PMID- 26799636 TI - Safety of long-term restrictive diets for peroxisomal disorders: vitamin and trace element status of patients treated for Adult Refsum Disease. AB - BACKGROUND: Adult Refsum's Disease (ARD) is caused by defects in the pathway for alpha-oxidation of phytanic acid (PA). Treatment involves restricting the dietary intake of phytanic acid by reducing the intake of dairy-derived fat. The adequacy of micronutrient intake in patients with ARD is unknown. METHODS: Patients established on the Chelsea low-PA diet had general diet macronutrients, vitamins and trace elements assessed using 7-day-weighed intakes and serial 24-h recalls. Intakes were compared with biochemical assessments of nutritional status for haematinics (ferritin), trace elements (copper, zinc, iron, selenium), water- (vitamin B6 , B12 and folate) and fat-soluble vitamins (A, D, E and K). RESULTS: Eleven subjects (four women, seven men) were studied. Body mass index was 27 +/- 5 kg/m(2) (range 19-38). All subjects had high sodium intakes (range 1873-4828 mg). Fat-soluble vitamin insufficiencies occurred in some individuals (vitamin A, n = 2; vitamin D, n = 6; vitamin E, n = 3; vitamin K, n = 10) but were not coincident. Vitamin B6 levels were normal or elevated (n = 6). Folate and 5 methyltetrahydrofolate concentrations were normal. Metabolic vitamin B12 insufficiency was suspected in four subjects based on elevated methylmalonic acid concentrations. Low copper and selenium intakes were noted in some subjects (n = 7, n = 2) but plasma levels were adequate. Iron, ferritin and zinc intakes and concentrations were normal. CONCLUSION: Subjects with ARD can be safely managed on the Chelsea low PA without routine micronutrient supplementation. Sodium intake should be monitored and reduced. Periodic nutritional screening may be necessary for fat-soluble vitamins, vitamin B12 , copper or selenium. PMID- 26799635 TI - Bioenergetic reprogramming of articular chondrocytes by exposure to exogenous and endogenous reactive oxygen species and its role in the anabolic response to low oxygen. AB - Monolayer culture is integral to many cell-based cartilage repair strategies, but chondrocytes lose regenerative potential with increasing duration in vitro. This coincides with elevated reactive oxygen species (ROS) levels and a bioenergetic transformation characterized by increasing mitochondrial function. This study investigates ROS as stimuli for bioenergetic reprogramming and the effect of antioxidants on the propensity of chondrocytes to regenerate a cartilaginous matrix. Articular chondrocytes were cultured in monolayer under a 2% O2 atmosphere. Oxidative stress was increased using 50 MUm H2 O2 or a 20% O2 culture atmosphere, or decreased using the antioxidant N-acetyl-cysteine (NAC). Mitochondrial function was characterized using 200 nm Mitotracker green and an oxygen biosensor. After two population doublings +/- NAC, chondrocytes were encapsulated in alginate beads (1 * 107 cells/ml) for an additional 10 days before DMB assay of glycosaminoglycan content. The beads were cultured under both 20% O2 and the more physiological 5% O2 condition. Chondrocytes expanded in 20% O2 exhibited elevated mitochondrial mass and functional capacity, which was partially mimicked by the exogenous ROS, H2 O2 . Oligomycin treatment revealed that the increased oxygen consumption was coupled to oxidative phosphorylation. NAC limited these markers of bioenergetic reprogramming during culture-expansion with no significant effect on subsequent GAG production under 20% O2 . However, NAC treatment in monolayer abolished the hypoxic induction of GAG in alginate beads. This supports the hypothesis of a causal relationship between exposure to ROS and acquired mitochondrial function in chondrocytes. Additionally, mitochondrial function may be required for the hypoxic induction of GAG synthesis by chondrocytes. (c) 2015 The Authors. Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons, Ltd. PMID- 26799638 TI - Melatonin receptor activation increases glutamatergic synaptic transmission in the rat medial lateral habenula. AB - Melatonin (MLT) is secreted from the pineal gland and mediates its physiological effects through activation of two G protein-coupled receptors, MT1 and MT2 . These receptors are expressed in several brain areas, including the habenular complex, a pair of nuclei that relay information from forebrain to midbrain and modulate a plethora of behaviors, including sleep, mood, and pain. However, so far, the precise mechanisms by which MLT control the function of habenula neurons remain unknown. Using whole cell recordings from male rat brain slices, we examined the effects of MLT on the excitability of medial lateral habenula (MLHb) neurons. We found that MLT had no significant effects on the intrinsic excitability of MLHb neurons, but profoundly increased the amplitude of glutamate mediated evoked excitatory post-synaptic currents (EPSC). The increase in strength of glutamate synapses onto MLHb neurons was mediated by an increase in glutamate release. The MLT-induced increase in glutamatergic synaptic transmission was blocked by the competitive MT1 /MT2 receptor antagonist luzindole (LUZ). These results unravel a potential cellular mechanism by which MLT receptor activation enhances the excitability of MLHb neurons. The MLT mediated control of glutamatergic inputs to the MLHb may play a key role in the modulation of various behaviors controlled by the habenular complex. PMID- 26799639 TI - Ultrathin Free-Standing Ternary-Alloy Nanosheets. AB - A synthesis strategy for the preparation of ultrathin free-standing ternary-alloy nanosheets is reported. Ultrathin Pd-Pt-Ag nanosheets with a thickness of approximately 3 nm were successfully prepared by co-reduction of the metal precursors in an appropriate molar ratio in the presence of CO. Both the presence of CO and the interplay between the constituent metals provide fine control over the anisotropic two-dimensional growth of the ternary-alloy nanostructure. The prepared Pd-Pt-Ag nanosheets were superior catalysts of ethanol electrooxidation owing to their specific structural and compositional characteristics. This approach will pave the way for the design of multicomponent 2D nanomaterials with unprecedented functions. PMID- 26799640 TI - Basic heart examination: feasibility study of first-trimester systematic simplified fetal echocardiography. AB - OBJECTIVE: First-trimester fetal cardiac screening examinations in low-risk populations should not have to meet the specifications required for high-risk populations. Our aim was to evaluate a simplified fetal echocardiographic ('basic heart') examination for early detection of severe congenital heart defects in a low-risk population. METHODS: This was a first-trimester national 'flash study', performed over a 2-week period. Each observer was requested to perform simplified echocardiography without modifying the time and methods deemed necessary for the routine first-trimester ultrasound examination, in fetuses with crown-rump length between 45 and 84 mm. This basic heart assessment used targeted cross-sections of the four-chamber view (4CV) and of the three vessels and trachea (3VT) view, using color and/or directional power Doppler. All examinations were then reviewed offline and scored for quality by a qualified expert. RESULTS: Sixty observers performed a total of 597 first-trimester ultrasound examinations, each performing an average of 10 (range, 1-26) procedures. Examinations were conducted transabdominally (79%; 472/597), transvaginally (3%; 17/597) or both (18%; 108/597). In 8% (45/597) of cases, the fetal back was anterior, in 18% (108/597) it was on the left side, in 63% (377/597) it was posterior and in 11% (67/597) it was on the right side. It became clear during scoring by the expert that, unlike the Herman quality score for nuchal translucency measurement, it was difficult to assess the quality of these images without taking into account normality of the heart itself. Analysis of scores showed that the 4CV was obtained successfully and was deemed normal in 86% (512/597) of the patients, in 7% (41/597) it was deemed technically infeasible and in 7% (44/597) it was deemed feasible but atypical, which may have been due to the presence of an abnormality or to poor quality of the image. The 3VT view was obtained successfully and was normal in 79% (472/597) of the patients, in 13% (78/597) it was technically infeasible and in 8% (47/597) it was deemed feasible but atypical. Both the 4CV and the 3VT view were obtained successfully and were normal in 73% (435/597) of patients. CONCLUSION: It is possible for a trained operator to perform simplified fetal echocardiography during the routine first-trimester ultrasound examination in a low-risk population. In most cases, our basic heart examination can be used to reassure parents or identify potential problems to be clarified as early as possible in the second trimester. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26799641 TI - Role of Carbon-Addition and Hydrogen-Migration Reactions in Soot Surface Growth. AB - Using density functional theory and master equation modeling, we have studied the kinetics of small unsaturated aliphatic molecules reacting with polycyclic aromatic hydrocarbon (PAH) molecules having a diradical character. We have found that these reactions follow the mechanism of carbon addition and hydrogen migration (CAHM) on both spin-triplet and open-shell singlet potential energy surfaces at a rate that is about ten times those of the hydrogen-abstraction carbon-addition (HACA) reactions at 1500 K in the fuel-rich postflame region. The results also show that the most active reaction sites are in the center of the zigzag edges of the PAHs. Furthermore, the reaction products are more likely to form straight rather than branched aliphatic side chains in the case of reacting with diacetylene. The computed rate constants are also found to be independent of pressure at conditions of interest in soot formation, and the activation barriers of the CAHM reactions are linearly correlated with the diradical characters. PMID- 26799644 TI - Dealing with patients facing a history of sexual abuse: A cross-sectional survey among Dutch general practitioners. AB - BACKGROUND: Sexual abuse (SA) is a common problem. As the primary confidant, the general practitioner (GP) has a valuable role in identifying a history of abuse, specifically with regard to the commonly performed pelvic examination for cervical cancer screening. OBJECTIVES: This study focused on GPs' practice patterns, knowledge, training need and barriers concerning asking patients about SA. Furthermore, it was investigated who performs the cervical smear within the practice and if SA is taken into consideration. METHODS: The authors constructed a 31-item questionnaire, which was sent to a group of 730 Dutch GPs in September 2012. RESULTS: The response rate was 49.3%. Half of the 357 responding GPs asked their patients about SA sometimes. The majority (76.2%) stated they had some knowledge of SA. The most important barriers for not asking were 'no angle or motive for asking' (81.6%), 'presence of third parties' (73.1%), and 'not enough training' (54.1%). In most practices (84.3%), the nurse practitioner (NP) was assigned to perform the cervical smears, of which 34.8% presumably never ask about SA in advance. Additional training was in need according to 68.6%. GPs desired a clinical practice guideline regarding the counselling of SA (83.5%). CONCLUSION: This study showed SA is an under-evaluated problem in general practice, yet GPs are motivated to improve knowledge and counselling skills. NPs perform most of the cervical smears, but the majority never or rarely asked about SA in advance. Educational training and a clinical guideline regarding SA would be appreciated and hence recommended. PMID- 26799646 TI - A New n = 4 Layered Ruddlesden-Popper Phase K(2.5)Bi(2.5)Ti4O13 Showing Stoichiometric Hydration. AB - A new bismuth-containing layered perovskite of the Ruddlesden-Popper type, K(2.5)Bi(2.5)Ti4O13, has been prepared by solid-state synthesis. It has been shown to hydrate to form stoichiometric K(2.5)Bi(2.5)Ti4O13.H2O. Diffraction data show that the structure consists of a quadruple-stacked (n = 4) perovskite layer, with potassium ions occupying the rock salt layer and its next-nearest A site. The hydrated sample was shown to remove the offset between stacked perovskite layers relative to the dehydrated sample. Computational methods show that the hydrated phase consists of intact H2O molecules in a vertical "pillared" arrangement bridging across the interlayer space. Rotations of H2O molecules about the c axis were evident in molecular dynamic calculations, which increased in rotation angle with increasing temperature. In situ diffraction data for the dehydrated phase point to a broad structural phase transition from orthorhombic to tetragonal at ~600 degrees C. The relative bismuth-rich composition in the perovskite block results in a higher transition temperature compared to related perovskite structures. Water makes a significant contribution to the dielectric constant, which disappears after dehydration. PMID- 26799649 TI - Fundamental insights into the electronic structure of zigzag MoS2 nanoribbons. AB - The structural and electronic properties of zigzag MoS2 nanoribbons are investigated using first-principles density functional theory. Our models are motivated by the experimental observations, in which both Mo edges are terminated by S atoms. Our calculations show that the edge can introduce some extra states into the energy gap, which lead nanoribbons to exhibit a metallic characteristic. Such extra states around the Fermi level are flat or dispersed. Through detailed analyses, we identify and discriminate them based on the major contributors. By applying an external transverse electric field, Eext the extra states around the Fermi level can shift apparently, especially for those attributed to Mo-edge atoms. It can be explained by the charge redistribution in the MoS2 nanoribbons due to Eext. In addition, the nanoribbon can be changed from metal to an n/p-type semiconductor according to different edge hydrogenation. After full edge hydrogenation, we observe a characteristic of anti-bonding orbitals between H and S atoms at the Mo-edge. Interestingly, the energy of anti-bonding orbitals and electric conductivity of nanoribbons can be tailored by Eext. The results suggest a strategy controlling the performance of MoS2 for hydrogen evolution. PMID- 26799651 TI - Correction: Network Structure and Biased Variance Estimation in Respondent Driven Sampling. PMID- 26799656 TI - Graphene-Immobilized fac-Re(bipy)(CO)3Cl for Syngas Generation from Carbon Dioxide. AB - We report the synthesis of fac-M(4-amino-bipy)(CO)3X (M = Mn and X = Br or M = Re and X = Cl, with bipy = 2,2'-bipyridine), their immobilization on graphene oxide (GrO) via diazonium grafting, and the use of Re-functionalized GrO for electrocatalytic syngas production. Infrared (IR) spectroscopy, X-ray absorption fine structure (XAFS) spectroscopy, and electrocatalysis indicated successful grafting of the Re catalyst onto GrO. Re-functionalized GrO was then deposited onto a glassy carbon electrode (GCE) for CO2 reduction. Investigation of the Re functionalized GCE for syngas production was performed in a CO2-saturated acetonitrile solution with 3.1 M H2O as the proton source and 0.1 M tetrabutylammonium hexafluorophosphate (TBAPF6) as the supporting electrolyte. Cyclic voltammetry (CV), controlled potential electrolysis (CPE), and gas chromatography (GC) were employed to determine its CO2-to-CO conversion performance. The Re catalyst shows a turnover frequency (TOF) for generating CO up to 4.44 s(-1) with a CO/H2 ratio of 7:5. PMID- 26799657 TI - The current treatment of Hepatitis C. AB - The development of potent antivirals able to directly block multiple step of viral lifecycle (DAAs) led to a revolution in HCV treatment. These compounds are associated with unprecedent high rates of SVR and can be administered orally, regardless of the severity of the associated liver disease, allowing treatment of large number of HCV infected patients. Three main classes of DAAs are currently available, NS3/4 inhibitors, NS5A inhibitors and NS5B inhibitors. They can be combined according to 2 different strategies, the use of a backbone drug with high barrier of resistance as the NS5B inhibitor sofosbuvir, with the addition of a second drug either NS3/4 or NS5A, or the use of more than 1 drug from different classes to simultaneously attack the virus at different sequence sites. DAAs can be administered for 12 or 24 weeks in the majority of patients, although attempts to reduce to 6-8 weeks the treatment duration in patients with baseline favorable characteristics are ongoing. Overall, SVR rates ensured by the currently approved combinations, are 90% or higher. Although cirrhotic patients and in particular patients with decompensated disease may represent a difficult to cure group, data from real life confirm evidence derived from phase III studies, showing improvement in biochemical parameters, even in such a special populations. We can expect, the number of patients with unmet medical needs will decline over time in the next 4 years. This review aims to discuss updated regimens by HCV genotype and to provide a brief summary of the coming strategies. PMID- 26799653 TI - Hepatitis B: treatment choice and monitoring for response and resistance. AB - Despite effective preventive primary prevention with vaccination, many people remain infected with hepatitis B virus (HBV) and suffer from its complications. Effective treatments such as interferon-based regimens and oral nucleoside/nucleotides have been developed over the last 30 years, but they are not perfect. Each of the treatments has its own merits, but none can eradicate HBV from the host. As a result, regular monitoring of the response during treatment and after treatment is required. The choice and monitoring of selected treatments, new potential therapeutic agents, and treatment options for drug resistance are discussed in this review. PMID- 26799661 TI - Veterans' Experiences using Complementary and Alternative Medicine for Posttraumatic Stress: A Qualitative Interpretive Meta-Synthesis. AB - Combat Veterans struggling with combat-related post(*)traumatic stress disorder and subthreshold symptoms often look outside the conventional behavioral health care system for treatment because standard care has not met their needs. This study utilized a qualitative interpretive metasynthesis to describe the lived experience of combat Veterans seeking complementary and alternative health therapies for posttraumatic stress symptoms. This research aimed to understand what attracts these Veterans to complementary and alternative medicine techniques and how they benefit from their experiences with nonconventional therapies. Findings suggest the need for further research into increasing access and eliminating disparities for Veterans seeking more integrative care. PMID- 26799660 TI - Iron Catalyzed Highly Enantioselective Epoxidation of Cyclic Aliphatic Enones with Aqueous H2O2. AB - An iron complex with a C1-symmetric tetradentate N-based ligand catalyzes the asymmetric epoxidation of cyclic enones and cyclohexene ketones with aqueous hydrogen peroxide, providing the corresponding epoxides in good to excellent yields and enantioselectivities (up to 99% yield, and 95% ee), under mild conditions and in short reaction times. Evidence is provided that reactions involve an electrophilic oxidant, and this element is employed in performing site selective epoxidation of enones containing two alkene sites. PMID- 26799655 TI - Neuroprotective effect of Arthrospira (Spirulina) platensis against kainic acid neuronal death. AB - Context Arthrospira (Spirulina) platensis (SP) is a cyanobacterium which has attracted attention because of its nutritional value and pharmacological properties. It was previously reported that SP reduces oxidative stress in the hippocampus and protects against damaging neurobehavioural effects of systemic kainic acid (KA). It is widely known that the systemic administration of KA induces neuronal damage, specifically in the CA3 hippocampal region. Objective The present study determines if the SP sub-chronic treatment has neuroprotective properties against KA. Materials and methods Male SW mice were treated with SP during 24 d, at doses of 0, 200, and 800 mg/kg, once daily, and with KA (35 mg/kg, ip) as a single dose on day 14. After the treatment, a histological analysis was performed and the number of atrophic neuronal cells in CA3 hippocampal region was quantified. Results Pretreatment with SP does not protect against seizures induced by KA. However, mortality in the SP 200 and the SP 800 groups was of 20%, while for the KA group, it was of 60%. A single KA ip administration produced a considerable neuronal damage, whereas both doses of SP sub-chronic treatment reduced the number of atrophic neurons in CA3 hippocampal region with respect to the KA group. Discussion The SP neurobehaviour improvement after KA systemic administration correlates with the capacity of SP to reduce KA neuronal death in CA3 hippocampal cells. This neuroprotection may be related to the antioxidant properties of SP. Conclusion SP reduces KA-neuronal death in CA3 hippocampal cells. PMID- 26799658 TI - Using In Vitro Immunomodulatory Properties of Lactic Acid Bacteria for Selection of Probiotics against Salmonella Infection in Broiler Chicks. AB - Poultry is known to be a major reservoir of Salmonella. The use of lactic acid bacteria has become one of successful strategies to control Salmonella in poultry. The purpose of this study was to select lactic acid bacteria strains by their in vitro immunomodulatory properties for potential use as probiotics against Salmonella infection in broiler chicks. Among 101 isolated lactic acid bacteria strains, 13 strains effectively survived under acidic (pH 2.5) and bile salt (ranging from 0.1% to 1.0%) conditions, effectively inhibited growth of 6 pathogens, and adhered to Caco-2 cells. However, their in vitro immunomodulatory activities differed significantly. Finally, three strains with higher in vitro immunomodulatory properties (Lactobacillus plantarum PZ01, Lactobacillus salivarius JM32 and Pediococcus acidilactici JH231) and three strains with lower in vitro immunomodulatory activities (Enterococcus faecium JS11, Lactobacillus salivarius JK22 and Lactobacillus salivarius JM2A1) were compared for their inhibitory effects on Salmonella adhesion and invasion to Caco-2 cells in vitro and their antimicrobial effects in vivo. The former three strains inhibited Salmonella adhesion and invasion to Caco-2 cells in vitro, reduced the number of Salmonella in intestinal content, spleen and liver, reduced the levels of lipopolysaccharide-induced TNF-alpha factor (LITAF), IL-1beta, IL-6 and IL-12 in serum and increased the level of IL-10 in serum during a challenge study in vivo more efficiently than the latter three strains. These results suggest that in vitro immunomodulatory activities could be used as additional parameters to select more effective probiotics as feed supplements for poultry. PMID- 26799659 TI - Peptidylarginine Deiminase 3 (PAD3) Is Upregulated by Prolactin Stimulation of CID-9 Cells and Expressed in the Lactating Mouse Mammary Gland. AB - Peptidylarginine deiminases (PADs) post-translationally convert arginine into neutral citrulline residues. Our past work shows that PADs are expressed in the canine and murine mammary glands; however, the mechanisms regulating PAD expression and the function of citrullination in the normal mammary gland are unclear. Therefore, the first objective herein was to investigate regulation of PAD expression in mammary epithelial cells. We first examined PAD levels in CID-9 cells, which were derived from the mammary gland of mid-pregnant mice. PAD3 expression is significantly higher than all other PAD isoforms and mediates protein citrullination in CID-9 cells. We next hypothesized that prolactin regulates PAD3 expression. To test this, CID-9 cells were stimulated with 5 MUg/mL of prolactin for 48 hours which significantly increases PAD3 mRNA and protein expression. Use of a JAK2 inhibitor and a dominant negative (DN)-STAT5 adenovirus indicate that prolactin stimulation of PAD3 expression is mediated by the JAK2/STAT5 signaling pathway in CID-9 cells. In addition, the human PAD3 gene promoter is prolactin responsive in CID-9 cells. Our second objective was to investigate the expression and activity of PAD3 in the lactating mouse mammary gland. PAD3 expression in the mammary gland is highest on lactation day 9 and coincident with citrullinated proteins such as histones. Use of the PAD3 specific inhibitor, Cl4-amidine, indicates that PAD3, in part, can citrullinate proteins in L9 mammary glands. Collectively, our results show that upregulation of PAD3 is mediated by prolactin induction of the JAK2/STAT5 signaling pathway, and that PAD3 appears to citrullinate proteins during lactation. PMID- 26799662 TI - Control of Wnt/beta-Catenin Signaling Pathway in Vivo via Light Responsive Capsules. AB - The possibility to remotely manipulate intracellular pathways in single cells is among the current goals of biomedicine, demanding new strategies to control cell function and reprogramming cell fate upon external triggering. Optogenetics is one approach in this direction, allowing specific cell stimulation by external illumination. Here, we developed optical switchers of an ancient and highly conserved system controlling a variety of developmental and adult processes in all metazoans, from Hydra to mammals, the Wnt/beta-catenin signaling pathway. An intracellular modulator of the Wnt pathway was enclosed into polyelectrolyte multilayer microcapsules engineered to include self-tracking (i.e., fluorescence labeling) and light mediated heating functionalities (i.e., plasmonic nanoparticles). Capsules were delivered in vivo to Hydra and NIR triggered drug release caused forced activation of the Wnt pathway. The possibility to remotely manipulate the Wnt pathway by optical switchers may be broadly translated to achieve spatiotemporal control of cell fate for new therapeutic strategies. PMID- 26799663 TI - Glomerular Immune Deposits Are Predictive of Poor Long-Term Outcome in Patients with Adult Biopsy-Proven Minimal Change Disease: A Cohort Study in Korea. AB - BACKGROUND AND OBJECTIVES: There has been little published information on risk factors for poor long-term outcome in adult biopsy-proven minimal change disease (MCD). METHODS: Data from sixty-three adult, biopsy-proven primary MCD patients treated at a tertiary university hospital between 2003 and 2013 were analyzed. Baseline clinical and pathologic factors were assessed for the associations with composite outcome of creatinine doubling, end stage renal disease, or all-cause mortality. RESULTS: During a median (interquartile) 5.0 (2.8-5.0) years, the composite outcome occurred in 11.1% (7/63) of patients. The rate of glomerular immune deposits was 23.8% (15/63). Patients with glomerular immune deposits showed a significantly lower urine protein creatinine ratio than those without deposits (P = 0.033). The rate of non-responders was significantly higher in patients with glomerular immune deposits than in those without deposits (P = 0.033). In patients with deposits, 26.7% (4/15) developed the composite outcome, while only 6.3% (3/48) developed the composite outcome among those without deposits (P = 0.049). In multivariate Cox proportional hazards regression analysis, the presence of glomerular immune deposits was the only factor associated with development of the composite outcome (hazard ratio: 2.310, 95% confidence interval: 1.031-98.579, P = 0.047). CONCLUSION: Glomerular immune deposits were associated with increased risk of a composite outcome in adult MCD patients. The higher rate of non-responders in patients with deposits might be related to the poor outcome. Future study is needed. PMID- 26799654 TI - Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia. AB - Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders. PMID- 26799664 TI - ATIC 347C>G gene polymorphism may be associated with methotrexate-induced adverse events in south Indian Tamil rheumatoid arthritis. AB - AIM: To find the association of ATIC 347C>G gene polymorphism with methotrexate (MTX) treatment response and MTX-induced adverse events in south Indian Tamil patients with rheumatoid arthritis. PATIENTS & METHODS: A total of 319 rheumatoid arthritis and 310 healthy controls were recruited for the study and ATIC 347C>G gene polymorphism was analyzed by PCR-RFLP method. RESULTS: The genotype and allele frequencies of ATIC 347 C>G SNP did not differ between good and nonresponders and hence this SNP was not found to be associated with MTX treatment response. However, the ATIC 347 GG genotype (p = 0.02; odds ratio [OR]: 4.46; 95% CI: 1.28-15.52) and mutant G allele was associated with MTX-induced gastrointestinal adverse events (p = 0.01; OR: 2.60; 95% CI: 1.27-5.35). CONCLUSION: ATIC 347C>G gene polymorphism may be associated with the development of MTX induced gastrointestinal adverse events. PMID- 26799665 TI - Clinical Studies Targeting Stroke and In-Hospital Cardiac Arrest. PMID- 26799666 TI - Collateral Damage and Critical Turning Points: Public Health Implications of HPV Vaccine News Coverage for Boys and Men in 2011. AB - In 2009, the Food and Drug Administration (FDA) officially expanded approval of the Gardasil vaccine to include human papillomavirus (HPV) vaccination for boys and men, and in 2011, the Centers for Disease Control and Prevention (CDC) issued a formal recommendation for routine vaccination for this population. Despite these efforts, HPV vaccination rates for boys and men continue to fall short of public health targets. While news was breaking about the benefits of the HPV vaccine for boys and men, public attention shifted as a result of political debates concerning the vaccine. This study examines a pivotal time period for public health in which the vaccine became officially recommended for boys and men and at the same time became the center of political controversies in the lead-up to the 2012 presidential campaign. The current study extends previous research and presents a content analysis of newspaper articles (N = 154) about the HPV vaccine for the year 2011. Results indicate that the lack of comprehensive coverage of HPV and the HPV vaccine found in previous studies continued in this year. Results shed light on key political events that may have functioned to overshadow the recommendation of the HPV vaccine for boys and men. The implications of this pattern of news coverage can inform public health efforts to address low rates of HPV vaccination uptake among boys and men in present day. PMID- 26799667 TI - TGF-beta1 and TGF-beta2 abundance in liver diseases of mice and men. AB - TGF-beta1 is a major player in chronic liver diseases promoting fibrogenesis and tumorigenesis through various mechanisms. The expression and function of TGF beta2 have not been investigated thoroughly in liver disease to date. In this paper, we provide evidence that TGF-beta2 expression correlates with fibrogenesis and liver cancer development.Using quantitative realtime PCR and ELISA, we show that TGF-beta2 mRNA expression and secretion increased in murine HSCs and hepatocytes over time in culture and were found in the human-derived HSC cell line LX-2. TGF-beta2 stimulation of the LX-2 cells led to upregulation of the TGF beta receptors 1, 2, and 3, whereas TGF-beta1 treatment did not alter or decrease their expression. In liver regeneration and fibrosis upon CCl4 challenge, the transient increase of TGF-beta2 expression was accompanied by TGF-beta1 and collagen expression. In bile duct ligation-induced fibrosis, TGF-beta2 upregulation correlated with fibrotic markers and was more prominent than TGF beta1 expression. Accordingly, MDR2-KO mice showed significant TGF-beta2 upregulation within 3 to 15 months but minor TGF-beta1 expression changes. In 5 of 8 hepatocellular carcinoma (HCC)/hepatoblastoma cell lines, relatively high TGF-beta2 expression and secretion were observed, with some cell lines even secreting more TGF-beta2 than TGF-beta1. TGF-beta2 was also upregulated in tumors of TGFalpha/cMyc and DEN-treated mice. The analysis of publically available microarray data of 13 human HCC collectives revealed considerable upregulation of TGF-beta2 as compared to normal liver.Our study demonstrates upregulation of TGF beta2 in liver disease and suggests TGF-beta2 as a promising therapeutic target for tackling fibrosis and HCC. PMID- 26799669 TI - Macrophage targeting contributes to the inhibitory effects of embelin on colitis associated cancer. AB - Macrophages are a major component of inflammatory and tumor microenvironment. We previously reported that embelin suppresses colitis-associated tumorigenesis. Here, the role of macrophage targeting in the anti-inflammatory and anti-tumor properties of embelin was investigated. By using colitis-associated cancer (CAC) model, we demonstrated that embelin significantly depleted colon macrophages by blocking their recruitment. Moreover, embelin attenuated M2-like polarization of macrophages within the tumor microenvironment and eliminated their tumor promoting functions during the development of CAC. Embelin potently inhibited NF kappaB signaling in macrophages and decreased the production of key pro inflammatory cytokines and tumorigenic factors involved in CAC, such as TNFalpha, IL-6 and COX-2. In addition, embelin directly reduced the polarization of M2 macrophages in vitro even in the presence of Th2 cytokines. These results suggested that targeting macrophages is, at least in part, responsible for the anti-tumor activity of embelin in CAC. Our observations strengthen the rationale for future validation of embelin in the prevention and treatment of CAC. PMID- 26799668 TI - miR-340 predicts glioblastoma survival and modulates key cancer hallmarks through down-regulation of NRAS. AB - Glioblastoma is the most common primary brain tumor in adults; with a survival rate of 12 months from diagnosis. However, a small subgroup of patients, termed long-term survivors (LTS), has a survival rate longer then 12-14 months. There is thus increasing interest in the identification of molecular signatures predicting glioblastoma prognosis and in how to improve the therapeutic approach. Here, we report miR-340 as prognostic tumor-suppressor microRNA for glioblastoma. We analyzed microRNA expression in > 500 glioblastoma patients and found that although miR-340 is strongly down-regulated in glioblastoma overall, it is up regulated in LTS patients compared to short-term survivors (STS). Indeed, miR-340 expression predicted better prognosis in glioblastoma patients. Coherently, overexpression of miR-340 in glioblastoma cells was found to produce a tumor suppressive activity. We identified NRAS mRNA as a critical, direct target of miR 340: in fact, miR-340 negatively influenced multiple aspects of glioblastoma tumorigenesis by down-regulating NRAS and downstream AKT and ERK pathways. Thus, we demonstrate that expression of miR-340 in glioblastoma is responsible for a strong tumor-suppressive effect in LTS patients by down-regulating NRAS. miR-340 may thus represent a novel marker for glioblastoma diagnosis and prognosis, and may be developed into a tool to improve treatment of glioblastoma. PMID- 26799671 TI - Revisiting the role of nanoparticles as modulators of drug resistance and metabolism in cancer. AB - INTRODUCTION: Drug resistance is the major obstacle impeding the efficacy of chemotherapeutic agents. Although numerous drug delivery techniques have been developed to combat drug resistance, their limitations of non-specific targeting and inconsistent bioavailability has led to the search of novel delivering strategies, such as nanoparticles. AREAS COVERED: Nanoparticles for anti-cancer drug delivery are microscopic preparations encapsulating a chemotherapeutic and a chemosensitizer into a rationally designed drug delivery vehicle. Nano-strategies directed against multi-drug resistance (MDR) can be categorized into those inhibiting the drug efflux pumps, those effective against the cellular factors of drug resistance, and the combinational based strategies. Here, we review the most recent literature to reposition nanoparticles as chemotherapeutics and inhibitors of MDR. EXPERT OPINION: Novelty in anti-cancer drug delivery has led to the formulation of chemotherapeutics and MDR inhibitors as nano-preparations, which are multi-functional and have better tumor cell-targeting effects. Their characteristics of size and surface attachments make them readily diffusible through the tumor vasculature and increase their retention time as well. With a better understanding of the molecular mechanisms of drug resistance, more potent and multi-targeted nano-preparations can be formulated in the near future. PMID- 26799670 TI - PP2A inhibition with LB100 enhances cisplatin cytotoxicity and overcomes cisplatin resistance in medulloblastoma cells. AB - The protein phosphatase 2A (PP2A) inhibitor, LB100, has been shown in pre clinical studies to be an effective chemo- and radio-sensitizer for treatment of various cancers. We investigated effects associated with LB100 treatment alone and in combination with cisplatin for medulloblastoma (MB) in vitro and in vivo in an intracranial xenograft model. We demonstrated that LB100 had a potent effect on MB cells. By itself, LB100 inhibited proliferation and induced significant apoptosis in a range of pediatric MB cell lines. It also attenuated MB cell migration, a pre-requirement for invasion. When used in combination, LB100 enhanced cisplatin-mediated cytotoxic effects. Cell viability in the presence of 1 uM cisplatin alone was 61% (DAOY), 100% (D341), and 58% (D283), but decreased with the addition of 2 MUM of LB100 to 26% (DAOY), 67% (D341), and 27% (D283), (p < 0.005). LB100 suppressed phosphorylation of the STAT3 protein and several STAT3 downstream targets. Also, LB100 directly increased cisplatin uptake and overcame cisplatin-resistance in vitro. Finally, LB100 exhibited potent in vivo anti-neoplastic activity in combination with cisplatin in an intracranial xenograft model. PMID- 26799675 TI - Protein Structural Memory Influences Ligand Binding Mode(s) and Unbinding Rates. AB - The binding of small molecules (e.g., natural ligands, metabolites, and drugs) to proteins governs most biochemical pathways and physiological processes. Here, we use molecular dynamics to investigate the unbinding of dimethyl sulfoxide (DMSO) from two distinct states of a small rotamase enzyme, the FK506-binding protein (FKBP). These states correspond to the FKBP protein relaxed with and without DMSO in the active site. Since the time scale of ligand unbinding (2-20 ns) is faster than protein relaxation (100 ns), a novel methodology is introduced to relax the protein without having to introduce an artificial constraint. The simulation results show that the unbinding time is an order of magnitude longer for dissociation from the DMSO-bound state (holo-relaxed). That is, the actual rate of unbinding depends on the state of the protein, with the protein having a long lived memory. The rate thus depends on the concentration of the ligand as the apo and holo states reflect low and high concentrations of DMSO, respectively. Moreover, there are multiple binding modes in the apo-relaxed state, while a single binding mode dominates the holo-relaxed state in which DMSO acts as hydrogen bond acceptor from the backbone NH of Ile56, as in the crystal structure of the DMSO/FKBP complex. The solvent relaxes very fast (~1 ns) close to the NH of Ile56 and with the same time scale of the protein far away from the active site. These results have implications for high-throughput docking, which makes use of a rigid structure of the protein target. PMID- 26799673 TI - Toxicological and ecotoxicological risk-based prioritization of pharmaceuticals in the natural environment. AB - Approximately 1500 active pharmaceutical ingredients are currently in use; however, the environmental occurrence and impacts of only a small proportion of these have been investigated. Recognizing that it would be impractical to monitor and assess all pharmaceuticals that are in use, several previous studies have proposed the use of prioritization approaches to identify substances of most concern so that resources can be focused on these. All of these previous approaches suffer from limitations. In the present study, the authors draw on experience from previous prioritization exercises and present a holistic approach for prioritizing pharmaceuticals in the environment in terms of risks to aquatic and soil organisms, avian and mammalian wildlife, and humans. The approach considers both apical ecotoxicological endpoints as well as potential nonapical effects related to the therapeutic mode of action. Application of the approach is illustrated for 146 active pharmaceuticals that are used either in the community or in hospital settings in the United Kingdom. Using the approach, 16 compounds were identified as a potential priority. These substances include compounds belonging to the antibiotic, antidepressant, anti-inflammatory, antidiabetic, antiobesity, and estrogen classes as well as associated metabolites. In the future, the prioritization approach should be applied more broadly around the different regions of the world. Environ Toxicol Chem 2016;35:1550-1559. (c) 2016 SETAC. PMID- 26799677 TI - Aluminum Nanocrystals as a Plasmonic Photocatalyst for Hydrogen Dissociation. AB - Hydrogen dissociation is a critical step in many hydrogenation reactions central to industrial chemical production and pollutant removal. This step typically utilizes the favorable band structure of precious metal catalysts like platinum and palladium to achieve high efficiency under mild conditions. Here we demonstrate that aluminum nanocrystals (Al NCs), when illuminated, can be used as a photocatalyst for hydrogen dissociation at room temperature and atmospheric pressure, despite the high activation barrier toward hydrogen adsorption and dissociation. We show that hot electron transfer from Al NCs to the antibonding orbitals of hydrogen molecules facilitates their dissociation. Hot electrons generated from surface plasmon decay and from direct photoexcitation of the interband transitions of Al both contribute to this process. Our results pave the way for the use of aluminum, an earth-abundant, nonprecious metal, for photocatalysis. PMID- 26799678 TI - Therapeutic substitutions in the midst of new technology diffusion: The case of treatment for localized prostate cancer. AB - Robotic surgical systems have become increasingly popular worldwide. Robotic assisted radical prostatectomies have been widely adopted in the treatment of localized prostate cancer, replacing the conventional open surgeries. However, it is not clear whether this was achieved by substitution within the same treatment type (i.e., replacing open surgeries with robotic-assisted surgeries) or substitution across treatment types (i.e., expanding the proportion of patients receiving surgery while crowding out other forms of treatment for localized prostate cancer). Given the large number of patients undergoing these procedures each year, it is important to study the impact of the fast diffusion of robotic surgical systems on the overall treatment pattern of localized prostate cancer. We addressed this question using state-level cancer epidemiology data (256 observations) extracted from 2002 to 2010 National Cancer Database, and supply side variables (e.g. density of robotic surgical systems, urologists) obtained from Area Resource File as well as investor presentations posted at the website of the manufacturer of robotic surgical systems. Recognizing that the purchase decision of robotic systems is potentially endogenous, we used an optimal instrumental variables panel estimation method to examine the impact while taking into account of the panel structure and the potential endogeneity of the density of robotic surgical systems and its quadratic term. We found that the density of robotic systems at state-level had a significantly positive impact on the rate of surgery and a significantly negative impact on the rate of radiation therapy. Further, our age-stratified analysis showed that the increase in surgery rate was most pronounced in the younger population. In conclusion, our findings suggest that part of the increase in the rate of surgery was driven by substitution across treatment types with a large proportion originating from the younger population. PMID- 26799679 TI - Modulation of hand motor-related area during motor imagery and motor execution before and after middle 2/5 of the MS6 line scalp acupuncture stimulation: An fMRI study. AB - Scalp acupuncture (SA) combines the concept of cerebral cortex organization with the principles of acupuncture. The SA stimulates sections of the cerebral cortex. We studied the functional modulation of the left hand sensorimotor area induced by SA in order to investigate the specificity of the SA-related functional effects of the middle 2/5 of the MS6 line of the left side, which corresponds to the upper limb motor segment of the primary motor area. To this purpose, we compared the pre- and post-SA functional activation patterns during an implicit motor imagery task (handedness decision in which participants simulated rotational hand movements) and an explicit manual motor execution task. Feet and mouth movements, and the fMRI changes in their respective representations were used as control conditions. Only SA on the hand area of the left side (as compared to the mouth and the foot representations which were used as control conditions) exerted a release effect on the right hand area. In addition, an increased activation of the superior parietal lobe was seen, which is involved in movement control and planning. Taken together, these preliminary findings may shed light on the SA effects and confirm a prolonged effect of SA even after cessation of needling stimulation. PMID- 26799680 TI - Adult developmental trajectories of pseudoneglect in the tactile, visual and auditory modalities and the influence of starting position and stimulus length. AB - Pseudoneglect is a tendency to pay more attention to the left side of space, typically demonstrated on tasks like visuo-spatial line bisection, tactile rod bisection and the mental representation of numbers. The developmental trajectory of this bias on these three tasks is not fully understood. In the current study younger participants aged between 18 and 40 years of age and older participants aged between 55 and 90 years conducted three spatial tasks: (1) visuospatial line bisection - participants were asked to bisect visually presented lines of different lengths at the perceived midpoint; (2) touch-driven tactile rod bisection in the absence of vision - participants were asked to feel the length of a wooden rod with their index finger and bisect the rod at the perceived centre; and (3) mental number line bisection in the absence of vision - participants were asked to listen to a pair of numbers and respond with the numerical midpoint between the pair. The results showed that both younger and older participants demonstrated pseudoneglect (leftward biases) in the visual, tactile and mental number line tasks and that the magnitude of pseudoneglect for each group was influenced by physical or mentally represented starting side (start left versus start right) and stimulus length. We provide an exploration of pseudoneglect in younger and older adults in different tasks that vary in the degree to which mental representations are accessed and argue that pseudoneglect is a result of a right hemisphere attentional orienting process that is retained throughout adulthood. Our results indicate that, contrary to some current models of cognitive ageing, asymmetrical patterns of hemispheric activity may occur in older age. PMID- 26799681 TI - Foodomics imaging by mass spectrometry and magnetic resonance. AB - This work explores the use of advanced imaging MS (IMS) and magnetic resonance imaging (MRI) techniques in food science and nutrition to evaluate food sensory characteristics, nutritional value and health benefits. Determining the chemical content and applying imaging tools to food metabolomics offer detailed information about food quality, safety, processing, storage and authenticity assessment. IMS and MRI are powerful analytical systems with an excellent capability for mapping the distribution of many molecules, and recent advances in these platforms are reviewed and discussed, showing the great potential of these techniques for small molecule-based food metabolomics research. PMID- 26799683 TI - Catheter Ablation for "Lone" Atrial Fibrillation: Efficacy and Predictors of Recurrence. AB - BACKGROUND: Atrial fibrillation in otherwise healthy young patients has been termed "lone" atrial fibrillation (AF). The best treatment choice is still under discussion. The aim of this study was to report on efficacy and safety of catheter ablation. METHODS: Among 855 patients referred to our center between 2011 and 2013, 76 (9%) met the diagnostic criteria for lone AF (mean age 45 +/- 8 years; mean LA diameter 37 +/- 4 mm; paroxysmal AF 82%; persistent AF 18%). The primary endpoint was freedom from any atrial tachycardia after the first ablation; the secondary endpoint was freedom from any atrial tachycardia after the last ablation procedure without antiarrhythmic drugs. RESULTS: The primary endpoint occurred in 56 patients (74%) after a mean follow-up time of 444 +/- 344 days. The secondary endpoint occurred in 73 patients (96%) after a mean of 1.3 ablations/patient during a follow-up time of 459 +/- 366 days. The risk of AF recurrence was not influenced by AF duration or by the type of AF (paroxysmal versus persistent). In a multivariate regression analysis smoking (P = 0.001), first degree atrioventricular block (P = 0.001), and early (< 3 months) AF recurrence (P = 0.001) were independently associated with a higher risk of AF recurrence. Major peri-procedural adverse events did not occur. CONCLUSIONS: Catheter ablation in young healthy patients is highly effective and safe. The outcomes are maintained during long-term follow-up irrespective of preoperative AF duration. Patients with AF recurrence were more likely to smoke, have first degree AV block and early AF recurrence. PMID- 26799685 TI - Bayesian methods of confidence interval construction for the population attributable risk from cross-sectional studies. AB - Population attributable risk measures the public health impact of the removal of a risk factor. To apply this concept to epidemiological data, the calculation of a confidence interval to quantify the uncertainty in the estimate is desirable. However, because perhaps of the confusion surrounding the attributable risk measures, there is no standard confidence interval or variance formula given in the literature. In this paper, we implement a fully Bayesian approach to confidence interval construction of the population attributable risk for cross sectional studies. We show that, in comparison with a number of standard Frequentist methods for constructing confidence intervals (i.e. delta, jackknife and bootstrap methods), the Bayesian approach is superior in terms of percent coverage in all except a few cases. This paper also explores the effect of the chosen prior on the coverage and provides alternatives for particular situations. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26799684 TI - Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity. AB - Eosinophilic esophagitis (EoE) is a chronic disease characterized clinically by symptoms of esophageal dysfunction and histologically by eosinophil-predominant inflammation. EoE is frequently associated with concomitant atopic diseases and immunoglobulin E (IgE) sensitization to food allergens in children as well as to aeroallergens and cross-reactive plant allergen components in adults. Patients with EoE respond well to elemental and empirical food elimination diets. Recent research has, however, indicated that the pathogenesis of EoE is distinct from IgE-mediated food allergy. In this review, we discuss the individual roles of epithelial barrier defects, dysregulated innate and adaptive immune responses, and of microbiota in the pathogenesis of EoE. Although food has been recognized as a trigger factor of EoE, the mechanism by which it initiates or facilitates eosinophilic inflammation appears to be largely independent of IgE and needs to be further investigated. Understanding the pathogenic role of food in EoE is a prerequisite for the development of specific diagnostic tools and targeted therapeutic procedures. PMID- 26799687 TI - Promoting an Alternative to Traditional Nursing Home Care: Evaluating the Green House Small Home Model. An Introduction from the Funders and the Green House Project. PMID- 26799689 TI - Differences in beta-cell function and insulin secretion in Black vs. White obese adolescents: do incretin hormones play a role? AB - Black youth are at higher risk for type 2 diabetes (T2D) than their White peers. Previously we demonstrated that for the same degree of insulin sensitivity, Black youth have an upregulated beta-cell function and insulin hypersecretion, in response to intravenous (iv) glucose, compared with Whites. To investigate if the same holds true during an oral glucose challenge and because of the important role of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in augmenting insulin secretion, we examined beta-cell function and incretin hormones in 85 Black and 78 White obese adolescents, with normal glucose tolerance (NGT), during a 2-h oral glucose tolerance test (OGTT) with mathematical modeling of plasma glucose and C-peptide concentrations to assess beta-cell glucose sensitivity (betaCGS), rate sensitivity, potentiation factor, and insulin sensitivity. Incretin, pancreatic polypeptide, and glucagon concentrations were measured during the OGTT. Black obese youth had a heightened early insulin secretion together with significantly greater betaCGS, rate sensitivity, and potentiation factor compared with Whites, with no differences in incretin and glucagon concentrations. Basal and stimulated insulin clearance was lower (p = 0.001) in Black vs. White youth. In conclusion, during an OGTT Black obese youth with NGT demonstrate a pronounced early insulin secretion jointly with heightened beta-cell glucose sensitivity, rate sensitivity, and potentiation factor. These racial disparities in beta-cell function and the pathophysiological components of T2D are unlikely to be attributed to incretin hormones and remain to be investigated further to explain the metabolic basis for the enhanced risk of T2D in back youth. PMID- 26799690 TI - Prevalence of mild cognitive impairment and dementia in older non-western immigrants in the Netherlands: a cross-sectional study. AB - OBJECTIVE: In the Netherlands, persons of Turkish, Moroccan and Surinamese descent form the largest groups of non-western immigrants. A high prevalence of mild cognitive impairment (MCI) and dementia has been described in immigrant populations in the United States of America and the United Kingdom. We determined the prevalence of MCI and dementia in older community-dwelling adults from the largest non-western immigrant groups in the Netherlands. METHODS: Participants, aged 55 years and older, of Turkish, Moroccan (Arabic or Berber), Surinamese (Creole or Hindustani) or Dutch descent were recruited via their general practitioners. Cognitive deficits were assessed using the Cross-Cultural Dementia screening instrument, which was validated in poorly educated people from different cultures. Differences in prevalence rates of MCI and dementia between the immigrant groups and a native Dutch group were analysed using chi-square tests. RESULTS: We included 2254 participants. Their mean age was 65.0 years (standard deviation, 7.5), and 44.4% were male. The prevalence of MCI was 13.0% in Turkish, 10.1% in Moroccan-Arabic, 9.4% in Moroccan-Berber and 11.9% in Surinamese-Hindustani participants, compared to 5.9% in Surinamese-Creoles and 3.3% in native Dutch. The prevalence of dementia was 14.8% in Turkish, 12.2% in Moroccan Arabic, 11.3% in Moroccan Berber and 12.6% in Surinamese-Hindustani participants, compared to 4.0% in Surinamese-Creoles and 3.5% in native Dutch. CONCLUSIONS: MCI and dementia were three to four times more prevalent in the majority of non-western immigrant groups when compared to the native Dutch population. These differences are important for planning and improving healthcare facilities. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26799694 TI - Arm-cycling sprints induce neuromuscular fatigue of the elbow flexors and alter corticospinal excitability of the biceps brachii. AB - We examined the effects of arm-cycling sprints on maximal voluntary elbow flexion and corticospinal excitability of the biceps brachii. Recreationally trained athletes performed ten 10-s arm-cycling sprints interspersed with 150 s of rest in 2 separate experiments. In experiment A (n = 12), maximal voluntary contraction (MVC) force of the elbow flexors was measured at pre-sprint 1, post sprint 5, and post-sprint 10. Participants received electrical motor point stimulation during and following the elbow flexor MVCs to estimate voluntary activation (VA). In experiment B (n = 7 participants from experiment A), supraspinal and spinal excitability of the biceps brachii were measured via transcranial magnetic and transmastoid electrical stimulation that produced motor evoked potentials (MEPs) and cervicomedullary motor evoked potentials (CMEPs), respectively, during a 5% isometric MVC at pre-sprint 1, post-sprint 1, post sprint 5, and post-sprint 10. In experiment A, mean power output, MVC force, potentiated twitch force, and VA decreased 13.1% (p < 0.001), 8.7% (p = 0.036), 27.6% (p = 0.003), and 5.6% (p = 0.037), respectively, from pre-sprint 1 to post sprint 10. In experiment B, (i) MEPs decreased 42.1% (p = 0.002) from pre-sprint 1 to post-sprint 5 and increased 40.1% (p = 0.038) from post-sprint 5 to post sprint 10 and (ii) CMEPs increased 28.5% (p = 0.045) from post-sprint 1 to post sprint 10. Overall, arm-cycling sprints caused neuromuscular fatigue of the elbow flexors, which corresponded with decreased supraspinal and increased spinal excitability of the biceps brachii. The different post-sprint effects on supraspinal and spinal excitability may illustrate an inhibitory effect on supraspinal drive that reduces motor output and, therefore, decreases arm-cycling sprint performance. PMID- 26799692 TI - Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1 infected patients without cirrhosis: OPTIMIST-1, a phase 3, randomized study. AB - Effective antiviral therapy is essential for achieving sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients. The phase 2 COSMOS study reported high SVR rates in treatment-naive and prior null-responder HCV genotype (GT) 1-infected patients receiving simeprevir+sofosbuvir+/-ribavirin for 12 or 24 weeks. OPTIMIST-1 (NCT02114177) was a multicenter, randomized, open label study assessing the efficacy and safety of 12 and 8 weeks of simeprevir+sofosbuvir in HCV GT1-infected treatment-naive and treatment experienced patients without cirrhosis. Patients were randomly assigned (1:1; stratified by HCV GT/subtype and presence or absence of NS3 Q80K polymorphism [GT1b, GT1a with Q80K, GT1a without Q80K]), prior HCV treatment history, and IL28B GT [CC, non-CC]) to simeprevir 150 mg once daily+sofosbuvir 400 mg once daily for 12 or 8 weeks. The primary efficacy endpoint was SVR rate 12 weeks after end of treatment (SVR12). Superiority in SVR12 was assessed for simeprevir+sofosbuvir at 12 and 8 weeks versus a composite historical control SVR rate. Enrolled were 310 patients, who were randomized and received treatment (n = 155 in each arm). SVR12 with simeprevir+sofosbuvir for 12 weeks (97% [150/155; 95% confidence interval 94%-100%]) was superior to the historical control (87%). SVR12 with simeprevir+sofosbuvir for 8 weeks (83% [128/155; 95% confidence interval 76-89%]) was not superior to the historical control (83%). The most frequent adverse events were nausea, headache, and fatigue (12-week arm: 15% [23/155], 14% [22/155], and 12% [19/155]; 8-week arm: 9% [14/155], 17% [26/155], and 15% [23/155], respectively). No patients discontinued treatment due to an adverse event. One (1%, 12-week arm) and three (2%, 8-week arm) patients experienced a serious adverse event (all unrelated to study treatment). CONCLUSION: Simeprevir+sofosbuvir for 12 weeks is highly effective in the treatment of HCV GT1-infected patients without cirrhosis, including those with Q80K. (Hepatology 2016;64:370-380). PMID- 26799695 TI - Effects of age and hindlimb immobilization and remobilization on fast troponin T precursor mRNA alternative splicing in rat gastrocnemius muscle. AB - Fast skeletal muscle troponin T (TNNT3) is an important component of the skeletal muscle contractile machinery. The precursor mRNA (pre-mRNA) encoding TNNT3 is alternatively spliced, and changes in the pattern of TNNT3 splice form expression are associated with alterations in thin-filament calcium sensitivity and force production during muscle contraction and thereby regulate muscle function. Interestingly, during aging, the muscle force/cross-sectional area is reduced, suggesting that loss of mass does not completely account for the impaired muscle function that develops during the aging process. Therefore, in this study, we tested the hypothesis that age and changes in muscle loading are associated with alterations in Tnnt3 alternative splicing in the rat gastrocnemius muscle. We found that the relative abundance of several Tnnt3 splice forms varied significantly with age among 2-, 9-, and 18-month-old rats and that the pattern correlated with changes in body mass rather than muscle mass. Hindlimb immobilization for 7 days resulted in dramatic alterations in splice form relative abundance such that the pattern was similar to that observed in lighter animals. Remobilization for 7 days restored the splicing pattern toward that observed in the nonimmobilized limb, even though muscle mass had not yet begun to recover. In conclusion, the results suggest that Tnnt3 pre-mRNA alternative splicing is modulated rapidly (i.e., within days) in response to changes in the load placed on the muscle. Moreover, the results show that restoration of Tnnt3 alternative splicing to control patterns is initiated prior to an increase in muscle mass. PMID- 26799696 TI - Social learning theory and public perception of GMOs: What Blancke et al. (2015) and other plant biotechnologists are missing. AB - There exists a wide chasm between public opinion and scientific evidence on the safety of genetically engineered food, herein referred to as GMOs. Plant biotechnologists give credit to a small community of activists negatively influencing individual minds on this issue, but this approach neglects other social contexts in which such cognition operates. The author argues here that current public opinion on GMOs is a manifestation of the constant interaction between environmental, behavioral, and cognitive influences on this issue. In order to sway public opinion and be consistent with social learning theory, biotechnology advocates and plant scientists will need to move beyond their recognized expertise in order to rework the argument for GMOs in the modern-day food supply, one that wholly embraces an individual-level framing of the debate, tantamount to other successful professional trends like patient-centered medicine. (c) 2016 Society of Chemical Industry. PMID- 26799697 TI - Validation of the revised International Prognostic Score of Thrombosis for Essential Thrombocythemia (IPSET-thrombosis) in 585 Mayo Clinic patients. AB - The primary objective of treatment in essential thrombocythemia (ET) is to prevent thromboembolic complications. In this regard, advanced age and thrombosis history have long distinguished "low" from "high" risk patients. More recently, JAK2V617F and cardiovascular (CV) risk factors were identified as additional modifiers, leading to the development of a 3-tiered International Prognostic Score of Thrombosis for ET (IPSET-thrombosis): "low," "intermediate," and "high". The international data set used to develop IPSET-thrombosis was recently re analyzed in order to quantify the additional pro-thrombotic effect of JAK2V617F and CV risk factors in specific risk subcategories. The revised IPSET-thrombosis identified four risk categories based on three adverse variables (thrombosis history, age >60 years and JAK2V617F): very low (no adverse features), low (presence of JAK2V617F), intermediate (age >60 years) and high (presence of thrombosis history or presence of both advanced age and JAK2V617F). In this study of 585 patients with ET (median age 68 years; 61% female), we validated the revised IPSET-thrombosis by confirming significant differences in thrombosis risk between "very low" and "low" (HR 2.4, 95% CI 1.1 - 5.3) and between "intermediate" and "high" (HR 2.3, 95% CI 1.1 - 5.2) risk patients. Furthermore, in multivariable analysis, only JAK2V617F (HR=1.8, CI= 1.07 - 2.94) and history of thrombosis (HR=2.1, CI= 1.20 - 3.58) were independently predictive of future thrombotic events. The revised IPSET-thrombosis needs confirmation in prospective studies, especially in terms of risk-adapted therapy that includes the need for aspirin therapy in very low risk, twice-daily aspirin therapy for low risk and cytoreductive therapy for low or intermediate risk patients. PMID- 26799698 TI - Sub-mammary injection of ropivacaine resulting in severe toxicity with seizures. PMID- 26799699 TI - Variants in TERT influencing telomere length are associated with paranoid schizophrenia risk. AB - Schizophrenia is one of the most severe psychiatric disorders, with a high heritability of up to 80%. Several studies have reported telomere dysfunction in schizophrenia, and common variants in the telomerase reverse transcriptase (TERT) gene. TERT is a key component of the telomerase complex that maintains telomere length by addition of telomere repeats to telomere ends, and has repeatedly shown association with mean lymphocyte telomere length (LTL). Thus, we hypothesized that TERT may be a novel susceptibility gene for schizophrenia. Using a Taqman protocol, we genotyped eight tag SNPs from the TERT locus in 1,072 patients with paranoid schizophrenia and 1,284 control subjects from a Chinese Han population. We also measured mean LTL in 98 cases and 109 controls using a quantitative PCR based technique. Chi-square tests showed that two SNPs, rs2075786 (P = 0.0009, OR = 0.76, 95%CI = 0.65-0.90) and rs4975605 (P = 0.0026, OR = 0.73, 95%CI = 0.60 0.90), were associated with a protective effect, while rs10069690 was associated with risk of paranoid schizophrenia (P = 0.0044, OR = 1.23, 95%CI = 1.07-1.42). Additionally, the rs2736118-rs2075786 haplotype showed significant association with paranoid schizophrenia (P = 0.0013). Moreover, mean LTL correlated with rs2075786 genotypes was significantly shorter in the patient group than the control group. The present results suggest that the TERT gene may be a novel candidate involved in the development of paranoid schizophrenia. PMID- 26799700 TI - Estimating treatment effect in a proportional hazards model in randomized clinical trials with all-or-nothing compliance. AB - We consider methods for estimating the treatment effect and/or the covariate by treatment interaction effect in a randomized clinical trial under noncompliance with time-to-event outcome. As in Cuzick et al. (2007), assuming that the patient population consists of three (possibly latent) subgroups based on treatment preference: the ambivalent group, the insisters, and the refusers, we estimate the effects among the ambivalent group. The parameters have causal interpretations under standard assumptions. The article contains two main contributions. First, we propose a weighted per-protocol (Wtd PP) estimator through incorporating time-varying weights in a proportional hazards model. In the second part of the article, under the model considered in Cuzick et al. (2007), we propose an EM algorithm to maximize a full likelihood (FL) as well as the pseudo likelihood (PL) considered in Cuzick et al. (2007). The E step of the algorithm involves computing the conditional expectation of a linear function of the latent membership, and the main advantage of the EM algorithm is that the risk parameters can be updated by fitting a weighted Cox model using standard software and the baseline hazard can be updated using closed-form solutions. Simulations show that the EM algorithm is computationally much more efficient than directly maximizing the observed likelihood. The main advantage of the Wtd PP approach is that it is more robust to model misspecifications among the insisters and refusers since the outcome model does not impose distributional assumptions among these two groups. PMID- 26799702 TI - FANCA Gene Mutations with 8 Novel Molecular Changes in Indian Fanconi Anemia Patients. AB - Fanconi anemia (FA), a rare heterogeneous genetic disorder, is known to be associated with 19 genes and a spectrum of clinical features. We studied FANCA molecular changes in 34 unrelated and 2 siblings of Indian patients with FA and have identified 26 different molecular changes of FANCA gene, of which 8 were novel mutations (a small deletion c.2500delC, 4 non-sense mutations c.2182C>T, c.2630C>G, c.3677C>G, c.3189G>A; and 3 missense mutations; c.1273G>C, c.3679 G>C, and c.3992 T>C). Among these only 16 patients could be assigned FA-A complementation group, because we could not confirm single exon deletions detected by MLPA or cDNA amplification by secondary confirmation method and due to presence of heterozygous non-pathogenic variations or heterozygous pathogenic mutations. An effective molecular screening strategy should be developed for confirmation of these mutations and determining the breakpoints for single exon deletions. PMID- 26799703 TI - Electronic Characterization of Au/DNA/ITO Metal-Semiconductor-Metal Diode and Its Application as a Radiation Sensor. AB - Deoxyribonucleic acid or DNA molecules expressed as double-stranded (DSS) negatively charged polymer plays a significant role in electronic states of metal/silicon semiconductor structures. Electrical parameters of an Au/DNA/ITO device prepared using self-assembly method was studied by using current-voltage (I-V) characteristic measurements under alpha bombardment at room temperature. The results were analyzed using conventional thermionic emission model, Cheung and Cheung's method and Norde's technique to estimate the barrier height, ideality factor, series resistance and Richardson constant of the Au/DNA/ITO structure. Besides demonstrating a strongly rectifying (diode) characteristic, it was also observed that orderly fluctuations occur in various electrical parameters of the Schottky structure. Increasing alpha radiation effectively influences the series resistance, while the barrier height, ideality factor and interface state density parameters respond linearly. Barrier height determined from I-V measurements were calculated at 0.7284 eV for non-radiated, increasing to about 0.7883 eV in 0.036 Gy showing an increase for all doses. We also demonstrate the hypersensitivity phenomena effect by studying the relationship between the series resistance for the three methods, the ideality factor and low dose radiation. Based on the results, sensitive alpha particle detectors can be realized using Au/DNA/ITO Schottky junction sensor. PMID- 26799704 TI - COMPUTED TOMOGRAPHIC APPEARANCE OF MELANOMAS IN THE EQUINE HEAD: 13 CASES. AB - Melanomas are one of the most common neoplasms in the horse and are frequently found in the head region. There is a genetic predisposition in horses with a gray hair coat. Computed tomography (CT) is frequently used in referral practice to evaluate the equine head but there are few reports describing the CT appearance of melanomas in this location. The aim of this retrospective, case series study was to describe characteristics in a group of horses with confirmed disease. Case records from two referral hospitals were reviewed, and 13 horses were identified that had undergone CT of the head, with a diagnosis of melanoma based on cytology, histopathology, or visual assessment of black (melanotic) tissue. A median of 11 melanomas was identified per horse (range 3-60), with a total of 216 masses. Melanomas were found most frequently in the parotid salivary gland, guttural pouches, surrounding the larynx and pharynx and adjacent to the hyoid apparatus. In noncontrast CT images, all melanomas were hyperattenuating (median; 113.5 Hounsfield units (HU), IQR; 26 HU) compared to masseter musculature (median; 69 HU, IQR; 5.5 HU). Fifty-six (25.9%) masses were partially mineralized and 41 (19.4%) included hypoattenuating areas. Histopathological assessment of these melanomas suggested that the hyperattenuation identified was most likely a result of abundant intracytoplasmic melanin pigment. Melanomas of the equine head appeared to have consistent CT features that aided detection of mass lesions and their distribution, although histopathological analysis or visual confirmation should still be obtained for definitive diagnosis. PMID- 26799705 TI - Effect of Storage on the Physico-Chemical and Antioxidant Properties of Strawberry and Kiwi Leathers. AB - Strawberry and kiwi leathers were used to develop a new healthy and preservative free fruit snack for new markets. Fruit puree was dehydrated at 60 degrees C for 20 h and subjected to accelerated storage. Soluble solids, titratable acidity, pH, water activity (aw ), total phenolic (TP), antioxidant activity (AOA) and capacity (ORAC), and color change (browning index) were measured in leathers, cooked, and fresh purees. An untrained panel was used to evaluate consumer acceptability. Soluble solids of fresh purees were 11.24 to 13.04 degrees Brix, whereas pH was 3.46 to 3.39. Leathers presented an aw of 0.59 to 0.67, and a moisture content of 21 kg water/100 kg. BI decreased in both leathers over accelerated storage period. TP and AOA were higher (P <= 0.05) in strawberry formulations. ORAC decreased 57% in strawberry and 65% in kiwi leathers when compared to fruit puree. TP and AOA increased in strawberries during storage. Strawberry and Kiwi leathers may be a feasible new, natural, high antioxidant, and healthy snack for the Chilean and other world markets, such as Europe, particularly the strawberry leather, which was preferred by untrained panelists. PMID- 26799708 TI - Involvement of the orexin/hypocretin system in the pharmacological effects induced by Delta(9) -tetrahydrocannabinol. AB - BACKGROUND AND PURPOSE: Anatomical, biochemical and pharmacological evidence suggest the existence of a crosstalk between the orexinergic and endocannabinoid systems. While the orexin receptor 1 (OX1 receptor) modulates the reinforcing properties of cannabinoids, the participation of orexins in the acute pharmacological effects of Delta(9) -tetrahydrocannabinol (THC) remains unexplored. EXPERIMENTAL APPROACH: We assessed the possible role of orexins in THC-induced hypolocomotion, hypothermia, antinociception, anxiolytic- and anxiogenic-like effects and memory impairment. Selective OX1 and OX2 receptor antagonists and OX1 knockout (KO) mice as well as prepro-orexin (PPO) KO mice were used as pharmacological and genetic approaches. CB1 receptor levels in control and PPO KO mice were evaluated by immunoblot analysis. The expression of c-Fos after THC treatment was analysed in several brain areas in wild-type mice and in mice lacking the PPO gene. KEY RESULTS: The hypothermia, supraspinal antinociception and anxiolytic-like effects induced by THC were modulated by orexins through OX2 receptor signalling. OX1 receptors did not seem to be involved in these THC responses. No differences in CB1 receptor levels were found between wild-type and PPO KO mice. THC-induced increase in c-Fos expression was reduced in the central amygdala, medial preoptic area and lateral septum in these mutant mice. CONCLUSIONS AND IMPLICATIONS: Our results provide new findings to further clarify the interaction between orexins and cannabinoids. OX1 and OX2 receptors are differently implicated in the pharmacological effects of cannabinoids. PMID- 26799709 TI - Cultivation of phagotrophic algae with waste activated sludge as a fast approach to reclaim waste organics. AB - Substantial energy is reserved in waste activated sludge (WAS) organics but much of it is difficult to recover because the solid organics require long time to solubilize. In this work we introduced the new approach of recovering WAS organics into the biomass of phagotrophic algae. Phagotrophic algae have the unique ability to grow by ingesting insoluble organic particles including microbial cells. This phagotrophic ability renders the solubilization of WAS organics unnecessary and makes this approach remarkably fast. The approach consists of two stages: a short anaerobic digestion treatment followed by the algal growth on treated WAS. The short anaerobic digestion was exploited to release discrete bacteria from WAS flocs. Phagotrophic algae could then grow rapidly with the released bacteria as well as the solubilized nutrients in the treated WAS. The results showed that WAS organics could be quickly consumed by phagotrophic algae. Among all studied conditions the highest WAS volatile solids (VS) reduction was achieved with 72 h anaerobic digestion and 24 h algal growth. In this optimal process, 28% of WAS VS was reduced, and 41% and 20% of the reduced VS were converted into algal biomass and lipids, respectively. In comparison, only 18% WAS VS were reduced after the same time of aerobic digestion without algae addition. Through this approach, the amount of WAS organics requiring further treatment for final disposal is significantly reduced. With the production of significant amounts of algal biomass and lipids, WAS treatment is expected to be more economical and sustainable in material recycling. PMID- 26799706 TI - SMYD1, an SRF-Interacting Partner, Is Involved in Angiogenesis. AB - Previous studies have demonstrated that Smyd1 plays a critical role in cardiomyocyte differentiation, cardiac morphogenesis and myofibril organization. In this study, we uncovered a novel function of Smyd1 in the regulation of endothelial cells (ECs). Our data showed that Smyd1 is expressed in vascular endothelial cells, and knockdown of SMYD1 in endothelial cells impairs EC migration and tube formation. Furthermore, Co-IP and GST pull-down assays demonstrated that SMYD1 is associated with the Serum Response Factor (SRF). EMSA assays further showed that SMYD1 forms a complex with SRF and enhances SRF DNA binding activity. Our studies indicate that SMYD1 serves as an SRF-interacting protein, enhances SRF DNA binding activity, and is required for EC migration and tube formation to regulate angiogenesis. PMID- 26799710 TI - Enhanced gypsum scaling by organic fouling layer on nanofiltration membrane: Characteristics and mechanisms. AB - To investigate how the characteristics of pregenerated organic fouling layers on nanofiltration (NF) membranes influence the subsequent gypsum scaling behavior, filtration experiments with gypsum were carried out with organic-fouled poly(piperazineamide) NF membranes. Organic fouling layer on membrane was induced by bovine serum albumin (BSA), humic acid (HA), and sodium alginate (SA), respectively. The morphology and components of the scalants, the role of Ca(2+) adsorption on the organic fouling layer during gypsum crystallization, and the interaction forces of gypsum on the membrane surface were investigated. The results indicated that SA- and HA-fouled membranes had higher surface crystallization tendency along with more severe flux decline during gypsum scaling than BSA-fouled and virgin membranes because HA and SA macromolecules acted as nuclei for crystallization. Based on the analyses of Ca(2+) adsorption onto organic adlayers and adhesion forces, it was found that the flux decline rate and extent in the gypsum scaling experiment was positively related to the Ca(2+)-binding capacity of the organic matter. Although the dominant gypsum scaling mechanism was affected by coupling physicochemical effects, the controlling factors varied among foulants. Nevertheless, the carboxyl density of organic matter played an important role in determining surface crystallization on organic-fouled membrane. PMID- 26799711 TI - Modelling the transport of engineered metallic nanoparticles in the river Rhine. AB - As engineered nanoparticles of zinc oxide, titanium dioxide and silver, are increasingly used in consumer products, they will most probably enter the natural environment via wastewater, atmospheric deposition and other routes. The aim of this study is to predict the concentrations of these nanoparticles via wastewater emissions in a typical river system by means of a numerical model. The calculations rely on estimates of the use of nanomaterials in consumer products and the removal efficiency in wastewater treatment plants as well as model calculations of the fate and transport of nanoparticles in a riverine system. The river Rhine was chosen for this work as it is one of the major and best studied rivers in Europe. The study gives insight in the concentrations that can be expected and, by comparing the model results with measurements of the total metal concentrations, of the relative contribution of these emerging contaminants. Six scenarios were examined. Two scenarios concerned the total emission: in the first it was assumed that nanoparticles are only released via wastewater (treated or untreated) and in the second it was assumed that in addition nanoparticles can enter the river system via runoff from the application of sludge as a fertilizer. In both cases the assumption was that the nanoparticles enter the river system as free, unattached particles. Four additional scenarios, based on the total emissions from the second scenario, were examined to highlight the consequences of the assumption of free nanoparticles and the uncertainties about the aggregation processes. If all nanoparticles enter as free particles, roughly a third would end up attached to suspended particulate matter due to the aggregation processes nanoparticles are subject to. For the other scenarios the contribution varies from 20 to 45%. Since the Rhine is a fast flowing river, sedimentation is unlikely to occur, except at the floodplains and the lakes in the downstream regions, as in fact shown by the sediment mass balance. Nanoparticles will therefore be transported along the whole river until they enter the North Sea. For the first scenario, the concentrations predicted for zinc oxide and titanium dioxide nanoparticles are in the order of 0.5 MUg/l, for silver nanoparticles in the order of 5 ng/l. For zinc and titanium compounds this amounts to 5-10% of the measured total metal concentrations, for silver to 2%. For the other scenarios, the predicted nanoparticle concentrations are two to three times higher. While there are still considerable uncertainties in the inputs and consequently the model results, this study predicts that nanoparticles are capable of being transported over long distances, in much the same way as suspended particulate matter. PMID- 26799712 TI - Mathematical modeling of autotrophic denitrification (AD) process with sulphide as electron donor. AB - Autotrophic denitrification (AD) plays a critical role in nitrate removal from organic carbon-deficient wastewaters with a high level of nitrogen oxides. However, the AD process is not included in the current denitrification models, which limits the application of AD technology for wastewater treatment. In this work, a kinetic model for AD process involved 4 processes and 5 components with 9 parameters is established to describe the sulphide biooxidation and nitrite removal process. In this model, 4 oxidation-reduction reactions using sulphide as electronic donor in the AD process are taken into account. The model parameters are optimized by fitting data from the experiments with different combinations of sulphide, sulphur, sulphate, nitrate and nitrite at various concentrations. Model calibration and validation results demonstrate that the developed model is able to reasonably describe the removal rates of nitrate, nitrite, sulphide and sulphur in the AD process. The model simulation results also show that the sulphur term (eta(S)) in the kinetic equations of nitrate, nitrite, sulphur and sulphate remains constant, rather than being controlled by its own concentration. Furthermore, with this model the products of sulphide biooxidation in the AD process, sulphur and sulphate, and their concentrations can be accurately predicted. Therefore, this model provides a strategy to control the sulphate concentration below the discharge limits or recover sulphur as the main end product from sulphide biooxidation. PMID- 26799713 TI - Development of a RAD-Seq Based DNA Polymorphism Identification Software, AgroMarker Finder, and Its Application in Rice Marker-Assisted Breeding. AB - Rapid and accurate genome-wide marker detection is essential to the marker assisted breeding and functional genomics studies. In this work, we developed an integrated software, AgroMarker Finder (AMF: http://erp.novelbio.com/AMF), for providing graphical user interface (GUI) to facilitate the recently developed restriction-site associated DNA (RAD) sequencing data analysis in rice. By application of AMF, a total of 90,743 high-quality markers (82,878 SNPs and 7,865 InDels) were detected between rice varieties JP69 and Jiaoyuan5A. The density of the identified markers is 0.2 per Kb for SNP markers, and 0.02 per Kb for InDel markers. Sequencing validation revealed that the accuracy of genome-wide marker detection by AMF is 93%. In addition, a validated subset of 82 SNPs and 31 InDels were found to be closely linked to 117 important agronomic trait genes, providing a basis for subsequent marker-assisted selection (MAS) and variety identification. Furthermore, we selected 12 markers from 31 validated InDel markers to identify seed authenticity of variety Jiaoyuanyou69, and we also identified 10 markers closely linked to the fragrant gene BADH2 to minimize linkage drag for Wuxiang075 (BADH2 donor)/Jiachang1 recombinants selection. Therefore, this software provides an efficient approach for marker identification from RAD-seq data, and it would be a valuable tool for plant MAS and variety protection. PMID- 26799715 TI - Effects of a change in social activity on quality of life among middle-aged and elderly Koreans: Analysis of the Korean longitudinal study of aging (2006-2012). AB - AIM: The aim of the present study was to examine a relationship between altered social activity and quality of life in later life. METHODS: Data came from the Korean Longitudinal Study of Aging (2006-2012), which consisted of 7096 participants aged 45 years or older. Change in social activity was classified into four categories; that is, "consistent non-participation," "participation to no participation," "no participation to participation" and "consistent participation." Social activity was divided into various elements, and the same analysis was carried out for each element. The linear mixed model was used to investigate the association between changes in social activity and quality of life among middle-aged and elderly Koreans. RESULTS: Those with changes from "participation to no participation" (b 2.253, P < 0.0001), "no participation to participation" (b 3.348, P < 0.0001) and "consistent participation" (b 6.624, P < 0.0001) were more likely to be satisfied with their lives than those with "consistent non-participation" (P < 0.0001 for trend). In addition, the impact of the positive relationship between consistent participation in social activity and quality of life varied across different elements of social activity. The positive association was particularly strong for religious activities, friendship organization, leisure/culture clubs, family/school reunion and voluntary work (b 1.451, P < 0.0004; b 5.049, P < 0.0001; b 4.903, P < 0.0001; b 4.757, P < 0.0001; b 4.562, P < 0.0001; respectively, for consistent participation vs consistent non participation). CONCLUSION: Consistent participation in religious activities, friendship organizations, leisure/culture clubs, family/school reunion ,and volunteer work improves quality of life among middle aged and older Koreans. Geriatr Gerontol Int 2017; 17: 132-141. PMID- 26799714 TI - The bounty of nature for changing the cancer landscape. AB - The landscape of cancer has changed considerably in past several years, due mainly to aggressive screening, accumulation of data from basic and epidemiological studies, and the advances in translational research. Natural anticancer agents have always been a part and parcel of cancer research. The initial focus on natural anticancer agents was in context of their cancer chemopreventive properties but their ability to selectively target oncogenic signaling pathways has also been recognized. In light of the rapid advancements in our understanding of the role of microRNAs, cancer stem cells, and epigenetic events in cancer initiation and progression, a number of natural anticancer agents are showing promise in vitro, in vivo as well as in preclinical studies. Moreover, parent structures of natural agents are being extensively modified with the hope of improving efficacy, specificity, and bioavailability. In this article, we focus on two natural agents, 3,3'-diindolylmethane and garcinol, along with 3,4-difluorobenzo curcumin, a synthetic analog of natural agent curcumin. We showcase how these anticancer agents are changing cancer landscape by modulating novel microRNAs, epigenetic factors, and cancer stem cell markers. These activities are relevant and being appreciated for overcoming drug resistance and inhibition of metastases, the two overarching clinical challenges in modern medicine. PMID- 26799716 TI - Caregiver reasons for tertiary health-care seeking for children aged <=12 years. AB - BACKGROUND: In Turkey, a mandatory referral system is not used. Caregivers, for their children, present directly to health-care providers at all levels. This allows patients to present directly to university hospitals. In this study, reasons for university hospital-treatment seeking by caregivers for child health problems is discussed. METHODS: This was a cross-sectional descriptive study at Dokuz Eylul University Faculty of Medicine, Izmir, Turkey, of 235 caregivers whose children were admitted to the outpatient clinic of the General Pediatrics Department between 4 and 11 April 2013. They completed a questionnaire on demographic data and reasons for presentation to the university hospital. Mann Whitney U-test was used to compare group means, and Pearson chi-squared test for ratios between groups. P <0.05 was considered to be statistically significant. RESULTS: A total of 54.5% of participants lived far from the hospital. The most frequent complaints involved the respiratory tract, among which the most frequent complaint was cough. Time from symptom onset to presentation was >=7 days in 58.3% of patients, and 48.9% had never presented to another institution. The most common reason for choosing the university hospital was the availability of the necessary tests (88.1%). CONCLUSIONS: Despite common use of primary health-care systems, with regard to tertiary hospital presentation, the most important factors for preferring tertiary hospital presentation were caregiver trust in tertiary hospital resources for diagnosis and treatment. PMID- 26799718 TI - Healthcare Quality Indicators for Physiotherapy Management in Hip and Knee Osteoarthritis and Rheumatoid Arthritis: A Delphi Study. AB - OBJECTIVES: The aim of the present study was to develop healthcare quality indicators (HCQIs) for the physiotherapy (PT) management of patients with hip or knee osteoarthritis (HKOA) or rheumatoid arthritis (RA) in the Netherlands. METHODS: Two multidisciplinary expert panels, including patients, were instituted. A draft HCQI set was derived from recommendations included in two existing Dutch PT guidelines for HKOA and RA. The panels suggested additional topics, after which a Delphi procedure was performed. All propositions were scored for their potential to represent good-quality PT care (score range 0-9). Based on predefined rules, the Delphi panel HCQIs were discussed and selected. Lastly, every indicator was rephrased, resulting in its output consisting of a numerator and denominator, to facilitate comparisons within and among practices. RESULTS: After two Delphi rounds, two final sets of 17 HCQI - one for HKOA and one for RA - were composed, both containing 16 process indicators (regarding initial assessment, treatment and evaluation) and one outcome indicator. CONCLUSIONS: Two sets of HCQIs for PT management in HKOA and RA were developed for measuring the quality of PT care in daily clinical practice. Each indicator was formulated in a measurable way. Future research should focus on the feasibility of both indicator sets for daily clinical practice. PMID- 26799719 TI - Transforming Health Care: Body Sensor Networks, Wearables, and the Internet of Things. AB - This paper talks about body sensor networks, wearables, and the Internet of Things. PMID- 26799720 TI - John Rogers and the Ultrathin Limits of Technology: His Flexible, Skin-Mounted Biostamp is Changing the Game for Wearable Diagnostic Devices. AB - In this paper, a flexible, skin-mounted Biostamp changed the game for wearable diagnostic devices. PMID- 26799721 TI - Convergence Revolution Comes to Wearables: Multiple Advances are Taking Biosensor Networks to the Next Level in Health Care. AB - In the field of wearable biomedical sensors, the convergence revolution is more than a fanciful, utopian view of the way innovation should be done. Medical-grade wearable sensors rely on it. Their development requires technical know-how, computing expertise, clinical input, and collaboration-a true meeting of the minds to permit the conversion of wearables from neat gadgets into practical and proficient tools that will propel health care to new heights. Beyond the increasing miniaturization of hardware and the shift to wireless communication technology, flexible electronics and more powerful computing capabilities, including application specific integrated circuits (ASICs) and microelectromechanical systems (MEMS), have enabled new work on body sensor networks (BSNs) that monitor, analyze, and make sense of body signals for the prevention, diagnosis, and treatment of health disorders. Developments in processing, such as sensor-connected nodes combined with evolving algorithms and decreasing power requirements, have also contributed. In addition, new approaches to subjective measures (pain and emotion) have opened possibilities. PMID- 26799722 TI - The End of Seizures and Depression?: New Biosensors That Warn of and Potentially Prevent Health Conditions. AB - The objective tools of engineering should be brought to the challenge of understanding emotions in people, and this could change the way we approach many health conditions, including epilepsy and depression, according to Rosalind Picard, Sc.D., a professor in the Media Laboratory and the director of affective computing research at the Massachusetts Institute of Technology (MIT). She coined the term affective computing and defined it as computing that relates to, arises from or deliberately influences emotions. She is also a founding member of the first IEEE Technical Committee on Wearable Information Technology, which was the precursor to the quantified-self movement that promotes self-monitoring using wearable sensors and other technologies. PMID- 26799723 TI - From Micro to Nano: The Evolution of Wireless Sensor-Based Health Care. AB - Over the past decade, embedded systems and microelectromechanical systems have evolved in a radical way, redefining our standard of living and enhancing the quality of life. Health care, among various other fields, has benefited vastly from this technological development. The concept of using sensors for health care purposes originated in the late 1980s when sensors were developed to measure certain physiological parameters associated with the human body. In traditional sensor nodes, the signal sources are mostly different environmental phenomena (such as temperature, vibration, and luminosity) or man-made events (such as intrusion and mobile target tracking), whereas in case of the physiological sensors, the signal source is living human tissue. These sensor nodes, as their primary sensing element, have a diaphragm that converts pressure into displacement. This displacement, in turn, is subsequently transformed into an electrical signal. The concept of wireless physiological sensor nodes, however, gained popularity in the mid-2000s, with the sensed data from the nodes transmitted to the hub via a wireless medium. The network formed by this heterogeneous set of wireless body sensor nodes is termed a wireless body-area network (WBAN). Each WBAN is essentially a composition of multiple wireless body sensor nodes and a single hub. The hub is primarily responsible for acquisition of the raw sensed data from all the component sensor nodes and first-level aggregation of the data before transmitting the aggregated data for further analysis to a remote data acquisition center. Here, we outline the evolution of WBANs in the context of modern health care and its convergence with nanotechnology. PMID- 26799724 TI - The Body Metric: From Skin Conductance to Brain Waves to Heart Rate, the Measurement of Physiological Function is Playing a Growing Role in Everyday Consumer Technology. AB - From skin conductance to brain waves to heart rate, the measurement of physiological function is playing a growing role in everyday consumer technology. PMID- 26799725 TI - Psychophysiological Monitoring: An Approach for the Diagnosis and Treatment of Mental Health Disorders. AB - The ultimate goal of this work is to improve patient outcomes by increasing the ability to accurately diagnose, efficiently treat, and effectively monitor the response to treatment over time. PMID- 26799726 TI - The Telltale Heartbeat: Heart-Rate Monitors are Taking New Shapes. AB - The pulse rate has long been considered a basic and essential window on a person?s general physical condition. A racing heart could mean a person is at risk for a heart attack or, conversely, simply stressed, excited, or exercising. An erratic heartbeat could be a sign of a thyroid condition or, rather, just an indication that a person has indulged in one too many cups of coffee that morning. A slow pulse, on the other hand, could be a sign of a serious electrical problem within the organ or suggest, to the contrary, that a heart is as strong as an ox. PMID- 26799727 TI - Are Wearables Safe? We Carry Our Smart Devices with Us Everywhere--Even to Bed- But Have We Been Sleeping with the Enemy, or are Cautionary Tales Overinflated? AB - Sometime over the last few years, wearable electronics have become the norm. Whether it's a cell phone attached to a holster at the hip, a smart watch on the wrist, or sensors on and sometimes woven into clothing, these technologies are part of everyday life. Along with this trend, many of the devices are also now collecting and transmitting health information. That is certainly convenient, but the question with any kind of health care device, including wearable medical technology, has always been and continues to be: is it safe? PMID- 26799728 TI - Adalimumab-induced apoptotic enteropathy. PMID- 26799729 TI - Engineering natural heart valves: possibilities and challenges. AB - Heart valve replacement is considered to be the most prevalent treatment approach for cardiac valve-related diseases. Among current solutions for heart valve replacement, e.g. mechanical and bioprosthetic valves, the main shortcoming is the lack of growth capability, repair and remodelling of the substitute valve. During the past three decades, tissue engineering-based approaches have shown tremendous potential to overcome these limitations by the development of a biodegradable scaffold, which provides biomechanical and biochemical properties of the native tissue. Among various scaffolds employed for tissue engineering, the decellularized heart valve (DHV) has attracted much attention, due to its native structure as well as comparable haemodynamic characteristics. Although the human DHV has shown optimal properties for valve replacement, the limitation of valve donors in terms of time and size is their main clinical issue. In this regard, xenogenic DHV can be a promising candidate for heart valve replacement. Xenogenic DHVs have similar composition to human valves, which will overcome the need for human DHVs. The main concern regarding xenogeneic DHV replacement is the immunological reaction and calcification following implantation, weak mechanical properties and insufficient recellularization capacity. In this review, we describe the essential steps required to address these impediments through novel engineering approaches. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26799730 TI - Influence of the use of medicinal plants in medication adherence in elderly people. AB - OBJECTIVE: The objective of this study was to investigate the relationship between the use of medicinal plants and medication adherence in elderly people. METHODS: Observational, cross-sectional study of elderly residents in Cuite-PB, Northeastern Brazil, through a household survey. A stratified proportional and systematic random sample of 240 elders was interviewed in their homes and the use of pharmaceutical medicines and of medicinal plants was assessed by direct examination. The association of medication adherence with socio-demographic, clinical, medication and use of medicinal plants was analysed with multiple logistic regression. RESULTS: The results showed that medication non-adherence increases with use of herbal medicines (adjusted odds ratio 2.022, 95% CI 1.059 3.862, p = 0.03), as well as with the number of different medicinal plants used (adjusted odds ratio 1.937, 95% CI 1.265-2.965, p = 0.002). CONCLUSION/INTERPRETATION: This study provides first-hand evidence that the use of herbal medicines is associated with poor medication adherence. Given the high frequency of the use of herbal medicines, further research into the mechanisms of this association is justified. PMID- 26799732 TI - Remote Sensing Derived Fire Frequency, Soil Moisture and Ecosystem Productivity Explain Regional Movements in Emu over Australia. AB - Species distribution modeling has been widely used in studying habitat relationships and for conservation purposes. However, neglecting ecological knowledge about species, e.g. their seasonal movements, and ignoring the proper environmental factors that can explain key elements for species survival (shelter, food and water) increase model uncertainty. This study exemplifies how these ecological gaps in species distribution modeling can be addressed by modeling the distribution of the emu (Dromaius novaehollandiae) in Australia. Emus cover a large area during the austral winter. However, their habitat shrinks during the summer months. We show evidence of emu summer habitat shrinkage due to higher fire frequency, and low water and food availability in northern regions. Our findings indicate that emus prefer areas with higher vegetation productivity and low fire recurrence, while their distribution is linked to an optimal intermediate (~0.12 m3 m(-3)) soil moisture range. We propose that the application of three geospatial data products derived from satellite remote sensing, namely fire frequency, ecosystem productivity, and soil water content, provides an effective representation of emu general habitat requirements, and substantially improves species distribution modeling and representation of the species' ecological habitat niche across Australia. PMID- 26799733 TI - Intraparenchymal Spinal Cord Ganglioneuroblastoma Originating from the Peripheral Sympathetic Nervous System in a Cat. PMID- 26799734 TI - Perinatal outcomes and intrauterine complications following fetal intervention for congenital heart disease: systematic review and meta-analysis of observational studies. AB - OBJECTIVE: To assess perinatal outcomes and intrauterine complications following fetal intervention for congenital heart disease (CHD). METHODS: A systematic review and meta-analysis were performed following an electronic search of PubMed and Scopus databases (last searched August 2015). Perinatal outcomes that were assessed included fetal death, live birth, preterm delivery < 37 weeks' gestation and neonatal death. Intrauterine complications that were assessed included bradycardia requiring treatment and hemopericardium requiring drainage. Estimated proportions were reported as mean (95% CI). Inconsistency was assessed using the I2 statistic. RESULTS: An electronic search identified 2279 records, of which 29 studies (11 retrospective cohort and 18 case reports) were considered eligible for analysis. Fetal death after treatment of CHD by aortic valvuloplasty was reported in three studies, with a rate of 31% (95% CI, 9-60%), after pulmonary valvuloplasty in one study, with a rate of 25% (95% CI, 10-49%), after septoplasty in one study, with a rate of 14% (95% CI, 6-28%) and after pericardiocentesis and/or pericardioamniotic shunt placement in 24 studies, with a rate of 29% (95% CI, 18-41%). Bradycardia requiring treatment was reported after aortic valvuloplasty in two studies, with a rate of 52% (95% CI, 16-87%), after pulmonary valvuloplasty in one study, with a rate of 44% (95% CI, 23-67%), and after septoplasty in one study, with a rate of 27% (95% CI, 15-43%). CONCLUSIONS: Current evidence on the effectiveness of prenatal intervention for CHD derives mostly from case reports and a few larger series; no study was randomized. Although the results of the meta-analysis are encouraging in terms of perinatal survival, they should be interpreted with caution when comparing with procedures performed after delivery. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26799735 TI - Light-Harvesting Systems Based on Organic Nanocrystals To Mimic Chlorosomes. AB - We report the first highly efficient artificial light-harvesting systems based on nanocrystals of difluoroboron chromophores to mimic the chlorosomes, one of the most efficient light-harvesting systems found in green photosynthetic bacteria. Uniform nanocrystals with controlled donor/acceptor ratios were prepared by simple coassembly of the donors and acceptors in water. The light-harvesting system funneled the excitation energy collected by a thousand donor chromophores to a single acceptor. The well-defined spatial organization of individual chromophores in the nanocrystals enabled an energy transfer efficiency of 95 %, even at a donor/acceptor ratio as high as 1000:1, and a significant fluorescence of the acceptor was observed up to donor/acceptor ratios of 200 000:1. PMID- 26799738 TI - How to overcome hurdles in opiate substitution treatment? A qualitative study with general practitioners in Belgium. AB - BACKGROUND: Opiate substitution treatment (OST) is the administration of opioids (methadone or buprenorphine) under medical supervision for opiate addiction. Several studies indicate a large unmet need for OST in general practice in Antwerp, Belgium. Some hurdles remain before GPs engage in OST prescribing. OBJECTIVES: Formulate recommendations to increase engagement of GPs in OST, applicable to Belgium and beyond. METHODS: In 2009, an exploratory qualitative research was performed using focus group discussions and interviews with GPs. During data collection and analysis, purposive sampling, open and axial coding was applied. The script was composed around the advantages, disadvantages and conditions of engaging in OST in general practice. RESULTS: We conducted six focus groups and two interviews, with GPs experienced in prescribing OST (n = 13), inexperienced GPs (n = 13), and physicians from addiction centres (n = 5). Overall, GPs did not seem very willing to prescribe OST for opiate users. A lack of knowledge about OST and misbehaving patients creates anxiety and makes the GPs reluctant to learn more about OST. The GPs refer to a lack of collaboration with the addiction centres and a need of support (from either addiction centres or experienced GP-colleagues for advice). Important conditions for OST are acceptance of only stable opiate users and more support in emergencies. CONCLUSION: Increasing GPs' knowledge about OST and improving collaboration with addiction centres are essential to increase the uptake of OST in general practice. Special attention could be paid to the role of more experienced colleagues who can act as advising physicians for inexperienced GPs. PMID- 26799740 TI - From C60 to Infinity: Large-Scale Quantum Chemistry Calculations of the Heats of Formation of Higher Fullerenes. AB - We have carried out large-scale computational quantum chemistry calculations on the K computer to obtain heats of formation for C60 and some higher fullerenes with the DSD-PBE-PBE/cc-pVQZ double-hybrid density functional theory method. Our best estimated values are 2520.0 +/- 20.7 (C60), 2683.4 +/- 17.7 (C70), 2862.0 +/ 18.5 (C76), 2878.8 +/- 13.3 (C78), 2946.4 +/- 14.5 (C84), 3067.3 +/- 15.4 (C90), 3156.6 +/- 16.2 (C96), 3967.7 +/- 33.4 (C180), 4364 (C240) and 5415 (C320) kJ mol(-1). In our assessment, we also find that the B3-PW91-D3BJ and BMK-D3(BJ) functionals perform reasonably well. Using the convergence behavior for the calculated per-atom heats of formation, we obtained the formula DeltafH per carbon = 722n(-0.72) + 5.2 kJ mol(-1) (n = the number of carbon atoms), which enables an estimation of DeltafH for higher fullerenes more generally. A slow convergence to the graphene limit is observed, which we attribute to the relatively small proportion of fullerene carbons that are in "low-strain" regions. We further propose that it would take tens, if not hundreds, of thousands of carbons for a fullerene to roughly approach the limit. Such a distinction may be a contributing factor to the discrete properties between the two types of nanomaterials. During the course of our study, we also observe a fairly reliable means for the theoretical calculation of heats of formation for medium-sized fullerenes. This involves the use of isodesmic-type reactions with fullerenes of similar sizes to provide a good balance of the chemistry and to minimize the use of accompanying species. PMID- 26799741 TI - Nanochemistry and Nanomedicine for Nanoparticle-based Diagnostics and Therapy. PMID- 26799742 TI - Correction: Still Heart Encodes a Structural HMT, SMYD1b, with Chaperone-Like Function during Fast Muscle Sarcomere Assembly. PMID- 26799743 TI - Improved Muscle Function in Duchenne Muscular Dystrophy through L-Arginine and Metformin: An Investigator-Initiated, Open-Label, Single-Center, Proof-Of-Concept Study. AB - Altered neuronal nitric oxide synthase function in Duchenne muscular dystrophy leads to impaired mitochondrial function which is thought to be one cause of muscle damage in this disease. The study tested if increased intramuscular nitric oxide concentration can improve mitochondrial energy metabolism in Duchenne muscular dystrophy using a novel therapeutic approach through the combination of L-arginine with metformin. Five ambulatory, genetically confirmed Duchenne muscular dystrophy patients aged between 7-10 years were treated with L-arginine (3 x 2.5 g/d) and metformin (2 x 250 mg/d) for 16 weeks. Treatment effects were assessed using mitochondrial protein expression analysis in muscular biopsies, indirect calorimetry, Dual-Energy X-Ray Absorptiometry, quantitative thigh muscle MRI, and clinical scores of muscle performance. There were no serious side effects and no patient dropped out. Muscle biopsy results showed pre-treatment a significantly reduced mitochondrial protein expression and increased oxidative stress in Duchenne muscular dystrophy patients compared to controls. Post treatment a significant elevation of proteins of the mitochondrial electron transport chain was observed as well as a reduction in oxidative stress. Treatment also decreased resting energy expenditure rates and energy substrate use shifted from carbohydrates to fatty acids. These changes were associated with improved clinical scores. In conclusion pharmacological stimulation of the nitric oxide pathway leads to improved mitochondria function and clinically a slowing of disease progression in Duchenne muscular dystrophy. This study shall lead to further development of this novel therapeutic approach into a real alternative for Duchenne muscular dystrophy patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02516085. PMID- 26799744 TI - Clinical Characteristics and Prognostic Significance of TERT Promoter Mutations in Cancer: A Cohort Study and a Meta-Analysis. AB - BACKGROUND: The prevalence of telomerase reverse transcriptase (TERT) promoter mutations (pTERTm) in non-small-cell lung cancer (NSCLC) have been investigated, but the results were inconsistent. In addition, several studies have analysed the role of pTERTm in the etiology of various types of cancers, however, the results also remain inconsistent. METHODS: The genomic DNA sequence of 103 NSCLC samples were analysed to investigate the frequency of pTERTm in these patients and to establish whether these mutations are associated with their clinical data. Furthermore, a meta-analysis based on previously published articles and our cohort study was performed to investigate the association of pTERTm with patient gender, age at diagnosis, metastasis status, tumour stage and cancer prognosis (5 year overall survival rate). RESULTS: In the cohort study, 4 patients had C228T and 2 had C250T, with a total mutation frequency up to 5.8%. Significant difference of clinical data between pTERTm carriers and noncarriers was only found in age at diagnosis. In the meta-analysis, We found that pTERTm carriers in cancer patients are older than noncarriers (Mean difference (MD) = 5.24; 95% confidence interval [CI], 2.00 to 8.48), male patients were more likely to harbour pTERTm (odds Ratios (OR) = 1.38; 95% CI, 1.22 to 1.58), and that pTERTm had a significant association with distant metastasis (OR = 3.78; 95% CI, 2.45 to 5.82), a higher tumour grade in patients with glioma (WHO grade III, IV vs. I, II: OR, 2.41; 95% CI, 1.88 to 3.08) and a higher tumour stage in other types of cancer (III, IV vs. I, II: OR, 2.48; 95% CI, 1.48 to 4.15). pTERTm was also significantly associated with a greater risk of death (hazard ratio = 1.71; 95% CI, 1.41 to 2.08). CONCLUSIONS: pTERTm are a moderately prevalent genetic event in NSCLC. The current meta-analysis indicates that pTERTm is associated with patient age, gender and distant metastasis. It may serves as an adverse prognostic factor in individuals with cancers. PMID- 26799746 TI - Vascular Endothelium-Dependent and Independent Actions of Oleanolic Acid and Its Synthetic Oleanane Derivatives as Possible Mechanisms for Hypotensive Effects. AB - PURPOSE: Plant-derived oleanolic acid (OA) and its related synthetic derivatives (Br-OA and Me-OA) possess antihypertensive effects in experimental animals. The present study investigated possible underlying mechanisms in rat isolated single ventricular myocytes and in vascular smooth muscles superfused at 37 degrees C. METHODS: Cell shortening was assessed at 1 Hz using a video-based edge-detection system and the L-type Ca2+ current (ICaL) was measured using the whole-cell patch clamp technique in single ventricular myocytes. Isometric tension was measured using force transducer in isolated aortic rings and in mesenteric arteries. Vascular effects were measured in endothelium-intact and denuded vessels in the presence of various enzyme or channel inhibitors. RESULTS: OA and its derivatives increased cell shortening in cardiomyocytes isolated from normotensive rats but had no effect in those isolated from hypertensive animals. These triterpenes also caused relaxation in aortic rings and in mesenteric arteries pre-contracted with either phenylephrine or KCl-enriched solution. The relaxation was only partially inhibited by endothelium denudation, and also partly inhibited by the cyclooxygenase (COX) inhibitor indomethacin, with no additional inhibitory effect of the NO synthase inhibitor, N-omega-Nitro-L-arginine. A combination of both ATP dependent channel inhibition by glibenclaminde and voltage-dependent K+ channel inhibition by 4-aminopyridine was necessary to fully inhibit the relaxation. CONCLUSION: These data indicate that the effects of OA and its derivatives are mediated via both endothelium-dependent and independent mechanisms suggesting the involvement of COX in the endothelium-dependent effects and of vascular muscle K+ channels in the endothelium-independent effects. Finally, our results support the view that the antihypertensive action of OA and its derivatives is due to a decrease of vascular resistance with no negative inotropic effect on the heart. PMID- 26799747 TI - Evaluation of antinociceptive and antidiarrhoeal properties of Manilkara zapota leaves in Swiss albino mice. AB - Context Manilkara zapota (L.). P. Royen. (Sapotaceae) has been used in folk medicine to treat pain, diarrhoea, inflammation, arthralgia, and other disorders. Objective Screening of Manilkara zapota leaves ethanol extract and its different solvent soluble fractions for possible antinociceptive and antidiarrhoeal activities in Swiss albino mice. Materials and methods The extract and various fractions (200 and 400 mg/kg body weight; p.o.) were tested for peripheral and central antinociceptive activity by acetic acid-induced writhing and radiant heat tail-flick method, respectively; castor oil-induced diarrhoeal model was used to evaluate antidiarrhoeal activity at both doses. All the samples were administered once in a day and the duration of study was approximately 5 h. Results Ethanol extract (400 mg/kg), petroleum ether fraction (400 mg/kg), and ethyl acetate fraction (400 mg/kg) showed significant peripheral antinociceptive activity having 59.89, 58.24, and 46.7% (p < 0.001) of writhing inhibition, respectively, which is comparable with that of standard diclofenac (59.34% inhibition). The ethanol extract (400 mg/kg) and petroleum ether fraction (400 mg/kg) also showed promising central analgesic activity having 74.15 and 82.15% (p < 0.001) elongation of reaction time, respectively, at 90 min after administration of sample which is also similar to that obtained by morphine (85.84% elongation). In antidiarrhoeal activity screening, ethanol extract (200 and 400 mg/kg) showed significant inhibition of defecation by 53.57 and 60.71%, respectively (p < 0.001) compared with that of loperamide (71.42%). Discussion and conclusion The findings of the studies demonstrated antinociceptive and antidiarrhoeal activities of M. zapota leaves which could be the therapeutic option against pain and diarrhoeal disease. PMID- 26799745 TI - Adjustment of Cell-Type Composition Minimizes Systematic Bias in Blood DNA Methylation Profiles Derived by DNA Collection Protocols. AB - Differences in DNA collection protocols may be a potential confounder in epigenome-wide association studies (EWAS) using a large number of blood specimens from multiple biobanks and/or cohorts. Here we show that pre-analytical procedures involved in DNA collection can induce systematic bias in the DNA methylation profiles of blood cells that can be adjusted by cell-type composition variables. In Experiment 1, whole blood from 16 volunteers was collected to examine the effect of a 24 h storage period at 4 degrees C on DNA methylation profiles as measured using the Infinium HumanMethylation450 BeadChip array. Our statistical analysis showed that the P-value distribution of more than 450,000 CpG sites was similar to the theoretical distribution (in quantile-quantile plot, lambda = 1.03) when comparing two control replicates, which was remarkably deviated from the theoretical distribution (lambda = 1.50) when comparing control and storage conditions. We then considered cell-type composition as a possible cause of the observed bias in DNA methylation profiles and found that the bias associated with the cold storage condition was largely decreased (lambda adjusted = 1.14) by taking into account a cell-type composition variable. As such, we compared four respective sample collection protocols used in large-scale Japanese biobanks or cohorts as well as two control replicates. Systematic biases in DNA methylation profiles were observed between control and three of four protocols without adjustment of cell-type composition (lambda = 1.12-1.45) and no remarkable biases were seen after adjusting for cell-type composition in all four protocols (lambda adjusted = 1.00-1.17). These results revealed important implications for comparing DNA methylation profiles between blood specimens from different sources and may lead to discovery of disease-associated DNA methylation markers and the development of DNA methylation profile-based predictive risk models. PMID- 26799749 TI - New challenges and promises in solid organ transplantation pharmacogenetics: the genetic variability of proteins involved in the pharmacodynamics of immunosuppressive drugs. AB - Interindividual variability in immunosuppressive drug responses might be partly explained by genetic variants in proteins involved in the immune response or associated with IS pharmacodynamics. On a general basis, the pharmacogenetics of drug target proteins is less known and understood than that of proteins involved in drug disposition pathways. The aim of this review is to facilitate research related to the pharmacodynamics of the main immunosuppressive drugs used in solid organ transplantation. We elaborated a quality of evidence grading system based on a literature review and identified 'highly recommended', 'recommended' or 'potential' candidates for further research. It is likely that a number of additional rare variants might further explain drug response phenotypes in transplantation, and particularly the most severe ones. The advent of next generation sequencing will help to identify those variants. PMID- 26799750 TI - Translational modeling and simulation approaches for molecularly targeted small molecule anticancer agents from bench to bedside. AB - INTRODUCTION: Recent advances in molecular biology have enabled personalized cancer therapies with molecularly targeted agents (MTAs), which offer a promising future for cancer therapy. Dynamic modeling and simulation (M&S) is a powerful mathematical approach linking drug exposures to pharmacological responses, providing a quantitative assessment of in vivo drug potency. Accordingly, a growing emphasis is being placed upon M&S to quantitatively understand therapeutic exposure-response relationships of MTAs in nonclinical models. AREAS COVERED: An overview of M&S approaches for MTAs in nonclinical models is presented with discussion about mechanistic extrapolation of antitumor efficacy from bench to bedside. Emphasis is placed upon recent advances in M&S approaches linking drug exposures, biomarker responses (e.g. target modulation) and pharmacological outcomes (e.g. antitumor efficacy). EXPERT OPINION: For successful personalized cancer therapies with MTAs, it is critical to mechanistically and quantitatively understand their exposure-response relationships in nonclinical models, and to logically and properly apply such knowledge to the clinic. Particularly, M&S approaches to predict pharmacologically active concentrations of MTAs in patients based upon nonclinical data would be highly valuable in guiding the design and execution of clinical trials. Proactive approaches to understand their exposure-response relationships could substantially increase probability of achieving a positive proof-of-concept in the clinic. PMID- 26799751 TI - Outcomes of Re-Intervention for Laparoscopic Transperitoneal Pyeloplasty in Children. AB - BACKGROUND: There is no consensus for the management of failed laparoscopic pyeloplasty in pediatric surgical patients, and only limited publications are available. We evaluated here the clinical outcomes of re-intervention for failed laparoscopic transperitoneal pyeloplasty in infants and children. MATERIALS AND METHODS: Retrospective review of all children who had undergone laparoscopic transperitoneal dismembered Anderson-Hynes pyeloplasty for ureteropelvic junction obstruction from 2002 to 2013 was performed. Patients' demographics, indications, operative details, and outcomes for primary operation as well as re-intervention were studied. RESULTS: There were 42 patients with a median age of 20 months (range, 3-192 months) and a median body weight of 12 kg (range, 6-56 kg) who underwent a total of 46 laparoscopic transperitoneal pyeloplasties during the study period. The median operative time and blood loss were 193 minutes (range, 115-480 minutes) and trace amount (range, trace amount to 400 mL), respectively. No conversion was reported. Ten cases (22%) required re-intervention. No statistically significant risk factor for failed pyeloplasty was identified. Indications for re-intervention included deterioration of differential renal function (n = 6), progressive hydronephrosis (n = 1), urinary ascites (n = 2), and urosepsis (n = 1). Median time of re-intervention was 6.5 +/- 38 months postpyeloplasty. Re-intervention was categorized into the redo pyeloplasty group (n = 6) and the urinary diversion group (n = 4) (insertion of double-J ureteral stent or endopyelotomy) with success rates of 50% and 25%, respectively. Among the redo pyeloplasty group, 3 patients underwent redo laparoscopic pyeloplasty, and all of them had drainage restored with a median improvement in differential renal function of 11%. The mean follow-up duration was 77 +/- 38 months. CONCLUSIONS: Laparoscopic transperitoneal pyeloplasty is safe and feasible in children. Redo pyeloplasty is a more favorable re-intervention compared with urinary diversion in our series. Redo laparoscopic pyeloplasty has been shown to improve differential renal function. PMID- 26799752 TI - Correlation among physical and electrochemical behaviour of nanostructured electrolytic manganese dioxide from leach liquor and synthetic for aqueous asymmetric capacitor. AB - An attempt has been made to correlate the differences in structural parameters, surface areas, morphology etc. with the electrochemical capacitive behaviour of the EMDs. The nanostructured electrolytic manganese dioxides (EMD) have been synthesized through electrodepositing MnO2 from two different leach liquors and a synthetic analogue thereof. The structural and chemical state was determined using X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) respectively. Multiplet structure determination led to estimates of the manganese valence states present in the EMD. The EMDs have been tested in an asymmetric capacitor which we have developed. This used activated carbon as the negative electrode and the various EMDs as the positive electrode. Aqueous 2 M NaOH solution was used as the electrolyte. The capacitor achieved 1.6 V corresponding to a capacitance of ~50 F g(-1) of the EMDs from leach liquors. The EMD derived from the synthetic solution showed an inferior capacitance of 25 F g(-1). Extended cycling (2000 cycles), showed 100% capacity retention was achieved for one EMD produced from the leach liquor derived from low-grade manganese ore/residue. This outstanding capacitor performance was correlated with the presence of a nanofibrous morphology. These findings open up the possibility of extracting a high performance EMD product from a low cost, low-grade source of manganese. PMID- 26799755 TI - Endoscopic management of choledocholithiasis and cholelithiasis in patients with cirrhosis. AB - Treatment of choledocholithiasis and cholelithiasis in patients with cirrhosis often requires diagnostic and therapeutic endoscopy such as endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). Patients with underlying cirrhosis may have coagulopathy, hepatic encephalopathy, ascites and other comorbidities associated with cirrhosis that can make endoscopic therapy challenging and can be associated with a higher risk of adverse events. Given the unique derangements of physiologic parameters associated with cirrhosis this population requires a truly multifaceted and multidisciplinary understanding between therapeutic endoscopists, hepatologists and anesthesiologists. For therapeutic endoscopists, it is critical to be aware of the specific issues unique to this population of patients to optimize outcomes and avoid adverse events. The epidemiology of gallstone disease, the diagnostic and therapeutic approach to patients with varying degree of hepatic dysfunction, and a review of the available literature in this area are presented. PMID- 26799756 TI - The Word Outside and the Pictures in Our Heads: Contingent Framing Effects of Labels on Health Policy Preferences by Political Ideology. AB - This study uses data from systematic Web image search results and two randomized survey experiments to analyze how frames commonly used in public debates about health issues, operationalized here as alternative word choices, influence public support for health policy reforms. In Study 1, analyses of Bing (N = 1,719), Google (N = 1,872), and Yahoo Images (N = 1,657) search results suggest that the images returned from the search query "sugar-sweetened beverage" are more likely to evoke health-related concepts than images returned from a search query about "soda." In contrast, "soda" search queries were more likely to incorporate brand related concepts than "sugar-sweetened beverage" search queries. In Study 2, participants (N = 206) in a controlled Web experiment rated their support for policies to reduce consumption of these drinks. As expected, strong liberals had more support for policies designed to reduce the consumption of these drinks when the policies referenced "soda" compared to "sugar-sweetened beverage." To the contrary, items describing these drinks as "soda" produced lower policy support than items describing them as "sugar-sweetened beverage" among strong conservatives. In Study 3, participants (N = 1,000) in a national telephone survey experiment rated their support for a similar set of policies. Results conceptually replicated the previous Web-based experiment, such that strong liberals reported greater support for a penny-per-ounce taxation when labeled "soda" versus "sugar-sweetened beverages." In both Studies 2 and 3, more respondents referred to brand-related concepts in response to questions about "sugar-sweetened beverages" compared to "soda." We conclude with a discussion of theoretical and methodological implications for studying framing effects of labels. PMID- 26799758 TI - Breast cancer in BRCA mutation carriers: medical treatment. AB - About 10% of breast cancers are associated with the inheritance of autosomal dominant breast cancer susceptibility alleles BRCA1 and BRCA2. Until recently, the medical management of BRCA mutation-associated breast cancer has not differed from that of the sporadic breast cancer counterpart. However, there is mounting evidence that this molecular alteration confers sensitivity or resistance to systemic therapies that can be exploited in terms of medical management. For example, studies support the use of platinum salts chemotherapy in BRCA mutated cancers. Moreover, a number of targeted therapies are showing activity in BRCA mutation carriers. Above all, BRCA defective tumor cells are particularly sensitive to Poly(ADP-ribose) polymerase (PARP) inhibitors. This review will summarize the state of the art of the medical treatment of breast cancer in BRCA mutation carriers, with a particular focus on chemotherapies and targeted therapies. PMID- 26799759 TI - Laparoscopic power morcellation of presumed fibroids. AB - Uterine leiomyoma is a highly prevalent benign gynecologic neoplasm that affects women of reproductive age. Surgical procedures commonly employed to treat symptomatic uterine fibroids include myomectomy or total or sub-total hysterectomy. These procedures, when performed using minimally invasive techniques, reduce the risks of intraoperative and postoperative morbidity and mortality; however, in order to remove bulky lesions from the abdominal cavity through laparoscopic ports, a laparoscopic power morcellator must be used, a device with rapidly spinning blades to cut the uterine tissue into fragments so that it can be removed through a small incision. Although the minimal invasive approach in gynecological surgery has been firmly established now in terms of recovery and quality of life, morcellation is associated with rare but sometimes serious adverse events. Parts of the morcellated specimen may be spread into the abdominal cavity and enable implantation of cells on the peritoneum. In case of unexpected sarcoma the dissemination may upstage disease and affect survival. Myoma cells may give rise to 'parasitic' fibroids, but also implantation of adenomyotic cells and endometriosis has been reported. Finally the morcellation device may cause inadvertent injury to internal structures, such as bowel and vessels, with its rotating circular knife. In this article it is described how to estimate the risk of sarcoma in a presumed fibroid based on epidemiologic, imaging and laboratory data. Furthermore the first literature results of the in bag morcellation are reviewed. With this procedure the specimen is contained in an insufflated sterile bag while being morcellated, potentially preventing spillage of tissue but also making direct morcellation injuries unlikely to happen. PMID- 26799760 TI - Ordered Silica Nanoparticles Grown on a Three-Dimensional Carbon Fiber Architecture Substrate with Siliconborocarbonitride Ceramic as a Thermal Barrier Coating. AB - Hierarchical structure consisting of ordered silica nanoparticles grown onto carbon fiber (CF) has been fabricated to improve the interfacial properties between the CFs and polymer matrix. To improve the reactivity of CFs, their surface was modified using poly(1,4-phenylene diisocyanate) (PPDI) via in situ polymerization, which also resulted in the distribution of numerous isocyanate groups on the surface of CFs. Silica nanoparticles were modified on the interface of CF-PPDI by chemical grafting method. The microstructure, chemical composition, and interfacial properties of CFs with ordered silica nanoparticles were comprehensively investigated by scanning electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. Results indicated an obvious increase in the interfacial shear strength, compared to that of CF precursor, which was attributed to silica nanoparticles interacting with the epoxy resin. Furthermore, siliconborocarbonitride (SiBCN) ceramic was used as thermal barrier coating to enhance 3D CF architecture substrate antioxidant and ablation properties. Thermogravimetric results show that the thermal stability of the CF with SiBCN ceramic layer has a marked increase at high temperature. PMID- 26799761 TI - Electromembrane extraction of gonadotropin-releasing hormone agonists from plasma and wastewater samples. AB - In the present study, for the first time electromembrane extraction followed by high performance liquid chromatography coupled with ultraviolet detection was optimized and validated for quantification of four gonadotropin-releasing hormone agonist anticancer peptides (alarelin, leuprolide, buserelin and triptorelin) in biological and aqueous samples. The parameters influencing electromigration were investigated and optimized. The membrane consists 95% of 1-octanol and 5% di-(2 ethylhexyl)-phosphate immobilized in the pores of a hollow fiber. A 20 V electrical field was applied to make the analytes migrate from sample solution with pH 7.0, through the supported liquid membrane into an acidic acceptor solution with pH 1.0 which was located inside the lumen of hollow fiber. Extraction recoveries in the range of 49 and 71% within 15 min extraction time were obtained in different biological matrices which resulted in preconcentration factors in the range of 82-118 and satisfactory repeatability (7.1 < RSD% < 19.8). The method offers good linearity (2.0-1000 ng/mL) with estimation of regression coefficient higher than 0.998. The procedure allows very low detection and quantitation limits of 0.2 and 0.6 ng/mL, respectively. Finally, it was applied to determination and quantification of peptides in human plasma and wastewater samples and satisfactory results were yielded. PMID- 26799762 TI - Pol II CTD Code Light. AB - In this issue of Molecular Cell, Schuller et al. (2016) and Suh et al. (2016) describe genetic and mass spectrometry methodologies for mapping phosphorylation sites on the tandem repeats of the RNA polymerase II CTD. The results suggest that the CTD Code may be simpler than expected. PMID- 26799763 TI - Chasing One-Carbon Units to Understand the Role of Serine in Epigenetics. AB - In this issue of Molecular Cell, Maddocks et al. (2016) use stable isotope tracing, mass spectrometry, and nutrient modulation in cancer cells to highlight the role of serine in supporting methylation through maintenance of nucleotide levels. PMID- 26799764 TI - Direct Analysis of Phosphorylation Sites on the Rpb1 C-Terminal Domain of RNA Polymerase II. AB - Dynamic interactions between RNA polymerase II and various mRNA-processing and chromatin-modifying enzymes are mediated by the changing phosphorylation pattern on the C-terminal domain (CTD) of polymerase subunit Rpb1 during different stages of transcription. Phosphorylations within the repetitive heptamer sequence (YSPTSPS) of CTD have primarily been defined using antibodies, but these do not distinguish different repeats or allow comparative quantitation. Using a CTD modified for mass spectrometry (msCTD), we show that Ser5-P and Ser2-P occur throughout the length of CTD and are far more abundant than other phosphorylation sites. msCTD extracted from cells mutated in several CTD kinases or phosphatases showed the expected changes in phosphorylation. Furthermore, msCTD associated with capping enzyme was enriched for Ser5-P while that bound to the transcription termination factor Rtt103 had higher levels of Ser2-P. These results suggest a relatively sparse and simple "CTD code." PMID- 26799765 TI - Heptad-Specific Phosphorylation of RNA Polymerase II CTD. AB - The carboxy-terminal domain (CTD) of RNA polymerase II (Pol II) consists of heptad repeats with the consensus motif Y1-S2-P3-T4-S5-P6-S7. Dynamic phosphorylation of the CTD coordinates Pol II progression through the transcription cycle. Here, we use genetic and mass spectrometric approaches to directly detect and map phosphosites along the entire CTD. We confirm phosphorylation of CTD residues Y1, S2, T4, S5, and S7 in mammalian and yeast cells. Although specific phosphorylation signatures dominate, adjacent CTD repeats can be differently phosphorylated, leading to a high variation of coexisting phosphosites in mono- and di-heptad CTD repeats. Inhibition of CDK9 kinase specifically reduces S2 phosphorylation levels within the CTD. PMID- 26799766 TI - Regulation of vitellogenin (vtg1) and estrogen receptor (er) gene expression in zebrafish (Danio rerio) following the administration of Cd2+ and 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). AB - We evaluated the individual and joint estrogenic effects of cadmium (Cd(2+)) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the zebrafish liver (ZFL) cell line, zebrafish embryo, larvae and the liver of adult zebrafish. The mRNA expression of vtg1 was inhibited by Cd(2+), but unaffected by TCDD in ZFL cells. Similar changes in the mRNA levels of ERalpha, ERbeta1, ERbeta2 and GPER (G protein coupled estrogen receptor) in ZFL cells were also observed. Deletion mutants of vtg1 gene promoters were constructed to investigate transcriptional regulation, and we found that all of the constructs failed to respond to TCDD or Cd(2+). However, after co-transfection with a vtg1 promoter-luciferase construct to the ERalpha, ERbeta1, ERbeta2 and GPER expression vectors, decreased luciferase activity was observed in the ERalpha co-transfection group after treatment with Cd(2+), suggesting that ERalpha participates in vtg1 transcriptional regulation and is affected by Cd(2+). Differences in the regulation of the mRNA levels of these genes were also observed between different developmental stages and between the livers of male and female zebrafish. PMID- 26799768 TI - Rhenium Dichalcogenides: Layered Semiconductors with Two Vertical Orientations. AB - The rhenium and technetium diselenides and disulfides are van der Waals layered semiconductors in some respects similar to more well-known transition metal dichalcogenides (TMD) such as molybdenum sulfide. However, their symmetry is lower, consisting only of an inversion center, so that turning a layer upside down (that is, applying a C2 rotation about an in-plane axis) is not a symmetry operation, but reverses the sign of the angle between the two nonequivalent in plane crystallographic axes. A given layer thus can be placed on a substrate in two symmetrically nonequivalent (but energetically similar) ways. This has consequences for the exploitation of the anisotropic properties of these materials in TMD heterostructures and is expected to lead to a new source of domain structure in large-area layer growth. We produced few-layer ReS2 and ReSe2 samples with controlled "up" or "down" orientations by micromechanical cleavage and we show how polarized Raman microscopy can be used to distinguish these two orientations, thus establishing Raman as an essential tool for the characterization of large-area layers. PMID- 26799769 TI - The herbicide atrazine induces hyperactivity and compromises tadpole detection of predator chemical cues. AB - The ability to detect chemical cues is often critical for freshwater organisms to avoid predation and find food and mates. In particular, reduced activity and avoidance of chemical cues signaling predation risk are generally adaptive behaviors that reduce prey encounter rates with predators. The present study examined the effects of the common herbicide atrazine on the ability of Cuban tree frog (Osteopilus septentrionalis) tadpoles to detect and respond to chemical cues from larval dragonfly (Libellulidae sp.) predators. Tadpoles exposed to an estimated environmental concentration of atrazine (calculated using US Environmental Protection Agency software; measured concentration, 178 MUg/L) were significantly hyperactive relative to those exposed to solvent control. In addition, control tadpoles significantly avoided predator chemical cues, but tadpoles exposed to atrazine did not. These results are consistent with previous studies that have demonstrated that ecologically relevant concentrations of atrazine can induce hyperactivity and impair the olfactory abilities of other freshwater vertebrates. The authors call for additional studies examining the role of chemical contaminants in disrupting chemical communication and the quantification of subsequent impacts on the fitness and population dynamics of wildlife. Environ Toxicol Chem 2016;35:2239-2244. (c) 2016 SETAC. PMID- 26799770 TI - A novel LabVIEW-based multi-channel non-invasive abdominal maternal-fetal electrocardiogram signal generator. AB - This paper describes the design, construction, and testing of a multi-channel fetal electrocardiogram (fECG) signal generator based on LabVIEW. Special attention is paid to the fetal heart development in relation to the fetus' anatomy, physiology, and pathology. The non-invasive signal generator enables many parameters to be set, including fetal heart rate (FHR), maternal heart rate (MHR), gestational age (GA), fECG interferences (biological and technical artifacts), as well as other fECG signal characteristics. Furthermore, based on the change in the FHR and in the T wave-to-QRS complex ratio (T/QRS), the generator enables manifestations of hypoxic states (hypoxemia, hypoxia, and asphyxia) to be monitored while complying with clinical recommendations for classifications in cardiotocography (CTG) and fECG ST segment analysis (STAN). The generator can also produce synthetic signals with defined properties for 6 input leads (4 abdominal and 2 thoracic). Such signals are well suited to the testing of new and existing methods of fECG processing and are effective in suppressing maternal ECG while non-invasively monitoring abdominal fECG. They may also contribute to the development of a new diagnostic method, which may be referred to as non-invasive trans-abdominal CTG + STAN. The functional prototype is based on virtual instrumentation using the LabVIEW developmental environment and its associated data acquisition measurement cards (DAQmx). The generator also makes it possible to create synthetic signals and measure actual fetal and maternal ECGs by means of bioelectrodes. PMID- 26799771 TI - Association of postpartum depressive symptoms and urinary incontinence. A cohort study. AB - OBJECTIVE: Our objective was to clarify whether de novo urinary incontinence (UI) in the postpartum period is associated with depressive symptoms or antidepressant drug consumption. STUDY DESIGN: 2002 pregnant women were recruited between 2003 and 2006 for the EDEN mother-child cohort. This analysis included 1413 women who reported no UI before pregnancy. Severity of UI was assessed by the Sandvik index. At 4 and 12 months postpartum, depressive symptoms were assessed by the Edinburgh Postpartum Depression Scale (EPDS>=10 defines depressive symptoms) and consumption of antidepressant drugs was reported. RESULTS: At 4 months postpartum, 198 women (14%) reported de novo UI; 74% (n=146) reported mild UI, 26% (n=52) moderate, and none severe; prevalence of depressive symptoms was higher in women with than without UI (22.1% vs. 15.9%, p=0.045), and consumption of antidepressant drugs was more frequent (4.7% vs. 1.4%, p=0.005). At 12 months postpartum, the mean (+/-SD) EPDS score differed between women with than without UI (7.30+/-3.46 vs. 6.57+/-3.72, p=0.016) but was half that at 4 months postpartum. The incidence of new cases of depressive symptoms or antidepressant consumption at 12 months was greater with than without UI (23.8% vs. 15.3%, p=0.012). CONCLUSIONS: Although UI is mild in most cases at 4 months postpartum, it is followed by more new cases of depressive symptoms or antidepressant consumption at 12 months. PMID- 26799772 TI - Application of SonoVue combined with three-dimensional color power angiography in the diagnosis and prognosis evaluation of intrauterine adhesion. AB - OBJECTIVE: To investigate the significance of the related indexes of three dimensional color power angiography (3D-CPA) combined with SonoVue angiography in the diagnosis and prognosis evaluation of intrauterine adhesion (IUA). METHODS: The accuracy, sensitivity, and specificity were evaluated between 3D-TVS and hysteroscopy. Endometrial thickness, volume (V), mean gray value (MG), vascularization index (VI), flow index (FI), vascularization flow index (VFI), and other related indexes before and after the angiography were compared. According to the hysteroscopy findings, the patients were divided into three groups: mild, medium, and severe. The endometrial thickness at 3 months postoperatively and the pregnancy rates at 1 year postoperatively were compared. RESULTS: Compared with the hysteroscopy, sensitivity: 0.970 (0.021), specificity: 0.667 (0.086), (the values inside the bracket were the standard error), positive likelihood ratio: 2.909, negative likelihood ratio: 0.045. There was a significant difference in endometrial thickness and V between the three groups (P<0.05), and there was a significant difference in MG, VI, FI, and VFI between the mild and severe group (P>0.05). During intravenous injection of SonoVue, the blood flow of each group increased (P<0.001), and the VI, FI, and VFI of each group were significantly different (P<0.05). Compared with the preoperative values, the endometrial thickness, V, MG, VI, FI, and VFI significantly changed at 3 months postoperatively (P<0.05). The mild group and high VI group had a higher pregnancy success rate at one year postoperatively. CONCLUSION: 3D-CPA can indirectly diagnose IUA, and may play an important role in prognosis assessment. PMID- 26799774 TI - Spatiotemporal Characteristics of QRS Complexes Enable the Diagnosis of Brugada Syndrome Regardless of the Appearance of a Type 1 ECG. AB - INTRODUCTION: The diagnosis of Brugada syndrome based on the ECG is hampered by the dynamic nature of its ECG manifestations. Brugada syndrome patients are only 25% likely to present a type 1 ECG. The objective of this study is to provide an ECG diagnostic criterion for Brugada syndrome patients that can be applied consistently even in the absence of a type 1 ECG. METHODS AND RESULTS: We recorded 67-lead body surface potential maps from 94 Brugada syndrome patients and 82 controls (including right bundle branch block patients and healthy individuals). The spatial propagation direction during the last r' wave and the slope at the end of the QRS complex were measured and compared between patients groups. Receiver-operating characteristic curves were constructed for half of the database to identify optimal cutoff values; sensitivity and specificity for these cutoff values were measured in the other half of the database. A spontaneous type 1 ECG was present in only 30% of BrS patients. An orientation in the sagittal plane < 101o during the last r' wave and a descending slope < 9.65 mV/s enables the diagnosis of the syndrome with a sensitivity of 69% and a specificity of 97% in non-type 1 Brugada syndrome patients. CONCLUSION: Spatiotemporal characteristics of surface ECG recordings can enable a robust identification of BrS even without the presence of a type 1 ECG. PMID- 26799775 TI - Estimation of Potentials of Mean Force from Nonequilibrium Pulling Simulations Using Both Minh-Adib Estimator and Weighted Histogram Analysis Method. AB - Nonequilibrium pulling simulations have been a useful approach for investigating a variety of physical and biological problems. The major target in the simulations is to reconstruct reliable potentials of mean force (PMFs) or unperturbed free-energy profiles for quantitatively addressing both equilibrium mechanistic properties and contributions from nonequilibrium processes. While several current nonequilibrium methods were shown to be accurate in computing free-energy profiles in systems with relatively simple dynamics, they have proved to be unsuitable in more complicated systems. To extend the applicability of nonequilibrium sampling, we demonstrate a novel method that combines Minh-Adib's bidirectional estimator with nonlinear WHAM equations to reconstruct and assess PMFs from relatively fast pulling trajectories. We test the method in a one dimensional model system and in a system of an antibiotic gramicidin-A (gA) channel, which is considered a significant challenge for nonequilibrium sampling. We identify key parameters for efficiently performing pulling simulations to improve and ensure the convergence and accuracy of estimated PMFs. We show that a few pulling trajectories of a relatively fast pulling speed v = 10 A/ns can return a fair estimate of the PMF of a single potassium ion in gA. PMID- 26799776 TI - New insights into reactive oxygen species and nitric oxide signalling under low oxygen in plants. AB - Plants produce reactive oxygen species (ROS) when exposed to low oxygen (O2 ). Much experimental evidence has demonstrated the existence of an oxidative burst when there is an O2 shortage. This originates at various subcellular sites. The activation of NADPH oxidase(s), in complex with other proteins, is responsible for ROS production at the plasma membrane. Another source of low O2 -dependent ROS is the mitochondrial electron transport chain, which misfunctions when low O2 limits its activity. Arabidopsis mutants impaired in proteins playing a role in ROS production display an intolerant phenotype to anoxia and submergence, suggesting a role in acclimation to stress. In rice, the presence of the submergence 1A (SUB1A) gene for submergence tolerance is associated with a higher capacity to scavenge ROS. Additionally, the destabilization of group VII ethylene responsive factors, which are involved in the direct O2 sensing mechanism, requires nitric oxide (NO). All this evidence suggests the existence of a ROS and NO - low O2 mechanism interplay which likely includes sensing, anaerobic metabolism and acclimation to stress. In this review, we summarize the most recent findings on this topic, formulating hypotheses on the basis of the latest advances. PMID- 26799780 TI - Cellulose Microfibril Formation by Surface-Tethered Cellulose Synthase Enzymes. AB - Cellulose microfibrils are pseudocrystalline arrays of cellulose chains that are synthesized by cellulose synthases. The enzymes are organized into large membrane embedded complexes in which each enzyme likely synthesizes and secretes a beta-(1 >4) glucan. The relationship between the organization of the enzymes in these complexes and cellulose crystallization has not been explored. To better understand this relationship, we used atomic force microscopy to visualize cellulose microfibril formation from nickel-film-immobilized bacterial cellulose synthase enzymes (BcsA-Bs), which in standard solution only form amorphous cellulose from monomeric BcsA-B complexes. Fourier transform infrared spectroscopy and X-ray diffraction techniques show that surface-tethered BcsA-Bs synthesize highly crystalline cellulose II in the presence of UDP-Glc, the allosteric activator cyclic-di-GMP, as well as magnesium. The cellulose II cross section/diameter and the crystal size and crystallinity depend on the surface density of tethered enzymes as well as the overall concentration of substrates. Our results provide the correlation between cellulose microfibril formation and the spatial organization of cellulose synthases. PMID- 26799778 TI - The Impact of Consumer Numeracy on the Purchase of Long-Term Care Insurance. AB - OBJECTIVE: To determine the effect of consumers' numeric abilities on the likelihood of owning private long-term care insurance. DATA SOURCE: The 2010 wave of the Health and Retirement Study, a nationally representative survey of Americans age 50 and older, was used (n = 12,796). STUDY DESIGN: Multivariate logistic regression was used to isolate the relationship between numeracy and long-term care insurance ownership. PRINCIPAL FINDINGS: Each additional question answered correctly on a numeracy scale was associated with a 13 percent increase in the likelihood of holding LTCI, after controlling for predictors of policy demand, education, and cognitive function. CONCLUSIONS: Poor numeracy may create barriers to long-term care insurance purchase. Policy efforts aimed at increasing consumer decision support or restructuring the marketplace for long-term care insurance may be needed to increase older adults' ability to prepare for future long-term care expenses. PMID- 26799781 TI - Elusive Reaction Intermediates in Solution Explored by ESI-MS: Reverse Periscope for Mechanistic Investigations. AB - Just as periscopes allow a submarine to visually search for objects above the surface of the sea, in a reversed periscope fashion electrospray mass spectrometry (ESI-MS) can analyze the compounds at the gas phase/liquid phase interface for chemical entities which may exist in solution. The challenge is the identification and structural characterization of key elusive reaction intermediates in chemical transformations, intermediates which are able to explain how chemical processes occur. This Minireview summarizes recent selected publications on the use of ESI-MS techniques for studying solution intermediates of homogeneous chemical reactions. PMID- 26799782 TI - Systematic review of dyadic and family-oriented interventions for late-life depression. AB - OBJECTIVE: Supportive behaviors (both instrumental and emotional) from spouses and close family members can impact the trajectory of older adults' depressive symptoms. Interventions that target both the patient and support person may be more effective than interventions that target the patient only, in terms of alleviating mood symptoms in the identified patient. The purpose of this paper was to review the characteristics and findings of dyadic and family-oriented interventions for late-life mood disorders to determine if they are effective and beneficial. METHODS: Following PRISMA guidelines, we conducted a systematic review of reports in the literature on dyadic or family-oriented interventions for late-life mood disorders. We searched PubMed, OVID PsycINFO, and EMBASE for peer-reviewed journal articles in English through October 2014. RESULTS: We identified 13 articles, representing a total of 10 independent investigations. Identified studies focused on spouses and close family members as support persons. Effect sizes for dyadic interventions that treated major depressive disorder were, on average, moderately strong, while effect sizes for dyadic interventions that reduced depressive symptoms were generally small. We did not identify any dyadic studies that treated bipolar disorder. CONCLUSIONS: This review showed that dyadic interventions are feasible and that these interventions can decrease symptomatology in individuals who have major depressive disorder. Research is needed to understand the relative efficacy of a dyadic approach over a single-target approach in treating depression. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26799785 TI - A new HIF-1alpha/RANTES-driven pathway to hepatocellular carcinoma mediated by germline haploinsufficiency of SART1/HAF in mice. AB - The hypoxia-inducible factor (HIF), HIF-1, is a central regulator of the response to low oxygen or inflammatory stress and plays an essential role in survival and function of immune cells. However, the mechanisms regulating nonhypoxic induction of HIF-1 remain unclear. Here, we assess the impact of germline heterozygosity of a novel, oxygen-independent ubiquitin ligase for HIF-1alpha: hypoxia-associated factor (HAF; encoded by SART1). SART1(-/-) mice were embryonic lethal, whereas male SART1(+/-) mice spontaneously recapitulated key features of nonalcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC), including steatosis, fibrosis, and inflammatory cytokine production. Male, but not female, SART1(+/-) mice showed significant up-regulation of HIF-1alpha in circulating and liver-infiltrating immune cells, but not in hepatocytes, before development of malignancy. Additionally, Kupffer cells derived from male, but not female, SART1(+/-) mice produced increased levels of the HIF-1-dependent chemokine, regulated on activation, normal T-cell expressed and secreted (RANTES), compared to wild type. This was associated with increased liver-neutrophilic infiltration, whereas infiltration of lymphocytes and macrophages were not significantly different. Neutralization of circulating RANTES decreased liver neutrophilic infiltration and attenuated HCC tumor initiation/growth in SART1(+/-) mice. CONCLUSION: This work establishes a new tumor-suppressor role for HAF in immune cell function by preventing inappropriate HIF-1 activation in male mice and identifies RANTES as a novel therapeutic target for NASH and NASH-driven HCC. PMID- 26799786 TI - Tuber proteome comparison of five potato varieties by principal component analysis. AB - BACKGROUND: Data analysis of omics data should be performed by multivariate analysis such as principal component analysis (PCA). The way data are clustered in PCA is of major importance to develop some classification systems based on multivariate analysis, such as soft independent modeling of class analogy (SIMCA). In a previous study a one-class classifier based on SIMCA was built using microarray data from a set of potatoes. The PCA grouped the transcriptomic data according to varieties. The present work aimed to use PCA to verify the clustering of the proteomic profiles for the same potato varieties. RESULTS: Proteomic profiles of five potato varieties (Biogold, Fontane, Innovator, Lady Rosetta and Maris Piper) were evaluated by two-dimensional gel electrophoresis (2 DE) performed on two immobilized pH gradient (IPG) strip lengths, 13 and 24 cm, both under pH range 4-7. For each strip length, two gels were prepared from each variety; in total there were ten gels per analysis. For 13 cm strips, 199-320 spots were detected per gel, and for 24 cm strips, 365-684 spots. CONCLUSION: All four PCAs performed with these datasets presented clear grouping of samples according to the varieties. The data presented here showed that PCA was applicable for proteomic analysis of potato and was able to separate the samples by varieties. (c) 2016 Society of Chemical Industry. PMID- 26799787 TI - Smoking during pregnancy and ADHD risk: A genetically informed, multiple-rater approach. AB - Maternal smoking during pregnancy (SDP) is a significant public health concern with adverse consequences to the health and well-being of the developing child, including behavioral outcomes such as Attention-Deficit Hyperactivity Disorder (ADHD). There is substantial interest in understanding the nature of this reported association, particularly in light of more recent genetically informed studies that suggest that the SDP-ADHD link is less clear than once thought. In a sample of families (N = 173) specifically selected for sibling pairs discordant for prenatal smoking exposure, we use a sibling-comparison approach that controls for shared genetic and familial influences to assess the effects of SDP on ADHD symptom dimensions. ADHD was measured by both parent and teacher report on the Conners report forms and the Child Behavior Checklist/Teacher Report Form (CBCL/TRF). Results for the CBCL/TRF Total ADHD score are consistent with prior genetically informed approaches and suggest that previously reported associations between SDP and ADHD are largely due to familial confounding rather than causal teratogenic effects. However, results from the Conners parent report suggest a potentially causal effect of SDP on hyperactive/impulsive and, to a lesser extent, total ADHD symptoms; SDP results in increased parent-reported hyperactive/impulsive and total ADHD symptoms even after accounting for genetic and familial confounding factors. This suggests that the Conners assessment (parent-report) may provide a sensitive measure for use in studies examining child specific SDP effects on continuous and dimensional aspects of ADHD. (c) 2016 Wiley Periodicals, Inc. PMID- 26799788 TI - The transfusion tether: Bridging the gap between end-stage hematologic malignancies and optimal end-of-life care. PMID- 26799790 TI - Platform technology to generate broadly cross-reactive antibodies to alpha helical epitopes in hemagglutinin proteins from influenza A viruses. AB - We have utilized a de novo designed two-stranded alpha-helical coiled-coil template to display conserved alpha-helical epitopes from the stem region of hemagglutinin (HA) glycoproteins of influenza A. The immunogens have all the surface-exposed residues of the native alpha-helix in the native HA protein of interest displayed on the surface of the two-stranded alpha-helical coiled-coil template. This template when used as an immunogen elicits polyclonal antibodies which bind to the alpha-helix in the native protein. We investigated the highly conserved sequence region 421-476 of HA by inserting 21 or 28 residue sequences from this region into our template. The cross-reactivity of the resulting rabbit polyclonal antibodies prepared to these immunogens was determined using a series of HA proteins from H1N1, H2N2, H3N2, H5N1, H7N7, and H7N9 virus strains which are representative of Group 1 and Group 2 virus subtypes of influenza A. Antibodies from region 449-476 were Group 1 specific. Antibodies to region 421 448 showed the greatest degree of cross-reactivity to Group 1 and Group 2 and suggested that this region has a great potential as a "universal" synthetic peptide vaccine for influenza A. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 144-159, 2016. PMID- 26799789 TI - Maternal inflammation during late pregnancy is lower in physically active compared with inactive obese women. AB - The primary purpose of this study was to compare maternal plasma inflammation between physically active and inactive obese women during late pregnancy. The secondary purpose was to examine the relationships between maternal plasma inflammation and lipid metabolism and maternal and neonatal metabolic health in these women. A cross-sectional, observational study design was performed in 16 obese-inactive (OBI; means +/- SD; age, 25.0 +/- 4.8 years; prepregnancy body mass index (BMI), 36.3 +/- 4.3 kg/m(2); body fat percentage in late gestation, 37.7% +/- 3.5%) and 16 obese-active (OBA; age, 28.9 +/- 4.8 years; prepregnancy BMI, 34.0 +/- 3.7 kg/m(2); body fat in late gestation, 36.6% +/- 3.8%) women during the third trimester of pregnancy. Maternal plasma inflammation (C reactive protein (CRP)) and insulin resistance (Homeostatic Model Assessment Insulin Resistance) were measured at rest. Plasma lipid concentration and metabolism (lipid oxidation and lipolysis) were measured at rest, during a 30-min bout of low-intensity (40% peak oxygen uptake) exercise, and during a resting recovery period using indirect calorimetry. Umbilical cord blood was collected for measurement of neonatal plasma insulin resistance, inflammation, and lipid concentration. Neonatal body composition was measured via air displacement plethysmography. Maternal plasma CRP concentration was significantly higher in OBI compared with OBA women (9.1 +/- 4.0 mg/L vs. 6.3 +/- 2.5 mg/L, p = 0.02). Maternal plasma CRP concentration was significantly associated with maternal lipolysis (r = 0.43, p = 0.02), baseline lipid oxidation rate (r = 0.39, p = 0.03), and baseline plasma free fatty acid concentration (r = 0.36, p = 0.04). In conclusion, maternal physical activity may reduce inflammation during pregnancy in obese women. Maternal lipid metabolism is related to systemic inflammation. PMID- 26799791 TI - Security giving in surrogacy motherhood process as a caring model for commissioning mothers: A theory synthesis. AB - AIM: Despite the increasing use of surrogacy, there are no caring theories/models that serve as the basis for nursing care to surrogacy commissioning mothers. This study has designed a model for caring of surrogacy commissioning mothers in 2013. METHODS: The theory synthesis of Walker and Avant's strategies of theory construction (2011) was used to design a caring model/theory. The theory synthesis includes three stages: (i) selection of focal concept (the concept of "security giving in motherhood" was selected); (ii) review of studies in order to identify factors related to focal concept relevant studies (42 articles and 13 books) were reviewed, statements and concepts related to focal concept were then extracted and classified, and their relations were specified; and (iii) organization of concepts and statements within a relevant general and effective manifestation of the phenomenon under study which led to developing of a model. RESULTS: In this caring model/theory, entitled "security giving in surrogacy motherhood", nurses roles were conceptualized within the conceptual framework that includes three main roles: (i) coordination; (ii) participation; and (iii) security giving (physical, emotional, and legal support; empowerment; presence; relationship management between both parties and advocacy). Training surrogacy specialist nurses and establishment of surrogacy care centers are important factors for implementation of the model. CONCLUSION: This model could help to provided better caring for surrogacy clients, especially for commissioning mothers. PMID- 26799792 TI - Immunohistochemical distribution of heat shock protein 70 and proliferating cell nuclear antigen in mouse placenta at different gestational stages. AB - The aim of the present study was to investigate immunohistochemical distribution of heat shock protein 70 (Hsp70) and proliferating cell nuclear antigen (PCNA) in the mouse placenta at different gestational stages. For this purpose a total of 18 Swiss albino female mice at 12-14 weeks of age were used. Females were sacrificed on days 3 (early), 10 (mid-), and 17 (late) of pregnancy and the implantation sites of the pregnant uterus were sampled. The sections were made transversely through the central region of the implantation site and stained with hematoxylin and eosin for histological examination. PCNA and Hsp70 was stained immunohistochemically. Since the definitive placenta was not still formed on day 3 of pregnancy, Hsp70 and PCNA positivity were evaluated in only luminal epithelium and decidual-stromal cells. On days 10 and 17 of pregnancy, Hsp70 and PCNA positivity were evaluated in labyrinth zone, junctional zone and decidual layer of placenta. Hsp70 expression was observed trophoblast cells and decidual cells and was relatively constant throughout the pregnancy. This protein was strongly labeled in the trophoblast cells; while decidual cells were displayed moderate staining. In early pregnant mouse uteri, PCNA was mainly localized in decidual-stromal cells. The trophoblast cells and decidual cells displayed highly proliferative activity at the midgestational period. However there was a significant decrease in the percentage of PCNA positive cells in late gestation. PMID- 26799793 TI - Engineering Digestion: Multiscale Processes of Food Digestion. AB - Food digestion is a complex, multiscale process that has recently become of interest to the food industry due to the developing links between food and health or disease. Food digestion can be studied by using either in vitro or in vivo models, each having certain advantages or disadvantages. The recent interest in food digestion has resulted in a large number of studies in this area, yet few have provided an in-depth, quantitative description of digestion processes. To provide a framework to develop these quantitative comparisons, a summary is given here between digestion processes and parallel unit operations in the food and chemical industry. Characterization parameters and phenomena are suggested for each step of digestion. In addition to the quantitative characterization of digestion processes, the multiscale aspect of digestion must also be considered. In both food systems and the gastrointestinal tract, multiple length scales are involved in food breakdown, mixing, absorption. These different length scales influence digestion processes independently as well as through interrelated mechanisms. To facilitate optimized development of functional food products, a multiscale, engineering approach may be taken to describe food digestion processes. A framework for this approach is described in this review, as well as examples that demonstrate the importance of process characterization as well as the multiple, interrelated length scales in the digestion process. PMID- 26799794 TI - Resveratrol Protects against TNF-alpha-Induced Injury in Human Umbilical Endothelial Cells through Promoting Sirtuin-1-Induced Repression of NF-KB and p38 MAPK. AB - Inflammation and reactive oxygen species (ROS) play important roles in the pathogenesis of atherosclerosis. Resveratrol has been shown to possess anti inflammatory and antioxidative stress activities, but the underlying mechanisms are not fully understood. In the present study, we investigated the molecular basis associated with the protective effects of resveratrol on tumor necrosis factor-alpha (TNF-alpha)-induced injury in human umbilical endothelial cells (HUVECs) using a variety of approaches including a cell viability assay, reverse transcription and quantitative polymerase chain reaction, western blot, and immunofluorescence staining. We showed that TNF-alpha induced CD40 expression and ROS production in cultured HUVECs, which were attenuated by resveratrol treatment. Also, resveratrol increased the expression of sirtuin 1 (SIRT1); and repression of SIRT1 by small-interfering RNA (siRNA) and the SIRT1 inhibitor Ex527 reduced the inhibitory effects of resveratrol on CD40 expression and ROS generation. In addition, resveratrol downregulated the levels of p65 and phospho p38 MAPK, but this inhibitory effect was attenuated by the suppression of SIRT1 activity. Moreover, the p38 MAPK inhibitor SD203580 and the nuclear factor (NF) kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) achieved similar repressive effects as resveratrol on TNF-alpha-induced ROS generation and CD40 expression. Thus, our study provides a mechanistic link between resveratrol and the activation of SIRT1, the latter of which is involved in resveratrol-mediated repression of the p38 MAPK/NF-kappaB pathway and ROS production in TNF-alpha treated HUVECs. PMID- 26799795 TI - NeuroKinect: A Novel Low-Cost 3Dvideo-EEG System for Epileptic Seizure Motion Quantification. AB - Epilepsy is a common neurological disorder which affects 0.5-1% of the world population. Its diagnosis relies both on Electroencephalogram (EEG) findings and characteristic seizure-induced body movements--called seizure semiology. Thus, synchronous EEG and (2D)video recording systems (known as Video-EEG) are the most accurate tools for epilepsy diagnosis. Despite the establishment of several quantitative methods for EEG analysis, seizure semiology is still analyzed by visual inspection, based on epileptologists' subjective interpretation of the movements of interest (MOIs) that occur during recorded seizures. In this contribution, we present NeuroKinect, a low-cost, easy to setup and operate solution for a novel 3Dvideo-EEG system. It is based on a RGB-D sensor (Microsoft Kinect camera) and performs 24/7 monitoring of an Epilepsy Monitoring Unit (EMU) bed. It does not require the attachment of any reflectors or sensors to the patient's body and has a very low maintenance load. To evaluate its performance and usability, we mounted a state-of-the-art 6-camera motion-capture system and our low-cost solution over the same EMU bed. A comparative study of seizure simulated MOIs showed an average correlation of the resulting 3D motion trajectories of 84.2%. Then, we used our system on the routine of an EMU and collected 9 different seizures where we could perform 3D kinematic analysis of 42 MOIs arising from the temporal (TLE) (n = 19) and extratemporal (ETE) brain regions (n = 23). The obtained results showed that movement displacement and movement extent discriminated both seizure MOI groups with statistically significant levels (mean = 0.15 m vs. 0.44 m, p<0.001; mean = 0.068 m(3) vs. 0.14 m(3), p<0.05, respectively). Furthermore, TLE MOIs were significantly shorter than ETE (mean = 23 seconds vs 35 seconds, p<0.01) and presented higher jerking levels (mean = 345 ms(-3) vs 172 ms(-3), p<0.05). Our newly implemented 3D approach is faster by 87.5% in extracting body motion trajectories when compared to a 2D frame by frame tracking procedure. We conclude that this new approach provides a more comfortable (both for patients and clinical professionals), simpler, faster and lower-cost procedure than previous approaches, therefore providing a reliable tool to quantitatively analyze MOI patterns of epileptic seizures in the routine of EMUs around the world. We hope this study encourages other EMUs to adopt similar approaches so that more quantitative information is used to improve epilepsy diagnosis. PMID- 26799796 TI - Antimelanogenic activity of MHY384 via inhibition of NO-induced cGMP signalling. PMID- 26799798 TI - Women at low risk for breast cancer recurrence can avoid chemotherapy: Initial trial findings support current practices. PMID- 26799799 TI - Prenatal exposure to maternal cancer with or without treatment does not impair child development. PMID- 26799800 TI - Breast cancer incidence and death increasing in less-developed countries. PMID- 26799801 TI - Dahlstrom KR, Li G, Hussey CS, Vo JT, Wei Q, Zhao C S and Sturgis EM. Circulating human papillomavirus DNA as a marker for disease extent and recurrence among patients with oropharyngeal cancer. Cancer. 2015;121:3455-3464. PMID- 26799802 TI - Household concentrations and personal exposure of PM2.5 among urban residents using different cooking fuels. AB - Exposure to PM2.5 is a leading environmental risk factor for many diseases and premature deaths, arousing growing public concerns. In this study, indoor and outdoor PM2.5 concentrations were investigated during the heating and non-heating seasons in an urban area in northwest China. Personal inhalation exposure levels among different age groups were evaluated, and the difference attributable to different cooking fuels including coal, gas and electricity, was discussed. The average concentrations of PM2.5 in the kitchen and the bedroom were 125+/-51 and 119+/-64MUg/m(3) during the heating season, and 80+/-67 and 80+/-50MUg/m(3) during the non-heating season, respectively. Indoor PM2.5, from indoor combustion sources but also outdoor penetration, contributed to about 75% of the total PM2.5 exposure. Much higher indoor concentrations and inhalation exposure levels were found in households using coal for cooking compared to those using gas and electricity. Changing from coal to gas or electricity for cooking could result in a reduction of PM2.5 in the kitchen by 40-70% and consequently lower inhalation exposure levels, especially for children and women. PMID- 26799803 TI - Insights into the mechanisms underlying mercury-induced oxidative stress in gills of wild fish (Liza aurata) combining (1)H NMR metabolomics and conventional biochemical assays. AB - Oxidative stress has been described as a key pathway to initiate mercury (Hg) toxicity in fish. However, the mechanisms underlying Hg-induced oxidative stress in fish still need to be clarified. To this aim, environmental metabolomics in combination with a battery of conventional oxidative stress biomarkers were applied to the gills of golden grey mullet (Liza aurata) collected from Largo do Laranjo (LAR), a confined Hg contaminated area, and Sao Jacinto (SJ), selected as reference site (Aveiro Lagoon, Portugal). Higher accumulation of inorganic Hg and methylmercury was found in gills of fish from LAR relative to SJ. Nuclear magnetic resonance (NMR)-based metabolomics revealed changes in metabolites related to antioxidant protection, namely depletion of reduced glutathione (GSH) and its constituent amino acids, glutamate and glycine. The interference of Hg with the antioxidant protection of gills was corroborated through oxidative stress endpoints, namely the depletion of glutathione peroxidase and superoxide dismutase activities at LAR. The increase of total glutathione content (reduced glutathione+oxidized glutathione) at LAR, in parallel with GSH depletion aforementioned, indicates the occurrence of massive GSH oxidation under Hg stress, and an inability to carry out its regeneration (glutathione reductase activity was unaltered) or de novo synthesis. Nevertheless, the results suggest the occurrence of alternative mechanisms for preventing lipid peroxidative damage, which may be associated with the enhancement of membrane stabilization/repair processes resulting from depletion in the precursors of phosphatidylcholine (phosphocholine and glycerophosphocholine), as highlighted by NMR spectroscopy. However, the observed decrease in taurine may be attributable to alterations in the structure of cell membranes or interference in osmoregulatory processes. Overall, the novel concurrent use of metabolomics and conventional oxidative stress endpoints demonstrated to be sensitive and effective towards a mechanistically based assessment of Hg toxicity in gills of wild fish, providing new insights into the toxicological pathways underlying the oxidative stress. PMID- 26799804 TI - Using ecosystem services in decision-making to support sustainable development: Critiques, model development, a case study, and perspectives. AB - In this paper, I propose a general, consistent, and operational approach that accounts for ecosystem services in a decision-making context: I link ecosystem services to sustainable development criteria; adopt multi-criteria analysis to measure ecosystem services, with weights provided by stakeholders used to account for equity issues; apply both temporal and spatial discount rates; and adopt a technique to order performance of the possible solutions based on their similarity to an ideal solution (TOPSIS) to account for uncertainty about the parameters and functions. Applying this approach in a case study of an offshore research platform in Italy (CNR Acqua Alta) revealed that decisions depend non linearly on the degree of loss aversion, to a smaller extent on a global focus (as opposed to a local focus), and to the smallest extent on social concerns (as opposed to economic or environmental concerns). Application of the general model to the case study leads to the conclusion that the ecosystem services framework is likely to be less useful in supporting decisions than in identifying the crucial features on which decisions depend, unless experts from different disciplines are involved, stakeholders are represented, and experts and stakeholders achieve mutual understanding. PMID- 26799805 TI - Human exposure to thallium through tap water: A study from Valdicastello Carducci and Pietrasanta (northern Tuscany, Italy). AB - A geological study evidenced the presence of thallium (Tl) at concentrations of concern in groundwaters near Valdicastello Carducci (Tuscany, Italy). The source of contamination has been identified in the Tl-bearing pyrite ores occurring in the abandoned mining sites of the area. The strongly acidic internal waters flowing in the mining tunnels can reach exceptional Tl concentrations, up to 9000MUg/L. In September 2014 Tl contamination was also found in the tap water distributed in the same area (from 2 to 10MUg/L). On October 3, 2014 the local authorities imposed a Do Not Drink order to the population. Here we report the results of the exposure study carried out from October 2014 to October 2015, and aimed at quantifying Tl levels in 150 urine and 318 hair samples from the population of Valdicastello Carducci and Pietrasanta. Thallium was quantified by inductively coupled plasma - mass spectrometry (ICP-MS). Urine and hair were chosen as model matrices indicative of different time periods of exposure (short term and long-term, respectively). Thallium values found in biological samples were correlated with Tl concentrations found in tap water in the living area of each citizen, and with his/her habits. Thallium concentration range found in hair and urine was 1-498ng/g (values in unexposed subjects 0.1-6ng/g) and 0.046 5.44MUg/L (reference value for the European population 0.006MUg/L), respectively. Results show that Tl levels in biological samples were significantly associated with residency in zones containing elevated water Tl levels. The kinetics of decay of Tl concentration in urine samples was also investigated. At the best of our knowledge, this is the first study on human contamination by Tl through water involving such a high number of samples. PMID- 26799806 TI - Spatial analysis and source profiling of beta-agonists and sulfonamides in Langat River basin, Malaysia. AB - Beta-agonists and sulfonamides are widely used for treating both humans and livestock for bronchial and cardiac problems, infectious disease and even as growth promoters. There are concerns about their potential environmental impacts, such as producing drug resistance in bacteria. This study focused on their spatial distribution in surface water and the identification of pollution sources in the Langat River basin, which is one of the most urbanized watersheds in Malaysia. Fourteen beta-agonists and 12 sulfonamides were quantitatively analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A geographic information system (GIS) was used to visualize catchment areas of the sampling points, and source profiling was conducted to identify the pollution sources based on a correlation between a daily pollutant load of the detected contaminant and an estimated density of human or livestock population in the catchment areas. As a result, 6 compounds (salbutamol, sulfadiazine, sulfapyridine, sulfamethazine, sulfadimethoxine and sulfamethoxazole) were widely detected in mid catchment areas towards estuary. The source profiling indicated that the pollution sources of salbutamol and sulfamethoxazole were from sewage, while sulfadiazine was from effluents of cattle, goat and sheep farms. Thus, this combination method of quantitative and spatial analysis clarified the spatial distribution of these drugs and assisted for identifying the pollution sources. PMID- 26799807 TI - Bacterial production and their role in the removal of dissolved organic matter from tributaries of drinking water reservoirs. AB - Enhanced concentrations of dissolved organic matter (DOM) in freshwaters are an increasing problem in drinking water reservoirs. In this study we investigated bacterial DOM degradation rates in the tributaries of the reservoirs and tested the hypotheses that (1) DOM degradation is high enough to decrease DOM loads to reservoirs considerably, (2) DOM degradation is affected by stream hydrology, and (3) phosphorus addition may stimulate bacterial DOM degradation. Bacterial biomass production, which was used as a measure of DOM degradation, was highest in summer, and was usually lower at upstream than at downstream sites. An important proportion of bacterial production was realized in epilithic biofilms. Production of planktonic and biofilm bacteria was related to water temperature. Planktonic production weakly correlated to DOM quality and to total phosphorus concentration. Addition of soluble reactive phosphorus did not stimulate bacterial DOM degradation. Overall, DOM was considerably degraded in summer at low discharge levels, whereas degradation was negligible during flood events (when DOM load in reservoirs was high). The ratio of DOM degradation to total DOM release was negatively related to discharge. On annual average, only 0.6-12% of total DOM released by the catchments was degraded within the tributaries. PMID- 26799808 TI - Increases in the climate change adaption effectiveness and availability of vegetation across a coastal to desert climate gradient in metropolitan Los Angeles, CA, USA. AB - Urbanization has increased heat in the urban environment, with many consequences for human health and well-being. Managing climate change in part through increasing vegetation is desired by many cities to mitigate current and future heat related issues. However, little information is available on what influences the current effectiveness and availability of vegetation for local cooling. In this study, we identified the variation in the interacting relationships among vegetation (normalized difference vegetation index), socioeconomic status (neighborhood income), elevation and land surface temperature (LST) to identify how vegetation based surface cooling services change throughout the pronounced coastal to desert climate gradient of the Los Angeles, CA metropolitan region, a megacity of >18 million residents. A key challenge for understanding variation in vegetation as a climate change adaptation tool spanning neighborhood to megacity scales is developing new "big data" analytical tools. We used structural equation modeling (SEM) to quantify the interacting relationships among socio-economic status data obtained from government census data, elevation and new LST and vegetation data obtained from an airborne imaging campaign conducted in 2013 for the urban and suburban areas across a series of fifteen climate zones. Vegetation systematically increased in cooling effectiveness from 6.06 to 31.77 degrees with increasing distance from the coast. Vegetation and neighborhood income were positively correlated throughout all climate zones with a peak in the relationship occurring near 25km from the coast. Because of the interaction between these two relationships, we also found that higher income neighborhoods were cooler and that this effect peaked at about 30km from the coast. These results show the availability and effectiveness of vegetation on the local climate varies tremendously throughout the Los Angeles, CA metropolitan area. Further, using the more inland climate zones as future analogs for more coastal zones, suggests that in the warmer climate conditions projected for the region the effectiveness of vegetation for regional cooling may increase thus acting as a localized negative feedback mechanism. PMID- 26799809 TI - Evaluation of a microwave based reactor for the treatment of blackwater sludge. AB - A laboratory-scale microwave (MW) unit was applied to treat fresh blackwater sludge that represented fecal sludge (FS) produced at heavily used toilet facilities. The sludge was exposed to MW irradiation at different power levels and for various durations. Variables such as sludge volume and pathogen reduction were observed. The results demonstrated that the MW is a rapid and efficient technology that can reduce the sludge volume by over 70% in these experimental conditions. The concentration of bacterial pathogenic indicator E. coli also decreased to below the analytical detection levels. Furthermore, the results indicated that the MW operational conditions including radiation power and contact time can be varied to achieve the desired sludge volume and pathogen reduction. MW technology can be further explored for the potential scaling-up as an option for rapid treatment of FS from intensively used sanitation facilities such as in emergency situations. PMID- 26799811 TI - Cross-Metathesis of Bronsted Acid Masked Alkenylamines with Acrylates for the Synthesis of Polyamide Monomers. AB - Ruthenium-alkylidene-catalyzed cross-metathesis of a range of homologous alkenylamine salts provides expedient and high-yielding routes to commercially valuable polyamide monomers using a single catalyst, telescopic workup, and mild experimental conditions. PMID- 26799810 TI - Planning for climate change: The need for mechanistic systems-based approaches to study climate change impacts on diarrheal diseases. AB - Increased precipitation and temperature variability as well as extreme events related to climate change are predicted to affect the availability and quality of water globally. Already heavily burdened with diarrheal diseases due to poor access to water, sanitation and hygiene facilities, communities throughout the developing world lack the adaptive capacity to sufficiently respond to the additional adversity caused by climate change. Studies suggest that diarrhea rates are positively correlated with increased temperature, and show a complex relationship with precipitation. Although climate change will likely increase rates of diarrheal diseases on average, there is a poor mechanistic understanding of the underlying disease transmission processes and substantial uncertainty surrounding current estimates. This makes it difficult to recommend appropriate adaptation strategies. We review the relevant climate-related mechanisms behind transmission of diarrheal disease pathogens and argue that systems-based mechanistic approaches incorporating human, engineered and environmental components are urgently needed. We then review successful systems-based approaches used in other environmental health fields and detail one modeling framework to predict climate change impacts on diarrheal diseases and design adaptation strategies. PMID- 26799812 TI - Caries-Preventive Effect of High-Viscosity Glass Ionomer and Resin-Based Fissure Sealants on Permanent Teeth: A Systematic Review of Clinical Trials. AB - BACKGROUND: Glass-ionomers are traditionally regarded to be inferior to resin as fissure sealants in protecting teeth from dental caries, due to their comparatively lower retention rate. Unlike low-viscosity glass-ionomers, high viscosity glass-ionomer cements (HVGIC) are placed as sealants by pressing the material into pits and fissures with a petroleum-jelly-coated index finger. Hence, HVGIC sealants are assumed to penetrate pits and fissures deeper, resulting in a higher material retention rate, which may increase its caries preventive effect. METHODS: The aim of this review was to answer the question as to whether, in patients with fully erupted permanent molar teeth, HVGIC based fissure sealants are less effective to protect against dental carious lesions in occlusal pits and fissures than resin-based fissure sealants? A systematic literature search in eight databases was conducted. Heterogeneity of accepted trials and imprecision of the established evidence were assessed. Extracted sufficiently homogenous datasets were pooled by use of a random-effects meta analysis. Internal trial validity was evaluated. The protocol of this systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO / Nr.: CRD42015016007). RESULTS: Seven clinical trials were provisionally included for further review. Of these, one was excluded. Seven trial reports reporting on six trials were accepted. From these, 11 datasets were extracted and pooled in four meta-analyses. The results suggest no statistically significant differences after up to 48 months and borderline significant differences in favour of HVGIC sealants after 60 months (RR 0.29; 95% CI: 0.09 0.95; p = 0.04 / RD -0.07; 95% CI: -0.14, -0.01). The point estimates and upper confidence levels after 24, 36, 48 and 60 months of RR 1.36; RR 0.90; RR 0.62; RR 0.29 and 2.78; 1.67; 1.21; 0.95, respectively, further suggest a chronological trend in favour of HVGIC above resin-based sealants. The internal trial validity was judged to be low and the bias risk high for all trials. Imprecision of results was considered too high for clinical guidance. CONCLUSION: It can be concluded that: (i) Inferiority claims against HVGIC in comparison to resin-based sealants as current gold-standard are not supported by the clinical evidence; (ii) The clinical evidence suggests similar caries-preventive efficacy of HVGIC and resin-based sealants after a period of 48 months in permanent molar teeth but remains challenged by high bias risk; (iii) Evidence concerning a possible superiority of HVGIC above resin-based sealants after 60 months is poor (even if the high bias risk is disregarded) due to imprecision and requires corroboration through future research. PMID- 26799813 TI - Gender-related similarities and differences in the body distribution of grape seed flavanols in rats. AB - SCOPE: Dietary flavanols produce beneficial health effects, and once absorbed, they are recognized as xenobiotics and undergo phase-II enzymatic detoxification. Flavanols health-promoting properties are mainly attributed to their metabolic products. This work aimed to elucidate whether rats of the opposite sex exhibited differences in the metabolism and distribution of ingested flavanols. METHODS AND RESULTS: Acute doses of grape seed polyphenols were administered to male and female rats. After 1, 2 and 4 h, plasma, liver, mesenteric white adipose tissue (MWAT), brain and hypothalamus flavanol metabolites were quantified by HPLC MS/MS. Results indicated important sex-related quantitative differences in plasma and brain. Moreover, remarkable sex-related differences in the distributions and types of flavanol metabolites were also observed between liver and brain. CONCLUSIONS: This study demonstrated that sex differentially influences the metabolism and distribution of flavanols throughout the bodies of rats, which may affect the physiological bioactivities of flavanols between males and females. PMID- 26799814 TI - Association between tooth loss and medical costs related to stroke in healthy older adults aged over 75 years in Japan. AB - AIM: Growing evidence suggests that tooth loss is associated with increased risk of stroke. In the current study, we investigated cumulative medical costs related to stroke using data from the Advanced Elderly Medical Service System. We hypothesized that tooth loss was associated with an increase in medical costs related to stroke among older Japanese adults. METHODS: A total of 273 Japanese adults aged 80 years were enrolled in the current study. Baseline medical and dental examinations were carried out in June 2008. Medical care use and costs were monitored by linkage with National Health Insurance claim files from baseline to the end of February 2011. Medical costs related to stroke per month were calculated and examined for any association with the baseline number of remaining teeth using a linear regression model with robust standard errors. RESULTS: A total of 19 individuals were admitted to hospital for stroke during the follow-up period. A significant negative association was found between the number of teeth and medical costs related to stroke per month. The regression coefficients of the number of teeth in relation to medical costs related to stroke was -248 (95% CI -438 to -58, P = 0.011) in the crude model and -226 (95% CI -413 to -38, P = 0.018) after adjusting for other confounders. CONCLUSION: Within the limitations of the present study, the reported findings suggest an independent relationship of tooth loss with increase in medical cost related to stroke among older Japanese adults. Further studies are necessary to substantiate these findings. Geriatr Gerontol Int 2017; 17: 202-210. PMID- 26799815 TI - Can Ingestion of Lead Shot and Poisons Change Population Trends of Three European Birds: Grey Partridge, Common Buzzard, and Red Kite? AB - Little is known about the magnitude of the effects of lead shot ingestion alone or combined with poisons (e.g., in bait or seeds/granules containing pesticides) on population size, growth, and extinction of non-waterbird avian species that ingest these substances. We used population models to create example scenarios demonstrating how changes in these parameters might affect three susceptible species: grey partridge (Perdix perdix), common buzzard (Buteo buteo), and red kite (Milvus milvus). We added or subtracted estimates of mortality due to lead shot ingestion (4-16% of mortality, depending on species) and poisons (4-46% of mortality) reported in the UK or France to observed mortality of studied populations after models were calibrated to observed population trends. Observed trends were decreasing for partridge (in continental Europe), stable for buzzard (in Germany), and increasing for red kite (in Wales). Although lead shot ingestion and poison at modeled levels did not change the trend direction for the three species, they reduced population size and slowed population growth. Lead shot ingestion at modeled rates reduced population size of partridges by 10%, and when combined with bait and pesticide poisons, by 18%. For buzzards, decrease in mean population size by lead shot and poisons combined was much smaller (<= 1%). The red kite population has been recovering; however, modeled lead shot ingestion reduced its annual growth rate from 6.5% to 4%, slowing recovery. If mortality from poisoned baits could be removed, the kite population could potentially increase at a rapid annual rate of 12%. The effects are somewhat higher if ingestion of these substances additionally causes sublethal reproductive impairment. These results have uncertainty but suggest that declining or recovering populations are most sensitive to lead shot or poison ingestion, and removal of poisoned baits can have a positive impact on recovering raptor populations that frequently feed on carrion. PMID- 26799817 TI - Studies on the antioxidant properties of some phytoestrogens. AB - Isoflavones genistein and daidzein are nonsteroidal phytoestrogens occurring mainly in soybean foods. These phytoestrogens possess estrogenic properties and show a variety of health benefits as anti-inflammatory agents. However, the mechanism of their action has not been identified in detail. The aim of this study is to characterize the antioxidant powers of genistein, daidzein and daidzein metabolite-equol through their activities to scavenge superoxide anion radical (O(*) 2 (-) ), hydroxyl radical (HO(*) ), 2,2-diphenyl-1-picrylhydrazyl radical (DPPH(*) ) and hydrogen peroxide (H2 O2 ) using chemiluminescence and spectrophotometry techniques. Potassium superoxide in dimethyl sulphoxide (DMSO) and 18-crown-6 ether were used as a source of O(*) 2 (-) . Hydroxyl radicals were produced using the Fenton reaction. In free radical assays, genistein had the IC50 values (an amount of antioxidant concentration required to decrease the initial radical concentration by 50%) 0.391 +/- 0.012 mM for O(*) 2 (-) , 0.621 +/- 0.028 mM for HO(*) and 1.89 +/- 0.16 mM for DPPH(*) . The IC50 values for daidzein for these free radicals were 1.924 +/- 0.011 mM, 0.702 +/- 0.012 mM and 2.81 +/- 0.03 mM, respectively. Equol was the most active the free radical scavenger with IC50 = 0.451 +/- 0.018 mM for HO(*) and IC50 = 1.36 +/- 0.11 mM for DPPH(*) . All tested compounds exerted a significant effect on the H2 O2 : IC50 = 18.1 +/- 1.1 MUM for genistein, IC50 = 2.1 +/- 0.5 MUM for daidzein, and IC50 = 1.06 +/- 0.2 MUM for equol. These findings show that genistein, daidzein and equol are effective free radical scavengers and possess high antioxidant power in vitro. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26799819 TI - Primary care experiences of people who live with chronic pain and receive opioids to manage pain: A qualitative methodology. AB - BACKGROUND AND PURPOSE: The prevalence of chronic pain continues to rise and the majority of patients with chronic pain are managed in primary care. The purpose of this research was to provide the perspectives of patients who live with chronic pain and receive opioids to help manage their pain from primary care. METHODS: In this qualitative study, 12 participants from a Midwest primary care clinic described their primary care experiences with receiving opioids for chronic pain. Thematic and interpretive analyses were used to understand the issues. CONCLUSIONS: Participants receiving opioids for pain management through primary care feared losing access to opioids, wanted to protect sobriety when they had histories of substance use disorder, experienced stress at their jobs with frequent appointments, identified inconsistencies in health care prolonging their suffering and increasing substance misuse, and identified improvement in coping with pain when they had confidence in healthcare providers. IMPLICATIONS FOR PRACTICE: Providing patient-centered care while managing patients with pain and unknown risk for prescription opioid misuse is possible. Understanding influences that create prescription opioid risk for misuse can help nurse practitioners improve their delivery of care by providing consistent and convenient healthcare encounters, and help patients protect themselves from risk of prescription opioid misuse. PMID- 26799820 TI - Goblet cell density and distribution in cats with clinically and histologically normal conjunctiva. AB - OBJECTIVE: The aim of this study was to evaluate goblet cell density (GCD) and distribution in cats without clinical evidence of ocular surface disease and without histologic evidence of conjunctival disease. ANIMALS STUDIED: Fourteen Domestic Shorthair cats euthanized for reasons unrelated to this study. PROCEDURES: Before euthanasia, cats were verified using slit-lamp biomicroscopy and fluorescein staining to be free of eyelid or ocular surface abnormalities. Immediately after euthanasia, bilateral conjunctival specimens including third eyelid (TEL) were collected, routinely processed, and stained with periodic acid Schiff and hematoxylin and eosin. Thirteen conjunctival regions were identified. For each region, GCD was expressed as the percentage of goblet cells/200 basal epithelial cells. RESULTS: Mean GCD ranged widely by region: anterior surface of the TEL = 48.8%, fornicial regions = 47.0%, palpebral regions = 38.5%, bulbar regions = 19.6%, and posterior surface of the TEL = 12.6%. The anterior surface of the TEL had significantly higher GCD than did the bulbar and the palpebral regions, but not the fornicial regions. Bulbar conjunctiva had significantly lower GCD than did all other conjunctival regions except the posterior surface of the TEL. No significant difference was noted between GCD of male versus female cats, dorsal versus ventral regions, or lateral versus medial regions. CONCLUSIONS: Although conjunctival GCD ranged widely by region, the anterior surface of the TEL appears to be an excellent location for assessing conjunctival goblet cells in cats because this area has high GCD and is more readily accessible than is the palpebral, fornicial, or bulbar conjunctiva. PMID- 26799821 TI - The epidemiology of hospitalised acute kidney injury not requiring dialysis in England from 1998 to 2013: retrospective analysis of hospital episode statistics. AB - AIMS: Epidemiology studies of acute kidney injury (AKI) have focused on cases requiring dialysis but those not requiring dialysis represent the majority. To address this gap, we interrogated hospital episode statistics (HES) to investigate population trends in temporal epidemiology of AKI not requiring dialysis between 1998 and 2013. METHODOLOGY: In this retrospective observational study of HES data covering the entire English National Health Service, we identified 1,136,167 AKI events, not requiring dialysis, diagnosed between 1998 and 2013. We explored the effect of age, gender, ethnicity, Charlson's comorbidity score (CCS), method of admission, diagnosis period and AKI in diagnosis codes on temporal changes in the incidence and case-fatality of AKI with specific examination of its predictors. RESULT: The incidence of AKI increased from 15,463 cases (317 pmp) in 1998-1999 to 213,700 cases (3995 pmp) in 2012-2013. There was increase in proportion of people over 75 years from 51.1% in 1998-1999 to 63.4% in 2012-2013. Overall unadjusted case-fatality decreased from 42.3% in 1998-2003 to 27.1% in 2008-2013, p < 0.001. Compared with 1998-2003, the multivariable adjusted odds ratio for death was 0.64 in 2003-2008 (95% CI 0.63 0.65) and 0.35 in 2008-2013 (95% CI 0.34-0.35). Odds for death were higher for patients over 85 years (2.93; 95% CI 2.89-2.97), CCS of more than five (2.75; 95% CI 2.71-2.79), emergency admissions (2.14; 95% CI 2.09-2.18) and AKI in the secondary diagnosis code (1.35; 95% CI 1.33-1.36) and AKI in other diagnoses codes (2.17; 95% CI 2.15-2.20). CONCLUSIONS: In England, the incidence of AKI not requiring dialysis has increased and case-fatality has decreased over last 15 years. Efforts to reduce the incidence of AKI and improve survival should focus on elderly people, emergency admissions and those with multi-morbidity. PMID- 26799823 TI - PTSD Symptom Trajectories in Disaster Volunteers: The Role of Self-Efficacy, Social Acknowledgement, and Tasks Carried Out. AB - Millions of volunteers respond after disasters, with a 24% to 46% risk of developing posttraumatic stress disorder (PTSD). It is unclear which symptom trajectories develop and how they differ between core (volunteering before the disaster) and noncore volunteers (joining after the disaster) and which factors predict trajectories. Symptoms of PTSD were assessed at 6-, 12-, and 18-months postearthquake in 449 volunteers in Indonesia. Demographics, previous mental health service use, self-efficacy, social acknowledgment, and type of tasks were assessed at 6 months. In both core and noncore volunteers, 2 PTSD symptom trajectories emerged: a resilient trajectory (moderate levels of symptoms with a slow decrease over time; 90.9%) and a chronic trajectory (higher levels of symptoms with an increase over time; 9.1%). In both trajectories, core volunteers had fewer symptoms than noncore volunteers. Core volunteers in the chronic trajectory were characterized by having sought prior mental help, reported lower levels of self-efficacy and social acknowledgment, and were more likely to have provided psychosocial support to beneficiaries (Cramer's V = .17 to .27, partial eta(2) = .02 to .06). Aid organizations should identify and follow up chronic PTSD trajectories in volunteers, including the noncore, who may be out of sight to the organization after the acute response phase. PMID- 26799824 TI - Total Synthesis of Ileabethoxazole, Pseudopteroxazole, and seco Pseudopteroxazole. AB - The total syntheses of ileabethoxazole, pseudopteroxazole, and seco pseudopteroxazole, three antituberculosis diterpenoids that had been isolated from Pseudopterogorgia elisabethae, were accomplished in a collective fashion. A cascade alkyne carbopalladation/Stille reaction was exploited to construct a triene precursor with suitable geometry. A fully substituted arene was then assembled through a key 6pi electrocyclization/aromatization sequence, and served as an advanced common intermediate. Two radical cyclizations led to the formation of the five- and six-membered rings of ileabethoxazole and pseudopteroxazole, respectively, with the desired stereochemistry, and a straightforward side-chain elongation delivered seco-pseudopteroxazole. PMID- 26799826 TI - Emulsion Templating Cyclic Polymers as Microscopic Particles with Tunable Porous Morphology. AB - Cyclic polymers are a particular class of macromolecules without terminal groups. Most studies has involved their physical properties and polymer composition, while attention has rarely been paid to their emulsification in an oil-water system. Herein we synthesized a cyclic polymer with polystyrene side chains via ring-expansion metathesis polymerization and click-chemistry. This cyclic polymer was compared with linear polystyrene in order to investigate the effect of cyclic topology on preparing porous particles by emulsion templating methods. The contribution of cyclic topology to emulsification originates from the formation of hollow microspheres with the use of cyclic polymer while linear polymer only afforded solid microspheres. With addition of hexadecane as soft template, both cyclic polymer and linear polymer emulsions were successfully converted into porous particles. Superior to linear polymer, cyclic polymer enables the stabilization of emulsion droplets and the tuning of porous morphology. It is revealed that cyclic polymer with nanoring shape tends to assemble at the interfacial area, leading to the Pickering effect that decelerates the macrophase separation. Furthermore, the unique porous feature of polymer particles affords a convenient application for the detection of trace explosive. PMID- 26799827 TI - The Species and Origin of Shark Fins in Taiwan's Fishing Ports, Markets, and Customs Detention: A DNA Barcoding Analysis. AB - The increasing consumption of shark products, along with the shark's fishing vulnerabilities, has led to the decrease in certain shark populations. In this study we used a DNA barcoding method to identify the species of shark landings at fishing ports, shark fin products in retail stores, and shark fins detained by Taiwan customs. In total we identified 23, 24, and 14 species from 231 fishing landings, 316 fin products, and 113 detained shark fins, respectively. All the three sample sources were dominated by Prionace glauca, which accounted for more than 30% of the collected samples. Over 60% of the species identified in the fin products also appeared in the port landings, suggesting the domestic-dominance of shark fin products in Taiwan. However, international trade also contributes a certain proportion of the fin product markets, as four species identified from the shark fin products are not found in Taiwan's waters, and some domestic available species were also found in the customs-detained sample. In addition to the species identification, we also found geographical differentiation in the cox1 gene of the common thresher sharks (Alopias vulpinus), the pelagic thresher shark (A. pelagicus), the smooth hammerhead shark (Sphyrna zygaena), and the scalloped hammerhead shark (S. lewini). This result might allow fishing authorities to more effectively trace the origins as well as enforce the management and conservation of these sharks. PMID- 26799829 TI - What role does the general practitioner in France play among cancer patients during the initial treatment phase with intravenous chemotherapy? A qualitative study. AB - BACKGROUND: France's ethical and legal principles place general practitioners (GPs) at the forefront of cancer patient management, coordination, and follow-up. The objective of this study was to determine the actual role of GPs in the follow up phase as well as patient perspectives on their GPs. METHOD: A multidisciplinary group of researchers conducted this qualitative study based on in-depth interviews of 50 patients managed at two cancer centres. A content analysis method was used to analyse the study data. RESULTS: According to the patients interviewed for this study, their GPs were relatively ineffective at managing medical problems related to cancer by comparison with their oncologists. Nonetheless, the patients had all consulted their GPs during the interval between the diagnosis and our interview. Reasons given for consulting their GPs included administrative matters, psychological support, reassurance, and advice, but also to a lesser extent, medical management. CONCLUSION: Patients' perspectives called attention to two aspects of the role of GPs in the French healthcare system: (a) the importance of GPs within an effective system for managing cancer patients, and (b) for some patients, GPs' relative lack of medical skill compared to oncologists. PMID- 26799831 TI - Ligularia fischeri extract attenuates liver damage induced by chronic alcohol intake. AB - Context Ligularia fischeri (Ledebour) Turcz. (Compositae) has been used as a leafy vegetable and in traditional medicine to treat hepatic disorder in East Asia. Objective The present study explores the antioxidant activity of LF aqueous extract on EtOH-induced oxidative stress accompanied by hepatotoxicity both in vitro and in vivo. Materials and methods In vitro study using the mouse liver NCTC-1469 cell line was conducted to estimate the cytotoxicity as well as the inhibitory effect of LF extract against alcohol-treated cell damage. In vivo study used an alcohol-fed Wister rat model orally administered EtOH (3.95 g/kg of body weight/d) with or without LF extract (100 or 200 mg/kg body weight) for 6 weeks. Serum and liver tissue were collected to evaluate hepatic injury and antioxidant-related enzyme activity. Results The EC50 value for the DPPH radical scavenging capacity of LF extract was 451.5 MUg/mL, whereas the IC50 value of LF extract in terms of EtOH-induced reactive oxygen species (ROS) generation was 98.3 MUg/mL without cell cytotoxicity. LF extract (200 mg/kg body weight) significantly reduced the triglyceride content of serum (33%) as well as hepatic lipid peroxidation (36%), whereas SOD activity was elevated three-fold. LF extract suppressed expression of CYP2E1 and TNF-alpha, and attenuated alcohol induced abnormal morphological changes. Discussion and conclusion LF extract attenuated liver damage induced by alcoholic oxidative stress through inhibition of ROS generation, down-regulation of CYP2E1, and activation of hepatic antioxidative enzymes. Homeostasis of the antioxidative defence system in the liver by LF extract mitigated hepatic disorder following chronic alcohol intake. PMID- 26799832 TI - Correction: Exploring the Support Needs of Family Caregivers of Patients with Brain Cancer Using the CSNAT: A Comparative Study with Other Cancer Groups. PMID- 26799834 TI - KS-Detect - Validation of Solar Thermal PCR for the Diagnosis of Kaposi's Sarcoma Using Pseudo-Biopsy Samples. AB - Resource-limited settings present unique engineering challenges for medical diagnostics. Diagnosis is often needed for those unable to reach central healthcare systems, making portability and independence from traditional energy infrastructure essential device parameters. In 2014, our group presented a microfluidic device that performed a solar-powered variant of the polymerase chain reaction, which we called solar thermal PCR. In this work, we expand on our previous effort by presenting an integrated, portable, solar thermal PCR system targeted towards the diagnosis of Kaposi's sarcoma. We call this system KS Detect, and we now report the system's performance as a diagnostic tool using pseudo-biopsy samples made from varying concentrations of human lymphoma cell lines positive for the KS herpesvirus (KSHV). KS-Detect achieved 83% sensitivity and 70% specificity at high (>= 10%) KSHV+ cell concentrations when diagnosing pseudo-biopsy samples by smartphone image. Using histology, we confirm that our prepared pseudo-biopsies contain similar KSHV+ cell concentrations as human biopsies positive for KS. Through our testing of samples derived from human cell lines, we validate KS-Detect as a viable, portable KS diagnostic tool, and we identify critical engineering considerations for future solar-thermal PCR devices. PMID- 26799835 TI - Longitudinal Effect of Surface Treatments Modified by NaOCl-Induced Deproteinization and Nd:YAG Laser on Dentin Permeability. AB - OBJECTIVE: The purpose of this study was to evaluate dentin permeability after dentin hypersensitivity treatments: fluoride, adhesive system, and collagen deproteinization with and without Nd:YAG laser exposure, and after erosive and abrasive challenges. MATERIALS AND METHODS: Dentin permeability was assessed by measuring dentinal fluid flow using a permeability device. Eighty bovine dentin specimens (6 mm diameter/1 mm thickness) had permeability measured in the presence of the smear layer and after removal of the smear layer by ethylenediaminetetraacetic acid (EDTA). They were then divided into eight groups according to treatment (n = 10): Group C, control; Group L, Nd:YAG laser; Group F, fluoride; Group FL, fluoride plus Nd:YAG laser; Group A, adhesive; Group AL, adhesive plus Nd:YAG laser; Group D, 10% NaOCl plus adhesive; and group DL, NaOCl plus adhesive plus Nd:YAG laser. Nd:YAG laser was irradiated at 60 mJ/pulse/10 Hz/47.7 J/cm2/1 W and applied freehanded without contact for 60 sec. Permeability was measured 24 h after the treatments. The specimens were exposed to erosive and abrasive challenges for 5 days. Erosive challenge was done by immersion in Coca Cola, four times a day/90 sec each. After the first and last erosive challenge of the day, the abrasive challenge was conducted by brushing the specimens (24,000 cycles/3.8 cm range/200 g weight), and permeability was measured again. Results were analyzed statistically using two factor ANOVA and Tukey tests (alpha = 0.05). RESULTS: With the exception of groups FL and A, all treatments reduced permeability. A significant reduction in permeability was seen when the treatments were combined with laser exposure. The association of adhesive and Nd:YAG laser led to the lowest rate of permeability after 24 h. NaOCl-induced deproteinization associated with Nd:YAG laser showed the lowest permeability rate after erosive/abrasive challenges. CONCLUSIONS: Dentin hypersensitivity treatments reduced dentin permeability when associated with Nd:YAG laser, even after erosive/abrasive challenges. PMID- 26799837 TI - Biomechanical Properties and Microstructural Analysis of the Human Nonaneurysmal Aorta as a Function of Age, Gender and Location: An Autopsy Study. AB - INTRODUCTION: The biomechanical failure properties and histological composition of the human nonaneurysmal aorta were studied. METHODS: Twenty-six human aortas were harvested from fresh cadavers at autopsy. A total of 153 circumferentially oriented strips were obtained from the aortas for biomechanical and histological studies. RESULTS: The failure load (6.18 +/- 2.03 vs. 4.85 +/- 2.04 N; p = 0.001), failure tension (19.88 +/- 9.05 vs. 14.53 +/- 7 N/cm; p = 0.001), failure strain (0.66 +/- 0.31 vs. 0.49 +/- 0.25; p = 0.003) and amount of elastic fibers (19.39 +/- 15.57 vs. 14.06 +/- 9.5%; p = 0.011) were all significantly higher for the thoracic than the abdominal aorta. There was a significant negative correlation between age and failure load (R = -0.35; p < 0.0001), failure stress (R = -0.63; p < 0.0001), failure tension (R = -0.52; p < 0.0001) and failure strain (R = -0.8; p < 0.0001). Male aortas had a higher failure load and failure tension than female aortas. CONCLUSION: The thoracic aorta has a higher strength and elasticity than the abdominal aorta. The elderly have weaker and stiffer aortas than the young. Male aortas are stronger than female aortas. PMID- 26799836 TI - Progressive Induction of Type 2 Diabetes: Effects of a Reality-Like Fructose Enriched Diet in Young Wistar Rats. AB - PURPOSE: The aim of this study was to characterize short and medium-lasting effects of fructose supplementation on young Wistar rats. The diet was similar to actual human consumption. METHODS: Three week old male rats were randomly divided into 2 groups: control (C; n = 16), fructose fed (FF; n = 16) with a fructose enriched drink for 6 or 12 weeks. Bodyweight, fasting glycemia and systolic blood pressure were monitored. Glucose tolerance was evaluated using an oral glucose tolerance test. Insulinemia was measured concomitantly and enable us to calculate insulin resistance markers (HOMA-IR, Insulin Sensitivity Index for glycemia: ISI gly). Blood chemistry analyses were performed. RESULTS: After six weeks of fructose supplementation, rats were not overweight but presented increased fasting glycemia, reduced glucose tolerance, and lower insulin sensitivity compared to control group. Systolic blood pressure and heart weight were also increased without any change in renal function (theoretical creatinine clearance). After twelve weeks of fructose supplementation, FF rats had increased bodyweight and presented insulin resistance (higher HOMA-IR, lower ISI-gly). Rats also presented higher heart volume and lower ASAT/ALAT ratio (presumed liver lesion). Surprisingly, the Total Cholesterol/Triglycerides ratio was increased only after six weeks of fructose supplementation, predicting a higher LDL presence and thus a higher risk of developing cardiovascular disease. This risk was no longer present after twelve weeks of a fructose enriched diet. CONCLUSION: On young Wistar rats, six weeks of fructose supplementation is sufficient to induce signs of metabolic syndrome. After twelve weeks of fructose enriched diet, rats are insulin resistant. This model enabled us to study longitudinally the early development of type 2 diabetes. PMID- 26799838 TI - Life Satisfaction and Morbidity among Postmenopausal Women. AB - OBJECTIVE: To investigate associations between morbidity and global life satisfaction in postmenopausal women taking into account type and number of diseases. MATERIALS AND METHODS: A total of 11,084 women (age range 57-66 years) from a population-based cohort of Finnish women (OSTPRE Study) responded to a postal enquiry in 1999. Life satisfaction was measured with a 4-item scale. Self reported diseases diagnosed by a physician and categorized according to ICD-10 main classes were used as a measure of morbidity. Enquiry data on health and lifestyle were used as covariates in the multivariate logistic models. RESULTS: Morbidity was strongly associated with life dissatisfaction. Every additional disease increased the risk of life dissatisfaction by 21.1% (p < .001). The risk of dissatisfaction was strongest among women with mental disorders (OR = 5.26; 95%CI 3.84-7.20) and neurological disorders (OR = 3.62; 95%CI 2.60-5.02) compared to the healthy (each p < .001). Smoking, physical inactivity and marital status were also associated with life dissatisfaction (each p < .001) but their introduction to the multivariate model did not attenuate the pattern of associations. CONCLUSIONS: Morbidity and life dissatisfaction have a disease specific and dose-dependent relationship. Even if women with mental and neurological disorders have the highest risk for life dissatisfaction, monitoring life satisfaction among aging women regardless of disorders should be undertaken in order to intervene the joint adverse effects of poor health and poor well being. PMID- 26799839 TI - Staphylococcus aureus Sortase A-Mediated Incorporation of Peptides: Effect of Peptide Modification on Incorporation. AB - The endogenous Staphylococcus aureus sortase A (SrtA) transpeptidase covalently anchors cell wall-anchored (CWA) proteins equipped with a specific recognition motif (LPXTG) into the peptidoglycan layer of the staphylococcal cell wall. Previous in situ experiments have shown that SrtA is also able to incorporate exogenous, fluorescently labelled, synthetic substrates equipped with the LPXTG motif (K(FITC)LPETG-amide) into the bacterial cell wall, albeit at high concentrations of 500 MUM to 1 mM. In the present study, we have evaluated the effect of substrate modification on the incorporation efficiency. This revealed that (i) by elongation of LPETG-amide with a sequence of positively charged amino acids, derived from the C-terminal domain of physiological SrtA substrates, the incorporation efficiency was increased by 20-fold at 10 MUM, 100 MUM and 250 MUM; (ii) Substituting aspartic acid (E) for methionine increased the incorporation of the resulting K(FITC)LPMTG-amide approximately three times at all concentrations tested; (iii) conjugation of the lipid II binding antibiotic vancomycin to K(FITC)LPMTG-amide resulted in the same incorporation levels as K(FITC)LPETG amide, but much more efficient at an impressive 500-fold lower substrate concentration. These newly developed synthetic substrates can potentially find broad applications in for example the in situ imaging of bacteria; the incorporation of antibody recruiting moieties; the targeted delivery and covalent incorporation of antimicrobial compounds into the bacterial cell wall. PMID- 26799841 TI - Comparing the Efficiency and Safety of Bipolar and Monopolar Transurethral Resection for Non-Muscle Invasive Bladder Tumors: A Systematic Review and Meta Analysis. AB - PURPOSE: To evaluate the efficacy and safety of bipolar and monopolar transurethral resection of bladder tumor (TURBT) procedures for non-muscle invasive bladder cancer (NMIBC) patients. MATERIALS AND METHODS: We searched for all studies investigating bipolar TURBT and monopolar TURBT for NMIBC patients in PubMed, Web of Knowledge, and the Cochrane Central Search Library. A systematic review and meta-analysis were performed. Efficacy was assessed by catheterization time, resection time, pathology, and recurrence rate. Safety was assessed by obturator nerve reflex, bladder perforation, hemoglobin decrease, and transfusion. RESULTS: Our searches identified eight studies. Bipolar TURBT is associated with decreased resection time, catheterization time, and hemoglobin changes. There were no statistically significant differences between bipolar TURBT and monopolar TURBT for rates of obturator nerve reflex, bladder perforation, and transfusion. The grade of cautery artifact had no different between the two procedures or even was lower in the bipolar arm. There was no significant difference in recurrence rate when comparing the two procedures. CONCLUSIONS: This systematic review indicates that the bipolar technique is more efficacious and safer for NMIBC patients. More large-scale, multicenter, randomized controlled studies are needed before final clinical recommendations can be made. PMID- 26799842 TI - New Perspectives on Drug Education/Prevention. AB - In 2014, Oregon, Alaska, and the District of Columbia joined Colorado and Washington as voters approved initiatives to legally regulate and tax marijuana for adults. Other states, including California, are likely to follow in 2016. While none of these new laws allow sales to minors, there is widespread concern about the potential impact of these reforms on teenagers. Many worry that legalization will "send the wrong message," and increase access and availability, leading to an escalation in teenage use. This new social, political and cultural context presents a new challenge, as marijuana gradually becomes a normal part of the adult world, akin to alcohol. The movement toward legalization provides an opportunity to re-think our approach to teen drug education/prevention. This is the moment to examine current approaches, and devise innovative, pragmatic strategies for dealing with teens and marijuana (and other drug use). As we examine the issue of drug education/prevention in the context of legalization, we detail efforts that have been tried, and what is realistically possible to accomplish, with the health and safety of teenagers our highest priority. A reality-based approach advocates honest, science-based information; encourages moderation, if experimentation persists; promotes an understanding of the legal consequences and social context of drug use; emphasizes safety through personal responsibility and knowledge; and encourages the delay of experimentation with all intoxicating substances until adulthood. PMID- 26799843 TI - A computational investigation on the substrate preference of ten-eleven translocation 2 (TET2). AB - TET proteins iteratively convert 5-methylcytosine (5mC) into 5 hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) in a Fe(ii)/alpha-ketoglutarate-dependent manner. Our previous biochemical studies revealed that TET proteins are more active on 5mC than on 5hmC and 5fC. However, the source of the substrate preference of TET proteins still remains largely elusive. Here, we investigated the substrate binding and catalytic mechanisms of oxidation reactions mediated by TET2 on different substrates through computational approaches. In accordance with previous experimental reports, our computational results suggest that TET2 can bind to different substrates with comparable binding affinities and the hydrogen abstraction step in the catalytic cycle acts as the rate-limiting step. Further structural characterization of the intermediate structures revealed that the 5-substitution groups on 5hmC and 5fC adopt an unfavorable orientation for hydrogen abstraction, which leads to a higher energy barrier for 5hmC and 5fC (compared to 5mC) and thus a lower catalytic efficiency. In summary, our mechanical insights demonstrate that substrate preference is the intrinsic property of TET proteins and our theoretical calculation results can guide further dry-lab or wet-lab studies on the catalytic mechanism of TET proteins as well as other Fe(ii)/alpha ketoglutarate (KG)-dependent dioxygenases. PMID- 26799840 TI - Treatment options for infections caused by carbapenem-resistant Enterobacteriaceae: can we apply "precision medicine" to antimicrobial chemotherapy? AB - INTRODUCTION: For the past three decades, carbapenems played a central role in our antibiotic armamentarium, trusted to effectively treat infections caused by drug-resistant bacteria. The utility of this class of antibiotics has been compromised by the emergence of resistance especially among Enterobacteriaceae. AREAS COVERED: We review the current mainstays of pharmacotherapy against infections caused by carbapenem-resistant Enterobacteriaceae (CRE) including tigecycline, aminoglycosides, and rediscovered 'old' antibiotics such as fosfomycin and polymyxins, and discuss their efficacy and potential toxicity. We also summarize the contemporary clinical experience treating CRE infections with antibiotic combination therapy. Finally, we discuss ceftazidime/avibactam and imipenem/relebactam, containing a new generation of beta-lactamase inhibitors, which may offer alternatives to treat CRE infections. We critically evaluate the published literature, identify relevant clinical trials and review documents submitted to the United States Food and Drug Administration. EXPERT OPINION: Defining the molecular mechanisms of resistance and applying insights about pharmacodynamic and pharmacokinetic properties of antibiotics, in order to maximize the impact of old and new therapeutic approaches should be the new paradigm in treating infections caused by CRE. A concerted effort is needed to carry out high-quality clinical trials that: i) establish the superiority of combination therapy vs. monotherapy; ii) confirm the role of novel beta lactam/beta-lactamase inhibitor combinations as therapy against KPC- and OXA-48 producing Enterobacteriaceae; and, iii) evaluate new antibiotics active against CRE as they are introduced into the clinic. PMID- 26799846 TI - For Fit's Sake: A Norms-Based Approach to Healthy Behaviors Through Influence of Presumed Media Influence. AB - Based on the influence of presumed media influence (IPMI) model as the theoretical framework, this study examines how injunctive norms and personal norms mediate the influence of healthy lifestyle media messages on public intentions to engage in two types of healthy lifestyle behaviors-physical activity and healthy diet. Nationally representative data collected from 1,055 adults in Singapore demonstrate partial support for the key hypotheses that make up the extended IPMI model, highlighting the importance of a norms-based approach in health communication. Our results indicate that perceived media influence on others indirectly shaped public intentions to engage in healthy lifestyle behaviors through personal norms and attitude, providing partial theoretical support for the extended IPMI model. Practical implications for health communicators in designing health campaigns media messages to motivate the public to engage in healthy lifestyle are discussed. PMID- 26799847 TI - A mechanistic review on plant-derived natural compounds as dietary supplements for prevention of inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) is a recurrent idiopathic inflammatory condition, characterized by disruption of the gut mucosal barrier. This mechanistic review aims to highlight the significance of plant-derived natural compounds as dietary supplements, which can be used in addition to restricted conventional options for the prevention of IBD and induction of remission. Various clinical trials confirmed the effectiveness and tolerability of natural supplements in patients with IBD. Mounting evidence suggests that these natural compounds perform their protective and therapeutic effect on IBD through numerous molecular mechanisms, including anti-inflammatory and immunoregulatory, anti oxidative stress, modulation of intracellular signaling transduction pathways, as well as improving gut microbiota. In conclusion, natural products can be considered as dietary supplements with therapeutic potential for IBD, provided that their safety and efficacy is confirmed in future well-designed clinical trials with adequate sample size. PMID- 26799850 TI - Extinction of fear is facilitated by social presence: Synergism with prefrontal oxytocin. AB - This study addressed the question of whether extinction in pairs would have a beneficial effect on extinction of fear conditioning. To that end, we established an experimental setting for extinction in which we trained animals to extinguish contextual fear memory in pairs. Taking advantage of the role of oxytocin (OT) in the medial prefrontal cortex (mPFC) in the mediation of memory extinction and social interaction, we also sought to study its role in social interaction induced effects on extinction. Our results clearly show that the social presence of another animal in the extinction context facilitates extinction, and that this facilitation is mediated through mPFC-OT. Our results suggest that social interaction may be a positive regulator of fear inhibition, implying that social interaction may be an easy, accessible therapeutic tool for the treatment of fear associated disorders. PMID- 26799849 TI - Psychosocial determinants of diurnal alpha-amylase among healthy Quebec workers. AB - Salivary alpha-amylase (sAA) is a stress-sensitive biomarker the shows promise as an indirect proxy of sympathetic-adrenal-medullary axis activities that are otherwise difficult to discern non-invasively. This comprehensive study investigated diurnal sAA in association with numerous psychosocial characteristics related to mental health, work stress, and non-work stress. Participants included 395 workers (56.1% women, age: M=41.3, SD=10.81) from across 34 distinct workplaces. Diurnal sAA was sampled over two non-consecutive work days at awakening, 30 min after awakening, 14h00, 16h00, and bedtime. Well validated psychometrics and survey items were used to measure mental health (psychological distress, depression, burnout, work characteristics) (task design, demands, social relations, gratifications), and non-work characteristics (marital/parental status, economic statuses, marital and parental stress, work family conflicts). Preliminary results revealed that men showed occasionally higher sAA concentrations than women. Multilevel regressions were used to analyze sAA concentrations nested according to levels (i) for each time-point, (ii) between workers, and (iii) across workplaces while covarying for time of awakening, sex, age, cigarette smoking, alcohol consumption, regular physical activity, psychotropic drug use, and body mass index. Main results revealed that psychological demands, support from colleagues, interpersonal conflicts, job recognition and job insecurity appear to be associated with diurnal sAA, while non-work factors did not. Our findings showing a distinct diurnal profile for sAA replicate and expand those of Nater et al. (2007, Psychoneuroendocrinology 32, 392-401), providing further evidence that sAA is associated to subjective psychosocial factors. PMID- 26799853 TI - Telomeropathies: an emerging spectrum of disorder with important implications for patients with interstitial lung disease. AB - Growing evidence demonstrates that a number of clinical disorders may be related to genetic defects in telomeres replication and extensions. Overall, these syndromes are referred to as telomeropathies or telomeres disorders or syndromes; they are increasingly being identified. In adulthood, idiopathic pulmonary fibrosis (IPF) is the most common symptom of telomeropathy. IPF is a progressive and fatal disease characterized by scarring of the lungs that thickens the interstitium ultimately leading to irreversible respiratory failure. Starting from this basis, the present review analyzes and discusses the findings of a relevant paper by Gautam George and colleagues from the Division of Pulmonary and Critical Care Medicine at Brigham and Women's Hospital and Harvard Medical School in Boston (USA) recently appeared on the prestigious journal CHEST. In a cohort of patients addressed to lung transplantation, authors were able to demonstrate that subclinical bone marrow and liver abnormalities can be seen in patients with interstitial lung disease (ILD) and short telomeres, in some cases in the absence of clinically significant abnormalities in peripheral blood count and liver function tests. This observation sustains the rationale for further studies aimed to validate telomere length testing as a useful parameter as part of the evaluation for transplant candidacy. A deeper clarification of the complex link between IPF and short telomeres and telomeropathies is required for a new ILD classification, aimed to a fullpersonalized approach to the disease. PMID- 26799851 TI - Stress-induced neuroinflammatory priming is time of day dependent. AB - Circadian rhythms are endogenous cycles of physiology and behavior that align with the daily rotation of the planet and resulting light-dark cycle. The circadian system ensures homeostatic balance and regulates many aspects of physiology, including the stress response and susceptibility to and/or severity of stress-related sequelae. Both acute and chronic stressors amplify neuroinflammatory responses to a subsequent immune challenge, however it is not known whether circadian timing of the stressor regulates the priming response. Here, we test whether stress-induced neuroinflammatory priming is regulated by the circadian system. As has been previously shown, exposure to 100 inescapable tails shocks (IS) increased hippocampal cytokines following a subsequent inflammatory challenge. However, this effect was limited to animals that experienced the stressor during the light phase. Rats exposed to stress during the dark phase did not alter inflammatory potential following lipopolysaccharide (LPS) challenge. To determine whether microglia might be involved in diurnal differences in neuroinflammatory priming, microglia were isolated 24h after stress that occurred either during the middle of the light or dark phase. Only microglia isolated from animals stressed during the light phase demonstrated an exaggerated inflammatory response when treated ex vivo with LPS. To determine possible circadian dependency of microglia responsiveness to glucocorticoids - the likely proximal mediator for stress associated neuroinflammatory priming - microglia were isolated during the middle of the light or dark phase and treated ex vivo with corticosterone. Glucocorticoids treatment downregulated CX3CR1 and CD200R, two genes involved in microglial inflammatory "off" signaling; however, there was no effect of time of day on expression of either gene. Importantly, while absolute concentrations of corticosterone were comparable following IS during the light and dark phase, the magnitude of change in corticosterone was greater during the light phase. This work highlights the importance of studying circadian rhythms to elucidate biological mechanisms of stress. PMID- 26799852 TI - Evidence of a unique and common genetic etiology between the CAR and the remaining part of the diurnal cycle: A study of 14 year-old twins. AB - INTRODUCTION: By and large, studies have reported moderate contributions of genetic factors to cortisol secreted in the early morning and even smaller estimates later in the day. In contrast, the cortisol awakening response (CAR) has shown much stronger heritability estimates, which prompted the hypothesis that the etiology of cortisol secretion may vary according to the time of day. A direct test of this possibility has, however, not yet been performed. OBJECTIVE: To describe the specific and common etiology of the CAR, awakening level and cortisol change from morning to evening in an age-homogenous sample of twin adolescents. METHODS: A total of 592 participants of the Quebec Newborn Twin Study, a population-based 1995-1998 cohort of families with twins in Canada, have collected saliva at awakening, 30 min later, at the end of afternoon and in the evening over four collection days. RESULTS: Multivariate Cholesky models showed both specific and common sources of variance between the CAR, awakening and cortisol diurnal change. The CAR had the strongest heritability estimates, which, for the most part, did not overlap with the other indicators. Conversely, similar magnitudes of genetic and environmental contributions were detected at awakening and for diurnal change, which partially overlapped. CONCLUSION: Our study unraveled differences between the latent etiologies of the CAR and the rest of the diurnal cycle, which may contribute to identify regulatory genes and environments and detangle how these indicators each relate to physical and mental health. PMID- 26799855 TI - The clinical risk factors associated with postoperative bile leakage after hepatectomy: a meta-analysis. AB - INTRODUCTION: The occurrence of bile leakage (BL) is one of the major contributors to the morbidity after hepatectomy. However, the clinical risk factors associated with postoperative BL remains controversial. This study aims to further assess the risk factors for BL. EVIDENCE ACQUISITION: We comprehensively searched the electronic databases of PubMed, EMBASE, Web of Science and the Cochrane Library for studies published before October 10th, 2015. Cohort studies, case-control studies, and randomized controlled trials that examined clinical risk factors for BL were included. EVIDENCE SYNTHESIS: Eighteen retrospective studies including a total of 9270 patients were identified. From the pooled analysis, twelve factors were found to be significantly associated to the increased rate of BL, including previous liver or biliary surgery, anatomic resection, major hepatectomy, right anterior sectionectomy, left trisectionectomy, central bisectionectomy, blood transfusion, operative time, bile duct reconstruction, segment 1 involved, segment 2 involved, segment 5 involved. By contrast, hepatic fibrosis/cirrhosis, left lateral sectionectomy were found to be correlated to decreased incidence of BL. CONCLUSIONS: Our meta analysis reveals that previous liver or biliary surgery, anatomic resection, major hepatectomy, right anterior sectionectomy, left trisectionectomy, central bisectionectomy, blood transfusion, operative time, bile duct reconstruction, resection of segments 1, 2 and 5 involved had significant positive correlation with increased risk of BL, on the contrary, hepatic fibrosis/cirrhosis, left lateral sectionectomy had the opposite effect. PMID- 26799857 TI - Multi-Functional Surface Engineering for Li-Excess Layered Cathode Material Targeting Excellent Electrochemical and Thermal Safety Properties. AB - The Li(Li(0.18)Ni(0.15)Co(0.15)Mn(0.52))O2 cathode material is modified by a Li4M5O12-like heterostructure and a BiOF surface layer. The interfacial heterostructure triggers the layered-to-Li4M5O12 transformation of the material which is different from the layered-to-LiMn2O4 transformation of the pristine Li(Li(0.18)Ni(0.15)Co(0.15)Mn(0.52))O2. This Li4M5O12-like transformation helps the material to keep high working voltage, long cycle life and excellent rate capability. Mass spectrometry, in situ X-ray diffraction and transmission electron microscope show that the Li4M5O12-like phase prohibits oxygen release from the material bulk at elevated temperatures. In addition, the BiOF coating layer protects the material from harmful side reactions with the electrolyte. These advantages significantly improve the electrochemical performance of Li(Li(0.18)Ni(0.15)Co(0.15)Mn(0.52))O2. The material shows a discharge capacity of 292 mAh g(-1) at 0.2 C with capacity retention of 92% after 100 cycles. Moreover, a high discharge capacity of 78 mAh g(-1) could be obtained at 25 C. The exothermic temperature of the fully charged electrode is elevated from 203 to 261 degrees C with 50% reduction of the total thermal release, highlighting excellent thermal safety of the material. PMID- 26799856 TI - Prognostic value of matrix metalloproteinase 9 in nasopharyngeal carcinoma: a meta-analysis. AB - INTRODUCTION: Recent studies have shown that matrix metalloproteinase 9 (MMP9) plays a vital role in tumor metastasis and is overexpressed in many human cancers. However, the prognostic value of MMP9 overexpression in nasopharyngeal carcinoma (NPC) is conflicting and heterogeneous. We therefore conducted a meta analysis to investigate the association between MMP9 expression and the prognostic value in NPC. EVIDENCE ACQUISITION: Relevant literature that evaluating the relationship between MMP-9 expression and the outcome of NPC patients were searched in PubMed, Embase, Cochrane, Ovid Medline and Chinese wanfang databases updated to May 2015. The primary study outcome was overall survival (OS). Secondary endpoint was disease-free survival (DFS). The combined hazard ratios (HRs) with their 95% confidence intervals (CIs) were assessed using STATA 12.0 software. EVIDENCE SYNTHESIS: A total of 6 studies were included with the defined including and excluding criteria and subjected to meta-analysis. The pooled result showed that MMP9 overexpression was significantly associated with poor prognosis in terms of OS (HR: 1.65, 95% CI: 1.38-1.95, P<0.0001) and poor DFS (HR: 1.61, 95% CI: 1.28-2.02, P<0.0001) in NPC patients. Subgroup analysis suggested that high expression of MMP9 was associated with poor OS in NPC patients with different sample types. No evidence for publication bias was observed in our meta-analysis. CONCLUSIONS: The current limited evidence suggests that increased MMP9 expression is associated with poor OS, and DFS in NPC. Therefore, we conclude that overexpression of MMP9 in both NPC tissue and blood sample might serve as an indicator of prognosis in NPC patients. PMID- 26799858 TI - Validation of CE modeling with a contactless conductivity array detector. AB - Dynamic computer simulation data are compared for the first time with CE data obtained with a laboratory made system comprising an array of 8 contactless conductivity detectors (C(4) Ds). The experimental setup featured a 50 MUm id linear polyacrylamide (LPA) coated fused-silica capillary of 70 cm length and a purpose built sequential injection analysis manifold for fluid handling of continuous or discontinuous buffer configurations and sample injection. The LPA coated capillary exhibits a low EOF and the manifold allows the placement of the first detector at about 2.7 cm from the sample inlet. Agreement of simulated electropherograms with experimental data was obtained for the migration and separation of cationic and anionic analyte and system zones in CZE configurations in which EOF and other column properties are constant. For configurations with discontinuous buffer systems, including ITP, experimental data obtained with the array detector revealed that the EOF is not constant. Comparison of simulation and experimental data of ITP systems provided the insight that the EOF can be estimated with an ionic strength dependent model similar to that previously used to describe EOF in fused-silica capillaries dynamically double coated with Polybrene and poly(vinylsulfonate). For the LPA coated capillaries, the electroosmotic mobility was determined to be 17-fold smaller compared to the case with the charged double coating. Simulation and array detection provide means for quickly investigating electrophoretic transport and separation properties. Without realistic input parameters, modeling alone is not providing data that match CE results. PMID- 26799861 TI - In Situ Observation on Dislocation-Controlled Sublimation of Mg Nanoparticles. AB - Sublimation is an important endothermic phase transition in which the atoms break away from their neighbors in the crystal lattice and are removed into the gas phase. Such debonding process may be significantly influenced by dislocations, the crystal defect that changes the bonding environment of local atoms. By performing systematic defects characterization and in situ transmission electron microscopy (TEM) tests on a core--shell MgO-Mg system, which enables us to "modulate" the internal dislocation density, we investigated the role of dislocations on materials' sublimation with particular focus on the sublimation kinetics and mechanism. It was observed that the sublimation rate increases significantly with dislocation density. As the density of screw dislocations is high, the intersection of screw dislocation spirals creates a large number of monatomic ledges, resulting in a "liquid-like" motion of solid-gas interface, which significantly deviates from the theoretically predicted sublimation plane. Our calculation based on density functional theory demonstrated that the remarkable change of sublimation rate with dislocation density is due to the dramatic reduction in binding energy of the monatomic ledges. This study provides direct observation to improve our understanding on this fundamental phase transition as well as to shed light on tuning materials' sublimation by "engineering" dislocation density in applications. PMID- 26799862 TI - Provision of Meaningful Care at Diagnosis, Birth, and after Stillbirth: A Qualitative Synthesis of Parents' Experiences. AB - BACKGROUND: The care provided to parents experiencing stillbirth can have significant and lasting impacts on their immediate and long-term psychological well being. The aim of this qualitative synthesis was to investigate parents' experiences of care received during and after stillbirth. METHODS: Qualitative findings extracted from 20 included studies were pooled using a meta-aggregative approach. RESULTS: Four meta-syntheses encompassing parents' experiences of care at diagnosis of stillbirth, induction and birth, immediately postbirth and onwards, revealed care strategies that parents appreciated and found helpful, and also actions and behaviors that were distressing. Helpful strategies included a warm and sensitive communication style, provision of clear and understandable information, shared decision making, and respect for individual needs and preferences. Parents appreciated guidance from health care professionals about seeing and holding, including being prepared for their baby's possible appearance, information on how to spend time with their baby, and collection of memorabilia. After stillbirth, offers of follow-up care, including referrals for professional support, were appreciated. CONCLUSIONS: Care received during and after stillbirth may have lasting impacts on parents' future well being. Health care professionals may aid in improving parents' well being after stillbirth by providing care that is cognizant of parents' emotional states. Care strategies arising from the findings of this review are suggested. PMID- 26799859 TI - Evaluation of cell-laden polyelectrolyte hydrogels incorporating poly(L-Lysine) for applications in cartilage tissue engineering. AB - To address the lack of reliable long-term solutions for cartilage injuries, strategies in tissue engineering are beginning to leverage developmental processes to spur tissue regeneration. This study focuses on the use of poly(L lysine) (PLL), previously shown to up-regulate mesenchymal condensation during developmental skeletogenesis in vitro, as an early chondrogenic stimulant of mesenchymal stem cells (MSCs). We characterized the effect of PLL incorporation on the swelling and degradation of oligo(poly(ethylene) glycol) fumarate) (OPF) based hydrogels as functions of PLL molecular weight and dosage. Furthermore, we investigated the effect of PLL incorporation on the chondrogenic gene expression of hydrogel-encapsulated MSCs. The incorporation of PLL resulted in early enhancements of type II collagen and aggrecan gene expression and type II/type I collagen expression ratios when compared to blank controls. The presentation of PLL to MSCs encapsulated in OPF hydrogels also enhanced N-cadherin gene expression under certain culture conditions, suggesting that PLL may induce the expression of condensation markers in synthetic hydrogel systems. In summary, PLL can function as an inductive factor that primes the cellular microenvironment for early chondrogenic gene expression but may require additional biochemical factors for the generation of fully functional chondrocytes. PMID- 26799863 TI - Sex differences and gender-invariance of mother-reported childhood problem behavior. AB - Prevalence and severity of childhood behavioral problems differ between boys and girls, and in psychiatry, testing for gender differences is common practice. Population-based studies show that many psychopathology scales are (partially) Measurement Invariance (MI) with respect to gender, i.e. are unbiased. It is, however, unclear whether these studies generalize towards clinical samples. In a psychiatric outpatient sample, we tested whether the Child Behavior Checklist 6 18 (CBCL) is unbiased with respect to gender. We compared mean scores across gender of all syndrome scales of the CBCL in 3271 patients (63.3% boys) aged 6 18. Second, we tested for MI on both the syndrome scale and the item-level using a stepwise modeling procedure. Six of the eight CBCL syndrome scales included one or more gender-biased items (12.6% of all items), resulting in slight over- or under-estimation of the absolute gender difference in mean scores. Two scales, Somatic Complaints and Rule-breaking Behavior, contained no biased items. The CBCL is a valid instrument to measure gender differences in problem behavior in children and adolescents from a clinical sample; while various gender-biased items were identified, the resulting bias was generally clinically irrelevant, and sufficient items per subscale remained after exclusion of biased items. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26799864 TI - Peptide retention time prediction. AB - Most methods for interpreting data from shotgun proteomics experiments are to large degree dependent on being able to predict properties of peptide-ions. Often such predicted properties are limited to molecular mass and fragment spectra, but here we put focus on a perhaps underutilized property, a peptide's chromatographic retention time. We review a couple of different principles of retention time prediction,and their applications within computational proteomics. (c) 2016 Wiley Periodicals, Inc. Mass Spec Rev 36:615-623, 2017. PMID- 26799867 TI - Section I. Editorial. PMID- 26799865 TI - Social inclusion and the Fatosphere: the role of an online weblogging community in fostering social inclusion. AB - Overweight and obesity are one of the most salient issues within society today, and the stigmatisation of overweight individuals is prevalent and widespread. Utilising interviews with 44 individuals who blog within an online fat acceptance community known as the Fatosphere, participants' perceptions of inclusion and exclusion were examined within their offline and online environments. Additionally, the effect this had on their offline lives was examined. Participants described a profound sense of exclusion within their offline lives through three agencies: the medicalisation of 'fatness', the weight loss industry and the media, which echoed descriptions of moral judgement. Furthermore, a sense of inclusion was described within the Fatosphere through the protection and support that they found within this 'safe space'. The effects of the Fatosphere influenced their lives in both negative and positive ways, allowing them to better deal with stigma and discrimination, but sometimes effecting their offline relationships in a negative manner. The Fatosphere provides a unique opportunity for corpulent individuals to engage in a community that is removed from the prominent weight-related discourse within modern society. PMID- 26799869 TI - Section II. Critical Reviews. PMID- 26799868 TI - The New Dawn of Virtual Reality in Health Care: Medical Simulation and Experiential Interface. AB - The 90s and 00s saw great hopes that virtual reality was poised to sweep health care and change everything. But it didn't. Though researchers could immerse themselves in more complex virtual environments, the chasm between that digital experience and the complexity of real life - using a VR system in an hospital without a dedicated technician was a real challenge - just was too great. Now the situation is changing quickly. The rise of Oculus Rift and the shift of virtual reality from PC to mobile phones thanks to both the Oculus designed Gear VR headsets for Samsung phones and the Google Cardboard project are going to transform health care tools and experiences. PMID- 26799870 TI - Defining Cyberbullying: A Multiple Perspectives Approach. AB - To date, there has been a lack of consensus among researchers, practitioners, and laypersons about the definition of cyberbullying. Researchers have typically applied the key characteristics of intent to harm, power imbalance, and repetition from the definition of traditional bullying to cyberbullying, but how these characteristics transfer from the real world to a technology-mediated environment remains ambiguous. Moreover, very few studies have specifically investigated how cyberbullying is defined from the perspective of bullies, victims and bystanders. To this end, this article will propose a three-part definition of cyberbullying, which incorporates the perspective of bullies, victims and bystanders. PMID- 26799871 TI - Explaining Work Exhaustion From a Coping Theory Perspective: Roles of Techno Stressors and Technology-Specific Coping Strategies. AB - The purpose of this study is to theoretically develop and empirically examine a general coping theory model which explicates the indirect effects of key job related techno-stressors on job exhaustion. Through this study, we show that techno-stress creators are detrimental to employee well-being and should be treated accordingly. Specifically, we first argue that key techno-stress creators on the job, namely techno-invasion and techno-overload, drive unpleasant states such as work-family conflict and distress. Next, we rely on general coping theory and argue that people respond to these states differently, but with both adaptive and maladaptive technology-specific coping strategies. Adaptive coping behaviors are argued to ultimately reduce work exhaustion, and maladaptive coping strategies are argued to increase it. The proposed model was tested and validated with structural equation modeling techniques applied to self-reported data obtained from a sample of 242 employees of a large organization in the United States. Implications for theory and practice are discussed. PMID- 26799872 TI - Section III. Evaluation Studies. PMID- 26799873 TI - If You Build It, They Will Come, But What Will Wounded Warriors Experience? Presence in the CAREN. AB - Military service members (SMs) are surviving complex battlefield injuries at higher rates than ever before. Cutting-edge technologies are increasingly being employed to improve assessment and treatment of these complex injuries. The Computer Assisted Rehabilitation Environment (CAREN) is a comprehensive immersive environment, featuring a treadmill, curved panoramic screen, audio array, and infrared cameras to capture movement. While the CAREN has been progressively incorporated in treatment and research, little has been reported regarding participants' subjective experiences, particularly in relation to the signature wounds of the Iraq and Afghanistan wars, traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). Here we report participant presence, in a cohort of SMs with complex, frequently dual-diagnosis injuries (N=148; 95% TBI; 58% PTSD) engaging in CAREN-driven treatment. Using a presence questionnaire, participants rated aspects of the CAREN on a 7-point Likert scale and a presence score was calculated. The average presence score was 46.83 (SD=6.04; possible score range 7-63), with 95% of participants reporting scores >36. Those with motion sickness and eye discomfort reported lower presence, whereas those with PTSD reported higher presence. Presence did not vary according to TBI severity. Overall, SMs with complex injuries experience presence in the CAREN. However, presence may be adversely affected by CAREN-associated symptoms such as motion sickness. PMID- 26799874 TI - Evaluating User Experience of Augmented Reality Eyeglasses. AB - Augmented reality based applications have been experimented with in various contexts. Typically, the interaction is supported by handled devices, which, in specific scenarios, may hinder the interaction and spoil the experience of use, as the user is forced to hold the device and to keep her eyes on it at all times. The recent launch on the market of light-weight, unobtrusive head-mounted displays may change this circumstance. Nevertheless, investigations are needed to understand if such head-worn devices effectively outperform handheld devices in terms of comfort and pleasant experience of use. Here we present two experiments aimed at assessing the comfort of wearing a head-worn, see-through AR viewer in both a controlled and a natural setting. Besides the comfort of wearing the device, aspects related to the user experience were also investigated in the field evaluation. Our findings suggest that the head-mounted display examined is comfortable to wear regardless of the context of use. Interestingly in the field trails, participants did not express concern for the impression they would have made on other people and the experience of use was overall pleasant. Possible issues related to visual fatigue emerged. PMID- 26799875 TI - Bridging Minds: A Mixed Methodology to Assess Networked Flow. AB - The main goal of this contribution is to present a methodological framework to study Networked Flow, a bio-psycho-social theory of collective creativity applying it on creative processes occurring via a computer network. First, we draw on the definition of Networked Flow to identify the key methodological requirements of this model. Next, we present the rationale of a mixed methodology, which aims at combining qualitative, quantitative and structural analysis of group dynamics to obtain a rich longitudinal dataset. We argue that this integrated strategy holds potential for describing the complex dynamics of creative collaboration, by linking the experiential features of collaborative experience (flow, social presence), with the structural features of collaboration dynamics (network indexes) and the collaboration outcome (the creative product). Finally, we report on our experience with using this methodology in blended collaboration settings (including both face-to-face and virtual meetings), to identify open issues and provide future research directions. PMID- 26799876 TI - Teaching-learning: stereoscopic 3D versus Traditional methods in Mexico City. AB - In the UNAM Faculty of Odontology, we use a stereoscopic 3D teaching method that has grown more common in the last year, which makes it important to know whether students can learn better with this strategy. The objective of the study is to know, if the 4th year students of the bachelor's degree in dentistry learn more effectively with the use of stereoscopic 3D than the traditional method in Orthodontics. METHODS: first, we selected the course topics, to be used for both methods; the traditional method using projection of slides and for the stereoscopic third dimension, with the use of videos in digital stereo projection (seen through "passive" polarized 3D glasses). The main topic was supernumerary teeth, including and diverted from their guide eruption. Afterwards we performed an exam on students, containing 24 items, validated by expert judgment in Orthodontics teaching. The results of the data were compared between the two educational methods for determined effectiveness using the model before and after measurement with the statistical package SPSS 20 version. The results presented for the 9 groups of undergraduates in dentistry, were collected with a total of 218 students for 3D and traditional methods, we found in a traditional method a mean 4.91, SD 1.4752 in the pretest and X=6.96, SD 1.26622, St Error 0.12318 for the posttest. The 3D method had a mean 5.21, SD 1.996779 St Error 0.193036 for the pretest X= 7.82, SD =0.963963, St Error 0.09319 posttest; the analysis of Variance between groups F= 5.60 Prob > 0.0000 and Bartlett's test for equal variances 21.0640 Prob > chi2 = 0.007. These results show that the student's learning in 3D means a significant improvement as compared to the traditional teaching method and having a strong association between the two methods. CONCLUSION: The findings suggest that the stereoscopic 3D method lead to improved student learning compared to traditional teaching. PMID- 26799877 TI - The Effect Of 3D Audio And Other Audio Techniques On Virtual Reality Experience. AB - Three studies were conducted to examine the effect of audio on people's experience in a virtual world. The first study showed that people could distinguish between mono, stereo, Dolby surround and 3D audio of a wasp. The second study found significant effects for audio techniques on people's self reported anxiety, presence, and spatial perception. The third study found that adding sound to a visual virtual world had a significant effect on people's experience (including heart rate), while it found no difference in experience between stereo and 3D audio. PMID- 26799878 TI - The Role of Expectations in Game-Based Training. AB - The present work seeks to examine the importance of expectancies in computer mediated treatment and training programs. Two studies examining the role of patient and trainee expectations are presented. Study 1 investigated how expectations of a training game for military surgical teams influence training performance outcomes. The findings have implications for the administration of game-based treatment and training systems. Study 2 explored how pre-treatment expectancies influence post-treatment reactions to a game-based intervention for post-traumatic stress disorder (PTSD). Results indicate that self-efficacy plays a mediating role in the relationship between expectancies and reactions. Together, these studies offer implications regarding the critical role of attitudes towards game-based training and treatment mechanisms. PMID- 26799879 TI - Decision Making and Cognitive Behavioral Flexibility in a OCD Sample: a Study in a Virtual Environment. AB - Neuropsychological disorders are common in Obsessive-Compulsive Disorder (OCD) patients. Executive functions, verbal fluency and verbal memory, shifting attention from one aspect of stimuli to others, mental flexibility, engaging in executive planning and decision making, are the most involved cognitive domains. We focus on two aspects of neuropsychological function: decision making and cognitive behavioral flexibility, assessed through a virtual version of the Multiple Errand Test (V-MET), developed using the NeuroVR software. Thirty OCD patients were compared with thirty matched control subjects. The results showed the presence of difficulties in OCD patients with tasks where the goal is not clear, the information is incomplete or the parameters are ill-defined. PMID- 26799880 TI - Measuring Co-Presence and Social Presence in Virtual Environments - Psychometric Construction of a German Scale for a Fear of Public Speaking Scenario. AB - Virtual reality exposure therapy (VRET) applications use high levels of fidelity in order to produce high levels of presence and thereby elicit an emotional response for the user (like fear for phobia treatment). State of research shows mixed results for the correlation between anxiety and presence in virtual reality exposure, with differing results depending on specific anxiety disorders. A positive correlation for anxiety and presence for social anxiety disorder is not proven up to now. One reason might be that plausibility of the simulation, namely including key triggers for social anxiety (for example verbal and non-verbal behavior of virtual agents that reflects potentially negative human evaluation) might not be acknowledged in current presence questionnaires. A German scale for measuring co-presence and social presence for virtual reality (VR) fear of public speaking scenarios was developed based on a translation and adaption of existing co-presence and social presence questionnaires. A sample of N = 151 students rated co-presence and social presence after using a fear of public speaking application. Four correlated factors were derived by item- and principle axis factor analysis (Promax rotation), representing the presenter's reaction to virtual agents, the reactions of the virtual agents as perceived by the presenter, impression of interaction possibilities, and (co-)presence of other people in the virtual environment. The scale developed can be used as a starting point for future research and test construction for VR applications with a social context. PMID- 26799881 TI - Being Present In Space: The Role Of Allocentric And Egocentric Reference Frames. AB - The general aim of the present study was to investigate the effect of an interactive aerial view of the experienced environment during the encoding and retrieving of spatial information on the feeling of presence. Our findings showed that this real-time interactive aerial view (both small and large) during the encoding and retrieval of spatial information seems to led to a greater sense of presence. It is argued that the use of this aerial view, which provides a real time allocentric viewpoint-dependent spatial representation, would ease the translation of a stored allocentric representation into an egocentric one, and this process, consequently, would help individuals to feel present in space. PMID- 26799882 TI - Combining Face-to-face Therapy with Computerized Techniques: A therapists' Attitudes Survey. AB - Therapists' attitudes towards the use of computerized therapies have been the focus of numerous studies. Nevertheless, little is known about therapists' perception of a combined model that uses computerized methods as adjuncts to face to-face (FTF) therapy. Current study surveyed 87 Israeli therapists' attitudes towards such combined model. Results show that more than half of therapists find it as potentially more effective than regular therapy, better for providing feedback and maintaining continuity of care. More than a third of the therapists found it may elicit better patient satisfaction and engagement. With respect to different modalities, therapists indicated that e-mail correspondence are better suited for combining with FTF treatments. Theoretical orientation had little effect on practitioners' attitudes. Finally, more than half of the therapists showed willingness to undergo training for a combined model. Compared to previously researched computerized interventions, current study indicates more positive attitudes and acceptability among therapists towards an integrative model. PMID- 26799883 TI - Virtual Reality to Train Diagnostic Skills in Eating Disorders. Comparison of two Low Cost Systems. AB - Enhancing the ability to perform differential diagnosis and psychopathological exploration is important for students who wish to work in the clinical field, as well as for professionals already working in this area. Virtual reality (VR) simulations can immerse students totally in educational experiences in a way that is not possible using other methods. Learning in a VR environment can also be more effective and motivating than usual classroom practices. Traditionally, immersion has been considered central to the quality of a VR system; immersive VR is considered a special and unique experience that cannot achieved by three dimensional (3D) interactions on desktop PCs. However, some authors have suggested that if the content design is emotionally engaging, immersive systems are not always necessary. The main purpose of this study is to compare the efficacy and usability of two low-cost VR systems, offering different levels of immersion, in order to develop the ability to perform diagnostic interviews in eating disorders by means of simulations of psychopathological explorations. PMID- 26799885 TI - Section IV. Original Research. PMID- 26799884 TI - How To Protect Children From Internet Predators: A Phenomenological Study. AB - Teenage Internet users are the fastest growing segment in the Internet user population. These teenagers are at risk of sexual assault from Internet predators. This phenomenological study explored teacher and counselors' perceptions of how to prevent this sexual assault. Twenty-five teacher and counselor participants were interviewed. A modified van Kaam method was used to analyze the data and develop themes. Participants stated that mainly the lack of parental support and social networking website were the circumstances leading to teenage Internet sexual assault, while teen needs and gratification usually played a role in teen encounters with predators on the Internet. There were 5 emergent themes in this phenomenological study and those themes were; lack of parental support, social networking websites and chat rooms, teenage need for relationships, instant gratification among teenagers, improved parental support. PMID- 26799886 TI - The Identity Mapping Project: Demographic differences in patterns of distributed identity. AB - The advent of cloud computing and a multi-platform digital environment is giving rise to a new phase of human identity called "The Distributed Self." In this conception, aspects of the self are distributed into a variety of 2D and 3D digital personas with the capacity to reflect any number of combinations of now malleable personality traits. In this way, the source of human identity remains internal and embodied, but the expression or enactment of the self becomes increasingly external, disembodied, and distributed on demand. The Identity Mapping Project (IMP) is an interdisciplinary collaboration between psychology and computer Science designed to empirically investigate the development of distributed forms of identity. Methodologically, it collects a large database of "identity maps" - computerized graphical representations of how active someone is online and how their identity is expressed and distributed across 7 core digital domains: email, blogs/personal websites, social networks, online forums, online dating sites, character based digital games, and virtual worlds. The current paper reports on gender and age differences in online identity based on an initial database of distributed identity profiles. PMID- 26799887 TI - Using A Facebook Group As An Adjunct To A Pilot mHealth Physical Activity Intervention: A Mixed Methods Approach. AB - In the United States, most adolescents do not obtain the recommended amounts of physical activity for optimal health. Around 80% of adolescents own a mobile device, and social media is frequently used by adolescents on mobile devices. Few studies have examined the use of social media as part of an intervention to promote physical activity. The purpose of this study was to evaluate the use of a Facebook group as part of a mHealth physical activity intervention trial. Adolescents, ages 14-18 years, were recruited for a four week physical activity intervention using the FitBit Flex. Participants were also given the option to join a private Facebook group where they could interact and were given badges for fitness accomplishments. The research assistant moderator posted on the Facebook group an average of 25.3 times (SD=7.2). Post-intervention, participants completed a phone interview about their experience. Of 30 intervention participants (avg age 16.0 (SD=1.1), 60.0% female), 17 opted to join the Facebook group (avg age 16.3 (SD=1.2), 47.0% female) of which 10 completed a qualitative interview. Participants averaged 4.9 interactions (SD=8.7) on the Facebook group wall throughout the intervention. From the interview responses, major themes included enjoying the badge feature of the Facebook group and wanting more content and interaction. In conclusion, participants used and enjoyed having the Facebook group, particularly the badge feature of the group, as an adjunct to the physical activity intervention. PMID- 26799888 TI - Chasing The 'Like': Adolescent Use Of Social Networking Sites In Australia. AB - The current study investigated how adolescents behave on Social Networking Sites (SNSs) and how they interpret the feedback they receive online from others. Thirty-four Australian adolescents (26 girls, 8 boys) aged 13 to 17 years participated in the study. Five semi-structured focus groups (3 mixed groups, 2 all-girl groups) were conducted to explore how adolescents perceive their own and others' SNS behaviours, the motivation underlying these behaviours, and the expected outcomes related to particular behaviours. Teenagers reported that they spend a good deal of time planning their SNS posts, felt that the information they posted was a true reflection of them as a person, and thus interpreted feedback ("likes") as measuring their self-worth. In contrast, some teenagers were perceived as "chasing the like" for status and popularity while not caring about how accurately their posts represented them as a person. A potential gender bias in these findings is discussed. PMID- 26799889 TI - Being in an Avatar: Action and Embodiment in a Digital Me. AB - This paper provides an empirical research about virtual reality users' avatar embodiment. According to literature, users that are embodied/incarnated in their avatars show a tendency to perceive avatars' failures as their own mistakes. Therefore, they are likely to monitor their own hands on the device they're using (e.g.: keyboard) when they perceive a failure in the interaction (a behavior named "focus shift"). We hypothesize that the phenomenon of focus shift is sensitive to different types of failures that can affect the multiple elements involved in the interaction. Thirty participants guided an avatar through a videogame-like virtual environment. The participants were exposed to three experimental manipulations (defective keyboard, defective avatar, defective virtual environment). We counted the number of focus shifts that participants showed in response to these three manipulated anomalies. Results showed a significantly high number of focus shifts in the condition with defective virtual environment. The findings are discussed with reference to mediation theory, explaining the role of action/feedback matching in the phenomenon of avatar embodiment. PMID- 26799890 TI - Language in Online Dating Texts: Trait Identification, Homophily, and their Effect on Attraction. AB - Research has indicated that online daters may pick up on language cues connected to personality traits in online dating profile texts, and act upon those cues. This research seeks to investigate the level of accuracy of detection of personality in dating profile texts, and the extent to which perceived or actual similarity of personality has an effect on attractiveness of the author. An online survey was conducted collecting the Ten Item Personality Inventory (TIPI) for each participant and text author, a peer-report TIPI score by participants for each text author, and an attractiveness rating on a Likert scale for each author. Participants correctly identified Extraversion, though the effect size was small. Contrary to the hypotheses, participants preferred texts when written by an author with a personality they perceived as dissimilar to their own, specifically in Openness and Conscientiousness, and no relationship was found between actual similarity of personality and attractiveness. Online daters may choose partners with complementary or desirable traits rather than similar traits, or other factors in attraction may be more salient in the initial stages of determining attraction. PMID- 26799891 TI - External Eating as a Predictor of Cue-reactivity to Food-related Virtual Environments. AB - The objective of this study was to assess the association between external eating style and food craving experienced during exposure to food cues in virtual reality (VR) environments in both clinical and non-clinical samples. According to the externality theory, people with external eating experience higher reactivity when exposed to food cues, which in turn increases the probability of overeating. Forty patients with eating disorders (23 with bulimia nervosa and 17 with binge eating disorder) and 78 undergraduate students were exposed to 10 different food cues in four VR environments (kitchen, dining room, bedroom, and cafe). After 30 seconds of exposure to each VR environment, food craving was assessed using a visual analog scale. External, emotional and restrictive eating styles were also assessed using the DEBQ. The results showed a strong association between external eating and cue-elicited food craving. After controlling for the presence of eating disorder diagnosis, external eating was the best predictor of reported food craving. The results lend support to the externality theory but highlight the need for further research in specific patterns of functioning in patients with bulimia nervosa and binge eating disorder. PMID- 26799892 TI - GETSmart: Guided Education and Training via Smart Phones to Promote Resilience. AB - Posttraumatic stress disorder (PTSD) is common in U.S. military service members (SMs) returning from Afghanistan and Iraq. SMs with PTSD symptoms that fall short of meeting full diagnostic criteria also experience devastating effects on their quality of life and daily functioning. Though evidence based treatments are indicated for those meeting diagnostic criteria, less attention has been given to interventions for those with subthreshold symptoms. The advent of novel technologies affords a unique opportunity to meet these intervention needs. Here we describe the feasibility and preliminary findings testing a smartphone-based intervention program to reduce PTSD symptoms in post-deployment SMs. Participants were randomized to a control or intervention condition. Those in the intervention condition engaged in one Skype session and six weeks of daily directive text messages guiding application (app) use. Apps primarily included those developed by the Department of Defense or VA. Participants completed the PTSD Checklist online at baseline, post-intervention, and 3-month follow-up. Overall, participant feedback was positive, regardless of treatment condition. Preliminary findings (with 10% of the overall target population having enrolled) indicate PCL scores decrease significantly from baseline to post-intervention, and these effects are maintained at 3-month follow-up. Additional analyses will be performed upon completion of the study. The present findings demonstrate the feasibility and acceptability of a smartphone-based resiliency training program for those with subthreshold PTSD. PMID- 26799893 TI - InSPAL: A Novel Immersive Virtual Learning Programme. AB - In this paper we introduce The Interactive Sensory Program for Affective Learning (InSPAL) a pioneering virtual learning programme designed for the severely intellectually disabled (SID) students, who are having cognitive deficiencies and other sensory-motor handicaps, and thus need more help and attention in overcoming their learning difficulties. Through combining and integrating interactive media and virtual reality technology with the principles of art therapy and relevant pedagogical techniques, InSPAL aims to strengthen SID students' pre-learning abilities, promote their self-awareness, decrease behavioral interferences with learning as well as social interaction, enhance their communication and thus promote their quality of life. Results of our study show that students who went through our programme were more focused, and the ability to do things more independently increased by 15%. Moreover, 50% of the students showed a marked improvement in the ability to raise their hands in response, thus increasing their communication skills. The use of therapeutic interventions enabled a better control to the body, mind and emotions, resulting a greater performance and better participation. PMID- 26799894 TI - Effect Of Telephone Calls And Text Messages On Goal Attainment In A Ehealth Coaching Service. AB - Yukendu is a personal mobile coaching service that supports people in reaching good levels of psychological and physical wellbeing through the use of an app and a telephone-based relationship with a health coach. The aim of this contribution is to describe the results obtained in a sample of 171 clients (female, n=150) and investigate the main factors in attaining their health-related goals. Results show that 61,98% (n=106) of the sample attained the results they wanted totally or partially. The regression model (number of phone calls, text messages, plan duration, achieved weight loss) accounts for 56,9% of data variance in achieved weight loss. Significant predictors of achieved weight loss are average number of calls (B=.388, p<.05), texts exchange (B=.331, p<.05) and plan duration (B=.291). These results suggest therefore that in the first phase of health behavioral change, eHealth coaching efficacy lies primarily in the communication between coach and coachee. PMID- 26799895 TI - Section V. Clinical Observations. PMID- 26799896 TI - Trait and State Craving as Indicators of Validity of VR-based Software for Binge Eating Treatment. AB - The aim of this study was to establish whether virtual reality (VR) exposure to food cues is able to produce craving levels consistent with state-craving and trait-craving as assessed by the Spanish and Italian versions of the State and Trait Food Craving Questionnaires (FCQ-T/S). The results were compared in 40 patients with eating disorders (17 with binge eating disorder, 23 with bulimia nervosa) and 78 healthy control subjects without eating disorders. Controls and patients with higher levels of trait-craving and state-craving both showed a greater desire to eat during VR exposure. Results also showed that trait and state craving assessed by FCQ-T/S were able to predict the total mean craving experienced during exposure to the VR software in both clinical and control samples. These findings present preliminary evidence about the validity of a new virtual reality-based application for cue-exposure treatment in patients with eating disorders. PMID- 26799897 TI - Robotic Companions for Older People: A Case Study in the Wild. AB - Older people tend to have difficulties using unknown technical devices and are less willing to accept technical shortcomings. Therefore, a robot that is supposed to support older people in managing daily life has to adapt to the users' needs and capabilities that are very heterogeneous within the target group. The aim of the presented case study was to provide in-depth insights on individual usage patterns and acceptance of a mobile service robot in real live environments (i.e. in the users' homes). Results from three cases (users aged 67, 78 and 85 living in their own apartments) are reported. Findings on usability and user experience illustrate that the robot has considerable potential to be accepted to support daily living at home. PMID- 26799898 TI - Movement-Based VR Gameplay Therapy For A Child With Cerebral Palsy. AB - This paper presents a single-subject feasibility study of a motion-based VR game designed to provide benefits similar to constraint-induced movement therapy for children with cerebral palsy, while providing a more enjoyable experience. The game was designed to encourage the child to perform the desired therapeutic movements by allowing him to interact with the game using only his more-affected arm. The study used an AB design: Performance across baseline and intervention phases was assessed to determine whether the intervention resulted in changes to repeated measures. Results of the study showed that compared with baseline measurements done prior to his game experience, the participant's post intervention performance showed improvement in speed of reach, dissociated movement, and bilateral integration of upper extremities in functional tasks. The child's mother, as well as one of his therapists, reported better performance outside of the study environment as well. PMID- 26799899 TI - Development Of A Virtual Environment Based On The Perceived Characteristics Of Pain In Patients With Fibromyalgia. AB - Fibromyalgia (FM) is a disorder characterized by chronic physical pain. The perception of this pain has psychological effects on mood, anxiety, and the degree of perceived control. In turn, these factors may increase the experience of pain. This study aims to develop a new virtual environment for the treatment of FM in order to enhance the therapeutic effects of traditional interventions. The first phase included a sample of 19 patients in order to identify common characteristics of the representation of pain and absence of pain, through drawing. The results showed that patients used different colors and different physical states to depict pain (red, motionless) and the absence of pain (blue, in motion). These features were then included in a 3D representation of the human body. ANOVA analysis showed that the degree of anxiety and depression influenced the perceived characteristic of movement. PMID- 26799900 TI - A Pilot Study Using Mindfulness-Guided-Relaxation & Biofeedback To Alleviate Stress In A Group. AB - The following study investigated the efficacy of a mindfulness intervention to reduce staff stress at a university in Melbourne that was undergoing a restructure and relocation. Using mindfulness guided-relaxation that incorporated positive emotions, controlled breathing and biofeedback monitors, 13 university staff recorded their sympathetic and parasympathetic activity over a four week period. They also supplied qualitative reflections of their experience. After one session of guided-relaxation and biofeedback there were significant increases in parasympathetic activity. For those people that continued practicing guided relaxation by listening to a digital recording of the session, these gains continued to increase. PMID- 26799902 TI - Section VI. Work in Progress. PMID- 26799901 TI - Rehabilitation Tool: A Pilot Study On A New Neuropsychological Interactive Training System. AB - Over the past 20 years, research has led to the development of new technologies to improve the quality of life of brain-damaged user. Introduction of new neuropsychological rehabilitation tools based both on the new knowledge on brain plasticity and on the latest developments in computer sciences is both necessary and scientifically challenging for health professionals, particularly neuropsychologists. Here we present a pilot study in which the use of a new Apple PMID- 26799903 TI - Virtual Reality for Artificial Intelligence: human-centered simulation for social science. AB - There is a long last tradition in Artificial Intelligence as use of Robots endowing human peculiarities, from a cognitive and emotional point of view, and not only in shape. Today Artificial Intelligence is more oriented to several form of collective intelligence, also building robot simulators (hardware or software) to deeply understand collective behaviors in human beings and society as a whole. Modeling has also been crucial in the social sciences, to understand how complex systems can arise from simple rules. However, while engineers' simulations can be performed in the physical world using robots, for social scientist this is impossible. For decades, researchers tried to improve simulations by endowing artificial agents with simple and complex rules that emulated human behavior also by using artificial intelligence (AI). To include human beings and their real intelligence within artificial societies is now the big challenge. We present an hybrid (human-artificial) platform where experiments can be performed by simulated artificial worlds in the following manner: 1) agents' behaviors are regulated by the behaviors shown in Virtual Reality involving real human beings exposed to specific situations to simulate, and 2) technology transfers these rules into the artificial world. These form a closed-loop of real behaviors inserted into artificial agents, which can be used to study real society. PMID- 26799904 TI - Importance of Virtual Reality to Virtual Reality Exposure Therapy, Study Design of a Randomized Trial. AB - Post Traumatic Stress Disorder (PTSD) can be a debilitating problem in service members who have served in Iraq or Afghanistan. Virtual Reality Exposure Therapy (VRET) is one of the few interventions demonstrated in randomized controlled trials to be effective for PTSD in this population. There are theoretical reasons to expect that Virtual Reality (VR) adds to the effectiveness of exposure therapy, but there is also added expense and difficulty in using VR. Described is a trial comparing outcomes from VRET and a control exposure therapy (CET) protocol in service members with PTSD. PMID- 26799905 TI - Modeling Aggression and Bullying: A Complex Systems Approach. AB - Almost daily, we read about the devastation and lasting consequences of bullying, and feel a greater impact when we hear of another child taking their life or the lives of others. What makes bullying behaviors so insidious is they cut across people, age, cultures and nations. These behaviors remain difficult to study and direct experimentation remains ethically and morally prohibitive. Therefore, we turn to computational models and simulate the natural complex social systems using the human element. If approached well, these models may yield emergent behaviors providing insight into the interactions around bullying. This paper discusses our complex systems model, and evaluates the viability of modeling bullying. Results of our implementation are described and future opportunities are identified. PMID- 26799906 TI - Confronting Auditory Hallucinations Using Virtual Reality: The Avatar Therapy. AB - The AVATAR therapy is a computer-based intervention which aims to reduce the frequency and severity of voices. The approach is based on computer technology which enables each patient to create an avatar of the entity (human or non-human) that they believe is talking to them. The therapist promotes a dialogue between the patient and the avatar in which the avatar progressively comes under the patient's control. Using real-time voice conversion delivery software, the therapist can modify the relationship between the patient and his/her voice. The innovation of this new intervention is discussed in the present paper as well as the advantages of using a computer based system. The subjective view of the technology from a participant's point of view is also presented. PMID- 26799907 TI - NO-FEAR Airlines: A Computer-aided Self-help Treatment for Flying Phobia. AB - In vivo exposure is the treatment of choice for specific phobias. However, this treatment is linked to a number of limitations in its implementation. Therefore, it is important to develop strategies for improving treatment adherence, acceptance, and dissemination of evidence-based treatments. Information and Communication Technologies, specifically, computerized programs boast advantages in treating flying phobia. NO-FEAR Airlines is a Computer-aided Self-help Treatment for this problem, which can be self-applied via Internet. NO-FEAR Airlines treatment protocol comprises three therapeutic components: psychoeducation, exposure and overlearning. Exposure is carried out through 6 scenarios that are composed by images and real sounds related to a flight in process. The aim of the present work is to describe NO-FEAR Airlines program. PMID- 26799908 TI - Human Instruments: Accessible Musical Instruments for People with Varied Physical Ability. AB - There are few ways in which persons, who do not have the use of their hands or arms, are able make music or control complex computer systems. Music as an expressive output is key to the full development of the human mind. Human Instruments is dedicated to the development and production of accessible musical instruments playable at a professional level, as well as computer control interfaces. We are currently user-testing three new, uniquely accessible devices, for their effectiveness in expressive music creation. Preliminary results are compelling. PMID- 26799909 TI - Presence at a distance. AB - Nowadays in the context of the cyberculture, computer-mediated inter-subjective relationships are part of our everyday lives, in both the professional and personal spheres, and for all age groups. In the clinical field, many applications have been developed to facilitate the exchange of informations and mediate the relationship between patient and therapist. In psychology, more or less immersive technologies are used, to encourage the feeling of presence among the users, and to trigger certain psychological processes. In our research, we have explored the remote clinical interview through videoconferencing, with the development and utilisation of the iPSY platform, totally focused on this objective. In this context, we have considered the notion of intersubjectivity, despite the physical absence. This research is leading us today to envision the notions of distance and presence, and possibly to redefine them. Thus, can we still oppose physical distance to psychological distance? Can we still affirm that the physical absence does not permit a psychological co-presence in certain interactions, like this observed in video interviews? The results show that the psychological processes, activated in this context, are similar to those observed in "traditional" clinical consults between the patient and the therapist. However, certain specifics have led us to consider the concept of distance, here influenced by the framework, and to observe its effects. This distance could possibly constitute a therapeutic lever for some patients, notably for those who have difficulties establishing the right psychological distance in their relationships with others. According to these results, can "distance" still be opposed to "presence", or could it be re-defined? This also opens up questions on the more general concept of digital relationships, and the definition of their specificities. PMID- 26799913 TI - Dartmouth Atlas Area-Level Estimates of End-of-Life Expenditures: How Well Do They Reflect Expenditures for Prospectively Identified Advanced Lung Cancer Patients? AB - OBJECTIVE: Assess validity of the retrospective Dartmouth hospital referral region (HRR) end-of-life spending measures by comparing with health care expenditures from diagnosis to death for prospectively identified advanced lung cancer patients. DATA/SETTING/DESIGN: We calculated health care spending from diagnosis (2003-2005) to death or through 2011 for 885 patients aged >=65 years with advanced lung cancer using Medicare claims. We assessed the association between Dartmouth HRR-level spending in the last 2 years of life and patient level spending using linear regression with random HRR effects, adjusting for patient characteristics. FINDINGS: For each $1 increase in the Dartmouth metric, spending for our cohort increased by $0.74 (p < .001). The Dartmouth spending variable explained 93.4 percent of the HRR-level variance in observed spending. CONCLUSIONS: HRR-level spending estimates for deceased patient cohorts reflect area-level care intensity for prospectively identified advanced lung cancer patients. PMID- 26799915 TI - Theory of Graphene Raman Scattering. AB - Raman scattering plays a key role in unraveling the quantum dynamics of graphene, perhaps the most promising material of recent times. It is crucial to correctly interpret the meaning of the spectra. It is therefore very surprising that the widely accepted understanding of Raman scattering, i.e., Kramers-Heisenberg-Dirac theory, has never been applied to graphene. Doing so here, a remarkable mechanism we term"transition sliding" is uncovered, explaining the uncommon brightness of overtones in graphene. Graphene's dispersive and fixed Raman bands, missing bands, defect density and laser frequency dependence of band intensities, widths of overtone bands, Stokes, anti-Stokes anomalies, and other known properties emerge simply and directly. PMID- 26799916 TI - Toward a detailed understanding of search trajectories in fragment assembly approaches to protein structure prediction. AB - Energy functions, fragment libraries, and search methods constitute three key components of fragment-assembly methods for protein structure prediction, which are all crucial for their ability to generate high-accuracy predictions. All of these components are tightly coupled; efficient searching becomes more important as the quality of fragment libraries decreases. Given these relationships, there is currently a poor understanding of the strengths and weaknesses of the sampling approaches currently used in fragment-assembly techniques. Here, we determine how the performance of search techniques can be assessed in a meaningful manner, given the above problems. We describe a set of techniques that aim to reduce the impact of the energy function, and assess exploration in view of the search space defined by a given fragment library. We illustrate our approach using Rosetta and EdaFold, and show how certain features of these methods encourage or limit conformational exploration. We demonstrate that individual trajectories of Rosetta are susceptible to local minima in the energy landscape, and that this can be linked to non-uniform sampling across the protein chain. We show that EdaFold's novel approach can help balance broad exploration with locating good low-energy conformations. This occurs through two mechanisms which cannot be readily differentiated using standard performance measures: exclusion of false minima, followed by an increasingly focused search in low-energy regions of conformational space. Measures such as ours can be helpful in characterizing new fragment-based methods in terms of the quality of conformational exploration realized. PMID- 26799918 TI - Emotion and dissociative seizures: A phenomenological analysis of patients' perspectives. AB - Quantitative research has indicated that patients with dissociative seizures (DS) show altered responses to emotional stimuli, in addition to considerable emotional distress and dysregulation. The present study sought to further explore emotional processes in this population, to extend previous findings, and to provide a phenomenological insight into patients' perspectives on these issues. Semistructured interviews were carried out with 15 patients with DS, and the principles of interpretative phenomenological analysis (IPA) were adopted in data analysis. Key themes elicited included: i) general emotional functioning; ii) adverse (stressful/traumatic) life experiences; iii) the role of emotions in DS; iv) relating to others; and v) resilience, protective factors, and coping mechanisms. The clinical and theoretical implications of the findings are discussed. PMID- 26799917 TI - Trimerization of the HIV Transmembrane Domain in Lipid Bilayers Modulates Broadly Neutralizing Antibody Binding. AB - The membrane-proximal external region (MPER) of HIV gp41 is an established target of antibodies that neutralize a broad range of HIV isolates. To evaluate the role of the transmembrane (TM) domain, synthetic MPER-derived peptides were incorporated into lipid nanoparticles using natural and designed TM domains, and antibody affinity was measured using immobilized and solution-based techniques. Peptides incorporating the native HIV TM domain exhibit significantly stronger interactions with neutralizing antibodies than peptides with a monomeric TM domain. Furthermore, a peptide with a trimeric, three-helix bundle TM domain recapitulates the binding profile of the native sequence. These studies suggest that neutralizing antibodies can bind the MPER when the TM domain is a three helix bundle and this presentation could influence the binding of neutralizing antibodies to the virus. Lipid-bilayer presentation of viral antigens in Nanodiscs is a new platform for evaluating neutralizing antibodies. PMID- 26799922 TI - Rapid sensory-directed methodology for the selection of high-quality aroma wines. AB - BACKGROUND: The present work contributes by developing a rapid sensory-directed methodology for the screening and selection of high-quality wines with different sensory profiles. Verdejo and Tempranillo musts were fermented with 50 different yeasts each under controlled laboratory conditions. Resulting samples were firstly categorised according to five levels of quality by a panel of wine professionals. Higher quality samples were described by flash profiling by a semi trained panel and most distinctive samples were screened by gas chromatography olfactometry (GC-O). RESULTS: Seven Verdejo and five Tempranillo samples were classified in the highest quality category, presenting different aroma profiles such as citrus, fruit in syrup, boxtree/vegetal, tropical or wet grain aromas for Verdejo and red fruit or fruit in syrup for Tempranillo. beta-Damascenone, 3 mercaptohexyl acetate and ethyl butyrate appeared as distinctive quality compounds linked to dried, tropical and red fruit aromas, respectively. CONCLUSIONS: The categorisation task followed by flash profiling and GC-O analysis was shown to be a rapid and effective sensory-directed methodology for the screening of distinctive and quality wine aroma profiles in a case study of yeast selection. The wine industry could benefit from the use of this methodology as a complementary tool for optimising different technical processes. (c) 2016 Society of Chemical Industry. PMID- 26799921 TI - The plastic cellular states of liver cells: Are EpCAM and Lgr5 fit for purpose? AB - Adult liver cells have been considered restricted regarding their fate and lineage potential. That is, hepatocytes have been thought able only to generate hepatocytes and duct cells, only duct cells. While this may be the case for the majority of scenarios in a state of quiescence or homeostasis, evidence suggests that liver cells are capable of interconverting between cellular states of distinct phenotypic traits. This interconversion or plasticity had been suggested by classical studies using cellular markers, but recently lineage tracing approaches have proven that cells are highly plastic and retain an extraordinary ability to respond differently to normal tissue homeostasis, to tissue repair, or when challenged to expand ex vivo or to differentiate upon transplantation. Stemness, as "self-renewal and multipotency," seems not to be limited to a particular cell type but rather to a cellular state in which cells exhibit a high degree of plasticity and can move back and forth in different phenotypic states. For instance, upon damage cells can dedifferentiate to acquire stem cell potential that allows them to self-renew, repopulate a damaged tissue, and then undergo differentiation. In this review, we will discuss the evidence on cellular plasticity in the liver, focusing our attention on two markers, epithelial cell adhesion molecule and leucine-rich repeat-containing G protein-coupled receptor 5, which identify cells with stem cell potential. (Hepatology 2016;64:652-662). PMID- 26799923 TI - Goltz syndrome and PORCN: A view from Europe. AB - Goltz syndrome (focal dermal hypoplasia) is an X-linked dominant, multisystem birth defect with lethality for male embryos. The hypoplastic skin lesions follow Blaschko's lines and often show herniation of subcutaneous fatty tissue. Extracutaneous defects mainly involve the brain, the bones, the teeth, and the eyes. All of these anomalies show a segmental arrangement reflecting functional X chromosome mosaicism. The present contribution tells the story how the molecular cause of Goltz syndrome was investigated and found by the group of the geneticist Karl-Heinz Grzeschik from Marburg, Germany. PMID- 26799924 TI - Philadelphia-positive dimorphic blasts in mixed-phenotype acute leukemia with TET2 mutation. PMID- 26799926 TI - Multiomics approach to identify novel biomarkers for dilated cardiomyopathy: Proteome and transcriptome analyses of 4C30 dilated cardiomyopathy mouse model. AB - Dilated cardiomyopathy (DCM) is an intractable disease, without any radical treatment option other than cardiac transplantation. Additionally, biomarkers to determine progressive staging are not yet available. Irrespective of the diversity of causative gene mutations, the phenotype of DCM is rather common. Therefore, it is plausible to determine DCM staging in terms of variations in protein and mRNA levels. In this study, we performed proteome and transcriptome analysis of the left ventricle of 4C30 DCM model mice showing mild and severe phenotypes at 12 and 24 weeks (wk) after birth, respectively. Proteomic analyses results showed 109 proteins that increased and 133 others that decreased among 1874 detected proteins. We selected biomarker candidates by confirming consistent alterations in protein levels at 12 and 24 wk, and mRNA levels at 12 wk, and narrowed these down based on the requirement that they should be detectable in blood. Finally, we selected six biomarker candidates based on sustained or augmented alteration at 24 wk and confirmed their definite alterations in the left ventricle by quantitative polymerase chain reaction, western blot analysis, and multiple reaction monitoring (MRM). To assess the validity of this strategy, we measured plasma concentrations of the six candidates by MRM method and identified two proteins (FTL1 and GRP78) that demonstrated significant elevation in the 4C30 mice plasma. Taken together, a multiomics strategy comparing tissue expression levels of proteins and mRNAs between diseased and control groups, with appropriate confirmation, is a promising approach for the discovery of new biomarkers. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 491-502, 2016. PMID- 26799925 TI - A Non-Newtonian Fluid Robot. AB - New types of robots inspired by biological principles of assembly, locomotion, and behavior have been recently described. In this work we explored the concept of robots that are based on more fundamental physical phenomena, such as fluid dynamics, and their potential capabilities. We report a robot made entirely of non-Newtonian fluid, driven by shear strains created by spatial patterns of audio waves. We demonstrate various robotic primitives such as locomotion and transport of metallic loads-up to 6-fold heavier than the robot itself-between points on a surface, splitting and merging, shapeshifting, percolation through gratings, and counting to 3. We also utilized interactions between multiple robots carrying chemical loads to drive a bulk chemical synthesis reaction. Free of constraints such as skin or obligatory structural integrity, fluid robots represent a radically different design that could adapt more easily to unfamiliar, hostile, or chaotic environments and carry out tasks that neither living organisms nor conventional machines are capable of. PMID- 26799927 TI - Scholarly development for primary care residents. AB - BACKGROUND: Development, evaluation and dissemination of primary care innovations are essential for the future of health care; however, primary care physicians including family physician, lag behind hospital-based physicians in research productivity. Family medicine residencies struggle to implement scholarly skills training programmes for busy family physicians. The Primary Care Scholarly Development Program (PC-SDP) aimed to empower residents to incorporate innovation with scholarship into future practice, by facilitating successful resident scholarly projects and reducing perceived barriers. METHODS: Educational intervention. The required PC-SDP was piloted through a family medicine residency programme in the USA. Key elements included: rigorous but achievable requirements; emphasis on Boyer's scholarship of application, teaching and discovery; resident engagement, through the support of their 'professional passions'; basic research training; multilevel mentoring; and modest curriculum time. EVALUATION: A mixed-methods longitudinal evaluation included: (1) a qualitative study of intervention class; (2) assessing the scholarly output of the intervention class versus the comparison class; and (3) a follow-up survey of both groups after 3 or 4 years. RESULTS: Data were analysed from all 25 residents in the classes of 2008 and 2009 (12 intervention; 13 comparison). Qualitative interviews of residents from the intervention group revealed that their initial feelings of trepidation about scholarly work gave way to feelings of accomplishment and confidence in their ability to integrate scholarship into busy careers. Residents in the intervention group had a greater volume of scholarly output at graduation, and follow-up surveys suggest that they value incorporating scholarship into their careers more so than physicians from the comparison group. DISCUSSION: The PC-SDP seems to foster enthusiasm for scholarship by supporting residents' professional passions and facilitating successful projects. This may foster improved participation in scholarship in future clinical practice. Primary care physicians, including family physicians, lag behind hospital-based physicians in research productivity. PMID- 26799928 TI - Effect of Integration Patterns Around Implant Neck on Stress Distribution in Peri Implant Bone: A Finite Element Analysis. AB - PURPOSE: To investigate the biomechanical performance of different osseointegration patterns between cortical bone and implants using finite element analysis. MATERIALS AND METHODS: Fifteen finite element models were constructed of the mandibular fixed prosthesis supported by implants. Masticatory loads (200 N axial, 100 N oblique, 40 N horizontal) were applied. The cortical bone/implant interface was divided equally into four layers: upper, upper-middle, lower middle, and lower. The bone stress and implant displacement were calculated for 5 degrees of uniform integration (0, 20%, 40%, 60%, and 100%) and 10 integration patterns. RESULTS: The stress was concentrated in the bone margin and gradually decreased as osseointegration progressed, when the integrated and nonintegrated areas were alternated on the bone-implant surface. Compared with full integration, the integration of only the lower-middle layer or lower half layers significantly decreased von Mises, tensile, and compressive stresses in cortical bone under oblique and horizontal loads, and these patterns did not induce higher stress in the cancellous bone. For the integration of only the upper or upper middle layer, stress in the cortical and cancellous bones significantly increased and was considerably higher than in the case of nonintegration. In addition, the maximum stress in the cortical bone was sensitive to the quantity of integrated nodes at the bone margin; lower quantity was associated with higher stress. There was no significant difference in the displacement of implants among 15 models. CONCLUSIONS: Integration patterns of cortical bone significantly affect stress distribution in peri-implant bone. The integration of only the lower-middle or lower half layers helps to increase the load-bearing capacity of peri-implant bone and decrease the risk of overloading, while upper integration may further increase the risk of bone resorption. PMID- 26799929 TI - Coalho Cheese Made with Protease from Thermomucor indicae-seudaticae N31: Technological Potential of the New Coagulant for the Production of High-Cooked Cheese. AB - The aim of this study was to explore the use of a new coagulant from Thermomucor indicae-seudaticae N31 for the manufacture of a high-cooked starter-free cheese variety, by evaluating its physicochemical and functional characteristics in comparison to cheeses made with a traditional commercial coagulant. Coalho cheese was successfully produced with the new protease as it exhibited comparable characteristics to the one produced using the commercial enzyme: pH behavior during manufacture; cheese composition; protein and fat recovery; and cheese yield. In addition, during storage, melting was low and not affected by storage time; the increase of TCA 12% soluble nitrogen (% of total nitrogen) was lower than half of that of pH 4.6 soluble nitrogen (% of total nitrogen); concentration of beta-CN significantly decreased, whereas alphas1 -CN concentration was not affected by storage time. PMID- 26799932 TI - Evaluation and management of intrahepatic and extrahepatic cholangiocarcinoma. AB - Cholangiocarcinomas are rare biliary tract tumors that are often challenging to diagnose and treat. Cholangiocarcinomas are generally categorized as intrahepatic or extrahepatic depending on their anatomic location. The majority of patients with cholangiocarcinoma do not have any of the known or suspected risk factors and present with advanced disease. The optimal evaluation and management of patients with cholangiocarcinoma requires thoughtful integration of clinical information, imaging studies, cytology and/or histology, as well as prompt multidisciplinary evaluation. The current review focuses on recent advances in the diagnosis and treatment of patients with cholangiocarcinoma and, in particular, on the role of endoscopy, surgery, transplantation, radiotherapy, systemic therapy, and liver-directed therapies in the curative or palliative treatment of these individuals. Cancer 2016;122:1349-1369. (c) 2016 American Cancer Society. PMID- 26799934 TI - Understanding the Mechanism of the Divergent Reactivity of Non-Heteroatom Stabilized Chromium Carbene Complexes with Furfural Imines: Formation of Benzofurans and Azetines. AB - The mechanisms of the reaction between non-heteroatom-stabilized alkynyl chromium carbene complexes prepared in situ and furfural imines to yield benzofurans and/or azetines have been explored by means of density functional theory method calculations. The reaction proceeds through a complex cascade of steps triggered by a nucleophilic addition of the imine nitrogen atom. The formation of two benzofuran regioisomers has been explained in terms of competitive nucleophilic attacks to different positions of the carbene complex. Each of these regioisomers can be obtained as the major product depending on the starting materials. The overall sequence could be controlled to yield benzofurans or azetines by adjusting the substituents present in the initial carbene complex. This mechanistic information allowed for the preparation of new benzofurans and azetinylcarbenes in good yields. PMID- 26799933 TI - MicroRNA-134 Contributes to Glucose-Induced Endothelial Cell Dysfunction and This Effect Can Be Reversed by Far-Infrared Irradiation. AB - Diabetes mellitus (DM) is a metabolic disease that is increasing worldwide. Furthermore, it is associated with the deregulation of vascular-related functions, which can develop into major complications among DM patients. Endothelial colony forming cells (ECFCs) have the potential to bring about medical repairs because of their post-natal angiogenic activities; however, such activities are impaired by high glucose- (HG) and the DM-associated conditions. Far-infrared radiation (FIR) transfers energy as heat that is perceived by the thermoreceptors in human skin. Several studies have revealed that FIR improves vascular endothelial functioning and boost angiogenesis. FIR has been used as anti-inflammatory therapy and as a clinical treatment for peripheral circulation improvement. In addition to vascular repair, there is increasing evidence to show that FIR can be applied to a variety of diseases, including cardiovascular disorders, hypertension and arthritis. Yet mechanism of action of FIR and the biomarkers that indicate FIR effects remain unclear. MicroRNA-134 (miR-134-5p) was identified by small RNA sequencing as being increased in high glucose (HG) treated dfECFCs (HG-dfECFCs). Highly expressed miR-134 was also validated in dmECFCs by RT-qPCR and it is associated with impaired angiogenic activities of ECFCs. The functioning of ECFCs is improved by FIR treatment and this occurs via a reduction in the level of miR-134 and an increase in the NRIP1 transcript, a direct target of miR-134. Using a mouse ischemic hindlimb model, the recovery of impaired blood flow in the presence of HG-dfECFCs was improved by FIR pretreatment and this enhanced functionality was decreased when there was miR-134 overexpression in the FIR pretreated HG-dfECFCs. In conclusion, our results reveal that the deregulation of miR-134 is involved in angiogenic defects found in DM patients. FIR treatment improves the angiogenic activity of HG-dfECFCs and dmECFCs and FIR has potential as a treatment for DM. Detection of miR-134 expression in FIR-treated ECFCs should help us to explore further the effectiveness of FIR therapy. PMID- 26799935 TI - Zebra Stripes through the Eyes of Their Predators, Zebras, and Humans. AB - The century-old idea that stripes make zebras cryptic to large carnivores has never been examined systematically. We evaluated this hypothesis by passing digital images of zebras through species-specific spatial and colour filters to simulate their appearance for the visual systems of zebras' primary predators and zebras themselves. We also measured stripe widths and luminance contrast to estimate the maximum distances from which lions, spotted hyaenas, and zebras can resolve stripes. We found that beyond ca. 50 m (daylight) and 30 m (twilight) zebra stripes are difficult for the estimated visual systems of large carnivores to resolve, but not humans. On moonless nights, stripes are difficult for all species to resolve beyond ca. 9 m. In open treeless habitats where zebras spend most time, zebras are as clearly identified by the lion visual system as are similar-sized ungulates, suggesting that stripes cannot confer crypsis by disrupting the zebra's outline. Stripes confer a minor advantage over solid pelage in masking body shape in woodlands, but the effect is stronger for humans than for predators. Zebras appear to be less able than humans to resolve stripes although they are better than their chief predators. In conclusion, compared to the uniform pelage of other sympatric herbivores it appears highly unlikely that stripes are a form of anti-predator camouflage. PMID- 26799936 TI - The Orientations of Large Aspect-Ratio Coiled-Coil Proteins Attached to Gold Nanostructures. AB - Methods for patterning biomolecules on a substrate at the single molecule level have been studied as a route to sensors with single-molecular sensitivity or as a way to probe biological phenomena at the single-molecule level. However, the arrangement and orientation of single biomolecules on substrates has been less investigated. Here, the arrangement and orientation of two rod-like coiled-coil proteins, cortexillin and tropomyosin, around patterned gold nanostructures is examined. The high aspect ratio of the coiled coils makes it possible to study their orientations and to pursue a strategy of protein orientation via two-point attachment. The proteins are anchored to the surfaces using thiol groups, and the number of cysteine residues in tropomyosin is varied to test how this variation affects the structure and arrangement of the surface-attached proteins. Molecular dynamics studies are used to interpret the observed positional distributions. Based on initial studies of protein attachment to gold post structures, two 31-nm long tropomyosin molecules are aligned between the two sidewalls of a trench with a width of 68 nm. Because the approach presented in this study uses one of twenty natural amino acids, this method provides a convenient way to pattern biomolecules on substrates using standard chemistry. PMID- 26799937 TI - Sarcopenia and frailty in older patients with diabetes mellitus. AB - Sarcopenia is defined as age-associated loss of muscle mass and function, and is frequently accompanied by diabetes mellitus (DM) in older adults. Some of the mechanisms of the development of sarcopenia including insulin resistance, chronic inflammation and mitochondrial dysfunction are also associated with the pathogenesis of DM. Sarcopenia provides the basis for frailty, which is a state that is highly vulnerable to stressors, and can lead to disability, dependency and mortality, and older DM patients are often in a state of frailty. Given the background of an increasing number of older DM patients, the screening and early detection of sarcopenia/frailty and appropriate intervention would be expected to improve the prognosis and quality of life in older patients. PMID- 26799939 TI - Characterization and application of lactic acid bacteria for tropical silage preparation. AB - Strains TH 14, TH 21 and TH 64 were isolated from tropical silages, namely corn stover, sugar cane top and rice straw, respectively, prepared in Thailand. These strains were selected by low pH growth range and high lactic acid-producing ability, similar to some commercial inoculants. Based on the analysis of 16S ribosomal RNA gene sequence and DNA-DNA relatedness, strain TH 14 was identified as Lactobacillus casei, and strains TH 21 and TH 64 were identified as L. plantarum. Strains TH 14, TH 21, TH 64 and two commercial inoculants, CH (L. plantarum) and SN (L. rhamnosus), were used as additives to fresh and wilted purple Guinea and sorghum silages prepared using a small-scale fermentation method. The number of epiphytic lactic acid bacteria (LAB) in the forages before ensilage was relatively low but the numbers of coliform and aerobic bacteria were higher. Sorghum silages at 30 days of fermentation were all well preserved with low pH (3.56) and high lactic acid production (72.86 g/kg dry matter). Purple Guinea silage inoculated with LAB exhibited reduced count levels of aerobic and coliform bacteria, lower pH, butyric acid and ammonia nitrogen and increased lactic acid concentration, compared with the control. Strain TH 14 more effectively improved lactic acid production compared with inoculants and other strains. (c) 2016 Japanese Society of Animal Science. PMID- 26799938 TI - Gradient Index Microlens Implanted in Prefrontal Cortex of Mouse Does Not Affect Behavioral Test Performance over Time. AB - Implanted gradient index lenses have extended the reach of standard multiphoton microscopy from the upper layers of the mouse cortex to the lower cortical layers and even subcortical regions. These lenses have the clarity to visualize dynamic activities, such as calcium transients, with subcellular and millisecond resolution and the stability to facilitate repeated imaging over weeks and months. In addition, behavioral tests can be used to correlate performance with observed changes in network function and structure that occur over time. Yet, this raises the questions, does an implanted microlens have an effect on behavioral tests, and if so, what is the extent of the effect? To answer these questions, we compared the performance of three groups of mice in three common behavioral tests. A gradient index lens was implanted in the prefrontal cortex of experimental mice. We compared their performance with mice that had either a cranial window or a sham surgery. Three presurgical and five postsurgical sets of behavioral tests were performed over seven weeks. Behavioral tests included rotarod, foot fault, and Morris water maze. No significant differences were found between the three groups, suggesting that microlens implantation did not affect performance. The results for the current study clear the way for combining behavioral studies with gradient index lens imaging in the prefrontal cortex, and potentially other regions of the mouse brain, to study structural, functional, and behavioral relationships in the brain. PMID- 26799942 TI - Omega-3 Fatty Acids for Depression in Multiple Sclerosis: A Randomized Pilot Study. AB - Multiple sclerosis is the most common chronic disabling disease in the central nervous system in young to middle aged adults. Depression is common in multiple sclerosis (MS) affecting between 50-60% of patients. Pilot studies in unipolar depression report an improvement in depression when omega-3 fatty acids are given with antidepressants. The objective of this study was to investigate whether omega-3 fatty acid supplementation, as an augmentation therapy, improves treatment-resistant major depressive disorder (MDD) in people with MS. We performed a randomized, double-blind, placebo-controlled pilot study of omega-3 fatty acids at six grams per day over three months. The primary outcome was a 50% or greater improvement on the Montgomery-Asberg Depression Rating Scale (MADRS). Thirty-nine participants were randomized and thirty-one completed the 3-month intervention. Improvement on MADRS between groups was not significantly different at the 3-month end point with 47.4% in the omega-3 fatty acid group and 45.5% in the placebo group showing 50% or greater improvement (p = 0.30). Omega-3 fatty acids as an augmentation therapy for treatment-resistant depression in MS was not significantly different than placebo in this pilot trial. Omega-3 fatty acid supplementation at the dose given was well-tolerated over 3 months. TRIAL REGISTRATION: ClinicalTrials.gov NCT00122954. PMID- 26799943 TI - Diagnostic clues for FNA diagnosis of intranodal palisaded myofibroblastoma, a rare benign lesion, an introspective case report. AB - Intranodal palisaded myofibroblastoma (IPM) is a benign entity, characterized by intranodal proliferation of cells of myofibroblastic origin. It has five distinct histologic features: compressed remnants of lymphoid tissue at the periphery, spindle cells with nuclear palisading, intralesional hemorrhage, amianthoid fibers, and intracellular and extracellular fuchsinophilic bodies. The spindle cells are SMA and vimentin (IHC) positive and are negative for S 100, and has a low proliferative index. Cytologic diagnosis of this lesion is a diagnostic challenge and has to be differentiated from other stroma rich lesions including schwannoma. The FNA smears were reviewed after histopathology to look for any specific features. This report highlights the variable character of spindle cells, presence of unique "amanthiod fibers" and blood vessel within cell clusters in MGG stained FNA smears, which can be a useful diagnostic clue. This observation is being reported for the first time. PMID- 26799944 TI - Ameliorative Effect of Grape Seed Proanthocyanidin Extract on Cadmium-Induced Meiosis Inhibition During Oogenesis in Chicken Embryos. AB - Cadmium (Cd) is an environmental endocrine disruptor that has toxic effects on the female reproductive system. Here the ameliorative effect of grape seed proanthocyanidin extract (GSPE) on Cd-induced meiosis inhibition during oogenesis was explored. As compared with controls, chicken embryos exposed to Cd (3 ug/egg) displayed a changed oocyte morphology, decreased number of meiotic germ cells, and decreased expression of the meiotic marker protein gammaH2AX. Real time RT PCR also revealed a significant down-regulation in the mRNA expressions of various meiosis-specific markers (Stra8, Spo11, Scp3, and Dmc1) together with those of Raldh2, a retinoic acid (RA) synthetase, and of the receptors (RARalpha and RARbeta). In addition, exposure to Cd increased the production of H2 O2 and malondialdehyde in the ovaries and caused a corresponding reduction in glutathione and superoxide dismutase. Simultaneous supplementation of GSPE (150 ug/egg) markedly alleviated the aforementioned Cd-induced embryotoxic effects by upregulating meiosis-related proteins and gene expressions and restoring the antioxidative level. Collectively, the findings provided novel insights into the underlying mechanism of Cd-induced meiosis inhibition and indicated that GSPE might potentially ameliorate related reproductive disorders. PMID- 26799945 TI - Prostate-specific antigen patterns in US and European populations: comparison of six diverse cohorts. AB - OBJECTIVE: To determine whether there are differences in prostate-specific antigen (PSA) levels at diagnosis or changes in PSA levels between US and European populations of men with and without prostate cancer (PCa). SUBJECTS AND METHODS: We analysed repeated measures of PSA from six clinically and geographically diverse cohorts of men: two cohorts with PSA-detected PCa, two cohorts with clinically detected PCa and two cohorts without PCa. Using multilevel models, average PSA at diagnosis and PSA change over time were compared among study populations. RESULTS: The annual percentage PSA change of 4 5% was similar between men without cancer and men with PSA-detected cancer. PSA at diagnosis was 1.7 ng/mL lower in a US cohort of men with PSA-detected PCa (95% confidence interval 1.3-2.0 ng/mL), compared with a UK cohort of men with PSA detected PCa, but there was no evidence of a different rate of PSA change between these populations. CONCLUSION: We found that PSA changes over time are similar in UK and US men diagnosed through PSA testing and even in men without PCa. Further development of PSA models to monitor men on active surveillance should be undertaken in order to take advantage of these similarities. We found no evidence that guidelines for using PSA to monitor men cannot be passed between US and European studies. PMID- 26799948 TI - Pd Nanocubes@ZIF-8: Integration of Plasmon-Driven Photothermal Conversion with a Metal-Organic Framework for Efficient and Selective Catalysis. AB - Composite nanomaterials usually possess synergetic properties resulting from the respective components and can be used for a wide range of applications. In this work, a Pd nanocubes@ZIF-8 composite material has been rationally fabricated by encapsulation of the Pd nanocubes in ZIF-8, a common metal-organic framework (MOF). This composite was used for the efficient and selective catalytic hydrogenation of olefins at room temperature under 1 atm H2 and light irradiation, and benefits from plasmonic photothermal effects of the Pd nanocube cores while the ZIF-8 shell plays multiple roles; it accelerates the reaction by H2 enrichment, acts as a "molecular sieve" for olefins with specific sizes, and stabilizes the Pd cores. Remarkably, the catalytic efficiency of a reaction under 60 mW cm(-2) full-spectrum or 100 mW cm(-2) visible-light irradiation at room temperature turned out to be comparable to that of a process driven by heating at 50 degrees C. Furthermore, the catalyst remained stable and could be easily recycled. To the best of our knowledge, this work represents the first combination of the photothermal effects of metal nanocrystals with the favorable properties of MOFs for efficient and selective catalysis. PMID- 26799947 TI - NlpC/P60 domain-containing proteins of Mycobacterium avium subspecies paratuberculosis that differentially bind and hydrolyze peptidoglycan. AB - A subset of proteins containing NlpC/P60 domains are bacterial peptidoglycan hydrolases that cleave noncanonical peptide linkages and contribute to cell wall remodeling as well as cell separation during late stages of division. Some of these proteins have been shown to cleave peptidoglycan in Mycobacterium tuberculosis and play a role in Mycobacterium marinum virulence of zebra fish; however, there are still significant knowledge gaps concerning the molecular function of these proteins in Mycobacterium avium subspecies paratuberculosis (MAP). The MAP genome sequence encodes five NlpC/P60 domain-containing proteins. We describe atomic resolution crystal structures of two such MAP proteins, MAP_1272c and MAP_1204. These crystal structures, combined with functional assays to measure peptidoglycan cleavage activity, led to the observation that MAP_1272c does not have a functional catalytic core for peptidoglycan hydrolysis. Furthermore, the structure and sequence of MAP_1272c demonstrate that the catalytic residues normally required for hydrolysis are absent, and the protein does not bind peptidoglycan as efficiently as MAP_1204. While the NlpC/P60 catalytic triad is present in MAP_1204, changing the catalytic cysteine-155 residue to a serine significantly diminished catalytic activity, but did not affect binding to peptidoglycan. Collectively, these findings suggest a broader functional repertoire for NlpC/P60 domain-containing proteins than simply hydrolases. PMID- 26799652 TI - Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). PMID- 26799950 TI - Albumin (BSA) Adsorption over Graphene in Aqueous Environment: Influence of Orientation, Adsorption Protocol, and Solvent Treatment. AB - We report 150 ns explicit solvent MD simulations of the adsorption on graphene of albumin (BSA) in two orientations and using two different adsorption protocols, i.e., free and forced adsorption. Our results show that free adsorption occurs with little structural rearrangements. Even taking adsorption to an extreme, by forcing it with a 5 nN downward force applied during the initial 20 ns, we show that along a particular orientation BSA is able to preserve the structural properties of the majority of its binding sites. Furthermore, in all the cases considered in this work, the ibuprofen binding site has shown a strong resilience to structural changes. Finally, we compare these results with implicit solvent simulations and find that the latter predicts an extreme protein unfolding upon adsorption. The origin of this discrepancy is attributed to a poor description of the water entropic forces at interfaces in the implicit solvent methods. PMID- 26799953 TI - Dying at home or in the hospital? An observational study in German general practice. AB - BACKGROUND: Although determinants of place of death have been investigated in several studies, there is a lack of knowledge on factors associated with dying at home from the general practice perspective. OBJECTIVES: To identify factors associated with dying at home for patients in German general practice. METHODS: In a retrospective study, general practitioners of 30 general practices were asked to provide data for all patients aged 18 years or older who died within the last 12 months, using a self-developed questionnaire. 'Dying in hospital' was defined as dying in hospital or hospice and 'dying at home' as dying at one's usual residence including the nursing home. Multiple logistic regression analyses were used to determine factors associated with 'dying at home'; odds ratios (ORs) and their 95% confidence intervals (CI) were calculated as measures of effect size. RESULTS: Of 439 deceased patients, 52.2% died at home, and 47.8% died in hospital or hospice. Determinants for dying at home were patients' care in the last 48 hours of life by family members (OR: 7.8, 95% CI: 3.4-18.0), by general practitioners (GPs) (OR: 7.3, 4.2-12.9) and living in a nursing home (OR: 3.8, 1.7-8.3). In the adjusted model, low comorbidity was positively associated (OR: 3.2, 1.4-7.0), and low functional health status (Karnofsky performance status) was negatively associated with dying at home (OR: 0.3, 0.1-0.7). CONCLUSION: Apart from patient-related factors such as comorbidity and health status, care by family members and GPs respectively, were determinants of dying at home. PMID- 26799961 TI - A simple synthesis of hollow Mn2O3 core-shell microspheres and their application in lithium ion batteries. AB - Hollow Mn2O3 core-shell microspheres were successfully fabricated via a mixed method including a solution method and a subsequent thermal decomposition. Transmission electron microscopy showed that the average size of Mn2O3 cores was about 0.8 MUm and their shell thickness was 120 nm. These hollow Mn2O3 core-shell microspheres as anode materials exhibited a high specific capacity of up to 620 mA h g(-1) with a good cycling performance (500 cycles), indicating that the hollow Mn2O3 core-shell microsphere material was a promising anode candidate for a high-capacity, low-cost, and environment-friendly lithium ion battery. The formation mechanism was studied in detail. PMID- 26799954 TI - Evaluation of protective effects of diosmin (a citrus flavonoid) in chemical induced urolithiasis in experimental rats. AB - Context There have not been any conclusive studies of the effects of diosmin, a modified flavanone glycoside obtained from Teucrium gnaphalodes L'Her (Lamiaceae), on urolithiasis. Objective To evaluate anti-urolithiatic effects of diosmin in ammonium chloride and ethylene glycol-induced renal stone in experimental animals. Materials and methods Thirty Sprague-Dawley were divided into five groups (n=6) receiving the following treatments, respectively, p.o. for 15 consecutive days: distilled water, 0.75% v/v ethylene glycol + 2% w/v ammonium chloride, 0.75% v/v ethylene glycol + 2% w/v ammonium chloride + cystone(r) 750 mg/kg, 0.75% v/v ethylene glycol + 2% w/v ammonium chloride + diosmin 10 mg/kg or 0.75% v/v ethylene glycol + 2% w/v ammonium chloride + diosmin 20 mg/kg. Different biomarkers of urolithiasis in urine and serum were evaluated and histopathological examination of kidney was done. Results Animals treated with diosmin (both 10 and 20 mg/kg) had significantly (p < 0.005) decreased in kidney weight, urinary pH, total urinary protein, urinary calcium, phosphorus, serum potassium, sodium, magnesium, creatinine, uric acid and blood urea nitrogen levels and significantly (p < 0.005) increased in urinary volume, urinary magnesium, potassium, sodium, creatinine, uric acid and serum calcium levels in comparison to animals treated with ethylene glycol and ammonium chloride. However, results were better with diosmin 20 mg/kg in comparison to the control group. Conclusion Diosmin (10 and 20 mg/kg) has very good anti-urolithiatic activity similar to the standard drug cystone(r). PMID- 26799962 TI - Marijuana 2015: The More Things Change. PMID- 26799969 TI - Upcoming therapeutic targets in cutaneous lupus erythematous. AB - Novel insights into molecular mechanisms have altered our understanding of the pathogenesis of autoimmune skin disorders. Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease characterized by auto-aggressive skin inflammation which histologically presents with interface dermatitis. This inflammation is driven by interferon (IFN)-regulated proinflammatory cytokines that orchestrate the B- and T-cell mediated lesional inflammation. During the last years, therapeutic strategies have focused on these players: biologicals targeting type I IFNs and their receptors as well as anti-B-cell drugs have been investigated in clinical trials with variable success. Very recently, CLE gene expression analyses revealed lesional activation of several pathways of the immune system, thus providing potential new therapeutic targets. In this article, we review the current knowledge concerning pathways and key mediators involved in the pathogenesis of cutaneous lupus erythematosus (including TLR-dependent and TLR independent immune activation, NfkB, TBK1, PI3K, MAPK, JAK/STAT-pathway) and their inhibitors (e.g. chloroquine, bufalin, duvelisib, rapamycin, R788, KN-93, amlexanox, tofacitinib, ruxolitinib, baricitinib), and discuss emerging strategies for the treatment of CLE and related diseases. PMID- 26799958 TI - Occurrence of Viruses and Associated Grain Yields of Paired Symptomatic and Nonsymptomatic Tillers in Kansas Winter Wheat Fields. AB - Vector-borne virus diseases of wheat are recurrent in nature and pose significant threats to crop production worldwide. In the spring of 2011 and 2012, a state wide sampling survey of multiple commercial field sites and university-managed Kansas Agricultural Experiment Station variety performance trial locations spanning all nine crop-reporting regions of the state was conducted to determine the occurrence of Barley yellow dwarf virus-PAV (BYDV-PAV), Cereal yellow dwarf virus-RPV, Wheat streak mosaic virus (WSMV), High plains virus, Soilborne wheat mosaic virus, and Wheat spindle streak mosaic virus using enzyme-linked immunosorbent assays (ELISA). As a means of directly coupling tiller infection status with tiller grain yield, multiple pairs of symptomatic and nonsymptomatic plants were selected and individual tillers were tagged for virus species and grain yield determination at the variety performance trial locations. BYDV-PAV and WSMV were the two most prevalent species across the state, often co-occurring within location. Of those BYDV-PAV- or WSMV-positive tillers, 22% and 19%, respectively, were nonsymptomatic, a finding that underscores the importance of sampling criteria to more accurately assess virus occurrence in winter wheat fields. Symptomatic tillers that tested positive for BYDV-PAV produced significantly lower grain yields compared with ELISA-negative tillers in both seasons, as did WSMV-positive tillers in 2012. Nonsymptomatic tillers that tested positive for either of the two viruses in 2011 produced significantly lower grain yields than tillers from nonsymptomatic, ELISA-negative plants, an indication that these tillers were physiologically compromised in the absence of virus associated symptoms. Overall, the virus survey and tagged paired-tiller sampling strategy revealed effects of virus infection on grain yield of individual tillers of plants grown under field conditions and may provide a complementary approach toward future estimates of the impact of virus incidence on crop health in Kansas. PMID- 26799966 TI - Genomics of Preterm Birth--Evidence of Association and Evolving Investigations. AB - Preterm birth (PTB) is a large public health problem in the United States and worldwide. There is a clear genetic component to the pathogenesis of PTB, as evidenced by twin studies, heritability studies, and investigations from large population databases. Although numerous single nucleotide polymorphisms have been associated with PTB, results have been inconsistent and overall disappointing. With recent advances in genetic technology, investigations are moving beyond simple, more traditional candidate gene studies, and have expanded to encompass more exploratory analyses using high-throughput genetic techniques. Care should be taken to consider the potential impact of fetal genotype, the environment, and gene-drug interactions (pharmacogenomics) in addition to maternal genotype. Future research should capitalize on evolving analytic techniques, including pathway analyses and correlation of genetic and functional data to optimize discovery, increase knowledge regarding prematurity pathogenesis, and begin to develop novel therapeutic strategies. PMID- 26799965 TI - Perinatal Neuroprotection for Extremely Preterm Infants. AB - The preterm brain is vulnerable to injury through multiple mechanisms, from direct cerebral injury through ischemia and hemorrhage, indirect injury through inflammatory processes, and aberrations in growth and development. While prevention of preterm birth is the best neuroprotective strategy, this is not always possible. This article will review various obstetric and neonatal practices that have been shown to confer a neuroprotective effect on the developing brain. PMID- 26799955 TI - Earliest "Domestic" Cats in China Identified as Leopard Cat (Prionailurus bengalensis). AB - The ancestor of all modern domestic cats is the wildcat, Felis silvestris lybica, with archaeological evidence indicating it was domesticated as early as 10,000 years ago in South-West Asia. A recent study, however, claims that cat domestication also occurred in China some 5,000 years ago and involved the same wildcat ancestor (F. silvestris). The application of geometric morphometric analyses to ancient small felid bones from China dating between 5,500 to 4,900 BP, instead reveal these and other remains to be that of the leopard cat (Prionailurus bengalensis). These data clearly indicate that the origins of a human-cat 'domestic' relationship in Neolithic China began independently from South-West Asia and involved a different wild felid species altogether. The leopard cat's 'domestic' status, however, appears to have been short-lived--its apparent subsequent replacement shown by the fact that today all domestic cats in China are genetically related to F. silvestris. PMID- 26799968 TI - Effects of Consideration of Future Consequences and Temporal Framing on Acceptance of the HPV Vaccine Among Young Adults. AB - This study examines how individual difference in consideration of future consequences (CFC) and temporal framing (i.e., present- vs. future-oriented message) interact to influence the persuasive outcomes of a health message promoting human papillomavirus (HPV) vaccination among young adults. Results of an experiment (N = 416) showed a significant interaction effect of CFC and temporal framing on persuasion. The nature of the interaction suggested that individuals with high CFC generally were more persuaded by the present-oriented messages, compared to the future-oriented messages. On the other hand, those with low CFC responded similarly to the present- and future-oriented messages. Implications of the findings for HPV vaccination messaging are discussed. PMID- 26799963 TI - Reversing neuromuscular blockade: inhibitors of the acetylcholinesterase versus the encapsulating agents sugammadex and calabadion. AB - INTRODUCTION: Acetylcholinesterase inhibitors (neostigmine, edrophonium) and encapsulating agents (sugammadex and calabadion) can be used to reverse residual neuromuscular blockade (NMB). AREAS COVERED: This review provides information about efficacy, effectiveness, and side effects of drugs (acetylcholinesterase inhibitors and encapsulating agents) used to reverse neuromuscular blocking agents (NMBAs). EXPERT OPINION: The therapeutic range of acetylcholinesterase inhibitors is narrow and effectiveness studies demonstrate clinicians don't use these unspecific reversal agents effectively to increase postoperative respiratory safety. The encapsulating drugs sugammadex and calabadion reverse all levels of NMB, and complete recovery of muscle strength can be achieved almost immediately after administration. For this reason encapsulating agents can be used as a solution for "cannot intubate cannot ventilate"- situations. Poor binding selectivity of encapsulating agents carries the risk of displacement of the NMBA by a competitively binding drug, which may lead to recurarization. In order to avoid side-effects, related to unspecific binding of endogenous proteins and drugs administered perioperatively it is prudent to titrate the dose of reversal agents to the minimal effective dose, depending on the depth of neuromuscular transmission block identified by neuromuscular transmission monitoring. Calabadions provide a diversified (increased binding selectivity) and expanded (reversal of benzylisoquinolines) spectrum of possible indications. PMID- 26799973 TI - Primary FSGS in Nephrotic Adults: Clinical Profile, Response to Immunosuppression and Outcome. AB - AIM: Primary focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic proteinuria in adults. Most studies on FSGS have combined pediatric and adult patients. This study aims at assessing the response to immunosuppression and its impact on renal survival in adults with primary FSGS. METHODS: Patients with nephrotic proteinuria with primary FSGS seen from January 2010 to December 2014 were included. Clinical, laboratory and treatment details were recorded. Deterioration in renal function was defined as >=50% decline in estimated glomerular filtration rate (eGFR) or progression to end-stage renal disease. RESULTS: There were 116 patients with median follow-up of 23.6 (6-65.1) months. Baseline proteinuria was 5.1 +/- 2.6 g/day and eGFR was 96.9 +/- 35.1 ml/min/1.73 m2. One hundred one (94.4%) patients had received angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB). One hundred fourteen patients received steroids. Forty two of 114 patients (36.8%)were steroid resistant. Thirty eight received calcineurin inhibitors (CNI). Seventeen (44.7%) were CNI resistant of which 2 achieved remission with alternate immunosuppression. Eleven (9.5%) patients had worsening renal function - 9 had no remission, 2 had PR with none in CR (30 vs. 5.6% vs. 0, respectively, log-rank, p < 0.001). ACEi/ARBs use and remission of proteinuria were independently associated with better renal survival. CONCLUSION: Achieving remission, whether complete or partial, is the critical factor in predicting renal survival in nephrotic adults with primary FSGS. Steroid-resistant patients have reasonable renal survival, if proteinuria is reduced with timely use of alternate immunosuppression. CNI resistance is a major hurdle in management with limited treatment options. PMID- 26799959 TI - Involving Families with Osteogenesis Imperfecta in Health Service Research: Joint Development of the OI/ECE Questionnaire. AB - BACKGROUND: Despite the growing interest in understanding the psycho-social impact of rare genetic diseases, few studies examine this concept and even fewer seek to obtain feedback from families who have lived the experience. The aim of this project was to involve families of children living with osteogenesis imperfecta (OI) in the development of a tool to assess the impact of OI on the lives of patients and their families. METHODS: This project used an integrated knowledge translation approach in which knowledge users (clinicians and people living with OI and their families) were consulted throughout the four steps of development, that is: content mapping, item generation, tool appraisal and pre testing of the questionnaires. The International Classification of Functioning and Health was used as a framework for content mapping. Based on a scoping review we selected two validated tools to use as a basis for developing the questionnaire. The final parent self-report version measured six domains: experience of diagnosis; use of health services; use of social and psychological support services; expectations about tertiary specialized centers; and socio demographic information. RESULTS: A total of 27 out of 40 families receiving care at the Shriners Hospital for Children-Canada and invited to participate in the pre-test returned the completed questionnaires. In more than two-thirds of families (69%; n = 18) OI was suspected either at or within the first 3 months after birth. Up to 46% of families consulted between 3 and 5 doctors (46%; n = 12) prior to final diagnosis. The use of services by families varied from 0 to 16 consultations, 0 to 9 exploratory examinations and 1 to 10 types of allied health services. In the 12 months prior to the study, fewer than a quarter of children had been admitted, for treatment, for hospital stays of longer than 8 hours or to an emergency department (24% and 9% respectively). Only 29% of parents received psychological support. CONCLUSION: This joint development process generated a tool, with good psychometric properties, that provides unique insight into the experiences of patients and families with OI, the psycho-social impact of the illness, and their service needs and expectations. PMID- 26799970 TI - Whole-Body Diffusion-Weighted Imaging in Chronic Recurrent Multifocal Osteomyelitis in Children. AB - OBJECTIVE: Chronic recurrent multifocal osteomyelitis/ chronic non-bacterial osteomyelitis (CRMO/ CNO) is a rare auto-inflammatory disease and typically manifests in terms of musculoskeletal pain. Because of a high frequency of musculoskeletal disorders in children/ adolescents, it can be quite challenging to distinguish CRMO/ CNO from nonspecific musculoskeletal pain or from malignancies. The purpose of this study was to evaluate the visibility of CRMO lesions in a whole-body diffusion-weighted imaging (WB-DWI) technique and its potential clinical value to better characterize MR-visible lesions. MATERIAL AND METHODS: Whole-body imaging at 3T was performed in 16 patients (average: 13 years) with confirmed CRMO. The protocol included 2D Short Tau Inversion Recovery (STIR) imaging in coronal and axial orientation as well as diffusion-weighted imaging in axial orientation. Visibility of lesions in DWI and STIR was evaluated by two readers in consensus. The apparent diffusion coefficient (ADC) was measured for every lesion and corresponding reference locations. RESULTS: A total of 33 lesions (on average 2 per patient) visible in STIR and DWI images (b = 800 s/mm2 and ADC maps) were included, predominantly located in the long bones. With a mean value of 1283 mm2/s in lesions, the ADC was significantly higher than in corresponding reference regions (782 mm2/s). By calculating the ratio (lesion to reference), 82% of all lesions showed a relative signal increase of 10% or higher and 76% (25 lesions) showed a signal increase of more than 15%. The median relative signal increase was 69%. CONCLUSION: This study shows that WB-DWI can be reliably performed in children at 3T and predominantly, the ADC values were substantially elevated in CRMO lesions. WB-DWI in conjunction with clinical data is seen as a promising technique to distinguish benign inflammatory processes (in terms of increased ADC values) from particular malignancies. PMID- 26799957 TI - A Polymorphism in the Processing Body Component Ge-1 Controls Resistance to a Naturally Occurring Rhabdovirus in Drosophila. AB - Hosts encounter an ever-changing array of pathogens, so there is continual selection for novel ways to resist infection. A powerful way to understand how hosts evolve resistance is to identify the genes that cause variation in susceptibility to infection. Using high-resolution genetic mapping we have identified a naturally occurring polymorphism in a gene called Ge-1 that makes Drosophila melanogaster highly resistant to its natural pathogen Drosophila melanogaster sigma virus (DMelSV). By modifying the sequence of the gene in transgenic flies, we identified a 26 amino acid deletion in the serine-rich linker region of Ge-1 that is causing the resistance. Knocking down the expression of the susceptible allele leads to a decrease in viral titre in infected flies, indicating that Ge-1 is an existing restriction factor whose antiviral effects have been increased by the deletion. Ge-1 plays a central role in RNA degradation and the formation of processing bodies (P bodies). A key effector in antiviral immunity, the RNAi induced silencing complex (RISC), localises to P bodies, but we found that Ge-1-based resistance is not dependent on the small interfering RNA (siRNA) pathway. However, we found that Decapping protein 1 (DCP1) protects flies against sigma virus. This protein interacts with Ge-1 and commits mRNA for degradation by removing the 5' cap, suggesting that resistance may rely on this RNA degradation pathway. The serine-rich linker domain of Ge-1 has experienced strong selection during the evolution of Drosophila, suggesting that this gene may be under long-term selection by viruses. These findings demonstrate that studying naturally occurring polymorphisms that increase resistance to infections enables us to identify novel forms of antiviral defence, and support a pattern of major effect polymorphisms controlling resistance to viruses in Drosophila. PMID- 26799967 TI - Short- and Long-Term Outcomes for Extremely Preterm Infants. AB - Prematurity is the leading cause of infant mortality worldwide. In developed countries, extremely preterm infants contribute disproportionately to both neonatal and infant mortality. Survival of this high-risk population has incrementally improved in recent years. Despite these improvements, approximately one in four extremely preterm infants dies during the birth hospitalization. Among those who survive, respiratory and other morbidities are common, although their effect on quality of life is variable. In addition, long-term neurodevelopmental impairment is a large concern for patients, clinicians, and families. However, the interplay of multiple factors contributes to neurodevelopmental impairment, with measures that change over time and outcomes that can be difficult to define and predict. Understanding outcomes of extremely preterm infants can help better counsel families regarding antenatal and postnatal care and guide strategies to improve survival without morbidity. This review summarizes recent evidence to provide an overview into the short- and long term outcomes for extremely preterm infants. PMID- 26799971 TI - Monoclonal Antibody RYSK173 Recognizes the Dinuclear Zn Center of Serum Carnosinase 1 (CN-1): Possible Consequences of Zn Binding for CN-1 Recognition by RYSK173. AB - BACKGROUND AND AIMS: The proportion of serum carnosinase (CN-1) recognized by RYSK173 monoclonal antibody negatively correlates with CN-1 activity. We thus hypothesized that the epitope recognized by RYSK173 is accessible only in a catalytically incompetent conformation of the zinc dependent enzyme and we mapped its position in the CN-1 structure. Since patients with kidney failure are often deficient in zinc and other trace elements we also assessed the RYSK173 CN-1 proportion in serum of these patients and studied the influence of hemodialysis hereon in relation to Zn2+ and Cu2+ concentration during hemodialysis. METHODS AND RESULTS: Epitope mapping using myc-tagged CN-1 fragments and overlapping peptides revealed that the RYSK173 epitope directly contributes to the formation of the dinuclear Zn center in the catalytic domain of homodimeric CN-1. Binding of RYSK173 to CN-1 was however not influenced by addition of Zn2+ or Cu2+ to serum. In serum of healthy controls the proportion of CN-1 recognized by RYSK173 was significantly lower compared to end-stage renal disease (ESRD) patients (1.12 +/- 0.17 vs. 1.56 +/- 0.40% of total CN-1; p<0.001). During hemodialysis the relative proportion of RYSK173 CN-1 decreased in parallel with increased serum Zn2+ and Cu2+ concentrations after dialysis. CONCLUSIONS: Our study clearly indicates that RYSK173 recognizes a sequence within the transition metal binding site of CN-1, thus supporting our hypothesis that metal binding to CN-1 masks the epitope. The CN-1 RYSK173 proportion appears overall increased in ESRD patients, yet it decreases during hemodialysis possibly as a consequence of a relative increase in transition metal bound enzyme. PMID- 26799975 TI - Two-dimensional liquid chromatography (LC) of phenolic compounds from the shoots of Rubus idaeus 'Glen Ample' cultivar variety. AB - In this study the application of two-dimensional LC (2D LC) for qualitative analysis of polyphenols and simple phenols in the shoots of Rubus idaeus 'Glen Ample' variety is presented. In the preliminary analysis, the methanol extract of the shoots was analyzed by one-dimensional LC. One-dimensional LC separation profiles of phenolics from R. idaeus 'Glen Ample' shoots were dependent on column type, mobile phase composition and gradient program used. Two-dimensional LC system was built from connecting an octadecyl C-18 silica column in the first dimension and pentafluorophenyl column in the second dimension, coupled with DAD and MS (ESI, APCI, DUIS ionization) detectors. A total of 34 phenolic compounds belonging to the groups of phenolic acids, ellagitannins, flavan-3-ols, flavonols and ellagic acid conjugates were identified in the shoots of R. idaeus 'Glen Ample'. The established 2D LC method offers an effective tool for analysis of phenolics present in Rubus species. PMID- 26799974 TI - Barriers and Facilitators Associated with Non-Surgical Treatment Use for Osteoarthritis Patients in Orthopaedic Practice. AB - INTRODUCTION: International evidence-based guidelines for the management of patients with hip and knee osteoarthritis (OA) recommend to start with (a combination of) non-surgical treatments, and using surgical intervention only if a patient does not respond sufficiently to non-surgical treatment options. Despite these recommendations, there are strong indications that non-surgical treatments are not optimally used in orthopaedic practice. To improve the adoption of non-surgical treatments, more insight is needed into barriers and facilitators of these treatments. Therefore, this study assessed which barriers and facilitators are associated with the use and prescription of different non surgical treatments before hip and knee OA in orthopaedic practice among patients and orthopaedic surgeons in the Netherlands. MATERIALS AND METHODS: We performed two internet-based surveys among 172 orthopaedic surgeons and 174 OA patients. Univariate association and multivariable regression techniques are used to identify barriers and facilitators associated with the use of non-surgical treatments. RESULTS: Most barriers and facilitators among patients were associated with the use of physical therapy, lifestyle advice and dietary therapy. Among orthopaedic surgeons, most were associated with prescription of acetaminophen, dietary therapy and physical therapy. Examples of barriers and facilitators among patients included "People in my environment had positive experiences with a surgery" (facilitator for education about OA), and "Advice of people in my environment to keep on moving" (facilitator for lifestyle and dietary advice). For orthopaedic surgeons, examples were "Lack of knowledge about guideline" (barrier for lifestyle advice), "Agreements/ deliberations with primary care" and "Easy communication with a dietician" (facilitators for dietary therapy). Also the belief in the efficacy of these treatments was associated with increased prescription. CONCLUSIONS: Strategies to improve non-surgical treatment use in orthopaedic practice should be targeted at changing the beliefs of orthopedic surgeons, communication with other OA care providers and involving patient's environment in OA treatment. PMID- 26799976 TI - Quantitative and fingerprinting analysis of Pogostemon cablin based on GC-FID combined with chemometrics. AB - In this study, a simple, sensitive and reliable gas chromatography-flame ionization detection (GC-FID) method is established for quantitative chemical fingerprinting of essential oils from Pogostemon cablin. Oil samples are prepared by hydrodistillation, with yields ranging from 0.73% to 2.02%. The two main components of the oil, patchouli alcohol and pogostone, were detected simultaneously in 36 samples and were found to have average contents of 43.07% and 7.84%, respectively. The method was validated in terms of linearity, sensitivity, precision, stability, and accuracy. All calibration curves showed excellent linearity (r(2)>0.9992) within the test ranges, and the relative standard deviation (RSD) values for intra- and inter-day precision were less than 1.5%, indicating a high degree of precision. The GC-FID chemical fingerprints of the 36 samples were established using 12 common peaks which account for over 90% of the total peak area. Chemometric techniques, including similarity analysis and hierarchical cluster analysis, were also employed to explore the similarities and outstanding consistencies among different P. cablin oil samples. The results demonstrate that chromatographic fingerprinting and quantitative analysis can be achieved simultaneously when evaluating quality and authenticating samples of P. cablin. PMID- 26799977 TI - Development and application of an UHPLC-MS method for comparative pharmacokinetic study of phenolic components from dragon's blood in rats under simulated microgravity environment. AB - Dragon's blood is a commonly used Chinese herbal medicine shown to have protective effects in simulated microgravity in rats and mice. The current study aimed to develop an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS) method for simultaneous determination of four phenolic components from the herb: loureirin A, loureirin C, 7,4'-dihydroxyflavone and pterostilbene in rats, and use the method for comparative study on the pharmacokinetics (PK) and excretion of these components in rats after oral dosage of dragon's blood under simulated microgravity environments. The results showed the developed UHPLC-MS method was sensitive and rapid. The comparative pharmacokinetic study in rats showed loureirin A, loureirin C and 7,4 dihydroxyflavone had decreased Cmax and AUC and increased Vd and CL in simulated microgravity environment; but pterostilbene had the opposite changes. The four phenolic components also showed increased or decreased excretions in simulated microgravity rats. These results indicate the chemical structure and physicochemical property, as well as physiological conditions may have an impact on the absorption and excretion of phenolic components in simulated microgravity environment. It also implies that different drug may behave differently in the same spaceflight condition leading to an increase or a reduction in pharmacodynamic outcomes. PMID- 26799978 TI - Preclinical pharmacokinetics and tissue distribution of a novel multikinase inhibitor BZG by validated UPLC-MS/MS assay. AB - A simple and sensitive UPLC-MS/MS assay was developed and validated for rapid determination of BZG in rat plasma and tissues. All biological samples were prepared by protein precipitation method using Imatinib as an internal standard (IS). The analyte and IS were separated on a C18 reverse phase analytical column with 4.5 min of analytical run, at flow rate of 0.3 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) by multiple reactions monitoring (MRM) of the transitions at m/z 451.0->254.0 for BZG and m/z 494.3->394.1 for IS, respectively. The linearity of this method was found to be within the concentration range of 0.5-2500 ng/mL with a lower limit of quantification of 0.5 ng/mL. All validation parameter results were within the acceptable range described in guideline for bioanalytical method validation. The method was successfully applied to a pharmacokinetic and tissue distribution study of BZG in rats. With the preliminary knowledge of in vivo pharmacokinetics and disposition properties, this study will be beneficial for further development of BZG. PMID- 26799979 TI - Evaluation of hepatic metabolism and pharmacokinetics of ibuprofen in rats under chronic hypobaric hypoxia for targeted therapy at high altitude. AB - With studies indicative of altered drug metabolism and pharmacokinetics (DMPK) under high altitude (HA)-induced hypobaric hypoxia, consideration of better therapeutic approaches has continuously been aimed in research for HA related illness management. DMPK of drugs like ibuprofen may get affected under hypoxia which establishes the requirement of different therapeutic dose regimen to ensure safe and effective therapy at HA. This study examined the effects of the chronic hypobaric hypoxia (CHH) on hepatic DMPK of ibuprofen in rats. Experimental animals were exposed to simulated altitude of 7620 m (~25,000 ft) for CHH exposure (7 or 14 days) in decompression chamber and administered with ibuprofen (80 mg/kg, body weight, p.o.). Results demonstrated that CHH significantly altered PK variables of ibuprofen and activities of both phase-I and II hepatic metabolic enzymes as compared to the animals under normoxic conditions. Hepatic histopathological observations also revealed marked alterations. Increase in pro inflammatory cytokines/chemokines viz. IL-1beta, IL-2, IFN-gamma, TNF-alpha exhibited close relevance with diminished CYP2C9 expression under CHH. Moreover, the down-regulated CYP2C9 level further supported the underlying mechanism for reduced metabolism of ibuprofen and as a result, increased retention of parent drug in the system. Increased mean retention time, Vd, T1/2 of ibuprofen, and decreased AUC, Cmax and clearance during CHH further strengthened the present findings. In conclusion, CHH exposure significantly affects hepatic DMPK of ibuprofen, which may further influence the usual therapeutic dose-regimen. Further, there is requirement of human studies to evaluate their susceptibility toward hypobaric hypoxia. PMID- 26799981 TI - Indirect Z-Scheme BiOI/g-C3N4 Photocatalysts with Enhanced Photoreduction CO2 Activity under Visible Light Irradiation. AB - Rational design and construction of Z-scheme photocatalysts has received much attention in the field of CO2 reduction because of its great potential to solve the current energy and environmental crises. In this study, a series of Z-scheme BiOI/g-C3N4 photocatalysts are synthesized and their photocatalytic performance for CO2 reduction to produce CO, H2 and/or CH4 is evaluated under visible light irradiation (lambda > 400 nm). The results show that the as-synthesized composites exhibit more highly efficient photocatalytic activity than pure g-C3N4 and BiOI and that the product yields change remarkably depending on the reaction conditions such as irradiation light wavelength. Emphasis is placed on identifying how the charge transfers across the heterojunctions and an indirect Z scheme charge transfer mechanism is verified by detecting the intermediate I3(-) ions. The reaction mechanism is further proposed based on the detection of the intermediate (*)OH and H2O2. This work may be useful for rationally designing of new types of Z-scheme photocatalyst and provide some illuminating insights into the Z-scheme transfer mechanism. PMID- 26799982 TI - On-line two-dimensional capillary electrophoresis with mass spectrometric detection using a fully electric isolated mechanical valve. AB - CE is becoming more and more important in many fields of bioanalytical chemistry. Besides optical detection, hyphenation to ESI-MS detection is increasingly applied for sensitive identification purposes. Unfortunately, many CE techniques and methods established in research and industry are not compatible to ESI-MS since essential components of the background electrolyte interfere in ES ionization. In order to identify unknown peaks in established CE methods, here, a heart-cut 2D-CE separation system is introduced using a fully isolated mechanical valve with an internal loop of only 20 nL. In this system, the sample is separated using potentially any non-ESI compatible method in the first separation dimension. Subsequently, the portion of interest is cut by the internal sample loop of the valve and reintroduced to the second dimension where the interfering compounds are removed, followed by ESI-MS detection. When comparing the separation efficiency of the system with the valve to a system using a continuous capillary only a slight increase in peak width is observed. Ultraviolet/visible detection is integrated in the first dimension for switching time determination, enabling reproducible cutting of peaks of interest. The feasibility of the system is successfully demonstrated by a 2D analysis of a BSA tryptic digest sample using a nonvolatile (phosphate based) background electrolyte in the first dimension. PMID- 26799983 TI - Perceptual bias, more than age, impacts on eye movements during face processing. AB - Consistent with the right hemispheric dominance for face processing, a left perceptual bias (LPB) is typically demonstrated by younger adults viewing faces and a left eye movement bias has also been revealed. Hemispheric asymmetry is predicted to reduce with age and older adults have demonstrated a weaker LPB, particularly when viewing time is restricted. What is currently unclear is whether age also weakens the left eye movement bias. Additionally, a right perceptual bias (RPB) for facial judgments has less frequently been demonstrated, but whether this is accompanied by a right eye movement bias has not been investigated. To address these issues older and younger adults' eye movements and gender judgments of chimeric faces were recorded in two time conditions. Age did not significantly weaken the LPB or eye movement bias; both groups looked initially to the left side of the face and made more fixations when the gender judgment was based on the left side. A positive association was found between LPB and initial saccades in the freeview condition and with all eye movements (initial saccades, number and duration of fixations) when time was restricted. The accompanying eye movement bias revealed by LPB participants contrasted with RPB participants who demonstrated no eye movement bias in either time condition. Consequently, increased age is not clearly associated with weakened perceptual and eye movement biases. Instead an eye movement bias accompanies an LPB (particularly under restricted viewing time conditions) but not an RPB. PMID- 26799984 TI - Attenuating social affective learning effects with Memory Suppression manipulations. AB - People can form opinions of other individuals based on information about their good or bad behavior. The present study investigated whether this affective learning might depend on memory links formed between initially neutral people and valenced information. First, participants viewed neutral faces paired with sentences describing prosocial or antisocial behaviors. Second, memory suppression manipulations with the potential to aid in the forgetting of valenced information were administered. Using the Think/No think paradigm, the effectiveness of four different suppression instructions was compared: Unguided Suppression, Guided Suppression, Distraction, and Thought Substitution. Overall, all the tasks appreciably reduced affective learning based on prosocial information, but only the Guided Suppression and Thought Substitution tasks reduced affective learning based on antisocial information. These results suggest that weakening the putative memory link between initially neutral people and valenced information can decrease the effect of learned associations on the evaluation of other people. We interpreted this as indicative that social affective learning may rely on declarative memories. PMID- 26799985 TI - Palladium(II)-Catalyzed, Heteroatom-Directed, Regioselective C-H Nitration of Anilines Using Pyrimidine as a Removable Directing Group. AB - A new palladium-catalyzed, heteroatom-directed strategy for C-H nitration of anilines is described. This C-H functionalization reaction is highly ortho selective and results in very good yields. The highlight of the work is the use of pyrimidine as the removable directing group. This approach constitutes one of the rare methods of ortho-nitration of anilines, a reaction that is normally very difficult to achieve via traditional approaches. PMID- 26799987 TI - Use of a two-phase process to identify possible cases of mental ill health in the UK military. AB - Two-phase mental health screening methods, in which an abridged mental health measure is used to establish who should receive a more comprehensive assessment, may be more efficient and acceptable to respondents than a stand-alone complete questionnaire. Such two-phase methods are in use in US armed forces post deployment mental health screening. This study assesses the sensitivity and specificity of abridged instruments (used in the first phase) compared to the full instruments (the second phase), and whether false negative cases resulting from the use of abridged tests were detected by another test, among a UK military screening sample. Data from a group of UK Armed Forces personnel (n = 1464) who had completed full questionnaires assessing symptoms of post-traumatic stress disorder (PTSD) (PTSD Checklist - Civilian Version, PCL-C) and alcohol misuse (Alcohol Use Disorder Identification Test, AUDIT) were used. An abridged version of the PCL-C performed well in discriminating potential PTSD cases (as measured by the full instrument); AUDIT showed less discriminatory power, particularly due to poor specificity. Many cases missed by one abridged test would have been detected by an alternative test. Thus two-phase screening designs reduce the resource burden of a project without substantial loss of sensitivity for PTSD, but are less effective in discriminating potential cases of alcohol misuse. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26799990 TI - Comprehensive phenotypic characterization of PTLD reveals potential reliance on EBV or NF-kappaB signalling instead of B-cell receptor signalling. AB - Post-transplant lymphoproliferative disorders (PTLD) are a major problem in transplant medicine. So far, the insights into pathogenesis and potentially druggable pathways in PTLD remain scarce. We investigated a cohort of PTLD patients, consisting of both polymorphic (n = 3) and monomorphic (n = 19) B-cell lymphoproliferations. Several signalling pathways, cell of origin of PTLD and their relation to viruses were analysed by immunohistochemistry and in situ hybridization. Most PTLD were of activated B-cell origin. Two-thirds of cases showed an Epstein-Barr virus (EBV) infection of the neoplastic cells. NF-kappaB signalling components were present in the majority of cases, except for EBV infected cases with latency type III lacking CD19 and upstream B-cell signalling constituents. Proteins involved in B-cell receptor signalling like Bruton tyrosine kinase were only present in a minority of cases. Phosphoinositide 3 kinase (PI3K) was expressed in 94% of cases and the druggable PI3K class 1 catalytic subunit p110 in 76%, while proteins of other signalling transduction pathways were expressed only in single cases. Unsupervised cluster analysis revealed three distinct subgroups: (i) related to EBV infection, mainly latency type III and mostly lacking CD19, upstream B-cell signalling and NF-kappaB constituents; (ii) mostly related to EBV infection with expression of the alternative NF-kappaB pathway compound RelB, CD10, and FOXP1 or MUM1; and finally, (iii) mostly unrelated to virus infection with expression of the classic NF-kappaB pathway compound p65. EBV and NF-kappaB are important drivers in PTLD in contrast to B-cell receptor signalling. The main signal transduction pathway is related to PI3K. This links PTLD to other subgroups of EBV-related lymphomas, highlighting also new potential treatment approaches. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26799995 TI - Delivering a Positive Message. PMID- 26799992 TI - Accountability across the Continuum: The Participation of Postacute Care Providers in Accountable Care Organizations. AB - OBJECTIVE: To examine the extent to which accountable care organizations (ACOs) formally incorporate postacute care providers. DATA SOURCES: The National Survey of ACOs (N = 269, response rate 66 percent). STUDY DESIGN: We report statistics on ACOs' formal inclusion of postacute care providers and the organizational characteristics and clinical capabilities of ACOs that have postacute care. PRINCIPAL FINDINGS: Half of ACOs formally include at least one postacute service, with inclusion at higher rates in ACOs with commercial (64 percent) and Medicaid contracts (70 percent) compared to ACOs with Medicare contracts only (45 percent). ACOs that have a formal relationship with a postacute provider are more likely to have advanced transition management, end of life planning, readmission prevention, and care management capabilities. CONCLUSIONS: Many ACOs have not formally engaged postacute care, which may leave room to improve service integration and care management. PMID- 26799993 TI - Nanoscale Metal-Organic Particles with Rapid Clearance for Magnetic Resonance Imaging-Guided Photothermal Therapy. AB - Nanoscale metal-organic particles (NMOPs) are constructed from metal ions and organic bridging ligands via the self-assembly process. Herein, we fabricate NMOPs composed of Mn(2+) and a near-infrared (NIR) dye, IR825, obtaining Mn-IR825 NMOPs, which are then coated with a shell of polydopamine (PDA) and further functionalized with polyethylene glycol (PEG). While Mn(2+) in such Mn-IR825@PDA PEG NMOPs offers strong contrast in T1-weighted magnetic resonance (MR) imaging, IR825 with strong NIR optical absorbance shows efficient photothermal conversion with great photostability in the NMOP structure. Upon intravenous injection, Mn IR825@PDA-PEG shows efficient tumor homing together with rapid renal excretion behaviors, as revealed by MR imaging and confirmed by biodistribution measurement. Notably, when irradiated with an 808 nm laser, tumors on mice with Mn-IR825@PDA-PEG injection are completely eliminated without recurrence within 60 days, demonstrating the high efficacy of photothermal therapy with this agent. This study demonstrates the use of NMOPs as a potential photothermal agent, which features excellent tumor-targeted imaging and therapeutic functions, together with rapid renal excretion behavior, the latter of which would be particularly important for future clinical translation of nanomedicine. PMID- 26799988 TI - Recent Progress in the Development of HIV-1 Protease Inhibitors for the Treatment of HIV/AIDS. AB - HIV-1 protease inhibitors continue to play an important role in the treatment of HIV/AIDS, transforming this deadly ailment into a more manageable chronic infection. Over the years, intensive research has led to a variety of approved protease inhibitors for the treatment of HIV/AIDS. In this review, we outline current drug design and medicinal chemistry efforts toward the development of next-generation protease inhibitors beyond the currently approved drugs. PMID- 26799996 TI - 2015 JCO Orthodontic Practice Study, Part 3 Practice Growth and Staff Data. PMID- 26799997 TI - Long-Distance Orthodontic Treatment with Adjunctive Light Therapy. PMID- 26799998 TI - Modified Cast-Metal Haas-Type Expander for Correction of Impacted Upper First Molars in the Mixed Dentition. PMID- 26799999 TI - Targeted Mechanics for Limited Posterior Treatment with Mini-Implant Anchorage. PMID- 26800000 TI - Tunnel Traction Procedure for Deeply Impacted Canines and Resorbed Lateral Incisors. PMID- 26800001 TI - The Readers' Corner. PMID- 26800002 TI - Gold-Catalyzed Highly Selective Photoredox C(sp(2) )-H Difluoroalkylation and Perfluoroalkylation of Hydrazones. AB - The first gold-catalyzed photoredox C(sp(2) )-H difluoroalkylation and perfluoroalkylation of hydrazones with readily available RF -Br reagents is reported. The resulting gem-difluoromethylated and perfluoroalkylated hydrazones are highly functionalized, versatile molecules. A mild reduction of the coupling products can efficiently produce gem-difluoromethylated beta-amino phosphonic acids and beta-amino acid derivatives. In mechanistic studies, a difluoroalkyl radical intermediate was detected by an EPR spin-trapping experiment, indicating that a gold-catalyzed radical pathway is operating. PMID- 26800006 TI - High Numerates Count Icons and Low Numerates Process Large Areas in Pictographs: Results of an Eye-Tracking Study. AB - In two experiments, we investigated the influence of numeracy on individuals' information processing of pictographs depending on numeracy via an eye-tracker. In two conditions, participants from the general population were presented with a scenario depicting the risk of having cancer and were asked to indicate their perceived risk. The risk level was high (63%) in experiment 1 (N = 70) and low (6%) in experiment 2 (N = 69). In the default condition, participants were free to use their default strategy for information processing. In the guiding-toward the-number condition, they were prompted to count icons in the pictograph by answering with an explicit number. We used eye-tracking parameters related to the distance between sequential fixations to analyze participants' strategies for processing numerical information. In the default condition, the higher the numeracy was, the shorter the distances traversed in the pictograph were, indicating that participants counted the icons. People lower in numeracy performed increased large-area processing by comparing highlighted and nonhighlighted parts of the pictograph. In the guiding-toward-the-number condition, participants used short distances regardless of their numeracy, supporting the notion that short distances represent counting. Despite the different default processing strategies, participants processed the pictograph with a similar depth and derived similar risk perceptions. The results show that pictographs are beneficial for communicating medical risk. Pictographs make the gist salient by making the part-to-whole relationship visually available, and they facilitate low numerates' non-numeric processing of numerical information. Contemporaneously, pictographs allow high numerates to numerically process and rely on the number depicted in the pictograph. PMID- 26800003 TI - Epitope mapping and structural basis for the recognition of phosphorylated tau by the anti-tau antibody AT8. AB - Microtubule-associated protein tau becomes abnormally phosphorylated in Alzheimer's disease and other tauopathies and forms aggregates of paired helical filaments (PHF-tau). AT8 is a PHF-tau-specific monoclonal antibody that is a commonly used marker of neuropathology because of its recognition of abnormally phosphorylated tau. Previous reports described the AT8 epitope to include pS202/pT205. Our studies support and extend previous findings by also identifying pS208 as part of the binding epitope. We characterized the phosphoepitope of AT8 through both peptide binding studies and costructures with phosphopeptides. From the cocrystal structure of AT8 Fab with the diphosphorylated (pS202/pT205) peptide, it appeared that an additional phosphorylation at S208 would also be accommodated by AT8. Phosphopeptide binding studies showed that AT8 bound to the triply phosphorylated tau peptide (pS202/pT205/pS208) 30-fold stronger than to the pS202/pT205 peptide, supporting the role of pS208 in AT8 recognition. We also show that the binding kinetics of the triply phosphorylated peptide pS202/pT205/pS208 was remarkably similar to that of PHF-tau. The costructure of AT8 Fab with a pS202/pT205/pS208 peptide shows that the interaction interface involves all six CDRs and tau residues 202-209. All three phosphorylation sites are recognized by AT8, with pT205 acting as the anchor. Crystallization of the Fab/peptide complex under acidic conditions shows that CDR-L2 is prone to unfolding and precludes peptide binding, and may suggest a general instability in the antibody. PMID- 26800007 TI - Effect of malonaldehyde cross-linking on the ability of shrimp tropomyosin to elicit the release of inflammatory mediators and cytokines from activated RBL-2H3 cells. AB - BACKGROUND: Malonaldehyde, the primary by-product of lipid peroxidation in food, modifies the structural and functional properties of proteins by cross-linking. The aim of this study was to investigate the effect of malonaldehyde on the allergenicity of shrimp tropomyosin. RESULTS: RBL-2H3 cells, a model of type I allergic reactions, were sensitised with sera from patients allergic to shrimp, and were stimulated with native and cross-linked tropomyosin. Release of inflammatory mediators such as beta-hexosaminidase, histamine, tryptase, cysteinyl leukotriene, and prostaglandin D2 was clearly suppressed in a manner that depended on the extent of tropomyosin cross-linking. Release of interleukin 4 (IL-4) and IL-13 was similarly decreased. Notably, cells sensitised with one patient's serum released IL-4 at comparable levels in response to native and cross-linked tropomyosin. CONCLUSION: Cross-linking strongly modulates the ability of shrimp tropomyosin to induce release of inflammatory cytokines and mediators from activated RBL-2H3 cells. (c) 2016 Society of Chemical Industry. PMID- 26800008 TI - Prognostic impact of persistent cytogenetic abnormalities at complete remission in adult patients with acute lymphoblastic leukemia. AB - In acute myelogenous leukemia, the persistent detection of abnormal cytogenetics at complete remission (ACCR) is associated with inferior outcomes. However, the prognostic significance of ACCR in adult patients with acute lymphoblastic leukemia (ALL) is unknown. We evaluated 272 adult patients with ALL and abnormal cytogenetics at baseline who were treated with frontline induction chemotherapy, achieved complete remission (CR) and had cytogenetic analysis performed at the time of CR. ACCR was observed in 26 patients (9.6%). Median relapse-free survival was 22 months (95% CI, 12 months to not reached) for patients with ACCR vs. 48 months (range, 30-125 months) in patients with normal cytogenetics at CR (NCCR; P = 0.31). Median overall survival also did not differ significantly between the ACCR (99 months [range, 17 months to not reached]) and NCCR groups (67 months [range, 47 months to not reached], P = 0.86). The specificity of ACCR for minimal residual disease (MRD) positivity by multi-parameter flow cytometry (MFC) was 43%, and there was overall poor correlation between these two methods for the detection of residual disease. When patients were stratified by MRD status, the presence or absence of persistent cytogenetic abnormalities at CR did not add additional prognostic information. This study suggests that there is poor association between MRD assessment by MFC and the presence or absence of cytogenetic abnormalities at CR in adult patients with ALL. ACCR was not associated with adverse outcomes in ALL and did not add additional prognostic information when MRD status by MFC was known. PMID- 26800009 TI - Global gray-level thresholding based on object size. AB - In this article, we propose a fast and robust global gray-level thresholding method based on object size, where the selection of threshold level is based on recall and maximum precision with regard to objects within a given size interval. The method relies on the component tree representation, which can be computed in quasi-linear time. Feature-based segmentation is especially suitable for biomedical microscopy applications where objects often vary in number, but have limited variation in size. We show that for real images of cell nuclei and synthetic data sets mimicking fluorescent spots the proposed method is more robust than all standard global thresholding methods available for microscopy applications in ImageJ and CellProfiler. The proposed method, provided as ImageJ and CellProfiler plugins, is simple to use and the only required input is an interval of the expected object sizes. (c) 2016 International Society for Advancement of Cytometry. PMID- 26800010 TI - Impact of Freezing Time on Dornic Acidity in Three Types of Milk: Raw Donor Milk, Mother's Own Milk, and Pasteurized Donor Milk. AB - OBJECTIVE: Although under certain circumstances it is necessary to express milk, there are not many recommendations about the ideal storage conditions for human milk. The objectives of this study were to analyze the effects on Dornic acidity of frozen storage at -20 degrees C in three types of milk: raw donor milk, mother's own raw milk, and pasteurized donor milk. METHODS: Forty-three samples of raw donor milk, 40 samples of pasteurized donor milk, and 16 samples of mother's own milk were analyzed. Dornic acidity was measured at time 0, before freezing. The remaining aliquots were frozen and analyzed after 1, 2, 3, and 4 weeks and after 2 and 3 months. RESULTS: In raw donor milk, the median acidity at the start was 3 degrees D (interquartile range [IQR] 2-3 degrees D); after 3 months, it was 5 degrees D (IQR 3-7 degrees D), with a significant increase in acidity after the second week. In mother's own milk, the mean acidity at the start was 3 degrees D (IQR 2-4 degrees D) and 7 degrees D (IQR 4-8 degrees D) at 3 months. The increase was significant after the third week. In pasteurized donor milk, the mean acidity was 3 degrees D (IQR 2-3 degrees D) at the start and 2 degrees D (IQR 2-3 degrees D) at the end. When comparing the three types of milk, there were significant differences from the first week between the two types of raw milk and the pasteurized milk (p < 0.01), but not between the two raw milks (p = 0.77). CONCLUSIONS: Dornic acidity in unpasteurized milk significantly increases with the duration of freezing, probably due to the action of lipases, which is lost with pasteurization. It would be advisable to reduce the length of freezing time for unpasteurized milk. PMID- 26800011 TI - Conformational studies on peptides having dipropylglycine (Dpg) or 1 aminocycloheptanecarboxylic acid (Ac7 c) within the sequence of l-leucine (Leu) residues. AB - A conformational analysis of peptides having dipropylglycine (Dpg) or 1 aminocycloheptanecarboxylic acid (Ac7 c) within l-leucine (Leu) residues was conducted in solution and in a crystal state. Dpg and Ac7 c had similar structures with acyclic and cyclic side chains, respectively. FTIR, 1 H NMR, and CD spectra measurements revealed that the preferred conformations of Dpg- and Ac7 c-containing l-Leu peptides in solution were similar; both had a right-handed (P) 310 -helix. The Dpg-containing octapeptide adopted a right-handed (P) alpha-helix in the crystal state. Dpg and Ac7 c homopeptides had planar and helical structures as their preferred conformations, respectively; however, Dpg- and Ac7 c-containing l-Leu peptides adopted similar structures in solution. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 210-218, 2016. PMID- 26800012 TI - Using a Delphi process to determine optimal care for patients with pancreatic cancer. AB - AIM: Overall 5-year survival for pancreatic cancer is ~5%. Optimizing the care that pancreatic cancer patients receive may be one way of improving outcomes. The objective of this study was to establish components of care which Australian health professionals believe important to optimally manage patients with pancreatic cancer. METHODS: Using a Delphi process, a multidisciplinary panel of 250 health professionals were invited to provide a list of factors they considered important for optimal care of pancreatic cancer patients. They were then asked to score and then rescore (from one [no importance/disagree] to 10 [very important/agree]) the factors. The mean and coefficient of variation scores were calculated and categorized into three levels of importance. RESULTS: Overall, 63 (66% of those sent the final questionnaire; 25% of those initially invited) health professionals from nine disciplines completed the final scoring of 55 statements/factors encompassing themes of presentation/staging, surgery and biliary obstruction, multidisciplinary team details and oncology. Mean scores ranged from 3.7 to 9.7 with the highest related to communication and patient assessment. There was substantial intra- and interdisciplinary variation in views about MDT membership and roles. CONCLUSION: Overall, the opinions of Australian health professionals reflect international guideline recommended care; however, they identified a number of additional factors focusing on where patients should be treated, the importance of clear communication and the need for multidisciplinary care which were not included in current clinical practice guidelines. Differences in priorities between specialty groups were also identified. PMID- 26800013 TI - Finding a moral compass . . . without a compass: Evolution and ethics. PMID- 26800015 TI - The enduring puzzle of the human chin. AB - Although modern humans are considered to be morphologically distinct from other living primates because of our large brains, dexterous hands, and bipedal gait, all of these features are found among extinct hominins. The chin, however, appears to be a uniquely modern human trait. Probably because of the chin's exclusivity, many evolutionary scenarios have been proposed to explain its origins. To date, researchers have developed adaptive hypotheses relating chins to speech, mastication, and sexual selection; still others see it as a structural artifact tangentially related to complex processes involving evolutionary retraction of the midfacial skeleton. Consensus has remained elusive, partly because hypotheses purporting to explain how this feature developed uniquely in modern humans are all fraught with theoretical and/or empirical shortcomings. Here we review a century's worth of chin hypotheses and discuss future research avenues that may provide greater insight into this human peculiarity. PMID- 26800014 TI - The Acheulean handaxe: More like a bird's song than a beatles' tune? AB - The goal of this paper is to provoke debate about the nature of an iconic artifact-the Acheulean handaxe. Specifically, we want to initiate a conversation about whether or not they are cultural objects. The vast majority of archeologists assume that the behaviors involved in the production of handaxes were acquired by social learning and that handaxes are therefore cultural. We will argue that this assumption is not warranted on the basis of the available evidence and that an alternative hypothesis should be given serious consideration. This alternative hypothesis is that the form of Acheulean handaxes was at least partly under genetic control. PMID- 26800017 TI - Reporting methods for processing and analysis of data from serial block face scanning electron microscopy. AB - Serial block face scanning electron microscopy is rapidly becoming a popular tool for collecting large three-dimensional data sets of cells and tissues, filling the resolution and volume gap between fluorescence microscopy and high-resolution electron microscopy. The automated collection of data within the instrument occupies the smallest proportion of the time required to prepare and analyse biological samples. It is the processing of data once it has been collected that proves the greatest challenge. In this review we discuss different methods that are used to process data. We suggest potential workflows that can be used to facilitate the transfer of raw image stacks into quantifiable data as well as propose a set of criteria for reporting methods for data analysis to enable replication of work. PMID- 26800019 TI - Porous Organic Cage Thin Films and Molecular-Sieving Membranes. AB - Porous organic cage molecules are fabricated into thin films and molecular sieving membranes. Cage molecules are solution cast on various substrates to form amorphous thin films, with the structures tuned by tailoring the cage chemistry and processing conditions. For the first time, uniform and pinhole-free microporous cage thin films are formed and demonstrated as molecular-sieving membranes for selective gas separation. PMID- 26800020 TI - Influence of Solvation and Dynamics on the Mechanism and Kinetics of Nucleophilic Aromatic Substitution Reactions in Liquid Ammonia. AB - The role of the solvent and the influence of dynamics on the kinetics and mechanism of the SNAr reaction of several halonitrobenzenes in liquid ammonia, using both static calculations and dynamic ab initio molecular dynamics simulations, are investigated. A combination of metadynamics and committor analysis methods reveals how this reaction can change from a concerted, one-step mechanism in gas phase to a stepwise pathway, involving a metastable Meisenheimer complex, in liquid ammonia. This clearly establishes, among others, the important role of the solvent and highlights the fact that accurately treating solvation is of crucial importance to correctly unravel the reaction mechanism. It is indeed shown that H-bond formation of the reacting NH3 with the solvent drastically reduces the barrier of NH3 addition. The halide elimination step, however, is greatly facilitated by proton transfer from the reacting NH3 to the solvent. Furthermore, the free energy surface strongly depends on the halide substituent and the number of electron-withdrawing nitro substituents. PMID- 26800021 TI - Insertion of Vertically Aligned Nanowires into Living Cells by Inkjet Printing of Cells. AB - Effective insertion of vertically aligned nanowires (NWs) into cells is critical for bioelectrical and biochemical devices, biological delivery systems, and photosynthetic bioenergy harvesting. However, accurate insertion of NWs into living cells using scalable processes has not yet been achieved. Here, NWs are inserted into living Chlamydomonas reinhardtii cells (Chlamy cells) via inkjet printing of the Chlamy cells, representing a low-cost and large-scale method for inserting NWs into living cells. Jetting conditions and printable bioink composed of living Chlamy cells are optimized to achieve stable jetting and precise ink deposition of bioink for indentation of NWs into Chlamy cells. Fluorescence confocal microscopy is used to verify the viability of Chlamy cells after inkjet printing. Simple mechanical considerations of the cell membrane and droplet kinetics are developed to control the jetting force to allow penetration of the NWs into cells. The results suggest that inkjet printing is an effective, controllable tool for stable insertion of NWs into cells with economic and scale related advantages. PMID- 26800022 TI - Multicentered epidemiological study of factors associated with total bacterial count in the saliva of older people requiring nursing care. AB - AIM: To clarify whether the number of present teeth, independent of other well known factors, was associated with the total bacterial count in the saliva of older people requiring care at nursing homes in a multicentered epidemiological survey. METHOD: The participants were 618 older people (mean age 86.8 +/- 6.9 years; 122 men, 496 women) residing in 14 nursing homes across Japan. The dependent variable was the participant's salivary bacterial count, and the independent variables were basic demographic data, oral conditions and activity of daily living (measured by Barthel Index). Statistical analysis was first carried out by Student's t-test, Pearson's correlation coefficient analysis and Spearman's rank correlation coefficient analysis. Independent variables found to have a significant relationship to their salivary bacterial count by the univariate analyses were further examined by stepwise multivariate analysis. RESULTS: The independent variables shown by univariate analysis to have a significant positive relationship with higher salivary bacterial count were presence of food residue (P = 0.001), absence of mouth dryness (P = 0.001), need of oral care assistance (P = 0.001), inability to keep the mouth opened (P = 0.009), inability to gargle (P = 0.002), denture use (P = 0.004), higher number of present teeth (P = 0.006) and lower Barthel Index (P = 0.001). Subsequent multivariate analysis identified presence of food residue (P = 0.031), higher number of present teeth (P = 0.043) and lower Barthel Index (P = 0.001) as independent associated factors for higher salivary bacterial count. CONCLUSIONS: The present study found that presence of food residue, higher number of present teeth and decreased activity of daily living were significantly related to higher bacterial count in the saliva of older people requiring care. Geriatr Gerontol Int 2017; 17: 219-225. PMID- 26800023 TI - Inclusion of Yucca schidigera extract in diets with different protein levels for dogs. AB - This study evaluated the effects of inclusion of Yucca schidigera extract (YSE) in two diets with different levels of crude protein (CP) for dogs on facal odour, nutrient digestibility, ammonia concentration in feces and hematological and serum biochemical profiles. Twenty adults Beagles were used, distributed in a randomized block design in a 2 * 4 factorial design (two diets, 25% and 34% CP, and four YSE levels: 0, 250, 500 and 750 mg/kg) with five replicates, obtained during two experimental periods. The fecal odour reduced (P < 0.05) when 500 mg/kg of YSE was used in diets with higher CP. The inclusion of YSE reduced (P < 0.05) fecal ammonia, and the inclusion of 250 and 500 mg/kg YSE reduced intestinal gas. The inclusion of 750 mg/kg YSE increased the mean corpuscular hemoglobin (MCH), alanine aminotransferase (ALT) activity and tended to increase the serum cholesterol concentration, regardless of the protein level of the diets. There was no effect on the digestibility of nutrients, fecal consistency, nitrogen balance and thickness of the intestinal wall. The inclusion of 500 mg/kg YSE is effective in reducing fecal odour in dogs receiving diets with 34% of CP. Regardless of the protein content, YSE reduces fecal ammonia, but may cause adverse effects if included at higher doses. PMID- 26800025 TI - Large-Scale Analysis of Zipf's Law in English Texts. AB - Despite being a paradigm of quantitative linguistics, Zipf's law for words suffers from three main problems: its formulation is ambiguous, its validity has not been tested rigorously from a statistical point of view, and it has not been confronted to a representatively large number of texts. So, we can summarize the current support of Zipf's law in texts as anecdotic. We try to solve these issues by studying three different versions of Zipf's law and fitting them to all available English texts in the Project Gutenberg database (consisting of more than 30 000 texts). To do so we use state-of-the art tools in fitting and goodness-of-fit tests, carefully tailored to the peculiarities of text statistics. Remarkably, one of the three versions of Zipf's law, consisting of a pure power-law form in the complementary cumulative distribution function of word frequencies, is able to fit more than 40% of the texts in the database (at the 0.05 significance level), for the whole domain of frequencies (from 1 to the maximum value), and with only one free parameter (the exponent). PMID- 26800027 TI - Recognizing Words and Reading Sentences with Microsecond Flash Displays. AB - Strings of dots can be used to construct easily identifiable letters, and these in turn can be used to write words and sentences. Prior work found that respondents could identify individual letters when all the dots were simultaneously flashed for an ultra-brief duration. Four of the experiments reported here constructed five-letter words with these dot-letters and a fifth experiment used them to write complete sentences. Respondents were able to recognize individual words that were displayed with a single, simultaneous ultra brief flash of all the letters. Further, sentences could be efficiently read with a sequence of simultaneous flashes at a frequency that produced perceptual fusion. One experiment determined the frequency range that would produce flicker fusion. Two experiments established the relation of intensity to probability of recognition with single flashes and with fused-flicker frequencies. Another established the intensities at which flicker-fused and steady displays were judged to be equal in brightness. The final experiment used those flicker-fused and steady intensities to display sentences. The two display conditions were read with equal efficiency, even though the flicker-fused displays provided light stimulation only 0.003% of the time. PMID- 26800028 TI - Leaf-morphology-assisted selection for resistance to two-spotted spider mite Tetranychus urticae Koch (Acari: Tetranychidae) in carnations (Dianthus caryophyllus L). AB - BACKGROUND: The development of a cultivar resistant to the two-spotted spider mite has provided both ecological and economic benefits to the production of cut flowers. This study aimed to clarify the mechanism of resistance to mites using an inbred population of carnations. RESULTS: In the resistant and susceptible plants selected from an inbred population, a difference was recognised in the thickness of the abaxial palisade tissue by microscopic examination of the damaged leaf. Therefore, it was assumed that mites displayed feeding preferences within the internal leaf structure of the carnation leaf. The suitability of the host plant for mites was investigated using several cultivars selected using an index of the thickness from the abaxial leaf surface to the spongy tissue. The results suggested that the cultivar associated with a thicker abaxial tissue lowered the intrinsic rate of natural increase of the mites. The cultivars with a thicker abaxial tissue of over 120 um showed slight damage in the field test. CONCLUSION: The ability of mites to feed on the spongy tissue during an early life stage from hatching to adult emergence was critical. It was possible to select a cultivar that is resistant to mites under a real cultivation environment by observing the internal structure of the leaf. (c) 2016 Society of Chemical Industry. PMID- 26800030 TI - The cytopathology of mycobacterial infection. AB - Mycobacterial infection, tuberculosis (TB) in particular, remains one of the world's deadliest communicable diseases in adults and particularly in children, in low and middle income countries. The combination of human immunodeficiency virus (HIV) and TB is often lethal with TB accounting for 25% of deaths in the HIV population. One of the cornerstones for reducing the TB epidemic is early case detection using high quality diagnostic techniques. Cytology, especially fine needle aspiration biopsy (FNAB) is able to diagnose mycobacterial infection in a rapid and cost-effective manner without requiring surgery, thus allowing appropriate management to be quickly instituted. Confirmatory ancillary tests can effectively be performed on cytologic material. In this review, the pertinent cytomorphology of mycobacterial infection in various exfoliative and FNAB specimens is presented, in both immunocompetent and immunosuppressed patients. In the immunosuppressed, the typical cytomorphology of caseating granulomatous inflammation may not be seen but suppurative necrotic inflammation, mycobacterial spindle pseudotumour or a specimen comprised entirely of necrosis may be seen instead. This review includes discussion of currently available ancillary tests that can be performed on cytologic specimens. PMID- 26800029 TI - Comparative Cost-Effectiveness of Drugs in Early versus Late Stages of Cancer; Review of the Literature and a Case Study in Breast Cancer. AB - BACKGROUND: Many oncological drugs that are being used in the adjuvant setting were first submitted for reimbursement in the metastatic stage, with differences in incremental cost-effectiveness ratios (ICERs) in both settings having potential implications for reimbursement and pricing. The aim of this study is to identify a possible trend in the cost-effectiveness for the early/adjuvant and late/metastatic stages of oncological drugs through review and case study. METHODS: We reviewed pairs of cost-effectiveness analyses of the same oncological drug in different stages for Scotland and the Netherlands. The case study in this report was directed at trastuzumab in the Dutch situation. Using a simplified Markov model, the cost-effectiveness in early and late stage of breast cancer was calculated and compared to the findings from the review. RESULTS: Comparable studies were found for cetuximab, bortezomib and bosutinib. Treatments in the late stage were found to be more expensive per QALY by a factor ranging from 1.5 to 12. The case study provided a similar result; late stage treatment was more expensive by a factor 10. Using, for example, a threshold of ? 80,000/QALY, the early stage of cetuximab, bosutinib and trastuzumab are deemed cost-effective, while their compared late stage is lifted over the threshold and potentially considered not cost-effective. CONCLUSION: ICERs of oncological drugs used in different stages are more unfavourable in the late stage than in the early stage. Applying a reasonable threshold may result in early stage treatment being deemed cost-effective while late stage potentially not. Authorities should be aware of this when assessing oncological drugs and interpreting the corresponding ICERs, in the situation where oncological drugs are generally most submitted for reimbursement in the late stage initially. PMID- 26800031 TI - The Chiropteran Brain Database: Volumetric Survey of the Hypophysis in 165 Species. AB - For nearly two decades, a database of brain structures from a large sample (272 species) of chiropterans has been widely accessible and used for socioecological analyses of mammals. However, this database remains incomplete since the hypophysis has not been measured. Since this glandular/neural structure has reproductive significance to chiropterans as for other mammals, this investigation was carried out using serial coronal sections of bat brains comprising the Heinz Stephan collection, Dusseldorf, Germany. Complete serially sectioned brains were examined in 313 individuals (165 species, 15 families). Using a well-documented method, hypophyseal volumes were determined from every fourth or sixth section in each individual. The strongest correlation was between body weight and the hypophysis (R(2) = 0.887) and its various components as well as between body weight and adenohypophysis (R(2) = 0.830) and neurohypophysis (R(2) = 0.925). Correlations were also strong for brain weight-adenohypophysis (R(2) = 0.817) and brain weight- neurohypophysis (R(2) = 0.911). Results indicated that: (1) in regression analyses, hipposiderids stand apart as having relatively large adenohypophysis; (2) analysis of residuals generated using least squares regression of hypophyseal components suggests a trend among microchiropterans where females have a relatively larger adenohypophysis than males. However, this difference is only statistically significant in the largest samples: Phyllostomidae and Vespertilionidae. Pteropodids do not appear to follow this trend. Our findings suggest both phylogenetic and sexual differences in the adenohypophysis in particular, and indicate the need for investigation of larger samples by species, especially those best understood in reproductive and social biology. PMID- 26800033 TI - Functional Atlas of the Human Fascial System. PMID- 26800032 TI - The influence of iron deficiency on the functioning of skeletal muscles: experimental evidence and clinical implications. AB - Skeletal and respiratory myopathy not only constitutes an important pathophysiological feature of heart failure and chronic obstructive pulmonary disease, but also contributes to debilitating symptomatology and predicts worse outcomes in these patients. Accumulated evidence from laboratory experiments, animal models, and interventional studies in sports medicine suggests that undisturbed systemic iron homeostasis significantly contributes to the effective functioning of skeletal muscles. In this review, we discuss the role of iron status for the functioning of skeletal muscle tissue, and highlight iron deficiency as an emerging therapeutic target in chronic diseases accompanied by a marked muscle dysfunction. PMID- 26800034 TI - Accurately determining patients who underwent robot-assisted surgery: limitations of administrative databases. PMID- 26800035 TI - Photoprotection Mechanism of Light-Harvesting Antenna Complex from Purple Bacteria. AB - Photosynthetic light-harvesting apparatus efficiently capture sunlight and transfer the energy to reaction centers, while they safely dissipate excess energy to surrounding environments for a protection of their organisms. In this study, we performed pump-probe spectroscopic measurements with a temporal window ranging from femtosecond to submillisecond on the purple bacterial antenna complex LH2 from Rhodobacter sphaeroides 2.4.1 to clarify its photoprotection functions. The observed excited state dynamics in the time range from subnanosecond to microsecond exhibits that the triplet-triplet excitation energy transfer from bacteriochlorophyll a to carotenoid takes place with a time constant of 16.7 ns. Furthermore, ultrafast spectroscopic data suggests that a molecular assembly of bacteriochlorophyll a in LH2 efficiently suppresses a generation of triple bacteriochlorophyll a. PMID- 26800036 TI - Editorial 2016. PMID- 26800037 TI - Recipient of the 2015 Molecular Ecology Prize: Fred Allendorf. PMID- 26800038 TI - Population genomic footprints of fine-scale differentiation between habitats in Mediterranean blue tits. AB - Linking population genetic variation to the spatial heterogeneity of the environment is of fundamental interest to evolutionary biology and ecology, in particular when phenotypic differences between populations are observed at biologically small spatial scales. Here, we applied restriction-site associated DNA sequencing (RAD-Seq) to test whether phenotypically differentiated populations of wild blue tits (Cyanistes caeruleus) breeding in a highly heterogeneous environment exhibit genetic structure related to habitat type. Using 12 106 SNPs in 197 individuals from deciduous and evergreen oak woodlands, we applied complementary population genomic analyses, which revealed that genetic variation is influenced by both geographical distance and habitat type. A fine scale genetic differentiation supported by genome- and transcriptome-wide analyses was found within Corsica, between two adjacent habitats where blue tits exhibit marked differences in breeding time while nesting < 6 km apart. Using redundancy analysis (RDA), we show that genomic variation remains associated with habitat type when controlling for spatial and temporal effects. Finally, our results suggest that the observed patterns of genomic differentiation were not driven by a small proportion of highly differentiated loci, but rather emerged through a process such as habitat choice, which reduces gene flow between habitats across the entire genome. The pattern of genomic isolation-by environment closely matches differentiation observed at the phenotypic level, thereby offering significant potential for future inference of phenotype-genotype associations in a heterogeneous environment. PMID- 26800039 TI - Genome Sequences of Populus tremula Chloroplast and Mitochondrion: Implications for Holistic Poplar Breeding. AB - Complete Populus genome sequences are available for the nucleus (P. trichocarpa; section Tacamahaca) and for chloroplasts (seven species), but not for mitochondria. Here, we provide the complete genome sequences of the chloroplast and the mitochondrion for the clones P. tremula W52 and P. tremula x P. alba 717 1B4 (section Populus). The organization of the chloroplast genomes of both Populus clones is described. A phylogenetic tree constructed from all available complete chloroplast DNA sequences of Populus was not congruent with the assignment of the related species to different Populus sections. In total, 3,024 variable nucleotide positions were identified among all compared Populus chloroplast DNA sequences. The 5-prime part of the LSC from trnH to atpA showed the highest frequency of variations. The variable positions included 163 positions with SNPs allowing for differentiating the two clones with P. tremula chloroplast genomes (W52, 717-1B4) from the other seven Populus individuals. These potential P. tremula-specific SNPs were displayed as a whole-plastome barcode on the P. tremula W52 chloroplast DNA sequence. Three of these SNPs and one InDel in the trnH-psbA linker were successfully validated by Sanger sequencing in an extended set of Populus individuals. The complete mitochondrial genome sequence of P. tremula is the first in the family of Salicaceae. The mitochondrial genomes of the two clones are 783,442 bp (W52) and 783,513 bp (717 1B4) in size, structurally very similar and organized as single circles. DNA sequence regions with high similarity to the W52 chloroplast sequence account for about 2% of the W52 mitochondrial genome. The mean SNP frequency was found to be nearly six fold higher in the chloroplast than in the mitochondrial genome when comparing 717-1B4 with W52. The availability of the genomic information of all three DNA-containing cell organelles will allow a holistic approach in poplar molecular breeding in the future. PMID- 26800044 TI - Training experts in family medicine teaching. AB - Family medicine teachers require specific educational skills. A framework for their professional development is essential for future development of the discipline in Europe. EURACT developed a framework on educational expertise, and subsequently applied it in a curriculum of teaching-skills courses of various levels. The aim of this article is to describe the development of the teaching framework, and of an international three-level course programme for 'teaching-the teachers'. Furthermore, we describe our experiences and lessons learned, in particular with regard to the level-three programme for proficient teachers, which was new. We conclude that it is possible to develop a theoretical framework of family medicine teaching expertise and to apply it in an international high level educational programme for future experts in family medicine education. Research evidence of the usefulness of this approach is needed, and the threats for its further development into a sustainable activity are its high teacher/student ratio associated with relatively high costs and difficulties in recruiting suitable participants. PMID- 26800040 TI - Enantioselective C-H Olefination of alpha-Hydroxy and alpha-Amino Phenylacetic Acids by Kinetic Resolution. AB - Significant progress has been made in the past decade regarding the development of enantioselective C-H activation reactions by desymmetrization. However, the requirement for the presence of two chemically identical prochiral C-H bonds represents an inherent limitation in scope. Reported is the first example of kinetic resolution by a palladium(II)-catalyzed enantioselective C-H activation and C-C bond formation, thus significantly expanding the scope of enantioselective C-H activation reactions. PMID- 26800047 TI - The structures and properties of proton- and alkali-bound cysteine dimers. AB - The proton-, lithium-, and sodium-bound cysteine dimers have been investigated in a joint computational and experimental infrared multiple photon dissociation (IRMPD) study. IRMPD spectra in the 1000-2000 cm(-1) region show that protonation is localized on an amine group, and that intermolecular hydrogen bonding occurs between the protonated amine and the carbonyl oxygen of the neutral Cys moiety. Alkali-bound dimers adopt structures reminiscent of those observed for the monomeric Cys.Li(+) and Cys.Na(+) species. Calculations of the heavier Cys2.M(+) (M = K, Rb or Cs) species suggest that these are significantly less strongly bound than the lighter (M = H, Li, or Na) dimers. PMID- 26800048 TI - Identification of Putative Biomarkers for the Early Stage of Porcine Spermatogonial Stem Cells Using Next-Generation Sequencing. AB - To identify putative biomarkers of porcine spermatogonial stem cells (pSSCs), total RNA sequencing (RNA-seq) analysis was performed on 5- and 180-day-old porcine testes and on pSSC colonies that were established under low temperature culture conditions as reported previously. In total, 10,184 genes were selected using Cufflink software, followed by a logarithm and quantile normalization of the pairwise scatter plot. The correlation rates of pSSCs compared to 5- and 180 day-old testes were 0.869 and 0.529, respectively and that between 5- and 180-day old testes was 0.580. Hierarchical clustering data revealed that gene expression patterns of pSSCs were similar to 5-day-old testis. By applying a differential expression filter of four fold or greater, 607 genes were identified between pSSCs and 5-day-old testis, and 2118 genes were identified between the 5- and 180 day-old testes. Among these differentially expressed genes, 293 genes were upregulated and 314 genes were downregulated in the 5-day-old testis compared to pSSCs, and 1106 genes were upregulated and 1012 genes were downregulated in the 180-day-old testis compared to the 5-day-old testis. The following genes upregulated in pSSCs compared to 5-day-old testes were selected for additional analysis: matrix metallopeptidase 9 (MMP9), matrix metallopeptidase 1 (MMP1), glutathione peroxidase 1 (GPX1), chemokine receptor 1 (CCR1), insulin-like growth factor binding protein 3 (IGFBP3), CD14, CD209, and Kruppel-like factor 9 (KLF9). Expression levels of these genes were evaluated in pSSCs and in 5- and 180-day old porcine testes. In addition, immunohistochemistry analysis confirmed their germ cell-specific expression in 5- and 180-day-old testes. These finding may not only be useful in facilitating the enrichment and sorting of porcine spermatogonia, but may also be useful in the study of the early stages of spermatogenic meiosis. PMID- 26800049 TI - A Viral microRNA Cluster Regulates the Expression of PTEN, p27 and of a bcl-2 Homolog. AB - The Epstein-Barr virus (EBV) infects and transforms B-lymphocytes with high efficiency. This process requires expression of the viral latent proteins and of the 3 miR-BHRF1 microRNAs. Here we show that B-cells infected by a virus that lacks these non-coding RNAs (Delta123) grew more slowly between day 5 and day 20, relative to wild type controls. This effect could be ascribed to a reduced S phase entry combined with a moderately increased apoptosis rate. Whilst the first phenotypic trait was consistent with an enhanced PTEN expression in B-cells infected with Delta123, the second could be explained by very low BHRF1 protein and RNA levels in the same cells. Indeed, B-cells infected either by a recombinant virus that lacks the BHRF1 protein, a viral bcl-2 homolog, or by Delta123 underwent a similar degree of apoptosis, whereas knockouts of both BHRF1 microRNAs and protein proved transformation-incompetent. We find that that the miR-BHRF1-3 seed regions, and to a lesser extent those of miR-BHRF1-2 mediate these stimulatory effects. After this critical period, B-cells infected with the Delta123 mutant recovered a normal growth rate and became more resistant to provoked apoptosis. This resulted from an enhanced BHRF1 protein expression relative to cells infected with wild type viruses and correlated with decreased p27 expression, two pro-oncogenic events. The upregulation of BHRF1 can be explained by the observation that large BHRF1 mRNAs are the source of BHRF1 protein but are destroyed following BHRF1 microRNA processing, in particular of miR-BHRF1-2. The BHRF1 microRNAs are unlikely to directly target p27 but their absence may facilitate the selection of B-cells that express low levels of this protein. Thus, the BHRF1 microRNAs allowed a time-restricted expression of the BHRF1 protein to innocuously expand the virus B-cell reservoir during the first weeks post-infection without increasing long-term immune pressure. PMID- 26800050 TI - Exploring Butane Hash Oil Use: A Research Note. AB - The practice of "dabbing" has seen an apparent upswing in popularity in recent months within American drug subcultures. "Dabbing" refers to the use of butane extracted marijuana products that offer users much higher tetrahydrocannabinol content than flower cannabis through a single dosage process. Though considerably more potent than most marijuana strains in their traditional form, these butane hash oil products and the practice of dabbing are underexplored in the empirical literature, especially in prohibition states. A mixed-methods evaluation of a federally funded treatment program for drug-involved offenders identified a small sample (n = 6) of butane hash oil users and generated focus group interview data on the nature of butane hash oil, the practice of dabbing, and its effects. Findings inform discussion of additional research needed on butane hash oil and its implications for the ongoing marijuana legalization debate, including the diversity of users, routes of administration, and differences between retail/medical and prohibition states. PMID- 26800052 TI - AN EMPIRICAL EVALUATION OF FACTOR RELIABILITY. AB - The psychometric reliability of a factor, defined as its generalizability across samples drawn from the same population of tests, is considered as a necessary precondition for the scientific meaningfulness of factor analytic results. A solution to the problem of generalizability is illustrated empirically on data from a set of tests designed to measure facets of response styles and of personality dimensions. Parallel sets of measures based on personality scales defining each of seven factors were separakely factored. Independent sets of component scores derived from the orthogonal least squares fit to the oblique factor pattern matrix were computed, and these component scores were intercorrelated between the two sets, yielding factor reliabilities, whose values ranged from .66 to .86 (p < .0001, for each factor). A corresponding analysis based on scores derived from random binary data yielded nonsignificant factor reliabilities ranging from -.12 to +.07. It was recommended that such a test of factor generalizability be incorporated routinely into fador analytic investigations, particularly those employing Procrustes-type rotations. PMID- 26800053 TI - THE INVESTIGATION OF COGNITIVE MODELS FOR INVENTORY RESPONSE. AB - This research centers around a family of models designed to describe individuals' responses to personality inventory responses. The models are all alternative ways of relating the individual's degree of endorsement of the items to their locations on dimensions of semantic meaning as he perceives them. In the present study, the relationships among individuals' responses to adjective check list items and multidimensional scaling analyses of similarity judgments of the same items were studied. For each individual, a multiple correlation was computed between his endorsement of the items and their locations on dimensions. The median R, corrected for the number of predictors, was .81 in the case of "candid" endorsements and .92 for endorsements under a faking set. These correlations are comparable to the consistencies in endorsement across repetitions of the same items. Implications for a personality measurement theory are discussed. PMID- 26800051 TI - Partially Defective Store Operated Calcium Entry and Hem(ITAM) Signaling in Platelets of Serotonin Transporter Deficient Mice. AB - BACKGROUND: Serotonin (5-hydroxytryptamin, 5-HT) is an indolamine platelet agonist, biochemically derived from tryptophan. 5-HT is secreted from the enterochromaffin cells into the gastrointestinal tract and blood. Blood 5-HT has been proposed to regulate hemostasis by acting as a vasoconstrictor and by triggering platelet signaling through 5-HT receptor 2A (5HTR2A). Although platelets do not synthetize 5-HT, they take 5-HT up from the blood and store it in their dense granules which are secreted upon platelet activation. OBJECTIVE: To identify the molecular composite of the 5-HT uptake system in platelets and elucidate the role of platelet released 5-HT in thrombosis and ischemic stroke. METHODS: 5-HT transporter knockout mice (5Htt-/-) were analyzed in different in vitro and in vivo assays and in a model of ischemic stroke. RESULTS: In 5Htt-/- platelets, 5-HT uptake from the blood was completely abolished and agonist induced Ca2+ influx through store operated Ca2+ entry (SOCE), integrin activation, degranulation and aggregation responses to glycoprotein VI (GPVI) and C-type lectin-like receptor 2 (CLEC-2) were reduced. These observed in vitro defects in 5Htt-/- platelets could be normalized by the addition of exogenous 5 HT. Moreover, reduced 5-HT levels in the plasma, an increased bleeding time and the formation of unstable thrombi were observed ex vivo under flow and in vivo in the abdominal aorta and carotid artery of 5Htt-/- mice. Surprisingly, in the transient middle cerebral artery occlusion (tMCAO) model of ischemic stroke 5Htt /- mice showed nearly normal infarct volume and the neurological outcome was comparable to control mice. CONCLUSION: Although secreted platelet 5-HT does not appear to play a crucial role in the development of reperfusion injury after stroke, it is essential to amplify the second phase of platelet activation through SOCE and plays an important role in thrombus stabilization. PMID- 26800054 TI - MODES OF INTERPERSONAL RESPONSE TO PEERS. AB - The study sought to (a) identify the main response patterns elicited by six types of interpersonal stimuli, and (a) test the effect of varying the sex of the agent and the age of the respondent. A Schedule of Interpersonal Response (SIR) designed to reflect the six classes of stimuli and two to four possible response modes was constructed. A factor analysis of 70 homogeneous subtests yielded five interpretable factors. Samples of working adults, college students and high school students of both sexes were compared as to response pattern. Evidence of concurrent validity was found in scores on Stern's Activities Index. PMID- 26800055 TI - SOME NOTES ON THE NUMBER OF FACTORS PROBLEM. AB - The epistemological status of factors-that is, components, common factors, and image factors-is briefly discussed. Implications for the number of factors problem, for varying views of factor analysis, and for the particular factor analytic model employed are noted; and the rationales under- lying the best known decision rules regarding the correct number of factors are discussed. The paper presents the results of a study in which reanalyses were performed on 17 correlation matrices found in the literature, and eight well-known rules and one new rule for determining the correct number of factors were applied. The rules are compared in light of the factor analytic model implied in each case, and some implications for practice are noted. PMID- 26800056 TI - ON EXTENSION ANALYSIS AND ITS RELATION TO CORRELATIONS BETWEEN VARIABLES AND FACTOR SCORES. AB - Given the intercorrelations among variables that are factored (core variables) and variables that are excluded from a factor analysis (extension variables), matrix algebra algorithms are developed for obtaining the correlations between the extension variables and the factor scores that would be computed by what is called the direct method for obtaining factor scores. The equations needed to obtain such extension analysis results are provided for the case of oblique factors and when either the primary factor or reference vector method of rotation is used. PMID- 26800057 TI - THE EFFECT OF FACTOR SCORES, GUTTMAN SCORES, AND SIMPLE SUM SCORES ON THE SIZE OF F RATIOS IN AN ANALYSIS O F VARIANCE DESIGN. AB - Many questions in the social sciences reduce to a comparison of mean values across groups in a classical analysis of variance F test. Often the original data my come from a set of items in a questionnaire or personality inventory. When this occurs, some sort of data reduction, combining of items, or scaling procedure is first performed before the hypothesis of no difference in mean values across groups can be made. In many cases, this problem causes undue concern t0 a researcher because the effect of the scoring procedure on the distribution of F is not clear. To help solve this problem, this study was undertaken to investigate whether the method used to calculate scores has any effect on the magnitude of the F ratio in an analysis of variance, for, if it were shown that no statistical difference existd, then a researcher would have some justification for showing the procedure having minimal messes. On the other hand, if statistical differences were b arise because of the kind d scaling procedure employed, then a researcher would have to be more cautious in his choice. For this empirical investigation, Guttman, Saaotor, and simple sum scores were generated using item responses from a large pool of high school seniors. No difference in scoring method was detected when the F ratios resulting from each of the three scoring methods were analyzed. This suggests that, for chin analyses, a simple sum score may be as effective as mres derived by more complicated methods. PMID- 26800058 TI - AN APPLICATION OF THE TAXONOME METHOD TO A PLASMODE. AB - The concept of a plasmode, described as a numerical set of data (preferably from a physical example) arranged to fit a scientific model, is developed and its usefulness discussed. A plasmode consisting of physical measurements on several varieties of musical instruments is used to explore the utility of the Taxonome computer program for locating types. Known segregations preinserted were successfully reproduced by this objective computerized approach. PMID- 26800059 TI - A TABLE OF EXPECTED STRESS VALUES FOR RANDOM RANKINGS IN NONMETRIC MULTIDIMENSIONAL SCALING. AB - The results of applying a nonmetric multidimensional scaling algorithm to sets of pseudo random data are used as the basis for constructing, by means of regression techniques, a table which will assist a user to decide whether empirically obtained data sets are the result of a random process. The table covers the range from 12 to 48 objects (points) for one to five recovered dimensions. PMID- 26800060 TI - BRIEF REPORT: ADDITIONAL DATA ON DISTORTION DUE TO AGGREGATION IN NONMETRIC MULTIDIMENSIONAL SCALING. AB - A previous research report investigated the effect of aggregation on nonmetric multidimensional scaling solutions in which the scaled stimuli were adjectives. Aggregate solution configurations were found to resemble substantially the configurations based on individual similarity data. However, recent replications on nonadjectival stimuli indicate substantial distortion due to aggregation. Preliminary conjectures are made about the adjective- object differences. The importance of the issue for multidimensional scaling is underscored by citing recent developments in scaling techniques. PMID- 26800061 TI - Safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (STELLA-ELDER): Interim results of a post-marketing surveillance study. AB - OBJECTIVE: To determine the incidence of adverse drug reactions (ADRs) associated with ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: We report interim results of a postmarketing surveillance survey. Japanese physicians recorded ADRs in elderly patients (>= 65 years old) who were first prescribed with ipragliflozin within 3 months of its launch (April 2014). MAIN OUTCOME MEASURES: Incidence of ADRs within 1 year of starting treatment with ipragliflozin. RESULTS: 898 ADRs occurred in 721/7,170 patients (10.06%). Skin complication-, volume depletion-, genital infection-, polyuria/pollakiuria-, urinary tract infection-, and hypoglycemia-related ADRs occurred in 2.23%, 1.90%, 1.45%, 1.32%, 0.77%, and 0.32%, respectively. ADRs were classified as serious in 44 (0.61%) patients. Half of the ADRs occurred within 30 days of starting treatment. There were no cases of Stevens-Johnson syndrome or toxic epidermal necrolysis. Most (92.1%) of the ADRs resolved or improved. Glycated hemoglobin, fasting blood glucose, body weight, and systolic blood pressure decreased by 0.6% (baseline 7.8%), 22.7 mg/dL (baseline 163.0 mg/dL), 2.3 kg (baseline 67.4 kg), and 3.1 mmHg (baseline 133.2 mmHg), respectively, from baseline to treatment discontinuation/last visit. CONCLUSIONS: Ipragliflozin is well tolerated and reduced surrogate endpoints in elderly Japanese patients with type 2 diabetes mellitus. Clinicaltrials.gov identifier: NCT02297620. PMID- 26800063 TI - [Advantages of Ticagrelor outweigh also in COPD patients]. PMID- 26800064 TI - [Rather ignore than resect small colorectal polyps?]. PMID- 26800065 TI - [Is more vitamin D automatically better?]. PMID- 26800066 TI - [32-year-old patient with growing oral finding]. PMID- 26800067 TI - [Early diagnosis--successful treatment]. PMID- 26800068 TI - [Imaging procedures for myocarditis and cardiomyopathy]. AB - This manuscript gives a comprehensive overview with regard to cardiac imaging techniques for work-up and management of patients with myocarditis or cardiomyopathies. PMID- 26800069 TI - [Myocarditis and inflammatory cardiomyopathy--current treatment options]. AB - Myocarditis is a cardiac inflammatory disease mainly caused by autoimmune processes and/or viral infections. Despite the advances of non-invasive diagnostic tests, endomyocardial biopsies (EMBs) remains the gold standard diagnostic technique for myocarditis and inflammatory cardiomyopathy. If the immune response fails to eliminate the infectious agent or inflammatory process does not resolve, only EMB can elucidate the cause and the status of the disease. Such tissue analyses are the prerequisite for an initiation of a specific antiviral or an anti-inflammatory treatment in addition to basic heart failure therapy. Other conditions such as giant cell myocarditis or cardiac sarcoidosis benefit from an anti-inflammatory treatment during the acute phase, so EMB has an important role both in acute and chronic settings. Despite the promising results with immunosuppressive or antiviral therapy in specific clinical scenarios according to published data, larger randomized studies are warranted in order to detect the effect of these treatments in strong clinical endpoints. PMID- 26800070 TI - [Pharmaca Induced Cardiac Injury]. AB - Many drugs influence vital functions via the sympathetic and the parasympathetic system. Besides that hypersensitivity reactions and reactions by chemical radicals that arise in drug metabolism may directly harm the heart muscle cell. Cardiac adverse drug reactions (ADR) result in disturbances of the heart rhythm, negative inotropic effects, direct damage to the heart muscle cell, and reduced perfusion of heart tissue. Their importance is often neglected because pharmacologically similar drugs are licensed for completely different indications. This is of particular interest if more drugs are prescribed in combination. Now these effects may add up to pharmacodynamic drug-drug interactions. Data banks like PSIAConline (www.psiac.de), individualization of drug prescription by therapeutic drug monitoring (TDM) combined with a clinical pharmacological report (www.konbest.de), as well as drug information systems such as AGATE (www.amuep-agate.de) are today of help not just to recognize such drug risks, but also to find professional and evidence based solutions for it. PMID- 26800071 TI - [Cardiovascular disease in pregnancy]. AB - Cardiovascular diseases are among the most frequent complications in pregnancies. Among them preexisting heart diseases including congenital heart disease, genetic cardiomyopathies, myocardial infarction and chemotherapy-induced cardiomyopathies display a special challenge for the mother and her physicians. Moreover, the incidence of cardiovascular disease induced by or associated with pregnancy, i.e. hypertensive disorders and peripartum cardiomyopathies, has increased over the past decades. In the present overview we explain why pregnancy is a stress model for the maternal heart and summarize the current knowledge on the influence of pregnancy on preexisting cardiomyopathies. We highlight recent advances in research with regard to hypertensive complications in pregnancy and peripartum cardiomyopathy (PPCM). Moreover, we summarize etiologies, risk factors, pathomechanisms, diagnosis, treatment, management and prognosis. Finally, interdisciplinarity between different clinical fields and basic science is a key requirement to avoid longterm damage to the cardiovascular system induced by pregnancy associated impacts and with this improve women's health in general. PMID- 26800072 TI - [Suprapubic catheter insertion]. AB - The suprapubic catheter enables a percutaneous drainage of urine. The insertion is made superior of the pubic bone through the abdominal wall into the bladder. It allows a permanent drainage of urine bypassing the urethra. The insertion of a suprapubic catheter requires knowledge and expertise. This paper summarizes the basic background and allows to follow the practical application step by step. PMID- 26800073 TI - [Diastolic heart failure treated by diet]. AB - History and admission findings | An obese patient with type 2 diabetes (on 90 IU insulin daily) and exertional dyspnoea (NYHA II-III) for 3 weeks presented in a rehabilitation clinic hoping to reduce his weight. Clinical and laboratory findings excluded any inflammatory or systemic disease apart from diabetes mellitus. Blood pressure and serum lipid levels were normal. Investigations | An unremarkable ECG stress test and echocardiogram excluded ischemic and hypertensive heart disease and primary cardiomyopathy. Pulsed tissue Doppler revealed diastolic cardiac dysfunction. Unremarkable were also chest X-ray, pulmonary function testing and 24-hour ECG. Treatment and Course | The findings supported the diagnosis of HFpEF and diabetic/insulin resistance cardiomyopathy. Insulin resistance was treated for three weeks by low-carbohydrate nutrition and moderate exercise. At discharge, weight was reduced by 2 kg, exercise capacity and diastolic function were normalized, as were insulin resistance and postprandial glucose levels, whilst antidiabetic therapy was reduced to low carbohydrate nutrition. Conclusion | HFpEF due to insulin resistance cardiomyopathy is often not recognized, especially in obese individuals, and may be further aggravated by the traditional recommendation of low-fat nutrition. Due to the high reversibility of metabolically dysregulated cardiovascular mechanisms, a causal, i.e. metabolic therapeutic strategy that normalizes insulin resistance by low-carbohydrate nutrition is a promising option. PMID- 26800074 TI - [Frequent non-medical cannabis use: health sequelae and effectiveness of detoxification treatment]. AB - The non-medical (recreational) use of cannabis is common particularly among young adults. In light of the ongoing legalization debate the clinical impact of physical and psychosocial consequences of regular recreational cannabis consumption should be presented. Health consequences appear to be more pronounced the earlier the regular recreational cannabis use had been started in the individual's development. There is an increasing demand from recreational cannabis users for medical treatment of cannabis-related complaints including the cannabis withdrawal syndrome. Physical sequelae such as chronic bronchitis, cyclical hyperemesis and fertility problems are usually reversible along with abstinence. The often debilitating cannabis-related mental and cognitive complaints respond on a qualified inpatient detoxification treatment with high effect sizes (Cohen's d 0.7 -1.4). The severity of the cannabis addiction benefits sustainably from psychotherapeutic approaches and individual psychosocial counseling (Cohen's d 0,5-1,2). Currently, the actual health hazard of recreational cannabis use was evaluated by addiction experts to be significantly lower than that of tobacco or alcohol use. PMID- 26800075 TI - [Pay for performance approach and its possible future influence on revenues in German interventional cardiology units]. AB - Pay-for-performance in German health care system is still uncommon but--in view of scheduled legislative projects--could gain more influence in future. Beside others, risc adjusted in-hospital mortality and the door-to-ballon-time inpatients with ST-elevation myocardial infarction could become quality- and performance indicators in interventional cardiology units. As a result, process optimization based on these indicators could have an impact on both patient value (as already today) and revenues (from 2017 onwards). PMID- 26800076 TI - [State of integration of palliative care at Comprehensive Cancer Centers funded by German Cancer Aid]. AB - BACKGROUND: Similarities and differences of integration of palliative care in clinical care, research and education structures at German Comprehensive Cancer Centers (CCC) are not known in detail. OBJECTIVE: Provide an overview of availability and the way of integration of specialized palliative care at CCCs funded by the German Cancer Aid (Deutsche Krebshilfe, DKH). METHOD: We conducted structured interviews from May to August 2014 with heads of palliative care departments (personally or by telephone). The interviews included a quantitative and a qualitative part. Other stakeholders of CCCs were asked the questions of the qualitative part. We evaluated the qualitative data using the content analysis by Mayring and MAXQDA 11.0. SPSS 21.0 was used for quantitative analysis. RESULTS: 26 interviews were realized in 13 CCCs with 14 sites, which received funding, by DKH till August 2014 (one CCC had two university hospitals). Of these, 12 sites had a palliative care unit (86%), 11 sites had palliative care consulting services available (79%). Participation of palliative care specialists in tumor boards is not provided in 3 institutions (21%) and is often not feasible on regular basis in the other institutions, due to staffing shortage. In 7 sites (50%) defined criteria to integrate palliative care into CCCs were available. In the last 5 years specialized palliative care of 4 sites received an invitation for a research project by another department within the CCC (29%). 10 sites (71%) had started own palliative care research projects. Chairs in palliative care were available in 4 CCCs (29%). CONCLUSION: The extent and depth of palliative care integration in the 14 CCC sites is heterogeneous. PMID- 26800077 TI - [Clinical practice of dual antiplatelet therapy after percutaneous peripheral arterial interventions in Germany]. AB - BACKGROUND AND AIM: Guideline recommendations regarding antithrombotic treatment with two antiplatelet agents (dual antiplatelet treatment) after peripheral interventional procedures are vague due to missing data from clinical trials. METHODS: 212 vascular centres in germany were evaluated regarding dual antiplatelet treatment using a standardized questionnaire with differentiation of localisation of the treated artery and interventional methods being used. RESULTS: 89 (42%) questionnaires returned completed. Application and duration of dual antiplatelet treatment after peripheral interventional procedures were quite different regarding interventional methods used (PTA: percutaneous transluminal angioplasty, DCB-PTA: drug coated ballon, Stenting, DES: drug eluting stent, Atherectomy). Mean duration of dual antiplatelet treatment were: PTA iliacal/femoro-popliteal 0 month, crural 1 month; DCB-Intervention and stenting: iliacal 1 month, femoro-popliteal 1,5 months, crural 2 months; DE-stenting iliacal 1,5 months, femoro-popliteal/crural 3 months and after femoro-popliteal / crural atherectomy 1 month. CONCLUSION: Data about dual antiplatelet treatment after peripheral interventional procedures are sparse. PMID- 26800078 TI - Response to rituximab in B-CLL patients is adversely impacted by frequency of IL 10 competent B cells and FcgammaRIIIa polymorphism. A study of FCGCLL/WM and GOELAMS groups. PMID- 26800080 TI - On the automaticity of response inhibition in individuals with alcoholism. AB - BACKGROUND AND OBJECTIVES: Response inhibition is usually considered a hallmark of executive control. However, recent work indicates that stop performance can become associatively mediated ('automatic') over practice. This study investigated automatic response inhibition in sober and recently detoxified individuals with alcoholism.. METHODS: We administered to forty recently detoxified alcoholics and forty healthy participants a modified stop-signal task that consisted of a training phase in which a subset of the stimuli was consistently associated with stopping or going, and a test phase in which this mapping was reversed. RESULTS: In the training phase, stop performance improved for the consistent stop stimuli, compared with control stimuli that were not associated with going or stopping. In the test phase, go performance tended to be impaired for old stop stimuli. Combined, these findings support the automatic inhibition hypothesis. Importantly, performance was similar in both groups, which indicates that automatic inhibitory control develops normally in individuals with alcoholism.. LIMITATIONS: This finding is specific to individuals with alcoholism without other psychiatric disorders, which is rather atypical and prevents generalization. Personalized stimuli with a stronger affective content should be used in future studies. CONCLUSIONS: These results advance our understanding of behavioral inhibition in individuals with alcoholism. Furthermore, intact automatic inhibitory control may be an important element of successful cognitive remediation of addictive behaviors.. PMID- 26800082 TI - Simultaneous Enhancement of Efficiency and Stability of Phosphorescent OLEDs Based on Efficient Forster Energy Transfer from Interface Exciplex. AB - Exciplex forming cohosts have been widely adopted in phosphorescent organic light emitting diodes (PHOLEDs), achieving high efficiency with low roll-off and low driving voltage. However, the influence of the exciplex-forming hosts on the lifetimes of the devices, which is one of the essential characteristics, remains unclear. Here, we compare the influence of the bulk exciplex and interface exciplex on the performances of the devices, demonstrating highly efficient orange PHOLEDs with long lifetime at low dopant concentration by efficient Forster energy transfer from the interface exciplex. A bipolar host, (3'-(4,6 diphenyl-1,3,5-triazin-2-yl)-(1,1'-biphenyl)-3-yl)-9-carbazole (CzTrz), was adopted to combine with a donor molecule, tris(4-(9H-carbazol-9-yl)phenyl)amine (TCTA), to form exciplex. Devices with energy transfer from the interface exciplex achieve lifetime almost 2 orders of magnitude higher than the ones based on bulk exciplex as the host by avoiding the formation of the donor excited states. Moreover, a highest EQE of 27% was obtained at the dopant concentration as low as 3 wt % for a device with interface exciplex, which is favorable for reducing the cost of fabrication. We believe that our work may shed light on future development of ideal OLEDs with high efficiency, long-lifetime, low roll off and low cost simultaneously. PMID- 26800081 TI - Rapid and Highly Sensitive Detection of Variant Creutzfeldt-Jakob Disease Abnormal Prion Protein on Steel Surfaces by Protein Misfolding Cyclic Amplification: Application to Prion Decontamination Studies. AB - The prevalence of variant Creutzfeldt-Jakob disease (vCJD) in the population remains uncertain, although it has been estimated that 1 in 2000 people in the United Kingdom are positive for abnormal prion protein (PrPTSE) by a recent survey of archived appendix tissues. The prominent lymphotropism of vCJD prions raises the possibility that some surgical procedures may be at risk of iatrogenic vCJD transmission in healthcare facilities. It is therefore vital that decontamination procedures applied to medical devices before their reprocessing are thoroughly validated. A current limitation is the lack of a rapid model permissive to human prions. Here, we developed a prion detection assay based on protein misfolding cyclic amplification (PMCA) technology combined with stainless steel wire surfaces as carriers of prions (Surf-PMCA). This assay allowed the specific detection of minute quantities (10-8 brain dilution) of either human vCJD or ovine scrapie PrPTSE adsorbed onto a single steel wire, within a two week timeframe. Using Surf-PMCA we evaluated the performance of several reference and commercially available prion-specific decontamination procedures. Surprisingly, we found the efficiency of several marketed reagents to remove human vCJD PrPTSE was lower than expected. Overall, our results demonstrate that Surf-PMCA can be used as a rapid and ultrasensitive assay for the detection of human vCJD PrPTSE adsorbed onto a metallic surface, therefore facilitating the development and validation of decontamination procedures against human prions. PMID- 26800083 TI - Monoliths in capillary electrochromatography and capillary liquid chromatography in conjunction with mass spectrometry. AB - Here, we have reviewed separation studies utilizing monolithic capillary columns for separation of compounds preceding MS analysis. The review is divided in two parts according to the used separation method, namely CEC and capillary LC (cLC). Based on our overview, monolithic CEC-MS technique have been more focused on the syntheses of highly specialized and selective separation phase materials for fast and efficient separation of specific types of analytes. In contrast, monolithic cLC-MS is more widely used and is often employed, for instance, in the analysis of oligonucleotides, metabolites, and peptides and proteins in proteomic studies. While poly(styrene-divinylbenzene)-based and silica-based monolithic capillaries found their place in proteomic analyses, the other laboratory-synthesized monoliths still wait for their wider utilization in routine analyses. The development of new monolithic materials will most likely continue due to the demand of more efficient and rapid separation of increasingly complex samples. PMID- 26800084 TI - Atrial Fibrillation Management Strategies in Routine Clinical Practice: Insights from the International RealiseAF Survey. AB - BACKGROUND: Atrial fibrillation (AF) can be managed with rhythm- or rate-control strategies. There are few data from routine clinical practice on the frequency with which each strategy is used and their correlates in terms of patients' clinical characteristics, AF control, and symptom burden. METHODS: RealiseAF was an international, cross-sectional, observational survey of 11,198 patients with AF. The aim of this analysis was to describe patient profiles and symptoms according to the AF management strategy used. A multivariate logistic regression identified factors associated with AF management strategy at the end of the visit. RESULTS: Among 10,497 eligible patients, 53.7% used a rate-control strategy, compared with 34.5% who used a rhythm-control strategy. In 11.8% of patients, no clear strategy was stated. The proportion of patients with AF related symptoms (EHRA Class > = II) was 78.1% (n = 4396/5630) for those using a rate-control strategy vs. 67.8% for those using a rhythm-control strategy (p<0.001). Multivariate logistic regression analysis revealed that age <75 years or the paroxysmal or persistent form of AF favored the choice of a rhythm-control strategy. A change in strategy was infrequent, even in patients with European Heart Rhythm Association (EHRA) Class > = II. CONCLUSIONS: In the RealiseAF routine clinical practice survey, rate control was more commonly used than rhythm control, and a change in strategy was uncommon, even in symptomatic patients. In almost 12% of patients, no clear strategy was stated. Physician awareness regarding optimal management strategies for AF may be improved. PMID- 26800085 TI - Pulse Oximetry Overestimates Oxyhemoglobin in Neonates with Critical Congenital Heart Disease. AB - BACKGROUND: Pulse oximetry is a key part of the clinical evaluation and management of neonates with congenital heart defects. In 2011, the US Department of Health and Human Services recommended use of routine pulse oximetry to screen for critical congenital heart disease (CCHD). Current studies suggest pulse oximetry overestimates arterial oxygen saturation in moderately hypoxemic pediatric patients. Based on variable hypoxemia in neonates with CCHD, concern exists that present pulse oximeter technology may overestimate measured oxyhemoglobin. OBJECTIVES: To compare pulse oximetry and oxyhemoglobin values in NICU patients with known CCHD to evaluate the ability of pulse oximetry to reliably predict oxyhemoglobin accounting for potential confounding variables such as heart lesion, saturation range, total hemoglobin concentration, peripheral perfusion, and timing of measurements. METHODS: This is a single center retrospective study. Inclusion criteria were AHA-defined CCHD and umbilical artery blood gas-derived oxyhemoglobin with concurrent pulse oximetry recording during hours of life 0-72. Bland-Altman analysis and the concordance correlation coefficient were used to measure the internal consistency (agreement) between the two measurements. RESULTS: 89 patients were evaluated with 599 paired arterial oxyhemoglobin and pulse oximetry recordings. 47% of all pulse oximetry values were >=95% - the cutoff for CCHD screening. Pulse oximetry overestimated arterial oxyhemoglobin by a mean of 5.4% over all levels of oxygen saturation. Pulse oximetry overestimation was >3 in 65.4% of measurements, >6 in 41.2% of measurements, and >10 in 15.3% of measurements. Hour of life, total hemoglobin, and peripheral perfusion did not significantly affect the degree of overestimation. CONCLUSIONS: Our results reinforce the concern that present pulse oximeters overestimate oxyhemoglobin values, contributing to some false-negative CCHD screens and potentially leading to unnecessary escalations in care of those patients with diagnosed CCHD. Improvements in pulse oximetry accuracy and precision in the neonate would benefit both screening and clinical care in the NICU. PMID- 26800086 TI - Characterization of Long-Term Cultured Murine Submandibular Gland Epithelial Cells. AB - PURPOSE: Human and rat salivary gland cell lines derived from tumors or genetic modification are currently available for research. Here, we attempted to culture and characterize long-term cultured cells spontaneously derived from wild type murine submandibular glands (SGs). METHODS: SGs were removed from 3-week-old C57B/6J female mice and dissociated by collagenase type 1 and hyaluronidase digestion. Isolated SG epithelial cells were cultured in low calcium, serum-free growth media in the presence of cholera toxin (CT) during early passages. Single cell colonies were isolated by limiting dilution culture after 25 passages. Early and late-stage cell cultures were characterized for keratin 14, keratin 18, alpha-smooth muscle actin, and p63 by immunostaining and quantitative real-time PCR analysis. RESULTS: SG epithelial cells cultured in optimized media maintained their proliferative ability and morphology for over 80 passages. Long-term cultured cells expressed keratin 14, keratin 18, and p63, indicative of an epithelial phenotype. CONCLUSIONS: Epithelial cells originating from wild type murine SGs could be cultured for longer periods of time and remain phenotypically similar to ductal basal epithelium. PMID- 26800087 TI - Knee and ankle biomechanics with lateral wedges with and without a custom arch support in those with medial knee osteoarthritis and flat feet. AB - This study compared immediate changes in knee and ankle/subtalar biomechanics with lateral wedge orthotics with and without custom arch support in people with knee osteoarthritis and flat feet. Twenty-six participants with radiographic evidence of medial knee osteoarthritis (22 females; age 64.0 years [SD 8.0 years], BMI 27.2 kg/m(2) [4.2]) and flat feet (median foot posture index = + 5) underwent three-dimensional gait analysis for three conditions: Control (no orthotic), lateral wedge, and lateral wedge plus arch support. Condition order was randomized. Outcomes included frontal plane knee and ankle/subtalar biomechanics, and comfort. Compared to the control, lateral wedge and lateral wedge with arch support reduced the knee adduction moment impulse by 8% and 6%, respectively (p < 0.05). However, the lateral wedge resulted in a more everted foot position (4.3 degrees) than lateral wedge plus arch support (3.2 degrees) (p < 0.05). In contrast, lateral wedge plus arch support reduced foot frontal plane excursion compared to other conditions (p < 0.05). Participants self-reported significantly more immediate comfort with lateral wedge plus arch support compared to the control, whereas there was no difference in self-reported comfort between lateral wedge and control. No immediate changes in knee pain were observed in any condition. CLINICAL SIGNIFICANCE: Rather than prescribing lateral wedges to all patients with knee osteoarthritis, those who have medial knee osteoarthritis and flat feet may prefer to use the combined orthotic to reduce loads across the knee, and to minimize the risk of foot and ankle symptoms as a consequence of orthotic treatment. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1597-1605, 2016. PMID- 26800089 TI - Direct Arylation of Pyrroles via Indirect Electroreductive C-H Functionalization Using Perylene Bisimide as an Electron-Transfer Mediator. AB - The indirect electroreductive coupling of aryl halides and pyrroles was successfully conducted using a catalytic amount of perylene bisimide as a mediator in 1-ethyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl)imide ([EMIM]NTf2)/DMSO. PMID- 26800090 TI - Middle Cerebral Artery Pulsatility Index is Associated with Cognitive Impairment in Lacunar Stroke. AB - BACKGROUND AND PURPOSE: Pulsatility index (PI) of the middle cerebral artery is postulated to reflect the vascular resistance in the artery distal of the probe, and has been reported to increase in small vessel disease, diabetes mellitus, ageing, and dementia. Lacunar infarcts are considered to be related to cognitive impairment. We therefore conducted a study to assess the association between cognitive impairment and PI in patients with a lacunar infarct. METHODS: Consecutive patients presenting with an acute lacunar syndrome who were admitted to the stroke unit were enrolled. The patients were examined with Doppler ultrasonography of the intracranial arteries, and the PI of the middle cerebral artery was recorded. Cognitive function was evaluated by mini-mental state examination (MMSE), clock drawing test, and trail making test (TMT) A and B. RESULTS: Among the 113 patients included, 85 patients had an acute lacunar infarct and 28 had one or more nonlacunar infarcts. The mean PI was 1.46 (SD = .33). PI was significantly (P < .05) associated with MMSE, TMT A and TMT B in patients with lacunar infarct, even after adjustment for multiple patient characteristics (age, sex, prestroke hypertension, smoking, previous stroke, and diabetes). CONCLUSIONS: PI was associated with the cognitive performance in patients with lacunar infarcts and a lacunar syndrome. An elevated PI may be related to impairment in several cognitive domains. These findings suggest that transcranial Doppler ultrasonography could be an adjunct tool for early diagnosis of cognitive impairment after stroke. PMID- 26800092 TI - A protocol to develop clinical guidelines for inclusion-body myositis. AB - INTRODUCTION: Inclusion-body myositis (IBM) is a late-onset idiopathic inflammatory myopathy associated with selective and progressive muscle weakness and atrophy. Current clinical management of IBM is largely supportive due to its uncertain etiology and lack of effective treatment. Establishing a consensus of opinion on questions relating to diagnosis and management of IBM is expected to help reduce inconsistencies in the care and resources allocated to those living with this condition. METHODS: A protocol has been developed to produce best practice clinical guidelines for IBM based on a combination of published research and expert consensus. CONCLUSIONS: In this study we describe the proposed protocol for developing methods for producing robust and transparent clinical guidance on aspects of diagnosis, drug treatment, physical and practical management, respiration, nutrition and cardiac management, psychosocial management, and multidisciplinary care. PMID- 26800093 TI - Cross-cultural care encounters in paediatric care: minority ethnic parents' experiences. AB - BACKGROUND: Because of worldwide migration, the healthcare staff in general as well as in paedi"atric care specifically is challenged increasingly by people from various ethnic backgrounds. The challenge is related to providing culturally competent care and effectively communicating with people from diverse cultural and ethnic backgrounds who have different health beliefs, practices, values and languages. This also applies to the Swedish society and to Swedish paediatric care. AIM: The purpose of this study was to describe the expectations and experiences of cross-cultural care encounters among minority ethnic parents in Swedish paediatric care. METHOD: A qualitative design was used in the study. Data were collected using semi-structured interviews between October 2011 and March 2012. The sample consisted of 12 parents of minority ethnic backgrounds who had their child in a ward at a children's hospital in the Stockholm County Council. The interviews were analysed using manifest content analysis. ETHICAL CONSIDERATIONS: The Regional Ethical Review Committee approved the study (Ref: Nr: 2011/927-31/5). RESULTS: The analysis of the interviews led to three categories: fundamentals in nursing, cultural sensitivity and understanding, and influencing conditions. CONCLUSIONS: Generic knowledge and skills of nurses outweighed the need for the nurses to have culture-specific knowledge of their patients or relatives in cross-cultural care encounters. Language skills and the availability of bilingual nurses in a multi-ethnic society can facilitate communication and increase parents' satisfaction in cross-cultural care encounters. PMID- 26800094 TI - Location Isn't Everything: Proximity, Hospital Characteristics, Choice of Hospital, and Disparities for Breast Cancer Surgery Patients. AB - OBJECTIVE: Assess the relative importance of proximity and other hospital characteristics in the choice of hospital for breast cancer surgery by race/ethnicity. DATA: SEER-Medicare data. STUDY DESIGN: Observational study of women aged >65 years receiving surgery for stage I/II/III breast cancer diagnosed in 1992-2007 in Detroit (N = 10,746 white/black), Atlanta (N = 4,018 white/black), Los Angeles (N = 9,433 white/black/Asian/Hispanic), and San Francisco (N = 4,856 white/black/Asian). We calculated the distance from each patient's census tract of residence to each area hospital. We estimated discrete choice models for the probability of receiving surgery at each hospital based on distance and assessed whether deviations from these predictions entailed interactions of hospital characteristics with the patient's race/ethnicity. We identified high-quality hospitals by rates of adjuvant radiation therapy and by survey measures of patient experiences, and we assessed how observed surgery rates at high-quality hospitals deviated from those predicted based on distance alone. PRINCIPAL FINDINGS: Proximity was significantly associated with hospital choice in all areas. Minority more often than white breast cancer patients had surgery at hospitals with more minority patients, those treating more Medicaid patients, and in some areas, lower quality hospitals. CONCLUSIONS: Residential location alone does not explain concentration of racial/ethnic-minority breast cancer surgery patients in certain hospitals that are sometimes of lower quality. PMID- 26800095 TI - Tunable, Strain-Controlled Nanoporous MoS2 Filter for Water Desalination. AB - The deteriorating state of global fresh water resources represents one of the most serious challenges that scientists and policymakers currently face. Desalination technologies, which are designed to extract potable water from the planet's bountiful stores of seawater, could serve to alleviate much of the stress that presently plagues fresh water supplies. In recent decades, desalination methods have improved via water-filtering architectures based on nanoporous graphene filters and artificial membranes integrated with biological water channels. Here, we report the auspicious performance (in simulations) of an alternative nanoporous desalination filter constructed from a MoS2 nanosheet. In striking contrast to graphene-based filters, we find that the "open" and "closed" states of the MoS2 filter can be regulated by the introduction of mechanical strain, yielding a highly tunable nanopore interface. By applying lateral strain to the MoS2 filter in our simulations, we see that the transition point between "open" and "closed" states occurs under tension that induces about 6% cross sectional expansion in the membrane (6% strain); the open state of the MoS2 filter demonstrates high water transparency and a strong salt filtering capability even under 12% strain. Our results thus demonstrate the promise of a controllable nanoporous MoS2 desalination filter, wherein the morphology and size of the central nanopore can be precisely regulated by tensile strain. These findings support the design and proliferation of tunable nanodevices for filtration and other applications. PMID- 26800097 TI - MiR-146a modulates macrophage polarization by inhibiting Notch1 pathway in RAW264.7 macrophages. AB - Macrophages are heterogeneous and plastic cells which are able to undergo dynamic transition between M1 and M2 polarized phenotypes in response to the microenvironment signals. However, the underlying molecular mechanisms of macrophage polarization are still obscure. In the current study, it was revealed that miR-146a might play a pivotal role in macrophage polarization. As our results indicated, miR-146a was highly expressed in M2 macrophages rather than M1 macrophages. Over-expression of miR-146a resulted in significantly decreased production of pro-inflammatory cytokines including iNOS and TNF-alpha in M1 macrophages, while increased production of M2 marker genes such as Arg1 and CD206 in M2 macrophages. In contrast, knockdown of miR-146a promoted M1 macrophage polarization but diminished M2 macrophage polarization. Mechanistically, it was revealed that miR-146a modulated macrophage polarization by targeting Notch1. Of note, PPARgamma was responsible as another target for miR-146a-mediated macrophage polarization. Taken together, it was suggested that miR-146a might serve as a molecular regulator in macrophage polarization and is a potential therapeutic target for inflammatory diseases. PMID- 26800098 TI - Protective effects of pogostone against LPS-induced acute lung injury in mice via regulation of Keap1-Nrf2/NF-kappaB signaling pathways. AB - Pogostone, a major component of Pogostemon cablin, has been demonstrated to possess antibacterial, anti-fungal, immunosuppressive and anti-inflammatory properties. To investigate the potential therapeutic effect of pogostone on lipopolysaccharide (LPS)-induced acute lung injury (ALI), mice were pretreated with pogostone prior to LPS exposure. After LPS challenge, the lungs were excised and the histological changes, wet to dry weight ratios, MPO activity reflecting neutrophil infiltration, and MDA activity reflecting oxidative stress were examined. The inflammatory cytokines in the BALF were determined by ELISA assay. Moreover, the expressions of p65 and phosphorylated p65 subunit of NF-kappaB, and Nrf2 in the nucleus in lung tissues were measured by Western blot analysis, and meanwhile the dependent genes of NF-kappaB and Nrf2 were assessed by RT-qPCR. The results showed that pretreatment with pogostone markedly improved survival rate, attenuated the histological alterations in the lung, reduced the MPO and MDA levels, decreased the wet/dry weight ratio of lungs, down-regulated the level of pro-inflammatory mediators including TNF-a, IL-1beta and IL-6. Furthermore, pretreatment with pogostone enhanced the Nrf2 dependent genes including NQO-1, GCLC and HO-1 but suppressed NF-kappaB regulated genes including TNF-alpha, IL 1beta and IL-6. The mechanism behind the protective effect was correlated with its regulation on the balance between Keap1-Nrf2 and NF-kappaB signaling pathways. Therefore, pogostone may be considered as a potential therapeutic agent for preventing and treating ALI. PMID- 26800100 TI - Effects of Traumatic Amputation on beta-Trace Protein and beta2-Microglobulin Concentrations in Male Soldiers. AB - BACKGROUND: Serum creatinine (SCr) levels are decreased following traumatic amputation, leading to the overestimation of glomerular filtration rate (GFR). beta-Trace protein (BTP) and beta2-microglobulin (B2M) strongly correlate with measured GFR and have not been studied following amputation. We hypothesized that BTP and B2M would be unaffected by traumatic amputation. METHODS: We used the Department of Defense Serum Repository to compare pre- and post-traumatic amputation serum BTP and B2M levels in 33 male soldiers, via the N Latex BTP and B2M nephelometric assays (Siemens Diagnostics, Tarrytown, N.Y., USA). Osterkamp estimation using DEXA scan measurements was used to establish percent estimated body weight loss (%EBWL). Results were analyzed for small (3-5.9% EBWL), medium (6-13.5%), and large (>13.5%) amputation subgroups; and for a control group matched 1:1 to the 12 large amputation subjects. Paired Student's t test was used for comparisons. RESULTS: Mean serum BTP levels were unchanged in controls, all amputees, and the small and medium amputation subgroups. BTP appeared to decrease following large %EBWL amputation (p = 0.05). Mean serum B2M levels were unchanged in controls, all amputees, and the small and medium amputation subgroups. B2M appeared to increase following large %EBWL amputation (p = 0.05). CONCLUSIONS: BTP and B2M levels are less affected than SCr by amputation, and should be considered for future study of GFR estimation. BTP and B2M changes following large %EBWL amputation require validation and may offer insight into non-GFR BTP and B2M determinants as well as increased cardiovascular disease and mortality following amputation. PMID- 26800099 TI - The role of negative selection in protein evolution revealed through the energetics of the native state ensemble. AB - Knowing the determinants of conformational specificity is essential for understanding protein structure, stability, and fold evolution. To address this issue, a novel statistical measure of energetic compatibility between sequence and structure was developed using an experimentally validated model of the energetics of the native state ensemble. This approach successfully matched sequences from a diverse subset of the human proteome to their respective folds. Unexpectedly, significant energetic compatibility between ostensibly unrelated sequences and structures was also observed. Interrogation of these matches revealed a general framework for understanding the origins of conformational specificity within a proteome: specificity is a complex function of both the ability of a sequence to adopt folds other than the native, and ability of a fold to accommodate sequences other than the native. The regional variation in energetic compatibility indicates that the compatibility is dominated by incompatibility of sequence for alternative fold segments, suggesting that evolution of protein sequences has involved substantial negative selection, with certain segments serving as "gatekeepers" that presumably prevent alternative structures. Beyond these global trends, a size dependence exists in the degree to which the energetic compatibility is determined from negative selection, with smaller proteins displaying more negative selection. This partially explains how short sequences can adopt unique folds, despite the higher probability in shorter proteins for small numbers of mutations to increase compatibility with other folds. In providing evolutionary ground rules for the thermodynamic relationship between sequence and fold, this framework imparts valuable insight for rational design of unique folds or fold switches. PMID- 26800103 TI - Traceability and Risk Analysis Strategies for Addressing Counterfeit Electronics in Supply Chains for Complex Systems. AB - Within the microelectronics industry, there is a growing concern regarding the introduction of counterfeit electronic parts into the supply chain. Even though this problem is widespread, there have been limited attempts to implement risk based approaches for testing and supply chain management. Supply chain risk management tends to focus on the highly visible disruptions of the supply chain instead of the covert entrance of counterfeits; thus counterfeit risk is difficult to mitigate. This article provides an overview of the complexities of the electronics supply chain, and highlights some gaps in risk assessment practices. In particular, this article calls for enhanced traceability capabilities to track and trace parts at risk through various stages of the supply chain. Placing the focus on risk-informed decision making through the following strategies is needed, including prioritization of high-risk parts, moving beyond certificates of conformance, incentivizing best supply chain management practices, adoption of industry standards, and design and management for supply chain resilience. PMID- 26800104 TI - Effect of spice-incorporated starch edible film wrapping on shelf life of white shrimps stored at different temperatures. AB - BACKGROUND: White shrimps (Litopenaeus vannamei) are a major aquaculture product in the world fishery market. The main aim of this study was to investigate the effect of clove- and cinnamon-assimilated starch edible films on the shelf life of white shrimps in terms of maintaining their freshness and other organoleptic properties. Physical, chemical, microbial and sensory qualities of edible film wrapped white shrimps were studied until they reached their limit of acceptability during storage at different temperatures (10 and 4 degrees C). RESULTS: Shrimp samples wrapped with spice-assimilated edible films showed lower bacterial counts. Shelf life extension of edible film-wrapped white shrimps was estimated to be 14 and 12 days for storage at 10 and 4 degrees C respectively. Reduced lipid oxidation and release of nitrogen base compounds were noted for edible film-wrapped shrimp samples. Good consumer acceptance was noted for edible film-wrapped shrimp samples through sensory evaluation. CONCLUSION: The results of this study show that spice-fused edible films were effective in inhibiting the growth of microbial populations. Reductions in lipid oxidation and total volatile base nitrogen were also achieved through edible film wrapping of shrimps, which increased their consumer acceptance during sensory evaluation. (c) 2016 Society of Chemical Industry. PMID- 26800105 TI - The fortuitous diagnosis of Burkitt lymphoma in a patient with chronic myelomonocytic leukemia. PMID- 26800106 TI - Oral alitretinoin treatment in patients with palmoplantar pustulosis inadequately responding to standard topical treatment: a randomized phase II study. AB - BACKGROUND: Palmoplantar pustulosis (PPP) is an inflammatory, debilitating skin disease. Topical drugs and systemic immunosuppressive agents are often ineffective. Previous uncontrolled studies have suggested that alitretinoin could be a meaningful treatment option for PPP. OBJECTIVES: The primary objective was to determine response to alitretinoin for the treatment of PPP based on the Palmoplantar Pustulosis Area and Severity Index (PPPASI) after 24 weeks of treatment. METHODS: A phase II, randomized, double-blind, placebo-controlled, multicentre study. Adult patients with PPP (with or without psoriasis) refractory to topical therapy and standard skin care were randomized 2:1 to alitretinoin 30 mg once daily or placebo for up to 24 weeks. The primary end point was PPPASI at week 24 (or the last visit in case of early withdrawal). Secondary end points included: percentage change from baseline in the modified Psoriasis Area and Severity Index (mPASI); percentage of patients with >= 50% or 75% improvement in PPPASI or mPASI scores from baseline; change in pustule count on the palms and soles; change in the Nail Psoriasis Severity Index and safety and tolerability assessments. RESULTS: Thirty-three patients were randomized: 24 patients to alitretinoin 30 mg and nine to placebo. Overall, there were no significant differences between alitretinoin 30 mg and placebo for any end point. The safety profile was consistent with that seen in patients with chronic severe hand eczema refractory to potent topical corticosteroids. CONCLUSIONS: Although the results were unexpected based on previous studies of alitretinoin in the treatment of PPP, this study provided no evidence to support further exploration of alitretinoin in the treatment of severe PPP. PMID- 26800107 TI - Breastfeeding: Beyond Nutrition. Breastfeeding Support: Beyond Biology. PMID- 26800108 TI - Important Transitions in Our Global, Multispeciality Organization. PMID- 26800110 TI - Letter to the editor with regard to the article entitled "Flow cytometric analysis of CD200 expression by pulmonary small cell carcinoma". PMID- 26800111 TI - In Vivo RNAi Efficacy of Palmitic Acid-Conjugated Dicer-Substrate siRNA in a Subcutaneous Tumor Mouse Model. AB - Short interfering RNAs are used in RNA interference technology and are powerful tools for target gene silencing in a sequence-specific manner. In this study, we synthesized Dicer-substrate siRNAs consisting of 27-nt double-stranded RNAs conjugated with palmitic acid at the 5'-end of the sense strand and investigated their RNA interference efficacies in vitro and in vivo. The palmitic acid conjugated 27-nt DsiRNAs (C16-Dsi27RNAs) were prepared by our simple synthesis strategy and achieved a good yield. C16-Dsi27RNAs showed enhanced in vitro RNA interference potency compared with not only non-modified Dsi27RNAs but also cholesterol-conjugated Dsi27RNAs against both an exogenous enhanced green fluorescent protein and the endogenous vascular endothelial growth factor gene in a human scirrhous-type gastric cancer cell line that stably expressed the enhanced green fluorescent protein gene (GCIY-eGFP). Additionally, C16-Dsi27RNAs had potent gene silencing activity against both enhanced green fluorescent protein and vascular endothelial growth factor as target genes in a subcutaneous tumor mouse model generated from GCIY-eGFP cells administered by intratumoral injection. These results suggest that the C16-Dsi27RNAs will be useful next generation RNA interference molecules that can overcome the problems associated with RNA interference technology. PMID- 26800112 TI - Gal-3 does not suppress cisplatin-induced apoptosis in A-375 melanoma cells. AB - Melanoma is the most aggressive of all skin cancers and is exceptionally resistant to therapies. During melanoma progression, cancer cells reprogram their proliferation and survival pathways and achieve resistance to treatment-induced apoptosis. Galectin-3 (gal-3) is a member of the lectin family and is involved in such biological processes as cell adhesion, growth and differentiation, the cell cycle, and apoptosis. Gal-3 also plays an important role in tumor development and metastasis. The relationship between gal-3 expression and these processes is specific to the tumor type and the stage of cancer progression. The biological functions of gal-3 depend on its localization in the cell. In the present study, human metastatic melanoma A-375 cells, characterized by weak endogenous expression of gal-3, were transfected with gal-3 cDNA and cisplatin-induced apoptosis was measured. Data from AnnexinV and mitochondrial membrane potential analysis revealed that gal-3 did not protect the A-375 melanoma cells against cisplatin. This result probably is associated with its nuclear localization in the cells. PMID- 26800114 TI - High-Resolution and High-Throughput Plasmonic Photopatterning of Complex Molecular Orientations in Liquid Crystals. AB - A plasmonic photopatterning technique is proposed and demonstrated for aligning the molecular orientation in liquid crystals (LCs) in patterns with designer complexity. Using plasmonic metamasks in which target molecular directors are encoded, LC alignments of arbitrary planar patterns can be achieved in a repeatable and scalable fashion withunprecedentedly high spatial resolution and high throughput. PMID- 26800115 TI - Ultra-short version of the oral health impact profile in elderly Chileans. AB - AIM: The aim of the present study was to develop and validate an ultra-short Spanish version of the Oral Health Impact Profile (OHIP) in an elderly Chilean population. METHODS: The OHIP-49Sp was applied to 490 older adults, and the seven questions with the higher impact on oral health-related quality of life were selected through linear regression. These items were applied to 85 older adults to test internal consistency (Cronbach's alpha). A discriminative validity analysis was carried out along with the assessment of sociodemographic and clinical variables. Data were analyzed using the Mann-Whitney U-test, Student's t test and one-way anova tests with a 95% confidence level. RESULTS: High internal consistency values were obtained for the OHIP-7Sp instrument (0.93). There was an association between the OHIP-7Sp scores and the presence of caries, need for complex periodontal treatment, prosthetic needs, and age younger than 70 years. CONCLUSION: The OHIP-7Sp proved to be a consistent and valid tool to assess oral health-related quality of life in Chilean older adults, and can be incorporated in epidemiological studies that include several other targets. Geriatr Gerontol Int 2017; 17: 277-285. PMID- 26800116 TI - Merging Chiral Bronsted Acid/Base Catalysis: An Enantioselective [4 + 2] Cycloaddition of o-Hydroxystyrenes with Azlactones. AB - An enantioselective [4 + 2] cycloaddition of o-hydroxylstyrenes with azlactones has been established by merging chiral Bronsted acid (chiral phosphoric acid) and base (chiral guanidine) catalysis, which constructed a biologically important dihydrocoumarin scaffold in an efficient and enantioselective style (up to 99% yield, 96:4 er). This approach has not only realized the successful application of o-hydroxylstyrenes as oxa-diene precursors in catalytic asymmetric cycloadditions but also established a new cooperative catalytic system of chiral phosphoric acid and chiral guanidine. PMID- 26800117 TI - Rearing conditions affected responses of weaned pigs to organic acids showing a positive effect on digestibility, microflora and immunity. AB - Three experiments were conducted to assess the response of weaned pigs to organic acid SF3, which contains 34% calcium formate, 16% calcium lactate, 7% citric acid and 13% medium chain fatty acids. Dietary treatments had no effect on growth performance of piglets (21-day weaning) fed the commercial prestart diet for 1 week before receiving the experimental diets supplemented with SF3 at 0, 3 or 5 g/kg diet (Exp. 1), whereas diarrhea frequency averaged across a week was decreased by SF3 supplementation (5 g/kg diet) in piglets fed the experimental diets immediately after weaning (Exp. 2). In Exp. 3, piglets (28-day weaning) were fed the control (containing pure colistin sulfate and enramycin, respectively, at 20 mg/kg diet) for 1 week and then were fed the control or SF3 supplemented (5 g/kg diet) diet for 2 weeks. The SF3-fed piglets had greater apparent ileal digestibility of calcium and dry matter, while also demonstrating greater overall gross energy, up-regulated jejunal expression of sodium-glucose cotransporter-1 and transforming growth factor-beta, down-regulated jejunal expression of tumor necrosis factor (TNF)-alpha, higher ileal Lactobacillus, with lower total bacteria content, lower plasma TNF-alpha but higher IgG levels than the control-fed piglets. Collectively, SF3 consumption improved diarrhea resistance of weaned pigs by improving nutrient digestibility, piglet immunity and intestinal bacteria profile. (c) 2016 Japanese Society of Animal Science. PMID- 26800119 TI - Emoticon-Based Ambivalent Expression: A Hidden Indicator for Unusual Behaviors in Weibo. AB - Recent decades have witnessed online social media being a big-data window for testifying conventional social theories quantitatively and exploring much detailed human behavioral patterns. In this paper, by tracing the emoticon use in Weibo, a group of hidden "ambivalent users" are disclosed for frequently posting ambivalent tweets containing both positive and negative emotions. Further investigation reveals that this ambivalent expression could be a novel indicator of many unusual social behaviors. For instance, ambivalent users with the female as the majority like to make a sound in midnights and at weekends. They mention their close friends frequently in ambivalent tweets, which attract more replies and serve as a more private communication way. Ambivalent users also respond differently to public affairs from others and demonstrate more interests in entertainment and sports events. Moreover, the sentiment shift in ambivalent tweets is more evident than usual and exhibits a clear "negative to positive" pattern. The above observations, though being promiscuous seemingly, actually point to the self-regulation of negative mood in Weibo, which could find its basis from the traditional emotion management theories in sociology but makes an important extension to the online environment in this study. Finally, as an interesting corollary, ambivalent users are found connected with compulsive buyers and turn out to be perfect targets for online marketing. PMID- 26800118 TI - Abundant cytomegalovirus (CMV) reactive clonotypes in the CD8(+) T cell receptor alpha repertoire following allogeneic transplantation. AB - Allogeneic stem cell transplantation is potentially curative, but associated with post-transplantation complications, including cytomegalovirus (CMV) infections. An effective immune response requires T cells recognizing CMV epitopes via their T cell receptors (TCRs). Little is known about the TCR repertoire, in particular the TCR-alpha repertoire and its clinical relevance in patients following stem cell transplantation. Using next-generation sequencing we examined the TCR-alpha repertoire of CD8(+) T cells and CMV-specific CD8(+) T cells in four patients. Additionally, we performed single-cell TCR-alphabeta sequencing of CMV-specific CD8(+) T cells. The TCR-alpha composition of human leucocyte antigen (HLA)-A*0201 CMVpp65- and CMVIE -specific T cells was oligoclonal and defined by few dominant clonotypes. Frequencies of single clonotypes reached up to 11% of all CD8(+) T cells and half of the total CD8(+) T cell repertoire was dominated by few CMV reactive clonotypes. Some TCR-alpha clonotypes were shared between patients. Gene expression of the circulating CMV-specific CD8(+) T cells was consistent with chronically activated effector memory T cells. The CD8(+) T cell response to CMV reactivation resulted in an expansion of a few TCR-alpha clonotypes to dominate the CD8(+) repertoires. These results warrant further larger studies to define the ability of oligoclonally expanded T cell clones to achieve an effective anti viral T cell response in this setting. PMID- 26800120 TI - Measurement of Elastic Modulus of Collagen Type I Single Fiber. AB - Collagen fibers are the main components of the extra cellular matrix and the primary contributors to the mechanical properties of tissues. Here we report a novel approach to measure the longitudinal component of the elastic moduli of biological fibers under conditions close to those found in vivo and apply it to type I collagen from rat tail tendon. This approach combines optical tweezers, atomic force microscopy, and exploits Euler-Bernoulli elasticity theory for data analysis. This approach also avoids drying for measurements or visualization, since samples are freshly extracted. Importantly, strains are kept below 0.5%, which appear consistent with the linear elastic regime. We find, surprisingly, that the longitudinal elastic modulus of type I collagen cannot be represented by a single quantity but rather is a distribution that is broader than the uncertainty of our experimental technique. The longitudinal component of the single-fiber elastic modulus is between 100 MPa and 360 MPa for samples extracted from different rats and/or different parts of a single tail. Variations are also observed in the fibril-bundle/fibril diameter with an average of 325+/-40 nm. Since bending forces depend on the diameter to the fourth power, this variation in diameter is important for estimating the range of elastic moduli. The remaining variations in the modulus may be due to differences in composition of the fibril-bundles, or the extent of the proteoglycans constituting fibril bundles, or that some single fibrils may be of fibril-bundle size. PMID- 26800121 TI - Erwinia teleogrylli sp. nov., a Bacterial Isolate Associated with a Chinese Cricket. AB - A bacterial isolate (SCU-B244T) was obtained in China from crickets (Teleogryllus occipitalis) living in cropland deserted for approximately 10 years. The isolated bacteria were Gram-negative, facultatively anaerobic, oxidase-negative rods. A preliminary analysis of the 16S rRNA gene sequence indicated that the strain belongs to either the genus Erwinia or Pantoea. Analysis of multilocus sequence typing based on concatenated partial atpD, gyrB and infB gene sequences and physiological and biochemical characteristics indicated that the strain belonged to the genus Erwinia, as member of a new species as it was distinct from other known Erwinia species. Further analysis of the 16S rRNA gene showed SCU-B244T to have 94.71% identity to the closest species of that genus, Erwinia oleae (DSM 23398T), which is below the threshold of 97% used to discriminate bacterial species. DNA-DNA hybridization results (5.78+/-2.52%) between SCU-B244T and Erwinia oleae (DSM 23398T) confirmed that SCU-B244T and Erwinia oleae (DSM 23398T) represent different species combined with average nucleotide identity values which range from 72.42% to 74.41. The DNA G+C content of SCU-B244T was 55.32 mol%, which also differs from that of Erwinia oleae (54.7 to 54.9 mol%). The polyphasic taxonomic approach used here confirmed that the strain belongs to the Erwinia group and represents a novel species. The name Erwinia teleogrylli sp. nov. is proposed for this novel taxon, for which the type strain is SCU-B244T (= CGMCC 1.12772T = DSM 28222T = KCTC 42022T). PMID- 26800122 TI - Nonlinear Saturable Absorption of Liquid-Exfoliated Molybdenum/Tungsten Ditelluride Nanosheets. AB - Molybdenum disulfide (MoS2 ) and tungsten disulfide (WS2 ), two representative transition metal dichalcogenide materials, have captured tremendous interest for their unique electronic, optical, and chemical properties. Compared with MoS2 and WS2 , molybdenum ditelluride (MoTe2 ) and tungsten ditelluride (WTe2 ) possess similar lattice structures while having smaller bandgaps (less than 1 eV), which is particularly interesting for applications in the near-infrared wavelength regime. Here, few-layer MoTe2 /WTe2 nanosheets are fabricated by a liquid exfoliation method using sodium deoxycholate bile salt as surfactant, and the nonlinear optical properties of the nanosheets are investigated. The results demonstrate that MoTe2 /WTe2 nanosheets exhibit nonlinear saturable absorption property at 1.55 MUm. Soliton mode-locking operations are realized separately in erbium-doped fiber lasers utilizing two types of MoTe2 /WTe2 -based saturable absorbers, one of which is prepared by depositing the nanosheets on side polished fibers, while the other is fabricated by mixing the nanosheets with polyvinyl alcohol and then evaporating them on substrates. Numerous applications may benefit from the nonlinear saturable absorption features of MoTe2 /WTe2 nanosheets, such as visible/near-infrared pulsed laser, materials processing, optical sensors, and modulators. PMID- 26800124 TI - Round cell sarcoma with CIC-DUX4 gene fusion: Discussion of the distinctive cytomorphologic, immunohistochemical, and molecular features in the differential diagnosis of round cell tumors. AB - BACKGROUND: Undifferentiated round cell sarcomas are a heterogeneous group, and include tumors that resemble the Ewing sarcoma family. Although a subset defined by recurrent CIC-DUX4 gene fusion has been recently characterized, data regarding the cytomorphologic features are currently limited. Two recent fine-needle aspiration (FNA) cases prompted review of the spectrum of round cell tumors in the differential diagnosis to determine distinctive diagnostic features. METHODS: Two genetically confirmed FNA cases were identified. Cytomorphologic features were evaluated on FNA smears and hematoxylin and eosin-stained cell block and concurrent needle biopsy sections, and immunohistochemical studies performed on cell block and biopsy sections were reviewed. RESULTS: The 2 patients were a 24 year-old man with a posterior mediastinal mass and a 69-year-old woman with a gluteal mass. FNA smears were cellular with tumor cells present in large groups and singly dispersed. Tumor cells had large, round-to-ovoid, hyperchromatic nuclei with irregular membranes, frequent large nucleoli, and a moderate amount of vacuolated cytoplasm. Both cases demonstrated necrosis, and one case had prominent myxoid stroma. Immunohistochemistry demonstrated focal-to-multifocal CD99 positivity and diffuse nuclear staining for WT1; staining for cytokeratin, desmin, S-100, CD34, CD45, and TdT were negative. Fluorescence in situ hybridization demonstrated CIC-DUX4 fusion in both cases. CONCLUSIONS: CIC-DUX4 round cell sarcoma differs from Ewing sarcoma in that it has more atypical cytologic features and lacks the diffuse membranous CD99 staining pattern characteristic of Ewing sarcoma. The differential diagnosis is broad, and requires the judicious use of ancillary studies. Focal-to-multifocal CD99 immunoreactivity and diffuse nuclear WT1 positivity is characteristic of CIC-DUX4 sarcoma, and should prompt molecular testing. Cancer Cytopathol 2016;124:350-61. (c) 2016 American Cancer Society. PMID- 26800125 TI - REPLY: A multi-artery fractional flow reserve (FFR) approach for handling coronary stenosis-stenosis interaction in the multi-vessel disease (MVD) arena. PMID- 26800126 TI - Epinephrine administration and Takotsubo syndrome: Lessons from past experiences. PMID- 26800127 TI - Physical activity and peripheral arterial disease among patients with coronary artery disease or congestive heart failure. PMID- 26800128 TI - Kounis syndrome induced by cefditoren pivoxil. PMID- 26800129 TI - Chagas heart disease in professional athletes from endemic countries: A notorious case calls attention for its identification and stratification. PMID- 26800130 TI - Effects of probucol on left atrial remodeling in patients with paroxysmal atrial fibrillation. PMID- 26800131 TI - Short-term catheter based treatment of aortic regurgitation by Edwards' Sapien 3 valve-in-valve implantation because of a poorly placed Medtronic CoreValve. PMID- 26800132 TI - Valve thrombosis 3years after transcatheter aortic valve implantation. PMID- 26800133 TI - Registries for health technology assessment: Back to the future. PMID- 26800134 TI - Reply to a comment concerning "Rare form of basal ballooning without reduction of left ventricular function in takotsubo cardiomyopathy". PMID- 26800135 TI - The challenge for predicting bleeding events by assessing platelet reactivity following coronary stenting. AB - BACKGROUND: Predicting future bleeding events represents an unmet medical need that will ultimately improve outcomes during dual antiplatelet therapy (DAPT). Although low platelet reactivity (LPR) may be linked to bleeding, standardized and clinically validated threshold for reliable DAPT bleeding risk stratification is lacking. We sought to define the predictive value of LPR for future bleeding events in a large cohort of post-stenting single-center Korean patients. METHODS: Consecutive patients (n=800) who underwent coronary interventions with drug eluting stents were enrolled from March 2010 to October 2014. Among them, 699 (80%) were treated with 75mg/daily clopidogrel, 93 (19%) with 10mg/daily prasugrel, and 8 (1%) with 180mg/daily ticagrelor, all on top of 100mg/daily aspirin. Bleeding was assessed by BARC 2-5 scale, and events were collected for 1 year post stenting. Platelet reactivity on DAPT was measured by the VerifyNow P2Y12 assay at 1month following coronary intervention. RESULTS: There were a total of 18 (2.1%) bleeding events. The LPR value defined as <=139 PRU (AUC: 0.867, p<0.0001) was an independent predictor for bleeding (HR=21.26, 95% CI: 6.19-73.0, p<0.0001) by univariate analysis, and remains significant (HR=11.49; 95% CI: 2.89-45.67, p<0.0004) following multivariate analysis adjustment. However, the specificity (81.7%) and sensitivity (83.3%) of the test was low challenging the assay utility to predict bleeding. CONCLUSION: Despite being an independent predictor for bleeding, LPR failed to reliably triage such patients due to low specificity and sensitivity of the test. There is an urgent need for a randomized trial with uniformed DAPT regimen, bleeding definition, and careful follow-up. PMID- 26800136 TI - Pheochromocytoma, paraganglioma, Takotsubo syndrome (acute and "chronic"), and catecholamine cardiomyopathies. PMID- 26800137 TI - Cardiogenic shock secondary to methamphetamine induced cardiomyopathy requiring veno-arterial extra-corporeal membrane oxygenation. PMID- 26800138 TI - Atrial fibrillation and D dimer levels for patients with acute decompensated heart failure. PMID- 26800139 TI - Prior myocardial infarction is associated with coronary endothelial dysfunction in women with signs and symptoms of ischemia and no obstructive coronary artery disease. PMID- 26800140 TI - Clinical development plan for regenerative therapy in heart failure. PMID- 26800141 TI - The use of substituted alkynyl phenoxy derivatives of piperonyl butoxide to control insecticide-resistant pests. AB - BACKGROUND: Derivatives of piperonyl butoxide with alkynyl side chains were tested in vitro and in vivo against pyrethroid-resistant Meligethes aeneus and imidacloprid-resistant Myzus persicae. RESULTS: Synergists with the alkynyl side chain were more effective inhibitors of P450 activity in vitro than piperonyl butoxide, and demonstrated high levels of synergism in vivo, with up to 290-fold synergism of imidacloprid against imidacloprid-resistant M. persicae. CONCLUSIONS: These 'second-generation' synergists could overcome metabolic resistance in many pest species and possibly enable reduced rates of insecticide application in some cases. (c) 2016 Society of Chemical Industry. PMID- 26800142 TI - Paravaginal defect: A new classification of fascial and muscle tears in the paravaginal region. AB - The lateral support of the vaginal wall depends on the integrity of the paravaginal section of the visceral pelvic fascia, levator ani, and their connection. Various defects of the muscle and fascia can result in identical clinical findings-ie, the descent of the lateral vaginal sulcus. In this study, we created a realistic scheme for classifying paravaginal defects, based on the complex relationship of the pelvic fascia with the levator ani. Surgical observations, cadaver examinations, and a complex magnetic resonance imaging (MRI)-based 3-dimensional (3D) model were used to analyze the spatial relationships of normal and defective anatomy of the female pelvic floor. Descent of the lateral vaginal sulcus can result from a defect in the paravaginal visceral pelvic fascia, levator ani, or both. The fascial defect can be partial or complete, and the muscle defect can vary in location. A detailed illustrated classification is presented. We present a new model of the pathology that underlies a common clinical finding. PMID- 26800143 TI - Some New Observations on Activation Energy of Crystal Growth for Thermally Activated Crystallization. AB - Calorimetric study of glass/crystal phase transformation in disordered semiconductors is a significant tool for understanding their crystallization kinetics. Such studies provide the basis for practical application of glasses. Differential scanning calorimetry (DSC) is one of the advanced techniques for the analysis of thermally induced crystallization in glassy or amorphous systems. We are reporting the nonisothermal DSC measurements on four amorphous systems of Se70Te30 alloy with Ag, Cd, Sb, and Zn as chemical modifiers. In general, the rate constant (K) shows Arrhenian dependence on temperature (T), i.e., K = K0 exp (-Eg/RT) where Eg is the activation energy of crystal growth and K0 is called the pre-exponential factor of rate constant. In the present work, an experiment is designed to see the effect of composition on the activation energy of crystal growth. We have found Meyer-Neldel relation (MNR) between Eg and K0 for present systems. Another interesting feature of present work is the observation of further relation between Meyer-Neldel prefactor and Meyer-Neldel energy. PMID- 26800145 TI - A high frequency of allopolyploid speciation in the gymnospermous genus Ephedra and its possible association with some biological and ecological features. AB - The origin and evolution of polyploids have been studied extensively in angiosperms and ferns but very rarely in gymnosperms. With the exception of three species of conifers, all natural polyploid species of gymnosperms belong to Ephedra, in which more than half of the species show polyploid cytotypes. Here, we investigated the origin and evolution of polyploids of Ephedra distributed in the Qinghai-Tibetan Plateau (QTP) and neighbouring areas. Flow cytometry (FCM) was used to measure the ploidy levels of the sampled species that are represented by multiple individuals from different populations, and then, two single-copy nuclear genes (LFY and DDB2) and two chloroplast DNA fragments were used to unravel the possible origins and maternal donors of the polyploids. The results indicate that the studied polyploid species are allopolyploids, and suggest that allotetraploidy is a dominant mode of speciation in Ephedra. The high percentage of polyploids in the genus could be related to some of its biological attributes such as vegetative propagation, a relatively high rate of unreduced gamete formation, and a small genome size relative to most other gymnosperms. Significant ecological divergences between allotetraploids and their putative progenitors were detected by PCAs and anova and Tukey's tests, with the exception of E. saxatilis. The overlap of geographical distributions and ecological niches of some diploid species could have provided opportunities for interspecific hybridization and allopolyploid speciation. PMID- 26800146 TI - Cytologic diagnosis of coccidioidomycosis: Spectrum of findings in Southern Arizona patients over a 10 year period. AB - BACKGROUND: The largest series examining the cytological diagnosis of coccidioidomycosis was reported more than 20 years ago and only considered fine needle aspiration (FNA) specimens from pulmonary nodules. Since then, there has been a substantial increase in the incidence of the disease in endemic regions. The aims of this study were to examine the spectrum of Coccidioides in all cytologic specimens and detail their diagnostic and clinical features. The prevalence of infection is also examined against temperature and precipitation data. METHODS: The Department of Pathology database was retrospectively searched for cases diagnosed as coccidioidomycosis. Climate report was obtained from National Weather Service Forecast Office. Statistical analysis was carried out using JMP version 11.2.0. RESULTS: The presence of Coccidiodes was microscopically diverse with immature spherules, variably sized spherules, endosporulating spherules, empty spherules, and ruptured spherules being observed. Bronchoalveolar lavages demonstrated the greatest number of different forms of Coccidioides and were associated with acute inflammatory response. Granulomas were rare and mostly seen in lymph nodes and extra pulmonary sites. A necrotic background with paucity of inflammation was frequently seen in lung FNA. Immune competent patients outnumbered immunocompromised patients, illustrating the importance of considering the diagnosis in all patients. The reported association between rainfall and peak prevalence was not observed in our study. CONCLUSION: Coccidioides has diverse cytological appearance and varied host response depending on the site and type of preparation examined. In endemic areas, the disease should be considered in all patients, independent of immune status, and throughout the year. PMID- 26800148 TI - Radiographic size of retroperitoneal lymph nodes predicts pathological nodal involvement for patients with renal cell carcinoma: development of a risk prediction model. AB - OBJECTIVES: To evaluate the ability of clinical and radiographic features to predict lymph node (pN1) disease among patients with renal cell carcinoma undergoing radical nephrectomy (RN), and to develop a preoperative risk prediction model. PATIENTS AND METHODS: In all, 220 patients with preoperative computed tomography scans available for review underwent RN with lymph node dissection (LND) from 2000 to 2010. Radiographic features were assessed by one genitourinary radiologist blinded to pN status. Associations of features with pN1 disease were evaluated using logistic regression to develop predictive models. Model performance was assessed using area under the receiver operating characteristic curve (AUC) and decision curve analysis. RESULTS: The median (interquartile range) lymph node yield was 10 (5-18). In all, 55 patients (25%) had pN1 disease at RN. On univariable analysis, the maximum lymph node (LN) short axis diameter [odds ratio (OR) 1.17; P < 0.001] predicted pN1 disease with an AUC of 0.84. Although several clinical and radiographic features were associated with pN1 disease, only two were retained in the multivariable model: maximum LN short axis diameter (OR 1.19; P <0.001) and radiographic perinephric/sinus fat invasion (OR 44.64; P = 0.01), with an AUC of 0.85. On decision curve analysis, the single variable and multivariable models showed similar net benefit. CONCLUSION: Two radiographic features, maximum LN short axis diameter and perinephric/sinus fat invasion, outperformed traditional clinical variables in predicting pN1 disease. Maximum LN short axis diameter alone showed excellent predictive performance, and, if validated externally, would provide for a simple model to guide patient selection for LND. PMID- 26800151 TI - Ruthenium-Catalyzed C-C Bond Cleavage of 2H-Azirines: A Formal [3+2+2] Cycloaddition to Fused Azepine Skeletons. AB - 2H-azirines can serve as three-atom synthons by C-C bond cleavage, however, it involves a high energy barrier under thermal conditions (>50.0 kcal mol(-1) ). Reported is a ruthenium-catalyzed [3+2+2] cycloaddition reaction of 2H-azirines with diynes, thus leading to the formation of fused azepine skeletons. This approach features an unprecedented metal-catalyzed C-C bond cleavage of 2H azirines at room temperature, and the challenging construction of aza-seven membered rings from diynes. The results of this study provide a new reaction pattern for constructing nitrogen-containing seven-membered rings and may find applications in the synthesis of other complex heterocycles. PMID- 26800153 TI - Seventeen year mortality in a cohort of patients attending opioid agonist treatment in Ireland. Commentary on 'methadone-maintained patients in primary care have higher rates of chronic disease' (O'Toole et al., European Journal of General Practice 2014;20:275-80). PMID- 26800152 TI - Selection of Reference Genes for Real-Time Quantitative PCR in Pinus massoniana Post Nematode Inoculation. AB - Pinus massoniaia Lamb has gained more and more attention as the most important tree species for timber and forestation in South China. Gene expression studies are of great importance to identify new and elite cultivars. Real-time quantitative PCR, a highly sensitive and specific method, is commonly used in the analysis of gene expression. The appropriate reference genes must be employed to normalize the calculation program for ascertaining repeatable and significant results. Herein, eleven housekeeping genes were evaluated during different stages of P. massoniana post nematode inoculation in this study. Three statistical approaches such as geNorm, NormFinder and BestKeeper were selected to analyze the stability of candidate genes. The results indicated that U2af and beta-TUB were the most stable reference genes. These two genes could be used for the normalization in most of the experiments of P. massoniana, while Histone and AK were the least stable ones. In addition, EF expressed at the lowest average Ct value was the most abundant candidate gene. As an important gene associated with defense mechanisms, ABC transporter was analyzed by qRT-PCR, and the results were used to confirm the reliability of two genes. The selected reference genes in the present study will be conducive to future gene expression normalized by qRT-PCR in P. massoniana. PMID- 26800154 TI - Deep Impact: Effects of Mountaintop Mining on Surface Topography, Bedrock Structure, and Downstream Waters. AB - Land use impacts are commonly quantified and compared using 2D maps, limiting the scale of their reported impacts to surface area estimates. Yet, nearly all land use involves disturbances below the land surface. Incorporating this third dimension into our estimates of land use impact is especially important when examining the impacts of mining. Mountaintop mining is the most common form of coal mining in the Central Appalachian ecoregion. Previous estimates suggest that active, reclaimed, or abandoned mountaintop mines cover ~7% of Central Appalachia. While this is double the areal extent of development in the ecoregion (estimated to occupy <3% of the land area), the impacts are far more extensive than areal estimates alone can convey as the impacts of mines extend 10s to 100s of meters below the current land surface. Here, we provide the first estimates for the total volumetric and topographic disturbance associated with mining in an 11 500 km(2) region of southern West Virginia. We find that the cutting of ridges and filling of valleys has lowered the median slope of mined landscapes in the region by nearly 10 degrees while increasing their average elevation by 3 m as a result of expansive valley filling. We estimate that in southern West Virginia, more than 6.4km(3) of bedrock has been broken apart and deposited into 1544 headwater valley fills. We used NPDES monitoring datatsets available for 91 of these valley fills to explore whether fill characteristics could explain variation in the pH or selenium concentrations reported for streams draining these fills. We found that the volume of overburden in individual valley fills correlates with stream pH and selenium concentration, and suggest that a three dimensional assessment of mountaintop mining impacts is necessary to predict both the severity and the longevity of the resulting environmental impacts. PMID- 26800156 TI - The Prevalence of Cigarette Smoking Among Rural-to-Urban Migrants in China: A Systematic Review and Meta-Analysis. AB - BACKGROUND: The increasing rural-to-urban migrant population in China may be linked to the susceptibility to tobacco use. We aimed to investigate the prevalence of smoking among rural-to-urban migrants in China. METHODS: Major English and Chinese databases were searched for original studies on smoking prevalence among rural-to-urban migrants in China. A validated quality assessment tool was used to evaluate these studies. Subsequently, data were extracted to calculate the overall pooled estimate of prevalence using random effect model, and then stratified by gender, definition, location, and occupation. Meta regression analysis was used to identify the source of heterogeneity among variables. RESULTS: We identified 17 eligible studies involving 32,694 migrants. The overall pooled prevalence estimate of smoking among rural-to-urban migrants was 27.25% (95% CI: 23.34, 31.34), with significant heterogeneity (I(2) = 98.2, p < .01). In stratified analysis, specific pooled prevalence estimates were 46.71% for male (95% CI: 40.51, 52.97) and 5.34% for female (95% CI: 2.90, 8.45); 26.71% (95% CI: 17.00, 37.71), and 24.96% (95% CI: 18.65, 31.86) in current and daily smoking group, respectively; 21.89% (95% CI: 15.80, 28.66) and 30.59% (95% CI: 20.04, 42.28) for migrants in North and South China, respectively; 48.34% (95% CI: 24.63, 72.46) in construction industry, 31.77% (95% CI: 15.54, 50.67) in manufacturing industry and 18.69% (95% CI: 11.37, 27.32) in service industry, respectively. Meta-regression analysis revealed that gender and occupation differences contributed to high heterogeneity. CONCLUSION: Cigarette smoking is still prevalent among rural-to-urban migrants, which may be influenced by gender and occupations. Policies should be designed and conducted to control smoking prevalence among these populations. PMID- 26800157 TI - Transfer of location-specific control to untrained locations. AB - Recent research highlights a seemingly flexible and automatic form of cognitive control that is triggered by potent contextual cues, as exemplified by the location-specific proportion congruence effect--reduced compatibility effects in locations associated with a high as compared to low likelihood of conflict. We investigated just how flexible location-specific control is by examining whether novel locations effectively cue control for congruency-unbiased stimuli. In two experiments, biased (mostly compatible or mostly incompatible) training stimuli appeared in distinct locations. During a final block, unbiased (50% compatible) stimuli appeared in novel untrained locations spatially linked to biased locations. The flanker compatibly effect was reduced for unbiased stimuli in novel locations linked to a mostly incompatible compared to a mostly compatible location, indicating transfer. Transfer was observed when stimuli appeared along a linear function (Experiment 1) or in rings of a bullseye (Experiment 2). The novel transfer effects imply that location-specific control is more flexible than previously reported and further counter the complex stimulus-response learning account of location-specific proportion congruence effects. We propose that the representation and retrieval of control settings in untrained locations may depend on environmental support and the presentation of stimuli in novel locations that fall within the same categories of space as trained locations. PMID- 26800159 TI - How amino and nitro substituents direct electrophilic aromatic substitution in benzene: an explanation with Kohn-Sham molecular orbital theory and Voronoi deformation density analysis. AB - The substituent effect of the amino and nitro groups on the electronic system of benzene has been investigated quantum chemically using quantitative Kohn-Sham molecular orbital theory and a corresponding energy decomposition analysis (EDA). The directionality of electrophilic substitution in aniline can accurately be explained with the amount of contribution of the 2pz orbitals on the unsubstituted carbon atoms to the highest occupied pi orbital. For nitrobenzene, the molecular pi orbitals cannot explain the regioselectivity of electrophilic substitution as there are two almost degenerate pi orbitals with nearly the same 2pz contributions on the unsubstituted carbon atoms. The Voronoi deformation density analysis has been applied to aniline and nitrobenzene to obtain an insight into the charge rearrangements due to the substituent. This analysis method identified the orbitals involved in the C-N bond formation of the pi system as the cause for the pi charge accumulation at the ortho and para positions in the case of the NH2 group and the largest charge depletion at these same positions for the NO2 substituent. Furthermore, we showed that it is the repulsive interaction between the piHOMO of the phenyl radical and the piHOMO of the NH2 radical that is responsible for pushing up the piHOMO of aniline and therefore activating this pi orbital of the phenyl ring towards electrophilic substitution. PMID- 26800160 TI - Efficacy of Alveolar Vertical Distraction Osteogenesis and Autogenous Bone Grafting for Dental Implants: Systematic Review and Meta-Analysis. AB - PURPOSE: The aim of this study was to assess the efficacy of alveolar vertical distraction osteogenesis and autogenous bone grafting in terms of bone gain, bone resorption, and implant survival and success rates and investigate the relationship between bone gain and resorption after alveolar vertical distraction osteogenesis. MATERIALS AND METHODS: A systematic search was done using MEDLINE, EMBASE, the Cochrane Library, and KoreaMed from inception to April 30, 2014. Supplementary manual searches of published full-text articles were also performed. RESULTS: Searches of four electronic databases and manual searches resulted in 1,538 articles. After selection, four studies were included in the systematic review and meta-analysis. The difference in bone gain at the end of distraction or bone grafting was statistically significant (weighted mean difference [WMD] 1.86, 95% CI 0.03 to 3.69, P = .05; heterogeneity: I(2) = 78%, P = .01). However, there was not a statistically significant difference between alveolar distraction osteogenesis and onlay bone grafting (WMD 0.30, 95% CI -0.99 to 1.59, P = .065). Bone resorption between the end of treatment and the time of implant placement was not statistically significant (WMD -0.12, 95% CI -1.10 to 0.85, P = .80; heterogeneity: I(2) = 78%, P = .01). A simple equation related to bone gain and resorption after alveolar vertical distraction was induced from these results. CONCLUSION: There was not a statistically significant difference between alveolar distraction osteogenesis and onlay bone grafting in terms of bone gain and bone resorption. PMID- 26800161 TI - A New Experimental Design for Bacterial Microleakage Investigation at the Implant Abutment Interface: An In Vitro Study. AB - PURPOSE: This study aimed to test bacterial microleakage at the implant-abutment interface (IAI) before and after dynamic loading using a new chewing simulation. MATERIALS AND METHODS: Fourteen implant systems (n = 5 samples of each) were divided into two groups: (1) systems with conical implant-abutment connections (IACs), and (2) systems with flat IACs. For collecting samples without abutment disconnection, channels (O = 0.3 mm) were drilled into implants perpendicularly to their axes, and stainless-steel cannulas were adhesively glued inside these channels to allow a sterilized rinsing solution to enter the implant interior and to exit with potential contaminants for testing. Implants were embedded in epoxy resin matrices, which were supported by titanium cylinders with lateral openings for inward and outward cannulas. Abutments were tightened and then provided with vertically adjustable, threaded titanium balls, which were cemented using composite cement. Specimens were immersed in a bacterial liquid and after a contact time of 15 minutes, the implant interior was rinsed prior to chewing simulation (0 N ? static seal testing). Specimens were exposed to a Frankfurt chewing simulator. Two hundred twenty force cycles per power level (110 in +/- X axis) were applied to simulate a daily masticatory load of 660 chewing cycles (equivalent to 1,200,000 cycles/5 years). The applied load was gradually increased from 0 N to a maximum load of 200 N in 25-N increments. The implant interior was rinsed to obtain samples before each new power level. All samples were tested using fluorescence microscopy; invading microorganisms could be counted and evaluated. RESULTS: No bacterial contamination was detected under static loading conditions in both groups. After loading, bacterial contamination was detected in one sample from one specimen in group 1 and in two samples from two specimens in group 2. CONCLUSION: Controlled dynamic loading applied in this study simulated a clinical situation and enabled time-dependent analysis regarding the bacterial seal of different implant systems. Conical IACs offer a better bacterial seal compared with flat IACs, which showed increased microleakage after dynamic loading. IAC design plays a crucial role in terms of bacterial colonization. Taking samples of the implant interior without abutment disconnection eliminates an error source. PMID- 26800162 TI - Assisted Wound Healing and Vertical Bone Regeneration with Simultaneous Implant Placement: A Histologic Pilot Study. AB - PURPOSE: To evaluate the effectiveness of platelet-rich fibrin (PRF) and freeze dried bone allograft (FDBA) in vertical bone augmentation with immediate implant placement using histologic analysis. MATERIALS AND METHODS: Six Merino sheep received a total of 36 Branemark MKIII implants; three implants were placed supracrestally in each tibia with vertical exposure of four threads. Each implant received one of the three grafting options (MinerOss + PRF or MinerOss or PRF). The grafting materials were covered with a resorbable collagen membrane (Mem-Lok 30 * 40 mm, BioHorizons). Animals were sacrificed at 4 and 8 weeks, respectively, and specimens were prepared and collected for histologic analysis. Ground sections and decalcified sections were prepared. RESULTS: The various stages of graft integration into native bone and the implant were observed at different time points, and comparison between the three grafting options was possible. Osteogenic potential with vertical generation of bone was observed in the three groups. At week 4, woven bone formation at the bone graft interface was observed; new bone did not appear to be organized at week 4. At week 8, the graft appeared to be fully replaced by vital mature and well-organized bone arranged in lamellae with osteocytes encapsulated within the bone. The vertical bone gain at 8 weeks was higher for the PRF + MinerOss group with viable bone extending above the first thread. Both the MinerOss and PRF groups had vertical bone gain extended to the second thread. CONCLUSION: MinerOss appeared to be effective in vertical bone augmentation with simultaneous implant placement. PRF enhanced vertical bone augmentation when combined with MinerOss. PMID- 26800163 TI - A Systematic Review on Immediate Loading of Implants Used to Support Overdentures Opposed by Conventional Prostheses: Factors That Might Influence Clinical Outcomes. AB - PURPOSE: Different treatment protocols in terms of number, diameter, and suprastructure design have been proposed for immediately loaded implants that are used to support mandibular overdentures opposed by maxillary conventional dentures. The aim of this study was to investigate the influence of these protocols on survival rates as well as clinical and prosthodontic outcomes. MATERIALS AND METHODS: Several electronic databases were searched for all relevant articles published from 1966 to June 2014. Only randomized controlled trials and prospective studies with a minimum follow-up of 12 months were selected. The primary outcomes of interest were the success and survival rates of the implants. Prosthodontic complications were also evaluated. RESULTS: Fourteen studies fulfilled the inclusion criteria. Of the studies identified, nine were randomized controlled trials and five were prospective studies. The mean follow up period was 3 years or less for the vast majority of the studies. The reported survival and success rates were comparable to that of conventional loading for most of the included studies. No specific immediate loading protocol seemed to perform better in terms of clinical and prosthodontic outcomes. CONCLUSION: Immediate loading protocols of mandibular overdentures seem to be a viable alternative to conventional loading. It was not possible to recommend a specific treatment protocol related to the number, diameter of the implants, and attachment system used. Long-term, well-designed studies comparing different immediate loading modalities could help to establish a protocol that delivers the most clinically predictable, efficient, and cost-effective outcome for edentulous patients in need of implant overdentures. PMID- 26800164 TI - Bone Generation Profiling Around Photofunctionalized Titanium Mesh. AB - PURPOSE: The aim of this study was to evaluate whether photofunctionalization of titanium mesh enhances its osteoconductive capability. MATERIALS AND METHODS: The titanium mesh (0.2 mm thickness) used in this study was made of commercially pure grade-2 titanium and had hexagonal apertures (2 mm width). Photofunctionalization was performed by treating titanium mesh with UV light for 12 minutes using a photo device immediately before use. Untreated or photofunctionalized titanium mesh was placed into rat femurs, and bone generation around titanium mesh was profiled using three-dimensional (3D) microcomputed tomography (micro-CT). A set of in vitro experiments was conducted using bone marrow-derived osteoblasts. RESULTS: Photofunctionalized titanium mesh surfaces were characterized by the regenerated hydrophilicity and significantly reduced surface carbon. Bone generation profiling at week 3 of healing showed that the hexagonal apertures in photofunctionalized mesh were 95% filled, but they were only 57% filled in untreated mesh, particularly with the center zone remaining as a gap. Bone profiling in slices parallel to the titanium surface showed that photofunctionalized titanium mesh achieved 90% bone occupancy 0 to 400 MUm from the surface, compared with only 35% for untreated mesh. Bone occupancy remained as high as 55% 800 to 1,200 MUm from photofunctionalized titanium mesh surfaces, compared with less than 20% for untreated mesh. In vitro, photofunctionalized titanium mesh expedited and enhanced attachment and spread of osteoblasts, and increased ALP activity and the rate of mineralization. CONCLUSION: This study may provide novel and advanced metrics describing the osteoconductive property of photofunctionalized titanium mesh. Specifically, photofunctionalization not only increased the breadth, but also the 3D range, of osteoconductivity of titanium mesh, enabling space-filling and far-reaching osteoconductivity. Further translational and clinical studies are warranted to establish photofunctionalized titanium mesh as a novel clinical tool for better bone regeneration and augmentation. PMID- 26800165 TI - Dimensional Changes Following Lateral Wall Sinus Augmentation Without Concomitant Implant Placement Using a Composite Bone Graft. AB - PURPOSE: To evaluate changes in sinus dimensions immediately postoperatively and 1 year later using a composite of bovine-derived xenograft and autogenous bone for lateral bone augmentation of the maxillary sinus. MATERIALS AND METHODS: Patients who underwent lateral wall sinus augmentation procedures without concomitant implant placement were considered for this retrospective analysis if they had three consecutive panoramic radiographs: pretreatment (T0), immediately after lateral wall sinus augmentation (T1), and approximately 1 year postoperatively (T2). Eighteen subjects aged 47 to 69 years were included. The surgical protocol included grafting with a composite of bovine-derived xenograft and autogenous bone (9:1 ratio). Digital panoramic radiographs were transferred into measurement software, and the following measurements were performed: (1) vertical distance from the alveolar crest to the height of the augmented material, (2) sagittal area of the grafted area, and (3) vertical distance from the alveolar crest to the roof of the maxillary sinus. All measurements were performed by one examiner. Double measurements were performed in nine patients at T2, and the calculated Cronbach's alpha statistic was very high (.9658 to .9882). RESULTS: The mean overall sinus sagittal area was 1,330 +/- 481 mm2 prior to the grafting procedure, when it decreased to 858.2 +/- 436 mm2 (range, 380.7 to 2,134 mm2) immediately postoperatively (P = .0035) and remained stable at 1 year (mean, 882.2 +/- 384 mm2, P > .05). Similarly, the overall area of the grafted material at the time of surgery was 468.3 +/- 208 mm2 and was only slightly reduced at 1 year (422.2 +/- 193 mm2). The midsagittal graft height at T1 (mean, 20.67 +/- 4.5 mm) was insignificantly and minimally reduced at 1 year (mean, 19.35 +/- 4.9 mm). CONCLUSION: The linear dimensions of composite bone-derived xenograft/autogenous bone grafts following lateral wall sinus augmentation exhibited minimal changes during the 8- to 12-month healing period. PMID- 26800166 TI - Comparison of Customized Abutments Made from Titanium and a Machinable Precious Alloy. AB - PURPOSE: To investigate the clinical usefulness, a customized abutment produced with the Pd-Ag-In alloy was compared with a customized abutment produced with the conventional titanium alloy for discoloration and mechanical accuracy. MATERIALS AND METHODS: Discoloration and resistance to corrosion of the Pd-Ag-In alloy were evaluated using chemical solutions. Marginal adaptation of internal-type implants and abutments was compared using 10 titanium abutments and 10 Pd-Ag-In abutments using a surface measuring system. A detorque test was performed on 12 implant abutment complexes of each control and experimental group to investigate screw joint stability. Cyclic loading simulating a human's mastication movement for 1 year was applied after 30 Ncm initial tightening, and the removal torque was measured using a digital torque gauge. The noninferiority test was conducted to compare the Pd-Ag-In alloy with a titanium abutment with a 10% margin. RESULTS: The Pd-Ag-In alloy had a warm yellow color and displayed stable resistance to discoloration and corrosion, resulting in an advantageous esthetic property. When compared to the titanium alloy, it did not show noninferiority with respect to the gap between the implant and the abutment; the gap was approximately 13.3 MUm on average, which was not significantly different from those observed in previous studies. After long-term use, it displayed statistically significant noninferiority in the removal torque value compared to the titanium group. CONCLUSION: The Pd-Ag-In alloy-based customized abutment had good mechanical properties of the implant-abutment complex as well as a superior esthetic property, and can provide favorable outcomes in anterior implant restoration. PMID- 26800168 TI - Crestal Bone Changes Around Implants with Implant-Abutment Connections at Epicrestal Level or Above: Systematic Review and Meta-Analysis. AB - PURPOSE: The aim of this systematic review and meta-analysis was to evaluate crestal bone changes around implants when placing the implant-abutment connection at the crestal bone level or above. MATERIALS AND METHODS: Medline (Pubmed), EMBASE, and Cochrane Library up to January 2014 were electronically and hand searched for any publications that evaluated radiographic crestal bone changes around nonsubmerged, rough-surfaced implants placed in healed sites in humans and loaded for a minimum of 1 year. RESULTS: The search yielded 1,122 publications; 1,106 could not be included. After 16 full-text articles were read and subjected to inclusion and exclusion criteria, four were included. The mean difference was 0.29 mm (95% CI, -0.58 mm to -0.01 mm). Heterogeneity between studies was observed (I2 = 95%). Significantly more crestal bone change was seen in the epicrestal implant-abutment (bone level) connection group when compared to implants with the prosthetic connection above the crestal bone level (tissue level) (P < .00001). CONCLUSION: Dental implants at bone level show significantly less crestal bone change after 1 year of loading than tissue-level implants. PMID- 26800167 TI - Prevalence of Peri-implantitis in Medically Compromised Patients and Smokers: A Systematic Review. AB - PURPOSE: To verify whether the diversity of systemic medical conditions and smoking act as biologic associated factors for peri-implantitis. MATERIALS AND METHODS: The PICO question was: "In patients with osseointegrated dental implants, does the presence of smoking habits or a compromised medical status influence the occurrence of peri-implantitis compared with the presence of good general health?" Smoking and systemic conditions such as type 2 diabetes mellitus, cardiovascular diseases, rheumatoid arthritis, lung diseases, obesity, cancer, deep depression, and osteoporosis were screened. Selection criteria included at least 10 patients per condition, 1 year of follow-up after implant loading, and strict cutoff levels (probing pocket depth [PPD], bleeding on probing [BOP] and/or pus, marginal bone loss) to define peri-implantitis. RESULTS: From the 1,136 records initially retrieved, 57 were selected after title and abstract analyses. However, only six papers were considered for qualitative evaluation. No randomized controlled clinical trial was found. Smoking was associated with peri-implantitis in only one out of four studies. Poorly controlled type 2 diabetes accentuated only PPD and radiographic marginal bone level prevalence rates in peri-implant patients (one study). Cardiovascular disease was considered a risk (one out of two studies). The chance of peri implant patients harboring the Epstein-Barr virus was threefold in one report. No associations were found for rheumatoid arthritis. CONCLUSION: Data from existing studies point to smoking and diabetes as biologic associated factors for peri implantitis. However, the body of evidence is still immature, and the specific contribution of general health problems to peri-implantitis requires additional robust epidemiologic and clinical investigations. PMID- 26800169 TI - Research Waste: How Are Dental Survival Articles Indexed and Reported? AB - PURPOSE: Research waste occurs when research is ignored, cannot be found, cannot be used, or is unintentionally repeated. This article aims to investigate how dental survival analyses were indexed and reported, and to discuss whether errors in indexing and writing articles are affecting identification and use of survival articles, contributing to research waste. MATERIALS AND METHODS: Articles reporting survival of dental prostheses in humans (also known as time-to-event) were identified by searching 50 dental journals that had the highest Impact Factor in 2008. These journals were hand searched twice (Kappa 0.92), and the articles were assessed by two independent reviewers (Kappa 0.86) to identify dental survival articles ("case" articles, n = 95), likely false positives (active controls, n = 91), and all other true negative articles (passive controls, n = 6,769). This means that the study used a case:control method. Once identified, the different groups of articles were assessed and compared. Allocation of medical subject headings (MeSH) by MEDLINE indexers that related to survival was sought, use of words by authors in the abstract and title that related to survival was identified, and use of words and figures by authors that related to survival in the articles themselves was also sought. Differences were assessed with chi-square and Fisher's Exact statistics. Reporting quality was also assessed. The results were reviewed to discuss their potential impact on research waste. RESULTS: Allocation of survival-related MeSH index terms across the three article groups was inconsistent and inaccurate. Statistical MeSH had not been allocated to 30% of the dental survival "case" articles and had been incorrectly allocated to 15% of active controls. Additionally, information reported by authors in titles and abstracts varied, with only two-thirds of survival "case" articles mentioning survival "statistics" in the abstract. In the articles themselves, time-to-event statistical methods, survival curves, and life tables were poorly reported or constructed. Overall, the low quality of indexing by indexers and reporting by authors means that these articles will not be readily identifiable through electronic searches, and, even if they are found, the poor reporting quality makes it unnecessarily difficult for readers to understand and use them. CONCLUSION: There are substantial problems with the reporting of time-to-event analyses in the dental literature. These problems will adversely impact how these articles can be found and used, thereby contributing to research waste. Changes are needed in the way that authors report these studies and the way indexers classify them. PMID- 26800170 TI - Peri-implant Hard and Soft Tissue Stability in Implants Placed Simultaneously Versus Delayed with Intraoral Block Bone Grafts in Horizontal Defects: A Retrospective Case Series Study. AB - PURPOSE: To compare the 3-year outcome of dental implants placed simultaneously or delayed with intraoral onlay block bone grafts. MATERIALS AND METHODS: A retrospective study was conducted of patients subjected to localized lateral alveolar ridge augmentation with intraoral onlay autogenous block bone grafts before or at implant placement between 2005 and 2010 in the Oral Surgery Unit of the University of Valencia (Valencia, Spain). The parameters evaluated at follow up visits were implant survival and success rates, peri-implant soft tissue conditions (Plaque Index and Bleeding Index, probing depth, width of keratinized mucosa, and facial mucosal retraction), radiographic peri-implant marginal bone loss, and patient satisfaction. RESULTS: Thirty-four patients with 53 implants (23 delayed and 30 simultaneous) were included. After 3 years of loading, the cumulative implant success rate was 83.3% for simultaneous and 96.9% for delayed implants (P = .217). Average marginal bone loss was 1.15 +/- 1.67 mm for simultaneously inserted implants and 0.29 +/- 0.35 mm for delayed implants (P < .01). There were no significant differences in Plaque Index or modified Bleeding Index between the groups. Peri-implant facial mucosal recession was more frequent in the simultaneous implant group (26.6% vs. 13%), though the difference was not statistically significant. General patient satisfaction averaged 9.05 +/- 0.82, and good quality of life was reported by all patients. CONCLUSION: Despite its sample size and design limitations, the delayed procedure showed less marginal bone loss and a lower prevalence of facial mucosal recession than the simultaneous implant placement procedure at 3 years postloading. PMID- 26800171 TI - Immediate Loading of Conical Connection Implants: Up-to-2-Year Retrospective Clinical and Radiologic Study. AB - PURPOSE: To report the up-to-2-year outcomes of the immediately loaded novel variable-thread tapered implant with an internal conical connection and built-in platform shifting. MATERIALS AND METHODS: Sixty-four partially and completely edentulous patients were referred to two private centers for implant treatments between December 2010 and June 2012. Clinical and radiographic parameters were assessed retrospectively; the outcomes were implant and prosthetic failure, marginal bone remodeling, and complications. RESULTS: One hundred forty-eight NobelReplace Conical Connection implants were placed in both postextraction sockets (n = 67) and healed sites (n = 81). One maxillary postextractive implant failed before the definitive prosthesis delivery, accounting for a cumulative success rate of 99.3%. No definitive prostheses failed. A mean marginal bone loss (MBL) of 0.42 +/- 1.16 mm and 0.71 +/- 1.53 mm was observed between implant placement and the 1-year (n = 147) and 2-year (n = 74) follow-up periods, respectively. In the postextraction sites, the mean MBL was 0.28 +/- 0.39 mm and 0.69 +/- 0.75 mm at the 1-year (n = 66) and 2-year (n = 50) follow-up periods; in the healed sites, the mean MBL was 0.51 +/- 0.88 mm (n = 81) and 0.62 +/- 0.80 mm (n = 24), respectively. At the 2-year follow-up session (n = 74), bleeding on probing was 8.3%, and the plaque score was 15.7%. No technical complications were observed. One biologic complication (0.8%) was reported. CONCLUSION: Within the limitations of this study and the relatively short follow-up, the immediately loaded NobelReplace Conical Connection implants demonstrated good treatment outcomes with regard to implant and prosthetic survival rate, MBL, and soft tissue conditions, in both postextraction and healed sites. PMID- 26800172 TI - Complete Edentulous Rehabilitation Using an Immediate Function Protocol and an Implant Design Featuring a Straight Body, Anodically Oxidized Surface, and Narrow Tip with Engaging Threads Extending to the Apex of the Implant: A 5-year Retrospective Clinical Study. AB - PURPOSE: To report the 5-year outcome of NobelSpeedy design implants in immediate function fixed prosthetic rehabilitations. MATERIALS AND METHODS: This retrospective clinical study included 46 consecutive patients (29 women and 17 men) with an average age of 55 years (range, 32 to 78 years) who were rehabilitated between 2003 and 2004 with full-arch restorations supported by dental implants in immediate function. The primary outcome measures were implant survival calculated based on implant function and using life tables. The secondary outcome measures were marginal bone levels measured at 3 and 5 years, and the incidence of mechanical and biologic complications. RESULTS: Five patients with 21 study implants dropped out (11%). One-hundred eighty-nine implants were inserted in the maxilla (n = 166) and mandible (n = 23). Five patients lost five implants, giving a cumulative survival rate of 97.3% at 5 years of follow-up. The average (SD) marginal bone levels were 1.45 mm (0.83 mm) and 1.72 mm (1.04 mm) at 5 years of follow-up. The incidence of mechanical complications in the provisional and definitive prostheses was registered in 14 and 6 patients, respectively: prosthetic screw loosening (n = 4 provisional prostheses, n = 3 definitive prostheses), abutment screw loosening (n = 5 provisional prostheses), fracture of the acrylic resin prostheses (n = 5 provisional prostheses, n = 1 definitive prosthesis), chipping of a ceramic crown (n = 1 definitive prosthesis), and fracture of a ceramic crown (n = 1 definitive prosthesis). The incidence of biologic complications (peri-implant pathology) was registered in 6 patients and 12 implants (7.1%). CONCLUSION: Within the limitations of this study, it is possible to conclude that implants of the NobelSpeedy type used in immediate function for support of fixed prosthetic full arch rehabilitations are a valid option, with a high survival rate. PMID- 26800173 TI - Influence of Platform-Switched, Laser-Microtextured Implant on Marginal Bone Level: A 24-Month Case Series Study. AB - PURPOSE: The aim of this case series study was to evaluate clinical and radiographic changes of soft and hard tissues around tapered, platform-switched, laser-microtextured implants 24 months after crown placement. MATERIALS AND METHODS: Twenty tapered, platform-switched, laser-microtextured collar implants were placed in 20 patients. Full-mouth plaque score, full-mouth bleeding score, probing depth, and mucosal recession were recorded at the time of crown cementation and after 24 months follow-up. The marginal bone-level changes at the mesial and distal aspects of the implants were calculated by subtracting from baseline and 24-month implant marginal bone level. RESULTS: In terms of the full mouth plaque score and full-mouth bleeding score, tapered, platform-switched, laser-microtextured implants showed statistically significant improvements at 6 months when compared to baseline (P < .001). Statistically significantly deeper probing depths (P < .001) were found when comparing baseline and at 24 months at mesial, lingual, and distal sites. However, no statistically significant difference was found at the buccal aspects (P = .064). Radiographic marginal bone loss at 2-year follow-up for tapered, platform-switched, laser-microtextured implants was 0.72 +/- 0.16 mm and 0.67 +/- 0.15 mm at the mesial and distal sites, respectively. CONCLUSION: Within the limits of this study, tapered, platform-switched, laser-microtextured implants maintained marginal bone level (less than 1 mm radiographic bone loss) as well as limited mucosa recession over a 2-year period. PMID- 26800174 TI - Six-Year Radiographic, Clinical, and Soft Tissue Outcomes of Immediately Loaded, Straight-Walled, Platform-Switched, Titanium-Alloy Implants with Nanosurface Topography. AB - PURPOSE: This prospective, longitudinal study evaluated the survival, marginal bone levels, and soft tissue conditions for immediately loaded, straight-walled, platform-switched, titanium-alloy implants with an internal connection and nanosurface topography. MATERIALS AND METHODS: Patients were enrolled at a single center. The immediate loading protocol required a final insertion torque >= 25 Ncm, an implant stability quotient (ISQ) > 55, and placement of the provisional prosthesis on the same day as implant placement. Posttreatment follow-up examinations were scheduled at 3, 6, and 12 months and annually thereafter. Soft tissue evaluation consisted of assessment of the implant sites for signs of peri implant infection including mucosal inflammation, bleeding on probing or suppuration, and progressive bone loss. Oral hygiene was evaluated, and radiographic marginal bone levels were analyzed and compared to baseline at the time of provisional loading. RESULTS: Forty-eight consecutively treated patients received 122 implants; 112 qualified for immediate loading and were included. ISQ scores ranged from 51 to 87, with a mean value of 75.1 (SD = 6.8). One implant failed (after 3 months). After an average follow-up period of 6.2 years (SD = 0.37; range, 5.4 to 6.9), no further losses occurred, leading to an overall cumulative survival rate of 99.1%. Average bone loss for the 111 implants after 6 years was 0.35 mm (SD = 0.45; range: -0.35 to 2.20). Four implants (3.6%) in two patients showed concomitant peri-implant infections associated with bleeding on probing and/or purulence after 2 years in function. Exploratory surgery revealed residual submucosal cement. After its removal, the progressive bone loss stopped, and peri-implant tissue in both patients returned to a healthy condition. CONCLUSION: This study based on 40 patients treated with 112 straight-walled, platform-switched, titanium-alloy implants with nanosurface topography yielded a 99.1% survival rate after a mean follow-up time of 6.2 years. Additionally, mean crestal bone loss was limited to 0.26 mm (SD = 0.38) after 1 year and 0.35 mm (SD = 0.45) after 6 years. Peri-implant infection associated with excessive bone loss above 2 mm was only encountered in one implant, and residual cement was shown to be responsible. PMID- 26800176 TI - Reactive Soft Tissue Preservation in Large Bone Defects After Tooth Extractions: A Cone Beam Study. AB - PURPOSE: Reduction of alveolar height and width after tooth extraction may present problems for implant placement, since bone volume is important for biologic and esthetic reasons. The aim of this study was to assess bone healing of large bone defects grafted with collagen sheets and maintenance of reactive soft tissue, evaluating cone beam computed tomography (CBCT) scans and histomorphometric results. MATERIALS AND METHODS: Patients presented large bone defects after tooth extractions. Reactive soft tissue was left in the defects filled by collagen sheets. Vertical bone volume was assessed by CBCT examinations before tooth extractions and 3 months later. At 3 months, cylinder bone samples were obtained for histology and histomorphometry analysis. RESULTS: Twenty-six patients were included in the clinical study. Examined defects reported mean bone gain of 12.13 +/- 3.91 mm, and mean vertical bone levels showed a statistically significant increase (P < .05) at 3 months after extraction. Histologic examinations revealed bone formation; mean vital bone measurements were 41.59% +/ 5.80%, and connective tissue percentages averaged 50.37% +/- 7.73%. CONCLUSION: Reactive soft tissue left in large bone defects after tooth extraction and grafted collagen may support a significant vertical bone gain and vital bone formation. PMID- 26800175 TI - Planning Implant Placement on 3D Stereolithographic Models Applied with Immediate Loading of Implant-Supported Hybrid Prostheses After Multiple Extractions: A Case Series. AB - PURPOSE: The aim of this noninterventional, retrospective case series was to evaluate the outcome of immediately loaded implants in patients with failing dentitions that require bone tabling using a bone reduction guide and a surgical guide manufactured directly on three-dimensional (3D) stereolithographic models. MATERIALS AND METHODS: Consecutive patients with failing dentition and at least two remaining teeth who were treated in a single center between December 14, 2009 and September 23, 2013 were eligible. All patients receiving implants loaded with a hybrid prosthesis on the same day as extraction with their surgery planned on 3D models and performed using a surgical guide manufactured in a laboratory on the planning model were included. Patients who had undergone bone grafting procedures were excluded. Descriptive statistical analyses of available data were performed, including life-table calculations to derive a cumulative survival rate (CSR). RESULTS: Two hundred twenty-eight patients (105 females and 123 males) received 1,657 implants (NobelActive) in 321 arches, in most cases 5 implants (range, 5 to 7) per arch. Ten preexisting implants were used. The mean insertion torque was 60.02 +/- 13.1 Ncm (range, 15 to 75 Ncm). The definitive abutment was placed on the same day as surgery in all cases, and the definitive prosthesis (n = 304) was delivered after a mean of 7.9 +/- 2.6 months. All implants were followed for 20.01 +/- 11.3 months (range, 0 to 52 months) from implant insertion. Four implants (3 patients) had delayed loading, and one implant was left as a sleeping implant. Eight implants among six patients failed, two of the implants after prosthesis delivery. The CSR of the placed implants was 99.4% at implant level and 96.2% at patient level. CONCLUSION: Planning on 3D models to remove bone and place implants using custom-made bone reduction and surgical guides with immediate loading on the same day as extraction of remaining teeth was safe and effective for implant survival and rehabilitation of patients with periodontitis and failing dentition. PMID- 26800177 TI - Comparison of the Primary and Secondary Stability of Implants with Anodized Surfaces and Implants Treated by Acids: A Split-Mouth Randomized Controlled Clinical Trial. AB - PURPOSE: The objective of this randomized controlled clinical split-mouth trial was to compare anodized implant surfaces and implant surfaces modified by acid etching in terms of primary and secondary stability. MATERIALS AND METHODS: Forty six implants were placed bilaterally in the posterior mandibles of 23 patients. Each patient received one implant with a surface treated by acid (AC) and the other with an anodized implant surface (ANO). The selection of the side where the implant was placed was chosen randomly by lot. The implants were evaluated with respect to insertion torque within the surgical bed and primary and secondary stability by testing the implant stability quotient (ISQ) at five different times (immediate postoperative period and 21, 30, 60, and 180 days after surgery). The paired t test was used to compare the two groups, and ANOVA Repeated Measures complemented by the Tukey posttest were used for longitudinal analysis of the implants in each group. All tests were applied with a confidence level of 95% (P < .05). RESULTS: No statistically significant difference was detected between the AC and ANO groups regarding insertion torque. ISQ analysis revealed that the AC group showed statistically higher values than the ANO group at the 21-day period (P < .05); however, no other statistically significant differences were detected at the other times. CONCLUSION: The different surfaces were similar in terms of primary and secondary stability of implants placed in the posterior mandible. PMID- 26800178 TI - Immediate Implant Placement After Removal of Maxillary Impacted Canine Teeth: A Technical Note. AB - Impacted maxillary canine teeth commonly occur in the general population. The traditional therapeutic approach comprises fenestration and orthodontic traction; however, if traction is not feasible or the patient refuses orthodontic treatment, an alternative solution is to remove the impacted tooth and immediately place an implant. This technical note describes a novel surgical approach to rehabilitation after impacted canine tooth removal, entailing immediate placement of a long implant in combination with regenerative materials and a barrier. Of note, this procedure preserves the apical ridge bone crest, allowing implant anchorage and primary stability to be achieved. PMID- 26800179 TI - Assessment of Bone Regeneration Using Adipose-Derived Stem Cells in Critical-Size Alveolar Ridge Defects: An Experimental Study in a Dog Model. AB - PURPOSE: To assess bone regeneration potential of a fibronectin- and adipose derived stem cell-covered ceramic biomaterial in three-wall critical-size alveolar ridge defects. MATERIALS AND METHODS: In 18 dogs, four dehiscence-type and critical-size defects were created surgically in the edentulous alveolar ridge. Defects were randomly regenerated using biomaterials coated with particulate beta-tricalcium phosphate (beta-TCP), beta-TCP with fibronectin (Fn) (beta-TCP-Fn), and beta-TCP with a combination of Fn and autologous adipose derived stem cells (ADSCs) (beta-TCP-Fn-ADSCs), leaving one defect as control. The animals were divided into three groups according to the time of euthanasia (1, 2, or 3 months of healing). RESULTS: At the time of sacrifice, statistically significant differences between the four types of defects in the total area of bone regeneration, percentage of neoformed bone matrix, medullary space, or contact between particulate biomaterial and neoformed bone matrix were not found. All defects showed a significant increase in neoformed bone matrix as sacrifice was delayed, but a uniform pattern was not followed. Only defects treated with beta-TCP-Fn-ADSCs showed a significant increase in the bone regeneration area when animals sacrificed at 3 months were compared to those sacrificed at 1 month (P = .006). CONCLUSION: The use of ADSCs in bone regeneration processes of critical-size defects of the alveolar ridge did not entail an advantage regarding greater bone regeneration as compared with other biomaterials. However, the use of beta-TCP coated with a combination of Fn and ADSCs appeared to favor stabilization of the regenerated area, allowing a more efficient maintenance of the space at 3 months of healing. PMID- 26800180 TI - Multiple Inoculations of Bone Marrow Stromal Cells into Beta-Tricalcium Phosphate/Chitosan Scaffolds Enhances the Formation and Reconstruction of New Bone. AB - PURPOSE: To compare the effects of different cell inoculation strategies on cellular attachment and viability as well as on osteogenic differentiation capacity and subsequent bone graft functionality after implantation of cellularized scaffolds in a mandibular defect rabbit model. MATERIALS AND METHODS: Bone marrow stromal cells (BMSCs) were inoculated into the scaffolds of beta-tricalcium phosphate/chitosan (beta-TCP/CS) either once or multiple times and their efficiency assessed based on cell viability, initial seeding efficiency, alkaline phosphatase activity in cell lysates, mineralization activity in cryosections of cell-seeded scaffolds by von Kossa staining, and osteogenic differentiation on reverse transcriptase polymerase chain reaction. RESULTS: Compared with one-time inoculation of BMSCs, multiple inoculations led to higher cell viability, increased proliferation, more homogeneous distribution in the scaffold, better in vitro osteogenic differentiation, and improved in vivo bone repair in a rabbit model of mandibular defect. CONCLUSION: Multiple inoculations have many advantages over the one-time inoculation method and should be further researched for bone tissue engineering. PMID- 26800181 TI - Double Centrifugation Versus Single Centrifugation of Bone Marrow Aspirate Concentrate in Sinus Floor Elevation: A Pilot Study. AB - PURPOSE: To evaluate the regenerative results of the addition of bone marrow aspirate concentrate, using a single or double centrifugation protocol, to a xenogeneic bone graft in sinus floor elevation. MATERIALS AND METHODS: Using a randomized, controlled pilot study design in 15 consecutive patients, sinus floor elevation procedures were performed with a xenogenous bone graft alone (control group, CG) or associated with bone marrow aspirate concentrate obtained by single centrifugation (single centrifugation group, SCG) or double centrifugation (double centrifugation group, DCG). In the patients in the single and double centrifugation groups, bone marrow was harvested from the iliac bone. Six months after the grafting procedures, bone biopsy specimens were obtained during implant placement and were analyzed by histomorphometry. RESULTS: Histomorphometric analysis revealed a great amount of vital mineralized tissue in SCG followed by DCG when compared with the CG (38.44 +/- 12.34%, 34.63 +/- 9.84%, and 27.30 +/- 5.55%, respectively). SCG and DCG presented smaller amounts of nonvital mineralized tissue when compared with the CG (13.70 +/- 7.50%, 19.63 +/- 8.35%, and 22.79 +/- 9.60%, respectively), thus presenting higher levels of resorption. Although these differences were not statistically significant (P > .05), a tendency toward bone gain in the experimental groups (SCG and DCG) was found. All groups (SCG, DCG, and CG) showed similar levels of nonmineralized tissue (47.87 +/- 6.31%, 45.73 +/- 7.33%, and 49.90 +/- 7.64%, respectively). CONCLUSION: This pilot study indicates that the clinical use of bone marrow aspirate concentrate, obtained by either a single or double centrifugation process, combined with a xenograft for maxillary sinus elevation seems to result in more adequate bone repair. However, clinical trials with a larger number of patients are required. PMID- 26800182 TI - Physical Profile and Impact of a Calcium-Incorporated Implant Surface on Preosteoblastic Cell Morphologic and Differentiation Parameters: A Comparative Analysis. AB - PURPOSE: To assess and compare topographic features and preosteoblastic cell responses of a new hydrothermally treated, calcium-incorporated surface against other commercially available implant surfaces. MATERIALS AND METHODS: Four different surfaces were the subject of comparison in this study: machined (MC), resorbable blast media (RBM), sandblasted/large-grit/acid-etched (SLA), and calcium-incorporated SLA (Ca-SLA). Surface morphology and roughness were first characterized by scanning electron microscope (SEM) and white light interferometer, respectively. Preosteoblastic MC3T3-E1 cells were then cultured on the titanium surfaces. Cell morphology was observed at 24 hours, 48 hours, 7 days, and 15 days by SEM; differentiation was assessed at 7, 11, and 15 days by assaying alkaline phosphatase (ALP) activity and osteocalcin (OCN) levels. RESULTS: Surface characterization revealed nanotopographic features on Ca-SLA. At topographic analysis, SLA and Ca-SLA showed similar roughness values. Significant differences in cell differentiation parameters were found only at 15 days between the SLA surfaces (both Ca-incorporated and nonincorporated) and MC. CONCLUSION: Collectively, this study demonstrated that hydrothermal treatment determines the formation of nanotopography without altering the SLA microtopography. Moreover, Ca-SLA and SLA induce MC3T3-E1 cell differentiation at comparable levels. PMID- 26800183 TI - Effect of Cell Seeding Conditions on the Efficiency of In Vivo Bone Formation. AB - PURPOSE: To optimize methods for seeding cells on granular-type beta-tricalcium phosphate (beta-TCP). MATERIALS AND METHODS: Bone marrow stromal cells were obtained from rat long bones and cultured in flasks with Minimum Essential Medium, Alpha Modification (alphaMEM) supplemented with 10% fetal bovine serum (FBS), dexamethasone, ascorbic acid, beta -glycerophosphate, and antibiotics. The influence of differential cell seeding densities and dynamic cell seeding conditions (rotation) was investigated using different sizes of beta -TCP granules and a subcutaneous implantation model. RESULTS: Higher cell seeding densities contributed to efficient in vivo bone formation. The rotational seeding did not affect the efficiency but contributed to the uniformity. Although the granule size did not affect the efficiency under the conditions used in this study, large granules showed more uniform distribution of bone regeneration, while small granules showed nonuniform but dense bone formation. Mixtures of relatively large and small granules may be beneficial for both uniform and efficient bone regeneration. CONCLUSION: These findings may contribute to stable bone tissue engineering with bone marrow stromal cells and beta -TCP granules as a scaffold. PMID- 26800184 TI - Cannabis: The Issue is Control. AB - Where is the national issue of cannabis (marijuana) regulation going? Recent actions at the State level are moving to guide us to a national perspective on how to control this new marketplace. PMID- 26800185 TI - Life History and Production of the Western Gray Whale's Prey, Ampelisca eschrichtii Kroyer, 1842 (Amphipoda, Ampeliscidae). AB - Ampelisca eschrichtii are among the most important prey of the Western North Pacific gray whales, Eschrichtius robustus. The largest and densest known populations of this amphipod occur in the gray whale's Offshore feeding area on the Northeastern Sakhalin Island Shelf. The remote location, ice cover and stormy weather at the Offshore area have prevented winter sampling. The incomplete annual sampling has confounded efforts to resolve life history and production of A. eschrichtii. Expanded comparisons of population size structure and individual reproductive development between late spring and early fall over six sampling years between 2002 and 2013 however, reveal that A. eschrichtii are gonochoristic, iteroparous, mature at body lengths greater than 15 mm and have a two-year life span. The low frequencies of brooding females, the lack of early stage juveniles, the lack of individual or population growth or biomass increases over late spring and summer, all indicate that growth and reproduction occur primarily in winter, when sampling does not occur. Distinct juvenile and adult size cohorts additionally indicate growth and juvenile production occurs in winter through spring under ice cover. Winter growth thus requires that winter detritus or primary production are critical food sources for these ampeliscid populations and yet, the Offshore area and the Eastern Sakhalin Shelf ampeliscid communities may be the most abundant and productive amphipod population in the world. These A. eschrichtii populations are unlikely to be limited by western gray whale predation. Whether benthic community structure can limit access and foraging success of western gray whales is unclear. PMID- 26800187 TI - Recent pharmacological developments in the treatment of perennial and persistent allergic rhinitis. AB - INTRODUCTION: Allergic rhinitis (AR) has a major negative impact on patients' quality of life (QoL) and carries a high socio economic burden. This is particularly the case for patients who experience symptoms for extended periods of time (i.e. those with perennial (PAR) or persistent AR (PER), depending on the classification system used). This review covers available pharmacological advances and recent developments in the treatment of PAR or PER. AREAS COVERED: Pharmacological AR treatment is used to reduce symptom burden and help restore patients' normal daily routine. Traditionally, non-sedating antihistamines and intranasal corticosteroids (INS) were the two drug classes recommended for use first line. These, along with antileukotrienes, decongestants, mast cell stabilizers and anticholinergics, constituted the bulk of the AR treatment arsenal. MP-AzeFlu (Dymista(r), Meda, Solna, Sweden) is the most recent addition to that arsenal. It is a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) delivered in a single spray and has surpassed available therapies in terms of symptom control and treatment response. Other relatively new treatments for PAR or PER include H3 antihistamines, toll like receptor (TLR) agonists, cellulose powders and micro-emulsions, novel biomolecular formulations and omalizumab. Each of these new additions is reviewed here. EXPERT OPINION: A new AR drug class has recently been introduced (i.e. RO1AD58). Currently MP-AzeFlu is the only treatment option within this drug class. It can be estimated that combination treatments like MP-AzeFlu will become the mainstay of PAR and PER therapy since use will result in better compliance, improved efficacy over INS and a faster response together with good levels of tolerability. The challenge is to find other equally, or more effective, combination treatments, as has been the therapeutic standard in bronchial asthma for decades. The potential of biologics, as well as TLR-agonists and other new treatment options needs to be further evaluated. PMID- 26800186 TI - Vitamin D deficiency at admission is not associated with 90-day mortality in patients with severe sepsis or septic shock: Observational FINNAKI cohort study. AB - Introduction Low levels of vitamin D have been associated with increased mortality in patients that are critically ill. This study explored whether vitamin D levels were associated with 90-day mortality in severe sepsis or septic shock. Methods Plasma vitamin D levels were measured on admission to the intensive care unit (ICU) in a prospective multicentre observational study. Results 610 patients with severe sepsis were included; of these, 178 (29%) had septic shock. Vitamin D deficiency (<50 nmol/L) was present in 333 (55%) patients. The 90-day mortality did not differ among patients with or without vitamin D deficiency (28.3% vs. 28.5%, p = 0.789). Diabetes was more common among patients deficient compared to those not deficient in vitamin D (30% vs. 18%, p < 0.001). Hospital-acquired infections at admission were more prevalent in patients with a vitamin D deficiency (31% vs. 16%, p < 0.001). A multivariable adjusted Cox regression model showed that low vitamin D levels could not predict 90-day mortality (<50 nmol/L: hazard ratio (HR) 0.99 (95% CI: 0.72-1.36), p > 0.9; and <25 nmol/L: HR 0.44 (95% CI: 0.22-0.87), p = 0.018). Conclusions Vitamin D deficiency detected upon ICU admission was not associated with 90-day mortality in patients with severe sepsis or septic shock. Key messages In severe sepsis and septic shock, a vitamin D deficiency upon ICU admission was not associated with increased mortality. Compared to patients with sufficient vitamin D, patients with deficient vitamin D more frequently exhibited diabetes, elevated C-reactive protein levels, and hospital-acquired infections upon ICU admission, and they more frequently developed acute kidney injury. PMID- 26800189 TI - Metabolites in Blood for Prediction of Bacteremic Sepsis in the Emergency Room. AB - A metabolomics approach for prediction of bacteremic sepsis in patients in the emergency room (ER) was investigated. In a prospective study, whole blood samples from 65 patients with bacteremic sepsis and 49 ER controls were compared. The blood samples were analyzed using gas chromatography coupled to time-of-flight mass spectrometry. Multivariate and logistic regression modeling using metabolites identified by chromatography or using conventional laboratory parameters and clinical scores of infection were employed. A predictive model of bacteremic sepsis with 107 metabolites was developed and validated. The number of metabolites was reduced stepwise until identifying a set of 6 predictive metabolites. A 6-metabolite predictive logistic regression model showed a sensitivity of 0.91(95% CI 0.69-0.99) and a specificity 0.84 (95% CI 0.58-0.94) with an AUC of 0.93 (95% CI 0.89-1.01). Myristic acid was the single most predictive metabolite, with a sensitivity of 1.00 (95% CI 0.85-1.00) and specificity of 0.95 (95% CI 0.74-0.99), and performed better than various combinations of conventional laboratory and clinical parameters. We found that a metabolomics approach for analysis of acute blood samples was useful for identification of patients with bacteremic sepsis. Metabolomics should be further evaluated as a new tool for infection diagnostics. PMID- 26800190 TI - Endoscopic ultrasound-guided esophagoenterostomy for a completely obstructed surgical anastomosis. PMID- 26800191 TI - Temporary dumping syndrome after gastric peroral endoscopic myotomy: should we control the glycemia? PMID- 26800192 TI - An easier option for endoscopic ultrasound-guided biliary drainage: cannulation using two antiparallel guidewires. PMID- 26800193 TI - Endoscopic resection of a giant ileal inflammatory fibroid polyp by retrograde double-balloon enteroscopy. PMID- 26800194 TI - Modified percutaneous assisted transprosthetic endoscopic therapy for transgastric ERCP in a gastric bypass patient. PMID- 26800195 TI - Endoscopic removal of a nasogastric tube accidentally ligated to the duodenum after open abdominal surgery. PMID- 26800196 TI - Probe-based confocal laser endomicroscopy (pCLE) images of submucosal growth of a duodenal mucous neck cell adenoma. PMID- 26800197 TI - Esophageal fishbone impaction as a result of ingestion of "trapoen" (Surinamese dried fish). PMID- 26800198 TI - Clinical course after endoscopic submucosal dissection in the rectum leaving a circumferential mucosal defect of 26 cm in length. PMID- 26800199 TI - Through-the-scope self-expanding metal stent placement using newly developed short double-balloon endoscope for the effective management of malignant afferent loop obstruction. PMID- 26800200 TI - Transportations of space, time and self: the role of reading groups in managing mental distress in the community. AB - BACKGROUND: The practice of reading and discussing literature in groups is long established, stretching back into classical antiquity. Although benefits of therapeutic reading groups have been highlighted, research into participants' perceptions of these groups has been limited. AIMS: To explore the experiences of those attending therapeutic reading groups, considering the role of both the group, and the literature itself, in participants' ongoing experiences of distress. METHOD: Eleven participants were recruited from two reading groups in the South-East of England. One focus group was run, and eight individuals self selected for individual interviews. The data were analysed together using a thematic analysis drawing on dialogical theories. RESULTS: Participants described the group as an anchor, which enabled them to use fiction to facilitate the discussion of difficult emotional topics, without referring directly to personal experience. Two aspects of this process are explored in detail: the use of narratives as transportation, helping to mitigate the intensity of distress; and using fiction to explore possibilities, alternative selves and lives. CONCLUSIONS: For those who are interested and able, reading groups offer a relatively de-stigmatised route to exploring and mediating experiences of distress. Implications in the present UK funding environment are discussed. PMID- 26800201 TI - Clinical presentation, allergens, and management of wheat allergy. AB - IgE-mediated allergy to wheat proteins can be caused by exposure through ingestion, inhalation, or skin/mucosal contact, and can affect various populations and age groups. Respiratory allergy to wheat proteins is commonly observed in adult patients occupationally exposed to flour, whereas wheat food allergy is more common in children. Wheat allergy is of growing importance for patients with recurrent anaphylaxis, especially when exercise related. The diagnosis of wheat allergy relies on a consistent clinical history, skin prick testing with well-characterized extracts and specific IgE tests. The accuracy of wheat allergy diagnosis may be improved by measuring IgE responses to several wheat components. However, a high degree of heterogeneity has been found in the recognition pattern of allergens among patient groups with different clinical profiles, as well as within each group. Thus, oral provocation with wheat or the implicated cereal is the reference test for the definitive diagnosis of ingested wheat/cereal allergy. PMID- 26800203 TI - Motor facilitation during action observation: The role of M1 and PMv in grasp predictions. AB - Recent theories propose that movement observation is not a "passive mirror" of ongoing actions but might induce anticipatory activity when predictable movements are observed, e.g., because the action goal is known. Here we investigate this mechanism in a series of 3 experiments, by applying transcranial magnetic stimulation (TMS) to primary motor cortex (M1) while subjects observed either whole hand or precision grasping performed by an actor. We show that corticomotor excitability changes in a grip-specific manner but only once the grip can be decoded based on the observed kinematic cues (Exp. 1). By contrast, presenting informative contextual precues evokes anticipatory modulations in M1 already during the reach phase, i.e., well before the grip type could be observed, a finding in line with a predictive coding account (Exp. 2). Finally, we used paired-pulse (PP) TMS to show that ventral premotor cortex (PMv) facilitates grip specific representations in M1 but only while grip formation is observed. These findings suggest that PMv and M1 interact temporarily and mainly when motor aspects of hand-object interactions are extracted from visual information. By contrast, no sustained input from PMv to M1 seems to be required to maintain action representations that are anticipated based on contextual information or once the grip is formed (Exp. 3). PMID- 26800204 TI - Optical Enhancement in Optoelectronic Devices Using Refractive Index Grading Layers. AB - We enhanced the optical transmittance of a multilayer barrier film by inserting a refractive index grading layer (RIGL). The result indicates that the Fresnel reflection, induced by the difference of refractive indices between Si(x)N(y) and SiO2, is reduced by the RIGL. To eliminate the Fresnel reflection while maintaining high transmittance, the optimized design of grading structures with the RIGL was conducted using an optical simulator. With the RIGL, we achieved averaged transmittance in the visible wavelength region by 89.6%. It is found that the optimized grading structure inserting the multilayer barrier film has a higher optical transmittance (89.6%) in the visible region than that of a no grading sample (82.6%). Furthermore, luminance is enhanced by 14.5% (from 10,190 to 11,670 cd m(-2) at 30 mA cm(-2)) when the grading structure is applied to organic light-emitting diodes. Finally, the results offer new opportunities in development of multilayer barrier films, which assist industrialization of very cost-effective flexible organic electronic devices. PMID- 26800205 TI - Highly sensitive amperometric biosensor based on electrochemically-reduced graphene oxide-chitosan/hemoglobin nanocomposite for nitromethane determination. AB - Nitromethane (CH3NO2) is an important organic chemical raw material with a wide variety of applications as well as one of the most common pollutants. Therefore it is pretty important to establish a simple and sensitive detection method for CH3NO2. In our study, a novel amperometric biosensor for nitromethane (CH3NO2) based on immobilization of electrochemically-reduced graphene oxide (rGO), chitosan (CS) and hemoglobin (Hb) on a glassy carbon electrode (GCE) was constructed. Scanning electron microscopy, infrared spectroscopy and electrochemical methods were used to characterize the Hb-CS/rGO-CS composite film. The effects of scan rate and pH of phosphate buffer on the biosensor have been studied in detail and optimized. Due to the graphene and chitosan nanocomposite, the developed biosensor demonstrating direct electrochemistry with faster electron-transfer rate (6.48s(-1)) and excellent catalytic activity towards CH3NO2. Under optimal conditions, the proposed biosensor exhibited fast amperometric response (<5s) to CH3NO2 with a wide linear range of 5 MUM~1.46 mM (R=0.999) and a low detection limit of 1.5 MUM (S/N=3). In addition, the biosensor had high selectivity, reproducibility and stability, providing the possibility for monitoring CH3NO2 in complex real samples. PMID- 26800206 TI - Applying the miniaturization technologies for biosensor design. AB - Microengineering technologies give us some opportunities in developing high-tech sensing systems that operate with low volumes of samples, integrates one or more laboratory functions on a single substrate, and enables automation. These millimetric sized devices can be produced for only a few dollars, which makes them promising candidates for mass-production. Besides electron beam lithography, stencil lithography, nano-imprint lithography or dip pen lithography, basic photolithography is the technique which is extensively used for the design of microengineered sensing systems. This technique has some advantages such as easy to-manufacture, do not require expensive instrumentation, and allow creation of lower micron-sized patterns. In this review, it has been focused on three different type of microengineered sensing devices which are developed using micro/nano-patterning techniques, microfluidic technology, and microelectromechanics system based technology. PMID- 26800207 TI - Mass spectrometry hyphenated techniques for the analysis of volatiles and peptides in soft cheese: Useful tools for the shelf life optimization. AB - In order to assess the product quality and shelf life of an Italian soft cream cheese under different storage conditions, the volatile and peptide profiles evolution were tested. Volatiles were sampled directly from the head space of cheese packaging by solid-phase microextraction and analyzed by GC-MS. Peptide profiles were obtained by nanoLC-MS/MS, following a novel bioinformatics approach based on scoring distribution associated to the protein hits originating from the database search. In particular, a refined identification by focusing on selected time segments corresponding to the most intense peaks was carried out. A total of 40 compounds including acids, aldehydes, ketones, lactones, alcohols, esters, hydrocarbons, terpene, sulfur, and aromatic compounds were detected. Significant differences in their abundance during the storage in different packagings were observed, as well as an evolution of peptides mainly belonging to alphaS1-casein. The results demonstrated the usefulness of the above-mentioned hyphenated techniques for the determination of the soft cheese shelf life under different storage conditions. PMID- 26800209 TI - Correlates of Marijuana Drugged Driving and Openness to Driving While High: Evidence from Colorado and Washington. AB - AIMS: A potential unintended consequence of legalizing recreational marijuana is increased marijuana-related driving impairment. Some states where recreational marijuana is legal have begun implementing interventions to mitigate driving under the influence (DUI) of marijuana, including media campaigns to increase knowledge about DUI laws. However, little is known about the associations between knowledge of DUI laws and marijuana DUI behavior. In this study, we provide new data from a survey of marijuana users in Colorado and Washington to examine associations between marijuana drugged driving and two potential behavioral precursors of marijuana DUI. We also explore other factors that may influence marijuana DUI. METHODS: Data are from an online survey of marijuana users in Colorado and Washington. Respondents who reported any marijuana use in the past 30 days (n = 865) served as the analytic sample. We examined prevalence of two behavioral outcomes: (1) any driving of a motor vehicle while high in the past year and (2) driving a motor vehicle within 1 hour of using marijuana 5 or more times in the past month. Additional outcomes measuring willingness to drive while high were also assessed. Logistic regressions were used to estimate each outcome as a function of two multi-item scales measuring knowledge of the legal consequences of driving high and perceptions that driving while high is not safe. Additional covariates for potential confounders were included in each model. RESULTS: Prevalence of past-year driving while under the influence of marijuana was 43.6% among respondents. The prevalence of driving within 1 hour of using marijuana at least 5 times in the past month was 23.9%. Increased perception that driving high is unsafe was associated with lower odds of past-year marijuana DUI (OR = 0.31, P < 0.01) and lower past-month odds of driving 5 or more times within 1 hour of using marijuana (OR = 0.26, P < 0.01). Increased knowledge of marijuana DUI laws was also associated with lower odds of each of these outcomes (OR = 0.63, P < 0.01, OR = 0.69, P = 0.02, respectively). Post-estimation Wald tests confirmed the negative associations with marijuana DUI were greater in magnitude for safety perceptions than knowledge of DUI laws. Increased perceptions that driving while high is unsafe was associated with significantly lower willingness to drive after using marijuana while increased knowledge of marijuana DUI laws was not associated with these outcomes. CONCLUSIONS: Despite recent interventions targeting public awareness of the legal consequences of marijuana DUI, our results suggest that knowledge of these laws is a weaker predictor of DUI behavior than perceptions that driving high is unsafe. In addition, safety perceptions predict decreased openness to driving high while knowledge of DUI laws was not associated with openness. These findings suggest that interventions for reducing the incidence of marijuana DUI are likely to be more successful by targeting safety perceptions related to marijuana DUI rather than knowledge of DUI laws. We caution that because these data are limited to an online convenience sample, results may not be generalizable beyond our sample. PMID- 26800210 TI - Cotton Wool Spots after Anti-Vascular Endothelial Growth Factor Therapy for Macular Edema Associated with Central Retinal Vein Occlusion. AB - PURPOSE: To report a case series, whereby we encountered a transient increase in retinal cotton wool spots (CWS) following anti-vascular endothelial growth factor (anti-VEGF) therapy for the treatment of macular edema secondary to central retinal vein occlusion (CRVO). METHODS: Eighteen eyes were treated with intravitreal aflibercept (IVA), and 5 were treated with intravitreal ranibizumab (IVR). Fundus photographs obtained 1 month after initial IVA or IVR injections were retrospectively evaluated for the presence of CWS. RESULTS: Twenty-one (91.3%) patients had the following systemic diseases: hypertension, diabetes mellitus without retinopathy, dyslipidemia, or chronic renal failure requiring dialysis. One month after treatment, reduced macular edema was observed in 21 (91.3%) eyes. Initial injections facilitated complete resolution in 14 eyes, and CWS gradually became fainter with additional injections. CONCLUSION: Some eyes with CRVO-related macular edema can show a transient increase in CWS after initial anti-VEGF therapy; however, macular edema, retinal hemorrhage, and visual acuity were improved in almost every case. PMID- 26800211 TI - High Uric Acid (UA) Negatively Affects Serum Tartrate-Resistant Acid Phosphatase 5b (TRACP 5b) Immunoassay. AB - BACKGROUND: Bone metastases often occur in the majority of patients with advanced cancer, such as prostate cancer, lung cancer and breast cancer. Serum tartrate resistant acid phosphatase 5b (TRACP 5b), a novel bone resorption marker, has been used gradually in the clinics as a specific and sensitive marker of bone resorption for the early diagnosis of cancer patients with bone metastasis. Here, we reported that high concentrations of uric acid (UA) lead to decrease of TRACP 5b levels and determined whether TRACP 5b level was associated with UA in interference experiment. METHODS: A total of 77 patients with high concentrations of UA and 77 healthy subjects were tested to evaluate the differences in their TRACP 5b levels. Serial dilutions of UA were respectively spiked with a known concentration of TRACP 5b standard sample, then Serum TRACP 5b was detected by using bone TRAP(r) Assay. A correction equation was set to eliminate UA-derived TRACP 5b false-decrease. The effect of this correction was evaluated in high-UA individuals. RESULTS: The average TRACP level of the high-UA individuals (1.47 +/ 0.62 U/L) was significantly lower than that of the healthy subjects (2.62 +/- 0.63 U/L) (t-test, p < 0.0001). The UA correction equation derived: DeltaTRACP 5b = -1.9751lgDeltaUA + 3.7365 with an R2 = 0.98899. Application of the UA correction equation resulted in a statistically non-significant difference in TRACP 5b values between the healthy subjects and high-UA individuals (p = 0.24). CONCLUSIONS: High UA concentrations can falsely decrease TRACP 5b levels due to a method-related systematic error. To avoid misdiagnoses or inappropriate therapeutic decisions, increased attention should be paid to UA interference, when TRACP 5b is used for early diagnosis of cancer patients with bone metastasis, evaluation of the aggressiveness of osteosarcoma or prediction of survival in prostate cancer and breast cancer with bone metastases. PMID- 26800212 TI - Maternal postpartum depressive symptoms and infant externalizing and internalizing behaviors. AB - Maternal postpartum depression has been shown to be one of the main predictors of externalizing and internalizing behaviors in toddlers and adolescents. Research suggests that presence of such behaviors can be observed as early as infancy. The current study uses longitudinal data from 247 mothers to examine the relationship between postpartum depressive symptoms at 8 weeks and the infant's externalizing and internalizing behaviors at 12 months. In unadjusted linear regression models, there were associations between postpartum depressive symptoms and infant externalizing behaviors (beta=0.082, SE=0.032, p=0.012) and internalizing behaviors (beta=0.111, SE=0.037, p=0.003). After controlling for potential confounding factors, including maternal age, race, education, home ownership, smoking status in the postpartum period, marital status, parenting stress, and happiness from becoming a parent, the associations between postpartum depressive symptoms and infant externalizing (beta=0.051, SE=0.034, p=0.138) and internalizing behaviors (beta=0.077, SE=0.040, p=0.057) were reduced and became non-significant. Furthermore, in these models the total amount of variance explained was 17.2% (p<0.0001) for externalizing behaviors and 10.5% (p<0.01) for internalizing behaviors; the only significant predictor of externalizing behaviors was maternal age (beta=-0.074, SE=0.030, p=0.014), and of internalizing behaviors was white non-Hispanic ethnicity (beta=-1.33, SE=0.378, p=0.0005). A combined effect of the confounding factors seems to explain the finding of no significant independent association between postpartum depressive symptoms and infant externalizing and internalizing behaviors. PMID- 26800213 TI - Cytokine-Like Protein 1(Cytl1): A Potential Molecular Mediator in Embryo Implantation. AB - Cytokine-like protein 1 (Cytl1), originally described as a protein expressed in CD34+ cells, was recently identified as a functional secreted protein involved in chondrogenesis and cartilage development. However, our knowledge of Cytl1 is still limited. Here, we determined the Cytl1 expression pattern regulated by ovarian hormones at both the mRNA and protein levels. We found that the endometrial expression of Cytl1 in mice was low before or on the first day of gestation, significantly increased during embryo implantation, and then decreased at the end of implantation. We investigated the effects of Cytl1 on endometrial cell proliferation, and the effects on the secretion of leukemia inhibitory factor (LIF) and heparin-binding epidermal growth factor (HB-EGF). We also explored the effect of Cytl1 on endometrial adhesion properties in cell-cell adhesion assays. Our findings demonstrated that Cytl1 is an ovarian hormone dependent protein expressed in the endometrium that enhances the proliferation of HEC-1-A and RL95-2 cells, stimulates endometrial secretion of LIF and HB-EGF, and enhances the adhesion of HEC-1-A and RL95-2 cells to JAR spheroids. This study suggests that Cytl1 plays an active role in the regulation of embryo implantation. PMID- 26800214 TI - Regioselective Oxo-Amination of Alkenes and Enol Ethers with N-Bromosuccinimide Dimethyl Sulfoxide Combination: A Facile Synthesis of alpha-Amino-Ketones and Esters. AB - An unprecedented conversion of alkenes and enol ethers to the corresponding alpha imido carbonyl compounds with excellent regioselectivity and yields has been developed. This oxo-amination process employs readily available N bromosuccinimide (NBS) and secondary amines as N-sources and dimethyl sulfoxide (DMSO) as the oxidant and also leads to the production of amino alcohols in a single step on reduction, thus broadening the scope of this operationally simple reaction. For the first time, the formation of reactive Me2S(+)-O-Br species generated by the interaction of NBS with DMSO has been proven. PMID- 26800215 TI - In vitro experimental investigation of the forces and torque acting on the scaphoid during light grasp. AB - The aim of this study was to measure the magnitude and direction of forces and torque within osteotomized scaphoids within cadaveric wrists during grasping movement of the hand. The mechanical contributions of clinically relevant individual wrist-crossing tendon groups were investigated. Wrists of eight forearms were immobilized in the sagittal, transverse, and coronal plane on a fixation device with unhindered axial gliding. The scaphoid was osteotomized and the fragments stabilized using an interlocking nail. The nail served as a sensor for measurement of inter-fragmentary forces orthogonal and torque around the sensor axis. Thus, torque and cantilever forces were measured which originated between the fragments through co-contraction through the activity of wrist crossing tendons. Grasping movement of the hand induced a mean maximum torque of 0.038 +/- 0.051 Nm and a force of 4.01 +/- 1.71 N on the scaphoid. The isolated activation of thumb tendons resulted in a torque of 9.9 E-3 +/- 7.7 E-3 Nm and a force of 1.42 +/- 0.49 N. Despite immobilization of the wrist, grasping movement of the hand caused substantial forces and torque within the osteotomized scaphoid bone in varying directions and severity among different specimens. These factors may contribute to the development of nonunions and malunions in unstable scaphoid fractures through interfragmentary micromotion. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1734-1742, 2016. PMID- 26800218 TI - Next generation sequencing detection of late onset pompe disease. AB - INTRODUCTION: We report a patient in whom the diagnosis of a treatable disease was delayed for 30 years. METHODS: Recent discoveries of next generation sequencing (NGS) have allowed us to reconsider the diagnosis of limb girdle muscular dystrophy (LGMD) cases of unknown etiology. RESULTS: A 36-year-old man appeared to have LGMD with onset in shoulder girdle muscles, but all sarcolemmal and cytoskeletal proteins tested by immunoblotting and immunohistochemistry gave normal results. He developed respiratory insufficiency and became dependent on overnight ventilation at age 44. By NGS technology, 2 mutations in the GAA gene (intervening sequence 1 and a missense mutation in exon 11) allowed us to make a definite diagnosis of glycogenosis type II (Pompe disease) and start enzyme replacement therapy at age 71. CONCLUSIONS: Mild nondystrophic features on muscle biopsy and respiratory muscle involvement should suggest late-onset Pompe disease in patients with an unclassified LGMD phenotype. NGS may help make the diagnosis. Muscle Nerve 53: 981-983, 2016. PMID- 26800219 TI - Polymorphisms of the GR and HSD11B1 genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison's disease. AB - OBJECTIVE: Glucocorticoid substitution is essential in patients with chronic primary adrenocortical insufficiency (Addison's disease) and both over-treatment and inadequate dosage have deleterious effects. Individual sensitivity to glucocorticoids is partly genetically determined. CONTEXT: To test the hypothesis whether the well-characterized SNPs of the GR and HSD11B1 genes may modulate the individual sensitivity to exogenous glucocorticoids and may influence clinical and/or laboratory parameters and the glucocorticoid substitution dosage in patients with Addison's disease. PATIENTS AND METHODS: 68 patients with primary adrenocortical insufficiency were involved. Clinical and laboratory data, as well as the dosage of the hormone replacement therapy were collected. Peripheral blood DNA was isolated, and the GR and HSD11B1 SNPs were examined using allele-specific PCR or Taqman assay on Real Time PCR. RESULTS: The allele frequency of the GR N363S polymorphism was higher in patients compared to the control group and the disease appeared significantly earlier in patients harbouring the GR A3669G compared to noncarriers. These patients had higher ACTH level measured at the time of diagnosis. Homozygous BclI carriers had higher body mass index (BMI) and lower total hydrocortisone equivalent supplementation dose needed than heterozygous or noncarriers. The BMI and weight gain during hormone replacement therapy were also higher in carriers of the HSD11B1 rs4844880 treated with glucocorticoids other than dexamethasone. CONCLUSION: The BclI polymorphism of the GR gene and the rs4844880 of the HSD11B1 gene may contribute to weight gain and may affect the individual need of glucocorticoid substitution dose in these patients. PMID- 26800220 TI - High Out-of-Pocket Medical Spending among the Poor and Elderly in Nine Developed Countries. AB - OBJECTIVE: The design of health insurance, and the role out-of-pocket (OOP) payments play in it, is a key policy issue as rising health costs have encouraged greater cost-sharing measures. This paper compares the percentage of Americans spending large amounts OOP to meet their health needs with percentages in eight other developed countries. By disaggregating by age and income, the paper focuses on the poor and elderly populations within each. DATA SOURCE: The study uses nationally representative household survey data made available through the Luxembourg Income Study. It includes nations with high, medium, and low levels of OOP spending. STUDY DESIGN: Households have high medical spending when their OOP expenditures exceed a threshold share of income. I calculate the share of each nation's population, as well as subpopulations within it, with high OOP expenditures. PRINCIPAL FINDINGS: The United States is not alone in exposing large numbers of citizens to high OOP expenses. In six of the other eight countries, one-quarter or more of low-income citizens devoted at least 5 percent of their income to OOP expenses, and in all but two countries, more than 1 in 10 elderly citizens had high medical expenses. CONCLUSIONS: For some populations in the sample nations, health insurance does not provide adequate financial protection and likely contributes to inequities in health care delivery and outcomes. PMID- 26800221 TI - Continuous Cavitation Designed for Enhancing Radiofrequency Ablation via a Special Radiofrequency Solidoid Vaporization Process. AB - Lowering power output and radiation time during radiofrequency (RF) ablation is still a challenge. Although it is documented that metal-based magnetothermal conversion and microbubbles-based inertial cavitation have been tried to overcome above issues, disputed toxicity and poor magnetothermal conversion efficiency for metal-based nanoparticles and violent but transient cavitation for microbubbles are inappropriate for enhancing RF ablation. In this report, a strategy, i.e., continuous cavitation, has been proposed, and solid menthol-encapsulated poly lactide-glycolide acid (PLGA) nanocapsules have been constructed, as a proof of concept, to validate the role of such a continuous cavitation principle in continuously enhancing RF ablation. The synthesized PLGA-based nanocapsules can respond to RF to generate menthol bubbles via distinctive radiofrequency solidoid vaporization (RSV) process, meanwhile significantly enhance ultrasound imaging for HeLa solid tumor, and further facilitate RF ablation via the continuous cavitation, as systematically demonstrated both in vitro and in vivo. Importantly, this RSV strategy can overcome drawbacks and limitations of acoustic droplet vaporization (ADV) and optical droplet vaporization (ODV), and will probably find broad applications in further cancer theranostics. PMID- 26800222 TI - Photochemical Reduction of Low Concentrations of CO2 in a Porous Coordination Polymer with a Ruthenium(II)-CO Complex. AB - Direct use of low pressures of CO2 as a C1 source without concentration from gas mixtures is of great interest from an energy-saving viewpoint. Porous heterogeneous catalysts containing both adsorption and catalytically active sites are promising candidates for such applications. Here, we report a porous coordination polymer (PCP)-based catalyst, PCP-Ru(II) composite, bearing a Ru(II) -CO complex active for CO2 reduction. The PCP-Ru(II) composite showed improved CO2 adsorption behavior at ambient temperature. In the photochemical reduction of CO2 the PCP-Ru(II) composite produced CO, HCOOH, and H2 . Catalytic activity was comparable with the corresponding homogeneous Ru(II) catalyst and ranks among the highest of known PCP-based catalysts. Furthermore, catalytic activity was maintained even under a 5 % CO2 /Ar gas mixture, revealing a synergistic effect between the adsorption and catalytically active sites within the PCP-Ru(II) composite. PMID- 26800223 TI - A genetic and physical study of the interdomain linker of E. Coli AraC protein--a trans-subunit communication pathway. AB - Genetic experiments with full length AraC and biophysical experiments with its dimerization domain plus linker suggest that arabinose binding to the dimerization domain changes the properties of the inter-domain linker which connects the dimerization domain to the DNA binding domain via interactions that do not depend on the DNA binding domain. Normal AraC function was found to tolerate considerable linker sequence alteration excepting proline substitutions. The proline substitutions partially activate transcription even in the absence of arabinose and hint that a structural shift between helix and coil may be involved. To permit fluorescence anisotropy measurements that could detect arabinose-dependent dynamic differences in the linkers, IAEDANS was conjugated to a cysteine residue substituted at the end of the linker of dimerization domain. Arabinose, but not other sugars, decreased the steady-state anisotropy, indicating either an increase in mobility and/or an increase in the fluorescence lifetime of the IAEDANS. Time-resolved fluorescence measurements showed that the arabinose-induced anisotropy decrease did not result from an increase in the excited-state lifetime. Hence arabinose-induced decreases in anisotropy appear to result from increased tumbling of the fluorophore. Arabinose did not decrease the anisotropy in mutants incapable of binding arabinose nor did it alter the anisotropy when IAEDANS was conjugated elsewhere in the dimerization domain. Experiments with heterodimers of the dimerization domain showed that the binding of arabinose to one subunit of the dimer decreases the fluorescence anisotropy of only a fluorophore on the linker of the other subunit. PMID- 26800225 TI - Relationship between chromatographic resolution and amide structure of chiral 2 hydroxy acids as O-(-)-menthoxycarbonylated diastereomeric derivatives for enantiomeric separation on achiral gas chromatography. AB - The relationship between chromatographic resolution and amide structure of chiral 2-hydroxy acids as O-(-)-menthoxycarbonylated diastereomeric derivatives on achiral gas chromatography was investigated to elucidate the best diastereomeric conformation for enantiomeric separation of chiral 2-hydroxy acids. Thirteen chiral 2-hydroxy acids were converted into nine different diastereomeric O-(-) menthoxycarbonylated amide derivatives using the primary, secondary and cyclic amines to achieve complete enantiomeric separation through an achiral column. Each enantiomeric pair of 2-hydroxy acids as O-(-)-menthoxycarbonylated tert butylamide derivatives was resolved on both the DB-5 and DB-17 columns with resolution factors ranging from 1.7 to 4.8 and 1.7 to 3.4, respectively. The results revealed that the structure of the amide moiety is shown to significantly affect chromatographic resolution. In addition, O-(-)-menthoxycarbonylated tert butylamide derivatives were shown to be the best diastereomeric conformations for enantiomeric separation of 2-hydroxy acids. When comparing with our previous O trifluoroacetylated(-)-menthyl ester derivatization method, the present results suggested that size differences between groups attached to the chiral center and conformational rigidity can have stronger effects on resolution than the distance between chiral centers. The elution of R- and S-stereoisomers was affected by the class of amine; i.e., primary, secondary, or cyclic, regardless of the substituents on the amine group, the structure of the 2-hydroxy acid, and the polarity of the column. PMID- 26800227 TI - Can Carbon Nanomaterials Improve CZTS Photovoltaic Devices? Evaluation of Performance and Impacts Using Integrated Life-Cycle Assessment and Decision Analysis. AB - In emergent photovoltaics, nanoscale materials hold promise for optimizing device characteristics; however, the related impacts remain uncertain, resulting in challenges to decisions on strategic investment in technology innovation. We integrate multi-criteria decision analysis (MCDA) and life-cycle assessment (LCA) results (LCA-MCDA) as a method of incorporating values of a hypothetical federal acquisition manager into the assessment of risks and benefits of emerging photovoltaic materials. Specifically, we compare adoption of copper zinc tin sulfide (CZTS) devices with molybdenum back contacts to alternative devices employing graphite or graphene instead of molybdenum. LCA impact results are interpreted alongside benefits of substitution including cost reductions and performance improvements through application of multi-attribute utility theory. To assess the role of uncertainty we apply Monte Carlo simulation and sensitivity analysis. We find that graphene or graphite back contacts outperform molybdenum under most scenarios and assumptions. The use of decision analysis clarifies potential advantages of adopting graphite as a back contact while emphasizing the importance of mitigating conventional impacts of graphene production processes if graphene is used in emerging CZTS devices. Our research further demonstrates that a combination of LCA and MCDA increases the usability of LCA in assessing product sustainability. In particular, this approach identifies the most influential assumptions and data gaps in the analysis and the areas in which either engineering controls or further data collection may be necessary. PMID- 26800228 TI - The damage caused by Callosobruchus maculatus on cowpea grains is dependent on the plant genotype. AB - BACKGROUND: Beans from cowpea cultivars fertilized with mineral N or inoculated with various rhizobium strains may contain different nitrogen concentrations and nitrogen metabolite composition, which affects the beans' defense mechanisms against pests. In this study, the population growth of Callosobruchus maculatus reared on beans from four cowpea cultivars fertilized with different nitrogen sources was evaluated. The factors tested were beans from four cowpea cultivars and seven different nitrogen sources: mineral N fertilization, inoculation with five strains of symbiotic diazotrophic bacteria, and soil nitrogen (absolute control). RESULTS: BRS Tapaihum and BRS Acaua cultivars had lower cumulative emergence and instantaneous rate of population growth of the insects compared with other cultivars, indicating antixenosis resistance against C. maculatus. Inoculation of BRS Acaua cultivar with the diazotrophic bacteria strain BR 3299 resulted in higher mortality of C. maculatus. For BRS Tapaihum cultivar, inoculation with diazotrophic bacteria strains BR3267, BR 3262 and BR 3299, and nitrogen fertilization resulted in higher mortality among C. maculatus. CONCLUSION: BRS Tapaihum and BRS Acaua cultivars showed the lowest cumulative insect emergence and instantaneous rates of population growth, and the highest insect mortality, mainly when the grains were obtained from plants inoculated with rhizobial strains. (c) 2016 Society of Chemical Industry. PMID- 26800229 TI - Attentional Bias in Patients with Decompensated Tinnitus: Prima Facie Evidence from Event-Related Potentials. AB - Tinnitus refers to the auditory perception of sound in the absence of external sound or electric stimuli. The influence of tinnitus on cognitive processing is at the cutting edge of ongoing tinnitus research. In this study, we adopted an objective indicator of attentional processing, i.e. the mismatch negativity (MMN), to assess the attentional bias in patients with decompensated tinnitus. Three kinds of pure tones, D1 (8,000 Hz), S (8,500 Hz) and D2 (9,000 Hz), were used to induce event-related potentials (ERPs) in the normal ear. Employing the oddball paradigm, the task was divided into two blocks in which D1 and D2 were set as deviation stimuli, respectively. Only D2 induced a significant MMN in the tinnitus group, while neither D1 nor D2 was able to induce MMN in the control group. In addition, the ERPs in the left hemisphere, which were recorded within the time window of 90-150 ms (ERP 90-150 ms), were significantly higher than those in the right hemisphere in the tinnitus group, while no significant difference was observed in the control group. Lastly, the amplitude of ERP 90-150 ms in the tinnitus group was significantly higher than that in the control group. These findings suggest that patients with decompensated tinnitus showed automatic processing of acoustic stimuli, thereby indicating that these patients allocated more cognitive resources to acoustic stimulus processing. We suggest that the difficulty in disengaging or facilitated attention of patients might underlie this phenomenon. The limitations of the current study are discussed. PMID- 26800230 TI - "Hairy" cells in acute promyelocytic leukemia: Excess myeloperoxidase with formation of needle-shaped crystalline projections on the cytochemical stain in a case with variant morphology. PMID- 26800231 TI - A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis. AB - BACKGROUND: Plaque psoriasis is a chronic and often debilitating skin disorder and proinflammatory cytokines are known to play a key role in the disease process. OBJECTIVES: To evaluate the safety and efficacy of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis in a randomized, double-blind, placebo-controlled, dose-ranging phase 2b study. METHODS: Patients were randomized (n = 271) to receive placebo or oral baricitinib at 2, 4, 8 or 10 mg once daily for 12 weeks (Part A). Dose adjustment for 12 additional weeks was based on percentage improvement in the Psoriasis Area and Severity Index (PASI) score. The primary end point was Psoriasis Area and Severity Index (PASI) 75% (PASI-75) at 12 weeks for North American patients (n = 238); secondary end points were safety and efficacy measures in the entire population. RESULTS: At week 12, more North American patients in the 8-mg (43%) and 10-mg (54%) baricitinib groups than in placebo group (17%; P < 0.05) achieved PASI-75. All baricitinib-treated groups had greater mean changes from baseline in their PASI scores (P < 0.05) at 12 weeks and (except 2 mg) had higher rates of PASI-50 than the placebo group; statistically significant PASI-90 responses were achieved in the 8-mg and 10-mg groups at 8 and 12 weeks. More than 81% of PASI-75 responders maintained their scores through 24 weeks. During Part A, study discontinuations due to adverse events (AEs) were 0%, 0%, 2.8%, 6.3% and 5.8% and treatment-emergent AE rates were 44%, 50%, 47%, 58% and 64% for placebo and 2-, 4 , 8- and 10-mg baricitinib groups, respectively. No opportunistic infections were observed in any treatment group. Dose-dependent changes in laboratory values were observed. CONCLUSIONS: Patients with moderate-to-severe psoriasis treated with baricitinib for 12 weeks achieved significant improvements in PASI-75. PMID- 26800232 TI - Treatment efficacy and safety of ultrasound-guided percutaneous bipolar radiofrequency ablation for benign thyroid nodules. AB - OBJECTIVE: To evaluate the therapeutic efficacy and safety of ultrasound-guided percutaneous bipolar radiofrequency ablation (BRFA) of benign thyroid nodules by comparison with a matched untreated control group. METHODS: The therapeutic efficacy and safety in 35 patients who were subjected to a single session of ultrasound-guided percutaneous BRFA (Group A) for benign thyroid nodules were compared with those in 35 untreated patients (Group B) with benign nodules. The benign nature of all the nodules was confirmed by ultrasound-guided fine-needle aspiration biopsy (FNAB), and all the patients had normal thyroid functions. BRFA was performed with a bipolar electrode (CelonProSurge 150-T20) with an output power of 20 W. Nodule volume, thyroid function and clinical symptoms of all the patients were compared before treatment and during follow-up. RESULTS: In Group A, the BRFA procedures were completed with a mean time of 10.02 +/- 3.30 min (range, 5.47-16.03 min) and with a mean total energy deposition of 10.747 +/- 3704 J (range, 5510-17.770 J). The procedures were tolerated well in all the patients without causing any major complications. At the 6-month follow-up, all of the nodule volume decreased significantly (from 8.81 +/- 8.66 to 1.59 +/- 1.55 ml, p < 0.001) in Group A, whereas the nodule volume increased from 6.90 +/- 3.77 to 7.87 +/- 3.95 ml in Group B (p < 0.001). All (100%) the 35 nodules in Group A had volume reduction ratios (VRRs) of >50%, among which 3 (8.57%) had VRRs >90%. In Group A, the clinical symptoms of the patients who had symptoms before BRFA disappeared, whereas in Group B, the patients had no resolution of clinical symptoms at the 6-month follow-up. CONCLUSION: Ultrasound-guided percutaneous BRFA seems to be an effective and safe method for the treatment of benign thyroid nodules. It may gain a wide use in clinical practice. ADVANCES IN KNOWLEDGE: Based on the comparable efficacy and clinical symptoms between the BRFA and untreated groups, the technique of BRFA can be used as an effective and safe method for the treatment of benign thyroid nodules. PMID- 26800233 TI - Comparative genomics reveals new evolutionary and ecological patterns of selenium utilization in bacteria. AB - Selenium (Se) is an important micronutrient for many organisms, which is required for the biosynthesis of selenocysteine, selenouridine and Se-containing cofactor. Several key genes involved in different Se utilization traits have been characterized; however, systematic studies on the evolution and ecological niches of Se utilization are very limited. Here, we analyzed more than 5200 sequenced organisms to examine the occurrence patterns of all Se traits in bacteria. A global species map of all Se utilization pathways has been generated, which demonstrates the most detailed understanding of Se utilization in bacteria so far. In addition, the selenophosphate synthetase gene, which is used to define the overall Se utilization, was also detected in some organisms that do not have any of the known Se traits, implying the presence of a novel Se form in this domain. Phylogenetic analyses of components of different Se utilization traits revealed new horizontal gene transfer events for each of them. Moreover, by characterizing the selenoproteomes of all organisms, we found a new selenoprotein rich phylum and additional selenoprotein-rich species. Finally, the relationship between ecological environments and Se utilization was investigated and further verified by metagenomic analysis of environmental samples, which indicates new macroevolutionary trends of each Se utilization trait in bacteria. Our data provide insights into the general features of Se utilization in bacteria and should be useful for a further understanding of the evolutionary dynamics of Se utilization in nature. PMID- 26800234 TI - Assembly of the Caenorhabditis elegans gut microbiota from diverse soil microbial environments. AB - It is now well accepted that the gut microbiota contributes to our health. However, what determines the microbiota composition is still unclear. Whereas it might be expected that the intestinal niche would be dominant in shaping the microbiota, studies in vertebrates have repeatedly demonstrated dominant effects of external factors such as host diet and environmental microbial diversity. Hypothesizing that genetic variation may interfere with discerning contributions of host factors, we turned to Caenorhabditis elegans as a new model, offering the ability to work with genetically homogenous populations. Deep sequencing of 16S rDNA was used to characterize the (previously unknown) worm gut microbiota as assembled from diverse produce-enriched soil environments under laboratory conditions. Comparisons of worm microbiotas with those in their soil environment revealed that worm microbiotas resembled each other even when assembled from different microbial environments, and enabled defining a shared core gut microbiota. Community analyses indicated that species assortment in the worm gut was non-random and that assembly rules differed from those in their soil habitat, pointing at the importance of competitive interactions between gut-residing taxa. The data presented fills a gap in C. elegans biology. Furthermore, our results demonstrate a dominant contribution of the host niche in shaping the gut microbiota. PMID- 26800235 TI - Niche partitioning and biogeography of high light adapted Prochlorococcus across taxonomic ranks in the North Pacific. AB - The distribution of major clades of Prochlorococcus tracks light, temperature and other environmental variables; yet, the drivers of genomic diversity within these ecotypes and the net effect on biodiversity of the larger community are poorly understood. We examined high light (HL) adapted Prochlorococcus communities across spatial and temporal environmental gradients in the Pacific Ocean to determine the ecological drivers of population structure and diversity across taxonomic ranks. We show that the Prochlorococcus community has the highest diversity at low latitudes, but seasonality driven by temperature, day length and nutrients adds complexity. At finer taxonomic resolution, some 'sub-ecotype' clades have unique, cohesive responses to environmental variables and distinct biogeographies, suggesting that presently defined ecotypes can be further partitioned into ecologically meaningful units. Intriguingly, biogeographies of the HL-I sub-ecotypes are driven by unique combinations of environmental traits, rather than through trait hierarchy, while the HL-II sub-ecotypes appear ecologically similar, thus demonstrating differences among these dominant HL ecotypes. Examining biodiversity across taxonomic ranks reveals high-resolution dynamics of Prochlorococcus evolution and ecology that are masked at phylogenetically coarse resolution. Spatial and seasonal trends of Prochlorococcus communities suggest that the future ocean may be comprised of different populations, with implications for ecosystem structure and function. PMID- 26800236 TI - Deciphering associations between dissolved organic molecules and bacterial communities in a pelagic marine system. AB - Dissolved organic matter (DOM) is the main substrate and energy source for heterotrophic bacterioplankton. To understand the interactions between DOM and the bacterial community (BC), it is important to identify the key factors on both sides in detail, chemically distinct moieties in DOM and the various bacterial taxa. Next-generation sequencing facilitates the classification of millions of reads of environmental DNA and RNA amplicons and ultrahigh-resolution mass spectrometry yields up to 10 000 DOM molecular formulae in a marine water sample. Linking this detailed biological and chemical information is a crucial first step toward a mechanistic understanding of the role of microorganisms in the marine carbon cycle. In this study, we interpreted the complex microbiological and molecular information via a novel combination of multivariate statistics. We were able to reveal distinct relationships between the key factors of organic matter cycling along a latitudinal transect across the North Sea. Total BC and DOM composition were mainly driven by mixing of distinct water masses and presumably retain their respective terrigenous imprint on similar timescales on their way through the North Sea. The active microbial community, however, was rather influenced by local events and correlated with specific DOM molecular formulae indicative of compounds that are easily degradable. These trends were most pronounced on the highest resolved level, that is, operationally defined 'species', reflecting the functional diversity of microorganisms at high taxonomic resolution. PMID- 26800237 TI - Small, abnormal B lymphoid blast populations in chronic myelogenous leukemia at diagnosis: Does this finding indicate an accelerated course? AB - BACKGROUND: The 2008 WHO is not specific regarding subclassification of chronic myelogenous leukemia (CML) with less than 20% abnormal B lymphoid blasts (ABLB), and suggests patients with ABLB often show rapid progression (Swerdlow, 2008). Recent studies have shown variable outcomes when small abnormal B cell populations are seen by flow cytometry (El Rassi et al., Cancer 2015; 121:872 875; Vrotsos et al., Cytometry B Clin Cytom 2015). METHODS: The hematopathology database was searched (7.4-year period), and patients identified through routine clinical study, who were BCR-ABL1 positive CML and had an ABLB of less than 20%. Flow cytometric (FC) and histologic data was evaluated to determine immunophenotypic abnormalities, immunohistochemical patterns, and percentage of ABLB, hematogones, and mature B cells. RESULTS: Seven patients with CML and ABLB identified by FC studies were found, five of which also had available histologic material to review. ABLB by FC ranged from 0.006% to 3.4%, typically demonstrated an immunophenotype with increased CD10, increased CD19, and decreased CD38, without myeloid antigens, abnormalities similar to that reported previously (Vrotsos et al., Cytometry B Clin Cytom 2015). The ABLB population was found only in diagnostic samples and always with more numerous hematogones. By immunohistochemistry, three of five patients showed >=10% TdT positive cells. All patients showed a response to tyrosine kinase inhibitor therapy, and no patients progressed to clinical lymphoid blast phase. CONCLUSIONS: Immature B cells, occasionally including a small subset with an abnormal phenotype can be observed in chronic phase CML at diagnosis. We believe an approach incorporating clinical data, cytogenetic/molecular findings, and morphologic evaluation may be helpful when determining the best management of CML patients at diagnosis if small ABLB populations are identified by FC. (c) 2016 Clinical Cytometry Society. PMID- 26800238 TI - Contribution of insula in Parkinson's disease: A quantitative meta-analysis study. AB - The insula region is known to be an integrating hub interacting with multiple brain networks involved in cognitive, affective, sensory, and autonomic processes. There is growing evidence suggesting that this region may have an important role in Parkinson's disease (PD). Thus, to investigate the functional organization of the insular cortex and its potential role in parkinsonian features, we used a coordinate-based quantitative meta-analysis approach, the activation likelihood estimation. A total of 132 insular foci were selected from 96 published experiments comprising the five functional categories: cognition, affective/behavioral symptoms, bodily awareness/autonomic function, sensorimotor function, and nonspecific resting functional changes associated with the disease. We found a significant convergence of activation maxima related to PD in different insular regions including anterior and posterior regions bilaterally. This study provides evidence of an important functional distribution of different domains within the insular cortex in PD, particularly in relation to nonmotor aspects, with an influence of medication effect. PMID- 26800239 TI - The genetic background affects the vascular response in T-type calcium channels 3.2 deficient mice. PMID- 26800240 TI - Yin Yang 1-mediated epigenetic silencing of tumour-suppressive microRNAs activates nuclear factor-kappaB in hepatocellular carcinoma. AB - Enhancer of zeste homolog 2 (EZH2) catalyses histone H3 lysine 27 trimethylation (H3K27me3) to silence tumour-suppressor genes in hepatocellular carcinoma (HCC) but the process of locus-specific recruitment remains elusive. Here we investigated the transcription factors involved and the molecular consequences in HCC development. The genome-wide distribution of H3K27me3 was determined by chromatin immunoprecipitation coupled with high-throughput sequencing or promoter array analyses in HCC cells from hepatitis B virus (HBV) X protein transgenic mouse and human cell models. Transcription factor binding site analysis was performed to identify EZH2-interacting transcription factors followed by functional characterization. Our cross-species integrative analysis revealed a crucial link between Yin Yang 1 (YY1) and EZH2-mediated H3K27me3 in HCC. Gene expression analysis of human HBV-associated HCC specimens demonstrated concordant overexpression of YY1 and EZH2, which correlated with poor survival of patients in advanced stages. The YY1 binding motif was significantly enriched in both in vivo and in vitro H3K27me3-occupied genes, including genes for 15 tumour suppressive microRNAs. Knockdown of YY1 reduced not only global H3K27me3 levels, but also EZH2 and H3K27me3 promoter occupancy and DNA methylation, leading to the transcriptional up-regulation of microRNA-9 isoforms in HCC cells. Concurrent EZH2 knockdown and 5-aza-2'-deoxycytidine treatment synergistically increased the levels of microRNA-9, which reduced the expression and transcriptional activity of nuclear factor-kappaB (NF-kappaB). Functionally, YY1 promoted HCC tumourigenicity and inhibited apoptosis of HCC cells, at least partially through NF-kappaB activation. In conclusion, YY1 overexpression contributes to EZH2 recruitment for H3K27me3-mediated silencing of tumour-suppressive microRNAs, thereby activating NF-kappaB signalling in hepatocarcinogenesis. PMID- 26800241 TI - Enantioselective Oxidative Rearrangements with Chiral Hypervalent Iodine Reagents. AB - A stereoselective hypervalent iodine-promoted oxidative rearrangement of 1,1 disubstituted alkenes has been developed. This practically simple protocol provides access to enantioenriched alpha-arylated ketones without the use of transition metals from readily accessible alkenes. PMID- 26800242 TI - Sex differences in depressive effects of experiencing spousal bereavement. AB - AIM: Spousal death is a significant event that becomes a turning point in an individual's life. Widowed persons experience new circumstances, which might induce depression. However, the effects of spousal death on depression can differ by sex and culture. Thus, the present study examined the association between depressive levels and experience of spousal death in Korean adults aged older than 45 years. METHODS: The data were from the Korean Longitudinal Study of Aging from 2010 to 2012. The analysis used frequency analysis to compare the distribution of demographic variables between men and women, and anova to compare 10-item short-form Center for Epidemiological Studies Depression Scale scores as the dependent variable among comparison groups. We also carried out linear mixed model analysis on the association between the 10-item short-form Center for Epidemiological Studies Depression Scale and experience of spousal death. RESULTS: Among 5481 respondents, 2735 were men and 2741 were women. The number of men and women who experienced spousal death were 43 (1.6%) and 181 (6.6%), respectively. Men had lower depressive levels than women when they had been married (men 2.99, women 3.64). Both men and women experiencing spousal death had significantly higher 10-item short-form Center for Epidemiological Studies Depression Scale scores than married men and women (men beta = 0.911, P = 0.003; women beta = 0.512, P = 0.001; ref: no experience of spousal death). CONCLUSIONS: There was a significant association between experience of spousal death and depressive level for both men and women. We suggest that policy practitioners promote community programs that provide bereaved adults with easy access to meaningful social participation and support the minimum cost of living of the widowed. Geriatr Gerontol Int 2017; 17: 322-329. PMID- 26800244 TI - Remodeling and Enhancing Schmidt Reaction Pathways in Hexafluoroisopropanol. AB - The effect of carrying out two variations of the Schmidt reaction with ketone electrophiles in hexafluoroisopropanol (HFIP) solvent has been studied. When TMSN3 is reacted with ketones in the presence of triflic acid (TfOH) promoter, tetrazoles are obtained as the major products. This observation is in contrast to established methods, which usually lead to amides or lactams arising from formal NH insertion as the major products. The full product profiles of several examples of this reaction are also reported and found to include mechanistically interesting products (e.g., double ring expansion). Application of TfOH promoter in HFIP was also found to promote the reaction of a hydroxyalkyl azide with a ketone, which affords lactams following nucleophilic opening of initially formed iminium ether more efficiently than previously reported methods. PMID- 26800243 TI - What influences Latino grocery shopping behavior? Perspectives on the small food store environment from managers and employees in San Diego, California. AB - To inform the design of a multilevel in-store intervention, this qualitative study utilized in-depth semistructured interviews with 28 managers and 10 employees of small-to-medium-sized Latino food stores (tiendas) in San Diego, California, to identify factors within the tienda that may influence Latino customers' grocery-shopping experiences and behaviors. Qualitative data analysis, guided by grounded theory, was performed using open coding. Results suggest that future interventions should focus on the physical (i.e., built structures) and social (i.e., economic and sociocultural) dimensions of store environments, including areas where the two dimensions interact, to promote the purchase of healthy food among customers. PMID- 26800245 TI - A comparison of plasma glucose and oxidative status in lactating dairy cows in summer and autumn. AB - The objective of this study was to investigate the effects of the hot summer season on plasma glucose and oxidative stress markers. For two 14-day experimental periods, namely periods 1 (July-August) and 2 (October-November), 12 and 14 lactating dairy cows, respectively, that were milked using an automatic milking system, were fed diets containing similar ingredients, and their milk production, plasma metabolites and oxidative status markers were investigated. Dry matter intake and milk yield were not affected by the experimental period. Rectal temperature at 18.00 hours and milk protein concentration in period 1 were higher and lower, respectively, than in period 2 (P < 0.05), suggesting that the hot summer season had an effect on the experimental dairy cows. Plasma glucose and the ascorbic acid + dehydroascorbic acid (AA) concentrations in period 1 were lower than in period 2 (P < 0.01). The plasma malondialdehyde (MDA) concentration did not differ between the experimental periods. The increase in the cellular AA uptake in peripheral tissues in period 1 might be a possible compensatory mechanism to balance the occurrence of reactive oxygen species and the antioxidant capacity in the cells, resulting in the absence of an effect of the hot summer season on plasma MDA concentration. (c) 2016 Japanese Society of Animal Science. PMID- 26800247 TI - Hierarchical MoS2 Nanosheet@TiO2 Nanotube Array Composites with Enhanced Photocatalytic and Photocurrent Performances. AB - A novel type of hierarchical nanocomposites consisted of MoS2 nanosheet coating on the self-ordered TiO2 nanotube arrays is successfully prepared by a facile combination of anodization and hydrothermal methods. The MoS2 nanosheets are uniformly decorated on the tube top surface and the intertubular voids with film appearance changing from brown to black color. Anatase TiO2 nanotube arrays (NTAs) with clean top surfaces and the appropriate amount of MoS2 precursors are key to the growth of perfect compositing TiO2 @MoS2 hybrids with significantly enhanced photocatalytic activity and photocurrent response. These results reveal that the strategy provides a flexible and straightforward route for design and preparation nanocomposites based on functional semiconducting nanostructures with 1D self-ordered TiO2 NTAs, promising for new opportunities in energy/environment applications, including photocatalysts and other photovoltaic devices. PMID- 26800246 TI - Uh and um in children with autism spectrum disorders or language impairment. AB - Atypical pragmatic language is often present in individuals with autism spectrum disorders (ASD), along with delays or deficits in structural language. This study investigated the use of the "fillers" uh and um by children ages 4-8 during the autism diagnostic observation schedule. Fillers reflect speakers' difficulties with planning and delivering speech, but they also serve communicative purposes, such as negotiating control of the floor or conveying uncertainty. We hypothesized that children with ASD would use different patterns of fillers compared to peers with typical development or with specific language impairment (SLI), reflecting differences in social ability and communicative intent. Regression analyses revealed that children in the ASD group were much less likely to use um than children in the other two groups. Filler use is an easy-to quantify feature of behavior that, in concert with other observations, may help to distinguish ASD from SLI. Autism Res 2016, 9: 854-865. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 26800248 TI - The Salmonella In Silico Typing Resource (SISTR): An Open Web-Accessible Tool for Rapidly Typing and Subtyping Draft Salmonella Genome Assemblies. AB - For nearly 100 years serotyping has been the gold standard for the identification of Salmonella serovars. Despite the increasing adoption of DNA-based subtyping approaches, serotype information remains a cornerstone in food safety and public health activities aimed at reducing the burden of salmonellosis. At the same time, recent advances in whole-genome sequencing (WGS) promise to revolutionize our ability to perform advanced pathogen characterization in support of improved source attribution and outbreak analysis. We present the Salmonella In Silico Typing Resource (SISTR), a bioinformatics platform for rapidly performing simultaneous in silico analyses for several leading subtyping methods on draft Salmonella genome assemblies. In addition to performing serovar prediction by genoserotyping, this resource integrates sequence-based typing analyses for: Multi-Locus Sequence Typing (MLST), ribosomal MLST (rMLST), and core genome MLST (cgMLST). We show how phylogenetic context from cgMLST analysis can supplement the genoserotyping analysis and increase the accuracy of in silico serovar prediction to over 94.6% on a dataset comprised of 4,188 finished genomes and WGS draft assemblies. In addition to allowing analysis of user-uploaded whole-genome assemblies, the SISTR platform incorporates a database comprising over 4,000 publicly available genomes, allowing users to place their isolates in a broader phylogenetic and epidemiological context. The resource incorporates several metadata driven visualizations to examine the phylogenetic, geospatial and temporal distribution of genome-sequenced isolates. As sequencing of Salmonella isolates at public health laboratories around the world becomes increasingly common, rapid in silico analysis of minimally processed draft genome assemblies provides a powerful approach for molecular epidemiology in support of public health investigations. Moreover, this type of integrated analysis using multiple sequence-based methods of sub-typing allows for continuity with historical serotyping data as we transition towards the increasing adoption of genomic analyses in epidemiology. The SISTR platform is freely available on the web at https://lfz.corefacility.ca/sistr-app/. PMID- 26800249 TI - Reduction of the Powerful Greenhouse Gas N2O in the South-Eastern Indian Ocean. AB - Nitrous oxide (N2O) is a powerful greenhouse gas and a key catalyst of stratospheric ozone depletion. Yet, little data exist about the sink and source terms of the production and reduction of N2O outside the well-known oxygen minimum zones (OMZ). Here we show the presence of functional marker genes for the reduction of N2O in the last step of the denitrification process (nitrous oxide reductase genes; nosZ) in oxygenated surface waters (180-250 O2 MUmol.kg(-1)) in the south-eastern Indian Ocean. Overall copy numbers indicated that nosZ genes represented a significant proportion of the microbial community, which is unexpected in these oxygenated waters. Our data show strong temperature sensitivity for nosZ genes and reaction rates along a vast latitudinal gradient (32 degrees S-12 degrees S). These data suggest a large N2O sink in the warmer Tropical waters of the south-eastern Indian Ocean. Clone sequencing from PCR products revealed that most denitrification genes belonged to Rhodobacteraceae. Our work highlights the need to investigate the feedback and tight linkages between nitrification and denitrification (both sources of N2O, but the latter also a source of bioavailable N losses) in the understudied yet strategic Indian Ocean and other oligotrophic systems. PMID- 26800250 TI - Life span changes: Performing a continuous 1:2 bimanual coordination task. AB - The experiment was conducted to determine the influence of mirror movements in bimanual coordination during life span. Children, young adults, and older adults were instructed to perform a continuous 1:2 bimanual coordination task by performing flexion-extension wrist movements over 30s where symmetrical and non symmetrical coordination patterns alternate throughout the trial. The vision of the wrists was covered and Lissajous-feedback was provided online. All age groups had to perform 10 trials under three different load conditions (0kg, .5kg, 1.0kg: order counterbalanced). Load was manipulated to determine if increased load increases the likelihood of mirror movements. The data indicated that the performance of the young adults was superior compared to the children and older adults. Children and older adults showed a stronger tendency to develop mirror movements and had particular difficulty in performing the non-symmetrical mode. This type of influence may be attributed to neural crosstalk. PMID- 26800251 TI - The potential of coumatetralyl enhanced by cholecalciferol in the control of anticoagulant-resistant Norway rats (Rattus norvegicus). AB - BACKGROUND: We evaluated the potential of cholecalciferol as an enhancer of the first-generation anticoagulant coumatetralyl in the Westphalia anticoagulant resistant strain of the Norway rat (Rattus norvegicus Berkenhout), characterised by the Tyr139Cys polymorphism on the VKOR enzyme. Because today only the most potent, but also most persistent anticoagulant rodenticides of the second generation remain available to control this strain, new rodenticide solutions are required. RESULTS: Feeding trials in the laboratory confirmed a significant level of efficacy, which was corroborated by field trials in the Munsterland resistance area. After frequency and level of resistance were assessed by blood clotting response tests, field trials were conducted with bait containing coumatetralyl at 375 mg kg-1 and cholecalciferol at 50 mg kg-1 or 100 mg kg-1 . Control success was 94% when a large rat infestation comprising 42% resistant animals was treated. Another field trial applying the combination to a rat population that had survived a preceding treatment with bromadiolone resulted in a 99.5% control success according to the first census day, but with some increase in rat activity during subsequent census days. CONCLUSION: The combination of coumatetralyl and cholecalciferol is a promising alternative approach to the most potent second generation anticoagulants in resistance management, particularly in respect of environmental risks, such as secondary poisoning. (c) 2016 Society of Chemical Industry. PMID- 26800252 TI - Associations between Forkhead Box O1 (FoxO1) Expression and Indicators of Hepatic Glucose Production in Transition Dairy Cows Supplemented with Dietary Nicotinic Acid. AB - Forkhead box protein O1 (FoxO1) is a transcription factor which promotes hepatic glucose production (HGP) by up-regulating the transcription of gluconeogenic enzymes in monogastric species. The activity of FoxO1 is inhibited by insulin induced phosphorylation. The aims of the present study were to find associations between FoxO1 expression and variables associated with HGP as affected by feeding regimen in dairy cows during the transition period. Twenty one healthy German Holstein cows were allocated to four groups (LC-CON, HC-CON, LC-NA with 5 cows/group and HC-NA with 6 cows/group, respectively). Cows received 0 (LC-CON and HC-CON) or 24 (LC-NA and HC-NA) g/d nicotinic acid with high (HC) or low (LC) concentrate proportion from -42 days (-41.8 + 4.8; mean + standard deviation) relative to expected calving date (d-42) to d24. Liver biopsy was taken at d-42, 1, 21, and 100. The total protein expression of FoxO1 (tFoxO1) and the extent of phosphorylation of FoxO1 at serine 256 (pFoxO1) were analysed semiquantitatively by Western Blotting. The expression of hepatic mRNA of FoxO1 and seven genes associated with HGP was measured by real-time RT-PCR. Mixed model and Pearson's correlation were used for statistical evaluation with the level of significance at P<0.05. No dietary effect was observed either on feed intake, energy balance, or on the concentration of blood metabolites. Neither time nor diet affected the expression of FoxO1 total protein and mRNA. A NA * concentrate interaction was found in pFoxO1. However, no corresponding dietary effect was found in the mRNA expression of investigated genes. Different patterns of correlations between FoxO1-related variables and investigated indicators for HGP were found at d21 and 100. The results indicated that the regulation of HGP did not take place on the levels of mRNA and protein expression and the phosphorylation of FoxO1 in dairy cows in early lactation. PMID- 26800253 TI - Recent Advances in Sensing Using Atropoisomeric Molecular Receptors. AB - We describe recent advances in chiroptical chemical sensors, in which the design and implementation is based upon the introduction of atropoisomerically chiral moiety within the molecular skeleton. This report include examples of acyclic, macrocyclic, and polymeric receptors that contain this motif. Although the main applications are in the enantioselective sensing of analytes, we report here some cases where the chiral receptors can in fact be used to senseachiral species. Using circular dichroism (CD) spectroscopy as the technique to detect a receptor analyte interaction, we can distinguish two main sensor categories: that in which the CD signal of a stereolabile, CD-silent probe is activated upon binding, and that in which the signal of a CD-active probe is modulated upon binding. Particular emphasis will be given to cases in which CD spectroscopy is used orthogonally to other means of detection. PMID- 26800254 TI - Chiral, J-Aggregate-Forming Dyes for Alternative Signal Modulation Mechanisms in Self-Immolative Enzyme-Activatable Optical Probes. AB - Enzyme-activatable optical probes are important for future advances in cancer imaging, but may easily suffer from low signal-to-background ratios unless not optimized. To address this shortcoming, numerous mechanisms to modulate the fluorescence signal have been explored. We report herein newly synthesized probes based on self-immolative linkers containing chiral J-aggregate-forming dyes. Signal modulation by formation of chiral J-aggregates is yet unexplored in optical enzyme probe design. The comprehensive characterization of the probes by absorption, CD, fluorescence, and time-resolved fluorescence spectroscopy revealed dye-dye interactions not observed for the free dyes in solution as well as dye-protein interactions with the enzyme. This suggested that J-aggregate formation is challenging to achieve with current probe design and that interactions of the dyes with the enzyme may interfere with achieving high signal to-background ratios. The detailed understanding of the interactions provided herein provides valuable guidelines for the future design of similar probes. PMID- 26800256 TI - Genetic architecture, biochemical underpinnings and ecological impact of floral UV patterning. AB - Floral attraction traits can significantly affect pollinator visitation patterns, but adaptive evolution of these traits may be constrained by correlations with other traits. In some cases, molecular pathways contributing to floral attraction are well characterized, offering the opportunity to explore loci potentially underlying variation among individuals. Here, we quantify the range of variation in floral UV patterning (i.e. UV 'bulls-eye nectar guides) among crop and wild accessions of Brassica rapa. We then use experimental crosses to examine the genetic architecture, candidate loci and biochemical underpinnings of this patterning as well as phenotypic manipulations to test the ecological impact. We find qualitative variation in UV patterning between wild (commonly lacking UV patterns) and crop (commonly exhibiting UV patterns) accessions. Similar to the majority of crops, recombinant inbred lines (RILs) derived from an oilseed crop * WI fast-plant(r) cross exhibit UV patterns, the size of which varies extensively among genotypes. In RILs, we further observe strong statistical-genetic and QTL correlations within petal morphological traits and within measurements of petal UV patterning; however, correlations between morphology and UV patterning are weak or nonsignificant, suggesting that UV patterning is regulated and may evolve independently of overall petal size. HPLC analyses reveal a high concentration of sinapoyl glucose in UV-absorbing petal regions, which, in concert with physical locations of UV-trait QTLs, suggest a regulatory and structural gene as candidates underlying observed quantitative variation. Finally, insects prefer flowers with UV bulls-eye patterns over those that lack patterns, validating the importance of UV patterning in pollen-limited populations of B. rapa. PMID- 26800257 TI - The incidence and sequela of lymphocele formation after robot-assisted extended pelvic lymph node dissection. AB - OBJECTIVE: To determine an accurate incidence of lymphocele formation and its sequela after robot-assisted radical prostatectomy (RARP) and extended lymph node dissection (eLND) in a contemporary prostate cancer cohort. PATIENTS AND METHOD: Consecutive patients who underwent RARP and eLND and had a minimum follow-up of 3 months were included. All surgeries were performed by one surgeon via a transperitoneal approach, with patients uniformly receiving low-molecular-weight heparin. Patients were followed with serial ultrasonography (US) based on a predetermined schedule for lymphocele surveillance. Incidence and sequelae of lymphoceles were retrospectively assessed. RESULTS: In all, 521 patients were analysed. The mean (sd) follow-up was 33.5 (22.8) months. Lymphocele developed in 9% and became symptomatic in 2.5%. All except one were detected at the 1-month postoperative US; however, 76% regressed by the 3-month US. If lymphocele persisted at 3 months, 64% developed symptoms associated with infection and required drainage. Having diabetes mellitus was significantly associated with a higher risk of developing an infected lymphocele. Other symptoms related to lymphocele were rare. Comparisons of patient characteristics between patients with and without lymphoceles did not show any significant prognostic indicators to predict the occurrence of lymphocele in neither univariate nor multivariate analysis in the present cohort. CONCLUSION: The incidence of symptomatic lymphocele after transperitoneal RARP and eLND is rare. However, during follow up, US imaging at 3 months after surgery appears advisable. If a lymphocele is detected at the 3-month follow-up US discussing percutaneous external drainage with the patient appears to be wise, as it may prevent the development of a symptomatic lymphocele in two-thirds of such patients. PMID- 26800259 TI - The Total Synthesis of Inostamycin A. AB - The first total synthesis of inostamycin A is described. With efficient and stereoselective synthetic routes to aldehyde 3 and ketone 4 developed through asymmetric aldol reactions, addition reactions and reduction, and with chiral building blocks, the two large fragments were coupled with remarkable anti stereoselectivity and efficiency by aldol condensation. The coupling reaction provided the complete carbon skeleton with all the requisite functional groups and stereogenic centers for inostamycin A. The two quaternary carbons at C20 and C16 of ketone 4 were elaborated in a highly stereocontrolled manner by addition reactions of the transmetallated 5 to ethyl ketone 6 and the transmetallated 7 to methyl ketone 8, respectively, in which the use of LaCl3 for transmetallation was critical for high coupling efficiency. PMID- 26800260 TI - Chondroid syringoma of the axilla: An unusual tumor diagnosed by fine needle aspiration. AB - Chondroid syringoma (CS) is a rare benign adnexal tumor of the skin with a resemblance to pleomorphic adenoma of salivary gland, most commonly involving the head and neck region. In the present literature, reports of the cytologic appearance of CS are scarce as it is rarely encountered by fine needle aspiration (FNA). A 67-year-old woman presented with a 1 year history of a 1 cm subcutaneous nodule in the right axilla. FNA biopsy was performed revealing an epithelial mesenchymal biphasic neoplasm suggesting CS. Surgical excision confirmed the diagnosis and demonstrated extensive ossification, an extremely rare feature, with only seven reported cases, all located on the head. CS is a rare benign adnexal tumor of the skin, often overlooked due to its unremarkable clinical presentation. FNA is a reliable tool for the diagnosis of CS and helps guide optimal surgical management. PMID- 26800263 TI - Association of Alcohol Misuse With Sexual Identity and Sexual Behavior in Women Veterans. AB - BACKGROUND: Sexual minority women report greater alcohol misuse than heterosexual women in the general population, with more pronounced differences found among younger age groups. It is unknown whether these differences exist among women veterans. OBJECTIVE: We evaluated differences in alcohol misuse across two dimensions of sexual orientation (identity and behavior) among women veterans, and examined whether these differences were modified by age. METHODS: Women veterans were recruited via the internet to participate in an online survey. Participants provided information on their self-reported sexual identity and behavior and responded to the validated 3-item Alcohol Use Disorders Identification Test-Consumption questionnaire (AUDIT-C). Regression models were used to compare the prevalence of alcohol misuse (AUDIT-C >= 3) and severity (AUDIT-C scores) across sexual identity and behavior and to test effect modification by age. RESULTS: Among the 702 participants (36% lesbian/bisexual), prevalence and severity of alcohol misuse varied by both sexual identity and behavior, but there were significant interactions with age. Prevalence and severity of alcohol misuse were higher among relatively younger self-identified lesbians compared to heterosexual women. Similarly, both prevalence and severity of alcohol misuse were generally higher among younger women who had any sex with women compared to those who had sex only with men. CONCLUSIONS/IMPORTANCE: In this online study of women veterans, younger sexual minority women were more likely to screen positive for alcohol misuse, and they had more severe alcohol misuse, than their heterosexual counterparts. Prevention and treatment efforts focused specifically on sexual minority women veterans may be needed. PMID- 26800261 TI - Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. AB - The DNA polymerase and ribonuclease H (RNase H) activities of human immunodeficiency virus type 1 (HIV-1) are needed for the replication of the viral genome and are validated drug targets. However, there are no approved drugs inhibiting RNase H and the efficiency of DNA polymerase inhibitors can be diminished by the presence of drug resistance mutations. In this context, drugs inhibiting both activities could represent a significant advance towards better anti-HIV therapies. We report on the mechanisms of allosteric inhibition of a newly synthesized isatin-based compound designated as RMNC6 that showed IC50 values of 1.4 and 9.8 MUM on HIV-1 RT-associated RNase H and polymerase activities, respectively. Blind docking studies predict that RMNC6 could bind two different pockets in the RT: one in the DNA polymerase domain (partially overlapping the non-nucleoside RT inhibitor [NNRTI] binding pocket), and a second one close to the RNase H active site. Enzymatic studies showed that RMNC6 interferes with efavirenz (an approved NNRTI) in its binding to the RT polymerase domain, although NNRTI resistance-associated mutations such as K103N, Y181C and Y188L had a minor impact on RT susceptibility to RMNC6. In addition, despite being naturally resistant to NNRTIs, the polymerase activity of HIV-1 group O RT was efficiently inhibited by RMNC6. The compound was also an inhibitor of the RNase H activity of wild-type HIV-1 group O RT, although we observed a 6.5-fold increase in the IC50 in comparison with the prototypic HIV-1 group M subtype B enzyme. Mutagenesis studies showed that RT RNase H domain residues Asn474 and Tyr501, and in a lesser extent Ala502 and Ala508, are critical for RMNC6 inhibition of the endonuclease activity of the RT, without affecting its DNA polymerization activity. Our results show that RMNC6 acts as a dual inhibitor with allosteric sites in the DNA polymerase and the RNase H domains of HIV-1 RT. PMID- 26800264 TI - Environmental Stability of Seed Carbohydrate Profiles in Soybeans Containing Different Alleles of the Raffinose Synthase 2 (RS2) Gene. AB - Soybean [Glycine max (L.) Merr.] is important for the high protein meal used for livestock feed formulations. Carbohydrates contribute positively or negatively to the potential metabolizable energy in soybean meal. The positive carbohydrate present in soybean meal consists primarily of sucrose, whereas the negative carbohydrate components are the raffinose family of oligosaccharides (RFOs), raffinose and stachyose. Increasing sucrose and decreasing raffinose and stachyose are critical targets to improve soybean. In three recently characterized lines, variant alleles of the soybean raffinose synthase 2 (RS2) gene were associated with increased sucrose and decreased RFOs. The objective of this research was to compare the environmental stability of seed carbohydrates in soybean lines containing wild-type or variant alleles of RS2 utilizing a field location study and a date of planting study. The results define the carbohydrate variation in distinct regional and temporal environments using soybean lines with different alleles of the RS2 gene. PMID- 26800265 TI - Novel Finding of Widespread Occurrence and Accumulation of Bisphenol A Diglycidyl Ethers (BADGEs) and Novolac Glycidyl Ethers (NOGEs) in Marine Mammals from the United States Coastal Waters. AB - Bisphenol A diglycidyl ether (BADGE)- and bisphenol F diglycidyl ether (BFDGE) based epoxy resins have a broad range of applications, including serving as inner coatings of food and beverage cans and as protective coatings in marine construction. Prior to this study, no studies had examined the occurrence and bioaccumulation of BADGEs or BFDGEs in aquatic organisms. In this study, BADGE, BFDGE, and nine of their derivatives were determined in 121 tissue (liver, kidney, blubber, and brain) samples from eight species of marine mammals collected from the U.S. coastal waters of Florida, California, Washington, and Alaska. BADGE.2HCl was the predominant compound found in the majority (78.5%) of the marine mammal tissues analyzed, at concentrations of up to 2950 ng/g (wet weight (wt)) found in the liver of a sea otter from Kachemak Bay, Alaska. The measured concentrations of BADGE.2HCl in marine mammals were on the order of hundreds of nanograms per gram tissue, which are some of the highest concentrations ever reported for this compound in biota. Males contained greater concentrations of BADGE.2HCl than did females. BADGE.2HCl also was found in the brain tissues of sea otters. Trace levels of BADGE.2HCl were found in the livers of polar bears from Alaska, which suggested that BADGEs are widely distributed in the oceanic environment. PMID- 26800266 TI - Dydrogesterone use in early pregnancy. AB - Successful oocyte implantation and a favorable pregnancy outcome rely on optimal progesterone levels. Therefore, progesterone deficiencies associated with infertility and miscarriage have commonly been treated with progestogens that mimic the activity of progesterone. Among those is dydrogesterone, an oral retrosteroid with a structure closely related to that of progesterone yet with a greater bioavailability and higher selectivity for the progesterone receptor. This review describes the efficacy of dydrogesterone for the treatment of threatened and recurrent miscarriage, and infertility due to luteal phase insufficiency. Data from clinical trials evaluating dydrogesterone in assisted reproductive technology are also discussed. Prospective clinical trials, systematic reviews and meta-analyses have demonstrated that dydrogesterone significantly improves pregnancy outcomes in women with threatened miscarriage or with a history of miscarriage. Although this is not yet a registered indication, dydrogesterone was as effective as vaginal micronized progesterone for luteal phase support in the setting of assisted reproductive technology. The safety and tolerability of dydrogesterone treatment in pregnant women are also briefly addressed and the data support a well-established and favorable benefit-risk profile. PMID- 26800267 TI - Distribution, Fraction, and Ecological Assessment of Heavy Metals in Sediment Plant System in Mangrove Forest, South China Sea. AB - Overlying water, sediment, rhizosphere sediment and mangrove seedlings in the Futian mangrove forest were analyzed for heavy metals. The results showed that mangrove plant acidified sediment and increased organic matter contents. Except for chromium (Cr), nickel (Ni) and copper (Cu) in Aegiceras corniculatum sediment, heavy metals in all sediments were higher than in overlying water, rhizosphere sediment and mangrove root. Heavy metals in Avicennia marina sediments were higher than other sediments. The lower heavy metal biological concentration factors (BCFs) and translocation factors (TFs) indicated that mangrove plant adopted exclusion strategy. The geo-accumulation index, potential ecological risk index and risk assessment code (RAC) demonstrated that heavy metals have posed a considerable ecological risk, especially for cadmium (Cd). Heavy metals (Cr, Ni, Cu and Cd) mainly existed in the reducible fractions. These findings provide actual heavy metal accumulations in sediment-plant ecosystems in mangrove forest, being important in designing the long-term management and conservation policies for managers of mangrove forest. PMID- 26800268 TI - Genetic Characterization of ExPEC-Like Virulence Plasmids among a Subset of NMEC. AB - Neonatal Meningitis Escherichia coli (NMEC) is one of the most common causes of neonatal bacterial meningitis in the US and elsewhere resulting in mortality or neurologic deficits in survivors. Large plasmids have been shown experimentally to increase the virulence of NMEC in the rat model of neonatal meningitis. Here, 9 ExPEC-like plasmids were isolated from NMEC and sequenced to identify the core and accessory plasmid genes of ExPEC-like virulence plasmids in NMEC and create an expanded plasmid phylogeny. Results showed sequenced virulence plasmids carry a strongly conserved core of genes with predicted functions in five distinct categories including: virulence, metabolism, plasmid stability, mobile elements, and unknown genes. The major functions of virulence-associated and plasmid core genes serve to increase in vivo fitness by adding multiple iron uptake systems to the genetic repertoire to facilitate NMEC's survival in the host's low iron environment, and systems to enhance bacterial resistance to host innate immunity. Phylogenetic analysis based on these core plasmid genes showed that at least two lineages of ExPEC-like plasmids could be discerned. Further, virulence plasmids from Avian Pathogenic E. coli and NMEC plasmids could not be differentiated based solely on the genes of the core plasmid genome. PMID- 26800271 TI - Spatial Autocorrelation Approaches to Testing Residuals from Least Squares Regression. AB - In geo-statistics, the Durbin-Watson test is frequently employed to detect the presence of residual serial correlation from least squares regression analyses. However, the Durbin-Watson statistic is only suitable for ordered time or spatial series. If the variables comprise cross-sectional data coming from spatial random sampling, the test will be ineffectual because the value of Durbin-Watson's statistic depends on the sequence of data points. This paper develops two new statistics for testing serial correlation of residuals from least squares regression based on spatial samples. By analogy with the new form of Moran's index, an autocorrelation coefficient is defined with a standardized residual vector and a normalized spatial weight matrix. Then by analogy with the Durbin Watson statistic, two types of new serial correlation indices are constructed. As a case study, the two newly presented statistics are applied to a spatial sample of 29 China's regions. These results show that the new spatial autocorrelation models can be used to test the serial correlation of residuals from regression analysis. In practice, the new statistics can make up for the deficiencies of the Durbin-Watson test. PMID- 26800272 TI - Validating the Rett Syndrome Gross Motor Scale. AB - Rett syndrome is a pervasive neurodevelopmental disorder associated with a pathogenic mutation on the MECP2 gene. Impaired movement is a fundamental component and the Rett Syndrome Gross Motor Scale was developed to measure gross motor abilities in this population. The current study investigated the validity and reliability of the Rett Syndrome Gross Motor Scale. Video data showing gross motor abilities supplemented with parent report data was collected for 255 girls and women registered with the Australian Rett Syndrome Database, and the factor structure and relationships between motor scores, age and genotype were investigated. Clinical assessment scores for 38 girls and women with Rett syndrome who attended the Danish Center for Rett Syndrome were used to assess consistency of measurement. Principal components analysis enabled the calculation of three factor scores: Sitting, Standing and Walking, and Challenge. Motor scores were poorer with increasing age and those with the p.Arg133Cys, p.Arg294* or p.Arg306Cys mutation achieved higher scores than those with a large deletion. The repeatability of clinical assessment was excellent (intraclass correlation coefficient for total score 0.99, 95% CI 0.93-0.98). The standard error of measurement for the total score was 2 points and we would be 95% confident that a change 4 points in the 45-point scale would be greater than within-subject measurement error. The Rett Syndrome Gross Motor Scale could be an appropriate measure of gross motor skills in clinical practice and clinical trials. PMID- 26800273 TI - Bubble CPAP Support after Discontinuation of Mechanical Ventilation Protects Rat Lungs with Ventilator-Induced Lung Injury. AB - BACKGROUND: Bubble continuous positive airway pressure (BCPAP) has been used in neonates with respiratory distress for decades, but its lung-protective effect and underlying mechanism has not been investigated. OBJECTIVES: To test the hypothesis that BCPAP use after extubation decreases lung injury and that alterations to lung nitric oxide synthase (NOS) 3 expression may be one of the underlying mechanisms. METHODS: We compared gas exchange, lung injury severity, and lung NOS expression among rats with ventilator-induced lung injury (VILI) treated with either BCPAP or spontaneous breathing. After high tidal volume ventilation for 30 min, the rats were randomly divided to three groups: a control group underwent spontaneous breathing (n = 7), and two BCPAP groups were treated with the bubble technique with either a 2.5-mm-diameter (n = 7) or a 5.5-mm diameter (n = 7) expiratory limb for 2 h. RESULTS: The bubble technique (2.5 and 5.5 mm diameter combined) resulted in a significantly higher PaO2, decreased alveolar protein levels (1.01 vs. 1.43 mg/kg, p < 0.05), a lower lung injury score (3.87 vs. 4.86, p < 0.05), and decreased NOS3 expression (1.99 vs. 3.32, p < 0.05) compared to spontaneous breathing in the control group. BCPAP with a 2.5 mm-diameter and with a 5.5-mm-diameter expiratory limb was not different with regard to gas exchange, alveolar protein levels, and lung injury scores, but there was a trend for lower NOS3 expression in the 5.5-mm group (1.41 vs. 2.56, p = 0.052). CONCLUSIONS: BCPAP decreases lung injury in rats with VILI after stopping mechanical ventilation. Attenuation of lung NOS3 expression may be one of the underlying mechanisms. PMID- 26800274 TI - Artificial Water Point for Livestock Influences Spatial Ecology of a Native Lizard Species. AB - Pastoralism is a major agricultural activity in drier environments, and can directly and indirectly impact native species in those areas. We investigated how the supply of an artificial watering point to support grazing livestock affected movement and activity patterns of the Australian sleepy lizard (Tiliqua rugosa) during a drought year. We observed 23 adult lizards; six had access to a dam, whereas 17 lizards did not. Lizards with access to the dam had larger home ranges, were substantially active on more days (days with >100 steps), and moved more steps per day compared to lizards that did not have access to the dam, both during the early and late period of our observation. Furthermore, while the two groups of lizards had similar body condition early in the season, they differed later in the season. Lizards with dam access retained, whereas lizards without access lost body condition. Local heterogeneity in access to an artificial water resource resulted in spatially dependent behavioural variation among sleepy lizard individuals. This suggests that sleepy lizards have flexible responses to changing climatic conditions, depending on the availability of water. Furthermore, while reducing activity appears a suitable short term strategy, if harsh conditions persist, then access to dams could be of substantial benefit and could support sustained lizard activity and movement and allow maintenance of body condition. Hence, artificial watering points, such as the dams constructed by pastoralists, may provide local higher quality refugia for sleepy lizards and other species during drought conditions. PMID- 26800275 TI - Shifting the Paradigm: Adolescent Cannabis Abuse and the Need for Early Intervention. AB - This article describes the increasing risks of use of marijuana and related products by adolescents. As THC content increases and methods such as "dabbing" increase frequency of use, risks of marijuana use as perceived by youth are decreasing. At a time when marijuana access is increasing nationally, a new marijuana landscape is forming in which both adolescents and treatment providers must adjust their perceptions of what was once thought of as a "harmless" drug. This article describes this new landscape, and what it may mean for adolescent drug treatment. PMID- 26800277 TI - Urinary incontinence in men: current and developing therapy options. AB - INTRODUCTION: Urinary incontinence in men is a significant and often underappreciated problem. Men can have urgency and or stress incontinence. Urgency incontinence as part of the overactive bladder (OAB) syndrome and can often coexist with benign prostatic obstruction (BPO) in men and the initial treatment of this is conservative lifestyle changes and then medical therapy. AREAS COVERED: This literature review aims to cover synthetic drugs currently utilised to treat urinary incontinence in men that are phase III and onwards. Neurological incontinence and surgical treatment options for male urinary incontinence are beyond the scope of this review. EXPERT OPINION: The most common form of urinary incontinence in men is urgency incontinence secondary to an OAB, which often co-exists in men, with bladder outflow obstruction (BOO). The pharmacotherapy options to treat OAB include antimuscarinics, beta3 agonists and phosphodiesterase inhibitors. Antimuscarinics and beta3 agonists are effective in treating OAB, and have been found to have no increased urinary retention risk in the group of patients with co-existing BPO. Emerging medications include the alternative beta3 agonists - solabegron and ritobegron. The future may include novel combinations of these therapies. PMID- 26800278 TI - Austrobdella cairae n. sp., an Oioxenous Marine Leech (Clitellata: Piscicolidae) from the Banded Guitarfish, Zapteryx exasperata, in the Northeastern Pacific Ocean. AB - A new marine leech is herein described from specimens infecting the external surfaces, including the mouth and cloaca, of the banded guitarfish, Zapteryx exasperate, captured in the Gulf of California and eastern Pacific Ocean off the coast of San Diego, California. The leech is assigned to Austrobdella by possessing continuous contractile coelomic channels that lie outside the somatic musculature along the lateral edges of the urosome (marginal lacunae), clitellar gland cells densely packed in the urosome, 5 pairs of testisacs, and 6-annulate mid-body somites. The new leech is distinguished from its 6 congeners on the basis of body size (maximum 10 mm long) and shape (sub-cylindrical trachelosome distinctly demarcated from wider urosome that is ventrally flattened, convex dorsally, and narrowing toward caudal sucker that is narrow, 20-25% of maximum body width), number of eyespots (2 pairs), shape and arrangement of the ovisacs (pyriform and limited to somites XII/XIII), and characteristics of the midgut (1 pair of mycetomes, 6 pairs of simple thin-walled crop ceca, ventral postceca wanting, and 2 pairs of dendritic diverticula emerging from anterior portion of thick-walled intestine). The new species occurs in the northeastern Pacific Ocean on a benthic elasmobranch. Examination of host specificity for each Austrobdella species using the quantitative Index of Phylogenetic Host Specificity revealed that the new species is 1 of 4 oioxenous specialists in the genus, and the remaining 3 congeners are relative generalists herein classified as euryxenous. This is the first time host specificity for members of the Piscicolidae has been quantitatively assessed. The analysis suggests that associations between marine leeches belonging in Austrobdella and their vertebrate hosts are driven by ecological influences rather than host taxonomic placement. PMID- 26800279 TI - Electron Transfer Rate Maxima at Large Donor-Acceptor Distances. AB - Because of their low mass, electrons can transfer rapidly over long (>15 A) distances, but usually reaction rates decrease with increasing donor-acceptor distance. We report here on electron transfer rate maxima at donor-acceptor separations of 30.6 A, observed for thermal electron transfer between an anthraquinone radical anion and a triarylamine radical cation in three homologous series of rigid-rod-like donor-photosensitizer-acceptor triads with p-xylene bridges. Our experimental observations can be explained by a weak distance dependence of electronic donor-acceptor coupling combined with a strong increase of the (outer-sphere) reorganization energy with increasing distance, as predicted by electron transfer theory more than 30 years ago. The observed effect has important consequences for light-to-chemical energy conversion. PMID- 26800281 TI - Flavonol-carbon nanostructure hybrid systems: a DFT study on the interaction mechanism and UV/Vis features. AB - Flavonols are a class of natural compounds with potential biological and pharmacological applications. They are also natural pigments responsible for the diversity of colors in plants. Flavonols offer the possibility of tuning their features through chemical functionalization as well as the presence of an aromatic backbone, which could lead to non-covalent interactions with different nanostructures or aromatic molecules. In this work, a protocol based on ONIOM (QM/QM) calculations to investigate the structural features (binding energies, intermolecular interactions) of flavonols interacting with the surface of several carbon nanostructures (such as graphene, fullerene C60 and carbon nanotubes) is developed. The confinement of flavonols inside carbon nanotubes has also been studied. Three flavonols, galangin, quercetin and myricetin, as well as pristine flavone were selected. Special attention has also been paid to the changes in UV/Vis features of flavonols due to the interaction with carbon nanostructures. Our results point out that pi-stacking interactions are the driving force for the adsorption onto carbon nanostructures as well as for the confinement inside carbon nanotubes. Likewise, UV/Vis features of flavonols could be fine-tuned through the interaction with suitable carbon nanostructures. PMID- 26800280 TI - Repeatability and sensitivity of T2* measurements in patients with head and neck squamous cell carcinoma at 3T. AB - PURPOSE: To determine whether quantitation of T2* is sufficiently repeatable and sensitive to detect clinically relevant oxygenation levels in head and neck squamous cell carcinoma (HNSCC) at 3T. MATERIALS AND METHODS: Ten patients with newly diagnosed locally advanced HNSCC underwent two magnetic resonance imaging (MRI) scans between 24 and 168 hours apart prior to chemoradiotherapy treatment. A multiple gradient echo sequence was used to calculate T2* maps. A quadratic function was used to model the blood transverse relaxation rate as a function of blood oxygenation. A set of published coefficients measured at 3T were incorporated to account for tissue hematocrit levels and used to plot the dependence of fractional blood oxygenation (Y) on T2* values, together with the corresponding repeatability range. Repeatability of T2* using Bland-Altman analysis, and calculation of limits of agreement (LoA), was used to assess the sensitivity, defined as the minimum difference in fractional blood oxygenation that can be confidently detected. RESULTS: T2* LoA for 22 outlined tumor volumes were 13%. The T2* dependence of fractional blood oxygenation increases monotonically, resulting in increasing sensitivity of the method with increasing blood oxygenation. For fractional blood oxygenation values above 0.11, changes in T2* were sufficient to detect differences in blood oxygenation greater than 10% (Delta T2* > LoA for DeltaY > 0.1). CONCLUSION: Quantitation of T2* at 3T can detect clinically relevant changes in tumor oxygenation within a wide range of blood volumes and oxygen tensions, including levels reported in HNSCC. J. Magn. Reson. Imaging 2016;44:72-80. PMID- 26800283 TI - Novel Asymmetric Wettable AgNPs/Chitosan Wound Dressing: In Vitro and In Vivo Evaluation. AB - A novel silver nanoparticles (AgNPs)/chitosan composite dressing with asymmetric wettability surfaces was successfully prepared via a simple two-step method for biomedical applications as wound healing materials. First, AgNPs were assembled into the chitosan sponge which was prepared by lyophilization process. Then one side of the sponge was modified by a thin layer of stearic acid. The incorporation of AgNPs into chitosan dressing could enhance the antibacterial activity against drug-sensitive and drug-resistant pathogenic bacteria. The asymmetric surface modification endows the dressing with both highly hydrophobic property and inherent hydrophilic nature of chitosan. The hydrophobic surface of the dressing shows waterproof and antiadhesion for contaminant properties, whereas the hydrophilic surface preserves its water-absorbing capability and efficiently inhibits the growth of bacteria. Furthermore, the AgNPs/chitosan composite dressing displays improved moisture retention and blood clotting ability compared to the unmodified dressings. Cytocompatibility test evaluated in vitro and in a wound infection model illustrates the nontoxic nature of the composite dressing. More importantly, the in vivo wound healing model evaluation in mice reveals that the asymmetric AgNPs/chitosan dressing promotes the wound healing and accelerates the reepithelialization and collagen deposition. The silver accumulation in mice body treated by the composite dressing is far lower than that of the clinically used Acasin nanosilver dressing treated mice. This work indicates the huge potential of the novel AgNPs/chitosan wound dressing with asymmetrical wettability for clinical use. PMID- 26800285 TI - A tribute to Alton David Floyd July 17, 1941-October 29, 2015. PMID- 26800284 TI - Salivary and serum procalcitonin and C-reactive protein as biomarkers of periodontitis in United States veterans with osteoarthritis or rheumatoid arthritis. AB - Serum procalcitonin (ProCT) is elevated in response to bacterial infections, whereas high sensitivity C-reactive protein (hsCRP) is a nonspecific inflammatory marker that is increased by excess adipose tissue. We examined the efficacy of ProCT and hsCRP as biomarkers of periodontitis in the saliva and serum of patients with arthritis, which is characterized by variable levels of systemic inflammation that potentially can confound the interpretation of inflammatory biomarkers. Blood and unstimulated whole saliva were collected from 33 patients with rheumatoid arthritis (RA) and 50 with osteoarthritis (OA). Periodontal status was assessed by full mouth examination and patients were categorized as having no/mild, moderate or severe periodontitis by standard parameters. Salivary and serum ProCT and hsCRP concentrations were compared. BMI, diabetes, anti inflammatory medications and smoking status were ascertained from the patient records. Differences between OA and RA in proportionate numbers of patients were compared for race, gender, diabetes, adiposity and smoking status. Serum ProCT was significantly higher in arthritis patients with moderate to severe and severe periodontitis compared with no/mild periodontitis patients. There were no significant differences in salivary ProCT or salivary or serum hsCRP in RA patients related to periodontitis category. Most of the OA and RA patients were middle aged or older, 28.9% were diabetic, 78.3% were overweight or obese, and slightly more than half were either current or past smokers. The OA and RA groups differed by race, but not gender; blacks and males were predominant in both groups. The OA and RA groups did not differ in terms of controlled or uncontrolled diabetes, smoking status or BMI. The RA patients had been prescribed more anti-inflammatory medication than the OA patients. Our results demonstrate that circulating ProCT is a more discriminative biomarker for periodontitis than serum hsCRP in patients with underlying arthritis. Any elevation in salivary and serum hsCRP due to periodontitis apparently was overshadowed by differences among these patients in factors that influence CRP, such as the extent of inflammation between RA and OA, the extent of adipose tissue, the use of anti- inflammatory medications and smoking status. Although our study showed no differences in salivary ProCT related to severity of periodontitis, this biomarker also may be useful with further refinement. PMID- 26800289 TI - Fullrmc, a rigid body Reverse Monte Carlo modeling package enabled with machine learning and artificial intelligence. AB - A new Reverse Monte Carlo (RMC) package "fullrmc" for atomic or rigid body and molecular, amorphous, or crystalline materials is presented. fullrmc main purpose is to provide a fully modular, fast and flexible software, thoroughly documented, complex molecules enabled, written in a modern programming language (python, cython, C and C++ when performance is needed) and complying to modern programming practices. fullrmc approach in solving an atomic or molecular structure is different from existing RMC algorithms and software. In a nutshell, traditional RMC methods and software randomly adjust atom positions until the whole system has the greatest consistency with a set of experimental data. In contrast, fullrmc applies smart moves endorsed with reinforcement machine learning to groups of atoms. While fullrmc allows running traditional RMC modeling, the uniqueness of this approach resides in its ability to customize grouping atoms in any convenient way with no additional programming efforts and to apply smart and more physically meaningful moves to the defined groups of atoms. In addition, fullrmc provides a unique way with almost no additional computational cost to recur a group's selection, allowing the system to go out of local minimas by refining a group's position or exploring through and beyond not allowed positions and energy barriers the unrestricted three dimensional space around a group. PMID- 26800290 TI - Alstoscholarisines H-J, Indole Alkaloids from Alstonia scholaris: Structural Evaluation and Bioinspired Synthesis of Alstoscholarisine H. AB - Alstoscholarisines H-J (1-3), new monoterpenoid indole alkaloids with an unprecedented skeleton created via the formation of a C-3/N-1 bond, were isolated from Alstonia scholaris. Their structures were established by extensive spectroscopic analyses and the assessment of single-crystal X-ray diffraction data. The total synthesis of alstoscholarisine H was achieved via the regioselective nucleophilic addition of pyridinium through a bioinspired iminium ion intermediate followed by Pictet-Spengler-like cyclization. PMID- 26800292 TI - Early and late vulval cancer recurrences: Are they different? AB - Vulval cancers are rare, but after primary treatment, known to recur with a high frequency (30%). Clinico-pathological predictors of recurrence have been established to a great extent. However, there is paucity of literature on predictors of early versus late recurrence. We sought to identify such predictors through a retrospective study of vulval cancer recurrences in a single cancer centre over 11 years. Age of women, depth of invasion/site of primary tumour and presence of background VIN/lichen sclerosus do not appear to affect timing of recurrence. However, vulval cancers that recur after 2 years of primary tumour recognition are more likely to be well-differentiated tumours, have undergone radical surgery and have had a closest disease-free margin >1 cm. Late recurrences are entirely local rather than distant metastases and this translates into a better survival as shown in our study (40 months median survival in the early group versus 112 in the late recurrence group). PMID- 26800293 TI - Should MRI be the primary endpoint of phase 3 trials in multiple sclerosis? PMID- 26800296 TI - Patch esophagoplasty with a free proximal lateral leg flap for focal stricture of the cervical esophagus: A case report. AB - Esophageal stricture after surgery or trauma is a major reason for poor oral nutrition, body-weight loss, and general damage to health. Patch esophagoplasty, after repeated failed dilation attempts, is recommended for focal esophageal strictures. In this report, we present a case in which a free proximal lateral leg flap was used for reconstruction of focal stricture of the cervical esophagus. A 62-year-old man developed progressive dysphagia after hypopharyngeal cancer ablation and adjuvant radiotherapy. He was referred for surgical interventions after repeated failed dilation attempts. Preoperative evaluation revealed a 3-cm segment stricture of the cervical esophagus without evidence of an additional distal stricture. Patch esophagoplasty with free tissue transfer was planned. After the stricture site had been explored, the fibrotic tissue was resected. A pathology report confirmed no evidence of malignancy. The resultant defect in an otherwise healthy posterior esophageal wall was reconstructed using a proximal lateral leg flap. Recovery was uneventful and the functional outcome was satisfactory at the 6-month follow-up. For the radiated patients with cervical esophageal focal strictures, we introduced a novel use of the proximal lateral leg flap in patch esophagoplasty because of its unnoticeable donor site morbidity and its thin and pliable nature. (c) 2016 Wiley Periodicals, Inc. Microsurgery 37:426-430, 2017. PMID- 26800297 TI - Modulated Binary-Ternary Dual Semiconductor Heterostructures. AB - A generic modular synthetic strategy for the fabrication of a series of binary ternary group II-VI and group I-III-VI coupled semiconductor nano heterostructures is reported. Using Ag2 Se nanocrystals first as a catalyst and then as sacrificial seeds, four dual semiconductor heterostructures were designed with similar shapes: CdSe-AgInSe2 , CdSe-AgGaSe2 , ZnSe-AgInSe2 , and ZnSe AgGaSe2 . Among these, dispersive type-II heterostructures are further explored for photocatalytic hydrogen evolution from water and these are observed to be superior catalysts than the binary or ternary semi-conductors. Details of the chemistry of this modular synthesis have been studied and the photophysical processes involved in catalysis are investigated. PMID- 26800298 TI - Molecular dynamics simulations of apo, holo, and inactivator bound GABA-at reveal the role of active site residues in PLP dependent enzymes. AB - The pyridoxal 5-phosphate (PLP) cofactor is a significant organic molecule in medicinal chemistry. It is often found covalently bound to lysine residues in proteins to form PLP dependent enzymes. An example of this family of PLP dependent enzymes is gamma-aminobutyric acid aminotransferase (GABA-AT) which is responsible for the degradation of the neurotransmitter GABA. Its inhibition or inactivation can be used to prevent the reduction of GABA concentration in brain which is the source of several neurological disorders. As a test case for PLP dependent enzymes, we have performed molecular dynamics simulations of GABA-AT to reveal the roles of the protein residues and its cofactor. Three different states have been considered: the apoenzyme, the holoenzyme, and the inactive state obtained after the suicide inhibition by vigabatrin. Different protonation states have also been considered for PLP and two key active site residues: Asp298 and His190. Together, 24 independent molecular dynamics trajectories have been simulated for a cumulative total of 2.88 us. Our results indicate that, unlike in aqueous solution, the PLP pyridine moiety is protonated in GABA-AT. This is a consequence of a pKa shift triggered by a strong charge-charge interaction with an ionic "diad" formed by Asp298 and His190 that would help the activation of the first half-reaction of the catalytic mechanism in GABA-AT: the conversion of PLP to free pyridoxamine phosphate (PMP). In addition, our MD simulations exhibit additional strong hydrogen bond networks between the protein and PLP: the phosphate group is held in place by the donation of at least three hydrogen bonds while the carbonyl oxygen of the pyridine ring interacts with Gln301; Phe181 forms a pi-pi stacking interaction with the pyridine ring and works as a gate keeper with the assistance of Val300. All these interactions are hypothesized to help maintain free PMP in place inside the protein active site to facilitate the second half-reaction in GABA-AT: the regeneration of PLP-bound GABA-AT (i.e., the holoenzyme). Proteins 2016; 84:875-891. (c) 2016 Wiley Periodicals, Inc. PMID- 26800299 TI - The Effect of the 2009 U.S. Preventive Services Task Force Breast Cancer Screening Recommendations on Mammography Rates. AB - OBJECTIVE: To examine the effect of a change in U.S. Preventive Services Task Force (USPSTF) screening guidelines on mammography rates in the United States. PRINCIPAL FINDINGS: In 2010, the year following the change in guidelines, 12 month mammography prevalence among women aged 40-49 years fell by 2.09 percentage points (95 percent confidence interval [CI]: -2.87 to -1.31) from 54.63 percent in 2008. For women aged 50-74 years, and aged 75 years and older, 12-month screening rates were 2.21 (95 percent CI: -2.65 to -1.77) and 3.60 (95 percent CI: -4.48 to -2.70) percentage points lower than those in 2008. In 2012, for women aged 40-49 years, 12-month prevalence fell to 52.51 percent, a decline of 2.12 percentage points (95 percent CI: -2.79 to -1.32) relative to screening rates prior the USPSTF announcement. For women aged 50-74 years and aged 75 years and older screening rates were 2.45 (95 percent CI: -2.96 to -2.07) and 5.71 (95 percent CI: -6.61 to -4.81) percentage points lower, respectively, in 2012 than in 2008. CONCLUSION: This study demonstrates an immediate and lasting reduction in the rates of breast cancer screening among women of all age groups after the 2009 revision of screening guidelines by the USPSTF. PMID- 26800301 TI - Decreases in ganglion cell layer and inner plexiform layer volumes correlate better with disease severity in schizophrenia patients than retinal nerve fiber layer thickness: Findings from spectral optic coherence tomography. AB - BACKGROUND: Optic coherence tomography (OCT) is a new, contactless and fast neuroimaging method. Previous studies have observed thinning of the retinal nerve fibre layer (RNFL) in many neurodegenerative diseases, and researchers have suggested that correlations exist between the thinning of the RNFL and the neurodegeneration detected with other imaging methods or the severity of illness. More recently, OCT has been used in patients with schizophrenia. RNFL thinning has also been detected in these patients. With more sophisticated devices, segmentation of the retina and measurements of the ganglion cell layer (GCL) and internal plexiform layer (IPL) can be performed. METHODS: We measured the RNFL thickness and the GCL and IPL volumes in 40 treatment refractory patients with schizophrenia, 41 treatment responsive refractory patients and 41 controls using spectral-OCT, and we evaluated the correlations between the disease severity and OCT measurements. RESULTS: The global RNFL thickness and GCL and IPL volumes were decreased in the patients with schizophrenia compared with the controls. In addition, the GCL and IPL volumes were lower in the treatment refractory patients with schizophrenia compared to the treatment responsive patients. Using parameters such as the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) scores, the disease duration and number of hospitalizations, correlations between the GCL and IPL volumes and disease severity were stronger than the correlations between the RNFL and the disease parameters. CONCLUSION: Our findings suggest that OCT can be used to detect neurodegeneration in schizophrenia and that the GCL and IPL volumes can also be used to monitor the progression of neurodegeneration. PMID- 26800302 TI - Dynamics of salivary cortisol in chronic kidney disease patients at stages 1 through 4. AB - CONTEXT: End-stage renal disease has been associated with derangement of the HPA function. The dynamics of this axis in early stages of renal disease (CKD) has not been assessed. OBJECTIVES: To evaluate in patients with CKD at stages 1-4 (KDOQI): the diurnal variation of salivary cortisol; the suppressibility of cortisol in saliva and serum after an overnight oral 1 mg dexamethasone suppression test (1 mg DST) with simultaneous measurement of circulating dexamethasone. DESIGN AND METHODS: 80 CKD outpatients and 40 healthy subjects were included. All CKD collected whole saliva at 08.00 and 23.00 h (SAF23 ) on two nonconsecutive days. Thereafter at 08.00 h, following 1 mg DST, saliva and blood were obtained. Salivary and serum cortisol as well as CBG were assessed by RIA, dexamethasone by ELISA and serum free cortisol was calculated. RESULTS: SAF23 correlated negatively with glomerular filtration rate (GFR). The fraction of free cortisol in serum and saliva after 1 mg DST, correlated positively and significantly in both patients with CKD and healthy subjects (r: 0.86 and r: 0.85, respectively; P < 0.0001 for both). Ten percent of CKD with GFR < 90 ml/min/1.73 m(2) had false positive results unrelated to dexamethasone and CBG concentrations. CONCLUSIONS: False positive responses to 1 mg DST were associated with GFR < 90 ml/min/1.73 m(2) . This could not be ascribed to either defects in dexamethasone absorption or CBG concentrations. Higher dexamethasone doses were necessary to achieve adequate HPA suppression. Salivary cortisol was useful to assess circadian cortisol levels and feed-back regulation in CKD. PMID- 26800304 TI - Non-invasive measurement of abnormal ventilatory mechanics in amyotrophic lateral sclerosis. AB - INTRODUCTION: In this study we investigated non-invasive, effort-independent measurement of ventilatory mechanics in patients with amyotrophic lateral sclerosis (ALS). METHODS: Ventilatory mechanics were measured by optoelectronic plethysmography (OEP) in ALS patients and matched controls. Analysis determined whether OEP measurements correlated with standard clinical measures. RESULTS: ALS patients (N = 18) had lower forced vital capacity percent predicted (55.2 +/- 22.0 L) compared with controls (N = 15; 104.7 +/- 16.2 L) and higher ventilatory inefficiency (49.2 +/- 9.0 vs. 40.0 +/- 3.5, respectively; P < 0.001 for both measures). Lower tidal volumes within the diaphragm area correlated with the dyspnea subscore calculated from the ALS Functional Rating Scale-revised (P = 0.031), and paradoxical movement of the ribcage compared with the abdominal compartment was seen in the most severe cases. CONCLUSIONS: Evaluation of ventilatory mechanics in mild to severe ALS reveals dysfunction that is not readily detected by standard testing and ALS functional severity assessment measures. Muscle Nerve 54: 270-276, 2016. PMID- 26800305 TI - A pilot study of a combined group and individual functional remediation program for patients with bipolar I disorder. AB - BACKGROUND: Bipolar disorder has been associated with a decrease in cognitive functioning affecting the functional outcome of patients independent of mood states. However, there have only been few attempts to investigate the effects of functional remediation for patients with bipolar disorder. The current study investigates the feasibility and effectiveness of a combined group and individual functional remediation program for bipolar disorder, including both patients and their caregivers. METHODS: Twelve participants diagnosed with bipolar I disorder, and their caregivers, were treated with a combined group and individual functional remediation program. The feasibility of the program was evaluated by dropout rates and participants' evaluations of the program. The effectiveness of the program was explored through the assessment of functional outcome at baseline, immediately post-treatment, and follow-up three months later. RESULTS: The results indicate a high degree of satisfaction and a low dropout rate with the current program. Assessment of outcomes suggests improved functioning in the areas of autonomy and occupational functioning, evolving from baseline to follow up. LIMITATIONS: Due to a small sample size and the lack of a control group the results are preliminary. CONCLUSIONS: This relatively brief intervention offers a more tailor-made approach to functional remediation and shows good feasibility, acceptability and improvement of functioning in patients with bipolar I disorder. PMID- 26800306 TI - Post-GWAS methodologies for localisation of functional non-coding variants: ANGPTL3. AB - Genome-wide association studies have confirmed the involvement of non-coding angiopoietin-like 3 (ANGPTL3) gene variants with coronary artery disease, levels of low-density lipoprotein cholesterol (LDL-C), triglycerides and ANGPTL3 mRNA transcript. Extensive linkage disequilibrium at the locus, however, has hindered efforts to identify the potential functional variants. Using regulatory annotations from ENCODE, combined with functional in vivo assays such as allele specific formaldehyde-assisted isolation of regulatory elements, statistical approaches including eQTL/lipid colocalisation, and traditional in vitro methodologies including electrophoretic mobility shift assay and luciferase reporter assays, variants affecting the ANGPTL3 regulome were examined. From 253 variants associated with ANGPTL3 mRNA expression, and/or lipid traits, 46 were located within liver regulatory elements and potentially functional. One variant, rs10889352, demonstrated allele-specific effects on DNA-protein interactions, reporter gene expression and chromatin accessibility, in line with effects on LDL C levels and expression of ANGPTL3 mRNA. The ANGPTL3 gene lies within DOCK7, although the variant is within non-coding regions outside of ANGPTL3, within DOCK7, suggesting complex long-range regulatory effects on gene expression. This study illustrates the power of combining multiple genome-wide datasets with laboratory data to localise functional non-coding variation and provides a model for analysis of regulatory variants from GWAS. PMID- 26800307 TI - LDL accelerates monocyte to macrophage differentiation: Effects on adhesion and anoikis. AB - BACKGROUND AND AIMS: High LDL triggers dyslipidemia and atherosclerosis, a chronic inflammatory disease with participation of the innate immunity system. Monocytes are recruited to areas of LDL-induced endothelial damage and initiate differentiation. This study was aimed to investigate the effects of LDL on the early transitional stages of monocyte differentiation into macrophages. METHODS: Blood monocytes, isolated from healthy donors by their adhesion properties, were exposed to native-LDL (1.80 mg/mL) for 48-h. Monocyte phenotype was assessed at transcript and miRNA levels by real-time PCR. Protein-expression was determined by western-blot and flow-cytometry. RESULTS: CD14 time-dependently decreased in adhered monocytes, reaching a >4 fold decrease at transcript- and protein-levels after 7-days in culture when cells were already differentiated into macrophages. At 4-days differentiation, monocytes exposed to LDL reduced CD14-transcrition >1.5 fold in mRNA (p = 0.002) and 34% CD14-protein (p = 0.039), whereas increased in CD16-expression (p = 0.019). Besides, LDL induced a significant increase in integrin CD49c (alpha3-subunit) at mRNA (>2 fold, p = 0.008) and protein (>3 fold, p = 0.045) level and a decrease in the apoptosis-effectors CASP8 and CASP3 (p = 0.002 and p = 0.035, respectively) as well as in the precursor form of the death-receptor DR5 (p = 0.045) without affecting its mRNA-expression level, suggesting a LDL-dependent post-transcriptional regulation of DR5. In silico prediction analysis indicated miR-126-3p as a candidate to regulate DR5 expression and miR-126-3p was shown affected by LDL reaching a significant increase (p = 0.033). CONCLUSIONS: In differentiating human monocytes, LDL stimulates expression of cell-adhesion molecules and downregulates apoptosis effectors, regulating anoikis and survival programs in the early stage macrophages. PMID- 26800308 TI - The relation between apolipoprotein E (APOE) genotype and peripheral artery disease in patients at high risk for cardiovascular disease. AB - INTRODUCTION: The apolipoprotein E gene (APOE) is associated with coronary heart disease and stroke, but the relation with peripheral artery disease (PAD) is unknown. We investigated the relation of APOE genotype with PAD and other types of vascular disease. METHODS: The cross-sectional association between APOE genotype and ankle-brachial index (ABI) and vascular disease prevalence; and the prospective relation with incident PAD and other types of vascular disease (coronary artery disease, stroke and vascular mortality) were evaluated in 7418 patients from the Secondary Manifestations of ARTerial disease (SMART) study. This is a prospective cohort study in patients with cardiovascular disease or a cardiovascular risk factor. Analyses were adjusted for age and sex. RESULTS: Mean age was 56.7 +/- 12.4 years and 68% of the patients was male. APOE genotype frequencies were epsilon2epsilon2 1.3%; epsilon2epsilon3 9.9%; epsilon2epsilon4 2.4%; epsilon3epsilon3 56.9%; epsilon3epsilon4 26.7% and epsilon4epsilon4 2.8%. Median follow-up time was 8.1 years (IQR 5.4-11.4) in which 452 new PAD events occurred. The epsilon2epsilon2 genotype was significantly associated with a lower ABI (regression coefficient -0.04, 95%CI -0.07 to -0.01), increased PAD prevalence (prevalence ratio 1.54, 95%CI 1.01-2.17) and a higher risk of incident PAD (HR 2.31, 95%CI 1.29-4.12) compared with epsilon3epsilon3. No relations between APOE genotypes and other vascular disease were observed. CONCLUSION: Of the six APOE genotypes, the epsilon2epsilon2 variant is associated with an increased risk for PAD in patients at high risk for cardiovascular disease. No association was observed between APOE genotype and coronary artery disease, stroke or vascular mortality in this population. PMID- 26800309 TI - Discovery of Narrow Spectrum Kinase Inhibitors: New Therapeutic Agents for the Treatment of COPD and Steroid-Resistant Asthma. AB - The discovery of a novel series of therapeutic agents that has been designed and optimized for treating chronic obstructive pulmonary disease is reported. The pharmacological strategy was based on the identification of compounds that inhibit a defined subset of kinase enzymes modulating inflammatory processes that would be effective against steroid refractory disease and exhibit a sustained duration of action after inhaled delivery. PMID- 26800310 TI - The battle for survival between viruses and their host plants. AB - Evolution has equipped plants with defense mechanisms to counterattack virus infections. However, some viruses have acquired the capacity to escape these defense barriers. In their combats, plants use mechanisms such as antiviral RNA silencing that viruses fight against using silencing-repressors. Plants could also resist by mutating a host factor required by the virus to complete a particular step of its infectious cycle. Another successful mechanism of resistance is the hypersensitive response, where plants engineer R genes that recognize specifically their assailants. The recognition is followed by the triggering of a broad spectrum resistance. New understanding of such resistance mechanisms will probably helps to propose new means to enhance plant resistance against viruses. PMID- 26800311 TI - De novo CD5+ diffuse large B-cell lymphoma: Adverse outcomes with and without stem cell transplantation in a large, multicenter, rituximab treated cohort. AB - De novo CD5+ diffuse large B-cell lymphomas (DLBCL) are a distinct subgroup of DLBCL with poor prognosis. However the role of rituximab-containing therapy and salvage stem cell transplantation in this patients' population remain to be defined. We retrospectively reviewed clinical features and outcomes of 102 patients with de novo CD5+ DLBCL treated with rituximab-containing therapy at nine different institutions. By Hans' criteria, 64 patients had activated B-cell (ABC) subtype, 24 germinal center B-cell (GCB) subtype, and 14 were not evaluated. No patients had a myc translocation. Eighty-three patients were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R CHOP), 7 with rituximab, etoposide, cyclophosphamide, doxorubicin, vincristine, prednisone (R-EPOCH), and 6 with R-CHOP with methotrexate, 3 g/m(2) . The overall response rate to front-line therapy was 85%. The 3-year progression free survival (PFS) and overall survival (OS) for all patients were 40 and 65%, respectively. The 3-year PFS for ABC- and GCB-subtypes was 34 and 45%, respectively. The 3-year OS for ABC- and GCB-subtypes was 62 and 67%, respectively. The median time to second treatment failure was 3 months and 1 month for ABC- and GCB-subtypes, respectively. Twenty of 28 (71%) transplanted patients with autologous, allogeneic, or both, relapsed. This study confirms the poor prognosis of de novo CD5+ DLBCL in a large multi-center cohort despite initial rituximab-containing chemotherapy and suggests that stem cell transplantation fails to salvage the majority of these patients. Approaches to prevent recurrence and/or novel therapies for relapsed disease are needed for this subgroup of DLBCL patients. PMID- 26800313 TI - "Periportal neoplasms"--a CT perspective: review article. AB - The periportal space is a potential space surrounding the portal vein and its intrahepatic branches. A variety of neoplasms can involve the periportal region, whether primary or secondary, owing to contiguous spread from surrounding hepatic parenchyma or from adjacent organs. CT plays an important role in not only diagnosing these lesions but also determining the extent of the disease. Most of the malignancies leading to the periportal spread manifest as periportal hypodensity either distinctly or in contiguity with the primary tumour. Even in known malignancies, periportal hypodensity commonly results from non-neoplastic causes like periportal oedema; hence, a knowledge of the imaging findings to ascertain its presence as well as to conclude the definite neoplastic spread is prudent. Periportal spread of neoplasm may suggest locally aggressive or disseminated disease (in extrahepatic malignancies), which may change management accordingly. PMID- 26800314 TI - Net-like superficial vascular malformation: clinical description and evidence for lymphatic origin. PMID- 26800316 TI - Health-Economics Analyses Applied to ELF Electric and Magnetic Fields. AB - Extremely low frequency electric and magnetic fields (ELF EMFs) are a common exposure for modern populations. The prevailing public-health protection paradigm is that quantitative exposure limits are based on the established acute effects, whereas the possible chronic effects are considered too uncertain for quantitative limits, but might justify precautionary measures. The choice of precautionary measures can be informed by a health-economics analysis (HEA). We consider four such analyses of precautionary measures that have been conducted at a national or state level in California, the Netherlands, the United Kingdom, and Israel. We describe the context of each analysis, examine how they deal with some of the more significant issues that arise, and present a comparison of the input parameters and assumptions used. The four HEAs are methodologically similar. The most significant qualitative choices that have to be made are what dose-response relationship to assume, what allowance if any to make for uncertainty, and, for a CBA only, what diseases to consider, and all four analyses made similar choices. These analyses suggest that, on the assumptions made, there are some low-cost measures, such as rephasing, that can be applied to transmission in some circumstances and that can be justifiable in cost-benefit terms, but that higher cost measures, such as undergrounding, become unjustifiable. Of the four HEAs, those in the United Kingdom and Israel were influential in determining the country's EMF policy. In California and Netherlands, the HEA may well have informed the debate, but the policy chosen did not stem directly from the HEA. PMID- 26800315 TI - Circulating memory B cells and plasmablasts are associated with the levels of serum immunoglobulin in patients with ulcerative colitis. AB - Humoural immunity is crucial for the pathogenesis of ulcerative colitis (UC), but the precise perturbation of B cell immunity is poorly understood. This study is aimed at evaluating the numbers of different subsets of circulating memory B cells, plasmablasts, and the levels of serum immunoglobulin in UC patients. Total of 23 patients with active UC and 14 healthy controls (HC) were examined for the numbers of different subsets of circulating memory B cells and plasmablasts before and after treatment with mesalazine for 8-12 weeks by flow cytometry. Disease activity was evaluated by the Mayo clinic score. The levels of serum immunoglobulin, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured in individual subjects. In comparison with that in HC, significantly reduced numbers of IgG(+) IgD(-) CD27(+) CD19(+) memory B cells, increased numbers of CD20(-) CD19(+) plasmablast subsets, and higher serum IgG levels were detected in UC patients. The concentrations of serum IgG, the numbers of CD138(+) CD38(+) CD20(-) CD19(+), and IgG(+) CD38(+) CD20(-) CD19(+) plasmablasts were negatively associated with the numbers of IgG(+) IgD(-) CD27(+) CD19(+) memory B cells. Furthermore, the values of Mayo clinic score, CRP, or ESR in UC patients were negatively correlated with the numbers of IgG(+) IgD(-) CD27(+) CD19(+) memory B cells, while positively correlated with the serum IgG levels and the numbers of plasmablast subsets. Following treatment with mesalazine, the numbers of circulating IgG(+) IgD(-) CD27(+) CD19(+) memory B cells were significantly increased, while the numbers of CD138(+) CD38(+) CD20(-) CD19(+) and IgG(+) CD38(+) CD20(-) CD19(+) plasmablasts were reduced in UC patients. These decreased IgG(+) IgD(-) CD27(+) CD19(+) memory B cells and increased plasmablasts may be involved in the pathogenic process of UC. PMID- 26800318 TI - Probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum) prevent NEC in VLBW infants fed breast milk but not formula. PMID- 26800319 TI - Motor imagery in spinal cord injured people is modulated by somatotopic coding, perspective taking, and post-lesional chronic pain. AB - Motor imagery (MI) allows one to mentally represent an action without necessarily performing it. Importantly, however, MI is profoundly influenced by the ability to actually execute actions, as demonstrated by the impairment of this ability as a consequence of lesions in motor cortices, limb amputations, movement limiting chronic pain, and spinal cord injury. Understanding MI and its deficits in patients with motor limitations is fundamentally important as development of some brain-computer interfaces and daily life strategies for coping with motor disorders are based on this ability. We explored MI in a large sample of patients with spinal cord injury (SCI) using a comprehensive battery of questionnaires to assess the ability to imagine actions from a first-person or a third-person perspective and also imagine the proprioceptive components of actions. Moreover, we correlated MI skills with personality measures and clinical variables such as the level and completeness of the lesion and the presence of chronic pain. We found that the MI deficits (1) concerned the body parts affected by deafferentation and deefferentation, (2) were present in first- but not in third person perspectives, and (3) were more altered in the presence of chronic pain. MI is thus closely related to bodily perceptions and representations. Every attempt to devise tools and trainings aimed at improving autonomy needs to consider the cognitive changes due to the body-brain disconnection. PMID- 26800323 TI - Annual Congress of the Chinese Blood Purification Center Administration Committee. August 20-22, 2015, Tianjin, China: Abstracts. PMID- 26800321 TI - Divergent impact of Toll-like receptor 2 deficiency on repair mechanisms in healthy muscle versus Duchenne muscular dystrophy. AB - Injury to skeletal muscle, whether acute or chronic, triggers macrophage-mediated innate immunity in a manner which can be either beneficial or harmful for subsequent repair. Endogenous ligands for Toll-like receptor 2 (TLR2) are released by damaged tissues and might play an important role in activating the innate immune system following muscle injury. To test this hypothesis, we compared macrophage behaviour and muscle repair mechanisms in mice lacking TLR2 under conditions of either acute (cardiotoxin-induced) or chronic (mdx mouse genetic model of Duchenne muscular dystrophy; DMD) muscle damage. In previously healthy muscle subjected to acute damage, TLR2 deficiency reduced macrophage numbers in the muscle post-injury but did not alter the expression pattern of the prototypical macrophage polarization markers iNOS and CD206. In addition, there was abnormal persistence of necrotic fibres and impaired regeneration in TLR2-/- muscles after acute injury. In contrast, TLR2 ablation in chronically diseased muscles of mdx mice not only resulted in significantly reduced macrophage numbers but additionally modified their phenotype by shifting from inflammatory (iNOS(pos) CD206(neg) ) to more anti-inflammatory (iNOS(neg) CD206(pos) ) characteristics. This decrease in macrophage-mediated inflammation was associated with ameliorated muscle histopathology and improved force-generating capacity of the dystrophic muscle. Our results suggest that the role of TLR2 in macrophage function and skeletal muscle repair depends greatly upon the muscle injury context, and raise the possibility that inhibition of TLR2 could serve as a useful therapeutic measure in DMD. PMID- 26800320 TI - Autotaxin Regulates Maintenance of Ovarian Cancer Stem Cells through Lysophosphatidic Acid-Mediated Autocrine Mechanism. AB - Ovarian cancer shows high mortality due to development of resistance to chemotherapy and relapse. Cancer stem cells (CSCs) have been suggested to be a major contributor in developing drug resistance and relapse in ovarian cancer. In this study, we isolated CSCs through sphere culture of A2780, SKOV3, OVCAR3 epithelial ovarian cancer cells and primary ovarian cancer cells from patients. We identified heat-stable factors secreted from ovarian CSCs stimulated migration and proliferation of CSCs. Mass spectrometry and ELISA analysis revealed that lysophosphatidic acid (LPA) was significantly elevated in CSC culture media compared with non-CSC culture media. Treatment of CSCs with LPA resulted in augmented CSC characteristics such as sphere-forming ability, resistance to anticancer drugs, tumorigenic potential in xenograft transplantation, and high expression of CSC-associated genes, including OCT4, SOX2, and aldehyde dehydrogenase 1. Treatment of CSCs with LPA receptor 1-specific inhibitors or silencing of LPA receptor 1 expression abrogated the LPA-stimulated CSC properties. Autotaxin, an LPA-producing enzyme, is highly secreted from ovarian CSCs, and pharmacological inhibition or knockdown of autotaxin markedly attenuated the LPA-producing, tumorigenic, and drug resistance potentials of CSCs. Clinicopathological analysis showed a significant survival disadvantage of patients with positive staining of autotaxin. In addition, we further identified that AKT1 activity was upregulated in ovarian CSCs through an LPA-dependent mechanism and silencing of AKT1 expression led to suppression of CSC characteristics. These results suggest that autotaxin-LPA-LPA receptor 1-AKT1 signaling axis is critical for maintaining CSC characteristics through an autocrine loop and provide a novel therapeutic target for ovarian CSCs. PMID- 26800326 TI - Precision Medicine. PMID- 26800324 TI - Phosphate starvation: a novel signal that triggers ESX-5 secretion in Mycobacterium tuberculosis. AB - Mycobacterium tuberculosis uses the Type VII ESX secretion systems to transport proteins across its complex cell wall. ESX-5 has been implicated in M. tuberculosis virulence, but the regulatory mechanisms controlling ESX-5 secretion were unknown. Here we uncover a link between ESX-5 and the Pst/SenX3-RegX3 system that controls gene expression in response to phosphate availability. The DNA binding response regulator RegX3 is normally activated by phosphate limitation. Deletion of pstA1, which encodes a Pst phosphate uptake system component, causes constitutive activation of RegX3. A DeltapstA1 mutant exhibited RegX3-dependent overexpression of esx-5 genes and hyper-secretion of the ESX-5 substrates EsxN and PPE41 when the bacteria were grown in phosphate-rich medium. In wild-type M. tuberculosis, phosphate limitation activated esx-5 transcription and secretion of both EsxN and PPE41, and this response required RegX3. Electrophoretic mobility shift assays revealed that RegX3 binds directly to a promoter within the esx-5 locus. Remarkably, phosphate limitation also induced secretion of EsxB, an effector of the virulence-associated ESX-1 secretion system, though this induction was RegX3 independent. Our work demonstrates that the Pst/SenX3-RegX3 system directly regulates ESX-5 secretion at the transcriptional level in response to phosphate availability and defines phosphate limitation as an environmental signal that activates ESX-5 secretion. PMID- 26800329 TI - Farewell to our Good Friend and Outstanding Colleague David Flockhart (1952 2015). PMID- 26800330 TI - Association between body mass index and outcome in Japanese ischemic stroke patients. AB - AIM: An association between body mass index (BMI) and stroke outcome have been reported, but the results are controversial. The aim of the present study was to evaluate whether BMI is associated with ischemic stroke outcome. METHODS: Consecutive Japanese acute ischemic stroke patients were analyzed. BMI was categorized as underweight (BMI <18.5 kg/m2 ), normal weight (18.5-24.9 kg/m2 ) and obese (>=25 kg/m2 ). BMI and short-term and long-term outcomes were examined. Short-term outcomes were evaluated using the modified Rankin scale score at hospitalization and discharge; modified Rankin scale >=3 was defined as a poor outcome. Long-term outcomes were evaluated by all-cause mortality. The recurrence rate was also evaluated in each BMI group. Values of P < 0.05 were considered significant. RESULTS: A total of 1206 acute ischemic stroke patients (760 men; mean age 72.5 years) were analyzed in the present study. There were 111 underweight cases (9.2%), 785 normal weight cases (65.1%) and 310 obese cases (25.7%). The underweight group had a significantly higher rate of poor short and long-term outcomes than the normal weight group. The outcomes of the obese group were not significantly different from those of the normal weight group. Recurrence was not significantly different among the groups. CONCLUSIONS: Lower BMI might be a predictor of poorer short-term and long-term stroke outcomes. Geriatr Gerontol Int 2017; 17: 369-374. PMID- 26800331 TI - A novel framework for analysing stakeholder interest in healthy foods: A case study on iodine biofortification. AB - Despite the availability of novel strategies to prevent micronutrient malnutrition, such as biofortification, limited understanding of stakeholders often hampers their success. We build upon the existing literature on protection motivations (PMT) and technology acceptance (TAM) to develop an integrated PMTAM model for analyzing stakeholders' reactions, on both the supply and demand sides. Regarding the latter, the case of the iodine biofortified food chain is used to evaluate African households' interest. All model constructs, and threat appraisal in particular, are decisive in determining the uptake of biofortification, while also social demographics and own nutrition status play an important role. PMID- 26800332 TI - A Stereoselective Synthesis of Lentiginosine. AB - A concise stereoselective synthesis of (-)-lentiginosine, an iminosugar endowed with an interesting proapoptotic activity, has been accomplished using an enantiopure pyrroline N-oxide building block derived from d-tartaric acid. Key steps are a totally diastereoselective nucleophilic addition to the cyclic nitrone followed by a combination of two simultaneous and two tandem reactions occurring under the same conditions in a single laboratory operation. Natural (+) lentiginosine can be synthesized by the same method but starting from l-tartaric acid. PMID- 26800333 TI - Tissue responses to fractional transient heating with sinusoidal heat flux condition on skin surface. AB - A fractional model of Bioheat equation for describing quantitatively the thermal responses of skin tissue under sinusoidal heat flux conditions on skin surface is given. Laplace transform technique is used to obtain the solution in a closed form. The resulting formulation is applied to one-dimensional application to investigate the temperature distribution in skin with instantaneous surface heating for different cases. According to the numerical results and its graphs, conclusion about the fractional bioheat transfer equation has been constructed. Sensitivity analysis is performed to explore the thermal effects of various control parameters on tissue temperature. The comparisons are made with the results obtained in the case of the absence of time-fractional order. (c) 2016 Japanese Society of Animal Science. PMID- 26800334 TI - Prototype-based models in machine learning. AB - An overview is given of prototype-based models in machine learning. In this framework, observations, i.e., data, are stored in terms of typical representatives. Together with a suitable measure of similarity, the systems can be employed in the context of unsupervised and supervised analysis of potentially high-dimensional, complex datasets. We discuss basic schemes of competitive vector quantization as well as the so-called neural gas approach and Kohonen's topology-preserving self-organizing map. Supervised learning in prototype systems is exemplified in terms of learning vector quantization. Most frequently, the familiar Euclidean distance serves as a dissimilarity measure. We present extensions of the framework to nonstandard measures and give an introduction to the use of adaptive distances in relevance learning. PMID- 26800335 TI - Ion chromatography for the separation of heparin and structurally related glycoaminoglycans: A review. AB - The global crisis resulting from adulterated heparin in late 2007 and early 2008 revived the importance of analytical techniques for the purity analysis of heparin products. The utilization of ion chromatography techniques for the separation, detection, and structural determination of heparin and structurally related glycoaminoglycans, including their corresponding oligosaccharides, has become increasingly important. This review summarizes the primary HPLC approaches, particularly strong anion exchange, weak ion exchange, and reversed phase ion-pair, used for heparin purity analysis as well as structural characterization. Strong anion exchange HPLC has been studied most extensively and currently offers the best separation of crude heparin and heparin-like compounds. Weak anion exchange HPLC has been shown to provide shorter analysis times with lower salt concentrations in the mobile phase but is not as widely developed for the separation of all glycoaminoglycans of interest. Reversed-phase ion-pair HPLC offers fast and effective separations of oligosaccharides derived from glycoaminoglycans that can be coupled to mass spectrometry for structural analysis. However, this method generally does not provide sufficient retention of intact glycoaminoglycans. PMID- 26800336 TI - Establishment of polyethylene-glycol-mediated protoplast transformation for Lecanicillium lecanii and development of virulence-enhanced strains against Aphis gossypii. AB - BACKGROUND: Lecanicillium lecanii has been developed as a biopesticide and used in biological control of several agricultural insects. To improve fungal virulence, an optimised polyethylene glycol (PEG)-mediated protoplast transformation system was established for L. lecanii. Pr1A-like cuticle-degrading protease gene (Cdep1) from Beauveria bassiana was transferred into L. lecanii, and its resulting activity against Aphis gossypii was assessed. RESULTS: The optimised protoplast generation yielded 2.5 * 10(8) protoplasts g(-1) wet mycelium of fungi, and gave nearly 98% viability and 80% regeneration on plates. Protease activities were increased about fivefold in transformants expressing CDEP1. The median lethal concentration (LC50 ) for transformants expressing CDEP1 was twofold lower than that for the wild type (WT). The median survival time (LT50 ) for transformants expressing CDEP1 was also 14.2% shorter than that for WT, though no significant difference. There were no significant differences in conidial germination as colony growth and conidial yield on plates between transformants expressing CDEP1 and WT. The transformants expressing CDEP1 grew significantly quicker than WT in insects. The transformants expressing CDEP1 were lower in conidial yields on insect cadavers, but insignificantly different from WT. CONCLUSION: The PEG-mediated protoplast transformation system was effective for L. lecanii, and the expression of CDEP1 significantly enhanced fungal virulence against cotton aphids. (c) 2016 Society of Chemical Industry. PMID- 26800337 TI - A position statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology: What about racial differences? PMID- 26800338 TI - MiR-382 inhibits cell growth and invasion by targeting NR2F2 in colorectal cancer. AB - Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. MiR-382 has been found to have a decreased expression and the ability to suppress tumorigenesis in certain cancers. However, the role of miR-382 in CRC has not been sufficiently investigated. NR2F2 (also known as COUP-TFII), a member of the steroid/thyroid receptor superfamily, is often aberrantly activated in various tumors, but it is currently unclear whether NR2F2 may be a target of miR-382. In the present study, we investigated the role of miR-382 in CRC and identified the regulation of NR2F2 by miR-382. We observed that miR-382 was aberrantly downregulated in CRC. Transfection with miR-382 mimics impeded the growth, migration, and invasion of CRC cells. The direct binding of miR-382 to the 3' untranslated region (3' UTR) of NR2F2 was confirmed using a luciferase reporter gene assay. We showed that the relative expression levels of NR2F2 were significantly higher in CRC tissues compared with normal adjacent mucosa. A Kaplan-Meier analysis indicated that patients with high NR2F2 expression had a poor overall survival. Knockdown of NR2F2 inhibited CRC cell growth, migration, and invasion. Ectopic expression of NR2F2 mitigated miR-382 suppression of CRC cell proliferation, migration, and invasion. In conclusion, the present study describes a potential mechanism underlying a miR-382/NR2F2 link contributing to CRC development. Our results demonstrate that miR-382 represents a potential strategy against CRC. (c) 2016 Wiley Periodicals, Inc. PMID- 26800340 TI - Micellization Behavior of Surface Active Ionic Liquids Having Aromatic Counterions in Aqueous Media. AB - Amphiphilic ionic liquids (ILs) based on 3-hexadecyl-1-methyl imidazolium cation, [C16mim](+), having aromatic anions, 4-hydroxybenzenesulfonate, [HBS], benzenesulfonate, [BS], and p-toluenesulfonate, [PTS], as counterions have been synthesized and investigated for their micellization behavior in aqueous medium. The surface activity of investigated ILs has been established by surface tension measurements, whereas bulk behavior has been investigated by conductivity and steady-state fluorescence measurements. The investigated ILs exhibited 2-3 fold lower critical micelle concentration (cmc) as compared to analogous ILs or conventional surfactants with nonaromatic counterions. The polarity of the cybotactic region of pyrene decreases along with decrease in extent of water penetration toward palisade layer of micelle with increase in hydrophobicity of counterion. Relatively more hydrophobic anions, i.e., [BS](-) and [PTS](-), have been found to form excimer in palisade layer of micelle, whereas [HBS](-) remains in close vicinity of imidazolium head groups of micelle as established from inherent fluorescence of aromatic anions. Isothermal titration calorimetry measurements have provided insights into thermodynamics of micelles. The strength of binding and relative position of aromatic anions in micelle has been found to affect the characteristic properties of micelle as deduced from (1)H NMR measurements. The micelles with different sizes and shapes such as spherical, partially elongated, or long rod-like micelles have been observed for different ILs depending of nature of aromatic anions as established from dynamic light scattering and transmission electron microscopy measurements. PMID- 26800339 TI - Involvement of luxS in Biofilm Formation by Capnocytophaga ochracea. AB - Capnocytophaga ochracea is present in the dental plaque biofilm of patients with periodontitis. Biofilm cells change their phenotype through quorum sensing in response to fluctuations in cell-population density. Quorum sensing is mediated by auto-inducers (AIs). AI-2 is involved in intercellular signaling, and production of its distant precursor is catalyzed by LuxS, an enzyme involved in the activated methyl cycle. Our aim was to clarify the role of LuxS in biofilm formation by C. ochracea. Two luxS-deficient mutants, TmAI2 and LKT7, were constructed from C. ochracea ATCC 27872 by homologous recombination. The mutants produced significantly less AI-2 than the wild type. The growth rates of these mutants were similar to that of the wild-type in both undiluted Tryptic soy broth and 0.5 * Tryptic soy broth. However, according to crystal violet staining, they produced significantly less biofilm than the wild type. Confocal laser scanning microscopy and scanning electron microscopy showed that the biofilm of the TmAI2 strain had a rougher structure than that of the wild type. Complementation of TmAI-2 with extrinsic AI-2 from the culture supernatant of wild-type strain did not restore biofilm formation by the TmAI2 strain, but complementation of LKT7 strain with luxS partially restored biofilm formation. These results indicate that LuxS is involved in biofilm formation by C. ochracea, and that the attenuation of biofilm formation by the mutants is likely caused by a defect in the activated methyl cycle rather than by a loss of AI-2. PMID- 26800341 TI - Bacterial Effector Nanoparticles as Breast Cancer Therapeutics. AB - Bacterial pathogens trigger cell death by a variety of mechanisms, including injection of effector proteins. Effector proteins have great potential as anticancer agents because they efficiently subvert a variety of eukaryotic signaling pathways involved in cancer development, drug resistance, and metastasis. In breast cancer, MAPK and NFkappaB pathways are known to be dysregulated. YopJ, an effector from Yersinia pestis, downregulates MAPK and NFkappaB pathways to induce cell death in specific cell types. We expressed YopJ in Escherichia coli as a fusion protein with glutathione S-transferase (GST), forming self-assembled protein nanoparticles with diameters of 100 nm. YopJ-GST nanoparticles efficiently delivered protein to cells, replacing the need for the pathogen secretion mechanism for effector delivery to cells. These nanoparticles induced dose and time dependent death in SKBR-3 breast cancer cells. After 72 h, 97% of cells died, significantly more than with the same molar dose of doxorubicin. Treatment with sublethal doses of nanoparticles decreased cell migration in vitro and downregulated the MAPK ERK 1/2 pathway, which has been correlated to metastasis. Exposure to a panel of breast cancer cell lines showed that YopJ-GST nanoparticles are cytotoxic to different subtypes, including doxorubicin resistant cells. However, they were not cytotoxic to NIH/3T3 fibroblasts or HeLa cells. Thus, YopJ-GST nanoparticles demonstrate the potential of effector proteins as breast cancer therapeutics with selective cytotoxicity and the capacity to decrease metastatic predictive behaviors. PMID- 26800344 TI - Development of a Cultural Awareness Scale for Occupational Therapy Students in Latin America: A Qualitative Delphi Study. AB - Cultural awareness is a key issue in healthcare worldwide. Valid and reliable assessments are needed to assess cultural awareness for occupational therapy students. The purpose of this study was to develop a scale to assess cultural awareness for Latin American occupational therapy students. A Delphi design was implemented considering four rounds with experts from four countries. A 30-item scale in Spanish was developed to assess three categories of items: personal, therapeutic strategies and persons' cultures. The experts highlighted local features for professional practice as a key aspect of the scale. Local differences in practice were considered with the profession's traditions and prevailing knowledge across the scale. A participatory strategy and an international group of experts enriched the cultural relevance. A subsequent study of statistical reliability is required (the scale is not presented in an extended version here). Further research should consider the application of the scale and strategies to improve cultural awareness across the curricula. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26800342 TI - Developmental Patterning as a Quantitative Trait: Genetic Modulation of the Hoxb6 Mutant Skeletal Phenotype. AB - The process of patterning along the anterior-posterior axis in vertebrates is highly conserved. The function of Hox genes in the axis patterning process is particularly well documented for bone development in the vertebral column and the limbs. We here show that Hoxb6, in skeletal elements at the cervico-thoracic junction, controls multiple independent aspects of skeletal pattern, implicating discrete developmental pathways as substrates for this transcription factor. In addition, we demonstrate that Hoxb6 function is subject to modulation by genetic factors. These results establish Hox-controlled skeletal pattern as a quantitative trait modulated by gene-gene interactions, and provide evidence that distinct modifiers influence the function of conserved developmental genes in fundamental patterning processes. PMID- 26800345 TI - Comparison of the Belgian Rheumatoid Arthritis Disability Assessment and Health Assessment Questionnaires as Tools to Predict the Need for Support Measures in Patients with Rheumatoid Arthritis. AB - OBJECTIVE: Scores on the Health Assessment Questionnaire (HAQ) predict the need for support measures in patients with rheumatoid arthritis (RA). In this study we compare the performance of the HAQ in this context with that of the more disease specific Belgian Rheumatoid Arthritis Disability Assessment (BRADA) questionnaire. METHODS: In this multicenter observational study, patients with RA and disease duration of at least one year who consulted their rheumatologist for a routine follow-up visit filled out the HAQ, and BRADA questionnaires. The performance of HAQ and BRADA to predict the need for support measures available to patients with RA was evaluated using Receiver Operator Characteristic (ROC) curves, with the expert opinion of the rheumatologist as a reference. RESULTS: The study analyzed data of 301 patients with RA (70.8% females) with mean age 59.8 +/- 12.8, disease duration 11.4 +/- 9.3 years, and DAS28 values of 2.84 +/- 1.18. HAQ scores averaged 0.97 +/- 0.73 and BRADA scores were 3.92 +/- 3.49 over the last week and 3.89 +/- 3.50 over the last 3 months. The area under the ROC curves for the BRADA scores for the support measures investigated ranged from 0.702 to 0.862 and did not differ significantly from those of the HAQ (range 0.725-0.860). CONCLUSION: The disease-specific BRADA questionnaire is equivalent to the HAQ in predicting the need for support measures in patients with stable RA. PMID- 26800349 TI - C-C Bond-Forming Strategy by Manganese-Catalyzed Oxidative Ring-Opening Cyanation and Ethynylation of Cyclobutanol Derivatives. AB - A novel C-C bond-forming strategy employing manganese-catalyzed ring-opening of cyclobutanol substrates, followed by cyanation or ethynylation, is described. A cyano C1 unit and ethynyl C2 unit are regiospecifically introduced to the gamma position of ketones at room temperature, providing a mild yet powerful method for production of elusive aliphatic nitriles and alkynes. All transformations described are based on a common sequence: 1) oxidative ring-opening of cyclobutanol substrates by C-C bond cleavage; 2) radical addition to triple bonds bearing an arylsulfonyl group; and 3) radical-mediated C-S bond cleavage. PMID- 26800347 TI - Ambulatory movements, team dynamics and interactions during robot-assisted surgery. AB - OBJECTIVE: To analyse ambulatory movements and team dynamics during robot assisted surgery (RAS), and to investigate whether congestion of the physical space associated with robotic technology led to workflow challenges or predisposed to errors and adverse events. METHODS: With institutional review board approval, we retrospectively reviewed 10 recorded robot-assisted radical prostatectomies in a single operating room (OR). The OR was divided into eight zones, and all movements were tracked and described in terms of start and end zones, duration, personnel and purpose. Movements were further classified into avoidable (can be eliminated/improved) and unavoidable (necessary for completion of the procedure). RESULTS: The mean operating time was 166 min, of which ambulation constituted 27 min (16%). A total of 2 896 ambulatory movements were identified (mean: 290 ambulatory movements/procedure). Most of the movements were procedure-related (31%), and were performed by the circulating nurse. We identified 11 main pathways in the OR; the heaviest traffic was between the circulating nurse zone, transit zone and supply-1 zone. A total of 50% of ambulatory movements were found to be avoidable. CONCLUSION: More than half of the movements during RAS can be eliminated with an improved OR setting. More studies are needed to design an evidence-based OR layout that enhances access, workflow and patient safety. PMID- 26800350 TI - Metanephric adenoma: Cytological, histological, and molecular diagnosis of a case. PMID- 26800352 TI - Heroin Use and Injection Risk Behaviors in Colombia: Implications for HIV/AIDS Prevention. AB - BACKGROUND: Heroin production in Colombia has increased dramatically in recent decades, and some studies point to an increase in local heroin use since the mid 1990s. Despite this rapid increase, little is known about the effects of these activities on heroin injection within Colombia. One of the biggest concerns surrounding heroin injection is the potential spread of HIV through drug user networks. OBJECTIVES: This article examines injection risk behaviors among heroin injectors in the Colombian cities of Medellin and Pereira to explore the implications for possible increased HIV transmission within this group. METHODS: A cross-sectional study used respondent-driving sampling to recruit a sample of 540 people who inject drugs (PWID) over 18 years of age (Medellin: n = 242, Pereira: n = 298). Structured interviews with each participant were conducted using the World Health Organization Drug Injection Study Phase II Survey. An HIV test was also administered. RESULTS: Information regarding the socio demographics, injection drug use, HIV risk and transmission behaviors, injection risk management, and HIV knowledge and prevalence of participants are reported. The study identified many young, newly initiated injectors who engage in risky injection practices. The study also found that HIV prevalence is fairly low among participants (2.7%). CONCLUSIONS/IMPORTANCE: Findings indicate a potential risk for the spread of HIV among PWID in Colombia given their widespread sharing practices, high rate of new injector initiation, and unsafe syringe cleaning practices. Colombia has a possibly time-limited opportunity to prevent an HIV epidemic by implementing harm reduction interventions among young, newly initiated PWID. PMID- 26800353 TI - Studies on the Simultaneous Formation of Aroma-Active and Toxicologically Relevant Vinyl Aromatics from Free Phenolic Acids during Wheat Beer Brewing. AB - During the brewing process of wheat beer, the desired aroma-active vinyl aromatics 2-methoxy-4-vinylphenol and 4-vinylphenol as well as the undesired and toxicologically relevant styrene are formed from their respective precursors, free ferulic acid, p-coumaric acid, and cinnamic acid, deriving from the malts. Analysis of eight commercial wheat beers revealed high concentrations of 2 methoxy-4-vinylphenol and 4-vinylphenol always in parallel with high concentrations of styrene or low concentrations of the odorants in parallel with low styrene concentrations, suggesting a similar pathway. To better understand the formation of these vinyl aromatics, each process step of wheat beer brewing and the use of different strains of Saccharomyces cerevisiae were evaluated. During wort boiling, only a moderate decarboxylation of free phenolic acids and formation of desired and undesired vinyl aromatics were monitored due to the thermal treatment. In contrast, this reaction mainly occurred enzymatically catalyzed during fermentation with S. cerevisiae strain W68 with normal Pof(+) activity (phenolic off-flavor) resulting in a wheat beer eliciting the typical aroma requested by consumers due to high concentrations of 2-methoxy-4 vinylphenol (1790 MUg/L) and 4-vinylphenol (937 MUg/L). Unfortunately, also a high concentration of undesired styrene (28.3 MUg/L) was observed. Using a special S. cerevisiae strain without Pof(+) activity resulted in a significant styrene reduction (G Is Associated with Gallstone Disease in Chinese Patients. AB - Niemann Pick Type C1 Like 1 (NPC1L1) protein plays a key role in intestinal and hepatic cholesterol metabolism in humans. Genetic variation in NPC1L1 has been widely studied in recent years. We analyzed NPC1L1 single nucleotide polymorphisms in Chinese gallstone disease patients to investigate their association with gallstone disease. NPC1L1 mRNA expression was also measured in liver biopsies from patients with cholesterol gallstone disease and compared between genotypes. The G allele of the g1679C>G (rs2072183) polymorphism was significantly more prevalent in patients with gallstones compared with gallstone free subjects. Moreover, patients carrying the G allele had lower hepatic NPC1L1 mRNA expression and higher biliary cholesterol (molar percentages) and cholesterol saturation index. Our study suggests that the G allele of the NPC1L1 polymorphism g1679C>G may be a positive marker of gallstone formation risk. PMID- 26800365 TI - Developing drugs for use before, during and soon after percutaneous coronary intervention. AB - INTRODUCTION: Percutaneous coronary intervention (PCI) is a milestone for treating coronary artery disease (CAD). Antithrombotic therapy is essential to prevent ischemic complications, including the microvascular no-reflow, while minimizing bleeding events. AREAS COVERED: This overview discusses available and developing drugs for PCI including anticoagulants, antiplatelets and treatment of no-reflow. EXPERT OPINION: For years unfractionated heparin (UFH) has been the unique anticoagulant to be used before and during PCI. Enoxaparin showed similar efficacy and safety, yet, based on recent trials, bivalirudin has been shown to have some benefits, particularly for patients with ST-segment elevation myocardial infarction (STEMI). The evidence concerning new anticoagulants is still preliminary, except for new oral anticoagulants, particularly rivaroxaban that showed intriguing findings and is currently under investigation. Dual antiplatelet therapy (DAPT) is the standard of care after PCI, but new developments have recently emerged. Indeed, ticagrelor and prasugrel are currently recommended over clopidogrel due to their significant reduction of ischemic events in acute coronary syndrome (ACS) whereas clopidogrel remains the choice in stable CAD. Among new agents, vorapaxar and cangrelor showed positive but limited evidence and might be considered at least in selected patients. Conversely, evidence on effective treatments for no-reflow remains limited and would require future dedicated research. PMID- 26800366 TI - Influence of Topical, Systemic and Combined Application of Antioxidants on the Barrier Properties of the Human Skin. AB - BACKGROUND: The formation of free radicals in human skin by solar ultraviolet radiation is considered to be the main reason for extrinsic skin aging. The antioxidants in human tissue represent an efficient protection system against the destructive action of these reactive free radicals. In this study, the parameters of the skin, epidermal thickness, stratum corneum moisture, elasticity and wrinkle volume, were determined before and after the treatment with antioxidant- or placebo-containing tablets and creams. METHODS: The study included 5 groups of 15 volunteers each, who were treated for 2 months with antioxidant-containing or placebo tablets, creams or a combination of antioxidant-containing tablets and cream. The skin parameters were measured at time point 0 and at week 8 utilizing ultrasound for the determination of epidermal thickness, a corneometer for stratum corneum moisture measurements, skin profilometry for quantifying the wrinkle volume and a cutometer for determining the elasticity. RESULTS: The verum cream had a positive influence on epidermal thickness, elasticity and skin moisture, but the verum tablets improved the epidermal thickness only. The combined application of verum tablets and creams led to a significant improvement of all investigated skin parameters, whereas the application of placebo tablets or cream did not influence any parameters. CONCLUSION: The topical and oral supplementation of antioxidants can be an instrument to improve several skin parameters and potentially counteract or decelerate the process of extrinsic skin aging. PMID- 26800368 TI - Driving forces for the pressure-induced aggregation of poly(N isopropylacrylamide) in water. AB - Driving forces for the pressure-induced aggregation of poly(N isopropylacrylamide) (PNiPA) in water are investigated by performing extensive molecular dynamics simulations. First, we observe that the model short oligomer of PNiPA with a modified OPLS-AA force field in water shrinks with increasing pressure. At varying pressures, the potentials of mean force (PMFs) between a pair of N-isopropylpropionamide (NiPPA) molecules, the repeating unit of PNiPA, are obtained and decomposed into the nonpolar and Coulombic contributions. The nonpolar contribution is the PMF between the hypothetical nonpolar NiPPA molecules in the solvent, which is mainly due to the molecular volume effect. The attractive force between NiPPA molecules is enhanced at higher pressures in agreement with the behavior of PNiPA. This pressure dependence of the PMF is caused by the growing nonpolar contribution at higher pressures. In contrast, the Coulombic contribution to the PMF becomes higher overall, making the mean force less attractive or more repulsive, with increasing pressure. The strength of the aggregation and its pressure dependence of the nonpolar contribution in water are closely reproduced even in nonpolar solvents. The degree of the pressure dependence is explained by the isothermal compressibility or the tightness of the solvation shell around an isolated solute, without regard to the existence and variation of hydrogen bond networks in a solvent. The role of hydrogen bonds in the aggregation of NiPPA and PNiPA molecules is also discussed. PMID- 26800367 TI - Longitudinal change in magnetic susceptibility of new enhanced multiple sclerosis (MS) lesions measured on serial quantitative susceptibility mapping (QSM). AB - PURPOSE: To measure the longitudinal change in multiple sclerosis (MS) lesion susceptibility using quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: The study was approved by our Institutional Review Board. Longitudinal changes in quantitative susceptibility values of new enhanced-with-Gd MS lesions were measured at baseline magnetic resonance imaging (MRI) and on a follow-up MRI in 29 patients within 2 years using a 3D multiple echo gradient echo sequence on a 3T scanner. Paired t-test and the generalized estimating equations (GEE) model was used to analyze the longitudinal change. RESULTS: Lesion susceptibility values relative to normal-appearing white matter (NAWM) changed from 3.61 +/- 6.11 ppb when enhanced-with-Gd at the baseline MRI to 20.42 +/- 10.23 ppb when not-enhanced-with-Gd at the follow-up MRI (P < 0.001). CONCLUSION: MS lesion susceptibility value increases significantly as the lesion evolves from enhanced with-Gd to not-enhanced-with-Gd, serving as a disease biomarker. J. Magn. Reson. Imaging 2016;44:426-432. PMID- 26800369 TI - Novel alpha-L-Fucosidases from a Soil Metagenome for Production of Fucosylated Human Milk Oligosaccharides. AB - This paper describes the discovery of novel alpha-L-fucosidases and evaluation of their potential to catalyse the transglycosylation reaction leading to production of fucosylated human milk oligosaccharides. Seven novel alpha-L-fucosidase encoding genes were identified by functional screening of a soil-derived metagenome library and expressed in E. coli as recombinant 6xHis-tagged proteins. All seven fucosidases belong to glycosyl hydrolase family 29 (GH 29). Six of the seven alpha-L-fucosidases were substrate-inhibited, moderately thermostable and most hydrolytically active in the pH range 6-7, when tested with para-nitrophenyl alpha-L-fucopyranoside (pNP-Fuc) as the substrate. In contrast, one fucosidase (Mfuc6) exhibited a high pH optimum and an unusual sigmoidal kinetics towards pNP Fuc substrate. When tested for trans-fucosylation activity using pNP-Fuc as donor, most of the enzymes were able to transfer fucose to pNP-Fuc (self condensation) or to lactose. With the alpha-L-fucosidase from Thermotoga maritima and the metagenome-derived Mfuc5, different fucosyllactose variants including the principal fucosylated HMO 2'-fucosyllactose were synthesised in yields of up to ~6.4%. Mfuc5 was able to release fucose from xyloglucan and could also use it as a fucosyl-donor for synthesis of fucosyllactose. This is the first study describing the use of glycosyl hydrolases for the synthesis of genuine fucosylated human milk oligosaccharides. PMID- 26800371 TI - Improved oral efficacy of epirubicin through polymeric nanoparticles: pharmacodynamic and toxicological investigations. AB - Epirubicin (EPI) elicits poor-oral bioavailability hence commercially available as injection for intravenous administration which follows a rapid increase and fast decay in plasma drug concentration often needs a frequent dosing that may lead to serious side effects. Aim of the present study is to develop a nanoparticulate system which could deliver epirubicin effectively via oral administration and could eventually promote new concept "chemotherapy at home." In this perspective, epirubicin loaded Poly-lactide-co-glycolic acid nanoparticles (EPI-NPs) were developed by double emulsion evaporation techniques and evaluated for its safety and efficacy against Ehrlich's Ascites (EAT) induced tumor in balb/c mice. In vivo fate of nanoparticles after oral administration in Albino wistar rats was also studied. EPI-NPs showed marked reduction in tumor size ~40% while tumor size was increased 3.55 and 3.28 folds in control as well as in group treated orally with free epirubicin solution (EPI-S), respectively. Furthermore, toxicological evaluation demonstrated insignificant difference in levels of biomarkers including MDA, CAT, SOD, LDH, CK-MB, AST and ALT when EPI NPs-oral treatment was compared with control group while levels of these biomarkers were found extremely significant in group treated with EPI-S (i.v). and demonstrated increment in LDH (p < 0.001), CK-MB (p < 0.001), AST (p < 0.001), ALT (p < 0.001) and MDA levels (p < 0.001) and reduction in SOD (p < 0.001) and CAT levels (p < 0.001) thus confirmed better safety profile of EPI-NPs oral than EPI-S i.v. Biodistribution study demonstrated the presence of NPs in different body organs and blood which suggests probability of NPs translocation across intestine thus at the tumor site. PMID- 26800375 TI - A Message to the Readers of Neuropediatrics. PMID- 26800376 TI - Involvement of autophagy in the procedure of endoplasmic reticulum stress introduced apoptosis in bone marrow mesenchymal stem cells from nonobese diabetic mice. AB - Recent studies showed that bone marrow mesenchymal stem cells (BM-MSCs) from nonobese diabetic (NOD) mice exhibited the phenomenon of apoptosis. However, the mechanisms of apoptosis remained largely unknown. In this study, endoplasmic reticulum (ER) stress and autophagy were evidenced in BM-MSCs from NOD mice for the first time. We found the ER stress-mediated apoptosis was supported by the up regulation of ER stress markers including augmented phosphorylation of phosphorylated protein kinase RNA-like ER kinase and eukaryotic translation initiator factor 2alpha as well as cleavage of caspase-3. Evidence of autophagy included the formation of the acidic vesicular organelles and increase of LC3 accumulation. Intriguingly, blockage of ER stress could reduce the apoptosis of BM-MSCs from NOD mice and alleviated accumulation of LC3, which indicated that ER stress induced apoptosis and autophagy. Furthermore, our results showed that the mechanism of ER stress-induced autophagy was associated with the decrease of p-S6 (a marker of mTOR activity). Here, we demonstrated that ER stress-induced cell death was mediated by autophagy that was partly attributed to the inactivation of the mammalian target of rapamycin. SIGNIFICANCE PARAGRAPH: We report for the first time that endoplasmic reticulum (ER) stress mediated apoptosis of bone marrow mesenchymal stem cells (BM-MSCs) from nonobese diabetic (NOD) mice. The evidence of autophagy was also found in BM-MSCs from NOD mice, included the formation of the acidic vesicular organelles and increase of LC3 accumulation. Furthermore, we demonstrated that ER stress-induced cell death was mediated by autophagy that was partly attributed to the inactivation of the mammalian target of rapamycin. Deciphering the mechanisms of ER stress signalling involved in the apoptosis of BM-MSCs from NOD mice will help improve transplantation efficacy of BM-MSCs in type 1 diabetes patients. PMID- 26800372 TI - Amyloid Plaque-Associated Oxidative Degradation of Uniformly Radiolabeled Arachidonic Acid. AB - Oxidative stress is a frequently observed feature of Alzheimer's disease, but its pathological significance is not understood. To explore the relationship between oxidative stress and amyloid plaques, uniformly radiolabeled arachidonate was introduced into transgenic mouse models of Alzheimer's disease via intracerebroventricular injection. Uniform labeling with carbon-14 is used here for the first time, and made possible meaningful quantification of arachidonate oxidative degradation products. The injected arachidonate entered a fatty acid pool that was subject to oxidative degradation in both transgenic and wild-type animals. However, the extent of its degradation was markedly greater in the hippocampus of transgenic animals where amyloid plaques were abundant. In human Alzheimer's brain, plaque-associated proteins were post-translationally modified by hydroxynonenal, a well-known oxidative degradation product of arachidonate. These results suggest that several recurring themes in Alzheimer's pathogenesis, amyloid beta proteins, transition metal ions, oxidative stress, and apolipoprotein isoforms, may be involved in a common mechanism that has the potential to explain both neuronal loss and fibril formation in this disease. PMID- 26800377 TI - CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Israeli experience. AB - PURPOSE: To describe the experience of five Israeli pediatric epilepsy clinics treating children and adolescents diagnosed as having intractable epilepsy with a regimen of medical cannabis oil. METHODS: A retrospective study describing the effect of cannabidiol (CBD)-enriched medical cannabis on children with epilepsy. The cohort included 74 patients (age range 1-18 years) with intractable epilepsy resistant to >7 antiepileptic drugs. Forty-nine (66%) also failed a ketogenic diet, vagal nerve stimulator implantation, or both. They all started medical cannabis oil treatment between 2-11/2014 and were treated for at least 3 months (average 6 months). The selected formula contained CBD and tetrahydrocannabinol at a ratio of 20:1 dissolved in olive oil. The CBD dose ranged from 1 to 20mg/kg/d. Seizure frequency was assessed by parental report during clinical visits. RESULTS: CBD treatment yielded a significant positive effect on seizure load. Most of the children (66/74, 89%) reported reduction in seizure frequency: 13 (18%) reported 75-100% reduction, 25 (34%) reported 50-75% reduction, 9 (12%) reported 25-50% reduction, and 19 (26%) reported <25% reduction. Five (7%) patients reported aggravation of seizures which led to CBD withdrawal. In addition, we observed improvement in behavior and alertness, language, communication, motor skills and sleep. Adverse reactions included somnolence, fatigue, gastrointestinal disturbances and irritability leading to withdrawal of cannabis use in 5 patients. CONCLUSIONS: The results of this multicenter study on CBD treatment for intractable epilepsy in a population of children and adolescents are highly promising. Further prospective, well-designed clinical trials using enriched CBD medical cannabis are warranted. PMID- 26800378 TI - Hybrubins: Bipyrrole Tetramic Acids Obtained by Crosstalk between a Truncated Undecylprodigiosin Pathway and Heterologous Tetramic Acid Biosynthetic Genes. AB - Heterologous expression of bacterial artificial chromosome (BAC) clones from the genomic library of Streptomyces variabilis Snt24 in Streptomyces lividans SBT5 which carried a truncated undecylprodigiosin biosynthetic gene cluster led to the identification of hybrubins A-C. The hybrubins represent a new carbon skeleton in which a tetramic acid moiety is fused to a 2,2'-dipyrrole building block. Gene knockout experiments confirmed that hybrubins are derived from two convergent biosynthetic pathways including the remaining genomic red genes of S. lividans SBT5 as well as the BAC encoded hbn genes for the production of 5 ethylidenetetramic acid. A possible biosynthetic pathway was also proposed. PMID- 26800380 TI - Maternal arterial elasticity in the first trimester as a predictor of birthweight. AB - The early detection of foetal growth restriction and macrosomia is an important goal of modern obstetric care. Aberrant foetal growth is an important cause of perinatal morbidity and mortality. Current modalities for detecting the abnormal foetal growth are often inadequate. Pulse wave analysis using applanation tonometry is a simple and non-invasive test that provides information about the cardiovascular system. Arterial elasticity has previously been implicated in the pathophysiology of pre-eclampsia and cardiovascular disease. Our study examined the relationship between maternal arterial elasticity and birthweight by using pulse wave analysis. We discovered that increased large artery elasticity predicted a larger baby at birth. Large artery elasticity therefore has the potential to act as a useful screening tool which may help in the prediction of women who are at risk of aberrant foetal growth. PMID- 26800383 TI - Optimal control design of turbo spin-echo sequences with applications to parallel transmit systems. AB - PURPOSE: The design of turbo spin-echo sequences is modeled as a dynamic optimization problem which includes the case of inhomogeneous transmit radiofrequency fields. This problem is efficiently solved by optimal control techniques making it possible to design patient-specific sequences online. THEORY AND METHODS: The extended phase graph formalism is employed to model the signal evolution. The design problem is cast as an optimal control problem and an efficient numerical procedure for its solution is given. The numerical and experimental tests address standard multiecho sequences and pTx configurations. RESULTS: Standard, analytically derived flip angle trains are recovered by the numerical optimal control approach. New sequences are designed where constraints on radiofrequency total and peak power are included. In the case of parallel transmit application, the method is able to calculate the optimal echo train for two-dimensional and three-dimensional turbo spin echo sequences in the order of 10 s with a single central processing unit (CPU) implementation. The image contrast is maintained through the whole field of view despite inhomogeneities of the radiofrequency fields. CONCLUSION: The optimal control design sheds new light on the sequence design process and makes it possible to design sequences in an online, patient-specific fashion. Magn Reson Med 77:361-373, 2017. (c) 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. PMID- 26800384 TI - A Synthetic Glycopeptide Vaccine for the Induction of a Monoclonal Antibody that Differentiates between Normal and Tumor Mammary Cells and Enables the Diagnosis of Human Pancreatic Cancer. AB - In studies within the realm of cancer immunotherapy, the synthesis of exactly specified tumor-associated glycopeptide antigens is shown to be a key strategy for obtaining a highly selective biological reagent, that is, a monoclonal antibody that completely differentiates between tumor and normal epithelial cells and specifically marks the tumor cells in pancreas tumors. Mucin MUC1, which is overexpressed in many prevalent cancers, was identified as a promising target for this strategy. Tumor-associated MUC1 differs significantly from that expressed by normal cells, in particular by altered glycosylation. Structurally defined tumor associated MUC1 cannot be isolated from tumor cells. We synthesized MUC1 glycopeptide vaccines and analyzed their structure-activity relationships in immunizations; a monoclonal antibody that specifically distinguishes between human normal and tumor epithelial cells was thus generated. PMID- 26800385 TI - Solution structure of the calmodulin-like C-terminal domain of Entamoeba alpha actinin2. AB - Cell motility is dependent on a dynamic meshwork of actin filaments that is remodelled continuously. A large number of associated proteins that are severs, cross-links, or caps the filament ends have been identified and the actin cross linker alpha-actinin has been implied in several important cellular processes. In Entamoeba histolytica, the etiological agent of human amoebiasis, alpha-actinin is believed to be required for infection. To better understand the role of alpha actinin in the infectious process we have determined the solution structure of the C-terminal calmodulin-like domain using NMR. The final structure ensemble of the apo form shows two lobes, that both resemble other pairs of calcium-binding EF-hand motifs, connected with a mobile linker. PMID- 26800386 TI - Long-term cancer risk after hysterectomy on benign indications: Population-based cohort study. AB - Hysterectomy on benign indications is associated with an increased risk for adverse health effects. However, little is known about the association between hysterectomy and subsequent cancer occurrence later in life. The purpose of this study was to assess the effect of hysterectomy on the incidence of cancer. In this population-based cohort study, we used data on 111,595 hysterectomized and 537,9843 nonhysterectomized women from nationwide Swedish Health Care registers including the Inpatient Register, the Cancer Register and the Cause of Death Register between 1973 and 2009. Hysterectomy with or without concomitant bilateral salpingo-ophorectomy (BSO) performed on benign indications was considered as exposure and incidence of primary cancers was used as outcome measure. Rare primary cancers (<100 cases for the two groups combined) were excluded from analysis. A marginal risk reduction for any cancer was observed for women with previous hysterectomy and for those with hysterectomy and concurrent BSO (HR 0.93, 95% CI 0.91-0.95 and HR 0.92, 95% CI 0.87-0.96, respectively). Compared to nonhysterectomized women, significant risks were observed for thyroid cancer (HR 1.76, 95% CI 1.45-2.14). For both hysterectomy and hysterectomy with BSO, an association with brain cancer was observed (HR 1.48, 95% CI 1.32-1.65 and HR 1.45, 95% CI 1.15-1.83, respectively). Hysterectomy, with or without BSO, was not associated with breast, lung or gastrointestinal cancer. We conclude that hysterectomy on benign indications is associated with an increased risk for thyroid and brain cancer later in life. Further research efforts are needed to identify patient groups at risk of malignancy following hysterectomy. PMID- 26800388 TI - Bio-oil production via catalytic pyrolysis of Anchusa azurea: Effects of operating conditions on product yields and chromatographic characterization. AB - Pyrolysis of Anchusa azurea, a lignocellulosic gramineous plant, was carried out in a tubular, fixed-bed reactor in the presence of four catalysts (Ca(OH)2, Na2CO3, ZnCl2, Al2O3). The influences of pyrolysis parameters such as catalyst and temperature on the yields of products were studied. It was found that higher temperature resulted in lower liquid (bio-oil) and solid (bio-char) yields and higher gas yields. Catalysts effected the yields of products differently and the composition of bio-oils. Liquid yields were increased in the presence of Na2CO3, ZnCl2 and Al2O3 and decreased with Ca(OH)2. The highest bio-oil yield (34.05%) by weight including aqueous phase was produced with Na2CO3 catalyst at 450 degrees C. The yields of products (bio-char, bio-oil and gas) and the compositions of the resulting bio-oils were determined by GC-MS, FT-IR and elemental analysis. GC-MS identified 124 and 164 different compounds in the bio-oils obtained at 350 and 550 degrees C respectively. PMID- 26800389 TI - Surgical therapy of single peri-implantitis intrabony defects, by means of deproteinized bovine bone mineral with 10% collagen. AB - AIM: To evaluate the efficacy of a reconstructive surgical procedure in single peri-implantitis infrabony defects. METHODS: Seventy-five patients with one peri implantitis crater-like lesion with pocket depth (PD) >= 6 mm, were included. Each defect was assigned to one characteristic class, by an independent examiner. After implant decontamination, defects were filled with deproteinized bovine bone mineral with 10% collagen. RESULTS: At 1-year follow-up, four patients were lost and six implants removed. Treatment success, PD <= 5 mm and absence of suppuration/bleeding on probing (BOP), was obtained in 37 (52.1%) of the 71 implants examined. PD was significantly reduced by 2.92 +/- 1.73 mm (p < 0.0001). BOP decreased from 71.5 +/- 34.4% to 18.3 +/- 28.6% (p < 0.0001). The mean number of deep pockets (>= 6 mm) decreased from 3.00 +/- 0.93 to 0.85 +/- 1.35 (p < 0.0001). CONCLUSIONS: These results confirm the possibility to successfully treat peri-implantitis lesions. There is lack of evidence of whether or not the resolution of the peri-implant disease is associated with the defect configuration. Due to the fact that complete resolution does not seem a predictable outcome, the clinical decision on whether implants should be treated should be based on several patient related elements. PMID- 26800390 TI - Skin biopsy in assessing meralgia paresthetica. AB - INTRODUCTION: Meralgia paresthetica is a focal neuropathy caused by compression of the lateral femoral cutaneous nerve (LFCN). The disease can be difficult to assess by neurophysiological or imaging studies. METHODS: We studied 5 patients who presented to our neuromuscular clinic from April 2012 to December 2014 with a clinical suspicion of meralgia paresthetica and had skin biopsies with intraepidermal nerve fiber density (IENFD) evaluation. RESULTS: The mean age at onset was 37.2 (range 21-59) years. There were 4 women and 1 man. Two were obese, 2 wore tight jeans, and 1 had mild diabetes mellitus. IENFD was reduced in the symptomatic proximal thigh in all 5 patients and was also reduced in the asymptomatic thigh in 2 patients. It was normal in the distal leg in 4 patients. CONCLUSION: Meralgia paresthetica is associated with loss of small intraepidermal nerve fibers. Skin biopsy with IENFD evaluation may be a useful diagnostic tool for this disease. PMID- 26800391 TI - Ligand-Protein Affinity Studies Using Long-Lived States of Fluorine-19 Nuclei. AB - The lifetimes TLLS of long-lived states or TLLC of long-lived coherences can be used for the accurate determination of dissociation constants of weak protein ligand complexes. The remarkable contrast between signals derived from LLS or LLC in free and bound ligands can be exploited to search for weak binders with large dissociation constants KD > 1 mM that are important for fragment-based drug discovery but may escape detection by other screening techniques. Alternatively, the high sensitivity of the proposed method can be exploited to work with large ligand-to-protein ratios, with an evident advantage of reduced consumption of precious proteins. The detection of (19)F-(19)F long-lived states in suitably designed fluorinated spy molecules allows one to perform competition binding experiments with high sensitivity while avoiding signal overlap that tends to hamper the interpretation of proton spectra of mixtures. PMID- 26800392 TI - Riluzole combination therapy for moderate-to-severe major depressive disorder: A randomized, double-blind, placebo-controlled trial. AB - Recent evidences suggest that glutamatergic dysregulation implicated in neural plasticity and cellular resilience may contribute to the pathophysiology of Major Depressive Disorder (MDD). Riluzole, which exerts its effect by targeting glutamate neurotransmission, has shown antidepressant effect in recent preclinical, observational and open label studies. This study aimed to assess the efficacy and tolerability of riluzole in patients with MDD. Sixty-four inpatients with diagnosis of moderate to severe major depressive disorder participated in a parallel, randomized, controlled trial, and sixty patients underwent 6 weeks treatment with either riluzole (50 mg/bid) plus citalopram (40 mg/day) or placebo plus citalopram (40 mg/day). All participants were inpatients for the whole duration of the study. Patients were assessed using Hamilton depression rating scale (HDRS) at baseline and weeks 2, 4 and 6. The primary outcome measure was to assess the efficacy of riluzole compared to placebo in improving the depressive symptoms. General linear model repeated measures demonstrated significant effect for time * treatment interaction on HDRS [F (1.86, 107.82) = 8.63, p < 0.001]. Significantly greater improvement was observed in HDRS scores in the riluzole group compared to the placebo group from baseline HDRS score at weeks 2, 4 and 6 (p < 0.001, p = 0.001, p = 0.002, respectively). Significantly greater response with greater speed to treatment was observed in the riluzole group than the placebo group. No serious adverse event occurred. This study showed a favorable safety and efficacy profile in patients with major depressive disorder. Larger controlled studies with longer treatment periods are needed to investigate long term safety, efficacy and optimal dosing. PMID- 26800393 TI - TAK-228 (formerly MLN0128), an investigational oral dual TORC1/2 inhibitor: A phase I dose escalation study in patients with relapsed or refractory multiple myeloma, non-Hodgkin lymphoma, or Waldenstrom's macroglobulinemia. AB - The PI3K/AKT/mTOR signaling pathways are frequently dysregulated in multiple human cancers, including multiple myeloma (MM), non-Hodgkin lymphoma (NHL), and Waldenstrom's macroglobulinemia (WM). This was the first clinical study to evaluate the safety, tolerability, maximal-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics, and preliminary clinical activity of TAK-228, an oral TORC1/2 inhibitor, in patients with MM, NHL, or WM. Thirty-nine patients received TAK-228 once daily (QD) at 2, 4, 6, or 7 mg, or QD for 3 days on and 4 days off each week (QDx3d QW) at 9 or 12 mg, in 28-day cycles. The overall median age was 61.0 years (range 46-85); 31 patients had MM, four NHL, and four WM. Cycle 1 DLTs occurred in five QD patients (stomatitis, urticaria, blood creatinine elevation, fatigue, and nausea and vomiting) and four QDx3d QW patients (erythematous rash, fatigue, asthenia, mucosal inflammation, and thrombocytopenia). The MTDs were determined to be 4 mg QD and 9 mg QDx3d QW. Thirty-six patients (92%) reported at least one drug-related toxicity; the most common grade >=3 drug-related toxicities were thrombocytopenia (15%), fatigue (10%), and neutropenia (5%). TAK-228 exhibited a dose-dependent increase in plasma exposure and no appreciable accumulation with repeat dosing; mean plasma elimination half-life was 6-8 hr. Of the 33 response-evaluable patients, one MM patient had a minimal response, one WM patient achieved partial response, one WM patient had a minor response, and 18 patients (14 MM, two NHL, and two WM) had stable disease. These findings encourage further studies including combination strategies. PMID- 26800394 TI - Interobserver agreement of multicompartment ultrasound in the assessment of pelvic floor anatomy. AB - OBJECTIVE: To assess the interobserver agreement of pelvic floor anatomical measurements using multicompartment pelvic floor ultrasound. METHODS: Females were recruited from the urogynaecology/gynaecology clinics between July and October 2009 and underwent multicompartment pelvic floor ultrasonography (PFUS) using two-dimensional (2D) transperineal ultrasound (TPUS), high-frequency 2D/three-dimensional (3D) endovaginal ultrasound (EVUS) using a biplane probe with linear and transverse arrays and a 360 degrees rotational 3D-EVUS. PFUS measurements were independently analysed by two clinicians. RESULTS: 158 females had PFUS assessment. Good-to-excellent interobserver agreement was observed for bladder-symphysis distance at rest and valsalva, urethral thickness, urethral length, urethral volume, levator hiatus area and width, anteroposterior diameter and anorectal angle. Lins Correlation was used to calculate the interobserver agreement and Bland-Altman plots were created to demonstrate the agreement between the researchers. There was also a good-to-excellent agreement between the two clinicians for the assessment of pelvic organ prolapse (POP) in the anterior, middle and posterior compartment. CONCLUSION: Multicompartment PFUS is a reliable tool in the anatomical assessment of pelvic floor measurements and POP. ADVANCES IN KNOWLEDGE: We found a good-to-excellent agreement between the two assessors in the assessment of pelvic floor measurements for all three pelvic floor compartments and suggest that multicompartment PFUS could be considered as a systematic integrated approach to assess the pelvic floor. PMID- 26800396 TI - Seeing is Believing? An Examination of Perceptions of Local Weather Conditions and Climate Change Among Residents in the U.S. Gulf Coast. AB - What role do objective weather conditions play in coastal residents' perceptions of local climate shifts and how do these perceptions affect attitudes toward climate change? While scholars have increasingly investigated the role of weather and climate conditions on climate-related attitudes and behaviors, they typically assume that residents accurately perceive shifts in local climate patterns. We directly test this assumption using the largest and most comprehensive survey of Gulf Coast residents conducted to date supplemented with monthly temperature data from the U.S. Historical Climatology Network and extreme weather events data from National Climatic Data Center. We find objective conditions have limited explanatory power in determining perceptions of local climate patterns. Only the 15- and 19-year hurricane trends and decadal summer temperature trend have some effects on perceptions of these weather conditions, while the decadal trend of total number of extreme weather events and 15- and 19-year winter temperature trends are correlated with belief in climate change. Partisan affiliation, in contrast, plays a powerful role affecting individual perceptions of changing patterns of air temperatures, flooding, droughts, and hurricanes, as well as belief in the existence of climate change and concern for future consequences. At least when it comes to changing local conditions, "seeing is not believing." Political orientations rather than local conditions drive perceptions of local weather conditions and these perceptions-rather than objectively measured weather conditions-influence climate-related attitudes. PMID- 26800395 TI - Calculation of cut-off values based on the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Pemphigus Disease Area Index (PDAI) pemphigus scoring systems for defining moderate, significant and extensive types of pemphigus. AB - BACKGROUND: Two pemphigus severity scores, Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Pemphigus Disease Area Index (PDAI), have been proposed to provide an objective measure of disease activity. However, the use of these scores in clinical practice is limited by the absence of cut-off values that allow differentiation between moderate, significant and extensive types of pemphigus. OBJECTIVES: To calculate cut-off values defining moderate, significant and extensive pemphigus based on the ABSIS and PDAI scores. METHODS: In 31 dermatology departments in six countries, consecutive patients with newly diagnosed pemphigus were assessed for pemphigus severity, using ABSIS, PDAI, Physician's Global Assessment (PGA) and Dermatology Life Quality Index (DLQI) scores. Cut-off values defining moderate, significant and extensive subgroups were calculated based on the 25th and 75th percentiles of the ABSIS and PDAI scores. The median ABSIS, PDAI, PGA and DLQI scores of the three severity subgroups were compared in order to validate these subgroups. RESULTS: Ninety-six patients with pemphigus vulgaris (n = 77) or pemphigus foliaceus (n = 19) were included. The median PDAI activity and ABSIS total scores were 27.5 (range 3-84) and 34.8 points (range 0.5-90.5), respectively. The respective cut-off values corresponding to the first and third quartiles of the scores were 15 and 45 for the PDAI, and 17 and 53 for ABSIS. The moderate, significant and extensive subgroups were thus defined, and had distinguishing median ABSIS (P < 0.001), PDAI (P < 0.001), PGA (P < 0.001) and DLQI (P = 0.03) scores. CONCLUSIONS: This study suggests cut-off values of 15 and 45 for PDAI and 17 and 53 for ABSIS, to distinguish moderate, significant and extensive pemphigus forms. Identifying these pemphigus activity subgroups should help physicians to classify and manage patients with pemphigus. PMID- 26800398 TI - Providing Culturally Appropriate Care to American Muslims With Cancer. AB - Worldwide, Islam is the second most populous religion and, in many countries in the Middle East, South and Southeast Asia, and Africa, it is the predominant religion. The population of Muslims in the United States is projected to dramatically increase in the next few decades. Understanding the role of Islam for people who believe in and follow Islam-Muslims-will provide nurses with important perspectives that affect health behaviors, cancer screening, treatment decision-making, and end-of-life care.?. PMID- 26800397 TI - miR-222 attenuates cisplatin-induced cell death by targeting the PPP2R2A/Akt/mTOR Axis in bladder cancer cells. AB - Increased miR-222 levels are associated with a poor prognosis in patients with bladder cancer. However, the role of miR-222 remains unclear. In the present study, we found that miR-222 enhanced the proliferation of both the T24 and the 5637 bladder cancer cell lines. Overexpression of miR-222 attenuated cisplatin induced cell death in bladder cancer cells. miR-222 activated the Akt/mTOR pathway and inhibited cisplatin-induced autophagy in bladder cancer cells by directly targeting protein phosphatase 2A subunit B (PPP2R2A). Blocking the activation of Akt with LY294002 or mTOR with rapamycin significantly prevented miR-222-induced proliferation and restored the sensitivity of bladder cancer cells to cisplatin. These findings demonstrate that miR-222 modulates the PPP2R2A/Akt/mTOR axis and thus plays a critical role in regulating proliferation and chemotherapeutic drug resistance. Therefore, miR-222 may be a novel therapeutic target for bladder cancer. PMID- 26800399 TI - Patients' Perspectives on Creating a Personal Safety Net During Chemotherapy. AB - Nurses are critical to the physical management and psychological support of patients undergoing chemotherapy, which is a vulnerable time for many. This article presents the results of a qualitative study intended to explore the experience of Japanese patients with breast cancer during chemotherapy, including the finding that participants created personal safety nets in physical, emotional, and social contexts that helped them to gain confidence in their ability to exert control over their lives. Understanding each patient's personal safety net allows nurses to support their patients in maintaining and improving their function and well-being. PMID- 26800400 TI - Reliably Addressing "What Matters" Through a Quality Improvement Process. AB - Oncology nurses have a critical role in mitigating the intense vulnerability, loss of control, and fear of the unknown that characterizes the experiences of patients with cancer and their family members. Reliably inquiring about the issues that are at the forefront for patients and their loved ones can encourage a deeper dialogue-where nurses can understand and address the issues that are most important to them. A practical quality improvement approach can help to ensure that processes are in place to assist nurses in devoting time to reliably inquire about "what matters" to each patient at every encounter. PMID- 26800401 TI - Central Line-Associated Bloodstream Infection Prevention: Standardizing Practice Focused on Evidence-Based Guidelines. AB - Central venous access devices (CVADs) are integral to the treatment and provision of supportive care for many patients with cancer. Central venous catheters are the most frequent cause of healthcare-associated bloodstream infections. Healthcare-associated bloodstream infections can be prevented when evidence-based practices are followed consistently over time. Establishing nursing best practice with CVADs in the ambulatory setting presents additional challenges because of multiple providers, caregivers, and policies. This article identifies evidence based practice strategies implemented at a comprehensive ambulatory cancer center to standardize best nursing practice for central lines.?. PMID- 26800402 TI - Telemedicine in Oncology. AB - For patients who have difficulty traveling to a clinic or doctor's office because of living in a remote location or lack of transportation, increasing opportunities exist to access health care remotely. Telemedicine is a growing field that has potential benefits for patients, providers, and the healthcare system.?. PMID- 26800403 TI - Nursing Care of Patients Undergoing Chemotherapy Desensitization: Part I. AB - Hypersensitivity reactions to chemotherapeutic agents can cause the discontinuation of first-line therapies. Chemotherapy desensitization is a safe, but labor-intensive, process to administer these important medications. A desensitization protocol can enable a patient to receive the entire target dose of a medication, even if the patient has a history of severe infusion reactions. In this article, the authors explain the pathophysiology of hypersensitivity reactions and describe the recent development of desensitization protocols in oncology. In part II of this article, which will appear in the April 2016 issue of the Clinical Journal of Oncology Nursing, the authors will give a detailed account of how a desensitization protocol is performed at an academic medical center.?. PMID- 26800404 TI - Providing Novice Navigators With a GPS for Role Development: Oncology Nurse Navigator Competency Project. AB - BACKGROUND: The care of patients with cancer has evolved to include various lay and professional roles to enhance care coordination with the focus on delivering patient-centered care. Oncology nurses in the role of oncology nurse navigators (ONNs) contribute to the delivery of patient-centered care by guiding patients and families through the cancer continuum and providing resources to overcome system and practical barriers and to enhance psychosocial support and cancer specific education. However, the role of the ONN is often defined differently depending on the practice setting and institutional policy. The result is an inconsistent assortment of role functions and educational backgrounds. OBJECTIVES: This article aims to promote standardization of the role of the ONN as well as the structure and boundaries of how ONNs function. METHODS: A project team was established by the Oncology Nursing Society to develop a professional practice framework and to identify core competencies for use by ONNs across a variety of practice settings. FINDINGS: The development of core competencies as well as examples of how the core competencies can be applied to ONN practice will help to define the ONN role and better serve the needs of patients with cancer, their families, and their caregivers. PMID- 26800405 TI - Fertility Preservation Before Cancer Treatment: Options, Strategies, and Resources. AB - BACKGROUND: Loss of fertility is one of the many potential late effects of cancer treatment. For young men and women who have not yet started or completed building their families, this can be a source of considerable emotional distress. Advances in reproductive technology can enable many of these patients to preserve their fertility; however, discussions must be initiated early enough during treatment planning to enable them to take advantage of these options. OBJECTIVES: The purpose of this article is to provide oncology nurses with information, strategies, and resources to discuss fertility with men and women starting cancer treatment. METHODS: This article summarizes the literature on treatment-related fertility risks and fertility preservation options, and provides a systematic framework for nurses to integrate these discussions into practice. FINDINGS: Oncology nurses can effectively collaborate with other members of the healthcare team to ensure that young men and women starting cancer treatment are informed of the potential risks to fertility from their planned treatment, understand options to preserve fertility before treatment, and, if interested, are referred to appropriate reproductive specialists. PMID- 26800406 TI - Planning and Implementation of Low-Dose Computed Tomography Lung Cancer Screening Programs in the United States. AB - BACKGROUND: One of the largest, most expensive randomized, controlled trials, the National Lung Screening Trial, found that annual low-dose computed tomography (LDCT) scans led to a 20% reduction in lung cancer deaths. OBJECTIVES: This study describes the characteristics and program implementation barriers experienced by LDCT screening programs in the United States. METHODS: Using a mixed-methods approach, Lung Cancer Alliance Screening Centers of Excellence were surveyed and interviewed in 2013. Representatives from 65 centers completed an electronic questionnaire, followed by in-depth interviews with 13 physicians and nurse navigators regarding their institution's screening programs. FINDINGS: Participants cited low patient demand and few physician referrals as barriers, but few centers reported needing additional staff or equipment. Those interviewed discussed the importance of a multidisciplinary team and overcoming barriers related to insurance reimbursement, costs, and physician knowledge to improve program implementation. PMID- 26800408 TI - Establishing an Inpatient Gym for Recipients of Stem Cell Transplantation: A Multidisciplinary Collaborative. AB - BACKGROUND: Evidence suggests that exercise can have a profound impact on physiologic and quality-of-life outcomes for patients undergoing hematopoietic stem cell transplantation (HSCT). Despite this, implementation of a gym on inpatient HSCT units may be limited because of space, infrastructure, and budget. OBJECTIVES: This article presents the design, implementation, and evaluation of the gym and highlights its use for individual and group patient activities. METHODS: An interprofessional team at a National Cancer Institute-designated comprehensive cancer center collaborated to design and implement gym space on an inpatient HSCT unit servicing as many as 86 beds. FINDINGS: Informal feedback from patients, as well as metrics on use of the space, indicates that the gym is well received and frequently used. Limitations include the absence of a designated physical therapy technician to supervise individual activity, which may limit patient access when a staff member is unavailable. The cost associated with the implementation of such space may be offset by benefits to patients, including enhanced conditioning, quality of life, and time to discharge, as evidenced in the literature. PMID- 26800407 TI - Improving Patient Safety With Error Identification in Chemotherapy Orders by Verification Nurses. AB - BACKGROUND: The prevalence of medication errors associated with chemotherapy administration is not precisely known. Little evidence exists concerning the extent or nature of errors; however, some evidence demonstrates that errors are related to prescribing. This article demonstrates how the review of chemotherapy orders by a designated nurse known as a verification nurse (VN) at a National Cancer Institute-designated comprehensive cancer center helps to identify prescribing errors that may prevent chemotherapy administration mistakes and improve patient safety in outpatient infusion units. OBJECTIVES: This article will describe the role of the VN and details of the verification process. METHODS: To identify benefits of the VN role, a retrospective review and analysis of chemotherapy near-miss events from 2009-2014 was performed. FINDINGS: A total of 4,282 events related to chemotherapy were entered into the Reporting to Improve Safety and Quality system. A majority of the events were categorized as near-miss events, or those that, because of chance, did not result in patient injury, and were identified at the point of prescribing. PMID- 26800409 TI - Implementation of Medical Orders for Life-Sustaining Treatment. AB - BACKGROUND: When an outpatient in a northeastern cancer institute requested a Medical Orders for Life-Sustaining Treatment (MOLST) form, the state's approved resuscitation form in all settings, none were available. A project was undertaken to institute MOLST forms into policy and routine practice. Research supports early discussions of end-of-life care in patients with cancer and the use of MOLST as an effective tool. OBJECTIVES: The purpose of this article is to discuss the initiation and facilitation of MOLST implementation into practice and policy at a cancer institute. METHODS: Introducing, overcoming resistance to, piloting, and adopting MOLST in an oncology setting is reported and explained based on the three stages of Lewin's Theory of Planned Change. FINDINGS: A small pilot of MOLST with palliative care providers demonstrated the feasibility and suitability of using MOLST in the oncology setting. MOLST was adopted into policy and routine practice at the cancer institute. PMID- 26800410 TI - Cervical Cancer Screening in Developing Countries: Using Visual Inspection Methods. AB - BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide. Most diagnoses occur in developing countries where cases are detected in later stages with poorer prognoses. Cervical cancer is a preventable disease; however, most women in developing and resource-limited countries do not have the access to the same methods of cervical cancer screening as women in developed countries. OBJECTIVES: The objectives of this review are to examine and discuss (a) the burden of cervical cancer in developing countries, (b) the socioeconomic determinants of primary and secondary prevention of cervical cancer, and (c) the use of visual inspection methods of screening with acetic acid (VIA) and Lugol's iodine (VILI) as alternative strategies for cervical cancer screening in areas with limited resources. METHODS: A critical review was conducted of the literature and recommendations on the role of VIA in cervical cancer prevention in developing countries. FINDINGS: Visual inspection methods of screening for cervical cancer have emerged as a low-cost, safe, and effective alternative to cytology screening and can be administered to a large proportion of targeted women in developing countries. VIA and VILI can be performed by nurses, midwives, and paramedic staff after a short competency-based training program. In addition, visual screening provides immediate results in real time, permitting a single visit, screen-and-treat approach, which is an effective strategy to overcome issues of nonadherence to follow-up visits among women in developing countries. PMID- 26800411 TI - Tailoring Education to Perceived Fall Risk in Hospitalized Patients With Cancer: A Randomized, Controlled Trial. AB - BACKGROUND: Patients with cancer carry a higher risk for falls, potentially resulting in increased morbidity, mortality, and financial costs, as well as lower quality of life. Few evidence-based interventions are tailored to the patient's perception of risk for falls. OBJECTIVES: This study aimed to determine the effect of tailored, nurse-delivered interventions as compared to a control group on patient perception of risk for falls, confidence in fall prevention, and willingness to ask for assistance. METHODS: A two-group, prospective, randomized, controlled design was used to test the intervention in a convenience sample of 91 patients on an adult bone marrow transplantation unit. The intervention consisted of video and printed education tailored to the nurse's risk assessment and the patient's perception of risk. Patient's self-reported perception, confidence, and willingness were measured at three time points. FINDINGS: About one-third of patients perceived themselves to be at low risk for falls despite a nurse rating of high risk. A statistically significant difference existed in the proportion of patients who perceived themselves to be at high risk for falls pre- and postintervention (p = 0.01). Results suggest that tailoring education to the patients' perceived risk for falls can help patients become more aware of fall risk. PMID- 26800412 TI - Controlling Malglycemia in Patients Undergoing Treatment for Cancer. AB - Patients with or without preexisting diabetes undergoing treatment for cancer may be at risk for malglycemic events. Malglycemia, particularly hyperglycemia and diabetes in patients with cancer, may lead to adverse outcomes. Prevention, prompt recognition, and early intervention to regulate malglycemia can optimize the effects of cancer treatment, minimize the harmful consequences, and improve quality of life for patients with cancer. The development of evidence-based standards of care and protocols are needed to guide clinical practice when caring for patients with cancer. PMID- 26800413 TI - Presumed Glioblastoma Multiforme: A Case for Biopsy Prior to Treatment. AB - Glioblastoma multiforme (GBM) is the most lethal and aggressive primary brain tumor. Several other abnormalities (neoplastic, infectious, or vascular) can mimic symptoms seen with GBM. This article reviews GBM and presents a case study that demonstrates the rationale for biopsy and pathologic diagnosis prior to the initiation of treatment for malignant brain tumors. PMID- 26800414 TI - Development of a Workshop for Malignant Hematology Nursing Education. AB - As part of a comprehensive orientation for nurses caring for patients with hematologic malignancies, nurses are expected to attend general corporate orientation immediately followed by hospital site-specific nursing orientation. The orientation is comprised of lectures, e-learning, and clinical observership, as well as clinical practice under supervision of a preceptor. Nurses also are expected to attend foundational courses. The goal of these courses is to consolidate practical and theoretical knowledge in a specific oncology nursing specialty. A workshop was developed that offers a unique vision by interweaving theory, practice, and patient voice.?. PMID- 26800415 TI - The Impact of a Knitting Intervention on Compassion Fatigue in Oncology Nurses. AB - Compassion fatigue is the emotional exhaustion and stress that nurses can feel when caring for terminally ill patients. This can contribute to high nursing turnover rates, result in poor job satisfaction, and lead to decreased ability to provide quality care. Oncology nurses are vulnerable to compassion fatigue because they develop relationships with patients battling life-threatening illnesses, provide end-of-life care, and encounter ethical dilemmas related to cancer treatment. ?. PMID- 26800417 TI - Hospice and Palliative Care: Development and Challenges in China. AB - BACKGROUND: Terminally ill patients can benefit from palliative care, including relief from physical and emotional suffering, improved quality of life, and longer survival rates. However, despite marked development in other countries, palliative care is still in its infancy in China. OBJECTIVES: The general population and healthcare professionals in China have yet to realize the importance of palliative care services. This article describes the status of palliative care services in China, the historic development of palliative care, and the barriers to its advancement. METHODS: The status quo of hospice and palliative care in China is reviewed, and suggestions are provided on how nurses can improve their abilities to care for patients with cancer at the end of life. FINDINGS: A significant amount of work is needed in China to meet the standards of international palliative care societies. Palliative care training for nurses is still very limited. Nurses and other health providers who are engaged in palliative care should be well trained regarding the principles and procedures of palliative care to ensure quality care. PMID- 26800418 TI - Physical Exercise and Cancer-Related Fatigue in Hospitalized Patients: Role of the Clinical Nurse Leader in Implementation of Interventions. AB - BACKGROUND: Guidelines suggest that aerobic endurance training and moderate resistance training lessen the effects of cancer-related fatigue (CRF). However, specifics regarding frequency, intensity, and type of physical activity required to alleviate fatigue are less specific. In addition, outcomes of these interventions during the initial stages of active treatment are not well documented. OBJECTIVES: The purpose of this article is to review the current evidence-based literature regarding the effects of physical exercise on CRF and the role that the clinical nurse leader (CNL) can play in implementing interventions to address CRF and promote physical exercise to improve patient outcomes. METHODS: A literature review of the effect of physical exercise on CRF was conducted using the CINAHL(r), PubMed, and Google Scholar databases. FINDINGS: As leaders in health care, CNLs have the knowledge and skill to take an active role in managing CRF and to develop evidence-based interventions to address fatigue in this patient population. Interventions may include creating and evaluating individualized exercise plans for inpatients with cancer and/or developing educational programs for the inpatient setting that may be continued after discharge and during outpatient treatment. PMID- 26800419 TI - Surgical Oncology: Evolution of Postoperative Fatigue and Factors Related to Its Severity. AB - BACKGROUND: Fatigue has been reported by many patients undergoing surgery and is associated with a negative prognosis. The factors associated with postoperative fatigue and its evolution during the postoperative period are unclear. Adequate fatigue measurement instruments are necessary to obtain reliable evaluations and to direct effective care to control fatigue in this patient population. OBJECTIVES: This article describes the evolution of postoperative fatigue in patients with cancer as well as related factors. METHODS: A review of the literature using the CINAHL(r) and PubMed databases was undertaken. FINDINGS: The prevalence of moderate and severe fatigue varies during the postoperative period, with a reduction in the 12 months after surgery. Various factors (e.g., stress, anxiety, depression, pain, changes in sleep patterns) seem to influence the severity of fatigue. More evidence is needed to explore the relationship between immediate postoperative fatigue and the evolution of fatigue during the period following surgical treatment for cancer. PMID- 26800420 TI - Piloting an Automated Distress Management Program in an Oncology Practice. AB - BACKGROUND: New administrative requirements to provide assessment and treatment for distress in patients with cancer, as well as concern for positive patient outcomes, highlight oncology practitioners' need for a high-quality distress management program. OBJECTIVES: Researchers designed, developed, implemented, and evaluated a nurse-led quality-improvement project that pilot tested a distress management program in an outpatient medical oncology practice. METHODS: The program used a tablet computer for data collection, immediate analysis, and recommendation display to provide individually tailored psychosocial coping recommendations, referrals, or both to nurses and patients. FINDINGS: Pre- and postprogram evaluations suggest that the program is feasible, safe, and effective for detecting and reducing distress in patients with cancer. In addition, tailoring psychosocial coping strategies to the patient's emotional situation may have been key to the program's effectiveness. PMID- 26800421 TI - Full-thickness porcine burns infected with Staphylococcus aureus or Pseudomonas aeruginosa can be effectively treated with topical antibiotics. AB - Burn and blast injuries are frequently complicated by invasive infections, which lead to poor wound healing, delay in treatment, disability, or death. Traditional approach centers on early debridement, fluid resuscitation, and adjunct intravenous antibiotics. These modalities often prove inadequate in burns, where compromised local vasculature limits the tissue penetration of systemic antibiotics. Here, we demonstrate the treatment of infected burns with topical delivery of ultrahigh concentrations of antibiotics. Standardized burns were inoculated with Staphylococcus aureus or Pseudomonas aeruginosa. After debridement, burns were treated with either gentamicin (2 mg/mL) or minocycline (1 mg/mL) at concentrations greater than 1,000 times the minimum inhibitory concentration. Amount of bacteria was quantified in tissue biopsies and wound fluid following treatment. After six days of gentamicin or minocycline treatment, S. aureus counts decreased from 4.2 to 0.31 and 0.72 log CFU/g in tissue, respectively. Similarly, P. aeruginosa counts decreased from 2.5 to 0.0 and 1.5 log CFU/g in tissue, respectively. Counts of both S. aureus and P. aeruginosa remained at a baseline of 0.0 log CFU/mL in wound fluid for both treatment groups. The findings here demonstrate that super-therapeutic concentrations of antibiotics delivered topically can rapidly reduce bacterial counts in infected full-thickness porcine burns. This treatment approach may aid wound bed preparation and accelerate time to grafting. PMID- 26800422 TI - Neonatal vascularization and oxygen tension regulate appropriate perinatal renal medulla/papilla maturation. AB - Congenital medullary dysplasia with obstructive nephropathy is a common congenital disorder observed in paediatric patients and represents the foremost cause of renal failure. However, the molecular processes regulating normal papillary outgrowth during the postnatal period are unclear. In this study, transcriptional profiling of the renal medulla across postnatal development revealed enrichment of non-canonical Wnt signalling, vascular development, and planar cell polarity genes, all of which may contribute to perinatal medulla/papilla maturation. These pathways were investigated in a model of papillary hypoplasia with functional obstruction, the Crim1(KST264/KST264) transgenic mouse. Postnatal elongation of the renal papilla via convergent extension was unaffected in the Crim1(KST264/KST264) hypoplastic renal papilla. In contrast, these mice displayed a disorganized papillary vascular network, tissue hypoxia, and elevated Vegfa expression. In addition, we demonstrate the involvement of accompanying systemic hypoxia arising from placental insufficiency, in appropriate papillary maturation. In conclusion, this study highlights the requirement for normal vascular development in collecting duct patterning, development of appropriate nephron architecture, and perinatal papillary maturation, such that disturbances contribute to obstructive nephropathy. PMID- 26800424 TI - Effects of Silymarin, Glycyrrhizin, and Oxymatrine on the Pharmacokinetics of Ribavirin and Its Major Metabolite in Rats. AB - The herb-derived compounds silymarin, glycyrrhizin, and oxymatrine are widely used to treat chronic hepatitis C virus infections in China. They are often prescribed in combination with ribavirin, which has a narrow therapeutic index. We investigated the influence of these compounds on ribavirin pharmacokinetics following concurrent administration at the human dose in rats. Pharmacokinetic parameters were determined in rats following oral (p.o.) administration of ribavirin (30 mg/kg) with or without silymarin (40 mg/kg, p.o.), glycyrrhizin (15 mg/kg, intraperitoneal [i.p.]), or oxymatrine (60 mg/kg, p.o.). Compared with the animals in ribavirin group, silymarin significantly decreased the area under the plasma concentration-time curve (AUC0-t ) and the peak plasma concentration (Cmax ) of ribavirin and ribavirin base by 31.2-44.5% and 48.9-50.0%, respectively. Glycyrrhizin significantly decreased the Cmax and AUC0-t of both ribavirin and its metabolite by 35.3-37.6% and 38.6-39.8%, respectively. However, silymarin or glycyrrhizin did not change the ribavirin metabolite/parent ratios of the AUC and Cmax . Oxymatrine did not induce significant changes in ribavirin concentration, but it significantly decreased the Cmax (26.6%) and AUC (21.8%) of the metabolite. This study indicates that the therapeutic efficacy of ribavirin may be compromised by the concurrent administration of herbal medicines/dietary supplements containing silymarin, glycyrrhizin, or oxymatrine. PMID- 26800425 TI - Systematic and quantitative assessment of the effect of chronic kidney disease on CYP2D6 and CYP3A4/5. AB - Recent reviews suggest that chronic kidney disease (CKD) can affect the pharmacokinetics of nonrenally eliminated drugs, but the impact of CKD on individual elimination pathways has not been systematically evaluated. In this study we developed a comprehensive dataset of the effect of CKD on the pharmacokinetics of CYP2D6- and CYP3A4/5-metabolized drugs. Drugs for evaluation were selected based on clinical drug-drug interaction (CYP3A4/5 and CYP2D6) and pharmacogenetic (CYP2D6) studies. Information from dedicated CKD studies was available for 13 and 18 of the CYP2D6 and CYP3A4/5 model drugs, respectively. Analysis of these data suggested that CYP2D6-mediated clearance is generally decreased in parallel with the severity of CKD. There was no apparent relationship between the severity of CKD and CYP3A4/5-mediated clearance. The observed elimination-route dependency in CKD effects between CYP2D6 and CYP3A4/5 may inform the need to conduct clinical CKD studies with nonrenally eliminated drugs for optimal use of drugs in patients with CKD. PMID- 26800426 TI - Lentivirus-TAZ Administration Alleviates Osteoporotic Phenotypes in the Femoral Neck of Ovariectomized Rats. AB - BACKGROUND: Osteoporosis is characterized by impairment of bone mass, strength, and microarchitecture, leading to the susceptibility to fragility fractures, especially in femoral neck region. Transcriptional coactivator with PDZ-binding motif (TAZ) facilitates osteogenesis while suppressing adipogenesis via regulation of transcriptional activities of runt-related transcription factor 2 and peroxisome proliferator-activated receptor x03B3;. Here, we validated the role of TAZ in vivo using an ovariectomized (OVX) rat model of osteoporosis. METHODS: Serum alkaline phosphatase, triglyceride, cholesterol and urinary hydroxyproline were measured on an automatic analyzer using diagnostic reagent kits. Serum OCN and C-terminal cross-linked telopeptides of type I collagen were measured using ELISA. Bone mineral density was measured using dual-energy X-ray scanner. Mechanical parameters were detected by three-point bending assays. Bone volume per tissue volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. No), and trabecular separation (Tb. Sp) were measured by MicroCT. The mRNA and protein levels were quantified by Realtime PCR and Western Blotting respectively. RESULTS: After injections of lentivirus overexpressing TAZ into the femoral neck region, bone mineral density, ultimate force, stiffness, BV/TV, Tb. Th, and Tb. No were significantly increased, whereas Tb. Sp was dramatically decreased. In the TAZ-overexpression region in the femoral neck of OVX rats, the mRNA levels of Runx2 and osteocalcin were obviously elevated, whereas that of PPARx03B3; and adipocyte protein 2 were downregulated. CONCLUSION: Lentivirus mediated TAZ gene therapy alleviated the osteoporotic phenotypes in the femoral neck of OVX rats, providing an alternative strategy for the treatment of postmenopausal osteoporosis and prevention of osteoporotic fracture. PMID- 26800427 TI - Effects of aging and sarcopenia on tongue pressure and jaw-opening force. AB - AIM: Aging and sarcopenia reduce not only body strength, but also the strength of swallowing muscles. We examined how aging and sarcopenia affect tongue pressure and jaw-opening force. METHODS: A total of 97 older adults (97 men, mean age 78.5 +/- 6.6 years; 100 women, mean age 77.8 +/- 6.2 years) were enrolled. Classification of sarcopenia was based on the Criteria of Asian Working Group for Sarcopenia. To investigate which variable between aging and sarcopenia was a significant independent variable on tongue pressure and jaw-opening force, multivariate linear regression analysis was carried out. RESULTS: The mean tongue pressure was 26.3 +/- 7.8 kPa in men and 24.6 +/- 7.2 kPa in women. The mean jaw opening force was 6.3 +/- 1.6 kg in men and 5.2 +/- 1.3 kg in women. Tongue pressure in men, aging and sarcopenia were significant independent variables, whereas only sarcopenia was a significant independent variable in women. Jaw opening force in men and sarcopenia were significant independent variables, whereas neither aging nor sarcopenia were significant independent variables in women. CONCLUSIONS: We found different characteristics in the effects of aging and sarcopenia based on site and sex. We suggested that aging decreased tongue pressure more than jaw-opening force, and affected men more than women. Sarcopenia affected tongue pressure and jaw-opening force, with the exception of jaw-opening force in women. Considering these characteristics is useful to predict the decline of swallowing function, and provide appropriate interventions preventing dysphagia. Geriatr Gerontol Int 2017; 17: 295-301. PMID- 26800428 TI - Psychological adjustment to cleft lip and/or palate: A narrative review of the literature. AB - OBJECTIVE: Adjustment to cleft lip and/or palate (CL/P) is multifaceted, involving several domains of psychological and social functioning. A substantial increase in research in this area has been evident in recent years, along with a preliminary shift in how adjustment to CL/P is conceptualised and measured. An updated and comprehensive review of the literature is needed in light of the rapidly expanding and changing field. DESIGN: A narrative review of 148 quantitative and qualitative studies published between January 2004 and July 2015. MAIN OUTCOME MEASURES: Findings are presented according to five key domains of adjustment: Developmental Trajectory, Behaviour, Emotional Well-being, Social Experiences and Satisfaction with Appearance and Treatment. Data pertaining to General Psychological Well-being were also examined. RESULTS: The overall impact of CL/P on psychological adjustment appears to be low. Nonetheless, the review demonstrates the complexity of findings both within and across domains, and highlights recurring methodological challenges. CONCLUSIONS: Research findings from the last decade are considered to be largely inconclusive, although some areas of emerging consensus and improvements in the approaches used were identified. Efforts to collect data from large, representative and longitudinal samples, which are comparable across studies and encompassing of the patient perspective, should be doubled. PMID- 26800429 TI - Digestive evaluation of soy isolate protein as affected by heat treatment and soy oil inclusion in broilers at an early age. AB - Soy protein isolate (SPI) mixed with soybean oil (SPIO) incubated at 100 degrees C for 8 h was used to evaluate changes of solubility and digestibility of SPI in vitro and digestive function in broilers at an early age. Arbor Acres broilers were allocated to three groups with six replicates of 12 birds, receiving basal diet (CON), 8 h heat-oxidized SPI diet (HSPI) and 8 h heat-oxidized mixture of SPI and 2% soybean oil diet (HSPIO) for 21 days, respectively. Nitrogen solubility index (NSI) declined and soybean oil accelerated the decline of NSI during incubation (P < 0.05). Decreased in vitro digestibility of dry matter (DM) and crude protein (CP) were observed in SPIO (P < 0.05). HSPI and HSPIO decreased body weight gain, relative jejunum weight and pancreatic trypsin activity at day 21 (P < 0.05). HSPIO decreased anterior intestinal trypsin activity at day 14 and amylase and trypsin activity at day 21, pancreatic amylase activity at day 21 and apparent digestibility of DM, organic matter and CP of broilers from days 18 to 20 (P < 0.05). Heat treatment and soybean oil could induce oxidative modification of SPI, and oxidized SPI negatively affected growth and digestion of broilers. (c) 2016 Japanese Society of Animal Science. PMID- 26800430 TI - Designed synthesis of fluorous-functionalized magnetic mesoporous microspheres for specific enrichment of phosphopeptides with fluorous derivatization. AB - In this work, for the first time, perfluorinated magnetic mesoporous microspheres were designed and synthesized for the highly specific enrichment of fluorous derivatized phosphopeptides through the unique fluorine-fluorine interactions. The perfluorinated magnetic mesoporous microspheres were prepared through a surfactant-mediated one-pot approach and successfully applied to the selective extraction of fluorous-derivatized phosphopeptides from beta-casein tryptic digest, protein mixtures, and human serum. Thanks to the hydrophilic silanol groups exposed on the surface, perfluorinated groups modified in the pore channels and the magnetic cores, the flourous-functionalized magnetic microspheres exhibited excellent dispersibility, specificity toward fluorous derivatized phosphopeptides while facilitated separation procedures. The novel composites achieved a high selectivity of 1:1000 toward nonphosphorylated peptides and proved to be practicable in the enrichment of endogenous phosphopeptides in the human serum sample. PMID- 26800431 TI - Cyclodextrin-based nanosponges: a versatile platform for cancer nanotherapeutics development. AB - Nanosponges (NSs) are a new age branched cyclodextrin (CD) polymeric systems exhibiting tremendous potential in pharmaceutical, agro science, and biomedical applications. Over the past decade, different varieties of NS based on the type of CD and the crosslinker have been developed tailored for specific applications. NS technology has been instrumental in achieving solubilization, stabilization, sustained release, enhancement of activity, permeability enhancement, protein delivery, ocular delivery, stimuli sensitive drug release, enhancement of bioavailability, etc. There is a major explosion of research in the area of NS aided cancer therapeutics. A wide of anticancer molecules both from a pharmacological and physicochemical perspective have been developed as NS formulations by several groups including ours. Our objective in this review is to capture a systematic and comprehensive snapshot of the state-of-the-art of NS aided cancer therapeutics reported so far. This review will provide an ideal platform for both the formulation scientists working on new polymeric/drug development and cancer biologists/scientists to understand the current nanotechnologies in CD-based NS-aided cancer therapeutics. The scope of the review is limited to small molecules and CD-based NS. The review covers in detail the problems associated with anticancer small molecules, and the solution provided by CD-based NS specifically for camptothecin, curcumin, paclitaxel, tamoxifen, resveratrol, quercetin, oxygen-NS, temozolomide, doxorubicin, and 5 Fluorouracil. WIREs Nanomed Nanobiotechnol 2016, 8:579-601. doi: 10.1002/wnan.1384 For further resources related to this article, please visit the WIREs website. PMID- 26800432 TI - Photo-Fenton degradation of the herbicide 2,4-D in aqueous medium at pH conditions close to neutrality. AB - A theoretical and experimental study of the photo-Fenton degradation of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) in water is presented. A kinetic model derived from a reaction sequence is proposed using the ferrioxalate complex as iron source for conditions of pH = 5. The kinetic model was employed to predict the concentrations of 2,4-D, 2,4-dichlorophenol (2,4-DCP), hydrogen peroxide (HP) and oxalate (Ox) in a flat plate laboratory reactor irradiated with a solar simulator. Two types of incident irradiation levels were tested by different combinations of attenuation filters. The effects of the oxalate/Fe(+3) molar ratio (Ox/Fe), the reaction temperature (T) and the 2,4-D/HP molar ratio (R) on the photo-Fenton process were also investigated. For low radiation level and operating conditions of R = 50 and T = 50 degrees C, a 2,4-D conversion of 95.6% was obtained after 180 min. Moreover, the 2,4-D conversion was almost 100% in only 120 min when the system was operated under the same operating conditions and high radiation level. From the proposed model and the experimental data, the corresponding kinetic parameters were estimated applying a nonlinear regression method. A good agreement between the kinetic model and experimental data, for a wide range of simulated solar operating conditions, was observed. For 2,4-D, 2,4 DCP, HP and Ox concentrations, the calculated RMSE were 1.21 * 10(-2), 5.45 * 10( 3), 2.86 * 10(-1) and 2.65 * 10(-2) mM, respectively. PMID- 26800433 TI - Measurement of liver iron concentration by superconducting quantum interference device biomagnetic liver susceptometry validates serum ferritin as prognostic parameter for allogeneic stem cell transplantation. AB - INTRODUCTION: There are conflicting data regarding the role of serum ferritin (SF) as surrogate parameter for iron overload as an independent prognostic factor for outcome after allogeneic stem cell transplantation (SCT). Superconducting quantum interference device (SQUID) biomagnetic liver susceptometry, a noninvasive measurement of iron overload, allows measurement of the interference of an exteriorly applied small but highly constant magnetic field by the paramagnetic liver storage iron. By measuring the true iron load of patients through SQUID, we wanted to assess the effect of iron overload on patients undergoing SCT. METHODS: We conducted a single-center retrospective analysis (1994-2010), comparing the effect of SF and liver iron content measured by SQUID shortly before transplantation on overall survival (OS), event-free survival (EFS), and transplant-related mortality (TRM) in 142 patients (median age 54.5 yr, range 5.6-75 yr) undergoing SCT (80% reduced intensity regimen). Patients were subdivided into five groups: myelodysplastic syndrome, de novo acute myeloid leukemia (AML), secondary AML, primary myelofibrosis, and others. RESULTS: Correlation between SF and SQUID was significant (r = 0.6; P < 0.001; log function). The chance of infection was increased 2.4-fold (95% CI 1.22-4.71) when SQUID values ranged >=1000 MUg Fe/g liver (P = 0.012). We found similar results for SF >1000 ng/mL (P = 0.003). A significant association between SQUID and fungal infection was also seen (P = 0.004). For patients with SQUID >=1000, the risk of proven fungal infection was increased 3.08-fold (95% CI 1.43-6.63). A similar association between SF >1000 and fungal infection was shown (P = 0.01). In univariate analysis, age was a prognostic factor for TRM (P = 0.034, HR 1.04, CI 1.00-1.08). SF >=1000 was associated with OS (P = 0.033, HR 2.09, CI 1.06 4.11) and EFS (P = 0.016, HR 2.15, 95% CI 1.15-4.10). In multivariate analysis on EFS, only age and SF >1000 remained as independent factors (HR 1.027, P = 0.040, 95% CI 1.001-1.054 and HR 2.058, P = 0.034, 95% CI 1.056-4.008, respectively). The multivariate analysis on TRM left age and SQUID values >=1000 in the final model (HR 1.045, P = 0.041, 95% CI 1.002-1.090 and HR 2.110, P = 0.103, 95% CI 0.859-5.183, respectively). CONCLUSION: Our data confirmed that SF >=1000 increases the risk of infection, moreover fungal infection in transplant recipients. As SQUID values correlate well with SF, we could show that SF is indeed a good surrogate parameter for iron overload when measured shortly before SCT. Prospective trials are needed to investigate the effect of iron chelation before or during SCT on transplant outcome. PMID- 26800434 TI - Increasing the Thermal Conductivity of Graphene-Polyamide-6,6 Nanocomposites by Surface-Grafted Polymer Chains: Calculation with Molecular Dynamics and Effective Medium Approximation. AB - By employing reverse nonequilibrium molecular dynamics simulations in a full atomistic resolution, the effect of surface-grafted chains on the thermal conductivity of graphene-polyamide-6.6 (PA) nanocomposites has been investigated. The interfacial thermal conductivity perpendicular to the graphene plane is proportional to the grafting density, while it first increases and then saturates with the grafting length. Meanwhile, the intrinsic in-plane thermal conductivity of graphene drops sharply as the grafting density increases. The maximum overall thermal conductivity of nanocomposites appears at an intermediate grafting density because of these two competing effects. The thermal conductivity of the composite parallel to the graphene plane increases with the grafting density and grafting length which is attributed to better interfacial coupling between graphene and PA. There exists an optimal balance between grafting density and grafting length to obtain the highest interfacial and parallel thermal conductivity. Two empirical formulas are suggested, which quantitatively account for the effects of grafting length and density on the interfacial and parallel thermal conductivity. Combined with effective medium approximation, for ungrafted graphene in random orientation, the model overestimates the thermal conductivity at low graphene volume fraction (f < 10%) compared with experiments, while it underestimates it at high graphene volume fraction (f > 10%). For unoriented grafted graphene, the model matches the experimental results well. In short, this work provides some valuable guides to obtain the nanocomposites with high thermal conductivity by grafting chain on the surface of graphene. PMID- 26800435 TI - Dupilumab: a revolutionary emerging drug in atopic dermatitis and its possible role in pemphigus. PMID- 26800437 TI - Termination Mechanism of the Radical Polymerization of Acrylates. AB - The termination mechanism of the radical polymerization of acrylates, namely the selectivity of disproportionation (Disp) and combination (Comb) between polymer end radicals, is unambiguously determined by the reaction of polyacrylate end radicals generated from corresponding "living" organotellurium omega-end polymer. While textbooks describe the occurrence of Comb, the reaction at 25 degrees C exclusively gives the Disp products. Ab initio molecular dynamics suggests that the products form by two pathways: The direct disproportionation reaction and a novel stepwise process that involves the initial formation of the C-O coupling product followed by intramolecular rearrangement. The termination at high temperature and low radical concentration increases the contribution of back biting reaction giving mid-chain radicals, and complex reaction pathways of the mid-chain radicals are clarified for the first time. PMID- 26800438 TI - The Organization of Controller Motifs Leading to Robust Plant Iron Homeostasis. AB - Iron is an essential element needed by all organisms for growth and development. Because iron becomes toxic at higher concentrations iron is under homeostatic control. Plants face also the problem that iron in the soil is tightly bound to oxygen and difficult to access. Plants have therefore developed special mechanisms for iron uptake and regulation. During the last years key components of plant iron regulation have been identified. How these components integrate and maintain robust iron homeostasis is presently not well understood. Here we use a computational approach to identify mechanisms for robust iron homeostasis in non graminaceous plants. In comparison with experimental results certain control arrangements can be eliminated, among them that iron homeostasis is solely based on an iron-dependent degradation of the transporter IRT1. Recent IRT1 overexpression experiments suggested that IRT1-degradation is iron-independent. This suggestion appears to be misleading. We show that iron signaling pathways under IRT1 overexpression conditions become saturated, leading to a breakdown in iron regulation and to the observed iron-independent degradation of IRT1. A model, which complies with experimental data places the regulation of cytosolic iron at the transcript level of the transcription factor FIT. Including the experimental observation that FIT induces inhibition of IRT1 turnover we found a significant improvement in the system's response time, suggesting a functional role for the FIT-mediated inhibition of IRT1 degradation. By combining iron uptake with storage and remobilization mechanisms a model is obtained which in a concerted manner integrates iron uptake, storage and remobilization. In agreement with experiments the model does not store iron during its high-affinity uptake. As an iron biofortification approach we discuss the possibility how iron can be accumulated even during high-affinity uptake. PMID- 26800439 TI - Predictive value of negative 3T multiparametric magnetic resonance imaging of the prostate on 12-core biopsy results. AB - OBJECTIVES: To evaluate the cancer detection rates for men undergoing 12-core systematic prostate biopsy with negative prebiopsy multiparametric magnetic resonance imaging (mpMRI) results. MATERIALS AND METHODS: Clinical data from consecutive men undergoing prostate biopsy who had undergone prebiopsy 3T mpMRI from December 2011 to August 2014 were reviewed from an institutional review board-approved prospective database. Men with negative prebiospy mpMRI results (negMRI) before biopsy were identified for the present analysis. Clinical features, cancer detection rates and negative predictive values were summarized. RESULTS: Seventy five men with negMRI underwent systematic 12-core biopsy during the study period. In the entire cohort, men with no previous biopsy, men with previously negative biopsy and men enrolled in active surveillance protocols, the overall cancer detection rates were 18.7, 13.8, 8.0 and 38.1%, respectively, and the detection rates for Gleason score (GS) >=7 cancer were 1.3, 0, 4.0 and 0%, respectively. The NPVs for all cancers were 81.3, 86.2, 92.0, and 61.9, and for GS >=7 cancer they were 98.7, 100, 96.0 and 100%, respectively. CONCLUSIONS: A negative prebiopsy mpMRI confers an overall NPV of 82% on 12-core biopsy for all cancer and 98% for GS >=7 cancer. Based on biopsy indication, these findings assist in prebiopsy risk stratification for detection of high-risk disease and may provide guidance in the decision to pursue biopsy. PMID- 26800440 TI - Isolation and Versatile Derivatization of an Unsaturated Anionic Silicon Cluster (Siliconoid). AB - The characteristic features of bulk silicon surfaces are echoed in the related partially substituted-and thus unsaturated-neutral silicon clusters (siliconoids). The incorporation of siliconoids into more-extended frameworks is promising owing to their unique electronic features, but further developments in this regard are limited by the notable absence of functionalized siliconoid derivatives until now. Herein we report the isolation and full characterization of the lithium salt of an anionic R5 Si6 -siliconoid, thus providing the missing link between silicon-based Zintl anions and siliconoid clusters. Proof-of principle for the high potential of this species for the efficient transfer of the intact unsaturated R5 Si6 moiety is demonstrated by clean reactions with representative electrophiles of Groups 13, 14, and 15. PMID- 26800441 TI - Cokeromyces recurvatus in a cervical papanicolaou test: A case report of a rare fungus with a brief review of the literature. AB - Here we report a rare case of Cokeromyces recurvatus in a Pap test in an asymptomatic pregnant patient. Each liquid-based Pap slide contained multiple rounded yeast-like forms measuring 10-30 um including some profiles with peripheral small buds. The background had neither epithelial abnormality nor any significant inflammation. A positive silver stain aided in confirming a fungal organism. Rare fungi were considered including Paracoccidioides brasiliensis due to the 'mariner's wheel' morphology of forms with peripheral budding; however, the final report morphologically favored C. recurvatus which was subsequently confirmed by culture. This is the sixth report of C. recurvatus isolated at a gynecologic site. While C. recurvatus has been reported to cause invasive disease in immunocompromised patients at deep sites, in the gynecologic tract it has so far been reported as a non-pathogenic colonizer. Awareness of this organism and use of either culture or molecular diagnostics are important in avoiding misdiagnosis. PMID- 26800442 TI - Phylogeography in Response to Reproductive Strategies and Ecogeographic Isolation in Ant Species on Madagascar: Genus Mystrium (Formicidae: Amblyoponinae). AB - The bulk of models used to understand the species diversification on Madagascar have been constructed using vertebrate taxa. It is not clear how these models affect less vagile species that may interact at a variety of spatial scales. Several studies on vertebrates have divided Madagascar into east-west bioclimatic regions, suggesting there is a fundamental division between eastern wet-adapted and western dry-adapted taxa. An alternative model of ecogeographic constraints shows a north-south division. We test whether the diversification in a small arthropod with variable degrees of dispersal conform to either model of ecogeographic constraints proposed for vertebrate taxa. We employ a molecular taxonomic dataset using ~2 kilobases nuDNA (Wg, LW Rh, Abd-A, 28s) and 790 basepairs mtDNA (CO1), along with geographic and habitat data, to examine the diversification patterns of the ant genus Mystrium Roger, 1862, (Subfamily Amblyoponinae) from Madagascar. The nuclear and mitochondrial phylogenies were both congruent with morphospecies as indicated in a recent revision of the genus. Species of Mystrium practice different colony reproductive strategies (winged queens vs non-winged queens). Alternate reproductive strategies led to inequalities in female dispersal ability among species, providing an additional layer for examination of the impacts of vagility on divergence, especially when measured using a maternally inherited locus. Mystrium species distribution patterns support these models of ecogeographic constraints. Reproductive strategy effected how Mystrium mtDNA lineages were associated with large-scale habitat distinctions and various topographical features. Furthermore, in some cases we find microgeographic population structure which appears to have been impacted by localized habitat differences (tsingy limestone formations, littoral forest) on a scale much smaller than that found in vertebrates. The current system offers a finer scale look at species diversification on the island, and helps achieve a more universal understanding of the generation of biodiversity on Madagascar. PMID- 26800444 TI - Effects of a Single Lyric Analysis Intervention on Withdrawal and Craving With Inpatients on a Detoxification Unit: A Cluster-Randomized Effectiveness Study. AB - BACKGROUND: For patients hospitalized on inpatient detoxification units, reducing negative symptoms such as withdrawal and craving is a key treatment area. Although lyric analysis is a commonly utilized music therapy intervention for clients in substance abuse rehabilitation, there is a lack of randomized controlled music therapy studies systematically investigating how lyric analysis interventions can affect patients on a detoxification unit. OBJECTIVE: The purpose of this cluster-randomized effectiveness study was to measure the effects of single-session group lyric analysis interventions on withdrawal and craving with patients on a detoxification unit. A secondary purpose of this study was to determine if relationships existed between treatment effects and participants' familiarity with the song. METHODS: Participants (N = 144) were cluster randomized to experimental (posttest only) or wait-list control (pretest only) conditions to provide treatment to all participants in an inclusive single session design. RESULTS: Although participants in the experimental condition had lower withdrawal and craving means than participants in the control condition, these differences were not significant. Familiarity of the song in the lyric analysis was not related to withdrawal or craving. CONCLUSION: Group-based lyric analysis interventions may be effective for temporarily relieving withdrawal and craving in patients on a detoxification unit. Familiarity of the song did not affect results. Implications for clinical practice, suggestions for future research, and limitations are provided. PMID- 26800445 TI - Analysis of Isoquinoline Alkaloid Composition and Wound-Induced Variation in Nelumbo Using HPLC-MS/MS. AB - Alkaloids are the most relevant bioactive components in lotus, a traditional herb in Asia, but little is known about their qualitative and quantitative distributions. Here, we report on the alkaloid composition in various lotus organs. Lotus laminae and embryos are rich in isoquinoline alkaloids, whereas petioles and rhizomes contain trace amounts of alkaloids. Wide variation of alkaloid accumulation in lamina and embryo was observed among screened genotypes. In laminae, alkaloid accumulation increases during early developmental stages, reaches the highest level at full size stage, and then decreases slightly during senescence. Vegetative and embryogenic tissues accumulate mainly aporphine-type and bisbenzylisoquinoline-type alkaloids, respectively. Bisbenzylisoquinoline type alkaloids may be synthesized mainly in lamina and then transported into embryo via latex through phloem translocation. In addition, mechanical wounding was shown to induce significant accumulation of specific alkaloids in lotus leaves. PMID- 26800443 TI - Impact of Organic Carbon Electron Donors on Microbial Community Development under Iron- and Sulfate-Reducing Conditions. AB - Although iron- and sulfate-reducing bacteria in subsurface environments have crucial roles in biogeochemical cycling of C, Fe, and S, how specific electron donors impact the compositional structure and activity of native iron- and/or sulfate-reducing communities is largely unknown. To understand this better, we created bicarbonate-buffered batch systems in duplicate with three different electron donors (acetate, lactate, or glucose) paired with ferrihydrite and sulfate as the electron acceptors and inoculated them with subsurface sediment as the microbial inoculum. Sulfate and ferrihydrite reduction occurred simultaneously and were faster with lactate than with acetate. 16S rRNA-based sequence analysis of the communities over time revealed that Desulfotomaculum was the major driver for sulfate reduction coupled with propionate oxidation in lactate-amended incubations. The reduction of sulfate resulted in sulfide production and subsequent abiotic reduction of ferrihydrite. In contrast, glucose promoted faster reduction of ferrihydrite, but without reduction of sulfate. Interestingly, the glucose-amended incubations led to two different biogeochemical trajectories among replicate bottles that resulted in distinct coloration (white and brown). The two outcomes in geochemical evolution might be due to the stochastic evolution of the microbial communities or subtle differences in the initial composition of the fermenting microbial community and its development via the use of different glucose fermentation pathways available within the community. Synchrotron-based x-ray analysis indicated that siderite and amorphous Fe(II) were formed in the replicate bottles with glucose, while ferrous sulfide and vivianite were formed with lactate or acetate. These data sets reveal that use of different C utilization pathways projects significant changes in microbial community composition over time that uniquely impact both the geochemistry and mineralogy of subsurface environments. PMID- 26800447 TI - The estrogen metabolites 2-methoxyestradiol and 2-hydroxyestradiol inhibit endometriotic cell proliferation in estrogen-receptor-independent manner. AB - Endometriosis, a painful disorder associated with infertility, is estimated to occur in approximately 7-10% of reproductive age women. Although endometriosis is considered as an estrogen-dependent disease, the role of estrogen metabolites via receptor-independent mechanisms has not yet been comprehensively clarified. In the present study, growth studies were performed comparing the effect of estradiol (E2), estrogen metabolites, that is, 2-hydroxyestradiol (2-OHE2) and 2 methoxyestradiol (2-ME), as well as estrogen-receptor-independent mechanisms using the estrogen receptor antagonist fulvestrant, on cell proliferation of endometriotic cells. The estrogen metabolites 2-OHE2 and 2-ME inhibited cell growth in a dose-dependent manner in pharmacological doses. Lower concentrations of 2-OHE2 had a stimulating effect on cell proliferation while pharmacologic doses exerted an antimitogenic effect. The effects on cell growth were at least partially receptor-independent, as demonstrated by simultaneous receptor antagonization with fulvestrant. In conclusion, our results demonstrate that in pharmacological doses the estrogen metabolites 2-ME and 2-OHE2 show inhibiting effects on the proliferation of endometriotic cells and may be promising substances for the treatment of endometriosis. PMID- 26800448 TI - A descriptive-comparative study of performance characteristics in futsal players of different levels. AB - Despite the increasing popularity of futsal, there is little information on performance characteristics of players. We aimed to determine the validity and reliability of a futsal shooting test and to evaluate and compare performance characteristics of three futsal playing levels. Twenty-four males (n = 8 elite, n = 8 semi-elite, n = 8 social) completed two trials to examine the reliability of the Massey Futsal Shooting Test (MFST) and to compare various fitness characteristics between groups. MFST time taken (P = 0.010), shot speed (P < 0.001) and points scored per shot (P < 0.001) were better for elite relative to social players. Test-retest reliability was acceptable for all groups, but it was most repeatable in elite players. Loughborough Soccer Passing Test performance was better in elite relative to social players (P = 0.004). There were no differences in countermovement-jump height between groups. Elite players ran faster over 5 m than both semi-elite (P = 0.043) and social (P = 0.002) and faster than the social players through 10 m (P = 0.028) and 20 m (P = 0.026). Distance covered in the Futsal Intermittent Endurance Test was higher in elite relative to semi-elite (P = 0.005) and social (P < 0.001) groups. The MFST is a valid and reliable protocol to assess futsal shooting-skill performance; elite players have superior shooting and passing skill and have greater sprinting and intermittent-running ability. PMID- 26800449 TI - A Well-Kept Treasure at Depth: Precious Red Coral Rediscovered in Atlantic Deep Coral Gardens (SW Portugal) after 300 Years. AB - BACKGROUND: The highly valuable red coral Corallium rubrum is listed in several Mediterranean Conventions for species protection and management since the 1980s. Yet, the lack of data about its Atlantic distribution has hindered its protection there. This culminated in the recent discovery of poaching activities harvesting tens of kg of coral per day from deep rocky reefs off SW Portugal. Red coral was irregularly exploited in Portugal between the 1200s and 1700s, until the fishery collapsed. Its occurrence has not been reported for the last 300 years. RESULTS: Here we provide the first description of an Atlantic red coral assemblage, recently rediscovered dwelling at 60-100 m depth in southern Portugal. We report a very slow growth rate (0.23 mm year-1), comparable to Mediterranean specimens. In comparison with most of the Mediterranean reports, the population reaches much larger sizes, estimated to be over one century old, and has a more complex coral branch architecture that promotes a rich assemblage of associated species, with boreal and Mediterranean affinities. Atlantic red coral is genetically distinct, yet mitochondrial analyses suggest that red corals from the Atlantic may have introgressed the Mediterranean ones after migration via the Algeria current. Our underwater surveys, using advanced mixed-gas diving, retrieved lost fishing gear in all coral sites. Besides illegal harvesting, the use and loss of fishing gears, particularly nets, by local fisheries are likely sources of direct impacts on these benthic assemblages. CONCLUSIONS: We extended the knowledge on the distribution of C. rubrum in the Atlantic, discovered its genetic distinctiveness, and reveal a rich deep-dwelling fauna associated to these coral assemblages. These findings support a barrier role of the Atlantic-Mediterranean transition zone, but reveal also hints of connectivity along its southern margin. The results highlight the genetic and demographic uniqueness of red coral populations from SW Iberia. However, we also report threats to these vulnerable populations by direct and indirect fishing activities and argue that its protection from any mechanically destructive activities is urgent as a precautionary approach. This study advances our understanding of phylogeographic barriers and range edge genetic diversity, and serves as a baseline against which to monitor future human and environmental disturbances to Atlantic C. rubrum. PMID- 26800452 TI - Women's Postpartum Sexual Health Program: A Collaborative and Integrated Approach to Restoring Sexual Health in the Postpartum Period. AB - The postpartum period presents unique challenges to couples' relationships and sexuality, yet these factors are often left unaddressed by health care providers. The Women's Postpartum Sexual Health Program (WPSHP), a four-session, group- and couples-based program delivered by an interdisciplinary care team at a family practice center, was designed specifically to address common concerns among postpartum women and their partners. The interrelated, biopsychosocial aspects of women's sexuality in the postpartum period are summarized, followed by a detailed description of the WPSHP content and structure. This information is intended to serve as a practical resource for implementation and adaptation of the WPSHP across different practice settings. PMID- 26800454 TI - The Separate Spheres Model of Gendered Inequality. AB - Research on role congruity theory and descriptive and prescriptive stereotypes has established that when men and women violate gender stereotypes by crossing spheres, with women pursuing career success and men contributing to domestic labor, they face backlash and economic penalties. Less is known, however, about the types of individuals who are most likely to engage in these forms of discrimination and the types of situations in which this is most likely to occur. We propose that psychological research will benefit from supplementing existing research approaches with an individual differences model of support for separate spheres for men and women. This model allows psychologists to examine individual differences in support for separate spheres as they interact with situational and contextual forces. The separate spheres ideology (SSI) has existed as a cultural idea for many years but has not been operationalized or modeled in social psychology. The Separate Spheres Model presents the SSI as a new psychological construct characterized by individual differences and a motivated system justifying function, operationalizes the ideology with a new scale measure, and models the ideology as a predictor of some important gendered outcomes in society. As a first step toward developing the Separate Spheres Model, we develop a new measure of individuals' endorsement of the SSI and demonstrate its reliability, convergent validity, and incremental predictive validity. We provide support for the novel hypotheses that the SSI predicts attitudes regarding workplace flexibility accommodations, income distribution within families between male and female partners, distribution of labor between work and family spheres, and discriminatory workplace behaviors. Finally, we provide experimental support for the hypothesis that the SSI is a motivated, system-justifying ideology. PMID- 26800455 TI - Correction: Oral Delivery of a Novel Recombinant Streptococcus mitis Vector Elicits Robust Vaccine Antigen-Specific Oral Mucosal and Systemic Antibody Responses and T Cell Tolerance. PMID- 26800456 TI - TTR kinetic stabilizers and TTR gene silencing: a new era in therapy for familial amyloidotic polyneuropathies. AB - INTRODUCTION: Transthyretin Familial Amyloid Polyneuropathy (TTR-FAP) is a rare disease with autosomal dominant transmission due to a point mutation of the TTR gene. By removing the main source of systemic mutant TTR, liver transplantation (LT) has become the reference therapy of this severe and fatal polyneuropathy of adult-onset, stopping disease progression in subgroup of patients. Recently, new therapeutic strategies have emerged, which intend to stabilize TTR or to silence the TTR gene. Amongst them, the TTR kinetic stabilizer tafamidis is the first drug approved in the EU. AREAS COVERED: We shall review the natural history of TTR-FAP and the best indications for LT. Data on the efficacy, safety and tolerability of the TTR kinetic stabilizers, tafamidis and diflunisal, have been reviewed, from the pivotal Phase III clinical trials published in PubMed medical journals or presented at international meetings. We will review the ongoing phase III clinical trials of TTR gene silencing with RNAi therapeutics and ASO published in clinicaltrialgov. EXPERT OPINION: Due to the data on efficacy, tolerability, safety, tafamidis and diflunisal became the first line anti-amyloid treatment in stage 1 TTR-FAP. Both drugs slow progression of the disease. Only tafamidis got marketing authorization. We are waiting for results of the 2 phase III clinical trials of TTR gene silencing in varied stages of the disease. PMID- 26800458 TI - Recommendations for benefit-risk assessment methodologies and visual representations. AB - PURPOSE: The purpose of this study is to draw on the practical experience from the PROTECT BR case studies and make recommendations regarding the application of a number of methodologies and visual representations for benefit-risk assessment. METHODS: Eight case studies based on the benefit-risk balance of real medicines were used to test various methodologies that had been identified from the literature as having potential applications in benefit-risk assessment. Recommendations were drawn up based on the results of the case studies. RESULTS: A general pathway through the case studies was evident, with various classes of methodologies having roles to play at different stages. Descriptive and quantitative frameworks were widely used throughout to structure problems, with other methods such as metrics, estimation techniques and elicitation techniques providing ways to incorporate technical or numerical data from various sources. Similarly, tree diagrams and effects tables were universally adopted, with other visualisations available to suit specific methodologies or tasks as required. Every assessment was found to follow five broad stages: (i) Planning, (ii) Evidence gathering and data preparation, (iii) Analysis, (iv) Exploration and (v) Conclusion and dissemination. CONCLUSIONS: Adopting formal, structured approaches to benefit-risk assessment was feasible in real-world problems and facilitated clear, transparent decision-making. Prior to this work, no extensive practical application and appraisal of methodologies had been conducted using real-world case examples, leaving users with limited knowledge of their usefulness in the real world. The practical guidance provided here takes us one step closer to a harmonised approach to benefit-risk assessment from multiple perspectives. PMID- 26800457 TI - The EFF-1A Cytoplasmic Domain Influences Hypodermal Cell Fusions in C. elegans But Is Not Dependent on 14-3-3 Proteins. AB - BACKGROUND: Regulatory and biophysical mechanisms of cell-cell fusion are largely unknown despite the fundamental requirement for fused cells in eukaryotic development. Only two cellular fusogens that are not of clear recent viral origin have been identified to date, both in nematodes. One of these, EFF-1, is necessary for most cell fusions in Caenorhabditis elegans. Unregulated EFF-1 expression causes lethality due to ectopic fusion between cells not developmentally programmed to fuse, highlighting the necessity of tight fusogen regulation for proper development. Identifying factors that regulate EFF-1 and its paralog AFF-1 could lead to discovery of molecular mechanisms that control cell fusion upstream of the action of a membrane fusogen. Bioinformatic analysis of the EFF-1A isoform's predicted cytoplasmic domain (endodomain) previously revealed two motifs that have high probabilities of interacting with 14-3-3 proteins when phosphorylated. Mutation of predicted phosphorylation sites within these motifs caused measurable loss of eff-1 gene function in cell fusion in vivo. Moreover, a human 14-3-3 isoform bound to EFF-1::GFP in vitro. We hypothesized that the two 14-3-3 proteins in C. elegans, PAR-5 and FTT-2, may regulate either localization or fusion-inducing activity of EFF-1. METHODOLOGY/PRINCIPAL FINDINGS: Timing of fusion events was slightly but significantly delayed in animals unable to produce full-length EFF-1A. Yet, mutagenesis and live imaging showed that phosphoserines in putative 14-3-3 binding sites are not essential for EFF-1::GFP accumulation at the membrane contact between fusion partner cells. Moreover, although the EFF-1A endodomain was required for normal rates of eff-1-dependent epidermal cell fusions, reduced levels of FTT-2 and PAR-5 did not visibly affect the function of wild-type EFF-1 in the hypodermis. CONCLUSIONS/SIGNIFICANCE: Deletion of the EFF-1A endodomain noticeably affects the timing of hypodermal cell fusions in vivo. However, prohibiting phosphorylation of candidate 14-3-3-binding sites does not impact localization of the fusogen. Hypodermal membrane fusion activity persists when 14 3-3 expression levels are reduced. PMID- 26800459 TI - Novel Genetic Resources in the Genus Vigna Unveiled from Gene Bank Accessions. AB - The genus Vigna (Fabaceae) consists of five subgenera, and includes more than 100 wild species. In Vigna, 10 crops have been domesticated from three subgenera, Vigna, Plectrotropis, and Ceratotropis. The habitats of wild Vigna species are so diverse that their genomes could harbor various genes responsible for environmental stress adaptation, which could lead to innovations in agriculture. Since some of the gene bank Vigna accessions were unidentified and they seemed to be novel genetic resources, these accessions were identified based on morphological traits. The phylogenetic positions were estimated based on the DNA sequences of nuclear rDNA-ITS and chloroplast atpB-rbcL spacer regions. Based on the results, the potential usefulness of the recently described species V. indica and V. sahyadriana, and some wild Vigna species, i.e., V. aconitifolia, V. dalzelliana, V. khandalensis, V. marina var. oblonga, and V. vexillata, was discussed. PMID- 26800461 TI - Urine Calcium and Bone Mineral Density in Calcium Stone-Forming Patients Treated with Alendronate and Hydrochlorothiazide. AB - INTRODUCTION: The objective was to evaluate the effect of hydrochlorothiazide and alendronate on urine calcium and bone mineral density in calcium stone-forming patients. MATERIAL AND METHODS: A prospective, non-randomized, non-observational comparative study was performed; this study included 111 patients with recurrent calcium stones, divided into 3 groups according to the treatment received. Group 1: 36 patients were treated with alendronate, 70 mg/week; Group 2: 34 patients were treated with alendronate, 70 mg/week + hydrochlorothiazide, 50 mg/day; Group 3: 41 patients were treated with hydrochlorothiazide, 50 mg/day. All patients received recommendations on diet and fluid intake. Other variables of bone mineral density were studied and analyzed, including bone remodeling markers and urinary calcium before and after 2 years of treatment. The statistical analysis was performed using the SPSS 17.0 program, with a statistical significance of p < 0.05. RESULTS: After 2 years of treatment, a significant difference was observed in the beta-crosslaps and a bone mineral density improvement in Group 1, along with a decrease in urinary calcium. In Group 3, a statistically significant difference was found in urinary calcium and fasting calcium/creatinine ratio, as well as an improvement in bone mineral density after 2 years of medical treatment. In Group 2 patients treated with the combination, there was an improvement in bone mineral density and a decrease in the beta-crosslaps marker similar to patients in Group 1, and a decrease in urinary calcium similar to those in Group 3. CONCLUSION: Combined alendronate + hydrochlorothiazide treatment offers the best results along with the improvement in bone mineral density and decrease in urine calcium in patients with recurrent calcium stones. PMID- 26800463 TI - Pembrolizumab for the treatment of non-small cell lung cancer. AB - INTRODUCTION: Immune checkpoint inhibitors targeting programmed death protein 1 (PD-1) receptor and its ligand, PD-L1, have recently led to significant and durable improvements in the clinical outcomes of some types of cancers including lung cancer. AREAS COVERED: Pembrolizumab was approved by the US FDA for the treatment of advanced or metastatic NSCLC whose disease has progressed after other treatments and with tumors that express PD-L1. In the phase I KEYNOTE-001 trial, the overall response rate (ORR) was 19.4%, the median progression-free survival (PFS) and overall survival (OS) were 3.7 months and 12.0 months for 495 unselected NSCLC patients. Strong PD-L1 expression (>= 50%) was associated with higher ORR, longer PFS, and longer OS. The phase II/III randomized KEYNOTE-010 trial demonstrated that pembrolizumab improved OS versus docetaxel in patients with previously treated NSCLC. EXPERT OPINION: Pembrolizumab, demonstrated durable response and prolonged OS especially in NSCLC patients with high expression of PD-1, thereby suggests a new treatment paradigm. However, many issues remain to be explored, including the identification of other robust biomarkers that can accurately predict the immune-responsiveness of tumors. Along with the identification of predictive biomarkers, further understanding of the tumor microenvironment is necessary to improve treatment outcomes through combinations of immunotherapy or combined with other targeted therapies. PMID- 26800462 TI - Single-Molecule Imaging of Individual Amyloid Protein Aggregates in Human Biofluids. AB - The misfolding and aggregation of proteins into amyloid fibrils characterizes many neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. We report here a method, termed SAVE (single aggregate visualization by enhancement) imaging, for the ultrasensitive detection of individual amyloid fibrils and oligomers using single-molecule fluorescence microscopy. We demonstrate that this method is able to detect the presence of amyloid aggregates of alpha-synuclein, tau, and amyloid-beta. In addition, we show that aggregates can also be identified in human cerebrospinal fluid (CSF). Significantly, we see a twofold increase in the average aggregate concentration in CSF from Parkinson's disease patients compared to age-matched controls. Taken together, we conclude that this method provides an opportunity to characterize the structural nature of amyloid aggregates in a key biofluid, and therefore has the potential to study disease progression in both animal models and humans to enhance our understanding of neurodegenerative disorders. PMID- 26800465 TI - Right-Side Paratracheal Lymph Node Dissection during Single-Incision Thoracoscopic Surgery Featuring Placement of a Bidirectional Retraction Suture. AB - In single-incision thoracoscopic surgery (SITS), multiple instruments are inserted through a single working window and at least three hands must move within the limited operative field. When lobectomy is required, SITS has not been preferred for right-side paratracheal lymph node dissection because of instrument collisions. We used our bidirectional traction suture technique to eliminate the need for an azygos vein retractor during dissection, and thereby overcame the instrument collision problem. PMID- 26800464 TI - Genetic Evidence for Genotoxic Effect of Entecavir, an Anti-Hepatitis B Virus Nucleotide Analog. AB - Nucleoside analogues (NAs) have been the most frequently used treatment option for chronic hepatitis B patients. However, they may have genotoxic potentials due to their interference with nucleic acid metabolism. Entecavir, a deoxyguanosine analog, is one of the most widely used oral antiviral NAs against hepatitis B virus. It has reported that entecavir gave positive responses in both genotoxicity and carcinogenicity assays. However the genotoxic mechanism of entecavir remains elusive. To evaluate the genotoxic mechanisms, we analyzed the effect of entecavir on a panel of chicken DT40 B-lymphocyte isogenic mutant cell line deficient in DNA repair and damage tolerance pathways. Our results showed that Parp1-/- mutant cells defective in single-strand break (SSB) repair were the most sensitive to entecavir. Brca1-/-, Ubc13-/- and translesion-DNA-synthesis deficient cells including Rad18-/- and Rev3-/- were hypersensitive to entecavir. XPA-/- mutant deficient in nucleotide excision repair was also slightly sensitive to entecavir. gamma-H2AX foci forming assay confirmed the existence of DNA damage by entecavir in Parp1-/-, Rad18-/- and Brca1-/- mutants. Karyotype assay further showed entecavir-induced chromosomal aberrations, especially the chromosome gaps in Parp1-/-, Brca1-/-, Rad18-/- and Rev3-/- cells when compared with wild-type cells. These genetic comprehensive studies clearly identified the genotoxic potentials of entecavir and suggested that SSB and postreplication repair pathways may suppress entecavir-induced genotoxicity. PMID- 26800466 TI - Human and primate-specific microRNAs in cancer: Evolution, and significance in comparison with more distantly-related research models: The great potential of evolutionary young microRNA in cancer research. AB - The largest proportion of microRNAs in humans (ca. 40-50%) originated in the phylogenetic grouping defined as primates. The dynamic evolution of this family of non-coding RNA is further demonstrated by the presence of microRNA unique to the human species. Investigations into the role of microRNA in cancer have until recently mainly focused on the more ancient members of this RNA family that are widely conserved in the animal kingdom. As I describe in this review the evolutionary young lineage and species-specific microRNA could be important contributors to cancers, especially in particular organs in primates compared to more distantly-related research models. Elucidating the biological significance of primate and human-specific microRNA in cancer could have important implications for cancer research and the use of non-primate animal models. PMID- 26800467 TI - [Epidemiologic data of hyperuricaemia prevalence in the conditions of primary care in Slovakia]. AB - Hyperuricaemia represents nowaday the new risk factor for cardiovascular diseases. Prevalence data and its treatment in our patient's population are still missing. Literature data shows, that its prevalence differs in various populations significantly from 4 % up to 40 % with race and geographical means. In the hospital population its prevalence is about 7 % and represents the important predictor of hospital mortality, e.i with heart failure. From the Framingham data relative risk was estimated of 25 % for cardiovascular diseases, coronary heart disease and all-course mortality. From the epidemiologic survey Mirror Slovakia hyperuricaemia was evaluated from the sample of 20 000 patients from the primare care physicians in order to see the picture on this newer risk factor. KEY WORDS: cardiovascular diseases - epidemiology - hyperuricaemia - therapy. PMID- 26800468 TI - [Management of treatment in patients with neuroendocrine neoplasmas of digestive tract]. AB - Neuroendocrine neoplasmas are a form of cancer arising from cells of diffuse neuroendocrine system. They produce peptides or amines that act as hormones or neurotransmitters. Incidence of NENs is relatively low. Diagnostic work-up and treatment requires a multidisciplinary team approach. The aim of this study was an analysis of data from patients with well-differentiated neuroendocrine neoplasmas of gastrointestinal tract. The study included patients followed up from 1998 to 2013 with histologically confirmed well-differentiated digestive neuroendocrine neoplasm with low or intermediate malignant potential. 97 patients were included; 34 men (35.1 %) and 63 women (64.9 %). In patients being diagnosed after 2005 interferon treatment is significantly less used than endoscopic and peptide receptor radionuclide therapy. We have identified more appropriate discriminant values of 5-HIAA and chromogranin A (6.8 mg/24 hours; 70 ng/ml) for predicting the presence of metastases at the time of diagnosis. We have identified following risk factors for overall mortality: liver metastases, presence of diarrhea, flush, small bowel primary tumor, high values of CgA and 5 HIAA at the time of diagnosis (5-HIAA > 520.52 mg/24 hours, CgA > 174.5 ng/ml). Surgical treatment was found to be a positive prognostic factor. KEY WORDS: chromogranin A - 5-hydroxyindoleacetic acid - neuroendocrine neoplasm. PMID- 26800469 TI - [Specifics of using ambulatory blood pressure monitoring in the elderly]. AB - Arterial hypertension is a chronic disease which represents a major risk factor for damage of cardiovascular system. Insufficient control of elevated blood pressure is associated with the development of target organ damage, in-creased cardiovascular morbidity and mortality with a adverse prognostic value. Using ambulatory blood pressure monitoring (ABPM) we can improve the overall management of elderly patients at which the prevalence of arterial hypertension is particularly high. KEY WORDS: ambulatory blood pressure monitoring (ABPM) - cardiometabolic risk factors - diurnal index - chronopharmacological aspects - management of arterial hypertension. PMID- 26800470 TI - [Arterial hypertension - multicirculus vitiosus vasorum]. AB - AIM: The aim of this review is to address documents and a number of studies on hypertension published in the last years in order to assess their contribution to our expanding knowledge of arterial hypertension. DISCUSSION: Arterial hypertension is not defined by symptoms and signs but by numbers of blood pressure values. Arterial hypertension is vascular disease (vascular risk factor) of many vascular diseases (atherosclerosis; arteriolosclerosis/arteriolonecrosis/arteriolocalcinosis; arterial thrombosis; arterial embolism; arterial thromboembolism; arterial dissection; complicated arterial aneurysm) and other. CONCLUSION: Arterial hypertension is cause and consequence of functional (endothelial dysfunction) and of structural organovascular injury (multiorganomultivascular disease). Blood vessels are culprits, implements and victims of arterial hypertension and of organovascular arterial diseases. KEY WORDS: angiology/vascular medicine - arterial hypertension - blood vessels - internal medicine - organovascular arterial diseases - vascular. PMID- 26800471 TI - [Hormonal changes in inflammatory bowel disease]. AB - Inflammatory bowel disease is often accompanied by extraintestinal manifestations due to a common autoimmune etiopathogenesis, chronic systemic inflammation, frequent nutrition deficits, and the treatment. Endocrine system changes belong to manifestations too. Interaction is mutual, Crohn's disease and ulcerative colitis cause functional and morphological changes of endocrine tissues. On the other hand the endocrine disorders negatively influence the course of bowel disease. In the article we analyze correlation of IBD with gonadal hormone production and fertility, with adrenal function, with the function and morphology of the thyroid, with growth hormone production and growth disorders in children, and with bone mineral density reduction. This topic is not studied enough and needs more analysis and clarification. KEY WORDS: Crohn's disease - endocrine system - inflammatory bowel disease - ulcerative colitis. PMID- 26800472 TI - [Diagnostics of polycystic ovary syndrome]. AB - Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy among women of reproductive age and the most frequent cause of menstruation cycle disorders. It is marked by a hyperandrogenic state (clinical and/or biochemical) and ovulatory dysfunction (anovulation and/or ultrasonographic finding of polycystic ovaries), which are also criteria for its diagnosis according to Androgen Excess and PCOS Society. The syndrome has multiple phenotypic expressions, among them besides the above characteristics also a metabolic syndrome, primarily obesity and insulin resistance. Diagnosing of PCOS may be rather exacting in clinical practice and it remains to be a diagnosis per exclusionem, following elimination of other causes of hyperandrogenic state and chronic oligo-anovulation. It requires a close cooperation between a gynecologist and endocrinologist and with regard to frequent metabolic complications also with an internist, diabetologist and possibly cardiologist. KEY WORDS: AES criteria - diagnosis - differential diagnosis - polycystic ovary syndrome. PMID- 26800473 TI - [Non usual cases of hypoglycaemia - hypoglycaemia factitia]. AB - Hypoglycaemia factitia means also in recent time serious diagnostic and therapeutic problem in medical clinical practice, whereby often repeating episodes of serious hypoglycaemia in patients with diabetes mellitus, but also in patients without diabetes mellitus could be very difficult do resolve. First unsuccessful diagnosis implicit from wrong chose of examination algorithm, can lead to unidentified surgical interventions as are laparotomy and pancreatectomy, respectively. Hypoglycaemia factitia is considered to be one of many manifestations of so called Munch-hausens syndrome for that is typical acting of diabetic patient with goal to intentionally making hypoglycaemia or within suicidal attempt of patient on the basis psychological disease with intention to attract attention of surrounding community to himself due to application of insulin or sulfonylurea drugs. Diagnostic and therapeutic process could be in the case of hypoglycaemia factitia extremely difficult as from time side, than from health and also from economical side and that why necessary to approach with maximum responsibility. KEY WORDS: diabetes mellitus - hypoglycaemia factitia - Munchhausens syndrome. PMID- 26800474 TI - [Is iron important in heart failure?]. AB - Iron deficiency is a frequent comorbidity in a patient with chronic heart failure, and it associates with a worse pro-gnosis of that patient. Mainly worse quality of life and more rehospitalizations are in these iron deficient patients. Iron metabolism is rather complex and there is some new information concerning this complexity in heart failure. We distinquish an absolute and a functional iron deficiency in heart failure. It is this deficit which is important and not as much is anemia important here. Prevalence of anaemia in heart failure is about 30-50 %, higher it is in patients suffering more frequently heart failure decompensations. Treatment of iron deficiency is important and it improves prognosis of these patients. Most experiences there are with i.v. iron treatment (FERRIC HF, FAIR HF and CONFIRM HF studies), less so with per oral treatment. There are no clinical trials which analysed mortality influences. KEY WORDS: heart failure - iron metabolism in heart failure - prevalence of iron deficit - treatment of iron deficiency in heart failure. PMID- 26800475 TI - [Novel diagnostic and therapeutic procedures in diabetic nephropathy]. AB - Epidemiological studies show increasing prevalence of diabetic nephropathy. Diabetic patients with chronic kidney disease are the biggest group from among patients on renal replacement therapy. Renal Pathology Society developed pathological classification of diabetic nephropathy. The cardinal biochemical diagnostic parameters are albuminuria and estimated glomerular filtration rate. European Renal Best Practice work group developed Clinical Practice Guideline on management of patients with diabetes and chronic kidney disease stage 3b or higher. KEY WORDS: epidemiology of diabetic nephropathy - diagnostics of diabetic nephropathy - therapy of chronic kidney disease in diabetic patients. PMID- 26800476 TI - [Are we to pay attention to factor XII deficiency?]. AB - Severe coagulation factor XII (FXII) deficiency is a very rare, mysterious and not well known inherited condition. Unlike other coagulation factor deficiencies, it is totally asymptomatic. Surprisingly, it does not lead to abnormal bleeding, even with major surgical procedures. The explanation for the lack of bleeding manifestations is unknown. It is suggested, but unproven, that patients are not sufficiently protected from thrombosis. FXII deficiency is usually discovered by accident through a routine coagulation testing done prior to surgery. Since FXII plays an important role in clot formation during in vitro measurements, its deficiency causes a marked prolongation of the activated partial thromboplastin time in the laboratory examination. The main concern related to FXII deficiency is the unnecessary testing, delay in health care and worry of surgical interventions that may be prompted by the abnormal laboratory result. KEY WORDS: activated partial thromboplastin time - bleeding - blood coagulation - factor XII. PMID- 26800477 TI - Uterine rupture in a setting of past tubal isthmus laparoscopic resection with successful maternal outcome and live birth: A case report. PMID- 26800478 TI - Influence of macromolecule baseline on 1 H MR spectroscopic imaging reproducibility. AB - PURPOSE: Poorly characterized macromolecular (MM) and baseline artefacts are known to reduce metabolite quantitation accuracy in 1 H MR spectroscopic imaging (MRSI). Increasing echo time (TE) and improvements in MM analysis schemes have both been proposed as strategies to improve metabolite measurement reliability. In this study, the influence of TE and two MM analysis schemes on MRSI reproducibility are investigated. METHODS: An experimentally acquired baseline was collected using an inversion recovery sequence (TI = 750 ms) and incorporated into the analysis method. Intrasubject reproducibility of MRSI scans, acquired at 3 Tesla, was assessed using metabolite coefficients of variance (COVs) for both experimentally acquired and simulated MM analysis schemes. In addition, the reproducibility of TE = 35 ms, 80 ms, and 144 ms was evaluated. RESULTS: TE = 80 ms was the most reproducible for singlet metabolites with COVs < 6% for total N acetyl-aspartate, total creatine, and total choline; however, moderate multiplet dephasing was observed. Analysis incorporating the experimental baseline achieved higher Glu and Glx reproducibility at TE = 35 ms, and showed improvements over the simulated baseline, with higher efficacy for poorer data. CONCLUSION: Overall, TE = 80 ms yielded the most reproducible singlet metabolite estimates. However, combined use of a short TE sequence and the experimental baseline may be preferred as a compromise between accuracy, multiplet dephasing, and T2 bias on metabolite estimates. Magn Reson Med 77:34-43, 2017. (c) 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. PMID- 26800479 TI - SAM-II Riboswitch Samples at least Two Conformations in Solution in the Absence of Ligand: Implications for Recognition. AB - Conformational equilibria are increasingly recognized as pivotal for biological function. Traditional structural analyses provide a static image of conformers in solution that sometimes present conflicting views. From (13) C and (1) H chemical exchange saturation transfer experiments, in concert with ligation and selective labeling strategies, we show that in the absence of metabolite, a Mg(2+) (0-0.5 mm)-bound apo SAM-II riboswitch RNA exists in a minor (~10 %) partially closed state that rapidly exchanges with a predominantly (~90 %) open form with a lifetime of ~32 ms. The base and sugar (H6,C6, H1',C1') chemical shifts of C43 for the dominant conformer are similar to those of a free CMP, but those of the minor apo species are comparable to shifts of CMPs in helical RNA regions. Our results suggest that these transient, low populated states stabilized by Mg(2+) will likely enhance rapid ligand recognition and, we anticipate, will play potentially ubiquitous roles in RNA signaling. PMID- 26800480 TI - Protein-fold recognition using an improved single-source K diverse shortest paths algorithm. AB - Protein structure prediction, when construed as a fold recognition problem, is one of the most important applications of similarity search in bioinformatics. A new protein-fold recognition method is reported which combines a single-source K diverse shortest path (SSKDSP) algorithm with Enrichment of Network Topological Similarity (ENTS) algorithm to search a graphic feature space generated using sequence similarity and structural similarity metrics. A modified, more efficient SSKDSP algorithm is developed to improve the performance of graph searching. The new implementation of the SSKDSP algorithm empirically requires 82% less memory and 61% less time than the current implementation, allowing for the analysis of larger, denser graphs. Furthermore, the statistical significance of fold ranking generated from SSKDSP is assessed using ENTS. The reported ENTS-SSKDSP algorithm outperforms original ENTS that uses random walk with restart for the graph search as well as other state-of-the-art protein structure prediction algorithms HHSearch and Sparks-X, as evaluated by a benchmark of 600 query proteins. The reported methods may easily be extended to other similarity search problems in bioinformatics and chemoinformatics. The SSKDSP software is available at http://compsci.hunter.cuny.edu/~leixie/sskdsp.html. PMID- 26800481 TI - Risk assessment to guide cervical screening strategies in a large Chinese population. AB - Three different cervical screening methods [cytology, human papillomavirus(HPV) testing and visual inspection with acetic acid(VIA)] are being considered in China for the national cervical screening program. Comparing risks of CIN3 and cervical cancer (CIN3+) for different results can inform test choice and management guidelines. We evaluated the immediate risk of CIN3+ for different screening results generated from individual and combined tests. We compared tests using a novel statistic designed for this purpose called Mean Risk Stratification (MRS), in a pooled analysis of 17 cross sectional population-based studies of 30,371 Chinese women screened with all 3 methods and diagnosed by colposcopically directed biopsies. The 3 tests combined powerfully distinguished CIN3+ risk; triple-negative screening conferred a risk of 0.01%, while HPV-positive HSIL+ that was VIA-positive yielded a risk of 57.8%. Among the three screening tests, HPV status most strongly stratified CIN3+ risk. Among HPV-positive women, cytology was the more useful second test. In HPV-negative women, the immediate risks of CIN3+ ranged from 0.01% (negative cytology), 0.00% (ASC-US), 1.1% (LSIL), to 6.6 (HSIL+). In HPV-positive women, the CIN3+ risks were 0.9% (negative cytology), 3.6% (ASC-US), 6.3% (LSIL) and 38.5% (HSIL+). VIA results did not meaningful stratify CIN3+ risk among HPV-negative women with negative or ASC-US cytology; however, positive VIA substantially elevated CIN3+ risk for all other, more positive combinations of HPV and cytology compared with a negative VIA. Because all 3 screening tests had independent value in defining risk of CIN3+, different combinations can be optimized as pragmatic strategies in different resource settings. PMID- 26800482 TI - Advancements of vertically aligned liquid crystal displays. AB - This review describes the recent advancements in the field of the vertical aligned (VA) liquid crystal displays. The process and formation of different vertical alignment modes such as conventional VA, patterned VA, multi-domain VA, and polymer stabilised VA etc are widely discussed. Vertical alignment of liquid crystal due to nano particle dispersion in LC host, bifunctional PR-SAM formed by silane coupling reaction to oxide surfaces, azo dye etc., are also highlighted and discussed. Overall, the article highlights the advances in the research of vertical aligned liquid crystal in terms of their scientific and technological aspects. PMID- 26800483 TI - Ghrelin-related peptides do not modulate vasodilator nitric oxide production or superoxide levels in mouse systemic arteries. AB - The ghrelin gene is expressed in the stomach where it ultimately encodes up to three peptides, namely, acylated ghrelin, des-acylated ghrelin and obestatin, which all have neuroendocrine roles. Recently, the authors' reported that these peptides have important physiological roles in positively regulating vasodilator nitric oxide (NO) production in the cerebral circulation, and may normally suppress superoxide production by the pro-oxidant enzyme, Nox2-NADPH oxidase. To date, the majority of studies using exogenous peptides infer that they may have similar roles in the systemic circulation. Therefore, this study examined whether exogenous and endogenous ghrelin-related peptides modulate NO production and superoxide levels in mouse mesenteric arteries and/or thoracic aorta. Using wire myography, it was found that application of exogenous acylated ghrelin, des acylated ghrelin or obestatin to mouse thoracic aorta or mesenteric arteries failed to elicit a vasorelaxation response, whereas all three peptides elicited vasorelaxation responses of rat thoracic aorta. Also, none of the peptides modulated mouse aortic superoxide levels as measured by L-012-enhanced chemiluminescence. Next, it was found that NO bioactivity and superoxide levels were unaffected in the thoracic aorta from ghrelin-deficient mice when compared with wild-type mice. Lastly, using novel GHSR-eGFP reporter mice in combination with double-labelled immunofluorescence, no evidence was found for the growth hormone secretagogue receptor (GHSR1a) in the throracic aorta, which is the only functional ghrelin receptor identified to date. Collectively these findings demonstrate that, in contrast to systemic vessels of other species (e.g. rat and human) and mouse cerebral vessels, ghrelin-related peptides do not modulate vasodilator NO production or superoxide levels in mouse systemic arteries. PMID- 26800485 TI - Broadening the imaging phenotype of dysferlinopathy at different disease stages. AB - INTRODUCTION: MRI characterization of dysferlinopathy has been mostly limited to the lower limbs. We aimed to broaden the MRI description of dysferlinopathy and to correlate it with objective measures of motor dysfunction. METHODS: Sequential whole-body axial MRI was performed in 27 patients with genetically confirmed dysferlinopathy classified according to disease duration. Spearman correlations of fatty infiltration scores versus Motor Function Measure (MFM) were calculated. RESULTS: Significant fatty infiltration was symmetrically present in early stages mainly in the posterior compartments of legs and thighs, thigh adductors, pelvic girdle, and some paravertebral muscles and the subscapularis. Later, fatty infiltration involved leg and thigh anterior compartments, arms and forearms, paravertebral, and trunk muscles. MRI infiltration score correlated positively with disease duration and negatively with MFM scale. CONCLUSIONS: We expand MRI characterization of dysferlinopathy and provide evidence for use of MRI scoring combined with motor functional scales to assess the natural course of disease. Muscle Nerve, 2016 Muscle Nerve 54: 203-210, 2016. PMID- 26800486 TI - A review of status of tetrabromobisphenol A (TBBPA) in China. AB - Tetrabromobisphenol A (TBBPA), a currently intensively used brominated flame retardant (BFR), is employed primarily as a reactive flame retardant in printed circuit boards but also has additive applications in several types of polymers. TBBPA is a ubiquitous environmental contaminant that is observed in both abiotic and biotic matrices. This paper summarizes and critically reviews the published scientific data concerning the current pollution status of TBBPA in China. To provide an indication of the seriousness of the pollution levels of TBBPA in China, the data are compared with available existing data from other countries of the world. According to the available data, the sources of TBBPA in China are mainly derived from the primitive e-waste dismantling, TBBPA manufacturing and processing of TBBPA-based materials. The most serious cases of TBBPA pollution in China are in Guiyu, Guangdong (primitive e-waste dismantling site) with concentrations of TBBPA reaching 66,010-95,040 pg m(-3) in air, Shouguang, Shandong (TBBPA manufacturing site) with concentrations of TBBPA reaching 1.64 7758 ng g(-1) dry weight in soil, and Chaohu Lake, Anhui (industry concentration site) with concentrations of TBBPA reaching 850-4870 ng L(-1) in water. In general, China is the most polluted region as affected by TBBPA compared with other countries. The present review preliminarily reveals the research status of TBBPA in China. PMID- 26800487 TI - Interactive effects of selected pharmaceutical mixtures on bioaccumulation and biochemical status in crucian carp (Carassius auratus). AB - The aim of this study was to evaluate the interactive effects of fluoxetine (FLU), roxithromycin (ROX) and propranolol (PRP) on the bioaccumulation and biochemical responses in the crucian carp Carassius auratus. After 7 days of binary exposure (ROX + FLU and PRP + FLU), the addition of waterborne FLU at nominal concentrations of 4, 20 and 100 MUg L(-1) significantly increased the accumulation of ROX and PRP in fish livers in most cases, although elevated ROX and PRP bioaccumulation levels were not observed in muscles or gills. The inductive response of 7-ethoxyresorufin O-deethylase (EROD) to PRP and that of 7 benzyloxy-4-trifluoromethyl-coumarin O-dibenzyloxylase (BFCOD) to ROX were inhibited by the co-administration of FLU at all tested concentrations. Correspondingly, marked inhibition of CYP1A and CYP3A mRNA expression levels was observed in the livers of fish co-treated with FLU + PRP and FLU + ROX relative to their PRP- and ROX-only counterparts, respectively. In addition, as reflected by superoxide dismutase (SOD) activity and malondialdehyde (MDA) content, co exposure to ROX + FLU and PRP + FLU seemed to induce stronger antioxidant responses than single pharmaceutical exposure in fish livers. This work indicated that the interactive effects of pharmaceutical mixtures could lead to perturbations in the bioaccumulation and biochemical responses in fish. PMID- 26800488 TI - Cetacean mass strandings and multidisciplinary work. PMID- 26800489 TI - Interactions between the antimicrobial agent triclosan and the bloom-forming cyanobacteria Microcystis aeruginosa. AB - Cyanobacteria can co-exist in eutrophic waters with chemicals or other substances derived from personal care products discharged in wastewater. In this work, we investigate the interactions between the antimicrobial agent triclosan (TCS) and the bloom-forming cyanobacteria Microcystis aeruginosa. M. aeruginosa was very sensitive to TCS with the 96h lowest observed effect concentration of 1.0 and 10MUg/L for inhibition of growth and photosynthetic activity, respectively. Exposure to TCS at environmentally relevant levels (0.1-2.0MUg/L) also affected the activities of superoxide dismutase (SOD) and the generation of reduced glutathione (GSH), while microcystin production was not affected. Transmission electron microscope (TEM) examination showed the destruction of M. aeruginosa cell ultrastructure during TCS exposure. TCS however, can be biotransformed by M. aeruginosa with methylation as a major biotransformation pathway. Furthermore, the presence of M. aeruginosa in solution promoted the photodegradation of TCS. Overall, our results demonstrate that M. aeruginosa plays an important role in the dissipation of TCS in aquatic environments but high residual TCS can exert toxic effects on M. aeruginosa. PMID- 26800491 TI - Juggling jobs: roles and mechanisms of multifunctional protease inhibitors in plants. AB - Multifunctional protease inhibitors juggle jobs by targeting different enzymes and thereby often controlling more than one biological process. Here, we discuss the biological functions, mechanisms and evolution of three types of multifunctional protease inhibitors in plants. The first type is double-headed inhibitors, which feature two inhibitory sites targeting proteases with different specificities (e.g. Bowman-Birk inhibitors) or even different hydrolases (e.g. alpha-amylase/protease inhibitors preventing both early germination and seed predation). The second type consists of multidomain inhibitors which evolved by intragenic duplication and are released by processing (e.g. multicystatins and potato inhibitor II, implicated in tuber dormancy and defence, respectively). The third type consists of promiscuous inhibitory folds which resemble mouse traps that can inhibit different proteases cleaving the bait they offer (e.g. serpins, regulating cell death, and alpha-macroglobulins). Understanding how multifunctional inhibitors juggle biological jobs increases our knowledge of the connections between the networks they regulate. These examples show that multifunctionality evolved independently from a remarkable diversity of molecular mechanisms that can be exploited for crop improvement and provide concepts for protein design. PMID- 26800490 TI - Chronic lymphocytic leukemia: Time to go past genomics? AB - Recent advances in massively parallel sequencing technologies have provided a detailed picture of the mutational landscape in CLL and underscored the vast degree of interpatient and intratumor heterogeneities. These studies have led to the characterization of novel putative driver genes and recurrently affected biological pathways, and to the modeling of CLL clonal evolution. We herein review selected aspects including recent advances in the biology of CLL and present cellular and biological processes involved in the development of CLL and potentially other mature B-cell lymphoproliferative neoplasms. PMID- 26800492 TI - Characterization of patients at high risk of melanoma in Austria. AB - BACKGROUND: Risk of melanoma is determined by genetic and exogenous factors. Only a few studies have included both characteristics in a comprehensive multivariable analysis. OBJECTIVES: To find determinants of patients at high risk of melanoma in Austria, including phenotype, genotype and lifestyle characteristics in comprehensive analyses. METHODS: In total, 1668 patients with melanoma from the M3 case-control study were studied. Overall, 567 participants were sequenced for CDKN2A, 232 for CDK4, 123 for MITF encoding the variant E318K and 964 for MC1R. RESULTS: Patients with melanoma with a positive family history (n = 190, 11.6%), multiple primary melanomas (n = 261, 15.7%) and younger age (< 50 years, n = 675, 40.5%) were defined as being at high risk. All other patients with melanoma were defined as the reference group. We found significant differences between those two groups and between the high-risk subgroups (positive family history, multiple primary melanomas and younger age). Pigmentation phenotype was associated with the high-risk group in general (childhood freckling, odds ratio 1.46, P = 0.007; blond/reddish hair colour, odds ratio 1.43, P = 0.011). Patients with a positive family history and patients with early-onset disease were similar regarding both their phenotypic characteristics and external factors. Established high-risk mutations in CDKN2A were found in cases with a positive family history (n = 12) or multiple melanomas (n = 2). Moreover, we found three patients carrying the MITF p.E318K variant, two with a CDK4 variant and seven with nonsynonymous MC1R variants with undescribed biological significance, of which four were predicted as damaging. CONCLUSIONS: Austrian patients could represent a reservoir for novel genetic variants. Further investigation of populations in Central and Eastern Europe might reveal more novel and disease-relevant variants. PMID- 26800493 TI - Spatio-temporal complexity of chimpanzee food: How cognitive adaptations can counteract the ephemeral nature of ripe fruit. AB - Ecological complexity has been proposed to play a crucial role in primate brain size evolution. However, detailed quantification of ecological complexity is still limited. Here we assess the spatio-temporal distribution of tropical fruits and young leaves, two primary chimpanzee (Pan troglodytes) foods, focusing on the predictability of their availability in individual trees. Using up to 20 years of information on monthly availability of young leaf, unripe and ripe fruit in plant species consumed by chimpanzees from tropical forests in East, Central, and West Africa, we estimated: (1) the forest-wide frequency of occurrence of each food type and (2) the predictability of finding ripe fruit-bearing trees, focusing on the timing, frequency, and amount of ripe fruit present. In all three forests, at least half of all encountered trees belonged to species that chimpanzees were known to feed on. However, the proportion of these trees bearing young leaves and fruit fluctuated widely between months. Ripe fruit was the most ephemeral food source, and trees that had more than half of their crown filled were at least nine times scarcer than other trees. In old growth forests only one large ripe fruit crop was on average encountered per 10 km. High levels of inter-individual variation in the number of months that fruit was present existed, and in some extreme cases individuals bore ripe fruit more than seven times as often as conspecifics. Some species showed substantially less variation in such ripe fruit production frequencies and fruit quantity than others. We hypothesize that chimpanzees employ a suite of cognitive mechanisms, including abilities to: (1) generalize or classify food trees; (2) remember the relative metrics of quantity and frequency of fruit production across years; and (3) flexibly plan return times to feeding trees to optimize high-energy food consumption in individual trees, and efficient travel between them. Am. J. Primatol. 78:626-645, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26800495 TI - Age at menarche is associated with the prevalence of non-alcoholic fatty liver disease later in life. AB - BACKGROUND: The aim of the present study was to investigate whether age at menarche is associated with non-alcoholic fatty liver disease (NAFLD) later in life. METHODS: The association between age at menarche and obesity, insulin resistance, and NAFLD after menopause was investigated in a cross-sectional study of 4128 postmenopausal Chinese women; NAFLD was diagnosed by hepatic ultrasound and information regarding age at menarche was collected using an interviewer administered questionnaire. RESULTS: Women with age at menarche <15 years had higher prevalence of overweight/obesity, insulin resistance, and NAFLD compared with women with age at menarche 15-18 or >18 years. Logistic regression revealed that women with earlier menarche had a higher risk for the age-adjusted prevalence of overweight/obesity, insulin resistance, and NAFLD, whereas later menarche showed a weaker, but still significant, association with a lower prevalence of NAFLD. However, further adjustment for some variables and current body mass index (BMI) or homeostasis model assessment of insulin resistance (HOMA IR) attenuated the association between later menarche and a lower prevalence of NAFLD. A decreasing trend in the risk of NAFLD was seen across increasing levels of age at menarche (age-adjusted Ptrend < 0.001; multivariate-adjusted Ptrend < 0.001; multivariate + current BMI-adjusted Ptrend = 0.03; multivariate + HOMA-IR adjusted Ptrend = 0.06). CONCLUSION: Age at menarche is associated with the prevalence of NAFLD later in life, independent of BMI and insulin resistance. PMID- 26800496 TI - Clinical Phenotype and Microvascular Dynamics of Subjects with Endothelial Dysfunction as Assessed by Peripheral Tonometry. AB - OBJECTIVE: To evaluate the characteristics and the determinants of ED, as measured by PAT. METHODS: We measured basal and post-ischemic digital pulse amplitude (EndoPAT((r))) in a mixed outpatient population of 206 diabetic and 101 non-diabetic subjects, of whom 50% with clinically manifest CVD, undergoing to an extensive clinical, biochemical, and vascular phenotype characterization. RESULTS: The major characteristics of ED (tertile 1 vs 3), in addition to lower post-ischemic vasodilatory reserve (34 vs 203%), were a 3-fold higher baseline pulse amplitude and a delayed (60 second) peak response. The main determinant of this response was the baseline pulse amplitude (Stbeta = -0.59), which in turn was influenced by age (Stbeta = 0.13), central obesity (Stbeta = 0.27) and inversely by HDL cholesterol (Stbeta = -0.17), and systolic blood pressure (Stbeta = -0.19). No association was observed with cardiovascular risk factors, previous cardiovascular event or extent of atherosclerosis (ABI and IMT, PWV). Most of the variability in baseline pulse amplitude remained unexplained (r(2) = 0.14). CONCLUSIONS: ED, as detected by PAT in a population enriched with subjects at risk for CVD neither reflects the burden of classical risk factors (under treatment) nor the severity of atherosclerosis. Aside from central obesity and HDL cholesterol, most of the factors responsible for this ED remain unknown. PMID- 26800494 TI - Genetic and epigenetic heterogeneity of epithelial ovarian cancer and the clinical implications for molecular targeted therapy. AB - Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy, and tumoural heterogeneity (TH) has been blamed for treatment failure. The genomic and epigenomic atlas of EOC varies significantly with tumour histotype, grade, stage, sensitivity to chemotherapy and prognosis. Rapidly accumulating knowledge about the genetic and epigenetic events that control TH in EOC has facilitated the development of molecular-targeted therapy. Poly (ADP-ribose) polymerase (PARP) inhibitors, designed to target homologous recombination, are poised to change how breast cancer susceptibility gene (BRCA)-related ovarian cancer is treated. Epigenetic treatment regimens being tested in clinical or preclinical studies could provide promising novel treatment approaches and hope for improving patient survival. PMID- 26800497 TI - Passiflora actinia hydroalcoholic extract and its major constituent, isovitexin, are neuroprotective against glutamate-induced cell damage in mice hippocampal slices. AB - OBJECTIVES: To investigate whether Passiflora actinia hydroalcoholic extract and its major constituent, isovitexin, protect mice hippocampal brain slices from glutamate-induced neurotoxicity. METHODS: Neuroprotective effect of the extract against glutamate-induced excitotoxicity (10 mm) was evaluated through cell viability of hippocampal slices. The extract or its flavonoids were directly applied to hippocampal slices and then subjected to glutamate-induced toxicity. Alternatively, hippocampal slices from extract-treated mice were also subjected to the same toxicity protocol. KEY FINDINGS: Mice supplementation with the extract protected hippocampal slices from in-vitro neurotoxicity. When directly applied to hippocampal slices, the extract showed a higher neuroprotective potential than a commercial dry extract of Passiflora incarnata, which was related to P. actinia extract which had higher isovitexin and total flavonoid content expressed as isovitexin. Isovitexin, but not apigenin, induced a similar neuroprotective response when applied alone, at a concentration equivalent to that found in the extract. CONCLUSIONS: This study highlights new neuropharmacological activity of the Passiflora genus, suggesting that it can act as modulator of the glutamatergic system. The search for improved pharmacotherapies with novel mechanisms of action has been shown of great importance for the treatment of resistant neurological and psychiatric disorders. PMID- 26800498 TI - Grapes (Vitis vinifera) as a Potential Candidate for the Therapy of the Metabolic Syndrome. AB - Metabolic syndrome is associated with several disorders, including hypertension, diabetes, hyperlipidemia as well as cardiovascular diseases and stroke. Plant derived polyphenols, compounds found in numerous plant species, play an important role as potential treatments for components of metabolic syndrome. Studies have provided evidence for protective effects of various polyphenol-rich foods against metabolic syndrome. Fruits, vegetables, cereals, nuts, and berries are rich in polyphenolic compounds. Grapes (Vitis vinifera), especially grape seeds, stand out as rich sources of polyphenol potent antioxidants and have been reported helpful for inhibiting the risk factors involved in the metabolic syndrome such as hyperlipidemia, hyperglycemia, and hypertension. There are also many studies about gastroprotective, hepatoprotective, and anti-obesity effects of grape polyphenolic compounds especially proanthocyanidins in the literature. The present study investigates the protective effects of grape seeds in metabolic syndrome. The results of this study show that grape polyphenols have significant effects on the level of blood glucose, lipid profile, blood pressure, as well as beneficial activities in liver and heart with various mechanisms. In addition, the pharmacokinetics of grape polyphenols is discussed. More detailed mechanistic investigations and phytochemical studies for finding the exact bioactive component(s) and molecular signaling pathways are suggested. PMID- 26800499 TI - Are registers the future for research in cerebral palsy? PMID- 26800500 TI - The Mexican Academy for Cerebral Palsy and Neurodevelopmental Disorders: new kid on the block. PMID- 26800501 TI - Inter-assessor variability: scant data proves the point. PMID- 26800502 TI - Relationship between built environment attributes and physical function in Japanese community-dwelling older adults. AB - AIM: To explore the relationships between the built environment and older adults' physical function. METHODS: The present cross-sectional study carried out in 2010 2012 used data drawn from 509 community-dwelling older adults aged 65-86 years living in Kasama City, a Japanese rural region. We evaluated physical function with the following performance tests: grip strength, sit-to-stand, timed up & go and walking speed. Using geographic information systems, we measured population density and the number of destinations related to daily life, community centers, medical facilities and recreational facilities within participants' neighborhoods. RESULTS: After adjusting for potential confounders, we found lower population density was related to poor performance of sit-to-stand and walking speed in both sexes, and grip strength in women (trend P < 0.05). A lower number of daily life-related destinations was related to poor performance of sit-to stand and walking speed in men, and grip strength and sit-to-stand in women. Similarly, the number of community centers was related to walking speed in both sexes. The number of medical and recreational facilities was also related to some physical performance in both sexes. A lower land use mix score, calculated by principal component analysis, was related to lower performance of sit-to-stand and walking speed in men, and grip strength and sit-to-stand in women. CONCLUSION: The present study suggests that, although there are some sex differences, low population density, land use mix, and fewer daily life-related destinations, community centers, medical facilities and recreational facilities are negative determinants of physical function. Geriatr Gerontol Int 2017; 17: 382-390. PMID- 26800503 TI - Spatial Metrics of Tumour Vascular Organisation Predict Radiation Efficacy in a Computational Model. AB - Intratumoural heterogeneity is known to contribute to poor therapeutic response. Variations in oxygen tension in particular have been correlated with changes in radiation response in vitro and at the clinical scale with overall survival. Heterogeneity at the microscopic scale in tumour blood vessel architecture has been described, and is one source of the underlying variations in oxygen tension. We seek to determine whether histologic scale measures of the erratic distribution of blood vessels within a tumour can be used to predict differing radiation response. Using a two-dimensional hybrid cellular automaton model of tumour growth, we evaluate the effect of vessel distribution on cell survival outcomes of simulated radiation therapy. Using the standard equations for the oxygen enhancement ratio for cell survival probability under differing oxygen tensions, we calculate average radiation effect over a range of different vessel densities and organisations. We go on to quantify the vessel distribution heterogeneity and measure spatial organization using Ripley's L function, a measure designed to detect deviations from complete spatial randomness. We find that under differing regimes of vessel density the correlation coefficient between the measure of spatial organization and radiation effect changes sign. This provides not only a useful way to understand the differences seen in radiation effect for tissues based on vessel architecture, but also an alternate explanation for the vessel normalization hypothesis. PMID- 26800504 TI - ADAM23 is downregulated in side population and suppresses lung metastasis of lung carcinoma cells. AB - Cancer cells contain a small population of cancer stem cells or cancer initiating cells, which can be enriched in the side population (SP) after fluorescence activated cell sorting. To examine the members of the ADAM, ADAMTS and MMP gene families related to phenotypes of the SP and the main population (MP), we screened the expression of all the members in the propagated SP and MP of A549 lung adenocarcinoma cells, and found that the relative expression ratio of ADAM23 in the MP to the SP is most highly increased, but none of them are increased in the SP. A similar result on the ADAM23 expression was obtained with another cell line, Calu-3 cells. Overexpression of ADAM23 inhibited colony formation, cell adhesion and migration, and knockdown of ADAM23 by shRNA showed the reverse effects. ADAM23-mediated suppression of colony formation, cell adhesion and migration was greatly reduced by treatment with neutralizing anti-ADAM23 antibody, anti-alphavbeta3 integrin antibody and/or ADAM23 disintegrin peptide. Expression of cancer stem cell-related genes, including AKRC1/2, TM4SF1 and NR0B1, was increased by knockdown of ADAM23. In addition, lung metastasis of A549 transfectants with different levels of ADAM23 expression was negatively regulated by the ADAM23 expression levels. Our data provide evidence that ADAM23 plays a role in suppression of cancer cell progression through interaction with alphavbeta3 integrin, and suggest that downregulation of ADAM23 in SP cells may contribute toward providing a cancer stem cell phenotype by facilitating the activity of integrin alphavbeta3. PMID- 26800505 TI - MiR-125a Rs12976445 Polymorphism is Associated with the Apoptosis Status of Nucleus Pulposus Cells and the Risk of Intervertebral Disc Degeneration. AB - BACKGROUND: Spinal degenerative diseases are a major health problem and social burden worldwide. Intervertebral disc degeneration (IDD) is the pathological basis of spinal degenerative diseases and is characterized by loss of nucleus pulposus cells due to excessive apoptosis caused by various factors. MicroRNAs (miRNAs) have been reported to be functionally involved in the control of apoptosis. METHODS: computational analysis and luciferase assay were used to identify the target of miR-125a, and cell culture, transfection were used to confirm such relationship. Sequencing was used to determine the genotype of each participant. RESULTS: We confirmed the previous report that the presence of the minor allele (T) of rs12976445 polymorphism significantly downregulated the expression level of miR-125a in nucleus pulposus cells, leading to less efficient inhibition of its target gene. We also validated TP53INP1 as a target of miR-125a in nucleus pulposus cells using a dual luciferase reporter system, and the transfection of miR-125a significantly reduced the expression of TP53INP1. The expression level of TP53INP1 was significantly lower in nucleus pulposus cells genotyped as CT or TT than in those genotyped as CC, and the apoptosis rate was consistently lower in the CC group than in the nucleus pulposus cells collected from individuals carrying at least one minor allele of rs12976445 polymorphism. To study the association between rs12976445 polymorphism and the risk of IDD, we enrolled 242 patients diagnosed with IDD and 278 normal controls, and significant differences were noted regarding the genotype distribution of rs12976445 between the IDD and the control groups (OR = 2.69, 95% C.I. = 1.88-3.83, p < 0.0001). In summary, rs12976445 polymorphism is significantly associated with the risk of IDD in the Chinese population. CONCLUSION: The present study indicated that miR-125a is a promising potential target for patients with IDD in clinical practice. PMID- 26800507 TI - Synthesis of molecularly imprinted photocatalysts containing low TiO2 loading: Evaluation for the degradation of pharmaceuticals. AB - A molecularly imprinted (MI) photocatalyst containing a low TiO2 loading (7.00 16.60mgL(-1) of TiO2) was prepared via an acid-catalyzed sol-gel route using different classes of pharmaceutical compounds (i.e., Atorvastatin, Diclofenac, Ibuprofen, Tioconazole, Valsartan, Ketoconazole and Gentamicine) as the template. Herein, our main goal was to test the hypothesis that photocatalysts based on molecular imprinting may improve the degradation performance of pharmaceutical compounds compared to that of a commercial sample (Degussa P25) due to presence of specific cavities in the silica domain. To elucidate certain trends between the performance of photocatalysts and their structural and textural properties, as well the effect of the structure of the drugs on molecular imprinting, the data were analyzed in terms of pore diameter, pore volume, surface area, zeta potential and six-membered ring percentage of silica. In comparison to the commercial sample (P25), we have shown that adsorption and degradation were enhanced from 48 to 752% and from 5 to 427%, respectively. A comparison with the control system (non-imprinted) indicates that the increased performance of the MI systems was due to the presence of specific cavities on the silica domain, and the textural and structural aspects also support this conclusion. The MI photocatalyst was reusable for seven cycles of reuse in which approximately 60% of its photocatalytic efficiency was preserved for the system containing Diclofenac as the template. PMID- 26800506 TI - Techniques for studying protein trafficking and molecular motors in neurons. AB - This review focused on techniques that facilitated the visualization of protein trafficking. In the mid-1990s the cloning of GFP allowed fluorescently tagged proteins to be expressed in cells and then visualized in real time. This advance allowed a glimpse, for the first time, of the complex system within cells for distributing proteins. It quickly became apparent, however, that time-lapse sequences of exogenously expressed GFP-labeled proteins can be difficult to interpret. Reasons for this include the relatively low signal that comes from moving proteins and high background rates from stationary proteins and other sources, as well as the difficulty of identifying the origins and destinations of specific vesicular carriers. In this review a range of techniques that have overcome these issues to varying degrees was reviewed and the insights into protein trafficking that they have enabled were discussed. Concentration will be on neurons, as they are highly polarized and, thus, their trafficking systems tend to be accessible for study. (c) 2016 Wiley Periodicals, Inc. PMID- 26800509 TI - Enteric-coated mycophenolate sodium: a new option for GHVD prophylaxis? PMID- 26800510 TI - Topical propranolol for a chronic recalcitrant wound. PMID- 26800511 TI - High Glass Transition Temperature Renewable Polymers via Biginelli Multicomponent Polymerization. AB - A novel and straightforward one-pot multicomponent polycondensation method was established in this work. The Biginelli reaction is a versatile multicomponent reaction of an aldehyde, a beta-ketoester (acetoacetate) and urea, which can all be obtained from renewable resources, yielding diversely substituted 3,4 dihydropyrimidin-2(1H)-ones (DHMPs). In this study, renewable diacetoacetate monomers with different spacer chain lengths (C3, C6, C10, C20) were prepared via simple transesterification of renewable diols and commercial acetoacetates. The diacetoacetate monomers were then reacted with renewable dialdehydes, i.e., terephthalaldehyde and divanillin in a Biginelli type step-growth polymerization. The obtained DHMP polymers (polyDHMPs) displayed high molar masses, high glass transition temperatures (Tg) up to 203 degrees C and good thermal stability (Td5%) of 280 degrees C. The Tg of the polyDHMPs could be tuned by variation of the structure of the dialdehyde or the diacetoacetate component. PMID- 26800512 TI - The effects of sex hormones on immune function: a meta-analysis. AB - The effects of sex hormones on immune function have received much attention, especially following the proposal of the immunocompetence handicap hypothesis. Many studies, both experimental and correlational, have been conducted to test the relationship between immune function and the sex hormones testosterone in males and oestrogen in females. However, the results are mixed. We conducted four cross-species meta-analyses to investigate the relationship between sex hormones and immune function: (i) the effect of testosterone manipulation on immune function in males, (ii) the correlation between circulating testosterone level and immune function in males, (iii) the effect of oestrogen manipulation on immune function in females, and (iv) the correlation between circulating oestrogen level and immune function in females. The results from the experimental studies showed that testosterone had a medium-sized immunosuppressive effect on immune function. The effect of oestrogen, on the other hand, depended on the immune measure used. Oestrogen suppressed cell-mediated immune function while reducing parasite loads. The overall correlation (meta-analytic relationship) between circulating sex hormone level and immune function was not statistically significant for either testosterone or oestrogen despite the power of meta analysis. These results suggest that correlational studies have limited value for testing the effects of sex hormones on immune function. We found little evidence of publication bias in the four data sets using indirect tests. There was a weak and positive relationship between year of publication and effect size for experimental studies of testosterone that became non-significant after we controlled for castration and immune measure, suggesting that the temporal trend was due to changes in these moderators over time. Graphical analyses suggest that the temporal trend was due to an increased use of cytokine measures across time. We found substantial heterogeneity in effect sizes, except in correlational studies of testosterone, even after we accounted for the relevant random and fixed factors. In conclusion, our results provide good evidence that testosterone suppresses immune function and that the effect of oestrogen varies depending on the immune measure used. PMID- 26800513 TI - Noninvasive Staging of Kidney Dysfunction Enabled by Renal-Clearable Luminescent Gold Nanoparticles. AB - As a "silent killer", kidney disease is often hardly detected at an early stage but can cause lethal kidney failure later on. Thus, a preclinical imaging technique that can readily differentiate between the stages of kidney dysfunction is highly desired for improving our fundamental understanding of kidney disease progression. Herein, we report that in vivo fluorescence imaging, enabled by renal-clearable near-infrared-emitting gold nanoparticles, can noninvasively detect kidney dysfunction, report on the dysfunctional stages, and even reveal adaptive function in a mouse model of unilateral obstructive nephropathy, which cannot be diagnosed with routine kidney function markers. These results demonstrate that low-cost fluorescence kidney functional imaging is highly sensitive and useful for the longitudinal, noninvasive monitoring of kidney dysfunction progression in preclinical research. PMID- 26800514 TI - HER 2 immunohistochemistry for breast cancer cell blocks can be used in the same way as that used for histological specimens. AB - BACKGROUND: Human epidermal growth factor receptor 2 (HER2) testing of samples from recurrent or metastatic breast cancer is recommended by the 2013 update of the American Society of Clinical Oncology/College of American Pathologists guidelines. Although cytological analysis can be applied to several types of metastatic lesions, the practical method for HER2 testing of cytological specimens is yet to be resolved. We conducted immunohistochemical (IHC) staining for HER2 in breast cancer cell blocks (CBs) and compared the results with those from the corresponding histological specimens. In cases of discrepancy between the two types of specimen, the bright-field HER2 dual in situ hybridization (DISH) assay was performed. METHODS: CBs were prepared from 54 surgically excised breast cancers. The cells were fixed in 10% buffered formalin and embedded in paraffin. A Ventana BenchMark ULTRA (Roche Diagnostics) with anti-HER-2/neu (4B5) rabbit monoclonal primary antibody and INFORM HER2/neu Dual ISH DNA Probe Cocktail was used for the assays. RESULTS: Successful results were obtained in 52 of 54 CBs. Forty cases showed agreement between CBs and the histological specimens. No discrepancy was observed between the two types of specimens in cases where HER2 expression was positive. IHC results of CB in 12 discrepant cases were HER2 intermediate or negative. The DISH results of 11 of these cases were negative. CONCLUSION: IHC staining of HER2 for breast cancer CBs can be used in the same way as that used for histological specimens, although the number of equivocal cases in CBs is greater than that in histological specimens. Diagn. Cytopathol. 2016;44:274-279. (c) 2016 The Authors Diagnostic Cytopathology Published by Wiley Periodicals, Inc. PMID- 26800515 TI - Identification and Comparison of Candidate Olfactory Genes in the Olfactory and Non-Olfactory Organs of Elm Pest Ambrostoma quadriimpressum (Coleoptera: Chrysomelidae) Based on Transcriptome Analysis. AB - The leaf beetle Ambrostoma quadriimpressum (Coleoptera: Chrysomelidae) is a predominant forest pest that causes substantial damage to the lumber industry and city management. However, no effective and environmentally friendly chemical method has been discovered to control this pest. Until recently, the molecular basis of the olfactory system in A. quadriimpressum was completely unknown. In this study, antennae and leg transcriptomes were analyzed and compared using deep sequencing data to identify the olfactory genes in A. quadriimpressum. Moreover, the expression profiles of both male and female candidate olfactory genes were analyzed and validated by bioinformatics, motif analysis, homology analysis, semi quantitative RT-PCR and RT-qPCR experiments in antennal and non-olfactory organs to explore the candidate olfactory genes that might play key roles in the life cycle of A. quadriimpressum. As a result, approximately 102.9 million and 97.3 million clean reads were obtained from the libraries created from the antennas and legs, respectively. Annotation led to 34344 Unigenes, which were matched to known proteins. Annotation data revealed that the number of genes in antenna with binding functions and receptor activity was greater than that of legs. Furthermore, many pathway genes were differentially expressed in the two organs. Sixteen candidate odorant binding proteins (OBPs), 10 chemosensory proteins (CSPs), 34 odorant receptors (ORs), 20 inotropic receptors [1] and 2 sensory neuron membrane proteins (SNMPs) and their isoforms were identified. Additionally, 15 OBPs, 9 CSPs, 18 ORs, 6 IRs and 2 SNMPs were predicted to be complete ORFs. Using RT-PCR, RT-qPCR and homology analysis, AquaOBP1/2/4/7/C1/C6, AquaCSP3/9, AquaOR8/9/10/14/15/18/20/26/29/33, AquaIR8a/13/25a showed olfactory specific expression, indicating that these genes might play a key role in olfaction-related behaviors in A. quadriimpressum such as foraging and seeking. AquaOBP4/C5, AquaOBP4/C5, AquaCSP7/9/10, AquaOR17/24/32 and AquaIR4 were highly expressed in the antenna of males, suggesting that these genes were related to sex-specific behaviors, and expression trends that were male specific were observed for most candidate olfactory genes, which supported the existence of a female-produced sex pheromone in A. quadriimpressum. All of these results could provide valuable information and guidance for future functional studies on these genes and provide better molecular knowledge regarding the olfactory system in A. quadriimpressum. PMID- 26800516 TI - Extensive Chromosomal Reorganization in the Evolution of New World Muroid Rodents (Cricetidae, Sigmodontinae): Searching for Ancestral Phylogenetic Traits. AB - Sigmodontinae rodents show great diversity and complexity in morphology and ecology. This diversity is accompanied by extensive chromosome variation challenging attempts to reconstruct their ancestral genome. The species Hylaeamys megacephalus--HME (Oryzomyini, 2n = 54), Necromys lasiurus--NLA (Akodontini, 2n = 34) and Akodon sp.--ASP (Akodontini, 2n = 10) have extreme diploid numbers that make it difficult to understand the rearrangements that are responsible for such differences. In this study we analyzed these changes using whole chromosome probes of HME in cross-species painting of NLA and ASP to construct chromosome homology maps that reveal the rearrangements between species. We include data from the literature for other Sigmodontinae previously studied with probes from HME and Mus musculus (MMU) probes. We also use the HME probes on MMU chromosomes for the comparative analysis of NLA with other species already mapped by MMU probes. Our results show that NLA and ASP have highly rearranged karyotypes when compared to HME. Eleven HME syntenic blocks are shared among the species studied here. Four syntenies may be ancestral to Akodontini (HME2/18, 3/25, 18/25 and 4/11/16) and eight to Sigmodontinae (HME26, 1/12, 6/21, 7/9, 5/17, 11/16, 20/13 and 19/14/19). Using MMU data we identified six associations shared among rodents from seven subfamilies, where MMU3/18 and MMU8/13 are phylogenetic signatures of Sigmodontinae. We suggest that the associations MMU2entire, MMU6proximal/12entire, MMU3/18, MMU8/13, MMU1/17, MMU10/17, MMU12/17, MMU5/16, MMU5/6 and MMU7/19 are part of the ancestral Sigmodontinae genome. PMID- 26800518 TI - Porosity in metal-organic framework glasses. AB - The porosity of a glass formed by melt-quenching a metal-organic framework, has been characterized by positron annihilation lifetime spectroscopy. The results reveal porosity intermediate between the related open and dense crystalline frameworks ZIF-4 and ZIF-zni. A structural model for the glass was constructed using an amorphous polymerization algorithm, providing additional insight into the gas-inaccessible nature of porosity and the possible applications of hybrid glasses. PMID- 26800517 TI - Innovation in Evaluating the Impact of Integrated Service-Delivery: The Integra Indexes of HIV and Reproductive Health Integration. AB - BACKGROUND: The body of knowledge on evaluating complex interventions for integrated healthcare lacks both common definitions of 'integrated service delivery' and standard measures of impact. Using multiple data sources in combination with statistical modelling the aim of this study is to develop a measure of HIV-reproductive health (HIV-RH) service integration that can be used to assess the degree of service integration, and the degree to which integration may have health benefits to clients, or reduce service costs. METHODS AND FINDINGS: Data were drawn from the Integra Initiative's client flow (8,263 clients in Swaziland and 25,539 in Kenya) and costing tools implemented between 2008-2012 in 40 clinics providing RH services in Kenya and Swaziland. We used latent variable measurement models to derive dimensions of HIV-RH integration using these data, which quantified the extent and type of integration between HIV and RH services in Kenya and Swaziland. The modelling produced two clear and uncorrelated dimensions of integration at facility level leading to the development of two sub-indexes: a Structural Integration Index (integrated physical and human resource infrastructure) and a Functional Integration Index (integrated delivery of services to clients). The findings highlight the importance of multi-dimensional assessments of integration, suggesting that structural integration is not sufficient to achieve the integrated delivery of care to clients--i.e. "functional integration". CONCLUSIONS: These Indexes are an important methodological contribution for evaluating complex multi-service interventions. They help address the need to broaden traditional evaluations of integrated HIV-RH care through the incorporation of a functional integration measure, to avoid misleading conclusions on its 'impact' on health outcomes. This is particularly important for decision-makers seeking to promote integration in resource constrained environments. PMID- 26800520 TI - Electrocatalytic reduction of CO2 by thiophene-substituted rhenium(i) complexes and by their polymerized films. AB - Three novel thiophene substituted bipyridine ligands and their corresponding rhenium complexes were synthesized and tested for the electrocatalytic reduction of CO2. Two complexes underwent oxidative electropolymerization on a glassy carbon electrode (GCE) surface. The conductive polymers chemically deposited on the GCE allow electron transport from the surface to the polymer-attached rhenium catalytic center in contact with the solution. The chemically modified electrodes show significant catalytic activities for CO2 reduction, and moderate relative higher stabilities when compared with the homogeneous solution counterparts. PMID- 26800519 TI - Expression of the Long Non-Coding RNA HOTAIR Correlates with Disease Progression in Bladder Cancer and Is Contained in Bladder Cancer Patient Urinary Exosomes. AB - Exosomes are 30-150nM membrane-bound secreted vesicles that are readily isolated from biological fluids such as urine (UEs). Exosomes contain proteins, micro RNA (miRNA), messenger RNA (mRNA), and long non-coding RNA (lncRNA) from their cells of origin. Although miRNA, protein and lncRNA have been isolated from serum as potential biomarkers for benign and malignant disease, it is unknown if lncRNAs in UEs from urothelial bladder cancer (UBC) patients can serve as biomarkers. lncRNAs are > 200 nucleotide long transcripts that do not encode protein and play critical roles in tumor biology. As the number of recognized tumor-associated lncRNAs continues to increase, there is a parallel need to include lncRNAs into biomarker discovery and therapeutic target algorithms. The lncRNA HOX transcript antisense RNA (HOTAIR) has been shown to facilitate tumor initiation and progression and is associated with poor prognosis in several cancers. The importance of HOTAIR in cancer biology has sparked interest in using HOTAIR as a biomarker and potential therapeutic target. Here we show HOTAIR and several tumor associated lncRNAs are enriched in UEs from UBC patients with high-grade muscle invasive disease (HGMI pT2-pT4). Knockdown of HOTAIR in UBC cell lines reduces in vitro migration and invasion. Importantly, loss of HOTAIR expression in UBC cell lines alters expression of epithelial-to-mesenchyme transition (EMT) genes including SNAI1, TWIST1, ZEB1, ZO1, MMP1 LAMB3, and LAMC2. Finally, we used RNA sequencing to identify four additional lncRNAs enriched in UBC patient UEs. These data, suggest that UE-derived lncRNA may potentially serve as biomarkers and therapeutic targets. PMID- 26800521 TI - Spectral Sensitivity Measured with Electroretinogram Using a Constant Response Method. AB - A new method is presented to determine the retinal spectral sensitivity function S(lambda) using the electroretinogram (ERG). S(lambda)s were assessed in three different species of myomorph rodents, Gerbils (Meriones unguiculatus), Wistar rats (Ratus norvegicus), and mice (Mus musculus). The method, called AC Constant Method, is based on a computerized automatic feedback system that adjusts light intensity to maintain a constant-response amplitude to a flickering stimulus throughout the spectrum, as it is scanned from 300 to 700 nm, and back. The results are presented as the reciprocal of the intensity at each wavelength required to maintain a constant peak to peak response amplitude. The resulting S(lambda) had two peaks in all three rodent species, corresponding to ultraviolet and M cones, respectively: 359 nm and 511 nm for mice, 362 nm and 493 nm for gerbils, and 362 nm and 502 nm for rats. Results for mouse and gerbil were similar to literature reports of S(lambda) functions obtained with other methods, confirming that the ERG associated to the AC Constant-Response Method was effective to obtain reliable S(lambda) functions. In addition, due to its fast data collection time, the AC Constant Response Method has the advantage of keeping the eye in a constant light adapted state. PMID- 26800522 TI - Correlating Function and Imaging Measures of the Medial Longitudinal Fasciculus. AB - OBJECTIVE: To test the validity of diffusion tensor imaging (DTI) measures of tissue injury by examining such measures in a white matter structure with well defined function, the medial longitudinal fasciculus (MLF). Injury to the MLF underlies internuclear ophthalmoparesis (INO). METHODS: 40 MS patients with chronic INO and 15 healthy controls were examined under an IRB-approved protocol. Tissue integrity of the MLF was characterized by DTI parameters: longitudinal diffusivity (LD), transverse diffusivity (TD), mean diffusivity (MD) and fractional anisotropy (FA). Severity of INO was quantified by infrared oculography to measure versional disconjugacy index (VDI). RESULTS: LD was significantly lower in patients than in controls in the medulla-pons region of the MLF (p < 0.03). FA was also lower in patients in the same region (p < 0.0004). LD of the medulla-pons region correlated with VDI (R = -0.28, p < 0.05) as did FA in the midbrain section (R = 0.31, p < 0.02). CONCLUSIONS: This study demonstrates that DTI measures of brain tissue injury can detect injury to a functionally relevant white matter pathway, and that such measures correlate with clinically accepted evaluation indices for INO. The results validate DTI as a useful imaging measure of tissue integrity. PMID- 26800523 TI - An Innovative Method of Measuring Changes in Access to Healthful Foods in School Lunch Programs: Findings from a Pilot Evaluation. AB - INTRODUCTION: A large local health department in Colorado partnered with 15 school districts to develop an approach to evaluate changes in access to healthy foods in reimbursable school lunches and a la carte offerings. MATERIALS AND METHODS: School district nutrition managers were engaged at the start of this project. Health department dietitians developed criteria to classify food items as "Lower Fat and less added Sugar" (LFS) and "Higher Fat and more added Sugar" (HFS) based on the percentage of calories from fat and grams of added sugar. Lunch production sheets were obtained for two time periods, food items and the number of planned servings recorded. LFS and HFS planned servings were summed for each time period, and a LFS to HFS ratio calculated by dividing LFS planned servings by HFS planned servings. Additional analyses included calculating LFS: HFS ratios by school district, and for a la carte offerings. RESULTS: In 2009, the LFS: HFS ratio was 2.08, in 2011, 3.71 (P<0.0001). The method also detected changes in ratios at the school district level. For a la carte items, in 2009 the ratio of LFS: HFS was 0.53, and in 2011, 0.61 (not statistically significant). CONCLUSIONS: This method detected an increase in the LFS: HFS ratio over time and demonstrated that the school districts improved access to healthful food/drink by changing the contents of reimbursable school lunches. The evaluation method discussed here can generate information that districts can use in helping sustain and expand their efforts to create healthier environments for children and adults. Although federal regulations now cover all food and beverages served during the school day, there are still opportunities to improve and measure changes in food served in other settings such as child care centers, youth correction facilities, or in schools not participating in the National School Lunch Program. PMID- 26800525 TI - Evaluation of Knee Ligament Mechanics Using Computational Models. AB - The steady maturation of computational biomechanics is providing the musculoskeletal health community with exciting avenues for enhancing orthopedic practice and rehabilitation. Computational knee models deliver tools that may improve the efficiency and outcomes of orthopedic research and methods through analysis of virtual surgeries and devices. They also provide insight into the interaction of knee structures and can predict what cannot be directly measured such as loading on our cartilage and ligaments during movement. This project created subject-specific computational knee models of two young adult females using magnetic resonance imaging-derived knee geometries and passive leg motion measured by a motion capture system. The knee models produced passive ligament lengthening patterns similar to experimental measurements available in the literature. The models also predicted cruciate ligament forces during passive flexion with and without applying anterior-posterior tibia forces that were similar to experimental measurements available in the literature. The biomechanics of the posterior oblique ligament (POL) and the anterior cruciate ligament bundles during combined tibia internal-external rotation torque and anterior-posterior forces through deep flexion were then examined. The study showed that the central arm of the POL: (1) produces a maximum constraining force when the knee is at full extension, (2) constrains internal tibial rotation at extension, and (3) constrains posterior tibial translation at extension. The POL reinforces the constraint of the anterior cruciate ligament to internal rotation at extension and provides constraint for posterior tibial translation at extension, a position where the posterior cruciate ligament provides minimal posterior translation constraint. PMID- 26800524 TI - Effects of Subinhibitory Concentrations of Ceftaroline on Methicillin-Resistant Staphylococcus aureus (MRSA) Biofilms. AB - Ceftaroline (CPT) is a novel cephalosporin with in vitro activity against Staphylococcus aureus. Ceftaroline exhibits a level of binding affinity for PBPs in S. aureus including PBP2a of methicillin-resistant S. aureus (MRSA). The aims of this study were to investigate the morphological, physiological and molecular responses of MRSA clinical strains and MRSA biofilms to sub-MICs (1/4 and 1/16 MIC) of ceftaroline by using transmission, scanning and confocal microscopy. We have also used quantitative Real-Time PCR to study the effect of sub-MICs of ceftaroline on the expression of the staphylococcal icaA, agrA, sarA and sasF genes in MRSA biofilms. In one set of experiments, ceftaroline was able to inhibit biofilm formation in all strains tested at MIC, however, a strain dependent behavior in presence of sub-MICs of ceftaroline was shown. In a second set of experiments, destruction of preformed biofilms by addition of ceftaroline was evaluated. Ceftaroline was able to inhibit biofilm formation at MIC in all strains tested but not at the sub-MICs. Destruction of preformed biofilms was strain dependent because the biofilm formed by a matrix-producing strain was resistant to a challenge with ceftaroline at MIC, whereas in other strains the biofilm was sensitive. At sub-MICs, the impact of ceftaroline on expression of virulence genes was strain-dependent at 1/4 MIC and no correlation between ceftaroline-enhanced biofilm formation and gene regulation was established at 1/16 MIC. Our findings suggest that sub-MICs of ceftaroline enhance bacterial attachment and biofilm formation by some, but not all, MRSA strains and, therefore, stress the importance of maintaining effective bactericidal concentrations of ceftaroline to fight biofilm-MRSA related infections. PMID- 26800528 TI - Nonparametric Feature Matching Based Conditional Random Fields for Gesture Recognition from Multi-Modal Video. AB - We present a new gesture recognition method that is based on the conditional random field (CRF) model using multiple feature matching. Our approach solves the labeling problem, determining gesture categories and their temporal ranges at the same time. A generative probabilistic model is formalized and probability densities are nonparametrically estimated by matching input features with a training dataset. In addition to the conventional skeletal joint-based features, the appearance information near the active hand in an RGB image is exploited to capture the detailed motion of fingers. The estimated likelihood function is then used as the unary term for our CRF model. The smoothness term is also incorporated to enforce the temporal coherence of our solution. Frame-wise recognition results can then be obtained by applying an efficient dynamic programming technique. To estimate the parameters of the proposed CRF model, we incorporate the structured support vector machine (SSVM) framework that can perform efficient structured learning by using large-scale datasets. Experimental results demonstrate that our method provides effective gesture recognition results for challenging real gesture datasets. By scoring 0.8563 in the mean Jaccard index, our method has obtained the state-of-the-art results for the gesture recognition track of the 2014 ChaLearn Looking at People (LAP) Challenge. PMID- 26800526 TI - The Subcellular Dynamics of the Gs-Linked Receptor GPR3 Contribute to the Local Activation of PKA in Cerebellar Granular Neurons. AB - G-protein-coupled receptor (GPR) 3 is a member of the GPR family that constitutively activates adenylate cyclase. We have reported that the expression of GPR3 in cerebellar granular neurons (CGNs) contributes to neurite outgrowth and modulates neuronal proliferation and survival. To further identify its role, we have analyzed the precise distribution and local functions of GPR3 in neurons. The fluorescently tagged GPR3 protein was distributed in the plasma membrane, the Golgi body, and the endosomes. In addition, we have revealed that the plasma membrane expression of GPR3 functionally up-regulated the levels of PKA, as measured by a PKA FRET indicator. Next, we asked if the PKA activity was modulated by the expression of GPR3 in CGNs. PKA activity was highly modulated at the neurite tips compared to the soma. In addition, the PKA activity at the neurite tips was up-regulated when GPR3 was transfected into the cells. However, local PKA activity was decreased when endogenous GPR3 was suppressed by a GPR3 siRNA. Finally, we determined the local dynamics of GPR3 in CGNs using time-lapse analysis. Surprisingly, the fluorescent GPR3 puncta were transported along the neurite in both directions over time. In addition, the anterograde movements of the GPR3 puncta in the neurite were significantly inhibited by actin or microtubule polymerization inhibitors and were also disturbed by the Myosin II inhibitor blebbistatin. Moreover, the PKA activity at the tips of the neurites was decreased when blebbistatin was administered. These results suggested that GPR3 was transported along the neurite and contributed to the local activation of PKA in CGN development. The local dynamics of GPR3 in CGNs may affect local neuronal functions, including neuronal differentiation and maturation. PMID- 26800529 TI - An Accurate and Robust Artificial Marker Based on Cyclic Codes. AB - Artificial markers are successfully adopted to solve several vision tasks, ranging from tracking to calibration. While most designs share the same working principles, many specialized approaches exist to address specific application domains. Some are specially crafted to boost pose recovery accuracy. Others are made robust to occlusion or easy to detect with minimal computational resources. The sheer amount of approaches available in recent literature is indeed a statement to the fact that no silver bullet exists. Furthermore, this is also a hint to the level of scholarly interest that still characterizes this research topic. With this paper we try to add a novel option to the offer, by introducing a general purpose fiducial marker which exhibits many useful properties while being easy to implement and fast to detect. The key ideas underlying our approach are three. The first one is to exploit the projective invariance of conics to jointly find the marker and set a reading frame for it. Moreover, the tag identity is assessed by a redundant cyclic coded sequence implemented using the same circular features used for detection. Finally, the specific design and feature organization of the marker are well suited for several practical tasks, ranging from camera calibration to information payload delivery. PMID- 26800527 TI - Dynamic Sumoylation of a Conserved Transcription Corepressor Prevents Persistent Inclusion Formation during Hyperosmotic Stress. AB - Cells are often exposed to physical or chemical stresses that can damage the structures of essential biomolecules. Stress-induced cellular damage can become deleterious if not managed appropriately. Rapid and adaptive responses to stresses are therefore crucial for cell survival. In eukaryotic cells, different stresses trigger post-translational modification of proteins with the small ubiquitin-like modifier SUMO. However, the specific regulatory roles of sumoylation in each stress response are not well understood. Here, we examined the sumoylation events that occur in budding yeast after exposure to hyperosmotic stress. We discovered by proteomic and biochemical analyses that hyperosmotic stress incurs the rapid and transient sumoylation of Cyc8 and Tup1, which together form a conserved transcription corepressor complex that regulates hundreds of genes. Gene expression and cell biological analyses revealed that sumoylation of each protein directs distinct outcomes. In particular, we discovered that Cyc8 sumoylation prevents the persistence of hyperosmotic stress induced Cyc8-Tup1 inclusions, which involves a glutamine-rich prion domain in Cyc8. We propose that sumoylation protects against persistent inclusion formation during hyperosmotic stress, allowing optimal transcriptional function of the Cyc8 Tup1 complex. PMID- 26800530 TI - Texture Feature Extraction and Analysis for Polyp Differentiation via Computed Tomography Colonography. AB - Image textures in computed tomography colonography (CTC) have great potential for differentiating non-neoplastic from neoplastic polyps and thus can advance the current CTC detection-only paradigm to a new level with diagnostic capability. However, image textures are frequently compromised, particularly in low-dose CT imaging. Furthermore, texture feature extraction may vary, depending on the polyp spatial orientation variation, resulting in variable results. To address these issues, this study proposes an adaptive approach to extract and analyze the texture features for polyp differentiation. Firstly, derivative (e.g. gradient and curvature) operations are performed on the CT intensity image to amplify the textures with adequate noise control. Then Haralick co-occurrence matrix (CM) is used to calculate texture measures along each of the 13 directions (defined by the first and second order image voxel neighbors) through the polyp volume in the intensity, gradient and curvature images. Instead of taking the mean and range of each CM measure over the 13 directions as the so-called Haralick texture features, Karhunen-Loeve transform is performed to map the 13 directions into an orthogonal coordinate system so that the resulted texture features are less dependent on the polyp orientation variation. These simple ideas for amplifying textures and stabilizing spatial variation demonstrated a significant impact for the differentiating task by experiments using 384 polyp datasets, of which 52 are non-neoplastic polyps and the rest are neoplastic polyps. By the merit of area under the curve of receiver operating characteristic, the innovative ideas achieved differentiation capability of 0.8016, indicating the CTC diagnostic feasibility. PMID- 26800532 TI - Statistical Modeling of Retinal Optical Coherence Tomography. AB - In this paper, a new model for retinal Optical Coherence Tomography (OCT) images is proposed. This statistical model is based on introducing a nonlinear Gaussianization transform to convert the probability distribution function (pdf) of each OCT intra-retinal layer to a Gaussian distribution. The retina is a layered structure and in OCT each of these layers has a specific pdf which is corrupted by speckle noise, therefore a mixture model for statistical modeling of OCT images is proposed. A Normal-Laplace distribution, which is a convolution of a Laplace pdf and Gaussian noise, is proposed as the distribution of each component of this model. The reason for choosing Laplace pdf is the monotonically decaying behavior of OCT intensities in each layer for healthy cases. After fitting a mixture model to the data, each component is gaussianized and all of them are combined by Averaged Maximum A Posterior (AMAP) method. To demonstrate the ability of this method, a new contrast enhancement method based on this statistical model is proposed and tested on thirteen healthy 3D OCTs taken by the Topcon 3D OCT and five 3D OCTs from Age-related Macular Degeneration (AMD) patients, taken by Zeiss Cirrus HD-OCT. Comparing the results with two contending techniques, the prominence of the proposed method is demonstrated both visually and numerically. Furthermore, to prove the efficacy of the proposed method for a more direct and specific purpose, an improvement in the segmentation of intra retinal layers using the proposed contrast enhancement method as a preprocessing step, is demonstrated. PMID- 26800531 TI - Accurate Segmentation of CT Male Pelvic Organs via Regression-Based Deformable Models and Multi-Task Random Forests. AB - Segmenting male pelvic organs from CT images is a prerequisite for prostate cancer radiotherapy. The efficacy of radiation treatment highly depends on segmentation accuracy. However, accurate segmentation of male pelvic organs is challenging due to low tissue contrast of CT images, as well as large variations of shape and appearance of the pelvic organs. Among existing segmentation methods, deformable models are the most popular, as shape prior can be easily incorporated to regularize the segmentation. Nonetheless, the sensitivity to initialization often limits their performance, especially for segmenting organs with large shape variations. In this paper, we propose a novel approach to guide deformable models, thus making them robust against arbitrary initializations. Specifically, we learn a displacement regressor, which predicts 3D displacement from any image voxel to the target organ boundary based on the local patch appearance. This regressor provides a non-local external force for each vertex of deformable model, thus overcoming the initialization problem suffered by the traditional deformable models. To learn a reliable displacement regressor, two strategies are particularly proposed. 1) A multi-task random forest is proposed to learn the displacement regressor jointly with the organ classifier; 2) an auto context model is used to iteratively enforce structural information during voxel wise prediction. Extensive experiments on 313 planning CT scans of 313 patients show that our method achieves better results than alternative classification or regression based methods, and also several other existing methods in CT pelvic organ segmentation. PMID- 26800533 TI - Mixed Spectrum Analysis on fMRI Time-Series. AB - Temporal autocorrelation present in functional magnetic resonance image (fMRI) data poses challenges to its analysis. The existing approaches handling autocorrelation in fMRI time-series often presume a specific model of autocorrelation such as an auto-regressive model. The main limitation here is that the correlation structure of voxels is generally unknown and varies in different brain regions because of different levels of neurogenic noises and pulsatile effects. Enforcing a universal model on all brain regions leads to bias and loss of efficiency in the analysis. In this paper, we propose the mixed spectrum analysis of the voxel time-series to separate the discrete component corresponding to input stimuli and the continuous component carrying temporal autocorrelation. A mixed spectral analysis technique based on M-spectral estimator is proposed, which effectively removes autocorrelation effects from voxel time-series and identify significant peaks of the spectrum. As the proposed method does not assume any prior model for the autocorrelation effect in voxel time-series, varying correlation structure among the brain regions does not affect its performance. We have modified the standard M-spectral method for an application on a spatial set of time-series by incorporating the contextual information related to the continuous spectrum of neighborhood voxels, thus reducing considerably the computation cost. Likelihood of the activation is predicted by comparing the amplitude of discrete component at stimulus frequency of voxels across the brain by using normal distribution and modeling spatial correlations among the likelihood with a conditional random field. We also demonstrate the application of the proposed method in detecting other desired frequencies. PMID- 26800534 TI - Avoiding Aliasing in Allan Variance: An Application to Fiber Link Data Analysis. AB - Optical fiber links are known as the most performing tools to transfer ultrastable frequency reference signals. However, these signals are affected by phase noise up to bandwidths of several kilohertz and a careful data processing strategy is required to properly estimate the uncertainty. This aspect is often overlooked and a number of approaches have been proposed to implicitly deal with it. Here, we face this issue in terms of aliasing and show how typical tools of signal analysis can be adapted to the evaluation of optical fiber links performance. In this way, it is possible to use the Allan variance (AVAR) as estimator of stability and there is no need to introduce other estimators. The general rules we derive can be extended to all optical links. As an example, we apply this method to the experimental data we obtained on a 1284-km coherent optical link for frequency dissemination, which we realized in Italy. PMID- 26800535 TI - On the Design of Attitude-Heading Reference Systems Using the Allan Variance. AB - The Allan variance is a method to characterize stochastic random processes. The technique was originally developed to characterize the stability of atomic clocks and has also been successfully applied to the characterization of inertial sensors. Inertial navigation systems (INS) can provide accurate results in a short time, which tend to rapidly degrade in longer time intervals. During the last decade, the performance of inertial sensors has significantly improved, particularly in terms of signal stability, mechanical robustness, and power consumption. The mass and volume of inertial sensors have also been significantly reduced, offering system-level design and accommodation advantages. This paper presents a complete methodology for the characterization and modeling of inertial sensors using the Allan variance, with direct application to navigation systems. Although the concept of sensor fusion is relatively straightforward, accurate characterization and sensor-information filtering is not a trivial task, yet they are essential for good performance. A complete and reproducible methodology utilizing the Allan variance, including all the intermediate steps, is described. An end-to-end (E2E) process for sensor-error characterization and modeling up to the final integration in the sensor-fusion scheme is explained in detail. The strength of this approach is demonstrated with representative tests on novel, high-grade inertial sensors. Experimental navigation results are presented from two distinct robotic applications: a planetary exploration rover prototype and an autonomous underwater vehicle (AUV). PMID- 26800536 TI - Transform-Based Channel-Data Compression to Improve the Performance of a Real Time GPU-Based Software Beamformer. AB - Graphics processing unit (GPU)-based software beamforming has advantages over hardware-based beamforming of easier programmability and a faster design cycle, since complicated imaging algorithms can be efficiently programmed and modified. However, the need for a high data rate when transferring ultrasound radio frequency (RF) data from the hardware front end to the software back end limits the real-time performance. Data compression methods can be applied to the hardware front end to mitigate the data transfer issue. Nevertheless, most decompression processes cannot be performed efficiently on a GPU, thus becoming another bottleneck of the real-time imaging. Moreover, lossless (or nearly lossless) compression is desirable to avoid image quality degradation. In a previous study, we proposed a real-time lossless compression-decompression algorithm and demonstrated that it can reduce the overall processing time because the reduction in data transfer time is greater than the computation time required for compression/decompression. This paper analyzes the lossless compression method in order to understand the factors limiting the compression efficiency. Based on the analytical results, a nearly lossless compression is proposed to further enhance the compression efficiency. The proposed method comprises a transformation coding method involving modified lossless compression that aims at suppressing amplitude data. The simulation results indicate that the compression ratio (CR) of the proposed approach can be enhanced from nearly 1.8 to 2.5, thus allowing a higher data acquisition rate at the front end. The spatial and contrast resolutions with and without compression were almost identical, and the process of decompressing the data of a single frame on a GPU took only several milliseconds. Moreover, the proposed method has been implemented in a 64-channel system that we built in-house to demonstrate the feasibility of the proposed algorithm in a real system. It was found that channel data from a 64-channel system can be transferred using the standard USB 3.0 interface in most practical imaging applications. PMID- 26800537 TI - A Forward Regridding Method With Minimal Oversampling for Accurate and Efficient Iterative Tomographic Algorithms. AB - Reconstruction of underconstrained tomographic data sets remains a major challenge. Standard analytical techniques frequently lead to unsatisfactory results due to insufficient information. Several iterative algorithms, which can easily integrate a priori knowledge, have been developed to tackle this problem during the last few decades. Most of these iterative algorithms are based on an implementation of the Radon transform that acts as forward projector. This operator and its adjoint, the backprojector, are typically called few times per iteration and represent the computational bottleneck of the reconstruction process. Here, we present a Fourier-based forward projector, founded on the regridding method with minimal oversampling. We show that this implementation of the Radon transform significantly outperforms in efficiency other state-of-the art operators with O(N2log2N) complexity. Despite its reduced computational cost, this regridding method provides comparable accuracy to more sophisticated projectors and can, therefore, be exploited in iterative algorithms to substantially decrease the time required for the reconstruction of underconstrained tomographic data sets without loss in the quality of the results. PMID- 26800538 TI - An MM-Based Algorithm for l1-Regularized Least-Squares Estimation With an Application to Ground Penetrating Radar Image Reconstruction. AB - An estimation method known as least absolute shrinkage and selection operator (LASSO) or l1-regularized LS estimation has been found to perform well in a number of applications. In this paper, we use the majorize-minimize method to develop an algorithm for minimizing the LASSO objective function, which is the sum of a linear LS objective function plus an l1 penalty term. The proposed algorithm, which we call the LASSO estimation via majorization-minimization (LMM) algorithm, is straightforward to implement, parallelizable, and guaranteed to produce LASSO objective function values that monotonically decrease. In addition, we formulate an extension of the LMM algorithm for reconstructing ground penetrating radar (GPR) images, that is much faster than the standard LMM algorithm and utilizes significantly less memory. Thus, the GPR specific LMM (GPR LMM) algorithm is able to accommodate the big data associated with GPR imaging. We compare our proposed algorithms to the state-of-the-art l1-regularized LS algorithms using a time and space complexity analysis. The GPR-LMM greatly outperforms the competing algorithms in terms of the performance metrics we considered. In addition, the reconstruction results of the standard LMM and GPR LMM algorithms are evaluated using both simulated and real GPR data. PMID- 26800539 TI - Face Alignment via Regressing Local Binary Features. AB - This paper presents a highly efficient and accurate regression approach for face alignment. Our approach has two novel components: 1) a set of local binary features and 2) a locality principle for learning those features. The locality principle guides us to learn a set of highly discriminative local binary features for each facial landmark independently. The obtained local binary features are used to jointly learn a linear regression for the final output. This approach achieves the state-of-the-art results when tested on the most challenging benchmarks to date. Furthermore, because extracting and regressing local binary features are computationally very cheap, our system is much faster than previous methods. It achieves over 3000 frames per second (FPS) on a desktop or 300 FPS on a mobile phone for locating a few dozens of landmarks. We also study a key issue that is important but has received little attention in the previous research, which is the face detector used to initialize alignment. We investigate several face detectors and perform quantitative evaluation on how they affect alignment accuracy. We find that an alignment friendly detector can further greatly boost the accuracy of our alignment method, reducing the error up to 16% relatively. To facilitate practical usage of face detection/alignment methods, we also propose a convenient metric to measure how good a detector is for alignment initialization. PMID- 26800540 TI - Multi-Scale Fusion for Improved Localization of Malicious Tampering in Digital Images. AB - A sliding window-based analysis is a prevailing mechanism for tampering localization in passive image authentication. It uses existing forensic detectors, originally designed for a full-frame analysis, to obtain the detection scores for individual image regions. One of the main problems with a window-based analysis is its impractically low localization resolution stemming from the need to use relatively large analysis windows. While decreasing the window size can improve the localization resolution, the classification results tend to become unreliable due to insufficient statistics about the relevant forensic features. In this paper, we investigate a multi-scale analysis approach that fuses multiple candidate tampering maps, resulting from the analysis with different windows, to obtain a single, more reliable tampering map with better localization resolution. We propose three different techniques for multi-scale fusion, and verify their feasibility against various reference strategies. We consider a popular tampering scenario with mode-based first digit features to distinguish between singly and doubly compressed regions. Our results clearly indicate that the proposed fusion strategies can successfully combine the benefits of small-scale and large-scale analyses and improve the tampering localization performance. PMID- 26800541 TI - BIT: Biologically Inspired Tracker. AB - Visual tracking is challenging due to image variations caused by various factors, such as object deformation, scale change, illumination change, and occlusion. Given the superior tracking performance of human visual system (HVS), an ideal design of biologically inspired model is expected to improve computer visual tracking. This is, however, a difficult task due to the incomplete understanding of neurons' working mechanism in the HVS. This paper aims to address this challenge based on the analysis of visual cognitive mechanism of the ventral stream in the visual cortex, which simulates shallow neurons (S1 units and C1 units) to extract low-level biologically inspired features for the target appearance and imitates an advanced learning mechanism (S2 units and C2 units) to combine generative and discriminative models for target location. In addition, fast Gabor approximation and fast Fourier transform are adopted for real-time learning and detection in this framework. Extensive experiments on large-scale benchmark data sets show that the proposed biologically inspired tracker performs favorably against the state-of-the-art methods in terms of efficiency, accuracy, and robustness. The acceleration technique in particular ensures that biologically inspired tracker maintains a speed of approximately 45 frames/s. PMID- 26800542 TI - De Novo Sequencing Assisted Approach for Characterizing Mixture MS/MS Spectra. AB - Extensive research has been conducted for the computational analysis of mass spectrometry based proteomics data. However, there are still remaining challenges, among which, one particular challenge is the low identification rate of the collected spectral data. A specific contributing factor is the existence of mixture spectra in the collected MS/MS spectra which are generated by the concurrent fragmentation of multiple precursors in one sequencing attempt. The quite frequently observed mixture spectra necessitates the development of effective computational approaches to characterize those non-conventional spectral data. In this research, we proposed an approach for matching the query mixture spectra with a pair of peptide sequences acquired from the protein database by incorporating a special de novo assisted filtration strategy. The experiment results on two different datasets of MS/MS spectra containing mixed ion fragments from multiple peptides demonstrated the efficiency of the integrated filtration strategy in reducing examination space and verified the effectiveness of the proposed matching scheme as well. PMID- 26800543 TI - An Effective Approach for Glycan Structure De Novo Sequencing From HCD Spectra. AB - Mass spectrometry has become a widely used analytical technique for proteomics study because of its high throughput and sensitivity. Among those applications, a specific one is to characterize glycan structure. Glycosylation is a frequently occurred post-translational modification of proteins which is relevant to humans' health. Therefore, it is significant to develop effective computational methods to automate the identification of glycan structures from mass spectral data. In our research, we mathematically formulated the glycan de novo sequencing problem and proposed a heuristic algorithm for glycan de novo sequencing from HCD MS/MS spectra of N-linked glycopeptides. The algorithm proceeds in a carefully designate pathway to construct the best matched tree structure from MS/MS spectrum. Experimental results showed that our proposed approach can effectively identify glycan structures from HCD MS/MS spectra. PMID- 26800544 TI - Predicting Protein Function via Semantic Integration of Multiple Networks. AB - Determining the biological functions of proteins is one of the key challenges in the post-genomic era. The rapidly accumulated large volumes of proteomic and genomic data drives to develop computational models for automatically predicting protein function in large scale. Recent approaches focus on integrating multiple heterogeneous data sources and they often get better results than methods that use single data source alone. In this paper, we investigate how to integrate multiple biological data sources with the biological knowledge, i.e., Gene Ontology (GO), for protein function prediction. We propose a method, called SimNet, to Semantically integrate multiple functional association Networks derived from heterogenous data sources. SimNet firstly utilizes GO annotations of proteins to capture the semantic similarity between proteins and introduces a semantic kernel based on the similarity. Next, SimNet constructs a composite network, obtained as a weighted summation of individual networks, and aligns the network with the kernel to get the weights assigned to individual networks. Then, it applies a network-based classifier on the composite network to predict protein function. Experiment results on heterogenous proteomic data sources of Yeast, Human, Mouse, and Fly show that, SimNet not only achieves better (or comparable) results than other related competitive approaches, but also takes much less time. The Matlab codes of SimNet are available at https://sites.google.com/site/guoxian85/simnet. PMID- 26800545 TI - Systematic Design of a Quorum Sensing-Based Biosensor for Enhanced Detection of Metal Ion in Escherichia Coli. AB - With the recent industrial expansion, heavy metals and other pollutants have increasingly contaminated our living surroundings. The non-degradability of heavy metals may lead to accumulation in food chains and the resulting toxicity could cause damage in organisms. Hence, detection techniques have gradually received attention. In this study, a quorum sensing (QS)-based amplifier is introduced to improve the detection performance of metal ion biosensing. The design utilizes diffusible signal molecules, which freely pass through the cell membrane into the environment to communicate with others. Bacteria cooperate via the cell-cell communication process, thereby displaying synchronous behavior, even if only a minority of the cells detect the metal ion. In order to facilitate the design, the ability of the engineered biosensor to detect metal ion is described in a steady state model. The design can be constructed according to user-oriented specifications by selecting adequate components from corresponding libraries, with the help of a genetic algorithm (GA)-based design method. The experimental results validate enhanced efficiency and detection performance of the quorum sensing-based biosensor of metal ions. PMID- 26800546 TI - A Low-Power ASIC Signal Processor for a Vestibular Prosthesis. AB - A low-power ASIC signal processor for a vestibular prosthesis (VP) is reported. Fabricated with TI 0.35 MUm CMOS technology and designed to interface with implanted inertial sensors, the digitally assisted analog signal processor operates extensively in the CMOS subthreshold region. During its operation the ASIC encodes head motion signals captured by the inertial sensors as electrical pulses ultimately targeted for in-vivo stimulation of vestibular nerve fibers. To achieve this, the ASIC implements a coordinate system transformation to correct for misalignment between natural sensors and implanted inertial sensors. It also mimics the frequency response characteristics and frequency encoding mappings of angular and linear head motions observed at the peripheral sense organs, semicircular canals and otolith. Overall the design occupies an area of 6.22 mm (2) and consumes 1.24 mW when supplied with +/- 1.6 V. PMID- 26800547 TI - On the Design of Passive Resonant Circuits to Measure Local Pulse Wave Velocity in a Stent. AB - In-stent restenosis is a frequent complication after stent implantation. This article investigates the design of a passive sensor system to be integrated into a stent for the detection of an in-stent restenosis by measuring the local pulse wave velocity (PWV). The proposed system uses two resonant circuits consisting of a capacitive pressure sensor and a coil as transponders. The pressure sensors are located at the proximal and distal end of the stent. An alternating external magnetic field with a constant frequency is applied such that the resonance frequencies of the transponders cross the excitation frequency when the pulse wave passes. The time delay between the resonances at the transponders can be captured to obtain the PWV. A model for the measurement system and a correlation between transponder design parameters and minimal resolvable time delay are derived. This correlation is based on the criterion that the 3 dB bandwidth of the transponder resonances may not overlap in the measurement time interval. This correlation can be used to design and analyze a transponder system for the proposed measurement system. In an experiment, in which the pressure sensors have been emulated by varactor diodes, it could be shown that the model is valid and that the criterion is suitable. Finally, the relevant design parameters of the transponders have been identified and their limitations investigated. PMID- 26800548 TI - Ultra-Low Power Dynamic Knob in Adaptive Compressed Sensing Towards Biosignal Dynamics. AB - Compressed sensing (CS) is an emerging sampling paradigm in data acquisition. Its integrated analog-to-information structure can perform simultaneous data sensing and compression with low-complexity hardware. To date, most of the existing CS implementations have a fixed architectural setup, which lacks flexibility and adaptivity for efficient dynamic data sensing. In this paper, we propose a dynamic knob (DK) design to effectively reconfigure the CS architecture by recognizing the biosignals. Specifically, the dynamic knob design is a template based structure that comprises a supervised learning module and a look-up table module. We model the DK performance in a closed analytic form and optimize the design via a dynamic programming formulation. We present the design on a 130 nm process, with a 0.058 mm (2) fingerprint and a 187.88 nJ/event energy consumption. Furthermore, we benchmark the design performance using a publicly available dataset. Given the energy constraint in wireless sensing, the adaptive CS architecture can consistently improve the signal reconstruction quality by more than 70%, compared with the traditional CS. The experimental results indicate that the ultra-low power dynamic knob can provide an effective adaptivity and improve the signal quality in compressed sensing towards biosignal dynamics. PMID- 26800549 TI - A Circadian and Cardiac Intraocular Pressure Sensor for Smart Implantable Lens. AB - This paper presents a new system to measure the Intraocular Pressure (IOP) with very high accuracy (0.036 mbar) used for monitoring glaucoma. The system not only monitors the daily variation of the IOP (circadian IOP), but also allows to perform an spectral analysis of the pressure signal generated by the heartbeat (cardiac IOP). The system comprises a piezoresistive pressure sensor, an application-specific integrated circuit (ASIC) to read out the sensor data and an external reader installed on customized glasses. The ASIC readout electronics combines chopping modulation with correlated double sampling (CDS) in order to eliminate both the amplifier offset and the chopper ripple at the sampling frequency. In addition, programmable current sources are used to compensate for the atmospheric pressure ( 800-1200 mbar ) and the circadian component (+/- 7 mbar) thus allowing to read out the very weak cardiac signals (+/- 1.6 mbar) with a maximum accuracy of 0.036 mbar. PMID- 26800550 TI - A Smart CMOS Assay SoC for Rapid Blood Screening Test of Risk Prediction. AB - A micro-controller unit (MCU) assisted immunoassay lab-on-a-chip is realized in 0.35 MUm CMOS technology. The MCU automatically controls the detection procedure including blood filtration through a nonporous aluminum oxide membrane, bimolecular conjugation with antibodies attached to magnetic beads, electrolytic pumping, magnetic flushing and threshold detection based on Hall sensor array readout analysis. To verify the function of this chip, in-vitro Tumor necrosis factor- alpha (TNF-alpha) and N-terminal pro-brain natriuretic peptide (NT proBNP) tests are performed by this 9 mm(2)-sized single chip. The cost, efficiency and portability are considerably improved compared to the prior art. PMID- 26800551 TI - Hierarchical Change-Detection Tests. AB - We present hierarchical change-detection tests (HCDTs), as effective online algorithms for detecting changes in datastreams. HCDTs are characterized by a hierarchical architecture composed of a detection layer and a validation layer. The detection layer steadily analyzes the input datastream by means of an online, sequential CDT, which operates as a low-complexity trigger that promptly detects possible changes in the process generating the data. The validation layer is activated when the detection one reveals a change, and performs an offline, more sophisticated analysis on recently acquired data to reduce false alarms. Our experiments show that, when the process generating the datastream is unknown, as it is mostly the case in the real world, HCDTs achieve a far more advantageous tradeoff between false-positive rate and detection delay than their single layered, more traditional counterpart. Moreover, the successful interplay between the two layers permits HCDTs to automatically reconfigure after having detected and validated a change. Thus, HCDTs are able to reveal further departures from the postchange state of the data-generating process. PMID- 26800552 TI - Bottom-Up Visual Saliency Estimation With Deep Autoencoder-Based Sparse Reconstruction. AB - Research on visual perception indicates that the human visual system is sensitive to center-surround (C-S) contrast in the bottom-up saliency-driven attention process. Different from the traditional contrast computation of feature difference, models based on reconstruction have emerged to estimate saliency by starting from original images themselves instead of seeking for certain ad hoc features. However, in the existing reconstruction-based methods, the reconstruction parameters of each area are calculated independently without taking their global correlation into account. In this paper, inspired by the powerful feature learning and data reconstruction ability of deep autoencoders, we construct a deep C-S inference network and train it with the data sampled randomly from the entire image to obtain a unified reconstruction pattern for the current image. In this way, global competition in sampling and learning processes can be integrated into the nonlocal reconstruction and saliency estimation of each pixel, which can achieve better detection results than the models with separate consideration on local and global rarity. Moreover, by learning from the current scene, the proposed model can achieve the feature extraction and interaction simultaneously in an adaptive way, which can form a better generalization ability to handle more types of stimuli. Experimental results show that in accordance with different inputs, the network can learn distinct basic features for saliency modeling in its code layer. Furthermore, in a comprehensive evaluation on several benchmark data sets, the proposed method can outperform the existing state-of-the-art algorithms. PMID- 26800553 TI - Growing Echo-State Network With Multiple Subreservoirs. AB - An echo-state network (ESN) is an effective alternative to gradient methods for training recurrent neural network. However, it is difficult to determine the structure (mainly the reservoir) of the ESN to match with the given application. In this paper, a growing ESN (GESN) is proposed to design the size and topology of the reservoir automatically. First, the GESN makes use of the block matrix theory to add hidden units to the existing reservoir group by group, which leads to a GESN with multiple subreservoirs. Second, every subreservoir weight matrix in the GESN is created with a predefined singular value spectrum, which ensures the echo-sate property of the ESN without posterior scaling of the weights. Third, during the growth of the network, the output weights of the GESN are updated in an incremental way. Moreover, the convergence of the GESN is proved. Finally, the GESN is tested on some artificial and real-world time-series benchmarks. Simulation results show that the proposed GESN has better prediction performance and faster leaning speed than some ESNs with fixed sizes and topologies. PMID- 26800554 TI - Dynamic Energy Management System for a Smart Microgrid. AB - This paper presents the development of an intelligent dynamic energy management system (I-DEMS) for a smart microgrid. An evolutionary adaptive dynamic programming and reinforcement learning framework is introduced for evolving the I DEMS online. The I-DEMS is an optimal or near-optimal DEMS capable of performing grid-connected and islanded microgrid operations. The primary sources of energy are sustainable, green, and environmentally friendly renewable energy systems (RESs), e.g., wind and solar; however, these forms of energy are uncertain and nondispatchable. Backup battery energy storage and thermal generation were used to overcome these challenges. Using the I-DEMS to schedule dispatches allowed the RESs and energy storage devices to be utilized to their maximum in order to supply the critical load at all times. Based on the microgrid's system states, the I-DEMS generates energy dispatch control signals, while a forward-looking network evaluates the dispatched control signals over time. Typical results are presented for varying generation and load profiles, and the performance of I-DEMS is compared with that of a decision tree approach-based DEMS (D-DEMS). The robust performance of the I-DEMS was illustrated by examining microgrid operations under different battery energy storage conditions. PMID- 26800555 TI - Toward Monitoring Parkinson's Through Analysis of Static Handwriting Samples: A Quantitative Analytical Framework. AB - Detection of changes in micrographia as a manifestation of symptomatic progression or therapeutic response in Parkinson's disease (PD) is challenging as such changes can be subtle. A computerized toolkit based on quantitative analysis of handwriting samples would be valuable as it could supplement and support clinical assessments, help monitor micrographia, and link it to PD. Such a toolkit would be especially useful if it could detect subtle yet relevant changes in handwriting morphology, thus enhancing resolution of the detection procedure. This would be made possible by developing a set of metrics sensitive enough to detect and discern micrographia with specificity. Several metrics that are sensitive to the characteristics of micrographia were developed, with minimal sensitivity to confounding handwriting artifacts. These metrics capture character size-reduction, ink utilization, and pixel density within a writing sample from left to right. They are used here to "score" handwritten signatures of 12 different individuals corresponding to healthy and symptomatic PD conditions, and sample control signatures that had been artificially reduced in size for comparison purposes. Moreover, metric analyses of samples from ten of the 12 individuals for which clinical diagnosis time is known show considerable informative variations when applied to static signature samples obtained before and after diagnosis. In particular, a measure called pixel density variation showed statistically significant differences ( ) between two comparison groups of remote signature recordings: earlier versus recent, based on independent and paired t-test analyses on a total of 40 signature samples. The quantitative framework developed here has the potential to be used in future controlled experiments to study micrographia and links to PD from various aspects, including monitoring and assessment of applied interventions and treatments. The inherent value in this methodology is further enhanced by its reliance solely on static signatures, not requiring dynamic sampling with specialized equipment. PMID- 26800557 TI - Speeding-Up Association Rule Mining With Inverted Index Compression. AB - The growing interest in data storage has made the data size to be exponentially increased, hampering the process of knowledge discovery from these large volumes of high-dimensional and heterogeneous data. In recent years, many efficient algorithms for mining data associations have been proposed, facing up time and main memory requirements. Nevertheless, this mining process could still become hard when the number of items and records is extremely high. In this paper, the goal is not to propose new efficient algorithms but a new data structure that could be used by a variety of existing algorithms without modifying its original schema. Thus, our aim is to speed up the association rule mining process regardless the algorithm used to this end, enabling the performance of efficient implementations to be enhanced. The structure simplifies, reorganizes, and speeds up the data access by sorting data by means of a shuffling strategy based on the hamming distance, which achieve similar values to be closer, and considering both an inverted index mapping and a run length encoding compression. In the experimental study, we explore the bounds of the algorithms' performance by using a wide number of data sets that comprise either thousands or millions of both items and records. The results demonstrate the utility of the proposed data structure in enhancing the algorithms' runtime orders of magnitude, and substantially reducing both the auxiliary and the main memory requirements. PMID- 26800556 TI - Evaluation of Three Algorithms for the Segmentation of Overlapping Cervical Cells. AB - In this paper, we introduce and evaluate the systems submitted to the first Overlapping Cervical Cytology Image Segmentation Challenge, held in conjunction with the IEEE International Symposium on Biomedical Imaging 2014. This challenge was organized to encourage the development and benchmarking of techniques capable of segmenting individual cells from overlapping cellular clumps in cervical cytology images, which is a prerequisite for the development of the next generation of computer-aided diagnosis systems for cervical cancer. In particular, these automated systems must detect and accurately segment both the nucleus and cytoplasm of each cell, even when they are clumped together and, hence, partially occluded. However, this is an unsolved problem due to the poor contrast of cytoplasm boundaries, the large variation in size and shape of cells, and the presence of debris and the large degree of cellular overlap. The challenge initially utilized a database of 16 high-resolution ( *40 magnification) images of complex cellular fields of view, in which the isolated real cells were used to construct a database of 945 cervical cytology images synthesized with a varying number of cells and degree of overlap, in order to provide full access of the segmentation ground truth. These synthetic images were used to provide a reliable and comprehensive framework for quantitative evaluation on this segmentation problem. Results from the submitted methods demonstrate that all the methods are effective in the segmentation of clumps containing at most three cells, with overlap coefficients up to 0.3. This highlights the intrinsic difficulty of this challenge and provides motivation for significant future improvement. PMID- 26800558 TI - I-Ching Divination Evolutionary Algorithm and its Convergence Analysis. AB - An innovative simulated evolutionary algorithm (EA), called I-Ching divination EA (IDEA), and its convergence analysis are proposed and investigated in this paper. Inherited from ancient Chinese culture, I-Ching divination has always been used as a divination system in traditional and modern China. There are three operators evolved from I-Ching transformations in this new optimization algorithm, intrication operator, turnover operator, and mutual operator. These new operators are very flexible in the evolution procedure. Additionally, two new spaces are defined in this paper, which are denoted as hexagram space and state space. In order to analyze the convergence property of I-Ching divination algorithm, Markov model was adopted to analyze the characters of the operators. Meanwhile, the proposed algorithm is proved to be a homogeneous Markov chain with the positive transition matrix. After giving some basic concepts of necessary theorems, definition of admissible functions and I-Ching map, a precise proof of the states converge to the global optimum is presented. Compared with the genetic algorithm, particle swarm optimization, and differential evolution algorithm, our proposed IDEA is much faster in reaching the global optimum. PMID- 26800559 TI - Differential Evolution With Event-Triggered Impulsive Control. AB - Differential evolution (DE) is a simple but powerful evolutionary algorithm, which has been widely and successfully used in various areas. In this paper, an event-triggered impulsive (ETI) control scheme is introduced to improve the performance of DE. Impulsive control (IPC), the concept of which derives from control theory, aims at regulating the states of a network by instantly adjusting the states of a fraction of nodes at certain instants, and these instants are determined by event-triggered mechanism (ETM). By introducing IPC and ETM into DE, we hope to change the search performance of the population in a positive way after revising the positions of some individuals at certain moments. At the end of each generation, the IPC operation is triggered when the update rate of the population declines or equals to zero. In detail, inspired by the concepts of IPC, two types of impulses are presented within the framework of DE in this paper: 1) stabilizing impulses and 2) destabilizing impulses. Stabilizing impulses help the individuals with lower rankings instantly move to a desired state determined by the individuals with better fitness values. Destabilizing impulses randomly alter the positions of inferior individuals within the range of the current population. By means of intelligently modifying the positions of a part of individuals with these two kinds of impulses, both exploitation and exploration abilities of the whole population can be meliorated. In addition, the proposed ETI is flexible to be incorporated into several state-of-the-art DE variants. Experimental results over the IEEE Congress on Evolutionary Computation (CEC) 2014 benchmark functions exhibit that the developed scheme is simple yet effective, which significantly improves the performance of the considered DE algorithms. PMID- 26800560 TI - Norm Monitoring Under Partial Action Observability. AB - In the context of using norms for controlling multiagent systems, a vitally important question that has not yet been addressed in the literature is the development of mechanisms for monitoring norm compliance under partial action observability. This paper proposes the reconstruction of unobserved actions to tackle this problem. In particular, we formalize the problem of reconstructing unobserved actions, and propose an information model and algorithms for monitoring norms under partial action observability using two different processes for reconstructing unobserved actions. Our evaluation shows that reconstructing unobserved actions increases significantly the number of norm violations and fulfilments detected. PMID- 26800561 TI - Endothelial Dysfunction in Human Diabetes Is Mediated by Wnt5a-JNK Signaling. AB - OBJECTIVE: Endothelial dysfunction is linked to insulin resistance, inflammatory activation, and increased cardiovascular risk in diabetes mellitus; however, the mechanisms remain incompletely understood. Recent studies have identified proinflammatory signaling of wingless-type family member (Wnt) 5a through c-jun N terminal kinase (JNK) as a regulator of metabolic dysfunction with potential relevance to vascular function. We sought to gain evidence that increased activation of Wnt5a-JNK signaling contributes to impaired endothelial function in patients with diabetes mellitus. APPROACH AND RESULTS: We measured flow-mediated dilation of the brachial artery and characterized freshly isolated endothelial cells by protein expression, eNOS activation, and nitric oxide production in 85 subjects with type 2 diabetes mellitus (n=42) and age- and sex-matched nondiabetic controls (n=43) and in human aortic endothelial cells treated with Wnt5a. Endothelial cells from patients with diabetes mellitus displayed 1.3-fold higher Wnt5a levels (P=0.01) along with 1.4-fold higher JNK activation (P<0.01) without a difference in total JNK levels. Higher JNK activation was associated with lower flow-mediated dilation, consistent with endothelial dysfunction (r=0.53, P=0.02). Inhibition of Wnt5a and JNK signaling restored insulin and A23187-mediated eNOS activation and improved nitric oxide production in endothelial cells from patients with diabetes mellitus. In endothelial cells from nondiabetic controls, rWnt5a treatment inhibited eNOS activation replicating the diabetic endothelial phenotype. In human aortic endothelial cells, Wnt5a-induced impairment of eNOS activation and nitric oxide production was reversed by Wnt5a and JNK inhibition. CONCLUSIONS: Our findings demonstrate that noncanonical Wnt5a signaling and JNK activity contribute to vascular insulin resistance and endothelial dysfunction and may represent a novel therapeutic opportunity to protect the vasculature in patients with diabetes mellitus. PMID- 26800562 TI - Smooth Muscle Hypoxia-Inducible Factor 1alpha Links Intravascular Pressure and Atherosclerosis--Brief Report. AB - OBJECTIVE: We hypothesized that the hypoxia-inducible factor (HIF) 1alpha in vascular smooth muscle contributes to the development of atherosclerosis, and links intravascular pressure to this process. APPROACH AND RESULTS: Transverse aortic constriction was used to create high-pressure vascular segments in control, apolipoprotein E (ApoE)(-/-), smooth muscle-HIF1alpha(-/-), and ApoE(-/ )*smooth muscle-HIF1alpha(-/-) double-knockout mice. Transverse aortic constriction selectively induced atherosclerosis in high-pressure vascular segments in young ApoE(-/-) mice on normal chow, including coronary plaques within 1 month. Concomitant deletion of HIF1alpha from smooth muscle significantly reduced vascular inflammation, and attenuated atherosclerosis. CONCLUSIONS: HIF1alpha in vascular smooth muscle plays an important role in the pathogenesis of atherosclerosis, and may provide a mechanistic link between blood pressure, vascular inflammation, and lipid deposition. PMID- 26800563 TI - Factor XI Deficiency Protects Against Atherogenesis in Apolipoprotein E/Factor XI Double Knockout Mice. AB - OBJECTIVE: Atherosclerosis and atherothrombosis are still major causes of mortality in the Western world, even after the widespread use of cholesterol lowering medications. Recently, an association between local thrombin generation and atherosclerotic burden has been reported. Here, we studied the role of factor XI (FXI) deficiency in the process of atherosclerosis in mice. APPROACH AND RESULTS: Apolipoprotein E/FXI double knockout mice, created for the first time in our laboratory. There was no difference in cholesterol levels or lipoprotein profiles between apolipoprotein E knockout and double knockout mice. Nevertheless, in 24-week-old double knockout mice, the atherosclerotic lesion area in the aortic sinus was reduced by 32% (P=0.004) in comparison with apolipoprotein E knockout mice. In 42-week-old double knockout mice, FXI deficiency inhibited atherosclerosis progression significantly in the aortic sinus (25% reduction, P=0.024) and in the aortic arch (49% reduction, P=0.028), with a prominent reduction of macrophage infiltration in the atherosclerotic lesions. CONCLUSIONS: FXI deprivation was shown to slow down atherogenesis in mice. The results suggest that the development of atherosclerosis can be prevented by targeting FXI. PMID- 26800564 TI - Apolipoprotein E Receptor 2 Mediates Activated Protein C-Induced Endothelial Akt Activation and Endothelial Barrier Stabilization. AB - OBJECTIVE: Activated protein C (APC), a plasma serine protease, initiates cell signaling that protects endothelial cells from apoptosis and endothelial barrier disruption. Apolipoprotein E receptor 2 (ApoER2; LRP8) is a receptor known for mediating signaling initiated by reelin in neurons. ApoER2 contributes to APC initiated signaling in monocytic U937 cells. The objective was to determine whether ApoER2 is required for APC's beneficial signaling in the endothelial cell surrogate EA.hy926 line. APPROACH AND RESULTS: We used small interfering RNA and inhibitors to probe requirements for specific receptors for APC's antiapoptotic activity and for phosphorylation of disabled-1 by Src family kinases and of Akt. When small interfering RNA for ApoER2 or endothelial cell protein C receptor or protease activated receptor 1 was used, APC's antiapoptotic activity was ablated, indicating that each of these receptors was required. In EA.hy926 cells, APC induced a 2- to 3-fold increased phosphorylation of Ser473-Akt and Tyr232 disabled-1, a phosphorylation known to trigger disabled-1-mediated signaling in other cell types. Ser473-Akt phosphorylation was inhibited by ApoER2 small interfering RNA or by inhibitors of Src (PP2), phosphatidylinositol-3 kinase (LY303511), and protease activated receptor 1 (SCH79797). ApoER2 small interfering RNA blocked the ability of APC to prevent thrombin-induced endothelial barrier disruption in TransEndothelial Resistance assays. Binding studies using purified APC and purified immobilized wild-type and mutated ApoER2 ectodomains suggested that APC binding involves Lys49, Asp50, and Trp64 on the surface of the N-terminal LA1 domain of ApoER2. CONCLUSIONS: ApoER2 contributes cooperatively with endothelial cell protein C receptor and protease activated receptor 1 to APC-initiated endothelial antiapoptotic and barrier protective signaling. PMID- 26800566 TI - Effects of a TAKE 10! Classroom-Based Physical Activity Intervention on Third- to Fifth-Grade Children's On-task Behavior. AB - BACKGROUND: Prolonged sitting at desks during the school day without a break may result in off-task behavior in students. This study was designed to examine the effects of a classroom physical activity intervention, using TAKE 10!, on elementary school students' on-task behavior. Nine classes (3rd to 5th grades) from 1 elementary school participated in the program (4-week baseline and 8-week intervention). METHODS: The students' on-task behavior was measured using systematic direct observation. Observations occurred once a week during weeks 1 to 4 (baseline) and weeks 8 to 12 (intervention). A two-way repeated-measures analysis of variance was used to compare on-task behavior between observation periods. RESULTS: There was a significant decrease (P = .001) in mean percentage on-task behavior from preno TAKE 10! (91.2 +/- 3.4) to postno TAKE 10! (83.5 +/- 4.0) during the baseline period, whereas there was a significant increase (P = .001) in mean percentage on-task behavior from pre-TAKE 10! (82.3 +/- 4.5) to post-TAKE 10! (89.5 +/- 2.7) during the intervention period. CONCLUSIONS: Furthermore, students who received more daily TAKE 10! were found to be more on task than students who received less TAKE 10!. The TAKE 10! program is effective in improving students' on-task behavior in the classroom. PMID- 26800565 TI - Discoidin Domain Receptor-1 Regulates Calcific Extracellular Vesicle Release in Vascular Smooth Muscle Cell Fibrocalcific Response via Transforming Growth Factor beta Signaling. AB - OBJECTIVE: Collagen accumulation and calcification are major determinants of atherosclerotic plaque stability. Extracellular vesicle (EV)-derived microcalcifications in the collagen-poor fibrous cap may promote plaque rupture. In this study, we hypothesize that the collagen receptor discoidin domain receptor-1 (DDR-1) regulates collagen deposition and release of calcifying EVs by vascular smooth muscle cells (SMCs) through the transforming growth factor-beta (TGF-beta) pathway. APPROACH AND RESULTS: SMCs from the carotid arteries of DDR 1(-/-) mice and wild-type littermates (n=5-10 per group) were cultured in normal or calcifying media. At days 14 and 21, SMCs were harvested and EVs isolated for analysis. Compared with wild-type, DDR-1(-/-) SMCs exhibited a 4-fold increase in EV release (P<0.001) with concomitantly elevated alkaline phosphatase activity (P<0.0001) as a hallmark of EV calcifying potential. The DDR-1(-/-) phenotype was characterized by increased mineralization (Alizarin Red S and Osteosense, P<0.001 and P=0.002, respectively) and amorphous collagen deposition (P<0.001). We further identified a novel link between DDR-1 and the TGF-beta pathway previously implicated in both fibrotic and calcific responses. An increase in TGF-beta1 release by DDR-1(-/-) SMCs in calcifying media (P<0.001) stimulated p38 phosphorylation (P=0.02) and suppressed activation of Smad3. Inhibition of either TGF-beta receptor-I or phospho-p38 reversed the fibrocalcific DDR-1(-/-) phenotype, corroborating a causal relationship between DDR-1 and TGF-beta in EV mediated vascular calcification. CONCLUSIONS: DDR-1 interacts with the TGF-beta pathway to restrict calcifying EV-mediated mineralization and fibrosis by SMCs. We therefore establish a novel mechanism of cell-matrix homeostasis in atherosclerotic plaque formation. PMID- 26800567 TI - Sports Participation in Youth as a Predictor of Physical Activity: A 5-Year Longitudinal Study. AB - BACKGROUND: The contribution of sports related factors to predicting long-term physical activity (PA) are unclear. The purpose of this study is to examine tracking of PA during key transition periods in youth and to determine the longitudinal associations between sports club participation and PA. METHODS: Participants (n = 873, baseline age 10 to 18 years) completed self-report surveys in 2009 and 2014 that included the PACE+ PA tool and sports club participation questions. Spearman correlations assessed PA tracking. ANCOVA analyses examined predictors (sports participation at baseline) of PA (follow-up), adjusting for (a) age and sex; and (b) age, sex, and baseline PA. RESULTS: Tracking of PA was weak-to-moderate (rho = .16 to .47). Greater sports participation frequency at baseline significantly predicted PA at follow-up (P < .01). Involvement in club sports at an elite level had a medium-to-large effect on PA levels 5 years later [d = .75 adjusting for (a); d = .60 adjusting for (b)]. CONCLUSION: PA should be promoted in youth as tracking coefficients suggest it can, to an extent, continue into later life. The standard achieved in sport has a role in predicting later PA. PA promotion strategies should include frequent, high quality opportunities for sports participation. PMID- 26800568 TI - Physical Activity States of Preschool-Aged Latino Children in Farmworker Families: Predictive Factors and Relationship With BMI Percentile. AB - BACKGROUND: Obesity disproportionately affects children of Latino farmworkers. Further research is needed to identify patterns of physical activity (PA) in this group and understand how PA affects Body Mass Index (BMI) percentile. METHODS: Two hundred and forty-four participants ages 2.5 to 3.5 in the Ninos Sanos longitudinal study wore accelerometers that measured daily PA. Several PA-related parameters formed a profile for conducting hidden Markov modeling (HMM), which identified different states of PA. RESULTS: Latino farmworker children were generally sedentary. Two different states were selected using HMM-less active and more active. In the more active state; members spent more minutes in moderate vigorous physical activity (MVPA). Most children were in the less active state at any given time; however, switching between states occurred commonly. One variable mother's concern regarding lack of PA-was a marginally significant predictor of membership in the more active state. State did not predict BMI or weight percentile after adjusting for caloric intake. CONCLUSION: Most children demonstrated high amounts of sedentary behavior, and rates of MVPA fell far below recommended levels for both states. The lack of statistically significant results for risk factors and PA state on weight-related outcomes is likely due to the homogeneous behaviors of the children. PMID- 26800569 TI - Patterns and Determinants of Physical Inactivity in Rural and Urban Areas in Peru: A Population-Based Study. AB - BACKGROUND: Physical inactivity and sedentary behaviors have been linked with impaired health outcomes. Establishing the physical inactivity profiles of a given population is needed to establish program targets and to contribute to international monitoring efforts. We report the prevalence of, and explore sociodemographical and built environment factors associated with physical inactivity in 4 resource-limited settings in Peru: rural Puno, urban Puno, Pampas de San Juan de Miraflores (urban), and Tumbes (semiurban). METHODS: Cross sectional analysis of the CRONICAS Cohort Study's baseline assessment. Outcomes of interest were physical inactivity of leisure time (<600 MET-min/week) and transport-related physical activity (not reporting walking or cycling trips) domains of the IPAQ, as well as watching TV, as a proxy of sedentarism (>=2 hours per day). Exposures included demographic factors and perceptions about neighborhood's safety. Associations were explored using Poisson regression models with robust standard errors. Prevalence ratios (PR) and 95% confidence intervals (95% CI) are presented. RESULTS: Data from 3593 individuals were included: 48.5% males, mean age 55.1 (SD: 12.7) years. Physical inactivity was present at rates of 93.7% (95% CI 93.0%-94.5%) and 9.3% (95% CI 8.3%-10.2%) within the leisure time and transport domains, respectively. In addition, 41.7% (95% CI 40.1%-43.3%) of participants reported watching TV for more than 2 hours per day. Rates varied according to study settings (P < .001). In multivariable analysis, being from rural settings was associated with 3% higher prevalence of leisure time physical inactivity relative to highly urban Lima. The pattern was different for transport related physical inactivity: both Puno sites had around 75% to 50% lower prevalence of physical inactivity. Too much traffic was associated with higher levels of transport-related physical inactivity (PR = 1.24; 95% CI 1.01-1.54). CONCLUSION: Our study showed high levels of inactivity and marked contrasting patterns by rural/urban sites. These findings highlight the need to generate synergies to expand nationwide physical activity surveillance systems. PMID- 26800570 TI - The Impact of Mandatory Helmet-Use Legislation on the Frequency of Cycling to School and Helmet Use Among Adolescents. AB - BACKGROUND: This paper analyzes changes in the frequency of cycling to school and helmet wearing after the introduction of a mandatory helmet law, and attempts to identify factors associated with the acceptance of helmet use. METHODS: A mixed method study was designed with a 7-month follow-up period (April 2014 to November 2014). The initial sample included 262 students (aged 12 to 16 years) from Valencia, Spain. The data were collected by questionnaire and 2 focus-group interviews were conducted. RESULTS: No significant changes in cycling-to- school behavior were found during the study period. Cycle helmet use improved, especially among boys, those who used their own bike, and among adolescents who lived within 2 km of school (P < .05 in all cases). The most common reasons given for not using a helmet were social factors. Peer-group pressure had a negative influence on helmet use among adolescents. Participants also indicated that helmet use is inconvenient, in particular among students who used the public bicycle-sharing program. CONCLUSION: The implementation of the helmet-use law did not have a negative impact on the frequency of cycling to school. Our findings provide an empirical basis for designing educational interventions and programs to increase helmet use among adolescents. PMID- 26800571 TI - Physical Activity, Sedentary Time, and Sleep and the Association With Inflammatory Markers and Adiponectin in 8- to 11-Year-Old Danish Children. AB - BACKGROUND: Inflammatory markers, adiponectin, and movement/nonmovement behaviors have all been linked to risk factors for cardiovascular disease; however, the association between childhood movement/nonmovement behaviors and inflammatory markers and adiponectin is unknown. METHODS: We explored the association between accelerometer determined moderate-to-vigorous physical activity (MVPA), sedentary time, and sleep (7 days/8 nights) and fasting C-reactive protein (CRP), interleukin-6 (IL-6), and adiponectin in 806 school children. A sleep variability score was calculated. RESULTS: MVPA was negatively associated with adiponectin in boys and girls (P < .001) and with CRP and IL-6 in girls (P < .05) independent of sleep duration, sedentary time, age, fat mass index (FMI), and pubertal status. Sedentary time was positively associated with adiponectin in boys and girls (both P < .001), and sleep duration with adiponectin in boys independent of age, FMI, and pubertal status (P < .001); however, these associations disappeared after mutual adjustments for movement behavior. Sleep duration variability was positively associated with CRP in girls independent of all covariates (P < .01). CONCLUSION: MVPA remained negatively associated with inflammatory markers and adiponectin, and sleep duration variability positively associated with CRP after adjustment for FMI, pubertal status, and other movement behavior. The inverse association between MVPA and adiponectin conflicts with the anti-inflammatory properties of adiponectin. PMID- 26800573 TI - A Unified Understanding of the Thickness-Dependent Bandgap Transition in Hexagonal Two-Dimensional Semiconductors. AB - Many important layered semiconductors, such as hexagonal boron nitride (hBN) and transition-metal dichalcogenides (TMDs), are derived from a hexagonal lattice. A single layer of such hexagonal semiconductors generally has a direct bandgap at the high-symmetry point K, whereas it becomes an indirect, optically inactive semiconductor as the number of layers increases to two or more. Here, taking hBN and MoS2 as examples, we reveal the microscopic origin of the direct-to-indirect bandgap transition of hexagonal layered materials. Our symmetry analysis and first-principles calculations show that the bandgap transition arises from the lack of the interlayer orbital couplings for the band-edge states at K, which are inherently weak because of the crystal symmetries of hexagonal layered materials. Therefore, it is necessary to judiciously break the underlying crystal symmetries to design more optically active, multilayered semiconductors from hBN or TMDs. PMID- 26800572 TI - Conditional Cytotoxic Anti-HIV Gene Therapy for Selectable Cell Modification. AB - Gene therapy remains one of the potential strategies to achieve a cure for HIV infection. One of the major limitations of anti-HIV gene therapy concerns recovering an adequate number of modified cells to generate an HIV-proof immune system. Our study addresses this issue by developing a methodology that can mark conditional vector-transformed cells for selection and subsequently target HIV infected cells for elimination by treatment with ganciclovir (GCV). We used the herpes simplex virus thymidine kinase (TK) mutant SR39, which is highly potent at killing cells at low GCV concentrations. This gene was cloned into a conditional HIV vector, pNL-GFPRRESA, which expresses the gene of interest as well as green fluorescent protein (GFP) in the presence of HIV Tat protein. We show here that TK-SR39 was more potent that wild-type TK (TK-WT) at eliminating infected cells at lower concentrations of GCV. As the vector expresses GFP in the presence of Tat, transient expression of Tat either by Tat RNA transfection or transduction by a nonintegrating lentiviral (NIL) vector marked the cells with GFP for selection. In cells selected by this strategy, TK-SR39 was more potent at limiting virus replication than TK-WT. Finally, in Jurkat cells modified and selected by this approach, infection with CXCR4-tropic Lai virus could be suppressed by treatment with GCV. GCV treatment limited the number of HIV infected cells, virus production, as well as virus-induced cytopathic effects in this model. We provide proof of principle that TK-SR39 in a conditional HIV vector can provide a safe and effective anti-HIV strategy. PMID- 26800575 TI - Hypertrophic Cardiomyopathy as a Cause of Sudden Cardiac Death in the Young: A Meta-Analysis. AB - BACKGROUND: Sudden cardiac death is often linked with hypertrophic cardiomyopathy in young athletes, but with a divergence of study results. We performed a meta analysis to compare the prevalence of sudden cardiac deaths associated with hypertrophic cardiomyopathy vs sudden cardiac deaths associated with structurally normal hearts. METHODS: A structured search of MEDLINE was conducted for studies published from 1990 through 2014. Retrospective cohort studies, patient registries, and autopsy series examining sudden cardiac death etiology in young individuals (age <=35 years) were included. A random-effects model was applied to generate pooled summary estimates of the percentage of sudden cardiac deaths with structurally normal hearts at postmortem vs those caused by hypertrophic cardiomyopathy. Heterogeneity was assessed using I(2). Subgroup analyses were conducted based on study location, patient age groups, and population types. RESULTS: Thirty-four studies were included, representing a combined sample of 4605 subjects. The overall pooled percentage of sudden cardiac deaths caused by hypertrophic cardiomyopathy was 10.3% (95% confidence interval [CI], 8.0%-12.6%; I(2) = 87.2%), while sudden cardiac deaths with structurally normal hearts at death were more common (P <.001) at 26.7% (95% CI, 21.0%-32.3%; I(2) = 95.3%). In nonathlete subjects, the pooled percentage of sudden cardiac deaths associated with structurally normal hearts (30.7%; 95% CI, 23.0%-38.4%; I(2) = 96.3%) were significantly more common (P <.001) than sudden cardiac death caused by hypertrophic cardiomyopathy (7.8%; 95% CI, 5.8%-9.9%; I(2) = 80.1%). Among athletes, there was no significant difference between summary estimates of hypertrophic cardiomyopathy and structurally normal hearts (P = .57), except in Europe where structurally normal hearts were more common (P = .01). CONCLUSIONS: Hypertrophic cardiomyopathy is not a more common finding at death than structurally normal hearts in young subjects with sudden cardiac death. Increased attention should be directed toward identifying causes of death associated with a structurally normal heart in subjects with sudden cardiac death. PMID- 26800574 TI - Effects of Recombinant Human Bone Morphogenetic Protein-2 Dose and Ceramic Composition on New Bone Formation and Space Maintenance in a Canine Mandibular Ridge Saddle Defect Model. AB - Treatment of mandibular osseous defects is a significant clinical challenge. Maintenance of the height and width of the mandibular ridge is essential for placement of dental implants and restoration of normal dentition. While guided bone regeneration using protective membranes is an effective strategy for maintaining the anatomic contour of the ridge and promoting new bone formation, complications have been reported, including wound failure, seroma, and graft exposure leading to infection. In this study, we investigated injectable low viscosity (LV) polyurethane/ceramic composites augmented with 100 MUg/mL (low) or 400 MUg/mL (high) recombinant human bone morphogenetic protein-2 (rhBMP-2) as space-maintaining bone grafts in a canine mandibular ridge saddle defect model. LV grafts were injected as a reactive paste that set in 5-10 min to form a solid porous composite with bulk modulus exceeding 1 MPa. We hypothesized that compression-resistant LV grafts would enhance new bone formation and maintain the anatomic contour of the mandibular ridge without the use of protective membranes. At the rhBMP-2 dose recommended for the absorbable collagen sponge carrier in dogs (400 MUg/mL), LV grafts maintained the width and height of the host mandibular ridge and supported new bone formation, while at suboptimal (100 MUg/mL) doses, the anatomic contour of the ridge was not maintained. These findings indicate that compression-resistant bone grafts with bulk moduli exceeding 1 MPa and rhBMP-2 doses comparable to that recommended for the collagen sponge carrier support new bone formation and maintain ridge height and width in mandibular ridge defects without protective membranes. PMID- 26800576 TI - Vescalagin from Pink Wax Apple [Syzygium samarangense (Blume) Merrill and Perry] Alleviates Hepatic Insulin Resistance and Ameliorates Glycemic Metabolism Abnormality in Rats Fed a High-Fructose Diet. AB - This study investigates the ameliorative effect of vescalagin (VES) isolated from Pink wax apple fruit on hepatic insulin resistance and abnormal carbohydrate metabolism in high-fructose diet (HFD)-induced hyperglycemic rats. The results show that in HFD rats, VES significantly reduced the values of the area under the curve for glucose in an oral glucose tolerance test and the homeostasis model assessment of insulin resistance index. VES significantly enhanced the activity of hepatic antioxidant enzymes while reducing thiobarbituric acid-reactive substances in HFD rats. Western blot assay revealed that VES reduced hepatic protein expression involved in inflammation pathways while up-regulating expression of hepatic insulin signaling-related proteins. Moreover, VES up regulated the expression of hepatic glycogen synthase and hepatic glycolysis related proteins while down-regulating hepatic gluconeogenesis-related proteins in HFD rats. This study suggests some therapeutic potential of VES in preventing the progression of diabetes mellitus. PMID- 26800619 TI - The Holy Grail--The Quest for Reliable Radiology Requisition Histories. PMID- 26800620 TI - Magnetic Resonance Imaging of Ankle Ligaments. PMID- 26800621 TI - Audit of Atypical Femoral Fractures and a Description of Some of Their Features. AB - PURPOSE: Atypical femoral fractures (AFF) are recently described events related to osteoporosis and, potentially, a rare result of antiresorptive treatment. METHODS: We set out to audit the diagnosis of AFF in an acute hospital. Charts and radiographs were reviewed retrospectively from patients diagnosed with subtrochanteric femoral fractures according to hospital discharge coding at Vancouver General Hospital (VGH), Canada, from January 2005 to March 2013. RESULTS: A total of 3084 patients were discharged from the hospital with a diagnosis of hip fracture between 2005 and 2013. Of these, 204 were coded as having had subtrochanteric fractures; 178 of the patients thus coded had radiographic evidence of other fracture types-usually intertrochanteric fractures. Eleven patients did not have available radiographs. Of the remaining 193 patients whose radiographs were reviewed, 24 (12.4%) fulfilled the published criteria for AFF. OUR OBSERVATIONS WERE: 1) laterality: 13 of 24 AFF (54.2%) were right-sided; 2) there was only one incomplete AFF in this series: a completed fracture was an inclusion criterion, but 1 patient with an AFF had both that fracture and an incomplete fracture and further foci of periosteal or endosteal foci of new bone (PENB) involving the contralateral femur; 3) radiologists had only diagnosed AFF in only 1 of the 24 patients with characteristic radiographic signs of AFF; 4) all but 1 patient had a focus of periosteal and/or endosteal new bone (PENB) through which the fracture line invariably passed, and in the 1 exception the radiography was too poor to be sure of this but there was a symmetrical contralateral focus of PENB; 5) in 19 of 24 patients there was an adequate image of part of the contralateral femur and of these 12 (63%) had a contralateral focus of PENB situated +/-2.5 cm from the index lesion site when measured from the upper aspect of the greater trochanter, and in another patient a prior fracture of the contralateral femur had been treated surgically and it was at a symmetrical contralateral location from the index fracture.; 6) in 3 of the 19 patients multiple foci of PENB were detected on the lateral aspect of the contralateral femur even though the examination was of limited extent; and 7) AFFs were associated with bisphosphonate medication in 75% of the patients studied. CONCLUSIONS: Hospital discharge coding misclassified a great majority of femoral fractures as subtrochanteric. As an essential criteria for diagnosing AFF is their subtrochanteric location, this misclassification impaired our ability to retrospectively search for AFF patients. Radiologists tended not to report AFF when typical radiographic characteristics were present. Bilateral and multifocal disease is of interest in pointing to the diagnosis and in suggesting that the mechanism of injury in respect of these unusual fractures is more complex than simple low-energy trauma. PMID- 26800622 TI - The Management of the Symptomatic Patient With a Metal-on-Metal Hip Prosthesis. AB - Metal-on-metal (MoM) hip implants have gained popularity due to their greater stability and reduction in implant failure compare to metal-on-polyethylene prostheses. However, as well as carrying general risks of hip implantation, risks specifically associated with MoM implants have been well documented in recent years. Conditions such as pseudotumours or aseptic lymphocyte-dominated vasculitis-associated lesions are specific to MoM hip implants. In this review we discuss the typical patient presentation, the investigations that should be performed, the typical findings on various imaging modalities, and the treatment options of symptomatic patients with MoM hip arthroplasties. PMID- 26800623 TI - Factors Correlating Outcome in Young Infants With Congenital Muscular Torticollis. AB - PURPOSE: No previous study using follow-up ultrasonography for evaluating the factors associated with the successful regression of congenital muscular torticollis in young infants has been published. This study aimed to assess clinical factors and sonographic features potentially influencing regression in patients with congenital muscular torticollis. METHODS: From January 2010 to December 2012, 80 infants underwent neck ultrasonography because of clinical suspicion of congenital muscular torticollis. We statistically analysed the correlation between complete resolution and clinicosonographic findings when complete resolution was defined as no visible lesion on follow-up ultrasonography. RESULTS: Of the 80 infants, 61 had congenital muscular torticollis and all were followed up by ultrasonography: 1) 34 underwent physiotherapy, and 27 of them (79.4%) revealed complete resolution in follow-up; 2) 27 did not undergo physiotherapy, and 15 of them (55.6%) showed complete resolution. A statistically significant correlation was found between physiotherapy and complete resolution, but not between complete resolution and patient sex; size, volume, and echogenicity of the lesion; and thickness ratio. CONCLUSIONS: Physiotherapy was the only factor influencing complete resolution in young infants with congenital muscular torticollis. PMID- 26800624 TI - Synergistic anticancer activity of dietary tea polyphenols and bleomycin hydrochloride in human cervical cancer cell: Caspase-dependent and independent apoptotic pathways. AB - Bleomycin is a chemotherapeutic agent that is frequently used in the treatment of various cancers. Bleomycin causes serious adverse effects via antioxidant defense abnormalities against reactive oxygen species (ROS). However, the current cervical cancer monodrug therapy strategy has failed to produce the expected outcomes; hence, combinational therapies are gaining great interest. Tea polyphenols are also effective antioxidative and chemo-preventive agents. However, the combined effect of tea polyphenol (TPP) and bleomycin (BLM) against cervical cancer remains unknown. In this study, we focused on the potential of TPP on BLM anticancer activity against cervical cancer cells. Cervical cancer cells (SiHa) were treated with various concentrations of TPP, BLM and TPP combined with BLM (TPP-BLM), and their effects on cell growth, intracellular reactive oxygen species, poly-caspase activity, early apoptosis and the expression of caspase-3, caspase-8 and caspase-9, Bcl-2 and p53 were assessed. The MTT assay revealed that the SiHa cells were less sensitive to growth inhibition by TPP treatment compared with both BLM and the combination therapy. Nuclear staining indicated that exposure to TPP-BLM increased the percentage of apoptotic nuclei compared with a mono-agent treatment. Caspase activation assay demonstrated that proportion of early and late apoptotic/secondary necrotic cells was higher in the cells treated with the combination therapy than in those treated with either TPP or BLM alone. The TPP-BLM treatment synergistically induced apoptosis through caspase-3, caspase-8 and caspase-9 activation, Bcl-2 upregulation and p53 overexpression. This study suggests that TPP-BLM may be used as an efficient antioxidant-based combination therapy for cervical cancer. PMID- 26800625 TI - Ability Factor Structure Differences In Adulthood And Old Age. AB - Simultaneous maximum likelihood procedures were used in investigate age differences in ability factor structure in adulthood. Data were analyzed for 198 young individuals (age range of 15-32 years), 173 younger old individuals (age range of 51-67 years) and 153 older-old individuals (age range of 68-83 years). Variables were fourteen ability tests marking five cognitive factors: Verbal Comprehension, Number Facility, Perceptual Speed, Symbolic Cognition, and Flexibility of Closure. Results indicated no change in the number of factors and no important shifts in salient loadings. The magnitude of factor covariances, however, tended to increase across age groups. Such shifts were not uniform across factors but appeared to be dependent on the properties of different factors as to whether factor covariance increases were early or late. The results suggested an increasing interdependence of intellectual functioning in late life. PMID- 26800626 TI - The Study Of Multivariate Change Structures: A Conceptual Perspective. AB - Joreskog's LISREL model is applied to the case of longitudinal data. However, instead of postulating causal relationships between individual differences obtained at successive points in time, the developmental model proposed here, assumes causal relationships between initial individual differences and individual differences in subsequent intraindividual changes over a specified time interval. More specifically, causal relationships are postulated at two levels: (a) factor scores, and (b) factor loading patterns. It is possible to define four prototypes of developmental continuity/discontinuity that may characterize actual change phenomena. PMID- 26800627 TI - Guilford's Facet Theory Of Intelligence: An Empirical Comparison Of Models. AB - A general linear model was described for tests constructed in a facet design. Guilford's structure of intellect model and an alternative model were specified as special cases. From the Guilford research seven data sets were selected such that both models could be compared. The comparison was done with oblique and orthogonal factors. Using covariance structure analysis the fit of the models was assessed, and the parameters estimated. Models with orthogonal factors did not fit the data. The fit of the oblique Guilford model was better than the alternative oblique model. For three of the data sets the oblique Guilford model yielded an acceptable fit to the data with parameter estimates that could be interpreted by the structure of intellect model. PMID- 26800628 TI - A Test For Asymmetric Relationships Between Two Reciprocally Related Variables. AB - Recent research has indicated the need for a test to compare the magnitudes of relationships among reciprocally related variables. A test is developed to ascertain whether the difference between the relationship of two reciprocally related variables is significant; the estimates of reciprocal relationships were based on the two-stage least squares (2SLS) analytic procedure. Assumptions and conditions required to conduct the test are discussed, and, since the test employed standardized variables, the use of standardized variables in 2SLS is reviewed. PMID- 26800629 TI - Prior Subject Interest, Students' Evaluations, And Instructional Effectiveness. AB - Students' Prior Subject Interest in a course showed similar correlations with student ratings of instructional effectiveness in two university settings (N = 1102 classes). Correlations between Prior Subject Interest and different dimensions of instructional effectiveness varied from approximately zero to .44. Though these correlations were not high, Prior Subject Interest predicted student ratings better than any of 15 other student/course/instructor characteristics considered (e.g., Expected Grade, Class Size, Workload/Difficulty, Teacher Rank). Instructor self-evaluations of their own teaching effectiveness (N = 329 classes) were also positively correlated with both their own and their students' perceptions of Prior Subject Interest; the dimensions that were most highly correlated -- particularly Learning/Value -- were the same as observed with student ratings. Since both student and instructor self evaluations were similarly related to Prior Subject Interest, it appears that this variable actually affects instructional effectiveness in a way that is accurately reflected in the student ratings. PMID- 26800630 TI - On Using Analysis Of Covariance In Repeated Measures Designs. AB - The use of analysis of covariance in conjunction with the multivariate approach to analyzing repeated measures designs is considered for designs involving between- and within-subject factors, one dependent variable, and one observation per subject on the covariate. Considerations fundamental to a knowledgeable application of ANCOVA in this situation are detailed including issues related to (1) the validity of the test of the main effect of the within-subject factor, (2) the desirability of an interaction between the within-subject factor and the premeasure score, and (3) the reliability of change scores. Tables providing upper bounds on the correlations of the covariate with change scores are provided. Numerical examples illustrating various analyses of repeated measures designs are also presented. PMID- 26800631 TI - Effects Of Role Conflict On Selected Physiological, Affective, And Performance Variables: A Laboratory Simulation. AB - A simulation methodology was employed to assess the cause and effect relationship between role conflict and selected physiological, affective, and performance measures. Multivariate analyses showed that these selected measures do differentiate between individuals exposed to conditions of role conflict and no role conflict. The study indicates the importance of utilizing interdisciplinary dependent measures and supports the use of simulation methodology in studying organizational stress. PMID- 26800632 TI - The effects of a novel psychological attribution and emotional awareness and expression therapy for chronic musculoskeletal pain: A preliminary, uncontrolled trial. AB - OBJECTIVE: Current psychological and behavioral therapies for chronic musculoskeletal pain only modestly reduce pain, disability, and distress. These limited effects may be due to the failure of current therapies: a) to help patients learn that their pain is influenced primarily by central nervous system psychological processes; and b) to enhance awareness and expression of emotions related to psychological trauma or conflict. METHODS: We developed and conducted a preliminary, uncontrolled test of a novel psychological attribution and emotional awareness and expression therapy that involves an initial individual consultation followed by 4 group sessions. A series of 72 patients with chronic musculoskeletal pain had the intervention and were assessed at baseline, post treatment, and 6-month follow-up. RESULTS: Participation and satisfaction were high and attrition was low. Intent-to-treat analyses found significant improvements in hypothesized change processes: psychological attributions for pain, emotional awareness, emotional approach coping, and alexithymia. Pain, interference, depression, and distress showed large effect size improvements at post-treatment, which were maintained or even enhanced at 6 months. Approximately two-thirds of the patients improved at least 30% in pain and other outcomes, and one-third of the patients improved 70%. Changes in attribution and emotional processes predicted outcomes. Higher baseline depressive symptoms predicted greater improvements, and outcomes were comparable for patients with widespread vs. localized pain. CONCLUSION: This novel intervention may lead to greater benefits than available psychological interventions for patients with chronic musculoskeletal pain, but needs controlled testing. PMID- 26800633 TI - Evaluation of the psychometric properties of the PROMIS Cancer Fatigue Short Form with cancer patients. AB - OBJECTIVE: Fatigue is common among cancer patients and adversely impacts quality of life. As such, it is important to measure fatigue accurately in a way that is not burdensome to patients. The 7-item Patient Reported Outcome Measurement Information System (PROMIS) Cancer Fatigue Short Form scale was recently developed using item response theory (IRT). The current study evaluated the psychometric properties of this scale in two samples of cancer patients using classical test theory (CTT). METHODS: Two samples were used: 121 men with prostate cancer and 136 patients scheduled to undergo hematopoietic cell transplantation (HCT) for hematologic cancer. All participants completed the PROMIS Cancer Fatigue Short Form as well as validated measures of fatigue, vitality, and depression. HCT patients also completed measures of anxiety, perceived stress, and a clinical interview designed to identify cases of cancer related fatigue. RESULTS: PROMIS Cancer Fatigue Short Form items loaded on a single factor (CFI=0.948) and the scale demonstrated good internal consistency reliability in both samples (Cronbach's alphas>0.86). Correlations with psychosocial measures were significant (p values<.0001) and in the expected direction, offering evidence for convergent and concurrent validity. PROMIS Fatigue scores were significantly higher in patients who met case definition criteria for cancer-related fatigue (p<.0001), demonstrating criterion validity. CONCLUSION: The current study provides evidence that the PROMIS Cancer Fatigue Short Form is a reliable and valid measure of fatigue in cancer patients. PMID- 26800634 TI - Chronic fatigue syndrome (CFS) symptom-based phenotypes in two clinical cohorts of adult patients in the UK and The Netherlands. AB - OBJECTIVE: Studies have provided evidence of heterogeneity within chronic fatigue syndrome (CFS), but few have used data from large cohorts of CFS patients or replication samples. METHODS: 29 UK secondary-care CFS services recorded the presence/absence of 12 CFS-related symptoms; 8 of these symptoms were recorded by a Dutch tertiary service. Latent Class Analysis (LCA) was used to assign symptom profiles (phenotypes). Regression models were fitted with phenotype as outcome (in relation to age, sex, BMI, duration of illness) and exposure (in relation to comorbidities and patient-reported measures). RESULTS: Data were available for 7041 UK and 1392 Dutch patients. Almost all patients in both cohorts presented with post-exertional malaise, cognitive dysfunction and disturbed/unrefreshing sleep, and these 3 symptoms were excluded from LCA. In UK patients, six phenotypes emerged: 'full' polysymptomatic (median 8, IQR 7-9 symptoms) 32.8%; 'pain-only' (muscle/joint) 20.3%; 'sore throat/painful lymph node' 4.5%; and 'oligosymptomatic' (median 1, IQR 0-2 symptoms) 4.7%. Two 'partial' polysymptomatic phenotypes were similar to the 'full' phenotype, bar absence of dizziness/nausea/palpitations (21.4%) or sore throat/painful lymph nodes (16.3%). Women and patients with longer duration of illness were more likely to be polysymptomatic. Polysymptomatic patients had more severe illness and more comorbidities. LCA restricted to 5 symptoms recorded in both cohorts indicated 3 classes (polysymptomatic, oligosymptomatic, pain-only), which were replicated in Dutch data. CONCLUSIONS: Adults with CFS may have one of 6 symptom-based phenotypes associated with sex, duration and severity of illness, and comorbidity. Future research needs to determine whether phenotypes predict treatment outcomes, and require different treatments. PMID- 26800635 TI - Perceived need for psychosocial support depending on emotional distress and mental comorbidity in men and women with cancer. AB - OBJECTIVE: Although elevated levels of distress are supposed to constitute a need for psychosocial support, the relation between elevated distress and need for support does not appear to be straightforward. We aimed to determine cancer patients' perceived need for psychosocial support, and examine the relation of need to both self-reported emotional distress and the interview-based diagnosis of a mental disorder. METHODS: In a multicenter, cross-sectional study in Germany, 4020 cancer patients (mean age 58 years, 51% women) were evaluated. We obtained self-reports of need for psychosocial support. We measured distress with the National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) and depressive symptoms with the Patient Health Questionnaire (PHQ-9). In a subsample, we evaluated the presence of a mental disorder using the Composite International Diagnostic Interview (CIDI). RESULTS: 32.1% (95%-CI 30.6 to 33.6) of patients perceived a need for psychosocial support. Younger age, female sex, and higher education were associated with more needs, being married and living with a partner with fewer needs, respectively. While up to 51.2% of patients with elevated distress levels reported a need for psychosocial support, up to 26.1% of those without elevated distress levels perceived such a need. Results were similar across distress assessment methods. CONCLUSION: Our findings emphasize that the occurrence of mental distress is one important but not an exclusive factor among different motives to report the need for psychosocial support. We should thus consider multifaceted perspectives, facilitators and barriers when planning and implementing patient-centered psychosocial care services. PMID- 26800636 TI - Catastrophizing misinterpretations predict somatoform-related symptoms and new onsets of somatoform disorders. AB - BACKGROUND: Somatoform disorders are characterized by multiple recurring symptoms that resemble physical illnesses but defy medical explanation. Psychological models suggest that catastrophizing misinterpretations of harmless physical symptoms play a key role. However, the question of whether such biases predict somatoform-related symptoms and the onset of somatoform disorders has not been adressed. Hence, the aim of the present study was to further advance our understanding of the role of catastrophizing misinterpretations in somatoform disorders. METHODS: In the present study, we used data from the Dresden Predictor Study (N=1538), in which an epidemiologic sample of young German women was tested at two time points approximately 17 months apart. Each participant completed a diagnostic interview, an interpretation questionnaire for somatoform and hypochondriacal symptoms, and three measures of such symptomatology: somatization subscale of the Symptom Checklist-90-Revised (SCL-90-R), Whiteley Index (WI), Body Sensations Questionnaire (BSQ). RESULTS: At follow-up, 33 women were diagnosed with new onsets of lifetime somatoform disorder. Results showed that catastrophizing misinterpretations assessed at baseline were predictive of somatoform-related symptoms at follow-up, i.e., symptoms assessed with the WI and BSQ. Moreover, catastrophizing misinterpretations were predictive of new onsets of somatoform disorders, even after controlling for general threat-related misinterpretations and indices of somatoform symptoms (i.e., SCL-90-R and BSQ). CONCLUSIONS: This is the first prospective, longitudinal study to demonstrate that catastrophizing misinterpretations have incremental validity as predictors of future somatoform-related symptomatology and somatoform disorders. PMID- 26800637 TI - Illness perceptions of people with long-term conditions are associated with frequent use of the emergency department independent of mental illness and somatic symptom burden. AB - OBJECTIVE: To determine whether illness perceptions of patients with long-term conditions (LTCs) are associated with urgent healthcare use and whether this association is independent from mental illness and somatic symptom burden. METHODS: Illness perceptions (B-IPQ) and somatic symptom severity (PHQ-15) were assessed in 304 patients with diabetes, rheumatological disorders and COPD attending an Accident and Emergency Department (AED) in Greece over a one year period. The presence of mental illness was determined by the Mini International Neuropsychiatric Interview. A Generalized Linear Model (Negative Binomial) regression was used to determine the associations of illness perceptions with AED use after adjusting for mental illness, somatic symptom severity, disease parameters and demographics. RESULTS: Eighty-six patients (28.3%) reported at least one visit to the AED during the previous year and 75 (24.7%) twice or more. 124 patients (40.8%) had some form of mental disorder with 85 (28.0%) meeting criteria for major depressive disorder. The degree to which the patients had an understanding of their illness (illness comprehensibility) (p<0.01) along with younger age (p<0.05), additional comorbidities (p<0.05) and greater somatic symptom burden (p<0.001) was strongly associated with AED use; AED visits were expected to be reduced by 9.1% for each unit increase in illness comprehensibility. CONCLUSIONS: The way people perceive their illness influences urgent healthcare seeking behavior independent of somatic symptom burden. This finding indicates that information provision may prove effective in reducing urgent healthcare use and encourage the design of psycho-educational interventions targeting disease-related cognitions in an attempt to prevent unnecessary healthcare utilization. PMID- 26800638 TI - Psychometric properties of a caregiver illness perception measure for caries in children under 6 years old. AB - OBJECTIVE: Based on the Common-Sense Model of Self-Regulation (CSM), the Revised Illness Perception Questionnaire (IPQ-R) was developed to measure patients' perceptions of their chronic medical illness. Such a measure does not exist for dental conditions. This study describes psychometric properties of the IPQ-R for Dental (IPQ-RD) for parent/caregivers of children under 6 years of age. METHODS: Parent/caregivers (n=160) of children aged <6 years attending a pediatric dental clinic completed the IPQ-RD and a questionnaire assessing their socio demographics, dental anxiety, oral health self-efficacy, and child's preventive dental visits. Dental charts were abstracted for child's decayed, missing, filled teeth (dmft) information. The 33-item IPQ-RD was tested for internal (construct, discriminant) and external validity (concurrent, convergent, discriminant) and reliability (internal consistency). RESULTS: Confirmatory factor analysis demonstrated that the eight-factor model in accordance with the CSM framework (identity, consequences-child, consequences-caregiver, control-child, control caregiver, timeline, illness coherence, emotional representations) had good construct validity based on significant factor loadings and acceptable to excellent model fit (RMSEA=0.078, CFI=0.951). Concurrent validity was demonstrated by significant negative correlations and higher mean factor scores for five constructs for children without dental visits indicating inaccurate caregiver perception of cavities. Discriminant validity was suggested by non relationship with external measures (dental anxiety, self-efficacy). Internal consistency of six IPQ-RD constructs was excellent (Cronbach's alpha >0.74). CONCLUSION: The IPQ-RD is a valid and reliable measure to assess parent/caregivers' representation of young children's cavities with potential to be a valuable risk assessment tool for oral health behavioral research. PMID- 26800641 TI - Interest in dental implantology and preferences for implant therapy: a survey of Victorian dentists. AB - BACKGROUND: The purpose of this study was to gauge dentists' interest, knowledge and training in implantology, and to compare their treatment preferences with current literature. Subsequently, this information may be used to evaluate implantology education pathways. METHODS: A cross-sectional postal survey of 600 randomly selected dentists registered with the Dental Practice Board of Victoria was conducted. Respondents were asked about background, interest and training in implantology, and implant treatment preferences. Results were analysed according to primary practice location, decade of graduation and attendance at continuing professional development (CPD) programmes. RESULTS: One hundred and seventy-six questionnaires were included for analysis. In general, dentists rate their implant knowledge, interest and enjoyment in restoring implants favourably. No differences were found between city and country practitioners, and different graduation decades. The level of CPD significantly influenced treatment preferences. Practitioners were generally unwilling to treat patients taking bisphosphonates, or to perform grafting procedures. Most dentists provide common services to treat peri-implant conditions. Direct-to-fixture is the most popular fixture-abutment connection. CONCLUSIONS: Overall, there is a high level of implant knowledge corresponding to current evidence in the literature. Level of CPD attendance is the most important factor in dentists' willingness to provide more implant therapy options. PMID- 26800642 TI - Estimating Skin Cancer Risk: Evaluating Mobile Computer-Adaptive Testing. AB - BACKGROUND: Response burden is a major detriment to questionnaire completion rates. Computer adaptive testing may offer advantages over non-adaptive testing, including reduction of numbers of items required for precise measurement. OBJECTIVE: Our aim was to compare the efficiency of non-adaptive (NAT) and computer adaptive testing (CAT) facilitated by Partial Credit Model (PCM)-derived calibration to estimate skin cancer risk. METHODS: We used a random sample from a population-based Australian cohort study of skin cancer risk (N=43,794). All 30 items of the skin cancer risk scale were calibrated with the Rasch PCM. A total of 1000 cases generated following a normal distribution (mean [SD] 0 [1]) were simulated using three Rasch models with three fixed-item (dichotomous, rating scale, and partial credit) scenarios, respectively. We calculated the comparative efficiency and precision of CAT and NAT (shortening of questionnaire length and the count difference number ratio less than 5% using independent t tests). RESULTS: We found that use of CAT led to smaller person standard error of the estimated measure than NAT, with substantially higher efficiency but no loss of precision, reducing response burden by 48%, 66%, and 66% for dichotomous, Rating Scale Model, and PCM models, respectively. CONCLUSIONS: CAT-based administrations of the skin cancer risk scale could substantially reduce participant burden without compromising measurement precision. A mobile computer adaptive test was developed to help people efficiently assess their skin cancer risk. PMID- 26800643 TI - Interaction between left ventricular twist mechanics and arterial haemodynamics during localised, non-metabolic hyperaemia with and without blood flow restriction. AB - NEW FINDINGS: What is the central question of this study? Left ventricular (LV) twist is reduced when afterload is increased, but the meaning of this specific heart muscle response and its impact on cardiac output are not well understood. What is the main finding and its importance? This study shows that LV twist responds even when arterial haemodynamics are altered only locally, and without apparent change in metabolic (i.e. heat-induced) demand. The concurrent decline in cardiac output and LV twist during partial arterial occlusion despite the increased peripheral demand caused by heat stress suggests that LV twist may be involved in the protective sensing of heart muscle stress that can override the provision of the required cardiac output. Whether left ventricular (LV) twist and untwisting rate (LV twist mechanics) respond to localised, peripheral, non metabolic changes in arterial haemodynamics within an individual's normal afterload range is presently unknown. Furthermore, previous studies indicate that LV twist mechanics may override the provision of cardiac output, but this hypothesis has not been examined purposefully. Therefore, we acutely altered local peripheral arterial haemodynamics in 11 healthy humans (women/men n = 3/8; age 26 +/- 5 years) by bilateral arm heating (BAH). Ultrasonography was used to examine arterial haemodynamics, LV twist mechanics and the twist-to-shortening ratio (TSR). To determine the arterial function-dependent contribution of LV twist mechanics to cardiac output, partial blood flow restriction to the arms was applied during BAH (BAHBFR ). Bilateral arm heating increased arm skin temperatures [change (Delta) +6.4 +/- 0.9 degrees C, P < 0.0001] but not core temperature (Delta -0.0 +/- 0.1 degrees C, P > 0.05), concomitant to increases in brachial artery blood flow (Delta 212 +/- 77 ml, P < 0.0001), cardiac output (Delta 495 +/- 487 l min(-1) , P < 0.05), LV twist (Delta 3.0 +/- 3.5 deg, P < 0.05) and TSR (Delta 3.3 +/- 1.3, P < 0.05) but maintained carotid artery blood flow (Delta 18 +/- 147 ml, P > 0.05). Subsequently, BAHBFR reduced all parameters to preheating levels, except for TSR and heart rate, which remained at BAH levels. In conclusion, LV twist mechanics responded to local peripheral arterial haemodynamics within the normal afterload range, in part independent of TSR and heart rate. The findings suggest that LV twist mechanics may be more closely associated with intrinsic sensing of excessive pressure stress rather than being associated with the delivery of adequate cardiac output. PMID- 26800644 TI - Assessment of quality of life in patients after surgical and transcatheter aortic valve replacement. AB - OBJECTIVES: Transcatheter aortic valve implantation (TAVI) and minimally invasive aortic valve replacement (mini-thoracotomy, mini-sternotomy, MIAVR) have become an appealing alternative to conventional surgical (SAVR) treatment of severe aortic stenosis (AS) in high-risk patients. BACKGROUND: Aim of the study was to evaluate the quality of life (QoL) in patients with AS and treated with transfemoral TAVI, SAVR, mini-thoracotomy and mini-sternotomy. METHODS: One hundred and seventy-three patients with symptomatic AS were enrolled in 2011 2013. TAVI group consisted of 39 patients (22.5%), mini-sternotomy was performed in 44 patients (25.5%), mini-thoracotomy in 50 (29%), and AVR in 40 patients (23%). QoL was assessed perioperatively, 12 and 24 months after aortic valve replacement (AVR) by Minnesota Living with Heart Failure Questionnaire (MLHFQ) and EQ-5D-3L. RESULTS: Median follow-up was 583.5 (IQR: 298-736) days. Improvement of health status after procedure in comparison with pre-operative period was significantly more often reported after TAVI in perioperative period (90.3%; P = 0.004) and 12 months after procedure (100%, P = 0.02). Global MLHFQ, physical and emotional dimension score at 30-day from AVR presented significant improvement after TAVI in comparison with surgical methods (respectively: 8.3(+/ 8.6), P = 0.003; 4.1(+/-5.9), P = 0.01; 1.5(+/-2.6), P = 0.005). Total MLHFQ score was significantly lower (better outcome) in TAVI patients 1 year after procedure (4.8(+/-6.8), P = 0.004), no differences in somatic and emotional component were found. No differences were found in MLHFQ score 24 months after AVR. Data from EQ-D5-3L questionnaire demonstrated significant improvement of QoL at 30-day follow-up after TAVI in comparison with surgical methods (1.2(+/-1.7), P = 0.0008). CONCLUSIONS: TAVI improves QoL in perioperative and 12 months observation in comparison with mini-thoracotomy, mini-sternotomy and SAVR. Improvement in QoL was obtained in both generic and disease specific questionnaires. (c) 2016 Wiley Periodicals, Inc. PMID- 26800646 TI - Mixture toxicity and interactions of copper, nickel, cadmium, and zinc to barley at low effect levels: Something from nothing? AB - Metal contamination is mostly a mixture of different metals, and these multicomponent mixtures can produce significant mixture effects. The present study was set up to investigate the toxicity of multiple metal mixtures of Cu, Ni, Cd, and Zn to plants at metal doses individually causing low-level phytotoxic effects. Barley (Hordeum vulgare L.) root elongation toxicity tests were performed in resin-buffered nutrient solutions to control metal speciation. Treatments included single-metal concentrations and binary, ternary, and quaternary mixtures. Mixtures of different metals at free ion concentrations, each causing <10% inhibition of root elongation, yielded significant mixture effects, with inhibition reaching up to 50%. The independent action (IA) model predicted mixture toxicity statistically better than the concentration addition (CA) model, but some synergisms relative to the IA model were observed. These synergisms relative to IA were most pronounced in quaternary mixtures and when the dose-response curves had steep slopes. Generally, antagonistic interactions relative to the CA model were observed. Increasing solution Zn concentrations shifted metal interactions (CA based) from additive or slightly synergistic at background Zn concentrations to antagonistic at higher Zn concentrations, suggesting a protective effect of Zn. Overall, the present study shows that the CA model can be used as a conservative model to predict metal mixture toxicity to barley. Environ Toxicol Chem 2016;35:2483-2492. (c) 2016 SETAC. PMID- 26800645 TI - The 5-hydroxytryptamine4 receptor enables differentiation of informational content and encoding in the hippocampus. AB - Long-term synaptic plasticity, represented by long-term depression (LTD) and long term potentiation (LTP) comprise cellular processes that enable memory. Neuromodulators such as serotonin regulate hippocampal function, and the 5-HT4 receptor contributes to processes underlying cognition. It was previously shown that in the CA1-region, 5-HT4 -receptors regulate the frequency-response relationship of synaptic plasticity: patterned afferent stimulation that has no effect on synaptic strength (i.e., a thetam-frequency), will result in LTP or LTD, when given in the presence of a 5-HT4 -agonist, or antagonist, respectively. Here, we show that in the dentate gyrus (DG) and CA3 regions of freely behaving rats, pharmacological manipulations of 5-HT4 -receptors do not influence responses generated at thetam-frequencies, but activation of 5-HT4 -receptors prevents persistent LTD in mossy fiber (mf)-CA3, or perforant path-DG synapses. Furthermore, the regulation by 5-HT4 -receptors of LTP is subfield-specific: 5 HT4 -receptor-activation prevents mf-CA3-LTP, but does not strongly affect DG potentiation. These data suggest that 5-HT4 -receptor activation prioritises information encoding by means of LTP in the DG and CA1 regions, and suppresses persistent information storage in mf-CA3 synapses. Thus, 5-HT4 -receptors serve to shape information storage across the hippocampal circuitry and specify the nature of experience-dependent encoding. (c) 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID- 26800647 TI - One-year clinical evaluation of different types of bulk-fill composites. AB - AIM: In the present study, we evaluated the 1-year clinical performance of a conventional posterior composite resin and three bulk-fill composite resins. METHODS: Fifty patients with four class II restorations under occlusion were enrolled in the present study. A total of 200 restorations were placed in the cavity, 50 for each material (Clearfil Photo Posterior, Filtek Bulk-Fill Flowable and Filtek P60, Tetric EvoCeram Bulk-Fill, and SonicFill). One operator placed the restorations in the cavity, and 1 week later the patients were called for baseline examination. Two calibrated examiners evaluated the restorations once every 3 months for 1 year, according to United States Public Health Service criteria. The data were analyzed using SPSS. Non-parametric tests (Kruskal Wallis, Mann-Whitney U-test, and Friedman) were used for the analysis at a confidence level of 95%. RESULTS: The 1-year recall rate was 86%. All restorations showed minor modifications after 1 year. However, no statistically significant differences were detected between the materials' performance at baseline and after 1 year for all criteria (P > 0.05). CONCLUSIONS: The bulk-fill composite resin materials showed similar clinical performance when compared with a conventional posterior composite resin. Further evaluations are necessary for the long-term clinical performance of these materials. PMID- 26800648 TI - Unusual poly(3-hydroxyalkanoate) (PHA) biosynthesis behavior of Pseudomonas putida Bet001 and Delftia tsuruhatensis Bet002 isolated from palm oil mill effluent. AB - Pseudomonas putida Bet001 and Delftia tsuruhatensis Bet002, isolated from palm oil mill effluent, accumulated poly(3-hydroxyalkanoates) (PHAs) when grown on aliphatic fatty acids, sugars, and glycerol. The substrates were supplied at 20:1 C/N mole ratio. Among C-even n-alkanoic acids, myristic acid gave the highest PHA content 26 and 28 wt% in P. putida and D. tsuruhatensis, respectively. Among C odd n-alkanoic acids, undecanoic gave the highest PHA content at 40 wt% in P. putida and 46 wt% in D. tsuruhatensis on pentadecanoic acid. Sugar and glycerol gave <10 wt% of PHA content for both bacteria. Interestingly, D. tsuruhatensis accumulated both short- and medium-chain length PHA when supplied with n-alkanoic acids ranging from octanoic to lauric, sucrose, and glycerol with 3 hydroxybutyrate as the major monomer unit. In P. putida, the major hydroxyalkanoates unit was 3-hydroxyoctanoate and 3-hydroxydecanoate when grown on C-even acids. Conversely, 3-hydroxyheptanoate, 3-hydrxoynonanoate, and 3 hydroxyundecanoate were accumulated with C-odd acids. Weight-averaged molecular weight (Mw ) was in the range of 53-81 kDa and 107-415 kDa for P. putida and D. tsuruhatensis, respectively. Calorimetric analyses indicated that both bacteria synthesized semicrystalline polymer with good thermal stability with degradation temperature (Td ) ranging from 178 to 282 degrees C. PMID- 26800651 TI - Sarcoidosis following successful treatment of pemphigus vulgaris with rituximab: a rituximab-induced reaction further supporting B-cell contribution to sarcoidosis pathogenesis? AB - The anti-CD20 peripheral B-cell depleting monoclonal antibody, rituximab, has been shown to be a safe and effective treatment for refractory pemphigus vulgaris (PV), a potentially fatal autoimmune blistering disease. We report a patient who developed skin nodules and arthralgias following successful treatment of refractory PV with rituximab. Clinical, serological and histological findings were consistent with a diagnosis of sarcoidosis. The nodules promptly responded to treatment with corticosteroids, and resolved without recurrence when the medication was tapered several months later. The temporal onset of sarcoidosis following treatment with rituximab and the eventual resolution, coupled with the remarkable similarities between the B-cell immunological environment expected in our patient during the post-rituximab period and the immunological environment described in patients with idiopathic sarcoidosis, strongly implicates exposure to rituximab as the trigger for sarcoidosis development in our patient. We propose that rituximab-induced sarcoidal granulomas may be a rare adverse effect of treatment with this medication, providing further support for an important role of B cells in the pathogenesis of sarcoidosis. With better understanding of the circumstances surrounding sarcoidosis development following rituximab administration, this medication could potentially be used to induce sarcoidosis in animal research models to study the immunopathogenesis of this disease. PMID- 26800650 TI - Rice endosperm is cost-effective for the production of recombinant griffithsin with potent activity against HIV. AB - Protein microbicides containing neutralizing antibodies and antiviral lectins may help to reduce the rate of infection with human immunodeficiency virus (HIV) if it is possible to manufacture the components in large quantities at a cost affordable in HIV-endemic regions such as sub-Saharan Africa. We expressed the antiviral lectin griffithsin (GRFT), which shows potent neutralizing activity against HIV, in the endosperm of transgenic rice plants (Oryza sativa), to determine whether rice can be used to produce inexpensive GRFT as a microbicide ingredient. The yield of (OS) GRFT in the best-performing plants was 223 MUg/g dry seed weight. We also established a one-step purification protocol, achieving a recovery of 74% and a purity of 80%, which potentially could be developed into a larger-scale process to facilitate inexpensive downstream processing. (OS) GRFT bound to HIV glycans with similar efficiency to GRFT produced in Escherichia coli. Whole-cell assays using purified (OS) GRFT and infectivity assays using crude extracts of transgenic rice endosperm confirmed that both crude and pure (OS) GRFT showed potent activity against HIV and the crude extracts were not toxic towards human cell lines, suggesting they could be administered as a microbicide with only minimal processing. A freedom-to-operate analysis confirmed that GRFT produced in rice is suitable for commercial development, and an economic evaluation suggested that 1.8 kg/ha of pure GRFT could be produced from rice seeds. Our data therefore indicate that rice could be developed as an inexpensive production platform for GRFT as a microbicide component. PMID- 26800649 TI - Sex differences in cannabinoid-regulated biology: A focus on energy homeostasis. AB - Considerable strides have been made over the past 20 years in our understanding of the ligands, receptor subtypes, signal transduction mechanisms and biological actions comprising the endocannabinoid system. From the ever-expanding number of studies that have been conducted during this time, it has become increasingly clear that sex differences are the cornerstone of cannabinoid-regulated biology. Available evidence has demonstrated that these sex differences endure in the absence of gonadal steroids, and are modulated by the acute, activational effects of these hormones. This review focuses on select aspects of sexually differentiated, cannabinoid-regulated biology, with a particular emphasis on the control of energy balance. It is anticipated that it will lend impactful insight into the pervasive and diverse disparities in how males and females respond to cannabinoids--from the organismal level down to the molecular level. Additionally, it will furnish a newfound appreciation for the need to recalibrate our thinking in terms of how cannabinoids are used as therapeutic adjuvants for a broad range of clinical disorders and associated comorbidities, including body wasting and obesity. PMID- 26800652 TI - Genome-wide dissection of AP2/ERF and HSP90 gene families in five legumes and expression profiles in chickpea and pigeonpea. AB - APETALA2/ethylene response factor (AP2/ERF) and heat-shock protein 90 (HSP90) are two significant classes of transcription factor and molecular chaperone proteins which are known to be implicated under abiotic and biotic stresses. Comprehensive survey identified a total of 147 AP2/ERF genes in chickpea, 176 in pigeonpea, 131 in Medicago, 179 in common bean and 140 in Lotus, whereas the number of HSP90 genes ranged from 5 to 7 in five legumes. Sequence alignment and phylogenetic analyses distinguished AP2, ERF, DREB, RAV and soloist proteins, while HSP90 proteins segregated on the basis of their cellular localization. Deeper insights into the gene structure allowed ERF proteins to be classified into AP2s based on DNA-binding domains, intron arrangements and phylogenetic grouping. RNA-seq and quantitative real-time PCR (qRT-PCR) analyses in heat-stressed chickpea as well as Fusarium wilt (FW)- and sterility mosaic disease (SMD)-stressed pigeonpea provided insights into the modus operandi of AP2/ERF and HSP90 genes. This study identified potential candidate genes in response to heat stress in chickpea while for FW and SMD stresses in pigeonpea. For instance, two DREB genes (Ca_02170 and Ca_16631) and three HSP90 genes (Ca_23016, Ca_09743 and Ca_25602) in chickpea can be targeted as potential candidate genes. Similarly, in pigeonpea, a HSP90 gene, C.cajan_27949, was highly responsive to SMD in the resistant genotype ICPL 20096, can be recommended for further functional validation. Also, two DREB genes, C.cajan_41905 and C.cajan_41951, were identified as leads for further investigation in response to FW stress in pigeonpea. PMID- 26800653 TI - Relation between premorbid adjustment, duration of untreated psychosis and close interpersonal trauma in first-episode psychosis. AB - AIM: Interpersonal traumas are highly prevalent in patients with psychotic disorders. Trauma caused by those close to the patient might have a more profound impact than other types of trauma and may influence early life social functioning. The aim is to investigate the associations between different types of trauma, in particular close interpersonal traumas experienced before the age of 18, premorbid factors and baseline clinical characteristics in a sample of first-episode psychosis patients. METHODS: A total of 191 patients from the 'TIPS' cohort completed assessment with the Brief Betrayal Trauma Survey at their 5 years follow-up interview. RESULTS: Half of the patients reported that they had experienced interpersonal trauma and one-third reported having experienced close interpersonal trauma before the age of 18. Women reported more sexual abuse, physical attacks and emotional and physical maltreatment than men. There were significant associations between early interpersonal trauma and premorbid adjustment and duration of untreated psychosis, but no significant associations with length of education, comorbid substance use or baseline clinical symptomatology. CONCLUSIONS: Close interpersonal trauma before the age of 18 is associated with poorer premorbid adjustment and a longer duration of untreated psychosis. This may indicate that traumatic experiences delay help-seeking behaviour. PMID- 26800654 TI - 2-Methylcitric acid impairs glutamate metabolism and induces permeability transition in brain mitochondria. AB - Accumulation of 2-methylcitric acid (2MCA) is observed in methylmalonic and propionic acidemias, which are clinically characterized by severe neurological symptoms. The exact pathogenetic mechanisms of brain abnormalities in these diseases are poorly established and very little has been reported on the role of 2MCA. In the present work we found that 2MCA markedly inhibited ADP-stimulated and uncoupled respiration in mitochondria supported by glutamate, with a less significant inhibition in pyruvate plus malate respiring mitochondria. However, no alterations occurred when alpha-ketoglutarate or succinate was used as respiratory substrates, suggesting a defect on glutamate oxidative metabolism. It was also observed that 2MCA decreased ATP formation in glutamate plus malate or pyruvate plus malate-supported mitochondria. Furthermore, 2MCA inhibited glutamate dehydrogenase activity at concentrations as low as 0.5 mM. Kinetic studies revealed that this inhibitory effect was competitive in relation to glutamate. In contrast, assays of osmotic swelling in non-respiring mitochondria suggested that 2MCA did not significantly impair mitochondrial glutamate transport. Finally, 2MCA provoked a significant decrease in mitochondrial membrane potential and induced swelling in Ca(2+)-loaded mitochondria supported by different substrates. These effects were totally prevented by cyclosporine A plus ADP or ruthenium red, indicating induction of mitochondrial permeability transition. Taken together, our data strongly indicate that 2MCA behaves as a potent inhibitor of glutamate oxidation by inhibiting glutamate dehydrogenase activity and as a permeability transition inducer, disturbing mitochondrial energy homeostasis. We presume that 2MCA-induced mitochondrial deleterious effects may contribute to the pathogenesis of brain damage in patients affected by methylmalonic and propionic acidemias. We propose that brain glutamate oxidation is disturbed by 2-methylcitric acid (2MCA), which accumulates in tissues from patients with propionic and methylmalonic acidemias because of a competitive inhibition of glutamate dehydrogenase (GDH) activity. 2MCA also induced mitochondrial permeability transition (PT) and decreased ATP generation in brain mitochondria. We believe that these pathomechanisms may be involved in the neurological dysfunction of these diseases. PMID- 26800656 TI - Breakdown. PMID- 26800655 TI - Autophagy is involved in regulating the immune response of dendritic cells to influenza A (H1N1) pdm09 infection. AB - Autophagy can mediate antiviral immunity. However, it remains unknown whether autophagy regulates the immune response of dendritic cells (DCs) to influenza A (H1N1) pdm09 infection. In this study, we found that infection with the H1N1 virus induced DC autophagy in an endocytosis-dependent manner. Compared with autophagy-deficient Beclin-1(+/-) mice, we found that bone-marrow-derived DCs from wild-type mice (WT BMDCs) presented a more mature phenotype on H1N1 infection. Wild-type BMDCs secreted higher levels of interleukin-6 (IL-6), tumour necrosis factor- alpha (TNF-alpha), interferon-beta (IFN-beta), IL-12p70 and IFN gamma than did Beclin-1(+/-) BMDCs. In contrast to Beclin-1(+/-) BMDCs, H1N1 infected WT BMDCs exhibited increased activation of extracellular signal regulated kinase, Jun N-terminal kinase, p38, and nuclear factor-kappaB as well as IFN regulatory factor 7 nuclear translocation. Blockade of autophagosomal and lysosomal fusion by bafilomycin A1 decreased the co-localization of H1N1 viruses, autophagosomes and lysosomes as well as the secretion of IL-6, TNF-alpha and IFN beta in H1N1-infected BMDCs. In contrast to Beclin-1(+/-) BMDCs, H1N1-infected WT BMDCs were more efficient in inducing allogeneic CD4(+) T-cell proliferation and driving T helper type 1, 2 and 17 cell differentiation while inhibiting CD4(+) Foxp3(+) regulatory T-cell differentiation. Moreover, WT BMDCs were more efficient at cross-presenting the ovalbumin antigen to CD8(+) T cells. We consistently found that Beclin-1(+/-) BMDCs were inferior in their inhibition of H1N1 virus replication and their induction of H1N1-specific CD4(+) and CD8(+) T cell responses, which produced lower levels of IL-6, TNF-alpha and IFN-beta in vivo. Our data indicate that autophagy is important in the regulation of the DC immune response to H1N1 infection, thereby extending our understanding of host immune responses to the virus. PMID- 26800657 TI - Carbon dioxide laser ablation of basal cell carcinoma with visual guidance by reflectance confocal microscopy: a proof-of-principle pilot study. AB - BACKGROUND: Laser ablation is an alternative, nonsurgical treatment modality for low-risk basal cell carcinoma (BCC). However, lack of confirmative tumour destruction or residual tumour presence has been a limiting factor to its adoption. Reflectance confocal microscopy (RCM) provides noninvasive, cellular level resolution imaging of the skin and is capable of identifying tumour. OBJECTIVES: To evaluate the use of RCM to guide carbon dioxide (CO2 ) laser ablation of BCC, confirm destruction and correlate findings with histology. METHODS: RCM was used preablation to evaluate for features of BCC. Ablation was performed with a CO2 laser, and the response rapidly assessed using handheld RCM to evaluate for residual tumour. Confirmative pathology was used to verify confocal imaging. RESULTS: Preablation RCM imaging identified tumour with features not identified on normal, surrounding skin. Postablation, RCM documented complete removal of tumour in six cases and residual tumour in two. Histological examination identified the ablated area and confirmed clearance of tumour in the six aforementioned cases and corroborated confocal findings for residual tumour in the other two cases. CONCLUSIONS: We report successful treatment of superficial and nodular BCC using CO2 laser ablation augmented by RCM imaging for preablation guidance and verification of tumour removal postablation. Akin to complete circumferential and deep margin control techniques, using RCM helps to map peripheral and deep BCC margins to hone in on areas exhibiting persistent tumour after ablation. CO2 laser ablation visually guided by RCM can help circumvent previously cited limiting factors of laser ablation for tumour destruction by providing cellular-level resolution imaging of tumour and margin assessment in between each laser pass and postablation. PMID- 26800658 TI - The effect of pedunculopontine nucleus deep brain stimulation on postural sway and vestibular perception. AB - BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) reduces the number of falls in patients with Parkinson's disease (PD). It was hypothesized that enhanced sensory processing contributes to this PPN-mediated gait improvement. METHODS: Four PD patients (and eight matched controls) with implanted bilateral PPN and subthalamic nucleus DBS electrodes were assessed on postural (with/without vision) and vestibular perceptual threshold tasks. RESULTS: Pedunculopontine nucleus ON stimulation (compared to OFF) lowered vestibular perceptual thresholds but there was a disproportionate increase in the normal sway increase on going from light to dark. CONCLUSIONS: The disproportionate increased sway with PPN stimulation in the dark may paradoxically improve balance function since mechanoreceptor signals rapidly adapt to continuous pressure stimulation from postural akinesia. Additionally, the PPN-mediated vestibular signal enhancement also improves the monitoring of postural sway. Overall, PPN stimulation may improve sensory feedback and hence balance performance. PMID- 26800659 TI - Differential alterations of resting-state functional connectivity in generalized anxiety disorder and panic disorder. AB - Generalized anxiety disorder (GAD) and panic disorder (PD) are most common anxiety disorders with high lifetime prevalence while the pathophysiology and disease-specific alterations still remain largely unclear. Few studies have taken a whole-brain perspective in the functional connectivity (FC) analysis of these two disorders in resting state. It limits the ability to identify regionally and psychopathologically specific network abnormalities with their subsequent use as diagnostic marker and novel treatment strategy. The whole brain FC using a novel FC metric was compared, that is, scaled correlation, which they demonstrated to be a reliable FC statistics, but have higher statistical power in two-sample t test of whole brain FC analysis. About 21 GAD and 18 PD patients were compared with 22 matched control subjects during resting-state, respectively. It was found that GAD patients demonstrated increased FC between hippocampus/parahippocampus and fusiform gyrus among the most significantly changed FC, while PD was mainly associated with greater FC between somatosensory cortex and thalamus. Besides such regional specificity, it was observed that psychopathological specificity in that the disrupted FC pattern in PD and GAD correlated with their respective symptom severity. The findings suggested that the increased FC between hippocampus/parahippocampus and fusiform gyrus in GAD were mainly associated with a fear generalization related neural circuit, while the greater FC between somatosensory cortex and thalamus in PD were more likely linked to interoceptive processing. Due to the observed regional and psychopathological specificity, their findings bear important clinical implications for the potential treatment strategy. PMID- 26800660 TI - PTSD in ICD-10 and proposed ICD-11 in elderly with childhood trauma: prevalence, factor structure, and symptom profiles. AB - BACKGROUND: The proposal for ICD-11 postulates major changes for posttraumatic stress disorder (PTSD) diagnosis, which needs investigation in different samples. AIMS: To investigate differences of PTSD prevalence and diagnostic agreement between ICD-10 and ICD-11, factor structure of proposed ICD-11 PTSD, and diagnostic value of PTSD symptom severity classes. METHOD: Confirmatory factor analysis and latent profile analysis were used on data of elderly survivors of childhood trauma (>60 years, N=399). RESULTS: PTSD rates differed significantly between ICD-10 (15.0%) and ICD-11 (10.3%, z=2.02, p=0.04). Unlike previous research, a one-factor solution of ICD-11 PTSD had the best fit in this sample. High symptom profiles were associated with PTSD in ICD-11. CONCLUSIONS: ICD-11 concentrates on PTSD's core symptoms and furthers clinical utility. Questions remain regarding the tendency of ICD-11 to diagnose mainly cases with severe symptoms and the influence of trauma type and participant age on the factor structure. PMID- 26800661 TI - Comparative study of self-expanding metal stent and intraluminal radioactive stent for inoperable esophageal squamous cell carcinoma. AB - BACKGROUND: We compared the effectiveness of self-expanding metal stent alone vs. radioactive stent embedded with 125I seeds implantation insertion in patients of inoperable esophageal squamous cell cancer combined with malignant esophageal stenosis. METHODS: We studied two groups of patients with stenosis attribute to inoperable esophageal squamous cell carcinoma. Group A had placed self-expanding metal stent alone insertion; group B encountered radioactive stent embedded with 125I seeds. Patients were followed up by monthly home visits or telephone interview. Survival time was analyzed with Kaplan-Meier analysis. Log rank test was used to analyze factors of survival time for all significant differences. RESULTS: There was no significant difference between the two groups of all baseline characteristics. There was no statistical difference in complications including massive hematemesis, pain more than 1 month, stent migration, and restenosis. Survival time and causes of death such as tumor metastasis, massive hemorrhage, non-tumor-related factors, and restenosis were comparable between the two groups (P>0.05). The medical costs were significantly less in group A than those in group B (P<0.01). CONCLUSIONS: Radioactive stent embedded with (125)I seeds was not significant in improving survival rate, but showed to increase hospitalization costs compared to self-expandable metal stent alone in treating inoperable esophageal squamous cell carcinoma stricture. PMID- 26800662 TI - Role of cardiovascular magnetic resonance in the guidelines of the European Society of Cardiology. AB - BACKGROUND: Despite common enthusiasm for cardiovascular magnetic resonance (CMR), its application in Europe is quite diverse. Restrictions are attributed to a number of factors, like limited access, deficits in training, and incomplete reimbursement. Aim of this study is to perform a systematic summary of the representation of CMR in the guidelines of the European Society of Cardiology (ESC). METHODS: Twenty-nine ESC guidelines were screened for the terms "magnetic", "MRI", "CMR", "MR" and "imaging". As 3 topics were published twice (endocarditis, pulmonary hypertension, NSTEMI), 26 guidelines were finally included. MRI in the context of non-cardiovascular examinations was not recognized. The main CMR-related conclusions and, if available, the level of evidence and the class of recommendation were extracted. RESULTS: Fourteen of the 26 guidelines (53.8%) contain specific recommendations regarding the use of CMR. Nine guidelines (34.6%) mention CMR in the text, and 3 (11.5%) do not mention CMR. The 14 guidelines with recommendations regarding the use of CMR contain 39 class-I recommendations, 12 class-IIa recommendations, 10 class-IIb recommendations and 2 class-III recommendations. Most of the recommendations have evidence level C (41/63; 65.1%), followed by level B (16/63; 25.4%) and level A (6/63; 9.5%). The four guidelines, which absolutely contained most recommendations for CMR, were stable coronary artery disease (n = 14), aortic diseases (n = 9), HCM (n = 7) and myocardial revascularization (n = 7). CONCLUSIONS: CMR is represented in the majority of the ESC guidelines. They contain many recommendations in favour of the use of CMR in specific scenarios. Issues regarding access, training and reimbursement have to be solved to offer CMR to patients in accordance with the ESC guidelines. PMID- 26800663 TI - [Translational research in pediatric rheumatology. Current research approaches to the innate immune system]. AB - Translational research aims at closely linking basic research and clinical observations so that important mechanistic insights identified in one field should trigger progress in the other. Particularly in the field of pediatric rheumatology this approach has significantly improved the understanding and therapy of several diseases in recent years. One focus of our research in this respect is on the structure, release mechanisms and function of damage associated molecular patterns (DAMP), particularly S100 proteins. Due to their huge potential as inflammation biomarkers for more specific diagnostics these proteins are of particular clinical interest. Overactivated cells of the innate immune system play a crucial role in the development of rheumatic diseases. Innate mechanisms, such as the generation of neutrophil extracellular traps (NETosis) were linked to the pathogenesis of inflammatory diseases, such as systemic lupus erythematosus and rheumatoid arthritis. Furthermore, it became increasingly more evident that various excessive sterile inflammatory mechanisms and reactions significantly contribute to an activation of adaptive immune responses and thus to the development of autoimmunity. Studying such potentially DAMP-dependent pathways at the interface between innate and adaptive immunity can provide a better understanding of autoinflammatory conditions in pediatric rheumatology and to identify novel targets for optimization of therapy. PMID- 26800664 TI - Association of cytokine gene polymorphisms (IL-6, IL-12B, IL-18) with Behcet's disease : A meta-analysis. AB - PURPOSE: This study aims to investigate the association of cytokine gene polymorphisms with the risk of Behcet's disease (BD) via comprehensive meta analysis. METHODS: The Embase and PubMed databases covering the period from the earliest possible year to May 2015 were searched. A total of 13 eligible articles including 2,065 BD patients and 1,559 controls were recruited. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the associations. Potential publication bias was evaluated using Egger's linear regression test. RESULTS: Meta-analysis indicated associations between IL-6 rs1800795, IL-12B rs3212227, and IL-18 rs1946518 in all study subjects: IL-18 rs1946518 in the dominant model (IL-18 rs1946518: OR = 0.48, 95 % CI: 0.34-0.70, P = 0.000) and the homozygote model (IL-18 rs1946518: OR = 0.40, 95 % CI: 0.25 0.65, P = 0.000); and IL-6 rs1800795 and IL-12B rs3212227 in the dominant model (IL-6 rs1800795: OR = 0.53, 95 % CI: 0.39-0.72, P = 0.000; IL-12B rs3212227: OR = 1.26, 95 % CI: 1.06-1.48, P = 0.007; IL-18 rs1946518: OR = 0.46, 95 % CI: 0.33 0.65, P = 0.000). No significant evidence for associations of IL-18 rs187238 polymorphisms with BD susceptibility was detected. CONCLUSION: In summary, this meta-analysis finds that IL-6 rs1800795 and IL-18 rs1946518 polymorphisms decrease the risk of BD. However, IL-12B rs3212227 increases BD susceptibility. Further large-scale investigation of this association is necessary. PMID- 26800665 TI - Micromonospora soli sp. nov., isolated from rice rhizosphere soil. AB - An actinomycete strain SL3-70(T) was isolated from a rice field and characterised using a polyphasic approach. The morphological and chemotaxonomical characteristics of strain SL3-70(T) indicate that it belongs to the genus Micromonospora. The phylogenetic analysis of the nearly complete 16S rRNA gene sequence revealed that strain SL3-70(T) is a member of the genus Micromonospora, and is closely related to Micromonospora echinaurantica DSM 43904(T) (99.1 % 16S rRNA gene sequence similarity) and Micromonospora kangleipakensis MBRL 34(T) (98.8 %). DNA-DNA relatedness between strain SL3-70(T) and its relatives ranged from 21.2 % +/- 0.6 to 38.7 % +/- 0.4. The results obtained from our study indicate that strain SL3-70(T) represents a novel species of the genus Micromonospora, for which the name Micromonospora soli sp. nov. is proposed. The type strain is SL3-70(T) (=BCC 67268(T); =NBRC 110009(T)). PMID- 26800666 TI - Ascidiimonas aurantiaca gen. nov., sp. nov., a member of Flavobacteriaceae isolated from a sea squirt. AB - A Gram-stain negative, strictly aerobic, chemoheterotrophic, tangerine orange pigmented, curved-rod shaped bacterium, designated N5DA8-2C(T), was isolated from a sea squirt by use of a bait-streaked agar technique. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that the novel marine strain is affiliated with the family Flavobacteriaceae of the phylum Bacteroidetes and that it shared high (92.6 %) sequence similarity with Frondibacter aureus A5Q-67(T). The strain could be differentiated phenotypically from the related members of the family Flavobacteriaceae. The major fatty acids of strain N5DA8-2C(T) were iso C15:1 G, iso-C17:0 3-OH, iso-C15:0 and C16:1 omega7c and/or C16:1 omega6c. A polar lipid profile was present consisting of phosphatidylethanolamine and three unidentified amino lipids. The DNA G+C content of the strain was determined to be 41 mol% and the major respiratory quinone was identified as menaquinone 6 (MK-6). From the distinct phylogenetic position and combination of genotypic and phenotypic characteristics, the strain is considered to represent a novel genus in the family Flavobacteriaceae, for which the name Ascidiimonas aurantiaca gen. nov., sp. nov. is proposed. The type strain of A. aurantiaca gen. nov., sp. nov. is N5DA8-2C(T) (= KCTC 32992(T) = NBRC 110020(T)). PMID- 26800667 TI - A sinogram denoising algorithm for low-dose computed tomography. AB - BACKGROUND: From the viewpoint of the patients' health, reducing the radiation dose in computed tomography (CT) is highly desirable. However, projection measurements acquired under low-dose conditions will contain much noise. Therefore, reconstruction of high-quality images from low-dose scans requires effective denoising of the projection measurements. METHODS: We propose a denoising algorithm that is based on maximizing the data likelihood and sparsity in the gradient domain. For Poisson noise, this formulation automatically leads to a locally adaptive denoising scheme. Because the resulting optimization problem is hard to solve and may also lead to artifacts, we suggest an explicitly local denoising method by adapting an existing algorithm for normally-distributed noise. We apply the proposed method on sets of simulated and real cone-beam projections and compare its performance with two other algorithms. RESULTS: The proposed algorithm effectively suppresses the noise in simulated and real CT projections. Denoising of the projections with the proposed algorithm leads to a substantial improvement of the reconstructed image in terms of noise level, spatial resolution, and visual quality. CONCLUSION: The proposed algorithm can suppress very strong quantum noise in CT projections. Therefore, it can be used as an effective tool in low-dose CT. PMID- 26800668 TI - In vitro salivary pellicles from adults and children have different protective effects against erosion. AB - OBJECTIVES: We aimed at analyzing the protective effects of salivary pellicles, formed with saliva from adults or children, on enamel from permanent or deciduous teeth. MATERIALS AND METHODS: Ninety human enamel specimens (45 permanent premolars and 45 deciduous canines) were ground, and the outer 200 MUm of enamel was removed. We divided the teeth into three further subgroups: no salivary pellicle (control), adult salivary pellicle (AP), and child salivary pellicle (CP). We collected stimulated saliva from adults and children and placed 160 MUl of either saliva on enamel specimens from AP and CP, respectively. Control specimens received no saliva. Specimens were stored at 37 degrees C for 2 h and then submitted to an erosive challenge (10 mL; 1 % citric acid; pH 3.6; 25 degrees C, 1 min). Pellicle formation and erosion was repeated for a total of 4 cycles. After every cycle, relative surface reflection intensity (rSRI) and surface microhardness (rSMH) were calculated. RESULTS: On permanent enamel, AP presented significantly better protective effects, with less rSMH loss (p < 0.001) and less rSRI loss (p < 0.001). On deciduous enamel, CP presented significantly better protective effects than AP and control (p < 0.05), for both measured parameters. CONCLUSION: We conclude that pellicles from adults and children promote different erosion protective effects, where adult pellicle provides better protection for permanent enamel, and child pellicle promotes better protection on deciduous enamel. CLINICAL RELEVANCE: The present results provide a better understanding toward the protective effect of salivary pellicle against dental erosion and brings light to one more factor involved in the erosion of deciduous teeth. PMID- 26800669 TI - Influence of conventional and digital intraoral impressions on the fit of CAD/CAM fabricated all-ceramic crowns. AB - OBJECTIVES: To compare the fit of all-ceramic crowns fabricated from conventional silicone impressions with the fit of all-ceramic crowns fabricated from intraoral digital impressions. METHODS: Thirty patients with 30 posterior teeth with a prosthetic demand were selected. Zirconia-based ceramic crowns were made using an intraoral digital impression system (Ultrafast Optical Sectioning technology) (digital group, D) and 2-step silicone impression technique (conventional group, C). To replicate the interface between the crown and the preparation, each crown was cemented on its corresponding clinical preparation using ultra-flow silicone. Each crown was embedded in resin to stabilize the registered interface. Specimens were sectioned in buccolingual orientation, and internal misfit was measured at different areas using stereomicroscopy (*40). Data was analysed using Student's t test and Mann-Whitney test (alpha = 0.05). RESULTS: No statistically significant differences were found (P > 0.05) between two groups. The mean internal misfit and mean marginal misfit were 170.9 MUm (SD = 119.4)/106.6 MUm (SD = 69.6) for group D and 185.4 MUm (SD = 112.1)/119.9 MUm (SD = 59.9) for group C. CONCLUSION: Ceramic crowns fabricated using an intraoral scanner are comparable to elastomer conventional impressions in terms of their marginal and internal fits. The mean marginal fit in both groups was within the limits of clinical acceptability. CLINICAL SIGNIFICANCE: Impressions based on Ultrafast Optical Sectioning technology can be used for manufacturing ceramic crowns in a normal workflow, with the same results as silicone conventional impressions. PMID- 26800670 TI - Xuhuaishuia manganoxidans gen. nov., sp. nov., a manganese-oxidizing bacterium isolated from deep-sea sediments from the Pacific Polymetallic Nodule Province. AB - A Gram-stain-negative, strictly aerobic, non-motile, rod-shaped, manganese oxidizing bacterial strain, designated DY6-4T, was isolated from the surface sediment of the Pacific Clarion-Clipperton Fracture Zone. Phylogenetic analysis, based on 16S rRNA gene sequences, indicated that strain DY6-4T formed a lineage within the family Rhodobacteraceae and was distinct from the most closely related genera Sulfitobacter, Aliiroseovarius and Loktanella (94.0-96.0 %, 93.4-96.0 % and 91.9-95.9 % 16S rRNA gene sequence similarity, repectively). Optimal growth occurred in the presence of 1 % (w/v) NaCl, at pH 7.0 and at 28 degrees C. Strain DY6-4T contained ubiquinone-10 (Q-10) as the major ubiquinone, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine and one unidentified aminolipid as the predominant polar lipids, C18 : 1omega7c and summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) as the main fatty acids (>10 % of the total). The DNA G+C content of strain DY6-4T was 66.6 mol%. On the basis of the polyphasic analyses, strain DY6-4T is considered to represent a novel species of a novel genus in the Roseobacter clade of the family Rhodobacteraceae, for which the name Xuhuaishuia manganoxidans gen. nov., sp. nov. is proposed. The type strain is DY6-4T ( = KCTC 42421T = MCCC 1K00502T). PMID- 26800672 TI - An analysis of global youth tobacco survey for developing a comprehensive national smoking policy in Timor-Leste. AB - BACKGROUND: Smoking is a global public health concern. Timor-Leste is facing a rapidly growing epidemic of tobacco use. The trend of smoking in Timor-Leste seems to be increasing and the magnitude of the problem affects people who smoke before reaching adulthood. One of the factors implicated in the continuously rising trend of smoking among young people in Timor-Leste is clearly due to unavailability of restrictive laws and regulations. Therefore, our study sought to analyze available dataset from the Global Youth Tobacco Survey (GYTS) for developing a comprehensive national smoking policy in order to lower smoking risks among young people in Timor-Leste. METHODS: We conducted a secondary analysis of the 2009 GYTS in Timor-Leste. The 2009 GYTS assessed 1657 in-school students aged 13-15 years for current smoking prevalence and determinants of tobacco use. We used IBM SPSS version 21 software to analyze the data. Frequency analyses were computed to identify demographic characteristics of study participants. Bivariate logistic regression analysis was performed to examine the association between each demographic characteristic as well as each independent variable and the outcome of being current smokers. RESULTS: Out of 1657 in-school students, 51 % were of ages less than 15; 53 % were girls; and 45 % were in grade 2. Prevalence of current cigarette smoking was found to be 51 %. The prevalence of current smoking among in-school students increased with ages (from 46 % in less than 15 to 57 % in 15 plus). Boys were more likely to be smokers than girls (59 % versus 28 %). Significant factors positively associated with current smoking included parental smoking; closed-peer smoking; number of days people smoked in the house; having family discussion about harmful effects of smoking; being smoking in areas such as school, public places and home; and having seen cigarette advertisements on billboard. CONCLUSION: Timor-Leste has higher prevalence of cigarette smoking among minors, especially among boys. Our analysis provides evidence-based information for developing comprehensive tobacco control programs - both education and policy interventions to reduce smoking rate among young people in Timor-Leste. PMID- 26800671 TI - Identification of the genes involved in odorant reception and detection in the palm weevil Rhynchophorus ferrugineus, an important quarantine pest, by antennal transcriptome analysis. AB - BACKGROUND: The Red Palm Weevil (RPW) Rhynchophorus ferrugineus (Oliver) is one of the most damaging invasive insect species in the world. This weevil is highly specialized to thrive in adverse desert climates, and it causes major economic losses due to its effects on palm trees around the world. RPWs locate palm trees by means of plant volatile cues and use an aggregation pheromone to coordinate a mass-attack. Here we report on the high throughput sequencing of the RPW antennal transcriptome and present a description of the highly expressed chemosensory gene families. RESULTS: Deep sequencing and assembly of the RPW antennal transcriptome yielded 35,667 transcripts with an average length of 857 bp and identified a large number of highly expressed transcripts of odorant binding proteins (OBPs), chemosensory proteins (CSPs), odorant receptors/co-receptors (ORs/Orcos), sensory neuron membrane proteins (SNMPs), gustatory receptors (GRs) and ionotropic receptors (IRs). In total, 38 OBPs, 12 CSPs, 76 ORs, 1 Orco, 6 SNMPs, 15 GRs and 10 IRs were annotated in the R. ferrugineus antennal transcriptome. A comparative transcriptome analysis with the bark beetle showed that 25% of the blast hits were unique to R. ferrugineus, indicating a higher, more complete transcript coverage for R. ferrugineus. We categorized the RPW ORs into seven subfamilies of coleopteran ORs and predicted two new subfamilies of ORs. The OR protein sequences were compared with those of the flour beetle, the cerambycid beetle and the bark beetle, and we identified coleopteran-specific, highly conserved ORs as well as unique ORs that are putatively involved in RPW aggregation pheromone detection. We identified 26 Minus-C OBPs and 8 Plus-C OBPs and grouped R. ferrugineus OBPs into different OBP-subfamilies according to phylogeny, which indicated significant species-specific expansion and divergence in R. ferrugineus. We also identified a diverse family of CSP proteins, as well as a coleopteran-specific CSP lineage that diverged from Diptera and Lepidoptera. We identified several extremely diverged IR orthologues as well as highly conserved insect IR co-receptor orthologous transcripts in R. ferrugineus. Notably, GR orthologous transcripts for CO2-sensing and sweet tastants were identified in R. ferrugineus, and we found a great diversity of GRs within the coleopteran family. With respect to SNMP-1 and SNMP-2 orthologous transcripts, one SNMP-1 orthologue was found to be strikingly highly expressed in the R. ferrugineus antennal transcriptome. CONCLUSION: Our study presents the first comprehensive catalogue of olfactory gene families involved in pheromone and general odorant detection in R. ferrugineus, which are potential novel targets for pest control strategies. PMID- 26800673 TI - A hybrid approach for quantifying aortic valve stenosis using impedance cardiography and echocardiography. AB - BACKGROUND: Impedance cardiography (IC) is a noninvasive modality that utilizes changes in impedance across the thorax to assess hemodynamic parameters, including stroke volume (SV). This study compared aortic valve area (AVA) as assessed by a hybrid approach of transthoracic echocardiography (TTE) and impedance cardiography (IC) to AVA determined at cardiac catheterization using the Gorlin equation. METHODS: A total of 30 patients with moderate to severe aortic stenosis underwent AVA measurement using two different approaches: using the continuity equation (CE) in a hybrid method combining IC and TTE (AVA = stroke by volume impedance cardiography/trans-aortic-VTI) and using the Gorlin equation. Patient age ranged from 37 to 82 years (mean 48); there were 21 men and 9 women. Twenty-five patients were in sinus rhythm, and five had atrial fibrillation. RESULTS: There was no statistically significant difference for the mean AVA between the two methods (0.7 +/- 0.24 cm(2) using the Gorlin equation versus 0.7 +/- 0.23 cm(2) using the hybrid approach, p = 0.17; r = 0.76, p < 0.001). The mean difference was 0.004 cm(2), and the limits of agreement were 0.33 to 0.37. CONCLUSION: The hybrid method using impedance cardiography and TTE is a reasonable, clinically applicable approach to evaluate AVA and has significant correlation to invasive measurement using the Gorlin equation. PMID- 26800674 TI - Highlighting Uncertainty and Recommendations for Improvement of Black Carbon Biomass Fuel-Based Emission Inventories in the Indo-Gangetic Plain Region. AB - Black carbon (BC) is a major contributor to hydrological cycle change and glacial retreat within the Indo-Gangetic Plain (IGP) and surrounding region. However, significant variability exists for estimates of BC regional concentration. Existing inventories within the IGP suffer from limited representation of rural sources, reliance on idealized point source estimates (e.g., utilization of emission factors or fuel-use estimates for cooking along with demographic information), and difficulty in distinguishing sources. Inventory development utilizes two approaches, termed top down and bottom up, which rely on various sources including transport models, emission factors, and remote sensing applications. Large discrepancies exist for BC source attribution throughout the IGP depending on the approach utilized. Cooking with biomass fuels, a major contributor to BC production has great source apportionment variability. Areas requiring attention tied to research of cookstove and biomass fuel use that have been recognized to improve emission inventory estimates include emission factors, particulate matter speciation, and better quantification of regional/economic sectors. However, limited attention has been given towards understanding ambient small-scale spatial variation of BC between cooking and non-cooking periods in low-resource environments. Understanding the indoor to outdoor relationship of BC emissions due to cooking at a local level is a top priority to improve emission inventories as many health and climate applications rely upon utilization of accurate emission inventories. PMID- 26800675 TI - Components of Population Vulnerability and Their Relationship With Climate Sensitive Health Threats. AB - Climate change is increasingly being framed as risks that will impact the poorest and most vulnerable communities among us. This has led to more efforts to estimate climate change risks across populations and in the context of human health and health equity. We describe the public health dimensions of climate vulnerability-exposure, population sensitivity, and adaptive capacity-and explore how these dimensions can modify population health impacts and their distribution. An overview of health disparities associated with specific climate risks is presented, and we offer potential solutions grounded in equitable urban development and improved characterization of climate vulnerabilities. PMID- 26800676 TI - A comparison of tacrolimus and cyclosporine combined with methotrexate for graft versus-host disease prophylaxis, stratified by stem cell source: a retrospective nationwide survey. AB - This nationwide, retrospective study compared the efficacy of cyclosporine and tacrolimus with methotrexate (CsA/MTX and TAC/MTX) for acute graft-versus-host disease (aGVHD) prevention and transplant-related outcomes. Data were obtained from the Transplant Registry Unified Management Program of the Japan Society for Hematopoietic Cell Transplantation for >= 16-year-old leukemia patients who received CsA/MTX or TAC/MTX after bone marrow transplantation and peripheral blood stem cell transplantation from serological HLA-matched related donors (MRD), HLA 8/8 allele-matched, or one allele-mismatched unrelated bone marrow (UBM), or 0-2 antigen-mismatched unrelated cord blood (UCB) transplantation between January 2005 and December 2009. Separate analyses were performed for each cohort. Adjusted multivariate analyses indicated that in the MRD (n = 1524) and the UBM (n = 1466) cohorts, TAC/MTX significantly reduced grade II-IV aGVHD risk (HR 0.58, P = 0.006 and HR 0.77, P = 0.015, respectively) without affecting the other transplant-related outcomes. In the UCB cohort (n = 925), TAC/MTX significantly reduced the risk of non-relapse mortality (HR 0.63, P = 0.027) and chronic GVHD (HR 0.60, P = 0.02) without significant effects on grade II-IV aGVHD (HR 0.83, P = 0.21). Our results may provide the most up-to-date data regarding GVHD prevention in Japan. PMID- 26800677 TI - Shortened first-line TB treatment in Brazil: potential cost savings for patients and health services. AB - BACKGROUND: Shortened treatment regimens for tuberculosis are under development to improve treatment outcomes and reduce costs. We estimated potential savings from a societal perspective in Brazil following the introduction of a hypothetical four-month regimen for tuberculosis treatment. METHODS: Data were gathered in ten randomly selected health facilities in Rio de Janeiro. Health service costs were estimated using an ingredient approach. Patient costs were estimated from a questionnaire administered to 126 patients. Costs per visits and per case treated were analysed according to the type of therapy: self administered treatment (SAT), community- and facility-directly observed treatment (community-DOT, facility-DOT). RESULTS: During the last 2 months of treatment, the largest savings could be expected for community-DOT; on average USD 17,351 18,203 and USD 43,660-45,856 (bottom-up and top-down estimates) per clinic. Savings to patients could also be expected as the median (interquartile range) patient-related costs during the two last months were USD 108 (13-291), USD 93 (36-239) and USD 11 (7-126), respectively for SAT, facility-DOT and community DOT. CONCLUSION: Introducing a four-month regimen may result in significant cost savings for both the health service and patients, especially the poorest. In particular, a community-DOT strategy, including treatment at home, could maximise health services savings while limiting patient costs. Our cost estimates are likely to be conservative because a 4-month regimen could hypothetically increase the proportion of patients cured by reducing the number of patients defaulting and we did not include the possible cost benefits from the subsequent prevention of costs due to downstream transmission averted and rapid clinical improvement with less side effects in the last two months. PMID- 26800678 TI - [Classification of malignant lymphomas. Current situation]. AB - BACKGROUND: The World Health Organization (WHO) is planning an update of the WHO classification of malignant lymphomas. OBJECTIVE: To present new findings concerning the diagnostics and subclassification of malignant lymphomas. MATERIAL AND METHODS: A selective literature search ( http://www.ncbi.nlm.nih.gov ) was carried out and combined with the practical experiences of the authors in clinicopathological diagnostics. RESULTS: In recent years an increasing number of early lesions of malignant lymphomas have been described but the potential malignancy of these lesions is at least for some entities still uncertain. Newly defined entities have been described within the group of T-cell lymphomas and prognostic subgroups have been identified in the heterogeneous group of diffuse large B-cell lymphomas. Detection of mutations facilitates the differential diagnostics of morphologically similar diseases and can be an important component of the diagnostics. CONCLUSION: Recent scientific insights are being included more and more into the diagnostics of lymphomas. The update of the WHO classification is a consequence of these developments. PMID- 26800679 TI - In in vivo evaluation of the anti-inflammatory and analgesic activities of compound Muniziqi granule in experimental animal models. AB - BACKGROUND: Compound Muniziqi granule (MNZQ), a traditional Uighur medicinal preparation, comprises 13 species of medicinal plants. MNZQ is traditionally used for regulating body immunity, modulating inflammation and pain, detoxification, and inhibiting tumor growth. This study aims to scientifically evaluate the anti inflammatory and analgesic activities of MNZQ, support its clinical use and further research with scientific evidence. METHODS: The analgesic activity of MNZQ was evaluated using hot plate test and acetic acid-induced abdominal writhing test. Acute inflammation was evaluated using xylene-induced ear edema and carrageenan-induced paw edema models, while chronic inflammation was evaluated using cotton pellet-induced granuloma model. RESULTS: MNZQ exerted analgesic activities with a significant dose-dependent increase in latency in the hot plate test. The percentage inhibition suggested that MNZQ exhibited analgesic activities in the central nervous system. Meanwhile, MNZQ at 0.8, 2.4, and 7.2 g/kg strongly inhibited the acetic acid-induced writhing response by 25.22% (p < 0.01), 44.60% (p < 0.001), and 49.41% (p < 0.001), respectively. MNZQ also exerted analgesic activities in the peripheral nervous system. Moreover, MNZQ was demonstrated a significant anti-inflammatory effect against xylene-induced edema in a dose-dependent manner. The percentage inhibition was 22.24% (p < 0.01) at the highest dosage of 7.2 g/kg. MNZQ at 1.62 and 4.86 g/kg significantly reduced carrageenan-induced rat hind paw edema by 82.43% and 84.32% (p < 0.001), respectively, 1 h after injecting carrageenan, and the inhibitory effect lasted for 5 h. MNZQ also exerted a significant anti-inflammatory effect against cotton pellet-induced granuloma formation. MNZQ at 1.62 and 4.86 g/kg could inhibit granuloma formation by 17.07% and 17.60%, respectively, whereas the percentage inhibition of diclofenac was 33.12%. CONCLUSIONS: The results obtained suggest that MNZQ possesses potential anti-inflammatory and analgesic activities. This study provides a scientific basis for the use of MNZQ in alleviating pain and treating inflammatory disorders. PMID- 26800680 TI - Characterization of a cold-active esterase from Serratia sp. and improvement of thermostability by directed evolution. AB - BACKGROUND: In recent years, cold-active esterases have received increased attention due to their attractive properties for some industrial applications such as high catalytic activity at low temperatures. RESULTS: An esterase encoding gene (estS, 909 bp) from Serratia sp. was identified, cloned and expressed in Escherichia coli DE3 (BL21). The estS encoded a protein (EstS) of 302 amino acids with a predicted molecular weight of 32.5 kDa. It showed the highest activity at 10 degrees C and pH 8.5. EstS was cold active and retained ~92 % of its original activity at 0 degrees C. Thermal inactivation analysis showed that the T1/2 value of EstS was 50 min at 50 degrees C (residual activity 41.23 %) after 1 h incubation. EstS is also quite stable in high salt conditions and displayed better catalytic activity in the presence of 4 M NaCl. To improve the thermo-stability of EstS, variants of estS gene were created by error-prone PCR. A mutant 1-D5 (A43V, R116W, D147N) that showed higher thermo-stability than its wild type predecessor was selected. 1-D5 showed enhanced T1/2 of 70 min at 50 degrees C and retained 63.29 % of activity after incubation at 50 degrees C for 60 min, which were about 22 % higher than the wild type (WT). CD spectrum showed that the secondary structure of WT and 1-D5 are more or less similar, but an increase in beta-sheets was recorded, which enhanced the thermostability of mutant protein. CONCLUSION: EstS was a novel cold-active and salt-tolerant esterase and half-life of mutant 1-D5 was enhanced by 1.4 times compared with WT. The features of EstS are interesting and can be exploited for commercial applications. The results have also provided useful information about the structure and function of Est protein. PMID- 26800681 TI - Risk Factors and Comorbidities in Chronic Rhinosinusitis. AB - Chronic rhinosinusitis (CRS) is a heterogeneous disorder that creates a significant burden on the healthcare system. It is caused by a combination of inflammatory, environmental, and host factors; however, the precise mechanism of how each factor leads to CRS continues to be a source of debate. Previous data regarding this topic is often inconsistent or of lower quality. In this article, we review the recent literature on the risk factors and comorbidities in CRS. Large population-based studies have helped establish smoking as a significant risk factor for CRS. The focus has now shifted towards smoking and its effect on long-term outcomes after endoscopic sinus surgery (ESS). Ciliary dyskinesia, both primary and secondary, can affect both the sinonasal cavity and lower airways simultaneously by decreasing the beat frequency of cilia and inducing mucostasis. The effects of secondary dyskinesia may be reversible and there is some evidence to suggest the use of topical mucolytics in patients with CRS. Allergy and variants of sinonasal anatomy have been hypothesized to increase the risk of developing CRS by inducing chronic inflammation and obstructing the sinus ostia. Nevertheless, emerging data regarding these topics continue to produce inconclusive results. Inflammation of the upper and lower airways can occur simultaneously as seen in patients with asthma and aspirin sensitivity. The connection between these pro-inflammatory disease states has been known for many years. Newer evidence include large population-based studies and studies that correlate objective tests, such as computer tomography scans to pulmonary function tests. However, the treatment of CRS and its effects on obstructive airway disease continues to be a topic of debate. More large prospective studies are needed in order to continue refining our knowledge of the disease processes in CRS. PMID- 26800682 TI - Evidence and knowledge gaps on the disease burden in sexual and gender minorities: a review of systematic reviews. AB - Sexual and gender minorities (SGM) include individuals with a wide range of sexual orientations, physical characteristics, and gender identities and expressions. Data suggest that people in this group face a significant and poorly understood set of additional health risks and bear a higher burden of some diseases compared to the general population. A large amount of data is available on HIV/AIDS, but far less on other health problems. In this review we aimed to synthesize the knowledge on the burden of communicable and non-communicable diseases, mental health conditions and violence experienced by SGM, based on available systematic reviews. We conducted a global review of systematic reviews, including searching the Cochrane and the Campbell Collaboration libraries, as well as PubMed, using a range of search terms describing the populations of interest, without time or language restrictions. Google Scholar was also scanned for unpublished literature, and references of all selected reviews were checked to identify further relevant articles. We found 30 systematic reviews, all originally written in English. Nine reviews provided data on HIV, 12 on other sexually transmitted infections (STIs), 4 on cancer, 4 on violence and 3 on mental health and substance use. A quantitative meta-analysis was not possible. The findings are presented in a narrative format. Our review primarily showed that there is a high burden of disease for certain subpopulations of SGM in HIV, STIs, STI-related cancers and mental health conditions, and that they also face high rates of violence. Secondly, our review revealed many knowledge gaps. Those gaps partly stem from a lack of original research, but there is an equally urgent need to conduct systematic and literature reviews to assess what we already know on the disease burden in SGM. Additional reviews are needed on the non-biological factors that could contribute to the higher disease burden. In addition, to provide universal access to health-care for all, more information is needed on the barriers that SGM face in accessing health services, including the attitudes of health-care providers. Understanding these barriers and the additional health risks they impose is crucial to improving the health status of SGM. PMID- 26800683 TI - Whipworms in humans and pigs: origins and demography. AB - BACKGROUND: Trichuris suis and T. trichiura are two different whipworm species that infect pigs and humans, respectively. T. suis is found in pigs worldwide while T. trichiura is responsible for nearly 460 million infections in people, mainly in areas of poor sanitation in tropical and subtropical areas. The evolutionary relationship and the historical factors responsible for this worldwide distribution are poorly understood. In this study, we aimed to reconstruct the demographic history of Trichuris in humans and pigs, the evolutionary origin of Trichuris in these hosts and factors responsible for parasite dispersal globally. METHODS: Parts of the mitochondrial nad1 and rrnL genes were sequenced followed by population genetic and phylogenetic analyses. Populations of Trichuris examined were recovered from humans (n = 31), pigs (n = 58) and non-human primates (n = 49) in different countries on different continents, namely Denmark, USA, Uganda, Ecuador, China and St. Kitts (Caribbean). Additional sequences available from GenBank were incorporated into the analyses. RESULTS: We found no differentiation between human-derived Trichuris in Uganda and the majority of the Trichuris samples from non-human primates suggesting a common African origin of the parasite, which then was transmitted to Asia and further to South America. On the other hand, there was no differentiation between pig-derived Trichuris from Europe and the New World suggesting dispersal relates to human activities by transporting pigs and their parasites through colonisation and trade. Evidence for recent pig transport from China to Ecuador and from Europe to Uganda was also observed from their parasites. In contrast, there was high genetic differentiation between the pig Trichuris in Denmark and China in concordance with the host genetics. CONCLUSIONS: We found evidence for an African origin of T. trichiura which were then transmitted with human ancestors to Asia and further to South America. A host shift to pigs may have occurred in Asia from where T. suis seems to have been transmitted globally by a combination of natural host dispersal and anthropogenic factors. PMID- 26800684 TI - Health systems guidance appraisal--a critical interpretive synthesis. AB - BACKGROUND: Health systems guidance (HSG) are systematically developed statements that assist with decisions about options for addressing health systems challenges, including related changes in health systems arrangements. However, the development, appraisal, and reporting of HSG poses unique conceptual and methodological challenges related to the varied types of evidence that are relevant, the complexity of health systems, and the pre-eminence of contextual factors. To address this gap, we are conducting a program of research that aims to create a tool to support the appraisal of HSG and further enhance HSG development and reporting. The focus of this paper was to conduct a knowledge synthesis of the published and grey literatures to determine quality criteria (concepts) relevant for this process. METHODS: We applied a critical interpretive synthesis (CIS) approach to knowledge synthesis that enabled an iterative, flexible, and dynamic analysis of diverse bodies of literature in order to generate a candidate list of concepts that will constitute the foundational components of the HSG tool. Using our review questions as compasses, we were able to guide the search strategy to look for papers based on their potential relevance to HSG appraisal, development, and reporting. The search strategy included various electronic databases and sources, subject-specific journals, conference abstracts, research reports, book chapters, unpublished data, dissertations, and policy documents. Screening the papers and data extraction was completed independently and in duplicate, and a narrative approach to data synthesis was executed. RESULTS: We identified 43 papers that met eligibility criteria. No existing review was found on this topic, and no HSG appraisal tool was identified. Over one third of the authors implicitly or explicitly identified the need for a high-quality tool aimed to systematically evaluate HSG and contribute to its development/reporting. We identified 30 concepts that may be relevant to the appraisal of HSG and were able to cluster them into three meaningful domains: process principles, content, and context principles. CONCLUSIONS: Our study showed the role that the quality criteria play in the development, appraisal, and reporting of HSG and demonstrated the link and resonance within and between the various concepts in the three domains. PMID- 26800685 TI - Coexistence of congenital diaphragmatic hernia and abdominal wall closure defect with chromosomal abnormality: two case reports. AB - BACKGROUND: We reported two rare cases of congenital diaphragmatic hernia with abdominal wall closure defect, which were not associated with septum transversum diaphragmatic defects or Fryns syndrome. CASE PRESENTATION: Case 1: a Japanese baby boy was delivered at 37 weeks' gestation by urgent cesarean section because of the diagnosis of severe fetal distress. Congenital diaphragmatic hernia with omphalocele was prenatally diagnosed with fetal ultrasound. A ruptured omphalocele was confirmed at delivery. A silo was established on the day of his birth; direct closure of his diaphragmatic defect and abdominal wall closure was performed on the fifth day after his birth. Trisomy 13 was confirmed by genetic examination. His postoperative course was uneventful and he was discharged 5 months postnatally with home oxygen therapy. He was readmitted because of heart failure and died at 6 months. Case 2: a Japanese baby boy, who was prenatally diagnosed with gastroschisis, was delivered at 35 weeks' gestation by urgent cesarean section because of the diagnosis of fetal distress. Silo construction using a wound retractor was performed on the day of his birth and direct abdominal closure was performed on the tenth day after his birth. Trisomy 21 was confirmed by genetic examination. Treatment for his respiratory distress was continued after surgery. A retrosternal hernia was revealed at 6 months and direct closure of retrosternal diaphragm with the resection of hernia sac was performed. His postoperative course was uneventful and he was discharged with home oxygen therapy. CONCLUSIONS: Attention should be paid to chromosomal abnormality in cases in which the coexistence of congenital diaphragmatic hernia and abdominal wall closure defect are observed. PMID- 26800686 TI - Winged scapula incidence and upper limb morbidity after surgery for breast cancer with axillary dissection. AB - PURPOSE: The aim of this study was to determine the incidence of winged scapula after breast cancer surgery, its impact on shoulder morbidity and difference in incidence according to surgery type. METHODS: Patients with breast cancer and surgical indication for axillary dissection were included. A total of 112 patients were surveyed with one physical evaluation before the surgery and others 15, 30, 90, and 180 days after. Winged scapula was assessed with test proposed by Hoppenfeld. Shoulder range of motion (ROM) was assessed with goniometer for flexion, extension, adduction, abduction, internal rotation, and external rotation. A verbal scale from 0 to 10 was used to assess pain. RESULTS: Winged scapula incidence was 8.0 % 15 days after surgery. Two patients recovered from winged scapula 90 days after surgery and four more 180 days after surgery, while three patients still had winged scapula at this time. The incidence after 15 days from surgery was 20.9 and 22.6 % among patients submitted to sentinel node biopsy or axillary lymphadenectomy (AL), respectively (p < 0.01). There was no statistical difference of incidence according to breast surgery type. Operated side shoulder flexion, adduction, and abduction ROM changes were statistically different in patients with or without winged scapula. The mean reduction was higher in patients with winged scapula. Both groups showed the same pattern over time in pain. CONCLUSION: Winged scapula incidence was 8.0 % and was higher in AL, and prevalence decreased during 6 months after surgery. Patients who developed winged scapula had more shoulder flexion, adduction, and abduction limitation. PMID- 26800687 TI - A 5-year exercise program in children improves muscle strength without affecting fracture risk. AB - PURPOSE: High level of physical activity (PA) is associated with great muscle strength and high fracture risk. This prospective controlled population-based study evaluated how a pediatric PA intervention program influenced muscle strength and fracture risk. METHODS: We carried out a school-based exercise intervention program with 200 min of PA per week for 5 years in 335 girls and 408 boys aged 6-9 years at study start. An age-matched control cohort including 756 girls and 782 boys continued with 60 min of PA per week. We registered fractures during the study period and calculated rate ratio. In a sub-sample, including 74 girls and 107 boys in the intervention and 51 girls and 54 boys in the control group, we measured knee flexion and extension strength by a computerized dynamometer and leg composition by dual energy X-ray absorptiometry. Group comparisons were adjusted for differences in age, baseline value for the measured parameter and changes in height. RESULTS: Children in the intervention group had a rate ratio to sustain a fracture of 1.03 (0.78, 1.36) (mean and 95 % confidence interval) (p = 0.79). The annual gain in flexion peak torque muscle strength was greater in both girls (at 60 degrees /s) [1.1 Nm (0.5, 1.8), p < 0.01] and boys (at 180 degrees /s) [0.7 Nm (0.1, 1.2), p < 0.05] in the intervention than in the control group, while leg composition was similar. CONCLUSION: Increased PA during a 5-year period, starting in the pre-pubertal period, improves the gain in muscle strength without affecting the fracture risk. PMID- 26800688 TI - Conditioned stimuli's role in relapse: preclinical research on Pavlovian Instrumental-Transfer. AB - RATIONALE AND OBJECTIVE: Pavlovian learning is central to many theories of addiction. In these theories, stimuli paired with drug ingestion become conditioned stimuli (CS) and subsequently elicit drug-seeking and drug-taking. However, in most relevant studies, Pavlovian and instrumental learning are confounded. This confound may be avoided in Pavlovian-Instrumental-Transfer (PIT) procedures. In PIT, Pavlovian and instrumental learning are established separately and then combined. In order to better understand the role of CSs in addiction, we review the relevant studies using PIT. FINDINGS: We identified seven articles examining PIT effects of ethanol- or cocaine-paired CSs. Under at least one condition, six of these articles reported CS-elicited increases in responding previously maintained by drug. However, the only study using the optimal control condition failed to find a CS-elicited increase. Two studies examining CS specificity found the CS also increased responding maintained by a different reinforcer. Two studies examined if CSs elicit increases in actual drug taking. Both failed to find CS-elicited increases, i.e., no study shows CS elicited increases in actual drug-taking. Further, CS-elicited increases in extinguished responding are short-lived. CONCLUSIONS: These findings are not entirely consistent with Pavlovian learning playing a central role in addiction. However, design issues can explain most of these inconsistencies. Studies without these design issues are needed. Additionally, existing theories hypothesize drug paired CSs increase drug-taking by increasing motivation, by eliciting conditioned responses that make drug-seeking more probable, or by a combination of these. Work distinguishing between these mechanisms would also be useful. PMID- 26800689 TI - c.3623G > A mutation encodes a CFTR protein with impaired channel function. AB - BACKGROUND: The aims of this study were to characterize clinical features of a pediatric African-American cystic fibrosis (CF) patient heterozygous for F508del and a novel c.3623G > A mutation, and to identify the molecular defect(s) associated with c.3623G > A mutation. METHODS: The medical record of this patient was analyzed retrospectively. Western blotting and iodide efflux assay were used to study mutant CFTR protein expression level, maturation status, channel function, and the effects of CFTR modulation on these characteristics. RESULTS: The encoding protein of c.3623G > A mutation, G1208D-CFTR, has a moderate processing defect and exhibits impaired channel function, which were partially rescued by using VX-809 or exposed to low temperature (28 degrees C). The patient has mild CF disease manifestations. CONCLUSIONS: Our biochemical findings correlate with the clinical phenotype and suggest that c.3623G > A is a CF causing mutation. The study helps expand our knowledge of rare CFTR mutations in a minority population and may have important clinical implications for personalized therapeutic intervention. PMID- 26800690 TI - Exposure of the murine RAW 264.7 macrophage cell line to dicalcium silicate coating: assessment of cytotoxicity and pro-inflammatory effects. AB - Inflammatory effects are significant elements of the immune response to biomaterials. Previously, we reported inflammatory effects in response to dicalcium silicate (Ca2SiO4, C2S) particles. However, the immunological effects of C2S coatings have not been studied. C2S often used as coatings materials in orthopedic and dentistry applications. It may have different effect from C2S particles. Further, it remains unclear whether C2S coating is equally biocompatible as 45S5 coating. The aim of this study was to test the cytotoxicity and pro-inflammatory effects of C2S coating on RAW 264.7 macrophages. C2S and 45S5 coatings were characterized using scanning electron microscopy (SEM), atomic force microscopy (AFM), energy dispersive analysis (EDS) and X-ray diffraction (XRD). inductively coupled plasma optical emission spectroscopy (ICP-OES) was used to detect ionic concentrations after soaking coated discs in medium. The cytotoxicity of C2S and 45S5 coatings against RAW 264.7 macrophages was measured using the LDH Cytotoxicity Assay Kit, Cell Counting Kit-8 (CCK-8) assays and flow cytometry for apoptosis assays. The gene and protein expression of TNF-alpha, IL 6 and IL-1beta were detected using RT-q PCR and ELISA, respectively. The tested coating materials are not cytotoxic to macrophages. The C2S-coated surface stimulated macrophages to express pro-inflammatory mediators, such as TNF-alpha, IL-6 and IL-1beta, and C2S coating caused less IL-6 but greater IL-1beta production than the 45S5 coating. C2S coating have no cytotoxicity when directly cultured with macrophages. C2S and 45S5 coatings both have the potential to induce pro-inflammatory effects, and the biocompatibility of C2S is similar to that of 45S5. PMID- 26800691 TI - Shear stress and circumferential stretch by pulsatile flow direct vascular endothelial lineage commitment of mesenchymal stem cells in engineered blood vessels. AB - Understanding the response of mesenchymal stem cells (MSCs) in the dynamic biomechanical vascular environment is important for vascular regeneration. Native vessel biomechanical stimulation in vitro is thought to be the most important contributor to successful endothelial differentiation of MSCs. However, the appropriate biomechanical stimulation conditions for differentiating MSCs into ECs have not been fully investigated. To accomplish an in vivo-like loading environment, a loading system was designed to apply flow induced stress and induce hMSC differentiation in vascular cells. Culturing MSCs on tubular scaffolds under flow-induced shear stress (2.5 dyne/cm(2)) for 4 days results in increased mRNA levels of EC markers (vWF, CD31, VE-cadherin and E-selectin) after one day. Furthermore, we investigated the effects of 2.5 dyne/cm(2) shear stress followed by 3% circumferential stretch for 3 days, and an additional 5% circumferential stretch for 4 days on hMSC differentiation into ECs. EC marker protein levels showed a significant increase after applying 5% stretch, while SMC markers were not present at levels sufficient for detection. Our results demonstrate that the expression of several hMSC EC markers cultured on double layered tubular scaffolds were upregulated at the mRNA and protein levels with the application of fluid shear stress and cyclic circumferential stretch. PMID- 26800692 TI - Elastomeric enriched biodegradable polyurethane sponges for critical bone defects: a successful case study reducing donor site morbidity. AB - Bone substitutes have been a critical issue as the natural source can seldom provide enough bone to support full healing. No bone substitute complies with all necessary functions and characteristics that an autograft does. Polyurethane sponges have been used as a surgical alternative to cancellous bone grafts for critical bone defect donor sites. Critical bone defects were created on the tibial tuberosity and iliac crest using an ovine model. In group I (control untreated), no bone regeneration was observed in any animal. In group II (defects left empty but covered with a microporous polymeric membrane), the new bone bridged the top ends in all animals. In groups III and IV, bone defects were implanted with polyurethane scaffolds modified with biologically active compounds, and bone regeneration was more efficient than in group II. In groups III and IV there were higher values of bone regeneration specific parameters used for evaluation (P < 0.05) although the comparison between these groups was not possible. The results obtained in this study suggest that biodegradable polyurethane substitutes modified with biologically active substances may offer an alternative to bone graft, reducing donor site morbidity associated with autogenous cancellous bone harvesting. PMID- 26800693 TI - Multi and single walled carbon nanotubes: effects on cell responses and biomineralization of osteoblasts cultures. AB - The use of carbon nanotubes (CNTs) on the development of biomaterials has been motivated by their excellent mechanical properties that could improve synthetic bone materials. However, the toxicity of CNTs on the tissue/implant interface and their influence on the biomineralization process have some contradictions. We investigated the influence of CNTs on osteoblasts plated on titanium (Ti) discs or plastic surfaces. We evaluated osteoblasts viability, alkaline phosphatase (ALP) activity, and mineralized matrix formation in the different phases of osteoblasts growth in the presence of single-walled CNTs (SWCNTs) and multi walled CNTs (MWCNTs). An increase in osteoblasts viability was observed at the 21st day for both CNTs on plastic surface, while viability increased for MWCNTs at the 7th and 14th days and at the 7th day for SWCNTs on Ti discs compared to control. ALP activity increased at the 14th and 21st days for MWCNTs on plastic surfaces. For cells incubated with SWCNTs, an increase in ALP activity at the 7th day for plastic surface and at the 14th day for both materials (plastic and Ti) was observed. The mineralized matrix formation increased at the 21st day on plastic surface with SWCNTs, and at the 14th and 21st days for both CNTs on Ti discs. In conclusion, both SWCNTs and MWCNTs are not toxic to osteoblasts at concentrations up to 5 * 10(-5) and 1.3 * 10(-2) mg/mL, respectively, either in Ti discs or plastic surfaces. In the long term, the cells grown in contact with both CNTs and Ti presented better results regarding bone-like nodules formation. PMID- 26800695 TI - In silico screening of the chicken genome for overlaps between genomic regions: microRNA genes, coding and non-coding transcriptional units, QTL, and genetic variations. AB - MicroRNAs (miRNAs) are a class of non-coding RNAs involved in posttranscriptional regulation of target genes. Regulation requires complementarity between target mRNA and the mature miRNA seed region, responsible for their recognition and binding. It has been estimated that each miRNA targets approximately 200 genes, and genetic variability of miRNA genes has been reported to affect phenotypic variability and disease susceptibility in humans, livestock species, and model organisms. Polymorphisms in miRNA genes could therefore represent biomarkers for phenotypic traits in livestock animals. In our previous study, we collected polymorphisms within miRNA genes in chicken. In the present study, we identified miRNA-related genomic overlaps to prioritize genomic regions of interest for further functional studies and biomarker discovery. Overlapping genomic regions in chicken were analyzed using the following bioinformatics tools and databases: miRNA SNiPer, Ensembl, miRBase, NCBI Blast, and QTLdb. Out of 740 known pre-miRNA genes, 263 (35.5 %) contain polymorphisms; among them, 35 contain more than three polymorphisms The most polymorphic miRNA genes in chicken are gga-miR-6662, containing 23 single nucleotide polymorphisms (SNPs) within the pre-miRNA region, including five consecutive SNPs, and gga-miR-6688, containing ten polymorphisms including three consecutive polymorphisms. Several miRNA-related genomic hotspots have been revealed in chicken genome; polymorphic miRNA genes are located within protein-coding and/or non-coding transcription units and quantitative trait loci (QTL) associated with production traits. The present study includes the first description of an exonic miRNA in a chicken genome, an overlap between the miRNA gene and the exon of the protein-coding gene (gga-miR-6578/HADHB), and the first report of a missense polymorphism located within a mature miRNA seed region. Identified miRNA-related genomic hotspots in chicken can serve researchers as a starting point for further functional studies and association studies with poultry production and health traits and the basis for systematic screening of exonic miRNAs and missense/miRNA seed polymorphisms in other genomes. PMID- 26800696 TI - Levetiracetam Pharmacokinetics During Continuous Venovenous Hemofiltration and Acute Liver Dysfunction. AB - BACKGROUND: Levetiracetam clearance is dependent on renal (major) and hepatic (minor) elimination pathways. In the setting of organ dysfunction, dose reductions are recommended to prevent accumulation. Continuous venovenous hemofiltration (CVVH) has been shown to eliminate levetiracetam, but the preferred dosing regimen when a patient is on CVVH and has concomitant acute liver dysfunction is unknown. The objective of this case is to describe levetiracetam dosing and pharmacokinetics in the setting of CVVH and acute liver dysfunction. METHODS: This is a case report of a single patient. RESULTS: A 59 year-old male was admitted to the intensive care unit for acute onset multiorgan dysfunction associated with a hematologic disorder. His hospital course was complicated by persistent liver dysfunction with a model for end-stage liver disease score of 47 and renal failure which necessitated initiation of CVVH. On hospital day two, the patient developed new-onset focal seizures secondary to metabolic abnormalities that resulted in the initiation of levetiracetam 1000 mg intravenously twice daily. The peak concentration at steady state was 32.2 mcg/mL, and the trough concentration was 16.1 mcg/mL (goal 12-46 mcg/mL). The volume of distribution was 0.65 L/kg, and the elimination half-life was 11.4 h. CONCLUSION: Levetiracetam pharmacokinetics observed in this case approximated those seen in a normal healthy patient and a regimen of 1000 mg twice daily achieved serum trough concentrations at the lower limit of the target range. This case indicates that in a patient with acute liver dysfunction on CVVH, 1000 mg twice daily may be considered as an empiric levetiracetam regimen. PMID- 26800694 TI - Textile cell-free scaffolds for in situ tissue engineering applications. AB - In this article, the benefits offered by micro-fibrous scaffold architectures fabricated by textile manufacturing techniques are discussed: How can established and novel fiber-processing techniques be exploited in order to generate templates matching the demands of the target cell niche? The problems related to the development of biomaterial fibers (especially from nature-derived materials) ready for textile manufacturing are addressed. Attention is also paid on how biological cues may be incorporated into micro-fibrous scaffold architectures by hybrid manufacturing approaches (e.g. nanofiber or hydrogel functionalization). After a critical review of exemplary recent research works on cell-free fiber based scaffolds for in situ TE, including clinical studies, we conclude that in order to make use of the whole range of favors which may be provided by engineered fibrous scaffold systems, there are four main issues which need to be addressed: (1) Logical combination of manufacturing techniques and materials. (2) Biomaterial fiber development. (3) Adaption of textile manufacturing techniques to the demands of scaffolds for regenerative medicine. (4) Incorporation of biological cues (e.g. stem cell homing factors). PMID- 26800697 TI - Default Mode Network Perfusion in Aneurysmal Subarachnoid Hemorrhage. AB - BACKGROUND: The etiology of altered consciousness in patients with high-grade aneurysmal subarachnoid hemorrhage (SAH) is not thoroughly understood. We hypothesized that decreased cerebral blood flow (CBF) in brain regions critical to consciousness may contribute. METHODS: We retrospectively evaluated arterial spin labeled (ASL) perfusion magnetic resonance imaging (MRI) measurements of CBF in 12 patients with aneurysmal SAH admitted to our neurocritical care unit. CBF values were analyzed within gray matter nodes of the default mode network (DMN), whose functional integrity has been shown to be necessary for consciousness. DMN nodes studied were the bilateral medial prefrontal cortices, thalami, and posterior cingulate cortices. Correlations between nodal CBF and admission Glasgow Coma Scale (GCS) score, admission Hunt and Hess (HH) class, and GCS score at the time of MRI (MRI GCS) were tested. RESULTS: Spearman's correlation coefficients were not significant when comparing admission GCS, admission HH, and MRI GCS versus nodal CBF (p > 0.05). However, inter-rater reliability for nodal CBF was high (r = 0.71, p = 0.01). CONCLUSIONS: In this retrospective pilot study, we did not identify significant correlations between CBF and admission GCS, admission HH class, or MRI GCS for any DMN node. Potential explanations for these findings include small sample size, ASL data acquisition at variable times after SAH onset, and CBF analysis in DMN nodes that may not reflect the functional integrity of the entire network. High inter-rater reliability suggests ASL measurements of CBF within DMN nodes are reproducible. Larger prospective studies are needed to elucidate whether decreased cerebral perfusion contributes to altered consciousness in SAH. PMID- 26800698 TI - Case-control study of GRIA1 and GRIA3 gene variants in migraine. AB - BACKGROUND: As the most abundant excitatory neurotransmitter in the central nervous system, glutamate has been accepted to play a major role in the pathophysiology of migraine. The previous studies have reported the glutamate receptor ionotropic GRIA1 and GRIA3 genes variants associated with migraine. The project aims to investigate the polymorphisms in both genes for their association with migraine in the Chinese Han population. METHODS: A Han-Chinese case-control population, including 331 unrelated female migraine patients and 330 matched controls, was studied. Variants in genes (GRIA1 and GRIA3) were genotyped by Multiplex SNaPshot assay. RESULTS: In the group of patients, the frequency of allele C was 84.1 % (557 C alleles) and allele T was 15.9 % (105 T alleles) for the GRIA1 (rs2195450) in migraineurs, this was significantly as compared with the controls (P = .001, OR = 1.786, 95 % CI: 1.28-2.49). And an association was also seen in the migraine with aura (MA) subtype (P = .012, OR = 2.092, 95 % CI: 1.17 3.76) and migraine without aura (MO) subtype (P = .002, OR = 1.737, 95 % CI: 1.23 2.45). However, no evidence was found that GRIA1 (rs548294) or GRIA3 (rs3761555) is associated with migraine. CONCLUSION: Our data of this study confirmed the association of GRIA1 (rs2195450) to female migraine (MA, MO) susceptibility in the Chinese Han population. The result provides evidence that the glutamatergic system is implicated in the pathophysiology of migraine. PMID- 26800699 TI - Bioactive cyclolanstane-type saponins from the stems of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao. AB - Twelve cyclolanstane-type saponins including six new ones, astrolanosaponins A1 (1), A2 (2), B (3), C (4), D (5), and E (6) were obtained from the stem of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, and their structures were elucidated by chemical and spectroscopic methods. Of the known ones, cycloastragenol-3-O-beta-D-glucopyranoside (7), astraverrucin II (8), cycloaraloside E (9), huangqiyenin A (10), and huangqiyenin B (11) were isolated from the species first. Meanwhile, compounds 1-3, 5-9, and aleksandroside I (12) showed inhibitory effects on triglyceride accumulation in HepG2 cells. PMID- 26800700 TI - Working with Persistent Pain: An Exploration of Strategies Utilised to Stay Productive at Work. AB - Purpose Maintaining productive employment for people with persistent pain conditions is challenging. This study aims to explore supports-work and non-work- used by employees to assist them in maintaining productive employment. Methods An exploratory, mixed-methods study comprising a questionnaire battery followed by semi-structured interviews to collect in-depth qualitative data was undertaken. The questionnaires measured descriptive variables used to select participants for interviews based on maximum heterogeneity sampling. Thirty-five semi-structured interviews were undertaken (14 males; 21 females). The interview schedule covered: employment situation, workplace challenges, workplace supports, coping strategies, motivations, future employment options and any other resources utilised. Inductive content analysis was undertaken using a grounded theory approach to systematically explore the data. Results Three key themes were identified: barriers to working productively, enablers to working productively, disclosing my condition at work. A key determinant of maintaining productive employment was a supportive employer. In addition, flexibility in the work organisation was also pivotal in maintaining sustainable, productive employment. An important issue emerged with regard to disclosure of one's condition to an employer. For some, this was a significant barrier to employment. Conclusions To ensure sustainable employment is attainable for those with persistent pain conditions, a good match is required between an employee and their work. Workplace accommodations may assist with improving job fit but this requires disclosure of a condition to an employer. Weighing up the risks and benefits of disclosure is difficult, and may be assisted by knowledge of available supports to assist with maintaining ongoing employment. PMID- 26800701 TI - Is there an added value of a hepatobiliary phase with gadoxetate disodium following conventional MRI with an extracellular gadolinium agent in a single imaging session for detection of primary hepatic malignancies? AB - PURPOSE: To determine added value of hepatobiliary phase (HBP) using gadoxetate disodium compared to MRI with extracellular gadolinium-based contrast agent (GBCA) for detection of primary hepatic malignancies in a single imaging session. MATERIALS AND METHODS: IRB approved this HIPAA compliant retrospective study. Within 90 days of resection or liver transplant, thirty patients underwent MRI with extracellular GBCA followed by separate injection of gadoxetate for HBP. Two sets of images were reviewed: Set #1-unenhanced and enhanced images with an extracellular GBCA and set #2-with addition of HBP. Data were analyzed in two groups, cases with hepatocellular carcinoma (HCC) only and cases with either HCC and/or cholangiocarcinoma. Observer diagnostic accuracy (Az), sensitivity, and specificity were calculated. RESULTS: 14/30 subjects had HCC (46%, CI 28-66%), 2/30 (2%, CI 1-22%) cholangiocarcinoma, and 14/30 (46%, CI 28-66%) no malignancy. There was no significant change in A z value with addition of gadoxetate in the detection of HCC (range 0.84-0.97 set #1 and 0.85-0.97 set #2, p > 0.05). Sensitivity and specificity showed no significant differences (p > 0.05) between the image sets for all readers. When stratified by lesion size, there was no significant difference in accuracy, sensitivity, or specificity for any reader (p > 0.05). CONCLUSION: When compared to extracellular GBCA, gadoxetate HBP imaging does not result in a significant difference in accuracy or sensitivity in diagnosis of HCC or cholangiocarcinoma and may result in a decrease in specificity. PMID- 26800702 TI - Identification, cloning and characterization of R2R3-MYB gene family in canola (Brassica napus L.) identify a novel member modulating ROS accumulation and hypersensitive-like cell death. AB - The R2R3-MYB proteins comprise one of the largest families of transcription factors in plants. Although genome-wide analysis of this family has been carried out in some plant species, little is known about R2R3-MYB genes in canola (Brassica napus L.). In this study, we have identified 76 R2R3-MYB genes in the canola genome through mining of expressed sequence tags (ESTs). The cDNA sequences of 44 MYB genes were successfully cloned. The transcriptional activities of BnaMYB proteins encoded by these genes were assayed in yeast. The subcellular localizations of representative R2R3-MYB proteins were investigated through GFP fusion. Besides, the transcript abundance level analysis during abiotic conditions and ABA treatment identified a group of R2R3-MYB genes that responded to one or more treatments. Furthermore, we identified a previously functionally unknown MYB gene-BnaMYB78, which modulates reactive oxygen species (ROS)-dependent cell death in Nicotiana benthamiana, through regulating the transcription of a few ROS- and defence-related genes. Taken together, this study has provided a solid foundation for understanding the roles and regulatory mechanism of canola R2R3-MYB genes. PMID- 26800704 TI - Use texts, apps, and Skype to keep young people with diabetes engaged with services, says guidance. PMID- 26800703 TI - Sudden Cardiac Arrest and Rare Genetic Variants in the Community. AB - BACKGROUND: Sudden cardiac arrest (SCA) ranks among the most common causes of death worldwide. Because SCA is most often lethal, yet mostly occurs in individuals without previously known cardiac disease, the identification of patients at risk for SCA could save many lives. In unselected SCA victims from the community, common genetic variants (which are not disease-causing per se, but may increase susceptibility to ventricular fibrillation) are found to be associated with increased SCA risk. However, whether rare genetic variants contribute to SCA risk in the community is largely unexplored. METHODS AND RESULTS: We here investigated the involvement of rare genetic variants in SCA risk at the population level by studying the prevalence of 6 founder genetic variants present in the Dutch population (PLN-p.Arg14del, MYBPC3-p.Trp792fsX17, MYBPC3-p.Arg943X, MYBPC3-p.Pro955fsX95, PKP2-p.Arg79X, and the Chr7q36 idiopathic ventricular fibrillation risk haplotype) in a cohort of 1440 unselected Dutch SCA victims included in the Amsterdam Resuscitation Study (ARREST). The six studied founder mutations were found to be more prevalent (1.1%) in the ARREST SCA cohort compared with an ethnically and geographically matched set of controls (0.4%, n=1379; P<0.05) or a set of Dutch individuals drawn from the Genome of the Netherlands (GoNL) study (0%, n=500; P<0.02). CONCLUSIONS: This finding provides proof-of-concept for the notion that rare genetic variants contribute to some extent to SCA risk in the community. PMID- 26800705 TI - Low C4, C4A and C4B gene copy numbers are stronger risk factors for juvenile onset than for adult-onset systemic lupus erythematosus. AB - OBJECTIVE: Complete deficiency of Complement C4 component is a strong genetic risk factor for SLE. C4 is encoded by two different genes, C4A and C4B, which show considerable gene copy number (GCN) variation. This study investigates the association of total C4, C4A and C4B GCN with JSLE. METHODS: Ninety JSLE patients, 170 adult-onset SLE (aSLE) patients and 200 healthy individuals were evaluated for C4A and C4B GCN by quantitative real-time PCR. RESULTS: JSLE patients had lower GCN for C4A (mean = 1.7; 95% CI: 1.5, 1.9) and C4B (mean = 1.5; 95% CI: 1.3, 1.6) compared with healthy individuals (mean C4A = 2.3; 95% CI: 2.2, 2.5, P < 0.001; C4B = 2.0; 95% CI: 1.8, 2.1; P < 0.001) or with aSLE patients (mean C4A = 1.9; 95% CI: 1.8, 2.1, P = 0.006; mean C4B = 1.8; 95% CI: 1.7, 1.9, P < 0.001). Low total C4 GCN (<4 copies) was more frequent in JSLE than in healthy individuals (59% vs 28%; P < 0.001). The same was observed for low C4A (?1 copy) (52% vs 18%; P < 0.001) and for low C4B (60% vs 31%; P < 0.001). JSLE had a stronger association with low total C4 (OR = 3.68, 95% CI: 2.19, 6.20), C4A (OR = 4.98, 95% CI: 2.88, 8.62) and C4B (OR = 3.26; 95% CI: 1.95, 5.47) than aSLE (C4 OR = 2.03; 95% CI: 1.32, 3.13; C4A OR = 2.36; 95% CI: 1.46, 3.81; C4B OR = 1.13; 95% CI: 0.73, 1.74). In addition, pericarditis in JSLE patients was associated with low C4 (OR = 4.13; 95% CI: 1.02, 16.68; P = 0.047) and low C4A (OR = 5.54; 95% CI: 1.37, 22.32; P = 0.016). CONCLUSION: Low total C4, C4A and C4B GCN were associated with a stronger risk for developing JSLE than aSLE. Additionally, low total C4 and C4A GCN are risk factors for pericarditis in JSLE. PMID- 26800707 TI - Government made concessions on weekend working for junior doctors, leaked letter shows. PMID- 26800706 TI - Aggravation of Helicobacter pylori stomach infections in stressed military recruits. AB - OBJECTIVE: To investigate the effect of military stress on immune response and Helicobacter pylori stomach infections. METHODS: In this prospective, observational study, the Symptom Checklist-90 questionnaire was completed by military recruits before and following a 3-month basic training programme. H. pylori immunoglobulin (Ig)G levels, C(14)-urea breath-test values and levels of cortisol, catecholamine, and certain humoral and cellular immune responses were measured before and after the basic training. RESULTS: For 60 military recruits, somatization, depression and paranoid ideation scores were significantly increased after, compared with before, basic training. Post-training H. pylori IgG detection revealed three additional cases of H. pylori infection. Post training C(14)-urea breath-test values were significantly higher compared with before training - thus suggesting higher levels of H. pylori colonization in the stomach. Post-training cortisol and catecholamine levels were increased, while serum IgG levels were decreased; complement component (C)3 and C4 levels remained unchanged. Post-training CD4(+) and CD8(+) T-cell percentages and the CD4(+)/CD8(+) ratio were significantly reduced compared with before training. Serum interleukin (IL)-2 levels were lower and IL-10 levels were higher following training and there was a significant decrease in the IL-2/IL-10 ratio. CONCLUSION: Military stress may reduce humoral and cellular immune responses and may aggravate the severity of H. pylori infection. PMID- 26800708 TI - A critical comparison of welfare states and their relevance to people with an intellectual disability. AB - This article compares the welfare services for adults with an intellectual disability in three European countries: England, Norway and Sweden. The purpose of the comparison is to develop an understanding of the welfare state and institutional contexts of the country-specific policies and to develop a critical analysis through a comparative method based on selected secondary literature. Typological frameworks of European welfare states are applied as analytic frameworks to enable comparison between the countries. It is argued that there are international policy developments but these are shaped at a national level by different types of welfare states and histories. Through a comparison of similarities and differences, the article suggests that international policy ideas that impact on the lives of people with intellectual disabilities are mediated by different types of welfare states and institutions. PMID- 26800709 TI - Incidence and survival trends for malignant pleural and peritoneal mesothelioma, Australia, 1982-2009. AB - BACKGROUND: Australia is known to have had one of the highest per-capita asbestos consumption rates, yet there are few contemporary reports on malignant mesothelioma trends. METHODS: Data on 10 930 people with malignant pleural mesothelioma (MPM) and 640 people with malignant peritoneal mesothelioma diagnosed in Australia during 1982-2009 were analysed. Observed incidence rate trends were quantified. Incidence rates were projected up to 2030 using observed incident cases during 1982-2012. The relative per-decade change in excess mortality during 1999-2009 was estimated. RESULTS: During 1982-2009, acceleration in MPM age-standardised incidence rates were highest for women and those aged 75 years and above, with average annual percentage changes of +4.9 (95% CI 3.6 to 6.2) and +7.2 (95% CI 5.4 to 9.0), respectively. Age-standardised incidence rates for men with MPM aged 0-64 years decelerated rapidly during 2003-2009, an average annual percentage change of -5.1% (95% CI -7.6% to -2.5%). Overall, male age specific MPM incidence rates in the age group of 65-74 year during 2010-2030 are projected to decline with rates projected to increase for older men and women with MPM. There was a statistically significant 16% relative reduction in the excess mortality rate (EMR) up to 5 years postdiagnosis for people diagnosed with malignant pleural and peritoneal mesothelioma combined in 2009 compared with those diagnosed in 1999, an EMR ratio of 0.84 (95% CI 0.77 to 0.92). CONCLUSIONS: Australia's malignant mesothelioma incidence rates appear to have reached maximum levels but with differences over time by age, gender and tumour location. Improvements over time in survival provide a glimpse of hope for this almost invariably fatal disease. PMID- 26800710 TI - Comparative epidemiology of incident Parkinson's disease in Cambridgeshire, UK. PMID- 26800711 TI - Myelin injury without astrocytopathy in neuroinflammatory disorders with MOG antibodies. PMID- 26800712 TI - Unpacking the Black Box: A Formative Research Approach to the Development of Theory-Driven, Evidence-Based, and Culturally Safe Text Messages in Mobile Health Interventions. AB - BACKGROUND: Mobile-cellular subscriptions have increased steadily over the past decade. The accessibility of SMS messages over existing mobile networks is high and has almost universal availability even on older and unsophisticated mobile phones and in geographic settings where wireless coverage is weak. There is intensive exploration of this inexpensive mobile telecommunication technology to improve health services and promote behavior change among vulnerable populations. However, a neglected area of research is the documentation and critical analysis of the formative research process required in the development and refinement of effective SMS messages. OBJECTIVE: The objective of this qualitative research study was to identify major factors that may impact on the effectiveness of evidence-based SMS messages designed to reduce health inequities in hypertension management in low resource settings, including Aboriginal populations in high income countries and rural populations in low-income countries. Specifically, we were interested in uncovering the range of mediators that impact on appropriate message content transmission and, ultimately, on health behavior improvements in a range of these sociocultural settings. METHODS: Collaborative qualitative research with Canadian Aboriginal and Tanzanian participants was conducted to deconstruct the content and transmission of evidence-based health information contained in SMS messages in the context of an international research project designed to address health inequalities in hypertension, and to develop a grounded theory of the major factors that mediate the effectiveness of this communication. We also examined the interrelationship of these mediators with the three essential conditions of the behavior system of the Behavioral Change Wheel model (capability, opportunity, and motivation) and cultural safety. RESULTS: Four focus groups with a total of 45 participants were conducted. Our grounded theory research revealed how discrepancies develop between the evidence-based text message created by researchers and the message received by the recipient in mobile health interventions. These discrepancies were primarily generated by six mediators of meaning in SMS messages: (1) negative or non-affirming framing of advocacies, (2) fear- or stress-inducing content, (3) oppressive or authoritarian content, (4) incongruity with cultural and traditional practices, (5) disconnect with the reality of the social determinants of health and the diversity of cultures within a population, and (6) lack of clarity and/or practicality of content. These 6 mediators of meaning provide the basis for sound strategies for message development because they impact directly on the target populations' capability, opportunity, and motivation for behavior change. CONCLUSIONS: The quality of text messages impacts significantly on the effectiveness of a mobile health intervention. Our research underscores the urgent need for interventions to incorporate and evaluate the quality of SMS messages and to examine the mediators of meaning within each targeted cultural and demographic group. Reporting on this aspect of mobile health intervention research will allow researchers to move away from the current black box of SMS text message development, thus improving the transparency of the process as well as the quality of the outcomes. PMID- 26800713 TI - Improvement in Sperm Parameters With Traditional Iranian Remedy: A Case Report. AB - INTRODUCTION: Idiopathic male infertility is a global problem with almost no definite medicinal treatment. Most patients have to go through intrauterine insemination or assisted reproductive technology for achieving fertility. Unfortunately, success rates are low in cases with very low sperm count. Therefore it seems that improvement in sperm quality can have beneficial effects on assisted reproductive technology outcome. CASE REPORT: A 39-year-old man with history of infertility for 6 years was referred to the traditional medicine clinic with a recurrent unsuccessful intracytoplasmic sperm injection trial. His sperm analysis showed severe oligoasthenoteratozoospermia. After taking a traditional remedy he had a remarkable improvement in his sperm parameters, which led to the formation of 8 embryos in the following intracytoplasmic sperm injection cycle. CONCLUSION: Traditional medicine presents various food and remedy options for treating male infertility. It seems that combination therapy can be beneficial in obtaining better results in treatment of male idiopathic infertility. PMID- 26800714 TI - Antihyperlipidemic Effect of Syrian Mesquite (Prosopis farcta) Root in High Cholesterol Diet-Fed Rabbits. AB - Prosopis farcta root has been proposed as an efficacious natural drug for cardiovascular disorders in traditional medicine. The present study evaluates the efficacy of aqueous extract of Prosopis farcta root on experimental atherosclerosis development in rabbits with high cholesterol diet-induced hypercholesterolemia. Serum lipid parameters were significantly increased in the high cholesterol diet groups in comparison with the normal control group (P < .050). Histopathological findings revealed that atheromatous plaques were formed in both thoracic and abdominal aorta of hypercholestrolemic rabbits. Treatment with Prosopis farcta root significantly reduced total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, and very low density lipoprotein levels compared to high cholesterol diet rabbits (P < .050). This finding may reflect a reduction of chest pain or the beneficial effects of this plant root extract on cardiovascular health. The present study can serve as a basis for future investigations on the other effects of this plant on cardiovascular health. PMID- 26800715 TI - Are web-based questionnaires accepted in patients attending rehabilitation? AB - PURPOSE: The aim of the present paper was to study preferences for web based self administered questionnaires (web SAQs) vs. paper-based self-administered questionnaires (paper SAQs) and to evaluate the feasibility of using web SAQs in patients referred to cardiac, lung, occupational and cancer rehabilitation programs. METHODS: The patients were approached by mail and given the choice to answer the compulsory SAQs either on paper or on a web-based platform. RESULTS: Hundred and twenty seven out of 183 eligible patients (69.3%) were willing to participate and 126 completed the study. Web SAQs were preferred by 77.7%, and these patients were significantly younger, more often cohabiting and tended to have higher level of education than paper SAQ users. Mean number of data missing per patient was less among the web SAQ users than the paper SAQ users (0.55 vs. 2.15, p < 0.001). Costs related to human resources were estimated to be 60% lower with web SAQs compared to paper SAQs. CONCLUSIONS: Web SAQs were well accepted among the patients scheduled for rehabilitation, led to less missing data and considerable cost savings related to human resources. Patients referred to rehabilitation should be offered the choice to complete self-administered questionnaires on internet platforms when internet access is common and available. Implications for Rehabilitation The high acceptability of web-based self-administered questionnaires among rehabilitation patients suggests that internet platforms are suitable tools to collect patient information for rehabilitation units. Web-based modes of patient data collection demonstrate low number of missing data and can therefore improve the quality of data collection from rehabilitation patients. Use of web-based questionnaires considerably reduces administrative costs of data collection in rehabilitation settings compared to traditional pen and paper methods. PMID- 26800750 TI - Data Resource Profile: The Aberdeen Maternity and Neonatal Databank (AMND). PMID- 26800751 TI - Causality and causal inference in epidemiology: the need for a pluralistic approach. AB - Causal inference based on a restricted version of the potential outcomes approach reasoning is assuming an increasingly prominent place in the teaching and practice of epidemiology. The proposed concepts and methods are useful for particular problems, but it would be of concern if the theory and practice of the complete field of epidemiology were to become restricted to this single approach to causal inference. Our concerns are that this theory restricts the questions that epidemiologists may ask and the study designs that they may consider. It also restricts the evidence that may be considered acceptable to assess causality, and thereby the evidence that may be considered acceptable for scientific and public health decision making. These restrictions are based on a particular conceptual framework for thinking about causality. In Section 1, we describe the characteristics of the restricted potential outcomes approach (RPOA) and show that there is a methodological movement which advocates these principles, not just for solving particular problems, but as ideals for which epidemiology as a whole should strive. In Section 2, we seek to show that the limitation of epidemiology to one particular view of the nature of causality is problematic. In Section 3, we argue that the RPOA is also problematic with regard to the assessment of causality. We argue that it threatens to restrict study design choice, to wrongly discredit the results of types of observational studies that have been very useful in the past and to damage the teaching of epidemiological reasoning. Finally, in Section 4 we set out what we regard as a more reasonable 'working hypothesis' as to the nature of causality and its assessment: pragmatic pluralism. PMID- 26800753 TI - A Cluster Analytic Approach To MMPI Profile Types. AB - Aims were to identify the profile types present in MMPI scale scores using Ward's hierarchical procedure and a nonhierarchical average linkage method. One data set consisted of the 35 code types developed by Gilberstadt-Duker and Marks-Seeman Haller. Another data set consisted of Lanyon's group profiles of 210 diagnostic classes. These profiles were subdivided into odd-even samples of 105. Analysis of the 35 code types disclosed four clusters by either procedure: neurotics, depressed psychotics, excited psychotics, and sociopaths. Analysis of the two Lanyon subsamples uncovered several normal subgroups as well as the clusters found among the code types. These results indicate that a relatively small number of homogeneous subtypes can account for most code types and diagnostic group profiles. PMID- 26800752 TI - Postprandial Studies Uncover Differing Effects on HDL Particles of Overt and Subclinical Hypothyroidism. AB - BACKGROUND: Overt hypothyroidism (OH) is associated with abnormal lipid metabolism and endothelial dysfunction under fasting conditions. The balance of evidence suggests similar but less marked abnormalities in subclinical hypothyroidism (SCH). There are few data regarding the metabolic and vascular effects of OH or SCH under postprandial conditions. METHODS: This was a cross sectional study, carried out in a teaching hospital. Subjects with OH (n = 21), SCH (n = 28), and controls (n = 44) matched for age, sex, and body mass index (BMI) were studied under fasting and postprandial conditions. Postprandial lipid metabolism with particular emphasis on intestinally derived lipoproteins, HDL cholesterol (HDL), and endothelial function were compared in subjects with OH and SCH who were matched for age, sex, and BMI. Apolipoprotein B48 (Apo B48), a measure of intestinally derived lipoprotein, was measured by enzyme-linked immunosorbent assay. HDL was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. Functional aspects of HDL were determined by monitoring the activities of cholesteryl-ester-transfer-protein (CETP) and lecithin-cholesterol acyl-transferase (LCAT). Systemic and HDL-associated inflammation was assessed by measuring serum-amyloid-A (SAA) levels. Endothelial function was assessed by flow mediated dilatation (FMD) of the brachial artery in response to hyperemia of the forearm. RESULTS: There were no significant between-group differences in LDL cholesterol or triglyceride concentration. Peak Apo B48 levels were greater in OH (p < 0.001) and SCH (p < 0.05) compared with control subjects. HDL area under the curve (AUC) was lower postprandially in SCH (p < 0.001) but not OH compared with control subjects. HDL2- and HDL3-associated CETP AUC was lower only in OH (p < 0.005) compared with controls. FMD was reduced in OH (p < 0.05) compared with SCH and controls postprandially. CONCLUSION: Postprandial lipoprotein and vascular abnormalities differ between OH and SCH. Although both are characterized by increased intestinally derived lipoprotein particles, HDL is reduced only in SCH. Maintained HDL in OH probably reflects reduced CETP activity, which was not observed in SCH. Postprandial endothelial dysfunction is abnormal only in OH, and this effect does not appear to reflect increased inflammation. PMID- 26800754 TI - Set Correlation As A General Multivariate Data-Analytic Method. AB - Set correlation is a multivariate generalization of multiple regression/correlation analysis that features the employment of overall measures of association interpretable as proportions of variance and the use of set partialled sets of variables, e.g. D.C with B.A. Partialling is a powerful device that may be used for statistical control and for representing non-linear and conditional (interactive) relationships, contrast functions, and the uniqueness of a variable or subset of variables. Generally, it offers a means for specifying functional components of sets. Since information in virtually any form can be represented as a set, partialled if necessary, the extension of partialling to sets of dependent variables makes it possible, within a single framework, to study relationships that are currently handled by diverse methods. Because of its flexibility and generality, beyond its capacity to handle the standard multivariate methods as special cases, set correlation offers some useful novel data-analytic techniques, among which are illustrated a hierarchical analysis of common and unique aspects of a battery, multivariate contrasts among outcomes, the multivariate analysis of partial variance, and contingency table analysis. PMID- 26800755 TI - The Use Of Analysis Of Covariance Structures To Assess Beta And Gamma Change. AB - Detection of alpha, beta, and gamma change in assessments of organizational intervention have been problematic because of lack of clear definition of beta and gamma change and/or methods to assess such change. The present paper applies an analysis of covariance structures to this problem using pre and post employment responses to a questionnaire assessing human needs. An analysis of data transformed in a manner consistent with theoretical definitions of beta change indicated the presence of such change and further supported the use of the procedure. PMID- 26800756 TI - Assessing The Discriminant Validity Of Regression Models And Subjectively Weighted Models Of Judgments. AB - When either regression models or subjectively weighted models are used as aids in making placement decisions, the discriminant validity of these models is of interest. When all predictor information is used in all decisions, models which assign equal weights cannot simultaneously show high levels of predictive accuracy and discriminant validity; in some settings, both regression models and subjectively weighted models may. The discriminant validity of regression models and of subjectively weighted models was investigated in two judgment experiments. Both types of models showed high levels of accuracy and cross-validity in both experiments. Regression models showed discriminant validity in both experiments, while subjectively weighted models failed to show discriminant validity in the second. The homogeneity of cue validities appeared to moderate both the level of discriminant validity and the relationship between similarity of subjective models, across tasks, and discriminant validity. PMID- 26800757 TI - A Comparison Of Component And Factor Patterns: A Monte Carlo Approach. AB - Factor analysis and component analysis represent two broad classes of methods employed generally with similar types of problems. The purpose of the present study is to determine the extent to which and under what conditions the methods produce different patterns. Principal component analysis, image component analysis, and maximum likelihood factor analysis were performed on simulated data matrices. Comparisons were made between each of the three methods and to ideal patterns. Sample size, saturation, and type of pattern were systematically varied. The general conclusion reached is that the three methods produce results that are equivalent. In addition, several important trends were observed. PMID- 26800758 TI - A Taxometric Model For The Detection Of A Conjectured Latent Taxon. AB - A taxometric model is developed for testing the existence of an underlying dichotomous taxonomy consisting of a 'taxon' and its complement. The model includes procedures for estimation of the base rate of the taxon and the valid positive and false positive rates for each indicator of the taxon. The model also includes tests (referred to as "consistency tests") for checking the internal validity and the goodness of fit of the model to the data. In an illustrative application, responses to interview questions were used as candidate indicators of a conjectured taxon of dementia in a sample of 841 New York City and London older people. In this application consistency tests indicated the existence of a taxon, since the fit of the model was extraordinarily good. Strong agreement of the taxometric classification with a clinical diagnosis of dementia based on a review of a case summary provided favorable evidence for the construct validity of the taxon. PMID- 26800759 TI - The Study Of Effects In Manova. AB - A particular strategy for investigating effects resulting from a MANOVA is proposed. The strategy involves multiple two-group multivariate analyses. The two groups result from considering multivariate pairwise group contrasts or multivariate complex group contrasts. Assuming a given two-group analysis yields real effects, the resultant single linear discriminant function (LDF) may be studied. A rationale based on a transformation of LDF weights, due to V. Y. Urbakh, is recommended for assessing variable relative contribution. The analysis strategy is described in detail and illustrated with real data sets. PMID- 26800761 TI - Ionic Liquid Character of Zinc Chloride Hydrates Define Solvent Characteristics that Afford the Solubility of Cellulose. AB - The recently described ionic liquid structure of the three equivalent hydrate of zinc chloride (ZnCl2.R H2O, R = 3, existing as [Zn(OH2)6][ZnCl4]) explains the solubility of cellulose in this medium. Only hydrate compositions in the narrow range of 3 - x < R < 3 + x with x ~ 1 dissolve cellulose. Once dissolved, the cellulose remains in solution up to the R = 9 hydrate. Neutron diffraction and differential pair distribution function analysis of cellulose and model compound solutions (1 wt % cellulose in the R = 3 hydrate and 1 wt % ethanol in the R = 3 hydrate and the ZnCl2.3 ethanol liquid) coupled with detailed solubility measurements suggest that cellulose solubility occurs via coordination of the primary OH to the hydrated zinc cation with ring hydroxyls forming part of a second coordination shell around the cation of the ionic liquid. PMID- 26800762 TI - Versatile Miniature Tunable Liquid Lenses Using Transparent Graphene Electrodes. AB - This paper presents, for the first time, versatile and low-cost miniature liquid lenses with graphene as electrodes. Tunable focal length is achieved by changing the droplet curvature using electrowetting on dielectric (EWOD). Ionic liquid and KCl solution are utilized as lens liquid on the top of a flexible Teflon-coated PDMS/parylene membrane. Transparent and flexible, graphene allows transmission of visible light as well as large deformation of the polymer membrane to achieve requirements for different lens designs and to increase the field of view without damaging of electrodes. The tunable range for the focal length is between 3 and 7 mm for a droplet with a volume of 3 MUL. The visualization of bone marrow dendritic cells is demonstrated by the liquid lens system with a high resolution (456 lp/mm). PMID- 26800763 TI - Harmonizing the International Normalized Ratio (INR) : Standardization of Methods and Use of Novel Strategies to Reduce Interlaboratory Variation and Bias. AB - OBJECTIVES: To reduce interlaboratory variation and bias in international normalized ratio (INR) results, as used to monitor patients receiving vitamin K antagonist therapy, including warfarin, in a large pathology network (n = 27 laboratories) by procedural standardization and harmonization. METHODS: Network consensus to standardize to common instrument and reagent platforms was established, following development of hemostasis test specifications. Subsequent installations and implementation occurred after conclusion of a government tender process. Network-wide application of simple novel process of verification harmonization of local international sensitive index and mean normal prothrombin time initiated for each new lot of INR reagent that does not require ongoing use of reference thromboplastin or calibration/certified plasma sets. RESULTS: We achieved reduction of different instrument manufacturers (from four to one), instrument types (10 to three), reagent types (four to one), and instrument/reagent combinations (12 to three), plus substantial reduction in INR variability and bias. CONCLUSIONS: Results infer significant improvement in local patient management, with positive implications for other laboratories. For the United States in particular, lack of US Food and Drug Administration-cleared certified plasmas may compromise INR accuracy, and our novel approach may provide a workable alternative for laboratories and networks. PMID- 26800765 TI - Disseminated Acanthamoeba Infection Presenting With Cutaneous Lesions in an Immunocompromised Patient: A Case Report, Review of Histomorphologic Findings, and Potential Diagnostic Pitfalls. AB - OBJECTIVES: Free-living amoebas are exceedingly rare causes of cutaneous infections and present unique diagnostic and therapeutic challenges. We describe a case of disseminated acanthamoebiasis with cutaneous manifestations and summarize additional diagnostic, prognostic, and therapeutic highlights. METHODS: A 58-year-old man with relapsed chronic lymphocytic leukemia had several weeks of progressive, painful ulcerations on the forehead, arms, abdomen, and thighs. A biopsy was performed for histopathologic evaluation. RESULTS: The biopsy specimen showed inflammatory infiltrate with abscess formation involving the epidermis, dermis, and subcutis. Scattered cells showed nuclei with a prominent central karyosome, dispersed chromatin, and either abundant foamy basophilic cytoplasm or two well-demarcated cytoplasmic walls. Acanthamoeba species was confirmed by polymerase chain reaction from the formalin-fixed, paraffin-embedded tissue. CONCLUSIONS: Cutaneous lesions from acanthamoebiasis are exceptionally rare but should be included in the differential diagnosis of necrotic cutaneous lesions in immunocompromised patients. Although infrequently encountered, pathologists need to be aware of the morphologic features of free-living amoebas. Immunohistochemical and molecular studies can confirm the diagnosis. Multiagent treatment regimens, when initiated empirically, have been more successful than single-agent regimens, but infections involving the central nervous system are almost universally fatal. PMID- 26800764 TI - Detection of an Abnormal Myeloid Clone by Flow Cytometry in Familial Platelet Disorder With Propensity to Myeloid Malignancy. AB - OBJECTIVES: To report aberrant myeloblasts detected by flow cytometry immunophenotypic studies in an asymptomatic patient with familial platelet disorder with propensity to myeloid malignancy, a rare autosomal dominant disease caused by germline heterozygous mutations in Runt-related transcription factor 1. METHODS: Morphologic evaluation, flow cytometry immunophenotypic studies, nanofluidics-based qualitative multiplex reverse transcriptase polymerase chain reaction, Sanger sequencing, and next-generation sequencing-based mutational hotspot analysis of 53 genes were performed on bone marrow biopsy and aspirate samples. RESULTS: Flow cytometry immunophenotypic analysis showed 0.6% CD34+ blasts with an abnormal immunophenotype: CD13 increased, CD33+, CD38 decreased, CD117 increased, and CD123 increased. CONCLUSIONS: The acquisition of new phenotypic aberrancies in myeloblasts as detected by flow cytometry immunophenotypic studies might be a harbinger of impending myelodysplastic syndrome or acute myeloid leukemia in a patient with familial platelet disorder with propensity to myeloid malignancy. PMID- 26800766 TI - Evaluation of two local cowpea species for nutrient, antinutrient, and phytochemical compositions and organoleptic attributes of their wheat-based cookies. AB - BACKGROUND: Childhood and adolescent malnutrition is a function of inadequate intake. Cookies are favourite snacks of children and adolescents. OBJECTIVE: This work determined the nutrient, antinutrient, and phytochemical compositions of two local cowpea (oraludi and apama) flours and evaluated the organoleptic properties of their wheat-based cookies. DESIGN: The two local cowpea species were processed into flours separately and blended with wheat on a 56-g protein basis. Chemical compositions of the processed cowpea flours were analysed using standard methods. Organoleptic attributes were evaluated with a nine-point Hedonic scale. Statistical analysis, which involved mean and standard deviations, were computed by analysis of variance, and Duncan's new multiple range tests were used to separate and compare group means of sensory evaluation data, with significance accepted at P<0.05. RESULTS: The results revealed that oraludi had superior percentage values compared to apama in protein (26.22 and 20.88), fat (7.98 and 6.65), and ash (3.81 and 3.13), while apama proved superior in moisture (9.76 and 7.82), crude fibre (5.49 and 4.91), and carbohydrate (54.09 and 49.26). The values were higher for oraludi than apama in iron (8.62 and 6.49 mg), zinc (1.61 and 0.95 mg), and beta-carotene (223.24 and 190.63 mg) but lower in sodium (34.79 and 56.72 mg), potassium (25.73 and 30.65 mg), phosphorus (13.35 and 18.26 mg), thiamine (5.33 and 9.41 mg), vitamin C (16.63 and 21.09 mg), and vitamin E (0.51 and 0.67 mg). Apama had 0.06 mg phytate, 0.09 mg oxalate, 15.22 mg tannins, 3.59 mg flavonoids, and 0.19 mg saponin. Oraludi had 0.03 mg phytate, 0.32 mg oxalate, 15.94 mg tannins, 3.14 mg flavonoid, and 0.13 mg saponin. Mean scores of general acceptability for wheat:apama (80:20) and wheat:oraludi:apama (60:20:20) cookies (7.71 and 7.41) were superior (P<0.05) to others. CONCLUSIONS: Oraludi and apama proved nutrient dense. Their use improved the acceptability of some of the wheat based cookies. Use of these local cowpeas in cookie production is, therefore, encouraged. PMID- 26800767 TI - Changes in right ventricular function in neonates with hypoplastic left heart syndrome before and after the hybrid procedure. AB - AIMS: Decreased right ventricular function via deformation analysis has been noted in patients with hypoplastic left heart syndrome (HLHS) after the Norwood procedure. No data exist in HLHS patients undergoing the hybrid procedure. The goal of this study was to evaluate right ventricular functional changes in HLHS patients undergoing the hybrid procedure under steady-state conditions. METHODS AND RESULTS: Echocardiograms were prospectively obtained on patients with HLHS before and after the hybrid procedure. Fractional area change, tricuspid inflow velocities, tissue Doppler imaging (TDI), and deformation analysis were performed. Paired Wilcoxon's signed rank or Student's t-test was used for analysis. P < 0.05 was considered significant. Twenty HLHS patients were studied (10 males:10 females). Median age at the pre-hybrid echocardiogram was 3 (1-16) days, age at hybrid procedure was 5 (3-17) days, and age at post-hybrid echocardiogram was 10 (6-34). There were significant decreases in systolic function as measured by TDI and deformation analysis. There was no significant change in right ventricular fractional area change. Diastolic function was also noted to significantly decrease after the hybrid procedure. CONCLUSION: Systolic and diastolic functions decreased after the hybrid procedure despite the fact that patients avoided cardiopulmonary bypass. These results are comparable with previous reports in HLHS patients undergoing the Norwood procedure. Further studies are needed to determine if these echocardiographic changes have prognostic significance. PMID- 26800768 TI - Targeting of vascular cell adhesion molecule-1 by 18F-labelled nanobodies for PET/CT imaging of inflamed atherosclerotic plaques. AB - AIMS: Positron emission tomography-computed tomography (PET-CT) is a highly sensitive clinical molecular imaging modality to study atherosclerotic plaque biology. Therefore, we sought to develop a new PET tracer, targeting vascular cell adhesion molecule (VCAM)-1 and validate it in a murine atherosclerotic model as a potential agent to detect atherosclerotic plaque inflammation. METHODS AND RESULTS: The anti-VCAM-1 nanobody (Nb) (cAbVCAM-1-5) was radiolabelled with Fluorine-18 ((18)F), with a radiochemical purity of >98%. In vitro cell-binding studies showed specific binding of the tracer to VCAM-1 expressing cells. In vivo PET/CT imaging of ApoE(-/-) mice fed a Western diet or control mice was performed at 2h30 post-injection of [(18)F]-FB-cAbVCAM-1-5 or (18)F-control Nb. Additionally, plaque uptake in different aorta segments was evaluated ex vivo based on extent of atherosclerosis. Atherosclerotic lesions in the aortic arch of ApoE(-/-) mice, injected with [(18)F]-FB-anti-VCAM-1 Nb, were successfully identified using PET/CT imaging, while background signal was observed in the control groups. These results were confirmed by ex vivo analyses where uptake of [(18)F]-FB-cAbVCAM-1-5 in atherosclerotic lesions was significantly higher compared with control groups. Moreover, uptake increased with the increasing extent of atherosclerosis (Score 0: 0.68 +/- 0.10, Score 1: 1.18 +/- 0.36, Score 2: 1.49 +/- 0.37, Score 3: 1.48 +/- 0.38%ID/g, Spearman's r(2) = 0.675, P < 0.0001). High lesion-to-heart, lesion-to-blood, and lesion-to-control vessel ratios were obtained (12.4 +/- 0.4, 3.3 +/- 0.4, and 3.1 +/- 0.6, respectively). CONCLUSION: The [(18)F]-FB-anti-VCAM-1 Nb, cross-reactive for both mouse and human VCAM-1, allows non-invasive PET/CT imaging of VCAM-1 expression in atherosclerotic plaques in a murine model and may represent an attractive tool for imaging vulnerable atherosclerotic plaques in patients. PMID- 26800769 TI - Morphological predictors for no reflow phenomenon after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction caused by plaque rupture. AB - AIMS: Myocardial no reflow after percutaneous coronary intervention (PCI) is associated with poor outcome. Patients with ST-segment elevation myocardial infarction (STEMI) caused by plaque rupture are at high risk for no reflow. However, specific morphologic characteristics associated with no reflow are unknown in this population. The aim of this study is to identify the morphological characteristics of culprit plaques associated with no reflow in patients with STEMI caused by plaque rupture using both optical coherence tomography (OCT) and intravascular ultrasound (IVUS). METHODS AND RESULTS: We enrolled 145 patients with STEMI who underwent both OCT and IVUS within 12 h of symptom onset. Among these patients, we excluded those with plaque erosion and calcified nodule and included 72 patients who had plaque rupture as an underlying mechanism for STEMI. Myocardial no reflow, defined as Thrombolysis in Myocardial Infarction flow grade 0-2 and/or myocardial blush grade 0-1 after PCI, was observed in 28 patients (38.9%). Onset to recanalization time was similar between the groups with and without no reflow. Receiver-operating curve analysis revealed OCT-derived lipid index > 3500 [area under curve (AUC) 0.77, P < 0.001] and IVUS derived plaque burden > 81.5% (AUC 0.70, P = 0.002) were the best discriminators for myocardial no reflow. CONCLUSION: No reflow occurred in nearly 40% of patients with STEMI caused by plaque rupture. Large lipid index and plaque burden were critical morphological discriminators between no reflow and normal flow. PMID- 26800770 TI - Large lipid-rich coronary plaques detected by near-infrared spectroscopy at non stented sites in the target artery identify patients likely to experience future major adverse cardiovascular events. AB - AIMS: A recent study demonstrated that intracoronary near-infrared spectroscopy (NIRS) findings in non-target vessels are associated with major adverse cardiovascular and cerebrovascular events (MACCE). It is unknown whether NIRS findings at non-stented sites in target vessels are similarly associated with future MACCE. This study evaluated the association between large lipid-rich plaques (LRP) detected by NIRS at non-stented sites in a target artery and subsequent MACCE. METHODS AND RESULTS: This study evaluated 121 consecutive registry patients undergoing NIRS imaging in a target artery. After excluding stented segments, target arteries were evaluated for a large LRP, defined as a maximum lipid core burden index in 4 mm (maxLCBI4 mm) >=400. Excluding events in stented segments, Cox regression analysis was performed to evaluate for an association between a maxLCBI4 mm >=400 and future MACCE, defined as all-cause mortality, non-fatal acute coronary syndrome, and cerebrovascular events. NIRS detected a maxLCBI4 mm >=400 in a non-stented segment of the target artery in 17.4% of patients. The only baseline clinical variable marginally associated with MACCE was ejection fraction (HR 0.96, 95% CI 0.93-1.00, P = 0.054). A maxLCBI4 mm >=400 in a non-stented segment at baseline was significantly associated with MACCE during follow-up (HR 10.2, 95% CI 3.4-30.6, P < 0.001). CONCLUSION: Detection of large LRP by NIRS at non-stented sites in a target artery was associated with an increased risk of future MACCE. These findings support ongoing prospective studies to further evaluate the ability of NIRS to identify vulnerable patients. PMID- 26800771 TI - Using postoperative SNOT-22 to help predict the probability of revision sinus surgery. AB - BACKGROUND: There is a need to develop a patient-level strategy to identify those at higher risk of requiring revision ESS since this may assist clinicians in tailoring their postoperative management. This study evaluated whether identifying changes in the post- operative 22-item Sinonasal Outcome Test (SNOT 22) can help identify patients at increased risk of needing revision sinus surgery for refractory chronic rhinosinusitis (CRS). METHODS: 668 CRS patients undergoing primary ESS with complete 60-month follow-up were evaluated in this prospective, longitudinal cohort study. Outcomes were evaluated in an unselected cohort and a low-risk cohort, which was comprised of patients without a history of asthma or aspirin sensitivity. RESULTS: Failing to achieve an improvement of greater than one minimal clinically important difference (MCID; 9 points) at 3 months after primary ESS and a deterioration of greater than one MCID (ie. >9 points) from the 3- to 12-month follow-up periods was associated with an increased risk of revision ESS in both the unselected and low-risk CRS cohorts. CONCLUSION: Outcomes from this study suggest that identifying MCID changes in the SNOT-22 score within 12 months after primary ESS can identify patients at increased risk for needing revision surgery. PMID- 26800773 TI - Frequency of Massive Cardiac Adiposity (Floating Heart) at Necropsy and Comparison of Clinical and Morphologic Variables With Cases With Nonmassive Cardiac Adiposity at a Single Texas Hospital, 2013 to 2014. AB - Body weight continues to increase worldwide primarily because of the increase in body fat. This study analyzes the frequency of massive adiposity at autopsy determined by the ability of the heart to float in a container of 10% formaldehyde (because adipose tissue is lighter than myocardium) and compares certain findings in the patients with floating to those with nonfloating hearts. The hearts studied at necropsy during a 2-year period (2013 to 2014) at Baylor University Medical Center were carefully "cleaned" and weighed by the same person and tested as to their ability to float in a container of formaldehyde, an indication of severe cardiac adiposity. Of the 146 hearts studied, 76 (52%) floated in a container of formaldehyde and 70 (48%) did not. Comparison of the 76 patients with floating hearts with the 70 with nonfloating hearts showed significant differences in ages (62 +/- 13 vs 58 +/- 14 years). No significant differences between the 2 groups were found in gender, body mass index, frequency of systemic hypertension or diabetes mellitus, either acute or healed myocardial infarction, or whether death was due to a coronary or a noncoronary condition. A weak correlation was found between body mass index and heart weight in both men and women and in both floating and nonfloating hearts. The massive quantity of cardiac adipose tissue (floating heart) appears to have increased enormously in recent decades in the United States. PMID- 26800772 TI - Predicting the risk of malignancy in adnexal masses based on the Simple Rules from the International Ovarian Tumor Analysis group. AB - BACKGROUND: Accurate methods to preoperatively characterize adnexal tumors are pivotal for optimal patient management. A recent metaanalysis concluded that the International Ovarian Tumor Analysis algorithms such as the Simple Rules are the best approaches to preoperatively classify adnexal masses as benign or malignant. OBJECTIVE: We sought to develop and validate a model to predict the risk of malignancy in adnexal masses using the ultrasound features in the Simple Rules. STUDY DESIGN: This was an international cross-sectional cohort study involving 22 oncology centers, referral centers for ultrasonography, and general hospitals. We included consecutive patients with an adnexal tumor who underwent a standardized transvaginal ultrasound examination and were selected for surgery. Data on 5020 patients were recorded in 3 phases from 2002 through 2012. The 5 Simple Rules features indicative of a benign tumor (B-features) and the 5 features indicative of malignancy (M-features) are based on the presence of ascites, tumor morphology, and degree of vascularity at ultrasonography. Gold standard was the histopathologic diagnosis of the adnexal mass (pathologist blinded to ultrasound findings). Logistic regression analysis was used to estimate the risk of malignancy based on the 10 ultrasound features and type of center. The diagnostic performance was evaluated by area under the receiver operating characteristic curve, sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive predictive value (PPV), negative predictive value (NPV), and calibration curves. RESULTS: Data on 4848 patients were analyzed. The malignancy rate was 43% (1402/3263) in oncology centers and 17% (263/1585) in other centers. The area under the receiver operating characteristic curve on validation data was very similar in oncology centers (0.917; 95% confidence interval, 0.901-0.931) and other centers (0.916; 95% confidence interval, 0.873-0.945). Risk estimates showed good calibration. In all, 23% of patients in the validation data set had a very low estimated risk (<1%) and 48% had a high estimated risk (>=30%). For the 1% risk cutoff, sensitivity was 99.7%, specificity 33.7%, LR+ 1.5, LR- 0.010, PPV 44.8%, and NPV 98.9%. For the 30% risk cutoff, sensitivity was 89.0%, specificity 84.7%, LR+ 5.8, LR- 0.13, PPV 75.4%, and NPV 93.9%. CONCLUSION: Quantification of the risk of malignancy based on the Simple Rules has good diagnostic performance both in oncology centers and other centers. A simple classification based on these risk estimates may form the basis of a clinical management system. Patients with a high risk may benefit from surgery by a gynecological oncologist, while patients with a lower risk may be managed locally. PMID- 26800774 TI - Relation of Adiponectin to All-Cause Mortality, Cardiovascular Mortality, and Major Adverse Cardiovascular Events (from the Dallas Heart Study). AB - Adiponectin is a key component in multiple metabolic pathways. Studies evaluating associations of adiponectin with clinical outcomes in older adults have reported conflicting results. We investigated the association of adiponectin with mortality and cardiovascular disease (CVD) morbidity in a young, multiethnic adult population. We analyzed data from participants in the Dallas Heart Study without baseline CVD who underwent assessment of total adiponectin from 2000 to 2002. The primary outcome of all-cause mortality was assessed over median 10.4 years of follow-up using multivariable-adjusted Cox proportional hazards models. Secondary outcomes included CVD mortality, major adverse cardiovascular and cerebrovascular events (MACCE), and heart failure (HF). The study cohort included 3,263 participants, mean age 43.4 years, 44% women, and 50% black. There were 184 deaths (63 CVD), 207 MACCE, and 46 HF events. In multivariable models adjusted for age, gender, race, hypertension, diabetes, smoking, high-density lipoprotein cholesterol-C, hyperlipidemia, high-sensitivity C-reactive protein level, estimated glomerular filtration rate, and body mass index, increasing adiponectin quartiles were positively associated with all-cause mortality Q4 versus Q1 (hazard ratio [HR] = 2.27; 95% confidence interval [CI] 1.47, 3.50); CVD mortality Q4 versus Q1 (HR = 2.43; 95% CI 1.15, 5.15); MACCE Q4 versus Q1 (HR = 1.71; 95% CI 1.13, 2.60); and HF Q4 versus Q1 (HR = 2.95; 95% CI 1.14, 7.67). Findings were similar with adiponectin as a continuous variable and consistent across subgroups defined by age, gender, race, obesity, diabetes, metabolic syndrome, or elevated high-sensitivity C-reactive protein. In conclusion, higher adiponectin was associated with increased mortality and CVD morbidity in a young, multiethnic population. These findings may have implications for strategies aimed at lowering adiponectin to prevent adverse outcomes. PMID- 26800775 TI - Production of pseudorabies virus recombinant glycoprotein B and its use in an agar gel immunodiffusion (AGID) test for detection of antibodies with sensitivity and specificity equal to the virus neutralization assay. AB - Pseudorabies virus (PrV) causes Aujeszky's disease (AD), which affects mainly swine, but also cattle, sheep, and wild animals, resulting in substantial economic losses due to animal mortality and lost productivity worldwide. To combat PrV, eradication programs using PrV strains lacking the gene encoding glycoprotein E (gE) are ongoing in several countries. These eradication programs have generated a currently unmet demand for affordable, easy-to-use, and sensitive tests that can detect PrV infection in pigs infected with either wild type virus or vaccine strain (gE-deleted) virus. To meet this demand, we used the baculovirus-insect cell system to produce recombinant glycoprotein B (gB) as antigen for an immune assay. The high GC-content (70% average) of the gB gene from the Argentinian PrV CL15 strain necessitated the use of betaine as a PCR enhancer to amplify the extracellular domain. Recombinant gB was expressed at high levels and reacted strongly with sera from PrV infected pigs. We used the recombinant gB to develop an agar gel immunodiffusion (AGID) test for detection of PrV antibodies. Compared to the gold standard virus neutralization (VN) assay, the AGID sensitivity and specificity were 95% and 96.6% respectively. Thus, recombinant gB produced in the baculovirus-insect cell system is a viable source of antigen for the detection of PrV antibodies in AGID tests. Considering its relatively lower cost, simplicity of use and result interpretation, our AGID is a valuable alternative tool to the VN assay. PMID- 26800776 TI - Construction of a subgenomic CV-B3 replicon expressing emerald green fluorescent protein to assess viral replication of a cardiotropic enterovirus strain in cultured human cells. AB - Coxsackieviruses B (CV-B) (Picornaviridae) are a common infectious cause of acute myocarditis in children and young adults, a disease, which is a precursor to 10 20% of chronic myocarditis and dilated cardiomyopathy (DCM) cases. The mechanisms involved in the disease progression from acute to chronic myocarditis phase and toward the DCM clinical stage are not fully understood but are influenced by both viral and host factors. Subgenomic replicons of CV-B can be used to assess viral replication mechanisms in human cardiac cells and evaluate the effects of potential antiviral drugs on viral replication activities. Our objectives were to generate a reporter replicon from a cardiotropic prototype CV-B3/28 strain and to characterize its replication properties into human cardiac primary cells. To obtain this replicon, a cDNA plasmid containing the full CV-B3/28 genome flanked by a hammerhead ribozyme sequence and an MluI restriction site was generated and used as a platform for the insertion of sequences encoding emerald green fluorescent protein (EmGFP) in place of those encoding VP3. In vitro transcribed RNA from this plasmid was transfected into HeLa cells and human primary cardiac cells and was able to produce EmGFP and VP1-containing polypeptides. Moreover, non-structural protein biological activity was assessed by the specific cleavage of eIF4G1 by viral 2A(pro). Viral RNA replication was indirectly demonstrated by inhibition assays, fluoxetine was added to cell culture and prevented the EmGFP synthesis. Our results indicated that the EmGFP CV-B3 replicon was able to replicate and translate as well as the CV-B3/28 prototype strain. Our EmGFP CV-B3 replicon will be a valuable tool to readily investigate CV-B3 replication activities in human target cell models. PMID- 26800777 TI - Detection of Puumala virus in the tissue of infected naturally rodent hosts in the area of central Dinarides. AB - Hantaviruses are the causative agents of haemorrhagic fever with renal syndrome (HFRS) in Euroasia and of hantavirus cardiopulmonary syndrome (HCPS) in the North, Central and South America. HFRS is endemic in the Balkan Peninsula, where sporadic cases or outbreaks have been reported. Puumala virus (PUUV) is the causative agent of nephropathia epidemica (NE), a mild form of HFRS. PUUV is carried by the bank voles (Myodes glareolus). In this study, we investigated viral RNA from 76 tissues samples (lung n=30, heart n=6, liver n=18 and kidney n=22) of infected naturally rodent hosts in the area of Central Dinarides caught in live traps. Puumala virus was extracted from 34,7% (16/46) rodents by nested reverse transcriptase polymerase chain reaction (RT-PCR) and real-time RT-PCR. Overall, 18 (21,4%) specimens of internal organs (kidney n=8, liver n=6, heart n=2 and lung n=2) were positive for PUUV. It was shown a high rodent infestation rate in a relatively low number of rodent and their organs, although mice were not caught during the time of high density population of host rodents. PMID- 26800778 TI - Cytokine-based immune monitoring. AB - Several studies conducted during the last decade have shown that some promising biomarkers and surrogate markers may be useful in implementing personalized immunomodulatory therapies and improving graft and recipient care in solid organ transplantation. The complexity of the immune system response against the implanted graft can change remarkably in the long-term follow-up, and the dynamic balance between T-effector/T-regulatory cell populations determines the outcome of the anti-donor response, risk of rejection, and immunosuppression requirements. For this reason, at any time before and after transplantation, monitoring the T-effector cell activity, associated with an increase in pro inflammatory cytokine production and release, can be considered as a surrogate marker of the risk of rejection and immunosuppression requirements. Furthermore, infections remain a cause of major complications following transplantation, highlighting the need for developing new approaches aimed at identifying the risk of infection in solid organ recipients. Another main aspect to be considered is that immunosuppressive agents may immunomodulate each treated patient differently. Immunosuppressive drugs show high pharmacokinetic and pharmacodynamic inter-patient variability. Some pharmacodynamic biomarkers such as measurement of the inhibition of target activity can reflect the individual's susceptibility to the treatment. Monitoring a panel of valid biomarkers may provide patient stratification and better immunosuppression treatment selection. After transplantation, therapy should be adjusted based on the prediction of rejection episodes (maintained alloreactivity), prognosis of allograft damage progression, and personal drug response. This review focuses on current knowledge, indicating that monitoring T-cell changes in the production of cytokines such as interferon gamma (IFN-gamma) and interleukin (IL)-2, and also the expression of IL-17 by central and effector memory T cells, could be used to predict the risk of rejection and infection, thereby guiding immunosuppressive therapy in transplant recipients. PMID- 26800779 TI - Decreased sensitivity of the automatic white precursor cell channel (WPC) for blast flagging in patients with leukopenia. AB - OBJECTIVES: The advantage of Sysmex XN system is its performance of an automatic reflex test in white cell precursor (WPC) channel, which gives an accurate differential count. We performed a real-time evaluation of the automatic differential count according to WBC number with Sysmex XN series and demonstrated a significant differential impact on blast distinction depending on the number of WBC. DESIGN AND METHODS: We categorized the 49,699 specimen according to WBC number and compared the results of blast flagging in the white cell differential (WDF) channel and WPC channel on the basis of the results of manual differential count. Additionally, clinical impact of missed blasts after running WPC reflex test was analyzed. RESULTS: For patients with WBC under 1.5*10(9)/L, blast flagging for WPC channel showed markedly decreased sensitivity (56%) compared to that of WDF mode (100%). Most of the patients with missed blasts in WPC mode were under chemotherapy or hematopoietic stem cell transplantation. The specificity and efficiency for WPC channel were much higher than that of WDF mode in all range of WBC. CONCLUSIONS: Considering the additional reagent cost required for the WPC channel, WPC reflex test is not suitable for patients with leukopenia if it is operated alone. Instead, manual blood film review or double-check with other supplemental equipment should be accompanied. PMID- 26800780 TI - A simple matrix of analytical performance to identify assays that risk patients using External Quality Assurance Program data. AB - OBJECTIVES: We propose a simple way to reliably rank assays for improvement according to patient risk, based solely on EQA imprecision and biological variation data. Because the underlying technique aligns the imprecision class of an assay from EQA data, peer performance can be used to assess achievable imprecision and the risk ranking can not only prioritise improvement but also highlight laboratory QC operating parameters that are easy to manage and provide reliable, acceptable performance. DESIGN AND METHODS: A modified Failure Modes Effects Analysis (FMEA) is applied to produce an analyte risk rating based on three factors, each of which is graded: 1) the ease of detecting analytical errors based on the ratio of allowable limits of performance to imprecision (Assay Capability) compared to absolute standards and to peers, 2) the predicted frequency of errors in patient monitoring based on the ratio of within-individual biological variation to laboratory imprecision, and 3) the clinical importance of the assay as a surrogate marker for harm arising from an error. RESULTS: We provide laboratory examples to illustrate these models. CONCLUSION: The proposed models using only EQA data can objectively identify assays at risk of failing against biological variation goals for monitoring patients and suggest parameters for reliable performance. PMID- 26800781 TI - Intra-operative parathyroid hormone monitoring through central laboratory is accurate in renal secondary hyperparathyroidism. AB - OBJECTIVE: The usefulness, the methods and the criteria of intra-operative monitoring of the parathyroid hormone (ioPTH) during parathyroidectomy (PTX) for renal secondary hyperparathyroidism (rSHPT) in patients on chronic hemodialysis remain still matter of debate. The present study aimed to evaluate the ability of a low cost central-laboratory second generation PTH assay to predict an incomplete resection of parathyroid glands (PTG). METHODS: The ioPTH decay was determined In 42 consecutive patients undergoing PTX (15 subtotal and 27 total without auto-transplant of PTG) for rSHPT. The ioPTH monitoring included five samples: pre-intubation, post-manipulation of PTG and at 10, 20 and 30min post PTG excision. The patients with PTH exceeding the normal value (65pg/ml) at the first postoperative week, 6 and 12months were classified as persistent rSHPT. RESULTS: The concentrations of ioPTH declined significantly over time in patients who received total or subtotal PTX; however, no difference was found between the two types of PTX. Irrespective of the type of PTX and the number of PTG removed, combining the absolute and percentage of ioPTH decay at 30min after PTG excision, we found high sensitivity (100%), specificity (92%), negative predictive value (100%) and accuracy (93%) in predicting the persistence of rSHPT. CONCLUSIONS: The monitoring of the ioPTH decline by a low cost central-laboratory second generation assay is extremely accurate in predicting the persistence of disease in patients on maintenance hemodialysis undergoing surgery for rSHPT. PMID- 26800782 TI - The mitochondrial genome of Atrijuglans hetaohei Yang (Lepidoptera: Gelechioidea) and related phylogenetic analyses. AB - Complete mitochondrial genome sequences are of great importance for better understanding the genome-level characteristics and phylogenetic relationships among related species. In this study, the complete mitochondrial genome of Atrijuglans hetaohei Yang is sequenced and analyzed, which is 15,379bp in length (GenBank: KT581634) and contains a typical set of 13 protein-coding genes, 22 tRNA genes, two rRNA genes and a non-coding region (control region). Except for cox1 gene that is initiated by CGA codon, all protein-coding genes start with ATN codons and end with the stop codon T, TA or TAA. All tRNAs have a typical clover leaf secondary structure, except for trnS1, of which the DHU arm could not form a stable stem-loop structure. The secondary structure of rrnL and rrnS consists of 49 helices and 33 helices, respectively. Phylogenetic analyses of the complete mitochondrial genome sequences and of the amino acid sequences for 13 mitochondrial protein-coding genes among related species support the view that A. hetaohei is more closely related to the Gelechioidea than Yponomeutoidea. This result is consistent with a previous classification based on morphology. PMID- 26800784 TI - Tactile learning in rodents: Neurobiology and neuropharmacology. AB - Animal models of learning and memory have been the subject of considerable research. Rodents such as mice and rats are nocturnal animals with poor vision, and their survival depends on their sense of touch. Recent reports have shown that whisker somatosensation is the main channel through which rodents collect and process environmental information. This review describes tactile learning in rodents from a neurobiological and neuropharmacological perspective, and how this is involved in memory-related processes. PMID- 26800785 TI - Selective serotonin reuptake inhibitors increase sympathetic activity under heavy alcohol exposure in rat models. AB - AIMS: Self-medication with alcohol while being treated with antidepressants is a common problem in patients with depression. Both alcohol consumption and antidepressant administration can induce changes in the cardiac autonomic responses as indicated by heart rate variability (HRV). In this study, we examined cardiac autonomic responses induced by acute heavy alcohol exposure after SSRIs (selective serotonin reuptake inhibitors) medications. MAIN METHODS: Rats were randomly divided into 3 groups, the alcohol administrated (Alc group), paroxetine administrated (SSRI group), and the SSRI+Alc group. Serum samples were collected to measure blood alcohol concentration (BAC). Physiological and cardiac autonomic responses including mean arterial pressure (MAP), heart rate (HR), and HRV were also compared among groups. KEY FINDINGS: The SSRI group exhibited higher values of HRV and HF (high frequency) than did the Alc and SSRI+Alc groups after alcohol administration. In contrast to the Alc group, the SSRI+Alc group had significantly lower MAP than Alc group, and higher HR, standard deviation of NN-intervals (SDNN), SDNN to MRR ratio (CVNN), square root of the mean squared differences of the successive NN-intervals (RMSSD) and HF values after alcohol administration. SIGNIFICANCE: Our results indicate that SSRIs increased sympathetic activity and alcohol reduced it in rats. The present study represents an attractive area for further research. PMID- 26800786 TI - Unraveling the role of Mg(++) in osteoarthritis. AB - Mg(++) is widely involved in human physiological processes that may play key roles in the generation and progression of diseases. Osteoarthritis (OA) is a complex joint disorder characterized by articular cartilage degradation, abnormal mineralization and inflammation. Magnesium deficiency is considered to be a major risk factor for OA development and progression. Magnesium deficiency is active in several pathways that have been implicated in OA, including increased inflammatory mediators, cartilage damage, defective chondrocyte biosynthesis, aberrant calcification and a weakened effect of analgesics. Abundant in vitro and in vivo evidence in animal models now suggests that the nutritional supplementation or local infiltration of Mg(++) represent effective therapies for OA. The goal of this review is to summarize the current understanding of the role of Mg(++) in OA with particular emphasis on the related molecular mechanisms involved in OA progression. PMID- 26800787 TI - Lactate calcium salt affects the viability of colorectal cancer cells via betaine homeostasis. AB - AIMS: Betaine plays an important role in cellular homeostasis. However, the physiological roles of betaine-gamma-aminobutyric acid (GABA) transporter (BGT-1) are still being disputed in cancer. In this study, we tried to find the possibility of the antitumor effect on colorectal cancer (CRC) cell via lactate calcium salt (CaLa)-induced BGT-1 downregulation. MAIN METHODS: The CRC cell viability and clonogenic assay was performed using different doses of BGT-1 inhibitor. The expression level of BGT-1 was measured following the treatment of 2.5mM CaLa. Betaine was treated to confirm the resistance of the antitumor activity by CaLa. Tumor growth was also measured using a xenograft animal model. KEY FINDINGS: Long-term exposure of 2.5mM CaLa clearly decreased the expression of BGT-1 in the CRC cells. As a result of the downregulation of BGT-1 expression, the clonogenic ability of CRC cells was also decreased in the 2.5mM CaLa-treated group. Reversely, the number of colonies and cell viability was increased by combination treatment with betaine and 2.5mM CaLa, as compared with a single treatment of 2.5mM CaLa. Tumor growth was significantly inhibited in the xenograft model depending on BGT-1 downregulation by 2.5mM CaLa treatment. SIGNIFICANCE: These results support the idea that long-lasting calcium supplementation via CaLa contributes to disruption of betaine homeostasis in the CRC cells and is hypothesized to reduce the risk of CRC. In addition, it indicates the possibility of CaLa being a potential incorporating agent with existing therapeutics against CRC. PMID- 26800788 TI - Cannabinoid CB1 receptor inhibition blunts adolescent-typical increased binge alcohol and sucrose consumption in male C57BL/6J mice. AB - Increased binge alcohol consumption has been reported among adolescents as compared to adults in both humans and rodent models, and has been associated with serious long-term health consequences. However, the neurochemical mechanism for age differences in binge drinking between adolescents and adults has not been established. The present study was designed to evaluate the mechanistic role of the cannabinoid CB1 receptor in adolescent and adult binge drinking. Binge consumption was established in adolescent and adult male C57BL/6J mice by providing access to 20% alcohol or 1% sucrose for 4h every other day. Pretreatment with the CB1 antagonist/inverse agonist AM-251 (0, 1, 3, and 10mg/kg) in a Latin square design dose-dependently reduced adolescent alcohol consumption to adult levels without altering adult intake. AM-251 (3mg/kg) also reduced adolescent but not adult sucrose consumption. Adolescent reductions in alcohol and sucrose were not associated with alterations in open-field locomotor activity or thigmotaxis. These findings point to age differences in CB1 receptor activity as a functional mediator of adolescent-typical increased binge drinking as compared to adults. Developmental alterations in endocannabinoid signaling in the adolescent brain may therefore be responsible for the drinking phenotype seen in this age group. PMID- 26800789 TI - HEART Pathway Accelerated Diagnostic Protocol Implementation: Prospective Pre Post Interrupted Time Series Design and Methods. AB - BACKGROUND: Most patients presenting to US Emergency Departments (ED) with chest pain are hospitalized for comprehensive testing. These evaluations cost the US health system >$10 billion annually, but have a diagnostic yield for acute coronary syndrome (ACS) of <10%. The history/ECG/age/risk factors/troponin (HEART) Pathway is an accelerated diagnostic protocol (ADP), designed to improve care for patients with acute chest pain by identifying patients for early ED discharge. Prior efficacy studies demonstrate that the HEART Pathway safely reduces cardiac testing, while maintaining an acceptably low adverse event rate. OBJECTIVE: The purpose of this study is to determine the effectiveness of HEART Pathway ADP implementation within a health system. METHODS: This controlled before-after study will accrue adult patients with acute chest pain, but without ST-segment elevation myocardial infarction on electrocardiogram for two years and is expected to include approximately 10,000 patients. Outcomes measures include hospitalization rate, objective cardiac testing rates (stress testing and angiography), length of stay, and rates of recurrent cardiac care for participants. RESULTS: In pilot data, the HEART Pathway decreased hospitalizations by 21%, decreased hospital length (median of 12 hour reduction), without increasing adverse events or recurrent care. At the writing of this paper, data has been collected on >5000 patient encounters. The HEART Pathway has been fully integrated into health system electronic medical records, providing real-time decision support to our providers. CONCLUSIONS: We hypothesize that the HEART Pathway will safely reduce healthcare utilization. This study could provide a model for delivering high-value care to the 8-10 million US ED patients with acute chest pain each year. CLINICALTRIAL: Clinicaltrials.gov NCT02056964; https://clinicaltrials.gov/ct2/show/NCT02056964 (Archived by WebCite at http://www.webcitation.org/6ccajsgyu). PMID- 26800790 TI - Applicability, validation and reproducibility of the Spinal Cord Independence Measure version III (SCIM III) in patients with non-traumatic spinal cord lesions. AB - PURPOSE: To verify the applicability, reproducibility and validity of the SCIM III patients with non-traumatic spinal cord injury. METHOD: The cross-sectional study included 30 patients (66% females; 41.5 +/- 14.7 yo) with non-traumatic spinal cord injury of any etiology. Subjects were subjected by computerized gait analysis and answered the Brazilian versions of SCIM III (0-100 points) and FIMTM (18-126 points) by two raters (A and B) at the same day and 1 week later (A). RESULTS: The intraclass correlation coefficient for the use of SCIM III indicated appropriated intra- and inter-evaluator reproducibility (ICC = 0.9). Correlation between the SCIM III and the motor FIMTM was appropriate (r = 0.6; p = 0.0). SCIM III subscales and FIMTM domains correlated strongly for self-care (r = 0.8; p <= 0.001), moderately for transfers (r = 0.6; p = 0.0005) and locomotion (r = 0.6; p = 0.0006). SCIM III mobility subscale positively correlated with the cadence (r = 0.8; p <= 0.01), gait speed (r = 0.7; p <= 0.01) and step length (r = 0.6; p <= 0.01). CONCLUSIONS: SCIM III is a reproducible functional assessment instrument and capable of evaluating the level of independence of the individual with non traumatic spinal cord injury. The SCIM III is more sensitive than the MIFTM for non-traumatic spastic paraplegic patients with higher levels of independence, particularly if they can walk independently. Linear gait parameters correlated with its mobility subscale. Implications for Rehabilitation Applicability, validation and reproducibility of the Spinal Cord Independence Measure version III (SCIM III) in patients with non-traumatic spinal cord lesions. There are not many studies focused on patients with non-traumatic spinal cord lesion. Disability varies in severity, but frequently contributes to limitations in the activities of daily living (ADL) and participation. We do not find in the literature studies that assess the functionality of these individuals as comprehensive as ours. PMID- 26800839 TI - OBITUARY ON HELEN SELLS (1911-1984). PMID- 26800840 TI - A Latent Trait Analysis of the MMPI. AB - Commonly used techniques for analyzing the structure of the MMPI scales were discussed and the use of a latent trait model was suggested as an alternative. The items on each scale of the MMPI were calibrated using a discrimination statistic. The item calibration statistics obtained from a replication sample were highly correlated with those obtained in the first sample. Poor fitting items were identified, and possible reasons for poor fits were discussed. The scales generally had few poor fits. The poor fitting items were generally those identified by Wiener (1956) as comprising the "subtle" subscales of the test. PMID- 26800841 TI - Exact F Tests in an ANOVA Procedure for Dependent Observations. AB - Several general correlation patterns are shown in this paper which give exact F tests in an ANOVA procedure with dependent observations. This paper presents the most general correlation patterns one can assume in a one-way and two-way layout and still have the F tests be valid. Exact F tests are given for various designs. These include the unbalanced ANOVA design, analysis of covariance, random effects models, and mixed models. Bartlett's test for homogeneity of variances is shown to be exact when the independence assumption is relaxed. An example is provided to illustrate how the general correlation can occur in an experimental design. PMID- 26800842 TI - A Strategy for Reducing and Analyzing Ordered Choice Data. AB - A major barrier to use of new measurement methodologies in behavioral research has been the difficulties encountered in collecting individual judgements. Balanced incomplete block design (BIBD) procedures offer enormous flexibility in the way judgmental data may be collected. The advantages and disadvantages of BIBDs are clarified and their use is demonstrated with an empirical example. A procedure for reducing data of this type to analyzable form is proposed and an analytical approach that is appropriate for the resulting data is illustrated. PMID- 26800843 TI - A Probabilistic Latent Class Model for Assessing Inter-Judge Reliability. AB - Increasingly behavioral researchers are soliciting cognitive responses in addition to standard attitudinal measures when attempting to assess the effects of persuasive communications. The coding of the elicited cognitive responses generally involves some sort of categorization, typically undertaken by independent judges, and the quality of the data is, to a large degree, evaluated in terms of some reliability coefficient which reflects the extent to which the independent judges agreed. The purpose of this paper is to present and illustrate a probabilistic model for assessing inter-judge reliability. The proposed probabilistic model allows one to (a) use formal test statistics to evaluate the extent and character of inter-judge reliability, (b) estimate the assignment error rates and their standard errors, and (c) test for simultaneous agreement for more than two judges. The probabilistic model is operationalized in terms of restricted latent class models. PMID- 26800845 TI - Plasmatic proinflammatory chemokines levels are tricky markers to monitoring HTLV 1 carriers. AB - The human T-cell leukemia virus type 1 (HTLV-1) is present throughout the world and is associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other inflammatory conditions. The pathogenesis of HAM/TSP involves a chronic inflammatory response in central nervous system (CNS), with the presence of HTLV-1 infected cells and HTLV-1-specific CD8+ lymphocytes. Chemokines may have a role in the infiltration of these cells into the CNS. In this context, the present study analyzed the level of plasmatic chemokines CCL2 (MCP-1), CCL5 (RANTES), IL8 (CXCL8), CXCL9 (MIG), and CXCL10 (IP-10) and HTLV-1 proviral load from peripheral blood in 162 asymptomatic carriers and 136 HAM/TSP patients to determine the differences that be associated with the clinical status of the HTLV-1 infection. The results showed that patients with HAM/TSP have significantly higher levels of IL8 and CXCL9, and that the level of IL8, CXCL9 and CXCL10 was significantly greater in HTLV-1 infected individuals with high (>1%) than those with low proviral load (<1%). However, the levels of the chemokines tested have not showed high sensitivity to discriminate HAM/TSP patients from asymptomatic carriers. In addition, chemokine profiles in asymptomatic carriers and HAM/TSP groups were similar, with no significant increased frequency of higher producers of chemokines in HAM/TSP individuals. Results indicate that the heterogeneity of the individuals in the groups regarding time of infection, duration of disease, proviral load level and other possible confound factors may impair the use of chemokines levels to monitor HTLV 1 carriers in clinical practice. J. Med. Virol. 88:1438-1447, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26800846 TI - Degradation and transformation of 17alpha-trenbolone in aerobic water-sediment systems. AB - Synovex(r) ONE is an extended-release implant containing the active ingredients estradiol benzoate and trenbolone acetate for use in beef steers and heifers. Trenbolone acetate is rapidly hydrolyzed in cattle to form 17beta-trenbolone and its isomer, 17alpha-trenbolone, which are further transformed to a secondary metabolite, trendione. As part of the environmental assessment for the use of Synovex ONE, data were generated to characterize the fate of 17alpha-trenbolone, which is the principal metabolite found in cattle excreta, in the environment. A study was conducted to determine the degradation and transformation of [14 C] 17alpha-trenbolone in 2 representative water-sediment systems under aerobic conditions. The same transformation products, 17beta-trenbolone and trendione, were formed, principally in the sediment phase, in both systems. From the production of these transformation products, the 50% disappearance time (DT50) values of 17beta-trenbolone and trendione were determined, along with the DT50 values of the parent compound and the total drug (17alpha-trenbolone + 17beta trenbolone + trendione). The DT50 values for the total system (aqueous and sediment phase) and for the total residues (17alpha-trenbolone + 17beta trenbolone + trendione) in the 2 systems were 34.7 d and 53.3 d, respectively. Environ Toxicol Chem 2017;36:630-635. (c) 2016 SETAC. PMID- 26800847 TI - SOT1, a pentatricopeptide repeat protein with a small MutS-related domain, is required for correct processing of plastid 23S-4.5S rRNA precursors in Arabidopsis thaliana. AB - Ribosomal RNA processing is essential for plastid ribosome biogenesis, but is still poorly understood in higher plants. Here, we show that SUPPRESSOR OF THYLAKOID FORMATION1 (SOT1), a plastid-localized pentatricopeptide repeat (PPR) protein with a small MutS-related domain, is required for maturation of the 23S 4.5S rRNA dicistron. Loss of SOT1 function leads to slower chloroplast development, suppression of leaf variegation, and abnormal 23S and 4.5S processing. Predictions based on the PPR motif sequences identified the 5' end of the 23S-4.5S rRNA dicistronic precursor as a putative SOT1 binding site. This was confirmed by electrophoretic mobility shift assay, and by loss of the abundant small RNA 'footprint' associated with this site in sot1 mutants. We found that more than half of the 23S-4.5S rRNA dicistrons in sot1 mutants contain eroded and/or unprocessed 5' and 3' ends, and that the endonucleolytic cleavage product normally released from the 5' end of the precursor is absent in a sot1 null mutant. We postulate that SOT1 binding protects the 5' extremity of the 23S-4.5S rRNA dicistron from exonucleolytic attack, and favours formation of the RNA structure that allows endonucleolytic processing of its 5' and 3' ends. PMID- 26800849 TI - Cross-Linked Hydrogels Formed through Diels-Alder Coupling of Furan- and Maleimide-Modified Poly(methyl vinyl ether-alt-maleic acid). AB - The Diels-Alder [4 + 2] cycloaddition between furan- and maleimide-functional polyanions was used to form cross-linked synthetic polymer hydrogels. Poly(methyl vinyl ether-alt-maleic anhydride) was reacted with furfurylamine or N-(2 aminoethyl)maleimide in acetonitrile to form pairs of furan- and maleimide functionalized poly(methyl vinyl ether-alt-maleic acid)s. Mixtures of these mutually reactive polyanions in water gelled within 15 min to 18 h, depending on degree of functionalization and polymer concentrations. Solution and magic-angle spinning (1)H NMR were used to confirm the formation of the Diels-Alder adduct, to analyze competing hydrolytic side reactions, and demonstrate postgelation functionalization. The effect of the degree of furan and maleimide functionalization, polymer concentration, pH, and calcium ion concentration, on gelation time, gel mechanical properties, and equilibrium swelling, are described. Release of dextran as a model drug was studied using fluorescence spectroscopy, as a function of gel composition and calcium treatment. PMID- 26800848 TI - Noninvasive measurement of renal oxygen extraction fraction under the influence of respiratory challenge. AB - PURPOSE: To demonstrate the feasibility of using a susceptibility-based magnetic resonance imaging (MRI) technique for measuring renal oxygen extraction fraction (OEF) changes under the influence of carbogen (97% O2 , 3% CO2 ) breathing. MATERIALS AND METHODS: Eight New Zealand White rabbits were included in this study with local animal care committee approval. For OEF measurement, an asymmetric spin echo (ASE) sequence was used to acquire source images and a susceptibility model was utilized for OEF estimation at 3.0T. Within-session and between-day tests were conducted to evaluate the reproducibility of this OEF measurement. OEF changes were measured under respiratory challenge with alternated air and carbogen (97% O2 , 3% CO2 ) breathing. For comparison, blood samples were collected for the measurement of pO2 . RESULTS: The within-session coefficients of variation (CVs) of renal OEF measurements were 6.62% in cortex and 5.92% in medulla, while between-day CVs were 7.52% in cortex and 8.03% in medulla. Under carbogen breathing, renal OEFs decreased significantly from 0.32 +/- 0.03 to 0.28 +/- 0.02 (P < 0.01) in cortex, and from 0.34 +/- 0.04 to 0.31 +/ 0.03 (P < 0.01) in medulla. No statistical difference of relative OEF change was seen between cortex and medulla (P = 0.93). In addition, negative correlation between renal OEF and blood pO2 was found (r = 0.68 (P < 0.05) in cortex, and r = 0.64 (P < 0.05) in medulla). CONCLUSION: This study demonstrates the feasibility of using a susceptibility-based OEF measurement method for the evaluation of renal oxygenation changes induced by carbogen breathing. J. Magn. Reson. Imaging 2016;44:230-237. PMID- 26800850 TI - Prediction of functionally significant single nucleotide polymorphisms in PTEN tumor suppressor gene: An in silico approach. AB - The phosphatase and tensin homolog (PTEN) gene plays a crucial role in signal transduction by negatively regulating the PI3K signaling pathway. It is the most frequent mutated gene in many human-related cancers. Considering its critical role, a functional analysis of missense mutations of PTEN gene was undertaken in this study. Thirty five nonsynonymous single nucleotide polymorphisms (nsSNPs) within the coding region of the PTEN gene were selected for our in silico investigation, and five nsSNPs (G129E, C124R, D252G, H61D, and R130G) were found to be deleterious based on combinatorial predictions of different computational tools. Moreover, molecular dynamics (MD) simulation was performed to investigate the conformational variation between native and all the five mutant PTEN proteins having predicted deleterious nsSNPs. The results of MD simulation of all mutant models illustrated variation in structural attributes such as root-mean-square deviation, root-mean-square fluctuation, radius of gyration, and total energy; which depicts the structural stability of PTEN protein. Furthermore, mutant PTEN protein structures also showed a significant variation in the solvent accessible surface area and hydrogen bond frequencies from the native PTEN structure. In conclusion, results of this study have established the deleterious effect of the all the five predicted nsSNPs on the PTEN protein structure. Thus, results of the current study can pave a new platform to sort out nsSNPs that can be undertaken for the confirmation of their phenotype and their correlation with diseased status in case of control studies. PMID- 26800851 TI - Changes in psychological well-being among heroin-dependent adolescents during psychologically supported opiate substitution treatment. AB - AIM: Heroin-dependent adolescents demonstrate high rates of comorbid psychological problems. Among heroin-dependent adults, opiate substitution treatment (OST) programmes appear to reduce mental health problems. We sought to examine the impact of OST on psychological well-being in adolescents, as this is unknown. METHODS: We conducted a prospective study examining psychological well being in heroin dependent adolescents, aged 18 years or younger, engaged in outpatient psychologically supported OST. Patients were treated with either methadone or buprenorphine. This was complimented with individual key working, counselling (motivational interviewing and cognitive behavioral therapy) and group work focusing on life skills. The Beck Youth Inventory was used to measure psychological well-being at treatment entry and repeated after 4 months of treatment. RESULTS: Among 55 consecutive treatment episodes, we examined the 32 episodes where the patient persisted with the OST programme. Polysubstance use was the norm at treatment entry. At follow-up, the median doses of methadone and buprenorphine were 50 mgs and 8 mgs, respectively. Only three patients were treated with antidepressant medication. There was significant improvement in the mean depression (65.0 to 57.9, P = 0.001), anxiety (61.7 to 57.0, P = 0.006) and anger (57.8 to 54.6, P = 0.009) subscale scores. The self-concept and disruptive behaviour subscale scores did not improve significantly. CONCLUSION: In this relatively short-term follow-up, psychosocially assisted OST appears to be associated with improved psychological well-being in heroin-dependent adolescents, especially in the area of depressive and anxiety symptoms. PMID- 26800852 TI - Heart acceleration and deceleration capacities associated with dilated cardiomyopathy. AB - BACKGROUND: Heart rate deceleration capacity and acceleration capacity are novel autonomic nervous system indicators of cardiac neural regulation. Dilated cardiomyopathy (DCM) changes cardiac electrophysiology; however, how deceleration capacity and acceleration capacity associated with DCM remain unclear. MATERIALS AND METHODS: To evaluate the association between heart rate acceleration capacity, deceleration capacity and DCM, 66 DCM patients with DCM and 209 controls were enrolled in the study. Demographic data, echocardiographic data, heart rate variability, deceleration capacity and acceleration capacity were collected. The association pattern between DCM and these indexes were studied by multiple logistic regression analysis. RESULTS: Deceleration capacity and acceleration capacity were independent risk factors for DCM with an odds ratio (OR) and 95% confidence interval (CI), determined by multiple logistic regression analysis, of 7.97 (3.87-16.42) and 0.09 (0.05-0.19), respectively. Univariate ordinal logistic regression analysis showed that acceleration capacity, fastest heart rate, standard deviation of normal-to-normal RR intervals (SDNN) and left ventricular ejection fraction (LEVF) associated with heart failure grade. The OR for each covariate was further adjusted for the effects of other significant covariates in multivariate ordinal logistic regression analysis. Acceleration capacity, fastest heart rate and LVEF were still independent risk factors in the final equation with ORs of 1.32 (1.03-1.79), 1.04 (0.01-1.07) and 0.46 (0.23 0.93), respectively. CONCLUSION: Heart rate acceleration capacity and deceleration capacity are independent risk factors for DCM, and acceleration capacity is a predictive factor for heart failure exacerbation in patients with DCM. PMID- 26800853 TI - Decreased peroxisome proliferator-activated receptor gamma level and signalling in sebaceous glands of patients with acne vulgaris. AB - Little is known about the altered lipid metabolism-related transcriptional events occuring in sebaceous glands of patients with acne vulgaris. Peroxisome proliferator-activated receptor (PPAR)gamma, a lipid-activated transcription factor, is implicated in differentiation and lipid metabolism of sebocytes. We have observed that PPARgamma and its target genes, ADRP (adipose differentiation related protein) and PGAR (PPARgamma angioprotein related protein) are expressed at lower levels in sebocytes from patients with acne than in those from healthy controls (HCs) Furthermore, endogenous PPARgamma activator lipids such as arachidonic acid-derived keto-metabolites (e.g. 5KETE, 12KETE) are increased in acne-involved and nonacne-involved skin of patients with acne, compared with skin from healthy individuals. Our findings highlight the possible anti-inflammatory role of endogenous ligand-activated PPARgamma signaling in human sebocyte biology, and suggest that modulating PPARgamma- expression and thereby signaling might be a promising strategy for the clinical management of acne vulgaris. PMID- 26800854 TI - Results of coil closure of patent ductus arteriosus using a tapered tip catheter for enhanced control. AB - OBJECTIVES: This article describes the efficacy and embolization rates of coil delivery via modified vertebral catheter (MVC) for patent ductus arteriosus (PDA) closure. BACKGROUND: Various techniques have been devised to enhance coil control and prevent embolization during PDA closure. Since 1995, they have delivered coils via tapered vertebral catheters for improved coil control. METHODS: Catheterization reports, angiograms, and echocardiograms were reviewed for patients with PDA occlusion via MVC from 2001 to 2014. Residual shunting was determined by angiography and echocardiogram within 24 hr post-procedure. Procedural success was defined as <= trivial angiographic and echocardiographic shunt, and no aortic nor LPA obstruction, after final coil delivery. RESULTS: About 125 coil occlusions were attempted in 103 patients. Minimal PDA diameter was 2 (0.6-6) mm. Four coils were removed with a snare/bioptome due to aortic/LPA obstruction following release. Seven were malpositioned while still held by the MVC of which three embolized while attempting withdrawal. Five embolized after full release from the MVC. The embolization rate was 6.4%. Embolizations were more likely in PDAs >= 2.5 mm (P < 0.05). Ultimately, 98/103 PDAs were occluded using the MVC. No patient had greater trivial residual shunt or aortic/LPA obstruction for an overall success rate of 95%. For PDAs < 2.5 mm the success rate was 97%. CONCLUSIONS: Coil delivery via MVC was safe and effective for small PDAs. While fully controlled release and retrieval devices are now available for PDA closure with lower embolization rates, coil occlusion by MVC should still be considered for small PDAs, especially in resource limited regions. (c) 2016 Wiley Periodicals, Inc. PMID- 26800855 TI - Haplotype hitchhiking promotes trait coselection in Brassica napus. AB - Local haplotype patterns surrounding densely spaced DNA markers with significant trait associations can reveal information on selective sweeps and genome diversity associated with important crop traits. Relationships between haplotype and phenotype diversity, coupled with analysis of gene content in conserved haplotype blocks, can provide insight into coselection for nonrelated traits. We performed genome-wide analysis of haplotypes associated with the important physiological and agronomic traits leaf chlorophyll and seed glucosinolate content, respectively, in the major oilseed crop species Brassica napus. A locus on chromosome A01 showed opposite effects on leaf chlorophyll content and seed glucosinolate content, attributed to strong linkage disequilibrium (LD) between orthologues of the chlorophyll biosynthesis genes EARLY LIGHT-INDUCED PROTEIN and CHLOROPHYLL SYNTHASE, and the glucosinolate synthesis gene ATP SULFURYLASE 1. Another conserved haplotype block, on chromosome A02, contained a number of chlorophyll-related genes in LD with orthologues of the key glucosinolate biosynthesis genes METHYLTHIOALKYMALATE SYNTHASE-LIKE 1 and 3. Multigene haplogroups were found to have a significantly greater contribution to variation for chlorophyll content than haplotypes for any single gene, suggesting positive effects of additive locus accumulation. Detailed reanalysis of population substructure revealed a clade of ten related accessions exhibiting high leaf chlorophyll and low seed glucosinolate content. These accessions each carried one of the above-mentioned haplotypes from A01 or A02, generally in combination with further chlorophyll-associated haplotypes from chromosomes A05 and/or C05. The phenotypic rather than pleiotropic correlations between leaf chlorophyll content index and seed GSL suggest that LD may have led to inadvertent coselection for these two traits. PMID- 26800856 TI - Inhibition of the contralesional dorsal premotor cortex improves motor function of the affected hand following stroke. AB - BACKGROUND AND PURPOSE: Numerous studies have shown that repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) may improve motor function of the affected hand after stroke. The effects of 1 Hz rTMS applied over the contralesional dorsal premotor cortex (PMd) on hand function and cortical neurophysiology in subacute stroke were examined. METHODS: Ten subacute stroke patients with mild hand motor impairment were enrolled in a prospective, double blind, randomized, placebo-controlled, crossover study with two intervention sessions. 1 Hz rTMS was applied over the contralesional PMd (real rTMS, 900 pulses at 110% of the motor threshold; sham rTMS, 900 pulses at 0% of the motor threshold). Tests of hand function (Jebsen-Taylor hand function test, box and block test) and neurophysiological evaluations (resting motor threshold, motor evoked potentials, cortical silent period, ipsilateral silent period) were obtained from both hands and hemispheres prior to (baseline) and after each treatment. RESULTS: Hand function tests revealed significant improvement of motor function of the affected but not of the unaffected hand after real rTMS only. Neither intervention changed the neurophysiological measures in comparison to baseline. CONCLUSION: One hertz rTMS over the contralesional PMd improves motor function of the affected hand in subacute stroke. The PMd may be a novel rTMS target to treat motor impairment after stroke. PMID- 26800857 TI - An estimation of the incidence of tuberous sclerosis complex in a nationwide retrospective cohort study (1997-2010). AB - BACKGROUND: Tuberous sclerosis complex (TSC) is caused by mutations in TSC1 and TSC2, leading to mammalian target of rapamycin hyperactivation. Patients with TSC develop hamartomas in brain, lungs, liver and skin. Two epidemiological studies, performed in Minnesota, U.S.A., have estimated the incidence of TSC to be 0.28 0.56 per 100 000 person-years (PY), based on < 12 patients. Furthermore, whether common comorbidities are associated with this rare disease is not known. OBJECTIVES: To estimate the incidence of TSC and investigate the associations of TSC with other comorbidities, including diabetes, peptic ulcers, stroke and myocardial infarction. METHODS: We estimated the incidence and prevalence of TSC and its comorbidities from 1997 to 2010, based on the Catastrophic Illness Certificate disease database and a beneficiary cohort of 1 million people. RESULTS: The incidence of TSC in Taiwan is 0.153 per 100 000 PY. The number of patients identified with TSC in Taiwan doubled from 206 in 2006 to 471 in 2010. In 2010, the prevalence of TSC in Taiwan was estimated to be 1.58 in 100 000. We confirmed that female patients with TSC are more likely to develop renal tumours than male patients. Surprisingly, patients with TSC have a significantly decreased risk of developing peptic ulcers compared with controls. CONCLUSIONS: This is the first large-scale and longitudinal incidence study of TSC. This study provides compelling evidence that TSC mutations in humans are associated with a decreased risk of peptic ulcers. PMID- 26800858 TI - Altered short-term plasticity within the working memory neural network: Is it neuroticism or is it depression? AB - In the present article, we discuss (1) the importance of assessing and statistically considering both clinical and subclinical forms of depression when examining the relationship between neuroticism and short-term plasticity within the working memory neural network, and (2) the hypothesis of an antagonism between neuroticism and conscientiousness in personality research. We suggest that (1) neuroticism and depression should be examined in a relational manner, and (2) neuroticism and conscientiousness should not be antagonized. PMID- 26800859 TI - Self-report of gingival problems and periodontitis in indigenous and non indigenous populations in Chiapas, Mexico. AB - OBJECTIVE: To estimate the prevalence of self-reported gingival and periodontal conditions and their association with smoking, oral hygiene, indigenous origin, diabetes and location (urban or rural) in indigenous and non-indigenous adults in Chiapas, Mexico. METHODS: A cross-sectional study of 1,749 persons, >=20 years of age, living in four rural and four urban marginal localities in Comitan (Chiapas, Mexico). The variables investigated were: age; sex; indigenous origin; oral hygiene; halitosis; chewing ability; gingival conditions; periodontitis; smoking; alcoholism; diabetes; and location. Bivariate analysis and a logistic regression model were used to identify the association of periodontitis with the independent variables. RESULTS: In total, 762 (43.6%) indigenous and 987 (56.4%) non indigenous persons were interviewed. Their mean age was 41 +/- 14 years, 66.7% were women and 43.8% lived in rural locations. Gingival problems were reported by 68.5% and periodontitis by 8.7%. In total, 17.9% had used dental services during the previous year, 28.7% wore a removable partial or a complete dental prosthesis, 63.7% had lost at least one tooth, the prevalence of diabetes was 9.2% and the prevalence of smoking was 12.2%. The logistic regression model showed that age, diabetes and the interaction between rural location and indigenous origin were associated with the presence of periodontitis. CONCLUSIONS: Indigenous people living in rural areas are more likely to have periodontitis. It is necessary to promote oral health practices in indigenous and marginalised populations with a focus on community-oriented primary care. PMID- 26800860 TI - Expression of a constitutively active nitrate reductase variant in tobacco reduces tobacco-specific nitrosamine accumulation in cured leaves and cigarette smoke. AB - Burley tobaccos (Nicotiana tabacum) display a nitrogen-use-deficiency phenotype that is associated with the accumulation of high levels of nitrate within the leaf, a trait correlated with production of a class of compounds referred to as tobacco-specific nitrosamines (TSNAs). Two TSNA species, 4-(methylnitrosamino)-1 (3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN), have been shown to be strong carcinogens in numerous animal studies. We investigated the potential of molecular genetic strategies to lower nitrate levels in burley tobaccos by overexpressing genes encoding key enzymes of the nitrogen-assimilation pathway. Of the various constructs tested, only the expression of a constitutively active nitrate reductase (NR) dramatically decreased free nitrate levels in the leaves. Field-grown tobacco plants expressing this NR variant exhibited greatly reduced levels of TSNAs in both cured leaves and mainstream smoke of cigarettes made from these materials. Decreasing leaf nitrate levels via expression of a constitutively active NR enzyme represents an exceptionally promising means for reducing the production of NNN and NNK, two of the most well-documented animal carcinogens found in tobacco products. PMID- 26800861 TI - EchinoDB, an application for comparative transcriptomics of deeply-sampled clades of echinoderms. AB - BACKGROUND: One of our goals for the echinoderm tree of life project (http://echinotol.org) is to identify orthologs suitable for phylogenetic analysis from next-generation transcriptome data. The current dataset is the largest assembled for echinoderm phylogeny and transcriptomics. We used RNA-Seq to profile adult tissues from 42 echinoderm specimens from 24 orders and 37 families. In order to achieve sampling members of clades that span key evolutionary divergence, many of our exemplars were collected from deep and polar seas. DESCRIPTION: A small fraction of the transcriptome data we produced is being used for phylogenetic reconstruction. Thus to make a larger dataset available to researchers with a wide variety of interests, we made a web-based application, EchinoDB (http://echinodb.uncc.edu). EchinoDB is a repository of orthologous transcripts from echinoderms that is searchable via keywords and sequence similarity. CONCLUSIONS: From transcripts we identified 749,397 clusters of orthologous loci. We have developed the information technology to manage and search the loci their annotations with respect to the Sea Urchin (Strongylocentrotus purpuratus) genome. Several users have already taken advantage of these data for spin-off projects in developmental biology, gene family studies, and neuroscience. We hope others will search EchinoDB to discover datasets relevant to a variety of additional questions in comparative biology. PMID- 26800862 TI - Management of rhinosinusitis during pregnancy: systematic review and expert panel recommendations. AB - BACKGROUND: Management of rhinosinusitis during pregnancy requires special considerations. OBJECTIVES: 1. Conduct a systematic literature review for acute and chronic rhinosinusitis (CRS) management during pregnancy. 2. Make evidence based recommendations. METHODS: The systematic review was conducted using MEDLINE and EMBASE databases and relevant search terms. Title, abstract and full manuscript review were conducted by two authors independently. A multispecialty panel with expertise in management of Rhinological disorders, Allergy-Immunology, and Obstetrics-Gynecology was invited to review the systematic review. Recommendations were sought on use of following for CRS management during pregnancy: oral corticosteroids; antibiotics; leukotrienes; topical corticosteroid spray/irrigations/drops; aspirin desensitization; elective surgery for CRS with polyps prior to planned pregnancy; vaginal birth versus planned Caesarian for skull base erosions/ prior CSF rhinorrhea. RESULTS: Eighty-eight manuscripts underwent full review after screening 3052 abstracts. No relevant level 1, 2, or 3 studies were found. Expert panel recommendations for rhinosinusitis management during pregnancy included continuing nasal corticosteroid sprays for CRS maintenance, using pregnancy-safe antibiotics for acute rhinosinusitis and CRS exacerbations, and discontinuing aspirin desensitization for aspirin exacerbated respiratory disease. The manuscript presents detailed recommendations. CONCLUSIONS: The lack of evidence pertinent to managing rhinosinusitis during pregnancy warrants future trials. Expert recommendations constitute the current best available evidence. PMID- 26800863 TI - A phagocytosis assay for oxidized low-density lipoprotein versus immunoglobulin G coated microbeads in human U937 macrophages. AB - The human monocyte cell line U937 was differentiated into an adherent macrophage phenotype using phorbol 12-myristate 13-acetate (PMA) to assay the phagocytosis of oxidized low-density lipoprotein (oxLDL) that may play a role in atherosclerosis. Microbeads were coated with the inflammatory ligand oxLDL to create a novel phagocytosis assay that models the binding of macrophages to oxLDL in the solid phase such as found in the fatty streaks of the arteries. The oxLDL was prepared with LDL from human ethylenediaminetetraacetic acid (EDTA) plasma oxidized with an excess (5 mM) of the strong oxidizing agent CuSO4 and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with Western blot. The binding of the oxLDL to the beads was confirmed by DilC18-oxLDL staining and confocal microscopy in addition to trypsin digestion of the microbeads for liquid chromatography, electrospray ionization, and tandem mass spectrometry. Phagocytosis of the oxLDL versus human bulk immunoglobulin G1 (IgG1)-coated microbeads was assayed over time, in the presence and absence of serum factors, by pulse chase and with enzyme inhibitor treatments. The ligand beads were then stained with specific antibodies to oxLDL versus human IgG to differentially stain external versus engulfed ligand microbeads. The phagocytosis of oxLDL and IgG ligand microbeads was abolished by the actin polymerization inhibitors cytochalasin D and latrunculin. Pharmacological inhibitors of the receptor enzymes JAK, SRC, and PLC prevented both IgG and oxLDL receptor function. In contrast, the function of the oxLDL phagocytic receptor complex was more sensitive to inhibition of PTK2, PKC, and SYK activity. PMID- 26800864 TI - Quantification of biofilm exopolysaccharides using an in situ assay with periodic acid-Schiff reagent. AB - A novel approach to the quantification of extracellular polysaccharides in miniaturized biofilms presenting a wide variety of extracellular matrices was developed. The assay used the periodic acid-Schiff reagent and was first calibrated on dextran and alginate solutions. Then it was implemented on 24-h and 48-h biofilms from three strains known to produce different exopolymeric substances (Pseudomonas aeruginosa, Bacillus licheniformis, Weissella confusa). The assay allowed quantification of the total exopolysaccharides, taking into account possible interferences due to cells or other main expolymers of the matrix (eDNA, proteins). PMID- 26800865 TI - The impact of tree-stand falls on a Level 1 trauma center in West Michigan. AB - BACKGROUND: Falls from tree stands are common during the hunting season. We examined the impact of this injury mechanism on a Level 1 trauma center in West Michigan. METHODS: Retrospective cohort study examining tree-stand fall patients between 2001 and 2013. RESULTS: A total of 193 patients were included. Less than 3% of patients were wearing a harness. Falls from greater than 20 feet were associated with a higher injury severity score (P = .018). The injury severity score and Glasgow coma scale of the normal weight and overweight (OW) groups were the same. Overall 91.3% of normal weight patients were discharged home vs 63.5% of OW patients (P = .009). Median rehab stay was 12 days (3 to 92), and median charge was $24,048 (2,398 to 134,752). CONCLUSIONS: Tree-stand falls cause significant injury, especially from heights greater than 20 feet. OW patients more frequently require rehabilitation. The infrequent use of safety harnesses is alarming. PMID- 26800866 TI - Use of a simplified frailty index to predict Clavien 4 complications and mortality after hepatectomy: analysis of the National Surgical Quality Improvement Project database. AB - BACKGROUND: An aging surgical population places an increasing burden on surgeons to accurately risk stratify and counsel patients. Preoperative frailty assessments are a promising new modality to better evaluate patients but can often be time consuming. Data regarding frailty and hepatectomy outcomes have not been published to date. METHOD: Using the National Surgical Quality Improvement Project database, we examined hepatectomy patients 2005 to 11 and correlated frailty scores with outcomes of major morbidity, mortality, and extended length of stay, using a previously validated modified frailty index score. Frailty was compared against age, American Society of Anesthesiologists class, and other common risk variables. RESULTS: Multivariate regression identified frailty as the strongest predictor of Clavien 4 complications (OR = 40.0, 95% CI = 15.2 to 105.0), and mortality (OR = 26.4, 95% CI = 7.7 to 88.2). As the frailty score increased, there was a statistically significant increase in Clavien 4 complications, mortality, and extended length of stay (P < .001 for all). CONCLUSIONS: Frailty is a significant factor in morbidity and mortality after hepatectomy. Use of the modified frailty index allows for feasibility of data collection in a busy clinical setting. PMID- 26800867 TI - Necrotizing enterocolitis and the use of loop diuretics in very low birth weight neonates. AB - BACKGROUND: Necrotizing enterocolitis (NEC) is a gastrointestinal disease of premature, very low birth weight neonates resulting in sepsis and death. Loop diuretics are widely used in neonates as a treatment for pulmonary fluid retention. An association between diuretic use and NEC has not been explored. METHODS: The medical records of all neonates admitted to Duke Children's Hospital between 2007 and 2012 with a birth weight <=1,500 grams were reviewed. RESULTS: Using multivariable logistic regression analysis, we found that loop diuretic administration was not a risk factor for the development of NEC. On subanalysis, 75% of medical NEC infants had prior exposure to loop diuretics, compared with 100% of surgical NEC infants (P = .004). CONCLUSIONS: Loop diuretics do not increase the risk of development of NEC in very low birth weight neonates. However, on diagnosis of NEC, administration of loop diuretics may be associated with the progression of NEC severity from medical NEC to surgical NEC. PMID- 26800868 TI - 2015 William Hunter Harridge lecture: how did we go from operating on nearly all injured kidneys to operating on almost none of them? AB - The 2015 William H. Harridge lecture of the 2015 Midwest Surgical Association concentrated on the evolution and performance characteristics of nonoperative management of even severe renal injury. One of the first mentions of nonoperative renal trauma occurs after World War II. Since that time through the early 2000s, only 1 or fewer papers per year appeared in the literature. The mid-2000s had an explosion of interest and publications on the subject, resulting in our modern understanding of the principles. The principles of nonoperative management are as follows: (1) operate immediately if the patient is bleeding to death; (2) observe initially, but step in with metered responses as necessary; (3) use ureteral stents for symptomatic or growing urinoma; (4) use angioembolization for nonemergent bleeding or for urgent bleeding if your center can manage this; and (5) do open surgery when needed (not "never"). PMID- 26800869 TI - Proresolving Actions of Synthetic and Natural Protease Inhibitors Are Mediated by Annexin A1. AB - Annexin A1 (AnxA1) is a glucocorticoid-regulated protein endowed with anti inflammatory and proresolving properties. Intact AnxA1 is a 37-kDa protein that may be cleaved in vivo at the N-terminal region by neutrophil proteases including elastase and proteinase-3, generating the 33-kDa isoform that is largely inactive. In this study, we investigated the dynamics of AnxA1 expression and the effects of synthetic (sivelestat [SIV]; Eglin) and natural (secretory leukocyte protease inhibitor [SLPI]; Elafin) protease inhibitors on the resolution of LPS induced inflammation. During the settings of LPS inflammation AnxA1 cleavage associated closely with the peak of neutrophil and elastase expression and activity. SLPI expression increased during resolving phase of the pleurisy. Therapeutic treatment of LPS-challenge mice with recombinant human SLPI or Elafin accelerated resolution, an effect associated with increased numbers of apoptotic neutrophils in the pleural exudates, inhibition of elastase, and modulation of the survival-controlling proteins NF-kappaB and Mcl-1. Similar effects were observed with SIV, which dose-dependently inhibited neutrophil elastase and shortened resolution intervals. Mechanistically, SIV-induced resolution was caspase-dependent, associated to increased levels of intact AnxA1 and decreased expression of NF-kappaB and Mcl-1. The proresolving effect of antiproteases was also observed in a model of monosodium urate crystals-induced inflammation. SIV skewed macrophages toward resolving phenotypes and enhanced efferocytosis of apoptotic neutrophils. A neutralizing antiserum against AnxA1 and a nonselective antagonist of AnxA1 receptor abolished the accelerated resolution promoted by SIV. Collectively, these results show that elastase inhibition not only inhibits inflammation but actually promotes resolution, and this response is mediated by protection of endogenous intact AnxA1 with ensuing augmentation of neutrophil apoptosis. PMID- 26800870 TI - Critical Role of Antimicrobial Peptide Cathelicidin for Controlling Helicobacter pylori Survival and Infection. AB - The antimicrobial peptide cathelicidin is critical for protection against different kinds of microbial infection. This study sought to elucidate the protective action of cathelicidin against Helicobacter pylori infection and its associated gastritis. Exogenous cathelicidin was found to inhibit H. pylori growth, destroy the bacteria biofilm, and induce morphological alterations in H. pylori membrane. Additionally, knockdown of endogenous cathelicidin in human gastric epithelial HFE-145 cells markedly increased the intracellular survival of H. pylori. Consistently, cathelicidin knockout mice exhibited stronger H. pylori colonization, higher expression of proinflammatory cytokines IL-6, IL-1beta, and ICAM1, and lower expression of the anti-inflammatory cytokine IL-10 in the gastric mucosa upon H. pylori infection. In wild-type mice, H. pylori infection also stimulated gastric epithelium-derived cathelicidin production. Importantly, pretreatment with bioengineered Lactococcus lactis that actively secretes cathelicidin significantly increased mucosal cathelicidin levels and reduced H. pylori infection and the associated inflammation. Moreover, cathelicidin strengthened the barrier function of gastric mucosa by stimulating mucus synthesis. Collectively, these findings indicate that cathelicidin plays a significant role as a potential natural antibiotic for H. pylori clearance and a therapeutic agent for chronic gastritis. PMID- 26800871 TI - The MHC Class I Cancer-Associated Neoepitope Trh4 Linked with Impaired Peptide Processing Induces a Unique Noncanonical TCR Conformer. AB - MHC class I downregulation represents a significant challenge for successful T cell-based immunotherapy. T cell epitopes associated with impaired peptide processing (TEIPP) constitute a novel category of immunogenic Ags that are selectively presented on transporter associated with Ag processing-deficient cells. The TEIPP neoepitopes are CD8 T cell targets, derived from nonmutated self proteins that might be exploited to prevent immune escape. In this study, the crystal structure of H-2D(b) in complex with the first identified TEIPP Ag (MCLRMTAVM) derived from the Trh4 protein has been determined to 2.25 A resolution. In contrast to prototypic H-2D(b) peptides, Trh4 takes a noncanonical peptide-binding pattern with extensive sulfur-pi interactions that contribute to the overall complex stability. Importantly, the noncanonical methionine at peptide position 5 acts as a main anchor, altering only the conformation of the H 2D(b) residues Y156 and H155 and thereby forming a unique MHC/peptide conformer that is essential for recognition by TEIPP-specific T cells. Substitution of peptide residues p2C and p5M to the conservative alpha-aminobutyric acid and norleucine, respectively, significantly reduced complex stability, without altering peptide conformation or T cell recognition. In contrast, substitution of p5M to a conventional asparagine abolished recognition by the H-2D(b)/Trh4 specific T cell clone LnB5. We anticipate that the H-2D(b)/Trh4 complex represents the first example, to our knowledge, of a broader repertoire of alternative MHC class I binders. PMID- 26800873 TI - Degranulating Neutrophils Promote Leukotriene B4 Production by Infected Macrophages To Kill Leishmania amazonensis Parasites. AB - Neutrophils mediate early responses against pathogens, and they become activated during endothelial transmigration toward the inflammatory site. In the current study, human neutrophils were activated in vitro with immobilized extracellular matrix proteins, such as fibronectin (FN), collagen, and laminin. Neutrophil activation by FN, but not other extracellular matrix proteins, induces the release of the granules' contents, measured as matrix metalloproteinase 9 and neutrophil elastase activity in culture supernatant, as well as reactive oxygen species production. Upon contact with Leishmania amazonensis-infected macrophages, these FN-activated neutrophils reduce the parasite burden through a mechanism independent of cell contact. The release of granule proteases, such as myeloperoxidase, neutrophil elastase, and matrix metalloproteinase 9, activates macrophages through TLRs, leading to the production of inflammatory mediators, TNF-alpha and leukotriene B4 (LTB4), which are involved in parasite killing by infected macrophages. The pharmacological inhibition of degranulation reverted this effect, abolishing LTB4 and TNF production. Together, these results suggest that FN-driven degranulation of neutrophils induces the production of LTB4 and TNF by infected macrophages, leading to the control of Leishmania infection. PMID- 26800872 TI - C1P Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Preventing NF kappaB Activation in Neutrophils. AB - Recently, ceramide-1-phosphate (C1P) has been shown to modulate acute inflammatory events. Acute lung injury (Arnalich et al. 2000. Infect. Immun. 68: 1942-1945) is characterized by rapid alveolar injury, lung inflammation, induced cytokine production, neutrophil accumulation, and vascular leakage leading to lung edema. The aim of this study was to investigate the role of C1P during LPS induced acute lung injury in mice. To evaluate the effect of C1P, we used a prophylactic and therapeutic LPS-induced ALI model in C57BL/6 male mice. Our studies revealed that intrapulmonary application of C1P before (prophylactic) or 24 h after (therapeutic) LPS instillation decreased neutrophil trafficking to the lung, proinflammatory cytokine levels in bronchoalveolar lavage, and alveolar capillary leakage. Mechanistically, C1P inhibited the LPS-triggered NF-kappaB levels in lung tissue in vivo. In addition, ex vivo experiments revealed that C1P also attenuates LPS-induced NF-kappaB phosphorylation and IL-8 production in human neutrophils. These results indicate C1P playing a role in dampening LPS induced acute lung inflammation and suggest that C1P could be a valuable candidate for treatment of ALI. PMID- 26800874 TI - Human Endothelial Cell Activation by Escherichia coli and Staphylococcus aureus Is Mediated by TNF and IL-1beta Secondarily to Activation of C5 and CD14 in Whole Blood. AB - Endothelial cells (EC) play a central role in inflammation. E-selectin and ICAM-1 expression are essential for leukocyte recruitment and are good markers of EC activation. Most studies of EC activation are done in vitro using isolated mediators. The aim of the present study was to examine the relative importance of pattern recognition systems and downstream mediators in bacteria-induced EC activation in a physiological relevant human model, using EC incubated with whole blood. HUVEC were incubated with human whole blood. Escherichia coli- and Staphylococcus aureus-induced EC activation was measured by E-selectin and ICAM-1 expression using flow cytometry. The mAb 18D11 was used to neutralize CD14, and the lipid A analog eritoran was used to block TLR4/MD2. C5 cleavage was inhibited using eculizumab, and C5aR1 was blocked by an antagonist. Infliximab and canakinumab were used to neutralize TNF and IL-1beta. The EC were minimally activated when bacteria were incubated in serum, whereas a substantial EC activation was seen when the bacteria were incubated in whole blood. E. coli induced activation was largely CD14-dependent, whereas S. aureus mainly caused a C5aR1-mediated response. Combined CD14 and C5 inhibition reduced E-selectin and ICAM-1 expression by 96 and 98% for E. coli and by 70 and 75% for S. aureus. Finally, the EC activation by both bacteria was completely abolished by combined inhibition of TNF and IL-1beta. E. coli and S. aureus activated EC in a CD14- and C5-dependent manner with subsequent leukocyte secretion of TNF and IL-1beta mediating the effect. PMID- 26800875 TI - Differential Effects of Escherichia coli Nissle and Lactobacillus rhamnosus Strain GG on Human Rotavirus Binding, Infection, and B Cell Immunity. AB - Rotavirus (RV) causes significant morbidity and mortality in children worldwide. The intestinal microbiota plays an important role in modulating host-pathogen interactions, but little is known about the impact of commonly used probiotics on human RV (HRV) infection. In this study, we compared the immunomodulatory effects of Gram-positive (Lactobacillus rhamnosus strain GG [LGG]) and Gram-negative (Escherichia coli Nissle [EcN]) probiotic bacteria on virulent human rotavirus (VirHRV) infection and immunity using neonatal gnotobiotic piglets. Gnotobiotic piglets were colonized with EcN, LGG, or EcN+LGG or uncolonized and challenged with VirHRV. Mean peak virus shedding titers and mean cumulative fecal scores were significantly lower in EcN-colonized compared with LGG-colonized or uncolonized piglets. Reduced viral shedding titers were correlated with significantly reduced small intestinal HRV IgA Ab responses in EcN-colonized compared with uncolonized piglets post-VirHRV challenge. However the total IgA levels post-VirHRV challenge in the intestine and pre-VirHRV challenge in serum were significantly higher in EcN-colonized than in LGG-colonized piglets. In vitro treatment of mononuclear cells with these probiotics demonstrated that EcN, but not LGG, induced IL-6, IL-10, and IgA, with the latter partially dependent on IL-10. However, addition of exogenous recombinant porcine IL-10 + IL-6 to mononuclear cells cocultured with LGG significantly enhanced IgA responses. The greater effectiveness of EcN in moderating HRV infection may also be explained by the binding of EcN but not LGG to Wa HRV particles or HRV 2/4/6 virus-like particles but not 2/6 virus-like particles. Results suggest that EcN and LGG differentially modulate RV infection and B cell responses. PMID- 26800876 TI - Hepatocyte Nuclear Factor 1A Is a Cell-Intrinsic Transcription Factor Required for B Cell Differentiation and Development in Mice. AB - The hepatocyte NF (HNF) family of transcription factors regulates the complex gene networks involved in lipid, carbohydrate, and protein metabolism. In humans, HNF1A mutations cause maturity onset of diabetes in the young type 3, whereas murine HNF6 participates in fetal liver B lymphopoiesis. In this study, we have identified a crucial role for the prototypical member of the family HNF1A in adult bone marrow B lymphopoiesis. HNF1A(-/-) mice exhibited a clear reduction in total blood and splenic B cells and a further pronounced one in transitional B cells. In HNF1A(-/-) bone marrow, all B cell progenitors-from pre-pro-/early pro B cells to immature B cells-were dramatically reduced and their proliferation rate suppressed. IL-7 administration in vivo failed to boost B cell development in HNF1A(-/-) mice, whereas IL-7 stimulation of HNF1A(-/-) B cell progenitors in vitro revealed a marked impairment in STAT5 phosphorylation. The B cell differentiation potential of HNF1A(-/-) common lymphoid progenitors was severely impaired in vitro, and the expression of the B lymphopoiesis-promoting transcription factors E2A, EBF1, Pax5, and Bach2 was reduced in B cell progenitors in vivo. HNF1A(-/-) bone marrow chimera featured a dramatic defect in B lymphopoiesis recapitulating that of global HNF1A deficiency. The HNF1A(-/-) lymphopoiesis defect was confined to B cells as T lymphopoiesis was unaffected, and bone marrow common lymphoid progenitors and hematopoietic stem cells were even increased. Our data demonstrate that HNF1A is an important cell-intrinsic transcription factor in adult B lymphopoiesis and suggest the IL-7R/STAT5 module to be causally involved in mediating its function. PMID- 26800877 TI - Risk factors for incident HIV infection among antenatal mothers in rural Eastern Cape, South Africa. AB - BACKGROUND: The prevalence of HIV among antenatal clients in South Africa has remained at a very high rate of about 29% despite substantial decline in several sub-Saharan countries. There is a paucity of data on risk factors for incident HIV infection among antenatal mothers and women within the reproductive age bracket in local settings in the Eastern Cape, South Africa. OBJECTIVE: To establish the risk factors for incident HIV infection among antenatal clients aged 18-49 years attending public antenatal clinics in rural Eastern Cape, South Africa. DESIGN: This was an unmatched case-control study carried out in public health antenatal clinics of King Sabata District Municipality between January and March 2014. The cases comprised 100 clients with recent HIV infection; the controls were 200 HIV-negative antenatal clients. Socio-demographic, sexual, and behavioral data were collected using interviewer-administered questionnaires adapted from the standard DHS5 women's questionnaire. Multivariate logistic regression models were used to identify the independent risk factors for HIV infection. A p<0.05 was considered statistically significant. RESULTS: The independent risk factors for incident HIV infection were economic dependence on the partner, having older male partners especially among women aged <=20 years, and sex under the influence of alcohol. CONCLUSIONS: Therefore, effective prevention of HIV among antenatal mothers in KSDM must target the improvement of the economic status of women, thereby reducing economic dependence on their sexual partners; address the prevalent phenomenon of cross-generation sex among women aged <20 years; and regulate the brewing, marketing, and consumption of alcohol. PMID- 26800878 TI - Mechanisms underlying epigenetic and transcriptional heterogeneity in Chinese hamster ovary (CHO) cell lines. AB - BACKGROUND: Recombinant cell lines developed for therapeutic antibody production often suffer instability or lose recombinant protein expression during long-term culture. Heterogeneous gene expression among cell line subclones may result from epigenetic modifications of DNA or histones, the protein component of chromatin. We thus investigated in such cell lines, DNA methylation and the chromatin environment along the human eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) promoter in an antibody protein-expression vector which was integrated into the Chinese hamster ovary (CHO) cell line genome. RESULTS: We analyzed four PT1-CHO cell lines which exhibited losses of protein expression at advanced passage number (>P35) growing in adherent conditions and in culture medium with 10 % FCS. These cell lines exhibited different integration sites and transgene copy numbers as determined by fluorescence in situ hybridization (FISH) and quantitative PCR (qPCR), respectively. By qRT-PCR, we analyzed the recombinant mRNA expression and correlated it with DNA methylation and with results from various approaches interrogating the chromatin landscape along the EEF1A1 promoter region. Each PT1-CHO cell line displayed specific epigenetic signatures or chromatin marks correlating with recombinant mRNA expression. The cell line with the lowest recombinant mRNA expression (PT1-1) was characterized by the highest nucleosome occupancy and displayed the lowest enrichment for histone marks associated with active transcription. In contrast, the cell line with the highest recombinant mRNA expression (PT1-55) exhibited the highest numbers of formaldehyde-assisted isolation of regulatory elements (FAIRE)-enriched regions, and was marked by enrichment for histone modifications H3K9ac and H3K9me3. Another cell line with the second highest recombinant mRNA transcription and the most stable protein expression (PT1-7) had the highest enrichments of the histone variants H3.3 and H2A.Z, and the histone modification H3K9ac. A further cell line (PT1-30) scored the highest enrichments for the bivalent marks H3K4me3 and H3K27me3. Finally, DNA methylation made a contribution, but only in the culture medium with reduced FCS or in a different expression vector. CONCLUSIONS: Our results suggest that the chromatin state along the EEF1A1 promoter region can help predict recombinant mRNA expression, and thus may assist in selecting desirable clones during cell line development for protein production. PMID- 26800879 TI - Sharing a resource with randomly arriving foragers. AB - We consider a problem of foraging where identical foragers, or predators, arrive as a stochastic Poisson process on the same patch of resource. We provide effective formulas for the expected resource intake of any of the agents, as a function of its rank, given their common functional response. We give a general theory, both in finite and infinite horizon, and show two examples of applications to harvesting a common under different assumptions about the resource dynamics and the functional response, and an example of application on a model that fits, among others, a problem of evolution of fungal plant parasites. PMID- 26800880 TI - RapidArc for centrally recurrent cervical cancer in the vaginal cuff following primary surgical therapy: a case report. AB - BACKGROUND: Pelvic recurrences of cervical cancer after primary surgical treatment can be potentially cured with radical hysterectomy or chemoradiation therapy. Combined radio-chemotherapy is believed to improve results compared to other option. Currently, RapidArc radiotherapy is considered an excellent technological advance that shows great potential for producing highly conformal doses to treatment volumes. CASE PRESENTATION: We present a case of a 67-year-old woman with history of early cervical cancer initially treated by radical laparoscopic hysterectomy. More than 5 years later, the patient presented with a central pelvic vaginal cuff recurrence that is histologically confirmed. Salvage radiotherapy using RapidArc with concurrent cisplatin-based chemotherapy was indicated. A high dose of 70 Gy was delivered to the gross recurrent disease with simultaneous integrated boost (SIB) to the subclinical disease and good sparing of organs at risk especially the rectum and sigmoid. CONCLUSIONS: This case clearly demonstrates a large benefit for salvage RapidArc radiotherapy to central pelvic recurrences of gynecological cancers with an excellent rate of local control and less rate of toxicity. PMID- 26800881 TI - Differential impacts of cardiac and abdominal ectopic fat deposits on cardiometabolic risk stratification. AB - BACKGROUND: Previous studies have shown that excessive abdominal visceral adipose tissue (AVAT) and epicardial adipose tissue (EAT) are risk factors of cardiometabolic disease; we hypothesized there is differential contribution of abdominal and cardiac fat deposits to the cardiometabolic profiles. METHODS: Two hundred eight consecutive subjects with clinical suspicion of coronary artery disease (CAD) who underwent cardiac and abdominal CT for Agatston score and abdominal visceral fat measurement were retrospectively analyzed. Regional thickness of EAT (EATth), total volume of EAT, total volume of paracardial adipose tissue (PAT) and total volume of AVAT from L2 to L5 level were measured. The relationships between abdominal and cardiac adipose tissue measurements, the number of components of metabolic syndrome, and the severity of Agatston score on a four ranking scale (0, 1-10,11-100, 101-400, >400) were investigated. RESULTS: The amounts of AVAT, EAT, PAT and EATth-LAVG showed a significant linear trend with increasing number (0-5) of components in metabolic syndrome (AVAT, EAT and PAT P for trend <0.0001; EATth-LVAG P for trend <0.001). EATth at left atrioventricular groove (EATth-LAVG) showed significant linear trend with the severity of Agatston score on a four ranking scale (P for trend <0.0001). In multivariate binary regression analysis, total volume of AVAT was the sole adiposity predictor for metabolic syndrome independent to age, gender, and waist circumference (odds ratio of 1.20, 95 % CI 1.08-1.32, p < 0.001) while total volume of EAT, PAT, and EATth-LAVG were not. In contrary, EATth-LAVG was the sole adiposity predictor for Agatston score >400 (odds ratio of 1.11, 95% CI 1.034 1.184, p = 0.004). CONCLUSIONS: Excessive total volume of AVAT appears to be preferentially associated with metabolic syndrome; while EAT, esp. EATth-LAVG is preferentially associated with coronary artery disease. This differential effect of the two adiposities deserves a large-scale cohort study for further investigation. PMID- 26800883 TI - Radiobiological impact of dose calculation algorithms on biologically optimized IMRT lung stereotactic body radiation therapy plans. AB - BACKGROUND: The aim of this study is to evaluate the radiobiological impact of Acuros XB (AXB) vs. Anisotropic Analytic Algorithm (AAA) dose calculation algorithms in combined dose-volume and biological optimized IMRT plans of SBRT treatments for non-small-cell lung cancer (NSCLC) patients. METHODS: Twenty eight patients with NSCLC previously treated SBRT were re-planned using Varian Eclipse (V11) with combined dose-volume and biological optimization IMRT sliding window technique. The total dose prescribed to the PTV was 60 Gy with 12 Gy per fraction. The plans were initially optimized using AAA algorithm, and then were recomputed using AXB using the same MUs and MLC files to compare with the dose distribution of the original plans and assess the radiobiological as well as dosimetric impact of the two different dose algorithms. The Poisson Linear Quadatric (PLQ) and Lyman-Kutcher-Burman (LKB) models were used for estimating the tumor control probability (TCP) and normal tissue complication probability (NTCP), respectively. The influence of the model parameter uncertainties on the TCP differences and the NTCP differences between AAA and AXB plans were studied by applying different sets of published model parameters. Patients were grouped into peripheral and centrally-located tumors to evaluate the impact of tumor location. RESULTS: PTV dose was lower in the re-calculated AXB plans, as compared to AAA plans. The median differences of PTV(D95%) were 1.7 Gy (range: 0.3, 6.5 Gy) and 1.0 Gy (range: 0.6, 4.4 Gy) for peripheral tumors and centrally-located tumors, respectively. The median differences of PTV(mean) were 0.4 Gy (range: 0.0, 1.9 Gy) and 0.9 Gy (range: 0.0, 4.3 Gy) for peripheral tumors and centrally located tumors, respectively. TCP was also found lower in AXB-recalculated plans compared with the AAA plans. The median (range) of the TCP differences for 30 month local control were 1.6 % (0.3 %, 5.8 %) for peripheral tumors and 1.3 % (0.5 %, 3.4 %) for centrally located tumors. The lower TCP is associated with the lower PTV coverage in AXB-recalculated plans. No obvious trend was observed between the calculation-resulted TCP differences and tumor size or location. AAA and AXB yield very similar NTCP on lung pneumonitis according to the LKB model estimation in the present study. CONCLUSION: AAA apparently overestimates the PTV dose; the magnitude of resulting difference in calculated TCP was up to 5.8 % in our study. AAA and AXB yield very similar NTCP on lung pneumonitis based on the LKB model parameter sets we used in the present study. PMID- 26800882 TI - Classification and characterization of human endogenous retroviruses; mosaic forms are common. AB - BACKGROUND: Human endogenous retroviruses (HERVs) represent the inheritance of ancient germ-line cell infections by exogenous retroviruses and the subsequent transmission of the integrated proviruses to the descendants. ERVs have the same internal structure as exogenous retroviruses. While no replication-competent HERVs have been recognized, some retain up to three of four intact ORFs. HERVs have been classified before, with varying scope and depth, notably in the RepBase/RepeatMasker system. However, existing classifications are bewildering. There is a need for a systematic, unifying and simple classification. We strived for a classification which is traceable to previous classifications and which encompasses HERV variation within a limited number of clades. RESULTS: The human genome assembly GRCh 37/hg19 was analyzed with RetroTector, which primarily detects relatively complete Class I and II proviruses. A total of 3173 HERV sequences were identified. The structure of and relations between these proviruses was resolved through a multi-step classification procedure that involved a novel type of similarity image analysis ("Simage") which allowed discrimination of heterogeneous (noncanonical) from homogeneous (canonical) HERVs. Of the 3173 HERVs, 1214 were canonical and segregated into 39 canonical clades (groups), belonging to class I (Gamma- and Epsilon-like), II (Beta-like) and III (Spuma-like). The groups were chosen based on (1) sequence (nucleotide and Pol amino acid), similarity, (2) degree of fit to previously published clades, often from RepBase, and (3) taxonomic markers. The groups fell into 11 supergroups. The 1959 noncanonical HERVs contained 31 additional, less well defined groups. Simage analysis revealed several types of mosaicism, notably recombination and secondary integration. By comparing flanking sequences, LTRs and completeness of gene structure, we deduced that some noncanonical HERVs proliferated after the recombination event. Groups were further divided into envelope subgroups (altogether 94) based on sequence similarity and characteristic "immunosuppressive domain" motifs. Intra and inter(super)group, as well as intraclass, recombination involving envelope genes ("env snatching") was a common event. LTR divergence indicated that HERV-K(HML2) and HERVFC had the most recent integrations, HERVL and HUERSP3 the oldest. CONCLUSIONS: A comprehensive HERV classification and characterization approach was undertaken. It should be applicable for classification of all ERVs. Recombination was common among HERV ancestors. PMID- 26800884 TI - Temporal genetic diversity of Schistosoma japonicum in two endemic sites in China revealed by microsatellite markers. AB - BACKGROUND: Schistosomiasis is one of the neglected tropical diseases. The causative agent of schistosomiasis in China, Schistosoma japonicum, has long been a major public health problem. An understanding of fundamental evolutionary and genetic processes in this species has major implications for its control and elimination. Intensive control efforts have greatly reduced the incidence of schistosomiasis in China, but little is known about the genetic consequences of these efforts. METHODS: To investigate this, we sampled twice (years 2003 and 2011) from two endemic regions where populations of S. japonicum had persisted despite control efforts and genotyped these samples using ten microsatellite markers. Our main hypothesis was that parasite genetic diversity would be greatly reduced across this time period. CONCLUSIONS: There was no apparent reduction in allelic diversity, and a non-significant reduction in clonal diversity in these parasite populations between 2003 and 2011. We did, however, detect temporal genetic differentiation among the samples. Such a significant temporal genetic variation of S. japonicum populations has not been reported before. PMID- 26800885 TI - HDR syndrome in a Japanese girl with biliary atresia: a case report. AB - BACKGROUND: Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder. We report the first detailed case of hypoparathyroidism complicated by biliary atresia. CASE PRESENTATION: A 1-year old Japanese girl was admitted to our hospital for living donor liver transplantation. She suffered from obstructive jaundice owing to biliary atresia. She also had persistent hypocalcemia. Despite oral calcium and abundant vitamin D supplementation, a laboratory test showed hypocalcemia (1.4 mmol/l) and hyperphosphatemia (2.6 mmol/l). The intact parathyroid hormone level was normal (66 ng/l) with severe vitamin D deficiency (25-hydroxy vitamin D: undetectable levels). There were no rachitic changes in metaphysis on X-rays. Her family history showed that her mother had sensorineural deafness, a low serum calcium level (2.1 mmol/l), hypoplastic left kidney, and a past history of an operation for right vesicoureteral reflux. We suspected that this patient and her mother have hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome. A heterozygous GATA3 gene mutation (c.736delGinsAT) was found in this patient and her mother, but not in her father. CONCLUSION: This familial case confirms the importance of family history in the diagnosis of HDR syndrome. Regardless of marked vitamin D deficiency, the complication of hypoparathyroidism prevented the onset of vitamin D deficiency rickets in our patient. PMID- 26800886 TI - The first genome sequence of a metatherian herpesvirus: Macropodid herpesvirus 1. AB - BACKGROUND: While many placental herpesvirus genomes have been fully sequenced, the complete genome of a marsupial herpesvirus has not been described. Here we present the first genome sequence of a metatherian herpesvirus, Macropodid herpesvirus 1 (MaHV-1). RESULTS: The MaHV-1 viral genome was sequenced using an Illumina MiSeq sequencer, de novo assembly was performed and the genome was annotated. The MaHV-1 genome was 140 kbp in length and clustered phylogenetically with the primate simplexviruses, sharing 67% nucleotide sequence identity with Human herpesviruses 1 and 2. The MaHV-1 genome contained 66 predicted open reading frames (ORFs) homologous to those in other herpesvirus genomes, but lacked homologues of UL3, UL4, UL56 and glycoprotein J. This is the first alphaherpesvirus genome that has been found to lack the UL3 and UL4 homologues. We identified six novel ORFs and confirmed their transcription by RT-PCR. CONCLUSIONS: This is the first genome sequence of a herpesvirus that infects metatherians, a taxonomically unique mammalian clade. Members of the Simplexvirus genus are remarkably conserved, so the absence of ORFs otherwise retained in eutherian and avian alphaherpesviruses contributes to our understanding of the Alphaherpesvirinae. Further study of metatherian herpesvirus genetics and pathogenesis provides a unique approach to understanding herpesvirus-mammalian interactions. PMID- 26800887 TI - Association of common variants identified by recent genome-wide association studies with obesity in Chinese children: a case-control study. AB - BACKGROUND: Large-scale genome-wide association studies have identified multiple genetic variants that are associated with elevated body mass index (BMI) or the risk of obesity in Caucasian or Asian populations. We examined whether these variants are individually associated with obesity in Chinese children, and also assessed their cumulative effects and predictive value for obesity risk in Chinese children. METHODS: We genotyped 40 single nucleotide polymorphisms (SNPs) and conducted association analyses for 32/40 SNPs with an estimated minor allele frequency >1% in 2 030 unrelated Chinese children, including 607 normal-weight, 718 overweight, and 705 obese individuals from two cross-sectional study groups. Logistic regression and linear regression under the additive model were used to examine associations, and the area under the receiver operating characteristic curve (AUCROC) was reported as prediction summary. RESULTS: We identified obesity association for 6 SNPs near SEC16B, RBJ, CDKAL1, TFAP2B, MAP2K5 and FTO (odds ratios (ORs) ranged from 1.19 to 1.41, nominal two-sided P-values < 0.05). Association (Bonferroni corrected) of rs543874 near SEC16B and rs2241423 near MAP2K5 had presumably stronger effects on obesity in Chinese children than in Caucasian populations. Their risk alleles were also associated with BMI standard deviation score (BMI-SDS) variability. We demonstrated the cumulative effects of the 32 SNPs on obesity risk (per risk allele: OR = 1.06, 95 % CI: 1.03-1.11, P = 4.84 * 10(-4)) and BMI-SDS (beta = 0.04, 95% CI: 0.02-0.06, P = 3.69 * 10(-7)). The difference in AUCROC for a model with covariates (age, age square, sex and study group) and the model including covariates and all 32 SNPs was 2.8% (P = 0.0002). CONCLUSION: While six SNPs were individually associated with obesity in Chinese children, the 32 common variants identified by recent GWA studies had cumulative effects and resulted in a limited increase in the AUCROC predictive value for childhood obesity. PMID- 26800888 TI - Intravitreal luxated lens stuck on the optic disc: a case report. AB - BACKGROUND: We encountered a rare patient with lens luxation in which the lens had become stuck on the optic disc. Findings obtained during vitreous surgery suggested that the luxated lens had become stuck on the optic disc via residual vitreous gel. CASE PRESENTATION: An 88-year-old Japanese man experienced lens luxation into the inferior vitreous cavity while undergoing treatment for glaucoma in his left eye. Because no inflammation was present upon examination, we observed the patient without prescribing any additional medications except for the eye drop treatment for glaucoma. Two years later, the patient revisited our clinic after suddenly noticing a visual disturbance in his left eye. A fundus examination revealed that the luxated lens had become stuck on the optic disc and displayed no changes in relation to the patient's head position or eye movement. Subsequently, vitreous surgery was performed to remove the luxated lens. During the surgery, we observed an aggregation of vitreous gel between the luxated lens and the optic disc. The luxated lens was successfully mobilized by pushing with a vitreous cutter and then extracted through a corneoscleral incision using perfluorocarbon liquid. At 4 months after surgery, the patient's visual acuity had improved to 20/25. CONCLUSIONS: The findings of this study suggest that the luxated lens had become stuck on the optic disc via residual vitreous gel on the optic disc. The surgical procedure of extracting the luxated lens through a corneoscleral incision using perfluorocarbon liquid was found to be both safe and effective. PMID- 26800889 TI - The effect of concentrating obstetrics services in fewer hospitals on patient access: a simulation. AB - BACKGROUND: In Japan, the number of obstetrics facilities has steadily decreased and the selection and concentration of obstetrics facilities is progressing rapidly. Obstetrics services should be concentrated in fewer hospitals to improve quality of care and reduce the workload of obstetricians. However, the impact of this intensification of services on access to obstetrics hospitals is not known. We undertook a simulation to examine how the intensification of obstetrics services would affect access to hospitals based on a variety of scenarios, and the implications for health policy. METHODS: The female population aged between 15 and 49 living within a 30-min drive of an obstetrics hospital was calculated using a Geographic Information System for three possible intensification scenarios: Scenario 1 retained facilities with a higher volume of deliveries without considering the geographic boundaries of Medical Service Areas (MSAs, zones of healthcare administration and management); Scenario 2 prioritized retaining at least one hospital in each MSA and then retained higher delivery volume institutions, while Scenario 3 retained facilities to maximize population coverage using location-allocation modeling. We also assessed the impact of concentrating services in academic hospitals and specialist perinatal medical centers (PMCs) alone. RESULTS: In 2011, 95.0% of women aged 15-49 years lived within a 30-min drive of one of 1075 obstetrics hospitals. This would fall to 82.7% if obstetrics services were intensified into academic hospitals and general and regional PMCs. If 55.0% of institutions provided obstetrics services, the coverage would be 87.6% in Scenario 1, whereas intensification based on access would achieve over 90.5% coverage in Scenario 2 and 93.9% in Scenario 3. CONCLUSIONS: Intensification of obstetrics facilities impairs access, but a greater caseload and better staffing have the potential advantages of better clinical outcomes and reduced costs. It is essential to consult residents of hospital catchment areas when reorganizing clinical services; a simulation is a useful means of informing these important discussions. PMID- 26800890 TI - Legal knowledge, needs, and assistance seeking among HIV positive and negative women in Umlazi, South Africa. AB - BACKGROUND: The rights of women and people living with HIV (PLHIV) are protected under South African law, yet there is a gap in the application of these laws. While there are numerous systemic and social barriers to women's and PLHIV's exercise of their legal rights and rights to access social services, there has been little effort to document these barriers as well as legal needs and knowledge in this context. METHODS: 1480 HIV-positive and HIV-negative women recruited from an antenatal clinic in Umlazi Township completed a questionnaire on legal knowledge, experience of legal issues, assistance seeking for legal issues, and barriers to seeking assistance. We compared the legal knowledge and experience of legal issues of HIV-positive and HIV-negative women, and described assistance seeking and barriers to assistance seeking among all women. RESULTS: Both HIV-positive and HIV-negative women had high levels of knowledge of their legal rights. There were few important differences in legal knowledge and experience of legal issues by HIV status. The most common legal issues women experienced were difficulty obtaining employment (11 %) and identification documents (7 %). A minority of women who had ever experienced a legal issue had sought assistance for this issue (38 %), and half (50 %) of assistance sought was from informal sources such as family and friends. Women cited lack of time and government bureaucracy as the major barriers to seeking assistance. CONCLUSIONS: These results indicate few differences in legal knowledge and needs between HIV positive and HIV-negative women in this context, but rather legal needs common among women of reproductive age. Legal knowledge may be a less important barrier to seeking assistance for legal issues than time, convenience, and cost. Expanding the power of customary courts to address routine legal issues, encouragement of pro bono legal assistance, and introduction of legal navigators could help to address these barriers. PMID- 26800891 TI - Association of household income and education with eating behaviors in Japanese adults: a cross-sectional study. AB - BACKGROUND: Socioeconomic inequalities as social determinants of health are important issues in public health and health promotion. However, the association between socioeconomic status and eating behaviors has been investigated poorly in Japanese adults. To fill this gap, the present study examines the association of eating behaviors with household income and education. METHODS: The sample comprised 3,137 Japanese adults (1,580 men and 1,557 women) aged 30 to 59 years who responded to an Internet-based cross-sectional survey in 2014. Data on the following eating behaviors were collected via self-report: "taking care of one's diet for health," "eating vegetables," "frequency of eating breakfast," "frequency of family breakfasts," "frequency of family dinners," "using the information on nutrition labels," and "conversations with family or friends during meals." Self-reported data on socioeconomic status (household income and education) and demographic variables (gender, age, district of residence, marital status, residence status, and employment status) were also collected. The associations between eating behaviors and household income or education were tested using binomial logistic regression analysis with eating behaviors as dependent variables and household income and education as independent variables. A trend P -value was calculated for three categories of household income (less than 3,000,000 JPY, 3,000,000-7,000,000 JPY, and over 7,000,000 JPY) and education (junior high/high school, 2-year college, and 4-year college/graduate school). RESULTS: Higher household income and education were significantly associated with higher rates of eating vegetables, using the information on nutrition labels, and conversation with family or friends during meals in Japanese men and women. Higher household incomes were significantly associated with lower rates of frequency of family breakfasts in Japanese men and lower rates of frequency of family dinners in Japanese men and women. CONCLUSIONS: Higher socioeconomic status as indicated by household income or education was associated with eating more vegetables and conversation with family or friends during meals in Japanese men and women. Socioeconomic status should be considered in health promotion and diet improvement. PMID- 26800892 TI - Apolipoprotein E gene polymorphism and risk of type 2 diabetes and cardiovascular disease. AB - BACKGROUND: Lipoprotein-related mechanisms have been associated with damage to the cardiovascular system in diabetic patients. Apolipoprotein E gene which affects the clearance of lipoproteins and consequently the lipid profile in our body is one of the most studied candidate genes and recently has been reported to be associated with T2DM and CAD. In this work, we studied the association of apoE gene polymorphism with T2DM and CVD and its effect on plasma lipids profile. METHODS: Our study was conducted on 284 subjects categorized into 100 patients with T2DM, 100 patients with T2DM complicated with CVD and 84 normal control subjects. ApoE gene polymorphism was genotyped by real-time PCR using TaqMan((r)) SNP Genotyping Assay. RESULTS: ApoE E3/E3 genotype was the most common in our subjects. The frequencies of E3/E4 genotype and epsilon4 allele were increased in both T2DM patients and CVD patients as compared with controls, but were significant only in CVD patients (p = 0.004 and 0.007, respectively). Diabetic patients who carried E3/E4 genotype were at 2.4-fold increased risk to develop CVD (95 % CI 1.14-5.19, P = 0.02) and the epsilon4 allele associated with 2.23 fold higher CVD risk (95 % CI 1.09-4.59, P = 0.02). After adjustment for other established risk factors, E3/E4 genotype was an independent risk factor for CVD (OR = 2.3, p = 0.009) but not for T2DM (OR = 1.7, p = 0.28), while epsilon4 allele was an independent risk factor for both T2DM (OR = 2.2, p = 0.04) and CVD (OR = 3.0, p = 0.018) with 5.9-fold increased risk to develop CVD in T2DM patients (p = 0.019). E3/E4 genotype associated with significantly higher levels of TC and non HDL-C in all groups and with significantly higher levels of LDL-C in both T2DM and CVD patients. CONCLUSIONS: ApoE gene polymorphisms associate with CVD and affect the lipid profile. The epsilon4 allele is an independent risk factor for both T2DM and CVD. Further genetic studies to add information beyond the traditional cardiovascular risk factors in T2DM and to identify risk genotypes will help in early prediction and identification of at risk patients. PMID- 26800894 TI - Total Worker Health(r): More Implications for the Occupational Health Nurse. PMID- 26800893 TI - Inhibitory effects of Cheongsangbangpoong-tang on both inflammatory acne lesions and facial heat in patients with acne vulgaris: A randomized controlled trial protocol. AB - BACKGROUND: Due to increasing interest from acne patients concerned about the side effects associated with conventional therapies, complementary and alternative medicine (CAM) has been suggested as a new therapeutic modality for acne vulgaris. Herbal medicine is one of these CAM treatments. Cheongsangbangpoong-tang (CBT) is a common herbal formula used in patients with acne vulgaris in the clinical practice of Korean Medicine (KM). However, despite the common use of CBT in clinical practice, the current level of evidence is insufficient to support an inhibitory effect of CBT on inflammatory acne lesions and facial heat. Therefore, this study was designed to assess the inhibitory effect of CBT on both inflammatory acne lesions and facial heat. METHODS/DESIGN: A randomized, double-blind, parallel-group, and placebo-controlled trial will be conducted. Fifty-six participants with acne vulgaris will be randomized into one of two groups: the CBT or placebo groups. After randomization, participants will be prescribed either CBT or placebo three times a day at a dose of 5 g after meals for 8 weeks. The following outcome measurements will be used in the examination of subjects: the mean percentage change and the count change of the inflammatory and non-inflammatory acne lesions, the temperature of facial points on digital infrared thermal imaging (DITI), serum cortisol, serum dehydroepiandrosterone-sulfate (DHEA-S), visual analogue scale (VAS), investigator global assessment (IGA), and severity score on the Korean Acne Grading System (KAGS) from baseline to the end of the trial. DISCUSSION: This trial will provide evidence regarding the inhibitory effect of CBT on inflammatory acne lesions and facial heat. The findings of this trial may have important implications for the more widespread use of CBT for the treatment of acne vulgaris. TRIAL REGISTRATION: The trial is registered with the Clinical Research Information Service (CRiS), Republic of Korea: KCT0001468 . PMID- 26800895 TI - The Impact of Language and Culture Diversity in Occupational Safety. AB - Occupational health nursing plays a critical part in improving the safety of foreign labor workers. The development and implementation of safety training programs do not always regularly take into account language barriers, low literacy levels, or cultural elements. This oversight can lead to more injuries and fatalities among this group. Despite established health and safety training programs, a significant number of non-native English speakers are injured or killed in preventable, occupation-related accidents. Introducing safety programs that use alternative teaching strategies such as pictograms, illustrations, and hands-on training opportunities will assist in addressing challenges for non English laborers. Occupational health nursing has an opportunity to provide guidance on this subject and assist businesses in creating a safer and more productive work environment. PMID- 26800896 TI - Bisphenol A: Understanding the Controversy. AB - Healthy People 2020 lists Bisphenol A (BPA) as a potential endocrine disruptor for which exposure should be reduced. The Healthy People 2020 Environmental Health Objectives focus on addressing environmental factors that negatively affect individuals' health even though the health effects of some toxic substances are not yet fully understood. An American Association of Occupational Health Nurses (AAOHN) position statement outlined the role occupational health nurses play in creating healthy and productive workplaces by promoting worker health. BPA is implicated in a variety of health outcomes such as breast and prostate cancer, menstrual irregularities, genital abnormalities in male babies, infertility in men and women, early puberty in girls, and metabolic disorders such as diabetes and obesity. The overall health issues attributed to BPA exposure are complex and controversial. Concerns regarding environmental health are growing as individuals become more dependent on plastics. Numerous health concerns have been directly connected to daily exposures to products manufactured with BPA. Government agencies support the use of BPA as a safe consumer product with the exception of BPA use in baby bottles and sippy cups, which has been banned in the United States and several other countries. Many agencies (e.g., Federal Drug Administration [FDA], World Health Organization [WHO], U.S. Department of Health & Human Services [U.S. DHHS], and the Centers for Disease Control and Prevention [CDC]) have expressed "some concern" about BPA based on research, and stated further research is warranted. PMID- 26800898 TI - Immunochemical studies on HNE-modified HSA: Anti-HNE-HSA antibodies as a probe for HNE damaged albumin in SLE. AB - Non-enzymatic lipid peroxidation of cellular membranes occurs during periods of sustained oxidative stress. 4-Hydroxynonenal (HNE), the most reactive lipid peroxidation product, is capable of modifying and/or cross-linking proteins leading to impaired physiological functions. The formation of protein adducts produce structural modifications which generate neo-antigens and induce auto antibodies. Enhanced oxidative stress and accumulation of HNE-modified proteins are associated with systemic lupus erythematosus (SLE) and other autoimmune diseases. This study has probed the role of lipid peroxidation derived aldehydes in SLE. We report the structural perturbations in human serum albumin (HSA) upon modification with HNE and the consequential enhanced immunogenicity. The induced antibodies were found to be highly specific for the immunogen and exhibited cross reactivity with HNE-modified epitopes on proteins, amino acids and nucleic acid. The experimentally induced anti-HNE-HSA antibodies appreciably recognized HNE modified epitopes on the HSA obtained from SLE patients. These antibodies, therefore, form a good immunochemical probe to detect such damages in lupus patients. Possible role of anti-HNE-HSA antibodies as a marker for detection/progression of SLE has been discussed. PMID- 26800899 TI - Biopolymer capped silver nanoparticles with potential for multifaceted applications. AB - A sustainable, green and low cost method for the synthesis of silver nanoparticles at room temperature has been developed using guargum as a reducing and stabilizing agent. The synthesized silver nanoparticles (GAg) were characterized by UV-vis spectroscopy, FTIR, EDS, Raman, XRD and TEM. The interaction of the functional groups present in the biopolymer Guargum (G) with the silver nanoparticles (GAg) were responsible for the nanoparticle surface to function as active substrates for Surface Enhanced Raman Spectroscopic (SERS) detection of cationic and anionic dyes. The catalytic degradation of a copper phthalocyanine based dye- Reactive blue - 21(RB-21), an azo dye- Reactive red 141(RR-141) and a xanthene dye- Rhodamine - 6G(Rh-6G) as well as binary mixtures of the three dyes was evaluated using the synthesized nanoparticles. The catalyst also caused a significant reduction in Total Organic Carbon (TOC) suggesting the formation of smaller degraded products. PMID- 26800900 TI - Some physicochemical and rheological properties of starch isolated from avocado seeds. AB - Seeds from avocado (Persea americana Miller) fruit are a waste byproduct of fruit processing. Starch from avocado seed is a potential alternative starch source. Two different extraction solvents were used to isolate starch from avocado seeds, functional and rheological characteristics measured for these starches, and comparisons made to maize starch. Avocado seed powder was suspended in a solution containing 2 mM Tris, 7.5 mM NaCl and 80 mM NaHSO3 (solvent A) or sodium bisulphite solution (1500 ppm SO2, solvent B). Solvent type had no influence (p>0.05) on starch properties. Amylose content was 15-16%. Gelatinization temperature range was 56-74 degrees C, peak temperature was 65.7 degrees C, and transition enthalpy was 11.4-11.6J/g. At 90 degrees C, solubility was 19-20%, swelling power 28-30 g water/g starch, and water absorption capacity was 22-24 g water/g starch. Pasting properties were initial temperature 72 degrees C; maximum viscosity 380-390 BU; breakdown -2 BU; consistency 200 BU; and setback 198 BU. Avocado seed starch dispersions (5% w/v) were characterized as viscoelastic systems, with G'>G". Avocado seed starch has potential applications as a thickening and gelling agent in food systems, as a vehicle in pharmaceutical systems and an ingredient in biodegradable polymers for food packaging. PMID- 26800901 TI - Degradation of chondroitin sulfate by the gut microbiota of Chinese individuals. AB - Oral preparations of chondroitin sulfate (CS) have long been used as anti osteoarthritis (anti-OA) drugs. However, little is known about the degradation of CS by human gut microbiota. In the present study, degradation profiles of CSA (the main constituent of CS drugs) by the human gut microbiota from six healthy subjects were investigated. Each individual's microbiota had differing degradation activities, but DeltaUA-GalNAc4S was the end product in all cases. To elucidate the mechanisms underlying this phenomenon, different CSA-degrading bacteria were isolated from each individual's microbiota and tested for CSA degradation. In addition to Bacteroides thetaiotaomicron J1, Bacteroides thetaiotaomicron 82 and Bacteroides ovatus E3, a new CSA-degrading bacterium, Clostridium hathewayi R4, was isolated and characterized. Interestingly, at least two different CSA-degrading species were identified from each individual's gut microbiota. Predictably, these functional bacteria also had differing degradation rates, but still generated the same end product, DeltaUA-GalNAc4S. In addition, the human fecal isolates produced different degradation profiles for CSC, CSD, and CSE, suggesting that CS could be readily metabolized to varying extents by diverse microbial consortiums, which may help to explain the poor bioavailability and unequal efficacy of CS among individuals in OA treatment. PMID- 26800902 TI - Charged pullulan derivatives for the development of nanocarriers by polyelectrolyte complexation. AB - Pullulan, a neutral polysaccharide, was chemically modified in order to obtain two charged derivatives: reaction with SO3(.)DMF complex afforded a sulfate derivative (SP), while reaction with glycidyltrimethylammonium chloride gave a quaternary ammonium salt (AP). The presence of the charged groups was confirmed by FTIR. Assessment of the positions where the reaction took place was based on (1)H- and (13)C NMR (COSY, HSQC-TOCSY, HSQC-DEPT, and HMBC) experiments. Estimation of the degree of substitution (DS) was made from elemental analysis data, and further confirmed by NMR peak areas in the case of AP. These new derivatives showed the capability to condense with each other, forming nanoparticles with the ability to associate a model protein (BSA) and displaying adequate size for drug delivery applications, therefore making them good candidates for the production of pullulan-based nanocarriers by polyelectrolyte complexation. PMID- 26800903 TI - Computerized Tailored Interventions to Enhance Prevention and Screening for Hepatitis C Virus Among People Who Inject Drugs: Protocol for a Randomized Pilot Study. AB - BACKGROUND: Hepatitis C virus (HCV) infection is a growing problem among people who inject drugs. Strategies to reduce disease transmission (eg, syringe exchange programs) and facilitate HCV screening and linkage are available but are under utilized in many communities affected by injection drug use. Novel approaches to increasing the use of these strategies are needed. OBJECTIVE: The goals of this project are to (1) develop and pilot test a computerized tailored intervention for increasing HCV screening and decreasing risky drug use behavior among people who inject drugs and (2) determine the feasibility of disseminating such an intervention using peer-based referrals in the setting of a community-based syringe exchange program. METHODS: This 2-arm, randomized pilot study is being conducted in a large-volume, multisite syringe exchange program in southern Wisconsin. A social network-based strategy was used to recruit a total of 235 adults who reported past-month injection of opioids, cocaine, or methamphetamine. Network recruiters were identified among clients requesting services from the syringe exchange program and were enlisted to refer eligible peers to the study. All participants completed a computer-adapted questionnaire eliciting information about risk behaviors and their knowledge, attitudes, and prior experiences related to HCV screening. Subjects were then randomly assigned to receive usual care, consisting of standard counseling by syringe exchange staff, or the Hep-Net intervention, which provides algorithm-based, real-time tailored feedback and recommendations for behavior change in the style of motivational interviewing. Changes in drug use behaviors and attitudes will be assessed during a second session between 90 and 180 days after the baseline visit. Frequency of repeat HCV testing and HCV incidence will be assessed through a database search 1 year after study completion. RESULTS: Recruitment for this study was completed in April 2015. Follow-up of enrolled participants is expected to continue until March 2016. Network recruiters were enrolled who referred a total of 195 eligible peers (overall N=235). At baseline, the median age was 34 years; 41.3% (97/235) were non-white; and 86.4% (203/235) reported predominantly injecting heroin. Most participants (161/234, 68.8%) reported sharing injection equipment in the past and of these, 30.4% (49/161) had never been tested for HCV. CONCLUSIONS: This study will provide preliminary evidence to determine whether incorporating computerized behavioral interventions into existing prevention services at syringe exchange programs can lead to adoption of healthier behaviors. TRIAL REGISTRATION: ClinicalTrials.gov NCT02474043; https://clinicaltrials.gov/ct2/show/NCT02474043 (Archived by WebCite at http://www.webcitation.org/6dbjUQG7J). PMID- 26800961 TI - Understanding how prevocational training on care farms can lead to functioning, motivation and well-being. AB - PURPOSE: Prevocational training aims to improve basic vocational and social skills, supporting return to work for people who have been out of work for a long time. Care farms provide prevocational training; the aim of the study was to use the self-determination theory to gain an understanding of how these programmes can lead to healthy functioning and motivation for clients. METHOD: A total of 194 participants in prevocational training on care farms answered questions about demographic information, their perception of being a colleague, the social community on the farm, experiencing nature and animals and need satisfaction. A cross-sectional design resulting in a structural equation model was used to understand how elements of the care farm context influence satisfaction of three psychological needs. RESULTS: The results showed that a feeling of being a useful colleague led to competence, experiencing a sense of group belonging led to relatedness and autonomy, while receiving social support from the farmer led to satisfaction of all three needs for the participants. CONCLUSIONS: The results explain how prevocational training can stimulate participants' functionality, motivation and well-being. This understanding enables initiators and managers of prevocational training to understand and further strengthen the need-supportive elements of such programmes. Implications for Rehabilitation Prevocational training on care farms can facilitate motivation, functioning and well-being for clients. Making clients feel like useful colleagues that belong to a client group will strengthen the positive qualities of these programmes. Support, understanding and acknowledgement from the farmer are the most important elements for a positive development for the clients. PMID- 26800962 TI - Distress, Dependency, and Threat in Newly Diagnosed Cancer and Heart Disease Patients. AB - The effects of life-threatening illness on 56 lung cancer and 65 heart attack patients at one and two months postdiagnosis were assessed with objective self report inventories measuring symptom distress, social dependency, concerns, mood, personality, and evaluation of problem management. Lung cancer patients had more symptom distress and concerns, and evaluated themselves more harshly, than heart attack patients. Although symptom distress remained unchanged, both kinds of patients reported significant improvement in mood and concerns by the second month postdiagnosis; this improvement was interpreted as a result of assimilating the life-threatening aspects of these diseases. Structural equation models of individual differences suggested that, even though the two groups were characterized by mean differences, the causal processes within the two groups were similar, with symptom distress the most pervasive and powerful influence. The importance of conducting both individual differences and group differences analyses was stressed. PMID- 26800963 TI - Small Sample Confidence Bounds on Measures of Agreement of Confusion Matrices. AB - Tau, Lambda, and Kappa are measures developed for the analysis of discrete multivariate data of the type represented by stimulus response confusion matrices. The accuracy with which they may be estimated from small sample confusion matrices is investigated by Monte Carlo methods. Results show that Kappa and Lambda are covered by their confidence intervals more frequently than is Tau. Although most of the intervals are too short for small samples, resulting in fewer than expected hits by the confidence bounds, Kappa and Lambda appear to be quite usable for even very small sample sizes. PMID- 26800964 TI - Changing a Causal Hypothesis without Changing the Fit: some Rules for Generating Equivalent Path Models. AB - Since computer programs have been available for estimating and testing linear causal models (e.g. LISREL by Joreskog & Sorbom) these models have been used increasingly in the behavioral sciences. This paper discusses the problem that very different causal structures may fit the same set of data equally well. Equivalence of models is defined as undecidability in principle and four rules are presented showing how equivalent models may be generated. Rules I and II refer to inversions in the causal order of variables and Rules III and IV to replacements of paths by the assumption of correlated residuals. Three examples are given to illustrate how the rules are applied. PMID- 26800965 TI - Motivating and Stressful Properties of Jobs: Integration of Research Approaches Through Facet Analysis. AB - This study applied the methodology of Facet Analysis in order to develop and test a definitional framework for the study of job characteristics. Five facets were used to define job characteristics, integrating the motivational and stressful properties of jobs. Perceptual responses were compared to attitudinal assessments. Analysis of the correlational structures of responses from a sample of 240 executives using Smallest Space Analysis supported the definitional system. The empirical data verified the five facets. Results indicated that the structure of relationships among job elements remains invariant across the three assessments of perception, importance, and satisfaction. PMID- 26800966 TI - On the Location of the Sensation Seeking construct in the Personality Domain. AB - The purpose of the study was to examine the location of Zuckerman's sensation seeking (SS) construct in the personality domain as measured by Cattell's 16 personality factors (16PF). The results of the factor analytic study indicated that the global construct of sensation seeking is related to the broad personality factor of independence. When the Sensation Seeking Scale (SSS) was divided into subscales, relations with two other broader personality factors, superego and pathemia, emerged as well. Nevertheless, the relationship with independence remained the most dominant one. The results of the present study seem to locate the sensation-seeking construct in the personality domain more precisely than previous findings. PMID- 26800967 TI - Factor Recovery in Binary Data Sets: A Simulation. AB - The present study compares the performance of phi coefficients and tetrachorics along two dimensions of factor recovery in binary data. These dimensions are (a) accuracy of nontrivial factor identification, and (b) factor structure recovery given a priori knowledge of the correct number of factors to rotate. Nontrivial factor identification was poor for both indices, with phi's performing slightly better than tetrachorics. In contrast, factor structure recovery was quite good when the correct number of factors was rotated. Phi coefficients generally yielded better factor structure recovery than tetrachorics and were better at preventing items from intruding onto factors where they did not belong, while tetrachorics were better than phi's at preventing items from being omitted from factors where they should have been included. The solutions based on tetrachorics contained many Heywood cases. It is suggested that for most applications it is preferable to base factor analysis on phi coefficients. PMID- 26800968 TI - Notes and Commentary: Regression Equations for the Latent Roots of Random Data Correlation Matrices with Unities on the Diagonal. AB - In order to make parallel analysis more accessible to researchers employing principal component techniques, regression equations are presented for the logarithms of the latent roots of random data correlation matrices with unities on the diagonal. These regression equations have as independent variables logarithms of: the single variable degrees of freedom; Bartlett-Lawley degrees of freedom; the next lowest ordered eigenvalue. The multiple correlation coefficients are at least 0.96 in all cases. PMID- 26800970 TI - IgA nephropathy and infections. AB - In this paper we concentrate on the role of infections in IgA nephropathy both from a pathogenetic and clinic point of view. The current hypotheses as regards the role of infections in the pathogenesis of IgA nephropathy are: (a) role of particular pathogens, (b) chronic exposure to mucosal infections, (c) abnormal handling of commensal microbes (gut microbiota). We also focus on particular infections reported in association with classic IgA nephropathy (HIV, malaria, Chlamydia, Lyme disease), as well as on IgA dominant-infection-associated glomerulonephritis. This is a unique form of glomerulonephritis, where IgA deposition is dominant. It is mostly recognized in old, diabetic patients and in association with staphylococcal infection. PMID- 26800971 TI - Metformin associated lactic acidosis (MALA): clinical profiling and management. AB - Metformin (MF) accumulation during acute kidney injury is associated with high anion gap lactic acidosis type B (MF-associated lactic acidosis, MALA), a serious medical condition leading to high mortality. Despite dose adjustment for renal failure, diabetic patients with chronic kidney disease (CKD) stage III-IV are at risk for rapid decline in renal function by whatever reason, so that MF toxicity might arise if the drug is not timely withdrawn. Sixteen consecutive patients were admitted to our Hospital's Emergency Department with clinical findings consistent with MALA. Fifteen had prior history of CKD, 60 % of them with GFR between 30 and 60 ml/min. Of these, 5 required mechanical ventilation and cardiovascular support; 3 promptly recovered renal function after rehydration, whereas 10 (62 %) required continuous veno-venous renal replacement treatment. SOFA and SAPS II scores were significantly related to the degree of lactic acidosis. In addition, lactate levels were relevant to therapeutic choices, since they were higher in dialyzed patients than in those on conservative treatment (11.92 mmol/l vs 5.7 mmol/l, p = 0.03). The overall death rate has been 31 %, with poorer prognosis for worse acidemia, as serum pH was significantly lower in non-survivors (pH 6.96 vs 7.16, p > 0.04). Our own data and a review of the literature suggest that aged, hemodynamically frail patients, with several comorbidities and CKD, are at greater risk of MALA, despite MF dosage adjustment. Moreover, renal replacement therapy rather than simple acidosis correction by administration of alkali seems the treatment of choice, based on eventual renal recovery and overall outcome. PMID- 26800973 TI - Gypenosides alleviate myocardial ischemia-reperfusion injury via attenuation of oxidative stress and preservation of mitochondrial function in rat heart. AB - Gypenosides (GP) are the predominant components of Gynostemma pentaphyllum, a Chinese herb medicine that has been widely used for the treatment of chronic inflammation, hyperlipidemia, and cardiovascular disease. GP has been demonstrated to exert protective effects on the liver and brain against ischemia reperfusion (I/R) injury, yet whether it is beneficial to the heart during myocardial I/R is unclear. In this study, we demonstrate that pre-treatment with GP dose-dependently limits infarct size, alleviates I/R-induced pathological changes in the myocardium, and preserves left ventricular function in a rat model of cardiac I/R injury. In addition, GP pre-treatment reduces oxidative stress and protects the intracellular antioxidant machinery in the myocardium. Further, we show that the cardioprotective effect of GP is associated with the preservation of mitochondrial function in the cardiomyocytes, as indicated by ATP level, enzymatic activities of complex I, II, and IV on the mitochondrial respiration chain, and the activity of citrate synthase in the citric acid cycle for energy generation. Moreover, GP maintains mitochondrial membrane integrity and inhibits the release of cytochrome c from the mitochondria to the cytosol. The cytoprotective effect of GP is further confirmed in vitro in H9c2 cardiomyoblast cell line with oxygen-glucose deprivation and reperfusion (OGD/R), and the results indicate that GP protects cell viability, reduces oxidative stress, and preserves mitochondrial function. In conclusion, our study suggests that GP may be of clinical value in cytoprotection during acute myocardial infarction and reperfusion. PMID- 26800972 TI - Phosphate binders in chronic kidney disease: a systematic review of recent data. AB - Hyperphosphatemia is common in chronic kidney disease (CKD) and is treated by dietary measures, dialysis techniques and/or phosphate binders. For the present review PubMed was searched for new publications on phosphate binders appearing between January 2010 and October 2015. This review summarizes the latest information on non-pharmacological measures and their problems in lowering phosphate in CKD patients, effects of phosphate binders on morbidity and mortality, adherence to phosphate binder therapy as well as new information on specific aspects of the various phosphate binders on the market: calcium acetate, calcium carbonate, magnesium-containing phosphate binders, polymeric phosphate binders (sevelamer, bixalomer, colestilan), lanthanum carbonate, ferric citrate, sucroferric oxyhydroxide, aluminum-containing phosphate binders, and new compounds in development. The review also briefly covers the emerging field of drugs targeting intestinal phosphate transporters. PMID- 26800974 TI - Teaching to Relax: Development of a Program to Potentiate Stress-Results of a Feasibility Study with Medical Undergraduate Students. AB - Medical students are a population at risk for the development of stress-related risk states (e.g. burnout) and manifest mental disorders (e.g. depression). Still the learning of coping mechanisms against stress is not an integral part of the medical curriculum. In a pilot study we developed an elective course for learning relaxation techniques (Relacs) which was geared to the clinical practice of autogenic training (AT) with psychiatric patients. The course focussed on an innovative and mostly communicative transfer of knowledge about AT, progressive muscle relaxation and medical hypnosis and stressed the principle of repeated and supervised exercises in small student groups alongside self-administered exercise. 42 students took part in this course and showed a very high acceptance for the topic and positive evaluation. Moreover, we found a distinct improvement of the participants' mental parameters (burnout, anxiety) and a good knowledge about the course's contents within the final exams at the end of the semester. The structure and realisation of the course is easily adaptable and very effective regarding the improvement of the students' mental health. Due to our results and the commonly known prevalence of stress-related disorders in medical students we postulate the integration of courses on relaxation strategies in the medical curriculum. PMID- 26800975 TI - Developing a Community-Based Participatory Research Approach to Understanding of the Repeat Use of Psychiatric Emergency Services. AB - Psychiatric emergency services (PES) remain a critical and under-examined component of the community mental health system. We describe how a unique community-academic partnership came together to examine repeat use of PES through the design and conduct of a qualitative study using a CBPR approach. The goals of the project were to: (1) develop a model of research which promoted the inclusion of people who use mental health services in the research process; and (2) design and conduct a study to examine the repeat use of PES through the inclusion of the perspectives and experiences of people who use these services. PMID- 26800976 TI - Control of brown patch (Rhizoctonia solani) in tall fescue (Festuca arundinacea Schreb.) by host induced gene silencing. AB - KEY MESSAGE: Transgenic tall fescue plants expressing RNAi constructs of essential genes of Rhizoctonia solani were resistant to R. solani. Tall fescue (Festuca arundinacea Schreb.) is an important turf and forage grass species widely used for home lawns and on golf courses in North Carolina and other transition zone states in the US. The most serious and frequently occurring disease of tall fescue is brown patch, caused by a basidiomycete fungus, Rhizoctonia solani. This research demonstrates resistance to brown patch disease achieved by the application of host induced gene silencing. We transformed tall fescue with RNAi constructs of four experimentally determined "essential" genes from R. solani (including genes encoding RNA polymerase, importin beta-1 subunit, Cohesin complex subunit Psm1, and a ubiquitin E3 ligase) to suppress expression of those genes inside the fungus and thus inhibit fungal infection. Four gene constructs were tested, and 19 transgenic plants were obtained, among which 12 plants had detectable accumulation of siRNAs of the target genes. In inoculation tests, six plants displayed significantly improved resistance against R. solani. Lesion size was reduced by as much as 90 %. Plants without RNAi accumulation did not show resistance. To our knowledge, this is the first case that RNAi constructs of pathogen genes introduced into a host plant can confer resistance against a necrotrophic fungus. PMID- 26800978 TI - Tuning interionic interaction by rationally controlling solution pH for highly selective colorimetric sensing of arginine. AB - Direct selective sensing of arginine in central nervous systems remains very essential to understanding of the molecular basis of some physiological events. This study presents the first demonstration on a simple yet effective method for arginine sensing with gold nanoparticles (Au-NPs) as the signal readout. The rationale for the method is based on the pH-dependent feature of the interionic interaction between cysteine and arginine. At pH 6.0, cysteine can only interact with arginine through the ion-pair interaction and such interaction can lead to the changes in both the solution color and UV-vis spectrum of the cysteine protected Au-NPs upon the addition of arginine. These changes are further developed into an analytical strategy for effective sensing of arginine by rationally controlling the pH values of Au-NP dispersions with the ratio of the absorbance at 650 nm (A 650) to that at 520 nm (A 520) (A 650/A 520) as a parameter for analysis. The method is responsive to arginine without the interference from other species in the cerebral system; under the optimized conditions, the A 650/A 520 values are linear with the concentration of arginine within a concentration range from 0.80 to 64 MUM, yet remain unchanged with the addition of other kinds of amino acids or the species in the central nervous system into the Au-NPs dispersion containing cysteine. The method demonstrated here is reliable and robust and could thus be used for detection of the increase of arginine in central nervous systems. PMID- 26800977 TI - Development of interspecies hybrids to increase ginseng biomass and ginsenoside yield. AB - KEY MESSAGE: Interspecific hybrids between Panax ginseng and P. quinquefolius results in hybrid vigor and higher ginsenoside contents. Ginseng is one of the most important herbs with valued pharmaceutical effects contributing mainly by the presence of bioactive ginsenosides in the roots. However, ginseng industry is impeded largely by its biological properties, because ginseng plants are slow growing perennial herbs with lower yield. To increase the ginseng yield and amounts of ginsenosides, we developed an effective ginseng production system using the F(1) progenies obtained from the interspecific reciprocal cross between two Panax species: P. ginseng and P. quinquefolius. Although hybrid plants show reduced male fertility, F(1) hybrids with the maternal origin either from P. ginseng or P. quinquefolius displayed heterosis; they had larger roots and higher contents of ginsenosides as compared with non-hybrid parental lines. Remarkably, the F(1) hybrids with the maternal origin of P. quinquefolius had much higher ginsenoside contents, especially ginsenoside Re and Rb1, than those with the maternal origin of P. ginseng. Additionally, non-targeted metabolomic profiling revealed a clear increase of a large number of primary and secondary metabolites including fatty acids, amino acids and ginsenosides in hybrid plants. To effectively identify the F(1) hybrids for the large-scale cultivation, we successfully developed a molecular marker detection system for discriminating F(1) reciprocal hybrids. In summary, this work provided a practical system for reciprocal hybrid ginseng production, which would facilitate the ginseng production in the future. PMID- 26800979 TI - Recent trends in the analysis of bioactive peptides in milk and dairy products. AB - Food-derived constituents represent important sources of several classes of bioactive compounds. Among them peptides have gained great attention in the last two decades thanks to the scientific evidence of their beneficial effects on health in addition to their established nutritional value. Several functionalities for bioactive peptides have been described, including antioxidative, antihypertensive, anti-inflammatory, immunomodulatory, and antimicrobial activity. They are now considered as novel and potential dietary ingredients to promote human health, though in some cases they may also have detrimental effects on health. Bioactive peptides can be naturally occurring, produced in vitro by enzymatic hydrolysis, and formed in vivo during gastrointestinal digestion of proteins. Thus, the need to gain a better understanding of the positive health effects of food peptides has prompted the development of analytical strategies for their isolation, separation, and identification in complex food matrices. Dairy products and milk are potential sources of bioactive peptides: several of them possess extra-nutritional physiological functions that qualify them to be classified under the functional food label. In this trends article we briefly describe the state-of-the-art of peptidomics methods for the identification and discovery of bioactive peptides, also considering recent progress in their analysis and highlighting the difficulty in the analysis of short amino acid sequences and endogenous peptides. PMID- 26800980 TI - NanoESI-MS-based lipidomics to discriminate between cultivars, cultivation ages, and parts of Panax ginseng. AB - Korean ginseng (Panax ginseng C.A. Meyer) is one of the most popular medicinal herbs used in Asia, including Korea and China. In the present study lipid profiling of two officially registered cultivars (P. ginseng 'Chunpoong' and P. ginseng 'Yunpoong') was performed at different cultivation ages (5 and 6 years) and on different parts (tap roots, lateral roots, and rhizomes) using nano electrospray ionization-mass spectrometry (nanoESI-MS). In total, 30 compounds including galactolipids, phospholipids, triacylglycerols, and ginsenosides were identified. Among them, triacylglycerol 54:6 (18:2/18:2/18:2), phosphatidylglycerol 34:3 (16:0/18:3), monogalactosyldiacylglycerol 36:4 (18:2/18:2), phosphatidic acid species 36:4 (18:2/18:2), and 34:1 (16:0/18:1) were selected as biomarkers to discriminate cultivars, cultivation ages, and parts. In addition, an unknown P. ginseng sample was successfully predicted by applying validated partial least squares projection to latent structures regression models. This is the first study regarding the identification of intact lipid species from P. ginseng and to predict cultivars, cultivation ages, and parts of P. ginseng using nanoESI-MS-based lipidomic profiling with a multivariate statistical analysis. PMID- 26800981 TI - A simple isotopic labeling method to study cysteine oxidation in Alzheimer's disease: oxidized cysteine-selective dimethylation (OxcysDML). AB - Cysteine is widely involved in redox signaling pathways through a number of reversible and irreversible modifications. Reversible modifications (e.g., S glutathionylation, S-nitrosylation, disulfide bonds, and sulfenic acid) are used to protect proteins from oxidative attack and maintain cellular homeostasis, while irreversible oxidations (e.g., sulfinic acid and sulfonic acid) serve as hallmarks of oxidative stress. Proteomic analysis of cysteine-enriched peptides coupled with reduction of oxidized thiols can be used to measure the oxidation states of cysteine, which is helpful for elucidating the role that oxidative stress plays in biology and disease. As an extension of our previously reported cysDML method, we have developed oxidized cysteine-selective dimethylation (OxcysDML), to investigate the site-specific total oxidation of cysteine residues in biologically relevant samples. OxcysDML employs (1) blocking of free thiols by a cysteine-reactive reagent, (2) enrichment of peptides containing reversibly oxidized cysteine by a solid phase resin, and (3) isotopic labeling of peptide amino groups to quantify cysteine modifications arising from different biological conditions. On-resin enrichment and labeling minimizes sample handing time and improves efficiency in comparison with other redox proteomic methods. OxcysDML is also inexpensive and flexible, as it can accommodate the exploration of various cysteine modifications. Here, we applied the method to liver tissues from a late stage Alzheimer's disease (AD) mouse model and wild-type (WT) controls. Because we have previously characterized this proteome using the cysDML approach, we are able here to probe deeper into the redox status of cysteine in AD. OxcysDML identified 1129 cysteine sites (from 527 proteins), among which 828 cysteine sites underwent oxidative modifications. Nineteen oxidized cysteine sites had significant alteration levels in AD and represent proteins involved in metabolic processes. Overall, we have demonstrated OxcysDML as a simple, rapid, robust, and inexpensive redox proteomic approach that is useful for gaining deeper insight into the proteome of AD. PMID- 26800982 TI - Recent advances in the development of capillary electrophoresis methodologies for optimizing, controlling, and characterizing the synthesis, functionalization, and physicochemical, properties of nanoparticles. AB - This paper gives a critical overview of capillary electrophoresis (CE) methodologies recently developed for controlling and optimizing the synthesis of nanoparticles as well as characterizing their functionalization in terms of physicochemical properties. Thanks to their electrophoretic mobility, various parameters can be determined, such as NP size and charge distribution, zeta potential, surface functionality, colloidal stability, grafting rates, and dissociation constants, allowing not only the complete characterization of new nanoprobes but also helping in their design and in the selection of chemical conditions for their storage and further manipulation. New strategies for the improvement of CE detection sensitivity are also described. PMID- 26800983 TI - Preexisting semantic representation improves working memory performance in the visuospatial domain. AB - Working memory (WM) for spoken language improves when the to-be-remembered items correspond to preexisting representations in long-term memory. We investigated whether this effect generalizes to the visuospatial domain by administering a visual n-back WM task to deaf signers and hearing signers, as well as to hearing nonsigners. Four different kinds of stimuli were presented: British Sign Language (BSL; familiar to the signers), Swedish Sign Language (SSL; unfamiliar), nonsigns, and nonlinguistic manual actions. The hearing signers performed better with BSL than with SSL, demonstrating a facilitatory effect of preexisting semantic representation. The deaf signers also performed better with BSL than with SSL, but only when WM load was high. No effect of preexisting phonological representation was detected. The deaf signers performed better than the hearing nonsigners with all sign-based materials, but this effect did not generalize to nonlinguistic manual actions. We argue that deaf signers, who are highly reliant on visual information for communication, develop expertise in processing sign based items, even when those items do not have preexisting semantic or phonological representations. Preexisting semantic representation, however, enhances the quality of the gesture-based representations temporarily maintained in WM by this group, thereby releasing WM resources to deal with increased load. Hearing signers, on the other hand, may make strategic use of their speech-based representations for mnemonic purposes. The overall pattern of results is in line with flexible-resource models of WM. PMID- 26800985 TI - CE-UV for the characterization of passion fruit juices provenance by amino acids profile with the aid of chemometric tools. AB - A separation method was developed in order to quantify free amino acids in passion fruit juices using CE-UV. A selective derivatization reaction with FMOC followed by MEKC analysis was chosen due to the highly interconnected mobilities of the analytes, enabling the separation of 22 amino acids by lipophilicity differences, as will be further discussed. To achieve such results, the method was optimized concerning BGE composition (concentrations, pH, and addition of organic modifier) and running conditions (temperature and applied voltage). The optimized running conditions were: a BGE composed by 60 mmol/L borate buffer at pH 10.1, 30 mmol/L SDS and 5 % methanol; running for 40 min at 23 degrees C and 25 kV. The method was validated and applied on eight brands plus one fresh natural juice, detecting 12 amino acids. Quantification of six analytes combined with principal component analysis was capable to characterize different types of juices and showed potential to detect adulteration on industrial juices. Glutamic acid was found to be the most concentrated amino acid in all juices, exceeding 1 g/L in all samples and was also crucial for the correct classification of a natural juice, which presented a concentration of 22 g/L. PMID- 26800984 TI - Inhibition of MMP-9 attenuates hypertensive cerebrovascular dysfunction in Dahl salt-sensitive rats. AB - Hypertensive cerebropathy is a pathological condition associated with cerebral edema and disruption of the blood-brain barrier. However, the molecular pathways leading to this condition remains obscure. We hypothesize that MMP-9 inhibition can help reducing blood pressure and endothelial disruption associated with hypertensive cerebropathy. Dahl salt-sensitive (Dahl/SS) and Lewis rats were fed with high-salt diet for 6 weeks and then treated without and with GM6001 (MMP inhibitor). Treatment of GM6001 (1.2 mg/kg body weight) was administered through intraperitoneal injections on alternate days for 4 weeks. GM6001 non-administered groups were given vehicle (0.9% NaCl in water) treatment as control. Blood pressure was measured by tail-cuff method. The brain tissues were analyzed for oxidative/nitrosative stress, vascular MMP-9 expression, and tight junction proteins (TJPs). GM6001 treatment significantly reduced mean blood pressure in Dahl/SS rats which was significantly higher in vehicle-treated Dahl/SS rats. MMP 9 expression and activity was also considerably reduced in GM6001-treated Dahl/SS rats, which was otherwise notably increased in vehicle-treated Dahl/SS rats. Similarly MMP-9 expression in cerebral vessels of GM6001-treated Dahl/SS rats was also alleviated, as devised by immunohistochemistry analysis. Oxidative/nitrosative stress was significantly higher in vehicle-treated Dahl/SS rats as determined by biochemical estimations of malondialdehyde, nitrite, reactive oxygen species, and glutathione levels. RT-PCR and immunohistochemistry analysis further confirmed considerable alterations of TJPs in hypertensive rats. Interestingly, GM6001 treatment significantly ameliorated oxidative/nitrosative stress and TJPs, which suggest restoration of vascular integrity in Dahl/SS rats. These findings determined that pharmacological inhibition of MMP-9 in hypertensive Dahl-SS rats attenuate high blood pressure and hypertension associated cerebrovascular pathology. PMID- 26800986 TI - Sensitivity of six subantarctic marine invertebrates to common metal contaminants. AB - A long history of anthropogenic activities in the relatively pristine subantarctic has resulted in areas of accumulated waste and contaminants. Sensitivities to metals of subantarctic and Antarctic species may contrast with related species from temperate and tropical areas because of the unique characteristics of polar biota. In addition, response to contaminants may be delayed, and hence longer exposure periods may be required in toxicity tests with polar species. In the present study, the sensitivity of 6 common subantarctic marine invertebrates to copper, zinc, and cadmium contaminants was determined. Large variations in sensitivities, both between species and between metals within species, were found. The bivalve Gaimardia trapesina and the copepod Harpacticus sp. were the most sensitive to copper, with 7-d median lethal concentration (LC50) values for both species ranging between 28 MUg/L and 62 MUg/L, whereas the copepod Tigriopus angulatus was the most tolerant of copper (7-d Cu LC50 1560 MUg/L). Sensitivity to zinc varied by approximately 1 order of magnitude between species (7-d LC50: 329-3057 MUg/L). Sensitivity to cadmium also varied considerably between species, with 7-d LC50 values ranging from 1612 MUg/L to >4383 MUg/L. The present study is the first to report the sensitivity of subantarctic marine invertebrate to metals, and contributes significantly to the understanding of latitudinal gradients in the sensitivity of biota to metals. Although sensitivity is highly variable between species, in a global comparison of copepod data, it appears that species from higher latitudes may be more sensitive to copper. Environ Toxicol Chem 2016;35:2245-2251. (c) 2016 SETAC. PMID- 26800987 TI - Neighborhood-Level and Spatial Characteristics Associated with Lay Naloxone Reversal Events and Opioid Overdose Deaths. AB - There were over 23,000 opioid overdose deaths in the USA in 2013, and opioid related mortality is increasing. Increased access to naloxone, particularly through community-based lay naloxone distribution, is a widely supported strategy to reduce opioid overdose mortality; however, little is known about the ecological and spatial patterns of the distribution and utilization of lay naloxone. This study aims to investigate the neighborhood-level correlates and spatial relationships of lay naloxone distribution and utilization and opioid overdose deaths. We determined the locations of lay naloxone distribution sites and the number of unintentional opioid overdose deaths and reported reversal events in San Francisco census tracts (n = 195) from 2010 to 2012. We used Wilcoxon rank-sum tests to compare census tract characteristics across tracts adjacent and not adjacent to distribution sites and multivariable negative binomial regression models to assess the association between census tract characteristics, including distance to the nearest site, and counts of opioid overdose deaths and naloxone reversal events. Three hundred forty-two opioid overdose deaths and 316 overdose reversals with valid location data were included in our analysis. Census tracts including or adjacent to a distribution site had higher income inequality, lower percentage black or African American residents, more drug arrests, higher population density, more overdose deaths, and more reversal events (all p < 0.05). In multivariable analysis, greater distance to the nearest distribution site (up to a distance of 4000 m) was associated with a lower count of Naloxone reversals [incidence rate ratio (IRR) = 0.51 per 500 m increase, 95% CI 0.39-0.67, p < 0.001] but was not significantly associated with opioid overdose deaths. These findings affirm that locating lay naloxone distribution sites in areas with high levels of substance use and overdose risk facilitates reversals of opioid overdoses in those immediate areas but suggests that alternative delivery methods may be necessary to reach individuals in other areas with less concentrated risk. PMID- 26800988 TI - A common miRNA160-based mechanism regulates ovary patterning, floral organ abscission and lamina outgrowth in tomato. AB - Plant microRNAs play vital roles in auxin signaling via the negative regulation of auxin response factors (ARFs). Studies have shown that targeting of ARF10/16/17 by miR160 is indispensable for various aspects of development, but its functions in the model crop tomato (Solanum lycopersicum) are unknown. Here we knocked down miR160 (sly-miR160) using a short tandem target mimic (STTM160), and investigated its roles in tomato development. Northern blot analysis showed that miR160 is abundant in developing ovaries. In line with this, its down regulation perturbed ovary patterning as indicated by the excessive elongation of the proximal ends of mutant ovaries and thinning of the placenta. Following fertilization, these morphological changes led to formation of elongated, pear shaped fruits reminiscent of those of the tomato ovate mutant. In addition, STTM160-expressing plants displayed abnormal floral organ abscission, and produced leaves, sepals and petals with diminished blades, indicating a requirement for sly-miR160 for these auxin-mediated processes. We found that sly miR160 depletion was always associated with the up-regulation of SlARF10A, SlARF10B and SlARF17, of which the expression of SlARF10A increased the most. Despite the sly-miR160 legitimate site of SlARF16A, its mRNA levels did not change in response to sly-miR160 down-regulation, suggesting that it may be regulated by a mechanism other than mRNA cleavage. SlARF10A and SlARF17 were previously suggested to function as inhibiting ARFs. We propose that by adjusting the expression of a group of ARF repressors, of which SlARF10A is a primary target, sly-miR160 regulates auxin-mediated ovary patterning as well as floral organ abscission and lateral organ lamina outgrowth. PMID- 26800989 TI - Predicting the structure and vibrational frequencies of ethylene using harmonic and anharmonic approaches at the Kohn-Sham complete basis set limit. AB - In this work, regular convergence patterns of the structural, harmonic, and VPT2 calculated anharmonic vibrational parameters of ethylene towards the Kohn-Sham complete basis set (KS CBS) limit are demonstrated for the first time. The performance of the VPT2 scheme implemented using density functional theory (DFT BLYP and DFT-B3LYP) in combination with two Pople basis sets (6-311++G** and 6 311++G(3df,2pd)), the polarization-consistent basis sets pc-n, aug-pc-n, and pcseg-n (n = 0, 1, 2, 3, 4), and the correlation-consistent basis sets cc-pVXZ and aug-cc-pVXZ (X = D, T, Q, 5, 6) was tested.The BLYP-calculated harmonic frequencies were found to be markedly closer than the B3LYP-calculated harmonic frequencies to the experimentally derived values, while the calculated anharmonic frequencies consistently underestimated the observed wavenumbers. The different basis set families gave very similar estimated values for the CBS parameters. The anharmonic frequencies calculated with B3LYP/aug-pc-3 were consistently significantly higher than those obtained with the pc-3 basis set; applying the aug-pcseg-n basis set family alleviated this problem. Utilization of B3LYP/aug pcseg-n basis sets instead of B3LYP/aug-cc-pVXZ, which is computationally less expensive, is suggested for medium-sized molecules. Harmonic BLYP/pc-2 calculations produced fairly accurate ethylene frequencies. Graphical Abstract In this study, the performance of the VPT2 scheme implemented using density functional theory (DFT-BLYP and DFT-B3LYP) in combination with the polarization consistent basis sets pc-n, aug-pc-n, and pcseg-n (n = 0, 1, 2, 3, 4), and the correlation-consistent basis sets cc-pVXZ and aug-cc-pVXZ (X = D, T, Q, 5, and 6) was tested. For the first time, we demonstrated regular convergence patterns of the structural, harmonic, and VPT2-calculated anharmonic vibrational parameters of ethylene towards the Kohn-Sham complete basis set (KS CBS) limit. PMID- 26800990 TI - Crisis, suicide and labour productivity losses in Spain. AB - OBJECTIVES: Suicide became the first cause of death between the ages of 15 and 44 in Spain in the year 2013. Moreover, the suicide rate in Spain went up by more than 9 % with respect to the previous year. This increase could be related to the serious economic recession that Spain has been experiencing in recent years. In this sense, there is a lack of evidence to help assess to what extent these suicides have a social cost in terms of losses in human capital. Firstly, this article examines the relationship between the variables related to the economic cycle and the suicide rates in the 17 Spanish regions. Secondly, an estimate is made of the losses in labour productivity owing to these suicides. METHODOLOGY: In this article, panel data models are used to consider different variables related to the economic cycle. Demographic variables and the suicide rates for regions across Spain from 2002 to 2013 also come into play. The present and future production costs owing to premature death from suicide are calculated using a human capital model. These costs are valued from the gross salary that an individual no longer receives in the future at the very moment he or she leaves the labour market. RESULTS: The results provide a strong indication that a decrease in economic growth and an increase in unemployment negatively affect suicide rates. Due to suicide, 38,038 potential years of working life were lost in 2013. This has an estimated cost of over 565 million euros. CONCLUSIONS: The economic crisis endured by Spain in recent years has played a role in the higher suicide rates one can observe from the data in official statistics. From a social perspective, suicide is a public health problem with far-reaching consequences. PMID- 26800991 TI - [Treatment of lateral ankle joint instability. Open or arthroscopic?]. AB - Chronic ankle joint instability often necessitates operative treatment. Operative treatment methods are classified into non-anatomical tenodesis, anatomical reconstruction and direct repair. In addition to open approaches, arthroscopic techniques are increasingly becoming established. This article describes the various operative treatment procedures, their advantages and disadvantages and in particular the arthroscopic feasibility. PMID- 26800992 TI - Real-Time PCR Quantification of Chloroplast DNA Supports DNA Barcoding of Plant Species. AB - Species identification from extracted DNA is sometimes needed for botanical samples. DNA quantification is required for an accurate and effective examination. If a quantitative assay provides unreliable estimates, a higher quantity of DNA than the estimated amount may be used in additional analyses to avoid failure to analyze samples from which extracting DNA is difficult. Compared with conventional methods, real-time quantitative PCR (qPCR) requires a low amount of DNA and enables quantification of dilute DNA solutions accurately. The aim of this study was to develop a qPCR assay for quantification of chloroplast DNA from taxonomically diverse plant species. An absolute quantification method was developed using primers targeting the ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL) gene using SYBR Green I-based qPCR. The calibration curve was generated using the PCR amplicon as the template. DNA extracts from representatives of 13 plant families common in Japan. This demonstrates that qPCR analysis is an effective method for quantification of DNA from plant samples. The results of qPCR assist in the decision-making will determine the success or failure of DNA analysis, indicating the possibility of optimization of the procedure for downstream reactions. PMID- 26800993 TI - Nitrogen-detected TROSY yields comparable sensitivity to proton-detected TROSY for non-deuterated, large proteins under physiological salt conditions. AB - Direct detection of the TROSY component of proton-attached (15)N nuclei ((15)N detected TROSY) yields high quality spectra with high field magnets, by taking advantage of the slow (15)N transverse relaxation. The slow transverse relaxation and narrow line width of the (15)N-detected TROSY resonances are expected to compensate for the inherently low (15)N sensitivity. However, the sensitivity of (15)N-detected TROSY in a previous report was one-order of magnitude lower than in the conventional (1)H-detected version. This could be due to the fact that the previous experiments were performed at low salt (0-50 mM), which is advantageous for (1)H-detected experiments. Here, we show that the sensitivity gap between (15)N and (1)H becomes marginal for a non-deuterated, large protein (tau c = 35 ns) at a physiological salt concentration (200 mM). This effect is due to the high salt tolerance of the (15)N-detected TROSY. Together with the previously reported benefits of the (15)N-detected TROSY, our results provide further support for the significance of this experiment for structural studies of macromolecules when using high field magnets near and above 1 GHz. PMID- 26800994 TI - The Biological Treatment of Paraphilic Disorders: an Updated Review. AB - Paraphilic disorders are characterized by atypical sexual interests, fantasies, and behaviors that are subjectively distressing to patients or pose a risk of harm to others. By their very nature, some paraphilic disorders may predispose an individual to commit sexual offenses. The biological treatment of paraphilic disorders, then, is of paramount importance for psychiatry and society at large. Three categories of pharmacologic agents commonly used to treat paraphilic disorders are selective serotonin reuptake inhibitors, synthetic steroidal analogs, and gonadotropin-releasing hormone analogs. Each medication uses a different mechanism of action and has different effects on the physiological and psychological features of paraphilic disorders. In general, these medications have limited high-quality research to support their use. Despite this, some authors have proposed treatment algorithms for individuals with paraphilic disorders of varying severity. These guidelines offer clinicians potentially useful, rational approaches to assessing treatment need in individuals with paraphilic disorders. Recent neuroimaging research suggests that functional magnetic resonance imaging may offer further promise in effectively assessing paraphilic disorders to help direct treatment options. PMID- 26800995 TI - Prevention of Post-Traumatic Stress Disorder After Trauma: Current Evidence and Future Directions. AB - Post-traumatic stress disorder (PTSD) is a frequent, tenacious, and disabling consequence of traumatic events. The disorder's identifiable onset and early symptoms provide opportunities for early detection and prevention. Empirical findings and theoretical models have outlined specific risk factors and pathogenic processes leading to PTSD. Controlled studies have shown that theory driven preventive interventions, such as cognitive behavioral therapy (CBT), or stress hormone-targeted pharmacological interventions, are efficacious in selected samples of survivors. However, the effectiveness of early clinical interventions remains unknown, and results obtained in aggregates (large groups) overlook individual heterogeneity in PTSD pathogenesis. We review current evidence of PTSD prevention and outline the need to improve the disorder's early detection and intervention in individual-specific paths to chronic PTSD. PMID- 26800996 TI - Co-culture with intestinal epithelial organoids allows efficient expansion and motility analysis of intraepithelial lymphocytes. AB - BACKGROUND: Intraepithelial lymphocytes (IELs) in the intestine play important roles in the regulation of local immune responses. Although their functions have been studied in a variety of animal experiments, in vitro studies on spatiotemporal behaviors of IELs and their interaction with intestinal epithelial cells (IECs) have been hampered due to the lack of a suitable culture system. In this study, we aimed at developing a novel co-culture system of IELs with IECs to investigate dynamic interaction between these two populations of cells in vitro. METHODS: We optimized experimental conditions under which murine IELs can be efficiently maintained with IECs cultured as three-dimensional organoids. We then tested the effect of IL-2, IL-7, and IL-15 on the maintenance of IELs in this co culture system. By time-lapse imaging, we also examined the dynamic behaviors of IELs. RESULTS: IELs can be expanded with epithelial organoids in the presence of IL-2, IL-7, and IL-15. IELs were efficiently maintained within and outside of organoids showing a ~four-fold increase in both alphabetaT and gammadeltaT IELs for a period of 2 weeks. Four-dimensional fluorescent imaging revealed an active, multi-directional movement of IELs along the basolateral surface of IECs, and also their inward or outward migration relative to organoid structures. Cell tracking analysis showed that alphabetaT and gammadeltaT IELs shared indistinguishable features with regard to their dynamics. CONCLUSIONS: This novel co-culture method could serve as a unique tool to investigate the motility dynamics of IELs and their temporal and spatial interaction with IECs in vitro. PMID- 26800998 TI - Unusual combination: Ebstein's anomaly and hypertrophic obstructive cardiomyopathy. PMID- 26800997 TI - Effect of ramosetron in female patients with irritable bowel syndrome with diarrhea: a phase III long-term study. AB - BACKGROUND: The long-term safety of administration of ramosetron in female patients with irritable bowel syndrome with diarrhea (IBS-D) is unknown. The aim of this study was to assess the long-term safety, tolerability, and outcomes with the use of ramosetron in female patients with IBS-D. METHODS: This was a phase III, open-label, uncontrolled, long-term safety trial of the treatment of female Japanese patients with IBS-D, diagnosed according to the Rome III criteria. A total of 151 patients were given 2.5 MUg of ramosetron for 4 weeks, and responders continued the same dose for another 48 weeks. Non-responders at 4 weeks were given 5 MUg of ramosetron for 48 weeks. At the end of week 52, 106 patients receiving 2.5 MUg and 17 patients receiving 5 MUg had completed the study. Safety and efficacy including symptoms and quality of life (QOL) were evaluated. RESULTS: Concerning safety, no serious adverse event related to ramosetron, specifically ischemic colitis, was observed in patients with either dose of ramosetron. However, constipation occurred in 19.7 % of patients given 2.5 MUg and 10.5 % of patients given 5 MUg of ramosetron. Ramosetron-treated patients showed high rates of global improvement. Stool consistency, abdominal pain and discomfort, and IBS-QOL were also improved at the last evaluation point. CONCLUSIONS: The results provide evidence of the long-term safety and efficacy of treatment with 2.5 and 5 MUg of ramosetron in female patients with IBS-D. Clinicians should be aware that one-fifth of women with IBS-D receiving ramosetron may suffer from constipation during treatment (ClinicalTrials.gov ID: NCT01736423). PMID- 26800999 TI - Diagnostic performance of MRI for prediction of candidates for local excision of rectal cancer (ypT0-1N0) after neoadjuvant chemoradiation therapy. AB - PURPOSE: To evaluate the diagnostic performance of rectal MRI in predicting candidates for local excision (LE; ypT0-1N0) after neoadjuvant chemoradiation therapy (CRT) in patients with rectal cancer. MATERIALS AND METHODS: The institutional review board approved our retrospective study and waived informed consent. Inclusion criteria were as follows: patients with pathologically confirmed mid to lower rectal cancer (cT3NxM0 before neoadjuvant CRT) who underwent neoadjuvant CRT and had MRI performed at 3T before and after neoadjuvant CRT. A total of 168 patients met the study criteria between 2011 and 2012. Two observers independently assessed tumor and nodal stages on MR images obtained after neoadjuvant CRT. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for identifying a candidate for LE (ypT0-1N0) were calculated. Interobserver agreement was assessed with kappa value. Predictive factors for ypT0-1N0 were evaluated by logistic regression models. RESULTS: MRI had relatively high accuracy, specificity, and NPV (85.9%, 93.8%, and 88.9% for observer 1 and 85.3%, 96.1%, and 86.6% for observer 2), moderate PPV (71.4% and 76.2%), and relatively low sensitivity (57.1% and 45.7%) for predicting ypT0-1N0. The interobserver agreement was fair (kappa value = 0.593). Carcinoembryonic antigen levels after neoadjuvant CRT and the maximal extramural depth of tumor spread were significant predictors of ypT0 1N0 (P = 0.037 and 0.017, respectively). CONCLUSION: MRI after neoadjuvant CRT can predict a candidate for LE (ypT0-1N0) after neoadjuvant CRT with moderate PPV and relatively high NPV. J. Magn. Reson. Imaging 2016;44:471-477. PMID- 26801000 TI - The consequences of poaching and anthropogenic change for forest elephants. AB - Poaching has devastated forest elephant populations (Loxodonta cyclotis), and their habitat is dramatically changing. The long-term effects of poaching and other anthropogenic threats have been well studied in savannah elephants (Loxodonta africana), but the impacts of these changes for Central Africa's forest elephants have not been discussed. We examined potential repercussions of these threats and the related consequences for forest elephants in Central Africa by summarizing the lessons learned from savannah elephants and small forest elephant populations in West Africa. Forest elephant social organization is less known than the social organization of savannah elephants, but the close evolutionary history of these species suggests that they will respond to anthropogenic threats in broadly similar ways. The loss of older, experienced individuals in an elephant population disrupts ecological, social, and population parameters. Severe reduction of elephant abundance within Central Africa's forests can alter plant communities and ecosystem functions. Poaching, habitat alterations, and human population increase are probably compressing forest elephants into protected areas and increasing human-elephant conflict, which negatively affects their conservation. We encourage conservationists to look beyond documenting forest elephant population decline and address the causes of these declines when developing conversation strategies. We suggest assessing the effectiveness of the existing protected-area networks for landscape connectivity in light of current industrial and infrastructure development. Longitudinal assessments of the effects of landscape changes on forest elephant sociality and behavior are also needed. Finally, lessons learned from West African elephant population loss and habitat fragmentation should be used to inform strategies for land-use planning and managing human-elephant interactions. PMID- 26801001 TI - Predictors of Uncontrolled Blood Pressure in Treated Hypertensive Individuals: First Population-Based Study in Lebanon. AB - Arterial hypertension is a leading risk factor for cardiovascular disease and stroke. This study aimed to assess the predictors of uncontrolled systolic and diastolic blood pressure (BP) in Lebanon among treated hypertensive individuals. The authors included 562 participants 40 years and older. The potential predictors included sociodemographic characteristics, self-reported health information, and medication adherence. Prevalence of uncontrolled systolic and diastolic BP reached 43.1% and 24.9%, respectively. Independent predictors of uncontrolled systolic BP were older age, male sex, and low and medium medication adherence level. Predictors of uncontrolled diastolic BP were younger age, obesity, and low medication adherence level. Married individuals and patients taking statins had better diastolic BP control. Uncontrolled BP is a major public health problem in Lebanon. The authors identified low adherence as a major modifiable risk factor for systolic and diastolic BP control and obesity as a major modifiable risk factor for diastolic BP control. PMID- 26801003 TI - Zebrafish Leucocyte tyrosine kinase controls iridophore establishment, proliferation and survival. AB - The zebrafish striped pattern results from the interplay among three pigment cell types; black melanophores, yellow xanthophores and silvery iridophores, making it a valuable model to study pattern formation in vivo. It has been suggested that iridophore proliferation, dispersal and cell shape transitions play an important role during stripe formation; however, the underlying molecular mechanisms remain poorly understood. Using gain- and loss-of-function alleles of leucocyte tyrosine kinase (ltk) and a pharmacological inhibitor approach, we show that Ltk specifically regulates iridophore establishment, proliferation and survival. Mutants in shady/ltk lack iridophores and display an abnormal body stripe pattern. Moonstone mutants, ltk(mne) , display ectopic iridophores, suggesting hyperactivity of the mutant Ltk. The dominant ltk(mne) allele carries a missense mutation in a conserved position of the kinase domain that highly correlates with neuroblastomas in mammals. Chimeric analysis suggests a novel physiological role of Ltk in the regulation of iridophore proliferation by homotypic competition. PMID- 26801004 TI - Congenital reticular ichthyosiform erythroderma. PMID- 26801005 TI - Hyoid surgery alone for obstructive sleep apnea: A systematic review and meta analysis. AB - OBJECTIVES/HYPOTHESIS: The primary objective was to determine if sleep study variables (e.g., apnea-hypopnea index [AHI] and lowest oxygen saturation) and quantitative sleepiness data improve following isolated hyoid surgery for obstructive sleep apnea (OSA). STUDY DESIGN: Systematic review and meta-analysis. METHODS: Nine databases, including PubMed, were searched through September 5, 2015. RESULTS: Four hundred ninety-eight studies were screened, 64 were reviewed, and nine studies met inclusion criteria. A total of 101 patients were identified who underwent hyoid surgery alone for treatment of OSA. Subanalyses were performed for: 1) type of surgery, 2) primary versus secondary hyoid surgery, 3) positional versus nonpositional OSA, 4) age, and 5) body mass index. In patients undergoing isolated hyoid surgery, the AHI decreased from a mean +/- standard deviation of 37.3 +/- 21.1 (95% confidence interval [CI]: 33.1, 41.5) to 23.0 +/- 18.6 (95% CI: 19.3, 26.7) events/hour, which correspond to a 38.3% reduction (P < .0001). AHI reduced by 38.3% for hyoid myotomy with suspension, by 50.7% for hyothyroidopexy, and by 7.1% for hyoid expansion. The Epworth Sleepiness Scale decreased by 3.2 points from 10.3 +/- 4.9 (95% CI: 8.8, 11.8) to 7.1 +/- 4.2 (95% CI: 5.8, 8.4; P = .0027). CONCLUSIONS: Isolated hyoid surgery has reduced OSA severity and improved sleepiness in adults. Hyothyroidopexy provided a 50.7% reduction in AHI, followed by hyoid myotomy with suspension (38.3% reduction in AHI) and hyoid expansion (7.1% reduction in AHI). The current literature lacks high-quality evidence with regard to hyoid surgery, and additional studies are needed to further elucidate the effect of hyoid surgery in OSA. LEVEL OF EVIDENCE: NA Laryngoscope, 126:1702-1708, 2016. PMID- 26801006 TI - Cytological findings of odontogenic myxofibroma: A diagnostic dilemma. AB - Odontogenic myxofibroma represents a rare slow-growing benign neoplasm, which usually occurs in the second and third decades of life and rarely in children or adults over 50 years of age. Myxomas in general represent from 2.3% to 17.7% of all odontogenic tumors, and myxofibromas represent a small number of all myxomas. Limited evidence is present in literature regarding the cytological diagnosis of odontogenic myxoma/myxofibroma. We hereby report the cytomorphological features of a histologically confirmed case of odontogenic myxofibroma and the pitfalls of the cytological diagnosis. A painless jaw swelling in a young boy was aspirated. Scanty mucoid material was obtained. Cytology Smears were moderately cellular and showed a population comprising predominantly of singly scattered plump to fusiform cells with bipolar cytoplasmic processes showing mild to moderate atypia embedded within dense myxoid matrix and another population of cells arranged in clusters. Case was interpreted as low grade mesenchymal tumor. Subsequent biopsy confirmed it as odontogenic myxofibroma arising in a odontogenic keratocyst. Precise interpretation of intraosseous jaw lesions FNAC may not always be possible, but an attempt should be made to broadly classify the lesion as an inflammatory lesion, cystic lesion, giant cell lesion, fibro-osseous lesion or as an odontogenic tumor. If dual population of odontogenic epithelium and mesenchymal cells embedded in myxoid matrix are identified in such aspirates, a possibility of myxoid odontogenic tumor may be suggested. Triple correlation of cytological, clinical and radiological findings can guide the surgeon for taking appropriate therapeutic decisions. PMID- 26801008 TI - In vitro antiviral activity of Lactobacillus casei and Bifidobacterium adolescentis against rotavirus infection monitored by NSP4 protein production. AB - AIMS: The aim of this study was to determine the antiviral activity of four probiotic metabolites (Lactobacillus and Bifidobacetrium species) against rotavirus in vitro infection monitored by the NSP4 protein production and Ca(2+) release. METHODS AND RESULTS: The antiviral effect of the metabolites was performed due a comparison between a blocking model and an intracelullar model on MA104 cells, with the response of NSP4 production and Ca(2+) liberation measured by flow cytometry. Significant results were obtained with the metabolites of Lactobacillus casei, and Bifidobacterium adolescentis in the reduction of the protein production (P = 0.04 and P = 0.014) and Ca(2+) liberation (P = 0.094 and P = 0.020) in the intracellular model, which suggests a successful antiviral activity against RV infection. CONCLUSIONS: This study demonstrates that probiotic metabolites were able to interfere with the final amount of intracellular NSP4 protein and a successful Ca(2+) regulation, which suggests a new approach to the mechanism exerted by probiotics against the rotavirus infection. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel anti-rotaviral effect exerted by probiotic metabolites monitored by the NSP4 protein during the RV in vitro infection and the effect on the Ca(2+) release is reported; suggesting a reduction on the impact of the infection by decreasing the damage of the cells preventing the electrolyte loss. PMID- 26801009 TI - Increased expression of CXCR3 and its ligands in patients with vitiligo and CXCL10 as a potential clinical marker for vitiligo. AB - BACKGROUND: Vitiligo is a skin disorder characterized by loss of melanocytes from the epidermis. A recent study reported that CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo, but there is very limited clinical data regarding this issue and little is known about the dynamic changes or correlations with disease severity of these chemokines throughout the disease course. OBJECTIVES: To present clinical data that supports and identifies the pathway of CXCR3 and its ligands in T lymphocytic cell recruitment in vitiligo. METHODS: Cytometric bead array, flow cytometry, quantitative real-time polymerase chain reaction and immunohistology were used to examine their systemic and local expression in 80 patients with vitiligo and 40 controls. RESULTS: We showed that serum CXCL9 and CXCL10 were significantly elevated in patients with vitiligo and were higher in patients in progressive stages than in stable stages. The relative expression of CXCR3 mRNA in peripheral blood mononuclear cells was higher in vitiligo. There were higher percentages of both circulating CXCR3(+) CD4(+) and CXCR3(+) CD8(+) T cells in patients with progressive vitiligo compared with controls, while only the expression of CXCR3(+) CD8(+) T cells increased in patients with stable vitiligo. Histological findings also demonstrated an abundance of CXCR3(+) cells within vitiligo lesions. Furthermore, serum CXCL10 levels were associated with Vitiligo Area Scoring Index scores of patients with progressive vitiligo and were reduced after successful treatment. CONCLUSIONS: The CXCL10/CXCR3 axis mediates T-cell recruitment into the skin in progressive vitiligo. Blocking this chemotactic mechanism may present a new form of therapy. Serum CXCL10 may be a novel biomarker in monitoring disease activity and guiding treatment of progressive vitiligo. PMID- 26801007 TI - Fusarium oxysporum mediates systems metabolic reprogramming of chickpea roots as revealed by a combination of proteomics and metabolomics. AB - Molecular changes elicited by plants in response to fungal attack and how this affects plant-pathogen interaction, including susceptibility or resistance, remain elusive. We studied the dynamics in root metabolism during compatible and incompatible interactions between chickpea and Fusarium oxysporum f. sp. ciceri (Foc), using quantitative label-free proteomics and NMR-based metabolomics. Results demonstrated differential expression of proteins and metabolites upon Foc inoculations in the resistant plants compared with the susceptible ones. Additionally, expression analysis of candidate genes supported the proteomic and metabolic variations in the chickpea roots upon Foc inoculation. In particular, we found that the resistant plants revealed significant increase in the carbon and nitrogen metabolism; generation of reactive oxygen species (ROS), lignification and phytoalexins. The levels of some of the pathogenesis-related proteins were significantly higher upon Foc inoculation in the resistant plant. Interestingly, results also exhibited the crucial role of altered Yang cycle, which contributed in different methylation reactions and unfolded protein response in the chickpea roots against Foc. Overall, the observed modulations in the metabolic flux as outcome of several orchestrated molecular events are determinant of plant's role in chickpea-Foc interactions. PMID- 26801011 TI - Perspective: Mechanochemistry of biological and synthetic molecules. AB - Coupling of mechanical forces and chemical transformations is central to the biophysics of molecular machines, polymer chemistry, fracture mechanics, tribology, and other disciplines. As a consequence, the same physical principles and theoretical models should be applicable in all of those fields; in fact, similar models have been invoked (and often repeatedly reinvented) to describe, for example, cell adhesion, dry and wet friction, propagation of cracks, and action of molecular motors. This perspective offers a unified view of these phenomena, described in terms of chemical kinetics with rates of elementary steps that are force dependent. The central question is then to describe how the rate of a chemical transformation (and its other measurable properties such as the transition path) depends on the applied force. I will describe physical models used to answer this question and compare them with experimental measurements, which employ single-molecule force spectroscopy and which become increasingly common. Multidimensionality of the underlying molecular energy landscapes and the ensuing frequent misalignment between chemical and mechanical coordinates result in a number of distinct scenarios, each showing a nontrivial force dependence of the reaction rate. I will discuss these scenarios, their commonness (or its lack), and the prospects for their experimental validation. Finally, I will discuss open issues in the field. PMID- 26801012 TI - Communication: An effective linear-scaling atomic-orbital reformulation of the random-phase approximation using a contracted double-Laplace transformation. AB - An atomic-orbital (AO) reformulation of the random-phase approximation (RPA) correlation energy is presented allowing to reduce the steep computational scaling to linear, so that large systems can be studied on simple desktop computers with fully numerically controlled accuracy. Our AO-RPA formulation introduces a contracted double-Laplace transform and employs the overlap-metric resolution-of-the-identity. First timings of our pilot code illustrate the reduced scaling with systems comprising up to 1262 atoms and 10 090 basis functions. . PMID- 26801010 TI - Cortical hierarchy governs rat claustrocortical circuit organization. AB - The claustrum is a telencephalic gray matter structure with various proposed functions, including sensory integration and attentional allocation. Underlying these concepts is the reciprocal connectivity of the claustrum with most, if not all, areas of the cortex. What remains to be elucidated to inform functional hypotheses further is whether a pattern exists in the strength of connectivity between a given cortical area and the claustrum. To this end, we performed a series of retrograde neuronal tract tracer injections into rat cortical areas along the cortical processing hierarchy, from primary sensory and motor to frontal cortices. We observed that the number of claustrocortical projections increased as a function of processing hierarchy; claustrum neurons projecting to primary sensory cortices were scant and restricted in distribution across the claustrum, whereas neurons projecting to the cingulate cortex were densely packed and more evenly distributed throughout the claustrum. This connectivity pattern suggests that the claustrum may preferentially subserve executive functions orchestrated by the cingulate cortex. J. Comp. Neurol. 525:1347-1362, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26801013 TI - Communication: Accurate higher-order van der Waals coefficients between molecules from a model dynamic multipole polarizability. AB - Due to the absence of the long-range van der Waals (vdW) interaction, conventional density functional theory (DFT) often fails in the description of molecular complexes and solids. In recent years, considerable progress has been made in the development of the vdW correction. However, the vdW correction based on the leading-order coefficient C6 alone can only achieve limited accuracy, while accurate modeling of higher-order coefficients remains a formidable task, due to the strong non-additivity effect. Here, we apply a model dynamic multipole polarizability within a modified single-frequency approximation to calculate C8 and C10 between small molecules. We find that the higher-order vdW coefficients from this model can achieve remarkable accuracy, with mean absolute relative deviations of 5% for C8 and 7% for C10. Inclusion of accurate higher-order contributions in the vdW correction will effectively enhance the predictive power of DFT in condensed matter physics and quantum chemistry. PMID- 26801014 TI - Anisotropy induced Kondo splitting in a mechanically stretched molecular junction: A first-principles based study. AB - The magnetic anisotropy and Kondo phenomena in a mechanically stretched magnetic molecular junction are investigated by combining the density functional theory (DFT) and hierarchical equations of motion (HEOM) approach. The system is comprised of a magnetic complex Co(tpy-SH)2 sandwiched between adjacent gold electrodes, which is mechanically stretched in experiments done by Parks et al. [Science 328, 1370 (2010)]. The electronic structure and mechanical property of the stretched system are investigated via the DFT calculations. The HEOM approach is then employed to characterize the Kondo resonance features, based on the Anderson impurity model parameterized from the DFT results. It is confirmed that the ground state prefers the S = 1 local spin state. The structural properties, the magnetic anisotropy, and corresponding Kondo peak splitting in the axial stretching process are systematically evaluated. The results reveal that the strong electron correlations and the local magnetic properties of the molecule magnet are very sensitive to structural distortion. This work demonstrates that the combined DFT+HEOM approach could be useful in understanding and designing mechanically controlled molecular junctions. PMID- 26801015 TI - Speeding up equation of motion coupled cluster theory with the chain of spheres approximation. AB - In the present paper, the chain of spheres exchange (COSX) approximation is applied to the highest scaling terms in the equation of motion (EOM) coupled cluster equations with single and double excitations, in particular, the terms involving integrals with four virtual labels. It is found that even the acceleration of this single term yields significant computational gains without compromising the desired accuracy of the method. For an excitation energy calculation on a cluster of five water molecules using 585 basis functions, the four virtual term is 9.4 times faster using COSX with a loose grid than using the canonical implementation, which yields a 2.6 fold acceleration for the whole of the EOM calculation. For electron attachment calculations, the four virtual term is 15 times and the total EOM calculation is 10 times faster than the canonical calculation for the same system. The accuracy of the new method was tested using Thiel's test set for excited states using the same settings and the maximum absolute deviation over the whole test set was found to be 12.945 cm(-1) (59 MUHartree) for excitation energies and 6.799 cm(-1) (31 MUHartree) for electron attachments. Using MP2 amplitudes for the ground state in combination with the parallel evaluation of the full EOM equations in the manner discussed in this paper enabled us to perform calculations for large systems. Electron affinity values for the two lowest states of a Zn protoporphyrine model compound (224 correlated electrons and 1120 basis functions) were obtained in 3 days 19 h using 4 cores of a Xeon E5-2670 processor allocating 10 GB memory per core. Calculating the lowest two excitation energies for trans-retinal (114 correlated electrons and 539 basis functions) took 1 day 21 h using eight cores of the same processor and identical memory allocation per core. PMID- 26801016 TI - Quasi-degenerate perturbation theory using matrix product states. AB - In this work, we generalize the recently proposed matrix product state perturbation theory (MPSPT) for calculating energies of excited states using quasi-degenerate (QD) perturbation theory. Our formulation uses the Kirtman Certain-Hirschfelder canonical Van Vleck perturbation theory, which gives Hermitian effective Hamiltonians at each order, and also allows one to make use of Wigner's 2n + 1 rule. Further, our formulation satisfies Granovsky's requirement of model space invariance which is important for obtaining smooth potential energy curves. Thus, when we use MPSPT with the Dyall Hamiltonian, we obtain a model space invariant version of quasi-degenerate n-electron valence state perturbation theory (NEVPT), a property that the usual formulation of QD NEVPT2 based on a multipartitioning technique lacked. We use our method on the benchmark problems of bond breaking of LiF which shows ionic to covalent curve crossing and the twist around the double bond of ethylene where significant valence-Rydberg mixing occurs in the excited states. In accordance with our previous work, we find that multi-reference linearized coupled cluster theory is more accurate than other multi-reference theories of similar cost. PMID- 26801017 TI - Redesign of the DFT/MRCI Hamiltonian. AB - The combined density functional theory and multireference configuration interaction (DFT/MRCI) method of Grimme and Waletzke [J. Chem. Phys. 111, 5645 (1999)] is a well-established semi-empirical quantum chemical method for efficiently computing excited-state properties of organic molecules. As it turns out, the method fails to treat bi-chromophores owing to the strong dependence of the parameters on the excitation class. In this work, we present an alternative form of correcting the matrix elements of a MRCI Hamiltonian which is built from a Kohn-Sham set of orbitals. It is based on the idea of constructing individual energy shifts for each of the state functions of a configuration. The new parameterization is spin-invariant and incorporates less empirism compared to the original formulation. By utilizing damping techniques together with an algorithm of selecting important configurations for treating static electron correlation, the high computational efficiency has been preserved. The robustness of the original and redesigned Hamiltonians has been tested on experimentally known vertical excitation energies of organic molecules yielding similar statistics for the two parameterizations. Besides that, our new formulation is free from artificially low-lying doubly excited states, producing qualitatively correct and consistent results for excimers. The way of modifying matrix elements of the MRCI Hamiltonian presented here shall be considered as default choice when investigating photophysical processes of bi-chromophoric systems such as singlet fission or triplet-triplet upconversion. PMID- 26801018 TI - Wetting transitions on patterned surfaces with diffuse interaction potentials embedded in a Young-Laplace formulation. AB - The Minimum Energy Paths (MEPs) of wetting transitions on pillared surfaces are computed with the Young-Laplace equation, augmented with a pressure term that accounts for liquid-solid interactions. The interactions are smoothed over a short range from the solid phase, therefore facilitating the numerical solution of problems concerning wetting on complex surface patterns. The patterns may include abrupt geometric features, e.g., arrays of rectangular pillars, where the application of the unmodified Young-Laplace is not practical. The MEPs are obtained by coupling the augmented Young-Laplace with the modified string method from which the energy barriers of wetting transitions are eventually extracted. We demonstrate the method on a wetting transition that is associated with the breakdown of superhydrophobic behavior, i.e., the transition from the Cassie Baxter state to the Wenzel state, taking place on a superhydrophobic pillared surface. The computed energy barriers quantify the resistance of the system to these transitions and therefore, they can be used to evaluate superhydrophobic performance or provide guidelines for optimal pattern design. PMID- 26801019 TI - First passage times in homogeneous nucleation: Dependence on the total number of particles. AB - Motivated by nucleation and molecular aggregation in physical, chemical, and biological settings, we present an extension to a thorough analysis of the stochastic self-assembly of a fixed number of identical particles in a finite volume. We study the statistics of times required for maximal clusters to be completed, starting from a pure-monomeric particle configuration. For finite volumes, we extend previous analytical approaches to the case of arbitrary size dependent aggregation and fragmentation kinetic rates. For larger volumes, we develop a scaling framework to study the first assembly time behavior as a function of the total quantity of particles. We find that the mean time to first completion of a maximum-sized cluster may have a surprisingly weak dependence on the total number of particles. We highlight how higher statistics (variance, distribution) of the first passage time may nevertheless help to infer key parameters, such as the size of the maximum cluster. Finally, we present a framework to quantify formation of macroscopic sized clusters, which are (asymptotically) very unlikely and occur as a large deviation phenomenon from the mean-field limit. We argue that this framework is suitable to describe phase transition phenomena, as inherent infrequent stochastic processes, in contrast to classical nucleation theory. PMID- 26801021 TI - Local conditions for the Pauli potential in order to yield self-consistent electron densities exhibiting proper atomic shell structure. AB - The local conditions for the Pauli potential that are necessary in order to yield self-consistent electron densities from orbital-free calculations are investigated for approximations that are expressed with the help of a local position variable. It is shown that those local conditions also apply when the Pauli potential is given in terms of the electron density. An explicit formula for the Ne atom is given, preserving the local conditions during the iterative procedure. The resulting orbital-free electron density exhibits proper shell structure behavior and is in close agreement with the Kohn-Sham electron density. This study demonstrates that it is possible to obtain self-consistent orbital free electron densities with proper atomic shell structure from simple one-point approximations for the Pauli potential at local density level. PMID- 26801020 TI - Locally weighted histogram analysis and stochastic solution for large-scale multi state free energy estimation. AB - The weighted histogram analysis method (WHAM) including its binless extension has been developed independently in several different contexts, and widely used in chemistry, physics, and statistics, for computing free energies and expectations from multiple ensembles. However, this method, while statistically efficient, is computationally costly or even infeasible when a large number, hundreds or more, of distributions are studied. We develop a locally WHAM (local WHAM) from the perspective of simulations of simulations (SOS), using generalized serial tempering (GST) to resample simulated data from multiple ensembles. The local WHAM equations based on one jump attempt per GST cycle can be solved by optimization algorithms orders of magnitude faster than standard implementations of global WHAM, but yield similarly accurate estimates of free energies to global WHAM estimates. Moreover, we propose an adaptive SOS procedure for solving local WHAM equations stochastically when multiple jump attempts are performed per GST cycle. Such a stochastic procedure can lead to more accurate estimates of equilibrium distributions than local WHAM with one jump attempt per cycle. The proposed methods are broadly applicable when the original data to be "WHAMMED" are obtained properly by any sampling algorithm including serial tempering and parallel tempering (replica exchange). To illustrate the methods, we estimated absolute binding free energies and binding energy distributions using the binding energy distribution analysis method from one and two dimensional replica exchange molecular dynamics simulations for the beta-cyclodextrin-heptanoate host-guest system. In addition to the computational advantage of handling large datasets, our two dimensional WHAM analysis also demonstrates that accurate results similar to those from well-converged data can be obtained from simulations for which sampling is limited and not fully equilibrated. PMID- 26801022 TI - GW and Bethe-Salpeter study of small water clusters. AB - We study within the GW and Bethe-Salpeter many-body perturbation theories the electronic and optical properties of small (H2O)n water clusters (n = 1-6). Comparison with high-level CCSD(T) Coupled-Cluster at the Single Double (Triple) levels and ADC(3) Green's function third order algebraic diagrammatic construction calculations indicates that the standard non-self-consistent G0W0@PBE or G0W0@PBE0 approaches significantly underestimate the ionization energy by about 1.1 eV and 0.5 eV, respectively. Consequently, the related Bethe Salpeter lowest optical excitations are found to be located much too low in energy when building transitions from a non-self-consistent G0W0 description of the quasiparticle spectrum. Simple self-consistent schemes, with update of the eigenvalues only, are shown to provide a weak dependence on the Kohn-Sham starting point and a much better agreement with reference calculations. The present findings rationalize the theory to experiment possible discrepancies observed in previous G0W0 and Bethe-Salpeter studies of bulk water. The increase of the optical gap with increasing cluster size is consistent with the evolution from gas to dense ice or water phases and results from an enhanced screening of the electron-hole interaction. PMID- 26801023 TI - A whole-path importance-sampling scheme for Feynman path integral calculations of absolute partition functions and free energies. AB - Using Feynman path integrals, a molecular partition function can be written as a double integral with the inner integral involving all closed paths centered at a given molecular configuration, and the outer integral involving all possible molecular configurations. In previous work employing Monte Carlo methods to evaluate such partition functions, we presented schemes for importance sampling and stratification in the molecular configurations that constitute the path centroids, but we relied on free-particle paths for sampling the path integrals. At low temperatures, the path sampling is expensive because the paths can travel far from the centroid configuration. We now present a scheme for importance sampling of whole Feynman paths based on harmonic information from an instantaneous normal mode calculation at the centroid configuration, which we refer to as harmonically guided whole-path importance sampling (WPIS). We obtain paths conforming to our chosen importance function by rejection sampling from a distribution of free-particle paths. Sample calculations on CH4 demonstrate that at a temperature of 200 K, about 99.9% of the free-particle paths can be rejected without integration, and at 300 K, about 98% can be rejected. We also show that it is typically possible to reduce the overhead associated with the WPIS scheme by sampling the paths using a significantly lower-order path discretization than that which is needed to converge the partition function. PMID- 26801024 TI - Dispersion dipoles for coupled Drude oscillators. AB - We present the dispersion-induced dipole moments of coupled Drude oscillators obtained from two approaches. The first approach evaluates the dipole moment using the second-order Rayleigh-Schrodinger perturbation theory wave function allowing for dipole-dipole and dipole-quadrupole coupling. The second approach, based on response theory, employs an integral of the dipole-dipole polarizability of one oscillator and the dipole-dipole-quadrupole hyperpolarizability of the other oscillator over imaginary frequencies. The resulting dispersion dipoles exhibit an R(-7) dependence on the separation between the two oscillators and are connected to the leading-order C6/R(6) dispersion energy through the electrostatic Hellmann-Feynman theorem. PMID- 26801025 TI - Broadband cross-polarization-based heteronuclear dipolar recoupling for structural and dynamic NMR studies of rigid and soft solids. AB - Dipolar recoupling is an essential part of current solid-state NMR methodology for probing atomic-resolution structure and dynamics in solids and soft matter. Recently described magic-echo amplitude- and phase-modulated cross-polarization heteronuclear recoupling strategy aims at efficient and robust recoupling in the entire range of coupling constants both in rigid and highly dynamic molecules. In the present study, the properties of this recoupling technique are investigated by theoretical analysis, spin-dynamics simulation, and experimentally. The resonance conditions and the efficiency of suppressing the rf field errors are examined and compared to those for other recoupling sequences based on similar principles. The experimental data obtained in a variety of rigid and soft solids illustrate the scope of the method and corroborate the results of analytical and numerical calculations. The technique benefits from the dipolar resolution over a wider range of coupling constants compared to that in other state-of-the-art methods and thus is advantageous in studies of complex solids with a broad range of dynamic processes and molecular mobility degrees. PMID- 26801027 TI - A fingerprint based metric for measuring similarities of crystalline structures. AB - Measuring similarities/dissimilarities between atomic structures is important for the exploration of potential energy landscapes. However, the cell vectors together with the coordinates of the atoms, which are generally used to describe periodic systems, are quantities not directly suitable as fingerprints to distinguish structures. Based on a characterization of the local environment of all atoms in a cell, we introduce crystal fingerprints that can be calculated easily and define configurational distances between crystalline structures that satisfy the mathematical properties of a metric. This distance between two configurations is a measure of their similarity/dissimilarity and it allows in particular to distinguish structures. The new method can be a useful tool within various energy landscape exploration schemes, such as minima hopping, random search, swarm intelligence algorithms, and high-throughput screenings. PMID- 26801026 TI - Constant-time 2D and 3D through-bond correlation NMR spectroscopy of solids under 60 kHz MAS. AB - Establishing connectivity and proximity of nuclei is an important step in elucidating the structure and dynamics of molecules in solids using magic angle spinning (MAS) NMR spectroscopy. Although recent studies have successfully demonstrated the feasibility of proton-detected multidimensional solid-state NMR experiments under ultrafast-MAS frequencies and obtaining high-resolution spectral lines of protons, assignment of proton resonances is a major challenge. In this study, we first re-visit and demonstrate the feasibility of 2D constant time uniform-sign cross-peak correlation (CTUC-COSY) NMR experiment on rigid solids under ultrafast-MAS conditions, where the sensitivity of the experiment is enhanced by the reduced spin-spin relaxation rate and the use of low radio frequency power for heteronuclear decoupling during the evolution intervals of the pulse sequence. In addition, we experimentally demonstrate the performance of a proton-detected pulse sequence to obtain a 3D (1)H/(13)C/(1)H chemical shift correlation spectrum by incorporating an additional cross-polarization period in the CTUC-COSY pulse sequence to enable proton chemical shift evolution and proton detection in the incrementable t1 and t3 periods, respectively. In addition to through-space and through-bond (13)C/(1)H and (13)C/(13)C chemical shift correlations, the 3D (1)H/(13)C/(1)H experiment also provides a COSY-type (1)H/(1)H chemical shift correlation spectrum, where only the chemical shifts of those protons, which are bonded to two neighboring carbons, are correlated. By extracting 2D F1/F3 slices ((1)H/(1)H chemical shift correlation spectrum) at different (13)C chemical shift frequencies from the 3D (1)H/(13)C/(1)H spectrum, resonances of proton atoms located close to a specific carbon atom can be identified. Overall, the through-bond and through-space homonuclear/heteronuclear proximities determined from the 3D (1)H/(13)C/(1)H experiment would be useful to study the structure and dynamics of a variety of chemical and biological solids. PMID- 26801028 TI - Surface hopping investigation of the relaxation dynamics in radical cations. AB - Ionization processes can lead to the formation of radical cations with population in several ionic states. In this study, we examine the dynamics of three radical cations starting from an excited ionic state using trajectory surface hopping dynamics in combination with multiconfigurational electronic structure methods. The efficiency of relaxation to the ground state is examined in an effort to understand better whether fragmentation of cations is likely to occur directly on excited states or after relaxation to the ground state. The results on cyclohexadiene, hexatriene, and uracil indicate that relaxation to the ground ionic state is very fast in these systems, while fragmentation before relaxation is rare. Ultrafast relaxation is facilitated by the close proximity of electronic states and the presence of two- and three-state conical intersections. Examining the properties of the systems in the Franck-Condon region can give some insight into the subsequent dynamics. PMID- 26801029 TI - Infrared radiative decay dynamics from the gamma 1u ((3)P2), H 1u ((3)P1), and 1u ((1)D2) ion-pair states of I2 observed by a perturbation facilitated optical optical double resonance technique. AB - We report the spectroscopic and temporal analyses on the amplified spontaneous emission (ASE) from the single rovibrational levels of the Omega = 1u ion-pair series, gamma 1u ((3)P2), H 1u ((3)P1), and 1u ((1)D2), of I2 by using a perturbation facilitated optical-optical double resonance technique through the c (1)Pig ~ B (3)Pi(0u (+)) hyperfine mixed valence state as the intermediate state. The ASE detected in the infrared region was assigned to the parallel transitions from the Omega = 1u ion-pair states down to the nearby Omega = 1g ion-pair states. The subsequent ultraviolet (UV) fluorescence from the Omega = 1g states was also observed and the relative vibrational populations in the Omega = 1g states were derived through the Franck-Condon simulation of the intensity pattern of the vibrational progression. In the temporal profiles of the UV fluorescence, an obvious delay in the onset of the fluorescence was recognized after the excitation laser pulse. These results revealed that ASE is a dominant energy relaxation process between the Omega = 1u and 1g ion-pair states of I2. Finally, the lifetimes of the relevant ion-pair states were evaluated by temporal analyses of the UV fluorescence. The propensity was found which was the longer lifetime in the upper level of the ASE transitions tends to give intense ASE. PMID- 26801030 TI - Scattering study of the Ne + NeH(+)(v0 = 0, j0 = 0) -> NeH(+) + Ne reaction on an ab initio based analytical potential energy surface. AB - Initial state selected dynamics of the Ne + NeH(+)(v0 = 0, j0 = 0) -> NeH(+) + Ne reaction is investigated by quantum and statistical quantum mechanical (SQM) methods on the ground electronic state. The three-body ab initio energies on a set of suitably chosen grid points have been computed at CCSD(T)/aug-cc-PVQZ level and analytically fitted. The fitting of the diatomic potentials, computed at the same level of theory, is performed by spline interpolation. A collinear [NeHNe](+) structure lying 0.72 eV below the Ne + NeH(+) asymptote is found to be the most stable geometry for this system. Energies of low lying vibrational states have been computed for this stable complex. Reaction probabilities obtained from quantum calculations exhibit dense oscillatory structures, particularly in the low energy region and these get partially washed out in the integral cross section results. SQM predictions are devoid of oscillatory structures and remain close to 0.5 after the rise at the threshold thus giving a crude average description of the quantum probabilities. Statistical cross sections and rate constants are nevertheless in sufficiently good agreement with the quantum results to suggest an important role of a complex-forming dynamics for the title reaction. PMID- 26801031 TI - Geometry-dependent distributed polarizability models for the water molecule. AB - Geometry-dependent distributed polarizability models have been constructed by fits to ab initio calculations at the coupled cluster level of theory with up to noniterative triple excitations in an augmented triple-zeta quality basis set for the water molecule in the field of a point charge. The investigated models include (i) charge-flow polarizabilities between chemically bonded atoms, (ii) isotropic or anisotropic dipolar polarizabilities on oxygen atom or on all atoms, and (iii) combinations of models (i) and (ii). For each model, the polarizability parameters have been optimized to reproduce the induction energy of a water molecule polarized by a point charge successively occupying a grid of points surrounding the molecule. The quality of the models is ascertained by examining their ability to reproduce these induction energies as well as the molecular dipolar and quadrupolar polarizabilities. The geometry dependence of the distributed polarizability models has been explored by changing bond lengths and HOH angle to generate 125 molecular structures (reduced to 75 symmetry-unique ones). For each considered model, the distributed polarizability components have been fitted as a function of the geometry by a Taylor expansion in monomer coordinate displacements up to the sum of powers equal to 4. PMID- 26801032 TI - Hyperfine rather than spin splittings dominate the fine structure of the B (4)Sigma(-)-X (4)Sigma(-) bands of AlC. AB - Laser-induced fluorescence and wavelength resolved emission spectra of the B (4)Sigma(-)-X (4)Sigma(-) band system of the gas phase cold aluminum carbide free radical have been obtained using the pulsed discharge jet technique. The radical was produced by electron bombardment of a precursor mixture of trimethylaluminum in high pressure argon. High resolution spectra show that each rotational line of the 0-0 and 1-1 bands of AlC is split into at least three components, with very similar splittings and intensities in both the P- and R-branches. The observed structure was reproduced by assuming bbetaS magnetic hyperfine coupling in the excited state, due to a substantial Fermi contact interaction of the unpaired electron in the aluminum 3s orbital. Rotational analysis has yielded ground and excited state equilibrium bond lengths in good agreement with the literature and our own ab initio values. Small discrepancies in the calculated intensities of the hyperfine lines suggest that the upper state spin-spin constant lambda' is of the order of ~ 0.025-0.030 cm(-1). PMID- 26801033 TI - Unusual temperature dependence of the dissociative electron attachment cross section of 2-thiouracil. AB - At low energies (<3 eV), molecular dissociation is controlled by dissociative electron attachment for which the initial step, i.e., the formation of the transient negative ion, can be initiated by shape resonance or vibrational Feshbach resonance (VFR) mediated by the formation of a dipole bound anion. The temperature dependence for shape-resonances is well established; however, no experimental information is available yet on the second mechanism. Here, we show that the dissociation cross section for VFRs mediated by the formation of a dipole bound anion decreases as a function of a temperature. The change remains, however, relatively small in the temperature range of 370-440 K but it might be more pronounced at the extended temperature range. PMID- 26801034 TI - Path integral Liouville dynamics: Applications to infrared spectra of OH, water, ammonia, and methane. AB - Path integral Liouville dynamics (PILD) is applied to vibrational dynamics of several simple but representative realistic molecular systems (OH, water, ammonia, and methane). The dipole-derivative autocorrelation function is employed to obtain the infrared spectrum as a function of temperature and isotopic substitution. Comparison to the exact vibrational frequency shows that PILD produces a reasonably accurate peak position with a relatively small full width at half maximum. PILD offers a potentially useful trajectory-based quantum dynamics approach to compute vibrational spectra of molecular systems. PMID- 26801035 TI - Seeding approach to crystal nucleation. AB - We present a study of homogeneous crystal nucleation from metastable fluids via the seeding technique for four different systems: mW water, Tosi-Fumi NaCl, Lennard-Jones, and Hard Spheres. Combining simulations of spherical crystal seeds embedded in the metastable fluid with classical nucleation theory, we are able to successfully describe the nucleation rate for all systems in a wide range of metastability. The crystal-fluid interfacial free energy extrapolated to coexistence conditions is also in good agreement with direct calculations of such parameter. Our results show that seeding is a powerful technique to investigate crystal nucleation. PMID- 26801036 TI - First-principles study of the structural and dynamic properties of the liquid and amorphous Li-Si alloys. AB - We have performed density functional theory calculations and ab initio molecular dynamics to investigate the structures and dynamic properties of the liquid and amorphous LixSi alloys over a range of composition from x = 1.0 - 4.8. Our results show that Si atoms can form a variety of covalently bonded polyanions with diverse local bonding structures in the liquid alloys. Like in c-LiSi, Si atoms can form a continuous bond network in liquid Li1.0Si at 1050 K, while it gradually disintegrates into many smaller Si polyanions as the Li content increases in the alloys. The average sizes of Si polyanions in these liquid alloys were found to be relatively larger than those in their crystalline counterparts, which can even persist in the highly lithiated Li4.81Si alloy at 1500 K. Our results also show that amorphous LixSi alloys have similar local bonding structures but a largely increased short-range order as compared to their liquid counterparts. The differences between the average coordination number of each atomic pair in amorphous solids and that in the liquids are less than 1.1. Furthermore, our calculations reveal that Li and Si atoms can exhibit very distinct dynamic behaviors in the liquids and their diffusivities appear to be largely dependent on the chemical composition of the alloys. The diffusivity of Li was found to increase with the Li content in the alloys primarily because of the reduced interactions between Li and Si atoms, while the Si diffusivity also increases due to the gradual disintegration of the strongly interconnected Si bond network. The diffusivity of Li in amorphous LixSi was predicted to lie in the range between 10(-7) and 10(-9) cm(2)/s at 300 K, which is more than 20-fold larger than that of Si over the composition range considered. Our calculations further show that the diffusivities of both Li and Si can increase by two orders of magnitude as x increases from 1.0 to 3.57 in amorphous LixSi, indicating a more profound dependence on the alloy composition than those in the liquid state. PMID- 26801037 TI - Orientation-dependent energy level alignment and film growth of 2,7 diocty[1]benzothieno[3,2-b]benzothiophene (C8-BTBT) on HOPG. AB - Combining ultraviolet photoemission spectroscopy, X-ray photoemission spectroscopy, atomic force microscopy, and X-ray diffraction measurements, we performed a systematic investigation on the correlation of energy level alignment, film growth, and molecular orientation of 2,7-diocty[1]benzothieno[3,2 b]benzothiophene (C8-BTBT) on highly oriented pyrolytic graphite. The molecules lie down in the first layer and then stand up from the second layer. The ionization potential shows a sharp decrease from the lying down region to the standing up region. When C8-BTBT molecules start standing up, unconventional energy level band-bending-like shifts are observed as the film thickness increases. These shifts are ascribed to gradual decreasing of the molecular tilt angle about the substrate normal with the increasing film thickness. PMID- 26801038 TI - Dielectric properties of crystalline organic molecular films in the limit of zero overlap. AB - We present the calculation of the static dielectric susceptibility tensor and dipole field sums in thin molecular films in the well-defined limit of zero intermolecular overlap. Microelectrostatic and charge redistribution approaches are applied to study the evolution of dielectric properties from one to a few molecular layers in films of different conjugated molecules with organic electronics applications. Because of the conditional convergence of dipolar interactions, dipole fields depend on the shape of the sample and different values are found in the middle layer of a thick film and in the bulk. The shape dependence is eliminated when depolarization is taken into account, and the dielectric tensor of molecular films converges to the bulk limit within a few molecular layers. We quantify the magnitude of surface effects and interpret general trends among different systems in terms of molecular properties, such as shape, polarizability anisotropy, and supramolecular organization. A connection between atomistic models for molecular dielectrics and simpler theories for polarizable atomic lattices is also provided. PMID- 26801039 TI - Insights into the dominant factors of porous gold for CO oxidation. AB - Three different porous Au catalysts that exhibit high catalytic activity for CO oxidation were prepared by the leaching of Al from an intermetallic compound, Al2Au, with 10 wt. %-NaOH, HNO3, or HCl aqueous solutions. The catalysts were investigated using Brunauer-Emmett-Teller measurements, synchrotron X-ray powder diffraction, hard X-ray photoelectron spectroscopy, field emission scanning electron microscopy, and transmission electron microscopy (TEM). Broad diffraction peaks generated during the leaching process correlated with high activity for all the porous Au catalysts. CO oxidation catalyzed by porous Au leached with NaOH and HNO3 is considered to be dominated by different mechanisms at low (< 320 K) and high (> 370 K) temperatures. Activity in the low-temperature region is mainly attributed to the perimeter interface between residual Al species (AlOx) and porous Au, whereas activity in the high-temperature region results from a high density of lattice defects such as twins and dislocations, which were evident from diffraction peak broadening and were observed with high resolution TEM in the porous Au leached with NaOH. It is proposed that atoms located at lattice defects on the surfaces of porous Au are the active sites for catalytic reactions. PMID- 26801040 TI - Homogeneous and inhomogeneous broadenings and the Voigt line shapes in the phase resolved and intensity sum-frequency generation vibrational spectroscopy. AB - In this report, we show that the ability to measure the sub-1 cm(-1) resolution phase-resolved and intensity high-resolution broadband sum frequency generation vibrational spectra of the -CN stretch vibration of the Langmuir-Blodgett (LB) monolayer of the 4-n-octyl-4'-cyanobiphenyl (8CB) on the z-cut alpha-quartz surface allows the direct comparison and understanding of the homogeneous and inhomogeneous broadenings in the imaginary and intensity SFG vibrational spectral line shapes in detail. The difference of the full width at half maximum (FWHM) of the imaginary and intensity sum-frequency generation vibrational spectroscopy spectra of the same vibrational mode is the signature of the Voigt line shape and it measures the relative contribution to the overall line shape from the homogeneous and inhomogeneous broadenings in SFG vibrational spectra. From the phase-resolved and intensity spectra, we found that the FWHM of the 2238.00 +/- 0.02 cm(-1) peak in the phase-resolved imaginary and intensity spectra is 19.2 +/ 0.2 cm(-1) and 21.6 +/- 0.4 cm(-1), respectively, for the -CN group of the 8CB LB monolayer on the z-cut alpha-quartz crystal surface. The FWHM width difference of 2.4 cm(-1) agrees quantitatively with a Voigt line shape with a homogeneous broadening half width of Gamma = 5.29 +/- 0.08 cm(-1) and an inhomogeneous standard derivation width Deltaomega = 5.42 +/- 0.07 cm(-1). These results shed new lights on the understanding and interpretation of the line shapes of both the phase-resolved and the intensity SFG vibrational spectra, as well as other incoherent and coherent spectroscopic techniques in general. PMID- 26801041 TI - Entropically induced asymmetric passage times of charged tracers across corrugated channels. AB - We analyze the diffusion of charged and neutral tracers suspended in an electrolyte embedded in a channel of varying cross section. Making use of systematic approximations, the diffusion equation governing the motion of tracers is mapped into an effective 1D equation describing the dynamics along the longitudinal axis of the channel where its varying-section is encoded as an effective entropic potential. This simplified approach allows us to characterize tracer diffusion under generic confinement by measuring their mean first passage time (MFPT). In particular, we show that the interplay between geometrical confinement and electrostatic interactions strongly affect the MFTP of tracers across corrugated channels hence leading to alternative means to control tracers translocation across charged pores. Finally, our results show that the MFPTs of a charged tracer in opposite directions along an asymmetric channel may differ We expect our results to be relevant for biological as well synthetic devices whose dynamics is controlled by the detection of diluted tracers. PMID- 26801042 TI - Self-assembly of colloidal bands driven by a periodic external field. AB - We study the formation of bands of colloidal particles driven by periodic external fields. Using Brownian dynamics, we determine the dependence of the band width on the strength of the particle interactions and on the intensity and periodicity of the field. We also investigate the switching (field-on) dynamics and the relaxation times as a function of the system parameters. The observed scaling relations were analyzed using a simple dynamic density-functional theory of fluids. PMID- 26801043 TI - A molecular dynamics study of the breathing and deforming modes of the spherical ionic SDS and nonionic C12E8 micelles. AB - In order to investigate shape of the micelles and its thermal fluctuations, molecular dynamics calculations have been performed for spherical ionic sodium dodecyl sulfate (SDS) and nonionic octaethyleneglycol monododecyl ether (C12E8) micelles. New statistical functions suitable for extracting the fluctuations of the shape of the spherical micelles were defined using spherical harmonics and Legendre polynomials. The breathing and deforming modes of the SDS and C12E8 micelles were analyzed in detail based on these new functions. The elastic nature of the micelle core was also discussed. The present analysis gives a new molecular picture that the micelle shape is a superposition of the various kinds of breathing and deforming modes, and each mode has a specific relaxation time of the shape fluctuation. PMID- 26801044 TI - Aggregation dynamics of rigid polyelectrolytes. AB - Similarly charged polyelectrolytes are known to attract each other and aggregate into bundles when the charge density of the polymers exceeds a critical value that depends on the valency of the counterions. The dynamics of aggregation of such rigid polyelectrolytes are studied using large scale molecular dynamics simulations. We find that the morphology of the aggregates depends on the value of the charge density of the polymers. For values close to the critical value, the shape of the aggregates is cylindrical with height equal to the length of a single polyelectrolyte chain. However, for larger values of charge, the linear extent of the aggregates increases as more and more polymers aggregate. In both the cases, we show that the number of aggregates decrease with time as power laws with exponents that are not numerically distinguishable from each other and are independent of charge density of the polymers, valency of the counterions, density, and length of the polyelectrolyte chain. We model the aggregation dynamics using the Smoluchowski coagulation equation with kernels determined from the molecular dynamics simulations and justify the numerically obtained value of the exponent. Our results suggest that once counterions condense, effective interactions between polyelectrolyte chains short-ranged and the aggregation of polyelectrolytes are diffusion-limited. PMID- 26801045 TI - Modeling generic aspects of ideal fibril formation. AB - Many different proteins self-aggregate into insoluble fibrils growing apically by reversible addition of elementary building blocks. But beyond this common principle, the modalities of fibril formation are very disparate, with various intermediate forms which can be reshuffled by minor modifications of physico chemical conditions or amino-acid sequences. To bypass this complexity, the multifaceted phenomenon of fibril formation is reduced here to its most elementary principles defined for a linear prototype of fibril. Selected generic features, including nucleation, elongation, and conformational recruitment, are modeled using minimalist hypotheses and tools, by separating equilibrium from kinetic aspects and in vitro from in vivo conditions. These reductionist approaches allow to bring out known and new rudiments, including the kinetic and equilibrium effects of nucleation, the dual influence of elongation on nucleation, the kinetic limitations on nucleation and fibril numbers, and the accumulation of complexes in vivo by rescue from degradation. Overlooked aspects of these processes are also pointed: the exponential distribution of fibril lengths can be recovered using various models because it is attributable to randomness only. It is also suggested that the same term "critical concentration" is used for different things, involved in either nucleation or elongation. PMID- 26801046 TI - Publisher's Note: "Surface energy fluctuation effects in single crystals of DNA functionalized nanoparticles" [J. Chem. Phys. 143, 243156 (2015)]. PMID- 26801047 TI - Publisher's Note: "Matrix-isolation and ab initio study of HKrCCCl and HXeCCCl" [J. Chem. Phys. 143, 244319 (2015)]. PMID- 26801049 TI - Hyper-IgE Syndrome in an Infant. AB - BACKGROUND: Hyper-immunoglobulin E syndrome (HIES) is a rare primary immunodeficiency disorder that affects multiple systems. One of the early findings is a papulopustular rash, which has a wide differential diagnosis. METHOD: The authors report the case of a male newborn diagnosed with HIES. He presented with papulopustular dermatitis on the scalp. The authors also present a review of current theory on the pathophysiology, clinical presentation, and management of HIES. CONCLUSION: Although HIES is a multisystem disorder, many of the manifestations of HIES may present after the neonatal period. The cutaneous manifestations of HIES are usually present shortly after birth, and the presentation of pustules in a newborn may be one of the reasons a dermatologist would be asked to assess a patient in the neonatal period. PMID- 26801048 TI - Multiplex sequencing of bacterial artificial chromosomes for assembling complex plant genomes. AB - Hierarchical shotgun sequencing remains the method of choice for assembling high quality reference sequences of complex plant genomes. The efficient exploitation of current high-throughput technologies and powerful computational facilities for large-insert clone sequencing necessitates the sequencing and assembly of a large number of clones in parallel. We developed a multiplexed pipeline for shotgun sequencing and assembling individual bacterial artificial chromosomes (BACs) using the Illumina sequencing platform. We illustrate our approach by sequencing 668 barley BACs (Hordeum vulgare L.) in a single Illumina HiSeq 2000 lane. Using a newly designed parallelized computational pipeline, we obtained sequence assemblies of individual BACs that consist, on average, of eight sequence scaffolds and represent >98% of the genomic inserts. Our BAC assemblies are clearly superior to a whole-genome shotgun assembly regarding contiguity, completeness and the representation of the gene space. Our methods may be employed to rapidly obtain high-quality assemblies of a large number of clones to assemble map-based reference sequences of plant and animal species with complex genomes by sequencing along a minimum tiling path. PMID- 26801050 TI - Data on diabetes care should be used to identify poorly performing CCGs, say MPs. PMID- 26801051 TI - Emergency department visits and hospitalisations for adverse events related to dietary supplements are common. PMID- 26801052 TI - USE OF A SIMPLE THERMALISED NEUTRON FIELD FOR QUALITY ACCEPTANCE OF WHOLE BODY TLDS. AB - The individual monitoring service of Public Health England (PHE) uses HarshawTM whole-body and extremity thermoluminescent dosemeters (TLDs) with high sensitivity lithium fluoride LiF:Mg,Cu,P, together with Harshaw 8800TM automated readers. The neutron-insensitive, (6)Li-depleted variety of TLD material is used by PHE because the service provides separate neutron and photon dosemeters. The neutron dosemeters are not sensitive to photons and vice versa Since insensitivity to neutrons is a supply requirement for TLDs, there is a need to test every new (annual) consignment for this. Because it is thermal neutrons that produce a response in (6)Li TLDs, a thermal field is needed. To this end, PHE has adopted the simple approach of sandwiching the TLDs between two ISO water-filled slab phantoms. In this arrangement, the fast neutrons from an Am-Be source are effectively thermalised. Details of the method are given, together with the results of supporting MCNP calculations and some typical results. PMID- 26801053 TI - Ireland is to install supervised injecting rooms. PMID- 26801054 TI - A DNA-binding Molecule Targeting the Adaptive Hypoxic Response in Multiple Myeloma Has Potent Antitumor Activity. AB - Multiple myeloma is incurable and invariably becomes resistant to chemotherapy. Although the mechanisms remain unclear, hypoxic conditions in the bone marrow have been implicated in contributing to multiple myeloma progression, angiogenesis, and resistance to chemotherapy. These effects occur via adaptive cellular responses mediated by hypoxia-inducible transcription factors (HIF), and targeting HIFs can have anticancer effects in both solid and hematologic malignancies. Here, it was found that in most myeloma cell lines tested, HIF1alpha, but not HIF2alpha expression was oxygen dependent, and this could be explained by the differential expression of the regulatory prolyl hydroxylase isoforms. The anti-multiple myeloma effects of a sequence-specific DNA-binding pyrrole-imidazole (Py-Im) polyamide (HIF-PA), which disrupts the HIF heterodimer from binding to its cognate DNA sequences, were also investigated. HIF-PA is cell permeable, localizes to the nuclei, and binds specific regions of DNA with an affinity comparable with that of HIFs. Most of the multiple myeloma cells were resistant to hypoxia-mediated apoptosis, and HIF-PA treatment could overcome this resistance in vitro. Using xenograft models, it was determined that HIF-PA significantly decreased tumor volume and increased hypoxic and apoptotic regions within solid tumor nodules and the growth of myeloma cells engrafted in the bone marrow. This provides a rationale for targeting the adaptive cellular hypoxic response of the O2-dependent activation of HIFalpha using polyamides. IMPLICATIONS: Py-Im polyamides target and disrupt the adaptive hypoxic responses in multiple myeloma cells that may have clinical significance as a therapeutic strategy to treat myeloma engrafted in the bone marrow microenvironment. PMID- 26801056 TI - Glucagon-like peptide-1 agonists combating clozapine-associated obesity and diabetes. AB - Clozapine is the most effective antipsychotic, but its use is tempered by adverse metabolic effects such as weight gain, glucose intolerance and type II diabetes. Current interventions do not facilitate compelling or sustained improvement in metabolic status. Recent studies suggest that glucagon-like peptide-1 (GLP-1) may play a key role in clozapine's metabolic effects, possibly suggesting that clozapine-associated obesity and diabetes are mediated independently through reduced GLP-1. As a result, GLP-1 agonists could show promise in reversing antipsychotic-induced metabolic derangements, providing mechanistic justification that they may represent a novel approach to treat, and ultimately prevent, both diabetes and obesity in patients on clozapine. GLP-1 agonists are already used for diabetes, and they provide a unique combination of glycaemic improvement and metabolically relevant weight loss in diabetic and non-diabetic patients, in the context of a currently favourable safety profile. Using GLP-1 agonists for clozapine-associated obesity and diabetes could be a potentially effective intervention that may reduce cardiometabolic morbidity and mortality in this vulnerable patient population. PMID- 26801055 TI - Role of Coronary Artery Calcium Score of Zero and Other Negative Risk Markers for Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis (MESA). AB - BACKGROUND: Limited attention has been paid to negative cardiovascular disease (CVD) risk markers despite their potential to improve medical decision making. We compared 13 negative risk markers using diagnostic likelihood ratios (DLRs), which model the change in risk for an individual after the result of an additional test. METHODS AND RESULTS: We examined 6814 participants from the Multi-Ethnic Study of Atherosclerosis. Coronary artery calcium score of 0, carotid intima-media thickness <25th percentile, absence of carotid plaque, brachial flow-mediated dilation >5% change, ankle-brachial index >0.9 and <1.3, high-sensitivity C-reactive protein <2 mg/L, homocysteine <10 umol/L, N-terminal pro-brain natriuretic peptide <100 pg/mL, no microalbuminuria, no family history of coronary heart disease (any/premature), absence of metabolic syndrome, and healthy lifestyle were compared for all and hard coronary heart disease and all CVD events over the 10-year follow-up. Models were adjusted for traditional CVD risk factors. Among all negative risk markers, coronary artery calcium score of 0 was the strongest, with an adjusted mean DLR of 0.41 (SD, 0.12) for all coronary heart disease and 0.54 (SD, 0.12) for CVD, followed by carotid intima-media thickness <25th percentile (DLR, 0.65 [SD, 0.04] and 0.75 [SD, 0.04], respectively). High-sensitivity C-reactive protein <2 mg/L and normal ankle brachial index had DLRs >0.80. Among clinical features, absence of any family history of coronary heart disease was the strongest (DLRs, 0.76 [SD, 0.07] and 0.81 [SD, 0.06], respectively). Net reclassification improvement analyses yielded similar findings, with coronary artery calcium score of 0 resulting in the largest, most accurate downward risk reclassification. CONCLUSIONS: Negative results of atherosclerosis-imaging tests, particularly coronary artery calcium score of 0, resulted in the greatest downward shift in estimated CVD risk. These results may help guide discussions on the identification of individuals less likely to receive net benefit from lifelong preventive pharmacotherapy. PMID- 26801058 TI - Arenimonas aestuarii sp. nov., isolated from estuary sediment. AB - A novel species of the genus Arenimonas, represented by strain S2-21T, was isolated from an estuary of Asan in South Korea. Cells of strain S2-21T were Gram stain-negative, aerobic, non-motile rods that were oxidase- and catalase positive. Growth of strain S2-21T was observed at 15-40 degrees C (optimum, 25 30 degrees C), at pH 7.0-8.0 (optimum, pH 7.0) and in the presence of 0-2.0 % (w/v) NaCl (optimum, 0 %). The major cellular fatty acids were iso-C15 : 0, C11 : 0 3-OH, iso-C16 : 0, summed feature 9 (comprising iso-C17 : 1omega9c and/or C16 : 0 10-methyl), anteiso-C17 : 0 and iso-C11 : 0. The only respiratory quinone detected was ubiquinone-8 (Q-8) and the major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylmethylethanol and two unknown phospholipids. The G+C content of the genomic DNA was 62.2 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain S2-21T formed a tight phyletic lineage with Arenimonas donghaensis HO3-R19T within the genus Arenimonas. Strain S2-21T was related most closely to A. donghaensis HO3-R19T at 98.1 % 16S rRNA gene sequence similarity and the mean DNA-DNA relatedness value between strain S2-21T and the type strain of A. donghaensis was 23.6 +/- 2.2 %. On the basis of phenotypic, chemotaxonomic and molecular features, strain S2-21T is considered to represent a novel species of the genus Arenimonas, for which the name Arenimonas aestuarii sp. nov. is proposed. The type strain is S2-21T ( = KACC 18504T = JCM 31129T). PMID- 26801057 TI - Analysis of dynamic protein carbonylation in rice embryo during germination through AP-SWATH. AB - Seed germination is an important aspect of the plant life cycle, during which, reactive oxygen species (ROS) accumulate. The accumulation of ROS results in an increase in protein oxidation of which carbonylation is the most canonical one. However, there is insufficient information concerning protein oxidation, especially carbonylation and its contribution to seed germination. In this study, biotin hydrazide labeled chromatography combined with sequential window acquisition of all theoretical fragment ion spectra (SWATH) method was used to analyze the dynamic pattern of protein carbonylation in rice embryos during germination. A total of 1872 unique proteins were quantified, among which 288 carbonylated peptides corresponding to 144 proteins were determined based on the filtering through mass shifts of modified amino acids. In addition, 66 carbonylated proteins were further analyzed based on their carbonylation intensity in four stages of germination. These identified carbonylated proteins were mainly involved in maintaining the levels of ROS, abscisic acid and seed reserves. Remarkably, a peroxiredoxin was found with 23 unique carbonylated peptides, and the expression of which was consistent with its increased activity. This study describes the dynamic pattern of carbonylated proteins during seed germination, and may help to further understand the biochemical mechanisms on this process. PMID- 26801059 TI - Optimal Combinations of Isometric Normalization Tests for the Production of Maximum Voluntary Activation of the Shoulder Muscles. AB - OBJECTIVE: To identify the smallest combinations of maximum voluntary isometric contraction (MVIC) tests that produce near-maximum voluntary activation (MVA) for a large proportion of participants for the shoulder girdle muscles. DESIGN: Cross sectional study. SETTING: Research center. PARTICIPANTS: Healthy participants (N=38). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The electromyography of 12 shoulder muscles was recorded while participants performed 15 MVIC tests. The smallest combinations of MVIC tests that met our acceptance criterion (ie, produce 90% of MVA for 90% of participants) were identified. Optimal combinations were identified for each of the 12 muscles individually and for the 12 muscles simultaneously. Electromyographic activation levels of the 95th highest percentile obtained with our optimal combinations and with the Four Normalization Tests previously recommended were compared using paired t tests. RESULTS: Between 2 and 6 MVIC tests were required for each of the 12 muscles, and 12 MVIC tests were required for the 12 muscles to meet the acceptance criterion. These optimal combinations produced electromyographic activation levels of the 95th highest percentile comprised between 97% and 100% of MVA. These electromyographic activation levels were significantly higher than the electromyographic activation levels obtained with the Four Normalization Tests. CONCLUSIONS: Although the number of MVIC tests to normalize 12 shoulder muscles was increased compared with previous recommendations, the proposed method ensures that near-MVA (>90%) was obtained for a large proportion of participants (>90%). Moreover, because electromyographic activation levels of the 95th highest percentile were at least 97% of MVA, the identified combinations could reduce the interparticipant variability. The proposed combinations could help to improve electromyographic normalization and therefore reduce the misinterpretations regarding shoulder muscle activation levels. PMID- 26801060 TI - Gene Therapy in Cardiac Surgery: Clinical Trials, Challenges, and Perspectives. AB - The concept of gene therapy was introduced in the 1970s after the development of recombinant DNA technology. Despite the initial great expectations, this field experienced early setbacks. Recent years have seen a revival of clinical programs of gene therapy in different fields of medicine. There are many promising targets for genetic therapy as an adjunct to cardiac surgery. The first positive long term results were published for adenoviral administration of vascular endothelial growth factor with coronary artery bypass grafting. In this review we analyze the past, present, and future of gene therapy in cardiac surgery. The articles discussed were collected through PubMed and from author experience. The clinical trials referenced were found through the Wiley clinical trial database (http://www.wiley.com/legacy/wileychi/genmed/clinical/) as well as the National Institutes of Health clinical trial database (Clinicaltrials.gov). PMID- 26801061 TI - An individualized predictor of health and disease using paired reference and target samples. AB - BACKGROUND: Consider the problem of designing a panel of complex biomarkers to predict a patient's health or disease state when one can pair his or her current test sample, called a target sample, with the patient's previously acquired healthy sample, called a reference sample. As contrasted to a population averaged reference this reference sample is individualized. Automated predictor algorithms that compare and contrast the paired samples to each other could result in a new generation of test panels that compare to a person's healthy reference to enhance predictive accuracy. This paper develops such an individualized predictor and illustrates the added value of including the healthy reference for design of predictive gene expression panels. RESULTS: The objective is to predict each subject's state of infection, e.g., neither exposed nor infected, exposed but not infected, pre-acute phase of infection, acute phase of infection, post-acute phase of infection. Using gene microarray data collected in a large scale serially sampled respiratory virus challenge study we quantify the diagnostic advantage of pairing a person's baseline reference with his or her target sample. The full study consists of 2886 microarray chips assaying 12,023 genes of 151 human volunteer subjects under 4 different inoculation regimes (HRV, RSV, H1N1, H3N2). We train (with cross-validation) reference-aided sparse multi-class classifier algorithms on this data to show that inclusion of a subject's reference sample can improve prediction accuracy by as much as 14 %, for the H3N2 cohort, and by at least 6 %, for the H1N1 cohort. Remarkably, these gains in accuracy are achieved by using smaller panels of genes, e.g., 39 % fewer for H3N2 and 31 % fewer for H1N1. The biomarkers selected by the predictors fall into two categories: 1) contrasting genes that tend to differentially express between target and reference samples over the population; 2) reinforcement genes that remain constant over the two samples, which function as housekeeping normalization genes. Many of these genes are common to all 4 viruses and their roles in the predictor elucidate the function that they play in differentiating the different states of host immune response. CONCLUSIONS: If one uses a suitable mathematical prediction algorithm, inclusion of a healthy reference in biomarker diagnostic testing can potentially improve accuracy of disease prediction with fewer biomarkers. PMID- 26801062 TI - Circulating soluble receptor for advanced glycation end products is decreased and inversely associated with acute phase response in chronic spontaneous urticaria. AB - BACKGROUND: Activation of receptor for advanced glycation end products (RAGE) leads to the proinflammatory response and the release of its soluble form (sRAGE) which appears to function as an anti-inflammatory feedback mechanism. AIM: To determine serum sRAGE concentration in CSU patients and its association with C reactive protein (CRP) concentration, a nonspecific inflammatory marker of the disease activity. METHODS: Concentrations of sRAGE and CRP were measured in serum of CSU patients and compared with the healthy controls. RESULTS: Serum sRAGE concentrations were significantly decreased in CSU patients, especially those more severely affected. In addition, significant inverse correlations were observed between sRAGE and CRP concentrations. CONCLUSIONS: Down-regulation of sRAGE and its association with acute phase response suggest a role for RAGE activation in the pathogenesis of CSU. It seems that lower serum sRAGE concentration may enhance the urticarial processes. PMID- 26801063 TI - Comparative immunogenicity of hepatitis B vaccine with different dosages and schedules in healthy young adults in China. AB - OBJECTIVES: To compare immunogenicity of hepatitis B vaccine between the standard 3-dose (20 MUg) and 2-dose with higher-dosage (60 MUg) regimens in healthy young adults and evaluate the safety profile. METHODS: A randomized, parallel-group clinical trial was conducted among healthy young adults aged 18-25 years. Subjects were randomly assigned to three groups. One group was administered hepatitis B vaccine with the standard regimen of 0-1-6 month (20 MUg) and other groups were immunized with regimens of 0-1 or 0-2 month (60 MUg) respectively. Serum samples were collected at 1 month after a series vaccination and 12 months after the first-dose inoculation for anti-HBs antibody measurement with a Chemiluminescent Microparticle ImmunoAssay (CMIA). RESULTS: The seroprotection rates in 20 MUg (0-1-6 month), 60 MUg (0-1 month) and 60 MUg (0-2 month) groups were 100, 93.64 and 99.19% at month 7/2/3, and 100, 96.04 and 95.90% at month 12, respectively. There were no significant differences among three vaccine groups (p>0.05). The geometric mean concentration (GMC) of anti-HBs was significantly higher in 20 MUg (0-1-6 month) group than that in 60 MUg (0-1 month) group at month 7/2 (1847.99 vs. 839.27 mIU/ml, p=0.004), but was similar to that in 60MUg (0-2 month) group at month 7/3 (1847.99 vs. 1244.80 mIU/ml, p=0.138). At month 12, the GMC in 20 MUg (0-1-6 month) group was significantly higher than those of other groups (1456.63 vs. 256.30, 235.15 mIU/ml, respectively, p<0.001). The total incidence of injection-site or systemic adverse reactions was <3%. CONCLUSIONS: A 2-dose with higher-dosage hepatitis B vaccine regimens are comparable to the standard 3-dose regimen in terms of immunogenicity except a relatively rapid decline in GMC levels which are associated with the longevity of protection. All formulations of hepatitis B vaccine were well tolerated. CLINICALTRIALS.GOV IDENTIfiER: NCT02203357. PMID- 26801064 TI - Surface display of a borrelial lipoprotein on meningococcal outer membrane vesicles. AB - Outer Membrane Vesicles (OMVs) are gaining attention as vaccine candidates. The successful expression of heterologous antigens in OMVs, with the OMV functioning both as adjuvant and delivery vehicle, has greatly enhanced their vaccine potential. Since there are indications that surface exposed antigens might induce a superior immune response, targeting of heterologous antigens to the OMV surface is of special interest. Several systems for surface display of heterologous antigens on OMVs have been developed. However, these systems have not been used to display lipidated membrane-associated proteins known as lipoproteins, which are emerging as key targets for protective immunity. We were therefore interested to see whether we could express a foreign lipoprotein on the outer surface of OMVs. When outer surface protein A (OspA), a borrelial surface-exposed lipoprotein, was expressed in meningococci, it was found that although OspA was present in OMVs, it was no longer surface-exposed. Therefore, a set of fusions of OspA to different regions of factor H binding protein (fHbp), a meningococcal surface-exposed lipoprotein, were designed and tested for their surface-exposure. An N-terminal part of fHbp was found to be necessary for the successful surface display of OspA on meningococcal OMVs. When mice were immunized with this set of OMVs, an OspA-specific antibody response was only elicited by OMVs with clearly surface-exposed OspA, strengthening the idea that the exact positioning of an antigen in the OMV affects the immune response. This method for the surface display of heterologous lipoproteins on OMVs is a step forward in the development of OMVs as a vaccine platform. PMID- 26801065 TI - Evaluation of measles-rubella vaccination for mothers in early puerperal phase. AB - BACKGROUND: The postpartum period is an ideal opportunity to vaccinate mothers with inadequate immunity to vaccine-preventable diseases including measles and rubella. METHODS: A prospective study of measles-rubella (MR) vaccination in the early puerperal phase was conducted in 171 mothers, who had insufficient antibody titers when screened for immunity to measles (<= 1:4 on the neutralization test [NT]) or rubella (<= 1:16 on the hemagglutination inhibition [HI] test) during pregnancy. To evaluate the efficacy of MR vaccination in the postpartum period, we determined their post-vaccination antibody titers and immune responses to vaccination, and investigated the association between these and their prolactin (PRL) levels and Th1/Th2 ratios at the time of vaccination. We also examined the passage of viral RNA and antigen into breast milk. RESULTS: Of the 169 participants who completed the study schedule, 117 and 101 had low antibody titers against measles and rubella, respectively. In the measles-seronegative group, the antibody-positive rate was 87% on the NT assay, and the NT geometric mean antibody titer was 11.4 (95% confidence interval [CI], 10.0-13.0). In the rubella-seronegative group, the antibody-positive rate was 88% on the HI test assay, and the HI geometric mean antibody titer was 64.0 (95% CI, 53.9-76.0). There was no association between the post-vaccination antibody titers and the PRL levels or Th1/Th2 ratios at the time of vaccination. In the rubella-seronegative group, subjects with higher Th1/Th2 ratios showed higher rates of responsiveness than those with lower ratios (P=0.045). Although measles virus RNA was isolated from the breast milk of two vaccinated mothers, breastfeeding was not associated with clinical disease in any infants. CONCLUSION: MR vaccination in the early puerperal phase is considered an effective way to prevent the diseases, regardless of the mother's immunological status and hormonal milieu. PMID- 26801066 TI - Assisted reproductive technology and risk of adverse obstetric outcomes in dichorionic twin pregnancies: a systematic review and meta-analysis. AB - OBJECTIVE: To examine whether dichorionic twin pregnancies after assisted reproductive technology (ART) were at higher risk of adverse obstetric outcomes compared with those conceived naturally. DESIGN: Meta-analysis. SETTING: University-affiliated teaching hospital. PATIENT(S): Dichorionic twin pregnancies conceived with ART and naturally. INTERVENTION(S): Studies comparing obstetric outcomes in dichorionic twin pregnancies conceived by ART and naturally were identified by searching PubMed, Google Scholar, Cochrane Libraries, and Chinese databases through July 2015 with no restrictions. Either a fixed-effects or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators. MAIN OUTCOME MEASURE(S): Maternal complications and adverse pregnancy outcomes. RESULT(S): Fifteen cohort studies involving 6,420 dichorionic twins after ART and 13,650 dichorionic twins conceived naturally were included. Most of maternal complications were similar in both groups, but placenta previa (relative risk [RR] = 2.99, 95% confidence interval [CI] 1.51-5.92; I(2) = 0) was significantly more common in the ART group. For neonatal outcomes, the ART group experienced higher risk of preterm birth (RR = 1.13, 95% CI 1.00-1.29; I(2) = 75%), very preterm birth (RR = 1.39, 95% CI 1.07-1.82; I(2) = 71%), low birth weight (RR = 1.11, 95% CI 1.00-1.23; I(2) = 61%), and congenital malformations (RR = 1.26, 95% CI 1.09-1.46; I(2) = 26%). In addition, the ART group had a higher proportion of elective cesarean sections (RR = 1.79, 95% CI 1.49-2.16; I(2) = 60%), but had a similar proportion for emergency cesarean sections. Relevant heterogeneity moderators have been identified by subgroup analysis. No evidence of publication bias was observed. CONCLUSION(S): The rates of placenta previa, elective cesarean section, preterm birth, very preterm birth, low birth weight, and congenital malformations were significantly higher in dichorionic twin pregnancies after ART. PMID- 26801067 TI - In-bag manual versus uncontained power morcellation for laparoscopic myomectomy: randomized controlled trial. AB - OBJECTIVE: To evaluate whether manualin-bag morcellation could be efficiently proposed as alternative to the uncontained power technique. DESIGN: Randomized controlled trial. SETTING: Academic hospital. PATIENT(S): One hundred fifty-two premenopausal women eligible for myomectomy were screened, and 104 were randomized. INTERVENTION(S): Patients were randomized into two groups. In the experimental group, "in-bag" protected morcellation was performed. In the control group, patients were treated by uncontained power myoma removal. MAIN OUTCOME MEASURE(S): The primary endpoint was the comparison of morcellation operative time (MOT). The secondary endpoints were the comparisons of total operative time (TOT), simplicity of morcellation (as defined by the surgeon using a visual analogue scale scale), intraoperative blood loss, rate of complications, and postoperative outcomes. RESULT(S): A sample size of 51 per group (n = 102) was planned. Between March 2014 and January 2015, patients were randomized as follows: 53 to the experimental group and 51 to the control group. Most demographic characteristics were similar across groups. MOT was observed to be similar in both study groups (16.18 +/- 8.1 vs. 14.35 +/- 7.8 minutes, in the experimental and control groups, respectively). Fibroid size was identified as the principal factor influencing morcellation time (Pearson coefficient 0.484 vs. 0.581, in the experimental and control groups, respectively). No significant difference in TOT, simplicity of morcellation, delta Hb, postoperative pain, and postoperative outcomes were observed between groups. CONCLUSION(S): The protected manual in-bag morcellation technique represents a time-efficient and feasible alternative, which does not interfere with surgical outcomes in women undergoing laparoscopic myomectomy. CLINICAL TRIAL REGISTRATION: NCT02086435. PMID- 26801068 TI - Women infected with human immunodeficiency virus type 1 have poorer assisted reproduction outcomes: a case-control study. AB - OBJECTIVE: To compare the efficacy of assisted reproductive technology (ART) in women infected with human immunodeficiency virus type 1 (HIV-1) versus HIV negative controls. DESIGN: Retrospective case-control study. SETTING: University hospital ART unit. PATIENT(S): Eighty-two women infected with HIV-1 and 82 women as seronegative controls. INTERVENTION(S): Ovarian stimulation, oocytes retrieval, standard in vitro fertilization (IVF) or intracytoplasmic sperm injection, embryo transfer. MAIN OUTCOME MEASURE(S): Clinical pregnancies and live-birth rates. RESULT(S): After oocyte retrieval, all women infected with HIV 1 infected were matched 1:1 to HIV-negative controls according to the following criteria: date of ART attempt, age, parity, main cause of infertility, ART technique, and rank of attempt. Only the first IVF cycle during the study period was considered for each couple. We found no statistically significant differences between the two groups for ovarian stimulation data, fertilization rate, or average number of embryos transferred. The clinical pregnancy rate per transfer was statistically significantly lower for the cases compared with the controls (12% vs. 32%), as were the implantation rate (10% vs. 21%) and the live-birth rate (7% vs. 19%). CONCLUSION(S): In one of the largest studies to pair six factors that influence the results of ART, HIV infection in women was associated with poorer outcomes after ART. These results suggest that women with controlled HIV-1-infection should be counseled not to delay ART in cases of self insemination failure or other causes of infertility. Fertility preservation by vitrification of oocytes in women whose pregnancy should be delayed may be an important future consideration. PMID- 26801069 TI - Position statement on West Nile virus: a committee opinion. AB - Although there is currently no definitive evidence linking West Nile virus (WNV) transmission with reproductive cells, it is recommended that practitioners defer gamete donors who have confirmed or suspected WNV infections. This document replaces the previously published document of the same name, last published in 2012 (Fertil Steril 2012;98:e15-6). PMID- 26801072 TI - Participants' employment status and experiences in the year after the Experienced Involvement training. AB - BACKGROUND: Peer support workers (PSWs) are an emerging workforce within the Swiss mental health system. The 'Experienced Involvement' (EX-IN) training programmes prepare and certify individuals who have experienced mental health problems to work as PSWs. AIMS: This study examined the influence of EX-IN training on participants' employment status and their experiences in the year after training. METHOD: We employed quantitative and qualitative methods. Quantitative data were collected at baseline, immediately after completion and at 1 year post-training. Additionally, individual narrative interviews were conducted with 10 participants at 1 year post-training. RESULTS: At 1 year of completion, the majority of participants were in paid employment. Difficulties included unclear PSW roles. The qualitative analyses revealed the following categories: 'Evolving from the patient role despite experiencing effects or consequences of mental illness', 'Feeling welcome and being confronted with conflicting expectations', 'Helping others while being needy at the same time' and 'Doing something worthwhile and the fear of failure'. CONCLUSION: Clear role descriptions, well-defined expectations, team preparation, acknowledgement of vulnerabilities and institution-level support PSWs are important to safeguard both PSWs and service users by minimising the destabilisation risk. Future EX-IN training graduates can benefit from the establishment of remunerated PSW roles in psychiatric services. PMID- 26801071 TI - Apigenin and naringenin regulate glucose and lipid metabolism, and ameliorate vascular dysfunction in type 2 diabetic rats. AB - Vascular endothelial dysfunction is regarded as the initial step of vascular complications in diabetes mellitus. This study investigated the amelioration of apigenin and naringenin in type 2 diabetic (T2D) rats induced by high-fat diet and streptozotocin and explored the underlying mechanism. Apigenin or naringenin was intragastrically administered at 50 or 100mg/kg once a day for 6 weeks. Biochemical parameters including blood glucose, glycated serum protein, serum lipid, insulin, superoxide dismutase (SOD), malonaldehyde and intercellular adhesion molecule-1 (ICAM-1) were measured. Vascular reactivity in isolated thoracic aortic rings was examined. Pathological features of the thoracic aorta were further observed through optical microscopy and transmission electron microscopy. Lastly, we evaluated their effects on insulin resistance of palmitic acid (PA)-induced endothelial cells. Compared with diabetic control group, apigenin and naringenin significantly decreased the levels of blood glucose, serum lipid, malonaldehyde, ICAM-1 and insulin resistance index, increased SOD activity and improved impaired glucose tolerance. Apigenin and naringenin restored phenylephrine-mediated contractions and acetylcholine or insulin-induced relaxations in aortic tissues. Furthermore, pathological damage in the thoracic aorta of apigenin and naringenin groups was more remissive than diabetic control group. In vitro, apigenin and naringenin inhibited NF-kappaB activation and ICAM 1 mRNA expression in PA-treated endothelial cells and improved nitric oxide production in the presence of insulin. In conclusion, both apigenin and naringenin can ameliorate glucose and lipid metabolism, as well as endothelial dysfunction in T2D rats at least in part by down-regulating oxidative stress and inflammation. In general, apigenin showed greater potency than naringenin equivalent. PMID- 26801070 TI - Clinical Validation and Implementation of a Targeted Next-Generation Sequencing Assay to Detect Somatic Variants in Non-Small Cell Lung, Melanoma, and Gastrointestinal Malignancies. AB - We tested and clinically validated a targeted next-generation sequencing (NGS) mutation panel using 80 formalin-fixed, paraffin-embedded (FFPE) tumor samples. Forty non-small cell lung carcinoma (NSCLC), 30 melanoma, and 30 gastrointestinal (12 colonic, 10 gastric, and 8 pancreatic adenocarcinoma) FFPE samples were selected from laboratory archives. After appropriate specimen and nucleic acid quality control, 80 NGS libraries were prepared using the Illumina TruSight tumor (TST) kit and sequenced on the Illumina MiSeq. Sequence alignment, variant calling, and sequencing quality control were performed using vendor software and laboratory-developed analysis workflows. TST generated >=500* coverage for 98.4% of the 13,952 targeted bases. Reproducible and accurate variant calling was achieved at >=5% variant allele frequency with 8 to 12 multiplexed samples per MiSeq flow cell. TST detected 112 variants overall, and confirmed all known single-nucleotide variants (n = 27), deletions (n = 5), insertions (n = 3), and multinucleotide variants (n = 3). TST detected at least one variant in 85.0% (68/80), and two or more variants in 36.2% (29/80), of samples. TP53 was the most frequently mutated gene in NSCLC (13 variants; 13/32 samples), gastrointestinal malignancies (15 variants; 13/25 samples), and overall (30 variants; 28/80 samples). BRAF mutations were most common in melanoma (nine variants; 9/23 samples). Clinically relevant NGS data can be obtained from routine clinical FFPE solid tumor specimens using TST, benchtop instruments, and vendor-supplied bioinformatics pipelines. PMID- 26801073 TI - The impact of occupation according to income on depressive symptoms in South Korean individuals: Findings from the Korean Welfare Panel Study. AB - BACKGROUND: In South Korea, societal perceptions on occupation are distinct, with people favouring white collar jobs. Hence both occupation type and income can have mental health effects. AIM: To examine the relationship between occupational classification and depression, along with the combined effect of occupational classification and household income. METHODS: Data were from the Korean Welfare Panel Study (KOWEPS), 2010-2013. A total of 4,694 economically active participants at baseline were followed. Association between occupational classification and depression, measured using the Center for Epidemiological Studies Depression (CES-D) scale 11, was investigated using the linear mixed effects model. RESULTS: Blue collar (beta: 0.3871, p = .0109) and sales and service worker groups (beta: 0.3418, p = .0307) showed higher depression scores than the white collar group. Compared to the white collar high-income group, white collar low income, blue collar middle income, blue collar middle-low income, blue collar low income, sales and service middle-high income, sales and service middle-low income and sales and service low-income groups had higher depression scores. CONCLUSION: Occupational classification is associated with increasing depression scores. Excluding the highest income group, blue collar and sales and service worker groups exhibit higher depression scores than their white collar counterparts, implying the importance of addressing these groups. PMID- 26801074 TI - Cardiovascular assessment in girls and women with Turner syndrome: a survey of current practice in the UK. PMID- 26801075 TI - Moral distress within neonatal and paediatric intensive care units: a systematic review. AB - OBJECTIVE: To review the literature on moral distress experienced by nursing and medical professionals within neonatal intensive care units (NICUs) and paediatric intensive care units (PICUs). DESIGN: Pubmed, EBSCO (Academic Search Complete, CINAHL and Medline) and Scopus were searched using the terms neonat*, infant*, pediatric*, prematur* or preterm AND (moral distress OR moral responsibility OR moral dilemma OR conscience OR ethical confrontation) AND intensive care. RESULTS: 13 studies on moral distress published between January 1985 and March 2015 met our inclusion criteria. Fewer than half of those studies (6) were multidisciplinary, with a predominance of nursing staff responses across all studies. The most common themes identified were overly 'burdensome' and disproportionate use of technology perceived not to be in a patient's best interest, and powerlessness to act. Concepts of moral distress are expressed differently within nursing and medical literature. In nursing literature, nurses are often portrayed as victims, with physicians seen as the perpetrators instigating 'aggressive care'. Within medical literature moral distress is described in terms of dilemmas or ethical confrontations. CONCLUSIONS: Moral distress affects the care of patients in the NICU and PICU. Empirical data on multidisciplinary populations remain sparse, with inconsistent definitions and predominantly small sample sizes limiting generalisability of studies. Longitudinal data reflecting the views of all stakeholders, including parents, are required. PMID- 26801076 TI - Presynaptic P2X1-3 and alpha3-containing nicotinic receptors assemble into functionally interacting ion channels in the rat hippocampus. AB - Previous studies documented a cross-talk between purinergic P2X (P2XR) and nicotinic acetylcholine receptors (nAChR) in heterologous expression systems and peripheral preparations. We now investigated if this occurred in native brain preparations and probed its physiological function. We found that P2XR and nAChR were enriched in hippocampal terminals, where both P2X1-3R and alpha3, but not alpha4, nAChR subunits were located in the active zone and in dopamine-beta hydroxylase-positive hippocampal terminals. Notably, P2XR ligands displaced nAChR binding and nAChR ligands displaced P2XR binding to hippocampal synaptosomes. In addition, a negative P2XR/nAChR cross-talk was observed in the control of the evoked release of noradrenaline from rat hippocampal synaptosomes, characterized by a less-than-additive facilitatory effect upon co-activation of both receptors. This activity-dependent cross-inhibition was confirmed in Xenopus oocytes transfected with P2X1-3Rs and alpha3beta2 (but not alpha4beta2) nAChR. Besides, P2X2 co-immunoprecipitated alpha3beta2 (but not alpha4beta2) nAChR, both in HEK cells and rat hippocampal membranes indicating that this functional interaction is supported by a physical association between P2XR and nAChR. Moreover, eliminating extracellular ATP with apyrase in hippocampal slices promoted the inhibitory effect of the nAChR antagonist tubocurarine on noradrenaline release induced by high- but not low-frequency stimulation. Overall, these results provide integrated biochemical, pharmacological and functional evidence showing that P2X1-3R and alpha3beta2 nAChR are physically and functionally interconnected at the presynaptic level to control excessive noradrenergic terminal activation upon intense synaptic firing in the hippocampus. PMID- 26801077 TI - Fumaric acid esters promote neuronal survival upon ischemic stress through activation of the Nrf2 but not HIF-1 signaling pathway. AB - Oxidative stress is a hallmark of ischemic stroke pathogenesis causing neuronal malfunction and cell death. Up-regulation of anti-oxidative genes through activation of the NF-E2-related transcription factor 2 (Nrf2) is one of the key mechanisms in cellular defense against oxidative stress. Fumaric acid esters (FAEs) represent a class of anti-oxidative and anti-inflammatory molecules that are already in clinical use for multiple sclerosis therapy. Purpose of this study was to investigate whether FAEs promote neuronal survival upon ischemia, and analyze putative underlying molecular mechanisms in neurons. Murine organotypic hippocampal slice cultures, and two neuronal cell lines were treated with dimethyl fumarate (DMF) and monomethyl fumarate (MMF). Ischemic conditions were generated by exposing cells and slice cultures to oxygen-glucose deprivation (OGD), and cell death was determined through propidium iodide staining. Treatment with both DMF and MMF immediately after OGD during reoxygenation strongly reduced cell death in hippocampal cultures ex vivo. Both DMF and MMF promoted neuronal survival in HT-22 and SH-SY5Y cell lines exposed to ischemic stress. DMF but not MMF activated the anti-oxidative Nrf2 pathway in neurons. Accordingly, Nrf2 knockdown in murine neurons abrogated the protective effect of DMF but not MMF. Moreover, FAEs did not activate the hypoxia-inducible factor (HIF) pathway suggesting that this pathway may not significantly contribute to FAE mediated neuroprotection. Our results may provide the basis for a new therapeutic approach to treat ischemic pathologies such as stroke with a drug that already has a broad safety record in humans. PMID- 26801078 TI - The needs, models of care, interventions and outcomes of palliative care in the Caribbean: a systematic review of the evidence. AB - BACKGROUND: Palliative care provision is expanding in low and middle income countries. Services are developing in the Caribbean in response to the region's ageing population, the significant burden of cancer, non-communicable diseases and HIV/AIDS. Appraisal of the existing evidence on palliative care needs, models of care, interventions and outcomes in the Caribbean is essential to inform emerging practice and future research. METHODS: Systematic review and narrative synthesis. Following implementation of a search strategy, titles, abstracts and full texts were screened. Data from nine studies were synthesized. The Qualsyst tools were used to assess the quality of quantitative and qualitative studies. Data were extracted into a common table, and themes were generated from the available peer review evidence using narrative synthesis. RESULTS: Nine papers were retained for appraisal. Eight papers described palliative care needs in the Caribbean. The needs for analgesia, support for patients, education and training of staff in palliative care and palliative care services were identified in the literature. Models of care for palliative care in the Caribbean were not described in great depth (n = 2 papers) and no intervention studies were found. Outcomes of palliative care such as quality of life, quality of care, and patient's preferred place of care and death were identified from six papers. Quantitative methodology was used in seven of the nine papers in this review. One paper used a mixed methodology design, and one a qualitative approach. CONCLUSIONS: Research from the Caribbean highlights the need for health care policy, training of staff, education, and access to analgesia and palliative care support services in this region. This sparse evidence must be taken into consideration with cultural beliefs and preferences of the Caribbean population in order to achieve improved outcomes for patients, their caregivers and health care professionals. This underscores the importance for more research in the field of palliative care in the Caribbean. PMID- 26801079 TI - Primary pancreatic paraganglioma: a case report and literature review. AB - BACKGROUD: Primary pancreatic paraganglioma is an extremely rare extra-adrenal paraganglioma. CASE PRESENTATION: We report a case of primary pancreatic paraganglioma undergoing middle segment pancreatectomy in a 42-year-old woman. Histological examination showed that the tumor was composed of well-defined nests of cuboidal cells separated by vascular fibrous septa, forming the classic Zellballen pattern. The chief cells showed positive staining to neuron-specific enolase, chromogranin A, synaptophysin, and the chief cells were surrounded by S 100 protein-positive sustentacular cells. The patient has remained tumor free for 12 months after surgery. A brief discussion about the histopathological features, clinical behavior, and treatment of primary pancreatic paraganglioma, and review of the relevant literature is presented. CONCLUSIONS: Primary pancreatic paraganglioma is a rare clinical entity, its diagnosis mainly depends on histopathological and immunohistochemical examinations. Complete surgical resection is the first choice of treatment and close postoperative follow-up is necessnary. PMID- 26801080 TI - Monotherapy with minocycline or trimethoprim/sulfamethoxazole for treatment of Stenotrophomonas maltophilia infections. AB - OBJECTIVES: Stenotrophomonas maltophilia is a Gram-negative bacillus intermittently isolated from hospitalized patients. Trimethoprim/sulfamethoxazole is considered the treatment of choice for S. maltophilia infections, though limited by toxicities. Minocycline is utilized at our institution for S. maltophilia infections due to its improved tolerability and in vitro susceptibility rates. Our objective was to evaluate the effectiveness of minocycline monotherapy compared with trimethoprim/sulfamethoxazole monotherapy for treatment of S. maltophilia infections. METHODS: Patients were identified via microbiology laboratory data and those with at least one positive culture for S. maltophilia were cross-referenced with pharmacy data to detect patients who received trimethoprim/sulfamethoxazole or minocycline. Patients initially receiving combination therapy were excluded. Our primary outcome was treatment failure, defined as receipt of alternative antibiotics with in vitro activity against S. maltophilia, isolation of S. maltophilia on repeat culture or death within 30 days of treatment. RESULTS: Forty-five patients were evaluated. Overall mortality rate was 9% and equal between groups; 41% of patients (9/22) who received trimethoprim/sulfamethoxazole and 30% (7/23) of patients who received minocycline experienced treatment failure (P = 0.67). Patients who received minocycline were more likely to have had a recent acute kidney injury (AKI) (43.5% versus 9%; P = 0.017) or chronic lung disease (52% versus 9%; P = 0.003). Logistic regression showed consistent results of non-inferiority of the primary outcome when controlling for rates of underlying lung pathology and recent AKI (P = 0.728). CONCLUSIONS: Treatment failure did not differ between patients receiving trimethoprim/sulfamethoxazole or minocycline monotherapy for treatment of S. maltophilia infections. PMID- 26801081 TI - Drug resistance mechanisms and their regulation in non-albicans Candida species. AB - Fungal pathogens use various mechanisms to survive exposure to drugs. Prolonged treatment very often leads to the stepwise acquisition of resistance. The limited number of antifungal therapeutics and their mostly fungistatic rather than fungicidal character facilitates selection of resistant strains. These are able to cope with cytotoxic molecules by acquisition of appropriate mutations, re wiring gene expression and metabolic adjustments. Recent evidence points to the paramount importance of the permeability barrier and cell wall integrity in the process of adaptation to high drug concentrations. Molecular details of basal and acquired drug resistance are best characterized in the most frequent human fungal pathogen, Candida albicans Effector genes directly related to the acquisition of elevated tolerance of this species to azole and echinocandin drugs are well described. The emergence of high-level drug resistance against intrinsically lower susceptibility to azoles in yeast species other than C. albicans is, however, of particular concern. This is due to their steadily increasing contribution to high mortality rates associated with disseminated infections. Recent findings concerning underlying mechanisms associated with elevated drug resistance suggest a link to cell wall and plasma membrane metabolism in non albicans Candida species. PMID- 26801082 TI - Pristinamycin in the treatment of MSSA bone and joint infection. AB - OBJECTIVES: The aim of this study was to evaluate pristinamycin in the treatment of MSSA bone and joint infection (BJI). PATIENTS AND METHODS: A retrospective, single-centre cohort study (2001-11) investigated outcome in adults receiving pristinamycin for MSSA BJI and pristinamycin-related adverse events (AEs). RESULTS: One hundred and two MSSA BJIs were assessed in 98 patients [chronic infection, 33.3%; and orthopaedic device-related infection (ODI), 67.6%]. Surgery was performed in 77.5% of total cases, and in all but three ODIs, associated with antibiotic therapy of a median total duration of 29.2 weeks. Pristinamycin was prescribed as a part of the initial intensive treatment phase (29.4%) and/or included in final maintenance therapy (83.3%) at a dose of 47.6 (45.5-52.6) mg/kg/day for 9.3 (1.4-20.4) weeks. AEs occurred in 13.3% of patients, consisting of gastrointestinal disorder (76.9%) or allergic reaction (23.1%), leading to treatment interruption in 11 cases. AEs were related to daily dose (OR, 2.733 for each 10 additional mg/kg/day; P = 0.049). After a follow-up of 76.4 (29.6-146.9) weeks, the failure rate was 34.3%, associated with ODI (OR, 4.421; P = 0.006), particularly when the implant was retained (OR, 4.217; P = 0.007). In most patients, the pristinamycin companion drug was a fluoroquinolone (68.7%) or rifampicin (21.7%), without difference regarding outcome. CONCLUSIONS: Pristinamycin is an effective, well-tolerated alternative therapeutic option in MSSA BJI, on condition that a daily dosage of 50 mg/kg is respected. PMID- 26801083 TI - Propensity score to detect baseline imbalance in cluster randomized trials: the role of the c-statistic. AB - BACKGROUND: Despite randomization, baseline imbalance and confounding bias may occur in cluster randomized trials (CRTs). Covariate imbalance may jeopardize the validity of statistical inferences if they occur on prognostic factors. Thus, the diagnosis of a such imbalance is essential to adjust statistical analysis if required. METHODS: We developed a tool based on the c-statistic of the propensity score (PS) model to detect global baseline covariate imbalance in CRTs and assess the risk of confounding bias. We performed a simulation study to assess the performance of the proposed tool and applied this method to analyze the data from 2 published CRTs. RESULTS: The proposed method had good performance for large sample sizes (n =500 per arm) and when the number of unbalanced covariates was not too small as compared with the total number of baseline covariates (>=40% of unbalanced covariates). We also provide a strategy for pre selection of the covariates needed to be included in the PS model to enhance imbalance detection. CONCLUSION: The proposed tool could be useful in deciding whether covariate adjustment is required before performing statistical analyses of CRTs. PMID- 26801084 TI - MOBP levels are regulated by Fyn kinase and affect the morphological differentiation of oligodendrocytes. AB - Oligodendrocytes are the myelinating glial cells of the central nervous system (CNS). Myelin is formed by extensive wrapping of oligodendroglial processes around axonal segments, which ultimately allows a rapid saltatory conduction of action potentials within the CNS and sustains neuronal health. The non-receptor tyrosine kinase Fyn is an important signaling molecule in oligodendrocytes. It controls the morphological differentiation of oligodendrocytes and is an integrator of axon-glial signaling cascades leading to localized synthesis of myelin basic protein (MBP), which is essential for myelin formation. The abundant myelin-associated oligodendrocytic basic protein (MOBP) resembles MBP in several aspects and has also been reported to be localized as mRNA and translated in the peripheral myelin compartment. The signals initiating local MOBP synthesis are so far unknown and the cellular function of MOBP remains elusive. Here, we show, by several approaches in cultured primary oligodendrocytes, that MOBP synthesis is stimulated by Fyn activity. Moreover, we reveal a new function for MOBP in oligodendroglial morphological differentiation. PMID- 26801085 TI - Degradation of aggregated LDL occurs in complex extracellular sub-compartments of the lysosomal synapse. AB - Monocyte-derived cells use an extracellular, acidic, lytic compartment (a lysosomal synapse) for initial degradation of large objects or species bound to the extracellular matrix. Akin to osteoclast degradation of bone, extracellular catabolism is used by macrophages to degrade aggregates of low density lipoprotein (LDL) similar to those encountered during atherogenesis. However, unlike osteoclast catabolism, the lysosomal synapse is a highly dynamic and intricate structure. In this study, we use high resolution three dimensional imaging to visualize compartments formed by macrophages to catabolize aggregated LDL. We show that these compartments are topologically complex, have a convoluted structure and contain sub-regions that are acidified. These sub-regions are characterized by a close apposition of the macrophage plasma membrane and aggregates of LDL that are still connected to the extracellular space. Compartment formation is dependent on local actin polymerization. However, once formed, compartments are able to maintain a pH gradient when actin is depolymerized. These observations explain how compartments are able to maintain a proton gradient while remaining outside the boundaries of the plasma membrane. PMID- 26801086 TI - Novel cell-penetrating peptide-adaptors effect intracellular delivery and endosomal escape of protein cargos. AB - The use of cell-penetrating peptides (CPPs) as biomolecular delivery vehicles holds great promise for therapeutic and other applications, but development has been stymied by poor delivery and lack of endosomal escape. We have developed a CPP-adaptor system capable of efficient intracellular delivery and endosomal escape of user-defined protein cargos. The cell-penetrating sequence of HIV transactivator of transcription was fused to calmodulin, which binds with subnanomolar affinity to proteins containing a calmodulin binding site. Our strategy has tremendous advantage over prior CPP technologies because it utilizes high-affinity non-covalent, but reversible coupling between CPP and cargo. Three different cargo proteins fused to a calmodulin binding sequence were delivered to the cytoplasm of eukaryotic cells and released, demonstrating the feasibility of numerous applications in living cells including alteration of signaling pathways and gene expression. PMID- 26801087 TI - Salient beliefs towards vaginal delivery in pregnant women: A qualitative study from Iran. AB - BACKGROUND: Childbirth by cesarean section has increased at an alarming rate over the past few years in Iran. The present study was designed to explore pregnant women's beliefs about the mode of delivery in order to provide some suggestions for future interventions to increase vaginal delivery. METHODS: This was a qualitative study framed by the Theory of Planned Behavior conducted in Tehran, Iran in 2013. Pregnant women attending public hospitals were recruited. The data were collected via in-depth interviews and focus group discussions. Interviews were conducted in a semi-structured manner. All interviews were tape recorded and transcribed verbatim. A content analysis approach was used to explore the data. RESULTS: In all 36 pregnant women participated in the study. The mean age of women was 27.8 (SD = 4.5) years. In general, women preferred vaginal delivery. During interviews and focus group discussions several themes emerged related to the pain associated with vaginal delivery, fears of childbirth, related health concerns, and the role of decision makers. The findings were grouped into three main themes namely: behavioral beliefs (negative and positive beliefs towards outcomes of vaginal delivery), normative beliefs (injunctive norms and descriptive norms), and control beliefs (internal and external barriers). CONCLUSION: Despite the fact that there were positive beliefs regarding vaginal delivery, participants indicated concerns related to loss of control and fear. It is essential that health care providers realize the psychological needs of women during pregnancy and the need for continuous support during childbirth. This type of support may improve their self-control during labor, and decrease fear of childbirth. PMID- 26801088 TI - Wound drains in posterior spinal surgery: a meta-analysis. AB - BACKGROUND: The use of drains following posterior spinal surgery is controversial. Thus, the aim of this meta-analysis was to review the advantages and adverse effects of closed suction drainage systems in posterior spinal surgery. METHODS: All randomized and non-randomized controlled trials comparing the use of closed suction drainage with no drainage in posterior spinal surgery were sought in PubMed, Medicine, Embase, and other Internet databases. All of the literature was searched and assessed by two independent reviewers, according to the standards of Cochrane systematic reviews. Data on functional and radiological outcomes in the two groups were pooled, which were then analyzed with RevMan software, version 5.2. RESULTS: Four randomized controlled trials (RCTs) and four non-RCTs met the inclusion criteria. Meta-analysis revealed that no significant differences were found regarding wound infection (P = 0.83), hematoma (P = 0.48), neurological injury (P = 0.21), estimated blood loss (P = 0.59), or dry and moderate dressing drainage between the groups. The number of patients with saturated dressings was larger in the no drainage group (P = 0.002). CONCLUSIONS: There is no obvious evidence to support the application of closed suction drains for posterior spinal surgery. Because of the limited quality of the evidence currently available, more high-quality RCTs with better experimental designs and larger patient samples should be performed. PMID- 26801089 TI - Stress granules and RNA processing bodies are novel autoantibody targets in systemic sclerosis. AB - BACKGROUND: Autoantibody profiles represent important patient stratification markers in systemic sclerosis (SSc). Here, we performed serum immunoprecipitations with patient antibodies followed by mass spectrometry (LC MS/MS) to obtain an unbiased view of all possible autoantibody targets and their associated molecular complexes recognized by SSc. METHODS: HeLa whole cell lysates were immunoprecipitated (IP) using sera of patients with SSc clinically positive for autoantibodies against RNA polymerase III (RNAP3), topoisomerase 1 (TOP1), and centromere proteins (CENP). IP eluates were then analyzed by LC-MS/MS to identify novel proteins and complexes targeted in SSc. Target proteins were examined using a functional interaction network to identify major macromolecular complexes, with direct targets validated by IP-Western blots and immunofluorescence. RESULTS: A wide range of peptides were detected across patients in each clinical autoantibody group. Each group contained peptides representing a broad spectrum of proteins in large macromolecular complexes, with significant overlap between groups. Network analyses revealed significant enrichment for proteins in RNA processing bodies (PB) and cytosolic stress granules (SG) across all SSc subtypes, which were confirmed by both Western blot and immunofluorescence. CONCLUSIONS: While strong reactivity was observed against major SSc autoantigens, such as RNAP3 and TOP1, there was overlap between groups with widespread reactivity seen against multiple proteins. Identification of PB and SG as major targets of the humoral immune response represents a novel SSc autoantigen and suggests a model in which a combination of chronic and acute cellular stresses result in aberrant cell death, leading to autoantibody generation directed against macromolecular nucleic acid-protein complexes. PMID- 26801090 TI - Physical activity guidelines and cardiovascular risk in children: a cross sectional analysis to determine whether 60 minutes is enough. AB - BACKGROUND: Physical activity reduces cardiovascular mortality and morbidity. The World Health Organisation (WHO) recommends children engage in 60 min daily moderate-to-vigorous physical activity (MVPA). The effect of compliance with this recommendation on childhood cardiovascular risk has not been empirically tested. To evaluate whether achieving recommendations results in reduced composite cardiovascular risk score (CCVR) in children, and to examine if vigorous PA (VPA) has independent risk-reduction effects. METHODS: PA was measured using accelerometry in 182 children (9-11 years). Subjects were grouped according to achievement of 60 min daily MVPA (active) or not (inactive). CCVR was calculated (sum of z-scores: DXA body fat %, blood pressure, VO2peak, flow mediated dilation, left ventricular diastolic function; CVR score >= 1SD indicated 'higher risk'). The cohort was further split into quintiles for VPA and odds ratios (OR) calculated for each quintile. RESULTS: Active children (92 (53 boys)) undertook more MVPA (38 +/- 11 min, P < 0.001), had greater VO2peak (4.5 +/- 0.8 ml/kg/min P < 0.001), and lower fat % (3.9 +/- 1.1 %, P < 0.001) than inactive. No difference were observed between active and inactive for CCVR or OR (P > 0.05). CCVR in the lowest VPA quintile was significantly greater than the highest quintile (3.9 +/- 0.6, P < 0.05), and the OR was 4.7 times higher. CONCLUSION: Achievement of current guidelines has positive effects on body composition and cardiorespiratory fitness, but not CCVR. Vigorous physical activity appears to have beneficial effects on CVD risk, independent of moderate PA, implying a more prescriptive approach may be needed for future VPA guidelines. PMID- 26801091 TI - Watch what happens: using a web-based multimedia platform to enhance intraoperative learning and development of clinical reasoning. AB - BACKGROUND: We aim to determine whether observed operations or internet-based video review predict improved performance in the surgery clerkship. METHODS: A retrospective review of students' usage of surgical videos, observed operations, evaluations, and examination scores were used to construct an exploratory principal component analysis. Multivariate regression was used to determine factors predictive of clerkship performance. RESULTS: Case log data for 231 students revealed a median of 25 observed cases. Students accessed the web-based video platform a median of 15 times. Principal component analysis yielded 4 factors contributing 74% of the variability with a Kaiser-Meyer-Olkin coefficient of .83. Multivariate regression predicted shelf score (P < .0001), internal clinical skills examination score (P < .0001), subjective evaluations (P < .001), and video website utilization (P < .001) but not observed cases to be significantly associated with overall performance. CONCLUSIONS: Utilization of a web-based operative video platform during a surgical clerkship is an independently associated with improved clinical reasoning, fund of knowledge, and overall evaluation. Thus, this modality can serve as a useful adjunct to live observation. PMID- 26801092 TI - Role confusion and self-assessment in interprofessional trauma teams. AB - BACKGROUND: Trauma care requires coordinating an interprofessional team, with formative feedback on teamwork skills. We hypothesized nurses and surgeons have different perceptions regarding roles during resuscitation; that nurses' teamwork self-assessment differs from experts', and that video debriefing might improve accuracy of self-assessment. METHODS: Trauma nurses and surgeons were surveyed regarding resuscitation responsibilities. Subsequently, nurses joined interprofessional teams in simulated trauma resuscitations. After each resuscitation, nurses and teamwork experts independently scored teamwork (T NOTECHS). After video debriefing, nurses repeated T-NOTECHS self-assessment. RESULTS: Nurses and surgeons assumed significantly more responsibility by their own profession for 71% of resuscitation tasks. Nurses' overall T-NOTECHS ratings were slightly higher than experts'. This was evident in all T-NOTECHS subdomains except "leadership," but despite statistical significance the difference was small and clinically irrelevant. Video debriefing did not improve the accuracy of self-assessment. CONCLUSIONS: Nurses and physicians demonstrated discordant perceptions of responsibilities. Nurses' self-assessment of teamwork was statistically, but not clinically significantly, higher than experts' in all domains except physician leadership. PMID- 26801093 TI - Global analysis of human duplicated genes reveals the relative importance of whole-genome duplicates originated in the early vertebrate evolution. AB - BACKGROUND: Gene duplication is a genetic mutation that creates functionally redundant gene copies that are initially relieved from selective pressures and may adapt themselves to new functions with time. The levels of gene duplication may vary from small-scale duplication (SSD) to whole genome duplication (WGD). Studies with yeast revealed ample differences between these duplicates: Yeast WGD pairs were functionally more similar, less divergent in subcellular localization and contained a lesser proportion of essential genes. In this study, we explored the differences in evolutionary genomic properties of human SSD and WGD genes, with the identifiable human duplicates coming from the two rounds of whole genome duplication occurred early in vertebrate evolution. RESULTS: We observed that these two groups of duplicates were also dissimilar in terms of their evolutionary and genomic properties. But interestingly, this is not like the same observed in yeast. The human WGDs were found to be functionally less similar, diverge more in subcellular level and contain a higher proportion of essential genes than the SSDs, all of which are opposite from yeast. Additionally, we explored that human WGDs were more divergent in their gene expression profile, have higher multifunctionality and are more often associated with disease, and are evolutionarily more conserved than human SSDs. CONCLUSIONS: Our study suggests that human WGD duplicates are more divergent and entails the adaptation of WGDs to novel and important functions that consequently lead to their evolutionary conservation in the course of evolution. PMID- 26801094 TI - Cognitive changes associated with switching to frequent nocturnal hemodialysis or renal transplantation. AB - BACKGROUND: It is uncertain whether switching to frequent nocturnal hemodialysis improves cognitive function in well-dialyzed patients and how this compares to patients who receive a kidney transplant. METHODS: We conducted a multicenter observational study with longitudinal follow-up of the effect on cognitive performance of switching dialysis treatment modality from conventional thrice weekly hemodialysis to frequent nocturnal hemodialysis, a functioning renal transplant or remaining on thrice-weekly conventional hemodialysis. Neuropsychological tests of memory, attention, psychomotor processing speed, executive function and fluency as well as measures of solute clearance were performed at baseline and again after switching modality. The change in cognitive performance measured by neuropsychological tests assessing multiple cognitive domains at baseline, 4 and 12 months after switching dialysis modality were analyzed using a linear mixed model. RESULTS: Seventy-seven patients were enrolled; 21 of these 77 patients were recruited from the randomized Frequent Hemodialysis Network (FHN) Nocturnal Trial. Of these, 18 patients started frequent nocturnal hemodialysis, 28 patients received a kidney transplant and 31 patients remained on conventional thrice-weekly hemodialysis. Forty-eight patients (62 %) returned for the 12-month follow-up. Despite a significant improvement in solute clearance, 12 months treatment with frequent nocturnal hemodialysis was not associated with substantial improvement in cognitive performance. By contrast, renal transplantation, which led to near normalization of solute clearance was associated with clinically relevant and significant improvements in verbal learning and memory with a trend towards improvements in psychomotor processing speed. Cognitive performance in patients on conventional hemodialysis remained stable with the exception of an improvement in psychomotor processing speed and a decline in verbal fluency. CONCLUSIONS: In patients on conventional thrice-weekly hemodialysis, receiving a functioning renal transplant was associated with improvement in auditory-verbal memory and psychomotor processing speed, which was not observed after 12 months of frequent nocturnal hemodialysis. PMID- 26801095 TI - The effects of immunomodulation by macrophage subsets on osteogenesis in vitro. AB - BACKGROUND: Bone formation and remodeling are influenced by the inflammatory state of the local microenvironment. In this regard, macrophages are postulated to play a crucial role in modulating osteogenesis. However, the differential effects of macrophage subsets and their plasticity on bone formation are currently unknown. METHODS: Polarized primary murine macrophages and preosteoblastic MC3T3 cells were co-cultured to investigate the effect of non activated M0, pro-inflammatory M1, and tissue-regenerative M2 macrophages on the osteogenic ability of MC3T3-E1 cells in vitro. Furthermore, to model the physiological transition from inflammation to tissue regeneration, M1-MC3T3 co cultures were treated with interleukin-4 (IL-4) at different time points to modulate the M1 phenotype towards M2. Macrophage phenotypic markers were assessed by flow cytometry and enzyme-linked immunosorbent assay. A time course study of osteogenic markers at different time points was conducted: alkaline phosphatase (ALP) mRNA levels were evaluated at week 1, ALP activity and osteocalcin and osteopontin mRNA levels at week 2, and matrix mineralization and osteocalcin and osteopontin protein concentrations at week 3. Supernatant collected 72 hours after seeding or IL-4 treatment, whichever was later, was analyzed for oncostatin M, a cytokine released by macrophages that has been recognized to enhance osteogenesis. Unpaired t test or one-way ANOVA with Tukey's or Dunnett's post hoc tests were used for statistical comparison of the groups. RESULTS: Co-culture with any of the macrophage subtypes increased the osteogenic ability of MC3T3 cells as indicated by increases in ALP activity and matrix mineralization. Increased ALP activity, osteocalcin concentration, and matrix mineralization demonstrated that osteogenesis by M1-MC3T3 co-cultures was further enhanced by macrophage phenotype modulation to M2 via IL-4 treatment 72 hours after seeding. Increased oncostatin M protein concentration in untreated M1-MC3T3 co-cultures and M1-MC3T3 co-cultures treated with IL-4 at 72 hours correlated with greater ALP activity and matrix mineralization. CONCLUSIONS: These results suggest that a transient inflammatory phase is crucial for enhanced bone formation. Macrophage plasticity may offer new strategies for modulating the local inflammatory microenvironment with the aim of potentially enhancing bone repair. PMID- 26801096 TI - Insulin-like growth factors are essential to prevent anoikis in oestrogen responsive breast cancer cells: importance of the type I IGF receptor and PI3 kinase/Akt pathway. AB - BACKGROUND: Detachment of epithelial cells from the extracellular matrix initiates programmed cell death by a process termed anoikis. Malignant cells must acquire anoikis resistance to leave the primary tumour and metastasise. Multiple signal transduction pathways can activate anoikis and confer anoikis resistance, but these are not understood in breast cancer. METHODS: Models for anoikis of oestrogen-responsive breast cancer cells were established and the protective effects of IGF-1 tested. Cleaved PARP was measured by western transfer and cleaved caspase 3 by flow cytometry. Pathways involved in anoikis and in anoikis resistance were investigated with PI3-kinase, Akt, and MEK1 and MEK2 inhibitors. The importance of the type I IGF receptor was investigated by IGF-concentration dependence, siRNA knockdown and pharmacological inhibition. Association between IGF-1R expression and relapse with distant metastasis was analysed in 1609 patients by log rank test. RESULTS: Unattached breast cancer cells required culture in serum-free medium to induce anoikis. Rapid loss of FAK, Akt and Bad phosphorylation was concurrent with anoiks induction, but ERK1 and ERK2 phosphorylation increased which suggested that anoikis resistance is mediated by the PI3-kinase/Akt rather than the Grb2/Ras/MAP-kinase pathway. IGF-1 conferred anoikis resistance in serum-free medium. IGF-1 activated the PI3-kinase/Akt and Grb2/Ras/MAP-kinase pathways but experiments with PI3-kinase, Akt and MEK1 and MEK2 inhibitors showed that IGF protection is via the PI3-kinase/Akt pathway. The concentration dependence of IGF protection, knockdown experiments with siRNA and pharmacological inhibition with figitumumab, showed that IGF-1 signals through the type I IGF receptor. The crucial role of the type I IGF receptor was demonstrated by induction of anoikis in full serum by figitumumab. High IGF-1R expression was associated with reduced time to relapse with distant metastases in oestrogen receptor-positive patients, especially those with aggressive disease which confirms its relevance in vivo. CONCLUSIONS: Anoikis resistance of oestrogen-responsive breast cancer cells depends upon IGF activation of the type I IGF receptor and PI3-kinase/Akt pathway. Because IGF-dependent evasion of anoikis will facilitate metastasis by malignant breast cancer cells, effective inhibition of IGF signal transduction should be included in combinations of targeted drugs designed to treat metastatic oestrogen receptor-positive breast cancers. PMID- 26801097 TI - Associations between lifestyle behaviours and optimal wellbeing in a diverse sample of New Zealand adults. AB - BACKGROUND: In positive psychology optimal wellbeing is considered a broad, multi dimensional construct encompassing both feelings and functioning. Yet, this notion of wellbeing has not been translated into public health. The purpose of this study is to integrate public health and positive psychology to determine associations between lifestyle behaviours and optimal wellbeing in a diverse sample of New Zealand adults. METHODS: A web-based survey design was employed to collect data. Participants reported on their wellbeing and lifestyle behaviours including nutrition, exercise, sedentary behaviour, and sleep. Optimal wellbeing was calculated using a multi-dimensional scale designed to mirror the internationally recognised diagnostic criteria for mental disorders. Binary logistic regression was used to calculate associations between 10 lifestyle behaviours and optimal wellbeing. RESULTS: Of the total sample (n = 9514), 24 % met the criteria for optimal wellbeing. Compared to reference groups, the association with optimal wellbeing was greater for those who reported exercising >= 7 times/week (odds ratio: 1.61, 95 % confidence interval: 1.22-2.13, p < 0.01) and sitting "almost none of the time" (1.87, 1.01-3.29, p < 0.01). Optimal wellbeing was lower for those reporting restless sleep "almost all of the time" (0.24, 95 % CI: 0.17-0.32 p < 0.01) and consuming sugary drinks 5-6 times/week (0.73, 95 % CI: 0.53-0.95, p < 0.05). CONCLUSIONS: Public health and positive psychology were integrated to provide support for a relationship between lifestyle behaviours and a multi-dimensional measure of optimal wellbeing. It is likely this relationship between lifestyle behaviours and optimal wellbeing is bidirectional giving rise to the debate that holistic approaches are needed to promote positive health. PMID- 26801099 TI - Isolation and characterization of hematopoietic stem cells in teleost fish. AB - Despite 400 million years of evolutionary divergence, hematopoiesis is highly conserved between mammals and teleost fish. All types of mature blood cells including the erythroid, myeloid, and lymphoid lineages show a high degree of similarity to their mammalian counterparts at the morphological and molecular level. Hematopoietic stem cells (HSCs) are cells that are capable of self-renewal and differentiating into all hematopoietic lineages over the lifetime of an organism. The study of HSCs has been facilitated through bone marrow transplantation experiments developed in the mouse model. In the last decade, the zebrafish and clonal ginbuna carp (Carassius auratus langsdorfii) have emerged as new models for the study of HSCs. This review highlights the recent progress and future prospects of studying HSCs in teleost fish. Transplantation assays using these teleost models have demonstrated the presence of HSCs in the kidney, which is the major hematopoietic organ in teleost fish. Moreover, it is possible to purify HSCs from the kidney utilizing fluorescent dyes or transgenic animals. These teleost models will provide novel insights into the universal mechanisms of HSC maintenance, homeostasis, and differentiation among vertebrates. PMID- 26801098 TI - Effects of exercise training on carotid intima-media thickness in patients with type 2 diabetes and coronary artery disease. Influence of carotid plaques. AB - BACKGROUND: Carotid intima-media thickness (cIMT) holds prognostic information for future cardiovascular disease and is associated with the extent of coronary atherosclerosis. We investigated the effect of exercise on cIMT progression in patients with both type 2 diabetes and coronary artery disease (CAD). METHODS: Patients with type 2 diabetes and CAD (n = 137) were randomized to exercise training or standard follow-up. The 12 month exercise program contained 150 min weekly of combined aerobic and resistance training. High-resolution ultrasonography of the distal part of the common carotid artery (CCA) was performed to measure cIMT before and after the intervention. The CCA and the carotid bulb were scanned for the presence of atherosclerotic plaques. Differences in changes between the randomized groups were calculated by one-way ANCOVA. RESULTS: In the total population no difference in changes of cIMT from baseline to 12 months was observed between the exercise group and controls [ 0.016 mm (95 % CI -0.037 to 0.006) vs. -0.007 mm (95 % CI -0.029 to 0.015), p = 0.57]. However, there was a significant interaction between the effect of exercise training and the presence of carotid plaques (p = 0.013), and significant reduced cIMT was demonstrated in the exercise group compared with controls in patients without identified carotid plaques (n = 65) [-0.034 mm (95 % CI -0.060 to 0.008) vs. 0.013 mm (95 % CI -0.011 to 0.038), p = 0.010]. CONCLUSION: One year of exercise training in patients with type 2 diabetes and CAD did not significantly change cIMT progression. However, in patients without identified carotid plaques, beneficial effect of exercise training on cIMT progression was demonstrated. PMID- 26801100 TI - Molecular characterization and function of a PTEN gene from Litopenaeus vannamei after Vibrio alginolyticus challenge. AB - PTEN, a tumor suppressor gene, suppresses cell survival, growth, apoptosis, cell migration and DNA damage repair by inhibiting the PI3K/AKT signaling pathway. In this study, the full-length Litopenaeus vannamei PTEN (LvPTEN) cDNA was obtained, containing a 5'UTR of 59bp, an ORF of 1269bp and a 3'UTR of 146bp besides the poly (A) tail. The PTEN gene encoded a protein of 422 amino acids with an estimated molecular mass of 48.3 KDa and a predicted isoelectric point (pI) of 7.6. Subcellular localization analysis revealed that LvPTEN was distributed in both cytoplasm and nucleus, and the tissue distribution patterns showed that LvPTEN was ubiquitously expressed in all the examined tissues. Vibrio alginolyticus challenge induced upregulation of LvPTEN expression. Moreover, RNAi knock-down of LvPTEN in vivo significantly increased the expression of LvAKT mRNA, while reducing that of the downstream apoptosis genes LvP53 and LvCaspase3. LvPTEN knock-down also caused a sharp increase in cumulative mortality, bacterial numbers, and DNA damage in the hemolymph of L. vannamei following V. alginolyticus challenge, together with a sharp decrease in the total hemocyte count (THC). These results suggested that LvPTEN may participate in apoptosis via the PI3K/AKT signaling pathway in L. vannamei, and play an important role in shrimp innate immunity. PMID- 26801101 TI - Characterization of cytological changes, IgA, IgG and IL-8 levels and pH value in the vagina of prepubertal and sexually mature Ellegaard Gottingen minipigs during an estrous cycle. AB - The pig is increasingly used as an advanced animal model of the genital tract in women and knowledge on the genital immune system is therefore needed. In this study, evaluation of vaginal smears revealed that almost no neutrophils or other leukocytes were present in the vaginal mucosa of prepubertal minipigs (n = 10). In sexually mature minipigs (n = 10), evaluated through an estrous cycle, there was an increase in number of mucosal neutrophils and other leukocytes during estrus. The level of total IgA on the vaginal mucosa increased during diestrus. The level of total IgG showed no significant changes through the cycle. The vaginal IgA level in the prepubertal minipigs was similar to the low estrus level in sexually mature minipigs, and the IgG level in prepubertal was similar to the stable level in the sexually mature minipigs. PMID- 26801102 TI - Flavonoids of Polygonum hydropiper L. attenuates lipopolysaccharide-induced inflammatory injury via suppressing phosphorylation in MAPKs pathways. AB - BACKGROUND: Polygonum hydropiper L. is widely used as a traditional remedy for the treatment of dysentery, gastroenteritis. It has been used to relieve swelling and pain, dispel wind and remove dampness, eliminate abundant phlegm and inflammatory for a long time. Previous study showed that antioxidants especially flavonoids pretreatment alleviated sepsis-induced injury in vitro and in vivo. In the present study, the possible anti-inflammatory effect of flavonoids from normal butanol fraction of Polygonum hydropiper L. extract (FNP) against inflammation induced by lipopolysaccharide (LPS) was evaluated in vivo and in vitro. METHODS: The content of total flavonoid of FNP was determined by the aluminum colorimetric method. The content of rutin, quercetin and quercitrin was determined by HPLC method. Mice received FNP orally 3 days before an intra peritoneal (i.p.) injection of lipopolysaccharide (LPS). Total superoxidase dismutase (T-SOD), total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX), glutathione (GSH), myeloperoxidase (MPO) and malondialdehyde (MDA) levels were measured. Tumor necrosis factor-alpha levels in serum and tissue was measured. mRNA expressions of pro-inflammatory cytokines in lung were assessed by Real-Time PCR. Histopathological changes were evaluated in lung, ileum and colon. We also investigated FNP on reactive oxygen species (ROS), nitric oxide (NO) and pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6 and IL-8) production, inducible nitric oxide synthase (iNOS), Cyclooxygenase-2 (COX-2) protein expression, phosphorylation of MAPKs and AMPK in LPS-stimulated RAW264.7 cells. RESULTS: FNP increased the levels of T-SOD, T-AOC, GSH-PX and GSH, decreased the levels of TNF-alpha, MPO and MDA, attenuate the histopathological lesion in LPS stimulated mice. FNP inhibited production of inflammatory cytokines, ROS and NO, protein expressions of iNOS and COX-2, phosphorylation of ERK, JNK and c-JUN in MAPKs, promoted phosphorylation of AMPKalpha suppressed by LPS. CONCLUSION: These results suggested in vivo anti-inflammatory activities of FNP might contributed to its enhancement in antioxidant capacity, its inhibitory effects may be mediated by inhibiting the phosphorylation of JNK, ERK and c-JUN in MAPKs signaling pathways. PMID- 26801103 TI - Acupuncture has a positive effect on asthmatic rats in a glucocorticoid independent manner. AB - BACKGROUND: There is some evidence to support the use of acupuncture as an alternative therapy for asthma. However, the mechanisms underlying its effects are not fully understood. We have reported previously that acupuncture has beneficial effects on asthma without changing the concentration of serum cortisol, although endogenous glucocorticoid (GC) plays an important role in regulating immune responses. OBJECTIVE: In this study, bilateral adrenalectomy (removal of both adrenal glands) was performed in rats before asthma model induction to investigate whether acupuncture influences asthma in a GC-dependent manner. METHODS: Adrenal-intact and adrenalectomised rats were injected with ovalbumin to induce asthma and then left untreated or treated with manual acupuncture (MA) at GV14, bilateral BL12 and bilateral BL13, or manual restraint without MA. Healthy and sham-adrenalectomised control groups were also included. Pulmonary resistance (RL), serum concentrations of corticosterone, and eosinophil counts were measured at the end of the experimental course. Sera from adrenal intact and adrenalectomised asthmatic rats treated with acupuncture were injected into untreated adrenal-intact and adrenalectomised asthmatic rats to investigate further the potential role of GC in the effect of acupuncture. RESULTS: Acupuncture significantly decreased RL and eosinophil count in both adrenal intact and adrenalectomised asthmatic rats. Moreover, administration of sera derived from acupuncture-treated adrenal-intact and adrenalectomised asthmatic rats attenuated the increase in RL and eosinophil count in both asthmatic models. CONCLUSIONS: Results of this study suggest that endogenous GC is not a key contributor to the effects of acupuncture on asthma, and that acupuncture may have potentially therapeutic effects on asthma in a GC-independent manner. PMID- 26801140 TI - Performance of Four Multivariate Tests Under Variance-Covariance Heteroscedasticity. AB - Type I error rates (tau) of four multivariate tests - Pillai-Bartlett trace, Johansen's test, James' first order test and James' second order test - were compared for heterogeneous covariance matrices. A total of 360 simulated experiments were conducted. Johansen's test and James' second order test performed better than the other two tests. The tau of Johansen's test should be very close to a when the ratio of total sample size to number of variables (N/p) is large, and the smaller samples are associated with covariance matrices with smaller elements. James' second order test outperformed the other tests under extreme conditions; that is, when Nip is small, the heterogeneity of covariance matrices is large, the sample size ratio is large, or the smaller samples are associated with covariance matrices with larger elements. PMID- 26801141 TI - General and Specific Abilities as Predictors of School Achievement. AB - The purpose of this study is to investigate the relations between aptitude variables and school achievement using a model of ability which allows simultaneous identification of general and specific abilities. A battery of 16 aptitude tests was administered in the 6th grade and course grades were collected in 17 different subject matter areas in the 9th grade (N = 866). For the aptitude tests a confirmatory factor model is fitted with a general factor (G) along with nine orthogonal, residual factors. Some of the residual factors are quite broad (Crystallized intelligence, Gc(1), and General visualization G(1)), but most are narrow factors identified by pairs of tests (e.g., V(1), Ms(1), Num Ach(1), Vz(1), S, and Cs(1)). A model is fitted to the 17 course grades as well. The model includes a general school achievement factor (GENACH) and domain specific achievement factors in areas such as science-mathematics (SCIENCE), social science (SOCSCI(1)), language (LANG(1)) and spatial-practical performance (SPATPR(1)). Relating the latent criterion variables to the latent aptitude variables it is found that some 40% of the variance in GENACH may be accounted for by G and Gc(1). However, larger proportions of variance are accounted for in the domain specific achievement factors and different aptitude factors are important in different domains. It is conclu~ded that differentiation among at least a limited number of broad abilities may be worthwhile. PMID- 26801142 TI - Care and Justice Moral Reasoning: A Multidimensional Scaling Approach. AB - In contrast to Kohlberg's (1969) universal model of moral development, Gilligan's (1982) model posits the existence of separate patterns of moral development for men and women. The pattern for men, termed the "justice ethic," is based on abstract concepts of justice, reciprocity, and individual rights. The pattern for women, termed the "care ethic," is based on responsibility toward others and the preservation of relationships. The purpose of this article is to utilize a recently developed multidimensional scaling methodology to explore the underlying structure of moral reasoning responses to 12 moral dilemmas, developed on the basis of Gilligan's theory, and to relate that structure to individual difference characteristics. Results of findings and implications for future research are discussed. PMID- 26801143 TI - Asymptomatic Independence and Separability in Convariance Structure Models: Implications for Specification Error, Power, and Model Modification. AB - This article presents a didactic discussion on the role of asymptotically independent test statistics and separable hypotheses as they pertain to issues of specification error, power, and model modification in the covariance structure modeling framework. Specifically, it is shown that when restricting two parameter estimates on the basis of the multivariate Wald test, the condition of asymptotic independence is necessary but not sufficient for the univariate Wald test statistics to sum to the multivariate Wald test. Instead, what is required is mutual asymptotic independence (MAI) among the univariate tests. This result generalizes to sets of multivariate tests as well. When MA1 is lacking, hypotheses can exhibit transitive relationships. It is also shown that the pattern of zero and non-zero elements of the covariance matrix of the estimates are indicative of mutually asymptotically independent test statistics, separable and transitive hypotheses. The concepts of MAI, separability, and transitivity serve as an explanatory framework for how specification errors are propagated through systems of equations and how power analyses are differentially affected by specification errors of the same magnitude. A small population study supports the major findings of this article. The question of univariate versus multivariate sequential model modification is also addressed. We argue that multivariate sequential model modification strategies do not take into account the typical lack of MA1 thus inadvertently misleading substantive investigators. Instead, a prudent approach favors univariate sequential model modification. PMID- 26801144 TI - Relative/Proportional Scoring of the Ways of Coping Checklist: Is it Advantageous or Artificial. AB - One way of scoring the Ways of Coping Checklist is to compute relative1 proportional scores in which the mean score for each scale is divided by the sum of the means for all of the scales. The proportional scoring method reportedly sets the score on each scale relative to the score for the whole scale. Using the proportional scores, direct comparisons can be made for the profiles of subjects who differ in term of the sheer magnitude of their responses. In the present article, it is argued that the relative scoring method introduces an artifact that confounds multivariate statistical analyses and ignores an individual's general reactivity to problems. Quantitative examples are given to illustrate some of the ways in which relative scoring distorts the pattern of intercorrelations among the WCC scales and thereby produces misleading multivariate results. Multivariate analysis of the raw scores is then shown to accomplish the mission set forth for the relative1 proportional scores. The latter analysis suggests that an intricate structural relationship exits between components of coping and depression. It is concluded that the relationship between coping and depression may be a matter of how effective the coping effort is when the individual is reactive to problems. PMID- 26801145 TI - Costs of Treatment of Chronic Obstructive Pulmonary Disease. AB - The aim of this study was to analyze direct costs of COPD therapy in relation with clinical course and stage of the disease. Sixty patients with moderate to severe COPD were included into the study. The average cost was taken from institutional data file and was also assessed from a social perspective. Results were presented as average costs per patient per year. Forty two percent of patients was classified as GOLD D category, while categories A, B, and C accounted for 8 %, 27 %, and 23 %, respectively. Approximately 65 % of patients had 2-3 degrees of dyspnea according to the Modified Medical Research Council Dyspnea Scale. About 60 % of patients underwent two or three exacerbations per year and those patients had one or two co-morbidities diagnosed. Treatment costs almost doubled with disease progression, mainly due to exacerbations. In patients in Group C and Group D with exacerbations the direct costs were several times higher than in group A or B and the difference increased with progression of the disease. In Groups A and B, the costs of treatment of stable disease or with exacerbation were comparable. We conclude that costs of treatment of COPD patients were highest in advanced disease and were strongly related to COPD exacerbations. PMID- 26801146 TI - Antibiotic Prescription Practices Among Children with Influenza. AB - The important factor in the development of resistance to antibiotics is their overuse, especially for viral respiratory infections. The aim of the study was to find out the frequency of the antibiotic therapy administrated to children with influenza. A total of 114 children younger than 59 months seeking care for the acute respiratory tract infection was enrolled into the study. The patients had influenza-like symptoms: fever > 38 degrees C, cough, and sore throat of less than 4 days duration. Nasal and pharyngeal swabs were tested for influenza A and B virus with a real-time PCR. Thirty six cases of influenza were diagnosed: 34 of influenza A (H3N2) and 2 of influenza B. The rate of influenza infection was 32 % in the study group. The antibiotic therapy was ordered for 58 % patients with influenza. Antibiotics were given less frequently in the outpatient setting (33 %) compared with the hospitalized patients (93 %) (p < 0.05). The most often administrated antibiotics were amoxicillin with clavulanic acid, cefuroxime, and amoxicillin. None of the patients received oseltamivir. Antibiotics were overused, while antivirals were underused among children with influenza. To improve health care quality, more efforts in the diagnosis of influenza and the appropriate use of antimicrobials and antivirals are required. PMID- 26801147 TI - Socioeconomic Effects of Chronic Obstructive Pulmonary Disease from the Public Payer's Perspective in Poland. AB - Chronic obstructive pulmonary disease (COPD) is currently the third most common cause of death worldwide and the total number of people affected reaches over 200 million. It is estimated that approximately 50 % of persons having COPD are not aware of it. In the EU, it is estimated that the total annual costs of COPD exceed ?140 billion, and the expected increase in the number of cases and deaths due to COPD would further enhance economic and social costs of the disease. In this article we present the results of cost analysis of health care benefits associated with the treatment of COPD and with the disease-related incapacity for work. The analysis is based on the data of the National Health Fund and the Social Insurance Institutions, public payers of health benefits in Poland. The annual 2012 expenditures incurred for COPD treatment was ?40 million, and the benefits associated with incapacity for work reached more than ?55 million. The extent of these expenditures indicates that it is necessary to optimize the functioning system, including the allocation of resources for prevention, social awareness, and detection of COPD at early stages when treatment costs are relatively low. PMID- 26801148 TI - The Role of Inspiratory Muscle Training in the Process of Rehabilitation of Patients with Chronic Obstructive Pulmonary Disease. AB - Chronic obstructive pulmonary disease (COPD) adversely affects the quality of life and life expectancy of patients. Shortness of breath, cough, and fatigue in lower limbs are the main reasons limiting physical activities of patients. The lack of physical activity results in poorer muscle strength. The latest guidelines regarding breathing rehabilitation in COPD patients emphasize a significant role of inspiratory muscle exercises. The objective of the present study was to evaluate the effects of an 8-week long inspiratory muscle training, interval training on a cycle ergometer, and training combining both kinds of rehabilitation, on pulmonary function, health-related quality of life, and the tolerance to exercise in patients with COPD. The study was conducted in a group of 43 patients with diagnosed COPD stage II and III according to GOLD. They were randomly divided into four training groups: inspiratory muscle training (Group 1), cycle ergometer training (Group 2), cycle ergometer and inspiratory muscle training (Group 3), control group - patients who did not participate in any rehabilitation programs (Group 4 - control). Before the rehabilitation process and after its completion the patients were medically examined, they completed a health-related quality of life questionnaire, performed a 6-min walk test, spirometry, and a treadmill exercise test according to the modified Bruce protocol. The results demonstrate a significant improvement in the quality of life measured for Group 3 in comparison with the control group. PMID- 26801149 TI - Polymorphism of FCGR2A, FCGR2C, and FCGR3B Genes in the Pathogenesis of Sarcoidosis. AB - We have previously presented evidence that the polymorphism of the FCGR3A gene, encoding the receptor for Fc fragment of immunoglobulin G IIIa (FcgammaRIIIa) plays a role in the enhancement of circulating immune complexes (CIs) with the occurrence of Mycobacterium tuberculosis heat shock proteins in patients with sarcoidosis (SA). The immunocomplexemia might be caused by decreased affinity of CIs to Fcgamma receptors, with the subsequently decreased receptor clearance by immune cells. In the present study we examined whether the polymorphisms of other related genes (FCGR2A, FCGR2C, FCGR3B) encoding other activatory Fcgamma receptors, could have a similar effect. To this end, we genotyped 124 patients with sarcoidosis and 148 healthy volunteers using polymerase chain reaction with sequence-specific primers. We revealed a significant decrease in the percentage of the FCGR2A and FCGR2C variants that ensure effective CIs clearance, with a concomitant increase of less functional variants of these genes in Stages I/II, compared with Stages III/IV of SA. There was no aberration in FCGR3B allele/genotype frequencies. We conclude that the FCGR2A and FCGR2C polymorphisms may also contribute to immunocomplexemia present in SA. The assessment of FCGR genes could become a tool in presaging a clinical course of sarcoidosis and in its personalized therapy. PMID- 26801150 TI - Growth, Nutritional Status, and Pulmonary Function in Children with Chronic Recurrent Bronchitis. AB - Bronchitis is a common health problem in children. Frequent bronchitis in infancy increases the risk of developing chronic respiratory diseases. The aim of the study was to assess the level of growth and the nutritional status in children and youths with special regard to the level of body fatness assessed by measuring skin-fold thickness. Relationships between somatic development, pulmonary function and the course of the disease were also explored. The study was carried out using anthropometric and spirometric measurements and also information on the severity and course of the disease in 141 children with chronic or recurrent bronchitis. All of the subjects were patients of the Pulmonary Medicine and Allergology Center in Karpacz, Poland. The mean body height did not differ significantly between the children examined and their healthy peers. However, the infection-prone children had excessive body fatness and muscle mass deficiency. The increased level of subcutaneous adipose tissue occurred especially in children with short duration of the disease, i.e. a maximum of 1 year. The functional lung parameters were generally normal. The presence of atopic diseases such as allergic rhinitis or atopic dermatitis did not impair the course of the children's somatic development. Also, long-term disease or the presence of additional allergic diseases did not impair lung function in the examined children. Taking appropriate preventive measures is recommended to achieve and maintain normal body weight in children who receive therapy due to bronchitis. PMID- 26801151 TI - Incidence and Clinical Course of Respiratory Viral Coinfections in Children Aged 0-59 Months. AB - Clinical data available on coinfections are contradictory concerning both the number of viruses involved and the severity of the condition. A total of 114 patients aged 0-59 months with symptoms of respiratory tract infection were enrolled into the study. Nasal and pharyngeal swabs were tested using the PCR method for the following 12 viruses: influenza A, influenza B, respiratory syncytial virus A (RSV A), respiratory syncytial virus B (RSV B), adenovirus, metapneumovirus, coronavirus 229E/NL63 (hCoV229), coronavirus OC43 (hCoVOC43), parainfluenza virus 1 (PIV-1), parainfluenza virus 2 (PIV-2), parainfluenza virus 3 (PIV-3), and rhinovirus A/B. Coinfections were detected in nine (8 %) patients. Five of the coinfections were related to influenza A (H3N2) virus associated with the following other, single or combined, respiratory viruses: influenza B in one case, hCoV229 in two cases, hCoV229, RSV A, and PIV-2 in one case, and PIV-1, PIV 2, RSV A, RSV B, and adenovirus in one case. The other four coinfections were caused by: adenovirus and hCoVOC43, adenovirus, and rhinovirus, RSV A and PIV-1, influenza B, and RSV B. We did not observe any significant differences in the clinical course of infections caused either by a single or multiple viral factors. PMID- 26801152 TI - Relationships Between Tobacco Abuse and Self-Assessment of Health. AB - Smoking cigarettes negatively influences the functioning of the body. Among other effects, it has an important impact on the respiratory system, circulation, and behavior. It leads to morphological and physiological changes in organs and tissues, so it can change mood. The aim of this study was to assess the relationships between tobacco abuse and self-assessment of health. The survey was conducted among Polish (243) and foreign (80) medical students at the Pomeranian Medical University in Szczecin, Poland. The study was based on a survey questionnaire of the authors' own design, comprising open and multi-choice questions. Our questionnaire was based on the international standard questionnaire from the Health Behavior in School-Aged Children study (Currie et al. 2009). 80 % of students surveyed were free of any chronic diseases. The results showed that only 23 % of the women and 20 % of the men assessed their health as very good, over 60 % as good, and the remaining at lower levels. We did not observe significant differences between smokers and non-smokers. Physical activity in both groups was generally assessed as good or sufficient. We did not observe significant differences between groups in the incidence of headache, abdominal pain, or vertigo. Significant differences were found in the intake of painkillers. PMID- 26801153 TI - Monitoring the effects of wastewater treatment strategies. AB - Wastewater disposal in coastal waters causes widespread environmental problems. Secondary treatment is expected to reduce the adverse effects of insufficiently treated wastewater. The environmental impact of sewage disposal via 18 wastewater treatment plants was analysed using the benthic opportunistic polychaetes and amphipods (BOPA) index. In previous studies this index proved to be an effective tool for monitoring sewage pollution. The impact of these discharges was highly related to treatment level, which ranged from pre-treatment to biological, as well as to flow rates and outfall position. Locations affected by pre-treated wastewater showed environmental degradation, especially marked near outfalls with higher flow rates. At most locations, biologically treated wastewater did not cause a significant impact and an improvement in ecological integrity was detected after this secondary treatment had been implemented. The impact of discharge was highly related to chemical oxygen demand (COD), suspended solids and nutrient concentrations, which are all lower in biologically treated wastewater. A 'moderate' ecological status was observed not only near sewage outfalls with high wastewater flow rates (>1,500,000 m(3)/month) with a COD over 200 mg/l but also near those with lower flow rates but with a COD over 400 mg/l. To reduce the impact of sewage disposal, it is necessary to carry out adequate treatment, have site outfalls deep enough, and implement water recycling. PMID- 26801154 TI - Quantifying in-stream retention of nitrate at catchment scales using a practical mass balance approach. AB - As field data on in-stream nitrate retention is scarce at catchment scales, this study aimed at quantifying net retention of nitrate within the entire river network of a fourth-order stream. For this purpose, a practical mass balance approach combined with a Lagrangian sampling scheme was applied and seasonally repeated to estimate daily in-stream net retention of nitrate for a 17.4 km long, agriculturally influenced, segment of the Steinlach River in southwestern Germany. This river segment represents approximately 70% of the length of the main stem and about 32% of the streambed area of the entire river network. Sampling days in spring and summer were biogeochemically more active than in autumn and winter. Results obtained for the main stem of Steinlach River were subsequently extrapolated to the stream network in the catchment. It was demonstrated that, for baseflow conditions in spring and summer, in-stream nitrate retention could sum up to a relevant term of the catchment's nitrogen balance if the entire stream network was considered. PMID- 26801155 TI - Growth and consumption of L-malic acid in wine-like medium by acclimated and non acclimated cultures of Patagonian Oenococcus oeni strains. AB - Five Oenococcus oeni strains, selected from spontaneous malolactic fermentation (MLF) of Patagonic Pinot noir wine, were assessed for their use as MLF starter cultures. After the individual evaluation of tolerance to some stress conditions, usually found in wine (pH, ethanol, SO2, and lysozyme), the behavior of the strains was analyzed in MLO broth with 14 % ethanol and pH 3.5 in order to test for the synergistic effect of high ethanol level and low pH and, finally, in a wine-like medium. Although the five strains were able to grow in MLO broth under low pH and/or high ethanol, they must be acclimated to grow in a wine-like medium. Additionally, glycosidase and tannase activities were evaluated, showing differences among the strains. The potential of the strains to ferment citrate was tested and two of the five strains showed the ability to metabolize this substrate. We did not detect the presence of genes encoding histidine, tyrosine descarboxylase, and putrescine carbamoyltransferase. All the strains tested exhibited good growth capacity and ability to consume L-malic acid in a wine-like medium after cell acclimation, and each of them showed a particular enzyme profile, which might confer different organoleptic properties to the wine. PMID- 26801156 TI - Stanozolol Decreases Bone Turnover Markers, Increases Mineralization, and Alters Femoral Geometry in Male Rats. AB - Stanozonol (ST) is a synthetic derivative of testosterone; it has anabolic/androgenic activity, increasing both the turnover of trabecular bone and the endocortical apposition of bone. The present study aimed to examine the effects of ST on bone status in rats by bone mineral content, markers of formation and resorption, bone density, and structural and microarchitectural parameters. Twenty male Wistar rats were randomly distributed into two experimental groups corresponding to placebo or ST administration, which consisted of weekly intramuscular injections of 10 mg/kg body weight of ST. Plasma parameters were analyzed by immunoassay. Bone mineral content was determined by spectrophotometry. Bone mineral density (BMD) and structural parameters were measured by peripheral quantitative computed tomography, and trabecular and cortical microarchitecture by micro-computed tomography. Plasma Ca, Mg, and alkaline phosphatase were higher, and urinary Ca excretion, corticosterone, and testosterone concentrations lower in the ST group. Femur Ca content was higher and P content was lower in the ST, whereas osteocalcin, aminoterminal propeptides of type I procollagen, and C-terminal telopeptides of type I collagen were lower. Total cross-sectional, trabecular, and cortical/subcortical areas were lower in the ST. No differences were observed on BMD and area parameters of the diaphysis as well as on trabecular and cortical microarchitecture. The use of ST increases bone mineralization, ash percentage, and Ca and Mg content in femur. In spite of an absence of changes in BMD, geometric metaphyseal changes were observed. We conclude that ST alters bone geometry, leads to low bone turnover, and thus may impair bone quality. PMID- 26801157 TI - Immunohistochemistry and real-time PCR as diagnostic tools for detection of Borrelia burgdorferi sensu lato in ticks collected from humans. AB - The objective of this study was to evaluate different methods used for detection of Borrelia burgdorferi sensu lato (s.l.) in ticks: immunohistochemistry followed by focus floating microscopy (FFM) and real-time polymerase chain reaction (real time PCR) targeting the ospA and hbb genes. Additionally, an optimized ospA real time PCR assay was developed with an integrated internal amplification control (IAC) for the detection of inhibition in the PCR assay and was validated as an improved screening tool for B. burgdorferi. One hundred and thirty-six ticks collected from humans in a hospital from Cluj-Napoca, Romania, were investigated regarding genus, stage of development and sex, and then tested by all three assays. A poor quality of agreement was found between FFM and each of the two real-time PCR assays, as assessed by concordance analysis (Cohen's kappa), whereas the agreement between the two real-time PCR assays was moderate. The present study argues for a low sensitivity of FFM and underlines that discordant results of different assays used for detection of B. burgdorferi in ticks are frequent. PMID- 26801158 TI - Factors influencing the prevalence and infestation levels of Varroa destructor in honeybee colonies in two highland agro-ecological zones of Uganda. AB - Varroa mites are ecto-parasites of honeybees and are a threat to the beekeeping industry. We identified the haplotype of Varroa mites and evaluated potential factors that influence their prevalence and infestation levels in the eastern and western highland agro-ecological zones of Uganda. This was done by collecting samples of adult worker bees between December 2014 and September 2015 in two sampling moments. Samples of bees were screened for Varroa using the ethanol wash method and the mites were identified by molecular techniques. All DNA sequences obtained from sampled mite populations in the two zones were 100 % identical to the Korean Haplotype (AF106899). Mean mite prevalence in the apiaries was 40 and 53 % for the western and eastern zones, respectively, during the first sampling. Over the second sampling, mean mite prevalence increased considerably in the western (59 %) but not in the eastern (51 %) zone. Factors that were associated with Varroa mite infestation levels include altitude, nature of apiary slope and apiary management practices during the first sampling. Our results further showed that Varroa mites were spreading from lower to higher elevations. Feral colonies were also infested with Varroa mites at infestation levels not significantly different from those in managed colonies. Colony productivity and strength were not correlated to mite infestation levels. We recommend a long-term Varroa mite monitoring strategy in areas of varying landscape and land use factors for a clear understanding of possible changes in mite infestation levels among African honeybees for informed decision making. PMID- 26801159 TI - Targeting Transcriptional and Epigenetic Reprogramming in Stromal Cells in Fibrosis and Cancer. AB - The basis of many human diseases arises from both genetic and epigenetic regulation. Recent advances in the understanding of the mechanisms underlying transcriptional and epigenetic regulation and their prevalence as contributors to a diverse range of human diseases have led us to focus on transcription and epigenetic changes in a variety of human disease conditions. Specifically, our recent studies in liver fibrosis and pancreatic cancer have demonstrated that the epigenetic regulation in hepatic stellate cells (HSCs) and pancreatic stellate cells (PSCs) significantly contributes to the progress in such diseases and presents great therapeutic potential. We show that the vitamin D receptor (VDR) acts as a master genomic suppressor in both HSC and PSC activation. The studies also have demonstrated that the VDR ligand reduces fibrosis and inflammation in a murine liver fibrosis and pancreatitis model. Although our current studies focus on characterizing the roles of VDR and regulatory regions within gene promoters and regulatory enhancers, we have expanded our effort to epigenetic mechanisms as major determinants of gene activation and repression in order to develop potential therapeutics to modulate stroma-associated pathologies including inflammation, fibrosis, and cancer. PMID- 26801160 TI - Genome Organization and Chromosome Architecture. AB - How the same DNA sequences can function in the three-dimensional architecture of interphase nucleus, fold in the very compact structure of metaphase chromosomes, and go precisely back to the original interphase architecture in the following cell cycle remains an unresolved question to this day. The solution to this question presented here rests on the correlations that were found to hold between the isochore organization of the genome and the architecture of chromosomes from interphase to metaphase. The key points are the following: (1) The transition from the looped domains and subdomains of interphase chromatin to the 30-nm fiber loops of early prophase chromosomes goes through their unfolding into an extended chromatin structure (probably a 10-nm "beads-on-a-string" structure); (2) the architectural proteins of interphase chromatin, such as CTCF and cohesin subunits, are retained in mitosis and are part of the discontinuous protein scaffold of mitotic chromosomes; and (3) the conservation of the link between architectural proteins and their binding sites on DNA through the cell cycle explains the reversibility of the interphase to mitosis process and the "mitotic memory" of interphase architecture. PMID- 26801161 TI - Inter-observer and inter-examination variability of manual vertebral bone attenuation measurements on computed tomography. AB - OBJECTIVE: To determine inter-observer and inter-examination variability of manual attenuation measurements of the vertebrae in low-dose unenhanced chest computed tomography (CT). METHODS: Three hundred and sixty-seven lung cancer screening trial participants who underwent baseline and repeat unenhanced low dose CT after 3 months because of an indeterminate lung nodule were included. The CT attenuation value of the first lumbar vertebrae (L1) was measured in all CTs by one observer to obtain inter-examination reliability. Six observers performed measurements in 100 randomly selected CTs to determine agreement with limits of agreement and Bland-Altman plots and reliability with intraclass correlation coefficients (ICCs). Reclassification analyses were performed using a threshold of 110 HU to define osteoporosis. RESULTS: Inter-examination reliability was excellent with an ICC of 0.92 (p < 0.001). Inter-examination limits of agreement ranged from -26 to 28 HU with a mean difference of 1 +/- 14 HU. Inter-observer reliability ICCs ranged from 0.70 to 0.91. Inter-examination variability led to 11.2 % reclassification of participants and inter-observer variability led to 22.1 % reclassification. CONCLUSIONS: Vertebral attenuation values can be manually quantified with good to excellent inter-examination and inter-observer reliability on unenhanced low-dose chest CT. This information is valuable for early detection of osteoporosis on low-dose chest CT. KEY POINTS: * Vertebral attenuation values can be manually quantified on low-dose unenhanced CT reliably. * Vertebral attenuation measurements may be helpful in detecting subclinical low bone density. * This could become of importance in the detection of osteoporosis. PMID- 26801162 TI - Imaging the renal lesion with dual-energy multidetector CT and multi-energy applications in clinical practice: what can it truly do for you? AB - OBJECTIVE: Many fortuitously detected renal lesions are incompletely characterised at traditional MDCT imaging, thus posing daily challenges to radiologists and referring physicians. There is burgeoning evidence that dual energy MDCT and multi-energy applications provide an added value over traditional MDCT imaging in renal lesion characterisation and throughput. This special report gives a vendor-neutral outlook on technical essentials, recommended protocols, high-yield clinical opportunities and reviews radiation dose aspects of dual energy MDCT imaging and multi-energy applications in renal lesions. In addition to a guide on interpretative traps and emerging problems, we provide an update on new, potential imaging horizons. CONCLUSION: Dual-energy MDCT and multi-energy applications can facilitate the imaging interpretation and throughput of renal lesions. Conjointly with capitalisation on the benefits, familiarity with dual- and multi-energy data sets as well as continuous scrutiny of interpretative traps can be the keys to the successful implementation and enhanced clinical acceptance of this powerful technique in the imaging community. Continuous advances in hardware and computer interfaces are expected to pave the way for the further expansion of the application spectrum. KEY POINTS: * Optimal protocols must be adopted for leveraging dual-energy benefits in renal imaging. * Virtual monochromatic imaging can overcome renal cyst pseudoenhancement. * Iodine maps help to interpret renal lesions incompletely characterised at traditional MDCT. * Interpretative traps need to be weighed-up in dual-energy renal lesions imaging. * Technical advances are expanding the dual-energy applications spectrum for renal lesions imaging. PMID- 26801163 TI - Effect of perioperative parecoxib sodium on postoperative pain control for transcatheter arterial chemoembolization for inoperable hepatocellular carcinoma: a prospective randomized trial. AB - OBJECTIVES: Pain is one of the most common side effects of transcatheter arterial chemoembolization (TACE) treatment. This study aimed to assess the analgesic effect of parecoxib sodium for postoperative pain control in patients with inoperable hepatocellular carcinoma (HCC) undergoing TACE. MATERIALS AND METHODS: This randomized placebo-controlled prospective clinical study was conducted at a single cancer centre. Patients were randomly assigned to receive parecoxib sodium (experimental group; n = 60) or 0.9 % sodium chloride (control group; n = 60) 1 h before TACE and once every 12 h for 2 days after TACE. Pain level, morphine consumption, adverse events, and quality of life were evaluated and compared between the two groups. RESULTS: Pain scores, percentage distribution of pain categories, and morphine consumption were significantly lower in the experimental group than in the control group (P < 0.05). Fever score comparisons revealed significantly better body temperature balance in the experimental group than in the control group (P = 0.024). Quality-of-life scores in the experimental group were significantly better than those in the control group (P < 0.05). CONCLUSIONS: Our results demonstrate that the perioperative administration of parecoxib significantly improved its effectiveness in the control of postoperative pain after TACE. KEY POINTS: * Perioperative administration of parecoxib is effective for control of pain after TACE. * COX-2 inhibitors provide effective and safe pain control. * Parecoxib helps improve quality-of-life after TACE for patients with inoperable hepatocellular carcinoma. PMID- 26801164 TI - Tracheal CT morphology: correlation with distribution and extent of thoracic adipose tissue. AB - OBJECTIVE: To evaluate the relationship between adipose tissue measurements and anterior bowing of the posterior tracheal wall in a large nonselected group of patients undergoing CT pulmonary angiography (CTPA). METHODS: Consecutive patients undergoing CTPA over a 4-month period were analyzed retrospectively. Using an adapted scoring system (posterior bowing, flattening, mild/moderate or severe anterior bowing of the posterior tracheal membrane), the axial morphology and cross-sectional area of the trachea at the narrowest point and 1 cm above the aortic arch were evaluated. Measurements of adipose tissue were taken (anterior mediastinal fat width, sagittal upper abdominal diameter and subcutaneous fat thickness at the level of the costophrenic angle). Relationships between tracheal morphology and measurements of adipose tissue were analyzed. RESULTS: 296 patients were included (120 males, 176 females, mean age 59 years, range 19-90). Severe anterior bowing of the posterior tracheal wall correlated with increasing sagittal upper abdominal diameter (p = 0.002). Mild/moderate and severe anterior bowing of the posterior tracheal wall correlated with increasing mediastinal fat width (p = 0.000 and p = 0.031, respectively). Tracheal cross-sectional area was inversely correlated with increasing subcutaneous fat thickness (p = 0.022). CONCLUSION: The findings demonstrate a statistically significant relationship between CT tracheal morphology and adipose tissue measurements in a large nonselected population. KEY POINTS: * There is increasing interest in the effects of obesity on the airways. * A relationship between anterior bowing of the posterior tracheal wall and adipose tissue measurements is demonstrated. * This is of clinical relevance in an increasingly obese population. * Further studies with functional correlation are required. PMID- 26801166 TI - Why does removing inter-word spaces produce reading deficits? The role of parafoveal processing. AB - To examine the role of inter-word spaces during reading, we used a gaze contingent boundary paradigm to manipulate parafoveal preview (i.e., valid vs. invalid preview) in a normal text condition that contained spaces (e.g., "John decided to sell the table") and in an unsegmented text condition that contained random numbers instead of spaces (e.g.,"John4decided8to5sell9the7table"). Preview effects on mean first-fixation durations were larger for normal than unsegmented text conditions, and survival analyses revealed a delay in the onset of both preview validity and word-frequency effects on first-fixation durations for unsegmented relative to normal text. Taken together with simulations that were conducted using the E-Z Reader model, the present findings indicated that unsegmented text deficits reflect disruptions to both parafoveal processing and lexical processing. We discuss the implications of our results for models of eye movement control. PMID- 26801165 TI - Diffusion-weighted MR imaging of uterine leiomyomas following uterine artery embolization. AB - PURPOSE: To test whether variations in apparent diffusion coefficient (ADC) values of uterine leiomyomas after uterine artery embolization (UAE) may correlate with outcome and assess the effects of UAE on leiomyomas and normal myometrium with magnetic resonance imaging (MRI). METHODS: Data of 49 women who underwent pelvic MRI before and after UAE were retrospectively reviewed. Uterine and leiomyoma volumes, ADC values of leiomyomas, and normal myometrium were calculated before and after UAE. RESULTS: By comparison with baseline ADC values, a significant drop in leiomyoma ADC was found at 6-month post-UAE (1.096 * 10(-3) mm(2)/s vs. 0.712 * 10(-3) mm(2)/s, respectively; p < 0.0001), but not at 48-h post-UAE. Leiomyoma devascularization was complete in 40/49 women (82 %) at 48 h and in 37/49 women (76 %) at 6 months. Volume reduction and leiomyoma ADC values at 6 months correlated with the degree of devascularization. There was a significant drop in myometrium ADC after UAE. Perfusion defect of the myometrium was observed at 48 h in 14/49 women (28.5 %) in association with higher degrees of leiomyoma devascularization. CONCLUSION: Six months after UAE, drop in leiomyoma ADC values and volume reduction correlate with the degree of leiomyoma devascularization. UAE affects the myometrium as evidenced by a drop in ADC values and initial myometrial perfusion defect. KEY POINTS: * A drop in leiomyoma ADC values is observed 6 months after UAE. * Drop in leiomyoma ADC value is associated with leiomyoma devascularizarion after UAE. * MR 48 h post-UAE allows assessing leiomyoma devascularization. * Myometrium perfusion defect occurs more often in women with a smaller uterus. PMID- 26801167 TI - Identification and gene-silencing of a putative odorant receptor transcription factor in Varroa destructor: possible role in olfaction. AB - The ectoparasitic mite Varroa destructor is one of the major threats to apiculture. Using a behavioural choice bioassay, we determined that phoretic mites were more successful in reaching a bee than reproductive mites, suggesting an energy trade-off between reproduction and host selection. We used both chemo ecological and molecular strategies to identify the regulation of the olfactory machinery of Varroa and its association with reproduction. We focused on transcription regulation. Using primers designed to the conserved DNA binding region of transcription factors, we identified a gene transcript in V. destructor homologous to the pheromone receptor transcription factor (PRTF) gene of Pediculus humanus corporis. Quantitative PCR (qPCR) revealed that this PRTF-like gene transcript is expressed in the forelegs at higher levels than in the body devoid of forelegs. Subsequent comparative qPCR analysis showed that transcript expression was significantly higher in the phoretic as compared to the reproductive stage. Electrophysiological and behavioural studies revealed a reduction in the sensitivity of PRTF RNA interference-silenced mites to bee headspace, consistent with a reduction in the mites' ability to reach a host. In addition, vitellogenin expression was stimulated in PRTF-silenced mites to similar levels as found in reproductive mites. These data shed light upon the regulatory mechanism of host chemosensing in V. destructor. PMID- 26801168 TI - Recent advances on separation and characterization of human milk oligosaccharides. AB - Free human milk oligosaccharides (HMOs) are unique due to their highly complex nature and important emerging biological and protective functions during early life such as prebiotic activity, pathogen deflection, and epithelial and immune cell modulation. Moreover, four genetically determined heterogeneous HMO secretory groups are known to be based on their structure and composition. Over the years, several analytical techniques have been applied to characterize and quantitate HMOs, including nuclear magnetic resonance spectroscopy, high performance liquid chromatography (HPLC), high pH anion-exchange chromatography, off-line and on-line mass spectrometry (MS), and capillary electrophoresis (CE). Even if these techniques have proven to be efficient and simple, most glycans have no significant UV absorption and derivatization with fluorophore groups prior to separation usually results in higher sensitivity and an improved chromatographic/electrophoretic profile. Consequently, the analysis by HPLC/CE of derivatized milk oligosaccharides with different chromophoric active tags has been developed. However, UV or fluorescence detection does not provide specific structural information and this is a key point in particular related to the highly complex nature of the milk glycan mixtures. As a consequence, for a specific determination of complex mixtures of oligomers, analytical separation is usually required with evaluation by means of MS, which has been successfully applied to HMOs, resulting in efficient compositional analysis and profiling in various milk samples. This review aims to give an overview of the current state of-the-art techniques used in HMO analysis. PMID- 26801169 TI - beta-Caryophyllene Attenuates Focal Cerebral Ischemia-Reperfusion Injury by Nrf2/HO-1 Pathway in Rats. AB - This study aimed to identify the effect of beta-caryophyllene (BCP) pretreatment and elucidate the Nrf2/HO-1 signaling mechanism after focal cerebral ischemia reperfusion (I-R) injury in rats. Adult male Sprague-Dawley rats were randomly assigned to the sham-operated group, I-R group and BCP pretreated I-R group. At 24 h after reperfusion, neurological deficits and infarct volume were evaluated. Pathological changes of neuron in hippocampuses were observed by Nissil staining and transmission electron microscopy (TEM). Oxidative stress was assessed by malondialdehyde (MDA) level, lipid peroxidation (LPO), nitric oxide (NO), superoxide dismutase (SOD) and Catalase (CAT) activity. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were analysed by Western blotting and real-time quantitative polymerase chain reaction (Q-PCR). The protein expression of Bcl-2 and Bax was determined by immunohistochemistry. Apoptotic cells were detected using TUNEL staining. In I-R group, neurological deficit scores, cerebral infarct volume, MDA levels, LPO content, NO level, expression of Bax and TUNEL-positive cells were found to be increased at 24 h after I-R injury, while SOD activity, CAT activity and expression of Bcl-2 were decreased. However, results in the BCP pretreatment groups were reversed. And the protein and mRNA expressions of Nrf2 and HO-1 were significantly up-regulated in the BCP pretreated I-R group. Results of Nissil staining and TEM scan manifested that BCP remarkablely improved neuronal injury after I-R in rats. All the above suggested that BCP pretreatment played a neuroprotective role in cerebral I-R injury, which might be exerted by upregulating the expression of Nrf2 and HO-1 to ameliorate oxidative damage and neuronal apoptosis. PMID- 26801170 TI - The Emerging Therapeutic Role of NGF in Alzheimer's Disease. AB - Alzheimer's disease (AD) is the most common type of neurodegenerative dementia that affects the elderly population. Nerve growth factor (NGF) contributes to the survival, regeneration and death of neurons during aging and in neurodegenerative diseases. Recently, research has shown that NGF is related to the pathology, mechanisms and symptoms of AD. Therefore, there is a need to summarize the new advancements in NGF research and its potential therapeutic implications in AD. In this review, we will focus on NGF distribution, production, and function; the interaction of Abeta and NGF; and the effect of different therapy methods on AD. In summary, we hope to describe the experimental and clinical data demonstrating the important roles of NGF for AD treatment. PMID- 26801171 TI - ATP-Evoked Intracellular Ca2+ Signaling of Different Supporting Cells in the Hearing Mouse Hemicochlea. AB - Hearing and its protection is regulated by ATP-evoked Ca(2+) signaling in the supporting cells of the organ of Corti, however, the unique anatomy of the cochlea hampers observing these mechanisms. For the first time, we have performed functional ratiometric Ca(2+) imaging (fura-2) in three different supporting cell types in the hemicochlea preparation of hearing mice to measure purinergic receptor-mediated Ca(2+) signaling in pillar, Deiters' and Hensen's cells. Their resting [Ca(2+)]i was determined and compared in the same type of preparation. ATP evoked reversible, repeatable and dose-dependent Ca(2+) transients in all three cell types, showing desensitization. Inhibiting the Ca(2+) signaling of the ionotropic P2X (omission of extracellular Ca(2+)) and metabotropic P2Y purinergic receptors (depletion of intracellular Ca(2+) stores) revealed the involvement of both receptor types. Detection of P2X2,3,4,6,7 and P2Y1,2,6,12,14 receptor mRNAs by RT-PCR supported this finding and antagonism by PPADS suggested different functional purinergic receptor population in pillar versus Deiters' and Hensen's cells. The sum of the extra- and intracellular Ca(2+)-dependent components of the response was about equal with the control ATP response (linear additivity) in pillar cells, and showed supralinearity in Deiters' and Hensen's cells. Calcium induced calcium release might explain this synergistic interaction. The more pronounced Ca(2+) leak from the endoplasmic reticulum in Deiters' and Hensen's cells, unmasked by cyclopiazonic acid, may also suggests the higher activity of the internal stores in Ca(2+) signaling in these cells. Differences in Ca(2+) homeostasis and ATP-induced Ca(2+) signaling might reflect the distinct roles these cells play in cochlear function and pathophysiology. PMID- 26801172 TI - Metabolomics of Neurotransmitters and Related Metabolites in Post-Mortem Tissue from the Dorsal and Ventral Striatum of Alcoholic Human Brain. AB - We report on changes in neurotransmitter metabolome and protein expression in the striatum of humans exposed to heavy long-term consumption of alcohol. Extracts from post mortem striatal tissue (dorsal striatum; DS comprising caudate nucleus; CN and putamen; P and ventral striatum; VS constituted by nucleus accumbens; NAc) were analysed by high performance liquid chromatography coupled with tandem mass spectrometry. Proteomics was studied in CN by two-dimensional gel electrophoresis followed by mass-spectrometry. Proteomics identified 25 unique molecules expressed differently by the alcohol-affected tissue. Two were dopamine-related proteins and one a GABA-synthesizing enzyme GAD65. Two proteins that are related to apoptosis and/or neuronal loss (BiD and amyloid-beta A4 precursor protein binding family B member 3) were increased. There were no differences in the levels of dopamine (DA), 3,4-dihydrophenylacetic acid (DOPAC), serotonin (5HT), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (HIAA), histamine, L glutamate (Glu), gamma-aminobutyric acid (GABA), tyrosine (Tyr) and tryptophan (Tryp) between the DS (CN and P) and VS (NAc) in control brains. Choline (Ch) and acetylcholine (Ach) were higher and norepinephrine (NE) lower, in the VS. Alcoholic striata had lower levels of neurotransmitters except for Glu (30 % higher in the alcoholic ventral striatum). Ratios of DOPAC/DA and HIAA/5HT were higher in alcoholic striatum indicating an increase in the DA and 5HT turnover. Glutathione was significantly reduced in all three regions of alcohol-affected striatum. We conclude that neurotransmitter systems in both the DS (CN and P) and the VS (NAc) were significantly influenced by long-term heavy alcohol intake associated with alcoholism. PMID- 26801173 TI - Dietary Calorie Restriction from Adulthood Through Old Age in Rats: Improved DNA Polymerase beta and DNA Gap Repair Activity in Cortical Neurons. AB - It is well established now that dietary calorie restriction (CR) leads to extension of life span in many species, although the exact mechanism of this effect is still eluding. In the present study, we examined the effect of 40 % CR imposed during a prolonged period of life span (from 6 to 30 months) of rats on the activity of DNA polymerase beta (pol beta) in view of its role in short gap base excision DNA repair and template driven primer extension. DNA pol beta activity is very low at this late age. However, cortical neuronal extracts prepared from CR rats of 30 months age showed significantly higher pol beta protein levels and activity when compared to control 30 month old rats. Yet, one nucleotide gap repair in old control neurons and an improved efficiency in CR neurons could be visualized only after supplementation of the extracts with T4 DNA ligase indicating the lack of CR affect on ligase activity. No impressive primer extension activity is seen either in the CR or old control neurons. These results are taken to convey that extended CR through adult life leads to improved pol beta activity and therefore, pol beta dependent DNA gap repair activity. PMID- 26801174 TI - CXCL12/CXCR4 Axis Improves Migration of Neuroblasts Along Corpus Callosum by Stimulating MMP-2 Secretion After Traumatic Brain Injury in Rats. AB - To investigate the effect of CXCL12 on migration of neural precursor cells after traumatic brain injury (TBI). We randomly divided 48 rats into four groups: (1) the sham group, rats were performed craniotomy only, (2) the control group, saline were injected into the ipsilateral cortex after TBI, (3) the CXCL12 group, CXCL12 were injected into the ipsilateral cortex after TBI, and (4) the CXCL12 + AMD3100 group, CXCL12 and AMD3100 were mixed together and injected into the ipsilateral cortex after TBI. At 7 days after TBI, the brain tissues were subjected to immunofluorescent double-labeled staining with the antibodies of CXCR4/DCX, MMP-2/DCX, MMP-2/GFAP, MMP-2/NeuN. Western blot assay was used to measure the protein levels of MMP-2. Compared with the control group, the number of CXCR4/DCX and MMP-2 positive cells around the injured corpus callosum area were significantly increased in the CXCL12 treatment group. The area occupied by these cells expanded and the shape changed from chain distribution to radial. CXCL12 + AMD3100 treatment significantly decreased the number and distribution area of CXCR4/DCX and MMP-2 positive cells compared with the CXCL12 treatment and control group. The DCX positive cells could not form chain or radial distribution. The protein expressions of MMP-2 had the similar change trends as the results of immunofluorescent staining. MMP-2 could be secreted by DCX, GFAP and NeuN positive cells. CXCL12/CXCR4 axis can improve the migration of the neuroblasts along the corpus callosum by stimulating the MMP-2 secretion of different types of cells. PMID- 26801175 TI - Carnosine Reduces Oxidative Stress and Reverses Attenuation of Righting and Postural Reflexes in Rats with Thioacetamide-Induced Liver Failure. AB - Cerebral oxidative stress (OS) contributes to the pathogenesis of hepatic encephalopathy (HE). Existing evidence suggests that systemic administration of L histidine (His) attenuates OS in brain of HE animal models, but the underlying mechanism is complex and not sufficiently understood. Here we tested the hypothesis that dipeptide carnosine (beta-alanyl-L-histidine, Car) may be neuroprotective in thioacetamide (TAA)-induced liver failure in rats and that, being His metabolite, may mediate the well documented anti-OS activity of His. Amino acids [His or Car (100 mg/kg)] were administrated 2 h before TAA (i.p., 300 mg/kg 3* in 24 h intervals) injection into Sprague-Dawley rats. The animals were thus tested for: (i) brain prefrontal cortex and blood contents of Car and His, (ii) amount of reactive oxygen species (ROS), total antioxidant capacity (TAC), GSSG/GSH ratio and thioredoxin reductase (TRx) activity, and (iii) behavioral changes (several models were used, i.e. tests for reflexes, open field, grip test, Rotarod). Brain level of Car was reduced in TAA rats, and His administration significantly elevated Car levels in control and TAA rats. Car partly attenuated TAA-induced ROS production and reduced GSH/GSSG ratio, whereas the increase of TRx activity in TAA brain was not significantly modulated by Car. Further, Car improved TAA-affected behavioral functions in rats, as was shown by the tests of righting and postural reflexes. Collectively, the results support the hypothesis that (i) Car may be added to the list of neuroprotective compounds of therapeutic potential on HE and that (ii) Car mediates at least a portion of the OS-attenuating activity of His in the setting of TAA-induced liver failure. PMID- 26801176 TI - Mdivi-1 Protects Epileptic Hippocampal Neurons from Apoptosis via Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress in Vitro. AB - Mitochondrial division inhibitor 1 (mdivi-1), a selective inhibitor of the mitochondrial fission protein dynamin-related protein 1, has been proposed to have a neuroprotective effect on hippocampal neurons in animal models of epilepsy. However, the effect of mdivi-1 on epileptic neuronal death in vitro remains unknown. Therefore, we investigated the effect of mdivi-1 and the underlying mechanisms in the hippocampal neuronal culture (HNC) model of acquired epilepsy (AE) in vitro. We found that mitochondrial fission was increased in the HNC model of AE and inhibition of mitochondrial fission by mdivi-1 significantly decreased neuronal apoptosis induced by AE. In addition, mdivi-1 pretreatment significantly attenuated oxidative stress induced by AE characterized by decrease of reactive oxygen species (ROS) production and malondialdehyde level and by increase of superoxide dismutase activity. Moreover, mdivi-1 pretreatment significantly decreased endoplasmic reticulum (ER) stress markers glucose regulated protein 78, C/EBP homologous protein expression and caspase-3 activation. Altogether, our findings suggest that mdivi-1 protected against AE induced hippocampal neuronal apoptosis in vitro via decreasing ROS-mediated oxidative stress and ER stress. PMID- 26801177 TI - Degradation and transformation of 17alpha-estradiol in water-sediment systems under controlled aerobic and anaerobic conditions. AB - One of the principal metabolites in cattle excreta following the administration of Synovex(r) ONE, which contains estradiol benzoate and trenbolone acetate, is 17alpha-estradiol. As part of the environmental assessment of the use of Synovex ONE, data were generated to characterize the fate of 17alpha-estradiol in the environment. Studies were conducted to determine the degradation and transformation of 17alpha-[14 C]-estradiol in 2 representative water-sediment systems each under aerobic and anaerobic conditions. The same transformation products-estriol, 17beta-estradiol, and estrone-were formed, principally in the sediment phase, under both conditions in both systems. From the production of these transformation products, the 50% disappearance time (DT50) values of estrone and 17beta-estradiol were determined, along with the DT50 values of 17alpha-estradiol and the total drug (17alpha-estradiol + 17beta-estradiol + estrone). The results indicate that 17 alpha-[14 C]-estradiol was more persistent under anaerobic conditions than under aerobic conditions and that 17 alpha-[14 C] estradiol was less persistent than its transformation products. The DT50 values for the total system (aqueous and sediment phases) and for the total residues (17alpha-estradiol, 17beta-estradiol, and estrone) were selected for use in modeling the environmental fate of estradiol benzoate. For aerobic degradation in the water-sediment system, the DT50 was 31.1 d, and it was 107.8 d for the anaerobic system. Environ Toxicol Chem 2017;36:621-629. (c) 2016 SETAC. PMID- 26801178 TI - Hedgehog Signaling Strength Is Orchestrated by the mir-310 Cluster of MicroRNAs in Response to Diet. AB - Since the discovery of microRNAs (miRNAs) only two decades ago, they have emerged as an essential component of the gene regulatory machinery. miRNAs have seemingly paradoxical features: a single miRNA is able to simultaneously target hundreds of genes, while its presence is mostly dispensable for animal viability under normal conditions. It is known that miRNAs act as stress response factors; however, it remains challenging to determine their relevant targets and the conditions under which they function. To address this challenge, we propose a new workflow for miRNA function analysis, by which we found that the evolutionarily young miRNA family, the mir-310s (mir-310/mir-311/mir-312/mir-313), are important regulators of Drosophila metabolic status. mir-310s-deficient animals have an abnormal diet dependent expression profile for numerous diet-sensitive components, accumulate fats, and show various physiological defects. We found that the mir-310s simultaneously repress the production of several regulatory factors (Rab23, DHR96, and Ttk) of the evolutionarily conserved Hedgehog (Hh) pathway to sharpen dietary response. As the mir-310s expression is highly dynamic and nutrition sensitive, this signal relay model helps to explain the molecular mechanism governing quick and robust Hh signaling responses to nutritional changes. Additionally, we discovered a new component of the Hh signaling pathway in Drosophila, Rab23, which cell autonomously regulates Hh ligand trafficking in the germline stem cell niche. How organisms adjust to dietary fluctuations to sustain healthy homeostasis is an intriguing research topic. These data are the first to report that miRNAs can act as executives that transduce nutritional signals to an essential signaling pathway. This suggests miRNAs as plausible therapeutic agents that can be used in combination with low calorie and cholesterol diets to manage quick and precise tissue-specific responses to nutritional changes. PMID- 26801179 TI - Genomic Patterns of Geographic Differentiation in Drosophila simulans. AB - Geographic patterns of genetic differentiation have long been used to understand population history and to learn about the biological mechanisms of adaptation. Here we present an examination of genomic patterns of differentiation between northern and southern populations of Australian and North American Drosophila simulans, with an emphasis on characterizing signals of parallel differentiation. We report on the genomic scale of differentiation and functional enrichment of outlier SNPs. While, overall, signals of shared differentiation are modest, we find the strongest support for parallel differentiation in genomic regions that are associated with regulation. Comparisons to Drosophila melanogaster yield potential candidate genes involved in local adaptation in both species, providing insight into common selective pressures and responses. In contrast to D. melanogaster, in D. simulans we observe patterns of variation that are inconsistent with a model of temperate adaptation out of a tropical ancestral range, highlighting potential differences in demographic and colonization histories of this cosmopolitan species pair. PMID- 26801181 TI - Context-Dependent Sensitivity to Mutations Disrupting the Structural Integrity of Individual EGF Repeats in the Mouse Notch Ligand DLL1. AB - The highly conserved Notch-signaling pathway mediates cell-to-cell communication and is pivotal for multiple developmental processes and tissue homeostasis in adult organisms. Notch receptors and their ligands are transmembrane proteins with multiple epidermal-growth-factor-like (EGF) repeats in their extracellular domains. In vitro the EGF repeats of mammalian ligands that are essential for Notch activation have been defined. However, in vivo the significance of the structural integrity of each EGF repeat in the ligand ectodomain for ligand function is still unclear. Here, we analyzed the mouse Notch ligand DLL1. We expressed DLL1 proteins with mutations disrupting disulfide bridges in each individual EGF repeat from single-copy transgenes in the HPRT locus of embryonic stem cells. In Notch transactivation assays all mutations impinged on DLL1 function and affected both NOTCH1 and NOTCH2 receptors similarly. An allelic series in mice that carried the same point mutations in endogenous Dll1, generated using a mini-gene strategy, showed that early developmental processes depending on DLL1-mediated NOTCH activation were differently sensitive to mutation of individual EGF repeats in DLL1. Notably, some mutations affected only somite patterning and resulted in vertebral column defects resembling spondylocostal dysostosis. In conclusion, the structural integrity of each individual EGF repeat in the extracellular domain of DLL1 is necessary for full DLL1 activity, and certain mutations in Dll1 might contribute to spondylocostal dysostosis in humans. PMID- 26801180 TI - Unique and Overlapping Functions of Formins Frl and DAAM During Ommatidial Rotation and Neuronal Development in Drosophila. AB - The noncanonical Frizzled/planar cell polarity (PCP) pathway regulates establishment of polarity within the plane of an epithelium to generate diversity of cell fates, asymmetric, but highly aligned structures, or to orchestrate the directional migration of cells during convergent extension during vertebrate gastrulation. In Drosophila, PCP signaling is essential to orient actin wing hairs and to align ommatidia in the eye, in part by coordinating the movement of groups of photoreceptor cells during ommatidial rotation. Importantly, the coordination of PCP signaling with changes in the cytoskeleton is essential for proper epithelial polarity. Formins polymerize linear actin filaments and are key regulators of the actin cytoskeleton. Here, we show that the diaphanous-related formin, Frl, the single fly member of the FMNL (formin related in leukocytes/formin-like) formin subfamily affects ommatidial rotation in the Drosophila eye and is controlled by the Rho family GTPase Cdc42. Interestingly, we also found that frl mutants exhibit an axon growth phenotype in the mushroom body, a center for olfactory learning in the Drosophila brain, which is also affected in a subset of PCP genes. Significantly, Frl cooperates with Cdc42 and another formin, DAAM, during mushroom body formation. This study thus suggests that different formins can cooperate or act independently in distinct tissues, likely integrating various signaling inputs with the regulation of the cytoskeleton. It furthermore highlights the importance and complexity of formin dependent cytoskeletal regulation in multiple organs and developmental contexts. PMID- 26801182 TI - Static and Dynamic Factors Limit Chromosomal Replication Complexity in Escherichia coli, Avoiding Dangers of Runaway Overreplication. AB - We define chromosomal replication complexity (CRC) as the ratio of the copy number of the most replicated regions to that of unreplicated regions on the same chromosome. Although a typical CRC of eukaryotic or bacterial chromosomes is 2, rapidly growing Escherichia coli cells induce an extra round of replication in their chromosomes (CRC = 4). There are also E. coli mutants with stable CRC~6. We have investigated the limits and consequences of elevated CRC in E. coli and found three limits: the "natural" CRC limit of ~8 (cells divide more slowly); the "functional" CRC limit of ~22 (cells divide extremely slowly); and the "tolerance" CRC limit of ~64 (cells stop dividing). While the natural limit is likely maintained by the eclipse system spacing replication initiations, the functional limit might reflect the capacity of the chromosome segregation system, rather than dedicated mechanisms, and the tolerance limit may result from titration of limiting replication factors. Whereas recombinational repair is beneficial for cells at the natural and functional CRC limits, we show that it becomes detrimental at the tolerance CRC limit, suggesting recombinational misrepair during the runaway overreplication and giving a rationale for avoidance of the latter. PMID- 26801183 TI - A Conserved GEF for Rho-Family GTPases Acts in an EGF Signaling Pathway to Promote Sleep-like Quiescence in Caenorhabditis elegans. AB - Sleep is evolutionarily conserved and required for organism homeostasis and survival. Despite this importance, the molecular and cellular mechanisms underlying sleep are not well understood. Caenorhabditis elegans exhibits sleep like behavioral quiescence and thus provides a valuable, simple model system for the study of cellular and molecular regulators of this process. In C. elegans, epidermal growth factor receptor (EGFR) signaling is required in the neurosecretory neuron ALA to promote sleep-like behavioral quiescence after cellular stress. We describe a novel role for VAV-1, a conserved guanine nucleotide exchange factor (GEF) for Rho-family GTPases, in regulation of sleep like behavioral quiescence. VAV-1, in a GEF-dependent manner, acts in ALA to suppress locomotion and feeding during sleep-like behavioral quiescence in response to cellular stress. Additionally, VAV-1 activity is required for EGF induced sleep-like quiescence and normal levels of EGFR and secretory dense core vesicles in ALA. Importantly, the role of VAV-1 in promoting cellular stress induced behavioral quiescence is vital for organism health because VAV-1 is required for normal survival after cellular stress. PMID- 26801184 TI - Structural brain correlates of heart rate variability in a healthy young adult population. AB - The high frequency component of heart rate variability (HRV) has reliably been shown to serve as an index of autonomic inhibitory control and is increasingly considered as a biomarker of adaptability and health. While several functional neuroimaging studies identified associations between regional cerebral blood flow and HRV, studies on structural brain correlates of HRV are scarce. We investigated whether interindividual differences in HRV are related to brain morphology in healthy humans. Thirty participants underwent HRV recording at rest subsequent to structural magnetic resonance imaging. Cortical reconstruction and subcortical volumetry were performed with the Freesurfer image analysis suite. The amount of resting HRV was positively correlated with the cortical thickness of an area within the right anterior midcingulate cortex (aMCC). Consistent with existing studies implicating forebrain regions in cardiac regulation, our findings show that the thickness of the right aMCC is associated with the degree of parasympathetic regulation of heart rate. Evidence for the neural correlates of interindividual differences in HRV may complement our understanding of the mechanisms underlying the association between HRV and self-regulatory capacity. PMID- 26801185 TI - Transabdominal midline reconstruction by minimally invasive surgery: technique and results. AB - BACKGROUND: The introduction of the minimally invasive approach changed the way abdominal surgery was carried out. Open suture and mesh reinforcement in ventral hernia repair used to be the surgeon's choice of procedure. Although the laparoscopic approach, with defect bridging and mesh fixation, has been described since 1993, the procedure remains largely unchanged. Evidence shows that defect closure and retro-muscular mesh positioning have the best outcomes and are the best surgical practice. We therefore aimed to develop and demonstrate a procedure which combined the good results of open surgery using the Rives-Stoppa principles, particularly in terms of recurrence, with all the benefits of minimally invasive surgery. METHODS: Between October 2012 and February 2014, 15 post-bariatric surgery patients underwent laparoscopic midline incisional hernia repair. The peritoneal cavity was accessed through a 5-mm optical view cannula at the superior left quadrant. A suprapubic and two right and left lower quadrant cannulas were inserted for inferior access and dissection. The defect adhesions were released. The whole midline was closed with an endoscopic linear stapler, including the defect, from the lower abdomen, 4 cm below the umbilicus, until the epigastric region, including posterior sheath mechanical suturing and cutting in the same movement. A retrorectus space was created in which a retro-muscular mesh was deployed. Fixation was done using a hernia stapler against the posterior sheath from the peritoneal cavity to the abdominal wall muscles. Selection was based on xifo-umbilical incisional midline hernias post open bariatric surgery. Pregnant women, cancer patients, or patients with clinical contraindications were excluded. RESULTS: The patients mean age was 51.2 years (range 39-67). Four patients were men and eleven women. Two had well-compensated fibromyalgia, four had diabetes, and five had hypertension. The mean BMI was 29.5 kg/m2 (range 23 31.6). Surgery was performed successfully in all cases through four ports; the number of incisional hernias was 3 +/- 2, with a mean maximum width of 3.75 cm (range 2.1-9) and maximum length of 14 cm (7.5-20.5). The mean surgical time was 114.3 min (range 85-170), and the median hospital stay was 1.4 days. No intra operative or immediate post-operative complication or death occurred. One patient had a seroma treated conservatively 1 week after surgery and another had a retro muscular infection treated with percutaneous drainage. CT-Scans made before and after the procedure, showed total closure of the defect. QOL questionnaire showed satisfaction, acceptance, and no complaints. CONCLUSION: Although the study involved a small number of patients, it has proved the technique to be feasible, easy to perform, and have the combined benefits of laparoscopic and open surgery. The results, shown by CT-scan, peri-operative, and QOL findings, were good. PMID- 26801186 TI - [Percutaneous access for endovascular therapy of PAOD. Femoral, popliteal and pedal]. AB - BACKGROUND: Percutaneous interventions in patients with peripheral arterial occlusive disease (PAOD) are usually performed from an antegrade or retrograde transfemoral arterial access; however, sometimes chronic femoropopliteal and crural occlusions cannot be negotiated via this route with traditional standard methods. OBJECTIVES: Description and evaluation of transfemoral, transpopliteal and transpedal vascular approaches for the treatment of advanced PAOD. MATERIAL AND METHODS: A literature review of available studies on endovascular interventions with distal retrograde access was carried out. RESULTS: Most complex arterial occlusions can be treated by employing modern subintimal procedures and/or additional retrograde approaches. The success rate also depends on the expertise with the appropriate technique and materials used. CONCLUSION: The transfemoral access remains the first choice for the treatment of patients with PAOD. Additional retrograde approaches from a more distal access constitute an alternative after failure of antegrade intervention attempts. PMID- 26801187 TI - [Selected clinically established and scientific techniques of diffusion-weighted MRI. In the context of imaging in oncology]. AB - BACKGROUND: Diffusion-weighted imaging (DWI) is a magnetic resonance imaging (MRI) technique that was established in the clinical routine primarily for the detection of brain ischemia. In the past 15 years its clinical use has been extended to oncological radiology, as tumor and metastases can be depicted in DWI due to their hypercellular nature. PRINCIPLES: The basis of DWI is the Stejskal Tanner experiment. The diffusion properties of tissue can be visualized after acquisition of at least two diffusion-weighted series using echo planar imaging and a specific sequence of gradient pulses. CLINICAL APPLICATIONS: The use of DWI in prostate MRI was reported to be one of the first established applications that found its way into internationally recognized clinical guidelines of the European Society of Urological Radiology (ESUR) and the prostate imaging reporting and data system (PI-RADS) scale. Due to recently reported high specificity and negative predictive values of 94% and 92%, respectively, its regular use for breast MRI is expected in the near future. Furthermore, DWI can also reliably be used for whole-body imaging in patients with multiple myeloma or for measuring the extent of bone metastases. OUTLOOK: New techniques in DWI, such as intravoxel incoherent motion imaging, diffusion kurtosis imaging and histogram-based analyses represent promising approaches to achieve a more quantitative evaluation for tumor detection and therapy response. PMID- 26801188 TI - Ceramide channels and mitochondrial outer membrane permeability. AB - Among the permeability pathways in the mitochondrial outer membrane (MOM), whose elucidation was pioneered by Kathleen Kinnally, there is one formed by the lipid, ceramide. Electron microscopic visualization shows that ceramide channels are large cylindrical structures of varying pore size, with a most frequent size of 10 nm in diameter, large enough to allow all soluble proteins to translocate between the cytosol and the mitochondrial intermembrane space. Similar results were obtained with electrophysiological measurements. Studies of the dynamics of the channels are consistent with a right cylinder. Ceramide channels form at mole fractions of ceramide that are found in the MOM early in the apoptotic process, before or at the time of protein release from mitochondria. That these channels are good candidates for the protein release pathway is supported by the fact that channel formation is inhibited by anti-apoptotic proteins and favored by Bax. Bcl xL inhibits ceramide channel formation by binding to the apolar ceramide tails using its hydrophobic grove. Bax interaction with the polar regions of ceramide results in MOM permeabilization through synergy with ceramide. Evidence that ceramide channels actually function to favor apoptosis in vivo is supported by the expression of Bcl-xL containing point mutations in cells induced to undergo apoptosis. The Bcl-xL mutants inhibit differentially Bax and ceramide channels and thus tease apart, to some extent, these two modes of MOM permeabilization. Ceramide channels have the right properties and appropriate regulation to be key players in the induction of apoptosis. PMID- 26801189 TI - Supine hypertension in Parkinson's disease and multiple system atrophy. AB - OBJECTIVE: Supine hypertension (SH) is a feature of cardiovascular autonomic failure that often accompanies orthostatic hypotension and may represent a negative prognostic factor in parkinsonian syndromes. Here we investigated the frequency rate as well as the clinical and tilt test correlates of SH in Parkinson's disease (PD) and multiple system atrophy (MSA). METHODS: 197 PD (33 demented) and 78 MSA (24 MSA-Cerebellar, 54 MSA-Parkinsonian) patients who had undergone a tilt test examination were retrospectively included. Clinical demographic characteristics were collected from clinical records at the time of the tilt test examination. RESULTS: SH (>140 mmHg systolic, >90 mmHg diastolic) occurred in 34 % of PD patients (n = 66, mild in 71 % of patients, moderate in 27 %, severe in 2 %) and 37 % of MSA ones (n = 29, mild in 55 % of patients, moderate in 17 %, severe in 28 %). No difference was observed in SH frequency between demented versus gender-, age- and disease duration-matched non-demented PD patients, or between patients with the parkinsonian (MSA-P) versus the cerebellar (MSA-C) variant of MSA. In PD, SH was associated with presence of cardiovascular comorbidities (p = 0.002) and greater systolic (p = 0.007) and diastolic (p = 0.002) orthostatic blood pressure fall. Orthostatic hypotension (p = 0.002), and to a lesser degree, lower daily dopaminergic intake (p = 0.01) and use of anti-hypertensive medications (p = 0.04) were associated with SH in MSA. INTERPRETATION: One-third of PD and MSA patients suffer from mild to severe SH, independently of age, disease duration or stage. In PD, cardiovascular comorbidities significantly contribute to the development of SH, while in MSA, SH appears to reflect cardiovascular autonomic failure. PMID- 26801190 TI - Pramipexole, a Dopamine D2/D3 Receptor-Preferring Agonist, Prevents Experimental Autoimmune Encephalomyelitis Development in Mice. AB - Experimental autoimmune encephalomyelitis (EAE) is the most used animal model of multiple sclerosis (MS) for the development of new therapies. Dopamine receptors can modulate EAE and MS development, thus highlighting the potential use of dopaminergic agonists in the treatment of MS, which has been poorly explored. Herein, we hypothesized that pramipexole (PPX), a dopamine D2/D3 receptor preferring agonist commonly used to treat Parkinson's disease (PD), would be a suitable therapeutic drug for EAE. Thus, we report the effects and the underlying mechanisms of action of PPX in the prevention of EAE. PPX (0.1 and 1 mg/kg) was administered intraperitoneally (i.p.) from day 0 to 40 post-immunization (p.i.). Our results showed that PPX 1 mg/kg prevented EAE development, abolishing EAE signs by blocking neuroinflammatory response, demyelination, and astroglial activation in spinal cord. Moreover, PPX inhibited the production of inflammatory cytokines, such as IL-17, IL-1beta, and TNF-alpha in peripheral lymphoid tissue. PPX was also able to restore basal levels of a number of EAE-induced effects in spinal cord and striatum, such as reactive oxygen species, glutathione peroxidase, parkin, and alpha-synuclein (alpha-syn). Thus, our findings highlight the usefulness of PPX in preventing EAE-induced motor symptoms, possibly by modulating immune cell responses, such as those found in MS and other T helper cell-mediated inflammatory diseases. PMID- 26801193 TI - Influence of previous surgery on patient-rated outcome after surgery for degenerative disorders of the lumbar spine. AB - PURPOSE: Few studies have used multivariate models to quantify the effect of multiple previous spine surgeries on patient-oriented outcome after spine surgery. This study sought to quantify the effect of prior spine surgery on 12 month postoperative outcomes in patients undergoing surgery for different degenerative disorders of the lumbar spine. METHODS: The study included 4940 patients with lumbar degenerative disease documented in the Spine Tango Registry of EUROSPINE, the Spine Society of Europe, from 2004 to 2015. Preoperatively and 12 months postoperatively, patients completed the multidimensional Core Outcome Measures Index (COMI; 0-10 scale). Patients' medical history and surgical details were recorded using the Spine Tango Surgery 2006 and 2011 forms. Multiple linear regression models were used to investigate the relationship between the number of previous surgeries and the 12-month postoperative COMI score, controlling for the baseline COMI score and other potential confounders. RESULTS: In the adjusted model including all cases, the 12-month COMI score showed a 0.37-point worse value [95 % confidence intervals (95 % CI) 0.29-0.45; p < 0.001] for each additional prior spine surgery. In the subgroup of patients with lumbar disc herniation, the corresponding effect was 0.52 points (95 % CI 0.27-0.77; p < 0.001) and in lumbar degenerative spondylolisthesis, 0.40 points (95 % CI 0.17 0.64; p = 0.001). CONCLUSIONS: We were able to demonstrate a clear "dose response" effect for previous surgery: the greater the number of prior spine surgeries, the systematically worse the outcome at 12 months' follow-up. The results of this study can be used when considering or consenting a patient for further surgery, to better inform the patient of the likely outcome and to set realistic expectations. PMID- 26801194 TI - Giant central thoracic disc herniations: surgical outcome in 17 consecutive patients treated by mini-thoracotomy. AB - PURPOSE: Safe treatment of giant central thoracic disc herniations (cTDHs) remains a surgical challenge due to frequent calcifications, intradural extension and, importantly, the rare exposure of spine surgeons to these lesions. We report our 10-year experience in the management of giant cTDH by mini-thoracotomy and offer a detailed description of the technique. METHODS: 17 patients harboring 17 giant cTDH operated on via a mini-thoracotomy at the authors' institution between 2004 and 2014 were reviewed. All patients presented with myelopathy of varying magnitude. Mean patient age was 47 years. The mean follow-up period was 5.5 years. Median canal compromise of the cTDH was 66 %. cTDH were densely calcified in 7 (41 %), partially calcified in 6 (35 %) and soft in 4 (24 %) patients. Intradural extension of cTDH was noted in six patients (35 %). Benzels' modified myelopathy score of the Japanese Orthopedic Association was adjusted for the evaluation of thoracic myelopathy (mJOA) to assess functional outcomes. RESULTS: Successful removal of the offending cTDH was achieved in all patients. The overall mJOA Score improved from 7.9/13 to 11.1/13. Two patients with giant and densely calcified cTDH experienced a transient post-operative neurological decline. There was a statistically significant correlation between size of cTDH and intradural extension. CONCLUSION: Patients with myelopathy due to giant cTDH can be safely treated by the mini-thoracotomy approach. Postoperative neurological worsening and severe complications or incisional pain are rare. In contrast to complex posterior or thoracoscopic approaches, the mini-thoracotomy is technically straightforward and thus easy to learn for experienced spine surgeons. PMID- 26801196 TI - Computational postprocessing quantification of small bowel motility using magnetic resonance images in clinical practice: An initial experience. AB - PURPOSE: To study the feasibility and to gauge the potential clinical impact of quantifying small bowel motility using magnetic resonance imaging (MRI) in a larger population with a spectra of gastrointestinal conditions with impaired small bowel motility. MATERIALS AND METHODS: Data were gathered retrospectively from a cohort of 127 patients undergoing MR enterography (1.5 Tesla) in 2011. Cine motility sequences were processed with validated motility analysis software and a parametric motility map was generated. Regions of interests were drawn in the jejunum, ileum, and terminal ileum, and Jacobian standard deviation mean motility index' score (MIS) was calculated. Patients were divided into Crohn's disease (CD), ulcerative colitis, irritable bowel syndrome, and healthy subjects. RESULTS: In CD, terminal ileum motility was lower in comparison to healthy subjects (mean difference: -0.1052 arbitrary units, 95% confidence interval: 0.1981--0.0122, P = 0.018). Subgrouping of CD showed that the difference was recognized in patients with disease limited to the small bowel (mean difference: 0.1440 arbitrary units, 95% confidence interval: -0.2491--0.0389, P = 0.002). Visible dysmotility of terminal ileum on MRI reflected a reduced MIS compared with normal motility (0.22 +/- 0.09 and 0.33 +/- 0.15 arbitrary units, respectively, P = 0.043). Motility correlated negatively between ileum and age (P = 0.021), and between terminal ileum and C-reactive protein in ulcerative colitis (P = 0.031). CONCLUSION: Motility quantitation revealed a significant difference in motility of terminal ileum in patients with small bowel CD compared with healthy subjects, concording with visible dysmotility and inflammatory changes. J. Magn. Reson. Imaging 2016;44:277-287. PMID- 26801192 TI - Silk Fibroin Scaffolds for Urologic Tissue Engineering. AB - Urologic tissue engineering efforts have been largely focused on bladder and urethral defect repair. The current surgical gold standard for treatment of poorly compliant pathological bladders and severe urethral stricture disease is enterocystoplasty and onlay urethroplasty with autologous tissue, respectively. The complications associated with autologous tissue use and harvesting have led to efforts to develop tissue-engineered alternatives. Natural and synthetic materials have been used with varying degrees of success, but none has proved consistently reliable for urologic tissue defect repair in humans. Silk fibroin (SF) scaffolds have been tested in bladder and urethral repair because of their favorable biomechanical properties including structural strength, elasticity, biodegradability, and biocompatibility. SF scaffolds have been used in multiple animal models and have demonstrated robust regeneration of smooth muscle and urothelium. The pre-clinical data involving SF scaffolds in urologic defect repair are encouraging and suggest that they hold potential for future clinical use. PMID- 26801197 TI - Buttock Lifting with Polypropylene Strips. AB - BACKGROUND: The purpose of this study was to evaluate the results of gluteal suspension with polypropylene strips. PATIENTS AND METHODS: Ninety healthy female patients between the ages of 20 and 50 years (mean, 26 years), who wished to remodel their buttocks from December 2004 to February 2013 were studied retrospectively. All 90 patients were treated with 2 strips of polypropylene on each buttock using the following procedures: 27 (30 %) patients were suspended with polypropylene strips; 63 (70 %) patients were treated with tumescent liposuction in the sacral "V", lower back, supragluteal regions, and flanks to improve buttocks contour (aspirated volume of fat from 350 to 800 cc); 16 (18 %) patients underwent fat grafting in the subcutaneous and intramuscular layers (up to 300 cc in each buttock to increase volume); 5 (6 %) patients received implants to increase volume; and 4 (4.4 %) patients underwent removal and relocation of intramuscular gluteal implants to improve esthetics. RESULTS: Over an 8-year period, 90 female patients underwent gluteal suspension surgeries. Good esthetic results without complications were obtained in 75 of 90 (84 %) cases. Complications occurred in 15 of 90 (16.6 %) patients, including strip removal due to postoperative pain in 1 (1.1 %) patient, and seroma in both subgluteal sulci in 3 (3.3 %) patients. CONCLUSION: The results of this study performed in 90 patients over 8 years showed that the suspension with polypropylene strips performed as a single procedure or in combination with other cosmetic methods helps to enhance and lift ptosed gluteal and paragluteal areas. LEVEL OF EVIDENCE IV: This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26801198 TI - The Rising Burden of Hypertensive Renal Disease in Low-Income Countries: Is it Time to Take Action? PMID- 26801199 TI - Questioning REDD+ and the future of market-based conservation. PMID- 26801200 TI - Unique case of postural cholinergic urticaria induced by a standing position. PMID- 26801191 TI - Glucose Transporters at the Blood-Brain Barrier: Function, Regulation and Gateways for Drug Delivery. AB - Glucose transporters (GLUTs) at the blood-brain barrier maintain the continuous high glucose and energy demands of the brain. They also act as therapeutic targets and provide routes of entry for drug delivery to the brain and central nervous system for treatment of neurological and neurovascular conditions and brain tumours. This article first describes the distribution, function and regulation of glucose transporters at the blood-brain barrier, the major ones being the sodium-independent facilitative transporters GLUT1 and GLUT3. Other GLUTs and sodium-dependent transporters (SGLTs) have also been identified at lower levels and under various physiological conditions. It then considers the effects on glucose transporter expression and distribution of hypoglycemia and hyperglycemia associated with diabetes and oxygen/glucose deprivation associated with cerebral ischemia. A reduction in glucose transporters at the blood-brain barrier that occurs before the onset of the main pathophysiological changes and symptoms of Alzheimer's disease is a potential causative effect in the vascular hypothesis of the disease. Mutations in glucose transporters, notably those identified in GLUT1 deficiency syndrome, and some recreational drug compounds also alter the expression and/or activity of glucose transporters at the blood brain barrier. Approaches for drug delivery across the blood-brain barrier include the pro-drug strategy whereby drug molecules are conjugated to glucose transporter substrates or encapsulated in nano-enabled delivery systems (e.g. liposomes, micelles, nanoparticles) that are functionalised to target glucose transporters. Finally, the continuous development of blood-brain barrier in vitro models is important for studying glucose transporter function, effects of disease conditions and interactions with drugs and xenobiotics. PMID- 26801202 TI - In reference to Natural history and management of fanconi anemia patients with head and neck cancer: A 10-year follow-up. PMID- 26801201 TI - Microsomal PGE2 synthase-1 regulates melanoma cell survival and associates with melanoma disease progression. AB - COX-2 and its product PGE2 enhance carcinogenesis and tumor progression, which has been previously reported in melanoma. As most COX inhibitors cause much toxicity, the downstream microsomal PGE2 synthase-1 (mPGES1) is a consideration for targeting. Human melanoma TMAs were employed for testing mPGES1 protein staining intensity and percentage levels, and both increased with clinical stage; employing a different Stage III TMA, mPGES1 intensity (not percentage) associated with reduced patient survival. Our results further show that iNOS was also highly expressed in melanoma tissues with high mPGES1 levels, and iNOS-mediated NO promoted mPGES1 expression and PGE2 production. An mPGES1-specific inhibitor (CAY10526) as well as siRNA attenuated cell survival and increased apoptosis. CAY10526 significantly suppressed tumor growth and increased apoptosis in melanoma xenografts. Our findings support the value of a prognostic and predictive role for mPGES1, and suggest targeting this molecule in the PGE2 pathway as another avenue toward improving melanoma therapy. PMID- 26801203 TI - Characterization of differential pore-forming activities of ESAT-6 proteins from Mycobacterium tuberculosis and Mycobacterium smegmatis. AB - Mycobacterium tuberculosis ESAT-6 (MtbESAT-6) plays essential roles in pathogenesis. MtbESAT-6 exhibits a unique pore-forming activity (PFA) that is not found in its ortholog from non-pathogenic Mycobacterium smegmatis (MsESAT-6). Here, we characterized the differential PFAs and found that exchange of I25 H26/T25-A26 between two proteins reciprocally affected their PFAs. MtbESAT 6(IH/TA) had ~ 40% reduction, while MsESAT-6(TA/IH) fully acquired its activity similar to MtbESAT-6. Mutations of A17E, K38T, N67L or R74Q on MtbESAT-6(IH/TA) further reduced the activity, with MtbESAT-6(IH/TA-17) being the lowest. This study suggests I25-H26 as the pH-sensor essential for MsESAT-6 to fully acquire the activity, while multiple residues contributed to MtbESAT-6 PFA. PMID- 26801205 TI - An analysis of human papillomavirus testing and endocervical component on pap tests: A pilot study using the Roche Cobas((r)) assay. AB - INTRODUCTION: HPV is known to have a predilection for infecting the transformation zone (TZ). Endocervical cells (EC) on a Pap test (PT) indicate that the cervical TZ has been sampled. Earlier repeat testing of women lacking EC is of little value in further detecting disease, thus a sample without EC is not necessarily inadequate. Both HPV testing and PT can be performed using a single sample; however, few studies have investigated the relationship between HPV results and TZ sampling. MATERIALS AND METHODS: Specimens were collected following the ThinPrep((r)) liquid-based PT protocol. The Roche Cobas((r)) HPV test was performed on post-aliquot samples. Data was collected retrospectively on 500 patients: 250 consecutive cases of EC- and 250 of EC+ on PT. To maintain uniformity, we included only cases diagnosed as negative (NILM). We compared HPV test results within each category. As a positive control, five consecutive cases each of LSIL and HSIL were also reviewed. RESULTS: Of NILM cases, 11 of 250 EC+ cases and 14 of 250 EC- cases were positive for hrHPV. HPV 16 was present in 5 of 11 EC + cases and in 1 of 14 EC- cases. Of LSIL cases, 1 of 5 EC+ cases was positive for hrHPV, and 2 of 5 EC- cases were positive for hrHPV. Of HSIL cases, 5 of 5 EC+ cases were hrHPV+. In the time period studied, only one case of EC- HSIL was found, which was positive for hrHPV. DISCUSSION: Although our study did not prove a significant correlation between HPV testing results and EC on PT, more EC+ PTs were positive for HPV16 compared to EC- PTs. The absence of EC on PT does not appear to warrant re-testing for HPV infection, though larger studies are required to determine the significance of low HPV 16 in PT without EC. Diagn. Cytopathol. 2016;44:280-282. (c) 2016 Wiley Periodicals, Inc. PMID- 26801207 TI - Regorafenib-induced hand-foot skin reaction with striking epidermal dysmaturation - a new histopathological pattern associated with the use of multi-kinase inhibitors. PMID- 26801204 TI - Physiological and pathophysiological reactive oxygen species as probed by EPR spectroscopy: the underutilized research window on muscle ageing. AB - Reactive oxygen and nitrogen species (ROS and RNS) play crucial roles in triggering, mediating and regulating physiological and pathophysiological signal transduction pathways within the cell. Within the cell, ROS efflux is firmly controlled both spatially and temporally, making the study of ROS dynamics a challenging task. Different approaches have been developed for ROS assessment; however, many of these assays are not capable of direct identification or determination of subcellular localization of different ROS. Here we highlight electron paramagnetic resonance (EPR) spectroscopy as a powerful technique that is uniquely capable of addressing questions on ROS dynamics in different biological specimens and cellular compartments. Due to their critical importance in muscle functions and dysfunction, we discuss in some detail spin trapping of various ROS and focus on EPR detection of nitric oxide before highlighting how EPR can be utilized to probe biophysical characteristics of the environment surrounding a given stable radical. Despite the demonstrated ability of EPR spectroscopy to provide unique information on the identity, quantity, dynamics and environment of radical species, its applications in the field of muscle physiology, fatiguing and ageing are disproportionately infrequent. While reviewing the limited examples of successful EPR applications in muscle biology we conclude that the field would greatly benefit from more studies exploring ROS sources and kinetics by spin trapping, protein dynamics by site-directed spin labelling, and membrane dynamics and global redox changes by spin probing EPR approaches. PMID- 26801208 TI - Activity of tyrosol against single and mixed-species oral biofilms. AB - AIM: This study aimed to evaluate the effect of tyrosol on the formation of single and mixed biofilms of Candida albicans ATCC 10231, Candida glabrata ATCC 90030 and Streptococcus mutans ATCC 25175 formed on acrylic resin (AR) and hydroxyapatite (HA) surfaces. METHODS AND RESULTS: Single and mixed biofilms were formed on AR and HA in the presence of tyrosol at 50, 100 and 200 mmol l(-1), during 48 h. Next, antimicrobial activity was assessed through metabolic activity (XTT reduction assay) and the number of colony-forming units (CFUs). Scanning electron microscopy observations were performed in order to analyse biofilm structure. Tyrosol, mainly at 200 mmol l(-1), significantly decreased the metabolic activity and number of CFUs for all single and mixed-species biofilms formed on both surfaces. SEM images suggested cell damage caused by tyrosol. CONCLUSION: Tyrosol showed inhibitory effects against biofilms formed by important oral pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study showing the antibiofilm effect of tyrosol on Candida species and Strep. mutans in single and mixed cultures. These results may be useful in the development of topical therapies focused on preventing biofilm-associated oral diseases, such as denture stomatitis and dental caries. PMID- 26801206 TI - Metabolic regulation of triacylglycerol accumulation in the green algae: identification of potential targets for engineering to improve oil yield. AB - The great need for more sustainable alternatives to fossil fuels has increased our research interests in algal biofuels. Microalgal cells, characterized by high photosynthetic efficiency and rapid cell division, are an excellent source of neutral lipids as potential fuel stocks. Various stress factors, especially nutrient-starvation conditions, induce an increased formation of lipid bodies filled with triacylglycerol in these cells. Here we review our knowledge base on glycerolipid synthesis in the green algae with an emphasis on recent studies on carbon flux, redistribution of lipids under nutrient-limiting conditions and its regulation. We discuss the contributions and limitations of classical and novel approaches used to elucidate the algal triacylglycerol biosynthetic pathway and its regulatory network in green algae. Also discussed are gaps in knowledge and suggestions for much needed research both on the biology of triacylglycerol accumulation and possible avenues to engineer improved algal strains. PMID- 26801210 TI - Active immunization against vasoactive intestinal polypeptide decreases neuronal recruitment and inhibits reproduction in zebra finches. AB - Neurogenesis and neuronal recruitment occur in adult brains of many vertebrates, and the hypothesis is that these phenomena contribute to the brain plasticity that enables organisms to adjust to environmental changes. In mammals, vasoactive intestinal polypeptide (VIP) is known to have many neuroprotective properties, but in the avian brain, although widely distributed, its role in neuronal recruitment is not yet understood. In the present study we actively immunized adult zebra finches against VIP conjugated to KLH and compared neuronal recruitment in their brains, with brains of control birds, which were immunized against KLH. We looked at two forebrain regions: the nidopallium caudale (NC), which plays a role in vocal communication, and the hippocampus (HC), which is involved in the processing of spatial information. Our data demonstrate that active immunization against VIP reduces neuronal recruitment, inhibits reproduction, and induces molting, with no change in plasma prolactin levels. Thus, our observations suggest that VIP has a direct positive role in neuronal recruitment and reproduction in birds. J. Comp. Neurol. 524:2516-2528, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26801209 TI - Incidence of Adverse Events in Adults Undergoing Procedural Sedation in the Emergency Department: A Systematic Review and Meta-analysis. AB - OBJECTIVES: This was a systematic review and meta-analysis to evaluate the incidence of adverse events in adults undergoing procedural sedation in the emergency department (ED). METHODS: Eight electronic databases were searched, including MEDLINE, EMBASE, EBSCO, CINAHL, CENTRAL, Cochrane Database of Systematic Reviews, Web of Science, and Scopus, from January 2005 through 2015. Randomized controlled trials and observational studies of adults undergoing procedural sedation in the ED that reported a priori selected outcomes and adverse events were included. Meta-analysis was performed using a random-effects model and reported as incidence rates with 95% confidence intervals (CIs). RESULTS: The search yielded 2,046 titles for review. Fifty-five articles were eligible, including 9,652 procedural sedations. The most common adverse event was hypoxia, with an incidence of 40.2 per 1,000 sedations (95% CI = 32.5 to 47.9), followed by vomiting with 16.4 per 1,000 sedations (95% CI = 9.7 to 23.0) and hypotension with 15.2 per 1,000 sedations (95% CI = 10.7 to 19.7). Severe adverse events requiring emergent medical intervention were rare, with one case of aspiration in 2,370 sedations (1.2 per 1,000), one case of laryngospasm in 883 sedations (4.2 per 1,000), and two intubations in 3,636 sedations (1.6 per 1,000). The incidence of agitation and vomiting were higher with ketamine (164.1 per 1,000 and 170.0 per 1,000, respectively). Apnea was more frequent with midazolam (51.4 per 1,000), and hypoxia was less frequent in patients who received ketamine/propofol compared to other combinations. The case of laryngospasm was in a patient who received ketamine, and the aspiration and intubations were in patients who received propofol. When propofol and ketamine are combined, the incidences of agitation, apnea, hypoxia, bradycardia, hypotension, and vomiting were lower compared to each medication separately. CONCLUSIONS: Serious adverse events during procedural sedation like laryngospasm, aspiration, and intubation are exceedingly rare. Quantitative risk estimates are provided to facilitate shared decision-making, risk communication, and informed consent. PMID- 26801212 TI - Versatile method to generate multiple types of micropatterns. AB - Micropatterning techniques have become an important tool for the study of cell behavior in controlled microenvironments. As a consequence, several approaches for the creation of micropatterns have been developed in recent years. However, the diversity of substrates, coatings, and complex patterns used in cell science is so great that no single existing technique is capable of fabricating designs suitable for all experimental conditions. Hence, there is a need for patterning protocols that are flexible with regard to the materials used and compatible with different patterning strategies to create more elaborate setups. In this work, the authors present a versatile approach to micropatterning. The protocol is based on plasma treatment, protein coating, and a poly(L-lysine)-grafted poly(ethylene glycol) backfill step, and produces homogeneous patterns on a variety of substrates. Protein density within the patterns can be controlled, and density gradients of surface-bound protein can be formed. Moreover, by combining the method with microcontact printing, it is possible to generate patterns composed of three different components within one iteration of the protocol. The technique is simple to implement and should enable cell science labs to create a broad range of complex and highly specialized microenvironments. PMID- 26801211 TI - Integration of small RNAs, degradome and transcriptome sequencing in hyperaccumulator Sedum alfredii uncovers a complex regulatory network and provides insights into cadmium phytoremediation. AB - The hyperaccumulating ecotype of Sedum alfredii Hance is a cadmium (Cd)/zinc/lead co-hyperaccumulating species of Crassulaceae. It is a promising phytoremediation candidate accumulating substantial heavy metal ions without obvious signs of poisoning. However, few studies have focused on the regulatory roles of miRNAs and their targets in the hyperaccumulating ecotype of S. alfredii. Here, we combined analyses of the transcriptomics, sRNAs and the degradome to generate a comprehensive resource focused on identifying key regulatory miRNA-target circuits under Cd stress. A total of 87 721 unigenes and 356 miRNAs were identified by deep sequencing, and 79 miRNAs were differentially expressed under Cd stress. Furthermore, 754 target genes of 194 miRNAs were validated by degradome sequencing. A gene ontology (GO) enrichment analysis of differential miRNA targets revealed that auxin, redox-related secondary metabolism and metal transport pathways responded to Cd stress. An integrated analysis uncovered 39 pairs of miRNA targets that displayed negatively correlated expression profiles. Ten miRNA-target pairs also exhibited negative correlations according to a real time quantitative PCR analysis. Moreover, a coexpression regulatory network was constructed based on profiles of differentially expressed genes. Two hub genes, ARF4 (auxin response factor 4) and AAP3 (amino acid permease 3), which might play central roles in the regulation of Cd-responsive genes, were uncovered. These results suggest that comprehensive analyses of the transcriptomics, sRNAs and the degradome provided a useful platform for investigating Cd hyperaccumulation in S. alfredii, and may provide new insights into the genetic engineering of phytoremediation. PMID- 26801213 TI - Imaging of amyloid-beta in Alzheimer's disease transgenic mouse brains with ToF SIMS using immunoliposomes. AB - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) has been proven to successfully image different kinds of molecules, especially a variety of lipids, in biological samples. Proteins, however, are difficult to detect as specific entities with this method due to extensive fragmentation. To circumvent this issue, the authors present in this work a method developed for detection of proteins using antibody-conjugated liposomes, so called immunoliposomes, which are able to bind to the specific protein of interest. In combination with the capability of ToF-SIMS to detect native lipids in tissue samples, this method opens up the opportunity to analyze many different biomolecules, both lipids and proteins, at the same time, with high spatial resolution. The method has been applied to detect and image the distribution of amyloid-beta (Abeta), a biologically relevant peptide in Alzheimer's disease (AD), in transgenic mouse brain tissue. To ensure specific binding, the immunoliposome binding was verified on a model surface using quartz crystal microbalance with dissipation monitoring. The immunoliposome binding was also investigated on tissue sections with fluorescence microscopy, and compared with conventional immunohistochemistry using primary and secondary antibodies, demonstrating specific binding to Abeta. Using ToF-SIMS imaging, several endogenous lipids, such as cholesterol and sulfatides, were also detected in parallel with the immunoliposome-labeled Abeta deposits, which is an advantage compared to fluorescence microscopy. This method can thus potentially provide further information about lipid-protein interactions, which is important to understand the mechanisms of neurodegeneration in AD. PMID- 26801214 TI - Triplet-triplet energy transfer from chlorophylls to carotenoids in two antenna complexes from dinoflagellate Amphidinium carterae. AB - Room temperature transient absorption spectroscopy with nanosecond resolution was used to study quenching of the chlorophyll triplet states by carotenoids in two light-harvesting complexes of the dinoflagellate Amphidinium carterae: the water soluble peridinin-chlorophyll protein complex and intrinsic, membrane chlorophyll a-chlorophyll c2-peridinin protein complex. The combined study of the two complexes facilitated interpretation of a rather complicated relaxation observed in the intrinsic complex. While a single carotenoid triplet state was resolved in the peridinin-chlorophyll protein complex, evidence of at least two different carotenoid triplets was obtained for the intrinsic light-harvesting complex. Most probably, each of these carotenoids protects different chlorophylls. In both complexes the quenching of the chlorophyll triplet states by carotenoids occurs with a very high efficiency (~100%), and with transfer times estimated to be in the order of 0.1ns or even faster. The triplet-triplet energy transfer is thus much faster than formation of the chlorophyll triplet states by intersystem crossing. Since the triplet states of chlorophylls are formed during the whole lifetime of their singlet states, the apparent lifetimes of both states are the same, and observed to be equal to the carotenoid triplet state rise time (~5ns). PMID- 26801215 TI - Plant mitochondrial Complex I composition and assembly: A review. AB - In the mitochondrial inner membrane, oxidative phosphorylation generates ATP via the operation of several multimeric enzymes. The proton-pumping Complex I (NADH:ubiquinone oxidoreductase) is the first and most complicated enzyme required in this process. Complex I is an L-shaped enzyme consisting of more than 40 subunits, one FMN molecule and eight Fe-S clusters. In recent years, genetic and proteomic analyses of Complex I mutants in various model systems, including plants, have provided valuable insights into the assembly of this multimeric enzyme. Assisted by a number of key players, referred to as "assembly factors", the assembly of Complex I takes place in a sequential and modular manner. Although a number of factors have been identified, their precise function in mediating Complex I assembly still remains to be elucidated. This review summarizes our current knowledge of plant Complex I composition and assembly derived from studies in plant model systems such as Arabidopsis thaliana and Chlamydomonas reinhardtii. Plant Complex I is highly conserved and comprises a significant number of subunits also present in mammalian and fungal Complexes I. Plant Complex I also contains additional subunits absent from the mammalian and fungal counterpart, whose function in enzyme activity and assembly is not clearly understood. While 14 assembly factors have been identified for human Complex I, only two proteins, namely GLDH and INDH, have been established as bona fide assembly factors for plant Complex I. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt. PMID- 26801216 TI - Ebola survivors: not out of the woods yet. PMID- 26801217 TI - Novosphingobium piscinae sp. nov., isolated from a fish culture pond. AB - A bacterial strain designated SLH-16T was isolated from a fish culture pond in Taiwan and characterized using a polyphasic taxonomic approach. Cells of strain SLH-16T were Gram-stain-negative, aerobic, motile rods that were covered by large capsules and formed yellow colonies. Growth occurred at 20-40 degrees C (optimum, 37-40 degrees C), at pH 4.0-9.0 (optimum, pH 5.0-6.0) and with 0-0.5 % (w/v) NaCl (optimum, 0 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain SLH-16T belonged to the genus Novosphingobium and was related most closely to Novosphingobium taihuense T3-B9T with sequence similarity of 97.3 %. The major fatty acids (>10 %) of strain SLH-16T were C18 : 1omega7c, summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) and C16 : 0. The major 2-hydroxy fatty acid was C14 : 0 2-OH. The polar lipid profile consisted of phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidyldimethylethanolamine, sphingoglycolipid, phosphatidylcholine and several uncharacterized lipids. The major polyamine was spermidine. The major isoprenoid quinone was Q-10. The DNA G+C content was 65.2 mol%. The DNA-DNA hybridization value for strain SLH-16T and the type strain of N. taihuense was less than 43.2 %. Phenotypic characteristics of the novel strain also differed from those of the closest related species of the genus Novosphingobium. On the basis of the genotypic, chemotaxonomic and phenotypic data, strain SLH-16T represents a novel species in the genus Novosphingobium, for which the name Novosphingobium piscinae sp. nov. is proposed. The type strain is SLH-16T ( = BCRC 80888T = LMG 28418T = KCTC 42194T). PMID- 26801218 TI - A multiple kernel learning algorithm for drug-target interaction prediction. AB - BACKGROUND: Drug-target networks are receiving a lot of attention in late years, given its relevance for pharmaceutical innovation and drug lead discovery. Different in silico approaches have been proposed for the identification of new drug-target interactions, many of which are based on kernel methods. Despite technical advances in the latest years, these methods are not able to cope with large drug-target interaction spaces and to integrate multiple sources of biological information. RESULTS: We propose KronRLS-MKL, which models the drug target interaction problem as a link prediction task on bipartite networks. This method allows the integration of multiple heterogeneous information sources for the identification of new interactions, and can also work with networks of arbitrary size. Moreover, it automatically selects the more relevant kernels by returning weights indicating their importance in the drug-target prediction at hand. Empirical analysis on four data sets using twenty distinct kernels indicates that our method has higher or comparable predictive performance than 18 competing methods in all prediction tasks. Moreover, the predicted weights reflect the predictive quality of each kernel on exhaustive pairwise experiments, which indicates the success of the method to automatically reveal relevant biological sources. CONCLUSIONS: Our analysis show that the proposed data integration strategy is able to improve the quality of the predicted interactions, and can speed up the identification of new drug-target interactions as well as identify relevant information for the task. AVAILABILITY: The source code and data sets are available at www.cin.ufpe.br/~acan/kronrlsmkl/. PMID- 26801219 TI - Immune responses in multiple myeloma: role of the natural immune surveillance and potential of immunotherapies. AB - Multiple myeloma (MM) is a tumor of terminally differentiated B cells that arises in the bone marrow. Immune interactions appear as key determinants of MM progression. While myeloid cells foster myeloma-promoting inflammation, Natural Killer cells and T lymphocytes mediate protective anti-myeloma responses. The profound immune deregulation occurring in MM patients may be involved in the transition from a premalignant to a malignant stage of the disease. In the last decades, the advent of stem cell transplantation and new therapeutic agents including proteasome inhibitors and immunoregulatory drugs has dramatically improved patient outcomes, suggesting potentially key roles for innate and adaptive immunity in disease control. Nevertheless, MM remains largely incurable for the vast majority of patients. A better understanding of the complex interplay between myeloma cells and their immune environment should pave the way for designing better immunotherapies with the potential of very long term disease control. Here, we review the immunological microenvironment in myeloma. We discuss the role of naturally arising anti-myeloma immune responses and their potential corruption in MM patients. Finally, we detail the numerous promising immune-targeting strategies approved or in clinical trials for the treatment of MM. PMID- 26801220 TI - Epigenetic regulation of early neural fate commitment. AB - Early neural fate commitment is a key process in neural development and establishment of the central nervous system, and this process is tightly controlled by extrinsic signals, intrinsic factors, and epigenetic regulation. Here, we summarize the main findings regarding the regulatory network of epigenetic mechanisms that play important roles during early neural fate determination and embryonic development, including histone modifications, chromatin remodeling, DNA modifications, and RNA-level regulation. These regulatory mechanisms coordinate to play essential roles in silencing of pluripotency genes and activating key neurodevelopmental genes during cell fate commitment at DNA, histone, chromatin, and RNA levels. Moreover, we discuss the relationship between epigenetic regulation, signaling pathways, and intrinsic factors during early neural fate specification. PMID- 26801222 TI - Natural protein sequences are more intrinsically disordered than random sequences. AB - Most natural protein sequences have resulted from millions or even billions of years of evolution. How they differ from random sequences is not fully understood. Previous computational and experimental studies of random proteins generated from noncoding regions yielded inclusive results due to species dependent codon biases and GC contents. Here, we approach this problem by investigating 10,000 sequences randomized at the amino acid level. Using well established predictors for protein intrinsic disorder, we found that natural sequences have more long disordered regions than random sequences, even when random and natural sequences have the same overall composition of amino acid residues. We also showed that random sequences are as structured as natural sequences according to contents and length distributions of predicted secondary structure, although the structures from random sequences may be in a molten globular-like state, according to molecular dynamics simulations. The bias of natural sequences toward more intrinsic disorder suggests that natural sequences are created and evolved to avoid protein aggregation and increase functional diversity. PMID- 26801221 TI - Functional and pathological relevance of HERC family proteins: a decade later. AB - The HERC gene family encodes proteins with two characteristic domains in their sequence: the HECT domain and the RCC1-like domain (RLD). In humans, the HERC family comprises six members that can be divided into two groups based on their molecular mass and domain structure. Whereas large HERCs (HERC1 and HERC2) contain one HECT and more than one RLD, small HERCs (HERC3-6) possess single HECT and RLD domains. Accumulating evidence shows the HERC family proteins to be key components of a wide range of cellular functions, including neurodevelopment, DNA damage repair, cell growth and immune response. Considering the significant recent advances made regarding HERC functionality, an updated review summarizing the progress is greatly needed at 10 years since the last HERC review. We provide an integrated view of HERC function and go into detail about its implications for several human diseases such as cancer and neurological disorders. PMID- 26801223 TI - Association between single nucleotide polymorphisms (SNPs) of XRCC2 and XRCC3 homologous recombination repair genes and ovarian cancer in Polish women. AB - The variability, perceived in DNA repair genes, may be of clinical importance for evaluation of the risk of occurrence of a given type of cancer, its prophylactics and therapy. The aim of the present work was to evaluate associations between the risk of ovarian cancer and polymorphisms in the genes, encoding for two key proteins of homologous recombination: XRCC2 Arg188His (c. 563 G>A; rs3218536) and XRCC3 Thr241Met (c. 722 C>T; rs861539). The study consisted of 700 patients with ovarian cancer and 700 healthy subjects. Analysis of the gene polymorphisms was performed using PCR-RFLP (restriction length fragment polymorphism). We found a statistically significant increase of the 188His allele frequency (OR=4.01; 95% CI=3.40-4.72; p<.0001) of XRCC2 in ovarian cancer compared to healthy controls. There were no differences in the genotype and allele distributions and odds ratios of the XRCC3 Thr241Met polymorphism between patient and control groups. Association of these genetic polymorphisms with histological grading showed increased XRCC2 188Arg/His (OR=33.0; 95% CI=14.51-75.05; p<.0001) and 188His/His genotypes (OR=9.37; 95% CI=4.79-18.32; p<.0001) and XRCC3 241Thr/Met (OR=24.28; 95% CI=12.38-47.61; p<.0001) and 241Met/Met genotype frequencies (OR=17.00; 95% CI=8.42-34.28; p<.0001) in grading 1 (G1) as well as 188His (OR=2.78; 95% CI=2.11 3.69; p<.0001) and 241Met allele overrepresentation (OR=2.59; 95% CI=2.08-3.22; p<.0001) in G1 ovarian patients. Finally, with clinical FIGO staging under evaluation, an increase in XRCC2 188His/His homozygote and 188Arg/His heterozygote frequencies in staging I (SI) and XRCC3 Thr/Met heterozygote frequencies in SI was observed. The obtained results indicate that XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms may be positively associated with the incidence of ovarian carcinoma in the population of Polish women. PMID- 26801224 TI - Are complement-fixing antibodies against denatured HLA antigens clinically relevant? PMID- 26801225 TI - Towards preparedness for PrEP: PrEP awareness and acceptability among MSM at high risk of HIV transmission who use sociosexual media in four Celtic nations: Scotland, Wales, Northern Ireland and The Republic of Ireland: an online survey. AB - OBJECTIVE: To assess the awareness and acceptability of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) and use sociosexual media at high risk of HIV infection in four Celtic nations. DESIGN: Cross-sectional study. METHODS: Online self-complete survey of 386 HIV-negative/status unknown MSM who reported condomless anal intercourse (CAI) with >=2 men in the last year, recruited from gay sociosexual media. RESULTS: One-third (34.5%, 132/386) of the participants were aware of PrEP but over half (58.5%, 226/356) reported that they would be willing to use PrEP if it were available to them. Only men who regularly tested for HIV every 6 months (adjusted OR 2.89, 95% CI 1.54 to 5.42) were more likely to be aware of PrEP. PrEP acceptability was only associated with reporting >=5 CAI partners (OR 2.04, 95% CI 1.2 to 3.46) in the last year. CONCLUSIONS: Low levels of PrEP awareness were reported across these Celtic nations. Only one third of high-risk MSM had heard of PrEP but over one-half would be willing to take a daily pill to prevent HIV infection. Sociodemographic factors, commercial gay scene proximity and social network use were unrelated to considering PrEP use. However, those reporting most CAI partners were more likely to consider PrEP use. PMID- 26801226 TI - A 'test and treat' prevention strategy in Australia requires innovative HIV testing models: a cohort study of repeat testing among 'high-risk' men who have sex with men. AB - OBJECTIVES: HIV diagnoses among men who have sex with men (MSM) in several high income countries, including Australia, have increased substantially over recent years. Australia, in line with global prevention strategies, has emphasised a 'test and treat' HIV prevention strategy which relies on timely detection of HIV through frequent testing by those at risk. We examined trends in repeat testing among MSM defined as 'high-risk' according to Australian testing guidelines. METHODS: HIV test records from MSM attending high caseload clinics in Melbourne 2007-2013 and classified as high-risk were analysed. Binary outcomes of 'test within 3 months' and 'test within 6 months' were assigned to tests within individuals' panel of records. Negative binomial regressions assessed trends in overall HIV testing and returning within 3 and 6 months. Annualised proportions of return tests (2007-2012) were compared using two-sample z tests. RESULTS: Across 18 538 tests among 7117 high-risk MSM attending primary care clinics in Melbourne (2007-2013), the number of annual HIV tests increased (p<0.01). Between 2007 and 2012 annualised proportions of tests with a subsequent test within 3 and 6 months also increased (p<0.01); however, by 2012 only 36.4% and 15.1% of tests were followed by another test inside 6 and 3 months, respectively. CONCLUSIONS: Repeat testing among high-risk MSM in Australia remains unacceptably low, with recent modest increases in testing unlikely to deliver meaningful prevention impact. Removing known barriers to HIV testing is needed to maximise the potential benefit of test and treat-based HIV prevention. PMID- 26801227 TI - Acquired alexithymia following damage to the anterior insula. AB - Alexithymia is a subclinical condition characterized by impaired awareness of one's emotional states, which has profound effects on mental health and social interaction. Despite the clinical significance of this condition, the neurocognitive impairment(s) that lead to alexithymia remain unclear. Recent theoretical models suggest that impaired anterior insula (AI) functioning might be involved in alexithymia, but conclusive evidence for this hypothesis is lacking. We measured alexithymia levels in a large sample of brain-injured patients (N=129) and non-brain-injured control participants (N=33), to determine whether alexithymia can be acquired after pronounced damage to the AI. Alexithymia levels were first analysed as a function of group, with patients separated into four groups based on AI damage: patients with >15% damage to AI, patients with <15% damage to AI, patients with no damage to AI, and healthy controls. An ANOVA revealed that alexithymia levels varied across groups (p=0.009), with >15% AI damage causing higher alexithymia relative to all other groups (all p<0.01). Next, a multiple linear regression model was fit with the degree of damage to AI, the degree of damage to a related region (the anterior cingulate cortex, ACC), and the degree of damage to the whole brain as predictor variables, and alexithymia as the dependent variable. Critically, increased AI damage predicted increased alexithymia after controlling for the other two regressors (ACC damage; total lesion volume). Collectively, our results suggest that pronounced AI damage causes increased levels of alexithymia, providing critical evidence that this region supports emotional awareness. PMID- 26801228 TI - Evidence for dissociable effects of handedness and consistency of hand preference in allocation of attention and movement planning: An EEG investigation. AB - We studied the potentially dissociable effects of handedness and consistency of hand preference on allocation of attention and movement planning. EEG was recorded from an equally balanced group of left- and right-handed participants with consistent or inconsistent hand preference. The participants viewed photos of graspable objects and responded to the direction of an arrow that was overlaid on the object 1000ms after object onset. Attention-related ERPs elicited between 100 and 250ms after object onset were primarily modulated by the participants' handedness. On the other hand, ERPs related to late movement planning processes were modulated only by the consistency of hand preference. Our results suggest that the effects of the consistency of hand preference could be dissociated from those of handedness, the former influencing movement planning processes and the latter more related to allocation of attention. PMID- 26801230 TI - Retraction: Pharmacologic Inactivation of Kinase Suppressor of Ras1 Sensitizes Epidermal Growth Factor Receptor and Oncogenic Ras-Dependent Tumors to Ionizing Radiation Treatment. PMID- 26801231 TI - Sleep Difficulty and Disease in a Cohort of Very Old Women. AB - OBJECTIVE: The objective of this study was to investigate the association between chronic diseases and sleep difficulty in older women. METHOD: A total of 10,721 women from The Australian Longitudinal Study on Women's Health, aged 70 to 75 years at baseline (1996), who answered sleep questionnaire data over 15 years follow-up, were surveyed. Longitudinal sleep difficulty class was regressed on baseline diseases. RESULTS: Arthritis and heart disease were the strongest predictors of sleep difficulty; odds ratios for belonging to the greatest sleep difficulty class were 2.27 (95% confidence interval [CI] = [1.98, 2.61]) and 1.8 (95% CI [1.5, 2.16], respectively. Bronchitis/emphysema, osteoporosis, asthma, diabetes, and hypertension also predicted greater sleep difficulty. CONCLUSION: Older women diagnosed with the aforementioned significant diseases may also be at greater risk of sleep difficulty. These women may need counseling or treatment for their sleep difficulty, to prevent depression, cognitive function decline, falls, frailty, and increased mortality, as well as greater risk of nursing home placement, well known to be reinforced by sleep trouble, and the associated health care costs and societal impacts poor sleep quality has for older adults. PMID- 26801229 TI - A meta-analysis of fMRI decoding: Quantifying influences on human visual population codes. AB - Information in the human visual system is encoded in the activity of distributed populations of neurons, which in turn is reflected in functional magnetic resonance imaging (fMRI) data. Over the last fifteen years, activity patterns underlying a variety of perceptual features and objects have been decoded from the brains of participants in fMRI scans. Through a novel multi-study meta analysis, we have analyzed and modeled relations between decoding strength in the visual ventral stream, and stimulus and methodological variables that differ across studies. We report findings that suggest: (i) several organizational principles of the ventral stream, including a gradient of pattern granulation and an increasing abstraction of neural representations as one proceeds anteriorly; (ii) how methodological choices affect decoding strength. The data also show that studies with stronger decoding performance tend to be reported in higher-impact journals, by authors with a higher h-index. As well as revealing principles of regional processing, our results and approach can help investigators select from the thousands of design and analysis options in an empirical manner, to optimize future studies of fMRI decoding. PMID- 26801232 TI - The feasibility of a train-the-trainer approach to end of life care training in care homes: an evaluation. AB - BACKGROUND: The ABC End of Life Education Programme trained approximately 3000 care home staff in End of Life (EoL) care. An evaluation that compared this programme with the Gold Standards Framework found that it achieved equivalent outcomes at a lower cost with higher levels of staff satisfaction. To consolidate this learning, a facilitated peer education model that used the ABC materials was piloted. The goal was to create a critical mass of trained staff, mitigate the impact of staff turnover and embed EoL care training within the organisations. The aim of the study was to evaluate the feasibility of using a train the trainer (TTT) model to support EoL care in care homes. METHODS: A mixed method design involved 18 care homes with and without on-site nursing across the East of England. Data collection included a review of care home residents' characteristics and service use (n = 274), decedents' notes n = 150), staff interviews (n = 49), focus groups (n = 3), audio diaries (n = 28) and observations of workshops (n = 3). RESULTS: Seventeen care homes participated. At the end of the TTT programme 28 trainers and 114 learners (56% of the targeted number of learners) had been trained (median per home 6, range 0-13). Three care homes achieved or exceeded the set target of training 12 learners. Trainers ranged from senior care staff to support workers and administrative staff. Results showed a positive association between care home stability, in terms of leadership and staff turnover, and uptake of the programme. Care home ownership, type of care home, size of care home, previous training in EoL care and resident characteristics were not associated with programme completion. Working with facilitators was important to trainers, but insufficient to compensate for organisational turbulence. Variability of uptake was also linked to management support, programme fit with the trainers' roles and responsibilities and their opportunities to work with staff on a daily basis. CONCLUSION: When there is organisational stability, peer to peer approaches to skills training in end of life care can, with expert facilitation, cascade and sustain learning in care homes. PMID- 26801233 TI - Total thyroidectomy as primary surgical management for thyroid disease: surgical therapy experience from 5559 thyroidectomies in a less-developed region. AB - BACKGROUND: The objective of this study was to evaluate the safety of total thyroidectomy for thyroid disorders and summarise the treatment experience in a less-developed region. METHODS: This was a retrospective observational cohort study using the computerised database of the First Affiliated Hospital of Harbin Medical University. All consecutive thyroidectomy patients from 2003 to 2014 were included in this study. Demographics, surgical procedure, diagnoses, morbidity and mortality were retrospectively reviewed. RESULTS: There were a total of 714 men and 4845 women in this study, with a mean age of 55 (range 9-87) years. A total of 4632 patients underwent total thyroidectomy for primary surgical treatment, and 189 patients previously underwent partial thyroidectomy. A total of 56.2% of the patients had multinodular goitre, including 12.23% who were thyrotoxic. Graves' disease and Hashimoto's disease were diagnosed in 2.82 and 7.23% of the patients, respectively. Papillary thyroid cancer was identified in 1336 patients, 44.99% of whom had papillary microcarcinoma. The total prevalence of permanent complications of first-time and secondary surgeries was 0.35 and 7.41%, respectively. During thyroid surgery, 945 patients underwent parathyroid autotransplantation. CONCLUSIONS: Initial total thyroidectomy can be safely performed for both benign and malignant thyroid diseases in a less-developed region. The morbidity of a secondary surgical procedure after subtotal thyroidectomy is significantly high compared to first-time surgery. PMID- 26801234 TI - Double-Blind Comparison of Ultrasonic and Conventional Osteotomy in Terms of Early Postoperative Edema and Ecchymosis. AB - BACKGROUND: Edema and ecchymosis are common complications of rhinoplasty. Modifications to osteotomy may reduce edema and ecchymosis and ameliorate postoperative discomfort in patients who undergo rhinoplasty. OBJECTIVES: The authors performed osteotomy with conventional instruments or with an ultrasonic device and compared these methods with respect to the severities of ecchymosis and edema in the early postoperative period. METHODS: Fifty-six patients who underwent primary rhinoplasty with medial oblique, low-to-high internal osteotomy performed conventionally or with an ultrasonic device were evaluated in a prospective study. Photographs of the patients on postoperative days 3 and 7 were scored for ecchymosis and edema by 2 physicians who did not perform the operations and were blinded to the osteotomy procedure. RESULTS: Ecchymosis scores on postoperative days 3 and 7 and edema scores on postoperative day 3 were significantly higher for the 22 patients who underwent conventional osteotomy than for the 34 patients who underwent ultrasonic osteotomy, as scored by both examiners. Edema scores on postoperative day 7 were significantly higher for conventional than for ultrasonic osteotomy as assessed by 1 examiner but were not significantly different as determined by the other examiner. CONCLUSIONS: The results of this comparative study suggest that rhinoplasty with ultrasonic osteotomy is associated with less edema and ecchymosis in the early postoperative period than is rhinoplasty with conventional osteotomy. LEVEL OF EVIDENCE: 3 Therapeutic. PMID- 26801235 TI - The existence of standard-biased mortality ratios due to death certificate misclassification - a simulation study based on a true story. AB - BACKGROUND: Mortality statistics are used to compare health status of populations; optimally, they base on individual death certificates. However, determining cause of death is error-prone. E.g. cardiovascular disease (CVD) death determination is characterized by sensitivity (SE) and specificity (SP) lower than 85%. Furthermore, differential misclassification may be present in case of homogenous target populations. We investigate the bias of standardized mortality ratios (SMR), based on real-world data. METHODS: CVD mortality of 6378 ethnic German repatriates was assessed and the SMR calculated. Non-differential age-dependent misclassification was introduced into data by scenarios of equal SE and SP in a range of 0.7 to 0.85. The bias between originally reported and actual SMR was calculated for each pair of values. Additionally, four differential misclassification scenarios were simulated, reflecting two extreme scenarios of both quality criteria varied in the cohort but fixed to either higher or lower in the reference, and two scenarios of crossed criteria values. RESULTS: In case of non-differential misclassification the bias is always towards the null hypothesis. The lowest bias was 13.5% (SE, SP = 0.85 constantly), the maximum bias was 40% (SP = 0.7). However, in case of differential misclassification the observed SMR can be on the wrong track. If SP is high but SE low in the cohort, negative bias up to -10% can occur. In case SE is low but SP is high in the reference, the bias remains always positive. In the opposite case plus SP is high in the cohort, the bias can reach -30%. CONCLUSION: SMR values are always biased due to the diagnostic test character of death determination. In majority of epidemiological studies the bias should be towards the null-hypothesis (non differential misclassification). However, caution is needed in case of differential misclassification, possibly experienced in studies on homogenous subgroups, and in large prospective cohorts with specifically trained personnel. PMID- 26801236 TI - A statistical analysis of cervical auscultation signals from adults with unsafe airway protection. AB - BACKGROUND: Aspiration, where food or liquid is allowed to enter the larynx during a swallow, is recognized as the most clinically salient feature of oropharyngeal dysphagia. This event can lead to short-term harm via airway obstruction or more long-term effects such as pneumonia. In order to non invasively identify this event using high resolution cervical auscultation there is a need to characterize cervical auscultation signals from subjects with dysphagia who aspirate. METHODS: In this study, we collected swallowing sound and vibration data from 76 adults (50 men, 26 women, mean age 62) who underwent a routine videofluoroscopy swallowing examination. The analysis was limited to swallows of liquid with either thin (<5 cps) or viscous (~300 cps) consistency and was divided into those with deep laryngeal penetration or aspiration (unsafe airway protection), and those with either shallow or no laryngeal penetration (safe airway protection), using a standardized scale. After calculating a selection of time, frequency, and time-frequency features for each swallow, the safe and unsafe categories were compared using Wilcoxon rank-sum statistical tests. RESULTS: Our analysis found that few of our chosen features varied in magnitude between safe and unsafe swallows with thin swallows demonstrating no statistical variation. We also supported our past findings with regard to the effects of sex and the presence or absence of stroke on cervical ausculation signals, but noticed certain discrepancies with regards to bolus viscosity. CONCLUSIONS: Overall, our results support the necessity of using multiple statistical features concurrently to identify laryngeal penetration of swallowed boluses in future work with high resolution cervical auscultation. PMID- 26801237 TI - Bentall procedure: quarter century of clinical experiences of a single surgeon. AB - BACKGROUND: We retrospectively analyzed 25 years of experiences with the button Bentall procedure in patients with aortic root pathologies. Even though this procedure has become widespread, there are only a few very long term follow-ups available in the clinical literature, especially regarding single surgeon results. METHODS: Between 1988 and 2013, a total of 147 patients underwent the Bentall procedure by the same surgeon. Among them there were 62 patients with Marfan syndrome. At the time of the surgery the mean age was 46.5 +/- 17.6 years. The impact of surgical experience on long-term survival was evaluated using a cumulative sum analysis chart. RESULTS: The Kaplan-Meier estimated overall survival rates for the 147 patients were 91.8 +/- 2.3 %, 84.3 +/- 3.1 %, 76.3 +/- 4.9 % and 59.5 +/- 10.7 % at 1,5,10 and 20 years, respectively. Multivariate Cox regression analysis identified EuroSCORE II over 3 % (OR 4.245, 95 % CI, 1.739 10.364, p = 0.002), acute indication (OR 2.942, 95 % CI, 1.158-7.480, p = 0.023), use of deep hypothermic circulatory arrest (OR 3.267, 95 % CI, 1.283-8.323, p = 0.013), chronic kidney disease (OR 6.865, 95 % CI, 1.339-35.189, p = 0.021) and early complication (OR 3.134, 95 % CI, 1.246-7.883, p = 0.015) as significant risk factors for the late overall death. The survival rate for freedom from early complication was 94.3 +/- 2.2 %, 88.0 +/- 3.3 %, 82.9 +/- 4.7 % and 69.2 +/- 8.4 % at 1,5,10 and 20 years. The main pathological findings of the aortic wall were cystic medial degeneration in 75 %, fibrosis in 6 %, atherosclerosis in 13 % and no pathological alteration in 6 % of the samples. The overall survival rate was significantly lower in patients operated in first 15 years compared to patients operated in the last decade (log-rank p = 0.011). CONCLUSION: According to our long-term follow-up the Bentall operation provides an appropriate functional result by resolving the lesions of the ascending aorta. Based on our results, 25 30 operations done is necessary to gain such a level of confidence and experience to aquire better results on long-term survival. In addition, we discussed that there were no co-morbidities affecting on the survival of Marfan patients and prophylactic aortic root replacement ensures a longer survival among patients with Marfan syndrome. PMID- 26801238 TI - Temporal Associations Between Sleep and Physical Activity Among Overweight/Obese Youth. AB - OBJECTIVE: Examine average interindividual and temporal intraindividual associations between time of sleep onset (sleep onset), total sleep time (TST), and minutes in moderate-to-very-vigorous physical activity per hour (MVPA/h) among overweight/obese youth. METHODS: Overweight/obese youth (n = 134; 7-12 years) wore an accelerometer for 16+ hr/day, 5-7 days, which provided daily objective estimates of MVPA/h, TST, and sleep onset. RESULTS: Multilevel models revealed an intraindividual effect of TST, such that nights with longer TST preceded less MVPA/h during the midnight-to-midnight monitoring period; a significant random effect qualified this relationship. Average interindividual TST did not predict mean MVPA/h, whereas sleep onset significantly predicted mean MVPA/h. CONCLUSIONS: Later time of sleep onset (as opposed to TST) was the strongest predictor of group-level decreased physical activity. At the individual level, longer TST than usual predicted less MVPA/h than usual. Results suggest the need for more person-centered research and a greater focus on sleep timing among youth. PMID- 26801239 TI - Validation of a Rapid and Sensitive UPLC-MS-MS Method Coupled with Protein Precipitation for the Simultaneous Determination of Seven Pyrethroids in 100 uL of Rat Plasma by Using Ammonium Adduct as Precursor Ion. AB - United States Environmental Protection Agency has recommended estimating pyrethroids' risk using cumulative exposure. For cumulative risk assessment, it would be useful to have a bioanalytical method for quantification of one or several pyrethroids simultaneously in a small sample volume to support toxicokinetic studies. Therefore, in the present study, a simple, sensitive and high-throughput ultraperformance liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous analysis of seven pyrethroids (fenvalerate, fenpropathrin, bifenthrin, lambda-cyhalothrin, cyfluthrin, cypermethrin and deltamethrin) in 100 uL of rat plasma. A simple single-step protein precipitation method was used for the extraction of target compounds. The total chromatographic run time of the method was 5 min. The chromatographic system used a Supelco C18 column and isocratic elution with a mobile phase consisting of methanol and 5 mM ammonium formate in the ratio of 90 : 10 (v/v). Mass spectrometer (API 4000) was operated in multiple reaction monitoring positive-ion mode using the electrospray ionization technique. The calibration curves were linear in the range of 7.8-2,000 ng/mL with correlation coefficients of >= 0.99. All validation parameters such as precision, accuracy, recovery, matrix effect and stability met the acceptance criteria according to the regulatory guidelines. The method was successfully applied to the toxicokinetic study of cypermethrin in rats. To the best of our knowledge, this is the first LC MS-MS method for the simultaneous analysis of pyrethroids in rat plasma. This validated method with minimal modification can also be utilized for forensic and clinical toxicological applications due to its simplicity, sensitivity and rapidity. PMID- 26801240 TI - Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation but has no effect on bone formation in the delayed-type hypersensitivity arthritis (DTHA) model. AB - BACKGROUND: The aims of the present study were to determine the relationship between bone destruction and bone formation in the delayed-type hypersensitivity arthritis (DTHA) model and to evaluate the effect of receptor activator of nuclear factor kappaB ligand (RANKL) blockade on severity of arthritis, bone destruction, and bone formation. METHODS: DTHA was induced in C57BL/6 mice. Inflammation, erosive joint damage, and new bone formation were semiquantitatively scored by histology. Osteoclast activity was assessed in vivo, and messenger RNA (mRNA) expression of mediators of bone destruction and bone formation were analyzed by mRNA deep sequencing. Serum concentrations of tartrate resistant acid phosphatase 5b, carboxy-terminal telopeptide I (CTX-I), matrix metalloproteinase 3 (MMP3), and serum amyloid P component (SAP) were determined by enzyme-linked immunosorbent assay. Anti-RANKL monoclonal antibody treatment was initiated at the time of immunization. RESULTS: Bone destruction (MMP3 serum levels, cathepsin B activity, and RANKL mRNA) peaked at day 3 after arthritis induction, followed by a peak in cartilage destruction and bone erosion on day 5 after arthritis induction. Periarticular bone formation was observed from day 10. Induction of new bone formation indicated by enhanced Runx2, collagen X, osteocalcin, MMP2, MMP9, and MMP13 mRNA expression was observed only between days 8 and 11. Anti-RANKL treatment resulted in a modest reduction in paw and ankle swelling and a reduction of serum levels of SAP, MMP3, and CTX-I. Destruction of the subchondral bone was significantly reduced, while no effect on bone formation was seen. CONCLUSIONS: Anti-RANKL treatment prevents joint destruction but does not prevent new bone formation in the DTHA model. Thus, although occurring sequentially during the course of DTHA, bone destruction and bone formation are apparently not linked in this model. PMID- 26801241 TI - Associations between self-perception of weight, food choice intentions, and consumer response to calorie information: a retrospective investigation of public health center clients in Los Angeles County before the implementation of menu labeling regulation. AB - BACKGROUND: Although obesity continues to rise and remains a great public health concern in the U.S., a number of important levers such as self-perception of weight and calorie postings at point-of-purchase in restaurants are still not well-characterized in the literature, especially for low-income and minority groups in Los Angeles County (LAC). To study this gap, we examined the associations of self-perception of weight (as measured by body weight discrepancy) with food choice intentions and consumer response to calorie information among low-income adults residing in LAC during the pre-menu labeling regulation era. METHODS: Descriptive and multivariable logistic regression analyses were performed to examine the aforementioned associations utilizing data from the 2007-2008 Calorie and Nutrition Information Survey (CNIS). The CNIS was a local health department study of 639 low-income adults recruited from five large, multi-purpose public health centers in LAC. RESULTS: Survey participants who reported that their desired weight was less than their current weight (versus desired weight the same as current weight) had (i) higher odds of intending to select lower-calorie foods under the scenario that calorie information was available at point-of-purchase (aOR = 2.0; 95 % CI: 1.0-3.9); and (ii) had higher odds of reporting that it is "very important" to have these calorie postings on food items in grocery stores (aOR = 3.1; 95 % CI: 0.90-10.7) and in fast-food restaurants (aOR = 3.4; 95 % CI: 1.0-11.4). CONCLUSIONS: Self-perception of weight was found to be associated with the intention to select lower-calorie foods under the scenario that calorie information was available at point-of purchase. Future public health efforts to support menu labeling implementation should consider these and other findings to inform consumer education and communications strategies that can be tailored to assist restaurant patrons with this forthcoming federal law. PMID- 26801242 TI - Suboptimal culture conditions induce more deviations in gene expression in male than female bovine blastocysts. AB - BACKGROUND: Since the development of in vitro embryo production in cattle, different supplements have been added to culture media to support embryo development, with serum being the most popular. However, the addition of serum during embryo culture can induce high birthweights and low viability in calves (Large Offspring Syndrome). Analysis of global gene expression in bovine embryos produced under different conditions can provide valuable information to optimize culture media for in vitro embryo production. RESULTS: We used RNA sequencing to examine the effect of in vitro embryo production, in either serum-containing or serum-free media, on the global gene expression pattern of individual bovine blastocysts. Compared to in vivo derived embryos, embryos produced in serum containing medium had five times more differentially expressed genes than embryos produced in serum-free conditions (1109 vs. 207). Importantly, in vitro production in the presence of serum appeared to have a different impact on the embryos according to their sex, with male embryos having three times more genes differentially expressed than their female counterparts (1283 vs. 456). On the contrary, male and female embryos produced in serum-free conditions showed the same number (191 vs. 192) of genes expressed differentially; however, only 44 of those genes were common in both comparisons. The pathways affected by in vitro production differed depending on the type of supplementation. For example, embryos produced in serum-containing conditions had a lower expression of genes related to metabolism while embryos produced in serum-free conditions showed aberrations in genes involved in lipid metabolism. CONCLUSIONS: Serum supplementation had a major impact on the gene expression pattern of embryos, with male embryos being the most affected. The transcriptome of embryos produced in serum-free conditions showed a greater resemblance to that of in vivo derived embryos, although genes involved in lipid metabolism were altered. Male embryos appeared to be most affected by suboptimal in vitro culture, i.e. in the presence of serum. PMID- 26801243 TI - Meaning of self-management from the perspective of individuals with traumatic spinal cord injury, their caregivers, and acute care and rehabilitation managers: an opportunity for improved care delivery. AB - BACKGROUND: The trend of decreasing length of stay in rehabilitation facilities has led to individuals with spinal cord injury (SCI) entering the community with unmet needs and fewer self-care skills to prevent secondary complications. The implementation of a self-management program for individuals with SCI for the management of these complex needs, including secondary complications, may be one option to fill these care gaps. A greater understanding of the meaning of self management may facilitate the development of a tailored self-management program in this population. Thus, the current research aims to understand the meaning of self-management in traumatic SCI from the perspectives of individuals with traumatic SCI and their caregivers as well as acute care/trauma and rehabilitation managers. METHODS: A descriptive qualitative approach was used. Semi-structured telephone interviews were conducted with 26 individuals with traumatic SCI, their family members/caregivers, and managers from acute care/trauma and rehabilitation centres. Inductive thematic analysis was applied. RESULTS: The meaning of self-management in SCI related to two overarching themes of internal and external responsibility attribution and revealed differences between the meaning of self-management in SCI among individuals with traumatic SCI and their caregivers versus managers. Overall, the meaning of self-management among the SCI and caregiver participants related principally to internal responsibility attribution. For the manager participants, the meaning of self management was much narrower and the overarching theme of internal responsibility attribution that was observed among the SCI-caregiver dyads was not as widely expressed by this group. CONCLUSIONS: Interventions that are co-created by users and health care professionals are associated with positive physical and mental health outcomes. Thus, the understanding of self-management from these varying perspectives could be applied to the development of a tailored self-management program that is relevant to individuals with traumatic SCI and their caregivers. This may involve the development of a program that uses some of the structure of traditional chronic disease self-management programs, in accordance with the beliefs held by the managers, but also incorporates elements of wellness/health promotion interventions, in accordance with the beliefs held by the SCI and caregiver participants. PMID- 26801244 TI - Finding harmony so the music plays on: pragmatic trial design considerations to promote organizational sustainment of an empirically-supported behavior therapy. AB - BACKGROUND: Pragmatic trials of empirically-supported behavior therapies may inform clinical and policy decisions concerning therapy sustainment. This retrospective trial design paper describes and discusses pragmatic features of a hybrid type III implementation/effectiveness trial of a contingency management (CM) intervention at an opioid treatment program. Prior reporting (Hartzler et al., J Subst Abuse Treat 46:429-438, 2014; Hartzler, Subst Abuse Treat Prev Policy 10:30, 2015) notes success in recruiting program staff for voluntary participation, durable impacts of CM training on staff-level outcomes, provisional setting implementation of the intervention, documentation of clinical effectiveness, and post-trial sustainment of CM. METHODS/DESIGN: Six pragmatic design features, and both scientific and practical bases for their inclusion in the trial, are presented: (1) a collaborative intervention design process, (2) voluntary recruitment of program staff for therapy training and implementation, (3) serial training outcome assessments, with quasi-experimental staff randomization to either single or multiple baseline assessment conditions, (4) designation of a 90-day period immediately after training in which the setting implemented the intervention on a provisional basis, (5) inclusive patient eligibility for receipt of the CM intervention, and (6) designation of two staff as local implementation leaders to oversee clinical/administrative issues in provisional implementation. DISCUSSION: Each pragmatic trial design feature is argued to have contributed to sustainment of CM. Contributions implicate the building of setting proprietorship for the CM intervention, culling of internal staff expertise in its delivery, iterative use of assessment methods that limited setting burden, documentation of setting-specific clinical effectiveness, expanded penetration of CM among staff during provisional implementation, and promotion of setting self-reliance in the oversight of sustainable implementation procedures. It is hoped this discussion offers ideas for how to impact local clinical and policy decisions via effective behavior therapy dissemination. PMID- 26801245 TI - MRI pallidal signal in children exposed to manganese in drinking water. AB - BACKGROUND: Manganese (Mn) can have neurotoxic effects upon overexposure. We previously reported poorer cognitive and motor development in children exposed to Mn through drinking water, suggesting possible neurotoxic effects from Mn in water. Hyperintensity in the globus pallidus (GP) on T1-weighted magnetic resonance imaging (MRI) indicates excessive brain Mn accumulation. Previous studies have reported GP hyperintensity related to Mn exposure in occupationally exposed individuals. However, no study has used MRI in children exposed to Mn in drinking water and who show no sign of overt intoxication. OBJECTIVE: To examine MRI signal intensity in the GP in children exposed to contrasted levels of Mn in drinking water. METHODS: We enrolled 13 children exposed to low Mn concentration in water and 10 children (ages 9-15 years) with high concentration (median of 1 and 145MUg/L, respectively). We calculated three MRI T1 indexes: (i) standard pallidal index (PI) using frontal white matter as reference; (ii) PI using pericranial muscles as reference; and (iii) T1 relaxation time. Each MRI index was compared between exposure groups, and with respect to the estimated Mn intake from water consumption. RESULTS: The standard PI did not differ between Mn exposure groups. However, children in the group with high water-Mn concentration had significantly lower pericranial muscles PI than those with lower exposure and, accordingly, higher T1 relaxation time. Mn intake from water consumption was not correlated with the standard PI, but was significantly related to the pericranial muscles PI and T1 relaxation time. Motor performance was significantly lower in the high-exposure group. CONCLUSION: We observed lower signal intensity in the GP of children with higher exposure to Mn from drinking water. This result stands in contrast to previous MRI reports showing GP hyperintensity with greater Mn exposure. Differences in exposure pathways are discussed as a potential explanation for this discrepancy. PMID- 26801246 TI - miR-508-3p concordantly silences NFKB1 and RELA to inactivate canonical NF-kappaB signaling in gastric carcinogenesis. AB - BACKGROUND: NF-kappaB signaling pathway plays an important role in gastric carcinogenesis. The basic expression and functional role of NFKB1 and RELA (components of canonical NF-kappaB pathway) in gastric cancer (GC) have not been well elucidated. In this study, the role of NFKB1 and RELA in gastric tumorigenesis will be investigated and their regulation by microRNAs (miRNAs) will be deeply explored. METHODS: The mRNA and protein expression of NFKB1 and RELA were investigated by qRT-PCR and Western blot in GC cell lines and primary tumors. The functional roles of NFKB1 and RELA in GC were demonstrated by MTT proliferation assay, monolayer colony formation, cell invasion and migration, cell cycle analysis and in vivo study through siRNA mediated knockdown. Identification of NFKB1 as a direct target of tumor suppressor miRNA miR-508-3p was achieved by expression regulation assays together with dual luciferase activity experiments. RESULTS: NFKB1 and RELA were up-regulated in GC cell lines and primary tumors compared with normal gastric epithelium cells and their upregulation correlation with poor survival in GC. siRNA mediated knockdown of NFKB1 or RELA exhibited anti-oncogenic effect both in vitro and in vivo. NFKB1 was further revealed to be a direct target of miR-508-3p in gastric tumorigenesis and their expression showed negative correlation in primary GC samples. miR-508 3p was down-regulated in GC cells compared with normal gastric epithelium samples and its ectopic expression in GC cell lines also exerts tumor suppressor function. NFKB1 re-expression was found to partly abolish the tumor-suppressive effect of miR-508-3p in GC. CONCLUSION: All these findings supports that canonical NF-kappaB signaling pathway is activated in GC at least by the inactivation of miR-508-3p and this might have therapeutic potential in GC treatment. PMID- 26801248 TI - Divergence of Antiangiogenic Activity and Hepatotoxicity of Different Stereoisomers of Itraconazole. AB - PURPOSE: Itraconazole is a triazole antifungal drug that has recently been found to inhibit angiogenesis. Itraconazole is a relatively well-tolerated drug but shows hepatotoxicity in a small subset of patients. Itraconazole contains three chiral centers and the commercial itraconazole is composed of four cis stereoisomers (named IT-A, IT-B, IT-C, and IT-D). We sought to determine whether the stereoisomers of itraconazole might differ in their antiangiogenic activity and hepatotoxicity. EXPERIMENTAL DESIGN: We assessed in vitro antiangiogenic activity of itraconazole and each stereoisomer using human umbilical vein endothelial cell (HUVEC) proliferation and tube formation assays. We also determined their hepatotoxicity using primary human hepatocytes in vitro and a mouse model in vivo Mouse Matrigel plug and tumor xenograft models were used to evaluate in vivo antiangiogenic and antitumor activities of the stereoisomers. RESULTS: Of the four stereoisomers contained in commercial itraconazole, we found that IT-A (2S,4R,2'R) and IT-C (2S,4R,2'S) were more potent for inhibition of angiogenesis than IT-B (2R,4S,2'R) and IT-D (2R,4S,2'S). Interestingly, IT-A and IT-B were more hepatotoxic than IT-C and IT-D. In mouse models, IT-C showed more potent antiangiogenic/antitumor activity with lower hepatotoxicity compared with itraconazole and IT-A. CONCLUSIONS: These results demonstrate the segregation of influence of stereochemistry at different positions of itraconazole on its antiangiogenic activity and hepatotoxicity, with the 2 and 4 positions affecting the former and the 2' position affecting the latter. They also suggest that IT-C may be superior to the racemic mixture of itraconazole as an anticancer drug candidate due to its lower hepatotoxicity and improved antiangiogenic activity. Clin Cancer Res; 22(11); 2709-20. (c)2016 AACR. PMID- 26801247 TI - Phase I Study of Veliparib (ABT-888) Combined with Cisplatin and Vinorelbine in Advanced Triple-Negative Breast Cancer and/or BRCA Mutation-Associated Breast Cancer. AB - PURPOSE: Cisplatin is synergistic with vinorelbine and the PARP inhibitor veliparib, and has antineoplastic activity in triple-negative breast cancer (TNBC) and BRCA mutation-associated breast cancer. This phase I study assessed veliparib with cisplatin and vinorelbine. EXPERIMENTAL DESIGN: A 3+3 dose escalation design evaluated veliparib administered twice daily for 14 days with cisplatin (75 mg/m(2) day 1) and vinorelbine (25 mg/m(2) days 1, 8) every 21 days, for 6 to 10 cycles, followed by veliparib monotherapy. Pharmacokinetics, measurement of poly(ADP-ribose) in peripheral blood mononuclear cells, and preliminary efficacy were assessed. IHC and gene-expression profiling were evaluated as potential predictors of response. RESULTS: Forty-five patients enrolled in nine dose cohorts plus five in an expansion cohort at the highest dose level and recommended phase II dose, 300 mg twice daily. The MTD of veliparib was not reached. Neutropenia (36%), anemia (30%), and thrombocytopenia (12%) were the most common grade 3/4 adverse events. Best overall response for 48 patients was radiologic response with 9-week confirmation for 17 (35%; 2 complete, 15 partial), and stable disease for 21 (44%). Germline BRCA mutation presence versus absence was associated with 6-month progression-free survival [PFS; 10 of 14 (71%) vs. 8 of 27 (30%), mid-P = 0.01]. Median PFS for all 50 patients was 5.5 months (95% confidence interval, 4.1-6.7). CONCLUSIONS: Veliparib at 300 mg twice daily combined with cisplatin and vinorelbine is well tolerated with encouraging response rates. A phase II randomized trial is planned to assess veliparib's contribution to cisplatin chemotherapy in metastatic TNBC and BRCA mutation-associated breast cancer. Clin Cancer Res; 22(12); 2855-64. (c)2016 AACR. PMID- 26801251 TI - Duchenne muscular dystrophy: Ringo to the rescue? PMID- 26801249 TI - Alternative cleavage and polyadenylation in spermatogenesis connects chromatin regulation with post-transcriptional control. AB - BACKGROUND: Most mammalian genes display alternative cleavage and polyadenylation (APA). Previous studies have indicated preferential expression of APA isoforms with short 3' untranslated regions (3'UTRs) in testes. RESULTS: By deep sequencing of the 3' end region of poly(A) + transcripts, we report widespread shortening of 3'UTR through APA during the first wave of spermatogenesis in mouse, with 3'UTR size being the shortest in spermatids. Using genes without APA as a control, we show that shortening of 3'UTR eliminates destabilizing elements, such as U-rich elements and transposable elements, which appear highly potent during spermatogenesis. We additionally found widespread regulation of APA events in introns and exons that can affect the coding sequence of transcripts and global activation of antisense transcripts upstream of the transcription start site, suggesting modulation of splicing and initiation of transcription during spermatogenesis. Importantly, genes that display significant 3'UTR shortening tend to have functions critical for further sperm maturation, and testis-specific genes display greater 3'UTR shortening than ubiquitously expressed ones, indicating functional relevance of APA to spermatogenesis. Interestingly, genes with shortened 3'UTRs tend to have higher RNA polymerase II and H3K4me3 levels in spermatids as compared to spermatocytes, features previously known to be associated with open chromatin state. CONCLUSIONS: Our data suggest that open chromatin may create a favorable cis environment for 3' end processing, leading to global shortening of 3'UTR during spermatogenesis. mRNAs with shortened 3'UTRs are relatively stable thanks to evasion of powerful mRNA degradation mechanisms acting on 3'UTR elements. Stable mRNAs generated in spermatids may be important for protein production at later stages of sperm maturation, when transcription is globally halted. PMID- 26801253 TI - Adaptive evolution and metabolic engineering of a cellobiose- and xylose- negative Corynebacterium glutamicum that co-utilizes cellobiose and xylose. AB - BACKGROUND: An efficient microbial cell factory requires a microorganism that can utilize a broad range of substrates to economically produce value-added chemicals and fuels. The industrially important bacterium Corynebacterium glutamicum has been studied to broaden substrate utilizations for lignocellulose-derived sugars. However, C. glutamicum ATCC 13032 is incapable of PTS-dependent utilization of cellobiose because it has missing genes annotated to beta-glucosidases (bG) and cellobiose-specific PTS permease. RESULTS: We have engineered and evolved a cellobiose-negative and xylose-negative C. glutamicum that utilizes cellobiose as sole carbon and co-ferments cellobiose and xylose. NGS-genomic and DNA microarray transcriptomic analysis revealed the multiple genetic mutations for the evolved cellobiose-utilizing strains. As a result, a consortium of mutated transporters and metabolic and auxiliary proteins was responsible for the efficient cellobiose uptake. Evolved and engineered strains expressing an intracellular bG showed a better rate of growth rate on cellobiose as sole carbon source than did other bG secreting or bG-displaying C. glutamicum strains under aerobic culture. Our strain was also capable of co-fermenting cellobiose and xylose without a biphasic growth, although additional pentose transporter expression did not enhance the xylose uptake rate. We subsequently assessed the strains for simultaneous saccharification and fermentation of cellulosic substrates derived from Canadian Ponderosa Pine. CONCLUSIONS: The combinatorial strategies of metabolic engineering and adaptive evolution enabled to construct C. glutamicum strains that were able to co-ferment cellobiose and xylose. This work could be useful in development of recombinant C. glutamicum strains for efficient lignocellulosic biomass conversion to produce value-added chemicals and fuels. PMID- 26801254 TI - Expert opinion of mediastinal lymph node positions from an intrabronchial view. AB - BACKGROUND: The knowledge of the mediastinal lymph node positions from an intrabronchial view was important for conventional transbronchial needle aspiration (TBNA). The introduction of endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) changed the focus from the intrabronchial landmarks to the real life ultrasound images. However when all EBUS reachable lymph nodes are evaluated (mapping), the knowledge of the intrabronchial positions is crucial. The objective of this study was to present a new expert opinion map from an intrabronchial perspective validated by an interobserver variation analysis. METHODS: Physicians who had performed more than 30 EBUS-TBNA were included. They marked areas for optimal TBNA sampling on standardized pictures from an intrabronchial perspective. Areas marked by more than 3 of the 14 experts who had performed more than 1000 EBUS provided the data for the map. The map was validated among the experts and the agreement was compared to the agreement among less experienced physicians. RESULTS: There was high agreement (>80%) among the experts in lymph node positions 4 L, 7, 10 L, 11R and 11 L. The agreement for 4R and 10R was low (<70%). The agreement among the most experienced physicians was significantly higher than the less experienced physicians in station 10 L (92% vs. 50%, p:0.01). CONCLUSIONS: It was possible to present a new map of expert opinion for optimal sampling positions in lymph node stations 4 L, 4R, 7, 10 L, 11R and 11 L. All positions except 4R had high agreement. No area was covered by more than 3 of the 14 experts in station 10R. PMID- 26801296 TI - A Maximum Likelihood Approach to Correlational Outlier Identification. AB - This article introduces a maximum likelihood approach to correlational outlier identification and compares it to the Mahalanobis D squared and Comrey D using a Monte Carlo simulation. The performance measures used were the hit rate and bias in correlation estimates resulting from the application of each technique. The results indicate that identification performance depends heavily on the nature of the correlational outliers and the performance measure used, but that the maximum likelihood approach exhibits the most robust performance across conditions. PMID- 26801297 TI - Cross-Validation for Choosing the Number of Important Components in Principal Component Analysis. AB - A cross-validation method (Krzanowski, 1987) for selecting the significant components from a principal components analysis is described. Some properties of this method are discussed, and parallels are drawn with other related methods in covariance structure modelling. Some comparisons among the methods are effected empirically on two data sets which have been analyzed previously in the literature, and the implications of the analyses for these sets are briefly discussed. PMID- 26801298 TI - A Generalizability Analysis of Subjective Personality Assessments in the Stumptail Macaque and the Zebra Finch. AB - Psychometric findings are reported from two studies concerning the construct validity, temporal stability, and interrater reliability of the latent common factors underlying subjective assessments by human raters of personality traits in two nonhuman animal species: (a) the Stumptail macaque (Maraca arctoides), a cercopithecine monkey; and (b) the Zebra finch (Poephila guttata), an estrildid songbird. Because most theories of animal personality have historically implied that certain personality constructs should be relatively universal across taxa, parallel analyses of similar data are reported for two phylogenetically distant species of subject using the same psychometric methods. Each of the samples was drawn from a socially-housed colony of the same species: that of macaques consisted of 5 mature adult fem ales and 8 of their adult offspring and that of finches consisted of 5 adult individuals. A modified version of the 1978 Stevenson-Hinde and Zunz (SHZ) list of personality items was applied to the macaques at various times during the eight years from 1980-1988 and to the finches during 1992. This study also used the three SHZ scales - Confident, Excitable, and Sociable - originally derived from principal components. Generalizability analyses were used to assess the construct validity, temporal stability, and interrater reliability of the hypothesized factors. Both Stumptail macaques and Zebra finches manifest measurable personality factors that are highly valid across multiple items, stable across multiple years, and reliable across multiple raters. The same model fits both species, as predicted by theory. The construct validity of the factors is slightly higher for the finches than for the macaques, although the interrater reliability is somewhat lower. This study illustrates how generalizability analysis can be used to test prespecified confirmatory factor models when the number of individual subjects is quite small. PMID- 26801299 TI - Multidimensional Representation of Decision-making in Chronic Schizophrenics. AB - We administered all paired comparisons of eight gambling stimuli to samples of inpatient schizophrenics, outpatient schizophrenics, and a comparison group of first-degree relatives. A matrix of pairwise preferences was elicited from each subject, and decomposed into a binary matrix indicating stimulus choice, and an unsigned dissimilarity matrix representing strength of preference. These matrices were analyzed using maximum likelihood multidimensional scaling methods, resulting in a representation of subjects and stimuli in an n-dimensional decision space. Results suggest that choice behavior of all groups was determined almost exclusively by the expected value of the stimuli, with no significant differences among the groups. Strength of preference was influenced by expected value for only the comparison group, with a much larger unsystematic component among the schizophrenic groups. PMID- 26801300 TI - Testing the Hypothesis of Independence Between Two Sets of Variates. AB - The article compares five methods for testing the hypothesis of independence between two sets of variates. Two of the methods are new and based on straightforward generalizations of two robust measures of covariance recently appearing in the literature. Simulation results indicate that both of the new methods provide reasonably accurate control over the probability of a Type I error even with a relatively small sample size and extreme departure from normality. The usual likelihood ratio test is already known to be unsatisfactory, and results in this article indicate that the control over the probability of a Type I error can be even worse than indicated by previous investigations. The new procedures are based on robust measures reflecting the linear association between two random variables, so they provide an important alternative to rank based methods. PMID- 26801301 TI - The Effects of Within-group Covariance Structure on Recovery in Cluster Analysis: I. The Bivariate Case. AB - In a preliminary investigation, two Monte Carlo studies investigated the effects of within-group covariance structure on subgroup recovery by I0 hierarchical clustering methods. Data sets were 100 bivariate observations from two subgroups. Study 1 manipulated subgroup size, within-group correlation, within-group variance, and distance between centroids. Negative within-group correlation yielded much poorer recovery for all clustering methods. In addition, clustering method interacted with within-group variance. Study 2 manipulated subgroup size, within-group correlation, direction of the vector separating subgroup centroids, and distance between subgroup centroids. Superior recovery was associated with within-group correlation that matched the direction of subgroup separation. Results are interpreted according to the weakness of Euclidean distance as a measure of (dis)similarity. PMID- 26801302 TI - Multivariate Structural Modeling of Plasticity in Fluid Intelligence of Aged Adults. AB - This article is concerned with modeling the structure of cognitive intervention effects in adult intellectual development. Within the Cattell-Horn (Cattell, 1971 ; Horn, 1970, 1982) theory of fluid and crystallized intelligence, the ability of older adults to improve their performance on fluid intelligence tests, with or without tutor-guided instruction in test-relevant cognitive skills, is examined using multidimensional longitudinal structural equation models. The models reflect in some of their parameters substantively interesting aspects of temporal change at the ability level, and are applied to data from a two-group cognitive intervention study of plasticity in fluid intelligence of older adults (Baltes, Dittmann-Kohli, & Kliegl, 1986). Training effects are found in the experimental group that are more salient than the practice/experience effects in the control group; both types of effects are maintained over a six month testing period. Exploration of the nature of the practice effects in the control group reveals patterns of test performance improvement that are equivalent to those in the experimental group, as reflected in the interrelationships among initial ability levels and maximal improvements at the ability dimensions relative to initial status. The results suggest (a) considerable plasticity in adult intellectual functioning, and (b) that healthy aged adults may be capable - based on experience with repeatedly presented measures - to markedly improve their performance on fluid intelligence tests by capitalizing on interdependencies between fluid subabilities. PMID- 26801303 TI - Monocytes increase human cardiac myofibroblast-mediated extracellular matrix remodeling through TGF-beta1. AB - Following myocardial infarction (MI), cardiac myofibroblasts remodel the extracellular matrix (ECM), preventing mechanical complications. However, prolonged myofibroblast activity leads to dysregulation of the ECM, maladaptive remodeling, fibrosis, and heart failure (HF). Chronic inflammation is believed to drive persistent myofibroblast activity; however, the mechanisms are unclear. We assessed the influence of peripheral blood monocytes on human cardiac myofibroblast activity in a three-dimensional (3D) ECM microenvironment. Human cardiac myofibroblasts isolated from surgical biopsies of the right atrium and left ventricle were seeded into 3D collagen matrices. Peripheral blood monocytes were isolated from healthy human donors and cocultured with myofibroblasts. Monocytes increased myofibroblast activity measured by collagen gel contraction (baseline: 57.6 +/- 5.9% vs. coculture: 65.2 +/- 7.1% contraction; P < 0.01) and increased local ECM remodeling quantified by confocal microscopy. Under coculture conditions that allow indirect cellular interaction via paracrine factors but prevent direct cell-cell contact, monocytes had minimal effects on myofibroblast activity (17.9 +/- 11.1% vs. 6.4 +/- 7.0% increase, respectively; P < 0.01). When cells were cultured under direct contact conditions, multiplex analysis of the coculture media revealed an increase in the paracrine factors TGF-beta1 and matrix metalloproteinase 9 compared with baseline (122.9 +/- 10.1 pg/ml and 3,496.0 +/- 190.4 pg/ml, respectively, vs. 21.5 +/- 16.3 pg/ml and 183.3 +/- 43.9 pg/ml; P < 0.001). TGF-beta blockade abolished the monocyte-induced increase in cardiac myofibroblast activity. These data suggest that direct cell-cell interaction between monocytes and cardiac myofibroblasts stimulates TGF-beta mediated myofibroblast activity and increases remodeling of local matrix. Peripheral blood monocyte interaction with human cardiac myofibroblasts stimulates myofibroblast activity through release of TGF-beta1. These data implicate inflammation as a potential driver of cardiac fibrosis. PMID- 26801304 TI - Targeted delivery of human iPS-ECs overexpressing IL-8 receptors inhibits neointimal and inflammatory responses to vascular injury in the rat. AB - Interleukin-8 (IL8) is highly expressed by injured arteries in a variety of diseases and is a chemoattractant for neutrophils which express IL8 receptors IL8RA and RB (IL8RA/B) on their membranes. Neutrophils interact with the damaged endothelium and initiate an inflammatory cascade at the site of injury. We have generated a novel translational targeted cell therapy for acute vascular injury using adenoviral vectors to overexpress IL8RA/B and green fluorescent protein (GFP) on the surface of endothelial cells (ECs) derived from human induced pluripotent stem cells (HiPS-IL8RA/B-ECs). We hypothesize that HiPS-IL8RA/B-ECs transfused intravenously into rats with balloon injury of the carotid artery will target to the injured site and compete with neutrophils, thus inhibiting inflammation and neointima formation. Young adult male Sprague-Dawley rats underwent balloon injury of the right carotid artery and received intravenous transfusion of saline vehicle, 1.5 * 10(6) HiPS-ECs, 1.5 * 10(6) HiPS-Null-ECs, or 1.5 * 10(6) HiPS-IL8RA/B-ECs immediately after endoluminal injury. Tissue distribution of HiPS-IL8RA/B-ECs was analyzed by a novel GFP DNA qPCR method. Cytokine and chemokine expression and leukocyte infiltration were measured in injured and uninjured arteries at 24 h postinjury by ELISA and immunohistochemistry, respectively. Neointimal, medial areas, and reendothelialization were measured 14 days postinjury. HiPS-IL8RA/B-ECs homed to injured arteries, inhibited inflammatory mediator expression and inflammatory cell infiltration, accelerated reendothelialization, and attenuated neointima formation after endoluminal injury while control HiPS-ECs and HiPS-Null-ECs did not. HiPS-IL8RA/B-ECs transfused into rats with endoluminal carotid artery injury target to the injured artery and provide a novel strategy to treat vascular injury. PMID- 26801306 TI - Responses of cardiac natriuretic peptides after paroxysmal supraventricular tachycardia: ANP surges faster than BNP and CNP. AB - Atrial natriuretic peptide (ANP) secretion increases after 30 min of paroxysmal supraventricular tachycardia (PSVT). Whether this phenomenon also applies to brain or C-type natriuretic peptides (BNP or CNP) remains unknown. Blood samples of 18 patients (41 +/- 11 yr old; 4 men) with symptomatic PSVT and normal left ventricular systolic function (ejection fraction 65 +/- 6%) were collected from the coronary sinus (CS) and the femoral artery (FA) before and 30 min after the induction, and 30 min after the termination of PSVT. The results showed that the ANP levels rose steeply after the PSVT and then reduced at 30 min after the termination (baseline vs. post-PSVT vs. posttermination: CS: 34.0 +/- 29.6 vs. 74.1 +/- 42.3 vs. 46.1 +/- 32.9; FA: 5.9 +/- 3.24 vs. 28.2 +/- 20.7 vs. 10.0 +/- 4.6 pg/ml; all P < 0.05). In contrast, compared with ANP, the increases of BNP and CNP in CS after the PSVT were less sharp, but continued to rise after the termination of tachycardia (BNP, 10.2 +/- 6.4 vs. 11.3 +/- 7.1 vs. 11.8 +/- 7.9; CNP, 4.5 +/- 1.2 vs. 4.9 +/- 1.4 vs. 5.0 +/- 1.4 pg/ml; all P < 0.05). The rise of BNP and CNP in FA was similarly less sharp after the PSVT and remained stationary after the termination. PSVT exerted differential effects on cardiac natriuretic peptide levels. ANP increased greater after a 30-min induced PSVT, but dropped faster after termination of PSVT, compared with BNP and CNP. PMID- 26801307 TI - Myocyte repolarization modulates myocardial function in aging dogs. AB - Studies of myocardial aging are complex and the mechanisms involved in the deterioration of ventricular performance and decreased functional reserve of the old heart remain to be properly defined. We have studied a colony of beagle dogs from 3 to 14 yr of age kept under a highly regulated environment to define the effects of aging on the myocardium. Ventricular, myocardial, and myocyte function, together with anatomical and structural properties of the organ and cardiomyocytes, were evaluated. Ventricular hypertrophy was not observed with aging and the structural composition of the myocardium was modestly affected. Alterations in the myocyte compartment were identified in aged dogs, and these factors negatively interfere with the contractile reserve typical of the young heart. The duration of the action potential is prolonged in old cardiomyocytes contributing to the slower electrical recovery of the myocardium. Also, the remodeled repolarization of cardiomyocytes with aging provides inotropic support to the senescent muscle but compromises its contractile reserve, rendering the old heart ineffective under conditions of high hemodynamic demand. The defects in the electrical and mechanical properties of cardiomyocytes with aging suggest that this cell population is an important determinant of the cardiac senescent phenotype. Collectively, the delayed electrical repolarization of aging cardiomyocytes may be viewed as a critical variable of the aging myopathy and its propensity to evolve into ventricular decompensation under stressful conditions. PMID- 26801305 TI - Emerging role of hydrogen sulfide-microRNA crosstalk in cardiovascular diseases. AB - Despite an obnoxious smell and toxicity at a high dose, hydrogen sulfide (H2S) is emerging as a cardioprotective gasotransmitter. H2S mitigates pathological cardiac remodeling by regulating several cellular processes including fibrosis, hypertrophy, apoptosis, and inflammation. These encouraging findings in rodents led to initiation of a clinical trial using a H2S donor in heart failure patients. However, the underlying molecular mechanisms by which H2S mitigates cardiac remodeling are not completely understood. Empirical evidence suggest that H2S may regulate signaling pathways either by directly influencing a gene in the cascade or interacting with nitric oxide (another cardioprotective gasotransmitter) or both. Recent studies revealed that H2S may ameliorate cardiac dysfunction by up- or downregulating specific microRNAs. MicroRNAs are noncoding, conserved, regulatory RNAs that modulate gene expression mostly by translational inhibition and are emerging as a therapeutic target for cardiovascular disease (CVD). Few microRNAs also regulate H2S biosynthesis. The inter-regulation of microRNAs and H2S opens a new avenue for exploring the H2S-microRNA crosstalk in CVD. This review embodies regulatory mechanisms that maintain the physiological level of H2S, exogenous H2S donors used for increasing the tissue levels of H2S, H2S-mediated regulation of CVD, H2S-microRNAs crosstalk in relation to the pathophysiology of heart disease, clinical trials on H2S, and future perspectives for H2S as a therapeutic agent for heart failure. PMID- 26801308 TI - Early cardiac changes induced by a hypercaloric Western-type diet in "subclinical" obesity. AB - "Obesity cardiomyopathy" effects have been widely described; however, the specific contribution of metabolic changes and altered adipokine secretion are still uncharacterized. Moreover, a diagnosis based on body mass index might not be the most accurate to identify increased adiposity and its outcomes. In this study, we aimed to determine the impact of a Western-type diet [hypercaloric diet (HCD)] ingestion on biventricular structure and function, as well as the metabolic and endocrine changes that occur before the establishment of overt obesity. Wistar rats were fed for 6 wk with a regular diet or HCD. At the end of the protocol, metabolic tests, cardiac structure, and functional evaluation were performed, and blood and tissue samples collected to perform histological, molecular biology, and functional studies. The animals that ingested the HCD presented increased adiposity and larger adipocyte cross-sectional area, but similar body weight compared with the regular diet group. At the cardiac level, HCD induced biventricular cardiomyocyte hypertrophy, fibrosis, increased stiffness, and impaired relaxation. Galectin-3 plasma expression was likewise elevated in the same animals. The nutritional modulation also altered the secretory pattern of the adipose tissue, originating a proinflammatory systemic environment. In this study, we observed that before "clinical" overweight or frank obesity is established, the ingestion of a HCD-induced cardiac remodeling manifests by increased biventricular stiffness and diastolic dysfunction. The mechanism triggering the cardiac alterations appears to be the proinflammatory environment promoted by the adipose tissue dysfunction. Furthermore, galectin-3, a profibrotic molecule, might be a potential biomarker for the myocardial alterations promoted by the HCD before overweight or obesity. PMID- 26801309 TI - ERK1/2 MAPK signaling in hypothalamic paraventricular nucleus contributes to sympathetic excitation in rats with heart failure after myocardial infarction. AB - Brain MAPK signaling pathways are activated in heart failure (HF) induced by myocardial infarction and contribute to augmented sympathetic nerve activity. We tested whether decreasing ERK1/2 (also known as p44/42 MAPK) signaling in the hypothalamic paraventricular nucleus (PVN), a forebrain source of presympathetic neurons, would reduce the upregulation of sympathoexcitatory mediators in the PVN and augmented sympathetic nerve activity in rats with HF. Sprague-Dawley rats underwent left anterior descending coronary artery ligation to induce HF, with left ventricular dysfunction confirmed by echocardiography. One week after coronary artery ligation or sham operation, small interfering (si)RNAs targeting ERK1/2 or a nontargeting control siRNA was microinjected bilaterally into the PVN. Experiments were conducted 5-7 days later. Confocal images revealed reduced phosphorylated ERK1/2 immunofluorescence in the PVN of HF rats treated with ERK1/2 siRNAs compared with HF rats treated with control siRNA. Western blot analysis confirmed significant reductions in both total and phosphorylated ERK1/2 in the PVN of HF rats treated with ERK1/2 siRNAs along with reduced expression of renin-angiotensin system components and inflammatory mediators. HF rats treated with ERK1/2 siRNAs also had reduced PVN neuronal excitation (fewer Fos-related antigen-like-immunoreactive neurons), lower plasma norepinephrine levels, and improved peripheral manifestations of HF compared with HF rats treated with control siRNAs. These results demonstrate that ERK1/2 signaling in the PVN plays a pivotal role in mediating sympathetic drive in HF induced by myocardial infarction and may be a novel target for therapeutic intervention. PMID- 26801310 TI - Oscillatory lower body negative pressure impairs task related functional hyperemia in healthy volunteers. AB - Neurovascular coupling refers to the link between an increase in neural activity in response to a task and an increase in cerebral blood flow denoted "functional hyperemia." Recent work on postural tachycardia syndrome indicated that increased oscillatory cerebral blood flow velocity (CBFv) was associated with reduced functional hyperemia. We hypothesized that a reduction in functional hyperemia could be causally produced in healthy volunteers by using oscillations in lower body negative pressure (OLBNP) to force oscillations in CBFv. CBFv was measured by transcranial Doppler ultrasound of the left middle cerebral artery. We used passive arm flexion applied during eight periodic 60-s flexion/60-s relaxation epochs to produce 120-s periodic changes in functional hyperemia (at 0.0083 Hz). We used -30 mmHg of OLBNP at 0.03, 0.05, and 0.10 Hz, the range for cerebral autoregulation, and measured spectral power of CBFv at all frequencies. Arm flexion power performed without OLBNP was compared with arm flexion power during OLBNP. OLBNP power performed in isolation was compared with power during OLBNP plus arm flexion. Cerebral flow velocity oscillations at 0.05 Hz reduced and at 0.10 Hz eliminated functional hyperemia, while 0.03 Hz did not reach significance. In contrast, arm flexion reduced OLBNP-induced oscillatory power at all frequencies. The interactions between OLBNP-driven CBFv oscillations and arm flexion-driven CBFv oscillations are reciprocal. Thus induced cerebral blood flow oscillations suppress functional hyperemia, and functional hyperemia suppresses cerebral blood flow oscillations. We conclude that oscillatory cerebral blood flow produces a causal reduction of functional hyperemia. PMID- 26801311 TI - Maternal high-fat diet impairs cardiac function in offspring of diabetic pregnancy through metabolic stress and mitochondrial dysfunction. AB - Offspring of diabetic pregnancies are at risk of cardiovascular disease at birth and throughout life, purportedly through fuel-mediated influences on the developing heart. Preventative measures focus on glycemic control, but the contribution of additional offenders, including lipids, is not understood. Cellular bioenergetics can be influenced by both diabetes and hyperlipidemia and play a pivotal role in the pathophysiology of adult cardiovascular disease. This study investigated whether a maternal high-fat diet, independently or additively with diabetes, could impair fuel metabolism, mitochondrial function, and cardiac physiology in the developing offspring's heart. Sprague-Dawley rats fed a control or high-fat diet were administered placebo or streptozotocin to induce diabetes during pregnancy and then delivered offspring from four groups: control, diabetes exposed, diet exposed, and combination exposed. Cardiac function, cellular bioenergetics (mitochondrial stress test, glycolytic stress test, and palmitate oxidation assay), lipid peroxidation, mitochondrial histology, and copy number were determined. Diabetes-exposed offspring had impaired glycolytic and respiratory capacity and a reduced proton leak. High-fat diet-exposed offspring had increased mitochondrial copy number, increased lipid peroxidation, and evidence of mitochondrial dysfunction. Combination-exposed pups were most severely affected and demonstrated cardiac lipid droplet accumulation and diastolic/systolic cardiac dysfunction that mimics that of adult diabetic cardiomyopathy. This study is the first to demonstrate that a maternal high-fat diet impairs cardiac function in offspring of diabetic pregnancies through metabolic stress and serves as a critical step in understanding the role of cellular bioenergetics in developmentally programmed cardiac disease. PMID- 26801313 TI - Cardiac structure and function in adolescent Sherpa; effect of habitual altitude and developmental stage. AB - The purpose of this study was to examine ventricular structure and function in Sherpa adolescents to determine whether age-specific differences in oxygen saturation (SpO2 ) and pulmonary artery systolic pressure (PASP) influence cardiac adaptation to chronic hypoxia early in life. Two-dimensional, Doppler, and speckle-tracking echocardiography were performed on adolescent (9-16 yr) highland Sherpa (HLS; 3,840 m; n = 26) and compared with age-matched lowland Sherpa (LLS; 1,400 m; n = 10) and lowland Caucasian controls (LLC; sea level; n = 30). The HLS were subdivided into pre- and postadolescence; SpO2 was also recorded. Only HLS exhibited a smaller relative left ventricular (LV) end diastolic volume; however, both HLS and LLS demonstrated a lower peak LV untwisting velocity compared with LLC (92 +/- 26 and 100 +/- 45 vs. 130 +/- 43 degrees /s, P < 0.05). Although SpO2 was similar between groups, PASP was higher in post- vs. preadolescent HLS (30 +/- 5 vs. 25 +/- 5 mmHg, P < 0.05), which negatively correlated with right ventricular strain rate (r = 0.50, P < 0.01). Much like their adult counterparts, HLS and LLS adolescents exhibit slower LV diastolic relaxation, despite residing at different altitudes. These findings suggest fundamental differences exist in the diastolic function of Sherpa that are present at an early age and may be retained after migration to lower altitudes. The higher PASP in postadolescent Sherpa is in contrast to previous reports of lowland children at high altitude and, unlike that in lowlanders, was not explained by differences in SpO2 ; thus different regulatory mechanisms seem to exist between these two distinct populations. PMID- 26801312 TI - Ascorbic acid improves brachial artery vasodilation during progressive handgrip exercise in the elderly through a nitric oxide-mediated mechanism. AB - The proposed mechanistic link between the age-related attenuation in vascular function and free radicals is an attractive hypothesis; however, direct evidence of free radical attenuation and a concomitant improvement in vascular function in the elderly is lacking. Therefore, this study sought to test the hypothesis that ascorbic acid (AA), administered intra-arterially during progressive handgrip exercise, improves brachial artery (BA) vasodilation in a nitric oxide (NO) dependent manner, by mitigating free radical production. BA vasodilation (Doppler ultrasound) and free radical outflow [electron paramagnetic resonance (EPR) spectroscopy] were measured in seven healthy older adults (69 +/- 2 yr) during handgrip exercise at 3, 6, 9, and 12 kg (~13-52% of maximal voluntary contraction) during the control condition and nitric oxide synthase (NOS) inhibition via N(G)-monomethyl-L-arginine (L-NMMA), AA, and coinfusion of l-NMMA + AA. Baseline BA diameter was not altered by any of the treatments, while L-NMMA and L-NMMA + AA diminished baseline BA blood flow and shear rate. AA improved BA dilation compared with control at 9 kg (control: 6.5 +/- 2.2%, AA: 10.9 +/- 2.5%, P = 0.01) and 12 kg (control: 9.5 +/- 2.7%, AA: 15.9 +/- 3.7%, P < 0.01). NOS inhibition blunted BA vasodilation compared with control and when combined with AA eliminated the AA-induced improvement in BA vasodilation. Free radical outflow increased with exercise intensity but, interestingly, was not attenuated by AA. Collectively, these results indicate that AA improves BA vasodilation in the elderly during handgrip exercise through an NO-dependent mechanism; however, this improvement appears not to be the direct consequence of attenuated free radical outflow from the forearm. PMID- 26801314 TI - Bombesin-like receptor 3 regulates blood pressure and heart rate via a central sympathetic mechanism. AB - Bombesin-like receptor 3 (BRS-3) is an orphan G protein-coupled receptor that regulates energy expenditure, food intake, and body weight. We examined the effects of BRS-3 deletion and activation on blood pressure and heart rate. In free-living, telemetered Brs3 null mice the resting heart rate was 10% lower than wild-type controls, while the resting mean arterial pressure was unchanged. During physical activity, the heart rate and blood pressure increased more in Brs3 null mice, reaching a similar heart rate and higher mean arterial pressure than control mice. When sympathetic input was blocked with propranolol, the heart rate of Brs3 null mice was unchanged, while the heart rate in control mice was reduced to the level of the null mice. The intrinsic heart rate, measured after both sympathetic and parasympathetic blockade, was similar in Brs3 null and control mice. Intravenous infusion of the BRS-3 agonist MK-5046 increased mean arterial pressure and heart rate in wild-type but not in Brs3 null mice, and this increase was blocked by pretreatment with clonidine, a sympatholytic, centrally acting alpha2-adrenergic agonist. In anesthetized mice, hypothalamic infusion of MK-5046 also increased both mean arterial pressure and heart rate. Taken together, these data demonstrate that BRS-3 contributes to resting cardiac sympathetic tone, but is not required for activity-induced increases in heart rate and blood pressure. The data suggest that BRS-3 activation increases heart rate and blood pressure via a central sympathetic mechanism. PMID- 26801315 TI - Changes in Pain Processing in the Spinal Cord and Brainstem after Spinal Cord Injury Characterized by Functional Magnetic Resonance Imaging. AB - Traumatic spinal cord injury (SCI) has a number of devastating consequences, including high prevalence of chronic pain and altered pain sensitivity. The causes of altered pain states vary depending on the injury and are difficult to diagnose and treat. A better understanding of pain mechanisms after SCI is expected to lead to better diagnostic capabilities and improved treatments. We therefore applied functional magnetic resonance imaging (fMRI) of the brainstem and spinal cord in a group of participants with previous traumatic SCI to characterize changes in pain processing as a result of their injuries. The same thermal stimulus was applied to the medial palm (C8 dermatome) as a series of repeated brief noxious thermal pulses in a group of 16 participants with a cervical (n = 14) and upper thoracic (n = 2) injuries. Functional MRI of the brainstem and spinal cord was used to determine the neuronal activity evoked by the noxious stimulation, and connectivity between regions was characterized with structural equation modeling (SEM). The results show that pain ratings, the location and magnitude of blood oxygenation-level dependent fMRI results, and connectivity assessed with SEM varied widely across participants. However, the results varied in relation to the perceived pain and the level/severity of injuries, particularly in terms of hypothalamus connectivity with other regions, and descending modulation via the periaqueductal gray matter-rostral ventromedial medulla-cord pathway. The results, therefore, appear to provide sensitive indicators of each individual's pain response, and information about the mechanisms of altered pain sensitivity. The ability to characterize changes in pain processing in individuals with SCI represents a significant technological advance. PMID- 26801316 TI - Histology of Type 1 Diabetes Pancreas. AB - The islets of Langerhans play a critical role in glucose homeostasis. Islets are predominantly composed of insulin-secreting beta cells and glucagon-secreting alpha cells. In type 1 diabetes, the beta cells are destroyed by autoimmune destruction of insulin producing beta cells resulting in hyperglycemia. This is a gradual process, taking from several months to decades. Much of the beta cell destruction takes place during a silent, asymptomatic phase. Type 1 diabetes becomes clinically evident upon destruction of approximately 70-80 % of beta cell mass. Studying the decline in beta cell mass and the cells which are responsible for their demise is difficult as pancreatic biopsies are not feasible in patients with type 1 diabetes. The relative size of islets and their dispersed location throughout the pancreas means in vivo imaging of human islets is currently not manageable. At present, there are no validated biomarkers which accurately track the decline in beta cell mass in individuals who are at risk of developing, or have already developed, type 1 diabetes. Therefore, studies of pancreatic tissue retrieved at autopsy from donors with type 1 diabetes, or donors with high risk markers of type 1 diabetes such as circulating islet-associated autoantibodies, is currently the best method for studying beta cells and the associated inflammatory milieu in situ. In recent years, concerted efforts have been made to source such tissues for histological studies, enabling great insights to be made into the relationship between islets and the inflammatory insult to which they are subjected. This article describes in detail, a robust immunohistochemical method which can be utilized to study both recent, and archival human pancreatic tissue, in order to examine islet endocrine cells and the surrounding immune cells. PMID- 26801317 TI - Prediction of Human Glomerular Filtration Rate from Preterm Neonates to Adults: Evaluation of Predictive Performance of Several Empirical Models. AB - The objective of this study was to evaluate the predictive performance of several allometric empirical models (body weight dependent, age dependent, fixed exponent 0.75, a data-dependent single exponent, and maturation models) to predict glomerular filtration rate (GFR) in preterm and term neonates, infants, children, and adults without any renal disease. In this analysis, the models were developed from GFR data obtained from inulin clearance (preterm neonates to adults; n = 93) and the predictive performance of these models were evaluated in 335 subjects (preterm neonates to adults). The primary end point was the prediction of GFR from the empirical allometric models and the comparison of the predicted GFR with measured GFR. A prediction error within +/-30% was considered acceptable. Overall, the predictive performance of the four models (BDE, ADE, and two maturation models) for the prediction of mean GFR was good across all age groups but the prediction of GFR in individual healthy subjects especially in neonates and infants was erratic and may be clinically unacceptable. PMID- 26801318 TI - Plastic and evolutionary responses to heat stress in a temperate dung fly: negative correlation between basal and induced heat tolerance? AB - Extreme weather events such as heat waves are becoming more frequent and intense. Populations can cope with elevated heat stress by evolving higher basal heat tolerance (evolutionary response) and/or stronger induced heat tolerance (plastic response). However, there is ongoing debate about whether basal and induced heat tolerance are negatively correlated and whether adaptive potential in heat tolerance is sufficient under ongoing climate warming. To evaluate the evolutionary potential of basal and induced heat tolerance, we performed experimental evolution on a temperate source population of the dung fly Sepsis punctum. Offspring of flies adapted to three thermal selection regimes (Hot, Cold and Reference) were subjected to acute heat stress after having been exposed to either a hot-acclimation or non-acclimation pretreatment. As different traits may respond differently to temperature stress, several physiological and life history traits were assessed. Condition dependence of the response was evaluated by exposing juveniles to different levels of developmental (food restriction/rearing density) stress. Heat knockdown times were highest, whereas acclimation effects were lowest in the Hot selection regime, indicating a negative association between basal and induced heat tolerance. However, survival, adult longevity, fecundity and fertility did not show such a pattern. Acclimation had positive effects in heat-shocked flies, but in the absence of heat stress hot-acclimated flies had reduced life spans relative to non-acclimated ones, thereby revealing a potential cost of acclimation. Moreover, body size positively affected heat tolerance and unstressed individuals were less prone to heat stress than stressed flies, offering support for energetic costs associated with heat tolerance. Overall, our results indicate that heat tolerance of temperate insects can evolve under rising temperatures, but this response could be limited by a negative relationship between basal and induced thermotolerance, and may involve some but not other fitness-related traits. PMID- 26801319 TI - Comparison of novel and conventional methods of trapping ixodid ticks in the southeastern U.S.A. AB - Tick-borne disease surveillance and research rely on resource-effective methods for tick collection. This study compared the respective performances of several trapping methods in a mixed grassland-forest habitat in western Tennessee. To test for temporal differences in effectiveness, sites were sampled monthly (April August 2013) using dry ice, dragging, flagging, sweep netting, carbon dioxide (CO2 ) dragging and CO2 flagging methods. To evaluate the effect of habitat on method effectiveness, four methods (dragging, CO2 dragging, CO2 flagging and dry ice) were compared in four habitat types (bottomland deciduous, upland deciduous, coniferous and grassland) in June 2014. In the temporal comparison, ticks were found to be most abundant in April and May, and there was a significant sampling period and method interaction, such that method effectiveness varied across sampling period. Sweep netting was significantly less effective than the other methods. In the habitat comparison, dry ice trap collections represented the most effective method in upland deciduous and coniferous habitats. Flagging using CO2 was significantly less effective than CO2 dragging and dragging in bottomland deciduous habitats. The success of the various collection methods did not differ significantly within grassland habitats. Overall, dry ice trapping and dragging were the most effective methods for tick collection across time and habitat. PMID- 26801320 TI - Inhibition of heme oxygenase-1 enhances the chemosensitivity of laryngeal squamous cell cancer Hep-2 cells to cisplatin. AB - It has been previously reported that cisplatin is a well-known anticancer drug being used against a wide range of malignancies including head and neck, ovarian and non-small cell lung carcinoma, and demonstrated its anticancer activity by reacting with DNA or changing cell structure, immune response, reactive oxygen species level (ROS). In this research we proved that cisplatin induced cell injuries and heme oxygenase-1 (HO-1) expression in laryngeal squamous cell cancer Hep-2 cells through ROS generation. The induction of HO-1 clearly protected Hep-2 cells from cisplatin-induced cell death and ROS reaction, and the inhibitor of HO 1 enhanced the cell death and ROS generation induced by cisplatin. Furthermore, the HO-1 expression induced by cisplatin was strongly inhibited by the knockdown of nuclear factor-erythroid-2-related factor-2 (Nrf-2), and the oxidative damages induced by cisplatin were significantly enhanced. Therefore, it may be concluded that the inhibition of HO-1 or the knockdown of Nrf-2 significantly enhanced cisplatin's anticancer effects on Hep-2 cells. In clinic, with the overexpression of HO-1 in laryngeal squamous cancer tissues, the combination of cisplatin with the inhibitor of HO-1 or Nrf-2 siRNA may act as a new method to the treatment of laryngeal squamous cancer. PMID- 26801321 TI - Caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress. AB - It is well recognized that mandibular growth, which is caused by a variety of functional appliances, is considered to be the result of both neuromuscular and skeletal adaptations. Accumulating evidence has demonstrated that apoptosis plays an important role in the adaptation of skeletal muscle function. However, the underlying mechanism of apoptosis that is induced by stretch continues to be incompletely understood. Endoplasmic reticulum stress (ERS), a newly defined signaling pathway, initiates apoptosis. This study seeks to determine if caspase 12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress in myoblast and its underlying mechanism. Apoptosis was assessed by Hochest staining, DAPI staining and annexin V binding and PI staining. ER chaperones, such as GRP78, CHOP and caspase-12, were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Furthermore, caspase-12 inhibitor was used to value the mechanism of the caspase-12 pathway. Apoptosis of myoblast, which is subjected to cyclic stretch, was observed in a time-dependent manner. We found that GRP78 mRNA and protein were significantly increased and CHOP and caspase-12 were activated in myoblast that was exposed to cyclic stretch. Caspase-12 inhibition reduced stretch-induced apoptosis, and caspase-12 activated caspase-3 to induce apoptosis. We concluded that caspase-12 played an important role in stretch-induced apoptosis that is associated by endoplasmic reticulum stress by activating caspase-3. PMID- 26801322 TI - [Visual prostheses]. AB - Sensory neuroprostheses for restoration of vision are a technical approach for treatment of previously untreatable blindness. These systems consist of a technical sensor such as a camera and an implanted multi-electrode array within the visual system. The image information from the sensor is processed with specially designed integrated circuits in such a way that the stimulation pulses can be determined and presented to the implanted multi-electrode matrix. Energy supply and the transfer of the stimulus pulse information is realized either via direct cable connections within the site of the implant or by telemetric inductive links. Currently, two retinal implant systems are approved in the European Union (EU) to be used in blind patients with retinitis pigmentosa. With both systems basic visual functions can be restored. The complication rate is relatively low given the complexity of the surgical procedure. Other systems are still under development but approval studies by several manufacturers and consortia are already in preparation. PMID- 26801323 TI - [Analysis of cardiovascular diseases after the upload phase with intravitreal ranibizumab and bevacizumab in patients with exudative age-related macular degeneration]. AB - BACKGROUND: The intravitreal administration of vascular endothelial growth factor (VEGF) inhibitors is the gold standard in the treatment of exudative age-related macular degeneration (AMD) but the possible risks of systemic, particularly cardiovascular side effects are still discussed. PATIENTS AND METHODS: We prospectively followed 111 patients at the University Hospital in Gottingen with exudative AMD and intravitreal ocular treatment with bevacizumab and ranibizumab during the upload phase of 3 months using a questionnaire for documentation of possible cardiovascular events. RESULTS: In 5 out of 111 patients angina pectoris was observed and in 6 patients the antihypertensive medication had to be increased. No differences were found between bevacizumab and ranibizumab. A patient with pre-existing cardiovascular diseases suffered a stroke in the upload phase but no thromboembolic events were observed in the other patients. CONCLUSION: In this small but prospective clinical study no increased risk for cardiovascular events during the upload phase of the VEGF inhibitors ranibizumab and bevacizumab could be detected when taking the age and pre-existing cardiovascular diseases into consideration. PMID- 26801324 TI - [Mucinous sweat gland carcinoma of the eyelid]. AB - A 52-year-old patient presented with a painless nodular tumor of the upper left eyelid, which was first noticed 6 months prior to the initial presentation. The histopathological and immunohistochemical examination of the excised tumor revealed a mucinous sweat gland carcinoma. This very rare neoplasm (1/150,000 skin lesions) is located within the ocular adnexa in 40 % of cases. If completely excised the prognosis is usually good; however, due to the histological similarity to metastases of an adenocarcinoma, a hitherto unknown primary tumor at another site should be excluded. PMID- 26801325 TI - [Endocrine ophthalmopathy. A visible psychophysical complaint]. AB - BACKGROUND: Endocrine orbitopathy (Graves' disease) is an autoimmune disease based on a genetic predisposition. Patients with a visible exophthalmos were examined and treated in the department of ophthalmology. OBJECTIVES: Is there an association between the formation of exophthalmos and life situations and events? MATERIAL AND METHODS: A total of 64 patients with exophthalmos due to Graves' disease were asked to complete a questionnaire to evaluate psychosocial morbidity, the quality of life, social background and stressful life events. RESULTS: The results revealed that 60% of the participants had experienced stressful life events (e.g. workplace, parents, children and partner), mainly bereavement in the months before onset of the disease. The psychosocial background revealed that they were predominantly from a low social status and lived in unsatisfactory employment, partner and environmental conditions. CONCLUSION: Graves' disease is an autoimmune disease and is substantially triggered by psychosocial factors. The necessary interdisciplinary therapy should include medical psychotherapy. PMID- 26801326 TI - Establishing an institutional therapeutic apheresis registry. AB - Apheresis was first performed as a therapeutic procedure in the 1950s. The first national therapeutic apheresis (TA) registry was established in Canada in 1981 and other national registries followed, including two attempts at establishing an international TA registry. There is no national registry in the United States. Our large, academic, tertiary hospital has a very active TA service. We created a TA database to track all procedures performed by the apheresis service by transferring data from paper appointment logs and the electronic medical records into a Microsoft Access database. Retrospective data from each TA procedure performed at UAB from January 1, 2003 through December 31, 2012 were entered, including the type of procedure, indication, date, and patient demographics. Microsoft Excel was used for data analysis. During the 10-year period, our TA service treated 1,060 patients and performed 11,718 procedures. Of these patients, 70% received therapeutic plasma exchange (TPE), 21% received extracorporeal photopheresis (ECP), 4.5% received red cell exchange (RCE), 4.2% received leukocytapheresis, and 0.6% underwent platelet depletion. Among the procedures, 54% were TPEs, 44% were ECPs, 1.3% were RCEs, 0.5% were leukocytaphereses, and 0.1% were platelet depletions. According to the current literature, national and international TA use is underreported. We believe that the UAB TA registry provides useful information about TA practices in our region and can serve as a model for other institutions. Furthermore, data from multiple institutional registries can be used for clinical research to increase the available evidence for the role of TA in various conditions. J. Clin. Apheresis 31:516-522, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26801327 TI - Targeting of radiolabeled J591 antibody to PSMA-expressing tumors: optimization of imaging and therapy based on non-linear compartmental modeling. AB - BACKGROUND: We applied a non-linear immunokinetic model to quantitatively compare absolute antibody uptake and turnover in subcutaneous LNCaP human prostate cancer (PCa) xenografts of two radiolabeled forms of the humanized anti-prostate specific membrane antigen (PSMA) monoclonal antibody J591 ((124)I-J591 and (89)Zr J591). Using the model, we examined the impact of dose on the tumor and plasma positron emission tomography (PET)-derived time-activity curves. We also sought to predict the optimal targeting index (ratio of integrated-tumor-to-integrated plasma activity concentrations) for radioimmunotherapy. METHODS: The equilibrium rates of antibody internalization and turnover in the tumors were derived from PET images up to 96 h post-injection using compartmental modeling with a non linear transfer rate. In addition, we serially imaged groups of LNCaP tumor bearing mice injected with (89)Zr-J591 antibody doses ranging from antigen subsaturating to saturating to examine the suitability of using a non-linear approach and derived the time-integrated concentration (in MUM?hours) of administered tracer in tumor as a function of the administered dose of antibody. RESULTS: The comparison of (124)I-J591 and (89)Zr-J591 yielded similar model derived values of the total antigen concentration and internalization rate. The association equilibrium constant (k a) was twofold higher for (124)I, but there was a ~tenfold greater tumoral efflux rate of (124)I from tumor compared to that of (89)Zr. Plots of surface-bound and internalized radiotracers indicate similar behavior up to 24 h p.i. for both (124)I-J591 and (89)Zr-J591, with the effect of differential clearance rates becoming apparent after about 35 h p.i. Estimates of J591/PSMA complex turnover were 3.9-90.5 * 10(12) (for doses from 60 to 240 MUg) molecules per hour per gram of tumor (20 % of receptors internalized per hour). CONCLUSIONS: Using quantitative compartmental model methods, surface binding and internalization rates were shown to be similar for both (124)I-J591 and (89)Zr J591 forms, as expected. The large difference in clearance rates of the radioactivity from the tumor is likely due to differential trapping of residualizing zirconium versus non-residualizing iodine. Our non-linear model was found to be superior to a conventional linear model. This finding and the calculated activity persistence time in tumor have important implications for radioimmunotherapy and other antibody-based therapies in patients. PMID- 26801328 TI - Evaluating the Clinical Applicability of the European Staging System for Perihilar Cholangiocarcinoma. AB - BACKGROUND: In 2011, a new European Staging System (ESS) for perihilar cholangiocarcinoma (PHC) was proposed with the expressed purpose of comparing treatment and outcomes data between institutions. The goal of this study was to evaluate the feasibility of ESS data capture. STUDY DESIGN: Forty-seven consecutive patients who underwent surgical resection for PHC between 1999 and 2013 were studied. Demographic variables, components of various staging systems (including the ESS), preoperative and perioperative details, pathology, and outcomes were recorded. RESULTS: The mean patient age was 63.2 and 62% were male. Preoperative imaging included high-resolution CT in all patients, MRI in 34%, and PET in 11%. R0 resection was accomplished in 80% of patients. Four patients (8.5%) and 18 patients (38.3%), respectively, received neoadjuvant or adjuvant therapy. During a mean follow-up of 36 months, recurrence rate was 51.3% and 2- and 5-year survival rates were 69.4 and 33.3%, respectively. Analysis of data capture found that tumor (T) classification was indeterminable in 7/47 patients (14.9%). For two patients, the form (F) designation had insufficient data. The extent of vascular involvement (PV/HA) was different compared to preoperative imaging in nine patients (19.1%). The liver remnant volume (V) was calculated in only 18 patients (38.3%). The liver disease (D) variable did not account for four patients with inflammation/cirrhosis. In total, only 15 patients (31.9%) had all required elements to complete the ESS. CONCLUSIONS: Without templated radiology, surgery, and pathology reports, the ESS cannot be applied to current clinical/research practice. Although resection continues to provide significant survival benefit to patients with perihilar cholangiocarcinoma, lack of an accurate prognostic tool for resectability and outcomes continues to be a major impediment to progress in the field. PMID- 26801329 TI - Functional characterization of a Glycine soja Ca(2+)ATPase in salt-alkaline stress responses. AB - It is widely accepted that Ca(2+)ATPase family proteins play important roles in plant environmental stress responses. However, up to now, most researches are limited in the reference plants Arabidopsis and rice. The function of Ca(2+)ATPases from non-reference plants was rarely reported, especially its regulatory role in carbonate alkaline stress responses. Hence, in this study, we identified the P-type II Ca(2+)ATPase family genes in soybean genome, determined their chromosomal location and gene architecture, and analyzed their amino acid sequence and evolutionary relationship. Based on above results, we pointed out the existence of gene duplication for soybean Ca(2+)ATPases. Then, we investigated the expression profiles of the ACA subfamily genes in wild soybean (Glycine soja) under carbonate alkaline stress, and functionally characterized one representative gene GsACA1 by using transgenic alfalfa. Our results suggested that GsACA1 overexpression in alfalfa obviously increased plant tolerance to both carbonate alkaline and neutral salt stresses, as evidenced by lower levels of membrane permeability and MDA content, but higher levels of SOD activity, proline concentration and chlorophyll content under stress conditions. Taken together, for the first time, we reported a P-type II Ca(2+)ATPase from wild soybean, GsACA1, which could positively regulate plant tolerance to both carbonate alkaline and neutral salt stresses. PMID- 26801332 TI - Body mass index and response to tocilizumab in rheumatoid arthritis: a real life study. AB - Several studies have suggested that obesity could have a negative effect on response to anti-tumor necrosis factor alpha (anti-TNFalpha) in rheumatoid arthritis (RA). Little is known about the impact of body mass index (BMI) on other biologic agents. We aimed to evaluate the effect of BMI on response to tocilizumab (TCZ) in RA. RA patients treated with TCZ were included in this multicenter retrospective study. BMI was calculated at the initiation of treatment. After 6 months of treatment, change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate and C-reactive protein level, and tender and swollen joints were analyzed. The primary endpoint was decrease in DAS28 >= 1.2. Secondary outcomes were good response and remission by EULAR criteria. At baseline, among 115 RA patients included, the median (interquartile range) BMI was 25.4 (22.0-28.8) kg/m(2). The number of patients with normal weight, overweight, and obesity was 53 (46 %), 37 (32 %), and 25 (22 %), respectively. Baseline characteristics did not differ between the three subgroups of BMI. The median BMI did not differ between responders and non-responders for DAS28 decrease >=1.2 (25.7 [22.1-29.9] vs 24.9 [22.0-27.1], P = 0.38), EULAR good response (25.9 [22.8-30.0] vs 25.4 [22.0-28.4], P = 0.61), and remission (25.1 [22.5-28.6] vs 25.4 [22.0-28.9], P = 0.76). BMI did not affect the response to TCZ in RA. If confirmed, these results could be helpful for the selection of a biologic agent in obese RA patients. PMID- 26801333 TI - gamma-Secretase inhibitor reverts the Notch signaling attenuation of osteogenic differentiation in aged bone marrow mesenchymal stem cells. AB - The age-related changes in cell viability and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) play pivotal roles in the fracture healing process, especially in geriatric individuals. This study was designed to explore the age-related changes in murine BMSCs and the regulation of osteogenic differentiation in aged BMSCs in vitro. Notch signaling pathway took part in the regulation of osteogensis, while the relationship between Notch and the osteogenic differentiation in aged BMSCs has not been reported yet. BMSCs harvested from the bone marrow of young, adult, and aged C57BL/6 mice were cultured in osteogenic and adipogenic differentiation media. Histochemical staining results indicated that the osteogenic ability of BMSCs gradually decreased with aging, whereas the adipogenic ability increased. Cell activity assays showed that the proliferative and migrated capacity did not decline with aging significantly. According to real-time PCR and Western blotting results, the aged cells exhibited higher Notch signaling expression level than the younger ones did. After the aged BMSCs being treated with gamma-secretase inhibitor, however, Notch activity was changed and the aging-imparied osteogenic ability reverted to a normal level. This study demonstrated that the decreased bone formation capacity in aged BMSCs had relationship with the transdifferentiation between osteogenesis and adipogenesis, which would be regulated by Notch signaling pathway and the attenuated osteogenesis in aged BMSCs could be promoted when the inhibition of Notch pathway. PMID- 26801330 TI - RNA-seq transcriptional profiling of Herbaspirillum seropedicae colonizing wheat (Triticum aestivum) roots. AB - Herbaspirillum seropedicae is a diazotrophic and endophytic bacterium that associates with economically important grasses promoting plant growth and increasing productivity. To identify genes related to bacterial ability to colonize plants, wheat seedlings growing hydroponically in Hoagland's medium were inoculated with H. seropedicae and incubated for 3 days. Total mRNA from the bacteria present in the root surface and in the plant medium were purified, depleted from rRNA and used for RNA-seq profiling. RT-qPCR analyses were conducted to confirm regulation of selected genes. Comparison of RNA profile of root attached and planktonic bacteria revealed extensive metabolic adaptations to the epiphytic life style. These adaptations include expression of specific adhesins and cell wall re-modeling to attach to the root. Additionally, the metabolism was adapted to the microxic environment and nitrogen-fixation genes were expressed. Polyhydroxybutyrate (PHB) synthesis was activated, and PHB granules were stored as observed by microscopy. Genes related to plant growth promotion, such as auxin production were expressed. Many ABC transporter genes were regulated in the bacteria attached to the roots. The results provide new insights into the adaptation of H. seropedicae to the interaction with the plant. PMID- 26801334 TI - Ascochyta blight disease of pea (Pisum sativum L.): defence-related candidate genes associated with QTL regions and identification of epistatic QTL. AB - KEY MESSAGE: Advances have been made in our understanding of Ascochyta blight resistance genetics through mapping candidate genes associated with QTL regions and demonstrating the importance of epistatic interactions in determining resistance. Ascochyta blight disease of pea (Pisum sativum L.) is economically significant with worldwide distribution. The causal pathogens are Didymella pinodes, Phoma medicaginis var pinodella and, in South Australia, P. koolunga. This study aimed to identify candidate genes that map to quantitative trait loci (QTL) for Ascochyta blight field disease resistance and to explore the role of epistatic interactions. Candidate genes associated with QTL were identified beginning with 101 defence-related genes from the published literature. Synteny between pea and Medicago truncatula was used to narrow down the candidates for mapping. Fourteen pea candidate sequences were mapped in two QTL mapping populations, A26 * Rovar and A88 * Rovar. QTL peaks, or the intervals containing QTL peaks, for the Asc2.1, Asc4.2, Asc4.3 and Asc7.1 QTL were defined by four of these candidate genes, while another three candidate genes occurred within 1.0 LOD confidence intervals. Epistasis involving QTL * background marker and background marker * background marker interactions contributed to the disease response phenotypes observed in the two mapping populations. For each population, five pairwise interactions exceeded the 5% false discovery rate threshold. Two candidate genes were involved in significant pairwise interactions. Markers in three genomic regions were involved in two or more epistatic interactions. Therefore, this study has identified pea defence-related sequences that are candidates for resistance determination, and that may be useful for marker assisted selection. The demonstration of epistasis informs breeders that the architecture of this complex quantitative resistance includes epistatic interactions with non-additive effects. PMID- 26801335 TI - A novel er1 allele and the development and validation of its functional marker for breeding pea (Pisum sativum L.) resistance to powdery mildew. AB - KEY MESSAGE: A novel er1 allele, er1 -7, conferring pea powdery mildew resistance was characterized by a 10-bp deletion in PsMLO1 cDNA, and its functional marker was developed and validated in pea germplasms. Pea powdery mildew caused by Erysiphe pisi DC is a major disease worldwide. Pea cultivar 'DDR-11' is an elite germplasm resistant to E. pisi. To identify the gene conferring resistance in DDR 11, the susceptible Bawan 6 and resistant DDR-11 cultivars were crossed to produce F1, F2, and F(2:3) populations. The phenotypic segregation patterns in the F2 and F(2:3) populations fit the 3:1 (susceptible:resistant) and 1:2:1 (susceptible homozygotes:heterozygotes:resistant homozygotes) ratios, respectively, indicating that resistance was controlled by a single recessive gene. Analysis of er1-linked markers in the F2 population suggested that the recessive resistance gene in DDR-11 was an er1 allele, which was mapped between markers ScOPE16-1600 and c5DNAmet. To further characterize er1 allele, the cDNA sequences of PsMLO1 from the parents were obtained and a novel er1 allele in DDR 11 was identified and designated as er1-7, which has a 10-bp deletion in position 111-120. The er1-7 allele caused a frame-shift mutation, resulting in a premature termination of translation of PsMLO1 protein. A co-dominant functional marker specific for er1-7 was developed, InDel111-120, which co-segregated with E. pisi resistance in the mapping population. The marker was able to distinguish between pea germplasms with and without the er1-7. Of 161 pea germplasms tested by InDel111-120, seven were detected containing resistance allele er1-7, which was verified by sequencing their PsMLO1 cDNA. Here, a novel er1 allele was characterized and its an ideal functional marker was validated, providing valuable genetic information and a powerful tool for breeding pea resistance to powdery mildew. PMID- 26801336 TI - The Baby-Friendly Hospital Initiative as an Intervention to Improve Breastfeeding Rates: A Review of the Literature. AB - INTRODUCTION: The Baby-Friendly Hospital Initiative (BFHI) is considered to be an evidence-based program that improves breastfeeding outcomes, but primary research on the topic has been limited. The purpose of this review was to evaluate the literature and synthesize findings to determine the effectiveness of the BFHI as an intervention to improve breastfeeding initiation, duration, and exclusivity. METHODS: A review of literature published from 1991 to October 2014 using MEDLINE, CINAHL, PsycINFO, and Web of Knowledge with the search term "Baby Friendly Hospital Initiative." The 724 titles initially identified were reviewed using these inclusion criteria: English language, primary research, and available electronically or via interlibrary loan. Studies were excluded if they explicitly stated that they had omitted specific portions of the BFHI or did not fully implement the intervention; considered breastfeeding rather than the BFHI as an intervention; used the BFHI to improve neonatal intensive care unit outcomes specifically; or measured outcomes other than breastfeeding initiation, duration, or exclusivity. This yielded 25 studies for review. RESULTS: There are more studies that support the BFHI as an intervention to increase breastfeeding than there are studies that demonstrate no effect of the intervention. However, design weaknesses, settings outside the United States, and disparate methods impede the ability to reach firm conclusions regarding the effectiveness of the BFHI in improving breastfeeding initiation, duration, and exclusivity rates in the United States. DISCUSSION: Many of the studies regarding the effectiveness of the BFHI have been hampered by weak designs or methodologic limitations. Research conducted in the United States and employing experimental designs would help to more conclusively determine the effectiveness of the BFHI as an intervention to improve breastfeeding rates. PMID- 26801337 TI - Using perceptions as evidence to improve conservation and environmental management. AB - The conservation community is increasingly focusing on the monitoring and evaluation of management, governance, ecological, and social considerations as part of a broader move toward adaptive management and evidence-based conservation. Evidence is any information that can be used to come to a conclusion and support a judgment or, in this case, to make decisions that will improve conservation policies, actions, and outcomes. Perceptions are one type of information that is often dismissed as anecdotal by those arguing for evidence based conservation. In this paper, I clarify the contributions of research on perceptions of conservation to improving adaptive and evidence-based conservation. Studies of the perceptions of local people can provide important insights into observations, understandings and interpretations of the social impacts, and ecological outcomes of conservation; the legitimacy of conservation governance; and the social acceptability of environmental management. Perceptions of these factors contribute to positive or negative local evaluations of conservation initiatives. It is positive perceptions, not just objective scientific evidence of effectiveness, that ultimately ensure the support of local constituents thus enabling the long-term success of conservation. Research on perceptions can inform courses of action to improve conservation and governance at scales ranging from individual initiatives to national and international policies. Better incorporation of evidence from across the social and natural sciences and integration of a plurality of methods into monitoring and evaluation will provide a more complete picture on which to base conservation decisions and environmental management. PMID- 26801338 TI - The interrelations between spiritual well-being, pain interference and depressive symptoms in patients with multiple sclerosis. AB - Depressive symptoms are common in individuals with multiple sclerosis (MS), and are frequently exacerbated by pain; however, spiritual well-being may allow persons with MS to more effectively cope with pain-related deficits in physical and role functioning. We explored the associations between spiritual well-being, pain interference and depressive symptoms, assessing each as a potential mediator, in eighty-one patients being treated for MS, who completed self-report measures: Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale, Pain Effects Scale, and Center for Epidemiologic Studies Depression Scale Revised. At the bivariate level, spiritual well-being and its subscale of meaning and peace were negatively associated with depression and pain interference. In mediation models, depression was not related to pain interference via spiritual well-being, or to spiritual well-being via pain interference. Pain interference was related to depression via spiritual well-being and meaning/peace, and to spiritual well-being and meaning/peace via depressive symptoms. Finally, spiritual well-being and meaning/peace were related to depression via pain interference, and to pain interference via depressive symptoms. For patients with MS, a multi-faceted approach to treatment that includes pain reduction and promotion of spiritual well-being may be beneficial, although amelioration of depression remains a critical task. PMID- 26801339 TI - The role of social support in weight loss maintenance: results from the MedWeight study. AB - The role of social support in weight management is not fully understood, as more support has been linked to both favorable and unfavorable outcomes. We examined social support in relation to weight loss maintenance, comparing between maintainers and regainers of weight loss. The MedWeight study is a Greek registry of people who have intentionally lost >=10 % of their weight and are either maintaining this loss for over a year (maintainers), or have regained weight (regainers). Demographics and lifestyle habits questionnaires are completed online. Dietary assessment is carried out by two telephone 24 h recalls. Perceived social support was assessed by validated scales examining support from family and friends regarding healthy eating and exercise. 289 maintainers and 122 regainers participated. Regainers received more support compared to maintainers. However, maintainers reported receiving compliments and active participation, whereas regainers receiving verbal instructions and encouragements. Maintainers who received diet support displayed improved dietary intakes, such as lower energy intake; regainers' diet was unaffected by support. Positive, rather than instructive, support appears beneficial in weight loss maintenance. PMID- 26801340 TI - Measures of food intake in mantled howling monkeys. AB - Food intake (i.e., the amount of food consumed by an individual) is a crucial measure for studying feeding behavior, but its measurement requires high visibility of individuals and long recording sessions, which are often difficult to accomplish under field conditions. As a consequence, studies on the feeding behavior of primates typically do not estimate food intake directly, and focus rather on studying dietary patterns through indirect measures of food intake, such as time spent feeding, number of food bites and food intake rates. The aim of the present study was to determine the validity of these estimators of food intake in mantled howling monkeys (Alouatta palliata) by comparing the estimations with the direct measurement of food intake. We recorded 97 feeding episodes of two male and two female adults, during which we determined the number of ingested food units (i.e., number of leaves and number of fruits), the number of bites taken and time spent feeding. After weighing units of food similar to those consumed, we calculated food intake and mean intake rates per food type (ripe fruits, unripe fruits, mature leaves, and young leaves). The number of bites taken by mantled howling monkeys during feeding episodes was strongly related to food intake, and this relationship was not affected by the type of food ingested. In contrast, neither time spent feeding nor food ingestion rate were related to food intake. These results suggest that the number of bites could be used as a valid proxy to study food intake in this species, whereas the other two measures are likely to yield inaccurate estimates of food intake. PMID- 26801341 TI - A comparison of adult body size between captive and wild vervet monkeys (Chlorocebus aethiops sabaeus) on the island of St. Kitts. AB - Weight and 34 morphological measurements were obtained from 103 vervet monkeys living either in the wild or in captive colonies derived from the wild populations on the island of St. Kitts in the Eastern Caribbean. All measures were taken during the same week, eliminating bias that might result from changing seasonal environmental conditions. Vervets on St. Kitts are all descended from a small number of individuals brought to the island approximately 400 years ago from West Africa, thus eliminating bias that might result from subspecific size differences. We conducted a principal components analysis (PCA) and compared individual traits between captive and wild adult animals. Morphological measures such as body, arm, and leg length did not differ significantly between animals living in the wild and animals in captivity. Weight and measures indicating condition-including body mass index (BMI), chest, thigh, and upper arm girth were all higher for animals living in captivity. More consistent available food is probably the cause of differences in measures reflecting condition. PMID- 26801342 TI - Clinical use of ipilimumab for metastatic melanoma in Spain: towards a more consistent approach. AB - INTRODUCTION: Ipilimumab has been approved in patients with advanced melanoma by different regulatory bodies worldwide, but its use in clinical practice is not fully consistent among oncologists. We have surveyed a representative sample of Spanish medical oncologists on issues related to the use of ipilimumab. MATERIALS AND METHODS: The survey was based on the Delphi method, where experts respond anonymously to two rounds of a questionnaire. Questionnaire consisted of 42 statements divided among the following eight categories: Pathology and Diagnosis; Patterns of Response; Parameters affecting Treatment Selection; Patient Profile; Sequencing of Treatment; Definition of Long-Term Survivors; Quality of Life; Concept of Immuno-oncology. The experts were asked to rate each statement on a scale of 1-9, where 1 meant "completely disagree" and 9 meant "completely agree". RESULTS: Thirty-three oncologists responded to both rounds of the survey (62.3 % of total surveyed). On issues related to pathology and diagnosis, patterns of response, and immuno-oncology, the specialists reached a high level of consensus. There was also a high level of agreement, albeit without consensus on assessment of BRAF mutations before deciding on treatment with ipilimumab. However, there was a lower level of agreement on sequencing treatment with BRAF inhibitors and ipilimumab, on predictive factors, on the use of corticosteroids, and on patient quality of life. CONCLUSIONS: The disparity in many of these topics suggests that oncologists need more information on certain aspects of ipilimumab treatment. We need to define generally accepted algorithms of treatment, especially with regard to issues that were shown to be controversial or unclear. PMID- 26801343 TI - Clinical features and management of afferent limb syndrome after ileal pouch-anal anastomosis for ulcerative colitis. AB - PURPOSE: Afferent limb syndrome (ALS) is a type of small bowel obstruction (SBO) caused by obstruction of the afferent intestinal limb after ileal pouch-anal anastomosis (IPAA). The aim of this study was to reveal the clinical features and management of ALS. METHODS: Of 320 patients undergoing IPAA for ulcerative colitis, we analyzed data from patients presenting with SBO. RESULTS: Six of 19 patients with SBO were diagnosed with ALS. All patients with ALS presented with recurrent intermittent obstructive symptoms before admission, whereas 15 % of patients without ALS presented with these symptoms (P < 0.0005). Among the six patients with ALS, four patients required surgery, although they underwent transanal decompression for each episode of obstruction. The proportion of surgery was higher in the ALS group (P < 0.01). Acute angulation of the afferent limb was recognized in four cases and followed by fixation of the afferent limb. No further surgery was required in any patient following the last fixation. CONCLUSIONS: SBO after IPAA may be caused by acute angulation of the afferent limb of the ileal J-pouch. Most patients with ALS may eventually require fixation of the afferent limb due to acute angulation of the afferent limb. PMID- 26801345 TI - Participant views on consent in cancer genetics research: preparing for the precision medicine era. AB - The Precision Medicine Initiative (PMI) has created considerable discussions about research participant issues including re-consent and how and when to incorporate the patient experience into clinical trials. Within the changing landscape of genetic and genomic research, the preferences of participants are lacking yet are needed to inform policy. With the growing use of biobanks intended to support studies, including the national research cohort proposed under the PMI, understanding participant preferences, including re-consent, is a pressing concern. The Participant Issues Project (PIP) addresses this gap, and here we present data on participant attitudes regarding re-consent and broad consent in research studies. PIP study participants came from the Northwest Cancer Genetics Registry and included cancer patients, relatives, and controls. Thirty telephone interviews were conducted and analyzed using content and thematic analysis. Results indicate that in some scenarios, re-consent is needed. Most participants agreed that re-consent was necessary when the study direction changed significantly or a child participant became an adult, but not if the genetic variant changed. Most participants' willingness to participate in research would not be affected if the researcher or institution profited or if a broad consent form were used. Participants emphasized re-consent to provide information and control of the use of their data, now relevant for tailored treatment, while also prioritizing research as important. In the era of precision medicine, it is essential that policy makers consider participant preferences with regard to use of their materials and that participants understand genetic and genomic research and its harms and benefits as well as what broad consent entails, including privacy and re-identification risks. PMID- 26801344 TI - An increased number of PD-1+ and Tim-3+ CD8+ T cells is involved in immune evasion in gastric cancer. AB - PURPOSE: Co-signaling molecules play an important role in T cells. This study was designed to investigate PD-1 and Tim-3 expression on T cells and the relationships between PD-1 and Tim-3 expression and immune evasion in patients with gastric cancer. METHODS: Using multicolor flow cytometry, we analyzed PD-1 and Tim-3 expression on CD8+ T cells obtained from peripheral blood mononuclear cells (PBMCs) and gastric cancer tissue. RESULTS: Significantly more PD-1+ and Tim-3+ CD8+ T cells in peripheral blood were found in gastric cancer patients than in healthy controls. PD-1+ CD8+ T cells were significantly correlated with Tim-3+ CD8+ T cells in peripheral blood from the gastric cancer patients (r = 0.29, p = 0.036). Furthermore, significantly greater numbers of PD-1+ and Tim-3+ CD8+ T cells were seen in the gastric cancer tissue samples than in the PBMCs. CD8+ T cells positive for both PD-1 and Tim-3 produced significantly less IFN gamma than cells negative for both and cells positive for PD-1 and negative for Tim-3. CONCLUSION: An increased number of PD-1+ and Tim-3+ CD8+ T cells is closely related to impaired function of CD8+ T cells in gastric cancer patients. PMID- 26801347 TI - Melanosomes made from recycling (endosomes): A tubule-stabilizing function revealed for Biogenesis of Lysosome-related Organelles Complex-1. PMID- 26801346 TI - PCR-reverse blot hybridization assay for fast and accurate identification of causative species in superficial fungal infections. AB - BACKGROUND: Superficial fungal infections are a very common problem in dermatological clinics. The diagnostic method of fungal culture is time-consuming and has inconsistent sensitivity. Therefore, a practical method for rapid and accurate identification of the species causing superficial fungal infections is needed. AIM: To compare PCR-reverse blot hybridization assay (PCR-REBA) with conventional fungal diagnostic methods so as to determine the reliability of PCR REBA for the diagnosis and species identification in superficial fungal infections. METHODS: Potassium hydroxide (KOH) preparation, fungal culture, conventional real-time PCR and PCR-REBA were used to assess 83 specimens, and the results from each method were compared. RESULTS: Of the 83 specimens, 44 specimens that were positive by fungal culture had 62.7% agreement with PCR-REBA. Compared with real-time PCR, there was 68.7% agreement with fungal culture, but 91.6% agreement with PCR-REBA. When the comparison was made using the 55 specimens that gave positive results in both KOH preparation and fungal culture, there was 85.5% agreement with real-time PCR for fungal culture, but 94.5% agreement with PCR-REBA. CONCLUSIONS: Compared with KOH preparation or fungal culture, PCR-REBA has higher sensitivity and specificity. Therefore, PCR-REBA could be a useful method in clinical settings because it can identify species quickly and accurately, and can also determine the existence of pathogens. PMID- 26801348 TI - Root-shoot interactions explain the reduction of leaf mineral content in Arabidopsis plants grown under elevated [CO2 ] conditions. AB - Although shoot N depletion in plants exposed to elevated [CO2 ] has already been reported on several occasions, some uncertainty remains about the mechanisms involved. This study illustrates (1) the importance of characterizing root-shoot interactions and (2) the physiological, biochemical and gene expression mechanisms adopted by nitrate-fed Arabidopsis thaliana plants grown under elevated [CO2 ]. Elevated [CO2 ] increases biomass and photosynthetic rates; nevertheless, the decline in total soluble protein, Rubisco and leaf N concentrations revealed a general decrease in leaf N availability. A transcriptomic approach (conducted at the root and shoot level) revealed that exposure to 800 ppm [CO2 ] induced the expression of genes involved in the transport of nitrate and mineral elements. Leaf N and mineral status revealed that N assimilation into proteins was constrained under elevated [CO2 ]. Moreover, this study also highlights how elevated [CO2 ] induced the reorganization of nitrate assimilation between tissues; root nitrogen assimilation was favored over leaf assimilation to offset the decline in nitrogen metabolism in the leaves of plants exposed to elevated [CO2 ]. PMID- 26801349 TI - Erratum to: The Topographic Design of River Channels for Form-Process Linkages. PMID- 26801351 TI - DNA degradation in liquid-based cytology and its comparison with conventional smear. AB - BACKGROUND: In fine needle aspiration biopsy (FNAB) of thyroid nodules, LBC is adopted in most of the hospitals and clinics in Korea for its convenience. BRAF mutation test has been introduced as an important ancillary test, but its applicability has not been completely proven with LBC samples. METHODS: Five aspirates from thyroidectomy specimens were simultaneously processed into LBC and CS slides, in which BRAF mutation tests were performed using three primer sets with PCR products of 72, 164, and 226 base pairs (bp) at 6, 9, and 12 months after processing. In addition, BRAF mutation tests were performed in nine clinical samples that had been prepared by LBC or CS and stored for 3-5 years after processing. RESULTS: At 9 months after processing, LBC failed to provide DNA of sufficient quality for PCR, whereas CS succeeded with primers for amplifying a 226 bp fragment. Furthermore, CS had successful amplification of DNA despite a delay of more than 1 year. The failure of DNA amplification in LBC was overcome by using primers to amplify shorter PCR products, suggesting that DNA degradation occurred in LBC. However, false positive or negative results were observed in primers for amplifying shorter size. The kind of preservative solutions used in LBC did not affect test results. CONCLUSION: LBC may have disadvantages in long-term DNA preservation because of its accelerated DNA degradation compared with alcohol-fixed CS. Using primers to amplify shorter size fragments might be helpful in mitigating loss of signal due to DNA degradation in LBC. PMID- 26801350 TI - Influence of exercise intensity and duration on functional and biochemical perturbations in the human heart. AB - KEY POINTS: Strenuous endurance exercise induces transient functional and biochemical cardiac perturbations that persist for 24-48 h. The magnitude and time-course of exercise-induced reductions in ventricular function and increases in cardiac injury markers are influenced by the intensity and duration of exercise. In a human experimental model, exercise-induced reductions in ventricular strain and increases in cardiac troponin are greater, and persist for longer, when exercise is performed within the heavy- compared to moderate intensity exercise domain, despite matching for total mechanical work. The results of the present study help us better understand the dose-response relationship between endurance exercise and acute cardiac stress/injury, a finding that has implications for the prescription of day-to-day endurance exercise regimes. ABSTRACT: Strenuous endurance exercise induces transient cardiac perturbations with ambiguous health outcomes. The present study investigated the magnitude and time-course of exercise-induced functional and biochemical cardiac perturbations by manipulating the exercise intensity-duration matrix. Echocardiograph-derived left (LV) and right (RV) ventricular global longitudinal strain (GLS), and serum high-sensitivity cardiac troponin (hs-cTnI) concentration, were examined in 10 males (age: 27 +/- 4 years; VO2, peak : 4.0 +/ 0.8 l min(-1) ) before, throughout (50%, 75% and 100%), and during recovery (1, 3, 6 and 24 h) from two exercise trials. The two exercise trials consisted of 90 and 120 min of heavy- and moderate-intensity cycling, respectively, with total mechanical work matched. LVGLS decreased (P < 0.01) during the 90 min trial only, with reductions peaking at 1 h post (pre: -19.9 +/- 0.6%; 1 h post: -18.5 +/- 0.7%) and persisting for >24 h into recovery. RVGLS decreased (P < 0.05) during both exercise trials with reductions in the 90 min trial peaking at 1 h post (pre: -27.5 +/- 0.7%; 1 h post: -25.1 +/- 0.8%) and persisting for >24 h into recovery. Serum hs-cTnI increased (P < 0.01) during both exercise trials, with concentrations peaking at 3 h post but only exceeding cardio-healthy reference limits (14 ng l(-1) ) in the 90 min trial (pre: 4.2 +/- 2.4 ng l(-1) ; 3 h post: 25.1 +/- 7.9 ng l(-1) ). Exercise-induced reductions in ventricular strain and increases in cardiac injury markers persist for 24 h following exercise that is typical of day-to-day endurance exercise training; however, the magnitude and time-course of this response can be altered by manipulating the intensity duration matrix. PMID- 26801352 TI - Overexpression of MdbHLH104 gene enhances the tolerance to iron deficiency in apple. AB - Fe deficiency is a widespread nutritional disorder in plants. The basic helix loop-helix (bHLH) transcription factors (TFs), especially Ib subgroup bHLH TFs which are involved in iron uptake, have been identified. In this study, an IVc subgroup bHLH TF MdbHLH104 was identified and characterized as a key component in the response to Fe deficiency in apple. The overexpression of the MdbHLH104 gene noticeably increased the H(+) -ATPase activity under iron limitation conditions and the tolerance to Fe deficiency in transgenic apple plants and calli. Further investigation showed that MdbHLH104 proteins bonded directly to the promoter of the MdAHA8 gene, thereby positively regulating its expression, the plasma membrane (PM) H(+) -ATPase activity and Fe uptake. Similarly, MdbHLH104 directly modulated the expression of three Fe-responsive bHLH genes, MdbHLH38, MdbHLH39 and MdPYE. In addition, MdbHLH104 interacted with 5 other IVc subgroup bHLH proteins to coregulate the expression of the MdAHA8 gene, the activity of PM H(+) -ATPase and the content of Fe in apple calli. Therefore, MdbHLH104 acts together with other apple bHLH TFs to regulate Fe uptake by modulating the expression of the MdAHA8 gene and the activity of PM H(+) -ATPase in apple. PMID- 26801353 TI - A subset of enteroendocrine cells is activated by amino acids in the Drosophila midgut. AB - The intestine is involved in digestion and absorption, as well as the regulation of metabolism upon sensation of the internal intestinal environment. Enteroendocrine cells are thought to mediate these internal intestinal chemosensory functions. Using the CaLexA (calcium-dependent nuclear import of LexA) method, we examined the enteroendocrine cell populations that are activated when flies are subjected to various dietary conditions such as starvation, sugar, high fat, protein, or pathogen exposure. We find that a specific subpopulation of enteroendocrine cells in the posterior midgut which express Dh31 and tachykinin are activated by the presence of proteins and amino acids. PMID- 26801354 TI - Authors' Reply to Letter to the Editor From Dr. Bliwise (re: "Sleep Architecture and Mental Health Among Community-dwelling Older Men"). PMID- 26801355 TI - Letter to the Editor re. Smagula et al. ("Sleep Architecture and Mental Health Among Community-Dwelling Older Men"). PMID- 26801356 TI - Interventions for hidradenitis suppurativa: a Cochrane systematic review incorporating GRADE assessment of evidence quality. AB - More than 50 interventions have been used to treat hidradenitis suppurativa (HS), and so therapy decisions can be challenging. Our objective was to summarize and appraise randomized controlled trial (RCT) evidence for HS interventions in adults. Searches were conducted in Medline, Embase, CENTRAL, LILACS, five trials registers and abstracts from eight dermatology conferences until 13 August 2015. Two review authors independently assessed study eligibility, extracted data and assessed methodological quality. Primary outcomes were quality of life and adverse effects of the interventions. Twelve trials, from 1983 to 2015, investigating 15 different interventions met our inclusion criteria. The median trial duration was 16 weeks and the median number of participants was 27. Adalimumab 40 mg weekly improved the Dermatology Life Quality Index (DLQI) by 4.0 points, which equates to the minimal clinically important difference for the scale, compared with placebo (95% confidence interval -6.5 to -1.5 points). Evidence quality was reduced to 'moderate' because the results are based on only a single study. Adalimumab 40 mg every other week was ineffective in a meta analysis of two studies comprising 124 participants. Infliximab 5 mg kg(-1) improved the DLQI score by 8.4 points after 8 weeks in a moderate-quality study completed by 33 of 38 participants. Etanercept 50 mg twice weekly was ineffective. Inclusion of a gentamicin sponge prior to primary closure did not improve outcomes. Other interventions, including topical and oral antibiotics, were investigated by relatively small studies, preventing treatment recommendations due to imprecision. More, larger RCTs are required to investigate most HS interventions, particularly oral treatments and surgical therapy. Moderate-quality evidence suggests that adalimumab given weekly and infliximab are effective, whereas adalimumab every other week is ineffective. PMID- 26801357 TI - Students' perceptions of vertical and horizontal integration in a discipline based dental school. AB - INTRODUCTION: Integration is a key concern in discipline-based undergraduate dental curricula. Therefore, this study compared feedback on integration from students who participated in different instructional designs in a Comprehensive Patient Care course. METHODS: The study was conducted at the University of Pretoria (2009-2011). Third-year cohorts (Cohorts A, B and C) participated in pre clinical case-based learning, whilst fourth-year cohorts (Cohorts D and E) received didactic teaching in Comprehensive Patient Care. Cohorts A, D and E practised clinical Comprehensive Patient Care in a discipline-based clinic. Cohort B conducted their Comprehensive Patient Care patient examinations in a dedicated facility supervised by dedicated faculty responsible to teach integration. Students had to indicate on visual analogue scales whether the way they were taught at the school helped them to integrate knowledge from the same (horizontal integration) and preceding (vertical integration) year of study. The end-points of the scales were defined as 'definitely' and 'not at all'. Analysis of variance (ANOVA) was employed to measure the differences between cohorts according to the year of study. RESULTS: Third-year case-based learning cohorts rated the horizontal integration close to 80/100 and vertical integration ranging from 64 to 71/100. In year four, Cohort B rated vertical and horizontal integration 9-15% higher (ANOVA, P < 0.05) than Cohorts A and D. In year five, Cohort A rated vertical and horizontal integration 11-18% higher (ANOVA, P < 0.05) than Cohorts D and E. CONCLUSION: Pre-clinical case-based learning and Comprehensive Patient Care supervised by dedicated faculty were associated with more favourable perceptions about integration in the discipline-based undergraduate dental curriculum. PMID- 26801358 TI - A Comparison of the Effect of Interposed Abdominal Compression Cardiopulmonary Resuscitation and Standard Cardiopulmonary Resuscitation Methods on End-tidal CO2 and the Return of Spontaneous Circulation Following Cardiac Arrest: A Clinical Trial. AB - OBJECTIVES: Sudden cardiac arrest is a major cause of death in the adult population of developed countries, with only 10%-15% of cardiopulmonary resuscitations (CPRs) being successful. We aimed to compare the effects of interposed abdominal compression CPR (IAC-CPR) with standard CPR (STD-CPR) methods on end-tidal CO2 (ETCO2 ) and the return of spontaneous circulation (ROSC) following cardiac arrest in a hospital setting. METHODS: After cardiac arrest was confirmed in a patient at Mashhad Ghaem Hospital, 80 cases were randomly assigned to one of the two methods of resuscitation, either IAC-CPR or STD-CPR, respectively. The inclusion criteria for the study were nontraumatic cardiac arrest, in patients between the age of 18 and 85 years, and the presence of endotracheal tube. Exclusion criteria were abdominal surgery in the past 2 weeks, active gastrointestinal bleeding, pulmonary embolism, and suspected pregnancy. RESULTS: There was a significant difference between the two groups in ETCO2 (p < 0.003), but there was no significant difference as far as the ROSC (p > 0.50). CONCLUSION: The increase in the ETCO2 during IAC-CPR is an indicator of the increase in cardiac output following the use of this method of CPR. PMID- 26801359 TI - Direct Dynamic Kinetic Analysis and Computer Simulation of Growth of Clostridium perfringens in Cooked Turkey during Cooling. AB - This research applied a new 1-step methodology to directly construct a tertiary model that describes the growth of Clostridium perfringens in cooked turkey meat under dynamically cooling conditions. The kinetic parameters of the growth models were determined by numerical analysis and optimization using multiple dynamic growth curves. The models and kinetic parameters were validated using independent growth curves obtained under various cooling conditions. The results showed that the residual errors (epsilon) of the predictions followed a Laplace distribution that is symmetric with respect to epsilon = 0. For residual errors, 90.6% are within +/-0.5 Log CFU/g and 73.4% are +/-0.25 Log CFU/g for all growth curves used for validation. For relative growth <1.0 Log CFU/g, 88.9% of the residual errors are within +/-0.5 Log CFU/g, and 63.0% are within +/-0.25 Log CFU/g. For relative growth of <2.0 Log CFU/g, 92.7% of the residual errors are within +/-0.5 Log CFU/g, and 70.3% are within +/-0.25 Log CFU/g. The scale and distribution of residual errors clearly suggests that the models and estimated kinetic parameters are reasonably accurate in predicting the growth of C. perfringens. Monte Carlo simulation was used to estimate the probabilities of >1.0 and 2.0 Log CFU/g relative growth of C. perfringens in the final products at the end of cooling. This probabilistic process analysis approach provides a new alternative for estimating and managing the risk of a product and can help the food industry and regulatory agencies assess the safety of cooked meat in the event of cooling deviation. PMID- 26801361 TI - [Pulmonary alterations in Hodgkin lymphoma]. AB - Most of Hodgkin lymphoma patients survive due to combined chemo/radiotherapy. Improved survival brings long-term side effects to the front, which may determine the patients' subsequent quality of life and expected lifetime. This manuscript aims to analyze lung manifestations of Hodgkin lymphoma and treatment related pulmonary complications, demonstrated with own cases. The lung involvement in Hodgkin lymphoma is often secondary, and primary pulmonary involvement is very rare. The authors found 8-12% of lung involvement among their patients. Side effects of treatment consist of pulmonary infections in conjuction with immunosuppression, while on the other hand bleomycin and chest irradiation as part of current standard of care induced pneumonitis and fibrosis are reported. The pulmonary involvement in Hodgkin lymphoma may cause differential diagnostic difficulty. Lung involvement could modify stage and consequently treatment, and the development of side effects might determine later quality of life and expected lifetime. Therefore, identification of lung involvement is crucial. PMID- 26801360 TI - BioNano genome mapping of individual chromosomes supports physical mapping and sequence assembly in complex plant genomes. AB - The assembly of a reference genome sequence of bread wheat is challenging due to its specific features such as the genome size of 17 Gbp, polyploid nature and prevalence of repetitive sequences. BAC-by-BAC sequencing based on chromosomal physical maps, adopted by the International Wheat Genome Sequencing Consortium as the key strategy, reduces problems caused by the genome complexity and polyploidy, but the repeat content still hampers the sequence assembly. Availability of a high-resolution genomic map to guide sequence scaffolding and validate physical map and sequence assemblies would be highly beneficial to obtaining an accurate and complete genome sequence. Here, we chose the short arm of chromosome 7D (7DS) as a model to demonstrate for the first time that it is possible to couple chromosome flow sorting with genome mapping in nanochannel arrays and create a de novo genome map of a wheat chromosome. We constructed a high-resolution chromosome map composed of 371 contigs with an N50 of 1.3 Mb. Long DNA molecules achieved by our approach facilitated chromosome-scale analysis of repetitive sequences and revealed a ~800-kb array of tandem repeats intractable to current DNA sequencing technologies. Anchoring 7DS sequence assemblies obtained by clone-by-clone sequencing to the 7DS genome map provided a valuable tool to improve the BAC-contig physical map and validate sequence assembly on a chromosome-arm scale. Our results indicate that creating genome maps for the whole wheat genome in a chromosome-by-chromosome manner is feasible and that they will be an affordable tool to support the production of improved pseudomolecules. PMID- 26801362 TI - [Active euthanasia in Colombia and assisted suicide in California]. AB - The institution of active euthanasia has been legal in Colombia since 2015. In California, the regulation on physician-assisted suicide will come into effect on January 1, 2016. The legal institution of active euthanasia is not accepted under the law of the United States of America, however, physician-assisted suicide is accepted in an increasing number of member states. The related regulation in Oregon is imitated in other member states. In South America, Colombia is not the first country to legalize active euthanasia: active euthanasia has been legal in Uruguay since 1932. The North American legal tradition markedly differs from the South American one and both are incompatible with the Central European rule of law. In Hungary and in most European Union countries, solely the passive form of euthanasia is legal. In the Benelux countries, the active form of euthanasia is legal because the supranational law of the European Union does not prohibit it. Notwithstanding, European Union law does not prescribe legalization of either the active form of euthanasia, or the physician-assisted suicide. PMID- 26801363 TI - [A novel surgical mesh suitable for laparoscopy, studied on animal model]. AB - INTRODUCTION: Reconstruction of the abdominal wall with mesh is a widely used surgical procedure. The non-absorbable meshes tend to cause numerous side effects. AIM: The aim of the author was to produce an absorbable, polymer-based mesh that possesses appropriate chemical, mechanical and biological properties. METHOD: A three-dimensional, biocompatible mesh was produced from poly-vinyl alcohol using reactive electrospinning. Toxicity and cell-mesh interactions were tested using human lung carcinoma epithelial cells (A-549), and in vivo tests were conducted in 42 male Wistar rats at the 1-5, 7 and 14 postoperative days (3 rats/groups). RESULTS: In the in vitro tests poly-vinyl-alcohol was biocompatible. In the in vivo tests no major complication was associated with the mesh made of poly-vinyl-alcohol. CONCLUSIONS: The author concludes that this polymer mesh is biocompatible, it does not damage the surrounding tissues and integrates well with them. PMID- 26801364 TI - [The role of laparoscopy in cholecystectomy in patients 80 years old and older]. AB - INTRODUCTION: The incidence of cholelithiasis increases with age, however, there is still little data about the outcomes of cholecystectomy in patients with age of 80 and above. Population ageing presents tremendous challenges for surgeons. AIM: The aim of the authors was to compare emergency and elective cholecystectomies performed in these elderly patients. METHOD: This retrospective study was based on the analysis of operation type, conversion rate, complications, mortality, length of hospital stay of all patients over 80 who underwent cholecystectomy in the last 6 years at the 1st Department of Surgery, Semmelweis University. RESULTS: 69 elective and 51 emergency operations were performed. In the emergency group pancreatitis was found in 9.8%, liver abscess in 14%, and common bile duct stones in 27% of the patients on admission. Laparoscopic cholecystectomy could be performed in 84% of patients in the elective group, while in 17.7% of patients in the emergency group. The length of stay at the intensive care unit was 9.1 and 1 days, while the total length of hospital stay was 12 and 3.6 days for the elective and emergency groups, respectively. In the emergency group mortality was 20% and reoperation was performed in 16% of patients, while at the elective group none of these occurred. CONCLUSION: Laparoscopic cholecystectomy is safe as elective surgery for patients with age of 80 and above. For this reason the authors recommend elective cholecystectomy in this age group. PMID- 26801366 TI - [Prof. Dr. Otto Ribari (1932-2015)]. PMID- 26801365 TI - [Recurrent acute myocardial infarction as a thromboembolic complication of atrial fibrillation]. AB - Coronary thromboembolism with subsequent myocardial infarction is a rare complication of atrial fibrillation. The authors present the history of a 55-year old male with a history of acute myocardial infarction caused by thromboembolism in the distal part of left anterior descending coronary artery and paroxysmal atrial fibrillation, who presented one year later with new chest pain, ST-segment elevation and atrial fibrillation. Coronarography confirmed the presence of thrombus in the circumflex coronary artery. Transesophageal echocardiogram showed left atrial appendage thrombus. To the knowledge of the authors this is the first report of recurrent myocardial infarction caused by atrial fibrillation. PMID- 26801368 TI - Ultrasound-guided assessment of thyroid nodules based on the 2014 British Thyroid Association guidelines for the management of thyroid cancer - how we do it. PMID- 26801369 TI - Peptides with dual mode of action: Killing bacteria and preventing endotoxin induced sepsis. AB - Bacterial infections, with the most severe form being sepsis, can often not be treated adequately leading to high morbidity and lethality of infected patients in critical care units. In particular, the increase in resistant bacterial strains and the lack of new antibiotics are main reasons for the worsening of the current situation, As a new approach, the use of antimicrobial peptides (AMPs) seems to be promising, combining the ability of broad-spectrum bactericidal activity and low potential of induction of resistance. Peptides based on natural defense proteins or polypeptides such as lactoferrin, Limulus anti lipopolysaccharide factor (LALF), cathelicidins, and granulysins are candidates due to their high affinity to bacteria and to their pathogenicity factors, in first line lipopolysaccharide (LPS, endotoxin) of Gram-negative origin. In this review, we discuss literature with the focus on the use of AMPs from natural sources and their variants as antibacterial as well as anti-endotoxin (anti inflammatory) drugs. Considerable progress has been made by the design of new AMPs for acting efficiently against the LPS-induced inflammation reaction in vitro as well as in vivo (mouse) models of sepsis. Furthermore, the data indicate that efficient antibacterial compounds are not necessarily equally efficient as anti-endotoxin drugs and vice versa. The most important reason for this may be the different molecular geometry of LPS in bacteria and in free form. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert. PMID- 26801370 TI - The association of defensin HNP-2 with negatively charged membranes: A combined fluorescence and linear dichroism study. AB - The association of defensin HNP-2 with negatively charged membranes has been studied using a new approach that combines fluorescence and linear dichroism (LD) spectroscopies with simulated LD spectra in order to characterise the binding kinetics and bound configurations of the peptide. Binding to membranes composed of mixtures of diacylglycerophosphocholines (PC) with either diacylglycerophosphoglycerol (PG) or diacylglycerophosphoserine (PS) was conducted at lipid:peptide ratios that yielded binding, but not membrane fusion. HNP-2 association with membranes under these conditions was a 2 stage-process, with both stages exhibiting first order kinetics. The fast initial step, with a half-life of < 1 min, was followed by a slower step with a half-life of > 3 min. Conversion between the states was estimated to have an enthalpy of activation of approximately 10 kJ mol(-1) and an entropy of activation of -0.2 kJ K mol(-1). LD spectra corresponding to each of the membrane bound states were generated by non linear regression using a standard kinetic model. These spectra are interpreted in comparison with spectra calculated using the program Dichrocalc and reveal that the peptide associates with membranes in a small number of stable configurations. All of these configurations have a significant proportion of beta sheet structure residing in the plane of the membrane. Two configurations support structures previously proposed for defensins in membranes. PMID- 26801372 TI - Cardiovascular Effects of Marijuana. PMID- 26801371 TI - Should human milk for premature children be fortified after discharge to improve neurodevelopmental outcomes? PMID- 26801373 TI - Hymenobacter paludis sp. nov., isolated from a marsh. AB - A bacterial strain, designated KBP-30T, was isolated from a water sample taken from the Banping Lake Wetland Park in Taiwan and characterized taxonomically using a polyphasic approach. Cells of strain KBP-30T were Gram-stain-negative, aerobic, motile by gliding rods that were covered by large capsules and formed red colonies. Growth occurred at 10-37 degrees C (optimum 20 degrees C), at pH 6-8 (optimum pH 6) and with 0-1 % NaCl (optimum 0 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain KBP-30T belonged to the genus Hymenobacter and was most closely related to Hymenobacter ocellatus Myx 2105T with a sequence similarity of 97.7 %; 16S rRNA gene sequence similarities were less than 95.1 % with other members of the genus. Strain KBP-30T contained iso C15 : 0, summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B), anteiso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) as the predominant fatty acids. The major isoprenoid quinone was MK-7. The polar lipid profile consisted of phosphatidylethanolamine, three unidentified aminophospholipids, an unidentified aminolipid, an unidentified glycolipid and eight unidentified lipids. The major polyamine was homospermidine. The DNA G+C content of the genomic DNA was 60.3 mol%. The DNA-DNA relatedness of strain KBP 30T with respect to Hymenobacter ocellatus Myx 2105T was less than 42 %. On the basis of the phylogenetic inference and phenotypic data, strain KBP-30T represents a novel species of the genus Hymenobacter, for which the name Hymenobacter paludis sp. nov. is proposed. The type strain is KBP-30T ( = LMG 27293T = KCTC 32237T). PMID- 26801374 TI - Researchers must share data to ensure publication in top journals. PMID- 26801376 TI - Male With Severe Abdominal Pain. Atraumatic splenic rupture in the setting of splenic vein thrombosis. PMID- 26801375 TI - Outcomes after endoscopic versus surgical therapy for early esophageal cancers in an older population. AB - BACKGROUND AND AIMS: Endoscopic treatment of early esophageal cancer provides an alternative to esophagectomy, which older patients may not tolerate. Population based data regarding short-term outcomes and recurrence after endoscopic treatment for esophageal cancer are limited. We compared short-term outcomes, treated recurrence, and survival after endoscopic versus surgical therapy for early esophageal cancers in an older population. METHODS: We conducted a retrospective cohort study identifying patients aged >=66 years with Tis or T1a tumors without nodal involvement diagnosed from 1994 to 2011 from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. RESULTS: Of 2193 patients, 41% (n = 893) underwent esophagectomy, and 12% (n = 255) underwent endoscopic treatment within 6 months of diagnosis. Those treated endoscopically were older and more likely to have a Charlson comorbidity score >=2. A composite endpoint, hospitalization and/or adverse events at 60 days, was higher in surgical patients than in the endoscopic treatment group (30% vs 12%; P < .001). In a Cox model stratified by histology, adjusting for other factors, endoscopic treatment was associated with improved 2-year survival (hazard ratio 0.51; 95% CI, 0.36-0.73). CONCLUSIONS: In this older population, a composite short-term endpoint was worse in the surgical group. Endoscopic treatment was associated with improved survival through 2 years. These results suggest that endoscopic treatment is a reasonable approach for early esophageal cancers in the elderly. PMID- 26801377 TI - Child With Dinner Fork Deformity. Distal radius fracture. PMID- 26801378 TI - Commentary: Where We're Going, We Don't Need Roads. PMID- 26801379 TI - Less Than 5 Minutes. PMID- 26801381 TI - ANNALS OF EMERGENCY MEDICINE JOURNAL CLUB. Move Over Morphine: Is Ketamine an Effective and Safe Alternative for Treating Acute Pain?: Answers to the September 2015 Journal Club. PMID- 26801382 TI - Man With Acute Respiratory Distress. Tricuspid vegetation concerning for infective endocarditis. PMID- 26801383 TI - An Unusual Cause of Limp in a Toddler. Talar osteomyelitis. PMID- 26801384 TI - Limping Child? Think LIMPSS. PMID- 26801385 TI - External Validation of the STONE Score. PMID- 26801386 TI - In reply. PMID- 26801387 TI - Out-of-Hospital Use of Analgesia and Sedation. PMID- 26801388 TI - Young Woman With Vaginal Bleeding. Uterine artery pseudoaneurysm. PMID- 26801389 TI - The impact of taphonomic data on phylogenetic resolution: Helenodora inopinata (Carboniferous, Mazon Creek Lagerstatte) and the onychophoran stem lineage. AB - BACKGROUND: The origin of the body plan of modern velvet worms (Onychophora) lies in the extinct lobopodians of the Palaeozoic. Helenodora inopinata, from the Mazon Creek Lagerstatte of Illinois (Francis Creek Shale, Carbondale Formation, Middle Pennsylvanian), has been proposed as an intermediate between the "weird wonders" of the Cambrian seas and modern terrestrial predatory onychophorans. The type material of H. inopinata, however, leaves much of the crucial anatomy unknown. RESULTS: Here we present a redescription of this taxon based on more complete material, including new details of the head and posterior portion of the trunk, informed by the results of experimental decay of extant onychophorans. H. inopinata is indeed best resolved as a stem-onychophoran, but lacks several key features of modern velvet worms including, crucially, those that would suggest a terrestrial mode of life. CONCLUSIONS: The presence of H. inopinata in the Carboniferous demonstrates the survival of a Cambrian marine morphotype, and a likely post-Carboniferous origin of crown-Onychophora. Our analysis also demonstrates that taphonomically informed tests of character interpretations have the potential to improve phylogenetic resolution. PMID- 26801390 TI - Angiotensin II (de)sensitization: Fluid intake studies with implications for cardiovascular control. AB - Cardiovascular disease is the leading cause of death worldwide and hypertension is the most common risk factor for death. Although many anti-hypertensive pharmacotherapies are approved for use in the United States, rates of hypertension have increased over the past decade. This review article summarizes a presentation given at the 2015 meeting of the Society for the Study of Ingestive Behavior. The presentation described work performed in our laboratory that uses angiotensin II-induced drinking as a model system to study behavioral and cardiovascular effects of the renin-angiotensin system, a key component of blood pressure regulation, and a common target of anti-hypertensives. Angiotensin II (AngII) is a potent dipsogen, but the drinking response shows a rapid desensitization after repeated injections of AngII. This desensitization appears to be dependent upon the timing of the injections, requires activation of the AngII type 1 (AT1) receptor, requires activation of mitogen-activated protein (MAP) kinase family members, and involves the anteroventral third ventricle (AV3V) region as a critical site of action. Moreover, the response does not appear to be the result of a more general suppression of behavior, a sensitized pressor response to AngII, or an aversive state generated by the treatment. More recent studies suggest that the treatment regimen used to produce desensitization in our laboratory also prevents the sensitization that occurs after daily bolus injections of AngII. Our hope is that these findings can be used to support future basic research on the topic that could lead to new developments in treatments for hypertension. PMID- 26801391 TI - Pinealectomy abolishes circadian behavior and interferes with circadian clock gene oscillations in brain and liver but not retina in a migratory songbird. AB - In songbirds, the pineal gland is part of the multi-oscillatory circadian timing system, with participating component oscillators in the eyes and hypothalamus. This study investigated the role of the pineal gland in development of the nighttime migratory restlessness (Zugunruhe) and generation of circadian gene oscillations in the retina, brain and liver tissues in migratory redheaded buntings (Emberiza bruniceps). Pinealectomized (pinx) and sham-operated buntings entrained to short days (8h light: 16h darkness, 8L:16D) were sequentially exposed for 10days each to stimulatory long days (13L: 11D) and constant dim light (LLdim; a condition that tested circadian rhythm persistence). Whereas activity-rest pattern was monitored continuously, the mRNA expressions of clock genes (bmal1, clock, npas2, per2, cry1, roralpha, reveralpha) were measured in the retina, hypothalamus, telencephalon, optic tectum and liver tissues at circadian times, CT, 1, 6, 13, 17 and 21 (CT 0, activity onset) on day 11 of the LLdim. The absence of the pineal gland did not affect the development of long-day induced Zugunruhe but caused decay of the circadian rhythm in Zugunruhe as well as the clock gene oscillations in the hypothalamus, but not in the retina. Further, there were variable effects of pinealectomy in the peripheral brain and liver tissue circadian gene oscillations, notably the persistence of per 2 and cry1 (optic tectum), roralpha (telencephalon) and npas2 (liver) mRNA oscillations in pinx birds. We suggest the pineal gland dependence of the generation of circadian gene oscillations in the hypothalamus, not retina, and peripheral brain and liver tissues in migratory redheaded buntings. PMID- 26801392 TI - Balloon Guide Catheter in Complex Anterior Circulation Mechanical Thrombectomy: Beyond Proximal Occlusion and Flow Reversal. PMID- 26801393 TI - Correlation between Activity and Domain Complementation in Adenylyl Cyclase Demonstrated with a Novel Fluorescence Resonance Energy Transfer Sensor. AB - Adenylyl cyclase (AC) activity relies on multiple effectors acting through distinct binding sites. Crystal structures have revealed the location of these sites, and biochemical studies have explored the kinetics of ACs, but the interplay between conformation and activity remains incompletely understood. Here, we describe a novel fluorescence resonance energy transfer (FRET) sensor that functions both as a soluble cyclase and a reporter of complementation within the catalytic domain. We report a strong linear correlation between catalytic domain complementation and cyclase activity upon stimulation with forskolin and Galphas. Exploiting this, we dissect the mechanism of action of a series of forskolin analogs and a P-site inhibitor, 2'-d3'-AMP. Finally, we demonstrate that this sensor is functional in live cells, wherein it reports forskolin stimulated activity of AC. PMID- 26801394 TI - Effectiveness of the "Cancer Home-Life Intervention" on everyday activities and quality of life in people with advanced cancer living at home: a randomised controlled trial and an economic evaluation. AB - BACKGROUND: During the past decade an increasing number of people live with advanced cancer mainly due to improved medical treatment. Research has shown that many people with advanced cancer have problems with everyday activities, which have negative impact on their quality of life, and that they spend a considerable part of their time at home. Still, research on interventions to support the performance of and participation in everyday activities is only scarcely available. Therefore, the occupational therapy-based "Cancer Home-Life Intervention" consisting of tailored adaptive interventions applied in the participant's home environment was developed. The objective of this study is to examine the effectiveness and cost-effectiveness of the Cancer Home-Life Intervention compared to usual care on the performance of and participation in everyday activities and quality of life in people with advanced cancer living at home. METHODS: The study is a randomised, controlled trial (RCT) including an economic evaluation. The required sample size of 272 adults living at home will be recruited from outpatient clinics at two Danish hospitals. They should be diagnosed with cancer; evaluated incurable by the responsible oncologist; and with a functional level 1-2 on the WHO performance scale. The primary outcome is the quality of performance of activities of daily living. Secondary outcomes are problems with prioritised everyday activities; autonomy and participation; and health-related quality of life. Participants are randomly assigned to: a) The Cancer Home-Life Intervention in addition to usual care, and b) Usual care alone. DISCUSSION: The trial will show whether the Cancer Home-Life Intervention provides better support for people with advanced cancer living at home in performing and participating in everyday activities, and whether it contributes to their health-related quality of life. The economic evaluation alongside the RCT will show if the Cancer Home-Life Intervention is cost-effective. The trial will also show the acceptability of the intervention to the target group, and whether subgroups of participants will benefit more than others. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02356627. Registered 02/02/2015. PMID- 26801395 TI - Concurrent validity and test-retest reliability of the Virtual Peg Insertion Test to quantify upper limb function in patients with chronic stroke. AB - BACKGROUND: Measuring arm and hand function of the affected side is vital in stroke rehabilitation. Therefore, the Virtual Peg Insertion Test (VPIT), an assessment combining virtual reality and haptic feedback during a goal-oriented task derived from the Nine Hole Peg Test (NHPT), was developed. This study aimed to evaluate (1) the concurrent validity of key outcome measures of the VPIT, namely the execution time and the number of dropped pegs, with the NHPT and Box and Block Test (BBT), and (2) the test-retest-reliability of these parameters together with the VPIT's additional kinetic and kinematic parameters in patients with chronic stroke. The three tests were administered on 31 chronic patients with stroke in one session (concurrent validity), and the VPIT was retested in a second session 3-7 days later (test-retest reliability). Spearman rank correlation coefficients (rho) were calculated for assessing concurrent validity, and intraclass correlation coefficients (ICCs) were used to determine relative reliability. Bland-Altman plots were drawn and the smallest detectable difference (SDD) was calculated to examine absolute reliability. RESULTS: For the 31 included patients, 11 were able to perform the VPIT solely via use of their affected arm, whereas 20 patients also had to utilize support from their unaffected arm. For n = 31, the VPIT showed low correlations with the NHPT (rho = 0.31 for time (Tex[s]); rho = 0.21 for number of dropped pegs (Ndp)) and BBT (rho = -0.23 for number of transported cubes (Ntc); rho = -0.12 for number of dropped cubes (Ndc)). The test-retest reliability for the parameters Tex[s], mean grasping force (Fggo[N]), number of zero-crossings (Nzc[1/sgo/return) and mean collision force (Fcmean[N]) were good to high, with ICCs ranging from 0.83 to 0.94. Fair reliability could be found for Fgreturn (ICC = 0.75) and trajectory error (Etrajgo[cm]) (0.70). Poor reliability was measured for Etrajreturn[cm] (0.67) and Ndp (0.58). The SDDs were: Tex = 70.2 s, Ndp = 0.4 pegs; Fggo/return = 3.5/1.2 Newton; Nzc[1/s]go/return = 0.2/1.8 zero-crossings; Etrajgo/return = 0.5/0.8 cm; Fcmean = 0.7 Newton. CONCLUSIONS: The VPIT is a promising upper limb function assessment for patients with stroke requiring other components of upper limb motor performance than the NHPT and BBT. The high intra-subject variation indicated that it is a demanding test for this stroke sample, which necessitates a thorough introduction to this assessment. Once familiar, the VPIT provides more objective and comprehensive measurements of upper limb function than conventional, non-computerized hand assessments. PMID- 26801396 TI - Heparan sulfate proteoglycans mediate Abeta-induced oxidative stress and hypercontractility in cultured vascular smooth muscle cells. AB - BACKGROUND: Substantial evidence suggests that amyloid-beta (Abeta) species induce oxidative stress and cerebrovascular (CV) dysfunction in Alzheimer's disease (AD), potentially contributing to the progressive dementia of this disease. The upstream molecular pathways governing this process, however, are poorly understood. In this report, we examine the role of heparan sulfate proteoglycans (HSPG) in Abeta-induced vascular smooth muscle cell (VSMC) dysfunction in vitro. RESULTS: Our results demonstrate that pharmacological depletion of HSPG (by enzymatic degradation with active, but not heat inactivated, heparinase) in primary human cerebral and transformed rat VSMC mitigates Abeta(1-40-) and Abeta(1-42-)induced oxidative stress. This inhibitory effect is specific for HSPG depletion and does not occur with pharmacological depletion of other glycosaminoglycan (GAG) family members. We also found that Abeta(1-40) (but not Abeta(1-42)) causes a hypercontractile phenotype in transformed rat cerebral VSMC that likely results from a HSPG-mediated augmentation in intracellular Ca(2+) activity, as both Abeta(1-40-)induced VSMC hypercontractility and increased Ca(2+) influx are inhibited by pharmacological HSPG depletion. Moreover, chelation of extracellular Ca(2+) with ethylene glycol tetraacetic acid (EGTA) does not prevent the production of Abeta(1-40-) or Abeta(1-42-)mediated reactive oxygen species (ROS), suggesting that Abeta-induced ROS and VSMC hypercontractility occur through different molecular pathways. CONCLUSIONS: Taken together, our data indicate that HSPG are critical mediators of Abeta-induced oxidative stress and Abeta(1-40-)induced VSMC dysfunction. PMID- 26801397 TI - SeqTools: visual tools for manual analysis of sequence alignments. AB - BACKGROUND: Manual annotation is essential to create high-quality reference alignments and annotation. Annotators need to be able to view sequence alignments in detail. The SeqTools package provides three tools for viewing different types of sequence alignment: Blixem is a many-to-one browser of pairwise alignments, displaying multiple match sequences aligned against a single reference sequence; Dotter provides a graphical dot-plot view of a single pairwise alignment; and Belvu is a multiple sequence alignment viewer, editor, and phylogenetic tool. These tools were originally part of the AceDB genome database system but have been completely rewritten to make them generally available as a standalone package of greatly improved function. FINDINGS: Blixem is used by annotators to give a detailed view of the evidence for particular gene models. Blixem displays the gene model positions and the match sequences aligned against the genomic reference sequence. Annotators use this for many reasons, including to check the quality of an alignment, to find missing/misaligned sequence and to identify splice sites and polyA sites and signals. Dotter is used to give a dot-plot representation of a particular pairwise alignment. This is used to identify sequence that is not represented (or is misrepresented) and to quickly compare annotated gene models with transcriptional and protein evidence that putatively supports them. Belvu is used to analyse conservation patterns in multiple sequence alignments and to perform a combination of manual and automatic processing of the alignment. High-quality reference alignments are essential if they are to be used as a starting point for further automatic alignment generation. CONCLUSIONS: While there are many different alignment tools available, the SeqTools package provides unique functionality that annotators have found to be essential for analysing sequence alignments as part of the manual annotation process. PMID- 26801399 TI - Recruitment of bundle branches with permanent His bundle pacing in a patient with advanced conduction system disease: What is the mechanism? PMID- 26801398 TI - Characterization of the Discriminative Stimulus Effects of a NOP Receptor Agonist Ro 64-6198 in Rhesus Monkeys. AB - Nociceptin/orphanin FQ receptor (NOP) agonists have been reported to produce antinociceptive effects in rhesus monkeys with comparable efficacy to MU-opioid receptor (MOP) agonists, but without their limiting side effects. There are also known to be species differences between rodents and nonhuman primates (NHPs) in the behavioral effects of NOP agonists. The aims of this study were the following: 1) to determine if the NOP agonist Ro 64-6198 could be trained as a discriminative stimulus; 2) to evaluate its pharmacological selectivity as a discriminative stimulus; and 3) to establish the order of potency with which Ro 64-6198 produces discriminative stimulus effects compared with analgesic effects in NHPs. Two groups of rhesus monkeys were trained to discriminate either fentanyl or Ro 64-6198 from vehicle. Four monkeys were trained in the warm-water tail-withdrawal procedure to measure antinociception. Ro 64-6198 produced discriminative stimulus effects that were blocked by the NOP antagonist J-113397 and not by naltrexone. The discriminative stimulus effects of Ro 64-6198 partially generalized to diazepam, but not to fentanyl, SNC 80, ketocyclazocine, buprenorphine, phencyclidine, or chlorpromazine. Fentanyl produced stimulus effects that were blocked by naltrexone and not by J-113397, and Ro 64-6198 did not produce fentanyl-appropriate responding in fentanyl-trained animals. In measures of antinociception, fentanyl, but not Ro 64-6198, produced dose dependent increases in tail-withdrawal latency. Together, these results demonstrate that Ro 64-6198 produced stimulus effects in monkeys that are distinct from other opioid receptor agonists, but may be somewhat similar to diazepam. In contrast to previous findings, Ro 64-6198 did not produce antinociception in the majority of animals tested even at doses considerably greater than those that produced discriminative stimulus effects. PMID- 26801400 TI - Elderly woman with regularized atrial fibrillation. PMID- 26801401 TI - Proceedings from Heart Rhythm Society's emerging technologies forum, Boston, MA, May 12, 2015. AB - Physicians are in an excellent position to significantly contribute to medical device innovation, but the process of bringing an idea to the bedside is complex. To begin to address these perceived barriers, the Heart Rhythm Society convened a forum of stakeholders in medical device innovation in conjunction with the 2015 Heart Rhythm Society Annual Scientific Sessions. The forum facilitated open discussion on medical device innovation, including obstacles to physician involvement and possible solutions. This report is based on the themes that emerged. First, physician innovators must take an organized approach to identifying unmet clinical needs and potential solutions. Second, extensive funds, usually secured through solicitation for investment, are often required to achieve meaningful progress, developing an idea into a device. Third, planning for regulatory requirements of the US Food and Drug Administration and Centers for Medicare & Medicaid Services is essential. In addition to these issues, intellectual property and overall trends in health care, including international markets, are critically relevant considerations for the physician innovator. Importantly, there are a number of ways in which professional societies can assist physician innovators to navigate the complex medical device innovation landscape, bring clinically meaningful devices to market more quickly, and ultimately improve patient care. These efforts include facilitating interaction between potential collaborators through scientific meetings and other gatherings; collecting, evaluating, and disseminating state-of-the-art scientific information; and representing the interests of members in interactions with regulators and policymakers. PMID- 26801402 TI - Effectiveness of additional follow-up telephone counseling in a smoking cessation clinic in Beijing and predictors of quitting among Chinese male smokers. AB - BACKGROUND: No previous studies have investigated whether additional telephone follow-up counseling sessions after face-to-face counseling can increase quitting in China, and whether this strategy is feasible and effective for promoting smoking cessation is still unclear. METHODS: A non-randomized controlled study was conducted in Beijing. We compared the quit rates of one group which received face-to-face counseling (FC) alone (one session of 40 min) to another group which received the same face-to-face counseling plus four follow-up sessions of brief telephone counseling (15-20 min each) at 1 week, 1, 3 and 6 month follow-up (FCF). No smoking cessation medication was provided. From October 2008 to August 2013, Chinese male smokers who sought treatment in a part-time regular smoking cessation clinic of a large general hospital in Beijing were invited to participate in the present study. Eligible male smokers (n = 547) were divided into two groups: FC (n = 149) and FCF (n = 398). Main outcomes were self-reported 7-day point prevalence and 6 month continuous quit rates at 12 month follow-up. RESULTS: By intention to treat, at 12 month follow-up, the 7-day point prevalence and 6 month continuous quit rates of FC and FCF were 14.8 % and 26.4 %, and 10.7 % and 19.6 % respectively. The adjusted odds ratios (95 % confidence intervals) of quitting in FCF compared to FC was 2.34 (1.34-4.10) (P = 0.003) and 2.41 (1.28 4.52) (P = 0.006), respectively. Stepwise logistic regression showed that FCF, being married, unemployed and a lower Fagerstrom score were significant independent predictors of 6 month continuous quitting at 12 month follow-up. CONCLUSIONS: Using systematically collected data from real-world practice, our smoking cessation clinic has shown that the additional telephone follow-up counseling sessions doubled the quit rate. PMID- 26801403 TI - Post-weaning blood transcriptomic differences between Yorkshire pigs divergently selected for residual feed intake. AB - BACKGROUND: Improving feed efficiency (FE) of pigs by genetic selection is of economic and environmental significance. An increasingly accepted measure of feed efficiency is residual feed intake (RFI). Currently, the molecular mechanisms underlying RFI are largely unknown. Additionally, to incorporate RFI into animal breeding programs, feed intake must be recorded on individual pigs, which is costly and time-consuming. Thus, convenient and predictive biomarkers for RFI that can be measured at an early age are greatly desired. In this study, we aimed to explore whether differences exist in the global gene expression profiles of peripheral blood of 35 to 42 day-old pigs with extremely low (more efficient) and high RFI (less efficient) values from two lines that were divergently selected for RFI during the grow-finish phase, to use such information to explore the potential molecular basis of RFI differences, and to initiate development of predictive biomarkers for RFI. RESULTS: We identified 1972 differentially expressed genes (DEGs) (q <= 0.15) between the low (n = 15) and high (n = 16) RFI groups of animals by using RNA sequencing technology. We validated 24 of 37 selected DEGs by reverse transcription-quantitative PCR (RT-qPCR) in a joint analysis of 24 (12 per line) of the 31 samples already used for RNA-seq plus 24 (12 per line) novel samples from the same contemporary group of pigs. Using an analysis of the 24 novel samples alone, only nine of the 37 selected DEGs were validated. Genes involved in small molecule biosynthetic process, antigen processing and presentation of peptide antigen via major histocompatibility complex (MHC) class I, and steroid biosynthetic process were overrepresented among DEGs that had higher expression in the low versus high RFI animals. Genes known to function in the proteasome complex or mitochondrion were also significantly enriched among genes with higher expression in the low versus high RFI animals. Alternatively, genes involved in signal transduction, bone mineralization and regulation of phosphorylation were overrepresented among DEGs with lower expression in the low versus high RFI animals. The DEGs significantly overlapped with genes associated with disease, including hyperphagia, eating disorders and mitochondrial diseases (q < 1E-05). A weighted gene co-expression network analysis (WGCNA) identified four co-expression modules that were differentially expressed between the low and high RFI groups. Genes involved in lipid metabolism, regulation of bone mineralization, cellular immunity and response to stimulus were overrepresented within the two modules that were most significantly differentially expressed between the low and high RFI groups. We also found five of the DEGs and one of the co-expression modules were significantly associated with the RFI phenotype of individual animals (q < 0.05). CONCLUSIONS: The post-weaning blood transcriptome was clearly different between the low and high RFI groups. The identified DEGs suggested potential differences in mitochondrial and proteasomal activities, small molecule biosynthetic process, and signal transduction between the two RFI groups and provided potential new insights into the molecular basis of RFI in pigs, although the observed relationship between the post-weaning blood gene expression and RFI phenotype measured during the grow-finish phase was not strong. DEGs and representative genes in co-expression modules that were associated with RFI phenotype provide a preliminary list for developing predictive biomarkers for RFI in pigs. PMID- 26801405 TI - Increased Lipoprotein-associated phospholipase A2 activity portends an increased risk of resistant hypertension. AB - BACKGROUND: To investigate the relationship between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and incidence of resistant hypertension (RH). METHODS: This was a cross-sectional research. In essential, it was an observational design and collecting data on a population at a single point in time to evaluate the associations of studied variables. Totally 208 patients with arterial hypertension were enrolled. Baseline characteristics were collected and fasting venous blood were drawn for plasma Lp-PLA2 activity assessment. Twenty four hour ambulatory blood pressure ambulatory (ABPM) was performed to diagnose RH. Initially, based on ABPM examination, all participants were divided into two groups, namely RH group and without RH group. And thereafter, in order to evaluate the effects of Lp-PLA2 activity on blood pressure, all participants were divided into low (< 225 nm/min/ml) and high (>= 225 nm/min/ml) Lp-PLA2 activity groups based on the cut-off value of Lp-PLA2 activity. Comparisons were conducted between groups. RESULTS: Forty two patients were diagnosed as RH. Compared to patients without RH, patients with RH were more elderly, had more males, smokers, longer duration of hypertension, higher plasma C-reactive protein (CRP) level and Lp-PLA2 activity (P < 0.05 for all comparisons). More RH patients treated with calcium channel blocker and diuretic, while less treated with angiotensin converting enzyme inhibitor, angiotensin receptor blocker and statins (P < 0.05 for all comparisons). Compared to low Lp-PLA2 group, the rate of RH was significantly higher in high Lp-PLA2 group (26.7 % versus 6.1 %, P < 0.05). Multivariate regression analysis revealed that after adjusted for age, gender, smoking, body mass index, hypertension duration, CRP, and anti-hypertensive drugs, association between Lp-PLA2 activity and RH remained significant, with odds ratio (OD) of 2.02 (95 % confidence interval, CI 1.85-2.06, P < 0.05). Nonetheless, the association was attenuated when further adjusted for statins, with OR of 1.81 (95 % CI 1.74-1.93, P < 0.05). CONCLUSION: Increased plasma Lp PLA2 activity portends increased risk of RH, and statins may be beneficial to reduce incidence of RH in subjects with increased plasma Lp-PLA2 activity. PMID- 26801404 TI - Prenatal screening for psychosocial risks in a high risk-population in Peru using the KINDEX interview. AB - BACKGROUND: Prenatal stress and other prenatal risk factors (e.g. intimate partner violence) have a negative impact on mother's health, fetal development as well as enduring adverse effects on the neuro-cognitive, behavioral and physical health of the child. Mothers of low socio-economic status and especially those living in crime-ridden areas are even more exposed to a host of risk factors. Societies of extreme violence, poverty and inequalities, often present difficulties to provide adequate mental health care to the most needed populations. The KINDEX, a brief standardized instrument that assesses 11 different risk factors was used by midwives to identify pregnant women at-risk, in a suburban area with one of the highest levels of domestic violence in Lima. The instrument was designed to be used by medical staff to identify high-risk child-bearing women and, based on the results, to refer them to the adequate psychological or social support providers. The aim of this study is to assess the feasibility of psychosocial screening using the KINDEX in a Latin American Country for the first time, and to explore the relationship of the KINDEX with thee major risk areas, maternal psychopathology, perceived stress and traumatic experiences. METHODS: The study was conducted in cooperation with the gynecological department of a general hospital in a suburban area of Lima. Nine midwives conducted interviews using the KINDEX of ninety-five pregnant women attending the gynecological unit of the hospital. From these, forty pregnant women were re-interviewed by a clinical psychologist using established instruments in order to assess the feasibility of the prenatal assessment in public health settings and the relationship of the KINDEX with maternal perceived stress, psychopathology symptoms and trauma load during pregnancy. RESULTS: We found high rates of risk factors in the examined pregnant women comparable with those found in the general population. Significant correlations were found between the KINDEX sum score and the three risks areas, stress, psychopathology and trauma load as assessed in the Clinical Expert interviews. The different risks assessed by the KINDEX are related to higher levels of stress, psychopathology and trauma load, depending on the risk. CONCLUSIONS: The relationship between past adverse experience and current stressors with perceived maternal stress, psychopathology symptoms and traumatic experiences confirm the importance of prenatal assessment for psychosocial risks. The use of KINDEX by midwives providing obstetrical care to pregnant women in urban Peru is feasible and can be used to identify high-risk women and refer them to the adequate mental health or social services for necessary attention and support. Early interventions are essential to mitigating the adverse effects of maternal stress, trauma and psychopathology on the fetus and child. PMID- 26801407 TI - Characteristics of asymptomatic Plasmodium spp. parasitaemia in Kwahu-Mpraeso, a malaria endemic mountainous district in Ghana, West Africa. AB - BACKGROUND: Malaria control efforts in Ghana have reduced the countrywide average malaria prevalence from 71% in 2000 to about 51% in 2012; however, its main focus is on symptomatic malaria. If further progress is to be made, parasite reservoirs in asymptomatic carriers need to be moved into focus. This study profiles asymptomatic Plasmodium spp. parasitaemia amongst residents of mountainous Kwahu Mpraeso in the Eastern region of Ghana. METHODS: A cross-sectional study of 360 residents was carried out from October to December 2013. This included recording demographics, malaria testing of asymptomatic residents, and gathering of their malaria history. Assessment of malaria transmission was done with molecular identification of vectors, determination of sporozoite rate, insecticide resistance status and biting pattern. Univariate and multivariate analysis were used to establish risk determinants. RESULTS: In Mpraeso, in the Kwahu highland of Eastern Region, children were at higher risk of asymptomatic parasitaemia, thereby contributing to the parasite reservoir and hence sustained malaria transmission. As well, findings suggested Hb AC genotype influenced susceptibility to asymptomatic malaria with 8.03-fold increase in odds (univariate) and 11.92-fold higher odds (multivariate) than the normal Hb AA. The mosquito vector predominant in the area was Anopheles gambiae sensu stricto of the homozygous pyrethroid resistant form (RR); with biting mainly occurring indoors. CONCLUSION: For an effective malaria control in this area, interventions should be formulated and implemented to target asymptomatic parasite reservoirs; especially in children and people with Hb AC. The dominant vector species An. gambiae s.s. and its feeding patterns of biting indoors should also be considered. PMID- 26801408 TI - Capturing judgement strategies in risk assessments with improved quality of clinical information: How nurses' strategies differ from the ecological model. AB - BACKGROUND: Nurses' risk assessments of patients at risk of deterioration are sometimes suboptimal. Advances in clinical simulation mean higher quality information can be used as an alternative to traditional paper-based approaches as a means of improving judgement. This paper tests the hypothesis that nurses' judgement strategies and policies change as the quality of information used by nurses in simulation changes. METHODS: Sixty-three student nurses and 34 experienced viewed 25 paper-case based and 25 clinically simulated scenarios, derived from real cases, and judged whether the (simulated) patient was at 'risk' of acute deterioration. Criteria of judgement "correctness" came from the same real cases. Information relative weights were calculated to examine judgement policies of individual nurses. Group comparisons of nurses and students under both paper and clinical simulation conditions were undertaken using non parametric statistical tests. Judgment policies were also compared to the ecological statistical model. Cumulative relative weights were calculated to assess how much information nurses used when making judgements. Receiver operating characteristic (ROC) curves were generated to examine predictive accuracy amongst the nurses. RESULTS: There were significant variations between nurses' judgement policies and those optimal policies determined by the ecological model. Nurses significantly underused the cues of consciousness level, respiration rate, and systolic blood pressure than the ecological model requires. However, in clinical simulations, they tended to make appropriate use of heart rate, with non-significant difference in the relative weights of heart rate between clinical simulations and the ecological model. Experienced nurses paid substantially more attention to respiration rate in the simulated setting compared to paper cases, while students maintained a similar attentive level to this cue. This led to a non-significant difference in relative weights of respiration rate between experienced nurses and students. CONCLUSIONS: Improving the quality of information by clinical simulations significantly impacted on nurses' judgement policies of risk assessments. Nurses' judgement strategies also varied with the increased years of experience. Such variations in processing clinical information may contribute to nurses' suboptimal judgements in clinical practice. Constructing predictive models of common judgement situations, and increasing nurses' awareness of information weightings in such models may help improve judgements made by nurses. PMID- 26801406 TI - Cognitive remission: a novel objective for the treatment of major depression? AB - BACKGROUND: Cognitive dysfunction in major depressive disorder (MDD) encompasses several domains, including but not limited to executive function, verbal memory, and attention. Furthermore, cognitive dysfunction is a frequent residual manifestation in depression and may persist during the remitted phase. Cognitive deficits may also impede functional recovery, including workforce performance, in patients with MDD. The overarching aims of this opinion article are to critically evaluate the effects of available antidepressants as well as novel therapeutic targets on neurocognitive dysfunction in MDD. DISCUSSION: Conventional antidepressant drugs mitigate cognitive dysfunction in some people with MDD. However, a significant proportion of MDD patients continue to experience significant cognitive impairment. Two multicenter randomized controlled trials (RCTs) reported that vortioxetine, a multimodal antidepressant, has significant precognitive effects in MDD unrelated to mood improvement. Lisdexamfetamine dimesylate was shown to alleviate executive dysfunction in an RCT of adults after full or partial remission of MDD. Preliminary evidence also indicates that erythropoietin may alleviate cognitive dysfunction in MDD. Several other novel agents may be repurposed as cognitive enhancers for MDD treatment, including minocycline, insulin, antidiabetic agents, angiotensin-converting enzyme inhibitors, S-adenosyl methionine, acetyl-L-carnitine, alpha lipoic acid, omega-3 fatty acids, melatonin, modafinil, galantamine, scopolamine, N-acetylcysteine, curcumin, statins, and coenzyme Q10. The management of cognitive dysfunction remains an unmet need in the treatment of MDD. However, it is hoped that the development of novel therapeutic targets will contribute to 'cognitive remission', which may aid functional recovery in MDD. PMID- 26801410 TI - Information requirements of young women with breast cancer treated with mastectomy or breast conserving surgery: A systematic review. AB - OBJECTIVES: Young women with breast cancer have poorer prognosis, greater lifetime risk of local recurrence, contralateral recurrence, and distant disease, regardless of surgery received. Here we systematically review published evidence relating to the information requirements and preferences of young women diagnosed with early-stage breast cancer offered a choice between mastectomy and Breast Conservation Surgery (BCS). Findings will inform the development of a surgical decision aid for young women. METHODS: Eight databases were searched to identify research examining information requirements of young women facing breast oncological surgery treatment decisions (MESH headings). Twelve studies met the inclusion criteria. Data were extracted and summarised in a narrative synthesis. RESULTS: Findings indicate that young women prefer greater and more detailed information regarding treatment side effects, sexuality, and body image. Younger age of diagnosis leads to an increased risk perception of developing a second breast cancer. Young women's choices are influenced by factors associated with family and career. Information is required in a continuum throughout the treatment experience and not only at diagnosis when treatment decisions are made. Young women show differing levels of participation preferences. CONCLUSION: Young women find decision-making challenging when the characteristics of diagnosis provide a surgical choice between mastectomy and breast conservation surgery. Efforts should be made to provide information regarding sexuality, body image, reconstruction, fertility and likelihood of familial predisposition. Further research is needed to identify the specific level and information requirements of this young-onset group. The low number of studies indicate a need to design studies targeting specifically this age group of breast cancer patients. PMID- 26801409 TI - Lung cancer risk test trial: study design, participant baseline characteristics, bronchoscopy safety, and establishment of a biospecimen repository. AB - BACKGROUND: The Lung Cancer Risk Test (LCRT) trial is a prospective cohort study comparing lung cancer incidence among persons with a positive or negative value for the LCRT, a 15 gene test measured in normal bronchial epithelial cells (NBEC). The purpose of this article is to describe the study design, primary endpoint, and safety; baseline characteristics of enrolled individuals; and establishment of a bio-specimen repository. METHODS/DESIGN: Eligible participants were aged 50-90 years, current or former smokers with 20 pack-years or more cigarette smoking history, free of lung cancer, and willing to undergo bronchoscopic brush biopsy for NBEC sample collection. NBEC, peripheral blood samples, baseline CT, and medical and demographic data were collected from each subject. DISCUSSION: Over a two-year span (2010-2012), 403 subjects were enrolled at 12 sites. At baseline 384 subjects remained in study and mean age and smoking history were 62.9 years and 50.4 pack-years respectively, with 34% current smokers. Obstructive lung disease (FEV1/FVC <0.7) was present in 157 (54%). No severe adverse events were associated with bronchoscopic brushing. An NBEC and matched peripheral blood bio-specimen repository was established. The demographic composition of the enrolled group is representative of the population for which the LCRT is intended. Specifically, based on baseline population characteristics we expect lung cancer incidence in this cohort to be representative of the population eligible for low-dose Computed Tomography (LDCT) lung cancer screening. Collection of NBEC by bronchial brush biopsy/bronchoscopy was safe and well-tolerated in this population. These findings support the feasibility of testing LCRT clinical utility in this prospective study. If validated, the LCRT has the potential to significantly narrow the population of individuals requiring annual low-dose helical CT screening for early detection of lung cancer and delay the onset of screening for individuals with results indicating low lung cancer risk. For these individuals, the small risk incurred by undergoing once in a lifetime bronchoscopic sample collection for LCRT may be offset by a reduction in their CT-related risks. The LCRT biospecimen repository will enable additional studies of genetic basis for COPD and/or lung cancer risk. TRIAL REGISTRATION: The LCRT Study, NCT 01130285, was registered with Clinicaltrials.gov on May 24, 2010. PMID- 26801411 TI - A nationwide pathology study on surgical margins and excision volumes after breast-conserving surgery: There is still much to be gained. AB - AIM OF THE STUDY: The current study aims to assess margin status in relation to amount of healthy breast tissue resected in breast-conserving surgery (BCS) on a nationwide scale. METHODS: Using PALGA (a nationwide network and registry of histology and cytopathology in the Netherlands), all patients who underwent BCS for primary invasive carcinoma in 2012-13 were selected (10,058 excerpts). 9276 pathology excerpts were analyzed for a range of criteria including oncological margin status and distance to closest margin, specimen weight/volume, greatest tumor diameter, and with or without localization method. Calculated resection ratios (CRR) were assessed to determine excess healthy breast tissue resection. RESULTS: Margins for invasive carcinoma and in situ carcinoma combined were tumor involved in 498 (5.4%) and focally involved in 1021 cases (11.0%) of cases. Unsatisfactory resections including (focally) involved margins and margins <= 1 mm were reported in 33.8% of patients. The median lumpectomy volume was 46 cc (range 1-807 cc; SD 49.18) and median CRR 2.32 (range 0.10-104.17; SD 3.23), indicating the excision of 2.3 the optimal resection volume. CONCLUSION: The unacceptable rate of tumor-involved margins as well as margins <= 1 mm in one third of all patients is also achieved at the expense of healthy breast tissue resection, which may carry the drawback of high rates of cosmetic failure. These data clearly suggest the need for improvement in current breast conserving surgical procedures to decrease tumor-involved margin rates while reducing the amount of healthy breast tissue resected. PMID- 26801454 TI - An Empirical Comparison of Variable Standardization Methods in Cluster Analysis. AB - It is common practice in marketing research to standardize the columns (to mean zero and unit standard deviation) of a persons by variables data matrix, prior to clustering the entities corresponding to the rows of that matrix. This practice is often followed even when the columns are all expressed in similar units, such as ratings on a 7-point, equal interval scale. This study examines six different ways of standardizing matrix columns and compares them with the null case of no column standardization. The analysis is replicated for ten large-scale data sets, comprising derived importances of conjoint-based attributes. Our findings indicate that the prevailing column standardization practice may be problematic for some kinds of data that marketing researchers use for segmentation. However, we also find that in the background data profiling step, results are reasonably robust to column standardization method. PMID- 26801412 TI - Risk factors for brain metastasis as a first site of disease recurrence in patients with HER2 positive early stage breast cancer treated with adjuvant trastuzumab. AB - PURPOSE: The aim of this study was to determine risk factors for brain metastasis as the first site of disease recurrence in patients with HER2-positive early stage breast cancer (EBC) who received adjuvant trastuzumab. METHODS: Medical records of 588 female patients who received 52-week adjuvant trastuzumab from 14 centers were evaluated. Cumulative incidence functions for brain metastasis as the first site of disease recurrence and the effect of covariates on brain metastasis were evaluated in a competing risk analysis and competing risks regression, respectively. RESULTS: Median follow-up time was 36 months. Cumulative incidence of brain metastasis at 12 months and 24 months was 0.6% and 2%, respectively. HER2-enriched subtype (ER- and PR-) tumor (p = 0.001, RR: 3.4, 95% CI: 1.33-8.71) and stage 3 disease (p = 0.0032, RR: 9.39, 95% CI: 1.33-8.71) were significant risk factors for development of brain metastasis as the first site of recurrence. CONCLUSIONS: In patients with HER2 positive EBC who received adjuvant trastuzumab, HER2-enriched subtype (ER- and PR-) tumor and stage 3 disease were associated with increased risk of brain metastasis as the first site of disease recurrence. PMID- 26801413 TI - The use of granulocyte colony stimulating factor (G-CSF) and management of chemotherapy delivery during adjuvant treatment for early-stage breast cancer- further observations from the IMPACT solid study. AB - OBJECTIVE: To investigate the use and impact of granulocyte colony-stimulating factors (G-CSF) on chemotherapy delivery and neutropenia management in breast cancer in a clinical practice setting. METHODS: IMPACT Solid was an international, prospective observational study in patients with a physician assessed febrile neutropenia (FN) risk of >=20%. This analysis focused on stages I-III breast cancer patients who received a standard chemotherapy regimen for which the FN risk was published. Chemotherapy delivery and neutropenia-related outcomes were reported according to the FN risk of the regimen and intent of G CSF use. RESULTS: 690 patients received a standard chemotherapy regimen; 483 received the textbook dose/schedule with a majority of these regimens (84%) having a FN risk >=10%. Patients receiving a regimen with a FN risk >=10% were younger with better performance status than those receiving a regimen with a FN risk <10%. Patients who received higher-risk regimens were more likely to receive G-CSF primary prophylaxis (48% vs 22%), complete their planned chemotherapy (97% vs 88%) and achieve relative dose intensity >=85% (93% vs 86%) than those receiving lower-risk regimens. Most first FN events (56%) occurred in cycles not supported with G-CSF primary prophylaxis. CONCLUSION: Physicians generally recommend standard adjuvant chemotherapy regimens and were more likely to follow G-CSF guidelines for younger, good performance status patients in the curative setting, and often modify standard regimens in more compromised patients. However, G-CSF support is not optimal, indicated by G-CSF primary prophylaxis use in <50% of high-risk patients and observation of FN without G-CSF support. PMID- 26801455 TI - Using Log-Linear Models for Longitudinal Data to Test Alternative Explanations for Stage-Like Phenomena: An Example from Research on Adolescent Substance Use. AB - We show how log-linear models for multi-wave longitudinal data can be used to test hypotheses relating to stage-like relationships between variables. To illustrate our approach, we use an example from research on adolescent cigarette and marijuana experimentation. Previous research has documented that most adolescents experiment with substances in a stage-like sequence: first cigarettes and then marijuana. Several hypotheses have been suggested as potential explanations for this stage-like phenomenon. We show that traditional two-wave analyses give results that are difficult to interpret and that our multiple-wave analyses allow the testing of several theoretically interesting hypotheses. We also illustrate that log-linear models may be useful for testing hypotheses about stage-like phenomena in many other areas of psychological research. We suggest how several other techniques have the potential to be used as a multivariate analogue to the log-linear approach. PMID- 26801456 TI - Maximizing the Usefulness of Data Obtained with Planned Missing Value Patterns: An Application of Maximum Likelihood Procedures. AB - Researchers often face a dilemma: Should they collect little data and emphasize quality, or much data at the expense of quality? The utility of the 3-form design coupled with maximum likelihood methods for estimation of missing values was evaluated. In 3-form design surveys, four sets of items. X, A, B, and C are administered: Each third of the subjects receives X and one combination of two other item sets - AB, BC, or AC. Variances and covariances were estimated with pairwise deletion, mean replacement, single imputation, multiple imputation, raw data maximum likelihood, multiple-group covariance structure modeling, and Expectation-Maximization (EM) algorithm estimation. The simulation demonstrated that maximum likelihood estimation and multiple imputation methods produce the most efficient and least biased estimates of variances and covariances for normally distributed and slightly skewed data when data are missing completely at random (MCAR). Pairwise deletion provided equally unbiased estimates but was less efficient than ML procedures. Further simulation results demonstrated that nun maximum likelihood methods break down when data are not missing completely at random. Application of these methods with empirical drug use data resulted in similar covariance matrices for pairwise and EM estimation, however, ML estimation produced better and more efficient regression estimates. Maximum likelihood estimation or multiple imputation procedures. which are now becoming more readily available, are always recommended. In order to maximize the efficiency of the ML parameter estimates, it is recommended that scale items be split across forms rather than being left intact within forms. PMID- 26801457 TI - Correlation as Probability of Common Descent. AB - We highlight one interpretation of Pearson's r (largely unknown to behavioral scientists), inspired by the genetic measurement of inbreeding. The coefficient of inbreeding, defined as the probability that two paired alleles originate from common descent, equals the correlation between the uniting gametes. We specify the statistical conditions under which r can be interpreted as probability of identity by descent and explore the possibility of generalizing that meaning of correlation beyond the inbreeding context. Extensions to the framework of agreement between judges and to that of sequential dependencies are considered. Viewing correlation as probability is heuristically promising. We examine the implications of this approach in the case of three types of bivariate distributions and discuss potential insights and risks. PMID- 26801458 TI - Path Analysis with Composite Variables. AB - Six methods for fitting path models with weighted composites of variables replacing latent variables (of which five are easily implemented with conventional computer software) are introduced and related to "soft modelling" by Partial Least Squares. Criteria for comparing their performance are devised. and some evaluative remarks are offered. PMID- 26801460 TI - Correction. PMID- 26801459 TI - Social, demographic and healthcare factors associated with stage at diagnosis of cervical cancer: cross-sectional study in a tertiary hospital in Northern Uganda. AB - OBJECTIVE: To examine patient and primary healthcare factors and stage at diagnosis in women with cervical cancer in Northern Uganda with the intention to identify factors that are associated with advanced stages in order to inform policies to improve survival from cervical cancer in low income and middle income countries. DESIGN: Cross-sectional hospital-based study. SETTING: Tertiary, not for-profit private hospital in postconflict region. PARTICIPANTS: Consecutive tissue-diagnosed symptomatic patients with cervical attending care. Of 166 patients, 149 were enrolled and analysed. PRIMARY OUTCOME: Cervical cancer stage at diagnosis. RESULTS: Most women were diagnosed at stages III (45%) or IV (21%). After controlling for age, marital status, educational attainment and number of biological children, there was evidence for association between advanced stage at diagnosis and pre-referral diagnosis of cancer by primary healthcare professionals (adjusted OR (AOR)=13.04:95% CI 3.59 to 47.3), and financial difficulties precluding prompt help seeking (AOR=5.5:95% CI 1.58 to 20.64). After adjusting for age, marital status and educational attainment, women with 5-9 biological children (AOR=0.27:95% CI 0.08 to 0.96) were less likely to be diagnosed with advanced stage (defined as stages III/IV) cancer. In this pilot study, there was no statistical evidence for associations between stage at diagnosis, and factors such as age at diagnosis and marital status. CONCLUSIONS: This study is a first attempt to understand the descriptive epidemiology of cervical cancer in rural Ugandan settings. Understanding individual patient factors, patients' behavioural characteristics and healthcare factors associated with advanced stage at diagnosis is essential for targeted effective public health interventions to promote prompt health seeking, diagnosis at early stage and improved survival from cervical cancer. PMID- 26801461 TI - Correction. PMID- 26801462 TI - Diagnostic accuracy of shear wave elastography for prediction of breast malignancy in patients with pathological nipple discharge. AB - OBJECTIVES: Pathological nipple discharge (PND) may indicate malignant breast lesions. As the role of shear wave elastography (SWE) in predicting these malignant lesions has not yet been evaluated, we aim to evaluate the diagnostic value of SWE for this condition. DESIGN: Prospective diagnostic accuracy study comparing a combination of qualitative and quantitative measurements of SWE (index test) to a ductoscopy and microdochectomy for histological diagnosis (reference test). SETTING: Fuzhou General Hospital of Nanjing military command. PARTICIPANTS: A total of 379 patients with PND were finally included from January, 2011 to March 2014, after we screened 1084 possible candidates. All participants were evaluated through SWE, with qualitative parameters generated by Virtual Touch tissue imaging (VTI) and quantitative parameters generated by Virtual Touch tissue quantification (VTQ). All the patients were consented to receive a ductoscopy and microdochectomy for histological diagnosis, and the results were set as a reference test. OUTCOME MEASURES: Sensitivity and specificity of the combined VTI and VTQ of the SWE for detection of malignancy in patients with PND. RESULTS: The 379 participants presented with 404 lesions. The results of pathological examination showed that 326 (80.7%) of the 404 lesions were benign and the other 78 (19.3%) were malignant. An area under the curve of elasticity score, VTQm and VTQc, were 0.872, 0.825 and 0.857, respectively, with the corresponding cut-off point as 2.50, 2.860 m/s and 3.015 m/s, respectively. After a combination of these measurements, the sensitivity, specificity, and positive and negative predictive value (PPV and NPV), were 89.7%, 72.1%, 43.5% and 96.7%, respectively. The sensitivity analysis showed 82% of the sensitivity and 96.8% of the specificity, in which patients with no pathological findings in ductoscopy were excluded. CONCLUSIONS: Ultrasonographic elastography is sensitive for patients with PND and could be used as a triage test before ductoscopy examination. Studies for further improvement of diagnostic sensitivity are warranted. PMID- 26801463 TI - Patient characteristics associated with risk of first hospital admission and readmission for acute exacerbation of chronic obstructive pulmonary disease (COPD) following primary care COPD diagnosis: a cohort study using linked electronic patient records. AB - OBJECTIVES: To investigate patient characteristics of an unselected primary care population associated with risk of first hospital admission and readmission for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). DESIGN: Retrospective open cohort using pseudonymised electronic primary care data linked to secondary care data. SETTING: Primary care; Lothian (population approximately 800,000), Scotland. PARTICIPANTS: Data from 7002 patients from 72 general practices with a COPD diagnosis date between 2000 and 2008 recorded in their primary care record. Patients were followed up until 2010, death or they left a participating practice. MAIN OUTCOME MEASURES: First and subsequent admissions for AECOPD (International Classification of Diseases (ICD) 10 codes J44.0, J44.1 in any diagnostic position) after COPD diagnosis in primary care. RESULTS: 1756 (25%) patients had at least 1 AECOPD admission; 794 (11%) had at least 1 readmission and the risk of readmission increased with each admission. Older age at diagnosis, more severe COPD, low body mass index (BMI), current smoking, increasing deprivation, COPD admissions and interventions for COPD prior to diagnosis in primary care, and comorbidities were associated with higher risk of first AECOPD admission in an adjusted Cox proportional hazards regression model. More severe COPD and COPD admission prior to primary care diagnosis were associated with increased risk of AECOPD readmission in an adjusted Prentice Williams-Peterson model. High BMI was associated with a lower risk of first AECOPD admission and readmission. CONCLUSIONS: Several patient characteristics were associated with first AECOPD admission in a primary care cohort of people with COPD but fewer were associated with readmission. Prompt diagnosis in primary care may reduce the risk of AECOPD admission and readmission. The study highlights the important role of primary care in preventing or delaying a first AECOPD admission. PMID- 26801464 TI - Missed opportunities to offer HIV tests to high-risk groups during general practitioners' STI-related consultations: an observational study. AB - OBJECTIVES: Prior research has shown that Dutch general practitioners (GPs) do not always offer HIV testing and the number of undiagnosed HIV patients remains high. We aimed to further investigate the frequency and reasons for (not) testing for HIV and the contribution of GPs to the diagnosis of HIV infections in the Netherlands. DESIGN: Observational study. SETTING: (1) Dutch primary care network of 42-45 sentinel practices where report forms during sexually transmitted infection (STI)-related consultations were routinely collected, 2008-2013. (2) Dutch observational cohort with medical data of HIV-positive patients in HIV care, 2008-2013. OUTCOME MEASURES: The proportion of STI-related consultations in patients from high-risk groups tested for HIV, with additional information requested from GPs on HIV testing preconsultation or postconsultation for whom HIV testing was indicated, but not performed. Next, information was collected on the profile of HIV-positive patients entering specialised HIV care following diagnosis by GPs. RESULTS: Initially, an HIV test was reported (360/907) in 40% of STI-related consultations in high-risk groups. Additionally, in 26% of consultations an HIV test had been performed in previous or follow-up consultations or at different STI-care facilities. The main reasons for not testing were perceived insignificant risk; 'too' recent risk according to GPs or the reluctance of patients. The initiative of the patient was a strong determinant for HIV testing. GPs diagnosed about one third of all newly found cases of HIV. Compared with STI clinics, HIV-positive patients diagnosed in general practice were more likely to be older, female, heterosexual male or sub Saharan African. CONCLUSIONS: In one-third of the STI-related consultations of persons from high-risk groups, no HIV test was performed in primary care, which is lower than previously reported. Risk-based testing has intrinsic limitations and implementation of new additional strategies in primary care is warranted. PMID- 26801465 TI - Incidence of multiple myeloma in Great Britain, Sweden, and Malmo, Sweden: the impact of differences in case ascertainment on observed incidence trends. AB - OBJECTIVES: The increased incidence of multiple myeloma (MM) across China and East Asia stimulated us to examine the current rates in Great Britain, where rates increased dramatically in the second half of the 20th century. However, rates have been stable and high during this period in Malmo, Sweden, where there is a keen interest in MM. We thus assessed recent changes in MM incidence in Great Britain, Sweden overall, and Malmo, Sweden, and examined how these changes might explain recent reports of increased MM incidence across Asia. DESIGN: Estimation of MM incidence for Great Britain, Sweden overall, and Malmo, Sweden. POPULATIONS: MM incidence data for Great Britain (1975-2009) were obtained from Cancer Research UK and for Sweden (1970-2009) from the Swedish Cancer Registry. MM incidence data from Malmo, Sweden, were available from 1950 to 2012. MAIN OUTCOME MEASURES: Age-specific incidence of MM in Great Britain, Sweden overall, and Malmo, Sweden. RESULTS: MM incidence in Great Britain, Sweden overall, and Malmo increased progressively with age, even among the oldest group. The MM age adjusted incidence (European standard population) increased by 69% from 1975-1979 to 2005-2009 in Great Britain, from 3.2/100,000 to 5.4/100,000. The largest increases occurred among those 70-79 years of age, for whom rates increased from 17.9/100,000 to 33.6/100,000; reflecting an increase of 69%. During this same period, the age-adjusted incidence (European stand population) in Sweden overall remained stable, at approximately 4.7/100,000. CONCLUSIONS: MM age-specific incidence is now similar in Great Britain, Sweden overall, and Malmo. We believe this is a result of improvements in case ascertainment in Great Britain, particularly among the elderly. Similar changes can be predicted to occur across Asia as improved access to healthcare contributes to better diagnosis of MM. PMID- 26801466 TI - Maternal death audit in Rwanda 2009-2013: a nationwide facility-based retrospective cohort study. AB - OBJECTIVE: Presenting the results of 5 years of implementing health facility based maternal death audits in Rwanda, showing maternal death classification, identification of substandard (care) factors that have contributed to death, and conclusive recommendations for quality improvements in maternal and obstetric care. DESIGN: Nationwide facility-based retrospective cohort study. SETTINGS: All cases of maternal death audited by district hospital-based audit teams between January 2009 and December 2013 were reviewed. Maternal deaths that were not subjected to a local audit are not part of the cohort. POPULATION: 987 audited cases of maternal death. MAIN OUTCOME MEASURES: Characteristics of deceased women, timing of onset of complications, place of death, parity, gravida, antenatal clinic attendance, reported cause of death, service factors and individual factors identified by committees as having contributed to death, and recommendations made by audit teams. RESULTS: 987 cases were audited, representing 93.1% of all maternal deaths reported through the national health management information system over the 5-year period. Almost 3 quarters of the deaths (71.6%) occurred at district hospitals. In 44.9% of these cases, death occurred in the post-partum period. Seventy per cent were due to direct causes, with post-partum haemorrhage as the leading cause (22.7%), followed by obstructed labour (12.3%). Indirect causes accounted for 25.7% of maternal deaths, with malaria as the leading cause (7.5%). Health system failures were identified as the main responsible factor for the majority of cases (61.0%); in 30.3% of the cases, the main factor was patient or community related. CONCLUSIONS: The facility-based maternal death audit approach has helped hospital teams to identify direct and indirect causes of death, and their contributing factors, and to make recommendations for actions that would reduce the risk of reoccurrence. Rwanda can complement maternal death audits with other strategies, in particular confidential enquiries and near-miss audits, so as to inform corrective measures. PMID- 26801467 TI - Pregnancy hypertensive disease and risk of dementia and cardiovascular disease in women aged 65 years or older: a cohort study. AB - OBJECTIVE: The primary aim was to study pregnancy hypertensive disease and subsequent risk of dementia. The second aim was to study if the increased risks of cardiovascular disease (CVD) and stroke after pregnancy hypertensive disease persist in an elderly population. DESIGN: Cohort study. SETTING: Sweden. POPULATION OR SAMPLE: 3232 women 65 years or older (mean 71 years) at inclusion. METHODS: Cox proportional hazards regression analyses were used to calculate risks of dementia, CVD and/or stroke for women exposed to pregnancy hypertensive disease. Exposure data were collected from an interview at inclusion during the years 1998-2002. Outcome data were collected from the National Patient Register and Cause of Death Register from the year of inclusion until the end of 2010. Age at inclusion was set as a time-dependent variable, and adjustments were made for body mass index, education and smoking. MAIN OUTCOME MEASURES: Dementia, CVD, stroke. RESULTS: During the years of follow-up, 7.6% of the women exposed to pregnancy hypertensive disease received a diagnosis of dementia, compared with 7.4% among unexposed women (HR 1.19; 95% CI 0.79 to 1.73). The corresponding rates for CVD were 22.9% for exposed women and 19.0% for unexposed women (HR 1.29; 95% CI 1.02 to 1.61), and for stroke 13.4% for exposed women and 10.7% for unexposed women (HR 1.36; 95% CI 1.00 to 1.81). CONCLUSIONS: There was no increased risk of dementia after self-reported pregnancy hypertensive disease in our cohort. We found that the previously reported increased risk of CVD and stroke after pregnancy hypertensive disease persists in an older population. PMID- 26801468 TI - Tablet computers for implementing NICE antenatal mental health guidelines: protocol of a feasibility study. AB - INTRODUCTION: Depression is one of the most common mental health disorders that may affect women during pregnancy. The prompt identification of this disorder, and the provision of treatment, may help to reduce the likelihood of post-partum depression, prevent severe forms of the disease, and reduce its intergenerational impact. Despite women's repeated encounters with health services throughout their antenatal care, depression often goes undiagnosed. This is one area where mobile health could prove useful. We will assess the feasibility of using tablets to incorporate depression screening into antenatal pathways. We will also assess if survey layout could affect the quality of the data collected through these devices. METHODS AND ANALYSIS: We will test the feasibility of using iPad Airs for the administration of the Whooley questions and the Edinburgh Postnatal Depression Scale (EPDS) to pregnant women attending antenatal clinics in England. We will assess the impact of survey layout on the quality of the responses given to these screening scales using a parallel, randomised controlled study design. We will calculate the positive predictive value, the negative predictive value and the false omission rate of the Whooley questions in comparison with the EPDS. We will calculate differences in data equivalence, time needed to complete the surveys, break-off rates, data completeness and requests for help between the 2 experimental groups: using all questions in one screen and navigation by vertical scrolling, or a single question per screen and navigation by multiple pages. ETHICS AND DISSEMINATION: This study has been approved by the National Research Ethics Service Committee South East Coast--Surrey. Our findings will be disseminated through academic peer-reviewed publications, conferences and discussion with peers. PMID- 26801469 TI - Bias in dissemination of clinical research findings: structured OPEN framework of what, who and why, based on literature review and expert consensus. AB - OBJECTIVE: The aim of this study is to review highly cited articles that focus on non-publication of studies, and to develop a consistent and comprehensive approach to defining (non-) dissemination of research findings. SETTING: We performed a scoping review of definitions of the term 'publication bias' in highly cited publications. PARTICIPANTS: Ideas and experiences of a core group of authors were collected in a draft document, which was complemented by the findings from our literature search. INTERVENTIONS: The draft document including findings from the literature search was circulated to an international group of experts and revised until no additional ideas emerged and consensus was reached. PRIMARY OUTCOMES: We propose a new approach to the comprehensive conceptualisation of (non-) dissemination of research. SECONDARY OUTCOMES: Our 'What, Who and Why?' approach includes issues that need to be considered when disseminating research findings (What?), the different players who should assume responsibility during the various stages of conducting a clinical trial and disseminating clinical trial documents (Who?), and motivations that might lead the various players to disseminate findings selectively, thereby introducing bias in the dissemination process (Why?). CONCLUSIONS: Our comprehensive framework of (non-) dissemination of research findings, based on the results of a scoping literature search and expert consensus will facilitate the development of future policies and guidelines regarding the multifaceted issue of selective publication, historically referred to as 'publication bias'. PMID- 26801470 TI - Theory-driven group-based complex intervention to support self-management of osteoarthritis and low back pain in primary care physiotherapy: protocol for a cluster randomised controlled feasibility trial (SOLAS). AB - INTRODUCTION: International clinical guidelines consistently endorse the promotion of self-management (SM), including physical activity for patients with chronic low back pain (CLBP) and osteoarthritis (OA). Patients frequently receive individual treatment and advice to self-manage from physiotherapists in primary care, but the successful implementation of a clinical and cost-effective group SM programme is a key priority for health service managers in Ireland to maximise long-term outcomes and efficient use of limited and costly resources. METHODS/ANALYSIS: This protocol describes an assessor-blinded cluster randomised controlled feasibility trial of a group-based education and exercise intervention underpinned by self-determination theory designed to support an increase in SM behaviour in patients with CLBP and OA in primary care physiotherapy. The primary care clinic will be the unit of randomisation (cluster), with each clinic randomised to 1 of 2 groups providing the Self-management of Osteoarthritis and Low back pain through Activity and Skills (SOLAS) intervention or usual individual physiotherapy. Patients are followed up at 6 weeks, 2 and 6 months. The primary outcomes are the (1) acceptability and demand of the intervention to patients and physiotherapists, (2) feasibility and optimal study design/procedures and sample size for a definitive trial. Secondary outcomes include exploratory analyses of: point estimates, 95% CIs, change scores and effect sizes in physical function, pain and disability outcomes; process of change in target SM behaviours and selected mediators; and the cost of the intervention to inform a definitive trial. ETHICS/DISSEMINATION: This feasibility trial protocol was approved by the UCD Human Research Ethics-Sciences Committee (LS-13-54 Currie-Hurley) and research access has been granted by the Health Services Executive Primary Care Research Committee in January 2014. The study findings will be disseminated to the research, clinical and health service communities through publication in peer-reviewed journals, presentation at national and international academic and clinical conferences. TRIAL REGISTRATION NUMBER: ISRCTN 49875385; Pre-results. PMID- 26801471 TI - Loss of Consciousness Is Related to White Matter Injury in Mild Traumatic Brain Injury. AB - To study the relation of loss of consciousness (LOC) to white matter integrity after mild traumatic brain injury (mTBI), we acquired diffusion tensor imaging (DTI) at 3 Tesla in 79 participants with mTBI and normal computed tomography (age 18 to 50 years) whom we imaged after a mean post-injury interval of 25.9 h (standard deviation = 12.3) and at 3 months. For comparison, 64 participants with orthopedic injury (OI) underwent DTI at similar intervals. Quantitative tractography was used to measure fractional anisotropy (FA) and mean diffusivity (MD) in the left and right uncinate fasciculus (UF), left and right inferior frontal occipital fasciculus (IFOF), and the genu of the corpus callosum. Generalized estimating equation models assessed the association between LOC and both MD and FA across time after mTBI and compared their DTI metrics with the OI group. LOC was significantly related to MD in UF and IFOF (p values ranged from p < 0.0001 to 0.0270) and to FA in left UF (p = 0.0104) and right UF (p = 0.0404). Between-group differences in MD were significant for left UF, left and right IFOF, and the genu of the corpus callosum on initial DTI, but not at 3 months post-injury, and these differences were specific to the mTBI subgroup with LOC. Groups did not differ in FA at either occasion. Early DTI may provide a biomarker for mTBI with LOC, even in patients whose consciousness recovers by arrival in the emergency department. MD better differentiates mTBI from OI than FA on early DTI, but this is specific to mTBI with LOC. DTI findings support a continuum of white matter injury in early mTBI. PMID- 26801472 TI - Evolution of male age-specific reproduction under differential risks and causes of death: males pay the cost of high female fitness. AB - Classic theories of ageing evolution predict that increased extrinsic mortality due to an environmental hazard selects for increased early reproduction, rapid ageing and short intrinsic lifespan. Conversely, emerging theory maintains that when ageing increases susceptibility to an environmental hazard, increased mortality due to this hazard can select against ageing in physiological condition and prolong intrinsic lifespan. However, evolution of slow ageing under high condition-dependent mortality is expected to result from reallocation of resources to different traits and such reallocation may be hampered by sex specific trade-offs. Because same life-history trait values often have different fitness consequences in males and females, sexually antagonistic selection can preserve genetic variance for lifespan and ageing. We previously showed that increased condition-dependent mortality caused by heat shock leads to evolution of long-life, decelerated late-life mortality in both sexes and increased female fecundity in the nematode, Caenorhabditis remanei. Here, we used these cryopreserved lines to show that males evolving under heat shock suffered from reduced early-life and net reproduction, while mortality rate had no effect. Our results suggest that heat-shock resistance and associated long-life trade-off with male, but not female, reproduction and therefore sexually antagonistic selection contributes to maintenance of genetic variation for lifespan and fitness in this population. PMID- 26801473 TI - The influence of metal-based biomaterials functionalized with sphingosine-1 phosphate on the cellular response and osteogenic differentaion potenial of human adipose derived mesenchymal stem cells in vitro. AB - In this study, stable, homogenous and thin titania dioxide coatings (TiO2) on stainless steel substrate doped with two dosages of bioactive sphingolipids S1P were fabricated using the sol-gel method. S1P belongs to a family of sphingolipids acting as important extracellular signaling molecules and chemoattractants. This study investigated the effect of TiO2, doped with S1P in two different dosages on cellular response as well as osteogenic differentiation potential of human adipose derived multipotent stromal stem cells (hASC). The authors have shown that S1P mediates hASCs morphology, proliferation activity and population doubling time in a dose-dependent manner. They have also demonstrated that functionalization of TiO2coating with a higher dosage of S1P, i.e. 80 ng/ml [(TiO2/S1P(CII)] activated both S1PR type 1 and type 2 on mRNA level. The results indicated an increase in secretion of BMP-2, Osteopontin and Osteocalcin by osteoblasts progenitor when cultured on [TiO2/S1P(CIIm)]. In addition, the authors observed the highest extracellular matrix mineralization as well as osteonodules formation by the osteoblasts precursors when cultured onto [TiO2/S1P(CIIm)]. PMID- 26801474 TI - Preparation of a small intestinal submucosa modified polypropylene hybrid mesh via a mussel-inspired polydopamine coating for pelvic reconstruction. AB - Pelvic organ prolapse (POP) is a serious health issue that affects many adult women. Surgical treatments for POP patients comprise a common strategy in which scaffold materials are used to reconstruct the prolapsed pelvic. However, the existing materials for pelvic reconstruction cannot meet clinical requirements in terms of biocompatibility, mechanics and immunological rejection. To address these concerns, polypropylene (PP) mesh was selected because of its strong mechanical properties. Small intestinal submucosa (SIS) was used to modify the PP mesh via a mussel-inspired polydopamine coating to enhance its biocompatibility. The scanning electron microscopy (SEM) and atomic force microscopy (AFM) results demonstrated that SIS was successfully conjugated on the surface of the PP mesh. Moreover, the cytotoxicity results indicated that the PP mesh and SIS-modified PP mesh were safe to use. Furthermore, in vivo tests demonstrated that the fibroplasia around the implanted site in the SIS-modified PP mesh group was significantly less than the fibroplasia around the PP mesh group. In addition, the immunohistochemistry staining results indicated that the expression of pro inflammatory macrophages (M1) was substantially lower and that the expression of pro-healing macrophages (M2) was higher in the SIS-modified PP mesh group. Furthermore, ELISA detection indicated that the expression of IL-1beta and IL-6 in the SIS-modified PP mesh group was reduced compared with the PP mesh group. These findings suggest that a SIS-modified polypropylene hybrid mesh via a mussel inspired polydopamine coating is a promising approach in pelvic reconstruction. PMID- 26801475 TI - Antigen-free bovine cancellous bone loaded with recombinant human bone morphogenetic protein-2 for the repair of tibial bone defects in goat model. AB - Antigen-free bovine cancellous bone has good performances of porous network structures and mechanics with antigen extracted. To develop a bioactive scaffold for enhancing bone repair and evaluate its biological property, rhBMP-2 loaded with antigen-free bovine cancellous bone was used to treat tibial bone defect. Twenty-four healthy adult goats were chosen to establish goat defects model and randomly divided into four groups. The goats were treated with rhBMP-2/antigen free bovine cancellous bone scaffolds (group A), autogenous cancellous bone graft (group B), porous tricalciumphosphate scaffolds (group C) and nothing (group D). Animals were evaluated with radiological and histological methods at 4, 8 and 12 weeks after surgery. The gray value of radiographs was used to evaluate the healing of the defects, which revealed that the group A had a better outcome of defect healing compared with group C at 4, 8 and 12 weeks, respectively (p < 0.05), while the difference between groups A and B was without significance at each time (p > 0.05). The newly formed bone area was calculated from histological sections, and the results indicated that the amount of new bone in group A increased significantly compared with that in group C (p < 0.05) but was similar to that in group B (p > 0.05) at 4, 8 and 12 weeks, respectively. In addition, the expression of collagen I and vascular endothelial growth factor by real-time polymerase chain reaction at 12 weeks in group A was significantly higher than that in group C (p = 0.034, p = 0.032, respectively), but no significant differences were found when compared with that in group B (p = 0.36, p = 0.54, respectively). At the same time, group C presented better results than group D on bone defects healing. Therefore, the composites of antigen-free bovine cancellous bone loaded with rhBMP-2 have a good osteoinductive activity and capacity to promote the repair of bone defects. PMID- 26801477 TI - Pre-clinical Experience with a Multi-Chordal Patch for Mitral Valve Repair. AB - Surgical repair of flail mitral valve leaflets with neochordoplasty has good outcomes, but implementing it in anterior and bi-leaflet leaflet repair is challenging. Placing and sizing individual neochordae is time consuming and error prone, with persistent localized flail if performed incorrectly. In this study, we report our pre-clinical experience with a novel multi-chordal patch for mitral valve repair. The device was designed based on human cadaver hearts, and laser cut from expanded polytetrafluoroethylene. The prototypes were tested in: (stage 1) ex vivo hearts with leaflet flail (N = 6), (stage 2) acute swine induced with flail (N = 6), and (stage 3) two chronic swine survived to 23 and 120 days (N = 2). A2 and P2 prolapse were successfully repaired with coaptation length restored to 8.1 +/- 2.2mm after posterior repair and to 10.2 +/- 1.3mm after anterior repair in ex vivo hearts. In vivo, trace regurgitation was seen after repair with excellent patch durability, healing, and endothelialization at euthanasia. A new device for easier mitral repair is reported, with good early pre-clinical outcomes. PMID- 26801478 TI - Prognostic Value of Tubulointerstitial Lesions, Urinary N-Acetyl-beta-d Glucosaminidase, and Urinary beta2-Microglobulin in Patients with Type 2 Diabetes and Biopsy-Proven Diabetic Nephropathy. AB - BACKGROUND AND OBJECTIVES: Some biomarkers of renal tubular injury are reported to be useful for predicting renal prognosis in the early stage of diabetic nephropathy (DN). Our study compared predictions of the renal prognosis by such biomarkers and by histologic tubulointerstitial damage. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 210 patients with type 2 diabetes and biopsy proven DN managed from 1985 to 2011, 149 patients with urinary N-acetyl-beta-d glucosaminidase (NAG) and urinary beta2-microglobulin (beta2-MG) data at the time of renal biopsy were enrolled. The primary outcome was a decline in eGFR of >=50% from baseline or commencement of dialysis for ESRD. RESULTS: The median follow-up period was 2.3 years (interquartile range, 1.1-5.3), and the primary outcome was noted in 94 patients. Mean eGFR was 46.3+/-23.2 ml/min per 1.73 m(2), and 132 patients (89%) had overt proteinuria at baseline. Cox proportional hazards analysis revealed that the association of urinary NAG and beta2-MG with the outcome was attenuated after adjustment for known promoters of progression (+1 SD for log NAG: hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 0.84 to 1.55; +1 SD for log beta2-MG: HR, 1.23; 95% CI, 0.94 to 1.62). In contrast, the interstitial fibrosis and tubular atrophy (IFTA) score was still significantly correlated with the outcome after adjustment for the same covariates (+1 for IFTA score: HR, 2.31; 95% CI, 1.56 to 3.43). Moreover, adding the IFTA score to a model containing known progression indicators improved prediction of the outcome (increase of concordance index by 0.02; 95% CI, 0.00 to 0.05; category-free net reclassification improvement by 0.54; 95% CI, 0.03 to 1.05; and relative integrated discrimination improvement by 0.07; 95% CI, -0.08 to 0.22). CONCLUSIONS: Adding urinary NAG and beta2-MG excretion to known promoters of progression did not improve prognostication, whereas adding the IFTA score did. The IFTA score may be superior to these tubulointerstitial markers for predicting the renal prognosis in advanced DN. PMID- 26801482 TI - Bullying, Physical Aggression, Gender-Atypicality, and Sexual Orientation in Samoan Males. AB - Bullying is characterized by the repeated attempts of a group or individual to gain social advantage by the use of relational, verbal, or physical aggression against a target, especially when there is a perceived or actual power imbalance (Espelage & Swearer, 2003). One consistent finding is that gay (i.e., androphilic) males report higher rates of victimization due to bullying in adolescence than their heterosexual (i.e., gynephilic) counterparts. Western data indicate that gender-atypical behavior, regardless of sexual orientation, is a key predictor of victimization due to bullying. Androphilic males generally display childhood gender-atypicality, including reduced levels of physical aggression, which may cause bullies to perceive them as "easy" targets. In order to test the associations between sexual orientation, childhood gender atypicality, and recalled victimization due to bullying, a sample of Samoan gynephilic men (n = 100) were compared to a group of Samoan transgender androphilic males (n = 103), known as fa'afafine. Although the fa'afafine reported far more childhood gender-atypicality, the two groups did not differ significantly on measures of physical aggression or their reported rates of victimization due to bullying. Additionally, greater physical aggression, not gender-atypicality, was the only significant predictor of being bullied in both men and fa'afafine. These results suggest that there is nothing inherent in sexual orientation or childhood gender-atypicality that would potentiate victimization from bullying. Instead, the cultural context in which a bully functions influences the extent to which these are "acceptable" reasons to target certain individuals. PMID- 26801479 TI - Serum Creatinine Back-Estimation in Cardiac Surgery Patients: Misclassification of AKI Using Existing Formulae and a Data-Driven Model. AB - BACKGROUND AND OBJECTIVES: A knowledge of baseline serum creatinine (bSCr) is mandatory for diagnosing and staging AKI. With often missing values, bSCr is estimated by back-calculation using several equations designed for the estimation of GFR, assuming a "true" GFR of 75 ml/min per 1.73 m(2). Using a data set from a large cardiac surgery cohort, we tested the appropriateness of such an approach and compared estimated and measured bSCr. Moreover, we designed a novel data driven model (estimated serum creatinine [eSCr]) for estimating bSCr. Finally, we analyzed the extent of AKI and mortality rate misclassifications. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data for 8024 patients (2833 women) in our cardiac surgery center were included from 1997 to 2008. Measured and estimated bSCr were plotted against age for men and women. Patients were classified to AKI stages defined by the Kidney Disease Improving Global Outcomes (KDIGO) group. Results were compared with data from another cardiac surgery center in Zurich, Switzerland. RESULTS: The Modification of Diet in Renal Disease and the Chronic Kidney Disease Epidemiology Collaboration formulae describe higher estimated bSCr values in younger patients, but lower values in older patients compared with the measured bSCr values in both centers. The Pittsburgh Linear Three Variables formula correctly describes the increasing bSCr with age, however, it underestimates the overall bSCr level, being in the range of the 25% quantile of the measured values. Our eSCr model estimated measured bSCr best. AKI stage 1 classification using all formulae, including our eSCr model, was incorrect in 53% 80% of patients in Vienna and in 74%-91% in Zurich; AKI severity (according to KDIGO stages) and also mortality were overestimated. Mortality rate was higher among patients falsely classified into higher KDIGO stages by estimated bSCr. CONCLUSIONS: bSCr values back-estimated using currently available eGFR formulae are inaccurate and cannot correctly classify AKI stages. Our model eSCr improves the prediction of AKI but to a still inadequate extent. PMID- 26801480 TI - Flow diverter treatment of posterior circulation aneurysms. A meta-analysis. AB - INTRODUCTION: Treatment of complex anterior circulation aneurysms with flow diverters (FDs) has become common practice in neurovascular centers. However, this treatment method for posterior circulation aneurysms (PCAs) still remains controversial. METHODS: Through searches for reports on the treatment of PCAs with FDs, we conducted a systematic review of the literature on its clinical efficacy and safety using random-effect binomial meta-analysis. RESULTS: We included 14 studies, which reported on a total of 225 PCAs in 220 patients. Procedure-related good outcome rate was 79% (95% confidence interval (CI), 72 84), with significantly lower odds among patients with ruptured aneurysms and basilar artery aneurysms. Procedure-related mortality rate was 15% (95% CI 10 21), with significantly higher rates among patients with giant aneurysms and basilar artery aneurysms. The rate of complete aneurysm occlusion at 6-month digital subtraction angiography (DSA) was 84%. Ischemic stroke rate was 11%. Perforator infarction rate was 7%. Postoperative subarachnoid hemorrhage (SAH) rate was 3%. Intraparenchymal hemorrhage (IPH) rate was 4%. CONCLUSIONS: Flow diverter treatment of PCAs is an effective method, which provides a high rate of complete occlusion at 6-month DSA. However, compared with anterior circulation aneurysms, patients with PCAs are at significantly higher risk of mortality, ischemic stroke and perforator infarction. Our findings indicate that, in most clinical centers, flow diverter treatment of PCAs should be conducted in carefully selected patients with poor natural history and no optimal treatment strategy. For ruptured and giant basilar artery aneurysms, there is still no good treatment option. PMID- 26801483 TI - Immunoadsorption therapy for dilated cardiomyopathy using tryptophan column-A prospective, multicenter, randomized, within-patient and parallel-group comparative study to evaluate efficacy and safety. AB - Over the past few decades, several cardiac autoantibodies have been reported in sera from patients with dilated cardiomyopathy (DCM). Immunoadsorption (IA) therapy is one of the therapeutic tools to remove such autoantibodies. The objective of this study was to investigate functional effects of IA therapy using a tryptophan column in severe DCM patients. Of 49 patients enrolled, 44 were randomized from 10 sites in Japan. IA therapy was conducted in 40 patients with DCM (refractory to standard therapy for heart failure, New York Heart Association [NYHA] class III/IV, left ventricular ejection fraction [LVEF] <30%). Mean echocardiographic LVEF was significantly improved (23.8 +/- 1.3% to 25.9 +/- 1.3%, P = 0.0015). However, mean radionuclide LVEF over 3 months of IA therapy was not significantly improved (20.8 +/- 1.1% to 21.9 +/- 1%, P = 0.0605). The cardiothoracic ratio was also significantly decreased (P = 0.0010). NYHA functional class (P < 0.0001), subjective symptoms assessed by a quality of life questionnaire (P = 0.0022), maximum oxygen consumption (P = 0.0074), and 6-minute walk distance (P = 0.0050) were improved after IA therapy. Subgroup analysis revealed improvement of echocardiographic LVEF in patients with higher baseline autoantibody scores but not in those with lower scores. IA therapy improved subjective symptoms and exercise capacity in patients with refractory heart failure resulting from DCM. Favorable effect on cardiac function was noted in patients with higher autoantibody scores. J. Clin. Apheresis 31:535-544, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26801484 TI - TLR4 preconditioning is associated with low success of OK-432 treatment for lymphatic malformations in children. AB - PURPOSE: We have recently shown that the relative TLR4 expression on monocytes of low responding pediatric patients after OK-432 treatment is significantly reduced after stimulation with lipopolysaccharide (LPS) compared with high responding children. The aim of this study was to perform further analysis to explain this observation. METHODS: Monocytes from children with high (HR, n = 5) and low response (LR, n = 6) after previous OK-432 treatment were stimulated with LPS for 20 h and analyzed with fluorescence-activated cell sorting (mean fluorescence intensity, MFI; level of significance P <= 0.05). RESULTS: Mean MFI after LPS stimulation was comparable in both groups (HR 1142 +/- 652 units, LR 839 +/- 427 units, P = 0.85). Significant changes after LPS stimulation are explained by higher pre-stimulation values in the LR group compared with the HR group (950 +/- 718 vs. 477 +/- 341, P = 0.25) with considerable differences of the mean expression changes after LPS stimulation (HR 665 +/- 683 vs. LR -111 +/- 605, P = 0.08). CONCLUSION: The previously shown reduced TLR4 upregulation on monocytes after LPS stimulation in the LR group compared with the HR group can be primarily explained by TLR preconditioning. This observation implies the use of absolute values with definite thresholds. PMID- 26801485 TI - Elevation of cardiac troponin T in patients with amyotrophic lateral sclerosis. AB - Limited evidence suggests that specificity of cardiac troponin T (cTnT), a highly sensitive biomarker of myocardial injury, is reduced in patients with skeletal myopathies. Whether amyotrophic lateral sclerosis (ALS)-the most common motor neuron disease-could be also associated with abnormal plasma or serum cTnT levels remains unclear. Our objective was to assess cTnT levels in patients with ALS without known cTnT elevating conditions. Among ALS patients seen at our institution until 2012 we identified those who had their cTnT measured. Patients who suffered from conditions known to elevate cTnT were excluded. A case-control analysis comparing cTnT levels of these ALS patients to matched non-ALS controls fulfilling the same inclusion criteria was performed. We included 40 ALS patients of whom 27 (68 %) patients had a positive cTnT. In the control group (n = 40), 2 (5 %) tested as cTnT positive (p < 0.001). Among the ALS patients who underwent cTnT evaluation on more occasions (n = 7; median follow-up = 1.08 years), 2 (29 %) patients tested positive during the initial measurement while 6 (86 %) of them had positive cTnT at the subsequent evaluations. ALS patients with increased cTnT had been diagnosed with ALS significantly earlier than those without the elevation. Our findings raise the possibility that ALS may cause cTnT elevations. Further studies are needed to confirm these findings, clarify the pathophysiological mechanism, and establish the significance of cTnT elevations in patients with ALS. PMID- 26801486 TI - Urgent need to improve the quality of case report in traditional Chinese medicine: Assessment on reporting quality of 3,417 cases. AB - OBJECTIVE: To survey the reporting quality of traditional Chinese medicine (TCM) case reports published in recent years and understand the common problems. The assessment results would lay the foundation for the development of recommendations for case report in Chinese medicine. METHODS: This survey determined the reporting quality of cases with Chinese herbal decoction, Chinese proprietary medicine, acupuncture, moxibustion and other traditional therapies published in 20 core medical journals of China by searching the China Academic Journals Full-text Database from 2006 to 2010. Fifty survey items in 16 domains were used to determine the reporting quality. One point was assigned to each item (Yes=1 point; No=0 point), and total score was 50 points. The domain of treatment was assessed independently, ranging from 2 to 9 items for different TCM interventions. RESULTS: The total of 1,858 case reports, covering 3,417 cases were included to analyze from 13 out of 20 core medical journals of China. There were 74.8% of them did not identify the nature of study in title, while 73.9% did not comprise an abstract. Incomplete reporting was found in discussions/ comment, and only 38.9% had made recommendations or take-away messages. Figures and tables were infrequently used. Three cases cited the full names of patients, but without declaring that any consent was obtained. Over 90% reported the symptoms and signs of TCM, and characteristics on tongue and pulse, but less than 50% did mention other medical history and diagnostic rationale. More than 90% treatments of the included cases were herbal decoction, with clear reporting on the ingredients and dosages. However, the reporting rate of the dosages of each ingredient was just 48.4%. Almost none reported the quality control of crude herbs, manufacturers and lot numbers of herbal proprietary medicine. Besides, advices and precautions on diet, emotions and living were rare to be illustrated. CONCLUSION: Systematic reporting recommendations are urged to develop for improving the contents and format of case reports in TCM. PMID- 26801487 TI - A bruised dimple on an injured elbow: what does it mean? PMID- 26801488 TI - Acute wrist pain. PMID- 26801489 TI - Towards evidence based emergency medicine: Best BETs from the Manchester Royal Infirmary. BET 1: Targeted blood pressure management in the hyperacute and acute stages following spontaneous intracerebral haemorrhage. AB - A short cut review was carried out to establish whether targeted blood pressure management in the hyperacute and acute stages following spontaneous intracerebral haemorrhage. 275 papers were found of which 6 presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. The clinical bottom line is the current evidence suggests in patients with hypertension following spontaneous intracerebral haemorrhage, intensive lowering of SBP to a target of less than 140mmHg in the hyperacute and acute stages is safe and may improve functional recovery. PMID- 26801491 TI - Towards evidence based emergency medicine: Best BETs from the Manchester Royal Infirmary. BET 2: Core stability versus conventional exercise for treating non specific low back pain. AB - A short cut review was carried out to establish whether core stability exercises are better than conventional exercise for treating non-specific low back pain. 6 papers were found of which 4 presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. The clinical bottom line is the perception that a core stability rehabilitation programme will improve low back pain has not been proven. PMID- 26801492 TI - Towards evidence based emergency medicine: Best BETs from the Manchester Royal Infirmary. BET 3: Advantages of ultrasound-assisted lumbar puncture. AB - A short cut review was carried out to establish ultrasound can assist. 9 papers were found of which 4 presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. The clinical bottom line is that using ultrasound assisted landmarks prior to LP improves success rate and reduces the number of attempts and traumatic taps. PMID- 26801493 TI - Climatic events inducing die-off in Mediterranean shrublands: are species' responses related to their functional traits? AB - Extreme climatic episodes, likely associated with climate change, often result in profound alterations of ecosystems and, particularly, in drastic events of vegetation die-off. Species attributes are expected to explain different biological responses to these environmental alterations. Here we explored how changes in plant cover and recruitment in response to an extreme climatic episode of drought and low temperatures were related to a set of functional traits (of leaves, roots and seeds) in Mediterranean shrubland species of south-west Spain. Remaining aerial green cover 2 years after the climatic event was positively related to specific leaf area (SLA), and negatively to leaf water potential, stable carbon isotope ratio and leaf proline content. However, plant cover resilience, i.e. the ability to attain pre-event values, was positively related to a syndrome of traits distinguished by a higher efficiency of water use and uptake. Thus, higher SLA and lower water-use efficiency characterized species that were able to maintain green biomass for a longer period of time but were less resilient in the medium term. There was a negative relationship between such syndromes and the number of emerging seedlings. Species with small seeds produced more seedlings per adult. Overall, recruitment was positively correlated with species die-off. This study demonstrates the relationship between plant traits and strong environmental pulses related to climate change, providing a functional interpretation of the recently reported episodes of climate-induced vegetation die-off. Our findings reveal the importance of selecting meaningful traits to interpret post-event resilience processes, particularly when combined with demographic attributes. PMID- 26801494 TI - Abundance-area relationships in bird assemblages along an Afrotropical elevational gradient: space limitation in montane forest selects for higher population densities. AB - The usual positive inter-specific relationship between range size and abundance of local populations can have notable exceptions in Afrotropical montane areas, where range-restricted bird species are unusually abundant. We tested how the area occupied locally by passerines and their geographic range size relate to local abundances along a tropical elevational gradient of Mt Cameroon, West Central Africa. Data on bird assemblages were collected at six forested elevations (350, 650, 1100, 1500, 1850 m, 2200 m a.s.l.) using a standardised point count at 16 locations per elevation. Elevational ranges of birds were compiled from published sources and their geographic range sizes were determined as the occupancy of 1 degrees x 1 degrees grid cells. The observed relationship between local abundance and geographic range size within the entire passerine assemblage on Mt Cameroon disagrees with the most frequently reported positive pattern. However, the patterns differ among elevations, with positive trends of the abundance-range size relationship in lowland changing to negative trends towards higher elevations. Interestingly, the total assemblage abundances do not differ much among elevations and population size estimates of species occupying different parts of the gradient remain relatively constant. These patterns are caused by relatively high abundances of montane species, which might be a result of long-term ecological specialization and/or competitive release in species-poor montane locations and possibly facilitated by an extinction filter. Our data suggest that montane species' abilities to maintain dense populations might compensate for less area available near mountain tops and help these populations to circumvent extinction. PMID- 26801495 TI - Inhibition in Clark's nutcrackers (Nucifraga columbiana): results of a detour reaching test. AB - Inhibition (i.e. the ability to restrain ineffective responses to a given stimulus) is a good indicator of complex cognitive abilities in animals. Inhibition has been demonstrated in a broad range of mammals with foraging style and social group size identified as potential influences of this ability. Whether these ecological factors also apply to birds has not been well studied. Corvids, a family of birds well known for being able to accomplish difficult cognitive tasks often requiring inhibition, are a good model for studying inhibitory control. During this study, we measured the ability of Clark's nutcrackers (Nucifraga columbiana), a relatively non-social, food specialist corvid to exercise inhibitory control during a detour-reaching test. Individuals had to retrieve a pine nut inserted into a transparent tube through one of the side openings without pecking directly at the nut from the front of the tube. Overall, nutcrackers were able to inhibit pecking directly at the food (i.e. prepotent response), instead detouring to the side to retrieve the reward. However, the nutcrackers first required a learning period before showing inhibitory control. The nutcrackers' ability to inhibit was lower than other corvids studied to date, and we discuss the implications of this result for the role of sociality and dietary breadth for the evolution of inhibitory control. PMID- 26801496 TI - Preference for and discrimination of videos of conspecific social behavior in mice. AB - We showed mice videos of three conspecific social behaviors, namely sniffing, copulation, and fighting, in pairwise combinations using iPods and evaluated preference as determined by time spent in front of each iPod. Mice preferred the copulation video to the sniffing video, the fighting video to the sniffing video, and the fighting video to the copulation video. In Experiment 1a, we used a single video clip for each social behavior but used multiple video clips for each social behavior in Experiment 2a. Next, we trained mice to discriminate between the fighting and copulation videos using a conditioned-place-preference-like task in which one video was associated with injection of morphine and the other was not. For half of the subjects, the fighting video was associated with morphine injection, and for the other half, the copulation video was associated with morphine injection. After conditioning, the mice stayed longer in the compartment with the morphine-associated video. When tested with still images obtained from the videos, mice stayed longer in the compartment with still images from the video associated with morphine injection (Experiment 1b). When we trained mice with multiple exemplars, the subjects showed generalization of preference for new video clips never shown during conditioning (Experiment 2b). These results demonstrate that mice had a preference among videos of particular behavior patterns and that they could discriminate these videos as visual category. Although relationship between real social behaviors and their videos is still open question, the preference tests suggest that the mice perceived the videos as meaningful stimuli. PMID- 26801498 TI - Impact of length of stay for first psychiatric admissions on the ratio of readmissions in subsequent years in a large Brazilian catchment area. AB - PURPOSE: This study aims to verify the impact that the length of stay has on the rates of readmission for patients who were first admitted to various inpatient psychiatric units in a large catchment area in a middle-income country. METHODS: The study included all patients who were first admitted to the 108 acute psychiatric beds available in the catchment area of Ribeirao Preto, Brazil, for a period of 8 years. Demographic features, inpatient unit of discharge, diagnosis and length of stay were assessed by bivariate analysis. An analysis of the time span between first admission and readmission was also conducted using survival curves estimated by the Kaplan-Meier formula. For the analyses of the risk of readmissions, a logistic regression analysis was conducted. RESULTS: From a total of 6261 patients admitted in the period of the survey, approximately one-third (2006) had at least one other readmission during the follow-up period. The rates per year of early readmission (within 90 days after discharge) varied from 16.1 to 20.9 %. The risk of readmission was higher immediately after discharge. The survival analysis showed that ultrashort length of stay (1-2 days) was associated with reduced odds of readmission, but multivariate logistic analysis showed no association between length of stay and the odds of readmissions. The predictors of early readmission included the diagnosis of depressive, bipolar, psychotic, and non-alcohol-related disorders, younger ages and unemployment. CONCLUSIONS: Duration of the first psychiatric admission was not associated with a higher risk of readmissions. Predictors for early readmissions of first-time-admitted psychiatric patients seem to be more related to the severity of the psychiatric diagnosis and demographic characteristics. PMID- 26801497 TI - Elevated methylation and decreased serum concentrations of BDNF in patients in levomethadone compared to diamorphine maintenance treatment. AB - Brain-derived neurotrophic factor (BDNF) appears to play a crucial role in the reward response to drugs such as heroin. The primary objective of the present study was to examine epigenetic changes and serum levels of BDNF in patients undergoing different opiate-based maintenance treatments. We compared patients receiving treatment with either levomethadone (n = 55) or diamorphine (n = 28) with a healthy control group (n = 51). When comparing all subjects (patients and controls), BDNF serum levels showed a negative correlation with the BDNF IV promoter methylation rate (r = -0.177, p = 0.048). Furthermore, BDNF serum levels negatively correlated with Beck's Depression Inventory measurements (r = -0.177, p < 0.001). Patients receiving diamorphine maintenance treatment showed slightly decreased BDNF serum levels compared to healthy controls, whereas patients on levomethadone maintenance treatment with or without heroine co-use showed a pronounced decrease (analysis of covariance: control vs. levomethadone with and without heroine co-use: p < 0.0001, diamorphine vs. levomethadone with heroine co use: p = 0.043, diamorphine vs. levomethadone without heroine co-use: p < 0.0001). According to these findings, methylation of the BDNF IV promoter showed the highest level in patients receiving levomethadone without heroine co-use (linear mixed model: control vs. levomethadone group without heroine co-use: p = 0.008, with heroin co-use: p = 0.050, diamorphine vs. levomethadone group with heroine co-use: p = 0.077 and without heroine co-use: p = 0.015.). For the first time, we show an epigenetic mechanism that may provide an explanation for mood destabilization in levomethadone maintenance treatment. PMID- 26801499 TI - Childhood Anti-NMDA Receptor Encephalitis. AB - OBJECTIVES: To study the clinical profile, and outcome of children with anti-N methyl-D-aspartate receptor (NMDAR) encephalitis. METHODS: This is a retrospective case series of children <12 y of age, diagnosed with anti-NMDAR encephalitis at a tertiary care institute during the period, May 2013 through June 2015. RESULTS: Twenty patients were tested for suspected anti-NMDAR encephalitis over this 2 y period. Of these, six children were positive for anti NMDAR antibodies. Four of these six children had completed treatment and two are currently receiving immunotherapy. Behavioral changes, psychosis, seizures and oro-lingual-facial dyskinesia were the presenting features. Extreme irritability, insomnia and mutism were noted in all the children. The symptoms were persistent, and the course was progressive over 4-8 wk duration. Neuroimaging and electroencephalography were non-specific. Intravenous pulse methylprednisolone and immunoglobulins were used as first-line therapeutic agents. Only one patient responded to first line immunotherapy; five out of six children required second line immunotherapy. One patient recovered following rituximab, and two patients showed a good response to cyclophosphamide pulse therapy; two patients are currently under treatment with second line immunotherapeutic agents. Tumor screen was negative in all children. CONCLUSIONS: Anti-NMDAR encephalitis is rare but a potentially treatable condition. Timely recognition is essential because treatment is entirely different from other viral encephalitis. Aggressive immunotherapy is the key to a favourable outcome. PMID- 26801500 TI - Musculoskeletal Evaluation of Children with Cerebral Palsy. AB - Cerebral Palsy (CP) is the most common chronic disability of childhood. The problems involved are complex; not only do these children have problems of mobility, but a plethora of associated problems [1]. A recent definition of CP includes secondary musculoskeletal problems [2]. The inclusion of this in the definition recognises the significance of musculoskeletal problems and the impact these problems have on the lives of children with CP and their families. Orthopedic management of the child with CP aims to reduce the impact of these musculoskeletal problems to help the child with CP to reach his maximum potential [3]. To accurately assess children and prepare management plans, a combination of medical history, physical examination, functional assessment, medical imaging, observational and instrumented gait analysis, and assessment of patient and family goals must be interpreted [4]. A detailed annual orthopedic assessment for all children with CP is recommended [5]. For an ambulant child, more frequent assessments are required during periods of rapid growth, observed deterioration in physical examination measures, and after interventions, including gait correction surgery. For a non-ambulant child, more frequent assessments are indicated according to hip surveillance guidelines [6, 7], during periods of observed deterioration, and following interventions such as hip or spine surgery. A systematic and practiced routine is conducive to efficiency and accuracy [5]. This paper discusses the Physical Examination Protocol used by the Hugh Williamson Gait Analysis Laboratory, in Melbourne, Australia. PMID- 26801501 TI - Defective Leukocyte Adhesion and Chemotaxis Contributes to Combined Immunodeficiency in Humans with Autosomal Recessive MST1 Deficiency. AB - PURPOSE: To investigate the clinical and functional aspects of MST1 (STK4) deficiency in a profoundly CD4-lymphopenic kindred with a novel homozygous nonsense mutation in STK4. Although recent studies have described the cellular effects of murine Mst1 deficiency, the phenotype of MST1-deficient human lymphocytes has yet to be fully explored. Patient lymphocytes were therefore investigated in the context of current knowledge of murine Mst1 deficiency. METHODS: Genetic etiology was identified by whole exome sequencing of genomic DNA from two siblings, combined with linkage analysis in the wider family. MST1 protein expression was assessed by immunoblotting. The ability of patient lymphocytes to adhere to ICAM-1 under flow conditions was measured, and transwell assays were used to assess chemotaxis. Chemokine receptor expression was examined by flow cytometry and receptor signalling by immunoblotting. RESULTS: A homozygous nonsense mutation in STK4 (c.442C > T, p.Arg148Stop) was found in the patients, leading to a lack of MST1 protein expression. Patient leukocytes exhibited deficient chemotaxis after stimulation with CXCL11, despite preserved expression of CXCR3. Patient lymphocytes were also unable to bind effectively to immobilised ICAM-1 under flow conditions, in keeping with a failure to develop high affinity binding. CONCLUSION: The observed abnormalities of adhesion and migration imply a profound trafficking defect among human MST1-deficient lymphocytes. By analogy with murine Mst1 deficiency and other defects of leucocyte trafficking, this is likely to contribute to immunodeficiency by impairing key aspects of T-cell development and function such as positive selection in the thymus, thymic egress and immune synapse formation in the periphery. PMID- 26801502 TI - Effect of leaking capillaries and microaneurysms in the perifoveal capillary network on resolution of macular edema by anti-vascular endothelial growth factor treatment. AB - PURPOSE: To investigate the effect of leaking capillaries and microaneurysms (MAs) in the perifoveal capillary network (PCN) on the treatment of fovea involving macular edema (ME) secondary to branch retinal vein occlusion (BRVO) by intravitreal ranibizumab (IVR) injections combined with focal, grid, and scatter laser photocoagulation. METHODS: Retrospective comparative case series. The MA (+) group consisted of 12 patients with leaking MAs in the PCN and the MA (-) group contained 11 patients without. At 6 months following the initial IVR injection, best corrected visual acuity (BCVA) was evaluated as the primary outcome. Secondary outcomes included central macular thickness (CMT) and the number of IVR injections performed in a pro re nata (PRN) regimen when CMT was >=300 um and vision deteriorated by 0.1 logMAR or greater. RESULTS: Mean BCVA improved by 0.30 +/- 0.25 logMAR in the MA (-) group and 0.28 +/- 0.20 logMAR in the MA (+) group (both P < 0.0001). Mean CMT was reduced by 237.6 +/- 221.4 um (P < 0.0001) in the MA (-) and 158.2 +/- 152.1 um (P < 0.01) in the MA (+) group. The degrees of improvement in BCVA (P = 0.74) and CMT (P = 0.33) did not vary significantly between the groups. The mean number of additional IVR injections was significantly less in the MA (-) group than in the MA (+) group (2.2 +/- 1.0 vs 3.0 +/- 0.8; P = 0.04). CONCLUSIONS: Although leaking MAs and capillaries in the PCN did not adversely affect improvements in BCVA and CMT, these manifestations led to an increased number of IVR injections needed to sustain resolution of ME involving the fovea. PMID- 26801503 TI - MicroRNA-455 suppresses non-small cell lung cancer through targeting ZEB1. AB - MicroRNA-455 (miRNA-455), which is downregulated in human cancer, potently mediates the multiple steps of carcinogenesis. However, the role of miR-455 in non-small cell lung cancer (NSCLC) carcinogenesis remains unclear. In present study, we determined the mature miRNA-455 expression in NSCLC tissues and cells by real-time PCR. Follow-up studies examined the effects of a miR-455 mimic (gain of function) on cell proliferation, migration, and invasion. Our data indicate that miR-455 was significantly down-regulated in NSCLC cell lines and tissues. In functional assays, overexpression of miR-455 suppressed the proliferation, migration, and invasion of NSCLC cell lines. Data from reporter assays showed that miR-455 directly binds to 3'UTR of ZEB1 and suppresses the endogenous level of ZEB1 protein expression. Furthermore, overexpression of ZEB1 reverses miR-455 suppressed malignant phenotype of NSCLC cells. Moreover, we found that upregulation of ZEB1 expression is inversely associated with miR-455 expression in NSCLC tissues. Taken together, miR-455 as an anti-oncogene in non-small cell lung cancer through up-regulation of ZEB1 and serve as a potential therapeutic target in NSCLC. PMID- 26801505 TI - New Portal-Superior Mesenteric Vein Reconstructions Using First Jejunal Vein Flap in Pancreaticoduodenectomy. AB - Pancreaticoduodenectomy (PD) is the only potential treatment for pancreatic head adenocarcinomas, which are sometimes located close to or invade the portal superior mesenteric vein (PSMV). Surgeons often attempt to obtain a negative resectional margin after resection of the PSMV. This attempt requires PSMV reconstruction through graft replacements or end-to-end anastomosis; however, possible complications should be concerned including anastomosis stenosis, damage to some of the PSMV branches, prosthetic graft infection, and that associated with autologous graft harvesting. The first jejunal artery and vein are often resected in PD with the intent of lymphadenectomy. In this study, jejunal vein flap was used for PSMV reconstruction without causing damage to any of the PSMV branches in two patients. Here, we describe the new methods of PSMV reconstruction using first jejunal vein flap in PD. PMID- 26801504 TI - Assessing Early Life Factors for Eosinophilic Esophagitis: Lessons From Other Allergic Diseases. AB - OPINION STATEMENT: Few studies have been conducted to investigate possible early life determinants for eosinophilic esophagitis. An improved understanding of the etiologic factors implicated in disease development would further elucidate possible disease pathogenesis, inform therapeutic targets for disease treatment, and identify possible modifiable factors for disease prevention in genetically susceptible individuals. Although eosinophilic esophagitis is increasing in incidence and prevalence, the disease remains relatively rare, posing challenges for studying etiologic factors in disease development. Eosinophilic esophagitis is believed to be antigen-mediated, and most patients with EoE have concomitant atopic disease. In recent years, the evolution of our understanding of possible etiologic mechanisms in allergic disease has been informed by our understanding of how early life perturbations can lead to dysbiosis in the colonization of the microflora in the gastrointestinal tract and subsequent dysregulated immune development. Perturbations include factors such as antibiotic use, including prenatal, intra-antepartum, and infancy use of antibiotics, Cesarean delivery, preterm delivery, and neonatal intensive care admission. This article provides a review of these recent developments, as they relate to atopic disease, to inform future directions in the study of early life etiologic factors in the development of eosinophilic esophagitis. PMID- 26801506 TI - Surgical Apgar Score Predicted Postoperative Morbidity After Esophagectomy for Esophageal Cancer. AB - BACKGROUND: Recently, a simple and easy complication prediction system, the Surgical Apgar Sore (SAS) calculated by three intraoperative parameters (estimated blood loss, lowest mean arterial pressure, and lowest heart rate), has been proposed for general surgery. This study aimed to determine if the SAS could accurately predict perioperative morbidity in patients undergoing esophagectomy for esophageal cancer. METHODS: We investigated 399 patients who underwent esophagectomy at the Kumamoto University Hospital between April 2007 and March 2015. Clinical data, including intraoperative parameters, were collected retrospectively. Patients had postoperative morbidities classified as Clavien Dindo grade III or more. Univariate and multivariate analyses were performed to elucidate factors that affected the development of complications. RESULTS: The mean age of the study population was 65.7 years, 357 patients (89.5 %) were male. The frequency of any morbidity was 32.3 %. Univariate analyses showed that the SAS as well as preoperative chemotherapy, volume of bleeding, and reconstruction of organs were associated with morbidities. Multivariate analysis showed that a SAS < 5 was found to be an independent risk factor for morbidities. CONCLUSION: The SAS is considered to be useful for predicting the development of postoperative morbidities after esophagectomy for esophageal cancer. PMID- 26801508 TI - Hard Copy Durable Patient Cancer Education Materials: Do They Still Matter? AB - Traditional hard copy information materials are still present in our cancer clinics. While their actual impact on patient care often goes un-assessed, it is important to understand their role in today's electronic age where information can easily be obtained from various sources. It has remained the practice in our melanoma clinic to provide an information booklet to all of our new patients. The purpose of this study was to evaluate how useful this booklet was, as well as determine the current resources our patients use to gather cancer information. All patients referred to the clinic in the previous 3 years were pooled from our prospective, IRB-approved, melanoma sentinel node database. Of these 205 patients, a valid email address was listed for 147. A ten-question survey was emailed to all of these patients, who were not told ahead of time that their experience with the booklet would be studied. Seventy-seven of the 147 (52 %) patients polled responded. Fifty-eight (75 %) remembered receiving the booklet at their initial consultation. Forty-four (76 %) of those patients rated it as extremely or very useful, and no patients reported the booklet as not useful at all. Eighty-eight percent of respondents found the information to be clear and helpful. Sixty-four percent remembered the provider reviewing the material with them, and nearly all of these patients found that helpful. When asked to rank the importance of the various resources for obtaining cancer information, providers were ranked as most important, followed by the information booklet and Internet information sites. Internet blogs and friends and family were rated as the least important sources of information. Even in the current electronic age, our results indicate that information shared by providers, including the hard copy education booklet, was the most important source of information for our newly referred melanoma patients. PMID- 26801507 TI - Surgical Results and Oncologic Outcomes for Rectal Cancer with Tailored Mesorectal Excision over Two Decades. AB - OBJECTIVE: This study aimed to compare the characteristics of the tumors, the management strategy, and oncologic outcomes of patients with rectal cancer surgery in these two periods: period 1 (1993-2001) and period 2 (2002-2011). METHODS: All patients who underwent radical resection of rectal cancer from 1993 to 2011 were included. Comparisons of the patients' demographics, characteristics, operating results, and oncologic outcome between the two periods were undertaken. RESULTS: Radical resection for rectal cancer was performed in 1611 patients (993 men). Patients were significantly older and more had comorbid medical diseases in period 2. More laparoscopic resections were performed and more patients had preoperative chemoradiation in period 2. The postoperative mortality was significantly lower and the hospital stay was significantly shorter in period 2. In those with non-metastatic cancer, the 5-year local recurrences of patients in period 1 and period 2 were 11.9 and 5.9 %, respectively. (p = 0.002) The patients in period 2 had significantly better 5-year overall (68.1 vs. 60.2 %, p = 0.003) and 5-year cancer-specific survival (76.1 vs. 69.4 %, p < 0.001) when compared with those treated in period 1. The improvement occurred mainly in patients with abdominoperineal resection and those with stage III diseases. In the multivariate analysis, among the other histological factors, operations performed in period 2 and laparoscopic surgery were independent factors associated with better overall survival. CONCLUSIONS: Significant improvement in the surgical outcomes in terms of a lower recurrence rate and better survival was achieved in the recent years with the increase in neoadjuvant therapy and the application of laparoscopic surgery. PMID- 26801510 TI - Racial Disparities in Emotional Distress Among Cancer Survivors: Insights from the Health Information National Trends Survey (HINTS). AB - The purpose of this study was to examine the impact of race, cancer history, and their interaction on emotional distress among a nationally representative sample of US adults. Data utilized for this analysis were obtained from the first, second, and fourth iterations of the fourth cycle of the Health Information National Trends Survey (HINTS). The study sample included 3959, 3630, and 3677 respondents for the years 2011, 2012, and 2014, respectively, for a total sample size of 11,266. A multivariable ordered logistic regression model was used to assess the relationship between emotional distress, race, and cancer history. The effect of cancer history on emotional distress was found to be moderated by race. Specifically, emotional distress was significantly higher among African American cancer survivors. Factors found to be protective against emotional distress included healthy lifestyle, older age, and higher income. Factors associated with high levels of emotional distress included poor general health status, low self efficacy, and being female. The authors recommend the design, advancement, and implementation of evidence-based culturally sensitive interventions aimed at effectively screening and managing psychological distress symptoms, particularly among African American long-term cancer survivor patient populations. PMID- 26801509 TI - A Dialogue of Depression and Hope: Elderly Patients Diagnosed with Cancer and Their Spousal Caregivers. AB - In the next few decades, a significant increase in the number of elderly survivors diagnosed with cancer is anticipated due to an increase in life expectancy and better medical treatments. The reality of being old and being diagnosed with cancer may limit considerably the future time perspective (time expected to live) of both the patient and his or her caregiver(s) and lead then to invest resources in emotionally meaningful goals and close social relationships. The goal of the current study was to describe the relationship among psychological distress, depression, social support, and hope in a cohort of oldest old patients diagnosed with cancer and their spousal caregivers living at home. We predicted that patients would rely mostly on their hope and less on social as a source of coping. Our cross-sectional sample consisted of 45 patients with cancer and 45 spouses; all individuals were at least 86 years old. The participants completed standardized self-report measures of depression, distress, hope, and social support. Patients presented extremely high levels of psychological distress compared with their spousal caregivers, who exhibited significantly lower levels of distress and depression. Among patients, hope but not social support was found to be negatively correlated to distress. In order to enhance the quality of life of oldest old cancer patients and their spouses, health care teams should understand and address the unique needs of each individual within the dyads of patients and spouses in this group. PMID- 26801511 TI - A posttraumatic pontomedullary rent with good outcome. AB - Posttraumatic pontomedullary rents have been described mainly as postmortem histopathological findings in patients who died immediately or within the first hours after trauma. To the best of our knowledge, no long-term survivors of this condition have been described, and those surviving initially were always severely impaired. We present the first patient with this condition and with corresponding lesions on imaging who survived longer than 3 months. Moreover, the patient regained almost complete independence 1 year after the trauma. We briefly discuss the proposed mechanisms of this injury. We conclude that this lesion, when incomplete, is not always lethal and can exceptionally have a good clinical outcome. Prevention of respiratory failure is of utmost importance in these patients. PMID- 26801512 TI - Outcomes in meningitis/ventriculitis treated with intravenous or intraventricular plus intravenous colistin. AB - BACKGROUND: The aim of this work is to evaluate the outcome of patients treated with intrathecal colistin for meningitis/ventriculitis. METHODS: This retrospective case series study included patients presenting with nosocomial meningitis/ventriculitis following neurosurgical interventions and having intravenous (IVC group) or intravenous and intrathecal/intraventricular colistin (ITC group) treatment between 2006 and 2014. RESULTS: Thirty-four patients presented nosocomial meningitis/ventriculitis; 11 (32.5 %) were included in the IVC group and 23 (67.6 %) in the ITC group. The most frequent isolated bacteria were Acinetobacter baumannii. The mean dose was 170,000 (+/-400) IU and the duration of intraventricular treatment was 16.0 (+/-8.3) days. The duration of intravenous treatment was 16.0 (+/-8.3) days in the ITC group and 15.3 +/- 7.6 days in IVC group. Hospital mortality was significantly lower in the ITC group compared with the IVC group (13 vs. 72.7 %, p = 0.001). CONCLUSIONS: The combination of intravenous plus intraventricular (IV-IVT) colistin therapy may improve outcomes in patients attending with meningitis/ventriculitis due to multi drug resistance infections. PMID- 26801513 TI - Fronto-temporal branch of facial nerve within the interfascial fat pad: is the interfascial dissection really safe? AB - BACKGROUND: The study was conducted to clarify the presence or absence of fronto temporal branches (FTB) of the facial nerve within the interfascial (between the superficial and deep leaflet of the temporalis fascia) fat pad. METHODS: Eight formalin-fixed cadaveric heads (16 sides) were used in the study. The course of the facial nerve and the FTB was dissected in its individual tissue planes and followed from the stylomastoid foramen to the frontal region. RESULTS: In the fronto-temporal region, above the zygomatic arch, FTB gives several small twigs running anteriorly in the fat pad above the superficial temporalis fascia and a branch within the temporo-parietal fascia (TPF) to the muscles of the forehead. There were no twigs of the FTB within the interfascial fat pad. CONCLUSIONS: No branches of the FTB are found in the interfascial (between the superficial and deep leaflet of the temporalis fascia) fat pad. The interfascial dissection can be safely performed without risk of injury to the FTB and potential subsequent frontalis palsy. PMID- 26801514 TI - Somatostatin treatment can induce extensive fibrosis in growth hormone-producing adenoma. PMID- 26801515 TI - Exposure to persistent organic pollutants and sperm DNA methylation changes in Arctic and European populations. AB - Persistent organic pollutants (POPs), such as PCBs (polychlorinated biphenyls) and DDT [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane], are environmental contaminants with potential endocrine disrupting activity. DNA methylation levels in peripheral blood lymphocytes have been associated with serum concentrations of POPs in Greenland Inuit and Korean populations. Greenland Inuits are characterized by the highest worldwide POP levels. In this cross-sectional study we evaluated the relationship between serum POP concentrations and DNA methylation levels in sperm of non-occupationally exposed fertile men from Greenland, Warsaw (Poland), and Kharkiv (Ukraine). Serum levels of PCB-153 [1,2,4 trichloro-5-(2,4,5-trichlorophenyl)benzene], as a proxy of the total PCBs body burden, and of p,p'-DDE [1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene], the main metabolite of DDT were measured. Sperm DNA methylation level was assessed globally by flow cytometric (FCM) immunodetection of 5-methyl-cytosines and at specific repetitive DNA sequences (Alu, LINE-1, Satalpha) by PCR-pyrosequencing after bisulfite conversion. Multivariate linear regression analysis was applied to investigate correlations between serum POP concentrations and DNA methylation. No consistent associations between exposure to POPs and sperm DNA methylation at repetitive DNA sequences were detected. A statistically significant global decrease in methylation was associated with exposure to either POP by FCM analysis. This is the first study to investigate environmental exposure to POPs and DNA methylation levels considering sperm as the target cells. Although POP exposure appears to have a limited negative impact on sperm DNA methylation levels in adult males, the global hypomethylation detected by one of the methods applied suggests that further investigation is warranted. PMID- 26801516 TI - The use of a proteinaceous "cushion" with a polystyrene-binding peptide tag to control the orientation and function of a target peptide adsorbed to a hydrophilic polystyrene surface. AB - In immobilizing target biomolecules on a solid surface, it is essential (i) to orient the target moiety in a preferred direction and (ii) to avoid unwanted interactions of the target moiety including with the solid surface. The preferred orientation of the target moiety can be achieved by genetic conjugation of an affinity peptide tag specific to the immobilization surface. Herein, we report on a strategy for reducing the extent of direct interaction between the target moiety and surface in the immobilization of hexahistidine peptide (6His) and green fluorescent protein (GFP) on a hydrophilic polystyrene (PS) surface: Ribonuclease HII from Thermococcus kodakaraensis (cHII) was genetically inserted as a "cushion" between the PS-affinity peptide tag and target moiety. The insertion of a cushion protein resulted in a considerably stronger immobilization of target biomolecules compared to conjugation with only a PS affinity peptide tag, resulting in a substantially enhanced accessibility of the detection antibody to the target 6His peptide. The fluorescent intensity of the GFP moiety was decreased by approximately 30% as the result of fusion with cHII and the PS affinity peptide tag but was fully retained in the immobilization on the PS surface irrespective of the increased binding force. Furthermore, the fusion of cHII did not impair the stability of the target GFP moiety. Accordingly, the use of a proteinaceous cushion appears to be promising for the immobilization of functional biomolecules on a solid surface. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:527-534, 2016. PMID- 26801517 TI - Agminated cellular blue naevi of the penis: dermoscopic, confocal and histopathological correlation of two cases. AB - Blue naevi may present rarely as multiple lesions grouped in a circumscribed area, described as agminated blue naevi. This clinical presentation may mimic metastatic malignant melanoma. We present two cases of agminated cellular blue naevi of the penis, with dermoscopy, reflectance confocal microscopy and histopathological correlation. Dermoscopy of the area showed multiple grouped lesions of homogeneous dark-brown to blue colour. Using reflectance confocal microscopy, focusing on the bluish areas, predominantly bright dendritic cells were visible at the dermoepidermal junction and papillary dermis, while in the brownish areas the presence of dendritic and bright cells predominated in the basal layer. Our patients are of special interest as they are the first cases, to our knowledge, reported of agminated blue naevi on the penis, studied by both dermoscopy and confocal microscopy, confirming the diagnosis with histopathological correlation. Moreover, one case represented a divided or 'kissing' blue naevus of the penis. PMID- 26801518 TI - Peste Des Petits Ruminants in Benin: Persistence of a Single Virus Genotype in the Country for Over 42 Years. AB - Peste des petits ruminants (PPR) is a contagious and often fatal disease affecting sheep and goats. Currently, it is endemic in Africa, the Middle and Near East, the Indian subcontinent and China. Understanding the molecular epidemiology and evolution of PPR virus (PPRV) can assist in the control of the transboundary spread of this economically important disease. We isolated PPRV from pathological and swab samples collected 42 years apart (1969 and 2011) in Benin, West Africa, and sequenced the full genome of two isolates (Benin/B1/1969 and Benin/10/2011). Phylogenetic analysis showed that all of the characterized isolates clustered within viral lineage II and that the 2011 isolates fell into two distinct subgroups. Comparison of the full genome sequences revealed a 95.3% identity at the nucleotide level, while at the protein level, the matrix protein was the most conserved between the two viruses with an identity of 99.7% and only one amino acid substitution over the 42-year sampling period. An analysis of specific amino acid residues of known or putative function did not identify any significant changes between the two viruses. A molecular clock analysis of complete PPRV genomes revealed that the lineage II viruses sampled here arose in the early 1960s and that these viruses have likely persisted in Benin since this time. PMID- 26801519 TI - Hematopoietic peripheral circulating blood stem cells as an independent marker of good transfusion management in patients with beta-thalassemia: results from a preliminary study. AB - BACKGROUND: Beyond hemoglobin (Hb) levels and performance status, further surrogate markers of appropriate transfusion management should improve the quality of thalassemia care. We investigated the levels of peripheral circulating CD34+ stem cells as an independent marker of appropriate hematopoietic balance in patients with thalassemia. STUDY DESIGN AND METHODS: Peripheral circulating CD34+ stem cells, colony-forming unitgranulocyte, erythrocyte, macrophage, magakaryocyte (CF-GEMM), colony-forming unitgranulocyte/macrophage (CFU-GM), and erythroidburst-forming units (BFU-E) were assayed, according to standard procedures. Patients with thalassemia major (TM) and thalassemia intermedia (TI) were tested and compared to healthy controls. Demographic and clinical data were recorded. RESULTS: Overall, 56 patients with TM (median age, 35 years; range, 13 52 years) and 13 with TI (median age, 44 years; range, 27-67 years) were evaluated. Annual red blood cell (RBC) transfusion requirements ranged from 10 to 65 units in all patients except four nontransfused cases. A significant increase in peripheral circulating stem cells was observed in patients, in comparison with healthy controls. Nontransfused patients showed the mean highest levels of stem cells (CD34, 32.5 +/- 14.8/MUL; BFU-E, 41.3 +/- 22.8/mL; CFU-GM, 19.6 +/- 5.6/mL; CFU-GEMM, 9.0 +/- 6.1/mL). CD34+ cell count was 6.9 +/- 4.5/MUL in TM (p = 0.014) and 11.8 +/- 14.8/MUL (p = 0.051) in TI. Furthermore, only in patients with TI was a significant increase in CFU-GEMM (3.0 +/- 4.8 vs. 0.75 +/- 2.05/mL, p = 0.0001) observed. At multivariate analysis, peripheral circulating CD34+ stem cells did not correlate with age, sex, smoking habit, number of RBCs units transfused, Hb levels, iron chelation therapy, history of splenectomy, and hypothyroidism. CONCLUSION: Circulating peripheral CD34 + stem cells are increased in beta-thalassemia, in particular in nontransfused patients, compared to healthy controls. PMID- 26801520 TI - MFN2-related genetic and clinical features in a cohort of Chinese CMT2 patients. AB - Charcot-Marie-Tooth disease 2A (CMT2A), caused by mutations in the mitofusin 2 gene (MFN2), is the most common CMT2 subtype. The aim of our study is to assess the frequency and summarize the genetic and clinical characteristics of Chinese CMT2A patients. A total of 17 coding exons of MFN2 were detected by direct sequencing in 82 unrelated Chinese families diagnosed as CMT2. Clinical evaluations were analyzed among CMT2A patients. We identified 14 missense variants in 9 sporadic and 6 familial cases, including four novel mutations (T129A, S249F, Q367P, and Q674L), 4 known mutations (R94W, R94Q, T105M, C132Y, M376V and Q751X), and 4 rare missense variants (K120E, C217F, K307E and T356S). A total of 23 patients had early-onset phenotype. Two patients had a CMTNS score of 0 to 10; 16 had a score of 11 to 20; and 7 had a score greater than 20. Five patients were confirmed a de novo origin. Six of 14 variants were located or closed to the GTPase domain. We report four novel mutations and four rare missense variants. MFN2 mutations account for 18% of CMT2 families in mainland China. The common characteristics of Chinese pedigree are early disease onset and moderate phenotypes. PMID- 26801522 TI - Amyloid precursor-like protein 1 (APLP1) exhibits stronger zinc-dependent neuronal adhesion than amyloid precursor protein and APLP2. AB - The amyloid precursor protein (APP) and its paralogs, amyloid precursor-like protein 1 (APLP1) and APLP2, are metalloproteins with a putative role both in synaptogenesis and in maintaining synapse structure. Here, we studied the effect of zinc on membrane localization, adhesion, and secretase cleavage of APP, APLP1, and APLP2 in cell culture and rat neurons. For this, we employed live-cell microscopy techniques, a microcontact printing adhesion assay and ELISA for protein detection in cell culture supernatants. We report that zinc induces the multimerization of proteins of the amyloid precursor protein family and enriches them at cellular adhesion sites. Thus, zinc facilitates the formation of de novo APP and APLP1 containing adhesion complexes, whereas it does not have such influence on APLP2. Furthermore, zinc-binding prevented cleavage of APP and APLPs by extracellular secretases. In conclusion, the complexation of zinc modulates neuronal functions of APP and APLPs by (i) regulating formation of adhesion complexes, most prominently for APLP1, and (ii) by reducing the concentrations of neurotrophic soluble APP/APLP ectodomains. Earlier studies suggest a function of the amyloid precursor protein (APP) family proteins in neuronal adhesion. We report here that adhesive function of these proteins is tightly regulated by zinc, most prominently for amyloid precursor-like protein 1 (APLP1). Zinc mediated APLP1 multimerization, which induced formation of new neuronal contacts and decreased APLP1 shedding. This suggests that APLP1 could function as a zinc receptor processing zinc signals to stabilized or new neuronal contacts. PMID- 26801523 TI - The 2016 International League of Dermatological Societies' revised glossary for the description of cutaneous lesions. AB - BACKGROUND: In order to facilitate effective communication in dermatology, a clearly defined glossary with precise descriptions is essential. The International League of Dermatological Societies' (ILDS) 'Glossary of basic dermatology lesions' was first published in 1987. A quarter of a century later, the ILDS made the decision to revise and expand this nomenclature. OBJECTIVES: Revision and expansion of an international nomenclature for the description of cutaneous lesions. METHODS: The ILDS nominated a committee on nomenclature. Based on a review of the literature and major textbooks, the committee assembled a list of terms and definitions. National member societies of the ILDS were then invited to participate in a Delphi voting exercise (two rounds for basic descriptive terms, one round for additional terms). The committee reviewed and consolidated comments and consented the final version. RESULTS: The revised and expanded version of the ILDS nomenclature includes 13 basic terms and over 100 additional descriptive terms. Forty-six and then 34 national member societies participated in the first and second voting rounds, respectively. CONCLUSIONS: A unifying nomenclature is crucial for effective communication among dermatologists and those who care for skin diseases. The next step will be a roll-out programme to national member societies of the ILDS that will include translations into languages other than English and adaptations reflecting local circumstances. PMID- 26801524 TI - Novel triterpene oxidizing activity of Arabidopsis thaliana CYP716A subfamily enzymes. AB - Triterpenoids have diverse chemical structures and bioactivities. Cytochrome P450 monooxygenases play a key role in their structural diversification. In higher plants, CYP716A subfamily enzymes are triterpene oxidases. In this study, Arabidopsis thaliana CYP716A1 and CYP716A2 were characterized by heterologously expressing them in simple triterpene-producing yeast strains. In contrast to the C-28 oxidative activity of CYP716A1 shown in several CYP716A subfamily enzymes, remarkably, CYP716A2 displayed 22alpha-hydroxylation activity against alpha amyrin that has not been previously reported, which produces the cytotoxic triterpenoid, 22alpha-hydroxy-alpha-amyrin. Our results contribute to the enrichment of the molecular toolbox that allows for the combinatorial biosynthesis of diverse triterpenoids. PMID- 26801521 TI - The effect of age and unilateral leg immobilization for 2 weeks on substrate utilization during moderate-intensity exercise in human skeletal muscle. AB - KEY POINTS: This study aimed to provide molecular insight into the differential effects of age and physical inactivity on the regulation of substrate metabolism during moderate-intensity exercise. Using the arteriovenous balance technique, we studied the effect of immobilization of one leg for 2 weeks on leg substrate utilization in young and older men during two-legged dynamic knee-extensor moderate-intensity exercise, as well as changes in key proteins in muscle metabolism before and after exercise. Age and immobilization did not affect relative carbohydrate and fat utilization during exercise, but the older men had higher uptake of exogenous fatty acids, whereas the young men relied more on endogenous fatty acids during exercise. Using a combined whole-leg and molecular approach, we provide evidence that both age and physical inactivity result in intramuscular lipid accumulation, but this occurs only in part through the same mechanisms. ABSTRACT: Age and inactivity have been associated with intramuscular triglyceride (IMTG) accumulation. Here, we attempt to disentangle these factors by studying the effect of 2 weeks of unilateral leg immobilization on substrate utilization across the legs during moderate-intensity exercise in young (n = 17; 23 +/- 1 years old) and older men (n = 15; 68 +/- 1 years old), while the contralateral leg served as the control. After immobilization, the participants performed two-legged isolated knee-extensor exercise at 20 +/- 1 W (~50% maximal work capacity) for 45 min with catheters inserted in the brachial artery and both femoral veins. Biopsy samples obtained from vastus lateralis muscles of both legs before and after exercise were used for analysis of substrates, protein content and enzyme activities. During exercise, leg substrate utilization (respiratory quotient) did not differ between groups or legs. Leg fatty acid uptake was greater in older than in young men, and although young men demonstrated net leg glycerol release during exercise, older men showed net glycerol uptake. At baseline, IMTG, muscle pyruvate dehydrogenase complex activity and the protein content of adipose triglyceride lipase, acetyl-CoA carboxylase 2 and AMP activated protein kinase (AMPK)gamma3 were higher in young than in older men. Furthermore, adipose triglyceride lipase, plasma membrane-associated fatty acid binding protein and AMPKgamma3 subunit protein contents were lower and IMTG was higher in the immobilized than the contralateral leg in young and older men. Thus, immobilization and age did not affect substrate choice (respiratory quotient) during moderate exercise, but the whole-leg and molecular differences in fatty acid mobilization could explain the age- and immobilization-induced IMTG accumulation. PMID- 26801525 TI - Expression of ZmGA20ox cDNA alters plant morphology and increases biomass production of switchgrass (Panicum virgatum L.). AB - Switchgrass (Panicum virgatum L.) is considered a model herbaceous energy crop for the USA, for its adaptation to marginal land, low rainfall and nutrient deficient soils; however, its low biomass yield is one of several constraints, and this might be rectified by modulating plant growth regulator levels. In this study, we have determined whether the expression of the Zea mays gibberellin 20 oxidase (ZmGA20ox) cDNA in switchgrass will improve biomass production. The ZmGA20ox gene was placed under the control of constitutive CaMV35S promoter with a strong TMV omega enhancer, and introduced into switchgrass via Agrobacterium mediated transformation. The transgene integration and expression levels of ZmGA20ox in T0 plants were analysed using Southern blot and qRT-PCR. Under glasshouse conditions, selected transgenic plants exhibited longer leaves, internodes and tillers, which resulted in twofold increased biomass. These phenotypic alterations correlated with the levels of transgene expression and the particular gibberellin content. Expression of ZmGA20ox also affected the expression of genes coding for key enzymes in lignin biosynthesis. Our results suggest that the employment of ectopic ZmGA20ox and selection for natural variants with high level expression of endogenous GA20ox are appropriate approaches to increase biomass production of switchgrass and other monocot biofuel crops. PMID- 26801553 TI - The early recognition inventory ERIraos assesses the entire spectrum of symptoms through the course of an at-risk mental state. AB - AIM: Functional disability and social consequences frequently occur at the prodromal stage of schizophrenia. Efforts to recognize an increasing risk of psychosis onset have thus become a topical issue worldwide. This is to introduce the English version of the ERIraos early-recognition inventory. METHODS: The ERIraos, developed in a systematic, empirical approach from the Instrument for the Retrospective Assessment of the Onset of Schizophrenia, incorporates basic symptoms from the Cologne Early Recognition Study. The research version also includes as further predictive items so-called brief limited intermittent psychotic symptoms and attenuated psychotic symptoms from the Comprehensive Assessment of At-Risk Mental States instrument. RESULTS: The ERIraos with its 15 item screening Checklist and 50-item Symptom List permits early recognition of psychosis risk in three steps of decreasing sensitivity and increasing specificity. Step 1 relies on patients' self-perception of symptoms, which prompt them to contact a primary health service. There, in Step 2, at-risk individuals are identified using the Checklist, characterized by a low-risk threshold, and referred to further examination using the Symptom List (Step 3). Information on symptom accumulation and increasing symptom severity enhances the instrument's predictive power. In a validation test, psychotic transitions increased linearly up to 50% over 2 years. Compared with other instruments and on the prodromal stage of depressive disorder, the ERIraos has shown good predictive capacity. CONCLUSIONS: The ERIraos has been successfully employed as a two-step tool for the early recognition of psychosis risk in several German studies and translated into several foreign languages. PMID- 26801554 TI - Postnatal lethality and abnormal development of foregut and spleen in Ndrg4 mutant mice. AB - NDRG4 is a member of the NDRG family (N-myc downstream-regulated gene), which is highly expressed in brain and heart. Previous studies showed that Ndrg1-deficient mice exhibited a progressive demyelinating disorder of peripheral nerves and Ndrg4-deficient mice had spatial learning deficits and vulnerabilities to cerebral ischemia. Here, we report generation of Ndrg4 mutant alleles that exhibit several development defects different from those previously reported. Our homozygous mice showed growth retardation and postnatal lethality. Spleen and thymuses of Ndrg4(-/-) mice are considerably reduced in size from 3 weeks of age. Histological analysis revealed abnormal hyperkeratosis in the squamous foregut and abnormal loss of erythrocytes in the spleen of Ndrg4(-/-) mice. In addition, we observed an abnormal hind limb clasping phenotype upon tail suspension suggesting neurological abnormalities. Consistent to these abnormalities, Ndrg4 is expressed in smooth muscle cells of the stomach, macrophages of the spleen and neurons. Availability of the conditional allele for Ndrg4 should facilitate further detailed analyses of the potential roles of Ndrg4 in gut development, nervous system and immune system. PMID- 26801555 TI - Vesicular monoamine transporter 2 (Vmat2) knockdown elicits anxiety-like behavior in zebrafish. AB - Vesicular monoamine transporter 2 (Vmat2) is widely distributed in the central nervous system, and responsible for uptaking transmitters into the vesicles. However, whether Vmat2-deficiency is related to the anxiety is rarely investigated, especially in zebrafish. Here, we reported Vmat2 heterzygous mutant zebrafish displayed anxiety-like behavior. The mutants spent less time in the top area and took longer latency to the top in the novel tank test. Consistently, they showed dark avoidance in the light/dark box test, with longer duration in the light zone and increased number of crossing between the two zones. Monoamine concentration analysis showed that the levels of monoamine neurotransmitters including dopamine (DA), 5-hydroxy tryptamine (5-HT) and norepinephrine (NE), as well as their metabolites were decreased in VMAT mutants. Taken together, these findings suggest that Vmat2 heterzygous mutant zebrafish may serve as a new model of anxiety, which may be related with the low level of DA, 5-HT and NE. PMID- 26801556 TI - Tribbles 3 inhibits brown adipocyte differentiation and function by suppressing insulin signaling. AB - Recent studies have demonstrated that adult humans have substantial amounts of functioning brown adipose tissue (BAT). Since BAT has been implicated as an anti obese and anti-diabetic tissue, it is important to understand the signaling molecules that regulate BAT function. There has been a link between insulin signaling and BAT metabolism as deletion or pharmaceutical inhibition of insulin signaling impairs BAT differentiation and function. Tribbles 3 (TRB3) is a pseudo kinase that has been shown to regulate metabolism and insulin signaling in multiple tissues but the role of TRB3 in BAT has not been studied. In this study, we found that TRB3 expression was present in BAT and overexpression of TRB3 in brown preadipocytes impaired differentiation and decreased expression of BAT markers. Furthermore, TRB3 overexpression resulted in significantly lower oxygen consumption rates for basal and proton leakage, indicating decreased BAT activity. Based on previous studies showing that deletion or pharmaceutical inhibition of insulin signaling impairs BAT differentiation and function, we assessed insulin signaling in brown preadipocytes and BAT in vivo. Overexpression of TRB3 in cells impaired insulin-stimulated IRS1 and Akt phosphorylation, whereas TRB3KO mice displayed improved IRS1 and Akt phosphorylation. Finally, deletion of IRS1 abolished the function of TRB3 to regulate BAT differentiation and metabolism. These data demonstrate that TRB3 inhibits insulin signaling in BAT, resulting in impaired differentiation and function. PMID- 26801557 TI - Peripheral and central localization of the nesfatin-1 receptor using autoradiography in rats. AB - Nesfatin-1 was recently identified and introduced as food intake-regulatory hormone. Soon thereafter, mounting evidence indicated a much broader role for nesfatin-1 with an involvement in the regulation of food intake, gastrointestinal motility, glucose homeostasis, blood pressure and stress. Despite the growing knowledge on the physiological regulation and functions of nesfatin-1, the receptor mediating these effects remains to be characterized. Therefore, the aim of this study was to investigate the peripheral and central localization of the nesfatin-1 receptor by autoradiography. Male Sprague-Dawley rats were used and peripheral as well as brain tissue was processed for (125)I-nesfatin-1 autoradiography. In peripheral tissues, an autoradiographic signal was observed in the gastric mucosa of corpus and antrum, in duodenum, jejunum and ileum, while no signal was detected in the colon. Preabsorption of (125)I-nesfatin-1 with non labeled nesfatin-1 greatly diminished the autoradiographic signal in the stomach indicating specificity (-32%, p < 0.001). A displacement assay showed an effective concentration by which 50% of (125)I-nesfatin-1 bound to the receptor (EC50) in the gastric corpus of 80 pM. Moreover, autoradiography was observed in endocrine tissues including the pituitary, pancreas, adrenal gland, testis and visceral adipose tissue. In addition, also heart, skeletal muscle, lung, liver and kidney showed autoradiographic signals. In the brain, strong (125)I-nesfatin 1 autoradiography was detected in the cortex, paraventricular nucleus of the hypothalamus, area postrema, dorsal motor nucleus of the vagus nerve and cerebellum. Based on the distribution of nesfatin-1 autoradiography, nesfatin-1 is a pleiotropic hormone that is involved in the regulation of several homeostatic functions. PMID- 26801558 TI - Cyclooxygenase-2 contributes to the selective induction of cell death by the endocannabinoid 2-arachidonoyl glycerol in hepatic stellate cells. AB - The endogenous cannabinoid 2-arachidonoyl glycerol (2-AG) is an anti-fibrotic lipid mediator that induces apoptosis in hepatic stellate cells (HSCs), but not in hepatocytes. However, the exact molecular mechanisms of this selective induction of HSC death are still unresolved. Interestingly, the inducible isoform of cyclooxygenase, COX-2, can metabolize 2-AG to pro-apoptotic prostaglandin glycerol esters (PG-GEs). We analyzed the roles of COX-2 and endocannabinoid derived PG-GEs in the differential susceptibility of primary activated HSCs and hepatocytes toward 2-AG-induced cell death. HSCs displayed significant COX-2 expression in contrast to hepatocytes. Similar to 2-AG, treatment of HSCs with PGD2-GE dose-dependently induced cell death independently from cannabinoid receptors that was accompanied by PARP- and caspase 3-cleavage. In contrast to 2 AG, PGD2-GE failed to induce significant ROS formation in HSCs, and depletion of membrane cholesterol did not rescue HSCs from PGD2-GE-induced apoptosis. These findings indicate differential engagement of initial intracellular signaling pathways by 2-AG and its COX-2-derived metabolite PGD2-GE, but similar final cell death pathways. Other PG-GEs, such as PGE2-or PGF2alpha-GE did not induce apoptosis in HSCs. Primary rat hepatocytes were mainly resistant against 2-AG- and PGD2-GE-induced apoptosis. HSCs, but not hepatocytes were able to metabolize 2-AG to PGD2-GE. As a proof of principle, HSCs from COX-2(-/-) mice lacked PDG2 GE production after 2-AG treatment. Accordingly, COX-2(-/-) HSCs were resistant against 2-AG-induced apoptosis. In conclusion, the divergent expression of COX-2 in HSCs and hepatocytes contributes to the different susceptibility of these cell types towards 2-AG-induced cell death due to the generation of pro-apoptotic PGD2 GE by COX-2 in HSCs. Modulation of COX-2-driven metabolization of 2-AG may provide a novel physiological concept allowing the specific targeting of HSCs in liver fibrosis. PMID- 26801559 TI - MiRNA-486 regulates angiogenic activity and survival of mesenchymal stem cells under hypoxia through modulating Akt signal. AB - MicroRNA-486 (miR-486) was first identified from human fetal liver cDNA library and validated as a regulator of hematopoiesis. Its roles in regulating the biological function of bone marrow-derived mesnechymal stem cells (BM-MSCs) under hypoxia have not been explored yet. In this study, we demonstrated that exposure to hypoxia upregulates miR-486 expression in BM-MSCs. Lentivirus-mediated overexpression of miR-486 resulted in increase of hepatocyte growth factor (HGF) and vascular endothelial growth factor(VEGF) in both mRNA and protein levels. MiR 486 expression also promotes proliferation and reduces apoptosis of BM-MSCs. Whereas MiR-486 knockdown downregulated the secretion of HGF and VEGF and induced apoptosis of BM-MSCs. Furthermore, PTEN-PI3K/AKT signaling was validated to be involved in changes of BM-MSC biological functions regulated by miR-486. These results suggested that MiR-486 mediated the hypoxia-induced angiogenic activity and promoted the proliferation and survival of BM-MSCs through regulating PTEN PI3K/AKT signaling. These findings might provide a novel understanding of effective therapeutic strategy for hypoxic-ischemic diseases. PMID- 26801560 TI - Ribosomal protein methyltransferases in the yeast Saccharomyces cerevisiae: Roles in ribosome biogenesis and translation. AB - A significant percentage of the methyltransferasome in Saccharomyces cerevisiae and higher eukaryotes is devoted to methylation of the translational machinery. Methylation of the RNA components of the translational machinery has been studied extensively and is important for structure stability, ribosome biogenesis, and translational fidelity. However, the functional effects of ribosomal protein methylation by their cognate methyltransferases are still largely unknown. Previous work has shown that the ribosomal protein Rpl3 methyltransferase, histidine protein methyltransferase 1 (Hpm1), is important for ribosome biogenesis and translation elongation fidelity. In this study, yeast strains deficient in each of the ten ribosomal protein methyltransferases in S. cerevisiae were examined for potential defects in ribosome biogenesis and translation. Like Hpm1-deficient cells, loss of four of the nine other ribosomal protein methyltransferases resulted in defects in ribosomal subunit synthesis. All of the mutant strains exhibited resistance to the ribosome inhibitors anisomycin and/or cycloheximide in plate assays, but not in liquid culture. Translational fidelity assays measuring stop codon readthrough, amino acid misincorporation, and programmed -1 ribosomal frameshifting, revealed that eight of the ten enzymes are important for translation elongation fidelity and the remaining two are necessary for translation termination efficiency. Altogether, these results demonstrate that ribosomal protein methyltransferases in S. cerevisiae play important roles in ribosome biogenesis and translation. PMID- 26801561 TI - TIEG1 enhances Osterix expression and mediates its induction by TGFbeta and BMP2 in osteoblasts. AB - Deletion of TIEG1/KLF10 in mice results in an osteopenic skeletal phenotype with significant decreases in both bone mineral density and content throughout the skeleton. Calvarial osteoblasts isolated from TIEG1 knockout (KO) mice display numerous changes in gene expression and exhibit significant delays in their mineralization rates relative to wild-type (WT) controls. Here, we demonstrate that loss of TIEG1 expression in osteoblasts results in decreased levels of Osterix mRNA. Suppression of TIEG1 expression in WT osteoblasts leads to decreased Osterix expression while restoration of TIEG1 expression in TIEG1 KO osteoblasts results in increased levels of Osterix. Transient transfection and chromatin immunoprecipitation assays reveal that TIEG1 directly binds to and activates the Osterix promoter and demonstrate that the zinc finger-containing DNA binding domain of TIEG1 is necessary for this regulation. Furthermore, we reveal that TIEG1 expression is essential for the induction of Osterix expression by important bone-related cytokines such as TGFbeta and BMP2 in osteoblast cells. Taken together, these data implicate an important role for TIEG1 in regulating the expression of Osterix, a master regulator of osteoblast differentiation and bone formation, and suggest that decreased expression of Osterix, as well as impaired TGFbeta and BMP2 signaling, contribute to the observed osteopenic bone phenotype of TIEG1 KO mice. PMID- 26801562 TI - Fork restart protein, PriA, binds around oriC after depletion of nucleotide precursors: Replication fork arrest near the replication origin. AB - Arrest of replication fork progression is one of the most common causes for increasing the genomic instability. In bacteria, PriA, a conserved DEXH-type helicase, plays a major role in recognition of the stalled forks and restart of DNA replication. We took advantage of PriA's ability to specifically recognize stalled replication forks to determine the genomic loci where replication forks are prone to stall on the Escherichia coli genome. We found that PriA binds around oriC upon thymine starvation which reduces the nucleotide supply and causes replication fork stalling. PriA binding quickly disappeared upon readdition of thymine. Furthermore, BrdU was incorporated at around oriC upon release from thymine starvation. Our results indicate that reduced supply of DNA replication precursors causes replication fork stalling preferentially in the 600 kb segment centered at oriC. This suggests that replication of the vicinity of oriC requires higher level of nucleotide precursors. The results also point to a possibility of slow fork movement and/or the presence of multiple fork arrest signals within this segment. Indeed, we have identified rather strong fork stall/pausing signals symmetrically located at ~50 kb away from oriC. We speculate that replication pausing and fork-slow-down shortly after initiation may represent a novel checkpoint that ensures the presence of sufficient nucleotide supply prior to commitment to duplication of the entire genome. PMID- 26801563 TI - Isolated human islets require hyperoxia to maintain islet mass, metabolism, and function. AB - Pancreatic islet transplantation has been recognized as an effective treatment for Type 1 diabetes; however, there is still plenty of room to improve transplantation efficiency. Because islets are metabolically active they require high oxygen to survive; thus hypoxia after transplant is one of the major causes of graft failure. Knowing the optimal oxygen tension for isolated islets would allow a transplant team to provide the best oxygen environment during pre- and post-transplant periods. To address this issue and begin to establish empirically determined guidelines for islet maintenance, we exposed in vitro cultured islets to different partial oxygen pressures (pO2) and assessed changes in islet volume, viability, metabolism, and function. Human islets were cultured for 7 days in different pO2 media corresponding to hypoxia (90 mmHg), normoxia (160 mmHg), and hyerpoxia (270 or 350 mmHg). Compared to normoxia and hypoxia, hyperoxia alleviated the loss of islet volume, maintaining higher islet viability and metabolism as measured by oxygen consumption and glucose-stimulated insulin secretion responses. We predict that maintaining pre- and post-transplanted islets in a hyperoxic environment will alleviate islet volume loss and maintain islet quality thereby improving transplant outcomes. PMID- 26801564 TI - Methylation of neurofilament light polypeptide promoter is associated with cell invasion and metastasis in NSCLC. AB - The role of NEFL in NSCLC remains largely unknown. Immunohistochemistry was performed to investigate the expression of NEFL in 108 lung cancer specimens. NEFL expression was associated with decreased lymph node metastases and favorable prognosis. Furthermore, real-time PCR and Western blot were used to investigate the expression of the NEFL gene in NSCLC cell lines. Subsequently, lentivirus mediated RNA interference and overexpression were used to demonstrate that knocked-down of NEFL enhanced the invasion and migration of A549 and H460 NSCLC cells, whereas NEFL overexpression resulted in a suppression of the invasion and migration of GLC-82 and L78 cells in vitro. In addition, bisulfite sequence PCR assay demonstrated that NEFL downregulation was associated with promoter methylation, and NEFL expression was restored after treatment with 5-Aza-dC. Finally, we demonstrated that NEFL inhibited the NF-kappaB pathway, thereby suppressing the expression of uPA and decreasing NSCLC invasiveness and migration. Our studies suggest that NEFL methylation is a novel mechanism for NSCLC invasion and metastasis and that NEFL may represent a candidate biomarker for recurrence and survival in patients with NSCLC. PMID- 26801565 TI - Gene expression profile of angiogenic factors in pulmonary arteries in COPD: relationship with vascular remodeling. AB - Pulmonary vessel remodeling in chronic obstructive pulmonary disease (COPD) involves changes in smooth muscle cell proliferation, which are highly dependent on the coordinated interaction of angiogenic-related growth factors. The purpose of the study was to investigate, in isolated pulmonary arteries (PA) from patients with COPD, the gene expression of 46 genes known to be modulators of the angiogenic process and/or involved in smooth muscle cell proliferation and to relate it to vascular remodeling. PA segments were isolated from 29 patients and classified into tertiles, according to intimal thickness. After RNA extraction, the gene expression was assessed by RT-PCR using TaqMan low-density arrays. The univariate analysis only showed upregulation of angiopoietin-2 (ANGPT-2) in remodeled PA (P < 0.05). The immunohistochemical expression of ANGPT-2 correlated with intimal enlargement (r = 0.42, P < 0.05). However, a combination of 10 factors in a multivariate discriminant analysis model explained up to 96% of the classification of the arteries. A network analysis of 46 genes showed major decentralization. In this network, the metalloproteinase-2 (MMP-2) was shown to be the bridge between intimal enlargement and fibrogenic factors. In COPD patients, plasma levels of ANGPT-2 were higher in current smokers or those with pulmonary hypertension. We conclude that an imbalance in ANGPT-2, combined with related factors such as VEGF, beta-catenin, and MMP-2, may partially explain the structural derangements of the arterial wall. MMP-2 may act as a bridge channeling actions from the main fibrogenic factors. PMID- 26801566 TI - gamma-Tocopherol supplementation of allergic female mice augments development of CD11c+CD11b+ dendritic cells in utero and allergic inflammation in neonates. AB - gamma-Tocopherol increases responses to allergen challenge in allergic adult mice, but it is not known whether gamma-tocopherol regulates the development of allergic disease. Development of allergic disease often occurs early in life. In clinical studies and animal models, offspring of allergic mothers have increased responsiveness to allergen challenge. Therefore, we determined whether gamma tocopherol augments development of allergic responses in offspring of allergic female mice. Allergic female mice were supplemented with gamma-tocopherol starting at mating. The pups from allergic mothers developed allergic lung responses, whereas pups from saline-treated mothers did not respond to allergen challenge. The gamma-tocopherol supplementation of allergic female mice increased the numbers of eosinophils twofold in the pup bronchoalveolar lavage and lungs after allergen challenge. There was also about a twofold increase in pup lung CD11b(+) subsets of CD11c(+) dendritic cells and in numbers of these dendritic cells expressing the transcription factor IRF4. There was no change in several CD11b(-) dendritic cell subsets. Furthermore, maternal supplementation with gamma tocopherol increased the number of fetal liver CD11b(+)CD11c(+) dendritic cells twofold in utero. In the pups, gamma-tocopherol increased lung expression of the inflammatory mediators CCL11, amphiregulin, activin A, and IL-5. In conclusion, maternal supplementation with gamma-tocopherol increased fetal development of subsets of dendritic cells that are critical for allergic responses and increased development of allergic responses in pups from allergic mothers. These results have implications for supplementation of allergic mothers with gamma-tocopherol in prenatal vitamins. PMID- 26801567 TI - Generation and functional characterization of epithelial cells with stable expression of SLC26A9 Cl- channels. AB - Recent studies identified the SLC26A9 Cl(-) channel as a modifier and potential therapeutic target in cystic fibrosis (CF). However, understanding of the regulation of SLC26A9 in epithelia remains limited and cellular models with stable expression for biochemical and functional studies are missing. We, therefore, generated Fisher rat thyroid (FRT) epithelial cells with stable expression of HA-tagged SLC26A9 via retroviral transfection and characterized SLC26A9 expression and function using Western blotting, immunolocalization, whole cell patch-clamp, and transepithelial bioelectric studies in Ussing chambers. We demonstrate stable expression of SLC26A9 in transfected FRT (SLC26A9-FRT) cells on the mRNA and protein level. Immunolocalization and Western blotting detected SLC26A9 in different intracellular compartments and to a lesser extent at the cell surface. Whole cell patch-clamp recordings demonstrated significantly increased constitutive Cl(-) currents in SLC26A9-FRT compared with control transduced FRT (Control-FRT) cells (P < 0.01). Similar, transepithelial measurements showed that the basal short circuit current was significantly increased in SLC26A9-FRT vs. Control-FRT cell monolayers (P < 0.01). SLC26A9 mediated Cl(-) currents were increased by cAMP-dependent stimulation (IBMX and forskolin) and inhibited by GlyH-101, niflumic acid, DIDS, and 5-nitro-2-(3 phenylpropylamino) benzoic acid (NPPB), as well as RNAi knockdown of WNK1 implicated in epithelial osmoregulation. Our results support that these novel epithelial cells with stable expression of SLC26A9 will be a useful model for studies of pharmacological regulation including the identification of activators of SLC26A9 Cl(-) channels that may compensate deficient cystic fibrosis transmembrane regulator (CFTR)-mediated Cl(-) secretion and serve as an alternative therapeutic target in patients with CF and potentially other muco obstructive lung diseases. PMID- 26801568 TI - Electrolyte transport properties in distal small airways from cystic fibrosis pigs with implications for host defense. AB - While pathological and clinical data suggest that small airways are involved in early cystic fibrosis (CF) lung disease development, little is known about how the lack of cystic fibrosis transmembrane conductance regulator (CFTR) function contributes to disease pathogenesis in these small airways. Large and small airway epithelia are exposed to different airflow velocities, temperatures, humidity, and CO2 concentrations. The cellular composition of these two regions is different, and small airways lack submucosal glands. To better understand the ion transport properties and impacts of lack of CFTR function on host defense function in small airways, we adapted a novel protocol to isolate small airway epithelial cells from CF and non-CF pigs and established an organotypic culture model. Compared with non-CF large airways, non-CF small airway epithelia cultures had higher Cl(-) and bicarbonate (HCO3 (-)) short-circuit currents and higher airway surface liquid (ASL) pH under 5% CO2 conditions. CF small airway epithelia were characterized by minimal Cl(-) and HCO3 (-) transport and decreased ASL pH, and had impaired bacterial killing compared with non-CF small airways. In addition, CF small airway epithelia had a higher ASL viscosity than non-CF small airways. Thus, the activity of CFTR is higher in the small airways, where it plays a role in alkalinization of ASL, enhancement of antimicrobial activity, and lowering of mucus viscosity. These data provide insight to explain why the small airways are a susceptible site for the bacterial colonization. PMID- 26801569 TI - Evidence of Apis cerana Sacbrood virus Infection in Apis mellifera. AB - Sacbrood virus(SBV) is one of the most destructive viruses in the Asian honeybee Apis cerana but is much less destructive in Apis mellifera In previous studies, SBV isolates infecting A. cerana(AcSBV) and SBV isolates infecting A. mellifera(AmSBV) were identified as different serotypes, suggesting a species barrier in SBV infection. In order to investigate this species isolation, we examined the presence of SBV infection in 318A. mellifera colonies and 64A. cerana colonies, and we identified the genotypes of SBV isolates. We also performed artificial infection experiments under both laboratory and field conditions. The results showed that 38A. mellifera colonies and 37A. cerana colonies were positive for SBV infection. Phylogenetic analysis based on RNA dependent RNA polymerase (RdRp) gene sequences indicated that A. cerana isolates and most A. mellifera isolates formed two distinct clades but two strains isolated fromA. mellifera were clustered with theA. cerana isolates. In the artificial-infection experiments, AcSBV negative-strand RNA could be detected in both adult bees and larvae ofA. mellifera, although there were no obvious signs of the disease, demonstrating the replication of AcSBV inA. mellifera Our results suggest that AcSBV is able to infectA. melliferacolonies with low prevalence (0.63% in this study) and pathogenicity. This work will help explain the different susceptibilities ofA. cerana and A. melliferato sacbrood disease and is potentially useful for guiding beekeeping practices. PMID- 26801570 TI - Comparative Toxicities of Salts on Microbial Processes in Soil. AB - Soil salinization is a growing threat to global agriculture and carbon sequestration, but to date it remains unclear how microbial processes will respond. We studied the acute response to salt exposure of a range of anabolic and catabolic microbial processes, including bacterial (leucine incorporation) and fungal (acetate incorporation into ergosterol) growth rates, respiration, and gross N mineralization and nitrification rates. To distinguish effects of specific ions from those of overall ionic strength, we compared the addition of four salts frequently associated with soil salinization (NaCl, KCl, Na2SO4, and K2SO4) to a nonsaline soil. To compare the tolerance of different microbial processes to salt and to interrelate the toxicity of different salts, concentration-response relationships were established. Growth-based measurements revealed that fungi were more resistant to salt exposure than bacteria. Effects by salt on C and N mineralization were indistinguishable, and in contrast to previous studies, nitrification was not found to be more sensitive to salt exposure than other microbial processes. The ion-specific toxicity of certain salts could be observed only for respiration, which was less inhibited by salts containing SO4(2-) than Cl(-) salts, in contrast to the microbial growth assessments. This suggested that the inhibition of microbial growth was explained solely by total ionic strength, while ion-specific toxicity also should be considered for effects on microbial decomposition. This difference resulted in an apparent reduction of microbial growth efficiency in response to exposure to SO4(2-) salts but not to Cl(-) salts; no evidence was found to distinguish K(+) and Na(+) salts. PMID- 26801571 TI - Molecular Structural Basis for the Cold Adaptedness of the Psychrophilic beta Glucosidase BglU in Micrococcus antarcticus. AB - Psychrophilic enzymes play crucial roles in cold adaptation of microbes and provide useful models for studies of protein evolution, folding, and dynamic properties. We examined the crystal structure (2.2-A resolution) of the psychrophilic beta-glucosidase BglU, a member of the glycosyl hydrolase 1 (GH1) enzyme family found in the cold-adapted bacterium Micrococcus antarcticus. Structural comparison and sequence alignment between BglU and its mesophilic and thermophilic counterpart enzymes (BglB and GlyTn, respectively) revealed two notable features distinct to BglU: (i) a unique long-loop L3 (35 versus 7 amino acids in others) involved in substrate binding and (ii) a unique amino acid, His299 (Tyr in others), involved in the stabilization of an ordered water molecule chain. Shortening of loop L3 to 25 amino acids reduced low-temperature catalytic activity, substrate-binding ability, the optimal temperature, and the melting temperature (Tm). Mutation of His299 to Tyr increased the optimal temperature, the Tm, and the catalytic activity. Conversely, mutation of Tyr301 to His in BglB caused a reduction in catalytic activity, thermostability, and the optimal temperature (45 to 35 degrees C). Loop L3 shortening and H299Y substitution jointly restored enzyme activity to the level of BglU, but at moderate temperatures. Our findings indicate that loop L3 controls the level of catalytic activity at low temperatures, residue His299 is responsible for thermolability (particularly heat lability of the active center), and long-loop L3 and His299 are jointly responsible for the psychrophilic properties. The described structural basis for the cold adaptedness of BglU will be helpful for structure-based engineering of new cold-adapted enzymes and for the production of mutants useful in a variety of industrial processes at different temperatures. PMID- 26801572 TI - Improvement of Biological Indicators by Uniformly Distributing Bacillus subtilis Spores in Monolayers To Evaluate Enhanced Spore Decontamination Technologies. AB - Novel decontamination technologies, including cold low-pressure plasma and blue light (400 nm), are promising alternatives to conventional surface decontamination methods. However, the standardization of the assessment of such sterilization processes remains to be accomplished. Bacterial endospores of the genera Bacillus and Geobacillus are frequently used as biological indicators (BIs) of sterility. Ensuring standardized and reproducible BIs for reliable testing procedures is a significant problem in industrial settings. In this study, an electrically driven spray deposition device was developed, allowing fast, reproducible, and homogeneous preparation of Bacillus subtilis 168 spore monolayers on glass surfaces. A detailed description of the structural design as well as the operating principle of the spraying device is given. The reproducible formation of spore monolayers of up to 5 * 10(7) spores per sample was verified by scanning electron microscopy. Surface inactivation studies revealed that monolayered spores were inactivated by UV-C (254 nm), low-pressure argon plasma (500 W, 10 Pa, 100 standard cubic cm per min), and blue light (400 nm) significantly faster than multilayered spores were. We have thus succeeded in the uniform preparation of reproducible, highly concentrated spore monolayers with the potential to generate BIs for a variety of nonpenetrating surface decontamination techniques. PMID- 26801573 TI - HupO, a Novel Regulator Involved in Thiosulfate-Responsive Control of HupSL [NiFe]-Hydrogenase Synthesis in Thiocapsa roseopersicina. AB - [NiFe]-hydrogenases are regulated by various factors to fulfill their physiological functions in bacterial cells. The photosynthetic purple sulfur bacterium Thiocapsa roseopersicina harbors four functional [NiFe]-hydrogenases: HynSL, HupSL, Hox1, and Hox2. Most of these hydrogenases are functionally linked to sulfur metabolism, and thiosulfate has a central role in this organism. The membrane-associated Hup hydrogenases have been shown to play a role in energy conservation through hydrogen recycling. The expression of Hup-type hydrogenases is regulated by H2 in Rhodobacter capsulatus and Cupriavidus necator; however, it has been shown that the corresponding hydrogen-sensing system is nonfunctional in T. roseopersicina and that thiosulfate is a regulating factor of hup expression. Here, we describe the discovery and analysis of mutants of a putative regulator (HupO) of the Hup hydrogenase in T. roseopersicina. HupO appears to mediate the transcriptional repression of Hup enzyme synthesis under low-thiosulfate conditions. We also demonstrate that the presence of the Hox1 hydrogenase strongly influences Hup enzyme synthesis in that hup expression was decreased significantly in the hox1 mutant. This reduction in Hup synthesis could be reversed by mutation of hupO, which resulted in strongly elevated hup expression, as well as Hup protein levels, and concomitant in vivo hydrogen uptake activity in the hox1 mutant. However, this regulatory control was observed only at low thiosulfate concentrations. Additionally, weak hydrogen-dependent hup expression was shown in the hupO mutant strain lacking the Hox1 hydrogenase. HupO-mediated Hup regulation therefore appears to link thiosulfate metabolism and the hydrogenase network in T. roseopersicina. PMID- 26801574 TI - Airborne Microalgae: Insights, Opportunities, and Challenges. AB - Airborne dispersal of microalgae has largely been a blind spot in environmental biological studies because of their low concentration in the atmosphere and the technical limitations in investigating microalgae from air samples. Recent studies show that airborne microalgae can survive air transportation and interact with the environment, possibly influencing their deposition rates. This minireview presents a summary of these studies and traces the possible route, step by step, from established ecosystems to new habitats through air transportation over a variety of geographic scales. Emission, transportation, deposition, and adaptation to atmospheric stress are discussed, as well as the consequences of their dispersal on health and the environment and state-of-the art techniques to detect and model airborne microalga dispersal. More-detailed studies on the microalga atmospheric cycle, including, for instance, ice nucleation activity and transport simulations, are crucial for improving our understanding of microalga ecology, identifying microalga interactions with the environment, and preventing unwanted contamination events or invasions. PMID- 26801575 TI - P212A Mutant of Dihydrodaidzein Reductase Enhances (S)-Equol Production and Enantioselectivity in a Recombinant Escherichia coli Whole-Cell Reaction System. AB - (S)-Equol, a gut bacterial isoflavone derivative, has drawn great attention because of its potent use for relieving female postmenopausal symptoms and preventing prostate cancer. Previous studies have reported on the dietary isoflavone metabolism of several human gut bacteria and the involved enzymes for conversion of daidzein to (S)-equol. However, the anaerobic growth conditions required by the gut bacteria and the low productivity and yield of (S)-equol limit its efficient production using only natural gut bacteria. In this study, the low (S)-equol biosynthesis of gut microorganisms was overcome by cloning the four enzymes involved in the biosynthesis from Slackia isoflavoniconvertens into Escherichia coli BL21(DE3). The reaction conditions were optimized for (S)-equol production from the recombinant strain, and this recombinant system enabled the efficient conversion of 200 MUM and 1 mM daidzein to (S)-equol under aerobic conditions, achieving yields of 95% and 85%, respectively. Since the biosynthesis of trans-tetrahydrodaidzein was found to be a rate-determining step for (S)-equol production, dihydrodaidzein reductase (DHDR) was subjected to rational site directed mutagenesis. The introduction of the DHDR P212A mutation increased the (S)-equol productivity from 59.0 mg/liter/h to 69.8 mg/liter/h in the whole-cell reaction. The P212A mutation caused an increase in the (S)-dihydrodaidzein enantioselectivity by decreasing the overall activity of DHDR, resulting in undetectable activity for (R)-dihydrodaidzein, such that a combination of the DHDR P212A mutant with dihydrodaidzein racemase enabled the production of (3S,4R) tetrahydrodaidzein with an enantioselectivity of >99%. PMID- 26801576 TI - Comparative Transcriptome Analysis of Vibrio splendidus JZ6 Reveals the Mechanism of Its Pathogenicity at Low Temperatures. AB - Yesso scallop-pathogenic Vibrio splendidus strain JZ6 was found to have the highest virulence at 10 degrees C, while its pathogenicity was significantly reduced with increased temperature and completely incapacitated at 28 degrees C. In the present study, comparative transcriptome analyses of JZ6 and another nonpathogenic V. splendidus strain, TZ19, were conducted at two crucial culture temperatures (10 degrees C and 28 degrees C) in order to determine the possible mechanism of temperature regulation of virulence. Comparisons among four libraries, constructed from JZ6 and TZ19 cultured at 10 degrees C and 28 degrees C (designated JZ6_10, JZ6_28, TZ19_10, and TZ19_28), revealed that 241 genes were possibly related to the increased virulence of JZ6 at 10 degrees C. There were 10 genes, including 2 encoding Flp pilus assembly proteins (FlhG and VS_2437), 6 encoding proteins of the "Vibrio cholerae pathogenic cycle" (ToxS, CqsA, CqsS, RpoS, HapR, and Vsm), and 2 encoding proteins in the Sec-dependent pathway (SecE and FtsY), that were significantly upregulated in JZ6_10 (P < 0.05) compared to those in JZ6_28, TZ19_10, and TZ19_28, which were supposed to be responsible for adhesion, quorum sensing, virulence, and protein secretion of V. splendidus. When cultured at 10 degrees C, JZ6 cells were larger and tended to aggregate more than those cultured at 28 degrees C. The virulence factor (extracellular metalloprotease) was also found to be highly expressed in the extracellular product (ECP) of JZ6 at 10 degrees C, and this ECP exhibited obvious cytotoxicity to oyster primary hemocytes, A549 cells, and L929 cells. These results indicated that low temperatures (10 degrees C) could enhance adhesion, activate the quorum sensing systems, upregulate virulence factor synthesis and secretion, and, lastly, increase the pathogenicity of JZ6. PMID- 26801577 TI - Novel Enzyme Family Found in Filamentous Fungi Catalyzing trans-4-Hydroxylation of L-Pipecolic Acid. AB - Hydroxypipecolic acids are bioactive compounds widely distributed in nature and are valuable building blocks for the organic synthesis of pharmaceuticals. We have found a novel hydroxylating enzyme with activity toward L-pipecolic acid (L Pip) in a filamentous fungus, Fusarium oxysporum c8D. The enzyme L-Pip trans-4 hydroxylase (Pip4H) of F. oxysporum (FoPip4H) belongs to the Fe(II)/alpha ketoglutarate-dependent dioxygenase superfamily, catalyzes the regio- and stereoselective hydroxylation of L-Pip, and produces optically pure trans-4 hydroxy-L-pipecolic acid (trans-4-L-HyPip). Amino acid sequence analysis revealed several fungal enzymes homologous with FoPip4H, and five of these also had L-Pip trans-4-hydroxylation activity. In particular, the homologous Pip4H enzyme derived from Aspergillus nidulans FGSC A4 (AnPip4H) had a broader substrate specificity spectrum than other homologues and reacted with the L and D forms of various cyclic and aliphatic amino acids. Using FoPip4H as a biocatalyst, a system for the preparative-scale production of chiral trans-4-L-HyPip was successfully developed. Thus, we report a fungal family of L-Pip hydroxylases and the enzymatic preparation of trans-4-L-HyPip, a bioactive compound and a constituent of secondary metabolites with useful physiological activities. PMID- 26801578 TI - Electroporation-Based Genetic Manipulation in Type I Methanotrophs. AB - Methane is becoming a major candidate for a prominent carbon feedstock in the future, and the bioconversion of methane into valuable products has drawn increasing attention. To facilitate the use of methanotrophic organisms as industrial strains and accelerate our ability to metabolically engineer methanotrophs, simple and rapid genetic tools are needed. Electroporation is one such enabling tool, but to date it has not been successful in a group of methanotrophs of interest for the production of chemicals and fuels, the gammaproteobacterial (type I) methanotrophs. In this study, we developed electroporation techniques with a high transformation efficiency for three different type I methanotrophs: Methylomicrobium buryatense 5GB1C, Methylomonas sp. strain LW13, and Methylobacter tundripaludum 21/22. We further developed this technique in M. buryatense, a haloalkaliphilic aerobic methanotroph that demonstrates robust growth with a high carbon conversion efficiency and is well suited for industrial use for the bioconversion of methane. On the basis of the high transformation efficiency of M. buryatense, gene knockouts or integration of a foreign fragment into the chromosome can be easily achieved by direct electroporation of PCR-generated deletion or integration constructs. Moreover, site-specific recombination (FLP-FRT [FLP recombination target] recombination) and sacB counterselection systems were employed to perform marker-free manipulation, and two new antibiotics, zeocin and hygromycin, were validated to be antibiotic markers in this strain. Together, these tools facilitate the rapid genetic manipulation of M. buryatense and other type I methanotrophs, promoting the ability to perform fundamental research and industrial process development with these strains. PMID- 26801579 TI - Reduced Glutathione Mediates Resistance to H2S Toxicity in Oral Streptococci. AB - Periodontal disease is associated with changes in the composition of the oral microflora, where health-associated oral streptococci decrease while Gram negative anaerobes predominate in disease. A key feature of periodontal disease associated anaerobes is their ability to produce hydrogen sulfide (H2S) abundantly as a by-product of anaerobic metabolism. So far, H2S has been reported to be either cytoprotective or cytotoxic by modulating bacterial antioxidant defense systems. Although oral anaerobes produce large amounts of H2S, the potential effects of H2S on oral streptococci are currently unknown. The aim of this study was to determine the effects of H2S on the survival and biofilm formation of oral streptococci. The growth and biofilm formation of Streptococcus mitis and Streptococcus oralis were inhibited by H2S. However, H2S did not significantly affect the growth of Streptococcus gordonii or Streptococcus sanguinis. The differential susceptibility of oral streptococci to H2S was attributed to differences in the intracellular concentrations of reduced glutathione (GSH). In the absence of GSH, H2S elicited its toxicity through an iron-dependent mechanism. Collectively, our results showed that H2S exerts antimicrobial effects on certain oral streptococci, potentially contributing to the decrease in health-associated plaque microflora. PMID- 26801580 TI - Evaluation of the Efficacy of Methyl Bromide in the Decontamination of Building and Interior Materials Contaminated with Bacillus anthracis Spores. AB - The primary goal of this study was to determine the conditions required for the effective inactivation of Bacillus anthracis spores on materials by using methyl bromide (MeBr) gas. Another objective was to obtain comparative decontamination efficacy data with three avirulent microorganisms to assess their potential for use as surrogates for B. anthracis Ames. Decontamination tests were conducted with spores of B. anthracis Ames and Geobacillus stearothermophilus, B. anthracis NNR1Delta1, and B. anthracis Sterne inoculated onto six different materials. Experimental variables included temperature, relative humidity (RH), MeBr concentration, and contact time. MeBr was found to be an effective decontaminant under a number of conditions. This study highlights the important role that RH has when fumigation is performed with MeBr. There were no tests in which a >=6 log10 reduction (LR) of B. anthracis Ames was achieved on all materials when fumigation was done at 45% RH. At 75% RH, an increase in the temperature, the MeBr concentration, or contact time generally improved the efficacy of fumigation with MeBr. This study provides new information for the effective use of MeBr at temperatures and RH levels lower than those that have been recommended previously. The study also provides data to assist with the selection of an avirulent surrogate for B. anthracis Ames spores when additional tests with MeBr are conducted. PMID- 26801581 TI - Individual variation and repeatability of corticosterone responses of little penguins (Eudyptula minor) sampled in two successive years at Oamaru, New Zealand. AB - Plasma corticosterone concentrations increase when birds experience a stressor, and plasma corticosterone responses to a capture and handling stressor have been measured in many species of birds. Whilst it is assumed that the reported corticosterone responses reflect the inherent sensitivity of each bird to the stressor, responses of the same birds have rarely been measured at intervals of one or more years. The current study was conducted to measure the repeatability in two successive years of corticosterone responses of little penguins (Eudyptula minor) at Oamaru, New Zealand. There was a wide range of individual corticosterone responses to capture and restraint in 96 little penguins in 2012 and 50 penguins sampled at the same time of year in 2013. There were significant repeatabilities for the ranks of corticosterone at 15, 30 and 60min (r=0.416+/ 0.160, r=0.636+/-0.115 and r=0.380+/-0.166 respectively) and for the ranks of integrated corticosterone responses (r=0.594+/-0.126) for 23 birds sampled in both years. There were no significant relationships between the size of corticosterone responses and age, body weight or condition index. Mean corticosterone concentrations at 60min were 114.22+/-6.65ng/ml in 2012 and 116.94+/-6.42ng/ml in 2013. Mean corticosterone responses did not differ between two successive years and were greater than responses of other penguin species. Penguins are well suited to long term studies in which corticosterone responses are measured annually as potential measures of changing marine environmental conditions. PMID- 26801582 TI - Thermogladius calderae gen. nov., sp. nov., an anaerobic, hyperthermophilic crenarchaeote from a Kamchatka hot spring. AB - An obligately anaerobic, hyperthermophilic, organoheterotrophic archaeon, strain 1633T, was isolated from a terrestrial hot spring of the Uzon Caldera (Kamchatka Peninsula, Russia). Cells were regular cocci, 0.5-0.9 MUm in diameter, with one flagellum. The temperature range for growth was 80-95 degrees C, with an optimum at 84 degrees C. Strain 1633T grew on yeast extract, beef extract, peptone, cellulose and cellobiose. No growth was detected on other sugars or carbohydrates, organic acids, or under autotrophic conditions. The only detected growth products were CO2, acetate, and H2. The growth rate was stimulated by elemental sulfur, which was reduced to hydrogen sulfide. The in silico-calculated G+C content of the genomic DNA of strain 1633T was 55.64 mol%. 16S rRNA gene sequence analysis placed strain 1633T together with the non-validly published 'Thermogladius shockii' strain WB1 in a separate genus-level cluster within the family Desulfurococcaceae. Average nucleotide identity (ANI) results revealed 75.72 % identity between strain 1633T and 'Thermogladius shockii' WB1. Based on these results we propose a novel genus and species with the name Thermogladius calderae gen. nov., sp. nov. The type strain of the type species is 1633T ( = DSM 22663T = VKM B-2946T). PMID- 26801583 TI - Silver Nanoparticle-Induced Autophagic-Lysosomal Disruption and NLRP3 Inflammasome Activation in HepG2 Cells Is Size-Dependent. AB - Silver nanoparticles (AgNPs) are incorporated into medical and consumer products to exploit their excellent antimicrobial properties; however, potential mechanisms of toxicity of AgNPs in mammalian cells are not fully understood. The objective of this study was to determine the mechanism of size- and concentration dependent cytotoxicity of AgNPs in human liver-derived hepatoma (HepG2) cells. Mechanisms of toxicity were explored at subcytotoxic concentrations (<=10 ug/ml AgNPs) and autophagy induction, lysosomal activity, inflammasome-dependent caspase-1 activation, and apoptosis were examined. Using enhanced dark-field light microscopy, hyperspectral imaging, electron microscopy, and energy dispersive X-ray spectroscopy, AgNPs were shown to rapidly accumulate in cytoplasmic vesicles for up to 24 h and 10-nm AgNPs exhibited the highest uptake and accumulation. Autophagy and enhanced lysosomal activity were induced at noncytotoxic concentrations (1 ug/ml; primary particle size:10 > 50 >100 nm), whereas increased caspase-3 activity (associated with apoptosis) was observed at cytotoxic concentrations (10, 25, and 50 ug/ml). Subcytotoxic concentrations of AgNPs enhanced expression of LC3B, a pro-autophagic protein, and CHOP, an apoptosis inducing ER-stress protein, and activation of NLRP3-inflammasome (caspase-1, IL-1beta). Disrupting the autophagy-lysosomal pathway through chloroquine or ATG5-siRNA exacerbated AgNPs-induced caspase-1 activation and lactate dehydrogenase release, suggesting that NLRP3-inflammasome plays an important role in AgNPs-induced cytotoxicity. Overall, 10-nm AgNPs showed the highest cellular responses compared with 50- and 100-nm AgNPs based on equal mass dosimetry. The results indicate the potential of vesicle-engulfed 10-nm AgNPs to induce cytotoxicity by a mechanism involving perturbations in the autophagy lysosomal system and inflammasome activation. PMID- 26801585 TI - Comprehensive geriatric assessment on an acute medical unit: a qualitative study of older people's and informal carer's perspectives of the care and treatment received. AB - OBJECTIVE: This qualitative study was imbedded in a randomized controlled trial evaluating the addition of geriatricians to usual care to enable the comprehensive geriatric assessment process with older patients on acute medical units. The qualitative study explored the perspectives of intervention participants on their care and treatment. DESIGN: A constructivist study incorporating semi-structured interviews that were conducted in patients' homes within six weeks of discharge from the acute medical unit. These interviews were recorded, transcribed, and analysed using thematic analysis. SETTING: An acute medical unit in the United Kingdom. PARTICIPANTS: Older patients ( n = 18) and their informal carers ( n = 6) discharged directly home from an acute medical unit, who had been in the intervention group of the randomized controlled trial. RESULTS: Three core themes were constructed: (1) perceived lack of treatment on the acute medical unit; (2) nebulous grasp of the role of the geriatrician; and (3) on-going health and activities of daily living needs postdischarge. These needs impacted upon the informal carers, who either took over, or helped the patients to complete their activities of daily living. Despite the help received with activities of daily living, a lot of the patients voiced a desire to complete these activities themselves. CONCLUSIONS: The participants perceived they were just monitored and observed on the acute medical unit, rather than receiving active treatment, and spoke of on-going unresolved health and activity of daily living needs following discharge, despite receiving the additional intervention of a geriatrician. PMID- 26801584 TI - MMP-9-Dependent Serum-Borne Bioactivity Caused by Multiwalled Carbon Nanotube Exposure Induces Vascular Dysfunction via the CD36 Scavenger Receptor. AB - Inhalation of multiwalled carbon nanotubes (MWCNT) causes systemic effects including vascular inflammation, endothelial dysfunction, and acute phase protein expression. MWCNTs translocate only minimally beyond the lungs, thus cardiovascular effects thereof may be caused by generation of secondary biomolecular factors from MWCNT-pulmonary interactions that spill over into the systemic circulation. Therefore, we hypothesized that induced matrix metalloproteinase-9 (MMP-9) is a generator of factors that, in turn, drive vascular effects through ligand-receptor interactions with the multiligand pattern recognition receptor, CD36. To test this, wildtype (WT; C57BL/6) and MMP 9(-/-)mice were exposed to varying doses (10 or 40 ug) of MWCNTs via oropharyngeal aspiration and serum was collected at 4 and 24 h postexposure. Endothelial cells treated with serum from MWCNT-exposed WT mice exhibited significantly reduced nitric oxide (NO) generation, as measured by electron paramagnetic resonance, an effect that was independent of NO scavenging. Serum from MWCNT-exposed WT mice inhibited acetylcholine (ACh)-mediated relaxation of aortic rings at both time points. Absence of CD36 on the aortic rings (obtained from CD36-deficient mice) abolished the serum-induced impairment of vasorelaxation. MWCNT exposure induced MMP-9 protein levels in both bronchoalveolar lavage and whole lung lysates. Serum from MMP-9(-/-)mice exposed to MWCNT did not diminish the magnitude of vasorelaxation in naive WT aortic rings, although a modest right shift of the ACh dose-response curve was observed in both MWCNT dose groups relative to controls. In conclusion, pulmonary exposure to MWCNT leads to elevated MMP-9 levels and MMP-9-dependent generation of circulating bioactive factors that promote endothelial dysfunction and decreased NO bioavailability via interaction with vascular CD36. PMID- 26801586 TI - Attenuation of a drug-sensitive strain of a turkey protozoan parasite Eimeria meleagrimitis by selection for precocious development. AB - An attenuated line of Eimeria meleagrimitis was established by repeated propagation of the parasite in 9-day old turkey poults and subsequent selection for precocious development. Following 20 passages, the prepatent period decreased from 120 to 104h. A series of experiments were conducted to evaluate the pathogenicity, immunogenicity and fecundity of the newly selected line. Judged by body weight gain, feed consumption and feed efficiency following infection, the attenuated line had appreciably reduced pathogenicity. Immunogenicity of the attenuated line was examined by infecting poults successively with incremental doses of 10(2), 10(3) and 10(4) oocysts at 0, 7, and 14 days of age respectively. No oocysts were detected following challenge with 5*10(2) oocysts, indicating that the attenuated line had retained immunogenicity. Fecundity was assessed by infecting two-week old birds with 5*10(2) oocysts of either parent or attenuated line. Oocyst production from 96 to 240h post-infection showed that the patent period of the attenuated line commenced earlier and was of shorter duration than the parent line. PMID- 26801587 TI - Lack of efficacy of monepantel against Trichostrongylus colubriformis in sheep in Brazil. AB - Multiple drug resistance of nematodes against anthelmintics has become one of the most important economic problems in sheep production worldwide. The aim of this experiment was to evaluate the efficacy of monepantel (2.5mg/kg) against gastrointestinal nematodes in fecal egg count reduction test (FECRT) and controlled efficacy test (CT) in naturally infected sheep. We used 30 sheep for the FECRT and 20 sheep for the CT, equally divided into control and treated groups. In the FECRT, the reduction was 98%. Larval identification of pre treatment coprocultures revealed 100% Haemonchus spp. for both control and treated groups. Post-treatment culture of treated sheep was 100% Oesophagostomum spp., but only few larvae were recovered. In the control group, they were 99% Haemonchus spp and 1% Oesophagostomum spp. larvae. Based on the FECRT, Haemonchus spp. was considered susceptible to monepantel. The efficacy of monepantel in the CT against Haemonchus contortus and Trichostrongylus axei was 100% and against Cooperia curticei was 99.7%. For Trichostrongylus colubriformis, the efficacy was -21.5%. In both treated and untreated animals, Oesophagostomum columbianum was recovered from the large intestines. Based on FECRT and CT and in accordance with WAAVP standards, monepantel was ineffective against T. colubriformis and O. columbianum, but effective against H. contortus, T. axei and C. curticei in the studied flock. PMID- 26801588 TI - Experimental Neospora caninum infection modifies trophoblast cell populations and plasma pregnancy-associated glycoprotein 1 and 2 dynamics in pregnant dairy heifers. AB - Neospora caninum is an obligate intracellular protozoan that causes abortion in cattle worldwide. Plasma concentrations of pregnancy-associated glycoprotein 1 (PAG-1), produced by binucleate trophoblast cells, are used for pregnancy diagnosis and as a marker of foetal-placental well-being, while PAG-2, produced by both mono- and binucleate trophoblast cells, may serve as an indicator of abortion risk. In prior work, natural N. caninum infection was found to modify plasma PAG-1 and PAG-2 patterns. The present study examines PAG-1 and PAG-2 dynamics and trophoblast cell populations following experimental infection with N. caninum. The study population was comprised of 17 N. caninum seronegative Holstein-Friesian heifers. On day 110 of gestation, 6 heifers were inoculated intravenously with 10(7) taquyzoites of N. canimum. Plasma samples for PAG-1 and PAG-2 determinations were collected on days 0, 7, 14, 21 and 42 post infection. During the study course, pregnancy was normally expressed in all controls while three infected heifers lost their foetuses. All heifers were euthanised on day 42 post infection and placentome samples from the 14 non-aborting heifers were collected to examine trophoblast cell populations. Plasma PAG-1 and PAG-2 concentrations in non-infected heifers increased until the day of euthanasia while non-aborting infected heifers showed a temporary fall in PAG-1 (P<0.004) and PAG-2 (P<0.002) concentrations from 7 to 14 days post infection (dpi). The two dams aborting at 14 and 21 dpi and a third dam with a mummified foetus upon euthanasia showed dramatic PAG-1 and PAG-2 reductions from 14 dpi to undetectable levels upon euthanasia. A stereological study of placentomes revealed significantly higher relative proportions of mono- (P=0.035) and binucleate (P=0.029) trophoblast cells at 42 dpi in non-infected heifers than infected non aborting heifers. According to our findings, following experimental N. caninum infection on day 110 of gestation, non-aborting heifers showed a brief reversible drop in plasma PAG-1 and 2 concentrations two weeks later and reduced proportions of bi- and mono-nucleate trophoblast cells 42 days after infection. In aborting dams, dramatically reduced PAG levels were related to severe placental damage and a non-viable pregnancy. PMID- 26801589 TI - Chagas disease in a Texan horse with neurologic deficits. AB - A 10-year-old Quarter Horse gelding presented to the Texas A&M University Veterinary Teaching Hospital with a six month-history of ataxia and lameness in the hind limbs. The horse was treated presumptively for equine protozoal myeloencephalitis (EPM) based on clinical signs but was ultimately euthanized after its condition worsened. Gross lesions were limited to a small area of reddening in the gray matter of the thoracic spinal cord. Histologically, trypanosome amastigotes morphologically similar to Trypanosoma cruzi, the agent of Chagas disease in humans and dogs, were sporadically detected within segments of the thoracic spinal cord surrounded by mild lymphoplasmacytic inflammation. Ancillary testing for Sarcocystis neurona, Neospora spp., Toxoplasma gondii and Leishmania spp. was negative. Conventional and real time polymerase chain reaction (PCR) of affected paraffin embedded spinal cord were positive for T. cruzi, and sequencing of the amplified T. cruzi satellite DNA PCR fragment from the horse was homologous with various clones of T. cruzi in GenBank. While canine Chagas disease cases have been widely reported in southern Texas, this is the first report of clinical T. cruzi infection in an equid with demonstrable amastigotes in the spinal cord. In contrast to previous instances of Chagas disease in the central nervous system (CNS) of dogs and humans, no inflammation or T. cruzi amastigotes were detected in the heart of the horse. Based on clinical signs, there is a potential for misdiagnosis of Chagas disease with other infectious diseases that affect the equine CNS. T. cruzi should be considered as a differential diagnosis in horses with neurologic clinical signs and histologic evidence of meningomyelitis that originate in areas where Chagas disease is present. The prevalence of T. cruzi in horses and the role of equids in the parasite life cycle require further study. PMID- 26801590 TI - Molecular epidemiology of Cryptosporidium species in livestock in Ireland. AB - Cryptosporidium is a protozoan that can cause gastro-intestinal illness with diarrhoea in a wide range of hosts. In fact some species of Cryptosporidium can infect the broad range of hosts. The current paper is focused to investigate monthly prevalence and diversity of Cryptosporidium spp. during the spring and early summer (March-June) in 2009 and 2010 in farms with no history of cryptosporidiosis. Animal samples were analyzed to elucidate the prevalence of Cryptosporidium in two regions, West and the East catchments in Ireland. Our investigation demonstrates the prevalence ranges from 14% to 26% an early summer peak (June) was observed. Based on the findings of this study Cryptosporidium ryanae (in cattle, horses), and Cryptosporidium bovis/xiaoi followed by Cryptosporidium parvum (in sheep) were found to be the predominant species in asymptomatic cases. The circulation of other Cryptosporidium species such as C. parvum, C. bovis, C. ubiquitum, C. andersoni and Cryptosporidium horse and pig genotypes in livestock was investigated. PMID- 26801591 TI - Immune-mediated responses account for the majority of production loss for grazing meat-breed lambs during Trichostrongylus colubriformis infection. AB - The hypothesis tested in this experiment was that Trichostrongylus colubriformis infection would reduce growth rates of grazing meat-breed lambs; however production loss would be reduced by suppression of the host immune response. The experiment had a 3*2 factorial design using 6-7 month old meat-breed lambs which remained uninfected or infected (IFY) with 2000 or 4000 T. colubriformis L3/week for 12 weeks and were immunosuppressed (SUPY) using methylprednisolone acetate once weekly or remained non-immunosuppressed (SUPN). Immunosuppression increased worm egg counts (WEC) of infected lambs (SUPY 2421 eggs per gram (epg), SUPN 1154 epg on day 84, p<0.05) and T. colubriformis burdens (p<0.05-0.10) and reduced circulating eosinophils (p<0.05 on days 11, 42, 56 and 84) and intestinal total antibody titres (p<0.02). There was a significant (p<0.05) interaction between the main effects of infection and immunosuppression with infection having a larger negative effect on the liveweight of non-immunosuppressed lambs. The immunological response of the host to T. colubriformis infection accounted for 75% of the overall cost of infection (3.1kg) with the majority of this cost occurring during the first 35 days of infection. In contrast, most of the cost associated with the direct effect of infection occurred after day 35. These results confirm in grazing meat-breed lambs that the host's immunological response to T. colubriformis infection is the major component of production loss. PMID- 26801592 TI - First report of the tick Hyalomma scupense (natural vector of bovine tropical theileriosis) on the French Mediterranean island of Corsica. AB - Hyalomma scupense (Acari, Ixodidae) is a common tick species found in several areas in North Africa, Asia and South Europe and an efficient natural vector of bovine tropical theileriosis (Theileria annulata), a livestock disease with an important economic impact. For one year, 1938 ticks were collected on cattle in several Corsican slaughterhouses; 168 of them were morphologically identified as H. scupense. This result was confirmed by genetic identification using sequences of mitochondrial cytochrome c oxidase subunit I (COI) and ribosomal internal transcribed spacer 2 (ITS2) genes. The presence of 2 different stages (adults and nymphs), collected in various areas of the island, indicates that a population of H. scupense is established in Corsica. However, bovine tropical theileriosis has not been diagnosed on the island so far. PMID- 26801593 TI - The utility of diversity profiling using Illumina 18S rRNA gene amplicon deep sequencing to detect and discriminate Toxoplasma gondii among the cyst-forming coccidia. AB - Next-generation sequencing (NGS) has the capacity to screen a single DNA sample and detect pathogen DNA from thousands of host DNA sequence reads, making it a versatile and informative tool for investigation of pathogens in diseased animals. The technique is effective and labor saving in the initial identification of pathogens, and will complement conventional diagnostic tests to associate the candidate pathogen with a disease process. In this report, we investigated the utility of the diversity profiling NGS approach using Illumina small subunit ribosomal RNA (18S rRNA) gene amplicon deep sequencing to detect Toxoplasma gondii in previously confirmed cases of toxoplasmosis. We then tested the diagnostic approach with species-specific PCR genotyping, histopathology and immunohistochemistry of toxoplasmosis in a Risso's dolphin (Grampus griseus) to systematically characterise the disease and associate causality. We show that the Euk7A/Euk570R primer set targeting the V1-V3 hypervariable region of the 18S rRNA gene can be used as a species-specific assay for cyst-forming coccidia and discriminate T. gondii. Overall, the approach is cost-effective and improves diagnostic decision support by narrowing the differential diagnosis list with more certainty than was previously possible. Furthermore, it supplements the limitations of cryptic protozoan morphology and surpasses the need for species specific PCR primer combinations. PMID- 26801594 TI - New findings of Enterocytozoon bieneusi in beef and dairy cattle in Brazil. AB - Microsporidia are widely recognized as important human pathogens with Enterocytozoon bieneusi as the most common species infecting humans and animals, including cattle. Although Brazil has the second largest cattle herd in the world and it is the largest exporter of beef there are no data on the presence or impact of E. bieneusi on this important population. To fill this knowledge gap, fecal specimens were collected from 452 cattle from pre-weaned calves to adult cattle in the state of Rio de Janeiro. Host factors including age, gender, dairy/beef, body composition, and fecal consistency were included in the study. Using molecular methods, E. bieneusi was found in 79/452 (17.5%) fecal specimens. This represents the first report of this parasite in Brazilian cattle. A significantly higher prevalence was found in calves less than 2 months of age (27.6%) and those 3-8 months of age (28.8%) versus heifers (14.1%) and adults (1.4%) (P<0.05). Dairy cattle (26.2%) had a higher prevalence than beef cattle (9.7%) (P<0.001). No correlation was found between infection and gender, body composition, and fecal consistency. Molecular characterization of the internal transcribed spacer (ITS) revealed 12 genotypes; five previously reported in cattle (BEB4, BEB8, D, EbpA and I), and seven novel genotypes (BEB11-BEB17). A phylogenetic analysis showed that 6 genotypes (D, EbpA, BEB12, BEB13, BEB15, and BEB16) identified in 18 animals clustered within the designated zoonotic Group 1 while the other 6 genotypes (I, BEB4, BEB8, BEB11, BEB14, BEB17) identified in 61 animals clustered within Group 2. The identification of genotypes in Brazilian cattle that have previously been reported in humans highlights the potential risk of zoonotic transmission and suggests that the role of cattle in transmission of human infections requires further study. PMID- 26801595 TI - Acute, fatal Sarcocystis calchasi-associated hepatitis in Roller pigeons (Columba livia f. dom.) at Philadelphia Zoo. AB - Four Roller pigeons (Columba livia f. dom.) at the Philadelphia Zoo died suddenly. Necropsy examination revealed macroscopic hepatitis. Microscopically, the predominant lesions were in liver, characterized with necrosis and mixed cell inflammatory response. Sarcocystis calchasi-like schizonts and free merozoites were identified in liver. Transmission electron microscopy confirmed that schizonts were in hepatocytes. A few schizonts were in spleen. PCR using S. calchasi-specific primers confirmed the diagnosis. Neither lesions nor protozoa were found in brain and muscles. This is the first report of acute visceral S. calchasi-associated sarcocystosis in naturally infected avian hosts. PMID- 26801596 TI - Semi-quantitative differentiation of cyathostomin larval cultures by reverse line blot. AB - Cyathostomins are the most prevalent horse nematodes worldwide and over 50 species are described. The eggs and the infective larvae (L3) can easily be obtained or cultured from infected horses, but cannot be differentiated morphologically at species level. A reverse line blot (RLB) method based on the hybridization of a PCR fragment with a species specific probe, has previously been developed for the differentiation of individual eggs and/or L3s, but is too labor intensive for large scale studies. In the present study a RLB method on multiple pooled L3s for the semi-quantitative differentiation of cyathostomin larval cultures was developed and validated. First, the probability of the presence of a certain species within a pool was calculated as function of the frequency and the number of L3s within a pool. Ten L3s per pool were found to be optimal. Next, the probability, the chance of occurrence was calculated when 4 pools per culture were used. The probability distributions for 0, 1, 2, 3 or 4 positive pools were transformed into the corresponding median frequency of the cumulative probability: 0.014, 0.04, 0.08, 0.16 and 0.59, respectively. Based on these calculated probabilities, RLB on 10 L3s per pool and 4 pools per sample was validated by estimating the cross-hybridization, precision and accuracy in 3 groups of horses. First, absence of cross-hybridization was confirmed by differentiation of the same L3s (160 L3s from the 4 horses from group 1) in the RLB on individual as well as on pooled L3s. Cross-hybridization was excluded for 9 of the most common cyathostomins. Next, the precision and accuracy were determined by the differentiation of 10 replicates of 3 cultures from 3 horses from group 2 (1200 L3s). The coefficient of variation (CV) was between 0 and 0.90 and the accuracy was between 0.42 and 1.73. A Monte Carlo simulation based on the observed scores and associated probability distributions gave similar results as the use of a fixed median frequency. The LPGs obtained from 276 larval culture counts from a larger cohort (23 horses, group 3) were not significantly different from the LPGs obtained from summation of the LPG per species found by RLB on pooled L3s. The RLB on pooled L3s was found therefore an useful semi-quantitative method for the differentiation of the most common cyathostomin L3, with a workload of approximately one tenth of that of the RLB on individual L3s. PMID- 26801597 TI - The impact of the climate on the epidemiology of Dirofilaria immitis in the pet population of the Canary Islands. AB - Cardiopulmonary dirofilariosis (heartworm) is a zoonotic vector borne disease caused by Dirofilaria immitis which affects domestic dogs and cats. Two of the seven Canary Islands are historically hyperendemic areas of dirofilariosis, although no epidemiological study has ever been carried out which includes the other islands. The aim of the study was to complete the epidemiological status of cardiopulmonary dirofilariosis in the canine and feline population throughout all the Canary Islands. 1643 client-owned dogs and 707 client-owned cats were tested for D. immitis antigens (dogs), and anti-D. immitis and anti-Wolbachia antibodies (cats). The prevalence of canine dirofilariosis in the Canary Islands was 15.7%, and the seroprevalence of feline dirofilariosis was 18.1%. A remarkable disparity was found when evaluating the results by island separately, which ranged from from 0% in Lanzarote and El Hierro, low prevalences and seroprevalences in Fuerteventura (1.8% and 2.5% in dogs and cats, respectively), to higher prevalences on the other 4 islands; ranging between 15.7% (dogs) and 14.3% (cats) in La Palma 22.5% (dogs) and 24.1% (cats) in Tenerife. In addition, prevalences and seroprevalences were very variable within each island, these differences being associated to local climate conditions. The distribution and prevalence of dirofilariosis in the Canary Islands is heterogeneous and related to climate, demographic factors and management of pets in the studied areas. Dirofilariosis remains hyperendemic in 4 of the 7 Islands. Since D. immitis is a zoonosis, veterinary and health authorities should be aware of the current prevalence and seroprevalence of animal dirofilariosis. The results show the need for awareness raising campaigns to promote the implementation of prophylactic measures in pets, in order to achieve a decrease in the prevalence of animal dirofilariosis in the Canary Islands. PMID- 26801598 TI - Liver fluke control on sheep farms in Northern Ireland: A survey of changing management practices in relation to disease prevalence and perceived triclabendazole resistance. AB - Reports of resistance to triclabendazole (TCBZ) among fluke populations have increased in recent years. Allied to this, there has been a rise in the prevalence of the disease, which has been linked to climate change. Results from questionnaire surveys conducted in Northern Ireland (NI) in 2005 (covering the years 1999-2004) and 2011 (covering the years 2008-2011) have provided an opportunity to examine the extent to which fluke control practices have changed over a prolonged time-frame, in light of these changes. A number of differences were highlighted. There was a significant shift away from the use of TCBZ over time, with it being replaced largely by closantel. The timing of treatments had moved earlier in the year, perhaps in response to climate change (and an altered pattern of disease). In relation to the frequency of drug treatments, there were no major changes in the overall pattern of drug treatments between the two survey points, although on both occasions approximately one-third of flock owners gave more than 3 treatments per year to ewes. In lowland areas in 2011, flock owners were rotating drug classes more often (each year and at each treatment) than in 2005, whereas in upland areas, flock owners were rotating less often and more were not rotating at all. Between 2005 and 2011, the percentage of flock owners giving quarantine treatments to bought-in stock had halved, to a very low level (approximately 10%). Using data from a complementary TCBZ resistance survey (Hanna et al., 2015), it has been shown that the way in which data are selected and which efficacy formula is applied can influence the calculation of drug efficiency and impact on diagnosis of resistance. PMID- 26801599 TI - Fasciola hepatica induces eosinophil apoptosis in the migratory and biliary stages of infection in sheep. AB - The aim of the present work was to evaluate the number of apoptotic eosinophils in the livers of sheep experimentally infected with Fasciola hepatica during the migratory and biliary stages of infection. Four groups (n=5) of sheep were used; groups 1-3 were orally infected with 200 metacercariae (mc) and sacrificed at 8 and 28 days post-infection (dpi), and 17 weeks post-infection (wpi), respectively. Group 4 was used as an uninfected control. Apoptosis was detected using immunohistochemistry with a polyclonal antibody against anti-active caspase 3, and transmission electron microscopy (TEM). Eosinophils were identified using the Hansel stain in serial sections for caspase-3, and by ultrastructural features using TEM. At 8 and 28 dpi, numerous caspase-3(+) eosinophils were mainly found at the periphery of acute hepatic necrotic foci. The percentage of caspase -3(+) apoptotic eosinophils in the periphery of necrotic foci was high (46.1-53.9) at 8 and 28 dpi, respectively, and decreased in granulomas found at 28 dpi (6%). Transmission electron microscopy confirmed the presence of apoptotic eosinophils in hepatic lesions at 8 and 28 dpi. At 17 wpi, apoptotic eosinophils were detected in the infiltrate surrounding some enlarged bile ducts containing adult flukes. This is the first report of apoptosis induced by F. hepatica in sheep and the first study reporting apoptosis in eosinophils in hepatic inflammatory infiltrates in vivo. The high number of apoptotic eosinophils in acute necrotic tracts during the migratory and biliary stages of infection suggests that eosinophil apoptosis may play a role in F. hepatica survival during different stages of infection. PMID- 26801600 TI - Population genetic structure of Ascaridia galli of extensively raised chickens of South Africa. AB - Ascaridia galli is one of the most common nematode affecting chickens. This study characterized A. galli parasites collected from South African village chickens of Limpopo (n=18) and KwaZulu-Natal (n=22) provinces using the 510bp sequences of cytochrome C oxidase subunit 1 gene of the mitochondrial DNA. Fourteen and 12 polymorphic sites were observed for Limpopo and KwaZulu-Natal sequences, respectively. Six haplotypes were observed in total. Haplotype diversity was high and ranged from 0.749 for Limpopo province to 0.758 for KwaZulu-Natal province isolates. There was no genetic differentiation between A. galli from Limpopo and KwaZulu-Natal provinces. The six South African haplotypes were unique compared to those published in the GeneBank sampled from Hy-line chickens raised under organic farming in Denmark. The utility of cytochrome C oxidase subunit 1 gene as a potential genetic marker for studying A. galli in village chicken populations is presented. PMID- 26801601 TI - Invitro acaricidal activity of ethnoveterinary plants and green synthesis of zinc oxide nanoparticles against Rhipicephalus (Boophilus) microplus. AB - The present study was designed to investigate the invitro acaricidal effects of seven ethnoveterinary plants, zinc acetate and green synthesized zinc oxide nanoparticles against the Southern cattle tick, Rhipicephalus (Boophilus) microplus. The selected ethnoveterinary plants were extracted using ethanol and aqueous (water) solvents at 0.02mg/ml and 0.04mg/ml concentrations. Of these seven plants, Lobelia leschenaultiana showed the highest percentage of tick mortality. The ethanol extracts of L. leschenaultiana showed 93.33% mortality at 0.04mg/ml and its LC50 was 0.05mg/ml. However, zinc acetate exhibited 70% mortality at 0.04mg/ml (LC50: 0.0192mg/ml). Further, we synthesized ZnO nanoparticle using the leaf extracts of L. leschenaultiana and zinc acetate as the precursor material to control R. (B.) microplus. The structural characterization of the synthesized ZnO nanoparticles (Ll-ZnO NPs) was performed by UV-vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and transmission electron microsopy (TEM). UV-vis spectra showed the absorption band at 383nm. XRD analysis clearly showed the crystalline nature of Ll-ZnO NPs with various Bragg's reflection peaks at 100, 002, 101, 102, 110, 103, 200, 201 and 202 planes. FTIR analysis showed the possible functional groups of Ll-ZnO NPs with strong band at 3420.63 and 2922.48cm(-1). SEM and TEM analysis revealed that the Ll-ZnO NPs were spherical and hexagonal in shape with particle size ranging between 20 and 65nm. The mortality of R. (B.) microplus after treatment with Ll-ZnO NPs was 35, 57.5 and 82.5% at 0.001, 0.002 and 0.004mg/ml. On the otherhand, 100% mortality of R. (B.) microplus was observed at 0.008mg/ml (LC50: 0.0017mg/ml). The results indicated that the Ll-ZnO NPs have good acaricidal properties compared to L. leschenaultiana leaf extract and zinc acetate. PMID- 26801602 TI - Naturally acquired bovine besnoitiosis: Differential distribution of parasites in the skin of chronically infected cattle. AB - Bovine besnoitiosis is caused by Besnoitia besnoiti, an apicomplexan parasite closely related to Toxoplasma gondii and Neospora caninum. In the acute stage of besnoitiosis, cattle suffer from pyrexia, swollen lymph nodes, anorexia and subcutaneous edema. In the chronic stage, tissue cysts are formed in a variety of tissues including the skin. Knowledge about the distribution of tissue cysts of different parts of the skin of infected animals is scarce. Four chronically infected cattle were euthanized and skin samples were taken from a total of 77 standardized cutaneous locations per animal. Portions of the dermis were taken, from which DNA was extracted and examined by real-time PCR. Cycle of transition (Ct) values reflecting the amount of parasite DNA in the samples were determined. For statistical analysis, samples were attributed to 11 larger skin regions ('OuterHindlegDistal', 'Rump, ForelegMiddle', 'NoseFrontEars', 'CheekEye', 'SideLowerPart', 'ForelegDistal', 'SideUpperPart', 'LegsInner', 'VentralHeadNeck', 'DorsalNeckWithersBackTail'). While all samples revealed a positive result in three female cattle, only 63.6% (49/77) of the samples of a bull showed positive results. For statistical analysis, a Ct value of 45 was assumed for samples with a negative result. The dams showed median Ct values of 16.1, 17.5 and 19.4, while in skin samples of the bull a median Ct value of 37.6 was observed. To determine the differences in DNA concentrations between different locations of the skin of the animals, a relative Ct (relCt) was determined by subtracting for each animal indv the MedianCtindv from each sample Ct. Analyses of the relCt values showed that the highest relative parasite DNA concentrations were observed in the categories 'OuterHindlegDistal', 'Rump', 'ForelegMiddle' and 'NoseFrontEars'. The relCt values in these categories differed statistically significantly from those determined for the categories 'VentralHeadNeck' and 'DorsalNeckWithersBackTail'. The analysis showed clear differences in the distribution and the detectability of parasite DNA in the skin of cattle infected with B. besnoiti. In all four animals, samples from the 'Rump' region (Regio fermoris) showed high parasite DNA concentrations. Because this region is also easily accessible for veterinarians, this skin location appears to be optimal for taking skin biopsies for detection or isolation of B. besnoiti. PMID- 26801603 TI - Multiple mutations in the acetylcholinesterase 3 gene associated with organophosphate resistance in Rhipicephalus (Boophilus) microplus ticks from Punjab, India. AB - The organophosphate (OP) resistance status in Rhipicephalus (Boophilus) microplus ticks collected from seventeen districts located in the northwestern Indian state, Punjab were characterized using three data sets (bioassay, biochemical and molecular assays). Adult immersion test (AIT) was adopted and the resistance factors (RF) for the field isolates were determined. Resistance to malathion was detected in 12 isolates among which 11 showed level I resistance status while level II status was recorded in one isolate (RF of 5.35). To understand the possible mechanism of resistance development, acetylcholinesterase (AChE) activity and gene sequences of the AChE3 were analyzed. A significantly (P<0.001) higher level of percent uninhibited AChE activity was recorded in all field isolates (36.36+/-0.46-43.77+/-1.21) in comparison to the susceptible population (29.39+/-0.40). The AChE activity was positively correlated with RF against malathion with a correlation coefficient (r) of 0.359. Analysis of nucleotides and their deduced amino acids sequences of partial AChE3 gene revealed the presence of six amino acid substitutions (I48L, I54V, V71A, I77M, S79P and R86Q). Three novel amino acid substitutions (V71A, I77M and S79P) in partial AChE3 gene were also identified in some of the isolates which may possibly have a role in OP resistance development. The PCR-RFLP assay with HaeIII revealed the presence of restriction site corresponding to R86Q mutation in all the field isolates along with an additional restriction site in seven field isolates corresponding to V71A mutation. The results of the study indicate the involvement of both insensitive AChE and higher percent uninhibited AChE activity as the possible mechanism in these field isolates. PMID- 26801604 TI - Cingulo-opercular network activity maintains alertness. AB - Previous investigations of alertness have confounded it with selective attention because targets were highly predictable. To truly isolate alertness we devised a sparse event-related design with many different randomly appearing and interleaved auditory and visual targets, thereby rendering prediction inefficient. Using functional magnetic resonance imaging, we then analyzed the influence of local brain activity variations prior to task appearance on reaction times, thus avoiding signal contributions from stimulus-driven attention. Higher pre-stimulus activity in a cingulo-opercular network, and the default mode network, resulted in faster response speed but only the former network showed task-positive responses. Conversely, dorsal attention network pre-stimulus activity was overall irrelevant and on auditory trials even detrimental to performance. Thus, in a paradigm where no information predicted timing, modality or properties of a subsequent stimulus, our results dissociate alertness, both anatomically and functionally, from attention and establish the central role of the cingulo-opercular network for sustaining alertness. PMID- 26801605 TI - Measurement of oxygen extraction fraction (OEF): An optimized BOLD signal model for use with hypercapnic and hyperoxic calibration. AB - Several techniques have been proposed to estimate relative changes in cerebral metabolic rate of oxygen consumption (CMRO2) by exploiting combined BOLD fMRI and cerebral blood flow data in conjunction with hypercapnic or hyperoxic respiratory challenges. More recently, methods based on respiratory challenges that include both hypercapnia and hyperoxia have been developed to assess absolute CMRO2, an important parameter for understanding brain energetics. In this paper, we empirically optimize a previously presented "original calibration model" relating BOLD and blood flow signals specifically for the estimation of oxygen extraction fraction (OEF) and absolute CMRO2. To do so, we have created a set of synthetic BOLD signals using a detailed BOLD signal model to reproduce experiments incorporating hypercapnic and hyperoxic respiratory challenges at 3T. A wide range of physiological conditions was simulated by varying input parameter values (baseline cerebral blood volume (CBV0), baseline cerebral blood flow (CBF0), baseline oxygen extraction fraction (OEF0) and hematocrit (Hct)). From the optimization of the calibration model for estimation of OEF and practical considerations of hypercapnic and hyperoxic respiratory challenges, a new "simplified calibration model" is established which reduces the complexity of the original calibration model by substituting the standard parameters alpha and beta with a single parameter theta. The optimal value of theta is determined (theta=0.06) across a range of experimental respiratory challenges. The simplified calibration model gives estimates of OEF0 and absolute CMRO2 closer to the true values used to simulate the experimental data compared to those estimated using the original model incorporating literature values of alpha and beta. Finally, an error propagation analysis demonstrates the susceptibility of the original and simplified calibration models to measurement errors and potential violations in the underlying assumptions of isometabolism. We conclude that using the simplified calibration model results in a reduced bias in OEF0 estimates across a wide range of potential respiratory challenge experimental designs. PMID- 26801606 TI - Sugar tax campaigners plea for action ahead of obesity strategy. PMID- 26801607 TI - Spatially heterogeneous populations with mixed negative and positive local density dependence. AB - Identifying the steady states of a population is a key issue in theoretical ecology, that includes the study of spatially heterogeneous populations. There are several examples of real ecosystems in patchy environments where the habitats are heterogeneous in their local density dependence. We investigate a multi-patch model of a single species with spatial dispersal, where the growth of the local population is logistic in some localities (negative density dependence) while other patches exhibit a strong Allee effect (positive density dependence). When the local dynamics is logistic in each patch and the habitats are interconnected by dispersal then the total population has only the extinction steady state and a componentwise positive equilibrium, corresponding to persistence in each patch. We show that animal populations in patchy environments can have a large number of steady states if local density dependence varies over the locations. It is demonstrated that, depending on the network topology of migration routes between the patches, the interaction of spatial dispersal and local density dependence can create a variety of coexisting stable positive equilibria. We give a detailed description of the multiple ways dispersal can rescue local populations from extinction. PMID- 26801608 TI - Long-term persisting hybrid swarm and geographic difference in hybridization pattern: genetic consequences of secondary contact between two Vincetoxicum species (Apocynaceae-Asclepiadoideae). AB - BACKGROUND: During glacial periods, glacial advances caused temperate plant extirpation or retreat into localized warmer areas, and subsequent postglacial glacial retreats resulted in range expansions, which facilitated secondary contact of previously allopatric isolated lineages. The evolutionary outcomes of secondary contact, including hybrid zones, dynamic hybrid swarm, and resultant hybrid speciation, depends on the strengths of reproductive barriers that have arisen through epistatic and pleiotropic effects during allopatric isolation. The aim of this study was to demonstrate refugia isolation and subsequent secondary contact between two perennial Asclepioid species and to assess the genetic consequences of the secondary contact. We modeled the range shift of two ecologically distinct Vincetoxicum species using the species distribution model (SDM) and assessed the genetic consequences of secondary contact by combining morphological and genetic approaches. We performed morphometric analysis (592 individuals) and examined 10 nuclear microsatellites (671 individuals) in V. atratum, V. japonicum, and putative hybrid populations. RESULTS: Multivariate analysis, model-based Bayesian analysis, and non-model-based discriminant analysis of principal components confirmed the hybridization between V. atratum and V. japonicum. High pollen fertility and a lack of linkage disequilibrium suggested that the hybrid populations may be self-sustaining and have persisted since V. atratum and V. japonicum came into contact during the post-glacial period. Moreover, our findings show that the pattern of hybridization between V. atratum and V. japonicum is unidirectional and differs among populations. Geographically-isolated hybrid populations exist as genetically distinct hybrid swarms that consist of V. atratum-like genotypes, V. japonicum-like genotypes, or admixed genotypes. In addition, Bayesian-based clustering analysis and coalescent based estimates of long-term gene flow showed patterns of introgressive hybridization in three morphologically 'pure' V. japonicum populations. CONCLUSION: In this study, we demonstrated that climatic oscillations during the Quaternary period likely led to species range shift and subsequently secondary contact. Hybrid populations may be self-sustaining and have persisted since V. atratum and V. japonicum came into contact during the post-glacial period. Pattern of hybridization between V. atratum and V. japonicum is unidirectional and differs among populations. We concluded that these differences in the genetic consequences of secondary contact are caused by historical colonization processes and/or natural selection. PMID- 26801609 TI - Evidence bicycle helmets mitigate intra-cranial injury is not controversial. PMID- 26801610 TI - The Arabidopsis AtPP2CA Protein Phosphatase Inhibits the GORK K+ Efflux Channel and Exerts a Dominant Suppressive Effect on Phosphomimetic-activating Mutations. AB - The regulation of the GORK (Guard Cell Outward Rectifying) Shaker channel mediating a massive K(+) efflux in Arabidopsis guard cells by the phosphatase AtPP2CA was investigated. Unlike the gork mutant, the atpp2ca mutants displayed a phenotype of reduced transpiration. We found that AtPP2CA interacts physically with GORK and inhibits GORK activity in Xenopus oocytes. Several amino acid substitutions in the AtPP2CA active site, including the dominant interfering G145D mutation, disrupted the GORK-AtPP2CA interaction, meaning that the native conformation of the AtPP2CA active site is required for the GORK-AtPP2CA interaction. Furthermore, two serines in the GORK ankyrin domain that mimic phosphorylation (Ser to Glu) or dephosphorylation (Ser to Ala) were mutated. Mutations mimicking phosphorylation led to a significant increase in GORK activity, whereas mutations mimicking dephosphorylation had no effect on GORK. In Xenopus oocytes, the interaction of AtPP2CA with "phosphorylated" or "dephosphorylated" GORK systematically led to inhibition of the channel to the same baseline level. Single-channel recordings indicated that the GORK S722E mutation increases the open probability of the channel in the absence, but not in the presence, of AtPP2CA. The dephosphorylation-independent inactivation mechanism of GORK by AtPP2CA is discussed in relation with well known conformational changes in animal Shaker-like channels that lead to channel opening and closing. In plants, PP2C activity would control the stomatal aperture by regulating both GORK and SLAC1, the two main channels required for stomatal closure. PMID- 26801611 TI - Expression of N-Acetylglucosaminyltransferase III Suppresses alpha2,3 Sialylation, and Its Distinctive Functions in Cell Migration Are Attributed to alpha2,6-Sialylation Levels. AB - N-Acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of the bisecting GlcNAc branch on N-glycans, is usually described as a metastasis suppressor. Overexpression of GnT-III inhibited migration in multiple types of tumor cells. However, these results seem controversial to the clinical observations for the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers. Here, we present evidence that these inconsistencies are mainly attributed to the different expression pattern of cell sialylation. In detail, we show that overexpression of GnT-III significantly inhibits alpha2,3 sialylation but not alpha2,6-sialylation. The migratory ability of cells without or with a low level of alpha2,6-sialylation is consistently suppressed after GnT III overexpression. In contrast, the effects of GnT-III overexpression are variable in tumor cells that are highly alpha2,6-sialylated. Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. Interestingly, up-regulation of alpha2,6 sialylation by overexpressing beta-galactoside alpha2,6-sialyltranferase 1 in the alpha2,6-hyposialylated HeLa-S3 cells abolishes the anti-migratory effects of GnT III. Conversely, depletion of alpha2,6-sialylation by knock-out of beta galactoside alpha2,6-sialyltranferase 1 in alpha2,6-hypersialylated HepG2 cells endows GnT-III with the anti-migratory ability. Taken together, our data clearly demonstrate that high expression of alpha2,6-sialylation on the cell surface could affect the anti-migratory role of GnT-III, which provides an insight into the mechanistic roles of GnT-III in tumor metastasis. PMID- 26801612 TI - MicroRNA-7 Regulates the Function of Mitochondrial Permeability Transition Pore by Targeting VDAC1 Expression. AB - Mitochondrial dysfunction is one of the major contributors to neurodegenerative disorders including Parkinson disease. The mitochondrial permeability transition pore is a protein complex located on the mitochondrial membrane. Under cellular stress, the pore opens, increasing the release of pro-apoptotic proteins, and ultimately resulting in cell death. MicroRNA-7 (miR-7) is a small non-coding RNA that has been found to exhibit a protective role in the cellular models of Parkinson disease. In the present study, miR-7 was predicted to regulate the function of mitochondria, according to gene ontology analysis of proteins that are down-regulated by miR-7. Indeed, miR-7 overexpression inhibited mitochondrial fragmentation, mitochondrial depolarization, cytochrome c release, reactive oxygen species generation, and release of mitochondrial calcium in response to 1 methyl-4-phenylpyridinium (MPP(+)) in human neuroblastoma SH-SY5Y cells. In addition, several of these findings were confirmed in mouse primary neurons. Among the mitochondrial proteins identified by gene ontology analysis, the expression of voltage-dependent anion channel 1 (VDAC1), a constituent of the mitochondrial permeability transition pore, was down-regulated by miR-7 through targeting 3'-untranslated region of VDAC1 mRNA. Similar to miR-7 overexpression, knockdown of VDAC1 also led to a decrease in intracellular reactive oxygen species generation and subsequent cellular protection against MPP(+). Notably, overexpression of VDAC1 without the 3'-UTR significantly abolished the protective effects of miR-7 against MPP(+)-induced cytotoxicity and mitochondrial dysfunction, suggesting that the protective effect of miR-7 is partly exerted through promoting mitochondrial function by targeting VDAC1 expression. These findings point to a novel mechanism by which miR-7 accomplishes neuroprotection by improving mitochondrial health. PMID- 26801613 TI - The Contribution of Non-catalytic Carbohydrate Binding Modules to the Activity of Lytic Polysaccharide Monooxygenases. AB - Lignocellulosic biomass is a sustainable industrial substrate. Copper-dependent lytic polysaccharide monooxygenases (LPMOs) contribute to the degradation of lignocellulose and increase the efficiency of biofuel production. LPMOs can contain non-catalytic carbohydrate binding modules (CBMs), but their role in the activity of these enzymes is poorly understood. Here we explored the importance of CBMs in LPMO function. The family 2a CBMs of two monooxygenases,CfLPMO10 andTbLPMO10 fromCellulomonas fimiandThermobispora bispora, respectively, were deleted and/or replaced with CBMs from other proteins. The data showed that the CBMs could potentiate and, surprisingly, inhibit LPMO activity, and that these effects were both enzyme-specific and substrate-specific. Removing the natural CBM or introducingCtCBM3a, from theClostridium thermocellumcellulosome scaffoldin CipA, almost abolished the catalytic activity of the LPMOs against the cellulosic substrates. The deleterious effect of CBM removal likely reflects the importance of prolonged presentation of the enzyme on the surface of the substrate for efficient catalytic activity, as only LPMOs appended to CBMs bound tightly to cellulose. The negative impact ofCtCBM3a is in sharp contrast with the capacity of this binding module to potentiate the activity of a range of glycoside hydrolases including cellulases. The deletion of the endogenous CBM fromCfLPMO10 or the introduction of a family 10 CBM fromCellvibrio japonicusLPMO10B intoTbLPMO10 influenced the quantity of non-oxidized products generated, demonstrating that CBMs can modulate the mode of action of LPMOs. This study demonstrates that engineered LPMO-CBM hybrids can display enhanced industrially relevant oxygenations. PMID- 26801614 TI - Myeloid Acyl-CoA:Cholesterol Acyltransferase 1 Deficiency Reduces Lesion Macrophage Content and Suppresses Atherosclerosis Progression. AB - Acyl-CoA:cholesterol acyltransferase 1 (Acat1) converts cellular cholesterol to cholesteryl esters and is considered a drug target for treating atherosclerosis. However, in mouse models for atherosclerosis, global Acat1 knockout (Acat1(-/-)) did not prevent lesion development. Acat1(-/-) increased apoptosis within lesions and led to several additional undesirable phenotypes, including hair loss, dry eye, leukocytosis, xanthomatosis, and a reduced life span. To determine the roles of Acat1 in monocytes/macrophages in atherosclerosis, we produced a myeloid specific Acat1 knockout (Acat1(-M/-M)) mouse and showed that, in the Apoe knockout (Apoe(-/-)) mouse model for atherosclerosis, Acat1(-M/-M) decreased the plaque area and reduced lesion size without causing leukocytosis, dry eye, hair loss, or a reduced life span. Acat1(-M/-M) enhanced xanthomatosis in apoe(-/-) mice, a skin disease that is not associated with diet-induced atherosclerosis in humans. Analyses of atherosclerotic lesions showed that Acat1(-M/-M) reduced macrophage numbers and diminished the cholesterol and cholesteryl ester load without causing detectable apoptotic cell death. Leukocyte migration analysis in vivo showed that Acat1(-M/-M) caused much fewer leukocytes to appear at the activated endothelium. Studies in inflammatory (Ly6C(hi)-positive) monocytes and in cultured macrophages showed that inhibiting ACAT1 by gene knockout or by pharmacological inhibition caused a significant decrease in integrin beta 1 (CD29) expression in activated monocytes/macrophages. The sparse presence of lesion macrophages without Acat1 can therefore, in part, be attributed to decreased interaction between inflammatory monocytes/macrophages lacking Acat1 and the activated endothelium. We conclude that targeting ACAT1 in a myeloid cell lineage suppresses atherosclerosis progression while avoiding many of the undesirable side effects caused by global Acat1 inhibition. PMID- 26801615 TI - Nutrient-regulated Phosphorylation of ATG13 Inhibits Starvation-induced Autophagy. AB - Autophagy is a conserved catabolic process that utilizes a defined series of membrane trafficking events to generate a de novo double-membrane vesicle termed the autophagosome, which matures by fusing to the lysosome. Subsequently, the lysosome facilitates the degradation and recycling of the cytoplasmic cargo. In yeast, the upstream signals that regulate the induction of starvation-induced autophagy are clearly defined. The nutrient-sensing kinase Tor inhibits the activation of autophagy by regulating the formation of the Atg1-Atg13-Atg17 complex, through hyperphosphorylation of Atg13. However, in mammals, the ortholog complex ULK1-ATG13-FIP200 is constitutively formed. As such, the molecular mechanism by which mTOR regulates mammalian autophagy is unknown. Here we report the identification and characterization of novel nutrient-regulated phosphorylation sites on ATG13: Ser-224 and Ser-258. mTOR directly phosphorylates ATG13 on Ser-258 while Ser-224 is modulated by the AMPK pathway. In ATG13 knock out cells reconstituted with an unphosphorylatable mutant of ATG13, ULK1 kinase activity is more potent, and amino acid starvation induced more rapid ATG13 and ULK1 translocation. These events culminated in a more rapid starvation-induced autophagy response. Therefore, ATG13 phosphorylation plays a crucial role in autophagy regulation. PMID- 26801616 TI - Comparison of the toxicities, activities and chemical profiles of raw and processed Xanthii Fructus. AB - BACKGROUND: Although toxic, the Chinese medicinal herb Xanthii Fructus (XF) is commonly used to treat traditional Chinese medicine (TCM) symptoms that resemble cold, sinusitis and arthritis. According to TCM theory, stir-baking (a processing method) can reduce the toxicity and enhance the efficacy of XF. METHODS: Cytotoxicities of raw XF and processed XF (stir-baked XF, SBXF) were determined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay in normal liver derived MIHA cells. Nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) mRNA expression were measured by the Griess reagent and quantitative real-time PCR, respectively. The chemical profiles of XF and SBXF were compared using an established ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method. RESULTS: SBXF was less toxic than XF in MIHA cells. Both XF and SBXF had anti-inflammatory effects as demonstrated by their abilities to reduce nitric oxide production as well as inducible nitric oxide synthase mRNA expression in lipopolysaccharide-stimulated RAW 264.7 macrophages. Interestingly, the anti inflammatory effects of SBXF were more potent than that of XF. By comparing the chemical profiles, we found that seven peaks were lower, while nine other peaks were higher in SBXF than in XF. Eleven compounds including carboxyatractyloside, atractyloside and chlorogenic acid corresponding to eleven individual changed peaks were tentatively identified by matching with empirical molecular formulae and mass fragments, as well as literature data. CONCLUSION: Our study showed that stir-baking significantly reduced the cytotoxicity and enhanced the anti inflammatory effects of XF; moreover, with a developed ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry method we differentiated XF and SBXF by their chemical profiles. Further studies are warranted to establish the relationship between the alteration of chemical profiles and the changes of medicinal properties caused by stir-baking. PMID- 26801618 TI - Evaluation of penetrating cardiac stab wounds. AB - BACKGROUND: The purpose of this study was to identify factors associated with unfavourable outcome following stab wounds to the heart in order to improve selection of patients who may benefit from resuscitative effort. METHODS: From February to March, variables were collected from medical records of patients sustaining cardiac trauma. The inclusion criterion was the presence of a penetrating cardiac injury confirmed intraoperatively. RESULTS: Ninety-eight patients were admitted with penetrating cardiac injury. The mortality rate was 60 %. Fifty-seven patients had unrecordable blood pressure at admission and emergency department thoracotomy was done in twelve patients. The AAST-OIS score was higher in non survivors group (4,21 vs 4,49). Multivariate analysis identified tamponade, associated injuries, right ventricular laceration as the most predictive variables for mortality. DISCUSSION: Stab wounds should be separated from gunshots wounds as the former mechanism has different pathophysiological issue. Patients arriving without signs of life may benefit from aggressive resuscitative efforts depending on transport time. CONCLUSION: Penetrating cardiac injuries are highly lethal condition. Cardiac tamponade, right ventricle lacerations and associated extra-cardiac injuries are independent risk factors of death. PMID- 26801617 TI - Obesity and colorectal cancer: molecular features of adipose tissue. AB - The huge part of population in developed countries is overweight or obese. Obesity is often determined by body mass index (BMI) but new accurate methods and ratios have recently appeared to measure body fat or fat located in the intestines. Early diagnosis of obesity is crucial since it is considered an increasing colorectal cancer risk factor. On the one hand, colorectal cancer has been strongly associated with lifestyle factors. A diet rich in red and processed meats may increase colorectal cancer risk; however, high-fiber diets (grains, cereals and fruits) have been associated with a decreased risk of colorectal cancer. Other life-style factors associated with obesity that also increase colorectal cancer risk are physical inactivity, smoking and high alcohol intake. Cutting-edge studies reported that high-risk transformation ability of adipose tissue is due to production of different pro-inflammatory cytokines like IL-8, IL 6 or IL-2 and other enzymes like lactate dehydrogenase (LDH) and tumour necrosis factor alpha (TNFalpha). Furthermore, oxidative stress produces fatty-acid peroxidation whose metabolites possess very high toxicities and mutagenic properties. 4-hydroxy-2-nonenal (4-HNE) is an active compounds that upregulates prostaglandin E2 which is directly associated with high proliferative colorectal cancer. Moreover, 4-HNE deregulates cell proliferation, cell survival, differentiation, autophagy, senescence, apoptosis and necrosis via mitogen activated protein kinase (MAPK), phosphoinositide 3-kinase (PIK3CA)-AKT and protein kinase C pathways. Other product of lipid peroxidation is malondialdehyde (MDA) being able to regulate insulin through WNT-pathway as well as having demonstrated its mutagenic capability. Accumulation of point mutation enables genomic evolution of colorectal cancer described in the model of Fearon and Vogelstein. In this review, we will summarize different determination methods and techniques to assess a truthfully diagnosis and we will explain some of the capabilities that performs adipocytes as the largest endocrine organ. PMID- 26801619 TI - Effectiveness of interventions to directly support food and drink intake in people with dementia: systematic review and meta-analysis. AB - BACKGROUND: Eating and drinking difficulties are recognised sources of ill health in people with dementia. In the EDWINA (Eating and Drinking Well IN dementiA) systematic review we aimed to assess effectiveness of interventions to directly improve, maintain or facilitate oral food and drink intake, nutrition and hydration status, in people with cognitive impairment or dementia (across all settings, levels of care and support, types and degrees of dementia). Interventions included oral nutrition supplementation, food modification, dysphagia management, eating assistance and supporting the social element of eating and drinking. METHODS: We comprehensively searched 13 databases for relevant intervention studies. The review was conducted with service user input in accordance with Cochrane Collaboration's guidelines. We duplicated assessment of inclusion, data extraction, and validity assessment, tabulating data, carrying out random effects meta-analysis and narrative synthesis. RESULTS: Forty-three controlled interventions were included, disappointingly none were judged at low risk of bias. Oral nutritional supplementation studies suggested small positive short term but unclear long term effects on nutritional status. Food modification or dysphagia management studies were smaller and of low quality, providing little evidence of an improved nutritional status. Eating assistance studies provided inconsistent evidence, but studies with a strong social element around eating/drinking, although small and of low quality provided consistent suggestion of improvements in aspects of quality of life. There were few data to address stakeholders' questions. CONCLUSIONS: We found no definitive evidence on effectiveness, or lack of effectiveness, of specific interventions but studies were small and short term. People with cognitive impairment and their carers have to tackle eating problems despite this lack of evidence, so promising interventions are listed. The need remains for high quality trials tailored for people with cognitive impairment assessing robust outcomes. SYSTEMATIC REVIEW REGISTRATION: The systematic review protocol was registered (CRD42014007611) and is published, with the full MEDLINE search strategy, on Prospero. PMID- 26801620 TI - Evaluation of the effects of the Arm Light Exoskeleton on movement execution and muscle activities: a pilot study on healthy subjects. AB - BACKGROUND: Exoskeletons for lower and upper extremities have been introduced in neurorehabilitation because they can guide the patient's limb following its anatomy, covering many degrees of freedom and most of its natural workspace, and allowing the control of the articular joints. The aims of this study were to evaluate the possible use of a novel exoskeleton, the Arm Light Exoskeleton (ALEx), for robot-aided neurorehabilitation and to investigate the effects of some rehabilitative strategies adopted in robot-assisted training. METHODS: We studied movement execution and muscle activities of 16 upper limb muscles in six healthy subjects, focusing on end-effector and joint kinematics, muscle synergies, and spinal maps. The subjects performed three dimensional point-to point reaching movements, without and with the exoskeleton in different assistive modalities and control strategies. RESULTS: The results showed that ALEx supported the upper limb in all modalities and control strategies: it reduced the muscular activity of the shoulder's abductors and it increased the activity of the elbow flexors. The different assistive modalities favored kinematics and muscle coordination similar to natural movements, but the muscle activity during the movements assisted by the exoskeleton was reduced with respect to the movements actively performed by the subjects. Moreover, natural trajectories recorded from the movements actively performed by the subjects seemed to promote an activity of muscles and spinal circuitries more similar to the natural one. CONCLUSIONS: The preliminary analysis on healthy subjects supported the use of ALEx for post-stroke upper limb robotic assisted rehabilitation, and it provided clues on the effects of different rehabilitative strategies on movement and muscle coordination. PMID- 26801621 TI - Identification of valid reference genes for microRNA expression studies in a hepatitis B virus replicating liver cell line. AB - BACKGROUND: MicroRNAs are regulatory molecules and suggested as non-invasive biomarkers for molecular diagnostics and prognostics. Altered expression levels of specific microRNAs are associated with hepatitis B virus infection and hepatocellular carcinoma. We previously identified differentially expressed microRNAs with liver-specific target genes in plasma from children with chronic hepatitis B. To further understand the biological role of these microRNAs in the pathogenesis of chronic hepatitis B, we have used the human liver cell line HepG2, with and without HBV replication, after transfection of hepatitis B virus expression vectors. RT-qPCR is the preferred method for microRNA studies, and a careful normalisation strategy, verifying the optimal set of reference genes, is decisive for correctly evaluating microRNA expression levels. The aim of this study was to provide valid reference genes for the human HCC-derived cell line HepG2. RESULTS: A panel of 739 microRNAs was screened to identify the most stably expressed microRNAs, followed by a PubMed search identifying microRNAs previously used as reference genes. Sixteen candidate reference genes were validated by RT qPCR. Reference gene stabilities were calculated first by standard deviations of DeltaCt values and then by geNorm and NormFinder analyses, taking into account the amplification efficiency of each microRNA primer set. The optimal set of reference genes was verified by a target analysis using RT-qPCR on miR-215-5p. CONCLUSION: We identified miR-24-3p, miR-151a-5p, and miR-425-5p as the most valid combination of reference genes for microRNA RT-qPCR studies in our hepatitis B virus replicating HepG2 cell model. PMID- 26801622 TI - Factors influencing mother's participation in Posyandu for improving nutritional status of children under-five in Aceh Utara district, Aceh province, Indonesia. AB - BACKGROUND: Posyandu, or pos pelayanan terpadu (integrated service post), is a community-based activity for health services in Indonesia. According to the Indonesian Basic Health Survey, the prevalence of children under five in Indonesia who suffered from being underweight was 19.6 %. The wasting was 12.1 % and the stunting was 37.2 % in 2013, and these values have not changed greatly from 2007; much greater than the WHO targets of, less than 10 % underweight, 5 % wasting, and 20 % stunting. In Aceh were 26.6, 16.8, and 43.3 %, respectively. Also, the participation percentages of mothers to Posyandu was about 45 %, far below the national target of 100 %. In Aceh Province, the percentage was even lower (34 % in 2013). This study aimed to investigate the factors influencing participation of mothers in Posyandu. METHODS: This research used a cross sectional design with sample of mothers who had children under five. They were chosen by multistage random sampling. Sample size was determined by the WHO formula. Face-to-face interviews were carried out using a questionnaire. The questionnaire consisted of items about socio-demographic characteristics, satisfaction with Posyandu services, attitude towards Posyandu benefits, and intention to attend Posyandu. The collected data were analyzed by using EZR (version 1.21). Fisher's exact test was performed to examine the associations between the socio-demographic factors, attitude, satisfaction, and intention covariates with participation. Logistic regression was used to describe the strength of the relationship between the predictor variables and participation. RESULTS: There were no significant differences in age, marital status, education level, occupation, family size, and distance to Posyandu between low participation group except for the monthly household income. Among the socio demographic factors, only monthly household income had a significant association with the frequency of mothers' participation. Satisfaction, attitude, and intention were associated with participation. The logistic regression showed that monitoring the nutritional status of children under five was the main reason that mothers participated in Posyandu. Mothers who were satisfied with the Posyandu services were more likely to attend than those who were dissatisfied. Respondents with intention to participate in Posyandu every month were more likely to attend than those who did not intend to attend every month. Households with low income were more likely to participate in Posyandu than households with high income. CONCLUSION: Household income, mothers' satisfaction with Posyandu services, attitude towards Posyandu benefits and intention to attend Posyandu affect the participation frequency of the mother. In addition, monitoring the nutritional status of children under five was the main reason respondents attend Posyandu. Improving the quality of Posyandu services and providing qualified resources are needed to promote mothers' participation. PMID- 26801624 TI - Clinicopathological analysis in patients with neuroendocrine tumors that metastasized to the brain. AB - BACKGROUND: A neuroendocrine tumor (NET) can develop anywhere in the body, but is mainly found in the pancreas, gastrointestinal tract, and lungs. This report is a retrospective study of the clinicopathological features of NET patients with brain metastasis whose tissue diagnosis was made at our hospital. METHODS: Patients with brain metastasis evidenced by clinical records and images were accumulated among 302 patients in whom tissue diagnosis of NETs was made at our hospital between 2008 and 2013. In the patients, the primary lesion, pathological classification, pattern of metastasis, details of treatment, and outcomes were analyzed. RESULTS: Brain metastasis was observed in 31 patients (10.3%). The primary lesion was in the lungs in 26 patients (83.9%), and the mammary glands, esophagus, and uterus in 1 patient each. Primary lesions were unknown in 2 patients, including 1 patient in whom NETs were detected in the lymph nodes alone. Pathological classification of the primary lesion was NET Grade 2 (Ki-67: 3 to 20%) in 3 patients and neuroendocrine carcinoma (NEC, Ki-67: >= 21%) in 26 patients. The median period from onset of the primary lesion up to diagnosis of brain metastasis was 12.8 months, and the brain lesion preceded brain metastasis in 6 patients. Ten patients had a single metastasis whereas 21 patients had multiple metastases, but no characteristics were observed in their images. Brain metastasis was extirpated in 10 patients. Stereotactic radiotherapy alone was administered in 6 patients, and brain metastasis was favorably controlled in most of the patients with coadministration of cranial irradiation as appropriate. The median survival period from diagnosis of brain metastasis was 8.1 months, and the major cause of death was aggravation of the primary lesion or metastatic lesions in other organs. CONCLUSION: Most of NET patients with brain metastasis showed the primary lesion of NEC in the lungs, and they had multiple metastases to the liver, lymph nodes, bones, and so forth at the time of diagnosis of brain metastasis. The guidelines for accurate diagnosis and treatment of NETs should be immediately established based on further analyses of NET patients with brain metastasis. PMID- 26801625 TI - Erratum to: Linear growth faltering in infants is associated with Acidaminococcus sp. and community-level changes in the gut microbiota. PMID- 26801623 TI - Comparative genome-wide transcriptome analysis of Vitis vinifera responses to adapted and non-adapted strains of two-spotted spider mite, Tetranyhus urticae. AB - BACKGROUND: The two-spotted spider mite, Tetranychus urticae, is an extreme generalist plant pest. Even though mites can feed on many plant species, local mite populations form host races that do not perform equally well on all potential hosts. An acquisition of the ability to evade plant defenses is fundamental for mite's ability to use a particular plant as a host. Thus, understanding the interactions between the plant and mites with different host adaptation status allows the identification of functional plant defenses and ways mites can evolve to avoid them. RESULTS: The grapevine genome-wide transcriptional responses to spider mite strains that are non-adapted and adapted to grapevine as a host were examined. Comparative transcriptome analysis of grapevine responses to these mite strains identified the existence of weak responses induced by the feeding of the non-adapted strain. In contrast, strong but ineffective induced defenses were triggered upon feeding of the adapted strain. A comparative meta-analysis of Arabidopsis, tomato and grapevine responses to mite feeding identified a core of 36 highly conserved genes involved in the perception, regulation and metabolism that were commonly induced in all three species by mite herbivory. CONCLUSIONS: This study describes the genome wide grapevine transcriptional responses to herbivory of mite strains that differ in their ability to use grapevine as a host. It raises hypotheses whose testing will lead to our understanding of grapevine defenses and mite adaptations to them. PMID- 26801626 TI - Early-stage atherosclerosis in poloxamer 407-induced hyperlipidemic mice: pathological features and changes in the lipid composition of serum lipoprotein fractions and subfractions. AB - BACKGROUND: The aims of this study were to evaluate the effect of poloxamer 407 administration on atherogenic serum lipoprotein fractions and subfractions associated with cholesterol, triglycerides and phospholipids, as well as the onset of early atherosclerosis, in mice. METHODS: Mice were administered either sterile saline or poloxamer 407 (to induce a dose-controlled hyperlipidemia) for 1 month and then sacrificed at 1, 4 and 10 days after the last dose of poloxamer 407. Systolic and diastolic blood pressure, the activity of a cysteine protease (cathepsin B) in cardiac and liver tissue, and histological/morphological examination of heart and liver specimens was performed for each group of mice at each time point. Lastly, small angle X-ray scattering was utilized to analyze the lipoprotein fractions and subfractions associated with cholesterol, triglycerides and phospholipids for both groups of mice at each time point. Statistical analysis was performed using one-way, analysis-of-variance with post hoc analysis to determine significantly different mean values, while correlation analysis employed the Spearman test. RESULTS: Poloxamer 407-treated mice revealed significant hyperlipidemia, moderately elevated blood pressure, general lipidosis in liver cells, increased cysteine protease activity in heart tissue, and contractile-type changes in cardiomyocytes. Similar to humans, the onset of atherosclerosis in poloxamer 407-treated mice was characterized by a steady increase in serum low-density, intermediate-density and very-low-density lipoprotein fractions, as well as very-low-density lipoprotein subfractions. CONCLUSIONS: We would propose that the sustained elevation of serum atherogenic lipoprotein fractions and subfractions induced by the administration of poloxamer 407 to mice resulted in the morphological changes we observed in both heart and liver cells, which are suggested to precede atherosclerosis, since this is a well established mouse model of atherosclerosis. Since most of the cellular, biochemical and physiological changes documented in the present study using poloxamer 407-treated mice are related to the symptoms of early atherosclerosis in humans, it is suggested that the poloxamer 407-induced mouse model of hyperlipidemia and atherosclerosis might prove beneficial as an experimental animal model with which to evaluate the pathological features observed in early stage atherosclerosis. PMID- 26801628 TI - Nasal tissue-derived hamartoma in the maxillary gingiva of a calf. AB - BACKGROUND: All of oral hamartomas has been previously found in mandibular gingiva in younger calves, and were histologically diagnosed as a vascular hamartoma. This is the first case report describing a calf with a mass in the maxillary gingiva that was histologically diagnosed as a nasal tissue-derived hamartoma. CASE PRESENTATION: A 13-day-old male Holstein calf presented with a horn-like mass in the left rostral maxillary gingiva. Surgical removal revealed that the mass had a dual structure composed of cartilaginous and soft tissues and extended deeply toward the nasal cavity. Excised tissues mainly consisted of two types of mature cells without mitotic figures and atypia: 1) the cartilage-like structures consisted of an island and a meandering massive focus of mature cartilaginous tissues, and 2) tubular structures consisting of stratified ciliated mucosal columnar cells with gland-like structures and aggregated goblet cells. The mass was diagnosed as a nasal tissue-derived hamartoma because these two types of structures were histologically identical to nasal structures. The present case had no recurrence at 1 year after surgery. CONCLUSIONS: To our knowledge, this is the first description of the calf with nasal tissue-derived hamartoma in the maxillary gingiva. PMID- 26801627 TI - Protein Phosphatase-1 regulates Rift Valley fever virus replication. AB - Rift Valley fever virus (RVFV), genus Phlebovirus family Bunyaviridae, is an arthropod-borne virus endemic throughout sub-Saharan Africa. Recent outbreaks have resulted in cyclic epidemics with an increasing geographic footprint, devastating both livestock and human populations. Despite being recognized as an emerging threat, relatively little is known about the virulence mechanisms and host interactions of RVFV. To date there are no FDA approved therapeutics or vaccines for RVF and there is an urgent need for their development. The Ser/Thr protein phosphatase 1 (PP1) has previously been shown to play a significant role in the replication of several viruses. Here we demonstrate for the first time that PP1 plays a prominent role in RVFV replication early on during the viral life cycle. Both siRNA knockdown of PP1alpha and a novel PP1-targeting small molecule compound 1E7-03, resulted in decreased viral titers across several cell lines. Deregulation of PP1 was found to inhibit viral RNA production, potentially through the disruption of viral RNA transcript/protein interactions, and indicates a potential link between PP1alpha and the viral L polymerase and nucleoprotein. These results indicate that PP1 activity is important for RVFV replication early on during the viral life cycle and may prove an attractive therapeutic target. PMID- 26801630 TI - User perspectives on an electronic decision-support tool performing comprehensive medication reviews - a focus group study with physicians and nurses. AB - BACKGROUND: Although a number of studies have evaluated the effectiveness of computerized decision-support systems (CDSS), there is lack of data on user perspectives, barriers, and facilitators to the implementation of CDSSs in real life surroundings. The aim of this study was to assess individually perceived barriers, facilitators and ideas influencing the CDSS implementation and usability. METHODS: In this qualitative study, five focus groups were carried out with physicians and nurses separately at the Tampere City Health Center, Finland. The participants were end-users of the EBMeDS computerized decision support system. An explorative data content analysis was applied. RESULTS: The most important barrier to benefitting from CDSS was the lack of structured and coded diagnosis documentation and outdated medication information in the electronic health records. This led to false alerts and distrust towards the system. Among the major facilitators found were e.g. the beneficial reminders that helped practitioners take into account matters otherwise ignored; automatic glomerular filtration rate (GFR) calculations; medication safety checks; and the summaries in the single medication review at a glance. CONCLUSIONS: Physicians' and nurses' are keen to use the CDSS and it may enhance their inter-professional collaboration. Documenting patient information in a structured, uniform and easy manner is the essential starting point for electronic decision support. When implementing CDSS, managers need to focus on common practices in documenting structured data in their organizations in order to prevent undermining trust in the system. PMID- 26801629 TI - Epidemiological and entomological studies of a malaria outbreak among French armed forces deployed at illegal gold mining sites reveal new aspects of the disease's transmission in French Guiana. AB - BACKGROUND: In December 2010, a Plasmodium vivax malaria outbreak occurred among French forces involved in a mission to control illegal gold mining in French Guiana. The findings of epidemiological and entomological investigations conducted after this outbreak are presented here. METHODS: Data related to malaria cases reported to the French armed forces epidemiological surveillance system were collected during the epidemic period from December 2010 to April 2011. A retrospective cohort study was conducted to identify presumed contamination sites. Anopheles mosquitoes were sampled at the identified sites using Mosquito Magnet and CDC light traps. Specimens were identified morphologically and confirmed using molecular methods (sequencing of ITS2 gene and/or barcoding). Anopheles infections with Plasmodium falciparum and P. vivax were tested by both enzyme-linked immunosorbent assay and real-time PCR. RESULTS: Seventy-two P. vivax malaria cases were reported (three were mixed P. falciparum/P. vivax infections), leading to a global attack rate of 26.5% (72/272). Lack of compliance with vector control measures and doxycycline chemoprophylaxis was reported by patients. Two illegal gold mining sites located in remote areas in the primary forest were identified as places of contamination. In all, 595 Anopheles females were caught and 528 specimens were formally identified: 305 Anopheles darlingi, 145 Anopheles nuneztovari s.l., 63 Anopheles marajoara and 15 Anopheles triannulatus s.l. Three An. darlingi were infected by P. falciparum (infection rate: 1.1%) and four An. marajoara by P. vivax (infection rate: 6.4%). DISCUSSION: The main drivers of the outbreak were the lack of adherence by military personnel to malaria prevention measures and the high level of malaria transmission at illegal gold mining sites. Anopheles marajoara was clearly implicated in malaria transmission for the first time in French Guiana. The high infection rates observed confirm that illegal gold mining sites must be considered as high level malaria transmission areas in the territory. CONCLUSIONS: Illegal gold mining activities are challenging the control of malaria in French Guiana. Collaboration with neighbouring countries is necessary to take into account mobile populations such as gold miners. Malaria control strategies in the French armed forces must be adapted to P. vivax malaria and sylvatic Anopheles species. PMID- 26801634 TI - Implementing a Test of Underlying Normality for Censored Variables. AB - This article describes the implementation of a standard Pearson chi-square statistic to test the null hypothesis of bivariate normality for the latent variables in the Type 1 censored model and discussed the need for such test. The behavior of the statistic is assessed by means of a series of simulation studies and illustrated by means of an empirical example. The limitations of the test are also discussed. PMID- 26801635 TI - The Bootstrap, the Jackknife, and the Randomization Test: A Sampling Taxonomy. AB - A simple sampling taxonomy is defined that shows the differences between and relationships among the bootstrap, the jackknife, and the randomization test. Each method has as its goal the creation of an empirical sampling distribution that can be used to test statistical hypotheses, estimate standard errors, and/or create confidence intervals. Distinctions between the methods can be made based on the sampling approach (with replacement versus without replacement) and the sample size (replacing the whole original sample versus replacing a subset of the original sample). The taxonomy is useful for teaching the goals and purposes of resampling schemes. An extension of the taxonomy implies other possible resampling approaches that have not previously been considered. Univariate and multivariate examples are presented. PMID- 26801632 TI - Graphic analysis of flow-volume curves: a pilot study. AB - BACKGROUND: Conventional spirometric parameters have shown poor correlation with symptoms and health status of chronic obstructive pulmonary disease (COPD). While it is well-known that the pattern of the expiratory flow-volume curve (EFVC) represents ventilatory dysfunction, little attempts have been made to derive quantitative parameters by analyzing the curve. In this study, we aimed to derive useful parameters from EFVC via graphic analysis and tried to validate them in patients with COPD. METHODS: Using Graphical Analysis 3.4 Vernier Software, we derived from the EFVC such parameters as area of obstruction (Ao), area of triangle (AT), area of rectangle (AR) and ratio of volume at 75 and 25% peak expiratory flow (PEF) (0.25/0.75 V). For validation, we reviewed clinical and spirometric data of 61 COPD patients from Seoul National University Airway Registry (SNUAR) and Korean obstructive Lung Disease (KOLD) cohorts. RESULTS: Of all parameters, only RV/TLC significantly correlated with scores from St. George's Respiratory Questionnaire (SGRQ) (r = 0.447, p = 0.037). Six-minute walking distance (6MWD) highly correlated with Ao/AR (r = -0.618, p = 0.005) and Ao/PEF (r = -0.581, p = 0.009) whereas neither FEV1 nor FEV1/FVC had significant correlation with 6MWD. CONCLUSIONS: Ao/AR and Ao/PEF are promising parameters which correlate well with the exercising capacity of COPD patients. PMID- 26801636 TI - Testing Multivariate Effect Sizes in Multiple-Endpoint Studies. AB - A common problem in meta-analysis is to test the equality of p correlated effected sizes for k independent studies in which a treatment is compared to a control group. For this problem, two situations arise in practice: all studies use the same outcome variables or some variables are missing. In this article we investigate these problems using Hotelling's generalized To 2 statistic. An example is used to illustrate the procedure. PMID- 26801633 TI - Epigenetic Upregulation of Metallothionein 2A by Diallyl Trisulfide Enhances Chemosensitivity of Human Gastric Cancer Cells to Docetaxel Through Attenuating NF-kappaB Activation. AB - AIMS: Metallothionein 2A (MT2A) and nuclear factor-kappaB (NF-kappaB) are both involved in carcinogenesis and cancer chemosensitivity. We previously showed decreased expression of MT2A and IkappaB-alpha in human gastric cancer (GC) associated with poor prognosis of GC patients. The present study investigated the effect of diallyl trisulfide (DATS), a garlic-derived compound, and docetaxel (DOC) on regulation of MT2A in relation to NF-kappaB in GC cells. RESULTS: DATS attenuated NF-kappaB signaling in GC cells, resulting in G2/M cell cycle arrest and apoptosis, culminating in the inhibition of cell proliferation and tumorigenesis in nude mice. The anti-GC effect of DATS was attributable to its capacity to epigenetically upregulate MT2A, which in turn enhanced transcription of IkappaB-alpha to suppress NF-kappaB activation in GC cells. The combination of DATS with DOC exhibited a synergistic anti-GC activity accompanied by MT2A upregulation and NF-kappaB inactivation. Histopathologic analysis of GC specimens from patients showed a significant increase in MT2A expression following DOC treatment. GC patients with high MT2A expression in tumor specimens showed significantly improved response to chemotherapy and prolonged survival compared with those with low MT2A expression in tumors. INNOVATION AND CONCLUSION: We conclude that DATS exerts its anti-GC activity and enhances chemosensitivity of GC to DOC by epigenetic upregulation of MT2A to attenuate NF-kappaB signaling. Our findings delineate a mechanistic basis of MT2A/NF-kappaB signaling for DATS- and DOC-mediated anti-GC effects, suggesting that MT2A may be a chemosensitivity indicator in GC patients receiving DOC-based treatment and a promising target for more effective treatment of GC by combination of DATS and DOC. Antioxid. Redox Signal. 24, 839-854. PMID- 26801637 TI - An Extension of the Propensity Score Adjustment Method for the Analysis of Group Differences in MIMIC Models. AB - This article proposes an extension of the propensity score adjustment method to latent variable models. The propensity score was proposed by Rosenbaum and Rubin (1983) as a means of balancing treatment and control groups with respect to observed covariates in non-randomized studies. The propensity score is defined as the conditional probability of assignment to a treatment group given a set of observed covariates. In a typical application of this approach, each observation is associated with a propensity to be assigned to the treatment group. The distribution of propensity scores is then divided into strata and analyses of treatment group differences are conducted within strata. Comparisons of treatment group differences within and across strata provide evidence for whether or not the bias due to non-random selection into treatment groups has been accounted for by the propensity score adjustment. This article extends the application of the propensity score approach to the analysis of group differences on latent variables. In particular, multi-sample MIMIC modeling is utilized to test hypotheses about treatment group differences on latent variables across strata. The role of factorial invariance as it relates to the approach advocated in this article is also discussed. An application to the problem of academic tracking differences in self-concept and locus-of-control, using data from the National Educational Longitudinal Study of 1988 (National Center for Education Statistics, 1988), illustrates the procedure. PMID- 26801638 TI - A Comparison of Methods for Constructing Confidence Intervals for the Squared Multiple Correlation Coefficient. AB - Four methods for constructing 100(1 - a)% confidence intervals for the population squared multiple correlation coefficient (r2) were compared. In one method the confidence interval was constructed by using the distribution of R2. Provided r2 > 0 the coverage probability for this method is exactly 1 - a when the data are multivariate normal. The other three methods are based on results in Olkin and Finn (1995) and are approximate. Results show that each of the approximate methods works very poorly for some combinations of r2. The method based on the distribution of R2 is recommended. PMID- 26801640 TI - Additive genetic variance in polyandry enables its evolution, but polyandry is unlikely to evolve through sexy or good sperm processes. AB - Polyandry is widespread despite its costs. The sexually selected sperm hypotheses ('sexy' and 'good' sperm) posit that sperm competition plays a role in the evolution of polyandry. Two poorly studied assumptions of these hypotheses are the presence of additive genetic variance in polyandry and sperm competitiveness. Using a quantitative genetic breeding design in a natural population of Drosophila melanogaster, we first established the potential for polyandry to respond to selection. We then investigated whether polyandry can evolve through sexually selected sperm processes. We measured lifetime polyandry and offensive sperm competitiveness (P2 ) while controlling for sampling variance due to male * male * female interactions. We also measured additive genetic variance in egg-to adult viability and controlled for its effect on P2 estimates. Female lifetime polyandry showed significant and substantial additive genetic variance and evolvability. In contrast, we found little genetic variance or evolvability in P2 or egg-to-adult viability. Additive genetic variance in polyandry highlights its potential to respond to selection. However, the low levels of genetic variance in sperm competitiveness suggest that the evolution of polyandry may not be driven by sexy sperm or good sperm processes. PMID- 26801639 TI - Depressive-like behavior, its sensitization, social buffering, and altered cytokine responses in rhesus macaques moved from outdoor social groups to indoor housing. AB - Psychosocial stressors appear to promote the onset of depressive illness through activation and sensitization of inflammatory mechanisms. Here, adult male rhesus monkeys brought from large outdoor social groups to indoor housing for 8 days reliably exhibited a hunched, depressive-like posture. When rehoused indoors a second 8 days about 2 weeks later, monkeys housed alone, but not those with an affiliative partner, showed sensitization of the depressive-like hunched posture. Housing indoors also affected circulating pro-inflammatory cytokines: IL-1beta showed increased responsiveness to immune challenge, and IL-1beta and TNF-alpha showed reduced suppression by dexamethasone. Sensitivity of the anti-inflammatory cytokine IL-10 to immune challenge exhibited a relative increase from the first to the second round of indoor housing in animals housed in pairs, and a relative decrease in animals housed alone. Cytokine levels during indoor housing were positively correlated with duration of depressive-like behavior. Plasma cortisol levels increased but did not differentiate housing conditions or rounds. Results demonstrate a rapid induction and sensitization of depressive-like behavior to indoor individual housing, social buffering of sensitization, and associated inflammatory responses. This paradigm may provide a practical nonhuman primate model for examining inflammatory-mediated consequences of psychosocial stressors on depression and possible social buffering of these effects. PMID- 26801642 TI - Multiple nucleic acid cleavage modes in divergent type III CRISPR systems. AB - CRISPR-Cas is an RNA-guided adaptive immune system that protects bacteria and archaea from invading nucleic acids. Type III systems (Cmr, Csm) have been shown to cleave RNA targets in vitro and some are capable of transcription-dependent DNA targeting. The crenarchaeon Sulfolobus solfataricus has two divergent subtypes of the type III system (Sso-IIID and a Cmr7-containing variant of Sso IIIB). Here, we report that both the Sso-IIID and Sso-IIIB complexes cleave cognate RNA targets with a ruler mechanism and 6 or 12 nt spacing that relates to the organization of the Cas7 backbone. This backbone-mediated cleavage activity thus appears universal for the type III systems. The Sso-IIIB complex is also known to possess a distinct 'UA' cleavage mode. The predominant activity observed in vitro depends on the relative molar concentration of protein and target RNA. The Sso-IIID complex can cleave plasmid DNA targets in vitro, generating linear DNA products with an activity that is dependent on both the cyclase and HD nuclease domains of the Cas10 subunit, suggesting a role for both nuclease active sites in the degradation of double-stranded DNA targets. PMID- 26801641 TI - Enrichment of Cdk1-cyclins at DNA double-strand breaks stimulates Fun30 phosphorylation and DNA end resection. AB - DNA double-strand breaks (DSBs) are one of the most cytotoxic types of DNA lesion challenging genome integrity. The activity of cyclin-dependent kinase Cdk1 is essential for DSB repair by homologous recombination and for DNA damage signaling. Here we identify the Fun30 chromatin remodeler as a new target of Cdk1. Fun30 is phosphorylated by Cdk1 on Serine 28 to stimulate its functions in DNA damage response including resection of DSB ends. Importantly, Cdk1-dependent phosphorylation of Fun30-S28 increases upon DNA damage and requires the recruitment of Fun30 to DSBs, suggesting that phosphorylation increases in situ at the DNA damage. Consistently, we find that Cdk1 and multiple cyclins become highly enriched at DSBs and that the recruitment of Cdk1 and cyclins Clb2 and Clb5 ensures optimal Fun30 phosphorylation and checkpoint activation. We propose that the enrichment of Cdk1-cyclin complexes at DSBs serves as a mechanism for enhanced targeting and modulating of the activity of DNA damage response proteins. PMID- 26801643 TI - Sequence-independent characterization of viruses based on the pattern of viral small RNAs produced by the host. PMID- 26801644 TI - Low postoperative nonstimulated thyroglobulin as a criterion for the indication of low radioiodine activity in patients with papillary thyroid cancer of intermediate risk 'with higher risk features'. AB - OBJECTIVE: This study evaluated low-activity (131) I therapy in patients with papillary thyroid carcinoma (PTC) of intermediate risk 'with higher risk features' who had low nonstimulated thyroglobulin (Tg) after thyroidectomy. DESIGN AND PATIENTS: This was a prospective study including 102 patients with tumours >1 cm and aggressive histology; and/or >3 positive lymph node (LN) or LN >1.5 cm or exhibiting macroscopic extracapsular extension, and clinically apparent (cN1); and/or a combination of a tumour >4 cm, microscopic extrathyroidal extension and LN metastases (cN1). After thyroidectomy, all patients had nonstimulated Tg < 0.3 ng/ml and negative antithyroglobulin antibodies (TgAb) and neck ultrasonography (US). The patients were treated with a low activity of (131) I (1110 or 1850 MBq). RESULTS: Post-therapy whole-body scanning (RxWBS) showed ectopic uptake in four patients. When evaluated 12 months after (131) I therapy, nonstimulated Tg <= 0.2 ng/ml with negative TgAb and US, defined as excellent response to initial therapy, was achieved in 101 patients (99%). Only one patient with positive initial RxWBS had structural disease. During follow-up, four patients (4%) relapsed, including LN metastases in two, pulmonary metastases in one, and elevated Tg in one. The other 98 patients remained with nonstimulated Tg <= 0.2 ng/ml and negative TgAb and US. There was no case of death due to the tumour. CONCLUSIONS: We conclude that in intermediate risk patients 'with higher risk features', low nonstimulated Tg measured with a second-generation assay can be used as criterion for the administration of low (131) I activities (1850 MBq or less). PMID- 26801645 TI - Differential Expression of Genes Involved in Host Recognition, Attachment, and Degradation in the Mycoparasite Tolypocladium ophioglossoides. AB - The ability of a fungus to infect novel hosts is dependent on changes in gene content, expression, or regulation. Examining gene expression under simulated host conditions can explore which genes may contribute to host jumping. Insect pathogenesis is the inferred ancestral character state for species of Tolypocladium, however several species are parasites of truffles, including Tolypocladium ophioglossoides. To identify potentially crucial genes in this interkingdom host switch, T. ophioglossoides was grown on four media conditions: media containing the inner and outer portions of its natural host (truffles of Elaphomyces), cuticles from an ancestral host (beetle), and a rich medium (Yeast Malt). Through high-throughput RNASeq of mRNA from these conditions, many differentially expressed genes were identified in the experiment. These included PTH11-related G-protein-coupled receptors (GPCRs) hypothesized to be involved in host recognition, and also found to be upregulated in insect pathogens. A divergent chitinase with a signal peptide was also found to be highly upregulated on media containing truffle tissue, suggesting an exogenous degradative activity in the presence of the truffle host. The adhesin gene, Mad1, was highly expressed on truffle media as well. A BiNGO analysis of overrepresented GO terms from genes expressed during each growth condition found that genes involved in redox reactions and transmembrane transport were the most overrepresented during T. ophioglossoides growth on truffle media, suggesting their importance in growth on fungal tissue as compared to other hosts and environments. Genes involved in secondary metabolism were most highly expressed during growth on insect tissue, suggesting that their products may not be necessary during parasitism of Elaphomyces. This study provides clues into understanding genetic mechanisms underlying the transition from insect to truffle parasitism. PMID- 26801646 TI - Identification of Polymorphisms Associated with Drought Adaptation QTL in Brassica napus by Resequencing. AB - Brassica napus is a globally important oilseed for which little is known about the genetics of drought adaptation. We previously mapped twelve quantitative trait loci (QTL) underlying drought-related traits in a biparental mapping population created from a cross between winter and spring B. napus cultivars. Here we resequence the genomes of the mapping population parents to identify genetic diversity across the genome and within QTL regions. We sequenced each parental cultivar on the Illumina HiSeq platform to a minimum depth of 23 * and performed a reference based assembly in order to describe the molecular variation differentiating them at the scale of the genome, QTL and gene. Genome-wide patterns of variation were characterized by an overall higher single nucleotide polymorphism (SNP) density in the A genome and a higher ratio of nonsynonymous to synonymous substitutions in the C genome. Nonsynonymous substitutions were used to categorize gene ontology terms differentiating the parent genomes along with a list of putative functional variants contained within each QTL. Marker assays were developed for several of the discovered polymorphisms within a pleiotropic QTL on chromosome A10. QTL analysis with the new, denser map showed the most associated marker to be that developed from an insertion/deletion polymorphism located in the candidate gene Bna.FLC.A10, and it was the only candidate within the QTL interval with observed polymorphism. Together, these results provide a glimpse of genome-wide variation differentiating annual and biennial B. napus ecotypes as well as a better understanding of the genetic basis of root and drought phenotypes. PMID- 26801647 TI - Implementation of the Realized Genomic Relationship Matrix to Open-Pollinated White Spruce Family Testing for Disentangling Additive from Nonadditive Genetic Effects. AB - The open-pollinated (OP) family testing combines the simplest known progeny evaluation and quantitative genetics analyses as candidates' offspring are assumed to represent independent half-sib families. The accuracy of genetic parameter estimates is often questioned as the assumption of "half-sibling" in OP families may often be violated. We compared the pedigree- vs. marker-based genetic models by analysing 22-yr height and 30-yr wood density for 214 white spruce [Picea glauca (Moench) Voss] OP families represented by 1694 individuals growing on one site in Quebec, Canada. Assuming half-sibling, the pedigree-based model was limited to estimating the additive genetic variances which, in turn, were grossly overestimated as they were confounded by very minor dominance and major additive-by-additive epistatic genetic variances. In contrast, the implemented genomic pairwise realized relationship models allowed the disentanglement of additive from all nonadditive factors through genetic variance decomposition. The marker-based models produced more realistic narrow-sense heritability estimates and, for the first time, allowed estimating the dominance and epistatic genetic variances from OP testing. In addition, the genomic models showed better prediction accuracies compared to pedigree models and were able to predict individual breeding values for new individuals from untested families, which was not possible using the pedigree-based model. Clearly, the use of marker based relationship approach is effective in estimating the quantitative genetic parameters of complex traits even under simple and shallow pedigree structure. PMID- 26801648 TI - A Simultaneous Genetic Screen for Zygotic and Sterile Mutants in a Hermaphroditic Vertebrate (Kryptolebias marmoratus). AB - The mangrove killifish, Kryptolebias marmoratus, is unique among vertebrates due to its self-fertilizing mode of reproduction involving an ovotestis. As a result, it constitutes a simplistic and desirable vertebrate model for developmental genetics as it is easily maintained, reaches sexual maturity in about 100 days, and provides a manageable number of relatively clear embryos. After the establishment and characterization of an initial mutagenesis pilot screen using N ethyl-N-nitrosourea, a three-generation genetic screen was performed to confirm zygotic mutant allele heritability and simultaneously score for homozygous recessive mutant sterile F2 fish. From a total of 307 F2 fish screened, 10 were found to be 1 degrees males, 16 were sterile, 92 wild-type, and the remaining 189, carriers of zygotic recessive alleles. These carriers produced 25% progeny exhibiting several zygotic phenotypes similar to those previously described in zebrafish and in the aforementioned pilot screen, as expected. Interestingly, new phenotypes such as golden yolk, no trunk, and short tail were observed. The siblings of sterile F2 mutants were used to produce an F3 generation in order to confirm familial sterility. Out of the 284 F3 fish belonging to 10 previously identified sterile families, 12 were found to be 1 degrees males, 69 were wild type, 83 sterile, and 120 were classified as */+ (either wild-type or carriers) with undefined genotypes. This screen provides proof of principle that K. marmoratus is a powerful vertebrate model for developmental genetics and can be used to identify mutations affecting fertility. PMID- 26801650 TI - Suprachiasmatic Nucleus and Subparaventricular Zone Lesions Disrupt Circadian Rhythmicity but Not Light-Induced Masking Behavior in Nile Grass Rats. AB - The ventral subparaventricular zone (vSPVZ) receives direct retinal input and influences the daily patterning of activity in rodents, making it a likely candidate for the mediation of acute behavioral responses to light (i.e., masking). We performed chemical lesions aimed at the vSPVZ of diurnal grass rats (Arvicanthis niloticus) using N-methyl-D,L-aspartic acid (NMA), a glutamate agonist. Following NMA lesions, we placed grass rats in various lighting conditions (e.g., 12:12 light-dark, constant dark, constant light); presented a series of light pulses at circadian times (CT) 6, 14, 18, and 22; and placed them in a 7-h ultradian cycle to assess behavioral masking. Extensive bilateral lesions of the vSPVZ disrupted the expression of circadian rhythms of activity and abolished the circadian modulation of masking responses to light, without affecting light-induced masking behavior per se. We also found that in diurnal grass rats, NMA was capable of destroying not only neurons of the vSPVZ but also those of the suprachiasmatic nucleus (SCN), even though excitotoxins have been ineffective at destroying cells within the SCN of nocturnal rodents. The vulnerability of the grass rat's SCN to NMA toxicity raises the possibility of a difference in density of receptors for glutamate between nocturnal and diurnal species. In cases in which damage extended to the SCN, masking responses to light were present and similar to those displayed by animals with damage restricted to the vSPVZ. Thus, extensive bilateral lesions of the SCN and vSPVZ disrupted the expression of circadian rhythms without affecting acute responses to light in a diurnal species. Our present and previous results suggest that retinorecipient brain areas other than the SCN or vSPVZ, such as the intergeniculate leaflet or olivary pretectal nucleus, may be responsible for the mediation of masking responses to light in the diurnal grass rat. PMID- 26801649 TI - Genome-Wide Investigation of MicroRNAs and Their Targets in Response to Freezing Stress in Medicago sativa L., Based on High-Throughput Sequencing. AB - Winter damage, especially in northern climates, is a major limitation of the utilization of perennial forages such as alfalfa. Therefore, improving freezing tolerance is imperative in alfalfa genetic breeding. However, freezing tolerance is a complex trait that is determined by many genes. To understand the complex regulation mechanisms of freezing tolerance in alfalfa, we performed small RNA sequencing analysis under cold (4 degrees ) and freezing (-8 degrees ) stress. The sequencing results revealed that 173 known, and 24 novel miRNAs were expressed, and that the expression of 35 miRNAs was affected by cold and/or freezing stress. Meanwhile, 105 target genes cleaved by these miRNAs were characterized by degradome sequencing. These targets were associated with biological regulation, cellular processes, metabolic processes, and response to stress. Interestingly, most of them were characterized as transcription factors (TFs), including auxin response factors, SBP, NAC, AP2/ERF, and GRF, which play important roles in plant abiotic responses. In addition, important miRNAs and mRNAs involved in nodulation were also identified, for example, the relationship between miR169 and the TF CCAAT (also named as NF-YA/HAP2), which suggested that nodulation has an important function in freezing tolerance in alfalfa. Our results provide valuable information to help determine the molecular mechanisms of freezing tolerance in alfalfa, which will aid the application of these miRNAs and their targets in the improvement of freezing tolerance in alfalfa and related plants. PMID- 26801651 TI - Computational Architecture of the Granular Layer of Cerebellum-Like Structures. AB - In the adaptive filter model of the cerebellum, the granular layer performs a recoding which expands incoming mossy fibre signals into a temporally diverse set of basis signals. The underlying neural mechanism is not well understood, although various mechanisms have been proposed, including delay lines, spectral timing and echo state networks. Here, we develop a computational simulation based on a network of leaky integrator neurons, and an adaptive filter performance measure, which allows candidate mechanisms to be compared. We demonstrate that increasing the circuit complexity improves adaptive filter performance, and relate this to evolutionary innovations in the cerebellum and cerebellum-like structures in sharks and electric fish. We show how recurrence enables an increase in basis signal duration, which suggest a possible explanation for the explosion in granule cell numbers in the mammalian cerebellum. PMID- 26801652 TI - Mercury Concentrations in Eggs of Red-Winged Blackbirds and Tree Swallows Breeding in Voyageurs National Park, Minnesota. AB - Most investigations of the environmental effects of mercury (Hg) have focused on aquatic food webs that include piscivorous fish or wildlife. However, recent investigations have shown that other species, including passerine songbirds, may also be at risk from exposure to methylmercury (MeHg). We quantified Hg concentrations in eggs of two species of songbirds, red-winged blackbirds (Agelaius phoeniceus) and tree swallows (Tachycineta bicolor), nesting in Voyageurs National Park, Minnesota, USA. Geometric mean concentrations of total Hg (THg) were lower in red-winged blackbird eggs [218 and 107 ng/g dry weight (dw) for 2012 and 2013, respectively] than in tree swallow eggs (228 and 300 ng/g dw for 2012 and 2013, respectively), presumably reflecting differences in the trophic positions of these two species. Concentrations of MeHg averaged 98.4 % of THg in red-winged blackbird eggs. Levels of THg observed in this study were well below critical toxicological benchmarks commonly applied to eggs of avian species, suggesting these breeding populations were not adversely affected by exposure to MeHg. In red-winged blackbirds, concentrations of THg in eggs collected in 2012 were twice those in eggs collected in 2013. Hg levels in eggs of both species increased with date of clutch initiation. In red-winged blackbirds, for example, temporal patterns showed that a 3-week delay in clutch initiation increased egg THg by 60 %. These observations indicate that in ovo exposure of wetland birds to MeHg can vary significantly within nesting season as well as between years. PMID- 26801653 TI - Clinical outcomes of trabeculectomy versus Ahmed glaucoma valve implantation in patients with penetrating keratoplasty. PMID- 26801654 TI - Nausea and Vomiting During Pregnancy is Highly Heritable. AB - Nausea and vomiting during pregnancy (NVP) affects about 70 % of all expectant mothers and commonly impacts their physical health and psychosocial functioning. The aim of this study was to estimate the heritability of the presence, duration and severity of NVP. The sample consisted of 1723 women (M age = 41.78, SD = 11.67) including twins in both complete and incomplete pairs and their sisters from two cohorts participating in the NVP Genetics Consortium. The sample comprised 159 monozygotic and 140 dizygotic complete twin pairs, and 69 twin sister pairs. We applied an extended twin design using OpenMx and Mx for secondary analysis. Individual differences in NVP were best explained by additive genetic and unique environmental effects. Heritability estimates were 73 % (95 % CIs = 57-84 %) for presence, 51 % (95 % CIs = 36-63 %) for duration and 53 % (95 % CIs = 38-65 %) for severity of NVP. The genetic correlation between duration and severity was almost perfect. Our results show that genes play an important role in different aspects of NVP and justify the importance of searching for genetic variants. PMID- 26801656 TI - Assessment of Postgraduate Year 2 Pharmacy Residency Programs Within the Veterans Affairs Healthcare System. AB - PURPOSE: Despite the increasing importance placed on advanced training for clinical pharmacists, literature describing postgraduate year 2 (PGY2) residency opportunities is limited. The objective of this study was to describe characteristics of PGY2 programs within the Veterans Affairs (VA) healthcare system. METHODS: An online survey addressing attributes of PGY2 residency programs was electronically distributed to VA residency program directors (RPDs). RESULTS: Responses from 27 (32.9%) VA PGY2 residency programs were included, representing 11 distinct PGY2 specialties. Growth and recruitment trends were similar across programs, with most programs projecting additional expansion. Staffing requirements were uncommon, but opportunities to precept and earn teaching certificates were prevalent. RPDs had been licensed pharmacists an average of 16.9 years, and most had at least 1 advanced certification. The majority of programs had a formal residency advisory committee and required preceptors to attend regular development meetings. CONCLUSION: Although multiple postgraduate specialties were represented, the requirements and opportunities available for PGY2 pharmacy residents were similar across VA facilities. By comparing residency programs in a nationally integrated health-care system, this study may promote growth of existing PGY2 programs, facilitate the establishment of new programs, and provide a framework for prospective residents to evaluate programs of interest. PMID- 26801657 TI - Docetaxel/Cyclophosphamide-Induced Phototherapy Recall. AB - Phototherapy recall can occur unexpectedly as a result of treatment with commonly used medications and chemotherapy. These reactions are rare. The recall reaction is an inflammatory response that is triggered by many medications. Cyclophosphamide and docetaxel are widely used chemotherapeutic agents that are useful in the management of many different malignancies. The pathophysiology of phototherapy recall is not clearly understood. This case highlights the need for practitioners to be aware of this potential reaction, even though UV exposure may have occurred in the distant past. We present, to the best of our knowledge, the first phototherapy recall dermatitis that occurred years after UV exposure induced by cyclophosphamide and docetaxel. The frequency of administration of this drug and the profound implications of this adverse effect make this case an important contribution to the medical literature. PMID- 26801655 TI - A Systematic Review and Network Meta-Analysis to Assess the Relative Efficacy of Antipsychotics for the Treatment of Positive and Negative Symptoms in Early-Onset Schizophrenia. AB - INTRODUCTION: Early-onset schizophrenia (EOS) is a serious debilitating disorder with considerable morbidity and a reduced life expectancy; therefore, early diagnosis and effective treatments are particularly important. Negative symptoms are more prominent in adolescents and children (compared with adults), and are key predictors of worse functional and clinical outcomes in EOS. Therefore, this study aimed to explore the relative efficacy of antipsychotics used in the treatment of EOS, with a focus on studies reporting effectiveness using the Positive and Negative Syndrome scale (PANSS), a scale that includes an overall symptom measure, in addition to separate subscales for positive and, importantly, negative symptoms. METHODS: A systematic literature review was conducted using the MEDLINE and Cochrane Central Register of Controlled Trials databases to identify trials conducted in children and adolescents with schizophrenia, and symptom control was reported using the PANSS. A Bayesian random-effects network meta-analysis was performed, synthesising data for a number of outcomes, including mean change from baseline in PANSS scores, treatment discontinuation and weight gain. RESULTS: Eleven studies were included in the evidence synthesis, comprising 1714 patients across eight active interventions (aripiprazole, haloperidol, molindone, olanzapine, paliperidone, quetiapine, risperidone and ziprasidone) and placebo. All treatments showed a greater reduction in total PANSS scores vs placebo; however, only three interventions (molindone, olanzapine and risperidone) were associated with a statistically significant reduction in total PANSS scores at 6 weeks vs placebo. Haloperidol had the greatest reduction vs placebo; however, this result was not statistically significant [mean difference, -15.6, 95% credible interval (-35.4, 4.1)]. Haloperidol, olanzapine and risperidone showed a statistically significant reduction in positive PANSS scores vs placebo; however, whilst all interventions showed a trend of reduction in negative PANSS scores vs placebo, no comparisons were statistically significant. CONCLUSIONS: Many of the treatments are efficacious in controlling symptoms, and all showed a trend of superiority vs placebo for total, positive and negative PANSS scores, although only olanzapine and risperidone yielded statistically significant results vs placebo for both total and positive PANSS scores. Varying results for discontinuation and weight gain demonstrate a need to balance efficacy with side-effect profiles. PMID- 26801658 TI - Levodopa Withdrawal Presenting as Fever in a Critically Ill Patient Receiving Concomitant Enteral Nutrition. AB - Nutritional protein may decrease levodopa absorption and has resulted in withdrawal and neuroleptic malignant-like syndromes in critically ill patients. A 72-year-old male was admitted with shortness of breath. His medical history included Parkinson's disease for over 30 years for which he took carbidopa/levodopa 5 times daily. The patient's home medications were continued. On day 2, he was intubated and transferred to the intensive care unit (ICU). He was extubated the next day and reintubated on day 4. Enteral nutrition was initiated at 85 mL/h overnight. The patient's carbidopa/levodopa was administered to limit coadministration with nutrition. Throughout his ICU stay, the patient did not demonstrate changes in mental status. Despite resolution of his pneumonia, he developed fever after administration of one dose overlapping with nutrition, with defervescence throughout the rest of the day. On hospital day 10, that dose was empirically increased. After this dosing change, the patient failed to develop fever during the rest of his hospital stay. On day 16, the patient was discharged to a long-term care facility without any other complications. Our case highlights the interaction between levodopa and enteral nutrition and the potential of fever as the sole sign of withdrawal. PMID- 26801659 TI - Effectiveness of tranexamic acid in reducing blood loss during cytoreductive surgery for advanced ovarian cancer. AB - BACKGROUND: Ovarian cancer is the third most common gynaecological cancer worldwide, with an age-standardised incidence rate of 6.1 per 10,000 women. Standard therapy for advanced epithelial ovarian cancer (EOC) includes a combination of cytoreductive surgery and platinum-based chemotherapy. Cytoreductive surgery aims to remove as much of the visible tumour as possible. As extensive intraperitoneal metastases are typical of advanced EOC, cytoreductive surgery is usually an extensive procedure with the risk of excessive bleeding. Tranexamic acid given perioperatively is effective in reducing blood loss and allogeneic blood transfusion requirements in a variety of surgical settings. Therefore, tranexamic acid seems to be a promising agent for minimising blood loss and the need for blood transfusion among women with advanced EOC undergoing cytoreductive surgery. OBJECTIVES: To assess the effects of tranexamic acid for reducing blood loss associated with cytoreductive surgery in women with advanced EOC (stage III to IV). SEARCH METHODS: We searched the Cochrane Gynaecological, Neuro-oncology and Orphan Cancers Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 5, 2015), MEDLINE, EMBASE and conference proceedings to May 2015. We also checked registers of clinical trials, citation lists of included studies, key textbooks and previous systematic reviews for potentially relevant studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing tranexamic acid given during surgery versus placebo or no treatment, in adult women diagnosed with advanced EOC. DATA COLLECTION AND ANALYSIS: Two review authors (CK, AS) independently selected potentially relevant trials, extracted data, assessed risk of bias, compared results and resolved disagreements by discussion. MAIN RESULTS: We found only one study that met our inclusion criteria. This was a randomised double blind, placebo-controlled multicentre study conducted to evaluate the effectiveness of a single dose of intravenous tranexamic acid (15 mg/kg body weight) versus placebo, given immediately before surgery for reducing blood loss and the need for red blood cell transfusion. The mean total estimated blood loss was 668.34 mL and 916.93 mL for participants assigned to tranexamic acid and placebo groups, respectively. The mean difference (MD) of total estimated blood loss between the groups did not show a clinically important effect (MD - 248.59 mL; 95% confidence interval (CI) - 550.9 to 53.79; one study, 100 participants; moderate quality evidence). The mean number of transfused units of blood components was not different between the two groups (low quality evidence). There were no noted differences in the incidence of reoperation, readmission or thromboembolic events (very low quality evidence). We considered the methodology of the included study to be at low risk of selection, detection, and reporting biases. However, we were concerned about an imbalance of some baseline characteristics between the groups, and as there was no protocol for blood transfusion, the rate of blood transfusion may vary depending on the practice of each participating hospital. AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence to recommend the routine use of tranexamic acid for reducing blood loss in women undergoing cytoreductive surgery for advanced EOC, as only limited data are available from a single, low quality RCT at low overall risk of bias. PMID- 26801660 TI - miR-483-3p plays an oncogenic role in esophageal squamous cell carcinoma by targeting tumor suppressor EI24. AB - microRNAs (miRNAs), through negatively regulating their target genes, influence the development and progression of many cancers. Previously, we found miR-483 was overexpressed in esophageal squamous cell carcinoma (ESCC) tissues, and its overexpression was negatively correlated with the prognosis and positively correlated with multidrug resistance of ESCC, but whether it could affect the biological role of proliferation and migration in ESCC cell lines is unknown. In the present study, we found miR-483-3p was overexpressed in ESCC cell lines as compared with the normal esophageal squamous epithelial cell line. Functional experiments in vitro showed that miR-483-3p could promote the proliferation, migration, transformation of cell cycle from G1 phase to G2 phase of ESCC cells and could inhibit cells' sensitivity to chemotherapy drugs. Nude mouse tumorigenicity assay indicated that miR-483-3p could promote the growth of ESCC cells in vivo. Western blot assay showed that ectopic expression of miR-483-3p in ESCC cells could downregulate the protein level of etoposide induced 2.4 (EI24), which is a tumor suppressor and has not been reported in ESCC. Luciferase reporter assay demonstrated that EI24 was a direct target of miR-483-3p. Collectively, our study demonstrated that miR-483-3p could promote ESCC progression at least in part through directly targeting EI24, supplying a potential strategy for miRNA-based ESCC therapy. PMID- 26801661 TI - Toxic chemicals and thyroid function: hard facts and lateral thinking. AB - Increasing quantities of evidence-based data incriminate a large number of environmental pollutants for toxic effects on the thyroid. Among the many chemical contaminants, halogenated organochlorines and pesticides variably affect the hypothalamic-pituitary-thyroid axis and disrupt thyroid function. PCBs and their metabolites and PBDEs bind to thyroid transport proteins, such as transthyretin, displace thyroxine, and disrupt thyroid function. Meanwhile, at the molecular level, PCB congeners may activate phosphorylation of Akt, p-Akt, and forkhead box O3a (FoxO3a) protein resulting in inhibition of the natrium/iodide symporter. Given therefore the growing concern developing around these multiple toxic chemicals today invading numerous environments and their long-term deleterious effects not only on the thyroid but also on general health, we strongly advocate their strict regulation and, moreover, their gradual reduction. A good degree of "lateral thinking", we feel, will lead to a use of chemicals that will enhance life while concurrently carefully protecting the environment. PMID- 26801662 TI - Impact of parametric imaging on contrast-enhanced ultrasound of breast cancer. AB - PURPOSE: To prospectively evaluate the usefulness of contrast-enhanced ultrasound (CEUS) using parametric imaging for breast cancer in a multicenter study. METHODS: A total of 65 patients with breast cancer were included in this study. CEUS was performed, and still images on peak time (S), accumulated images (A) and parametric images (P) were generated from the raw data. Four blind reviewers ranked the best visible images as first place, and determined second and third place consecutively. We compared the average ranking of each image. The maximal diameter of the tumor determined on ultrasonography and MRI was compared with the corresponding pathological maximal diameter for 48 of the 65 patients. The correlation between the diameter determined by two experts and two beginners was analyzed. RESULTS: The average rank of visibility was as follows: P, 1.44; A, 2.04; and S, 2.52. The correlation between each image and the pathology was as follows: P, r = 0.664; A, r = 0.630; S, r = 0.717; and MRI, r = 0.936. There were no significant differences among the correlation between the experts and beginners in each image. CONCLUSIONS: The use of parametric imaging improves the visibility of CEUS. The maximal diameter of the tumor determined on CEUS correlates substantially with the pathology. PMID- 26801665 TI - Dramatic improvement of neglect after cranioplasty: a causal or casual relationship? PMID- 26801663 TI - Understanding arterial load. PMID- 26801666 TI - Comparison of morphological features in the femur between femoral neck fractures and femoral intertrochanteric fractures. AB - PURPOSE: The purpose of this study is to make proximal femur fracture types more predictable by considering morphological features of an acetabulum as well as of a proximal femur in the Japanese population. METHODS: A retrospective review of radiographs of the proximal femoral fractures was conducted in patients registered from 2010 to 2012, dividing into patients with femoral neck fractures; Group Neck (n = 101), and patients with femoral intertrochanteric fractures; Group IT (n = 99). Intergroup comparison was conducted: age, sex, height, weight, the ratios of femoral intertrochanteric length (IT Length), femoral neck length (Neck Length), femoral neck width (Neck Width), lateral offset length (Offset) to femoral head diameter, neck-shaft angle (N-S angle), and center-edge angle of the acetabulum (C-E angle), adjusting for age. Multiple logistic regression analysis was conducted among these parameters. RESULTS: The Group IT showed significantly older age than the Group Neck. Greater C-E angle in Group IT was observed in the patients in their 80s and 90s years of age. The Group Neck showed greater N-S angle only in the patients in their 80s years of age. In multiple logistic regression analysis, the impact of the age and the C-E angle on the fracture types was similar (odds ratio 1.08, 1.09, respectively, p < 0.01 both). CONCLUSIONS: Age, N-S angle, and C-E angle could be independent predictors for determining the proximal femur fracture types. PMID- 26801667 TI - Re-Emergence of a Novel H5N1 Avian Influenza Virus Variant Subclade 2.2.1.1 in Egypt During 2014. AB - Large-scale surveillance is crucial for understanding the evolution and the emergence of avian influenza viruses (AIVs) in endemic areas. Circulation of highly pathogenic avian influenza (HPAI) subtype H5N1 is continuously causing significant economic losses to the Egyptian poultry industry and is a threat to public health. In this report, a HPAI H5N1 strain (A/chicken/Egypt/Fadllah 7/2014) was detected from a vaccinated flock showing clinical signs of infection. Genetic characterization of the isolate indicated a high level of nucleotide identity (95-98%) with variant and classical groups of H5N1. Moreover, multiple nucleotide and amino acid alignments revealed several prominent and characteristic substitutions in the surface glycoprotein, which may have biological relevance to the pathobiology of the virus. Phylogenetic analysis demonstrated that the reported isolate closely relates to H5N1 AIVs subclade 2.2.1.1 in spite of no reports of this subclade since 2011 from AI reported cases in Egyptian avian species. In conclusion, our results highlight the re-emergence of a novel H5N1 AIV variant subclade 2.2.1.1 that could escape immunity induced by vaccines. This discovery illustrates the importance of continuous monitoring of poultry in this country for controlling AIV including identifying sources of vaccine seed viruses. PMID- 26801669 TI - Cloning and characterization of two distinct water-forming NADH oxidases from Lactobacillus pentosus for the regeneration of NAD. AB - Two uncharacterized nicotinamide adenine dinucleotide (NADH) oxidases (named as LpNox1, LpNox2) from Lactobacillus pentosus ATCC 8041 were cloned and overexpressed in Escherichia coli BL21 (DE3). The sequence analysis revealed that the two enzymes are water-forming Noxs with 64 % and 52 % identity to LbNox from Lactobacillus brevis DSM 20054. The optimal pH and temperature of the purified LpNox1 and LpNox2 were 7.0 and 8.0 and 35 and 40 degrees C, respectively, with K M of 99.0 MUM (LpNox1) and 27.6 MUM (LpNox2), and yielding catalytic efficiency k cat/K M of 1.0 and 0.2 MUM(-1) s(-1), respectively. Heat inactivation studies revealed that the two enzymes are relatively instable. The application of LpNox1 for the regeneration of NAD(+) was demonstrated by coupling with a glycerol dehydrogenase-catalyzed oxidation of glycerol to 1,3-dihydroxyacetone. The characteristics of the LpNox1 could prove to be of interest in industrial application such as NAD(+) regeneration in dehydrogenase-catalyzed oxidations. PMID- 26801668 TI - Phyto-synthesis of silver nanoparticles using Alternanthera tenella leaf extract: an effective inhibitor for the migration of human breast adenocarcinoma (MCF-7) cells. AB - In this study, phyto-synthesis of silver nanoparticles (AgNPs) was achieved using an aqueous leaf extract of Alternanthera tenella. The phytochemical screening results revealed that flavonoids are responsible for the AgNPs formation. The AgNPs were characterised using UV-visible spectrophotometer, field emission scanning microscopy/energy dispersive X-ray, transmission electron microscopy, fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction. The average size of the nanoparticles was found to be ~48 nm. The EDX results show that strong signals were observed for the silver atoms. The strong band appearing at 1601-1595 cm(-1) correspond to C-C stretching vibration from dienes in FT-IR spectrum indicating the formation of AgNPs. Human breast adenocarcinoma (MCF-7) cells treated with various concentrations of AgNPs showed a dose-dependent increase in cell inhibition. The IC50 value of the AgNPs was calculated to be 42.5 MUg mL(-1). The AgNPs showed a significant reduction in the migration of MCF 7 cells. PMID- 26801670 TI - Solvent-free enzymatic production of high quality cetyl esters. AB - A solvent-free biocatalytic process for the synthesis of high quality cetyl laurate, myristate, palmitate and stearate has been optimized. This enzymatic procedure follows the fundamental principles of the Green Chemistry and lead to sustainable products, which can be labeled as natural and conform to the principal requirements for its use in high value-added goods. The four esters selected are the main components of spermaceti, a mixture of waxes very appreciated in cosmetic and pharmacy because of its physical properties and emolliency, which was formerly extracted from the head of the sperm whales. In this paper, the influence of the amount of biocatalyst, the commercially available Novozym((r)) 435, and the temperature were studied in an open-air batch reactor before carrying out the synthesis in a high performance vacuum reactor with dry nitrogen input to shift the equilibrium towards product formation. Under optimal conditions, conversion was higher than 98.5 %. The characterization of the enzymatic cetyl esters puts in evidence that these are ultra-pure compounds, which have similar properties to the ones obtained through the conventional industrial processes with the extra benefit of being environmentally friendly. PMID- 26801671 TI - Low p21 level is necessary for the suppressive effects of micoRNA-31 on glioma cell migration and invasion. AB - MicroRNAs (miRNAs), a kind of endogenous non-coding RNAs, regulate gene expression through binding to the 3'-untranslational region (UTR) of target messenger RNAs (mRNAs) and act as endogenous agents of RNA interference, resulting in either mRNA degradation or translational repression. MiR-31 has been demonstrated to be associated with the development and progression of glioma. However, the underlying molecular mechanism remains largely unclear. In the present study, we demonstrated that miR-31 only inhibited the cell migration and invasion, as well as the expression of a known miR-31 target oncogene radixin, in U251 glioma cells that expressed low level of p21; however, miR-31 showed no above effects on glioma SHG44 cells that highly expressed p21. Moreover, upregulation of p21 in U251 cells reversed the suppressive effects of miR-31 on the cell migration and invasion, suggesting that low p21 level is necessary for the miR-31-mediated inhibitory effects on glioma. Furthermore, analysis for 35 glioma specimens showed that the expression of radixin was negatively correlated with the miR-31 level in glioma tissues with low p21 expression; however, no such correlation was found in glioma tissues with high p21 level, further supporting that the low p21 level is necessary for the suppressive effect of miR-31 on the expression of its target oncogenes. In summary, our study demonstrates that the suppressive effect of miR-31 on glioma cell migration and invasion is p21 dependent, and suggests that miR-31 may be used for the treatment of patients with p21-deficent glioma. PMID- 26801672 TI - NANOG regulates epithelial-mesenchymal transition and chemoresistance through activation of the STAT3 pathway in epithelial ovarian cancer. AB - NANOG is a key transcription factor that is overexpressed and plays an important role in various cancers. Its overexpression is associated with highly tumorigenic, drug-resistant, and poor prognosis. However, the underlying mechanism of action of NANOG in ovarian cancer remains unclear. Epithelial mesenchymal transition (EMT), which is a critical process in cancer invasion and metastasis, is also associated with drug resistance. We determined whether NANOG is associated with EMT and chemoresistance in epithelial ovarian cancer cells. NANOG expression was increased in epithelial ovarian cancer cells (HEY and SKOV3) compared with normal epithelial ovarian cells (Moody). Low expression of NANOG increased the expression of E-cadherin and decreased the expression of vimentin, beta-catenin, and Snail. Furthermore, the cell migration and invasion abilities were decreased. The multidrug resistance genes MDR-1 and GST-pi were also downregulated when NANOG was lowly expressed. The cells that were transfected with the si-NANOG plasmid were more sensitive to cisplatin compared with the cells that were transfected with empty vector. The data demonstrated that Stat3 was correlated with NANOG-mediated EMT and drug resistance. The silencing of Stat3 expression abrogated NANOG-mediated EMT changes and increased the sensitivity of the cells to chemotherapy. These results suggest that NANOG mediates EMT and drug resistance through activation of the Stat3 pathway in epithelial ovarian cancer. PMID- 26801673 TI - Biological characteristics of a novel giant cell tumor cell line derived from spine. AB - Giant cell tumor of bone(GCTB) is a special bone tumor for it consists of various cell types, and its biological characteristics is different from common benign or malignant neoplasm. In the present study, we report the biological features of a primary Asian GCTB cell line named GCTB28. We analyzed extensive properties of the GCTB28 cells including morphological observations, growth, cell cycle, karyotype, proliferation, proteins expression, surface biomarker verification, and tumorigenicity in nude mice. We found that the stromal cells of GCTB were endowed with self-renewal capacity and played dominant roles in GCTB development. Moreover, we confirmed that GCTB cells can be CD33(-)CD14(-) phenotype which was not in accord with previous study. This study provides an in vitro model system to investigate pathogenic mechanisms and molecular characteristics of GCTB and also provides a useful tool for researching the therapeutic targeting of GCTB. PMID- 26801674 TI - Tumour-suppressive role of PTPN13 in hepatocellular carcinoma and its clinical significance. AB - Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality and carries a dismal prognosis. The present study aimed to identify the tumour suppressive role and clinical implications of PTPN13 in HCC progression. We tested the effects of PTPN13 expression in proliferation, invasion, epithelial mesenchymal transition and associated pathways in HCC cell lines in vitro. Furthermore, its clinical relevance was evaluated in a tissue microarray analysis of samples from 282 HCC patients. Various HCC cell lines expressed relatively low PTPN13 protein levels in vitro. PTPN13 overexpression significantly inhibited the progression of HCC cells, possibly by inhibiting epithelial-mesenchymal transition through inactivation of the EGFR/ERK signalling pathway. Tissue microarray analysis revealed that high PTPN13 expression was correlated with a favourable prognosis in postoperative HCC patients. This study demonstrated the tumour suppressor, PTPN13, as an alternative therapeutic target for HCC. PMID- 26801675 TI - FKBP5 modulates the hippocampal connectivity deficits in depression: a study in twins. AB - The hippocampus is a key modulator of stress responses underlying depressive behavior. While FKBP5 has been found associated with a large number of stress related outcomes and hippocampal features, its potential role in modifying the hippocampal communication transfer mechanisms with other brain regions remains largely unexplored. The putative genetic or environmental roots of the association between depression and structural connectivity alterations of the hippocampus were evaluated combining diffusion weighted imaging with both a quantitative genetics approach and molecular information on the rs1360780 single nucleotide polymorphism, in a sample of 54 informative monozygotic twins (27 pairs). Three main results were derived from the present analyses. First, graph theoretical measures of hippocampal connectivity were altered in depression. Specifically, decreased connectivity strength and increased network centrality of the right hippocampus were found in depressed individuals. Second, these hippocampal alterations are potentially driven by familial factors (genes plus shared environment). Third, there is an additive interaction effect between FKBP5's rs1360780 variant and the graph-theoretical metrics of hippocampal connectivity to influence depression risk. Our data reveals alterations of the communication patterns between the hippocampus and the rest of the brain in depression, effects potentially driven by overall familial factors (genes plus shared twin environment) and modified by the FKBP5 gene. PMID- 26801676 TI - Cytomegalovirus in Australian blood donors: seroepidemiology and seronegative red blood cell component inventories. AB - BACKGROUND: Cytomegalovirus (CMV) can lead to severe disease in high-risk subpopulations. To prevent transfusion-transmitted CMV in these patient groups, the Australian Red Cross Blood Service maintains inventories of CMV-seronegative fresh blood components. STUDY DESIGN AND METHODS: Donor demographic data and CMV seroscreening results for all blood donations and blood components issued in Australia between financial years (FYs) 2008/09 to 2012/13 inclusive were obtained. Population estimates were also extracted for the calculation of age weighted seroprevalence estimates. Linear regression was used to model trends in red blood cell (RBC) component acquisition and demand. RESULTS: The estimated age weighted seroprevalence of CMV in 20- to 69-year old Australians was 76.12 +/- 0.13%, with higher seroprevalence in females and older age groups. Seroprevalence decreased over the study period, while the demand for CMV-seronegative RBC components increased. It was predicted that component acquisition may be insufficient by FY 2017/18 if current trends persist. CONCLUSION: These findings represent an evaluation of CMV seroepidemiology in Australia and form a basis to predict the future status of CMV-seronegative RBC component inventories. The results will serve to guide Blood Service operations and inform current international debate on CMV-safe blood components. PMID- 26801678 TI - Livedo reticularis following use of norepinephrine (noradrenaline): a case report. PMID- 26801677 TI - Cathodic Voltage-controlled Electrical Stimulation Plus Prolonged Vancomycin Reduce Bacterial Burden of a Titanium Implant-associated Infection in a Rodent Model. AB - BACKGROUND: Cathodic voltage-controlled electrical stimulation (CVCES) of titanium implants, either alone or combined with a short course of vancomycin, has previously been shown to reduce the bone and implant bacterial burden in a rodent model of methicillin-resistant Staphylococcus aureus (MRSA) implant associated infection (IAI). Clinically, the goal is to achieve complete eradication of the IAI; therefore, the rationale for the present study was to evaluate the antimicrobial effects of combining CVCES with prolonged antibiotic therapy with the goal of decreasing the colony-forming units (CFUs) to undetectable levels. QUESTIONS/PURPOSES: (1) In an animal MRSA IAI model, does combining CVCES with prolonged vancomycin therapy decrease bacteria burden on the implant and surrounding bone to undetectable levels? (2) When used with prolonged vancomycin therapy, are two CVCES treatments more effective than one? (3) What are the longer term histologic effects (inflammation and granulation tissue) of CVCES on the surrounding tissue? METHODS: Twenty adult male Long-Evans rats with surgically placed shoulder titanium implants were infected with a clinical strain of MRSA (NRS70). One week after infection, the rats were randomly divided into four groups of five: (1) VANCO: only vancomycin treatment (150 mg/kg, subcutaneous, twice daily for 5 weeks); (2) VANCO + 1STIM: vancomycin treatment (same as the VANCO group) coupled with one CVCES treatment (-1.8 V for 1 hour on postoperative day [POD] 7); (3) VANCO + 2STIM: vancomycin treatment (same as the VANCO group) coupled with two CVCES treatments (-1.8 V for 1 hour on POD 7 and POD 21); or (4) CONT: no treatment. On POD 42, the implant, bone, and peripheral blood were collected for CFU enumeration and histological analysis, where we compared CFU/mL on the implants and bone among the groups. A pathologist, blinded to the experimental conditions, performed a semiquantitative analysis of inflammation and granulation tissue present in serial sections of the humeral head for animals in each experimental group. RESULTS: The VANCO + 1STIM decreased the implant bacterial burden (median = 0, range = 0-10 CFU/mL) when compared with CONT (median = 5.7 * 10(4), range = 4.0 * 10(3)-8.0 * 10(5) CFU/mL; difference of medians = -5.6 * 10(4); p < 0.001) and VANCO (median = 4.9 * 10(3), range = 9.0 * 10(2)-2.1 * 10(4) CFU/mL; difference of medians = -4.9 * 10(3); p < 0.001). The VANCO + 1STIM decreased the bone bacterial burden (median = 0, range = 0-0 CFU/mL) when compared with CONT (median = 1.3 * 10(2), range = 0-9.4 * 10(2) CFU/mL; difference of medians = -1.3 * 10(2); p < 0.001) but was not different from VANCO (median = 0, range = 0-1.3 * 10(2) CFU/mL; difference of medians = 0; p = 0.210). The VANCO + 2STIM group had implant CFU (median = 0, range = 0-8.0 * 10(1) CFU/mL) and bone CFU (median = 0, range = 0-2.0 * 10(1) CFU/mL) that were not different from the VANCO + 1STIM treatment group implant CFU (median = 0, range = 0-10 CFU/mL; difference of medians = 0; p = 0.334) and bone CFU (median = 0, range = 0-0 CFU/mL; difference of medians = 0; p = 0.473). The histological analysis showed no deleterious effects on the surrounding tissue as a result of the treatments. CONCLUSIONS: Using CVCES in combination with prolonged vancomycin resulted in decreased MRSA bacterial burden, and it may be beneficial in treating biofilm-related implant infections. CLINICAL RELEVANCE: CVCES combined with clinically relevant lengths of vancomycin therapy may be a treatment option for IAI and allow for component retention in certain clinical scenarios. However, more animal research and human trials confirming the efficacy of this approach are needed before such a clinical recommendation could be made. PMID- 26801679 TI - Laparoscopic 'ultra' minimally access left colectomy for cancer using 2.9 mm percutaneous instruments and transvaginal specimen extraction--a video vignette. PMID- 26801680 TI - X-linked Charcot-Marie-Tooth disease type 6 (CMTX6) patients with a p.R158H mutation in the pyruvate dehydrogenase kinase isoenzyme 3 gene. AB - Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. Mutations in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene have been found to cause X-linked dominant CMT type 6 (CMTX6). This study identified the p.R158H PDK3 mutation after screening 67 probable X-linked CMT families. The mutation fully segregated with the phenotype, and genotyping the family indicated the mutation arose on a different haplotype compared with the original Australian CMTX6 family. Results of bisulphite sequencing suggest that methylated deamination of a CpG dinucleotide may cause the recurrent p.R158H mutation. The frequency of the p.R158H PDK3 mutation in Koreans is very rare. Magnetic resonance imaging revealed fatty infiltration involving distal muscles in the lower extremities. In addition, fatty infiltrations were predominantly observed in the soleus muscles, with a lesser extent in tibialis anterior muscles. This differs from demyelinating CMT1A patients and is similar to axonal CMT2A patients. The clinical, neuroimaging, and electrophysiological findings from a second CMTX6 family with the p.R158H PDK3 mutation were similar to the axonal neuropathy reported in the Australian family. PMID- 26801683 TI - Incorporating modeling and simulations in undergraduate biophysical chemistry course to promote understanding of structure-dynamics-function relationships in proteins. AB - A project-based biophysical chemistry laboratory course, which is offered to the biochemistry and molecular biology majors in their senior year, is described. In this course, the classroom study of the structure-function of biomolecules is integrated with the discovery-guided laboratory study of these molecules using computer modeling and simulations. In particular, modern computational tools are employed to elucidate the relationship between structure, dynamics, and function in proteins. Computer-based laboratory protocols that we introduced in three modules allow students to visualize the secondary, super-secondary, and tertiary structures of proteins, analyze non-covalent interactions in protein-ligand complexes, develop three-dimensional structural models (homology model) for new protein sequences and evaluate their structural qualities, and study proteins' intrinsic dynamics to understand their functions. In the fourth module, students are assigned to an authentic research problem, where they apply their laboratory skills (acquired in modules 1-3) to answer conceptual biophysical questions. Through this process, students gain in-depth understanding of protein dynamics the missing link between structure and function. Additionally, the requirement of term papers sharpens students' writing and communication skills. Finally, these projects result in new findings that are communicated in peer-reviewed journals. PMID- 26801681 TI - Horizontal Gene Transfer and the History of Life. AB - Microbes acquire DNA from a variety of sources. The last decades, which have seen the development of genome sequencing, have revealed that horizontal gene transfer has been a major evolutionary force that has constantly reshaped genomes throughout evolution. However, because the history of life must ultimately be deduced from gene phylogenies, the lack of methods to account for horizontal gene transfer has thrown into confusion the very concept of the tree of life. As a result, many questions remain open, but emerging methodological developments promise to use information conveyed by horizontal gene transfer that remains unexploited today. PMID- 26801684 TI - DELLA proteins physically interact with CONSTANS to regulate flowering under long days in Arabidopsis. AB - Proper timing of flowering is essential for reproduction of plants. Although it is well known that both light and gibberellin (GA) signaling play critical roles in promoting flowering in Arabidopsis thaliana, whether and how they are integrated to regulate flowering remain largely unknown. Here, we show through biochemical studies that DELLA proteins physically interact with CONSTANS (CO). Furthermore, the interaction of CO with NF-YB2 is inhibited by the DELLA protein, RGA. Our findings suggest that regulation of flowering by GA signaling in leaves under long days is mediated, at least in part, through repression of DELLA proteins on CO, providing a molecular link between DELLA proteins, key components in GA signaling pathway, and CO, a critical flowering activator in photoperiod signaling pathway. PMID- 26801682 TI - Adult Neurogenesis and Psychiatric Disorders. AB - Psychiatric disorders continue to be among the most challenging disorders to diagnose and treat because there is no single genetic or anatomical locus that is causative for the disease. Current treatments are often blunt tools used to ameliorate the most severe symptoms, at the risk of disrupting functional neural systems. There is a critical need to develop new therapeutic strategies that can target circumscribed functional or anatomical domains of pathology. Adult hippocampal neurogenesis may be one such domain. Here, we review the evidence suggesting that adult hippocampal neurogenesis plays a role in emotional regulation and forms of learning and memory that include temporal and spatial memory encoding and context discrimination, and that its dysregulation is associated with psychiatric disorders, such as affective disorders, schizophrenia, and drug addiction. Further, adult neurogenesis has proven to be an effective model to investigate basic processes of neuronal development and converging evidence suggests that aberrant neural development may be an etiological factor, even in late-onset diseases. Constitutive neurogenesis in the hippocampus of the mature brain reflects large-scale plasticity unique to this region and could be a potential hub for modulation of a subset of cognitive and affective behaviors that are affected by multiple psychiatric disorders. PMID- 26801687 TI - Toward elucidation of dioxin-mediated chloracne and Ah receptor functions. AB - Target cells and molecular targets responsible for dioxin-mediated chloracne, the hallmark of dioxin toxicity, are reviewed. The dioxin TCDD accumulates in sebum, and thereby persistently activates the Ah receptor (AhR), expressed in bipotential stem/progenitor cells of the sebaceous gland. AhR operates in cooperation with other transcription factors including c-Myc, Blimp1 and beta Catenin/TCF: c-Myc stimulates exit of stem cells from quiescence to proliferating sebocyte progenitors; Blimp1 is a major c-Myc repressor, and beta-Catenin/TCF represses sebaceous gland differentiation and stimulates differentiation to interfollicular epidermis. TCDD has been demonstrated to induce Blimp1 expression in the sebocyte stem/progenitor cell line SZ95, leading to sebocyte apoptosis and proliferation of interfollicular epidermis cells. These findings explain observations in TCDD-poisoned individuals, and identify target cells and molecular targets of dioxin-mediated chloracne. They clearly demonstrate that the AhR operates in a cell context-dependent manner, and provide hints to homeostatic functions of AhR in stem/progenitor cells. PMID- 26801685 TI - Developmental alcohol exposure leads to a persistent change on astrocyte secretome. AB - Fetal alcohol spectrum disorder is the most common cause of mental disabilities in the western world. It has been quite established that acute alcohol exposure can dramatically affect astrocyte function. Because the effects of early alcohol exposure on cell physiology can persist into adulthood, we tested the hypothesis that ethanol exposure in ferrets during a period equivalent to the last months of human gestation leads to persistent changes in astrocyte secretome in vitro. Animals were treated with ethanol (3.5 g/kg) or saline between postnatal day (P)10-30. At P31, astrocyte cultures were made and cells were submitted to stable isotope labeling by amino acids. Twenty-four hour conditioned media of cells obtained from ethanol- or saline-treated animals (ET-CM or SAL-CM) were collected and analyzed by quantitative mass spectrometry in tandem with liquid chromatography. Here, we show that 65 out of 280 quantifiable proteins displayed significant differences comparing ET-CM to SAL-CM. Among the 59 proteins that were found to be reduced in ET-CM we observed components of the extracellular matrix such as laminin subunits alpha2, alpha4, beta1, beta2, and gamma1 and the proteoglycans biglycan, heparan sulfate proteoglycan 2, and lumican. Proteins with trophic function such as insulin-like growth factor binding protein 4, pigment epithelium-derived factor, and clusterin as well as proteins involved on modulation of proteolysis such as metalloproteinase inhibitor 1 and plasminogen activator inhibitor-1 were also reduced. In contrast, pro-synaptogeneic proteins like thrombospondin-1, hevin as well as the modulator of extracelular matrix expression, angiotensinogen, were found increased in ET-CM. The analysis of interactome maps through ingenuity pathway analysis demonstrated that the amyloid beta A4 protein precursor, which was found reduced in ET-CM, was previously shown to interact with ten other proteins that exhibited significant changes in the ET CM. Taken together our results strongly suggest that early exposure to teratogens such as alcohol may lead to an enduring change in astrocyte secretome. Despite efforts in prevention, fetal alcohol spectrum disorders are a major cause of mental disabilities. Here, we show that developmental exposure to alcohol lead to a persistent change in the pattern of proteins secreted (secretome) by astrocytes. This study is also the first mass spectrometry-based assessment of the astrocyte secretome in a gyrencephalic animal. Cover Image for this issue: doi: 10.1111/jnc.13320. PMID- 26801686 TI - Activation of the MAPK/Akt/Nrf2-Egr1/HO-1-GCLc axis protects MG-63 osteosarcoma cells against 15d-PGJ2-mediated cell death. AB - Despite considerable efforts to improve treatment modalities for osteosarcoma (OS), patient survival remains poor mainly due to pro-survival pathways in OS cells. Among others, prostaglandins (PGs) are the potent regulators of bone homoeostasis and OS pathophysiology. Therefore, the present study aimed to elucidate the impact of 15-deoxy-Delta(12,14)-PGJ2 (15d-PGJ2, a stable PGD2 degradation product) on cell death/cell survival pathways in p53-deficient MG-63 OS cells. Our findings show that 15d-PGJ2 induces generation of reactive oxygen species that promote p38 MAPK activation and subsequent Akt phosphorylation. This pathway induced nuclear expression of Nrf2 and Egr1, and increased transcription of haem oxygenase-1 (HO-1) and the catalytic subunit of glutamate cysteine ligase (GCLc), catalysing the first step in GSH synthesis. Silencing of Nrf2, Egr1 and HO-1 significantly elevated 15d-PGJ2-mediated reduction of cellular metabolic activity. Activation of cell survival genes including HO-1 and GCLc inhibited 15d PGJ2-induced cleavage of pro-caspase-3 and PARP. Annexin V/propidium iodide staining showed an increase in early/late apoptotic cells in response to 15d PGJ2. The observed 15d-PGJ2-mediated signalling events are independent of PGD2 receptors (DP1 and DP2) and PPARgamma. In addition, the electrophilic carbon atom C9 is a prerequisite for the observed activity of 15d-PGJ2. The present data show that the intracellular redox imbalance acted as a node and triggered both death and survival pathways in response to 15d-PGJ2. Pharmacological or genetic interference of the pro-survival pathway, the p38 MAPK/Akt/Nrf2-Egr1/HO-1-GCLc axis, sensitizes MG-63 cells towards 15d-PGJ2-mediated apoptosis. PMID- 26801688 TI - The design of redox active thiol peroxidase mimics: Dihydrolipoic acid recognition correlates with cytotoxicity and prooxidant action. AB - Redox active molecules containing organoselenium or organotellurium groups catalyse the oxidation of cellular thiols by hydrogen peroxide and are currently being developed as therapeutic agents. Potentially these synthetic thiol peroxidase (TPx) mimics can protect cells from oxidative stress by catalysing the reduction of reactive oxygen species by the cellular thiol glutathione, an activity which mimics the function of the antioxidant enzyme glutathione peroxidase. Alternatively they can act as prooxidants by catalysing the oxidation of essential thiol species within the cell. However the structure-activity relationships which determine the choice of thiol substrate, and hence the overall antioxidant or prooxidant outcome of drug administration, remain unknown. We report the first study that relates the pharmacological properties of TPx mimics with their solubility and catalytic activity using different thiol substrates. We used a series of structurally related compounds PhMCnH2n+1 (M=Se, Te; n=4-7) and investigated their ability to catalyse the oxidation of the cellular thiols glutathione and dihydrolipoic acid by hydrogen peroxide. The resulting rate constants (kobs) were then related to compound cytotoxicity and antioxidant versus prooxidant action in A549 cancer cells. The results show that the dihydrolipoic acid kobs values correlate with both cytotoxicity and prooxidant function. This enabled us to define a relationship, IC50=10+280e( 5(DHLA) (kobs)), which allows the prediction of TPx mimic cytotoxicity. In contrast, hydrophobicity and glutathione kobs were unrelated to the compounds' redox pharmacology. PMID- 26801736 TI - Proteomic and peptidomic profiling of Brazilian artisanal 'Coalho' cheese. AB - BACKGROUND: Artisanal 'Coalho' cheese is a product typically popular in the Brazilian north-eastern region. Production of this cheese represents about 9.2% of the internal crude product of Pernambuco State. Several peptides are generated from hydrolysis of alphaS1 -, alphaS2 -, beta-, and kappa-caseins during manufacture of this cheese. The commercial importance of Brazilian artisanal 'Coalho' cheese justifies the examination of both the protein and peptide profiles of cheeses from six cities of the semi-arid region of Pernambuco State, Brazil. RESULTS: SDS-PAGE of the aqueous extracts of 'Coalho' cheeses (WSP) showed bands of lactoferrin, beta-lactoglobulin, beta-lactoglobulin (dimer), alpha-lactoalbumin, bovine serum albumin, alpha-casein, beta-casein, kappa-casein and para-kappa-casein. A total of 57 to 72 peptides were confirmed by mass spectra in the different samples of 'Coalho' cheese which 32 known peptides (11 from alphaS1 -casein, three from alphaS2 -casein, 15 from beta-casein and three from kappa-casein), comprising seven caseinphosphopeptides. Among the unidentified peptides, three showed high intensity peaks in all 'Coalho' cheeses studied (with molecular weights of 1597, 1725/1726, 2778/2779 Da). CONCLUSION: The proteomic studies revealed peptides that may represent molecular markers or fingerprints for investigating the quality control and regional characterisation of these 'Coalho' cheeses. (c) 2016 Society of Chemical Industry. PMID- 26801737 TI - Resensitizing Refractory ALK+ NSCLC: A Case Study. PMID- 26801735 TI - Inhibition of Transforming Growth Factor-beta Activation Diminishes Tumor Progression and Osteolytic Bone Disease in Mouse Models of Multiple Myeloma. AB - Transforming growth factor (TGF)-beta supports multiple myeloma progression and associated osteolytic bone disease. Conversion of latent TGF-beta to its biologically active form is a major regulatory node controlling its activity. Thrombospondin1 (TSP1) binds and activates TGF-beta. TSP1 is increased in myeloma, and TSP1-TGF-beta activation inhibits osteoblast differentiation. We hypothesized that TSP1 regulates TGF-beta activity in myeloma and that antagonism of the TSP1-TGF-beta axis inhibits myeloma progression. Antagonists (LSKL peptide, SRI31277) derived from the LSKL sequence of latent TGF-beta that block TSP1-TGF-beta activation were used to determine the role of the TSP1-TGF-beta pathway in mouse models of myeloma. TSP1 binds to human myeloma cells and activates TGF-beta produced by cultured human and mouse myeloma cell lines. Antagonists delivered via osmotic pump in an intratibial severe combined immunodeficiency CAG myeloma model or in a systemic severe combined immunodeficiency CAG-heparanase model of aggressive myeloma reduced TGF-beta signaling (phospho-Smad 2) in bone sections, tumor burden, mouse IL-6, and osteoclasts, increased osteoblast number, and inhibited bone destruction as measured by microcomputed tomography. SRI31277 reduced tumor burden in the immune competent 5TGM1 myeloma model. SRI31277 was as effective as dexamethasone or bortezomib, and SRI31277 combined with bortezomib showed greater tumor reduction than either agent alone. These studies validate TSP1-regulated TGF-beta activation as a therapeutic strategy for targeted inhibition of TGF-beta in myeloma. PMID- 26801738 TI - Correspondence article regarding CD68 as a marker of CD8+ lymphoid proliferation suggested by Wobser et al. PMID- 26801739 TI - Expressed emotion and the escalation of depressive symptoms in individuals with recent-onset schizophrenia. AB - AIM: This study examined whether expressed emotion (EE) predicts the emergence of depressive symptoms over a 1-year period in 109 individuals with recent-onset schizophrenia. METHODS AND RESULTS: Cox proportional hazards regression analyses indicated that EE did not predict the emergence of depressive symptoms. The results also indicated that the EE factors (criticism, hostility and emotional overinvolvement), when examined individually, also did not predict the emergence of depressive symptoms. CONCLUSIONS: Given the large number of patients in the study who were followed up for 1 year and another study's finding, using a subset of patients from the current study, of a significant relationship between EE and psychotic relapse, the data suggest that whereas EE is related to both psychotic relapse in individuals with recent-onset schizophrenia and depressive relapse in individuals with major depressive disorder, EE does not appear to predict depressive exacerbation in individuals with recent-onset schizophrenia. PMID- 26801740 TI - Immunotherapy using algal-produced Ara h 1 core domain suppresses peanut allergy in mice. AB - Peanut allergy is an IgE-mediated adverse reaction to a subset of proteins found in peanuts. Immunotherapy aims to desensitize allergic patients through repeated and escalating exposures for several months to years using extracts or flours. The complex mix of proteins and variability between preparations complicates immunotherapy studies. Moreover, peanut immunotherapy is associated with frequent negative side effects and patients are often at risk of allergic reactions once immunotherapy is discontinued. Allergen-specific approaches using recombinant proteins are an attractive alternative because they allow more precise dosing and the opportunity to engineer proteins with improved safety profiles. We tested whether Ara h 1 and Ara h 2, two major peanut allergens, could be produced using chloroplast of the unicellular eukaryotic alga, Chlamydomonas reinhardtii. C. reinhardtii is novel host for producing allergens that is genetically tractable, inexpensive and easy to grow, and is able to produce more complex proteins than bacterial hosts. Compared to the native proteins, algal-produced Ara h 1 core domain and Ara h 2 have a reduced affinity for IgE from peanut-allergic patients. We further found that immunotherapy using algal-produced Ara h 1 core domain confers protection from peanut-induced anaphylaxis in a murine model of peanut allergy. PMID- 26801742 TI - A novel NaV1.5 voltage sensor mutation associated with severe atrial and ventricular arrhythmias. AB - BACKGROUND: Inherited autosomal dominant mutations in cardiac sodium channels (NaV1.5) cause various arrhythmias, such as long QT syndrome and Brugada syndrome. Although dozens of mutations throughout the protein have been reported, there are few reported mutations within a voltage sensor S4 transmembrane segment and few that are homozygous. Here we report analysis of a novel lidocaine sensitive recessive mutation, p.R1309H, in the NaV1.5 DIII/S4 voltage sensor in a patient with a complex arrhythmia syndrome. METHODS AND RESULTS: We expressed the wild type or mutant NaV1.5 heterologously for analysis with the patch-clamp and voltage clamp fluorometry (VCF) techniques. p.R1309H depolarized the voltage dependence of activation, hyperpolarized the voltage-dependence of inactivation, and slowed recovery from inactivation, thereby reducing the channel availability at physiologic membrane potentials. Additionally, p.R1309H increased the "late" Na(+) current. The location of the mutation in DIIIS4 prompted testing for a gating pore current. We observed an inward current at hyperpolarizing voltages that likely exacerbates the loss-of-function defects at resting membrane potentials. Lidocaine reduced the gating pore current. CONCLUSIONS: The p.R1309H homozygous NaV1.5 mutation conferred both gain-of-function and loss-of-function effects on NaV1.5 channel activity. Reduction of a mutation-induced gating pore current by lidocaine suggested a therapeutic mechanism. PMID- 26801743 TI - STREAM: Elucidating How Alcohol Use Disorders are Managed in UK General Practice Today. AB - AIMS: To characterize a contemporaneous cohort of UK general practice patients with alcohol use disorder and describe their management. METHODS: Prospective observational study in 25 primary care practices in England and Scotland. Adult patients with known or suspected alcohol dependence (Alcohol Use Disorders Identification Test score >=8) were followed for 6 months and were profiled using baseline data. Changes over time in treatment for alcohol dependence (strategy, goals, modality) and the level of compliance were examined. RESULTS: Targeted case identification was a feasible means of identifying patients with DSM-IV confirmed alcohol dependence in general practice. In the cohort (n = 218), mean total alcohol consumption was high (men: 86.9 g/day; women: 62.7 g/day) and psychiatric co-morbidities were common (depression: 25.8% of patients; anxiety disorders: 25.8% of patients). At baseline, about half of patients reported ongoing or planned treatment for alcohol dependence. Over 6 months' observation, treatment modalities did not change and most patients retained their original stated treatment goal of abstinence or reduced alcohol intake. CONCLUSIONS: Targeted case identification in general practice identifies patients with alcohol use disorder in need of treatment. PMID- 26801741 TI - Polymerase delta-interacting protein 2 regulates collagen accumulation via activation of the Akt/mTOR pathway in vascular smooth muscle cells. AB - OBJECTIVES: Polymerase delta interacting protein 2 (Poldip2) has previously been implicated in migration, proliferation and extracellular matrix (ECM) production in vascular smooth muscle cells. To better understand the role of Poldip2 in ECM regulation, we investigated the mechanism responsible for collagen I accumulation in Poldip2(+/-) mouse aortic smooth muscle cells (MASMs). APPROACH AND RESULTS: Protein degradation and protein synthesis pathways were investigated. Depletion of Poldip2 had no effect on proteasome activity, but caused a partial reduction in autophagic flux. However, the rate of collagen I degradation was increased in Poldip2(+/-) vs. Poldip2(+/+) MASMs. Conversely, activation of the PI3K/Akt/mTOR signaling pathway, involved in regulation of protein synthesis, was significantly elevated in Poldip2(+/-) MASMs as was beta1-integrin expression. Suppressing mTOR signaling using Akt inhibitor or rapamycin and reducing beta1-integrin expression using siRNA prevented the increase in collagen I production. While collagen I and fibronectin were increased in Poldip2(+/-) MASMs, overall protein synthesis was not different from that in Poldip2(+/)(+)MASMs, suggesting selectivity of Poldip2 for ECM proteins. CONCLUSIONS: Poldip2(+/-) MASMs exhibit higher beta1-integrin expression and activity of the PI3K/Akt/mTOR signaling pathway, leading to increased ECM protein synthesis. These findings have important implications for vascular diseases in which ECM accumulation plays a role. PMID- 26801744 TI - Comprehensive annotation of Glossina pallidipes salivary gland hypertrophy virus from Ethiopian tsetse flies: a proteogenomics approach. AB - Glossina pallidipes salivary gland hypertrophy virus (GpSGHV; family Hytrosaviridae) can establish asymptomatic and symptomatic infection in its tsetse fly host. Here, we present a comprehensive annotation of the genome of an Ethiopian GpSGHV isolate (GpSGHV-Eth) compared with the reference Ugandan GpSGHV isolate (GpSGHV-Uga; GenBank accession number EF568108). GpSGHV-Eth has higher salivary gland hypertrophy syndrome prevalence than GpSGHV-Uga. We show that the GpSGHV-Eth genome has 190 291 nt, a low G+C content (27.9 %) and encodes 174 putative ORFs. Using proteogenomic and transcriptome mapping, 141 and 86 ORFs were mapped by transcripts and peptides, respectively. Furthermore, of the 174 ORFs, 132 had putative transcriptional signals [TATA-like box and poly(A) signals]. Sixty ORFs had both TATA-like box promoter and poly(A) signals, and mapped by both transcripts and peptides, implying that these ORFs encode functional proteins. Of the 60 ORFs, 10 ORFs are homologues to baculovirus and nudivirus core genes, including three per os infectivity factors and four RNA polymerase subunits (LEF4, 5, 8 and 9). Whereas GpSGHV-Eth and GpSGHV-Uga are 98.1 % similar at the nucleotide level, 37 ORFs in the GpSGHV-Eth genome had nucleotide insertions (n = 17) and deletions (n = 20) compared with their homologues in GpSGHV-Uga. Furthermore, compared with the GpSGHV-Uga genome, 11 and 24 GpSGHV ORFs were deleted and novel, respectively. Further, 13 GpSGHV-Eth ORFs were non-canonical; they had either CTG or TTG start codons instead of ATG. Taken together, these data suggest that GpSGHV-Eth and GpSGHV-Uga represent two different lineages of the same virus. Genetic differences combined with host and environmental factors possibly explain the differential GpSGHV pathogenesis observed in different G. pallidipes colonies. PMID- 26801747 TI - Medical Students Who Pursue a Joint MD/MBA Degree: Who Are They and Where Are They Heading? AB - Increasingly, health care is being delivered in large, complex organizations, and physicians must learn to function effectively in them. As a result, several medical and business schools have developed joint programs to train physician leaders who receive both medical degree (MD) and master of business administration (MBA) degrees. We examined several themes in relation to these programs, revolving around concerns about who is attracted to them and whether exposure to the differing cultures of medicine and business have an impact on the professional identities of their graduates as manifested in their motivations, aspirations, and careers. We addressed these issues by studying students in the joint MD/MBA program at Harvard Medical School (HMS) and Harvard Business School (HBS). Our data came from several internal sources and a survey of all students enrolled in the joint program in spring 2013. We found relatively few differences between joint program students and equivalent cohorts of HMS students in terms of personal characteristics, preadmission performance, and performance at HMS and HBS. Contrary to the concerns that such programs may draw students away from medicine, the vast majority embraced careers involving extensive postgraduate medical training, with long-term plans that leveraged their new perspectives and skills to improve health care delivery. PMID- 26801745 TI - Uridine homeostatic disorder leads to DNA damage and tumorigenesis. AB - Uridine is a natural nucleoside precursor of uridine monophosphate in organisms and thus is considered to be safe and is used in a wide range of clinical settings. The far-reaching effects of pharmacological uridine have long been neglected. Here, we report that the homeostatic disorder of uridine is carcinogenic. Targeted disruption (-/-) of murine uridine phosphorylase (UPase) disrupted the homeostasis of uridine and increased spontaneous tumorigenesis by more than 3-fold. Multiple tumors (e.g., lymphoma, hepatoma and lung adenoma) occurred simultaneously in some UPase deficient mice, but not in wild-type mice raised under the same conditions. In the tissue from UPase -/- mice, the 2' deoxyuridine,5'-triphosphate (dUTP) levels and uracil DNA were increased and p53 was activated with an increased phospho-Ser18 p53 level. Exposing cell lines (e.g., MCF-7, RKO, HCT-8 and NCI-H460) to uridine (10 or 30 uM) led to uracil DNA damage and p53 activation, which in turn triggered the DNA damage response. In these cells, phospho-ATM, phospho-CHK2, and phospho-gammaH2AX were increased by uridine. These data suggest that uridine homeostatic disorder leads to uracil DNA damage and that pharmacological uridine may be carcinogenic. PMID- 26801746 TI - Overcoming cisplatin resistance of ovarian cancer cells by targeting HIF-1 regulated cancer metabolism. AB - Cisplatin is currently one of the most effective chemotherapeutic drugs used for treating ovarian cancer; however, resistance to cisplatin is common. In this study, we explored an experimental strategy for overcoming cisplatin resistance of human ovarian cancer from the new perspective of cancer cell metabolism. By using two pairs of genetically matched cisplatin-sensitive and cisplatin resistant ovarian cancer cell lines, we tested the hypothesis that downregulating hypoxia-inducible factor-1 (HIF-1), which regulates metabolic enzymes involved in glycolysis, is a promising strategy for overcoming cisplatin resistance of human ovarian cancer cells. We found that cisplatin downregulated the level of the regulatable alpha subunit of HIF-1, HIF-1alpha, in cisplatin-sensitive ovarian cancer cells through enhancing HIF-1alpha degradation but did not downregulate HIF-1alpha in their cisplatin-resistant counterparts. Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. We further demonstrated that knockdown of HIF-1alpha improved the response of cisplatin-resistant ovarian cancer cells to cisplatin by redirecting the aerobic glycolysis in the resistant cancer cells toward mitochondrial oxidative phosphorylation, leading to cell death through overproduction of reactive oxygen species. Our findings suggest that the HIF-1alpha-regulated cancer metabolism pathway could be a novel target for overcoming cisplatin resistance in ovarian cancer. PMID- 26801748 TI - Editorial: Plant and Cell Physiology's 2016 Online Database Issue. PMID- 26801749 TI - Drug companies vow to work more closely with governments to combat antimicrobial resistance. PMID- 26801750 TI - [Visceral vascular surgery]. PMID- 26801751 TI - [Endovascular versus conventional vascular surgery--old-fashioned thinking? Part 2: carotid artery stenosis and peripheral arterial occlusive disease]. AB - Endovascular therapy has widely replaced conventional open vascular surgical reconstruction. For this reason, both techniques were widely considered to be competing approaches. Evidence-based data from randomized prospective trials, meta-analyses and clinical registries, however, demonstrated that both techniques should be used to complement each other. It became increasingly more evident that the use of either procedure depends on the underlying disease and the anatomical conditions, whereby a combination of both (hybrid approach) may be the preferred option in certain situations. This review focuses on the treatment of patients with carotid artery stenosis, intermittent claudication, critical limb ischemia and acute limb ischemia. PMID- 26801752 TI - [Endovascular versus conventional vascular surgery - old-fashioned thinking? Part 1: interventions on the aorta]. AB - Endovascular therapy has widely replaced conventional open vascular surgical reconstruction. For this reason both techniques were widely considered to be competing approaches. Evidence-based data from randomized prospective trials, meta-analyses and clinical registries, however, demonstrated that both techniques should be used to complement each other. It became increasingly more evident that the use of either procedure depends on the underlying disease and the anatomical conditions, whereby a combination of both (hybrid approach) may be the preferred option in certain situations. This review focuses on the treatment of complicated acute type B aortic dissection, descending thoracic aortic aneurysms, thoracoabdominal aortic aneurysms as well as asymptomatic and ruptured abdominal aortic aneurysms. PMID- 26801753 TI - [Minimally invasive surgery and robotic surgery: surgery 4.0?]. AB - Surgery can only maintain its role in a highly competitive environment if results are continuously improved, accompanied by further reduction of the interventional trauma for patients and with justifiable costs. Significant impulse to achieve this goal was expected from minimally invasive surgery and, in particular, robotic surgery; however, a real breakthrough has not yet been achieved. Accordingly, the new strategic approach of cognitive surgery is required to optimize the provision of surgical treatment. A full scale integration of all modules utilized in the operating room (OR) into a comprehensive network and the development of systems with technical cognition are needed to upgrade the current technical environment passively controlled by the surgeon into an active collaborative support system (surgery 4.0). Only then can the true potential of minimally invasive surgery and robotic surgery be exploited. PMID- 26801754 TI - [Management of bleeding and infections in the context of visceral surgery]. AB - Bleeding and vascular infections are serious potential complications during abdominal general surgery. The management of bleeding depends on the extent and localization and can range from the application of hemostatics to vascular sutures, interpositioning and ligatures. The use of prosthetic biomaterials implanted endoluminally or during open reconstruction permits palliation of potentially fatal conditions. The overall incidence of infections involving vascular prostheses is relatively low because of routine antibiotic prophylaxis prior to surgery, refinements in sterilization and packaging of devices and careful adherence to aseptic procedural and surgical techniques. When infections occur detection and definitive therapy of the vascular prosthesis are often delayed and the management is complex and tedious. Infections involving vascular prostheses are difficult to eradicate and in general, surgical therapy is required often coupled with excision of the prosthesis. Keys to success include accurate diagnostics to identify the organism and extent of graft infections, specific long-term antibiotic therapy and well-planned surgical interventions to excise and replace the infected graft and sterilize the local tissue. Regardless of the technique used to eradicate graft infections, success is measured by patient survival, freedom from recurrent infection and patency of revascularization. Even when treatment is successful, the morbidity associated with vascular graft infections is considerable. Aortoenteric fistulas (AEF) are a rare (incidence < 1.5 %) but often fatal complication. Primary diagnosis of AEF remains difficult. Computed tomography (CT) and fluorodeoxyglucose positron emission tomography CT (FDG-PET-CT) are the diagnostic tools of choice. Therapy consists of an urgent individualized interdisciplinary surgical approach with primary axillofemoral bypass and secondary prosthesis explantation or in situ replacement and subsequent bowel resection. Endovascular aortic repair (EVAR) is reserved for primary aortoenteric fistulas in patients with no signs of infection or in emergency cases as a bridging method. PMID- 26801755 TI - [Rectal neuroendocrine tumors: endoscopic therapy]. AB - Clinically detected neuroendocrine neoplasms of the rectum have increased 10- to 30-fold in frequency over the past 45 years in Germany. Endoscopic ultrasonography is the method of choice for exact determination of the size of the tumor, depth of infiltration and detection of local lymph node metastases. Well-differentiated neuroendocrine tumors <= 10.0 mm in size that do not infiltrate the muscularis propria can be endoscopically resected. In the case of lymphatic or blood vessel invasion or spread to lymph nodes, surgical lymph node dissection is indicated. The management of well-differentiated, neuroendocrine rectal tumors 10.1-20 mm in size is still a matter of debate. Old age and multimorbidity favor a conservative endoscopic approach; however, in the case of fit young patients, surgical management has to be considered. For neuroendocrine rectal neoplasms >= 20 mm in size, the risk of metastatic spread increases to 60 80 % indicating that an endoscopic resection is not adequate. Due to the introduction of screening colonoscopy, neuroendocrine rectal tumors are nowadays diagnosed mostly at a prognostically favorable early stage. PMID- 26801756 TI - Selective constraints on protamine 2 in primates and rodents. AB - BACKGROUND: Protamines are sperm nuclear proteins with a crucial role in chromatin condensation. Their function is strongly linked to sperm head morphology and male fertility. Protamines appear to be affected by a complex pattern of selective constraints. Previous studies showed that sexual selection affects protamine coding sequence and expression in rodents. Here we analyze selective constraints and post-copulatory sexual selection acting on protamine 2 (Prm2) gene sequences of 53 species of primates and rodents. We focused on possible differences in selective constraints between these two clades and on the two functional domains of PRM2 (cleaved- and mature-PRM2). We also assessed if and how changes in Prm2 coding sequence may affect sperm head dimensions. RESULTS: The domain of Prm2 that is cleaved off during binding to DNA (cleaved Prm2) was found to be under purifying selection in both clades, whereas the domain that remains bound to DNA (mature-Prm2) was found to be positively selected in primates and under relaxed constraint in rodents. Changes in cleaved Prm2 coding sequence are significantly correlated to sperm head width and elongation in rodents. Contrary to expectations, a significant effect of sexual selection was not found on either domain or clade. CONCLUSIONS: Mature-PRM2 may be free to evolve under less constraint due to the existence of PRM1 as a more conserved and functionally redundant copy. The cleaved-PRM2 domain seems to play an important role in sperm head shaping. However, sexual selection on its sequence may be difficult to detect until it is identified which sperm head phenotype (shape and size) confers advantages for sperm performance in different mammalian clades. PMID- 26801757 TI - Anti-fatigue effect of Amarkand on endurance exercise capacity in rats. AB - BACKGROUND: Amarkand tubers are routinely used by many Indian tribes as a specialized food for health and longevity but so far there is no scientific evidence for their activities. Taxonomically, Amarkand belong to genera Eulophia and Dioscorea. METHODS: In this communication, comparative antifatigue potential of Amarkand was analyzed using forced swimming model in rats and evaluated using biomarkers of physical fatigue. RESULTS: Methanol extracts of tubers of D. bulbifera, E. ochreata, E. leghapanensis and bulbils of D. bulbifera exhibited rich polyphenolic content. D. bulbifera bulbils and E. ochreata significantly prolonged the swimming endurance time. Creatine kinase and urea nitrogen were significantly reduced by treatment of D. bulbifera bulbils and E. ochreata as compared to negative control. D. bulbifera bulbils effectively increased creatine (p < 0.001), lactate dehydrogenase (p < 0.01) and hemoglobin (p < 0.001) compared to negative control. D. bulbifera bulbils and E. ochreata treatments significantly increased glycogen (p < 0.05, p < 0.01) and lowered malondialdehyde levels (p < 0.001) in muscles and in liver tissue compared to negative control. CONCLUSION: These results indicate that a treatment with D. bulbifera bulbils and tubers of E. ochreata facilitates aerobic glucose metabolism and endurance by improving various impairments associated with fatigue. PMID- 26801758 TI - Upregulation of miR-483-3p contributes to endothelial progenitor cells dysfunction in deep vein thrombosis patients via SRF. AB - BACKGROUND: Endothelial progenitor cells (EPCs) contribute to recanalization of deep vein thrombosis (DVT). This study aimed to detect miRNA expression profiles in EPCs from patients with DVT and characterize the role of miRNA in EPCs dysfunction. METHODS: EPCs was isolated from DVT patients and control subjects, and miRNA expression profiles were compared to screen differential miRNAs. The candidate miRNAs were confirmed by RT-PCR analysis. The targets of miRNA were identified by bioinformatics analyses, luciferase reporter assay and gene expression analyses. The apoptosis, migration and tube formation of EPCs were examined by flow cytometry, transwell assay and matrigel tube formation assay. A rat model of venous thrombosis was established as in vivo model. RESULTS: We identified miR-483-3p as a candidate miRNA upregulated in EPCs from DVT patients. By using miR-483-3p agomir and antagomir, we demonstrated that miR-483-3p decreased the migration and tube formation while increased the apoptosis of EPCs. Moreover, we identified serum response factor (SRF) as the target of miR-483-3p, and showed that SRF knockdown decreased the migration and tube formation while increased the apoptosis of EPCs. In addition, miR-483-3p inhibition led to enhanced ability of homing and thrombus resolution of EPCs in rat model of venous thrombosis. CONCLUSIONS: miR-483-3p is upregulated in EPCs from DVT patients, and it targets SRF to decrease EPCs migration and tube formation and increase apoptosis in vitro, while decrease EPCs homing and thrombus resolution in vivo. MiR-483-3p is a potential therapeutic target in DVT treatment. PMID- 26801759 TI - The Active for Life Year 5 (AFLY5) school-based cluster randomised controlled trial: effect on potential mediators. AB - BACKGROUND: Active for life year 5 (AFLY5) is a school-based intervention, based on social cognitive theory, which aims to promote healthy levels of physical activity and healthy eating by improving a child's self-efficacy to make healthy choices, their knowledge of how to make such choices and prompting parents to support their children to make healthy choices. Previously published results showed no effect on the three primary outcomes and beneficial effects on three of nine secondary outcomes (time spent screen-viewing at weekends, consumption of snacks and of high energy drinks). This paper aims to determine the effect of the intervention on potential mediators. METHODS: We conducted a cluster RCT of a school-based intervention, with allocation concealed by use of a remote system. The study was undertaken in the South West of England between 2011 and 2013. Participants were school children who were age 8-9 years at baseline assessment and 9-10 years during the intervention. Potential mediators were assessed at the end of the intervention. The intervention consisted of teacher training, provision of all materials required for lessons and homeworks and written materials for school newsletters and parents. The ten potential mediators were child-reported self-efficacy for physical activity and fruit and vegetable consumption, perceived parental logistic support and modelling for their child's physical activity, parental efforts to limit their child's sedentary behaviour and modelling of healthy fruit and vegetable consumption, together with a knowledge assessment. RESULTS: We successfully recruited 60 schools with over 2,221 children; valid data for the 10 mediators were available for 87 % to 96 % of participants. Three of the ten potential mediators were greater in the intervention, compared with the control group: fruit and vegetable self-efficacy 2.2 units (95 % CI: 0.7 to 3.8), assessed on a scale 26 to 130; child-reported maternal limitation of sedentary behaviour 0.5 (0.1 to 0.8), scale 4 to 16; and knowledge 0.5 (0.2, 0.7) scale 0 to 9. Reported maternal limitation of sedentary behaviour and the child's knowledge explained 23 % of the effect of the intervention on reducing time spent on sedentary behaviour at the weekend. There was no effect on other mediators. CONCLUSIONS: Our findings suggest that the effect of the AFLY5 intervention on reducing screen-viewing at weekends was partially mediated by an effect on mothers limiting their child's time spent sedentary and on increasing the child's knowledge about healthy behaviour. However, overall our findings suggest that theory driven interventions, like AFLY5, can fail to influence most potential mediators and this may explain the failure of the intervention to improve most primary and secondary outcomes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN50133740. Registered 17/03/2011. PMID- 26801761 TI - Characterization of Sarcoptes scabiei cofilin gene and assessment of recombinant cofilin protein as an antigen in indirect-ELISA for diagnosis. AB - BACKGROUND: Scabies impairs the health of humans and animals and causes heavy economic losses. Traditional diagnostic methods for scabies are inefficient and ineffective, and so far there is no commercial immunodiagnostic or molecular based test for scabies. METHODS: Here, we used recombinant Sarcoptes scabiei cofilin protein as an antigen to establish indirect ELISA. S. scabiei cofilin is highly homologous to Dermatophagoides farinae Der f 31 allergen (90% identity). The S. scabiei cofilin gene was cloned and expressed in Escherichia coli to obtain recombinant protein. Western blotting and fluorescence immunohistochemistry were carried out, and we established an indirect ELISA method and detected 33 serum samples from scabies infected rabbits and 30 serum samples from naive rabbits. RESULTS: Western blotting demonstrated that S. scabiei cofilin possessed good immunogenicity and fluorescence immunohistochemistry showed the S. scabiei cofilin is widespread in the splanchnic area of mites. In ELISA, a cut-off value of 0.188 was determined to judge experimental positive and negative serum values. Specificity and sensitivity of the ELISA were 87.9 and 83.33%, respectively. CONCLUSIONS: Recombinant S. scabiei cofilin showed potential value as a diagnostic antigen. The ELISA method established could be used in clinical diagnosis and provide experimental information in minimal or asymptomatic infection. PMID- 26801760 TI - Novel c-Met inhibitor suppresses the growth of c-Met-addicted gastric cancer cells. AB - BACKGROUND: c-Met signaling has been implicated in oncogenesis especially in cells with c-met gene amplification. Since 20 % of gastric cancer patients show high level of c-Met expression, c-Met has been identified as a good candidate for targeted therapy in gastric cancer. Herein, we report our newly synthesized c-Met inhibitor by showing its efficacy both in vitro and in vivo. METHODS: Compounds with both triazolopyrazine and pyridoxazine scaffolds were synthesized and tested using HTRF c-Met kinase assay. We performed cytotoxic assay, cellular phosphorylation assay, and cell cycle assay to investigate the cellular inhibitory mechanism of our compounds. We also conducted mouse xenograft assay to see efficacy in vivo. RESULTS: KRC-00509 and KRC-00715 were selected as excellent c-Met inhibitors through biochemical assay, and exhibited to be exclusively selective to c-Met by kinase panel assay. Cytotoxic assays using 18 gastric cancer cell lines showed our c-Met inhibitors suppressed specifically the growth of c-Met overexpressed cell lines, not that of c-Met low expressed cell lines, by inducing G1/S arrest. In c-met amplified cell lines, c-Met inhibitors reduced the downstream signals including Akt and Erk as well as c-Met activity. In vivo Hs746T xenograft assay showed KRC-00715 reduced the tumor size significantly. CONCLUSIONS: Our in vitro and in vivo data suggest KRC-00715 is a potent and highly selective c-Met inhibitor which may have therapeutic potential in gastric tumor with c-Met overexpression. PMID- 26801762 TI - Development of South Australian-Victorian Prostate Cancer Health Outcomes Research Dataset. AB - BACKGROUND: Prostate cancer is the most commonly diagnosed and prevalent malignancy reported to Australian cancer registries, with numerous studies from single institutions summarizing patient outcomes at individual hospitals or States. In order to provide an overview of patterns of care of men with prostate cancer across multiple institutions in Australia, a specialized dataset was developed. This dataset, containing amalgamated data from South Australian and Victorian prostate cancer registries, is called the South Australian-Victorian Prostate Cancer Health Outcomes Research Dataset (SA-VIC PCHORD). RESULTS: A total of 13,598 de-identified records of men with prostate cancer diagnosed and consented between 2008 and 2013 in South Australia and Victoria were merged into the SA-VIC PCHORD. SA-VIC PCHORD contains detailed information about socio demographic, diagnostic and treatment characteristics of patients with prostate cancer in South Australia and Victoria. Data from individual registries are available to researchers and can be accessed under individual data access policies in each State. CONCLUSIONS: The SA-VIC PCHORD will be used for numerous studies summarizing trends in diagnostic characteristics, survival and patterns of care in men with prostate cancer in Victoria and South Australia. It is expected that in the future the SA-VIC PCHORD will become a principal component of the recently developed bi-national Australian and New Zealand Prostate Cancer Outcomes Registry to collect and report patterns of care and standardised patient reported outcome measures of men nation-wide in Australia and New Zealand. PMID- 26801763 TI - NBS-LRR-mediated resistance triggered by aphids: viruses do not adapt; aphids adapt via different mechanisms. AB - BACKGROUND: Aphids are serious pest on crops. By probing with their stylets, they interact with the plant, they vector viruses and when they reach the phloem they start a continuous ingestion. Many plant resistances to aphids have been identified, several have been deployed. However, some resistances breaking down have been observed. In the melon, a gene that confers resistance to aphids has been deployed in some melon-producing areas, and aphid colony development on Vat carrying plants has been observed in certain agrosystems. The Vat gene is a NBS LRR gene that confers resistance to the aphid species Aphis gossypii and exhibits the unusual characteristic of also conferring resistance to non-persistently transmitted viruses when they are inoculated by the aphid. Thus, we characterized patterns of resistance to aphid and virus using the aphid diversity and we investigated the mechanisms by which aphids and viruses may adapt to the Vat gene. RESULTS: Using a Vat-transgenic line built in a susceptible background, we described the Vat- spectrum of resistance to aphids, and resistance to viruses triggered by aphids using a set of six A. gossypii biotypes. Discrepancies between both resistance phenotypes revealed that aphid adaptation to Vat-mediated resistance does not occur only via avirulence factor alterations but also via adaptation to elicited defenses. In experiments conducted with three virus species serially inoculated by aphids from and to Vat plants, the viruses did not evolve to circumvent Vat-mediated resistance. We confirmed discrepancies between both resistance phenotypes by testing each aphid biotype with a set of thirteen melon accessions chosen to reflect the natural diversity of the melon. Inheritance studies revealed that patterns of resistance to virus triggered by aphids are controlled by different alleles at the Vat locus and at least another locus located at a short genetic distance. Therefore, resistance to viruses triggered by aphids is controlled by a gene cluster. CONCLUSIONS: Under the Flor model, changes in the avirulence gene determine the ability of the pathogen to overcome the resistance conferred by a plant gene. The Vat gene belongs to a resistance gene family that fits this pest/pathogen-plant interaction, and we revealed an additional mechanism of aphid adaptation that potentially exists in other interactions between plants and pests or pathogens. PMID- 26801764 TI - Semantic representation of reported measurements in radiology. AB - BACKGROUND: In radiology, a vast amount of diverse data is generated, and unstructured reporting is standard. Hence, much useful information is trapped in free-text form, and often lost in translation and transmission. One relevant source of free-text data consists of reports covering the assessment of changes in tumor burden, which are needed for the evaluation of cancer treatment success. Any change of lesion size is a critical factor in follow-up examinations. It is difficult to retrieve specific information from unstructured reports and to compare them over time. Therefore, a prototype was implemented that demonstrates the structured representation of findings, allowing selective review in consecutive examinations and thus more efficient comparison over time. METHODS: We developed a semantic Model for Clinical Information (MCI) based on existing ontologies from the Open Biological and Biomedical Ontologies (OBO) library. MCI is used for the integrated representation of measured image findings and medical knowledge about the normal size of anatomical entities. An integrated view of the radiology findings is realized by a prototype implementation of a ReportViewer. Further, RECIST (Response Evaluation Criteria In Solid Tumors) guidelines are implemented by SPARQL queries on MCI. The evaluation is based on two data sets of German radiology reports: An oncologic data set consisting of 2584 reports on 377 lymphoma patients and a mixed data set consisting of 6007 reports on diverse medical and surgical patients. All measurement findings were automatically classified as abnormal/normal using formalized medical background knowledge, i.e., knowledge that has been encoded into an ontology. A radiologist evaluated 813 classifications as correct or incorrect. All unclassified findings were evaluated as incorrect. RESULTS: The proposed approach allows the automatic classification of findings with an accuracy of 96.4 % for oncologic reports and 92.9 % for mixed reports. The ReportViewer permits efficient comparison of measured findings from consecutive examinations. The implementation of RECIST guidelines with SPARQL enhances the quality of the selection and comparison of target lesions as well as the corresponding treatment response evaluation. CONCLUSIONS: The developed MCI enables an accurate integrated representation of reported measurements and medical knowledge. Thus, measurements can be automatically classified and integrated in different decision processes. The structured representation is suitable for improved integration of clinical findings during decision-making. The proposed ReportViewer provides a longitudinal overview of the measurements. PMID- 26801765 TI - Beyond the passive interactions at the nano-bio interface: evidence of Cu metalloprotein-driven oxidative dissolution of silver nanoparticles. AB - BACKGROUND: In a biological system, an engineered nanomaterial (ENM) surface is altered by adsorbed proteins that modify ENM fate and toxicity. Thus far, protein corona characterizations have focused on protein adsorption, interaction strength, and downstream impacts on cell interactions. Given previous reports of Ag ENM disruption of Cu trafficking, this study focuses on Ag ENM interactions with a model Cu metalloprotein, Cu(II) azurin. The study provides evidence of otherwise overlooked ENM-protein chemical reactivity within the corona: redox activity. RESULTS: Citrate-coated Ag ENMs of various sizes (10-40 nm) reacted with Cu(II) azurin resulted in an order of magnitude more dissolved ionic silver (Ag(I)(aq)) than samples of Ag ENMs only, ENMs mixed Cu(II) ions, or control proteins such as cytochrome c and horse radish peroxidase. This dramatic increase in ENM oxidative dissolution was observed even when Cu(II) azurin was combined with a diverse mixture of Escherchia coli proteins to mimic the complexity of the cellular conona. SDS PAGE results confirm that the multiprotein ENM corona includes azurin. A Cu(I)(aq) colorimetric indicator confirms Cu(II) azurin reduction upon interaction with Ag ENMs, but not with the addition of ionic silver, Ag(I)(aq). CONCLUSIONS: Cu(II) azurin and 10-40 nm Ag ENMs react to catalyze Ag ENM oxidative dissolution and reduction of the model Cu metalloprotein. Results push the current evaluation of protein-ENM characterization beyond passive binding interactions and enable the proposal of a mechanism for reactivity between a model Cu metalloprotein and Ag ENMs. PMID- 26801766 TI - Erratum to: Lifestyle choices and mental health: a representative population survey. PMID- 26801767 TI - Therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in northwest Benin. AB - BACKGROUND: Artemether/lumefantrine (Coartem((r))) has been used as a treatment for uncomplicated Plasmodium falciparum infection since 2004 in Benin. This open label, non-randomized study evaluated efficacy of artemether-lumefantrine (AL) in treatment of uncomplicated falciparum malaria in children aged 6-59 months in two malaria transmission sites in northwest Benin. METHODS: A 42-day therapeutic efficacy study was conducted between August and November 2014, in accordance with 2009 WHO guidelines. One-hundred and twenty-three children, aged 6 months to 5 years, with uncomplicated falciparum malaria were recruited into the study. The primary endpoint was parasitological cure on day 28 and day 42 while the secondary endpoints included: parasite and fever clearance, improvement in haemoglobin levels. Outcomes were classified as early treatment failure (ETF), late clinical failure, late parasitological failure, and adequate clinical and parasitological response (ACPR). RESULTS: Before PCR correction, ACPR rates were 87% (95 % CI 76.0-94.7) and 75.6%, respectively (95% CI 67.0-82.9) on day 28 and day 42. In each study site, ACPR rates were 78.3% in Djougou and 73% in Cobly on day 42. There was no ETF and after PCR correction ACPR was 100% in study population. All treatment failures were shown to be due to new infections. Fever was significantly cleared in 24 h and approximately 90% of parasites where cleared on day 1 and almost all parasites were cleared on day 2. Haemoglobin concentration showed a slight increase with parasitic clearance. CONCLUSION: AL remains an efficacious drug for the treatment of uncomplicated falciparum malaria in Benin, although higher rates of re-infection remain a concern. Surveillance needs to be continued to detect future changes in parasite sensitivity to artemisinin-based combination therapy. PMID- 26801770 TI - A computing platform to map ecological metabolism by integrating functional mapping and the metabolic theory of ecology. AB - Whole-organism metabolic rate co-varies allometrically with body mass, and is also affected by temperature through different biochemical mechanisms. Here we implement a computational platform to map specific quantitative trait loci (QTLs) that govern the dependence of metabolic rate on size and temperature. The model was formulated within settings of genetic mapping or genome-wide association studies through a mapping population genotyped by a set of molecular markers throughout the genome and phenotyped for metabolic parameters over a range of temperature. The model, estimated by a maximum-likelihood approach, allows a genome-wide search for the underlying metabolic QTLs and the estimation of genotype-specific parameters that specify the metabolism of an organism. Our model provides a tool to detect pleiotropy and epistasis that cause the size- and temperature-dependent change of metabolic rate. PMID- 26801769 TI - Making authentic science accessible-the benefits and challenges of integrating bioinformatics into a high-school science curriculum. AB - Despite the central place held by bioinformatics in modern life sciences and related areas, it has only recently been integrated to a limited extent into high school teaching and learning programs. Here we describe the assessment of a learning environment entitled 'Bioinformatics in the Service of Biotechnology'. Students' learning outcomes and attitudes toward the bioinformatics learning environment were measured by analyzing their answers to questions embedded within the activities, questionnaires, interviews and observations. Students' difficulties and knowledge acquisition were characterized based on four categories: the required domain-specific knowledge (declarative, procedural, strategic or situational), the scientific field that each question stems from (biology, bioinformatics or their combination), the associated cognitive-process dimension (remember, understand, apply, analyze, evaluate, create) and the type of question (open-ended or multiple choice). Analysis of students' cognitive outcomes revealed learning gains in bioinformatics and related scientific fields, as well as appropriation of the bioinformatics approach as part of the students' scientific 'toolbox'. For students, questions stemming from the 'old world' biology field and requiring declarative or strategic knowledge were harder to deal with. This stands in contrast to their teachers' prediction. Analysis of students' affective outcomes revealed positive attitudes toward bioinformatics and the learning environment, as well as their perception of the teacher's role. Insights from this analysis yielded implications and recommendations for curriculum design, classroom enactment, teacher education and research. For example, we recommend teaching bioinformatics in an integrative and comprehensive manner, through an inquiry process, and linking it to the wider science curriculum. PMID- 26801771 TI - The Mesoamerican nephropathy: a regional epidemic of chronic kidney disease? PMID- 26801768 TI - Gene expression profiling in necrotizing enterocolitis reveals pathways common to those reported in Crohn's disease. AB - BACKGROUND: Necrotizing enterocolitis (NEC) is the most frequent life-threatening gastrointestinal disease experienced by premature infants in neonatal intensive care units. The challenge for neonatologists is to detect early clinical manifestations of NEC. One strategy would be to identify specific markers that could be used as early diagnostic tools to identify preterm infants most at risk of developing NEC or in the event of a diagnostic dilemma of suspected disease. As a first step in this direction, we sought to determine the specific gene expression profile of NEC. METHODS: Deep sequencing (RNA-Seq) was used to establish the gene expression profiles in ileal samples obtained from preterm infants diagnosed with NEC and non-NEC conditions. Data were analyzed with Ingenuity Pathway Analysis and ToppCluster softwares. RESULTS: Data analysis indicated that the most significant functional pathways over-represented in NEC neonates were associated with immune functions, such as altered T and B cell signaling, B cell development, and the role of pattern recognition receptors for bacteria and viruses. Among the genes that were strongly modulated in neonates with NEC, we observed a significant degree of similarity when compared with those reported in Crohn's disease, a chronic inflammatory bowel disease. CONCLUSIONS: Gene expression profile analysis revealed a predominantly altered immune response in the intestine of NEC neonates. Moreover, comparative analysis between NEC and Crohn's disease gene expression repertoires revealed a surprisingly high degree of similarity between these two conditions suggesting a new avenue for identifying NEC biomarkers. PMID- 26801772 TI - The Effectiveness of an Educational Brochure as a Risk Minimization Activity to Communicate Important Rare Adverse Events to Health-Care Professionals. AB - INTRODUCTION: Educational brochures are an important tool for communicating risk to health-care professionals. It is important to evaluate the impact of any risk minimization tool to understand the effectiveness of the strategy. The objective of this study was to assess the effectiveness (i.e., respondents' awareness and understanding of the communication) of a targeted educational brochure distributed to health-care professionals (HCPs) as a risk minimization strategy for the communication of new rare and important adverse events (AEs). METHODS: A prospective, non-interventional, online survey was performed following distribution of a specifically designed brochure highlighting new and important adverse events to a targeted HCP population, consisting of known users of the target medicine, as represented by a commercial database. Predefined multiple choice survey questions assessed overall HCP awareness of the brochure and understanding and retention of information in those HCPs who reported receiving the brochure. RESULTS: The educational brochure was sent to a total of 565 HCPs; 121 (21.4%) responded to the survey. The majority of respondents (95.0%) had previously prescribed or dispensed the target medicine. In all, 88 (72.7%) respondents said they had received the educational brochure, of whom 95.5% stated they had at least scanned the main points. More participants who had received the brochure (86.4% to 96.6%) answered the five individual survey questions correctly compared with those who did not (51.5% to 97.0%); this was significant for four out of five questions (P <= 0.005). Significantly more HCPs who received the brochure achieved the predefined pass rate (at least four of five questions answered correctly) compared with HCPs who did not receive the brochure (93.2% vs 57.6%, respectively; P = 0.000003). CONCLUSIONS: Distribution of targeted educational brochures may be an effective risk minimization strategy to raise HCP awareness of new rare and important AEs; educational brochures may also be an effective channel for sharing information on how these AEs can be best managed and on the importance and means of reporting AEs. FUNDING: Celgene Pty Ltd, Melbourne, Australia. PMID- 26801773 TI - Novel homozygous BMP9 nonsense mutation causes pulmonary arterial hypertension: a case report. AB - BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare, progressive, fatal vascular disorder. Genetic predisposition plays vital roles in the development of PAH, with most mutations being identified in genes involved in the transforming growth factor beta (TGF-beta) signaling pathways. Defects in the BMP9 gene have been documented in hereditary hemorrhagic telangiectasia (HHT), the most common inherited vascular disorder, which is occasionally associated with PAH. Selective enhancement of endothelial BMPR2 with BMP9 reverses pulmonary arterial hypertension. CASE PRESENTATION: We report the case of a 5-year-old Hispanic boy who was diagnosed with severe PAH and right heart failure at 3 years of age. During his stay in the pediatric intensive care unit, treatment was initiated with inhaled nitric oxide and intravenous epoprostenol; he subsequently was transitioned to treprostinil, sildenafil, and prophylactic enoxaparin. Now, two years later, the child is asymptomatic on sildenafil, bosentan, subcutaneous treprostinil, and warfarin. Genetic screening revealed a novel homozygous nonsense mutation in the BMP9 gene (c.76C > T; p.Gln26Ter). The child had no telangiectasias or arteriovenous malformations; family history also was negative. Subsequent parental testing showed both parents were heterozygous for the same mutation, indicating that the child inherited the BMP9 mutant allele from each parent. CONCLUSION: To our knowledge, this is the first report of a BMP9 mutation in a patient with PAH. The homozygous nonsense mutation may account for the early onset and severity of PAH in this patient and also fit the 'two-hit' model we proposed previously. The absence of clinical symptoms for PAH in the parents may be due to incomplete penetrance or various expressivities of the BMP9 mutations. Our study expands the spectrum of phenotypes related to BMP9 mutations. PMID- 26801774 TI - Rare Primary Central Nervous System Tumors Encountered in Pediatrics. AB - As part of the special issue on Pediatric Neuro-Oncology, this article will focus on 4 of the rarer tumors in this spectrum, including atypical teratoid rhabdoid tumors, embryonal tumors with multilayered rosettes, choroid plexus tumors, and pleomorphic xanthoastrocytoma. Incidence and current understanding of the molecular pathogenesis of these tumors are discussed, and avenues of therapy both current and prospective are explored. PMID- 26801776 TI - How Are Child Restricted and Repetitive Behaviors Associated with Caregiver Stress Over Time? A Parallel Process Multilevel Growth Model. AB - The impact of raising a child with autism spectrum disorder (ASD) is frequently accompanied by elevated caregiver stress. Examining the variables that predict these elevated rates will help us understand how caregiver stress is impacted by and impacts child behaviors. This study explored how restricted and repetitive behaviors (RRBs) contributed concurrently and longitudinally to caregiver stress in a large sample of preschoolers with ASD using parallel process multilevel growth models. Results indicated that initial rates of and change in RRBs predicted fluctuations in caregiver stress over time. When caregivers reported increased child RRBs, this was mirrored by increases in caregiver stress. Our data support the importance of targeted treatments for RRBs as change in this domain may lead to improvements in caregiver wellbeing. PMID- 26801775 TI - The identification of additional zebrafish DICP genes reveals haplotype variation and linkage to MHC class I genes. AB - Bony fish encode multiple multi-gene families of membrane receptors that are comprised of immunoglobulin (Ig) domains and are predicted to function in innate immunity. One of these families, the diverse immunoglobulin (Ig) domain containing protein (DICP) genes, maps to three chromosomal loci in zebrafish. Most DICPs possess one or two Ig ectodomains and include membrane-bound and secreted forms. Membrane-bound DICPs include putative inhibitory and activating receptors. Recombinant DICP Ig domains bind lipids with varying specificity, a characteristic shared with mammalian CD300 and TREM family members. Numerous DICP transcripts amplified from different lines of zebrafish did not match the zebrafish reference genome sequence suggesting polymorphic and haplotypic variation. The expression of DICPs in three different lines of zebrafish has been characterized employing PCR-based strategies. Certain DICPs exhibit restricted expression in adult tissues whereas others are expressed ubiquitously. Transcripts of a subset of DICPs can be detected during embryonic development suggesting roles in embryonic immunity or other developmental processes. Transcripts representing 11 previously uncharacterized DICP sequences were identified. The assignment of two of these sequences to an unplaced genomic scaffold resulted in the identification of an alternative DICP haplotype that is linked to a MHC class I Z lineage haplotype on zebrafish chromosome 3. The linkage of DICP and MHC class I genes also is observable in the genomes of the related grass carp (Ctenopharyngodon idellus) and common carp (Cyprinus carpio) suggesting that this is a shared character with the last common Cyprinidae ancestor. PMID- 26801777 TI - Children with Autism Detect Targets at Very Rapid Presentation Rates with Similar Accuracy as Adults. AB - Enhanced perception may allow for visual search superiority by individuals with Autism Spectrum Disorder (ASD), but does it occur over time? We tested high functioning children with ASD, typically developing (TD) children, and TD adults in two tasks at three presentation rates (50, 83.3, and 116.7 ms/item) using rapid serial visual presentation. In the Color task, participants detected a purple target letter amongst black letter distractors. In the Category task, participants detected a letter amongst number distractors. Slower rates resulted in higher accuracy. Children with ASD were more accurate than TD children and similar to adults at the fastest rate when detecting color-marked targets, indicating atypical neurodevelopment in ASD may cause generalized perceptual enhancement relative to typically developing peers. PMID- 26801778 TI - Synchronous presentation of invasive ductal carcinoma and mantle cell lymphoma: a diagnostic challenge in menopausal patients. AB - Synchronous presentation of breast carcinoma and non-Hodgkin lymphoma (NHL) is a rare occurrence (Bradford PT, Freedman DM, Goldstein AM, Tucker MA. Increased risk of second primary cancers after a diagnosis of melanoma. Arch Dermatol 2010; 146: :265-72; Dutta Roy S, Stafford JA, Scally J, Selvachandran SN. A rare case of breast carcinoma co-existing with axillary mantle cell lymphoma. World J Surg Oncol 2003; 1: :27; Suresh Attili VS, Dadhich HK, Rao CR, Bapsy PP, Batra U, Anupama G et al. A case of breast cancer coexisting with B-cell follicular lymphoma. Austral Asian J Cancer 2007; 6: :155-6). In particular, only two reported cases on synchronous presentation of invasive ductal carcinoma (IDC) and mantle cell lymphoma (MCL) exist in the English literature. Owing to the rarity, there is a lack of consensus about underlying mechanism as well as optimal treatment strategy, and diagnosing both malignancies together without a delay remains a complex clinical challenge. We report a case of synchronous presentation of IDC and MCL in a 67-year-old female patient whose MCL diagnosis was delayed due to a misinterpretation of her B symptoms as postmenopausal, with a review of the literature on concurrently occurring breast carcinoma and NHL. PMID- 26801779 TI - Tablet/Capsule Size Variation Among the Most Commonly Prescribed Medications for Children in the USA: Retrospective Review and Firsthand Pharmacy Audit. AB - INTRODUCTION: Children are frequently asked to take tablets and capsules of different sizes and shapes to manage acute and chronic medical conditions. Medication size is an important factor that contributes to compliance, yet few studies detail size variation or pediatric pharmacy inventory. OBJECTIVE: This study assesses the available sizes and size variations of common inpatient and outpatient pediatric medications and provides an inventory of the tablet and capsule sizes available in a children's inpatient hospital pharmacy. METHODS: We derived the most frequently prescribed oral medications from US national databases, including the IMS, Vector One((r)): National (VONA) and Pediatric Health Information System (PHIS). We analyzed a composite list using the National Library of Medicine Pillbox website, which provides size measurements. Medications from a children's inpatient pharmacy were audited and hand measured for comparison. RESULTS: We created a list of the top 15 most prescribed inpatient and outpatient pediatric tablet/capsule medications and observed a wide variation in size: acetaminophen 500 mg ranged from 5 to 22 mm in length, median 15 mm. Common pediatric antibiotics were larger and ranged from 8 to 25 mm in length, median 17 mm. Hand-measured samples from the inpatient pharmacy were often the larger pill sizes, despite smaller alternatives being available. CONCLUSIONS: We observed a marked variation in the sizes of common pediatric tablet/capsule medications, and pharmacies that serve children may not stock the most child-friendly medications. Tablet/capsule size does not appear to be considered when decisions about tablet and capsule medication selections are made. These results should increase awareness of these sizes and affect how physicians prescribe, how pharmacies order inventory, and how insurers and pharmaceutical companies pay for and produce pediatric medications. PMID- 26801780 TI - Editor Note. PMID- 26801781 TI - Analysis of the genome sequence of infectious hematopoietic necrosis virus HLJ-09 in China. AB - Infectious hematopoietic necrosis virus (IHNV) is a highly contagious disease of juvenile salmonid fish. Six genome target fragments of the complete genome sequence of IHNV HLJ-09 were amplified by RT-PCR, and the 3'-terminal and 5' terminal region of the genomic RNA were amplified using the RACE method. The complete genome sequence of HLJ-09 comprises 11,132 nucleotides (nt) (Accession number JX649101) and is different from that of other IHNV strains published in GenBank. Homology comparison and phylogenetic analysis of six ORF sequences were carried out using HLJ-09 and other IHNV strains published in GenBank. From phylogenetic tree analysis, the N gene, M gene, and P gene had the closest genetic relationship to IHNV-PRT from Korea. Phylogenetic analysis for the full length of the G gene showed that the HLJ-09 strain exhibited very close homology to the ChYa07, RtNag96, RtUi02, and RtGu01 strains from Korea and Japan, indicating that the HLJ-09 strain belonged to the genotype JRt. Ultimately, the Chinese IHNV HLJ-09 strain may have originated in Korea and Japan. PMID- 26801782 TI - Erratum to: The minimal clinically important difference in the Oxford knee score and Short Form 12 score after total knee arthroplasty. PMID- 26801783 TI - Surgical accuracy in high tibial osteotomy: coronal equivalence of computer navigation and gap measurement. AB - PURPOSE: Medial opening wedge high tibial osteotomy (MOW HTO) is now a successful operation with a range of indications, requiring an individualised approach to the choice of intended correction. This manuscript introduces the concept of surgical accuracy as the absolute deviation of the achieved correction from the intended correction, where small values represent greater accuracy. Surgical accuracy is compared in a randomised controlled trial (RCT) between gap measurement and computer navigation groups. METHODS: This was a prospective RCT conducted over 3 years of 120 consecutive patients with varus malalignment and medial compartment osteoarthritis, who underwent MOW HTO. All procedures were planned with digital software. Patients were randomly assigned into gap measurement or computer navigation groups. Coronal plane alignment was judged using the mechanical tibiofemoral angle (mTFA), before and after surgery. Absolute (positive) values were calculated for surgical accuracy in each individual case. RESULTS: There was no significant difference in the mean intended correction between groups. The achieved mTFA revealed a small under correction in both groups. This was attributed to a failure to account for saw blade thickness (gap measurement) and over-compensation for weight bearing (computer navigation). Surgical accuracy was 1.7 degrees +/- 1.2 degrees (gap measurement) compared to 2.1 degrees +/- 1.4 degrees (computer navigation) without statistical significance. The difference in tibial slope increases of 2.7 degrees +/- 3.9 degrees (gap measurement) and 2.1 degrees +/- 3.9 degrees (computer navigation) had statistical significance (P < 0.001) but magnitude (0.6 degrees ) without clinical relevance. CONCLUSION: Surgical accuracy as described here is a new way to judge achieved alignment following knee osteotomy for individual cases. This work is clinically relevant because coronal surgical accuracy was not superior in either group. Therefore, the increased expense and surgical time associated with navigated MOW HTO is not supported, because meticulously conducted gap measurement yields equivalent surgical accuracy. LEVEL OF EVIDENCE: I. PMID- 26801784 TI - Genetic Counselors in Startup Companies: Redefining the Genetic Counselor Role. AB - Genetic counselors (GCs) have recently begun moving into non-clinic based roles in increasing numbers. A relatively new role for GCs is working for startup companies. Startups are newly established companies in the phase of developing and researching new scalable businesses. This article explores the experiences of four GCs working at different startup companies and aims to provide resources for GCs interested in learning more about these types of roles. The article describes startup culture, including a relatively flat organizational structure, quick product iterations, and flexibility, among other unique cultural characteristics. Financial considerations are described, including how to understand and evaluate a company's financial status, along with a brief explanation of alternate forms of compensation including stock options and equity. Specifically, the article details the uncertainties and rewards of working in a fast-paced startup environment that affords opportunities to try new roles and use the genetic counseling skill set in new ways. This article aims to aid GCs in determining whether a startup environment would be a good fit, learning how to evaluate a specific startup, and understanding how to market themselves for positions at startups. PMID- 26801785 TI - Mind the Gap? An Intensive Longitudinal Study of Between-Person and Within-Person Intention-Behavior Relations. AB - BACKGROUND: Despite their good intentions, people often do not eat healthily. This is known as the intention-behavior gap. Although the intention-behavior relationship is theorized as a within-person process, most evidence is based on between-person differences. PURPOSE: The purpose of the present study is to investigate the within-person intention-behavior association for unhealthy snack consumption. METHODS: Young adults (N = 45) participated in an intensive longitudinal study. They reported intentions and snack consumption five times daily for 7 days (n = 1068 observations analyzed). RESULTS: A within-person unit difference in intentions was associated with a halving of the number of unhealthy snacks consumed in the following 3 h (CI95 27-70 %). Between-person differences in average intentions did not predict unhealthy snack consumption. CONCLUSIONS: Consistent with theory, the intention-behavior relation for healthy eating is best understood as a within-person process. Interventions to reduce unhealthy snacking should target times of day when intentions are weakest. PMID- 26801787 TI - A medial to lateral approach offers a superior lymph node harvest for laparoscopic right colectomy. AB - PURPOSE: Studies have shown improved survival with increasing amounts of harvested lymph nodes. The purpose of this study was to evaluate two laparoscopic techniques to right colectomy, laparoscopic medial to lateral (MtL) approach and laparoscopic lateral to medial (LtM) approach, in patients undergoing a right colectomy for either endoscopically unresectable polyps or carcinoma and determine which technique offers the optimal lymph node harvest. METHODS: Patients that underwent a laparoscopic right colectomy over a 5-year period were identified. Charts were reviewed with regards to demographics, surgical approach, length of stay (LOS) and number of lymph nodes harvested. Variables were statistically analyzed and outcomes compared between the two groups. A p value of less than 0.05 was considered statistically significant. RESULTS: Two hundred thirty-three patients underwent a laparoscopic right colectomy over a 5-year period for endoscopically unresectable polyps or carcinoma. Seventy-nine patients underwent a MtL approach and 154 patients underwent a LtM approach. When comparing the two groups, there were more females in the MtL group relative to the LtM group (78% vs 66%; p = 0.0015). When the outcome of number of lymph nodes harvested was examined, there was a significantly larger number of nodes harvested in the MtL (median = 24) approach compared to the LtM approach (median = 19; p = 0.0002). LOS was similar between the MtL and LtM group (median 4 days for both). CONCLUSIONS: The laparoscopic MtL approach to right colectomy yields a larger lymph node harvest compared to the laparoscopic LtM approach. PMID- 26801788 TI - A Survey of Bariatric Surgical and Reproductive Health Professionals' Knowledge and Provision of Contraception to Reproductive-Aged Bariatric Surgical Patients. AB - BACKGROUND: Over 80 % of bariatric surgical patients are women with obesity in their reproductive years. Obesity adversely affects fertility; the rapid weight loss following bariatric surgery can increase fecundity. Current guidelines recommend avoiding pregnancy for up to 24 months following surgery, but little is known about current contraceptive care of women who undergo bariatric surgery. Two surveys were undertaken with bariatric surgical and contraceptive practitioners in England to establish current contraceptive practices in both groups. METHODS: Two anonymous on-line surveys were sent to all 382 members of the British Obesity and Metabolic Surgery Society (BOMSS) and an estimated 300 contraceptive practitioners in the North East of England. RESULTS: The BOMSS survey elicited a response rate of 17 % (n = 65), mainly from bariatric surgeons (n = 24 (36 %)). Most respondents (97 %) acknowledged the need to educate patients, but contraceptive information was only provided by 7 % (n = 4) of respondents in bariatric surgical clinics. Less than half of respondents were confident discussing contraception, and the majority requested further training, guidance and communication with contraceptive practitioners. The majority of respondents to the contraceptive practitioner survey were general practitioners (28 %, n = 20). Three quarters of respondents reported little knowledge of bariatric surgery, and many reported not seeing women with obesity requiring contraception before (66 %, n = 45) or after surgery (71 %, n = 49). CONCLUSIONS: There is a need to increase knowledge levels of contraception within bariatric surgical teams and to understand why, despite increasing levels of bariatric surgery, women do not seem to be appearing for advice in contraceptive settings. PMID- 26801789 TI - Molecular characterization of the spike and ORF3 genes of porcine epidemic diarrhea virus in the Philippines. AB - Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric pathogen of swine. In the present study, we analyzed the spike genes and ORF3 genes of seven PEDV strains detected in Philippine pigs in June 2014. There are four major epitope regions in the spike glycoprotein: a CO-26K equivalent (COE) domain, SS2 and SS6 epitopes, and an epitope region recognized by the 2C10 monoclonal antibody. Analysis of Philippine strains revealed amino acid substitutions in the SS6 epitope region (LQDGQVKI to SQSGQVKI) of the S1 domain. Substitutions were also detected in the 2C10 epitope region (GPRLQPY to GPRFQPY) in the cytoplasmic domain. Phylogenetic analysis of the complete spike gene sequences from the seven strains revealed that they clustered within the G2 group but were distantly related to the North American and INDELs clusters. Interestingly, these strains were close to Vietnamese PEDVs on the ORF3 genetic tree and showed high (97.0 97.6 %) sequence identity to ORF3 genes at the nucleotide level. PMID- 26801786 TI - Analysis of SSH library of rice variety Aganni reveals candidate gall midge resistance genes. AB - The Asian rice gall midge, Orseolia oryzae, is a serious insect pest causing extensive yield loss. Interaction between the gall midge and rice genotypes is known to be on a gene-for-gene basis. Here, we report molecular basis of HR- (hypersensitive reaction-negative) type of resistance in Aganni (an indica rice variety possessing gall midge resistance gene Gm8) through the construction and analysis of a suppressive subtraction hybridization (SSH) cDNA library. In all, 2,800 positive clones were sequenced and analyzed. The high-quality ESTs were assembled into 448 non-redundant gene sequences. Homology search with the NCBI databases, using BlastX and BlastN, revealed that 73% of the clones showed homology to genes with known function and majority of ESTs belonged to the gene ontology category 'biological process'. Validation of 27 putative candidate gall midge resistance genes through real-time PCR, following gall midge infestation, in contrasting parents and their derived pre-NILs (near isogenic lines) revealed induction of specific genes related to defense and metabolism. Interestingly, four genes, belonging to families of leucine-rich repeat (LRR), heat shock protein (HSP), pathogenesis related protein (PR), and NAC domain-containing protein, implicated in conferring HR+ type of resistance, were found to be up regulated in Aganni. Two of the reactive oxygen intermediates (ROI)-scavenging enzyme-coding genes Cytosolic Ascorbate Peroxidase1, 2 (OsAPx1 and OsAPx2) were found up-regulated in Aganni in incompatible interaction possibly suppressing HR. We suggest that Aganni has a deviant form of inducible, salicylic acid (SA) mediated resistance but without HR. PMID- 26801790 TI - Comparative analysis of drug resistance mutations in the human immunodeficiency virus reverse transcriptase gene in patients who are non-responsive, responsive and naive to antiretroviral therapy. AB - Drug resistance mutations in the Pol gene of human immunodeficiency virus 1 (HIV 1) are one of the critical factors associated with antiretroviral therapy (ART) failure in HIV-1 patients. The issue of resistance to reverse transcriptase inhibitors (RTIs) in HIV infection has not been adequately addressed in the Indian subcontinent. We compared HIV-1 reverse transcriptase (RT) gene sequences to identify mutations present in HIV-1 patients who were ART non-responders, ART responders and drug naive. Genotypic drug resistance testing was performed by sequencing a 655-bp region of the RT gene from 102 HIV-1 patients, consisting of 30 ART-non-responding, 35 ART-responding and 37 drug-naive patients. The Stanford HIV Resistance Database (HIVDBv 6.2), IAS-USA mutation list, ANRS_09/2012 algorithm, and Rega v8.02 algorithm were used to interpret the pattern of drug resistance. The majority of the sequences (96 %) belonged to subtype C, and a few of them (3.9 %) to subtype A1. The frequency of drug resistance mutations observed in ART-non-responding, ART-responding and drug-naive patients was 40.1 %, 10.7 % and 20.58 %, respectively. It was observed that in non-responders, multiple mutations were present in the same patient, while in responders, a single mutation was found. Some of the drug-naive patients had more than one mutation. Thymidine analogue mutations (TAMs), however, were found in non responders and naive patients but not in responders. Although drug resistance mutations were widely distributed among ART non-responders, the presence of resistance mutations in the viruses of drug-naive patients poses a big concern in the absence of a genotyping resistance test. PMID- 26801791 TI - Characteristics and outcome of patients with primary CNS lymphoma in a "real life" setting compared to a clinical trial. AB - We aimed to compare the characteristics and outcome of patients treated within the multi-centre German Primary CNS Lymphoma Study Group 1 trial (G-PCNSL-SG-1; TRIAL group) and patients treated outside this clinical trial ("real-life" setting, R-LIFE group). Therefore, we conducted a retrospective single-centre study in order to analyse all patients with newly diagnosed primary CNS lymphoma (PCNSL) treated consecutively in our institution between November 2000 and June 2015. Altogether, 86 patients were analysed (median 68 years). Twenty patients were treated within (TRIAL) and 66 patients outside the clinical trial (R-LIFE), respectively. The majority (n = 75; 87 %) received high-dose methotrexate as the first-line treatment. Thirty-eight of 66 patients (57.6 %) responded to the first line therapy. The R-LIFE patients were older (median age 70 vs. 62 years; p = 0.005) and had more frequently a worse performance status (ECOG score 2-4: 59.1 vs. 20.0 %; p = 0.004; median Karnofsky index 70 vs. 80 %; p = 0.003) and less frequently a low prognostic score (IELSG score 0-1: 19.7 vs. 45.0 %; p = 0.038), than the TRIAL patients. Median overall survial (OS) was shorter for the R-LIFE patients (9.3 months [95 % CI 1.9-16.7] vs. 33.4 months [95 % CI 17.6-49.2]; p = 0.065). Median progression-free survival (PFS) was significantly inferior for the R-LIFE patients (3.4 months [95 % CI 2.4-4.4] vs. 24.8 months [95 % CI 4.6-45.0]; p = 0.037). Our data indicate that the outcome of PCNSL patients treated outside, but about analogous to the G-PCNSL-SG-1 trial, was poor. This is likely explained by more unfavourable prognostic factors in patients being treated off trial. PMID- 26801792 TI - Infusional dose-adjusted epoch plus bortezomib for the treatment of plasmablastic lymphoma. PMID- 26801795 TI - On the Model-Based Bootstrap With Missing Data: Obtaining a P-Value for a Test of Exact Fit. AB - Evaluating the fit of a structural equation model via bootstrap requires a transformation of the data so that the null hypothesis holds exactly in the sample. For complete data, such a transformation was proposed by Beran and Srivastava (1985) for general covariance structure models and applied to structural equation modeling by Bollen and Stine (1992) . An extension of this transformation to missing data was presented by Enders (2002) , but it is an approximate and not an exact solution, with the degree of approximation unknown. In this article, we provide several approaches to obtaining an exact solution. First, an explicit solution for the special case when the sample covariance matrix within each missing data pattern is invertible is given. Second, 2 iterative algorithms are described for obtaining an exact solution in the general case. We evaluate the rejection rates of the bootstrapped likelihood ratio statistic obtained via the new procedures in a Monte Carlo study. Our main finding is that model-based bootstrap with incomplete data performs quite well across a variety of distributional conditions, missing data mechanisms, and proportions of missing data. We illustrate our new procedures using empirical data on 26 cognitive ability measures in junior high students, published in Holzinger and Swineford (1939) . PMID- 26801794 TI - Prosthetic surgery versus native tissue repair of cystocele: literature review. AB - Cystocele is the most common pelvic organ prolapse. It is defined as the descent of the bladder into the anterior vaginal wall. Aging is significantly associated with the prevalence and severity of pelvic organ prolapse. Treatment may be conservative or surgical according to symptoms, prolapse degree and not forgetting both patient and doctor preferences. Identify the most efficient surgical treatment to treat cystocele and its recurrences. Scientific literature was reviewed searching PubMed/MEDLINE database for articles published between 1996 and 2015 and using the terms pelvic organ prolapse, cystocele, mesh surgery, traditional repair, pelvic organ prolapse recurrence, complications, sexual function. There are two different surgical approaches for the treatment of cystocele: traditional repair and mesh repair. Prosthetic treatment gives higher anatomical success rate and fewer recurrence while traditional anterior repair has less complications. Surgical treatment in general improves both the anatomical success rate and the quality of life. The choice of surgery, between traditional and mesh repair, has to be personalized related to the prolapse grade and women tissues. PMID- 26801796 TI - Doubly-Latent Models of School Contextual Effects: Integrating Multilevel and Structural Equation Approaches to Control Measurement and Sampling Error. AB - This article is a methodological-substantive synergy. Methodologically, we demonstrate latent-variable contextual models that integrate structural equation models (with multiple indicators) and multilevel models. These models simultaneously control for and unconfound measurement error due to sampling of items at the individual (L1) and group (L2) levels and sampling error due the sampling of persons in the aggregation of L1 characteristics to form L2 constructs. We consider a set of models that are latent or manifest in relation to sampling items (measurement error) and sampling of persons (sampling error) and discuss when different models might be most useful. We demonstrate the flexibility of these 4 core models by extending them to include random slopes, latent (single-level or cross-level) interactions, and latent quadratic effects. Substantively we use these models to test the big-fish-little-pond effect (BFLPE), showing that individual student levels of academic self-concept (L1-ASC) are positively associated with individual level achievement (L1-ACH) and negatively associated with school-average achievement (L2-ACH)-a finding with important policy implications for the way schools are structured. Extending tests of the BFLPE in new directions, we show that the nonlinear effects of the L1-ACH (a latent quadratic effect) and the interaction between gender and L1-ACH (an L1 * L1 latent interaction) are not significant. Although random-slope models show no significant school-to-school variation in relations between L1-ACH and L1-ASC, the negative effects of L2-ACH (the BFLPE) do vary somewhat with individual L1 ACH. We conclude with implications for diverse applications of the set of latent contextual models, including recommendations about their implementation, effect size estimates (and confidence intervals) appropriate to multilevel models, and directions for further research in contextual effect analysis. PMID- 26801793 TI - Risk factors for infection after endoscopic ultrasonography-guided drainage of specific types of pancreatic and peripancreatic fluid collections (with video). AB - BACKGROUND: Endoscopic ultrasonography (EUS)-guided drainage is widely used for the treatment of specific types of peripancreatic fluid collections (PFCs). Infectious complications have been reported. It is recommended that the infection rate should be assessed by measuring risk factors. The objectives of this study were to measure whether the risk of infection after EUS-guided drainage was associated with patient- and procedure-related factors. METHODS: Eighty-three patients were eligible for inclusion from September 2008 to November 2012. EUS guided drainage was performed in all patients. Infectious complications were observed, and data on patient- and procedure-related factors were collected. Patient-related factors mainly included age, sex, etiology of PFC, and cyst location and diameter. Procedure-related factors mainly included approach of EUS guided drainage and stent diameter. Separate multivariate logistic regression models for all EUS-guided drainage were carried out. RESULTS: Complete EUS-guided drainage was achieved in all patients. A definitive diagnosis of infection after EUS-guided drainage was made in seven patients. All seven patients had a history of acute pancreatitis, and the cyst diameters were all >15 cm. Three patients had diabetes mellitus. CONCLUSIONS: The cyst diameter was an independent risk factor for infection. Larger cysts with a diameter >15 cm should perhaps be drained initially with multiple pigtail or a larger diameter self-expandable metal stents to try to avoid infection. PMID- 26801797 TI - Normal Versus Noncentral Chi-square Asymptotics of Misspecified Models. AB - The noncentral chi-square approximation of the distribution of the likelihood ratio (LR) test statistic is a critical part of the methodology in structural equation modeling. Recently, it was argued by some authors that in certain situations normal distributions may give a better approximation of the distribution of the LR test statistic. The main goal of this article is to evaluate the validity of employing these distributions in practice. Monte Carlo simulation results indicate that the noncentral chi-square distribution describes behavior of the LR test statistic well under small, moderate, and even severe misspecifications regardless of the sample size (as long as it is sufficiently large), whereas the normal distribution, with a bias correction, gives a slightly better approximation for extremely severe misspecifications. However, neither the noncentral chi-square distribution nor the theoretical normal distributions give a reasonable approximation of the LR test statistics under extremely severe misspecifications. Of course, extremely misspecified models are not of much practical interest. We also use the Thurstone data ( Thurstone & Thurstone, 1941 ) from a classic study of mental ability for our illustration. PMID- 26801799 TI - Special MBR Section: SMEP Student Paper Competition Abstracts. PMID- 26801798 TI - How Bias Reduction Is Affected by Covariate Choice, Unreliability, and Mode of Data Analysis: Results From Two Types of Within-Study Comparisons. AB - This study uses within-study comparisons to assess the relative importance of covariate choice, unreliability in the measurement of these covariates, and whether regression or various forms of propensity score analysis are used to analyze the outcome data. Two of the within-study comparisons are of the four-arm type, and many more are of the three-arm type. To examine unreliability, simulations of differences in reliability are deliberately introduced into the 2 four-arm studies. Results are similar across the samples of studies reviewed with their wide range of non-experimental designs and topic areas. Covariate choice counts most, unreliability next most, and the mode of data analysis hardly matters at all. Unreliability has larger effects the more important a covariate is for bias reduction, but even so the very best covariates measured with a reliability of only .60 still do better than substantively poor covariates that are measured perfectly. Why regression methods do as well as propensity score methods used in several different ways is a mystery still because, in theory, propensity scores would seem to have a distinct advantage in many practical applications, especially those where functional forms are in doubt. PMID- 26801800 TI - Abstract: Towards Automatic Coding of Facial Expression. PMID- 26801801 TI - Abstract: Estimating Latent Variable Interactions with Binary and Ordinal Data. PMID- 26801802 TI - Abstract: Lag as Moderator Models for Longitudinal Data. PMID- 26801803 TI - Abstract: Propensity Score Matching in a Meta-Analysis Comparing Randomized and Non-Randomized Studies. PMID- 26801804 TI - Abstract: A General Method to Derive Covariances between Parameter Estimates in Mediation Models. PMID- 26801805 TI - Abstract: Treatment Effects in Randomized Longitudinal Experiments with Different Types of Non-Ignorable Dropout. PMID- 26801807 TI - Erratum to "An Extension of Dominance Analysis to Canonical Correlation Analysis". PMID- 26801806 TI - Abstract: A Biometric Latent Curve Analysis of Visual Memory Development Using Data from the Colorado Adoption Project. PMID- 26801808 TI - Ectopic Hydrocele After Testicular Transposition. AB - A 55-year-old man was treated for Fournier gangrene in 2004 with radical debridement and bilateral testicular transposition to the medial thighs. Eight years later, bilateral hydroceles formed. After conservative measures failed for treatment of the hydroceles, the condition was treated during desired testicular relocation, and creation of a neoscrotum. In the case presented, bilateral thigh hydroceles may have developed from lymphatic injury during testicular transposition. To our knowledge, this is the first case report of bilateral hydrocele testis in the medial thigh pouches following ectopic testicular transposition. PMID- 26801809 TI - Defining the Pathways of Parental Decision-making and Satisfaction Levels About Newborn Circumcision in a Setting Where Traditional Male Circumcision is Prevalent: An Online Survey Study. AB - OBJECTIVE: To investigate the decision-making attitudes, course of informed consent, and satisfaction levels of parents who opted for newborn circumcision (NC) in a societal setting where the timing of circumcision is generally determined by tradition. METHODS: Online questionnaire was sent to 1235 parents of boys who had NC. RESULTS: The response rate was 50.4%. The final decision of newborn circumcision depended on the mother in 51.47%. Nearly 75% of circumcisions were performed before hospital discharge. The most common (70.65%) reported reason for parents' choice was medical/hygienic. When evaluating their decision, 93.05% refused any feelings of regret and 96.26% stated they would decide the same if they had another son. The source of information on newborn circumcision was mostly physicians (39.27%), followed by friends and family (31.2%). Parental preference, having nonreligious motives, and being previously informed about the procedure by experienced peers appeared as significant factors on the decision regarding timing of NC. In total, 79.90% ranked their satisfaction level as "very satisfied" on a Likert scale. The mean rate of satisfaction was significantly higher in parents who acquired previous information from healthcare providers and who acknowledged sufficient preprocedural counseling before giving consent. CONCLUSION: In a society where the timing of circumcision is usually determined by faiths and traditions, parental decision-making on newborn circumcision is greatly influenced by personal choices of parents, based on timely, accurate, and adequate information received from peers and healthcare providers. Medical providers play an important role on the informed decision of parents and impact on satisfaction with prior decision and outcomes of newborn circumcision. PMID- 26801810 TI - Long-term Outcomes of Robot-assisted Laparoscopic Pyeloplasty for Ureteropelvic Junction Obstruction. AB - OBJECTIVE: To describe the long-term outcomes of robot-assisted laparoscopic pyeloplasty (RALP) for the correction of ureteropelvic junction (UPJ) obstruction. METHODS: A retrospective electronic medical record review of RALPs from October 2002 to July 2014 was performed, with additional follow-up for patients released from regular urological care obtained by phone. RALP success was defined as resolution of symptoms of UPJ obstruction, improved hydronephrosis radiographically, or resolution of obstruction on follow-up Tc-99m mercaptoacetyltriglycine renal scan, intravenous pyelogram, or Whitaker test. RALP failure was defined as persistence of symptoms with obstruction demonstrated on functional imaging or requirement for a subsequent UPJ procedure. RESULTS: A total of 129 cases were identified, with an average patient age of 34.3 years. Stented RALP was performed in 80.6% of cases whereas 19.4% of patients underwent stentless RALP. A dismembered technique was performed in 90.7% of pyeloplasties, whereas 9.3% were nondismembered Fenger, Y-V, or flap pyeloplasties. Five intraoperative complications and 18 postoperative complications (Clavien I-IIIb) were described. One hundred twenty-nine patients received follow-up for a mean of 33.8 months (range 1-147 months). RALP was successful in 125/129 (96.9%), with an 8-year failure-free survival of 91.5%. When considering only stented pyeloplasties, the 8-year failure-free survival was 96.3%. CONCLUSION: RALP is a safe and effective minimally invasive method for correction of UPJ obstruction, resulting in lasting improvement in symptoms and resolution of obstruction for most patients. PMID- 26801811 TI - Electrochemical Potential Derived from Atomic Cluster Structures. AB - Based on the atomic cluster structures and free electron approximation model, it is revealed that the electrochemical potential (ECP) for the system of interest is proportional to the reciprocal of atomic cluster radius squared, i.e., phi = k.(1/r(2)). Applied to elemental crystals, the correlation between atomic cluster radii and the ECP that we have predicted agrees well with the previously reported results. In addition, some other physicochemical properties associated with the ECP have also been found relevant to the atomic cluster radii of materials. Thus, the atomic cluster radii can be perceived as an effective characteristic parameter to measure the ECP and related properties of materials. Our results provide a better understanding of ECP directly from the atomic structures perspective. PMID- 26801813 TI - N-of-1 randomised controlled trials in health psychology and behavioural medicine: A commentary on Nyman et al., 2016. PMID- 26801812 TI - Insights into epigenetic landscape of recombination-free regions. AB - Genome architecture is shaped by gene-rich and repeat-rich regions also known as euchromatin and heterochromatin, respectively. Under normal conditions, the repeat-containing regions undergo little or no meiotic crossover (CO) recombination. COs within repeats are risky for the genome integrity. Indeed, they can promote non-allelic homologous recombination (NAHR) resulting in deleterious genomic rearrangements associated with diseases in humans. The assembly of heterochromatin is driven by the combinatorial action of many factors including histones, their modifications, and DNA methylation. In this review, we discuss current knowledge dealing with the epigenetic signatures of the major repeat regions where COs are suppressed. Then we describe mutants for epiregulators of heterochromatin in different organisms to find out how chromatin structure influences the CO rate and distribution. PMID- 26801815 TI - Metronomic therapy can increase quality of life during paediatric palliative cancer care, but careful patient selection is essential. AB - AIM: Children with refractory or high-risk malignancies frequently suffer from poor quality of life during palliative care. This study explored the effect of metronomic drug administration on survival and quality of life in paediatric patients with various refractory or high-risk tumours. METHODS: We treated 17 patients with a maintenance therapy that consisted of metronomic thalidomide, etoposide and celecoxib. The endpoints of the study were overall and progression free survival, changes in the Karnofsky-Lansky scores from baseline to the end of the study therapy and radiological responses. RESULTS: The median overall survival after the start of the study therapy was 6.2 months (range 2.0-57.7), and the six-, 12- and 24-month survival rates were 59%, 18% and 18%, respectively. The median progression-free survival was 3.2 months (range 0.3 17.8). The Karnofsky-Lansky scores increased significantly during the study therapy (p = 0.02), with 35% of the patients having a transient improvement in their clinical status. Radiologically, one partial response and two disease stabilisations were encountered. Grade III-V adverse events occurred in 76% of the patients. CONCLUSION: Metronomic therapy may increase the quality of life during palliative care for childhood cancer, but requires careful patient selection to minimise the risk of serious adverse events. PMID- 26801816 TI - Decellularized Liver Extracellular Matrix as Promising Tools for Transplantable Bioengineered Liver Promotes Hepatic Lineage Commitments of Induced Pluripotent Stem Cells. AB - Liver transplantation is the last resort for liver failure patients. However, due to the shortage of donor organs, bioengineered liver generated from decellularized whole liver scaffolds and induced pluripotent stem cell (iPSC) derived hepatocytes (iPSC-Heps) is being studied as an alternative approach to treat liver disease. Nevertheless, there has been no report on both the interaction of iPSC-Heps with a liver extracellular matrix (ECM) and the analysis of recellularized iPSC-Heps into the whole liver scaffolds. In this study, we produced porcine iPSC-Heps, which strongly expressed the hepatic markers alpha fetoprotein and albumin and exhibited hepatic functionalities, including glycogen storage, lipid accumulation, low-density lipoprotein uptake, and indocyanine green metabolism. Supplementation of ECM from porcine decellularized liver containing liver-derived growth factors stimulated the albumin expression of porcine iPSC-Heps during differentiation procedures. The iPSC-Heps were reseeded into decellularized liver scaffolds, and the recellularized liver was cultured using a continuous perfusion system. The recellularized liver scaffolds were transplanted into rats for a short term, and the grafts expressed hepatocyte markers and did not rupture. These results provide a foundation for development of bioengineered liver using stem cell and decellularized scaffolds. PMID- 26801817 TI - Enhanced Delivery of Plasmid Encoding Interleukin-12 Gene by Diethylene Triamine Penta-Acetic Acid (DTPA)-Conjugated PEI Nanoparticles. AB - Recombinant therapeutic proteins have been considered as an efficient category of medications used for the treatment of various diseases. Despite their effectiveness, there are some reports on the systemic adverse effects of recombinant therapeutic proteins limiting their wide clinical applications. Among different cytokines used for cancer immunotherapy, interleukin-12 (IL-12) has shown great ability as a powerful antitumor and antiangiogenic agent. However, significant toxic reactions following the systemic administration of IL-12 have led researchers to seek for alternative approaches such as the delivery and local expression of the IL-12 gene inside the tumor tissues. In order to transfer the plasmid encoding IL-12 gene, the most extensively investigated polycationic polymer, polyethylenimine (PEI), was modified by diethylene triamine penta-acetic acid (DTPA) to modulate the hydrophobic-hydrophilic balance of the polymer as well as its toxicity. DTPA-conjugated PEI derivatives were able to form complexes in the size range around 100-180 nm with great condensation ability and protection of the plasmid against enzymatic degradation. The highest gene transfer ability was achieved by the DTPA-conjugated PEI at the conjugation degree of 0.1 % where the level of IL-12 production increased up to twofold compared with that of the unmodified PEI. Results of the present study demonstrated that modulation of the surface positive charge of PEI along with the improvement of the polymer hydrophobic balance could be considered as a successful strategy to develop safe and powerful nanocarriers. PMID- 26801818 TI - Signal Amplification in Field Effect-Based Sandwich Enzyme-Linked Immunosensing by Tuned Buffer Concentration with Ionic Strength Adjuster. AB - Miniaturization of the sandwich enzyme-based immunosensor has several advantages but could result in lower signal strength due to lower enzyme loading. Hence, technologies for amplification of the signal are needed. Signal amplification in a field effect-based electrochemical immunosensor utilizing chip-based ELISA is presented in this work. First, the molarities of phosphate buffer saline (PBS) and concentrations of KCl as ionic strength adjuster were optimized to maximize the GOx glucose-based enzymatic reactions in a beaker for signal amplification measured by change in the voltage shift with an EIS device (using 20 MUl of solution) and validated with a commercial pH meter (using 3 ml of solution). The PBS molarity of 100 MUM with 25 mM KCl provided the maximum voltage shift. These optimized buffer conditions were further verified for GOx immobilized on silicon chips, and similar trends with decreased PBS molarity were obtained; however, the voltage shift values obtained on chip reaction were lower as compared to the reactions occurring in the beaker. The decreased voltage shift with immobilized enzyme on chip could be attributed to the increased Km (Michaelis-Menten constant) values in the immobilized GOx. Finally, a more than sixfold signal enhancement (from 8 to 47 mV) for the chip-based sandwich immunoassay was obtained by altering the PBS molarity from 10 to 100 MUM with 25 mM KCl. PMID- 26801819 TI - Malignant melanoma in a patient with mal de Meleda. PMID- 26801820 TI - The evolution of colour pattern complexity: selection for conspicuousness favours contrasting within-body colour combinations in lizards. AB - Many animals display complex colour patterns that comprise several adjacent, often contrasting colour patches. Combining patches of complementary colours increases the overall conspicuousness of the complex pattern, enhancing signal detection. Therefore, selection for conspicuousness may act not only on the design of single colour patches, but also on their combination. Contrasting long- and short-wavelength colour patches are located on the ventral and lateral surfaces of many lacertid lizards. As the combination of long- and short wavelength-based colours generates local chromatic contrast, we hypothesized that selection may favour the co-occurrence of lateral and ventral contrasting patches, resulting in complex colour patterns that maximize the overall conspicuousness of the signal. To test this hypothesis, we performed a comparative phylogenetic study using a categorical colour classification based on spectral data and descriptive information on lacertid coloration collected from the literature. Our results demonstrate that conspicuous ventral (long-wavelength based) and lateral (short-wavelength-based) colour patches co-occur throughout the lacertid phylogeny more often than expected by chance, especially in the subfamily Lacertini. These results suggest that selection promotes the evolution of the complex pattern rather than the acquisition of a single conspicuous colour patch, possibly due to the increased conspicuousness caused by the combination of colours with contrasting spectral properties. PMID- 26801821 TI - Effect of intravenous iron on outcomes of acute kidney injury. AB - BACKGROUND: Little is known about benefit versus risk in treating iron deficiency anemia with intravenous (IV) iron in patients with acute kidney injury (AKI). Concerns about adverse outcomes may dissuade use and could contribute to greater use of red blood cell (RBC) transfusion. STUDY DESIGN AND METHODS: We performed a retrospective case-control study of patients with AKI who received IV iron (cases) compared to those with AKI without IV iron (controls). RESULTS: We identified 67 cases and 67 controls matched for age, stage of chronic kidney disease, and severity of anemia (hemoglobin [Hb], 7.7 +/- 0.1 mg/dL vs. 7.5 +/- 0.1 mg/dL; p = 0.47). Cases tended to be sicker with longer length of stay (27 + 4 days vs. 15 + 1.3 days; p = 0.003) and more intensive care unit days (13 + 2 days vs. 5 + 1 days; p = 0.003), more often with diagnosis of sepsis and greater number of antibiotics used (2.7 +/- 0.3 vs. 1.8 +/- 0.2; p = 0.02). Sepsis and AKI preceded use of IV iron. Despite greater illness severity, there was no difference in dialysis (38.8% vs. 34.3%; p = 0.59), mortality (24% vs. 21%; p = 0.679), or severity and/or recovery of AKI. Discharge Hb was similar (9.0 +/- 0.1 mg/dL vs. 9.1 +/- 0.1 mg/dL; p = 0.47). IV iron was used later in the stay and hence the cases also had more RBC transfusions. CONCLUSIONS: We were unable to find any adverse consequences of use of IV iron when used to treat anemia in patients with AKI in regard to recovery of AKI or mortality even in patients with a diagnosis of sepsis. Consideration of preemptive use of IV iron in AKI with severe anemia is warranted to determine if this would reduce RBC transfusion. PMID- 26801822 TI - Fluctuating and directional asymmetry in the long bones of captive cotton-top tamarins (Saguinus oedipus). AB - OBJECTIVES: Skeletal asymmetries reflect developmental stability and mechanical, functional, and physiological influences on bone growth. In humans, researchers have documented the greatest limb bone bilateral asymmetry in diaphyseal breadths, with less asymmetry in articular and maximum length dimensions. However, it remains unclear as to whether the pattern observed for humans is representative of nonhuman primates, wherein bilateral loading may minimize directional asymmetry. This study adds to the small body of asymmetry data on nonhuman primates by investigating patterns of long bone asymmetry in a skeletal sample of Saguinus oedipus (cotton-top tamarin). MATERIALS AND METHODS: Humeri, radii, ulnae, femora, and tibiae of 76 adult captive cotton-top tamarin skeletons (48 males, 28 females) were measured bilaterally. We included maximum length, midshaft diaphyseal breadths, and at least one articular measurement for each bone to assess directional (DA) and fluctuating asymmetry (FA) in each dimension. RESULTS: Most dimensions exhibit significant FA, and very few have significant DA; DA is limited to the lower limb, especially in knee dimensions. Overall, the magnitudes of asymmetry in tamarins have a consistent ranking that follows the same pattern as found in humans. DISCUSSION: This first study of DA and FA among multiple dimensions throughout the limbs of a non-hominoid primate suggests that previously-reported patterns of human bilateral asymmetry are not exclusive to humans. The results further indicate potential underlying differences in constraints on variation within limb bones. While processes shaping variation await further study, our results argue that different long bone dimensions may reflect dissimilar evolutionary processes. PMID- 26801823 TI - Identification of microRNAs regulating Hlxb9 gene expression during the induction of insulin-producing cells. AB - Bone marrow mesenchymal stem cells (bMSCs) with the capacity of self- renewal and multilineage differentiation are promising sources for cell replacement therapy in diabetes. Here, we developed an effective method with activin A, conophylline, and nicotinamide to induce mouse bMSCs to differentiate into insulin-producing cells (IPCs). The homeobox gene Hlxb9 (encoding HB9) is prominently expressed in adult human pancreas, which can also play a key role during the induction of IPCs. To find the microRNAs (miRNAs) regulating Hlxb9 gene expression, we respectively used miRanda and TargetScan to predict and got the intersection, miR 200a and miR-141, further identified by the Dual-Luciferase assay. The results illustrated miR-200a and miR-141 could inhibit the expression of Hlxb9 by binding to its mRNA 3'UTR. Furthermore, the expression of miR-200a and miR-141 was almost reciprocal to that of Hlxb9. Overexpression of miR-200a and miR-141 downregulated the expression of pancreatic progenitor cell markers Hlxb9 and Pdx1. Therefore, miR-200a and miR-141 may directly or indirectly regulate the expression of pancreatic islet transcription factors to control the differentiation of IPCs. PMID- 26801824 TI - Identification of a novel starfish neuropeptide that acts as a muscle relaxant. AB - Neuropeptides that act as muscle relaxants have been identified in chordates and protostomian invertebrates but little is known about the molecular identity of neuropeptides that act as muscle relaxants in deuterostomian invertebrates (e.g. echinoderms) that are 'evolutionary intermediates' of chordates and protostomes. Here, we have used the apical muscle of the starfish Patiria pectinifera to assay for myorelaxants in extracts of this species. A hexadecapeptide with the amino acid sequence Phe-Gly-Lys-Gly-Gly-Ala-Tyr-Asp-Pro-Leu-Ser-Ala-Gly-Phe-Thr-Asp was identified and designated starfish myorelaxant peptide (SMP). Cloning and sequencing of a cDNA encoding the SMP precursor protein revealed that it comprises 12 copies of SMP as well as 3 peptides (7 copies in total) that are structurally related to SMP. Analysis of the expression of SMP precursor transcripts in P. pectinifera using qPCR revealed the highest expression in the radial nerve cords and lower expression levels in a range of neuromuscular tissues, including the apical muscle, tube feet and cardiac stomach. Consistent with these findings, SMP also caused relaxation of tube foot and cardiac stomach preparations. Furthermore, SMP caused relaxation of apical muscle preparations from another starfish species - Asterias amurensis. Collectively, these data indicate that SMP has a general physiological role as a muscle relaxant in starfish. Interestingly, comparison of the sequence of the SMP precursor with known neuropeptide precursors revealed that SMP belongs to a bilaterian family of neuropeptides that include molluscan pedal peptides (PP) and arthropodan orcokinins (OK). This is the first study to determine the function of a PP/OK type peptide in a deuterostome. Pedal peptide/orcokinin (PP/OK)-type peptides are a family of structurally related neuropeptides that were first identified and functionally characterised in protostomian invertebrates. Here, we report the discovery of starfish myorelaxant peptide (SMP), a novel member of the PP/OK-type neuropeptide identified in the starfish Patiria pectinifera (phylum Echinodermata). SMP is the first PP/OK-type neuropeptide to be functionally characterised in a deuterostome. PMID- 26801825 TI - Resveratrol exerts antidepressant properties in the chronic unpredictable mild stress model through the regulation of oxidative stress and mTOR pathway in the rat hippocampus and prefrontal cortex. AB - Depression is one of the most common neuropsychiatric disorders and has been associated with oxidative stress and brain protein alterations. Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities including potent antidepressant-like effects. The present study attempts to explore the mechanisms underlying the antidepressant-like action of resveratrol by measuring oxidative stress parameters and phosphorylation of AKT/mTOR pathway in the rat hippocampus and prefrontal cortex (PFC) exposed to the chronic unpredictable mild stress (CUMS). Male Wistar rats were subjected to CUMS protocol for a period of 4 weeks to induce depressive-like behavior. The results showed that resveratrol treatment (80 mg/kg/i.p. 4 weeks) significantly reversed the CUMS-induced behavioral abnormalities (reduced sucrose preference, increased immobility time and decreased locomotor activity) and biochemical changes (increased lipid peroxidation and decreased superoxide dismutase). Additionally, CUMS exposure significantly decreased phosphorylation of Akt and mTOR in the hippocampus and PFC, while resveratrol treatment normalized these parameters. In conclusion, our study showed that resveratrol exerted antidepressant-like effects in CUMS rats, which was mediated in part by its antioxidant action, up-regulation of phosphor-Akt and mTOR levels in the hippocampus and PFC. PMID- 26801826 TI - Effect of behavioral testing on spine density of basal dendrites in the CA1 region of the hippocampus modulated by (56)Fe irradiation. AB - A unique feature of the space radiation environment is the presence of high energy charged particles, including (56)Fe ions, which can present a significant hazard to space flight crews during and following a mission. (56)Fe irradiation induced cognitive changes often involve alterations in hippocampal function. These alterations might involve changes in spine morphology and density. In addition to irradiation, performing a cognitive task can also affect spine morphology. Therefore, it is often hard to determine whether changes in spine morphology and density are due to an environmental challenge or group differences in performance on cognitive tests. In this study, we tested the hypothesis that the ability of exploratory behavior to increase specific measures of hippocampal spine morphology and density is affected by (56)Fe irradiation. In sham irradiated mice, exploratory behavior increased basal spine density in the CA1 region of the hippocampus and the enclosed blade of the dentate gyrus. These effects were not seen in irradiated mice. In addition, following exploratory behavior, there was a trend toward a decrease in the percent stubby spines on apical dendrites in the CA3 region of the hippocampus in (56)Fe-irradiated, but not sham-irradiated, mice. Other hippocampal regions and spine measures affected by (56)Fe irradiation showed comparable radiation effects in behaviorally naive and cognitively tested mice. Thus, the ability of exploratory behavior to alter spine density and morphology in specific hippocampal regions is affected by (56)Fe irradiation. PMID- 26801827 TI - Modulatory effects of dopamine receptors on associative learning performance in zebrafish (Danio rerio). AB - The zebrafish (Danio rerio) has been shown to be an insatiable rival for mammalian model organisms, in many research areas including behavioral neuroscience. Despite a growing body of evidence on successful performance of zebrafish in learning paradigms, little progress has been made toward elucidating the role of neuromodulatory systems in regulation of cognitive functions in this species. Here, we investigated the modulatory effect of dopamine, one of the major neurotransmitters of importance in the brain, on cognitive performance of zebrafish. To this end, a plus maze associative learning paradigm was employed where fish trained to associate a conditioned visual stimulus with the sight of conspecifics as the rewarding unconditioned stimulus. Experimental fish were exposed to dopaminergic agonists (SKF-38393 and quinpirole) and antagonists (SCH 23390 and eticlopride) immediately before training, after training, and just before probe. Pre- and post-training administration of SKF-38393 and SCH-23390 enhanced learning and memory performance of zebrafish in the maze but not when given immediately before the probe trial. Quinpirole also enhanced probe trial performance when administered immediately before training and before the probe but not when given after training. Furthermore, fish that received eticlopride before training, after training or before the probe showed impairment in associative learning performance. Taken together, our results shed first light on modulatory role of dopamine receptors in different aspects of learning and memory in zebrafish. PMID- 26801828 TI - Antidepressant-like effect of cannabidiol injection into the ventral medial prefrontal cortex-Possible involvement of 5-HT1A and CB1 receptors. AB - RATIONALE: Systemic administration of cannabidiol (CBD), the main non psychotomimetic constituent of Cannabis sativa, induces antidepressant-like effects. The mechanism of action of CBD is thought to involve the activation of 5 HT1A receptors and the modulation of endocannabinoid levels with subsequent CB1 activation. The brain regions involved in CBD-induced antidepressant-like effects remain unknown. The ventral medial prefrontal cortex (vmPFC), which includes the infralimbic (IL) and prelimbic (PL) subregions, receives dense serotonergic innervation and plays a significant role in stress responses. OBJECTIVE: To test the hypothesis that the administration of CBD into the IL or PL would induce an antidepressant-like effect through 5-HT1A and CB1 activation. METHODS: Rats received intra-IL or -PL microinjections of CBD (10-60 nmol/side), 8-OH-DPAT (5 HT1A agonist, 5-10 nmol/side), anandamide (AEA, 0.5 pmol/side) or vehicle (0.2 MUl/side) and were submitted to the forced swimming (FST) or to the open field (OFT) tests. Independent CBD-treated groups were pre-treated with WAY100635 (10, 30 nmol/side, 5-HT1A antagonist) or AM251 (10 pmol/side, CB1 antagonist) and submitted to the same tests. An additional group was treated with WAY100635 followed by anandamide. RESULTS: CBD (PL: 10-60 nmol; IL:45-60 nmol) and 8-OH DPAT (10 nmol) administration significantly reduced the immobility time in the FST, without changing locomotor activity in the OFT. WAY100635 (30 nmol) did not induce effect per se but blocked CBD, 8-OH-DPAT and AEA effects. Additionally, AM251 blocked CBD-effects. CONCLUSION: administration of CBD into the vmPFC induces antidepressant-like effects possibly through indirect activation of CB1 and 5-HT1A receptors. PMID- 26801829 TI - The role of adult neurogenesis in psychiatric and cognitive disorders. AB - Neurogenesis in mammals occurs throughout life in two brain regions: the ventricular-subventricular zone (V-SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus. Development and regulation of the V-SVZ and SGZ is unique to each brain region, but with several similar characteristics. Alterations to the production of new neurons in neurogenic regions have been linked to psychiatric and neurodegenerative disorders. Decline in neurogenesis in the SGZ correlates with affective and psychiatric disorders, and can be reversed by antidepressant and antipsychotic drugs. Likewise, neurogenesis in the V-SVZ can also be enhanced by antidepressant drugs. The regulation of neurogenesis by neurotransmitters, particularly monoamines, in both regions suggests that aberrant neurotransmitter signaling observed in psychiatric disease may play a role in the pathology of these mental health disorders. Similarly, the cognitive deficits that accompany neurodegenerative disease may also be exacerbated by decreased neurogenesis. This review explores the regulation and function of neural stem cells in rodents and humans, and the involvement of factors that contribute to psychiatric and cognitive deficits. This article is part of a Special Issue entitled SI:StemsCellsinPsychiatry. PMID- 26801830 TI - Phonological code retrieval during picture naming: Influence of consonant class. AB - Investigations of the time course of various stages of lexical processing have indicated either early or late onset of brain activation for phonological code retrieval. The basis of the differential findings is unclear, but factors related to segmental phonology appear to be part of it. The purpose of the present study was to determine whether phonological encoding is influenced by consonant type. Undergraduate students were presented pictures of common and familiar objects to name. Each picture label had an initial liquid (/l/, /r/) or a stop (/b/, /d/) consonant. Accuracy of picture naming was high and comparable for the two stimulus sets. However, words beginning with liquids elicited larger N2 ERP responses than did those with initial stops. Cluster permutation analysis indicated that the ERP responses elicited by words in the two stimulus sets differed between 293 ms and 371 ms post picture onset. These findings point to a late onset of phonological code retrieval. They have implications for segmental phonology and/or motor planning and execution of speech. PMID- 26801831 TI - Pharmacotherapy in rehabilitation of post-acute traumatic brain injury. AB - There are nearly 1.8 million annual emergency room visits and over 289,000 annual hospitalizations related to traumatic brain injury (TBI). The goal of this review article is to highlight pharmacotherapies that we often use in the clinic that have been shown to benefit various sequelae of TBI. We have decided to focus on sequelae that we commonly encounter in our practice in the post-acute phase after a TBI. These symptoms are hyper-arousal, agitation, hypo-arousal, inattention, slow processing speed, memory impairment, sleep disturbance, depression, headaches, spasticity, and paroxysmal sympathetic hyperactivity. In this review article, the current literature for the pharmacological management of these symptoms are mentioned, including medications that have not had success and some ongoing trials. It is clear that the pharmacological management specific to those with TBI is often based on small studies and that often treatment is based on assumptions of how similar conditions are managed when not relating to TBI. As the body of the literature expands and targeted treatments start to emerge for TBI, the function of pharmacological management will need to be further defined. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID- 26801832 TI - Design of biocompatible immobilized Candida rugosa lipase with potential application in food industry. AB - BACKGROUND: Biocatalysts are a promising alternative for the production of natural flavor compounds. Candida rugosa lipase (CRL) is a particularly important biocatalyst owing to its remarkable efficiency in both hydrolysis and synthesis. However, additional stabilization is necessary for successful industrial implementation. This study presents an easy and time-saving method for immobilizing this valuable enzyme on hydroxyapatite (HAP), a biomaterial with high protein-binding capacity. RESULTS: Targeted immobilized CRL was obtained in high yield of >=98%. Significant lipase stabilization was observed upon immobilization: at 60 degrees C, immobilized lipase (HAP-CRL) retained almost unchanged activity after 3 h, while free CRL lost 50% of its initial activity after only 30 min. The same trend was observed with tested organic solvents. Methanol and hexane had the most pronounced effect: after 3 h, only HAP-CRL was stable and active, while CRL was completely inactivated. The practical value of the prepared catalyst was tested in the synthesis of the aroma ester methyl acetate in hexane. Reaction yields were 2.6 and 52.5% for CRL and HAP-CRL respectively. CONCLUSION: This research has successfully combined an industrially prominent biocatalyst, CRL, and a biocompatible, environmentally suitable carrier, HAP, into an immobilized preparation with improved catalytic properties. The obtained CRL preparation has excellent potential for the food and flavor industries, major consumers in the global enzyme market. (c) 2016 Society of Chemical Industry. PMID- 26801833 TI - C55 bacteriocin produced by ETB-plasmid positive Staphylococcus aureus strains is a key factor for competition with S. aureus strains. AB - Exfoliative toxin (ET) produced by Staphylococcus aureus is closely associated with the onset of bullous impetigo. To date, three ETs (ETA, ETB and ETD) have been identified. The gene encoding ETB is located in a plasmid designated pETB. Bacteriocin synthesis genes are also located in this plasmid and pETB-positive strains reportedly produce the C55 bacteriocin. In this study, the antibacterial activity against S. aureus strains of the bacteriocin produced by the pETB positive strain TY4 was investigated. This bacteriocin demonstrated antibacterial activity against all pETB-negative but not pETB-positive strains, including TY4. Additionally, a TY4- strain from which the pETB plasmid had been deleted exhibited susceptibility to the bacteriocin. Further experiments revealed that two immunity factors (orf 46-47 and orf 48) downstream of the bacteriocin synthesis genes in the pETB plasmid are associated with immunity against the bacteriocin produced by TY4. The TY4- with orf46-47 strain exhibited complete resistance to bacteriocin, whereas the TY4- with orf48 strain exhibited partial resistance. Whether bacteriocin affects the proportion of each strain when co cultured with S. aureus strains was also investigated. When TY4 or TY4- was co cultured with 209P strain, which is susceptible to the bacteriocin, the proportion of 209P co-cultured with TY4 was significantly less than when 209P was co-cultured with TY4-, whereas the proportion of TY4- with orf46-48 co-cultured with TY4 was greater than with TY4-. These results suggest that the C55 bacteriocin produced by pETB-positive strains affects the proportion of each strain when pETB-positive and -negative strains co-exist. PMID- 26801834 TI - Three-dimensional printing of orbital and peri-orbital masses in three dogs and its potential applications in veterinary ophthalmology. AB - OBJECTIVE: To describe the technique and utility of three-dimensional (3D) printing for orbital and peri-orbital masses and discuss other potential applications for 3D printing. ANIMALS STUDIED: Three dogs with a chronic history of nonpainful exophthalmos. PROCEDURES: Computed tomography (CT) and subsequent 3D printing of the head was performed on each case. CT confirmed a confined mass, and an ultrasound-guided biopsy was obtained in each circumstance. An orbitotomy was tentatively planned for each case, and a 3D print of each head with the associated globe and mass was created to assist in surgical planning. RESULTS: In case 1, the mass was located in the cranioventral aspect of the right orbit, and the histopathologic diagnosis was adenoma. In case 2, the mass was located within the lateral masseter muscle, ventral to the right orbit between the zygomatic arch and the ramus of the mandible. The histopathologic diagnosis in case 2 was consistent with a lipoma. In case 3, the mass was located in the ventral orbit, and the histopathologic diagnosis was histiocytic cellular infiltrate. CONCLUSIONS: Three-dimensional printing in cases with orbital and peri-orbital masses has exceptional potential for improved surgical planning and provides another modality for visualization to help veterinarians, students, and owners understand distribution of disease. Additionally, as the techniques of 3D printing continue to evolve, the potential exists to revolutionize ocular surgery and drug delivery. PMID- 26801835 TI - In Memoriam Larry L. Hench, Ph.D. 1938 - 2015. PMID- 26801836 TI - Risk Factors and Spatial Distribution of Canine Coccidioidomycosis in California, 2005-2013. AB - Given the predisposition of dogs to coccidioidomycosis, identification of high risk regions for coccidioidomycosis in dogs may improve early recognition of emerging human disease. We sought to identify risk factors for canine coccidioidomycosis and to produce a risk map for coccidioidomycosis occurrence. Forty-one dogs seen at the Veterinary Medical Teaching Hospital at the University of California, Davis, between 2005 and 2013 with coccidioidomycosis were identified together with a control population of 79 dogs. Owners were surveyed about potential risk factors including younger age, digging behaviour, and travel to Arizona or the California central valley. Risk factors were analysed using logistic regression analysis. Outcomes were used to generate a risk map for coccidioidomycosis in California. There was a significant correlation between the reported rate of coccidioidomycosis in humans and our risk map for canine coccidioidomycosis in California, supporting the idea of dogs as sentinels for emerging geographic areas for coccidioidomycosis in humans. PMID- 26801864 TI - Long noncoding RNA H19 inhibits the proliferation of fetal liver cells and the Wnt signaling pathway. AB - In this study, we found that H19 is the most strongly differentially expressed long noncoding RNA (lncRNA) during liver development. H19 may inhibit the proliferation of fetal liver cells by blocking the interaction between heterogeneous nuclear ribonucleoprotein (hnRNP) U and actin, which results in gene transcriptional repression. Based on ChIP-seq analysis, we found that genes involved in the Wnt signaling pathway are enriched among hnRNP U-binding genes. Further investigation demonstrated that hnRNP U has opposing effects on cell proliferation and Wnt/beta-catenin signaling pathway activity compared to H19 and that hnRNP U is very important in this process. PMID- 26801865 TI - Comment on "Skin Manifestations of Chronic Kidney Disease". PMID- 26801866 TI - Behavioral Interventions for Preventing Sexually Transmitted Infections and Unintended Pregnancies: An Overview of Systematic Reviews. AB - BACKGROUND: Countless sex education programs have been implemented worldwide in recent decades, but epidemiological data show no improvement in rates of sexually transmitted infections or unintended pregnancies. OBJECTIVE: To summarize the evidence from higher-quality systematic reviews on the efficacy of behavioral interventions for the prevention of sexually transmitted infections and unintended pregnancies. METHODS: We conducted an overview of reviews by selecting systematic reviews that met minimum quality criteria in terms of the design of the studies reviewed. We compared the results obtained when the effects of interventions were assessed on the basis of objective criteria (biological data) to those obtained when outcomes were assessed on the basis of subjective criteria (self-reports). The results of Cochrane and non-Cochrane reviews were also compared. RESULTS: We identified 55 systematic reviews. No overall effect on the sexual behavior of program participants was observed in 72.5% of the reviews that used objective criteria and in 48.1% of the reviews based on subjective criteria. In the Cochrane reviews, no evidence of an overall effect was observed in 86% of reviews based on objective variables and in 70.5% of those based on subjective variables. CONCLUSIONS: There is no evidence that behavioral interventions modify rates of sexually transmitted infections (including human immunodeficiency virus infections) or unintended pregnancies, particularly when effects are assessed using objective, biological data. Primary prevention strategies for sexually transmitted infections and unintended pregnancies need to be re-evaluated. PMID- 26801867 TI - Tuberous Lesion of 1-Year Duration on the Knee. PMID- 26801868 TI - [(18) F]-Fluorodeoxy-d-glucose uptake-positive seborrhoeic keratosis on positron emission tomography may result from high expression of glucose transporter. AB - [(18) F]-Fluorodeoxy-d-glucose (FDG) positron emission tomography-computed tomography (PET-CT) is known to be highly accurate in differentiating benign lesions from malignant lesions. In rare cases, benign tumours, viral infections and sarcoidosis of the skin have been reported to show FDG uptake, but the mechanism remains unclear. Here we report the first documented case of seborrhoeic keratosis (SK) showing increased FDG uptake. FDG PET-CT can be used to detect enhanced glycolysis of tumour cells by measuring increased levels of glucose transporters (GLUTs) indicative of higher glucose uptake. GLUT1 and GLUT3 expression in this case was compared with that in PET-negative SK and two normal skin samples using quantitative polymerase chain reaction with paraffin-embedded tissue. The expression of GLUT1 and GLUT3 was higher in PET-positive SK than in PET-negative SK or normal skin. More specifically, the expression of GLUT3 was observed only in the PET-positive case. This study revealed that high GLUT1 and GLUT3 expression in SK might be associated with the uptake of FDG. PMID- 26801869 TI - Fibroblast growth factor receptor-1 protein expression is associated with prognosis in estrogen receptor-positive/human epidermal growth factor receptor-2 negative primary breast cancer. AB - Recently, research into the development of new targeted therapies has focused on specific genetic alterations to create advanced, more personalized treatment. One of the target genes, fibroblast growth factor receptor-1 (FGFR1), has been reported to be amplified in estrogen receptor (ER)-positive subtype breast cancer, and is considered one possible mechanism of endocrine resistance through cross-talk between ER and growth factor receptor signaling. We performed a comprehensive analysis of FGFR1 at the levels of gene copy number, transcript and protein expression, and examined the relationships between FGFR1 status and clinicopathological parameters, including prognosis in 307 ER-positive/HER2 negative primary breast cancer patients treated with standard care at our institute. Most notably, a high level of FGFR1 protein expression was observed in 85 patients (27.7%), and was positively associated with invasive tumor size (P = 0.039). Furthermore, univariate analysis revealed that high FGFR1 protein expression was significantly correlated with poor relapse-free survival rate (P = 0.0019, HR: 2.63, 95% confidence interval: 1.17-5.98), and showed a tendency towards an increase in recurrent events if the observation period extended beyond the 5 years of the standard endocrine treatment term. FGFR1 gain/amplification was found in 43 (14.0%) patients, which was only associated with higher nuclear grade (P = 0.010). No correlation was found between FGFR1 mRNA expression levels and any clinicopathological factors. Overall, the level of FGFR1 protein expression may be a biomarker of ER-positive/HER2-negative primary breast cancer with possible resistance to standard treatment, and may be a useful tool to identify more specific patients who would benefit from FGFR-1 targeted therapy. PMID- 26801870 TI - Prolonged duration of untreated psychosis: a problem that needs addressing. AB - AIM: The duration of untreated psychosis (DUP) refers to the period of time between the emergence of psychotic symptoms and the initiation of appropriate clinical treatment. Prolonged DUP is associated with a range of adverse consequences, including more severe illness course, cognitive deficits and poor functioning. Problems with recognition of illness and in seeking help contribute to DUP, but another major cause of prolonged DUP is delays within secondary mental health services. In an attempt to reduce these delays, National Health Service England and the Department of Health have set new targets to improve access to early intervention services which will come into effect in April 2016. Given this background, we aimed to examine the DUP and pathways to care of new patients entering an early intervention service. We also examined whether they were receiving National Institute for Health and Care Excellence (NICE) concordant treatment. This will enable us to establish a baseline so that the impact of the new targets can be determined and to assess the degree of change that will be required to implement these. METHODS: De-identified electronic records of 165 patients accepted into the service over a 12-month period were analysed. RESULTS: Median DUP was 6 months. There was a median of 2 contacts prior to service entry. Community Mental Health Teams were the largest source of referrals. CONCLUSIONS: The majority of patients had a DUP exceeding the international target of 3 months. The findings appear to support previous evidence that this may be partially attributable to significant delays within the mental health care system. PMID- 26801872 TI - Evolution of adaptation mechanisms: Adaptation energy, stress, and oscillating death. AB - In 1938, Selye proposed the notion of adaptation energy and published 'Experimental evidence supporting the conception of adaptation energy.' Adaptation of an animal to different factors appears as the spending of one resource. Adaptation energy is a hypothetical extensive quantity spent for adaptation. This term causes much debate when one takes it literally, as a physical quantity, i.e. a sort of energy. The controversial points of view impede the systematic use of the notion of adaptation energy despite experimental evidence. Nevertheless, the response to many harmful factors often has general non-specific form and we suggest that the mechanisms of physiological adaptation admit a very general and nonspecific description. We aim to demonstrate that Selye's adaptation energy is the cornerstone of the top-down approach to modelling of non-specific adaptation processes. We analyze Selye's axioms of adaptation energy together with Goldstone's modifications and propose a series of models for interpretation of these axioms. Adaptation energy is considered as an internal coordinate on the 'dominant path' in the model of adaptation. The phenomena of 'oscillating death' and 'oscillating remission' are predicted on the base of the dynamical models of adaptation. Natural selection plays a key role in the evolution of mechanisms of physiological adaptation. We use the fitness optimization approach to study of the distribution of resources for neutralization of harmful factors, during adaptation to a multifactor environment, and analyze the optimal strategies for different systems of factors. PMID- 26801871 TI - Challenges and opportunities for hydrogen production from microalgae. AB - The global population is predicted to increase from ~7.3 billion to over 9 billion people by 2050. Together with rising economic growth, this is forecast to result in a 50% increase in fuel demand, which will have to be met while reducing carbon dioxide (CO2 ) emissions by 50-80% to maintain social, political, energy and climate security. This tension between rising fuel demand and the requirement for rapid global decarbonization highlights the need to fast-track the coordinated development and deployment of efficient cost-effective renewable technologies for the production of CO2 neutral energy. Currently, only 20% of global energy is provided as electricity, while 80% is provided as fuel. Hydrogen (H2 ) is the most advanced CO2 -free fuel and provides a 'common' energy currency as it can be produced via a range of renewable technologies, including photovoltaic (PV), wind, wave and biological systems such as microalgae, to power the next generation of H2 fuel cells. Microalgae production systems for carbon based fuel (oil and ethanol) are now at the demonstration scale. This review focuses on evaluating the potential of microalgal technologies for the commercial production of solar-driven H2 from water. It summarizes key global technology drivers, the potential and theoretical limits of microalgal H2 production systems, emerging strategies to engineer next-generation systems and how these fit into an evolving H2 economy. PMID- 26801873 TI - A quantitative insight into metastatic relapse of breast cancer. AB - BACKGROUND: Metastatic relapse is the principal source of breast cancer mortality. This work seeks to uncover unobservable, yet clinically important, aspects of post-surgery metastatic relapse of breast cancer and to quantify effects of surgery on metastatic progression. METHODS: We classified metastases into three categories: (1) solitary cancer cells that were formed before or during surgery and either circulate in blood or are lodged at various secondary sites; (2) dormant or slowly growing avascular metastases; and (3) vascular secondary tumors. We developed a general mathematical model aimed at describing post-surgery dynamics of these three metastatic states. One parametric version of the model assumed that sojourn times of metastases in the three states are exponentially distributed while another was based on Erlang distribution. Model parameters were estimated from a sample of metastatic relapse or censoring times for 673 breast cancer patients treated with surgery. RESULTS: We estimated the expected number of metastases at surgery and mean sojourn times for the three states and found that both are decreasing with state number. We also computed the probability that metastatic relapse resulted from a metastasis in a given state at surgery. The values of these attribution probabilities suggest that under the Erlang model all three states have a considerable effect on metastatic relapse while in the case of exponential model this is true for states 1 and 2 only. CONCLUSIONS: (1) In some patients metastasis occurred before surgery; (2) our results confirm significance of metastatic dormancy; (3) according to the model surgery stimulates escape from dormancy, promotes angiogenesis and accelerates metastatic growth in a fraction of breast cancer patients. Taken summarily, these findings call into question the benefits of primary tumor resection for certain categories of breast cancer patients. PMID- 26801874 TI - A mathematical model for the induction of the mammalian ureteric bud. AB - Congenital abnormalities of the kidney and urinary tract collectively form the most common type of prenatally diagnosed malformations. Whilst many of the crucial genes that direct the kidney developmental program are known, the mechanisms by which kidney organogenesis is achieved is still largely unclear. In this paper, we propose a mathematical model for the localisation of the ureteric bud, the precursor to the ureter and collecting duct system of the kidney. The mathematical model presented fundamentally implicates Schnakenberg-like ligand receptor Turing patterning as the mechanism by which the ureteric bud is localised on the Wolfian duct as proposed by Menshykaul and Iber (2013). This model explores the specific roles of regulatory proteins GREM1 and BMP as well as the domain properties of GDNF production. Our model demonstrates that this proposed pattern formation mechanism is capable of naturally predicting the phenotypical outcomes of many genetic experiments from the literature. Furthermore, we conclude that whilst BMP inhibits GDNF away from the budding site and GREM1 permits GDNF to signal, GREM1 also stabilises the effect of BMP on GDNF signalling from fluctuations in BMP sensitivity but not signal strength. PMID- 26801875 TI - Balancing direct and indirect sources of navigational information in a leaderless model of collective animal movement. AB - Navigation is an important movement process that enables individuals and groups of animals to find targets in space at different spatio-temporal scales. Earlier studies have shown how being in a group can confer navigational advantages to individuals, either through following more experienced leaders or through the pooling of many inaccurate compasses, a process known as the 'many wrongs principle'. However, the exact mechanisms for how information is transferred and used within the group in order to improve both individual- and group-level navigational performance are not fully understood. Here we explore the relative weighting that should be given to different sources of navigational information by an individual within a navigating group at each step of the movement process. Specifically, we consider a direct goal-oriented source of navigational information such as the individual's own imperfect knowledge of the target (a 'noisy compass') alongside two indirect sources of navigational information: the previous movement directions of neighbours in the group (social information) and, for the first time in this context, the previous movement direction of the individual (persistence). We assume that all individuals are equal in their abilities and that direct navigational information is prone to higher errors than indirect information. Using computer simulations, we show that in such situations giving a high weighting to either type of indirect navigational information can serve to significantly improve the navigation success of groups. Crucially, we also show that if the quality of social information is reduced, e.g. by an individual's limited cognitive abilities, the best navigational strategy for groups assigns a considerable weighting to persistence, a behaviour that is neither social, nor directly aimed at navigating. PMID- 26801876 TI - Protein fold recognition using HMM-HMM alignment and dynamic programming. AB - Detecting three dimensional structures of protein sequences is a challenging task in biological sciences. For this purpose, protein fold recognition has been utilized as an intermediate step which helps in classifying a novel protein sequence into one of its folds. The process of protein fold recognition encompasses feature extraction of protein sequences and feature identification through suitable classifiers. Several feature extractors are developed to retrieve useful information from protein sequences. These features are generally extracted by constituting protein's sequential, physicochemical and evolutionary properties. The performance in terms of recognition accuracy has also been gradually improved over the last decade. However, it is yet to reach a well reasonable and accepted level. In this work, we first applied HMM-HMM alignment of protein sequence from HHblits to extract profile HMM (PHMM) matrix. Then we computed the distance between respective PHMM matrices using kernalized dynamic programming. We have recorded significant improvement in fold recognition over the state-of-the-art feature extractors. The improvement of recognition accuracy is in the range of 2.7-11.6% when experimented on three benchmark datasets from Structural Classification of Proteins. PMID- 26801877 TI - Osteoclastogenic differentiation of human precursor cells over micro- and nanostructured hydroxyapatite topography. AB - BACKGROUND: Surface topography is a key parameter in bone cells-biomaterials interactions. This study analyzed the behavior of human osteoclast precursor cells cultured over three hydroxyapatite (HA) surfaces ranging from a micro- to nanoscale topography. METHODS: HA surfaces were prepared with microsized HA particles, at 1300 degrees C (HA1), and with nanosized HA particles at 1000 degrees C (HA2) and 830 degrees C (HA3). Human osteoclast precursors were cultured in the absence or presence of M-SCF and RANKL. RESULTS: HA surfaces had similar chemical composition, however, HA1 and HA3 presented typical micro- and nanostructured topographies, respectively, and HA2 profile was between those of HA1 and HA3. The decrease on the average grain diameter to the nanoscale range (HA3) was accompanied by an increase in surface area, porosity and hydrophilicity and a decrease in roughness. Compared to HA1 surface, HA3 allowed a lower osteoclastic adhesion, differentiation and function. Differences in the cell response appeared to be associated with the modulation of relevant intracellular signaling pathways. CONCLUSIONS: The decrease in HA grain size to a biomimetic nanoscale range, appears less attractive to osteoclastic differentiation and function, compared to the HA microsized topography. GENERAL SIGNIFICANCE: This observation emphasizes the role of surface topography in designing advanced biomaterials for tailored bone cells response in regenerative strategies. PMID- 26801878 TI - The use of Gene Ontology terms and KEGG pathways for analysis and prediction of oncogenes. AB - BACKGROUND: Oncogenes are a type of genes that have the potential to cause cancer. Most normal cells undergo programmed cell death, namely apoptosis, but activated oncogenes can help cells avoid apoptosis and survive. Thus, studying oncogenes is helpful for obtaining a good understanding of the formation and development of various types of cancers. METHODS: In this study, we proposed a computational method, called OPM, for investigating oncogenes from the view of Gene Ontology (GO) and biological pathways. All investigated genes, including validated oncogenes retrieved from some public databases and other genes that have not been reported to be oncogenes thus far, were encoded into numeric vectors according to the enrichment theory of GO terms and KEGG pathways. Some popular feature selection methods, minimum redundancy maximum relevance and incremental feature selection, and an advanced machine learning algorithm, random forest, were adopted to analyze the numeric vectors to extract key GO terms and KEGG pathways. RESULTS: Along with the oncogenes, GO terms and KEGG pathways were discussed in terms of their relevance in this study. Some important GO terms and KEGG pathways were extracted using feature selection methods and were confirmed to be highly related to oncogenes. Additionally, the importance of these terms and pathways in predicting oncogenes was further demonstrated by finding new putative oncogenes based on them. CONCLUSIONS: This study investigated oncogenes based on GO terms and KEGG pathways. Some important GO terms and KEGG pathways were confirmed to be highly related to oncogenes. We hope that these GO terms and KEGG pathways can provide new insight for the study of oncogenes, particularly for building more effective prediction models to identify novel oncogenes. The program is available upon request. GENERAL SIGNIFICANCE: We hope that the new findings listed in this study may provide a new insight for the investigation of oncogenes. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang. PMID- 26801879 TI - Glycomics and glycoproteomics focused on aging and age-related diseases--Glycans as a potential biomarker for physiological alterations. AB - BACKGROUND: Since glycosylation depends on glycosyltransferases, glycosidases, and sugar nucleotide donors, it is susceptible to the changes associated with physiological and pathological conditions. Therefore, alterations in glycan structures may be good targets and biomarkers for monitoring health conditions. Since human aging and longevity are affected by genetic and environmental factors such as diseases, lifestyle, and social factors, a scale that reflects various environmental factors is required in the study of human aging and longevity. SCOPE OF REVIEW: We herein focus on glycosylation changes elucidated by glycomic and glycoproteomic studies on aging, longevity, and age-related diseases including cognitive impairment, diabetes mellitus, and frailty. We also consider the potential of glycan structures as biomarkers and/or targets for monitoring physiological and pathophysiological changes. MAJOR CONCLUSIONS: Glycan structures are altered in age-related diseases. These glycans and glycoproteins may be involved in the pathophysiology of these diseases and, thus, be useful diagnostic markers. Age-dependent changes in N-glycans have been reported previously in cohort studies, and characteristic N-glycans in extreme longevity have been proposed. These findings may lead to a deeper understanding of the mechanisms underlying aging as well as the factors influencing longevity. GENERAL SIGNIFICANCE: Alterations in glycosylation may be good targets and biomarkers for monitoring health conditions, and be applicable to studies on age-related diseases and healthy aging. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc. PMID- 26801881 TI - Localization of neutralization epitopes on adenovirus fiber knob from species C. AB - Although potential neutralization epitopes on the fiber knob of adenovirus (AdV) serotype 2 (Ad2) and Ad5 have been revealed, few studies have been carried out to identify neutralization epitopes on the knob from a broader panel of AdV serotypes. In this study, based on sequence and structural analysis of knobs from Ad1, Ad2, Ad5 and Ad6 (all from species C), several trimeric chimeric knob proteins were expressed in Escherichia coli to identify the locations of neutralization epitopes on the knobs by analysing their reactivity with mouse and rabbit polyclonal sera raised against AdVs and human sera with natural AdV infection. The dominant neutralization epitopes were located mainly in the N terminal part of knobs from Ad1, Ad2 and Ad5, but they seemed to be located in the C-terminal part of the Ad6 knob, with some individual differences in rabbit and human populations. Our study adds to our understanding of humoral immune responses to AdVs and will facilitate the construction of more desirable capsid modified recombinant Ad5 vectors. PMID- 26801880 TI - Inhibition of Akt Enhances the Chemopreventive Effects of Topical Rapamycin in Mouse Skin. AB - The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced nonmelanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared with those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events. Here, we explored the use of topical rapamycin as a chemopreventive agent in the context of solar-simulated light (SSL)-induced skin carcinogenesis. In SKH-1 mice, topical rapamycin treatment decreased tumor yields when applied after completion of 15 weeks of SSL exposure compared with controls. However, applying rapamycin during SSL exposure for 15 weeks, and continuing for 10 weeks after UV treatment, increased tumor yields. We also examined whether a combinatorial approach might result in more significant tumor suppression by rapamycin. We validated that rapamycin causes increased Akt (S473) phosphorylation in the epidermis after SSL, and show for the first time that this dysregulation can be inhibited in vivo by a selective PDK1/Akt inhibitor, PHT 427. Combining rapamycin with PHT-427 on tumor prone skin additively caused a significant reduction of tumor multiplicity compared with vehicle controls. Our findings indicate that patients taking rapamycin should avoid sun exposure, and that combining topical mTOR inhibitors and Akt inhibitors may be a viable chemoprevention option for individuals at high risk for cutaneous SCC. PMID- 26801882 TI - Sero-prevalence of Taenia spp. cysticercosis in rural and urban smallholder pig production settings in Uganda. AB - The pork tapeworm, Taenia solium, is prevalent in Uganda although the prevalence has not been determined in all areas of the country. A cross-sectional study, to determine the sero-prevalence of the parasite in pigs kept under rural and urban production settings, was carried out in three Ugandan districts, Masaka, Mukono and Kamuli. Serum samples from 1185 pigs were tested for the presence of T. solium cysticercosis antigen using the HP10 antigen-ELISA (Ag-ELISA) and the ApDia Ag-ELISA assays. Using parallel interpretation of the two tests showed lower levels of observed prevalence of T. solium in rural production settings (10.8%) compared to urban (17.1%). Additionally, Maximum Likelihood Estimation for evaluating assays in the absence of a gold standard, using TAGS on the R platform, estimated the true sero-prevalence to be lower in rural production setting, 0.0% [0.0-3.2%; 95% confidence interval (CI)] than in urban production setting, 12.3% (4.2-77.5% CI). When the sensitivity/specificity (Se/Sp) of the assays were estimated, assuming conditional independence of the tests, HP10 Ag ELISA was more sensitive and specific [(Se=53.9%; 10.1-100% CI), (Sp=97.0%; 95.9 100% CI)] than the ApDia assay [(Se=20.2%; 1.5-47.7% CI), (Sp=92.2%; 90.5-93.9% CI)]. Subject to parasitological verification, these results indicate there may be a need to implement appropriate control measures for T. solium in the study areas. PMID- 26801883 TI - Species composition and activity patterns of sand flies (Psycodidae: Phlebotomine) in four tehsils of Dir Districts, Khyber Pakhtunkhwa, Pakistan. AB - The present study reports sand flies species composition, fauna diversity and seasonal variations from four tehsils of Dir Districts, Khyber Pakhtunkhwa, Pakistan. Collection was made using sticky traps, flit method and aspiration where highest number of sand flies was captured through sticky traps. Digitalized sand flies distribution maps were produced using geographic information system ArcGIS. A total of 7292 specimens were captured between January to December 2014, comprised of 11 Sergentomyia and 9 Phlebotomus. Phlebotomus salengensis was the most abundant species followed by Phlebotomus sergenti. Overall, male to female ratio observed was 3:1 and species diversity varied among the studied tehsils. Highest abundance was recorded in July and August, whereas the flies disappeared in the colder months (November-April) of the year. Information about insect vector behaviour in natural setting is required to understand the status of disease caused by them. This study is a thorough account of biodiversity of sand flies in the region and provides a useful insight in to identifying potential breeding preferences of sand flies and recognition of active and potential vector species in the Dir districts. Further large scale studies are needed to determine the behaviour, infection rate, and the natural reservoir hosts of sand fly vectors in the region. PMID- 26801884 TI - Microbiome-based companion diagnostics: no longer science fiction? PMID- 26801885 TI - A randomised trial of endoscopic submucosal dissection versus endoscopic mucosal resection for early Barrett's neoplasia. AB - BACKGROUND: For endoscopic resection of early GI neoplasia, endoscopic submucosal dissection (ESD) achieves higher rates of complete resection (R0) than endoscopic mucosal resection (EMR). However, ESD is technically more difficult and evidence from randomised trial is missing. OBJECTIVE: We compared the efficacy and safety of ESD and EMR in patients with neoplastic Barrett's oesophagus (BO). DESIGN: BO patients with a focal lesion of high-grade intraepithelial neoplasia (HGIN) or early adenocarcinoma (EAC) <=3 cm were randomised to either ESD or EMR. Primary outcome was R0 resection; secondary outcomes were complete remission from neoplasia, recurrences and adverse events (AEs). RESULTS: There were no significant differences in patient and lesion characteristics between the groups randomised to ESD (n=20) or EMR (n=20). Histology of the resected specimen showed HGIN or EAC in all but six cases. Although R0 resection defined as margins free of HGIN/EAC was achieved more frequently with ESD (10/17 vs 2/17, p=0.01), there was no difference in complete remission from neoplasia at 3 months (ESD 15/16 vs EMR 16/17, p=1.0). During a mean follow-up period of 23.1+/-6.4 months, recurrent EAC was observed in one case in the ESD group. Elective surgery was performed in four and three cases after ESD and EMR, respectively (p=1.0). Two severe AEs were recorded for ESD and none for EMR (p=0.49). CONCLUSIONS: In terms of need for surgery, neoplasia remission and recurrence, ESD and EMR are both highly effective for endoscopic resection of early BO neoplasia. ESD achieves a higher R0 resection rate, but for most BO patients this bears little clinical relevance. ESD is, however, more time consuming and may cause severe AE. TRIAL REGISTRATION NUMBER: NCT1871636. PMID- 26801886 TI - Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma. AB - OBJECTIVE: Recent data supports a significant role for immune checkpoint inhibitors in the treatment of solid tumours. Here, we evaluate gastric and gastro-oesophageal junction (G/GEJ) adenocarcinomas for their expression of programmed death-ligand 1 (PD-L1), infiltration by CD8+ T cells and the relationship of both factors to patient survival. DESIGN: Thirty-four resections of primary invasive G/GEJ were stained by immunohistochemistry for PD-L1 and CD8 and by DNA in situ hybridisation for Epstein-Barr virus (EBV). CD8+ T cell densities both within tumours and at the tumour-stromal interface were analysed using whole slide digital imaging. Patient survival was evaluated according to PD L1 status and CD8 density. RESULTS: 12% of resections showed tumour cell membranous PD-L1 expression and 44% showed expression within the immune stroma. Two cases (6%) were EBV positive, with one showing membranous PD-L1 positivity. Increasing CD8+ densities both within tumours and immune stroma was associated with increasing percentage of tumour (p=0.027) and stromal (p=0.005) PD-L1 expression. Both tumour and immune stromal PD-L1 expression and high intratumoral or stromal CD8+ T cell density (>500/mm2) were associated with worse progression free survival (PFS) and overall survival (OS). CONCLUSIONS: PD-L1 is expressed on both tumour cells and in the immune stroma across all stages and histologies of G/GEJ. Surprisingly, we demonstrate that increasing CD8 infiltration is correlated with impaired PFS and OS. Patients with higher CD8+ T cell densities also have higher PD-L1 expression, indicating an adaptive immune resistance mechanism may be occurring. Further characterisation of the G/GEJ immune microenvironment may highlight targets for immune-based therapy. PMID- 26801887 TI - Raf kinase inhibitor protein mediates intestinal epithelial cell apoptosis and promotes IBDs in humans and mice. AB - OBJECTIVE: Raf kinase inhibitor protein (RKIP) appears to control cancer cell metastasis and its expression in colonic tissue is related to colonic cancer development. We sought to identify the roles of RKIP in maintaining homeostasis of GI tract. DESIGN: The expression of RKIP was determined by immunohistochemistry and western blot analysis. RKIP knockout and wild-type mice were administered dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis, and the mice were assessed based on colitis symptoms and biochemical approaches. The mechanism was analysed using immunoprecipitation and pull-down experiments. RESULTS: The RKIP expression is positively correlated with the severity of IBD. RKIP deficiency protects mice from DSS-induced or TNBS-induced colitis and accelerated recovery from colitis. RKIP deficiency inhibits DSS-induced infiltration of acute-phase immune cells and reduces production of proinflammatory cytokines and chemokines in colon. RKIP deficiency inhibits DSS-induced or TNBS-induced colonic epithelial barrier damage and intestinal epithelial cell (IEC) apoptosis. RKIP deficiency also inhibits tumour necrosis factor-alpha-induced IEC apoptosis and colitis. Mechanistically, RKIP enhances the induction of P53-upregulated modulator of apoptosis by interacting with TGF-beta-activated kinase 1 (TAK1) and promoting TAK1-mediated NF-kappaB activation. This is supported by the observation that TAK1 activation is positively correlated with the expression of RKIP in human clinical samples and the development of IBD. CONCLUSIONS: RKIP contributes to colitis development by promoting inflammation and mediating IEC apoptosis and might represent a therapeutic target of IBD. PMID- 26801888 TI - Effect of two viscosity models on lethality estimation in sterilization of liquid canned foods. AB - A numerical study on 2D natural convection in cylindrical cavities during the sterilization of liquid foods was performed. The mathematical model was established on momentum and energy balances and predicts both the heating dynamics of the slowest heating zone (SHZ) and the lethal rate achieved in homogeneous liquid canned foods. Two sophistication levels were proposed in viscosity modelling: 1) considering average viscosity and 2) using an Arrhenius type model to include the effect of temperature on viscosity. The remaining thermodynamic properties were kept constant. The governing equations were spatially discretized via orthogonal collocation (OC) with mesh size of 25 * 25. Computational simulations were performed using proximate and thermodynamic data for carrot-orange soup, broccoli-cheddar soup, tomato puree, and cream-style corn. Flow patterns, isothermals, heating dynamics of the SHZ, and the sterilization rate achieved for the cases studied were compared for both viscosity models. The dynamics of coldest point and the lethal rate F0 in all food fluids studied were approximately equal in both cases, although the second sophistication level is closer to physical behavior. The model accuracy was compared favorably with reported sterilization time for cream-style corn packed at 303 * 406 can size, predicting 66 min versus an experimental time of 68 min at retort temperature of 121.1 C. PMID- 26801889 TI - [The age effect in evaluation of hearing aid benefits by speech audiometry]. AB - BACKGROUND AND AIM: Hearing loss is one of the most common disabilities in the elderly. The aim of this study was to investigate the relationship between pure tone hearing loss and maximum monosyllabic perception and speech perception with hearing aids. The focus of the investigation was elderly patients. MATERIALS AND METHODS: In this prospective study, 188 patients with sensorineural hearing loss were included. The pure-tone audiogram (4FPTA), the Freiburg speech intelligibility test with headphones and the word recognition score with hearing aids at 65 dB SPL were measured and evaluated. RESULTS: An increasing age was associated with higher discrepancy between the maximum speech perception and speech understanding with hearing aids. The mean difference between maximum monosyllabic perception and speech perception with hearing aids is about 20% in the elderly population. CONCLUSION: The intended goal of hearing aid prescription, the match between maximum monosyllabic perception and word recognition score with hearing aids within 5 to 10%, is not achieved in the elderly population. PMID- 26801890 TI - [Caution after premature discharge against medical advice: More responsibility- less money]. PMID- 26801891 TI - [The new hospital admissions policy : SHI-Contracted doctors between recourse and liability]. PMID- 26801892 TI - [The new eHealth legislation : What lies ahead for hospitals and doctors in private practice?]. PMID- 26801893 TI - Patients to test whether new technologies help manage conditions. PMID- 26801894 TI - The dual role of Andean topography in primary divergence: functional and neutral variation among populations of the hummingbird, Metallura tyrianthina. AB - BACKGROUND: The ridges and valleys of the Andes create physical barriers that limit animal dispersal and cause deterministic local variation in rainfall. This has resulted in physical isolation of animal populations and variation in habitats, each of which has likely contributed to the evolution of high species diversity in the region. However, the relative influences of geographic isolation, ecoclimatic conditions, and their potential interactions remain poorly understood. To address this, we compared patterns of genetic and morphological diversity in Peruvian populations of the hummingbird Metallura tyrianthina. RESULTS: Phylogenetic and variation partitioning analyses showed that geographic isolation rather than climatic dissimilarity explained the greatest proportion of genetic variance. In contrast, bill length variation was explained by climatic seasonality, but not by genetic divergence. We found that mutation-scaled migration rate (m) between persistently humid and semi-humid environments was nearly 20 times higher when the habitats were contiguous (m = 39.9) than when separated by a barrier, the Cordillera de Vilcanota (m = 2.1). Moreover, the population experiencing more gene flow exhibited a lesser degree of bill length divergence despite similar differences in climate. CONCLUSIONS: Geographic isolation is necessary for genetic divergence. Ecological differences, represented here by climate characteristics, are necessary for functional divergence. Gene flow appears to hinder the evolution of functional traits toward local adaptive optima. This suggests that functional diversification requires geographic isolation followed or accompanied by a shift in ecological conditions. Andean topography causes both isolation and climatic variation, underscoring its dual role in biotic diversification. PMID- 26801897 TI - Intergenerational Transfer of Epigenetic Information in Sperm. AB - The inheritance of information beyond DNA sequence, known as epigenetic inheritance, has been implicated in a multitude of biological processes from control of plant flowering time to cancer in humans. In addition to epigenetic inheritance that occurs in dividing cells of a multicellular organism, it is also increasingly clear that at least some epigenetic information is transmitted via the gametes in a multitude of organisms, including mammals. Here, I review the evidence for epigenetic information carriers in mammalian sperm, and explore the emerging field of intergenerational transfer of environmental information. PMID- 26801898 TI - Use of complementary and alternative medicine in patients with health complaints attributed to former dental amalgam fillings. AB - BACKGROUND: The dental filling material amalgam is generally well tolerated. However, a small proportion of dental patients experience health complaints which they attribute to amalgam. The symptom pattern is often similar to patients with medically unexplained physical symptoms (MUPS) and the health complaints may persist after amalgam removal. Among patients with MUPS, the use of complementary and alternative medicine (CAM) seems to be high. The aim of this survey was to describe the prevalence and range of CAM use among people with health complaints attributed to dental amalgam fillings in which the health problems persist after the removal of all amalgam fillings. Specific attention was paid to (1) self reported effects of CAM, (2) differences in CAM use dependent on self-reported health, and (3) gender differences in self-reported CAM use. METHODS: A survey was distributed to all members of The Norwegian dental patient association (NDPA) (n = 999), the response rate was 36.4%. The anonymous questionnaire asked for socio-demographic data, health complaints related to former amalgam fillings, subjectively perceived health status, symptoms, and experience with therapeutic interventions, mostly from the spectrum of CAM. Only participants who had all their fillings removed, which was the vast majority, were analysed. RESULTS: A total of 88.9% of included respondents had used at least one CAM modality, with a higher proportion of men (95.7%) compared to women (86.2%, p = 0.015). The most frequently used therapies were dietary supplements, vitamins and minerals recommended by a therapist (used by 66.7%) followed by self-prescribed dietary supplements, vitamins and minerals (59.0%), homeopathy (54.0%), acupuncture (48.8%) and special diets (47.5%). Use of CAM was similar for participants reporting normal to good health compared to participants reporting poor health. For all but two CAM modalities, the self-reported treatment effect was better in the group reporting normal to good health compared to the group reporting poor health. CONCLUSIONS: CAM was widely used by participants in our study, a finding similar to findings from studies of MUPS patients. To date, health problems associated with the use of dental amalgam is not an accepted diagnosis in the healthcare system. Consequently, people suffering from such complaints experience a lack of adequate treatment and support within conventional health care, which might have contributed to the high number of CAM users in this study. PMID- 26801896 TI - p53 Isoforms: Key Regulators of the Cell Fate Decision. AB - It is poorly understood how a single protein, p53, can be responsive to so many stress signals and orchestrates very diverse cell responses to maintain/restore cell/tissue functions. The uncovering that TP53 gene physiologically expresses, in a tissue-dependent manner, several p53 splice variants (isoforms) provides an explanation to its pleiotropic biological activities. Here, we summarize a decade of research on p53 isoforms. The clinical studies and the diverse cellular and animal models of p53 isoforms (zebrafish, Drosophila, and mouse) lead us to realize that a p53-mediated cell response is, in fact, the sum of the intrinsic activities of the coexpressed p53 isoforms and that unbalancing expression of different p53 isoforms leads to cancer, premature aging, (neuro)degenerative diseases, inflammation, embryo malformations, or defects in tissue regeneration. Cracking the p53 isoforms' code is, thus, a necessary step to improve cancer treatment. It also opens new exciting perspectives in tissue regeneration. PMID- 26801895 TI - Mechanisms of Action of Antiseizure Drugs and the Ketogenic Diet. AB - Antiseizure drugs (ASDs), also termed antiepileptic drugs, are the main form of symptomatic treatment for people with epilepsy, but not all patients become free of seizures. The ketogenic diet is one treatment option for drug-resistant patients. Both types of therapy exert their clinical effects through interactions with one or more of a diverse set of molecular targets in the brain. ASDs act by modulation of voltage-gated ion channels, including sodium, calcium, and potassium channels; by enhancement of gamma-aminobutyric acid (GABA)-mediated inhibition through effects on GABAA receptors, the GABA transporter 1 (GAT1) GABA uptake transporter, or GABA transaminase; through interactions with elements of the synaptic release machinery, including synaptic vesicle 2A (SV2A) and alpha2delta; or by blockade of ionotropic glutamate receptors, including alpha amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors. The ketogenic diet leads to increases in circulating ketones, which may contribute to the efficacy in treating pharmacoresistant seizures. Production in the brain of inhibitory mediators, such as adenosine, or ion channel modulators, such as polyunsaturated fatty acids, may also play a role. Metabolic effects, including diversion from glycolysis, are a further postulated mechanism. For some ASDs and the ketogenic diet, effects on multiple targets may contribute to activity. Better understanding of the ketogenic diet will inform the development of improved drug therapies to treat refractory seizures. PMID- 26801899 TI - Sexual violence and general functioning among formerly abducted girls in Northern Uganda: the mediating roles of stigma and community relations--the WAYS study. AB - BACKGROUND: Although sexual violence in war is associated with long-term mental health problems, little is known about its association with general functioning and the factors that explain this association. This study aims to illuminate the path from sexual violence to poor functioning. The prevalence of sexual violence among formerly abducted girls in Northern Uganda was assessed as well as the extent to which stigma and community relations explain the association between sexual violence and general functioning. METHOD: In a cross-sectional analysis using data from the WAYS study (N = 210, baseline age 22.06, SD = 2.06, minimum maximum 18-25), the extent of mediation of the association between sexual violence and general functioning was assessed in multiple regression models. RESULTS: Sexual violence was found to be associated with increased stigma, poor community relations, and poor general functioning. The association between sexual violence and general functioning was mediated by stigma and community relations. The bootstrap results indicated significant mediation by stigma of 47 % (95 % confidence interval [CI] 35 to 78 % and by community relations of 67 % (95 % CI: 52 to 78 %) in the association between sexual violence and general functioning. CONCLUSION: Thus, poor functioning among formerly abducted girls is largely mediated by stigma and poor community relations. However, due to the relatively small effect sizes of the associations, targeted interventions to prevent impaired functioning may have only modest benefits to the formerly abducted girls. Interventions to alleviate the toxic effects of sexual violence in formerly abducted girls would benefit from a holistic approach that targets stigma and poor relationships within communities. PMID- 26801900 TI - Pharmacogenetics driving personalized medicine: analysis of genetic polymorphisms related to breast cancer medications in Italian isolated populations. AB - BACKGROUND: Breast cancer is the most common cancer in women characterized by a high variable clinical outcome among individuals treated with equivalent regimens and novel targeted therapies. In this study, we performed a population based approach intersecting high-throughput genotype data from Friuli Venezia Giulia (FVG) isolated populations with publically available pharmacogenomics information to estimate the frequency of genotypes correlated with responsiveness to breast cancer treatment thus improving the clinical management of this disease in an efficient and cost effective way. METHODS: A list of 80 variants reported to be related to the efficacy or toxicity of breast cancer drugs was obtained from PharmGKB database. Fourty-one were present in FVG, 1000G European (EUR) and ExAC (Non Finnish European) databases. Their frequency was extracted using PLINK software and the differences tested by Fisher's exact test. RESULTS: Statistical analyses revealed that 13 out of the 41 (32 %) variants were significantly different in frequency in our sample as compared to the EUR/ExAC cohorts. For nine variants the available level of evidence (LOE) included polymorphisms related to cyclophosphamide, tamoxifen, doxorubicin, fluorpyrimidine and paclitaxel. In particular, for trastuzumab two variants were detected: (1) rs1801274-G within FCGR2A and associated with decreased efficacy (LOE 2B); (2) rs1136201-G located within ERBB2 and associated with increased toxicity (LOE 3). Both these two variants were underrepresented in the FVG population compared to EUR/ExAC population thus suggesting a high therapeutic index of this drug in our population. Moreover, as regards fluoropyrimidines, the frequency of two polymorphisms within the DPYD gene associated with drug toxicity (e.g., rs2297595 C allele and rs3918290-T allele, LOE 2A and 1, respectively) was extremely low in FVG population thus suggesting that a larger number of FVG patients could benefit from full dosage of fluoropyrimidine therapy. CONCLUSIONS: All these findings increase the overall knowledge on the prevalence of specific variants related with breast cancer treatment responsiveness in FVG population and highlight the importance of assessing gene polymorphisms related with cancer medications in isolated communities. PMID- 26801903 TI - Gender-specific contributing risk factors and outcome of female cryptococcal meningoencephalitis patients. AB - BACKGROUND: Although male predominance was documented in previous studies on cryptococcal meningoencephalitis (CM), there has been no statistical study about female CM patients despite recently noticeable increase in female prevalence. In the current study, we aimed to investigate the independent gender-specific contributing risk factors for onset of CM and factors related to survival time in female patients by chosen statistical tools. METHODS: There have been 108 patients diagnosed with CM from July 1, 1998 to June 30, 2013 in Nanfang Hospital that were included in our study. This 15-year retrospective study compared demographic and clinical features of 31 female patients with 77 males. Multivariate analysis was performed for detection of the contributors to the onset of CM in female patients. The independent variables for multivariate analysis were selected according to statistical significance in univariate analysis. Furthermore, Cox regression model was used to evaluate the factors related to survival length. RESULTS: Use of corticosteroids or other immunosuppressants (32.3% versus 11.7%; p = 0.011) and history of systemic lupus erythematosus (SLE) and other autoimmune diseases (29% versus 3.9%; p < 0.001) were more common in females, but only the history of SLE or other autoimmune diseases was significant (OR 10.59, 95% CI 1.49-74.77, p = 0.02) by multivariate analysis. The ratio of cerebrospinal fluid (CSF) glucose-to-blood glucose was related to the survival time (p = 0.03, 95% CI 0-0.71). CONCLUSIONS: The results showed that the history of SLE or other autoimmune diseases rather than chronic use of corticosteroids and/or immunosuppressants was the independent gender specific contributing risk factor in female CM patients. Therefore, more attention should be made to the prevention of infection from the genus Cryptococcus spp. in female patients with SLE or other autoimmune diseases. In addition, decreased ratio of CSF glucose-to-blood glucose before antifungal therapy predicted the worse prognosis. PMID- 26801904 TI - Relevance of frozen sections and serum markers in invasive squamous cell carcinoma arising from ovarian mature cystic teratoma: two case reports. AB - BACKGROUND: Ovarian mature cystic teratoma (MCT) is a common neoplasm in women. While malignant transformation of MCT is relatively rare, squamous cell carcinoma is the most frequent malignant neoplasm arising from MCT. Some tumor markers have been reported to be useful for prediction of MCT malignant transformation prior to operation. However, widely accepted use of these markers remains to be established. In the present study, we report the usefulness of frozen section assessment during operation, as well as preoperative measurement of tumor marker levels. CASE PRESENTATION: We present two cases of squamous cell carcinoma arising from ovarian MCT. The first case was a 45-year-old Asian woman referred to our hospital after her periodical company medical checkup, due to possible ovarian tumor. Image analysis suggested a dermoid cyst, and left salpingo oophorectomy was performed. Because the cyst was histologically diagnosed as an invasive squamous cell carcinoma arising from an MCT, our patient underwent an additional preventative operation. The TNM classification and FIGO stage were T1aNXM0 and Ia, respectively. The second case was a 53 -year-old Asian woman who visited our hospital due to complaints of abdominal pain and urinary retention. Image analysis and laboratory data showing high serum levels of SCC antigen (normal range: < 1.5 ng/mL) and CA19-9 (normal range: < 37 U/mL), which strongly suggested malignant transformation of MCT. Frozen sections obtained during the operation were histologically analyzed to confirm malignancy, and our patient underwent an additional operation. The TNM classification and FIGO stage were T1aNXM0 and Ia, respectively. CONCLUSIONS: We report the usefulness of frozen section assessment during operation, as well as preoperative measurement of tumor marker levels. PMID- 26801901 TI - The critical care management of poor-grade subarachnoid haemorrhage. AB - Aneurysmal subarachnoid haemorrhage is a neurological syndrome with complex systemic complications. The rupture of an intracranial aneurysm leads to the acute extravasation of arterial blood under high pressure into the subarachnoid space and often into the brain parenchyma and ventricles. The haemorrhage triggers a cascade of complex events, which ultimately can result in early brain injury, delayed cerebral ischaemia, and systemic complications. Although patients with poor-grade subarachnoid haemorrhage (World Federation of Neurosurgical Societies 4 and 5) are at higher risk of early brain injury, delayed cerebral ischaemia, and systemic complications, the early and aggressive treatment of this patient population has decreased overall mortality from more than 50% to 35% in the last four decades. These management strategies include (1) transfer to a high volume centre, (2) neurological and systemic support in a dedicated neurological intensive care unit, (3) early aneurysm repair, (4) use of multimodal neuromonitoring, (5) control of intracranial pressure and the optimisation of cerebral oxygen delivery, (6) prevention and treatment of medical complications, and (7) prevention, monitoring, and aggressive treatment of delayed cerebral ischaemia. The aim of this article is to provide a summary of critical care management strategies applied to the subarachnoid haemorrhage population, especially for patients in poor neurological condition, on the basis of the modern concepts of early brain injury and delayed cerebral ischaemia. PMID- 26801902 TI - Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines. AB - BACKGROUND: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30% response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this study was to lay the groundwork for development of predictive biomarkers for irinotecan treatment in BC. METHODS: We established BC cell lines with acquired or de novo resistance to SN-38, by exposing the human BC cell lines MCF-7 and MDA-MB-231 to either stepwise increasing concentrations over 6 months or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer resistance protein (ABCG2/BCRP) drug efflux pump. RESULTS: We found that the resistant cell lines showed 7-100 fold increased resistance to SN-38 but remained sensitive to docetaxel and the non-camptothecin Top1 inhibitor LMP400. The resistant cell lines were characterized by Top1 down-regulation, changed isoelectric points of Top1 and reduced growth rates. The gene and protein expression of ABCG2/BCRP was up regulated in the resistant sub-lines and functional assays revealed BCRP as a key mediator of SN-38 resistance. CONCLUSIONS: Based on our preclinical results, we suggest analyzing the predictive value of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan. PMID- 26801905 TI - Dexketoprofen/tramadol 25 mg/75 mg: randomised double-blind trial in moderate-to severe acute pain after abdominal hysterectomy. AB - BACKGROUND: Dexketoprofen trometamol plus tramadol hydrochloride is a new oral combination of two analgesics, which have different mechanisms of action for the treatment of moderate to severe acute pain. METHODS: Randomised, double-blind, parallel, placebo and active-controlled, single and multiple-dose study to evaluate the analgesic efficacy and safety of dexketoprofen/tramadol 25 mg/75 mg in comparison with the single agents (dexketoprofen 25 mg and tramadol 100 mg) in moderate to severe acute pain after abdominal hysterectomy. Patients received seven consecutive doses of study drug within a 3-day period, each dose separated by an 8-hour interval. A placebo arm was included during the single-dose phase to validate the pain model. Efficacy assessments included pain intensity, pain relief, patient global evaluation and use of rescue medication. The primary endpoint was the mean sum of pain intensity differences over the first 8 h (SPID8). RESULTS: The efficacy analysis included 606 patients, with a mean age of 48 years (range 25-73). The study results confirmed the superiority of the combination over the single agents in terms of the primary endpoint (p <0.001). Secondary endpoints were generally supportive of the superiority of the combination for both single and multiple doses. Most common adverse drug reactions (ADRs) were nausea (4.6%) and vomiting (2.3%). All other ADRs were experienced by less than 2% of patients. CONCLUSIONS: The study results provided robust evidence of the superiority of dexketoprofen/tramadol 25 mg/75 mg over the single components in the management of moderate to severe acute pain, as confirmed by the single-dose efficacy, repeated-dose sustained effect and good safety profile observed. TRIAL REGISTRATION: EU Clinical Trials Register (EudraCT number 2012-004545-32, registered 04 October 2012); Clinicaltrials.gov ( NCT01904149, registered 17 July 2013). PMID- 26801907 TI - Correction. PMID- 26801906 TI - Using vignettes to assess contributions to the work of addressing child mental health problems in primary care. AB - BACKGROUND: To further efforts to integrate mental health and primary care, this study develops a novel approach to quantifying the amount and sources of work involved in shifting care for common mental health problems to pediatric primary care providers. METHODS: Email/web-based survey of a convenience sample (n = 58) of Maryland pediatricians (77% female, 58% at their site 10 or more years; 44% in private practice, 52 % urban, 48 % practicing with a co-located mental health provider). Participants were asked to review 11 vignettes, which described primary care management of child/youth mental health problems, and rate them on an integer-based ordinal scale for the overall amount of work involved compared to a 12th reference vignette describing an uncomplicated case of ADHD. Respondents were also asked to indicate factors (time, effort, stress) accounting for their ratings. Vignettes presented combinations of three diagnoses (ADHD, anxiety, and depression) and three factors (medical co-morbidity, psychiatric co morbidity, and difficult families) reported to complicate mental health care. The reference case was pre-assigned a work value of 2. Estimates of the relationship of diagnosis and complicating factors with workload were obtained using linear regression, with random effects at the respondent level. RESULTS: The 58 pediatricians gave 593 vignette responses. Depression was associated with a 1.09 unit (about 50%) increase in work (95% CL .94, 1.25), while anxiety did not differ significantly from the reference case of uncomplicated ADHD (p = .28). Although all three complicating factors increased work ratings compared with the reference case, family complexity and psychiatric co-morbidity did so the most (.87 and 1.07 units, respectively, P < .001) while medical co-morbidity increased it the least (.44 units, p < .001). Factors most strongly associated with increased overall work were physician time, physician mental effort, and stress; those least strongly associated were staff time, physician physical effort, and malpractice risk. Pediatricians working with co-located mental health providers gave higher work ratings than did those without co-located staff. CONCLUSIONS: Both diagnosis and cross-diagnosis complicating factors contribute to the work involved in providing mental health services in primary care. Vignette studies may facilitate understanding which mental health services can be most readily incorporated into primary care as it is presently structured and help guide the design of training programs and other implementation strategies. PMID- 26801908 TI - Estimating the impact of changes in HbA1c, body weight and insulin injection regimen on health related quality-of-life: a time trade off study. AB - BACKGROUND: There are limited data on the potential short-term benefits associated with reductions in HbA1c levels, and understanding any immediate improvements in health related quality-of-life (HRQoL) through better glycaemic control may help inform diabetes management decisions. This time-trade-off (TTO) study investigated the short-term impact on HRQoL associated with three different aspects of diabetes management; HbA1c change, body weight change, and the complexity of treatment regimen. METHODS: The study was designed in three stages: Stage 1) Qualitative telephone interviews with people with type 2 diabetes (T2D) in Denmark who had experienced a decrease in their HbA1c level. Stage 2) A validation survey with people with T2D in Denmark to obtain quantifiable knowledge on the short-term effects of a change in HbA1c levels. Stage 3) TTO survey using health states based on results from stage 2. Respondents were either adults with T2D (Sweden) or from the general public (UK and Denmark) and were separately asked to evaluate seven health states through an internet-based survey. RESULTS: Results from 4060 respondents were available for the TTO analysis (UK n = 1777; Denmark n = 1799, Sweden n = 484). 'Well-controlled diabetes' was associated with utilities of 0.85-0.91 and 'not well-controlled diabetes' with utilities of 0.71-0.80 in all countries. Difference in utilities per HbA1c percentage point was smallest in Sweden and largest in Denmark (between 0.025-0.034 per HbA1c percentage point respectively). The treatment management health state associated with the lowest disutility was the once-daily insulin regimen. The disutility associated with per kg of weight change ranged from 0.0041-0.0073. CONCLUSIONS: Changes in HbA1c levels, insulin regimen and body weight are all likely to affect HRQoL for patients with T2D. A change in HbA1c is likely to have a short-term impact in addition to the effect on the development of long term diabetes complications. A treatment which has a simple regimen with fewer injections, and/or the need for less planning, and that causes weight loss or less weight gain, compared with other treatments, will have a positive impact on HRQoL. PMID- 26801909 TI - Lack of K13 mutations in Plasmodium falciparum persisting after artemisinin combination therapy treatment of Kenyan children. AB - BACKGROUND: Studies in Southeast Asia reported a strong relationship between polymorphisms at the propeller domain of the Kelch 13 (K13) protein encoded by the Plasmodium falciparum k13 (pfk13) gene and delayed parasite clearance after artemisinin treatment. In Africa, P. falciparum remains susceptible and combination therapy regimens which include an artemisinin component display good efficacy. Using quantitative real-time PCR (qPCR), sub-microscopic persistence of P. falciparum has previously been reported in one-third of children treated with artemisinin combination therapy (ACT) in western Kenya. In this study, further investigation was made to evaluate whether these sub-microscopic residual parasites also harbour mutations at the propeller region of pfk13 and whether the mutations, if any, affect treatment outcome. METHODS: The pfk13 propeller domain was genotyped in DNA samples obtained in 2009 from Kenyan children treated with artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Paired samples at pre-treatment (day 0) and day of treatment failure (day 28 or 42) for 32 patients with documented recurrent parasitaemia were available for genotyping. Additional day 3 DNA samples were available for 10 patients. RESULTS: No mutation associated with artemisinin resistance in Southeast Asia was observed. Only one DP-treated patient harboured a non-synonymous mutation at codon 578 (A578S) of pfk13-propeller gene in the day 0 sample, but this allele was replaced by the wild-type (A578) form on day 3 and on the day of recurrent parasitaemia. The mutation at amino acid codon 578 showed no association with any phenotype. Polymorphisms in pfk13 were not responsible for parasite persistence and gametocyte carriage in the children treated with ACT. CONCLUSION: This study contributes to the ongoing surveillance of suspected artemisinin resistance parasites in Africa by providing baseline prevalence of k13-propeller mutations in western Kenya with samples collected from a longitudinal study. Clinical Trials Registration NCT00868465. PMID- 26801910 TI - Targeted antitumor prodrug therapy using CNGRC-yCD fusion protein in combination with 5-fluorocytosine. AB - BACKGROUND: The enzyme-prodrug system is considered a promising tool for tumor treatment when conjugated with a targeting molecule. The asparagine-glycine arginine (NGR) motif is a developing and interesting targeting peptide that could specifically bind to aminopeptidase N (APN), which is an NGR receptor expressed on the cell membrane of angiogenic endothelial cells and a number of tumor cells within the tumor tissues. The objective of this study was to develop a novel targeted enzyme-prodrug system using 5-fluorocytosine (5-FC) and an NGR containing peptide fused with yeast cytosine deaminase (yCD), i.e. CNGRC-yCD fusion protein, to target APN-expressing cells within the tumor tissues and to convert 5-FC into 5-fluorouracil (5-FU) to kill tumors. RESULTS: Both yCD and CNGRC-yCD proteins were cloned into the pET28a vector and expressed by an Escherichia coli host. Both yCD and CNGRC-yCD proteins were purified and the yields were approximately 20 mg/L with over 95 % purity. The binding assay demonstrated that the CNGRC-yCD fusion protein had specific binding affinity toward purified APN recombinant protein and high-APN-expressing cells, including human endothelial cells (HUVECs) and various types of human tumor cell lines, but not low-APN-expressing tumor cell lines. Moreover, the enzyme activity and cell viability assay showed that the CNGRC-yCD fusion protein could effectively convert 5-FC into 5-FU and resulted in significant cell death in both high-APN expressing tumor cells and HUVECs. CONCLUSIONS: This study successfully constructs a new targeting enzyme-prodrug system, CNGRC-yCD fusion protein/5-FC. Systematic experiments demonstrated that the CNGRC-yCD protein retained both the APN-binding affinity of NGR and the enzyme activity of yCD to convert 5-FC into 5 FU. The combined treatment of the CNGRC-yCD protein with 5-FC resulted in the significantly increased cell death of high-APN-expressing cells as compared to that of low-APN-expressing cells. PMID- 26801911 TI - Single-stage in situ suture repair of multiple-ligament knee injury: a retrospective study of 17 patients (18 knees). AB - BACKGROUND: Multiple-ligament injured knee (MLIK) is a rare but severe injury. Although the principles of MLIK management have progressed over the past 40 years, there is a paucity of high-quality evidence upon which to base the management of MLIK. Treatment strategies for MLIK are challenging for most orthopedic surgeons, and the optimal treatment remains controversial, especially with regard to repair vs. reconstruction of the ligaments. The aim of the present study was to observe clinical outcomes of single-stage in situ suture repair of knee dislocation with multiple-ligament injury using nonabsorbable suture material. METHODS: Consecutive patients with MLIK between 2002 and 2010 were included, for a total of 25 patients with knee dislocation. 17 patients (18 knees) with closed knee dislocation with a mean follow-up of 4.8 +/- 1.3 years were retrospective analyzed. All patients were treated surgically with single stage in situ suture repair for all injured ligaments and followed a standardized postoperative rehabilitation protocol. The VAS score, satisfactory score, total SF-36 score, Lysholm score, Tegner score, the Meyers functional rating and the ranges of motion and knee stability were used to evaluate outcomes. RESULTS: At final follow-up, mean visual analog scale score was 2.4 +/- 0.9, patient satisfaction score was 8.0 +/- 1.1, 36-item Short-Form Health Survey total score was 85.5 +/- 10.4, and mean Lysholm score was 87.5 +/- 7.7. There were significant differences between mean preinjury and postoperative Tegner activity scores (5.6 +/- 1.4 and 3.4 +/- 1.7, respectively; P < 0.01) and in mean range of motion between the injured and contralateral knees (112.5 +/- 8.4 degrees and 129.6 +/- 10.3 degrees , respectively; P < 0.01). At final follow-up, no patient demonstrated obvious ligamentous laxity, and only one patient was unable to return to work. Three patients had knee joint stiffness, two had wound problems (infection or fat liquefaction), and two had heterotopic bone formation. CONCLUSIONS: Single-stage in situ suture repair of injured ligaments confers advantages of reliable fixation and early exercise. It could be considered as an alternate and effective option in the dislocation knee with multiple-ligament injury. PMID- 26801912 TI - Age at Surgery and Outcomes of an Undescended Testis. AB - BACKGROUND: Undescended testis (UDT) is the most common genital anomaly in boys. Current guidelines recommend surgery before 12 months of age to maximize fertility and potentially reduce the risk of future malignancy. We investigated the prevalence of UDT and examined rates of surgery and age at surgery in an Australian population. METHODS: UDT was identified from all live-born infants in New South Wales, Australia, from 2001 to 2011 using routinely collected record linked birth and hospital data. The prevalence of UDT, surgery rates, age at surgery, postsurgical outcomes, and risk factors for surgery performed later than the recommended age were evaluated. RESULTS: There were 10 875 (2.1%) boys with a recorded diagnosis of UDT. Corrective surgery was performed in 4980 (45.8%), representing a cumulative prevalence of 9.6 per 1000 male births. Five percent of surgeries were orchidectomies, and 9% of boys had revision surgery. Median age at surgery was 16.6 months (interquartile range 11.8 to 31.0 months), decreasing from 21 months for boys born in 2001 to 13 months for boys born in 2010. Among those boys having surgery before 36 months (n = 3897), 67% had corrective surgery after the recommended 12 months of age; socioeconomic disadvantage, regional/remote area of residence, and lack of private health insurance were risk factors for having corrective surgery after 12 months. CONCLUSIONS: One in 50 boys born are diagnosed with UDT; two-thirds had no report of corrective surgery. The age at surgery is decreasing; however, two-thirds of surgeries are performed after 12 months of age. PMID- 26801913 TI - Provision of Preventive Dental Services in Children Enrolled in Medicaid by Nondental Providers. AB - OBJECTIVES: Aims of this study are to determine (1) the association of oral health services (OHS) provided by nontraditional providers with the percentage of Medicaid children 0 to 5 years of age who receive >=1 preventive services from all provider types in the United States; and (2) characteristics of state Medicaid policies associated with provision of OHS. METHODS: We conducted a time series cross-sectional study of preventive services provided by nontraditional (OHS) and dental (PDS) providers for Medicaid-enrolled children from birth to 5 years of age in all states during 2010 to 2013 (204 observations). We applied panel data multiple regression analysis techniques to exploit year and state variation in aggregate data available in Centers for Medicare and Medicaid Services reports (form CMS-416). Total preventive dental services (TPDS =OHS + PDS) was predicted by months since state enactment of a policy to reimburse medical providers for OHS. RESULTS: The 44 states with a policy reported 4.3% of children per state per year with any OHS. For all states, an average of 30.1% received PDS and 34.5% TPDS. The delivery of OHS was associated with a small increase in percentage with TPDS. One year of Medicaid OHS availability was associated with an increase of 1.5% in the percentage of children with TPDS per state per year. CONCLUSIONS: Implementation of policies by Medicaid programs to support integration of OHS into primary care is associated with increases in overallTPDS use, but efforts are needed to improve implementation in practice to achieve national impact on access. PMID- 26801914 TI - Classroom Standing Desks and Sedentary Behavior: A Systematic Review. AB - CONTEXT: Reducing sedentary behaviors, or time spent sitting, is an important target for health promotion in children. Standing desks in schools may be a feasible, modifiable, and acceptable environmental strategy to this end. OBJECTIVE: To examine the impact of school-based standing desk interventions on sedentary behavior and physical activity, health-related outcomes, and academic and behavioral outcomes in school-aged children. DATA SOURCES: Ovid Embase, Medline, PsycINFO, Web of Science, Global Health, and CINAHL. STUDY SELECTION: Full-text peer-reviewed journal publications written in English; samples of school-aged youth (5-18 years of age); study designs including the same participants at baseline and follow-up; and use of a standing desk as a component of the intervention. DATA EXTRACTION: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Eight studies satisfied selection criteria and used quasi-experimental (n = 4), randomized controlled trial (n = 3), and pre-post, no control (n = 1) designs. When examined, time spent standing increased in all studies (effect sizes: 0.38-0.71), while sitting time decreased from a range of 59 to 64 minutes (effect sizes: 0.27-0.49). Some studies reported increased physical activity and energy expenditure and improved classroom behavior. LIMITATIONS: One-half of the studies had nonrandomized designs, and most were pilot or feasibility studies. CONCLUSIONS: This initial evidence supports integrating standing desks into the classroom environment; this strategy has the potential to reduce sitting time and increase standing time among elementary schoolchildren. Additional research is needed to determine the impact of standing desks on academic performance and precursors of chronic disease risk. PMID- 26801915 TI - Biogenic selenium nanoparticles: current status and future prospects. AB - Selenium nanoparticles (SeNPs) are gaining importance in the field of medicine owing to their antibacterial and anticancer properties. SeNPs are biocompatible and non-toxic compared to the counterparts, selenite (SeO3 (-2)) and selenate (SeO4 (-2)). They can be synthesized by physical, chemical, and biological methods and have distinct bright orange-red color. Biogenic SeNPs are stable and do not aggregate owing to natural coating of the biomolecules. Various hypotheses have been proposed to describe the mechanism of microbial synthesis of SeNPs. It is primarily a two-step reduction process from SeO4 (-2) to SeO3 (-2) to insoluble elemental selenium (Se(0)) catalyzed by selenate and selenite reductases. Phenazine-1-carboxylic acid and glutathione are involved in selenite reduction. Se factor A (SefA) and metalloid reductase Rar A present on the surface of SeNPs confer stability to the nanoparticles. SeNPs act as potent chemopreventive and chemotherapeutic agents. Conjugation with antibiotics enhances their anticancer efficacy. These also have applications in nanobiosensors and environmental remediation. PMID- 26801917 TI - Oxidative stress level in fresh ejaculate is not related to semen parameters or to pregnancy rates in cycles with donor oocytes. AB - PURPOSE: The purpose of the present study is to study the relationship between oxidative stress (OS) in semen, semen characteristics, and reproductive outcomes in oocyte donation intracytoplasmic sperm injection (ICSI) cycles. METHODS: OS was measured in 132 semen samples. RESULTS: OS levels were as follows: very high (1.5 %), high (43.2 %), low (30.3 %), and very low (25.0 %). Overall seminal parameters were as follows: volume (ml) = 4.2 (SD 2.1), concentration (millions/ml) = 61.6 (SD 59.8), motility (a+b%) = 47.4 (SD 18.0), and normal spermatozoa (%) = 8.2 (SD 5.1). Of the 101 cycles that reached embryo transfer, 55.4 % evolved in biochemical, 46.5 % in clinical, and 43.6 % in ongoing pregnancy. OS level does not relate to seminal parameters, fertilization rate, or pregnancy outcomes. CONCLUSIONS: OS testing by nitro blue tetrazolium (NBT) in fresh ejaculate might not be useful for all patients. Reproductive results with young oocytes and ICSI do not seem to be affected by OS-level semen. PMID- 26801916 TI - Stroke Symptoms With Absence of Recognized Stroke Are Associated With Cognitive Impairment and Depressive Symptoms in Older Adults With Diabetes. AB - Self-reported stroke symptoms may represent unrecognized cerebrovascular events leading to poorer cognitive and mental health. We examined relationships between stroke symptoms, cognitive impairment, and depressive symptoms in a high-risk sample: 247 adults aged >=65 with diabetes. Stroke symptoms were assessed using the Questionnaire for Verifying Stroke-free Status, cognitive impairment was measured with the modified Telephone Interview for Cognitive Status, and depressive symptoms were measured using the 15-item Geriatric Depression Scale. In 206 participants without history of stroke/transient ischemic attack, 27.7% reported stroke symptoms, with sudden loss of comprehension most frequently reported (11.7%). Having >1 versus 0 stroke symptoms was associated with greater odds of cognitive impairment (odds ratio = 3.04, 95% confidence interval 1.15 8.05) and more depressive symptoms (b= 2.60,P< .001) while controlling for age, race, gender, education, diabetes duration, diabetes severity, and cardiovascular comorbidities. Better recognition and treatment of cerebrovascular problems in older adults with diabetes may lead to improved cognition and mental health. PMID- 26801918 TI - Comprehensive Profile of Cardiopulmonary Exercise Testing in Ambulatory Persons with Multiple Sclerosis. AB - BACKGROUND: The study and application of exercise in multiple sclerosis (MS) often requires cardiopulmonary exercise testing (CPET) to provide a comprehensive assessment of exercise tolerance and responses, including an evaluation of the pulmonary, cardiovascular, and skeletal muscle systems. Research on CPET in persons with MS has considerable limitations, including small sample sizes, often without controls; not reporting outcomes across disability status; and different modalities of exercise testing across studies. Although some key outcome variables of CPET have been studied in persons with MS, additional calculated variables have not been directly studied. OBJECTIVE: The objective of this study was to provide a comprehensive examination of outcome variables from CPET among persons with MS and healthy controls. METHODS: We included data from 162 persons with MS and 80 healthy controls who underwent CPET on a leg ergometer and satisfied criteria for valid testing for measuring oxygen uptake (VO2), carbon dioxide production (VCO2), ventilation (VE), respiratory exchange ratio, work rate, and heart rate (HR). Calculated variables [i.e. ventilatory anaerobic threshold (VO2/VCO2), VE/VCO2 slope, VO2/power slope, VO2/HR slope, and oxygen uptake efficiency slope] were processed using standard guidelines. We examined differences in the CPET variables between groups (e.g. MS vs. controls and categories of mild, moderate, and severe disability status) using analysis of covariance (ANCOVA), controlling for age, sex, body mass index, and disease duration. RESULTS: Overall, persons with MS demonstrate alterations in outcomes from CPET compared with controls, and these are generally exacerbated with increasing disability. CONCLUSION: Our results provide novel information for the evaluation of CPET in MS for developing exercise prescriptions and documenting adaptations with exercise training based on the comprehensive variables obtained during CPET. PMID- 26801920 TI - Competitive Exclusion and Axiomatic Set-Theory: De Morgan's Laws, Ecological Virtual Processes, Symmetries and Frozen Diversity. AB - This work applies the competitive exclusion principle and the concept of potential competitors as simple axiomatic tools to generalized situations in ecology. These tools enable apparent competition and its dual counterpart to be explicitly evaluated in poorly understood ecological systems. Within this set theory framework we explore theoretical symmetries and invariances, De Morgan's laws, frozen evolutionary diversity and virtual processes. In particular, we find that the exclusion principle compromises the geometrical growth of the number of species. By theoretical extending this principle, we can describe interspecific depredation in the dual case. This study also briefly considers the debated situation of intraspecific competition. The ecological consequences of our findings are discussed; particularly, the use of our framework to reinterpret coupled mathematical differential equations describing certain ecological processes. PMID- 26801919 TI - Exosomes Secreted by Apoptosis-Resistant Acute Myeloid Leukemia (AML) Blasts Harbor Regulatory Network Proteins Potentially Involved in Antagonism of Apoptosis. AB - Expression of apoptosis-regulating proteins (B-cell CLL/lymphoma 2 - BCL-2, Myeloid Cell Leukemia 1 - MCL-1, BCL-2 like 1 - BCL-X and BCL-2-associated X protein - BAX) in acute myeloid leukemia (AML) blasts at diagnosis is associated with disease-free survival. We previously found that the initially high apoptosis resistance of AML cells decreased after therapy, while regaining high levels at relapse. Herein, we further explored this aspect of dynamic apoptosis regulation in AML. First, we showed that the intraindividualex vivoapoptosis-related profiles of normal lymphocytes and AML blasts within the bone marrow of AML patients were highly correlated. The expression values of apoptosis-regulating proteins were far beyond healthy control lymphocytes, which implicates the influence of microenvironmental factors. Second, we demonstrated that apoptosis resistant primary AML blasts, as opposed to apoptosis-sensitive cells, were able to up-regulate BCL-2 expression in sensitive AML blasts in contact cultures (p= 0.0067 andp= 1.0, respectively). Using secretome proteomics, we identified novel proteins possibly engaged in apoptosis regulation. Intriguingly, this analysis revealed that major functional protein clusters engaged in global gene regulation, including mRNA splicing, protein translation, and chromatin remodeling, were more abundant (p= 4.01E-06) in secretomes of apoptosis-resistant AML. These findings were confirmed by subsequent extracellular vesicle proteomics. Finally, confocal-microscopy-based colocalization studies show that splicing factors-containing vesicles secreted by high AAI cells are taken up by low AAI cells. The current results constitute the first comprehensive analysis of proteins released by apoptosis-resistant and sensitive primary AML cells. Together, the data point to vesicle-mediated release of global gene regulatory protein clusters as a plausible novel mechanism of induction of apoptosis resistance. Deciphering the modes of communication between apoptosis-resistant blasts may in perspective lead to the discovery of prognostic tools and development of novel therapeutic interventions, aimed at limiting or overcoming therapy resistance. PMID- 26801921 TI - Hybrid Tibia Fixation of Soft Tissue Grafts in Anterior Cruciate Ligament Reconstruction: A Systematic Review. AB - BACKGROUND: Optimal fixation of soft tissue grafts in anterior cruciate ligament (ACL) reconstruction remains a controversial topic, and tibial-sided fixation is frequently cited as the "weak point" of the femur-graft-tibia construct. Some studies have recommended the use of hybrid fixation (combining intratunnel aperture fixation and extracortical suspensory fixation) on the tibial side to increase the strength of the reconstructed ACL and decrease the risk of graft slippage and subsequent failure. However, no consensus has emerged on the necessity or suitability of this technique, relative to single modes of fixation. PURPOSE: This study sought answers to the following questions: (1) Does hybrid fixation result in stronger, stiffer initial fixation of soft tissue grafts? (2) Does hybrid fixation reduce side-to-side laxity differences in clinical practice? (3) Does hybrid fixation increase complication rates when compared with a single mode of tibial fixation? STUDY DESIGN: Systematic review. METHODS: A systematic keyword search of PubMed, EMBASE, the Cochrane Library of Systematic Reviews, and the PROSPERO International Prospective Register of Systematic Reviews was performed. Candidate articles were included if they compared biomechanical or clinical characteristics of tibial-sided hybrid fixation (defined as a combination of aperture and suspensory fixation methods) with single-mode fixation of soft tissue grafts in ACL reconstruction. RESULTS: A total of 21 studies (15 biomechanical, 6 clinical) met criteria for inclusion. Most biomechanical studies reported significantly increased strength and stiffness with hybrid fixation versus single modes of fixation. Among clinical studies, 66% reported significantly decreased anterior-posterior laxity when hybrid fixation methods were employed, with the remainder showing no difference. CONCLUSION: Hybrid methods of tibial-sided graft fixation in ACL reconstruction result in stronger initial fixation and less side-to-side laxity after healing but do not change patient-reported outcomes at 1- to 3-year follow-up. REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews No. 42014015464. PMID- 26801922 TI - The Degree of Knee Extension Does Not Affect Postoperative Stability or Subsequent Graft Tear Rate After Anterior Cruciate Ligament Reconstruction With Patellar Tendon Autograft. AB - BACKGROUND: There is concern that high degrees of hyperextension may lead to an increase in graft laxity or graft failure after anterior cruciate ligament (ACL) reconstruction. HYPOTHESIS: Patients with a high degree of hyperextension will have a higher rate of graft tear/failure and lower subjective scores after surgery compared with patients with less knee extension. STUDY DESIGN: Cohort study, Level of evidence, 2. METHODS: Of 2329 patients who underwent ACL reconstruction with patellar tendon autograft between 1998 and 2008, there were 625 patients who met the inclusion criteria of having primary ACL surgery, no bilateral ACL injuries, no existing osteoarthritis, and having either >=6 degrees of knee hyperextension before and after surgery (group A: n = 318; mean hyperextension, 8 degrees +/- 2 degrees [range, 6 degrees -15 degrees ]) or <=3 degrees of knee hyperextension before and after surgery (group B: n = 307; mean hyperextension, 0 degrees +/- 3 degrees [range, 3 degrees hyperextension to -4 degrees short of 0 degrees neutral]). KT-1000 arthrometer manual maximum difference between knees, range of motion measurements, and subjective follow-up with International Knee Documentation Committee (IKDC) and Cincinnati Knee Ratings Scale (CKRS) surveys were used to evaluate results. Subsequent graft tear related to specific injury within 5 years of surgery was recorded. Graft failure was defined as a KT-1000 manual maximum difference of >5 mm. RESULTS: Follow-up was obtained from 278 (87%) in group A and 275 (90%) in group B at a mean of 4.1 +/- 1.1 years after surgery. The KT-1000 arthrometer manual maximum difference between knees was 2.0 +/- 1.4 in group A and 2.1 +/- 1.6 in group B (P = .701). Subsequent ACL graft tear/failure occurred in 22 patients (6.9%) in group A and 30 patients (9.8%) in group B (P = .246). Further subanalysis showed that the graft tear/failure rate was 6 of 81 (7.4%) for patients with >=10 degrees of hyperextension versus 16 of 237 (6.8%) for patients with 6 degrees to 9 degrees of hyperextension. There was no difference in IKDC or CKRS scores between groups after surgery (P = .933 and .155, respectively). CONCLUSION: Obtaining full hyperextension that is anatomically normal for most patients does not affect objective stability, ACL graft tear/failure rates, or subjective scores after ACL reconstruction with patellar tendon autograft. PMID- 26801923 TI - The Effect of an Orthopaedic Surgical Procedure in the National Basketball Association. AB - BACKGROUND: Professional basketball players have a high incidence of injuries requiring surgical intervention. However, no studies in the current literature have compared postoperative performance outcomes among common injuries to determine high- and low-risk procedures to these athletes' careers. PURPOSE: To compare return-to-play (RTP) rates and performance-based outcomes after different orthopaedic procedures in National Basketball Association (NBA) players and to determine which surgeries are associated with the worst postoperative change in performance. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Athletes in the NBA undergoing anterior cruciate ligament reconstruction, Achilles tendon repair, lumbar discectomy, microfracture, meniscus surgery, hand/wrist or foot fracture fixation, and shoulder stabilization were identified through team injury reports and archives on public record. The RTP rate, games played per season, and player efficiency rating (PER) were determined before and after surgery. Statistical analysis was used to compare the change between pre- and postsurgical performance among the different injuries. RESULTS: A total of 348 players were included. The RTP rates were highest in patients with hand/wrist fractures (98.1%; mean age, 27.0 years) and lowest for those with Achilles tears (70.8%; mean age, 28.4 years) (P = .005). Age >=30 years (odds ratio [OR], 3.85; 95% CI, 1.24-11.91) and body mass index >=27 kg/m(2) (OR, 3.46; 95% CI, 1.05-11.40) were predictors of not returning to play. Players undergoing Achilles tendon repair and arthroscopic knee surgery had a significantly greater decline in postoperative performance outcomes at the 1- and 3-year time points and had shorter career lengths compared with the other procedures. CONCLUSION: NBA players undergoing Achilles tendon rupture repair or arthroscopic knee surgery had significantly worse performance postoperatively compared with other orthopaedic procedures. PMID- 26801924 TI - Biological-waste as resource, with a focus on food waste. PMID- 26801925 TI - Autochthonous bioaugmentation with environmental samples rich in hydrocarbonoclastic bacteria for bench-scale bioremediation of oily seawater and desert soil. AB - Oil-contaminated seawater and desert soil batches were bioaugmented with suspensions of pea (Pisum sativum) rhizosphere and soil with long history of oil pollution. Oil consumption was measured by gas-liquid chromatography. Hydrocarbonoclastic bacteria in the bioremediation batches were counted using a mineral medium with oil vapor as a sole carbon source and characterized by their 16S ribosomal RNA (rRNA)-gene sequences. Most of the oil was consumed during the first 2-4 months, and the oil-removal rate decreased or ceased thereafter due to nutrient and oxygen depletion. Supplying the batches with NaNO3 (nitrogen fertilization) at a late phase of bioremediation resulted in reenhanced oil consumption and bacterial growth. In the seawater batches bioaugmented with rhizospheric suspension, the autochthonous rhizospheric bacterial species Microbacterium oxidans and Rhodococcus spp. were established and contributed to oil-removal. The rhizosphere-bioaugmented soil batches selectively favored Arthrobacter nitroguajacolicus, Caulobacter segnis, and Ensifer adherens. In seawater batches bioaugmented with long-contaminated soil, the predominant oil removing bacterium was the marine species Marinobacter hydrocarbonoclasticus. In soil batches on the other hand, the autochthonous inhabitants of the long contaminated soil, Pseudomonas and Massilia species were established and contributed to oil removal. It was concluded that the use of rhizospheric bacteria for inoculating seawater and desert soil and of bacteria in long contaminated soil for inoculating desert soil follows the concept of "autochthonous bioaugmentation." Inoculating seawater with bacteria in long contaminated soil, on the other hand, merits the designation "allochthonous bioaugmentation." PMID- 26801926 TI - Erratum to: Quantitatively evaluating detoxification of the hepatotoxic microcystin-LR through the glutathione (GSH) pathway in SD rats. PMID- 26801927 TI - Effects of exogenous calcium and spermidine on cadmium stress moderation and metal accumulation in Boehmeria nivea (L.) Gaudich. AB - Cadmium (Cd) is a detrimental metal in the environment and it is easily taken up by plants, thus entering the food chain and posing a severe threat to human health. Phytoremediation being low cost, highly stable, and environmentally friendly has been considered as a promising green technology for Cd remediation. The addition of exogenous substances to the culture media has been recognized as an efficient strategy to improve plant phytoremediation capability. Pot trials were conducted to investigate the combined effects of exogenous calcium (Ca) and spermidine (Spd) on Cd-induced toxicity in Boehmeria nivea (L.) Gaudich. (ramie). Results showed that the application of 5-mM exogenous Ca significantly alleviated Cd toxicity in ramie by reducing Cd accumulation, depressing H2O2 and malondialdehyde contents, increasing plants dry weights and chlorophyll concentrations, as well as altering the activities of total superoxide dismutase and guaiacol peroxidase. Furthermore, as a non-Cd hyperaccumulator plant, ramie hyperaccumulated Cd and suffered more severe toxic effects of Cd by the treatment of 1 mM Ca/Cd. The aggravated Cd toxicity could be compensated by the addition of exogenous Spd via the promotion of plant growth and the reduction of the oxidative stress. Overall, the combination effects of 1 mM Ca and Spd appeared to be more superior compared to other treatments in the plants under Cd stress with a higher Cd accumulation ability and the evaluated Cd stress tolerance. PMID- 26801928 TI - Heavy metal speciation and risk assessment in dry land and paddy soils near mining areas at Southern China. AB - Heavy metal contamination of soils has been a long-standing environmental problem in many parts of the world, and poses enormous threats to ecosystem and human health. Speciation of heavy metals in soils is crucial to assessing environmental risks from contaminated soils. In this study, total concentrations and speciation of As, Cd, Cr, Cu, Mn, Ni, Pb, and Zn were measured for agricultural soils near mines along the Diaojiang River in Guangxi Zhuang Autonomy Region, China. The sources of heavy metals in soils also were identified to assess their effect on speciation distribution of soil heavy metals. Furthermore, the speciation distribution of Cd and Zn, main soil heavy metal pollutants, in dry land and paddy soils were compared. Results showed that there were two severely polluted regions near mine area reaching alarming pollution level. As, Cd, Pb, and Zn were more affected by mining activities, showing very strong pollution level in soils. The mean percentage of exchangeable and carbonate fraction was highest and up to 46.8 % for Cd, indicating a high environmental risk. Greater bioavailable fractions of As, Cd, Cu, Mn, Pb, and Zn were found in soils heavily polluted by mining activities, whereas Cr and Ni as geogenic elements in the stable residual fraction. In addition, in the dry land soils, reducible fraction proportion of Cd was higher than that in the paddy soils, whereas exchangeable and carbonate fraction of Cd was lower than that in the paddy soils. Oxidizable fraction of Zn was higher in the paddy soils than that in the dry land soils. The results indicate that the sources of soil heavy metals and land types affect heavy metal speciation in the soil and are significant for environmental risk assessment of soil heavy metal pollutions. PMID- 26801929 TI - Characterization of soluble microbial products in a drinking water biological aerated filter. AB - Utilization-associated products (UAPs) and biomass-associated products (BAPs) were quantified separately in this study to characterize soluble microbial products (SMPs) in a drinking water lab-scale biological aerated filter (BAF), and their basic characteristics were explored using gel filtration chromatography and three-dimensional excitation-emission matrix (3D-EEM) spectrophotometry with fluorescence regional integration analysis and parallel factor model. UAPs were observed increased with the increase of filter media depth and accumulated after BAF treatment, whereas BAPs were basically constant. 3D-EEM spectroscopy analysis result showed that tryptophan and protein-like compounds were the main components of UAPs and BAPs, and fulvic-acid-like substance was a major component of BAPs, rather than UAPs. In terms of molecular weight (MW) distribution, UAP MW presented a bimodal distribution in the range of 1-5 and >10 kDa, while BAP MW exhibited unimodal distribution with MW >20 kDa fraction accounting for more than 90 %. The macromolecules of UAPs accumulated after BAF treatment. This study provides theoretical support for in-depth study of SMP characteristics. PMID- 26801930 TI - Comparative trends in incident fracture rates for all long-term care and community-dwelling seniors in Ontario, Canada, 2002-2012. AB - SUMMARY: In this population-based study, we compared incident fracture rates in long-term care (LTC) versus community seniors between 2002 and 2012. Hip fracture rates declined more rapidly in LTC than in the community. An excess burden of fractures occurred in LTC for hip, pelvis, and humerus fractures in men and hip fractures only in women. INTRODUCTION: This study compares trends in incident fracture rates between long-term care (LTC) and community-dwelling seniors >=65 years, 2002-2012. METHODS: This is a population-based cohort study using administrative data. Measurements were age/sex-adjusted incident fracture rates and rate ratios (RR) and annual percent change (APC). RESULTS: Over 11 years, hip fracture rates had a marked decline occurring more rapidly in LTC (APC, -3.49 (95% confidence interval (CI), -3.97, -3.01)) compared with the community (APC, 2.93 (95% CI, -3.28, -2.57); p < 0.05 for difference in slopes). Humerus and wrist fracture rates decreased; however, an opposite trend occurred for pelvis and spine fractures with rates increasing over time in both cohorts (all APCs, p < 0.05). In 2012, incident hip fracture rates were higher in LTC than the community (RRs: women, 1.55 (95% CI, 1.45, 1.67); men, 2.18 (95% CI, 1.93, 2.47)). Higher rates of pelvis (RR, 1.48 (95% CI, 1.22, 1.80)) and humerus (RR, 1.40 (95% CI, 1.07, 1.84)) fractures were observed in LTC men, not women. In women, wrist (RR, 0.76 (95% CI, 0.71, 0.81)) and spine (RR, 0.52 (95% CI, 0.45, 0.61)) fracture rates were lower in LTC than the community; in men, spine (RR, 0.75 (95% CI, 0.57, 0.98) but not wrist fracture (RR, 0.91 (95% CI, 0.67, 1.23)) rates were significantly lower in LTC than the community. CONCLUSION: Previous studies in the community have shown declining hip fracture rates over time, also demonstrated in our study but at a more rapid rate in LTC. Rates of humerus and wrist fractures also declined. An excess burden of fractures in LTC occurred for hip fractures in women and for hip, pelvis, and humerus fractures in men. PMID- 26801931 TI - Barriers to Recruitment and Adherence in a Randomized Controlled Diet and Exercise Weight Loss Intervention Among Minority Breast Cancer Survivors. AB - Minority recruitment to cancer trials is low and there are limited data on minority adherence to lifestyle modification interventions. We examined factors related to recruitment and adherence to a pilot weight loss intervention among Hispanic and black breast cancer survivors. Participants completed a detailed screening interview to assess barriers to enrollment. An index was created to assess adherence at 6 months. 112 potentially eligible women were identified; 66 consented and completed a screening interview. After screening, 9 were ineligible; 15 opted to not enroll; and 42 were randomized. Among eligible women, earlier stage at diagnosis, treatment type, and negative beliefs related to exercise and diet after diagnosis were negatively associated with study enrollment (P < 0.05). Self-reported barriers to adherence included fatigue, family responsibilities, illness, work, transportation, and negative perceptions of exercise and diet. Results from this study emphasize the need to adapt recruitment and adherence strategies to address these factors. PMID- 26801933 TI - Total shoulder arthroplasty: are the humeral components getting shorter? AB - Each generation of total shoulder arthroplasy has improved on the previous. The newest humeral component innovation is shortening the humeral component or eliminating the stem entirely to rely on stemless fixation in the humeral metaphysis. This offers theoretical advantages of preserved bone stock, less stress shielding, eliminating the diaphyseal stress riser, ease of stem removal at revision, and humeral head placement independent from the humeral shaft axis. There are a number of short term cohorts that have shown low complication rates and outcomes similar to previous generations of stemmed humeral components. Longer term and better designed studies are needed in order for short stems and stemless components to become the standard of care. PMID- 26801932 TI - The value of serum creatine kinase in predicting the risk of rhabdomyolysis induced acute kidney injury: a systematic review and meta-analysis. AB - INTRODUCTION: Identifying the potential effective factors of rhabdomyolysis induced acute kidney injury (AKI) is of major importance for both treatment and logistic concerns. The present study aimed to evaluate the value of creatine kinase (CK) in predicting the risk of rhabdomyolysis-induced AKI through meta analysis. METHODS: Two reviewers searched the electronic databases of Medline, EMBASE, Cochrane library, Scopus, and Google Scholar. Data regarding study design, patient characteristics, number of cases, mean and screening characteristics of CK, and final patient outcome were extracted from relevant studies. Pooled measures of standardized mean difference, OR, and diagnostic accuracy were calculated using STATA version 11.0. RESULT: 5997 non-redundant studies were found (143 potentially relevant). 27 articles met the inclusion criteria but 9 were excluded due to lack of data. The correlation between serum CK and AKI occurrence was stronger in traumatic cases (SMD = 1.34, 95 % CI = 1.25 1.42, I(2) = 94 %; p < 0.001). This correlation was more prominent in crush induced AKI (adjusted OR = 14.7, 95 % CI = 7.63-28.52, I(2) = 0.0 %; p = 0.001). Area under the ROC curve of CK in predicting AKI occurrence was 0.75 (95 % CI = 0.71-0.79). CONCLUSION: The results of this meta-analysis declared the significant role of rhabdomyolysis etiology (traumatic/non-traumatic) in predictive performance of CK. There was a significant correlation between mean CK level and risk of crush-induced AKI. The pooled OR of CK was considerable, but its screening performance characteristics were not desirable. PMID- 26801935 TI - The Yeast ATF1 Acetyltransferase Efficiently Acetylates Insect Pheromone Alcohols: Implications for the Biological Production of Moth Pheromones. AB - Many moth pheromones are composed of mixtures of acetates of long-chain (>=10 carbon) fatty alcohols. Moth pheromone precursors such as fatty acids and fatty alcohols can be produced in yeast by the heterologous expression of genes involved in insect pheromone production. Acetyltransferases that subsequently catalyze the formation of acetates by transfer of the acetate unit from acetyl CoA to a fatty alcohol have been postulated in pheromone biosynthesis. However, so far no fatty alcohol acetyltransferases responsible for the production of straight chain alkyl acetate pheromone components in insects have been identified. In search for a non-insect acetyltransferase alternative, we expressed a plant-derived diacylglycerol acetyltransferase (EaDAcT) (EC 2.3.1.20) cloned from the seed of the burning bush (Euonymus alatus) in a yeast system. EaDAcT transformed various fatty alcohol insect pheromone precursors into acetates but we also found high background acetylation activities. Only one enzyme in yeast was shown to be responsible for the majority of that background activity, the acetyltransferase ATF1 (EC 2.3.1.84). We further investigated the usefulness of ATF1 for the conversion of moth pheromone alcohols into acetates in comparison with Ea DAcT. Overexpression of ATF1 revealed that it was capable of acetylating these fatty alcohols with chain lengths from 10 to 18 carbons with up to 27- and 10-fold higher in vivo and in vitro efficiency, respectively, compared to Ea DAcT. The ATF1 enzyme thus has the potential to serve as the missing enzyme in the reconstruction of the biosynthetic pathway of insect acetate pheromones from precursor fatty acids in yeast. PMID- 26801937 TI - New studies about the insertion mechanism of Thymosin alpha1 in negative regions of model membranes as starting point of the bioactivity. AB - Thymosin alpha1 is a peptidic hormone already used in the therapy of several diseases. Until now, the description of the precise receptor and mechanism for its action still remains elusive. The interaction of Thymosin alpha1, which is unstructured in water solution, has been recently studied in sodium dodecylsulphate micellar systems and it was reported that Thymosin alpha1 inserts in micelle assuming a conformation with two tracts of helix with a structural break in between. An investigation of its interaction both with micelles of dodecylphosphocholine alone and with mixed dodecylphosphocholine-sodium dodecylsulphate micelles is here reported. In these environments the results indicate that Thymosin alpha1 in phospholipidic membrane exposing choline polar heads interacts by aspecific modality and, oppositely, in the mixed dodecylphosphocholine-sodium dodecylsulphate micelles an insertion in the micellar hydrophobic region conformationally similar to that found in sodium dodecylsulphate micelles occurs. In presence of mixed micelles the insertion and structuration occur in preferred regions when the membrane models are negatively charged. From the point of view of the mechanism of action, insertion its N terminus in negative regions of membrane led to hypothesize that this process would be similar to a binding to phosphatidylserine exposed like in apoptotic cells. Thymosin alpha1 when inserted may interact with nearby proteins and/or receptors acting as effector and causing a biological signaling cascade. The recent attention to the phosphatidylserine exposure in cells may enforce the interest for these findings. PMID- 26801938 TI - Naturally occurring amino acid derivatives with herbicidal, fungicidal or insecticidal activity. AB - Several naturally occurring amino acid derivatives display significant activities against weeds, fungi and insects: some of them have been even commercialized and are applied as crop protection agents. The 53 most important amino acid natural products with such efficacy are presented in this review together with their natural source, mode of action and biological activity. The diversity of the manifold bacterial, fungal and plantal sources of these compounds is impressive as well as their completely different structural scaffolds, ranging from cyclopeptides via unique non-proteinogenic amino acids to peptidyl nucleosides, the broad range of target enzymes from several different biochemical pathways, which they inhibit and also the plethora of different weeds, fungi and insects they are able to control. PMID- 26801939 TI - Survival outcomes of obese patients in type II endometrial cancer: Defining the prognostic impact of increasing BMI. AB - OBJECTIVE: To investigate the role of obesity as a risk factor for type II endometrial cancer (EC), as well as the prognostic significance of increasing body mass index (BMI) on survival. METHODS: A single institution retrospective analysis of 154 type II EC cases from 1987 to 2010 was conducted. Patients were categorized into cohorts by BMI (normal (<25), overweight (25-29.9), obese class I (30-34.9), and obese class II-III (>=35)). Descriptive, regression and ANOVA analyses were performed. Kaplan-Meier curves were compared with log rank tests. RESULTS: The BMI distribution was 22.8% normal BMI; 24% overweight; 17.5% class I; and 35.7% class II-III. The median follow up was 41 months. The median progression-free survival (PFS) was 45.4, 36.0, 35.3 and 42.0 months and overall survival (OS) was 54.7, 44.7, 44.8 and 49.7 months, among the respective groups. There was no association between BMI and PFS (p=0.71), OS (p=0.72), or time to recurrence (p=0.71). There were no differences among the increasing BMI groups compared to normal weight women for the risk of death. CONCLUSIONS: Our analysis did not reveal any differences in outcomes by BMI group. Our data reveals that obesity is highly prevalent in type II ECs, though obesity has not historically been described as a risk factor. While BMI as a single variable may not be prognostic for survival outcomes, the role of obesity as a risk factor for type II EC should be further investigated, given the increasing prevalence of obesity in type II ECs. PMID- 26801940 TI - Cytoreduction of diaphragmatic metastasis from ovarian cancer with involvement of the liver using a ventral liver mobilization technique. AB - OBJECTIVE: Upper abdominal spreading of advanced-stage ovarian cancer often involves the diaphragm. In addition, bulky diaphragmatic tumors occasionally infiltrate the liver. Here, we describe our early experiences with a ventral liver mobilization technique to remove diaphragmatic tumors with liver involvement. METHODS: Two patients with primary ovarian cancer and 1 patient with recurrent ovarian cancer underwent en bloc resections of a diaphragmatic tumor together with the full-thickness diaphragm and the liver tissue using a ventral liver mobilization technique. The surgical technique involved a full-thickness division of the diaphragm at the central tendon and a ventral mobilization of the right lobe of the liver, with entry into the pleural cavity. During the parenchymal transection of the liver, the posterior area of the right lobe of the liver was pressed using the surgeon's hand to reduce bleeding from the resection surface. After the completion of the en bloc resection, the diaphragmatic opening was closed using running sutures. RESULTS: All the diaphragmatic tumors were completely removed without severe bleeding in the current series. No intraoperative or postoperative complications occurred. CONCLUSION: Diaphragmatic tumors with involvement of the liver can be safely and effectively removed using a ventral liver mobilization technique. This surgical procedure may be suitable for the management of bulky diaphragmatic tumors in select patients. PMID- 26801941 TI - HE4, CA125 and risk of ovarian malignancy algorithm (ROMA) as diagnostic tools for ovarian cancer in patients with a pelvic mass: An Italian multicenter study. AB - OBJECTIVE: This multicenter study aims to evaluate HE4, CA125 and risk of ovarian malignancy algorithm (ROMA) performance in the differential diagnosis of epithelial ovarian cancer (EOC). METHODS: A total of 405 patients referred to gynecological oncologist with suspicious pelvic mass requiring a surgery for identification of EOC were consecutively enrolled; 387 patients satisfied inclusion criteria: 290 benign diseases; 15 borderline neoplasia and 82 tumors (73 EOC). RESULTS: Good diagnostic performance in discriminating benign from EOC patients was obtained for CA125, HE4 and ROMA when calculating optimal cut-off values: premenopause, specificity (SP) >86.6, sensitivity (SN) >82.6, area under the curves (AUC)>=0.894; postmenopause, SP>93.2, SN>82, AUC>=0.928. Fixing SP at 98%, performance indicators obtained for benign vs EOC patients were: premenopause, SN:65.2%, positive predictive value (+PV): 75%, positive likelihood ratio (+LR): 26.4 for CA125; SN:69.6%, +PV:76.2%, +LR:28.1 for HE4; SN:69.6%, +PV: 80%; +LR:35.1 for ROMA; postmenopause, SN:88%, +PV: 95.7%, +LR:38.7 for CA125; SN:78%, +PV:95.1%, +LR:34.3 for HE4; SN:88%, +PV:97.8%, +LR:77.4 for ROMA. When using routine cut-off thresholds, ROMA showed better well-balanced values of both SP and SN (premenopause, SN:87%, SP:86.1%; postmenopause, SN:90%; SP:94.3%). CONCLUSIONS: Overall, ROMA showed well balanced diagnostic performance to differentiate EOC from benign diseases. Meaningful differences of +PVs and +LRs between HE4 and CA125 suggest that the two markers may play at least in part different roles in EOC diagnosis, with HE4 seeming to be more efficient than CA125 in ruling in EOC patients in the disease group, also in early stages tumors, both in pre and postmenopause. PMID- 26801943 TI - Enantioselective Pharmacokinetics of Bambuterol in Preclinical Species: Does S bambuterol Influence the Clearance of the R-antipode? PMID- 26801945 TI - WEB as part of a multimodality treatment in complex, large, and partially thrombosed intracranial aneurysms: a single-center observational study of technical success, safety, and recurrence. AB - INTRODUCTION: Complex, large, wide-neck aneurysms, but particularly partially thrombosed intracranial aneurysms (PTIAs), have a greater tendency to recanalize after coil occlusion. The Woven Endovascular Bridge (WEB) combines shape memory wires braided to a relatively uniform, dense surface, which may limit its compaction and its incorporation into an existing aneurysm clot and may thus reduce PTIA recurrence. OBJECTIVE: To carry out a retrospective analysis of our experience with the WEB as part of a complex treatment in conjunction with other implants to assess the efficacy and safety of this technique. METHODS: Among 43 aneurysms treated with the WEB in our center, eight complex, large, wide-neck aneurysms were treated in conjunction with other implants (additional WEBs, coils, stents, flow diverters). Six of these eight aneurysms were PTIAs. All patients were followed up by DSA between 31/2 and 38 months. RESULTS: All eight (100%) of the complex, large, wide-neck aneurysms were treated successfully and without periprocedural adverse events (0%). At follow-up, the two non-thrombosed aneurysms were completely occluded, but all six PTIAs recurred (75%) and were re treated. There was no morbidity or mortality in these eight patients. CONCLUSIONS: Treatment of large, complex aneurysms with the WEB in conjunction with other implants was technically successful and safe but did not prevent recurrence of partially thrombosed aneurysms in our center. PTIA re-treatment was possible and not limited by the previously placed WEB. PMID- 26801944 TI - Management of sensitized pediatric patients prior to renal transplantation. AB - BACKGROUND: Data on renal allograft outcome in sensitized children are scarce. We report the clinical courses of four children who received desensitization therapy prior to renal transplantation in our institution. METHODS: Between 2009 and 2011, four pediatric patients with stage 5 chronic kidney disease received desensitization therapy due to: (1) positive donor-specific antibodies (DSA) and/or crossmatches with potential living donors, (2) more than three positive crossmatches with deceased donors or (3) high calculated panel-reactive antibody of >80 %. Desensitization with rituximab, intravenous immunoglobulin and bortezomib was performed in all patients. Induction therapy included combinations of plasmapheresis and/or alemtuzumab or anti-thymocyte globulin. Standard post transplant medications included tacrolimus, mycophenolate mofetil and prednisolone. RESULTS: Post-transplant screening revealed DSA in three patients. Biopsy showed no evidence of rejection at 1 month in two patients, one of whom developed chronic active antibody-mediated rejection 4.5 years later. One patient developed borderline acute cellular rejection at 1 month, but the serum creatinine level was stable and DSA disappeared without treatment 1 month later, with stable long-term allograft function at 3 years. Estimated or measured glomerular filtration rate of the patients ranged between 30 and 75 ml/min/1.73 m(2) after 1 to 4.5 years. CONCLUSIONS: The four sensitized patients reported here who received desensitization therapy had successful renal transplants with a low risk of immediate post-transplant rejection. Overall, long-term allograft functions and complications from immunosuppression were encouraging. PMID- 26801946 TI - Guidelines and parameters: percutaneous sclerotherapy for the treatment of head and neck venous and lymphatic malformations. PMID- 26801948 TI - Resuscitators who compared four simulated infant cardiopulmonary resuscitation methods favoured the three-to-one compression-to-ventilation ratio. AB - AIM: Suboptimal cardiopulmonary resuscitation (CPR) is associated with a poor outcome, and international guidelines state that resuscitators should optimise compression and ventilation techniques with as few interruptions as possible. We investigated compression and ventilation quality during simulated CPR with four compression-to-ventilation (C:V) methods. METHODS: In this crossover manikin study, 42 pairs of doctors, nurses, midwives and sixth-year medical students from two Norwegian hospitals provided two-minute resuscitation using the 3:1, 9:3 and 15:2 C:V methods and continuous chest compressions at 120 per minute with asynchronous ventilations (CCaV-120). We measured chest compression, ventilation mechanics and the resuscitators' preferences. RESULTS: C:V methods 3:1 and 9:3 provided comparable chest compressions and ventilation mechanics, whereas 15:2 produced fewer ventilations and lower minute volumes. The CCaV-120 method was significantly less effective than the 3:1 C:V ratio method: the chest compression depth was 1.9 mm lower, there were 25 fewer chest compressions and 21 fewer ventilations per minute, and the minute volume was 69 mL lower. The 3:1 C:V method also provided better coordination between resuscitators. CONCLUSION: Our comparison of four simulated infant cardiopulmonary resuscitation methods favoured the 3:1 C:V method, and the multidisciplinary group of participants felt it offered the best level of coordination between resuscitators. PMID- 26801947 TI - CT perfusion and angiographic assessment of pial collateral reperfusion in acute ischemic stroke: the CAPRI study. AB - BACKGROUND: The purpose of this study was to evaluate the correlation between a novel angiographic score for collaterals and CT perfusion (CTP) parameters in patients undergoing endovascular treatment for acute ischemic stroke (AIS). METHODS: 103 patients (mean age 66.7+/-12.7; 48.5% men) with AIS in the anterior circulation territory, imaged with non-contrast CT, CT angiography, and CTP, admitted within 8 h from symptom onset and treated with any endovascular approach, were retrospectively included in the study. Clinical, neuroradiological data, and all time intervals were collected. Careggi Collateral Score (CCS) was used for angiographic assessment of collaterals and the Alberta Stroke Program Early CT Score (ASPECTS) for semiquantitative analysis of CTP maps. Two centralized core laboratories separately reviewed angiographic data, whereas CT findings were evaluated by an expert neuroradiologist. Univariate and multivariate analysis were performed considering CCS both as an ordinal and a dichotomous variable. RESULTS: 37/103 patients (35.9%) received intravenous tissue plasminogen activator. Median (IQR) ASPECTS was 9 (6-10) for admission CT, 9 (5-10) for cerebral blood volume (CBV) maps, 3 (2-3) for mean transit time maps, 3 (2-4), for cerebral blood flow maps, and 5 (3-7) for CTP mismatch. Univariate analysis showed a significant correlation between CCS and ASPECTS for all CTP parameters. Multivariate analysis confirmed an independent association only between CCS and CBV (p=0.020 when CCS was considered as a dichotomous variable, p=0.026 with ordinal CCS). CONCLUSIONS: A correlation between angiographic assessment of the collateral circulation and CTP seems to be present, suggesting that CCS may provide an indirect evaluation of the infarct core volume to consider for patient selection in AIS. PMID- 26801949 TI - An unusual cause of plantar pustulosis. PMID- 26801950 TI - Drinking During Pregnancy and the Developing Brain: Is Any Amount Safe? AB - Heavy prenatal alcohol exposure can have lifelong, disabling effects on brain and cognition. Unlike animal studies, research on light-to-moderate drinking in humans demonstrates less consistent impact. Discussions of negative research findings in popular media underestimate potential adverse outcomes and complicate decisions about risks versus benefits of light-to-moderate drinking during pregnancy. PMID- 26801951 TI - Hemangiopericytoma arising from the cartilage of the external auditory canal. AB - BACKGROUND: Hemangiopericytomas (HPCs) are soft tissue tumors with histological variability and unpredictable clinical and biological behavior. HPCs in the head and neck are uncommon, the growth pattern is nonspecific; thus, diagnosis is often made by exclusion. METHODS: A 43-year-old man complained of a short history of right ear pain associated with a growing mass in the right external auditory canal. Subsequent hearing loss in the right ear brought the patient to undergo a CT scan and an MRI. The relevant literature was also reviewed. RESULTS: The imaging revealed a neoplasm arising from the floor of the right external auditory canal. The neoplasm was removed with the diagnosis of HPC. CONCLUSION: The literature reports few cases of HPC of the external auditory canal. Their rarity in this area leads to difficulties in diagnosis. Morphology is not predictive of their behavior, so close follow-up is mandatory for their correct management. PMID- 26801952 TI - Impact of using different blood donor subpopulations and models on the estimation of transfusion transmission residual risk of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus in Zimbabwe. AB - BACKGROUND: Various models for estimating the residual risk (RR) of transmission of infections by blood transfusion have been published mainly based on data from high-income countries. However, to obtain the data required for such an assessment remains challenging for most developing settings. The National Blood Service Zimbabwe (NBSZ) adapted a published incidence-window period (IWP) model, which has less demanding data requirements. In this study we assess the impact of various definitions of blood donor subpopulations and models on RR estimates. We compared the outcomes of two published models and an adapted NBSZ model. STUDY DESIGN AND METHODS: The Schreiber IWP model (Model 1), an amended version (Model 2), and an adapted NBSZ model (Model 3) were applied. Variably the three models include prevalence, incidence, preseroconversion intervals, mean lifetime risk, and person-years at risk. Annual mean RR estimates and 95% confidence intervals for each of the three models for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) were determined using NBSZ blood donor data from 2002 through 2011. RESULTS: The annual mean RR estimates for Models 1 through 3 were 1 in 6542, 5805, and 6418, respectively for HIV; 1 in 1978, 2027, and 1628 for HBV; and 1 in 9588, 15,126, and 7750, for HCV. CONCLUSIONS: The adapted NBSZ model provided comparable results to the published methods and these highlight the high occurrence of HBV in Zimbabwe. The adapted NBSZ model could be used as an alternative to estimate RRs when in settings where two repeat donations are not available. PMID- 26801953 TI - Hypoglycemic Syndrome without Hyperinsulinemia. A Diagnostic Challenge. AB - The most common cause of organic fasting hypoglycemia in adults is the presence of an insulin-producing pancreatic adenoma, but when high insulin levels are not found, the differential diagnosis is challenging. Misdiagnosis can lead to an unnecessary pancreatectomy. Insulin concentrations may be low in some cases despite a clinical history suggestive of insulinoma. In these cases, a proinsulinoma should be suspected, although the rarity of this condition requires an extensive workup before reaching a final diagnosis. We describe an unusual case of a 38-year-old man with a severe hypoglycemic syndrome due to a proinsulin secreting pancreatic adenoma. Insulin was measured by the specific assay and suppressed under the lower detection limit during fasting hypoglycemia. Serum proinsulin and C-peptide levels were abnormally elevated, and further tests revealed an islet cell tumor. The tumor was surgically removed, relieving the fasting hypoglycemia. Histopathological study showed a conventional well differentiated neuroendocrine tumor with high immunoreactivity against proinsulin and with lesser intensity against insulin. Interestingly, GS-9A8 antibody clone used for immunostaining proinsulin did not cross-react with human insulin or C peptide, providing an unbiased picture of proinsulin secretion. The resolution of symptoms, the fall of proinsulin concentrations after tumor removal and the histopathology study confirmed the diagnosis of proinsulinoma. PMID- 26801954 TI - Prognostic significance of infections in critically ill adult patients with acute liver injury: a retrospective cohort study. AB - BACKGROUND AND AIMS: Patients with acute liver failure have high rates of infections, likely from defects in immune function. Whether infections are independently associated with poor outcomes is unclear. We hypothesized that patients with acute liver injury who developed infections were at increased risk of adverse outcomes. METHODS: We conducted a retrospective analysis of 150 critically ill adult patients admitted with acute liver dysfunction at a single academic institution between 2005 and 2011. We excluded patients with immunocompromised states, patients with chronic liver disease and patients who died or were discharged within 48 h of admission. Our primary endpoint was a 30 day event-free survival, with events defined as either death or liver transplantation. Our secondary endpoint was length of stay. Univariate and multivariate analyses were performed to determine associations between presence of infection and our primary and secondary endpoints. RESULTS: Of our cohort of 150 patients, 62 (41%) were infected and 88 (59%) were not infected. Of the infected patients, 45% died or underwent transplantation, compared to 22% for the non-infected patients (P = 0.003). Univariate and multivariate analyses demonstrated that infections in patients with acute liver dysfunction were an independent predictor of poor outcome (i.e. death or transplantation). In addition, specific types of infection, including pneumonia, independently led to a 48% increase in length of stay (P = 0.002). CONCLUSIONS: Infections in patients with acute liver dysfunction are associated with increased risk of death or transplant and increased hospital length of stay. PMID- 26801955 TI - The superficial white matter in Alzheimer's disease. AB - White matter abnormalities have been shown in the large deep fibers of Alzheimer's disease patients. However, the late myelinating superficial white matter comprised of intracortical myelin and short-range association fibers has not received much attention. To investigate this area, we extracted a surface corresponding to the superficial white matter beneath the cortex and then applied a cortical pattern-matching approach which allowed us to register and subsequently sample diffusivity along thousands of points at the interface between the gray matter and white matter in 44 patients with Alzheimer's disease (Age: 71.02 +/- 5.84, 16M/28F) and 47 healthy controls (Age 69.23 +/- 4.45, 19M/28F). In patients we found an overall increase in the axial and radial diffusivity across most of the superficial white matter (P < 0.001) with increases in diffusivity of more than 20% in the bilateral parahippocampal regions and the temporal and frontal lobes. Furthermore, diffusivity correlated with the cognitive deficits measured by the Mini-Mental State Examination scores (P < 0.001). The superficial white matter has a unique microstructure and is critical for the integration of multimodal information during brain maturation and aging. Here we show that there are major abnormalities in patients and the deterioration of these fibers relates to clinical symptoms in Alzheimer's disease. PMID- 26801956 TI - Social power, conflict policing, and the role of subordination signals in rhesus macaque society. AB - OBJECTIVES: Policing is a conflict-limiting mechanism observed in many primate species. It is thought to require a skewed distribution of social power for some individuals to have sufficiently high social power to stop others' fights, yet social power has not been examined in most species with policing behavior. We examined networks of subordination signals as a source of social power that permits policing behavior in rhesus macaques. MATERIALS AND METHODS: For each of seven captive groups of rhesus macaques, we (a) examined the structure of subordination signal networks and used GLMs to examine the relationship between (b) pairwise dominance certainty and subordination network pathways and (c) policing frequency and social power (group-level convergence in subordination signaling pathways). RESULTS: Networks of subordination signals had perfect linear transitivity, and pairs connected by both direct and indirect pathways of signals had more certain dominance relationships than pairs with no such network connection. Social power calculated using both direct and indirect network pathways showed a heavy-tailed distribution and positively predicted conflict policing. CONCLUSIONS: Our results empirically substantiate that subordination signaling is associated with greater dominance relationship certainty and further show that pairs who signal rarely (or not at all) may use information from others' signaling interactions to infer or reaffirm the relative certainty of their own relationships. We argue that the network of formal dominance relationships is central to societal stability because it is important for relationship stability and also supports the additional stabilizing mechanism of policing. PMID- 26801957 TI - ELASPIC web-server: proteome-wide structure-based prediction of mutation effects on protein stability and binding affinity. AB - ELASPIC is a novel ensemble machine-learning approach that predicts the effects of mutations on protein folding and protein-protein interactions. Here, we present the ELASPIC webserver, which makes the ELASPIC pipeline available through a fast and intuitive interface. The webserver can be used to evaluate the effect of mutations on any protein in the Uniprot database, and allows all predicted results, including modeled wild-type and mutated structures, to be managed and viewed online and downloaded if needed. It is backed by a database which contains improved structural domain definitions, and a list of curated domain-domain interactions for all known proteins, as well as homology models of domains and domain-domain interactions for the human proteome. Homology models for proteins of other organisms are calculated on the fly, and mutations are evaluated within minutes once the homology model is available. AVAILABILITY AND IMPLEMENTATION: The ELASPIC webserver is available online at http://elaspic.kimlab.org CONTACT: pm.kim@utoronto.ca or pi@kimlab.orgSupplementary data: Supplementary data are available at Bioinformatics online. PMID- 26801958 TI - MS-REDUCE: an ultrafast technique for reduction of big mass spectrometry data for high-throughput processing. AB - MOTIVATION: Modern proteomics studies utilize high-throughput mass spectrometers which can produce data at an astonishing rate. These big mass spectrometry (MS) datasets can easily reach peta-scale level creating storage and analytic problems for large-scale systems biology studies. Each spectrum consists of thousands of peaks which have to be processed to deduce the peptide. However, only a small percentage of peaks in a spectrum are useful for peptide deduction as most of the peaks are either noise or not useful for a given spectrum. This redundant processing of non-useful peaks is a bottleneck for streaming high-throughput processing of big MS data. One way to reduce the amount of computation required in a high-throughput environment is to eliminate non-useful peaks. Existing noise removing algorithms are limited in their data-reduction capability and are compute intensive making them unsuitable for big data and high-throughput environments. In this paper we introduce a novel low-complexity technique based on classification, quantization and sampling of MS peaks. RESULTS: We present a novel data-reductive strategy for analysis of Big MS data. Our algorithm, called MS-REDUCE, is capable of eliminating noisy peaks as well as peaks that do not contribute to peptide deduction before any peptide deduction is attempted. Our experiments have shown up to 100* speed up over existing state of the art noise elimination algorithms while maintaining comparable high quality matches. Using our approach we were able to process a million spectra in just under an hour on a moderate server. AVAILABILITY AND IMPLEMENTATION: The developed tool and strategy has been made available to wider proteomics and parallel computing community and the code can be found at https://github.com/pcdslab/MSREDUCE CONTACT: : fahad.saeed@wmich.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26801959 TI - Multi-task consensus clustering of genome-wide transcriptomes from related biological conditions. AB - MOTIVATION: Identifying the shared and pathogen-specific components of host transcriptional regulatory programs is important for understanding the principles of regulation of immune response. Recent efforts in systems biology studies of infectious diseases have resulted in a large collection of datasets measuring host transcriptional response to various pathogens. Computational methods to identify and compare gene expression modules across different infections offer a powerful way to identify strain-specific and shared components of the regulatory program. An important challenge is to identify statistically robust gene expression modules as well as to reliably detect genes that change their module memberships between infections. RESULTS: We present MULCCH (MULti-task spectral Consensus Clustering for Hierarchically related tasks), a consensus extension of a multi-task clustering algorithm to infer high-confidence strain-specific host response modules under infections from multiple virus strains. On simulated data, MULCCH more accurately identifies genes exhibiting pathogen-specific patterns compared to non-consensus and nonmulti-task clustering approaches. Application of MULCCH to mammalian transcriptional response to a panel of influenza viruses showed that our method identifies clusters with greater coherence compared to non consensus methods. Further, MULCCH derived clusters are enriched for several immune system-related processes and regulators. In summary, MULCCH provides a reliable module-based approach to identify molecular pathways and gene sets characterizing commonality and specificity of host response to viruses of different pathogenicities. AVAILABILITY AND IMPLEMENTATION: The source code is available at https://bitbucket.org/roygroup/mulcch CONTACT: sroy@biostat.wisc.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26801961 TI - The neonate versus adult mammalian immune system in cardiac repair and regeneration. AB - The immune system is a crucial player in tissue homeostasis and wound healing. A sophisticated cascade of events triggered upon injury ensures protection from infection and initiates and orchestrates healing. While the neonatal mammal can readily regenerate damaged tissues, adult regenerative capacity is limited to specific tissue types, and in organs such as the heart, adult wound healing results in fibrotic repair and loss of function. Growing evidence suggests that the immune system greatly influences the balance between regeneration and fibrotic repair. The neonate mammalian immune system has impaired pro inflammatory function, is prone to T-helper type 2 responses and has an immature adaptive immune system skewed towards regulatory T cells. While these characteristics make infants susceptible to infection and prone to allergies, it may also provide an immunological environment permissive of regeneration. In this review we will give a comprehensive overview of the immune cells involved in healing and regeneration of the heart and explore differences between the adult and neonate immune system that may explain differences in regenerative ability. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID- 26801960 TI - Structured sparse canonical correlation analysis for brain imaging genetics: an improved GraphNet method. AB - MOTIVATION: Structured sparse canonical correlation analysis (SCCA) models have been used to identify imaging genetic associations. These models either use group lasso or graph-guided fused lasso to conduct feature selection and feature grouping simultaneously. The group lasso based methods require prior knowledge to define the groups, which limits the capability when prior knowledge is incomplete or unavailable. The graph-guided methods overcome this drawback by using the sample correlation to define the constraint. However, they are sensitive to the sign of the sample correlation, which could introduce undesirable bias if the sign is wrongly estimated. RESULTS: We introduce a novel SCCA model with a new penalty, and develop an efficient optimization algorithm. Our method has a strong upper bound for the grouping effect for both positively and negatively correlated features. We show that our method performs better than or equally to three competing SCCA models on both synthetic and real data. In particular, our method identifies stronger canonical correlations and better canonical loading patterns, showing its promise for revealing interesting imaging genetic associations. AVAILABILITY AND IMPLEMENTATION: The Matlab code and sample data are freely available at http://www.iu.edu/~shenlab/tools/angscca/ CONTACT: shenli@iu.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26801962 TI - Antifungal mechanisms of a plant defensin MtDef4 are not conserved between the ascomycete fungi Neurospora crassa and Fusarium graminearum. AB - Defensins play an important role in plant defense against fungal pathogens. The plant defensin, MtDef4, inhibits growth of the ascomycete fungi, Neurospora crassa and Fusarium graminearum, at micromolar concentrations. We have reported that MtDef4 is transported into the cytoplasm of these fungi and exerts its antifungal activity on intracellular targets. Here, we have investigated whether the antifungal mechanisms of MtDef4 are conserved in these fungi. We show that N. crassa and F. graminearum respond differently to MtDef4 challenge. Membrane permeabilization is required for the antifungal activity of MtDef4 against F. graminearum but not against N. crassa. We find that MtDef4 is targeted to different subcellular compartments in each fungus. Internalization of MtDef4 in N. crassa is energy-dependent and involves endocytosis. By contrast, MtDef4 appears to translocate into F. graminearum autonomously using a partially energy dependent pathway. MtDef4 has been shown to bind to the phospholipid phosphatidic acid (PA). We provide evidence that the plasma membrane localized phospholipase D, involved in the biosynthesis of PA, is needed for entry of this defensin in N. crassa, but not in F. graminearum. To our knowledge, this is the first example of a defensin which inhibits the growth of two ascomycete fungi via different mechanisms. PMID- 26801963 TI - Chromatographic fractionation and molecular mass characterization of Cercidium praecox (Brea) gum. AB - BACKGROUND: Brea gum (BG) is an exudate from the Cercidium praecox tree that grows in semi-arid regions of Argentina. Some previous studies on BG have shown physicochemical characteristics and functional features similar to those of gum arabic. However, there is a need to elucidate the molecular structure of BG to understand the functionality. In this sense, BG was fractionated using hydrophobic interaction chromatography and the obtained fractions were analyzed by size exclusion chromatography. RESULTS: Analysis of the fractions showed that the bulk of the gum (approx. 84% of the polysaccharides) was a polysaccharide of 2.79 * 10(3) kDa. The second major fraction (approx. 16% of the polysaccharides) was a polysaccharide-protein complex with a molecular mass of 1.92 * 10(5) kDa. A third fraction consisted of protein species with a wide range of molecular weights. The molecular weight distribution of the protein fraction was analyzed by size exclusion chromatography. Comparison of the elution profiles of the exudates in native and reducing conditions revealed that some of the proteins were forming aggregates through disulfide bridges in native conditions. Further analysis of the protein fraction by SDS-PAGE showed proteins with molecular weight ranging from 6.5 to 66 kDa. CONCLUSIONS: The findings showed that BG consists of several fractions with heterogeneous chemical composition and polydisperse molecular weight distributions. (c) 2016 Society of Chemical Industry. PMID- 26801964 TI - The influence of reduced light intensity on the response of benthic diatoms to herbicide exposure. AB - Herbicide pollution events in aquatic ecosystems often coincide with increased turbidity and reduced light intensity. It is therefore important to determine whether reduced light intensity can influence herbicide toxicity, especially to primary producers such as benthic diatoms. Benthic diatoms collected from 4 rivers were exposed to herbicides in 48 h rapid toxicity tests under high light (100 umol m(-2) s(-1) ) and low light (20 umol m(-2) s(-1) ) intensities. The effects of 2 herbicides (atrazine and glyphosate) were assessed on 26 freshwater benthic diatom taxa. There was no significant interaction of light and herbicide effects at the community level or on the majority (22 of 26) of benthic diatom taxa. This indicates that low light levels will likely have only a minor influence on the response of benthic diatoms to herbicides. Environ Toxicol Chem 2016;35:2252-2260. (c) 2016 SETAC. PMID- 26801965 TI - A highly recombined, high-density, eight-founder wheat MAGIC map reveals extensive segregation distortion and genomic locations of introgression segments. AB - Multiparent Advanced Generation Intercross (MAGIC) mapping populations offer unique opportunities and challenges for marker and QTL mapping in crop species. We have constructed the first eight-parent MAGIC genetic map for wheat, comprising 18 601 SNP markers. We validated the accuracy of our map against the wheat genome sequence and found an improvement in accuracy compared to published genetic maps. Our map shows a notable increase in precision resulting from the three generations of intercrossing required to create the population. This is most pronounced in the pericentromeric regions of the chromosomes. Sixteen percent of mapped markers exhibited segregation distortion (SD) with many occurring in long (>20 cM) blocks. Some of the longest and most distorted blocks were collinear with noncentromeric high-marker-density regions of the genome, suggesting they were candidates for introgression fragments introduced into the bread wheat gene pool from other grass species. We investigated two of these linkage blocks in detail and found strong evidence that one on chromosome 4AL, showing SD against the founder Robigus, is an interspecific introgression fragment. The completed map is available from http://www.niab.com/pages/id/326/Resources. PMID- 26801966 TI - Selective localization of myosin-I proteins in macropinosomes and actin waves. AB - Class I myosins are widely expressed with roles in endocytosis and cell migration in a variety of cell types. Dictyostelium express multiple myosin Is, including three short-tailed (Myo1A, Myo1E, Myo1F) and three long-tailed (Myo1B, Myo1C, Myo1D). Here we report the molecular basis of the specific localizations of short tailed Myo1A, Myo1E, and Myo1F compared to our previously determined localization of long-tailed Myo1B. Myo1A and Myo1B have common and unique localizations consistent with the various features of their tail region; specifically the BH sites in their tails are required for their association with the plasma membrane and heads are sufficient for relocalization to the front of polarized cells. Myo1A does not localize to actin waves and macropinocytic protrusions, in agreement with the absence of a tail region which is required for these localizations of Myo1B. However, in spite of the overall similarity of their domain structures, the cellular distributions of Myo1E and Myo1F are quite different from Myo1A. Myo1E and Myo1F, but not Myo1A, are associated with macropinocytic cups and actin waves. The localizations of Myo1E and Myo1F in macropinocytic structures and actin waves differ from the localization of Myo1B. Myo1B colocalizes with F-actin in the actin waves and at the tips of mature macropinocytic cups whereas Myo1E and Myo1F are in the interior of actin waves and along the entire surface of macropinocytic cups. Our results point to different mechanisms of targeting of short- and long-tailed myosin Is, and are consistent with these myosins having both shared and divergent cellular functions. PMID- 26801967 TI - CTLA4Fcepsilon, a novel soluble fusion protein that binds B7 molecules and the IgE receptors, and reduces human in vitro soluble CD23 production and lymphocyte proliferation. AB - Immunoglobulin E-mediated allergy and certain autoimmune diseases are characterized by the presence of a T helper type 2 (Th2) immune response and allergen-specific or self-reactive IgE. Soluble CD23 (sCD23) is a B-cell factor that fosters IgE class-switching and synthesis, suggesting that sCD23 may be a therapeutic target for these pathologies. We produced a recombinant protein, CTLA4Fcepsilon, by fusing the ectodomain of the immunoregulatory molecule cytotoxic T-lymphocyte antigen 4 (CTLA-4) with a fragment of the IgE H-chain constant region. In SDS-PAGE/inmunoblot analyses, CTLA4Fcepsilon appeared as a 70,000 MW polypeptide that forms homodimers. Flow cytometry showed that CTLA4Fcepsilon binds to IgE receptors FcepsilonRI and FcepsilonRII/CD23, as well as to CTLA-4 counter-receptors CD80 and CD86. Binding of CTLA4Fcepsilon to FcepsilonRII/CD23 appeared stronger than that of IgE. Since the cells used to study CD23 binding express CD80 and CD86, simultaneous binding of CTLA4Fcepsilon to CD23 and CD80/CD86 seems to occur and would explain this difference. As measured by a human CD23-specific ELISA, CTLA4Fcepsilon - but not IgE - induced a concentration-dependent reduction of sCD23 in culture supernatants of RPMI-8866 cells. Our results suggest that the simultaneous binding of CTLA4FcE to CD23 CD80/CD86 may cause the formation of multi-molecular complexes that are either internalized or pose a steric hindrance to enzymatic proteolysis, so blocking sCD23 generation. CTLA4Fcepsilon caused a concentration-dependent reduction of lymphocyte proliferation in human peripheral blood mononuclear cell samples stimulated in vitro with concanavalin A. The ability to bind IgE receptors on effector cells, to regulate the production of sCD23 and to inhibit lymphocyte proliferation suggests that CTLA4FcE has immunomodulatory properties on human Th2 responses. PMID- 26801968 TI - Cognitive Control as a Moderator of Temperamental Motivations Toward Adolescent Risk-Taking Behavior. AB - Few studies have directly examined whether cognitive control can moderate the influence of temperamental positive and negative affective traits on adolescent risk-taking behavior. Using a combined multimethod, latent variable approach to the assessment of adolescent risk-taking behavior and cognitive control, this study examined whether cognitive control moderates the influence of temperamental surgency and frustration on risk-taking behavior in a sample of 177 adolescents (Mage = 16.12 years, SD = 0.69). As predicted, there was a significant interaction between cognitive control and frustration, but not between cognitive control and surgency, in predicting risk-taking behavior. These findings have important implications and suggest that the determinants of adolescent risk taking depend on the valence of the affective motivation for risk-taking behavior. PMID- 26801969 TI - Effect of dehydration on the development of collaterals in acute middle cerebral artery occlusion. AB - BACKGROUND AND PURPOSE: Recent large series studies have demonstrated that dehydration is common amongst stroke subjects and is associated with poor outcome. However, the effects of hydration status on the development of collaterals have never been discussed. In this study, the hypothesis that hydration status is an important factor for developing collaterals after acute middle cerebral artery (MCA) infarction was tested. METHODS: Eighty-seven patients with acute infarction due to occlusion of the MCA were enrolled. Two collateral markers, posterior cerebral artery (PCA) laterality and fluid attenuated inversion recovery hyperintense vessels (HVs) were assessed from magnetic resonance imaging. Dehydration status was defined by a nitrogen to creatinine ratio ? of 15. The associations between dehydration status and the development of collaterals were estimated. RESULTS: Sixty-one of 87 patients (70.1%) were identified as dehydrated. The development of PCA laterality and HVs shows a significant difference between dehydrated and euhydrated patients. A serum nitrogen to creatinine ratio <15, diastolic blood pressure and the presence of a dense MCA on computed tomography were significantly associated with the development of PCA laterality. A serum nitrogen to creatinine ratio <15, the initial National Institutes of Health Stroke Scale score, the presence of a dense MCA and calcifications of the internal carotid artery on computed tomography were significantly associated with the development of HVs. Dehydration remained an independent negative predictor for the development of PCA laterality and HVs in the multivariate analysis. CONCLUSIONS: Hydration status is associated with the development of collateral flow after acute MCA occlusion. This preliminary study provides an imaging clue that hydration status and early hydration therapy could be important for acute stroke management. PMID- 26801970 TI - Long term effect of early intervention service on duration of untreated psychosis in youth and adult population in Hong Kong. AB - AIM: The current study explored the effect of an early intervention (EI) service for psychosis in Hong Kong (EASY) on the reduction of the duration of untreated psychosis (DUP) at 10 years, in adolescent and adult patients. METHOD: Data from three first-episode psychosis (FEP) studies conducted over 10 years using the same DUP assessment was analysed. FEP study 1 year before the EI service (2000) was used as a control, with those aged <25 comprising the youth psychosis control group and those aged over 25 comprising the adult psychosis control group. Data from the EASY service collected in 2010 constituted the youth psychosis EI group and data from an adult EI service collected from 2009 to 2011 constituted the adult psychosis EI group. DUP of EI and control groups was compared. The effect of the mode of onset and family history of psychosis on DUP was studied. RESULTS: DUP in the adult group was significantly reduced from median of 180 days to 93 days after 10 years (U = 12 906.50, P = 0.01), particularly in those with gradual onset and without family history. However, no significant change of DUP was found in the youth psychosis group. CONCLUSIONS: Results of the current study provide evidence that EI programmes with public awareness campaign can significantly reduce DUP of adult patients but not in youth group. The effect is more specific in those with long DUP. Further research should explore the specific factors contributed to the long DUP of patients of different age groups so as to establish targeted intervention strategies. PMID- 26801972 TI - Fine mapping of a salmonid E2 alphavirus neutralizing epitope. AB - In this study, we aimed to characterize the epitope recognized by the neutralizing 17H23 mAb directed against the E2 glycoprotein of most of salmonid alphavirus (SAV) subtypes and widely used in several laboratories to routinely diagnose SAV. We hypothesized that the 17H23 epitope was located in the major domain B, previously identified in the E2 of mammalian alphaviruses as the domain recognized by most of the E2 neutralizing mAbs. Indeed, the SAV E2 domain B counterpart is contained in the protein domain previously characterized as being recognized by mAb 17H23. Thus, to precisely characterize the 17H23 epitope, we developed an alanine scanning mutagenesis approach coupled with the generation of the respective recombinant SAV (rSAV) by using the available infectious cDNA. Ten mutant rSAVs termed A-J from E2 aa 223-236 were produced and characterized in vitro using indirect immunofluorescence assays on virus-infected cells with mAbs 17H23, 51B8 (another non-neutralizing anti-E2 mAb) and 19F3 directed against the non-structural protein nsp1. Two of the mutant rSAVs (G and H) escaped neutralization by mAb 17H23. In addition, we showed that when juvenile trout were infected by bath immersion with the rSAV mutants, some of them were either totally (D, E and G) or partially (H) attenuated. Together, the data from the in vitro and in vivo experiments indicated that the putative 17H23 amino acid sequence epitope comprised the short amino acid sequence (227)FTSDS(231). PMID- 26801971 TI - Joint-linkage mapping and GWAS reveal extensive genetic loci that regulate male inflorescence size in maize. AB - Both insufficient and excessive male inflorescence size leads to a reduction in maize yield. Knowledge of the genetic architecture of male inflorescence is essential to achieve the optimum inflorescence size for maize breeding. In this study, we used approximately eight thousand inbreds, including both linkage populations and association populations, to dissect the genetic architecture of male inflorescence. The linkage populations include 25 families developed in the U.S. and 11 families developed in China. Each family contains approximately 200 recombinant inbred lines (RILs). The association populations include approximately 1000 diverse lines from the U.S. and China. All inbreds were genotyped by either sequencing or microarray. Inflorescence size was measured as the tassel primary branch number (TBN) and tassel length (TL). A total of 125 quantitative trait loci (QTLs) were identified (63 for TBN, 62 for TL) through linkage analyses. In addition, 965 quantitative trait nucleotides (QTNs) were identified through genomewide study (GWAS) at a bootstrap posterior probability (BPP) above a 5% threshold. These QTLs/QTNs include 24 known genes that were cloned using mutants, for example Ramosa3 (ra3), Thick tassel dwarf1 (td1), tasselseed2 (ts2), liguleless2 (lg2), ramosa1 (ra1), barren stalk1 (ba1), branch silkless1 (bd1) and tasselseed6 (ts6). The newly identified genes encode a zinc transporter (e.g. GRMZM5G838098 and GRMZM2G047762), the adapt in terminal region protein (e.g. GRMZM5G885628), O-methyl-transferase (e.g. GRMZM2G147491), helix loop-helix (HLH) DNA-binding proteins (e.g. GRMZM2G414252 and GRMZM2G042895) and an SBP-box protein (e.g. GRMZM2G058588). These results provide extensive genetic information to dissect the genetic architecture of inflorescence size for the improvement of maize yield. PMID- 26801973 TI - Hepatoprotective effect of licorice, the root of Glycyrrhiza uralensis Fischer, in alcohol-induced fatty liver disease. AB - BACKGROUND: Our previous study suggested that licorice has anti-inflammatory activity in lipopolysaccharide-stimulated microglial cells and anti-oxidative activity in tert-butyl hydroperoxide-induced oxidative liver damage. In this study, we evaluated the effect of licorice on chronic alcohol-induced fatty liver injury mediated by inflammation and oxidative stress. METHODS: Raw licorice was extracted, and quantitative and qualitative analysis of its components was performed by using LC-MS/MS. Mice were fed a liquid alcohol diet with or without licorice for 4 weeks. RESULTS: We have standardized 70% fermented ethanol extracted licorice and confirmed by LC-MS/MS as glycyrrhizic acid (GA), 15.77 +/- 0.34 MUg/mg; liquiritin (LQ), 14.55 +/- 0.42 MUg/mg; and liquiritigenin (LG), 1.34 +/- 0.02 MUg/mg, respectively. Alcohol consumption increased serum alanine aminotransferase and aspartate aminotransferase activities and the levels of triglycerides and tumor necrosis factor (TNF)-alpha. Lipid accumulation in the liver was also markedly induced, whereas the glutathione level was reduced. All these alcohol-induced changes were effectively inhibited by licorice treatment. In particular, the hepatic glutathione level was restored and alcohol-induced TNF alpha production was significantly inhibited by licorice. CONCLUSION: Taken together, our data suggests that protective effect of licorice against alcohol induced liver injury may be attributed to its anti-inflammatory activity and enhancement of antioxidant defense. PMID- 26801974 TI - A meta-analysis of the impacts of internal migration on child health outcomes in China. AB - BACKGROUND: According to China's 2010 population census, 38.81 million children migrated from rural to urban areas in Mainland China, a phenomenon that has attracted much scholarly attention. Due to the lack of quantitative synthesis of migrant children's developmental outcomes, we undertook a meta-analysis to compare their developmental outcomes with those of their urban counterparts. METHODS: We searched Applied Social Sciences Index and Abstracts (ASSIA), Australian Education Index, British Education Index, ERIC, ProQuest Education Journals, PsycINFO, Social Services Abstracts, Family & Society Studies Worldwide, Medline, Women's Studies International databases and the Chinese CNKI database to identify relevant studies. Studies reporting physical and mental health outcomes of migrant children as well as potential protective and risk factors of child developmental outcomes were included. We assessed study quality using a quality assessment checklist. RESULTS: We selected 25 studies from a total of 1592. Our results reveal that migrant children in public schools present significantly greater mental health problems and lower well-being than their urban counterparts, while migrant children in migrant schools do not present significantly different outcomes. In addition, migrant children were found to be more likely to be exposed to physical health risks due to limited utilization of health services. The disadvantageous health outcomes of migrant children were found to be related to a series of individual and social factors, including academic performance, social relationships, and discrimination. CONCLUSIONS: Migrant children are disadvantaged by the sociocultural circumstances in urban areas. Government should target them and provide appropriate support in order to improve their developmental status, which will have a positive impact on the stability and development of society. PMID- 26801975 TI - Ebola vaccine will be made available for emergency use. PMID- 26801976 TI - Aberrant Notch Signaling in the Bone Marrow Microenvironment of Acute Lymphoid Leukemia Suppresses Osteoblast-Mediated Support of Hematopoietic Niche Function. AB - More than half of T-cell acute lymphoblastic leukemia (T-ALL) patients harbor gain-of-function mutations in the intracellular domain of Notch1. Diffuse infiltration of the bone marrow commonly occurs in T-ALL and relapsed B-cell acute lymphoblastic leukemia patients, and is associated with worse prognosis. However, the mechanism of leukemia outgrowth in the marrow and the resulting biologic impact on hematopoiesis are poorly understood. Here, we investigated targetable cellular and molecular abnormalities in leukemia marrow stroma responsible for the suppression of normal hematopoiesis using a T-ALL mouse model and human T-ALL xenografts. We found that actively proliferating leukemia cells inhibited normal hematopoietic stem and progenitor cell (HSPC) proliferation and homing to the perivascular region. In addition, leukemia development was accompanied by the suppression of the endosteum-lining osteoblast population. We further demonstrated that aberrant Notch activation in the stroma plays an important role in negatively regulating the expression of CXLC12 on osteoblasts and their differentiation. Notch blockade reversed attenuated HSPC cycling, leukemia-associated abnormal blood lineage distribution, and thrombocytopenia as well as recovered osteoblast and HSPC abundance and improved the hematopoietic supportive functions of osteoblasts. Finally, we confirmed that reduced osteoblast frequency and enhanced Notch signaling were also features of the marrow stroma of human ALL tissues. Collectively, our findings suggest that therapeutically targeting the leukemia-infiltrated hematopoietic niche may restore HSPC homeostasis and improve the outcome of ALL patients. PMID- 26801978 TI - Erratum to: Feasibility of focal cerebral ischemia and reperfusion surgery combined with chronic unpredictable mild stress to simulate the post-stroke depressive state in rats. AB - Erratum to: Behav Brain Funct (2015) 11:39, DOI 10.1186/s12993-015-0085-5. Unfortunately the original version of this article contained an error. After publication it was brought to our attention that one of the authors' names was incorrectly spelt. The original spelling reads as "LiXinhao Jin", however the correct spelling should be Xinhao Jin. This has now been updated on the website. PMID- 26801977 TI - Notch4 Signaling Induces a Mesenchymal-Epithelial-like Transition in Melanoma Cells to Suppress Malignant Behaviors. AB - The effects of Notch signaling are context-dependent and both oncogenic and tumor suppressive functions have been described. Notch signaling in melanoma is considered oncogenic, but clinical trials testing Notch inhibition in this malignancy have not proved successful. Here, we report that expression of the constitutively active intracellular domain of Notch4 (N4ICD) in melanoma cells triggered a switch from a mesenchymal-like parental phenotype to an epithelial like phenotype. The epithelial-like morphology was accompanied by strongly reduced invasive, migratory, and proliferative properties concomitant with the downregulation of epithelial-mesenchymal transition markers Snail2 (SNAI2), Twist1, vimentin (VIM), and MMP2 and the reexpression of E-cadherin (CDH1). The N4ICD-induced phenotypic switch also resulted in significantly reduced tumor growth in vivo Immunohistochemical analysis of primary human melanomas and cutaneous metastases revealed a significant correlation between Notch4 and E cadherin expression. Mechanistically, we demonstrate that N4ICD induced the expression of the transcription factors Hey1 and Hey2, which bound directly to the promoter regions of Snail2 and Twist1 and repressed gene transcription, as determined by EMSA and luciferase assays. Taken together, our findings indicate a role for Notch4 as a tumor suppressor in melanoma, uncovering a potential explanation for the poor clinical efficacy of Notch inhibitors observed in this setting. Cancer Res; 76(7); 1690-7. (c)2016 AACR. PMID- 26801979 TI - Erratum to: Analysis of in vitro ADCC and clinical response to trastuzumab: possible relevance of FcgammaRIIIA/FcgammaRIIA gene polymorphisms and HER-2 expression levels on breast cancer cell lines. PMID- 26801981 TI - Dietary profile of patients with Stargardt's disease and Retinitis Pigmentosa: is there a role for a nutritional approach? AB - BACKGROUND: Stargardt's disease (STGD) and Retinitis Pigmentosa (RP) are inherited retinal degenerations that may be affected, in opposite way, by diet. METHODS: Dietary profile was assessed in 24 patients with STGD and in 56 patients with RP. We documented in only 6 out of 24 (25%) STGD patients a daily intake of vitamin A within the recommended range while 14/24 (58.3%) reported a high daily intake and 4/24 (16.7%) showed a low daily intake. With regard to RP, 4/56 (7.1%) reported to be within the recommended range, 37/56 (66.1%) reported high daily intake and 15/56 (26.8%) showed low daily intake of vitamin A. RESULTS: Interestingly, STGD patients with low vitamin A intake (<600 ug RAE/day) showed significantly better visual acuity with respect to those introducing higher intake of vitamin A. CONCLUSION: The present study suggests insuitable nutrient intakes among patients with STGD and RP, especially for daily intake of vitamin A. The results may be used to provide tailored nutritional interventions in these patients. PMID- 26801982 TI - Atypical uterine leiomyoma: a case report and review of the literature. AB - BACKGROUND: Atypical uterine leiomyomas show benign behavior. However, the distinction between leiomyomas and leiomyosarcomas may at times be problematic. We report a rare case of atypical uterine leiomyoma. We try to investigate potential immunohistochemical parameters that could be essential to distinguish cases of malignant smooth muscle tumors and those of uncertain or borderline histology. CASE PRESENTATION: A 56-year-old white ethnic Albanian woman from Kosovo presented with uterine bleeding because of uterine multiple leiomyomas. A hysterectomy with unilateral adnexectomy was performed. Her hysterectomy specimen contained multiple leiomyomas in submucosal, intramural and subserosal locations. The leiomyomas were well demarcated, firm and white with a whorled cut surface and one had foci of hemorrhage. Histology of most of the leiomyomas showed a whorled (fascicular) pattern of smooth muscle bundles separated by well vascularized connective tissue. Smooth muscle cells were elongated with eosinophilic or occasional fibrillar cytoplasm and distinct cell membranes. Some of them developed areas of degeneration including hyaline change, with less than five mitotic figures per ten high power fields in most mitotically active areas, and no significant atypia. One leiomyoma was characterized by moderately to severely pleomorphic atypical tumor cells with low mitotic counts and no coagulative tumor cell necrosis. Immunohistochemistry showed strong immunoreactivity for vimentin, smooth muscle actin and desmin, while cyclin dependent kinase inhibitor 2A (p16), and B-cell lymphoma 2 (bcl-2) showed focal immunoreactivity, estrogen and progesterone were positive, Ki-67 expressed a low proliferation index, whereas p21 and tumor suppressor gene p53 were negative. CONCLUSIONS: The combination of evaluation of conventional morphologic criteria with cyclin-dependent kinase inhibitor 2A (p16), p21, progesterone, B-cell lymphoma 2, tumor suppressor gene p53 and Ki-67 expression may be of great value in the assessment of uterine smooth muscle tumors of uncertain or borderline histology. PMID- 26801980 TI - Effects of the pattern of glucocorticoid replacement on neural processing, emotional reactivity and well-being in healthy male individuals: study protocol for a randomised controlled trial. AB - BACKGROUND: Deviation from the physiological glucocorticoid dynamics (circadian and underlying ultradian rhythmicity) is a common characteristic of various neuropsychiatric and endocrine disorders as well as glucocorticoid-based therapeutics. These states may be accompanied by neuropsychiatric symptomatology, suggesting continuous dynamic glucocorticoid equilibrium is essential for brain homeostasis. METHODS/DESIGN: The study consists of two parts. The preliminary stage of the study aims to validate (technically and pharmacologically) and optimise three different patterns of systemic cortisol administration in man. These patterns are based on the combinatory administration of metyrapone, to suppress endogenous cortisol production, and concurrent hydrocortisone replacement. The second, subsequent, core part of the study is a randomised, double-blinded, placebo-controlled, crossover study, where participants (healthy male individuals aged 18-60 years) will undergo all three hydrocortisone replacement schemes. During these infusion regimes, we plan a number of neurobehavioural tests and imaging of the brain to assess neural processing, emotional reactivity and perception, mood and self-perceived well-being. The psychological tests include: ecological momentary assessment, P1vital Oxford Emotional Test Battery and Emotional Potentiated Startle Test, Leeds Sleep Evaluation Questionnaire and the visual working memory task (n-back). The neuroimaging protocol combines magnetic resonance sequences that capture data related to the functional and perfusion status of the brain. DISCUSSION: Results of this clinical trial are designed to evaluate the impact (with possible mechanistic insights) of different patterns of daily glucocorticoid dynamics on neural processing and reactivity related to emotional perception and mood. This evidence should contribute to the optimisation of the clinical application of glucocorticoid-based therapeutics. TRIAL REGISTRATION: UK Clinical Research Network, IRAS Ref: 106181, UKCRN-ID-15236 (23 October 2013). PMID- 26801983 TI - Space GlucoseControl system for blood glucose control in intensive care patients- a European multicentre observational study. AB - BACKGROUND: Glycaemia control (GC) remains an important therapeutic goal in critically ill patients. The enhanced Model Predictive Control (eMPC) algorithm, which models the behaviour of blood glucose (BG) and insulin sensitivity in individual ICU patients with variable blood samples, is an effective, clinically proven computer based protocol successfully tested at multiple institutions on medical and surgical patients with different nutritional protocols. eMPC has been integrated into the B.Braun Space GlucoseControl system (SGC), which allows direct data communication between pumps and microprocessor. The present study was undertaken to assess the clinical performance and safety of the SGC for glycaemia control in critically ill patients under routine conditions in different ICU settings and with various nutritional protocols. METHODS: The study endpoints were the percentage of time the BG was within the target range 4.4 - 8.3 mmol.l( 1), the frequency of hypoglycaemic episodes, adherence to the advice of the SGC and BG measurement intervals. BG was monitored, and insulin was given as a continuous infusion according to the advice of the SGC. Nutritional management (enteral, parenteral or both) was carried out at the discretion of each centre. RESULTS: 17 centres from 9 European countries included a total of 508 patients, the median study time was 2.9 (1.9-6.1) days. The median (IQR) time-in-target was 83.0 (68.7-93.1) % of time with the mean proposed measurement interval 2.0 +/- 0.5 hours. 99.6% of the SGC advices on insulin infusion rate were accepted by the user. Only 4 episodes (0.01% of all BG measurements) of severe hypoglycaemia <2.2 mmol.l(-1) in 4 patients occurred (0.8%; 95% CI 0.02-1.6%). CONCLUSION: Under routine conditions and under different nutritional protocols the Space GlucoseControl system with integrated eMPC algorithm has exhibited its suitability for glycaemia control in critically ill patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01523665. PMID- 26801985 TI - Protective effect of Bu-Zhong-Yi-Qi decoction, the water extract of Chinese traditional herbal medicine, on 5-fluorouracil-induced intestinal mucositis in mice. AB - Intestinal mucositis is a serious toxic side effect of 5-fluorouracil (5-FU) treatment. Bu-Zhong-Yi-Qi decoction (BZYQD), a water extract of Chinese traditional herbal medicine, is widely used in chemotherapy in Asia as an alternative treatment to reduce the side effects of chemotherapy. However, the mechanism is unknown. To evaluate its mechanism, we investigated the effect of BZYQD on 5-FU-induced intestinal mucositis in mice, especially with regard to apoptosis in the intestinal mucosal epithelia. In the present study, mice were divided into three groups: control, 5-FU, and 5-FU + BZYQD. Mice in the 5-FU and 5-FU + BZYQD groups were administered 5-FU (100 mg/kg/day, intraperitoneally) for 6 days, and the mice in the latter group were given BZYQD (8 g/kg/day, intragastrically) beginning 4 days before 5-FU and continuing until the termination of the experiment. Loss in body weight and diarrhea during the 5-FU treatment were significantly attenuated by administration of BZYQD. The morphological signs of intestinal damage, including shortened villi height, crypt destruction, apoptosis, and necrosis, in intestinal mucosal epithelia were also reversed, accompanied by reduced neutrophil infiltration, nitrite levels, and inflammatory factors (tumor necrosis factor alpha and interleukin 1beta) and increased levels of reduced glutathione. These results suggest that BZYQD inhibits 5-FU-induced intestinal mucositis, and this effect may be due to the reduction in apoptosis and necrosis in intestinal mucosal epithelia via the suppression of inflammatory cytokine upregulation. In conclusion, inhibiting cytokine-mediated apoptosis or necrosis can be the molecular mechanism by which BZYQD reduces the gastrointestinal side effects of cancer chemotherapy. PMID- 26801984 TI - The impact of the World Health Organization 8-steps in wheelchair service provision in wheelchair users in a less resourced setting: a cohort study in Indonesia. AB - BACKGROUND: For people who have a mobility impairment, access to an appropriate wheelchair is an important step towards social inclusion and participation. The World Health Organization Guidelines for the Provision of Manual Wheelchairs in Less Resourced Settings emphasize the eight critical steps for appropriate wheelchair services, which include: referral, assessment, prescription, funding and ordering, product preparation,fitting and adjusting, user training, and follow-up and maintenance/repairs. The purpose of this study was to investigate how the provision of wheelchairs according to the World Health Organization's service provision process by United Cerebral Palsy Wheels for Humanity in Indonesia affects wheelchair recipients compared to wait-listed controls. METHODS: This study used a convenience sample (N = 344) of Children, Children with proxies, Adults, and Adults with proxies who were on a waiting list to receive a wheelchair as well as those who received one. Interviews were conducted at baseline and a 6 month follow-up to collect the following data: Demographics and wheelchair use questions, the World Health Organization Quality of Life-BREF, Functional Mobility Assessment, Craig Handicap Assessment Recording Technique Short Form. The Wheelchair Assessment Checklist and Wheelchair Skills Test Questionnaire were administered at follow up only. RESULTS: 167 participants were on the waiting list and 142 received a wheelchair. Physical health domain in the World Health Organization Quality of Life-BREF improved significantly for women who received a wheelchair (p = 0.044) and environmental health improved significantly for women and men who received a wheelchair as compared to those on the waiting list (p < 0.017). Satisfaction with the mobility device improved significantly for Adults with proxies and Children with proxies as compared to the waiting list (p < 0.022). Only 11 % of Adults who received a wheelchair reported being able to perform a "wheelie". The condition of Roughrider wheelchairs was significantly better than the condition of kids wheelchairs for Children with proxies as measured by the Wheelchair Assessment Checklist (p = 0.019). CONCLUSIONS: Wheelchair provision according to World Health Organization's 8-Steps in a less-resourced setting has a range of positive outcomes including increased satisfaction with the mobility device and better quality of life. Wheelchair provision service could be improved by providing more hours of wheelchair skills training. There is a need for outcome measures that are validated across cultures and languages. PMID- 26801986 TI - The protective effects of carvacrol and thymol against paracetamol-induced toxicity on human hepatocellular carcinoma cell lines (HepG2). AB - Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 uM) were tested on cultured HepG2 cells. N Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor alpha and interleukin 1beta. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol. PMID- 26801988 TI - Surface vimentin is critical for the cell entry of SARS-CoV. AB - BACKGROUND: Severe acute respiratory syndrome coronavirus (SARS-CoV) caused a global panic due to its high morbidity and mortality during 2002 and 2003. Soon after the deadly disease outbreak, the angiotensin-converting enzyme 2 (ACE2) was identified as a functional cellular receptor in vitro and in vivo for SARS-CoV spike protein. However, ACE2 solely is not sufficient to allow host cells to become susceptible to SARS-CoV infection, and other host factors may be involved in SARS-CoV spike protein-ACE2 complex. RESULTS: A host intracellular filamentous cytoskeletal protein vimentin was identified by immunoprecipitation and LC-MS/MS analysis following chemical cross-linking on Vero E6 cells that were pre incubated with the SARS-CoV spike protein. Moreover, flow cytometry data demonstrated an increase of the cell surface vimentin level by 16.5 % after SARS CoV permissive Vero E6 cells were treated with SARS-CoV virus-like particles (VLPs). A direct interaction between SARS-CoV spike protein and host surface vimentin was further confirmed by far-Western blotting. In addition, antibody neutralization assay and shRNA knockdown experiments indicated a vital role of vimentin in cell binding and uptake of SARS-CoV VLPs and the viral spike protein. CONCLUSIONS: A direct interaction between vimentin and SARS-CoV spike protein during viral entry was observed. Vimentin is a putative anti-viral drug target for preventing/reducing the susceptibility to SARS-CoV infection. PMID- 26801991 TI - The Paris terror attacks, mental health and the spectre of fear. PMID- 26801990 TI - Do health reforms work? PMID- 26801987 TI - Co-infection of Epstein-Barr virus and human papillomavirus in human tumorigenesis. AB - Viral infections contribute to approximately 12% of cancers worldwide, with the vast majority occurring in developing countries and areas. Two DNA viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), are associated with 38% of all virus-associated cancers. The probability of one patient infected with these two distinct types of viruses is increasing. Here, we summarize the co infection of EBV and HPV in human malignancies and address the possible mechanisms for the co-infection of EBV and HPV during tumorigenesis. PMID- 26801989 TI - Whole grain consumption trends and associations with body weight measures in the United States: results from the cross sectional National Health and Nutrition Examination Survey 2001-2012. AB - BACKGROUND: The purpose of this study was (1) to describe intakes of total grain and whole grain in the United States over the past 12 years and major dietary sources, and (2) to determine the relationship between whole grain intake and adiposity measures for children and adults. METHODS: Cross-sectional dietary data from the continuous National Health and Nutrition Examination Survey 2001-12 (6 2 year cycles) for children 6-18 years (n = 15,280) and adults 19+ years (n = 29,683) were linked to the My Pyramid and Food Patterns Equivalents Databases to assess daily intake of total grain and whole grain. These populations were classified into groups based on average whole grain intake: 0 ounce equivalents (oz eq)/day, > 0 and <1 oz eq/day, and >=1 oz eq/day. Within these classifications, body mass index, waist circumference, and percent overweight/obese were identified. Regression and logistic regression analyses were used to assess associations between these dependent variables and whole grain intake. RESULTS: Adults consumed a mean 0.72 whole grain oz eq/day in 2001 02 and 0.97 oz eq/day in 2011-12 and children consumed a mean 0.56 whole grain oz eq/day in 2001-02 and 0.74 oz eq/day in 2011-12. While over 70 % of children and 60 % of adults met daily intake recommendations for total grain, less than 1.0 and 8.0 % percent of children and adults, respectively, met whole grain recommendations in 2011-12. Adults and children who consumed whole grain had significantly better intakes of nutrients and dietary fiber compared to non consumers. From 2001 to 2012, grain mixed dishes and yeast breads were the leading sources of total grain, while yeast breads and ready to eat cereals were the leading sources of whole grain for both children and adults. Multiple regression analysis showed a significant, inverse relationship between body mass index and waist circumference with respect to whole grain intake after adjustment for covariates in both children and adults (p < 0.05). Similarly, logistic regression analysis showed a significant inverse relationship between percent overweight/obese and whole grain intake (p < 0.05). CONCLUSIONS: Although most children and adults meet daily intake goals for grain foods overall, whole grain as a portion of total grain intake continues to be consumed at levels well below recommendations. The data from the current study suggest that greater whole grain consumption is associated with better intakes of nutrients and healthier body weight in children and adults. Continued efforts to promote increased intake of whole grain foods are warranted. PMID- 26801992 TI - How much does it cost? PMID- 26801993 TI - Dismantling the NHS. PMID- 26801994 TI - Jerome Cornfield's Bayesian approach to assessing interim results in clinical trials. PMID- 26801998 TI - Cognitive behavioural therapy for ADHD in adults: systematic review and meta analyses. AB - Systematically review and analyse the efficacy of CBT versus treatment as usual in adults with ADHD. The literature was systematically searched ending the 28 March 2014. Standardised mean differences (SMD) and 95% confidence intervals were calculated. CBT was efficacious in reducing symptoms of ADHD (SDM -1.0, 95% CI 1.5 to -0.5) when evaluated by the patients, but not when evaluated by a clinician. Symptoms of depression and anxiety were significantly reduced when self-reported (SMD -1.0, 95% CI -1.6 to -0.5 and -1.0, 95% CI -1.3 to -0.3, respectively) and evaluated by a clinician (SMD -0.9, 95% CI -1.7 to -0.2 and 0.9, 95% CI -1.6 to -0.1). The clinical global impression scores improved more in the group randomised to CBT (-1.0; 95% CI -1.6 to -0.4). CBT seems efficacious in some domains affecting adult patients with ADHD, but needs further evaluation. PMID- 26801999 TI - Comparison of smith-petersen osteotomy, pedicular subtraction osteotomy, and poly segmental wedge osteotomy in treating rigid thoracolumbar kyphotic deformity in ankylosing spondylitis a systematic review and meta-analysis. AB - BACKGROUND: This study aimed to compare Smith-Petersen osteotomy (SPO), poly segmental wedge osteotomy (PWO) and pedicular subtraction osteotomy (PSO) in patients with rigid thoracolumbar kyphosis primarily caused by ankylosing spondylitis. The efficiency, efficacy and safety of these three osteotomies have not been compared systematically, and no illness-oriented surgical type selection strategy for the treatment of ankylosing spondylitis related to non-angular kyphosis has been reported. METHODS: The inclusion and exclusion criteria were defined, and 19 electronic databases were searched for eligible studies without language limitations. For the included studies, data extraction, bias analysis, heterogeneity analysis and quantitative analysis were performed to analyze the correction of kyphosiskyphosis and the incidence of complications. RESULTS: Nine comparative studies that met the standards were included with a total of 539 patients that underwent SPO (n = 120), PWO (n = 119), or PSO (n = 300). The correction of kyphosis by PSO was 8.74 degrees [95% CI: 0.7-16.78] greater than SPO. The correction of kyphosis by PWO was 13.88 degrees [95 % CI: 9.25-18.51] greater than SPO. For local biomechanical complications, the pooled risk ratio of PWO to PSO was 1.97 [95 % CI: 1.03-3.77]. For blood loss, PSO was 806.42 ml [95% CI: 591.72-1021.12] greater than SPO and 566.76 ml [95 % CI: 129.80-1003.72] greater than PWO. CONCLUSIONS: To treat rigid thoracolumbar kyphosis, PSO showed higher efficiency and efficacy than SPO, and PWO had a higher efficacy than SPO. The risk of local biomechanical complications was greater in PWO than PSO. Bleeding was more severe in PSO than in SPO or PWO. The incidence of neural complications and systemic complications was similar. PMID- 26802000 TI - MRI and clinical features of Langerhans cell histiocytosis (LCH) in the pelvis and extremities: can LCH really look like anything? AB - OBJECTIVE: To assess clinical and MRI features of Langerhans cell histiocytosis in the pelvis and extremities. MATERIALS AND METHODS: The MRI and clinical features of 21 pathologically proven cases of LCH involving the pelvis and extremities were studied. Multiple characteristics of the lesions were evaluated (location, size, T1/ T2/post-contrast features, perilesional bone and soft tissue signal, endosteal scalloping, periosteal reaction, soft tissue mass, pathologic fracture). Pre-biopsy radiologic diagnoses were collected from the original clinical reports. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), temperature, and white blood cell count (WBC) were collected at the time of diagnosis when available. RESULTS: The locations of the LCH lesions included five humerus, four femur, five ilium, one tibia, one clavicle, and three scapula. Lesional size ranged from 1.8 to 7.1 cm, with a mean of 3.6 cm. All lesions demonstrated perilesional bone marrow edema, periosteal reaction, endosteal scalloping, and post-contrast enhancement. An associated soft tissue mass was present in 15/21 (71.4 %). Clinically, the WBC, ESR, and CRP were elevated in 2/14 (14 %), 8/12 (67 %), and 4/10 (40 %) of cases, respectively. Fever was documented in 1/15 (7 %) patients and pain was reported in 15/15 (100 %). CONCLUSIONS: The clinical and radiologic features of LCH in the pelvis and extremities overlap with infection and malignancy, but LCH must be considered in the differential diagnosis, as it routinely presents with aggressive MRI features, including endosteal scalloping, periosteal reaction, perilesional edema, and a soft tissue mass. Furthermore, an unknown skeletal lesion at presentation without aggressive MRI features is unlikely to represent LCH. PMID- 26802001 TI - Treatments for Kienbock disease: what the radiologist needs to know. AB - The etiology of Kienbock disease, or avascular necrosis of the lunate, is controversial, and there are a myriad of treatments aimed at correcting the various hypothesized pathologies. Interventions to reduce mechanical stress on the lunate have been used for decades, including radial osteotomy with or without radial shortening, ulnar lengthening and metaphyseal core decompression procedures. However, these procedures require preservation of lunate architecture. Newer procedures to revascularize the lunate bone have emerged in the last 10 years, such as pedicled corticoperiosteal vascularized bone grafting. Once there is collapse of the radiocarpal joint or midcarpal arthrosis, the conventional treatments have included proximal row carpectomy and complete or partial wrist joint arthrodesis. Newer salvage procedures such as lunate excision with autologous or synthetic interposition grafts are now being used when possible. As this disease is relatively rare, radiologists may not be familiar with the expected post-operative radiologic findings and complications, especially of the newer treatments. The goals of this paper are to review the available treatment options and their expected appearance on postoperative imaging, with discussion of possible complications when appropriate. PMID- 26802003 TI - RETRACTED ARTICLE: Predictors of institutionalization among home-dwelling older Finnish people: a 22-year follow-up study. PMID- 26802002 TI - Respiratory muscle strength in relation to sarcopenia in elderly cardiac patients. AB - BACKGROUND AND AIMS: Little information exists on the relation between respiratory muscle strength such as maximum inspiratory muscle pressure (MIP) and sarcopenia in elderly cardiac patients. The present study aimed to determine the differences in MIP, and cutoff values for MIP according to sarcopenia in elderly cardiac patients. METHODS: We enrolled 63 consecutive elderly male patients aged >=65 years with cardiac disease in this cross-sectional study. Sarcopenia was defined based on the European Working Group on Sarcopenia in Older People algorithm, and, accordingly, the patients were divided into two groups: the sarcopenia group (n = 24) and non-sarcopenia group (n = 39). The prevalence of sarcopenia in cardiac patients and MIP in the patients with and without sarcopenia were assessed to determine cutoff values of MIP. RESULTS: After adjustment for body mass index, the MIP in the sarcopenia group was significantly lower than that in the non-sarcopenia group (54.7 +/- 36.8 cmH2O; 95 % CI 42.5 72.6 vs. 80.7 +/- 34.7 cmH2O; 95 % CI 69.5-92.0; F = 4.89, p = 0.029). A receiver operating characteristic curve analysis of patients with and without sarcopenia identified a cutoff value for MIP of 55.6 cmH2O, with a sensitivity of 0.76, 1 specificity of 0.37, and AUC of 0.70 (95 % CI 0.56-0.83; p = 0.01) in the study patients. CONCLUSION: Compared with elderly cardiac patients without sarcopenia, MIP in those with sarcopenia may be negatively affected. The MIP cutoff value reported here may be a useful minimum target value for identifying elderly male cardiac patients with sarcopenia. PMID- 26802004 TI - A Randomized Control Trial for Evaluating Efficacies of Two Online Cognitive Interventions With and Without Fear-Appeal Imagery Approaches in Preventing Unprotected Anal Sex Among Chinese Men Who Have Sex with Men. AB - Fear appeal approach has been used in health promotion, but its effectiveness has been mixed. It has not been well applied to HIV prevention among men who have sex with men (MSM). The present study developed and evaluated the relative efficacy of three online interventions (SC: STD-related cognitive approach, SCFI: STD related cognitive plus fear appeal imagery approach, Control: HIV-related information based approach) in reducing prevalence of unprotected anal intercourse (UAI) among 396 MSM using a randomized controlled trial design. Participants' levels of fear-related emotions immediately after watching the assigned intervention materials were also assessed. Participants were evaluated at baseline and 3 months after the intervention. Results showed that participants in the SCFI scored significantly higher in the instrument assessing fear after the watching the intervention materials. However, no statistically significant differences were found across the three groups in terms of UAI at Month 3. Some significant within-group reductions in some measures of UAI were found in three groups. Further studies are warranted to test the role of fear appeal in HIV prevention. PMID- 26802005 TI - An analysis of heart donation after circulatory determination of death. AB - BACKGROUND: Heart donation after circulatory determination of death (DCDD) has provoked ethical debate focused primarily on whether heart DCDD donors are dead when death is declared and when organs are procured. OBJECTIVE AND DESIGN: We rigorously analyse whether four heart DCDD programmes (Cape Town, Denver, Australia, Cambridge) respect the dead donor rule (DDR), according to six criteria of death: irreversible cessation of all bodily cells function (or organs), irreversible cessation of heart function, irreversible cessation of circulation, permanent cessation of circulation, irreversible cessation of brain function and permanent cessation of brain function. CONCLUSIONS: Only death criteria based on permanency are compatible with the DDR under two conditions: (1) a minimum stand-off period of 5 min to ensure that autoresuscitation is impossible and that all brain functions have been lost and (2) no medical intervention is undertaken that might resume bodily or brain circulation. By our analysis, only the Australia heart DCDD programme using a stand-off period of 5 min respects the DDR when the criteria of death are based on permanency. PMID- 26802006 TI - Balance Exercises Circuit improves muscle strength, balance, and functional performance in older women. AB - This study introduces the Balance Exercises Circuit (BEC) and examines its effects on muscle strength and power, balance, and functional performance in older women. Thirty-five women aged 60+ (mean age = 69.31, SD = 7.35) were assigned to either a balance exercises group (BG, n = 14) that underwent 50-min sessions twice weekly, of a 12-week BEC program, or a wait-list control group (CG, n = 21). Outcome measures were knee extensor peak torque (PT), rate of force development (RFD), balance, Timed Up & Go (TUG), 30-s chair stand, and 6-min walk tests, assessed at baseline and 12 weeks. Twenty-three participants completed follow-up assessments. Mixed analysis of variance models examined differences in outcomes. The BG displayed improvements in all measures at follow-up and significantly improved compared with CG on, isokinetic PT60, PT180 (p = 0.02), RFD (p < 0.05), balance with eyes closed (p values range .02 to <.01) and TUG (p = 0.03), all with medium effect sizes. No changes in outcome measures were observed in the CG. BEC improved strength, power, balance, and functionality in older women. The BEC warrants further investigation as a fall prevention intervention. PMID- 26802007 TI - In vitro characterization of the NAD+ synthetase NadE1 from Herbaspirillum seropedicae. AB - Nicotinamide adenine dinucleotide synthetase enzyme (NadE) catalyzes the amination of nicotinic acid adenine dinucleotide (NaAD) to form NAD(+). This reaction represents the last step in the majority of the NAD(+) biosynthetic routes described to date. NadE enzymes typically use either glutamine or ammonium as amine nitrogen donor, and the reaction is energetically driven by ATP hydrolysis. Given the key role of NAD(+) in bacterial metabolism, NadE has attracted considerable interest as a potential target for the development of novel antibiotics. The plant-associative nitrogen-fixing bacteria Herbaspirillum seropedicae encodes two putative NadE, namely nadE1 and nadE2. The nadE1 gene is linked to glnB encoding the signal transduction protein GlnB. Here we report the purification and in vitro characterization of H. seropedicae NadE1. Gel filtration chromatography analysis suggests that NadE1 is an octamer. The NadE1 activity was assayed in vitro, and the Michaelis-Menten constants for substrates NaAD, ATP, glutamine and ammonium were determined. Enzyme kinetic and in vitro substrate competition assays indicate that H. seropedicae NadE1 uses glutamine as a preferential nitrogen donor. PMID- 26802008 TI - The emergence of epitheliocystis in the upper Rhone region: evidence for Chlamydiae in wild and farmed salmonid populations. AB - We present the first study comparing epitheliocystis in a wild and farmed salmonid in Europe. Sampling three tributaries to the Lake Geneva, including one from headwaters to river mouth, revealed an unequal distribution of epitheliocystis in brown trout (Salmo trutta). When evaluated histologically and comparing sites grouped as wild versus farm, the probability of finding infected trout is higher on farms. In contrast, the infection intensities, as estimated by the number of cysts per gill arch, were higher on average and showed maximum values in the wild trout. Sequence analysis showed the most common epitheliocystis agents were Candidatus Piscichlamydia salmonis, all clustering into a single clade, whereas Candidatus Clavichlamydia salmonicola sequences cluster in two closely related subspecies, of which one was mostly found in farmed fish and the other exclusively in wild brown trout, indicating that farms are unlikely to be the source of infections in wild trout. A detailed morphological analysis of cysts using transmission electron microscopy revealed unique features illustrating the wide divergence existing between Ca. P. salmonis and Ca. C. salmonicola within the phylum Chlamydiae. PMID- 26802009 TI - Nocardioides flava sp. nov., isolated from rhizosphere of poppy plant, Republic of Korea. AB - Phylogenetic and taxonomic characterization was performed for bacterium, designated strain THG-DN5.4(T), isolated from the rhizosphere of poppy plant collected from Gyeryongsan, Republic of Korea. Strain THG-DN5.4(T) consists of Gram-stain-positive, aerobic, non-motile rods. The bacteria grow optimally at 18 30 degrees C, at pH 7.0 and in the presence of 0.5-1.0 % NaCl. Based on 16S rRNA gene sequence analysis, strain THG-DN5.4(T) was found to be most closely related to Nocardioides nitrophenolicus KCTC 047BP(T), followed by Nocardioides ginsengisoli KCTC 19135(T), Nocardioides kongjuensis KCTC 19054(T), Nocardioides simplex KACC 20620(T), Nocardioides aromaticivorans KACC 20613(T), Nocardioides daeguensis KCTC 19799(T) and Nocardioides caeni KCTC 19600(T). The DNA-DNA relatedness between strain THG-DN5.4(T) and closely related phylogenetic neighbors was below 45.0 %, and the DNA G+C content of strain THG-DN5.4(T) was 70.8 mol%. An isoprenoid quinone was identified as MK-8(H4). Strain THG-DN5.4(T) was characterized chemotaxonomically as having LL-diaminopimelic acid in the cell wall peptidoglycan. The polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol, some unidentified aminolipids and some unidentified polar lipids. iso-C16:0 and C18:1 omega9c were identified as the major fatty acids present in THG-DN5.4(T). On the basis of a polyphasic taxonomic study, strain THG DN5.4(T) is considered to represent a novel species of the genus Nocardioides, for which the name Nocardioides flava sp. nov. is proposed. The type strain is THG-DN5.4(T) (=KCTC 39606(T)=CCTCC AB 2015298(T)). PMID- 26802010 TI - Community-Based ECG Monitoring System for Patients with Cardiovascular Diseases. AB - This study aims to develop a community-based electrocardiogram (ECG) monitoring system for cardiac outpatients to wirelessly detect heart rate, provide personalized healthcare, and enhance interactive social contact because of the prevalence of deaths from cardiovascular disease and the growing problem of aging in the world. The system not only strengthens the performance of the ECG monitoring system but also emphasizes the ergonomic design of wearable devices and user interfaces. In addition, it enables medical professionals to diagnose cardiac symptoms remotely and electronically manage medical reports and suggestions. The experimental result shows high performance of the dry electrode, even in dynamic conditions. The comparison result with different ECG healthcare systems shows the essential factors that the system should possess and the capability of the proposed system. Finally, a user survey was conducted based on the unified theory of acceptance and users of technology (UTAUT) model. PMID- 26802011 TI - A 3-Month Randomized Controlled Pilot Trial of a Patient-Centered, Computer-Based Self-Monitoring System for the Care of Type 2 Diabetes Mellitus and Hypertension. AB - This study was performed to evaluate the effects of a patient-centered, tablet computer-based self-monitoring system for chronic disease care. A 3-month randomized controlled pilot trial was conducted to compare the use of a computer based self-monitoring system in disease self-care (intervention group; n = 33) with a conventional self-monitoring method (control group; n = 30) in patients with type 2 diabetes mellitus and/or hypertension. The system was equipped with a 2-in-1 blood glucose and blood pressure monitor, a reminder feature, and video based educational materials for the care of the two chronic diseases. The control patients were given only the 2-in-1 monitor for self-monitoring. The outcomes reported here included the glycated hemoglobin (HbA1c) level, fasting blood glucose level, systolic blood pressure, diastolic blood pressure, chronic disease knowledge, and frequency of self-monitoring. The data were collected at baseline and at 1-, 2-, and 3-month follow-up visits. The patients in the intervention group had a significant decrease in mean systolic blood pressure from baseline to 1 month (p < 0.001) and from baseline to 3 months (p = 0.043) compared with the control group. Significant improvements in the mean diastolic blood pressure were seen in the intervention group compared with the control group after 1 month (p < 0.001) and after 2 months (p = 0.028), but the change was not significant after 3 months. No significant differences were observed between the groups in the fasting blood glucose level, the HbA1c level, or chronic disease knowledge. The frequency of self-monitoring of blood glucose level and blood pressure was similar in both groups. The performances of the tablet computer-assisted and conventional disease self-monitoring appear to be useful to support/maintain blood pressure and diabetes control. The beneficial effects of the use of electronic self-care resources and support provided via mobile technologies require further confirmation in longer-term, larger trials. PMID- 26802012 TI - Extended source model for diffusive coupling. AB - Motivated by the prevailing approach to diffusion coupling phenomena which considers point-like diffusing sources, we derived an analogous expression for the concentration rate of change of diffusively coupled extended containers. The proposed equation, together with expressions based on solutions to the diffusion equation, is intended to be applied to the numerical solution of systems exclusively composed of ordinary differential equations, however is able to account for effects due the finite size of the coupled sources. PMID- 26802013 TI - Cell wall matrix polysaccharide distribution and cortical microtubule organization: two factors controlling mesophyll cell morphogenesis in land plants. AB - BACKGROUND AND AIMS: This work investigates the involvement of local differentiation of cell wall matrix polysaccharides and the role of microtubules in the morphogenesis of mesophyll cells (MCs) of three types (lobed, branched and palisade) in the dicotyledon Vigna sinensis and the fern Asplenium nidus. METHODS: Homogalacturonan (HGA) epitopes recognized by the 2F4, JIM5 and JIM7 antibodies and callose were immunolocalized in hand-made leaf sections. Callose was also stained with aniline blue. We studied microtubule organization by tubulin immunofluorescence and transmission electron microscopy. RESULTS: In both plants, the matrix cell wall polysaccharide distribution underwent definite changes during MC differentiation. Callose constantly defined the sites of MC contacts. The 2F4 HGA epitope in V. sinensis first appeared in MC contacts but gradually moved towards the cell wall regions facing the intercellular spaces, while in A. nidus it was initially localized at the cell walls delimiting the intercellular spaces, but finally shifted to MC contacts. In V. sinensis, the JIM5 and JIM7 HGA epitopes initially marked the cell walls delimiting the intercellular spaces and gradually shifted in MC contacts, while in A. nidus they constantly enriched MC contacts. In all MC types examined, the cortical microtubules played a crucial role in their morphogenesis. In particular, in palisade MCs, cortical microtubule helices, by controlling cellulose microfibril orientation, forced these MCs to acquire a truncated cone-like shape. Unexpectedly in V. sinensis, the differentiation of colchicine-affected MCs deviated completely, since they developed a cell wall ingrowth labyrinth, becoming transfer-like cells. CONCLUSIONS: The results of this work and previous studies on Zea mays (Giannoutsou et al., Annals of Botany 2013; 112: : 1067-1081) revealed highly controlled local cell wall matrix differentiation in MCs of species belonging to different plant groups. This, in coordination with microtubule-dependent cellulose microfibril alignment, spatially controlled cell wall expansion, allowing MCs to acquire their particular shape. PMID- 26802014 TI - The clinical outcome of cardiac resynchronization therapy in post-surgical valvular cardiomyopathy. AB - AIMS: Trials have shown that cardiac resynchronization therapy (CRT) is effective in patients with 'non-ischaemic cardiomyopathy'. Patients with post-surgical valvular cardiomyopathy (PSVCM) have been excluded from such trials. We sought to compare the clinical outcome of CRT in patients with PSVCM, idiopathic dilated cardiomyopathy (IDCM), or ischaemic cardiomyopathy (ICM). METHODS AND RESULTS: Clinical events and response to CRT were quantified in 556 patients (PSVCM = 38; IDCM = 165; ICM = 353) over 4.52 years [median, inter-quartile range (IQR): 4.42]. Response to CRT was defined as survival for >=1 year free of hospitalizations plus improvement by >=1 NYHA class or >=25% in 6-min walking distance. Cardiac resynchronization therapy was initiated at 5.86 years (median, IQR: 9.86) after aortic valve replacement (73.7%) or mitral valve replacement/repair (44.7%). Compared with PSVCM, IDCM was associated with a lower total mortality [hazards ratio, HR: 0.54 (95% confidence interval, CI 0.34 0.84)], cardiac mortality [HR: 0.43 (95% CI 0.26-0.70)], and total mortality or major adverse cardiovascular events [HR: 0.57 (95% CI 0.37-0.87)], independent of known confounders. Compared with PSVCM, ICM was associated with a similar risk of death from pump failure [HR: 0.83 (95% CI 0.50-1.37)] and IDCM was associated with a lower risk [HR: 0.46 (95% CI 0.26-0.82)]. Response to CRT was similar across the groups. CONCLUSIONS: Compared with IDCM, PSVCM was associated with a worse outcome after CRT. Outcomes from PSVCM were similar to ICM. These findings indicate that PSVCM behaves very differently to IDCM after CRT. PMID- 26802017 TI - Examining factors associated with self-management skills in teenage survivors of cancer. AB - BACKGROUND: Monitoring long-term health of teenage cancer survivors is dependent on successful transition from pediatric to adult long-term follow-up (LTFU) care. This study identified factors associated with self-management skills (SMSs), an important correlate of successful transition. METHODS: Data were collected from a cross-sectional survey conducted at three Canadian hospitals between July 2011 and January 2012. The sample included 184 childhood cancer survivors aged between 15 and 19 years. Independent factors included demographic- and illness-related factors. The outcome of interest was SMSs, measured using the SMSs scale, with higher scores indicating more SMSs. RESULTS: More SMSs were associated positively with older age (beta = 1.2, 95 % confidence interval (CI) = 0.1 to 2.4), being female (beta = 4.6, 95 % CI = 1.9 to 7.4), and having a non-married parent (beta = 5.2, 95 % CI = 0.04 to 10.4). There was a negative association between SMSs and having had a central nervous system tumor (CNS) compared to having leukemia (beta = -7.9, 95 % CI = -13.5 to -2.2). CONCLUSIONS: Younger, male, and CNS tumor survivors lack SMSs. Future research is needed to explore the extent and nature of associations between SMSs and parents' marital status. IMPLICATIONS FOR CANCER SURVIVORS: Younger, male, and CNS tumor survivors should be targeted for interventions in order to ensure that adequate SMSs are attained before completion of transition. PMID- 26802016 TI - Interactions between breast cancer susceptibility loci and menopausal hormone therapy in relationship to breast cancer in the Breast and Prostate Cancer Cohort Consortium. AB - Current use of menopausal hormone therapy (MHT) has important implications for postmenopausal breast cancer risk, and observed associations might be modified by known breast cancer susceptibility loci. To provide the most comprehensive assessment of interactions of prospectively collected data on MHT and 17 confirmed susceptibility loci with invasive breast cancer risk, a nested case control design among eight cohorts within the NCI Breast and Prostate Cancer Cohort Consortium was used. Based on data from 13,304 cases and 15,622 controls, multivariable-adjusted logistic regression analyses were used to estimate odds ratios (OR) and 95 % confidence intervals (CI). Effect modification of current and past use was evaluated on the multiplicative scale. P values <1.5 * 10(-3) were considered statistically significant. The strongest evidence of effect modification was observed for current MHT by 9q31-rs865686. Compared to never users of MHT with the rs865686 GG genotype, the association between current MHT use and breast cancer risk for the TT genotype (OR 1.79, 95 % CI 1.43-2.24; P interaction = 1.2 * 10(-4)) was less than expected on the multiplicative scale. There are no biological implications of the sub-multiplicative interaction between MHT and rs865686. Menopausal hormone therapy is unlikely to have a strong interaction with the common genetic variants associated with invasive breast cancer. PMID- 26802019 TI - Treatment of severe perinatal mood disorders on a specialized perinatal psychiatry inpatient unit. AB - Perinatal patients with bipolar and psychotic mood disorder exacerbations are challenging to treat and often receive suboptimal care. We sought to examine the treatment patterns and outcomes on one of the only US-based Perinatal Psychiatry Inpatient Units (PPIU). Perinatal patients admitted to the PPIU completed self report measures at admission and before discharge. Retrospective chart reviews extracted history, diagnoses (current and past), and medication treatment. Patients who had discharge diagnoses of bipolar disorder, major depression with psychotic features, or postpartum psychosis were included. Forty-seven met the diagnostic inclusion criteria. Over an average length of stay (ALOS) of 9.96 days, there was significant improvement in depressive and anxiety symptoms and daily functioning (Work and Social Adjustment Scale). Psychiatric comorbidity was common. Polypharmacy was utilized in 87 %. The most common medications prescribed at discharge were antipsychotics, alone or in combination with mood stabilizers or antidepressants. ECT was performed in 10 % of cases. The complexity of patients with severe mood disorders or psychosis admitted to the PPIU supports individualized treatment plans that address both primary diagnosis and psychiatric comorbidities. Our results provide important information that can be disseminated to others to improve clinical outcomes for severe perinatal mood disorders. PMID- 26802020 TI - Decision-making about fertility preservation-qualitative data on young cancer patients' attitudes and needs. AB - The aim of the study was to get deeper insight into the significance of fertility in cancer patients, their attitude towards fertility preservation (FP), decisional conflicts, and patient's needs in the decision-making process. Focus groups with 12 female cancer survivors were held and revealed that the significance of fertility was high and attitude towards FP positive. Religious and ethical reservations were not negligible. Standardized decision aids were considered helpful. More support is highly in demand and specific tools would be beneficial. PMID- 26802018 TI - Renal artery sympathetic denervation: observations from the UK experience. AB - BACKGROUND: Renal denervation (RDN) may lower blood pressure (BP); however, it is unclear whether medication changes may be confounding results. Furthermore, limited data exist on pattern of ambulatory blood pressure (ABP) response particularly in those prescribed aldosterone antagonists at the time of RDN. METHODS: We examined all patients treated with RDN for treatment-resistant hypertension in 18 UK centres. RESULTS: Results from 253 patients treated with five technologies are shown. Pre-procedural mean office BP (OBP) was 185/102 mmHg (SD 26/19; n = 253) and mean daytime ABP was 170/98 mmHg (SD 22/16; n = 186). Median number of antihypertensive drugs was 5.0: 96 % ACEi/ARB; 86 % thiazide/loop diuretic and 55 % aldosterone antagonist. OBP, available in 90 % at 11 months follow-up, was 163/93 mmHg (reduction of 22/9 mmHg). ABP, available in 70 % at 8.5 months follow-up, was 158/91 mmHg (fall of 12/7 mmHg). Mean drug changes post RDN were: 0.36 drugs added, 0.91 withdrawn. Dose changes appeared neutral. Quartile analysis by starting ABP showed mean reductions in systolic ABP after RDN of: 0.4; 6.5; 14.5 and 22.1 mmHg, respectively (p < 0.001 for trend). Use of aldosterone antagonist did not predict response (p > 0.2). CONCLUSION: In 253 patients treated with RDN, office BP fell by 22/9 mmHg. Ambulatory BP fell by 12/7 mmHg, though little response was seen in the lowermost quartile of starting blood pressure. Fall in BP was not explained by medication changes and aldosterone antagonist use did not affect response. PMID- 26802021 TI - Changes in depression subtypes for women during treatment with citalopram: a latent transition analysis. AB - The aim of this study was to characterize latent subtypes of major depression and changes in these subtypes among women receiving citalopram in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Latent transition analysis was applied to data from 755 women who completed baseline and week 12 study visits in level 1 of STAR*D. Items from the self-report version of the Quick Inventory of Depressive Symptomatology were used as indicators of latent depression subtype. Four subtypes were identified at baseline and week 12. The baseline subtypes were Mild (21 %), Moderate (30 %), Severe with Increased Appetite (16 %), and Severe with Decreased Appetite (34 %). The subtypes at week 12 were Symptom Resolution (65 %), Mild (23 %), Moderate (9 %), and Severe with Psychomotor Disturbances (3 %). Women in the Moderate subtype at baseline had the greatest chance of moving to Symptom Resolution (87 %). Women in the Severe with Decreased Appetite subtype had the lowest chance of transitioning to Symptom Resolution (46 %). Depression severity and appetite distinguished depression subtypes for women before treatment with citalopram. Depression severity and psychomotor disturbances characterized the subtypes after treatment. This work highlights the need to consider how depression treatment changes different symptoms instead of relying exclusively on summary rating scores. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov , NCT00021528. PMID- 26802022 TI - High efficacy of intravesical treatment of metformin on bladder cancer in preclinical model. AB - Anticancer potential of metformin has been extensively studied. However, its anticancer clinical use remains yet to be approved since sufficient concentration on target organs could not be achieved via conventional administration. To overcome this drawback, we aim to examine the efficiency of novel intravesical treatment of metformin on syngeneic orthotopic preclinical model. Three human and one murine bladder cancer cell lines were tested in vitro for inhibitory sensitivity by MTT and cologenic assays. AMPK pathway including AKT, Erk and S6K was examined by western blot and further explored by regulating activated levels using specific inhibitors. In vivo efficacy was determined by Kaplan-Meier survival curves and measurements of body and bladder weights plus tumor biomarkers. Lactic acid and metformin levels of plasma were measured by standard procedures. The results demonstrated that metformin activated AMPK and decreased phosphorylation of Akt and Erk. Furthermore, combinations of metformin with either Akt or Erk inhibitors synergistically diminished cancer proliferation, suggesting the involvement of Akt- and Erk- related pathways. Intravesical metformin 26 and 104 mg/kg, twice per week demonstrated a rapid elimination of the implanted tumor without any evidence of toxicity. In contrast, oral treatment at a dose of 800mg/kg/d exhibited little efficacy whereas severe toxicity existed if the dosage is higher. Collectively, intravesical metformin displays potent inhibition on bladder cancer in vitro and this preclinical study reveals the profound therapeutic application of metformin with durable tolerance via intravesical administration route. PMID- 26802023 TI - ALK and ROS1 as targeted therapy paradigms and clinical implications to overcome crizotinib resistance. AB - During the past decade, more than 10 targetable oncogenic driver genes have been validated in non-small cell lung cancer (NSCLC). Anaplastic lymphoma kinase (ALK) and ROS1 kinase are two new driver genes implicated in ALK- and ROS1-rearranged NSCLC. Inhibition of ALK and ROS1 by crizotinib has been reported to be highly effective and well tolerated in these patients. However, resistance to crizotinib emerges years after treatment, and increasing efforts have been made to overcome this issue. Here, we review the biology of ALK and ROS1 and their roles in cancer progression. We also summarize the ongoing and completed clinical trials validating ALK and ROS1 as targets for cancer treatment. In the last section of the review, we will discuss the molecular mechanisms of crizotinib resistance and focus approaches to overcome it. This review describes an exciting new area of research and may provide new insights for targeted cancer therapies. PMID- 26802024 TI - The second European interdisciplinary Ewing sarcoma research summit--A joint effort to deconstructing the multiple layers of a complex disease. AB - Despite multimodal treatment, long term outcome for patients with Ewing sarcoma is still poor. The second "European interdisciplinary Ewing sarcoma research summit" assembled a large group of scientific experts in the field to discuss their latest unpublished findings on the way to the identification of novel therapeutic targets and strategies. Ewing sarcoma is characterized by a quiet genome with presence of an EWSR1-ETS gene rearrangement as the only and defining genetic aberration. RNA-sequencing of recently described Ewing-like sarcomas with variant translocations identified them as biologically distinct diseases. Various presentations adressed mechanisms of EWS-ETS fusion protein activities with a focus on EWS-FLI1. Data were presented shedding light on the molecular underpinnings of genetic permissiveness to this disease uncovering interaction of EWS-FLI1 with recently discovered susceptibility loci. Epigenetic context as a consequence of the interaction between the oncoprotein, cell type, developmental stage, and tissue microenvironment emerged as dominant theme in the discussion of the molecular pathogenesis and inter- and intra-tumor heterogeneity of Ewing sarcoma, and the difficulty to generate animal models faithfully recapitulating the human disease. The problem of preclinical development of biologically targeted therapeutics was discussed and promising perspectives were offered from the study of novel in vitro models. Finally, it was concluded that in order to facilitate rapid pre-clinical and clinical development of novel therapies in Ewing sarcoma, the community needs a platform to maintain knowledge of unpublished results, systems and models used in drug testing and to continue the open dialogue initiated at the first two Ewing sarcoma summits. PMID- 26802025 TI - Anti-ovarian tumor response of donor peripheral blood mononuclear cells is due to infiltrating cytotoxic NK cells. AB - Treatment of ovarian cancer, a leading cause of gynecological malignancy, has good initial efficacy with surgery and platinum/taxane-based chemotherapy, but poor long-term survival in patients. Inferior long-term prognosis is attributed to intraperitoneal spreading, relapse and ineffective alternate therapies. Adoptive cell therapy is promising for tumor remission, although logistical concerns impede widespread implementation. In this study, healthy PBMCs were used to examine the immune response in a mouse model with human ovarian cancer, where natural killer (NK) cells were found to be the effector cells that elicited an anti-tumor response. Presence of tumor was found to stimulate NK cell expansion in mice treated intraperitoneally with PBMC+Interleukin-2 (IL-2), as compared to no expansion in non-tumor-bearing mice given the same treatment. PBMC+IL-2 treated mice exhibiting NK cell expansion had complete tumor remission. To validate NK cell mediated anti-tumor response, the intratumoral presence of NK cells and their cytotoxicity was confirmed by immunohistochemistry and granzyme activity of NK cells recovered from the tumor. Collectively, this study highlights the significance of NK cell-cytotoxic response to tumor, which may be attributed to interacting immune cell types in the PBMC population, as opposed to clinically used isolated NK cells showing lack of anti-tumor efficacy in ovarian cancer patients. PMID- 26802028 TI - XIAP-associating factor 1, a transcriptional target of BRD7, contributes to endothelial cell senescence. AB - X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is well known as an antagonist of XIAP-mediated caspase inhibition. Although XAF1 serves as a tumor-suppressor gene, the role of XAF1 in cellular senescence remains unclear. We found that XAF1 expression was increased by genotoxic agents, such as doxorubicin and ionizing radiation in pulmonary microvascular endothelial cells, consequently leading to premature senescence. Conversely, downregulation of XAF1 in premature senescent cells partially overcame endothelial cell senescence. p53 knockdown, but not p16 knockdown, abolished senescence phenotypes caused by XAF1 induction. XAF1 expression was transcriptionally regulated by Bromodomain 7 (BRD7). XAF1 induction with interferon-gamma (IFN-gamma) treatment was abrogated by BRD7 knockdown, which resulted in blocking interferon-induced senescence. In lung cancer cells, XAF1 tumor suppressor activity was decreased by BRD7 knockdown, and inhibition of tumor growth by IFN-gamma did not appear in BRD7 depleted xenograft tumors. These data suggest that XAF1 is involved in BRD7 associated senescence and plays an important role in the regulation of endothelial senescence through a p53-dependent pathway. Furthermore, regulation of the BRD7/XAF1 system might contribute to tissue or organismal aging and protection against cellular transformation. PMID- 26802027 TI - Chromosomal anomalies at 1q, 3, 16q, and mutations of SIX1 and DROSHA genes underlie Wilms tumor recurrences. AB - Approximately half of children suffering from recurrent Wilms tumor (WT) develop resistance to salvage therapies. Hence the importance to disclose events driving tumor progression/recurrence. Future therapeutic trials, conducted in the setting of relapsing patients, will need to prioritize targets present in the recurrent lesions. Different studies identified primary tumor-specific signatures associated with poor prognosis. However, given the difficulty in recruiting specimens from recurrent WTs, little work has been done to compare the molecular profile of paired primary/recurrent diseases. We studied the genomic profile of a cohort of eight pairs of primary/recurrent WTs through whole-genome SNP arrays, and investigated known WT-associated genes, including SIX1, SIX2 and micro RNA processor genes, whose mutations have been recently proposed as associated with worse outcome. Through this approach, we sought to uncover anomalies characterizing tumor recurrence, either acquired de novo or already present in the primary disease, and to investigate whether they overlapped with known molecular prognostic signatures. Among the aberrations that we disclosed as potentially acquired de novo in recurrences, some had been already recognized in primary tumors as associated with a higher risk of relapse. These included allelic imbalances of chromosome 1q and of chromosome 3, and CN losses on chromosome 16q. In addition, we found that SIX1 and DROSHA mutations can be heterogeneous events (both spatially and temporally) within primary tumors, and that their co-occurrence might be positively selected in the progression to recurrent disease. Overall, these results provide new insights into genomic and genetic events underlying WT progression/recurrence. PMID- 26802026 TI - BRAF associated autophagy exploitation: BRAF and autophagy inhibitors synergise to efficiently overcome resistance of BRAF mutant colorectal cancer cells. AB - Autophagy is the basic catabolic mechanism that involves cell degradation of unnecessary or dysfunctional cellular components. Autophagy has a controversial role in cancer--both in protecting against tumor progression by isolation of damaged organelles, or by potentially contributing to cancer growth. The impact of autophagy in RAS induced transformation still remains to be further analyzed based on the differential effect of RAS isoforms and tumor cell context. In the present study, the effect of KRAS/BRAF/PIK3CA oncogenic pathways on the autophagic cell properties and on main components of the autophagic machinery like p62 (SQSTM1), Beclin-1 (BECN1) and MAP1LC3 (LC3) in colon cancer cells was investigated. This study provides evidence that BRAF oncogene induces the expression of key autophagic markers, like LC3 and BECN1 in colorectal tumor cells. Herein, PI3K/AKT/MTOR inhibitors induce autophagic tumor properties, whereas RAF/MEK/ERK signalling inhibitors reduce expression of autophagic markers. Based on the ineffectiveness of BRAFV600E inhibitors in BRAFV600E bearing colorectal tumors, the BRAF related autophagic properties in colorectal cancer cells are further exploited, by novel combinatorial anti-cancer protocols. Strong evidence is provided here that pre-treatment of autophagy inhibitor 3-MA followed by its combination with BRAFV600E targeting drug PLX4720 can synergistically sensitize resistant colorectal tumors. Notably, colorectal cancer cells are very sensitive to mono-treatments of another autophagy inhibitor, Bafilomycin A1. The findings of this study are expected to provide novel efficient protocols for treatment of otherwise resistant colorectal tumors bearing BRAFV600E, by exploiting the autophagic properties induced by BRAF oncogene. PMID- 26802029 TI - Imprinting defects at human 14q32 locus alters gene expression and is associated with the pathobiology of osteosarcoma. AB - Osteosarcoma is the most common primary bone malignancy affecting children and adolescents. Although several genetic predisposing conditions have been associated with osteosarcoma, our understanding of its pathobiology is rather limited. Here we show that, first, an imprinting defect at human 14q32-locus is highly prevalent (87%) and specifically associated with osteosarcoma patients < 30 years of age. Second, the average demethylation at differentially methylated regions (DMRs) in the 14q32-locus varied significantly compared to genome-wide demethylation. Third, the 14q32-locus was enriched in both H3K4-me3 and H3K27-me3 histone modifications that affected expression of all imprinted genes and miRNAs in this region. Fourth, imprinting defects at 14q32 - DMRs are present in triad DNA samples from affected children and their biological parents. Finally, imprinting defects at 14q32-DMRs were also observed at higher frequencies in an Rb1/Trp53 mutation-induced osteosarcoma mouse model. Further analysis of normal and tumor tissues from a Sleeping Beauty mouse model of spontaneous osteosarcoma supported the notion that these imprinting defects may be a key factor in osteosarcoma pathobiology. In conclusion, we demonstrate that imprinting defects at the 14q32 locus significantly alter gene expression, may contribute to the pathogenesis of osteosarcoma, and could be predictive of survival outcomes. PMID- 26802030 TI - Ion Mobility Spectrometry-Hydrogen Deuterium Exchange Mass Spectrometry of Anions: Part 2. Assessing Charge Site Location and Isotope Scrambling. AB - Ion mobility spectrometry (IMS) coupled with gas-phase hydrogen deuterium exchange (HDX)-mass spectrometry (MS) and molecular dynamic simulations (MDS) has been used for structural investigation of anions produced by electrospraying a sample containing a synthetic peptide having the sequence KKDDDDDIIKIIK. In these experiments the potential of the analytical method for locating charge sites on ions as well as for utilizing collision-induced dissociation (CID) to reveal the degree of deuterium uptake within specific amino acid residues has been assessed. For diffuse (i.e., more elongated) [M - 2H](2-) ions, decreased deuterium content along with MDS data suggest that the D4 and D6 residues are charge sites, whereas for the more diffuse [M - 3H](3-) ions, the data suggest that the D4, D7, and the C-terminus are deprotonated. Fragmentation of mobility-selected, diffuse [M - 2H](2-) ions to determine deuterium uptake at individual amino acid residues reveals a degree of deuterium retention at incorporation sites. Although the diffuse [M - 3H](3-) ions may show more HD scrambling, it is not possible to clearly distinguish HD scrambling from the expected deuterium uptake based on a hydrogen accessibility model. The capability of the IMS-HDX-MS/MS approach to provide relevant details about ion structure is discussed. Additionally, the ability to extend the approach for locating protonation sites on positively charged ions is presented. PMID- 26802031 TI - Editorial. PMID- 26802032 TI - First report of otitis externa caused by Schizophyllum commune and review of the literature. AB - Basidiomycete Schizophyllum commune is a widely distributed cellulolytic fungus that is a well-known pathogen. It can cause a wide range of different infections, and here we describe the first case of otitis externa and a molecularly based identification process. PMID- 26802033 TI - [Not Available]. PMID- 26802034 TI - Professional internet information source used as educational resource for patients with insulin-treated diabetes in the Czech Republic: a 5-year analysis of operations. PMID- 26802035 TI - Prediction of regression of retinal neovascularisation after panretinal photocoagulation for proliferative diabetic retinopathy. AB - PURPOSE: The purpose of this study was to evaluate the regression of neovascularization elsewhere (NVE) after panretinal photocoagulation (PRP) based on its location in relation to the internal limiting membrane (ILM). METHODS: Participants in this retrospective case series were 47 patients with active NVE within the vascular arcade. All patients were treated with PRP and followed up for at least 12 months. The time to regression of NVE based on its location relative to the ILM on spectral domain-optical coherence tomography (SD-OCT) was analyzed. RESULTS: The proportion of eyes, showing regression of NVE at the end of follow-up period was 19/25 (76 %) in the "below ILM" group and 13/22 (59 %) in the "above ILM" group. The "below ILM" group was associated with a twofold enhanced regression of NVE in comparison to the "above ILM" group (HR = 2.13, p = 0.038). CONCLUSIONS: Regression of NVE is determined by its location relative to the ILM. Patients with "below ILM" NVE were found to show a twofold increased regression rate in comparison with the "above ILM" group, while the proportion of eyes showing regression of NVE at the end of the follow-up period was significantly greater in the "below ILM" than the "above ILM" group. PMID- 26802036 TI - A survey of patient satisfaction with use of microwave device for axillary hyperhidrosis. PMID- 26802037 TI - Primary immunodeficiencies worldwide: an updated overview from the Jeffrey Modell Centers Global Network. AB - Primary immunodeficiencies (PI) are defects of the immune system that cause severe, sometimes life-threatening, infections if not diagnosed and treated appropriately. Many patients with PI are undiagnosed, under-diagnosed, or misdiagnosed. To raise awareness and assure earliest diagnosis, appropriate treatment, and proper care management, the Jeffrey Modell Foundation (JMF) implemented a physician education and public awareness program beginning in 2003. Data are requested annually from physician experts within the Jeffrey Modell Centers Network (JMCN), consisting of 602 expert physicians, at 253 academic institutions, in 206 cities, and 84 countries spanning six continents. Center Directors reported on patients' specific PI defects and treatment modalities including immunoglobulins, transplantation, and gene therapy as well as data on gender and age. Center Directors also provided physician-reported patient outcomes as well as pre- and post-diagnosis differences. Costs were assigned to these factors. In collaboration with the Network, JMF advocated, funded, and implemented population-based newborn screening for severe combined immunodeficiency and T cell lymphopenia, covering 96.2 % of all newborns in the US. Finally, 21 JMF Centers participated in a polio surveillance study of patients with PI who either received or have been exposed to the oral polio vaccine. These initiatives have led to an overall better understanding of the immune system and will continue to improve quality of life for those with PI. PMID- 26802040 TI - RETRACTION. PMID- 26802039 TI - TEMPRANILLO Reveals the Mesophyll as Crucial for Epidermal Trichome Formation. AB - Plant trichomes are defensive specialized epidermal cells. In all accepted models, the epidermis is the layer involved in trichome formation, a process controlled by gibberellins (GAs) in Arabidopsis rosette leaves. Indeed, GA activates a genetic cascade in the epidermis for trichome initiation. Here we report that TEMPRANILLO (TEM) genes negatively control trichome initiation not only from the epidermis but also from the leaf layer underneath the epidermis, the mesophyll. Plants over-expressing or reducing TEM specifically in the mesophyll, display lower or higher trichome numbers, respectively. We surprisingly found that fluorescently labeled GA3 accumulates exclusively in the mesophyll of leaves, but not in the epidermis, and that TEM reduces its accumulation and the expression of several newly identified GA transporters. This strongly suggests that TEM plays an essential role, not only in GA biosynthesis, but also in regulating GA distribution in the mesophyll, which in turn directs epidermal trichome formation. Moreover, we show that TEM also acts as a link between GA and cytokinin signaling in the epidermis by negatively regulating downstream genes of both trichome formation pathways. Overall, these results call for a re-evaluation of the present theories of trichome formation as they reveal mesophyll essential during epidermal trichome initiation. PMID- 26802038 TI - Tonoplast Aquaporins Facilitate Lateral Root Emergence. AB - Aquaporins (AQPs) are water channels allowing fast and passive diffusion of water across cell membranes. It was hypothesized that AQPs contribute to cell elongation processes by allowing water influx across the plasma membrane and the tonoplast to maintain adequate turgor pressure. Here, we report that, in Arabidopsis (Arabidopsis thaliana), the highly abundant tonoplast AQP isoforms AtTIP1;1, AtTIP1;2, and AtTIP2;1 facilitate the emergence of new lateral root primordia (LRPs). The number of lateral roots was strongly reduced in the triple tip mutant, whereas the single, double, and triple tip mutants showed no or minor reduction in growth of the main root. This phenotype was due to the retardation of LRP emergence. Live cell imaging revealed that tight spatiotemporal control of TIP abundance in the tonoplast of the different LRP cells is pivotal to mediating this developmental process. While lateral root emergence is correlated to a reduction of AtTIP1;1 and AtTIP1;2 protein levels in LRPs, expression of AtTIP2;1 is specifically needed in a restricted cell population at the base, then later at the flanks, of developing LRPs. Interestingly, the LRP emergence phenotype of the triple tip mutants could be fully rescued by expressing AtTIP2;1 under its native promoter. We conclude that TIP isoforms allow the spatial and temporal fine tuning of cellular water transport, which is critically required during the highly regulated process of LRP morphogenesis and emergence. PMID- 26802042 TI - Heat-shock-induced refolding entails rapid degradation of bsrG toxin mRNA by RNases Y and J1. AB - Gene regulation accomplished by alternative folding of an mRNA is a widely used mechanism. Classical examples are the various transcriptional attenuation mechanisms that employ, for example, leader peptide translation, or binding of a modified protein, an uncharged tRNA or an antisense RNA to the 5' untranslated region of an mRNA. With the discovery of transcriptional and translational riboswitches, it became clear that small metabolites or even metal ions can also alter RNA secondary structures and, hence, gene expression. In addition, biophysical factors like temperature can affect RNA folding, as exemplified by RNA thermometers. We have investigated in detail the type I toxin-antitoxin system bsrG/SR4 from Bacillus subtilis. The antitoxin SR4 is a cis-encoded regulatory RNA that neutralizes BsrG toxin action. SR4 prevents toxin expression by promoting degradation of the toxin mRNA and inhibiting its translation. In addition, upon temperature shock the amount of toxin mRNA decreases significantly. Here, we demonstrate that heat shock induces a refolding in the central region of the toxin mRNA that makes it more accessible to degradation by RNases Y and J1. Furthermore, we show that BsrG might play a role at the onset of stationary phase, when the antitoxin SR4 can no longer prevent toxin synthesis. PMID- 26802043 TI - Rejection Sensitivity, Jealousy, and the Relationship to Interpersonal Aggression. AB - The development and maintenance of interpersonal relationships lead individuals to risk rejection in the pursuit of acceptance. Some individuals are predisposed to experience a hypersensitivity to rejection that is hypothesized to be related to jealous and aggressive reactions within interpersonal relationships. The current study used convenience sampling to recruit 247 young adults to evaluate the relationship between rejection sensitivity, jealousy, and aggression. A mediation model was used to test three hypotheses: Higher scores of rejection sensitivity would be positively correlated to higher scores of aggression (Hypothesis 1); higher scores of rejection sensitivity would be positively correlated to higher scores of jealousy (Hypothesis 2); jealousy would mediate the relationship between rejection sensitivity and aggression (Hypothesis 3). Study results suggest a tendency for individuals with high rejection sensitivity to experience higher levels of jealousy, and subsequently have a greater propensity for aggression, than individuals with low rejection sensitivity. Future research that substantiates a link between hypersensitivity to rejection, jealousy, and aggression may provide an avenue for prevention, education, or intervention in reducing aggression within interpersonal relationships. PMID- 26802041 TI - Water Deficit Enhances C Export to the Roots in Arabidopsis thaliana Plants with Contribution of Sucrose Transporters in Both Shoot and Roots. AB - Root high plasticity is an adaptation to its changing environment. Water deficit impairs growth, leading to sugar accumulation in leaves, part of which could be available to roots via sucrose (Suc) phloem transport. Phloem loading is widely described in Arabidopsis (Arabidopsis thaliana), while unloading in roots is less understood. To gain information on leaf-to-root transport, a soil-based culture system was developed to monitor root system architecture in two dimensions. Under water deficit (50% of soil water-holding capacity), total root length was strongly reduced but the depth of root foraging and the shape of the root system were less affected, likely to improve water uptake. (14)CO2 pulse-chase experiments confirmed that water deficit enhanced carbon (C) export to the roots, as suggested by the increased root-to-shoot ratio. The transcript levels of AtSWEET11 (for sugar will eventually be exported transporter), AtSWEET12, and AtSUC2 (for Suc carrier) genes, all three involved in Suc phloem loading, were significantly up-regulated in leaves of water deficit plants, in accordance with the increase in C export from the leaves to the roots. Interestingly, the transcript levels of AtSUC2 and AtSWEET11 to AtSWEET15 were also significantly higher in stressed roots, underlying the importance of Suc apoplastic unloading in Arabidopsis roots and a putative role for these Suc transporters in Suc unloading. These data demonstrate that, during water deficit, plants respond to growth limitation by allocating relatively more C to the roots to maintain an efficient root system and that a subset of Suc transporters is potentially involved in the flux of C to and in the roots. PMID- 26802044 TI - Perpetration and Victimization of Intimate Partner Violence Among Young Men and Women in Dar es Salaam, Tanzania. AB - We describe and compare the baseline rates of victimization and perpetration of three forms of intimate partner violence (IPV)-psychological, physical, and sexual-among sexually active men ( n = 1,113) and women ( n = 226) enrolled in an ongoing cluster-randomized HIV and gender-based violence prevention trial in Dar es Salaam, Tanzania. IPV was measured using a modified version of the World Health Organization Violence Against Women instrument. We assess the degree to which men and women report overlapping forms of IPV victimization and perpetration. Sociodemographic and other factors associated with increased risk of victimization and perpetration of IPV are examined. Within the last 12 months, 34.8% of men and 35.8% of women reported any form of IPV victimization. Men were more likely than women to report perpetrating IPV (27.6% vs. 14.6%, respectively). We also found high rates of co-occurrence of IPV victimization and perpetration with 69.7% of male perpetrators and 81.8% of female perpetrators also reporting victimization during the last year. Among men, having ever consumed alcohol and experiencing childhood violence were associated with increased risk of most forms of IPV. Younger women were more likely to report perpetrating IPV than older women. We found evidence of gender symmetry with regard to most forms of IPV victimization, but men reported higher rates of IPV perpetration than women. Given the substantial overlap between victimization and perpetration reported, our findings suggest that IPV may be bidirectional within relationships in this setting and warrant further investigation. Implications for interventions are discussed. PMID- 26802045 TI - Factors Associated With Women's Reporting of Intimate Partner Violence in Spain. AB - In Spain, in 2013, the 20% of women who were murdered by their partner had reported him previously. We analyze the 2011 Spanish-Macrosurvey on Gender Violence to identify and analyze the prevalence of and the principal factors associated with reporting a situation of intimate partner violence (IPV) and the main reasons women cite for not filing such reports, or for subsequently deciding to withdraw their complaint. Overall, 72.8% of women exposed to IPV did not report their aggressor. The most frequent reasons for not reporting were not giving importance to the situation (33.9%), and fear and lack of trust in the reporting process (21.3%). The main reasons for withdrawing the complaint were cessation of the violence (20.0%), and fear and threats (18.2%). The probability of reporting increased among women with young children who were abused, prevalence ratio (95% confidence interval [CI]): 2.14 [1.54, 2.98], and those whose mother was abused, prevalence ratio (95% CI): 2.25 [1.42, 3.57]. Always focusing on the need to protect women who report abuse, it is necessary to promote the availability of and access to legal resources especially among women who use them less: women who do not have children and women who do not have previous family exposure to violence. PMID- 26802047 TI - Husband's Alcohol Use, Intimate Partner Violence, and Family Maltreatment of Low Income Postpartum Women in Mumbai, India. AB - Husbands' alcohol use has been associated with family-level stress and intimate partner violence (IPV) against women in India. Joint family systems are common in India and IPV often co-occurs with non-violent family maltreatment of wives (e.g., nutritional deprivation, deprivation of sleep, blocking access to health care). Alcohol use increases for some parents following the birth of a child. This study examined 1,038 postpartum women's reports of their husbands' alcohol use and their own experiences of IPV (by husband) and non-violent maltreatment from husbands and/or in-laws. We analyzed cross-sectional, quantitative data collected in 2008, from women (ages 15-35) seeking immunizations for their infants <6 months at three large urban health centers in Mumbai, India. Crude and adjusted logistic regression models estimated associations between the independent variable (husbands' past month use of alcohol) and two dependent variables (postpartum IPV and maltreatment). Overall, 15% of husbands used alcohol, ranging from daily drinkers (10%) to those who drank one to two times per week (54%). Prevalence of postpartum IPV and family maltreatment was 18% and 42%, respectively. Prevalence of IPV among women married to alcohol users was 27%. Most abused women's husbands always (27%) or sometimes (37%) drank during violent episodes. Risk for IPV increased with a man's increasing frequency of consumption. Women who lived with a husband who drank alcohol, relative to non drinkers, were more likely to report postpartum IPV, aOR = 2.0, 95% confidence interval (CI) = [1.3, 3.1]. Husbands' drinking was marginally associated with increased risk for family maltreatment, aOR = 1.4, 95% CI = [1.0, 2.1]. Our findings suggest that men's alcohol use is an important risk factor for postpartum IPV and maltreatment. Targeted services for Indian women contending with these issues are implicated. Postpartum care offers an ideal opportunity to screen for IPV, household maltreatment, and other health risks, such as husband's use of alcohol. There is need to scale up proven successful interventions for reducing men's alcohol use and design strategies that provide at-risk women protection from alcohol-related IPV. PMID- 26802046 TI - The Association Between Military Sexual Trauma and Use of VA and Non-VA Health Care Services Among Female Veterans With Military Service in Iraq or Afghanistan. AB - Military sexual trauma (MST) has been linked with increased rates of mental health disorders among veterans. Few studies have addressed how MST is related to use of VA and non-VA health care. The purpose of the current study was to (a) examine the association between MST, combat experiences, and mental health outcomes (i.e., posttraumatic stress disorder [PTSD] and depression) and (b) examine the association of MST and use of VA and non-VA health care services among female veterans who served in Iraq and Afghanistan. Female respondents to a survey assessing Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) veterans' needs and health ( N = 185) completed measures of demographic variables, military history, combat exposure, MST, PTSD, and depression symptoms, and use of VA and non-VA health care. Overall, 70% of the sample experienced one or more combat-related experiences and 15.7% endorsed MST during deployment to Iraq or Afghanistan. MST and combat exposure were both positively associated with PTSD and depression symptoms even after controlling for the effects of demographic and military history variables. MST was associated with increased use of VA mental health services in bivariate results but was not independently related to VA service utilization after accounting for PTSD and depression symptoms. Approximately half of the women who reported MST had not used VA health care. Continued outreach and education initiatives may be needed to ensure veterans understand the resources available to address MST-related mental and physical health problems through the VA. PMID- 26802048 TI - epsilon-globin expression is regulated by SUV4-20h1. PMID- 26802049 TI - Helicase-like transcription factor is a RUNX1 target whose downregulation promotes genomic instability and correlates with complex cytogenetic features in acute myeloid leukemia. AB - Helicase-like transcription factor is a SWI/SNF chromatin remodeling factor involved in various biological processes. However, little is known about its role in hematopoiesis. In this study, we measured helicase-like transcription factor mRNA expression in the bone marrow of 204 adult patients with de novo acute myeloid leukemia. Patients were dichotomized into low and high expression groups at the median level for clinicopathological correlations. Helicase-like transcription factor levels were dramatically reduced in the low expression patient group compared to those in the normal controls (n=40) (P<0.0001). Low helicase-like transcription factor expression correlated positively with French American-British M4/M5 subtypes (P<0.0001) and complex cytogenetic abnormalities (P=0.02 for >=3 abnormalities;P=0.004 for >=5 abnormalities) but negatively with CEBPA double mutations (P=0.012). Also, low expression correlated with poorer overall (P=0.005) and event-free (P=0.006) survival in the intermediate-risk cytogenetic subgroup. Consistent with the more aggressive disease associated with low expression, helicase-like transcription factor knockdown in leukemic cells promoted proliferation and chromosomal instability that was accompanied by downregulation of mitotic regulators and impaired DNA damage response. The significance of helicase-like transcription factor in genome maintenance was further indicated by its markedly elevated expression in normal human CD34(+)hematopoietic stem cells. We further demonstrated that helicase-like transcription factor was a RUNX1 target and transcriptionally repressed by RUNX1 ETO and site-specific DNA methylation through a duplicated RUNX1 binding site in its promoter. Taken together, our findings provide new mechanistic insights on genomic instability linked to helicase-like transcription factor deregulation, and strongly suggest a tumor suppressor function of the SWI/SNF protein in acute myeloid leukemia. PMID- 26802050 TI - Impaired killing of Candida albicans by granulocytes mobilized for transfusion purposes: a role for granule components. AB - Granulocyte transfusions are used to treat neutropenic patients with life threatening bacterial or fungal infections that do not respond to anti-microbial drugs. Donor neutrophils that have been mobilized with granulocyte-colony stimulating factor (G-CSF) and dexamethasone are functional in terms of antibacterial activity, but less is known about their fungal killing capacity. We investigated the neutrophil-mediated cytotoxic response against C. albicans and A. fumigatus in detail. Whereas G-CSF/dexamethasone-mobilized neutrophils appeared less mature as compared to neutrophils from untreated controls, these cells exhibited normal ROS production by the NADPH oxidase system and an unaltered granule mobilization capacity upon stimulation. G-CSF/dexamethasone mobilized neutrophils efficiently inhibited A. fumigatus germination and killed Aspergillus and Candida hyphae, but the killing of C. albicans yeasts was distinctly impaired. Following normal Candida phagocytosis, analysis by mass spectrometry of purified phagosomes after fusion with granules demonstrated that major constituents of the antimicrobial granule components, including major basic protein (MBP), were reduced. Purified MBP showed candidacidal activity, and neutrophil-like Crisp-Cas9 NB4-KO-MBP differentiated into phagocytes were impaired in Candida killing. Together, these findings indicate that G CSF/dexamethasone-mobilized neutrophils for transfusion purposes have a selectively impaired capacity to kill Candida yeasts, as a consequence of an altered neutrophil granular content. PMID- 26802051 TI - Extracellular vesicle miR-7977 is involved in hematopoietic dysfunction of mesenchymal stromal cells via poly(rC) binding protein 1 reduction in myeloid neoplasms. AB - The failure of normal hematopoiesis is observed in myeloid neoplasms. However, the precise mechanisms governing the replacement of normal hematopoietic stem cells in their niche by myeloid neoplasm stem cells have not yet been clarified. Primary acute myeloid leukemia and myelodysplastic syndrome cells induced aberrant expression of multiple hematopoietic factors including Jagged-1, stem cell factor and angiopoietin-1 in mesenchymal stem cells even in non-contact conditions, and this abnormality was reverted by extracellular vesicle inhibition. Importantly, the transfer of myeloid neoplasm-derived extracellular vesicles reduced the hematopoietic supportive capacity of mesenchymal stem cells. Analysis of extracellular vesicle microRNA indicated that several species, including miR-7977 from acute myeloid leukemia cells, were higher than those from normal CD34(+)cells. Remarkably, the copy number of miR-7977 in bone marrow interstitial fluid was elevated not only in acute myeloid leukemia, but also in myelodysplastic syndrome, as compared with lymphoma without bone marrow localization. The transfection of the miR-7977 mimic reduced the expression of the posttranscriptional regulator, poly(rC) binding protein 1, in mesenchymal stem cells. Moreover, the miR-7977 mimic induced aberrant reduction of hematopoietic growth factors in mesenchymal stem cells, resulting in decreased hematopoietic-supporting capacity of bone marrow CD34(+)cells. Furthermore, the reduction of hematopoietic growth factors including Jagged-1, stem cell factor and angiopoietin-1 were reverted by target protection of poly(rC) binding protein 1, suggesting that poly(rC) binding protein 1 could be involved in the stabilization of several growth factors. Thus, miR-7977 in extracellular vesicles may be a critical factor that induces failure of normal hematopoiesis via poly(rC) binding protein 1 suppression. PMID- 26802052 TI - The role of Matriptase-2 during the early postnatal development in humans. PMID- 26802054 TI - Multi-state analysis illustrates treatment success after stem cell transplantation for acute myeloid leukemia followed by donor lymphocyte infusion. AB - In the field of hematopoietic stem cell transplantation, the common approach is to focus outcome analyses on time to relapse and death, without assessing the impact of post-transplant interventions. We investigated whether a multi-state model would give insight into the events after transplantation in a cohort of patients who were transplanted using a strategy including scheduled donor lymphocyte infusions. Seventy-eight consecutive patients who underwent myeloablative T-cell depleted allogeneic stem cell transplantation for acute myeloid leukemia or myelodysplastic syndrome were studied. We constructed a multi state model to analyze the impact of donor lymphocyte infusion and graft-versus host disease on the probabilities of relapse and non-relapse mortality over time. Based on this model we introduced a new measure for outcome after transplantation which we called 'treatment success': being alive without relapse and immunosuppression for graft-versus-host disease. All relevant clinical events were implemented into the multi-state model and were denoted treatment success or failure (either transient or permanent). Both relapse and non-relapse mortality were causes of failure of comparable magnitude. Whereas relapse was the dominant cause of failure from the transplantation state, its rate was reduced after graft versus-host disease, and especially after donor lymphocyte infusion. The long term probability of treatment success was approximately 40%. This probability was increased after donor lymphocyte infusion. Our multi-state model helps to interpret the impact of post-transplantation interventions and clinical events on failure and treatment success, thus extracting more information from observational data. PMID- 26802055 TI - Demonstrating junior doctors ask Jeremy Hunt to stop misusing statistics. PMID- 26802053 TI - Expression of a dominant T-cell receptor can reduce toxicity and enhance tumor protection of allogeneic T-cell therapy. AB - Due to the lack of specificity for tumor antigens, allogeneic T-cell therapy is associated with graft-versus-host disease. Enhancing the anti-tumor specificity while reducing the graft-versus-host disease risk of allogeneic T cells has remained a research focus. In this study, we demonstrate that the introduction of 'dominant' T-cell receptors into primary murine T cells can suppress the expression of endogenous T-cell receptors in a large proportion of the gene modified T cells. Adoptive transfer of allogeneic T cells expressing a 'dominant' T-cell receptor significantly reduced the graft-versus-host toxicity in recipient mice. Using two bone marrow transplant models, enhanced anti-tumor activity was observed in the presence of reduced graft-versus-host disease. However, although transfer of T-cell receptor gene-modified allogeneic T cells resulted in the elimination of antigen-positive tumor cells and improved the survival of treated mice, it was associated with accumulation of T cells expressing endogenous T-cell receptors and the development of delayed graft-versus-host disease. The in-vivo deletion of the engineered T cells, mediated by endogenous mouse mammary tumor virus MTV8 and MTV9, abolished graft-versus-host disease while retaining significant anti-tumor activity of adoptively transferred T cells. Together, this study shows that the in-vitro selection of allogeneic T cells expressing high levels of a 'dominant' T-cell receptor can lower acute graft-versus-host disease and enhance anti-tumor activity of adoptive cell therapy, while the in-vivo outgrowth of T cells expressing endogenous T-cell receptors remains a risk factor for the delayed onset of graft-versus-host disease. PMID- 26802056 TI - A Vascular Malformation Invading the Medial Plantar Nerve. PMID- 26802057 TI - A Century of Excellence: Celebrating 100 Years of The Journal of Immunology. PMID- 26802058 TI - The Secrets of the Class II MHC Peptidome Start To Be Revealed. PMID- 26802059 TI - Pillars Article: Sequence Analysis of Peptides Bound to MHC Class II Molecules. Nature. 1991. 353: 622-627. PMID- 26802060 TI - The Expanding Spectrum of Ligands for Leukocyte Ig-like Receptors. AB - The human leukocyte Ig-like receptor family is part of the paired receptor system. The receptors are widely expressed by various immune cells, and new functions continue to emerge. Understanding the range of functions of the receptors is of general interest because several types of pathogens exploit the receptors and genetic diversity of the receptors has been linked to various autoimmune diseases. Class I major histocompatibility molecules were the first ligands appreciated for these receptors, but the types of ligands identified over the last several years are quite diverse, including intact pathogens, immune modulatory proteins, and molecules normally found within the CNS. This review focuses on the types of ligands described to date, how the individual receptors bind to several distinct types of ligands, and the known functional consequences of those interactions. PMID- 26802062 TI - Correction. PMID- 26802061 TI - Reassessing the Evolutionary Importance of Inflammasomes. AB - Inflammasomes monitor the cytosol for microbial contamination or perturbation and, thus, are predicted to provide potent defense against infection. However, the compendium of data from murine infection models suggests that inflammasomes merely delay the course of disease, allowing the host time to mount an adaptive response. Interpretations of such results are confounded by inflammasome-evasion strategies of vertebrate-adapted pathogens. Conversely, environmental opportunistic pathogens have not evolved in the context of inflammasomes and, therefore, are less likely to evade them. Indeed, opportunistic pathogens do not normally cause disease in wild-type animals. Accordantly, the extreme virulence of two opportunistic bacterial pathogens, Burkholderia thailandensis and Chromobacterium violaceum, is fully counteracted by inflammasomes in murine models. This leads us to propose a new hypothesis: perhaps animals maintain inflammasomes over evolutionary time not to defend against vertebrate-adapted pathogens but instead to counteract infection by a plethora of undiscovered opportunistic pathogens residing in the environment. PMID- 26802063 TI - Autolytic recanalisation of a thrombotic artery. AB - This case describes a patient who presented with an occluded and ectatic right coronary artery. Initial aspiration and, later, guide catheter thrombectomy, liberated large volumes of thrombus but did not appear to restore significant flow. Thrombolysis in myocardial infarction (TIMI) 3 flow was, however, evident 2 weeks later, demonstrating the combined effect of vigorous thrombectomy and autolysis on a heavily thrombotic section of coronary artery. PMID- 26802064 TI - Role of fine needle aspiration cytology in the differential diagnosis of vascular anomalies from other lesions in the head and neck region. AB - Objective To summarise the role of fine needle aspiration cytology in the differential diagnosis of vascular anomalies from other lesions in the head and neck region by presenting five interesting cases reported from our hospital data. Method Five patients ranging in age from 3 months to 25 years old were diagnosed with vascular anomalies based on their histories, clinical examinations, imaging examinations and ultrasonic testing. The previous diagnosis of these patients were corrected by fine needle aspiration cytology in our hospital and the proper treatment was administered. Result Two cases were wrongly treated in a local hospital. All five of the patients underwent operations after excluding vascular anomalies by fine needle aspiration cytology. Conclusion Fine needle aspiration cytology should be used in the following situations to prevent misdiagnoses and the mistreatment as vascular anomalies: when imaging examination and ultrasonic testing lead to a diagnosis of vascular malformation, but the history or clinical examination does not confirm this diagnosis; when lesions are treated as "vascular malformations" by sclerotherapy, and the hydatid fluid is not like blood or lymph fluid; and when propranolol is used to treat the proliferation stage of "haemangiomas" with without any effect. PMID- 26802068 TI - Culture and Identification of Mouse Bone Marrow-Derived Dendritic Cells and Their Capability to Induce T Lymphocyte Proliferation. AB - BACKGROUND: The aim of this study was to establish a culture method for mouse dendritic cells (DCs) in vitro and observe their morphology at different growth stages and their ability to induce the proliferation of T lymphocytes. MATERIAL/METHODS: Granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) were used in combination to induce differentiation of mouse bone marrow (BM) mononucleocytes into DCs. The derived DCs were then assessed for morphology, phenotype, and function. RESULTS: The mouse BM-derived mononucleocytes had altered cell morphology 3 days after induction by GM-CSF and IL-4 and grew into colonies. Typical dendrites appeared 8 days after induction. Many mature DCs were generated, with typical dendritic morphology observed under scanning electron microscopy. Expression levels of CD11c, a specific marker of BM derived DCs, and of co-stimulatory molecules such as CD40, CD80, CD86, and MHC-II were elevated in the mature DCs. Furthermore, the mature DCs displayed a strong potency in stimulating the proliferation of syngenic or allogenic T lymphocytes. CONCLUSIONS: Mouse BM-derived mononucleocytes cultured in vitro can produce a large number of DCs, as well as immature DCs, in high purity. The described in vitro culture method lays a foundation for further investigations of anti-tumor vaccines. PMID- 26802069 TI - Nephrogenic systemic fibrosis: a serious adverse reaction to gadolinium - 1997 2006-2016. Part 1. PMID- 26802070 TI - Nephrogenic systemic fibrosis: a serious adverse reaction to gadolinium - 1997 2006-2016. Part 2. PMID- 26802072 TI - Pseudomonas putida KT2440 markerless gene deletion using a combination of lambda Red recombineering and Cre/loxP site-specific recombination. AB - Pseudomonas putida KT2440 is a saprophytic, environmental microorganism that plays important roles in the biodegradation of environmental toxic compounds and production of polymers, chemicals and secondary metabolites. Gene deletion of KT2440 usually involves cloning of the flanking homologous fragments of the gene of interest into a suicide vector followed by transferring into KT2440 via triparental conjugation. Selection and counterselection steps are then employed to generate gene deletion mutant. However, these methods are tedious and are not suitable for the manipulation of multiple genes simultaneously. Herein, a two step, markerless gene deletion method is presented. First, homologous armsflanked loxP-neo-loxP was knocked-in to replace the gene of interest, then the kanamycin resistance marker is removed by Cre recombinase catalyzed site-specific recombination. Both two-plasmid and one-plasmid gene systems were established. MekR/PmekA regulated gene expression system was found to be suitable for tight Cre expression in one-plasmid deletion system. The straightforward, time saving and highly efficient markerless gene deletion strategy has the potential to facilitate the genetics and functional genomics study of P. putida KT2440. PMID- 26802071 TI - Mercury resistance transposons in Bacilli strains from different geographical regions. AB - A total of 65 spore-forming mercury-resistant bacteria were isolated from natural environments worldwide in order to understand the acquisition of additional genes by and dissemination of mercury resistance transposons across related Bacilli genera by horizontal gene movement. PCR amplification using a single primer complementary to the inverted repeat sequence of TnMERI1-like transposons showed that 12 of 65 isolates had a transposon-like structure. There were four types of amplified fragments: Tn5084, Tn5085, Tn(d)MER3 (a newly identified deleted transposon-like fragment) and Tn6294 (a newly identified transposon). Tn(d)MER3 is a 3.5-kb sequence that carries a merRETPA operon with no merB or transposase genes. It is related to the mer operon of Bacillus licheniformis strain FA6-12 from Russia. DNA homology analysis shows that Tn6294 is an 8.5-kb sequence that is possibly derived from Tn(d)MER3 by integration of a TnMERI1-type transposase and resolvase genes and in addition the merR2 and merB1 genes. Bacteria harboring Tn6294 exhibited broad-spectrum mercury resistance to organomercurial compounds, although Tn6294 had only merB1 and did not have the merB2 and merB3 sequences for organomercurial lyases found in Tn5084 of B. cereus strain RC607. Strains with Tn6294 encode mercuric reductase (MerA) of less than 600 amino acids in length with a single N-terminal mercury-binding domain, whereas MerA encoded by strains MB1 and RC607 has two tandem domains. Thus, Tn(d)MER3 and Tn6294 are shorter prototypes for TnMERI1-like transposons. Identification of Tn6294 in Bacillus sp. from Taiwan and in Paenibacillus sp. from Antarctica indicates the wide horizontal dissemination of TnMERI1-like transposons across bacterial species and geographical barriers. PMID- 26802073 TI - Enabling the participation of marginalized populations: case studies from a health service organization in Ontario, Canada. AB - We examined efforts to engage marginalized populations in Ontario Community Health Centers (CHCs), which are primary health care organizations serving 74 high-risk communities. Qualitative case studies of community participation in four Ontario CHCs were carried out through key informant interviews with CHC staff to identify: (i) the approaches, strategies and methods used in participation initiatives aimed specifically at engaging marginalized populations in the planning of and decision making for health services; and (ii) the challenges and enablers for engaging these populations. The marginalized populations involved in the community participation initiatives studied included Low-German Speaking Mennonites in a rural town, newcomer immigrants and refugees in an urban downtown city, immigrant and francophone seniors in an inner city and refugee women in an inner city. Our analysis revealed that enabling the participation of marginalized populations requires CHCs to attend to the barriers experienced by marginalized populations that constrain their participation. Key informants outlined the features of a 'community development approach' that they rely on to address the barriers to marginalized peoples' involvement by strengthening their skills, abilities and leadership in capacity-building activities. The community development approach also shaped the participation methods that were used in the engagement process of CHCs. However, key informants also described the challenges of applying this approach, influenced by the cultural values of some groups, which shaped their willingness and motivation to participate. This study provides further insight into the approach, strategies and methods used in the engagement process to enable the participation of marginalized populations, which may be transferable to other health services settings. PMID- 26802074 TI - Cerebral Activation During Initial Motor Learning Forecasts Subsequent Sleep Facilitated Memory Consolidation in Older Adults. AB - Older adults exhibit deficits in motor memory consolidation; however, little is known about the cerebral correlates of this impairment. We thus employed fMRI to investigate the neural substrates underlying motor sequence memory consolidation, and the modulatory influence of post-learning sleep, in healthy older adults. Participants were trained on a motor sequence and retested following an 8-h interval including wake or diurnal sleep as well as a 22-h interval including a night of sleep. Results demonstrated that a post-learning nap improved offline consolidation across same- and next-day retests. This enhanced consolidation was reflected by increased activity in the putamen and the medial temporal lobe, including the hippocampus, regions that have previously been implicated in sleep dependent neural plasticity in young adults. Moreover, for the first time in older adults, the neural substrates subserving initial motor learning, including the putamen, cerebellum, and parietal cortex, were shown to forecast subsequent consolidation depending on whether a post-learning nap was afforded. Specifically, sufficient activation in a motor-related network appears to be necessary to trigger sleep-facilitated consolidation in older adults. Our findings not only demonstrate that post-learning sleep can enhance motor memory consolidation in older adults, but also provide the system-level neural correlates of this beneficial effect. PMID- 26802075 TI - Evaluation of total knee mechanics using a crouching simulator with a synthetic knee substitute. AB - Mechanical evaluation of total knees is frequently required for aspects such as wear, strength, kinematics, contact areas, and force transmission. In order to carry out such tests, we developed a crouching simulator, based on the Oxford type machine, with novel features including a synthetic knee including ligaments. The instrumentation and data processing methods enabled the determination of contact area locations and interface forces and moments, for a full flexion extension cycle. To demonstrate the use of the simulator, we carried out a comparison of two different total knee designs, cruciate retaining and substituting. The first part of the study describes the simulator design and the methodology for testing the knees without requiring cadaveric knee specimens. The degrees of freedom of the anatomic hip and ankle joints were reproduced. Flexion extension was obtained by changing quadriceps length, while variable hamstring forces were applied using springs. The knee joint was represented by three dimensional printed blocks on to which the total knee components were fixed. Pretensioned elastomeric bands of realistic stiffnesses passed through holes in the block at anatomical locations to represent ligaments. Motion capture of the knees during flexion, together with laser scanning and computer modeling, was used to reconstruct contact areas on the bearing surfaces. A method was also developed for measuring tibial component interface forces and moments as a comparative assessment of fixation. The method involved interposing Tekscan pads at locations on the interface. Overall, the crouching machine and the methodology could be used for many different mechanical measurements of total knee designs, adapted especially for comparative or parametric studies. PMID- 26802076 TI - Clinical effectiveness of orthogeriatric and fracture liaison service models of care for hip fracture patients: population-based longitudinal study. AB - OBJECTIVES: to evaluate orthogeriatric and nurse-led fracture liaison service (FLS) models of post-hip fracture care in terms of impact on mortality (30 days and 1 year) and second hip fracture (2 years). SETTING: Hospital Episode Statistics database linked to Office for National Statistics mortality records for 11 acute hospitals in a region of England. POPULATION: patients aged over 60 years admitted for a primary hip fracture from 2003 to 2013. METHODS: each hospital was analysed separately and acted as its own control in a before-after time-series design in which the appointment of an orthogeriatrician or set up/expansion of an FLS was evaluated. Multivariable Cox regression (mortality) and competing risk survival models (second hip fracture) were used. Fixed effects meta-analysis was used to pool estimates of impact for interventions of the same type. RESULTS: of 33,152 primary hip fracture patients, 1,288 sustained a second hip fracture within 2 years (age and sex standardised proportion of 4.2%). 3,033 primary hip fracture patients died within 30 days and 9,662 died within 1 year (age and sex standardised proportion of 9.5% and 29.8%, respectively). The estimated impact of introducing an orthogeriatrician on 30-day and 1-year mortality was hazard ratio (HR) = 0.73 (95% CI: 0.65-0.82) and HR = 0.81 (CI: 0.75-0.87), respectively. Following an FLS, these associations were as follows: HR = 0.80 (95% CI: 0.71-0.91) and HR = 0.84 (0.77-0.93). There was no significant impact on time to second hip fracture. CONCLUSIONS: the introduction and/or expansion of orthogeriatric and FLS models of post-hip fracture care has a beneficial effect on subsequent mortality. No evidence for a reduction in second hip fracture rate was found. PMID- 26802077 TI - Association of Dementia and Peptic Ulcer Disease: A Nationwide Population-Based Study. AB - OBJECTIVE: We determine the association between dementia and the subsequent peptic ulcer disease (PUD). METHODS: We identified patients with diagnosed dementia in the Taiwan National Health Insurance Research Database. A comparison cohort without dementia was frequency-matched by age, sex, and comorbidities, and the occurrence of PUD was evaluated in both cohorts. RESULTS: The dementia and control cohort consisted of 6014 patients with dementia and 17 830 frequency matched patients without dementia, respectively. The incidence of PUD (hazard ratio, 1.27; 95% confidence interval, 1.18-1.37; P < .001) was higher among patients with dementia. Cox models showed that being female, diabetes mellitus, chronic kidney disease, coronary artery disease, and chronic obstructive pulmonary disease were independent risk factors for PUD in patients with dementia. CONCLUSION: Dementia might increase the risk of developing PUD. PMID- 26802078 TI - Transmembrane segments of complement receptor 3 do not participate in cytotoxic activities but determine receptor structure required for action of Bordetella adenylate cyclase toxin. AB - Adenylate cyclase toxin-hemolysin (CyaA, ACT or AC-Hly) of the whooping cough agent Bordetella pertussis penetrates phagocytes expressing the integrin complement receptor 3 (CR3, CD11b/CD18, alpha(M)beta(2) or Mac-1). CyaA translocates its adenylate cyclase (AC) enzyme domain into cell cytosol and catalyzes unregulated conversion of ATP to cAMP, thereby subverting cellular signaling. In parallel, CyaA forms small cation-selective membrane pores that permeabilize cells for potassium efflux, contributing to cytotoxicity of CyaA and eventually provoking colloid-osmotic cell lysis. To investigate whether the single-pass alpha-helical transmembrane segments of CR3 subunits CD11b and CD18 do directly participate in AC domain translocation and/or pore formation by the toxin, we expressed in CHO cells variants of CR3 that contained artificial transmembrane segments, or lacked the transmembrane segment(s) at all. The results demonstrate that the transmembrane segments of CR3 are not directly involved in the cytotoxic activities of CyaA but serve for maintaining CR3 in a conformation that is required for efficient toxin binding and action. PMID- 26802079 TI - M1 Macrophages Activate Notch Signalling in Epithelial Cells: Relevance in Crohn's Disease. AB - BACKGROUND: The Notch signalling pathway plays an essential role in mucosal regeneration, which constitutes a key goal of Crohn's disease (CD) treatment. Macrophages coordinate tissue repair and several phenotypes have been reported which differ in the expression of surface proteins, cytokines and hypoxia inducible factors (HIFs). We analysed the role of HIFs in the expression of Notch ligands in macrophages and the relevance of this pathway in mucosal regeneration. METHODS: Human monocytes and U937-derived macrophages were polarized towards the M1 and M2 phenotypes and the expression levels of HIF-1alpha, HIF-2alpha, Jagged 1 (Jag1) and delta-like 4 (Dll4) were evaluated. The effects of macrophages on the expression of hairy and enhancer of split-1 (HES1, the main target of Notch signalling) and intestinal alkaline phosphatase (IAP, enterocyte marker) in epithelial cells in co-culture were also analysed. Phenotype macrophage markers and Notch signalling were evaluated in the mucosa of CD patients. RESULTS: M1 macrophages were associated with HIF-1-dependent induction of Jag1 and Dll4, which increased HES1 protein levels and IAP activity in co-cultured epithelial cells. In the mucosa of CD patients a high percentage of M1 macrophages expressed both HIF-1alpha and Jag1 while M2 macrophages mainly expressed HIF-2alpha and we detected a good correlation between the ratio of M1/M2 macrophages and both HES1 and IAP protein levels. CONCLUSION: M1, but not M2, macrophages are associated with HIF-1-dependent induction of Notch ligands and activation of epithelial Notch signalling pathway. In the mucosa of chronic CD patients, the prevalence of M2 macrophages is associated with diminution of Notch signalling and impaired enterocyte differentiation. PMID- 26802080 TI - MicroRNA-124 Promotes Intestinal Inflammation by Targeting Aryl Hydrocarbon Receptor in Crohn's Disease. AB - BACKGROUND AND AIMS: Dysregulation of microRNAs (miRNAs) is associated with a variety of diseases, including Crohn's disease (CD), but the essential biological functions and crucial targets of miRNAs remain largely unknown. The present study investigated the aberrant colonic mucosal miRNAs in active CD patients. METHODS: miRNA levels were assayed in inflamed colon of active CD patients by quantitative real-time polymerase chain reaction. The influence of differential expressed miR 124 on its putative target, the aryl hydrocarbon receptor (AHR), was investigated in CD patients, intestinal epithelial cells (IECs) and 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis mice. The role of miR-124 was further studied in experimental colitis mice by intracolonic administration of miR-124 inhibitors or precursors. RESULTS: We found an inverse correlation between miR 124 and AHR protein levels in colon tissues and IECs of active CD patients. Further results demonstrated that miR-124 suppressed AHR expression by directly targeting the AHR 3'-untranslated region (3'-UTR) in Caco-2 cells and HT-29 cells. MiR-124 mediated the inflammatory response in lipopolysaccharide stimulated cells through retroregulation of AHR in vitro. Downregulation or upregulation of miR-124 in TNBS-induced colitic colon alleviated or aggravated experimental colitis, respectively. CONCLUSIONS: These findings suggest that miR 124 induces intestinal inflammation by inhibiting AHR to modulate pro inflammatory cytokine production and thereby promotes the pathogenesis of CD. PMID- 26802081 TI - Use of Anti-TNFalpha Agents and Time to First-time Surgery in Paediatric Patients with Ulcerative Colitis and Crohn's Disease. AB - BACKGROUND AND AIMS: It is debated whether the need for surgery has changed following introduction of anti-TNFalpha agents in the treatment of paediatric ulcerative colitis [UC] and Crohn's disease [CD]. We aimed to describe the implementation of anti-TNFalpha agents in paediatric patients, and the need of first-time surgery before and after introduction of anti-TNFalpha agents. METHODS: In the Danish National Patient Registry, we identified incident paediatric patients diagnosed from 1998. We calculated the proportion of patients receiving anti-TNFalpha agents within 5 years from diagnosis, and the cumulative 5 year proportion of surgery, according to calendar periods of diagnosis. RESULTS: At the end of our study period [2007 and 2008], 29-41% of CD children were treated with anti-TNFalpha agents within 5 years, and for UC children 17 19%. In 1278 CD patients, the 5 year cumulative proportions of surgery were 14.6 15.6% for children diagnosed in 1998-2008 and 9.7% (95% confidence interval [CI]: 6.7-13.7) for those diagnosed in 2009-2013. In 1468 UC patients, the cumulative proportion of surgery suggested a decline in patients diagnosed after mid 2005, and the hazard ratio of surgery was 0.64 [95% CI: 0.47-0.86] after the introduction of anti-TNFalpha agents compared with before. For UC patients diagnosed in 2009-2013, the 5 year cumulative proportion of surgery was 7.6% [95% CI: 5.2-11.2]. CONCLUSIONS: This nationwide study showed an extensive use of anti TNFalpha agents at the end of our study period. For UC children, our data suggest a decline in the proportion of surgery in the period of increasing use of anti TNFalpha agents. PMID- 26802082 TI - Dysregulated Lysine Acetyltransferase 2B Promotes Inflammatory Bowel Disease Pathogenesis Through Transcriptional Repression of Interleukin-10. AB - BACKGROUND AND AIMS: Accumulating evidence supports epigenetic modifications in mediating intestinal immunity in inflammatory bowel disease [IBD] pathogenesis. This study aimed to identify key dysregulated epigenetic modulators and the molecular downstream pathways in IBD. METHODS: Expression of 116 well-defined epigenetic modulators was profiled and validated in 96 intestinal tissues from patients with Crohn's disease [CD], ulcerative colitis [UC], and healthy controls using quantitative reverse transcriptase polymerase chain reaction [QRT-PCR], western blot, and immunohistochemistry. Dysregulation of histone modifications and IBD-related cytokines were examined by chromatin immunoprecipitation, luciferase activity, and gene expression analyses in normal colonic epithelial cell line, NCM460, upon small-molecule inhibition or RNA interference, followed by validation in primary colonic tissues. RESULTS: Targeted expression profiling uncovered seven differentially expressed epigenetic modulators, of which the down regulation of lysine acetyltransferase 2B [KAT2B] mRNA and protein was the most significant and was consequently validated in inflamed CD and UC compared with healthy colonic tissues. KAT2B protein localised abundantly in nuclei of normal colonic epithelium but diminished in paired inflamed CD and UC tissues. Pharmacological inhibition of KAT2B by anacardic acid in NCM460 cells reduced the levels of histone H4 lysine 5 acetylation [H4K5ac] and interleukin-10 [IL-10] in a dose-dependent manner. Knockdown of KAT2B reduced the IL-10 promoter occupancy of KAT2B and H4K5ac, resulting in transcriptional silencing. IL-10 level was also diminished in inflamed IBD tissues. CONCLUSIONS: Our findings demonstrated a novel epigenetic mechanism of IL-10 dysregulation in IBD. Down-regulation of KAT2B may disrupt the innate and adaptive inflammatory responses due to the suppression of this crucial anti-inflammatory cytokine. PMID- 26802083 TI - Consecutive Measurements by Faecal Immunochemical Test in Quiescent Ulcerative Colitis Patients Can Detect Clinical Relapse. AB - BACKGROUND: We have reported that results of the quantitative faecal immunochemical test (FIT; haemoglobin concentrations in faeces measured using an antibody for human haemoglobin) effectively reflect the mucosal status of ulcerative colitis (UC). The aim of this study was to evaluate the predictability of flare-up in quiescent UC patients by consecutive FIT evaluation. METHODS: Patients with UC who fulfilled the following criteria by index colonoscopy were enrolled: clinical remission; mucosal healing (Mayo endoscopic subscore 0); and negative FIT (less than 100ng/mL). These patients were followed up prospectively every 1-3 months by monitoring patient symptoms and FIT results between index and subsequent colonoscopies. RESULTS: The intervals between 2 colonoscopies (median 2.51 years) of 83 patients (49 males, median age at onset 34 years, median disease duration 9.74 years) were analysed. None of the 43 (52%) patients who maintained negative FIT throughout the observation period exhibited clinical relapse. On the other hand, 25/40 (63%) patients who showed positive conversion of FIT during the period experienced relapse. The cutoff FIT value of 450ng/mL could predict relapse with 73% positive predictive value and 96% negative predictive value. Moreover, positive conversion of FIT preceded occurrence of symptoms by 1 month or more in nearly one-third of patients with relapse. CONCLUSIONS: Consecutive measurements of FIT in quiescent UC patients who achieved mucosal healing with negative FIT would help identify patients with clinical relapse whose symptoms had not yet presented. Further investigations are required for more precise prediction of relapse with this modality. PMID- 26802084 TI - Anti-TNF Monotherapy for Crohn's Disease: a 13-year Multicentre Experience. AB - BACKGROUND: Anti-tumour necrosis factor [TNF] therapy in combination with thiopurine is the most effective strategy for Crohn's disease, but raises safety concerns. METHODS: In a retrospective multicentre study, we investigated long term outcome of patients starting anti-TNF monotherapy for Crohn's disease and investigated whether introducing an immunomodulator in patients losing response to anti-TNF monotherapy is effective for resetting immunogenicity. RESULTS: A total of 350 adult patients with Crohn's disease received either infliximab [n = 178, 51%] or adalimumab [n = 172, 49%] monotherapy. Mean duration of follow-up was 42 months. An immunomodulator was initiated in 53 patients [15%]. At last follow-up, 73.1% [n = 38] were in clinical remission [one patient with missing data]. Multivariate analysis identified anti-TNF type [higher need for starting immunomodulator for infliximab than for adalimumab; p = 0.0058] and first- vs second-/third-/fourth-line anti-TNF therapy [p = 0.014] as predictors of immunomodulator initiation. Among the 18 patients with available data, introduction of an immunomodulator was able to restore infliximab trough level within the therapeutic range and to induce clinical remission in 10 patients [55%]. Cumulative probability of remaining on anti-TNF therapy was 57.9% at 5 years among the 297 patients not starting an immunomodulator during follow-up. CONCLUSION: An immunomodulator was initiated in 15% of patients with Crohn's disease starting anti-TNF monotherapy. Independent predictors of immunomodulator initiation were infliximab use and second-/third-/fourth-line anti-TNF therapy. Resetting immunogenicity with an immunomodulator was effective in half of patients in a sub-study. Persistence of anti-TNF treatment at 5 years was observed in half of the 297 patients not starting an immumodulator in a real-life setting. PMID- 26802086 TI - Meta-omics in Inflammatory Bowel Disease Research: Applications, Challenges, and Guidelines. AB - Meta-omics [metagenomics, metatranscriptomics, and metaproteomics] are rapidly expanding our knowledge of the gut microbiota in health and disease. These technologies are increasingly used in inflammatory bowel disease [IBD] research. Yet, meta-omics data analysis, interpretation, and among-study comparison remain challenging. In this review we discuss the role these techniques are playing in IBD research, highlighting their strengths and limitations. We give guidelines on proper sample collection and preparation methods, and on performing the analyses and interpreting the results, reporting available user-friendly tools and pipelines. PMID- 26802085 TI - Tuberculosis in Anti-Tumour Necrosis Factor-treated Inflammatory Bowel Disease Patients After the Implementation of Preventive Measures: Compliance With Recommendations and Safety of Retreatment. AB - BACKGROUND AND AIMS: Despite having adopted preventive measures, tuberculosis (TB) may still occur in patients with inflammatory bowel disease (IBD) treated with anti-tumour necrosis factor (anti-TNF). Data on the causes and characteristics of TB cases in this scenario are lacking. Our aim was to describe the characteristics of TB in anti-TNF-treated IBD patients after the publication of the Spanish TB prevention guidelines in IBD patients and to evaluate the safety of restarting anti-TNF after a TB diagnosis. METHODS: In this multicentre, retrospective, descriptive study, TB cases from Spanish hospitals were collected. Continuous variables were reported as mean and standard deviation or median and interquartile range. Categorical variables were described as absolute and relative frequencies and their confidence intervals when necessary. RESULTS: We collected 50 TB cases in anti-TNF-treated IBD patients, 60% male, median age 37.3 years (interquartile range [IQR] 30.4-47). Median latency between anti-TNF initiation and first TB symptoms was 155.5 days (IQR 88-301); 34% of TB cases were disseminated and 26% extrapulmonary. In 30 patients (60%), TB cases developed despite compliance with recommended preventive measures; *not performing 2-step TST (tuberculin skin test) was the main failure in compliance with recommendations. In 17 patients (34%) anti-TNF was restarted after a median of 13 months (IQR 7.1-17.3) and there were no cases of TB reactivation. CONCLUSIONS: Tuberculosis could still occur in anti-TNF-treated IBD patients despite compliance with recommended preventive measures. A significant number of cases developed when these recommendations were not followed. Restarting anti-TNF treatment in these patients seems to be safe. PMID- 26802088 TI - Targets for Health Interventions for Inflammatory Bowel Disease-fatigue. AB - BACKGROUND AND AIMS: Fatigue is a complex, multifactorial, and multidimensional phenomenon. Recognition of modifiable correlates of fatigue can provide a further understanding of this phenomenon in patients with inflammatory bowel disease [IBD] and aid in the development of interventions tailored towards fatigue with potential for efficacy. Our aims were to systematically search and synthesise available evidence on potentially modifiable factors contributing to IBD-fatigue and what advances in the management of fatigue in individuals with IBD have been made. METHODS: The process of selection of citations was based on an earlier review by Czuber-Dochan et al. [2013] and was undertaken in two phases: i] searching for new studies published since August 2012, using seven electronic databases; ii] re-selection of papers included in previous review according to the aims of the current review. RESULTS: A total of 43 studies met the inclusion criteria. IBD-fatigue was consistently associated with disease activity, depression, anxiety, and sleep difficulties. However, most studies were cross sectional; thus the direction of causation remains unknown. The relationship between biochemical factors, such as anaemia and inflammation, and fatigue was inconsistent. Solution-focused therapy, thiamine, and exercise showed promising effects on IBD-fatigue. Interventions continue to be sparse, with methodological limitations and only short-term effects reported. CONCLUSIONS: The review identified a number of psychosocial and physical factors which could potentially be modified through targeted health interventions and improve fatigue in IBD. Research utilising prospective observational studies and randomized control trial [RCT] design is required to develop and test interventions to reduce fatigue, most likely within a biopsychosocial model of care. PMID- 26802087 TI - Effects of AVX-470, an Oral, Locally Acting Anti-Tumour Necrosis Factor Antibody, on Tissue Biomarkers in Patients with Active Ulcerative Colitis. AB - BACKGROUND AND AIMS: AVX-470 is an orally administered, bovine-derived, anti tumour necrosis factor (TNF) antibody with local activity in the gastrointestinal tract. In the first-in-human clinical trial of AVX-470 in active ulcerative colitis, we evaluated inflammatory biomarkers in colon tissue as measures of disease activity and early response to treatment. METHODS: Thirty-six patients received active drug (AVX-470 at 0.2, 1.6 or 3.5g/day) or placebo over 4 weeks. Colon biopsy samples were collected from 5 regions of colon at baseline and week 4. Tissue inflammatory biomarkers were evaluated by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), epithelial cell apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and bovine immunoglobulin by immunohistochemistry and mass spectrometry. Endoscopic activity (Ulcerative Colitis Endoscopic Index of Severity [UCEIS]) at colonoscopy was assessed in each colonic region by a central reader. RESULTS: Bovine immunoglobulin was observed in mucosal tissue before and after dosing in lamina propria and submucosal layers of biopsy tissue. Baseline levels of TNF, myeloperoxidase (MPO), CD68 and interleukin (IL)-1beta and, to a lesser extent, IL-6 mRNA were 2- to 3-fold higher in distal vs proximal colon tissue, corresponding to the 2- to 3-fold differences in baseline severities of endoscopic scores. Reductions of >10-fold in TNF and, to lesser extents, in MPO and epithelial cell apoptosis were observed in proximal and distal colon biopsies after 4 weeks of AVX-470 3.5g/day treatment. Reductions in TNF scores were correlated with changes in MPO and CD3 immunohistochemistry scores. CONCLUSIONS: These results are consistent with anti-TNF activity of orally administered AVX 470 in colon mucosal tissue in ulcerative colitis patients and demonstrate the utility of tissue biomarkers in assessing disease and treatment response in early clinical studies. CLINICAL TRIAL REGISTRATION NUMBER: This trial was registered with Clinicaltrials.gov as study NCT01759056 and with EudraCT as study 2012 004859-27. PMID- 26802089 TI - Transient ischemic attack service provision: A review of available service models. AB - TIAs are predictors of high risk of subsequent stroke and require urgent intervention to maximize secondary prevention and minimize adverse health outcomes. TIA patients are often admitted to the hospital to facilitate rapid investigation and comprehensive management. However, over the last 2 decades, alternative service models have emerged in an effort to optimize health resource utilization without compromising patient outcomes. This article reviews recommended interventions and then discusses the inpatient and 6 alternative TIA service models to help modern stroke services determine the model best suited to their local health service environment. PMID- 26802091 TI - Change in PDE10 across early Huntington disease assessed by [18F]MNI-659 and PET imaging. AB - OBJECTIVE: To evaluate whether striatal [(18)F]MNI-659 PET imaging of phosphodiesterase 10A (PDE10) serves as a sensitive and reliable biomarker of striatal neurodegeneration in a longitudinal cohort of participants with early Huntington disease (HD). METHODS: A cohort of participants with HD, including both participants premanifest or manifest with motor signs, underwent clinical assessments, genetic determination, and 2 [(18)F]MNI-659 PET imaging sessions approximately 1 year apart. Eleven healthy control (HC) participants underwent clinical assessments and [(18)F]MNI-659 PET imaging once. Striatal binding potentials (BPnd) were estimated for brain regions of interest, specifically within the basal ganglia, and compared between baseline and follow-up imaging. Clinical measures of HD severity were assessed at each visit. RESULTS: Eight participants with HD (6 manifest; 2 premanifest) participated. Of those with manifest HD, all had relatively early stage disease (stage 1, n = 2; stage 2, n = 4) and a Unified Huntington's Disease Rating Scale total motor score <45. As expected, the HD cohort as a whole had a reduction in the basal ganglia BPnd to approximately 50% of that seen in HC. On follow-up scans, [(18)F]MNI-659 uptake declined in the putamen and caudate nucleus in all 8 participants. The mean annualized rates of decline in signal in the caudate, putamen, and globus pallidus and the putamen were 16.6%, 6.9%, and 5.8%, respectively. In HC, the annualized reduction in signal in striatal regions was less than 1%. CONCLUSION: Longitudinal data in this small cohort of participants with early HD support [(18)F]MNI-659 PET imaging of PDE10 as a useful biomarker to track HD disease progression. PMID- 26802092 TI - Comment: Plateaus and reversals in ALS disease course or limitations of trial design? PMID- 26802090 TI - Effect of endovascular reperfusion in relation to site of arterial occlusion. AB - OBJECTIVE: To assess whether the association between reperfusion and improved clinical outcomes after stroke differs depending on the site of the arterial occlusive lesion (AOL). METHODS: We pooled data from Solitaire With the Intention for Thrombectomy (SWIFT), Solitaire FR Thrombectomy for Acute Revascularisation (STAR), Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), and Interventional Management of Stroke Trial (IMS III) to compare the strength of the associations between reperfusion and clinical outcomes in patients with internal carotid artery (ICA), proximal middle cerebral artery (MCA) (M1), and distal MCA (M2/3/4) occlusions. RESULTS: Among 710 included patients, the site of the AOL was the ICA in 161, the proximal MCA in 389, and the distal MCA in 160 patients (M2 = 131, M3 = 23, and M4 = 6). Reperfusion was associated with an increase in the rate of good functional outcome (modified Rankin Scale [mRS] score 0-2) in patients with ICA (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.7-7.2) and proximal MCA occlusions (OR 6.2, 95% CI 3.8-10.2), but not in patients with distal MCA occlusions (OR 1.4, 95% CI 0.8-2.6). Among patients with M2 occlusions, a subset of the distal MCA cohort, reperfusion was associated with excellent functional outcome (mRS 0-1; OR 2.2, 95% CI 1.0-4.7). CONCLUSIONS: The association between endovascular reperfusion and better clinical outcomes is more profound in patients with ICA and proximal MCA occlusions compared to patients with distal MCA occlusions. Because there are limited data from randomized controlled trials on the effect of endovascular therapy in patients with distal MCA occlusions, these results underscore the need for inclusion of this subgroup in future endovascular therapy trials. PMID- 26802093 TI - Cognition and neuropsychiatry in behavioral variant frontotemporal dementia by disease stage. AB - OBJECTIVE: To characterize the cognitive and neuropsychiatric symptoms of patients with behavioral variant frontotemporal dementia (bvFTD) over the natural course of the disease. METHODS: We examined the initial and subsequent neuropsychological test performance and neuropsychiatric symptoms in a large cohort of patients with bvFTD (n = 204) across progressive stages of disease as measured by the Clinical Dementia Rating (CDR). We also compared cognitive and neuropsychiatric impairments of patients with bvFTD to those of an age-matched cohort with Alzheimer disease (AD) dementia (n = 674). RESULTS: At the earliest stage (CDR = 0.5), patients with bvFTD had profound neuropsychiatric disturbances, insensitivity to errors, slower response times, and poor naming, with intact attention span, memory, and facial affect naming. Tests continuing to show progressive, statistically significant stepwise declines after the CDR = 1 stage included free recall, visuoconstruction, set-shifting, error insensitivity, semantic fluency, design fluency, emotion naming, calculations, confrontation naming, syntax comprehension, and verbal agility. At CDR = 0.5, patients with bvFTD significantly outperformed patients with AD in episodic memory and were faster in set-shifting, while scoring quantitatively worse in lexical fluency, emotion naming, and error sensitivity. The overall rate of disease progression in bvFTD was more rapid than in AD. CONCLUSION: There are distinct patterns of cognitive deficits differentiating the earlier and later disease stages in bvFTD, with the pattern of cognitive decline revealing in greater detail the natural history of the disease. These cognitive symptoms are readily apparent clinical markers of dysfunction in the principal brain networks known to undergo molecular and anatomical changes in bvFTD, thus are important indicators of the evolving pathology in individual patients. PMID- 26802096 TI - Community-acquired bacterial meningitis in adults with cancer or a history of cancer. AB - OBJECTIVES: To study the incidence, clinical presentation, causative bacteria, and outcome of community-acquired bacterial meningitis in adults with cancer. METHODS: We evaluated incidence and characteristics of patients with cancer included in a nationwide prospective cohort study of adults with community acquired meningitis performed in the Netherlands from March 1, 2006, to September 31, 2014. All patients underwent a neurologic examination at hospital discharge, and outcome was graded using the Glasgow Outcome Scale. RESULTS: Active cancer was identified in 68 of 1,351 episodes (5%) and a history of cancer in 87 (6%). The annual incidence of community-acquired bacterial meningitis was 2.71-fold (95% confidence interval [CI] 1.68-4.36, p < 0.001) increased for patients with cancer compared to patients without cancer in 2010, and 3.52-fold (95% CI 2.16 5.73, p < 0.001) in 2013. The clinical presentation of bacterial meningitis in patients with cancer compared to patients without cancer was similar. Patients with active cancer presented with lower leukocyte count in blood (12.1 * 10(9) cells/L vs 17.3 * 10(9) cells/L, p < 0.001) and CSF (670 cells/mm(3) vs 2,567 cells/mm(3), p < 0.001) and were more likely to be infected with Listeria monocytogenes (21% vs 5%, p < 0.001) than patients without cancer. Active cancer was identified as an independent risk factor for unfavorable outcome in bacterial meningitis (odds ratio 1.85, 95% CI 1.09-3.13). CONCLUSIONS: One of 8 patients with community-bacterial meningitis was identified to have a history of cancer and cancer was considered active in half of these patients. Patients with active cancer present with lower CSF leukocyte counts, are more likely to be infected with L monocytogenes, and are at high risk of unfavorable outcome. PMID- 26802097 TI - Pursuing "model care" of transient ischemic attacks. PMID- 26802094 TI - Cognitive-behavioral screening reveals prevalent impairment in a large multicenter ALS cohort. AB - OBJECTIVES: To characterize the prevalence of cognitive and behavioral symptoms using a cognitive/behavioral screening battery in a large prospective multicenter study of amyotrophic lateral sclerosis (ALS). METHODS: Two hundred seventy-four patients with ALS completed 2 validated cognitive screening tests and 2 validated behavioral interviews with accompanying caregivers. We examined the associations between cognitive and behavioral performance, demographic and clinical data, and C9orf72 mutation data. RESULTS: Based on the ALS Cognitive Behavioral Screen cognitive score, 6.5% of the sample scored below the cutoff score for frontotemporal lobar dementia, 54.2% scored in a range consistent with ALS with mild cognitive impairment, and 39.2% scored in the normal range. The ALS Cognitive Behavioral Screen behavioral subscale identified 16.5% of the sample scoring below the dementia cutoff score, with an additional 14.1% scoring in the ALS behavioral impairment range, and 69.4% scoring in the normal range. CONCLUSIONS: This investigation revealed high levels of cognitive and behavioral impairment in patients with ALS within 18 months of symptom onset, comparable to prior investigations. This investigation illustrates the successful use and scientific value of adding a cognitive-behavioral screening tool in studies of motor neuron diseases, to provide neurologists with an efficient method to measure these common deficits and to understand how they relate to key clinical variables, when extensive neuropsychological examinations are unavailable. These tools, developed specifically for patients with motor impairment, may be particularly useful in patient populations with multiple sclerosis and Parkinson disease, who are known to have comorbid cognitive decline. PMID- 26802095 TI - Multiplex families with epilepsy: Success of clinical and molecular genetic characterization. AB - OBJECTIVE: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis. METHODS: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis. Pedigrees were analyzed and molecular genetic studies were performed as appropriate. RESULTS: A total of 211 families were ascertained over an 11-year period in Israel. A total of 169 were classified into broad familial epilepsy syndrome groups: 61 generalized, 22 focal, 24 febrile seizure syndromes, 33 special syndromes, and 29 mixed. A total of 42 families remained unclassified. Pathogenic variants were identified in 49/211 families (23%). The majority were found in established epilepsy genes (e.g., SCN1A, KCNQ2, CSTB), but in 11 families, this cohort contributed to the initial discovery (e.g., KCNT1, PCDH19, TBC1D24). We expand the phenotypic spectrum of established epilepsy genes by reporting a familial LAMC3 homozygous variant, where the predominant phenotype was epilepsy with myoclonic-atonic seizures, and a pathogenic SCN1A variant in a family where in 5 siblings the phenotype was broadly consistent with Dravet syndrome, a disorder that usually occurs sporadically. CONCLUSION: A total of 80% of families were successfully classified, with pathogenic variants identified in 23%. The successful characterization of familial electroclinical and inheritance patterns has highlighted the value of studying multiplex families and their contribution towards uncovering the genetic basis of the epilepsies. PMID- 26802098 TI - Electronic epidemiology and the risk of cardiovascular disease in inflammatory rheumatic diseases. PMID- 26802099 TI - Hand-held cardiac ultrasound screening performed by family doctors with remote expert support interpretation. AB - OBJECTIVE: To assess the usefulness of hand-held cardiac ultrasound (HCU) performed by family doctors (FDs) in primary care, with web-based remote expert support interpretation, in a cohort of patient with symptoms or physical examination signs suggestive of cardiovascular disease. METHODS: This prospective observational study included 1312 consecutive patients, in three remote primary care areas, with symptoms or physical examination signs suggestive of cardiovascular disease. In 859 patients (group A), FDs had indicated conventional echocardiography (CE), and in 453 (Group B) the study was performed to complement the physical examination. HCU was carried out by 14 FDs after a short training period. The scans and preliminary FD reports were uploaded on a web-based program for remote expert support interpretation in <24 h. RESULTS: Experts considered HCU to be inconclusive in 116 (8.8%) patients. FD and expert agreement on diagnosis was moderate (K=0.40-0.70) except in mitral stenosis (K=0.29) and in left atrial dilation (K=0.38). Diagnostic agreement between expert interpretation and CE was good (K=0.66-0.85) except in mitral stenosis (K=0.43). After remote expert interpretation, conventional echocardiograms were finally requested by FDs in only 276 (32.1%) patients, and discharges increased by 10.2%. Furthermore, significant heart diseases were diagnosed in 32 (7%) patients of group B. CONCLUSIONS: HCU performed at the point of care by FDs with remote expert support interpretation using a web-based system is feasible, rapid and useful for detecting significant echocardiographic abnormalities and reducing the number of unnecessary echocardiographic studies. PMID- 26802100 TI - Cardiac Trauma. AB - Cardiac trauma is a leading cause of death in the United States and occurs mostly due to motor vehicle accidents. Blunt cardiac trauma and penetrating chest injuries are most common, and both can lead to aortic injuries. Timely diagnosis and early management are the key to improve mortality. Cardiac computed tomography and cardiac ultrasound are the 2 most important diagnostic modalities. Mortality related to cardiac trauma remains high despite improvement in diagnosis and management. PMID- 26802101 TI - Editorial: Candida glabrata, the other yeast pathogen. PMID- 26802102 TI - Response to "Discourse over a contested technology on Twitter: A case study of hydraulic fracturing"-Word choice as political speech. AB - Hopke and Simis ( Public Understanding of Science, online 4 October 2015) find that #fracking, the most popular of five shale-related hashtags analyzed from a 2013 period, is associated with pro-shale attitudes only 13% of the time and note that the dominant voice of the activist community, coupled with a lack of engagement from industry, is unexpected. This comment offers additional perspective on the sentiment- and actor-skewed result by noting that the term "fracking" is highly political, specifically because the spelling "frack" versus "frac" is associated with activism. Furthermore, in public speech, the industry tends to deemphasize the hydraulic fracturing process in favor of the product, consistent with the findings that #natgas is a relatively pro-industry hashtag. PMID- 26802103 TI - Scientific evidence and mass media: Investigating the journalistic intention to represent scientific uncertainty. AB - Science journalists are responsible for the mass media's representation of life sciences (e.g. biotechnology, genetics, and nanotechnology) and for the depiction of research findings in these areas as more scientifically (un)certain. Although researchers have determined that the representational styles of scientific evidence vary among science journalists, the reasons for these differences have not yet been fully investigated. Against this background, for the first time, the present study applies a reasoned action approach and investigates the predictors of the journalistic intention to represent scientific uncertainty, using computer assisted telephone interviews with a representative sample of German science journalists (n = 202). The results indicate that beliefs about the coverage of other media, perceptions regarding scientific uncertainty of the main field of coverage, perceived expectations of the audience, past behavior, and gender were the predictors that most strongly affected the journalists' intention to represent life sciences as more scientifically uncertain. PMID- 26802104 TI - Rescue of Pressure Overload-Induced Heart Failure by Estrogen Therapy. AB - BACKGROUND: Estrogen pretreatment has been shown to attenuate the development of heart hypertrophy, but it is not known whether estrogen could also rescue heart failure (HF). Furthermore, the heart has all the machinery to locally biosynthesize estrogen via aromatase, but the role of local cardiac estrogen synthesis in HF has not yet been studied. Here we hypothesized that cardiac estrogen is reduced in HF and examined whether exogenous estrogen therapy can rescue HF. METHODS AND RESULTS: HF was induced by transaortic constriction in mice, and once mice reached an ejection fraction (EF) of ~35%, they were treated with estrogen for 10 days. Cardiac structure and function, angiogenesis, and fibrosis were assessed, and estrogen was measured in plasma and in heart. Cardiac estrogen concentrations (6.18+/-1.12 pg/160 mg heart in HF versus 17.79+/-1.28 pg/mL in control) and aromatase transcripts (0.19+/-0.04, normalized to control, P<0.05) were significantly reduced in HF. Estrogen therapy increased cardiac estrogen 3-fold and restored aromatase transcripts. Estrogen also rescued HF by restoring ejection fraction to 53.1+/-1.3% (P<0.001) and improving cardiac hemodynamics both in male and female mice. Estrogen therapy stimulated angiogenesis as capillary density increased from 0.66+/-0.07 in HF to 2.83+/-0.14 (P<0.001, normalized to control) and reversed the fibrotic scarring observed in HF (45.5+/-2.8% in HF versus 5.3+/-1.0%, P<0.001). Stimulation of angiogenesis by estrogen seems to be one of the key mechanisms, since in the presence of an angiogenesis inhibitor estrogen failed to rescue HF (ejection fraction=29.3+/ 2.1%, P<0.001 versus E2). CONCLUSIONS: Estrogen rescues pre-existing HF by restoring cardiac estrogen and aromatase, stimulating angiogenesis, and suppressing fibrosis. PMID- 26802107 TI - A diagnosis not to get stuck on. PMID- 26802106 TI - Primary healthcare provider knowledge, beliefs and clinic-based practices regarding alternative tobacco products and marijuana: a qualitative study. AB - Use prevalence of alternative tobacco products and marijuana has increased dramatically. Unfortunately, clinical guidelines have focused on traditional cigarettes with limited attention regarding these emerging public health issues. Thus, it is critical to understand how healthcare professionals view this issue and are responding to it. This qualitative study explored knowledge, beliefs and clinic-based practices regarding traditional and alternative tobacco products (cigar-like products, smokeless tobacco, hookah, e-cigarettes) and marijuana among rural and urban Georgia primary healthcare providers. The sample comprised 20 healthcare providers in primary care settings located in the Atlanta Metropolitan area and rural southern Georgia who participated in semi-structured interviews. Results indicated a lack of knowledge about these products, with some believing that some products were less harmful than traditional cigarettes or that they may be effective in promoting cessation or harm reduction. Few reported explicitly assessing use of these various products in clinic. In addition, healthcare providers reported a need for empirical evidence to inform their clinical practice. Healthcare providers must systematically assess use of the range of tobacco products and marijuana. Evidence-based recommendations or information sources are needed to inform clinical practice and help providers navigate conversations with patients using or inquiring about these products. PMID- 26802105 TI - Serum Magnesium and the Risk of Death From Coronary Heart Disease and Sudden Cardiac Death. AB - BACKGROUND: Low serum magnesium has been implicated in cardiovascular mortality, but results are conflicting and the pathway is unclear. We studied the association of serum magnesium with coronary heart disease (CHD) mortality and sudden cardiac death (SCD) within the prospective population-based Rotterdam Study, with adjudicated end points and long-term follow-up. METHODS AND RESULTS: Nine-thousand eight-hundred and twenty participants (mean age 65.1 years, 56.8% female) were included with a median follow-up of 8.7 years. We used multivariable Cox proportional hazard models and found that a 0.1 mmol/L increase in serum magnesium level was associated with a lower risk for CHD mortality (hazard ratio: 0.82, 95% CI 0.70-0.96). Furthermore, we divided serum magnesium in quartiles, with the second and third quartile combined as reference group (0.81-0.88 mmol/L). Low serum magnesium (<=0.80 mmol/L) was associated with an increased risk of CHD mortality (N=431, hazard ratio: 1.36, 95% CI 1.09-1.69) and SCD (N=217, hazard ratio: 1.54, 95% CI 1.12-2.11). Low serum magnesium was associated with accelerated subclinical atherosclerosis (expressed as increased carotid intima-media thickness: +0.013 mm, 95% CI 0.005-0.020) and increased QT-interval, mainly through an effect on heart rate (RR-interval: -7.1 ms, 95% CI -13.5 to 0.8). Additional adjustments for carotid intima-media thickness and heart rate did not change the associations with CHD mortality and SCD. CONCLUSIONS: Low serum magnesium is associated with an increased risk of CHD mortality and SCD. Although low magnesium was associated with both carotid intima-media thickness and heart rate, this did not explain the relationship between serum magnesium and CHD mortality or SCD. Future studies should focus on why magnesium associates with CHD mortality and SCD and whether intervention reduces these risks. PMID- 26802108 TI - Public and patient involvement in paediatric research. PMID- 26802110 TI - Intrauterine growth restriction predicts lower lung function at school age in children born very preterm. AB - OBJECTIVE: Children born preterm have lower lung function compared with term-born children. Intrauterine growth restriction (IUGR) may predispose individuals to chronic obstructive pulmonary disease. The purpose of this observational study was to investigate the role of IUGR as predictor of lung function at school age in children born very preterm. We further studied the difference in lung function between term-born and preterm-born children with distinct morbidities. DESIGN: Preterm-born children and age-matched and sex-matched term-born comparison groups (88 of each) were studied at the mean age of 11 years. Spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) were recorded. All preterm-born subjects with IUGR (n=23), defined as birth weight less than -2 SD, were compared with preterm-born subjects without IUGR (n=65). RESULTS: In the preterm-born children exposed to IUGR, the forced expiratory volume in 1 s (FEV1) was 5.7 (95% CI -10.2 to -1.3) and DLCO 9.2 percentage points lower (95% CI -15.7 to -2.7) than in the preterm-born children with appropriate in utero growth (expressed as percentage of predicted values). The effect of IUGR in decreasing FEV1 and DLCO remained significant after adjustment for bronchopulmonary dysplasia (BPD). Further study indicated that after adjustment with IUGR and BPD, prematurity explained reduction in FEV1 but not in DLCO. CONCLUSIONS: In children born very preterm, IUGR is an independent risk factor for a lower lung function in school age. We propose that IUGR and BPD are the major early factors predisposing the children born very preterm to lower lung function. PMID- 26802111 TI - Prediction of infant extubation outcomes using the tension-time index. AB - OBJECTIVE: The tension-time index of the diaphragm (TTdi) is a composite assessment of the load on and the capacity of the diaphragm. TTmus is a non invasive tension-time index of the respiratory muscles. Our aim was to determine whether TTdi or TTmus predicted extubation outcome and performed better than respiratory muscle strength (Pimax, Pdimax), respiratory drive (P0.1) and work of breathing (transdiaphragmatic pressure-time product (PTPdi)) or routinely available clinical data. DESIGN: Prospective study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: Sixty infants, median gestation age 35 (range 23 42) weeks and postnatal age of 55 (range 1-115) days. INTERVENTIONS: Airway occlusions were performed to measure Pimax, Pdimax and P0.1. TTdi and PTPdi were derived from measurements of transdiaphragmatic pressure. TTmus was derived from airway pressure measurements. Measurements were made within 6 h of extubation. MAIN OUTCOME MEASURES: Extubation failure defined as reintubation within 48 h of extubation. RESULTS: Twelve infants failed extubation. The infants who failed extubation were significantly more immature (medians 25 vs 37 weeks) and of greater postnatal age (23 vs 5 days) and had higher TTdi (0.15 vs 0.04) and TTmus (0.17 vs 0.08). TTdi and TTmus were only significantly better predictors than the peak inflation pressure immediately prior to extubation and did not perform significantly better than gestational age or birth weight. CONCLUSIONS: Assessment of TTdi and TTmus cannot be recommended for use in routine clinical practice. PMID- 26802109 TI - The Nrf2 Activator Vinylsulfone Reduces High Glucose-Induced Neural Tube Defects by Suppressing Cellular Stress and Apoptosis. AB - The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is one of the primary pathways responsible for the cellular defense system against oxidative stress. Oxidative stress-induced apoptosis is a causal event in diabetic embryopathy. Thus, the Nrf2 pathway may play an important role in the induction of diabetic embryopathy. In the present study, we investigated the potentially protective effect of the Nrf2 activator, vinylsulfone, on high glucose-induced cellular stress, apoptosis, and neural tube defects (NTDs). Embryonic day 8.5 (E8.5) whole mouse embryos were cultured in normal (5 mmol/L) or high (16.7 mmol/L) glucose conditions, with or without vinylsulfone. At a concentration of 10 MUmol/L, vinylsulfone had an inhibitory effect on high glucose-induced NTD formation, but it was not significant. At a concentration of 20 MUmol/L, vinylsulfone significantly reduced high glucose-induced NTDs. In addition, 20 MUmol/L vinylsulfone abrogated the high glucose-induced oxidative stress markers lipid hydroperoxide (LPO), 4-hydroxynonenal (4-HNE), and nitrotyrosine-modified proteins. The high glucose-induced endoplasmic reticulum (ER) stress biomarkers were also suppressed by 20 MUmol/L vinylsulfone through the inhibition of phosphorylated protein kinase RNA-like ER kinase (PERK), inositol requiring protein 1alpha (IRE1a), eukaryotic initiation factor 2alpha (eIF2a), upregulated C/EBP-homologous protein (CHOP), binding immunoglobulin protein (BiP), and x-box binding protein 1 (XBP1) messenger RNA splicing. Furthermore, 20 MUmol/L vinylsulfone abolished caspase 3 and caspase 8 cleavage, markers of apoptosis, in embryos cultured under high glucose conditions. The Nrf2 activator, vinylsulfone, is protective against high glucose-induced cellular stress, caspase activation, and subsequent NTD formation. Our data suggest that vinylsulfone supplementation is a potential therapy for diabetes-associated neurodevelopmental defects. PMID- 26802112 TI - Cost Analysis of Motivational Interviewing and Preschool Education for Secondhand Smoke Exposures. AB - INTRODUCTION: This study determines if expenditures associated with implementing a combined motivational interviewing (MI) and Head Start-level education program (MI+Education), as compared to education alone, yield cost savings to society. METHODS: Post hoc cost analyses were applied to a randomized controlled-trial of MI among predominantly African American, low-income caregivers of 330 Baltimore City Head Start students who reside with a smoker. The primary outcome was the cost savings of MI+Education from averted direct secondhand smoke exposure (SHSe) related acute healthcare events and inferred indirect costs (work days lost, transportation and reduction in cigarettes smoked). The net direction of savings was defined by the sum of averted direct and indirect costs of the MI+Education intervention at 3, 6 and 12 months, benchmarked against the Education alone cohort at the equivalent time periods. RESULTS: The costs saved by the MI+Education intervention, relative to Education alone, resulted in savings at solely the 12-month follow-up time point. Significant savings were appreciated from averted emergency department (ED) visits at 12 months ($4410; 95% simulation interval [SI]: $2241, $6626) for the MI+Education group. The total savings at 12 months ($2274; 95% SI: -3916, $8442) could not overcome additional program costs of implementing MI to Head Start-level education ($13 695; 95% SI: $11 250, $16 034). CONCLUSIONS: This study is the first to examine the cost of either intervention on SHSe-attributed pediatric healthcare costs from a population level relevant for federal and community decision makers. Intervention costs could not be offset by short-term savings but a trend towards positive savings was appreciated 1 year after implementation. IMPLICATIONS: Behavioral interventions are effective in reducing SHSe in children. However, many of these interventions are not implemented in community settings due to lack of resources and money. Behavioral strategies may be a cost-saving addition to the national initiatives to create smoke-free home environments. The long-term benefits of MI, as evidenced from cost savings from averted ED visits, appeared to show MI+Education to be a robust long-term strategy. The decrease of acute healthcare services at 12 months may be informative for policy decision makers seeking to allocate limited resources to reduce the usage of costly ED services and hospital readmissions. PMID- 26802113 TI - Does sex influence the diagnostic evaluation of autism spectrum disorder in adults? AB - It is unknown whether sex influences the diagnostic evaluation of autism spectrum disorder, or whether male and female adults within the spectrum have different symptom profiles. This study reports sex differences in clinical outcomes for 1244 adults (935 males and 309 females) referred for autism spectrum disorder assessment. Significantly, more males (72%) than females (66%) were diagnosed with an autism spectrum disorder of any subtype (x(2) = 4.09; p = 0.04). In high functioning autism spectrum disorder adults (IQ > 70; N = 827), there were no significant sex differences in severity of socio-communicative domain symptoms. Males had significantly more repetitive behaviours/restricted interests than females (p = 0.001, d = 0.3). A multivariate analysis of variance indicated a significant interaction between autism spectrum disorder subtype (full-autism spectrum disorder/partial-autism spectrum disorder) and sex: in full-autism spectrum disorder, males had more severe socio-communicative symptoms than females; for partial-autism spectrum disorder, the reverse was true. There were no sex differences in prevalence of co-morbid psychopathologies. Sex influenced diagnostic evaluation in a clinical sample of adults with suspected autism spectrum disorder. The sexes may present with different manifestations of the autism spectrum disorder phenotype and differences vary by diagnostic subtype. Understanding and awareness of adult female repetitive behaviours/restricted interests warrant attention and sex-specific diagnostic assessment tools may need to be considered. PMID- 26802114 TI - Stability of early risk assessment for autism spectrum disorder in preterm infants. AB - Stability and change in early autism spectrum disorder risk were examined in a cohort of 99 preterm infants (?34 weeks of gestation) using the Autism Observation Scale for Infants at 8 and 12 months and the Autism Diagnostic Observation Schedule-Toddler Module at 18 months. A total of 21 infants were identified at risk by the Autism Observation Scale for Infants at 8 months, and 9 were identified at risk at 12 months, including 4 children who were not previously identified. At 18 months, eight children were identified at risk for autism spectrum disorder using the Autism Diagnostic Observation Schedule-Toddler Module, only half of whom had been identified using the original Autism Observation Scale for Infants cutoffs. Results are discussed in relation to early trajectories of autism spectrum disorder risk among preterm infants as well as identifying social-communication deficiencies associated with the early preterm behavioral phenotype. PMID- 26802115 TI - Accurate Transposable Element Annotation Is Vital When Analyzing New Genome Assemblies. AB - Transposable elements (TEs) are mobile genetic elements with the ability to replicate themselves throughout the host genome. In some taxa TEs reach copy numbers in hundreds of thousands and can occupy more than half of the genome. The increasing number of reference genomes from nonmodel species has begun to outpace efforts to identify and annotate TE content and methods that are used vary significantly between projects. Here, we demonstrate variation that arises in TE annotations when less than optimal methods are used. We found that across a variety of taxa, the ability to accurately identify TEs based solely on homology decreased as the phylogenetic distance between the queried genome and a reference increased. Next we annotated repeats using homology alone, as is often the case in new genome analyses, and a combination of homology and de novo methods as well as an additional manual curation step. Reannotation using these methods identified a substantial number of new TE subfamilies in previously characterized genomes, recognized a higher proportion of the genome as repetitive, and decreased the average genetic distance within TE families, implying recent TE accumulation. Finally, these finding-increased recognition of younger TEs-were confirmed via an analysis of the postman butterfly (Heliconius melpomene). These observations imply that complete TE annotation relies on a combination of homology and de novo-based repeat identification, manual curation, and classification and that relying on simple, homology-based methods is insufficient to accurately describe the TE landscape of a newly sequenced genome. PMID- 26802116 TI - Attraction, Feeding Preference, and Performance of Spodoptera frugiperda Larvae (Lepidoptera: Noctuidae) Reared on Two Varieties of Maize. AB - The fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), is an economically important pest of maize and other crops in the Americas. Studies suggest that modern varieties of maize lost some of their natural defense mechanisms against herbivores during domestication and agricultural selection. In the present study, we evaluated the attraction, feeding preference (host fidelity and consumption rate), and performance of S. frugiperda larvae reared on hybrid (Pioneer P4063W) and landrace (Tuxpeno) varieties of maize. We also evaluated the damage caused by S. frugiperda to Pioneer and Tuxpeno maize plants in the field. We found that fifth-instar larvae were more attracted to Pioneer plants than to Tuxpeno plants in a Y-tube olfactometer. Additionally, the fall armyworm larvae showed more fidelity to Pioneer leaves than to Tuxpeno leaves. However, the larval consumption rate was similar for both types of maize plants. The life cycle of S. frugiperda was significantly longer when the larvae were reared on Tuxpeno leaves than on Pioneer leaves. In the field, the Pioneer variety was infested with more S. frugiperda larvae than the Tuxpeno variety. Thus, our results provide evidence that modern varieties of maize may have lost some of their defensive traits during selective breeding. PMID- 26802117 TI - Effect of Wheat Cultivars and Blends on the Oviposition and Larval Mortality of Cephus cinctus (Hymenoptera: Cephidae) and Parasitism by Bracon cephi (Hymenoptera: Braconidae). AB - The wheat stem sawfly (Cephus cinctus Norton) is a major historical pest of wheat in the northern Great Plains of North America. The insect spends most of its life as a larva protected inside grass stems so that its management has relied on strategies other than insecticides. We conducted a study in southern Alberta from 2006-2009 to assess the effects of wheat species, cultivar, seeding rate, and blending a resistant and a vulnerable cultivar, on oviposition, larval infestation, and cutting damage. The mortality caused by its primary parasitoid, Bracon cephi (Gahan), was also assessed to investigate the potential benefit of cultivar blends to enhance sawfly biological control. Sawfly laid fewer eggs on plants of the durum cultivar 'AC Avonlea' and on those of the solid-stemmed cultivar 'Lillian' compared to plants of the hollow-stemmed cultivar 'CDC Go.' Larval establishments (infestation) followed a similar pattern to that of oviposition. At these locations there was low cutting damage in most years and to a large extent this was due to mortality inflicted by the parasitoid Bracon cephi (40-60%). However, the remaining mortality was attributed to other factors and host, particularly the inclusion of the solid-stemmed cultivar. Direct and indirect factors likely affected the success of the parasitoid in the crop monocultures and blends, and these mechanisms require further research. PMID- 26802118 TI - Preventing Disruptive Behavior via Classroom Management: Validating the Color Wheel System in Kindergarten Classrooms. AB - Evidence suggests that installing a classroom management system known as the Color Wheel reduced inappropriate behaviors and increased on-task behavior in second- and fourth-grade classrooms; however, no systematic studies of the Color Wheel had been disseminated targeting pre-school or kindergarten participants. To enhance our understanding of the Color Wheel System (CWS) as a prevention system, a multiple-baseline design was used to evaluate the effects of the Color Wheel on inappropriate vocalizations (IVs) in three general education kindergarten classrooms. Partial-interval time-sampling was used to record classwide IVs, which were operationally defined as any comment or vocal noise that was not solicited by the teacher. Time series graphs and effect size calculations suggest that the CWS caused immediate, large, and sustained decreases in IVs across the three classrooms. Teacher acceptability and interview data also supported the CWS. Implications related to prevention are discussed and directions for future research are provided. PMID- 26802119 TI - Cystic fibrosis and the war for iron at the host-pathogen battlefront. PMID- 26802120 TI - Mode of action and resistance studies unveil new roles for tropodithietic acid as an anticancer agent and the gamma-glutamyl cycle as a proton sink. AB - While we have come to appreciate the architectural complexity of microbially synthesized secondary metabolites, far less attention has been paid to linking their structural features with possible modes of action. This is certainly the case with tropodithietic acid (TDA), a broad-spectrum antibiotic generated by marine bacteria that engage in dynamic symbioses with microscopic algae. TDA promotes algal health by killing unwanted marine pathogens; however, its mode of action (MoA) and significance for the survival of an algal-bacterial miniecosystem remains unknown. Using cytological profiling, we herein determine the MoA of TDA and surprisingly find that it acts by a mechanism similar to polyether antibiotics, which are structurally highly divergent. We show that like polyether drugs, TDA collapses the proton motive force by a proton antiport mechanism, in which extracellular protons are exchanged for cytoplasmic cations. The alpha-carboxy-tropone substructure is ideal for this purpose as the proton can be carried on the carboxyl group, whereas the basicity of the tropylium ion facilitates cation export. Based on similarities to polyether anticancer agents we have further examined TDA's cytotoxicity and find it to exhibit potent, broad spectrum anticancer activities. These results highlight the power of MoA profiling technologies in repurposing old drugs for new targets. In addition, we identify an operon that confers TDA resistance to the producing marine bacteria. Bioinformatic and biochemical analyses of these genes lead to a previously unknown metabolic link between TDA/acid resistance and the gamma-glutamyl cycle. The implications of this resistance mechanism in the context of the algal bacterial symbiosis are discussed. PMID- 26802121 TI - Recruitment of A20 by the C-terminal domain of NEMO suppresses NF-kappaB activation and autoinflammatory disease. AB - Receptor-induced NF-kappaB activation is controlled by NEMO, the NF-kappaB essential modulator. Hypomorphic NEMO mutations result in X-linked ectodermal dysplasia with anhidrosis and immunodeficiency, also referred to as NEMO syndrome. Here we describe a distinct group of patients with NEMO C-terminal deletion (DeltaCT-NEMO) mutations. Individuals harboring these mutations develop inflammatory skin and intestinal disease in addition to ectodermal dysplasia with anhidrosis and immunodeficiency. Both primary cells from these patients, as well as reconstituted cell lines with this deletion, exhibited increased IkappaB kinase (IKK) activity and production of proinflammatory cytokines. Unlike previously described loss-of-function mutations, DeltaCT-NEMO mutants promoted increased NF-kappaB activation in response to TNF and Toll-like receptor stimulation. Investigation of the underlying mechanisms revealed impaired interactions with A20, a negative regulator of NF-kappaB activation, leading to prolonged accumulation of K63-ubiquitinated RIP within the TNFR1 signaling complex. Recruitment of A20 to the C-terminal domain of NEMO represents a novel mechanism limiting NF-kappaB activation by NEMO, and its absence results in autoinflammatory disease. PMID- 26802122 TI - Chemotaxis toward phytoplankton drives organic matter partitioning among marine bacteria. AB - The microenvironment surrounding individual phytoplankton cells is often rich in dissolved organic matter (DOM), which can attract bacteria by chemotaxis. These "phycospheres" may be prominent sources of resource heterogeneity in the ocean, affecting the growth of bacterial populations and the fate of DOM. However, these effects remain poorly quantified due to a lack of quantitative ecological frameworks. Here, we used video microscopy to dissect with unprecedented resolution the chemotactic accumulation of marine bacteria around individual Chaetoceros affinis diatoms undergoing lysis. The observed spatiotemporal distribution of bacteria was used in a resource utilization model to map the conditions under which competition between different bacterial groups favors chemotaxis. The model predicts that chemotactic, copiotrophic populations outcompete nonmotile, oligotrophic populations during diatom blooms and bloom collapse conditions, resulting in an increase in the ratio of motile to nonmotile cells and in the succession of populations. Partitioning of DOM between the two populations is strongly dependent on the overall concentration of bacteria and the diffusivity of different DOM substances, and within each population, the growth benefit from phycospheres is experienced by only a small fraction of cells. By informing a DOM utilization model with highly resolved behavioral data, the hybrid approach used here represents a new path toward the elusive goal of predicting the consequences of microscale interactions in the ocean. PMID- 26802123 TI - Something "hairy" in juvenile hormone signaling for mosquito reproduction. PMID- 26802125 TI - Cell-cell communication during collective migration. PMID- 26802127 TI - Survey of the use of domperidone and the association with QTc prolongation in general practice. AB - PURPOSE OF THE STUDY: Domperidone is associated with QTc prolongation, predisposing to the development of ventricular arrhythmias. In 2014, The Medicines and Healthcare Regulatory Agency (MHRA) recommended restricting its use. We assessed whether these recommendations have been implemented in a general practice. STUDY DESIGN: We conducted a prospective study using the general practitioner (GP) computer database on patients who had at least one repeat prescription for domperidone in 12 months. Data were presented to the doctors and the survey was repeated 7 months later. RESULTS: Sixty-four patients (mean age 61.3+/-16.4 years) were identified who had received at least one repeat prescription of domperidone. Twenty patients were being prescribed over the recommended daily dose. Nineteen patients were coprescribed medications known to prolong the QTc interval and two CYP3A4 inhibitors. The repeat survey performed 7 months later demonstrated a 70% reduction in the number of patients prescribed domperidone to a total of 19 (three patients prescribed above the recommended dose) none of which had a history of cardiac disease or were being coprescribed drugs known to prolong the QTc interval. CONCLUSIONS: Following the publication of the MHRA recommendations and presentation of our initial survey, there has been a significant reduction in the number of patients treated with domperidone and those coprescribed drugs known to prolong the QTc interval. We suggest that regular review of GP practice database should be performed to identify those patients prescribed domperidone and at risk of life-threatening arrhythmias and measures taken to use alternative pharmacological agents. PMID- 26802126 TI - Polycomb inhibits histone acetylation by CBP by binding directly to its catalytic domain. AB - Drosophila Polycomb (PC), a subunit of Polycomb repressive complex 1 (PRC1), is well known for its role in maintaining repression of the homeotic genes and many others and for its binding to trimethylated histone H3 on Lys 27 (H3K27me3) via its chromodomain. Here, we identify a novel activity of PC: inhibition of the histone acetylation activity of CREB-binding protein (CBP). We show that PC and its mammalian CBX orthologs interact directly with the histone acetyltransferase (HAT) domain of CBP, binding to the previously identified autoregulatory loop, whose autoacetylation greatly enhances HAT activity. We identify a conserved PC motif adjacent to the chromodomain required for CBP binding and show that PC binding inhibits acetylation of histone H3. CBP autoacetylation impairs PC binding in vitro, and PC is preferentially associated with unacetylated CBP in vivo. PC knockdown elevates the acetylated H3K27 (H3K27ac) level globally and at promoter regions of some genes that are bound by both PC and CBP. Conversely, PC overexpression decreases the H3K27ac level in vivo and also suppresses CBP dependent Polycomb phenotypes caused by overexpression of Trithorax, an antagonist of Polycomb silencing. We find that PC is physically associated with the initiating form of RNA polymerase II (Pol II) and that many promoters co occupied by PC and CBP are associated with paused Pol II, suggesting that PC may play a role in Pol II pausing. These results suggest that PC/PRC1 inhibition of CBP HAT activity plays a role in regulating transcription of both repressed and active PC-regulated genes. PMID- 26802128 TI - Obstructive atelectasis of the lung. PMID- 26802124 TI - Metabolic stress is a barrier to Epstein-Barr virus-mediated B-cell immortalization. AB - Epstein-Barr virus (EBV) is an oncogenic herpesvirus that has been causally linked to the development of B-cell and epithelial malignancies. Early after infection, EBV induces a transient period of hyperproliferation that is suppressed by the activation of the DNA damage response and a G1/S-phase growth arrest. This growth arrest prevents long-term outgrowth of the majority of infected cells. We developed a method to isolate and characterize infected cells that arrest after this early burst of proliferation and integrated gene expression and metabolic profiling to gain a better understanding of the pathways that attenuate immortalization. We found that the arrested cells have a reduced level of mitochondrial respiration and a decrease in the expression of genes involved in the TCA cycle and oxidative phosphorylation. Indeed, the growth arrest in early infected cells could be rescued by supplementing the TCA cycle. Arrested cells were characterized by an increase in the expression of p53 pathway gene targets, including sestrins leading to activation of AMPK, a reduction in mTOR signaling, and, consequently, elevated autophagy that was important for cell survival. Autophagy was also critical to maintain early hyperproliferation during metabolic stress. Finally, in assessing the metabolic changes from early infection to long-term outgrowth, we found concomitant increases in glucose import and surface glucose transporter 1 (GLUT1) levels, leading to elevated glycolysis, oxidative phosphorylation, and suppression of basal autophagy. Our study demonstrates that oncogene-induced senescence triggered by a combination of metabolic and genotoxic stress acts as an intrinsic barrier to EBV-mediated transformation. PMID- 26802129 TI - Stereoselective Glucuronidation of Bupropion Metabolites In Vitro and In Vivo. AB - Bupropion is a widely used antidepressant and smoking cessation aid in addition to being one of two US Food and Drug Administration-recommended probe substrates for evaluation of cytochrome P450 2B6 activity. Racemic bupropion undergoes oxidative and reductive metabolism, producing a complex profile of pharmacologically active metabolites with relatively little known about the mechanisms underlying their elimination. A liquid chromatography-tandem mass spectrometry assay was developed to simultaneously separate and detect glucuronide metabolites of (R,R)- and (S,S)-hydroxybupropion, (R,R)- and (S,S) hydrobupropion (threo) and (S,R)- and (R,S)-hydrobupropion (erythro), in human urine and liver subcellular fractions to begin exploring mechanisms underlying enantioselective metabolism and elimination of bupropion metabolites. Human liver microsomal data revealed marked glucuronidation stereoselectivity [Cl(int), 11.4 versus 4.3 ul/min per milligram for the formation of (R,R)- and (S,S) hydroxybupropion glucuronide; and Cl(max), 7.7 versus 1.1 ul/min per milligram for the formation of (R,R)- and (S,S)-hydrobupropion glucuronide], in concurrence with observed enantioselective urinary elimination of bupropion glucuronide conjugates. Approximately 10% of the administered bupropion dose was recovered in the urine as metabolites with glucuronide metabolites, accounting for approximately 40%, 15%, and 7% of the total excreted hydroxybupropion, erythro hydrobupropion, and threo-hydrobupropion, respectively. Elimination pathways were further characterized using an expressed UDP-glucuronosyl transferase (UGT) panel with bupropion enantiomers (both individual and racemic) as substrates. UGT2B7 catalyzed the stereoselective formation of glucuronides of hydroxybupropion, (S,S)-hydrobupropion, (S,R)- and (R,S)-hydrobupropion; UGT1A9 catalyzed the formation of (R,R)-hydrobupropion glucuronide. These data systematically describe the metabolic pathways underlying bupropion metabolite disposition and significantly expand our knowledge of potential contributors to the interindividual and intraindividual variability in therapeutic and toxic effects of bupropion in humans. PMID- 26802131 TI - Conflicts of interest and the truth of scientific discovery: an editor's perspective. PMID- 26802130 TI - Simvastatin Hydroxy Acid Fails to Attain Sufficient Central Nervous System Tumor Exposure to Achieve a Cytotoxic Effect: Results of a Preclinical Cerebral Microdialysis Study. AB - 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors were potent hits against a mouse ependymoma cell line, but their effectiveness against central nervous system tumors will depend on their ability to cross the blood-brain barrier and attain a sufficient exposure at the tumor. Among 3-hydroxy-3 methylglutaryl coenzyme A inhibitors that had activity in vitro, we prioritized simvastatin (SV) as the lead compound for preclinical pharmacokinetic studies based on its potential for central nervous system penetration as determined from in silico models. Furthermore, we performed systemic plasma disposition and cerebral microdialysis studies of SV (100 mg/kg, p.o.) in a murine model of ependymoma to characterize plasma and tumor extracellular fluid (tECF) pharmacokinetic properties. The murine dosage of SV (100 mg/kg, p.o.) was equivalent to the maximum tolerated dose in patients (7.5 mg/kg, p.o.) based on equivalent plasma exposure of simvastatin acid (SVA) between the two species. SV is rapidly metabolized in murine plasma with 15 times lower exposure compared with human plasma. SVA exposure in tECF was <33.8 +/- 11.9 ug/l per hour, whereas the tumor to plasma partition coefficient of SVA was <0.084 +/- 0.008. Compared with in vitro washout IC50 values, we did not achieve sufficient exposure of SVA in tECF to suggest tumor growth inhibition; therefore, SV was not carried forward in subsequent preclinical efficacy studies. PMID- 26802132 TI - A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. AB - AIMS: Sustained cardiac hypertrophy accompanied by maladaptive cardiac remodelling represents an early event in the clinical course leading to heart failure. Maladaptive hypertrophy is considered to be a therapeutic target for heart failure. However, the molecular mechanisms that regulate cardiac hypertrophy are largely unknown. METHODS AND RESULTS: Here we show that a circular RNA (circRNA), which we term heart-related circRNA (HRCR), acts as an endogenous miR-223 sponge to inhibit cardiac hypertrophy and heart failure. miR 223 transgenic mice developed cardiac hypertrophy and heart failure, whereas miR 223-deficient mice were protected from hypertrophic stimuli, indicating that miR 223 acts as a positive regulator of cardiac hypertrophy. We identified ARC as a miR-223 downstream target to mediate the function of miR-223 in cardiac hypertrophy. Apoptosis repressor with CARD domain transgenic mice showed reduced hypertrophic responses. Further, we found that a circRNA HRCR functions as an endogenous miR-223 sponge to sequester and inhibit miR-223 activity, which resulted in the increase of ARC expression. Heart-related circRNA directly bound to miR-223 in cytoplasm and enforced expression of HRCR in cardiomyocytes and in mice both exhibited attenuated hypertrophic responses. CONCLUSIONS: These findings disclose a novel regulatory pathway that is composed of HRCR, miR-223, and ARC. Modulation of their levels provides an attractive therapeutic target for the treatment of cardiac hypertrophy and heart failure. PMID- 26802133 TI - The novel application of intraprocedural cardiac computed tomography for left atrial appendage occlusion. PMID- 26802134 TI - Percutaneous tricuspid valve therapies: the new frontier. AB - Moderate-to-severe tricuspid regurgitation (TR) affects ~1.6 million patients in the USA, of whom only 8000 undergo tricuspid surgery annually; this results in an extremely large number of untreated patients with significant TR. Therefore, there is a large unmet clinical need for patients with severe TR who are not referred for conventional surgery, mainly due to expected high surgical risk. Percutaneous procedures are an attractive alternative to surgery for patients deemed to be high-risk surgical candidates. Whereas over the past few years, the development and clinical use of percutaneous approaches to the aortic valve and mitral valve have been widespread, few data are available about the feasibility and the efficacy of the percutaneous tricuspid valve treatment. This review will explore the available technologies, which are today under evaluation and the preliminary clinical results. PMID- 26802135 TI - Molecular multimodality imaging: has a long-standing dream come true? PMID- 26802136 TI - Mechanical aortic valves and massive mitral calcifications should not preclude transcatheter mitral Valve-In-Ring TAVI device implantation. PMID- 26802137 TI - Malapposition: is it a major cause of stent thrombosis? PMID- 26802138 TI - The synthetic cannabinoid R(+)WIN55,212-2 augments interferon-beta expression via peroxisome proliferator-activated receptor-alpha. PMID- 26802140 TI - Long-term Protection After Hepatitis B Vaccine. PMID- 26802139 TI - Antibody Levels and Protection After Hepatitis B Vaccine: Results of a 30-Year Follow-up Study and Response to a Booster Dose. AB - BACKGROUND: The duration of protection in children and adults resulting from hepatitis B vaccination is unknown. In 1981, we immunized a cohort of 1578 Alaska Native adults and children from 15 Alaska communities aged >=6 months using 3 doses of plasma-derived hepatitis B vaccine. METHODS: Persons were tested for antibody to hepatitis B surface antigen (anti-HBs) levels 30 years after receiving the primary series. Those with levels <10 mIU/mL received 1 booster dose of recombinant hepatitis B vaccine 2-4 weeks later and were then evaluated on the basis of anti-HBs measurements 30 days after the booster. RESULTS: Among 243 persons (56%) who responded to the original primary series but received no subsequent doses during the 30-year period, 125 (51%) had an anti-HBs level >=10 mIU/mL. Among participants with anti-HBs levels <10 mIU/mL who were available for follow-up, 75 of 85 (88%) responded to a booster dose with an anti-HBs level >=10 mIU/mL at 30 days. Initial anti-HBs level after the primary series was correlated with higher anti-HBs levels at 30 years. CONCLUSIONS: Based on anti-HBs level >=10 mIU/mL at 30 years and an 88% booster dose response, we estimate that >=90% of participants had evidence of protection 30 years later. Booster doses are not needed. PMID- 26802141 TI - Complement Factor H Serum Levels Determine Resistance to Pneumococcal Invasive Disease. AB - Streptococcus pneumoniae is a major cause of life-threatening infections. Complement activation plays a vital role in opsonophagocytic killing of pneumococci in blood. Initial complement activation via the classical and lectin pathways is amplified through the alternative pathway amplification loop. Alternative pathway activity is inhibited by complement factor H (FH). Our study demonstrates the functional consequences of the variability in human serum FH levels on host defense. Using an in vivo mouse model combined with human in vitro assays, we show that the level of serum FH correlates with the efficacy of opsonophagocytic killing of pneumococci. In summary, we found that FH levels determine a delicate balance of alternative pathway activity, thus affecting the resistance to invasive pneumococcal disease. Our results suggest that variation in FH expression levels, naturally occurring in the human population, plays a thus far unrecognized role in the resistance to invasive pneumococcal disease. PMID- 26802142 TI - Helicobacter pylori Activates Matrix Metalloproteinase 10 in Gastric Epithelial Cells via EGFR and ERK-mediated Pathways. AB - Helicobacter pylori colonizes the human stomach and increases the risk for peptic ulcer disease and gastric carcinoma. H. pylori upregulates the expression and activity of several matrix metalloproteinases (MMPs) in cell lines and in the gastric mucosa. The aim of this study was to explore the mechanisms leading to upregulation of MMP10 in gastric epithelial cells induced by H. pylori Infection of gastric cells with H. pylori led to an increase in levels of MMP-10 messenger RNA, protein secretion, and activity. cagA knockout mutants or CagA phosphorylation-defective mutants failed to increase MMP10 expression. These results were confirmed in infection experiments with clinical isolates with known cagA status and in human gastric biopsy specimens. Treatment of cells with chemical inhibitors of the receptor tyrosine kinase EGFR and the kinase Src abrogated H. pylori-induced MMP10 expression. Inhibitors of ERK1/2 and JNK kinases abolished and significantly decreased H. pylori-induced MMP10 expression, respectively, whereas inhibition of the kinase p38 had no effect. Finally, inhibition of MMP10 expression by small interfering RNA led to a decrease in the gastric cell-invasive phenotype mediated by the infection. In conclusion, CagA positive H. pylori strains stimulate MMP10 expression. MMP-10 modulation occurs via EGFR activation in a process that involves Src, ERK, and JNK pathways. MMP-10 may be implicated in H. pylori-mediated extracellular matrix remodeling. PMID- 26802144 TI - The staging of malignant pleural mesothelioma: are we any nearer to squaring the circle? PMID- 26802143 TI - Specimen weight and volume: important predictors of survival in malignant pleural mesothelioma. AB - OBJECTIVES: The tumour/node/metastasis (TNM) staging system for malignant pleural mesothelioma (MPM) is a worldwide standard, but has many limitations. Tumour volume has been suggested as a predictor of survival. Due to the complex anatomy, estimation of tumour volume via CT scan can be challenging. Surgical volume may be more accurate. Therefore, we prospectively determined resected specimen volumes and weights in consecutive patients undergoing extended pleurectomy and decortication (EPD) and correlated this with overall survival and T and N stage. METHODS: We evaluated 116 patients undergoing EPD for MPM in a single university centre over a 6-year period. All resected specimens were weighed, and the volume was measured by a fluid displacement method. A Cox regression model was used to identify significant predictors of survival; hazard ratios were calculated. A Kaplan-Meier method was used to summarize overall and subgroup survival. Logistic regression models were used to identify predictors of T and N stage. RESULTS: There were 95 males and 21 females with a median age of 68 range 43-88 years. Forty-one patients had an ECOG performance status (PS) 0, 70 had 1 and 4 had 2. The median time between initial diagnosis and surgery was 134 days. Histology was epithelioid in 59, biphasic in 55 and sarcomatoid in 2. The mean volume was 641 ml with an SD of 393.34 ml. The median volume was 567.5 ml. The mean weight was 620.8 g with an SD of 361.92 g. The median weight was 552.0 g. Two-year survival from initial diagnosis and from EPD was 44 and 28%, respectively. PS (P = 0.002), epithelioid histology (P < 0.001), specimen weight (P < 0.001), volume (P < 0.001), platelet count (P = 0.015), T1 stage (P = 0.04) and adjuvant therapy (P = 01) were predictive of survival. Tumour volume was a predictor of T stage (P = 0.048) and survival (P = 0.03). There was no relationship between N stage and tumour volume, weight or histology. CONCLUSIONS: PS, specimen weight, volume, epithelioid histology platelet count and adjuvant chemotherapy are significant predictors of survival in patients undergoing EPD for MPM. There is a correlation between specimen volume and T stage. These data suggest that tumour weight and volume may be valuable components for staging MPM. PMID- 26802145 TI - Dysregulation of renal microRNA expression after deep hypothermic circulatory arrest in rats. AB - OBJECTIVES: Acute kidney injury (AKI) is a severe complication of cardiopulmonary bypass-deep hypothermic circulatory arrest (DHCA) surgery. Non-coding microRNAs (miRNAs) are considered as key players in kidney physiology and pathology. However, whether they are implicated in DHCA-induced AKI at the early stage post surgery is less studied, and requires for further investigation. METHODS: In this study, kidney tissues were removed at 2 h post-surgery from Sprague-Dawley rats that underwent a 60-min DHCA (18 degrees C), with samples from sham-operated rats as control. Renal RNA isolates were analysed with Affymetrix miRNA microarray 4.0 containing 728 mature rat miRNA probes. RESULTS: Seventy-one miRNAs were down regulated and 4 were up-regulated in the kidneys of DHCA rats [log2 (fold change, FC) > 1, P < 0.05]. Novel differentially expressed miRNAs, such as miRNA-3068, miR-1949 and miR-3473, were identified in the injured kidney tissues. Putative target genes of the down-regulated miR-30b-5p, miR-199a-5p, miR-148b-3p and miR 10a-3p were subjected to analyses of gene ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results indicated that these miRNAs targeted a large set of genes involved in essential biological processes related to AKI pathogenesis, such as apoptotic process and response to hypoxia, as well as genes implicated in critical signalling pathways, such as chemokine, lysosome and FoxO signalling pathways (false discovery rate-corrected, P < 0.05). CONCLUSIONS: The identified 75 differentially expressed miRNAs hold the potential to serve as novel early markers and novel therapeutic targets for DHCA-AKI. PMID- 26802146 TI - Novel compound heterozygous mutation in the CNGA1 gene underlie autosomal recessive retinitis pigmentosa in a Chinese family. AB - Retinitis pigmentosa (RP) describes a group of inherited retinopathies that are characterized by the progressive degeneration of photoreceptor neurons, which causes night blindness, a reduction in the peripheral visual field and decreased visual acuity. More than 50 RP-related genes have been identified. In the present study, we analysed a Chinese family with autosomal recessive RP. We identified a compound heterozygous mutation, c.265delC and c.1537G>A, in CNGA1 using targeted next-generation sequencing (NGS) of RP-causing genes. The mutations were validated in the family members by Sanger sequencing. The mutations co-segregated with the RP phenotype and were absent from ethnically-matched control chromosomes. The mutant (mut) CNGA1 p.(G513R) protein caused by the mis-sense novel mutation c.1537G>A was expressed in vitro. The mut CNGA1 p.(G513R) protein was largely retained inside the cell rather than being targeted to the plasma membrane, suggesting the absence of cGMP-gated cation channels in the plasma membrane would be deleterious to rod photoreceptors, leading lead to RP. PMID- 26802147 TI - A randomized, double-blind, placebo-controlled phase II study to assess the efficacy and safety of mapatumumab with sorafenib in patients with advanced hepatocellular carcinoma. AB - BACKGROUND: This randomized, double-blind, placebo-controlled, phase II study evaluated the efficacy and safety of mapatumumab (a human agonistic monoclonal antibody against tumor necrosis factor-related apoptosis-inducing ligand receptor 1) in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients with advanced HCC (stratified by Barcelona Clinic Liver Cancer stage and Eastern Cooperative Oncology Group performance status) were randomized 1:1 to receive sorafenib (400 mg, twice daily per 21-day cycle) and either placebo (placebo-sorafenib arm) or mapatumumab (30 mg/kg on day 1 per 21-day cycle; mapatumumab-sorafenib arm). The primary end point was time to (radiologic) progression (TTP), assessed by blinded independent central review. Key secondary end points included progression-free survival, overall survival, and objective response. RESULTS: In total, 101 patients were randomized (placebo-sorafenib arm: N = 51; mapatumumab-sorafenib arm: N = 50). There was no significant difference in median TTP between both arms [5.6 versus 4.1 months, respectively; adjusted hazard ratio (one-sided 90% confidence interval) 1.192 (0-1.737)]. No mapatumumab-related benefit was identified when TTP was evaluated in the stratified subgroups. The addition of mapatumumab to sorafenib did not demonstrate improvement in the secondary efficacy end points. The reported frequency of adverse events (AEs) and serious AEs was comparable in both treatment arms. CONCLUSIONS: The addition of mapatumumab to sorafenib did not improve TTP or other efficacy end points, nor did it substantially change the toxicity profile of sorafenib in patients with advanced HCC. Based on these results, further development of the combination of mapatumumab and sorafenib in HCC is not planned. PMID- 26802148 TI - Breakthrough therapies in B-cell non-Hodgkin lymphoma. AB - The last 5 years have seen significant advances in our understanding of the molecular pathogenesis of B-cell lymphomas. This has led to the emergence of a large number of new therapeutic agents exploiting precise aspects of the tumor cell's signaling pathways, surface antigens or microenvironment. The purpose of this comprehensive review is to provide a detailed analysis of the breakthrough agents in the field, with a focus on recent clinical data. We describe agents targeting the B-cell receptor pathway, Bcl-2 inhibitors, emerging epigenetic therapies, new monoclonal antibodies and antibody drug conjugates, selective inhibitors of nuclear export, agents targeting the programmed cell death axis and chimeric antigen receptor T cells. PMID- 26802150 TI - Extranodal extension is an important prognostic parameter for both colonic and rectal cancer. PMID- 26802149 TI - Clinical correlation of extensive-stage small-cell lung cancer genomics. AB - BACKGROUND: Genomic studies in small-cell lung cancer (SCLC) lag far behind those carried out in nonsmall-cell lung cancer (NSCLC). To date, most SCLC studies have evaluated patients with surgically resectable disease. Here we sought to evaluate the genomic mutation spectrum of 'every-day' SCLC patient tumors with extensive stage disease (ES-SCLC) and to correlate mutations with the main clinical outcomes of response to chemotherapy, progression-free (PFS) and overall (OS) survival. PATIENTS AND METHODS: A total of 50 SCLC patient tumors were examined in this study; targeted exome sequencing was obtained on 42 patients and whole exome sequencing on 8 patients. Mutated genes were correlated with clinical outcomes using Kaplan-Meier methods (PFS, OS) and logistic regression (chemo response). RB1 protein expression was detected by either western blotting of cultured cell lysates or immunohistochemistry of tumor specimens. RESULTS: In all, 39 patients had ES-SCLC; 15 patients had either primary refractory/resistant disease and 21 patients had sensitive disease. The two most frequently mutated genes were TP53 (86%) and RB1 (58%); other frequently mutated genes (>10% patients) were involved in epigenetic regulation as well as the mTOR pathway. We identified a number of low-frequency, targetable mutations, including RICTOR, FGFR1, KIT, PTCH1 and RET. Using multivariate analysis, RB1 was the only significant factor (P = 0.038) in predicting response to first-line chemotherapy, with an odds ratio of 5.58 comparing mutant RB1 with wild-type. Patients with mutant RB1 had both better OS (11.7 versus 9.1 months P = 0.04) and PFS (11.2 versus 8.6 months, P = 0.06) compared with patients with wild-type RB1. Interestingly, ~25% of SCLC cell lines and tumor specimens expressed RB1 protein, possibly representing the subgroup with wild-type RB1. CONCLUSIONS: We found that SCLC tumors harboring no mutation in RB1 had a poor response to chemotherapy. PMID- 26802151 TI - Factors influencing outcome in advanced stage, low-grade follicular lymphoma treated at MD Anderson Cancer Center in the rituximab era. AB - BACKGROUND: The optimal initial therapy of follicular lymphoma (FL) remains unclear. The aims of this study were to compare primary treatment strategies and assess the impact of maintenance rituximab and patterns of treatment failure. PATIENTS AND METHODS: We retrospectively analyzed patients with treatment-naive advanced stage, grade 1-2 FL treated at our center from 2004 to 2014. We included 356 patients treated on clinical trials or standard of care with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP, n = 119); R CHOP with maintenance (R-CHOP + M, n = 65); bendamustine/rituximab (BR, n = 45); BR with maintenance (BR + M, n = 35); R(2) (n = 94). We compared baseline characteristics, progression-free survival (PFS), overall survival (OS) and analyzed prognostic factors using univariate and multivariate analysis adjusted for treatment. RESULTS: After a median follow-up of 4 years (range 0.2-15.0), the 3-year PFS was 60% [95% confidence interval (CI) 51% to 69%] for R-CHOP, 72% (59% to 82%) for R-CHOP + M, 63% (42% to 78%) for BR, 97% (80% to 100%) for BR + M and 87% (78% to 93%) for R(2). Patients treated with R-chemotherapy had more high risk features than patients treated with R(2) but, by adjusted multivariate analysis, treatment with R(2) [hazard ratio (HR) 0.39 (0.17-0.89), P = 0.02] was associated with a superior PFS. Eastern Cooperative Oncology Group Performance status of one or more predicted inferior OS. Among patients treated with R chemotherapy, maintenance was associated with the superior PFS [HR 0.38 (95% CI 0.21-0.68)]. By adjusted multivariate analysis, disease progression within 2 years [HR 5.1 (95% CI 1.57-16.83)] and histologic transformation (HT) [HR 11.05 (95% CI 2.84-42.93)] increased risk of death. CONCLUSION: Induction therapy with R(2) may result in disease control which is comparable with R-chemotherapy. Early disease progression and HT are predictive of inferior survival. PMID- 26802154 TI - HER2 imaging in the ZEPHIR study. PMID- 26802153 TI - Positron emission tomography response evaluation from a randomized phase III trial of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone for patients with metastatic adenocarcinoma of the pancreas. AB - BACKGROUND: In the phase III MPACT trial, nab-paclitaxel plus gemcitabine (nab-P + Gem) demonstrated superior efficacy versus Gem alone for patients with metastatic pancreatic cancer. We sought to examine the feasibility of positron emission tomography (PET) and to compare metabolic response rates and associated correlations with efficacy in the MPACT trial. PATIENTS AND METHODS: Patients with previously untreated metastatic adenocarcinoma of the pancreas were randomized 1:1 to receive nab-P + Gem or Gem alone. Treatment continued until disease progression by RECIST or unacceptable toxicity. RESULTS: PET scans were carried out on the first 257 patients enrolled at PET-equipped centers (PET cohort). Most patients (252 of 257) had >=2 PET-avid lesions, and median maximum standardized uptake values at baseline were 4.6 and 4.5 in the nab-P + Gem and Gem-alone arms, respectively. In a pooled treatment arm analysis, a metabolic response by PET (best response at any time during study) was associated with longer overall survival (OS) (median 11.3 versus 6.9 months; HR, 0.56; P < 0.001). Efficacy results within each treatment arm appeared better for patients with a metabolic response. The metabolic response rate (best response and week 8 response) was higher for nab-P + Gem (best response: 72% versus 53%, P = 0.002; week 8: 67% versus 51%; P = 0.014). Efficacy in the PET cohort was greater for nab-P + Gem versus Gem alone, including for OS (median 10.5 versus 8.4 months; hazard ratio [HR], 0.71; P = 0.009) and ORR by RECIST (31% versus 11%; P < 0.001). CONCLUSION: Pancreatic lesions were PET avid at baseline, and the rate of metabolic response was significantly higher for nab-P + Gem versus Gem alone at week 8 and for best response during study. Having a metabolic response was associated with longer survival, and more patients experienced a metabolic response than a RECIST-defined response. CLINICALTRIALSGOV: NCT00844649. PMID- 26802152 TI - New drugs in acute myeloid leukemia. AB - The standard therapy for acute myeloid leukemia (AML) has not changed meaningfully for the past four decades. Improvements in supportive care and modifications to the dose and schedule of existing agents have led to steady improvements in outcomes. However, developing new therapies for AML has been challenging. Although there have been advances in understanding the biology of AML, translating this knowledge to viable treatments has been slow. Active research is currently ongoing to address this important need and several promising drug candidates are currently in the pipeline. Here, we review some of the most advanced and promising compounds that are currently in clinical trials and may have the potential to be part of our future armamentarium. These drug candidates range from cytotoxic chemotherapies, targeted small-molecule inhibitors, and monoclonal antibodies. PMID- 26802155 TI - Selumetinib with and without erlotinib in KRAS mutant and KRAS wild-type advanced nonsmall-cell lung cancer. AB - BACKGROUND: KRAS mutations in NSCLC are associated with a lack of response to epidermal growth factor receptor inhibitors. Selumetinib (AZD6244; ARRY-142886) is an oral selective MEK kinase inhibitor of the Ras/Raf/MEK/ERK pathway. PATIENTS AND METHODS: Advanced nonsmall-cell lung cancer (NSCLC) patients failing one to two prior regimens underwent KRAS profiling. KRAS wild-type patients were randomized to erlotinib (150 mg daily) or a combination of selumetinib (150 mg daily) with erlotinib (100 mg daily). KRAS mutant patients were randomized to selumetinib (75 mg b.i.d.) or the combination. The primary end points were progression-free survival (PFS) for the KRAS wild-type cohort and objective response rate (ORR) for the KRAS mutant cohort. Biomarker studies of ERK phosphorylation and immune subsets were carried out. RESULTS: From March 2010 to May 2013, 89 patients were screened; 41 KRAS mutant and 38 KRAS wild-type patients were enrolled. Median PFS in the KRAS wild-type arm was 2.4 months [95% confidence interval (CI) 1.3-3.7] for erlotinib alone and 2.1 months (95% CI 1.8 5.1) for the combination. The ORR in the KRAS mutant group was 0% (95% CI 0.0% to 33.6%) for selumetinib alone and 10% (95% CI 2.1% to 26.3%) for the combination. Combination therapy resulted in increased toxicities, requiring dose reductions (56%) and discontinuation (8%). Programmed cell death-1 expression on regulatory T cells (Tregs), Tim-3 on CD8+ T cells and Th17 levels were associated with PFS and overall survival in patients receiving selumetinib. CONCLUSIONS: This study failed to show improvement in ORR or PFS with combination therapy of selumetinib and erlotinib over monotherapy in KRAS mutant and KRAS wild-type advanced NSCLC. The association of immune subsets and immune checkpoint receptor expression with selumetinib may warrant further studies. PMID- 26802157 TI - The global decrease in cancer mortality: trends and disparities. AB - BACKGROUND: A decrease in cancer mortality has been reported in the United States, Europe, and other high-income regions during the last two decades. Whether similar trends apply to low-to-middle income countries-and globally-is unclear. DESIGN: The aim of this descriptive study is to compare cancer mortality in all countries with high- or intermediate-quality data on death certificates according to the World Health Organization (WHO) mortality database for the years 2000 through 2010. We included 60 countries in the analysis and calculated age adjusted mortality rates for all cancer combined and for the commonest cancers worldwide: lung, stomach, breast, colorectal, uterine, and prostate. RESULTS: A decrease in overall cancer mortality rate of ~1% per year was observed in higher and lower income regions and in both sexes. In 2010, 696 000 cancer deaths were avoided on a global scale compared with 2000 rates (426 000 in men, 271 000 in women). However, the mortality of liver cancer in both sexes and lung cancer in females increased in many countries'. CONCLUSIONS: The individual risk of dying from cancer decreased in all countries with reliable data. This decrease was chiefly due to favorable trends in the commonest specific cancers. Liver cancer in both sexes and lung cancer in women, which show increasing mortality rates, constitute a priority for prevention and further research. PMID- 26802156 TI - A randomized, double-blind phase II study evaluating cediranib versus cediranib and saracatinib in patients with relapsed metastatic clear-cell renal cancer (COSAK). AB - BACKGROUND: Preclinical work suggests SRC proteins have a role in the development of resistance to vascular endothelial growth factor (VEGF) targeted therapy in metastatic clear-cell renal cancer (mRCC). This hypothesis was tested in this trial using the SRC inhibitor saracatinib and the VEGF inhibitor cediranib. PATIENTS AND METHODS: Patients with disease progression after >=1 VEGF-targeted therapy were eligible to participate in this double-blind, randomized (1:1) phase II study. The study compared the combination cediranib 30 mg once daily (o.d.) and saracatinib 175 mg o.d. (CS) (n = 69) or cediranib 45 mg o.d. and placebo o.d. (C) (n = 69). Archived tissue was used for biomarker analysis [SRC, focal adhesion kinase (FAK), von Hippel-Lindau, protein tyrosine phosphatase 1b and hypoxia-inducible factor 2alpha : n = 86]. The primary end point was progression free survival (PFS) by RECIST v1.1. RESULTS: Between 2010 and 2012, 138 patients were randomized across 16 UK sites. The characteristics of the two groups were well balanced. Partial responses were seen in 13.0% for C and 14.5% for CS (P > 0.05). There was no significant difference in PFS [5.4 months (3.6-7.3 months) for C and 3.9 (2.4-5.3 months) for CS; hazard ratio (HR) 1.18 (0.94-1.48)] or overall survival (OS) [14.2 months (11.2-16.8 months) for C and 10.0 (6.7-13.2 months) for CS; HR 1.28 (1.00-1.63)]. There was no significant difference in the frequency of key adverse events, dose reductions or drug discontinuations. None of the biomarkers were prognostic for PFS or OS. FAK overexpression correlated with an OS benefit [HR 2.29 (1.09-4.82), P > 0.05], but not PFS, for CS. CONCLUSIONS: Saracatinib did not increase the efficacy of a VEGF-targeted therapy (cediranib) in this setting. Biomarker analysis did not identify consistent predictive biomarkers. CLINICALTRIALSGOV: NCT00942877. PMID- 26802158 TI - Prognostic impact of extracapsular lymph node involvement in colorectal cancer. PMID- 26802159 TI - Reply to the letter to the editor 'Many men with castrate-sensitive metastatic prostate cancer should not receive chemotherapy' by Tannock et al. PMID- 26802161 TI - Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab. AB - BACKGROUND: Clinical responses to ipilimumab are variable in terms of onset, magnitude and duration. Upfront identification of patients who are more likely or unlikely to benefit from treatment is a major need. PATIENTS AND METHODS: Prospectively collected data from 720 advanced melanoma patients treated with ipilimumab 3 mg/kg within the Italian expanded access program were analyzed. The derived neutrophil-to-lymphocyte ratio (dNLR) was calculated from baseline peripheral blood cell counts, and receiver operating characteristic curve was used to evaluate the best cutoff for this marker. Patients were stratified according to dichotomized baseline absolute neutrophil counts (ANC), dNLR and their combination. The prognostic values of ANC and dNLR for survival were assessed using multivariate Cox proportional hazard models. A subgroup analysis including LDH in the models was also carried out. RESULTS: The median follow-up was 16.5 months. The optimal cutoff for dNLR was 3. Baseline ANC and dNLR were significantly associated with the outcome of ipilimumab-treated melanoma patients, in terms of disease progression and death (P < 0.0001 for all). Furthermore, for each elevated variable, prognosis worsened. Patients with both ANC >= 7500 and dNLR >= 3 had a significantly and independently increased risk of death [hazard ratio(HR) = 5.76; 95% confidence interval (CI) 4.29-7.75] and of progression (HR = 4.10; 95% CI 3.08-5.46) compared with patients with both lower ANC and dNLR. Patients with one of the two factors elevated displayed an intermediate risk of progression and death. The 1- and 2-year survival rates were 2% and 0%, respectively, for patients with ANC >= 7500 and dNLR >= 3, and 43% and 24%, respectively, for patients with both lower ANC and dNLR. CONCLUSIONS: Although these findings need to be confirmed and validated, we suggest that a neutrophil-based index may help risk-group stratification and assist disease management strategies. Furthermore, the potential predictive value of this index for response to ipilimumab should be investigated in randomized clinical trials. PMID- 26802162 TI - Phosphoproteomics in translational research: a sarcoma perspective. AB - Phosphoproteomics has been extensively used as a preclinical research tool to characterize the phosphorylated components of the cancer proteome. Advances in the field have yielded insights into new drug targets, mechanisms of disease progression and drug resistance, and biomarker discovery. However, application of this technology to clinical research has been challenging because of practical issues relating to specimen integrity and tumour heterogeneity. Beyond these limitations, phosphoproteomics has the potential to play a pivotal role in translational studies and contribute to advances in different tumour groups, including rare disease sites like sarcoma. In this review, we propose that deploying phosphoproteomic technologies in translational research may facilitate the identification of better defined predictive biomarkers for patient stratification, inform drug selection in umbrella trials and identify new combinations to overcome drug resistance. We provide an overview of current phosphoproteomic technologies, such as affinity-based assays and mass spectrometry-based approaches, and discuss their advantages and limitations. We use sarcoma as an example to illustrate the current challenges in evaluating targeted kinase therapies in clinical trials. We then highlight useful lessons from preclinical studies in sarcoma biology to demonstrate how phosphoproteomics may address some of these challenges. Finally, we conclude by offering a perspective and list the key measures required to translate and benchmark a largely preclinical technology into a useful tool for translational research. PMID- 26802160 TI - CA19-9 decrease at 8 weeks as a predictor of overall survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic pancreatic cancer. AB - BACKGROUND: A phase I/II study and subsequent phase III study (MPACT) reported significant correlations between CA19-9 decreases and prolonged overall survival (OS) with nab-paclitaxel plus gemcitabine (nab-P + Gem) treatment for metastatic pancreatic cancer (MPC). CA19-9 changes at week 8 and potential associations with efficacy were investigated as part of an exploratory analysis in the MPACT trial. PATIENTS AND METHODS: Untreated patients with MPC (N = 861) received nab-P + Gem or Gem alone. CA19-9 was evaluated at baseline and every 8 weeks. RESULTS: Patients with baseline and week-8 CA19-9 measurements were analyzed (nab-P + Gem: 252; Gem: 202). In an analysis pooling the treatments, patients with any CA19-9 decline (80%) versus those without (20%) had improved OS (median 11.1 versus 8.0 months; P = 0.005). In the nab-P + Gem arm, patients with (n = 206) versus without (n = 46) any CA19-9 decrease at week 8 had a confirmed overall response rate (ORR) of 40% versus 13%, and a median OS of 13.2 versus 8.3 months (P = 0.001), respectively. In the Gem-alone arm, patients with (n = 159) versus without (n = 43) CA19-9 decrease at week 8 had a confirmed ORR of 15% versus 5%, and a median OS of 9.4 versus 7.1 months (P = 0.404), respectively. In the nab-P + Gem and Gem-alone arms, by week 8, 16% (40/252) and 6% (13/202) of patients, respectively, had an unconfirmed radiologic response (median OS 13.7 and 14.7 months, respectively), and 79% and 84% of patients, respectively, had stable disease (SD) (median OS 11.1 and 9 months, respectively). Patients with SD and any CA19-9 decrease (158/199 and 133/170) had a median OS of 13.2 and 9.4 months, respectively. CONCLUSION: This analysis demonstrated that, in patients with MPC, any CA19-9 decrease at week 8 can be an early marker for chemotherapy efficacy, including in those patients with SD. CA19-9 decrease identified more patients with survival benefit than radiologic response by week 8. PMID- 26802163 TI - Selection and characterization of Anticalins targeting human prostate-specific membrane antigen (PSMA). AB - Although prostate carcinoma (PCa) is by far the most commonly diagnosed neoplasia in men, corresponding diagnostic and therapeutic modalities have limited efficacy at present. Anticalins comprise a novel class of binding proteins based on a non immunoglobulin scaffold that can be engineered to specifically address molecular targets of interest. Here we report the selection and characterization of Anticalins that recognize human prostate-specific membrane antigen (PSMA), a membrane-tethered metallopeptidase constituting a disease-related target for imaging and therapy of PCa as well as solid malignancies in general. We used a randomized lipocalin library based on the human lipocalin 2 (Lcn2) scaffold together with phage display and ELISA screening to select PSMA-specific variants. Five Anticalin candidates from the original panning were expressed in Escherichia coli as soluble monomeric proteins, revealing affinities toward PSMA down to the low nanomolar range. Binding characteristics of the most promising candidate were further improved via affinity maturation by applying error-prone PCR followed by selection via phage display as well as bacterial surface display under more stringent conditions. In BIAcore measurements, the dissociation constant of the best Anticalin was determined as ~500 pM, with a substantially improved dissociation rate compared with the first-generation candidate. Finally, immunofluorescence microscopy revealed specific staining of PSMA-positive tumor cell lines while flow cytometric analysis confirmed the ability of the selected Anticalins to detect PSMA on live cells. Taken together, Anticalins resulting from this study offer a viable alternative to antibody-based PSMA binders for biomedical applications, including in vivo imaging of PCa or neovasculature of solid tumors. PMID- 26802164 TI - Circumferential resection margin positivity after preoperative chemoradiotherapy based on magnetic resonance imaging for locally advanced rectal cancer: implication of boost radiotherapy to the involved mesorectal fascia. AB - OBJECTIVE: To identify patients who are at a higher risk of pathologic circumferential resection margin involvement using preoperative magnetic resonance imaging. METHODS: Between October 2008 and November 2012, 165 patients with locally advanced rectal cancer (cT4 or cT3 with <2 mm distance from tumour to mesorectal fascia) who received preoperative chemoradiotherapy were analysed. The morphologic patterns on post-chemoradiotherapy magnetic resonance imaging were categorized into five patterns from Pattern A (most-likely negative pathologic circumferential resection margin) to Pattern E (most-likely positive pathologic circumferential resection margin). In addition, the location of mesorectal fascia involvement was classified as lateral, posterior and anterior. The diagnostic accuracy of the morphologic criteria was calculated using receiver operating characteristic curve analysis. RESULTS: Pathologic circumferential resection margin involvement was identified in 17 patients (10.3%). The diagnostic accuracy of predicting pathologic circumferential resection margin involvement was 0.73 using the five-scale magnetic resonance imaging pattern. The sensitivity, specificity, positive predictive value and negative predictive value for predicting pathologic circumferential resection margin involvement were 76.5, 65.5, 20.3 and 96.0%, respectively, when cut-off was set between Patterns C and D. On multivariate logistic regression, the magnetic resonance imaging patterns D and E (P= 0.005) and posterior or lateral mesorectal fascia involvement (P= 0.017) were independently associated with increased probability of pathologic circumferential resection margin involvement. The rate of pathologic circumferential resection margin involvement was 30.0% when the patient had Pattern D or E with posterior or lateral mesorectal fascia involvement. CONCLUSIONS: Patients who are at a higher risk of pathologic circumferential resection margin involvement can be identified using preoperative magnetic resonance imaging although the predictability is moderate. PMID- 26802165 TI - Reduced miR-215 expression predicts poor prognosis in patients with acute myeloid leukemia. AB - OBJECTIVE: Abnormal expression of microRNA-215 has been identified in a variety of solid cancers. However, little is known about the expression pattern of microRNA-215 in acute myeloid leukemia. This study was to investigate the status of microRNA-215 expression and further analyze its clinical significance in acute myeloid leukemia. METHODS: Real-time quantitative polymerase chain reaction assay was performed to evaluate the expression level of microRNA-215 in 113 patients with acute myeloid leukemia. Besides, the relationship between microRNA-215 levels and clinical and pathological factors was explored. RESULTS: Compared with the healthy individuals, microRNA-215 expression in acute myeloid leukemia patients was significantly down-regulated (P= 0.001). MicroRNA-215 low-expressed patients had higher white blood cells than microRNA-215 high-expressed patients (P= 0.014). The incidence of FLT3/ITD mutation in the patients with low microRNA 215 expression was significantly higher than those with high microRNA-215 expression (P= 0.025). MicroRNA-215 low-expressed patients had significantly shorter overall survival than microRNA-215 high-expressed patients in both non-M3 acute myeloid leukemia patients and cytogenetically normal patients (P= 0.017 and P= 0.044, respectively). Meanwhile, multivariate analysis confirmed the adverse prognostic value of microRNA-215 expression in acute myeloid leukemia patients with non-M3 subtypes. CONCLUSIONS: Our study demonstrates that reduced microRNA 215 expression is a common event and is associated with poor clinical outcome in acute myeloid leukemia. PMID- 26802166 TI - High dose radiotherapy with image-guided hypo-IMRT for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombi is more feasible and efficacious than conventional 3D-CRT. AB - OBJECTIVE: To compare the efficacies of conventional three-dimensional conformal radiotherapy and image-guided hypofractionated intensity-modulated radiotherapy treatments in advanced hepatocellular carcinoma patients with portal vein and/or inferior vena cava tumor thrombi. METHODS: A total of 118 hepatocellular carcinoma patients with portal vein and/or inferior vena cava tumor thrombi who received external beam radiation therapy focused on tumor thrombi and intrahepatic tumors were retrospectively reviewed. During the three-dimensional conformal radiotherapy treatments, a median total dose of 54 Gy with a conventional fraction (1.8-2.0 Gy/fx) was delivered. During the image-guided hypofractionated intensity-modulated radiotherapy treatments, a median total dose of 60 Gy with fractions of 2.5-4.0 Gy/fx was delivered. RESULTS: The median follow-up time was 11.8 months (range, 1.7-43.7 months). Higher radiation doses were delivered by image-guided hypofractionated intensity-modulated radiotherapy than by three-dimensional conformal radiotherapy (average dose 57.86 +/- 7.03 versus 50.88 +/- 6.60 Gy, P <= 0.001; average biological effective dose 72.35 +/- 9.62 versus 61.45 +/- 6.64 Gy, P < 0.001). A longer median survival was found with image-guided hypofractionated intensity-modulated radiotherapy than with three-dimensional conformal radiotherapy (15.47 versus 10.46 months, P = 0.005). Multivariate analysis showed that image-guided hypofractionated intensity modulated radiotherapy is a significant prognostic factor for overall survival. Toxicity was mild for both image-guided hypofractionated intensity-modulated radiotherapy and three-dimensional conformal radiotherapy. CONCLUSIONS: High dose radiotherapy delivered by image-guided hypofractionated intensity-modulated radiotherapy appears to be an effective treatment that provides a survival benefit without increasing severe toxicity in hepatocellular carcinoma patients with portal vein and/or inferior vena cava tumor thrombi. PMID- 26802167 TI - Linking social capital: a forgotten component of social capital. PMID- 26802168 TI - Association between maternal education and objectively measured physical activity and sedentary time in adolescents. AB - BACKGROUND: Investigating socioeconomic variation in physical activity (PA) and sedentary time is important as it may represent a pathway by which socioeconomic position (SEP) leads to ill health. Findings on the association between children's SEP and objectively assessed PA and/or sedentary time are mixed, and few studies have included international samples. OBJECTIVE: Examine the associations between maternal education and adolescent's objectively assessed PA and sedentary time. METHODS: This is an observational study of 12 770 adolescents (10-18 years) pooled from 10 studies from Europe, Australia, Brazil and the USA. Original PA data were collected between 1997 and 2009. The associations between maternal education and accelerometer variables were examined using robust multivariable regression, adjusted for a priori confounders (ie, body mass index, monitor wear time, season, age and sex) and regression coefficients combined across studies using random effects meta-analyses. Analyses were conducted in March 2014. RESULTS: Adolescents of university educated mothers spent more time sedentary (9.5 min/day, p=0.005) and less time in light activity (10 min/day, p<0.001) compared with adolescents of high school educated mothers. Pooled analysis across two studies from Brazil and Portugal (analysed separately because of the different coding of maternal education) showed that children of higher educated mothers (tertiary vs primary/secondary) spent less time in moderate to vigorous PA (MVPA) (6.6 min/day, p=0.001) and in light PA (39.2 min/day: p<0.001), and more time sedentary (45.9 min/day, p<0.001). CONCLUSIONS: Across a number of international samples, adolescents of mothers with lower education may not be at a disadvantage in terms of overall objectively measured PA. PMID- 26802170 TI - Parasitism and Suitability of Fertilized and Nonfertilized Eggs of the Rice Striped Stem Borer, Chilo suppressalis (Lepidoptera: Crambidae), for Trichogramma Parasitoids. AB - Trichogramma spp. are egg parasitoids largely used worldwide for biological control of lepidopteran pests. Host quality (related to host size and age, host species, etc.) can influence parasitism preference and fitness of the parasitoid offspring. However, few studies have documented the performance of Trichogramma parasitoids when they parasitize nonfertilized eggs of their lepidopteran hosts. In the present study, we investigated the performance of three indigenous Trichogramma species ( Trichogramma japonicum Ashmead, Trichogramma dendrolimi Matsumura, and Trichogramma chilonis Ishii) on fertilized and nonfertilized eggs of their native host, Chilo suppressalis (Walker). The results showed that the three Trichogramma species tested could recognize fertilized and nonfertilized eggs of C. suppressalis . The different fertilization status eggs of C. suppressalis were all accepted by T. japonicum , T. chilonis , and T. dendrolimi with a clear tendency that they preferred to parasitize fertilized eggs whether under no-choice or choice conditions. All Trichogramma species successfully completed development in parasitized eggs of C. suppressalis regardless if the host eggs were fertilized or not. There was similar adult emergence rate, development time, and female progeny between fertilized and nonfertilized eggs for all Trichogramma species with an exception of development for T. chilonis . Trichogramma chilonis had shorter developmental time in fertilized eggs than in nonfertilized ones. Whether in fertilized or nonfertilized eggs, T. dendrolimi had longer development time than other two Trichogramma species. However, T. dendrolimi had the largest percentage of female progeny on fertilized eggs, followed by T. japonicum , and T. chilonis had the least percentage of female progeny. The present study indicates that Trichogramma parasitoids (i) can distinguish fertilized vs. nonfertilized host eggs, and (ii) could use nonfertilized host eggs for successful offspring development (despite showing lower preference for such eggs) [corrected]. PMID- 26802169 TI - Global molecular analysis and APOE mutations in a cohort of autosomal dominant hypercholesterolemia patients in France. AB - Autosomal dominant hypercholesterolemia (ADH) is a human disorder characterized phenotypically by isolated high-cholesterol levels. Mutations in the low density lipoprotein receptor (LDLR), APOB, and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes are well known to be associated with the disease. To characterize the genetic background associated with ADH in France, the three ADH associated genes were sequenced in a cohort of 120 children and 109 adult patients. Fifty-one percent of the cohort had a possible deleterious variant in LDLR, 3.1% in APOB, and 1.7% in PCSK9. We identified 18 new variants in LDLR and 2 in PCSK9. Three LDLR variants, including two newly identified, were studied by minigene reporter assay confirming the predicted effects on splicing. Additionally, as recently an in-frame deletion in the APOE gene was found to be linked to ADH, the sequencing of this latter gene was performed in patients without a deleterious variant in the three former genes. An APOE variant was identified in three patients with isolated severe hypercholesterolemia giving a frequency of 1.3% in the cohort. Therefore, even though LDLR mutations are the major cause of ADH with a large mutation spectrum, APOE variants were found to be significantly associated with the disease. Furthermore, using structural analysis and modeling, the identified APOE sequence changes were predicted to impact protein function. PMID- 26802171 TI - Can Subclinical Infestation by Paralyzing Dermacentor andersoni (Acari: Ixodidae) Induce Immunity to Tick Paralysis in Sheep? AB - Cattle and sheep can develop immunity to paralysis caused by Dermacentor andersoni Stiles; however, this has been reported only in animals that were initially challenged with a high dose of ticks and exhibited clear symptoms of paralysis. Paralysis in sheep occurs in a dose-dependent fashion, with no paralysis occurring in sheep exposed to <0.2 ticks per kilogram sheep weight, and 100% paralysis in sheep exposed to >0.8 ticks per kilogram. This experiment was conducted to determine if sheep exposed to a low dose of ticks would also develop immunity to paralysis. Sheep were exposed to either a low (0.2 ticks per kilogram) or high dose of ticks (0.8 ticks per kilogram), then re-exposed to a second challenge of a paralyzing dose of ticks. All naive sheep (eight of the eight) were paralyzed, while paralysis occurred in only four of the eight sheep previously exposed to a low dose, and one of the eight sheep previously exposed to a high dose. Results indicate that immunity can develop when sheep are exposed to a subclinical dose of paralyzing ticks, but in a smaller percentage of animals than those exposed to a high dose of ticks. Vaccine development perhaps remains the best option for nonacaricidal control of tick paralysis. PMID- 26802173 TI - Characterising the phenotype and progression of sporadic adult-onset foveomacular vitelliform dystrophy. AB - BACKGROUND/AIMS: Adult-onset foveomacular vitelliform dystrophy (AFVD) is a relatively common macular degeneration which might lead to substantial visual loss. Our purpose was to describe the natural course of genetically evaluated patients with sporadic AFVD. METHODS: A retrospective, consecutive, cohort study included 95 eyes of 51 patients. Mutations in genes previously associated with AFVD (PRPH2, BEST1, IMPG-1 and IMPG-2) were evaluated. Demographics, clinical characteristics, and spectral domain optical coherence tomography features were analysed. Main outcome measures were changes in the best corrected visual acuity (BCVA) and lesion morphology during the follow-up. RESULTS: The mean age (+/-SD) at diagnosis was 73.8+/-10.7 years. Mean (+/-SD) follow-up period was 30.4+/-16.3 months (range 0-44 months; median 25 months). All patients were genotyped negative for the evaluated mutations. Fifty-three of the eyes were followed for at least 36 months. At baseline these eyes had a mean BCVA (+/-SD) of 0.27+/-0.35 LogMAR, and at 36-months BCVA decreased to 0.38+/-0.35 (p=0.02). At baseline, 23 of these 53 eyes (43.4%) had the vitelliform stage, while only 10 eyes (18.9%) remained at this stage at 36 months (p=0.01). Ellipsoid zone alterations progressed during the follow-up (n=53 eyes) and showed correlation with BCVA reduction (Pearson's correlation coefficient=0.7, p=0.03). CONCLUSIONS: Sporadic AFVD is a slowly progressing macular degeneration of older people. It is associated with visual decline at the rate of approximately one ETDRS line during 3 years. Patients with sporadic AFVD are usually negative for the known mutations previously associated with this phenotype, and present at an age that is higher than described for monogenic AFVD. PMID- 26802172 TI - In situ stable isotope probing of phosphate-solubilizing bacteria in the hyphosphere. AB - This study used a [(13)C]DNA stable isotope probing (SIP) technique to elucidate a direct pathway for the translocation of (13)C-labeled photoassimilate from maize plants to extraradical mycelium-associated phosphate-solubilizing bacteria (PSB) that mediate the mineralization and turnover of soil organic phosphorus (P) in the hyphosphere. Inoculation with PSB alone did not provide any benefit to maize plants but utilized the added phytate-P to their own advantage, while inoculation with Rhizophagus irregularis alone significantly promoted shoot biomass and P content compared with the control. However, compared with both sole inoculation treatments, combined inoculation with PSB and R. irregularis in the hyphosphere enhanced organic P mineralization and increased microbial biomass P in the soil. There was no extra benefit to plant P uptake but the hyphal growth of R. irregularis was reduced, suggesting that PSB benefited from the arbuscular mycorrhizal (AM) fungal mycelium and competed for soil P with the fungus. The combination of T-RFLP (terminal restriction fragment length polymorphism) analysis with a clone library revealed that one of the bacteria that actively assimilated carbon derived from pulse-labeled maize plants was Pseudomonas alcaligenes (Pseudomonadaceae) that was initially inoculated into the hyphosphere soil. These results provide the first in situ demonstration of the pathway underlying the carbon flux from plants to the AM mycelium-associated PSB, and the PSB assimilated the photosynthates exuded by the fungus and promoted mineralization and turnover of organic P in the soil. PMID- 26802174 TI - Global variations and time trends in the prevalence of childhood myopia, a systematic review and quantitative meta-analysis: implications for aetiology and early prevention. AB - The aim of this review was to quantify the global variation in childhood myopia prevalence over time taking account of demographic and study design factors. A systematic review identified population-based surveys with estimates of childhood myopia prevalence published by February 2015. Multilevel binomial logistic regression of log odds of myopia was used to examine the association with age, gender, urban versus rural setting and survey year, among populations of different ethnic origins, adjusting for study design factors. 143 published articles (42 countries, 374 349 subjects aged 1-18 years, 74 847 myopia cases) were included. Increase in myopia prevalence with age varied by ethnicity. East Asians showed the highest prevalence, reaching 69% (95% credible intervals (CrI) 61% to 77%) at 15 years of age (86% among Singaporean-Chinese). Blacks in Africa had the lowest prevalence; 5.5% at 15 years (95% CrI 3% to 9%). Time trends in myopia prevalence over the last decade were small in whites, increased by 23% in East Asians, with a weaker increase among South Asians. Children from urban environments have 2.6 times the odds of myopia compared with those from rural environments. In whites and East Asians sex differences emerge at about 9 years of age; by late adolescence girls are twice as likely as boys to be myopic. Marked ethnic differences in age-specific prevalence of myopia exist. Rapid increases in myopia prevalence over time, particularly in East Asians, combined with a universally higher risk of myopia in urban settings, suggest that environmental factors play an important role in myopia development, which may offer scope for prevention. PMID- 26802175 TI - Occurrence and risk factors for retinal detachment after pars plana vitrectomy in acute postcataract bacterial endophthalmitis. AB - BACKGROUND/AIMS: To report the incidence, risk factors and prognosis of retinal detachment (RD) in patients who had vitrectomy for acute bacterial endophthalmitis after cataract surgery. METHODS: 123 patients with acute postcataract endophthalmitis, consecutively treated with pars plana vitrectomy (PPV) were included by the French Institutional Endophthalmitis Study group, in a prospective multicentre cohort study. Risk factors of RD were analysed using logistic regression. RESULTS: At the 6-month follow-up, the rate of post-PPV RD was 13% (n=16). The risk factors of post-PPV RD were diabetes (OR=4.7 (1.4-15.4), p=0.01) and visualisation of retinal vasculitis on the posterior pole (OR=3.8 (1.1-13.9), p=0.03) at the time of PPV. Postoperative RD occurred in 56% (n=9) of cases in the first month, in 31% (n=5) in the second month and in 6% (n=1) in the third month, with a mean delay of 47+/-71 days after PPV. The macula was detached in 12 cases (75%) and proliferative vitreoretinopathy grade C was present in seven cases. Final successful reattachment of the retina was obtained in 60% (n=9/15) of cases, with one (7/9) or two surgeries (2/9). Final visual acuity after surgical repair was >=20/40 in 19% of cases, compared with 43% in patients without RD (p=0.05). CONCLUSIONS: RD is a major and severe complication of PPV performed in patients with acute postcataract endophthalmitis. Retinal vasculitis is a major risk factor of RD after PPV. Anatomical and functional outcome remain poor. PMID- 26802177 TI - A Compact Blast-Induced Traumatic Brain Injury Model in Mice. AB - Blast-induced traumatic brain injury (bTBI) is a common injury on the battlefield and often results in permanent cognitive and neurological abnormalities. We report a novel compact device that creates graded bTBI in mice. The injury severity can be controlled by precise pressures that mimic Friedlander shockwave curves. The mouse head was stabilized with a head fixator, and the body was protected with a metal shield; shockwave durations were 3 to 4 milliseconds. Reflective shockwave peak readings at the position of the mouse head were 12 6 2.6 psi, 50 6 20.3 psi, and 100 6 33.1 psi at 100, 200, and 250 psi predetermined driver chamber pressures, respectively. The bTBIs of 250 psi caused 80% mortality, which decreased to 27% with the metal shield. Brain and lung damage depended on the shockwave duration and amplitude. Cognitive deficits were assessed using the Morris water maze, Y-maze, and open-field tests. Pathological changes in the brain included disruption of the blood-brain barrier, multifocal neuronal and axonal degeneration, and reactive gliosis assessed by Evans Blue dye extravasation, silver and Fluoro-Jade B staining, and glial fibrillary acidic protein immunohistochemistry, respectively. Behavioral and pathological changes were injury severity-dependent. This mouse bTBI model may be useful for investigating injury mechanisms and therapeutic strategies associated with bTBI. PMID- 26802178 TI - MicroRNA Expression Patterns in Human Astrocytes in Relation to Anatomical Location and Age. AB - Anatomic distribution and age are variables linked to functions of astrocytes under physiologic and pathologic conditions. We measured the relative expression of a panel of microRNAs (miRNAs) in astrocytes captured by laser micro-dissection from normal human adult white and grey matter, human fetal white matter and germinal matrix samples. Although expression of most miRNAs was comparable between adult and fetal samples, regional differences were observed. In the adult cerebral cortex, expression of miRNAs in morphologically distinct inter-laminar astrocytes underlying the glial limitans differed from those in deeper cortical layers, suggesting functional specialization possibly related to structural stability and defense from potentially harmful factors in the cerebrospinal fluid. Differences between adult white and grey matter miRNA expression included higher expression of pro-inflammatory miRNAs in the former, potentially contributing to differences in inflammation between grey and white matter plaques in multiple sclerosis. Lower expression of miRNAs in fetal versus adult white matter astrocytes likely reflects the immaturity of these migrating cells. Highly expressed miRNAs in the fetal germinal matrix are probably relevant in development and also recapitulate some responses to injury. Future studies can address regional alterations of miRNA expression in pathological conditions. PMID- 26802176 TI - Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma. AB - The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging. We randomly assigned 668 patients between nine 4-week cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/NMSG18 trial). The primary end point was progression-free survival (PFS). A total of 318 patients were randomly assigned to receive MPT-T, and 319 received MPR-R. After a median follow-up of 36 months, PFS with MPT-T was 20 months (95% confidence interval [CI], 18-23 months) vs 23 months (95% CI, 19-27 months) with MPR-R (hazard ratio, 0.87; 95% CI, 0.72-1.04; P = .12). Response rates were similar, with at least a very good partial response of 47% and 45%, respectively. Hematologic toxicity was more pronounced with MPR-R, especially grades 3 and 4 neutropenia: 64% vs 27%. Neuropathy of at least grade 3 was significantly higher in the MPT-T arm: 16% vs 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 vs 17 months in MPR-R), irrespective of age. MPR-R has no advantage over MPT-T concerning efficacy. The toxicity profile differed with clinically significant neuropathy during thalidomide maintenance vs myelosuppression with MPR. PMID- 26802179 TI - Nephrin Tyrosine Phosphorylation Is Required to Stabilize and Restore Podocyte Foot Process Architecture. AB - Podocytes are specialized epithelial cells of the kidney blood filtration barrier that contribute to permselectivity via a series of interdigitating actin-rich foot processes. Positioned between adjacent projections is a unique cell junction known as the slit diaphragm, which is physically connected to the actin cytoskeleton via the transmembrane protein nephrin. Evidence indicates that tyrosine phosphorylation of the intracellular tail of nephrin initiates signaling events, including recruitment of cytoplasmic adaptor proteins Nck1 and Nck2 that regulate actin cytoskeletal dynamics. Nephrin tyrosine phosphorylation is altered in human and experimental renal diseases characterized by pathologic foot process remodeling, prompting the hypothesis that phosphonephrin signaling directly influences podocyte morphology. To explore this possibility, we generated and analyzed knockin mice with mutations that disrupt nephrin tyrosine phosphorylation and Nck1/2 binding (nephrin(Y3F/Y3F) mice). Homozygous nephrin(Y3F/Y3F) mice developed progressive proteinuria accompanied by structural changes in the filtration barrier, including podocyte foot process effacement, irregular thickening of the glomerular basement membrane, and dilated capillary loops, with a similar but later onset phenotype in heterozygous animals. Furthermore, compared with wild-type mice, nephrin(Y3F/Y3F) mice displayed delayed recovery in podocyte injury models. Profiling of nephrin tyrosine phosphorylation dynamics in wild-type mice subjected to podocyte injury indicated site-specific differences in phosphorylation at baseline, injury, and recovery, which correlated with loss of nephrin-Nck1/2 association during foot process effacement. Our results define an essential requirement for nephrin tyrosine phosphorylation in stabilizing podocyte morphology and suggest a model in which dynamic changes in phosphotyrosine-based signaling confer plasticity to the podocyte actin cytoskeleton. PMID- 26802181 TI - Ultrasound findings predict progression to inflammatory arthritis in anti-CCP antibody-positive patients without clinical synovitis. AB - OBJECTIVES: To determine whether ultrasound can identify anti-cyclic citrullinated peptide (anti-CCP) antibody-positive patients without clinical synovitis (CS) who progress to inflammatory arthritis (IA). METHODS: In a prospective study, anti-CCP-positive patients without CS underwent ultrasound imaging of 32 joints (wrists, metacarpophalangeal joints, proximal interphalangeal joints and metatarsophalangeal joints (MTPs)) and were monitored for the development of IA. Associations between baseline ultrasound findings (grey scale (GS), power Doppler (PD) and erosions) and (1) progression to IA and (2) development of CS within an individual joint were measured. RESULTS: Consecutive anti-CCP-positive patients (n=136; mean age 51 years, 100 women) were followed up for median of 18.3 months (range 0.1-79.6). At baseline 96% had GS, 30% had PD and 21% had one or more erosions. IA developed in 57 patients (42%) after median of 8.6 months (range 0.1-52.4). Ultrasound abnormalities (GS >=2, PD >=1 or erosion >=1) were found in 86% at baseline compared with 67% of non progressors (chi2=6.3, p=0.012). Progression to IA was significantly higher in those with ultrasound findings in any joint (excluding MTPs for GS) (GS >=2: 55% vs 24%, HR (95% CI) 2.3 (1.0 to 4.9), p=0.038; PD >=2: 75% vs 32%, 3.7 (2.0 to 6.9), p<0.001 and erosion >=1: 71% vs 34%, 2.9 (1.7 to 5.1), p<0.001). Furthermore, progression occurred earlier with PD >=2 (median 7.1 vs 52.4 months) and erosion >=1 (15.4 vs 46.5). At the individual joint level, the trend for progression to CS was more significant for GS and PD (GS >=2: 26% vs 3%, 9.4 (5.1 to 17.5), p<0.001; PD >=2: 55% vs 4%, 31.3 (15.6 to 62.9), p<0.001). CONCLUSION: Ultrasound features of joint inflammation may be detected in anti-CCP-positive patients without CS. Ultrasound findings predict progression (and rate of progression) to IA, with the risk of progression highest in those with PD signal. TRIAL REGISTRATION NUMBER: NCT02012764; Results. PMID- 26802182 TI - Measurements, composite scores and the art of 'cutting-off'. PMID- 26802180 TI - EULAR recommendations for the management of familial Mediterranean fever. AB - Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease, but many rheumatologists are not well acquainted with its management. The objective of this report is to produce evidence-based recommendations to guide rheumatologists and other health professionals in the treatment and follow up of patients with FMF. A multidisciplinary panel, including rheumatologists, internists, paediatricians, a nurse, a methodologist and a patient representative, was assembled. Panellists came from the Eastern Mediterranean area, Europe and North America. A preliminary systematic literature search on the pharmacological treatment of FMF was performed following which the expert group convened to define aims, scope and users of the guidelines and established the need for additional reviews on controversial topics. In a second meeting, recommendations were discussed and refined in light of available evidence. Finally, agreement with the recommendations was obtained from a larger group of experts through a Delphi survey. The level of evidence (LoE) and grade of recommendation (GR) were then incorporated. The final document comprises 18 recommendations, each presented with its degree of agreement (0-10), LoE, GR and rationale. The degree of agreement was greater than 7/10 in all instances. The more controversial statements were those related to follow-up and dose change, for which supporting evidence is limited. A set of widely accepted recommendations for the treatment and monitoring of FMF is presented, supported by the best available evidence and expert opinion. It is believed that these recommendations will be useful in guiding physicians in the care of patients with FMF. PMID- 26802183 TI - Bagasse hydrolyzates from Agave tequilana as substrates for succinic acid production by Actinobacillus succinogenes in batch and repeated batch reactor. AB - The aim of this work was to obtain fermentable sugars by enzymatic or acid hydrolyses of Agave tequilana Weber bagasse in order to produce succinic acid with Actinobacillus succinogenes. Hydrolyses were carried out with mineral acids (sulfuric and hydrochloric acids) or a commercial cellulolytic enzyme, and were optimized statistically by a response surface methodology, having as factors the concentration of acid/enzyme and time of hydrolysis. The concentration of sugars obtained at optimal conditions for each hydrolysis were 21.7, 22.4y 19.8g/L for H2SO4, HCl and the enzymatic preparation respectively. Concerning succinic acid production, the enzymatic hydrolyzates resulted in the highest yield (0.446g/g) and productivity (0.57g/Lh) using A. succinogenes in a batch reactor system. Repeated batch fermentation with immobilized A. succinogenes in agar and with the enzymatic hydrolyzates resulted in a maximum concentration of succinic acid of 33.6g/L from 87.2g/L monosaccharides after 5 cycles in 40h, obtaining a productivity of 1.32g/Lh. PMID- 26802184 TI - Quantifying pretreatment degradation compounds in solution and accumulated by cells during solids and yeast recycling in the Rapid Bioconversion with Integrated recycling Technology process using AFEXTM corn stover. AB - Effects of degradation products (low molecular weight compounds produced during pretreatment) on the microbes used in the RaBIT (Rapid Bioconversion with Integrated recycling Technology) process that reduces enzyme usage up to 40% by efficient enzyme recycling were studied. Chemical genomic profiling was performed, showing no yeast response differences in hydrolysates produced during RaBIT enzymatic hydrolysis. Concentrations of degradation products in solution were quantified after different enzymatic hydrolysis cycles and fermentation cycles. Intracellular degradation product concentrations were also measured following fermentation. Degradation product concentrations in hydrolysate did not change between RaBIT enzymatic hydrolysis cycles; the cell population retained its ability to oxidize/reduce (detoxify) aldehydes over five RaBIT fermentation cycles; and degradation products accumulated within or on the cells as RaBIT fermentation cycles increased. Synthetic hydrolysate was used to confirm that pretreatment degradation products are the sole cause of decreased xylose consumption during RaBIT fermentations. PMID- 26802185 TI - Thermo-chemical pretreatment and enzymatic hydrolysis for enhancing saccharification of catalpa sawdust. AB - To improve the reducing sugar production from catalpa sawdust, thermo-chemical pretreatments were examined and the chemicals used including NaOH, Ca(OH)2, H2SO4, and HCl. The hemicellulose solubilization and cellulose crystallinity index (CrI) were significantly increased after thermo-alkaline pretreatments, and the thermo-Ca(OH)2 pretreatment showed the best improvement for reducing sugar production comparing to other three pretreatments. The conditions of thermo Ca(OH)2 pretreatment and enzymatic hydrolysis were systematically optimized. Under the optimal conditions, the reducing sugar yield increased by 1185.7% comparing to the control. This study indicates that the thermo-Ca(OH)2 pretreatment is ideal for the saccharification of catalpa sawdust and that catalpa sawdust is a promising raw material for biofuel. PMID- 26802186 TI - Energy requirements for wet solvent extraction of lipids from microalgal biomass. AB - Biofuel production from microalgae requires energy efficient processes for extracting and converting triacylglyceride lipids to fuel, compatible with coproduction of protein feeds and nutraceuticals. Wet solvent extraction involves mechanical cell rupture, lipid extraction via solvent contacting, physical phase separation, thermal solvent recovery, and transesterification. A detailed analysis of the effect of key process parameters on the parasitic energy demand of this process was performed. On a well-to-pump basis, between 16% and 320% of the resultant biodiesel energy was consumed depending solely on the process parameters. Highly positive energy balances can be achieved, but only if a correctly designed process is used. This requires processing concentrated biomass (ca 25%w/w) with a high triacylglyceride content (ca 30%w/w), and an efficient extraction process employing a non-polar solvent, low solvent-to-paste ratio, and efficient energy recovery. These requirements preclude many laboratory scale processes and polar co-solvents as viable options for large-scale biofuel production. PMID- 26802187 TI - A novel approach to calibrate the hemodynamic model using functional Magnetic Resonance Imaging (fMRI) measurements. AB - BACKGROUND: The calibration of the hemodynamic model that describes changes in blood flow and blood oxygenation during brain activation is a crucial step for successfully monitoring and possibly predicting brain activity. This in turn has the potential to provide diagnosis and treatment of brain diseases in early stages. NEW METHOD: We propose an efficient numerical procedure for calibrating the hemodynamic model using some fMRI measurements. The proposed solution methodology is a regularized iterative method equipped with a Kalman filtering type procedure. The Newton component of the proposed method addresses the nonlinear aspect of the problem. The regularization feature is used to ensure the stability of the algorithm. The Kalman filter procedure is incorporated here to address the noise in the data. RESULTS: Numerical results obtained with synthetic data as well as with real fMRI measurements are presented to illustrate the accuracy, robustness to the noise, and the cost-effectiveness of the proposed method. COMPARISON WITH EXISTING METHOD(S): We present numerical results that clearly demonstrate that the proposed method outperforms the Cubature Kalman Filter (CKF), one of the most prominent existing numerical methods. CONCLUSION: We have designed an iterative numerical technique, called the TNM-CKF algorithm, for calibrating the mathematical model that describes the single-event related brain response when fMRI measurements are given. The method appears to be highly accurate and effective in reconstructing the BOLD signal even when the measurements are tainted with high noise level (as high as 30%). PMID- 26802188 TI - Feature clustering for robust frequency-domain classification of EEG activity. AB - BACKGROUND: The analysis of electroencephalograms is often performed in the frequency-domain. These analyses typically involve the computation of spectral power either over pre-defined frequency bands (e.g. theta, delta, alpha, and beta bands) or over a large number of narrow frequency ranges. However, the former technique ignores variability in these frequency bands over time and between participants while the latter ignores the significant redundancy between these powers. NEW METHOD: This paper details an unsupervised feature extraction method for EEG data that uses a clustering of features to agglomerate narrow-band spectral powers based on their similarities. This method computes a set of analogues to the traditional frequency bands that are data-driven and participant specific. A fast correlation-based filter was used to identify which of these agglomerated features were most useful for each investigated classification problem. RESULTS: The new feature clustering algorithm was used to detect changes in three mental states and to detect the performance of three mental tasks. Balanced classification accuracies approaching or exceeding 70% were attained for all classification problems. COMPARISON TO EXISTING METHODS: Classification accuracies attained by this algorithm were compared to those attained by two frequency-domain algorithms that did not employ clustering--a wide-band algorithm based on the spectral power within the theta, delta, alpha, and beta bands and a narrow-band algorithm based on the spectral power within 1-Hz ranges. Overall, the feature clustering algorithm was statistically superior to both alternative algorithms. CONCLUSIONS: The new feature clustering algorithm provides a promising alternative to conventional frequency-domain EEG analysis. PMID- 26802189 TI - Motivational Affordance and Risk-Taking Across Decision Domains. AB - We propose a motivational affordance account to explain both stability and variability in risk-taking propensity in major decision domains. We draw on regulatory focus theory to differentiate two types of motivation (prevention, promotion) that play a key role in predicting risk-taking. Study 1 demonstrated that prevention motivation is negatively associated with risk-taking across six key decision domains, including health/safety, ethics, recreation, gambling, investment, and social. In contrast, promotion motivation is positively associated with risk-taking in the social and investment domains. Study 2 replicated the same pattern and provided direct evidence that promotion motivation is a strong predictor of risk-taking only in domains where there is true potential for gains. Study 3 manipulated promotion (vs. prevention) motivation experimentally to demonstrate that motivational affordance is a critical mechanism for understanding risk-taking behaviors. PMID- 26802190 TI - Severe eosinophilic gastroenteritis. PMID- 26802191 TI - Colonoscopy surveillance after colorectal cancer resection: recommendations of the US multi-society task force on colorectal cancer. PMID- 26802192 TI - Endoscopic palliative treatment using a metallic stent in a patient with an obstructive jejunal metastasis. PMID- 26802193 TI - Melanoma in an unexpected location. PMID- 26802194 TI - Splenic artery pseudoaneurysm causing brisk upper-GI bleed from gastric ulcer. PMID- 26802195 TI - Challenging combined EUS-and-ERCP-endoscopic retrieval of proximally migrated pancreatic stent. PMID- 26802197 TI - Perforation during underwater EMR. PMID- 26802196 TI - Flexible endoscopic treatment for Zenker's diverticulum: a systematic review and meta-analysis. AB - BACKGROUND AND AIMS: Flexible endoscopic septum division (FESD) is a rapidly evolving technique for the treatment of Zenker's diverticulum (ZD). The aim was to perform a systematic review and meta-analysis of the literature focusing on FESD for ZD, including an in-depth evaluation of its efficacy, safety, and limitations. METHODS: A comprehensive literature search was completed to identify papers that examined the efficacy and safety of FESD for ZD. Demographic, clinical, and technical information was retrieved. Main outcomes were extracted, pooled, and analyzed. Heterogeneity among studies was assessed using the I(2) statistic. A random effect model was used as the pooling method in cases of high heterogeneity; otherwise the fixed effect model was applied. Meta-regression was also performed. Main outcomes such as rates of success, adverse events, and recurrences were evaluated. RESULTS: Twenty studies with a total of 813 patients were selected. The pooled success, adverse events, and recurrence rates were 91% (95% confidence interval [CI], 86%-95%; I(2) = 69.5%), 11.3% (95% CI, 8%-16%; I(2) = 64%), and 11% (95% CI, 8%-15%; I(2) = 38.4%), respectively. Substantial heterogeneity across studies was found. However, for success rates, excluding 3 studies reduced heterogeneity to non-significant rates [I(2) = 25.6%; P = .154]. Adverse event rates decreased with larger samples (coefficient, -0.0123; 95% CI, 0.03 to -0.003; P = .017), whereas recurrence rates increased (coefficient, 0.006; 95% CI, -0.0010 to 0.0125; P = .093). Year of publication was negatively associated with success rate, whereas the opposite pattern was found for recurrence rates. CONCLUSIONS: FESD is a feasible, safe, and effective treatment for symptomatic ZD, with low adverse event and recurrence rates. PMID- 26802198 TI - Jejunal volvulus: an exceptional PEG adverse event. PMID- 26802199 TI - Endoscopic treatment of a refractory intrahepatic bile leak by transpapillary placement of coils into a peripheral bile duct. PMID- 26802200 TI - Salvage ERCP using overtube-assisted technique in a patient with cholangitis and esophageal stenosis due to achalasia. PMID- 26802201 TI - EUS-directed jejunogastric lumen-apposing metal stent to facilitate cystgastrostomy in a patient with Roux-en-Y anatomy. PMID- 26802202 TI - Endoscopic sphincterotomy using an isolated-tip needle-knife papillotome after Billroth II gastrectomy. PMID- 26802203 TI - EUS-guided pancreatic drainage for recurrent pancreatitis. PMID- 26802204 TI - The dual edge of RNA silencing suppressors in the virus-host interactions. AB - RNA silencing (or RNA interference, RNAi) plays a key role in the plant antiviral defense. To facilitate infection, viruses encode suppressors of RNA silencing (VSRs) to counteract antiviral defense. In the co-evolutionary arms race between hosts and viruses, extreme viral accumulation does not benefit either hosts or viruses. During viral infection, antiviral silencing and VSRs have dual effects to maintain the balance between plant development and virus accumulation. Here, we summarize and discuss the multiple functions of the antiviral RNAi defense and VSRs, revealing the central hub regulators of VSRs in dynamically integrated connections between hosts and viruses. PMID- 26802205 TI - Predictors of outcomes in children awaiting heart transplantation: an experience from a National Paediatric Heart Transplantation Programme. AB - OBJECTIVES: The risk of mortality while awaiting heart transplantation (HT) may be greater in the setting of a smaller population and lower donor organ rates. Optimizing allocation policy and identifying the most vulnerable patients will help reduce mortality. As such, we aimed to evaluate the predictors of outcomes in patients awaiting HT as part of a National Paediatric HT Programme. METHODS: Between 1988 and 2015, 200 children were listed for HT as part of a National Paediatric HT Programme. We categorized patients as experiencing one of four competing events: (i) transplant, (ii) death, (iii) delisting for clinical deterioration and (iv) delisting for clinical improvement. Comparison was made across three study eras: Era 1: 1988-95; Era 2: 1996-2005; Era 3: 2006-15. A multivariable competing risk regression analysis was performed to determine the independent predictors of transplantation and the composite event of death or delisting for clinical deterioration. RESULTS: Among the 200 patients listed, 60% (119/200) underwent transplantation, 22% (44/200) died on the waiting list, 7% (13/200) were delisted for clinical deterioration and 11% (21/200) were delisted due to clinical improvement, with 2% (3/200) being still active on the waiting list. The mortality-rate for patients who remained on the waiting list decreased from 27% in Era 1 to 18% in Era 3. The survival from wait-listing was 57, 47 and 39% at 5, 10 and 15 years, respectively. On multivariable competing risk regression, older age (HR 1.09, 95% CI 1.01-1.18, P = 0.029) and the absence of inotropic support (HR 2.22, 1.23-4.00, P = 0.0073) were predictors of reaching transplantation. Higher creatinine (per 20 umol/l, HR 1.42, 1.03-1.95, P = 0.03) was a predictor of the composite endpoint of death or delisting for deterioration. CONCLUSIONS: In this analysis of a National Paediatric HT Programme, waiting-list mortality has decreased over time though it remains higher than countries with higher donor rates. The requirement for inotropic support and worsening renal function were predictors of failure to reach transplantation. These patients are likely to benefit the most from ventricular assist device therapy and higher priority listing. PMID- 26802206 TI - Genetic evaluation of ex situ conservation breeding projects of Cheer Pheasant (Catreus wallichii) and Western Tragopan (Tragopan melanocephalus) in India. AB - When setting-up a captive population, genetic assessment of founders is essential to formulate effective breeding strategies that minimize the negative effects of inbreeding in the successive generations caused by mating between genetically related individuals. We carried out molecular genetic analysis of Cheer Pheasant and Western Tragopan populations of Chail and Sarahan Pheasantries in the State of Himachal Pradesh. The results revealed that the captive stock of Cheer Pheasant is sustaining well and does not exhibit signatures of inbreeding. Conversely, inbreeding is strongly evident in Western Tragopan population. Our study adds new dimensions to the captive management of Cheer Pheasant and Western Tragopan populations and contradicts with a previous study conducted on the same Western Tragopan population of Sarahan Pheasantry using studbook data. This study demonstrates strong evidence for retaining genetic assessment as an integral part to formulate policies/strategies for conservation breeding projects and proposes refining existing studbook records by incorporating microsatellites data and genetic analyses. Zoo Biol. 35:269-273, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26802207 TI - The Green Clade grows: A phylogenetic analysis of Aplastodiscus (Anura; Hylidae). AB - Green tree frogs of the genus Aplastodiscus occur in the Atlantic Forest and Cerrado biomes of South America. The genus comprises 15 medium-sized species placed in three species groups diagnosed mainly by cloacal morphology. A phylogenetic analysis was conducted to: (1) test the monophyly of these species groups; (2) explore the phylogenetic relationships among putative species; and (3) investigate species boundaries. The dataset included eight mitochondrial and nuclear gene fragments for up to 6642 bp per specimen. The results strongly support the monophyly of Aplastodiscus and of the A. albofrenatus and A. perviridis groups. Aplastodiscus sibilatus is the sister taxon of all other species of Aplastodiscus, making the A. albosignatus Group non-monophyletic as currently defined. At least six unnamed species are recognized for Aplastodiscus, increasing the diversity of the genus by 40%. A fourth species group, the A. sibilatus Group is recognized. Aplastodiscus musicus is transferred from the A. albofrenatus Group to the A. albosignatus Group, and A. callipygius is considered a junior synonym of A. albosignatus. Characters related to external cloacal morphology reveal an interesting evolutionary pattern of parallelisms and reversions, suggesting an undocumented level of complexity. We analyze, in light of our phylogenetic results, the evolution of reproductive biology and chromosome morphology in Aplastodiscus. PMID- 26802208 TI - Diversity-dependent cladogenesis throughout western Mexico: Evolutionary biogeography of rattlesnakes (Viperidae: Crotalinae: Crotalus and Sistrurus). AB - Rattlesnakes (Crotalus and Sistrurus) represent a radiation of approximately 42 species distributed throughout the New World from southern Canada to Argentina. Interest in this enigmatic group of snakes continues to accrue due, in part, to their ecomorphological diversity, contributions to global envenomations, and potential medicinal importance. Although the group has garnered substantial attention from systematists and evolutionary biologists for decades, little is still known regarding patterns of lineage diversification. In addition, few studies have statistically quantified broad-scale biogeographic patterns in rattlesnakes to ascertain how dispersal occurred throughout the New World, particularly among the different major biomes of the Americas. To examine diversification and biogeographic patterns in this group of snakes we assemble a multilocus data set consisting of over 6700bp encompassing three nuclear loci (NT 3, RAG-1, C-mos) and seven mitochondrial genes (12S, 16S, ATPase6, ATPase8, ND4, ND5, cytb). Fossil-calibrated phylogenetic and subsequent diversification rate analyses are implemented using maximum likelihood and Bayesian inference, to examine their evolutionary history and temporal dynamics of diversity. Based on ancestral area reconstructions we explore dispersal patterns throughout the New World. Cladogenesis occurred predominantly during the Miocene and Pliocene with only two divergences during the Pleistocene. Two different diversification rate models, advocating diversity-dependence, are strongly supported. These models indicate an early rapid radiation followed by a recent speciation rate decline. Biogeographic analyses suggest that the high elevation pine-oak forests of western Mexico served as a major speciation pump for the majority of lineages, with the desert biome of western North America colonized independently at least twice. All together, these results provide evidence for rapid diversification of rattlesnakes throughout the Mexican highlands during the Neogene, likely in response to continual orogenesis of Mexico's major mountain systems, followed by more recent dispersal into desert and tropical biomes. PMID- 26802209 TI - HAPCAD: An open-source tool to detect PCR crossovers in next-generation sequencing generated HLA data. AB - Next-generation sequencing (NGS) based HLA genotyping can generate PCR artifacts corresponding to IMGT/HLA Database alleles, for which multiple examples have been observed, including sequence corresponding to the HLA-DRB1(*)03:42 allele. Repeat genotyping of 131 samples, previously genotyped as DRB1(*)03:01 homozygotes using probe-based methods, resulted in the heterozygous call DRB1(*)03:01+DRB1(*)03:42. The apparent rare DRB1(*)03:42 allele is hypothesized to be a "hybrid amplicon" generated by PCR crossover, a process in which a partial PCR product denatures from its template, anneals to a different allele template, and extends to completion. Unlike most PCR crossover products, "hybrid amplicons" always corresponds to an IMGT/HLA Database allele, necessitating a case-by-case analysis of whether its occurrence reflects the actual allele or is simply the result of PCR crossover. The Hybrid Amplicon/PCR Crossover Artifact Detector (HAPCAD) program mimics jumping PCR in silico and flags allele sequences that may also be generated as hybrid amplicon. PMID- 26802210 TI - Cytoplasmic tail domain of glycoprotein B is essential for HHV-6 infection. AB - Human herpesvirus 6 (HHV-6) glycoprotein B (gB) is an abundantly expressed viral glycoprotein required for viral entry and cell fusion, and is highly conserved among herpesviruses. The present study examined the function of HHV-6 gB cytoplasmic tail domain (CTD). A gB CTD deletion mutant was constructed which, in contrast to its revertant, could not be reconstituted. Moreover, deletion of gB cytoplasmic tail impaired the intracellular transport of gB protein to the trans Golgi network (TGN). Taken together, these results suggest that gB CTD is critical for HHV-6 propagation and important for intracellular transportation. PMID- 26802211 TI - Repeat lumbar puncture in adults with bacterial meningitis. AB - In a prospective nationwide cohort study performed in the Netherlands from 2006 to 2014 we analysed clinical and laboratory characteristics of adults with community-acquired bacterial meningitis who underwent repeat lumbar puncture. Repeat lumbar puncture was performed in 124 of 1490 included episodes (8%), most commonly because of clinical deterioration (42%). Median cerebrospinal fluid (CSF) leucocyte count on admission was 1473 cells/mm(3). Median CSF cell count showed a decrease of 19% when repeated within 2 days; of 84% within 3-7 days, of 93% within 8-14 days and of 98% within 15-21 days. Repeat lumbar puncture confirmed the diagnosis of meningitis in eight patients with normal initial CSF examination. Repeat CSF cultures yielded bacteria in nine patients, which led to identification of an underlying source of infection in two. We conclude that repeat lumbar puncture is performed in a small proportion of adults. Although it should not be seen as routine it can be useful in selected cases to confirm diagnosis, to exclude relapsing or persistent infection, or for therapeutic purpose in communicating hydrocephalus. PMID- 26802212 TI - Serum microRNA-125b correlates with hepatitis B viral replication and liver necroinflammation. AB - MicroRNAs (miRNAs) were recently reported to play an important role in hepatitis B virus (HBV) infection and related diseases. We evaluated the correlation between serum miRNA-125b, viral replication and liver necroinflammation in Chinese patients with chronic hepatitis B (CHB) infection. Serum miRNA-125b levels in samples from 211 CHB patients were determined by RT-PCR. Liver biopsies were collected from 138 patients. Serum miRNA-125b, miRNA-122 and miRNA-124 levels were determined. Correlations between serum miRNA-125b, viral replication and liver necroinflammation were analysed. The receiver operating characteristic (ROC) curve was used to assess the discriminating power of serum miRNA-125b to grade liver necroinflammation (G). HepG2.2.15 cells were transfected with miRNA 125b mimics. Intracellular viral core DNA was extracted and analysed by Southern blot. We found that serum miRNA-125b was positively correlated with the serum HBV DNA level. HBV replication capacity increased after transfection with miRNA-125b mimics. Patients with CHB with moderate-to-severe liver necroinflammation (G >=2) showed significantly higher (p <0.001) serum miRNA-125b levels than those with G <2. In patients with alanine transaminase levels less than twice the upper limit of normal, serum miRNA-125b combined with miRNA-124 yielded an area under the ROC curve of 0.816, with 70.4% sensitivity and 84.9% specificity to discriminate the grade of liver necroinflammation (G >=2). Hence, we concluded that miRNA-125b may enhance HBV replication. Serum miRNA-125b correlates with viral load. Serum miRNA 125b alone or combined with miRNA-124 has the potential to discriminate grades of liver necroinflammation, particularly in Chinese patients with CHB who have normal or mildly increased alanine transaminase levels. PMID- 26802213 TI - Aspergillus spp. invasive external otitis: favourable outcome with a medical approach. AB - Aspergillus spp. invasive external otitis (IEO) is a rare infection. We performed a seven-year, single-centre retrospective study from 2007 to 2014 including all patients with proven Aspergillus spp. IEO. Twelve patients were identified. All patients had a poorly controlled diabetes mellitus and one underwent solid organ transplant. The most frequently isolated species was Aspergillus flavus (n = 10) and voriconazole was the first-line therapy in all cases, with a median length of treatment of 338.5 days (158-804 days). None of the patients underwent extensive surgery. The clinical outcome was excellent. However, otological sequelae were reported, including hearing impairment (n = 7) and facial palsy (n = 3). PMID- 26802214 TI - Metagenomic analysis of viral genetic diversity in respiratory samples from children with severe acute respiratory infection in China. AB - Severe acute respiratory infection (SARI) in children is thought to be mainly caused by infection with various viruses, some of which have been well characterized; however, analyses of respiratory tract viromes among children with SARI versus those without are limited. In this study, nasopharyngeal swabs from children with and without SARI (135 versus 15) were collected in China between 2008 and 2010 and subjected to multiplex metagenomic analyses using a next generation sequencing platform. The results show that members of the Paramyxoviridae, Coronaviridae, Parvoviridae, Orthomyxoviridae, Picornaviridae, Anelloviridae and Adenoviridae families represented the most abundant species identified (>50% genome coverage) in the respiratory tracts of children with SARI. The viral population found in the respiratory tracts of children without SARI was less diverse and mainly dominated by the Anelloviridae family with only a small proportion of common epidemic respiratory viruses. Several almost complete viral genomes were assembled, and the genetic diversity was determined among several samples based on next-generation sequencing. This research provides comprehensive mapping of the viromes of children with SARI and indicates high heterogeneity of known viruses present in the childhood respiratory tract, which may benefit the detection and prevention of respiratory disease. PMID- 26802215 TI - Interest of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography for the diagnosis of relapse in patients with spinal infection: a prospective study. AB - Relapse after treatment of a spinal infection is infrequent and difficult to diagnose. The aim of this study was to assess the diagnostic performance of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in this setting. Thirty patients (21 men, nine women; median age 61.2 years) with a suspected spinal infection relapse were prospectively included between March 2010 and June 2013. The initial diagnosis of spinal infection was confirmed by positive bacterial cultures. The patients underwent [(18)F]FDG PET/CT and magnetic resonance imaging (MRI) 1 month after antibiotic treatment interruption. PET/CT data were interpreted both visually and semi-quantitatively (SUVmax). The patients were followed for >=12 months and the final diagnosis of relapse was based on new microbiological cultures. Seven patients relapsed during follow up. Sensitivity, specificity, positive predictive value and negative predictive value were 66.6%, 61.9%, 33.3% and 86.6%, respectively for MRI and 85.7, 82.6, 60.0 and 95.0 for PET/CT. Although these values were higher for PET/CT than for MRI, the difference was not statistically significant (p=0.3). [(18)F]FDG PET/CT may be useful for diagnosing a relapse of spinal infections, in particular if metallic implants limit the performance of MRI. PMID- 26802216 TI - Clinical and laboratory features of human herpesvirus 6 chromosomal integration. AB - Human herpesvirus 6 (HHV-6) comprises two separate viruses, HHV-6A and HHV-6B, although this distinction is not commonly made. HHV-6B is ubiquitous in the population with primary infection usually occurring in early childhood, and often resulting in febrile illness. HHV-6B is also recognized as a pathogen in the immunocompromised host, particularly in transplant recipients. HHV-6A is less well characterized and may have a more restricted prevalence. Both viruses are unique among the human herpesviruses in that the entire viral genome can be found integrated into the telomeric regions of host cell chromosomes. Approximately 1% of persons have inherited integrated viral sequences through the germline, and these individuals characteristically have very high viral loads in blood and other sample types. Emerging evidence suggests that HHV-6A and HHV-6B chromosomal integration may not just be an uncommon biological observation, but more likely a characteristic of the replication properties of these viruses. The integrated viral genome appears capable of excision from the chromosomal site and potentially allows viral replication. The clinical consequences of inherited chromosomally integrated HHV-6 have yet to be fully appreciated. PMID- 26802219 TI - Gd(III) complexes as paramagnetic tags: Evaluation of the spin delocalization over the nuclei of the ligand. AB - Complexes of the Gd(III) ion are currently being established as spin labels for distance determination in biomolecules by pulse dipolar spectroscopy. Because Gd(III) is an f ion, one expects electron spin density to be localized on the Gd(III) ion - an important feature for the mentioned application. Most of the complex ligands have nitrogens as Gd(III) coordinating atoms. Therefore, measurement of the (14)N hyperfine coupling gives access to information on the localization of the electron spin on the Gd(III) ion. We carried out W-band, 1D and 2D (14)N and (1)H ENDOR measurements on the Gd(III) complexes Gd-DOTA, Gd 538, Gd-595, and Gd-PyMTA that serve as spin labels for Gd-Gd distance measurements. The obtained (14)N spectra are particularly well resolved, revealing both the hyperfine and nuclear quadrupole splittings, which were assigned using 2D Mims ENDOR experiments. Additionally, the spectral contributions of the two different types of nitrogen atoms of Gd-PyMTA, the aliphatic N atom and the pyridine N atom, were distinguishable. The (14)N hyperfine interaction was found to have a very small isotropic hyperfine component of -0.25 to -0.37MHz. Furthermore, the anisotropic hyperfine interactions with the (14)N nuclei and with the non-exchangeable protons of the ligands are well described by the point-dipole approximation using distances derived from the crystal structures. We therefore conclude that the spin density is fully localized on the Gd(III) ion and that the spin density distribution over the nuclei of the ligands is rightfully ignored when analyzing distance measurements. PMID- 26802217 TI - The Diversity and Molecular Evolution of B-Cell Receptors during Infection. AB - B-cell receptors (BCRs) are membrane-bound immunoglobulins that recognize and bind foreign proteins (antigens). BCRs are formed through random somatic changes of germline DNA, creating a vast repertoire of unique sequences that enable individuals to recognize a diverse range of antigens. After encountering antigen for the first time, BCRs undergo a process of affinity maturation, whereby cycles of rapid somatic mutation and selection lead to improved antigen binding. This constitutes an accelerated evolutionary process that takes place over days or weeks. Next-generation sequencing of the gene regions that determine BCR binding has begun to reveal the diversity and dynamics of BCR repertoires in unprecedented detail. Although this new type of sequence data has the potential to revolutionize our understanding of infection dynamics, quantitative analysis is complicated by the unique biology and high diversity of BCR sequences. Models and concepts from molecular evolution and phylogenetics that have been applied successfully to rapidly evolving pathogen populations are increasingly being adopted to study BCR diversity and divergence within individuals. However, BCR dynamics may violate key assumptions of many standard evolutionary methods, as they do not descend from a single ancestor, and experience biased mutation. Here, we review the application of evolutionary models to BCR repertoires and discuss the issues we believe need be addressed for this interdisciplinary field to flourish. PMID- 26802220 TI - Insulin resistance: The linchpin between prediabetes and cardiovascular disease. AB - The aim of this study was to test the hypothesis that cardiovascular disease occurs to the greatest extent in persons with prediabetes mellitus who are also insulin resistant. In 2003, 664 non-diabetic women (n = 457) and men (n = 207), aged 52 +/- 16 and 53 +/- 15 years, were surveyed during a programme for cardiovascular disease prevention. Fasting plasma glucose concentrations defined participants as having normal fasting plasma glucose (fasting plasma glucose <5.6 mmol/L) or prediabetes mellitus (fasting plasma glucose ? 5.6 and <7.0 mmol/L). The tertile of prediabetes mellitus subjects with the highest fasting plasma insulin concentration was classified as insulin resistant. Baseline cardiovascular disease risk factors were accentuated in prediabetes mellitus versus normal fasting glucose, particularly in prediabetes mellitus/insulin resistant. In 2012, 86% of the sample were surveyed again, and the crude incidence for cardiovascular disease was higher in subjects with prediabetes mellitus versus normal fasting glucose (13.7 vs 6.0/100 persons/10 years; age- and sex-adjusted hazard ratio = 1.88, p = 0.052). In prediabetes mellitus, the crude incidences were 22.9 versus 9.6/100 persons/10 years in insulin resistant versus non-insulin resistant persons (age- and sex-adjusted hazard ratio = 2.36, p = 0.040). In conclusion, cardiovascular disease risk was accentuated in prediabetes mellitus/insulin resistant individuals, with a relative risk approximately twice as high compared to prediabetes mellitus/non-insulin resistant subjects. PMID- 26802218 TI - Purifying Selection on Exonic Splice Enhancers in Intronless Genes. AB - Exonic splice enhancers (ESEs) are short nucleotide motifs, enriched near exon ends, that enhance the recognition of the splice site and thus promote splicing. Are intronless genes under selection to avoid these motifs so as not to attract the splicing machinery to an mRNA that should not be spliced, thereby preventing the production of an aberrant transcript? Consistent with this possibility, we find that ESEs in putative recent retrocopies are at a higher density and evolving faster than those in other intronless genes, suggesting that they are being lost. Moreover, intronless genes are less dense in putative ESEs than intron-containing ones. However, this latter difference is likely due to the skewed base composition of intronless sequences, a skew that is in line with the general GC richness of few exon genes. Indeed, after controlling for such biases, we find that both intronless and intron-containing genes are denser in ESEs than expected by chance. Importantly, nucleotide-controlled analysis of evolutionary rates at synonymous sites in ESEs indicates that the ESEs in intronless genes are under purifying selection in both human and mouse. We conclude that on the loss of introns, some but not all, ESE motifs are lost, the remainder having functions beyond a role in splice promotion. These results have implications for the design of intronless transgenes and for understanding the causes of selection on synonymous sites. PMID- 26802221 TI - Low-density lipoprotein cholesterol level and statin use among Medicare beneficiaries with diabetes mellitus. AB - At the time of this study, guidelines recommended a primary goal of low-density lipoprotein cholesterol level less than 100 mg/dL for all patients, an optional goal of low-density lipoprotein cholesterol less than 70 mg/dL for patients with overt cardiovascular disease and statins for patients with diabetes and overt cardiovascular disease and patients 40 years and older with diabetes and at least one risk factor for cardiovascular disease. This study examined statin use and achievement of lipid goals among 111,730 Medicare fee-for-service beneficiaries 65 years and older in 2011. Three-quarters of patients met the low-density lipoprotein cholesterol goal of less than 100 mg/dL. Patients with cardiovascular disease were more likely to meet the goal than those without, not controlling for other differences. Patients on a statin were more likely to meet the goal. There is considerable opportunity for improvement in cholesterol management in high risk patients with diabetes mellitus. PMID- 26802222 TI - Reasons and outcomes of conversion of laparoscopic sleeve gastrectomy to Roux-en Y gastric bypass for nonresponders. AB - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) as a primary bariatric procedure has gained significant popularity. Conversion to Roux-en-Y gastric bypass (RYGBP) or Roux-en-Y esophagojejunostomy (LRYEJ) has been described as a treatment option for inadequate weight loss after LSG and unresolved co morbidities or complications such as leak, stricture, and severe gastroesophageal reflux disease (GERD). OBJECTIVES: To determine reasons and outcomes of conversions of LSG to RYGBP. SETTING: Academic Center of Excellence METHODS: Between January 2004 and August 2014, a total of 1118 patients underwent primary LSG for morbid obesity. A retrospective review of a prospectively collected database was conducted for laparoscopic conversions of LSG to RYGBP or LRYEJ, describing reasons and outcomes. RESULTS: Conversion to RYGBP was identified in 30 (2.7%) patients, of whom only 9 (0.8%) were originally from the authors' institution. Of the entire cohort of revisions, 9 (0.8%) had intractable GERD; only 4 (0.4% of total LSGs reviewed) were originally from the authors' institution. Seven (0.6%) patients were revised for inadequate weight loss: 5 (0.4%) originally from the authors' institution, 2 (0.2%) for stricture, and 12 (1.1%) for leak. Both the stricture and the leak patients were referred from outside institutions. All procedures were performed laparoscopically. The additional mean excess weight loss after conversion to RYGBP was 30.9% with no mortalities. CONCLUSIONS: The most common reason for conversion was chronic leak. The conversion rate of LSG to RYGBP due to inadequate weight loss, GERD, and stricture was 1.6% for the entire group, with .8% from the authors' institution. Additional follow-up and studies are needed to define real incidence of GERD after LSG. PMID- 26802223 TI - Reducing complications with improving gastric band design. AB - BACKGROUND: Adjustable gastric bands have undergone significant design changes since their introduction. Band diameter, balloon volume, and shape have been modified to create high balloon fill volumes but lower and more evenly distributed pressure on the upper stomach. There have been few comparative studies on complication rates with different band types. OBJECTIVES: To compare complication rates among different types of adjustable gastric bands at a single institution. SETTING: University-affiliated hospital, United States. METHODS: We performed a retrospective cohort study of adult patients with a body mass index >= 35.0 kg/m(2) who underwent laparoscopic adjustable gastric banding from January 1, 2001 to December 31, 2007 and were followed for at least 5 years. Primary outcomes of the analysis were complications requiring operative management at our institution within the first 5 years after initial band placement. Reoperative procedures included diagnostic laparoscopy, hiatal hernia repair, band repositioning, replacing the band, removing the band, and converting to another bariatric procedure. RESULTS: For this study, 2711 patients met the inclusion criteria-1827 (67.4%) women and 884 (32.6%) men. Bands initially implanted included first-generation bands, LAP-BANDTM 9.75 cm (24.0%), 10 cm (33.9%) and Vanguard (24.8%) and second-generation bands, AP standard (9.5%) and AP large (7.9%). Four hundred and eighty-five patients experienced complications requiring reoperation. The 5-year follow-up rate was 63.3%. In the first 5 postoperative years there were significantly fewer complications with second generation bands (10.0% versus 19.5%, P<.0001). Smaller, older bands had the highest complication rates (LAP-BAND 9.75 cm, 28.2%) and complication rates decreased with each successive model. Rates of band removal were not different between first- and second-generation bands. The rate of multiple complications was low at 1.5%. CONCLUSION: First-generation bands are associated with higher complication rates. Our study found that complication rates decreased with each successive model. We can expect that future design modifications will continue improve the performance with the adjustable gastric band. PMID- 26802224 TI - Comment on: Postoperative marijuana use and disordered eating among bariatric surgery patients. PMID- 26802225 TI - Retention and attrition in bariatric surgery research: an integrative review of the literature. AB - BACKGROUND: Bariatric surgery research, often longitudinal, bears the challenge of maintaining retention and decreasing attrition of participants to avoid bias. OBJECTIVES: To explore factors influencing the retention and attrition for bariatric surgical research participants. METHODS: Databases searched included: PubMed, CINAHL, Scopus, and others. As a secondary aim, studies reporting on retention/attrition factors in clinical follow-up visits were included. RESULTS: Of the 1145 articles retrieved, 44 met inclusion criteria, and underwent qualitative analysis. Four descriptive articles focused on longitudinal research participation and 40 on clinical follow-up visits. Willingness to participate in research was high (92%) and decreased with more invasive procedures or extra visits. A large observational longitudinal study presented 24-month retention/attrition data (92% for some data and 66% visit completion) and the retention strategies employed. One study indicated that research follow-up possibly increased clinical follow-up and another demonstrated a higher retention by increasing compensation. No consistent, modifiable demographic or psychosocial variables associated or predictive of retention or attrition in clinical follow up were identified. CONCLUSIONS: Research on factors related to participant retention and attrition is sparse. It is essential for studies to document retention/attrition data. Existing research has demonstrated a patient willingness to participate in research and that retention strategies have been successful in the short term. Further research should explore the motivations, perspectives and attitudes of bariatric surgical research participants regarding participation and explore predictors to develop evidence-based retention strategies. Research has yet to identify consistent and modifiable demographic or psychosocial variables predictive of clinical follow-up, possibly due to the heterogeneity of follow-up across studies. Further investigation into follow-up definition, content, counseling approaches, and new telemedicine technologies may prove helpful in developing predictors and evidence-based strategies. The relationship between research and clinical retention and attrition deserves further characterization. PMID- 26802226 TI - Laparoscopic sleeve gastrectomy in children and adolescents with Prader-Willi Syndrome: a matched control study. PMID- 26802227 TI - Response to the Letter to the Editor: "Comment on the REDUCE trial article: is it really as good as it sounds?". PMID- 26802228 TI - SOARD Category 1 CME Credit Featured Articles, Volume 12, January 2016. PMID- 26802229 TI - Dermatology's Researchers of the Future: Our Workforce Pipeline and Richest Opportunities. PMID- 26802231 TI - The Growing Spectrum of Cutaneous RASopathy. AB - Groesser et al. demonstrate that pyogenic granuloma is a RAS pathway-driven tumor. This important observation adds yet another manifestation to the growing spectrum of cutaneous "RASopathies" and raises intriguing questions about the relationship between RAS pathway activation and malignancy. PMID- 26802230 TI - Progress toward Treatment and Cure of Epidermolysis Bullosa: Summary of the DEBRA International Research Symposium EB2015. AB - Epidermolysis bullosa (EB), a group of complex heritable blistering diseases, is the topic of triennial research meetings organized by DEBRA International, Vienna, Austria, the network of national EB patient advocacy organizations. The DEBRA 2015 Research Conference, held in May 2015, brought together investigators and clinicians from around the world working at the forefront of EB research. Discussing the state-of-the-art approaches from a wide range of disciplines, there was a palpable excitement at this conference brought about by the optimism about applying new sequencing techniques, genome editing, protein replacement, autologous and allogeneic stem cell therapy, innovations in cancer biology, revertant mosaicism, and induced pluripotent stem cell techniques, all of which are aimed at developing new therapies for EB. Many in the field who have participated in EB research for many years were especially enthusiastic and felt that, possibly for the first time, the field seems uniquely poised to bring these new tools to effectively tackle EB. Multiple complementary approaches are currently in motion toward improved quality of life and eventually a cure for patients suffering from EB, a currently intractable disease. PMID- 26802232 TI - Another Piece in the Fibrotic Puzzle: TSLP as a Novel Ligand for Fibrocyte Activation. AB - Thymic stromal lymphopoietin (TSLP) has emerged as an important cytokine in the pathogenesis of nonallergic diseases, especially in diseases that include fibrosis. It has been shown to be upregulated in both cutaneous and lung fibrotic conditions. Shin et al. report that TSLP may also play a role in the pathogenesis of keloids. The main mechanism of TSLP profibrotic effects is not as yet fully understood, although the data suggest that it involves collagen production through transforming growth factor-beta, at least in the case of dermal fibroblasts. The authors also report that TSLP is able to activate fibrocytes, probably by inducing stromal cell-derived factor-1 (also termed CXCL12), one of its main ligands. These findings support the concept that TSLP plays a role in the development of fibrosis, and they should lead to mechanistic studies on TSLP profibrotic signaling. PMID- 26802233 TI - Guiding the Killer and Bringing in Accomplices: Bispecific Antibody Treatment for Malignant Melanoma. AB - Discovery of oncogene and immune checkpoint targeting has transformed melanoma therapy in the last 5 years. However, treatment of primary or secondary drug resistant melanoma remains a challenge. Agents designed to activate the cell death machinery directly, for example by activating the death receptors expressed by melanoma cells, could break drug resistance, and they may achieve long-lasting therapeutic success. He et al. report their studies of an MCSPxDR5 bispecific, tetravalent antibody that can simultaneously target death receptor 5 (DR5, TRAIL R2) and melanoma-associated chondroitin sulfate proteoglycan (MCSP). This antibody can exert strong and selective DR5-dependent cytotoxic activity against MCSP-expressing melanoma cells. Crosslinking of the antibody with Fcgamma receptors increased the cytotoxic potential further, without compromising its selectivity. This approach offers a novel immunotherapeutic tool via coupling of three cooperating processes: delivering the death receptor agonist to the malignant cell population, potent activation of DR5-mediated cell death signaling, and recruitment of Fcgamma-receptor-carrying immune cells that can mount an immune response against the tumor cells. PMID- 26802234 TI - microRNAs in Psoriasis. AB - Psoriasis is a chronic inflammatory skin condition resulting from a complex interplay among the immune system, keratinocytes, susceptibility genes, and environmental factors. However, the pathogenesis of psoriasis is not completely elucidated. microRNAs represent a promising class of small, noncoding RNA molecules that function to regulate gene expression. Although microRNA research in psoriasis and dermatology is still relatively new, evidence is rapidly accumulating for the role of microRNAs in the pathogenesis of psoriasis and other chronic inflammatory conditions. In this article, we present a comprehensive review of what is known about microRNAs and their role in the pathogenesis of psoriasis. PMID- 26802235 TI - The Role of Neutrophilic Inflammation, Angiotropism, and Pericytic Mimicry in Melanoma Progression and Metastasis. AB - Angiotropism in melanoma correlates with ulceration and poor prognosis. It has been shown to be a marker of pericytic mimicry, that is, the spreading of tumor cells in a pericyte location along abluminal vascular surfaces. Such extravascular tumor spread may represent another form of tumor plasticity with reversion to a neural crest cell migratory phenotype. In a murine melanoma model, it has recently been demonstrated that neutrophilic skin inflammation promotes angiotropism and metastatic spread of primary melanomas. This review discusses the role of neutrophilic inflammation in angiotropism and pericytic mimicry in melanoma progression, metastasis, tumor cell plasticity, and tumor therapeutic resistance. PMID- 26802236 TI - Epiplakin Is a Paraneoplastic Pemphigus Autoantigen and Related to Bronchiolitis Obliterans in Japanese Patients. AB - All plakin family proteins are known to be autoantigens in paraneoplastic pemphigus (PNP). In this study, we first examined whether PNP sera also react with epiplakin, another plakin protein, by various immunological methods using 48 Japanese PNP sera. Immunofluorescence confirmed that cultured keratinocytes expressed epiplakin. Epiplakin was detected by 72.9% of PNP sera by immunoprecipitation-immunoblotting with KU-8 cell extract, but not by immunoblotting of either normal human epidermal extract or KU-8 cell extract. Epiplakin was essentially not detected by 95 disease and normal control sera. Statistical analyses of various clinical and immunological findings revealed a significant correlation of the presence of anti-epiplakin antibodies with both bronchiolitis obliterans and mortality. No epiplakin-negative PNP case developed bronchiolitis obliterans. However, although 29.4% of European patients with PNP had bronchiolitis obliterans, significant correlation with anti-epiplakin autoantibodies was not observed. In further studies for lung, immunofluorescence showed the presence of epiplakin in normal human lung, particularly respiratory bronchiole, immunoprecipitation-immunoblotting showed that PNP sera reacted with epiplakin in cultured lung cells, and mice injected with polyclonal antibody specific to epiplakin histopathologically showed abnormal changes in small airway epithelia. These results indicated that epiplakin is one of the major PNP autoantigens and is related to PNP-related bronchiolitis obliterans. PMID- 26802238 TI - Neutrophils Self-Regulate Immune Complex-Mediated Cutaneous Inflammation through CXCL2. AB - Deposition of immune complexes (ICs) in tissues triggers acute inflammatory pathology characterized by massive neutrophil influx leading to edema and hemorrhage, and is especially associated with vasculitis of the skin, but the mechanisms that regulate this type III hypersensitivity process remain poorly understood. Here, using a combination of multiphoton intravital microscopy and genomic approaches, we re-examined the cutaneous reverse passive Arthus reaction and observed that IC-activated neutrophils underwent transmigration, triggered further IC formation, and transported these ICs into the interstitium, whereas neutrophil depletion drastically reduced IC formation and ameliorated vascular leakage in vivo. Thereafter, we show that these neutrophils expressed high levels of CXCL2, which further amplified neutrophil recruitment and activation in an autocrine and/or paracrine manner. Notably, CXCL1 expression was restricted to tissue-resident cell types, but IC-activated neutrophils may also indirectly, via soluble factors, modulate macrophage CXCL1 expression. Consistent with their distinct cellular origins and localization, only neutralization of CXCL2 but not CXCL1 in the interstitium effectively reduced neutrophil recruitment. In summary, our study establishes that neutrophils are able to self-regulate their own recruitment and responses during IC-mediated inflammation through a CXCL2-driven feed forward loop. PMID- 26802237 TI - Prevalence of Contact Allergy to p-Phenylenediamine in the European General Population. AB - Population-based studies on contact allergy to p-phenylenediamine (PPD) are scarce. A cross-sectional study was performed to assess the prevalence of contact allergy to PPD and its risk factors in the general population of 5 European countries. A total of 10,425 subjects were interviewed, and a random sample (n = 2,739) was patch tested to PPD. Overall, 5,286 individuals (50.9%) reported having used hair colorants at least once in their lifetime (78% female, 20% male), and 35% had used hair colorants during the last 12 months. Hair colorant avoidance because of any skin problem during the lifetime was reported by 6%. Black henna tattoos had been used by 5.5% during their lifetime. The prevalence of PPD contact allergy was 0.8% (95% confidence interval 0.6-1.0%), with no statistically significant association with gender or hair dye use. The prevalence of PPD in black henna tattoo users was 3.2% versus 0.6% in nonusers (P < 0.001). A clinically relevant positive patch test reaction to PPD related to hair coloring products was found in 0.1% (95% confidence interval 0.0-0.2%). A significant association with PPD contact allergy was observed for subjects who had black henna tattoos in their lifetime, with an age- and gender-adjusted odds ratio of 9.33 (95% confidence interval 3.45-25.26, P < 0.001). Black henna tattoos are an important risk factor for PPD contact allergy. PMID- 26802239 TI - Membrane-Tethered Intracellular Domain of Amphiregulin Promotes Keratinocyte Proliferation. AB - The epidermal growth factor receptor (EGFR) and its ligands are essential regulators of epithelial biology, which are often amplified in cancer cells. We have previously shown that shRNA-mediated silencing of one of these ligands, amphiregulin (AREG), results in keratinocyte growth arrest that cannot be rescued by soluble extracellular EGFR ligands. To further explore the functional importance of specific AREG domains, we stably transduced keratinocytes expressing tetracycline-inducible AREG-targeted shRNA with lentiviruses expressing silencing-proof, membrane-tethered AREG cytoplasmic and extracellular domains (AREG-CTD and AREG-ECD), as well as full-length AREG precursor (proAREG). Here we show that growth arrest of AREG-silenced keratinocytes occurs in G2/M and is significantly restored by proAREG and AREG-CTD but not by AREG-ECD. Moreover, the AREG-CTD was sufficient to normalize cell cycle distribution profiles and expression of mitosis-related genes. Our findings uncover an important role of the AREG-CTD in regulating cell division, which may be relevant to tumor resistance to EGFR-directed therapies. PMID- 26802240 TI - BRAF and RAS Mutations in Sporadic and Secondary Pyogenic Granuloma. AB - Pyogenic granuloma (PG) is a common benign vascular skin lesion presenting as a rapidly growing angiomatous papule. The pathogenesis of most sporadic PGs and PGs associated with port wine stains (PWSs) remains elusive. We report that of 10 PGs secondarily arisen on a PWS, 8 showed a BRAF c.1799T>A (p.(Val600Glu)) and 1 a NRAS c.182A>G (p.(Gln61Arg)) mutation. The GNAQ c.548G>A mutation was identified in the PG and in the respective underlying PWS, indicating that PGs originate from cells of the PWS. In contrast to PG, 12 papulonodular lesions, which had developed in the PWSs of seven patients, showed a RAS and BRAF wild-type status. In sporadic PG we identified the BRAF c.1799T>A mutation in 3 of 25, a BRAF c.1391G>A mutation in 1 of 25, and a KRAS c.37G>C mutation in 1 of 25. Mutation specific immunohistochemical detection of BRAF p.(Val600Glu) confirmed endothelial cells as carriers of the mutation in secondary and sporadic PG. Our study identifies the BRAF c.1799T>A mutation as a major driver mutation in the pathogenesis of, particularly, secondary PG. These data shed light on the hitherto undetermined genetic basis of PG and classify PG as a benign neoplasm. PMID- 26802242 TI - Research Techniques Made Simple: Skin Carcinogenesis Models: Xenotransplantation Techniques. AB - Xenotransplantation is a widely used technique to test the tumorigenic potential of human cells in vivo using immunodeficient mice. Here we describe basic technologies and recent advances in xenotransplantation applied to study squamous cell carcinomas (SCCs) of the skin. SCC cells isolated from tumors can either be cultured to generate a cell line or injected directly into mice. Several immunodeficient mouse models are available for selection based on the experimental design and the type of tumorigenicity assay. Subcutaneous injection is the most widely used technique for xenotransplantation because it involves a simple procedure allowing the use of a large number of cells, although it may not mimic the original tumor environment. SCC cell injections at the epidermal-to dermal junction or grafting of organotypic cultures containing human stroma have also been used to more closely resemble the tumor environment. Mixing of SCC cells with cancer-associated fibroblasts can allow the study of their interaction and reciprocal influence, which can be followed in real time by intradermal ear injection using conventional fluorescent microscopy. In this article, we will review recent advances in xenotransplantation technologies applied to study behavior of SCC cells and their interaction with the tumor environment in vivo. PMID- 26802241 TI - IL-33-Dependent Group 2 Innate Lymphoid Cells Promote Cutaneous Wound Healing. AB - Breaches in the skin barrier initiate an inflammatory immune response that is critical for successful wound healing. Innate lymphoid cells (ILCs) are a recently identified population of immune cells that reside at epithelial barrier surfaces such as the skin, lung, and gut, and promote proinflammatory or epithelial repair functions after exposure to allergens, pathogens, or chemical irritants. However, the potential role of ILCs in regulating cutaneous wound healing remains undefined. Here, we demonstrate that cutaneous injury promotes an IL-33-dependent group 2 ILC (ILC2) response and that abrogation of this response impairs re-epithelialization and efficient wound closure. In addition, we provide evidence suggesting that an analogous ILC2 response is operational in acute wounds of human skin. Together, these results indicate that IL-33-responsive ILC2s are an important link between the cutaneous epithelium and the immune system, acting to promote the restoration of skin integrity after injury. PMID- 26802243 TI - Purification and partial characterization of serine-metallokeratinase from a newly isolated Bacillus pumilus NRC21. AB - A serine metallokeratinase enzyme (30 kDa) produced by a newly isolated Bacillus strain (Bacillus pumilus NRC21) cultivated under optimized conditions in medium containing chicken feather meal was purified and characterized in a set of biochemical assays. The purification was carried out using two successive chromatographic steps; cation exchange chromatography on CM-cellulose and gel filtration on sephadex G-100 columns. The purified enzyme showed a specific activity of 2000 units/mg protein against 170 units/mg protein for crude extract with 12 fold purification. The enzymatic activity of the keratinase stimulated by (Na(+), K(+), Mg(2+)), Hg(+2) had no effect, and inhibited by entire tested cations, serine and metalloproteinase inhibitors, therefore it can be considered as a serine metalloenzyme. The optimum pH and temperature for the purified enzyme were (7.5, 8.5) and (50, 45 degrees C) when using keratin azure and azocasein as substrates, respectively. The purified enzyme was highly stable at broad pH and temperature ranged (5-10) and (20-60 degrees C), respectively and its thermoactivity and thermostability were enhanced in the presence of 5 mM Mg(+2). These results suggest that the purified keratinase may be used in several industrial applications. PMID- 26802244 TI - beta-glucans from Coriolus versicolor protect mice against S. typhimurium challenge by activation of macrophages. AB - The effects of beta-glucans from Coriolus versicolor (CVP), which are extracted from a well-known immune stimulator C. versicolor, have been demonstrated extensively in vitro and in vivo. However, until now, the phagocytic activity has not been elucidated. Hence, the objective of the present study was to identify the antibacterial activity of CVP or CVP-treated macrophages by an analysis of cell cytotoxicity, phagocytic activity, intracellular bacterial survival, macrophage activation, production of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS) in CVP-treated macrophages using flow cytometry, RT-PCR, a gentamicin protection assay, a Nitric oxide assay and an iNOS enzymatic activity assay. The results indicate that CVP-treated macrophages can phagocytize and kill bacteria, probably due to the production of NO and iNOS. More importantly, CVP-treated macrophages are effective at protecting mice against the challenge of Salmonella typhimurium. The results of this study suggest that the antibacterial effects of CVP are probably caused by the activation of innate immune cells, especially macrophages, because the activated macrophage produces NO, which kills bacteria. These phenomena indicate the possibility of CVP as a potential alternative for antibiotics against resistant bacteria. PMID- 26802245 TI - Preparation of bioactive and antimicrobial PLGA membranes by magainin II/EGF functionalization. AB - Development of dual functional materials that are capable of both reducing bacterial interaction and encouraging host tissue integration has gained importance in design of biomaterials. In this study, we prepared a bilayer poly (lactide co-glycolide) fibrous membrane with antibacterial and bioactive properties by electrospinning. The antibacterial layer was produced by covalent immobilization of antimicrobial peptide, Magainin II. The bioactive layer incorporating epidermal growth factor (EGF) molecules was subsequently electrospun on the antibacterial layer. The membranes were characterized by X-ray photoelectron spectroscopy, scanning electron microscopy and fluorescence microscopy. EGF release was detected by enzyme-linked immunosorbent assay. The antibacterial activity was tested against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The ability to support tissue cell integration was detected by using L-929 mouse fibroblasts. The dual functional membranes established enhanced antibacterial properties and increased tissue cell compatibility. This combined approach suggests a promising strategy for wound dressings, vascular grafts and dental membranes as well as catheters and fixation devices. PMID- 26802246 TI - Inhibitory effects of ionic liquids on the lactic dehydrogenase activity. AB - Ionic liquids (ILs) were widely used in scientific and industrial application and have been reported to possess potential toxicity to the environment and human health. The effects of six typical N-methylimidazolium-based ILs ([Cnmim]X, n=4, 6, 8; X=Br(-), Cl(-), BF4(-), CF3SO3(-)) on the lactic dehydrogenase (LDH) activity and the molecular interaction mechanism of ILs and the LDH were investigated with the aid of spectroscopic techniques. Experimental results showed that the LDH activity was inhibited in the presence of ILs. For the ILs with the same anion but different cations, their inhibitory ability on the LDH activity increased with increasing the alkyl chain length on the IL cation. Thermodynamic parameters, enthalpy change (DeltaH) and entropy change (DeltaS) were obtained by analyzing the fluorescence behavior of LDH with the addition of ILs. Both positive DeltaH and DeltaS suggested that hydrophobicity was the major driven force in the interaction process as expected. PMID- 26802247 TI - Step-reduced synthesis of starch-silver nanoparticles. AB - In the present process, silver nanoparticles were directly synthesized in a single step by microwave irradiation of a mixture of starch, silver nitrate, and deionized water. This is different from the commonly adopted procedure for starch silver nanoparticle synthesis in which silver nanoparticles are synthesized by preparing a starch solution as a reaction medium first. Thus, the additional step associated with the preparation of the starch solution was eliminated. In addition, no additional reducing agent was utilized. The adopted method was facile and straight forward, affording spherical silver nanoparticles with diameter below 10nm that exhibited good antibacterial activity. Further, influence of starch on the size of the silver nanoparticles was noticed. PMID- 26802248 TI - Regulation of Pathogen-Triggered Tryptophan Metabolism in Arabidopsis thaliana by MYB Transcription Factors and Indole Glucosinolate Conversion Products. AB - MYB34, MYB51, and MYB122 transcription factors are known as decisive regulators of indolic glucosinolate (IG) biosynthesis with a strong impact on expression of genes encoding CYP79B2 and CYP79B3 enzymes that redundantly convert tryptophan to indole-3-acetaldoxime (IAOx). This intermediate represents a branching point for IG biosynthesis, and pathways leading to camalexin and indole-carboxylic acids (ICA). Here we investigate how these MYBs affect the pathogen-triggered Trp metabolism. Our experiments indicated that these three MYBs affect not only IG production but also constitutive biosynthesis of other IAOx-derived metabolites. Strikingly, the PENETRATION 2 (PEN2)-dependent IG-metabolism products, which are absent in myb34/51/122 and pen2 mutants, were indispensable for full flg22 mediated induction of other IAOx-derived compounds. However, gene induction and accumulation of ICAs and camalexin upon pathogen infection was not compromised in myb34/51/122 plants, despite strongly reduced IG levels. Hence, in comparison with cyp79B2/B3, which lacks all IAOx-derived metabolites, we found myb34/51/122 an ideal tool to analyze IG contribution to resistance against the necrotrophic fungal pathogen Plectosphaerella cucumerina. The susceptibility of myb34/51/122 was similar to that of pen2, but much lower than susceptibility of cyp79B2/B3, indicating that MYB34/51/122 contribute to resistance toward P. cucumerina exclusively through IG biosynthesis, and that PEN2 is the main leaf myrosinase activating IGs in response to microbial pathogens. PMID- 26802249 TI - Regulatory and Functional Aspects of Indolic Metabolism in Plant Systemic Acquired Resistance. AB - Tryptophan-derived, indolic metabolites possess diverse functions in Arabidopsis innate immunity to microbial pathogen infection. Here, we investigate the functional role and regulatory characteristics of indolic metabolism in Arabidopsis systemic acquired resistance (SAR) triggered by the bacterial pathogen Pseudomonas syringae. Indolic metabolism is broadly activated in both P. syringae-inoculated and distant, non-inoculated leaves. At inoculation sites, camalexin, indol-3-ylmethylamine (I3A), and indole-3-carboxylic acid (ICA) are the major accumulating compounds. Camalexin accumulation is positively affected by MYB122, and the cytochrome P450 genes CYP81F1 and CYP81F2. Local I3A production, by contrast, occurs via indole glucosinolate breakdown by PEN2- dependent and independent pathways. Moreover, exogenous application of the defense hormone salicylic acid stimulates I3A generation at the expense of its precursor indol-3-ylmethylglucosinolate (I3M), and the SAR regulator pipecolic acid primes plants for enhanced P. syringae-induced activation of distinct branches of indolic metabolism. In uninfected systemic tissue, the metabolic response is more specific and associated with enhanced levels of the indolics I3A, ICA, and indole-3-carbaldehyde (ICC). Systemic indole accumulation fully depends on functional CYP79B2/3, PEN2, and MYB34/51/122, and requires functional SAR signaling. Genetic analyses suggest that systemically elevated indoles are dispensable for SAR and associated systemic increases of salicylic acid. However, soil-grown but not hydroponically -cultivated cyp79b2/3 and pen2 plants, both defective in indolic secondary metabolism, exhibit pre-induced immunity, which abrogates their intrinsic ability to induce SAR. PMID- 26802250 TI - TWISTED DWARF 1 Associates with BRASSINOSTEROID-INSENSITIVE 1 to Regulate Early Events of the Brassinosteroid Signaling Pathway. AB - A genome-wide screen for mutants showing altered brassinosteroid (BR) sensitivity or bri1-like phenotypes resulted in the identification of two new mutant alleles of TWISTED DWARF 1 (TWD1), twd1-4, and twd1-5. Previous studies indicated that TWD1, also named as ULTRACURVATA 2 or FKBP42, associates with auxin efflux transporters and is essential for their biological functions. Although earlier reports showed that BR signaling is downregulated in twd1, how TWD1 is integrated in BR signaling has not been elucidated. Here, we provide genetic and biochemical evidence demonstrating that TWD1 interacts with the BR receptor BRI1 in vivo in a BR-independent manner. Further analyses indicated that TWD1 modulates the BR signal transduction not by altering ER quality control or protein abundance of BRI1; instead, TWD1 appears to be critical in BR-induced interaction of BRI1 and its co-receptor BAK1, as well as BR-induced phosphorylation of these two proteins. These results provide better understanding of the early events of the BR signaling pathway. PMID- 26802251 TI - Binding of monovalent alkali metal ions with negatively charged phospholipid membranes. AB - We have systematically investigated the effect of various alkali metal ions with negatively charged phospholipid membranes. Size distributions of large unilamellar vesicles have been confirmed using dynamic light scattering. Zeta potential and effective charges per vesicle in the presence of various alkali metal ions have been estimated from the measured electrophoretic mobility. We have determined the intrinsic binding constant from the zeta potential using electrostatic double layer theory. The reasonable and consistent value of the intrinsic binding constant of Na(+), found at moderate NaCl concentration (10-100 mM), indicates that the Gouy-Chapman theory cannot be applied for very high (> 100mM) and very low (< 10 mM) electrolyte concentrations. The isothermal titration calorimetry study has revealed that the net binding heat of interaction of the negatively charged vesicles with monovalent alkali metal ions is small and comparable to those obtained from neutral phosphatidylcholine vesicles. The overall endothermic response of binding heat suggests that interaction is primarily entropy driven. The entropy gain might arise due to the release of water molecules from the hydration layer vicinity of the membranes. Therefore, the partition model which does not include the electrostatic contribution suffices to describe the interaction. The binding constant of Na(+) (2.4 +/- 0.1 M(-1)), obtained from the ITC, is in agreement with that estimated from the zeta potential (-2.0 M(-1)) at moderate salt concentrations. Our results suggest that hydration dynamics may play a vital role in the membrane solution interface which strongly affects the ion-membrane interaction. PMID- 26802252 TI - Suspected placenta accreta and cesarean hysterectomy: observational cohort utilizing an intraoperative decision strategy. AB - INTRODUCTION: Planned cesarean hysterectomy (CH) is recommended to minimize morbidity for suspected placenta accreta (PA), yet this ends fertility. We examined CH frequency and post-operative morbidities for suspected PA cases when an intra-operative decision strategy to perform CH was used. METHODS: Suspected PA cases were pre-operatively identified in one tertiary care center. Women were assessed intra-operatively, prior to uterine incision, for immediate CH or for attempted placental separation. We compared outcomes among women with versus without PA (surgical and/or pathologic diagnosis), and examined outcomes following immediate CH versus attempted placental separation. RESULTS: Our cohort, from 2002 to 2012, comprised 99 women with suspected PA; 54 (54.5%) had PA diagnosed by surgery/pathology, and 45 (45.5%) did not. Among women diagnoses surgically or pathologically with PA, CH was performed for 46/54 (85%); 8 women with suspected PA had successful placental separation. 27 of the 46 CH were performed immediately following uterine wall examination and 19 were performed following attempted placental separation. We received histological confirmation of the clinical placenta accreta diagnosis for 24/46 (52.2%) cases, and in 22/46 (47.8%) cases the histology did not confirm the clinical diagnosis. Surgery duration, packed cell transfusion requirement and postoperative outcomes were similar among women with PA regardless of immediate CH versus attempted placental separation, except for a higher cystotomy rates following attempted placental separation. Emergency deliveries were performed at significantly earlier gestational ages. DISCUSSION: Among women with suspected PA, an intra-operative CH decision allows some women to avoid CH. Consideration of attempted placental separation did not increase blood transfusion or post-operative complications, but was associated with a higher rate of cystotomy. PMID- 26802253 TI - Heavy metal and trace element concentrations in blood and follicular fluid affect ART outcome. AB - OBJECTIVES: To assess the effects of heavy metal and trace element concentrations in blood and follicular fluid on assisted reproductive technology cycle outcome. STUDY DESIGN: A prospective study was conducted between January 2012 and July 2012 in a university hospital infertility clinic. One hundred and one patients with unexplained infertility who underwent intracytoplasmic sperm injection using GnRH-antagonist protocol were recruited. Concentrations of four toxic metals (Cd, Pb, Hg, As) and three trace elements (Cu, Zn, Fe) were measured both in blood and follicular fluid specimens. Patients were evaluated in two groups; the study group consisted of patients with ongoing pregnancy (n=20) and the reference group consisted of patients experienced assisted reproductive technology failure, miscarriage or biochemical pregnancy (n=81). RESULTS: Demographics and cycle parameters were comparable between the groups except for median number of day 3 Grade A embryos. Statistically significant negative correlations were found between blood Pb levels and number of MII oocytes, implantation, clinical pregnancy and ongoing pregnancy rates. Results of the log binomial regression revealed 2.2% lower risk for ongoing pregnancy for each 1MUg/dL higher blood Pb concentration while holding the other variables in the model constant (RR 0.978; 95% CI 0.956-0.998; P=.041). Also, the results revealed 71.9% lower risk for ongoing pregnancy for each 1MUg/dL higher follicular fluid Cu concentration while holding the other variables in the model constant (RR 0.288; 95% CI 0.085-0.92; P=.039). CONCLUSION: Blood concentrations of Pb and follicular fluid concentrations of Cu seem to have significant impacts on assisted reproductive technology cycle outcome. PMID- 26802254 TI - Bladder injury and success rates following retropubic mid-urethral sling: TVT EXACTTM vs. TVTTM. AB - OBJECTIVE: Although placement of a retropubic mid-urethral slings (MUS) is one of the gold standard surgical treatments for stress urinary incontinence, new devices are poorly evaluated before marketing. We compared TVT-EXACTTM (TVT-E), a new device expected to reduce bladder injuries, with the historically described bottom-to-top TVTTM (TVT). STUDY DESIGN: This retrospective study compared TVT-E (n=49) and TVT (n=49). The main outcomes were the prevalence of complications (bladder injuries, immediate postoperative pain, perioperative complications, etc.) and the short-term success rate (no reported urinary leakage and negative cough test) of both MUSs. RESULTS: Minimum follow-up was 12 months. The characteristics of the two groups were comparable. The prevalence of bladder injury for TVT-E and TVT was 8% and 6%, respectively (p=1). The intensity of immediate postoperative pain (VAS/100) was lower following TVT-E than after TVT (8.0 vs. 15.9, p=0.01). The first post-void residual was increased in the TVT-E group (153.9 vs. 78.9mL, p=0.045), and there were more postoperative bladder outlet obstruction (BOO) symptoms in the TVT-E group (24% vs. 6%, p=0.02). However, there was no difference when considering only de novo BOO (14% vs. 4%, p=0.16). The prevalence of peri- and post-operative complications was equal in the two groups. The success rate was similar at 12 months of follow-up (80 vs. 82%, p=1). CONCLUSION: The prevalence of bladder injury was unchanged with TVT EXACTTM compared with TVTTM, but post-operative pain was decreased. The success rate of both retropubic MUSs was similar at 12 months of follow-up. PMID- 26802255 TI - Effect of simple and radical hysterectomy on quality of life - analysis of all aspects of pelvic floor dysfunction. AB - OBJECTIVE: The impact of simple and radical hysterectomy on all aspects of pelvic floor dysfunctions was evaluated in current study. STUDY DESIGN: This retrospective cohort study included 142 patients; 58 women (40.8%) who have undergone simple, 41 (28.8%) radical hysterectomy, and 43 (30.2%) women without any surgical intervention to serve as the control group. The validated versions of the Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire (IIQ-7), Pelvic Floor and Incontinence Sexual Impact Questionnaire (PISQ-12), Wexner Incontinence Scale score and pelvic organ prolapse quantification (POP-Q) system were used in detailed evaluation of pelvic floor dysfunction. One-way ANOVA and Pearson's chi square tests were performed in statistical analysis. RESULTS: It was found that there were significant differences in irritative and obstructive scores of UDI-6 between Type III hysterectomy group and Type I hysterectomy group. In addition, patients of Type I hysterectomy had significant higher irritative and obstructive scores than the control group. Type III hysterectomy had the most significant deteriorating effect on sexual life, based on scores of PISQ-12 compared to both Type I hysterectomy group and control group. CONCLUSION: Hysterectomy results in detrimental effects on the quality of life (QoL) regarding all aspects of pelvic floor functions especially in women of radical hysterectomy. Urinary dysfunctional symptoms like urgency, obstruction and especially sexual problems are more bothersome and difficult to overcome. The impact of hysterectomy on QoL should be investigated as a whole and may be more profound than previously thought. PMID- 26802256 TI - Increased levels of serum granzyme-B is associated with insulin resistance and increased cardiovascular risk in adolescent polycystic ovary syndrome patients. AB - OBJECTIVES: Our aim was to determine serum perforin and granzyme-B levels in adolescent PCOS patients, and to investigate whether they are associated with some of the insulin sensitivity, obesity and cardiovascular (CV) risk markers and metabolic syndrome. STUDY DESIGN: A case-control study was carried out including a total of 172 adolescents (83 PCOS patients and 89 age-matched healthy controls). Participants were recruited consecutively. Homeostasis model assessment (HOMA-IR), lipid parameters, and anthropometric measurements were determined. Serum perforin and granzyme B levels were measured by commercially available ELISA kits. HOMA-IR>3.16 was considered to indicate the presence of insulin resistance. Logistic regression analysis was applied for the predictive value of granzyme-B for increased CV risk in PCOS patients. RESULTS: As body mass index (BMI) of the PCOS patients was significantly higher than the controls (median 24.6kg/m(2) and 21.4kg/m(2), respectively, p<0.001) all parameters were evaluated after adjustment for BMI. Adolescents with PCOS had significantly higher levels of fasting glucose, insulin, HOMA-IR and granzyme-B when compared with controls. According to the results of logistic regression analysis, granzyme B levels were found to be significantly associated with increased HOMA-IR (OR=6.120, 95% CI: 2.352-15.926, p<0.001) in adolescent PCOS patients. Additionally, elevated levels of serum granzyme-B were predictive for increased CV risk in PCOS patients (OR=0.237, 95% CI: 0.091-0.616, p=0.003). CONCLUSIONS: Increased levels of serum granzyme-B are independently associated with insulin resistance and also with increased CV risk in adolescent polycystic ovary syndrome patients. PMID- 26802257 TI - Deferasirox at therapeutic doses is associated with dose-dependent hypercalciuria. AB - Deferasirox is an oral iron chelator used widely in the treatment of thalassemia major and other transfusion-dependent hemoglobinopathies. Whilst initial long term studies established the renal safety of deferasirox, there are now increasing reports of hypercalciuria and renal tubular dysfunction. In addition, urolithiasis with rapid loss of bone density in patients with beta thalassemia major has been reported. We conducted a cross-sectional cohort study enrolling 152 adult patients comprising of beta thalassemia major (81.5%), sickle cell disease (8%), thalassemia intermedia (2%), HbH disease (6.5%) and E/beta thalassemia (2%). Cases were matched with normal control subjects on age, gender and serum creatinine. Iron chelator use was documented and urine calcium to creatinine ratios measured. At the time of analysis, 88.8% of patients were receiving deferasirox and 11.2% were on deferoxamine. Hypercalciuria was present in 91.9% of subjects on deferasirox in a positive dose-dependent relationship. This was not seen with subjects receiving deferoxamine. At a mean dose of 30.2+/ 8.8mg/kg/day, deferasirox was associated with an almost 4 fold increase in urine calcium to creatinine ratio (UCa/Cr). Hypercalciuria was present at therapeutic doses of deferasirox in a dose-dependent manner and warrants further investigation and vigilance for osteoporosis, urolithiasis and other markers of renal dysfunction. PMID- 26802258 TI - Associations between hypothalamic-pituitary-adrenal axis function and peak bone mass at 20years of age in a birth cohort. AB - In older adults, high-normal circulating cortisol levels are associated with lower bone mass, but relationships between hypothalamic-pituitary-adrenal axis function and peak bone mass in young adults have not been examined. We studied 411 male and 390 female participants in the Western Australia Pregnancy Cohort (Raine) Study. At 18years of age, participants underwent a Trier Social Stress Test (TSST) with measurement of plasma and salivary cortisol at baseline and at multiple time points after stress. Cortisol responses were classified as anticipatory responder (significant fall in cortisol during the test), reactive responder (significant increase) or non-responder. At 20years, total body bone mineral content (BMC) and density (BMD) were measured by DXA. In males, after adjustment for weight, height (for BMC and bone area only), alcohol and smoking, there was a significant inverse relationship between both plasma and salivary cortisol measured at baseline in the TSST and each of BMC and BMD, such that each additional 10% of salivary cortisol was associated with reductions of 6.9g (95% CI -11.7, -2.2) in BMC, and 1.8mg/cm(2) (95% CI -3.3, -0.4) in BMD. Males classified as anticipatory responders in the TSST had 3.2% lower BMC (adjusted mean+/-SE: 3131+/-28 vs. 3233+/-18g, P=0.006) and 2.5% lower BMD (1108+/-9 vs. 1136+/-6mg/cm(2), P=0.022) than reactive responders. In females, there were no significant relationships between baseline cortisol or TSST responses and BMC or BMD in covariate-adjusted analyses. We conclude that in young males (but not females), higher circulating cortisol at the baseline of the stress test and an anticipatory responder pattern on the TSST are associated with lower total body bone mass. PMID- 26802260 TI - Improvement of phenol photodegradation efficiency by a combined g C3N4/Fe(III)/persulfate system. AB - Graphite-like C3N4 (g-C3N4) is an efficient visible-light-driven photocatalyst commonly used in dye decolorization with very poor photocatalytic efficiency for degrading recalcitrant organic pollutants, such as phenol. In this study, we designed a g-C3N4/Fe(III)/persulfate system to significantly improve the phenol photodegradation efficacy by combining photocatalysis and light Fenton interaction. The phenol removal ratio and degradation rate of the g C3N4/Fe(III)/persulfate system are 16.5- and 240-fold higher than those of individual g-C3N4 system. Sulfate radicals [Formula: see text] and H2O2 are detected in the g-C3N4/Fe(III)/persulfate system, suggesting that both radical decomposition and light Fenton interaction play important roles in phenol degradation. The efficient coupled photocatalytic system of g-C3N4 combined with Fe(III) and persulfate shows significant potential for application in large-scale degradation of environmental pollutants. PMID- 26802259 TI - Ethnic and geographic variations in the epidemiology of childhood fractures in the United Kingdom. AB - BACKGROUND: Fractures are common in childhood, and there is considerable variation in the reported incidence across European countries, but few data relating to ethnic and geographic differences within a single country. We therefore aimed to determine the incidence of childhood fractures in the United Kingdom (UK), and to describe age-, ethnicity- and region- specific variations. METHODS: The Clinical Practice Research Datalink (CPRD) contains anonymised electronic health records for approximately 7% of the UK population. The occurrence of a fracture between 1988 and 2012 was determined from the CPRD for all individuals <18years of age, and used to calculate fracture incidence rates for age, sex and ethnicity. Regional fracture incidence rates were also calculated based on general practitioner location within 14 Strategic Health Authorities (SHA) within the UK. RESULTS: The overall fracture incidence rate was 137 per 10,000 person-years (py). This was higher in boys (169 per 10,000 py) than girls (103 per 10,000 py) and white children (150 per 10,000 py) compared to those of black (64 per 10,000 py) and South Asian (81 per 10,000 py) ethnicity. Marked geographic variation in incidence was observed. The highest fracture rates were observed in Wales, where boys and girls had 1.82 and 1.97 times greater incidence, respectively, than those residing in Greater London. CONCLUSION: In the period 1988-2012, there was marked geographic and ethnic variation in childhood fracture incidence across the UK. These findings also implicate lifestyle and socio-economic differences associated with location and ethnicity, and are relevant to policy makers in the UK and internationally. PMID- 26802262 TI - Acid blue 29 decolorization and mineralization by anodic oxidation with a cold gas spray synthesized Sn-Cu-Sb alloy anode. AB - The elevated cost of anodic materials used in the anodic oxidation for water treatment of effluents undermines the real application of these technologies. The study of novel alternative materials more affordable is required. In this work, we report the application of Sn-Cu-Sb alloys as cheap anodic material to decolorize azo dye Acid Blue 29 solutions. These anodes have been synthesized by cold gas spray technologies. Almost complete decolorization and COD abatement were attained after 300 and 600 min of electrochemical treatment, respectively. The influence of several variables such as supporting electrolyte, pH, current density and initial pollutant concentration has been investigated. Furthermore, the release and evolution of by-products was followed by HPLC to better understand the oxidative power of Sn-Cu-Sb electrodes. PMID- 26802261 TI - Response of biodegradation characteristics of unacclimated activated sludge to moderate pressure in a batch reactor. AB - This study was aimed to investigate the effect of moderate pressure on unacclimated activated sludge. Process of organic degradation, variation of carbon dioxide (CO2) concentration of off-gas and characteristics of extracellular polymeric substances (EPS) of activated sludge were analyzed using pressure-atmospheric comparative experiments in bench-scale batch reactors. It was found that moderate pressure increased the degradation rate more dramatically when the biological process ran under a higher organic load with much more oxygen demand, which illuminated that applications of the pressurized method to high concentration organic wastewaters would be more reasonable and practicable. High oxygen transfer impetus increased utilization of oxygen which not only promoted the biodegradation of organics in wastewater, but also led to more EPS consumption in activated sludge. CO2 concentration of off-gas was lower in the earlier stage due to CO2 being pressed into the liquid phase and converted into inorganic carbon (IC). More CO2 emission was observed during the pressurized aerobic process 160 min later. EPS in pressurized reactor was much lower, which may be an important way of sludge reduction by pressurized technology. PMID- 26802263 TI - A new combined green method for 2-Chlorophenol removal using cross-linked Brassica rapa peroxidase in silicone oil. AB - This study proposes a new technique to treat waste air containing 2-Chlorophenol (2-CP), namely an integrated process coupling absorption of the compound in an organic liquid phase and its enzymatic degradation. Silicone oil (47V20) was used as an organic absorbent to allow the volatile organic compound (VOC) transfer from the gas phase to the liquid phase followed by its degradation by means of Cross-linked Brassica rapa peroxidase (BRP) contained in the organic phase. An evaluation of silicone oil (47V20) absorption capacity towards 2-CP was first accomplished by determining its partition coefficient (H) in this solvent. The air-oil partition coefficient of 2-CP was found equal to 0.136 Pa m(3) mol(-1), which is five times lower than the air-water value (0.619 Pam(3) mol(-1)). The absorbed 2-CP was then subject to enzymatic degradation by cross-linked BRP aggregates (BRP-CLEAs). The degradation step was affected by four parameters (contact time; 2-CP, hydrogen peroxide and enzyme concentrations), which were optimized in order to obtain the highest conversion yield. A maximal conversion yield of 69% and a rate of 1.58 mg L(-1) min(-1)were obtained for 100 min duration time when 2-CP and hydrogen peroxide concentrations were respectively 80 mg L(-1) and 6 mM in the presence of 2.66 UI mL(-1) BRP-CLEAs. The reusability of BRP-CLEAs in silicone oil was assessed, showing promising results since 59% of their initial efficiency remained after three batches. PMID- 26802264 TI - Toxicity of tributyltin (TBT) to the freshwater planarian Schmidtea mediterranea. AB - The freshwater planarian Schmidtea mediterranea, one of the best characterized animal models for regeneration research and developmental biology, is being recognised as a useful species for ecotoxicological studies. Sensitive endpoints related to planarians' behaviour and regeneration can be easily evaluated after exposure to environmental stressors. In this work the sensitivity of S. mediterranea to a gradient of environmentally relevant concentrations of TBT was studied using multiple endpoints like survival, locomotion, head regeneration and DNA damage. In addition, a feeding assay based on planarian's predatory behaviour was performed. Results indicated that TBT is toxic to planarians with LC50's of 1.87 MUg L(-1) Sn and 1.31 MUg L(-1) Sn at 48 h and 96 h of exposure respectively. Sub-lethal exposures to TBT significantly reduced locomotion and feeding, delayed head regeneration and caused DNA damage in planarians. The behavioural endpoints (feeding and locomotion) and head regeneration were the most sensitive parameters followed by DNA damage. Similar to other aquatic model organisms, S. mediterranea showed high sensitivity towards TBT exposure. Based on our results, and though further research is required concerning their sensitivity to other pollutants, the use of freshwater planarians as a model species in ecotoxicology is discussed. PMID- 26802265 TI - Efficient transformation of DDT by peroxymonosulfate activated with cobalt in aqueous systems: Kinetics, products, and reactive species identification. AB - Recently, sulfate radical ( [Formula: see text] ) based-advanced oxidation technologies (AOTs) have been attracted great attention in the remediation of contaminated soil and groundwater. In the present study, Co(2+) ions activated peroxymonosulfate (PMS) system was used to degrade 1, 1, 1-trichloro-2, 2'bis(p chlorophenyl) ethane (DDT) in aqueous solutions. It was found that DDT was efficiently degraded in the PMS/Co(II) solutions within several hours, and the degradation efficiency of DDT was dependent on the concentrations of PMS and Co(II), and the optimum molar ratio of PMS and Co(II) was 50:1. The degradation kinetics of DDT were well described with pseudo-first-order equations over a range of temperature (10-40 degrees C), and the activation energy that was calculated with Arrhenius equation was 72.3 +/- 2.6 kJ/mol. Electron paramagnetic resonance (EPR) and GC-MS techniques were applied to identify the intermediates and reactive species for DDT degradation. The results indicated that [Formula: see text] and OH were the main reactive species accounting for DDT degradation. Dichlorobenzophenone, 4-chlorobenzoic acid and benzylalcohol were the dominant intermediates for DDT degradation, and the likely degradation pathway of DDT was proposed on the basis of these identified products. Increasing pH inhibited the formation of [Formula: see text] and OH, and thus decreased the catalytic degradation of DDT. Cl(-) ion was found to significantly inhibit, while [Formula: see text] and dissolved oxygen had limited effects on DDT degradation. PMID- 26802266 TI - Sediment properties influencing the bioavailability of uranium to Chironomus dilutus larvae in spiked field sediments. AB - The partitioning of metals between dissolved and solid phases directly affects metal bioavailability to benthic invertebrates and is influenced by metal-binding properties of sediment phases. Little research has been done examining the effects of sediment properties on the bioavailability of uranium (U) to freshwater benthic invertebrates. In the present study, 18 field sediments with a wide range of properties (total organic carbon, fine fraction, cation exchange capacity, and iron content) were amended with the same concentrations of U to characterize the effects of these sediment properties on U bioavailability to freshwater midge, Chironomus dilutus. Bioaccumulation of U by C. dilutus larvae varied by over an order of magnitude when exposed to sediments spiked with 50 mg U kg(-1) d.w. (5-69 mg U kg(-1) d.w.) and 500 mg U kg(-1) d.w. (20-452 mg U kg( 1) d.w.), depending on the type of sediment. Variance in U bioaccumulation was best explained by differences in the cation exchange capacity, fine fraction (<=50 MUm particle size), and Fe content of U-spiked sediment, with generated regression equations predicting observed bioaccumulation within a factor of two. The presented regression equations offer an easy-to-apply method for accounting for the influence of sediment properties on U bioavailability in freshwater sediment, with fine fraction being the single most practical variable. This research strongly supports that risk assessments and guidelines for U contaminated sediments should not ignore the influence of sediment properties that can result in substantial differences in the bioaccumulation of U in benthic invertebrates. PMID- 26802267 TI - Restoration of carbon and microbial activity in salt-induced soil by application of peanut shell biochar during short-term incubation study. AB - For the present study, soil samples of four artificially-induced salinity gradients (S0: control, S1: 2.0, S2: 4.0, S3: 6.0 ECiw) was incubated with fine textured peanut shell biochar at various ratios (B0: control, B1: 2.5%, B2: 5.0%, B3: 10% w/w) for 30 days. At 1, 3, 7, 15, 30 days of incubation, samples were analyzed for soil carbon and selected enzyme activities. Results showed that biochar could increase soil organic carbon on application of highest rate of biochar addition (B3), hence potentially restored the saline soils by less C mineralization, and more sequestration of soil C. However, soil enzyme activities were biochar rate(s), day(s) of incubation and enzyme dependent. The lowest rate of biochar addition (B1) showed highest dehydrogenase (20.5 MUg TPF g(-1) soil h( 1)), acid phosphatase (29.1 MUg PNP g(-1) soil h(-1)) and alkaline phosphatase (16.1 MUg PNP g(-1) soil h(-1)) whereas the higher rate (B2) increased the urease (5.51 MUg urea-N g(-1) soil h(-1)) and fluorescein diacetate hydrolyzing activities (3.95 MUg fluorescein g(-1) OD soil h(-1)) in soil. All the positive changes persisted at higher levels of salinity (S2, S3) suggesting biochar amended soil may be potential for better nutrient cycling. Soil enzymes were found to be correlated with soil carbon and with each other while principal component analysis (PCA) extracted the most sensitive parameters as the acid and alkaline phosphatases and urease activities in the present experimental condition. This is the first time report of examining soil microbial environment using peanut shell biochar under a degraded (saline) soil. PMID- 26802268 TI - SimpleBox 4.0: Improving the model while keeping it simple.... AB - Chemical behavior in the environment is often modeled with multimedia fate models. SimpleBox is one often-used multimedia fate model, firstly developed in 1986. Since then, two updated versions were published. Based on recent scientific developments and experience with SimpleBox 3.0, a new version of SimpleBox was developed and is made public here: SimpleBox 4.0. In this new model, eight major changes were implemented: removal of the local scale and vegetation compartments, addition of lake compartments and deep ocean compartments (including the thermohaline circulation), implementation of intermittent rain instead of drizzle and of depth dependent soil concentrations, adjustment of the partitioning behavior for organic acids and bases as well as of the value for enthalpy of vaporization. In this paper, the effects of the model changes in SimpleBox 4.0 on the predicted steady-state concentrations of chemical substances were explored for different substance groups (neutral organic substances, acids, bases, metals) in a standard emission scenario. In general, the largest differences between the predicted concentrations in the new and the old model are caused by the implementation of layered ocean compartments. Undesirable high model complexity caused by vegetation compartments and a local scale were removed to enlarge the simplicity and user friendliness of the model. PMID- 26802269 TI - Numerical study of the effects of surface roughness on water disinfection UV reactor. AB - UV reactors are an emerging choice as a big barrier against the pathogens present in drinking water. However, the precise role of reactor's wall roughness for cross flow ultraviolet (CF-UV) and axial flow ultraviolet (AF-UV) water disinfection reactors are unknown. In this paper, the influences of reactor's wall roughness were investigated with a view to identify their role on the performance factors namely dose distribution and reduction equivalent dose (RED). Herein, the relative effects of reactor's wall roughness on the performance of CF UV and AF-UV reactors were also highlighted. This numerical study is a first step towards the comprehensive analysis of the effects of reactor's wall roughness for UV reactor. A numerical analysis was performed using ANSYS Fluent 15 academic version. The reactor's wall roughness has a significant effect on the RED. We found that the increase in RED is Reynolds number dependent (at lower value of turbulent Reynolds number the effects are remarkable). The effects of reactor's roughness were more pronounced for AF-UV reactor. The simulation results suggest that the study of reactor's wall roughness provides valuable insight to fully understand the effects of reactor's wall roughness and its impact on the flow behavior and other features of CF-UV and AF-UV water disinfection reactors. PMID- 26802270 TI - Comparison of prediction methods for octanol-air partition coefficients of diverse organic compounds. AB - The octanol-air partition coefficient (KOA) is needed for assessing multimedia transport and bioaccumulability of organic chemicals in the environment. As experimental determination of KOA for various chemicals is costly and laborious, development of KOA estimation methods is necessary. We investigated three methods for KOA prediction, conventional quantitative structure-activity relationship (QSAR) models based on molecular structural descriptors, group contribution models based on atom-centered fragments, and a novel model that predicts KOA via solvation free energy from air to octanol phase (DeltaGO(0)), with a collection of 939 experimental KOA values for 379 compounds at different temperatures (263.15-323.15 K) as validation or training sets. The developed models were evaluated with the OECD guidelines on QSAR models validation and applicability domain (AD) description. Results showed that although the DeltaGO(0) model is theoretically sound and has a broad AD, the prediction accuracy of the model is the poorest. The QSAR models perform better than the group contribution models, and have similar predictability and accuracy with the conventional method that estimates KOA from the octanol-water partition coefficient and Henry's law constant. One QSAR model, which can predict KOA at different temperatures, was recommended for application as to assess the long-range transport potential of chemicals. PMID- 26802271 TI - Volatile-organic molecular characterization of shale-oil produced water from the Permian Basin. AB - Growth in unconventional oil and gas has spurred concerns on environmental impact and interest in beneficial uses of produced water (PW), especially in arid regions such as the Permian Basin, the largest U.S. tight-oil producer. To evaluate environmental impact, treatment, and reuse potential, there is a need to characterize the compositional variability of PW. Although hydraulic fracturing has caused a significant increase in shale-oil production, there are no high resolution organic composition data for the shale-oil PW from the Permian Basin or other shale-oil plays (Eagle Ford, Bakken, etc.). PW was collected from shale oil wells in the Midland sub-basin of the Permian Basin. Molecular characterization was conducted using high-resolution solid phase micro extraction gas chromatography time-of-flight mass spectrometry. Approximately 1400 compounds were identified, and 327 compounds had a >70% library match. PW contained alkane, cyclohexane, cyclopentane, BTEX (benzene, toluene, ethylbenzene, and xylene), alkyl benzenes, propyl-benzene, and naphthalene. PW also contained heteroatomic compounds containing nitrogen, oxygen, and sulfur. 3D van Krevelen and double bond equivalence versus carbon number analyses were used to evaluate molecular variability. Source composition, as well as solubility, controlled the distribution of volatile compounds found in shale-oil PW. The salinity also increased with depth, ranging from 105 to 162 g/L total dissolved solids. These data fill a gap for shale-oil PW composition, the associated petroleomics plots provide a fingerprinting framework, and the results for the Permian shale-oil PW suggest that partial treatment of suspended solids and organics would support some beneficial uses such as onsite reuse and bio-energy production. PMID- 26802272 TI - Spatial-temporal characteristics and determinants of PM2.5 in the Bohai Rim Urban Agglomeration. AB - Ambient particulate matter (PM) pollution of China has become a global concern and has great impact on air quality and human health. This paper adopts the PM2.5 concentration data obtained from 241 newly located observation points in the Bohai Rim Urban Agglomeration (BRUA), as well as economic, urban and industrial working population data in the study area, revealing the spatio-temporal distribution of PM2.5 and its determinants with the help of a spatial data model. The results indicate that: 1) The BRUA was the core area of PM2.5 pollution in China in 2014, the average PM2.5 concentration of which reached 74 MUg/m(3), which is 13 MUg/m(3) higher than the country average (61 MUg/m(3)); 2) The PM2.5 concentration distribution had a characteristic of high in winter and autumn but low in spring and summer, presenting a U-shaped monthly profile and a U-impulse type daily profile; 3) The urban PM2.5 concentrations showed obvious spatial variation and agglomeration. The highest hot-spot was observed in spring, while the lowest was in summer. High concentration cities were mainly located in southern Hebei and western Shandong, and low concentration cities were in the coastal area around the Bohai Sea and the mountainous areas in northern Hebei. High hot-spot areas demonstrated an M-shaped change, with two cycles of advance and retreat from west to east. 4) The Geographically weighted regression (GWR) model shows that the GDP per capita, urbanization rate and construction of the cities were closely related to PM2.5 concentrations in the BRUA. PMID- 26802273 TI - Finding robust descriptive features for the characterization of the coarsening dynamics of three dimensional whey protein foams. AB - HYPOTHESIS: Understanding the coarsening behavior of foams is of great interest for their deliberate design. In order to systematically quantify the influence of surfactants and other chemical parameters, identifying robust descriptive features of observed foam aging dynamics is essential. Existing coarsening theories for both wet and dry foams provide concise models with respective descriptive parameters. EXPERIMENT: Multiple micro computed tomography scans of moderately wet polydisperse beta-Lactoglobulin foam are recorded over a period of 15min. The growth behavior of a large fraction of about 5*10(4) pores that constitute the imaged volume is individually observed and statistically analyzed as a function of pore radius as well as number of neighboring pores. FINDINGS: The three-dimensional analog of von Neumann's law for dry foams by Glazier is confirmed as a suiting empirical model, whereby a critical number of 13+/-7 neighbors and a diffusion coefficient of (1.8+/-0.8)*10(-11)m(2)/s are found for an exemplary sample. The pores growth can as well be related to their radius by means of Lemlich's coarsening model for wet foams though, whereby a critical radius marking the transition between shrinkage and growths is found to be Rc=(300+/-85)MUm. Although different, both models fit similarly well given the broad variance of the observed growth rates. PMID- 26802274 TI - Effect of forced convection on the collision and interaction between nanoparticles and ultramicroelectrode. AB - Detection of nanoparticle (NP) collision events at ultramicroelectrode (UME) has emerged as a new methodology for the investigation of single NP in recent years. Although the method was widely employed, some fundamental knowledge such as how the NP moves to and interacts with the UME remain less understood. It was generally recognized that the recorded rate of collision was determined by diffusion that should follow Fick's first law. However, significant lower collision frequency compared with that of predicted by theory were frequently reported. Experiments carried out by us suggest that the collision frequency will increase dramatically if forced convection (stir or flow injection) is applied during detection. Furthermore, the collision frequency gradually increases to a maximum and then decreases, along with the increase of the convection intensity. This phenomenon is interpreted as follows: (a) there are two steps for a freely moving NP to generate a detectable collision signal. The first step is the move of NP from bulk solution to the surface of the UME which is mass transfer limited; the second step is the landing of NP on the surface of UME which is affected by many factors and is the critical step; (b) there is a barrier that must be overcame before the contact between freely moving NP and UME. Forced convection with moderate intensity can not only increase the mass transfer rate but also help to overcome this barrier and thus enhance the collision frequency; (c) the landing of NP on the surface of UME can be suppressed by stronger convections, because NP will be swept away by hydrodynamic force. PMID- 26802275 TI - Modeling the yield strength of polymer nanocomposites based upon nanoparticle agglomeration and polymer-filler interphase. AB - In this paper, some models for yield strength of polymer nanocomposites are developed to determine the properties of interphase and agglomerated nanoparticles. In this regard, "Bagg" parameter is defined assuming the agglomerates size (Dagg) and interphase properties. Additionally, the influences of "Bagg" and "Dagg" on the thickness and strength of interphase are evaluated by the developed equations. The agglomeration of nanoparticles causes contradictory effects on interphase properties in samples with different levels of interfacial bonding. Also, "Bagg" more depends to interphase properties compared to "Dagg". It is found that upon increasing in "Bagg" and "Dagg", the strength of interphase improves and reaches the most level at the highest values of "Bagg" and "Dagg". Therefore, controlling the levels of "Bagg" and "Dagg" is crucial to obtain a strong interphase. PMID- 26802276 TI - BET adsorption reaction model based on the pseudo steady-state hypothesis for describing the kinetics of adsorption in liquid phase. AB - A multilayer adsorption reaction model in liquid phase based on BET isotherm fundamentals has been developed from the pseudo steady-state hypothesis of adsorption on the accumulating adsorbate layers. The model accurately reproduces the adsorption isotherms and kinetic profiles of different adsorption systems reported in the literature, and especially those of mesoporous carbon materials used to adsorb organic compounds in aqueous solutions. The kinetic rate constant evaluated for each of the adsorption systems permitted them to be sorted according to the adsorption rate, regardless of the operation parameters employed in the experiments. The model also allowed the effect of the equilibrium parameters and operation variables on the adsorption rate to be analyzed. The analysis yielded similar trends to those reported in literature. PMID- 26802277 TI - Exploitation of redox discrepancy in leukemia cells by a reactive oxygen species nanoscavenger for inducing cytotoxicity in imatinib resistant cells. AB - Chronic myeloid leukemia (CML) has been the hub of exhilarating progress in cancer therapy with the advent of imatinib mesylate. However, therapeutic selectivity and drug resistance are two major issues in imatinib based leukemia therapy prompting development of strategies to surmount imatinib resistance for effective CML therapy. Growing evidences advocate that, cancer cells exhibit augmented intrinsic reactive oxygen species (ROS), due to oncogenic stimulation, amplified metabolic activity, and mitochondrial dysfunction. Since ROS activates multidrug resistant proteins in CML cells, we hypothesized that an herbal molecule having ROS scavenging property may therefore enhance imatinib induced cell death in drug resistant cells by counteracting ROS mediated drug resistance. In the present study, we document to explore an approach to simultaneously deliver two drugs (imatinib, an anticancer drug for CML therapy and curcumin a ROS scavenger) using poly (lactide-co-glycolide) (PLGA) nanoparticles for drug resistant CML cells. Such a combinational approach will help to enhance the therapeutic efficacy of imatinib by utilizing ROS scavenging properties of curcumin in imatinib resistant cell line thereby sensitizing them to chemotherapy by activating alternative modalities of cell death. PMID- 26802279 TI - Selective co-deposition of anionic silica particles at hydrophobic surfaces from formulations of oppositely charged polymers and surfactants. AB - The surface-selective surface deposition of anionic hydrophilic silica particles from aqueous polymer-surfactant formulations was investigated by in-situ null ellipsometry. The formulations, with or without silica particles, contained anionic sodium dodecylsulfate (SDS) and a cationic polymer, cationic hydroxyethyl cellulose (cat-HEC) or a copolymer of acrylamide and methacrylamidopropyl trimethylammonium chloride (AAm/MAPTAC). Surface deposition from the formulations onto model surfaces of either anionic hydrophilic, or hydrophobized, silica was induced by controlled dilution of the formulations into the coacervation region, and was monitored with time by ellipsometry. The dilution simulated a rinsing process in a typical application. In all cases a steady-state surface layer remained after extensive dilution. An enhanced deposition from the silica containing formulations was found on the hydrophobized silica surface, indicating a substantial co-deposition of silica particles. Much less co-deposition, or none at all, was found on hydrophilic silica. The opposite trend, enhanced co deposition on hydrophilic silica, was previously found in similar experiments with hydrophobic silicone oil droplets as co-deposants (Clauzel et al., 2011). The amphiphilic cationic polymers evidently favor a "mismatched" co-deposition of anionic particles to hydrophobic surfaces, or vice versa. The findings suggest a strategy for surface-specific delivery of particles to surfaces. PMID- 26802278 TI - Silane grafted chitosan for the efficient remediation of aquatic environment contaminated with arsenic(V). AB - HYPOTHESIS: Chitosan, naturally abundant biomaterial showed an insignificant affinity toward arsenate. The incorporation of organosilane could improve the physical and chemical properties of chitosan for the efficient removal of arsenate from aquatic environment. EXPERIMENT: The hybrid materials were obtained by grafting the natural biopolymer chitosan with 3-mercaptopropyl trimethoxysilane (CHMS) and trimethoxy-octylsilane (CHTS). The hybrid materials along with bare chitosan were characterized with SEM-EDX, FT-IR and BET specific surface area analyses and the solid materials were further employed in the efficient remediation of aqueous solutions contaminated with As(V) under batch and column reactor operations. FINDINGS: The hybrid materials showed an extremely high percentage of As(V) removal compared to bare chitosan within a wide range of pH. As(V) was aggregated rapidly onto the solid surfaces and relatively high percent removal of As(V) was achieved in a wide range of As(V) initial concentrations. Moreover, As(V) was bound with, relatively, weaker forces and forming an 'outer sphere complexes' at the surface of solids. The presence of co existing ions could not significantly affect the removal of As(V) from aqueous solutions. Furthermore, breakthrough data confirmed that these two hybrid materials possessed significantly high loading capacity of As(V) even under dynamic conditions. PMID- 26802280 TI - Long-term effects of changes in Swedish alcohol policy: can alcohol policies effective during adolescence impact consumption during adulthood? AB - AIMS: To assess long-term effects of alcohol policy in Sweden by estimating the differences between cohorts growing up during periods with liberal alcohol policies and a cohort growing up during a period with restrictive alcohol policy. DESIGN: The data come from repeated cross-sectional surveys conducted in Sweden between 2002 and 2013, and were collected monthly using telephone interviews with a nationally representative sample. Cohorts were constructed by identifying periods when alcohol policy differed between being more liberal or more restrictive. The liberal-period cohorts were merged into one and compared with the restrictive-period cohort. SETTING: Sweden. PARTICIPANTS: A total of 127 480 adult Swedes born between 1951 and 1989. MEASUREMENTS: Monthly volume of alcohol consumption in litres of pure alcohol derived from a beverage-specific graduated quantity-frequency scale. FINDINGS: Relative to the liberal-period reference cohorts (who turned 15 between 1966 and 1977 or 1992 and 2004), the cohort that grew up during a period with restrictive alcohol policy (turning 15 between 1978 and 1991) was found to have lower alcohol consumption (coeff. = -0.039: confidence interval -0.050 to -0.027: P < 0.001). The mean volume for the liberal and restrictive cohorts across all survey years was 0.42 and 0.38 litres of pure alcohol, respectively. Consumption development for the period 2002-13 was, however, the same for both cohort groups. CONCLUSIONS: Men and women in Sweden who grew up during a period with more restrictive alcohol policies currently drink less alcohol than those who grew up during periods with more liberal policies. PMID- 26802281 TI - Severe hypoxia during incremental exercise to exhaustion provokes negative post exercise affects. AB - The post-exercise emotional response is mainly dependent on the intensity of the exercise performed; moderate exercise causes positive feelings, whereas maximal exercise may prompt negative affects. Acute hypoxia impairs peak O2 uptake (VO2peak), resulting in a shift to a lower absolute intensity at the point of exhaustion. Hence, the purpose of the study was to examine whether a severe hypoxic stimulus would influence the post-exercise affective state in healthy lowlanders performing an incremental exercise to exhaustion. Thirty-six male lowlanders performed, in a counter-balanced order and separated by a 48-h interval, two incremental exercise trials to exhaustion to determine their VO2peak, while they were breathing either room air (AIR; FiO2: 0.21), or a hypoxic gas mixture (HYPO; FiO2: 0.12). Before and immediately after each trial, subjects were requested to complete two questionnaires, based on how they felt at that particular moment: (i) the Profile of Mood States-Short Form, and (ii) the Activation Deactivation Adjective Check List. During the post-exercise phase, they also completed the Multidimensional Fatigue Inventory. VO2peak was significantly lower in the HYPO than the AIR trial (~15%; p<0.001). Still, after the HYPO trial, energy, calmness and motivation were markedly impaired, whereas tension, confusion, and perception of physical and general fatigue were exaggerated (p<=0.05). Accordingly, present findings suggest that an incremental exercise to exhaustion performed in severe hypoxia provokes negative post exercise emotions, induces higher levels of perceived fatigue and decreases motivation; the affective responses coincide with the comparatively lower VO2peak than that achieved in normoxic conditions. PMID- 26802283 TI - Concordance with known causal effects is a potential validity measure for observational studies. PMID- 26802282 TI - Chemical and toxicological characteristics of conventional and low-TSNA moist snuff tobacco products. AB - Use of smokeless tobacco products (STPs) is associated with oral cavity cancer and other health risks. Comprehensive analysis for chemical composition and toxicity is needed to compare conventional and newer STPs with lower tobacco specific nitrosamines (TSNAs) yields. Seven conventional and 12 low-TSNA moist snuff products purchased in the U.S., Sweden, and South Africa were analyzed for 18 chemical constituents (International Agency for Research on Cancer classified carcinogens), pH, nicotine, and free nicotine. Chemicals were compared in each product using Wilcoxon rank-sum test and principle component analysis (PCA). Conventional compared to low-TSNA moist snuff products had higher ammonia, benzo[a]pyrene, cadmium, nickel, nicotine, nitrate, and TSNAs and had lower arsenic in dry weight content and per mg nicotine. Lead and chromium were significantly higher in low-TSNA moist snuff products. PCA showed a clear difference for constituents between conventional and low-TSNA moist snuff products. Differences among products were reduced when considered on a per mg nicotine basis. As one way to contextualize differences in constituent levels, probabilistic lifetime cancer risk was estimated for chemicals included in The University of California's carcinogenic potency database (CPDB). Estimated probabilistic cancer risks were 3.77-fold or 3-fold higher in conventional compared to low-TSNA moist snuff products under dry weight or under per mg nicotine content, respectively. In vitro testing for the STPs indicated low level toxicity and no substantial differences. The comprehensive chemical characterization of both conventional and low-TSNA moist snuff products from this study provides a broader assessment of understanding differences in carcinogenic potential of the products. In addition, the high levels and probabilistic cancer risk estimates for certain chemical constituents of smokeless tobacco products will further inform regulatory decision makers and aid them in their efforts to reduce carcinogen exposure in smokeless tobacco products. PMID- 26802284 TI - Effect of storage conditions on subpopulations of peripheral blood T lymphocytes isolated from naive cattle and cattle infected with foot-and-mouth disease virus. AB - BACKGROUND: Immunophenotyping of blood lymphocytes by flow cytometry is important in infectious disease research. In animal experiments and other longitudinal studies, the processing, prompt staining, and analysis of fresh samples is a logistical challenge and daily assay variation can confound data interpretation. OBJECTIVE: This study examined the feasibility of cryopreservation and deferred analysis of bovine peripheral blood T lymphocytes from normal or infected animals. METHODS: Peripheral blood mononuclear cells were collected from 4 naive Holstein steers and 4 steers infected with foot-and-mouth-disease virus serotype Asia1. Identical aliquots were labeled and analyzed immediately, labeled for deferred analysis, or stored at -70 degrees C or over liquid nitrogen for up to 3 weeks before labeling. RESULTS: Freezing of unlabeled cells induced statistically significant changes in phenotypic recognition. In infected animals, the gammadelta T-cell population increased by 28% and CD8(+) alphabetaT cells by 32%, while total CD3(+) cells decreased by 16%, and CD4(+) alphabetaT cells decreased by 12%. Subsequent storage of frozen cells for the duration of the study, however, had no significant effect. There was less than 20% relative change in subpopulation sizes, and storage at -70 degrees C or over liquid nitrogen was equivalent. CONCLUSIONS: Depending on the objectives and practical limitations of a study, deferred labeling of peripheral blood lymphocytes can be a viable option. Although frozen storage of lymphocytes can introduce some artifactual distortion of relative cell populations, frozen cells can be maintained in storage until all samples in a longitudinal study can be analyzed in batch under standardized conditions and without introducing further bias. PMID- 26802285 TI - Nocturnal and Circadian Rhythm of Blood Pressure Is Associated with Renal Structure Damage and Function in Patients with IgAN. AB - BACKGROUND AND AIMS: Abnormal circadian rhythm of blood pressure (BP) is closely related to target organ damage in hypertension. However, the association between abnormal circadian rhythm of BP and renal injury is not clear. We investigated whether renal injury is associated with nocturnal BP and circadian rhythm of BP in Chinese IgAN patients. METHODS: Clinic and 24 h ambulatory BP monitoring data were obtained from 330 Chinese IgAN patients with mean 24 h BP < 130/80 and mean daytime BP < 135/85 mmHg. Renal histopathological injury was determined according to the Oxford classification of IgAN. RESULTS: Among the 330 IgAN subjects, 35.8% suffered from nocturnal hypertension, 61.5% had abnormal circadian BP, and 27% had nocturnal hypertension with a nondipping pattern. Compared with nocturnal normotensive patients, patients with nocturnal hypertension had significantly higher levels of blood cystatin C, blood uric acid, and lower estimated glomerular filtration rate (eGFR), and significantly a higher mean renal tissue injury score. The nondipping hypertensive group had significantly higher nocturnal diastolic and systolic BP, blood uric acid, and glomerulosclerosis rates, whereas eGFR was lower. In nondipping hypertensive patients, urinary sodium excretion and renal tissue injury scores were significantly higher than dipping patients. Nocturnal hypertension and abnormal circadian BP correlated with renal tissue injury, renal interstitial fibrosis, and aortic arch atherosclerosis. CONCLUSION: Abnormal circadian rhythm of BP and nocturnal hypertension are common clinical manifestations in Chinese IgAN patients with normal mean 24 h BP. Abnormal circadian BP and nocturnal hypertension may accelerate IgAN progression by inducing renal dysfunction and histopathological damage. PMID- 26802286 TI - Oncological Characteristics of Radiological Invasive Adenocarcinoma with Additional Ground-Glass Nodules on Initial Thin-Section Computed Tomography: Comparison with Solitary Invasive Adenocarcinoma. AB - INTRODUCTION: We aimed to evaluate the oncological outcomes of radiological invasive adenocarcinoma with additional ground-glass nodules (AGGNs) on initial thin-section computed tomography (CT). METHODS: We examined 473 patients with surgically resected clinical stage IA lung adenocarcinoma showing a radiological invasive appearance on thin-section CT. Radiological invasiveness was defined as a solid tumor with a consolidation tumor ratio of at least 0.5 but no greater than 1.0 on thin-section CT. RESULTS: Ninety patients (19%) had dominant invasive adenocarcinoma (DA) with AGGNs, whereas 383 (81%) had solitary invasive adenocarcinoma (SA). DA showed a significantly lower maximum standardized uptake value of (18)F-fluorodeoxyglucose on positron emission tomography (p = 0.0086), higher frequency of radiological part solid tumor (p = 0.0232) and histological lepidic predominant tumor (p = 0.0015), and lesser presence of nodal involvement (p = 0.0350) and lymphovascular invasion (p = 0.0001) than with SA. Surgically resected AGGNs were shown to be pathologically atypical adenomatous hyperplasia in 17% of patients, adenocarcinoma in situ in 53%, and minimally invasive adenocarcinoma in 21%. Furthermore, the 5-year overall survival of DA with AGGNs was better than that of SA, and the difference was significant (92.2% versus 79.9%, p = 0.0323). On the basis of a multivariate analysis, tumor size, maximum standardized uptake value, and consolidation status of DA/SA were significant prognostic factors of survival for all patients (p = 0.0039, 0.0236, and 0.0385, respectively), whereas the presence of AGGNs was not associated with poor overall survival (p = 0.4809). CONCLUSION: DA accompanied by AGGNs showed an oncologically less invasive nature compared with SA. Presence of AGGNs is not related to poor prognosis, and is neither indicative of an advanced stage nor a contraindication to surgical resection in patients with clinical stage IA radiological invasive adenocarcinoma. PMID- 26802288 TI - Insulators and domains of gene expression. AB - The genomic organization into active and inactive chromatin domains imposes specific requirements for having domain boundaries to prohibit interference between the opposing activities of neighbouring domains. These boundaries provide an insulator function by binding architectural proteins that mediate long-range interactions. Among these, CTCF plays a prominent role in establishing chromatin loops (between pairs of CTCF binding sites) through recruiting cohesin. CTCF mediated long-range interactions are integral for a multitude of topological features of interphase chromatin, such as the formation of topologically associated domains, domain insulation, enhancer blocking and even enhancer function. PMID- 26802287 TI - Development of invariant natural killer T cells. AB - Invariant natural killer T (iNKT) cells develop into functionally distinct subsets. Each subset expresses a unique combination of transcription factors that regulate cytokine gene transcription upon activation. The tissue distribution and localization within tissues also varies between subsets. Importantly, the relative abundance of the various subsets is directly responsible for altering several immunological parameters, which subsequently affect the immune response. Here, I review recent advances in our understanding of the molecular regulation of iNKT cell subset development. PMID- 26802289 TI - Unique Case of Takayasu Arteritis with Severe Distal Aortic Stenosis and Iliac Thrombosis. AB - Takayasu arteritis is a rare, chronic large vessel vasculitis of unknown etiology which predominantly affects women younger than 40 years of age. Symptoms are highly variable based on the location and extent of the stenosis, arterial occlusion, aneurysm, and thrombosis. Diagnosis is based on clinical presentation, relevant laboratory work-up, and imaging findings of wall thickening and stenosis of medium and large vessels. Management includes glucocorticoid therapy, frequently paired with adjunctive immunosuppressants, and sometimes surgical intervention in severe cases. Here, we present a unique case of Takayasu arteritis with critical distal aortic stenosis with very severe wall thickening involving the bilateral common iliac artery and leading to left iliac artery thrombosis. Based on our literature review, our article represents a very rare presentation of Takayasu arteritis with severe iliac artery thrombosis. PMID- 26802290 TI - Endovascular Treatment of Atherosclerotic Iliac Stenosis: Local and Systemic Complications of the Open Brachial Access. AB - BACKGROUND: The femoral access is the approach of reference for iliac angioplasty. In the current context of an early ambulation and a minimization of in-hospital stay period, the brachial access seems to be an appropriate approach, especially that long and small diameter equipments are available. Furthermore, it is extremely useful in case of inappropriate or unavailable femoral access. The aim of this study was to evaluate the complication risk factors of the brachial approach in the treatment of iliac stenosis. METHODS: Between January 2012 and December 2013, we performed 281 iliac transluminal angioplasties of which 57 (20%) consecutive left brachial artery accesses were performed in 54 patients. The choice of brachial access was justified in 68% of the cases by an unavailable femoral access, in 29% of the cases by the presence of bilateral iliac lesions, and in 3% of the cases after failure of retrograde femoral approach. RESULTS: The patients were of a male majority (81%) with a mean age of 66 +/- 9 years. The procedure was performed under local anesthesia in 65% of the cases. No upper limb ischemia or nervous complications had been reported. No cerebrovascular stroke has been identified. One patient presented with dysarthria associated with disorientation without the presence of cerebrovascular ischemia on the computed tomography scan and on the magnetic resonance imaging. There were 3 major hematomas at the brachial access site, which required reoperation; these 3 patients were on dialysis. There was no statistically significant relationship between a complication occurrence and the diameter or length of the introducer. The mean in-hospital stay period was 2 days. The procedure was considered successful in 91% of the cases. We reported 5 cases of failure: 4 of which was due to a difficulty in crossing the lesion and 1 due to a very short material. The only significant risk factor of failure was the thrombosis of the iliac axis (odds ratio 23.3, 95% confidence interval 2.5-264.6, P = 0.003). CONCLUSIONS: The femoral access remains the recommended approach for the treatment of iliac occlusive lesions. However, brachial artery access seems to provide a safe and secure alternative approach for patients when femoral artery access is unavailable. It allows a rapid ambulation and an ambulatory care. PMID- 26802291 TI - Mycotic Aneurysm following a Dog Bite: The Value of the Clinical History and Molecular Diagnostics. AB - A 63-year-old Caucasian taxi driver presented with a 3-week history of malaise, night sweats, 7 kg weight loss, generalized arthralgia, and persistent mid-lower abdominal pain. Blood inflammatory markers were raised, and a computed tomography scan demonstrated an irregular degeneration of the infrarenal aorta, with a differential diagnosis including aortic infection. An urgent type IV thoracoabdominal aneurysm repair was performed with a rifampicin-soaked aortic tube graft during an open procedure. No organisms were grown from multiple peripheral blood cultures or culture of the affected aorta. However, subsequent 16S ribosomal polymerase chain reaction analysis of the resected aorta identified Capnocytophaga canimorsus as the causative organism-a commensal that lives in the mouth of dogs and cats. The patient subsequently gave a history of multiple bites from his pet dog over recent months-the likely source of infection. He was treated with 8 weeks of intravenous antibiotics before switching to oral antibiotics for an additional 6 weeks. PMID- 26802292 TI - Successful Reconstruction of Asymptomatic Bilateral External Carotid Artery Aneurysms. AB - True aneurysms of the external carotid artery (ECA) are extremely rare with an unknown incidence and natural history. We present the successful operative management of an asymptomatic 65-year-old man found to have bilateral internal carotid artery stenosis and bilateral ECA aneurysms. His bilateral carotid arteries were reconstructed with bifurcated interposition grafts in a staged fashion. The patient recovered without sequelae and continues to be asymptomatic 1 year after reconstruction. We present the operative management of this rare case. PMID- 26802294 TI - Hybrid Treatment of Large Brachial Artery Pseudoaneurysms. AB - BACKGROUND: Conventional surgical treatment of brachial artery pseudoaneurysms (BAPs) includes aneurysm excision/opening and subsequent arterial reconstruction with different options depending on the extent of the arterial deficit. Endovascular repair of BAPs with stent grafting has also been reported but published experience remains limited. In this report, we present our experience with a novel hybrid approach consisting of primary endovascular aneurysm exclusion with a stent graft and subsequent open surgical evacuation of pseudoaneurysm content for decompression of adjacent structures. METHODS: This study included all patients who underwent hybrid repair of a BAP within the period 2005-2014 in our institution. Data were collected retrospectively. RESULTS: During the study period a total of 5 patients with iatrogenic BAPs were treated. Mean BAP diameter was 58 +/- 4.9 mm. Technical success was 100%. Thirty day mortality was null. No major perioperative complications were noted. Hand ischemia and neurological symptoms were reversed in all patients after the procedure. During follow-up (median 24 months, range 6-60 months) all stent grafts remained patent and no aneurysm relapse was noticed. No signs of stent graft infection were noticed in any of the patients and no reintervention was needed. CONCLUSIONS: Primary endovascular exclusion of BAPs with a stent graft followed by surgical evacuation of pseudoaneurysm sac content is associated with good early and mid-term results in this limited experience. Larger patient cohorts are required for further evaluation of this technique. PMID- 26802293 TI - Safety of Carotid Revascularization in Symptomatic Patients with less than 70 Years. AB - BACKGROUND: Age is a main risk factor for stroke and perioperative risk. This study aims to analyze the effect of age by symptomatic status in young patients receiving carotid revascularization. METHODS: Consecutive carotid revascularization procedures performed during the period 2001-2009 were reviewed. Patients were analyzed by age using the 70-year threshold as suggested by trials. Primary end point was perioperative stroke or death rate. Secondary end points included survival and late stroke incidence at 6 years. RESULTS: A total of 2,196 procedures (1,080 by carotid artery stenting [CAS] and 1,116 by carotid endarterectomy [CEA]) were analyzed. Symptomatic patients (n = 684) showed higher perioperative stroke or death risks (24 of 684 [3.5%] versus 29 of 1,512 [1.9%], odds ratio [OR] 1.8; 95% confidence interval [CI] 1.07-3.22; P = 0.034) and lower 6-year survival (74% vs. 82%, P < 0.0001) or freedom from late stroke (93% vs. 97%, P = 0.001) when compared with asymptomatic patients with similar differences detected within CEA or CAS procedure. Overall 949 procedures were in patients with 70 years or less at the time of intervention (500 CEA and 449 CAS); 282 were in patients symptomatic for minor stroke or transient ischemic attack within 6 months before revascularization. For young symptomatic patients, primary end point rates were <2.5% after both CEA and CAS procedure. Perioperative stroke or death rates were 2.4% in symptomatic versus 1.5% in asymptomatic (4 of 170 vs. 5 of 330; OR 1.57; 95% CI 0.42-5.91; P = 0.50) within the CEA group and 1.8% in symptomatic versus 1.2% in asymptomatic (2 of 112 vs. 4 of 337; OR 1.51; 95% CI 0.27-8.38; P = 0.64) within the CAS group. At 6 years, symptomatic young patients showed survival (89.5% vs. 89%, P = 0.76) and freedom from late stroke (97% vs. 98%, P = 0.56) rates comparable to those found in asymptomatic patients, with similar incidences after CAS or CEA procedure. CONCLUSIONS: Outcomes after carotid revascularization are related to patients' age. At younger ages (<70 years), after carotid revascularization, symptomatic patients show low perioperative risks of stroke or death, comparable with those in asymptomatic patients. The same, 2.5% or lower, threshold for perioperative stroke or death risk related to asymptomatic carotid procedures must be applied today to symptomatic patients when younger than age of 70 years. PMID- 26802295 TI - The Use of the Angiosome Concept for Treating Infrapopliteal Critical Limb Ischemia through Interventional Therapy and Determining the Clinical Significance of Collateral Vessels. AB - BACKGROUND: The purpose of this study was to evaluate the clinical significance of the involvement of collateral vessels in interventional therapy based on the angiosome concept for infrapopliteal critical limb ischemia (CLI). METHODS: We enrolled 486 patients with unilateral infrapopliteal CLI (Rutherford Stage 5 or 6) treated at 2 hospitals from January 2005 to December 2014. Using the angiosome concept, the patients were categorized into 3 groups: the direct revascularization (DR) group, the indirect revascularization through collaterals (IR-tc) group, and the indirect revascularization without collaterals (IR-wc) group. The data from 1 year of follow-up after the initial surgery were analyzed for all 3 groups. RESULTS: During the 1-year follow-up, the unhealed ulcer rate of the IR-wc group was significantly higher than that of the DR group (83.4% vs. 31.7%, P < 0.001) and the IR-tc group (83.4% vs. 34.8%, P < 0.001). Furthermore, the limb salvage rate of the IR-wc group was significantly lower than that of the DR group (70.4% vs. 89.2%, P < 0.001) and the IR-tc group (70.4% vs. 85.4%, P = 0.0013). However, there were no differences in the unhealed ulcer rate or the limb salvage rate between the DR group and the IR-tc group (31.7% vs. 34.8%, P = 0.096 and 89.2% vs. 85.4%, P = 0.2834, respectively). In addition, within the IR wc group, the unhealed ulcer rate of diabetic patients was higher than that of patients without diabetes (90.0% vs. 74.6%, P = 0.0116), but there was no difference in the limb salvage rate between diabetic and nondiabetic patients. No differences in the unhealed ulcer rate or the limb salvage rate were found between diabetic and nondiabetic patients in the other 2 groups. CONCLUSIONS: Following the angiosome model of perfusion for endovascular therapy, directly revascularizing the feeding artery and indirectly achieving revascularization through collaterals can effectively prompt the healing of ulcers and decrease the amputation rate in patients with infrapopliteal CLI. Collateral vessels play a crucial role in the treatment of ischemic foot. PMID- 26802297 TI - Leiomyosarcoma of the Inferior Vena Cava: A Case Series and Review of the Literature. AB - BACKGROUND: Leiomyosarcoma of the inferior vena cava (IVC) is an exceedingly rare smooth muscle sarcoma. Approximately 300 cases have been described in the literature, and further research is needed to understand the disease and guide its management. Surgery remains the only potential curative measure. METHODS: A retrospective chart review of patients who underwent surgical resection of IVC leiomyosarcoma at our institution over the past 3 years was performed. The patients were identified using a prospectively maintained database. RESULTS: Three patients with leiomyosarcoma of the infrahepatic IVC underwent radical resection carried out by a team of surgical oncologists and vascular surgeons. There were 2 males (66.7%) and 1 female (33.3%). Mean age at diagnosis was 60.3 years (range 43-78). Mean tumor size was 12.2 cm (range 5.6-22). The mean operative time was 320 min (range 180-421), mean estimated blood loss was 1,300 mL (100-2,000) mL, and average length of stay 8.67 days (6-12). All patients achieved grossly negative margins (R1 or R0 resections) and are alive with a mean overall survival of 21 months (range 12-30). Patient 1 was a 60-year-old man who presented with metachronous skin leiomyosarcomas at 2 different sites. He underwent PET/CT scan that revealed an IVC mass. Resection of the middle segment of the IVC and right kidney was performed with reconstruction with polytetrafluorethylene (PTFE) graft. Patient 2 was a 78-year-old man with an incidentally found a 9-cm IVC tumor. Resection of the tumor was performed, and no reconstruction was needed since the tumor had a completely extraluminal growth pattern. Patient 3 was a 43-year-old woman who presented with abdominal pain. Her work-up showed a 15-cm IVC mass. She underwent resection of the middle segment of the IVC, right nephrectomy, and cholecystectomy with reconstruction of the IVC with PTFE graft. CONCLUSIONS: Surgical resection is the mainstay of treatment in patients with leiomyosarcoma of the IVC. A collaborative approach involving surgical oncologists and vascular surgeons ensures adequate resection with functional reconstruction to achieve the best patient outcomes. PMID- 26802296 TI - Remote Ischemic Preconditioning and Contrast-Induced Nephropathy: A Systematic Review. AB - BACKGROUND: The use of imaging is increasing in clinical practice either for diagnosis or intervention. In these aims, contrast medium (CM) is widely used. However, CM administration can induce contrast-induced nephropathy (CIN). The incidence of CIN varies from 2% to 50% depending on patient risk factors, and CIN is the third cause of renal insufficiency. To date, methods such as hyperhydration to prevent CIN have a low level of evidence. Remote ischemic preconditioning (RIPC), which has already proved its efficiency in the cardiology field, seems to be a promising technique for CIN prevention. The aim of this work was to carry out a systematic review of the literature of the randomized clinical studies on RIPC in the prevention of CIN in man. METHODS: We conducted a systematic review of randomized clinical studies on the RIPC in the prevention of CIN in man. Documentary sources were PubMed articles published until June 2015. Randomized clinical trials of RIPC in preventing CIN in human were reviewed. RESULTS: Five articles were selected for the analysis. One article studied the impact of RIPC in a population at high risk of CIN, whereas the other 4 analyzed populations at low, moderate or unknown risk of CIN. In 4 studies, except the later one, the risk of CIN was based on the Mehran score that was previously published. In the high-risk population, a decrease in the incidence of CIN was found in the RIPC group compared with the control group (12% against 40%; P = 0.002). Among the 3 other studies using the Mehran's score, one also demonstrated the interest of such a procedure in a subgroup of high-risk patients. A second one found a low incidence of CIN in the RIPC group ([5 of 47; 10%] as compared with a control group [17 of 47; 36%] P = 0.003) in patients at the low risk of CIN. In another low-risk population, a significant lower level of a biological marker (liver-type fatty acid-binding protein) that assesses a renal impairment was found in the RIPC compared with the control group. CONCLUSIONS: Only 5 studies were found in this search, which may constitute a limitation. However, RIPC appears as a promising method to prevent CIN since it is a noninvasive, low cost, easy, and safe method. More randomized controlled trials are needed to confirm these preliminary results. PMID- 26802298 TI - Creation of a Successful Transposed Antecubital Radiocephalic Arteriovenous Fistula in Patient with Known Ipsilateral Modified Radical Mastectomy, Postoperative Radiation, and Proximal Central Venous Occlusion. AB - Native arteriovenous fistula (AVF) placement in patients with ipsilateral mastectomy and radiation has been avoided because of concerns regarding central venous outflow obstruction. To our knowledge, only 3 such cases have been reported. We present a patient with bilateral mastectomies and right-sided radiation therapy presenting for vascular access in the setting of multiple failed AVF in her left upper extremity and infected-groin catheter, central catheters, and axillary loop graft. We created and superficialized a radiocephalic AVF in her right upper extremity in the setting of central vein occlusion and robust collaterals which remains patent and has been cannulated successfully. PMID- 26802299 TI - Prevalence of the Factor XIII Val34Leu Polymorphism in Korean Patients with Deep Vein Thrombosis. AB - OBJECTIVE: According to recent reports, a common polymorphism resulting in Val to Leu substitution, located 3 amino acids (Val34Leu) upstream of the thrombin cleavage site of FXIII A, has been related to a lower incidence of deep vein thrombosis (DVT). And, a different expression pattern has been shown across nations and races. However, the frequency of FXIII polymorphism expression in Koreans has not been reported in normal individuals or DVT-patient groups. DESIGN: Case-control study in Korean population. METHODS: We investigated the distribution of factor XIII Val34Leu polymorphisms in Korean patients of DVT (50 cases) and Korean healthy controls (100 cases), using real-time polymerase chain reaction for single nucleotide polymorphism genotyping. RESULTS: With regard to the frequency of the FXIII polymorphism in DVT patients and in the general control group, all 50 cases in the patient group and 100 cases in the control group were found to be Val34 homozygotes. CONCLUSIONS: The Val34Leu polymorphism of FXIII was not found in Korean people, and compared with Caucasians, a noticeably low incidence of DVT was shown. Thus, the preventive effect of the Val34 allele of FXIII on the formation of thrombi was shown. PMID- 26802300 TI - Active Ankle Movement May Prevent Deep Vein Thrombosis in Patients Undergoing Lower Limb Surgery. AB - BACKGROUND: Our aim is to investigate the effect of active ankle movement to prevent deep vein thrombosis (DVT) in patients who received lower limb surgery, and to provide a theory of evidence for rehabilitation nursing of patients after orthopedic surgery. METHODS: Between January 2012 and December 2013, a total of 174 patients were randomized as case group (n = 96) and control group (n = 78). Case group received routine nursing and active ankle movement (30 times/min, 1-7 days after surgery), while control group only received routine nursing. The symptoms and signs of DVT were in real-time observation during the experiment. Thigh and crus circumference, maximum venous outflow (MVO), maximum venous capacity (MVC), and MVO ratio (MVO ratio = MVO/MVC) in the two groups were measured 1-7 days after surgery. Six-month follow-up study was also conducted to observe the occurrence of DVT. RESULTS: Our study revealed that thigh circumference in the case group decreased compared with the control group in 5-7 days (fifth day: 39.98 +/- 3.25 vs. 41.01 +/- 3.38, P = 0.043; sixth day: 38.21 +/- 3.81 vs. 39.49 +/- 3.79, P = 0.029; seventh day: 37.13 +/- 3.15 vs. 38.76 +/- 3.31, P = 0.001), and crus circumference in the case group also decreased compared with the control group in 5-7 days (fifth day: 26.35 +/- 2.11 vs. 27.01 +/- 2.19, P = 0.045; sixth day: 25.99 +/- 2.31 vs. 26.88 +/- 3.12, P = 0.032; seventh day: 25.56 +/- 1.99 vs. 26.38 +/- 2.89, P = 0.028). MVO and MVC in the case group increased compared with the control group 7 days after surgery (MVO: 15.01 +/- 2.56 vs. 14.12 +/- 2.56, P = 0.024; MVC: 10.18 +/- 3.15 vs. 8.91 +/- 2.78, P = 0.006). Significant difference in the incidence of thrombus and DVT were found between the case group and the control group 1-7 days after surgery (thrombus: 1.0% and 7.7%, P = 0.027; DVT: 7.6% and 18.4%, P = 0.032). CONCLUSION: Our result manifested that active ankle movement can relieve the swelling of patients after lower limb surgery, and improve the MVO and MVC of patients to prevent formation of DVT after lower limb surgery. PMID- 26802301 TI - Stroke from an External Carotid: Lesion Pattern and Mechanisms. AB - Traditionally, patients with symptomatic external carotid stenosis present with neck or face pain, retinal ischemic symptoms or jaw claudication and rarely as ipsilateral cerebrovascular events. In this present case, our patient suffered a stroke from a paradoxical embolism from the external carotid, without involvement of the internal carotid artery. A plaque ulceration of the external carotid's origin was the cause of this cerebral emboli. Duplex ultrasound showed a pathologic left external carotid, with a floating thrombus in the internal carotid. The diagnostic was confirmed by a computerized tomography scan. An external carotid thromboendarterectomy was performed 6 days after symptom onset, and intraoperative findings confirmed the plaque rupture with an extensive clot in the carotid bifurcation. PMID- 26802302 TI - Promising Results of the Forearm Basilic Fistula Reveal a Worthwhile Option between Radial Cephalic and Brachial Fistula. AB - BACKGROUND: Use of the forearm basilic vein for the creation of an arteriovenous fistula has been codified as second-choice vascular access for hemodialysis in the last clinical guidelines of the Society for Vascular Surgery in 2008. Poor literature data on this technical option and on its evaluation and outcomes led us to initiate a retrospective single-center study. METHODS: We analyzed the outcomes of every arteriovenous fistula using the forearm basilic vein created in our department. It is a retrospective study in which we collected data prospectively by contacting dialysis centers, nephrologists, and patients. Primary end point was primary patency rate at 1 year. Secondary end points were secondary patency rate at 1 year, time of maturation, and Doppler flow measurement before the first puncture. RESULTS: From February 2004 to June 2014, 49 forearm basilic arteriovenous fistulas were created: 33 ulnar-basilic and 16 radial basilic arteriovenous fistulas. Initial technical success rate was 98%. Functional success rate was 60%. Primary and secondary patency rates at 1 year were respectively 21% and 48%. Median time of maturation was 81 days, and mean Doppler flow measurement was 678 mL/min. Ulnar-basilic fistulas had a statistically significant shorter time of maturation than radial basilic fistulas (P <= 0.05). CONCLUSIONS: Despite poor primary patency rate and a long time of maturation, forearm basilic arteriovenous fistula has satisfactory secondary patency rate and keeps all the advantages of a distal-located vascular access concerning complications. It is worth its second-choice place in the current algorithm of creation of vascular access for hemodialysis. PMID- 26802303 TI - Endovascular versus Open Surgery Repair of Ruptured Abdominal Aortic Aneurysms in Hemodynamically Unstable Patients: Literature Review and Meta-Analysis. AB - BACKGROUND: The better outcome achieved by endovascular aortic repair (EVAR) in ruptured abdominal aortic aneurysm (rAAA) patients might derive from the fact that patients with hemodynamic instability preferentially underwent open repair. To further evaluate the effect of EVAR for rAAAs, a meta-analysis of studies in which hemodynamic instability was similar between the 2 treatment groups was conducted. METHODS: MEDLINE, EMBASE, ISI Web of Knowledge, and the Cochrane Library were searched from January 2004 to May 2014 for randomized controlled trials (RCTs) and observational studies that compared EVAR with open surgery repair in rAAA patients. RESULTS: Three RCTs and 10 observational studies covering 1,784 patients were included. Perioperative mortality occurred in 27.3% of the patients treated with EVAR and in 38.1% of the patients who underwent open repair. Subgroup analysis revealed consistent results in favor of EVAR in single center, observational studies. Subgroup analysis and meta-regression analysis indicated that the superior effect of EVAR might be associated with more anatomically suitable patients in EVAR group. CONCLUSION: The findings from our meta-analysis support EVAR in properly selective rAAA patients. PMID- 26802304 TI - Repair of Distal Aortic Arch Aneurysms by Left Subclavian Artery Transposition with Stented Elephant Trunk Implantation. AB - BACKGROUND: Repair of distal aortic arch aneurysms remains technically challenging using conventional open surgery due to its location. Several techniques, including a conventional prosthetic graft replacement and a hybrid technique, were introduced to manipulate this lesion. We retrospectively reviewed our experience with left subclavian artery (LSCA) transposition with stented elephant trunk implantation for repair of distal aortic arch aneurysms. METHODS: From May 2009 to December 2014, 9 men (mean age 55 +/- 16 years) with distal aortic arch aneurysms underwent LSCA transposition with stented elephant trunk implantation under hypothermic cardiopulmonary bypass with antegrade selective cerebral perfusion via a median sternotomy. One case had a history of endovascular abdominal aortic repair. RESULTS: There was no in-hospital death. The mean time of mechanical ventilation and intensive care unit stay was 22 +/- 9 and 53 +/- 17 hr, respectively. No severe complications occurred in this group. All patients survived and were discharged. No patient died during the follow-up period. Postoperative computed tomography revealed good patency of the anastomotic site between the LSCA and the left common carotid artery. CONCLUSIONS: Satisfactory surgical results and follow-up outcomes were achieved by simultaneous repair of proximal aortic lesions and complete seal of the lesion involving the distal aortic arch and proximal descending aorta using LSCA transposition with implantation of a stented elephant trunk. Encouraging outcomes favor this technique for distal aortic arch aneurysm. PMID- 26802305 TI - Two Aortic Ruptures in Two Months-Role of Cross-Clamp-Associated Late Injury. AB - BACKGROUND: Aortic cross-clamping may lead to iatrogenic tissue damage resulting in immediate or later aortic dissection or rupture. METHODS: We report on a patient with an acute type B aortic dissection with mega-aortic syndrome whose aorta ruptured twice within 2 months. RESULTS: The second aortic rupture occurred at the level of prior cross clamping. The pressure along the clamp jaws is distributed unequally. According to the law of the lever, the aortic area near the hinge is under more stress than the aortic area distal to the hinge. Unequal pressure distribution may injure the aorta. CONCLUSIONS: There is a need to evaluate pressure distribution along the various currently available aortic clamp jaws and to develop the perfect aortic clamp providing equal pressure distribution designed especially to clamp large aortas or those of patients with connective tissue disorders. PMID- 26802306 TI - Thoracic Endovascular Aortic Repair for Traumatic Thoracic Aortic Injury: A Single-Center Initial Experience. AB - BACKGROUND: Several publications have documented the technical feasibility and efficacy of stent grafting for aortic injuries. We report short- and mid-term results of thoracic endovascular repair with covered stent grafts for type B blunt thoracic aortic injury. METHODS: We performed a retrospective review of patients who had sustained blunt thoracic aortic injuries. From January 2010 to March 2014, 13 patients (12 men and 1 woman) were admitted and treated in our department for type B thoracic aortic injury. The patients' ages ranged from 19 to 62 years. Traffic accidents were responsible for 10 of the 13 blunt thoracic aortic injuries, and the remainder was caused by blunt trauma from falls. Medical records were examined to identify the clinical outcomes of the procedures, and follow-up computed tomography scans were reviewed to document the efficacy of thoracic endovascular aortic repair. RESULTS: Endovascular stent grafting was technically successful in all cases, and no paraplegia or stroke-like events were reported. No major cardiac, neurologic, or peripheral vascular complications were observed during early or late follow-up. None of the patients died from procedure related complications. CONCLUSIONS: Our single-center experience demonstrates the feasibility of performing endovascular repair for type B blunt aortic injury. As experience with endovascular surgery accumulates, this method of treatment promises to become the first-choice option for repairing this type of aortic injury, with less associated morbidity and mortality relative to conventional surgical repair. PMID- 26802307 TI - Spinal Cord Stimulation Therapy for the Treatment of Concomitant Phantom Limb Pain and Critical Limb Ischemia. AB - Phantom limb pain (PLP) is a chronic condition experienced by about 80% of patients who have undergone amputation. In most patients, both the frequency and the intensity of pain attacks diminish with time, but severe pain persists in about 5-10%. Probably, factors in both the peripheral and central nervous system play a role in the occurrence and persistence of pain in the amputated lower limb. The classical treatment of PLP can be divided into pharmacologic, surgical, anesthetic, and psychological modalities. Spinal cord stimulation (SCS) does not represent a new method of treatment for this condition. However, the concomitant treatment of PLP and critical lower limb ischemia by using SCS therapy has not yet been described in the current literature. The aim of the present article is to highlight the possibility of apply SCS for the simultaneous treatment of PLP and critical lower limb ischemia on the contralateral lower limb after failure of medical therapy in a group of 3 patients, obtaining pain relief in both lower limbs, delaying an endovascular or surgical revascularization. After SCS implantation and test stimulation, the pain was reduced by 50% on both the right and the left side in all our patients. The main indications for permanent SCS therapy after 1 week of test stimulation were represented by transcutaneous oxygen (TcPO2) increase >75%, decrease of opioids analgesics use of at least 50% and a pain maintained to within 20-30/100 mm on visual analog scale. PMID- 26802308 TI - Abdominal Aortic Thrombosis in a Healthy Neonate. AB - Abdominal aortic thrombosis is a rare entity in neonates and has mostly been associated with umbilical artery or cardiac catheterization. We present a complicated case of an otherwise healthy neonate who developed thrombosis of abdominal aorta with renal failure. Therapy with intravenous heparin was unsuccessful, and thrombolysis was contraindicated because of disseminated intravascular coagulation so we decided to perform open thrombectomy using the left retroperitoneal approach. The following day, thrombosis recurred in the same extent and despite high risk of bleeding Alteplase was eventually given, which resulted in recanalization of the aorta 6 hours later. Renal function recovered, dialysis was discontinued, and further course was uneventful. The treatment of abdominal aortic thrombosis in neonates should be considered on a case-by-case basis because the available data on the condition are limited to case report and series. If open thrombectomy is performed, retroperitoneal approach should be preferred because it allows for easy institution of peritoneal dialysis should the need arise. PMID- 26802309 TI - Resveratrol and the mitochondria: From triggering the intrinsic apoptotic pathway to inducing mitochondrial biogenesis, a mechanistic view. AB - BACKGROUND: Mitochondria, the power plants of the cell, are known as a cross-road of different cellular signaling pathways. These cytoplasmic double-membraned organelles play a pivotal role in energy metabolism and regulate calcium flux in the cells. It is well known that mitochondrial dysfunction is associated with different diseases such as neurodegeneration and cancer. A growing body of literature has shown that polyphenolic compounds exert direct effects on mitochondrial ultra-structure and function. Resveratrol is known as one of the most common bioactive constituents of red wine, which improves mitochondrial functions under in vitro and in vivo conditions. SCOPE OF REVIEW: This paper aims to review the molecular pathways underlying the beneficial effects of resveratrol on mitochondrial structure and functions. In addition, we discuss the chemistry and main sources of resveratrol. MAJOR CONCLUSIONS: Resveratrol represents the promising effects on mitochondria in different experimental models. However, there are several reports on the detrimental effects elicited by resveratrol on mitochondria. GENERAL SIGNIFICANCE: An understanding of the chemistry and source of resveratrol, its bioavailability and the promising effects on mitochondria brings a new hope to therapy of mitochondrial dysfunction-related diseases. PMID- 26802310 TI - A novel chemically modified analogue of xenin-25 exhibits improved glucose lowering and insulin-releasing properties. AB - BACKGROUND: Xenin-25 is a K-cell derived gut peptide with insulin-releasing activity which is rapidly degraded following release into the circulation. We hypothesized that substitution of all naturally-occurring Lys and Arg residues with Gln would lead to prolonged enzyme resistance and enhanced biological efficacy. METHODS: Peptide stability was assessed using murine plasma, in vitro insulin-releasing actions evaluated in BRIN-BD11 cells and acute glucose-lowering and insulin-releasing actions examined in high fat fed mice. For sub-chronic studies, a range of metabolic parameters and pancreatic histology were assessed in high fat fed mice which had received saline vehicle or xenin-25(gln) twice daily for 21 days. RESULTS: In contrast to native xenin-25, xenin-25(gln) was resistant to plasma-mediated degradation and significantly stimulated insulin secretion in BRIN-BD11 cells. Acute administration of xenin-25(gln) in high fat fed mice significantly reduced blood glucose and increased plasma insulin concentrations. Twice-daily administration of xenin-25(gln) in high fat fed mice did not affect food intake, body weight or circulating insulin concentrations but significantly decreased blood glucose from day 9 onwards. Furthermore, glucose tolerance, glucose-mediated insulin secretion, insulin sensitivity and GIP stimulated insulin-release were significantly enhanced in xenin-25(gln)-treated mice. Pancreatic immunohistochemistry revealed decreased alpha cell area with increased beta cell area and beta-to-alpha cell ratio in xenin-25(gln)-treated mice. In addition, xenin-25(gln) exerted similar beneficial actions in ob/ob mice as demonstrated by reduced blood glucose, superior glycaemic response and glucose mediated insulin release. CONCLUSIONS: Xenin-25(gln) is resistant to plasma mediated degradation and exerts sustained and beneficial metabolic actions in high fat fed and ob/ob mice. GENERAL SIGNIFICANCE: Glutamine (gln)-modified analogues of xenin may represent an attractive therapeutic approach for type 2 diabetes. PMID- 26802311 TI - Impact of donor binding on polymerization catalyzed by KfoC by regulating the affinity of enzyme for acceptor. AB - BACKGROUND: Currently marketed chondroitin sulfate isolated from animal sources and structurally quite heterogeneous. Synthesis of structurally defined chondroitin sulfate is highly desired. The capsular polysaccharide from Escherichia coli strain K4 is similar to chondroitin, and its biosynthesis requires a chondroitin polymerase (KfoC). The essential step toward de novo enzymatic synthesis of chondroitin sulfate, synthesis of chondroitin, could be achieved by employing this enzyme. METHODS: Structurally defined acceptors and donor-sugars were prepared by chemoenzymatic approaches. In addition, surface plasmon resonance was employed to determine the binding affinities of individual substrates and donor-acceptor pairs for KfoC. RESULTS: KfoC has broad donor substrate specificity and acceptor promiscuity, making it an attractive tool enzyme for use in structurally-defined chimeric glycosaminoglycan oligosaccharide synthesis in vitro. In addition, the binding of donor substrate molecules regulated the affinity of KfoC for acceptors, then influenced the glycosyl transferase reaction catalyzed by this chondroitin polymerase. CONCLUSION AND GENERAL SIGNIFICANCE: These results assist in the development of enzymatic synthesis approaches toward chimeric glycosaminoglycan oligosaccharides and designing future strategies for directed evolution of KfoC in order to create mutants toward user-defined goals. PMID- 26802313 TI - F-actin remodeling defects as revealed in primary immunodeficiency disorders. AB - Primary immunodeficiencies (PIDs) are a heterogeneous group of immune-related diseases. PIDs develop due to defects in gene-products that have consequences to immune cell function. A number of PID-proteins is involved in the remodeling of filamentous actin (f-actin) to support the generation of a contact zone between the antigen-specific T cell and antigen presenting cell (APC): the immunological synapse (IS). IS formation is the first step towards T-cell activation and essential for clonal expansion and acquisition of effector function. We here evaluated PIDs in which aberrant f-actin-driven IS formation may contribute to the PID disease phenotypes as seen in patients. We review examples of such contributions to PID phenotypes from literature, and highlight cases in which PID proteins were evaluated for a role in f-actin polymerization and IS formation. We conclude with the proposition that patient groups might benefit from stratifying them in distinct functional groups in regard to their f-actin remodeling phenotypes in lymphocytes. PMID- 26802312 TI - Aminoglycoside binding and catalysis specificity of aminoglycoside 2" phosphotransferase IVa: A thermodynamic, structural and kinetic study. AB - BACKGROUND: Aminoglycoside O-phosphotransferases make up a large class of bacterial enzymes that is widely distributed among pathogens and confer a high resistance to several clinically used aminoglycoside antibiotics. Aminoglycoside 2"-phosphotransferase IVa, APH(2")-IVa, is an important member of this class, but there is little information on the thermodynamics of aminoglycoside binding and on the nature of its rate-limiting step. METHODS: We used isothermal titration calorimetry, electrostatic potential calculations, molecular dynamics simulations and X-ray crystallography to study the interactions between the enzyme and different aminoglycosides. We determined the rate-limiting step of the reaction by the means of transient kinetic measurements. RESULTS: For the first time, Kd values were determined directly for APH(2")-IVa and different aminoglycosides. The affinity of the enzyme seems to anti-correlate with the molecular weight of the ligand, suggesting a limited degree of freedom in the binding site. The main interactions are electrostatic bonds between the positively charged amino groups of aminoglycosides and Glu or Asp residues of APH. In spite of the significantly different ratio Kd/Km, there is no large difference in the transient kinetics obtained with the different aminoglycosides. We show that a product release step is rate-limiting for the overall reaction. CONCLUSIONS: APH(2")-IVa has a higher affinity for aminoglycosides carrying an amino group in 2' and 6', but tighter bindings do not correlate with higher catalytic efficiencies. As with APH(3') IIIa, an intermediate containing product is preponderant during the steady state. GENERAL SIGNIFICANCE: This intermediate may constitute a good target for future drug design. PMID- 26802314 TI - Molecular and functional characterization of Kv 7 channels in penile arteries and corpus cavernosum of healthy and metabolic syndrome rats. AB - BACKGROUND AND PURPOSE: KCNQ-encoded voltage-dependent potassium channels (Kv 7) are involved in the regulation of vascular tone. In this study we evaluated the influence of Kv 7 channel activation on smooth muscle relaxation in rat penile arteries and corpus cavernosum from normal and spontaneously hypertensive, heart failure-prone (SHHF) rats - a rat model of human metabolic syndrome. EXPERIMENTAL APPROACH: Quantitative PCR and immunohistochemistry were used to determine the expression of KCNQ isoforms in penile tissue. Isometric tension was measured in intracavernous arterial rings and corpus cavernosum strips isolated from normal and SHHF rats. KEY RESULTS: Transcripts for KCNQ3, KCNQ4 and KCNQ5 were detected in penile arteries and corpus cavernosum. KCNQ1 was only found in corpus cavernosum. Immunofluorescence signals to Kv 7.4 and Kv 7.5 were found in penile arteries, penile veins and corpus cavernosum. The Kv 7.2-7.5 activators, ML213 and BMS204352, relaxed pre-contracted penile arteries and corpus cavernosum independently of nitric oxide synthase or endothelium-derived hyperpolarization. Relaxations to sildenafil, a PDE5 inhibitor, and sodium nitroprusside (SNP), an nitric oxide donor, were reduced by blocking Kv 7 channels with linopirdine in penile arteries and corpus cavernosum. In SHHF rat penile arteries and corpus cavernosum, relaxations to ML213 and BMS204352 were attenuated, and the blocking effect of linopirdine on sildenafil-induced and SNP-induced relaxations reduced. KCNQ3, KCNQ4 and KCNQ5 were down-regulated, and KCNQ1 was up-regulated in corpus cavernosum from SHHF rats. KCNQ1-5 transcripts remained unchanged in penile arteries from SHHF rats. CONCLUSIONS AND IMPLICATIONS: These data suggest that Kv 7 channels play a role in erectile function and contribute to the pathophysiology of erectile dysfunction, an early indicator of cardiovascular disease. PMID- 26802315 TI - Rapid onset of treatment effects on psychosis, depression, and mania in patients with acute exacerbation of schizoaffective disorder following treatment with oral extended-release paliperidone. AB - BACKGROUND: Patients with schizoaffective disorder (SCA) experience complicated interplays of psychotic, depressive, and manic symptoms. Paliperidone extended release (pali ER) tablets have been shown to be efficacious in these patients, but treatment response has not been studied relative to the onset of effects for these symptom domains. METHODS: In a pooled analysis of data from two 6-week, randomized, placebo-controlled studies, the onset of treatment effects with oral pali ER was evaluated by symptom domain (psychosis, depression, mania) in patients with an acute SCA exacerbation. Subjects were categorized as having prominent psychotic (Positive and Negative Syndrome Scale score >70), depressive (Hamilton Rating Scale for Depression-21 score >=16), or manic (Young Mania Rating Scale score >=16) symptoms at baseline. RESULTS: Of the 614 patients in these analyses, 597 (97.2%), 411 (66.9%), and 488 (79.5%) had prominent psychotic, depressive, and manic symptoms at baseline, respectively. Pali ER treatment was associated with rapid and significant improvement of all three symptom domains versus placebo within 1 week of initiation, regardless of whether treatment was given as monotherapy or in combination with mood stabilizers and/or antidepressants. Adverse events were similar to those reported in the original published studies. LIMITATIONS: This post hoc analysis of two phase 3 trials requires confirmation in prospective studies. CONCLUSION: This pooled analysis suggests that treatment with pali ER is associated with rapid control of psychotic, depressive, and manic symptoms in patients with SCA. Its findings support the benefit of pali ER as a primary treatment for the management of SCA. PMID- 26802316 TI - Perinatal Major Depression Biomarkers: A systematic review. AB - Postpartum depression, now termed perinatal depression by the DSM-5, is a clinically relevant disorder reaching 15% of incidence. Although it is quite frequent and associated with high social dysfunction, only recently its underpinning biological pathways have been explored, while multiple and concomitant risk factors have been identified (e.g. psychosocial stress). Peripartum depression usually has its onset during the third trimester of pregnancy or in the postpartum, being one of the most common medical complications in new mothers. Purpose of the present review is to summarize the state of art of biological biomarkers involved in the pathogenesis of perinatal depression, in view of the fact that suboptimal prenatal milieu can induce permanent damage in subsequent offspring life and have a negative impact on mother-child relationship. Furthermore, parents' biological changes due to medical/psychiatric disorders or stress exposure could influence offspring life: a concept known as 'intergenerational transmission', acting by variations into gametes and the gestational uterine environment. Given the evidence that perinatal mental disorders involve risks for the mother and offspring, the search for reliable biomarkers in high-risk mothers actually represents a medical priority to prevent perinatal depression. PMID- 26802317 TI - Young people with Type 1 diabetes of non-white ethnicity and lower socio-economic status have poorer glycaemic control in England and Wales. AB - BACKGROUND: The impact of ethnicity and socio-economic status (SES) on glycaemic control during childhood Type 1 diabetes is poorly understood in England and Wales. METHODS: We studied 18 478 children with Type 1 diabetes (< 19 years) attending diabetes clinics and included in the 2012-2013 National Paediatric Diabetes Audit. Self-identified ethnicity was categorized as white, Asian, black, mixed, other and 'not-stated' (did not to divulge ethnicity). A small area measure of SES was estimated from the Index of Multiple Deprivation. Multiple linear regression was used to assess associations between ethnicity, SES and glycaemic control (mean HbA1c levels) accounting for age, gender and diabetes duration. The impact of insulin pump use on the ethnicity/SES-HbA1c associations was tested in 13 962 children. RESULTS: All children from minority ethnic groups had higher mean HbA1c compared with white children, with largest differences observed in black and mixed ethnicities [8 mmol/mol (2.9%), 95% CI 5-11 and 7 mmol/mol (2.8%), 95% CI 5-9, respectively]. Lower SES was associated with higher mean HbA1c with a dose effect. The lowest SES group had a mean HbA1c that was 7 mmol/mol (2.8%) (95% CI 6-8) higher compared with the highest SES group, adjusted for ethnicity. Estimates for ethnicity were attenuated, but significant on adjustment for SES. Fewer non-white (white 20.3 vs. black 5.5%) and deprived (least deprived 21.1 vs. most deprived 13.2%) children were on insulin pump therapy. Ethnicity and SES remained significant predictors of HbA1c after accounting for insulin pump use. CONCLUSION: The association between ethnicity and glycaemic control persists after adjustment for deprivation and pump use. An alternative approach to intensive insulin therapy might benefit these vulnerable children. PMID- 26802318 TI - Targeting prostate cancer cells en route to dissemination. PMID- 26802319 TI - Identification of neonatal haemolysis: an approach to predischarge management of neonatal hyperbilirubinemia. AB - AIM: Relative contributions of increased production [by end-tidal carbon monoxide concentrations (ETCOc)] and decreased elimination of bilirubin to predischarge hour-specific total bilirubin (TB) levels were assessed in healthy late-preterm and term newborns. Secondly, we report predischarge ETCOc ranges to guide clinical management of hyperbilirubinemia. METHODS: TB and ETCOc (<=3 timepoints) determinations of newborns aged between six hours and <6 days (n = 79) were stratified by postnatal age epochs. Hyperbilirubinemia risk was assessed by plotting TB values as a function of ETCOc. RESULTS: Stratifications of ETCOc (in ppm, mean, median and interquartile ranges) by postnatal age epochs (0-24, 24-48 and 48-72) were as follows: 2.0, 1.9, 1.8-2.2 (n = 11); 1.6, 1.5, 1.1-2.0 (n = 58); and 2.0, 1.8, 1.6-2.3 (n = 9), respectively. Infants with ETCOc >= 2.5 were at high risk, between 1.5 and 2.5 at moderate risk and <=1.5 were at low risk. Risk due to haemolysis alone was not independent (p < 0.01). For infants with TB >75th percentile (n = 31), 23% had ETCO <=1.5, and 77% had ETCOc > 1.5 (p < 0.00003). CONCLUSION: Near-simultaneous ETCOc and TB measurements in infants with TB >75th percentile accurately identify haemolytic hyperbilirubinemia. PMID- 26802320 TI - Advances in Experimental Neuropathology: New Methods and Insights. AB - This Editorial introduces this month's special Neuropathology Theme Issue, a series of Reviews on advances in our understanding of rare human hereditary neuropathies, peripheral nervous system tumors, and common degenerative diseases. PMID- 26802322 TI - Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model. AB - The canine hematopoietic stem cell transplantation (HSCT) model has become accepted in recent decades as a good preclinical model for the development of new transplantation strategies. Information on factors associated with outcome after allogeneic HSCT are a prerequisite for designing new risk-adapted transplantation protocols. Here we report a retrospective analysis aimed at identifying risk factors for allograft rejection in the canine HSCT model. A total of 75 dog leukocyte antigen-identical sibling HSCTs were performed since 2003 on 10 different protocols. Conditioning consisted of total body irradiation at 1.0 Gy (n = 20), 2.0 Gy (n = 40), or 4.5 Gy (n = 15). Bone marrow was infused either intravenously (n = 54) or intraosseously (n = 21). Cyclosporin A alone or different combinations of cyclosporine A, mycophenolate mofetil, and everolimus were used for immunosuppression. A median cell dose of 3.5 (range, 1.0 to 11.8) total nucleated cells (TNCs)/kg was infused. Cox analyses were used to assess the influence of age, weight, radiation dose, donor/recipient sex, type of immunosuppression, and cell dose (TNCs, CD34(+) cells) on allograft rejection. Initial engraftment occurred in all dogs. Forty-two dogs (56%) experienced graft rejection at median of 11 weeks (range, 6 to 56 weeks) after HSCT. Univariate analyses revealed radiation dose, type of immunosuppression, TNC dose, recipient weight, and recipient age as factors influencing long-term engraftment. In multivariate analysis, low radiation dose (P < .001) and low TNC cell count (P = .044) were identified as significant independent risk factors for graft rejection. Peripheral blood mononuclear cell chimerism >=30% (P = .008) and granulocyte chimerism >=70% (P = .023) at 4 weeks after HSCT were independent predictors of stable engraftment. In summary, these data indicate that even in low-dose total body irradiation-based regimens, the irradiation dose is important for engraftment. The level of blood chimerism at 4 weeks post-HSCT was predictive of long-term engraftment in the canine HSCT model. PMID- 26802324 TI - Bronchiolitis Obliterans: Pleading for a Pragmatic Approach. PMID- 26802326 TI - Beef Tea, Vitality, Creatinine, and the Estimated GFR. PMID- 26802325 TI - Crumbs 2 prevents cortical abnormalities in mouse dorsal telencephalon. AB - The formation of a functionally integrated nervous system is dependent on a highly organized sequence of events that includes timely division and differentiation of progenitors. Several apical polarity proteins have been shown to play crucial roles during neurogenesis, however, the role of Crumbs 2 (CRB2) in cortical development has not previously been reported. Here, we show that conditional ablation of Crb2 in the murine dorsal telencephalon leads to defects in the maintenance of the apical complex. Furthermore, within the mutant dorsal telencephalon there is premature expression of differentiation proteins. We examined the physiological function of Crb2 on wild type genetic background as well as on background lacking Crb1. Telencephalon lacking CRB2 resulted in reduced levels of PALS1 and CRB3 from the apical complex, an increased number of mitotic cells and expanded neuronal domain. These defects are transient and therefore only result in rather mild cortical abnormalities. We show that CRB2 is required for maintenance of the apical polarity complex during development of the cortex and regulation of cell division, and that loss of CRB2 results in cortical abnormalities. PMID- 26802327 TI - Mesoamerican Nephropathy: Do Novel Biomarkers of Kidney Damage Have a Role to Play? PMID- 26802323 TI - Late Effects Surveillance Recommendations among Survivors of Childhood Hematopoietic Cell Transplantation: A Children's Oncology Group Report. AB - Hematopoietic cell transplantation (HCT) is an important curative treatment for children with high-risk hematologic malignancies, solid tumors, and, increasingly, nonmalignant diseases. Given improvements in care, there are a growing number of long-term survivors of pediatric HCT. Compared with childhood cancer survivors who did not undergo transplantation, HCT survivors have a substantially increased burden of serious chronic conditions and impairments involving virtually every organ system and overall quality of life. This likely reflects the joint contributions of pretransplantation treatment exposures and organ dysfunction, the transplantation conditioning regimen, and any post transplantation graft-versus-host disease (GVHD). In response, the Children's Oncology Group (COG) has created long-term follow-up guidelines (www.survivorshipguidelines.org) for survivors of childhood, adolescent, and young adult cancer, including those who were treated with HCT. Guideline task forces, consisting of HCT specialists, other pediatric oncologists, radiation oncologists, organ-specific subspecialists, nurses, social workers, other health care professionals, and patient advocates systematically reviewed the literature with regards to late effects after childhood cancer and HCT since 2002, with the most recent review completed in 2013. For the most recent review cycle, over 800 articles from the medical literature relevant to childhood cancer and HCT survivorship were reviewed, including 586 original research articles. Provided herein is an organ system-based overview that emphasizes the most relevant COG recommendations (with accompanying evidence grade) for the long-term follow-up care of childhood HCT survivors (regardless of current age) based on a rigorous review of the available evidence. These recommendations cover both autologous and allogeneic HCT survivors, those who underwent transplantation for nonmalignant diseases, and those with a history of chronic GVHD. PMID- 26802328 TI - Vascular Access, Mortality, and Home Hemodialysis: Back to the Future. PMID- 26802329 TI - Optimal Plasma and Dialysate Magnesium Concentrations in Hemodialysis Patients: The Unsettled Issues. PMID- 26802330 TI - In Reply to 'Optimal Plasma and Dialysate Magnesium Concentrations in Hemodialysis Patients: The Unsettled Issues'. PMID- 26802331 TI - In Reply to 'Serum Fractalkines and Cardiovascular Outcomes in the CRIC Study Cohort'. PMID- 26802332 TI - Serum Fractalkines and Cardiovascular Outcomes in the CRIC Study Cohort. PMID- 26802333 TI - Quiz Page February 2016: Acute Kidney Injury in a Patient With Granulomatosis With Polyangiitis Receiving Maintenance Immunosuppressive Therapy. PMID- 26802334 TI - AJKD Atlas of Renal Pathology: Light and Heavy Chain Deposition Disease. PMID- 26802335 TI - AJKD Atlas of Renal Pathology: Cryoglobulinemic Glomerulonephritis. PMID- 26802336 TI - AJKD Atlas of Renal Pathology: Light Chain Proximal Tubulopathy. PMID- 26802337 TI - Characterization of leaf-level particulate matter for an industrial city using electron microscopy and X-ray microanalysis. AB - This study reports application of monitoring and characterization protocol for particulate matter (PM) deposited on tree leaves, using Quercus ilex as a case study species. The study area is located in the industrial city of Terni in central Italy, with high PM concentrations. Four trees were selected as representative of distinct pollution environments based on their proximity to a steel factory and a street. Wash off from leaves onto cellulose filters were characterized using scanning electron microscopy and energy dispersive X-ray spectroscopy, inferring the associations between particle sizes, chemical composition, and sampling location. Modeling of particle size distributions showed a tri-modal fingerprint, with the three modes centered at 0.6 (factory related), 1.2 (urban background), and 2.6MUm (traffic related). Chemical detection identified 23 elements abundant in the PM samples. Principal component analysis recognized iron and copper as source-specific PM markers, attributed mainly to industrial and heavy traffic pollution respectively. Upscaling these results on leaf area basis provided a useful indicator for strategic evaluation of harmful PM pollutants using tree leaves. PMID- 26802339 TI - Airborne castanea pollen forecasting model for ecological and allergological implementation. AB - Castanea sativa Miller belongs to the natural vegetation of many European deciduous forests prompting impacts in the forestry, ecology, allergological and chestnut food industry fields. The study of the Castanea flowering represents an important tool for evaluating the ecological conservation of North-Western Spain woodland and the possible changes in the chestnut distribution due to recent climatic change. The Castanea pollen production and dispersal capacity may cause hypersensitivity reactions in the sensitive human population due to the relationship between patients with chestnut pollen allergy and a potential cross reactivity risk with other pollens or plant foods. In addition to Castanea pollen's importance as a pollinosis agent, its study is also essential in North Western Spain due to the economic impact of the industry around the chestnut tree cultivation and its beekeeping interest. The aim of this research is to develop an Artificial Neural Networks for predict the Castanea pollen concentration in the atmosphere of the North-West Spain area by means a 20years data set. It was detected an increasing trend of the total annual Castanea pollen concentrations in the atmosphere during the study period. The Artificial Neural Networks (ANNs) implemented in this study show a great ability to predict Castanea pollen concentration one, two and three days ahead. The model to predict the Castanea pollen concentration one day ahead shows a high linear correlation coefficient of 0.784 (individual ANN) and 0.738 (multiple ANN). The results obtained improved those obtained by the classical methodology used to predict the airborne pollen concentrations such as time series analysis or other models based on the correlation of pollen levels with meteorological variables. PMID- 26802338 TI - Transport and retention of bacteria and viruses in biochar-amended sand. AB - The transport and retention of Escherichia coli and bacteriophages (PRD1, MS2 and FX174), as surrogates for human pathogenic bacteria and viruses, respectively, were studied in the sand that was amended with several types of biochar produced from various feedstocks. Batch and column studies were conducted to distinguish between the role of attachment and straining in microbe retention during transport. Batch experiments conducted at various solution chemistries showed negligible attachment of viruses and bacteria to biochar before or after chemical activation. At any given solution ionic strength, the attachment of viruses to sand was significantly higher than that of biochar, whereas bacteria showed no attachment to either sand or biochar. Consistent with batch results, biochar addition (10% w/w) to sand reduced virus retention in the column experiments, suggesting a potential negative impact of biochar application to soil on virus removal. In contrast, the retention of bacteria was enhanced in biochar-amended sand columns. However, elimination of the fine fraction (<60MUm) of biochar particles in biochar-amended sand columns significantly reduced bacteria retention. Results from batch and column experiments suggest that land application of biochar may only play a role in microbe retention via straining, by alteration of pore size distribution, and not via attachment. Consequently, the particle size distribution of biochar and sediments is a more important factor than type of biochar in determining whether land application of biochar enhances or diminishes microbial retention. PMID- 26802340 TI - Predicting pesticide removal efficacy of vegetated filter strips: A meta regression analysis. AB - Vegetated Filter Strips (VFS's) are widely used for alleviating agricultural pesticide loadings to surface water bodies. However, effective tools are lacking to quantify the performance of VFS's in reducing off-site pesticide transport. In this study, we applied meta-regression to develop a model for predicting VFS pesticide retention efficiency based on hydrologic responses of VFS's, incoming pollutant characteristics and the interaction within and between these two factor groups (R(2)=0.83). In cross-validation analysis, our model (Q(2)=0.81) outperformed the existing pesticide retention module of VFSMOD (Q(2)=0.72) by explicitly accounting for interaction effect and the categorical effect of pesticide adsorption properties. Based on the 181 data points studied, infiltration had a leading, positive influence on pesticide retention, followed by sedimentation and interaction between the two. Interaction between infiltration and pesticide adsorption properties was also prominent, as the influence of infiltration was significantly lower for strongly adsorbed pesticides. In addition, the clay content of incoming sediment was negatively associated with pesticide retention. Our model is not only valuable in predicting VFS performance, but also provides a quantitative characterization of the interacting VFS processes, thereby facilitating a deeper understanding of the underlying mechanisms. PMID- 26802341 TI - An assay for determining minimal concentrations of antibiotics that drive horizontal transfer of resistance. AB - Ability to understand the factors driving horizontal transfer of antibiotic resistance from unknown, harmless bacteria to pathogens is crucial in order to tackle the growing resistance problem. However, current methods to measure effects of stressors on horizontal gene transfer have limitations and often fall short, as the estimated endpoints can be a mix of both the number of transfer events and clonal growth of transconjugants. Our aim was therefore to achieve a proper strategy for assessing the minimal concentration of a stressor (exemplified by tetracycline) that drives horizontal transfer of antibiotic resistance from a complex community to a model pathogen. Conditions were optimized to improve a culture-based approach using the bacterial community of treated sewage effluent as donor, and fluorescent, traceable Escherichia coli as recipient. Reduced level of background resistance, differentiation of isolates as well as decreased risk for measuring effects of selection were achieved through the use of chromogenic medium, optimization of conjugation time as well as applying a different antibiotic for isolation of transconjugants than the one tested for its ability to drive transfer. Using this assay, we showed that a very low concentration of tetracycline, 10MUg/L i.e. 150 times below the minimal inhibitory concentration of the recipient, promoted horizontal transfer of multiple antibiotic-resistance determinants. Higher concentrations favoured selection of a tetracycline-resistance phenotype along with a decline in the number of detectable transfer events. The described method can be used to evaluate different environmental conditions and factors that trigger horizontal dissemination of mobile resistance elements, eventually resulting in the formation of drug-resistant pathogens. PMID- 26802342 TI - Phytotoxicity of chiral herbicide bromacil: Enantioselectivity of photosynthesis in Arabidopsis thaliana. AB - With the wide application of chiral herbicides and the frequent detection of photosystem II (PSII) herbicides, it is of great importance to assess the direct effects of PSII herbicides on photosynthesis in an enantiomeric level. In the present study, the enantioselective phytotoxicity of bromacil (BRO), typical photosynthesis inhibition herbicide, on Arabidopsis thaliana was investigated. The results showed that S-BRO exhibited a greater inhibition of electron transmission in photosystem I (PSI) of A. thaliana than R-BRO by inhibiting the transcription of fnr 1. S-BRO also changed the chlorophyll fluorescence parameters Y (II), Y (NO), and Y (NPQ) to a greater extent than R-Bro. Transcription of genes psbO2, Lhcb3 and Lhcb6 was down-regulated in an enantioselective rhythm and S-BRO caused more serious influence, indicating that S-BRO did worse damage to the photosystem II (PSII) of A. thaliana than R-BRO. This study suggested that S-BRO disturbed the photosynthesis of plants to a larger extent than R-BRO and provided a new sight to evaluate the phytotoxicity of chiral herbicides. PMID- 26802343 TI - Occurrence of pharmaceuticals and cocaine in a Brazilian coastal zone. AB - The present study determined environmental concentrations of pharmaceuticals, cocaine, and the main human metabolite of cocaine in seawater sampled from a subtropical coastal zone (Santos, Brazil). The Santos Bay is located in a metropolitan region and receives over 7367m(3) of wastewater per day. Five sample points under strong influence of the submarine sewage outfall were chosen. Through quantitative analysis by LC-MS/MS, 33 compounds were investigated. Seven pharmaceuticals (atenolol, acetaminophen, caffeine, losartan, valsartan, diclofenac, and ibuprofen), an illicit drug (cocaine), and its main human metabolite (benzoylecgonine) were detected at least once in seawater sampled from Santos Bay at concentrations that ranged from ng.L(-1) to MUg.L(-1). In light of the possibility of bioaccumulation and harmful effects, the high concentrations of pharmaceuticals and cocaine found in this marine subtropical ecosystem are of environmental concern. PMID- 26802344 TI - Mechanism-specific and whole-organism ecotoxicity of mono-rhamnolipids. AB - Biosurfactants like rhamnolipids are promising alternatives to chemical surfactants in a range of applications. A wider use requires an analysis of their environmental fate and their ecotoxicological potential. In the present study mono-rhamnolipids produced by a recombinant Pseudomonas putida strain were analyzed using the Green Toxicology concept for acute and mechanism-specific toxicity in an ecotoxicological test battery. Acute toxicity tests with the invertebrate Daphnia magna and with zebrafish embryos (Danio rerio) were performed. In addition, microbial and fungicidal effectiveness was investigated. Mutagenicity of the sample was tested by means of the Ames fluctuation assay. A selected mono-rhamnolipid was used for model simulations regarding mutagenicity and estrogenic activity. Our results indicate that mono-rhamnolipids cause acute toxicity to daphnids and zebrafish embryos comparable to or even lower than chemical surfactants. Rhamnolipids showed very low toxicity to the germination of Aspergillus niger spores and the growth of Candida albicans. No frameshift mutation or base substitutions were observed using the Ames fluctuation assay with the two tester strains TA98 and TA100. This result was confirmed by model simulations. Likewise it was computed that rhamnolipids have no estrogenic potential. In conclusion, mono-rhamnolipids are an environmental friendly alternative to chemical surfactants as the ecotoxicological potential is low. PMID- 26802345 TI - An empirical investigation of climate and land-use effects on water quantity and quality in two urbanising catchments in the southern United Kingdom. AB - Using historical data of climate, land-use, hydrology and water quality from four catchments located in the south of England, this study identifies the impact of climate and land-use change on selected water quantity and water quality indicators. The study utilises a paired catchment approach, with two catchments that have experienced a high degree of urbanisation over the past five decades and two nearby, hydrologically similar, but undeveloped catchments. Multivariate regression models were used to assess the influence of rainfall and urbanisation on runoff (annual and seasonal), dissolved oxygen levels and temperature. Results indicate: (i) no trend in annual or seasonal rainfall totals, (ii) upward trend in runoff totals in the two urban catchments but not in the rural catchments, (iii) upward trend in dissolved oxygen and temperature in the urban catchments, but not in the rural catchments, and (iv) changes in temperature and dissolved oxygen in the urban catchments are not driven by climatic variables. PMID- 26802346 TI - Environmental land use conflicts in catchments: A major cause of amplified nitrate in river water. AB - Environmental land use conflicts are uses of the land that ignore soil capability. In this study, environmental land use conflicts were investigated in mainland Portugal, using Partial Least Squares (PLS) regression combined with GIS modeling and a group of 85 agricultural watersheds (with >50% occupation by agriculture) as work sample. The results indicate a dominance of conflicts in a region where vineyards systematically invaded steep hillsides (the River Douro basin), where forests would be the most appropriate use. As a consequence of the conflicts, nitrate concentrations in rivers and lakes from these areas have increased, sometimes beyond the legal limit of 50mg/L imposed by the European and Portuguese laws. Excessive nitrate concentrations were also observed along the Atlantic coast of continental Portugal, but associated to a combination of other factors: large population densities, and incomplete coverage by sewage systems and inadequate functioning of wastewater treatment plants. Before this study, environmental land use conflicts were never recognized as possible boost of nitrate concentrations in surface water. Bearing in mind the consequences of drinking water nitrate for human health, a number of land use change scenarios were investigated to forecast their impact on freshwater nitrate concentrations. It was seen that an aggravation of the conflicts would duplicate the number of watersheds with maximum nitrate concentrations above 50mg/L (from 11 to 20 watersheds), while the elimination of the conflicts would greatly reduce that number (to 3 watersheds). PMID- 26802347 TI - Detection of pharmaceuticals and phytochemicals together with their metabolites in hospital effluents in Japan, and their contribution to sewage treatment plant influents. AB - The occurrence of 41 pharmaceuticals and phytochemicals (PPs) including their metabolites was surveyed in hospital effluent in an urban area of Japan. A detailed survey of sewage treatment plant (STP) influent and effluent, and river water was also conducted. Finally, mass balances with mass fluxes of the target PPs through the water flow were evaluated and the degree of contribution of hospital effluent to the environmental discharge was estimated. The results indicate that 38 compounds were detectable in hospital effluent over a wide concentration range from ng/L to MUg/L, with a maximum of 92MUg/L. The contributions of PPs in the hospital effluent to STP influent varied widely from <0.1% to 14.8%. Although almost all of the remaining components could be removed below 1.0ng/L at STPs by the addition of ozone treatment, a number of PPs still remained above 10ng/L in STP effluent. These findings suggest the importance of applying highly developed treatments to hospital effluents and at STPs in the future to reduce the environmental risks posed by PPs. To our knowledge, this is the first demonstration of the presence of two conjugated metabolites of acetaminophen, acetaminophen glucuronide and acetaminophen sulfate, as well as of loxoprofen and loxoprofen alcohol, in hospital effluent, STP, and river waters. PMID- 26802348 TI - Impacts of future climate change on river discharge based on hydrological inference: A case study of the Grand River Watershed in Ontario, Canada. AB - Over the recent years, climate change impacts have been increasingly studied at the watershed scale. However, the impact assessment is strongly dependent upon the performance of the climatic and hydrological models. This study developed a two-step method to assess climate change impacts on water resources based on the Providing Regional Climates for Impacts Studies (PRECIS) modeling system and a Hydrological Inference Model (HIM). PRECIS runs provided future temperature and precipitation projections for the watershed under the Intergovernmental Panel on Climate Change SRES A2 and B2 emission scenarios. The HIM based on stepwise cluster analysis is developed to imitate the complex nonlinear relationships between climate input variables and targeted hydrological variables. Its robust mathematical structure and flexibility in predictor selection makes it a desirable tool for fully utilizing various climate modeling outputs. Although PRECIS and HIM cannot fully cover the uncertainties in hydro-climate modeling, they could provide efficient decision support for investigating the impacts of climate change on water resources. The proposed method is applied to the Grand River Watershed in Ontario, Canada. The model performance is demonstrated with comparison to observation data from the watershed during the period 1972-2006. Future river discharge intervals that accommodate uncertainties in hydro-climatic modeling are presented and future river discharge variations are analyzed. The results indicate that even though the total annual precipitation would not change significantly in the future, the inter-annual distribution is very likely to be altered. The water availability is expected to increase in Winter while it is very likely to decrease in Summer over the Grand River Watershed, and adaptation strategies would be necessary. PMID- 26802349 TI - Comprehensive monitoring of organic micro-pollutants in surface and groundwater in the surrounding of a solid-waste treatment plant of Castellon, Spain. AB - The solid-waste treatment plant of RECIPLASA is located in the municipality of Onda (Castellon province), which is an important agricultural area of Spain, with predominance of citrus crops. In this plant, all urban solid wastes from the town of Castellon (around 200,000 inhabitants) and other smaller towns as Almassora, Benicassim, Betxi, Borriana, L'Alcora, Onda and Vila-Real are treated. In order to evaluate the potential impact of this plant on the surrounding water, both surface and groundwater, a comprehensive monitoring of organic pollutants has been carried out along 2011, 2012 and 2013. To this aim, an advanced analytical strategy was applied for wide-scope screening, consisting on the complementary use of liquid chromatography (LC) and gas chromatography (GC) coupled to mass spectrometry (MS) with quadrupole (Q)-time of flight analyser (TOF). A generic solid-phase extraction with Oasis HLB cartridges was applied prior to the chromatographic analysis. The screening included more than 1500 organic pollutants as target compounds, such as pesticides, pharmaceuticals, veterinary drugs, drugs of abuse, UV-filters, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), among others. Pesticides, mainly herbicides, were the compounds more frequently detected. Other compounds as antioxidants, cosmetics, drugs of abuse, PAHs, pharmaceuticals and UV filters, were also identified in the screening though at much lower frequency. Once the screening was made, quantitative analysis focused on the compounds more frequently detected was subsequently applied using LC coupled to tandem MS with triple quadrupole analyser. In this way, up to 24 pesticides and transformation products (TPs), 7 pharmaceuticals, one drug of abuse and its metabolite could be quantified at sub-ppb concentrations. Along the three years of study, ten compounds were found at concentrations higher than 0.1MUg/L. Most of them were pesticides and TPs, a fact that illustrates that the main source of pollution seems to be the agricultural activities in this area. PMID- 26802350 TI - Impact of land cover changes and climate on the main airborne pollen types in Southern Spain. AB - Airborne pollen concentrations strongly correlate with flowering intensity of wind-pollinated species growing at and around monitoring sites. The pollen spectrum, and the variations in its composition and concentrations, is influenced by climatic features and by available nutritional resources but it is also determined by land use and its changes. The first factor influence is well known on aerobiological researches but the impact of land cover changes has been scarcely studied until now. This paper reports on a study carried out in Southern Spain (Cordoba city) examining airborne pollen trends over a 15-year period and it explores the possible links both to changes in land use and to climate variations. The Seasonal-Trend Decomposition procedure based on Loess (STL) which decomposes long-term data series into smaller seasonal component patterns was applied. Trends were compared with recorded changes in land use at varying distances from the city in order to determine their possible influence on pollen count variations. The influence of climate-related factors was determined by means of non-parametric correlation analysis. The STL method proved highly effective for extracting trend components from pollen time series, because their features vary widely and can change quickly in a short term. Results revealed mixed trends depending on the taxa and reflecting fluctuations in land cover and/or climate. A significant rising trend in Olea pollen counts was observed, attributable both to the increasing olive-growing area but also to changes in temperature and rainfall. Poaceae pollen concentrations also increased, due largely to an expansion of heterogeneous agricultural areas and to an increase in pollen season length positively influenced by rainfall and temperature. By contrast, the significant declining trend observed for pollen from ruderal taxa, such as Amaranthaceae, Rumex, Plantago and Urticaceae, may be linked to changes in urban planning strategies with a higher building pressure. PMID- 26802351 TI - First comparison of symptom data with allergen content (Bet v 1 and Phl p 5 measurements) and pollen data from four European regions during 2009-2011. AB - BACKGROUND: The level of symptoms in pollen allergy sufferers and users of the Patient's Hayfever Diary (PHD), does not directly reflect the total amount of pollen in the air. It is necessary to explain the symptom load and thus the development of allergic symptoms and to determine which environmental factors, besides the pollen load, influence variables. It seems reasonable to suspect allergen content because the amount of allergen varies throughout seasons and regions and is not always correlated with the total pollen amount. METHODS: Data on the allergen content of ambient air (Bet v 1 and Phl p 5) from 2009 until 2011 was used to compare the respective pollen and symptom loads for study regions in Austria, Germany, France and Finland. RESULTS: Our findings suggest that allergen amount (Bet v 1/Phl p 5) has a strong but regionally dependent impact on the symptom load of pollen allergy sufferers. Peak symptom loads can be traced with peak allergen loads. The influence of other important aeroallergens should also be assessed during the pollen season. CONCLUSION: Allergen concentrations have an impact on pollen allergy sufferers although not as clear as assumed previously. The pattern of pollen load and major allergen content distribution does not directly explain the symptom load pattern, although significant positive correlations were found. Thus, monitoring of symptoms via voluntary crowdsourcing should be considered for future pollen and symptom forecasts in order to support pollen allergy sufferers. PMID- 26802352 TI - Water Footprint of crop productions: A review. AB - Water Footprint is an indicator recently developed with the goal of quantifying the virtual content of water in products and/or services. It can also be used to identify the worldwide virtual water trade. Water Footprint is composed of three parts (green, blue and grey waters) that make the assessment complete in accordance with the Water Footprint Network and with the recent ISO14046. The importance of Water Footprint is linked to the need of taking consciousness about water content in products and services and of the achievable changes in productions, diets and market trades. In this study, a literature review has been completed on Water Footprint of agricultural productions. In particular, the focus was paid on crops for the production of food and bioenergy. From the review, the development of the Water Footprint concept emerged: in early studies the main goal was to assess products' water trade on a global scale, while in the subsequent years, the goal was the rigorous quantification of the three components for specific crops and in specific geographical areas. In the most recent assessments, similarities about the methodology and the employed tools emerged. For 96 scientific articles on Water Footprint indicator of agricultural productions, this literature review reports the main results and analyses weaknesses and strengths. Seventy-eight percent of studies aimed to quantify Water Footprint, while the remaining 22% analysed methodology, uncertainty, future trends and comparisons with other footprints. It emerged that most studies that quantified Water Footprint concerned cereals (33%), among which maize and wheat were the most investigated crops. In 46% of studies all the three components were assessed, while in 18% no indication about the subdivision was given; in the remaining 37%, only blue or green and blue components were quantified. PMID- 26802353 TI - Quantification of elemental and organic carbon in atmospheric particulate matter using color space sensing-hue, saturation, and value (HSV) coordinates. AB - A fast and cost effective application of color sensing was used to quantify color coordinates of atmospheric particulate matter collected on filters to quantify elemental and organic carbon (EC/OC) loading. This is a unique and novel approach for estimating OC composition. The method used a colorimeter and digital photography to obtain XYZ color space values and mathematically transformed them to HSV cylindrical-coordinates; a quantification method was applied to estimate the NIOSH and IMPROVE (TOR) EC/OC loadings from a set of globally diverse PM samples. When applied to 315 samples collected at three US EPA Chemical Speciation Network (CSN) sampling sites, the HSV model proved to be a robust method for EC measurement with an R(2)=0.917 for predicted versus measured loading results and a CV(RMSE)=16.1%. The OC quantified from the same sample filters had an R(2)=0.671 and a CV(RMSE)=24.8% between the predicted and measured results. The method was applied to NIOSH EC/OC results from a set of samples from rural China, Bagdad, and the San Joaquin Valley, CA, and the EC and OC CV(RMSE) were 30.8% and 49.3%, respectively. Additionally, the method was applied to samples with color quantified by a digital photographic image (DPI) with EC results showing good agreement with a CV(RMSE) of 22.6%. OC concentrations were not captured as accurately with the DPI method, with a CV(RMSE) of 77.5%. The method's low analytical cost makes it a valuable tool for estimating EC/OC exposure in developing regions and for large scale monitoring campaigns. PMID- 26802354 TI - Metabolic profiling of residents in the vicinity of a petrochemical complex. AB - No previous studies have simultaneously measured the biomarkers of environmental exposure and metabolome perturbation in residents affected by industrial pollutants. This study aimed to investigate the metabolic effects of environmental pollutants such as vanadium and polycyclic aromatic hydrocarbons (PAHs) on residents in the vicinity of a petrochemical complex. The study subjects were 160 residents, including 80 high-exposure subjects exposed to high levels of vanadium and PAHs and 80 age- and gender-matched low-exposure subjects living within a 40-km radius of a petrochemical complex. The exposure biomarkers vanadium and 1-hydroxypyrene and four oxidative/nitrosative stress biomarkers were measured in these subjects. Plasma samples from the study subjects were also analyzed using (1)H NMR spectroscopy for metabolic profiling. The results showed that the urinary levels of vanadium and 1-hydroxypyrene in the high-exposure subjects were 40- and 20-fold higher, respectively, than those in the low exposure subjects. Higher urinary levels of stress biomarkers, including 8-OHdG, HNE-MA, 8-isoPF2alpha, and 8-NO2Gua, were also observed among the high-exposure subjects compared with the low-exposure subjects. Partial least squares discriminant analysis of the plasma metabolome demonstrated a clear separation between the high- and low-exposure subjects; the intensities of amino acids and carbohydrate metabolites were lower in the high-exposure subjects compared with the low-exposure subjects. The exposure to vanadium and PAHs may cause a reduction in the levels of amino acids and carbohydrates by elevating PPAR and insulin signaling, as well as oxidative/nitrosative stress. PMID- 26802355 TI - Quantitative microbial risk assessment combined with hydrodynamic modelling to estimate the public health risk associated with bathing after rainfall events. AB - This study investigated the public health risk from exposure to infectious microorganisms at Sandvika recreational beaches, Norway and dose-response relationships by combining hydrodynamic modelling with Quantitative Microbial Risk Assessment (QMRA). Meteorological and hydrological data were collected to produce a calibrated hydrodynamic model using Escherichia coli as an indicator of faecal contamination. Based on average concentrations of reference pathogens (norovirus, Campylobacter, Salmonella, Giardia and Cryptosporidium) relative to E. coli in Norwegian sewage from previous studies, the hydrodynamic model was used for simulating the concentrations of pathogens at the local beaches during and after a heavy rainfall event, using three different decay rates. The simulated concentrations were used as input for QMRA and the public health risk was estimated as probability of infection from a single exposure of bathers during the three consecutive days after the rainfall event. The level of risk on the first day after the rainfall event was acceptable for the bacterial and parasitic reference pathogens, but high for the viral reference pathogen at all beaches, and severe at Kalvoya-small and Kalvoya-big beaches, supporting the advice of avoiding swimming in the day(s) after heavy rainfall. The study demonstrates the potential of combining discharge-based hydrodynamic modelling with QMRA in the context of bathing water as a tool to evaluate public health risk and support beach management decisions. PMID- 26802357 TI - An appraisal of precipitation distribution in the high-altitude catchments of the Indus basin. AB - Scarcity of in-situ observations coupled with high orographic influences has prevented a comprehensive assessment of precipitation distribution in the high altitude catchments of Indus basin. Available data are generally fragmented and scattered with different organizations and mostly cover the valleys. Here, we combine most of the available station data with the indirect precipitation estimates at the accumulation zones of major glaciers to analyse altitudinal dependency of precipitation in the high-altitude Indus basin. The available observations signified the importance of orography in each sub-hydrological basin but could not infer an accurate distribution of precipitation with altitude. We used Kriging with External Drift (KED) interpolation scheme with elevation as a predictor to appraise spatiotemporal distribution of mean monthly, seasonal and annual precipitation for the period of 1998-2012. The KED-based annual precipitation estimates are verified by the corresponding basin-wide observed specific runoffs, which show good agreement. In contrast to earlier studies, our estimates reveal substantially higher precipitation in most of the sub-basins indicating two distinct rainfall maxima; 1st along southern and lower most slopes of Chenab, Jhelum, Indus main and Swat basins, and 2nd around north-west corner of Shyok basin in the central Karakoram. The study demonstrated that the selected gridded precipitation products covering this region are prone to significant errors. In terms of quantitative estimates, ERA-Interim is relatively close to the observations followed by WFDEI and TRMM, while APHRODITE gives highly underestimated precipitation estimates in the study area. Basin-wide seasonal and annual correction factors introduced for each gridded dataset can be useful for lumped hydrological modelling studies, while the estimated precipitation distribution can serve as a basis for bias correction of any gridded precipitation products for the study area. PMID- 26802356 TI - Assessing the risk associated with the presence of emerging organic contaminants in sludge-amended soil: A country-level analysis. AB - Greece was used as case study and the environmental risk associated with the existence of 99 emerging organic contaminants (EOCs) in sludge-amended soil was estimated using risk quotient (RQ) approach. Data on the concentration levels of EOCs in sewage sludge was collected after literature review. Chemical analyses were also conducted for 50 pharmaceuticals and illicit drugs in sludge samples from Athens Sewage Treatment Plant. Risk assessment was based on both terrestrial and aquatic acute toxicity data, using both the maximum and the average measured concentrations of the target compounds. EC50/LC50 values were collected through literature review or using the ECOSAR program in cases that experimental values were not available. Triclosan seems to pose an environmental risk on the soil environment, as its RQ values exceeded 1, both in terrestrial and aquatic toxicity data based risk assessment. Calculations based on aquatic toxicity data showed that another eleven compounds had RQs higher than 1, most of them belonging to the classes of synthetic phenolic compounds and siloxanes. Tetradecamethylhexasiloxane presented the highest RQ, while high RQs were also calculated for decamethylcyclopentasiloxane and caffeine. No environmental risk for the terrestrial environment is expected due to the individual action of illicit drugs, perfluorinated compounds and benzotriazoles. The sludge source and the day of sampling affected the estimated threat due to nonylphenolic compounds; however these factors did not affect the estimated risk for siloxanes, caffeine and ofloxacin. Calculation of RQ values for the mixture of EOCs, using either the maximum or the average concentrations, far exceeded 1 (253 and 209, respectively), indicating a presumable threat for the terrestrial environment due to the baseline toxicity of these compounds. Countries that reuse sludge for agricultural purposes should include specific EOCs in national monitoring campaigns and study more thoroughly on their effects to the terrestrial environment. PMID- 26802358 TI - Sr isotope tracing of multiple water sources in a complex river system, Notec River, central Poland. AB - Anthropogenic impact on surface waters and other elements in the environment was investigated in the Notec River basin in central Poland. The approach was to trace changes in the Sr isotope composition ((87)Sr/(86)Sr) and concentration in space and time. Systematic sampling of the river water shows a very wide range of (87)Sr/(86)Sr ratios, from 0.7089 to 0.7127. This strong variation, however, is restricted to the upper course of the river, whereas the water in the lower course typically shows (87)Sr/(86)Sr values around 0.7104-0.7105. Variations in (87)Sr/(86)Sr are associated with a wide range of Sr concentrations, from 0.14 to 1.32mg/L. We find that strong variations in (87)Sr/(86)Sr and Sr concentrations can be accounted for by mixing of two end-members: 1) atmospheric waters charged with Sr from the near-surface weathering and wash-out of Quaternary glaciogenic deposits, and 2) waters introduced into the river from an open pit lignite mine. The first reservoir is characterized by a low Sr content and high (87)Sr/(86)Sr ratios, whereas mine waters display opposite characteristics. Anthropogenic pollution is also induced by extensive use of fertilizers which constitute the third source of Sr in the environment. The study has an important implication for future archeological studies in the region. It shows that the present-day Sr isotope signatures of river water, flora and fauna cannot be used unambiguously to determine the "baseline" for bioavailable (87)Sr/(86)Sr in the past. PMID- 26802359 TI - New Ligand Binding Function of Human Cerberus and Role of Proteolytic Processing in Regulating Ligand-Receptor Interactions and Antagonist Activity. AB - Cerberus is a key regulator of vertebrate embryogenesis. Its biological function has been studied extensively in frog and mouse embryos. Its ability to bind and antagonize the transforming growth factor-beta (TGF-beta) family ligand Nodal is well established. Strikingly, the molecular function of Cerberus remains poorly understood. The underlying reason is that Cerberus is a complex, multifunctional protein: It binds and inhibits multiple TGF-beta family ligands, it may bind and inhibit some Wnt family members, and two different forms with distinct activities have been described. In addition, sequence homology between frog and mammalian Cerberus is low, suggesting that previous studies, which analyzed frog Cerberus function, may not accurately describe the function of mammalian Cerberus. We therefore undertook to determine the molecular activities of human Cerberus in TGF-beta family signaling. Using purified proteins, surface plasmon resonance, and reporter gene assays, we discovered that human Cerberus bound and inhibited the TGF-beta family ligands Activin B, BMP-6, and BMP-7, but not the frog Cerberus ligand BMP-2. Notably, full-length Cerberus successfully blocked ligand binding to type II receptors, but the short form was less effective. In addition, full-length Cerberus suppressed breast cancer cell migration but the short form did not. Thus, our findings expand the roles of Cerberus as TGF-beta family signaling inhibitor, provide a molecular rationale for the function of the N terminal region, and support the idea that Cerberus could have regulatory activities beyond direct inhibition of TGF-beta family signaling. PMID- 26802360 TI - Effects of FTY720 on peripheral blood lymphocytes and graft infiltrating cells in a rat model of chronic renal allograft rejection. AB - AIMS: Chronic renal allograft loss is still an unsolved problem in kidney transplantation. We evaluated the impact of FTY720, a S1P receptor agonist, known to deplete lymphocytes from the peripheral blood by sequestering them into lymph nodes and Peyer's patches, on blood lymphocytes and graft infiltrating cells in a rat model of chronic real allograft rejection. METHODS: LEW rats served as recipients for LEW.1U7B kidney grafts. All animals were treated with CsA (5mg/kg) for 10 days after renal transplantation and monitored for kidney function, peripheral blood lymphocytes and graft infiltrating cells. In the intervention group (n=7) FTY720 therapy was started 7 weeks post-KTx in a dose of 0.5 mg/kg p. o. three times a week. RESULTS: In the control group the survival of the rats was 9, 11, 18 and 4 * 24 weeks, in the intervention group 2 * 8, 9, 2 * 11, 18 and 20 weeks. While in the intervention group the number of T- and B-lymphocytes in the peripheral blood was successfully reduced during FTY720 treatment, both groups showed significant amounts of T- and B-lymphocytes in the kidney grafts. Animals in both groups developed donor specific antibodies, extensive albuminuria and severe chronic changes in the grafts. CONCLUSIONS: FTY720 was highly effective to reduce T- and B-lymphocytes in the peripheral blood, but not effective in clearing their infiltration in the graft. Graft survival was not prolonged by FTY720 treatment starting late after kidney transplantation. PMID- 26802361 TI - Providing Appropriate Risk Information on Genome Editing for Patients. AB - Genome editing, represented by CRISPR/Cas9, facilitates somatic and germline gene modifications in many species, including humans. However, one of key issues, off target mutation deserves special consideration prior to clinical applications. We herein discuss the importance of risk information on genome editing for obtaining legitimate patient consent and social acceptance. PMID- 26802362 TI - Carbon dioxide emission from bamboo culms. AB - Bamboos are one of the fastest growing plants on Earth, and are widely considered to have high ability to capture and sequester atmospheric carbon, and consequently to mitigate climate change. We tested this hypothesis by measuring carbon dioxide (CO2 ) emissions from bamboo culms and comparing them with their biomass sequestration potential. We analysed diurnal effluxes from Bambusa vulgaris culm surface and gas mixtures inside hollow sections of various bamboos using gas chromatography. Corresponding variations in gas pressure inside the bamboo section and culm surface temperature were measured. SEM micrographs of rhizome and bud portions of bamboo culms were also recorded. We found very high CO2 effluxes from culm surface, nodes and buds of bamboos. Positive gas pressure and very high concentrations of CO2 were observed inside hollow sections of bamboos. The CO2 effluxes observed from bamboos were very high compared to their carbon sequestration potential. Our measurements suggest that bamboos are net emitters of CO2 during their lifespan. PMID- 26802363 TI - New marine natural products from sponges (Porifera) of the order Dictyoceratida (2001 to 2012); a promising source for drug discovery, exploration and future prospects. AB - The discovery of new drugs can no longer rely primarily on terrestrial resources, as they have been heavily exploited for over a century. During the last few decades marine sources, particularly sponges, have proven to be a most promising source of new natural products for drug discovery. This review considers the order Dictyoceratida in the Phylum Porifera from which the largest number of new marine natural products have been reported over the period 2001-2012. This paper examines all the sponges from the order Dictyoceratida that were reported as new compounds during the time period in a comprehensive manner. The distinctive physical characteristics and the geographical distribution of the different families are presented. The wide structural diversity of the compounds produced and the variety of biological activities they exhibited is highlighted. As a representative of sponges, insights into this order and avenues for future effective natural product discovery are presented. The research institutions associated with the various studies are also highlighted with the aim of facilitating collaborative relationships, as well as to acknowledge the major international contributors to the discovery of novel sponge metabolites. The order Dictyoceratida is a valuable source of novel chemical structures which will continue to contribute to a new era of drug discovery. PMID- 26802364 TI - Cognitive control adjustments in healthy older and younger adults: Conflict adaptation, the error-related negativity (ERN), and evidence of generalized decline with age. AB - Older adults display alterations in neural reflections of conflict-related processing. We examined response times (RTs), error rates, and event-related potential (ERP; N2 and P3 components) indices of conflict adaptation (i.e., congruency sequence effects) a cognitive control process wherein previous-trial congruency influences current-trial performance, along with post-error slowing, correct-related negativity (CRN), error-related negativity (ERN) and error positivity (Pe) amplitudes in 65 healthy older adults and 94 healthy younger adults. Older adults showed generalized slowing, had decreased post-error slowing, and committed more errors than younger adults. Both older and younger adults showed conflict adaptation effects; magnitude of conflict adaptation did not differ by age. N2 amplitudes were similar between groups; younger, but not older, adults showed conflict adaptation effects for P3 component amplitudes. CRN and Pe, but not ERN, amplitudes differed between groups. Data support generalized declines in cognitive control processes in older adults without specific deficits in conflict adaptation. PMID- 26802365 TI - Itsy bitsy spider?: Valence and self-relevance predict size estimation. AB - The current study explored the role of valence and self-relevance in size estimation of neutral and aversive animals. In Experiment 1, participants who were highly fearful of spiders and participants with low fear of spiders rated the size and unpleasantness of spiders and other neutral animals (birds and butterflies). We found that although individuals with both high and low fear of spiders rated spiders as highly unpleasant, only the highly fearful participants rated spiders as larger than butterflies. Experiment 2 included additional pictures of wasps (not self-relevant, but unpleasant) and beetles. The results of this experiment replicated those of Experiment 1 and showed a similar bias in size estimation for beetles, but not for wasps. Mediation analysis revealed that in the high-fear group both relevance and valence influenced perceived size, whereas in the low-fear group only valence affected perceived size. These findings suggest that the effect of highly relevant stimuli on size perception is both direct and mediated by valence. PMID- 26802366 TI - Interaction of posttetanic potentiation and the catchlike property in mouse skeletal muscle. AB - INTRODUCTION: Posttetanic potentiation (PTP) and the catchlike property (CLP) enhance contractile function in skeletal muscle. We investigated the CLP during dynamic performance in mouse hindlimb muscles with (wild-type) and without (skMLCK(-/-) ) the primary mechanism for PTP (myosin phosphorylation) (in vitro, 25 degrees C). METHODS: Extensor digitorum longus muscles of both genotypes were stimulated with constant frequency and catchlike trains (CFT and CLT), before and after a potentiating stimulus (PS). RESULTS: Before the PS, the CLT increased concentric force/work relative to the CFT, but this effect was greater for skMLCK(-/-) than wild-type muscles. After the PS, the catchlike effect was reduced in wild-type muscles but unchanged in skMLCK(-/-) muscles that did not display PTP. CONCLUSIONS: These data suggest that PTP interferes with the CLP during concentric force development at moderate speeds of shortening. We conclude that the physiological utility of each mechanism and their interactions provide important modulations to fast skeletal muscle function. Muscle Nerve 54: 308-316, 2016. PMID- 26802368 TI - A new normal?: Women's experiences of biographical disruption and liminality following treatment for early stage breast cancer. AB - Increasing numbers of women are surviving breast cancer, but little is known about the long-term implications of having survived a life-threatening illness and living with embodied reminders of its potential to return. Twenty-four women aged between 42 and 80 (median = 51)who had been treated for early stage breast cancer in the UK between 6 months and 29 years previously, were recruited through local media and interviewed. Analysis of their narratives revealed challenges in the post-treatment period that were conceptualised as biographical disruption and liminality. Although no longer ill, an ongoing fear of recurrence combined with embodied changes prevented a return to 'normal' i.e. a pre-cancer state in terms of health status, identity and relationships. We argue that following the biographical disruption of breast cancer, a 'new normal' entails a continual renegotiation of identities, daily lives and futures as time passes and lives evolve. PMID- 26802369 TI - Life course socioeconomic status and the decline in information processing speed in late life. AB - Low socio-economic status is a recognised composite measure made up of income, education and occupational social class, which is a risk factor for poor physical and mental health and late life dementia. Here, we distinguish between components of childhood socioeconomic status to explore their separate influences of childhood and adult occupational social class (OSC), childhood mental ability and education on late life cognitive ability and change trajectories. Cognitive data were collected longitudinally from a sub-sample (N = 478) of the Aberdeen 1936 birth cohort tested on up to 5 occasions between ages 63 and 78 years. Age 11 mental ability scores were available for all participants. We used longitudinal multi-level linear modelling to explore models of cognitive change that distinguished between the possible influences of parental occupation, participants' own occupation as adults, duration of formal education, childhood mental ability and the participants' own occupation. We showed that parental occupation and the participants' own occupation are independently associated with cognition in late life, but do not influence the trajectory of cognitive change. However, when models include childhood mental ability and education the influence of parental and participant occupation is no longer significant. The association in these data between parental occupation and late life cognitive variation is accounted for by childhood mental ability and duration of formal education. However, we cannot exclude the possibility that parental occupation in early life influences early life mental ability and duration of education. The trajectory of change with age is similar across all models, with none of the life course factors (education, parental and participant occupational social class and childhood ability) significantly co-varying with the trajectory of cognitive variation. PMID- 26802370 TI - Nuancing stigma through ethnography: the case of cutaneous leishmaniasis in Suriname. AB - Health-related stigma and its dramatic consequences for those stigmatized have long been a crucial concern for public health authorities globally. However, before concluding that stigma spoils the lives of people with a particular disease or disability and is a major obstacle to obtaining/providing adequate health care, it is necessary to first determine whether there is actual stigmatization related to the condition concerned. The purpose of this article is to nuance the concept of stigma through a detailed ethnographic exploration of the experiences and views of patients and others affected by the parasitic skin disease cutaneous leishmaniasis (CL) in Suriname, South America. Qualitative data on the perceptions, treatment and illness experiences of CL in Suriname was collected in 2009 and 2010 among 205 CL patients at the Dermatology Service in the capital city Paramaribo, and among 321 people in different rural hinterland villages. The exploration reveals the complex and sometimes confusing statements of patients and observers of social reactions to the disease. The authors conclude that--in contrast to other societies--CL is not generally a stigmatized disease in Suriname (though this is not to deny that stigmatization may occur occasionally). Over the past decades, the concepts of stigma and stigmatization have been abundantly theorized. But when theory drifts away from ethnographic evidence, it may turn into imprecise popular speech. In this article, we warn against inflation of the term stigma and show, through an in-depth qualitative description of reactions to symptoms of CL in Suriname, why negative reactions may not necessarily entail stigma. PMID- 26802367 TI - Functional MRI of emotional memory in adolescent depression. AB - INTRODUCTION: Major Depressive Disorder (MDD) is a leading cause of disease burden worldwide. Mood-congruent biases in memory tasks are frequently reported in MDD patients, with facilitated memory for negative stimuli. Most functional MRI studies to date have examined the neural correlates of these biases in depressed adults, with fewer studies in adolescents with MDD. Investigation of MDD in adolescence may aid greater understanding of the aetiology and development of the disorder. METHODS: Cognitive biases were investigated in 56 MDD patients aged 11-17 years and a matched group of 30 healthy control participants with a self-referential memory task. Behavioural performance and BOLD fMRI data were collected during both encoding and retrieval stages. RESULTS: The neural response to encoding in adolescents with MDD was found to differ significantly from controls. Additionally, neural responses during encoding and retrieval showed differential relationships with age between patient and control groups, specifically in medial, temporal, and prefrontal regions. CONCLUSIONS: These findings suggest that during adolescence neurophysiological activity associated with emotional memory differs in those with depression compared to controls and may be age sensitive. PMID- 26802372 TI - Morphing Compression Garments for Space Medicine and Extravehicular Activity Using Active Materials. AB - INTRODUCTION: Compression garments tend to be difficult to don/doff, due to their intentional function of squeezing the wearer. This is especially true for compression garments used for space medicine and for extravehicular activity (EVA). We present an innovative solution to this problem by integrating shape changing materials-NiTi shape memory alloy (SMA) coil actuators formed into modular, 3D-printed cartridges-into compression garments to produce garments capable of constricting on command. METHODS: A parameterized, 2-spring analytic counterpressure model based on 12 garment and material inputs was developed to inform garment design. A methodology was developed for producing novel SMA cartridge systems to enable active compression garment construction. Five active compression sleeve prototypes were manufactured and tested: each sleeve was placed on a rigid cylindrical object and counterpressure was measured as a function of spatial location and time before, during, and after the application of a step voltage input. RESULTS: Controllable active counterpressures were measured up to 34.3 kPa, exceeding the requirement for EVA life support (29.6 kPa). Prototypes which incorporated fabrics with linear properties closely matched analytic model predictions (4.1%/-10.5% error in passive/active pressure predictions); prototypes using nonlinear fabrics did not match model predictions (errors >100%). Pressure non-uniformities were observed due to friction and the rigid SMA cartridge structure. DISCUSSION: To our knowledge this is the first demonstration of controllable compression technology incorporating active materials, a novel contribution to the field of compression garment design. This technology could lead to easy-to-don compression garments with widespread space and terrestrial applications. PMID- 26802374 TI - Wearable Accelerometers in High Performance Jet Aircraft. AB - INTRODUCTION: Wearable accelerometers have become ubiquitous in the fields of exercise physiology and ambulatory hospital settings. However, these devices have yet to be validated in extreme operational environments. The objective of this study was to correlate the gravitational forces (G forces) detected by wearable accelerometers with the G forces detected by high performance aircraft. METHODS: We compared the in-flight G forces detected by the two commercially available portable accelerometers to the F/A-18 Carrier Aircraft Inertial Navigation System (CAINS-2) during 20 flights performed by the Navy's Flight Demonstration Squadron (Blue Angels). Postflight questionnaires were also used to assess the perception of distractibility during flight. RESULTS: Of the 20 flights analyzed, 10 complete in-flight comparisons were made, accounting for 25,700 s of correlation between the CAINS-2 and the two tested accelerometers. Both accelerometers had strong correlations with that of the F/A-18 Gz axis, averaging r = 0.92 and r = 0.93, respectively, over 10 flights. Comparison of both portable accelerometer's average vector magnitude to each other yielded an average correlation of r = 0.93. Both accelerometers were found to be minimally distracting. DISCUSSION: These results suggest the use of wearable accelerometers is a valid means of detecting G forces during high performance aircraft flight. Future studies using this surrogate method of detecting accelerative forces combined with physiological information may yield valuable in-flight normative data that heretofore has been technically difficult to obtain and hence holds the promise of opening the door for a new golden age of aeromedical research. PMID- 26802373 TI - Exercise Responses to Gravity-Independent Flywheel Aerobic and Resistance Training. AB - BACKGROUND: Although several exercise systems have been developed to mitigate the physiological deconditioning that occurs in microgravity, few have the capacity to positively impact multiple physiological systems and still meet the volume/mass requirements needed for missions beyond low Earth orbit. The purpose of this study was to test the gravity-independent Multi-Mode Exercise Device (M MED) for both resistance (RE) and aerobic (AE) training stimuli. METHODS: Eight men and nine women (mean age 22.0 +/- 0.4 yr) completed 5 wk of training on the M MED: RE 4 * 7 squats 2 d/wk, and AE 4 * 4-min rowing bouts at ~90% Vo2max 3 d/wk. Pre- and post-training data collection included an aerobic capacity test, MR imaging, strength testing, and vastus lateralis muscle biopsy. RESULTS: Vo2max increased 8%, 3RM strength 18%, and quadriceps femoris cross-sectional area (CSA) 10%. Knee extensor strength increased at all isokinetic speeds tested. Subjects also demonstrated improved fatigue resistance in knee extension. At the cellular and molecular level, the biopsy revealed increases in mixed myofiber CSA (13%), citrate synthase activity (26%), total RNA concentration (24%), IGF-I mRNA (77%), and Type IIa myosin heavy chain (MHC) mRNA (8%), and a concomitant decrease in Type IIx MHC mRNA (-23%). None of the changes were gender-specific. DISCUSSION: Both the functional outcomes and biomarker changes indicate that a very low volume of M-MED exercise results in robust adaptation in the cardiovascular and musculoskeletal systems. The M-MED has the potential to provide a wide range of countermeasure exercises and should be considered for testing in ground-based spaceflight simulation. PMID- 26802375 TI - Hypoxia and Coriolis Illusion in Pilots During Simulated Flight. AB - INTRODUCTION: Pilots' vision and flight performance may be impeded by spatial disorientation and high altitude hypoxia. The Coriolis illusion affects both orientation and vision. However, the combined effect of simultaneous Coriolis illusion and hypoxia on saccadic eye movement has not been evaluated. METHOD: A simulated flight was performed by 14 experienced pilots under 3 conditions: once under normal oxygen partial pressure and twice under reduced oxygen partial pressures, reflecting conditions at 5000 m and 6000 m (16,404 and 19,685 ft), respectively. Eye movements were evaluated with a saccadometer. RESULTS: At normal oxygen pressure, Coriolis illusion resulted in 55% and 31% increases in mean saccade amplitude and duration, respectively, but a 32% increase in mean saccade frequency was only noted for saccades smaller than the angular distance between cockpit instruments, suggesting an increase in the number of correction saccades. At lower oxygen pressures a pronounced increase in the standard deviation of all measures was noticed; however, the pattern of changes remained unchanged. DISCUSSION: Simple measures of saccadic movement are not affected by short-term hypoxia, most likely due to compensatory mechanisms. PMID- 26802376 TI - Missing Aircraft Crash Sites and Spatial Relationships to the Last Radar Fix. AB - BACKGROUND: Few studies have examined the spatial characteristics of missing aircraft in actual distress. No previous studies have looked at the distance from the last radar plot to the crash site. The purpose of this study was to characterize this distance and then identify environmental and flight characteristics that might be used to predict the spatial relationship and, therefore, aid search and rescue planners. METHODS: Detailed records were obtained from the U.S. Air Force Rescue Coordination Center for missing aircraft in distress from 2002 to 2008. The data was combined with information from the National Transportation Safety Board (NTSB) Accident Database. The spatial relationship between the last radar plot and crash site was then determined using GIS analysis. RESULTS: A total of 260 missing aircraft incidents involving 509 people were examined, of which 216 (83%) contained radar information. Among the missing aircraft the mortality rate was 89%; most occurred in mountainous terrain (57%); Part 91 flight accounted for 95% of the incidents; and 50% of the aircraft were found within 0.8 nmi from the last radar plot. Flight characteristics, descent rate, icing conditions, and instrument flight rule vs. visual flight rule flight could be used to predict spatial characteristics. CONCLUSIONS: In most circumstances, the last radar position is an excellent predictor of the crash site. However, 5% of aircraft are found further than 45.4 nmi. The flight and environmental conditions were identified and placed into an algorithm to aid search planners in determining how factors should be prioritized. PMID- 26802377 TI - Gastrointestinal Disease in Pilots, 2001-2013. AB - INTRODUCTION: The frequency and distribution of gastrointestinal (GI) disease in the population of active duty Air Force pilots is poorly understood, even though GI illness can temporarily or permanently lead to disqualification from flying duties. Better understanding of GI disease within this population could yield considerable operational risk and human performance insight and provide data to use in assessing the effectiveness of current medical standards related to flight training and flying duties. METHODS: A dataset reflecting inpatient and outpatient healthcare visits from 2001 through 2013 was developed and reviewed. Gastrointestinal illness was grouped into 18 subcategories of disease, and the frequency and distribution of visits for these categories were tallied. The total burden of GI illness over the target dates was compared between pilots, nonpilot aircrew/special operational duty personnel, and nonaircrew/nonspecial duty personnel. RESULTS: Esophageal disease and dyspeptic conditions were the two most frequently encountered diagnoses among all three population groups, comprising almost 50% of the gastrointestinal diagnoses in age and gender-matched samples of all three populations. The overall burden of disease over the total timeframe of the study was not statistically different in the three populations, with a median of four encounters per person for GI disease. Of interest, the total burden of disease increased over the course of the study period in all populations, driven in large measure by increases in esophageal disease and dyspeptic conditions. DISCUSSION: The general distribution and overall burden of GI disease in populations of Air Force pilots, nonpilot aircrew/special operational duty personnel, and nonaircrew/nonspecial duty personnel were similar. The increase in esophageal and dyspeptic conditions over time warrants further attention. PMID- 26802378 TI - Subjective Vertical Conflict Theory and Space Motion Sickness. AB - BACKGROUND: Space motion sickness (SMS) remains a troublesome problem during spaceflight. The subjective vertical (SV) conflict theory postulates that all motion sickness provoking situations are characterized by a condition in which the SV sensed from gravity and visual and idiotropic cues differs from the expected vertical. This theory has been successfully used to predict motion sickness in different vehicles on Earth. METHOD: We have summarized the most outstanding and recent studies on the illusions and characteristics associated with spatial disorientation and SMS during weightlessness, such as cognitive map and mental rotation, the visual reorientation and inversion illusions, and orientation preferences between visual scenes and the internal z-axis of the body. RESULTS: The relationships between the SV and the incidence of and susceptibility to SMS as well as spatial disorientation were addressed. CONCLUSION: A consistent framework was presented to understand and explain SMS characteristics in more detail on the basis of the SV conflict theory, which is expected to be more advantageous in SMS prediction, prevention, and training. PMID- 26802379 TI - Incidence and Features of Barodontalgia Among Military Divers. AB - OBJECTIVE: Divers are vulnerable to barodontalgia (atmospheric pressure change related dental pain), which may jeopardize diving safety and mission completion. Our aim was to investigate the experience of barodontalgia among western military divers. METHODS: French Armed Forces diving personnel were asked to answer a structured questionnaire including questions regarding their oral health, diving and career features, and barodontalgia while diving. For analysis, the participants were divided into commando/clearance divers (Group A) and ship divers (Group B). RESULTS: All the requested 1389 divers agreed to participate in the study (100%) and 1317 divers (94.8%) who fully completed the questionnaire were included in the analysis. Of these 1317 individuals, 96 (7.3%) suffered from at least 1 episode of barodontalgia while diving, with a total of 119 episodes of barodontalgia. Barodontalgia was more frequent in the upper (62.2%) than the lower dentition (37.8%) (OR = 2.7; 95% CI, 1.6-4.5) and appeared more common during descent (77.3%) than ascent (22.7%) (OR = 11.6; 95% CI, 6.3-31.3). Barodontalgia experience was higher in divers who have an examination less than once per year (14.5%) in comparison to divers who usually have a dental examination once a year or more (6.3%) (OR = 2.5; 95% CI, 1.5-4.2). DISCUSSION: Barodontalgia mostly appeared in the maxilla and during descent; therefore, a great role for barosinusitis in the etiology of oral pain while diving may be suggested. The infrequent experience of barodontalgia in divers who routinely visit the dentist once a year or more suggests that the risk of barodontalgia might decrease with the maintenance of a good oral status. PMID- 26802380 TI - Transient Unilateral Facial Nerve Baroparesis with Vertigo on Ascent in the F 16CM. AB - BACKGROUND: Presented is a rare case of transient unilateral facial nerve paralysis occurring in a pilot while on initial ascent in an F-16CM. This pathology is sporadically observed in the diving community, but rarely described in military or civil aviation. This case was particularly unusual in its promptness of onset, rapid recovery, and its association with vertigo. CASE REPORT: This case report describes a previously healthy 26-yr-old F-16 pilot who experienced ear block and subsequent unilateral facial paralysis while on initial ascent. This was relieved quickly after clearing the affected ear without any neurological sequelae. A second episode was associated with vertigo in addition to the ear block and facial symptoms. Both episodes were separated by 3 d. DISCUSSION: Barotrauma to the facial nerve via an uncovered or "dehiscent" facial nerve canal was suggested by the clinical course, computed tomography, and confirmed by expert consultation. Making the diagnosis in an aviator, especially the military aviator, is important for safety of flight, to avoid unwarranted diagnostics, and to minimize operational impact. A mechanism for the aviator's associated vertigo is suggested. PMID- 26802381 TI - Hypercapnic Respiratory Acidosis During An In-Flight Oxygen Assessment. AB - BACKGROUND: Patients with respiratory disease are at risk of excessive hypoxemia in the hypobaric commercial aircraft cabin environment, and the consensus is that this is easily corrected with supplementary oxygen. However, despite the risks of hypercapnia with increasing inspired oxygen in some patients being well established, this issue is not currently addressed in medical guidelines for air travel. CASE REPORT: A 76-yr-old woman with chronic type 2 respiratory failure underwent hypoxic challenge testing (HCT) to assess in-flight oxygen requirements. She is stable on home ventilation, and baseline arterial blood gases showed mild hypoxemia (Pao2 9.12 kPa), normal P(a)co(2) (5.64 kPa) and pH (7.36) with 98% S(p)O(2). HCT was performed delivering 15% FIo(2) via a mask, and the patient desaturated to < 85%. HCT blood gases revealed significant hypoxemia (P(a)o(2) < 6.6 kPa), indicating in-flight oxygen. Continuous oxygen at 2 L . min 1 via nasal cannula corrected the hypoxia, although P(a)co(2) increased to 6.9 kPa with reduction in pH to the threshold of severe respiratory acidosis (pH 7.25). The patient was advised against flying due to hypoxemia during HCT and the precipitous drop in pH on oxygen. DISCUSSION: It is possible to hyperoxygenate patients with type 2 respiratory failure in flight with the minimum level of supplementary oxygen available on many aircraft. In these cases P(a)co(2) and pH should be scrutinized during HCT before recommending in-flight oxygen. No current guidelines discuss the risk of hypercapnia from in-flight oxygen; it is therefore recommended that this be addressed in future revisions of medical air travel guidelines, should further research indicate it. PMID- 26802382 TI - Letter to the Editor re: Use of Statins for Prophylaxis Against Acute Mountain Sickness: Response. PMID- 26802383 TI - Letter to the Editor re: Use of Statins for Prophylaxis Against Acute Mountain Sickness: Letter. PMID- 26802384 TI - You're the Flight Surgeon: vestibular neuritis. AB - Brown MR. You're the flight surgeon: vestibular neuritis. Aerosp Med Hum Perform. 2016; 87(2):150-152. PMID- 26802385 TI - You're the Flight Surgeon: erectile dysfunction. AB - Puchta P. You're the flight surgeon: erectile dysfunction. Aerosp Med Hum Perform. 2016; 87(2):152-155. PMID- 26802386 TI - This Month in Aerospace Medicine History. PMID- 26802389 TI - In Honor of Nurses Week: A Commitment to Ethical Practice and Quality Care. PMID- 26802388 TI - Risk of thromboembolism in patients with hereditary angioedema treated with plasma-derived C1-inhibitor. AB - BACKGROUND: Plasma-derived C1-inhibitor (C1-INH) concentrates (pdC1-INH) have been used as safe and effective treatments for hereditary angioedema with C1-INH deficiency (C1-INH-HAE) for >30 years. Notwithstanding this, sporadic reports and a study into the high-dose therapy of neonates with C1-INH concentrate administered in an off-label indication raised concerns that this drug might increase the risk of thromboembolism. OBJECTIVE: To investigate the incidence of thromboembolism and the background of the risk factors related to treatment with pdC1-INH. METHODS: Our retrospective cohort study of 144 patients with C1-INH-HAE compared the incidence of thromboembolism and its risk factors in patients who received pdC1-INH with those who did not receive pdC1-INH as well as with those treated with danazol or with tranexamic acid. RESULTS: During the observation period (29 years), 104 of the 144 subjects received pdC1-INH. The average dose per treatment was 573.59 IU. None of the patients used an indwelling central venous catheter. Multiple risk factors for thromboembolism were identified in 93 of the 104 patients treated with pdC1-INH. The incidence rate of thromboembolism was 0.0019/100 person-years in patients treated with pdC1-INH, whereas it was 0.0211/100 person-years in the not-treated group. CONCLUSION: Our cohort study did not find any evidence for an increased risk of thromboembolism during treatment with pdC1-INH, despite the presence of multiple predisposing factors. PMID- 26802390 TI - 7th Edition NRP Brings Big Changes for NRP Instructors. PMID- 26802391 TI - Pulse Oximetry Screening for Critical Congenital Heart Defects. AB - Critical congenital heart defects (CCHD) are a subset of congenital heart defects that require acute diagnosis and interventions in order to provide optimal health outcomes for newborns. The incidence of infants with CCHD may be as high as six per 1,000 live births. Pulse oximetry screening is a new tool used in many nurseries to detect the presence of CCHD with high reliability. This article includes an overview of CCHD and the pulse oximetry screen, including the primary and secondary targets, a test algorithm, reliability, cost-effectiveness, limitations, national recommendations, and implications for nurses, particularly their role in the NICU. PMID- 26802392 TI - Review and Critical Analysis of Massage Studies for Term and Preterm Infants. AB - PURPOSE: To review and analyze studies evaluating the effects of massage on term and preterm infants. DESIGN: A systematic review of literature. RESULTS: Benefits of massage for term infants are: improved weight gain, growth, and sleep and decreased hyperbilirubinemia. Benefits for preterm infants are: improved weight gain, decreased response to pain, and increased interactions with parents. However, the few studies use different interventions related to timing and number of massages, and the outcomes vary among studies. There is not enough evidence to support the use of massage for term and preterm infants, but massage may be considered on a case-by-case basis. PMID- 26802393 TI - Another Preemie with Hypoglycemia? Beckwith-Wiedemann Syndrome--A Case Study. AB - Beckwith-Wiedemann syndrome (BWS) is the most common overgrowth disorder in infants. This article reviews a case of a premature infant with an atypical presentation of Beckwith-Wiedemann that was diagnosed at one month of age. It also addresses notable aspects of the etiology, diagnosis, and management of infants with BWS. PMID- 26802394 TI - Extracorporeal Membrane Oxygenation in the NICU. AB - Extracorporeal membrane oxygenation (ECMO) was developed for adults but has been used in neonates as a life-saving rescue therapy for infants with respiratory failure and/or cardiac collapse as a result of congenital diaphragmatic hernia, meconium aspiration syndrome, persistent pulmonary hypertension, or systemic sepsis. ECMO has been proven to increase the survival rate for these diseases. This article provides an overview of neonatal ECMO: the history and development of neonatal ECMO, patient selection criteria, clinical management, the ECMO circuit, weaning from ECMO, and possible complications of ECMO. PMID- 26802395 TI - An Innovative Strategy to Improve Family-Infant Bonding. AB - To improve family-infant bonding while newborns were separated from their parents, work began to develop a new Childbirth Center policy to guide staff in using Apple's FaceTime application with patients. Multidisciplinary meetings were held to obtain consent for the use of FaceTime and to protect patient information. We acquired two iPads and the support needed for updates. The staff was educated, and implementation began in January, 2014. This program improved bonding as evidenced by feedback received from the parents who utilized it. Several parents commented on how much they preferred seeing images of their babies in motion breathing and crying instead of just still pictures. Physicians also used FaceTime while talking with parents about plans of care. Since our implementation, we have utilized FaceTime with 46 infants to impact bonding in our Special Care nursery. This process enhances the delivery of relationship based care with our patients. PMID- 26802396 TI - Breastfeeding Success Is More Than Just Putting Baby to Breast. AB - Breastfeeding success in our society focuses heavily on putting the baby to the breast. However, NICU mothers and especially preemie moms struggle with this very task and are often feeling pressure from various angles medically and therapeutically. At the end of the day, it is about helping that mother build her confidence in her role in the NICU that can dictate breastfeeding success in whatever form that might take. PMID- 26802398 TI - News of the Academy of Neonatal Nursing. PMID- 26802419 TI - Of God and Psychotherapy. AB - Psychotherapy is an instrument for remediation of psychological deficits and conflict resolution, as well as an instrument for growth and self-cultivation. In fact, psychotherapy is the finest form of life education. All of this is done without psychotherapists' playing a teacher, a minister, a priest, a rabbi, an imam, or a Buddhist monk, but by being familiar with what they know and more. That "more" is about understanding "the attributes" of gods and religions as they serve the all-too-human needs of believing and belonging. It is about the distillation of common psychological, sociological, moral, and philosophical attributes of religions, and the recognition that the attributes themselves are faith and God. Attributes that serve the affiliative needs define faith, for example, belonging is faith; attributes that serve the divine needs define God, for example, compassion is God. Those who have recovered from their primitive innocence need to formulate their ideas of God and religion, regardless of their affiliation with a religious community. One may need to resonate emotionally with the God of his or her religion, but intellectually need to transcend all its dogma and cultivate a personal concept of divinity free from any theological structure. Such an enlightened person achieves enduring equanimity by striving to own the attributes of Gods--to be godly. This is equally true for psychotherapists as it is for their patients. PMID- 26802420 TI - Abnormal Grief: Should We Consider a More Patient-Centered Approach? AB - Grief, the psychological reaction to the loss of a significant other, varies complexly in its cause, experience, evolution, and prognosis. Although most bereaved individuals experience a normal grieving process, some develop complicated grief (CG) or major depressive disorder (MDD). The DSM-5, which controversially altered the nosology, recognizes grief-related major depression (GRMD) as a diagnostic subtype if a patient meets MDD criteria two weeks post bereavement. The (DSM-5) tries to distinguish between grief and MDD, but remains a symptom-based, centered approach to grief that is not patient centered. This article reviews grief in its normal and abnormal dimensions. Using an illustrative clinical case in which interpersonal psychotherapy (IPT) was employed, we discuss the need for a more patient-centered approach to treating abnormal grief, considering the patient's personal history, perceptions, experiences of bereavement, and interpersonal environment. Clinical studies need to better identify subgroups of individuals susceptible to abnormal grief and to evaluate their response to early interventions. PMID- 26802421 TI - Patients' Self-presentational Tactics as Predictors of the Early Therapeutic Alliance. AB - OBJECTIVES: The early therapeutic alliance is an important predictor for therapy outcome. However, knowledge about predictors of the therapeutic alliance is still limited. We examined if patients' self-presentational behaviors can predict the early therapeutic alliance. METHOD: Videotaped intake interviews of 60 randomly selected patients were coded for patients' self-presentational tactics. The therapeutic alliance was measured with the Bern Post-Session Report. RESULTS: From the therapists' perspective, Agenda setting and Self-promotion were positively related and Supplication was negatively related to the therapeutic alliance. From the patients' perspective, Agenda setting was negatively related and Self-promotion was positively related to the therapeutic alliance. Provoking a response from the therapist was unrelated to the therapeutic alliance as judged from both therapist and patient perspectives. Correlations were of small-to moderate size. These findings have important implications for building a constructive therapeutic alliance and identifying patients' needs. CONCLUSIONS: Patients' self-presentational behavior is a promising predictor of the early therapeutic alliance. PMID- 26802422 TI - Examining Our Tears: Therapists' Accounts of Crying in Therapy. AB - OBJECTIVES: The majority of psychologists experience therapist crying in therapy (TCIT). This study aimed to determine typical clinical contexts for, and psychologists' experiences of, TCIT. METHOD: Data was examined from 411 psychologists' and psychology trainees' accounts of their most recent TCIT experience. RESULTS: TCIT occurred with a diverse group of clients and happened throughout treatment. In 55% of accounts, therapists believed that their client was aware of TCIT. In 73%, the client was crying during TCIT. The most common emotion felt by the therapist was sadness. The most common session content for TCIT was grief. Data regarding therapists' experience of their tears and how they handled TCIT are presented. CONCLUSIONS: Therapists who discuss their TCIT with clients tended to report improvement in rapport. Suggestions are offered for clinicians regarding how to work with TCIT in therapy sessions. PMID- 26802423 TI - The Major Mobilization of the Unconscious and the Total Removal of Resistance in Davanloo's Intensive Short-term Dynamic Psychotherapy Part I: An Introduction. AB - Davanloo's Intensive Short-term Dynamic Psychotherapy has been the subject of various reviews. Davanloo has published extensively on his early work, but there have been no publications on his most recent work-most notably his Montreal Closed-circuit training program. This program focuses on his most recent discoveries and techniques and is a unique, videotaped supervisory program. It focuses on self-assessment and peer-assessment. It is also a unique format in which to review Davanloo's theoretical conceptions of resistance and the transference component of the resistance. This paper will review the early work of Davanloo as well as his most recent research findings. A case from the Montreal Closed-circuit training program will be reviewed in detail to highlight these findings. PMID- 26802424 TI - The Major Mobilization of the Unconscious and the Total Removal of Resistance in Davanloo's Intensive Short-term Dynamic Psychotherapy Part II: Treating the Transference Neurosis. AB - Davanloo's Intensive Short-term Dynamic Psychotherapy has been the subject of various reviews. The first article in this series focused on a review of Davanloo's early work as well as a discussion of some of his most recent research findings. A case from the Montreal closed circuit training program was reviewed. This second article will focus on Davanloo's views on the transference neurosis and how its development should be avoided at all costs. There will be further exploration of the case presented in Part I from the Montreal closed circuit training program. There will also be a special focus on detecting the transference neurosis when present and the technical interventions needed to lay the foundations for removing it. PMID- 26802427 TI - Early Weightbearing After Operatively Treated Ankle Fractures: A Biomechanical Analysis. AB - BACKGROUND: No consensus exists regarding the timing of weightbearing after surgical fixation of unstable traumatic ankle fractures. We evaluated fracture displacement and timing of displacement with simulated early weightbearing in a cadaveric model. METHODS: Twenty-four fresh-frozen lower extremities were assigned to Group 1, bimalleolar ankle fracture (n=6); Group 2, trimalleolar ankle fracture with unfixed small posterior malleolar fracture (n=9); or Group 3, trimalleolar ankle fracture with fixed large posterior malleolar fracture (n=9) and tested with axial compressive load at 3 Hz from 0 to 1000 N for 250 000 cycles to simulate 5 weeks of full weightbearing. Displacement was measured by differential variable reluctance transducer. RESULTS: The average motion at all fracture sites in all groups was significantly less than 1 mm (P < .05). Group 1 displacement of the lateral and medial malleolus fracture was 0.1+/-0.1 mm and 0.4+/-0.4 mm, respectively. Group 2 displacement of the lateral, medial, and posterior malleolar fracture was 0.6+/-0.4 mm, 0.5+/-0.4 mm, and 0.5+/-0.6 mm, respectively. Group 3 displacement of the lateral, medial, and posterior malleolar fracture was 0.1+/-0.1 mm, 0.5+/-0.7 mm, and 0.5+/-0.4 mm, respectively. The majority of displacement (64.0% to 92.3%) occurred in the first 50 000 cycles. There was no correlation between fracture displacement and bone mineral density. CONCLUSION: No significant fracture displacement, no hardware failure, and no new fractures occurred in a cadaveric model of early weightbearing in unstable ankle fracture after open reduction and internal fixation. CLINICAL RELEVANCE: This study supports further investigation of early weightbearing postoperative protocols after fixation of unstable ankle fractures. PMID- 26802428 TI - The Internet for Patient Education: A Friend or Foe? PMID- 26802429 TI - Genome Sequence and Analysis of Escherichia coli MRE600, a Colicinogenic, Nonmotile Strain that Lacks RNase I and the Type I Methyltransferase, EcoKI. AB - Escherichia coli strain MRE600 was originally identified for its low RNase I activity and has therefore been widely adopted by the biomedical research community as a preferred source for the expression and purification of transfer RNAs and ribosomes. Despite its widespread use, surprisingly little information about its genome or genetic content exists. Here, we present the first de novo assembly and description of the MRE600 genome and epigenome. To provide context to these studies of MRE600, we include comparative analyses with E. coli K-12 MG1655 (K12). Pacific Biosciences Single Molecule, Real-Time sequencing reads were assembled into one large chromosome (4.83 Mb) and three smaller plasmids (89.1, 56.9, and 7.1 kb). Interestingly, the 7.1-kb plasmid possesses genes encoding a colicin E1 protein and its associated immunity protein. The MRE600 genome has a G + C content of 50.8% and contains a total of 5,181 genes, including 4,913 protein-encoding genes and 268 RNA genes. We identified 41,469 modified DNA bases (0.83% of total) and found that MRE600 lacks the gene for type I methyltransferase, EcoKI. Phylogenetic, taxonomic, and genetic analyses demonstrate that MRE600 is a divergent E. coli strain that displays features of the closely related genus, Shigella. Nevertheless, comparative analyses between MRE600 and E. coli K12 show that these two strains exhibit nearly identical ribosomal proteins, ribosomal RNAs, and highly homologous tRNA species. Substantiating prior suggestions that MRE600 lacks RNase I activity, the RNase I encoding gene, rna, contains a single premature stop codon early in its open reading frame. PMID- 26802430 TI - Network-Based Analysis of eQTL Data to Prioritize Driver Mutations. AB - In clonal systems, interpreting driver genes in terms of molecular networks helps understanding how these drivers elicit an adaptive phenotype. Obtaining such a network-based understanding depends on the correct identification of driver genes. In clonal systems, independent evolved lines can acquire a similar adaptive phenotype by affecting the same molecular pathways, a phenomenon referred to as parallelism at the molecular pathway level. This implies that successful driver identification depends on interpreting mutated genes in terms of molecular networks. Driver identification and obtaining a network-based understanding of the adaptive phenotype are thus confounded problems that ideally should be solved simultaneously. In this study, a network-based eQTL method is presented that solves both the driver identification and the network-based interpretation problem. As input the method uses coupled genotype-expression phenotype data (eQTL data) of independently evolved lines with similar adaptive phenotypes and an organism-specific genome-wide interaction network. The search for mutational consistency at pathway level is defined as a subnetwork inference problem, which consists of inferring a subnetwork from the genome-wide interaction network that best connects the genes containing mutations to differentially expressed genes. Based on their connectivity with the differentially expressed genes, mutated genes are prioritized as driver genes. Based on semisynthetic data and two publicly available data sets, we illustrate the potential of the network-based eQTL method to prioritize driver genes and to gain insights in the molecular mechanisms underlying an adaptive phenotype. The method is available at http://bioinformatics.intec.ugent.be/phenetic_eqtl/index.html. PMID- 26802431 TI - The diagnostic value of two commercially available human cTnI assays in goat kids with myocarditis. AB - BACKGROUND: Cardiac troponin I (cTnI) is a peripheral blood marker for myocardial damage. Because of the unavailability of goat-specific cTnI assays human cTnI assays may be validated for detection of myocarditis in goat kids. OBJECTIVES: The purpose of the study was to evaluate 2 commercially available human cTnI assays in goat kids with myocardial damage, and to determine the cTnI expression in cardiac muscle. MATERIALS AND METHODS: Plasma cTnI concentrations were measured in healthy goat kids (n = 7) and goat kids with myocardial damage (n = 8) using the Beckman Coulter Access Accu TnI and the Biomerieux Vidas Ultra. The results were correlated with gross necropsy and histopathologic findings, and cTnI immunhistochemistry in cardiac tissue. RESULTS: Macro- and microscopic findings confirmed myocardial damage in the myocarditis group. Mean plasma cTnI concentration was significantly higher in the myocarditis group than in the healthy control group (104.82 vs 0.02 ng/mL). The overall mean plasma cTnI concentration measured by Biomerieux Vidas Ultra (61.75 ng/mL, 95% CI: 19.55 103.95) was comparable to the mean measured by Beckman Coulter Access Accu TnI (50.08 ng/mL, 95% CI: 24.11-76.06), and cTnI concentrations measured by these assays were highly correlated (r = .977) with a -6.2% bias. Both assays were precise and accurate. CONCLUSION: The human-specific Beckman Coulter Access Accu TnI and the Biomerieux Vidas Ultra can be used for diagnostic confirmation of myocardial damage in caprine medicine. PMID- 26802432 TI - Aberrant splicing of the DMP1-ARF-MDM2-p53 pathway in cancer. AB - Alternative splicing (AS) of mRNA precursors is a ubiquitous mechanism for generating numerous transcripts with different activities from one genomic locus in mammalian cells. The gene products from a single locus can thus have similar, dominant-negative or even opposing functions. Aberrant AS has been found in cancer to express proteins that promote cell growth, local invasion and metastasis. This review will focus on the aberrant splicing of tumor suppressor/oncogenes that belong to the DMP1-ARF-MDM2-p53 pathway. Our recent study shows that the DMP1 locus generates both tumor-suppressive DMP1alpha (p53 dependent) and oncogenic DMP1beta (p53-independent) splice variants, and the DMP1beta/alpha ratio increases with neoplastic transformation of breast epithelial cells. This process is associated with high DMP1beta protein expression and shorter survival of breast cancer (BC) patients. Accumulating pieces of evidence show that ARF is frequently inactivated by aberrant splicing in human cancers, demonstrating its involvement in human malignancies. Splice variants from the MDM2 locus promote cell growth in culture and accelerate tumorigenesis in vivo. Human cancers expressing these splice variants are associated with advanced stage/metastasis, and thus have negative clinical impacts. Although they lack most of the p53-binding domain, their activities are mostly dependent on p53 since they bind to wild-type MDM2. The p53 locus produces splice isoforms that have either favorable (beta/gamma at the C-terminus) or negative impact (Delta40, Delta133 at the N-terminus) on patients' survival. As the oncogenic AS products from these loci are expressed only in cancer cells, they may eventually become targets for molecular therapies. PMID- 26802433 TI - External Validation of the Manchester Acute Coronary Syndromes Decision Rule. AB - OBJECTIVES: The Manchester Acute Coronary Syndromes (MACS) decision rule has been shown to be a powerful diagnostic tool in emergency department (ED) patients with suspected acute coronary syndromes (ACS). It has the potential to improve system efficiency by identifying patients suitable for discharge after a single blood draw for high-sensitivity troponin and heart-type fatty acid-binding protein (h FABP) analysis at presentation to the ED. The objective was to externally validate the MACS decision rule and establish its diagnostic accuracy as a discharge tool in a new set of prospectively recruited ED patients. METHODS: In this preplanned analysis of a prospectively recruited single-center cohort, consecutive ED patients >=18 years with suspected ACS were included. Testing for h-FABP and high-sensitivity troponin T was undertaken on serum drawn on arrival, and any clinical features required to calculate the MACS rule were recorded. The primary outcome was major adverse cardiac events (MACE) within 30 days (acute myocardial infarction [AMI], death, or revascularization). The secondary outcome was AMI alone, adjudicated using 6-hour troponin results. RESULTS: Of the 782 participants included, 78 (10.0%) developed MACE and 61 (7.8%) had an AMI. Of participants, 133 (17.0%) were identified as "very low risk" and therefore suitable for immediate discharge with a 0% incidence of MACE or AMI. Of remaining patients, 314 (40.2%) were "low risk," 320 (40.9%) were "moderate risk," and 15 (1.9%) were "high risk," with incidences of MACE of 2.2, 19.7, and 53.3%, respectively. The sensitivity was 100% (95% confidence interval [CI] = 95.4% to 100%) for MACE at 30 days and 100% (95% CI = 94.1% to 100%) for AMI. The area under the receiver operating characteristic curve was 0.87 (95% CI = 0.83 to 0.91) for the MACS rule in the prediction of MACE. CONCLUSIONS: In this prospectively recruited cohort of ED patients with suspected ACS, the MACS decision rule identifies a significant proportion of patients who are suitable for immediate discharge after a single blood draw at presentation, with a very low risk of MACE at 30 days. This study externally validates previous findings that the MACS rule is a powerful diagnostic tool in this setting. A randomized controlled trial to establish the utility of the rule in an everyday clinical setting is justified. PMID- 26802434 TI - Personalized medicine in diabetes: the role of 'omics' and biomarkers. AB - Personalized medicine, otherwise called stratified or precision medicine, aims to better target intervention to the individual to maximize benefit and minimize harm. This review discusses how diabetes aetiology, pathophysiology and patient genotype influence response to or side effects of the commonly used diabetes treatments. C-peptide is a useful biomarker that is underused to guide treatment choice, severe insulin deficiency predicts non-response to glucagon-like peptide 1 receptor agonists, and thiazolidinediones are more effective in insulin resistant patients. The field of pharmacogenetics is now yielding clinically important results, with three examples outlined: sulphonylurea sensitivity in patients with HNF1A maturity-onset diabetes of the young; sulphonylurea sensitivity in patients with Type 2 diabetes with reduced function alleles at CYP2C9, resulting in reduced metabolism of sulphonylureas; and severe metformin intolerance associated with reduced function organic cation transporter 1 (OCT1) variants, exacerbated by drugs that also inhibit OCT1. Genome-wide approaches and the potential of other 'omics', including metagenomics and metabolomics, are then outlined, highlighting the complex interacting networks that we need to understand before we can truly personalize diabetes treatments. PMID- 26802436 TI - Guidelines for managing diabetes in Ramadan. AB - BACKGROUND: Globally there are approximately 90 million Muslims with diabetes of which approximately 400 000 reside within the UK. The holy month of Ramadan is a fundamental practice of this religion of which fasting from sun-rise to sun-set is an integral part. This poses many potential risks for those with diabetes who wish to observe Ramadan. METHODS: The evidence base for best clinical management of Type 1 and Type 2 diabetes during Ramadan was reviewed. We reviewed current and previous recommendations for safe fasting during Ramadan. RESULTS: The risks associated with fasting in those with diabetes and preparing your patient for Ramadan are discussed. We have reviewed the evidence around diet-controlled diabetes and therapies including; metformin, acarbose, metglitinides, sulfonylureas, thiazolidinidiones, dipeptidyl peptidase-4 inhibitor (DPP-4), sodium glucose co-transporter -2 (SGLT-2) inhibitors, glucagon-like peptide -1 (GLP-1) receptor agonists and insulin. CONCLUSION: Up to date guidelines for the management of treatment regimes are set-out for those with Type 1 and Type 2 diabetes who wish to fast during Ramadan. PMID- 26802437 TI - NPYFa, A Chimeric Peptide of Met-Enkephalin, and NPFF Induces Tolerance-Free Analgesia. AB - Methionine-enkephalin-Arg-Phe is an endogenous amphiactive analgesic peptide. Neuropeptide FF, on the other hand, is reported for its role in opioid modulation and tolerance development. Based on these reports, in the present study we designed a chimeric peptide NPYFa (YGGFMKKKPQRFamide), having the Met-enkephalin (opioid) and PQRFamide sequence of neuropeptide FF, which can then target both the opioid and neuropeptide FF receptors. We hypothesized that the chimeric peptide so designed would have both analgesic properties and further aid in understanding of the role of neuropeptide FF in the development of opiate tolerance. Our studies indicated that NPYFa induced an early onset, potent, dose dependent and prolonged antinociception. Additionally, antagonists (MOR, KOR, and DOR) pretreatment studies determined a KOR-mediated antinociception activity of the ligand. Further, in vitro binding studies using the Eu-GTP-gammaS binding assay on cell lines expressing opioid and NPFF receptors showed binding to both the opioid and neuropeptide FF receptors suggesting a multiple receptor binding character of NPYFa. Moreover, chronic (6 days) treatment with NPYFa exhibited an absence of tolerance development subsequent to its analgesia. The current study proposes NPYFa as a potent, long-acting antinociceptor lacking tolerance development as well as a probe to study opioid analgesia and the associated complex mechanisms of tolerance development. PMID- 26802435 TI - Hypothalamic Wnt Signalling and its Role in Energy Balance Regulation. AB - Wnt signalling and its downstream effectors are well known for their roles in embryogenesis and tumourigenesis, including the regulation of cell proliferation, survival and differentiation. In the nervous system, Wnt signalling has been described mainly during embryonic development, although accumulating evidence suggests that it also plays a major role in adult brain morphogenesis and function. Studies have predominantly concentrated on memory formation in the hippocampus, although recent data indicate that Wnt signalling is also critical for neuroendocrine control of the developed hypothalamus, a brain centre that is key in energy balance regulation and whose dysfunction is implicated in metabolic disorders such as type 2 diabetes and obesity. Based on scattered findings that report the presence of Wnt molecules in the tanycytes and ependymal cells lining the third ventricle and arcuate nucleus neurones of the hypothalamus, their potential importance in key regions of food intake and body weight regulation has been investigated in recent studies. The present review brings together current knowledge on Wnt signalling in the hypothalamus of adult animals and discusses the evidence suggesting a key role for members of the Wnt signalling family in glucose and energy balance regulation in the hypothalamus in diet-induced and genetically obese (leptin deficient) mice. Aspects of Wnt signalling in seasonal (photoperiod sensitive) rodents are also highlighted, given the recent evidence indicating that the Wnt pathway in the hypothalamus is not only regulated by diet and leptin, but also by photoperiod in seasonal animals, which is connected to natural adaptive changes in food intake and body weight. Thus, Wnt signalling appears to be critical as a modulator for normal functioning of the physiological state in the healthy adult brain, and is also crucial for normal glucose and energy homeostasis where its dysregulation can lead to a range of metabolic disorders. PMID- 26802438 TI - Adult-onset respiratory insufficiency, scoliosis, and distal joint hyperlaxity in patients with multiminicore disease due to novel Megf10 mutations. AB - INTRODUCTION: Multiminicore disease is a congenital myopathy characterized pathologically by the presence of multiple minicore structures in the sarcoplasm. Mutations in the selenoprotein N1-encoding gene (SEPN1) and ryanodine receptor 1 encoding gene (RYR1) are responsible for half of the reported cases. Mutations in multiple epidermal growth factor-like domains 10-encoding gene (MEGF10) have been identified only recently in a few patients with antenatal to infantile-onset myopathy, with and without minicore pathology. METHODS: We report 2 sisters with adult-onset respiratory insufficiency followed by development of limb weakness. Both had scoliosis, distal joint hyperlaxity, and high-arched feet. RESULTS: A biopsy of the right triceps muscle in 1 sister showed multiple minicore structures. She had electromyographic changes of myopathy with fibrillation potentials and myotonic discharges. Next generation sequencing identified novel compound heterozygous missense variants in MEGF10 c.230G>A (p.Arg77Gln) and c.1833T>G (p.Cys611Trp) in both sisters. CONCLUSIONS: MEGF10 mutations can cause myopathy with adult-onset respiratory insufficiency. Muscle Nerve, 2016 Muscle Nerve 53: 984-988, 2016. PMID- 26802439 TI - Molecular cloning and expression of toll-like receptor 4 (tlr4) in the blunt snout bream (Megalobrama amblycephala). AB - Toll-like receptors (TLRs) play a pivotal role in teleost innate immune system. In this study, Megalobrama amblycephala (ma) tlr4 gene was cloned, its putative polypeptide product characterized, and expression analysed. Matlr4 cDNA is 2862 bp long, with an open reading frame of 2364 bp encoding 787 amino acids. MaTlr4 is a typical TLR protein, including the extracellular part with nine leucine-rich repeat motifs, a transmembrane region and a cytoplasmic Toll/interleukin-1 receptor domain. MaTlr4 has the highest level of identity (94%) and similarity (97%) with the grass carp Tlr4.2 homolog. This was also corroborated by the phylogenetic analysis, which placed MaTlr4 in a cluster with other cyprinid homologs. Matlr4 mRNA was ubiquitously expressed in all examined tissues and during all sampled developmental stages. The observed peak in matlr4 mRNA expression during gastrula and somite stages is in good agreement with its proposed role in the development of the neural system. Temporal expression patterns of matlr4 and maMyD88 mRNAs and proteins were analyzed in liver, spleen, head kidney, trunk kidney and intestine after Aeromonas hydrophila infection. And mRNA expression varied between different time-points. Both MaTlr4 and MaMyD88 protein expressions at 12 hpi were significantly enhanced in head kidney and intestine. These results indicate that matlr4 is involved in the immune response in M. amblycephala, and that it is indeed a functional homologue of tlr4s described in other animal species. PMID- 26802440 TI - Cell-laden hydrogel/titanium microhybrids: Site-specific cell delivery to metallic implants for improved integration. AB - Porous titanium implants are widely used in dental, orthopaedic and otorhinolaryngology fields to improve implant integration to host tissue. A possible step further to improve the integration with the host is the incorporation of autologous cells in porous titanium structures via cell-laden hydrogels. Fast gelling hydrogels have advantageous properties for in situ applications such as localisation of specific cells and growth factors at a target area without dispersion. The ability to control the cell types in different regions of an implant is important in applications where the target tissue (i) has structural heterogeneity (multiple cell types with a defined spatial configuration with respect to each other); (ii) has physical property gradients essential for its function (such as in the case of osteochondral tissue transition). Due to their near immediate gelation, such gels can also be used for site-specific modification of porous titanium structures, particularly for implants which would face different tissues at different locations. Herein, we describe a step by step design of a model system: the model cell-laden gel containing porous titanium implants in the form of titanium microbead/hydrogel (maleimide-dextran or maleimide-PVA based) microhybrids. These systems enable the determination of the effect of titanium presence on gel properties and encapsulated cell behaviour as a miniaturized version of full-scale implants, providing a system compatible with conventional analysis methods. We used a fibroblast/vascular endothelial cell co-cultures as our model system and by utilising single microbeads we have quantified the effect of gel microenvironment (degradability, presence of RGD peptides within gel formulation) on cell behaviour and the effect of the titanium presence on cell behaviour and gel formation. Titanium presence slightly changed gel properties without hindering gel formation or affecting cell viability. Cells showed a preference to move towards the titanium beads and fibroblast proliferation was significantly higher in hybrids compared to gel only controls. The MMP (Matrix Metalloproteinase) sensitive hydrogels induced sprouting by cells in co-culture configuration which was quantified by fluorescence microscopy, confocal microscopy and qRT-PCR (Quantitative Reverse transcription polymerase chain reaction). When the microhybrid up-scaled to 3D thick structures, cellular localisation in specific areas of the 3D titanium structures was achieved, without decreasing overall cell proliferation compared to titanium only scaffolds. Microhybrids of titanium and hydrogels are useful models for deciding the necessary modifications of metallic implants and they can be used as a modelling system for the study of tissue/titanium implant interactions. STATEMENT OF SIGNIFICANCE: This article demonstrates a method to apply cell-laden hydrogels to porous titanium implants and a model of titanium/hydrogel interaction at micro-level using titanium microbeads. The feasibility of site-specific modification of titanium implants with cell-laden microgels has been demonstrated. Use of titanium microbeads in combination with hydrogels with conventional analysis techniques as described in the article can facilitate the characterisation of surface modification of titanium in a relevant model system. PMID- 26802441 TI - Influence of pore size of porous titanium fabricated by vacuum diffusion bonding of titanium meshes on cell penetration and bone ingrowth. AB - The present work assesses the potential of three-dimensional (3D) porous titanium (pore size of 188-390 MUm and porosity of 70%) fabricated by vacuum diffusion bonding of titanium meshes for applications in bone engineering. Rat bone marrow mesenchymal stem cells were used to investigate the proliferation and differentiation of cells on titanium scaffolds with different pore sizes at day 7, day 14 and day 21 based on DNA contents, alkaline phosphatase (ALP) activity, collagen (COL) secretion and osteogenic gene expressions including ALP, COL-1, bone morphogenetic protein-2 (BMP-2), osteopontin (OPN), runt-related transcription factor 2 (RUNX2), using smooth solid titanium plate as reference material. The rabbit models with distal femoral condyles defect were used to investigate the bone ingrowth into the porous titanium. All samples were subjected to Micro-CT and histological analysis after 4 and 12 weeks of healing. A one-way ANOVA followed by Tukey post hoc tests was used to analyze the data. It was found that the differentiation stage of cells on the porous titanium delayed compared with the smooth solid titanium plate and Ti 188 was more inclined to promote cell differentiation at the initial stage (day 14) while cell proliferation (day 1, 4, 7, 10, 14 and 21) and bone ingrowth (4 and 12 weeks) were biased to Ti 313 and Ti 390. The study indicates that the hybrid porous implant design which combines the advantages of different pore sizes may be meaningful and promising for bone defect restoration. STATEMENT OF SIGNIFICANCE: One of the significant challenges in bone defect restoration is the integration of biomaterials and surrounding bone tissue. Porous titanium may be a promising choice for bone ingrowth and mineralization with appropriate mechanical and biological properties. In this study, based on porous titanium fabricated by vacuum diffusion bonding of titanium meshes, we have evaluated the influence of various pore sizes on rat bone marrow mesenchymal stem cells (rBMMSCs) penetration in vitro and bone ingrowth in vivo. It was interesting that we found the proliferation and differentiation abilities of rBMMSCs, as well as bone ingrowth were related to different pore sizes of such porous scaffolds. The results may provide guidance for porous titanium design for bone defect restoration. PMID- 26802442 TI - Induction of mesenchymal stem cell chondrogenic differentiation and functional cartilage microtissue formation for in vivo cartilage regeneration by cartilage extracellular matrix-derived particles. AB - We propose a method of preparing a novel cell carrier derived from natural cartilage extracellular matrix (ECM), designated cartilage ECM-derived particles (CEDPs). Through a series of processes involving pulverization, sieving, and decellularization, fresh cartilage was made into CEDPs with a median diameter of 263 +/- 48 MUm. Under microgravity culture conditions in a rotary cell culture system (RCCS), bone marrow stromal cells (BMSCs) can proliferate rapidly on the surface of CEDPs with high viability. Histological evaluation and gene expression analysis indicated that BMSCs were differentiated into mature chondrocytes after 21 days of culture without the use of exogenous growth factors. Functional cartilage microtissue aggregates of BMSC-laden CEDPs formed as time in culture increased. Further, the microtissue aggregates were directly implanted into trochlear cartilage defects in a rat model (CEDP+MSC group). Gait analysis and histological results indicated that the CEDP+MSC group obtained better and more rapid joint function recovery and superior cartilage repair compared to the control groups, in which defects were treated with CEDPs alone or only fibrin glue, at both 6 and 12 weeks after surgery. In conclusion, the innovative cell carrier derived from cartilage ECM could promote chondrogenic differentiation of BMSCs, and the direct use of functional cartilage microtissue facilitated cartilage regeneration. This strategy for cell culture, stem cell differentiation and one-step surgery using cartilage microtissue for cartilage repair provides novel prospects for cartilage tissue engineering and may have further broad clinical applications. STATEMENT OF SIGNIFICANCE: We proposed a method to prepare a novel cell carrier derived from natural cartilage ECM, termed cartilage ECM derived particles (CEDPs), which can support proliferation of MSCs and facilitate their chondrogenic differentiation. Further, the direct use of functional cartilage microtissue of MSC-laden CEDP aggregates for cartilage repair in vivo induced hyaline-like articular cartilage repair. This strategy for cell culture, stem cell differentiation and the one-step surgery for cartilage repair provide novel prospects for cartilage tissue engineering and may have further broad clinical applications. PMID- 26802443 TI - Magnetic induction heating of superparamagnetic nanoparticles during rewarming augments the recovery of hUCM-MSCs cryopreserved by vitrification. AB - Cryopreservation by vitrification has been recognized as a promising strategy for long-term banking of living cells. However, the difficulty to generate a fast enough heating rate to minimize devitrification and recrystallization-induced intracellular ice formation during rewarming is one of the major obstacles to successful vitrification. We propose to overcome this hurdle by utilizing magnetic induction heating (MIH) of magnetic nanoparticles to enhance rewarming. In this study, superparamagnetic (SPM) Fe3O4 nanoparticles were synthesized by a chemical coprecipitation method. We successfully applied the MIH of Fe3O4 nanoparticles for rewarming human umbilical cord matrix mesenchymal stem cells (hUCM-MSCs) cryopreserved by vitrification. Our results show that extracellular Fe3O4 nanoparticles with MIH may efficiently suppress devitrification and/or recrystallization during rewarming and significantly improve the survival of vitrified cells. We further optimized the concentration of Fe3O4 nanoparticles and the current of an alternating current (AC) magnetic field for generating the MIH to maximize cell viability. Our results indicate that MIH in an AC magnetic field with 0.05% (w/v) Fe3O4 nanoparticles significantly facilitates rewarming and improves the cryopreservation outcome of hUCM-MSCs by vitrification. The application of MIH of SPM nanoparticles to achieve rapid and spatially homogeneous heating is a promising strategy for enhanced cryopreservation of stem cells by vitrification. STATEMENT OF SIGNIFICANCE: Here we report the successful synthesis and application of Fe3O4 nanoparticles for magnetic induction heating (MIH) to enhance rewarming of vitrification-cryopreserved human umbilical cord matrix mesenchymal stem cells (hUCM-MSCs). We found that MIH-enhanced rewarming greatly improves the survival of vitrification-cryopreserved hUCM-MSCs. Moreover, the hUCM-MSCs retain their intact stemness and multilineage potential of differentiation post cryopreservation by vitrification with the MIH-enhanced rewarming. Therefore, the novel MIH-enhanced cell vitrification is valuable to facilitate the long-term storage of hUCM-MSCs and possibly many other important cells to meet their ever-increasing demand by the burgeoning cell-based medicine. PMID- 26802444 TI - Small hydrophobe substitution on polyethylenimine for plasmid DNA delivery: Optimal substitution is critical for effective delivery. AB - Cationic polymers have been turned into effective gene delivery agents by functionalizing with long-chain aliphatic lipids, but little information exists if small hydrophobic moieties can serve as effective substituents for this purpose. To explore this issue, we modified small molecular weight (1.2kDa) polyethylenimine (1.2PEI) by a small hydrophobe, propionic acid (PrA), through N acylation and investigated the efficacy of resultant polymers to deliver plasmid DNA (pDNA) to breast cancer cells MDA-231 and MCF-7. A significant impact of PrA grafting was observed on physicochemical features of polymers and resultant pDNA complexes. pDNA binding capacity, as measured by BC50 (weight ratio for 50% binding), was decreased from 0.25 to 0.64 with PrA substitution. Hydrodynamic size of polymer/pDNA complexes was not altered, but the surface charge (xi potential) was increased with low PrA substitution and decreased at higher PrA substitutions. Similarly, in vitro pDNA transfection efficacy in MDA-231 and MCF 7 cells was significantly increased with PrA grafting and optimum efficacy was observed in polymers with modest substitution, 0.25-1.0 PrAs/PEI (mol/mol), but higher substitutions was detrimental to transfection. The transfection efficiency of PEI-PrAs was higher than aliphatic lipid (linoleic acid) substituted PEI and more stable than 25kDa branched PEI. However, unlike studies reported elsewhere, siRNA had no effect on transfection efficacy of pDNA/PEI-PrA complexes when used as an additive. We conclude that small hydrophobe substitution on low MW PEI converts it into effective pDNA delivery agent in breast cancer cells up to an optimal ratio, indicating that balancing hydrophobicity of polymer is critical for pDNA transfection. STATEMENT OF SIGNIFICANCE: This manuscript investigated the influence of small hydrophobe (propionic acid, PrA, 3 carbon) grafted onto small molecular weight polyethylenimine (1.2PEI) in pDNA delivery. We have explored this approach as an alternative of common strategies to graft long chain and/or bulky lipids [linoleic acid (18 carbon), cholesterol]. At optimal substitution, transfection efficiency of these polymers was significantly higher than long chain lipid substituted 1.2PEI, emphasizing a proper hydrophobic/hydrophilic balance for optimum gene delivery. The overall results establish the feasibility of using small hydrophobes to create functional carriers, as long as the polymers are engineered with optimal ratio of substituent. The reported studies should facilitate the efforts of biomaterials scientists and engineers to design new carriers for gene therapy. PMID- 26802445 TI - Health Education Research and Practice Literature on Hispanic Health Issues: Have We Lost Sight of the Largest Minority Population? AB - Hispanics constitute the largest racial/ethnic minority population in the United States and are the fastest growing segment of the population. Knowledge about health needs and practices, effective health promotion programs, and health policy making for Hispanics has the potential to improve population health outcomes for this group. Continued research and practice literature will aid in accomplishing these objectives. However, little is known about the extent of health education-related literature available on Hispanic health issues. In this review, we analyzed research and practice publications in all health education related journals to assess the volume of articles published on Hispanic health issues. We found that the portion of journal articles devoted to Hispanic health issues varied widely among the journals and that there was a very limited emphasis on Hispanic health-related issues. Journal editors and editorial board members may need to be more proactive in soliciting manuscripts on Hispanic health, and our practitioners may have to improve their professional skills and cultural competence in order to work with Hispanic populations to produce research and practice literature that is of adequate quantity and quality to help improve Hispanics' health. PMID- 26802446 TI - A fluorimetric binding assay for angiotensin II and kinin receptors. AB - Angiotensin II (AngII) and kinins (bradykinin (BK) and des-Arg9-bradykinin (DBK)), are potent agents involved in the maintenance of blood pressure and several biological activities, and their better understanding is important to produce new drugs aimed to control arterial blood pressure. Previous studies on ligand-receptor binding have been based on radioactive methods, which led us to study a new method based on the fluorimetric method. A lanthanide attached to the N-terminal segment of the peptide (AngII, BK and DBK), which produces a time resolved-fluorescent ligand, was used in a binding test with CHO cells expressing the AT1, AT2, B1 or B2 receptors in comparison with the same cell line tested with the radioactive ligand. Our findings indicated that the non-radioactive method provided a comparable result for the angiotensin receptors. On the other hand, the kinin receptors showed a slight reduction in the binding affinity, probably due to the linkage at the N-terminal segment and/or to the lower biological stability associated to the high temperature (37 degrees C) used for the fluorimetric method, while the radioactive one was at 4 degrees C. We can conclude that a time-resolved fluorescence assay would provide a sensitive method as an alternative tool for receptor studies. PMID- 26802448 TI - [The family physician in the university]. PMID- 26802449 TI - [Editorial]. PMID- 26802447 TI - The complexity of diagnosing latent tuberculosis infection in older adults in long-term care facilities. AB - OBJECTIVES: In the USA, tuberculosis disease rates are highest in older adults. Diagnostic testing for latent tuberculosis infection (LTBI) has not been evaluated carefully in this group. The aim of this study was to define the relationship between tuberculin skin test (TST) results, T-SPOT.TB results, and T cell responses to Mycobacterium tuberculosis antigens. METHODS: Long-term care facility residents with known prior TST results (positive or negative) were retested with TSTs and T-SPOT.TB. Prior exposure to M. tuberculosis was assessed by quantifying T-cell activation to mycobacterial antigens in vitro. RESULTS: The median age of the 37 participants was 77 years (range 57-98 years). Among 18 participants with a prior positive TST, three (16.7%) had a negative TST when retested (TST reversion); two had a negative T-SPOT.TB. Of the 15 who were historically and currently TST-positive, four (26.7%) had a negative T-SPOT.TB and one (6.7%) had a borderline result. Percentages of CD4+ T-cells responding to mycobacterial antigens were higher in participants with positive TST and T SPOT.TB (18.2%) compared to those with a positive TST but negative T-SPOT.TB (6.4%, p=0.16) and negative TST and T-SPOT.TB (5.9%, p<0.001). CONCLUSIONS: LTBI testing in older adults is complicated by TST reversion and TST-positive/T SPOT.TB-negative discordance, which may reflect clearance of infection or waning immunity. PMID- 26802450 TI - Neuroepidemiology: From science to medical practice. PMID- 26802451 TI - The contralateral delay activity as a neural measure of visual working memory. AB - The contralateral delay activity (CDA) is a negative slow wave sensitive to the number of objects maintained in visual working memory (VWM). In recent years, a growing number of labs started to use the CDA in order to investigate VWM, leading to many fascinating discoveries. Here, we discuss the recent developments and contribution of the CDA in various research fields. Importantly, we report two meta-analyses that unequivocally validate the relationship between the set size increase in the CDA amplitude and the individual VWM capacity, and between the CDA and filtering efficiency. We further discuss how the CDA was used to study the role of VWM in visual search, multiple object tracking, grouping, binding, and whether VWM capacity allocation is determined by the items' resolution or instead by the number of objects regardless of their complexity. In addition, we report how the CDA has been used to characterize specific VWM deficits in special populations. PMID- 26802452 TI - Necrostatin-1 rescues mice from lethal irradiation. AB - There is an emerging need in new medical products that can mitigate and/or treat the short- and long-term consequences of radiation exposure after a radiological or nuclear terroristic event. The direct effects of ionizing radiation are realized primarily via apoptotic death pathways in rapidly proliferating cells within the initial 1-2days after the exposure. However later in the course of the radiation disease necrotic cell death may ensue via direct and indirect pathways from increased generation of pro-inflammatory cytokines. Here we evaluated radiomitigative potential of necrostatin-1 after total body irradiation (TBI) and the contribution of necroptosis to cell death induced by radiation. Circulating TNFalpha levels were increased starting on d1 after TBI and associated with increased plasmalemma permeability in ileum of irradiated mice. Necrostatin-1 given iv. 48h after 9.5Gy TBI attenuated radiation-induced receptor interacting protein kinase 3 (RIPK3) serine phosphorylation in ileum and improved survival vs. vehicle. Utilizing apoptosis resistant cytochrome c(-/-) cells, we showed that radiation can induce necroptosis, which is attenuated by RNAi knock down of RIPK1 and RIPK3 or by treatment with necrostatin-1 or -1s whereas 1-methyl-L tryptophan, an indoleamine-2,3-dioxygenase inhibitor, did not exhibit radiomitigative effect. This suggests that the beneficial effect of necrostatin-1 is likely through inhibition of RIPK1-mediated necroptotic pathway. Overall, our data indicate that necroptosis, a form of programmed necrosis, may play a significant role in cell death contributing to radiation disease and mortality. This study provides a proof of principle that necrostatin-1 and perhaps other RIPK1 inhibitors are promising therapeutic agents for radiomitigation after TBI. PMID- 26802453 TI - A light-dark shift strategy derived from light-responded metabolic behaviors for polyketides production in marine fungus Halorosellinia sp. AB - Light, as an important environmental signal, generally brings about a broad regulation in fungal metabolism. In this work, we aim to explore the light responded metabolic rules so as to further develop a feasible and effective light regulation strategy for production of anticancer polyketide 1403C by marine fungus Halorosellinia sp.. Light derived production enhancement of polyketides was first found in shake flask. To further understand this well working black box, light-responded cell growth, polyketides biosynthesis, metabolic behaviors (enzymes activities and organic acids levels) and mycelia morphology were then investigated in 5-L bioreactor. By comparing cultures under constant irradiation and dark conditions, the entire bioprocess was divided into two phases. During 0 60h, light presumably stimulated relevant metabolism to generate sufficient energy, NADPH and carbon skeleton, particularly malonyl-CoA, which was favorable for mycelia growth and polyketides accumulation. After 60h, light did harm to biomass and polyketides production. Consequently, a light-dark shift strategy was proposed and verified in 5-L bioreactor. It led to a maximal 1403C production of 1.67g/L, which was 24% and 74% higher than those obtained under constant irradiation and dark conditions, respectively. PMID- 26802454 TI - Comparison between dot-immunoblotting assay and clinical sign determination method for quantifying avian infectious bronchitis virus vaccine by titration in embryonated eggs. AB - A sensitive and specific method for measuring the vaccine titer of infectious bronchitis virus (IBV) is important to commercial manufacturers for improving vaccine quality. Typically, IBV is titrated in embryonated chicken eggs, and the infectivity of the virus dilutions is determined by assessing clinical signs in the embryos as evidence of viral propagation. In this study, we used a dot immunoblotting assay (DIA) to measure the titers of IBV vaccines that originated from different pathogenic strains or attenuation methods in embryonated eggs, and we compared this assay to the currently used method, clinical sign evaluation. To compare the two methods, we used real-time reverse transcription-PCR, which had the lowest limit of detection for propagated IBV. As a clinical sign of infection, dwarfism of the embryo was quantified using the embryo: egg (EE) index. The DIA showed 9.41% higher sensitivity and 15.5% higher specificity than the clinical sign determination method. The DIA was particularly useful for measuring the titer of IBV vaccine that did not cause apparent stunting but propagated in embryonated chicken eggs such as a heat-adapted vaccine strain. The results of this study indicate that the DIA is a rapid, sensitive, reliable method for determining IBV vaccine titer in embryonated eggs at a relatively low cost. PMID- 26802455 TI - Idiopathic thoracic epidural lipomatosis presenting with back pain. PMID- 26802456 TI - Solitary plasmacytoma of the thoracic spine. PMID- 26802457 TI - Aggressive vertebral hemangioma of the thoracic spine. PMID- 26802458 TI - Breast cancer presenting with intramedullary cervical spinal cord metastasis. PMID- 26802459 TI - Genetic characterization of Toxoplasma gondii from autopsy proven cases of AIDS associated cerebral toxoplasmosis in South India. AB - Toxoplasma gondii (T.gondii) infection can be devastating in the immunodeficient causing high morbidity and mortality. Due to limited availability of both diagnostic facilities and Highly Active Antiretroviral Therapy (HAART), toxoplasmosis continues to be a significant problem amongst Acquired Immuno Deficiency Syndrome (AIDS) patients in India. While scanty literature is available on T. gondii isolates in animals in India, little is known about the genetic diversity of the parasite in humans. Therefore, the present study investigated the genetic diversity of T. gondii in 25 confirmed cases of cerebral toxoplasmosis developing on the background of human immunodeficiency virus (HIV) infection/AIDS. PCR DNA sequencing was performed at four important genetic loci of T. gondii: BTUB, GRA6, alternative SAG2 (alt SAG2) and SAG3 on DNA from tissues obtained at postmortem. The amplified products from all the cases were successfully sequenced except at one locus for one case. Results of the present study suggest that majority of the patients (22/25; 88%) in South India are infected with strains that are recombinants of type II/III and/or strains representing T. gondii different from the archetypal lineages I, II, and III. In addition, clonal types III, MAS, and MAS variant genotypes were encountered. No clonal type I or II was seen in the present study. In addition, variants were observed at alt SAG2 and SAG3 but BTUB and GRA6 were highly conserved. Single nucleotide polymorphisms were observed mainly at two loci which are coding for surface antigens at alt SAG2 and SAG3. In conclusion, the present study reveals genetic diversity in India amongst strains of T. gondii from clinical cases of toxoplasmosis which is in accordance with other recent studies showing a high rate of genetic diversity in this parasite across the globe. There is a need to genotype T. gondii from different forms of toxoplasmosis in humans in India. PMID- 26802461 TI - Greater diversification of freshwater than marine parasites of fish. AB - The species richness of freshwater environments is disproportionately high compared with that of the oceans, given their respective sizes. If diversification rates are higher in freshwaters because they are isolated and heterogeneous, this should apply to parasites as well. Using 14 large datasets comprising 677 species of freshwater and marine fish, the hypothesis that freshwater parasites experience higher rates of diversification than marine ones is tested by contrasting the relative numbers of species per parasite genus between the regional endohelminth faunas of fish in both environments. The relationship between the number of parasite genera and the number of parasite species per host was well described by a power function, in both environments; although the exponent of this function was slightly lower for freshwater parasite faunas than marine ones, the difference was not significant. However, the ratio between the number of parasite species and the number of parasite genera per host species was significantly higher in freshwater fish than in marine ones. These findings suggest fundamental differences between the way parasite faunas diversify in freshwater versus marine habitats, with the independent evolution of conspecific parasite populations in isolated host populations being a more common phenomenon in freshwater environments. PMID- 26802460 TI - What to do with high autofluorescence background in pancreatic tissues - an efficient Sudan black B quenching method for specific immunofluorescence labelling. AB - AIMS: High levels of autofluorescence in tissue samples can entirely mask specific labellings with fluorophores and thus impair immunofluorescence histochemistry. In pancreatic tissue samples we observed autofluorescence as a common problem often mediated by the fixation and processing procedure. METHODS AND RESULTS: Using epifluorescence microscopy, we analysed the intensity and spatial distribution of autofluorescence in formalin-fixed, paraffin-embedded human pancreatic tissues and developed an efficient quenching method to reduce the unwanted light emission. The optimized quenching protocol using Sudan black B reduced the unequally distributed tissue autofluorescence to a low and intensity equalized background level. Quantitative image analysis demonstrated autofluorescence suppression by 65-95%, depending on the selected fluorescence filter setups. The procedure did not affect specific immunofluorescence labelling or tissue integrity. As a clear result of Sudan black B treatment, a tremendous improvement of the signal-to-noise ratio was achieved, allowing a reliable detection and quantification of specific fluorescent labels. Other tissue treatment methods, such as cupric sulphate, toluidine blue and ultraviolet irradiation, or combinations of these with Sudan black B, were not as efficient. CONCLUSIONS: The easy-to-perform Sudan black B technique improves dramatically qualitative and quantitative fluorescence analysis of critical pancreatic tissue sections and rescues even overfixed tissues for immunofluorescence application. PMID- 26802462 TI - L-Arginine ethylester enhances in vitro amplification of PrP(Sc) in macaques with atypical L-type bovine spongiform encephalopathy and enables presymptomatic detection of PrP(Sc) in the bodily fluids. AB - Protease-resistant, misfolded isoforms (PrP(Sc)) of a normal cellular prion protein (PrP(C)) in the bodily fluids, including blood, urine, and saliva, are expected to be useful diagnostic markers of prion diseases, and nonhuman primate models are suited for performing valid diagnostic tests for human Creutzfeldt Jakob disease (CJD). We developed an effective amplification method for PrP(Sc) derived from macaques infected with the atypical L-type bovine spongiform encephalopathy (L-BSE) prion by using mouse brain homogenate as a substrate in the presence of polyanions and L-arginine ethylester. This method was highly sensitive and detected PrP(Sc) in infected brain homogenate diluted up to 10(10) by sequential amplification. This method in combination with PrP(Sc) precipitation by sodium phosphotungstic acid is capable of amplifying very small amounts of PrP(Sc) contained in the cerebrospinal fluid (CSF), saliva, urine, and plasma of macaques that have been intracerebrally inoculated with the L-BSE prion. Furthermore, PrP(Sc) was detectable in the saliva or urine samples as well as CSF samples obtained at the preclinical phases of the disease. Thus, our novel method may be useful for furthering the understanding of bodily fluid leakage of PrP(Sc) in nonhuman primate models. PMID- 26802463 TI - Developmental changes in hepatic glucose metabolism in a newborn piglet model: A comparative analysis for suckling period and early weaning period. AB - The liver glucose metabolism, supplying sufficient energy for glucose-dependent tissues, is important in suckling or weaned animals, although there are few studies with piglet model. To better understand the development of glucose metabolism in the piglets during suckling period and early weaning period, we determined the hepatic glycogen content, and investigated the relative protein expression of key enzymes of glucogenesis (GNG) and mRNA levels of some glucose metabolism-related genes. During suckling period, the protein level of G6Pase in the liver of suckling piglets progressively declined with day of age compared with that of newborn piglets (at 1 day of age), whereas the PEPCK level stabilized until day 21 of age, indicating that hepatic GNG capacity gradually weakened in suckling piglets. The synthesis of hepatic glycogen, which was consistent with the fluctuation of glycolytic key genes PFKL and PKLR that gradually decreased after birth and was more or less steady during latter suckling period, although both the mRNA levels of GCK and key glucose transporter GLUT2 presented uptrend in suckling piglets. However, early weaning significantly suppressed the hepatic GNG in the weaned piglets, especially at d 3-5 of weaning period, then gradually recovered at d 7 of weaning period. Meanwhile, PFKL, PKLR and GLUT2 showed the similar trend during weaning period. On the contrast, the hepatic glycogen reached the maximum value when the G6Pase and PEPCK protein expression were at the lowest level, although the GCK level maintained increasing through 7 days of weaning period. Altogether, our study provides evidence that hepatic GNG and glycolysis in newborn piglets were more active than other days during suckling period, and early weaning could significantly suppressed glucose metabolism in liver, but this inhibition would progressively recover at day 7 after weaning. PMID- 26802464 TI - Effects of mechanical stress and vitreous samples in retinal pigment epithelial cells. AB - In rhegmatogenous retinal detachment (RRD), scattered RPE cells from the basement membrane into the vitreous cavity undergo an epithelial mesenchymal transition (EMT) and form the intraocular fibrous membrane in response to vitreous fluid. We investigated whether exposure to vitreous samples was associated with EMT associated signals and mesenchymal characters. Human vitreous samples were collected from patients with RRD, epiretinal membrane (ERM), or macular hole (MH). We evaluated the effects of vitreous on ARPE-19 cells in suspension cultures using poly 2-hydroxyethyl methacrylate-coated dishes and three dimensional (3D) Matrigel cultures. We found that exposure to vitreous samples did not induce morphological changes or accelerate wound closure in monolayers. Several samples showed increased phosphorylation of Smad2 and nuclear translocation of nuclear factor-kappaB. Mechanical stress triggered an elevation of phosphorylation levels in Smad2. In addition, exposure to vitreous fluid increased the phosphorylation of p38 mitogen-activated protein kinase in cell suspension cultures after mechanical stress. Moreover, ARPE-19 cells showed a stellate invasive phenotype in 3D Matrigel cultures with vitreous samples. In this study, we demonstrated that mechanical stress and vitreous were associated with EMT-associated signals and invasive phenotypes in 3D cultures but not in monolayers. These results have important implications for the role of vitreous humor in the induction of EMT and intraocular fibrosis. PMID- 26802465 TI - Characterization of Cimex lectularius (bedbug) defensin peptide and its antimicrobial activity against human skin microflora. AB - Antimicrobial peptides are components of both vertebrate and invertebrate innate immune systems that are expressed in response to exposure to bacterial antigens. Naturally occurring antimicrobial peptides from evolutionarily ancient species have been extensively studied and are being developed as potential therapeutics against antibiotic resistant microorganisms. In this study, a putative Cimex lectularius (bedbug, CL) defensin is characterized for its effectiveness against human skin flora including Gram-negative and Gram-positive bacteria. The bedbug defensin (CL-defensin), belonging to family of insect defensins, is predicted to have a characteristic N-terminal loop, an alpha-helix, and an antiparallel beta sheet, which was supported by circular dichroism spectroscopy. The defensin was shown to be antimicrobial against Gram-positive bacteria commonly found on human skin (Micrococcus luteus, Corynebacterium renale, Staphylococcus aureus and Staphylococcus epidermidis); however, it was ineffective against common skin Gram negative bacteria (Pseudomonas aeruginosa and Acinetobacter baumannii) under low salt conditions. CL-defensin was also effective against M. luteus and C. renale in high-salt (MIC) conditions. Our studies indicate that CL-defensin functions by depolarization and pore-formation in the bacterial cytoplasmic membrane. PMID- 26802466 TI - Reactive oxygen species regulatory mechanisms associated with rapid response of MC3T3-E1 cells for vibration stress. AB - Although many previous studies have shown that refractory period-dependent memory effect of vibration stress is anabolic for skeletal homeostasis, little is known about the rapid response of osteoblasts simply derived from vibration itself. In view of the potential role of reactive oxygen species (ROS) in mediating differentiated activity of osteoblasts, whether and how ROS regulates the rapid effect of vibration deserve to be demonstrated. Our findings indicated that MC3T3 E1 cells underwent decreased gene expression of Runx2, Col-I and ALP and impaired ALP activity accompanied by increased mitochondrial fission immediately after vibration loading. Moreover, we also revealed the involvement of ERK-Drp1 signal transduction in ROS regulatory mechanisms responsible for the rapid effect of vibration stress. PMID- 26802467 TI - D-chiro-inositol glycan reduces food intake by regulating hypothalamic neuropeptide expression via AKT-FoxO1 pathway. AB - The regulation of food intake is important for body energy homeostasis. Hypothalamic insulin signaling decreases food intake by upregulating the expression of anorexigenic neuropeptides and downregulating the expression of orexigenic neuropeptides. INS-2, a Mn(2+) chelate of 4-O-(2-amino-2-deoxy-beta-D galactopyranosyl)-3-O-methyl-D-chiro-inositol, acts as an insulin mimetic and sensitizer. We found that intracerebroventricular injection of INS-2 decreased body weight and food intake in mice. In hypothalamic neuronal cell lines, INS-2 downregulated the expression of neuropeptide Y (NPY), an orexigenic neuropeptide, but upregulated the expression of proopiomelanocortin (POMC), an anorexigenic neuropeptide, via modulation of the AKT-forkhead box-containing protein-O1 (FoxO1) pathway. Pretreatment of these cells with INS-2 enhanced the action of insulin on downstream signaling, leading to a further decrease in NPY expression and increase in POMC expression. These data indicate that INS-2 reduces food intake by regulating the expression of the hypothalamic neuropeptide genes through the AKT-FoxO1 pathway downstream of insulin. PMID- 26802468 TI - Dipeptidyl peptidase-4 inhibitor MK-626 restores insulin secretion through enhancing autophagy in high fat diet-induced mice. AB - Autophagy is cellular machinery for maintenance of beta-cell function and mass. The current study aimed to investigate the regulatory effects of MK-626, a dipeptidyl peptidase-4 inhibitor, on insulin secretion through the activation of autophagy in high fat diet-induced obese mice. C57BL/6 mice were fed with a rodent diet containing 45 kcal% fat for 16 weeks to induce obesity and then were received either vehicle or MK-626 (3 mg/kg/day) orally during the final 4 weeks. Mouse islets were isolated. Phosphorylation of serine/threonine-protein kinase mTOR and levels of light chain 3B I (LC3B I), LC3B II, sequestosome-1 (SQSTM1/p62) and autophagy-related protein-7 (Atg7) were examined by Western blotting. Glucagon like-peptide-1 (GLP-1) level and insulin secretion were measured by ELISA. GLP-1 level in plasma was decreased in obese mice, which was elevated by dipeptidyl peptidase-4 inhibitor MK-626. In the islets of obese mice, phosphorylation of mTOR, ratio of LC3B I and LC3B II, and level of p62 were elevated and the expression of Atg7 and insulin secretion were reduced compared to those of C57BL/6 mice. However, such effects were reversed by MK-626. Autophagy activator rapamycin stimulated insulin secretion in obese mice but autophagy inhibitor chloroquine treatment inhibited insulin secretion in obese mice administrated by MK-626. Furthermore, the beneficial effects of MK-626 were inhibited by GLP-1 receptor antagonist exendin 9-39. The present study reveals the activation of autophagy to mediate the anti-diabetic effect of GLP-1. PMID- 26802470 TI - Icariin inhibits atherosclerosis progress in Apoe null mice by downregulating CX3CR1 in macrophage. AB - Horny Goat Weed is a commonly used in Chinese herbal medicine. And it is used in multiple kinds of diseases including cardiovascular diseases. Icariin is the major component isolated from Horny Goat Weed. It is reported to have lipid lowering effect. In atherosclerosis, icariin attenuate the enhanced prothrombotic state independently of its lipid-lowering effects. However, its detail mechanism is remaining unclear. This study aimed to investigate the effect and mechanism of icariin on atherosclerosis. We performed gene expression profiling on icariin treated LPS-stimulated RAW264.7 and its control cells. Microarray analyses identified a list of genes significantly differentially expressed after icariin treated including downregulation of CX3CR1. Apoe null mice were assigned into 3 groups: control group, diet with 30 mg/kg/d icariin and diet with 60 mg/kg/d icariin. The results showed that icariin treatment significantly reduced lesion area and macrophage infiltration. Also icariin reduced CX3CR1 and CX3CL1 protein levels in the artery wall. In conclusion, icariin could be a potential anti atherosclerosis agent by downregulating the expression of CX3CR1. PMID- 26802469 TI - Renoprotective effect of DPP-4 inhibitors against free fatty acid-bound albumin induced renal proximal tubular cell injury. AB - Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. PMID- 26802471 TI - High-frequency profile in adolescents and its relationship with the use of personal stereo devices. AB - OBJECTIVE: To analyze and correlate the audiometric findings of high frequencies (9-16 kHz) in adolescents with their hearing habits and attitudes, in order to prevent noise-induced hearing loss. METHOD: This was a descriptive cross sectional study, which included 125 adolescents in a sample of normal-hearing students, at a state school. The subjects performed high-frequency audiometry testing and answered a self-administered questionnaire addressing information on sound habits concerning the use of personal stereo devices. The sample was divided according to the exposure characteristics (time, duration, intensity, etc.) and the results were compared with the observed thresholds, through the difference in proportions test, chi-squared, Student's t-test, and ANOVA, all at a significance level of 0.05. RESULTS: Average high-frequency thresholds were registered below 15 dB HL and no significant correlation was found between high frequency audiometric findings and the degree of exposure. CONCLUSION: The prevalence of harmful sound habits due to the use of personal stereo devices is high in the adolescent population, but there was no correlation between exposure to high sound pressure levels through personal stereos and the high-frequency thresholds in this population. PMID- 26802472 TI - Daytime urinary incontinence: a chronic and comorbid condition of childhood. PMID- 26802473 TI - Atypical manifestations of Epstein-Barr virus in children: a diagnostic challenge. AB - OBJECTIVE: Clarify the frequency and the pathophysiological mechanisms of the rare manifestations of Epstein-Barr virus infection. SOURCES: Original research studies published in English between 1985 and 2015 were selected through a computer-assisted literature search (PubMed and Scopus). Computer searches used combinations of key words relating to "EBV infections" and "atypical manifestation." SUMMARY OF THE FINDINGS: Epstein-Barr virus is a herpes virus responsible for a lifelong latent infection in almost every adult. The primary infection concerns mostly children and presents with the clinical syndrome of infectious mononucleosis. However, Epstein-Barr virus infection may exhibit numerous rare, atypical and threatening manifestations. It may cause secondary infections and various complications of the respiratory, cardiovascular, genitourinary, gastrointestinal, and nervous systems. Epstein-Barr virus also plays a significant role in pathogenesis of autoimmune diseases, allergies, and neoplasms, with Burkitt lymphoma as the main representative of the latter. The mechanisms of these manifestations are still unresolved. Therefore, the main suggestions are direct viral invasion and chronic immune response due to the reactivation of the latent state of the virus, or even various DNA mutations. CONCLUSIONS: Physicians should be cautious about uncommon presentations of the viral infection and consider EBV as a causative agent when they encounter similar clinical pictures. PMID- 26802474 TI - The sensitivity of laboratory tests assessing driving related skills to dose related impairment of alcohol: A literature review. AB - Laboratory tests assessing driving related skills can be useful as initial screening tools to assess potential drug induced impairment as part of a standardized behavioural assessment. Unfortunately, consensus about which laboratory tests should be included to reliably assess drug induced impairment has not yet been reached. The aim of the present review was to evaluate the sensitivity of laboratory tests to the dose dependent effects of alcohol, as a benchmark, on performance parameters. In total, 179 experimental studies were included. Results show that a cued go/no-go task and a divided attention test with primary tracking and secondary visual search were consistently sensitive to the impairing effects at medium and high blood alcohol concentrations. Driving performance assessed in a simulator was less sensitive to the effects of alcohol as compared to naturalistic, on-the-road driving. In conclusion, replicating results of several potentially useful tests and their predictive validity of actual driving impairment should deserve further research. In addition, driving simulators should be validated and compared head to head to naturalistic driving in order to increase construct validity. PMID- 26802475 TI - Meso and micro-scale response of post carbon removal nitrifying MBBR biofilm across carrier type and loading. AB - This study investigates the effects of three specific moving bed biofilm reactor (MBBR) carrier types and two surface area loading rates on biofilm thickness, morphology and bacterial community structure of post carbon removal nitrifying MBBR systems along with the effects of carrier type and loading on ammonia removal rates and effluent solids settleability. The meso and micro analyses show that the AOB kinetics vary based on loading condition, but irrespective of carrier type. The meso-scale response to increases in loading was shown to be an increase in biofilm thickness with higher surface area carriers being more inclined to develop and maintain thicker biofilms. The pore spaces of these higher surface area to volume carriers also demonstrated the potential to become clogged at higher loading conditions. Although the biofilm thickness increased during higher loading conditions, the relative percentages of both the embedded viable and non-viable cells at high and conventional loading conditions remained stable; indicating that the reduced ammonia removal kinetics observed during carrier clogging events is likely due to the observed reduction in the surface area of the attached biofilm. Microbial community analyses demonstrated that the dominant ammonia oxidizing bacteria for all carriers is Nitrosomonas while the dominant nitrite oxidizing bacteria is Nitrospira. The research showed that filamentous species were abundant under high loading conditions, which likely resulted in the observed reduction in effluent solids settleability at high loading conditions as opposed to conventional loading conditions. Although the settleability of the effluent solids was correlated to increases in abundances of filamentous organisms in the biofilm, analyzed using next generation sequencing, the ammonia removal rate was not shown to be directly correlated to specific meso or micro-scale characteristics. Instead post carbon removal MBBR ammonia removal kinetics were shown to be related to the viable AOB cell coverage of the carriers; which was calculated by normalizing the surface area removal rate by the biofilm thickness, the bacterial percent abundance of ammonia oxidizing bacteria and the percentage of viable cells. PMID- 26802476 TI - Investigating the stability of gadolinium based contrast agents towards UV radiation. AB - Since the 1980s, the broad application of gadolinium(Gd)-based contrast agents for magnetic resonance imaging (MRI) has led to significantly increased concentrations of Gd in the aqueous environment. Little is known about the stability of these highly polar xenobiotics under environmental conditions, in wastewater and in drinking water treatment. Therefore, the stability of frequently applied Gd-based MRI contrast agents towards UV radiation was investigated. The hyphenation of hydrophilic interaction liquid chromatography (HILIC) with inductively coupled plasma mass spectrometry (ICP-MS) and of HILIC with electrospray ionization mass spectrometry (ESI-MS) provided quantitative elemental information as well as structural information. The contrast agents Gd DTPA, Gd-DOTA and Gd-BT-DO3A showed a high stability in irradiation experiments applying a wavelength range from 220 nm to 500 nm. Nevertheless, the degradation of Gd-BOPTA as well as the formation of Gd-containing transformation products was observed by means of HILIC-ICP-MS. Matrix-dependent irradiation experiments showed a degradation of Gd-BOPTA down to 3% of the initial amount in purified water after 300 min, whereas the degradation was slowed down in drinking water and surface water. Furthermore, it was observed that the sum of species continuously decreased with proceeding irradiation in all matrices. After irradiation in purified water for 300 min only 16% of the sum of species was left. This indicates a release of Gd(III) ions from the complex in course of irradiation. HILIC-ESI-MS measurements revealed that the transformation products mostly resulted from O-dealkylation and N-dealkylation reactions. In good correlation with retention times, the majority of transformation products were found to be more polar than Gd-BOPTA itself. Based on accurate masses, sum formulas were obtained and structures could be proposed. PMID- 26802477 TI - When's dinner? Does timing of dinner affect the cardiometabolic risk profiles of South-Asian Canadians at risk for diabetes. AB - AIM: To explore the relationship between the time dinner is consumed (dinnertime or timing of dinner) and cardiometabolic risk factors among South-Asian Canadians at risk for diabetes. METHODS: We recruited 432 South-Asian adults affiliated with Sikh and Hindu Temples in Metro Vancouver. Participants deemed to be at risk of diabetes underwent a clinical and behavioural assessment. Dinnertime was measured via self-report. Clinical endpoints included HbA1c , apolipoprotein, blood pressure, weight, BMI and waist circumference. RESULTS: The mean age of participants was 65 years and 59% were male. Dinnertime was categorized into three groups: early (before 18:00 h); average (18:00 to 20:00 h); and late (later than 20:00 h). Among the participants, 19% (n = 79), 44% (n = 187) and 37% (n = 157) reported early, average and late dinnertimes, respectively. Significant differences were found for dinnertime groups and years of residence in Canada, gender and employment. Compared with the early dinnertime group, the late dinnertime group lived in Canada for a shorter duration, comprised a higher proportion of males (66 vs 48%; P = 0.01) and were currently employed (37 vs 22%; P = 0.02). With regard to clinical endpoints, compared with the early dinnertime group, the late dinnertime group had lower systolic blood pressure (135.9 vs 131.7 mmHg; P = 0.03). After controlling for demographic characteristics, this difference was diminished. No significant differences were found between dinnertime and HbA1c , apolipoprotein, diastolic blood pressure, weight, BMI and waist circumference. CONCLUSION: Findings suggest that, among this sample of South-Asian Canadians at risk of Type 2 diabetes, there was no association between timing of the evening meal and cardiometabolic profiles. PMID- 26802478 TI - Twin pregnancies complicated by gestational diabetes mellitus: a single centre cohort study. AB - AIMS: In women with a twin pregnancy, to determine the incidence of, risk factors for and outcomes of women with gestational diabetes mellitus, and assess how these have changed with a change in gestational diabetes screening. METHODS: Retrospective cohort study of women with a twin pregnancy attending an Australian tertiary hospital, 2002-2013. Information on gestational diabetes status, gestational diabetes risk factors and pregnancy outcomes was ascertained. Pregnancy outcomes included hypertensive disorders, twin birthweight centile and a composite adverse pregnancy outcome. Analysis was stratified pre/post screening protocol change (epoch 1: 2002-2009, epoch 2: 2010-2013) and by gestational diabetes status. RESULTS: Gestational diabetes was diagnosed in 86/982 (8.8%) women, increasing from 4.4% to 14.7% between epochs (P = 0.0001). The proportion of women with hypertensive disorders increased (11.7% vs. 13.4%, P = 0.009), but the proportion of infant's birthweight > 90th centile decreased (11.0% vs. 7.6%, P = 0.02) between epochs. Overall, 33.6% of women had >= 1 risk factors for gestational diabetes. Three-quarters (73.7%) of women overall had an adverse pregnancy outcome, with a slightly higher proportion in women with gestational diabetes compared with those with no gestational diabetes (79.7% vs. 73.1%, P = 0.06). The rate of the adverse pregnancy outcome did not change by epoch, after adjusting for maternal and pregnancy risk factors (adjusted odds ratio = 0.96, 95% confidence interval 0.73-1.26). CONCLUSIONS: Almost 1 in 10 women with a twin pregnancy were diagnosed with gestational diabetes, with the incidence of gestational diabetes increasing threefold with a new screening protocol. The pregnancy outcomes of women with a twin pregnancy did not change with increased detection and treatment for gestational diabetes. PMID- 26802479 TI - Evolutionary escape on complex genotype-phenotype networks. AB - We study the problem of evolutionary escape that is the process whereby a population under sudden changes in the selective pressures acting upon it try to evade extinction by evolving from previously well-adapted phenotypes to those that are favoured by the new selective pressure. We perform a comparative analysis between results obtained by modelling genotype space as a regular hypercube (H-graphs), which is the scenario considered in previous work on the subject, to those corresponding to a complex genotype-phenotype network (B graphs). In order to analyse the properties of the escape process on both these graphs, we apply a general theory based on multi-type branching processes to compute the evolutionary dynamics and probability of escape. We show that the distribution of distances between phenotypes in B-graphs exhibits a much larger degree of heterogeneity than in H-graphs. This property, one of the main structural differences between both types of graphs, causes heterogeneous behaviour in all results associated to the escape problem. We further show that, due to the heterogeneity characterising escape on B-graphs, escape probability can be underestimated by assuming a regular hypercube genotype network, even if we compare phenotypes at the same distance in H-graphs. Similarly, it appears that the complex structure of B-graphs slows down the rate of escape. PMID- 26802480 TI - A spatio-temporal model for spontaneous thrombus formation in cerebral aneurysms. AB - We propose a new numerical model to describe thrombus formation in cerebral aneurysms. This model combines CFD simulations with a set of bio-mechanical processes identified as being the most important to describe the phenomena at a large space and time scales. The hypotheses of the model are based on in vitro experiments and clinical observations. We document that we can reproduce very well the shape and volume of patient specific thrombus segmented in giant aneurysms. PMID- 26802482 TI - Repopulation dynamics of single haematopoietic stem cells in mouse transplantation experiments: Importance of stem cell composition in competitor cells. AB - The transplantation of blood tissues from bone marrow into a lethally irradiated animal is an experimental procedure that is used to study how the blood system is reconstituted by haematopoietic stem cells (HSC). In a competitive repopulation experiment, a lethally irradiated mouse was transplanted with a single HSC as a test cell together with a number of bone marrow cells as competitor cells, and the fraction of the test cell progeny (percentage of chimerism) was traced over time. In this paper, we studied the stem cell kinetics in this experimental procedure. The balance between symmetric self-renewal and differentiation divisions in HSC determined the number of cells which HSC produce and the length of time for which HSC live after transplantation. The percentage of chimerism depended on the type of test cell (long-, intermediate-, or short-term HSC), as well as the type and number of HSC included in competitor cells. We next examined two alternative HSC differentiation models, one-step and multi-step differentiation models. Although these models differed in blood cell production, the percentage of chimerism appeared very similar. We also estimated the numbers of different types of HSC in competitor cells. Based on these results, we concluded that the experimental results inevitably include stochasticity with regard to the number and the type of HSC in competitor cells, and that, in order to detect different types of HSC, an appropriate number of competitor cells needs to be used in transplantation experiments. PMID- 26802481 TI - Influences of Allee effects in the spreading of malignant tumours. AB - A recent study by Korolev et al. [Nat. Rev. Cancer, 14:371-379, 2014] evidences that the Allee effect-in its strong form, the requirement of a minimum density for cell growth-is important in the spreading of cancerous tumours. We present one of the first mathematical models of tumour invasion that incorporates the Allee effect. Based on analysis of the existence of travelling wave solutions to this model, we argue that it is an improvement on previous models of its kind. We show that, with the strong Allee effect, the model admits biologically relevant travelling wave solutions, with well-defined edges. Furthermore, we uncover an experimentally observed biphasic relationship between the invasion speed of the tumour and the background extracellular matrix density. PMID- 26802483 TI - Culturomics as a data playground for tests of selection: Mathematical approaches to detecting selection in word use. AB - In biological evolution traits may rise and fall in frequency due to genetic drift, where variant frequencies change by chance, or by selection where advantageous variants will rise in frequency. The neutral model of evolution, first developed by Kimura in the 1960s, has become the standard against which selection is detected. While the balance between these two important forces - drift and selection - has been well established in biology there are other domains where the contribution of these processes is still coming together. Although the idea of natural selection has been applied to the cultural domain since the time of Darwin, it has proven more challenging to positively identify cultural traits under selection both because of a lack of established tests for selection and a lack of large cultural data sets. However, in recent years with the accumulation of large cultural data sets many cultural features from pre history pottery to modern baby names have been shown to evolve according to the neutral theory. But there is accumulating empirical evidence from cultural processes suggesting that the neutral theory alone cannot account for all features of the data. As such, there has been a renewed interest in determining whether there is selection amidst drift. Here we analyze a subset English word frequencies, and determine whether frequency change reveals processes of selection. Inspired by the Moran and Wright-Fisher models in population genetics, we developed a neutral model of word frequency variation to assess when linguistic data appears to depart from neutral evolution. As such, our model represents a possible "test for selection" in the linguistic domain. We explore how the distribution of word use has changed for sets of words in English for more than 100 years (1901-2008) as expressed in vocabulary usage in published books, made available by Google Ngram. When comparing empirical word frequency changes to our neutral model we find pervasive and systematic departures from neutrality. PMID- 26802484 TI - A Simplified model of mutually inhibitory sleep-active and wake-active neuronal populations employing a noise-based switching mechanism. AB - Infant rats switch randomly between the sleeping and waking states; during early infancy (up to postnatal day 8), sleep and wake bouts are random, brief (with means on the order of several seconds) and exponentially distributed, with the length of a particular bout independent of the length of prior bouts. As the rat ages during this early period, mean sleep and wake bout lengths gradually increase, though sleep and wake bouts remain exponentially distributed. Additionally, sleep and wake bouts are regulated independently of each other - alterations in the development of sleep (wake) bouts has no impact on the regulation wake (sleep) bouts. Sleep and wake bout behavior is associated with the activity of mutually inhibitory sleep-active and wake-active brainstem populations. In this work, I employ a simplified biophysical model of two mutually inhibitory populations consisting of ten integrate-and-fire neurons each and a noise-based switching mechanism. I show that such a noise-based switching mechanism naturally accounts for the experimentally observed features of sleep wake switching during early infancy - random alternating activity bouts occur as a consequence of noise (provided inhibition is strong relative to excitation), bout durations are exponential (due to a lack of memory within the system), and cross-population inhibition or intrapopulation excitatory coupling provide mechanisms for changing and independently regulated sleep and wake bout means. PMID- 26802485 TI - Pre-treatment SNOT-22 score predicts response to Endoscopic Polypectomy in Clinic (EPIC) our experience in 30 adults. PMID- 26802486 TI - Fires in storages of LFO: Analysis of hazard of structural collapse of steel aluminium containers. AB - Pool fires of light fuel oil (LFO) in above-ground storages with steel-aluminium containers are discussed. A model is developed for assessments of risks of between-tank fire spread. Radiative effects of the flame body are accounted for by a solid flame radiation model. Thermal profiles evolved due to fire in the adjacent tanks and their consequential structural response is pursued in an exact (materially and geometrically non-linear) manner. The model's derivation is demonstrated on the LFO tank storage located near the Port of Koper (Slovenia). In support of the model, data from literature are adopted where appropriate. Analytical expressions are derived correspondingly for calculations of emissive characteristics of LFO pool fires. Additional data are collected from experiments. Fire experiments conducted on 300cm diameter LFO pans and at different wind speeds and high-temperature uniaxial tension tests of the analysed aluminium alloys types 3xxx and 6xxx are presented. The model is of an immediate fire engineering practical value (risk analyses) or can be used for further research purposes (e.g. sensitivity and parametric studies). The latter use is demonstrated in the final part of the paper discussing possible effects of high temperature creep of 3xxx aluminium. PMID- 26802487 TI - Nano and microcarriers to improve stem cell behaviour for neuroregenerative medicine strategies: Application to Huntington's disease. AB - The potential treatments for neurodegenerative disorders will be revolutionized by the transplantation of stem cells or neuronal progenitors derived from these cells. It is however crucial to better monitor their proliferation, improve their survival and differentiation and hence ameliorate their engraftment after transplantation. To direct stem cell fate, a delicate control of gene expression through RNA interference (RNAi) is emerging as a safe epigenetic approach. The development of novel biomaterials (nano and microcarriers) capable of delivering proteins, nucleic acids and cells, open the possibility to regulate cell fate while achieving neuroprotection and neurorepair and could be applied to Huntington's disease. This review first provides an overview of stem cell therapy for the neurodegenerative disorder Huntington's disease. Within that context, an integrative discussion follows of the control of stem cell behaviour by RNAi delivered by different nanocarriers in vitro prior to their transplantation. Finally, combined in vivo strategies using stem cells, biomaterials and epigenetic cell regulation are reported. PMID- 26802488 TI - Cysticercosis/taeniasis endemicity in Southeast Asia: Current status and control measures. AB - The parasitic zoonoses cysticercosis/taeniasis is among the 17 major Neglected Tropical Diseases (NTDs) identified by the WHO as a focus for research and control. It is caused by a larval stage (cysticercus) infection of Taenia solium tapeworm in both humans and pigs. Cysticercosis occurs in many resource-poor countries, especially those with warm and mild climates in the regions of Latin America (LA), Asia and Sub-Saharan Africa (SSA). The prevalence of human cysticercosis is marked in those areas where individuals are traditionally keen to consume raw or insufficiently cooked pork and/or where the husbandry of pigs is improper. The worldwide burden of cysticercosis is unclear and notably, large scale control initiatives are lacking in all regions. This review focuses on the current endemic status of cysticercosis caused by T. solium infection in both humans and pigs living in 13 Southeast Asian countries. We will also emphasize epidemiological data as well as prevention and control of human neurocysticercosis. PMID- 26802489 TI - Estimation of the health and economic burden of neurocysticercosis in India. AB - Taenia solium is an endemic parasite in India which occurs in two forms in humans: cysticercosis (infection of soft tissues) and taeniosis (intestinal infection). Neurocysticercosis (NCC) is the most severe form of cysticercosis in which cysts develop in the central nervous system. This study was conducted to estimate health and economic impact due to human NCC-associated active epilepsy in India. Input data were sourced from published research literature, census data and other official records. Economic losses due to NCC-associated active epilepsy were estimated based on cost of treatment, hospitalisation and severe injury as well as loss of income. The disability-adjusted life years (DALYs) due to NCC were estimated by combining years of life lost due to early death and the number of years compromised due to disability taking the disease incidence into account. DALYs were estimated for five age groups, two genders and four regions, and then combined. To account for uncertainty, probability distributions were used for disease incidence data and other input parameters. In addition, sensitivity analyses were conducted to determine the impact of certain input parameters on health and economic estimates. It was estimated that in 2011, human NCC associated active epilepsy caused an annual median loss of Rupees 12.03 billion (uncertainty interval [95% UI] Rs. 9.16-15.57 billion; US $ 185.14 million) with losses of Rs. 9.78 billion (95% UI Rs. 7.24-13.0 billion; US $ 150.56 million) from the North and Rs. 2.22 billion (95% UI Rs. 1.58-3.06 billion; US $ 34.14 million) from the South. The disease resulted in a total of 2.10 million (95% UI 0.99-4.10 million) DALYs per annum without age weighting and time discounting with 1.81 million (95% UI 0.84-3.57 million) DALYs from the North and 0.28 million (95% UI 0.13-0.55 million) from the South. The health burden per thousand persons per year was 1.73 DALYs (95% UI 0.82-3.39). The results indicate that human NCC causes significant health and economic impact in India. Programs for controlling the disease should be initiated to reduce the socio-economic impact of the disease in India. PMID- 26802490 TI - A more appropriate white blood cell count for estimating malaria parasite density in Plasmodium vivax patients in northeastern Myanmar. AB - The conventional method of estimating parasite densities employ an assumption of 8000 white blood cells (WBCs)/MUl. However, due to leucopenia in malaria patients, this number appears to overestimate parasite densities. In this study, we assessed the accuracy of parasite density estimated using this assumed WBC count in eastern Myanmar, where Plasmodium vivax has become increasingly prevalent. From 256 patients with uncomplicated P. vivax malaria, we estimated parasite density and counted WBCs by using an automated blood cell counter. It was found that WBC counts were not significantly different between patients of different gender, axillary temperature, and body mass index levels, whereas they were significantly different between age groups of patients and the time points of measurement. The median parasite densities calculated with the actual WBC counts (1903/MUl) and the assumed WBC count of 8000/MUl (2570/MUl) were significantly different. We demonstrated that using the assumed WBC count of 8000 cells/MUl to estimate parasite densities of P. vivax malaria patients in this area would lead to an overestimation. For P. vivax patients aged five years and older, an assumed WBC count of 5500/MUl best estimated parasite densities. This study provides more realistic assumed WBC counts for estimating parasite densities in P. vivax patients from low-endemicity areas of Southeast Asia. PMID- 26802491 TI - Identification of genes involved in pyrethroid-, propoxur-, and dichlorvos- insecticides resistance in the mosquitoes, Culex pipiens complex (Diptera: Culicidae). AB - Culex pipiens pallens and Cx. p. quinquefasciatus are important vectors of many diseases, such as West Nile fever and lymphatic filariasis. The widespread use of insecticides to control these disease vectors and other insect pests has led to insecticide resistance becoming common in these species. In this study, high throughout Illumina sequencing was used to identify hundreds of Cx. p. pallens and Cx. p. quinquefasciatus genes that were differentially expressed in response to insecticide exposure. The identification of these genes is a vital first step for more detailed investigation of the molecular mechanisms involved in insecticide resistance in Culex mosquitoes. PMID- 26802492 TI - Biokinetic studies of non-complexed siRNA versus nano-sized PEI F25-LMW/siRNA polyplexes following intratracheal instillation into mice. AB - Successful gene therapy requires stability and sufficient bioavailability of the applied drug at the site of action. In the case of RNA interference (RNAi), non viral vectors play a promising role for delivering intact siRNA molecules. We selected a low molecular weight polyethyleneimine (PEI F25-LMW) and investigated the biokinetics of PEI F25-LMW/siRNA polyplexes in comparison to non-complexed siRNA molecules upon intratracheal application into mice. Additionally, a bronchoalveolar lavage was performed to locate the siRNA within the different lung compartments and to analyse possible inflammatory reactions. Liquid scintillation counting of a 32P-label was used to follow the siRNA within the whole body. During the complete observation time more than 75% of the applied dose was found at the target site. The complexation with PEI F25- LMW prevented the siRNA from being degraded and cleared and prolonged its retention time. A low inflammatory reaction was observed on the basis of cell differentiation. Taken together, PEI F25-LMW meets fundamental requirements on non-viral vectors for local pulmonary siRNA delivery. PMID- 26802494 TI - Insulin loaded mucus permeating nanoparticles: Addressing the surface characteristics as feature to improve mucus permeation. AB - AIM: It was the aim of this study to combine two strategies - namely the virus mimicking strategy and the surface PEGylation strategy - in order to generate highly mucus permeating nanocarriers for oral insulin delivery. METHODS: Chondroitin sulphate was covalently conjugated with poly(ethylene glycol) 5 kDa at different degree of modification and with the functionalized polymers NPs were formulated via complexation with chitosan. NPs were characterized by particle size, zeta potential, surface hydrophilicity and permeation ability in porcine mucus and on excised mucosa. RESULTS: The NPs presented a size between 510 and 670 nm and a zeta potential between -1 and -5 mV when dispersed in simulated intestinal fluid. The mucus permeation test revealed a correlation between the NPs hydrophilicity and their ability to move through mucus. A 5-fold higher amount of NPs with the higher degree of PEGylation could permeate through fresh mucus compared to non-PEGylated NPs. Moreover, highly PEGylated NPs showed a 3.7 fold greater ability to be retained in intestinal mucosa against buffer flow compared to unmodified NPs. Finally, insulin was incorporated with a payload of 2.18% and the release profile showed a 65% release within 4h. CONCLUSIONS: Results of this study provide strong evidence for the potential of combining different surface modification strategies in order to improve the mucus permeating properties of NPs for oral peptide delivery. PMID- 26802493 TI - Functional physico-chemical, ex vivo permeation and cell viability characterization of omeprazole loaded buccal films for paediatric drug delivery. AB - Buccal films were prepared from aqueous and ethanolic Metolose gels using the solvent casting approach (40 degrees C). The hydration (PBS and simulated saliva), mucoadhesion, physical stability (20 degrees C, 40 degrees C), in vitro drug (omeprazole) dissolution (PBS and simulated saliva), ex vivo permeation (pig buccal mucosa) in the presence of simulated saliva, ex vivo bioadhesion and cell viability using MTT of films were investigated. Hydration and mucoadhesion results showed that swelling capacity and adhesion was higher in the presence of PBS than simulated saliva (SS) due to differences in ionic strength. Omeprazole was more stable at 20 degrees C than 40 degrees C whilst omeprazole release reached a plateau within 1h and faster in PBS than in SS. Fitting release data to kinetic models showed that Korsmeyer-Peppas equation best fit the dissolution data. Drug release in PBS was best described by zero order via non-Fickian diffusion but followed super case II transport in SS attributed to drug diffusion and polymer erosion. The amount of omeprazole permeating over 2h was 275 ug/cm(2) whilst the formulations and starting materials showed cell viability values greater than 95%, confirming their safety for potential use in paediatric buccal delivery. PMID- 26802495 TI - Characterisation and in vitro stability of low-dose, lidocaine-loaded poly(vinyl alcohol)-tetrahydroxyborate hydrogels. AB - Poly(vinyl alcohol) hydrogels cross-linked with the tetrahydroxyborate anion possess textural and rheological properties that can be used as novel drug-loaded vehicles for application to traumatic wounds. However, addition of soluble drug substances causes concentration-dependent phase separation and rheological changes. The aim of this work was to investigate the effect of adding a local anaesthetic, but keeping the concentration low in an attempt to prevent these changes. Cross-linked hydrogels prepared from three grades of poly(vinyl alcohol) were characterised rheologically. Temperature sweep studies showed an elevated complex viscosity upon moving from 25 degrees C to 80 degrees C, which remained high for 48 h following completion of the cycle. Adhesion to model dermal surfaces achieved a maximum of 2.62 N cm(-2) and were greater than that observed to epidermal substrates, with a strong dependence on the rate of detachment used during testing. An optimised formulation (6% w/w PVA (31-50; 99) and 2% w/w THB) containing lidocaine hydrochloride loaded to an upper maximum concentration of 1.5% w/w was assessed for phase separation and drug crystallisation. After six months, crystallisation was present in formulations containing 0.7% and 1.5% lidocaine HCl. Changes in pH in response to increases in lidocaine loading were low. Drug release was shown to operate via a non-Fickian process for all three concentrations, with 60% occurring after approximately 24h. It can be concluded that using a low concentration of lidocaine hydrochloride in hydrogels based on poly(vinyl alcohol) will result in crystallisation. Furthermore, these hydrogels are unlikely to induce rapid anaesthesia due to the low loading and slow release kinetics. PMID- 26802496 TI - Folate receptor-targeted multimodal polymersomes for delivery of quantum dots and doxorubicin to breast adenocarcinoma: In vitro and in vivo evaluation. AB - In this study, we report the design and delivery of tumor-targeted, quantum dot (QD) and doxorubicin (DOX)-encapsulated PEG-PLGA nanopolymersomes (NPs) for the imaging and chemotherapy of breast cancer. To achieve active cancer targeting, QD and DOX-encapsulated NPs were conjugated with folate for folate-binding protein receptor-guided delivery, which overexpressed in many cancer cells. Hydrophobic DOX and hydrophilic MSA-capped QD were encapsulated in the bilayer and core of the PEG-PLGA nanopolymersomes, respectively. The data show that the formulated NPs sustained DOX release for a period of 12 days. Fluorescence microscopy and MTT assay demonstrated that the developed folate-targeted DOX-QD NPs had higher cytotoxicity than non-targeted NPs and the free form of the drug; moreover, they preferentially accumulated in 4T1 and MCF-7 cells in vitro. In vivo experiments including whole organ tissue-homogenate analysis and organ fluorescence microscopy imaging of BALB/c mice bearing 4T1 breast adenocarcinoma showed that the folate receptor-targeted QD encapsulated NPs accumulate at tumor sites 6h following intravenous injection. Acute toxicity studies of the prepared targeted QD-loaded NPs showed no evidence of long-term harmful histopathological and physiological effects on the treated animals. The in vivo tumor inhibitory effect of folic acid (FA)-QD-DOX NPs demonstrated an augmented therapeutic efficacy of targeted formulation over the non-targeted and free drug. The data obtained illustrate a high potential of the prepared targeted theranostic nanoplatform in the treatment and imaging of breast cancer. This study may open new directions for preparation of QD-based theranostic polymersomes for clinical application. PMID- 26802497 TI - Development of TMTP-1 targeted designer biopolymers for gene delivery to prostate cancer. AB - Designer biopolymers (DBPs) represent state of the art genetically engineered biomacromolecules designed to condense plasmid DNA, and overcome intra- and extra cellular barriers to gene delivery. Three DBPs were synthesized, each with the tumor molecular targeting peptide-1 (TMTP-1) motif to specifically target metastases. Each DBP was complexed with a pEGFP-N1 reporter plasmid to permit physiochemical and biological assay analysis. Results indicated that two of the biopolymers (RMHT and RM3GT) effectively condensed pEGFP-N1 into cationic nanoparticles <100 nm and were capable of transfecting PC-3 metastatic prostate cancer cells. Conversely the anionic RMGT DBP nanoparticles could not transfect PC-3 cells. RMHT and RM3GT nanoparticles were stable in the presence of serum and protected the cargo from degradation. Additionally it was concluded that cell viability could recover post-transfection with these DBPs, which were less toxic than the commercially available transfection reagent Lipofectamine((r)) 2000. With both DBPs, a higher transfection efficacy was observed in PC-3 cells than in the moderately metastatic, DU145, and normal, PNT2-C2, cell lines. Blocking of the TMTP-1 receptors inhibited gene transfer indicating internalization via this receptor. In conclusion RMHT and RM3GT are fully functional DBPs that address major obstacles to gene delivery and target metastatic cells expressing the TMTP 1 receptor. PMID- 26802498 TI - Humidity-corrected Arrhenius equation: The reference condition approach. AB - Accelerated and stress stability data is often used to predict shelf life of pharmaceuticals. Temperature, combined with humidity accelerates chemical decomposition and the Arrhenius equation is used to extrapolate accelerated stability results to long-term stability. Statistical estimation of the humidity corrected Arrhenius equation is not straightforward due to its non-linearity. A two stage nonlinear fitting approach is used in practice, followed by a prediction stage. We developed a single-stage statistical procedure, called the reference condition approach, which has better statistical properties (less collinearity, direct estimation of uncertainty, narrower prediction interval) and is significantly easier to use, compared to the existing approaches. Our statistical model was populated with data from a 35-day stress stability study on a laboratory batch of vitamin tablets and required mere 30 laboratory assay determinations. The stability prediction agreed well with the actual 24-month long term stability of the product. The approach has high potential to assist product formulation, specification setting and stability statements. PMID- 26802499 TI - Alcohol and drinking cultures in Vietnam: A review. AB - BACKGROUND: Epidemiological data suggest that national levels of alcohol consumption have increased rapidly in contemporary Vietnam; concomitantly, social and public health harms associated with alcohol use are on the rise. METHODS: Over the last decade, a research literature on alcohol use in Vietnam has begun to develop. RESULTS: A consideration of this literature indicates lines of analysis to be extended and gaps to be filled. CONCLUSION: This synopsis provides an overview of the major trends that studies have addressed, evaluates the state of research to date, and suggests avenues for further research on alcohol use in this newly middle-income nation. PMID- 26802500 TI - Use of a rat ex-vivo testis culture method to assess toxicity of select known male reproductive toxicants. AB - Due to the complex physiology of the testes, in vitro models have been largely unsuccessful at modeling testicular toxicity in vivo. We conducted a pilot study to evaluate the utility of the Durand ex vivo rat seminiferous tubule culture model [1-3] that supports spermatogenesis through meiosis II, including the formation of round spermatids. We used this system to evaluate the toxicity of four known testicular toxicants: 1,3-dinitrobenzene (DNB), 2-methoxyacetic acid (MAA), bisphenol A (BPA), and lindane over 21 days of culture. This organotypic culture system demonstrated the ability to successfully model in vivo testicular toxicity (Sertoli cell toxicity and disruption of meiosis) for all four compounds. These findings support the application of this system to study molecules and evaluate mechanisms of testicular toxicity. PMID- 26802501 TI - Interpreting the National Hospital Ambulatory Medical Care Survey: United States Emergency Department Opioid Prescribing, 2006-2010. AB - OBJECTIVES: Prescription opioid overdoses are a leading cause of death in the United States. Emergency departments (EDs) are potentially high-risk environments for doctor shopping and diversion. The hypothesis was that opioid prescribing rates from the ED have increased over time. METHODS: The authors analyzed data on ED discharges from the 2006 through 2010 NHAMCS, a probability sample of all U.S. EDs. The outcome was documentation of an opioid prescription on discharge. The primary independent predictor was time. Covariates included severity of pain, a pain-related discharge diagnosis, age, sex, race, payer, hospital ownership, and geographic location of hospital. Up to three discharge diagnoses were available in NHAMCS to identify "pain-related" (e.g., back pain, fracture, dental/jaw pain, nephrolithiasis) ED visits. Multivariate logistic regression was performed to assess the independent associations between opioid prescribing and predictors. All analyses incorporated NHAMCS survey weights, and all results are presented as national estimates. RESULTS: Opioids were prescribed for 18.7% (95% confidence interval = 17.7% to 19.7%) of all ED discharges, representing 18.8 million prescriptions per year. There were no significant temporal trends in opioid prescribing overall (adjusted p = 0.93). Pain-related discharge diagnoses that received the top three highest proportion of opioids prescriptions included nephrolithiasis (62.1%), neck pain (51.6%), and dental/jaw pain (49.7%). A pain related discharge diagnosis, non-Hispanic white race, older age, male sex, uninsured status, and Western region were positively associated with opioid prescribing (p < 0.05). CONCLUSIONS: No temporal trend toward increased prescribing from 2006 to 2012 was found. These results suggest that problems with opioid overprescribing are multifactorial and not solely rooted in the ED. PMID- 26802503 TI - Hippocampal subfield analysis in medication-naive female patients with major depressive disorder. AB - BACKGROUND: Hippocampal volume loss is known as the best-replicated finding of structural brain imaging studies on major depressive disorder (MDD). Several evidences suggest localized mechanisms of hippocampal neuroplasticity lead the brain imaging studies on the hippocampus and MDD to perform analyses in the subfield level. The aim of this study was to investigate the differences in total and subfield hippocampal volumes, between medication-naive female MDD patients and healthy controls, through automated segmentation and volumetric methods. METHODS: Twenty medication-naive female patients diagnosed with MDD and 21 age matched healthy controls, underwent T1-weighted structural magnetic resonance scanning. Total volumes of both hippocampi and subfield regions were calculated by the automated procedure for volumetric measures implemented in FreeSurfer and automated segmentation method by Van Leemput et al. RESULTS: We observed patients to have significantly smaller volumes of the left hippocampus, subiculum, cornu ammonis 2-3, cornu ammonis 4-dentate gyrus, and right subiculum compared to healthy controls. There were no significant predictors for these subfield region volumes among the illness burden-related parameters including duration of illness, number of depressive episodes, severity of depressive symptoms and memory performances. LIMITATIONS: Our findings relied on the data of only female participants. CONCLUSIONS: We found significant volume reductions in several hippocampal subfield regions in medication-naive female MDD patients. Our results are consistent with neurobiological evidences on hippocampal neuroplasticity in MDD, and replicate previous findings that suggest morphologic changes of hippocampal subfields in MDD patients. PMID- 26802502 TI - Age-period-cohort analysis of the suicide rate in Korea. AB - BACKGROUND: The suicide rate has been increasing in Korea, and the country now has the highest rank in the world. This study aimed to present the long-term trends in Korea's suicide rate using Joinpoint analysis and age-period-cohort (APC) modeling. METHODS: The population and the number of suicides for each five year age group were obtained from the National Statistical Office for the period 1984-2013 for Koreans aged 10 years and older. We determined the changes in the trends in age-standardized mortality rates using Joinpoint. APC modeling was performed to describe the trends in the suicide rate using the intrinsic estimator method. RESULTS: The age-standardized suicide rate in men rapidly increased from 1989 to 2004, and slightly increased thereafter, whereas the suicide rate in women increased from 1989 to 2009 and then decreased thereafter. Within the same period, the suicide rate was higher among the older age groups than in the younger groups. Within the same birth cohort, the suicide rate of the older groups was also higher than that in the younger groups. Within the same age group, the suicide rate of the younger cohorts was higher than it was in the older cohorts. In the APC modeling, old age, recent period, and having been born before 1924 were associated with higher suicide rates. LIMITATIONS: The accuracy and completeness of the suicide rate data may lead to bias. CONCLUSIONS: This study showed an increasing trend in the suicide rates for men and women after 1989. These trends may be mainly attributed to cohort effects. PMID- 26802504 TI - Resting vagal tone is negatively associated with suicide ideation. AB - BACKGROUND: The present study aimed at investigating whether resting vagally mediated heart rate variability (HRV) as a trait-like biomarker of cognitive inhibitory control capacity is related to suicide ideation in a sample without suicide attempt history. METHODS: Thirty-seven healthy students participated voluntarily (18 to 34 years, M=24.5, SD=4.1; 73.0% female). Time and frequency measures of HRV were derived from an electrocardiogram that was recorded using Einthoven's Triangle lead II. Participants filled in the Rasch-based Depression Screening and four questions concerning lifetime suicide ideation (SI). Bivariate Pearson's and partial (controlling for depression severity) correlation coefficients were calculated between SI and measures of vagally mediated HRV. RESULTS: A significant correlation between the ln10-transformed high-frequency band of resting vagally mediated HRV and SI was found (r=-.33, p<.05). Correlations did not change substantially when controlling for depression. Mean heart rate as a time domain measure also significantly correlated with SI while controlling for depression (r=.36, p<.05). A trend correlation between SI and Root Mean Square of Successive Differences between interbeat intervals emerged. LIMITATIONS: SI was assessed with a composite score of four items measuring SI. Future studies should consider using more comprehensive assessment instruments. CONCLUSIONS: The relation between resting vagally mediated HRV and suicide ideation may be interpreted as indicating that reduced inhibitory cognitive control capacity may be a risk factor for suicidality. It may act already early in the suicidal process, before suicidal behavior develops and should be further investigated as potentially clinically important physiological predictor of suicidality. PMID- 26802505 TI - Deep brain stimulation of the posterior gyrus rectus region for treatment resistant depression. AB - BACKGROUND: Deep brain stimulation (DBS) represents an alternative symptomatic treatment for major depressive disorder in case of failure of pharmacotherapy. The sub-genual cingulate-Brodmann area 25 (CG-25), is one of the most widely used targets for electrode implantation. Given the diverging clinical outcome after DBS, there is a pressing need for in-depth study of brain anatomy and function allowing accurate and reliable prognosis before surgery. METHODS: We studied five treatment-resistant major depressive disorder patients planned to undergo DBS targeting the CG-25. Before surgery, we acquired high-resolution magnetic resonance (MR) diffusion-weighted images for each patient followed by post surgery MRI for electrode localization. To estimate individual anatomical connectivity pattern of the active contact location we performed probabilistic diffusion tractography intra-individually. We then correlated connectivity patterns with outcome assessed with standardized clinical tests. Connectivity results were compared between DBS responders and non-responders. RESULTS: We observed in one patient an excellent clinical response after DBS of the bilateral posterior gyrus rectus rather than the initially targeted CG-25. The remaining four patients with DBS of the CG-25 were considered as non-responders. In the case patient, we demonstrate a strong connectivity of the stimulated regions to the medial prefrontal cortex (mPFC), which contrasted to the lower mPFC connectivity in non-responders. LIMITATIONS: Confirmation in larger cohorts is needed. CONCLUSIONS: We propose the posterior gyrus rectus as viable alternative new target for DBS in major depressive disorder. High connectivity between target and mPFC supports the pivotal role of this region in brain networks involved in mood processing. PMID- 26802506 TI - Is there cardiac risk in panic disorder? An updated systematic review. AB - BACKGROUND: The recognized relationship between panic disorder (PD) and cardiac disorders (CDs) is not unequivocal. We reviewed the association between PD and coronary artery disease (CAD), arrhythmias, cardiomyopathies, and sudden cardiac death. METHODS: We undertook an updated systematic review, according to PRISMA guidelines. Relevant studies dating from January 1, 2000, to December 31, 2014, were identified using the PubMed database and a review of bibliographies. The psychiatric and cardiac diagnostic methodology used in each study was then to very selective inclusion criteria. RESULTS: Of 3044 studies, 14 on CAD, 2 on cardiomyopathies, and 1 on arrhythmias were included. Overall, the studies supported a panic-CAD association. Furthermore, in some of the studies finding no association between current full-blown PD and CAD, a broader susceptibility to panic, manifesting as past PD, current agoraphobia, or subthreshold panic symptoms, appeared to be relevant to the development of CAD. Preliminary data indicated associations between panic, arrhythmias, and cardiomyopathies. LIMITATIONS: The studies were largely cross-sectional and conducted in cardiological settings. Only a few included blind settings. The clinical conditions of patients with CDs and the qualifications of raters of psychiatric diagnoses were highly heterogeneous. CDs other than CAD had been insufficiently investigated. CONCLUSIONS: Our review supported a relationship between PD and CDs. Given the available findings and the involvement of the cardiorespiratory system in the pathophysiology of PD, an in-depth investigation into the panic-CDs association is highly recommended. This should contribute to improved treatment and prevention of cardiac events and/or mortality, linked to PD. PMID- 26802507 TI - Pre-attentive dysfunction of musical processing in major depressive disorder: A mismatch negativity study. AB - BACKGROUND: Deficits of pre-attentive information processing have been frequently found in patients with major depressive disorder, nevertheless the results are quite inconsistent due to clinical heterogeneity and methodological difference. Cognitive processing of music is a useful tool for investigating human cognition and its underlying brain mechanisms. Although general auditory processing and perception of musical sound are hampered in patients with MDD, whether the deficits in musical processing begin from pre-attentive stage is not well investigated yet. The present study aimed to investigate the MMN of musical sound in patients with MDD. METHOD: MMN responses to different musical features were compared in 20 patients with MDD and 20 age-matched healthy controls. The multi feature paradigm was used to examine automatic change detection of six different musical sound features (pitch, timbre, location, intensity, slide, rhythm) in a complex musical context. Severity of depression and co-morbid anxiety were evaluated using the Hamilton Rating Scale of Depression (HRSD-17) and the Hamilton Anxiety Rating Scale (HAMA). RESULTS: MMNs were obtained with all deviants. The timbre-MMN was significantly larger in MDD patients than in healthy controls, while the other deviants (pitch, location, intensity, slide and rhythm) elicited similar MMN across groups. For MDD patients, the amplitudes and latencies of MMNs did not correlate with severity of depression or co-morbid anxiety. LIMITATIONS: The sample size in this study is relatively small. CONCLUSION: Patients with MDD do not perform at the same level as controls in automatic change detection of timbre. This dysfunction is considered to be a trait-dependent feature of MDD. PMID- 26802508 TI - A failure of suppression within the default mode network in depressed adolescents with compulsive internet game play. AB - BACKGROUND: Individuals who are chronic, compulsive video game players experience an elevated incidence of major depression. Excessive or problematic game play can interact with depression clinically, and may magnify impulsive behavior associated with video gaming. METHODS: Functional brain imaging was performed during a Wisconsin Card Sorting Test (WCST) task in 42 healthy control and 95 volunteers seeking treatment for compulsive video game playing, including 60 participants without major depression (pure internet gaming disorder, pure IGD) and 35 participants comorbid with major depression (IGD+MDD). RESULTS: In response to the WCST in contrast to fixation, activation was observed in canonical brain attentional networks including bilateral intraparietal sulcus, frontal eye fields, and middle temporal cortical regions as well as dorsolateral prefrontal, inferior parietal and anterior insula, anterior cingulate cortex in all participants. For WCST>Fixation contrasts, the IGD+MDD group exhibited greater relative activation within the left hippocampus, compared to healthy control participants. For WCST>Fixation contrasts, the IGD+MDD group exhibited greater relative activation within the left hippocampus and the right parahippocampal gyrus immediately posterior to the hippocampus, compared to the pure IGD group. CONCLUSIONS: In cohorts of individuals with a history of compulsive internet game play, individuals with depression showed failure to suppress default mode network activity during an attentionally demanding task, compared to individuals without depression, including comparison groups with and without a history of compulsive video gaming. This reduced suppression of the brain regions within the default mode network may be a consequence of depressive neurophysiology or represent a predisposition for depression within compulsive game players. PMID- 26802509 TI - Activation of migration of endogenous stem cells by erythropoietin as potential rescue for neurodegenerative diseases. AB - Neurodegenerative disorders such as Alzheimer's disease (AD) are characterized by progressive cognitive dysfunction and memory loss. There is deposition of amyloid plaques in the brain and subsequent neuronal loss. Neuroinflammation plays a key role in the pathogenesis of AD. There is still no effective curative therapy for these patients. One promising strategy involves the stimulation of endogenous stem cells. This study investigated the therapeutic effect of erythropoietin (EPO) in neurogenesis, and proved its manipulation of the endogenous mesenchymal stem cells in model of lipopolysaccharide (LPS)-induced neuroinflammation. METHODS: Forty five adult male mice were divided equally into 3 groups: Group I (control), group II (LPS untreated group): mice were injected with single dose of lipopolysaccharide (LPS) 0.8 mg/kg intraperitoneally (ip) to induce neuroinflammation, group III (EPO treated group): in addition to (LPS) mice were further injected with EPO in dose of 40 MUg/kg of body weight three times weekly for 5 consecutive weeks. Groups were tested for their locomotor activity and memory using open field test and Y-maze. Cerebral specimens were subjected to histological and morphometric studies. Glial fibrillary acidic protein (GFAP) and mesenchymal stem cell marker CD44 were assessed using immunostaining. Gene expression of brain derived neurotrophic factor (BDNF) was examined in brain tissue. RESULTS: LPS decreased locomotor activity and percentage of correct choices in Y-maze test. Cerebral sections of LPS treated mice showed increased percentage area of dark nuclei and amyloid plaques. Multiple GFAP positive astrocytes were detected in affected cerebral sections. In addition, decrease BDNF gene expression was noted. On the other hand, EPO treated group, showed improvement in locomotor and cognitive function. Examination of the cerebral sections showed multiple neurons exhibiting less dark nuclei and less amyloid plaques in comparison to the untreated group. GFAP positive astrocytes were also reduced. Cerebral sections of the EPO treated group showed multiple branched and spindle CD44 positive cells inside and around blood vessels more than in LPS group. This immunostaining was negative in the control group. EPO administration increased BDNF gene expression. CONCLUSION: This study proved that EPO provides excellent neuroprotective and neurotrophic effects in vivo model of LPS induced neuroinflammation. It enhances brain tissue regeneration via stimulation of endogenous mesenchymal stem cells proliferation and their migration to the site of inflammation. EPO also up regulates cerebral BDNF expression and production, which might contributes to EPO mediated neurogenesis. It also attenuates reactive gliosis thus reduces neuroinflammation. These encouraging results obtained with the use of EPO proved that it may be a promising candidate for future clinical application and treatment of neurodegenerative diseases. PMID- 26802510 TI - Neuroprotective effects of penehyclidine hydrochloride against cerebral ischemia/reperfusion injury in mice. AB - Various reports have suggested that penehyclidine hydrochloride (PHC), a new cholinergic antagonist, exhibits a variety of biological actions such as anti tumor and cardioprotective effects. This study aimed to investigate the effects of PHC on cerebral ischemia/reperfusion (I/R) injury and evaluate whether the c Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (p38MAPK) pathway is involved in the protective effects of PHC. Male C57BL/6 mice were randomly assigned to Sham group, ischemia/reperfusion (I/R) group, I/R+PHC (0.1mg/kg) group, and I/R+PHC (1mg/kg) group. Mice were subjected to 2h of transient middle cerebral artery occlusion, followed by 24h of reperfusion except the mice in the sham group. Neurological deficits, infarct volume, brain water content, blood-brain barrier (BBB) integrity, and neuronal apoptosis were evaluated. The levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), superoxide production, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were measured. The expressions of the key proteins in the JNK/p38MAPK pathway were detected using the Western blot. The results suggested that compared to the I/R group, the PHC treated group showed improved neurological deficits and BBB integrity, and reduced infarction volume, brain water content, and apoptosis. In addition, PHC significantly suppressed the levels of TNF-alpha, IL-1beta, superoxide production, and MDA, and increased the levels of SOD and GSH-Px. Finally, PHC significantly downregulated the phosphorylation of JNK, p38MAPK, and c-Jun, indicating PHC protects against cerebral I/R injury by downregulating the JNK/p38MAPK signaling pathway. PMID- 26802511 TI - Music exposure improves spatial cognition by enhancing the BDNF level of dorsal hippocampal subregions in the developing rats. AB - Previous research has shown that dorsal hippocampus plays an important role in spatial memory process. Music exposure can enhance brain-derived neurotrophic factor (BDNF) expression level in dorsal hippocampus (DH) and thus enhance spatial cognition ability. But whether music experience may affect different subregions of DH in the same degree remains unclear. Here, we studied the effects of exposure to Mozart K.448 on learning behavior in developing rats using the classical Morris water maze task. The results showed that early music exposure could enhance significantly learning performance of the rats in the water maze test. Meanwhile, the BDNF/TrkB level of dorsal hippocampus CA3 (dCA3) and dentate gyrus (dDG) was significantly enhanced in rats exposed to Mozart music as compared to those without music exposure. In contrast, the BDNF/TrkB level of dorsal hippocampus CA1 (dCA1) was not affected. The results suggest that the spatial memory improvement by music exposure in rats may be associated with the enhanced BDNF/TrkB level of dCA3 and dDG. PMID- 26802512 TI - Structural covariance networks in the mouse brain. AB - The presence of networks of correlation between regional gray matter volume as measured across subjects in a group of individuals has been consistently described in several human studies, an approach termed structural covariance MRI (scMRI). Complementary to prevalent brain mapping modalities like functional and diffusion-weighted imaging, the approach can provide precious insights into the mutual influence of trophic and plastic processes in health and pathological states. To investigate whether analogous scMRI networks are present in lower mammal species amenable to genetic and experimental manipulation such as the laboratory mouse, we employed high resolution morphoanatomical MRI in a large cohort of genetically-homogeneous wild-type mice (C57Bl6/J) and mapped scMRI networks using a seed-based approach. We show that the mouse brain exhibits robust homotopic scMRI networks in both primary and associative cortices, a finding corroborated by independent component analyses of cortical volumes. Subcortical structures also showed highly symmetric inter-hemispheric correlations, with evidence of distributed antero-posterior networks in diencephalic regions of the thalamus and hypothalamus. Hierarchical cluster analysis revealed six identifiable clusters of cortical and sub-cortical regions corresponding to previously described neuroanatomical systems. Our work documents the presence of homotopic cortical and subcortical scMRI networks in the mouse brain, thus supporting the use of this species to investigate the elusive biological and neuroanatomical underpinnings of scMRI network development and its derangement in neuropathological states. The identification of scMRI networks in genetically homogeneous inbred mice is consistent with the emerging view of a key role of environmental factors in shaping these correlational networks. PMID- 26802513 TI - Sulfentrazone dechlorination by iron-nickel bimetallic nanoparticles. AB - The sulfentrazone dechlorination using bimetallic nanoparticles of Fe/Ni was studied. Different variables that could influence the sulfentrazone conversion were investigated, such as nitrogen atmosphere, pH and dosage of the nanoparticles and initial concentration of sulfentrazone. The best results were obtained using controlled pH (pH 4.0) and 1.0 g L(-1) of nanomaterials, resulting in 100 % conversion in only 30 min. Kinetic studies were also conducted, evaluating the influence of different nanoparticle dosages (1.0 to 4.0 g L(-1)), system temperatures (20 to 35 degrees C) and nickel levels in the composition of the nanomaterials (0.025 to 0.10 gNi/gFe). The mechanism of sulfentrazone conversion has changed due a direct reduction on the catalytic activity sites and indirect reduction by atomic hydrogen. Both mechanisms have followed pseudo-first order models. The conversion rate improved when the dosage of the nanomaterials, system temperature and nickel content in the composition of the nanocomposites were increased. Finally, the conversion products were elucidated by mass spectrometry and toxicity assays were performed using Daphnia Similis. The results showed that the dechlorination product is less toxic than sulfentrazone. PMID- 26802514 TI - Pesticides in the Ebro River basin: Occurrence and risk assessment. AB - In this study, 50 pesticides were analyzed in the Ebro River basin in 2010 and 2011 to assess their impact in water, sediment and biota. A special emphasis was placed on the potential effects of both, individual pesticides and their mixtures, in three trophic levels (algae, daphnia and fish) using Risk Quotients (RQs) and Toxic Units (TUs) for water and sediments. Chlorpyrifos, diazinon and carbendazim were the most frequent in water (95, 95 and 70% of the samples, respectively). Imazalil (409.73 ng/L) and diuron (150 ng/L) were at the highest concentrations. Sediment and biota were less contaminated. Chlorpyrifos, diazinon and diclofenthion were the most frequent in sediments (82, 45 and 21% of the samples, respectively). The only pesticide detected in biota was chlorpyrifos (up to 840.2 ng g(-1)). Ecotoxicological risk assessment through RQs showed that organophosphorus and azol presented high risk for algae; organophosphorus, benzimidazoles, carbamates, juvenile hormone mimic and other pesticides for daphnia, and organophosphorus, azol and juvenile hormone mimics for fish. The sum TUsite for water and sediments showed values < 1 for the three bioassays. In both matrices, daphnia and fish were more sensitive to the mixture of pesticide residues present. PMID- 26802515 TI - Enhanced removal of sulfonamide antibiotics by KOH-activated anthracite coal: Batch and fixed-bed studies. AB - The presence of sulfonamide antibiotics in aquatic environments poses potential risks to human health and ecosystems. In the present study, a highly porous activated carbon was prepared by KOH activation of an anthracite coal (Anth-KOH), and its adsorption properties toward two sulfonamides (sulfamethoxazole and sulfapyridine) and three smaller-sized monoaromatics (phenol, 4-nitrophenol and 1,3-dinitrobenzene) were examined in both batch and fixed-bed adsorption experiments to probe the interplay between adsorbate molecular size and adsorbent pore structure. A commercial powder microporous activated carbon (PAC) and a commercial mesoporous carbon (CMK-3) possessing distinct pore properties were included as comparative adsorbents. Among the three adsorbents Anth-KOH exhibited the largest adsorption capacities for all test adsorbates (especially the two sulfonamides) in both batch mode and fixed-bed mode. After being normalized by the adsorbent surface area, the batch adsorption isotherms of sulfonamides on PAC and Anth-KOH were displaced upward relative to the isotherms on CMK-3, likely due to the micropore-filling effect facilitated by the microporosity of adsorbents. In the fixed-bed mode, the surface area-normalized adsorption capacities of Anth KOH for sulfonamides were close to that of CMK-3, and higher than that of PAC. The irregular, closed micropores of PAC might impede the diffusion of the relatively large-sized sulfonamide molecules and in turn led to lowered fixed-bed adsorption capacities. The overall superior adsorption of sulfonamides on Anth KOH can be attributed to its large specific surface area (2514 m(2)/g), high pore volume (1.23 cm(3)/g) and large micropore sizes (centered at 2.0 nm). These findings imply that KOH-activated anthracite coal is a promising adsorbent for the removal of sulfonamide antibiotics from aqueous solution. PMID- 26802516 TI - Methods of information theory and algorithmic complexity for network biology. AB - We survey and introduce concepts and tools located at the intersection of information theory and network biology. We show that Shannon's information entropy, compressibility and algorithmic complexity quantify different local and global aspects of synthetic and biological data. We show examples such as the emergence of giant components in Erdos-Renyi random graphs, and the recovery of topological properties from numerical kinetic properties simulating gene expression data. We provide exact theoretical calculations, numerical approximations and error estimations of entropy, algorithmic probability and Kolmogorov complexity for different types of graphs, characterizing their variant and invariant properties. We introduce formal definitions of complexity for both labeled and unlabeled graphs and prove that the Kolmogorov complexity of a labeled graph is a good approximation of its unlabeled Kolmogorov complexity and thus a robust definition of graph complexity. PMID- 26802517 TI - Regulation of midbody formation and function by mitotic kinases. AB - Cytokinesis is the final phase of cell division and safeguards the correct distribution of genomic and cytoplasmic materials between the two nascent daughter cells. The final separation, or abscission, of the daughter cells depends on the proper assembly of an organelle at the intercellular bridge, the midbody, which acts as a platform for the recruitment and organisation of various proteins involved in both the control and execution of the abscission process. Recent studies have led to the identification of the mechanisms, signalling pathways and molecules that control the two tightly linked processes of midbody formation and abscission. Here we review our current knowledge of the role that mitotic kinases play in these processes and offer our perspectives on the potential future challenges that await researchers in the field. PMID- 26802518 TI - Retrieving autobiographical memories: How different retrieval strategies associated with different cues explain reaction time differences. AB - Previous research has shown that memories cued by concrete concepts, such as objects, are retrieved faster than those cued by more abstract concepts, such as emotions. This effect has been explained by the fact that more memories are directly retrieved from object versus emotion cues. In the present study, we tested whether RT differences between memories cued by emotion versus object terms occur not only because object cues elicit direct retrieval of more memories (Uzer, Lee, & Brown, 2012), but also because of differences in memory generation in response to emotions versus objects. One hundred university students retrieved memories in response to basic-level (e.g. orange), superordinate-level (e.g. plant), and emotion (e.g. surprised) cues. Retrieval speed was measured and participants reported whether memories were directly retrieved or generated on each trial. Results showed that memories were retrieved faster in response to basic-level versus superordinate-level and emotion cues because a) basic-level cues elicited more directly retrieved memories, and b) generating memories was more difficult when cues were abstract versus concrete. These results suggest that generative retrieval is a cue generation process in which additional cues that provide contextual information including the target event are produced. Memories are retrieved more slowly in response to emotion cues in part because emotion labels are less effective cues of appropriate contextual information. This particular finding is inconsistent with the idea that emotion is a primary organizational unit for autobiographical memories. In contrast, the difficulty of emotional memory generation implies that emotions represent low-level event information in the organization of autobiographical memory. PMID- 26802519 TI - Biocompatibility and antibacterial activity of the Adathoda vasica Linn extract mediated silver nanoparticles. AB - The aim of this study is to investigate the biocompatibility and anti-Vibrio efficacy of green synthesized silver nanoparticles (AgNPs) using an aqueous leaf extract of Adathoda vasica (A. vasica). The green synthesized silver nanoparticles were characterized by UV-vis, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX). A. vasica AgNPs showed significant antibacterial activity against Vibrio parahaemolyticus in agar bioassay and well diffusion method. Further, nanoparticles interactions with bacteria and its antibacterial activity were confirmed by CLSM analysis. In vivo evaluation results confirmed that synthesized A. vasica AgNPs had good antibacterial efficacy and also nontoxic to the Artemia nauplii. PMID- 26802520 TI - Biosynthesis of silver nanoparticles using a probiotic Bacillus licheniformis Dahb1 and their antibiofilm activity and toxicity effects in Ceriodaphnia cornuta. AB - In the present study, we synthesized and characterized a probiotic Bacillus licheniformis cell free extract (BLCFE) coated silver nanoparticles (BLCFE AgNPs). These BLCFE-AgNPs were characterized by UV-visible spectrophotometer, XRD, EDX, FTIR, TEM and AFM. A strong surface plasmon resonance centered at 422 nm in UV-visible spectrum indicates the formation of AgNPs. The XRD spectrum of silver nanoparticles exhibited 2theta values corresponding to the silver nanocrystal. TEM and AFM showed the AgNPs were spherical in shape within the range of 18.69-63.42 nm and the presence of silver was confirmed by EDX analysis. Light and Confocal Laser Scanning Microscope (CLSM) images showed a weak adherence and disintegrated biofilm formation of Vibrio parahaemolyticus Dav1 treated with BLCFE-AgNPs compared to control. This result suggests that BLCFE AgNps may be used for the control of biofilm forming bacterial populations in the biomedical field. In addition, acute toxicity results concluded that BLCFE-AgNPs were less toxic to the fresh water crustacean Ceriodaphnia cornuta (50 MUg/ml) when compared to AgNO3 (22 MUg/ml). This study also reports a short term analysis (24 h) of uptake and depuration of BLCFE-AgNPs in C. cornuta. PMID- 26802521 TI - First record of protozoan parasites in cyprinid fish, Schizothorax niger Heckel, 1838 from Dal lake in Kashmir Himalayas with study on their pathogenesis. AB - Trichodina heterodentata Duncan, 1977 and Ichthyophthirius multifiliis Fouquet, 1876 obtained from gills during a parasitological survey conducted for the protozoan parasitic fauna of Schizothorax niger a snow trout in Dal Lake, Kashmir, India during the period October 2013 and March 2015. Thirty out of 180 fish were found infected with protozoan parasites. During the study of their pathogenecity the most common deteriorating signs observed in gill tissue were necrosis, hypertrophy, hyperplasia and fusion of secondary lamellae. Prevalence of infection was found to be 16.66%. This is the first record of the protozoan fauna of the schizothoracines from Kashmir valley, India. PMID- 26802522 TI - Antibiofilm formation and anti-adhesive property of three mediterranean essential oils against a foodborne pathogen Salmonella strain. AB - Plant extracts, and their essential oils (EOs) are rich in a wide variety of secondary metabolites with antimicrobial properties. Our aim was to determine the bioactive compound in three mediterranean essential oils belonging to Lamiaceae family, Satureja montana L., Thymus vulgaris L. and Rosmarinus officinalis L., and to assess their antimicrobial, antibiofilm and anti-adhesive potentials against a foodborne pathogen Salmonella strain. The antibacterial activity of EOs and its biofilm inhibition potencies were investigated on 2 reference strains Salmonella typhimurium and 12 Salmonella spp. isolated from food. Biofilm inhibition were assessed using the 2, 3-bis [2-methyloxy-4-nitro-5-sulfophenyl] 2H-tetrazolium-5-carboxanilide (XTT) reduction assay. The analytical data indicated that various monoterpene hydrocarbons and phenolic monoterpenes constitute the major components of the oils, but their concentrations varied greatly among the oils examined. Our results showed that S. montana L. and T. vulgaris L. essential oils possess remarkable anti biofilm, anti-adhesive and bactericidal properties, compared to R. officinalis EO. There is an indication that Rosmary EO might inhibit biofilm formation at higher concentrations. Therefore, the witer savory and thyme EOs represent a source of natural compounds that exhibit potentials for use in food systems to prevent the growth of foodborne bacteria and extend the shelf life of the processed food. PMID- 26802523 TI - Complete genome sequence and comparative genome analysis of the Paenibacillus mucilaginosus K02. AB - AIM: Paenibacillus mucilaginosus (P. mucilaginosus) K02 is implicated in mineral weathering. However, relevant molecular mechanisms remain obscure. The study aims to uncover the bacterium's physiological processes using genomic approaches. METHODS AND RESULTS: Genomic DNA from P. mucilaginosus K02 was sequenced using high-throughput Solexa sequencing technology and then conducted for Clusters of Orthologous Group (COG) annotation. Thereafter, genome sequences of K02 were compared with two strains, 3016 and KNP414. Mummer was applied for collinearity analysis of three P. mucilaginosus genomes. BLAST was used to identify pan and core genes in these strains. Finally, a phylogenetic tree was constructed using the maximum likelihood method by TreeBeST. Complete genome sequence of P. mucilaginosus K02 indicated the strain comprises one circular chromosome with 8,819,200 bases containing 58.3% GC content and 84.75% coding regions. A total of 7299 predicted ORFs were identified in the genome, among them, several genes were related to carbonic anhydrase (CA), and exopolysaccharide biosynthesis and secretion. Moreover, proteins of the predicted genes were annotated in COG categories such as "Carbohydrate transport and metabolism" and "Inorganic ion transport and metabolism." In comparison with KNP414 and 3016, K02 exhibited chromosomal recombination or transposition. A total of 6662 core genes were identified among three P. mucilaginosus strains. The phylogenomic study indicated that P. mucilaginosus K02 was clustered with P. mucilaginosus strains 3016 and KNP414. CONCLUSIONS: In P. mucilaginosus K02, genes related to CA and exopolysaccharide biosynthesis and secretion, and that involved in metabolism related processes might play significant roles in mineral weathering. PMID- 26802524 TI - Synergistic approach for treatment of chicken coccidiosis using berberine--A plant natural product. AB - Despite the advent of anticoccidial drugs and vaccines, coccidiosis continues to result in substantial economic losses to the poultry industry. Berberine, a natural alkaloid is well known in studies involving synergistic approaches, thereby reducing the dosage of principal drugs. Therefore, a study was designed to see whether a synergistic anticoccidial effect could be obtained between amprolium and berberine, in vivo using broiler chicken. Anticoccidial activity was measured in comparison to the reference drug amprolium on the basis of oocyst output reduction, mean weight gain and feed conversion ratio. Oocyst output was measured using Mc-Masters counting technique. Different combinations of berberine and amprolium were tested and out of which 1:1 ratio was the most effective for controlling these parasites. Oral gavaging of 100(50 + 50) mg/kg body weight of 1:1 ratio of amprolium and berberine caused the equivalent reduction in number of oocysts (38.85 +/- 9.61) one day prior to that of standard drug amprolium (49.95 +/- 16.65) as well as pure berberine (44.4 +/- 9.61) used in the study. Weight gain of birds was also highest in the synergistic group (1547.43 +/- 12.86) among all the infected groups. Besides feed conversion ratio in the synergistic group was also better (1.387 +/- 0.026). The results of this study proved the effectiveness of both amprolium and berberine and revealed synergism between amprolium and berberine against coccidian oocysts, confirmed by significant reduction in the number of coccidian oocysts shed in the feces, leading to better weight gain and improved feed conversion ratio. The study deep-rooted the synergistic potential of berberine, a natural bioactive compound for controlling a protozoan parasite and the results of this study corroborate with its use for treatment of severe diarrhoea, amoebiasis and intestinal infections. PMID- 26802525 TI - PBPK modeling of the cis- and trans-permethrin isomers and their major urinary metabolites in rats. AB - Permethrin, a pyrethroid insecticide, is suspected to induce neuronal and hormonal disturbances in humans. The widespread exposure of the populations has been confirmed by the detection of the urinary metabolites of permethrin in biomonitoring studies. Permethrin is a chiral molecule presenting two forms, the cis and the trans isomers. Because in vitro studies indicated a metabolic interaction between the trans and cis isomers of permethrin, we adapted and calibrated a PBPK model for trans- and cis-permethrin separately in rats. The model also describes the toxicokinetics of three urinary metabolites, cis- and trans-3-(2,2 dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (cis- and trans-DCCA), 3-phenoxybenzoic acid (3-PBA) and 4'OH-phenoxybenzoic acid (4' OH-PBA). In vivo experiments performed in Sprague-Dawley rats were used to calibrate the PBPK model in a Bayesian framework. The model captured well the toxicokinetics of permethrin isomers and their metabolites including the rapid absorption, the accumulation in fat, the extensive metabolism of the parent compounds, and the rapid elimination of metabolites in urine. Average hepatic clearances in rats were estimated to be 2.4 and 5.7 L/h/kg for cis- and trans permethrin, respectively. High concentrations of the metabolite 4'-OH-PBA were measured in urine compared to cis- and trans-DCCA and 3-PBA. The confidence in the extended PBPK model was then confirmed by good predictions of published experimental data obtained using the isomers mixture. The extended PBPK model could be extrapolated to humans to predict the internal dose of exposure to permethrin from biomonitoring data in urine. PMID- 26802527 TI - In-syringe reversed dispersive liquid-liquid microextraction for the evaluation of three important bioactive compounds of basil, tarragon and fennel in human plasma and urine samples. AB - In the present study, an efficient and environmental friendly method (called in syringe reversed dispersive liquid-liquid microextraction (IS-R-DLLME)) was developed to extract three important components (i.e. para-anisaldehyde, trans anethole and its isomer estragole) simultaneously in different plant extracts (basil, fennel and tarragon), human plasma and urine samples prior their determination using high-performance liquid chromatography. The importance of choosing these plant extracts as samples is emanating from the dual roles of their bioactive compounds (trans-anethole and estragole), which can alter positively or negatively different cellular processes, and necessity to a simple and efficient method for extraction and sensitive determination of these compounds in the mentioned samples. Under the optimum conditions (including extraction solvent: 120 MUL of n-octanol; dispersive solvent: 600 MUL of acetone; collecting solvent: 1000 MUL of acetone, sample pH 3; with no salt), limits of detection (LODs), linear dynamic ranges (LDRs) and recoveries (R) were 79-81 ng mL(-1), 0.26-6.9 MUg mL(-1) and 94.1-99.9%, respectively. The obtained results showed that the IS-R-DLLME was a simple, fast and sensitive method with low level consumption of extraction solvent which provides high recovery under the optimum conditions. The present method was applied to investigate the absorption amounts of the mentioned analytes through the determination of the analytes before (in the plant extracts) and after (in the human plasma and urine samples) the consumption which can determine the toxicity levels of the analytes (on the basis of their dosages) in the extracts. PMID- 26802526 TI - Exposure to raccoon polyomavirus (RacPyV) in free-ranging North American raccoons (Procyon lotor). AB - There is evidence that raccoon polyomavirus is causative for neuroglial brain tumors in the western United States. It is unknown if infection is limited to geographic locales where tumors have been reported or is widespread, like human polyomaviruses. We demonstrate raccoons in western, eastern and midwestern states have been exposed to RacPyV by detection of antibodies to capsid protein, VP1. While raccoons in eastern and midwestern states are seropositive, exposure is lower than in the western states. Additionally, across geographic areas seropositivity is higher in older as compared to younger raccoons, similar to polyomavirus exposure in humans. Serum titers are significantly higher in raccoons with tumors compared to raccoons without. Unlike polyomavirus-associated diseases in humans, we did not detect significant sequence variation between tumor and non-tumor tissue in raccoons with tumors compared to those without tumors. This warrants further investigation into co-morbid diseases or genetic susceptibility studies of the host. PMID- 26802528 TI - Leaching of metals from cement under simulated environmental conditions. AB - Leaching of metals from cement under various environmental conditions was measured to evaluate their environmental safety. A cement product containing clinker, which was produced from cement kiln co-processing of hazardous wastes, was solidified and leaching of metals was characterized using the 8-period test. Concentrations and speciation of metals in cements were determined. Effects of ambient environment and particle size on leachability of metals and mineralogical phases of cement mortars were evaluated by use of XRD and SEM. Results indicated that metals in cements were leachable in various media in descending order of: sea water, groundwater and acid rain. Cr, Ni, As, Co and V were leached by simulated sea water, while Cu, Cd, Pb, Zn, Mn, Sb and Tl were not leached in simulated sea water, groundwater or acid rain. When exposed to simulated acid rain or groundwater, amounts of Cr, Ni, As and V leached was inversely proportional to particle size of cement mortar. According to the one-dimensional diffusion equation, Cr was most leachable and the cumulative leached mass was predicted to be 9.6 mg kg(-1) after 20 years. Results of this study are useful in predicting releases of metals from cement products containing ash and clinkers cement kiln co-processing of hazardous wastes, so that they can be safely applied in the environment. PMID- 26802529 TI - Evaluation of response after pre-operative radiotherapy in soft tissue sarcomas; the European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) and Imaging Group recommendations for radiological examination and reporting with an emphasis on magnetic resonance imaging. AB - At present, there is no standardised approach for the radiological evaluation of soft tissue sarcomas following radiotherapy (RT). This manuscript, produced by a European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) and Imaging Group endorsed task force, aims to propose standardisation of magnetic resonance imaging techniques and interpretation after neoadjuvant RT for routine use and within clinical trials. PMID- 26802530 TI - The burden of malignant melanoma--lessons to be learned from Austria. AB - AIM OF STUDY: Incidence rates of melanoma, generated by cancer registries (CRs), are susceptible to reporting inconsistencies due to increasing decentralisation of diagnosis. We therefore independently assessed the burden of melanoma in Austria. METHODS: We collected histopathological reports on melanoma of all patients diagnosed in Austria in 2011. Demographic and clinical characteristics, histopathological tumour stages were assessed. Their regional distributions and incidence rates were analysed and compared with data of national and international CRs. RESULTS: A total of 5246 patients were diagnosed with 1951 in situ and 3295 invasive melanomas in Austria in 2011 (population 8.4 million). Age, sex and anatomic distribution corresponded to findings in other European countries, however, the incidence of 25/100,000 (world age-standardised rate) for invasive melanomas was two-fold higher than published by the Austrian CR (12/100,000). Varying frequencies in diagnosing thin melanomas (<=1 mm; n = 4415) accounted exclusively for significant regional disparities, while advanced tumours (>1 mm; n = 761) were evenly distributed. Western Austria showed the highest rates (36/100,000). Patients from eastern Austria whose melanomas were diagnosed in laboratories in western Austria (n = 76) showed significantly higher proportions of in-situ lesions (n = 43; 57%) compared to those whose tumours were diagnosed in eastern Austria (n = 4014; in-situ = 1369; 34%) (p < 0.0001). CONCLUSIONS: In Austria, the melanoma burden and its potential socio-economic implications are significantly underestimated. Similarities of incidences indicate this could affect other European countries with well-established CRs and compromise international comparability of data. Austrian regional disparities suggest overdiagnosis of thin melanomas due to the variability of pathologists' thresholds for the diagnosis of early stage tumours. PMID- 26802532 TI - Combination epigenetic and immunotherapy overcomes resistance to monoclonal antibodies in hematologic malignancies: A new therapeutic approach. AB - We recently reported that addition of epigenetic agents could overcome resistance of leukemic cells to monoclonal antibody-mediated anti-tumor effects in T-cell prolymphocytic leukemia. We also reported that epigenetic agents could induce expression of the CD30 gene, thus providing a therapeutic target for the antibody drug conjugate brentuximab vedotin. Here we discuss these findings and their generality to treatment of other hematologic and solid malignancies. PMID- 26802531 TI - Effects of neuromuscular reeducation on hip mechanics and functional performance in patients after total hip arthroplasty: A case series. AB - BACKGROUND: Following total hip arthroplasty, patients demonstrate compensatory movement strategies during activities of daily living such as walking and stair climbing. Movement compensations are important markers of functional decline in older adults and are related to poor functional capacity. Despite increased utilization of hip arthroplasty, persistent movement compensation, and functional performance deficits, no consensus on postoperative rehabilitation exists. Neuromuscular reeducation techniques offer a strategy to improve movement quality by emphasizing hip abductor performance and pelvic stability. This case series illustrates changes in movement strategy around the hip in response to targeted neuromuscular reeducation techniques after hip arthroplasty. METHODS: Five participants received an 8-week exercise program following total hip arthroplasty, emphasizing targeted neuromuscular reeducation techniques hallmarked by specific, weight-bearing exercise to improve hip abductor performance and pelvic stability. Five additional participants were supervised and followed for comparison. FINDINGS: Participants in the neuromuscular reeducation program improved their internal hip abductor moments and vertical ground reaction forces during walking and stair climbing. They also improved their functional performance and hip abductor strength outcomes. INTERPRETATION: Targeted neuromuscular reeducation techniques after total hip arthroplasty provided a positive effect on biomechanical outcomes, functional performance, and muscle strength. Through focused use of the hip abductor muscles, increased internal hip abductor moments were observed. This intervention potentially promotes pelvic stability, and may contribute to improved performance on tasks such as stair climbing, fast walking, and balance. The results suggest that neuromuscular reeducation offers a unique effect on movement strategy and function for patients following total hip arthroplasty. PMID- 26802533 TI - Myasthenia gravis exacerbation associated with pembrolizumab. PMID- 26802534 TI - Who thinks what about e-cigarette regulation? A content analysis of UK newspapers. AB - AIMS: To establish how frequently different types of stakeholders were cited in the UK media debate about e-cigarette regulation, their stances towards different forms of e-cigarette regulation, and what rationales they employed in justifying those stances. METHODS: Quantitative and qualitative content analyses of 104 articles about e-cigarette regulation published in eight UK and three Scottish national newspapers between 1 January 2013 and 31 December 2014. RESULTS: Reporting on e-cigarette regulation grew significantly (P < 0.001) throughout the sample period. Governments and regulatory bodies were the most frequently cited stakeholders and uniformly supported regulation, while other stakeholders did not always support regulation. Arguments for e-cigarette regulation greatly outnumbered arguments against regulation. Regulating purchasing age, restricting marketing and regulating e-cigarettes as medicine were broadly supported, while stakeholders disagreed about prohibiting e-cigarette use in enclosed public spaces. In rationalizing their stances, supporters of regulation cited child protection and concerns about the safety of e-cigarette products, while opponents highlighted the potential of e-cigarettes in tobacco cessation and questioned the evidence base associating e-cigarette use with health harms. CONCLUSIONS: In the UK between 2013 and 2014, governments and tobacco control advocates frequently commented on e-cigarettes in UK-wide and Scottish national newspapers. Almost all commentators supported e-cigarette regulation, but there was disagreement about whether e-cigarette use should be allowed in enclosed public spaces. This appeared to be linked to whether commentators emphasized the harms of vapour and concerns about renormalizing smoking or emphasized the role of e-cigarettes as a smoking cessation aid. PMID- 26802535 TI - Antimicrobial activities of ethanol and butanol fractions of white rose petal extract. AB - White rose (Rosa hybrida) petals were extracted with ethanol (EtOH) or butanol (BuOH), and tested for their antimicrobial activities against two species of Gram positive bacteria, six species of Gram-negative bacteria, and two species of fungi. On in vitro antimicrobial assays, Helicobacter pylori and Propionibacterium acnes were highly susceptible to white rose petal extract (WRPE)-EtOH and WRPE-BuOH, leading to minimal inhibitory concentrations of 100 and 10 MUg/mL for H. pylori and 400 and 40 MUg/mL for P. acnes, respectively. In in vivo experiments, C57BL/6 mice were infected with H. pylori by intragastric inoculation (1 * 10(8) CFU/mouse) 3 times, and orally treated twice a day for 14 days with WRPE-EtOH and WRPE-BuOH. On a CLO kit assay, 200 mg/kg of WRPE-EtOH fully eliminated the bacteria from the gastric mucosa, and the effect of 100 mg/kg of ethanol fraction was similar to pantoprazole (30 mg/kg), displaying 75% elimination. WRPE-BuOH was more effective, exhibiting 75% elimination at 20 mg/kg. The CLO test results were confirmed by bacterial identification. WRPE-EtOH and WRPE-BuOH inhibited the growth of various bacteria and fungi, and in particular, they effectively killed H. pylori and eliminated the bacteria from the mouse stomach. The results indicate that WRPE-EtOH and WRPE-BuOH could be good candidates for the elimination of H. pylori. PMID- 26802537 TI - Viral vector mediated continuous expression of interleukin-10 in DRG alleviates pain in type 1 diabetic animals. AB - Painful diabetic neuropathy is a common and difficult to treat complication of diabetes. A growing body of evidence implicates the role of inflammatory mediators in the damage to the peripheral axons and in the pathogenesis of neuropathic pain. Increased expression of pro-inflammatory cytokines such as interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha in the peripheral nervous system suggests the possibility of change in pain perception in diabetes. In this study we investigated that continuous delivery of IL10 in the nerve fibers achieved by HSV vector mediated transduction of dorsal root ganglion (DRG) in animals with Type 1 diabetes, blocks the nociceptive and stress responses in the DRG neurons by reducing IL1beta expression along with inhibition of phosphorylation of p38 MAPK (mitogen-activated protein kinase) and protein kinase C (PKC). The continuous expression of IL10 also alters Toll like receptor (TLR)-4 expression in the DRG with increased expression of heat shock protein (HSP)-70 in conjunction with the reduction of pain. Taken together, this study suggests that macrophage activation in the peripheral nervous system may be involved in the pathogenesis of pain in Type 1 diabetes and therapeutic benefits of HSV mediated local expression of IL10 in the DRG with the reduction of a number of proinflammatory cytokines, subsequently inhibits the development of painful neuropathy along with a decrease in stress associated markers in the DRG. This basic and preclinical study provides an important evidence for a novel treatment strategy that could lead to a clinical trial for what is currently a treatment resistant complication of diabetes. PMID- 26802536 TI - Expression and alternative splicing of classical and nonclassical MHCI genes in the hippocampus and neuromuscular junction. AB - The major histocompatibility complex class I (MHCI) is a large gene family, with over 20 members in mouse. Some MHCIs are well-known for their critical roles in the immune response. Studies in mice which lack stable cell-surface expression of many MHCI proteins suggest that one or more MHCIs also play unexpected, essential roles in the establishment, function, and modification of neuronal synapses. However, there is little information about which genes mediate MHCI's effects in neurons. In this study, RT-PCR was used to simultaneously assess transcription of many MHCI genes in regions of the central and peripheral nervous system where MHCI has a known or suspected role. In the hippocampus, a part of the CNS where MHCI regulates synapse density, synaptic transmission, and plasticity, we found that more than a dozen MHCI genes are transcribed. Single-cell RT-PCR revealed that individual hippocampal neurons can express more than one MHCI gene, and that the MHCI gene expression profile of CA1 pyramidal neurons differs significantly from that of CA3 pyramidal neurons or granule cells of the dentate gyrus. MHCI gene expression was also assessed at the neuromuscular junction (NMJ), a part of the peripheral nervous system (PNS) where MHCI plays a role in developmental synapse elimination, aging-related synapse loss, and neuronal regeneration. Four MHCI genes are expressed at the NMJ at an age when synapse elimination is occurring in three different muscles. Several MHCI mRNA splice variants were detected in hippocampus, but not at the NMJ. Together, these results establish the first profile of MHCI gene expression at the developing NMJ, and demonstrate that MHCI gene expression is under tight spatial and temporal regulation in the nervous system. They also identify more than a dozen MHCIs that could play important roles in regulating synaptic transmission and plasticity in the central and peripheral nervous systems. PMID- 26802538 TI - Spectra, energy levels, and energy transition of lanthanide complexes with cinnamic acid and its derivatives. AB - High resolution spectra and luminescent lifetimes of 6 europium(III)-cinnamic acid complex {[Eu2L6(DMF)(H2O)].nDMF.H2O}m (L=cinnamic acid I, 4-methyl-cinnamic acid II, 4-chloro-cinnamic acid III, 4-methoxy-cinnamic acid IV, 4-hydroxy cinnamic acid V, 4-nitro-cinnamic acid VI; DMF=N, N-dimethylformamide, C3H7NO) were recorded from 8 K to room temperature. The energy levels of Eu(3+) in these 6 complexes are obtained from the spectra analysis. It is found that the energy levels of the central Eu(3+) ions are influenced by the nephelauxetic effect, while the triplet state of ligand is lowered by the p-pi conjugation effect of the para-substituted functional groups. The best energy matching between the ligand triplet state and the central ion excited state is found in complex I. While the other complexes show poorer matching because the gap of (5)D0 and triplet state contracts. PMID- 26802539 TI - Fluorescence sensing of phosdrin pesticide by the luminescent Eu(III)- and Tb(III)-bis(coumarin-3-carboxylic acid) probes. AB - Luminescence quenching of the Eu(III)- and Tb(III)-bis (coumarin-3-carboxylic acid) (Ln(III)-(CCA)2) probes has been studied in the presence of organophosphorus or organochlorine pesticides; Phosdrin (P1), Malathion (P2), Profenofos (P3), Formothion (P4), Heptachlor (P5), and Endosulfan (P6). The luminescence intensity of lanthanide complex probes Ln(III)-(CCA)2 decreases as the concentration of the Phosdrin pesticide increases, while the other investigated pesticides have no significant influence on the lanthanide fluorescent intensities. It is observed that the quenching of Eu(III) and Tb(III) coumarin-3-carboxylic acid by Phosdrin proceeds via static quenching processes according to Stern-Volmer plot. The binding constants (K) and the thermodynamic parameters of the interaction of Ln(III)-(CCA)2 with Phosdrin have been determined. A direct method for the determination of the Phosdrin in ethanol has been developed based on the luminescence changes of the Ln(III)-(CCA)2-phosdrin ternary complexes. The detection limits of P1 were 6.28 and 1.07 MUM in case of Eu(III) and Tb(III)-complex, respectively. The influence of various interfering species on the detection of P1 has been investigated to assess the analytical applicability of the method. The new method was applied to determine the Phosdrin pesticide in different types of water samples. PMID- 26802541 TI - Characterization of light-dependent regulation of state transitions in gymnosperms. AB - The goal of this study was to characterize the light-dependent regulation of state transitions in gymnosperms. Two species of conifer were examined: eastern white pine (Pinus strobus L.) and white spruce [Picea glauca (Moench) Voss], as well as the angiosperm pumpkin (Cucurbita pepo L. subsp. pepo). Both diurnal time courses in the field and manipulated light experiments in growth chambers were conducted. Results from chlorophyll fluorescence analysis indicated that pumpkin was able to use a larger fraction of absorbed light to drive photochemistry and retain a lower reduction state at a given light intensity relative to the conifers. Results from western blots using anti-phosphothreonine demonstrate that in field conditions, conifers maintained higher light-harvesting complex II (LHCII) phosphorylation than pumpkin; however, this was likely due to a more variable light environment. Manipulated light experiments showed that general patterns of light-dependent LHCII phosphorylation were similar in conifers and pumpkin, with low levels of LHCII phosphorylation occurring in darkness and maximal levels occurring in low light conditions. However, high light-dependent dephosphorylation of LHCIII appears to be regulated differently in conifers, with conifers maintaining phosphorylation of LHCII proteins at higher excitation pressure compared with pumpkin. Additionally, spruce needles maintained relatively high phosphorylation of LHCII even in very high light conditions. Our results suggest that this difference in dephosphorylation of LHCII may be due to differences in the stromal redox status in spruce relative to pine and pumpkin. PMID- 26802542 TI - Thermostable beta-galactosidases for the synthesis of human milk oligosaccharides. AB - Human milk oligosaccharides (HMOs) designate a unique family of bioactive lactose based molecules present in human breast milk. Using lactose as a cheap donor, some beta-galactosidases (EC 3.2.1.23) can catalyze transgalactosylation to form the human milk oligosaccharide lacto-N-neotetraose (LNnT; Gal-beta(1,4)-GlcNAc beta(1,3)-Gal-beta(1,4)-Glc). In order to reduce reaction times and be able to work at temperatures, which are less welcoming to microbial growth, the current study investigates the possibility of using thermostable beta-galactosidases for synthesis of LNnT and N-acetyllactosamine (LacNAc; Gal-beta(1,4)-GlcNAc), the latter being a core structure in HMOs. Two hyperthermostable GH 1 beta galactosidases, Ttbeta-gly from Thermus thermophilus HB27 and CelB from Pyrococcus furiosus, were codon-optimized for expression in Escherichia coli along with BgaD-D, a truncated version of the GH 42 beta-galactosidase from Bacillus circulans showing high transgalactosylation activity at low substrate concentrations. The three beta-galactosidases were compared in the current study in terms of their transgalactosylation activity in the formation of LacNAc and LNnT. In all cases, BgaD-D was the most potent transgalactosidase, but both thermostable GH 1 beta-galactosidases could catalyze formation of LNnT and LacNAc, with Ttbeta-gly giving higher yields than CelB. The thermal stability of the three beta-galactosidases was elucidated and the results were used to optimize the reaction efficiency in the formation of LacNAc, resulting in 5-6 times higher reaction yields and significantly shorter reaction times. PMID- 26802540 TI - Fruit load governs transpiration of olive trees. AB - We tested the hypothesis that whole-tree water consumption of olives (Olea europaea L.) is fruit load-dependent and investigated the driving physiological mechanisms. Fruit load was manipulated in mature olives grown in weighing drainage lysimeters. Fruit was thinned or entirely removed from trees at three separate stages of growth: early, mid and late in the season. Tree-scale transpiration, calculated from lysimeter water balance, was found to be a function of fruit load, canopy size and weather conditions. Fruit removal caused an immediate decline in water consumption, measured as whole-plant transpiration normalized to tree size, which persisted until the end of the season. The later the execution of fruit removal, the greater was the response. The amount of water transpired by a fruit-loaded tree was found to be roughly 30% greater than that of an equivalent low- or nonyielding tree. The tree-scale response to fruit was reflected in stem water potential but was not mirrored in leaf-scale physiological measurements of stomatal conductance or photosynthesis. Trees with low or no fruit load had higher vegetative growth rates. However, no significant difference was observed in the overall aboveground dry biomass among groups, when fruit was included. This case, where carbon sources and sinks were both not limiting, suggests that the role of fruit on water consumption involves signaling and alterations in hydraulic properties of vascular tissues and tree organs. PMID- 26802543 TI - Wheezing recognition algorithm using recordings of respiratory sounds at the mouth in a pediatric population. AB - BACKGROUND: Respiratory diseases in children are a common reason for physician visits. A diagnostic difficulty arises when parents hear wheezing that is no longer present during the medical consultation. Thus, an outpatient objective tool for recognition of wheezing is of clinical value. METHOD: We developed a wheezing recognition algorithm from recorded respiratory sounds with a Smartphone placed near the mouth. A total of 186 recordings were obtained in a pediatric emergency department, mostly in toddlers (mean age 20 months). After exclusion of recordings with artefacts and those with a single clinical operator auscultation, 95 recordings with the agreement of two operators on auscultation diagnosis (27 with wheezing and 68 without) were subjected to a two phase algorithm (signal analysis and pattern classifier using machine learning algorithms) to classify records. RESULTS: The best performance (71.4% sensitivity and 88.9% specificity) was observed with a Support Vector Machine-based algorithm. We further tested the algorithm over a set of 39 recordings having a single operator and found a fair agreement (kappa=0.28, CI95% [0.12, 0.45]) between the algorithm and the operator. CONCLUSIONS: The main advantage of such an algorithm is its use in contact-free sound recording, thus valuable in the pediatric population. PMID- 26802544 TI - Inferring patterns in mitochondrial DNA sequences through hypercube independent spanning trees. AB - Given a graph G, a set of spanning trees rooted at a vertex r of G is said vertex/edge independent if, for each vertex v of G, v?r, the paths of r to v in any pair of trees are vertex/edge disjoint. Independent spanning trees (ISTs) provide a number of advantages in data broadcasting due to their fault tolerant properties. For this reason, some studies have addressed the issue by providing mechanisms for constructing independent spanning trees efficiently. In this work, we investigate how to construct independent spanning trees on hypercubes, which are generated based upon spanning binomial trees, and how to use them to predict mitochondrial DNA sequence parts through paths on the hypercube. The prediction works both for inferring mitochondrial DNA sequences comprised of six bases as well as infer anomalies that probably should not belong to the mitochondrial DNA standard. PMID- 26802545 TI - Design, synthesis and anti-HIV evaluation of novel diarylpyridine derivatives targeting the entrance channel of NNRTI binding pocket. AB - The development of novel NNRTIs with activity against variants of HIV-1RT is crucial for overcoming treatment failure. In the present study, a series of novel 6-substituted diarylpyridine derivatives targeting the entrance channel of the NNIBP of RT were designed through a molecular hybridization strategy. Encouragingly, these new diarylpyridine derivatives were found to be active against wild-type (WT) HIV-1 with an EC50 values ranging from 0.035 MUM to 1.99 MUM. Nearly half of them exhibited more potent inhibitory activities in cellular assays than the control drug nevirapine (NVP). Notably, three most promising compounds If (EC50 = 35 nM), Ia (EC50 = 43 nM) and IIa (EC50 = 41 nM) showed high potency against WT and were comparable to the reference drug delavirdine (DLV) (EC50 = 33 nM). Moreover, compounds Ib, IIb and IIh displayed effective activity against the most common clinically observed single and double-mutated HIV-1 strains in micromolar concentrations. In particular, the inhibition of IIb against the K103N mutation (EC50 = 49 nM), which confers resistance to a wide variety of NNRTIs, was about 140 times more effective than NVP (EC50 = 6.78 MUM), 50 times more than DLV (EC50 = 2.48 MUM) and about 3 times more than EFV (EC50 = 0.12 MUM), indicating that the newly designed compounds have great potential to be further developed as new anti-HIV-1 agents. Preliminary structure-activity relationships (SARs) and molecular modeling of the new diarylpyridine derivatives were discussed in detail. PMID- 26802546 TI - A comparison of novel organoiridium(III) complexes and their ligands as a potential treatment for prostate cancer. AB - A range of 1,4-substituted 2-pyridyl-N-phenyl triazoles were synthesised and evaluated for their antiproliferative properties against lymph node cancer of the prostate (LNCaP) and bone metastasis of prostate cancer (PC-3) cells. Excellent to-low IC50 values were determined (5.6-250 MUM), and a representative group of 4 ligands were then complexed to iridium(III) giving highly luminescent species. Re evaluation of these compounds against both cell lines was then undertaken and improved potency (up to 72-fold) was observed, giving IC50 values of 0.36-11 MUM for LNCaP and 0.85-5.9 MUM for PC-3. Preliminary screens for in vivo toxicity were conducted using a zebrafish model showing a wide range of induced toxicity depending of the compound evaluated. Apoptosis and Caspase-3 levels were also determined and showed no statistical difference between some of the treated specimens and the controls. This study may identify novel therapeutic agents for advanced stage of prostate cancer in humans. PMID- 26802547 TI - Parathyroid hormone(1-34) exhibits more comprehensive effects than celecoxib in cartilage metabolism and maintaining subchondral bone micro-architecture in meniscectomized guinea pigs. AB - OBJECTIVE: To evaluate the effects of PTH(1-34) on cartilage, subchondral bone mass and structure in medial meniscectomized guinea pigs and compare them to those of celecoxib (CLX). METHOD: Forty-eight 3-month-old male Hartley albino guinea pigs received either sham or medial meniscectomy (MNX) operations. One week after the procedure, meniscectomized animals began 12 weeks of treatment by oral administration of CLX (20 mg/kg, daily), subcutaneous injection of PTH (1 34) (24 MUg/kg, 5 days/week), or normal saline for MNX group. All animals were euthanized 12 weeks later, cartilage degeneration and subchondral bone micro architecture was analyzed. RESULTS: OARSI scores indicated cartilage degeneration was partially inhibited by either CLX or PTH(1-34). Cartilage was significantly thicker in PTH(1-34)-treated animals than in CLX-treated animals. Both CLX and PTH(1-34) treatment were associated with lower ADAMTS-4 and periostin expression than MNX. MMP-13 expression in PTH(1-34) group was significantly lower than that in CLX group. However, AGG expression and the ratio of Col-II/MMP-13 expression in PTH(1-34) group were significantly higher than in the CLX group. Micro-CT analysis showed BMD, BV/TV, and Tb.Th levels to be significantly lower in the MNX group and CLX groups than in the sham group, but these parameters were significantly higher in the PTH(1-34) group than in either the MNX group or CLX group. CONCLUSIONS: Both CLX and PTH(1-34) exhibits protective effects on cartilage degeneration in meniscectomized guinea pigs. However, PTH(1-34) exhibited superior performance to CLX not only in metabolism of cartilage tissue but also in maintenance of subchondral bone micro-architecture. PMID- 26802548 TI - Multiple P-values and Bonferroni correction. PMID- 26802549 TI - Incorporating Patient Perspectives and Priorities into Clinical Trial Design. PMID- 26802550 TI - Hydration induced material transfer in membranes of osmotic pump tablets measured by synchrotron radiation based FTIR. AB - Osmotic pump tablets are reliable oral controlled drug delivery systems based on their semipermeable membrane coating. This research used synchrotron radiation based Fourier transform infrared (SR-FTIR) microspectroscopy and imaging to investigate the hydration induced material transfer in the membranes of osmotic pump tablets. SR-FTIR was applied to record and map the chemical information of a micro-region of the membranes, composed of cellulose acetate (CA, as the water insoluble matrix) and polyethylene glycol (PEG, as the soluble pore forming agent and plasticizing agent). The microstructure and chemical change of membranes hydrated for 0, 5, 10 and 30min were measured using SR-FTIR, combined with scanning electronic microscopy and atom force microscopy. The SR-FTIR microspectroscopy results indicated that there was a major change at the absorption range of 2700-3100cm(-1) in the membranes after different periods of hydration time. The absorption bands at 2870-2880cm(-1) and 2950-2960cm(-1) were assigned to represent CA and PEG, respectively. The chemical group signal distribution illustrated by the ratio of PEG to CA demonstrated that the trigger of drug release in the preliminary stage was due to the rapid transfer of PEG into liquid medium with a sharp decrease of PEG in the membranes. The SR-FTIR mapping results have demonstrated the hydration induced material transfer in the membranes of osmotic pump tablets and enabled reassessment of the drug release mechanism of membrane controlled osmotic pump systems. PMID- 26802551 TI - Quercetin derivative induces cell death in glioma cells by modulating NF-kappaB nuclear translocation and caspase-3 activation. AB - Treated glioblastoma multiforme (GBM) patients only survive 6 to 14months after diagnosis; therefore, the development of novel therapeutic strategies to treat gliomas remains critically necessary. Considering that phenolic compounds, like quercetin, have the potential to be used in the chemotreatment of gliomas and that some flavonoids exhibit the ability to cross the BBB, in the present study, we investigated the antitumor effect of flavonoids (including chalcones, flavones, flavanones and flavonols). Initially their activities were tested in C6 glioma cells screened using the MTT method, resulting in the selection of chalcone 2 whose feasibility was confirmed by a Trypan Blue exclusion assay in the low MUM range on C6 glioma cells. Cell cycle and apoptotic death analyses on C6 glioma cells were also performed, and chalcone 2 increased the apoptosis of the cells but did not alter the cell cycle progression. In addition, treatments with these two compounds were not cytotoxic to hippocampal organotypic cultures, a model of healthy neural cells. Furthermore, the results indicated that 2 induced apoptosis by inhibition of NF-kappaB and activation of active caspase-3 in glioma cells, suggesting that it is a potential prototype to develop new treatments for GBM in the future. PMID- 26802553 TI - The physiological performance and immune response of juvenile turbot (Scophthalmus maximus) to nitrite exposure. AB - Nitrite (NO(2-)) is the most common toxic nitrogenous compound in aquatic environment. The aim of the present study was to investigate the effects of nitrite physiological performance and immune response of turbot. Fish were exposed to 0, 0.02, 0.08, 0.4 and 0.8 mM nitrite for 96 h. After 0, 24, 48 and 96 h of exposure, blood were collected to measure the levels of glutamate pyruvate transaminase (GPT), glutamate oxalate transaminase (GOT), alkaline phosphatase (ALP), total protein (TP), albumin (Alb), complement C3 (C3), complement C4 (C4), immunoglobulin M (IgM) and lysozyme (LYS); gill samples were taken to analyze mRNA levels of LYS, heat shock protein 70 (HSP 70), heat shock protein 90 (HSP 90), metallothionein (MT), toll-like receptor 3 (TLR-3), tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta) and insulin-like growth factor I (IGF-I). The results showed that nitrite (0.4 and/or 0.8mM) significantly increased the levels of GPT, GOT, ALP, C3 and C4, reduced the levels of IgM and LYS, up-regulated the gene expressions of HSP 70, HSP 90, MT, TLR-3, TNF-alpha and IL-1beta, and down-regulated the gene expressions of LYS and IGF-1 after 48 and 96 h of exposure. Based on the results, it can be concluded that high level nitrite exposure results in dysfunction of the blood physiology and immunity in turbot. Further, this study will be helpful to understand the mechanism of aquatic toxicology induced by nitrite in marine fish. PMID- 26802552 TI - Carbon nanotubes' surface chemistry determines their potency as vaccine nanocarriers in vitro and in vivo. AB - Carbon nanotubes (CNTs) have shown marked capabilities in enhancing antigen delivery to antigen presenting cells. However, proper understanding of how altering the physical properties of CNTs may influence antigen uptake by antigen presenting cells, such as dendritic cells (DCs), has not been established yet. We hypothesized that altering the physical properties of multi-walled CNTs (MWNTs) antigen conjugates, e.g. length and surface charge, can affect the internalization of MWNT-antigen by DCs, hence the induced immune response potency. For this purpose, pristine MWNTs (p-MWNTs) were exposed to various chemical reactions to modify their physical properties then conjugated to ovalbumin (OVA), a model antigen. The yielded MWNTs-OVA conjugates were long MWNT OVA (~386nm), bearing net positive charge (5.8mV), or short MWNTs-OVA (~122nm) of increasing negative charges (-23.4, -35.8 or -39mV). Compared to the short MWNTs OVA bearing high negative charges, short MWNT-OVA with the lowest negative charge demonstrated better cellular uptake and OVA-specific immune response both in vitro and in vivo. However, long positively-charged MWNT-OVA showed limited cellular uptake and OVA specific immune response in contrast to short MWNT-OVA displaying the least negative charge. We suggest that reduction in charge negativity of MWNT-antigen conjugate enhances cellular uptake and thus the elicited immune response intensity. Nevertheless, length of MWNT-antigen conjugate might also affect the cellular uptake and immune response potency; highlighting the importance of physical properties as a consideration in designing a MWNT-based vaccine delivery system. PMID- 26802554 TI - Comprehensive physiology and toxicology of ecdysogens--The metabolically activated porphyrin-ecdysteroid complexes in insects. AB - The polyhydroxylated derivatives of 6-keto,7-dehydrocholesterol (ecdysone, ecdysteroids, Ecd) are natural compounds widely distributed in plants. They exhibit strong anabolic, vitamin D-like, pharmacological effects in vertebrate animals and in the human body. In the larval stages of insects, injections of pure Ecd cause serious pathophysiological, "hyperecdysonic" syndromes associated with neuromuscular paralysis, premature cuticular apolysis and complete inhibition of ecdysis. Ecds do not penetrate insect cuticle. For this reason, all previous attempts to induce ecdysone responses by topical applications of Ecd failed. In this work, we tried to induce the topical effects of Ecd by preparation of more lipophilic complexes, with 2 or 4 molecules of 20 hydroxyecdysone (E20) attached to a relatively large nucleus of the porphyrin. The resulting porphyrin-E20 complexes (ecdysogens) have been subjected to standardised assays for ecdysone activity in the ligatured larvae ("dauerlarvae") of the greater waxmoth (Galleria mellonella). Similarly like the free E20 alone, porphyrin-E20 complexes had no effect when applied on the body surface or administered in the larval diet. When injected, however, they exhibited delayed effects, but the adverse ("hyperecdysonic") pathophysiological syndromes were reduced or abolished. It is concluded, therefore, that the replacement of pathophysiological, precocious or "hyperecdysonic" moults by the larval-pupal transformation, was due to successive metabolic liberation of the biologically active, free E20 from the porphyrin-E20 complex. The biological status of Ecd does not agree with their definition as the prothoracic gland (PG) hormone of insects, nor with the assumptions about a growth hormone of plants. A possibility that the most important status of Ecd may depend on the pharmacological properties of a sterolic D6 vitamin has been discussed. PMID- 26802555 TI - Molecular imaging of dopamine transporters. AB - The dopamine transporter (DAT) is responsible for clearance of dopamine from the synaptic cleft after its release. Imaging DAT availability provides a measure of dopamine terminal function and a method for detecting the striatal dopamine terminal dysfunction present in idiopathic Parkinson's disease (PD) and atypical neurodegenerative parkinsonian disorders such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). DAT imaging with positron emission tomography (PET) or single photon emission computed tomography (SPECT) can be used to support or refute a diagnosis of dopamine deficient parkinsonism in cases where this is unclear and rationalise a trial of dopamine replacement agents as therapy. It can also detect subclinical dopaminergic dysfunction when present in subjects at risk for PD such as relatives of patients, susceptibility gene mutation carriers, and subjects with late onset hyposmia or sleep disorders. The presence of normal DAT availability on imaging can help categorise "subjects without evidence of dopamine deficiency" (SWEDDs) who on occasion mimic PD and include dystonic tremors, drug-induced and psychogenic parkinsonism in their ranks. Reduced levels of baseline striatal DAT availability on PET or SPECT scanning, however, should be regarded as supportive rather than diagnostic of dopamine deficient parkinsonism. PMID- 26802556 TI - Advances in the development of tau PET radiotracers and their clinical applications. AB - Alzheimer's disease and other neurodegenerative dementias belong to the family of tauopathies. These diseases are characterized by the deposition of insoluble tau aggregates possessing an enriched beta-sheet structure. In vivo imaging of the tau deposits by positron emission tomography (PET) will facilitate the early and accurate diagnosis of these diseases, tracking of disease progression, assessment of disease severity, and prediction of disease prognosis. Furthermore, this technology is expected to play a vital role in the monitoring of treatment outcomes and in the selection of patients for the therapeutic trials of anti dementia drugs. Recently, several tau PET tracers have been successfully developed and demonstrated as having high binding affinity and selectivity to tau protein deposits. Recent clinical studies using these tracers have demonstrated significant tracer retention in sites susceptible to tau deposition in Alzheimer's disease, as well as correlations with the disease severity and cognitive impairment in cases with dementia. These tracers, thus, have the potential to effectively diagnose the tauopathies. Further longitudinal assessment will clarify the effect of the tau deposition on the neurodegenerative process and cognitive decline and the interaction of tau with amyloid-beta in the human brain. PMID- 26802557 TI - Design, synthesis, and in vitro biological evaluation of novel 6-methyl-7 substituted-7-deaza purine nucleoside analogs as anti-influenza A agents. AB - Among many subtypes of influenza A viruses, influenza A(H1N1) and A(H3N2) subtypes are currently circulating among humans (WHO report 2014-15). Therapeutically, the emergence of viral resistance to currently available drugs (adamantanes and neuraminidase inhibitors) has heightened alarms for developing novel drugs that could address diverse targets in the viral replication cycle in order to improve treatment outcomes. To this regard, the design and synthesis of nucleoside analog inhibitors as potential anti-influenza A agents is a very active field of research nowadays. In this study, we designed and synthesized a series of hitherto unknown 6-methyl-7-substituted-7-deaza purine nucleoside analogs, and evaluated for their biological activities against influenza A virus strains, H1N1 and H3N2. From the viral inhibition assay, we identified some effective compounds, among which, compounds 5x (IC50 = 5.88 MUM and 6.95 MUM for H1N1 and H3N2, respectively) and 5z (IC50 = 3.95 MUM and 3.61 MUM for H1N1 and H3N2, respectively) demonstrated potent anti-influenza A activity. On the basis of selectivity index, we conceive that compound 5x may serve as a chemical probe of interest for further lead optimization studies with a general aim of developing novel and effective anti-influenza A virus agents. PMID- 26802558 TI - Antiviral activity of SA-2 against influenza A virus in vitro/vivo and its inhibition of RNA polymerase. AB - A target-free and cell-based approach was applied to evaluate the anti-influenza properties of six newly synthesized benzoic acid derivatives. SA-2, the ethyl 4 (2-hydroxymethyl-5-oxopyrrolidin-1-yl)-3-[3-(3-methylbenzoyl)-thioureido] benzoate (compound 2) was screened as a potential drug candidate. In a cytopathic effect assay, SA-2 dose dependently inhibited H1N1, H3N2 and the oseltamivir resistant mutant H1N1-H275Y influenza viruses in both virus-infected MDCK and A549 cells, with 50% effective concentrations (EC50) in MDCK cells of 9.6, 19.2 and 19.8 MUM respectively, and 50% cytotoxic concentration (CC50) of 444.5 MUM, showing competitive antiviral activity with oseltamivir in vitro. Orally administered SA-2 effectively protected mice infected with lethal doses of H1N1 or oseltamivir-resistant strain H1N1-H275Y, conferring 70% or 50% survival at a dosage of 100 mg/kg/d, reducing body weight loss, alleviating the influenza induced acute lung injury, and reducing lung virus titer. Mechanistic studies showed that SA-2 efficiently inhibited the activity of RNA polymerase and suppressed NP and M1 levels during viral biosynthesis by interfering with gene transcription without having an obvious influence on virus entry and release. Based on these favourable findings, SA-2, a novel anti-influenza agent, with its potent anti-influenza activity in vitro and in vivo, could be a promising antiviral for the treatment of infection of influenza A viruses, including oseltamivir-resistant mutants. PMID- 26802559 TI - Effects of pollen dilution on infection of Nosema ceranae in honey bees. AB - Multiple stressors are currently threatening honey bee health, including pests and pathogens. Among honey bee pathogens, Nosema ceranae is a microsporidian found parasitizing the western honey bee (Apis mellifera) relatively recently. Honey bee colonies are fed pollen or protein substitute during pollen dearth to boost colony growth and immunity against pests and pathogens. Here we hypothesize that N. ceranae intensity and prevalence will be low in bees receiving high pollen diets, and that honey bees on high pollen diets will have higher survival and/or increased longevity. To test this hypothesis we examined the effects of different quantities of pollen on (a) the intensity and prevalence of N. ceranae and (b) longevity and nutritional physiology of bees inoculated with N. ceranae. Significantly higher spore intensities were observed in treatments that received higher pollen quantities (1:0 and 1:1 pollen:cellulose) when compared to treatments that received relatively lower pollen quantities. There were no significant differences in N. ceranae prevalence among different pollen diet treatments. Interestingly, the bees in higher pollen quantity treatments also had significantly higher survival despite higher intensities of N. ceranae. Significantly higher hypopharyngeal gland protein was observed in the control (no Nosema infection, and receiving a diet of 1:0 pollen:cellulose), followed by 1:0 pollen:cellulose treatment that was inoculated with N. ceranae. Here we demonstrate that diet with higher pollen quantity increases N. ceranae intensity, but also enhances the survival or longevity of honey bees. The information from this study could potentially help beekeepers formulate appropriate protein feeding regimens for their colonies to mitigate N. ceranae problems. PMID- 26802560 TI - Segment-specific Ca(2+) transport by isolated Malpighian tubules of Drosophila melanogaster: A comparison of larval and adult stages. AB - Haemolymph calcium homeostasis in insects is achieved through the regulation of calcium excretion by Malpighian tubules in two ways: (1) sequestration of calcium within biomineralized granules and (2) secretion of calcium in soluble form within the primary urine. Using the scanning ion-selective electrode technique (SIET), basolateral Ca(2+) transport was measured at the distal, transitional, main and proximal tubular segments of anterior tubules isolated from both 3rd instar larvae and adults of the fruit fly Drosophila melanogaster. Basolateral Ca(2+) transport exceeded transepithelial secretion by 800-fold and 11-fold in anterior tubules of larvae and adults, respectively. The magnitude of Ca(2+) fluxes across the distal tubule of larvae and adults were larger than fluxes across the downstream segments by 10 and 40 times, respectively, indicating a dominant role for the distal segment in whole animal Ca(2+) regulation. Basolateral Ca(2+) transport across distal tubules of Drosophila varied throughout the life cycle; Ca(2+) was released by distal tubules of larvae, taken up by distal tubules of young adults and was released once again by tubules of adults ? 168 h post-eclosion. In adults and larvae, SIET measurements revealed sites of both Ca(2+) uptake and Ca(2+) release across the basolateral surface of the distal segment of the same tubule, indicating that Ca(2+) transport is bidirectional. Ca(2+) uptake across the distal segment of tubules of young adults and Ca(2+) release across the distal segment of tubules of older adults was also suggestive of reversible Ca(2+) storage. Our results suggest that the distal tubules of D. melanogaster are dynamic calcium stores which allow efficient haemolymph calcium regulation through active Ca(2+) sequestration during periods of high dietary calcium intake and passive Ca(2+) release during periods of calcium deficiency. PMID- 26802561 TI - Insight into mechanism of lanthanum (III) induced damage to plant photosynthesis. AB - A great deal of literature is available regarding the environmental and ecological effects of rare earth element pollution on plants. These studies have shown that excess lanthanum (La) (III) in the environment can inhibit plant growth and even cause plant death. Moreover, inhibition of plant photosynthesis is known to be one of the physiological bases of these damages. However, the mechanism responsible for these effects is still unclear. In this study, the mechanism of La(III)-induced damage to plant photosynthesis was clarified from the viewpoint of the chloroplast ultrastructure, the contents of chloroplast mineral elements and chlorophyll, the transcription of chloroplast ATPase subunits and chloroplast Mg(2+)-ATPase activity, in which rice was selected as a study object. Following treatment with low level of La(III), the chloroplast ultrastructure of rice was not changed, and the contents of chloroplast mineral elements (Mg, P, K, Ca, Mn, Fe, Ni, Cu, and Zn) increased, but the chlorophyll content did not change significantly. Moreover, the transcription of chloroplast ATPase subunits, chloroplast Mg(2+)-ATPase activity, the net photosynthetic rate and growth indices increased. Following treatment with high levels of La(III), the chloroplast ultrastructure was damaged, chloroplast mineral elements (except Cu and Zn) and chlorophyll contents decreased, and the transcription of chloroplast ATPase subunits, chloroplast Mg(2+)-ATPase activity, the net photosynthetic rate and growth indices decreased. Based on these results, a possible mechanism of La(III)-induced damage to plant photosynthesis was proposed to provide a reference for scientific evaluation of the potential ecological risk of rare earth elements in the environment. PMID- 26802562 TI - Alterations in gene expression levels provide early indicators of chemical stress during Xenopus laevis embryo development: A case study with perfluorooctane sulfonate (PFOS). AB - In the present study, Xenopus laevis embryos were exposed to a range of perfluorooctane sulfonate (PFOS) concentrations (0, 0.5, 6, 12, 24, 48 and 96mg/L) for 96h in laboratorial conditions to establish toxicity along with possible gene expression changes. Mortality and deformities were monitored daily and head-tail length was measured at the end of the assay as an indicator of growth. At 24 and 96h post-exposure (hpe), the mRNA expression levels of the genetic markers involved in general stress responses (hsp70, hsp47, crh-a and ucn1), oxidative stress (cat.2 and sod), lipid metabolism (ppard) and apoptosis (tp53 and bax) were analyzed by RT-qPCR. Malformations were significantly higher in the embryos exposed to the highest PFOS concentration (41.8% to 56.4%) compared to controls (5.5%) at 48, 72 and 96hpe. Growth inhibition was observed in the embryos exposed to PFOS concentrations>=48mg/L. At 24 hpe, a statistically significant up-regulation of genes hsp70, hsp47, ppard, tp53 and bax in relation to controls was found. Similar responses were found for genes hsp70, hsp47, crh a, ucn1, sod and ppard at 96 hpe. Alterations in the mRNA expression levels indicated both a stress response to PFOS exposure during X. laevis embryo development, and alterations in the regulation of oxidative stress, apoptosis, and differentiation. These molecular alterations were detected at an earlier exposure time or at lower concentrations than those producing developmental toxicity. Therefore, these sensitive warning signals could be used together with other biomarkers to supplement alternative methods (i.e. the frog embryo test) for developmental toxicity safety evaluations, and as tools in amphibian risk assessments for PFOS and its potential substitutes. PMID- 26802563 TI - Insights into the equilibrium, kinetic and thermodynamics of nickel removal by environmental friendly Lansium domesticum peel biosorbent. AB - Lansium domesticum peel (LDP), a waste material generated from the fruit consumption, was evaluated as a biosorbent for nickel removal from aqueous media. The effects of dosage, contact time, initial pH, initial concentration and temperature on the biosorption process were investigated in batch experiments. Equilibrium data were fitted by the Langmuir, Freundlich, Temkin and Dubinin Radushkevich models using nonlinear regression method with the best-fit model evaluated based on coefficient of determination (R(2)) and Chi-square (chi(2)). The best-fit isotherm was found to be the Langmuir model exhibiting R(2) very close to unity (0.997-0.999), smallest chi(2) (0.0138-0.0562) and largest biosorption capacity (10.1mg/g) at 30 degrees C. Kinetic studies showed that the initial nickel removal was rapid with the equilibrium state established within 30min. Pseudo-second-order model was the best-fit kinetic model indicating the chemisorption nature of the biosorption process. Further data analysis by the intraparticle diffusion model revealed the involvement of several rate controlling steps such as boundary layer and intraparticle diffusion. Thermodynamically, the process was exothermic, spontaneous and feasible. Regeneration studies indicated that LDP biosorbent could be regenerated using hydrochloric acid solution with up to 85% efficiency. The present investigation proved that LDP having no economic value can be used as an alternative eco friendly biosorbent for remediation of nickel contaminated water. PMID- 26802564 TI - Acute exposure to selenium disrupts associative conditioning and long-term memory recall in honey bees (Apis mellifera). AB - A plethora of toxic compounds - including pesticides, heavy metals, and metalloids - have been detected in honey bees (Apis mellifera) and their colonies. One such compound is selenium, which bees are exposed to by consuming nectar and pollen from flowers grown in contaminated areas. Though selenium is lethal at high concentrations, sublethal exposure may also impair honey bees' ability to function normally. Examining the effect of selenium exposure on learning and memory provides a sensitive assay with which to identify sublethal effects on honey bee health and behavior. To determine whether sublethal selenium exposure causes learning and memory deficits, we used proboscis extension reflex conditioning coupled with recall tests 30min and 24h post-conditioning. We exposed forager honey bees to a single sublethal dose of selenium, and 3h later we used an olfactory conditioning assay to train the bees to discriminate between one odor associated with sucrose-reinforcement and a second unreinforced odor. Following conditioning we tested short- and long-term recall of the task. Acute exposure to as little as 1.8ng of an inorganic form of selenium (sodium selenate) before conditioning caused a reduction in behavioral performance during conditioning. And, exposure to 18ng of either an inorganic form (sodium selenate) or an organic form (methylseleno-l-cysteine) of selenium caused a reduction in the bees' performance during the long-term recall test. These concentrations of selenium are lower than those found in the nectar of plants grown in selenium contaminated soil, indicating that even low-grade selenium toxicity produces significant learning and memory impairments. This may reduce foragers' ability to effectively gather resources for the colony or nurse bees' ability to care for and maintain a healthy colony. PMID- 26802565 TI - Concentrations, diffusive fluxes and toxicity of heavy metals in pore water of the Fuyang River, Haihe Basin. AB - While the concentrations of heavy metals in pore water provide important information about their bioavailability, to date few studies have focused on this topic. In this study, pore water in river sediments collected from nine sampling sites (S1-S9) was examined to determine the concentrations, fluxes, and toxicity of heavy metals in the Fuyang River. The results showed that the average concentrations of Cr, Ni, Cu, As, Zn, and Pb in pore water were 17.06, 15.97, 20.93, 19.08, 43.72, and 0.56MUgL(-1), respectively; these concentrations varied as the pore water depth increased. The diffusive fluxes of Cr, Ni, Cu, As, Zn, and Pb were in the following range: (-0.37) to 3.17, (-1.37) to 2.63, (-4.61) to 3.44, 0.17-6.02, (-180.26) to 7.51, and (-0.92) to (-0.29)MUg(m(2)day)(-1), respectively. There was a potential risk of toxicity from Cu to aquatic organisms, as indicated by a value of the Interstitial Water Criteria Toxic Units that exceeded 1.0. Values of the Nemeraw Index were 2.06, 0.48, 0.11, 0.20, 1.11, 1.03, 0.99, 0.88, and 0.89 from S1 to S9, respectively. Only S1 was moderately polluted by heavy metals in pore water. PMID- 26802566 TI - Prognostic value of tumour deposit and perineural invasion status in colorectal cancer patients: a SEER-based population study. AB - AIMS: The definition of tumour deposit (TD) in colorectal cancer (CRC) was changed recently in the American Joint Commission on Cancer (AJCC) Staging Manual, 7th edition. We aimed to examine the prognostic values of the newly defined TD and perineural invasion (PNI) in this population study. METHODS AND RESULTS: We identified the incidental CRC cases with known TD or PNI status in the Surveillance, Epidemiology, and End Results (SEER) programme diagnosed in 2010 and 2011. Kaplan-Meier survival analysis and multivariable Cox proportional hazards models were used to estimate overall survivals (OS) and cancer-specific survival (CSS). We found that 6.71% (2774 of 41 323) of the CRC cases were positive for TD and 9.61% (3970 of 41 215) positive for PNI. In multivariable models, TD- and PNI-positive statuses correlated independently with worse 3-year OS [hazard ratio (HR): 1.68, 95% confidence interval (CI): 1.58-1.80 and HR: 1.24, 95%: CI: 1.16-1.32, respectively] and 3-year CSS (HR: 1.79, 95% CI: 1.65 1.94 and HR: 1.28, 95% CI: 1.18-1.38, respectively, P < 0.001 for all). Other independent prognostic factors included age, T category, N category, tumour location and tumour grade, but not gender. TD and PNI correlated with worse OS in all N categories (P < 0.001 for all). TD-associated HR for 3-year OS increases as the N category becomes lower (1.73 in N2, 2.32 in N1 and 3.24 in N0), while rare (1.4%) TD-positive CRC in N0 category should have been assigned to N1c. CONCLUSIONS: Tumour deposit and PNI correlate independently with worse 3-year OS and CSS. TD appears prognostically more important in the CRC of lower N categories. PMID- 26802567 TI - Amygdala-Hippocampal Phospholipase D (PLD) Signaling As Novel Mechanism of Cocaine-Environment Maladaptive Conditioned Responses. AB - BACKGROUND: Drug-environment associative memory mechanisms and the resulting conditioned behaviors are key contributors in relapse to cocaine dependence. Recently, we reported rat amygdala phospholipase D as a key convergent downstream signaling partner in the expression of cocaine-conditioned behaviors mediated by glutamatergic and dopaminergic pathways. In the present study, 1 of the 2 known upstream serotonergic targets of phospholipase D, the serotonin (5 hydroxytryptamine) 2C receptor, was investigated for its role in recruiting phospholipase D signaling in cocaine-conditioned behaviors altered in the rat amygdala and dorsal hippocampus. METHODS: Using Western-blot analysis, amygdala phospholipase D phosphorylation and total expression of phospholipase D/5 hydroxytryptamine 2C receptor were observed in early (Day-1) and late (Day-14) withdrawal (cocaine-free) states among male Sprague-Dawley rats subjected to 7 day cocaine-conditioned hyperactivity training. Functional studies were conducted using Chinese Hamster Ovary cells with stably transfected human unedited isoform of 5-hydroxytryptamine 2C receptor. RESULTS: Phosphorylation of phospholipase D isoforms was altered in the Day-1 group of cocaine-conditioned animals, while increased amygdala and decreased dorsal hippocampus phospholipase D/5 hydroxytryptamine 2C receptor protein expression were observed in the Day-14 cocaine-conditioned rats. Functional cellular studies established that increased p phospholipase D is a mechanistic response to 5-HT2CR activation and provided the first evidence of a biased agonism by specific 5-hydroxytryptamine 2C receptor agonist, WAY163909 in phospholipase D phosphorylation 2, but not phospholipase D phosphorylation 1 activation. CONCLUSIONS: Phospholipase D signaling, activated by dopaminergic, glutamatergic, and serotonergic signaling, can be a common downstream element recruited in associative memory mechanisms altered by cocaine, where increased expression in amygdala and decreased expression in dorsal hippocampus may result in altered anxiety states and increased locomotor responses, respectively. PMID- 26802569 TI - Health insurance coverage among women of reproductive age before and after implementation of the affordable care act. AB - OBJECTIVES: The Affordable Care Act's expansions to Medicaid and private coverage are of particular importance for women of childbearing age, who have numerous preventive care and reproductive health care needs. STUDY DESIGN: We conducted two national surveys, one in 2012 and one in 2015, collecting information about health insurance coverage and access to care from 8000 women aged 18-39. We examine type of insurance and continuity of coverage between time periods, including poverty status and whether or not women live in a state that expanded Medicaid coverage. RESULTS: The proportion of women who were uninsured declined by almost 40% (from 19% to 12%), though several groups, including US-born and foreign-born Latinas, experienced no significant declines. Among low-income women in states that expanded Medicaid, the proportion uninsured declined from 38% to 15%, largely due to an increase in Medicaid coverage (from 40% to 62%). Declines in uninsurance in nonexpansion states were only marginally significant. CONCLUSIONS: Despite substantial improvements in health insurance coverage, significant gaps remain, particularly in states that have not expanded Medicaid and for Latinas. IMPLICATIONS: This analysis examines changes in insurance coverage that occurred after the Affordable Care Act was implemented. While coverage has improved for many populations, sizeable gaps in coverage remain for Latinas and women in states that did not expand Medicaid. PMID- 26802568 TI - Negative Allosteric Modulators of Metabotropic Glutamate Receptors Subtype 5 in Addiction: a Therapeutic Window. AB - BACKGROUND: Abundant evidence at the anatomical, electrophysiological, and molecular levels implicates metabotropic glutamate receptor subtype 5 (mGluR5) in addiction. Consistently, the effects of a wide range of doses of different mGluR5 negative allosteric modulators (NAMs) have been tested in various animal models of addiction. Here, these studies were subjected to a systematic review to find out if mGluR5 NAMs have a therapeutic potential that can be translated to the clinic. METHODS: Literature on consumption/self-administration and reinstatement of drug seeking as outcomes of interest published up to April 2015 was retrieved via PubMed. The review focused on the effects of systemic (i.p., i.v., s.c.) administration of the mGluR5 NAMs 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP) and 2-Methyl-6-(phenylethynyl)pyridine (MPEP) on paradigms with cocaine, ethanol, nicotine, and food in rats. RESULTS: MTEP and MPEP were found to reduce self-administration of cocaine, ethanol, and nicotine at doses >=1mg/kg and 2.5mg/kg, respectively. Dose-response relationship resembled a sigmoidal curve, with low doses not reaching statistical significance and high doses reliably inhibiting self-administration of drugs of abuse. Importantly, self administration of cocaine, ethanol, and nicotine, but not food, was reduced by MTEP and MPEP in the dose range of 1 to 2mg/kg and 2.5 to 3.2mg/kg, respectively. This dose range corresponds to approximately 50% to 80% mGluR5 occupancy. Interestingly, the limited data found in mice and monkeys showed a similar therapeutic window. CONCLUSION: Altogether, this review suggests a therapeutic window for mGluR5 NAMs that can be translated to the treatment of substance related and addictive disorders. PMID- 26802570 TI - DPD epitope-specific glutamic acid decarboxylase (GAD)65 autoantibodies in children with Type 1 diabetes. AB - AIM: To study whether DPD epitope-specific glutamate decarboxylase autoantibodies are found more frequently in children with milder forms of Type 1 diabetes. METHODS: We prospectively evaluated 75 children with new-onset autoimmune Type 1 diabetes, in whom we collected demographic, anthropometric and clinical data and measured islet autoantibodies. Glutamate decarboxylase 65 autoantibody-positive samples were analysed for epitope specificities using recombinant Fab against the DPD-defined epitope of glutamate decarboxylase 65. RESULTS: After adjustment for age, positive DPD epitope recognition was significantly associated with higher C peptide levels at onset (P = 0.02, r2 =0.21, n = 35), and high DPD recognition in the highest quartile tended to be associated with HbA1c <= 53 mmol/mol (7%) at the last follow-up [mean (sd) follow-up 1.3 (0.4) years; P = 0.07; for the model, P = 0.044, n = 30)]. Age- and sex-adjusted BMI percentile was significantly correlated with recognition of the DPD-defined epitope (P < 0.03, r2 =0.14, n = 34), but this correlation was driven by the older age group (age >= 10 years; P = 0.016, r2 =0.27, n = 21) and was not significant in younger children (P = 0.93, n = 13). There were no independent associations with sex, race/ethnicity, diabetic ketoacidosis, HbA1c , HLA DR3-DQ2/DR4-DQ8 or autoantibody number. CONCLUSIONS: Our findings suggest that recognition of the DPD-defined glutamate decarboxylase 65 autoantibody epitope at Type 1 diabetes onset is directly associated with beta cell function, BMI and age, which supports the hypothesis that immunological factors contribute to the clinical heterogeneity of Type 1 diabetes. Larger studies relating epitope-specific glutamate decarboxylase 65 autoantibody to clinical phenotype in children with Type 1 diabetes are warranted. PMID- 26802572 TI - Simple ossicular chain reconstruction during ear surgery using tragal cartilage: a retrospective clinical study in thirty-one patients: A clinical audit. PMID- 26802571 TI - Microbial diversity and metabolite composition of Belgian red-brown acidic ales. AB - Belgian red-brown acidic ales are sour and alcoholic fermented beers, which are produced by mixed-culture fermentation and blending. The brews are aged in oak barrels for about two years, after which mature beer is blended with young, non aged beer to obtain the end-products. The present study evaluated the microbial community diversity of Belgian red-brown acidic ales at the end of the maturation phase of three subsequent brews of three different breweries. The microbial diversity was compared with the metabolite composition of the brews at the end of the maturation phase. Therefore, mature brew samples were subjected to 454 pyrosequencing of the 16S rRNA gene (bacteria) and the internal transcribed spacer region (yeasts) and a broad range of metabolites was quantified. The most important microbial species present in the Belgian red-brown acidic ales investigated were Pediococcus damnosus, Dekkera bruxellensis, and Acetobacter pasteurianus. In addition, this culture-independent analysis revealed operational taxonomic units that were assigned to an unclassified fungal community member, Candida, and Lactobacillus. The main metabolites present in the brew samples were L-lactic acid, D-lactic acid, and ethanol, whereas acetic acid was produced in lower quantities. The most prevailing aroma compounds were ethyl acetate, isoamyl acetate, ethyl hexanoate, and ethyl octanoate, which might be of impact on the aroma of the end-products. PMID- 26802573 TI - In situ microliter-droplet anodic stripping voltammetry of copper stained on the gold label after galvanic replacement reaction enlargement for ultrasensitive immunoassay of proteins. AB - We report a new protocol for ultrasensitive electrochemical sandwich-type immunosensing, on the basis of signal amplification by gold-label/copper staining, galvanic replacement reactions (GRRs), and in situ microliter-droplet anodic stripping voltammetry (ASV) after an enhanced cathodic preconcentration of copper. First, a sandwich-type immuno-structure is appropriately assembled at a glassy carbon electrode. Second, copper is selectively stained on the catalytic surfaces of second antibody-conjugated Au nanoparticles through CuSO4-ascorbic acid redox reaction, and the GRRs between HAuCl4 and the stained copper are used to amplify the quantity of copper. Finally, the corresponding antigen is determined based on simultaneous chemical-dissolution/cathodic-preconcentration of copper for in-situ ASV analysis directly at the immunoelectrode. Cyclic voltammetry, electrochemical impedance spectroscopy, quartz crystal microbalance and scanning electron microscopy are used for film characterization and/or process monitoring. Under optimized conditions, ultrasensitive analyses of human immunoglobulin G (IgG) and human carbohydrate antigen 125 (CA125) are achieved. The limits of detection are 0.3 fg mL(-1) (equivalent to 7 IgG molecules in the 6 MUL sample employed) for IgG (S/N=3) and 1.3 nU mL(-1) for CA125 (S/N=3), respectively, which are amongst the best reported to date for the two proteins. The theoretical feasibility of such a single-molecule-level amperometric immunoassay is also discussed based on the immunological reaction thermodynamics. PMID- 26802574 TI - Near-infrared fluorescence nanoprobe for enzyme-substrate system sensing and in vitro imaging. AB - Herein we report a simple and sensitive fluorescent sensing platform for phenol and enzyme activity detection based on 3-aminobenzeneboronic acid functionalized CuInS2 QDs (APBA-CuInS2 QDs). APBA were covalently linked to CuInS2 QDs surface to form the APBA-CuInS2 QDs which had a fairly symmetric fluorescence emission peak at 736 nm in the near-infrared spectral region. In the presence of tyrosinase, phenol can be catalyzed the oxidization into catechol, which could reactive toward the boronic acid functional groups of APBA-CuInS2 QDs to form five-membered cyclic esters, leading to the fluorescence quenching of the QDs. The effective fluorescence quenching of APBA-CuInS2 QDs by phenol enabled this proposed nanosensor to sensitively detect the phenol product-related enzyme system, such as acid phosphatase-catalyzed hydrolysis of phenyl phosphate. Thus, the proposed biosensor was utilized for facile, sensitive, and selective detection phenol, tyrosinase and acid phosphatase. The detection limits of phenol, tyrosinase and acid phosphatase reached 0.05 MUmol L(-1), 0.03 U mL(-1) and 6 nU mL(-1) for, respectively. The feasibility of the proposed nanosensor in real samples assay was also studied and satisfactory results were obtained. Meanwhile, using the APBA-CuInS2 QDs fluorescence probe, we successfully performed in vitro imaging of human prostate cancer cells, suggesting the biocompatible sensor has potentially extensive application clinic diagnoses assays. PMID- 26802575 TI - Real-time monitoring of glucose-6-phosphate dehydrogenase activity using liquid droplet arrays and its application to human plasma samples. AB - Glucose-6-phosphate dehydrogenase (G6PD) regulates nicotinamide adenine dinucleotide phosphate (NADPH) levels and is related to the pathogenesis of various diseases, including G6PD deficiency, type 2 diabetes, aldosterone-induced endothelial dysfunction, and cancer. Therefore, a highly sensitive array-based assay for determining quantitative G6PD activity is required. Here, we developed an on-chip G6PD activity assay using liquid droplet fluorescence arrays. Quantitative G6PD activity was determined by calculating reduced resorufin concentrations in liquid droplets. The limit of detection (LOD) of this assay was 0.162 mU/ml (2.89 pM), which is much more sensitive than previous assays. We used our activity assay to determine kinetic parameters, including Michaelis-Menten constants (Km) and maximum rates of enzymatic reaction (Vmax) for NADP(+) and G6P, and half-maximal inhibitory concentrations (IC50). We successfully applied this new assay to determine G6PD activity in human plasma from normal healthy individuals (n=30) and patients with inflammation (n=30). The inflammatory group showed much higher G6PD activities than did the normal group (p<0.001), with a high area under the curve value of 0.939. Therefore, this new activity assay has the potential to be used for diagnosis of G6PD-associated diseases and utilizing kinetic studies. PMID- 26802576 TI - Gonyautoxin 1/4 aptamers with high-affinity and high-specificity: From efficient selection to aptasensor application. AB - Gonyautoxin 1/4 (GTX1/4) are potent marine neurotoxins with significant public health impact. However, the ethical issues and technical defects associated with the currently applied detection methods for paralytic shellfish toxin GTX1/4 are pressing further studies to develop suitable alternatives in a regulatory monitoring system. This work describes the first successful selection, optimization, and characterization of an aptamer that bind with high affinity and specificity to GTX1/4. Compared to the typical MB-SELEX, GO-SELEX, an advanced screening technology, has significant advantages for small molecular aptamer development. Furthermore, we truncated GTX1/4 aptamer and obtained the aptamer core sequence with a higher Kd of 17.7 nM. The aptamer GO18-T-d was then used to construct a label-free and real-time optical BLI aptasensor for the detection of GTX1/4. The aptasensor showed a broad detection range from 0.2 to 200 ng/mL GTX1/4 (linear range from 0.2 to 90 ng/mL), with a low detection limit of 50 pg/mL. Moreover, the aptasensor exhibited a high degree of specificity for GTX1/4 and no cross reactivity to other marine toxins. The aptasensor was then applied to the detection of GTX1/4 in spiked shellfish samples and showed a good reproducibility and stability. We believe that this novel aptasensor offers a promising alternative to traditional analytical methods for the rapid detection of the marine biotoxin GTX1/4. PMID- 26802577 TI - Factors associated with early insulin initiation in Type 2 diabetes: a Canadian cross-sectional study. AB - AIM: To examine the patient characteristics associated with early initiation of insulin after a diagnosis of Type 2 diabetes. METHODS: We analysed cross sectional data from the 2012 Canadian Community Health Survey conducted by Statistics Canada. Multivariable logistic regression was used to explore the association between patient sociodemographic and health status characteristics and initiating insulin within 1 year of a diagnosis of Type 2 diabetes (early insulin use). RESULTS: Weighted estimates for the Canadian population showed that 32% of patients with Type 2 diabetes initiated insulin within 1 year of their diagnosis. Of the insulin initiators, 52% were female and 68% were aged >=60 years. Factors strongly associated with early initiation of insulin were age (60 69 years: adjusted odds ratio 1.89, 95% CI 1.84-1.94; >= 70 years, odds ratio 2.08, 95% CI 2.01-2.15, both vs 40-49 years); smoking (smoker vs never: odds ratio 2.39, 95% CI 2.32-2.46); geography (Western Canada: odds ratio 2.75, 95% CI 2.69-2.81; Quebec: odds ratio 2.20, 95% CI 2.13-2.27, both vs Ontario); mental health (poor vs excellent: odds ratio 1.98, 95% CI 1.92-2.04); BMI (overweight vs normal/underweight: odds ratio 1.63, 95% CI 1.58-1.67); oral antidiabetic medication use (yes vs no: odds ratio 0.66, 95% CI 0.65-0.68); and alcohol use (regular vs non-drinker: odds ratio 0.66, 95% CI 0.65-0.68). CONCLUSION: One third of the study population with Type 2 diabetes initiated insulin within their first year of diagnosis. Age, smoking status, geographical location, mental health, BMI, education, oral antidiabetic medication use, employment, physical activity, language, doctor visits and alcohol consumption were associated with timing of insulin initiation. PMID- 26802578 TI - Maternal and fetal morbidity associated with uterine rupture of the unscarred uterus. PMID- 26802579 TI - Impact of a labor and delivery safety bundle on a modified adverse outcomes index. AB - BACKGROUND: The Obstetrics Adverse Outcomes Index was designed to measure the quality of perinatal care and includes 10 adverse events that may occur at or around the time of delivery. We hypothesized that adverse outcomes in the labor and delivery suite, including hypoxic ischemic encephalopathy, could be decreased with a combination of interventions, even among high-risk pregnancies. OBJECTIVE: The objective of the study was to evaluate the impact of a labor and delivery care bundle on adverse obstetrics outcomes as measured by a modified Obstetrics Adverse Outcomes Index, Weighted Adverse Outcomes Index, and Severity Index. STUDY DESIGN: This is a retrospective cohort study including all women who delivered at our academic, tertiary care institution over a 3 year period of time, before and after the implementation of an intervention to decrease adverse outcomes. Outcome measures consisted of previously reported indices that were modified including the addition of hypoxic ischemic encephalopathy. The adverse outcomes index is a percentage of deliveries with 1 or more adverse events, the weighted adverse outcomes index is the sum of the points assigned to cases with adverse outcomes divided by the number of deliveries, and the severity index is the sum of the adverse outcome scores divided by the number of deliveries with an identified adverse outcome. A segmented regression analysis was utilized to evaluate the differences in the level and trend of each index before and after our intervention using calendar month as the unit of analysis. RESULTS: During the study period, 5826 deliveries met inclusion criteria. Comparing the pre- and postintervention periods, high-risk pregnancy was more common in the postintervention period (73.5% vs 79.4%, P < .001). Overall, there was a decrease in both the Modified Weighted Adverse Outcomes Index (P = .0497) and the Modified Severity Index (P = 0.01) comparing the pre- and postintervention periods; there was no difference in the Modified Adverse Outcomes Index (P = .43). For low-risk pregnancies, there was no significant difference in the levels for any of the measured indices over the study period (P = .61, P = .41, and P = .34 for the Modified Adverse Outcomes Index, Modified Weighted Adverse Outcomes Index, and Modified Severity Index, respectively). Among the high-risk pregnancies, the monthly Modified Weighted Adverse Outcomes Index decreased by 4.2 +/- 1.8 (P = .03). The monthly Modified Severity Index decreased by 53.9 +/- 17.7 points from the pre- to the postintervention periods (P = .01) and was < 50% of the predicted Modified Severity Index had the intervention not been implemented. The cesarean delivery rate was increasing prior to the intervention, but the rate was stable after the intervention, and the absolute rate did not differ between the pre- and the postintervention periods (28.4% vs 30.0%, P = .20). CONCLUSION: Overall and for high-risk pregnancies, the implementation of the labor and delivery care bundle had a positive impact on the Modified Weighted Adverse Outcomes Index and Modified Severity Index but not the Modified Adverse Outcomes Index. PMID- 26802580 TI - Reply. PMID- 26802583 TI - Sexual Function and Fertility of Women with Classic Bladder Exstrophy and Continent Urinary Diversion. AB - PURPOSE: We evaluated the outcome in female patients with classic bladder exstrophy and continent urinary diversion for sexual function and fertility. MATERIALS AND METHODS: We reviewed the medical records of female exstrophy patients who underwent continent urinary diversion in our department between 1969 and 2014. Patients were invited for followup examination and asked to complete questionnaires relating to sexual function, social integration and maternity. RESULTS: Of 38 eligible patients 29 (response rate 76%) with a followup of 22.3 years were included in study. Primary continent urinary diversion was done in 62% of patients and 38% underwent secondary continent urinary diversion after failed reconstruction of the exstrophic bladder. Sexual function as measured by the Female Sexual Function Index was only little affected in all domains except desire. Mean total Female Sexual Function Index score was 28.4 of a possible 36. Of the women 31% were classified as at risk for sexual dysfunction, 72% had a stable relationship, 41% were married and 31% had completed higher education. The incidence of pelvic organ prolapse requiring surgical repair was 38%. A total of 16 healthy children were conceived by 12 patients. The pregnancy rate after primary continent urinary diversion was higher than after secondary diversion. CONCLUSIONS: The sexuality and fertility of female patients with exstrophy after continent urinary diversion appears to be comparable with those in previously reported series of patients in whom the bladder was preserved. Management of sexual function, gynecologic pathologies and fertility should be an active part of long-term followup. PMID- 26802582 TI - Integrative Pathway Analysis of Metabolic Signature in Bladder Cancer: A Linkage to The Cancer Genome Atlas Project and Prediction of Survival. AB - PURPOSE: We used targeted mass spectrometry to study the metabolic fingerprint of urothelial cancer and determine whether the biochemical pathway analysis gene signature would have a predictive value in independent cohorts of patients with bladder cancer. MATERIALS AND METHODS: Pathologically evaluated, bladder derived tissues, including benign adjacent tissue from 14 patients and bladder cancer from 46, were analyzed by liquid chromatography based targeted mass spectrometry. Differential metabolites associated with tumor samples in comparison to benign tissue were identified by adjusting the p values for multiple testing at a false discovery rate threshold of 15%. Enrichment of pathways and processes associated with the metabolic signature were determined using the GO (Gene Ontology) Database and MSigDB (Molecular Signature Database). Integration of metabolite alterations with transcriptome data from TCGA (The Cancer Genome Atlas) was done to identify the molecular signature of 30 metabolic genes. Available outcome data from TCGA portal were used to determine the association with survival. RESULTS: We identified 145 metabolites, of which analysis revealed 31 differential metabolites when comparing benign and tumor tissue samples. Using the KEGG (Kyoto Encyclopedia of Genes and Genomes) Database we identified a total of 174 genes that correlated with the altered metabolic pathways involved. By integrating these genes with the transcriptomic data from the corresponding TCGA data set we identified a metabolic signature consisting of 30 genes. The signature was significant in its prediction of survival in 95 patients with a low signature score vs 282 with a high signature score (p = 0.0458). CONCLUSIONS: Targeted mass spectrometry of bladder cancer is highly sensitive for detecting metabolic alterations. Applying transcriptome data allows for integration into larger data sets and identification of relevant metabolic pathways in bladder cancer progression. PMID- 26802581 TI - Pathophysiology of the cochlear intrastrial fluid-blood barrier (review). AB - The blood-labyrinth barrier (BLB) in the stria vascularis is a highly specialized capillary network that controls exchanges between blood and the intrastitial space in the cochlea. The barrier shields the inner ear from blood-born toxic substances and selectively passes ions, fluids, and nutrients to the cochlea, playing an essential role in the maintenance of cochlear homeostasis. Anatomically, the BLB is comprised of endothelial cells (ECs) in the strial microvasculature, elaborated tight and adherens junctions, pericytes (PCs), basement membrane (BM), and perivascular resident macrophage-like melanocytes (PVM/Ms), which together form a complex "cochlear-vascular unit" in the stria vascularis. Physical interactions between the ECs, PCs, and PVM/Ms, as well as signaling between the cells, is critical for controlling vascular permeability and providing a proper environment for hearing function. Breakdown of normal interactions between components of the BLB is seen in a wide range of pathological conditions, including genetic defects and conditions engendered by inflammation, loud sound trauma, and ageing. In this review, we will discuss prevailing views of the structure and function of the strial cochlear-vascular unit (also referred to as the "intrastrial fluid-blood barrier"). We will also discuss the disrupted homeostasis seen in a variety of hearing disorders. Therapeutic targeting of the strial barrier may offer opportunities for improvement of hearing health and amelioration of auditory disorders. This article is part of a Special Issue entitled . PMID- 26802584 TI - Resection of the Intramural Portion of the Distal Ureter during Transurethral Resection of Bladder Tumors: Predictive Factors for Secondary Stenosis and Development of Upper Urinary Tract Recurrence. AB - PURPOSE: We analyzed the incidence of and predictive factors for ureteral stenosis and recurrent upper urinary tract urothelial carcinoma after resection of tumors located in the intramural portion of the distal ureter. MATERIALS AND METHODS: We retrospectively analyzed the records of 2,317 patients who underwent transurethral resection of bladder tumor for nonmuscle invasive bladder cancer, including 112 (4.83%) with tumors involving the intramural portion of the distal ureter. Multivariate Cox regression analysis was done to determine predictive factors for ureteral stenosis and recurrent urinary tract urothelial carcinoma. RESULTS: At a mean followup of 56 months 17 patients (15.2%) presented with recurrent upper urinary tract urothelial carcinoma and ureteral stenosis had developed in 13 (11.6%). On univariate analysis previous recurrences were associated with both events. On multivariate analysis tumor size 1.5 cm or greater (HR 4.521, p = 0.023) and T1 tumor stage (HR 8.525, p = 0.005) were independent predictive factors for stenosis. Stage T1 in the bladder (HR 7.253, p = 0.001) and carcinoma in situ in the intramural portion of the distal ureter (HR 6.850, p = 0.005) increased the risk of recurrent upper urinary tract urothelial carcinoma. The main study limitation was the lack of information on vesicoureteral reflux due to the retrospective design. CONCLUSIONS: Involvement of the intramural portion of the distal ureter is uncommon. In patients with nonmuscle invasive bladder cancer and involvement of the intramural portion of the distal ureter a stage T1 tumor and a tumor size 1.5 cm or greater are independent predictive factors for distal ureteral stenosis. Moreover, stage T1 and carcinoma in situ in the intramural portion of the distal ureter significantly increase the risk of recurrent upper urinary tract urothelial carcinoma. The urinary tract should be more closely followed in this patient subgroup. PMID- 26802585 TI - Celebrating the Success of an AACN Partnership. PMID- 26802586 TI - Measuring the Success of a Pipeline Program to Increase Nursing Workforce Diversity. AB - The purpose of this study was to understand changes in knowledge and opinions of underserved American Indian and Hispanic high school students after attending a 2 week summer pipeline program using and testing a pre/postsurvey. The research aims were to (a) psychometrically analyze the survey to determine if scale items could be summed to create a total scale score or subscale scores; (b) assess change in scores pre/postprogram; and (c) examine the survey to make suggestions for modifications and further testing to develop a valid tool to measure changes in student perceptions about going to college and nursing as a result of pipeline programs. Psychometric analysis indicated poor model fit for a 1-factor model for the total scale and majority of subscales. Nonparametric tests indicated statistically significant increases in 13 items and decreases in 2 items. Therefore, while total scores or subscale scores cannot be used to assess changes in perceptions from pre- to postprogram, the survey can be used to examine changes over time in each item. Student did not have an accurate view of nursing and college and underestimated support needed to attend college. However students realized that nursing was a profession with autonomy, respect, and honor. PMID- 26802587 TI - Fostering Future Leadership in Quality and Safety in Health Care through Systems Thinking. AB - There is a critical need for leadership in quality and safety to reform today's disparate spectrum of health services to serve patients in complex health care environments. Nurse graduates of degree completion programs (registered nurse bachelor of science in nursing [RN-BSN]) are poised for leadership due to their recent education and nursing practice experience. The authors propose that integration of systems thinking into RN-BSN curricula is essential for developing these much needed leadership skills. The purpose of this article is to introduce progressive teaching strategies to help nurse educators achieve the student competencies described in the second essential of the BSN Essentials document (American Association of Colleges of Nursing, 2009), linking them with the competencies in Quality and Safety Education for Nurses (QSEN; L. Cronenwett et al., 2007) using an author-created model for curricular design, the Systems-level Awareness Model. The Systems Thinking Tool (M. A. Dolansky & S. M. Moore, 2013) can be used to evaluate systems thinking in the RN-BSN curriculum. PMID- 26802588 TI - Hartford Gerontological Nursing Leaders: From Funding Initiative to National Organization. AB - In 2000, the John A. Hartford Foundation established the Building Academic Geriatric Nursing Capacity Program initiative, acknowledging nursing's key role in the care of the growing population of older adults. This program has supported 249 nurse scientists with pre- and postdoctoral awards. As a result of the program's success, several Building Academic Geriatric Nursing Capacity Program awardees formed an alumni organization to continue to advance the quality care of older adults. This group of Building Academic Geriatric Nursing Capacity Program awardees joined others receiving support from the John A. Hartford Foundation nursing initiatives to grow a formal organization, the Hartford Gerontological Nursing Leaders (HGNL). The purpose of this article is to present the development, accomplishments, and challenges of the HGNL, informing other professional nursing organizations that are experiencing similar accomplishments and challenges. This article also demonstrates the power of a funding initiative to grow an organization dedicated to impact gerontological health and health care through research, practice, education, and policy. PMID- 26802589 TI - Clinical Nurse Leader Integration Into Practice: Developing Theory To Guide Best Practice. AB - Numerous policy bodies have identified the clinical nurse leader (CNL) as an innovative new role for meeting higher health care quality standards. Although there is growing evidence of improved care environment and patient safety and quality outcomes after redesigning care delivery microsystems to integrate CNL practice, significant variation in CNL implementation has been noted across reports, making it difficult to causally link CNL practice to reported outcomes. This variability reflects the overall absence in the literature of a well-defined CNL theoretical framework to help guide standardized application in practice. To address this knowledge gap, an interpretive synthesis with a grounded theory analysis of CNL narratives was conducted to develop a theoretical model for CNL practice. The model clarifies CNL practice domains and proposes mechanisms by which CNL-integrated care delivery microsystems improve health care quality. The model highlights the need for a systematic approach to CNL implementation including a well-thought out strategy for care delivery redesign; a consistent, competency-based CNL workflow; and sustained macro-to-micro system leadership support. CNL practice can be considered an effective approach to organizing nursing care that maximizes the scope of nursing to influence the ways care is delivered by all professions within a clinical microsystem. PMID- 26802590 TI - Enacting a Vision for a Master's Entry Clinical Nurse Leader Program: Rethinking Nursing Education. AB - The need to educate nurses at the graduate level and provide them with a different skill set that broadens their view of health and nursing is clearly articulated by the American Association of Colleges of Nursing. Consequently, the role of the clinical nurse leader (CNL) was born. Responding to the need for providing a highly educated and credentialed professional at the bedside, Rush University College of Nursing made the bold move to phase out baccalaureate education and enact a prelicensure, master's entry CNL program. Although there is a clear need for this type of graduate, there is little in the literature to provide guidance to institutions that wish to develop this type of program. This paper describes the factors that came into play in making that decision, the process of curriculum development and implementation, the challenges encountered in implementing this type of program, and the outcomes that the program has evidenced since its inception. PMID- 26802591 TI - Service-Learning in Undergraduate Nursing Education: Where is the Reflection? AB - Service-Learning is recognized as a valuable pedagogy that involves experiential learning, reflection, and reciprocal learning. Reflection is a critical component because it assists students to develop critical thinking and social awareness as they reflect upon their experiential learning with community partners. Although there is a proliferation of literature about service-learning, upon closer examination, it is apparent that some authors do not place emphasis on reflection when reporting on service-learning projects. This begs the question, "Where is the reflection?" The purpose of this article is to provide an overview and describe misrepresentations and exemplars of service-learning. After providing an overview of service-learning, examples of how service-learning is misrepresented in the literature are discussed. Exemplars of service-learning are also cited. Calling attention to how service-learning is reported in the literature will increase awareness about the need to critically evaluate articles for evidence of reflection. PMID- 26802592 TI - Modifiable Factors that Support Political Participation by Nurses. AB - Political participation is an opportunity for individuals to give their time and energy in such a way that it benefits others and advances relevant agendas. Political participation is a key issue for nurses because they are familiar with clinical issues that directly impact health care policies instituted at the local, state, and federal levels. Collectively, nurses also represent the largest number of health care providers in the United States and are among the most trusted health professionals. However, there are many obstacles that prevent nurses from taking a more active role in politics, creating a gap in how nurses pursue and respond to political participation, or civic engagement. The purpose of this exploratory review is to identify modifiable factors that support political participation among nurses. A review of the extant literature revealed three primary factors that promote civic engagement among nurses: (a) integration of political education in the nursing curriculum; (b) value of active psychological engagement, including a personal interest in political knowledge and information; and (c) value of collective influence such as membership in professional organizations. PMID- 26802594 TI - Phylogenetic relationships of species of the oesophageal parasitic nematode genera Cyclostrongylus and Spirostrongylus (Strongyloidea: Chabertiidae: Cloacininae) with their wallaby hosts (Marsupialia: Macropodidae). AB - A phylogeny for seven species of Cyclostrongylus and the monotypic genus Spirostrongylus (Nematoda: Chabertiidae), all highly host specific parasites of the oesophagi of wallabies (Marsupialia: Macropodidae), was constructed using sequence data for the first and second internal transcribed spacers (ITS-1 and ITS-2) of the nuclear ribosomal DNA. There was no evidence for co-speciation, or for the sympatric or synxenic speciation of Cyclostrongylus alatus and Cyclostrongylus perplexus, both of which are parasites of Macropus rufogriseus. Rather, host switching, correlating with geographical distributions, appeared to provide some explanation of the pattern of speciation observed. PMID- 26802593 TI - Preparing Nursing Students for Interprofessional Practice: The Interdisciplinary Curriculum for Oncology Palliative Care Education. AB - Interprofessional educational experiences for baccalaureate nursing students are essential to prepare them for interprofessional communication, collaboration, and team work. Nurse educators are ideally positioned to develop and lead such initiatives. The purpose of this article is to describe the development and implementation of an interprofessional education (IPE) project involving students in nursing, medicine, social work, and chaplaincy. The Interdisciplinary Curriculum for Oncology Palliative Care Education project uses team-based palliative oncology education as the framework for teaching students interprofessional practice skills. The need for IPE is apparent, but there are very few comprehensive, successful projects for nurse educators to use as models. This article describes the development of the curriculum by the interprofessional faculty team. Issues encountered by nursing faculty members as they implemented the IPE experience are discussed. Solutions developed to address the issues and ongoing challenges are presented. This project can serve as a model of a successful IPE initiative involving nursing students. PMID- 26802595 TI - Lack of association between polymorphisms in the SIRT6 gene and longevity in a Chinese population. AB - Sirtuin 6 (SIRT6) has recently been demonstrated to play an important role in the regulation of longevity in mammals. We therefore aimed to determine whether common variations in the SIRT6 gene are associated with human longevity. Five tag single nucleotide polymorphisms (SNPs) across the SIRT6 gene and its 5 kb up /downstream region, including rs350852, rs350844, rs352493, rs4807546 and rs3760905, have been successfully determined in 616 unrelated Chinese long-lived individuals (LLIs) (mean age: 102.4 +/- 2.3 years) and 846 younger controls (mean age: 48.9 +/- 10.6 years) from Hainan Island, China. The allele and genotype frequencies of the five SNPs showed no statistically significant difference between the LLIs and controls (all P > 0.05). The five SNPs were in strong linkage disequilibrium and defined seven common haplotypes. Likewise, no association between these haplotypes and longevity was observed (all P > 0.05). The present study reveals that common genetic variations in the SIRT6 gene are not associated with human longevity. PMID- 26802596 TI - Sparse wavefield reconstruction and source detection using Compressed Sensing. AB - The paper presents a Compressed Sensing technique for the reconstruction of guided wavefields. Structural inspections based on the analysis of guided wavefields have proven to be effective at detecting and characterizing damage. However, wavefield detection is often a time consuming process, which limits practicality. The proposed reconstruction technique estimates the location of sources and structural features interacting with the waves from a set of sparse measurements. Such features include damage, described as a scattering source. The wavefield is reconstructed by employing information on the dispersion properties of the medium under consideration. The procedure is illustrated through a one dimensional analytical example, and subsequently applied to the reconstruction of an experimental wavefield in a composite panel with an artificial delamination. The results confirm the ability of the technique to identify the defect, while reconstructing the wavefield with good accuracy using a significantly reduced number of measurements. PMID- 26802597 TI - A low TSH profile predicts olanzapine-induced weight gain and relief by adjunctive topiramate in healthy male volunteers. AB - Second generation antipsychotics, like olanzapine (OLZ), have become the first line drug treatment for patients with schizophrenia. However, OLZ treatment is often associated with body weight (BW) gain and metabolic derangements. Therefore, the search for prospective markers for OLZ's negative side effects as well as adjunctive treatments to inhibit these has been of major interest. The aim of this study was to investigate in healthy male volunteers (age: 36 +/- 11 years; BW: 84 +/- 12 kg; BMI=25.5 +/- 2.5) whether adjunctive topiramate (TPM) administration opposes OLZ-induced weight gain over the course of 14 days treatment. In addition, we investigated behavioral, endocrine and metabolic characteristics as underlying and potentially predictive factors for weight regulation and/or metabolic derangements associated with OLZ and TPM treatment. While adjunctive TPM indeed reduced OLZ-induced weight gain (P<0.05, Mann-Whitney U), behavioral/metabolic/endocrine characteristics of OLZ treatment were not affected by TPM. Using multiple regression analysis, BW gain was the key factor explaining metabolic disturbances (e.g., plasma insulin- LDL interaction: P<0.01, R(2)=.320), and cumulative food intake during treatment was the best denominator of BW gain (P<0.01, R(2)=.534). Neither TPM treatment, nor its circulating levels, contributed to variation observed in DeltaBW. In a second multiple regression analysis, we observed that a low baseline thyrotropin profile (TSHAUC) before the start of drug treatment was associated with an increase in DeltaBW over the course of drug treatment (P<0.05, R(2)=.195). Adding TSHAUC as covariate revealed that adjunctive TPM treatment did attenuate OLZ induced BW gain (P<0.05, ANCOVA). Further exploration of the circulating thyroid hormones revealed that individuals with a low plasma TSH profile were also those that were most sensitive to adjunctive TPM treatment blocking OLZ-induced DeltaBW gain. Others have shown that OLZ-induced BW gain is associated with improvement in brief psychiatric rating scores (BPRS); adjunctive TPM treatment may be a solution specifically for those subjects susceptible to OLZ-induced rapid weight gain who on a therapeutic level-benefit most of OLZ treatment. PMID- 26802598 TI - Hormone levels in neonatal hair reflect prior maternal stress exposure during pregnancy. AB - Hormones present in hair provide summative information about endocrine activity while the hair was growing. Therefore, it can be collected from an infant after birth and still provide retrospective information about hormone exposure during prenatal development. We employed this approach to determine whether a delimited period of maternal stress during pregnancy affected the concentrations of glucocorticoids and gonadal hormones in the hair of neonatal rhesus monkeys. Hair from 22 infant monkeys exposed to 5 weeks of gestational disturbance was compared to specimens from 13 infants from undisturbed control pregnancies. Using an LC/MS/MS based technique, which permitted seven steroid hormones to be quantified simultaneously, we found 2 hormones were significantly different in infants from disturbed pregnancies. Cortisol and testosterone levels were lower in the hair of both male and female neonates. Maternal hair hormone levels collected on the same day after delivery no longer showed effects of the disturbance earlier during pregnancy. This study documents that a period of acute stress, lasting for 20% of gestation, has sustained effects on the hormones to which a developing fetus is exposed. PMID- 26802600 TI - Physician Preparation for the American Board of Emergency Medicine ConCert Examination. AB - OBJECTIVES: To maintain certification by the American Board of Emergency Medicine (ABEM), physicians are required to pass the Continuous Certification (ConCert) examination at least every 10 years. On the 2014 ConCert postexamination survey, ABEM sought to understand the manner in which ABEM diplomates prepared for the test and to identify associations between test preparation approaches and performance on the ConCert examination. METHODS: This was a cross-sectional survey study. The survey was administered at the end of the 2014 ConCert examination. Analyses included chi-square and linear regression to determine the association of preparation methods with performance. RESULTS: Of the 2,431 on time test-takers, 2,338 (96.2%) were included. The most commonly used study approach was the review of written materials designed for test preparation (1,585; 67.8%), followed by an online training course (1,006; 43.0%). There were 758 (32.4%) physicians who took a single onsite board review course, while 41 (1.8%) took two or more onsite courses. Most physicians (1,611; 68.9%) spent over 35 hours preparing for the ConCert examination. The study method that was most associated with favorable test scores was the review of written materials designed for test preparation (p < 0.001). Attending an onsite preparation course was associated with poorer performance (p < 0.001). There was a significant association between no additional preparation and failing the examination (chi square with Yates correction; p = 0.001). CONCLUSIONS: A substantial majority (97.8%) of physicians taking the 2014 ABEM ConCert examination prepared for it. The majority of physicians used written materials specifically designed for test preparation. Reviewing written materials designed for test preparation was associated with the highest performance. PMID- 26802599 TI - Hypothalamic-pituitary-adrenal axis activity under resting conditions and cardiovascular risk factors in adolescents. AB - BACKGROUND: Activation of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with higher levels of cardiovascular (CVD) risk factors in adults. This study aimed to assess the relation between measures of HPA axis activity under resting conditions and CVD risk factors in a general population of adolescents at 17 years. METHODS: A total of 1134 adolescents from the Western Australian Pregnancy Cohort (Raine) Study had phenotypic and socio-demographic data. The associations between HPA axis measures (plasma ACTH, total cortisol, calculated free cortisol, corticosteroid binding globulin (CBG), and salivary cortisol) and a range of cardiovascular risk factors were examined using multivariable linear regression models, with adjustment for gender, adiposity, birth weight, gestational age, and socio-behavioural factors. RESULTS: Plasma total cortisol was positively associated with systolic blood pressure (SBP) (p=0.011), total cholesterol, HDL-cholesterol, and triglycerides (all p<0.001), and hs-CRP (p=0.047). Salivary cortisol was associated positively with HDL-C (p=0.033) and negatively with LDL-cholesterol (p=0.016); plasma calculated free cortisol was positively associated with triglycerides (p=0.006); plasma CBG was positively associated with total cholesterol and HDL-cholesterol (both p<0.001), LDL-cholesterol (p=0.022), and hs-CRP (p=0.001). After correction for multiple comparisons, significant associations remained for total cortisol with total cholesterol, HDL-C, and triglycerides; for calculated free cortisol with triglycerides; and for CBG with HDL-C, total cholesterol, and hs-CRP. Plasma ACTH was not associated with any cardiovascular risk factor. There was no association between BMI and any measure of HPA axis activity. CONCLUSION: In an adolescent population, HPA axis measures under resting conditions are associated with a range of CVD risk factors. Clarification of the mechanisms underlying these associations in adolescence would be an important step in understanding the evolution of adult CVD. PMID- 26802601 TI - CCL2 gene polymorphism is associated with post-transplant diabetes mellitus. AB - Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation, especially in recipients treated with calcineurin inhibitors. Previous studies suggest that chronic inflammation and chemokines play an important role in the pathogenesis of diabetes. Single-nucleotide polymorphisms (SNPs) can increase or decrease transcriptional activity and can change the production of chemokines. The aim of this study was to examine the association between CCL2 and CCL5 gene polymorphisms and the development of post transplant diabetes mellitus. The study included 315 patients who received kidney transplants and were treated with calcineurin inhibitors. Patients were divided into two subgroups: with PTDM (n=43) and without PTDM (n=272). An additive model of univariate Cox regression analysis showed that the hazard of PTDM development was significantly positively associated with the number of CCL2 rs1024611 G alleles (HR 1.65; 95%CI 1.08-2.53; p=0.021). Multivariate Cox regression analysis, taking into the account the recipient's sex, age and BMI, as well as the number of G alleles of the CCL2 rs1024611 polymorphism, revealed that this polymorphism is an independent risk factor for post-transplant diabetes. The results of our study suggest an association between the CCL2 gene rs1024611 G allele and PTDM in patients treated with tacrolimus or cyclosporine. PMID- 26802602 TI - Consistency and pathophysiological characterization of a rat polymicrobial sepsis model via the improved cecal ligation and puncture surgery. AB - Sepsis is the leading cause of death for critical ill patients and an essential focus in immunopharmacological research. The cecal ligation and puncture (CLP) model is regarded as a golden standard model for sepsis study. However, this animal model is easily affected by variability problems and dramatically affects pharmacological evaluation of anti-sepsis therapies, which requires standardized procedures and stable outcomes. Herein, the traditional syringe needle based puncture method was used as the major unstable factor for CLP models. Syringe needles created varied mortality in parallel experimental groups of CLP rats; they were inconsistent for severity control as mortality in CLP rats was not correlated with change in punctures, ligation lengths, or needle sizes. Moreover, the use of drainage tubes or strips, which was supposed to strengthen drainage stability, also failed to improve consistency of traditional syringe needles. To solve the consistency problem, an improved design of CLP surgery by puncture with newly-developed three-edged needles was described herein. In contrast to traditional syringe needles, these three-edged needles ensured more stable outcomes in repetitive groups. Furthermore, increased severity was found to be consistent with the enlarged needle size, as shown by the elevated mortality, increased proinflammatory cytokines, abnormal coagulation, worsen acidosis and more severe acute lung injury. In conclusion, application of the newly-developed three-edged needles provides a simple and feasible method to improve stability when conducting CLP surgery, which is significant for pharmacological studies on sepsis. PMID- 26802603 TI - Smad2 increases the apoptosis of activated human hepatic stellate cells induced by TRAIL. AB - The activation of hepatic stellate cells (HSCs) plays a critical role in the development of liver fibrosis. The induction of apoptosis in activated HSCs during the recovery phase of hepatic fibrosis represents a potential anti fibrotic therapy. We have previously shown that Smad2 protects against hepatic fibrogenesis; however, the role of Smad2 in the regulation of activated HSC apoptosis remains unknown. We hypothesized that Smad2 regulates the apoptosis of activated HSCs, leading to the resolution of liver fibrosis. To test this hypothesis, the livers of rats were harvested at 0 and 4 weeks after hepatic fibrosis was established by CCl4 injection. Furthermore, TGF-beta1-activated HSCs were treated with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) following the silencing or overexpression of Smad2. Both the phosphorylation of Smad2 and TRAIL were detected in fibrotic liver tissues. The results of TUNEL and alpha-SMA double-staining showed an increase in the apoptosis of activated HSCs during the spontaneous recovery phase. The knockdown of Smad2 reduced TRAIL induced apoptosis in TGF-beta1-activated human LX-2 cells and resulted in an increased expression of alpha-SMA and collagen I (Col. I). In contrast, the overexpression of Smad2 increased TRAIL-induced HSC apoptosis and reduced the expression of alpha-SMA and Col. I. The mechanisms underlying these findings were associated with the Smad2-mediated down-regulation of X-linked inhibitor of apoptosis protein (XIAP), resulting in enhanced caspase-3 activity and apoptosis. In conclusion, Smad2 enhances TRAIL-induced apoptosis in activated HSCs, which facilitates the resolution of hepatic fibrosis. PMID- 26802604 TI - Benefits of using heterologous polyclonal antibodies and potential applications to new and undertreated infectious pathogens. AB - BACKGROUND: Passive immunotherapy using polyclonal antibodies (immunoglobulins) has been used for over a century in the treatment and post-exposure prophylaxis of various infections and toxins. Heterologous polyclonal antibodies are obtained from animals hyperimmunised with a pathogen or toxin. AIMS: The aims of this review are to examine the history of animal polyclonal antibody therapy use, their development into safe and effective products and the potential application to humans for emerging and neglected infectious diseases. METHODS: A literature search of OVID Medline and OVID Embase databases was undertaken to identify articles on the safety, efficacy and ongoing development of polyclonal antibodies. The search contained database-specific MeSH and EMTREE terms in combination with pertinent text-words: polyclonal antibodies and rare/neglected diseases, antivenins, immunoglobulins, serum sickness, anaphylaxis, drug safety, post marketing surveillance, rabies, human influenza, Dengue, West Nile, Nipah, Hendra, Marburg, MERS, Hemorrhagic Fever Virus, and Crimean-Congo. No language limits were applied. The final search was completed on 20.06.2015. Of 1960 articles, title searches excluded many irrelevant articles, yielding 303 articles read in full. Of these, 179 are referenced in this study. RESULTS: Serum therapy was first used in the 1890s against diphtheria. Early preparation techniques yielded products contaminated with reactogenic animal proteins. The introduction of enzymatic digestion, and purification techniques substantially improved their safety profile. The removal of the Fc fragment of antibodies further reduces hypersensitivity reactions. Clinical studies have demonstrated the efficacy of polyclonal antibodies against various infections, toxins and venoms. Products are being developed against infections for which prophylactic and therapeutic options are currently limited, such as avian influenza, Ebola and other zoonotic viruses. CONCLUSIONS: Polyclonal antibodies have been successfully applied to rabies, envenomation and intoxication. Polyclonal production provides an exciting opportunity to revolutionise the prognosis of both longstanding neglected tropical diseases as well as emerging infectious threats to humans. PMID- 26802605 TI - The effect of mucoadhesive excipient on the nasal retention time of and the antibody responses induced by an intranasal influenza vaccine. AB - INTRODUCTION: Recently, we reported that intranasal vaccination of humans with whole inactivated influenza vaccine in the absence of mucosal adjuvant induced neutralizing antibody responses in the serum and nasal mucus. The mucoadhesive excipient carboxy-vinyl polymer (CVP) increases the viscosity and therefore mucoadhesiveness of intranasal medicaments and is an authorized excipient in Japan. In the present study, we analyzed the effect of adding CVP on intranasal whole inactivated influenza vaccine antigen dynamics and antibody responses. METHODS: Mice and nonhuman primates (NHPs) were intranasally administered the [(18)F]-radiolabeled vaccine and subjected to positron emission tomography analysis for 6h. Dendritic cells were stimulated in vitro with the vaccine mixed with or without a mucosal adjuvant (Ampligen) and/or CVP, after which the tumor necrosis factor (TNF)-alpha and interferon (IFN)-beta levels in the supernatants were measured. Cynomolgus monkeys were immunized intranasally with the vaccine mixed with Ampligen and/or CVP and their vaccine-specific serum IgG and IgA titers were measured on days 0 and 33. RESULTS: The vaccine was retained significantly longer in the nasal cavity of both mice and NHPs when it was delivered with CVP rather than PBS. Accumulation of the radiolabeled vaccine in the central nervous system was not detected in either model regardless of whether CVP was used. CVP only very weakly increased the TNF-alpha production of vaccine stimulated dendritic cells. IFN-beta production was not observed regardless of the presence or absence of CVP. CVP increased the vaccine-specific IgA antibody responses of the intranasally vaccinated cynomolgus macaques. CONCLUSION: CVP increased intranasal retention of whole inactivated influenza vaccine, did not promote antigen redirection to the central nervous system, and improved mucosal antibody responses. The mechanism probably relates to its mucoadhesive properties rather than its ability to directly stimulate the immune system. Intranasal vaccines with CVP may be a promising candidate vaccine formulation for humans. PMID- 26802607 TI - A new benzophenanthridine alkaloid and other bioactive constituents from the stem bark of Zanthoxylum heitzii. AB - Heitziquinone (7), a new benzophenanthridine alkaloid, together with five known compounds; isoarnottianamide (5), rhoifoline B (6), isobauerenol (8), 6 hydroxypellitorine (9) and sylvamide (10), were isolated as minor compounds from the hexane extract of stem bark from Zanthoxylum heitzii. Four previously reported compounds (1-4) were found, as well. Compounds 5 and 7 were both found to exist as 4:1 mixtures of two atropisomers. The structures were elucidated by 1D and 2D NMR spectroscopy and by mass spectrometry. Compounds 5-10 were identified for the first time in this species, and they are all rare natural compounds. Pellitorine (4), one of the main compounds from the hexane bark extract, was found to be responsible for the brine shrimp larvae toxicity (LC50 37 MUM, 8 MUg/ml) of the crude extract (LC50 24 MUg/ml). Low cytotoxicity against a macrophage cell line was observed. PMID- 26802606 TI - An initial examination of the potential role of T-cell immunity in protection against feline immunodeficiency virus (FIV) infection. AB - The importance of vaccine-induced T-cell immunity in conferring protection with prototype and commercial FIV vaccines is still unclear. Current studies performed adoptive transfer of T cells from prototype FIV-vaccinated cats to partial-to complete feline leukocyte antigen (FLA)-matched cats a day before either homologous FIVPet or heterologous-subtype pathogenic FIVFC1 challenge. Adoptive transfer (A-T) conferred a protection rate of 87% (13 of 15, p < 0.001) against FIVPet using the FLA-matched T cells, whereas all 12 control cats were unprotected. Furthermore, A-T conferred protection rate of 50% (6 of 12, p<0.023) against FIVFC1 using FLA-matched T cells, whereas all 8 control cats were unprotected. Transfer of FLA-matched T and B cells demonstrated that T cells are needed to confer A-T protection. In addition, complete FLA-matching and addition of T-cell numbers > 13 * 10(6) cells were required for A-T protection against FIVFC1 strain, reported to be a highly pathogenic virus resistant to vaccine induced neutralizing-antibodies. The addition of FLA-matched B cells alone was not protective. The poor quality of the anti-FIV T-cell immunity induced by the vaccine likely contributed to the lack of protection in an FLA-matched recipient against FIVFC1. The quality of the immune response was determined by the presence of high mRNA levels of cytolysin (perforin) and cytotoxins (granzymes A, B, and H) and T helper-1 cytokines (interferon-gamma [IFNgamma] and IL2). Increased cytokine, cytolysin and cytotoxin production was detected in the donors which conferred protection in A-T studies. In addition, the CD4(+) and CD8(+) T-cell proliferation and/or IFNgamma responses to FIV p24 and reverse transcriptase increased with each year in cats receiving 1X-3X vaccine boosts over 4 years. These studies demonstrate that anti-FIV T-cell immunity induced by vaccination with a dual-subtype FIV vaccine is essential for prophylactic protection against AIDS lentiviruses such as FIV and potentially HIV-1. PMID- 26802609 TI - A Rare Complication After Endovascular Aneurysm Repair: Disconnection of the Suprarenal Stent of a Zenith Endograft. AB - PURPOSE: To report a disconnection between the bare suprarenal stent and the main body of a Zenith endograft. CASE REPORT: A 79-year-old man with a history of successful endovascular repair of an aortic aneurysm presented a sudden episode of hypotension and hematuria. He had undergone implantation of a Zenith bifurcated device 8 years earlier in 2006. Plain abdominal radiography and computed tomography showed disconnection of the uncovered proximal stent, which led to endograft migration and type Ia endoleak. The patient also presented with distal endoleaks at the attachment sites in both common iliac arteries. The aneurysm sac diameter had increased from 52 to 96 mm. A proximal aortic cuff and bilateral iliac extensions were deployed via a common femoral artery access. Completion angiography did not show endoleak. CONCLUSION: After publication of a few such cases with the older Zenith device, the union between the suprarenal stent and main body was reinforced in 2002 to prevent this complication. Since modification of the device, this sequela had not been described. The reappearance of this complication underscores the need for continued surveillance, considering that these late events may require a reintervention to maintain the clinical success of the procedure. PMID- 26802608 TI - Ericoside, a new antibacterial biflavonoid from Erica mannii (Ericaceae). AB - A new dihydroflavonol-flavonol biflavonoid derivative, named ericoside was isolated from the ethanol extract of the whole plant of Erica mannii along with the known flavonoid, taxifolin 3-O-alpha-L-rhamnopyranoside; and two readily available sterols (sitosterol, sitosterol 3-O-beta-D-glucopyranoside). The isolation was performed using chromatographic methods and the structure of purified molecules were elucidated using spectroscopic techniques (e.g. MS, NMR) and by comparison with literature data. The crude ethanol extract, ericoside, and taxifolin 3-O-alpha-L-rhamnopyranoside were tested against ten Gram-negative bacteria including multidrug resistant clinical isolates using a broth microdilution method. The crude ethanol extract showed no noteworthy activity. Of the purified compounds, ericoside displayed moderate activity against the resistant Escherichia coli AG100 with a MIC of 64 MUg/mL. PMID- 26802610 TI - Endovascular Treatment of Degenerative Aneurysms Involving Only the Descending Thoracic Aorta: Systematic Review and Meta-analysis. AB - PURPOSE: To determine the efficacy of thoracic endovascular aortic repair (TEVAR) for degenerative aneurysm involving only the descending thoracic aorta (DTAA). METHODS: An English-language literature review was performed through PubMed, Scopus, and Google Scholar to identify any study evaluating the outcomes of TEVAR for DTAA. The main endpoints of this analysis were all-cause 30-day and late postoperative mortality. Secondary outcome measures were procedure success, vascular access complications, paraplegia, stroke, early endoleaks during the index hospitalization, aneurysm-related death, reinterventions, and conversion to open repair. To control for the anticipated heterogeneity among small observational studies, absolute values and means were pooled using random effects models; the results are expressed as pooled proportions, means, or risk ratio (RR) with 95% confidence intervals (CIs). RESULTS: Eleven studies reporting on 673 patients (mean age 72.6 years, mean aneurysm diameter 62.9 cm) with DTAA were selected for the analysis. Technical success was reported in 91.0% of patients, and vascular access complications requiring repair were encountered in 9.7% of cases. Pooled overall 30-day, 1-year, 2-year, and 3-year survival rates were 96.0%, 80.3%, 77.3%, and 74.0%, respectively. Five studies compared the results of TEVAR after elective (n=151) and urgent/emergent procedure (n=77); the latter was a predictor of 30-day mortality (17.1% vs 1.8%, RR 3.83, 95% CI 1.18 to 12.40, p=0.025). Paraplegia occurred in 3.2% of patients and was permanent in 1.4% of patients. The stroke rate was 2.7%. Early type I endoleak was observed in 7.3%, type II endoleak in 2.0%, and type III in 1.2% of patients. The mean follow up of 9 studies was 22.3 months. At 3 years, freedom from reintervention was 90.3%. Death secondary to aneurysm rupture and/or fistula was reported in 3.2% of patients. CONCLUSION: Current results indicate that TEVAR for DTAA can be performed with rather high technical success, low postoperative morbidity, and good 3-year survival. PMID- 26802611 TI - Initial Experience in the Treatment of Extensive Iliac Artery Aneurysms With the Nellix Aneurysm Sealing System. AB - PURPOSE: To assess the feasibility and effectiveness of the Nellix prosthesis in the treatment of common iliac artery aneurysms. METHODS: Between May 2013 and June 2015, 230 patients underwent implantation of the Nellix device at 2 institutions. Fifty of these patients (mean age 76 years; 35 men) were identified as having 60 common iliac artery aneurysms (CIAAs) with a median diameter of 4 cm (range 3.5-7). The majority of patients had aortoiliac aneurysms (5, 70%), 10 (20%) had isolated CIAAs, and 5 (10%) had iliac anastomotic aneurysms after aortoiliac bypass. In 20 patients, the iliac aneurysm was the indication for the intervention; in the other 30 patients, the endovascular iliac repair was an adjunct procedure to endovascular aneurysm sealing (EVAS). An iliac branch device (IBD) was used when feasible to preserve flow to the internal iliac artery. RESULTS: Seventeen (34%) patients underwent elective implantation of the Nellix graft in combination with an IBD, 33 (66%) patients underwent Nellix sealing of the CIAA using 1 (n=5), 2 (n=22), or 3 Nellix grafts (2 bilateral grafts and 1 graft as an extension to the external iliac artery in 6 patients). The technical success rate was 100%, and no graft-related complications were reported postoperatively. No buttock claudication, reinterventions, graft thrombosis, or endoleaks were observed during a mean follow-up of 12 months. CONCLUSION: Our initial experience demonstrates that Nellix grafts are feasible and safe for the treatment of extensive iliac artery aneurysms. The long-term durability of these grafts should be validated in larger patient cohorts before this promising alternative endovascular technique can gain widespread acceptance. PMID- 26802612 TI - Outcomes of 1000 Carotid Wallstent Implantations: Single-Center Experience. AB - PURPOSE: To evaluate the outcomes of carotid artery stenting (CAS) with Wallstents in a single-center experience. METHODS: From January 2003 to December 2013, 1000 carotid artery lesions were treated with Carotid Wallstents under cerebral protection in 877 patients (mean age 71.7 +/- 8 years; 621 men). Indications for treatment were de novo lesions (>70% asymptomatic and >60% symptomatic); stenoses following carotid endarterectomy, radiation, or neck surgery; contralateral laryngeal nerve palsy; and high surgical risk. All the patients underwent duplex ultrasound and clinical evaluation during follow-up; radiography was performed when fracture or stent migration was suggested by ultrasound. RESULTS: Procedure success was achieved in 99.3% of patients. Major and minor 30-day adverse events occurred in 2.1% of patients, including stroke (1.8%: 1.3% minor, 0.5% major), myocardial infarction (0.1%), and death (0.2%). Plaque morphology, nature of stenosis, and symptomatic status were significantly associated with the risk of postoperative neurologic events. Restenosis occurred in 3.2% at a mean 45.5-month follow-up and was significantly associated with diabetes, smoking, symptomatic stenosis, de novo stenosis, and calcification (plaque III/IV). No fracture or migration was registered during follow-up. CONCLUSION: CAS is a valid method for treating carotid artery disease, with very low rates of major adverse events and neurologic complications. The Carotid Wallstent seems to have excellent results, even with complex plaque morphology, and a low incidence of restenosis at follow-up. PMID- 26802613 TI - Assessment of tenderness of aged bovine gluteus medius muscles using Raman spectroscopy. AB - A portable 671 nm Raman system was evaluated as a rapid and non-destructive device for the assessment of beef tenderness using 175 gluteus medius muscles (99 for calibration, 76 for validation) aged at -1 degrees C and 7 degrees C for fourteen days. Raman and shear force (SF) measurements were performed with the aged beef. The samples stored at -1 degrees C showed on average only slightly increased SF values. The correlation of Raman spectra with SF using partial least squares regression yielded cross-validated predictions of SF for both storage temperatures with coefficients of determination R(2)cv=0.33-0.79. Validation with independent samples resulted in predictions with R(2)val=0.33. Using thresholds between 30 and 49N, tough and tender samples could be discriminated with partial least squares discriminant analysis with 70-88% and 59-80% accuracy during cross validation and validation, respectively. These results demonstrate the principle feasibility to predict the SF and thus toughness of raw, aged gluteus beef cuts with a portable Raman device showing potential for grading beef cuts. PMID- 26802614 TI - Disorder of endoplasmic reticulum calcium channel components is associated with the increased apoptotic potential in pale, soft, exudative pork. AB - Eight pale, soft and exudative (PSE) and eight reddish-pink, firm and non exudative (RFN) porcine longissimus muscle samples were selected based on pH and L* at 1h postmortem (PM), and drip loss at 24h PM, and used to evaluate the cellular calcium and apoptosis status. We found that SERCA1 was decreased, while IP3R was decreased in PSE meat (P<0.05), indicative of the overloaded sarcoplasmic calcium status. In PSE meat, the pro-apoptotic factor BAX was increased while the anti-apoptotic factor Bcl-2 was decreased (P<0.05). The significantly increased activity of caspase 3 and the expression of its cleavage fragment suggested higher apoptotic potential in PSE meat compared with RFN meat (P<0.05). Moreover, the significantly higher expression level of cytochrome C (P<0.05) suggests the important role of mitochondria during apoptosis appearance in PSE meat. Taken together, our data inferred that the calcium channel disorder present in PSE meat was associated with the increased apoptotic potential. PMID- 26802615 TI - Predicting discharge destination after stroke: A systematic review. AB - Different factors have been studied and proven to significantly influence discharge destination of acute stroke patients after hospitalization. Few reviews have been published combining the results of these studies. Therefore we aim to present an overview of the studies conducted regarding these predicting factors. Through conducting a systematic review we aimed to study the different predictive factors influencing discharge destination of acute stroke patients after hospitalization. Nineteen articles were selected in accordance with the research question and inclusion criteria. The factors found were, according to their significance in the articles, subcategorized in age, gender, functional status, cognitive status, race and ethnicity, co morbidities, education, stroke characteristics, social and living situation. The main factors significantly associated with other than home discharge were functional dependence/comorbidities, neurocognitive dysfunction and previous living circumstances/marital status. A medium or large infarct is associated with institutionalization. The stroke volume is not associated with home discharge. The effect of other factors remain controversial and results differ between studies. These include: age, gender, race, affected hemisphere and availability of a caregiver not living at home. Factors such as education, hospital complications, geographic location and FIM progression during hospitalization have not been studied sufficiently. PMID- 26802616 TI - Long-term quality of life after posterior cervical foraminotomy for radiculopathy. AB - OBJECTIVES: Cervical radiculopathy may cause symptoms and loss of function that can lead to a significant reduction in health related quality of life (HRQOL). As part of a comprehensive review of long-term outcomes, we examined HRQOL in a large cohort of patients undergoing posterior cervical foraminotomy (FOR) for radiculopathy. PATIENTS AND METHODS: 338 patients who underwent FOR between 1990 and 2009 participated in a telephone interview designed to measure symptomatic and functional improvements following surgery. We also administered the EQ-5D, a standardized tool for assessing HRQOL. We analyzed this data for associations between patient and treatment characteristics, improvements in symptoms and function, and HRQOL as measured by the EQ-5D. RESULTS: Mean follow-up was 10.0 years. The average EQ-5D at follow-up was 0.81+/-0.18, and improvements in pain, weakness and function as well as ability to return to work correlated with improved EQ-5D score (p<0.0001). There was no correlation between length of follow-up and EQ-5D score (p=0.980). Additionally, there was no difference between mean EQ-5D score for soft disc versus osteophyte pathology (0.84 versus 0.81, p=0.21). CONCLUSION: These data provide evidence that FOR for cervical radiculopathy is associated with improved HRQOL at long-term follow-up. The lack of correlation between length of follow-up and HRQOL suggests that FOR is a durable treatment option. Moreover, FOR is associated with improved HRQOL whether radiculopathy is due to soft disc or osteophyte pathology. PMID- 26802617 TI - Heterokaryon analysis of a Cdc48-like gene, CpCdc48, from the chestnut blight fungus Cryphonectria parasitica demonstrates it is essential for cell division and growth. AB - Functional analysis of a cell division cycle 48 (CDC48) ortholog, CpCdc48, from Cryphonectria parasitica was performed via construction of a CpCdc48-null mutant. Genotype analysis revealed that the putative CpCdc48-null mutant was a heterokaryotic transformant containing two different types of nuclei (i.e., one with the wild-type CpCdc48 allele and the other with the CpCdc48-null mutant allele). Although stable mycelial growth of the heterokaryotic transformant was observed on media containing hygromycin B, neither germination nor growth of the resulting spores was observed on selection media, suggesting that the CpCdc48 gene is essential. Microscopic analysis of germinated conidia from the heterokaryon demonstrated that although there were normal germinating spores due to the wild-type conidia, there were many residual conidia that did not germinate. However, with prolonged incubation, non-germinating conidia began to swell into gigantic globose spores. DAPI staining and FACS analysis of the gigantic spores revealed the presence of multiple nuclei. These gigantic conidia did not show any signs of polarized growth and underwent autolysis with further incubation. These findings indicate that the CpCdc48 gene is responsible for delayed cell cycle during spore germination, resulting in some karyokinesis, but not following spore cytokinesis. Thus, CpCdc48 is essential for cell division and polarized growth. PMID- 26802618 TI - Maternal residential proximity to major roadways at delivery and childhood central nervous system tumors. AB - BACKGROUND: Due to concerns over the impact of traffic-related air pollution on childhood cancers, we evaluated the association between residential proximity to major roadways and childhood central nervous system (CNS) tumors. METHODS: The Texas Cancer Registry provided information on children diagnosed with a CNS tumor at <5 years of age and born in Texas for the period 2003-2009 (n=315). Birth certificate controls were frequency matched to cases (5:1) on birth year (n=1575). We assigned exposures to traffic-related air pollution using residential proximity to major roadways based on the maternal residence at the time of delivery. Logistic regression was used to generate unadjusted and adjusted odds ratios and 95% confidence intervals (CI). We evaluated CNS tumors as a group and by histologic type. RESULTS: Maternal residential proximity to major roadways at delivery was positively associated with the odds of offspring having a CNS tumor. Specifically, for every kilometer closer to a major roadway, the odds of offspring having a CNS tumor increased by 30% (95% CI: 1.0, 1.7). Mothers living <=500 meters (m) from a major roadway were 31% (95% CI: 1.0, 1.8) more likely to have offspring with any CNS tumor and 3.1-times (95% CI: 0.9, 10.4) more likely to have offspring with an ependymoma compared to mothers living >500m from the nearest major roadway. Moreover, compared to mothers living in areas with low roadway density, those living in areas with high roadway density were 51% (95% CI: 1.1, 2.1) more likely to have offspring with any CNS tumor and 4.2-times (95% CI: 1.2, 14.9) more likely to have offspring with an ependymoma. There were no statistically significant associations observed between continuous distance to major roadways and ependymoma as well as between the proximity measures and the other evaluated CNS tumor phenotypic groups. CONCLUSIONS: The results of this large population-based study indicate that mothers who live near major roadways or in areas with high roadway density may be more likely to have offspring with a CNS tumor, particularly an ependymoma. PMID- 26802619 TI - Perfluorooctanoic acid exposure and natural menopause: A longitudinal study in a community cohort. AB - INTRODUCTION: Perfluorooctanoic acid (PFOA), a suspected endocrine disruptor, is a bio-persistent chemical found at low levels in the serum of nearly all U.S. residents. Early menopause has been positively associated with serum PFOA in prior cross-sectional studies. METHODS: We conducted a longitudinal analysis of age at menopause among women, aged >=40 years, (N=8759) in a Mid-Ohio Valley community cohort, exposed to high PFOA levels via contaminated drinking water. Using estimated retrospective year-specific serum PFOA concentrations (1951 2011), we examined the associations between PFOA, as cumulative exposure or year specific serum estimates, and natural menopause using a Cox proportional hazards models. As participants were initially recruited in 2005-2006, we also analyzed the cohort prospectively (i.e., from the time of enrollment), using both modeled cumulative PFOA, and PFOA serum levels measured in 2005-2006. Women with hysterectomy (a competing risk) were either censored or excluded from the analysis. RESULTS: Neither in the retrospective nor the prospective cohort did we find a significant (at alpha=0.05) trend between PFOA exposure and natural menopause. The non-significant, hazard ratios by quintile of increasing cumulative serum PFOA were 1.00 (referent), 1.00, 1.09, 1.05 and 1.06 (trend test for log cumulative exposure: p=0.37) with hysterectomies censored, and 1.00 (referent), 1.06, 1.13, 1.09 and 1.11 (trend test for log cumulative exposure: p=0.85) with hysterectomies excluded. Year-specific serum estimates were also not associated with early menopause. CONCLUSION: Our data suggest that earlier age at menopause is not associated with PFOA exposure. PMID- 26802620 TI - Brain infarction and blasts with bilobed nuclei in a patient with monocytic acute myeloid leukemia mimicking acute promyelocytic leukemia. AB - We are presenting a case of an adult male patient with monocytic acute myeloid leukemia (AML) who had on presentation brain infarction and bilobed nuclei had been demonstrated in many of the leukemic blasts. There was no laboratory evidence of acute disseminated intravascular coagulopathy, on presentation or later on. Initially the diagnosis of acute promyelocytic leukemia (APL) was considered, so all trans-retinoic acid (ATRA) was added to induction chemo therapy. As the diagnosis of APL was ruled out, based on the flow cytometry, fluorescent in situ hybridization and polymerase chain reaction findings, the ATRA was discontinued and the patient continued on the standard AML chemo therapy induction regimen. Later on chromosomal analysis was also normal. Sever dehydration on presentation, would have contributed to brain infarction. AML particularly monocytic, can mimic APL, especially its microgranular variant. The possible ATRA therapy side effects, can be avoided by early confirmation of the diagnosis. PMID- 26802621 TI - Solid-type primary intraosseous squamous-cell carcinoma in the mandible: Report of a rare case. AB - Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare malignant neoplasm that has an exquisitely exclusive affection to the jawbone. It is defined as squamous cell carcinoma arising within the jaw and developing from residual odontogenic epithelium or from a preexisting odontogenic cyst or tumor. The solid-type of this tumor is a central jaw carcinoma arising de novo and has no initial connection with the oral mucosa. Herein, we report a case of solid type PIOSCC involving the mandible in a 37-year-old male patient elucidating its histopathological and imaging findings. The patient underwent surgical resection followed by post-operative adjuvant radiotherapy. The close 2-year follow up of the patient revealed neither locoregional nor distant metastasis. PMID- 26802622 TI - Wilms tumor: Successes and challenges in management outside of cooperative clinical trials. AB - OBJECTIVE/BACKGROUND: Management of Wilms tumor (WT) in children depends on a multidisciplinary approach to treatment, and outcomes have significantly improved as reported by cooperative group clinical trials. Here, we review the clinical outcomes of patients with WT and identify challenges and barriers encountered in multidisciplinary management outside of cooperative clinical trials. METHODS: We retrospectively reviewed the clinical records of 35 children with WT treated between April 2002 and June 2013 at the Children's Cancer Institute in Lebanon. RESULTS: Upfront resection was performed in 23 cases. Biopsies were performed for Stage V tumors (n=4), those with unresectable tumors or inferior vena caval thrombus (n=5), and patients who had partial surgery performed elsewhere prior to presentation (n=2). One patient died due to toxicity prior to surgery. The tumor was Stage I in eight patients, Stage II in five patients, Stages III and IV in nine patients each, and bilateral (Stage V) in four patients. Adherence to The National Wilms Tumor Study-5 recommendations was adequate. At the time of analysis, 30 patients were free of disease and four patients had relapse-all having metastatic disease initially. CONCLUSION: The National Wilms Tumor Study-5 therapy resulted in favorable outcomes in children with nonmetastatic Wilms tumor in the setting of a multidisciplinary approach to therapy and resolution of financial barriers to medical care. Upstaging due to prior intervention and lung radiation therapy to all those with computed tomography-detected lung nodules may both have resulted in overtreatment of a subset of patients. Finally, the relatively high incidence of bilateral tumors suggests the need for further genetic and molecular studies in this patient population. PMID- 26802623 TI - Co-existence of AML1-ETO and BCR-ABL1 transcripts in a relapsed patient of acute myeloid leukemia with favorable risk group: A coincidence or clonal evolution? AB - Prognosis of acute myeloid leukemia relies heavily on the cytogenetic and molecular abnormalities. AML1-ETO fusion protein resulting from t(8;21), a recurring cytogenetic abnormality, is known to be associated with favorable prognosis. Additional molecular defects may, however, co-operate with the fusion proteins and alter the course of the disease. Among the additional cytogenetic defects, presence of Philadelphia (Ph) chromosome has rarely been documented in this subtype. Little is known about the consequences of its interactions with AML1-ETO, and its effect on morphological and clinical picture. Moreover, Ph+ clones or subclones may appear at any point during the disease course. We herein report one such unusual case of a 26-year-old female, who was diagnosed to have t(8;21) and managed accordingly. During disease relapse after 2.5years, the bone marrow showed extensive eosinophilia and basophilia. Subsequent molecular testing showed the presence of BCR-ABL in addition to the AML1-ETO fusion product. PMID- 26802624 TI - Venomous snakebites in children in southern Croatia. AB - This retrospective study represents observation of 160 children and adolescents aged up to 18 years that experienced venomous snakebites in southern Croatia and were treated in the Clinical Department of Infectious Diseases in the University Hospital Centre Split from 1979 to 2013. The main purpose of this research was to determine the epidemiological characteristics, clinical presentation, local and general complications, and received treatment. Most bites occurred during warm months, from early May to late August (80%), mostly in May and June. Upper limb bites were more frequent (59%) than lower limb bites (40%). Out of the total number of poisoned children, 24% developed local, and 25% general complications. The most common local complications were haemorrhagic blisters that occurred in 20% children, followed by compartment syndrome presented in 7.5% patients. The most dominated general complication was cranial nerve paresis or paralysis, which was identified in 11.2% patients, whereas shock symptoms were registrated in 7% children. According to severity of poisoning, 9.4% children had minor, 35% mild, 30.6% moderate, and 24.4% had severe clinical manifestation of envenomation. Only one (0.6%) child passed away because of snakebite directly on the neck. All patients received antivenom produced by the Institute of Immunology in Zagreb, tetanus prophylaxis as well, and almost all of them received antibiotics, and a great majority of them also received corticosteroids and antihistamines. Neighter anaphylactic reaction nor serum disease were noticed in our patients after administrating antivenom. A total of 26% children underwent surgical interventions, and incision of haemorrhagic blister was the most common applied surgical treatment, which was preformed in 15.6% patients, while fasciotomy was done in 7.5% subjects. All of our surgically treated patients recovered successfully. PMID- 26802625 TI - The Phoneutria nigriventer spider toxin, PnTx4-5-5, promotes neuronal survival by blocking NMDA receptors. AB - Spider toxins are recognized as useful sources of bioactive substances, showing a wide range of pharmacological effects on neurotransmission. Several spider toxins have been identified biochemically and some of them are specific glutamate receptors antagonists. Previous data indicate that PnTx4-5-5, a toxin isolated from the spider Phoneutria nigriventer, inhibits the N-methyl-d-aspartate receptor (NMDAR), with little or no effect on AMPA, kainate or GABA receptors. In agreement with these results, our findings in this study show that PnTx4-5-5 reduces the amplitude of NMDAR-mediated EPSCs in hippocampal slices. It is well established that glutamate-mediated excitotoxic neuronal cell death occurs mainly via NMDAR activation. Thus, we decided to investigate whether PnTx4-5-5 would protect against various cell death insults. For that, we used primary-cultured corticostriatal neurons from wild type (WT) mice, as well as from a mouse model of Huntington's disease, BACHD. Our results showed that PnTx4-5-5 promotes neuroprotection of WT and BACHD neurons under the insult of high levels of glutamate. Moreover, the toxin is also able to protect WT neurons against amyloid beta (Abeta) peptide toxicity. These results indicate that the toxin PnTx4-5-5 is a potential neuroprotective drug. PMID- 26802626 TI - Breathlessness During the Last Week of Life in Palliative Care: An Australian Prospective, Longitudinal Study. AB - CONTEXT: Breathlessness is a major cause of suffering and distress, and little is known about the trajectory of breathlessness near death. OBJECTIVES: To determine the trajectory and clinical-demographic factors associated with breathlessness in the last week of life in patients receiving specialist palliative care. METHODS: This was a prospective, longitudinal cohort study using national data on specialist palliative care from the Australian Palliative Care Outcomes Collaboration. We included patients in the Australian Palliative Care Outcomes Collaboration who died between July 1, 2013 and June 30, 2014 with at least one measurement of breathlessness on a 0-10 numerical rating scale in the week before death. The trajectory and factors associated with breathlessness were analyzed using multivariate random-effects linear regression. RESULTS: A total 12,778 patients from 87 services (33,404 data points) were analyzed. The average observed breathlessness was 2.1 points and remained constant over time. Thirty five percent reported moderate to severe distress (numerical rating scale >=4) at some time in their last week. Factors associated with higher breathlessness were younger age, male gender, cardiopulmonary involvement, concurrent fatigue, nausea, pain, sleeping problems, higher Australia-modified Karnofsky Performance Status, and clinical instability in the multivariate analysis. Respiratory failure showed the largest association (mean adjusted difference 3.1 points; 95% confidence interval, 2.8-3.4). CONCLUSION: Although breathlessness has been reported to worsen in the last months, the mean severity remained stable in the final week of life. In specialized palliative care, one in three people experienced significant breathlessness especially in respiratory disease. PMID- 26802627 TI - Trogocytosis-associated cell to cell spread of intracellular bacterial pathogens. AB - Macrophages are myeloid-derived phagocytic cells and one of the first immune cell types to respond to microbial infections. However, a number of bacterial pathogens are resistant to the antimicrobial activities of macrophages and can grow within these cells. Macrophages have other immune surveillance roles including the acquisition of cytosolic components from multiple types of cells. We hypothesized that intracellular pathogens that can replicate within macrophages could also exploit cytosolic transfer to facilitate bacterial spread. We found that viable Francisella tularensis, as well as Salmonella enterica bacteria transferred from infected cells to uninfected macrophages along with other cytosolic material through a transient, contact dependent mechanism. Bacterial transfer occurred when the host cells exchanged plasma membrane proteins and cytosol via a trogocytosis related process leaving both donor and recipient cells intact and viable. Trogocytosis was strongly associated with infection in mice, suggesting that direct bacterial transfer occurs by this process in vivo. PMID- 26802628 TI - Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function. AB - Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One of the proteases is the a disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase of the Alzheimer's disease amyloid precursor protein. ADAM10 is also required for neuronal network functions in murine brain, but neuronal ADAM10 substrates are only partly known. With a proteomic analysis of Adam10-deficient neurons we identified 91, mostly novel ADAM10 substrate candidates, making ADAM10 a major protease for membrane proteins in the nervous system. Several novel substrates, including the neuronal cell adhesion protein NrCAM, are involved in brain development. Indeed, we detected mistargeted axons in the olfactory bulb of conditional ADAM10-/- mice, which correlate with reduced cleavage of NrCAM, NCAM and other ADAM10 substrates. In summary, the novel ADAM10 substrates provide a molecular basis for neuronal network dysfunctions in conditional ADAM10-/- mice and demonstrate a fundamental function of ADAM10 in the brain. PMID- 26802629 TI - Unnatural amino acid photo-crosslinking of the IKs channel complex demonstrates a KCNE1:KCNQ1 stoichiometry of up to 4:4. AB - Cardiac repolarization is determined in part by the slow delayed rectifier current (IKs), through the tetrameric voltage-gated ion channel, KCNQ1, and its beta-subunit, KCNE1. The stoichiometry between alpha and beta-subunits has been controversial with studies reporting either a strict 2 KCNE1:4 KCNQ1 or a variable ratio up to 4:4. We used IKs fusion proteins linking KCNE1 to one (EQ), two (EQQ) or four (EQQQQ) KCNQ1 subunits, to reproduce compulsory 4:4, 2:4 or 1:4 stoichiometries. Whole cell and single-channel recordings showed EQQ and EQQQQ to have increasingly hyperpolarized activation, reduced conductance, and shorter first latency of opening compared to EQ - all abolished by the addition of KCNE1. As well, using a UV-crosslinking unnatural amino acid in KCNE1, we found EQQQQ and EQQ crosslinking rates to be progressively slowed compared to KCNQ1, which demonstrates that no intrinsic mechanism limits the association of up to four beta-subunits within the IKs complex. PMID- 26802630 TI - Development of a method for estimating total CH4 emission from rice paddies in Japan using the DNDC-Rice model. AB - Methane (CH4) is a greenhouse gas, and paddy fields are one of its main anthropogenic emission sources. To mitigate this emission based on effective management measures, CH4 emission from paddy fields must be quantified at a national scale. In Japan, country-specific emission factors have been applied since 2003 to estimate national CH4 emission from paddy fields. However, this method cannot account for the effects of weather conditions and temporal variability of nitrogen fertilizer and organic matter application rates; thus, the estimated emission is highly uncertain. To improve the accuracy of national scale estimates, we calculated country-specific emission factors using the DeNitrification-DeComposition-Rice (DNDC-Rice) model. First, we calculated CH4 emission from 1981 to 2010 using 986 datasets that included soil properties, meteorological data, and field management data. Using the simulated site-specific emission, we calculated annual mean emission for each of Japan's seven administrative regions, two water management regimes (continuous flooding and conventional mid-season drainage), and three soil drainage rates (slow, moderate, and fast). The mean emission was positively correlated with organic carbon input to the field, and we developed linear regressions for the relationships among the regions, water management regimes, and drainage rates. The regression results were within the range of published observation values for site-specific relationships between CH4 emission and organic carbon input rates. This suggests that the regressions provide a simplified method for estimating CH4 emission from Japanese paddy fields, though some modifications can further improve the estimation accuracy. PMID- 26802631 TI - The written expression abilities of adolescents with Attention Deficit/Hyperactivity Disorder. AB - Students with Attention-Deficit/Hyperactivity Disorder (ADHD) often experience deficits in academic achievement. Written expression abilities in this population have not been extensively studied but existing prevalence estimates suggest that rates of comorbid writing underachievement may be substantially higher than rates of comorbid reading and mathematics underachievement. The current study examined written expression abilities in a school-based sample of 326 middle school age students with ADHD. The prevalence of written expression impairment, the associations between written expression and academic outcomes, and specific patterns of written expression were investigated. Students with ADHD in this sample experienced written expression impairment (17.2-22.4%) at a similar rate to reading impairment (17.0-24.3%) and at a slightly lower rate than mathematics impairment (24.7-36.3%). Students' written expression abilities were significantly associated with school grades and parent ratings of academic functioning, above and beyond the influence of intelligence. Analyses of patterns suggest that students with ADHD exhibit greater deficits in written expression tasks requiring organization and attention to detail, especially in the context of a complex task. PMID- 26802632 TI - Direct and dissolved oxygen involved photodegradation of MeO-PBDEs in water. AB - Photodegradation has been proved to be a crucial way of elimination for polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDEs (HO-PBDEs). However, it is still unknown whether methoxylated PBDEs (MeO-PBDEs) can also undergo photodegradation. In this study, 4'-MeO-BDE-17, 5-MeO-BDE-47, 5'-MeO-BDE 99, 6-MeO-BDE-47 and 6-MeO-BDE-85 were selected as targets to investigate their photodegradation in water. Meanwhile, the effects of dissolved oxygen on the photoreactions of MeO-PBDEs were also unveiled. Simulated sunlight experiments indicate that 6-MeO-BDE-47 resisted photodegradation for 20h, while other MeO PBDEs underwent relatively fast photodegradation, which was greatly susceptible to the substitution patterns of methoxyl and bromine. Photo-excited MeO-PBDEs (except 6-MeO-BDE-47) can sensitize dissolved oxygen to generate singlet oxygen ((1)O2) and superoxide anion radical (O2(-)). The generated (1)O2 cannot degrade the MeO-PBDEs, whereas O2(-) was reactive with MeO-PBDEs. The contribution of dissolved oxygen to the photodegradation of 4'-MeO-BDE-17 and 6-MeO-BDE-85 was negligible; while the negative contribution was observed for 5-MeO-BDE-47 and 5' MeO-BDE-99. Hydrodebromination was a crucial photodegradation pathway for MeO PBDEs (excluding 4'-MeO-BDE-17 and 6-MeO-BDE-47). Eventually, direct photolysis half-lives of MeO-PBDEs except 6-MeO-BDE-47 in the surface waters at 40 N latitude were calculated to be 1.35-3.46d in midsummer and 6.39-17.47d in midwinter. PMID- 26802633 TI - What Do You Do with Your Dog Days of Summer? PMID- 26802634 TI - Letter to the Editor. PMID- 26802635 TI - To Bathe or Not to Bathe: The Neonatal Question. AB - After delivery, newborns go through a series of physiologic changes in an effort to adapt to extrauterine life, with preterm newborns more likely to experience medical problems following this transition. Neonatal hypothermia, defined as a temperature <36.5 degrees C, is a major contributor to neonatal mortality and morbidity. Early bathing may be a contributing factor to hypothermia and interfere with the premature neonate's ability to safely adapt to an extrauterine environment. Skin physiology, the physiologic changes that result from bathing, the importance of maintaining vernix for temperature stability, and how policy change and education-based programs for developmentally supportive care will be discussed in an attempt to improve patient care outcomes for neonates in the NICU. PMID- 26802636 TI - Adrenal Hemorrhage in Neonates: Unusual Presentation. AB - Adrenal hemorrhage (AH) is a relatively uncommon condition in newborns. It may be asymptomatic or may present with flank abdominal mass, anemia, jaundice, or rarely as scrotal bruising or hematoma. We report two cases of AH in neonates; the first presented with scrotal hematoma and the second with adrenal mass associated with hypertension and oliguria, primarily secondary to coincidental renal vein thrombosis. Diagnosis was confirmed by abdominal ultrasound. Patients were managed conservatively with clinical observation and by following hemoglobin and bilirubin levels closely. Both infants were discharged without surgical intervention after several days in the hospital. Clinicians should consider AH when a newborn presents with scrotal bruising or hematoma, unexplained anemia, unexplained jaundice, or flank abdominal mass. Timely ultrasonographic evaluation of both adrenal glands and testes in neonates with scrotal hematoma may spare infants from unnecessary surgical intervention because scrotal hematoma often raises the suspicion of testicular torsion. PMID- 26802637 TI - Emollient Use in the Term Newborn: A Literature Review. AB - The skin of a term newborn differs both from preterm skin and that of an adult, and there is currently little consensus on the proper use of emollients in this population. The focus of most published literature is on preterm skin and the use of bathing products, with limited information regarding emollient use. Intact skin is the first line of defense against infection, allergens, and dehydration, and dry and compromised skin puts the infant at greater risk of harm from the aforementioned complications. Emollients are part of the front-line treatment for atopic dermatitis (AD), and, with the incidence of AD on the rise, it is imperative that further research be conducted to provide a guide for clinical practice. PMID- 26802638 TI - Respiratory Development and Respiratory Distress Syndrome. AB - Respiratory development is crucial for all newborn infants. Premature infants may be born at an early stage of development and lack sufficient surfactant production. This results in respiratory distress syndrome. This article reviews the normal fetal development of the lung as well as the disorder that develops because of an early birth. PMID- 26802639 TI - Pharmacologic Management of Neonatal Seizures. AB - Seizures are most often the only sign of a central nervous dysfunction in the neonate. Neonatal seizures are a symptom of a specific disease entity. The search for a cause of neonatal seizures should focus on perinatal history or acute metabolic changes in the neonate. There are four classifications of neonatal seizures: clonic, tonic, myoclonic, and subtle. Simultaneous electroencephalogram and video recording are tools to assist the practitioner in the evaluation of difficult-to-assess subtle behaviors. Although many seizures may be prevented by careful attention to metabolic changes and the neonate's overall condition, those that cannot be prevented may require pharmacologic treatment. First-generation antiepileptic drugs such as phenobarbital and phenytoin are still the first and second lines of therapy, even as questions concerning their limited clinical effectiveness and concern for potential neurotoxicity continue. PMID- 26802640 TI - Quality Appraisal: Part I. AB - Quality appraisal is an essential step in the evidence-based practice process. This column focuses on designating the level of evidence of the scientific research. PMID- 26802642 TI - News of the Academy of Neonatal Nursing. PMID- 26802644 TI - What Is the Optimal Dose and Schedule for Dasatinib in Chronic Myeloid Leukemia: Two Case Reports and Review of the Literature. AB - Efficacy and safety of dasatinib in chronic phase (CP) chronic myelogenous leukemia (CML) patients has been well established. Initially approved dose and schedule of 70 mg twice daily has been changed to 100 mg once daily after demonstration of the same efficacy with less toxicity. Some patients require significant dose reductions to enable continued treatment with dasatinib. Even at a dose of 80 mg once daily, several patients may require further dose reductions due to substantial toxicity while maintaining good control of their disease. We report two CP-CML patients achieving and maintaining major molecular responses while on very low doses of dasatinib, ultimately achieving undetectable levels of BCR-ABL fusion transcript in their peripheral blood. Observations of several CP CML cases responding remarkably well to dasatinib despite very low dose and frequent dose interruptions challenge our current understanding and the accuracy of the data regarding the optimum dose and schedule of this drug. In selected intolerant patients, low-dose dasatinib therapy may be a safe and effective alternative treatment option before a treatment discontinuation or change considered. PMID- 26802645 TI - Knockdown of Legumain Suppresses Cervical Cancer Cell Migration and Invasion. AB - Cervical cancer is the second leading type of cancer in women living in less developed countries. The pathological and molecular mechanisms of cervical cancer are not comprehensively known. Though legumain has been found to be highly expressed in various types of solid tumors, its expression and biological function in cervical cancer remain unknown. In this study, we aimed to investigate legumain expression and functions in cervical cancer. We found that legumain was highly expressed in cervical cancer cells. When knocked down, legumain expression in HeLa and SiHa cells significantly reduced its migration and invasion abilities compared with control cells. Furthermore, legumain silencing suppressed the activation of matrix metalloproteases (MMP2 and MMP3) in cervical cancer cells. This study indicates that legumain might play an important role in cervical cancer cell migration and invasion. Legumain might be a potential therapeutic target for cervical cancer therapy. PMID- 26802643 TI - SQ grass sublingual allergy immunotherapy tablet for disease-modifying treatment of grass pollen allergic rhinoconjunctivitis. AB - BACKGROUND: Allergy immunotherapy is a treatment option for allergic rhinoconjunctivitis (ARC). It is unique compared with pharmacotherapy in that it modifies the immunologic pathways that elicit an allergic response. The SQ Timothy grass sublingual immunotherapy (SLIT) tablet is approved in North America and throughout Europe for the treatment of adults and children (>=5 years old) with grass pollen-induced ARC. OBJECTIVE: The clinical evidence for the use of SQ grass SLIT-tablet as a disease-modifying treatment for grass pollen ARC is discussed in this review. METHODS: The review included the suitability of SQ grass SLIT-tablet for patients with clinically relevant symptoms to multiple Pooideae grass species, single-season efficacy, safety, adherence, coseasonal initiation, and cost-effectiveness. The data from the long-term SQ grass SLIT tablet clinical trial that evaluated a clinical effect 2 years after a continuous 3-year treatment period were presented in the context of regulatory criteria that define a clinically meaningful effect. RESULTS: This trial demonstrated that the clinical effect of the SQ grass SLIT-tablet is maintained, which is also supported by the immunologic findings. CONCLUSION: Therefore, the SQ grass SLIT tablet has an indication as a disease-modifying therapy in Europe, and a sustained effect is recognized in the United States. PMID- 26802646 TI - Tumor-Suppressor Gene NBPF1 Inhibits Invasion and PI3K/mTOR Signaling in Cervical Cancer Cells. AB - The purpose of this study was to assess the effects of NBPF1 expression on cervical cancer cell invasion and apoptosis and to illustrate its potential mechanism. Human cervical cancer HeLa cells were transfected with the constructed siNBPF1 or pcDNA3.1-NBPF1 vectors. Effects of NBPF1 expression on cell invasion ability and cell apoptosis were analyzed using the Matrigel method and an Annexin V-FITC cell apoptosis kit, respectively. In addition, cell apoptosis-related proteins involved with the PI3K/mTOR signaling pathway were analyzed using Western blot. Remediation experiments were conducted to verify the effects of NBPF1 expression on cell invasion and apoptosis. Compared to the control, mRNA and protein expressions of NBPF1 were significantly decreased when cells were transfected with siNBPF1 (p < 0.05), which was contrary to the results of cells transfected with pcDNA3.1-NBPF1. Overexpression of NBPF1 significantly suppressed HeLa cell invasion but promoted cell apoptosis (p < 0.05). Overexpression of NBPF1 performed a significant inhibitory role on PI3K/mTOR signal pathway expression, while NBPF1 was silenced, showing contrary results. Our data suggested that NBPF1 overexpression may be a suppressor for cervical cancer via affecting cell invasion and apoptosis through regulating PI3K/mTOR signaling pathway. NBPF1 may be a potential therapeutic target for cervical cancer treatment. PMID- 26802647 TI - Inhibition of NF-kappaB Activity Enhances Sensitivity to Anticancer Drugs in Cholangiocarcinoma Cells. AB - Cholangiocarcinoma (CCA) is a dismal cancer. At present, there is no effective chemotherapeutic regimen for CCA. This may be due to the marked resistance of CCA to chemotherapy drugs, for which a mechanism remains unknown. Nuclear factor kappaB (NF-kappaB) is constitutively activated in a variety of cancer cells, including CCA. It has been shown to play roles in growth, metastasis, and chemoresistance of cancer. In the present study, we examined whether NF-kappaB is involved in the chemoresistance of CCA and whether dehydroxymethylepoxyquinomicin (DHMEQ), an effective NF-kappaB inhibitor, can overcome the drug resistance of CCA. Two CCA cell lines, KKU-M213 and KKU-M214, were treated with DHMEQ and/or chemotherapeutic drugs. Cell viability, apoptosis, and the expressions of the ATP binding cassette (ABC) transporters were compared. The combination of chemotherapy drugs, 5-fluorouracil, cisplatin, and doxorubicin, with DHMEQ significantly enhanced the cytotoxicity of all chemotherapeutic drugs compared to DHMEQ or drug alone. Furthermore, the mRNA level of ABCB1, a multidrug-resistant protein, was significantly decreased in the 5-fluorouracil combined with DHMEQ treated cells. These findings suggest that the inhibition of NF-kappaB by DHMEQ enhanced the chemoresponsiveness of CCA cells, possibly by reducing the expression of ABC transporter. Inhibition of NF-kappaB may be a potential chemodrug-sensitizing strategy for chemoresistant cancer such as CCA. PMID- 26802648 TI - Curcumin Enhances the Effects of 5-Fluorouracil and Oxaliplatin in Inducing Gastric Cancer Cell Apoptosis Both In Vitro and In Vivo. AB - Despite the efficacy of fluoropyrimidines and oxaliplatin-based chemotherapy for patients, this treatment leads to significant patient inconvenience, toxicity, and cost. This study aims to validate a nontoxic agent, curcumin, to the current chemotherapeutic regimen. In in vitro experiments, curcumin induced apoptosis in gastric cancer cell line BGC-823. Synergistic antitumor effects of curcumin were observed in combination with 5-fluorouracil (5-FU) and oxaliplatin. These effects were accompanied by downregulation of the expression of Bcl-2 protein and mRNA and upregulation of the expression of Bax and caspase 3, 8, and 9. In addition, the in vivo study showed that the combination of curcumin and 5-FU/oxaliplatin exhibited potent growth inhibition of BGC-823 xenograft tumors. Furthermore, compared with the control group, no significant difference was observed in the body weight of curcumin-treated nude mice. In conclusion, curcumin may act synergistically with the chemotherapeutic regimen FOLFOX in gastric cancer in vitro and in vivo by inducing apoptosis via Bcl/Bax-caspase 8,9-caspase 3 pathway. PMID- 26802649 TI - Enhancement of Chemosensitivity by Stathmin-1 Silencing in Gastric Cancer Cells In Situ and In Vivo. AB - Reports show that the stathmin gene may have a close relationship with tumor chemotherapeutic sensitivity. However, the effect of stathmin-1 on the chemosensitivity of gastric cancer to docetaxel has not been clearly determined. siRNA targeting stathmin-1 was introduced. The cell growth inhibition, expression of associated proteins, cell cycle, and apoptosis were evaluated by MTT, Western blot, and flow cytometric assays, respectively. The influence of silencing stathmin-1 was detected in situ and in vivo. SGC7901/docetaxel cells are the drug resistant cells. After silencing stathmin-1, the resistance index (RI) reduced to 3.41, the expressions of STMN-1, MDR1, and ERCC1 were downregulated, but caspase 3 was upregulated. Stathmin-1 siRNA could improve the chemosensitivity of gastric cancer cells to docetaxel, making the percentage of cells at the sub-G1 stage increase and promote apoptosis. The growth of transplantation tumor was significantly suppressed. Therefore, stathmin-1 might be a potential target for enhancing the chemosensitivity of gastric cancer. PMID- 26802650 TI - Overexpression of NDRG2 Increases Iodine Uptake and Inhibits Thyroid Carcinoma Cell Growth In Situ and In Vivo. AB - Medullary thyroid carcinoma (MTC) is an uncommon and highly aggressive tumor of the neuroendocrine system, which derives from the neuroendocrine C cells of the thyroid gland. Except for surgical resection, there are not very many effective systemic treatment options for MTC. N-Myc downstream-regulated gene 2 (NDRG2) had a significantly lower expression in MTC compared with normal thyroid tissue. However, the function of NDRG2 in MTC oncogenesis is largely unknown. In this study, we found that overexpression of NDRG2 inhibited the proliferation of TT cells (human medullary thyroid carcinoma cells) in vitro and suppressed the development of MTC in a nude mouse xenograft model. Further analysis revealed that NDRG2 arrested the cell cycle G0/G1 phase progression and induced TT cell apoptosis. Moreover, NDRG2 overexpression may mediate the antiproliferative effect by reducing cyclin D1 and cyclin E protein levels. We also found aberrant NDRG2-mitigated TT cell migration and invasion in vitro. Sodium/iodide symporter (NIS) mediates active I(-) transport into the thyroid follicular cells, and radionuclide treatment is a promising therapy for MTC. Our current data revealed that NDRG2 overexpression enhanced NIS level in TT cells and increased their iodine uptake in vitro. Furthermore, (99m)TcO4(-) radionuclide imaging of the xenograft tumors indicated that NDRG2 could promote NIS-mediated radionuclide transport. In conclusion, the present study suggested that NDRG2 is a critical molecule in the regulation of MTC biological behavior and a potential promoter in radioactive iodine therapy. PMID- 26802651 TI - Inhibition of Lung Carcinoma A549 Cell Growth by Knockdown of Hexokinase 2 In Situ and In Vivo. AB - Hexokinase 2 (HK2) has been identified as an oncogene in some malignant diseases such as breast cancer and ovarian cancer. However, the role of HK2 in lung cancer remains unclear. In this study, we explored the functional role of HK2 in lung cancer cell proliferation and tumorigenesis and determine its expression profile in lung cancer. HK2 expression was increased in primary lung cancer tissues of patients. Knocking down HK2 expression by small interfering RNA (siRNA) inhibited cell proliferation in lung cancer cells and nude mice. Thus, HK2 is required for sustained proliferation and survival of tumor cells in vitro and in vivo, and its aberrant expression may contribute to the pathogenesis of lung cancer. Thus, our study provided evidence that HK2 functions as a novel oncogene in lung cancer and may be a potential therapeutic target for lung cancer. PMID- 26802652 TI - Reduced PDCD4 Expression Promotes Cell Growth Through PI3K/Akt Signaling in Non Small Cell Lung Cancer. AB - It is largely recognized that PDCD4 is frequently lost in tumors of various origins, including lung cancer, and its loss contributes to tumor progression. However, its role and molecular mechanism remain largely unexplored in non-small cell lung cancer (NSCLC). In this study, downregulated PDCD4 mRNA expression was found in NSCLC tissues compared to their corresponding paracarcinoma tissues and distal paracarcinoma tissues. Induced expression of PDCD4 inhibited cell growth and proliferation and cell cycle transition in vitro. Conversely, knocking down PDCD4 expression promoted cell growth and proliferation. Mechanistically, PDCD4 inactivated PI3K/Akt signaling and its downstream cell cycle factors CCND1 and CDK4 to regulate cell growth in NSCLC. Additionally, PI3K-specific inhibitor Ly294002 suppressed the expression of pPI3K (Tyr458), pAkt (Ser473), CCND1, and CDK4 in PC9-shPDCD4 and A549-shPDCD4 cells. Furthermore, Akt-specific inhibitor MK2206 inhibited the expression of pAkt (Ser473), CCND1, and CDK4 in PC9-shPDCD4 and A549-shPDCD4 cells. Taken together, our study provides evidence that PDCD4 inhibits cell growth through PI3K/Akt signaling in NSCLC and may be a potential therapeutic target for NSCLC. PMID- 26802653 TI - Knockdown of microRNA-29a Changes the Expression of Heat Shock Proteins in Breast Carcinoma MCF-7 Cells. AB - Breast cancer is the most commonly occurring cancer among women. MicroRNAs as noncoding small RNA molecules play pivotal roles in cancer-related biological processes. Increased levels of microRNA-29a in the serum of breast cancer patients have been reported. Since heat shock proteins (HSPs) play important roles in cell events, the quantitative fluctuations in their cellular levels could be deemed as key indicators of how the exerted treatment alters cell behavior. In this regard, using an antisense small RNA, we attempted to investigate the effects of miR-29a knockdown on the expression of HSPs genes in the MCF-7 breast cancer cell line. MCF-7 cells were cultured in high-glucose Dulbecco's modified Eagle's medium with 10% FBS. Studied cells were subdivided into five groups: treated with scramble, anti-miR-29a, anti-miR-29a + Taxol, Taxol, and control. Taxol was added 24 h post-anti-miR transfection and RNA extraction, and cDNA synthesis was done 48 h later. The changes in expression of HSP27, HSP40, HSP60, HSP70, and HSP90 were evaluated by real-time PCR. Our results revealed that inhibitors of microRNA-29a promote apoptosis through upregulation of HSP60 level and downregulation of HSP27, HSP40, HSP70, and HSP90 levels and could be contemplated as a compelling alternative for Taxol employment with similar effects and/or to sensitize cancer cells to chemotherapy with fewer side effects. PMID- 26802654 TI - Apoptotic Melanoma B16-F1 Cells Induced by Lidamycin Could Initiate the Antitumor Immune Response in BABL/c Mice. AB - In the process of tumor cell apoptosis induced by specific regents, calreticulin (CRT) was transferred from endoplasmic reticulum (ER) onto the cell membrane. These tumor cells, when used as the cellular vaccine to immunize experimental animals, could initiate effective antitumor immunoresponse against homologous tumor cells. This is referred to as immunogenic cell death. Lidamycin (LDM) is an enediyne antibiotic, which has extremely potent cytotoxicity to cancer cells. In this study, the mouse melanoma B16-F1 cancer cells were used to investigate the ability of LDM in promoting immunogenic cell death. Our data showed that LDM could induce apoptosis of B16-F1 cancer cells, accompanied by CRT translocation onto the cell membrane. These LDM-treated B16-F1 cells could be recognized and phagocytosed more efficiently by macrophage and dendritic cells. When the LDM treated apoptotic B16-F1 cells were used as a whole-cell tumor vaccine to immune mice, the mice obtained resistance against rechallenged B16-F1 living cells. At the same time, the specific antitumor immune response was observed in these vaccinated mice. The splenocytes from the mice vaccinated with LDM-treated B16-F1 cells showed significantly enhanced NK lymphocyte activities and also faster growth rate and increased secretion of IFN-gamma when encountering the cellular antigens from B16-F1 cells. All these results suggested that LDM could promote immunogenic cell death in B16-F1 cells, and these LDM-treated B16-F1 cells could be used as a sort of cell vaccine to initiate effective antitumor immunoresponse in mice. PMID- 26802673 TI - Evaluation of immune responses induced by rhoptry protein 5 and rhoptry protein 7 DNA vaccines against Toxoplasma gondii. AB - Infection with the protozoan parasite Toxoplasma gondii is widespread, and the organism can cause congenital infections in humans. The horizontal transmission of Toxoplasma is even more common than congenital. An effective vaccine strategy brings the prospect of improving Toxoplasma disease control. Rhoptry protein 5 (ROP5) and ROP7 are potential stimulators of humoral and cellular immune responses. In this study, we constructed a multi-antigenic DNA vaccine expressing ROP5 and ROP7 of T. gondii and compared the protective efficacy to single-gene vaccines and control groups. BALB/c mice were immunized intramuscularly three times. The levels of IgG antibodies and cytokines in mice immunized with the multi-antigenic DNA vaccine (pROP5/ROP7) were significantly higher than those in the control mice. Mice vaccinated with pROP5/ROP7 showed a longer survival time (16 days) than single-gene-immunized mice (11 and 12 days, respectively) or control mice (8 days) after a challenge with 1 * 10(4) tachyzoites of RH strain of T. gondii. Furthermore, after intragastric infection with 20 cysts of PRU strain of T. gondii, the number of brain cysts in mice immunized with pROP5/ROP7 was only 25% of the number in control mice. Our results showed that a DNA vaccine encoding ROP5 and ROP7 significantly enhanced protection against T. gondii challenge. PMID- 26802674 TI - Artificial intelligence and synthetic biology: A tri-temporal contribution. AB - Artificial intelligence can make numerous contributions to synthetic biology. I would like to suggest three that are related to the past, present and future of artificial intelligence. From the past, works in biology and artificial systems by Turing and von Neumann prove highly interesting to explore within the new framework of synthetic biology, especially with regard to the notions of self modification and self-replication and their links to emergence and the bottom-up approach. The current epistemological inquiry into emergence and research on swarm intelligence, superorganisms and biologically inspired cognitive architecture may lead to new achievements on the possibilities of synthetic biology in explaining cognitive processes. Finally, the present-day discussion on the future of artificial intelligence and the rise of superintelligence may point to some research trends for the future of synthetic biology and help to better define the boundary of notions such as "life", "cognition", "artificial" and "natural", as well as their interconnections in theoretical synthetic biology. PMID- 26802675 TI - Ephaptic transmission from type ii afferents to static gamma and beta efferents causes complex repetitive discharge: An hypothesis. AB - INTRODUCTION: Complex repetitive discharges (CRDs) are thought to result from depolarization of a single denervated muscle fiber, followed by ephaptic spread to adjacent fibers. This leads to cyclic spread of the depolarization to produce a recurrent discharge. Another explanation is suggested. METHODS: CRDs were recorded with single and multiple electromyographic needles longitudinal to muscle fibers in 39 neuropathy patients. RESULTS: The mean frequency of CRDs was 26 Hz, mean number of negative spikes was 5.4, and blocking of spikes occurred in 53% of CRDs. In multi-needle recordings most CRDs were local, but propagation of the discharge was sometimes observed. CONCLUSIONS: The prevailing hypothesis of CRDs cannot explain local CRDs. Type II afferents of bag2 and chain fibers branch widely in the juxtaequatorial region of muscle spindles where they may intermingle with motor terminals. Ephaptic transmission from type II afferents to static gamma and beta efferents may cause CRDs and fix the CRD frequency. PMID- 26802676 TI - Role of quercetin on Caco-2 cells against cytotoxic effects of alternariol and alternariol monomethyl ether. AB - Molds of the genus Alternaria have been reported as contaminants of a variety of food and feed. Alternaria toxins such as alternariol (AOH) and its naturally occurring monomethyl ether (AME) produce cytotoxicity and oxidative stress in cell cultures. On the other hand, it has been proved that natural polyphenols have antioxidant effect. Quercetin (Quer) is a polyphenol present in berries and other commodities which exhibits these effects. The aims were to evaluate the cytotoxicity of AOH, AME and the binary combination of them, and the cytoprotective effect of Quer exposed simultaneously with AOH, AME and the mycotoxin mixture in human adenocarcinoma (Caco-2) cells. The cytotoxicity and the cytoprotective effect were determined by the MTT test after 24 and 48 h of exposure and interactions were evaluated with the isobologram analysis method. Cell viability decreased after 48 h of AOH and AME exposures, being the binary combination more cytotoxic, causing a synergism effect. No cytoprotective effect of Quer against AOH and AME was observed when they were exposed simultaneously in Caco-2 cells. The cytoprotective effect of Quer against mycotoxins (AOH, AME or other different which could present higher cytotoxic effect) depends on the concentration, the presence and the interaction between the compounds in food. PMID- 26802678 TI - Cytotoxic effects induced by patulin, sterigmatocystin and beauvericin on CHO-K1 cells. AB - Mycotoxins are produced by different genera of fungi; mainly Aspergillus, Penicillium and Fusarium. The natural co-occurrence of beauvericin (BEA), patulin (PAT) and sterigmatocystin (STE) has been proved in feed and food commodities. This study investigates the cytotoxicity of individual and combined mycotoxins BEA, PAT and STE. The cytotoxicity on immortalized ovarian cells (CHO-K1) was evaluated using the MTT assay. After 24, 48 and 72 h, the IC50 values were 2.9 MUM for PAT and ranged from 10.7 to 2.2 MUM and from 25.0 to 12.5 MUM for BEA and STE, respectively. Cytotoxic interactions were assayed by the isobologram method, which provides a combination index (CI) value as a quantitative measure of the three mycotoxin interaction's degree. Binary and tertiary combinations showed a dose dependent effect. At low fraction affected, mycotoxin combinations were synergetic; whereas, at higher fraction affected, the combinations showed additive effect. Our results indicate that the co-occurrence of low concentrations of mycotoxin in food may increase their toxic effects. PMID- 26802677 TI - Investigation of the genotoxicity of substances migrating from polycarbonate replacement baby bottles to identify chemicals of high concern. AB - Due to the worldwide concern that bisphenol A might act as an endocrine disruptor, alternative materials for polycarbonate (PC) have been introduced on the European market. However, PC-replacement products might also release substances of which the toxicological profile--including their genotoxic effects- has not yet been characterized. Because a thorough characterization of the genotoxic profile of all these substances is impossible in the short term, a strategy was developed in order to prioritize those substances for which additional data are urgently needed. The strategy consisted of a decision tree using hazard information related to genotoxicity. The relevant information was obtained from the database of the European Chemicals Agency (ECHA), in silico prediction tools (ToxTree and Derek Nexus(TM)) and the in vitro Vitotox((r)) test for detecting DNA damage. By applying the decision tree, substances could be classified into different groups, each characterized by a different probability to induce genotoxic effects. Although none of the investigated substances could be unequivocally identified as genotoxic, the presence of genotoxic effects could neither be excluded for any of them. Consequently, all substances require more data to investigate the genotoxic potential. However, the type and the urge for these data differs among the substances. PMID- 26802679 TI - Sex differences in genetic and environmental contributions to alcohol consumption from early adolescence to young adulthood. AB - AIMS: To estimate genetic and environmental contributions to alcohol consumption from early adolescence to young adulthood, and test whether gender moderates these effects. DESIGN: Longitudinal twin cohort design. SETTING: Population-based sample from Norway. PARTICIPANTS: A total of 2862 male and female twins, aged 14 22 years, were assessed at one (n = 881), two (n = 898) or three (n = 1083) occasions. The percentage of females was between 56 and 63 in the different age groups (in the different waves). MEASUREMENTS: Alcohol consumption was measured by two questionnaire items about frequency of alcohol use and frequency of being drunk. FINDINGS: Additive genetic effects showed low to moderate contributions [proportion estimate, 95% confidence interval (CI) = range from 0.03 (0.00-0.14) to 0.49 (0.37-0.59) in males and from 0.09 (0.00-0.57) to 0.41 (0.24-0.58) in females] from adolescence to young adulthood, while environmental influences shared by twin pairs and contributing to twin similarity were moderate to highly influential during this developmental period [proportion estimate, 95% CI = range from 0.04 (0.00-0.13) to 0.45 (0.26-0.60) in males for shared environment in common with females, from 0.25 (0.09-0.42) to 0.54 (0.06-0.78) for shared environment specific to males and from 0.36 (0.20-0.52) to 0.51 (0.37-0.71) in females]. There was evidence of qualitative sex differences with shared environmental influences being largely sex-specific from middle adolescence onwards. CONCLUSIONS: Alcohol consumption from early adolescence to young adulthood appears to be influenced to a small to moderate degree by genetic factors and to a moderate to high degree by shared environmental factors (e.g. rearing influences, shared friends). The shared environmental factors influencing alcohol consumption appear to be largely gender-specific. PMID- 26802680 TI - Human cell lines: A promising alternative for recombinant FIX production. AB - Factor IX (FIX) is a vitamin K-dependent protein, and it has become a valuable pharmaceutical in the Hemophilia B treatment. We evaluated the potential of recombinant human FIX (rhFIX) expression in 293T and SK-Hep-1 human cell lines. SK-Hep-1-FIX cells produced higher levels of biologically active protein. The growth profile of 293T-FIX cells was not influenced by lentiviral integration number into the cellular genome. SK-Hep-1-FIX cells showed a significantly lower growth rate than SK-Hep-1 cells. gamma-carboxylation process is significant to FIX biological activity, thus we performed a expression analysis of genes involved in this process. The 293T gene expression suggests that this cell line could efficiently carboxylate FIX, however only 28% of the total secreted protein is active. SK-Hep-1 cells did not express high amounts of VKORC1 and carboxylase, but this cell line secreted large amounts of active protein. Enrichment of culture medium with Ca(+2) and Mg(+2) ions did not affect positively rhFIX expression in SK-Hep-1 cells. In 293T cells, the addition of 0.5 mM Ca(+2) and 1 mM Mg(+2) resulted in higher rhFIX concentration. SK-Hep-1 cell line proved to be very effective in rhFIX production, and it can be used as a novel biotechnological platform for the production of recombinant proteins. PMID- 26802681 TI - Recombinant production and purification of short hydrophobic Elastin-like polypeptides with low transition temperatures. AB - Elastin-like polypeptides (ELPs) are biodegradable polymers with interesting physico-chemical properties for biomedical and biotechnological applications. We report herein the recombinant expression of three hydrophobic ELPs (VPGIG)n with variable lengths (n = 20, 40, 60) and sub-ambient transition temperatures. These ELPs were purified from the cytoplasmic soluble fraction of Escherichia coli by inverse transition cycling, and their exact molecular weight was confirmed by various mass spectrometry techniques. Transition temperatures of ELP20, ELP40, and ELP60 were measured at 18.6 degrees C, 12.4 degrees C and 11.7 degrees C, respectively. PMID- 26802682 TI - Phenobarbital use and neurological problems in FMR1 premutation carriers. AB - Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by a CGG expansion in the FMR1 gene located at Xq27.3. Patients with the premutation in FMR1 present specific clinical problems associated with the number of CGG repeats (55-200 CGG repeats). Premutation carriers have elevated FMR1 mRNA expression levels, which have been associated with neurotoxicity potentially causing neurodevelopmental problems or neurological problems associated with aging. However, cognitive impairments or neurological problems may also be related to increased vulnerability of premutation carriers to neurotoxicants, including phenobarbital. Here we present a study of three sisters with the premutation who were exposed differentially to phenobarbital therapy throughout their lives, allowing us to compare the neurological effects of this drug in these patients. PMID- 26802683 TI - Evaluation of a commercial real-time PCR kit for the detection of the Q80K polymorphism in plasma from HCV genotype 1a infected patients. AB - BACKGROUND: Screening of the natural HCV NS3 polymorphism Q80K is required prior to simeprevir administration due to the reduced susceptibility of genotype 1 viruses carrying this amino acid variant. A simple, rapid and robust test for Q80K screening would be advisable in routine diagnostic laboratories. OBJECTIVES: The aim of this study was to evaluate a commercial NS3 Q80K real-time PCR kit (Q80K Polymorphism Kit, Clonit srl, Milan, Italy). STUDY DESIGN: Forty-three plasma samples obtained from untreated HCV genotype 1a-infected patients and previously sequenced at a reference laboratory, were sent to two public clinical virology laboratories for blinded Q80K screening with the kit under evaluation. The sample panel included 25 cases with the wild type 80Q, 17 with the mutant 80K and 1 with the mutant 80L. RESULTS: Laboratory 1 identified 22/25 (88.0%) 80Q and 17/17 (100.0%) 80K cases. Laboratory 2 identified 23/25 (92.0%) 80Q and 16/17 (94.2%) 80K cases. All of the unidentified cases were scored as negative, with no mutant/wild type miscalling. The 80L variant was scored as indeterminate by Laboratory 1 and as negative by Laboratory 2. Overall, sensitivity and specificity for detection of 80K were 97.1% (95% C.I., 82.9-99.8%) and 100.0% (90.2-100.0%), respectively. However, the system did not provide any result for 6/84 cases (7.1% failure rate), not including the 80L variant which is not expected to be detected as stated in the kit package insert. Global inter laboratory concordance was 93.0%. CONCLUSIONS: Despite good specificity, this Q80K detection system needs improvements in amplification success rate and robustness. PMID- 26802685 TI - [Alcohol--when it's beneficial to your health?]. AB - Ethyl alcohol is the most commonly used psychoactive agent. It's average consumption in Poland totaled 9.67 liters per capita in 2013. Ethanol's biotransformation rate in an adult ranges from 7 to 10 grams per hour. The basic metabolism takes place in the liver through the oxidation involving NAD+. The alcohol is transformed first into acetaldehyde and then into acetic acid. In higher blood concentrations or in alcoholism, cytochrome's P-450 coenzyme CYP2E1 also plays an important role in this process. Alcohol is responsible for nearly 50% of annual deaths, mostly caused by an accident due to alcohol intoxication while driving. Studies were performed to determine the influence ethanol has on the human body and how it impacts the progression of illnesses such as senile dementia, cardiovascular diseases or osteoporosis. Scientists' attention was drawn to the possibility of ethyl alcohol's usage resulting in a reduction in an overall mortality rate, however the beneficial effects were observed only during a slight and moderate consumption. Higher doses of alcohol were associated with a decline in patient's condition. The purpose of this dissertation is an attempt to answer the question, whether the alcohol can be beneficial to the user's health and if so, in what doses? The importance of this topic comes from the fact that due to the alcohol being widely available, determining the influence it has on human body is vital for public health. Original articles and reviews were used to summarize the results of studies regarding the topic. PMID- 26802686 TI - What does impedance cardiography add more to the assessment of left ventricular diastolic function in essential hypertension? AB - Left ventricular diastolic dysfunction (LVDdf) and arterial stiffness are associated with increased mortality in patients with arterial hypertension. THE AIM: of the study was to evaluate the relation between left ventricular diastolic function and hemodynamic profile assessed by impedance cardiography (ICG). MATERIAL AND METHODS: In 209 hypertensives clinical evaluation, echocardiography and ICG were performed to evaluate i.e. septal annulus early diastolic velocity (e'), mitral flow ratio (E/A), stroke index (SI), acceleration index (ACI), velocity index (VI), Heather index (HI), total arterial compliance. RESULTS: Left ventricular diastolic dysfunction was associated with lower SI (p=0.049), VI (p=0.002), ACI (p=0.014), HI (p=0.002) and higher SVRI (p=0.004). There were no significant differences in age, blood pressure, BMI, sex distribution. Males with LVDdf characterized with lower SI (p=0.011), VI (p<0.00001), ACI (p=0.0005), HI (p=0.00005) and higher SVRI (p=0.008). No such relevant differences were observed in women. In the analysis of the relations between clinical/hemodynamic features and echocardiographic indices of left ventricular diastolic function the significant correlations were observed in males, the most relevant for: age vs E/A (-0.45; p<0.001), VI vs e' (0.30; p<0.001), VI vs E/A (0.30; p<0.001), and SVRI vs e' (-0.28; p<0.001). CONCLUSIONS: Impedance cardiography revealed to be useful in the evaluation of impaired left ventricular performance and increased arterial stiffness related to LVDdf in young and middle-aged hypertensives. Sex may influence cardiovascular hemodynamics resulting in slightly different ventricular-vascular interactions that should be considered in therapeutic strategies. PMID- 26802684 TI - Relationship Between Adolescent Report of Patient-Centered Care and of Quality of Primary Care. AB - OBJECTIVE: Few studies have examined adolescent self-report of patient-centered care (PCC). We investigated whether adolescent self-report of PCC varied by patient characteristics and whether receipt of PCC is associated with measures of adolescent primary care quality. METHODS: We analyzed cross-sectional data from Healthy Passages, a population-based survey of 4105 10th graders and their parents. Adolescent report of PCC was derived from 4 items. Adolescent primary care quality was assessed by measuring access to confidential care, screening for important adolescent health topics, unmet need, and overall rating of health care. We conducted weighted bivariate analyses and multivariate logistic regression models of the association of PCC with adolescent characteristics and primary care quality. RESULTS: Forty-seven percent of adolescents reported that they received PCC. Report of receiving PCC was associated with high quality for other measures, such as having a private conversation with a clinician (adjusted odds ratio [aOR] 2.2; 95% confidence interval [CI] [1.9, 2.6]) and having talked about health behaviors (aOR 1.6; 95% CI 1.4, 1.8); it was also associated with lower likelihood for self-reported unmet need for care (aOR 0.8; 95% CI 0.7, 0.9) and having a serious untreated health problem (aOR 0.4; 95% CI 0.3, 0.5). CONCLUSIONS: Many adolescents do not report receiving PCC. Adolescent-reported PCC positively correlates with measures of high-quality adolescent primary care. Our study provides support for using adolescent-report of PCC as a measure of adolescent primary care quality. PMID- 26802687 TI - [Patients with chronic obstructive pulmonary disease (COPD)--similarities and differences of the study group participating in the project of National Center for Research and Development project "Chronic obstructive pulmonary disease (COPD)--systemic disease, the biggest threat of XXI century"]. AB - Chronic obstructive pulmonary disease (COPD) is a significant clinical problem wich is dependent on many environmental factors. THE AIM: of the study was to present a characteristic of examined group in the moment of including into the project. MATERIALS AND METHODS: Based on data obtained from studies conducted in six medical universities in Poland we present the characteristics of 445 patients (M-69%), median age 66.2 years, suffering from COPD with median disease duration 7.7 years. The analysis included: age, education, risk factors, exacerbations and hospitalizations, comorbidities, severity of the disease, drug use and the results of selected tests and the quality of life of patients in relation with their place of residence. RESULTS: Some differences were found among the participating centers. The youngest patients came from Wroclaw and the oldest from Katowice. The largest number of patients with higher education were from Warsaw, while the lowest number was noted in Poznan; patients with primary education were most numerous in Lublin. Patients from Warsaw had the highest number of pack-years, smoking history was least relevant in patients from Wroclaw. The highest values of spirometrical parameters were observed in Gdansk, while the lowest--in Poznan. COPD treatment mainly comprised of long-acting beta2 agonists, followed by anticholinergic agents, more than 50% of patients were treated with inhaled glucocorticosteroids. The most common comorbidities were cardiovascular diseases. CONCLUSIONS: The study group showed characteristics similar to those of other cohorts of patients with COPD described in the literature, but we found some differences between patients from different centers which participated in the study. PMID- 26802688 TI - [Estimation of plasma 25(OH)D vitamin level in patients with metabolic syndrome]. AB - Cardiovascular diseases are a major public health problem in developed and developing countries. A number of recent studies point to the pleiotropic differentiated effects of vitamin D, the deficiency of which positively correlates with the increased risk for cardiovascular diseases, hypertension, dyslipidemia, obesity or metabolic syndrome (MS). Vitamin D deficiency has also been proven to affect the progression of atherosclerosis. THE AIM: of this study was to evaluate plasma 25(OH)D level in patients with MS. MATERIALS AND METHODS: The study included 268 patients with MS, 136 men and 132 women, aged 30-65 years (mean 59,62+/-9,21 years). The study group was divided according to the age and season. The concentration of 25-hydroxy vitamin D (25-OH-D) was assessed with the application of the LIAISON(r) test using chemiluminescent immunoassay (CLIA) technology. RESULTS: The mean plasma level of 25(OH)D was 14,56+/-7,81 ng/ml in MS patients and it was not significantly higher in women than men (15,14 +/-3,29 ng/ml vs. 13,97+/-3,41 ng/ml, p>0,05). The lowest 25(OH)D concentration was noted in the oldest age group (9,24+/-4,78 ng/ml). The highest 25(OH)D concentration was noted in summer months (23,71+/-3,82 ng/ml). CONCLUSIONS: The concentration of vitamin D in the plasma of patients with MS was significantly lower than its recommendations. Age and season of the year were the factors strongly affecting the level of 25(OH)D in MS patients. PMID- 26802689 TI - Assessment of body posture in 12- and 13-year-olds attending primary schools in Pabianice. AB - THE AIM: of study was to estimate the body posture in children finishing primary schools. This is the last moment to make any improvement in body posture needed, because after the end of the child's growth the correction of postural defects is practically impossible. MATERIALS AND METHODS: The study was conducted on 236 pupils aged 12-13 years attending primary schools number 3, 5 and 17 in Pabianice. To evaluate body posture Kasperczyk's points method was used. It is a commonly applied method for screening purposes. RESULTS: Over 50% of studied children had poor body posture and just under 6% of pupils' posture was assessed as very good. In the study population of children finishing primary schools the occurrence of faulty posture was shown to be very high. The most common defect in body posture among pupils was an uneven alignment of shoulders and shoulder blades. CONCLUSIONS: The results obtained in this study indicate the need to undertake action reducing the occurrence of faulty posture among children in Pabianice. PMID- 26802690 TI - [Long-term somatic consequences of intimate partner violence in primary care female patients]. AB - Violence against women has many various short- and long-term effects. Although violence by an intimate partner has been widely documented, still little is known about its long-term somatic consequences for the victim. THE AIM: of the study was to examine the prevalence of intimate partner violence (IPV) among patients seeing a general practitioner as well as to determine relationships between IPV and somatic complaints other than direct somatic consequences (such as injuries), including somatic diseases and healthcare services use. MATERIALS AND METHODS: The study sample comprised 151 women seeing a family doctor consecutively. The participants were administered a structured interview questionnaire developed for the purpose of this study. RESULTS: The prevalence of IPV for the total sample of primary health care female patients was 35.1% during 12 months preceding the examination. Compared to patients with no violence history, those experiencing IPV reported significantly more physical complaints and symptoms, particularly about cardiovascular, nervous, digestive and genitourinary systems. They were also at a higher risk of developing numerous diseases, with the greatest risk of peptic ulcer (OR, 6.62), and ischaemic heart disease (OR, 5.98). IPV victims were also more likely to seek help of a family doctor and the following specialists: neurologist (OR, 3.88), cardiologist (OR, 4.01), gastroenterologist (OR, 4.51), psychiatrist (OR, 2.43), endocrinologist (OR, 1.6), and pulmonologist (OR, 1.2). They were also more likely to use emergency department (OR, 3.23) and require hospitalization (OR, 3.61). CONCLUSIONS: It is recommended that the medical interview should include questions referring to violence, especially in case of patients reporting various symptoms about different systems and organs that have no medical explanation, or symptoms with intensity greater than it should be given the patients' actual physical state. PMID- 26802691 TI - [Septic shock in 23 year old female patient after surgical correction of the nasal septum effectively treated in the intensive care unit]. AB - A female patient 23 years old was admitted to the medical intensive care unit due to sudden loss of consciousness and seizures. At the time of admition observed lack of consciousness, seizures and severe critical condition was observed. Meningitis and septic shock were diagnosed. Based on computed tomography performed on the first day--inflammation of the sinuses soft tissues was diagnosed. Suspected cause of infection was performed 6 weeks earlier surgical correction of the nasal septum. In the next stage of treatment on the seventh day after admission the functional endoscopic sinus surgery was performed. Due to massive tissue hypoperfusion the necrosis in the skin of the lower limbs occurred. Due to the lack of effectiveness antimicrobial therapy use of intravenous ceftaroline was administrated. Effective treatment allowed in day 11 to wean the patient from the ventilator. At the day 26 the patient was transferred to a hospital in the place of residence. PMID- 26802692 TI - Acute clenbuterol overdose manifestations in a suicide attempt--a case report. AB - A 30-year-old man was admitted to the intensive care unit after a suicide attempt with respiratory difficulties, tremor, sinus tachycardia and significant hypokalemia. On examination, the patient was lucid, fully conscious and did not exhibit positive symptoms. Sings were not typical for overdosing olanzapine, alprazolam and alcohol as declared by the patient. Additional anamnesis revealed high doses of ingested clenbuterol, a selective beta2-adrenergic agonist. Due to its anabolic and lipolytic properties, clenbuterol has become a commonly abused drug in bodybuilding industry and is not routinely detected by toxicology screens. This is the first known report of suicide attempt by clenbuterol overdosing. PMID- 26802693 TI - [New definition of ventilator associated pneumonia might not necessarily have been a step in the right direction. Key takeaways from published studies after two years in clinical use]. AB - Ventilator-associated pneumonia (VAP) is one of the most common hospital-acquired infections. VAP is associated with prolonged hospitalization and visibly increased mortality, which in the group of patients with VAP ranges from 25% to 47%. In January 2013 Centers of Disease Control and Prevention introduced a new definition for VAP. Subjective criteria in the previous VAP definition were the reason for difficulties in VAP surveillance and assessment of efficacy of ventilator bundles and other quality improvement initiatives. The purpose of this article is to summarise the new definition of VAP and the first researches after two years of use of the new definition. The new definition of ventilator associated events (VAE) identifies a broader group of patients than the previous VAP definition. Surveillance of all complications of mechanical ventilation aimed to create more efficient prophylaxis bundles and to decrease the mortality in critically ill patients. The latest published studies suggest that most of the complications defined as VAE are patient-related, not modifiable risk factors and these patients had no evidence of hospital-acquired complications. The new definition failed to detect many patients with VAP and it has not resolved the ambiguities related to the diagnosis of this complication. It seems that the new surveillance program will not lead to introducing new prevention strategies that could decrease the mortality in intensive care unit patients. PMID- 26802694 TI - [Indicators of inflammatory process in stool in diagnostics and monitoring of inflammatory bowel diseases]. AB - In the recent decades the rapid development of the studies on new methods used in diagnosis, differential diagnosis, and monitoring the treatment of inflammatory bowel diseases has been observed. To the diagnostics of gastrointestinal disorders new methods such as endoscopic capsule and imaging methods including magnetic resonance have been introduced. Markers of inflammation detected in stool play significant role in the diagnostics. To the best known belong calprotectine and lactoferrin, which are produced by neutral granulocytes. In the present review we have presented the clinical usefulness of detection in the stool of calprotectin, lectoferrin, S100A12 protein and pyruvate kinase. Clinical usefulness of these markers were used in diagnosis, assessment of the treatment results, disease relapse and mucosal healing in inflammatory bowel disease. Determination of fecal calprotectin and lactoferrin in the process of mucosal healing in ulcerative colitis or Crohn's disease are of particular value. Confirmation of these results in multicenter prospective trials will enable in the future to reduce the number of control colonoscopies, which in children are performer under general anesthesia. PMID- 26802695 TI - [The role of the adaptive stress response in the pathogenesis of neurodegenerative diseases, cancer and diabetes mellitus type 2]. AB - The ER (Endoplasmatic Reticulum) an intricate intracellular membrane system is responsible for many functions within cells; including folding and post translational modifications of secretory proteins biosynthesis of ceramides, phospholipids and coordination of cell homeostasis. Perturbation of these ER processes leads to high levels unfolded and misfolded proteins within the lumen of the ER. These disturbances lead to activation of three primary receptors: PERK (Protein kinase RNA-like endoplasmic reticulum kinase), IRE1 (Inositol-Requiring Enzyme 1) and ATF6 (Activating Transcription Factor 6). These signal transducers are responsible for inducing signalling pathways termed UPR (Unfolded Protein Response) restoring cell homeostasis. In contrast, unresolved ER stress contributes to cell death by apoptosis. Recent research allows for a conclusion that the deregulation of UPR is the main causative factor for functional cell loss and moreover, cell death by apoptosis, which is strictly linked to the pathology of human diseases to include: cancer, diabetes mellitus type 2 and neurodegenerative diseases such as Alzheimer's, Parkinson's and prion diseases. PMID- 26802696 TI - [Pathogenesis and clinical manifestations of sporadic cerebral small vessel disease]. AB - Sporadic small vessel disease (sSVD) is one of the most common vascular disease of the central nervous system (CNS). It is the main cause of lacunar stokes, hemorrhages to deep brain regions and chronic CNS diseases such as vascular parkinsonism and dementia. Beside a high and growing incidence of sSVD especially in the elderly population, the knowledge of ethiopathogenesis and optimal treatment of sSVD have not been established. The article summarizes different clinical manifestations (acute and chronic) as well as heterogenous radiologic changes found in CNS neuroimaging. PMID- 26802697 TI - [The influence of breathing mode on the oral cavity]. AB - Nose breathing is one of the key factors in the proper development and functioning of the oral cavity. The air passing through the nasal cavity is warmed and humidified while dust and other particulate matter is removed. It is also important as far as bone formation is concerned. The obstruction or congestions of the upper respiratory tract may negatively affect the correct and most optimal (nasal) respiratory tract. The switch from nasal to mouth breathing may lead to serious clinical consequences. Children with the clinical diagnosis of mouth breathing are usually pale, apathetic and they lack concentration and often get tired. Disorders resulting from hypoxy may also be the reason from sleep disturbances, such as frequent waking-up, nocturia, difficulties falling aslee. The main clinical manifestations of mouth breathing appear in the craniofacial structures. Mouth breathers frequently suffer from dental malocclusions and craniofacial bone abnormalities. Chronic muscle tension around the oral cavity could result in the widening of cranio-vertebral angle, posterior position of mandibula and narrow maxillary arch. Among dental alterations the most common are class II malocclusion (total or partial) with the protrusion of the anterior teeth, cross bite (unilateral or bilateral), anterior open bite and primary crowded teeth. Apart from malocclusion, chronic gingivitis, periodontitis, candida infections and halitosis are frequently present in mouth- breathing patients. PMID- 26802699 TI - Radionuclide observables during the Integrated Field Exercise of the Comprehensive Nuclear-Test-Ban Treaty. AB - In 2014 the Preparatory Commission for the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO) undertook an Integrated Field Exercise (IFE14) in Jordan. The exercise consisted of a simulated 0.5-2 kT underground nuclear explosion triggering an On-site Inspection (OSI) to search for evidence of a Treaty violation. This research paper evaluates two of the OSI techniques used during the IFE14, laboratory-based gamma-spectrometry of soil samples and in-situ gamma spectrometry, both of which were implemented to search for 17 OSI relevant particulate radionuclides indicative of nuclear explosions. The detection sensitivity is evaluated using real IFE and model data. It indicates that higher sensitivity laboratory measurements are the optimum technique during the IFE and within the Treaty/Protocol-specified OSI timeframes. PMID- 26802698 TI - Resting state EEG correlates of memory consolidation. AB - Numerous studies demonstrate that post-training sleep benefits human memory. At the same time, emerging data suggest that other resting states may similarly facilitate consolidation. In order to identify the conditions under which non sleep resting states benefit memory, we conducted an EEG (electroencephalographic) study of verbal memory retention across 15min of eyes closed rest. Participants (n=26) listened to a short story and then either rested with their eyes closed, or else completed a distractor task for 15min. A delayed recall test was administered immediately following the rest period. We found, first, that quiet rest enhanced memory for the short story. Improved memory was associated with a particular EEG signature of increased slow oscillatory activity (<1Hz), in concert with reduced alpha (8-12Hz) activity. Mindwandering during the retention interval was also associated with improved memory. These observations suggest that a short period of quiet rest can facilitate memory, and that this may occur via an active process of consolidation supported by slow oscillatory EEG activity and characterized by decreased attention to the external environment. Slow oscillatory EEG rhythms are proposed to facilitate memory consolidation during sleep by promoting hippocampal-cortical communication. Our findings suggest that EEG slow oscillations could play a significant role in memory consolidation during other resting states as well. PMID- 26802700 TI - Compound high-quality criteria: a new vision to guide the development of drugs, current situation. AB - For several decades, the pharmaceutical industry has suffered due to major issues such as reductions of the number of FDA approved drugs and biologics. Several analyses have been highlighted that the 'druglikeness' is one of the strategies to improve succeed rates of screening such as, for instance, high-throughput screening (HTS), and then hits (as starting point), leads and clinical candidates. It is clear that the improvement of compound quality accelerates the drug discovery projects. The monitoring of several indices to avoid 'molecular obesity' (ADMET problems) of final drugs from good-quality 'low-fat' starting points represents today a powerful strategy of optimization process. The development of the new guides to find drugs highlighting attempts at improving the attrition rate from hits to final medicines by focusing on how to improve the druggability of hits, leads and drugs during the drug discovery process represents a key approach to design next better generation of medicines. PMID- 26802701 TI - Comparison of poly(epsilon-caprolactone) chain lengths of poly(epsilon caprolactone)-co-d-alpha-tocopheryl-poly(ethylene glycol) 1000 succinate nanoparticles for enhancement of quercetin delivery to SKBR3 breast cancer cells. AB - This study aimed to investigate the effect of the different hydrophobic chain lengths of poly(epsilon-caprolactone)-co-d-alpha-tocopheryl polyethylene glycol 1000 succinate (P(CL)-TPGS) copolymers on the nanoparticle properties and delivery efficiency of quercetin to SKBR3 breast cancer cells. The 5:1, 10:1 and 20:1 P(CL)-TPGS copolymers were fabricated and found to be composed of 25.0%, 45.2% and 66.8% of hydrophobic P(CL) chains with respect to the polymer chain, respectively. The DSC measurement indicated the microphase separation of P(CL) and TPGS segments. The crystallization of P(CL) segment occurred when the P(CL) chain was higher than 25% due to the restricted mobility of P(CL) by TPGS. The longer P(CL) chain had the higher crystallinity while decreasing the crystallinity of TPGS segment. The increasing P(CL) chain length increased the particle size of P(CL)-TPGS nanoparticles from 20 to 205 nm and enhanced the loading capacity of quercetin due to the more hydrophobicity of the nanoparticle core. The release of quercetin was retarded by an increase in P(CL) chain length associated with the increasing hydrophobicity and crystallinity of P(CL)-TPGS copolymers. The P(CL)-TPGS nanoparticles potentiated the toxicity of quercetin to SKBR3 cells by at least 2.9 times compared to the quercetin solution. The cellular uptake of P(CL)-TPGS nanoparticles by SKBR3 cells occurred through cholesterol-dependent endocytosis. The 10:1 P(CL)-TPGS nanoparticles showed the highest toxicity and uptake efficiency and could be potentially used for the delivery of quercetin to breast cancer cells. PMID- 26802702 TI - Intracameral Antibiotics Reduce the Risk of Endophthalmitis after Cataract Surgery: Does the Preponderance of the Evidence Mandate a Global Change in Practice? PMID- 26802703 TI - An Important Step Forward in Myopia Prevention: Low-Dose Atropine. PMID- 26802704 TI - Ophthalmomyiasis Interna. PMID- 26802705 TI - Nonlimbal Squamous Cell Carcinoma of the Conjunctiva. PMID- 26802706 TI - Bulbar Conjunctival Molluscum Contagiosum. PMID- 26802707 TI - Bilateral Peripapillary Racemose Hemangioma: An Unusual Presentation. PMID- 26802708 TI - Bilateral Optic Nerve Metastases. PMID- 26802709 TI - Limbal Mantle Cell Lymphoma of the Conjunctiva. PMID- 26802710 TI - Nasal Hemiretinal Vein Occlusion. PMID- 26802711 TI - Re: Francis et al.: The classification of vitreous seeds in retinoblastoma and response to intravitreal melphalan (Ophthalmology 2015;122:1173-9). PMID- 26802712 TI - Reply. PMID- 26802713 TI - Re: Sophie et al.: Predictors of functional and anatomic outcomes in patients with diabetic macular edema treated with ranibizumab (Ophthalmology 2015;122:1395 401). PMID- 26802714 TI - Reply. PMID- 26802715 TI - Reply. PMID- 26802716 TI - Re: Yamamoto et al.: One-year results of intravitreal aflibercept for polypoidal choroidal vasculopathy (Ophthalmology 2015;122:1866-72). PMID- 26802717 TI - Re: Berg et al.: Comparison of ranibizumab and bevacizumab for neovascular age related macular degeneration according to LUCAS treat-and-extend protocol (Ophthalmology 2015;122:146-52). PMID- 26802718 TI - Reply. PMID- 26802719 TI - Re: Ikuno et al.: Intravitreal aflibercept injection in patients with myopic choroidal neovascularization: the MYRROR study (Ophthalmology 2015;122:1220-7). PMID- 26802720 TI - Reply. PMID- 26802721 TI - Paved with good intentions: Paradoxical eating responses to weight stigma. AB - Because body weight is largely seen as controllable, weight stigma-the social devaluation of those who are overweight-is not subject to the social norms that condemn open expression of racism and sexism. Indeed, rejection of peers based on perceptions of excess weight is normative. Since weight stigma is internalized, popular views (and often the views of physicians) have suggested that increasing the salience of weight stigma might produce a reduction in overeating and/or an increase in physical activity. However, that perspective is not rooted in scientific evidence. Recent randomized controlled designs demonstrate that stigma may promote overeating. Correlational evidence suggests that self-reported stigma experience is associated with risk for binge eating and decreased interest in physical exercise and dieting, for children and adults. In addition to reviewing these research studies, this paper examines the potential for intersectionality of stigma across multiple social identities and considers alternatives to stigmatizing weight loss interventions. PMID- 26802722 TI - Systemic sclerosis: An update in 2016. AB - Systemic sclerosis (SSc) is a chronic immune disorder of unknown origin, dominated by excessive fibrosis responsible for cutaneous and pulmonary fibrosis, and by vascular endothelial dysfunction at the origin of skin ischemia, renal and pulmonary artery lesions. Renal and pulmonary complications are mainly responsible for the severity of the disease. Recent advances led to a better understanding of pathological mechanisms and a more accurate classification of patients according to clinical and biological (auto-antibodies) phenotype. Recent trials provided interesting data on different therapeutic strategies, depending on organ involvement. These data are of particular importance in such disease, still characterized by increased mortality and morbidity rates. In this review, we aim to synthetize recent advances in diagnosis and prognosis leading to better classification of SSc patients, and in therapeutic management. PMID- 26802723 TI - Functional organization of telencephalic visual association fields in pigeons. AB - Birds show remarkable visual abilities that surpass most of our visual psychophysiological abilities. In this study, we investigated visual associative areas of the tectofugal visual system in pigeons. Similar to the condition in mammals, ascending visual pathways in birds are subdivided into parallel form/color vs. motion streams at the thalamic and primary telencephalic level. However, we know practically nothing about the functional organization of those telencephalic areas that receive input from the primary visual telencephalic fields. The current study therefore had two objectives: first, to reveal whether these visual associative areas of the tectofugal system are activated during visual discrimination tasks; second, to test whether separated form/color vs. motion pathways can be discerned among these association fields. To this end, we trained pigeons to discriminate either form/color or motion stimuli and used the immediate early gene protein ZENK to capture the activity of the visual associative areas during the task. We could indeed identify several visual associative telencephalic structures by activity pattern changes during discriminations. However, none of these areas displayed a difference between form/color vs. motion sessions. The presence of such a distinction in thalamo telencephalic, but not in further downstream visual association areas opens the possibility that these separate streams converge very early in birds, which possibly minimizes long-range connections due to the evolutionary pressure toward miniaturized brains. PMID- 26802724 TI - Delayed administration IL-1beta neutralizing antibody improves cognitive function after transient global ischemia in rats. AB - In order to study the protective effects on motor and cognitive function by inhibiting IL-1beta as delayed as 24h after global ischemia, we designed behavioral testing protocol and histology detection after 10 min transient global ischemia followed by IL-1beta or its antibody intracerebroventricular injection. We found benefit of IL-1beta antibody treatment 24h after ischemia in cognitive function recovery. But no obvious amelioration in motor function was found. Further we detected cell morphology and survival by histology staining and proved IL-1beta antibody could reduce ischemia induced cell morphological changes and cell loss in hippocampus, which related with cognitive function. Present results indicate intervening IL-1beta pathway could be helpful in cognitive function recovery even as late as 24h after ischemia happens. PMID- 26802725 TI - Behavioral and monoamine perturbations in adult male mice with chronic inflammation induced by repeated peripheral lipopolysaccharide administration. AB - Considering the limited information on the ability of chronic peripheral inflammation to induce behavioral alterations, including on their persistence after inflammatory stimuli termination and on associated neurochemical perturbations, this study assessed the effects of chronic (0.25 mg/kg; i.p.; twice weekly) lipopolysaccharide (LPS) treatment on selected behavioral, neurochemical and molecular measures at different time points in adult male C57BL/6 mice. Behaviorally, LPS-treated mice were hypoactive after 6 weeks, whereas significant hyperactivity was observed after 12 weeks of LPS and 11 weeks after 13 week LPS treatment termination. Similar biphasic responses, i.e., early decrease followed by a delayed increase were observed in the open field test center time, suggestive of, respectively, increased and decreased anxiety. In a forced swim test, mice exhibited increased immobility (depressive behavior) at all times they were tested. Chronic LPS also produced persistent increase in splenic serotonin (5-HT) and time-dependent, brain region-specific alterations in striatal and prefrontocortical dopamine and 5-HT homeostasis. Microglia, but not astrocytes, were activated by LPS early and late, but their activation did not persist after LPS treatment termination. Above findings demonstrate that chronic peripheral inflammation initially causes hypoactivity and increased anxiety, followed by persistent hyperactivity and decreased anxiety. Notably, chronic LPS induced depressive behavior appears early, persists long after LPS termination, and is associated with increased splenic 5-HT. Collectively, our data highlight the need for a greater focus on the peripheral/central monoamine alterations and lasting behavioral deficits induced by chronic peripheral inflammation as there are many pathological conditions where inflammation of a chronic nature is a hallmark feature. PMID- 26802726 TI - Mutations in the circadian gene period alter behavioral and biochemical responses to ethanol in Drosophila. AB - Clock genes, such as period, which maintain an organism's circadian rhythm, can have profound effects on metabolic activity, including ethanol metabolism. In turn, ethanol exposure has been shown in Drosophila and mammals to cause disruptions of the circadian rhythm. Previous studies from our labs have shown that larval ethanol exposure disrupted the free-running period and period expression of Drosophila. In addition, a recent study has shown that arrhythmic flies show no tolerance to ethanol exposure. As such, Drosophila period mutants, which have either a shorter than wild-type free-running period (perS) or a longer one (perL), may also exhibit altered responses to ethanol due to their intrinsic circadian differences. In this study, we tested the initial sensitivity and tolerance of ethanol exposure on Canton-S, perS, and perL, and then measured their Alcohol Dehydrogenase (ADH) and body ethanol levels. We showed that perL flies had slower sedation rate, longer recovery from ethanol sedation, and generated higher tolerance for sedation upon repeated ethanol exposure compared to Canton-S wild-type flies. Furthermore, perL flies had lower ADH activity and had a slower ethanol clearance compared to wild-type flies. The findings of this study suggest that period mutations influence ethanol induced behavior and ethanol metabolism in Drosophila and that flies with longer circadian periods are more sensitive to ethanol exposure. PMID- 26802727 TI - The infralimbic and prelimbic medial prefrontal cortices have differential functions in the expression of anxiety-like behaviors in mice. AB - The medial prefrontal cortex is a heterogeneous cortical structure composed of several nuclei, including the prelimbic (PL) and infralimbic (IL) cortices. We previously demonstrated in mice that PL activation with the sodium channel activator veratrine induces anxiety-like behaviors. However, the role of IL in the regulation of anxiety-like behaviors remained unclear. Therefore, in the present study, we investigated the role of the IL in the regulation of anxiety like behaviors using pharmacological activation model with veratrine, and compared it with the role of the PL. Extracellular glutamate levels were measured by in vivo microdialysis-HPLC with an electrochemical detector, and behaviors were assessed using the open field test. In this study, extracellular glutamate levels rose significantly after perfusion of veratrine in the IL and PL. Interestingly, the PL activation produced anxiety-like behaviors, whereas the activation of the IL produced no anxiety-like behavior in mice. Although the IL is adjacent to the PL, these two regions of the brain have differential functions in the expression of anxiety-like behaviors. PMID- 26802728 TI - The antagonism of ghrelin alters the appetitive response to learned cues associated with food. AB - The rapid increase in obesity may be partly mediated by an increase in the exposure to cues for food. Food-paired cues play a role in food procurement and intake under conditions of satiety. The mechanism by which this occurs requires characterization, but may involve ghrelin. This orexigenic peptide alters the response to food-paired conditioned stimuli, and neural responses to food images in reward nuclei. Therefore, we tested whether a ghrelin receptor antagonist alters the influence of food-paired cues on the performance of instrumental responses that earn food and the consumption of food itself using tests of Pavlovian-to-instrumental transfer (PIT) and cue potentiated feeding (CPF), respectively. Food-deprived rats received Pavlovian conditioning where an auditory cue was paired with delivery of sucrose solution followed by instrumental conditioning to lever press for sucrose. Following training, rats were given ad libitum access to chow. On test day, rats were injected with the ghrelin receptor antagonist GHRP-6 [D-Lys3] and then tested for PIT or CPF. Disrupting ghrelin signaling enhanced expression of PIT. In addition, GHRP-6 [D Lys3] impaired the initiation of feeding behavior in CPF without influencing overall intake of sucrose. Finally, in PIT tested rats, enhanced FOS immunoreactivity was revealed following the antagonist in regions thought to underlie PIT; however, the antagonist had no effect on FOS immunoreactivity in CPF tested rats. PMID- 26802729 TI - Stop or move: Defensive strategies in humans. AB - Threatening cues and surrounding contexts trigger specific defensive response patterns. Potential threat evokes attentive immobility; attack evokes flight when escape is available and immobility when escape is blocked. Tonic immobility installs when threat is overwhelming and life-risky. In humans, reduced body sway characterizes attentive and tonic immobility, the former with bradycardia, and the later with expressive tachycardia. Here, we investigate human defensive strategies in the presence or absence of an escape route. We employed pictures depicting a man carrying a gun and worked with participants exposed to urban violence. In pictures simulating more possibility of escape, the gun was directed away from the observer; in those simulating higher risk and less chance of escape, the gun was directed toward the observer. Matched control pictures depicted similar layouts, but a non-lethal object substituted the gun. Posturographic and electrocardiographic recordings were collected. Amplitude of sway and heart rate were higher for gun directed-away and lower for gun direct toward. Compared to their respective matched controls, there was a general increase in the amplitude of sway for the gun directed-away pictures; and a reduction in back-and-forth sway and in heart rate for gun directed-toward pictures. Taken together, those measures suggest that, when exposed to threat invading their margin of safety in a context indicating possible escape route, humans, as non-human species, engage in active escape, resembling the flight stage of the defensive cascade. When facing threat indicating less possibility of escape, humans present an immobile response with bradycardia. PMID- 26802730 TI - Alcohol enhances unprovoked 22-28 kHz USVs and suppresses USV mean frequency in High Alcohol Drinking (HAD-1) male rats. AB - Heightened emotional states increase impulsive behaviors such as excessive ethanol consumption in humans. Though positive and negative affective states in rodents can be monitored in real-time through ultrasonic vocalization (USV) emissions, few animal studies have focused on the role of emotional status as a stimulus for initial ethanol drinking. Our laboratory has recently developed reliable, high-speed analysis techniques to compile USV data during multiple-hour drinking sessions. Since High Alcohol Drinking (HAD-1) rats are selectively bred to voluntarily consume intoxicating levels of alcohol, we hypothesized that USVs emitted by HAD-1 rats would reveal unique emotional phenotypes predictive of alcohol intake and sensitive to alcohol experience. In this study, male HAD-1 rats had access to water, 15% and 30% EtOH or water only (i.e., Controls) during 8 weeks of daily 7-h drinking-in-the-dark (DID) sessions. USVs, associated with both positive (i.e., 50-55 kHz frequency-modulated or FM) and negative (i.e., 22 28 kHz) emotional states, emitted during these daily DID sessions were examined. Findings showed basal 22-28 kHz USVs were emitted by both EtOH-Naive (Control) and EtOH-experienced rats, alcohol experience enhanced 22-28 kHz USV emissions, and USV acoustic parameters (i.e., mean frequency in kHz) of both positive and negative USVs were significantly suppressed by chronic alcohol experience. These data suggest that negative affective status initiates and maintains excessive alcohol intake in selectively bred HAD-1 rats and support the notion that unprovoked emissions of negative affect-associated USVs (i.e., 22-28 kHz) predict vulnerability to excessive alcohol intake in distinct rodent models. PMID- 26802733 TI - Continuity and innovation. PMID- 26802731 TI - A species-specific activation of Toll-like receptor signaling in bovine and sheep bronchial epithelial cells triggered by Mycobacterial infections. AB - Pulmonary tuberculosis caused by a Mycobacterium infection remains a major public health problem in most part of the world, in part owing to the transmission of its pathogens between hosts including human, domestic and wild animals. To date, molecular mechanisms of the pathogenesis of TB are still incompletely understood. In addition to alveolar macrophages, airway epithelial cells have also been recently recognized as main targets for Mycobacteria infections. In an effort to understand the pathogen-host interaction between Mycobacteria and airway epithelial cells in domestic animals, in present study, we investigated the Toll like receptor (TLR) signaling in bovine and sheep airway epithelial cells in response to an infection of Mycobacterium tuberculosis avirulent H37Ra stain or Mycobacterium bovis BCG vaccine strain, using primary air-liquid interface (ALI) bronchial epithelial culture models. Our results revealed a host and pathogen species-specific TLR-mediated recognition of pathogen-associated molecular patterns (PAMPs), induction and activation of TLR signaling pathways, and substantial induction of inflammatory response in bronchial epithelial cells in response to Mycobacteria infections between these two species. Interestingly, the activation TLR signaling in bovine bronchial epithelial cells induced by Mycobacteria infection was mainly through a myeloid differentiation factor 88 (MyD88)-independent TLR signaling pathway, while both MyD88-dependent and independent TLR signaling cascades could be induced in sheep epithelial cells. Equally noteworthy, a BCG infection was able to induce both MyD88-dependent and independent signaling in sheep and bovine airway epithelial cells, but more robust inflammatory responses were induced in sheep epithelial cells relative to the bovines; whereas an H37Ra infection displayed an ability to mainly trigger a MyD88-independent TLR signaling cascade in these two host species, and induce a more extent expression of inflammatory cytokines in bovine cells in comparison with that in sheep. These data thus provide an evidence for a host and pathogen species-specific response in bovine and sheep airway epithelial cells in response to Mycobacteria infections, which also suggest there is a need to consider in the interpretation of data generated using a species other than the primary host for analysis of a function role or mechanism of ligands or pathogens. PMID- 26802732 TI - A fluorescent method for visualization of Nosema infection in whole-mount honey bee tissues. AB - Honey bees are critical pollinators in both agricultural and ecological settings. The Nosema species, ceranae and apis, are microsporidian parasites that are pathogenic to honey bees. While current methods for detecting Nosema infection have key merits, additional techniques with novel properties for studying the cell biology of Nosema infection are highly desirable. We demonstrate that whole mount staining of honey bee midgut tissue with chitin-binding agent Fluorescent Brightener 28 and DNA dye Propidium Iodide allows for observation of Nosema infection in structurally intact tissue, providing a new tool for increasing our understanding of Nosema infection at the cellular and tissue level. PMID- 26802734 TI - AISF-SIMTI Position Paper: The appropriate use of albumin in patients with liver cirrhosis. AB - The use of human albumin is common in hepatology since international scientific societies support its administration to treat or prevent severe complications of cirrhosis, such as the prevention of post-paracentesis circulatory dysfunction after large-volume paracentesis and renal failure induced by spontaneous bacterial peritonitis, and the treatment of hepatorenal syndrome in association with vasoconstrictors. However, these indications are often disregarded, mainly because the high cost of human albumin leads health authorities and hospital administrations to restrict its use. On the other hand, physicians often prescribe human albumin in patients with advanced cirrhosis for indications that are not supported by solid scientific evidence and/or are still under investigation in clinical trials. In order to implement appropriate prescription of human albumin and to avoid its futile use, the Italian Association for the Study of the Liver (AISF) and the Italian Society of Transfusion Medicine and Immunohaematology (SIMTI) nominated a panel of experts, who reviewed the available clinical literature and produced practical clinical recommendations for the use of human albumin in patients with cirrhosis. PMID- 26802735 TI - Prolonged hypothermia exposure diminishes neuroprotection for severe ischemic hypoxic primary neurons. AB - This study aimed to identify optimal mild hypothermic (MH) condition that would provide the best protection for neuronal cells undergoing severe ischemia and hypoxia. We also sought to determine if longer exposure to mild hypothermia would confer greater protection to severe ischemia and hypoxia in these cells. We designed a primary neuronal cell model for severe glucose and oxygen deprivation/reoxygenation (OGD/R) to simulate the hypoxic-ischemic condition of patients with severe stroke, trauma, or hypoxic-ischemic encephalopathy. We evaluated the viability of these neurons following 3 h of OGD/R and variable MH conditions including different temperatures and durations of OGD/R exposure. We further explored the effects of the optimal MH condition on several parts which are associated with mitochondrial apoptosis pathway: intracellular calcium, reactive oxygen species (ROS), and mitochondrial transmembrane potential (MTP). The results of this study showed that the apoptosis proportion (AP) and cell viability proportion (CVP) after OGD/R significantly varied depending on which MH condition cells were exposed to (p < 0.001). Further, our findings showed that prolonged MH reduced the neuroprotection to AP and CVP. We also determined that the optimal MH conditions (34 degrees C for 4.5 h) reduced intracellular calcium, ROS, and recovered MTP. These findings indicate that there is an optimal MH treatment strategy for severely hypoxia-ischemic neurons, prolonged duration might diminish the neuroprotection, and that MH treatment likely initiates neuroprotection by inhibiting the mitochondrial apoptosis pathway. PMID- 26802737 TI - Reply by Authors. PMID- 26802736 TI - A comparison of activity patterns for captive Propithecus tattersalli and Propithecus coquereli. AB - The activity patterns and social interactions of two species of captive sifaka were observed during a 2-year period. Allogrooming was not observed in golden crowned sifaka and they spent significantly more time resting than the Coquerel's sifaka. Females of both species were found to be dominant to males. The golden crowned sifaka (Propithecus tattersalli) spent significantly less time feeding than the Coquerel's sifaka. Temperature, time of day, species, and interpair comparisons for the golden-crowned sifaka were found to affect activity and social interactions, while gender did not. Like the Coquerel's sifaka, the golden crowned sifaka was found to be diurnal; however, they differed in that the golden crowned sifaka did not descend to the ground. PMID- 26802738 TI - Editorial Comment. PMID- 26802739 TI - Editorial Comment. PMID- 26802740 TI - Editorial Comment. PMID- 26802741 TI - Oestrogen activity of the serum in adolescents with Type 1 diabetes. AB - AIMS: To assess serum oestrogen levels and oestrogenic activity in adolescents with Type 1 diabetes compared with a healthy control group. METHODS: We conducted a cross-sectional study that evaluated adolescents with Type 1 diabetes (n = 38) and healthy adolescents (control group; n = 32). Serum oestrogens, urinary oestrogen metabolites and serum oestrogenic activity were assessed. Oestrogenic activity was evaluated in an in vitro cell proliferation assay using a modified E screen assay with MCF-7/BUS cells. RESULTS: Adolescents with Type 1 diabetes had lower oestrogenic activity levels in both phases of the menstrual cycle compared with the control group (follicular phase: 76 vs 94%; luteal phase: 97 vs 131%; P < 0.01), even after adjusting for BMI, oestradiol and oestrone levels. Postmenarcheal adolescents with Type 1 diabetes had lower oestradiol levels compared with control subjects in the follicular phase (63.3 pmol/l vs 89.4 pmol/l; P < 0.01) and higher oestrone levels compared with controls in the luteal phase (196 vs 151.9 pmol/l; P < 0.05). CONCLUSIONS: Adolescents with Type 1 diabetes had lower levels of serum oestrogenic activity, and these were lower than expected based on their serum oestradiol levels. We postulate that changes in the serum milieu of oestrogens in patients with Type 1 diabetes may explain their decreased oestrogenic activity and may play a role in their adverse metabolic profile. PMID- 26802742 TI - Physicochemical and biological characterizations of Pxt peptides from amphibian (Xenopus tropicalis) skin. AB - Pxt peptides (Pxt-1 through Pxt-12) have been isolated from amphibian, Xenopus tropicalis Pxt-related peptides (Pxt-2, Pxt-5, Pxt-12, reverse Pxt-2, reverse Pxt 5 and reverse Pxt-12) with significant foaming properties were further characterized. In the physicochemical experiments, all Pxt-related peptides formed significant amphiphilic alpha-helices in 50% 2,2,2-trifluoroethanol by circular dichroism measurements. Among Pxt-related peptides, both Pxt-5 and reverse Pxt-5 were the most effective in reducing their surface tensions. Moreover, Pxt-2, Pxt-5 and reverse Pxt-5 produced constant surface tensions above their critical association concentrations, suggesting the micelle-like assemblies. In the biological experiments, Pxt-5 possessed the most potent hemolytic activity, while reverse Pxt-5 exhibited the most remarkable gene expression of interleukin 8 and heme oxygenase 1 and the most potent cytotoxicity in HaCaT cells. In contrast, Pxt-12 and reverse Pxt-12 were much weaker in antimicrobial assays for Gram-negative bacteria, Gram-positive bacteria and yeasts, as well as in hemolytic, cell viability and cytotoxicity assays in HaCaT cells. All Pxt-related peptides exhibited about 20-50% of the total cellular histamine release at 10(-5) M, as well as mastoparan and melittin in mast cells. Real-time polymerase chain reaction analysis confirmed the gene expressions of Pxt-5 in testis and Pxt-12 in muscle, in addition to skin, while Pxt-2 was only in skin. PMID- 26802743 TI - KIAA0368-deficiency affects disassembly of 26S proteasome under oxidative stress condition. AB - Many cellular stresses cause damages of intracellular proteins, which are eventually degraded by the ubiquitin and proteasome system. The proteasome is a multicatalytic protease complex composed of 20S core particle and the proteasome activators that regulate the proteasome activity. Extracellular mutants 29 (Ecm29) is a 200 kDa protein encoded by KIAA0368 gene, associates with the proteasome, but its role is largely unknown. Here, we generated KIAA0368 deficient mice and investigated the function of Ecm29 in stress response. KIAA0368-deficient mice showed normal peptidase activity and proteasome formation at normal condition. Under stressed condition, 26S proteasome dissociates in wild type cells, but not in KIAA0368(-/-) cells. This response was correlated with efficient degradation of damaged proteins and resistance to oxidative stress of KIAA0368(-/-) cells. Thus, Ecm29 is involved in the dissociation process of 26S proteasome, providing clue to analyse the mechanism of proteasomal degradation under various stress condition. PMID- 26802744 TI - Use of noise in gene expression as an experimental parameter to test phenotypic effects. AB - During the last decade, the molecular basis for gene expression noise has been mostly deciphered, helping understanding of how gene regulation is controlled and how the generation of cell-cell non-genetic heterogeneity is modulated through noise. In the same period, the functional importance of phenotypic heterogeneity among cell populations has been recognized and widely involved in major biological phenomena. Surprisingly, only a few studies connect these two highly active research fields, most of them having been obtained using the yeast Saccharomyces cerevisiae. This organism has long been the preferred model for studying many aspects of gene expression noise, especially revealing that evolution seems to act to either increase or decrease gene expression noise, depending on whether the associated phenotypic heterogeneity is beneficial or deleterious to the population. Nevertheless, direct evidences of phenotypic consequences of noise differences are often lacking, in spite of this evolutionary tendency. This rarity is probably due to the complex relationships between mean and noise levels, making the study of the sole effect of noise difficult, and also to problems caused by the detection of cell-cell expression variability of native functional proteins, allowing the testing of specific phenotypic effects. Despite these difficulties, the widespread use of gene expression noise as an experimental parameter at equal mean expression levels to test phenotypic consequences would often help to change explanations of cell population behaviour beyond the simple consideration of average expression levels, and constitute a major step towards single-cell biology. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26802745 TI - Expression of c-Fos protein in medial septum/diagonal band of Broca and CA3 region, associated with the temporary inactivation of the supramammillary area. AB - The supramammillary (SuM) area is part of the diencephalic nuclei comprising the mammillary bodies, and is a key structure in the memory and spatial learning processes. It is a critical region in the modulation/generation of hippocampal theta rhythm. In addition, many papers have recently shown a clear involvement of this structure in the processes of spatial learning and memory in animal models, although it is still not known how it modulates spatial navigation and response emotional. The aim of the present research was to study the effect of the temporary inactivation of the SuM area on synaptic plasticity of crucial structures in the formation of spatial memory and emotional response. Sprague Dawley rats were asigned in three groups: a control group where the animals were not subjected to any treatment, and two groups where the rats received microinjections of tetrodotoxin (TTX) in the SuM area (5ng diluted in 0.5MUl of saline) or saline (0.5MUl). The microinjections were administered 90min before the perfusion. Later, cellular activity in medial septum/diagonal band of Broca (MS/DBB) and CA3 region of the dorsal hippocampus was assessed, by measuring the immediate early gene c-fos. The results show a clear hiperactivity cellular in medial septum/diagonal band of Broca and a clear hypoactivity cellular in the CA3 region of the hippocampus when there was a functional inactivation of the SuM area. It suggests that the SuM area seems to be part of the connection and information input pathways to CA3 region of the hippocampal formation, key for proper functioning in spatial memory and emotional response. PMID- 26802746 TI - Evolution of DNA aptamers for malignant brain tumor gliosarcoma cell recognition and clinical tissue imaging. AB - Gliosarcoma, a variant of glioblastoma multiforme (GBM), is a highly invasive malignant tumor. Unfortunately, this disease still marked by poor prognosis regardless of modern treatments. It is of great significance to discover specific molecular probes targeting gliosarcoma for early cancer diagnosis and therapy. Herein, we have selected a group of DNA aptamers with high affinity and selectivity against gliosarcoma cells K308 using cell-SELEX. All the dissociation constants of these aptamers against gliosarcoma cells were in the nanomolar range and aptamer WQY-9 has the highest affinity and good selectivity among them. Furthermore, truncated aptamer sequence, WQY-9-B, shows similar recognition ability to aptamer WQY-9. In addition, WQY-9-B was found to be able to bind selectively and internalize into cytoplasm of target cancer cell at 37 degrees C. More importantly, compared to a random sequence, aptamer WQY-9-B showed excellent recognition rate (73.3%) for tissue sections of clinical gliosarcoma samples. These data suggests that aptamer WQY-9-B has excellent potential as an effective molecular probe for gliosarcoma diagnosis. PMID- 26802748 TI - An aldehyde group-based P-acid probe for selective fluorescence turn-on sensing of cysteine and homocysteine. AB - A highly sensitive and selective turn on fluorescent probe P-acid-aldehyde (P CHO) is developed for the determination of cysteine (Cys) and homocysteine (Hcy). The probe is designed and synthesized by incorporating the specific functional group aldehyde group for thiols into a stable pi-conjugated material 4,4'-(2,5 dimethoxy-1,4-phenylene) bis(ethyne-2,1-diyl) dibenzoic acid (P-acid). The probe fluorescence is quenched through donor photoinduced electron transfer (d-PET) between the fluorophore (P-acid) and the recognition group (aldehyde group). In the presence of thiols, Cys and Hcy can selectively react with aldehyde group of the probe because the inhibition of d-PET between fluorophore and recognition group. Therefore, a turn-on fluorescent sensor was established for the fluorescence recovery. Under the optimized conditions, the fluorescence response of probe is directly proportional to the concentration of Cys in the range of 4 95 NM L(-1), with a detection limit 3.0 nM. In addition, the sensing system exhibits good selectively toward Cys and Hcy in the presence of other amino acids. It has been successfully applied for bioimaging of Cys and Hcy in living cells with low cell toxicity. PMID- 26802747 TI - Biosensors based on modularly designed synthetic peptides for recognition, detection and live/dead differentiation of pathogenic bacteria. AB - Rapid and sensitive detection of bacterial pathogens is critical for assessing public health, food and environmental safety. We report the use of modularly designed and site-specifically oriented synthetic antimicrobial peptides (sAMPs) as novel recognition agents enabling detection and quantification of bacterial pathogens. The oriented assembly of the synthetic peptides on electrode surfaces through an engineered cysteine residue coupled with impedimetric detection facilitated rapid and sensitive detection of bacterial pathogens with a detection limit of 10(2)CFU/mL for four bacterial strains including Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis). The approach enabled differentiation between live and dead bacteria. The fabrication of the sAMPs functionalized surface and the importance of the sAMPs orientation for providing optimum recognition and detection ability against pathogens are discussed. The proposed methodology provides a universal platform for the detection of bacterial pathogens based on engineered peptides, as alternative to the most commonly used immunological and gene based assays. The method can also be used to fabricate antimicrobial coatings and surfaces for inactivation and screening of viable bacteria. PMID- 26802749 TI - Electrochemical magnetic microbeads-based biosensor for point-of-care serodiagnosis of infectious diseases. AB - Access to appropriate diagnostic tools is an essential component in the evaluation and improvement of global health. Additionally, timely detection of infectious agents is critical in early diagnosis and treatment of infectious diseases. Conventional pathogen detection methods such as culturing, enzyme linked immunosorbent assay (ELISA) or polymerase chain reaction (PCR) require long assay times, and complex and expensive instruments making them not adaptable to point-of-care (PoC) needs at resource-constrained places and primary care settings. Therefore, there is an unmet need to develop portable, simple, rapid, and accurate methods for PoC detection of infections. Here, we present the development and validation of a portable, robust and inexpensive electrochemical magnetic microbeads-based biosensor (EMBIA) platform for PoC serodiagnosis of infectious diseases caused by different types of microorganisms (parasitic protozoa, bacteria and viruses). We demonstrate the potential use of the EMBIA platform for in situ diagnosis of human (Chagas disease and human brucellosis) and animal (bovine brucellosis and foot-and-mouth disease) infections clearly differentiating infected from non-infected individuals or animals. For Chagas disease, a more extensive validation of the test was performed showing that the EMBIA platform displayed an excellent diagnostic performance almost indistinguishable, in terms of specificity and sensitivity, from a fluorescent immunomagnetic assay and the conventional ELISA using the same combination of antigens. This platform technology could potentially be applicable to diagnose other infectious and non-infectious diseases as well as detection and/or quantification of biomarkers at the POC and primary care settings. PMID- 26802750 TI - Supercritical carbon dioxide-assisted rapid synthesis of few-layer black phosphorus for hydrogen peroxide sensing. AB - Solutions with large-scale dispersions of 2D black phosphorus (BP), often referred to as phosphorene, are obtained through solvent exfoliation. But, rapid phosphorene synthesis remains a challenge. Furthermore, although the chemical sensing capability of BP-based sensors has been theoretically predicted, its experimental verification remains lacking. In this study, we demonstrate the use of supercritical carbon dioxide-assisted rapid synthesis (5h) of few-layer BP. In addition, we construct a non-enzymatic hydrogen peroxide (H2O2) sensor based on few-layer BP for the first time to utilize BP degradation under ambient conditions. The proposed H2O2 sensor exhibits a considerably lower detection limit of 1 * 10(-7) M compared with the general detection limit of 1 * 10(-7) M-5 * 10(-5)M via electrochemical methods. Overall, the results of this study will not only expand the coverage of BP research but will also identify the important sensing characteristics of BP. PMID- 26802751 TI - "To Improve Is to Change": Improving U.S. Healthcare. PMID- 26802752 TI - Change, Challenge and Opportunity: Departments of Medicine and Their Leaders. AB - Academic Health Centers are evolving to larger and more complex Academic Health Systems (AHS), reflecting financial stresses requiring them to become nimble, efficient, and patient (consumer) and faculty (employee) focused. The evolving AHS organization includes many positive attributes: unity of purpose, structural integration, collaboration and teamwork, alignment of goals with resource allocation, and increased financial success. The organization, leadership, and business acumen of the AHS influence directly opportunities for Departments of Medicine. Just as leadership capabilities of the AHS affect its future success, the same is true for departmental leadership. The Department of Medicine is no longer a quasi- autonomous entity, and the chairperson is no longer an independent decision-maker. Departments of Medicine will be most successful if they maintain internal unity and cohesion by not fragmenting along specialty lines. Departments with larger endowments or those with public financial support have more flexibility when investing in the academic missions. The chairpersons of the future should serve as change agents while simultaneously adopting a "servant leadership" model. Chairpersons with executive and team building skills, and business acumen and experience, are more likely to succeed in managing productive and lean departments. Quality of patient care and service delivery enhance the department's effectiveness and credibility and assure access to additional financial resources to subsidize the academic missions. Moreover, the drive for excellence, high performance and growth will fuel financial solvency. PMID- 26802753 TI - The Nation's Physician Workforce and Future Challenges. AB - There is much debate about the adequacy of the U.S. physician workforce and projections of its future size, distribution and composition. Beginning with 3 observations about the workforce we believe are largely not subject to dispute, we address the debate by providing an overview of the current state of the workforce and Graduate Medical Education in the United States; a brief history of both calls for graduate medical education reform since 1910 and the recent, intense debate about the reliability of workforce projections; and a discussion of the challenges to understanding the physician workforce. We draw 3 concluding observations: (1) Precisely because projections can be unpredictable in their impact on both physician workforce behavior and public policy development, policy makers need to devote more attention to workforce projections, not less. (2) More research devoted specifically to the workforce implications of delivery and payment reforms is strongly needed. (3) Such research must be pursued with a sense of urgency, given the rapid aging of the Baby Boom generation, which will put a disproportionate demand on the nation's physician workforce. PMID- 26802754 TI - Primary Care: Medicine's Gordian Knot. AB - Primary care is the cornerstone of effective and efficient healthcare systems. Patients prefer a trusted primary care provider to serve as the first contact for all of their healthcare questions, to help them make important health decisions, to help guide them through an expanding amount of medical information and to help coordinate their care with all other providers. Patients also prefer to establish an ongoing, continuous relationship with their primary care provider. However, fewer and fewer physicians are choosing primary care as a career, threatening the foundation of the health system. We explore the central challenges of primary care defined by work-force controversies about who can best deliver primary care. We also explore the current challenging reimbursement model for primary care that often results in fragmenting care for patients and providers. Finally, we explore new models of primary care health delivery that may serve as partial solutions to the current challenges. PMID- 26802755 TI - Population Health: A New Paradigm for Medicine. AB - Healthcare delivery system reform has become a dominant topic of conversation throughout the United States. Driven in part by ever-higher national expenditures on health, an increasing number of payers and provider organizations are working to reduce the costs and improve the quality of healthcare. In this article, we demystify the term "Population Health," review some of the larger payer initiatives currently in effect and discuss specific provider group efforts to improve the quality and cost of healthcare for patients. PMID- 26802757 TI - The Value Equation: Enhancing Patient Outcomes While Constraining Costs. PMID- 26802756 TI - Achieving Equity in an Evolving Healthcare System: Opportunities and Challenges. AB - For decades, disparities in health have been well documented in the United States and regrettably, remain prevalent despite evidence and appeals for their elimination. Compared with the majority, racial and ethnic minorities continue to have poorer health status and health outcomes for most chronic conditions, including diabetes mellitus, cardiovascular disease, cancer and end-stage renal disease. Many factors, such as affordability, access and diversity in the healthcare system, influence care and outcomes, creating challenges that make the task of eliminating health disparities and achieving health equity daunting and elusive. Novel strategies are needed to bring about much needed change in the complex and evolving United States healthcare system. Although not exhaustive, opportunities such as (1) developing standardized race measurements across health systems, (2) implementing effective interventions, (3) improving workforce diversity, (4) using technological advances and (5) adopting practices such as personalized medicine may serve as appropriate starting points for moving toward health equity. Over the past several decades, diversity in the U.S. population has increased significantly and is expected to increase exponentially in the near future. As the population becomes more diverse, it is important to recognize the possibilities of new and emerging disparities. It is imperative that steps are taken to eliminate the current gap in care and prevent new disparities from developing. Therefore, we present challenges and offer recommendations for facilitating the process of eliminating health disparities and achieving health equity across diverse populations. PMID- 26802758 TI - The Role of Government in Physician Reimbursement. AB - BACKGROUND: Governments around the world exert a substantial degree of influence over physician reimbursement, but the structure and level of that influence varies greatly. This article defines and analyzes the role of government in physician reimbursement both internationally and in the United States. ANALYTICAL FRAMEWORK: We create a typology for government involvement in physician reimbursement that divides intervention into either direct control or indirect control. Within those broad categories, we describe more specific forms of involvement including rate setting, operating as a public payer, employing physicians directly, providing a source of market discipline, regulating private insurance, and convening private participants in the market. FINDINGS: We apply our framework to the modern healthcare systems of Germany, Sweden, Canada, and the United States, highlighting some of the implications of differences between the systems. Our central finding is that in contrast to other example healthcare systems, the United States system features a complex interplay of federal and state government influence, both direct and indirect, into physician reimbursement. CONCLUSION: We conclude the article by examining the ways in which recent legislation including the Affordable Care Act and the Medicare Access and CHIP Reauthorization Act would likely change the role of government in physician reimbursement in the United States. PMID- 26802759 TI - The Promise of Information and Communication Technology in Healthcare: Extracting Value From the Chaos. AB - Healthcare is an information business with expanding use of information and communication technologies (ICTs). Current ICT tools are immature, but a brighter future looms. We examine 7 areas of ICT in healthcare: electronic health records (EHRs), health information exchange (HIE), patient portals, telemedicine, social media, mobile devices and wearable sensors and monitors, and privacy and security. In each of these areas, we examine the current status and future promise, highlighting how each might reach its promise. Steps to better EHRs include a universal programming interface, universal patient identifiers, improved documentation and improved data analysis. HIEs require federal subsidies for sustainability and support from EHR vendors, targeting seamless sharing of EHR data. Patient portals must bring patients into the EHR with better design and training, greater provider engagement and leveraging HIEs. Telemedicine needs sustainable payment models, clear rules of engagement, quality measures and monitoring. Social media needs consensus on rules of engagement for providers, better data mining tools and approaches to counter disinformation. Mobile and wearable devices benefit from a universal programming interface, improved infrastructure, more rigorous research and integration with EHRs and HIEs. Laws for privacy and security need updating to match current technologies, and data stewards should share information on breaches and standardize best practices. ICT tools are evolving quickly in healthcare and require a rational and well-funded national agenda for development, use and assessment. PMID- 26802760 TI - The U.S. Public's Investment in Medical Research: An Evolving Social Contract. AB - Medical researchers and their institutions are operating under extraordinary financial stress. More than a decade after completion of the 5-year doubling of the National Institutes of Health budget, the medical research community must confront a significant loss in National Institutes of Health purchasing power and downward pressures in federal discretionary spending. In part, this trend results from a federal budget stalemate over the growth in entitlement programs, particularly spending on medical care. This article considers the changing nature of the federal investment in medical research and the potential for medical researchers and institutions conducting the full spectrum of research to improve health system performance and health equity. In our view, continued federal investments reflect an evolving social contract for research serving the public good; the term contract is used metaphorically to represent a figurative, implicit agreement between the scientific community and the public's representatives in government. Under this conceptual contract, the American people--who are ultimately the funders of research, research training and infrastructure--expect outcomes that lead to better health, security or other benefits. The evolving contract includes expectations for more accountability, transparency, sharing of results and resources, and better integration of research systems and cultures that used to take pride in boundaries and distinctions. We outline here some of the major movements of organizations realigning to social support, which are increasingly essential to sustain public investment in medical research. PMID- 26802761 TI - Redesigning Medical Education in Internal Medicine: Adapting to the Changing Landscape of 21st Century Medical Practice. PMID- 26802762 TI - Endoscopic Retrograde Cholangiopancreatography in the Elderly. AB - BACKGROUND: The use of gastrointestinal endoscopy in geriatric patients is rising as an increasing proportion of the population is reaching an advanced age. Most studies of endoscopic retrograde cholangiopancreatography (ERCP) in the elderly have been done in tertiary care or referral centers. METHODS: We analyzed the clinical and endoscopic data on all ERCPs in patients aged 65 years and older in a retrospective review of medical records of patients at the county hospitals in El Paso and Lubbock, Texas between 2004 and 2008. ERCP data in patients aged 75 years and older were compared with those who were 65-74 years. RESULTS: There were 125 ERCPs performed in 89 patients (74 procedures in 54 patients older than 75 years, 51 procedures in 35 patients younger than 75 years). The average age was 76.0 (range: 65-94), 62.4% were female and 79.2% were Hispanic. Indications were similar between groups: jaundice (66.9%), abnormal liver tests (87.2%), abdominal pain (79.2%), cholangitis (24.0%), pancreatitis (32.8%) and stent change (12.9%). Concomitant illnesses were also similar. Lower doses of midazolam and meperidine were used for moderate sedation in the older group (P < 0.01). ERCP findings were similar in both groups: stones (40.8%), stricture (18.4%) and stent placement (30.4%). Complications occurred in 6.4%. CONCLUSIONS: This study of ERCP in elderly predominantly Hispanic patients found similar indications, efficacy and safety in patients 75 years and older compared with those 65-74 years old. Advanced age is not a contraindication to ERCP, but issues related to sedation and the use of antithrombotic therapy need to be addressed in the elderly. PMID- 26802763 TI - Body Mass Index, Left Ventricular Mass Index and Cardiovascular Events in Chronic Kidney Disease. AB - BACKGROUND: Obesity and left ventricular hypertrophy are prevalent in chronic kidney disease (CKD), but the association of body mass index (BMI) and left ventricular mass index (LVMI) with cardiovascular outcomes in patients with CKD is unclear. This study was designed to assess whether the combination of BMI and LVMI is independently associated with cardiovascular events in patients with CKD stages 3-5. METHODS: From the outpatient department, 523 patients with CKD who received echocardiographic examination were enrolled. The patients under study were classified into 4 groups according to sex-specific median BMIs and LVMIs. Cardiovascular events were defined as cardiovascular death, hospitalization for unstable angina, nonfatal myocardial infarction, sustained ventricular arrhythmia, hospitalization for congestive heart failure, transient ischemia attack and stroke. The relative cardiovascular event risk was analyzed using Cox regression methods. RESULTS: The patients were stratified into 4 groups according to sex-specific median BMIs (men: 25.2 kg/m(2); women: 24.9 kg/m(2)) and LVMIs (men: 140.1g/m(2); women: 131.6g/m(2)). A combination of low BMI and high LVMI (versus the combination of high BMI and low LVMI) was significantly associated with cardiovascular events in an unadjusted model (hazard ratio [HR] = 3.178; 95% confidence interval [CI]: 1.645-6.140; P < 0.001) and in a multivariable model after adjustment for demographic, clinical and biochemical characteristics and medications (HR = 3.553; 95% CI: 1.494-8.450; P = 0.004). CONCLUSIONS: The findings showed that the combination of low BMI and high LVMI was associated with adverse cardiovascular events in patients with CKD stages 3-5. PMID- 26802764 TI - Comorbidities of Chronic Complete Right Bundle Branch Block and Correlations With Coronary Angiographic Findings. AB - BACKGROUND: This is a prospective, observational review of medical records to investigate the associated comorbidities and angiographic anatomy in patients with chronic right bundle branch block (RBBB). METHODS: The analyses of 32,345 consecutive electrocardiograms (EKGs) between October 2010 and January 2012 revealed 583 patients with RBBB. The common comorbidities associated with RBBB were hypertension (82%), diabetes (42%), coronary artery disease (CAD) (44%), valvular heart disease (aortic--16% and mitral--17%) and pulmonary disease (33%). Demographic data including age, sex, EKG and associated comorbidities were analyzed from the medical records. Coronary angiograms within 6 months of EKG in patients with RBBB were available for 184 patients and were accordingly analyzed for significant obstructive CAD. RESULTS: In all, 33 patients had single-vessel disease, 52 patients had 2-vessel disease, and 87 patients had multivessel disease whereas 12 patients had no significant disease. Left anterior descending artery was the most frequent vessel involved (72%) followed by left circumflex (58%) and right coronary artery (53%). CONCLUSIONS: In conclusion, in chronic RBBB, wherever the angiograms were available, CAD predominantly involved left anterior descending artery. Most common associated comorbidities in chronic RBBB were systemic hypertension and CAD. PMID- 26802765 TI - Clinical Profile and Prognosis of Left Ventricular Apical Aneurysm in Hypertrophic Cardiomyopathy. AB - BACKGROUND: Hypertrophic cardiomyopathy with left ventricular apical aneurysm is a unique entity with diverse manifestations and varied prognoses among races. This study evaluated the prevalence, clinical characteristics and outcomes of apical aneurysm in Chinese patients with hypertrophic cardiomyopathy. METHODS: Consecutive patients with apical aneurysm were recruited from 1,844 patients with HCM treated at our hospital from 2002-2013. Basic clinical data and follow-up data were collected and analyzed. RESULTS: Apical aneurysm was identified in 24 patients (1.3%) (mean age: 52 +/- 14 years). We identified an hourglass-shaped (71%) or distally hypertrophic (29%) left ventricle and found mural thrombi and nonsustained and sustained ventricular tachycardia in 11 (46%), 4 (17%) and 9 (38%) patients, respectively. During follow-up (5.0 +/- 3.4 years [range: 1-14 years]), following were the clinical adverse events experienced by 14 patients (58%) (annual rate: 11.7%): sudden cardiac death (n = 4), appropriate discharge of an implantable cardioverter-defibrillator (n = 4), progressive heart failure (n = 4) or heart failure-related death (n = 1) and stroke (n = 4). The 4 patients who underwent aneurysmectomy had no adverse events. Patients with SCD had a lower ejection fraction (P = 0.004) and a larger left ventricular end-diastolic diameter (P < 0.001) than nonoperated survivors. CONCLUSIONS: Apical aneurysm is not rare in patients with HCM and it confers an extremely poor prognosis. Early aggressive therapies should be considered for this entity and prophylactic aneurysmectomy may be an option. PMID- 26802766 TI - Leukemia Cutis in Chronic Myelomonocytic Leukemia. PMID- 26802767 TI - Cardiac Arrhythmias and Abnormal Electrocardiograms After Acute Stroke. AB - Cardiac arrhythmias and electrocardiogram (ECG) abnormalities occur frequently but are often underrecognized after strokes. Acute ischemic and hemorrhagic strokes in some particular area of brain can disrupt central autonomic control of the heart, precipitating cardiac arrhythmias, ECG abnormalities, myocardial injury and sometimes sudden death. Identification of high-risk patients after acute stroke is important to arrange appropriate cardiac monitoring and effective management of arrhythmias, and to prevent cardiac morbidity and mortality. More studies are needed to better clarify pathogenesis, localization of areas associated with arrhythmias and practical management of arrhythmias and abnormal ECGs after acute stroke. PMID- 26802768 TI - Giant Intracranial Aneurysm Masquerading in the Sella. PMID- 26802769 TI - Streptococcus pyogenes: Acute Proctosigmoiditis, Bacteremia and Death in a Healthy Adult. PMID- 26802770 TI - Centrilobular Cysts of the Lung. PMID- 26802771 TI - TREM2 modifies microglial phenotype and provides neuroprotection in P301S tau transgenic mice. AB - As a novel risk gene for Alzheimer's disease (AD), triggering receptor expressed on myeloid cells 2 (TREM2) gene encodes a type I transmembrane receptor that is uniquely expressed by the microglia in the brain. Emerging evidence indicates a strong association between TREM2 and tau pathology in the cerebral spinal fluid or brain tissue of AD patients. In line with these clinical findings, we found that TREM2 was upregulated in the brain of P301S mice, an animal model of tau pathology, during disease progression. However, despite this information, the precise role of TREM2 in tau pathology remains largely unknown. In our recent studies, we revealed that silencing microglial TREM2 expression in P301S mice exacerbated spatial cognitive deficits and tau pathology. Based on this evidence, we hypothesized that TREM2 might exert a protective effect in tau-related neurodegenerative diseases. In the present study, to test this hypothesis, a lentiviral-mediated strategy was employed to selectively overexpress TREM2 on microglia in the brain of P301S mice. For the first time, we showed that TREM2 overexpression rescued spatial cognitive impairments and ameliorated neuropathologies including neuronal and synaptic loss as well as tau hyperphosphorylation. Meanwhile, this protective effect was likely attributed to the suppression of neuroinflammation and subsequent attenuation of tau kinase activity, since the expression of pro-inflammatory cytokines including Tnf, Il1b and Il6 as well as the activity of tau kinase including glycogen synthase kinase 3beta and cyclin-dependent kinase 5 was significantly reduced following TREM2 overexpression. Additionally, the suppressed neuroinflammation might be ascribed to the M2 activation of microglia induced by TREM2, as the expression of M2 phenotype makers including Arg1, Retnla, Il4 and Il10 was markedly increased. Taken together, these findings support the concept of TREM2 as a valuable target against AD as well as other tau-related neurodegenerative diseases. PMID- 26802772 TI - Here/In This Issue and There/Abstract Thinking: Risk Calculators in Child Psychiatry. PMID- 26802773 TI - "Failure to Launch": Shaping Intervention for Highly Dependent Adult Children. PMID- 26802774 TI - Structural Vestiges of Early Fearful Temperament in the Adult Brain. PMID- 26802775 TI - The National Institute of Mental Health Research Domain Criteria and Clinical Research in Child and Adolescent Psychiatry. AB - OBJECTIVE: This review discusses the relevance of the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) to clinical research in child and adolescent psychiatry. METHOD: We summarize the characteristics of the NIMH RDoC project and then provide examples of RDoC designs that are of relevance to clinical investigators in child and adolescent psychiatry. The final section addresses questions regarding the impact of RDoC on clinical care. RESULTS: RDoC encourages investigators to investigate psychopathology dimensionally: greater or lesser degrees of healthy/adapted functioning of neurobiological, cognitive, and behavioral processes (constructs) that cut across current diagnostic categories. Elucidation of the developmental components of RDoC constructs is needed to ensure they are fully validated. Integrating RDoC approaches into clinical research of child and adolescent psychopathology is contributing to our understanding of development as an aspect of the heterogeneity within DSM disorders and commonalities across seemingly disparate disorders. Continued efforts promise to also explain the processes that lead to mental illness in at risk populations. CONCLUSION: Incorporating an RDoC approach in clinical research in child and adolescent psychiatry promises to be a fruitful avenue of research into the root causes and manifestations of mental illness, which will eventually lead to more precise treatments. Although the long-term aspiration of RDoC is to help reduce the burden of suffering for those with mental illnesses, it is not intended to be used for practical clinical purposes at this early stage. PMID- 26802776 TI - Associations Between Peer Victimization and Suicidal Ideation and Suicide Attempt During Adolescence: Results From a Prospective Population-Based Birth Cohort. AB - OBJECTIVE: To test whether adolescents who are victimized by peers are at heightened risk for suicidal ideation and suicide attempt, using both cross sectional and prospective investigations. METHOD: Participants are from the Quebec Longitudinal Study of Child Development, a general population sample of children born in Quebec in 1997 through 1998 and followed up until 15 years of age. Information about victimization and serious suicidal ideation and suicide attempt in the past year was obtained at ages 13 and 15 years from self-reports (N = 1,168). RESULTS: Victims reported concurrently higher rates of suicidal ideation at age 13 years (11.6-14.7%) and suicide attempt at age 15 years (5.4 6.8%) compared to those who had not been victimized (2.7-4.1% for suicidal ideation and 1.6-1.9% for suicide attempt). Being victimized by peers at 13 years predicted suicidal ideation (odds ratio [OR] = 2.27; 95% CI = 1.25-4.12) and suicide attempt (OR = 3.05, 95% CI = 1.36-6.82) 2 years later, even after adjusting for baseline suicidality and mental health problems and a series of confounders (socioeconomic status, intelligence, family's functioning and structure, hostile-reactive parenting, maternal lifetime suicidal ideation/suicide attempt). Those who were victimized at both 13 and 15 years had the highest risk of suicidal ideation (OR = 5.41, 95% CI = 2.53-11.53) and suicide attempt (OR = 5.85, 95% CI = 2.12-16.18) at 15 years. CONCLUSION: Victimization is associated with an increased risk of suicidal ideation and suicide attempt over and above concurrent suicidality and prior mental health problems. The longer the history of victimization, the greater the risk. PMID- 26802777 TI - Autism Spectrum Disorders and Other Mental Health Problems: Exploring Etiological Overlaps and Phenotypic Causal Associations. AB - OBJECTIVE: Recent studies have highlighted the impact of coexisting mental health problems in autism spectrum disorders (ASD). No twin studies to date have reported on individuals meeting diagnostic criteria of ASD. This twin study reports on the etiological overlap between the diagnosis of ASD and emotional symptoms, hyperactivity, and conduct problems measured with the Strengths and Difficulties Questionnaire. METHOD: Genetic and environmental influences on the covariance between ASD and coexisting problems were estimated, in line with the correlated risks model prediction. Phenotypic causality models were also fitted to explore alternative explanations of comorbidity: namely, that coexisting problems are the result of or result in ASD symptoms; that they increase recognition of ASD; or that they arise due to an over-observation bias/confusion when differentiating between phenotypes. RESULTS: More than 50% of twins with broad spectrum/ASD met the borderline/abnormal levels cut-off criteria for emotional symptoms or hyperactivity, and approximately 25% met these criteria for the 3 reported problems. In comparison, between 13% and 16% of unaffected twins scored above the cut-offs. The phenotypic correlation between ASD and emotional symptoms was explained entirely by genetic influences and accompanied by a moderate genetic correlation (0.42). The opposite was true for the overlap with conduct problems, as nonshared-environmental factors had the strongest impact. For hyperactivity, the best-fitting model suggested a unidirectional phenotypic influence of hyperactivity on ASD. CONCLUSION: Our findings suggest a possible effect of hyperactivity on identification of ASD. The lack of genetic influences on conduct problems-ASD overlap further supports the genetic independence of these 2 phenotypes. Finally, the co-occurrence of emotional symptoms in ASD, compared to other co-occurring problems, is completely explained by common genetic effects. PMID- 26802778 TI - Clinical Correlates of Hoarding With and Without Comorbid Obsessive-Compulsive Symptoms in a Community Pediatric Sample. AB - OBJECTIVE: We assessed the prevalence and clinical correlates of hoarding, with and without obsessive-compulsive (OC) symptoms, in a community-based pediatric sample. METHOD: We measured hoarding and OC symptoms using the Toronto Obsessive Compulsive Scale (TOCS) in 16,718 youth aged 6 to 17 years in the community. We classified participants with high and low symptom counts for hoarding and OC into 4 groups: hoarding+OC; hoarding-only; OC-only; and control (no OC or hoarding symptoms). We compared these 4 groups on parent- or self-reported medical and psychiatric conditions, anxiety symptoms measured with the Child Behavior Checklist (CBCL), and attention-deficit/hyperactivity disorder (ADHD) symptoms measured with the Strengths and Weaknesses of Attention-Deficit/Hyperactivity Disorder Symptoms and Normal Behavior Scale (SWAN). RESULTS: Almost 10% of participants were in the high hoarding group. Of these participants, 40% did not fall into the high OC group. The prevalence of reported psychiatric disorders (e.g., ADHD, autism spectrum disorder, obsessive-compulsive disorder) was greater in the hoarding (hoarding+OC and hoarding-only) and OC groups (hoarding+OC and OC only) than in the nonhoarding (OC-only and control) and non-OC groups (hoarding only and control), respectively. ADHD, specifically inattentive, symptoms were more common in the hoarding-only than in the OC-only group while anxiety symptoms were more common in the OC-only than in the hoarding-only group. CONCLUSION: In a community pediatric sample, hoarding symptoms occurred in both the presence and absence of obsessive-compulsive symptoms. Hoarding symptoms alone had some unique clinical correlates, in particular, more inattentive ADHD symptoms and fewer anxiety symptoms. These findings suggest that hoarding is distinct from OC traits in youth. PMID- 26802779 TI - Early Childhood Behavioral Inhibition Predicts Cortical Thickness in Adulthood. AB - OBJECTIVE: Behavioral inhibition (BI) during early childhood predicts risk for anxiety disorders and altered cognitive control in adolescence. Although BI has been linked to variation in brain function through adulthood, few studies have examined relations between early childhood BI and adult brain structure. METHOD: The relation between early childhood BI and cortical thickness in adulthood was examined in a cohort of individuals followed since early childhood (N = 53, mean age 20.5 years). Analyses tested whether anxiety and/or cognitive control during adolescence moderated relations between BI and cortical thickness. Cognitive control was measured with the Eriksen Flanker Task. Initial analyses examined cortical thickness in regions of interest previously implicated in BI, anxiety disorders, and cognitive control: dorsal anterior cingulate (dACC), anterior insula (aI), and subgenual anterior cingulate (sgACC); and volumes of the amygdala and hippocampus. Exploratory analyses examined relations across the prefrontal cortex. RESULTS: BI during early childhood related to thinner dACC in adulthood. Neither anxiety nor cognitive control moderated this relation. A stronger congruency effect on the Eriksen Flanker Task during adolescence independently related to thinner dACC in adulthood. Higher anxiety during adolescence related to thicker cortex in the right ventrolateral prefrontal cortex (VLPFC) in adulthood among those with low BI as children. CONCLUSION: Temperament in early childhood and the interaction between temperament and later anxiety relate to adult brain structure. These results are consistent with prior work associating BI and anxiety with functional brain variability in the dACC and VLPFC. PMID- 26802781 TI - Mode of Anisotropy Reveals Global Diffusion Alterations in Attention Deficit/Hyperactivity Disorder. AB - OBJECTIVE: Diffusion tensor imaging (DTI) can identify structural connectivity alterations in attention-deficit/hyperactivity disorder (ADHD). Most ADHD DTI studies have concentrated on regional differences in fractional anisotropy (FA) despite its limited sensitivity to complex white matter architecture and increasing evidence of global brain differences in ADHD. Here, we examine multiple DTI metrics in separate samples of children and adults with and without ADHD with a principal focus on global between-group differences. METHOD: Two samples: adults with ADHD (n = 42) and without (n = 65) and children with ADHD (n = 82) and without (n = 80) were separately group matched for age, sex, and head motion. Five DTI metrics (FA, axial diffusivity, radial diffusivity, mean diffusivity, and mode of anisotropy) were analyzed via tract-based spatial statistics. Group analyses tested for diagnostic differences at the global (averaged across the entire white matter skeleton) and regional level for each metric. RESULTS: Robust global group differences in diffusion indices were found in adults, with the largest effect size for mode of anisotropy (MA; Cohen's d = 1.45). Global MA also differed significantly between groups in the pediatric sample (d = 0.68). In both samples, global MA increased classification accuracy compared to the model with clinical Conners' ADHD ratings alone. Regional diagnostic differences did not survive familywise correction for multiple comparisons. CONCLUSION: Global DTI metrics, particularly the mode of anisotropy, which is sensitive to crossing fibers, capture connectivity abnormalities in ADHD across both pediatric and adult samples. These findings highlight potential diffuse white matter microarchitecture differences in ADHD. PMID- 26802780 TI - Severity of Cortical Thinning Correlates With Schizophrenia Spectrum Symptoms. AB - OBJECTIVE: This study investigated the relationship between regional cortical gray matter thinning and symptoms of schizophrenia spectrum personality disorders (PDs) in siblings of patients with childhood-onset schizophrenia (COS). METHOD: A total of 66 siblings of patients with COS were assessed for symptoms of schizophrenia spectrum PDs (avoidant, paranoid, schizoid, schizotypal). Structural magnetic resonance images were obtained at approximately 2-year intervals from the siblings and from 62 healthy volunteers matched for age, sex, ethnicity, and handedness. Cortical thickness measures were extracted. Mixed effect regression models were used to test the relationship between symptoms and cortical gray matter thickness in siblings. Cortical thinning was also tested longitudinally in healthy volunteers and siblings. RESULTS: Cortical thinning was found to correlate with symptoms of schizotypal and, to a lesser extent, schizoid PDs. Thinning was most pronounced in the left temporal and parietal lobes and right frontal and parietal regions. Gray matter loss was found to be continuous with that measured in COS. Longitudinal thinning trajectories were found not to differ between siblings and healthy volunteers. CONCLUSION: The present investigation of cortical thinning in siblings of patients with COS indicates that symptoms of schizophrenia spectrum PDs correlate with regional gray matter loss. This finding supports the idea of cortical thinning as a schizophrenia endophenotype. PMID- 26802783 TI - Five-Year Outcomes of Ranibizumab With Prompt or Deferred Laser Versus Laser or Triamcinolone Plus Deferred Ranibizumab for Diabetic Macular Edema. AB - PURPOSE: To compare long-term vision and anatomic effects of ranibizumab with prompt or deferred laser vs laser or triamcinolone + laser with very deferred ranibizumab in diabetic macular edema (DME). DESIGN: Randomized clinical trial. METHODS: Eight hundred and twenty-eight study eyes (558 [67%] completed the 5 year visit), at 52 sites, with visual acuity 20/32 to 20/320 and DME involving the central macula were randomly assigned to intravitreous ranibizumab (0.5 mg) with either (1) prompt or (2) deferred laser; (3) sham injection + prompt laser; or (4) intravitreous triamcinolone (4 mg) + prompt laser. The latter 2 groups could initiate ranibizumab as early as 74 weeks from baseline, for persistent DME with vision impairment. The main outcome measures were visual acuity, optical coherence central subfield thickness, and number of injections through 5 years. RESULTS: At 5 years mean (+/- standard deviation) change in Early Treatment Diabetic Retinopathy Study visual acuity letter scores from baseline in the ranibizumab + deferred laser (N = 111), ranibizumab + prompt laser (N = 124), laser/very deferred ranibizumab (N = 198), and triamcinolone + laser/very deferred ranibizumab (N = 125) groups were 10 +/- 13, 8 +/- 13, 5 +/- 14, and 7 +/- 14, respectively. The difference (95% confidence interval) in mean change between ranibizumab + deferred laser and laser/very deferred ranibizumab and triamcinolone + laser/very deferred ranibizumab was 4.4 (1.2-7.6, P = .001) and 2.8 (-0.9 to 6.5, P = .067), respectively, at 5 years. CONCLUSIONS: Recognizing limitations of follow-up available at 5 years, eyes receiving initial ranibizumab therapy for center-involving DME likely have better long-term vision improvements than eyes managed with laser or triamcinolone + laser followed by very deferred ranibizumab for persistent thickening and vision impairment. PMID- 26802784 TI - On the origin of blood cells--hematopoiesis revisited. PMID- 26802786 TI - Ethnomedicinal survey of a maroon community in Brazil's Atlantic tropical forest. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Considerable medicinal plant research in Brazil has focused on indigenous and mixed-race (caboclo and caicara) communities, but relatively few studies have examined the medicinal plants and associated healing traditions of the descendants of enslaved Africans. This study surveyed the medicinal plants employed by a relatively isolated maroon community of Afro Brazilians in the Atlantic coastal rainforests of Bahia, Brazil, a global biodiversity hotspot. The studied community is exceptional in that the residents were defacto slaves until several years ago, with no access to western medicine. We examined the following questions: 1) What medicinal plants are used in this community? 2) What are the principal taxonomic groups, life forms, source habitats, and geographical origins? 3) What species stand out as measured by use value and frequency indices? and 4) Is the community's geographical isolation and African ancestry reflected in their medicinal uses of the local flora? MATERIALS AND METHODS: The study was carried out in the Quilombo Salamina Putumuju maroon community in Bahia, Brazil. Data were collected from May to October 2014 from 74 individuals (37 men and 37 women) by means of semi-structured interviews, walk in the woods, and vouchering of identified species. We used the Cultural Value Index (CV), the Relative Frequency Index (RF), and the Use Value Index (UV) to determine the importance of medicinal plant resources. Continuity of African medicinal plant uses and traditions was determined through self-reporting and comparison with previously published works. RESULTS: We recorded 118 medicinal plant species distributed in 100 genera and 51 families. The best represented families were: Asteraceae, Fabaceae, Lamiaceae and Myrtaceae. Most plant medicines were used to treat respiratory, digestive systems, genitourinary, and skin problems. The most common medicinal life form was herbs (44%), followed by trees (28%) and shrubs (18%). Native species (55%) were used somewhat more than exotic species (45%), and non-cultivated species (51%) were slightly more numerous than cultivated species (49%). In spite of abundant nearby old-growth forests, trails and gardens were the most common collection sites. A mean of 13.2 medicinal plant species were cited per participant. The highest CV was recorded for Cymbopogon citratus (0.20) followed by Lippia alba (0.19) and Stryphnodendron cf. adstringens (0.17). The highest RF included C. citratus (0.69), L. alba (0.59), and Eugenia uniflora (0.55). The highest UV figures were recorded for S. cf. adstringens (1.68), followed by Sida cf. cordifolia (0.97) and C. citratus (0.93).Fifteen species (13%) of this maroon medicinal flora trace their ancestry to Africa or African-derived healing traditions. CONCLUSION: The Salamina maroon community maintains considerable knowledge of the medicinal value of the local flora. However, little of this knowledge is derived from the surrounding old growth tropical forests. Their pharmacopoeia is a hybrid mix of wild and cultivated species, natives and exotics. Among those species representing the community's isolation and African ancestry, most are associated with spiritual and magical medicine. PMID- 26802787 TI - Environmental dynamics modulate covariation of choice and timing. AB - Response allocation between delayed reinforcers is presumably a function of the discrimination of those delays. In the present experiment, we analyzed the functional relation between response allocation and temporal discrimination across different environmental dynamics. Three pigeons pecked for food in a concurrent-chain schedule. Concurrent variable-interval initial links produced fixed-interval (FI) terminal links. Start and stop times, single-trial measures of temporal discrimination, were obtained from occasional 'no-food' terminal links. In dynamic, rapid-acquisition conditions, terminal links were FI 10s and 20s and the location of the initial link leading to the shorter terminal link varied unpredictably across sessions. In the static conditions, both terminal links were either "uniform" FI 15-s schedules or one terminal link was "fixed" at FI 10s and the other at 20s. Response allocation and start and stop times adjusted within sessions in dynamic conditions and across sessions of static conditions. Residuals from regressions of expected on programmed immediacy ratios were positively correlated to a greater magnitude in dynamic than static conditions. This change in residual covariation demonstrated that environmental dynamics modulated the relation between choice and timing. PMID- 26802785 TI - The effects of Tao-Hong-Si-Wu on hepatic necroinflammatory activity and fibrosis in a murine model of chronic liver disease. AB - BACKGROUND: Tao-Hong-Si-Wu decoction (THSWD) is a traditional Chinese herbal medicine that has been used for centuries in the treatment of Chinese patients with chronic liver disease. Recently, THSWD has been reported to alter vascular endothelial growth factor (VEGF) induced angiogenesis, raising the possibility that in addition to its anti-inflammatory properties; THSWD might also inhibit hepatic blood flow associated fibrosis. AIM: To document the effects of THSWD on hepatic necroinflammatory disease activity, fibrosis and VEGF signaling in a murine model of chronic liver disease. METHODS: Sixty adult mice were equally divided into six study groups. Five groups were exposed to subcutaneous carbon tetrachloride (0.1 ml/10 g BW) for six weeks. Three of the five groups were treated with different concentrations of THSWD (4.25, 8.50, 17.00 g/kg), one with 0.1mg/kg of Colchicine (positive control), and one with physiologic saline (negative control). Mice in the sixth group were not exposed to CCl4 and remained untreated (healthy controls). Liver enzymes/function tests, hyaluronic acid and laminin levels were measured in serum, and hepatic histology, VEGF, Flt-1 and kinase insert domain-containing receptor (KDR), Akt and phosphorylated Akt (pAkt) expression were documented in liver tissue at the end of treatment. RESULTS: Hepatic necroinflammatory disease activity and fibrosis were significantly attenuated in THSWD treated mice in a dose dependent manner. These beneficial results were similar and often exceeded those achieved with Colchicine. In addition, VEGF, Flt-1, KDR, Akt and pAkt mRNA and protein expression were reduced in TSHWD treated mice. CONCLUSIONS: In this animal model of chronic liver disease, THSWD decreased hepatic necroinflammatory disease and fibrosis. Inhibition of VEGF expression and downstream signaling were associated with these findings. Further studies with this and other TCMs as treatment for chronic liver disease are warranted. PMID- 26802788 TI - Pre-pregnancy maternal obesity in Greece: A case-control analysis. AB - BACKGROUND-AIMS: Pre-pregnancy obesity may cause significant health implications for both mother and neonate. Our study aims to investigate the association between pre-pregnancy Body Mass Index and the risk for cesarean section, admission to Neonatal Intensive Care Unit, macrosomia and preterm delivery, in a Mediterranean country. STUDY DESIGN: A matched retrospective case control analysis was conducted. SUBJECTS: The study population included all pregnant women (with known Body Mass Index data) who gave birth in the University Hospital of Patras between 1st of January 2003 and 31st of December 2008. OUTCOME MEASURES: Cases were defined as obese (338) or overweight (826) women. RESULTS: Overweight and obese women were at higher risk for cesarean section, NICU admission and preterm delivery (chi(2)(2)=36.877, p<0.001, chi(2) Imes and Burke (2014) =6.586, p=0.037 and chi(2) Imes and Burke (2014) =7.227, p=0.027 respectively). Neonatal mean birthweight was higher among obese and overweight women (p<0.0001). CONCLUSIONS: Both obese and overweight pregnancies should be considered as high risk pregnancies, due to more frequent adverse pregnancy outcomes (cesarean delivery, preterm delivery and NICU admission). PMID- 26802789 TI - Social contexts of momentary craving to smoke among Korean American emerging adults. AB - INTRODUCTION: Korean American emerging adult (KAEA) smokers represent a culturally and developmentally unique population constituted of primarily light, intermittent smokers. Sociocultural contexts might play an important role in contributing to instances of acute cigarette craving and motivation to smoke in this population; yet, research testing such hypotheses is scant. The current study tests whether and how social contexts are associated with the craving among KAEA smokers. METHODS: Seventy-eight daily KAEA smokers, who smoke 4+ cigs/day, participated in a 7-day ecological momentary assessment (EMA), in which participants responded to both signal-contingent (random) and event-contingent (smoking) prompts to answer surveys on their mobile phones (prompt-level n=1377; 603 random +774 smoking prompts). Nicotine dependence was measured at baseline; cigarette craving, negative affect, presence of others smoking, social contexts were measured with EMA. RESULTS: Modeling of within-participant variation and covariation showed that being with Korean friends (vs. alone) was associated with increased levels of momentary craving. This association between Korean friends and craving disappeared when adjusted for presence of others smoking, which was a strong predictor of momentary craving. The positive association between Korean friends and craving was amplified immediately prior to smoking (vs. non-smoking random) instances. CONCLUSIONS: Being with Korean friends might serve as a culturally-specific salient smoking cue, which might have been learned throughout their smoking history. Our data also showed that increased craving associated with Korean friends may represent social settings that primarily involve cigarette smoking. Given our findings on cigarette use among KAEA's social network, addressing cigarette use as a group behavior might be a fruitful intervention strategy. PMID- 26802791 TI - Low cost of gastric acid secretion during digestion in ball pythons. AB - Due to their large metabolic responses to digestion (specific dynamic action, SDA), snakes represent an interesting animal group to identify the underlying mechanisms for the postprandial rise in metabolism. The SDA response results from the energetic costs of many different processes ranging over prey handling, secretions by the digestive system, synthesis of enzymes, plasticity of most visceral organs, as well as protein synthesis and nitrogen excretion. The contribution of the individual mechanisms, however, remains elusive. Gastric acid secretion has been proposed to account for more than half of the SDA response, while other studies report much lower contributions of the gastric processes. To investigate the energetic cost of gastric acid secretion, ball pythons (Python regius) were fed meals with added amounts of bone meal (up to 25 g bone meal kg( 1) snake) to achieve a five-fold rise in the buffer capacity of the meals. Direct measurements within the stomach lumen showed similar reduction in gastric pH when buffer capacity was increased, but we found no effects on the rise in oxygen consumption over the first three days of digestion. There was, however, a slower return of oxygen consumption to resting baseline. We conclude that gastric acid secretion only contributes modestly to the SDA response and propose that post absorptive processes, such as increased protein synthesis, are likely to underlie the SDA response. PMID- 26802790 TI - Anxiety sensitivity facets in relation to tobacco use, abstinence-related problems, and cognitions in treatment-seeking smokers. AB - Anxiety sensitivity (AS)--fear of anxiety-related experiences--has been implicated in smoking motivation and maintenance. In a cross-sectional design, we examined AS facets (physical, cognitive, and social concerns) in relation to tobacco use, abstinence-related problems, and cognitions in 473 treatment-seeking smokers. After controlling for sex, race, age, educational attainment, hypertension status, and neuroticism, linear regression models indicated that AS physical and cognitive concerns were associated with tobacco dependence severity (beta=.13-.14, p<.01), particularly the severity of persistent smoking regardless of context or time of day (beta=.14-.17, p<.01). All three AS facets were related to more severe problems during past quit attempts (beta=.23-.27, p<.001). AS cognitive and social concerns were related to negative affect reduction smoking motives (beta=.14, p<.01), but only the social concerns aspect of AS was related to pleasurable relaxation smoking motives and positive and negative reinforcement related smoking outcome expectancies (beta=.14-.17, p<.01). These data suggest that AS physical and cognitive concerns are associated with negative reinforcement-related smoking variables (e.g., abstinence-related problems), whereas the social concerns aspect of AS is associated with positive and negative reinforcement-related smoking variables. Together with past findings, current findings can usefully guide AS-oriented smoking cessation treatment development and refinement. PMID- 26802792 TI - Gender differences in carpal tunnel relative cross-sectional area: a possible causative factor in idiopathic carpal tunnel syndrome. AB - Previous research has not established a consistent difference in hand size or carpal tunnel cross-sectional area between patients with and without carpal tunnel syndrome. We tested the hypothesis that there would be no difference in relative carpal tunnel sizes between men and women. We defined relative carpal tunnel size as the cross-sectional areas at the inlet (level of the pisiform) and outlet (level of the hook of the hamate) of the carpal tunnel divided by the length of the capitate (as a measure of hand size). We made the measurements on the magnetic resonance imaging scans of 50 men and 50 women taken for symptoms unrelated to carpal tunnel syndrome. The mean relative cross-sectional area was appreciably smaller in women than men (p < 0.05). This suggests that the carpal tunnel cross-sectional area relative to the size of the hand is constitutionally smaller in women than in men. This could in theory be a significant factor in patients developing carpal tunnel syndrome. LEVEL OF EVIDENCE: V. PMID- 26802793 TI - The power of positive thinking: Pathological worry is reduced by thought replacement in Generalized Anxiety Disorder. AB - Worry in Generalized Anxiety Disorder (GAD), takes a predominantly verbal form, as if talking to oneself about possible negative outcomes. The current study examined alternative approaches to reducing worry by allocating volunteers with GAD to conditions in which they either practiced replacing the usual form of worry with images of possible positive outcomes, or with the same positive outcomes represented verbally. A comparison control condition involved generating positive images not related to worries. Participants received training in the designated method and then practiced it for one week, before attending for reassessment, and completing follow-up questionnaires four weeks later. All groups benefited from training, with decreases in anxiety and worry, and no significant differences between groups. The replacement of worry with different forms of positive ideation, even when unrelated to the content of worry itself, seems to have similar beneficial effects, suggesting that any form of positive ideation can be used to effectively counter worry. PMID- 26802794 TI - Anterior Urethra Reconstruction With Lateral Lingual Mucosa Harvesting Technique. AB - OBJECTIVE: To describe a new technique for harvesting the long lingual mucosal graft (LMG) to repair the long-segment urethral strictures. METHODS: We performed a retrospective observational study of patients from whom LMGs were harvested from the lateral lining of the tongue for the long-segment anterior urethral strictures repair from 2012 to 2014 at the Shanghai Sixth People's Hospital. Patients who had 12 months minimum follow-up were included. Patients with incomplete clinical records were excluded. The LMG was applied on the urethra according to the dorsal onlay technique. RESULTS: The primary outcome of the study was the postoperative failure-free survival rate. The secondary outcome was the rate of early and late complications at the harvesting site. Success was defined as Qmax >12 ml/s and no postoperative procedures. One hundred and one patients were included. Median stricture length was 7.1 +/- 3.6 cm; median LMG length was 7.2 +/- 3.6 cm. The success rate was 81.2% with a median follow-up of 23 months. Complications at the donor site had occurred in 41 patients at 6 months follow-up, and persisted in 18 patients at the 12-months follow-up. A bilateral harvest and harvest length were the main factors influencing complication rate (P = .0038 for 6 months and P = .1112 for 12 months). Almost half of donor site complications subsided within 12 months (P = .0018). CONCLUSION: In patients requiring long oral grafts >7 cm to repair anterior strictures, a valid option is to harvest the graft from the lateral lining of the tongue. PMID- 26802795 TI - Transitional Cell Carcinoma in the Pediatric Patient: A Review of the Literature. AB - Transitional cell carcinoma (TCC) is extremely rare in children, with fewer than 30 cases reported in patients under 10 years old. It is thought that pediatric TCC is fundamentally different than TCC in adults; however, there are no specific guidelines for management or surveillance. Furthermore, the addition of papillary urothelial neoplasm of low malignant potential as a diagnosis has changed the management of lesions previously considered malignant. This review aims to investigate the difference between TCC in adults and children, to report current strategies for management of pediatric TCC, and to analyze the effects of the new grading system. PMID- 26802796 TI - Incidental Diagnosis of Giant Cell Tumor After Urachal Remnant Removal in a Thalassemic Child. AB - Urachal anomalies are relatively uncommon; they usually present in childhood as urachal cysts, urachal sinuses, diverticula, and patent urachus. The malignant involvement of the urachus, although rare in children, is commonly found in adulthood when adenocarcinoma accounts for the majority of the cases, representing up to 20-30% of all adenocarcinomas of the bladder. Urachal tumors of variable histology have been reported in children and adolescents as single case report. We present the first case of a 4-year-old thalassemic boy, with an incidental finding of giant cell tumor arising in an urachal remnant. PMID- 26802798 TI - Re: Simoes Paco J, Jorge Pereira B.: New Therapeutic Perspectives in Premature Ejaculation (Urology 2016; 88:87-92). A Rebuttal: Premature Ejaculation is Not a Male Sexual Dysfunction. PMID- 26802797 TI - Management of Penile Cancer. AB - Although rare, penile cancer carries high morbidity and mortality particularly when pertaining to the management of locally advanced or metastatic disease. The current scientific literature lacks level 1 evidence and current guidelines are based largely on retrospective studies and small single center studies. Despite these limitations, there has been paradigm shifts in the management of both local and systemic disease. Current guidelines emphasize penile sparing strategies, minimizing morbidity from surgical management of loco-regional metastasis and multimodal management of bulky inguinal lymph node metastases. The present review highlights the current state of knowledge and recommended treatment strategies of penile carcinoma. PMID- 26802799 TI - Robotic Level III IVC Tumor Thrombectomy: Duplicating the Open Approach. AB - OBJECTIVES: To describe our surgical technique for robotic radical nephrectomy and thrombectomy for renal cell carcinoma and associated level III inferior vena cava (IVC) thrombus with retroperitoneal lymph node dissection. METHODS: The patient is a 75-year-old Caucasian man with a 10-cm right renal neoplasm and associated level III tumor thrombus. After preoperative imaging was reviewed, a robotic approach was planned. Real-time intraoperative transesophageal ultrasonography was performed to assess the cranial extent of tumor thrombus. The major steps of our technique include early inter-aortocaval control of the right renal artery, circumferential mobilization of the IVC, contralateral renal vein control, cavotomy, thrombectomy, and reconstruction of the IVC. RESULTS: Operative time was 5 hours and 53 minutes (353 minutes) with 150 mL estimated blood loss. The patient was allowed to have a clear liquid diet immediately after surgery and was discharged home on postoperative day 3. Final pathology demonstrated a 9.8-cm clear cell renal cell carcinoma, nuclear grade 3 with a pT3bN1 stage. CONCLUSIONS: With adequate team experience and preparation, robotic radical nephrectomy and IVC tumor thrombectomy for level III tumor thrombus is challenging but feasible in select patients. Herein we describe our robotic technique which duplicates the open approach. This minimally invasive approach may offer lower estimated blood loss, improved pain control, and expedited recovery. PMID- 26802800 TI - Six Weeks of Fluoroquinolone Antibiotic Therapy for Patients With Elevated Serum Prostate-specific Antigen Is Not Clinically Beneficial: A Randomized Controlled Clinical Trial. AB - OBJECTIVE: To evaluate asymptomatic men with elevated serum prostate-specific antigen (PSA) to determine whether a 6-week course of fluoroquinolone antibiotics lowers serum PSA and affects recommendations for prostate biopsy. MATERIALS AND METHODS: A randomized, single-center prospective trial of 150 men with an initial elevated PSA was conducted. Patients were randomized to 6 weeks of ciprofloxacin or observation. Those patients with persistently elevated PSA were recommended to proceed with transrectal ultrasound-guided 12-core biopsy. Those with reduced PSA were offered transrectal ultrasound-guided biopsy but could opt to continue serial digital rectal examination/PSA. Patients were followed an average of 4.6 years to assess trends in PSA and biopsy results. RESULTS: Of 136 men who completed the trial, 63 were in the treatment and 73 were in the observation group. The average PSA change from baseline was borderline statistically significant with a change of -0.68 ng/mL in the treatment arm and 0.01 ng/mL in the observation arm (P = .052). Of those who underwent biopsy, prostate cancer was diagnosed in the first biopsy in 24 (63%) of the treatment vs 27 (52%) of the observation group (P = .60) over follow-up. CONCLUSION: In a cohort of asymptomatic men with elevated PSA, there was only a borderline statistically significant change in serum PSA between patients randomized to a 6-week course of fluoroquinolones vs observation, and there was no difference in positive prostate biopsy results. Our clinical recommendation is one should not treat patients with elevated serum PSA with antibiotics in the absence of clinical symptoms of prostatitis. PMID- 26802801 TI - Characterizing the Morbidity of Postchemotherapy Retroperitoneal Lymph Node Dissection for Testis Cancer in a National Cohort of Privately Insured Patients. AB - OBJECTIVE: To characterize morbidity of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for testis cancer, we analyze a contemporary national database. PC-RPLND is the standard for residual radiographic masses >=1 cm (nonseminoma) and positron emission tomography-avid masses >=3 cm (seminoma). Morbidity for PC-RPLND is greater than primary RPLND, which may be mitigated by performing surgery at a high-volume cancer center. METHODS: Current Procedural Terminology and International Classification of Diseases, Ninth Edition codes identified men with testis cancer undergoing PC- or primary RPLND in MarketScan (2007-2012). Multivariable logistic regression assessed factors associated with receiving adjunctive procedures (ie, nephrectomy, vascular reconstruction), prolonged hospitalization, and 90-day readmission. Geographic variables assessed regionalization of PC-RPLND. RESULTS: Of 559 men with claims for PC- or primary RPLND (206, 37% PC-RPLND), 19% of PC-RPLND underwent adjunctive procedures (vs 1% among RPLND, P < .01). For PC-RPLND, the nephrectomy rate was 10% and the vascular reconstruction rate was 8%. On multivariable analysis, PC-RPLND was associated with undergoing adjunctive procedures (odds ratio 41.9; 95% confidence interval 11.7, 150) and prolonged hospitalization (odds ratio 3.75; 95% confidence interval 1.68, 8.42) compared to primary RPLND. PC-RPLND was not associated with 90-day readmission. Up to 29% of PC-RPLNDs are performed in centers, billing just a single case through MarketScan in the 6 years studied. CONCLUSION: PC-RPLND is associated with adjunctive procedures and longer hospitalizations. Given the morbidity of PC-RPLND in this young patient population, efforts are needed to establish quality benchmarks for, reduce the morbidity of, and to accurately discriminate risk during patient discussions prior to this complex, specialized surgery. PMID- 26802802 TI - The Digital Footprint of Academic Urologists: Where Do we Stand? AB - OBJECTIVE: To characterize the digital footprint of academic urologists by examining their web search results and identifying patterns within them. MATERIALS AND METHODS: Faculty lists were obtained from the top 10 ranked Urology residency program websites. A standardized Google search for "First Name Last Name Degree" was then completed for each staff physician. The total number of results and type of sites returned were recorded and patterns contained within identified. RESULTS: A total of 247 staff physicians were identified, with 13-36 per institution. A median of 11 (interquartile range: 10-12) search results returned for each person. Most (number = 231) staff had at least 1 rating site returned, with a mean of 3.50 (standard deviation: 1.45) noted. Overall, 3.44 (1.39) pages related to the practice were listed. Social media use was poorly visible, with a median 0 [0-1] results listed and only 7 Twitter accounts observed. More than half of sites, 6.34 (1.87) on average, were physician controllable content. Having certain types of results was significantly associated with fewer ratings sites. Having an additional degree was also associated with significantly fewer ratings sites and more sites with physician controllable content. CONCLUSION: The digital footprint of academic urologists contains more physician-controllable content than noncontrollable information; however, social media visibility in this group is poor. Optimization of the digital identity of academic urologists may be possible by exploiting the patterns observed in this study. PMID- 26802803 TI - Derivation of an endogenous small RNA from double-stranded Sox4 sense and natural antisense transcripts in the mouse brain. AB - Natural antisense transcripts (NATs) are involved in cellular development and regulatory processes. Multiple NATs at the Sox4 gene locus are spatiotemporally regulated throughout murine cerebral corticogenesis. In the study, we evaluated the potential functional role of Sox4 NATs at Sox4 gene locus. We demonstrated Sox4 sense and NATs formed dsRNA aggregates in the cytoplasm of brain cells. Over expression of Sox4 NATs in NIH/3T3 cells generally did not alter the level of Sox4 mRNA expression or protein translation. Upregulation of a Sox4 NAT known as Sox4ot1 led to the production of a novel small RNA, Sox4_sir3. Its biogenesis is Dicer1-dependent and has characteristics resemble piRNA. Expression of Sox4_sir3 was observed in the marginal and germinative zones of the developing and postnatal brains suggesting a potential role in regulating neurogenesis. We proposed that Sox4 sense-NATs serve as Dicer1-dependent templates to produce a novel endo-siRNA- or piRNA-like Sox4_sir3. PMID- 26802804 TI - Organ-specific regulation of growth-defense tradeoffs by plants. AB - Plants grow while also defending themselves against phylogenetically unrelated pathogens. Because defense and growth are both costly programs, a plant's success in colonizing resource-scarce environments requires tradeoffs between the two. Here, we summarize efforts aimed at understanding how plants use iterative tradeoffs to modulate differential organ growth when defenses are elicited. First, we focus on shoots to illustrate how light, in conjunction with the growth hormone gibberellin (GA) and the defense hormone jasmonic acid (JA), act to finely regulate defense and growth programs in this organ. Second, we expand on the regulation of growth-defense trade-offs in the root, a less well-studied topic despite the critical role of this organ in acquiring resources in an environment deeply entrenched with disparate populations of microbes. PMID- 26802805 TI - The biosensor toolbox for plant developmental biology. AB - Plant development is highly interconnected with the metabolic state of tissues and cells. Current research efforts focus on the identification of the links and mechanisms that govern the interplay between metabolic and gene-regulatory networks. Genetically encoded sensors that allow detection of small molecules in vivo and at high spatio-temporal resolution promise to be the tools of choice for quantifying and visualizing the dynamics of metabolite flux in plants. We provide an overview about current approaches to measure signaling molecules, such as hormones, calcium and sugars, as well as for monitoring the metabolic state via energy equivalents and pH. Biosensors show great potential to address questions of plant development but there are also limitations where alternative approaches are needed. PMID- 26802806 TI - Zygotic genome activation in isogenic and hybrid plant embryos. AB - Zygotic genome activation (ZGA) is the onset of large-scale transcription that occurs after fertilization. In animal embryos, ZGA occurs after a period of transcriptional quiescence that varies between species. In plants, the timing of ZGA may also vary between species, and may or may not occur in a parent-of-origin dependent manner: some studies have shown a maternal bias in mRNA transcripts and gene activity in early embryogenesis, while other experiments have found the contribution of maternal and paternal genomes to be equal. In order to differentiate between maternal and paternal mRNAs, RNA sequencing studies of ZGA in plants have used embryos hybrid for polymorphic accessions. A recent genetic assay in Arabidopsis demonstrated significant variation in paternal allele activity between some hybrid combinations and isogenic embryos, as well as between different hybrid combinations, suggesting a possible source for conflicting results obtained by various experiments on paternal genome activation. We review recent literature on paternal genome activation studies in the zygote in both isogenic and hybrid embryos, and discuss possible explanations for the effects of hybridization on gene expression in early embryogenesis in plants. PMID- 26802807 TI - Molecular mechanisms of floral organ specification by MADS domain proteins. AB - Flower development is a model system to understand organ specification in plants. The identities of different types of floral organs are specified by homeotic MADS transcription factors that interact in a combinatorial fashion. Systematic identification of DNA-binding sites and target genes of these key regulators show that they have shared and unique sets of target genes. DNA binding by MADS proteins is not based on 'simple' recognition of a specific DNA sequence, but depends on DNA structure and combinatorial interactions. Homeotic MADS proteins regulate gene expression via alternative mechanisms, one of which may be to modulate chromatin structure and accessibility in their target gene promoters. PMID- 26802808 TI - Looking at the self in front of others: Neural correlates of attentional bias in social anxiety. AB - In social anxiety disorder (SAD), anxiety reactions are triggered by attentional bias to social threats that automatically appear in social situations. The present study aimed to investigate the neural basis and underlying resting-state pathology of attentional bias toward internal and external social threats as a core element of SAD. Twenty-two patients with SAD and 20 control subjects scanned functional magnetic resonance imaging during resting-state and while performing the visual search task. During the task, participants were exposed to internal threat (hearing participants' own pulse-sounds) and external threat (crowds in facial matrices). Patients showed activations in the lateral orbitofrontal cortex, rostral anterior cingulate cortex and insula in response to internal threat and activations in the posterior cingulate cortex and middle temporal gyrus in response to external threat. In patients, neural activity related to combined internal and external threats in the posterior cingulate cortex was inversely correlated with the functional connectivity strengths with the default mode network during resting-state. These findings suggest that attentional bias may stem from limbic and paralimbic pathology, and the interactive process of internally- and externally-focused attentional bias in SAD is associated with the self-referential function of resting-state. PMID- 26802809 TI - Sleep disturbance and obsessive-compulsive symptoms: Results from the national comorbidity survey replication. AB - A small body of developing research has found evidence for sleep disturbance in obsessive-compulsive disorder (OCD) and links between sleep disturbance and obsessive-compulsive symptoms (OCS) in unselected samples. However, the link between sleep disturbance and OCS is yet to be examined in a nationally representative sample. Furthermore, the extent to which the link between sleep disturbance and OCS is accounted for by symptoms of depression remains unclear. To address this gap in the literature, the present study examined the relationship between sleep disturbance and OCS in a nationally representative sample. Participants were assessed in the National Comorbidity Survey Replication (NCS-R; n = 2073). Consistent with predictions, results revealed that individuals with sleep disturbance reported increased OCS severity compared to individuals without sleep disturbance. Further, sleep disturbance severity was associated with OCS severity, even when controlling for depression (and other anxiety related disorders). This study is the first to link sleep disturbance and OCS in a nationally representative sample, and these findings highlight the unique role of sleep disturbance in the experience of OCS. Future research is necessary to delineate specific mechanisms that may account for this relationship. PMID- 26802810 TI - The postmortem proxy-based interview--future directions. AB - The present study aims to provide an overview of the procedural and methodological challenges that need to be addressed when determining the content and application of postmortem proxy-based interviews and recommendations for meeting these challenges in future death investigations are outlined. Preliminary interview considerations are discussed and a step-by-step procedural algorithm for applying proxy-based interview protocol is supplied. A vulnerability-stress model is used for organizing the conceptualization of risk and protective factors into domains of theoretically similar factors. Techniques to improve data collected about mental disorders and stressful life events-variables addressed in nearly all psychological autopsy studies-are suggested, and the importance of examining certain understudied constructs (e.g., psychological factors, family history, select situational factors, childhood adversity, and protective factors) is emphasized. Given the convergence of findings across postmortem proxy-based interviews, whereby extracting postmortem psychiatric diagnoses is the rule, the next generation of studies must offer a point of departure from univariate models, by studying how and why well known exposures interact to produce suicide. In practical terms, targeting specific sub-populations and high-risk individuals can serve as the basis for constructing and testing different clinical hypothesis, which in turn may yield insights into the underlying etiological heterogeneity of suicide. PMID- 26802811 TI - Pro-inflammatory cytokines and psychotherapy in depression: Results from a randomized clinical trial. AB - Depression is a serious condition that is associated with great psychic suffering and major impairments on the patient's general health, quality of life, and social and occupational activities. In some cases, it may lead to suicide. Regardless of the innumerous research works that have already addressed depression in wide and specific facets, there is still a lot to grasp in order to effectively help preventing and treating depression. This work presents data from a randomized clinical trial that sought to evaluate the effectiveness of two brief psychotherapeutic for Depression: Cognitive Behavioral Therapy (CBT) and Supportive-Expressive Dynamic Psychotherapy (SEDP). This was a convenience sample composed of 46 individuals that were evaluated using a structured diagnostic interview and then randomly allocated to the SEDP group. We examined baseline and post-intervention serum levels of the Interleukin-6 (IL-6) and the Tumor Necrosis Factor (TNF-alpha) in addition to the severity of depressive symptoms according to the Outcome Questionnaire - 45.2 (OQ-45.2) and the Beck Depression Inventory (BDI). Results show that serum IL-6 and TNF-alpha levels, as well as the scores from the OQ-45.2 and the BDI significantly decreased after 16 sessions of SEDP (p < 0.001), except for the Interpersonal Relationship domain from the OQ-45. Despite the reduction of serum cytokines levels and OQ-45 and BDI scores, they were only significantly correlated regarding the social role domain from the OQ 45. Nonetheless, our data suggests an effective role of brief psychodynamic psychotherapy in the reduction of depressive symptoms and serum inflammatory levels that are associated with depression. PMID- 26802813 TI - Irreducible tongue-type calcaneal fracture due to interposition of flexor hallucis longus. AB - We present a rare case of interposition of the flexor hallucis longus (FHL) tendon blocking percutaneous closed reduction of a displaced tongue-type calcaneal fracture, and necessitating open repositioning of the tendon and internal fixation through a single extensile lateral approach. Although not recognized until during surgery, with a high index of suspicion, preoperative diagnosis of this injury combination should be possible on high resolution CT, thus enabling better planning of the procedure. The presence of a small sustentacular fragment, especially if markedly displaced or rotated, should further alert the physician as to increased likelihood of such tendon entrapment within the fracture. In the literature, fracture fixation and extrication of the FHL tendon have been performed via either or both lateral and medial approaches. A medial approach may prove necessary when there is severe displacement or rotation of the sustentacular fragment. Arthroscopically assisted surgery may aid in disengaging the tendon from within the fracture site. PMID- 26802814 TI - The safety of the posterior ankle arthroscopy in management of posterior ankle impingement: A cadaveric study. AB - BACKGROUND: Arthroscopic management of the posterior ankle impingement with the patient in supine position has the advantage of dealing with anterior ankle pathology at the same time without the need to change position of the patient. This study aims at evaluation of the safety of portal establishment and instrumentation of this technique. METHODS: Sixteen fresh-frozen cadaver specimens were used. The relationships of the posteromedial and posterolateral portals to the adjacent tendons and nerves and the relationship of the coaxial portal tract with the posterior ankle capsule and the flexor hallucis longus tendon were studied. RESULT: Angle theta1 between the intermalleolar line and the posterior ankle coaxial portal tract averaged 1 degrees (-10 degrees to 22 degrees ). Angle theta2 between the intermalleolar line and the metal rod where the neurovascular bundle started to move averaged 19 degrees (10 degrees to 30 degrees ). Angle theta3 between the intermalleolar line and the metal rod where it reached the lateral border of the Achilles tendon was larger than angle theta2 in all specimens. The angle of safety (thetas) averaged 18 degrees (-1 degrees to 26 degrees ). CONCLUSIONS: Injury to the tendon, nerves or vessels is possible during establishment of the portals and resection of the os trigonum. PMID- 26802815 TI - Metatarsal leiomyosarcoma masquerading as acute osteomyelitis - A diagnostic trap unveiled by vigilant clinical, radiologic and pathologic analysis. AB - Due to overlapping clinical and radiological features, the differentiation between osteomyelitis and bone tumor can be challenging. A 48-year-old lady presented with intermittent left foot pain for a few months. Plain radiographs showed an osteolytic lesion affecting the proximal diaphysis of the left fourth metatarsal bone, with thinning and irregularities of the cortex and focal periosteal reaction. Ultrasonography revealed diffuse subcutaneous edema in the dorsum of the left foot, cortical irregularities along the mid-shaft of the left fourth metatarsal bone, and surrounding periosteal collection. Computed tomography showed medullary expansion along the shaft and base of the left fourth metatarsal bone with cortical irregularities and defects suggestive of cloaca, and focal mild periosteal new bone formation. The clinico-radiologic diagnosis was acute osteomyelitis with periosteal collection. During open biopsy, the finding of intramedullary fleshy tissue in the absence of significant inflammatory edema and purulent discharge, and subsequent negative culture result prompted a review of the histologic slides which was initially reported as benign fibroblastic tissue proliferation. Careful analysis of the histomorphology disclosed a spindle cell sarcoma for which ray amputation of the fourth and fifth metatarsal was performed. The final diagnosis was grade 1 leiomyosarcoma and the patient remained well 33 months after the operation. PMID- 26802812 TI - Omega-3 polyunsaturated fatty acid supplementation and white matter changes in major depression. AB - White matter abnormalities are implicated in major depressive disorder (MDD). As omega-3 polyunsaturated fatty acids (PUFAs) are low in MDD and affect myelination, we hypothesized that PUFA supplementation may alleviate depression through improving white matter integrity. Acutely depressed MDD patients (n = 16) and healthy volunteers (HV, n = 12) had 25-direction diffusion tensor imaging before and after 6 weeks of fish oil supplementation. Plasma phospholipid omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and omega-6 PUFA arachidonic acid (AA) levels were determined before and after supplementation using high-throughput extraction and gas chromatography and expressed as a percentage of total phospholipids (PUFA%). Fractional anisotropy (FA) was computed using a least-squares-fit diffusion tensor with non-linear optimization. Regression analyses were performed with changes in PUFA levels or Hamilton Depression Rating Scale scores as predictors, voxel-wise difference maps of FA as outcome, covariates age and sex, with family-wise correction for multiple comparisons. Increases in plasma phospholipid DHA% (but not EPA% or AA%) after fish oil predicted increases in FA in MDD but not HV, in a cluster including genu and body of the corpus callosum, and anterior corona radiata and cingulum (cluster-level p < 0.001, peak t-score = 8.10, p = 0.002). There was a trend for greater change in FA in MDD responders over nonresponders (t = -1.874, df = 13.56, p = 0.08). Decreased depression severity predicted increased FA in left corticospinal tract and superior longitudinal fasciculus (cluster-level p < 0.001, peak t-score = 5.04, p = 0.0001). Increased FA correlated with increased DHA% and decreased depression severity after fish oil supplementation suggests therapeutic effects of omega-3 PUFAs may be related to improvements in white matter integrity. PMID- 26802816 TI - What is the role of routine ECG screening in stable coronary heart disease and effects of oral anticoagulant, antiarrhythmics in these patients with atrial fibrillation? PMID- 26802817 TI - May hypomagnesaemia; caused by proton pump inhibitor; increase atrial fibrillation risk? PMID- 26802818 TI - A case of apical hypertrophic cardiomyopathy presenting as acute coronary syndrome. PMID- 26802819 TI - A case of atrioventricular nodal reentrant tachycardia associated with arrhythmogenic cardiomyopathy. PMID- 26802820 TI - Determinants of survival and hospitalization in older, heart failure patients receiving home healthcare. AB - INTRODUCTION: Since reported evidence is both scarce and controversial, the objective of this study is to determine the risk factors involved in the prognosis of older patients with heart failure (HF) receiving home healthcare from primary care professionals. METHODS: Retrospective cohort community study was carried out in 52 primary healthcare centers in Barcelona (Spain). A follow up was performed between January 2009 and December 2012 with 7461 HF patients aged >64years. Information was obtained from primary care electronic medical records containing clinical data, functional and cognitive status, total mortality, and hospital admissions for cardiovascular events. RESULTS: Mortality and hospitalization during follow-up were higher in older, HF patients who received home healthcare than those who did not (HR 1.39, 95% CI 1.22-1.58 and 1.92 95% CI 1.72-2.14, respectively). The most relevant determinants for mortality were male gender (HR 1.40, 95%CI 1.10-1.79), previous hospital admission for HF (HR 1.29 95%CI 1.05-1.60), and severe dependence in activities for daily living (ADL) (HR 1.33, 95%CI 1.06-1.67). In contrast, severely dependent ADL patients were not more frequently hospitalized as a consequence of cardiovascular events (0.97, 95% CI 0.77-1.23). CONCLUSIONS: Due to their greater comorbidity and age, mortality and hospitalization in patients requiring home healthcare were higher than those who did not. Among the HF patients receiving home care, mortality and hospital admissions were higher in men, older patients, and in those previously hospitalized for HF. Severe dependence in ADL determined a higher mortality but was not related to increased hospital admission rates. PMID- 26802821 TI - An interventricular and right intraventricular dyssynchrony related to right bundle branch block appearance as cause of RVOT gradient decrease in a HCM patient. PMID- 26802822 TI - The successful management of early rupture of abdominal aortic aneurysm with endovascular stenting and instent stenting for endoleak following EVAR; a case report. PMID- 26802824 TI - The effect of meditative movement on sleep quality: A systematic review. AB - The purpose of this systematic review was to identify and assess evidence related to the efficacy of meditative movement (MM) on sleep quality. We conducted a comprehensive review of relevant studies drawn from English and Chinese databases. Only randomized controlled trials (RCTs) reporting outcomes of the effects of MM (tai chi, qi gong, and yoga) on sleep quality were taken into consideration. Twenty-seven RCTs fulfilled our inclusion criteria and formed the basis for this review. Due to clinical heterogeneity, no meta-analysis was performed. Seventeen studies received a Jadad score of >=3 and were considered high-quality studies. Findings of the 17 studies showed that MM has beneficial effects for various populations on a range of sleep measures. Improvement in sleep quality was reported in the majority of studies and was often accompanied by improvements in quality of life, physical performance, and depression. However, studies to date generally have significant methodological limitations. Additional RCTs with rigorous research designs focusing on sleep quality or insomnia and testing specific hypotheses are needed to clearly establish the efficacy of MM in improving sleep quality and its potential use as an intervention for various populations. PMID- 26802825 TI - Cultivating Future Scholars. PMID- 26802826 TI - HELLP Syndrome and the Effects on the Neonate. AB - HELLP syndrome is most often diagnosed between 27 and 37 weeks gestation. It is also a diagnosis that can be seen during the postpartum period. The effects of HELLP syndrome on the neonate can be significant. Recognizing the risks to the neonate can assist the clinician in preparing for the neonate prior to delivery. In doing so, the mortality and morbidity rates can be reduced. PMID- 26802823 TI - A new view of "dream enactment" in REM sleep behavior disorder. AB - Patients with REM sleep behavior disorder (RBD) exhibit increased muscle tone and exaggerated myoclonic twitching during REM sleep. In addition, violent movements of the limbs, and complex behaviors that can sometimes appear to involve the enactment of dreams, are associated with RBD. These behaviors are widely thought to result from a dysfunction involving atonia-producing neural circuitry in the brainstem, thereby unmasking cortically generated dreams. Here we scrutinize the assumptions that led to this interpretation of RBD. In particular, we challenge the assumption that motor cortex produces twitches during REM sleep, thus calling into question the related assumption that motor cortex is primarily responsible for all of the pathological movements of RBD. Moreover, motor cortex is not even necessary to produce complex behavior; for example, stimulation of some brainstem structures can produce defensive and aggressive behaviors in rats and monkeys that are strikingly similar to those reported in human patients with RBD. Accordingly, we suggest an interpretation of RBD that focuses increased attention on the brainstem as a source of the pathological movements and that considers sensory feedback from moving limbs as an important influence on the content of dream mentation. PMID- 26802827 TI - Congenital Toxoplasmosis: A Review. AB - Acute infection of toxoplasmosis during pregnancy is detrimental to the developing fetus. In the United States, approximately 1 in 10,000 live births are affected by congenital toxoplasmosis. Although multifactorial in etiology, maternal infection is primarily attributed to the consumption of contaminated meat or water. Infection and transmission to the fetus may result in devastating neurologic impairment. Screening methods for all pregnant women should be implemented in routine prenatal care. This article will highlight the inherent dangers of congenital toxoplasmosis, while including general care of the fetus for prevention of transmission, medical management, and long-term outcomes. PMID- 26802828 TI - Herpes Simplex Virus: Beyond the Basics. AB - One of the most common sexually transmitted infections is the herpes simplex virus (HSV) Type 2. Although the incidence of newborn infection is not as common as in adults, approximately 1,500 neonates are diagnosed annually with HSV infection. HSV can be detrimental to the life of a newborn, with morbidity and mortality rates of up to 65 percent. This article addresses the maternal and fetal complications of HSV and the impact of HSV on the newborn along with diagnostic evaluation methods. In addition, treatment options and evidence-based practices regarding HSV are defined. Despite growing technology and medical treatment for early identification of HSV, this virus remains challenging and can deeply impact the life of an infant and his or her family. Early diagnosis, treatment, and intervention of an infant with HSV are crucial to ensure the livelihood of the newborn. PMID- 26802829 TI - Retinopathy of Prematurity: Pathogenesis and Current Treatment Options. AB - Retinopathy of prematurity (ROP) is a vasoproliferative retinal disorder that continues to be the major cause of preventable childhood blindness worldwide. Its incidence is inversely proportional to gestational age and birth weight. Approximately 65 percent of neonates with <1,250 g birth weight and 80 percent of those with 1,000 g birth weight will develop some degree of ROP. ROP can cause mild retinal disease without major visual defects or can adversely progress to retinal detachment and blindness through aggressive vascular proliferation. The purpose of this article is to raise awareness about the history of ROP, pathogenesis, normal retinal vascular development, international classification of ROP, and risk factors. Conventional ROP treatment and the promising antivascular endothelial growth factor monotherapy will also be explored. PMID- 26802830 TI - Quality Appraisal: Part II. AB - Quality appraisal is an essential step in the evidence-based practice process. This column focuses on evaluating the quality of the individual study and its applicability to practice. PMID- 26802831 TI - Neuro-NICUs: Nurturing the Tiniest of Brains. AB - Neuro-NICUs are the latest in NICU programs, with a focus on nurturing tiny brains using the latest in research, technology, and common sense. In this column, we talk with expert Kathi randall, RN, CNS, NNP, who has helped NICUs incorporate this new program into their units. PMID- 26802833 TI - News of the Academy of Neonatal Nursing. PMID- 26802834 TI - Respiratory disease in the Asia-Pacific region: Cough as a key symptom. AB - BACKGROUND: Respiratory diseases represent a significant impact on health care. A cross-sectional, multicountry (India, Korea, Malaysia, Singapore, Taiwan, and Thailand) observational study was conducted to investigate the proportion of adult patients who received care for a primary diagnosis of asthma, allergic rhinitis (AR), chronic obstructive pulmonary disease (COPD), or rhinosinusitis. OBJECTIVE: To determine the proportion of patients who received care for asthma, AR, COPD, and rhinosinusitis, and the frequency and main symptoms reported. METHODS: Patients ages >=18 years, who presented to a physician with symptoms that met the diagnostic criteria for a primary diagnosis of asthma, AR, COPD, or rhinosinusitis were enrolled. Patients and physicians completed a survey that contained questions related to demographics and respiratory symptoms. RESULTS: A total of 13,902 patients with a respiratory disorder were screened, of whom 7030 were eligible and 5250 enrolled. The highest percentage of patients who received care had a primary diagnosis of AR (14.0% [95% confidence interval {CI}, 13.4 14.6%]), followed by asthma (13.5% [95% CI, 12.9-14.1%]), rhinosinusitis (5.4% [95% CI, 4.6-5.3%]), and COPD (4.9% [95% CI, 5.0-5.7%]). Patients with a primary diagnosis of COPD (73%), followed by asthma (61%), rhinosinusitis (59%), and AR (47%) most frequently reported cough as a symptom. Cough was the main reason for seeking medical care among patients with a primary diagnosis of COPD (43%), asthma (33%), rhinosinusitis (13%), and AR (11%). CONCLUSION: Asthma, AR, COPD, and rhinosinusitis represent a significant proportion of respiratory disorders in patients who presented to health care professionals in the Asia-Pacific region, many with concomitant disease. Cough was a prominent symptom and the major reason for patients with respiratory diseases to seek medical care. PMID- 26802836 TI - Evolving Therapeutic Strategies in Mucosal Melanoma Have Not Improved Survival Over Five Decades. AB - Mucosal melanoma represents a distinct minority of disease sites and portends a worse outcome. The ideal treatment and role of adjuvant therapy remains unknown at this time. We hypothesized that a combination of neoadjuvant and adjuvant therapies would improve survival in these aggressive melanomas. Our large, prospectively maintained melanoma database was queried for all patients diagnosed with mucosal melanoma. Over the past five decades, 227 patients were treated for mucosal melanoma. There were 82 patients with anorectal, 75 with sinonasal, and 70 with urogenital melanoma. Five-year overall survival and melanoma-specific survival for the entire cohort were 32.8 and 37.5 per cent, respectively, with median overall survival of 38.7 months. One hundred forty-two patients (63.8%) underwent adjuvant therapy and 15 were treated neoadjuvantly (6.6%). There was no survival difference by therapy type or timing, disease site, or decade of diagnosis. There was improved survival in patients undergoing multiple surgeries (Hazard Ratio [HR] 0.55, P = 0.0005). Patients receiving neoadjuvant therapy had significantly worse survival outcomes (HR 2.49, P = 0.013). Over the past five decades, improvements have not been seen in outcomes for mucosal melanoma. Although multiple surgical interventions portend a better outcome in patients with mucosal melanoma, adjuvant treatment decisions must be individualized. PMID- 26802837 TI - The Uninsured, the Homeless, and the Undocumented Immigrant Trauma Patient. Revealing Health-Care Disparity at a Level 1 Trauma Center. PMID- 26802838 TI - Cost of Hospitalization for Infantile Pyloric Stenosis. PMID- 26802839 TI - Outcomes of 157 V-Patch(TM) Implants in the Repair of Umbilical, Epigastric, and Incisional Hernias. AB - Umbilical, epigastric, and incisional hernias have traditionally been repaired using a Mayo or tensioned suture technique, with recurrence rates of approximately 50 per cent. Recent studies have shown that a tension-free repair using mesh can drastically decrease recurrence rates. Reinforced deployment prostheses are preferred because they enable retrofascial placement through a small incision, thus avoiding the potential morbidity of a larger incision and the costs associated with a laparoscopic approach. A retrospective chart review was performed of all umbilical, epigastric and incisional hernias repaired with V Patch, a reinforced deployment prosthesis, by a single surgeon. Data analysis included patient characteristics, operative and postoperative metrics, hernia recurrence, and complication rates. Between 2009 and 2012, 157 implantations were performed in 152 patients during 156 procedures. Patient age ranged from 20 to 85 (mean 48). There were 88 females (57.9%) and 64 males (42.1%) with average body mass index of 30.6. Patch size distribution was 78 small (49.7%), 55 medium (35.0%), and 24 large (15.3%). There were 81 umbilical hernias (51.6%), 36 epigastric hernias (22.9%), 39 incisional hernias (24.8%), and 1 multiple recurrent inguinal hernia (0.6%) repaired. Follow-up time ranged from 18 months to 4.3 years. There were six hernia recurrences (3.2%). Complications included three patients (1.9%) with mesh infection, one with an enterocutaneous fistula (0.6%), and one patient with a postoperative small bowel obstruction (0.6%). Four patients required patch explantation (2.5%). The V-Patch reinforced deployment prosthesis is effective in the treatment of umbilical, epigastric, and incisional hernias, and has a low rate of complications. PMID- 26802840 TI - Assessing the Night Float Educational Experience. PMID- 26802842 TI - A Decade of Duty Hour Standards: Increasing Pass Rate Trends on the American Board of Plastic Surgery Written Examination. PMID- 26802841 TI - A Systematic Review of Perforated Appendicitis and Phlegmon: Interval Appendectomy or Wait-and-See? AB - Patients with appendiceal abscess or phlegmon have been traditionally managed with antibiotics and radiologically guided drainage of the abscess. Many studies have questioned the need for interval appendectomy. A systematic review of the nonsurgical treatment of patients with an appendiceal abscess or phlegmon was undertaken. The rate of recurrence after nonsurgical management, morbidity and length of hospital stay was measured. PubMed and Cochrane databases were queried to identify 21 studies reporting the morbidity of nonsurgical treatment of appendiceal phlegmon or abscess, and five studies reporting the morbidity of performing interval appendectomy. Repeat nonsurgical management was compared with that of performing interval appendectomy. The studies included a total of 1943 patients, of which 1400 patients were managed nonsurgically and 543 patients underwent interval appendectomy. Nonoperative treatment had a mean recurrence of 12.4 per cent, a morbidity of 13.3 per cent, and the length of hospital stay was 9.6 days. The mean morbidity rate and length of hospital stay for patients who underwent interval appendectomy was 10.4 per cent and 5.0 days, respectively. Interval appendectomy and repeat nonoperative management in case of recurrence are associated with similar morbidity; however, elective interval appendectomy implies additional operative costs to prevent recurrence in one of eight patients. PMID- 26802843 TI - Load Sharing, not Load Bearing Plates: Lessons Learned from Failure of Rib Fracture Stabilization. PMID- 26802844 TI - Pancreatectomy in Patients with Impaired Renal Function: How Risky Is It? AB - Chronic renal impairment causes profound physiologic and metabolic changes. Its impact on surgical outcome after pancreatectomy is not well established. We sought to quantify complication rates of pancreatectomy in patients with chronic renal impairment. Database from the American College of Surgeons National Surgical Quality Improvement Project (2005-2011) was queried to identify patients with chronic renal impairment who underwent pancreatectomy. The study population consisted of 16,708 patients of whom 16,649 patients were not on dialysis and 59 patients were on dialysis. Overall mortality for those on dialysis was 5.1 per cent, whereas it was 2.3 per cent for those not on dialysis (P = 0.114). Patients on dialysis were more likely to have failure to wean ventilation (P < 0.001), reintubation (P = 0.004), myocardial infarction (P = 0.007), and sepsis (P = 0.046). Patients not on dialysis were then divided into three groups: serum creatinine levels <1.2 mg/dL, between 1.2 mg/dL and 2.0 mg/dL, and >2.0 mg/dL. We found the mortality rates for these three groups were 2.0 per cent, 4.6 per cent, and 7.5 per cent, respectively (P < 0.001). In conclusion, need for dialysis is associated with increased postoperative complications. Increased serum creatinine levels were associated with increased mortality rates. These findings should facilitate informative risk/benefit calculation for patients with renal impairment who are considering pancreatectomy. PMID- 26802845 TI - Transabdominal Preperitoneal Repair of Spigelian Hernia. PMID- 26802846 TI - Surgical Care Improvement Project Measures among Rural and Urban Hospitals in West Virginia. PMID- 26802847 TI - The Charlson Comorbidity Index (CCI) as a Mortality Predictor after Surgery in Elderly Patients. AB - The increasing range of surgery in elderly patients reflects the changing demography where in the next 10 years one quarter of the population will be 65 years of age or older. There is presently no consensus concerning the optimal predictive markers for postoperative morbidity and mortality after surgery in older patients with an appreciation that physical frailty is more important than chronological age. In this retrospective analysis, we have compared the impact of age and the calculated preoperative Charlson Comorbidity Index (CCI) on early (30 day) and late (one-year) mortality in a group of patients >75 years of age dividing them into an "older old" cohort (75-84 years of age, Group A) and an "oldest old" group (>=85 years of age, Group B). Increased age was associated with a higher death rate after emergency surgery, with late deaths after elective surgery exceeding those after emergency operations. A higher mean CCI was noted in both age groups in early nonsurvivors after both elective and emergency surgery with a more significant effect of the preoperative CCI than chronological age for the prediction of late postoperative death for both groups after elective and emergency operations. Although the CCI was not designed to predict perioperative mortality in surgical cohorts, it correlates with a greater risk than age for perioperative death in the elderly. PMID- 26802848 TI - Successful Treatment of Acute Vein Graft Thrombosis Precipitated by Delayed Sepsis and Duodenocaval Fistulization. PMID- 26802849 TI - Does the Insurance Status Predict the Outcome of the Trauma Patients with Abdominal Gunshot Wounds? Report from a Level I Trauma Academic Center with a Public Hospital. PMID- 26802850 TI - Do Radiographic Findings of Gangrenous Cholecystitis in the Preoperative Setting Influence Patient Outcome? PMID- 26802851 TI - Measuring Patterns of Surgeon Confidence Using a Novel Assessment Tool. AB - Confidence should increase during surgical training and practice. However, few data exist regarding confidence of surgeons across this continuum. Confidence may develop differently in clinical and personal domains, or may erode as specialization or age restricts practice. A reliable scale of confidence is needed to track this competency. A novel survey was distributed to surgeons in private and academic settings. One hundred and thirty-four respondents completed this cross-sectional survey. Surgeons reported anticipated reactions to clinical scenarios within three patient care domains (acute inpatient, nonacute inpatient, and outpatient) and in personal spheres. Confidence scores were plotted against years of experience. Curves of best fit were generated and trends assessed. A subgroup completed a second survey after four years to assess the survey's reliability over time. During residency, there is steep improvement in confidence reported by surgeons in all clinical domains, with further increase for inpatient domains during transition into practice. Confidence in personal spheres also increases quickly during residency and thereafter. The surgeon confidence scale captures the expected acquisition of confidence during early surgical experience, and will have value in following trends in surgeon confidence as training and practice patterns change. PMID- 26802852 TI - Delayed Presentation of Cardiac Injury after a Penetrating Stab Wound to the Chest. PMID- 26802853 TI - Management of Acquired Tracheoesophageal Fistula Complicating Endoscopic Management for Corrosive Esophageal Stricture. PMID- 26802854 TI - Golf Cart-related Injuries: A Community at Risk. PMID- 26802855 TI - Delineation of Criteria for Admission to Step Down in the Mild Traumatic Brain Injury Patient. AB - Patients that suffer a mild traumatic brain injury (TBI) with intracranial hemorrhage are commonly admitted to an intensive care unit with repeat imaging in 12 to 24 hours. This is costly to the health-care system. This study aimed to evaluate this practice and to identify criteria to triage patients to lower levels of monitored care. A retrospective review was performed at a university based Level I trauma center. Patients with mild TBI were included. Data were collected on demographics, neurological status at 6, 12, and 24 hours, CT scan results, and medical or surgical interventions were required. A total of 389 patients were evaluated, 53 had a documented neurological decline while being admitted. Factors found to be associated with a neurological decline included Glasgow Coma Scale (GCS) < 15 (P = 0.002), age greater than 55 (P < 0.001), and warfarin use (P = 0.039). Aspirin and Plavix were not associated with neurological decline. No patient age <55 with a GCS of 15 had a documented decline. Several risk factors were found to be associated with neurological decline after mild TBI. These include age, GCS < 15, and warfarin use. Patients aged <55 with GCS 15, posed minimal risk for deterioration. Patients aged <55 and with a GCS of 15 can be admitted to a monitored step-down bed with less frequent neurological checks. PMID- 26802856 TI - CT Chest with IV Contrast Compared with CT Angiography after Blunt Trauma. AB - Blunt aortic injury (BAI) after chest trauma is a potentially lethal condition. Rapid diagnosis is important to appropriately treat patients. The purpose of this study was to compare CT with intravenous contrast (CTI) to CT with angiography (CTA) in the initial evaluation of blunt chest trauma patients. This was a retrospective review of all blunt trauma patients who received a CTI or CTA during the initial evaluation at an urban Level I trauma center from January 1, 2010 to December 31, 2013. Two-hundred and eighty-one trauma patients met inclusion criteria. Most, 167/281 (59%) received CTI and 114/281 (41%) received CTA. There were no differences between cohorts in age, gender, initial heart rate, systolic blood pressure, and Glasgow Coma Scale in emergency department. Mortality rates were similar for CTI and CTA (4% vs 8%, P = 0.20). CTI identified an injury in 54 per cent compared with 46 per cent in CTA (P = 0.05). Overall, 2 per cent of patients had BAI with similar rates in CTI and CTA (2% vs 2%, P = 0.80). BAI was not missed using either CTI or CTA. Trauma patients studied with CTI had similar diagnostic findings as CTA. CTI may be preferable to CTA during the initial assessment for possible BAI because of a single contrast injection for whole body CT. PMID- 26802857 TI - Reduction of Costs for Pelvic Exenteration Performed by High Volume Surgeons: Analysis of the Maryland Health Service Cost Review Commission Database. AB - High volume hospitals (HVHs) and high volume surgeons (HVSs) have better outcomes after complex procedures, but the association between surgeon and hospital volumes and patient outcomes is not completely understood. Our aim was to evaluate the impact of surgeon and hospital volumes, and their interaction, on postoperative outcomes and costs in patients undergoing pelvic exenteration (PE) in the state of Maryland. A review of the Maryland Health Services Cost Review Commission database between 2000 and 2011 was performed. Patients were compared for demographics and clinical variables. The differences in length of hospital stay , length of intensive care unit (ICU) stay, operating room (OR) cost, and total cost were compared for surgeon volume and hospital volume controlling for all other factors. Surgery performed by HVS at HVH had the shortest ICU stay and lowest OR cost. When PE was performed by a low volume surgeon at an HVH, the OR cost and total cost were the highest and increased by $2,683 (P < 0.0001) and $16,076 (P < 0.0001), respectively. OR costs reduced when surgery was performed by an HVS at an HVH ($-1632, P = 0.008). PE performed by HVS at HVH is significantly associated with lower OR costs and ICU stay. We feel this is indicative of lower complication rates and higher quality care. PMID- 26802858 TI - Widespread Implications of ACOSOG Z0011: Effect on Total Mastectomy Patients. AB - The ACOSOG Z0011 trial demonstrated that axillary lymph node dissection (ALND) is not necessary for all breast cancer patients. Patients who underwent breast conservation surgery (BCS) or total mastectomy (TM) and met Z0011 criteria were identified and sorted into pre- and post- Z0011 cohorts. Four hundred ninety four patients had breast cancer surgery from July 2008 to February 2013. Of these, 255 were pre-Z0011 and 239 were post. Pre-Z0011, 14 patients met Z0011 inclusion criteria in BCS subgroup. ALND was performed in 10 of these patients (71%). Post Z0011, 14 patients met inclusion criteria, only 1 received ALND (7%). The decrease in ALND rate was significant (p=0.001). Pre-Z0011, 28 patients in TM subgroup met extrapolated inclusion criteria, twenty-three of which received ALND (82%). Post-Z0011, 14 patients in TM subgroup met extrapolated criteria, five of which underwent ALND (36%). The decrease in rate of ALND was significant (p=0.005). This study demonstrates that the Z0011 trial significantly altered management of the axilla in all breast cancer patients with positive sentinel lymph nodes, not just those receiving BCS. PMID- 26802859 TI - Using a Checklist to Improve Family Communication in Trauma Care. AB - Modern concepts of patient-centered care emphasize effective communication with patients and families, an essential requirement in acute trauma settings. We hypothesized that using a checklist to guide the initial family conversation would improve the family's perception of the interaction. Institutional Review Board-approved, prospective pre/post study involving families of trauma patients admitted to our Level I trauma center for >24 hours. In the control group, families received information according to existing practices. In the study group, residents gave patient information to a first-degree family member using a checklist that guided the interaction. The checklist included a physician introduction, patient condition, list of known injuries, admission unit or intensive care unit, any consultants involved, plans for additional studies or operations, and opportunity for family to ask questions. An 11-item survey was administered 24 to 48 hours after admission to each group that evaluated the trauma team's communication in the areas of physician introduction, patient condition, ongoing treatment, and family perception of the interaction. Responses were on a Likert scale and analyzed using the Wilcoxon-Mann-Whitney test. There were 130 patients in each group. The study group had significantly (P < 0.05) better responses in 8 of 11 items surveyed: physician spoke to family, physician introduction, understanding of their relative's injuries, admitting unit, consultants involved, urgent surgical procedures required, ongoing diagnostic studies, and understanding of the treatment plan. In conclusion, using a checklist improves the perception of the initial communication between the trauma team and family members of trauma patients, especially their understanding of the treatment plan. PMID- 26802860 TI - Appendectomy: Should it Be Performed So Quickly? AB - Controversy surrounds appendectomy timings and their effects on postoperative outcomes. This study evaluated the influence of hospital delays on perforation rates and complications in patients with acute appendicitis. From January 2008 to December 2013, the cases of 4148 consecutive patients who had undergone appendectomies for suspected appendicitis were reviewed. The patients' demographic data, times from symptom onset to hospital arrival (prehospital delay), times from hospital arrival to surgery (hospital delay), histological findings, and postoperative outcomes were documented. Perforation rates and complications were assessed at each time interval between symptom onset and surgery. Perforation rates and complications increased with longer prehospital delays, but no correlations were evident between hospital delays and perforation rates or between hospital delays and complications. Although delaying appendectomies for >18 hours had no statistically significant impact on perforation rates (25.3 vs 19.4%, P = 0.133), it caused more complications (8.7 vs 3.8%, P = 0.023) compared with cases delayed for 12 to 18 hours. Multivariate analyses determined that hospital delays were not associated with increased risks of perforation, complications, wound infections, or intra-abdominal abscesses. However, a >18-hour hospital delay was associated with a significantly increased risk of postoperative ileus (odds ratio = 2.94, 95% confidence interval = 1.17 7.41, P = 0.022). Hospital delays were not associated with significantly increased risks of perforation and complications. However, patients with perforated appendicitis had higher risks of developing postoperative ileus if hospital delays were >18 hours. Therefore, hospital delays of <=18 hours are safe, but caution is required if delays are >18 hours. PMID- 26802861 TI - Posttraumatic Resuscitation Affects Stent Graft Sizing in Patients with Blunt Thoracic Aortic Injury. AB - Patients with blunt aortic injury often present to the emergency department in a relatively hypovolemic state. These patients undergo extensive inhospital resuscitation. The effect of posttraumatic resuscitation on aortic diameter has implications for stent graft sizing. The potential utility of repeat aortic imaging after resuscitation remains unclear. A retrospective chart review of all adult patients presenting to a Level I trauma center between the years 2007 and 2013 was performed. Fifty-three patients were identified with a diagnosis of traumatic aortic injury. Of those, 10 had 2 CT scans before aortic repair and were selected as the study population for analysis. After resuscitation, there was a significant increase in aortic diameter both proximal and distal to the aortic injury: proximal aortic diameter increase of 1.97 mm and distal aortic diameter increase of 1.48 mm. This retrospective study shows that after resuscitation, there is a significant increase in proximal and distal aortic diameter. Interval reimaging of the thoracic aorta may be beneficial after adequate stabilization of the patient's other injuries. In certain cases, more appropriate sizing may prevent a device-related complication. PMID- 26802862 TI - Implementation of an Acute Care Surgery Service in a Community Hospital: Impact on Hospital Efficiency and Patient Outcomes. AB - A service led by acute care surgeons managing trauma, critically ill surgical, and emergency general surgery patients via an acute care surgery model of patient care improves hospital efficiency and patient outcomes at university-affiliated hospitals and American College of Surgeons-verified trauma centers. Our goal was to determine whether an acute care surgeon led service, entitled the Surgical Trauma and Acute Resuscitative Service (STARS) that implemented an acute care surgery model of patient care, could improve hospital efficiency and patient outcomes at a community hospital. A total of 492 patient charts were reviewed, which included 230 before the implementation of the STARS [pre-STARS (control)] and 262 after the implementation of the STARS [post-STARS (study)]. Demographics included age, gender, Acute Physiology and Chronic Health Evaluation 2 score, and medical comorbidities. Efficiency data included length of stay in emergency department (ED-LOS), length of stay in surgical intensive care unit (SICU-LOS), and length of stay in hospital (H-LOS), and total in hospital charges. Average age was 64.1 + 16.4 years, 255 males (51.83%) and 237 females (48.17%). Average Acute Physiology and Chronic Health Evaluation 2 score was 11.9 + 5.8. No significant differences in demographics were observed. Average decreases in ED LOS (9.7 + 9.6 hours, pre-STARS versus 6.6 + 4.5 hours, post-STARS), SICU-LOS (5.3 + 9.6 days, pre-STARS versus 3.5 + 4.8 days, post-STARS), H-LOS (12.4 + 12.7 days, pre-STARS versus 11.4 + 11.3 days, post-STARS), and total in hospital charges ($419,602.6 + $519,523.0 pre-STARS to $374,816.7 + $411,935.8 post-STARS) post-STARS. Regression analysis revealed decreased ED-LOS-2.9 hours [P = 0.17; 95% confidence interval (CI): -7.0, 1.2], SICU-LOS-6.3 days (P < 0.001; 95% CI: 9.3, -3.2), H-LOS-7.6 days (P = 0.001; 95% CI: -12.1, -3.1), and 3.4 times greater odds of survival (P = 0.04; 95% CI: 1.1, 10.7) post-STARS. In conclusion, implementation of the STARS improved hospital efficiency and patient outcomes at a community hospital. PMID- 26802863 TI - Restrictive Transfusion in Geriatric Trauma Patients. AB - To determine whether a restrictive strategy of red cell transfusion was safe in elderly trauma patients, we compared those treated with a restrictive transfusion strategy versus those who were liberally transfused. We performed a retrospective study of elderly (age >= 70 years) trauma patients admitted to our Level I trauma center from 2005 to 2013. Patients with a hemoglobin (Hg) < 10 g/dL after 48 hours were included. We excluded patients with an Injury Severity Score > 25 or active cardiac ischemia. Patients who were transfused for an Hg < 10 g/dL (liberal group) were compared to those who were transfused for an Hg< 7 g/dL (restrictive group). There were 382 patients included, 229 and 153 in the liberal and restrictive transfusion groups, respectively. All patients in the liberal group and 20 per cent of patients in the restrictive group received a transfusion (P < 0.0001). Patients in the liberal group had more overall complications (52 vs 32%, P = 0.0001). On multivariate analysis, receiving a transfusion was an independent risk factor to develop a complication [odds ratio = 2.3 (1.5-3.6), P < 0.0001]. For survivors, patients in the liberal group spent more days in the hospital (nine versus seven days, P = 0.007) and intensive care unit (two versus one day, P = 0.01). There was no difference in mortality (3 vs 4%, P = 0.82). In conclusion, restrictive transfusion appears to be safe in elderly trauma patients and may be associated with decreased complications and shortened length of stay. PMID- 26802864 TI - E-cigarette regulation and policy: UK vapers' perspectives. AB - BACKGROUND AND AIMS: The rapid increase in use of electronic cigarettes (e cigarettes) has created an international policy dilemma concerning how to use these products. This study assesses the types of beliefs that e-cigarette users in the United Kingdom may hold concerning regulation. DESIGN: Qualitative thematic analysis of written answers to open-ended questions. SETTING: United Kingdom, questionnaire conducted by post, 44% recruited from online forums and 56% non-online. PARTICIPANTS: Fifty-five UK vapers, 55% male, mean age 46 years, 84% sole users of e-cigarettes, 95% vaping daily. MEASUREMENTS: Open-ended questions on regulatory and policy options. FINDINGS: 'Protecting youth' was seen as a fundamental regulatory requirement which should be achieved through childproofing, age limits, no advertising aimed at children and health warnings about addictiveness of nicotine, but not the restriction of flavours. There was little support for regulating e-cigarettes as medicines or limiting the strength of nicotine liquids. In terms of public use, participants argued against a blanket ban on public vaping given perceptions of a lack of scientific evidence of harm. However, they supported the principle of autonomy, that individuals and organizations have the right to restrict vaping. Some participants suggested banning vaping in places such as schools, hospitals or around food, in line with current smoking norms. Vapers' regulatory positions were accompanied by political concerns about the use (and misuse) of scientific evidence. CONCLUSIONS: With regard to regulation of e-cigarettes, issues that are salient to UK vapers may include the need for youth protection, regulation as medicines, strength of e liquids, bans on public vaping and concerns about the misuse of scientific evidence. PMID- 26802865 TI - Reliable Intraoperative Repair Nuances of Cerebrospinal Fluid Leak in Anterior Cervical Spine Surgery and Review of the Literature. AB - BACKGROUND: Cerebrospinal fluid (CSF) leak during anterior cervical spine surgery can lead to complications, including wound breakdown, meningitis, headaches, need for lumbar drain, or additional surgery. These leaks can be difficult to manage given the limited field of view and lack of deep access. Herein, we describe 8 consecutive patients who underwent intraoperative repair of CSF leak, with no postoperative evidence of wound dehiscence or drainage. METHODS: A retrospective review was performed on 8 cases where CSF leak was encountered during an anterior cervical spine surgery. Patients had ossification of the posterior longitudinal ligament, intradural disk herniation, or dural ectasia. Intraoperative repair was as follows. First, CSF was drained to low pressure, and durotomy was covered by dural substitute and sealant agent. Then the interbody graft used was manually undersized in the anteroposterior dimension to allow for expansion of the agents used. Anterior instrumentation was then performed. Finally, a wound drain was anchored to a biologic bag for shoulder level passive drainage. RESULTS: In all 8 cases, there were no cases of wound dehiscence or CSF leak using this strategy. Likewise, there was no evidence of cord compression or neurologic deficits. No meningitis or persistent headaches were reported, and there was no need for lumbar drain placement at any time postoperatively. CONCLUSIONS: Once durotomy is encountered during anterior spine surgery, draining the CSF to a low pressure followed by dural substitute with a sealing agent, followed by a smaller anteroposterior size graft is an effective strategy of preventing complications in an inescapable problem. PMID- 26802866 TI - Results of Spinal Fusion After Spinal Nerve Sheath Tumor Resection. AB - INTRODUCTION: Intradural extramedullary spine tumors, approximately one-half of which are peripheral nerve sheath tumors (PNSTs), comprise two-thirds of primary spinal neoplasms. Given the rarity of PNSTs and the restricted indications for adding fusion to laminectomy for tumor resection, analyses of spinal fusion outcomes are limited. METHODS: Demographics, clinical presentation, tumor characteristics, extent of resection, spinal fusion, complications, and clinical follow-up were recorded retrospectively. RESULTS: A total of 221 tumors in 199 patients were identified (53 neurofibromas, 163 schwannomas, 5 malignant PNSTs); 78 patients underwent fusion (70 instrumented; 8 noninstrumented). Fusion rates were higher for extradural versus intradural lesions (60% vs. 29%; P = 0.001) and for tumors involving the cervicothoracic junction (88% vs. 31%, P < 0.001). There was no difference in fusion rates based on pathology. Rates of new or worsening sensory (19% in fusion vs. 13% in nonfused) or motor deficits (8% in fused vs. 4% in nonfused), wound infection (3% in fused vs. 6% in nonfused) and cerebrospinal fluid (CSF) leak or pseudomeningocele (6% in fused vs. 4% in nonfused) were not statistically different. There were 10 fusion-related complications: 6 adjacent segment disease, 3 implant failures, and 1 pseudoarthrosis. Mean time from surgery to last follow-up was 32 months. CONCLUSIONS: In this cohort, PNSTs in the cervical spine, spanning the cervicothoracic junction, and extradural tumors were associated with higher rates of spinal fusion. Fusion was not associated with new or worsening motor/sensory deficits, CSF leak, pseudomeningocele, wound infection, or spinal deformity. Overall, spinal fusions were well tolerated and did not increase the risk of postoperative complications. PMID- 26802867 TI - Isolated Cortical Venous Thrombosis as a Mimic for Cortical Subarachnoid Hemorrhage. AB - Isolated cortical venous thrombosis is very rare and poorly understood. The clinical presentation is also not well described in the literature. We report here a case of isolated cortical venous thrombosis that mimicked cortical subarachnoid hemorrhage (SAH). A 62-year-old man with a history of chronic subdural hemorrhage visited our hospital with headache. Brain computed tomography (CT) revealed a linear hyperdense area in the right central sulcus (cord sign), suggestive of isolated cortical SAH. Magnetic resonance imaging (MRI) revealed susceptibility in the corresponding area. CT angiography revealed no specific finding. However, transfemoral cerebral angiography (TFCA) identified filling defects in the right cortical veins. Under isolated cortical venous thrombosis, anticoagulation therapy was used to prevent the propagation of thrombosis. The patient had no recurrence of symptoms. If a cord sign is present on noncontrast CT images, further studies (MRI/magnetic resonance venography or TFCA) should be performed in a step-wise manner. Such considerations could prevent a fatal outcome and poor prognosis. PMID- 26802868 TI - Bilateral Pallidotomy for Cervical Dystonia After Failed Selective Peripheral Denervation. AB - BACKGROUND: We investigated the utility of pallidotomy for cervical dystonia after failed selective peripheral denervation. CASE DESCRIPTION: A 36-year-old man presented with cervical dystonia with limited range of motion of the left shoulder, particularly in abduction. His Tsui score was 8. Owing to the ineffectiveness of botulinum toxin injection, he underwent selective peripheral denervation with an unsatisfactory outcome, with a postoperative Tsui score of 6. Simultaneous bilateral pallidotomy was performed with local anesthesia 1 year after the initial surgery. The day after the pallidotomy, all dystonic symptoms were markedly improved except for the limited range of shoulder abduction. The Tsui score recorded 1 week after the pallidotomy was 1. Transient aggressive behavior was the only postoperative complication. During clinical follow-up period of 1 year, no recurrence of the symptoms was observed. CONCLUSIONS: Pallidotomy represents a feasible and effective treatment for cervical dystonia refractory to selective peripheral denervation without hardware-related complications. PMID- 26802869 TI - Low-Cost Fluorescein Detection System for High-Grade Glioma Surgery. AB - BACKGROUND: Intraoperative fluorescein detection has been used in the fields of vascular and oncologic neurosurgery since 1948. Modifications of the optics in order to enhance the fluorescence contrast under microscopic view have been developed by many authors. The industries, during the past 10 years, provided commercial high-cost optimized apparatuses. Reviewing the literature, we found that the prototypical techniques were definitely inexpensive but lacked reliability, reproducibility, and standard legal norms. METHODS: We describe the developing of a fluorescein detection system that could be economic, simple, effective, and law abiding. RESULTS: We employed a commercial violet-blue filter designed for fluorescein excitation in endoscopic procedures and used commercial photographic yellow optical filters for fluorescence detection. All the instrumentation is cleared for clinical use, and its cost is up to 200 times lower than commercial apparatuses. CONCLUSION: Our results show a good distinction of fluorescein-stained structures, with overall acceptable operating light conditions. PMID- 26802870 TI - Hybrid Operating Room for Combined Neuroendovascular and Endoscopic Treatment of Ruptured Cerebral Aneurysms with Intraventricular Hemorrhage. AB - BACKGROUND: Intraventricular hemorrhages (IVHs) caused by ruptured cerebral aneurysms often have poor outcomes. Treatment challenges include comorbidities, increased intracranial pressure caused by IVH, and risk of rebleeding. CASE DESCRIPTION: Two cases of severe IVH accompanied by acute hydrocephalus caused by ruptured aneurysm were treated with coil embolization followed by endoscopic hematoma evacuation as a single treatment session in a hybrid operating room (OR) equipped with a multipurpose angio biplane system. The first case was an 84-year old woman with a ruptured basilar top aneurysm, who presented with Hunt and Hess (H&H) grade 5 subarachnoid hemorrhage (SAH) with packed IVH. The second case was a 43-year-old man with a ruptured anterior communicating artery aneurysm who presented with H&H grade 5 SAH with packed IVH. In both cases, endovascular coil embolization was performed first to prevent intraoperative bleeding. The coiled aneurysms suddenly appeared on the screen of the endoscope during the hematoma removal, which could have led to massive rebleeding if not treated previously. Neither patient needed a reinsertion of the ventricular drainage or developed chronic hydrocephalus during hospitalization. The hybrid OR enabled the 2 treatment approaches to be performed without the need to transfer the patient, thereby minimizing the transition time between the modalities. Intraoperative cone-beam computed tomography contributed to the evaluation of residual clots. CONCLUSIONS: A hybrid OR may contribute to a combined neuroendoscopic and endovascular treatment for ruptured cerebral aneurysms with severe intraventricular hemorrhage. PMID- 26802872 TI - Letter to the Editor. PMID- 26802871 TI - Balloon-Assisted Fistula Sealing Procedure for Symptomatic Tarlov Cysts. AB - OBJECTIVE: Tarlov cyst is an abnormal expansion of the spinal nerve sleeve, and it communicates with the subarachnoid cavity via a perineural fistula. This study presents our experience of a balloon-assisted fistula sealing procedure in treating Tarlov cyst. METHODS: Twenty-two patients with symptomatic Tarlov cysts were surgically treated. An emulsion balloon was placed into the lumbar subarachnoid cistern through a trocar, so as to temporarily block cerebrospinal fluid flow, then the thecal sac was opened and the inlet of the fistula was sealed by suture of a muscular patch and reinforced by fibrin glue. Finally, the cyst wall was imbricated and the bony cavity was filled with pedicled muscle flaps. RESULTS: Comparing the preoperative and postoperative pain scores according to visual analog scale, 2 patients were slightly improved and 18 patients were substantially improved, including 3 completely pain-free cases. Only 2 patients were unchanged in pain, and both of them had multiple cysts. As a whole, the postoperative pain score was much better than the preoperative score (2.4 vs. 7.5; P < 0.01). Bladder weakness was slightly improved, and bowel dysfunction was almost unchanged after operation. During follow-up, cyst recurrence was found in 1 patient. CONCLUSIONS: The balloon-assisted fistula sealing procedure is safe and effective for Tarlov cyst, especially for the single cyst. It is a good complement to the cyst wall imbricating procedure. PMID- 26802873 TI - Effect of estrogen on morphine- and oxycodone-induced antinociception in a female femur bone cancer pain model. AB - Although estrous cycle has been reported to influence antiociceptive effect of morphine in several pain conditions, its effect on cancer pain is not well established. We investigated the effect of estrogen on morphine antinociception using a bone cancer pain model and compared its potency with that of oxycodone. Female mice were ovariectomized (OVX) for preparation of a femur bone cancer pain (FBC) model. beta-estradiol was subcutaneously (s.c.) administered and antinociceptive effects of opioids was assessed using the von Frey monofilament test. Although morphine (5-20mg/kg, s.c.) did have significant antinociceptive effects in the FBC-OVX group, its effects in the FBC-OVX+beta-estradiol (OVX+E) group was limited. Oxycodone (1-5mg/kg, s.c.) exhibited significant effects in both groups. Expression changes in opioid-related genes (MU-, kappa-, delta opioid receptors, prodynorphin, proenkephalin, proopiomelanocortin) in the spinal and supraspinal sites were examined among the sham-OVX, sham-OVX+E, FBC-OVX, and FBC-OVX+E groups by in situ hybridization. These studies detected a significant increase in prodynorphin in the spinal dorsal horn of the FBC-OVX+E group. Spinal injection of a dynorphin-A antibody to FBC-OVX+E mice restored antinociception of morphine. In conclusion, we detected a differential effect of estrogen on morphine- and oxycodone-induced antinociception in a female FBC model. The effect of morphine was limited with estrogen exposure, which may be due to estrogen- and pain-mediated spinal expression of dynorphin-A. PMID- 26802874 TI - The interaction between reinforcement and inhibitory control in ADHD: A review and research guidelines. AB - The majority of studies which have aimed to identify cognitive and motivational factors at play in ADHD have investigated cognitive-control processes and reinforcement effects in isolation. Notably, in recent years, the interaction between these two processes has been increasingly examined. Here, we aimed to provide a comprehensive and critical review of the behavioral and functional neuroimaging studies that have investigated reinforcement effects on inhibitory control in ADHD. The findings of our meta-analyses show that reinforcement can normalize inhibitory control in children and adolescents with ADHD to the baseline level of controls. Furthermore, the data suggests that inhibitory control may improve to a larger extent in youth with ADHD compared with controls, as a function of reinforcement. Based on (1) this review and meta-analyses, (2) functional neuroimaging studies in healthy populations, and (3) existing ADHD and neurobiological models of dual processes, we propose specific guidelines for future research, which are anticipated to further elucidate processes underlying impulsive behavior associated with ADHD. PMID- 26802875 TI - Clostridium difficile recurrences in Stockholm. AB - Sixty-eight hospital-admitted patients with a first episode of Clostridium difficile infection (CDI) were included and followed up during 1 year. Faeces samples were collected at 1, 2, 6 and 12 months after inclusion and analyzed for the presence of C. difficile toxin B, genes for toxin A, toxin B, binary toxin and TcdC deletion by PCR. All strains were also PCR-ribotyped and the MICs of the isolates were determined against eight antimicrobial agents. In 68 patients initially included, antibiotics, clinical signs and co-morbidities were analyzed and 56 were evaluable for recurrences. The mean number of different antibiotics given during 3 months prior to inclusion was 2.6 (range 0-6). Six patients had not received any antibiotics and three of them had diagnosed inflammatory bowel disease. Thirty-two patients (57%) had either a microbiological or clinical recurrence, 16 of whom had clinical recurrences that were confirmed microbiologically (13, 23%) or unconfirmed by culture (3, 5%). Twenty-nine patients were positive in at least one of the follow-up tests, 16 had the same ribotype in follow-up tests, i.e. relapse, and 13 a different ribotype, i.e., reinfection. Most common ribotypes were 078/126, 020, 023, 026, 014/077, 001 and 005. No strain of ribotype 027 was found. Strains ribotype 078/126 and 023 were positive for binary toxin and were the strains most prone to cause recurrence. All strains were sensitive to vancomycin and metronidazole. Patients with recurrences were significantly older (p = 0.02) and all patients had a high burden of comorbidities, which could explain the high fatality rate, 26 (38%) patients died during the 1-year follow-up. PMID- 26802876 TI - The nature of non-appendicular anterior paired projections in Palaeozoic total group Euarthropoda. AB - Recent studies have clarified the segmental organization of appendicular and exoskeletal structures in the anterior region of Cambrian stem-group Euarthropoda, and thus led to better understanding of the deep evolutionary origins of the head region in this successful animal group. However, there are aspects of the anterior organization of Palaeozoic euarthropods that remain problematic, such as the morphological identity and significance of minute limb like projections on the anterior region in stem and crown-group representatives. Here, we draw attention to topological and morphological similarities between the frontal filaments of extant Crustacea and the embryonic frontal processes of Onychophora, and distinctive anterior paired projections observed in several extinct total-group Euarthropoda. Anterior paired projections are redescribed in temporally and phylogenetically distant fossil taxa, including the gilled lobopodians Kerygmachela kierkegaardi and Pambdelurion whittingtoni, the bivalved stem-euarthropod Canadaspis perfecta, the larval pycnogonid Cambropycnogon klausmuelleri, and the mandibulate Tanazios dokeron. Developmental data supporting the homology of the 'primary antennae' of Onychophora, the 'frontal appendages' of lower-stem Euarthropoda, and the hypostome/labrum complex of Deuteropoda, argue against the morphological identity of the anterior paired projections of extant and extinct panarthropods as a pair of pre-ocular appendages. Instead, we regard the paired projections of fossil total-group euarthropods as non-appendicular evaginations with a likely protocerebral segmental association, and a possible sensorial function. The widespread occurrence of pre-ocular paired projections among extant and extinct taxa suggests their potential homology as fundamentally ancestral features of the anterior body organization in Panarthropoda. Non-appendicular paired projections with a sensorial function may reflect a critical--yet previously overlooked- component of the panarthropod ground pattern. PMID- 26802877 TI - Deiodinase knockdown affects zebrafish eye development at the level of gene expression, morphology and function. AB - Retinal development in vertebrates relies extensively on thyroid hormones. Their local availability is tightly controlled by several regulators, including deiodinases (Ds). Here we used morpholino technology to explore the roles of Ds during eye development in zebrafish. Transcriptome analysis at 3 days post fertilization (dpf) revealed a pronounced effect of knockdown of both T4 activating Ds (D1D2MO) or knockdown of T3-inactivating D3 (D3bMO) on phototransduction and retinoid recycling. This was accompanied by morphological defects (studied from 1 to 7 dpf) including reduced eye size, disturbed retinal lamination and strong reduction in rods and all four cone types. Defects were more prominent and persistent in D3-deficient fish. Finally, D3-deficient zebrafish larvae had disrupted visual function at 4 dpf and were less sensitive to a light stimulus at 5 dpf. These data demonstrate the importance of TH activating and -inactivating Ds for correct zebrafish eye development, and point to D3b as a central player. PMID- 26802878 TI - Endoglin (CD105) coordinates the process of endometrial receptivity for embryo implantation. AB - Endoglin is a TGF-beta receptor that is expressed in uterine endothelial and stromal cells in addition to trophoblast expression. However, the functional importance of endoglin in the embryo implantation process is not clear. We observed endoglin expression in the endometrium throughout the stages of its receptivity; however, its expression was enhanced during the receptive stage. Endoglin expression was predominant in epithelial cells of the lumen and glands, but showed a milder expression in stromal cells. Endoglin expression was initially observed in the primary decidual zone and later extended to the secondary decidua zone. Knockdown of endoglin via siRNA reduced the implantation sites along with the blastocyst numbers. Mouse blastocyst with endoglin-silenced endometrial epithelial cells (human and mouse origin) showed poor trophoblast outgrowth, which suggests an essential role for endoglin during endometrial receptivity. In conclusion, our findings reveal the association of endoglin with endometrial receptivity, which is important for embryo attachment. PMID- 26802879 TI - Up-regulation of genes involved in the insulin signalling pathway (IGF1, PTEN and IGFBP1) in the endometrium may link polycystic ovarian syndrome and endometrial cancer. AB - BACKGROUND: Endometrial cancer (EC) is the most common gynaecological cancer amongst women in the UK. Although previous studies have found that women with polycystic ovary syndrome (PCOS) have at least a three-fold increase in endometrial cancer (EC) risk compared to women without PCOS, the precise molecular mechanisms which link between PCOS and EC remain unclear. It has been suggested that insulin resistance may contribute to the increased risk of EC in PCOS. The specific expression of genes related to the insulin-signalling pathway including the IGF system in the endometrium of women with PCOS has however never been measured and compared to that in women with EC without PCOS and control women without EC or PCOS. . OBJECTIVES: To test the hypothesis that insulin signalling plays a key role in the development of EC in women with PCOS by measuring and comparing the expression of three key genes involved in the insulin signalling pathway (IGF1, PTEN and IGFBP1) in endometrial tissue obtained from three groups of women; PCOS without EC, women with EC without PCOS and non-PCOS women without EC (controls). We also aimed to determine the correlation between the gene expressions to various clinical variables among participants. METHODS: This was a cross-sectional study of 102 women in 3 groups (PCOS, EC and controls) at a University teaching hospital in the United Kingdom. Clinical assessment (blood pressure, body mass index (BMI) and waist-hip-circumference ratio), venepuntures (fasting blood sugar, insulin, lipid profile, hormones) and endometrial tissue biopsies were taken in all participants. Endometrial tissue RNA extraction was performed before real time polymerase-chain-reaction for the genes of interest (IGF1, IGFBP1 and PTEN) was carried out. To compare the baseline characteristics of the study population, One-Way-ANOVA test or the Independent t-test was used. For variables that were not normally distributed, the Spearman correlation test was used to calculate the r value. A "p" value of <0.05 was considered statistically significant. RESULTS: IGF1, IGFBP1 and PTEN gene expression were significantly up-regulated in the endometrium of PCOS and EC women compared to controls. However there was no significant difference in the expression of these genes in PCOS compared to EC endometrium. The BMI of women with PCOS and controls, were not significantly different (29.28 (+/- 2.91) vs 28.58 (+/- 2.62) kg/m(2)) respectively, women with EC however had a higher mean BMI (32.22 (+/- 5.70) kg/m(2)). PCOS women were younger (31.8 (+/- 5.97) years) than women with EC (63.44 (+/- 10.07) years) and controls (43.68 (+/- 13.12) years). The changes in gene expression were independent of BMI, waist hip ratio, estradiol and androgen levels. Protein validation test in the serum samples in the three groups were consistent with the gene findings. CONCLUSION: Women with PCOS and EC have an increased endometrial expression of genes (IGF1, IGFBP1 and PTEN) involved in the insulin signalling pathway compared with control women. This may explain the increased risk of EC in PCOS women. This study provides a strong basis for clinical trials aiming to prevent EC in women with PCOS by investigating drugs targeting the insulin signalling pathway. This panel of genes may also serve as clinically useful early biomarkers which predict which women with PCOS will go on to develop EC. PMID- 26802880 TI - Patterns of thyroid hormone receptor expression in zebrafish and generation of a novel model of resistance to thyroid hormone action. AB - Resistance to thyroid hormone can be due to heterozygous, dominant negative (DN) THRA (RTHalpha) or THRB (RTHbeta) mutations, but the underlying mechanisms are incompletely understood. Here, we delineate the spatiotemporal expression of TH receptors (TRs) in zebrafish and generated morphants expressing equivalent amounts of wild-type and DN TRalphas (thraa_MOs) and TRbetas (thrb_MOs) in vivo. Both morphants show severe developmental abnormalities. The phenotype of thraa_MOs includes brain and cardiac defects, but normal thyroid volume and tshba expression. A combined modification of dio2 and dio3 expression can explain the high T3/T4 ratio seen in thraa_MOs, as in RTHalpha. Thrb_MOs show abnormal eyes and otoliths, with a typical RTHbeta pattern of thyroid axis. The coexpression of wild-type, but not mutant, human TRs can rescue the phenotype in both morphants. High T3 doses can partially revert the dominant negative action of mutant TRs in morphant fish. Therefore, our morphants recapitulate the RTHalpha and RTHbeta key manifestations representing new models in which the functional consequences of human TR mutations can be rapidly and faithfully evaluated. PMID- 26802881 TI - [The Scientific Societies and their social responsability in health]. PMID- 26802882 TI - [How do gastroenterologists in Peru deal with Helicobacter pylori infection? Study based on a survey conducted in 2014]. AB - OBJECTIVE: This study seeks to identify, through a survey, how Peruvian gastroenterologists deal with Helicobacter pylori infection. MATERIAL AND METHODS: Gastroenterologists answered a survey concerning diagnosis and treatment of Helicobacter pylori infection. RESULTS: 177 valid answers were obtained (29.6% of the population). Within the main results, 77.4% use endoscopy + biopsy (histology) for diagnosis, 95.5% choose proton pump inhibitor + clarithromycin + amoxicillin as first line treatment and 50.0% check for eradication 4-6 weeks after treatment. CONCLUSIONS: Most gastroenterologists in Peru deal adequately with Helicobacter pylori infection, although follow-up aspects could be improved. PMID- 26802883 TI - [Comparison of the prognostic value of mortality Child Pugh Score and forecasting models of chronic liver disease in patients with decompensated cirrhosis of the Hospital Nacional Cayetano Heredia, Lima-Peru]. AB - INTRODUCTION: The assessment of prognosis is an essential part of the evaluation of all patients with liver cirrhosis. Currently continues to develop new models to optimize forecast accuracy mortality score is calculated by the Child-Turcotte Pugh (CTP) and the model for end-stage liver disease (MELD). OBJECTIVE: Compare the prognostic accuracy of hospital mortality and short-term mortality CTP, MELD and other models in patients with decompensated liver cirrhosis. MATERIAL AND METHODS: Prospective descriptive study, comparison type of diagnostic test that included 84 patients. The score CTP, MELD and other models were calculated on the first day of hospitalization. The prognostic accuracy of mortality was assessed by the area under the ROC curve (AUROCs) of score CTP, MELD and other models. RESULTS: Hospital mortality and mortality in the short-term monitoring was 20 (23.8%) and 44 (52.4%), respectively. The AUROCs CTP, MELD, MELD Na, MESO, iMELD, RefitMELD and RefitMELD Na to predict hospital mortality was 0.4488, 0.5645, 0.5426, 0.5578, 0.5719, 0.5598 and 0.5754; and to predict short-term mortality was 0.5386, 0.5747, 0.5770, 0.5781, 0.5631, 0.5881 and 0.5693, respectively. By comparing each AUROCs of the CTP score, MELD and other models proved to be no better than the other (p>0.05). CONCLUSION: This study has not shown the predictive utility of the CTP score, MELD and other models (MELD Na, MESO, iMELD, Refit Refit MELD and MELD Na) to evaluate hospital mortality or short-term mortality in a sample of patients with decompensated cirrhosis of the Hospital Cayetano Heredia. PMID- 26802884 TI - Surgical or endoscopic management for post-ERCP large transmural duodenal perforations: a randomized prospective trial. AB - INTRODUCTION: Duodenal perforations are an uncommon adverse event during ERCP. Patients can develop significant morbidity and mortality. Even though surgery has been used to manage duodenal complications, therapeutic endoscopy has seen significant advances. OBJECTIVE: To compare endoscopic approach with surgical intervention in patients with duodenal perforations post-ERCP. MATERIAL AND METHODS: prospective randomized study in a tertiary center with 23 patients divided in 2 groups. Within 12 hours after the event, the patients underwent endoscopic or surgical approach. Endoscopic approach included closure of the perforation with endoclips and SEMS. Surgical repair included hepaticojejunostomy, suture of the perforation or duodenal suture. The success was defined as closure of the defect. Secondary outcomes included mortality, adverse events, days of hospitalization and costs. RESULTS: The success was 100% in both groups. There was one death in the endoscopic group secondary to sepsis. There was no statistical difference in mortality or adverse events. We noticed statistical difference in favor of the endoscopic group considering shorter hospitalization (4.1 days versus 15.2 days, with p=0.0123) and lower cost per patient (U$14,700 versus U$19,872, with p=0.0103). CONCLUSIONS: Endoscopic approach with SEMS and endoclips is an alternative to surgery in large transmural duodenal perforations post-ERCP. PMID- 26802885 TI - [Abdominal Tuberculosis in children and adolescents. A diagnostic challenge]. AB - OBJECTIVE: To present our experience with abdominal tuberculosis in children and adolescents treated in our hospital from 2003 - 2014. MATERIAL AND METHODS: It is a retrospective study. We have collected clinical records of inpatients <20 years old who were admitted at Hipolito Unanue Hospital from January 2003 to July 2014, with diagnosis of abdominal tuberculosis. RESULTS: Among the overall 30 patients, 16 (53.33%) were female and 14 (46.67%) were male. The mean age of all patients was 16.5 years. The most common clinical features were abdominal pain in 29 (96.67%), fever in 26 (86.67%), ascites in 23 (76.67%) and loss of weight in 21 (70%). 63.33% of the patients were eutrophics, 13.34% were overweight or obese and only 23.33% suffered of malnutrition. TB contact was present in 10 (33.33%). Positive tuberculin skin tests were seen in 10%. Extra-abdominal tuberculosis was found in 22 patients (63.32%). 12 cases had coexisting pulmonary tuberculosis and 4 cases had pleural effusion. 12 patients (40%) had tuberculous peritonitis; 12 patients (40%) had intestinal tuberculosis and peritoneal tuberculosis and 4 patients (13.33%) had intestinal tuberculosis. Bacteriological confirmation of tuberculosis was achieved in 10 cases (33.33%). Antituberculous therapy for 6 months was effective in 29 cases. One patient died who multifocal tuberculosis with HIV had associated. CONCLUSIONS: Abdominal tuberculosis is seen in 4.37% of children affected with tuberculosis, of which over 63% will have extra abdominal manifestations. Abdominal tuberculosis should be considered in patients with abdominal pain, fever, weight loss and abnormal chest radiography. Imaging can be useful for early diagnosis of abdominal tuberculosis. PMID- 26802886 TI - [AIMS65 score validation for upper gastrointestinal bleeding in the National Hospital Cayetano Heredia]. AB - OBJECTIVE: To validate the score AIMS65 in patients with upper gastrointestinal bleeding, in terms of mortality and rebleeding a 30-day event. MATERIAL AND METHODS: Patients included were those with higher age to 18 years attending the Hospital Nacional Cayetano Heredia during the period May 2013 to December 2014, by upper gastrointestinal bleeding. Data were analyzed using ROC curve (Receiver Operating Characteristic) and the area was obtained under the curve (AUC) to properly qualify the score AIMS65. RESULTS: 209 patients were included, 66.03% were male, with an average age of 58.02 years. The mortality rate was 7.65%, the multiorgan failure the most common cause of death. Plus 3.82% of the patients had recurrent bleeding and 11% required a transfusion of more than 2 units of blood. When analyzing the ROC curve with AIMS65 and mortality score a value of 0.9122 is reported; identifying it as cutoff greater than or equal to 3 value in the score AIMS65 to discriminate patients at high risk of death, likewise the ROC curve was analyzed for recurrence of bleeding with a value of 0.6266 and the need to Transfusion of packed red blood cells over two a value of 0.7421. And it was determined the average hospital stay with a value of 4.8 days, however, no correlation was found with the score AIMS65. CONCLUSIONS: AIMS65 score is a good predictor of mortality, and is useful for predicting the need for transfusion of more than 2 globular packages. However it is not a good predictor for recurrence of bleeding, or hospital stay. PMID- 26802887 TI - Endoscopic-ultrasound versus percutaneous-guided celiac plexus block for chronic pancreatitis pain. A systematic review and meta-analysis. AB - BACKGROUND: Abdominal pain is present in the vast majority of patients with chronic pancreatitis, being frequently debilitating. Celiac plexus block (CPB) is an interventional technique that can be considered to provide a temporary pain relief. OBJECTIVE: To estimate the effectiveness and safeness of endoscopic ultrasound (EUS) comparing with percutaneous-guided CBP in patients with pancreatic pain. METHODS: A systematic review of English and non-English articles using MEDLINE, EMBASE, LILACS and COCHRANE (via BVS). STUDY SELECTION AND DATA EXTRACTION: Only randomized control trials (RCT) comparing the beneficial and harmful effects of EUS and percutaneous-guided celiac plexus block for managing pancreatic pain were included. Data was extracted and analyzed on variables including pain relief and related procedure complications. RESULTS: Two RCT met the inclusion criteria. Both studies assessed the primary outcome (reduction on pain score) and evaluated adverse effects. The drugs injected were the same; nevertheless percutaneous technique was guided by fluoroscopy in one study and by computer tomography (CT) in other. The results showed that the EUS-CPB group was more effective to reduce pain score after 4 weeks after the procedure, with risk of bias to do this affirmation. No statistical difference in pain relief at 1, 8 and 12 weeks and in complications rates. CONCLUSIONS: Based on this systematic review and meta-analysis, no statistically significant difference was noted in pain relief and complications for EUS and percutaneous - CPB. PMID- 26802888 TI - [Cholangiocarcinoma in the middle third of the bile duct treated with radical surgery in Guillermo Almenara Hospital, Lima, Peru]. AB - We report the case of a patient who had the initial diagnosis of tumor in the bile duct in the middle third. Patient presented with lost weight of 10 kilograms in two months and moderate epigastric pain, no jaundice. The patient underwent radical surgery of the bile duct with multiple freeze biopsy surgical margins, intraoperative choledochoscopy, intraoperative cholangiography and reconstruction bilioenteric anastomosis Y Roux transmesocolic, he had a great recovery and early discharge. The pathological results showed moderately differentiated tubular adenocarcinoma on the basis of an adenoma. Negatives retroperitoneal, retropancreatic, pericholedochal, lesser curvature and negative hepatic artery nodes, and extension of surgical margins free of neoplasia proximal and distal edges. R0 surgery. pT1N0Mx. Stage 1. After the optimal surgical outcomes, is managed by liver and biliary tract surgery service and medical oncology service for regular monitoring and controls. We present here the sequence of events and a review of the literature. PMID- 26802889 TI - [Acute necrotizing esophagitis (black esophagus) with secondary severe stenosis]. AB - We report the case of a 67 years old patient with a history of diabetes mellitus, atrial fibrillation and chronic renal failure, who developed diabetic ketoacidosis and severe sepsis, later presenting an acute necrotizing esophagitis, and then a esophageal stenosis requiring treatment with self expanding esophageal prosthesis with good clinical results. PMID- 26802890 TI - [VIPoma in retroperitoneum of elderly, cause of chronic diarrhea in uncommon location]. AB - Chronic secretory diarrhea is a frequent entity. Causes are multiple, that is why reaching final diagnosis can result in delay with complications that this causes in the general condition of the patient. We present the case of one older adult with chronic diarrhea, mild hypokalemia and metabolic hyperchloremic acidosis secondary to a VIPoma in retroperitoneum which is an unusual location of this type of tumor that was diagnosed by biopsy guided by tomography. PMID- 26802891 TI - [The gastric volvulus as a cause of dyspnea. A case report]. AB - The gastric volvulus is a not very frequent entity that can show up in acute form or chronic. The acute volvulus can show up with the triad of Borchardt, the chronic one can be asymptomatic and its diagnosis is usually incidental. We present shows a case of an airplane pilot that presents dyspnea to the medium efforts with cough related with episodes of gastric acidity mainly after profuse foods. The diagnostic confirmation was carried out by means of radiological simple and contrasted studies. A surgical intervention was performed and the symptoms disappeared without other alterations in a period of pursuit of one year. PMID- 26802892 TI - [Wilson disease: liver form]. AB - Wilson disease (WD) is a disorder of copper metabolism that is inherited as an autosomal recessive, which produces toxic copper accumulation mainly in the liver and brain, in general has two ways presentation, liver at early ages and neurological in later ages. We present the case of a female patient of 21 years diagnosed of WD in liver cirrhosis that started with an edematous ascites without any neurological symptoms despite the age. Their laboratory studies showed decrease in serum ceruloplasmin and high cupruria within 24 hours of the disease , characteristic data of WD. Although WD is not a common disease should be suspected in all chronic liver disease of unknown etiology with negative viral markers and autoimmunity with or without neurological manifestations as soon as posible and starting treatment with copper chelating mainly leads to a substantial improvement the prognosis of these patients. PMID- 26802893 TI - [Colorectal Cancer in Latin America: a disease we need to remember]. PMID- 26802894 TI - Regulation of dietary glutamine on the growth, intestinal function, immunity and antioxidant capacity of sea cucumber Apostichopus japonicus (Selenka). AB - The present study examined the effects of dietary glutamine (Gln) on the growth, intestinal function, immunity and antioxidant capacity of sea cucumber Apostichopus japonicus (Selenka). The specific growth rate, intestinal morphology, activity of digestive enzymes, activity and gene expression of lysozyme and antioxidative enzymes of the sea cucumbers were determined after feeding 5 experimental diets with additions of increasing levels of Gln (at 0%, 0.4%, 0.8%,1.2% and 1.6%, respectively) for 60 days. We discovered that the specific growth rate of the sea cucumbers in 0.4%, 0.8% and 1.2% groups increased 35.3%, 27.3% and 24.1%, respectively, compared to the control (0%) group with significant differences. Dietary Gln can improve the intestinal function of the sea cucumbers by increasing the activities of trypsin and lipase in the intestine and the villus height and villus density of the intestine, eventhough significant differences were not observed in some groups. 0.4%-0.8% of dietary Gln can significantly increase the activity of lysozyme (LSZ) in the coelomic fluid of the sea cucumbers. Significant improvements were observed on the SOD activity in coelomic fluid of the sea cucumbers fed diets supplemented with 0.4%-1.6% of Gln compared to the control group. Similarly, the CAT activity in coelomic fluid of the sea cucumbers significantly increased in 0.8%, 1.2% and 1.6% groups compared to the control and 0.4% groups. Change pattern of the activity of CAT was consistent with the change pattern of the expression of CAT gene, indicating the dietary Gln can up-regulate the expression of CAT gene and consequently promote the secretion of CAT. However, the down-regulation of the expression of SOD gene by dietary Gln were observed in almost all of the treatment groups, which is in contrast with the change pattern of the activity of SOD, indicating the negative feedback regulation of the secretion of SOD on the expression of SOD gene. In summary, the suitable supplementation levels of Gln in diets of sea cucumber A. japonicus are 0.4%-0.8%, based on the effectiveness of dietary Gln on the growth, intestinal function, immunity and antioxidant capacity of the sea cucumbers. PMID- 26802895 TI - A new Gal/GalNAc-specific lectin from the mussel Mytilus trossulus: Structure, tissue specificity, antimicrobial and antifungal activity. AB - In the present study, a new Gal/GalNAc specific lectin from the mussel Mytilus trossulus (designated as MTL) was identified, and its expression levels, both in tissues and toward pathogen stimulation, were then characterized. The MTL primary structure was determined via cDNA sequencing. Deduced sequence of 150 amino acid residues showed 89% similarity to lectins from the mussels Crenomytilus grayanus and Mytilus galloprovincialis that were the first members of a new family of zoolectins. The results indicated that the MTL might be involved in immune response toward pathogen infection, and it might perform different recognition specificity toward bacteria or fungi. PMID- 26802897 TI - Research progress on the reproductive and non-reproductive endocrine tumors by estrogen-related receptors. AB - Oncologists have traditionally considered that tumorigenesis are closely related to classical nuclear estrogen receptors (ERs), such as estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta), through the ligands binding and target gene transcription induction. Estrogen-related receptors (ERRs) have similar structures with ERs, which are also gradually thought to be relevant to reproductive endocrine tumor diseases, even non-reproductive endocrine tumors. In this review, different subtypes of ERRs and their structures firstly will be introduced, then the expression patterns in gynecological oncology (i.e., breast cancer, endometrial cancer, and ovarian cancer), male genitourinary system malignancy especially prostatic cancer along with other non-reproductive endocrine tumors (i.e., lung cancer, colorectal cancer, and liver cancer) will be described, and simultaneously the role of tumorigenesis related to ERRs will be discussed. Therefore, the review is benefit to explore the way of tumor prevention and treatment. PMID- 26802896 TI - Prebiotics effect on immune and hepatic oxidative status and gut morphology of white sea bream (Diplodus sargus). AB - The aim of this study was to evaluate the effects of short-chain fructooligosaccharides (scFOS), xylooligosaccharides (XOS) and galactooligosaccharides (GOS) on immune and hepatic oxidative status, and gut morphology of white sea bream juveniles. Four diets were formulated: a control diet with fish meal (FM) and plant feedstuffs (PF) (30FM:70PF) and three test diets similar to the control but supplemented with 1% of scFOS, XOS or GOS. Dietary prebiotic incorporation did not affect total blood cell counts, hematocrit, hemoglobin, red blood indices or differential white blood cell counts. Fish fed GOS had lower ACH50 and nitric oxide than fish fed control diet. XOS enhanced immune status through the increase in alternative complement pathway (ACH50), lysozyme and total immunoglobulin. The higher activity of glucose 6 phosphate dehydrogenase in fish fed FOS compared to the other dietary groups was the only related antioxidant enzyme affected by prebiotics in the liver. GOS ameliorated the precocious adverse effects of PF based diet on gut histomorphology, as denoted by the lower incidence of histological alterations in fish fed GOS for 15 days. In conclusion, XOS and GOS at 1% might have potential to be used as prebiotics in white sea bream juveniles. PMID- 26802898 TI - TCTP regulates spindle microtubule dynamics by stabilizing polar microtubules during mouse oocyte meiosis. AB - Dynamic changes in spindle structure and function are essential for maintaining genomic integrity during the cell cycle. Spindle dynamics are highly dependent on several microtubule-associated proteins that coordinate the dynamic behavior of microtubules, including microtubule assembly, stability and organization. Here, we show that translationally controlled tumor protein (TCTP) is a novel microtubule-associated protein that regulates spindle dynamics during meiotic maturation. TCTP was expressed and widely distributed in the cytoplasm with strong enrichment at the spindle microtubules during meiosis. TCTP was found to be phosphorylated during meiotic maturation, and was exclusively localized to the spindle poles. Knockdown of TCTP impaired spindle organization without affecting chromosome alignment. These spindle defects were mostly due to the destabilization of the polar microtubules. However, the stability of kinetochore microtubules attached to chromosomes was not affected by TCTP knockdown. Overexpression of a nonphosphorylable mutant of TCTP disturbed meiotic maturation, stabilizing the spindle microtubules. In addition, Plk1 was decreased by TCTP knockdown. Taken together, our results demonstrate that TCTP is a microtubule-associating protein required to regulate spindle microtubule dynamics during meiotic maturation in mouse oocytes. PMID- 26802899 TI - How does alpha-actinin-3 deficiency alter muscle function? Mechanistic insights into ACTN3, the 'gene for speed'. AB - An estimated 1.5 billion people worldwide are deficient in the skeletal muscle protein alpha-actinin-3 due to homozygosity for the common ACTN3 R577X polymorphism. alpha-Actinin-3 deficiency influences muscle performance in elite athletes and the general population. The sarcomeric alpha-actinins were originally characterised as scaffold proteins at the muscle Z-line. Through studying the Actn3 knockout mouse and alpha-actinin-3 deficient humans, significant progress has been made in understanding how ACTN3 genotype alters muscle function, leading to an appreciation of the diverse roles that alpha actinins play in muscle. The alpha-actinins interact with a number of partner proteins, which broadly fall into three biological pathways-structural, metabolic and signalling. Differences in functioning of these pathways have been identified in alpha-actinin-3 deficient muscle that together contributes to altered muscle performance in mice and humans. Here we discuss new insights that have been made in understanding the molecular mechanisms that underlie the consequences of alpha actinin-3 deficiency. PMID- 26802900 TI - Current status of data on cangrelor. AB - P2Y12 receptor inhibition in addition to aspirin is the cornerstone of treatment in patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI). Despite advances in contemporary antithrombotic therapy, periprocedural thrombotic complications such as myocardial infarction and stent thrombosis remain a major concern in patients treated with PCI. Current practice guidelines recommend treatment with a P2Y12 receptor inhibitor as early as possible in patients with ACS. Existing oral P2Y12 receptors inhibitors (clopidogrel, prasugrel, or ticagrelor) have several limitations such as delayed onset and offset of action, interindividual variation, and only oral availability. Cangrelor, an intravenous, fast-onset, direct-acting P2Y12 receptor inhibitor offers potent platelet inhibition that is rapidly reversible. In large randomized trials, cangrelor has shown substantial reduction in ischemic events with no increase in severe bleeding compared with clopidogrel among patients undergoing PCI. Cangrelor is approved as an adjunct to PCI to reduce the risk of periprocedural MI, repeat coronary revascularization, and stent thrombosis in patients who have not been pretreated with a P2Y12 receptor inhibitor and are not receiving a glycoprotein IIb/IIIa inhibitor. This review aims at providing a comprehensive analysis of the current evidence pertaining to the role of cangrelor in contemporary practice. PMID- 26802901 TI - Paraptosis in the anti-cancer arsenal of natural products. AB - Given the problems with malignant cancer cells showing innate and acquired resistance to apoptosis, we need alternative means to induce cell death in cancer. Paraptosis is a type of programmed cell death that is characterized by dilation of the endoplasmic reticulum (ER) and/or mitochondria. Although relatively little is known regarding the molecular basis of paraptosis, the underlying mechanism clearly differs from that of apoptosis. Recent studies have shown that various natural products, including curcumin, celastrol, 15d-PGJ2, ophiobolin A, and paclitaxel, demonstrate anti-cancer effects by inducing the paraptosis-associated cell death, which was commonly characterized by vacuolation derived from the ER. Perturbation of cellular proteostasis due to proteasomal inhibition and disruption of sulfhydryl homeostasis, generation of reactive oxygen species, and/or imbalanced homeostasis of ions (e.g., Ca(2+) and K(+)) appear to contribute to the accumulation of misfolded protein and proteotoxicity in this process. Given the pathophysiological importance of paraptosis and the debate regarding the importance of apoptosis in solid tumor, we need to collect the available knowledge regarding paraptosis and suggest future directions in the field. Here, we review the morphological and biochemical features of paraptosis, the natural products that induce paraptosis-associated cell death, their proposed mechanisms, and the significance of paraptosis as a potential anti-cancer strategy. Such work and future clarifications should enable the development of new strategies for preventing cancer and/or combating malignant cancer. PMID- 26802902 TI - Probing the role of lambda6 immunoglobulin light chain dimerization in amyloid formation. AB - Light chain amyloidosis (AL) is a lethal disease associated with the deposition of misfolded immunoglobulin light chains (LC) as amyloid fibrils in the extracellular space of vital organs. The exact mechanisms of LC self-assembly and the molecular basis leading to cellular and organ failure still remain poorly understood. In this study, we investigated the relationship between the quaternary structure, the stability and the amyloidogenecity of LC variable domain (VL) from the lambda6 germline. We observed that the amyloidogenic lambda6 Wil and its non-amyloidogenic counterpart Jto dimerize in a concentration dependent manner and that the dimer affinity is considerably decreased in the presence of a high ionic strength. Our results showed that the dimeric state delays the structural conversion associated with amyloid formation and that the monomer is critical to initiate amyloidogenesis. Thermal and chemical unfolding studies revealed that the dimeric state of VL lambda6 has an equivalent stability to the monomer. This indicates that the protective effect of dimerization is not related to thermodynamic stability but, most likely, resides in specific structural features. The toxicity of monomeric Jto and Wil as well as fibrillar aggregates was evaluated on cardiomyoblasts and ThT-negative proteospecies reduced cellular viability when employed at high concentration. This study provides novel insights into the complex process of LC amyloidogenesis and suggests that dimer stabilization constitutes a promising strategy to prevent self-assembly and amyloid deposition. PMID- 26802903 TI - 2-Methoxy-6-acetyl-7-methyljuglone (MAM), a natural naphthoquinone, induces NO dependent apoptosis and necroptosis by H2O2-dependent JNK activation in cancer cells. AB - Redox signaling plays a fundamental role in maintaining cell physiological activities. A deregulation of this balance through oxidative stress or nitrosative stress has been implicated in cancer. Here, we reported that 2 methoxy-6-acetyl-7-methyl juglone (MAM), a natural naphthoquinone isolated from Polygonum cuspidatum Sieb. et Zucc, caused hydrogen peroxide (H2O2) dependent activation of JNK and induced the expression of inducible nitric oxide synthase (iNOS), thereby leading to nitric oxide (NO) generation in multiple cancer cells. Nitrosative stress induced necroptosis in A549 lung cancer cells, but resulted in caspase-dependent intrinsic apoptosis in B16-F10 melanoma and MCF7 breast cancer cells. In addition, a decrease in GSH/GSSG levels accompanied with increased ROS production was observed. Reversal of ROS generation and cell death in GSH pretreated cells indicated the involvement of GSH depletion in MAM mediated cytotoxicity. In summary, a natural product MAM induced NO-dependent multiple forms of cell death in cancer cells mediated by H2O2-dependent JNK activation in cancer cells. GSH depletion might play an initial role in MAM-induced cytotoxicity. PMID- 26802904 TI - Commentary on "Bach1 differentially regulates distinct Nrf2-dependent genes in human venous and coronary artery endothelial cells adapted to physiological oxygen levels" by Chapple et al. PMID- 26802905 TI - High risk of adrenal toxicity of N1-desoxy quinoxaline 1,4-dioxide derivatives and the protection of oligomeric proanthocyanidins (OPC) in the inhibition of the expression of aldosterone synthetase in H295R cells. AB - Quinoxaline 1,4-dioxide derivatives (QdNOs) with a wide range of biological activities are used in animal husbandry worldwide. It was found that QdNOs significantly inhibited the gene expression of CYP11B1 and CYP11B2, the key aldosterone synthases, and thus reduced aldosterone levels. However, whether the metabolites of QdNOs have potential adrenal toxicity and the role of oxidative stress in the adrenal toxicity of QdNOs remains unclear. The relatively new QdNOs, cyadox (CYA), mequindox (MEQ), quinocetone (QCT) and their metabolites, were selected for elucidation of their toxic mechanisms in H295R cells. Interestingly, the results showed that the main toxic metabolites of QCT, MEQ, and CYA were their N1-desoxy metabolites, which were more harmful than other metabolites and evoked dose and time-dependent cell damage on adrenal cells and inhibited aldosterone production. Gene and protein expression of CYP11B1 and CYP11B2 and mRNA expression of transcription factors, such as NURR1, NGFIB, CREB, SF-1, and ATF-1, were down regulated by N1-desoxy QdNOs. The natural inhibitors of oxidant stress, oligomeric proanthocyanidins (OPC), could upregulate the expression of diverse transcription factors, including CYP11B1 and CYP11B2, and elevated aldosterone levels to reduce adrenal toxicity. This study demonstrated for the first time that N1-desoxy QdNOs have the potential to be the major toxic metabolites in adrenal toxicity, which may shed new light on the adrenal toxicity of these fascinating compounds and help to provide a basic foundation for the formulation of safety controls for animal products and the design of new QdNOs with less harmful effects. PMID- 26802906 TI - Extraperitoneal Robotic-Assisted Para-Aortic Lymphadenectomy in Gynecologic Cancer Staging: Current Evidence. AB - We reviewed the current evidence on the safety, effectiveness, and applicability of extraperitoneal robotic-assisted para-aortic lymphadenectomy (ExtRA-PAL) as the staging procedure of gynecologic malignancies. PubMed (MEDLINE), Scopus, Web of Science databases, and ClinicalTrials.gov were searched for original studies reporting outcomes of ExtRA-PAL. Quality of the included studies and their level of recommendation were assessed using the Grading of Recommendations, Assessment, Development, and Evaluation and the American College of Obstetricians and Gynecologists guidelines, respectively. Overall, 62 studies were identified; after a process of evidence acquisition 5 original investigations were available for this review that included 98 patients undergoing ExtRA-PAL. The main surgical indication was staging for cervical cancer (n = 71, 72%). The mean (SD) number of para-aortic node yielded was 15.4 (+/-4.7) nodes. Blood transfusion and intraoperative complication rates were 2% and 6%, respectively. ExtRA-PAL was completed in 88 patients (90%). Six (6%) and 4 (4%) patients had conversion to other minimally invasive procedures and open surgery, respectively. Success rate was 99% among patients undergoing ExtRA-PAL without concomitant procedures. Overall, mean (SD) length of hospital stay was 2.8 (+/-0.5) days. Twenty-four patients (24%) developed postoperative events. According to the Clavien-Dindo grading system, grades IIIa and IIIb morbidity rates were 12% and 2%, respectively. No grades IV and V morbidity occurred. ExtRA-PAL is associated with a high success rate and a relative low morbidity rate. However, because of the limited data on this issue, further studies are warranted to assess the long-term effectiveness of this procedure. PMID- 26802907 TI - Intravenous Leiomyomatosis in the Parametrium. AB - Laparoscopic imaging of intravenous leiomyomatosis is rare. We report a 35-year old woman with uterine leiomyomatosis, laparoscopic hysterectomy exposed parametrial vessels with whitish plugs extending intravascularly toward the pelvic sidewall. Complete surgical resection and long-term follow-up are important. PMID- 26802908 TI - Safety of Manual Morcellation After Vaginal or Laparoscopic-assisted Vaginal Hysterectomy. AB - STUDY OBJECTIVE: To determine the safety of manual vaginal morcellation by evaluating the rates of incidental uterine malignancy and manual vaginal morcellation after vaginal or laparoscopic-assisted vaginal hysterectomy. DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: University of Texas Southwestern Medical Center, Dallas, TX. PATIENTS: Women (n = 1,629) undergoing vaginal or laparoscopic-assisted vaginal hysterectomy. INTERVENTIONS: Vaginal hysterectomy (n = 1,091) or laparoscopic-assisted vaginal hysterectomy (n = 538) with and without scalpel morcellation. MEASUREMENTS AND MAIN RESULTS: The number of uterine malignancies, rate of vaginal morcellation, surgical indications, pathology diagnoses, and uterine weights were evaluated. Chi-square analysis was used to compare categoric data, and analysis of variance was used to compare uterine weights. There were no cases of leiomyosarcomas. There were 2 other sarcomas, 4 smooth muscle tumors of uncertain malignant potential, and 8 endometrial adenocarcinomas. The vaginal morcellation rate was 19.4%, but no malignancy was morcellated. Myomas were more common preoperatively and histologically in morcellated specimens. Mean (+/- standard deviation) uterine weights for morcellated versus nonmorcellated laparoscopic-assisted vaginal hysterectomy specimens were 285.5 +/- 159.3 versus 140.1 +/- 83.6 g (p < .001), respectively, and 199.9 +/- 92.8 versus 111.9 +/- 61.4 (p < .001), respectively, for vaginal hysterectomy. CONCLUSION: Vaginal manual morcellation is safe with a low risk of incidental malignancy. Variables that influence the decision for the vaginal approach may also affect malignancy risk and morcellation decisions. Thus, all patients undergoing vaginal or laparoscopic assisted vaginal hysterectomy should be counseled regarding incidental malignancy, risk of morcellation, and alternatives for intact specimen removal. PMID- 26802909 TI - Nonmalignant Sequelae of Unconfined Morcellation at Laparoscopic Hysterectomy or Myomectomy. AB - The objective of this study was to evaluate nonmalignant sequelae of unconfined morcellation at hysterectomy and myomectomy. We performed a systematic review following the PRISMA statement key words of "morcellation, uterine leiomyoma, uterine fibroid, laparoscopic myomectomy, laparoscopic total hysterectomy, and laparoscopic supracervical hysterectomy" and their combination. Fifty-one articles met the inclusion criteria: 11 articles were related to endometriosis, adenomyosis, and endometrial hyperplasia; 30 articles parasitic myoma; and 9 disseminated peritoneal leiomyomatosis (DPL) and 1 DPL and endometriosis. We found that laparoscopic hysterectomy or myomectomy with unconfined morcellation is associated with the risk of iatrogenic endometriosis (1.4%), adenomyosis (0.57%), parasitic myoma (0.9%), and rarely DPL. Our study showed that benign sequelae of uterine or myoma morcellation could be found in up to 1% of cases. This is much higher than the prevalence of uterine sarcoma after morcellation. Benign conditions have less consequences than malignancy, yet they are more common and might require another operation. Accordingly, if morcellation is required, confined morcellation should be considered. PMID- 26802911 TI - What's your poison? Neurobehavioural consequences of exposure to industrial, agricultural and environmental chemicals. PMID- 26802910 TI - PCA-based groupwise image registration for quantitative MRI. AB - Quantitative magnetic resonance imaging (qMRI) is a technique for estimating quantitative tissue properties, such as the T1 and T2 relaxation times, apparent diffusion coefficient (ADC), and various perfusion measures. This estimation is achieved by acquiring multiple images with different acquisition parameters (or at multiple time points after injection of a contrast agent) and by fitting a qMRI signal model to the image intensities. Image registration is often necessary to compensate for misalignments due to subject motion and/or geometric distortions caused by the acquisition. However, large differences in image appearance make accurate image registration challenging. In this work, we propose a groupwise image registration method for compensating misalignment in qMRI. The groupwise formulation of the method eliminates the requirement of choosing a reference image, thus avoiding a registration bias. The method minimizes a cost function that is based on principal component analysis (PCA), exploiting the fact that intensity changes in qMRI can be described by a low-dimensional signal model, but not requiring knowledge on the specific acquisition model. The method was evaluated on 4D CT data of the lungs, and both real and synthetic images of five different qMRI applications: T1 mapping in a porcine heart, combined T1 and T2 mapping in carotid arteries, ADC mapping in the abdomen, diffusion tensor mapping in the brain, and dynamic contrast-enhanced mapping in the abdomen. Each application is based on a different acquisition model. The method is compared to a mutual information-based pairwise registration method and four other state-of the-art groupwise registration methods. Registration accuracy is evaluated in terms of the precision of the estimated qMRI parameters, overlap of segmented structures, distance between corresponding landmarks, and smoothness of the deformation. In all qMRI applications the proposed method performed better than or equally well as competing methods, while avoiding the need to choose a reference image. It is also shown that the results of the conventional pairwise approach do depend on the choice of this reference image. We therefore conclude that our groupwise registration method with a similarity measure based on PCA is the preferred technique for compensating misalignments in qMRI. PMID- 26802913 TI - Association Report: Changing the Conversation; How Every Pharmacist Can Help Decrease Medication Errors and Sleep Better at Night; Policy, Community Service at Forefront of Student Pharmacists' Patient Safety Activity. PMID- 26802912 TI - Remission And relapse of myasthenia gravis on long-term azathioprine: An ambispective study. AB - INTRODUCTION: Azathioprine (AZA) is commonly used in myasthenia gravis (MG). Treatment may be prolonged, entailing significant risks and avoidable costs. METHODS: We reviewed remission, relapse, and side-effect profiles in MG patients on AZA during treatment and after tapering off. We conducted an ambispective study and analyzed remission, relapse rates, and side-effect profiles in 117 MG patients on AZA. RESULTS: Thirty-nine patients (33.3%) achieved remission, and 36 (30.8%) achieved complete stable remission (CSR), with a 33% relapse rate. No AZA side effects were seen in 95 (81%) patients. Only duration of disease of >10 years (odds ratio 9.5, 95% confidence interval 2.4-36.9, P = 0.001) was significantly associated with remission. CONCLUSIONS: AZA is well tolerated by MG patients, and about 30% go into CSR on long-term AZA. Muscle Nerve, 2016 Muscle Nerve 54: 405-412, 2016. PMID- 26802914 TI - JAPhA and Elsevier: A new beginning. PMID- 26802915 TI - Effectiveness of a pharmacist-physician collaborative program to manage influenza like illness. AB - OBJECTIVES: To examine the effectiveness of collaborative physician-community pharmacist programs to treat influenza-like illness (ILI) with respect to clinical outcomes and health care utilization. DESIGN: Prospective multicenter cohort study. SETTING: Fifty-five pharmacies in Michigan, Minnesota, and Nebraska. PATIENTS: Adult patients presenting to the pharmacy with ILI during the 2013-14 influenza season (October 1, 2013 to May 30, 2014). INTERVENTION: Pharmacists screened adult patients presenting with ILI, completed a brief physical assessment, performed a point-of-care rapid influenza diagnostic test (RIDT), and provided appropriate referral or treatment per an established collaborative practice agreement (CPA) with a licensed prescriber. Pharmacists followed-up with patients 24 to 48 hours after the encounter to assess patient status and possible need for further intervention. MAIN OUTCOME MEASURES: Number of patients screened, tested, and treated for influenza. RESULTS: Of the 121 patients screened, 45 (37%) were excluded and referred to their primary care provider or an urgent care facility for management. Of the 75 patients (62%) eligible for participation, 8 (11%) had a positive RIDT and were managed according to the CPA. Of the patients tested, 34.6% had no primary care physician and 38.7% visited the pharmacy outside of normal office hours. Only 3% of patients reported feeling worse at follow-up. CONCLUSION: This study describes a physician-pharmacist collaborative model for treating ILI. Using an evidence based CPA, pharmacists were able to provide timely treatment to patients with and without influenza. PMID- 26802916 TI - Impact of a medication therapy management intervention targeting medications associated with falling: Results of a pilot study. AB - BACKGROUND: The use of fall risk-increasing drugs (FRIDs) by older adults is one factor associated with falling, and FRID use is common among older adults. A targeted medication therapy management intervention focused on FRID use that included prescription and over-the-counter (OTC) medications, along with follow up telephone calls was designed. OBJECTIVE: The purpose of this pilot study was to examine preliminary effects of a medication therapy management (MTM) intervention focused on FRIDs provided by a community pharmacist to older adults. DESIGN: Randomized, controlled trial. SETTING: One community pharmacy. PARTICIPANTS: Eighty older adults who completed a fall prevention workshop. MAIN OUTCOME MEASURES: The main outcome measures were the rate of discontinuing FRIDs, the proportion of older adults falling, and the number of falls. A secondary outcome was the acceptance rate of medication recommendations by patients and prescribers. RESULTS: Thirty-eight older adults received the targeted MTM intervention. Of the 31 older adults using a FRID, a larger proportion in the intervention group had FRID use modified relative to controls (77% and 28%, respectively; P < 0.05). There were no significant changes between the study groups in the risk and rate of falling. Medication recommendations in the intervention group had a 75% acceptance rate by patients and prescribers. CONCLUSION: A targeted MTM intervention provided by a community pharmacist and focused on FRID use among older adults was effective in modifying FRID use. This result supports the preliminary conclusion that community pharmacists can play an important role in modifying FRID use among older adults. PMID- 26802917 TI - Impact of the RxVaccinate program for pharmacy-based pneumococcal immunization: A cluster-randomized controlled trial. AB - OBJECTIVES: To evaluate the impact of the RxVaccinate program on the structure, process, and outcome measures and to assess team leaders' perceptions of the program. DESIGN: Cluster-randomized experimental design. SETTING: Community pharmacies. PARTICIPANTS: Community pharmacists. INTERVENTIONS: The RxVaccinate program consisted of (a) two self-directed training webinars and practice development and implementation tools and (b) expert and peer coaching sessions through an in-person 4-hour workshop and optional e-community and monthly teleconferences. One group received only the self-directed training (self directed learning group), and the other group received both self-directed training and coaching sessions (coaching group). MAIN OUTCOME MEASURES: Both groups provided data on (a) completion of structure and process indicators at 3, 6, and 9 months after the in-person workshop, (b) number of pneumococcal vaccinations administered in pharmacy during the 12-month period preceding and following the in-person coaching workshop, and (c) team leaders' perceptions of the RxVaccinate program. RESULTS: Greater proportions of pharmacies in the coaching group completed structure and process indicators than pharmacies in the self-directed learning group. Both groups showed an increase in the number of pneumococcal vaccinations administered (P < 0.001). The increase was significantly greater among pharmacies in the coaching group than among pharmacies in the self-directed training (P = 0.032). Team leaders in both groups were generally satisfied with the RxVaccinate program. CONCLUSION: Although significant increases in the number of pharmacist-administered pneumococcal vaccinations were observed in both groups, the increase was greater in the group receiving both self-directed training and expert and peer coaching than the group without the coaching strategy. This could be because pharmacies in the coaching group were more likely to complete structure and process indicators than their counterparts. Future studies should examine key structure and process indicators affecting the success of pneumococcal vaccinations. PMID- 26802918 TI - Determining the accuracy of open-access databases for identifying commonly prescribed oral medications. AB - OBJECTIVES: To compare the accuracy of open-access medication identification databases in identifying commonly prescribed oral tablets and capsules. METHODS: We compiled a dataset from the most frequently prescribed medications in 2012 and 2013 by total prescription volume. Imprints for the medications were obtained from the Food and Drug Administration label information accessed via the National Library of Medicine's (NLM) DailyMed. The imprints were used to determine if the correct medication could be identified in the open-access medication identification databases Drugs.com, Healthline, NLM's Pillbox, RxList, and WebMD by means of the imprints alone. A general web search using the imprints as key words via Google search engine was also conducted to mimic the lay public's approach to identifying an unknown medication. RESULTS: Database accuracy of search results ranged from 26.5% to 89.27% with the NLM Pillbox having the highest accuracy when using tablet/capsule imprint information alone. The secondary web search with the use of the Google search engine yielded 75.7% accuracy in using imprints as search terms to identify websites leading to the appropriate drugs. Drugs.com was listed as the first site for the majority of Google searches and was 86.44% accurate. CONCLUSION: Open-access databases are available to help identify oral tablets and capsules and they have a relatively high success rate of identifying commonly prescribed medications. However no database is 100% accurate, which means that the risk involved with patients identifying their own medications is substantial. Patients should be highly encouraged by all health care practitioners to consult their pharmacist or primary health care provider to prevent misidentification and subsequent misadministration. PMID- 26802919 TI - Unused medications and disposal patterns at home: Findings from a Medicare patient survey and claims data. AB - OBJECTIVE: To examine what medications are most frequently left unused by patients, how much is left unused, and how these medications are disposed of among Medicare beneficiaries. DESIGN: Secondary data analysis combining insurance claims and telephone survey data of Medicare Advantage members. SETTING: Regional health plan in Central Pennsylvania. PARTICIPANTS: Seven hundred twenty-one Medicare Advantage members who had Part D coverage through the plan as of December 31, 2013, and completed the telephone survey in May 2014. INTERVENTION: Telephone survey conducted by a survey research center. MAIN OUTCOME MEASURE: Member survey response. RESULTS: Of the 2,994 medications in the dataset, 247 (8%) were reported being left unused by patients. Of the 247, the most common medications were those for pain (15%), hypertension (14%), antibiotics (11%), and psychiatric disorders (9%). Approximately 15% of unused medications were controlled substances. The reasons for being unused varied by drug type. For example, for pain medications, adverse effects and overprescribing were the most commonly cited reasons; for hypertension medications, "dosage changed by doctor" was the most common reason. Most commonly, unused portions accounted for approximately 25% to 50% of the unused medications identified by patients. Approximately 11% of unused medication was disposed of via drug take-back programs, whereas the majority was kept in a cabinet (55%), thrown in the trash (14%), or flushed down the toilet (9%). CONCLUSION: A lack of patient adherence alone does not explain unused medications and their improper disposal. Community level interventions designed to improve prescription efficiency and patient awareness of appropriate disposal methods-particularly of controlled substances are necessary to reduce the potentially harmful effects of improper disposal of unused medications. PMID- 26802920 TI - The adherence impact of a program offering specialty pharmacy services to patients using retail pharmacies. AB - BACKGROUND: A new service model integrates the specialty pharmacy's comprehensive service with the retail pharmacy's patient contact, giving patients options for medication delivery to home, pharmacy, or doctor's office. OBJECTIVE: Evaluate the impact of the new service model on medication adherence. DESIGN: Retrospective cohort study SETTINGS: One hundred fifteen CVS retail stores in Philadelphia participated in a pilot from May 2012 to October 2013, and 115 matched CVS retail stores from around the nation served as controls. PATIENTS: All eligible patients from the intervention and control stores received specialty medications through CVS retail pharmacies prior to implementation of the new service model. INTERVENTION: The intervention patients were transitioned from retail pharmacy service to the specialty pharmacy with delivery options. The control patients received standard retail pharmacy services. MAIN OUTCOME MEASURES: Proportion of days covered and first fill persistence were tracked for 12 months before and after program implementation. RESULTS: Under the new service model, 228 patients new to therapy in the post period had a 17.5% increase in the rate of obtaining a second fill as compared to matched controls. Patients on therapy in both the pre- and the post-periods had a pre-post increase of 6.6% in average adherence rates and a pre-post increase of 10.8% in optimal adherence rates as compared to 326 matched controls. CONCLUSION: The study demonstrated significant improvement in both adherence to therapy and first-fill persistence among patients in the new service model integrating specialty pharmacy's comprehensive services with the retail pharmacy's patient contact and medication delivery choices. PMID- 26802921 TI - Evaluating the impact of a pediatric weight-based dosing procedure in outpatient pharmacy. AB - OBJECTIVES: To describe the percentage of pediatric outpatient pharmacy prescriptions with inappropriate prescribing identified by a pharmacist that resulted in a change to the prescription. Secondary objectives include describing types of inappropriate prescribing errors, prevalence of Institute of Safe Medication Practices high-alert medications, patient demographics, prescriber origin, and prescription origin. METHODS: This retrospective outpatient prescription record review was approved by an institutional review board and performed at an outpatient pharmacy located in an academic teaching hospital. The study reviewed pediatric outpatient prescriptions for a 6-month period. Prescriptions with prescribing errors were identified from pediatric prescriptions sent to the problem queue and documented with appropriate pharmacist notes. RESULTS: This study demonstrated the impact of a dose checking procedure and pharmacist interventions on pediatric prescriptions. Initial results show that 3% of all pediatric prescriptions required a pharmacist intervention. Of these prescriptions, 50% resulted in a change to the original prescription. CONCLUSION: Weight-based dose checking in a pediatric outpatient pharmacy proactively prevents potential adverse events among the pediatric population. Despite this study's limitations, we believe that a pediatric dose checking procedure in community pharmacies will reduce adverse events. Further study is warranted in this field. PMID- 26802922 TI - Estimating the cost of unclaimed electronic prescriptions at an independent pharmacy. AB - OBJECTIVES: The increasing rate of e-prescribing is associated with a significant number of unclaimed prescriptions. The costs of unclaimed e-prescriptions could create an unwanted burden on community pharmacy practices. The objective of this study was to calculate the rate and costs of filled but unclaimed e-prescriptions at an independent pharmacy. METHODS: This study was performed at a rural independent pharmacy in a Midwestern state. The rate and costs of the unclaimed e prescriptions were determined by collecting information about all unclaimed e prescriptions for a 6-month period from August 2013 to January 2014. The costs of unclaimed prescriptions included those expenses incurred to prepare the prescription, contact the patient, and return the unclaimed prescription to inventory. Two sensitivity analyses were conducted. RESULTS: The total cost of 147 unclaimed e-prescriptions equaled $3,677.70 for the study period. Thus, the monthly cost of unclaimed e-prescriptions was $612.92 and the average cost of each unclaimed prescription was $25.02. The sensitivity analyses showed that using a technician to perform prescription return tasks reduced average costs to $19.33 and that using a state Medicaid cost of dispensing resulted in average costs of $18.54 per prescription. The rate of unclaimed e-prescriptions was 0.82%. CONCLUSION: The percentage of unclaimed e-prescriptions in this pharmacy was less than 1%. In addition to increased cost, unclaimed e-prescriptions add inefficiency to the work flow of the pharmacy staff, which can limit the time that they are available for performing revenue-generating activities. Adjustments to work flow and insurer policies could help to reduce the burden of unclaimed e prescriptions. PMID- 26802923 TI - Mobile application features sought after by patients of a regional grocery store chain pharmacy. AB - OBJECTIVE: To determine the mobile application features for pharmacy services sought after by patients of a grocery store chain pharmacy. METHODS: Key informant interviews were conducted at 5 Giant Eagle Pharmacy locations in the Greater Pittsburgh area. Patients older than 35 years who receive 1 prescription monthly from Giant Eagle and use a smartphone daily were eligible to participate. Interviews were audio recorded, and transcripts underwent thematic analysis. RESULTS: Twenty-four interviews were conducted from February to March 2014. The average age of participants was 51 years. About one-half of the participants (46%) were currently using mobile applications to manage their health. Three themes emerged regarding patients' desires for a mobile application: design that fosters an improved, convenient pharmacy experience; features that support the self-management of health; and design that increases personalized, timely access to pharmacists. CONCLUSION: This qualitative analysis revealed that pharmacy patients desire a mobile application that improves the convenience of their pharmacy experience, enables them to self-manage their health, and increases their access to their pharmacist. PMID- 26802924 TI - Pharmacist home visits: A 1-year experience from a community pharmacy. AB - OBJECTIVE: To provide experience on the methods and costs for delivering a large scale community pharmacist home visit service. SETTING: Independent urban community pharmacy, Buffalo, NY. PRACTICE DESCRIPTION: Mobile Pharmacy Solutions provides traditional community pharmacy walk-in service and a suite of clinically oriented services, including outbound adherence calls linked to home delivery, payment planning, medication refill synchronization, adherence packaging, and pharmacist home visits. Pharmacist daily staffing included three dispensing pharmacists, one residency-trained pharmacist, and two postgraduate year 1 community pharmacy residents. PRACTICE INNOVATION: A large-scale community pharmacy home visit service delivered over a 1-year period. EVALUATION: Pharmacist time and cost to administer the home visit service as well as home visit request sources and description of patient demographics. RESULTS: A total of 172 visits were conducted (137 initial, 35 follow-up). Patients who received a home visit averaged 9.8 +/- 5.2 medications and 3.0 +/- 1.6 chronic disease states. On average, a home visit required 2.0 +/- 0.8 hours, which included travel time. The percentages of visits completed by pharmacists and residents were 60% and 40%, respectively. The amounts of time to complete a visit were similar. Average home visit cost including pharmacist time and travel was $119 ($147 for a pharmacist, $77 for a resident). CONCLUSION: In this community pharmacy-based home visit service, costs are an important factor, with each pharmacist visit requiring 2 hours to complete. This experience provides a blueprint and real-world perspective for community pharmacies endeavoring to implement a home visit service and sets a foundation for future prospective trials to evaluate the impact of the service on important indicators of health and cost. PMID- 26802925 TI - SafeMed: Using pharmacy technicians in a novel role as community health workers to improve transitions of care. AB - OBJECTIVES: To describe the design, implementation, and early experience of the SafeMed program, which uses certified pharmacy technicians in a novel expanded role as community health workers (CPhT-CHWs) to improve transitions of care. SETTING: A large nonprofit health care system serving the major medically underserved areas and geographic hotspots for readmissions in Memphis, TN. PRACTICE INNOVATION: The SafeMed program is a care transitions program with an emphasis on medication management designed to use low-cost health workers to improve transitions of care from hospital to home for superutilizing patients with multiple chronic conditions and polypharmacy. EVALUATION: CPhT-CHWs were given primary responsibility for patient outreach after hospital discharge with the use of home visits and telephone follow-up. SafeMed program CPhT-CHWs served as pharmacist extenders, obtaining medication histories, assisting in medication reconciliation and identification of potential drug therapy problems (DTPs), and reinforcing medication education previously provided by the pharmacist per protocol. RESULTS: CPhT-CHW training included patient communication skills, motivational interviewing, medication history taking, teach-back techniques, drug disposal practices, and basic disease management. Some CPhT-CHWs experienced difficulties adjusting to an expanded scope of practice. Nonetheless, once the Tennessee Board of Pharmacy affirmed that envisioned SafeMed CPhT-CHW roles were consistent with Board rules, additional responsibilities were added for CPhT-CHWs to enhance their effectiveness. Patient outreach teams including CPhT-CHWs achieved increases in home visit and telephone follow-up rates and were successful in helping identify potential DTPs. CONCLUSION: The early experience of the SafeMed program demonstrates that CPhT-CHWs are well suited for novel expanded roles to improve care transitions for superutilizing populations. CPhT CHWs can identify and report potential DTPs to the pharmacist to help target medication therapy management. Critical success factors include strong CPhT-CHW patient-centered communication skills and strong pharmacist champions. In collaboration with state pharmacy boards and pharmacist associations, the SafeMed CPhT-CHW model can be successfully scaled to serve superutilizing patients throughout the country. PMID- 26802926 TI - Preventing infant mortality: Pharmacists' call to action. AB - OBJECTIVE: To highlight ways in which pharmacists can influence the infant mortality rate. SUMMARY: The infant mortality rate in the United States is higher than in many other industrialized nations. Because pharmacists are accessible and knowledgeable health care professionals, there are multiple opportunities for pharmacist intervention from the preconception to the postpartum periods that can affect the leading causes of infant death. Specifically, areas of focus for pharmacists' direct patient care activities can include family planning, substance use, folic acid, drug information, maternal disease management, maternal medication management, infant medication management, safe sleep, breastfeeding, and vaccines. In addition, there are opportunities for pharmacists to influence infant mortality through clinical-community linkages, research, and advocacy. CONCLUSIONS: Through clinical-community linkages and direct patient care, pharmacists can work toward reducing infant mortality in their communities. PMID- 26802927 TI - Journal of the American Pharmacists Association Guidelines for Authors. PMID- 26802928 TI - High-dose influenza vaccine in older adults. PMID- 26802930 TI - Pharmacists entering "a brave new world". PMID- 26802929 TI - Ceftazidime pentahydrate/avibactam sodium, Isavuconazonium sulfate, and Daclatasvir dihydrochloride. PMID- 26802931 TI - The Expression of IL-21 Is Promoted by MEKK4 in Malignant T Cells and Associated with Increased Progression Risk in Cutaneous T-Cell Lymphoma. PMID- 26802932 TI - Dyschromatosis Symmetrica Hereditaria and Aicardi-Goutieres Syndrome 6 Are Phenotypic Variants Caused by ADAR1 Mutations. PMID- 26802933 TI - Histone H3K27 Demethylase JMJD3 in Cooperation with NF-kappaB Regulates Keratinocyte Wound Healing. AB - Histone H3K27me3 demethylase JMJD3 has been shown to be involved in keratinocyte differentiation and wound healing. However, the exact molecular mechanism underlying JMJD3-mediated keratinocyte wound healing has not been fully elucidated. In this study, we report on the biological function of JMJD3 in keratinocyte wound healing using in vitro cell and in vivo animal models. Our results indicate that JMJD3 up-regulation and NF-kappaB activation occur in the region of the wound edge during keratinocyte wound healing. We also found that JMJD3 interacts with NF-kappaB, resulting in increased expression of the inflammatory, matrix metalloproteinase, and growth factor genes via demethylation of H3K27me3 at the gene promoters. Consistently, inactivation of JMJD3 or NF kappaB resulted in aberrant keratinocyte wound healing. Our study suggests that regulation of JMJD3 may provide a new therapeutic intervention for treating the chronic skin wound. PMID- 26802934 TI - Size resolved metal distribution in the PM matter of the city of Turin (Italy). AB - A work on the characterization of the air quality in the city of Turin was carried out in different sampling periods, reflecting early autumn and winter conditions, including a snow episode during the early 2012 European cold wave. The concentrations of 13 elements in eight size fractions of the aerosol were determined using inductively coupled plasma-mass spectrometry. The collection was carried out with a Andersen MkII cascade impactor. The size distribution of elements allowed the identification of three main behavioural types: (a) elements associated with coarse particles (Cd, Cr, Cu, Fe, Mn, Mo and Sn); (b) elements found within fine particles (As, Co, Pb and V) and (c) elements spread throughout the entire size range (Ni and Zn). Principal Component Analysis allowed to examine the relationships between the inorganic elements and to infer about their origin. Chemometric investigation and assessment of similarity in the distribution led to similar conclusions on the sources. The concentration of gaseous trace pollutants (O3, NOx and VOCs) was determined. The concentrations of these pollutants are scarcely correlated with the metal contents of all the size classes of the PM. The differences found in the O3, NO2 and VOCs levels of the two winter campaigns due to the high photochemical reactivity in the period after the snow episode, do not reflect in differences in the metals distribution in the PM. Since PM metals, NOx and VOC have common sources, this behaviour is due to relevant differences in the transformation and deposition processes. PMID- 26802936 TI - Translating plasma and whole blood fatty acid compositional data into the sum of eicosapentaenoic and docosahexaenoic acid in erythrocytes. AB - Specific blood levels of eicosapentaenoic plus docosahexaenoic acid (EPA+DHA, wt% of total) in erythrocytes or "the omega-3 index" have been recommended for cardio protection, but fatty acids are often measured in different blood fractions. The ability to estimate the % of EPA+DHA in erythrocytes from the fatty acid composition of other blood fractions would enable clinical assessments of omega-3 status when erythrocyte fractions are not available and increase the ability to compare blood levels of omega-3 fatty acids across clinical studies. The fatty acid composition of baseline plasma, erythrocytes and whole blood samples from participants (n=1104) in a prospective, multicenter study examining acute coronary syndrome were determined. The ability to predict the % of EPA+DHA in erythrocytes from other blood fractions were examined using bivariate and multiple linear regression modelling. Concordance analysis was also used to compare the actual erythrocytes EPA+DHA values to values estimated from other blood fractions. EPA+DHA in erythrocytes was significantly (p<0.001) correlated EPA+DHA in plasma (r(2)=0.54) and whole blood (r(2)=0.79). Using multiple linear regression to predict EPA+DHA in erythrocytes resulted in stronger coefficients of determination in both plasma (R(2)=0.70) and whole blood (R(2)=0.84). Concordance analyses indicated agreement between actual and estimated EPA+DHA in erythrocytes, although estimating from plasma fatty acids appears to require translation by categorization rather than by translation as continuous data. This study shows that the fatty acid composition of different blood fractions can be used to estimate erythrocyte EPA+DHA in a population with acute coronary syndrome. PMID- 26802935 TI - The Toll-like receptor 4-activated neuroprotective microglia subpopulation survives via granulocyte macrophage colony-stimulating factor and JAK2/STAT5 signaling. AB - Toll-like receptor (TLR) 4 mediates inflammation and is also known to trigger apoptosis in microglia. Our time-lapse observations showed that lipopolysaccharide (LPS) stimulation induced rapid death in primary cultures of rat microglia, while a portion of the microglia escaped from death and survived for much longer than 2 days, in which time, all of the control cells had died. However, it remains unclear how the LPS-stimulated microglia subpopulation could continue to survive in the absence of any supplied growth factors. In the present study, to clarify the mechanism underlying the LPS-stimulated survival, we investigated whether microglia could produce their own survival factors in response to LPS, focusing on macrophage colony-stimulating factor (M-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin (IL) 34, which are mainly supplied by astrocytes or neurons. The LPS-stimulated microglia drastically induced the expression of the GM-CSF mRNA and protein, while M-CSF and IL-34 levels were unchanged. The surviving microglia also significantly upregulated the expression of GM-CSF receptor (GM-CSFR) mRNA without affecting M-CSFR. As for the GM-CSFR downstream signal, LPS resulted in the phosphorylation of STAT5 and its translocation to the nucleus in the surviving microglia. Moreover, a specific JAK2 inhibitor, NVP-BSK805, suppressed STAT5 phosphorylation and microglia survival in response to LPS, indicating a critical role of the JAK2/STAT5 pathway in this survival mechanism. Together, these results suggest that a subpopulation of TLR4-activated microglia may survive by producing GM-CSF and up-regulating GM-CSFR. This autocrine GM-CSF pathway may activate the JAK2/STAT5 signaling pathway, which controls the transcription of survival-related genes. Finally, these surviving microglia may have neuroprotective functions because the neurons remained viable in co-cultures with these microglia. PMID- 26802937 TI - Docosahexaenoic acid prevented tumor necrosis factor alpha-induced endothelial dysfunction and senescence. AB - We investigated how docosahexaenoic acid (DHA) regulated tumor necrosis factor alpha (TNF-alpha)-induced senescence and dysfunction in endothelial cells (EC). We used RT-PCR to examine the expression of several genes related to senescence and dysfunction in EC. TNF-alpha-induced p21 protein levels were investigated by Western blot (WB) and fluorescence antibody techniques. TNF-alpha induced the senescence marker beta-galactosidase and the expression of several senescence and endothelial dysfunction-related genes, e.g., CDKN1A, SHC1 and GLB1. DHA attenuated TNF-alpha-induced senescence-related gene expression and p21 protein expression. DHA attenuated TNF-alpha-induced gene expression related to dysfunction of EC, such as plasminogen activator inhibitor 1 (SERPINE1), lectin like oxidized low-density lipoprotein receptor-1 (OLR1), thromboxane A2 receptor (TXA2R) and p38 MAPK (MAPK14). DHA reversed the TNF-alpha-mediated reduction of endothelial nitric oxide synthase (NOS3) gene expression. TNF-alpha-mediated upregulation of these genes was inhibited by allopurinol and apocynin. These results indicated that DHA regulated the expression of several genes that are associated with senescence and dysfunction of EC. PMID- 26802938 TI - Brown but not white adipose cells synthesize omega-3 docosahexaenoic acid in culture. AB - Adipose tissue is a complex endocrine organ which coordinates several crucial biological functions including fatty acid metabolism, glucose metabolism, energy homeostasis, and immune function. Brown adipose tissue (BAT) is most abundant in young infants during the brain growth spurt when demands for omega-3 docosahexaenoic acid (DHA, 22:6n-3) is greatest for brain structure. Our aim was to characterize relative biosynthesis of omega-3 long chain polyunsaturated fatty acids (LCPUFA) from precursors in cultured white (WAT) and brown (BAT) cells and study relevant gene expression. Mouse WAT and BAT cells were grown in regular DMEM media to confluence, and differentiation was induced. At days 0 and 8 cells were treated with albumin bound d5-18:3n-3 (d5-ALA) and analyzed 24h later. d5 ALA increased cellular eicosapentaenoic acid (EPA, 20:5n-3) and docosapentaenoic acid (DPA, 22:5n-3) in undifferentiated BAT cells, whereas differentiated BAT cells accumulated 20:4n-3, EPA and DPA. DHA as a fraction of total omega-3 LCPUFA was greatest in differentiated BAT cells compared to undifferentiated cells. Undifferentiated WAT cells accumulated EPA, whereas differentiated cells accumulated DPA. WAT accumulated trace newly synthesized DHA. Zic1 a classical brown marker and Prdm16 a key driver of brown fat cell fate are expressed only in BAT cells. Ppargc1a is 15 fold higher in differentiated BAT cells. We conclude that in differentiated adipose cells accumulating fat, BAT cells but not WAT cells synthesize DHA, supporting the hypothesis that BAT is a net producer of DHA. PMID- 26802939 TI - Supplementation of maternal omega-3 fatty acids to pregnancy induced hypertension Wistar rats improves IL10 and VEGF levels. AB - OBJECTIVES: Our recent study demonstrates the beneficial effect of a combined supplementation of vitamin B12, folic acid, and docosahexaenoic acid in reducing the severity of pregnancy induced hypertension (PIH). It is also known to be associated with angiogenic imbalance and inflammation. The current study examines whether the individual/combined supplementation of folic acid, vitamin B12 and omega-3 fatty acid during pregnancy can ameliorate the inflammatory markers and restore the angiogenic balance in a rat model of PIH. MATERIALS AND METHODS: There were total of six groups, control and five treatment groups: PIH Induced; PIH+vitamin B12; PIH+folic acid; PIH+Omega-3 fatty acids and PIH+combined micronutrient supplementation (vitamin B12+folic acid+omega-3 fatty acids). Hypertension during pregnancy was induced using L- Nitroarginine methylester (L NAME; 50mg/kg body weight/day). Dams were dissected at d20 of gestation and placental tissues were collected for further analysis. RESULTS: Animals from the PIH induced group demonstrated lower (p<0.01 for both) IL-10 and VEGF levels as compared to control. However, PIH induction did not alter the protein levels of eNOS, IL-6, Flt and mRNA levels of VEGF and VEGFR-1/ Flt-1. Individual micronutrient supplementation of vitamin B12 and folate did not offer benefit. In contrast individual omega-3 fatty acid as well as combined micronutrient supplementation showed IL-10 and VEGF levels comparable to that of control. CONCLUSION: Omega 3 fatty acid supplementation plays a key role in reducing inflammation in pregnancy induced hypertension. PMID- 26802940 TI - The stability of blood fatty acids during storage and potential mechanisms of degradation: A review. AB - Fatty acids in blood samples, particularly polyunsaturated fatty acids (PUFAs), are susceptible to degradation through peroxidation reactions during long-term storage. Storage of blood samples is necessary in almost all studies and is crucial for larger clinical studies and in field research settings where it is not plausible for analytical infrastructure. Despite this, PUFA stability during blood storage is often overlooked. This review introduces and discusses lipid peroxidation and popular strategies employed to prevent or minimize peroxidation reactions during fatty acid analysis. Further, an in-depth examination of fatty acid stability during storage of blood is discussed in detail for all blood fractions including plasma/serum, erythrocytes and whole blood stored both in cryovials and on chromatography paper before discussing the associated mechanisms of degradation during storage. To our knowledge this is the first review of its kind and will provide researchers with the necessary information to confidently store blood samples for fatty acid analysis. PMID- 26802941 TI - Apigenin inhibits COX-2, PGE2, and EP1 and also initiates terminal differentiation in the epidermis of tumor bearing mice. AB - Non-melanoma skin cancer (NMSC) is the most prevalent cancer in the United States. NMSC overexpresses cyclooxygenase-2 (COX-2). COX-2 synthesizes prostaglandins such as PGE2 which promote proliferation and tumorigenesis by engaging G-protein-coupled prostaglandin E receptors (EP). Apigenin is a bioflavonoid that blocks mouse skin tumorigenesis induced by the chemical carcinogens, 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol 13-acetate (TPA). However, the effect of apigenin on the COX-2 pathway has not been examined in the DMBA/TPA skin tumor model. In the present study, apigenin decreased tumor multiplicity and incidence in DMBA/TPA-treated SKH-1 mice. Analysis of the non-tumor epidermis revealed that apigenin reduced COX-2, PGE2, EP1, and EP2 synthesis and also increased terminal differentiation. In contrast, apigenin did not inhibit the COX-2 pathway or promote terminal differentiation in the tumors. Since fewer tumors developed in apigenin-treated animals which contained reduced epidermal COX-2 levels, our data suggest that apigenin may avert skin tumor development by blocking COX-2. PMID- 26802942 TI - Structural attributes of the temporal lobe predict face recognition ability in youth. AB - The face recognition ability varies across individuals. However, it remains elusive how brain anatomical structure is related to the face recognition ability in healthy subjects. In this study, we adopted voxel-based morphometry analysis and machine learning approach to investigate the neural basis of individual face recognition ability using anatomical magnetic resonance imaging. We demonstrated that the gray matter volume (GMV) of the right ventral anterior temporal lobe (vATL), an area sensitive to face identity, is significant positively correlated with the subject's face recognition ability which was measured by the Cambridge face memory test (CFMT) score. Furthermore, the predictive model established by the balanced cross-validation combined with linear regression method revealed that the right vATL GMV can predict subjects' face ability. However, the subjects' Cambridge face memory test scores cannot be predicted by the GMV of the face processing network core brain regions including the right occipital face area (OFA) and the right face fusion area (FFA). Our results suggest that the right vATL may play an important role in face recognition and might provide insight into the neural mechanisms underlying face recognition deficits in patients with pathophysiological conditions such as prosopagnosia. PMID- 26802943 TI - Giant schwannoma of the medial plantar nerve. AB - In this article the authors present an exceptionally rare case of giant schwannoma of the foot in a 23 year old male. This article demonstrates the key principles of investigation and management of such cases as conducted by a regional sarcoma centre. PMID- 26802944 TI - Current concepts of Charcot foot in diabetic patients. AB - The Charcot foot is an uncommon complication of neuropathy in diabetes. It is a disabling and devastating condition. The etiology of the Charcot foot is unknown, but it is characterized by acute inflammation with collapse of the foot and/or the ankle. Although the cause of this potentially debilitating condition is not known, it is generally accepted that the components of neuropathy that lead to foot complications must exist. When it is not detected early, a severe deformity will result in a secondary ulceration, infection, and amputation. Immobilization in the early stages is the key for success, but severe deformity may still develop. When severe deformity is present, bracing may be attempted but often patients will need surgical intervention. Good success has been shown with internal and external fixation. In patients with concomitant osteomyelitis, severe deformity, and/or soft tissue infection, a high amputation may be the best treatment of choice. PMID- 26802945 TI - Prospective randomized clinical trial of aggressive rehabilitation after acute Achilles tendon ruptures repaired with Dresden technique. AB - BACKGROUND: Rupture of the Achilles tendon is a common injury during working years. Aggressive rehabilitation may provide better outcomes, but also a greater chance of re-rupture. OBJECTIVE: To determine if aggressive rehabilitation has better clinical outcomes for Achilles tendon function, Triceps surae function, one-leg heel rise capacity and lower complication rate during twelve weeks after percutaneous Achilles tendon repair compared to conventional rehabilitation. DESIGN: Randomized controlled trial. METHOD: Thirty-nine patients were prospectively randomized. The aggressive group (n=20, 41.4 +/- 8.3 years) received rehabilitation from the first day after surgery. The conventional group (n=19, 41.7 +/- 10.7 years) rested for 28 days, before rehabilitation started. The statistical parameters were the Achilles tendon rupture score (ATRS), verbal pain scale, time to return to work, pain medication consumption, Achilles tendon strength, dorsiflexion range of motion (RoM), injured-leg calf circumference, calf circumference difference, one-leg heel rise repetition and difference, re rupture rate, strength deficit rate, and other complication rates. Mixed-ANOVA and Bonferroni's post hoc test were performed for multiple comparisons. Student's t-test was performed for parameters measured on the 12th week. RESULTS: The aggressive group with respect to the conventional group had a higher ATRS; lower verbal pain score; lower pain medication consumption; early return to work; higher Achilles tendon strength; higher one-leg heel rise repetitions; and lower one-leg heel rise difference. The re-rupture rate was 5% and 5%, the strength deficit rate was 42% and 5%, and other complications rate was 11% and 15% in the conventional and aggressive group, respectively. CONCLUSION: Patients with Dresden repair and aggressive rehabilitation have better clinical outcomes, Achilles tendon function and one-leg heel rise capacity without increasing the postoperative complications rate after 12 weeks compared to rehabilitation with immobilization and non-weight-bearing during the first 28 days after surgery. PMID- 26802946 TI - Extracorporeal shockwave therapy (ESWT) for refractory Achilles tendinopathy: A prospective audit with 2-year follow up. AB - BACKGROUND: Achilles tendinopathy (AT) represents a triad of tendon pain, swelling and impaired performance. Extracorporeal shockwave therapy (ESWT) has been endorsed by the National Institute for Health and Care Excellence (NICE) for refractory AT. This audit investigates the long-term outcomes of patients treated with ESWT for refractory AT. METHODS: Forty-six patients treated with ESWT for AT between October 2010 and August 2011 completed visual analogue, satisfaction scores and functional assessment questionnaires over two years. Patients were subdivided into two groups depending on whether their AT was insertional (IAT) or non-insertional (NAT). RESULTS: Forty-six patients (mean age 58 years) completed all treatments and full 2 year follow up. There was significant improvement in pain at rest, on activity and of function within both NAT and IAT groups over the two-year period. Satisfaction scores were significant in the NAT group but not in the IAT group. CONCLUSIONS: ESWT appears to be of benefit in the long term improvement of pain at rest, on activity and functional outcome in patients with refractory AT. However, subjective patient opinion may not match the perceived clinical outcome observed in this audit in all patients and individuals should be counselled regarding this prior to treatment. PMID- 26802947 TI - Evaluation of dorsal Lisfranc ligament deformation with load using ultrasound imaging. AB - BACKGROUND: Research findings have linked dorsal Lisfranc ligament (dLL) rupture to complete Lisfranc ligament complex rupture; identifying deformation characteristics of the dorsal Lisfranc ligament alone may be helpful in diagnosing complete ligament rupture. The goal of the present study was to assess the deformation characteristics of the asymptomatic dLL using physiologically relevant stress/loads in a clinical setting and to discern normative dLL parameters. METHODS: Unilateral dLL measurements were taken from 50 healthy volunteers, using sonographic imaging under three different stress/load conditions. Stress/load was applied using the individuals' bodyweight (low seated; medium-bilaterally equal weight bearing in standing; and high-single leg standing). Digital images of the dLL captured using ultrasound were visualized to determine the dLL length. One-way repeated measures ANOVA was used to assess changes in the dLL length with load. RESULTS: The average dLL elongation, as percent resting length change, was 8.76% between seated and single leg standing positions. Most of the dLL elongation (6.26%) occurred between seated and bilateral standing. CONCLUSIONS: The deformation and role of the dorsal Lisfranc ligament can be observed using sonographic imaging resulting from physiological loading in the clinical setting. CLINICAL RELEVANCE: These deformation parameters can be used to generate normative data for diagnostic purposes. PMID- 26802948 TI - Endoscopic resection of subcutaneous lipoma and tumor-like lesion of the foot. AB - Open resection is the standard surgical treatment for subcutaneous lipoma. However, it may result in cosmetically non-desirable scars in case of large lesion. Endoscopic resection of subcutaneous lipoma and tumor-like lesions may result in better cosmetic result and patient satisfaction. The basis of the endoscopic technique is described. PMID- 26802949 TI - Chronic Achilles tendon rupture reconstructed using hamstring tendon autograft. AB - BACKGROUND: Chronic rupture of the Achilles tendon (delayed diagnosis of more than 4 weeks) can result in retraction of the tendon and inadequate healing. Direct repair may not be possible and augmentation methods are challenging when the defect exceeds 5-6 cm, especially if the distal stump is grossly tendinopathic. METHODS: We describe our method of Achilles tendon reconstruction with ipsilateral semitendinosis autograft and interference screw fixation in a patient with chronic rupture, a 9 cm defect and gross distal tendinopathy. RESULTS: Patient reported outcome measures consistently demonstrated improved health status at 12 months post surgery: MOXFQ-Index 38-25, EQ5D-5L 18-9, EQ VAS 70-90 and VISA-A 1-64. The patient was back to full daily function, could single leg heel raise and was gradually returning to sport. No complications or adverse events were recorded. CONCLUSION: Reconstruction of chronic tears of the Achilles tendon with large defects and gross tendinopathy using an ipsilateral semitendinosis autograft and interference screw fixation can achieve satisfactory improvements in patient reported outcomes up to 1 year post-surgery. PMID- 26802969 TI - Efficacy of an Electromechanical Gait Trainer Poststroke in Singapore: A Randomized Controlled Trial. AB - OBJECTIVE: To evaluate the longer-term effects of electromechanical gait trainers (GTs) combined with conventional physiotherapy on health status, function, and ambulation in people with subacute stroke in comparison with conventional physiotherapy given alone. DESIGN: Randomized controlled trial with intention-to treat analysis. SETTING: Community hospital in Singapore. PARTICIPANTS: Nonambulant individuals (N=106) recruited approximately 1 month poststroke. INTERVENTIONS: Both groups received 45 minutes of physiotherapy 6 times per week for 8 weeks as follows: the GT group received 20 minutes of GT training and 5 minutes of stance/gait training in contrast with 25 minutes of stance/gait training for the control group. Both groups completed 10 minutes of standing and 10 minutes of cycling. MAIN OUTCOME MEASURES: The primary outcome was the Functional Ambulation Category (FAC). Secondary outcomes were the Barthel Index (BI), gait speed and endurance, and Stroke Impact Scale (SIS). Measures were taken at baseline and 4, 8, 12, 24, and 48 weeks. RESULTS: Generalized linear model analysis showed significant improvement over time (independent of group) for the FAC, BI, and SIS physical and participation subscales. However, no significant group * time or group differences were observed for any of the outcome variables after generalized linear model analysis. CONCLUSIONS: The use of GTs combined with conventional physiotherapy can be as effective as conventional physiotherapy applied alone for people with subacute stroke. PMID- 26802970 TI - Circulating miR-34a levels correlate with age-related hearing loss in mice and humans. AB - Age-related hearing loss (AHL) is a progressive neurodegenerative disease that is largely silent in its initial stages. There is no sensitive blood biomarker for diagnosis or early detection of AHL. MicroRNAs (miRNAs or miRs) are abundant and highly stable in blood, and have been recently described as powerful circulating biomarkers in a wide range of diseases. In the present study, we identified concordant increases in miR-34a levels in the cochlea, auditory cortex, and plasma of C57BL/6 mice during aging. These increases were accompanied by elevated hearing thresholds and greater loss of hair cells. Levels of miR-34a targets, silent information regulator 1 (SIRT1), B-cell lymphoma-2 (Bcl-2), and E2F transcription factor 3 (E2F3), in the cochlea, auditory cortex, and plasma decreased with aging inversely to miR-34a. Moreover, plasma miR-34a levels were significantly higher in patients with AHL compared with controls who had normal hearing and had a receiver-operating characteristic curve that distinguished AHL patients from controls. However, SIRT1, Bcl-2, and E2F3 showed no correlation with AHL in humans. In summary, circulating miR-34a level may potentially serve as a useful biomarker for early detection of AHL. PMID- 26802971 TI - Transcriptional gene silencing of dopamine D3 receptor caused by let-7d mimics in immortalized renal proximal tubule cells of rats. AB - Transcriptional gene silencing (TGS) induced by synthetic exogenous short interfering RNAs (siRNAs) that are fully complementary to gene promoters has been demonstrated in mammalian cells. However, it remains unclear whether microRNAs (miRNAs), which are endogenous small regulatory RNAs, can also silence gene transcription. We investigated the regulation mechanism of let-7d on dopamine D3 receptor (DRD3) in immortalized renal proximal tubule (RPT) cells of rats, where let-7d has a predicted homologous target site within DRD3 promoter. We found that let-7d mimics repressed DRD3 expression at the transcription level in RPT cells. Let-7d induced DRD3 inhibition via DNA-methyltransferase 1 (DNMT1) and DNA methyltransferase 3b (DNMT3b) dependent DNA methylation and the inhibition could be abolished by 5'-aza-2'-deoxycytidine (5-aza-dc), a DNA methylation inhibitor. Let-7d induced DRD3 repression was associated with the recruitment of Argonaute 2 (AGO2) protein. Histone 3 lysine 9 dimethylation (H3K9me2) was involved in the let-7d induced DRD3 TGS, indicating the chromatin-level silencing. In conclusion, our results demonstrated that let-7d may induce DRD3 repression in a transcriptional manner by means of DNMTs dependent DNA methylation and histone modification. It is suggested that miRNAs may act as a transcriptional gene regulator via the recognition of the homologous target site within the gene promoter. PMID- 26802972 TI - Mitochondrial genome characterization of Tecia solanivora (Lepidoptera: Gelechiidae) and its phylogenetic relationship with other lepidopteran insects. AB - The complete mitogenome of the potato tuber moth Tecia solanivora (Lepidoptera: Gelechiidae) was sequenced, annotated, characterized and compared with 140 species of the order Lepidoptera. The circular genome is 15,251 bp, containing 37 genes (13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes and an A+T rich region). The gene arrangement was identical to other lepidopteran mitogenomes but different from the ancestral arrangement found in most insects for the tRNA-Met gene (A+T-region, tRNA-I, tRNA-Q, tRNA-M). The mitogenome of T. solanivora is highly A+T-biased (78.2%) and exhibits negative AT- and GC-skews. All PCGs are initiated by canonical ATN start codons, except for Cytochrome Oxidase subunit 1 (COI), which is initiated by CGA. Most PCGs have a complete typical stop codon (TAA). Only NAD1 has a TAG stop codon and the COII and NAD5 genes have an incomplete stop codon consisting of just a T. The A+T-rich region is 332 bp long and contains common features found in lepidopteran mitogenomes, including the 'ATAGA' motif, a 17 bp poly (T) stretch and a (AT)8 element preceded by the 'ATTTA' motif. Other tandem repeats like (TAA)4 and (TAT)7 were found, as well as (T)6 and (A)10 mononucleotide repeat elements. Finally, this mitogenome has 20 intergenic spacer regions. The phylogenetic relationship of T. solanivora with 28 other lepidopteran families (12 superfamilies) showed that taxonomic classification by morphological features coincides with the inferred phylogeny. Thus, the Gelechiidae family represents a monophyletic group, suggesting that T. solanivora and Pectinophora gossypiella have a recent common ancestor. PMID- 26802973 TI - Genetic expression analysis of E2F-associated phosphoprotein in stress responses in the mouse. AB - Dysfunction of the monoaminergic system is critical in stress and anxiety disorders, but the role of each family member in the development of stress related psychopathologies is not sufficiently understood. Eapp has been reported to be a transcriptional repressor of monoamine oxidase B (Maob) and down regulates Maob via the Maob core promoter. In the present study, we more specifically examine the role of Eapp in stress responses by testing the hypothesis that Eapp may be involved in the occurrence and development of stress responses. Western blotting, qPCR and immunohistochemistry were used to investigate the expression variation of Eapp in hypothalamus tissue after exposure to stress. The expression of Eapp is controlled by a cis-acting quantitative trait locus (cis-eQTL). Two genes Sphk2 and Nosip, had trans-eQTLs that mapped to the location of Eapp and altered expression of these two genes was shown following siRNA knockdown of Eapp. Additionally, Mmp9, Npy, Npy5r and Maob were shown to have different expression levels in the Eapp knock-down experiments. Our data provide strong evidence that the cis-modulated gene, Eapp, is associated with stress responses, and that validated downstream targets and members of Eapp gene network may also be involved in the development of stress. PMID- 26802974 TI - Different visuomotor processes maturation rates in children support dual visuomotor learning systems. AB - Different processes are involved during visuomotor learning, including an error based procedural and a strategy based cognitive mechanism. Our objective was to analyze if the changes in the adaptation or the aftereffect components of visuomotor learning measured across development, reflected different maturation rates of the aforementioned mechanisms. Ninety-five healthy children aged 4 12years and a group of young adults participated in a wedge prism and a dove prism throwing task, which laterally displace or horizontally reverse the visual field respectively. The results show that despite the age-related differences in motor control, all children groups adapted in the error-based wedge prisms condition. However, when removing the prism, small children showed a slower aftereffects extinction rate. On the strategy-based visual reversing task only the older children group reached adult-like levels. These results are consistent with the idea of different mechanisms with asynchronous maturation rates participating during visuomotor learning. PMID- 26802975 TI - Different coordination and flexibility of the spine and pelvis during lateral bending between young and older adults. AB - This study examined coordination of the spine and pelvis during lateral bending of the trunk in older adults. Thirty-four healthy subjects (17 young and 17 older adults) demonstrated lateral bending at a controlled speed while holding a bar at approximately 180 degrees of shoulder flexion. Kinematic data collection was completed on the thoracic spine, lumbar spine, and pelvis. The coupling angle was calculated to examine the thorax-lumbar, lumbar-pelvis, and thorax-pelvis coordination patterns. The older adults demonstrated a reduced range of motion (ROM) of the lumbar spine, while both groups revealed similar ROM in the thorax and in the pelvis. The coupling angle between the straightening and bending phases was different only for the older adults in the thorax-lumbar (23.4+/-8.0 vs. -1.6+/-4.4, p=0.004) and the lumbar-pelvis (65.4+/-7.2 vs. 86.1+/-7.8, p=0.001) coordination. However, there was no group difference in the thorax pelvis coordination. These findings indicate that age-related changes in the lumbar region affect coordination patterns only during the bending phase. The older adults preserved a similar pattern of movement to the young adults during the straightening phase, but the coordination variability of the coupling angles was greater for the older adults than for the young adults. This movement pattern suggests that the older adults lacked consistent trunk control in an attempt to optimize lateral bending coordination. PMID- 26802976 TI - Estimation of post mortem interval by tomographic images of intra-cardiac hypostasis. AB - The determination of the post mortem interval (PMI) is important in many instances, especially in criminal investigations. So, we consider post mortem tomographic evaluation of intra-cardiac hypostasis as an additional method for such purpose. Tomographic images of the thoraces of the corpses of 23 patients who died in a hospital were obtained sequentially at one hour intervals to allow the analysis of changes in density due to hypostasis over time. The right and left atria, which appear in the mediastinal window, were selected for measurements of the average organ density. An exponential model was used to relate the difference between the attenuation coefficients of the anterior segment of the right atrium and the posterior segment of the left atrium to the PMI. In spite of the large variability of the data from this observational study, PMI estimates during the first 12 h after death can be estimated with a margin of error smaller than two hours. The results suggest that the difference between the attenuation coefficients stabilizes around 12 h post mortem and may be used as an additional method to estimate the PMI. PMID- 26802977 TI - Engineering synthetic bacterial consortia for enhanced desulfurization and revalorization of oil sulfur compounds. AB - The 4S pathway is the most studied bioprocess for the removal of the recalcitrant sulfur of aromatic heterocycles present in fuels. It consists of three sequential functional units, encoded by the dszABCD genes, through which the model compound dibenzothiophene (DBT) is transformed into the sulfur-free 2-hydroxybiphenyl (2HBP) molecule. In this work, a set of synthetic dsz cassettes were implanted in Pseudomonas putida KT2440, a model bacterial "chassis" for metabolic engineering studies. The complete dszB1A1C1-D1 cassette behaved as an attractive alternative to the previously constructed recombinant dsz cassettes - for the conversion of DBT into 2HBP. Refactoring the 4S pathway by the use of synthetic dsz modules encoding individual 4S pathway reactions revealed unanticipated traits, e.g., the 4S intermediate 2HBP-sulfinate (HBPS) behaves as an inhibitor of the Dsz monooxygenases, and once secreted from the cells it cannot be further taken up. That issue should be addressed for the rational design of more efficient biocatalysts for DBT bioconversions. In this sense, the construction of synthetic bacterial consortia to compartmentalize the 4S pathway into different cell factories for individual optimization was shown to enhance the conversion of DBT into 2HBP, overcome the inhibition of the Dsz enzymes by the 4S intermediates, and enable efficient production of unattainable high added value intermediates, e.g., HBPS, that are difficult to obtain using the current monocultures. PMID- 26802979 TI - Initial severity and efficacy of risperidone in autism: Results from the RUPP trial. AB - BACKGROUND: Risperidone is a common psychopharmacological treatment for irritability in autism spectrum disorder (ASD). It is not well-established how effective risperidone is across the initial symptom severity range. This study aims to examine the influence of baseline severity on the efficacy of risperidone in the treatment of ASD. METHODS: Participants were from the NIMH funded RUPP multisite, randomized, double-blind trial that compared risperidone to placebo to treat autistic disorder with severe tantrums, aggression, or self-injury. Participants were aged 5 to 17, and randomly assigned to risperidone (n=49) or placebo (n=52). Baseline and change scores were computed with the Aberrant Behavior Checklist (ABC) parent assessed scales with irritability as the primary outcome, as well as the clinician assessed ABC Irritability subscale, and Clinical Global Impression Scale. RESULTS: The relationship between baseline severity and change scores for the risperdone and placebo groups was examined with eight competing three-level mixed-effects models for repeated measure models. Significant (P<0.01) interactions between treatment and baseline severity were observed for parent ABC ratings of irritability and lethargy only. Greater magnitudes of the differences between risperidone and placebo were observed from moderate to very severe baseline severity on irritability and lethargy. Initial severity values over approximately 30 had a strong effect on symptom change [irritability: effect size (ES)=1.9, number needed to treat (NNT)=2, lethargy ES=0.9, NNT=5]. CONCLUSIONS: Parents may expect benefits of risperidone on irritability and lethargy with moderate to severe symptoms of ASD. TRIAL REGISTRATION: Registry name: ClinicalTrials.gov, trial identifier: NCT00005014, URL: http://www.clinicaltrials.gov/ct2/show/NCT00005014?term=NCT00005014&rank=1, registered on March 31, 2000. PMID- 26802978 TI - Increased ventricular cerebrospinal fluid lactate in depressed adolescents. AB - BACKGROUND: Mitochondrial dysfunction has been increasingly examined as a potential pathogenic event in psychiatric disorders, although its role early in the course of major depressive disorder (MDD) is unclear. Therefore, the purpose of this study was to investigate mitochondrial dysfunction in medication-free adolescents with MDD through in vivo measurements of neurometabolites using high spatial resolution multislice/multivoxel proton magnetic resonance spectroscopy. METHODS: Twenty-three adolescents with MDD and 29 healthy controls, ages 12-20, were scanned at 3T and concentrations of ventricular cerebrospinal fluid lactate, as well as N-acetyl-aspartate (NAA), total creatine (tCr), and total choline (tCho) in the bilateral caudate, putamen, and thalamus were reported. RESULTS: Adolescents with MDD exhibited increased ventricular lactate compared to healthy controls [F(1,41)=6.98, P=0.01]. However, there were no group differences in the other neurometabolites. Dimensional analyses in the depressed group showed no relation between any of the neurometabolites and symptomatology, including anhedonia and fatigue. CONCLUSIONS: Increased ventricular lactate in depressed adolescents suggests mitochondrial dysfunction may be present early in the course of MDD; however it is still not known whether the presence of mitochondrial dysfunction is a trait vulnerability of individuals predisposed to psychopathology or a state feature of the disorder. Therefore, there is a need for larger multimodal studies to clarify these chemical findings in the context of network function. PMID- 26802980 TI - An online intervention using information on the mental health-mental illness continuum to reduce stigma. AB - BACKGROUND: A core component of stigma is being set apart as a distinct, dichotomously different kind of person. We examine whether information on a continuum from mental health to mental illness reduces stigma. METHOD: Online survey experiment in a quota sample matching the German population for age, gender and region (n=1679). Participants randomly received information on either (1) a continuum, (2) a strict dichotomy of mental health and mental illness, or (3) no information. We elicited continuity beliefs and stigma toward a person with schizophrenia or depression. RESULTS: The continuum intervention decreased perceived difference by 0.19 standard deviations (SD, P<0.001) and increased social acceptance by 0.18 SD (P=0.003) compared to the no-text condition. These effects were partially mediated by continuity beliefs (proportion mediated, 25% and 26%), which increased by 0.19 SD (P<0.001). The dichotomy intervention, in turn, decreased continuity beliefs and increased notions of difference, but did not affect social acceptance. CONCLUSION: Attitudes towards a person with mental illness can be improved by providing information on a mental health-mental illness continuum. PMID- 26802981 TI - Epidemiology and socioeconomic impact of seasonal affective disorder in Austria. AB - BACKGROUND: Seasonal affective disorder (SAD) is a subtype of recurrent depressive or bipolar disorder that is characterized by regular onset and remission of affective episodes at the same time of the year. The aim of the present study was to provide epidemiological data and data on the socioeconomic impact of SAD in the general population of Austria. METHODS: We conducted a computer-assisted telephone interview in 910 randomly selected subjects (577 females and 333 males) using the Seasonal Health Questionnaire (SHQ), the Seasonal Pattern Assessment Questionnaire (SPAQ), and the Sheehan Disability Scale (SDS). Telephone numbers were randomly drawn from all Austrian telephone books and transformed using the random last digits method. The last birthday method was employed to choose the target person for the interviews. RESULTS: Out of our subjects, 2.5% fulfilled criteria for the seasonal pattern specifier according to DSM-5 and 2.4% (95% CI=1.4-3.5%) were diagnosed with SAD. When applying the ICD-10 criteria 1.9% (95% CI=0.9-2.8%) fulfilled SAD diagnostic criteria. The prevalence of fall-winter depression according to the Kasper Rosenthal criteria was determined to be 3.5%. The criteria was fulfilled by 15.1% for subsyndromal SAD (s-SAD). We did not find any statistically significant gender differences in prevalence rates. When using the DSM-5 as a gold standard for the diagnosis of SAD, diagnosis derived from the SPAQ yielded a sensitivity of 31.8% and a specificity of 97.2%. Subjects with SAD had significantly higher scores on the SDS and higher rates of sick leave and days with reduced productivity than healthy subjects. CONCLUSIONS: Prevalence estimates for SAD with the SHQ are lower than with the SPAQ. Our data are indicative of the substantial burden of disease and the socioeconomic impact of SAD. This epidemiological data shows a lack of gender differences in SAD prevalence. The higher rates of females in clinical SAD samples might, at least in part, be explained by lower help seeking behaviour in males. PMID- 26802982 TI - Burnout syndrome among psychiatric trainees in 22 countries: Risk increased by long working hours, lack of supervision, and psychiatry not being first career choice. AB - BACKGROUND: Postgraduate medical trainees experience high rates of burnout, but evidence regarding psychiatric trainees is missing. We aim to determine burnout rates among psychiatric trainees, and identify individual, educational and work related factors associated with severe burnout. METHODS: In an online survey psychiatric trainees from 22 countries were asked to complete the Maslach Burnout Inventory (MBI-GS) and provide information on individual, educational and work related parameters. Linear mixed models were used to predict the MBI-GS scores, and a generalized linear mixed model to predict severe burnout. RESULTS: This is the largest study on burnout and training conditions among psychiatric trainees to date. Complete data were obtained from 1980 out of 7625 approached trainees (26%; range 17.8-65.6%). Participants were 31.9 (SD 5.3) years old with 2.8 (SD 1.9) years of training. Severe burnout was found in 726 (36.7%) trainees. The risk was higher for trainees who were younger (P<0.001), without children (P=0.010), and had not opted for psychiatry as a first career choice (P=0.043). After adjustment for socio-demographic characteristics, years in training and country differences in burnout, severe burnout remained associated with long working hours (P<0.001), lack of supervision (P<0.001), and not having regular time to rest (P=0.001). Main findings were replicated in a sensitivity analysis with countries with response rate above 50%. CONCLUSIONS: Besides previously described risk factors such as working hours and younger age, this is the first evidence of negative influence of lack of supervision and not opting for psychiatry as a first career choice on trainees' burnout. PMID- 26802983 TI - Cosegregation of serum cholesterol with cholesterol intestinal absorption markers in families with primary hypercholesterolemia without mutations in LDLR, APOB, PCSK9 and APOE genes. AB - BACKGROUND AND AIM: The genetic cause and pathogenic mechanism of approximately 20-40% of autosomal dominant hypercholesterolemias (ADH) are unknown. Increased cholesterol intestinal absorption has been associated to ADH. If this variation contributes to their pathogenesis is unknown. METHODS AND RESULTS: We studied cholesterol absorption (phytosterols and cholestanol serum concentrations) and cholesterol synthesis (desmosterol serum concentration) in 20 families with ADH without causal mutations in LDLR, APOB, PCSK9 or APOE genes (non-FH ADH) selected from 54 non-FH ADH probands with (non-cholesterol sterol concentrations above 75th percentile) and without (under 75th percentile) hyperabsorption. The concentrations of cholestanol, sitosterol, campesterol and stigmasterol were higher in affected than in non-affected subjects (p = 0.003, <0.001.<0.001, 0.002, respectively). There was a strong cosegregation of hyperabsorption with high LDL cholesterol within hyperabsorber families with odds ratio 6.80 (confidence interval 1.656-27.9), p = 0.008. In hyperabsorber families, 60.5% of subjects were hyperabsorbers and 76% of them had high LDL cholesterol versus 38.3% and 63% in non-hyperabsorber families, respectively. CONCLUSION: Most hypercholesterolemic family members with a hyperabsorber proband are hyperabsorbers. These absorption markers are significantly and positively associated with LDL cholesterol, and predispose to high LDL cholesterol in family members. Our data suggest that complex interindividual variation in cholesterol absorption is involved in many non-FH ADH. PMID- 26802984 TI - Telelap ALF-X total hysterectomy for early stage endometrial cancer: New frontier of robotic gynecological surgery. PMID- 26802985 TI - Chronic peripheral inflammation, hippocampal neurogenesis, and behavior. AB - Adult hippocampal neurogenesis is involved in memory and learning, and disrupted neurogenesis is implicated in cognitive impairment and mood disorders, including anxiety and depression. Some long-term peripheral illnesses and metabolic disorders, as well as normal aging, create a state of chronic peripheral inflammation. These conditions are associated with behavioral disturbances linked to disrupted adult hippocampal neurogenesis, such as cognitive impairment, deficits in learning and memory, and depression and anxiety. Pro-inflammatory cytokines released in the periphery are involved in peripheral immune system-to brain communication by activating resident microglia in the brain. Activated microglia reduce neurogenesis by suppressing neuronal stem cell proliferation, increasing apoptosis of neuronal progenitor cells, and decreasing survival of newly developing neurons and their integration into existing neuronal circuits. In this review, we summarize evolving evidence that the state of chronic peripheral inflammation reduces adult hippocampal neurogenesis, which, in turn, produces the behavioral disturbances observed in chronic inflammatory disorders. As there are no data available on neurogenesis in humans with chronic peripheral inflammatory disease, we focus on animal models and, in parallel, consider the evidence of cognitive disturbance and mood disorders in human patients. PMID- 26802987 TI - Unlocking the Potential of the Patient Portal for Adolescent Health. PMID- 26802986 TI - MHCI promotes developmental synapse elimination and aging-related synapse loss at the vertebrate neuromuscular junction. AB - Synapse elimination at the developing neuromuscular junction (NMJ) sculpts motor circuits, and synapse loss at the aging NMJ drives motor impairments that are a major cause of loss of independence in the elderly. Here we provide evidence that at the NMJ, both developmental synapse elimination and aging-related synapse loss are promoted by specific immune proteins, members of the major histocompatibility complex class I (MHCI). MHCI is expressed at the developing NMJ, and three different methods of reducing MHCI function all disrupt synapse elimination during the second postnatal week, leaving some muscle fibers multiply-innervated, despite otherwise outwardly normal synapse formation and maturation. Conversely, overexpressing MHCI modestly accelerates developmental synapse elimination. MHCI levels at the NMJ rise with aging, and reducing MHCI levels ameliorates muscle denervation in aged mice. These findings identify an unexpected role for MHCI in the elimination of neuromuscular synapses during development, and indicate that reducing MHCI levels can preserve youthful innervation of aging muscle. PMID- 26802988 TI - Meaningful Use of a Confidential Adolescent Patient Portal. AB - PURPOSE: To design and evaluate the usage of an adolescent patient portal specifically adapted for adolescent health care needs that also satisfied institutional meaningful use guidelines regarding electronic health records. METHODS: Key stakeholders at one academic health care center adopted an online portal and opted to designate a patient portal specifically for adolescents to maximize confidentiality in compliance with state privacy laws. This study analyzed aggregate electronic health record data of adolescents' (ages 12-17.9 years) uptake, usage, and functionality of this portal and compared it to parent portal usage for younger children (ages 0-11 years). Differences in means were calculated using paired t tests. RESULTS: The portal was used similarly between parents of young children and adolescents, with almost 1,000 enrollees in each group from September 1, 2012 to March 31, 2015. There were no gender differences in enrollment. Adolescents were less likely than parents of younger children to review appointments (73% vs. 85%), laboratory tests (67% vs. 79%), problem lists (40% vs. 78%), or allergies (45% vs. 77%, all p values <.001). Parents of younger children more frequently messaged providers (3,297 messages) although adolescents sent 1,397 confidential messages. CONCLUSIONS: Institutional decisions for implementing meaningful use requirements can align with goals of adolescent health. Patient portals can enhance adolescent health care quality and adolescents readily use a confidential portal. Implementation of meaningful use requirements should be checked against adolescent health care needs to maximize confidentiality and promote health communication. PMID- 26802989 TI - Characterizing Key Components of a Medical Home Among Rural Adolescents. AB - PURPOSE: Adolescents in rural areas have higher unmet medical needs and receive fewer preventive health care visits than their urban counterparts. This community health assessment aimed to describe adolescent experiences of key components of a medical home in rural Washington. METHODS: A cross-sectional survey using questions from two validated measures was created with input from a community advisory group using community-based participatory research principles. The survey was administered to a convenience sample of high-school students in one rural town. Responses within each medical home domain were grouped to create composite scores. Linear and logistic regression analyses identified characteristics associated with receiving medical home services. RESULTS: A total of 217 adolescents aged 13-19 years completed the survey. Eighty-five percent identified as Latino/Hispanic. Respondents described usually or always feeling listened to by providers (80%), respected by providers (89%), and welcomed at their clinic (79%). Fewer reported having a personal health provider (56%), meeting alone with a provider (56%), or knowing the visit was confidential (60%). Those who identified having a primary provider had 2.48 greater odds (95% confidence interval = 1.13-5.45) of reporting a well visit in the previous year and had higher composite scores for compassionate and patient-centered care. CONCLUSIONS: This sample of rural adolescents reported receiving many characteristics of a medical home but had limited experience with personal providers and confidential services. Improving adolescent access to confidential care may be especially important in small, rural communities. The association of a primary provider with improved medical home experience highlights this key characteristic in an adolescent medical home. PMID- 26802990 TI - Factors Associated With Interest in Same-Day Contraception Initiation Among Females in the Pediatric Emergency Department. AB - PURPOSE: The purposes were to describe interest in hormonal contraception initiation among female adolescent in the emergency department (ED) and to assess for associations with factors known to increase pregnancy risk such as violence victimization. METHODS: We used a computerized survey to assess sexual and dating practices, pregnancy history/likelihood, contraception use (including long-acting reversible contraception [LARC]) and concerns, contraception initiation interest, violence victimization, medical utilization, and demographics among sexually experienced females aged 14-19 years in our ED. The primary outcome was interest in contraception initiation. We compared responses between subgroups using the chi-square test. RESULTS: A total of 168 adolescents participated (82% of approached; mean age 16.6 years; 41% white; 48% black; 21% commercial insurance). Interest in contraception initiation was high: 60% overall and 70% among those not using hormonal contraception (n = 96). Among those using non-LARC contraception (n = 59), 29% were interested in LARC initiation. Contraception/LARC interest was positively associated with lack of recent well care (p < .06) and concerns about cost (p < .01), privacy (p = .03), and where to obtain contraception (p < .01). Nearly all planned on avoiding pregnancy, although many (23%) used no contraception at last intercourse. One third (36%) reported violence victimization. Most (70%) reported >=1 concern about contraception (most commonly cost). CONCLUSIONS: Many reported behaviors and exposures, including violence victimization, that increase their risk for pregnancy and most expressed interest in same-day initiation of hormonal contraception, including LARC. These findings may inform novel strategies for increased adolescent access to contraception and pregnancy prevention through use of nontraditional sites such as EDs. PMID- 26802991 TI - The Influence of the Breast on Sport and Exercise Participation in School Girls in the United Kingdom. AB - PURPOSE: Emerging evidence suggests that breasts may be a barrier to physical activity for adult females. With only 12% of the UK 14-year-old girls achieving exercise guidelines, to understand deterrents to exercise in this population, we should consider whether breasts may also influence sport and exercise participation in school girls. This survey-based study investigated the influence of the breast on sport and exercise participation and breast-specific concerns in the UK school girls. METHODS: A survey was developed to assess demographics, breast characteristics, breast-specific concerns in sports, breast knowledge, views on breast education, and sport participation. Chi-squared tests assessed associations between participation and breast size, sports bra use, and breast concerns. RESULTS: Two thousand eighty-nine school girls aged 11-18 years completed the survey, for 97 their breasts had begun developing and 96% reported wearing breast support. Forty-six percent of girls reported that their breasts had some effect on their participation in compulsory sports and exercise, which was more prevalent in girls aged 13-14 years (51%) and in larger-breasted girls (63%). More than 50% reported never wearing a sports bra during sports. Breast concerns were high with 73% reporting >=1 breast-specific concern in sports; with breast bounce being most prevalent (38%). CONCLUSIONS: As most of the breast concerns raised in this survey could be addressed via education and 87% of girls wanted to know more about breasts, this study demonstrates a need for breast education for school girls, which may reduce the influence of the breast on sport and exercise participation. PMID- 26802992 TI - Physician Advice to Adolescents About Smoking: Who Gets Advised and Who Benefits Most? AB - PURPOSE: The Clinical Practice Guidelines instruct physicians to ask their patients about smoking and to advise against tobacco use. Physicians are urged especially to attend to racial minorities and teens because of these groups' increased susceptibility to smoking. Research on race and physician advice against smoking has produced contradictory findings. The purpose of this study is to clarify the relationships between physician communication about tobacco, race, and smoking among adolescents. METHODS: This cross-sectional retrospective study explored (1) racial differences in rates of receiving physician communication and (2) whether the relationship between physician communication and smoking among adolescents was moderated by race. Multiple measures of smoking status were used (e.g., intentions to quit, quit attempts, quits, relapse status). We used a large (N = 5,154), predominately African-American (82.9%) sample of 11th graders. RESULTS: Regular smokers were more likely to be screened about smoking. African Americans were more frequently advised against tobacco than Caucasians. Among African Americans, nonsmokers were most likely to be both screened and advised; among Caucasians, regular were most likely to be screened and advised. Overall, physician intervention was associated with greater benefits for young African Americans, including fewer intentions to smoke, greater likelihood of quitting, and less relapse. CONCLUSIONS: Physician communication about smoking may hold particular promise for African-American teens, reducing health disparities because of racial differences in smoking-related mortality and morbidity. Physicians should be encouraged to screen and advise all young people about tobacco, regardless of race or smoking status. PMID- 26802993 TI - Intimate Partner Violence and Sex Among Young Men Who Have Sex With Men. AB - PURPOSE: Among young men who have sex with men (YMSM) few studies have examined the relationship between intimate partner violence (IPV) perpetration versus victimization and sexual behaviors. METHODS: Using data from n = 528 urban YMSM, multinomial logistic regression models were built to examine the distinct relationships between any IPV, victimization, and perpetration with condomless sex in the previous 30 days, controlling for key sociodemographic characteristics. RESULTS: In this sample of YMSM, lifetime experience of any IPV was associated with increased odds of recent condomless oral (adjusted odds ratio [AOR] = 1.81, 95% confidence interval [CI] = 1.21-2.72) and anal receptive sex (AOR= 2.29, 95% CI = 1.22-4.31). IPV victimization was associated with a greater likelihood of condomless receptive anal sex (AOR= 2.12, 95% CI = 1.15-3.93) whereas IPV perpetration was associated with increased odds of condomless receptive (AOR= 2.11, 95% CI = 1.14-3.91) and insertive (AOR= 2.21, 95% CI = 1.06 4.59) anal sex. CONCLUSIONS: Among YMSM, reports of both IPV perpetration and victimization were associated with increased odds of recent condomless sex. These findings indicate that the need for IPV prevention and intervention programs for this new generation of YMSM is highly warranted. PMID- 26802994 TI - Protective Effects of Adolescent-Adult Connection on Male Youth in Urban Environments. AB - PURPOSE: Positive adult connection has been linked with protective effects among U.S. adolescents. Less is known about the impact of adult connection across multiple health domains for youth in low-resource urban environments. We examined the associations between adult connection and school performance, substance use, and violence exposure among youth in low-resource neighborhoods. METHODS: We recruited a population-based random sample of 283 male adolescents in Philadelphia. Age-adjusted logistic regression tested whether positive adult connection promoted school performance and protected against substance use and violence exposure. RESULTS: Youth with a positive adult connection had significantly higher odds of good school performance (odds ratio [OR], 2.8; p < .05), and lower odds of alcohol use (OR, .4; p < .05), violence involvement (OR, .3-.4; p < .05), and violence witnessing (OR, .3; p < .05). CONCLUSIONS: Promoting adult connection may help safeguard youth in urban contexts. Youth serving professionals should consider assessing adult connection as part of a strengths-based approach to health promotion for youth in low-resource neighborhoods. PMID- 26802995 TI - Economic and Social Impact of Pertussis Among Adolescents in San Diego County. AB - PURPOSE: During recent pertussis epidemics, adolescents have experienced a large burden of disease. We assessed the impact of pertussis among San Diego adolescents and their households. METHODS: Parents of pertussis patients aged 13 17 years were surveyed about health care utilization, missed work and school, and other factors. Costs of medical visits, medication use, and lost wages were estimated. RESULTS: The parents of 53 (of 108 [49%]) eligible 2013 pertussis patients were interviewed; 51 (96%) of these patients previously received tetanus, diphtheria, and acellular pertussis vaccine. Medical visits included primary care (81%), urgent care (11%), and emergency department (9%); all patients received antibiotics. Forty-seven households (89%) received a post exposure prophylaxis recommendation, and five (9%) reported >=1 unpaid parental leave day. Thirty-eight patients (72%) missed >=1 school day (mean = 5.4 days). Societal costs were estimated at $315.15 per household and $236,047.35 in San Diego during 2013-2014. CONCLUSIONS: Even among vaccinated adolescents, pertussis can result in considerable societal costs. PMID- 26802996 TI - Emergency Contraception for Adolescents and Young Adults: Guidance for Health Care Professionals. PMID- 26802997 TI - Capillary isotachophoresis with ESI-MS detection: Methodology for highly sensitive analysis of ibuprofen and diclofenac in waters. AB - The possibilities of reaching higher sensitivity in capillary electrophoretic analyses of complex samples with ESI-MS detection were investigated on the example of analysis of diclofenac and ibuprofen in waters. The applied separation approach is based on application of isotachophoresis that ensures permanent stacking of analytes until they reach the detector. Investigation of the possibilities of MS detector optimization have shown that optimization of fragmentor voltage and working in the SIM mode with collection of data for multiple fragments both increases the method specificity and approx. doubles its sensitivity. Combination with an offline SPE preconcentration step resulted in very high sensitivity of the described methodology with a reached LOD below 2 * 10(-12) M, corresponding to analyte levels of 0.6 ng L(-1) of diclofenac and 0.4 ng L(-1) of ibuprofen. The results demonstrate that CE-MS, particularly when performed in the ITP mode, has the potential to reach sensitivities comparable to HPLC-MS. PMID- 26802998 TI - A review of chemical gradient systems for cell analysis. AB - Microfluidic spatial and temporal gradient generators have played an important role in many biological assays such as in the analysis of wound healing, inflammation, and cancer metastasis. Chemical gradient systems can also be applied to other fields such as drug design, chemical synthesis, chemotaxis, etc. Microfluidic systems are particularly amenable to gradient formation, as the length scales used in chips enable fluid processes that cannot be conducted in bulk scale. In this review we discuss new microfluidic devices for gradient generation and applications of those systems in cell analysis. PMID- 26802999 TI - Automation of static and dynamic non-dispersive liquid phase microextraction. Part 2: Approaches based on impregnated membranes and porous supports. AB - A critical overview on automation of modern liquid phase microextraction (LPME) approaches based on the liquid impregnation of porous sorbents and membranes is presented. It is the continuation of part 1, in which non-dispersive LPME techniques based on the use of the extraction phase (EP) in the form of drop, plug, film, or microflow have been surveyed. Compared to the approaches described in part 1, porous materials provide an improved support for the EP. Simultaneously they allow to enlarge its contact surface and to reduce the risk of loss by incident flow or by components of surrounding matrix. Solvent impregnated membranes or hollow fibres are further ideally suited for analyte extraction with simultaneous or subsequent back-extraction. Their use can therefore improve the procedure robustness and reproducibility as well as it "opens the door" to the new operation modes and fields of application. However, additional work and time are required for membrane replacement and renewed impregnation. Automation of porous support-based and membrane-based approaches plays an important role in the achievement of better reliability, rapidness, and reproducibility compared to manual assays. Automated renewal of the extraction solvent and coupling of sample pretreatment with the detection instrumentation can be named as examples. The different LPME methodologies using impregnated membranes and porous supports for the extraction phase and the different strategies of their automation, and their analytical applications are comprehensively described and discussed in this part. Finally, an outlook on future demands and perspectives of LPME techniques from both parts as a promising area in the field of sample pretreatment is given. PMID- 26803000 TI - Sampling frequency, response times and embedded signal filtration in fast, high efficiency liquid chromatography: A tutorial. AB - With increasingly efficient columns, eluite peaks are increasingly narrower. To take full advantage of this, choice of the detector response time and the data acquisition rate a.k.a. detector sampling frequency, have become increasingly important. In this work, we revisit the concept of data sampling from the theorem variously attributed to Whittaker, Nyquist, Kotelnikov, and Shannon. Focusing on time scales relevant to the current practice of high performance liquid chromatography (HPLC) and optical absorbance detection (the most commonly used method), even for very narrow simulated peaks Fourier transformation shows that theoretical minimum sampling frequency is still relatively low (<10 Hz). However, this consideration alone may not be adequate for real chromatograms when an appreciable amount of noise is present. Further, depending on the instrument, the manufacturer's choice of a particular data bunching/integration/response time condition may be integrally coupled to the sampling frequency. In any case, the exact nature of signal filtration often occurs in a manner neither transparent to nor controllable by the user. Using fast chromatography on a state-of-the-art column (38,000 plates), we evaluate the responses produced by different present generation instruments, each with their unique black box digital filters. We show that the common wisdom of sampling 20 points per peak can be inadequate for high efficiency columns and that the sampling frequency and response choices do affect the peak shape. If the sampling frequency is too low or response time is too large, the observed peak shapes will not remain as narrow as they really are - this is especially true for high efficiency and high speed separations. It is shown that both sampling frequency and digital filtering affect the retention time, noise amplitude, peak shape and width in a complex fashion. We show how a square-wave driven light emitting diode source can reveal the nature of the embedded filter. We discuss time uncertainties related to the choice of sampling frequency. Finally, we suggest steps to obtain optimum results from a given system. PMID- 26803001 TI - Total phenol analysis of weakly supported water using a laccase-based microband biosensor. AB - The monitoring of phenolic compounds in wastewaters in a simple manner is of great importance for environmental control. Here, a novel screen printed laccase based microband array for in situ, total phenol estimation in wastewaters and for water quality monitoring without additional sample pre-treatment is presented. Numerical simulations using the finite element method were utilized for the characterization of micro-scale graphite electrodes. Anodization followed by covalent modification was used for the electrode functionalization with laccase. The functionalization efficiency and the electrochemical performance in direct and catechol-mediated oxygen reduction were studied at the microband laccase electrodes and compared with macro-scale electrode structures. The reduction of the dimensions of the enzyme biosensor, when used under optimized conditions, led to a significant improvement in its analytical characteristics. The elaborated microsensor showed fast responses towards catechol additions to tap water - a weakly supported medium - characterized by a linear range from 0.2 to 10 MUM, a sensitivity of 1.35 +/- 0.4 A M(-1) cm(-2) and a dynamic range up to 43 MUM. This enhanced laccase-based microsensor was used for water quality monitoring and its performance for total phenol analysis of wastewater samples from different stages of the cleaning process was compared to a standard method. PMID- 26803002 TI - A fully automated effervescence-assisted switchable solvent-based liquid phase microextraction procedure: Liquid chromatographic determination of ofloxacin in human urine samples. AB - A novel fully automated effervescence-assisted switchable solvent-based liquid phase microextraction procedure has been suggested. In this extraction method, medium-chain saturated fatty acids were investigated as switchable hydrophilicity solvents. The conversion of fatty acid into hydrophilic form was carried out in the presence of sodium carbonate. The injection of sulfuric acid into the solution decreased the pH value of the solution, thus, microdroplets of the fatty acid were generated. Carbon dioxide bubbles were generated in-situ, and promoted the extraction process and final phase separation. The performance of the suggested approach was demonstrated by the determination of ofloxacin in human urine samples using high-performance liquid chromatography with fluorescence detection. This analytical task was used as a proof-of-concept example. Under the optimal conditions, the detector response of ofloxacin was linear in the concentration ranges of 3.10(-8)-3.10(-6) mol L(-1). The limit of detection, calculated from a blank test based on 3sigma, was 1.10(-8) mol L(-1). The results demonstrated that the presented approach is highly cost-effective, simple, rapid and environmentally friendly. PMID- 26803003 TI - Stepped MS(All) Relied Transition (SMART): An approach to rapidly determine optimal multiple reaction monitoring mass spectrometry parameters for small molecules. AB - Multiple reaction monitoring (MRM) is a universal approach for quantitative analysis because of its high specificity and sensitivity. Nevertheless, optimization of MRM parameters remains as a time and labor-intensive task particularly in multiplexed quantitative analysis of small molecules in complex mixtures. In this study, we have developed an approach named Stepped MS(All) Relied Transition (SMART) to predict the optimal MRM parameters of small molecules. SMART requires firstly a rapid and high-throughput analysis of samples using a Stepped MS(All) technique (sMS(All)) on a Q-TOF, which consists of serial MS(All) events acquired from low CE to gradually stepped-up CE values in a cycle. The optimal CE values can then be determined by comparing the extracted ion chromatograms for the ion pairs of interest among serial scans. The SMART predicted parameters were found to agree well with the parameters optimized on a triple quadrupole from the same vendor using a mixture of standards. The parameters optimized on a triple quadrupole from a different vendor was also employed for comparison, and found to be linearly correlated with the SMART predicted parameters, suggesting the potential applications of the SMART approach among different instrumental platforms. This approach was further validated by applying to simultaneous quantification of 31 herbal components in the plasma of rats treated with a herbal prescription. Because the sMS(All) acquisition can be accomplished in a single run for multiple components independent of standards, the SMART approach are expected to find its wide application in the multiplexed quantitative analysis of complex mixtures. PMID- 26803004 TI - Facile synthesis of hydrophilic polyamidoxime polymers as a novel solid-phase extraction matrix for sequential characterization of glyco- and phosphoproteomes. AB - Selective enrichment of glycopeptides or phosphopeptides with great biological significance is essential for high-throughput mass spectrometry analysis. However, most previously reported methods only focused on enriching either glycopeptides or phosphopeptides rather than enriching them both. In this work, for the first time, a facile route was developed for the synthesis of polyamidoxime polymers with intrinsic hydrophilic skeletons and attractive long chain structure. The polyamidoxime materials (co-PAN) were synthesized from polyacrylonitrile (PAN) precursor and were successfully used for selective enrichment of glycopeptides. After that, co-PAN as a matrix functionalized with titanium ions (co-PAN@Ti(4+)) could efficiently enrich phosphopeptides. The performances of the polymers for sequential selective and effective enrichment of glycopeptides and phosphopeptides were evaluated with standard peptide mixtures and human serum. Moreover, the efficiency of enrichment of the material was still retained after being used repeatedly. These results demonstrated that the polymers showed great potential in the practical application of proteomics. PMID- 26803005 TI - Effects of thermal treatments on microstructure and mechanical properties of a Co Cr-Mo-W biomedical alloy produced by laser sintering. AB - Direct Metal Laser Sintering (DMLS) technology based on a layer by layer production process was used to produce a Co-Cr-Mo-W alloy specifically developed for biomedical applications. The alloy mechanical response and microstructure were investigated in the as-sintered state and after post-production thermal treatments. Roughness and hardness measurements, and tensile and flexural tests were performed to study the mechanical response of the alloy while X-ray diffraction (XRD), electron microscopy (SEM, TEM, STEM) techniques and microanalysis (EDX) were used to investigate the microstructure in different conditions. Results showed an intricate network of epsilon-Co (hcp) lamellae in the gamma-Co (fcc) matrix responsible of the high UTS and hardness values in the as-sintered state. Thermal treatments increase volume fraction of the epsilon-Co (hcp) martensite but slightly modify the average size of the lamellar structure. Nevertheless, thermal treatments are capable of producing a sensible increase in UTS and hardness and a strong reduction in ductility. These latter effects were mainly attributed to the massive precipitation of an hcp Co3(Mo,W)2Si phase and the contemporary formation of Si-rich inclusions. PMID- 26803006 TI - Inter-caste communication in social insects. AB - Social insect colonies function as highly integrated units despite consisting of many individuals. This requires the different functional parts of the colony (e.g. different castes) to exchange information that aid in colony functioning and ontogeny. Here we discuss inter-caste communication in three contexts, firstly, the communication between males and females during courtship, secondly, the communication between queens and workers that regulate reproduction and thirdly, the communication between worker castes that allows colonies to balance the number of different worker types. Some signals show surprising complexity in both their chemistry and function, whereas others are simple compounds that were probably already used as pheromones in the solitary ancestors of several social insect lineages. PMID- 26803007 TI - Functionalized magnetic nanochains with enhanced MR imaging: A novel nanosystem for targeting and inhibition of early glioma. AB - Absence of efficient targeting limits the application of magnetic nanochains (NCs) in the diagnosis of early brain cancer. Herein, dextran-coated NCs (more than 100 nm length and ~ 10 nm cores diameter), which were modified by cyclic pentapeptide c(RGDyC) or chlorotoxin (CTX) as the targeting molecules, were fabricated via carbodiimide chemistry and thiol technique. The analysis results revealed that the obtained slender NCs exhibited good biocompatibility, superparamagnetic property, high transverse relaxivity (R2) and longer blood circulation time. The test results of human umbilical vein endothelial cells and U251 human glioma cells indicated that the conjugation of c(RGDyC) could obviously increase the cyto-internalization of c(RGDyC)-NCs, however, CTX modification could significantly enhance accumulation of CTX-NCs in U251 cells, leading to cellular apoptosis. The results of in vivo biodistribution tests and in vivo magnetic resonance (MR) imaging indicated that, although the c(RGDyC)-NCs could target early glioma to some extent and obviously enhance the contrast of MR imaging, CTX-NCs possessed higher tumor-targeting ability and good inhibition effect than the c(RGDyC)-NCs, suggesting that CTX-NCs are promising candidates for the diagnosis and therapy of early glioma. PMID- 26803008 TI - Biodiesel production using lipase immobilized on epoxychloropropane-modified Fe3O4 sub-microspheres. AB - Superparamagnetic Fe3O4 sub-microspheres with diameters of approximately 200 nm were prepared via a solvothermal method, and then modified with epoxychloropropane. Lipase was immobilized on the modified sub-microspheres. The immobilized lipase was used in the production of biodiesel fatty acid methyl esters (FAMEs) from acidified waste cooking oil (AWCO). The effects of the reaction conditions on the biodiesel yield were investigated using a combination of response surface methodology and three-level/three-factor Box-Behnken design (BBD). The optimum synthetic conditions, which were identified using Ridge max analysis, were as follows: immobilized lipase:AWCO mass ratio 0.02:1, fatty acid:methanol molar ratio 1:1.10, hexane:AWCO ratio 1.33:1 (mL/g), and temperature 40 degrees C. A 97.11% yield was obtained under these conditions. The BBD and experimental data showed that the immobilized lipase could generate biodiesel over a wide temperature range, from 0 to 40 degrees C. Consistently high FAME yields, in excess of 80%, were obtained when the immobilized lipase was reused in six replicate trials at 10 and 20 degrees C. PMID- 26803010 TI - Diversions and Divergence. PMID- 26803009 TI - Unusual flavoenzyme catalysis in marine bacteria. AB - Ever since the discovery of the flavin cofactor more than 80 years ago, flavin dependent enzymes have emerged as ubiquitous and versatile redox catalysts in primary metabolism. Yet, the recent advances in the discovery and characterization of secondary metabolic pathways exposed new roles for flavin mediated catalysis in the generation of structurally complex natural products. Here, we review a selection of key biosynthetic flavoenzymes from marine bacterial secondary metabolism and illustrate how their functional and mechanistic investigation expanded our view of the cofactor's chemical repertoire and led to the discovery of a previously unknown flavin redox state. PMID- 26803011 TI - Variable Clinical Presentations of ABO Incompatibility in Dizygotic Twins. AB - Newborns with ABO blood group incompatibility can have a spectrum of clinical presentations from remaining asymptomatic to severe hemolytic anemia with jaundice. This case presentation discusses dizygotic twins who demonstrated both ends of the clinical spectrum. Similar cases in which there is such extreme variation between twins were not attainable in the current literature, which prompted the authors to present it as a rare occurrence and one that was unexpected based on their past experience with ABO incompatibility both in singletons and in twins. PMID- 26803012 TI - Intraprofessional Excellence in Nursing: Collaborative Strategies for Neonatal Abstinence Syndrome. AB - Neonatal abstinence syndrome (NAS) is a growing public health concern, one that costs the health care system $190-$720 million each year. Recently, state-level perinatal quality collaborative groups have disseminated NAS action plans: customizable frameworks aimed to assist health care systems in identifying, evaluating, treating, and coordinating discharge services for neonates with NAS. Hospital-based neonatal nursing quality improvement teams, including neonatal nurse practitioners (NNPs), neonatal clinical nurse specialists (CNSs), and clinical neonatal nurses, by virtue of their collective academic, administrative, and practical years of experience, are ideally positioned to develop, implement, and evaluate NAS care bundles. The article's purpose is to discuss key elements of an NAS care bundle using the framework of the Perinatal Quality Collaborative of North Carolina NAS action plan as an exemplar. Discussion of evidence-based and nursing-driven metrics will be followed by a discussion of the emerging concept of an inpatient-to-outpatient transitional care NAS management model. PMID- 26803014 TI - Initial Development of C.A.T.E.S.: A Simulation-Based Competency Assessment Instrument for Neonatal Nurse Practitioners. AB - PURPOSE: Determine content validity of global statements and operational definitions and choose scenarios for Competency, Assessment, Technology, Education, and Simulation (C.A.T.E.S.), instrument in development to evaluate multidimensional competency of neonatal nurse practitioners (NNPs). DESIGN: Real time Delphi (RTD) method to pursue four specific aims (SAs): (1) identify which cognitive, technical, or behavioral dimension of NNP competency accurately reflects each global statement; (2) map the global statements to the National Association of Neonatal Nurse Practitioners (NANNP) core competency domains; (3) define operational definitions for the novice to expert performance subscales; and (4) determine the essential scenarios to assess NNPs. SAMPLE: Twenty-five NNPs and nurses with competency and simulation experience Main outcome variable: One hundred percent of global statements correct for competency dimension and all but two correct for NANNP domain. One hundred percent novice to expert operational definitions and eight scenarios chosen. RESULTS: Content validity determined for global statements and novice to expert definitions and essential scenarios chosen. PMID- 26803015 TI - Maternal and Paternal Knowledge and Perceptions Regarding Infant Pain in the NICU. AB - PURPOSE: To investigate parents' knowledge, self-efficacy, and satisfaction about infant pain in the NICU. DESIGN AND SAMPLE: A survey was conducted, and 80 parents (57 mothers and 23 fathers) participated in the study. MAIN OUTCOME VARIABLE: A researcher-developed questionnaire composed of 3 dimensions: parents' knowledge about infant pain, perception of self-efficacy regarding infant pain, and satisfaction with infant pain management. RESULTS: Most parents had adequate knowledge and moderate to high self-efficacy and were satisfied with infant pain management in the NICU. Mothers and fathers responded differently regarding self efficacy and satisfaction, and parents' perceptions were correlated with infants' correct age and parents' own age. Most important, most parents wanted to be present and to be given the opportunity to comfort their infant during and after a painful procedure. Parents also preferred to receive formal/written information on infant pain. PMID- 26803016 TI - High-Fidelity Simulation for Neonatal Nursing Education: An Integrative Review of the Literature. AB - The lack of safe avenues to develop neonatal nursing competencies using human subjects leads to the notion that simulation education for neonatal nurses might be an ideal form of education. This integrative literature review compares traditional, teacher-centered education with high-fidelity simulation education for neonatal nurses. It examines the theoretical frameworks used in neonatal nursing education and outlines the advantages of this type of training, including improving communication and teamwork; providing an innovative pedagogical approach; and aiding in skill acquisition, confidence, and participant satisfaction. The importance of debriefing is also examined. High-fidelity simulation is not without disadvantages, including its significant cost, the time associated with training, the need for very complex technical equipment, and increased faculty resource requirements. Innovative uses of high-fidelity simulation in neonatal nursing education are suggested. High-fidelity simulation has great potential but requires additional research to fully prove its efficacy. PMID- 26803017 TI - Brain Natriuretic Peptide: It's Not About the Brain or Just Another Smart Polypeptide--It's About the Heart. AB - Brain natriuretic peptide (BNP) is a cardiac hormone with diuretic, natriuretic, and vasodilator properties. Measurement of plasma B-type natriuretic peptide concentrations is increasingly used to aid diagnosis, assess prognosis, and tailor treatment in adults with congestive heart failure. Recent studies suggest that the peptide is also useful in pediatric patients. The diagnostic role of plasma BNP in neonates admitted to the NICU has shown promise as an aid in diagnosis in neonates with signs of congenital heart disease; as a biomarker of bronchopulmonary dysplasia, patent ductus arteriosus, and persistent pulmonary hypertension of the newborn; a predictive biomarker of the response to indomethacin in preterm infants; and, more significantly, in acute heart failure. PMID- 26803019 TI - News of the Academy of Neonatal Nursing. PMID- 26803020 TI - Editorial: Algae-based Technologies for Sustainable Management of Water Resource Recovery Facilities. PMID- 26803021 TI - Solids Retention Time Dependent Phototrophic Growth and Population Changes in Chemostat Cultivation Using Wastewater. AB - There has been renewed interest in using algae for wastewater polishing and treatment in recent years. Because solids retention time (SRT) is a key design and operating parameter in bioreactor operation, this research determined the effect of SRT on phototrophic growth and microbial population dynamics in continuous-flow chemostat systems. There was a unique feature of phototrophic growth that differed from chemotrophic growth in chemostat. It was found that the phototrophic biomass concentration increased proportionally as SRT increased from 3 to 9 days. Regardless of the change in SRT, a step function model was successfully applied with the predicted phototrophic production rate of 4.5 +/- 0.9 g/m(2).d at the light intensity of 68.5 MUmol/m(2).s. Even though the continuous-flow systems were initially seeded with a 1:1 mixture of green algae and cyanobacteria, Chlorella vulgaris always dominated (98%) in the continuous flow chemostat systems under steady-state conditions. PMID- 26803022 TI - Anaerobic Co-Digestion of Microalgae Scenedesmus sp. and TWAS for Biomethane Production. AB - The paper investigated the feasibility of biomethane (bio-CH4) production from the anaerobic co-digestion of the microalgae Scenedesmus quadricauda (S. quadricauda) and thickened waste activated sludge (TWAS). The concept was tested in bench-scale anaerobic digesters by varying the proportions of volatile solids (VS) loading from S. quadricauda and TWAS and two critical operational parameters, temperature and alkalinity. The CH(4) production for the various S. quadricauda and TWAS proportions ranged from 234 to 318 mL/g of chemical oxygen demand (COD) digested and 329 to 530 mL/g of VS digested at 35 degrees C. The reductions in total solids (TS), COD, and VS ranged from 25 to 44%, 46 to 53%, and 40 to 53%, respectively. Temperature had a significant effect on CH(4) production, lower temperatures greatly reduced CH(4) production. No significant difference in CH(4) production was observed for experiments conducted at alkalinity levels of 70, 1630, and 3200 mg/L as CaCO(3). PMID- 26803023 TI - Review of Water Consumption and Water Conservation Technologies in the Algal Biofuel Process. AB - Although water is one of the most critical factors affecting the sustainable development of algal biofuels, it is much less studied as compared to the extensive research on algal biofuel production technologies. This paper provides a review of the recent studies on water consumption of the algae biofuel process and presents the water conservation technologies applicable at different stages of the algal biofuel process. Open ponds tend to have much higher water consumption (216 to 2000 gal/gal) than photobioreactors (25 to 72 gal/gal). Algae growth accounts for the highest water consumption (165 to 2000 gal/gal) in the open pond system. Water consumption during harvesting, oil extraction, and biofuel conversion are much less compared with the growth stage. Potential water conservation opportunities include technology innovations and better management practices at different stages of algal biofuel production. PMID- 26803024 TI - Anaerobic Digestion of Algae Biomass to Produce Energy during Wastewater Treatment. AB - Water resource recovery facilities (WRRFs) are asked to improve both energy efficiency and nutrient removal efficacy. Integration of algaculture offers several potential synergies that could address these goals, including an opportunity to leverage anaerobic digestion at WRRFs. In this study, bench-scale experiments are used to measure methane yield during co-digestion of Scenedesmus dimorphus or mixed WRRF-grown algae with WRRF biosolids. The results indicate that normalized methane yield decreases with increasing algae content in a manner than can be reasonably well fit using linear regression (R(2) = 67%). It is thus possible to predict methane yield for any mixture of algae and biosolids based on the methane yield of the biosolids alone. Using revised methane yields, the energy return on investment of a typical WRRF increases from 0.53 (without algae) to 0.66 (with algae). Thus, algae-based wastewater treatment may hold promise for improving WRRF energy efficiency without compromising effluent quality. PMID- 26803025 TI - Cultivation of Chlorella vulgaris in Column Photobioreactor for Biomass Production and Lipid Accumulation. AB - Microalgae have been used as energy resources in recent decades to mitigate the global energy crisis. As the demand for pure microalgae strains for commercial use increases, designing an effective photobioreactor (PBR) for mass cultivation is important. Chlorella vulgaris, a local freshwater microalga, was used to study the algal biomass cultivation and lipid production using various PBR configurations (bubbling, air-lift, porous air-lift). The results show that a bubbling column design is a better choice for the cultivation of Chlorella vulgaris than an air-lift one. The highest biomass concentration in the bubbling PBR was 0.78 g/L while the air-lift PBR had a value of 0.09 g/L. Key operating parameters, including draft-tube length and bubbling flowrate, were then optimized based on biomass production and lipid yield. The highest lipid content was in the porous air-lift PBR and the air-lift PBR with shorter draft tube (35 cm) was also better than a longer one (50 cm) for algal cultivation, but the microalgae attachment on the inner tube of PBR always occurred. The highest biomass concentration could be produced under the highest gas flowrate of 2.7 L/min, whereas the lowest dry cell mass was under the lowest gas flowrate of 0.2 L/min. PMID- 26803026 TI - Evaluation of High Density Algal Cultivation for Secondary Wastewater Polishing. AB - This study evaluated the performance of an algal membrane bioreactor (A-MBR) for secondary wastewater effluent polishing and determined the membrane fouling behavior and dominance of algae in the A-MBR. The continuous flow A-MBR (effective volume = 7.2 L) was operated with low biomass wastage for more than 180 days, resulting in an average algal mixed liquor suspended solid concentration of 4922 mg/L. At the influent concentrations of 43 mg/L COD, 1.6 mg/L total phosphorus (TP), and 11.8 mg/L total nitrogen (TN), the effluent COD, TP and TN concentrations were 26 +/- 6 mg/L, 0.7 +/- 0.3 mg/L, and 9.6 +/- 1.2 mg/L, respectively. High-density algae cultivation facilitated P adsorption and chemical precipitation. However, the TN removal efficiency was only 14% because of low biomass wastage. Although bacteria represented less than 2% of the total biomass in the A-MBR, bacterial growth in the secondary wastewater effluent accelerated membrane fouling. PMID- 26803027 TI - Algal Growth Potential of Microcystis aeruginosa from Reclaimed Water. AB - Algal growth potential (AGP) of the cyanobacterium Microcystis aeruginosa (M. aeruginosa, NIES-298) using reclaimed water from various wastewater reclamation pilot plants was investigated to evaluate the feasibility of the reclaimed water usage for recreational purposes. After completing the coagulation and ultrafiltration processes, the concentrations of most contaminants in the reclaimed water were lower than the reuse guidelines for recreational water. However, M. aeruginosa successfully adapted to low levels of soluble reactive phosphorus (PO(3-)(4)) concentrations. The AGP values of M. aeruginosa decreased with the progression of treatment processes, and with the increases in the dilution volume. Also, both the AGP and chlorophyll-a values can be estimated a priori without conducting the AGP tests. Therefore, aquatic ecosystems in locations prone to environmental conditions favorable for the growth of M. aeruginosa require more rigorous nutrient management plans (e.g., reverse osmosis and dilution with clean water resources) to reduce the nutrient availability. PMID- 26803028 TI - Removal of Nitrogen and Phosphorus From Reject Water Using Chlorella vulgaris Algae After Partial Nitrification/Anammox Process. AB - Wastewater containing nutrients like ammonia, nitrite, nitrate and phosphates have been identified as the main cause of eutrophication in natural waters. Therefore, a suitable treatment is needed. In classical biological processes, nitrogen and phosphorus removal is expensive, especially due to the lack of biodegradable carbon, thus new methods are investigated. In this paper, the new possibility of nitrogen and phosphorus removal in side stream after the partial nitrification/Anammox process is proposed. Research was carried out in a lab scale vertical tubular photobioreactor (VTR) fed with real reject water, from dewatering of digested sludge, after partial nitrification/Anammox process from lab-scale sequencing batch reactor (SBR). Nitrogen and phosphorus concentrations were measured every three days. The average nitrogen and phosphorus loads were 0.0503 +/- 0.036 g N g(vss)/d and 0.0389 +/- 0.013 g P g(vss)/d accordingly. Results have shown that microalgae were able to efficiently remove nitrogen and phosphorus. The average nitrogen removal was 36.46% and phosphorus removal efficiency varied between 93 and 100%. PMID- 26803029 TI - The Selective Use of Hypochlorite to Prevent Pond Crashes for Algae-Biofuel Production. AB - Although algae-biofuels have many advantages including high areal productivity, algae can be preyed upon by amoebas, protozoans, ciliates, and rotifers, particularly in open pond systems. Thus, these higher organisms need to be controlled. In this study, Chlorella kessleri was used as the algal culture and Brachionus calyciflorus as the source of predation. The effect of sodium hypochlorite (bleach) was tested with the goal of totally inhibiting the rotifer while causing minor inhibition to the alga. The 24-hr LC(50) for B. calyciflorus in spring water was 0.198 mg Cl/L while the 24-hr LC(50) for C. kessleri was 0.321 mg Cl/L. However, chlorine dissipates rapidly as the algae serves as reductant. Results showed a chlorine dosage between 0.45 to 0.6 mg Cl/L and a dosing interval of two hours created the necessary chlorine concentrations to inhibit predation while letting the algae grow; thus giving algae farmers a tool to prevent pond crashes. PMID- 26803030 TI - Geochemical Signature of Natural Water Recharge in the Jungar Basin and Its Response to Climate. AB - This paper analyzed the physico-chemical characteristics of natural waters in a drainage system of the Jungar Basin, northwestern China to identify chemical evolution and recharge mechanisms of natural waters in an arid environment. The waters studied are different in mineralization, but are typically carbonate rivers and alkaline in nature. No Cl-dominated water type occurs, indicating an early stage of water evolution. Regolith and geomorphological parameters controlling ground-surface temperature may play a large role in the geological evolution of the water. Three main morphological and hydrological units are reflected in water physico-chemistry. Climate influences the salinization of natural waters substantially. Direct recharge from seasonal snow and ice-melt water and infiltration of rain to the ground are significant recharge processes for natural waters, but recharge from potential deep groundwater may be less important. The enrichment of ions in lakes has been mainly caused by evaporation rather than through the quality change of the recharged water. PMID- 26803031 TI - Preparation of Bamboo Chars and Bamboo Activated Carbons to Remove Color and COD from Ink Wastewater. AB - Bamboo chars and bamboo activated carbons prepared by steam activation were applied for ink wastewater treatment. Bamboo char at 800 degrees C was the best for the removal of color and chemical oxygen demand (COD) from ink wastewater compared to bamboo chars at 300 to 700 degrees C due to higher surface area and mesopore volume. Bamboo activated carbon at 600 degrees C (S600) was the best compared to bamboo activated carbon at 800 degrees C (S800), although S800 had larger surface area (1108 m(2)/g) than S600 (734 m(2)/g). S600 had higher mesopore volume (0.20 cm(3)/g) than S800 (0.16 cm(3)/g) and therefore achieved higher color and COD removal. All bamboo activated carbons showed higher color and COD removal efficiency than commercial activated carbon. In addition, S600 had the superior adsorption capacity for methylene blue (0.89 mmol/g). Therefore, bamboo is a suitable material to prepare adsorbents for removal of organic pollutants. PMID- 26803033 TI - Sustaining Reliability on Accountability Measures at The Johns Hopkins Hospital. AB - BACKGROUND: In 2012 Johns Hopkins Medicine leaders challenged their health system to reliably deliver best practice care linked to nationally vetted core measures and achieve The Joint Commission Top Performer on Key Quality Measures (r)program recognition and the Delmarva Foundation award. Thus, the Armstrong Institute for Patient Safety and Quality implemented an initiative to ensure that >=96% of patients received care linked to measures. Nine low-performing process measures were targeted for improvement-eight Joint Commission accountability measures and one Delmarva Foundation core measure. In the initial evaluation at The Johns Hopkins Hospital, all accountability measures for the Top Performer program reached the required >=95% performance, gaining them recognition by The Joint Commission in 2013. Efforts were made to sustain performance of accountability measures at The Johns Hopkins Hospital. METHODS: Improvements were sustained through 2014 using the following conceptual framework: declare and communicate goals, create an enabling infrastructure, engage clinicians and connect them in peer learning communities, report transparently, and create accountability systems. One part of the accountability system was for teams to create a sustainability plan, which they presented to senior leaders. To support sustained improvements, Armstrong Institute leaders added a project management office for all externally reported quality measures and concurrent reviewers to audit performance on care processes for certain measure sets. CONCLUSIONS: The Johns Hopkins Hospital sustained performance on all accountability measures, and now more than 96% of patients receive recommended care consistent with nationally vetted quality measures. The initiative methods enabled the transition of quality improvement from an isolated project to a way of leading an organization. PMID- 26803034 TI - Engaging Frontline Staff in Performance Improvement: The American Organization of Nurse Executives Implementation of Transforming Care at the Bedside Collaborative. AB - BACKGROUND: Process improvement stresses the importance of engaging frontline staff in implementing new processes and methods. Yet questions remain on how to incorporate these activities into the workday of hospital staff or how to create and maintain its commitment. In a 15-month American Organization of Nurse Executives collaborative involving frontline medical/surgical staff from 67 hospitals, Transforming Care at the Bedside (TCAB) was evaluated to assess whether participating units successfully implemented recommended change processes, engaged staff, implemented innovations, and generated support from hospital leadership and staff. METHODS: In a mixed-methods analysis, multiple data sources, including leader surveys, unit staff surveys, administrative data, time study data, and collaborative documents were used. RESULTS: All units reported establishing unit-based teams, of which >90% succeeded in conducting tests of change, with unit staff selecting topics and making decisions on adoption. Fifty-five percent of unit staff reported participating in unit meetings, and 64%, in tests of change. Unit managers reported substantial increase in staff support for the initiative. An average 36 tests of change were conducted per unit, with 46% of tested innovations sustained, and 20% spread to other units. Some 95% of managers and 97% of chief nursing officers believed that the program had made unit staff more likely to initiate change. Among staff, 83% would encourage adoption of the initiative. CONCLUSIONS: Given the strong positive assessment of TCAB, evidence of substantial engagement of staff in the work, and the high volume of innovations tested, implemented, and sustained, TCAB appears to be a productive model for organizing and implementing a program of frontline-led improvement. PMID- 26803035 TI - The Contribution of Sociotechnical Factors to Health Information Technology Related Sentinel Events. AB - BACKGROUND: An understanding of how health information technology (health IT) can contribute to sentinel events is necessary to learn how to safely implement and use health IT. An analysis was conducted to explore how health IT may contribute to adverse events that result in death or severe harm to the patient. METHODS: For 3,375 de-identified sentinel events voluntarily reported to The Joint Commission between January 1, 2010, and June 30, 2013, categorical and keyword queries were used to search for potential health IT-related events. Each of the identified events was reviewed on the basis of findings from root cause analyses (RCAs) to determine if health IT contributed to or caused the event, and if so, how and why. The contributing factors were classified using a composite of existing classification schemes. RESULTS: A total of 120 health IT-related sentinel events (affecting 125 patients) were identified. More than half resulted in patient death, 30% resulted in unexpected or additional care, and 11% resulted in permanent loss of function. The three most frequently identified event types were (1) medication errors, (2) wrong-site surgery (including the wrong side, wrong procedure, and wrong patient), and (3) delays in treatment. Contributing factors were most frequently associated with the human-computer interface, workflow and communication, and clinical content-related issues. CONCLUSIONS: The classification of health IT-related contributing factors indicates that health IT related events are primarily associated with the sociotechnical dimensions of human-computer interface, workflow and communication, and clinical content. Improved identification of health IT-related contributing factors in the context of the sociotechnical dimensions may help software developers, device manufacturers, and end users in health care organizations proactively identify vulnerabilities and hazards, ultimately reducing the risk of harm to patients. PMID- 26803036 TI - Redesigning the Patient Observer Model to Achieve Increased Efficiency and Staff Engagement on a Surgical Trauma Inpatient Unit. AB - BACKGROUND: Provision of safe and efficient observer care to inpatients whose behavior puts them at risk for injury is a clinically challenging and costly endeavor for hospitals. At Massachusetts General Hospital (MGH; Boston), process improvement strategies were deployed to provide staff with an improved clinical model for patient observation, unit-based responsibility for allocating resources, and strategies to maintain a safer environment. METHODS: In a surgical trauma unit at MGH, a team of nursing leaders and clinicians created an innovative process to identify, assess, and develop best practices for ensuring patient safety in the hospital environment. Patients with delirium were identified as the most prevalent and concerning patient group, and specific interventions were developed to address their unique needs. From December 2012 through June 2014, the team successfully piloted the best practices (July 16, 2013-September 30, 2013) and implemented them. RESULTS: The baseline outcome metric of patient observer direct-care hours decreased from a median of 208 hours/week (January 1, 2012-July 13, 2013) to a median of 112 hours/week (July 14, 2013-June 28, 2014); a 46% decrease in utilization. Fall rate (falls per 1,000 patient-days) remained unchanged postimplementation, and staff satisfaction with the patient observer model increased from 9% to 72%, while costs associated with providing observer care remained stable. CONCLUSIONS: Providing the inpatient unit staff with the knowledge and tools needed to optimally manage patients with at-risk behaviors, including delirium, significantly decreased the number of staff hours spent at the bedside providing observation, did not negatively affect the unit fall rate, and increased staff engagement at no additional expense to the unit. PMID- 26803037 TI - Recommendations and Low-Technology Safety Solutions Following Neuromuscular Blocking Agent Incidents. AB - BACKGROUND: Neuromuscular blocking agents (NMBs) are high-risk medications used to facilitate endotracheal intubation and artificial ventilation. In an incident at a metropolitan tertiary referral and teaching public hospital in Australia, a neurosurgical patient became unresponsive at the start of surgery. It was determined that cisatracurium was administered in error in place of midazolam; the patient was ventilated and the emergency surgery continued. Two additional non-operating room (OR) drug-swap cases involving cisatracurium were reported within 12 months of this event, resulting in a comprehensive review of NMB safety. METHODS: A root cause analysis (RCA) resulted in multiple interventions to decrease the risk of selection and administration errors: (1) review of NMB packaging and introduction of in-house NMB labeling by pharmacy procurement staff before distribution; (2) implementation of a medication administration in anesthetics guideline with ongoing education; (3) audit of storage with removal of NMBs; (4) review of new products by medication safety pharmacists and a senior anesthetist before distribution; and (5) use of red-barrel syringes for administering NMBs was expanded to all areas using NMBs to minimize syringe-swap incidents. RESULTS: In the four years since full implementation of interventions, there have been no reports of cisatracurum selection errors. An incident of atracurium administration resulted in further recommendations for review of OR cart storage. Ongoing monitoring via medication safety walkrounds, by OR staff, by the perioperative pharmacist, and through the hospital's medication incident monitoring system has not detected any further NMB incidents. CONCLUSIONS: Technological solutions have been shown to decrease the risk of NMB errors, yet multifaceted low-technology solutions may be an effective, cheaper alternative. PMID- 26803038 TI - Lessons Learned on a Journey from Surgeon to Chief Quality Officer. PMID- 26803039 TI - Fresh Start. PMID- 26803040 TI - Just-in-Time Training: A Novel Approach to Quality Improvement Education. AB - Just-in-time training (JITT) is accepted in medical education as a training method for newer concepts or seldom-performed procedures. Providing JITT to a large nursing staff may be an effective method to teach quality improvement (QI) initiatives. We sought to determine if JITT could increase knowledge of a specific nutrition QI initiative. Members of the nutrition QI team interviewed staff using the Frontline Contextual Inquiry to assess knowledge regarding the specific QI project. The inquiry was completed pre- and post-JITT. A JITT educational cart was created, which allowed trainers to bring the educational information to the bedside for a short, small group educational session. The results demonstrated a marked improvement in the knowledge of the frontline staff regarding our Vermont Oxford Network involvement and the specifics of the nutrition QI project. Just-in-time training can be a valuable and effective method to disseminate QI principles to a large audience of staff members. PMID- 26803041 TI - Improved Cognitive Development in Preterm Infants with Shared Book Reading. AB - PURPOSE: To examine the effect of shared book reading on the cognitive development of children born preterm and to determine what factors influence shared book reading in this population. DESIGN: Secondary analysis using the Early Childhood Longitudinal Study-Birth Cohort, a large, nationally representative survey of children born in the United States in 2001. SAMPLE: One thousand four hundred singleton preterm infants (22-36 weeks gestation). MAIN OUTCOME VARIABLE: Cognitive development measured using the Bayley Mental Scale score from the Bayley Scales of Infant Development Research Edition. RESULTS: Adjusting for neonatal, maternal, and socioeconomic characteristics, reading aloud more than two times a week is associated with higher cognitive development scores in two-year-old children born preterm (p < .001). Race/ethnicity and maternal education affect how often parents read to their children. Shared book reading holds potential as an early developmental intervention for this population. PMID- 26803042 TI - Simulation to Standardize Patient Care and Maintain Procedural Competency. AB - Simulation-based training is a means to teach procedural skills and to help advanced practice providers maintain procedural competency and credentialing. There is growing recognition of the importance of requiring providers to demonstrate competency of invasive procedures in a simulated environment prior to performing these high-risk procedures on patients. This article describes the development and implementation of the simulation procedural program at the University of Rochester Medical Center. In addition to contributing to the education of our providers, such a program can lead to improved patient quality, safety, and outcomes through the standardization of patient care. The innovative use of simulation can lead to effective heath care education and improvement in patient safety. PMID- 26803043 TI - Pathophysiology of the Cardiovascular System and Neonatal Hypotension. AB - Hypotension is common in low birth weight neonates and less common in term newborns and is associated with significant morbidity and mortality. Determining an adequate blood pressure in neonates remains challenging for the neonatal nurse because of the lack of agreed-upon norms. Values for determining norms for blood pressure at varying gestational and postnatal ages are based on empirical data. Understanding cardiovascular pathophysiology, potential causes of hypotension, and assessment of adequate perfusion in the neonatal population is important and can assist the neonatal nurse in the evaluation of effective blood pressure. This article reviews cardiovascular pathophysiology as it relates to blood pressure and discusses potential causes of hypotension in the term and preterm neonate. Variation in management of hypotension across centers is discussed. Underlying causes and pathophysiology of hypotension in the neonate are described. PMID- 26803044 TI - Teaching Nurses About Research. AB - The purpose of this article is to provide educators with teaching and learning strategies aimed at engaging participants in learning more about research and related topics, such as quality improvement and evidence-based practice. This article includes various creative strategies. PMID- 26803045 TI - Hydrocortisone for Treatment of Hypotension in the Newborn. AB - Newborns, and especially premature newborns, are at significant risk for developing hypotension in the first week or two after birth. The etiology of hypotension in the newborn may vary, but the very low birth weight and extremely low birth weight preterm infants are less likely to respond to conventional cardiovascular support when they develop hypotension. This article reviews the least conventional treatment using hydrocortisone for hypotension that is refractory to conventional volume replacement and/or vasopressor medications with the underlying assumption that sick and premature newborns have a relative or measured adrenal insufficiency. The addition of hydrocortisone in the treatment of hypotension in the newborn is becoming more common but is not universally advocated. However, the supportive evidence is growing, and, as reviewed, use of hydrocortisone requires judicious and cautious regard. PMID- 26803047 TI - NICU Helping Hands: Supporting Families Through the Whole Journey. AB - Parents are the pure focus of NICU Helping Hands (NHH), an organization that started in Texas in 2011. Whether a family is in need of the basic necessities, support, or even a special burial gown for their infant, NHH is there. Learn how this nonprofit has gone from regional to international star in a short amount of time and how it can help your NICU. PMID- 26803050 TI - Therapeutic drug monitoring in neonates. AB - Therapeutic drug monitoring (TDM) aims to integrate drug measurement results into clinical decision making. The basic rules apply when using TDM in neonates (aminoglycosides, vancomycin, phenobarbital, digoxin), but additional factors should also be taken into account. First, due to both pharmacokinetic variability and non-pharmacokinetic factors, the correlation between dosage and concentration is poor in neonates, but can be overcome with the use of more complex, validated dosing regimens. Second, the time to reach steady state is prolonged, especially when no loading dose is used. Consequently, the timing of TDM sampling is important in this population. Third, the target concentration may be uncertain (vancomycin) or depend on specific factors (phenobarbital during whole body cooling). Finally, because of differences in matrix composition (eg, protein, bilirubin), assay-related inaccuracies may be different in neonates. We anticipate that complex validated dosing regimens, with subsequent TDM sampling and Bayesian forecasting, are the next step in tailoring pharmacotherapy to individual neonates. PMID- 26803051 TI - Cannabidiol oil in the treatment of super refractory status epilepticus. A case report. PMID- 26803052 TI - Limited efficacy of the ketogenic diet in the treatment of highly refractory epileptic spasms. AB - PURPOSE: Numerous studies have suggested that the ketogenic diet is effective in the treatment of epileptic spasms, even in refractory cases. However, there has been very limited demonstration of prompt and complete (video-EEG confirmed) response. We set out to describe our center's experience with the ketogenic diet in the treatment of children with highly refractory epileptic spasms, with rigorous seizure outcome assessment. METHOD: Children treated with the ketogenic diet for epileptic spasms between April, 2010 and June, 2014 were retrospectively identified. Seizure burden was tabulated at baseline and after 1, 3, 6, and 12 months of ketogenic diet exposure. Adverse events were similarly ascertained. RESULTS: We identified a cohort of 22 consecutive patients who received ketogenic diet therapy, with median age of onset of epileptic spasms of 5.2 (IQR 2.0-9.0) months, with diet initiation beginning a median of 26.4 (12.5-38.7) months after onset, and following a median of 7 (IQR 5-7) treatment failures. Only 2 patients exhibited a complete response during ketogenic diet exposure, and response was more reasonably attributed to alternative therapies in both cases. A modest early reduction in seizure frequency was not sustained beyond 1 month of diet exposure. The diet was well tolerated, and continued in 6 patients with subjective and/or partial response. CONCLUSION: In contrast to prior studies reporting substantial efficacy of the ketogenic diet, our findings suggest limited efficacy, albeit in a highly refractory cohort. Prospective studies in both refractory and new-onset populations, with both video-EEG confirmation of response and rigorous cognitive outcome assessment, would be of great value to more clearly define the utility of the ketogenic diet in the treatment of epileptic spasms. PMID- 26803053 TI - Hippocampal internal architecture and postoperative seizure outcome in temporal lobe epilepsy due to hippocampal sclerosis. AB - PURPOSE: Semi-quantitative analysis of hippocampal internal architecture (HIA) on MRI has been shown to be a reliable predictor of the side of seizure onset in patients with temporal lobe epilepsy (TLE). In the present study, we investigated the relationship between postoperative seizure outcome and preoperative semi quantitative measures of HIA. METHODS: We determined HIA on high in-plane resolution preoperative T2 short tau inversion recovery MR images in 79 patients with presumed unilateral mesial TLE (mTLE) due to hippocampal sclerosis (HS) who underwent amygdalohippocampectomy and postoperative follow up. HIA was investigated with respect to postoperative seizure freedom, neuronal density determined from resected hippocampal specimens, and conventionally acquired hippocampal volume. RESULTS: HIA ratings were significantly related to some neuropathological features of the resected hippocampus (e.g. neuronal density of selective CA regions, Wyler grades), and bilaterally with preoperative hippocampal volume. However, there were no significant differences in HIA ratings of the to-be-resected or contralateral hippocampus between patients rendered seizure free (ILAE 1) compared to those continuing to experience seizures (ILAE 2 5). CONCLUSIONS: This work indicates that semi-quantitative assessment of HIA on high-resolution MRI provides a surrogate marker of underlying histopathology, but cannot prospectively distinguish between patients who will continue to experience postoperative seizures and those who will be rendered seizure free. The predictive power of HIA for postoperative seizure outcome in non-lesional patients with TLE should be explored. PMID- 26803054 TI - Autopsy findings of a patient with acute encephalitis and refractory, repetitive partial seizures. PMID- 26803055 TI - Oncolytic and immunologic cancer therapy with GM-CSF-armed vaccinia virus of Tian Tan strain Guang9. AB - Targeted oncolytic vaccinia viruses are being developed as a novel strategy in cancer therapy. Arming vaccinia viruses with immunostimulatory cytokines can enhance antitumor efficacy. Such engineered oncolytic viruses, like JX-594, a Wyeth strain vaccinia virus modified with human granulocyte-macrophage colony stimulating factor (GM-CSF), have shown promising results and have proceeded rapidly in clinical trials. However, the oncolytic potential of the Chinese vaccine strain Tian Tan (VTT) has not been explored. In this study, we constructed a targeted oncolytic vaccinia virus of Tian Tan strain Guang9 (VG9) expressing murine GM-CSF (VG9-GMCSF) and evaluated the antitumor effect of this recombinant vaccinia virus in a murine melanoma model. In vitro, viral replication and cytotoxicity of VG9-GMCSF was as potent as VG9; in vivo, VG9 GMCSF significantly inhibited the growth of subcutaneously implanted melanoma tumors, prolonged the survival of tumor-bearing mice, and produced an antitumor cytotoxic response. Such antitumor effect may be due to the lytic nature of virus as well as the stimulation of immune activity by GM-CSF production. Our results indicate that VG9-GMCSF induces strong tumoricidal activity, providing a potential therapeutic strategy for combating cancer. PMID- 26803056 TI - Dendritic cell based immunotherapy using tumor stem cells mediates potent antitumor immune responses. AB - Cancer stem cells (CSCs) are demonstrated to be usually less sensitive to conventional methods of cancer therapies, resulting in tumor relapse. It is well known that an ideal treatment would be able to selectively target and kill CSCs, so as to avoid the tumor reversion. The aim of our present study was to evaluate the effectiveness of a dendritic cell (DC) based vaccine against CSCs in a mouse model of malignant melanoma. C57BL/6 mouse bone marrow derived DCs pulsed with a murine melanoma cell line (B16F10) or CSC lysates were used as a vaccine. Immunization of mice with CSC lysate-pulsed DCs was able to induce a significant prophylactic effect by a higher increase in lifespan and obvious depression of tumor growth in tumor bearing mice. The mice vaccinated with DCs loaded with CSC lysate were revealed to produce specific cytotoxic responses to CSCs. The proliferation assay and cytokine (IFN-gamma and IL-4) secretion of mice vaccinated with CSC lysate-pulsed DCs also showed more favorable results, when compared to those receiving B16F10 lysate-pulsed DCs. These findings suggest a potential strategy to improve the efficacy of DC-based immunotherapy of cancers. PMID- 26803058 TI - beta2-adrenergic receptor signaling promotes pancreatic ductal adenocarcinoma (PDAC) progression through facilitating PCBP2-dependent c-myc expression. AB - The beta2-adrenergic receptor (beta2-AR) plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) progression. In this report, we identified poly(rC) binding protein 2 (PCBP2) as a novel binding partner for beta2-AR using immunoprecipitation-mass spectrometry (IP-MS) approach. The association between beta2-AR and PCBP2 was verified using reciprocal immunoprecipitation. Importantly, we found significant interaction and co-localization of the two proteins in the presence of beta2-AR agonist in Panc-1 and Bxpc3 PDAC cells. beta2-AR-induced recruitment of PCBP2 led to augmented protein level of c-myc in PDAC cells, likely as a result of enhanced internal ribosome entry segment (IRES) mediated translation of c-myc. The activation of beta2-AR accelerated cell proliferation and colony formation, while knockdown of PCBP2 or c-myc restrained the effect. Furthermore, overexpression of PCBP2 was observed in human PDAC cell lines and tissue specimens compared to the normal pancreatic ductal epithelial cells and the non-cancerous tissues respectively. Overexpression of beta2-AR and PCBP2 was associated with advanced tumor stage and significantly worsened prognosis in patients with PDAC. Our results elucidate a new molecular mechanism by which beta2-AR signaling facilitates PDAC progression through triggering PCBP2 dependent c-myc expression. PMID- 26803057 TI - SKF-96365 activates cytoprotective autophagy to delay apoptosis in colorectal cancer cells through inhibition of the calcium/CaMKIIgamma/AKT-mediated pathway. AB - Store-operated Ca(2+) entry (SOCE) inhibitors are emerging as an attractive new generation of anti-cancer drugs. Here, we report that SKF-96365, an SOCE inhibitor, exhibits potent anti-neoplastic activity by inducing cell-cycle arrest and apoptosis in colorectal cancer cells. In the meantime, SKF-96365 also induces cytoprotective autophagy to delay apoptosis by preventing the release of cytochrome c (cyt c) from the mitochondria into the cytoplasm. Mechanistically, SKF-96365 treatment inhibited the calcium/calmodulin-dependent protein kinase IIgamma (CaMKIIgamma)/AKT signaling cascade in vitro and in vivo. Overexpression of CaMKIIgamma or AKT abolished the effects of SKF-96365 on cancer cells, suggesting a critical role of the CaMKIIgamma/AKT signaling pathway in SFK-96365 induced biological effects. Moreover, Hydroxychloroquine (HCQ), an FDA-approved drug used to inhibit autophagy, could significantly augment the anti-cancer effect of SFK-96365 in a mouse xenograft model. To our best knowledge, this is the first report to demonstrate that calcium/CaMKIIgamma/AKT signaling can regulate apoptosis and autophagy simultaneously in cancer cells, and the combination of the SOCE inhibitor SKF-96365 with autophagy inhibitors represents a promising strategy for treating patients with colorectal cancer. PMID- 26803059 TI - Stimulus-dependent amygdala involvement in affective theory of mind generation. AB - Successful social interaction requires knowledge about another person's emotional states, represented in an affective theory of mind (ToM). This information can be acquired either directly or indirectly, i.e., by observing emotional facial expressions (EFE) or indirectly by inferring emotions through cognitive perspective taking. Therefore, it is of great interest how the function of the cortical ToM network and the limbic system in affective ToM depends on the presence of facial expressions. We addressed this question in a functional magnetic resonance imaging (fMRI) study. The experimental paradigm applied a well established ToM cartoon task to test functional effects of EFE on the activation of the amygdala and the anterior ToM network during affective ToM judgments. During the task, 22 healthy participants had to judge the changes of the emotional state of the stories protagonist in the presence or absence of EFE. After quality control, 21 data sets entered the final analyses. The presence of EFE during affective ToM judgments was associated with shorter reaction times as well as increased activation of the right amygdala, most probably located in the basolateral nucleus (BLA), coincident with reduced activation of ToM-related regions of the prefrontal cortex. Psychophysiological interactions (PPI) revealed EFE-dependent modulation of connectivity between the right BLA and the contralateral ToM network regions. In combination with the functional interaction of EFE and affective ToM in the right amygdala, our data suggest a complementary but parallel organization of EFE processing and affective ToM. In this framework, the amygdala seems to act as an EFE detector when affective ToM judgments are demanded. Additionally, the facts that EFE induced exclusively right-sided amygdala activation and modulated the connectivity with the contralateral ToM network support the idea of a functional lateralization of stimulus driven components of affective ToM. PMID- 26803060 TI - Ventral striatum activity when watching preferred pornographic pictures is correlated with symptoms of Internet pornography addiction. AB - One type of Internet addiction is excessive pornography consumption, also referred to as cybersex or Internet pornography addiction. Neuroimaging studies found ventral striatum activity when participants watched explicit sexual stimuli compared to non-explicit sexual/erotic material. We now hypothesized that the ventral striatum should respond to preferred pornographic compared to non preferred pornographic pictures and that the ventral striatum activity in this contrast should be correlated with subjective symptoms of Internet pornography addiction. We studied 19 heterosexual male participants with a picture paradigm including preferred and non-preferred pornographic materials. Subjects had to evaluate each picture with respect to arousal, unpleasantness, and closeness to ideal. Pictures from the preferred category were rated as more arousing, less unpleasant, and closer to ideal. Ventral striatum response was stronger for the preferred condition compared to non-preferred pictures. Ventral striatum activity in this contrast was correlated with the self-reported symptoms of Internet pornography addiction. The subjective symptom severity was also the only significant predictor in a regression analysis with ventral striatum response as dependent variable and subjective symptoms of Internet pornography addiction, general sexual excitability, hypersexual behavior, depression, interpersonal sensitivity, and sexual behavior in the last days as predictors. The results support the role for the ventral striatum in processing reward anticipation and gratification linked to subjectively preferred pornographic material. Mechanisms for reward anticipation in ventral striatum may contribute to a neural explanation of why individuals with certain preferences and sexual fantasies are at-risk for losing their control over Internet pornography consumption. PMID- 26803061 TI - Dynamic coupling of complex brain networks and dual-task behavior. AB - Multi-tasking is a familiar situation where behavioral performance is often challenged. To date, fMRI studies investigating the neural underpinning of dual task interference have mostly relied on local brain activation maps or static brain connectivity networks. Here, based on task fMRI we explored how fluctuations in behavior during concurrent performance of a visuospatial and a speech task relate to alternations in the topology of dynamic brain connectivity networks. We combined a time-resolved functional connectivity and complex network analysis with a sliding window approach applied to the trial by trial behavioral responses to investigate the coupling between dynamic brain networks and dual task behavior at close temporal proximity. Participants showed fluctuations in their dual-task behavior over time, with the accuracy in the component tasks being statistically independent from one another. On the global level of brain networks we found that dynamic changes of network topology were differentially coupled with the behavior in each component task during the course of dual tasking. While momentary decrease in the global efficiency of dynamic brain networks correlated with subsequent increase in visuospatial accuracy, better speech performance was preceded by higher global network efficiency and was followed by an increase in between-module connectivity over time. Additionally, dynamic alternations in the modular organization of brain networks at the posterior cingulate cortex were differentially predictive for the visuospatial as compared to the speech accuracy over time. Our results provide the first evidence that, during the course of dual-tasking, each component task is supported by a distinct topological configuration of brain connectivity networks. This finding suggests that the failure of functional brain connectivity networks to adapt to an optimal topology supporting the performance in both component tasks at the same time contributes to the moment to moment fluctuations in dual-task behavior. PMID- 26803062 TI - Resuscitation highlights in 2015. PMID- 26803082 TI - New Practice Models Gaining Traction. PMID- 26803063 TI - Life-threatening ventricular tachyarrhythmias in the cardiology department: Implications for appropriate prescription of telemetry monitoring. AB - BACKGROUND: in-hospital life-threatening ventricular arrhythmias (LT-VA) may complicate the course of cardiovascular patients. We aimed to assess the incidence, circumstances, determinants, and outcome of in-hospital LT-VA in order to help clinicians in prescribing appropriate levels of monitoring. METHODS: the study population consisted of all 10,741 consecutive patients (65 +/- 15 years, 67.7% males) admitted to a cardiology department in 2009-2014. Terminally ill patients and those with primary arrhythmia diagnosis were excluded. The composite end-point included sudden arrhythmic death, ventricular fibrillation, unstable ventricular tachycardia and appropriate ICD shock unrelated to invasive interventions. RESULTS: the incidence of LT-VA was 0.6%, with no differences regarding age, gender and primary diagnosis of coronary artery disease between patients with and without LT-VA. The incidence of LT-VA was significantly higher (1.2% versus 0.1%, p<0.001) among urgent compared with elective admissions and among patients with left ventricular ejection fraction (LV-EF) <45% (1.7% versus 0.2%, p<0.001). At multivariable analysis, urgent admission and LV-EF <45%, but not primary diagnosis of coronary artery disease, remained independent predictors of LT-VA. At the time of the event, 97.1% fulfilled either class I or class II indications for telemetry monitoring according to the American Heart Association guidelines. Survival to discharge with good neurological status was 70.6%. CONCLUSIONS: acutely ill patients with heart failure and LV systolic dysfunction showed the highest rate of LT-VAs, regardless of the underlying cardiac disease (ischemic or non-ischemic). Current guidelines demonstrated high sensitivity in identifying patients at risk. These findings may favor proper utilization of telemetry monitoring resources. PMID- 26803083 TI - The Changing Landscape of Community-Based Pharmacy Practice Part 2 of 2. AB - Increasingly, care for elderly individuals with chronic diseases who take multiple medications is being provided in community-based settings. Pharmacists and other health care providers are responding to this trend by collaborating in new, innovative ways such as practicing in physicians' offices or partnering with community pharmacies. The goal is to care for these elderly patients and help them effectively manage their medications where they live. These changes are having another result-they are transforming what patients, insurers, and other health providers expect from pharmacists who are helping to manage the medications and health care of older adults. PMID- 26803084 TI - Aspirin Use for the Primary Prevention of Cardiovascular Disease in the Elderly. AB - OBJECTIVE: This article aims to use the available evidence assessing aspirin for primary prevention of cardiovascular (CV) events in the elderly to determine its appropriate use. DATA SOURCES: A literature search of clinical trials and meta analyses was conducted using MEDLINE and PubMed with the search terms aspirin, bleeding, CV events, elderly, geriatrics, hemorrhage, myocardial infarction (MI), primary prevention, and stroke. STUDY SELECTION/DATA EXTRACTION: Twelve hundred fourteen (1,214) articles were initially found, and 55 were reviewed. These articles assessed the use of aspirin for primary prevention of CV events. Only trials comparing aspirin with placebo, a non-antiplatelet, or a non-anticoagulant were included in this review. Of the articles reviewed, 10 met the stated criteria. DATA SYNTHESIS: It is well documented that the risk of CV events increases as patients age. Primary prevention of these events with aspirin may be beneficial in some patients. Currently, a specific recommendation for the use of aspirin for primary prevention in the geriatric population is not available. This paper reviews the available evidence for primary prevention of CV disease. This population is under-represented in the literature, making it challenging to apply the study findings. CONCLUSION: Aspirin may be considered for the primary prevention of CV events in the elderly population. Because of the lack of data in patients 80 years of age and older, it is difficult to make a decision on the initiation of aspirin therapy in this population. Additional research is necessary to better balance the risk versus benefit of this treatment option. PMID- 26803085 TI - Herpes Zoster Vaccine in the Long-Term Care Setting: A Clinical and Logistical Conundrum. AB - Advancing age is associated with an increased risk of herpes zoster (shingles) infection and latent effects such as postherpetic neuralgia. The herpes zoster vaccine is recommended in those 60 years of age and older and has been shown to prevent both the primary disease and associated complications. While this recommendation applies to those living in long-term care facilities, there is little clinical evidence to support use in this population. Additionally, there are logistical barriers that may complicate the use of the vaccine. The article examines the evidence for vaccinating residents in long-term care facilities and discusses logistical barriers to vaccination. Pharmacists and providers may consider life expectancy and other factors when evaluating which patients should receive the vaccination. PMID- 26803086 TI - Motivational Interviewing to Increase Postdischarge Antibiotic Adherence in Older Adults with Pneumonia. AB - OBJECTIVE: To evaluate the impact of a pharmacist-led, motivational interviewing on antibiotic adherence following discharge in older adults with pneumonia. SETTING: Inpatient medical wards in a large tertiary academic medical center. PRACTICE DESCRIPTION: Older adults diagnosed with pneumonia were enrolled from December 1, 2013, to August 1, 2014, at Yale-New Haven Hospital. PRACTICE INNOVATION: Motivational interviewing-a patient-centered method of communication has gained recognition as a tool that can aid pharmacists in addressing negative health behaviors (e.g., medication adherence, health screenings, substance abuse during counseling sessions). However, the potential role of motivational interviewing in older adults to improve medication adherence during transitions of care is not clear. In this study, in addition to standard discharge care, older adults hospitalized with pneumonia who were randomized to the intervention group received enhanced care: pharmacist-led motivational interviewing. MAIN OUTCOME MEASUREMENTS: Evaluation of adherence to prescribed antibiotic regimens and patient satisfaction with the motivational interviewing, enhanced-care session. RESULTS: Ultimately, 87% of patients in the intervention group (n = 16) compared with 64% of patients in the control group (n = 14) were adherent to their antibiotic regimens. Patient satisfaction with the motivational interviewing intervention was high. CONCLUSION: Pharmacist-led motivational interviewing sessions have the potential to positively influence antibiotic adherence rates and patient satisfaction. PMID- 26803087 TI - Transitional Care Units: Expanding the Role of Pharmacists Providing Patient Care. AB - OBJECTIVE: To describe two innovative practice models that expand pharmacy services within a nursing facility's transitional care unit (TCU) to meet the needs of patients transitioning to subacute or community care. SETTING: TCU in a hospital-based vs. a community-based facility. PRACTICE DESCRIPTION: The two TCUs involved in these practices differ in that one is hospital-owned and the other is community-based and run by a nonprofit organization. Patients involved in the models are those who have been admitted to the TCU from a hospital and will eventually return home to the community. PRACTICE INNOVATION: Pharmacy services beyond the federally required, monthly drug regimen review are described, including pharmacist-conducted medication reconciliation, which identifies the drugs the patient is taking on admission and those prescribed before discharge from the TCU. Post-TCU discharge follow-up is also provided via telephone call or home visit. MAIN OUTCOME MEASUREMENTS: Description of practice models. RESULTS: Timely medication reconciliation and review on TCU admission is key to safe medication use during transitions of care. Incorporating pharmacy students and residents can promote awareness of the service. Partnerships with health systems and colleges or schools of pharmacy can provide financial support of these innovative practice models. CONCLUSION: Pharmacist-driven medication reconciliation and review can improve medication safety across transitions of care involving TCUs. Research is needed to evaluate the impact of these models on outcomes before they are replicated. PMID- 26803088 TI - Rising Drug Prices and PBM Practices in the Spotlight. PMID- 26803089 TI - Establishing Intervention Fidelity of an Oral Motor Intervention for Preterm Infants. AB - PURPOSE: To establish intervention fidelity of the premature infant oral motor intervention (PIOMI) Design and sample: A rating tool was developed and tested for interrater reliability before being used to test the fidelity of intervention behaviors. A purposeful convenience sample of three users was recruited to perform the intervention under direct observation. MAIN OUTCOME VARIABLES: Three types of reliabilities were calculated: (1) interrater reliability to test the rating tool, followed by (2) interuser reliability, and (3) test-retest reliabilities to test the intervention behaviors of several registered nurses (RNs) over repeated performances of the intervention. RESULTS: The rating tool demonstrated a high interrater reliability (97.57 percent), indicating its accuracy for systematically rating the specific intervention behaviors. Subsequently, the rating tool was used to determine interuser and test-retest performances of the PIOMI and resulted in high reliabilities (97.59 percent and 97.58 percent, respectively). This demonstrates that the intervention can be reliably delivered as prescribed, supporting intervention fidelity. PMID- 26803090 TI - Probiotics for Preterm Infants: A Premature or Overdue Necrotizing Enterocolitis Prevention Strategy? AB - Common among preterm, very low birth weight (VLBW) and extremely low birth weight (ELBW) infants, necrotizing enterocolitis (NEC) is a gastrointestinal, infectious disease that remains a leading cause of morbidity and mortality among this high risk population. To combat this devastating condition, research efforts have been redirected from treatment toward prevention strategies. Although there are several proposed risk-reduction strategies, one intervention gaining support is the administration of prophylactic enteral probiotics. Regardless of growing evidentiary support and a benign safety profile, neonatal providers have yet to embrace this therapy. This article provides an overview of the proposed benefits of probiotics, focusing on their role as a NEC prevention strategy. A review of several sentinel research studies targeting preterm, VLBW, and ELBW infants is provided. Considerations for ongoing research are reviewed. Finally, two evidence based NEC prevention probiotics protocols are presented. PMID- 26803091 TI - Development of Home Educational Materials for Families of Preterm Infants. AB - INTRODUCTION: Parent educational materials describing infant positioning for a home program are vital in supplementing NICU discharge instructions and promoting parent confidence. PURPOSE: To document the process of developing a brochure and DVD of a positioning program, using evidence-based practice and NICU expert feedback. METHODS: A trifold brochure and companion DVD were developed to demonstrate infant positioning to parents of premature infants for a home developmental program following NICU discharge. A standard process of development was followed for the brochure and DVD script and production. The process included review and comment by eight NICU professionals and several revisions. RESULTS: Content of the brochure and DVD and the process entailed in their development is described. Guidelines outlining the process for development of educational materials for families are provided. CONCLUSION: Creation of multimedia educational materials for parents of infants who are NICU graduates requires a multistep process to ensure usefulness and validity. PMID- 26803092 TI - Opioid Analgesics for Sedation and Analgesia During Mechanical Ventilation. AB - Neonates are exposed to repetitive pain and stress during their stay in a NICU, which can lead to chronic complications related to their neurodevelopment and neurobehavior. Approximately 20 percent of all neonates in a NICU are intubated, mechanically ventilated, and require suctioning, which can cause both acute and chronic pain. Pain management in the neonate can be challenging. Nurses and other caregivers need to be well trained to assess pain in the neonate to effectively identify and provide appropriate pain management strategies. There is a lack of evidence to support routine administration of opiates in the neonate. As with any medication, the possibility of short- and long-term adverse reactions must be considered. Nonpharmacologic therapy should be used as much as possible. PMID- 26803093 TI - Noonan Syndrome Complicated by Primary Pulmonary Lymphangiectasia. AB - Noonan syndrome is a genetic disorder that has several features common to other conditions, making diagnosis a challenge. This column summarizes the case of a neonate with an atypical presentation of Noonan syndrome involving a fatal type of lymphangiectasia resulting in persistent pleural effusions. Radiographic features of this condition are presented along with the complexities of diagnosis and treatment. PMID- 26803094 TI - Neonatal Pressure Ulcer Prevention. AB - The incidence of pressure ulcers in acutely ill infants and children ranges up to 27 percent in intensive care units, with a range of 16-19 percent in NICUs. Anatomic, physiologic, and developmental factors place ill and preterm newborns at risk for skin breakdown. Two case studies illustrate these factors, and best practices for pressure ulcer prevention are described. PMID- 26803096 TI - News of the Academy of Neonatal Nursing. PMID- 26803098 TI - A New Evaluation Method for Groundwater Quality Applied in Guangzhou Region, China: Using Fuzzy Method Combining Toxicity Index. AB - Groundwater quality assessment is essential for drinking from a security point of view. In this paper, a new evaluation method called toxicity combined fuzzy evaluation (TCFE) has been put forward, which is based on the fuzzy synthetic evaluation (FSE) method and the toxicity data from Agency for Toxic Substances and Disease Registry. The comparison of TCFE and FSE in the groundwater quality assessment of Guangzhou region also has been done. The assessment results are divided into 5 water quality levels; level I is the best while level V is the worst. Results indicate that the proportion of level I, level II, and level III used by the FSE method was 69.33% in total. By contrast, this proportion rose to 81.33% after applying the TCFE method. In addition, 66.7% of level IV samples in the FSE method became level I (50%), level II (25%), and level III (25%) in the TCFE method and 29.41% of level V samples became level I (50%) and level III (50%). This trend was caused by the weight change after the combination of toxicity index. By analyzing the changes of different indicators' weight, it could be concluded that the better-changed samples mainly exceeded the corresponding standards of regular indicators and the deteriorated samples mainly exceeded the corresponding standards of toxic indicators. The comparison between the two results revealed that the TCFE method could represent the health implications of toxic indicators reasonably. As a result, the TCFE method is more scientific in view of drinking safety. PMID- 26803099 TI - Influence of Water Table Depth on Pore Water Chemistry and Trihalomethane Formation Potential in Peatlands. AB - Drained peatland catchments are reported to produce more colored, dissolved organic carbon (DOC)-rich water, presenting problems for potable water treatment. The blocking of peatland drainage ditches to restore the water table is increasingly being considered as a strategy to address this deterioration in water quality. However, the effect of ditch blocking on the potential of DOC to form trihalomethanes (THMs) has not been assessed. In this study, the effect of peat rewetting on pore water DOC concentration and characteristics (including THM formation potential [THMFP]) was assessed over 12 months using peat cores collected from two drained peatland sites. The data show little evidence of differences in DOC concentration or characteristics between the different treatments. The absence of any difference in the THMFP of pore water between treatments suggests that, in the short term at least, ditch blocking may not have an effect on the THMFP of waters draining peatland catchments. PMID- 26803100 TI - Removal Rate of Organic Matter Using Natural Cellulose via Adsorption Isotherm and Kinetic Studies. AB - In this study, the removal of natural organic matter (NOM) using coconut fiber (CF) and palm oil fiber (POF) was investigated. Preliminary analysis was performed using a jar test for the selection of optimal medium before the fabricated column model experiment. The equilibrium studies on isotherms and kinetic models for NOM adsorption were analyzed using linearized correlation coefficient. Results showed that the equilibrium data were fitted to Langmuir isotherm model for both CF and POF. The most suitable adsorption model was the pseudo-first-order kinetic model for POF and pseudo-second-order kinetic model for CF. The adsorption capacities achieved by the CF and POF were 15.67 and 30.8 mg/g respectively. Based on this investigation, it can be concluded that the POF is the most suitable material for the removal of NOM in semi polluted river water. PMID- 26803101 TI - Assessment of the Heavy Metals in Al Asfar Lake, Al-Hassa, Saudi Arabia. AB - Al Asfar Lake is a shallow wetland and habitat for wildlife and birds in a desert environment. The water of this lake is originated from the drainage water collected by earthen drainage network and discharged into the lake. The purpose of this study was to assess physico- chemical characteristics and some of heavy metals in Al Asfar lake water. The studied parameters are iron, manganese, copper, zinc, cadmium, chromium, lead, pH, electrical conductivity, and nitrate. Forty-five surface water samples were collected in March 2013. The results revealed that the pH ranged from 7.33 to 8.67, electrical conductivity ranged from 8.28 to 11.34 dS/m, and NO(3)(-) ranged from 0.84 to 2.29 mg/L. In addition, heavy metals concentrations in water were found in the following order: Fe > Mn > Cu > Zn > Cd > Cr = Pb. The mean concentrations of heavy metals in surface water of Al Asfar lake ranged from 0.027 to 0.159 ppm, 0.007 to 0.142 ppm, 0.005 to 0.017 ppm, 0.005 to 0.066 ppm, 0.001 to 0.033 ppm, 0 ppm, and 0 ppm for iron, manganese, copper, zinc, cadmium, chromium, and lead, respectively. Moreover, pH, NO(3)(-), Fe, Mn, and Zn concentrations in the surface water of Al Asfar Lake were found to be within the international permissible limits. On the other hand, Cu and Cd concentrations exceeded the international permissible limits. The high level of some parameters of the measured heavy metals could be attributed to the contamination of Al Asfar Lake with discharge water enriched with chemical fertilizers in addition to domestic and industrial effluents. PMID- 26803102 TI - The Impact of Oxone on Disintegration and Dewaterability of Waste Activated Sludge. AB - Biochemical parameters such as soluble chemical oxygen demand (SCOD), phosphate, ammonium nitrogen and proteins are often used to characterize the efficiency of disintegration of waste activated sludge (WAS) flocs and microorganism cells. In this study, the chemical disintegration using peroxymonosulfate (MPS, Oxone) and thermally activated MPS, were evaluated for the destruction of WAS. Our study was conducted for chemical disintegration of WAS by MPS in doses between 84.7 - 847.5 mg/g(TS) activated by temperatures of 50, 70 and 90 degrees C over 30 minutes. The application of these methods causes an increase in the soluble COD value and protein concentration in the supernatant. Also, they positively influence the sludge volume index (SVI) which decreased from 89.8 to 17.2 ml/g. Our research work confirmed that the application of thermally activated MPS may become a new effective way of improving sewage treatment and sewage sludge processing. PMID- 26803103 TI - Influence of SRT and HRT on Bioprocess Performance in Anaerobic Membrane Bioreactors Treating Municipal Wastewater. AB - This study investigated the impact of Solid Retention Time (SRT) (40 to 100 days) and Hydraulic Retention Time (HRT) (2.5 to 8.5 hours) on the treatment of municipal wastewater in pilot and bench scale AnMBRs. The results revealed good permeate quality with respect to concentrations of COD (<40 mg/L) and BOD5 (<10 mg/L) was achieved under all conditions. Over the range of values tested SRT and HRTdid not significantly influence COD and BOD5 removal efficiencies. Extended SRTs resulted in reduced sludge production and enhanced methane production. Oversaturation of dissolved methane in permeate appears to have been responsible for a consistent lack of COD mass balance closure in all tests. After calibration of biokinetic coefficients, PetWin 4 (EnviroSim Canada) was found to effectively simulate the concentrations of particulate COD, readily biodegradable COD and acetic acid over a range of SRTs and HRTs. The calibrated saturation coefficients for hydrolysis and aceticlastic methanogenesis processes were comparable to those reported in literature. The saturation coefficient of fermentation was significantly lower than those reported in literature. The simulated methane mass flows were consistently higher than the measured values which was consistent with the lack of COD mass balance closure and was attributed to reduction of sulfate and oversaturation of the permeate with respect to Henry's Law. PMID- 26803104 TI - Use of a Real Time PCR Assay to Assess the Effect of Pulsed Light Inactivation on Bacterial Cell Membranes and Associated Cell Viability. AB - Research into more rapid and effective means of disinfecting water has become necessary due to the recognition that not all pathogenic species are being removed by chemical means. There is an extent of research highlighting the benefits of pulsed light for the disinfection of water. This study aims to determine the ability of a real time polymerase chain reaction assay to evaluate microbial inactivation of pulsed light treated cells. Findings show that pulsed light is a more rapid means of inactivating test species than standard UV lamp systems. A linear relationship between cell number and polymerase chain reaction amplification was obtained. A difference in threshold value (Ct) of approximately 4 (p <= 0.05) was obtained for DNA amplification following the addition of the dye for pulsed ultrviolet (PUV)-treated Bacillus cells. Membrane protein leakage proved an effective means of determining membrane damage for both Bacillus and E. coli test species following PUV treatment. This membrane damage was not evident for cells exposed to low pressure ultraviolet (LPUV). Findings describe suggest that PUV treatment induced a viable but nonculturable state in treated cells. PMID- 26803105 TI - Approach to Assessing the Effects of Aerial Deposition on Water Quality in the Alberta Oil Sands Region. AB - Snow cover forms a porous medium that acts as a receptor for aerially deposited polycyclic aromatic hydrocarbons (PAHs) and metals. The snowpack, acting as a temporary storage reservoir, releases contaminants accumulating over the winter during a relatively short melt period. This process could result in elevated concentrations of contaminants in melt water. Recent studies in the Alberta oil sands region have documented increases in snowpack and lake sediment concentrations; however, no studies have addressed the fate and transport of contaminants during the snowmelt period. This study describes modelling approaches that were developed to assess potential effects of aerially deposited PAHs and metals to snowpack and snowmelt water concentrations. The contribution of snowmelt to freshwater PAH concentrations is assessed using a dynamic, multi compartmental fate model, and the contribution to metal concentrations is estimated using a mass-balance approach. The modelling approaches described herein were applied to two watersheds in the Alberta oil sands region for two planned oil sands developments. Accumulation of PAHs in a lake within the deposition zone was also modelled for comparison to observed concentrations. PMID- 26803106 TI - Sirtuin 6 modulates hypoxia-induced autophagy in nasal polyp fibroblasts via inhibition of glycolysis. AB - BACKGROUND: To elucidate the interaction between hypoxia-induced autophagy and glycolysis in nasal polyp fibroblasts, and the regulatory role of Sirtuin 6 (SIRT6) in the pathogenesis of nasal polyp. OBJECTIVE: Through examining the expressions of lactate dehydrogenase (LDH), microtubule-associated protein II light chain 3 (LC3II) (an autophagy marker), and production of lactate under hypoxia, the interaction between autophagy and glycolysis was investigated. The role of SIRT6 on the hypoxia-induced autophagy and glycolysis was also examined. METHODS: Nasal polyp specimens were used to examine the expressions of hypoxia inducible factor (HIF) 1alpha, LDH, and LC3II by Western blot analysis, and primary cultures of nasal polyp fibroblasts were established from resected nasal polyps to measure hypoxia-induced LDH and LC3II expression by Western blot analysis and lactate production by colorimetry. Forced expression of SIRT6 with a lentiviral-based technique was used to evaluate its suppressive effect on autophagy and glycolysis. Immunohistochemical staining was performed to detect the expressions of SIRT6, LDH, and beclin (another autophagy marker) in nasal polyps. RESULTS: Expression of HIF-1alpha, LDH, and an autophagy marker, LC3II, are increased in nasal polyp specimens, and forced expression of SIRT6 in nasal polyp fibroblasts inhibited LDH expression, lactate production under hypoxia, and SIRT6. An immunohistochemistry study of nasal polyp showed that SIRT6 expression was reduced and LDH and beclin were enhanced. CONCLUSION: Analysis of these data indicated that hypoxia may contribute to the formation of nasal polyp by promoting autophagy in nasal polyp fibroblasts. Through the antiglycolytic activity of SIRT6, the autophagy was suppressed, which was beneficial to nasal polyp formation. Modulation of glucose metabolism through SIRT6-based strategy may possess therapeutic potential for nasal polyposis in the future. PMID- 26803150 TI - Effect of Electronic Cigarette Use on the Urge-to-Cough Sensation. AB - INTRODUCTION: Electronic cigarettes (e-cigs) have attained common usage worldwide, yet knowledge of their physiological effects remains minimal. The aim of this study was to evaluate the effect of a single exposure to e-cig vapor on the urge-to-cough (UTC) threshold and C5. METHODS: Seventeen healthy nonsmokers underwent C5 measurement employing capsaicin cough challenge at baseline, 15 minutes, and 24 hours after e-cig exposure (30 puffs 30 seconds apart). The endpoint of cough challenge is C5, the concentration of capsaicin inducing five or more coughs. The UTC threshold (Cu) is defined as the lowest concentration of capsaicin inducing UTC without an associated motor cough. RESULTS: The Cu and C5 were significantly inhibited (Cu and C5 increased) 15 minutes after e-cig use. Mean log Cu rose from -0.035+/-0.08 (SEM) to 0.21+/-0.12 (P = .005). Mean log C5 increased from 0.60+/-0.11 to 0.92+/-0.16 (P = .001). By 24 hours after e-cig exposure, Cu and C5 had returned to baseline levels. CONCLUSIONS: A single session of e-cig use, approximating nicotine exposure of one tobacco cigarette, induces significant inhibition of the Cu, as well as C5. Previous studies implicate nicotine as the agent responsible for suppression of C5, and we hypothesize a similar role for nicotine in the suppression of the Cu. Given our observation of the effect of a single e-cig exposure, studies of the respiratory physiologic implications of repeated or chronic e-cig use are warranted. IMPLICATIONS: This is the first study to demonstrate that a single exposure to an e-cig significantly inhibits the Cu as measured by capsaicin cough challenge testing. These findings add to the growing body of evidence that e-cig vapor is not a physiologically benign substance, and support further investigation of the effects of repeated or chronic use of e-cigs on cough sensitivity and other respiratory parameters. PMID- 26803151 TI - Ominous or innocent? PMID- 26803152 TI - Response to "Is denosumab a long-term option for the treatment of parathyroid carcinoma?". PMID- 26803153 TI - Clostridium septicum arthritis and aortitis in a patient with underlying colon cancer. PMID- 26803154 TI - Is denosumab a long-term option for the treatment of parathyroid carcinoma? PMID- 26803155 TI - MuCor: mutation aggregation and correlation. AB - MOTIVATION: There are many tools for variant calling and effect prediction, but little to tie together large sample groups. Aggregating, sorting and summarizing variants and effects across a cohort is often done with ad hoc scripts that must be re-written for every new project. In response, we have written MuCor, a tool to gather variants from a variety of input formats (including multiple files per sample), perform database lookups and frequency calculations, and write many types of reports. In addition to use in large studies with numerous samples, MuCor can also be employed to directly compare variant calls from the same sample across two or more platforms, parameters or pipelines. A companion utility, DepthGauge, measures coverage at regions of interest to increase confidence in calls. AVAILABILITY AND IMPLEMENTATION: Source code is freely available at https://github.com/blachlylab/mucor and a Docker image is available at https://hub.docker.com/r/blachlylab/mucor/ CONTACT: james.blachly@osumc.eduSupplementary data: Supplementary data are available at Bioinformatics online. PMID- 26803156 TI - Quantitative trait association study for mean telomere length in the South Asian genomes. AB - MOTIVATION: Mean telomere length (MTL) is associated with cancers and age-related diseases, which necessitates identification of genomic and environmental factors that impact telomere length dynamics. Here, we present a pilot genome wide association (GWA) study for MTL in South Asian population using publicly available next generation whole genome sequences (WGS), both for MTL and genotype calculations. RESULTS: MTL in the studied population was not correlated with age, which is in accordance with previous reports. Further, we identified that individuals with Sikh religion had longer telomeres, which may be the result of complex interaction between genetic background and environmental factors. Finally, we identified 51 MTL-associated SNPs residing in five loci. The top ones were located in ADARB2 gene, which has previously been implicated with extreme old age. CONCLUSION: Our results show that WGS data can be used in telomere length studies. In addition, we introduce novel loci implicated in MTL that may be worth considering in further telomere studies. CONTACT: aarakelyan@sci.am SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26803157 TI - lodGWAS: a software package for genome-wide association analysis of biomarkers with a limit of detection. AB - Genome-wide association study (GWAS) of a biomarker is complicated when the assay procedure of the biomarker is restricted by a Limit of Detection (LOD). Those observations falling outside the LOD cannot be simply discarded, but should be included into the analysis by applying an appropriate statistical method. However, the problem of LOD in GWAS analysis of such biomarkers is usually overlooked. 'lodGWAS' is a flexible, easy-to-use R package that provides a simple and elegant way for GWAS analysis of such biomarkers while simultaneously accommodating the problem of LOD by applying a parametric survival analysis method. AVAILABILITY AND IMPLEMENTATION: http://cran.r project.org/web/packages/lodGWAS CONTACTS: a.vaez@umcg.nl or i.m.nolte@umcg.nl SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26803158 TI - FamAgg: an R package to evaluate familial aggregation of traits in large pedigrees. AB - Familial aggregation analysis is the first fundamental step to perform when assessing the extent of genetic background of a disease. However, there is a lack of software to analyze the familial clustering of complex phenotypes in very large pedigrees. Such pedigrees can be utilized to calculate measures that express trait aggregation on both the family and individual level, providing valuable directions in choosing families for detailed follow-up studies. We developed FamAgg, an open source R package that contains both established and novel methods to investigate familial aggregation of traits in large pedigrees. We demonstrate its use and interpretation by analyzing a publicly available cancer dataset with more than 20 000 participants distributed across approximately 400 families. AVAILABILITY AND IMPLEMENTATION: The FamAgg package is freely available at the Bioconductor repository, http://www.bioconductor.org/packages/FamAgg CONTACT: Christian.Weichenberger@eurac.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26803159 TI - ParDRe: faster parallel duplicated reads removal tool for sequencing studies. AB - Current next generation sequencing technologies often generate duplicated or near duplicated reads that (depending on the application scenario) do not provide any interesting biological information but can increase memory requirements and computational time of downstream analysis. In this work we present ParDRe, a de novo parallel tool to remove duplicated and near-duplicated reads through the clustering of Single-End or Paired-End sequences from fasta or fastq files. It uses a novel bitwise approach to compare the suffixes of DNA strings and employs hybrid MPI/multithreading to reduce runtime on multicore systems. We show that ParDRe is up to 27.29 times faster than Fulcrum (a representative state-of-the art tool) on a platform with two 8-core Sandy-Bridge processors. AVAILABILITY AND IMPLEMENTATION: Source code in C ++ and MPI running on Linux systems as well as a reference manual are available at https://sourceforge.net/projects/pardre/ CONTACT: jgonzalezd@udc.es. PMID- 26803160 TI - Alloscore: a method for predicting allosteric ligand-protein interactions. AB - Allosteric ligands have increasingly gained attention as potential therapeutic agents due to their higher target selectivity and lower toxicity compared with classic orthosteric ligands. Despite the great interest in the development of allosteric drugs as a new tactic in drug discovery, the understanding of the ligand-protein interactions underlying allosteric binding represents a key challenge. Herein, we introduce Alloscore, a web server that predicts the binding affinities of allosteric ligand-protein interactions. This method exhibits prominent performance in describing allosteric binding and could be useful in allosteric virtual screening and the structural optimization of allosteric agonists/antagonists. AVAILABILITY AND IMPLEMENTATION: The Alloscore server and tutorials are freely available at http://mdl.shsmu.edu.cn/alloscore CONTACT: jian.zhang@sjtu.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26803161 TI - PAA: an R/bioconductor package for biomarker discovery with protein microarrays. AB - The R/Bioconductor package Protein Array Analyzer (PAA) facilitates a flexible analysis of protein microarrays for biomarker discovery (esp., ProtoArrays). It provides a complete data analysis workflow including preprocessing and quality control, uni- and multivariate feature selection as well as several different plots and results tables to outline and evaluate the analysis results. As a main feature, PAA's multivariate feature selection methods are based on recursive feature elimination (e.g. SVM-recursive feature elimination, SVM-RFE) with stability ensuring strategies such as ensemble feature selection. This enables PAA to detect stable and reliable biomarker candidate panels. AVAILABILITY AND IMPLEMENTATION: PAA is freely available (BSD 3-clause license) from http://www.bioconductor.org/packages/PAA/ CONTACT: michael.turewicz@rub.de or martin.eisenacher@rub.de. PMID- 26803162 TI - DesignSignatures: a tool for designing primers that yields amplicons with distinct signatures. AB - For numerous experimental applications, PCR primers must be designed to efficiently amplify a set of homologous DNA sequences while giving rise to amplicons with maximally diverse signatures. We developed DesignSignatures to automate the process of designing primers for high-resolution melting (HRM), fragment length polymorphism (FLP) and sequencing experiments. The program also finds the best restriction enzyme to further diversify HRM or FLP signatures. This enables efficient comparison across many experimental designs in order to maximize signature diversity. AVAILABILITY AND IMPLEMENTATION: DesignSignatures is accessible as a web tool at www.DECIPHER.cee.wisc.edu, or as part of the DECIPHER open source software package for R available from BioConductor. CONTACT: kalin@discovery.wisc.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26803163 TI - BISQUE: locus- and variant-specific conversion of genomic, transcriptomic and proteomic database identifiers. AB - Biological sequence databases are integral to efforts to characterize and understand biological molecules and share biological data. However, when analyzing these data, scientists are often left holding disparate biological currency-molecular identifiers from different databases. For downstream applications that require converting the identifiers themselves, there are many resources available, but analyzing associated loci and variants can be cumbersome if data is not given in a form amenable to particular analyses. Here we present BISQUE, a web server and customizable command-line tool for converting molecular identifiers and their contained loci and variants between different database conventions. BISQUE uses a graph traversal algorithm to generalize the conversion process for residues in the human genome, genes, transcripts and proteins, allowing for conversion across classes of molecules and in all directions through an intuitive web interface and a URL-based web service. AVAILABILITY AND IMPLEMENTATION: BISQUE is freely available via the web using any major web browser (http://bisque.yulab.org/). Source code is available in a public GitHub repository (https://github.com/hyulab/BISQUE). CONTACT: haiyuan.yu@cornell.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26803164 TI - Computational approaches to define a human milk metaglycome. AB - MOTIVATION: The goal of deciphering the human glycome has been hindered by the lack of high-throughput sequencing methods for glycans. Although mass spectrometry (MS) is a key technology in glycan sequencing, MS alone provides limited information about the identification of monosaccharide constituents, their anomericity and their linkages. These features of individual, purified glycans can be partly identified using well-defined glycan-binding proteins, such as lectins and antibodies that recognize specific determinants within glycan structures. RESULTS: We present a novel computational approach to automate the sequencing of glycans using metadata-assisted glycan sequencing, which combines MS analyses with glycan structural information from glycan microarray technology. Success in this approach was aided by the generation of a 'virtual glycome' to represent all potential glycan structures that might exist within a metaglycomes based on a set of biosynthetic assumptions using known structural information. We exploited this approach to deduce the structures of soluble glycans within the human milk glycome by matching predicted structures based on experimental data against the virtual glycome. This represents the first meta-glycome to be defined using this method and we provide a publically available web-based application to aid in sequencing milk glycans. AVAILABILITY AND IMPLEMENTATION: http://glycomeseq.emory.edu CONTACT: sagravat@bidmc.harvard.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26803165 TI - cAMP-Dependent Calcium Oscillations of Astrocytes: An Implication for Pathology. AB - Astrocytes in various brain regions exhibit spontaneous intracellular calcium elevations both in vitro and in vivo; however, neither the temporal pattern underlying this activity nor its function has been fully evaluated. Here, we utilized a long-term optical imaging technique to analyze the calcium activity of more than 4000 astrocytes in acute hippocampal slices as well as in the neocortex and hippocampus of head-restrained mice. Although astrocytic calcium activity was largely sparse and irregular, we observed a subset of cells in which the fluctuating calcium oscillations repeated at a regular interval of ~30 s. These intermittent oscillations i) depended on type 2 inositol 1,4,5-trisphosphate receptors; ii) consisted of a complex reverberatory interaction between the soma and processes of individual astrocytes; iii) did not synchronize with those of other astrocytes; iv) did not require neuronal firing; v) were modulated through cAMP-protein kinase A signaling; vi) were facilitated under pathological conditions, such as energy deprivation and epileptiform hyperexcitation; and vii) were associated with enhanced hypertrophy in astrocytic processes, an early hallmark of reactive gliosis, which is observed in ischemia and epilepsy. Therefore, calcium oscillations appear to be associated with a pathological state in astrocytes. PMID- 26803167 TI - Regulation of Cognitive Processing by Hippocampal Cholinergic Tone. AB - Cholinergic dysfunction has been associated with cognitive abnormalities in a variety of neurodegenerative and neuropsychiatric diseases. Here we tested how information processing is regulated by cholinergic tone in genetically modified mice targeting the vesicular acetylcholine transporter (VAChT), a protein required for acetylcholine release. We measured long-term potentiation of Schaffer collateral-CA1 synapses in vivo and assessed information processing by using a mouse touchscreen version of paired associates learning task (PAL). Acquisition of information in the mouse PAL task correlated to levels of hippocampal VAChT, suggesting a critical role for cholinergic tone. Accordingly, synaptic plasticity in the hippocampus in vivo was disturbed, but not completely abolished, by decreased hippocampal cholinergic signaling. Disrupted forebrain cholinergic signaling also affected working memory, a result reproduced by selectively decreasing VAChT in the hippocampus. In contrast, spatial memory was relatively preserved, whereas reversal spatial memory was sensitive to decreased hippocampal cholinergic signaling. This work provides a refined roadmap of how synaptically secreted acetylcholine influences distinct behaviors and suggests that distinct forms of cognitive processing may be regulated in different ways by cholinergic activity. PMID- 26803166 TI - Monaural Congenital Deafness Affects Aural Dominance and Degrades Binaural Processing. AB - Cortical development extensively depends on sensory experience. Effects of congenital monaural and binaural deafness on cortical aural dominance and representation of binaural cues were investigated in the present study. We used an animal model that precisely mimics the clinical scenario of unilateral cochlear implantation in an individual with single-sided congenital deafness. Multiunit responses in cortical field A1 to cochlear implant stimulation were studied in normal-hearing cats, bilaterally congenitally deaf cats (CDCs), and unilaterally deaf cats (uCDCs). Binaural deafness reduced cortical responsiveness and decreased response thresholds and dynamic range. In contrast to CDCs, in uCDCs, cortical responsiveness was not reduced, but hemispheric-specific reorganization of aural dominance and binaural interactions were observed. Deafness led to a substantial drop in binaural facilitation in CDCs and uCDCs, demonstrating the inevitable role of experience for a binaural benefit. Sensitivity to interaural time differences was more reduced in uCDCs than in CDCs, particularly at the hemisphere ipsilateral to the hearing ear. Compared with binaural deafness, unilateral hearing prevented nonspecific reduction in cortical responsiveness, but extensively reorganized aural dominance and binaural responses. The deaf ear remained coupled with the cortex in uCDCs, demonstrating a significant difference to deprivation amblyopia in the visual system. PMID- 26803168 TI - Responding to refusal of recommended cesarean section: Promoting good parenting. AB - Consideration of what a "good parent" would do in controversial perinatal cases has been largely absent from to ethics literature. This article argues when a cesarean section is required to prevent death or serious disability for a fetus, the pregnant woman has an ethical (although not legal) obligation to undergo that procedure even when she has concerns or conflicting commitments. Further, a clinician may be justified in using persuasive counseling when there is grave harm at stake that the patient has a moral obligation to prevent. This conclusion is tested by exploring its implications in several other analogous controversial contexts. PMID- 26803169 TI - Selenium supplementation has beneficial and detrimental effects on immunity to influenza vaccine in older adults. AB - BACKGROUND & AIMS: Mortality resulting from influenza (flu) virus infections occurs primarily in the elderly through declining immunity. Studies in mice have suggested beneficial effects of selenium (Se) supplementation on immunity to flu but similar evidence is lacking in humans. A dietary intervention study was therefore designed to test the effects of Se-supplementation on a variety of parameters of anti-flu immunity in healthy subjects aged 50-64 years. METHODS: A 12-week randomized, double-blinded, placebo-controlled clinical trial (ClinicalTrials.govNCT00279812) was undertaken in six groups of individuals with plasma Se levels <110 ng/mL. Four groups were given daily capsules of yeast enriched with 0 MUg Se/day (SeY-0/d; n = 20), 50 MUg Se/d (SeY-50/d; n = 18), 100 MUg Se/d (SeY-100/d; n = 21) or 200 MUg Se/d (SeY-200/d; n = 23). Two groups were given onion-containing meals with either <1 MUg Se/d (SeO-0/d; n = 17) or 50 MUg Se/d (SeO-50/d; n = 18). Flu vaccine was administrated at week 10 and immune parameters were assessed until week 12. RESULTS: Primary study endpoints were changes in cellular and humoral immune responses. Supplementation with SeY and SeO affected different aspects of cellular immunity. SeY increased Tctx-ADCC cell counts in blood (214%, SeY-100/d) before flu vaccination and a dose-dependent increase in T cell proliferation (500%, SeY-50/100/200/d), IL-8 (169%, SeY-100/d) and IL-10 (317%, SeY-200/d) secretion after in vivo flu challenge. Positive effects were contrasted by lower granzyme B content of CD8 cells (55%, SeY 200/d). SeO (Se 50 MUg/d) also enhanced T cell proliferation after vaccination (650%), IFN-gamma (289%), and IL-8 secretion (139%), granzyme (209%) and perforin (190%) content of CD8 cells but inhibited TNF-alpha synthesis (42%). Onion on its own reduced the number of NKT cells in blood (38%). These effects were determined by comparison to group-specific baseline yeast or onion control groups. Mucosal flu-specific antibody responses were unaffected by Se-supplementation. CONCLUSION: Se-supplementation in healthy human adults with marginal Se status resulted in both beneficial and detrimental effects on cellular immunity to flu that was affected by the form of Se, supplemental dose and delivery matrix. These observations call for a thorough evaluation of the risks and benefits associated with Se-supplementation. PMID- 26803171 TI - Cross-sectional and longitudinal associations between sleep and health-related quality of life in pregnant women: A prospective observational study. AB - BACKGROUND: Sleep disturbances are common in women, especially during pregnancy. Previous studies have confirmed the importance of sleep disturbances as a risk factor of adverse pregnancy outcomes and the need for screening and treatment of inadequate sleep. These reports, however, did not examine health-related quality of life which may be affected by sleep long before adverse clinical consequences are detectable in women during pregnancy. OBJECTIVES: To examine the cross sectional and longitudinal association between sleep and health-related quality of life in pregnant women. DESIGN: A prospective observational study. SETTING: A university-affiliated hospital in Taiwan and participants' homes. PARTICIPANTS: A total of 164 pregnant women completed questionnaires and wore a wrist actigraphy monitor for 7 days each trimester. METHODS: Objective sleep was measured by actigraphy, subjective sleep was measured by the Pittsburgh Sleep Quality Index, and health-related quality of life was measured using the SF-12v2 questionnaire across three trimesters. Multiple linear regression analyses were performed to evaluate the cross-sectional and longitudinal associations between sleep and health-related quality of life. RESULTS: Sixty-four (39.0%) women consistently had an average sleep efficiency<85% by actigraphy and 40 (24.4%) had a Pittsburgh Sleep Quality Index global score>5 in all three trimesters. Cross-sectionally, more actigraphic daytime sleep (p=0.04) and better subjective sleep quality (p<0.01) were associated with better physical health-related quality of life in first-trimester pregnant women. Better actigraphic sleep efficiency (p=0.04) and better subjective sleep quality (p<0.01) were associated with better mental health-related quality of life in second-trimester pregnant women. Longer actigraphic total nighttime sleep (p<0.01) and better subjective sleep quality (p<0.01) were associated with better mental health-related quality of life in third-trimester pregnant women. Longitudinally, first-trimester actigraphic total nighttime sleep (p<0.05) and subjective sleep quality (p<0.01) predicted mental health-related quality of life in the second and third trimester. CONCLUSIONS: Sleep disturbances are a highly prevalent and persistent problem in pregnant women. Adequate sleep is essential for women at all pregnancy stages and improving nocturnal sleep quantity and quality in early gestation is of utmost importance for an optimal health-related quality of life later in pregnancy. PMID- 26803170 TI - Validation of ventilator-derived VCO2 measurements to determine energy expenditure in ventilated critically ill children. AB - BACKGROUND & AIMS: Indirect calorimetry (IC) is considered the gold standard to determine resting energy expenditure (REE) but its availability in PICUs worldwide is limited. Ventilator-derived VCO2 could potentially improve the possibility of performing REE measurements. We investigated whether ventilator derived VCO2 values are comparable to IC-derived VCO2 values and can clinically be used in clinical practice to determine REE. METHODS: VCO2-values were simultaneously collected in mechanically ventilated children from IC (Deltatrac(r)) and Servo-I(r) ventilator on a minute base over at least 10 min period of steady state. REE was calculated using the modified Weir formula (for IC) or REE = 5.5*VCO2 (L/min)*1440 (for the Servo-I values) and compared with frequently used predictive equations by Schofield and the WHO to calculate REE. RESULTS: Measurements were performed in 41 children; median age 2 years. The mean relative difference between VCO2 measured by IC and Servo-I(r) was 15.6% (p = 0.002), and limits of agreement in the Bland-Altman analysis were wide. Comparable measurements, defined as a difference <=10% between IC and Servo-I(r) VCO2 values, were seen in 18 (44%) children, but this proportion was 70% in children >=15 kg. In this group, REE could be accurately predicted using Servo I(r) derived VCO2 values and this method was superior to the use of predictive equations. The Servo-I(r) derived VCO2 values were not sufficiently accurate for the large proportion of children weighing <15 kg. CONCLUSIONS: In children >=15 kg, VCO2 measurements of the Servo-I(r) seem sufficiently accurate for use in clinical practice and may be used to determine energy expenditure in the future. PMID- 26803172 TI - Workplace violence against nurses--prevalence and association with hospital organizational characteristics and health-promotion efforts: Cross-sectional study. AB - PURPOSE/OBJECTIVES: To determine the prevalence of workplace violence and explore the role of hospital organizational characteristics and health promotion efforts in reducing hospital violence among nurses in Taiwan. DESIGN: Cross-sectional survey. SETTING: One hundred hospitals across Taiwan. SAMPLE: The final sample in our study comprised responses from 26,979 nurses. METHODS: The data were obtained from a nationwide hospital survey, Physical and Mental Health and Safety Needs in Full-Time Health Care Staff, which was developed and conducted by the Bureau of Health Promotion, Taiwan, in 2011. MAIN RESEARCH VARIABLES: The main dependent variable was whether nurses had experienced violence within the past year. Physical violence, threatened or intimidated personal safety, verbal violence or sexual harassment were all included. FINDINGS: Of the 26,979 nurses, 13,392 nurses (49.6%) had experienced at least one episode of any type of violence in the past year; 5150 nurses (19.1%) had been exposed to physical violence, and 12,491 nurses (46.3%) had been exposed to non-physical violence. The prevalence of having experienced any violence varied widely and ranged from the highest (55.5%) in an emergency room or intensive care unit to the lowest (28.3%) among those aged 55-65 years. After adjusting for other characteristics, younger nurses were significantly more likely to be exposed to any violent threat. Nurses working in public hospitals had a significantly higher risk of workplace violence than those working in private hospitals. Significant variations were also observed among work units. Although nurses working in a certified health promoting hospital (HPH) did not have a lower risk of workplace violence, those working in an outstanding HPH had a significantly lower risk of workplace violence. A similar pattern was observed for non-physical violence. CONCLUSIONS: Workplace violence is a major challenge to workplace safety for nurses in hospitals. This large scale nurse survey identified individual, work and hospital characteristics associated with workplace violence among hospital nurses. Preventive efforts in reducing hospital violence shall be targeted these high risk groups and settings. IMPLICATIONS FOR NURSING: This nationwide nurse survey assisted us in more clearly understanding the scope of the hospital violence facing nurses and identifying critical risk factors. The findings not only identified the most common locations of violence in hospitals but also suggested that extensive investments and efforts by hospitals in health promotion are crucial. PMID- 26803173 TI - Accuracy in the digital workflow: From data acquisition to the digitally milled cast. AB - STATEMENT OF PROBLEM: The accuracy of digital impressions and the milling of implant crowns greatly influence the clinical outcome of implant restorations. PURPOSE: The purpose of this in vitro study was to calculate the propagation of error in the process of milling an implant crown. MATERIAL AND METHODS: Thirty digitally milled casts made directly from a reference model were prepared. The casts were scanned with a laboratory scanner, and 30 standard tesselation language (STL) datasets from each group were imported to inspection software. In each analysis, STL datasets were aligned by a repeated best fit algorithm, and 18 specified contact locations of interest were measured in mean volumetric deviations. The master reference dataset was aligned 30 times to the master reference dataset to determine the software variation. The reference datasets were aligned to the master reference dataset to determine the scanner variation. The milled cast datasets were aligned to the master reference dataset to determine the milling variation. The 18 specified contact locations of interest were pooled by cusps, occlusal ridge/fossae, interproximal contacts, facial/lingual aspect, and implant position. The pooled areas were statistically analyzed by comparing each group with the reference model to investigate the mean volumetric deviations accounting for accuracy and standard deviations for precision. RESULTS: Software and scanner variation were negligible. Variations in the milled models resulting from software and scanner error exhibited statistical significance (P<.001). Software, scanner, and milling error were shown to propagate through the digital workflow to the milled model. CONCLUSIONS: The pooled locations may describe the reliability of the milling process as it applies to specific anatomic locations on the tooth. PMID- 26803175 TI - Effects of build direction on the mechanical properties of 3D-printed complete coverage interim dental restorations. AB - STATEMENT OF PROBLEM: The application of 3-dimensional printing technology is emerging in dentistry and is being increasingly used to fabricate dental restorations. To date, scientific evidence is lacking regarding the effect of different factors on the mechanical properties of the printed restorations with the additive manufacturing technique. PURPOSE: The purpose of this in vitro study was to evaluate the effect of build direction (layer orientation) on the mechanical properties of a novel 3-dimensionally (3D)-printed dental restorative material. MATERIAL AND METHODS: Based on the printing direction, 2 groups were tested. In the first group (n=20), the specimens were vertically printed with the layers oriented perpendicular to the load direction. In the second group (n=20), the specimens were horizontally printed with the layers oriented parallel to the load direction. All specimens were fabricated using the DW028D 3D-printer. The specimens were loaded with a universal testing machine at a crosshead speed of 1 mm/min with a 10-kN load cell. The test was performed at room temperature (22 degrees C) under dry testing conditions. The compressive strength was calculated for both groups, and the results were compared using the unpaired t test (alpha=.05). RESULTS: The mean +/-SD compressive strength for the vertically printed specimens was 297 MPa (+/-34) compared with 257 MPa (+/-41) for the horizontally printed specimens (P=.002). CONCLUSIONS: Within the limitations of this study, the layer orientation was found to influence the compressive strength of the material. Vertically printed specimens with the layers oriented perpendicular to load direction have improved mechanical properties more than horizontally printed specimens with the layers oriented parallel to load direction. PMID- 26803174 TI - Combining digital photography with cylinder-type magnets to record the screw access hole in a cement-retained implant prosthesis. PMID- 26803176 TI - Atraumatic surgical extrusion to improve tooth restorability: A clinical report. AB - This clinical report describes the use of an "atraumatic" vertical extraction system to facilitate the restorative treatment of a tooth that would otherwise be considered unrestorable because of subgingival caries. Minimally invasive surgical root extrusion was undertaken using the Benex extraction system, which can provide controlled tooth extrusion with minimal deformation of the bone socket. A carious endodontically treated mandibular premolar was extruded to provide routine restorative treatment and endodontic retreatment. PMID- 26803177 TI - Effect of implant insertion and loading protocol on long-term stability and crestal bone loss: A comparative study. AB - STATEMENT OF PROBLEM: Different insertion and loading protocols have been used to implement implant therapy; the consequences of these methods are unclear. PURPOSE: The purpose of this retrospective study was to compare the long-term outcomes of different implant insertion and loading protocols on crestal bone loss. MATERIAL AND METHODS: This was a nonrandomized retrospective study investigating data of patients in a private practice. Data were collected by an independent Tel Aviv University group from the patient records of a general practitioner's private practice. A total of 1688 implants were inserted in 343 patients whose records met the inclusion criteria, that is, 1317 immediately placed implants (IP group), 310 early placed implants (EP group) placed 6 to 8 weeks after implant placement, and 61 delayed placement implants (DP group) placed 4 to 6 months after extraction. The groups were also divided by implant loading method, giving 1203 immediately loaded implants (IL group), 273 early loaded implants (EL group) loaded within 4 to 10 weeks after implant placement, and 212 delayed loading implants (DL group) loaded within 3 to 6 months. Mixed model analysis was used to account for the different number of implants for each patient. RESULTS: The average follow-up time was 107 months, with a cumulative implant survival rate of 95.6% and an average crestal bone loss of 2.03 mm. No statistical differences (P>.05) were found among the insertion or loading protocols. However, additional statistical analysis showed the influence of implant type on marginal bone loss (P<.05). CONCLUSIONS: The 3-implant insertion and loading protocols exhibited minimal crestal bone loss and a high survival rate. PMID- 26803178 TI - Oral cancer or periimplantitis: A clinical dilemma. AB - The purpose of this article was to draw attention to a periimplantitis-like clinical presentation of oral malignancy around dental implants, a phenomenon that may develop without any associated risk factors for oral cancer. Such a benign appearance of oral malignancy may lead to delay in the diagnosis and initiation of ensuing treatment. Therefore, chronic nonhealing inflammatory lesions around dental implants should be considered as highly suspicious. PMID- 26803179 TI - Prevalence of alterations in the characteristics of smile symmetry in an adult population from southern Europe. AB - STATEMENT OF PROBLEM: Deviation from the facial midline and inclination of the dental midline or occlusal plane has been described as extremely influential in the layperson's perceptions of the overall esthetics of the smile. PURPOSE: The purpose of this study was to determine the prevalence of deviation from the facial midline and inclination of the dental midline or occlusal plane in a selected sample. MATERIAL AND METHODS: White participants from a European population (N=158; 93 women, 65 men) who met specific inclusion criteria were selected for the present study. Standardized 1:1 scale frontal photographs were made, and 3 variables of all participants were measured: midline deviation, midline inclination, and inclination of the occlusal plane. Software was used to measure midline deviation and inclination, taking the bipupillary line and the facial midline as references. Tests for normality of the sample were explored and descriptive statistics (means +/-SD) were calculated. The chi-square test was used to evaluate differences in midline deviation, midline inclination, and occlusion plane (alpha=.05) RESULTS: Frequencies of midline deviation (>2 mm), midline inclination (>3.5 degrees), and occlusal plane inclination (>2 degrees) were 31.64% (mean 2.7+/-1.23 mm), 10.75% (mean 7.9 degrees +/-3.57), and 25.9% (mean 9.07 degrees +/-3.16), respectively. No statistically significant differences (P>.05) were found between sex and any of the esthetic smile values. CONCLUSIONS: The incidence of alterations with at least 1 altered parameter that affected smile esthetics was 51.9% in a population from southern Europe. PMID- 26803180 TI - Changes in alveolar bone density around immediate functionally and nonfunctionally loaded implants. AB - STATEMENT OF PROBLEM: Few studies compare the radiographic changes in bone density associated with immediate implant loading protocols. PURPOSE: The purpose of this longitudinal study was to quantitatively assess radiographic changes in alveolar bone density around immediate functionally and nonfunctionally loaded implants. MATERIAL AND METHODS: A prospective longitudinal study was conducted in which 20 participants with partially edentulous mandibles received implants that were immediately loaded either functionally (IFL) or nonfunctionally (INFL). Standardized intraoral periapical radiographs were made at baseline, 3, and 6 months. These were digitized and analyzed using the histogram tool of the GNU Image Modulation Program for changes in alveolar bone density at crestal and lateral apical levels around the implant. RESULTS: An increase in the mean lateral apical pixel grayscale values of 4.68 +/-0.80 at 3 months and 4.15 +/ 0.29 at 6 months was observed with IFL, while INFL demonstrated an increase of 5.66 +/-0.53 at 3 months and 6.07 +/-0.59 at 6 months. A decrease in the mean crestal pixel grayscale values of -24.40 +/-7.41 with IFL and -16.86 +/-5.14 with INFL was found from baseline to 3 months. CONCLUSIONS: On the basis of this longitudinal study, it was concluded that immediate loading stimulated alveolar bone formation at 6 months after implant placement. The immediate functional loading of implants resulted in a significantly greater degree of bone demineralization at the alveolar crest from implant placement up to 3 months compared with immediate nonfunctional loading. PMID- 26803181 TI - Aging effect of atmospheric air on lithium disilicate ceramic after nonthermal plasma treatment. AB - STATEMENT OF PROBLEM: Nonthermal plasma (NTP) treatment is an alternative technique for promoting the adhesion of resin cement to lithium disilicate ceramic. However, no study has evaluated whether the surface modifications are affected by atmospheric air aging. PURPOSE: The purposes of this in vitro study were to characterize the lithium disilicate surface after depositing an organosilicon film with NTP treatment and to verify the surface energy before and after atmospheric air aging up to 30 days. MATERIAL AND METHODS: Sixteen lithium disilicate disks (10*3 mm) were prepared, and their surfaces were treated with a mixture of hexamethyldisiloxane and argon, followed by oxygen plasma treatment, both for 30 minutes. The lithium disilicate surface was characterized through scanning electron microscopy, energy-dispersive spectroscopy, and atomic force microscopy. Surface energy analysis was performed before (T0) and immediately after NTP treatment (T1) and after atmospheric air aging for 7 (T2), 15 (T3), and 30 days (T4). Data were submitted to analysis of variance followed by the Tukey HSD test (alpha=.05). RESULTS: Carbon, oxygen, and silicon were identified on the disilicate surface after NTP treatment, suggesting organosilicon film adhesion. Air aging did not modify the film morphology. At T1, the surface energy was significantly higher compared with other periods, and the water contact angle on the disilicate surface was reduced to 0 degrees. Similar surface energy was observed for T0, T2, T3, and T4. CONCLUSIONS: On the basis of the results of this in vitro study, NTP treatment can promote bonding to lithium disilicate surfaces because of its high surface wettability. However, after air aging, the wettability was not durable. PMID- 26803182 TI - The effect of parturition induction treatment on interval to calving, calving ease, postpartum uterine health, and resumption of ovarian cyclicity in beef heifers. AB - The aim of this study was to compare the effects of two parturition induction protocols with a nontreated control group, on interval to calving, calving ease, postpartum uterine health, and ovarian cyclicity in beef heifers. At Day 285 of gestation, 81 crossbred recipient beef heifers carrying purebred Simmental fetuses, were blocked by live-weight, body condition score, expected calving date and fetal sex, and assigned to one of three groups: (1) control (CON; no induction treatment, n = 29); (2) induction with corticosteroids (CORT; n = 27); or (3) induction with corticosteroids plus prostaglandin (CORT + PG; n = 25). Interval from induction to calving in hours and calving ease on a scale of 1 to 5 were recorded. Vaginal mucus samples were collected on Day 21 and Day 42 after calving (Day 0) by means of a Metricheck and scored on a scale of 0 to 3. Reproductive tract examinations were conducted on Day 21 and Day 42 after calving, and uterine cytology samples were obtained on Day 21. A positive cytologic sample was defined as greater than 18% neutrophils in the sample obtained via a cytobrush technique. Cows were considered to have resumed ovarian cyclicity if the presence of the CL was confirmed. Data were analyzed using the Mixed (normally distributed data) and Genmod (nonparametric data) procedures of SAS (v. 9.3). The interval from treatment to calving was longer (P < 0.0001) for CON (161.9 +/- 15.12 hours) animals compared with CORT (39.7 +/- 11.64 hours) or CORT + PG (32.6 +/- 12.10 hours), which did not differ. Treatment did not affect calving difficulty score. There was also no difference in incidence of retained placenta between the three groups. At Day 21 postpartum, cytology score tended to be higher for both induced groups (48%) compared with the control animals (24%), but this was not the case for vaginal mucus score (CON 52%, CORT 70%, and CORT + PG 52%). A higher proportion of CON had an involuted uterus by Day 21 postpartum (69%) compared with both induced groups (CORT 48%, CORT + PG 32%). Day 21 ovarian cyclicity was higher in both CON (52%) and CORT (59%) compared with CORT + PG (29%). By Day 42, there was no difference in ovarian cyclicity or uterine involution between CON and CORT; however, a positive relationship was observed between uterine involution score on Day 21 and return to cyclicity on Day 42 in these two groups. There was a negative relationship between uterine involution score and return to cyclicity in the CORT + PG group, and these animals were slower (P < 0.05) to resume cyclicity by Day 42 with a larger proportion animals having evidence of having resumed postpartum ovarian cyclicity in both CON (P = 0.03) and CORT compared with CORT + PG on Day 42. In conclusion, the use of corticosteroid-based treatments is an effective strategy to advance parturition in full term dams and does not have a negative effect on calving progress or dam health. However, when prostaglandin is also included in the protocol, these treatments may lead to greater delay in uterine involution with increased chance of uterine infection and slower resumption of ovarian cyclicity. PMID- 26803184 TI - Sperm cryopreservation in different grouper subspecies and application in interspecific hybridization. AB - The present study established and confirmed an efficient technology for groupers: giant grouper Epinephelus lanceolatus, orange-spotted grouper E. coioides, seven band grouper, E. septemfasciatus, and kelp grouper E. moara sperm cryopreservation and successfully applied the cryopreserved E. lanceolatus sperm into interspecific hybridization with E. coioides. For both E. lanceolatus and E. coioides, the best motility of postthaw sperm were achieved using 6% to 10% DMSO, 6% to 16% propylene glycol, and 6% ethylene glycol as cryoprotectants. Furthermore, we have successfully applied this method into the other two species of E. septemfasciatus (74.56 +/- 5.45%) and E. moara (71.67 +/- 5.10%) sperm cryopreservation and obtained high motility, respectively. Computer-assisted sperm motion analysis showed that the postthaw sperm of the four species of grouper could keep 30 to 35 minutes motile state in nature seawater. And the freezing-thawing process decreased the sperm motility, speed, and longevity but did not significantly change the sperm movement pattern, and the progressive linear motion still was the dominant movement pattern. For the four species of grouper, the ultrastructural analysis showed 70% to 80% of the spermatozoa had intact morphology with a little of swelling; 20% to 30% were damaged, such as swelling or rupture of head, midpiece, and tail region; and 10% to 20% were severely damaged. Whereas, by the microscopic observation, more than 90% of the postthaw sperm presented normal morphology. In the artificial insemination and hybridization experiment, high fertilization rates and hatching rates were achieved when using 10% DMSO (88.7 +/- 5.3%, 85.3 +/- 7.4%) and 10% propylene glycol (86.8 +/- 3.3%, 83.1 +/- 6.6%), with no significant difference in comparison with control (92.2 +/- 1.4%, 87.9 +/- 4.2%). In addition, we found the embryos from postthaw sperm of E. lanceolatus and E. coioides eggs developed and grew normally as reported in previous study on hybridization of groupers (E. coioides * E. lanceolatus) using cryopreserved sperm. The results of the present study further validated the safety of the cryopreserved sperm in breeding production by assessing the fertilization capacity, embryo development, and larval growth. PMID- 26803183 TI - Cell viability of bovine spermatozoa subjected to DNA electroporation and DNAse I treatment. AB - Many mechanisms involved in sperm-mediated gene transfer (SMGT) are still unknown. It is still a matter of debate whether exogenous DNA fragments incorporated by the embryo are originated from those bound to the sperm membrane or by those that penetrated the intracellular compartment. In an attempt to elucidate the transmission mechanism of exogenous DNA molecules by sperm, some authors suggested a treatment with DNAse I to remove DNA molecules outside the sperm. But little is known regarding the effects of DNAse I treatment on sperm viability and its impact on sperm organelles. An important aspect of the SMGT technique is the amount of exogenous DNA incubated with sperm, which may influence the internalization rate. Due to the inconsistencies found in literature, this work aimed to contribute to bovine sperm physiology knowledge evaluating the effects of different DNA concentrations, electroporation, and DNAse I treatments on sperm viability characteristics, DNA uptake, and IVF. For that, the effects of different concentrations of exogenous DNA (250, 500 and 1000 ng/10(6) cells) and incubation or electroporation were tested on sperm functional characteristics and in vitro embryo production. No effect of DNA concentration was observed on uptake, plasma membrane integrity, and mitochondrial membrane potential. The addition of exogenous DNA induced a decrease on acrosomal lesion in the 500-ng group when compared to the control. Cells incubated with DNA, electroporated, and treated with DNAse I presented a deleterious influence on mitochondrial membrane potential. In vitro fertilization was made with 1000 ng of DNA, sperm cells incubated or electroporated followed by DNAse I treatment. No significant difference was found in cleavage rate. Blastocyst rates were 24.36% for the control; 19.65% for incubated; 3.5% for electroporated control; and 17.40% for electroporated. There is a significant difference in blastocyst rate between the control and electroporated control groups. The incubated group yielded five and electroporated two positive blastocysts evaluated by epifluorescence microscopy. Polymerase chain reaction screening shows 17% of positive embryos for incubation and 11% for electroporation. Fluorescence in situ hybridization showed the presence of exogenous gene in embryos. These results show that exogenous DNA molecules can be conducted by an intracellular mechanism. The SMGT protocol using electroporation and DNAse I treatment reduces sperm mitochondrial function, in vitro embryo production and increases sperm DNA fragmentation. PMID- 26803185 TI - Preferred strategies for workforce development: feedback from aged care workers. AB - Objective The aim of the present study was to investigate how aged care workers prefer to learn and be supported in continuing education and training activities. Methods Fifty-one workers in aged care facilities from metropolitan and rural settings across two states of Australia participated in a survey and interviews. Survey responses were analysed for frequencies and interview data provided explanations to the survey findings. Results The three most common ways workers were currently learning and prefer to continue to learn are: (1) everyday learning through work individually; (2) everyday learning through work individually assisted by other workers; and (3) everyday learning plus group training courses at work from the employer. The three most common types of provisions that supported workers in their learning were: (1) working and sharing with another person on the job; (2) direct teaching in a group (e.g. a trainer in a classroom at work); and (3) direct teaching by a workplace expert. Conclusions A wholly practice-based continuing education and training model is best suited for aged care workers. Two variations of this model could be considered: (1) a wholly practice-based model for individual learning; and (2) a wholly practice based model with guidance from coworkers or other experts. Although the model is preferred by workers and convenient for employers, it needs to be well resourced. What is known about the topic? Learning needs for aged care workers are increasing significantly because of an aging population that demands more care workers. Workforce development is largely 'episodic', based on organisational requirements rather than systematic life-long learning. This study is part of a larger 3-year Australian research to investigate models of continuing education training. What does this paper add? Based on an analysis of survey and interview data from 51 workers, the present study suggests effective models of workforce development for aged care workers. What are the implications for practitioners? The effectiveness of the suggested models necessitates a culture where aged care workers' advancement in the workplace is valued and supported. Those responsible for the development of these workers need to be adequately prepared for mentoring and coaching in the workplace. PMID- 26803186 TI - Azithromycin use and outcomes in severe sepsis patients with and without pneumonia. AB - PURPOSE: Studies investigating the association between macrolides and outcomes in both pulmonary and nonpulmonary critically ill patients are limited. We aimed to examine the association between azithromycin use and clinical outcomes in severe sepsis patients with and without pneumonia receiving mechanical ventilation. MATERIALS AND METHODS: A retrospective cohort of 105 patients admitted to an adult intensive care unit (ICU) with severe sepsis in an urban university hospital were included in the study. Multivariable linear regression was performed to assess the relationship between azithromycin use and the following outcomes: 28-day ICU-free days and 28-day ventilator-free days. RESULTS: In univariate analysis, patients receiving azithromycin had nearly 6 more ICU-free days on average than did patients not receiving azithromycin (P = .005). The increased ICU-free days remained in multivariable analysis adjusting for age, sex, race, ICU type, and presence of shock (P = .005). In stratified analysis examining the association of azithromycin use in severe sepsis patients without pneumonia (n = 74), the results were similar to the full cohort. CONCLUSION: Azithromycin was associated with more ICU-free days in severe sepsis patients with and without pneumonia. Further investigations are warranted to better elicit the association of macrolide use on clinical outcomes in severe sepsis patients, especially those without pneumonia. PMID- 26803188 TI - Visuospatial Neglect from Stroke Causing a Motor Vehicle Collision. PMID- 26803187 TI - Acute esophagitis for patients with local-regional advanced non small cell lung cancer treated with concurrent chemoradiotherapy. AB - PURPOSE: Esophagitis is common in patients treated with definitive radiotherapy for local-regional advanced non small cell lung cancer (NSCLC). The purpose of this study was to estimate the dose-effect relationship using clinical and dosimetric parameters in patients receiving intensity modulated radiotherapy (IMRT) and concomitant chemotherapy (CCT). METHODS: Between 2009 and 2013, 117 patients with stages IIB-IIIB NSCLC were treated in a multicenter randomized phase II trial with 2 cycles of induction chemotherapy followed by IMRT and CCT. The esophagitis was prospectively scored using the Common Toxicity Criteria 3.0. Clinical and dosimetric variables were analyzed for the correlation with grade ?2 esophagitis through logistic regression. RESULTS: Grade 2 esophagitis was experienced by 31 (27%). All models including gender, institution, a dosimetric parameter and a position parameter were significantly associated with esophagitis. The two models using the relative esophagus volume irradiated above 40 Gy (V40, OR=2.18/10% volume) or the length of esophagus irradiated above 40 Gy (L40, OR=4.03/5 cm) were optimal. The upper part of esophagus was more sensitive and females experienced more toxicity than men. CONCLUSION: V40 and L40 were most effective dosimetric predictors of grade ?2 esophagitis. The upper part of esophagus was more sensitive. PMID- 26803189 TI - Nonketotic Hyperglycemia Presenting as Monoballism. AB - BACKGROUND: Monoballismus is rarely seen clinically, but when observed, it is usually a manifestation of an acute cerebrovascular accident (CVA). We report a case of monoballismus observed in a patient without evidence of a CVA. CASE REPORT: We observed a case of monoballismus in a 60-year-old diabetic patient who had not had a stroke. The movement disorder resolved with improvement of the patient's hyperglycemia. Nonketotic hyperglycemia is an uncommon cause of ballismus. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should include the movement disorder of ballismus among the potential clues that a patient may be suffering an acute CVA. However, noncerebrovascular causes of ballismus exist. The movements manifest by a patient with ballismus should also lead the physician to consider the possibility not only of a CVA, but also neuroleptic malignant and serotonin syndromes. PMID- 26803190 TI - Long-Term Complications of Button Batteries in the Nose. AB - BACKGROUND: One of the common emergencies presenting to the emergency department is a child who has inserted a foreign body into their nose. Of the various things that children insert accidently, the most dangerous are button batteries. CASE REPORT: We followed up 11 cases of children with history of button battery insertion in the nose for 1 year. We found that all of the patients had developed a septal perforation; other sequelae included nasal adhesions and saddle nose. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Button batteries in the nose are dangerous and can lead to early complications with long-term consequences for the patients. Early diagnosis is required so that they can be removed as soon as possible to prevent the development of complications and long-term sequelae. PMID- 26803191 TI - Importance of the Emergency Medicine Application Components: The Medical Student Perception. AB - BACKGROUND: The National Resident Matching Program (NRMP) application has several elements. With limited time and resources, students must prioritize the key application elements on which to focus. It is unclear if medical students applying to emergency medicine (EM) prioritize the same items as program directors. OBJECTIVE: We sought to determine medical student perception of the importance of each factor of the NRMP application to an EM residency. METHODS: This was a cross-sectional study approved by the Institutional Review Board at an academic tertiary care Level I trauma center. A pilot-tested and validated survey tool was given to all medical students rotating in EM during an 18-month period. The students ranked each application item on a 5-point scale (1 = not important and 5 = very important) with verbal anchors. RESULTS: Of 136 medical students, 85.3% responded. Excluded were 31% who were not planning to apply to EM, leaving 80 responses for analysis. Items ranked higher were EM rotation grade, interview, clinical rotation grades, and letters of recommendation. Less emphasis was placed on Alpha Omega Alpha (AOA) honor society status, publication in medical literature, and personal statement. Items most agreed upon and believed to be most important by the students were EM rotation grade, interviews, and clinical rotation grades. CONCLUSIONS: This is similar to previously reported rankings by program directors. Although medical students agreed on the importance of most aspects of the NRMP application, areas of discordance included emphasis on extracurricular activities and AOA. This can have implications for medical student mentoring and advising. PMID- 26803192 TI - In the Limelight. PMID- 26803193 TI - The Effect of a Dedicated Psychiatric Team to Pediatric Emergency Mental Health Care. AB - BACKGROUND: Pediatric emergency department (PED) visits among children and adolescents with acute mental health needs have increased over the past decade with long wait times in the PED awaiting disposition. OBJECTIVE: The objective of this study was to evaluate the effect of a new pediatric mental health liaison program with the hypothesis that this model reduces length of stay (LOS) and hospitalization rates among pediatric mental health patients. METHODS: This was a pre- and postintervention retrospective study of the year prior to (June 2012 June 2013) and the year after (October 2013-October 2014) implementation of a new PED psychiatric team. All patients aged 1-18 years with a mental health International Classification of Diseases-9(th) Revision code were included. Patients who did not receive a Psychiatry consult in the PED were excluded. RESULTS: There were 83 encounters in the year prior to and 129 encounters in the year after the implementation of the liaison program. There was an increase in the suicidality of mental health patients during this time. There was a significant decrease in mean PED LOS of 27% (95% confidence interval [CI] 0-46%; p = 0.05) from pre- to postintervention period. The decrease in the proportion of patients admitted/transferred to an inpatient psychiatric facility in the postintervention year was statistically significant (odds ratio 0.35; 95% CI 0.17 0.71; p < 0.01). CONCLUSIONS: The use of a dedicated child psychiatrist and mental health social worker to the PED results in significantly decreased LOS and need for admission without any change in return visit rate. Larger, multicenter studies are needed to confirm these findings. PMID- 26803194 TI - Disseminated Herpes Zoster in Chronic Lymphocytic Leukemia. PMID- 26803195 TI - Observation Care: Ethical and Legal Considerations for the Emergency Physician. AB - BACKGROUND: The Medicare observation rules remain controversial despite Centers for Medicare and Medicaid Services revisions and the new 2-midnight rule. The increased financial risks for patients and heightened awareness of the rule have placed emergency physicians (EPs) at the center of the controversy. DISCUSSION: This article reviews the primary ethical and legal (particularly with respect to the Emergency Medical Treatment and Active Labor Act) implications of the existing observation rule for EPs and offers practical solutions for EPs faced with counseling patients on the meaning and ramifications of the observation rule. CONCLUSIONS: We conclude that while we believe it does not violate the intent of the Emergency Medical Treatment and Active Labor Act to respond to patient questions about their admission status, the observation rules challenge the ethical principles of transparency related to the physician-patient relationship and justice as fairness. Guidance for physicians is offered to improve transparency and patient fairness. PMID- 26803196 TI - Intrapulmonary arteriovenous anastomoses in dogs with severe Angiostrongylus vasorum infection: clinical, radiographic, and echocardiographic evaluation. AB - BACKGROUND: In both humans and dogs the pulmonary vasculature is able to recruit large-diameter anatomical intrapulmonary arteriovenous anastomoses (IPAVAs). In healthy people the opening of these anastomoses affects the degree of exercise induced increase in pulmonary arterial pressure. The presence of these IPAVAs can be demonstrated using saline contrast echocardiography. OBJECTIVES: The aims of the present study were to characterize severely affected, naturally infected dogs with Angiostrongylus vasorum, to evaluate if these dogs can open IPAVAs, and to assess if the recruitment of such anastomoses affects the severity of pulmonary hypertension (PH). ANIMALS: Eight client-owned dogs with severe A. vasorum infection were recruited. METHODS: Dogs with A. vasorum infection that presented with severe dyspnea and/or syncope were prospectively screened by echocardiography for the presence of PH and IPAVAs. Only severely affected dogs, based on a combination of clinical, radiographic and echocardiographic abnormalities, were enrolled. RESULTS: Opening of IPAVAs could be demonstrated in three dogs with no to moderate PH, and could not be demonstrated in five dogs with severe PH. In two dogs thoracic radiographs showed only mild interstitial changes, while computer tomography and postmortem examination revealed severe pulmonary interstitial and vascular disease. CONCLUSIONS: These results suggest that dogs may open IPAVAs and that opening of such anastomoses may play a regulatory role in the development of PH. There may be a marked discrepancy between radiographic changes and disease severity in A. vasorum. PMID- 26803197 TI - Cardiac-gated computed tomography angiography in three alpacas with complex congenital heart disease. AB - BACKGROUND: The prevalence of congenital heart disease is higher in camelids than in other domestic species and complex defects, often involving the great vessels, are more frequently encountered in llamas and alpacas than in other species. Some of these complex defects can be difficult to accurately characterize via echocardiography, the most commonly used diagnostic imaging technique to evaluate the heart in veterinary patients. Contrast-enhanced, electrocardiogram (ECG) gated computed tomography (CT) has proven utility for the evaluation of human patients with certain congenital heart defects, including those with conotruncal septation defects and other abnormalities involving the formation of the great vessels. METHODS: Three alpaca crias, 4 days, 5 weeks and 14 months of age were clinically evaluated and subjected to a complete color-flow Doppler echocardiogram and a contrast-enhanced ECG-gated CT. RESULTS: These alpacas exhibited a variety of clinical findings including lethargy, failure to thrive, exercise intolerance, heart murmur, and/or respiratory difficulty. All three crias were subsequently diagnosed with complex cardiac defects including pulmonary atresia with a ventricular septal defect (VSD), a truncus arteriosus with a large VSD, and a double outlet right ventricle with a large VSD and aortic hypoplasia. In each case, the diagnosis was confirmed by postmortem examination. CONCLUSION: Color flow echocardiographic evaluation identified all of the intra cardiac lesions and associated flow anomalies but contrast-enhanced ECG-gated CT permitted more accurate assessment of the morphology of the extracardiac structures and permitted a more precise determination of the exact nature and anatomy of the great vessels. PMID- 26803199 TI - Retrospective evaluation of intravenous premixed amiodarone use and adverse effects in dogs (17 cases: 2011-2014). AB - OBJECTIVE: The goal of this study was to evaluate the number and frequency of adverse effects in a population of clinical canine patients receiving Nexterone. ANIMALS: Seventeen canine patients receiving Nexterone (five of which were treated during cardiopulmonary arrest). METHODS: An electronic records search for canine patients receiving intravenous Nexterone at the Michigan State University Veterinary Teaching Hospital was performed and retrospectively evaluated for patient demographic information, pre- and post-treatment values for heart rate, blood pressure and rhythm diagnosis, as well as any documented adverse effects (hypotension, anaphylaxis, vomiting, phlebitis, and death). Data including the underlying cardiac or systemic disease, concurrent medications, as well as the final clinical diagnosis and treatment outcome were also recorded. RESULTS: No adverse effects were noted in this population of clinical canine patients receiving Nexterone. The median pre-treatment heart rate and blood pressure values were 160 bpm (range 120-300 bpm) and 105 mmHg (range 60-170 mmHg), respectively. After treatment, the median heart rate was significantly lower (120 bpm; range 68-172 bpm). The median blood pressure similar to the pre-treatment blood pressure (115 mmHg; range 100-150 mmHg). CONCLUSION: In this study of 17 dogs receiving the premixed formulation of injectable Nexterone, no dogs were found to have acute adverse side effects. Nexterone appears to be a safe drug choice for in-hospital treatment of canine arrhythmias. Further studies are needed to assess the efficacy and long-term effects of this medication and the ideal dosing protocol for various arrhythmias. PMID- 26803198 TI - The prevalence of the electrocardiographic J wave in the Petit Basset Griffon Vendeen compared to 10 different dog breeds. AB - INTRODUCTION: To investigate the prevalence and amplitudes of the electrocardiographic J wave in the Petit Basset Griffon Vendeen compared to 10 other dog breeds. ANIMALS: Electrocardiograms from 206 healthy dogs representing 11 dog breeds were included in the study. Besides Petit Basset Griffon Vendeen (PBGV; n = 23) 10 other dog breeds were included. MATERIALS AND METHODS: An electrocardiogram ruler was used for measuring the amplitudes of the J waves. The definition of a J wave was a positive deflection at the J point of >=0.1 mV in more than 1 lead of the bipolar standard limb leads (I, II, III) or the unipolar standard limb leads (aVL and aVF). RESULTS: The prevalence of J waves in the PBGV (n = 23) was 91% (n = 21, standard error (SE) = 5.9%), which was significantly higher compared to seven other dog breeds (p < 0.05). The overall prevalence of J waves in all 11 dog breeds (n = 206) was 43% (n = 89, robust SE = 7.8%). There was no significant difference in the prevalence between male and female dogs (p = 0.79). Neither did age (p = 0.22) nor heart rate (p = 0.25) significantly affect the prevalence of J wave. CONCLUSIONS: The PBGV had the highest prevalence of J waves and the highest amplitudes compared to 10 other dog breeds. However J waves were also seen in other breeds. Therefore, J waves may be considered a normal variant on the canine electrocardiogram and should not be interpreted as cardiac disease. PMID- 26803200 TI - Obsessive-Compulsive Symptoms as a Risk Factor for Suicidality in U.S. College Students. AB - PURPOSE: The purpose of this study was to assess the association of obsessive compulsive symptoms (OCS) with suicide risk among college students. METHODS: Subjects were 474 college students who attended mental health screenings at two private universities and completed multiple self-report questionnaires. RESULTS: Presence of one or more OCS was associated with an increased odds ratio of suicide risk of approximately 2.4, although this was no longer a significant risk factor when controlling for depressive symptoms. Of the OCS assessed, only obsessions about speaking or acting violently remained an independent risk factor for suicidality over and above depression. CONCLUSIONS: Although our study was cross-sectional in nature and thus cannot determine causality, increased burden of particular OCS symptom clusters, such as violent or aggressive obsessions, may increase risk among college students, for suicidal ideation. PMID- 26803202 TI - Comparison of group B streptococci colonization in vaginal and rectal specimens by culture method and polymerase chain reaction technique. AB - BACKGROUND: Streptococcus agalactiae (group B streptococci, GBS) is a colonizing microorganism in pregnant women and without causing symptoms. Colonization of GBS in the rectovaginal region in late of pregnancy is a risk factor for newborn diseases. GBS infection in newborn babies is acquired by the aspiration of infected amniotic fluid or vertical transmission during delivery through the birth canal. The aim of this study was determination of GBS prevalence among vaginal and anorectal specimens at gestation females by polymerase chain reaction (PCR) and culture-based methods. METHODS: In this study, 137 rectal and vaginal swabs were separately collected from women with gestational age 35-37 weeks from July 2013 to March 2014 at the teaching hospital of Razi, Ahvaz, Iran. All samples were enrichment in selective culture media Todd-Hewitt broth for 24 hours and recognized by standard culture using blood agar, phenotypic tests, and amplification of the CFB gene. RESULTS: Age range was 16-45 years (mean, 28.34 +/ 0.7 years). Of rectal samples, 42 (30.7%) were positive based on culture method and 57 (41.6%) samples were positive by PCR. Of 137 vaginal samples, 38 (27.7%) were positive by culture and 60 (43.8%) samples were positive by PCR. The chance of colonization with GBS was increased in women with a history of urinary tract infection. CONCLUSION: The frequency of GBS culture from rectal samples was higher than vaginal samples. However, the detection percentage of GBS using PCR from vaginal samples was higher than rectal samples. By contrast, the culture is a time-consuming method requiring at least 48 hours for GBS fully identification but PCR is a sensitive and rapid technique in detection of GBS, with the result was acquired during 3 hours. PMID- 26803201 TI - Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy in Perinatally HIV-Infected, Treatment-Naive Adolescents in Asia. AB - PURPOSE: About a third of untreated, perinatally HIV-infected children reach adolescence. We evaluated the durability and effectiveness of non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in this population. METHODS: Data from perinatally HIV-infected, antiretroviral naive patients initiated on NNRTI-based ART aged 10-19 years who had >=6 months of follow-up were analyzed. Competing risk regression was used to assess predictors of NNRTI substitution and clinical failure (World Health Organization Stage 3/4 event or death). Viral suppression was defined as a viral load <400 copies/mL. RESULTS: Data from 534 adolescents met our inclusion criteria (56.2% female; median age at treatment initiation 11.8 years). After 5 years of treatment, median height-for-age z score increased from -2.3 to -1.6, and median CD4+ cell count increased from 131 to 580 cells/mm(3). The proportion of patients with viral suppression after 6 months was 87.6% and remained >80% up to 5 years of follow-up. NNRTI substitution and clinical failure occurred at rates of 4.9 and 1.4 events per 100 patient-years, respectively. Not using cotrimoxazole prophylaxis at ART initiation was associated with NNRTI substitution (hazard ratio [HR], 1.5 vs. using; 95% confidence interval [CI] = 1.0-2.2; p = .05). Baseline CD4+ count <=200 cells/mm(3) (HR, 3.3 vs. >200; 95% CI = 1.2-8.9; p = .02) and not using cotrimoxazole prophylaxis at ART initiation (HR, 2.1 vs. using; 95% CI = 1.0-4.6; p = .05) were both associated with clinical failure. CONCLUSIONS: Despite late ART initiation, adolescents achieved good rates of catch-up growth, CD4+ count recovery, and virological suppression. Earlier ART initiation and routine cotrimoxazole prophylaxis in this population may help to reduce current rates of NNRTI substitution and clinical failure. PMID- 26803203 TI - Analogs of farnesyl diphosphate alter CaaX substrate specificity and reactions rates of protein farnesyltransferase. AB - Attempts to identify the prenyl-proteome of cells or changes in prenylation following drug treatment have used 'clickable' alkyne-modified analogs of the lipid substrates farnesyl- and geranylgeranyl-diphosphate (FPP and GGPP). We characterized the reactivity of four alkyne-containing analogs of FPP with purified protein farnesyltransferase and a small library of dansylated peptides using an in vitro continuous spectrofluorimetric assay. These analogs alter prenylation specificity and reactivity suggesting that in vivo results obtained using these FPP analogs should be interpreted cautiously. PMID- 26803205 TI - GnRH agonist trigger for the induction of oocyte maturation in GnRH antagonist IVF cycles: a SWOT analysis. AB - Gonadotrophin releasing hormone agonist (GnRHa) trigger is effective in the induction of oocyte maturation and prevention of ovarian hyperstimulation syndrome during IVF treatment. This trigger concept, however, results in early corpora lutea demise and consequently luteal phase dysfunction and impaired endometrial receptivity. The aim of this strenghths, weaknesses, opportunities and threats analysis was to summarize the progress made over the past 15 years to optimize ongoing pregnancy rates after GnRHa trigger. The advantages and potential drawbacks of this type of triggering are reviewed. The current approach to the management of GnRHa trigger in autologous cycles is based on the peak serum oestradiol level or follicle number and aims at a fresh embryo transfer or a segmentation approach with elective cryopreservation policy. We recommend intensive luteal support with transdermal oestradiol and intramuscular progesterone alone if peak serum oestradiol is 4000 or more pg/ml after GnRHa trigger or dual trigger with GnRHa and HCG 1000 IU if peak serum oestradiol is less than 4000 pg/mL. On the contrary, we recommend HCG 1500 IU 35 h after GnRHa trigger if there are less than 25 follicles, or freeze all oocytes or embryos if there are over 25 follicles. PMID- 26803204 TI - Identification of initial leads directed at the calmodulin-binding region on the Src-SH2 domain that exhibit anti-proliferation activity against pancreatic cancer. AB - Cellular calmodulin binds to the SH2 domain of Src kinase, and upon Fas activation it recruits Src into the death-inducing signaling complex. This results in Src-ERK activation of cell survival pathway through which pancreatic cancer cells survive and proliferate. We had proposed that the inhibition of the interaction of calmodulin with Src-SH2 domain is an attractive strategy to inhibit the proliferation of pancreatic cancer. Thus we have performed screening of compound libraries by a combination of methods and identified some compounds (initial leads) that target the calmodulin-binding region on the SH2 domain and inhibit the proliferation of pancreatic cancer cells in in vitro assays. Most of these compounds also exhibited varying degrees of cytotoxicity when tested against immortalized breast epithelial cell line (MCF10A). These initial leads are likely candidates for development in targeted delivery of compounds to cancer cells without affecting normal cells. PMID- 26803206 TI - Anti-Mullerian hormone in breast cancer patients treated with chemotherapy: a retrospective evaluation of subsequent pregnancies. AB - Few studies have reported reproductive outcomes after breast cancer chemotherapy. The relationship between anti-Mullerian hormone (AMH) concentrations and the occurrence of subsequent pregnancies in women after chemotherapy for breast cancer was investigated. Women aged 18-43 years treated with chemotherapy for invasive breast cancer between May 2005 and January 2011 were retrospectively identified. Exclusion criteria were previous gonadotoxic treatment, oophorectomy or hysterectomy. Measurement of AMH took place before, during chemotherapy and at distant time points after the end of chemotherapy (4 months to 5.5 years). Seventeen out of 134 patients experienced 28 spontaneous pregnancies (median follow-up: 59 months). Neither baseline AMH (divided into quartiles) nor end-of chemotherapy AMH (detectable versus undetectable) were significantly associated with the occurrence of pregnancy. Chemotherapy regimen with anthracyclines was associated with a greater probability of pregnancy compared with a taxane containing regimen (hazard ratio 4.75; (95% CI 1.76 to 12.8); P = 0.002). Five year disease-free survival and overall survival rates were 60% (95% CI: 51 to 70; relapse, n = 48) and 88% (95% CI 82 to 95; deaths, n = 21), respectively. AMH did not predict the occurrence of pregnancy. Additional studies assessing ovarian reserve and reproductive outcomes after breast cancer are required. PMID- 26803207 TI - Opiate receptor blockade on human granulosa cells inhibits VEGF release. AB - The objectives of this study were to determine whether the main opioid receptor (OPRM1) is present on human granulosa cells and if exogenous opiates and their antagonists can influence granulosa cell vascular endothelial growth factor (VEGF) production via OPRM1. Granulosa cells were isolated from women undergoing oocyte retrieval for IVF. Complementary to the primary cells, experiments were conducted using COV434, a well-characterized human granulosa cell line. Identification and localization of opiate receptor subtypes was carried out using Western blot and flow cytometry. The effect of opiate antagonist on granulosa cell VEGF secretion was assessed by enzyme-linked immunosorbent assay. For the first time, the presence of OPRM1 on human granulosa cells is reported. Blocking of opiate signalling using naloxone, a specific OPRM1 antagonist, significantly reduced granulosa cell-derived VEGF levels in both COV434 and granulosa-luteal cells (P < 0.01). The presence of opiate receptors and opiate signalling in granulosa cells suggest a possible role in VEGF production. Targeting this signalling pathway could prove promising as a new clinical option in the prevention and treatment of ovarian hyperstimulation syndrome. PMID- 26803208 TI - Cognitive Adaptation under Stress: A Case for the Mineralocorticoid Receptor. AB - Corticosteroid hormones, released during stressful encounters, have profound and far-reaching effects on cognition. They are often thought to accomplish these effects primarily via glucocorticoid receptors (GR), but recent findings from rodent and human studies argue for an additional, critical role of the mineralocorticoid receptor (MR) in cognitive changes in response to stress. We propose that the MR initiates rapid changes in the recruitment of specific neural systems, inducing a shift towards cognitively less-demanding processing and allowing a quick and adequate response to the situation. In combination with slower and longer-lasting actions mediated by GR, this shift leads to optimal coping with the ongoing stressful event. PMID- 26803209 TI - Analysis of Hippo and TGFbeta signaling in polarizing epithelial cells and mouse embryos. AB - The Hippo signaling pathway is involved in numerous biological events ranging from early development to organogenesis and when disrupted, impacts various human diseases including cancer. The Hippo pathway also interacts with and controls the activity of other signaling pathways such as the TGFbeta/Smad pathway, in which Hippo pathway activity influences the subcellular localization of Smad transcription factors. Here, we describe techniques for examining crosstalk between Hippo and TGFbeta signaling in polarizing mammary epithelial cells. In addition, we provide detailed methods for analyzing the subcellular localization of the Hippo pathway effectors, Taz and Yap using both in vitro cultured epithelial cells and in vivo in pregastrulation mouse embryos. PMID- 26803210 TI - Carotid extra-medial thickness does not predict adverse cardiovascular outcomes in high-risk adults. PMID- 26803211 TI - Multimedia exposures to arsenic and lead for children near an inactive mine tailings and smelter site. AB - Children living near contaminated mining waste areas may have high exposures to metals from the environment. This study investigates whether exposure to arsenic and lead is higher in children in a community near a legacy mine and smelter site in Arizona compared to children in other parts of the United States and the relationship of that exposure to the site. Arsenic and lead were measured in residential soil, house dust, tap water, urine, and toenail samples from 70 children in 34 households up to 7 miles from the site. Soil and house dust were sieved, digested, and analyzed via ICP-MS. Tap water and urine were analyzed without digestion, while toenails were washed, digested and analyzed. Blood lead was analyzed by an independent, certified laboratory. Spearman correlation coefficients were calculated between each environmental media and urine and toenails for arsenic and lead. Geometric mean arsenic (standard deviation) concentrations for each matrix were: 22.1 (2.59) ppm and 12.4 (2.27)ppm for soil and house dust (<63MUm), 5.71 (6.55)ppb for tap water, 14.0 (2.01)MUg/L for specific gravity-corrected total urinary arsenic, 0.543 (3.22)ppm for toenails. Soil and vacuumed dust lead concentrations were 16.9 (2.03)ppm and 21.6 (1.90) ppm. The majority of blood lead levels were below the limit of quantification. Arsenic and lead concentrations in soil and house dust decreased with distance from the site. Concentrations in soil, house dust, tap water, along with floor dust loading were significantly associated with toenail and urinary arsenic but not lead. Mixed models showed that soil and tap water best predicted urinary arsenic. In our study, despite being present in mine tailings at similar levels, internal lead exposure was not high, but arsenic exposure was of concern, particularly from soil and tap water. Naturally occurring sources may be an additional important contributor to exposures in certain legacy mining areas. PMID- 26803212 TI - Bioreactor with Ipomoea hederifolia adventitious roots and its endophyte Cladosporium cladosporioides for textile dye degradation. AB - In vitro grown untransformed adventitious roots (AR) culture of Ipomoea hederifolia and its endophytic fungus (EF) Cladosporium cladosporioides decolorized Navy Blue HE2R (NB-HE2R) at a concentration of 20 ppm up to 83.3 and 65%, respectively within 96h. Whereas the AR-EF consortium decolorized the dye more efficiently and gave 97% removal within 36h. Significant inductions in the enzyme activities of lignin peroxidase, tyrosinase and laccase were observed in roots, while enzymes like tyrosinase, laccase and riboflavin reductase activities were induced in EF. Metabolites of dye were analyzed using UV-vis spectroscopy, FTIR and gas chromatography-mass spectrometry. Possible metabolic pathways of NB HE2R were proposed with AR, EF and AR-EF systems independently. Looking at the superior efficacy of AR-EF system, a rhizoreactor was developed for the treatment of NB-HE2R at a concentration of 1000 ppm. Control reactor systems with independently grown AR and EF gave 94 and 85% NB-HE2R removal, respectively within 36h. The AR-EF rhizoreactor, however, gave 97% decolorization. The endophyte colonization additionally increased root and shoot lengths of candidate plants through mutualism. Combined bioreactor strategies can be effectively used for future eco-friendly remediation purposes. PMID- 26803213 TI - Health impact assessment of transport policies in Rotterdam: Decrease of total traffic and increase of electric car use. AB - BACKGROUND: Green house gas (GHG) mitigation policies can be evaluated by showing their co-benefits to health. METHOD: Health Impact Assessment (HIA) was used to quantify co-benefits of GHG mitigation policies in Rotterdam. The effects of two separate interventions (10% reduction of private vehicle kilometers and a share of 50% electric-powered private vehicle kilometers) on particulate matter (PM2.5), elemental carbon (EC) and noise (engine noise and tyre noise) were assessed using Years of Life Lost (YLL) and Years Lived with Disability (YLD). The baseline was 2010 and the end of the assessment 2020. RESULTS: The intervention aimed at reducing traffic is associated with a decreased exposure to noise resulting in a reduction of 21 (confidence interval (CI): 11-129) YLDs due to annoyance and 35 (CI: 20-51) YLDs due to sleep disturbance for the population per year. The effects of 50% electric-powered car use are slightly higher with a reduction of 26 (CI: 13-116) and 41 (CI: 24-60) YLDs, respectively. The two interventions have marginal effects on air pollution, because already implemented traffic policies will reduce PM2.5 and EC by around 40% and 60% respectively, from 2010 to 2020. DISCUSSION: The evaluation of planned interventions, related to climate change policies, targeting only the transport sector can result in small co-benefits for health, if the analysis is limited to air pollution and noise. This urges to expand the analysis by including other impacts, e.g. physical activity and well-being, as a necessary step to better understanding consequences of interventions and carefully orienting resources useful to build knowledge to improve public health. PMID- 26803214 TI - Road traffic noise effects on cardiovascular, respiratory, and metabolic health: An integrative model of biological mechanisms. AB - BACKGROUND: Road traffic noise is a major public health issue, given the documented association with several diseases and the growing number of exposed persons all over the world. The effects widely investigated pertain to cardiovascular health, and to a lesser extent to respiratory and metabolic health. The epidemiological design of most studies has made it possible to ascertain long-term associations of urban noise with a number of cardiovascular, respiratory, and metabolic disorders and diseases; additionally, time series studies have reported short-term associations. OBJECTIVES: To review the various biological mechanisms that may account for all long-term as well as short-term associations between road traffic noise and cardiovascular, respiratory, and metabolic health. We also aimed to review the neuroendocrine processes triggered by noise as a stressor and the role of the central nervous system in noise induced autonomic responses. METHODS: Review of the literature on road traffic noise, environmental noise in general, psychosomatics, and diseases of the cardiovascular, respiratory, and metabolic systems. The search was done using PubMed databases. DISCUSSION: We present a comprehensive, integrative stress model with all known connections between the body systems, states, and processes at both the physiological and psychological levels, which allows to establish a variety of biological pathways linking environmental noise exposure with health outcomes. CONCLUSIONS: The long- and short-term associations between road traffic noise and health outcomes found in latest noise research may be understood in the light of the integrative model proposed here. PMID- 26803215 TI - Evidence for the involvement of hydraulic root or shoot adjustments as mechanisms underlying water deficit tolerance in two Sorghum bicolor genotypes. AB - Sorghum bicolor (L.) Moench is an ancient drought-tolerant crop with potential to sustain high yields even in those environments where water is limiting. Understanding the performance of this species in early phenological stages could be a useful tool for future yield improvement programs. The aim of this work was to study the response of Sorghum seedlings under water deficit conditions in two genotypes (RedLandB2 and IS9530) that are currently employed in Argentina. Morphological and physiological traits were studied to present an integrated analysis of the shoot and root responses. Although both genotypes initially developed a conserved and indistinguishable response in terms of drought tolerance parameters (growth rate, biomass reallocation, etc.), water regulation displayed different underlying strategies. To avoid water loss, both genotypes adjusted their plant hydraulic resistance at different levels: RedLandB2 regulated shoot resistance through stomata (isohydric strategy), while IS9530 controlled root resistance (anisohydric strategy). Moreover, only in IS9530 was root hydraulic conductance restricted in the presence of HgCl2, in agreement with water movement through cell-to-cell pathways and aquaporins activity. The different responses between genotypes suggest a distinct strategy at the seedling stage and add new information that should be considered when evaluating Sorghum phenotypic plasticity in changing environments. PMID- 26803216 TI - Mixed cropping has the potential to enhance flood tolerance of drought-adapted grain crops. AB - Recently, the occurrences of extreme flooding and drought, often in the same areas, have increased due to climate change. Wetland plant species are known to oxygenate their rhizospheres by releasing oxygen (O2) from their roots. We tested the hypothesis that wetland species could help upland species under flood conditions; that is, O2 released from the wetland crop roots would ameliorate rhizosphere O2-deficient stress and hence facilitate upland crop root function. Flooding tolerance of upland-adapted staple crops-pearl millet (Pennisetum glaucum) and sorghum (Sorghum bicolor) mix-cropped with rice (Oryza spp.) was investigated in glasshouse and laboratory. We found a phenomenon that strengthens the flood tolerance of upland crops when two species-one wetland and one drought tolerant-were grown using the mixed cropping technique that results in close tangling of their root systems. This technique improved the photosynthetic and transpiration rates of upland crops subjected to flood stress (O2-deficient nutrient culture). Shoot relative growth rates during the flooding period (24 days) tended to be higher under mixed cropping compared with single cropping. Radial oxygen loss from the wetland crop roots might be contributed to the phenomenon observed. Mixed cropping of wet and dryland crops is a new concept that has the potential to overcome flood stress under variable environmental conditions. PMID- 26803217 TI - New Atlanta Classification of acute pancreatitis in intensive care unit: Complications and prognosis. AB - BACKGROUND: The updated Atlanta Classification of acute pancreatitis (AP) in adults defined three levels of severity according to the presence of local and/or systemic complications and presence and length of organ failure. No study focused on complications and mortality of patients with moderately severe AP admitted to intensive care unit (ICU). The main aim of this study is to describe the complications developed and outcomes of these patients and compare them to those with severe AP. METHODS: Prospective, observational study. We included patients with acute moderately severe or severe AP admitted in a medical-surgical ICU during 5years. We collected demographic data, admission criteria, pancreatitis etiology, severity of illness, presence of organ failure, local and systemic complications, ICU length of stay, and mortality. RESULTS: Fifty-six patients were included: 12 with moderately severe AP and 44 with severe. All patients developed some kind of complications without differences on complications rate between moderately severe or severe AP. All the patients present non-infectious systemic complications, mainly acute respiratory failure and hemodynamic failure. 82.1% had an infectious complication, mainly non-pancreatic infection (66.7% on moderately severe AP vs. 79.5% on severe, p=0.0443). None of the patients with moderately severe AP died during their intensive care unit stay vs. 29.5% with severe AP (p=0.049). CONCLUSIONS: Moderately severe AP has a high rate of complications with similar rates to patients with severe AP admitted to ICU. However, their ICU mortality remains very low, which supports the existence of this new group of pancreatitis according to their severity. PMID- 26803218 TI - Trends in mercury wet deposition and mercury air concentrations across the U.S. and Canada. AB - This study examined the spatial and temporal trends of mercury (Hg) in wet deposition and air concentrations in the United States (U.S.) and Canada between 1997 and 2013. Data were obtained from the National Atmospheric Deposition Program (NADP) and Environment Canada monitoring networks, and other sources. Of the 19 sites with data records from 1997-2013, 53% had significant negative trends in Hg concentration in wet deposition, while no sites had significant positive trends, which is in general agreement with earlier studies that considered NADP data up until about 2010. However, for the time period 2007-2013 (71 sites), 17% and 13% of the sites had significant positive and negative trends, respectively, and for the time period 2008-2013 (81 sites) 30% and 6% of the sites had significant positive and negative trends, respectively. Non significant positive tendencies were also widespread. Regional trend analyses revealed significant positive trends in Hg concentration in the Rocky Mountains, Plains, and Upper Midwest regions for the recent time periods in addition to significant positive trends in Hg deposition for the continent as a whole. Sulfate concentration trends in wet deposition were negative in all regions, suggesting a lower importance of local Hg sources. The trend in gaseous elemental Hg from short-term datasets merged as one continuous record was broadly consistent with trends in Hg concentration in wet deposition, with the early time period (1998-2007) producing a significantly negative trend (-1.5+/-0.2%year(-1)) and the recent time period (2008-2013) displaying a flat slope (-0.3+/-0.1%year( 1), not significant). The observed shift to more positive or less negative trends in Hg wet deposition primarily seen in the Central-Western regions is consistent with the effects of rising Hg emissions from regions outside the U.S. and Canada and the influence of long-range transport in the free troposphere. PMID- 26803219 TI - Effect of chromium oxide (III) nanoparticles on the production of reactive oxygen species and photosystem II activity in the green alga Chlamydomonas reinhardtii. AB - With the growth of nanotechnology and widespread use of nanomaterials, there is an increasing risk of environmental contamination by nanomaterials. However, the potential implications of such environmental contamination are hard to evaluate since the toxicity of nanomaterials if often not well characterized. The objective of this study was to evaluate the toxicity of a chromium-based nanoparticle, Cr2O3-NP, used in a wide diversity of industrial processes and commercial products, on the unicellular green alga Chlamydomonas reinhardtii. The deleterious impacts of Cr2O3-NP were characterized using cell density measurements, production of reactive oxygen species (ROS), esterase enzymes activity, and photosystem II electron transport as indicators of toxicity. Cr2O3 NP exposure inhibited culture growth and significantly lowered cellular Chlorophyll a content. From cell density measurements, EC50 values of 2.05+/-0.20 and 1.35+/-0.06gL(-1) Cr2O3-NP were obtained after 24 and 72h of exposure, respectively. In addition, ROS levels were increased to 160.24+/-2.47% and 59.91+/-0.15% of the control value after 24 and 72h of exposition to 10gL(-1) Cr2O3-NP. At 24h of exposure, the esterase activity increased to 160.24% of control value, revealing a modification of the short-term metabolic response of algae to Cr2O3-NP exposure. In conclusion, the metabolism of C. reinhardtii was the most sensitive to Cr2O3-NP after 24h of treatment. PMID- 26803220 TI - Development of a green remediation tool in Japan. AB - The green remediation assessment tool for Japan (GRATJ) presented in this study is a spreadsheet-based software package developed to facilitate comparisons of the environmental impacts associated with various countermeasures against contaminated soil in Japan. This tool uses a life-cycle assessment-based model to calculate inventory inputs/outputs throughout the activity life cycle during remediation. Processes of 14 remediation methods for heavy metal contamination and 12 for volatile organic compound contamination are built into the tool. This tool can evaluate 130 inventory inputs/outputs and easily integrate those inputs/outputs into 9 impact categories, 4 integrated endpoints, and 1 index. Comparative studies can be performed by entering basic data associated with a target site. The integrated results can be presented in a simpler and clearer manner than the results of an inventory analysis. As a case study, an arsenic contaminated soil remediation site was examined using this tool. Results showed that the integrated environmental impacts were greater with onsite remediation methods than with offsite ones. Furthermore, the contributions of CO2 to global warming, SO2 to urban air pollution, and crude oil to resource consumption were greater than other inventory inputs/outputs. The GRATJ has the potential to improve green remediation and can serve as a valuable tool for decision makers and practitioners in selecting countermeasures in Japan. PMID- 26803221 TI - Environmental forensics in groundwater coupling passive sampling and high resolution mass spectrometry for screening. AB - One of the difficulties encountered when monitoring groundwater quality is low and fluctuating concentration levels and complex mixtures of micropollutants, including emerging substances or transformation products. Combining passive sampling techniques with analysis by high resolution mass spectrometry (HRMS) should improve environmental metrology. Passive samplers accumulate compounds during exposure, which improves the detection of organic compounds and integrates pollution fluctuations. The Polar Organic Chemical Integrative Sampler (POCIS) were used in this study to sequester polar to semi-polar compounds. The methodology described here improves our knowledge of environmental pollution by highlighting and identifying pertinent compounds to be monitored in groundwater. The advantage of combining these two approaches is demonstrated on two different sites impacted by agricultural and/or urban pollution sources where groundwater was sampled for several months. Grab and passive sampling were done and analyzed by liquid chromatography coupled to a hybrid quadrupole time-of-flight mass spectrometer (LC-QTOF). Various data processing approaches were used (target, suspect and non-target screening). Target screening was based on research from compounds listed in a homemade database and suspect screening used a database compiled using literature data. The non-target screening was done using statistical tools such as principal components analysis (PCA) with direct connections between original chromatograms and ion intensity. Trend plots were used to highlight relevant compounds for their identification. The advantage of using POCIS to improve screening of polar organic compounds was demonstrated. Compounds undetected in water samples were detected with these tools. The subsequent data processing identified sentinel molecules, molecular clusters as compounds never revealed in these sampling sites, and molecular fingerprints. Samples were compared and multidimensional visualization of chemical patterns such as molecular fingerprints and recurrent or specific markers of each site were given. PMID- 26803222 TI - Prognostic factors in two-stage flexor tendon reconstruction: Is it possible to predict surgical failure? AB - INTRODUCTION: Two-stage surgical reconstruction of the flexor tendons by the Hunter technique is the salvage option in case of old tears or a severely damaged fibro-osseous canal. HYPOTHESIS: The identification of poor prognostic factors during the assessment of injuries at presentation could help determine indications and predict failures. MATERIALS AND METHODS: We report a retrospective single center series of reconstruction of zone 2 of the flexor digitorum profundus of the long fingers between 2000 and 2012, in 22 patients, mean age 33 years old with a mean follow-up of 36.4 months. RESULTS: The total active range of motion (TAM) of the rays was 110 degrees with a mean range of motion of the PIP and DIP of 71 degrees and 39 degrees respectively. Sixty three percent of patients were satisfied and 73% returned to their professional activities. A group with good and fair results was determined based on the Strickland classification (68%, 15 patients, mean TAM 126 degrees , mean QuickDASH 22.6) and a group with poor results (32%, 7 patients, mean TAM 77 degrees , mean QuickDASH 43.4). The factors of a poor prognosis were associated injuries to the extensor apparatus, infection (phlegmon) (P=0.023) and joint injuries (P=0.09). DISCUSSION: There are no factors in the literature to predict a poor prognosis except for reconstruction of the flexor pollicis longus. A simplified procedure could provide better results in patients with associated injuries to the extensor apparatus, infection (phlegmon) or osteoarticular damage, in terms of the duration of physical therapy, additional surgery and overall socioeconomic cost. The results in the literature of superficialis finger reconstruction are significantly better (P<0.001). CONCLUSION: Although the Hunter technique is still the reference procedure for the reconstruction of flexor tendons, our study identified prognostic factors of poor functional results such as infection and associated extensor apparatus damage, which should orient the surgeon towards a simplified technique such as the superficialis finger procedure. LEVEL OF EVIDENCE: IV: retrospective study. PMID- 26803223 TI - New modalities of pain treatment after outpatient orthopaedic surgery. AB - Postoperative pain relief is one of the cornerstones of success of orthopaedic surgery. Development of new minimally-invasive surgical procedures, as well as improvements in pharmacological and local and regional techniques should result in optimal postoperative pain control for all patients. The analgesic strategy has to be efficient, with minimal side effects, and be easy to manage at home. Multimodal analgesia allows for a reduction of opiate use and thereby its side effects. Local and regional analgesia is a major component of this multimodal strategy, associated with optimal pain relief, even upon mobilization, and it has beneficial effects on postoperative recovery. Ultrasound guidance improves the success rate of distal nerve blocks and makes distal selective blockade possible, helping to preserve the limb's motility. Besides peripheral nerve blocks, local infiltration (incisional and/or intra-articular) is also important to consider. Duration of the nerve blockade is limited after a single injection. This must be taken into consideration to avoid the recurrence of pain when the patient returns home. Continuous perineural blocks using catheters are an option that can be easily managed at home with monitoring by home-care nurses. Extended-release liposomal bupivacaine and adjuvants such as dexamethasone could significantly enhance the duration of the sensory block, thereby reducing the indications for pain pumps. Non-pharmacological approaches, such as cryotherapy, hypnosis and acupuncture should not be ignored. PMID- 26803224 TI - Cost-effectiveness model comparing dual-mobility to fixed-bearing designs for total hip replacement in France. AB - BACKGROUND: Instability is among the main causes of total hip arthroplasty (THA) failure. In clinical studies, THA with a dual-mobility cup (THA-DM) decreased the risk of instability after primary THA compared to THA with a fixed-bearing design (THA-FB). However, whether THA-DM is more cost-effective than THA-FB has not been established using Markov modelling with determination of the incremental cost effectiveness ratio (ICER). The objectives of this work were to: (1) measure the efficiency of these two options, (2) use the nationwide hospital electronic database (PMSI) to estimate direct costs of dislocations and revisions for instability, and (3) conduct deterministic and probabilistic sensitivity analyses to estimate potential mean annual cost-savings in France. HYPOTHESIS: We hypothesised that primary THA-DM was cost-saving compared to primary THA-FB. MATERIAL AND METHODS: In the database, we identified 80,405 patients who had THA in 2009 and we collected their outcomes over 4 years (2009-2012). Cost effectiveness was assessed based on the costs of resources used for all consequences of prosthetic dislocation and paid for by the statutory health insurance system or other sources. RESULTS: THA-DM was associated with a relative risk of dislocation of 0.4 versus THA-FB. This risk difference translated into 3283 fewer dislocations per 100,000 patients with THA-DM. The corresponding cost savings for the 140,000 primary THA procedures done in France annually was 39.62 million Euros. A relative risk of 0.2 would yield annual cost-savings of 56.28 million Euros. In the probabilistic sensitivity analysis, THA-DM was the less costly option under all hypotheses, with potential maximum cost-savings of more than 100 million Euros per year in France. DISCUSSION: This comparative cost effectiveness analysis suggests that THA-DM may induce substantial cost-savings compared to THA-FB. This possibility should be assessed by long-term clinical studies of new-generation DM prostheses. PMID- 26803225 TI - Performance evaluation of a retrofit digital detector-based mammography system. AB - A retrofit flat panel detector was integrated with a GE DMR+ analog mammography system and characterized using detective quantum efficiency (DQE). Technical system performance was evaluated using the European Guidelines protocol, followed by a limited evaluation of clinical image quality for 20 cases using image quality criteria in the European Guidelines. Optimal anode/filter selections were established using signal difference-to-noise ratio measurements. Only small differences in peak DQE were seen between the three anode/filter settings, with an average value of 0.53. For poly(methyl methacrylate) (PMMA) thicknesses above 60 mm, the Rh/Rh setting was the optimal anode/filter setting. The system required a mean glandular dose of 0.54 mGy at 30 kV Rh/Rh to reach the Acceptable gold thickness limit for 0.1 mm details. Imaging performance of the retrofit unit with the GE DMR+ is notably better than of powder based computed radiography systems and is comparable to current flat panel FFDM systems. PMID- 26803226 TI - Sphingosine 1-phospate differentially modulates maturation and function of human Langerhans-like cells. AB - BACKGROUND: As mediators between innate and adaptive immune responses, Langerhans cells (LCs) are in the focus of recent investigations to determine their role in allergic inflammatory diseases like allergic contact dermatitis and atopic dermatitis. Sphingosine 1-phosphate (S1P) is a crucial lipid mediator in the skin and potentially interferes with LC homeostasis but also functional properties, such as cytokine release, migration and antigen-uptake which are considered to be key events in the initiation and maintenance of pathological disorders. OBJECTIVE: Here, we used human Langerhans-like cells to study the influence of S1P-mediated signalling on LC maturation, cytokine release, migration and endocytosis. METHODS: Immature Langerhans-like cells were generated from the human acute myeloid leukaemia cell line MUTZ-3 (MUTZ-LCs) and human primary monocytes (MoLCs). S1P receptor expression was determined by quantitative RT-PCR and western blotting. Expression of maturation markers were investigated by flow cytometry. The influence of S1P signalling on cytokine release was quantified by ELISA. Migration assays and FITC-dextran uptake in the presence of S1P, specific S1 P receptor agonists and antagonists as well as fingolimod (FTY720) were analysed through fluorescence microscopy and flow cytometry. RESULTS: S1P receptor protein expression was confirmed for S1P1, S1P2 and S1P4 in MUTZ-LCs and S1P1 and S1P2 in MoLCs. In mature cells S1P receptors were downregulated. S1P did not induce maturation in MUTZ-LCs, whereas in MoLCs CD83 and CD86 were slightly upregulated. IL-8 release of MUTZ-LCs matured in the presence of S1P was not altered, however, reduced IL-6 and IL-12p70 levels were observed in mature MoLCs. Interestingly, immature MUTZ-LCs revealed a significantly increased S1P-dependent migratory capacity, whereas CCL20 induced migration was significantly decreased in the presence of S1P. Furthermore, migratory capacity towards CCL21 in mature MUTZ-LCs but not MoLCs was significantly lower when cells were stimulated with S1P. S1P, FTY720 and specific S1P receptor agonists did not modulate the endocytotic capacity of immature MUTZ-LCs and MoLCs. These findings were further supported by testing specific antagonists of S1P1-4 in the absence or presence of S1P. CONCLUSION: Our data demonstrate that S1P regulates key events of human LC maturation including cytokine release and migration. These findings are of particular importance when considering the potential use of S1P in inflammatory skin disorders. PMID- 26803227 TI - Response to "Comment on Skin Manifestations of Chronic Kidney Disease". PMID- 26803228 TI - Clinical Pathway for Patients with Acute or Chronic Urticaria: A Consensus Statement of the Andalusian Section of the Spanish Academy of Dermatology and Venereology (AEDV). AB - Attention has been focused on new ways to understand and manage urticaria ever since the recent addition of novel drugs to the therapeutic arsenal, the updating of clinical practice guidelines, and the publication of pathophysiologic insights. The Andalusian Section of the Spanish Academy of Dermatology and Venereology (AEDV) has developed a clinical pathway that defines quality-of-care characteristics and makes recommendations on decision-making affecting patients with urticaria. We present a patient-centered approach to care, in which the patient's clinical pathway through the health care system includes links between primary and hospital care to ensure continuity-a key feature of quality. PMID- 26803229 TI - Microplastics in the Mediterranean Sea: Deposition in coastal shallow sediments, spatial variation and preferential grain size. AB - Marine litter loads in sea compartments are an emergent issue due to their ecological and biological consequences. This study addresses microplastic quantification and morphological description to test spatial differences along an anthropogenic gradient of coastal shallow sediments and further on to evaluate the preferential deposition of microplastics in a given sediment grain fraction. Sediments from Marine Protected Areas (MPAs) contained the highest concentrations of microplastics (MPs): up to 0.90 +/- 0.10 MPs/g suggesting the transfer of microplastics from source areas to endpoint areas. In addition, a high proportion of microplastic filaments were found close to populated areas whereas fragment type microplastics were more common in MPAs. There was no clear trend between sediment grain size and microplastic deposition in sediments, although microplastics were always present in two grain size fractions: 2 mm > x > 1 mm and 1 mm > x 0.5 mm. PMID- 26803230 TI - Changes in disgust and heart rate during exposure for Obsessive Compulsive Disorder: A case series. AB - BACKGROUND AND OBJECTIVES: The emotion of disgust has been suggested as a factor contributing to a poor response to Cognitive Behaviour Therapy (CBT) in the treatment of Obsessive Compulsive Disorder (OCD). However, only limited information is available about the phenomenology of disgust in clinical OCD and the physiological mechanisms involved. This case series was designed to explore the phenomenology of OCD and the physiological activity associated with the emotion of disgust. METHODS: State disgust and heart rate was measured in eleven participants attending treatment for OCD during exposure relevant to their individual formulation. RESULTS: All participants with contamination and most patients with blood and injury related fears experienced a prominent increase in state disgust during exposure. These participants also had absent heart rate acceleration during exposure. Disgust response correlated with heart rate response (r = -0.63, p < 0.01) and Root Mean Square of Successive Differences (RMSSD) (r = 0.52, p < 0.01). LIMITATIONS: The design using ecologically valid stimuli and the limited number of participants did not allow between subject comparisons or more detailed analysis of relationship between trait and state disgust and between disgust and severity of OCD. CONCLUSIONS: Our findings show that a large proportion of our case series with OCD experience prominent disgust with signs of increased vagal tonus during their exposure. Such experiences differ from the concept of adrenergic activation used for psychoeducation in CBT and appraisals of harm and this may result in poorer therapeutic outcome. PMID- 26803231 TI - Selective attention in perfectionism: Dissociating valence from perfectionism relevance. AB - BACKGROUND AND OBJECTIVES: Maladaptive perfectionism has been identified as a predisposing and perpetuating factor for a range of disorders, including eating, anxiety, and mood disorders. An influential model of perfectionism, put forward by Shafran, Cooper, and Fairburn (2002), proposes that high perfectionism reflects an attentional bias that operates to afford greater attention to negative information than to positive information, when this information is perfectionism-relevant. The present study is the first to experimentally test this hypothesis.. METHOD: The present study assessed the type of stimuli that high perfectionists (n = 31) preferentially attend to compared to low perfectionists (n = 25) within a non-clinical population. Using an attentional probe task, we compared high and low perfectionist attentional responding to stimulus words that differed in terms of their emotional valence (positive vs. negative) and perfectionism-relevance (perfectionism-relevant vs. -irrelevant). RESULTS: Analysis revealed that, unlike low perfectionists, high perfectionists displayed greater attentional preference to negative than to positive information, but only for perfectionism-relevant stimuli.. LIMITATIONS: The implications must be considered within the limitations of the present study. The present study did not assess clinical participants, as such conclusions cannot be made regarding attentional bias that characterize clinical disorders in which perfectionism is identified as a predisposing and perpetuating factor. CONCLUSIONS: Theoretically, the attentional dot-probe task lends weight to the cognitive-behavioral model of clinical perfectionism, which proposed a biased attentional processing of negative perfectionism relevant stimuli within perfectionism. This conclusion was previously based on clinical impressions, whereas the present study used an objective performance measure. Clinically, therapists should take this attentional bias into account when planning treatments that involve targeting perfectionism.. PMID- 26803232 TI - Polyelectrolyte conformational transition in aqueous solvent mixture influenced by hydrophobic interactions and hydrogen bonding effects: PAA-water-ethanol. AB - Molecular dynamics simulations of poly(acrylic acid) PAA chain in water-ethanol mixture were performed for un-ionized and ionized cases at different degree-of ionization 0%, 80% and 100% of PAA chain by Na(+) counter-ions and co-solvent (ethanol) concentration in the range 0-90vol% ethanol. Aspects of structure and dynamics were investigated via atom pair correlation functions, number and relaxation of hydrogen bonds, nearest-neighbor coordination numbers, and dihedral angle distribution function for back-bone and side-groups of the chain. With increase in ethanol concentration, chain swelling is observed for un-ionized chain (f=0) and on the contrary chain shrinkage is observed for partially and fully ionized cases (i.e., f=0.8 and 1). For un-ionized PAA, with increase in ethanol fraction phieth the number of PAA-ethanol hydrogen bonds increases while PAA-water decreases. Increase in phieth leads to PAA chain expansion for un ionized case and chain shrinkage for ionized case, in agreement with experimental observations on this system. For ionized-PAA case, chain shrinkage is found to be influenced by intermolecular hydrogen bonding with water as well as ethanol. The localization of ethanol molecules near the un-ionized PAA backbone at higher levels of ethanol is facilitated by a displacement of water molecules indicating presence of specific ethanol hydration shell, as confirmed by results of the RDF curves and coordination number calculations. This behavior, controlled by hydrogen bonding provides a significant contribution to such a conformational transition behavior of the polyelectrolyte chain. The interactions between counter-ions and charges on the PAA chain also influence chain collapse. The underlying origins of polyelectrolyte chain collapse in water-alcohol mixtures are brought out for the first time via explicit MD simulations by this study. PMID- 26803234 TI - How to increase level of patients' awareness regarding the importance of statins despite the influence of the media? PMID- 26803233 TI - Telomere shortening and telomerase activity in ischaemic cardiomyopathy patients Potential markers of ventricular arrhythmia. AB - BACKGROUND: Implantable cardioverter defibrillators (ICDs) reduce mortality in patients with ischaemic cardiomyopathy at high risk of ventricular arrhythmias (VA). However, the current indication for ICD prescription needs improvement. Telomere and telomerase in leucocytes have been shown to associate with biological ageing and pathogenesis of cardiovascular diseases. We hypothesised that leucocyte telomere length, load-of-short telomeres and/or telomerase activity are associated with VA occurrence in ischaemic cardiomyopathy patients. METHODS AND RESULTS: 90 ischaemic cardiomyopathy patients with primary prevention ICDs were recruited. 35 had received appropriate therapy from the ICD for potentially-fatal VA while the remaining 55 patients had not. No significant differences in baseline demographic data relevant to telomere biology were seen between the two groups. There was no significant difference in the age and sex adjusted mean telomere length analysed by qPCR between the groups (p=0.88). In contrast, the load-of-short telomeres assessed by Universal-STELA method and telomerase activity by TRAP assay were both higher in patients who had appropriate ICD therapy and were significantly associated with incidence of ICD therapy (p=0.02, p=0.02). ROC analyses demonstrated that the sensitivity and specificity of these telomere dynamics in predicting potentially-fatal VA was higher than the current gold-standard - left ventricular ejection fraction (AUC 0.82 versus 0.47). CONCLUSION: The load-of-short telomeres and telomerase activity had a significant association with ICD therapy (for VA) in ischaemic cardiomyopathy patients. These biomarkers should be tested in prospective studies to assess their clinical utility in predicting VA after myocardial infarction and guiding primary prevention ICD prescription. PMID- 26803235 TI - Severe cardiomyopathy in a young patient with complete deficiency of adipose triglyceride lipase due to a novel mutation in PNPLA2 gene. PMID- 26803237 TI - Coronary fistula as an arteriovenous malformation behind the left atrium. Untightening the tangle with cardiac CT. PMID- 26803236 TI - Optimal duration of dual antiplatelet therapy after second-generation drug eluting stent implantation in patients with diabetes: The SECURITY (Second Generation Drug-Eluting Stent Implantation Followed By Six- Versus Twelve-Month Dual Antiplatelet Therapy)-diabetes substudy. AB - BACKGROUND/OBJECTIVES: The randomized SECURITY (Second-Generation Drug-Eluting Stent Implantation Followed by Six- Versus Twelve-Month Dual Antiplatelet Therapy) trial showed the non-inferiority of 6 vs. 12-month DAPT after percutaneous coronary intervention (PCI) with second-generation DES in a low-risk population. Nevertheless, diabetes mellitus (DM) remained a major predictor of adverse cardiovascular events. We aimed to assess the interaction between DAPT duration and outcome in DM patients. METHODS: All diabetic patients included in the SECURITY trial treated by second-generation DES PCI were analyzed. The primary endpoint was a composite of cardiac death, myocardial infarction (MI), stroke, definite or probable stent thrombosis (ST), or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at 12months. The main secondary endpoint was a composite of cardiac death, MI, stroke, definite or probable ST, or BARC type 2, 3, or 5 bleeding at 24months. RESULTS: Four hundred-twenty nine DM patients received either 6 (n=206) or 12 (n=223) months of DAPT. The primary endpoint occurred in 3.9% and 5.4% of patients in the 6 and 12-month DAPT group, respectively (log-rank test p=0.83). Similarly, no statistically significant difference in the secondary endpoint was observed between the two study groups (5.4% vs. 7.6%, p=0.620). Stent thrombosis rate was low irrespective of DAPT duration at both 12 (0.5% vs. 0.4%; p=0.804) and between 12 and 24months of follow-up (0.5% vs. 0%, p=0.291). At multivariable analysis, female gender (HR: 3.42; 95% CI 1.32-8.85; p=0.011 and HR 2.28; 95% CI 1.09-4.75; p=0.027) and insulin-treated diabetes mellitus (HR: 2.62; 95% CI 1.15-6.75; p=0.004 and HR: 2.23; 95% CI 1.09-6.33; p=0.003) were independent predictors of both primary and secondary endpoint. CONCLUSIONS: In diabetic patients treated by second generation DES PCI, we failed to find any additional benefit of prolonging DAPT beyond 6months, regardless of insulin-requiring status. PMID- 26803238 TI - Exercise as an adjuvant therapy against chronic atrial fibrillation. PMID- 26803239 TI - Vitamin D levels and depressive symptoms in patients with chronic heart failure. AB - BACKGROUND: Vitamin D (Vit D) is suggested to play a role in the regulation of physical function as well as in depression. Since, Vit D deficiency is common in patients with heart failure (HF), this study aims to explore if Vit D levels are associated with depressive symptoms and if this association is mediated by the patients' physical function. METHOD: 506 HF patients (mean age 71, 38% women) were investigated. Depressive symptoms and physical function were measured with the Centre for Epidemiological Studies Depression Scale and the physical function scale from the RAND-36. Vit D was measured in blood samples RESULTS: At baseline there was no relationship between depressive symptoms and Vit D levels. However, at 18months follow-up 29% of patients with Vit D <50nmol/l at baseline had depressive symptoms compared 19% of those with Vit D levels >50nmol/l (p<0.05). Only in patients with Vit D <50nmol/l, Vit D correlated significantly to physical function and depressive symptoms (r=.29, p<0.001 and r=.20, p<0.01). In structural equation modelling an indirect association between Vit D and depressive symptoms was found, mediated by physical function (B=0.20). This association was only found in patients with Vit D levels <50nmol/l. CONCLUSION: In HF patients with Vit D <50nmol/l, Vit D is associated to depressive symptoms during follow-up and this association is mediated by physical function. This relationship is not found in patients with Vitamin D level >50nmol/l. PMID- 26803240 TI - A brief report of Rhazes manuscripts in the field of cardiology and cardiovascular diseases. PMID- 26803241 TI - Transcatheter aortic valve implantation using the Lotus valve system in severe aortic stenosis in an orthotopic heart transplant patient. PMID- 26803242 TI - Lateral ST elevation as a practical electrocardiographic clue for apical aneurysm in hypertrophic cardiomyopathy patients. PMID- 26803243 TI - Healthy lifestyle factors and incident heart disease and mortality in candidates for primary prevention with statin therapy. AB - BACKGROUND: There are limited data on the use of healthy lifestyles among adults who are candidates for primary prevention of atherosclerotic cardiovascular disease (ASCVD) with statin therapy due to a 10-year predicted risk >=7.5%. We determined the prevalence of healthy lifestyle factors and their association with incident ASCVD and all-cause mortality in the Reason for Geographic and Racial Differences in Stroke study participants (n=5709). METHODS: Lifestyle factors (non-obese waist circumference, physical activity >=5 times-per-week, non smoking, low saturated-fat-intake, highest Mediterranean diet score quartile) were assessed during an in-home examination and interviewer-administered questionnaires. Adjudicated incident ASCVD (nonfatal/fatal stroke, nonfatal myocardial infarction or coronary heart disease death) and all-cause mortality were identified through active participant follow-up. RESULTS: Overall, 5.1%, 28.9%, 36.9%, 21.7% and 7.5% had 0, 1, 2, 3, and >=4 of the 5 healthy lifestyle factors studied. There were 377 incident ASCVD events (203 CHD events and 174 strokes) and 471 deaths during 5.8 and 6.0 median years of follow-up, respectively. ASCVD incidence rates (95% CI) per 1000-person-years associated with 0, 1, 2, 3 and >=4 healthy lifestyles were 13.4 (7.3-19.5), 12.8 (10.4 15.2), 11.0 (9.0-12.9), 11.0 (8.3-13.7), and 8.7 (4.9-12.4), respectively. Mortality rates associated with 0, 1, 2, 3 and >=4 healthy lifestyles were 20.6 (13.3-27.8), 15.9 (13.3-18.5), 13.1 (10.9-15.2), 12.6 (9.9-15.2) and 9.2 (5.3 13.2) per 1000-person-years, respectively. The use of more healthy lifestyles was associated with lower risks for ASCVD and mortality after multivariable adjustment. CONCLUSION: Healthy lifestyles are underutilized among high-risk US adults and may substantially reduce their ASCVD risk. PMID- 26803245 TI - Fractional flow reserve implementation in daily clinical practice: A European survey. PMID- 26803244 TI - Rapidly progressive infantile cardiomyopathy with mitochondrial respiratory chain complex V deficiency due to loss of ATPase 6 and 8 protein. PMID- 26803246 TI - FOLFOX chemotherapy as a cause of ventricular septal rupture after alcohol septal ablation for obstructive hypertrophic cardiomyopathy? PMID- 26803247 TI - Sub-acute transcatheter aortic valve implantation as bridge to recovery from cardio-pulmonary support following ST-elevation myocardial infarction and cardiogenic shock. PMID- 26803248 TI - Lung surfactant in chronic heart failure patients. PMID- 26803249 TI - Hernia of the diaphragmatic caval foramen causing right atrial "mass", caval obstruction and pulmonary embolism. PMID- 26803250 TI - Reversed takotsubo cardiomyopathy in a patient with new-onset multiple sclerosis: Cause, link, or just coincidence? PMID- 26803251 TI - Three parties, one direction: Research priorities in adults with congenital heart disease. What do professionals, patients and relatives want to know? AB - BACKGROUND: Patients, their relatives, as well as medical specialists from the fields of paediatric cardiology, cardiology and cardiac surgery were surveyed to investigate the current research needs in the field of congenital heart disease (CHD) focussing specifically on the needs of those affected. MATERIAL AND METHODS: An online survey including four groups of patients with CHD (Fontan circulation, transposition of the great arteries [TGA] after atrial switch [AS] and after arterial switch operation [ASO], tetralogy of Fallot [TOF]) was performed. Each questionnaire comprised twelve topics. Persons affected (patients and relatives) were surveyed by means of CHD group specific questionnaires. Participants were recruited through the German National Register for Congenital Heart Defects. RESULTS: N=596 affected persons (Fontan circulation: n=189; TGA after AS: n=64; TGA after ASO: n=90; TOF: n=253) and 75 physicians (57.3% paediatric cardiologists, 28.0% cardiologists, 10.7% cardiac surgeons, 4.0% other) participated. In general, those affected assume a greater need for research than physicians. Regarding the CHD related topics to be the focus of future research, those affected largely agreed with the participating physicians, although with a different ranking of research topics. CONCLUSIONS: Based on the results of our study the challenges immanent in routine care for the CHD patient groups investigated can be identified. Accordingly, these topics should be prioritized in the research of the coming years. PMID- 26803252 TI - The correlation between epsilon wave and coved-type ST-segment elevation in a patient with arrhythmogenic cardiomyopathy. PMID- 26803253 TI - Transcatheter deployment of two atrial septal defect closure devices using 3 dimensional transoesophageal echocardiography guidance. PMID- 26803254 TI - Tachycardiomyopathy: A case of dilated cardiomyopathy due to permanent junctional reentrant tachycardia. PMID- 26803255 TI - Erdheim-Chester disease as assessed by modern multimodality imaging. PMID- 26803256 TI - What difficulties do faculty members face when conducting workplace-based assessments in undergraduate clerkships? AB - OBJECTIVE: Workplace-based assessments are based on the principle of providing feedback to medical students on clinical performance in authentic settings. In practice, however, the assessment often overshadows the feedback. The aim of this study was to determine what problems faculty perceived when performing workplace based assessments and what solutions they suggested to overcome these difficulties. METHODS: Discussion meetings were conducted with education coordinators and faculty (n=55) from 11 peripheral hospitals concerning the difficulties encountered when conducting workplace-based assessments. We analysed the reports from these discussion meetings using an integrated approach guided by our research questions to code the data. Two researchers analysed the data independently and resolved differences of opinion through consensus. RESULTS: The problems perceived by faculty in workplace-based assessments (difficulties) and suggestions for improvement formed the overarching themes. Problems included the short duration of clerkships, students choosing the assessment moments, the use of grades for the mini-Clinical Evaluation Exercise, the difficulty in combining teacher and assessor roles and the difficulty in giving fail judgements. Suggestions for improvement included longer clerkship duration, faculty choosing the assessment moments, using a pass/fail system for the mini-Clinical Evaluation Exercise and forward feeding of performance from earlier clerkships following a fail judgement. CONCLUSIONS: Our study indicates that faculty perceive difficulties when conducting workplace-based assessments. These assessments need periodical review to understand the difficulties faculty experience using them; they also require periodical feedback to ensure their proper and effective use. PMID- 26803257 TI - CO2 capture using fly ash from coal fired power plant and applications of CO2 captured fly ash as a mineral admixture for concrete. AB - The utilization of fly ash as a solid sorbent material for CO2 capture via surface adsorption and carbonation reaction was evaluated as an economically feasible CO2 reduction technique. The results show that fly ash from a coal fired power plant can capture CO2 up to 304.7 MUmol/g fly ash, consisting of 2.9 and 301.8 MUmol/g fly ash via adsorption and carbonation, respectively. The CO2 adsorption conditions (temperature, pressure, and moisture) can affect CO2 capture performance of fly ash. The carbonation of CO2 with free CaO in fly ashes was evaluated and the results indicated that the reaction consumed most of free CaO in fly ash. The fly ashes after CO2 capture were further used for application as a mineral admixture for concrete. Properties such as water requirement, compressive strength, autoclave expansion, and carbonation depth of mortar and paste specimens using fly ash before and after CO2 capture were tested and compared with material standards. The results show that the expansion of mortar specimens using fly ash after CO2 capture was greatly reduced due to the reduction of free CaO content in the fly ash compared to the expansion of specimens using fresh fly ash. There were no significant differences in the water requirement and compressive strength of specimens using fly ash, before and after CO2 capture process. The results from this study can lead to an alternative CO2 capture technique with doubtless utilization of fly ash after CO2 capture as a mineral admixture for concrete. PMID- 26803258 TI - The influence of visitor use levels on visitor spatial behavior in off-trail areas of dispersed recreation use. AB - A variety of social and ecological factors influence the level and extent of ecological change that occurs in a park or protected area. Understanding these factors and how they are interrelated can help managers prevent undesirable ecological impacts, especially in areas without formal trails and visitor sites. This study examines the relationship between levels of visitor use and spatial patterns of visitor behavior at a variety of backcountry recreation destinations. Current assumptions in both the literature and simulation modeling efforts assume that visitor behavior either does not change with use level or that visitors are more likely to disperse at high levels of visitor use. Using visitor counts and GPS tracks of visitor behavior in locations where visitors could disperse off trail, we found that visitors' spatial behavior does vary with visitor use level in some recreation settings, however the patterns of visitor behavior observed in this study are sometimes contrary to current generalizations. When visitor behavior does vary with use level, visitors are dispersing more at low levels of visitor use not when use level is high. Overall, these findings suggest that in certain situations the amount of visitor use at a recreation destination may be a less important driver of ecological change than visitor behavior. PMID- 26803259 TI - Influence of nano-TiO2 particles on the bioaccumulation of Cd in soybean plants (Glycine max): A possible mechanism for the removal of Cd from the contaminated soil. AB - Phytoremediation is a highly efficient technique for the elimination of trace elements from contaminated soils through the shoots and roots of plants. This study was carried out to investigate the effects of nano-titanium dioxide (TiO2) on Cd uptake by soybean plants. The objective of the present research was to examine the potential to improve the phytoextraction of Cd by the application of nano-TiO2 particles. The results showed that an addition of Cd to the soil significantly decreased plant growth and the biomass, pigment and protein contents. Increases in the proline content and malondialdehyde (MDA) indicate that Cd toxicity stresses the plants. Fourier transform infrared spectroscopy (FTIR) was used to determine variations in functional groups due to the Cd taken up into the shoot and root tissues of plants. An application of nano-TiO2 particles restricts Cd toxicity by increasing the photosynthetic rate and growth parameters of the plants. The uptake of Cd was also increased from 128.5 to 507.6 MUg/plant with an increase in the nano-TiO2 concentration from 100 to 300 mg/kg in the soil. The application of nano-TiO2 significantly enhanced Cd uptake in the plants. The results of this study thus demonstrate that an application of nano TiO2 can increase Cd uptake and minimize Cd stress in soybean plants. PMID- 26803260 TI - Small scale temporal distribution of radiocesium in undisturbed coniferous forest soil: Radiocesium depth distribution profiles. AB - The depth distribution of pre-Fukushima and Fukushima-derived (137)Cs in undisturbed coniferous forest soil was investigated at four sampling dates from nine months to 18 months after the Fukushima nuclear power plant accident. The migration rate and short-term temporal variability among the sampling profiles were evaluated. Taking the time elapsed since the peak deposition of pre Fukushima (137)Cs and the median depth of the peaks, its downward displacement rates ranged from 0.15 to 0.67 mm yr(-1) with a mean of 0.46 +/- 0.25 mm yr(-1). On the other hand, in each examined profile considerable amount of the Fukushima derived (137)Cs was found in the organic layer (51%-92%). At this moment, the effect of time-distance on the downward distribution of Fukushima-derived (137)Cs seems invisible as its large portion is still found in layers where organic matter is maximal. This indicates that organic matter seems the primary and preferential sorbent of radiocesium that could be associated with the physical blockage of the exchanging sites by organic-rich dusts that act as a buffer against downward propagation of radiocesium, implying radiocesium to be remained in the root zone for considerable time period. As a result, this soil section can be a potential source of radiation dose largely due to high radiocesium concentration coupled with its low density. Generally, such kind of information will be useful to establish a dynamic safety-focused decision support system to ease and assist management actions. PMID- 26803262 TI - Influence of uncertainty inherent to heavy metal build-up and wash-off on stormwater quality. AB - Uncertainty inherent to heavy metal build-up and wash-off stems from process variability. This results in inaccurate interpretation of stormwater quality model predictions. The research study has characterised the variability in heavy metal build-up and wash-off processes based on the temporal variations in particle-bound heavy metals commonly found on urban roads. The study outcomes found that the distribution of Al, Cr, Mn, Fe, Ni, Cu, Zn, Cd and Pb were consistent over particle size fractions <150 MUm and >150 MUm, with most metals concentrated in the particle size fraction <150 MUm. When build-up and wash-off are considered as independent processes, the temporal variations in these processes in relation to the heavy metals load are consistent with variations in the particulate load. However, the temporal variations in the load in build-up and wash-off of heavy metals and particulates are not consistent for consecutive build-up and wash-off events that occur on a continuous timeline. These inconsistencies are attributed to interactions between heavy metals and particulates <150 MUm and >150 MUm, which are influenced by particle characteristics such as organic matter content. The behavioural variability of particles determines the variations in the heavy metals load entrained in stormwater runoff. Accordingly, the variability in build-up and wash-off of particle-bound pollutants needs to be characterised in the description of pollutant attachment to particulates in stormwater quality modelling. This will ensure the accounting of process uncertainty, and thereby enhancing the interpretation of the outcomes derived from modelling studies. PMID- 26803261 TI - Forward osmosis filtration for removal of organic foulants: Effects of combined tannic and alginic acids. AB - The filtration performance of combined organic foulants by forward osmosis (FO) in active-layer-facing-the-draw-solution (AL-facing-DS) orientation was investigated systematically. Tannic acid and alginate were used as model organic foulants for polysaccharides and humic dissolved organic matters, respectively. The FO could reject combined and single tannic acid and alginate foulants effectively. The more severe fouling flux decline, accompanied with lower combined foulants' retention, was observed with increasing proportions of tannic acid in the combined foulants-containing feed, which was ascribed mainly to the more severe fouling resulting from tannic acid adsorption within the porous support layer of the FO membrane compared to minor alginate deposition on the membrane surface. It was found that the higher the initial flux level and cross flow velocity, the faster the flux decline with lower mixed foulants retention. It was also revealed that the calcium ions in a basic solution enhanced the combined fouling flux reduction and combined foulants retention. As the major constituent of the combined fouling layer, the adsorption of tannic acid might play a more significant role in the mixed fouling of the FO membrane, which was probably influenced by permeation drag caused by water flux and chemical interactions induced by feed solution pH and calcium ion concentration. PMID- 26803263 TI - Influence of hydraulic retention time on indigenous microalgae and activated sludge process. AB - Integration of the microalgae and activated sludge (MAAS) process in municipal wastewater treatment and biogas production from recovered MAAS was investigated by studying the hydraulic retention time (HRT) of semi-continuous photo bioreactors. An average total nitrogen (TN) removal efficiency (RE) of maximum 81.5 +/- 5.1 and 64.6 +/- 16.2% was achieved at 6 and 4 days HRT. RE of total phosphorous (TP) increased slightly at 6 days (80 +/- 12%) HRT and stabilized at 4 days (56 +/- 5%) and 2 days (55.5 +/- 5.5%) HRT due to the fluctuations in COD and N/P mass ratio of the periodic wastewater. COD and organic carbon were removed efficiently and a rapidly settleable MAAS with a sludge volume index (SVI_10) of less than 117 mL g(-1) was observed at all HRTs. The anaerobic digestion of the untreated MAAS showed a higher biogas yield of 349 +/- 10 mL g VS(-1) with 2 days HRT due to a low solids retention time (SRT). Thermal pretreatment of the MAAS (120 degrees C, 120 min) did not show any improvement with biogas production at 6 days (269 +/- 3 (untreated) and 266 +/- 16 (treated) mL gVS(-1)), 4 days (258 +/- 11(untreated) and 263 +/- 10 (treated) mL gVS(-1)) and 2 days (308 +/- 19 mL (treated) gVS(-1)) HRT. Hence, the biogas potential tests showed that the untreated MAAS was a feasible substrate for biogas production. Results from this proof of concept support the application of MAAS in wastewater treatment for Swedish conditions to reduce aeration, precipitation chemicals and CO2 emissions. PMID- 26803264 TI - Low pressure UV/H2O2 treatment for the degradation of the pesticides metaldehyde, clopyralid and mecoprop - Kinetics and reaction product formation. AB - The degradation kinetics of three pesticides - metaldehyde, clopyralid and mecoprop - by ultraviolet photolysis and hydroxyl radical oxidation by low pressure ultraviolet hydrogen peroxide (LP-UV/H2O2) advanced oxidation was determined. Mecoprop was susceptible to both LP-UV photolysis and hydroxyl radical oxidation, and exhibited the fastest degradation kinetics, achieving 99.6% (2.4-log) degradation with a UV fluence of 800 mJ/cm(2) and 5 mg/L hydrogen peroxide. Metaldehyde was poorly degraded by LP-UV photolysis while 97.7% (1.6 log) degradation was achieved with LP-UV/H2O2 treatment at the maximum tested UV fluence of 1000 mJ/cm(2) and 15 mg/L hydrogen peroxide. Clopyralid was hardly susceptible to LP-UV photolysis and exhibited the lowest degradation by LP UV/H2O2 among the three pesticides. The second-order reaction rate constants for the reactions between the pesticides and OH-radicals were calculated applying a kinetic model for LP-UV/H2O2 treatment to be 3.6 * 10(8), 2.0 * 10(8) and 1.1 * 10(9) M(-1) s(-1) for metaldehyde, clopyralid and mecoprop, respectively. The main LP-UV photolysis reaction product from mecoprop was 2-(4-hydroxy-2 methylphenoxy) propanoic acid, while photo-oxidation by LP-UV/H2O2 treatment formed several oxidation products. The photo-oxidation of clopyralid involved either hydroxylation or dechlorination of the ring, while metaldehyde underwent hydroxylation and produced acetic acid as a major end product. Based on the findings, degradation pathways for the three pesticides by LP-UV/H2O2 treatment were proposed. PMID- 26803265 TI - Contrasting regional and national mechanisms for predicting elevated arsenic in private wells across the United States using classification and regression trees. AB - Arsenic contamination in groundwater is a public health and environmental concern in the United States (U.S.) particularly where monitoring is not required under the Safe Water Drinking Act. Previous studies suggest the influence of regional mechanisms for arsenic mobilization into groundwater; however, no study has examined how influencing parameters change at a continental scale spanning multiple regions. We herein examine covariates for groundwater in the western, central and eastern U.S. regions representing mechanisms associated with arsenic concentrations exceeding the U.S. Environmental Protection Agency maximum contamination level (MCL) of 10 parts per billion (ppb). Statistically significant covariates were identified via classification and regression tree (CART) analysis, and included hydrometeorological and groundwater chemical parameters. The CART analyses were performed at two scales: national and regional; for which three physiographic regions located in the western (Payette Section and the Snake River Plain), central (Osage Plains of the Central Lowlands), and eastern (Embayed Section of the Coastal Plains) U.S. were examined. Validity of each of the three regional CART models was indicated by values >85% for the area under the receiver-operating characteristic curve. Aridity (precipitation minus potential evapotranspiration) was identified as the primary covariate associated with elevated arsenic at the national scale. At the regional scale, aridity and pH were the major covariates in the arid to semi-arid (western) region; whereas dissolved iron (taken to represent chemically reducing conditions) and pH were major covariates in the temperate (eastern) region, although additional important covariates emerged, including elevated phosphate. Analysis in the central U.S. region indicated that elevated arsenic concentrations were driven by a mixture of those observed in the western and eastern regions. PMID- 26803266 TI - Innovative sponge-based moving bed-osmotic membrane bioreactor hybrid system using a new class of draw solution for municipal wastewater treatment. AB - For the first time, an innovative concept of combining sponge-based moving bed (SMB) and an osmotic membrane bioreactor (OsMBR), known as the SMB-OsMBR hybrid system, were investigated using Triton X-114 surfactant coupled with MgCl2 salt as the draw solution. Compared to traditional activated sludge OsMBR, the SMB OsMBR system was able to remove more nutrients due to the thick-biofilm layer on sponge carriers. Subsequently less membrane fouling was observed during the wastewater treatment process. A water flux of 11.38 L/(m(2) h) and a negligible reverse salt flux were documented when deionized water served as the feed solution and a mixture of 1.5 M MgCl2 and 1.5 mM Triton X-114 was used as the draw solution. The SMB-OsMBR hybrid system indicated that a stable water flux of 10.5 L/(m(2) h) and low salt accumulation were achieved in a 90-day operation. Moreover, the nutrient removal efficiency of the proposed system was close to 100%, confirming the effectiveness of simultaneous nitrification and denitrification in the biofilm layer on sponge carriers. The overall performance of the SMB-OsMBR hybrid system using MgCl2 coupled with Triton X-114 as the draw solution demonstrates its potential application in wastewater treatment. PMID- 26803267 TI - Geostatistical analysis of tritium, groundwater age and other noble gas derived parameters in California. AB - Key characteristics of California groundwater systems related to aquifer vulnerability, sustainability, recharge locations and mechanisms, and anthropogenic impact on recharge are revealed in a spatial geostatistical analysis of a unique data set of tritium, noble gases and other isotopic analyses unprecedented in size at nearly 4000 samples. The correlation length of key groundwater residence time parameters varies between tens of kilometers ((3)H; age) to the order of a hundred kilometers ((4)Heter; (14)C; (3)Hetrit). The correlation length of parameters related to climate, topography and atmospheric processes is on the order of several hundred kilometers (recharge temperature; delta(18)O). Young groundwater ages that highlight regional recharge areas are located in the eastern San Joaquin Valley, in the southern Santa Clara Valley Basin, in the upper LA basin and along unlined canals carrying Colorado River water, showing that much of the recent recharge in central and southern California is dominated by river recharge and managed aquifer recharge. Modern groundwater is found in wells with the top open intervals below 60 m depth in the southeastern San Joaquin Valley, Santa Clara Valley and Los Angeles basin, as the result of intensive pumping and/or managed aquifer recharge operations. PMID- 26803268 TI - Reduction in horizontal transfer of conjugative plasmid by UV irradiation and low level chlorination. AB - The widespread presence of antibiotic resistance genes (ARGs) and antibiotic resistant bacteria (ARB) in the drinking water system facilitates their horizontal gene transfer among microbiota. In this study, the conjugative gene transfer of RP4 plasmid after disinfection including ultraviolet (UV) irradiation and low-level chlorine treatment was investigated. It was found that both UV irradiation and low-level chlorine treatment reduced the conjugative gene transfer frequency. The transfer frequency gradually decreased from 2.75 * 10(-3) to 2.44 * 10(-5) after exposure to UV doses ranging from 5 to 20 mJ/cm(2). With higher UV dose of 50 and 100 mJ/cm(2), the transfer frequency was reduced to 1.77 * 10(-6) and 2.44 * 10(-8). The RP4 plasmid transfer frequency was not significantly affected by chlorine treatment at dosages ranging from 0.05 to 0.2 mg/l, but treatment with 0.3-0.5 mg/l chlorine induced a decrease in conjugative transfer to 4.40 * 10(-5) or below the detection limit. The mechanisms underlying these phenomena were also explored, and the results demonstrated that UV irradiation and chlorine treatment (0.3 and 0.5 mg/l) significantly reduced the viability of bacteria, thereby lowering the conjugative transfer frequency. Although the lower chlorine concentrations tested (0.05-0.2 mg/l) were not sufficient to damage the cells, exposure to these concentrations may still depress the expression of a flagellar gene (FlgC), an outer membrane porin gene (ompF), and a DNA transport-related gene (TraG). Additionally, fewer pili were scattered on the bacteria after chlorine treatment. These findings are important in assessing and controlling the risk of ARG transfer and dissemination in the drinking water system. PMID- 26803269 TI - Characterization of antimicrobial lipopeptides produced by Bacillus sp. LM7 isolated from chungkookjang, a Korean traditional fermented soybean food. AB - A wild-type microorganism exhibiting antimicrobial activities was isolated from the Korean traditional fermented soybean food Chungkookjang and identified as Bacillus sp. LM7. During its stationary growth phase, the microorganism secreted an antimicrobial substance, which we partially purified using a simple two-step procedure involving ammonium sulfate precipitation and heat treatment. The partially purified antimicrobial substance, Anti-LM7, was stable over a broad pH range (4.0-9.0) and at temperatures up to 80 degrees C for 30 min, and was resistant to most proteolytic enzymes and maintained its activity in 30% (v/v) organic solvents. Anti-LM7 inhibited the growth of a broad range of Gram-positive bacteria, including Bacillus cereus and Listeria monocytogenes, but it did not inhibit lactic acid bacteria such as Lactobacillus plantarum and Lactococcus lactis subsp. Lactis. Moreover, unlike commercially available nisin and polymyxin B, Anti-LM7 inhibited certain fungal strains. Lastly, liquid chromatography-mass spectrometry analysis of Anti-LM7 revealed that it contained eight lipopeptides belonging to two families: four bacillomycin D and four surfactin analogs. These Bacillus sp. LM7-produced heterogeneous lipopeptides exhibiting extremely high stability and a broad antimicrobial spectrum are likely to be closely related to the antimicrobial activity of Chungkookjang, and their identification presents an opportunity for application of the peptides in environmental bioremediation, pharmaceutical, cosmetic, and food industries. PMID- 26803270 TI - Prospecting for the incidence of genes involved in ochratoxin and fumonisin biosynthesis in Brazilian strains of Aspergillus niger and Aspergillus welwitschiae. AB - Aspergillus niger "aggregate" is an informal taxonomic rank that represents a group of species from the section Nigri. Among A. niger "aggregate" species Aspergillus niger sensu stricto and its cryptic species Aspergillus welwitschiae (=Aspergillus awamori sensu Perrone) are proven as ochratoxin A and fumonisin B2 producing species. A. niger has been frequently found in tropical and subtropical foods. A. welwitschiae is a new species, which was recently dismembered from the A. niger taxon. These species are morphologically very similar and molecular data are indispensable for their identification. A total of 175 Brazilian isolates previously identified as A. niger collected from dried fruits, Brazil nuts, coffee beans, grapes, cocoa and onions were investigated in this study. Based on partial calmodulin gene sequences about one-half of our isolates were identified as A. welwitschiae. This new species was the predominant species in onions analyzed in Brazil. A. niger and A. welwitschiae differ in their ability to produce ochratoxin A and fumonisin B2. Among A. niger isolates, approximately 32% were OTA producers, but in contrast only 1% of the A. welwitschiae isolates revealed the ability to produce ochratoxin A. Regarding fumonisin B2 production, there was a higher frequency of FB2 producing isolates in A. niger (74%) compared to A. welwitschiae (34%). Because not all A. niger and A. welwitschiae strains produce ochratoxin A and fumonisin B2, in this study a multiplex PCR was developed for detecting the presence of essential genes involved in ochratoxin (polyketide synthase and radHflavin-dependent halogenase) and fumonisin (alpha oxoamine synthase) biosynthesis in the genome of A. niger and A. welwitschiae isolates. The frequency of strains harboring the mycotoxin genes was markedly different between A. niger and A. welwitschiae. All OTA producing isolates of A. niger and A. welwitschiae showed in their genome the pks and radH genes, and 95.2% of the nonproducing isolates did not contain these genes. The alpha oxoamine synthase gene was detected in 100% and 36% of the A. niger and A. welwitschiae isolates, respectively. The loss of ochratoxin A production in A. niger and A. welwitschiae is highly associated with gene deletions within the ochratoxin biosynthetic gene cluster. The loss of fumonisin production in A. welwitschiae is associated with gene deletions within the fumonisin biosynthetic gene cluster, but this is not the case with A. niger. PMID- 26803271 TI - Draft genome sequence and chemical profiling of Fusarium langsethiae, an emerging producer of type A trichothecenes. AB - Fusarium langsethiae is a widespread pathogen of small grain cereals, causing problems with T-2 and HT-2 toxin contamination in grains every year. In an effort to better understand the biology of this fungus, we present a draft genome sequence of F. langsethiae Fl201059 isolated from oats in Norway. The assembly was fragmented, but reveals a genome of approximately 37.5 Mb, with a GC content around 48%, and 12,232 predicted protein-coding genes. Focusing on secondary metabolism we identified candidate genes for 12 polyketide synthases, 13 non ribosomal peptide synthetases, and 22 genes for terpene/isoprenoid biosynthesis. Some of these were found to be unique compared to sequence databases. The identified putative Tri5 cluster was highly syntenic to the cluster reported in F. sporotrichioides. Fusarium langsethiae Fl201059 produces a high number of secondary metabolites on Yeast Extract Sucrose (YES) agar medium, dominated by type A trichothecenes. Interestingly we found production of glucosylated HT-2 toxin (Glu-HT-2), previously suggested to be formed by the host plant and not by the fungus itself. In greenhouse inoculations of F. langsethiae Fl201059 on barley and oats, we detected the type A trichothecenes: neosolaniol, HT-2 toxin, T-2 toxin, Glu-HT-2 and numerous derivatives of these. PMID- 26803272 TI - The response of foodborne pathogens to osmotic and desiccation stresses in the food chain. AB - In combination with other strategies, hyperosmolarity and desiccation are frequently used by the food processing industry as a means to prevent bacterial proliferation, and particularly that of foodborne pathogens, in food products. However, it is increasingly observed that bacteria, including human pathogens, encode mechanisms to survive and withstand these stresses. This review provides an overview of the mechanisms employed by Salmonella spp., Shiga toxin producing E. coli, Cronobacter spp., Listeria monocytogenes and Campylobacter spp. to tolerate osmotic and desiccation stresses and identifies gaps in knowledge which need to be addressed to ensure the safety of low water activity and desiccated food products. PMID- 26803273 TI - In vitro anticancer potential of BaCO3 nanoparticles synthesized via green route. AB - Green synthesis of nanoparticles is a growing research area because of their potential applications in nanomedicine. Barium carbonate nanoparticles (BaCO3 NPs) were synthesized using an aqueous extract of Mangifera indica seed as a reducing agent. These particles were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Transmission electron microscopy (TEM), selected area electron diffraction (SAED), Energy-dispersive-X-ray (EDX) and X-ray photoelectron spectroscopy (XPS) analysis. HR-TEM images are confirmed that green synthesized BaCO3 NPs have spherical, triangular and uneven shapes. EDX analysis confirmed the presence of Ba, C and O. The peaks at 2theta of 19.45, 23.90, 24.29, 27.72, 33.71, 34.08, 34.60, 41.98, 42.95, 44.18, 44.85, and 46.78 corresponding to (110), (111), (021), (002), (200), (112), (130), (221), (041), (202), (132) and (113) showed that BaCO3 NPs average size was ~18.3 nm. SAED pattern confirmed that BaCO3 NPs are crystalline nature. BaCO3 NPs significantly inhibited cervical carcinoma cells, as evidenced by cytotoxicity assay. Immunofluorescence and fluorescence assays showed that BaCO3 NPs increased the expression and activity of caspase-3, an autocatalytic enzyme that promotes apoptosis. According to the results, green synthesis route has great potential for easy, rapid, inexpensive, eco-friendly and efficient development of novel multifunctional nanoparticles for the treatment of cancer. PMID- 26803274 TI - Trace metal ions in hair from frequent hair dyers in China and the associated effects on photo-oxidative damage. AB - Human hairs are subject to oxidative modification when exposed to sunlight. In the present study, samples of human hair from Chinese volunteers that included frequent hair dyers and non-dyers were analyzed for metal ions such as iron, copper, magnesium, aluminum, zinc and lead. The generation of hydroxyl radicals during UVA (315-400 nm) photoageing was quantified and oxidative damages characterized by proteomic and SEM analysis. It was concluded that high levels of metal ions, particularly those derived from iron and copper, identified in the dyed hairs are associated with enhanced photoformation of hydroxyl radicals and resultant photooxidative damage of the hair. Reactive oxygen species, including hydroxyl radicals, generated via an electron transfer mechanism with hair photosensitizers react with hair proteins. Proteomic analysis of hair samples from frequent hair dyers, regardless of age and gender, showed an almost 1.6 fold increase in the protein oxidative modification levels compared to the undyed samples. As a result, a more pronounced physical damage including fragmentation and cross-linkage of cuticle scales was observed on the surface of dyed hair samples during the photoageing. This work is aimed at better understanding the role of metal ions in dyed hairs and their possible role in photosensitizing hair proteins. The results from this study are anticipated to contribute to the improved development of hair coloring cosmetics and hair care products. PMID- 26803275 TI - Determination of UV action spectra affecting the infection process of Oidium neolycopersici, the cause of tomato powdery mildew. AB - Oidium neolycopersici, the cause of powdery mildew in tomato, was exposed to UV radiation from 250 to 400 nm for 1, 12, or 24 min. Radiation <= 280 nm strongly reduced conidial germination, hyphal expansion, penetration attempt and infection of O. neolycopersici. From 290 to 310 nm the effect depended on duration of exposure, while there was no effect >= 310 nm. There were no significant differences within the effective UV range (250-280 nm). Conidial germination on a water agar surface was <20% or around 40%, respectively, if samples were exposed for 1 min within the effective UV range followed by 24h or 48 h incubation. Twelve or 24 min exposure reduced germination to close to nil. A similar trend occurred for germination of conidia on leaf disks on water agar in Petri dishes. The effective UV range significantly reduced all subsequent developmental stages of O. neolycopersici. There was no cytoplasmic mitochondrial streaming in conidia exposed to the effective UV range, indicating that there may be a direct effect via cell cycle arrest. There was no indication of reactive oxygen species involvement in UV mediated inhibition of O. neolycopersici. Optical properties of O. neolycopersici indicated that the relative absorption of UV was high within the range of 250 to 320 nm, and very low within the range of 340 to 400 nm. Identification of UV wavelengths effective against O. neolycopersici provides a future basis for precise disease control. PMID- 26803276 TI - Sudden gains in Cognitive Therapy and Interpersonal Psychotherapy for adult depression. AB - OBJECTIVE: We examined the rates, baseline predictors and clinical impact of sudden gains in a randomized comparison of individual Cognitive Therapy (CT) and Interpersonal Psychotherapy (IPT) for adult depression. METHOD: 117 depressed outpatients received 16-20 sessions of either CT or IPT. Session-by-session symptom severity was assessed using the BDI-II. Sudden gains were examined using the original criteria as defined by Tang and DeRubeis (1999b). Furthermore, we examined whether the duration of the between-session interval at which sudden gains were recorded affected the results. RESULTS: There were significantly more patients with sudden gains in CT (42.2%) as compared to IPT (24.5%). The difference appeared to be driven by the criterion representing the stability of the gain. No between-group differences were found with regard to the magnitude, timing and predictors of the gains. Those with sudden gains were less depressed at post-treatment and follow-up. After controlling for the duration of the between-session interval, the difference in rates between the two conditions became a non-significant trend. Other sudden gains characteristics were similar to those observed when allowing for longer intervals as well. CONCLUSIONS: The current study indicates differences in occurrence of sudden gains in two treatment modalities that overall showed similar results, which might reflect different mechanisms of change. PMID- 26803278 TI - CFTR modulation for young children with cystic fibrosis. PMID- 26803277 TI - Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study. AB - BACKGROUND: Ivacaftor has been shown to be a safe, effective treatment for cystic fibrosis in patients aged 6 years or older with a CFTR gating mutation. We aimed to assess the safety, pharmacokinetics, and pharmacodynamics of ivacaftor in children aged 2-5 years. METHODS: In the two-part KIWI study, we enrolled children aged 2-5 years weighing 8 kg or more with a confirmed diagnosis of cystic fibrosis and a CFTR gating mutation on at least one allele from 15 hospitals in the USA, UK, and Canada. Participants received oral ivacaftor 50 mg (if bodyweight <14 kg) or 75 mg (if bodyweight >=14 kg) every 12 h for 4 days in part A (to establish the short-term safety of doses for subsequent assessment in part B), and then for 24 weeks in part B (to assess safety and longer-term pharmacodynamics). Children could participate in both or just one part of the study. Primary outcomes were pharmacokinetics and safety, analysed in all patients who received at least one dose of ivacaftor. Secondary outcomes were absolute change from baseline in sweat chloride concentrations and bodyweight, body-mass index (BMI), and height Z scores, and pharmacokinetic parameter estimation of ivacaftor. This study is registered with ClinicalTrials.gov, number NCT01705145. FINDINGS: Between Jan 8, 2013, and March 1, 2013, nine patients were enrolled onto part A of the study, all of whom completed the 4 day treatment period, and eight of whom took part in part B. Between June 28, 2013, and Sept 26, 2013, 34 patients were enrolled in part B, 33 of whom completed the 24 week treatment period. All patients received at least one dose of ivacaftor. Results of ivacaftor pharmacokinetics suggested that exposure was similar to that reported in adults (median Cmin were 536 ng/mL for the 50 mg dose; 580 ng/mL for the 75 mg dose; median ivacaftor AUC values were 9840 ng * h/mL and 10 200 ng * h/mL, respectively). Common adverse events in part B included cough (in 19 [56%] of 34 patients) and vomiting (in ten [29%]). Five (15%) patients had liver function test (LFT) results that were more than eight times higher than the upper limit of normal, four of whom had study drug interrupted, and one of whom had study drug discontinued. Six (18%) of 34 patients had seven serious adverse events; a raised concentration of transaminases was the only serious adverse event regarded as related to ivacaftor and the only adverse event that resulted in study treatment discontinuation. At week 24, in patients for whom we had data, sweat chloride had changed from baseline by a mean of -46.9 mmol/L (SD 26.2, p<0.0001), weight Z score by 0.2 (0.3; p<0.0001), BMI Z score by 0.4 (0.4, p<0.0001), and height Z score by -0.01 (0.3; p=0.84). INTERPRETATION: Ivacaftor at doses of 50 mg and 75 mg seems to be safe in children aged 2-5 years with cystic fibrosis with a gating mutation followed up for 24 weeks, although the frequency of elevated LFTs suggests that monitoring should be frequent in young children, particularly those with a history of elevated LFTs. Results of an ongoing extension study assessing durability of these effects and longer-term safety are warranted. FUNDING: Vertex Pharmaceuticals Incorporated. PMID- 26803279 TI - Cystic fibrosis: a call for research papers. PMID- 26803280 TI - Effects of antiepileptic drug on thyroid hormones in patients with epilepsy: A meta-analysis. AB - PURPOSE: As antiepileptic drugs (AEDs) are known to be associated with alterations in thyroid profiles, we aimed to carry out a meta-analysis to comprehensively assess the effects of AEDs on thyroid hormones in patients with epilepsy. METHODS: We searched the NCBI (PubMed), ISI Web of Science, EMBASE databases, and Cochrane Library to identify studies evaluating the association between AED use and thyroid hormone profiles in patients with epilepsy. Fixed or random effects meta-analysis was used to pool results across studies. RESULTS: In all, 35 studies were included in our analysis. Out of a total of 997 patients in these studies, epileptic patients receiving AEDs showed an overall significant decrease in thyroxin (T4) and free T4 (fT4) and higher levels of thyroid stimulating hormone (TSH) than the controls (T4: standardized mean difference [SMD]=-1.839, 95% confidence interval [CI], -2.063 to -1.614; fT4: SMD=-1.190, 95% CI, -1.687 to -0.692; TSH: SMD=0.445, 95% CI, 0.031-0.858). Notably, the use of carbamazepine (CBZ) suggested a significant decrease in triiodothyronine (T3), T4, and fT4; phenytoin (PHT) use showed a decrease in T4 and fT4; and valproic acid (VPA) use was associated with decreased T4 and increased TSH. CONCLUSION: Our study suggests that use of AEDs such as CBZ, PHT, and VPA, was associated with alteration of thyroid hormones among patients with epilepsy. PMID- 26803282 TI - Epileptic spasms in clusters with focal EEG paroxysms: A study of 12 patients. AB - OBJECTIVE: We analyzed the electroclinical features, etiology, treatment, and outcome of 12 patients with West syndrome (WS) associated with focal hypsarrhythmia (FH). METHODS: Between February 2005 and July 2013, 12 patients met the electroclinical diagnostic criteria of WS associated with FH. Hypsarrhythmia was considered to be focal when two or three brain lobes were involved. Patients with hemihypsarrhythmia were excluded. RESULTS: All patients had epileptic spasms (ES) in clusters of a structural etiology. Four had a porencephalic cyst, two had focal cortical dysplasia, two had open-lip schizencephaly, and one each had unilateral polymicrogyria, shunted hydrocephalus, glioma, and cerebral hemiatrophy. Age at ES onset was between 2 and 8 months, with a mean age of 5 and a median age of 6 months. Seven patients had asymmetric ES, three had symmetric ES, and two patients had unilateral ES. FH was seen over the posterior regions in nine and over the anterior regions in three. Ictal EEG recordings showed diffuse high-amplitude slow waves in six patients, diffuse slow waves followed by voltage attenuation in three, and diffuse fast rhythms in three others. In three patients the ictal paroxysms were unilateral. Six patients responded well to surgery. CONCLUSION: ES associated with FH are secondary to structural lesions. Surgery should be considered earlier in the management of this group of patients. PMID- 26803281 TI - Use of dietary therapies amongst patients with GLUT1 deficiency syndrome. AB - PURPOSE: GLUT-1 deficiency syndrome (GLUT1DS) is a neurologic disorder manifesting as epilepsy, abnormal movements, and cognitive delay. The currently accepted treatment of choice is the classic 4:1 ratio ketogenic diet. METHODS: A 2-page survey was distributed to all attendees of a family-centered conference for GLUT1DS in July 2015. The surveys were completed by parents, collected anonymously, and information analyzed in a database. RESULTS: Surveys were received from 92 families, of which 90 (98%) had been treated with dietary therapies. Diets used were extremely varied: 59 were treated with the classic ketogenic diet (KD), 29 with the Modified Atkins Diet (MAD), 4 with the Medium chain Triglyceride (MCT) Diet and 2 with the low glycemic index treatment. The mean diet duration was 5.5 years (range: 1 month-20 years). Of those with seizures, 95% of the children had >50% seizure reduction and 80% had >90% seizure reduction. Children who were seizure-free were currently younger on average (8.2 vs. 11.6 years, p=0.01) and slightly younger at GLUT1DS diagnosis (3.8 vs. 5.3 years, p=0.05). There was an equal percentage of children seizure-free receiving the KD/MCT Diets compared to the MAD/Low Glycemic Index Treatment (74% vs. 63%, p=0.30). The majority (64%) were not receiving anticonvulsants. CONCLUSION: This represents the largest series of KD experience in children with GLUT1DS. Nearly all patients surveyed were on dietary therapies for long durations with reported excellent seizure control, often without anticonvulsant drugs. Several different ketogenic diets were utilized with similar efficacy. Early diagnosis and treatment were correlated with success. PMID- 26803283 TI - Prevalence of active convulsive epilepsy in an urban slum in Enugu South East Nigeria. AB - PURPOSE: To determine the prevalence of active convulsive epilepsy and treatment gap in two Urban slums in Enugu South East Nigeria. METHODS: A 3 phase cross sectional descriptive study was done to survey individuals >= 15 years in 2 slums in Enugu, South East Nigeria. RESULTS: The prevalence of epilepsy was 6.0 (95% CI: 5.9-6.0) per 1000 (men 4.4/1000, 95% CI: 2.3-6.4, women 7.8/1000, 95% CI: 4.9 10.4), p=0.06. The peak age of active convulsive epilepsy was 40-44 years (11.2 per 1000) with two smaller peaks at 25-29 and >= 50 years. The age and sex adjusted prevalence using WHO standard population and 2006 Nigerian census population were 5.9 per 1000 (95% CI: 4.0-7.9) and 5.4 per 1000 (95% CI: 3.4 7.4). CONCLUSION: The prevalence of epilepsy is high in urban slums in Enugu. Nationwide studies should be done to find out the true prevalence in the country. PMID- 26803285 TI - Diverse sapovirus genotypes identified in children hospitalised with gastroenteritis in selected regions of South Africa. AB - BACKGROUND: Sapoviruses (SaVs) are recognised as causative agents of gastroenteritis worldwide. However, data on the genetic diversity of this virus in Africa are lacking, particularly in the form of current long-term studies. OBJECTIVE: To determine the genetic diversity of SaVs in children hospitalised with gastroenteritis in South Africa (SA). STUDY DESIGN: From April 2009 to December 2013, SaVs were characterised from stool specimens from children hospitalised with gastroenteritis in four provinces of SA. RESULTS: Fourteen different SaV genotypes were identified from the 221 strains that were characterised. Genogroup (G) IV predominated overall and was detected in 24% (53/221) of specimens. The other identified genotypes included six belonging to GI (GI.1-GI.3, GI.5, GI.6, and GI.7) and seven belonging to GII (GII.1-GII.7). CONCLUSION: This study has provided the first comprehensive data on the genetic diversity of SaVs in a clinical setting in SA, contributing to the global knowledge of this virus. PMID- 26803284 TI - Visualizing microtubule structural transitions and interactions with associated proteins. AB - Microtubules (MTs) have been the subject of cryo-electron microscopy (cryo-EM) studies since the birth of this technique. Although MTs pose some unique challenges, having to do with the presence of a MT seam, lattice variability and disorder, MT cryo-EM reconstructions are steadily improving in resolution and providing exciting new insights into MT structure and function. Recent work has lead to the atomic-detail visualization of lateral contacts between tubulin subunits and the conformational changes that give rise to strain in the MT lattice accompanying GTP hydrolysis. Cryo-EM has also been invaluable in describing the interactions between MTs and MT associated proteins (MAPs), which function to regulate MT dynamic instability, move cargoes, or contribute to other MT cellular processes. PMID- 26803287 TI - Emerging roles of RNA modifications in bacteria. AB - RNA modifications are known to abound in stable tRNA and rRNA, where they cluster around functionally important regions. However, RNA-seq based techniques profiling entire transcriptomes are now uncovering an abundance of modified ribonucleotides in mRNAs and noncoding RNAs, too. While most of the recent progress in understanding the regulatory influence of these new RNA modifications stems from eukaryotes, there is growing evidence in bacteria for modified nucleotides beyond the stable RNA species, including modifications of small regulatory RNAs. Given their small genome size, good genetic tractability, and ample knowledge of modification enzymes, bacteria offer excellent model systems to decipher cellular functions of RNA modifications in many diverse physiological contexts. This review highlights how new global approaches combining classic analysis with new sequencing techniques may usher in an era of bacterial epitranscriptomics. PMID- 26803286 TI - Effectiveness of cognitive behavioural therapy (CBT) programmes for anxiety or depression in adults with intellectual disabilities: A review of the literature. AB - Relatively little is known about the application of cognitive behavioural therapy (CBT) to people with intellectual disabilities (ID). This review sought to synthesise available evidence on the effectiveness of CBT for anxiety or depression to assess the current level of evidence and make recommendations for future research. A comprehensive systematic literature search was conducted to identify qualitative and quantitative studies. Robust criteria were applied to select papers that were relevant to the review. Included papers were subject to quality appraisal. Eleven out of the 223 studies considered met our inclusion criteria and were included in the review in which CBT was used with participants with ID and anxiety (n=3), depression (n=4) or a mixed clinical presentation (n=4). There remains a paucity of evidence of effectiveness, however, the studies indicate that CBT is feasible and well-tolerated and may be effective in reducing symptoms of depression among adults with mild ID. Qualitative data reflect a positive perception of CBT amongst clients and carers. Further research is required to investigate the components of CBT, suitability for CBT, and requisite skills for CBT, which uses valid, sensitive and more holistic outcome measures. PMID- 26803288 TI - Sustained high blood pressure reduction with etamicastat, a peripheral selective dopamine beta-hydroxylase inhibitor. AB - The aim of the present study was to evaluate the influence of chronic inhibition of dopamine beta-hydroxylase by etamicastat on the development of hypertension in the spontaneously hypertensive rat (SHR) and the sustainability of effects on the systolic and diastolic blood pressure in the SHR and the normotensive Wistar Kyoto rat (WKY). WKY and SHR received etamicastat (10 mg/kg/d) from 5 weeks of age for 35 weeks in drinking water, and cardiovascular assessments were performed on a weekly basis. Etamicastat reduced systolic and diastolic blood pressure when SHRs reached the age of 16 weeks with mean decreases of 37 and 32 mm Hg, respectively, for the subsequent for 24 weeks of treatment, but did not prevent the increase in blood pressure (BP) aged between 5 and 11 week. The BP lowering effect of etamicastat in SHR was reversible on discontinuation and quickly resumed after reinstatement of therapy and was not accompanied by changes in heart rate. Etamicastat affected neither BP nor heart rate in WKY during 36 weeks of treatment. Etamicastat reduced urinary excretion of norepinephrine to a similar extent in WKY and SHR, accompanied by significant increases in urinary dopamine in SHR. Chronic administration of etamicastat did not adversely affected development of animals. Chronic dopamine beta-hydroxylase inhibition with etamicastat effectively decreases BP, although does not prevent the development of hypertension in the SHR. PMID- 26803290 TI - A robust aCGH data recovery framework based on half quadratic minimization. AB - This paper presents a general half quadratic framework for simultaneous analysis of the whole array comparative genomic hybridization (aCGH) profiles in a data set. The proposed framework accommodates different M-estimation loss functions and two underlying assumptions for aCGH profiles of a data set: sparsity and low rank. Using M-estimation loss functions, this framework is more robust to various types of noise and outliers. The solution of the proposed framework is given by half quadratic (HQ) minimization. To hasten this procedure, accelerated proximal gradient (APG) is utilized. Experimental results support the robustness of the proposed framework in comparison to the state-of-the-art algorithms. PMID- 26803289 TI - Longitudinal imaging of microvascular remodelling in proliferative diabetic retinopathy using adaptive optics scanning light ophthalmoscopy. AB - PURPOSE: To characterise longitudinal changes in the retinal microvasculature of type 2 diabetes mellitus (T2DM) as exemplified in a patient with proliferative diabetic retinopathy (PDR) using an adaptive optics scanning light ophthalmoscope (AOSLO). METHODS: A 35-year-old T2DM patient with PDR treated with scatter pan retinal photocoagulation at the inferior retina 1 day prior to initial AOSLO imaging along with a 24-year-old healthy control were imaged in this study. AOSLO vascular structural and perfusion maps were acquired at four visits over a 20 week period. Capillary diameter and microaneurysm area changes were measured on the AOSLO structural maps. Imaging repeatability was established using longitudinal imaging of microvasculature in the healthy control. RESULTS: Capillary occlusion and recanalisation, capillary dilatation, resolution of local retinal haemorrhage, capillary hairpin formation, capillary bend formation, microaneurysm formation, progression and regression were documented over time in a region 2 degrees superior to the fovea in the PDR patient. An identical microvascular network with same capillary diameter was observed in the control subject over time. CONCLUSIONS: High-resolution serial AOSLO imaging enables in vivo observation of vasculopathic changes seen in diabetes mellitus. The implications of this methodology are significant, providing the opportunity for studying the dynamics of the pathological process, as well as the possibility of identifying highly sensitive and non-invasive biomarkers of end organ damage and response to treatment. PMID- 26803291 TI - Shape changes of bioprinted tissue constructs simulated by the Lattice Boltzmann method. AB - Tissue engineers seek to build living tissue constructs for replacing or repairing damaged tissues. Computational methods foster tissue engineering by pointing out dominant mechanisms involved in shaping multicellular systems. Here we apply the Lattice Boltzmann (LB) method to study the fusion of multicellular constructs. This process is of interest in bioprinting, in which multicellular spheroids or cylinders are embedded in a supportive hydrogel by a computer controlled device. We simulated post-printing rearrangements of cells, aiming to predict the shape and stability of certain printed structures. To this end, we developed a two-dimensional LB model of a multicellular system in a hydrogel. Our parallel computing code was implemented using the Portable Extensible Toolkit for Scientific Computation (PETSc). To validate the LB model, we simulated the fusion of multicellular cylinders in a contiguous, hexagonal arrangement. Our two dimensional LB simulation describes the evolution of the transversal cross section of the construct built from three-dimensional multicellular cylinders whose length is much larger than their diameter. Fusion eventually gave rise to a tubular construct, in qualitative agreement with bioprinting experiments. Then we simulated the time course of a defect in a bioprinted tube. To address practical problems encountered in tissue engineering, we also simulated the evolution of a planar construct, as well as of a bulky, perfusable construct made of multicellular cylinders. The agreement with experiments indicates that our LB model captures certain essential features of morphogenesis, and, therefore, it may be used to test new working hypotheses faster and cheaper than in the laboratory. PMID- 26803292 TI - Toddlers' Verb Lexicon Diversity and Grammatical Outcomes. AB - PURPOSE: The goals of this study were to quantify longitudinal expectations for verb lexicon growth and to determine whether verb lexicon measures were better predictors of later grammatical outcomes than noun lexicon measures. METHOD: Longitudinal parent-report measures from the MacArthur-Bates Communicative Development Inventory (Fenson et al., 2007) from ages 21 to 30 months from an archival database were used to model growth in common noun and verb lexicon size for 45 typically developing toddlers. Communicative Development Inventory growth coefficients and 24-month measures of lexical diversity from spontaneous language samples were used to predict 30-month grammatical outcomes on the Index of Productive Syntax (Scarborough, 1990). RESULTS: Average verb growth was characterized by 50.57 verbs at 24 months, with linear growth of 8.29 verbs per month and deceleration overall. Children with small verb lexicons or slow linear growth at 24 months accelerated during this developmental period. Verb lexicon measures were better predictors of grammatical outcomes than noun lexicon measures, accounting for 47.8% of the variance in Index of Productive Syntax scores. Lexical verb diversity in spontaneous speech emerged as the single best predictor. CONCLUSION: Measures of verb lexicon size and diversity should be included as part of early language assessment to guide clinical decision making with young children at risk for language impairment. PMID- 26803293 TI - Independent mitochondrial and nuclear exchanges arising in Rhizophagus irregularis crossed-isolates support the presence of a mitochondrial segregation mechanism. AB - BACKGROUND: Arbuscular mycorrhizal fungi (AMF) are members of the phylum Glomeromycota, an early divergent fungal lineage that forms symbiotic associations with the large majority of land plants. These organisms are asexual obligate biotrophs, meaning that they cannot complete their life cycle in the absence of a suitable host. These fungi can exchange genetic information through hyphal fusions (i.e. anastomosis) with genetically compatible isolates belonging to the same species. The occurrence of transient mitochondrial length heteroplasmy through anastomosis between geographically distant Rhizophagus irregularis isolates was previously demonstrated in single spores resulting from crossing experiments. However, (1) the persistence of this phenomenon in monosporal culture lines from crossed parental isolates, (2) its correlation with nuclear exchanges and (3) the potential mechanisms responsible for mitochondrial inheritance are still unknown. Using the AMF model organism R. irregularis, we tested whether the presence of a heteroplasmic state in progeny spores was linked to the occurrence of nuclear exchanges and whether the previously observed heteroplasmic state persisted in monosporal in vitro crossed-culture lines. We also investigated the presence of a putative mitochondrial segregation apparatus in Glomeromycota by identifying proteins similar to those found in other fungal groups. RESULTS: We observed the occurrence of biparental inheritance both for mitochondrial and nuclear markers tested in single spores obtained from crossed isolates. However, only one parental mitochondrial DNA and nuclear genotype were recovered in each monosporal crossed-cultures, with an overrepresentation of certain mitochondrial haplotypes. These results strongly support the presence of a nuclear-independent mitochondrial segregation mechanism in R. irregularis. Furthermore, a nearly complete set of genes was identified with putative orthology to those found in other fungi and known to be associated with the mitochondrial segregation in Saccharomyces cerevisiae and filamentous fungi. CONCLUSIONS: Our findings suggest that mitochondrial segregation might take place either during spore formation or colony development and that it might be independent of the nuclear segregation machinery. We present the basic building blocks for a better understanding of the mitochondrial inheritance process and segregation in these important symbiotic fungi. The comprehension of these processes is of great importance since it has been shown that different segregated lines of the same isolate can have variable effects on the host plant. PMID- 26803294 TI - Validating survey measurement scales for AIDS-related knowledge and stigma among construction workers in South Africa. AB - BACKGROUND: Construction workers in South Africa are regarded as a high-risk group in the context of HIV/AIDS. HIV testing is pivotal to controlling HIV transmission and providing palliative care and AIDS-related knowledge and stigma are key issues in addressing the likelihood of testing behaviour. In exploring these issues, various studies have employed an 11-item AIDS-related knowledge scale (Kalichman and Simbayi, AIDS Care 16:572-580, 2004) and a 9-item stigma scale (Kalichman et al., AIDS Behav 9:135-143, 2005), but little evidence exists confirming the psychometric properties of these scales. METHODS: Using survey data from 512 construction workers in the Western Cape, South Africa, this research examines the validity and reliability of the two scales through exploratory and confirmatory factor analysis and internal consistency tests. RESULTS: From confirmatory factor analysis, a revised 10-item knowledge scale was developed (chi2 /df ratio = 1.675, CFI = 0.982, RMSEA = 0.038, and Hoelter (95 %) = 393). A revised 8-item stigma scale was also developed (chi2 /df ratio = 1.929, CFI = 0.974, RMSEA = 0.045, and Hoelter (95 %) = 380). Both revised scales demonstrated good model fit and all factor loadings were significant (p < 0.01). Reliability analysis demonstrated excellent to good internal consistency, with alpha values of 0.80 and 0.74, respectively. Both revised scales also demonstrated satisfactory convergent and divergent validity. Limitations of the original survey from which the data was obtained include the failure to properly account for respondent selection of language for completion of the survey, use of ethnicity as a proxy for identifying the native language of participants, the limited geographical area from which the survey data was collected, and the limitations associated with the convenience sample. A limitation of the validation study was the lack of available data for a more robust examination of reliability beyond internal consistency, such as test-retest reliability. CONCLUSIONS: The revised knowledge and stigma scales offered here hold considerable promise as measures of AIDS-related knowledge and stigma among South African construction workers. PMID- 26803295 TI - Near normal HbA1c with stable glucose homeostasis: the ultimate target/aim of diabetes therapy. AB - Achieving near normal glucose homeostasis implies that all components of dysglycemia that are present in diabetes states be eliminated. Reducing ambient/overall hyperglycemia is a pre-requisite to eliminate the risk of development and progression of diabetes complications. More controversially however, are the relative and related contributions of postprandial glucose excursions, glucose variability, hypoglycemia and the dawn phenomenon across the spectrum of dysglycemia. For instance, it is likely that the dawn phenomenon contributes to ambient hyperglycemia and that postprandial glucose excursions are at the cross road of ambient hyperglycemia and glucose variability with glucose fluctuations as causative risk factors for hypoglycemia. Proof-of-concept trials such as the ongoing FLAT-SUGAR study are necessary for gaining further insight into the possible harmful effects of some of these features such as excessive glycemic variability and glucose excursions, still considered to be of minor relevance by several diabetologists. Whether their role will be more thoroughly proven through further intervention trials with "hard" endpoints, remains to be seen. In the meantime more consideration should be given to medications aimed at concomitantly reducing ambient/overall hyperglycemia and those additional abnormal glycemic features of dysglycemia. PMID- 26803296 TI - Rib-vertebral angle measurements predict brace treatment outcome in Risser grade 0 and premenarchal girls with adolescent idiopathic scoliosis. AB - PURPOSE: To investigate the predictive role of rib-vertebral angle (RVA) measurements in early adolescent idiopathic scoliosis (AIS) girls with right thoracic curve during brace treatment. METHODS: Early AIS (premenarchal and Risser 0) girls who had undergone brace treatment and had been followed regularly were recruited to this study. According to the bracing outcome, they were divided into Group A (non-progressed) and Group B (curve worsened over six degrees or indicated for surgery). RESULTS: Totally 48 girls were included. There were 30 and 18 patients in Groups A and B, respectively. Ratio of curve progression was significantly higher in patients with initial RVA difference (RVAD) >=20 degrees versus <20 degrees , or convex RVA (CRVA) <=68 degrees versus >68 degrees . From brace initiation to the latest follow-up, CRVA was found to be significantly higher in Group A versus Group B (P < 0.05), while RVAD was higher in Group B versus Group A (P < 0.05). Serial measurements revealed an increasing trend for RVAD (from 19 +/- 10 degrees to 29 +/- 8 degrees ) yet a decreasing trend for CRVA (from 68 +/- 6 degrees to 60 +/- 7 degrees ) in Group B, but both RVAD and CRVA were found to remain stable in Group A during the follow-up period. Association analyses showed that both RVAD >=20 degrees and CRVA <=68 degrees at brace initiation and at each follow-up were significantly associated with curve progression. CONCLUSIONS: The initial RVAD >=20 degrees and CRVA <=68 degrees serve as valid factors in predicting the risk of curve progression during bracing in early AIS. Constant watch on RVAD and CRVA can help to more accurately predict the effectiveness of bracing in these patients. PMID- 26803297 TI - Using regression models to evaluate the formation of trihalomethanes and haloacetonitriles via chlorination of source water with low SUVA values in the Yangtze River Delta region, China. AB - The purpose of this study was to develop the multiple regression models to evaluate the formation of trihalomethanes (THMs) and haloacetonitriles (HANs) during chlorination of source water with low specific ultraviolet absorbance (SUVA) in Yangtze River Delta, China. The results showed that the regression models of THMs exhibited good accuracy and precision, and 86-97 % of the calculated values fell within +/-25 % of the measured values. While the HANs models showed relatively weak evaluation ability, as only 75-83 % of the calculated values were within +/-25 % of the measured values. The organic matter [dissolved organic carbon (DOC) or UV absorbance at 254 nm] and bromide exerted the most important influence on the formation of HANs. While for THMs, besides the organic matter and bromide, reaction time was also a key factor. Comparing the models for total THMs (T-THMs) in this study with others revealed that the regression models from the low SUVA waters may have low DOC coefficients, but high bromide coefficients as compared with those from the high SUVA waters. PMID- 26803298 TI - Free establishment of primary health care providers: effects on geographical equity. AB - BACKGROUND: A reform in 2010 in Swedish primary care made it possible for private primary care providers to establish themselves freely in the country. In the former, publicly planned system, location was strictly regulated by local authorities. The goal of the new reform was to increase access and quality of health care. Critical arguments were raised that the reform could have detrimental effects on equity if the new primary health care providers chose to establish foremost in socioeconomically prosperous areas. The aim of this study is to examine how the primary care choice reform has affected geographical equity by analysing patterns of establishment on the part of new private providers. METHODS: The basis of the design was to analyse socio-economic data on individuals who reside in the same electoral areas in which the 1411 primary health care centres in Sweden are established. Since the primary health care centres are located within 21 different county councils with different reimbursement schemes, we controlled for possible cluster effects utilizing generalized estimating equations modelling. The empirical material used in the analysis is a cross-sectional data set containing socio-economic data of the geographical areas in which all primary health care centres are established. RESULTS: When controlling for the effects of the county council regulation, primary health care centres established after the primary care choice reform were found to be located in areas with significantly fewer older adults living alone as well as fewer single parents - groups which generally have lower socio economic status and high health care needs. However, no significant effects were observed for other socio-economic variables such as mean income, percentage of immigrants, education, unemployment, and children <5 years. CONCLUSIONS: The primary care choice reform seems to have had some negative effects on geographical equity, even though these seem relatively minor. PMID- 26803299 TI - Cotton GhMYB7 is predominantly expressed in developing fibers and regulates secondary cell wall biosynthesis in transgenic Arabidopsis. AB - The secondary cell wall in mature cotton fibers contains over 90% cellulose with low quantities of xylan and lignin. However, little is known regarding the regulation of secondary cell wall biosynthesis in cotton fibers. In this study, we characterized an R2R3-MYB transcription factor, GhMYB7, in cotton. GhMYB7 is expressed at a high level in developing fibers and encodes a MYB protein that is targeted to the cell nucleus and has transcriptional activation activity. Ectopic expression of GhMYB7 in Arabidopsis resulted in small, curled, dark green leaves and also led to shorter inflorescence stems. A cross-sectional assay of basal stems revealed that cell wall thickness of vessels and interfascicular fibers was higher in transgenic lines overexpressing GhMYB7 than in the wild type. Constitutive expression of GhMYB7 in Arabidopsis activated the expression of a suite of secondary cell wall biosynthesis-related genes (including some secondary cell wall-associated transcription factors), leading to the ectopic deposition of cellulose and lignin. The ectopic deposition of secondary cell walls may have been initiated before the cessation of cell expansion. Moreover, GhMYB7 was capable of binding to the promoter regions of AtSND1 and AtCesA4, suggesting that GhMYB7 may function upstream of NAC transcription factors. Collectively, these findings suggest that GhMYB7 is a potential transcriptional activator, which may participate in regulating secondary cell wall biosynthesis of cotton fibers. PMID- 26803300 TI - Two-dimensional gel electrophoresis-based analysis provides global insights into the cotton ovule and fiber proteomes. AB - Proteomic analysis of upland cotton was performed to profile the global detectable proteomes of ovules and fibers using two-dimensional electrophoresis (2DE). A total of 1,203 independent protein spots were collected from representative 2DE gels, which were digested with trypsin and identified by matrix-assisted laser desorption and ionization-time-offlight/ time-of-flight (MALDI-TOF/TOF) mass spectrometry. The mass spectrometry or tandem mass spectrometry (MS or MS/MS) data were then searched against a local database constructed from Gossypium hirsutum genome sequences, resulting in successful identification of 975 protein spots (411 for ovules and 564 for fibers). Functional annotation analysis of the 975 identified proteins revealed that ovule specific proteins were mainly enriched in functions related to fatty acid elongation, sulfur amino acid metabolism and post-replication repair, while fiber specific proteins were enriched in functions related to root hair elongation, galactose metabolism and D-xylose metabolic processes. Further annotation analysis of the most abundant protein spots showed that 28.96% of the total proteins in the ovule were mainly located in the Golgi apparatus, endoplasmic reticulum, mitochondrion and ribosome, whereas in fibers, 27.02% of the total proteins were located in the cytoskeleton, nuclear envelope and cell wall. Quantitative real-time polymerase chain reaction (qRT-PCR) analyses of the ovule specific protein spots P61, P93 and P198 and fiber-specific protein spots 230, 477 and 511 were performed to validate the proteomics data. Protein-protein interaction network analyses revealed very different network cluster patterns between ovules and fibers. This work provides the largest protein identification dataset of 2DE-detectable proteins in cotton ovules and fibers and indicates potentially important roles of tissue-specific proteins, thus providing insights into the cotton ovule and fiber proteomes on a global scale. PMID- 26803301 TI - Phytosterol content and the campesterol:sitosterol ratio influence cotton fiber development: role of phytosterols in cell elongation. AB - Phytosterols play an important role in plant growth and development, including cell division, cell elongation, embryogenesis, cellulose biosynthesis, and cell wall formation. Cotton fiber, which undergoes synchronous cell elongation and a large amount of cellulose synthesis, is an ideal model for the study of plant cell elongation and cell wall biogenesis. The role of phytosterols in fiber growth was investigated by treating the fibers with tridemorph, a sterol biosynthetic inhibitor. The inhibition of phytosterol biosynthesis resulted in an apparent suppression of fiber elongation in vitro or in planta. The determination of phytosterol quantity indicated that sitosterol and campesterol were the major phytosterols in cotton fibers; moreover, higher concentrations of these phytosterols were observed during the period of rapid elongation of fibers. Furthermore, the decrease and increase in campesterol:sitosterol ratio was associated with the increase and decease in speed of elongation, respectively, during the elongation stage. The increase in the ratio was associated with the transition from cell elongation to secondary cell wall synthesis. In addition, a number of phytosterol biosynthetic genes were down-regulated in the short fibers of ligon lintless-1 mutant, compared to its near-isogenic wild-type TM-1. These results demonstrated that phytosterols play a crucial role in cotton fiber development, and particularly in fiber elongation. PMID- 26803302 TI - Transcriptome analysis reveals long noncoding RNAs involved in fiber development in cotton (Gossypium arboreum). AB - Long noncoding RNAs (lncRNAs) play important roles in various biological regulatory processes in yeast, mammals, and plants. However, no systematic identification of lncRNAs has been reported in Gossypium arboreum. In this study, the strand-specific RNA sequencing (ssRNA-seq) of samples from cotton fibers and leaves was performed, and lncRNAs involved in fiber initiation and elongation processes were systematically identified and analyzed. We identified 5,996 lncRNAs, of which 3,510 and 2,486 can be classified as long intergenic noncoding RNAs (lincRNAs) and natural antisense transcripts (lncNAT), respectively. LincRNAs and lncNATs are similar in many aspects, but have some differences in exon number, exon length, and transcript length. Expression analysis revealed that 51.9% of lincRNAs and 54.5% of lncNATs transcripts were preferentially expressed at one stage of fiber development, and were significantly highly expressed than protein-coding transcripts (21.7%). During the fiber and rapid elongation stages, rapid and dynamic changes in lncRNAs may contribute to fiber development in cotton. This work describes a set of lncRNAs that are involved in fiber development. The characterization and expression analysis of lncRNAs will facilitate future studies on their roles in fiber development in cotton. PMID- 26803303 TI - The post-genomics era of cotton. PMID- 26803304 TI - Gossypol: phytoalexin of cotton. AB - Sesquiterpenoids are a class of 15-carbon secondary metabolites that play diverse roles in plant adaptation to environment. Cotton plants accumulate a large amount of sesquiterpene aldehydes (including gossypol) as phytoalexins against pathogens and herbivores. They are stored in pigment glands of aerial organs and in epidermal layers of roots. Several enzymes of gossypol biosynthesis pathway have been characterized, including 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) and farnesyl diphosphate synthase (FPS) that catalyze the formation of the precursor farnesyl diphosphate (FPP), (+)-delta-cadinene synthase (CDN) which is the first enzyme committed to gossypol biosynthesis, and the downstream enzymes of CYP706B1 and methyltransferase. Expressions of these genes are tightly regulated during cotton plants development and induced by jasmonate and fungi elicitors. The transcription factor GaWRKY1 has been shown to be involved in gossypol pathway regulation. Recent development of new genomic platforms and methods and releases of diploid and tetraploid cotton genome sequences will greatly facilitate the elucidation of gossypol biosynthetic pathway and its regulation. PMID- 26803305 TI - The two domains of cotton WLIM1a protein are functionally divergent. AB - Our previous study demonstrated that WLIM1a has dual roles in fiber elongation and secondary cell wall synthesis in upland cotton, and the protein acts either as an actin-binding protein or as a transcription factor. Because WLIM1a consists of two different LIM domains, it is possible that these elements contribute differentially to the dual functions of the protein. In this study, we dissected the two LIM domains and characterized their biochemical functions. By using red fluorescent protein (RFP) fusion, co-sedimentation, and DNA binding methods, we found that the two domains of WLIM1a, domain1 (D1) and domain2 (D2), possessed different biochemical properties. While D1 contributed primarily to the actin filament-bundling activity of WLIM1a, D2 contributed to the DNA-binding activity of the protein; both D1 and D2 relied on a linker sequence for their activities. In addition, we found that WLIM1a and its two LIM domains form dimers in vitro. These results may lead to a better understanding of the molecular mechanisms of dual functions of WLIM1a during cotton fiber development. PMID- 26803308 TI - 1st World Conference on Abdominal Wall Hernia Surgery, Milan, April 2015. PMID- 26803306 TI - Comprehensive analysis of NAC transcription factors in diploid Gossypium: sequence conservation and expression analysis uncover their roles during fiber development. AB - Determining how function evolves following gene duplication is necessary for understanding gene expansion. Transcription factors (TFs) are a class of proteins that regulate gene expression by binding to specific cis-acting elements in the promoters of target genes, subsequently activating or repressing their transcription. In the present study, we systematically examined the functional diversification of the NAC transcription factor (NAC-TFs) family by analyzing their chromosomal location, structure, phylogeny, and expression pattern in Gossypium raimondii (Gr) and G. arboreum (Ga). The 145 and 141 NAC genes identified in the Gr and Ga genomes, respectively, were annotated and divided into 18 subfamilies, which showed distinct divergence in gene structure and expression patterns during fiber development. In addition, when the functional parameters were examined, clear divergence was observed within tandem clusters, which suggested that subfunctionalization had occurred among duplicate genes. The expression patterns of homologous gene pairs also changed, suggestive of the diversification of gene function during the evolution of diploid cotton. These findings provide insights into the mechanisms underlying the functional differentiation of duplicated NAC-TFs genes in two diploid cotton species. PMID- 26803309 TI - CB1 Cannabinoid Agonist (WIN55,212-2) Within the Basolateral Amygdala Induced Sensitization to Morphine and Increased the Level of MU-Opioid Receptor and c-fos in the Nucleus Accumbens. AB - The basolateral amygdala (BLA) is rich of CB1 cannabinoid receptors (CB1R) and has reciprocal connections with the nucleus accumbens (NAc) which is involved in opioid sensitization. In this study, effects of intra-BLA administration of CB1R agonist on sensitization to antinociceptive effect of morphine and changes in the levels of MU-opioid receptor (MOR), p-CREB, and c-fos in the NAc were investigated. Animals received intra-BLA microinjection of CB1R agonist (WIN55,212-2) once daily for 3 days consecutively (sensitization period). After 5 days free of drug, tail-flick test was performed before and after the administration of an ineffective dose of morphine. Afterward, the levels of MOR, p-CREB, and c-fos proteins were measured in the NAc by Western blot analysis. The results indicated that intra-BLA injection of WIN55,212-2 during sensitization period resulted in the induction of antinociceptive responses by ineffective dose of morphine and caused a significant increase in the MOR and c-fos levels but not p-CREB/CREB ratio in the NAc. These finding revealed that CB1 receptor agonist in the BLA induces development of morphine sensitization and increases expression of MOR in the NAc. It seems that c-fos is one of the important factors involved in the induction of sensitization to antinociceptive effect of morphine. PMID- 26803310 TI - Novel Approaches in Astrocyte Protection: from Experimental Methods to Computational Approaches. AB - Astrocytes are important for normal brain functioning. Astrocytes are metabolic regulators of the brain that exert many functions such as the preservation of blood-brain barrier (BBB) function, clearance of toxic substances, and generation of antioxidant molecules and growth factors. These functions are fundamental to sustain the function and survival of neurons and other brain cells. For these reasons, the protection of astrocytes has become relevant for the prevention of neuronal death during brain pathologies such as Parkinson's disease, Alzheimer's disease, stroke, and other neurodegenerative conditions. Currently, different strategies are being used to protect the main astrocytic functions during neurological diseases, including the use of growth factors, steroid derivatives, mesenchymal stem cell paracrine factors, nicotine derivatives, and computational biology tools. Moreover, the combined use of experimental approaches with bioinformatics tools such as the ones obtained through system biology has allowed a broader knowledge in astrocytic protection both in normal and pathological conditions. In the present review, we highlight some of these recent paradigms in assessing astrocyte protection using experimental and computational approaches and discuss how they could be used for the study of restorative therapies for the brain in pathological conditions. PMID- 26803312 TI - Perceived Spirituality, Mindfulness and Quality of Life in Psychiatric Patients. AB - There is some evidence of the relationship between spirituality and quality of life, but there are few bibliographic references on these constructs for patients suffering from mental illness; thus, this study was aimed at revealing the possible role of spiritual outlooks as a protective factor in these individuals. The sample consisted of 96 Portuguese psychiatric patients, selected from a psychiatric hospital and assessed based on parameters for quality of life, spirituality and mindfulness. The data support some theories about the nature of the spirituality. Spiritual beliefs are poorly correlated with the quality of life index, and there is a moderate association between these beliefs and some aspects of mindfulness. It is suggested that a spiritual outlook of psychiatric patients should be taken into account in psychological interventions. PMID- 26803311 TI - Serum Response Factor Protects Retinal Ganglion Cells Against High-Glucose Damage. AB - Serum response factor (SRF), which encodes the MADS-box family of related proteins, is a common transcription factor related to the expression of genes associated with cell survival. However, SRF's role in retinal ganglion cells (RGCs) after high-glucose injury remains unclear. In this study, we investigate the protective role of SRF after high-glucose injury and its underlying mechanism. The in vitro RGC model subjected to high glucose was established by employing a 50 mmol/L glucose culture environment. As detected by real-time quantitative PCR and Western blot, SRF was significantly upregulated in RGCs treated with high glucose. Overexpression of SRF significantly promoted survival among RGCs exposed to high glucose and inhibited RGC apoptosis. Knockdown of SRF exerted an inverse effect. Moreover, SRF upregulation enhanced expression of an antioxidant protein, nuclear factor erythroid 2-related factor (Nrf2), via control of the Fos-related antigen 1 (Fra-1). SRF upregulation also affected RGC survival after high-glucose treatment. Our findings showed that overexpression of SRF promoted survival of RGCs after high-glucose injury by regulating Fra-1 and Nrf2. PMID- 26803313 TI - Metabolomics study of fatigue in patients with rheumatoid arthritis naive to biological treatment. AB - Fatigue occurs in all chronic inflammatory diseases, in cancer, and in some neurological conditions. Patients often regard fatigue as one of their most debilitating problems, but currently there is no established treatment and the mechanisms that lead to and regulate fatigue are incompletely understood. Our objective was to more completely understand the physiology of this phenomenon. Twenty-four patients with rheumatoid arthritis (RA) naive to treatment with biological drugs were enrolled for the study. Fatigue was measured with a fatigue visual analogue scale (fVAS). Ethylenediaminetetraacetic acid (EDTA) plasma samples were subjected to gas chromatography-time-of-flight mass spectrometry (GC/MS-TOF)-based metabolite profiling. Obtained metabolite data were evaluated by multivariate data analysis with orthogonal projections to latent structures (OPLS) method to pinpoint metabolic changes related to fatigue severity. A significant multivariate OPLS model was obtained between the fVAS scores and the measured metabolic levels. Increasing fatigue scores were associated with a metabolic pattern characterized by down-regulation of metabolites from the urea cycle, fatty acids, tocopherols, aromatic amino acids, and hypoxanthine. Uric acid levels were increased. Apart from fatigue, we found no other disease-related variables that might be responsible for these changes. Our MS-based metabolomic approach demonstrated strong associations between fatigue and several biochemical patterns related to oxidative stress. PMID- 26803315 TI - Prevalence of burnout among Irish general practitioners: a cross-sectional study. AB - BACKGROUND: Burnout constitutes a significant problem among physicians which impacts negatively upon both the doctor and their patients. Previous research has indicated that burnout is prevalent among primary care physicians in other European countries and North America. However, there is a paucity of research assessing burnout among Irish general practitioners and examining predictive factors. AIMS: To report the findings of a survey of burnout among Irish general practitioners, and assess variables related to burnout in this population. METHODS: An online, anonymous questionnaire was distributed to general practitioners working in the Republic of Ireland. RESULTS: In total, 683 general practitioners (27.3 % of practising Irish general practitioners) completed the survey. Of these, 52.7 % reported high levels of emotional exhaustion, 31.6 % scored high on depersonalisation and 16.3 % presented with low levels of personal accomplishment. In total, 6.6 % presented with all three symptoms, fulfilling the criteria for burnout. Emotional exhaustion was higher among this sample than that reported in European and UK studies of burnout in general practitioners. Personal accomplishment was, however, higher in this sample than in other studies. Multiple regression analyses revealed that younger age, non-principal status role, and male gender were related to increased risk of burnout symptoms. CONCLUSIONS: The symptoms of burnout appear prevalent among Irish general practitioners. This is likely to have a detrimental impact both upon the individual general practitioners and the patients that they serve. Research investigating the factors contributing to burnout in this population, and evaluating interventions to improve general practitioner well-being, is, therefore, essential. PMID- 26803314 TI - TRPM8: a potential target for cancer treatment. AB - Transient receptor potential (TRP) cation channel superfamily plays critical roles in variety of processes, including temperature perception, pain transduction, vasorelaxation, male fertility, and tumorigenesis. One of seven families within the TRP superfamily of ion channels, the melastatin, or TRPM family comprises a group of eight structurally and functionally diverse channels. Of all the members of TRPM subfamily, TRPM8 is the most notable one. A lot of literatures have demonstrated that transient receptor potential melastatin 8 (TRPM8) could perform a myriad of functions in vertebrates and invertebrates alike. In addition to its well-known function in cold sensation, TRPM8 has an emerging role in a variety of biological systems, including thermoregulation, cancer, bladder function, and asthma. Recent studies have shown that TRPM8 is necessary to the initiation and progression of tumors, and the aberrant expression of TRPM8 was found in varieties of tumors, such as prostate tumor, melanoma, breast adenocarcinoma, bladder cancer, and colorectal cancer, making it a novel molecular target potentially useful in the diagnosis and treatment of cancer. This review outlines our current understanding on the role of TRPM8 in occurrence and development of different kinds of tumor and also includes discussion about the regulation of TRPM8 during carcinogenesis as well as therapeutic potential of targeting TRPM8 in tumor, which may be utilized for a potential pharmacological use as a target for anti-cancer therapy. PMID- 26803316 TI - Effect of rectal enemas on rectal dosimetric parameters during high-dose-rate vaginal cuff brachytherapy: A prospective trial. AB - PURPOSE: To evaluate the effects of rectal enemas on rectal doses during postoperative high-dose-rate (HDR) vaginal cuff brachytherapy (VCB). PATIENTS AND METHODS: This prospective trial included 59 patients. Two rectal cleansing enemas were self-administered before the second fraction, and fraction 1 was considered the basal status. Dose-volume histogram (DVH) values were generated for the rectum and correlated with rectal volume variation. Statistical analyses used paired and unpaired t-tests. RESULTS: Despite a significant 15 % reduction in mean rectal volume (44.07 vs. 52.15 cc, p = 0.0018), 35.6 % of patients had larger rectums after rectal enemas. No significant rectal enema-related DVH differences were observed compared to the basal data. Although not statistically significant, rectal cleansing-associated increases in mean rectal DVH values were observed: D0.1 cc: 6.6 vs. 7.21 Gy; D1 cc: 5.35 vs. 5.52 Gy; D2 cc: 4.67 vs. 4.72 Gy, before and after rectal cleaning, respectively (where Dx cc is the dose to the most exposed x cm(3)). No differences were observed in DVH parameters according to rectal volume increase or decrease after the enema. Patients whose rectal volume increased also had significantly larger DVH parameters, except for D5 %, D25 %, and D50 %. In contrast, in patients whose rectal volume decreased, significance was only seen for D25 % and D50 % (Dx % dose covering x % of the volume). In the latter patients, nonsignificant reductions in D2 cc, D5 cc and V5 Gy (volume receiving at least 5 Gy) were observed. CONCLUSION: The current rectal enemas protocol was ineffective in significantly modifying rectal DVH parameters for HDR-VCB. PMID- 26803317 TI - Passive rGE or Developmental Gene-Environment Cascade? An Investigation of the Role of Xenobiotic Metabolism Genes in the Association Between Smoke Exposure During Pregnancy and Child Birth Weight. AB - There is considerable evidence that smoke exposure during pregnancy (SDP) environmentally influences birth weight after controlling for genetic influences and maternal characteristics. However, maternal smoking during pregnancy-the behavior that leads to smoke exposure during pregnancy-is also genetically influenced, indicating the potential role of passive gene-environment correlation. An alternative to passive gene-SDP correlation is a cascading effect whereby maternal and child genetic influences are causally linked to prenatal exposures, which then have an 'environmental' effect on the development of the child's biology and behavior. We describe and demonstrate a conceptual framework for disentangling passive rGE from this cascading GE effect using a systems-based polygenic scoring approach comprised of genes shown to be important in the xenobiotic (substances foreign to the body) metabolism pathway. Data were drawn from 5044 families from the Avon Longitudinal Study of Parents and Children with information on maternal SDP, birth weight, and genetic polymorphisms in the xenobiotic pathway. Within a k-fold cross-validation approach (k = 5), we created weighted maternal and child polygenic scores using 18 polymorphisms from 10 genes that have been implicated in the xenobiotic metabolism pathway. Mothers and children shared variation in xenobiotic metabolism genes. Amongst mothers who smoked during pregnancy, neither maternal nor child xenobiotic metabolism polygenic scores were associated with a higher likelihood of smoke exposure during pregnancy, or the severity of smoke exposure during pregnancy (and therefore, neither proposed mechanism was supported), or with child birth weight. SDP was consistently associated with lower child birth weight controlling for the polygenic scores, maternal educational attainment, social class, psychiatric problems, and age. Limitations of the study design and the potential of the framework using other designs are discussed. PMID- 26803318 TI - Management of Cardio-Renal Syndrome and Diuretic Resistance. AB - OPINION STATEMENT: Diuretic resistance in acute heart failure has emerged as a powerful predictor of adverse outcome, which is often independent of underlying glomerular filtration rate (GFR). Metrics of diuretic efficacy differ in their accuracy, convenience, and biological plausibility, which should be taken into account when interpreting their results. Loop diuretic efficacy depends on adequate delivery of both the pharmacological agent itself and its substrate (i.e., sodium chloride) to the loop diuretic site of action at the luminal side of the thick ascending limb of Henle's loop. This requires an adequate dosing strategy, with higher doses needed when GFR is low. Importantly, the kidneys are able only to regulate the effective circulatory volume. Thus, specific problems of intravascular volume depletion and poor cardiac output with impaired renal perfusion should be addressed. Addition of thiazide-type diuretics should be considered when a progressive decrease in loop diuretic efficacy is observed with prolonged use (i.e., the braking phenomenon). Furthermore, thiazide-type diuretics are a useful addition in patients with low GFR to maximally boost fractional sodium excretion when nephron perfusion is poor. However, thiazide type diuretics limit free water excretion and should be withheld in cases of hypotonic hyponatremia. Mineralocorticoid receptor antagonists (MRA) and acetazolamide are interesting options to increase loop diuretic efficacy, but further study is needed to assess whether improved diuretic efficacy also translates into clinical outcome benefits. Finally, ultrafiltration should be considered in patients with refractory diuretic resistance as persistent volume overload after decongestive treatment is associated with worse outcomes. Whether more upfront use of individually tailored ultrafiltration is superior to pharmacological therapy remains to be shown by adequately powered randomized clinical trials. PMID- 26803320 TI - Integrated health care: it's time for it to blossom. AB - Considering the grim scenario of burgeoning health-care costs and cost-cutting measures by the Australian Government, there is a clear case to invest and research into disciplines that will ensure sustainability of the public health system. There is evidence that integrated health care contributes to a cost efficient and quality health system because of potential benefits like streamlined care for patients, efficient use of resources, a better cover of patients and improved patient safety. However, integrated health care as a notion is submerged in the disciplines of public health and primary care. In reality, it is a distinct concept acting as a bridge between primary and secondary care. This article argues it is time for the discipline of integrated health care to be recognised on its own and investment be driven into the establishment of integrated care centres. PMID- 26803319 TI - Phenotypic flexibility of energetics in acclimated Siberian hamsters has a narrower scope in winter than in summer. AB - As photoperiod shortens with the approach of winter, small mammals should reduce their energy expenditure to survive periods of food limitation. However, within seasons, animals should balance their energy budgets as abiotic conditions change, sometimes unpredictably; cold spells should increase heat production, while warm spells should do the opposite. Therefore, we addressed specific questions about the possible interactions between seasonal acclimatization and the intra-seasonal phenotypic flexibility of metabolic rate. We hypothesized that phenotypic flexibility in small mammals differs seasonally and is greater in summer than in winter, and predicted that seasonal adjustments in energetics, which are driven by photoperiod, overwhelm the influence of variations in the thermal environment. We measured body mass, basal metabolic rate (BMR), facultative non-shivering thermogenesis (fNST), body temperature, and calculated minimum thermal conductance in Siberian hamsters Phodopus sungorus. Animals were acclimated to winter-like, and then to summer-like conditions and, within each season, were exposed twice, for 3 weeks to 10, 20 or 28 degrees C. We used differences between values measured after these short acclimation periods as a measure of the scope of phenotypic flexibility. After winter acclimation, hamsters were lighter, had lower whole animal BMR, higher fNST than in summer, and developed heterothermy. After these short acclimations to the above-mentioned temperatures, hamsters showed reversible changes in BMR and fNST; however, these traits were less flexible in winter than in summer. We conclude that seasonal acclimation affects hamster responses to intra-seasonal variations in the thermal environment. We argue that understanding seasonal changes in phenotypic flexibility is crucial for predicting the biological consequences of global climate changes. PMID- 26803321 TI - Pre-operative radiological measurement of femoral rotation for prosthetic positioning in total knee arthroplasty. AB - PURPOSE: This study outlines the benefits of the seated view radiograph of the knee in evaluation of the pre-operative individual distal femoral torsion (DFT) and for the follow-up of the post-operative rotational positioning of the femoral component in total knee arthroplasty. METHODS: Study on 20 patients who underwent total knee arthroplasty and the correlation between the DFT measured before surgery with this radiology view, the intra-operative external rotation (ER) necessary for the parallel positioning of the femoral component with the transepicondylar axis (TEA) and the post-operative femoral rotational alignment of the prosthesis on the same view. RESULTS: In 90 % of cases the values of internal DFT were between -1(0) and -8(0), while the mean value of the internal rotation (IR) was -4.45(0). The mean value of the ER applied to the posterior bone resection was 4.25(0) (0(0)-7(0)), showing a statistically significant correlation between the pre-operative measurement and the intra-operative one of the posterior condylar angle (PCA) (r = 0.890, p = 0.000). Residual internal femoral malrotation has been identified in four cases, its mean value being 0.4(0). In three patients the pre-operative value of the PCA was higher than the intra-operative one and an internal malrotation of the post-operative femoral component was observed. CONCLUSIONS: The results are encouraging for the further use of this pre-operative view with the premises of increasing the accuracy of prosthetic positioning and reducing the mechanical complications. PMID- 26803322 TI - Successful osteoconduction but limited cartilage tissue quality following osteochondral repair by a cell-free multilayered nano-composite scaffold at the knee. AB - INTRODUCTION: The treatment of larger osteochondral lesions in the knee is still a clinical challenge. One promising strategy to overcome this problem could be surgical repair by using a cell-free multilayered nano-composite scaffold. METHOD: In this prospective cohort study eight consecutive patients which suffered from a single osteochondral lesion (>=1.5 cm(2)) on the femoral condyle were enrolled. The repair potential of the implant was assessed by using MRI based biochemical MR sequences (T2 mapping) as well as semi-quantitative morphological analyses (MOCART score) at 18 months after the surgery. The clinical outcome was determined at six, 12, 18, and 24 month follow ups by using IKDC, Tegner-Lysholm, and Cincinnati knee scores. RESULTS: Seven out of eight patients showed a complete integration of the scaffold into the border zone and five out of eight patients excellent or good subchondral ossification of the implant at 18 months following implantation. The surface of the repair tissue was found to be intact in all eight patients. T2 mapping data and the zonal T2 index significantly differed in the repair tissue compared to the healthy control cartilage (P < 0.001) which indicates a limited quality of the repair cartilage. The clinical outcome scores consistently improved during the follow up period without reaching statistical significance. CONCLUSIONS: Osteochondral repair by implanting the MaioRegen(r) scaffold provides a successful osteoconduction and filling of the cartilage defect. However there is evidence for a limited repair cartilage tissue quality at 18 months after the surgery. PMID- 26803323 TI - Extranodal Rosai-Dorfman Disease: Clinicopathologic Series of 10 Patients With Radiologic Correlation and Review of the Literature. AB - OBJECTIVES: To describe the radiologic and clinicopathologic features of extranodal Rosai-Dorfman disease (RDD) in our patient population. METHODS: Via a data mining engine, we evaluated 13 cases of extranodal RDD in 10 patients treated at our institution from 2000 to 2014. RESULTS: There was a marked female predominance (90%) in our series. The most common clinical presentation was a palpable, painless mass, which often simulated a neoplasm. Only two cases occurred in children. Multicentric and recurrent disease were uncommon. Histologically, all cases showed large histiocytes with emperipolesis in a mixed inflammatory background, with areas of dense, storiform collagen fibrosis. Positive S-100 and CD68 with negative CD1a in histiocytes are characteristic. CONCLUSIONS: Extranodal RDD is rare and its manifestations varied. It may constitute a clinical and pathologic diagnostic challenge. Clinical suspicion and recognition of its histologic features are necessary for correct diagnosis and avoiding unnecessary treatment. Resection is curative in most cases. PMID- 26803324 TI - Rapid prototyping in aortic surgery. AB - 3D printing provides the sequential addition of material layers and, thus, the opportunity to print parts and components made of different materials with variable mechanical and physical properties. It helps us create 3D anatomical models for the better planning of surgical procedures when needed, since it can reveal any complex anatomical feature. Images of abdominal aortic aneurysms received by computed tomographic angiography were converted into 3D images using a Google SketchUp free software and saved in stereolithography format. Using a 3D printer (Makerbot), a model made of polylactic acid material (thermoplastic filament) was printed. A 3D model of an abdominal aorta aneurysm was created in 138 min, while the model was a precise copy of the aorta visualized in the computed tomographic images. The total cost (including the initial cost of the printer) reached 1303.00 euros. 3D imaging and modelling using different materials can be very useful in cases when anatomical difficulties are recognized through the computed tomographic images and a tactile approach is demanded preoperatively. In this way, major complications during abdominal aorta aneurysm management can be predicted and prevented. Furthermore, the model can be used as a mould; the development of new, more biocompatible, less antigenic and individualized can become a challenge in the future. PMID- 26803325 TI - Are normal-sized ascending aortas at risk of late aortic events after aortic valve replacement for bicuspid aortic valve disease? AB - OBJECTIVES: Bicuspid aortic valve (BAV)-associated aortopathy has been proposed to progress after isolated aortic valve replacement (AVR) surgery, which has been traditionally used as an argument against a TAVR procedure in this clinical subset. Still, more than half of BAV patients have a normal-sized proximal aorta at the time of AVR surgery. We aimed to analyse the long-term risk of adverse aortic events after isolated conventional AVR surgery for BAV and normal-sized proximal aorta. METHODS: A total of 200 consecutive patients (mean age 56 +/- 13 years, 73% men) with BAV disease and ascending aortic diameter of <40 mm underwent isolated conventional AVR from 1995 through 2008 and were identified from our institutional BAV database. Long-term follow-up data (a total of 1532 patient-years) were obtained for all hospital survivors. Composite adverse aortic/cardiovascular events were defined as the need for redo aortic surgery, the occurrence of aortic dissection/rupture, or sudden cardiac death during follow-up. RESULTS: A total of 25 (13%) patients died after a mean follow-up of 8.5 +/- 5 years post-AVR surgery, which resulted in an overall survival rate of 75 +/- 6 and 87 +/- 7% at 15 years postoperatively, for BAV-aortic stenosis and BAV-aortic regurgitation, respectively (P = 0.6). An adverse aortic event occurred in 1 (0.5%) study patient, while 5 (2.5%) further patients suffered sudden cardiac death. Only 1 patient required redo aortic surgery. No documented aortic dissection/rupture occurred. Redo AVR surgery due to endocarditis or structural valve degeneration was performed in 6 (3%) patients. The rate of freedom from composite adverse events was 92 +/- 5 and 95 +/- 4% at 15 years, for the AS and AR subgroups, respectively (P = 0.7). CONCLUSIONS: BAV patients with aortic valve dysfunction and normal-sized ascending aorta are at considerably low risk of late adverse aortic events after isolated AVR. PMID- 26803326 TI - Epicardial ablation of ventricular tachycardia using pericardioscopy through submammary minimal thoracotomy. AB - The subxiphoid access became the standard technique for epicardial ablation of ventricular tachycardia. However, it may prove difficult in certain situations. Here, we report an alternative method of epicardial and endocardial ablation performed via submammary minimal thoracotomy guided by pericardioscopy. Two male patients with structural heart disease and incessant ventricular tachycardia were successfully ablated using this technique. The described technique can be considered as an alternative to the standard technique. Moreover, it permits real time visualization of cardiac vessels and fat tissue, and is safe in terms of damage to the phrenic nerve or potential bleeding complications. PMID- 26803327 TI - Outpatient Parenteral Antimicrobial Therapy in Pediatric Medicaid Enrollees. AB - Background: Outpatient parenteral antimicrobial therapy (OPAT) is overused in cases where highly bioavailable oral alternatives would be equally effective. However, the scope of OPAT use for children nationwide is poorly understood. Our objective was to characterize OPAT use and clinical outcomes for a large population of pediatric Medicaid enrollees treated with OPAT. Methods: We analyzed the Truven MarketScan Medicaid claims database between 2009 and 2012. An OPAT episode was identified by capturing children with claims data indicating home infusion therapy for an intravenous antimicrobial. We characterized OPAT use by describing patient demographics, diagnoses, and antimicrobials prescribed. We categorized an antimicrobial as highly bioavailable if >=80% systemic exposure was expected from the peroral dose. We also determined the percentage of OPAT recipients in whom a follow-up healthcare encounter occurred during the OPAT episode in either the emergency department or as a hospital admission. We reviewed the primary diagnoses associated with these healthcare encounters to determine whether it was related to OPAT. Results: We identified 3433 OPAT episodes in 2687 patients. A total of 4774 antimicrobials were prescribed during these episodes. Ceftriaxone and vancomycin were the most commonly prescribed antimicrobials. Highly bioavailable antimicrobials accounted for 34% of antimicrobials used for OPAT. An emergency department visit or hospital admission occurred during 38% of OPAT episodes, among which 61% were OPAT-related. Conclusions: The high rate of medical encounters associated with OPAT in this cohort and the common prescribing of highly bioavailable antimicrobials underscore the opportunities for antimicrobial stewardship of pediatric OPAT. PMID- 26803329 TI - Nevirapine Plasma Concentrations in Human Immunodeficiency Virus-Exposed Neonates Receiving High-Dose Nevirapine Prophylaxis as Part of 3-Drug Regimen. PMID- 26803328 TI - Immunogenicity, Safety, and Tolerability of Bivalent rLP2086 Meningococcal Group B Vaccine Administered Concomitantly With Diphtheria, Tetanus, and Acellular Pertussis and Inactivated Poliomyelitis Vaccines to Healthy Adolescents. AB - KEY POINTS: Concomitant administration of bivalent rLP2086 (Trumenba [Pfizer, Inc] and diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine (DTaP/IPV) was immunologically noninferior to DTaP/IPV and saline and was safe and well tolerated. Bivalent rLP2086 elicited robust and broad bactericidal antibody responses to diverse Neisseria meningitidis serogroup B strains expressing antigens heterologous to vaccine antigens after 2 and 3 vaccinations. BACKGROUND: Bivalent rLP2086, a Neisseria meningitidis serogroup B (MnB) vaccine (Trumenba [Pfizer, Inc]) recently approved in the United States to prevent invasive MnB disease in individuals aged 10-25 years, contains recombinant subfamily A and B factor H binding proteins (fHBPs). This study evaluated the coadministration of Repevax (diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine [DTaP/IPV]) (Sanofi Pasteur MSD, Ltd) and bivalent rLP2086. METHODS: Healthy adolescents aged >=11 to <19 years received bivalent rLP2086 + DTaP/IPV or saline + DTaP/IPV at month 0 and bivalent rLP2086 or saline at months 2 and 6. The primary end point was the proportion of participants in whom prespecified levels of antibodies to DTaP/IPV were achieved 1 month after DTaP/IPV administration. Immune responses to bivalent rLP2086 were measured with serum bactericidal assays using human complement (hSBAs) against 4 MnB test strains expressing fHBP subfamily A or B proteins different from the vaccine antigens. RESULTS: Participants were randomly assigned to receive bivalent rLP2086 + DTaP/IPV (n = 373) or saline + DTaP/IPV (n = 376). Immune responses to DTaP/IPV in participants who received bivalent rLP2086 + DTaP/IPV were noninferior to those in participants who received saline + DTaP/IPV.The proportions of bivalent rLP2086 + DTaP/IPV recipients with prespecified seroprotective hSBA titers to the 4 MnB test strains were 55.5%-97.3% after vaccination 2 and 81.5%-100% after vaccination 3. The administration of bivalent rLP2086 was well tolerated and resulted in few serious adverse events. CONCLUSIONS: Immune responses to DTaP/IPV administered with bivalent rLP2086 to adolescents were noninferior to DTaP/IPV administered alone. Bivalent rLP2086 was well tolerated and elicited substantial and broad bactericidal responses to diverse MnB strains in a high proportion of recipients after 2 vaccinations, and these responses were further enhanced after 3 vaccinations.ClinicalTrials.gov identifier NCT01323270. PMID- 26803330 TI - Influenza B Burden in Latin America and Potential Benefits of the New Quadrivalent Vaccines. PMID- 26803331 TI - Breakthrough Pain Associated With a Reduction in Serum Buprenorphine Concentration During Dialysis. PMID- 26803332 TI - Author response re. "Rehabilitation nutrition for undernourished participants in nursing home and home care: Cluster randomized controlled study". PMID- 26803333 TI - Nutritional Status and Nutrient Intake Challenges in Children With Spinal Muscular Atrophy. AB - BACKGROUND: Nutrition is recognized as a core component of multidisciplinary care for patients with spinal muscular atrophy, but specific nutritional challenges in this population are not well described. We aimed to describe the nutritional status and nutrient intake in children with spinal muscular atrophy. METHODS: We performed a retrospective medical record review of prospectively collected data from children with spinal muscular atrophy followed at a multidisciplinary clinic at a tertiary referral center. We collected data including clinical parameters; anthropometrics, including weight, height, and body mass index (BMI); and 24-hour dietary intake records in all children followed in the clinic. Available data were found in records from the dietitian as part of a standard evaluation process, and additional clinical data were acquired from patient medical records. Subjects were classified based on spinal muscular atrophy type, and nutritional intake data were compared with dietary reference intakes for gender and age. Z scores were calculated for weight for age (WAZ), height for age, and BMI (BMIZ) using the World Health Organization AnthroPlus software with appropriate World Health Organization reference growth standards. Subjects were classified as malnourished if their WAZ was <-2 or >+2. Anthropometric measurements were obtained at first visit and at a follow-up visit at an average of a 3-year interval between the clinic visits. A decline of more than 0.5 WAZ over this period was defined a priori as significant nutritional deterioration. RESULTS: We analyzed data from 60 subjects, 26 (43%) female, with median age 5.5 years (interquartile range 2 years to 12 years). The cohort consisted of children with spinal muscular atrophy type 1 (28 %), type 2 (45 %), and type 3 (27 %). At the first clinic visit, nine (15%) patients were malnourished. Thirteen (23%) subjects had a significant decline in WAZ from -0.35 (-1.31 to 0.58) to -1.04 ( 2.15 to 0.02) at follow-up after approximately 3 years. A third of these subjects were already malnourished at first visit. A significant decline in BMIZ was noted in 47% of the cohort, and the prevalence of severe malnutrition (BMIZ < -3) increased from 2% to 17% after 3 years. In children receiving specialized enteral nutrition via a feeding tube, overfeeding was recorded in 29% and underfeeding was recorded in 35%. Suboptimal vitamin D intake was recorded in 35% of patients with enteral feeding device. CONCLUSIONS: Malnutrition was prevalent in children with spinal muscular atrophy, and nearly half the cohort demonstrated nutritional deterioration over time. Energy, protein, and vitamin D intakes were inadequate in a majority of the cohort. Underfeeding was highly prevalent, but overfeeding was also present in a third of the enterally fed cohort. Future studies describing optimal nutrient requirements and body composition variables in this group are required. PMID- 26803334 TI - The Way Forward: Challenges and Opportunities in Pediatric Stroke. PMID- 26803335 TI - Supraventricular Tachycardia During Status Epilepticus in Dravet Syndrome: A Link Between Brain and Heart? AB - BACKGROUND: The possibility that epileptic seizures and arrhythmias are different clinical manifestations of a common channelopathy is an interesting but unproved hypothesis. Patients with Dravet syndrome show heart rate variability and affected individuals with arrhythmias have also been documented. The possibility that a genetic mutation affecting sodium channel functions may predispose to both Dravet syndrome and arrhythmogenic disorders is an interesting hypothesis. PATIENT PRESENTATION: We describe a 5-month-old girl with Dravet syndrome who presented with paroxysmal supraventricular tachycardia during status epilepticus. She presented to the hospital the first time with afebrile tonic-clonic seizures and then several subsequent times with status epilepticus confirmed with electroencephalography. During two of these episodes she also exhibited paroxysmal supraventricular tachycardia. She received propofol for status epilepticus and adenosine for the arrhythmia. A clinical and genetic (denovo mutation of a sodium channel, SCN1A) diagnosis of Dravet syndrome was made. CONCLUSIONS: Our patient supports the hypothesis that SCN1A mutation might have a role as a common substrate to both epilepsy and cardiac arrhythmia. More studies are needed to better assess genetic, cardiac, respiratory, and autonomic dysfunction in patients with Dravet syndrome. PMID- 26803336 TI - Lower limb dynamics vary in shod runners who acutely transition to barefoot running. AB - Relative to traditional shod rear-foot strike (RFS) running, habituated barefoot running is associated with a forefoot-strike (FFS) and lower loading rates. Accordingly, barefoot running has been purported to reduce lower-extremity injury risk. Investigations, however, indicate that novice barefoot runners may not innately adopt a FFS. Therefore, the purpose of this study was to examine lower extremity dynamics of habitually shod runners who acutely transition to barefoot running. 22 recreational RFS runners were included in this investigation. This laboratory controlled study consisted of two visits one-week apart, examining habitually shod, then novice barefoot running. Foot-strike patterns and loading rates were determined using motion analysis and force plates, and joint energy absorption was calculated using inverse dynamics. Of the 22 runners, 8 maintained a RFS, 9 adopted a MFS, and 5 adopted a FFS during novice barefoot running. All runners demonstrated a reduction in knee energy absorption when running barefoot; MFS and FFS runners also demonstrated a significant increase in ankle energy absorption. Runners who maintained a RFS presented with loading rates significantly higher than traditional shoe running, whereas FFS runners demonstrated a significant reduction in loading rate. Mid-foot strikers did not demonstrate a significant change in loading rate. These results indicate that habitually shod RFS runners demonstrate a variety of foot-strike and lower extremity dynamic responses during the acute transition to barefoot running. Accordingly, explicit instruction regarding foot-strike patterns may be necessary if transitioning to barefoot. Long-term prospective studies are required in order to determine the influence of FFS barefoot running on injury rates. PMID- 26803337 TI - Enhancing cell-free layer thickness by bypass channels in a wall. AB - When blood flows near a wall, red blood cells (RBCs) drift away from the wall and a cell-free layer (CFL) is formed adjacent to the wall. Controlling the CFL thickness is important for preventing adhesion of cells in the design of biomedical devices. In this study, a novel wall configuration with stenoses and bypass channels is proposed to increase the CFL thickness. We found that the presence of bypass channels modified the spatial distribution of cells and substantially increased the CFL downstream of the stenosis. A single-bypass geometry with 5% hematocrit (Hct) blood flow showed a 1.7MUm increase in CFL thickness compared to without the bypass. In the case of three bypass channels, a 3MUm increase in CFL thickness was observed. The CFL enhancement was observed up to 10% Hct, but no significant enhancement of CFL was indicated for 20% Hct blood flow. The mechanism of the CFL enhancement was investigated using a numerical simulation of the flow field. The results showed that the distance between each streamline and the corner of the stenosis compared with size of RBC was important parameter in regulating CFL thickness. These results show the potential of the proposed mechanism to prevent adhesion of cells to biomedical devices. PMID- 26803338 TI - An integrative modeling approach for the efficient estimation of cross sectional tibial stresses during locomotion. AB - The purpose of this research was to utilize a series of models to estimate the stress in a cross section of the tibia, located 62% from the proximal end, during walking. Twenty-eight male, active duty soldiers walked on an instrumented treadmill while external force data and kinematics were recorded. A rigid body model was used to estimate joint moments and reaction forces. A musculoskeletal model was used to gather muscle length, muscle velocity, moment arm and orientation information. Optimization procedures were used to estimate muscle forces and finally internal bone forces and moments were applied to an inhomogeneous, subject specific bone model obtained from CT scans to estimate stress in the bone cross section. Validity was assessed by comparison to stresses calculated from strain gage data in the literature and sensitivity was investigated using two simplified versions of the bone model-a homogeneous model and an ellipse approximation. Peak compressive stress occurred on the posterior aspect of the cross section (-47.5 +/- 14.9 MPa). Peak tensile stress occurred on the anterior aspect (27.0 +/- 11.7 MPa) while the location of peak shear was variable between subjects (7.2 +/- 2.4 MPa). Peak compressive, tensile and shear stresses were within 0.52 MPa, 0.36 MPa and 3.02 MPa respectively of those calculated from the converted strain gage data. Peak values from a inhomogeneous model of the bone correlated well with homogeneous model (normal: 0.99; shear: 0.94) as did the normal ellipse model (r=0.89-0.96). However, the relationship between shear stress in the inhomogeneous model and ellipse model was less accurate (r=0.64). The procedures detailed in this paper provide a non-invasive and relatively quick method of estimating cross sectional stress that holds promise for assessing injury and osteogenic stimulus in bone during normal physical activity. PMID- 26803339 TI - Uncertainty quantification in coronary blood flow simulations: Impact of geometry, boundary conditions and blood viscosity. AB - Computational fluid dynamic methods are currently being used clinically to simulate blood flow and pressure and predict the functional significance of atherosclerotic lesions in patient-specific models of the coronary arteries extracted from noninvasive coronary computed tomography angiography (cCTA) data. One such technology, FFRCT, or noninvasive fractional flow reserve derived from CT data, has demonstrated high diagnostic accuracy as compared to invasively measured fractional flow reserve (FFR) obtained with a pressure wire inserted in the coronary arteries during diagnostic cardiac catheterization. However, uncertainties in modeling as well as measurement results in differences between these predicted and measured hemodynamic indices. Uncertainty in modeling can manifest in two forms - anatomic uncertainty resulting in error of the reconstructed 3D model and physiologic uncertainty resulting in errors in boundary conditions or blood viscosity. We present a data-driven framework for modeling these uncertainties and study their impact on blood flow simulations. The incompressible Navier-Stokes equations are used to model blood flow and an adaptive stochastic collocation method is used to model uncertainty propagation in the Navier-Stokes equations. We perform uncertainty quantification in two geometries, an idealized stenosis model and a patient specific model. We show that uncertainty in minimum lumen diameter (MLD) has the largest impact on hemodynamic simulations, followed by boundary resistance, viscosity and lesion length. We show that near the diagnostic cutoff (FFRCT=0.8), the uncertainty due to the latter three variables are lower than measurement uncertainty, while the uncertainty due to MLD is only slightly higher than measurement uncertainty. We also show that uncertainties are not additive but only slightly higher than the highest single parameter uncertainty. The method presented here can be used to output interval estimates of hemodynamic indices and visualize patient-specific maps of sensitivities. PMID- 26803340 TI - Effects of Smoking Cessation on Presynaptic Dopamine Function of Addicted Male Smokers. AB - BACKGROUND: There is evidence of abnormal cerebral dopamine transmission in nicotine-dependent smokers, but it is unclear whether dopaminergic abnormalities are due to acute nicotine abuse or whether they persist with abstinence. We addressed this question by conducting longitudinal positron emission tomography (PET) examination of smokers before and after 3 months of abstinence. METHODS: We obtained baseline 6-[(18)F]fluoro-L-DOPA (FDOPA)-PET scans in 15 nonsmokers and 30 nicotine-dependent smokers, who either smoked as per their usual habit or were in acute withdrawal. All smokers then underwent cessation treatment, and successful abstainers were re-examined by FDOPA-PET after 3 months of abstinence (n = 15). Uptake of FDOPA was analyzed using a steady-state model yielding estimates of the dopamine synthesis capacity (K); the turnover of tracer dopamine formed in living brain (kloss); and the tracer distribution volume (Vd), which is an index of dopamine storage capacity. RESULTS: Compared with nonsmokers, K was 15% to 20% lower in the caudate nuclei of consuming smokers. Intraindividual comparisons of consumption and long-term abstinence revealed significant increases in K in the right dorsal and left ventral caudate nuclei. Relative to acute withdrawal, Vd significantly decreased in the right ventral and dorsal caudate after prolonged abstinence. Severity of nicotine dependence significantly correlated with dopamine synthesis capacity and dopamine turnover in the bilateral ventral putamen of consuming smokers. CONCLUSIONS: The results suggest a lower dopamine synthesis capacity in nicotine-dependent smokers that appears to normalize with abstinence. Further investigations are needed to clarify the role of dopamine in nicotine addiction to help develop smoking prevention and cessation treatments. PMID- 26803341 TI - Activation of Supraoptic Oxytocin Neurons by Secretin Facilitates Social Recognition. AB - BACKGROUND: Social recognition underlies social behavior in animals, and patients with psychiatric disorders associated with social deficits show abnormalities in social recognition. Oxytocin is implicated in social behavior and has received attention as an effective treatment for sociobehavioral deficits. Secretin receptor-deficient mice show deficits in social behavior. The relationship between oxytocin and secretin concerning social behavior remains to be determined. METHODS: Expression of c-Fos in oxytocin neurons and release of oxytocin from their dendrites after secretin application were investigated. Social recognition was examined after intracerebroventricular or local injection of secretin, oxytocin, or an oxytocin receptor antagonist in rats, oxytocin receptor-deficient mice, and secretin receptor-deficient mice. Electron and light microscopic immunohistochemical analysis was also performed to determine whether oxytocin neurons extend their dendrites into the medial amygdala. RESULTS: Supraoptic oxytocin neurons expressed the secretin receptor. Secretin activated supraoptic oxytocin neurons and facilitated oxytocin release from dendrites. Secretin increased acquisition of social recognition in an oxytocin receptor dependent manner. Local application of secretin into the supraoptic nucleus facilitated social recognition, and this facilitation was blocked by an oxytocin receptor antagonist injected into, but not outside of, the medial amygdala. In the medial amygdala, dendrite-like thick oxytocin processes were found to extend from the supraoptic nucleus. Furthermore, oxytocin treatment restored deficits of social recognition in secretin receptor-deficient mice. CONCLUSIONS: The results of our study demonstrate that secretin-induced dendritic oxytocin release from supraoptic neurons enhances social recognition. The newly defined secretin oxytocin system may lead to a possible treatment for social deficits. PMID- 26803342 TI - "ScreenIT": Computerized screening of swallowing, nutrition and distress in head and neck cancer patients during (chemo)radiotherapy. AB - BACKGROUND: In light of growing service demands, the use of computerized screening processes have been proposed to optimize patient triage and enhance the efficiency and synergy of multidisciplinary care practices. This study evaluated the accuracy of a novel system, ScreenIT, to detect swallowing, nutrition and distress status in HNC patients receiving (chemo)radiotherapy ([C]RT), and facilitate appropriate referrals for MDT management. MATERIALS AND METHODS: Patient-reported data obtained from ScreenIT was compared to blinded face-to-face assessment by speech pathology/dietetic clinicians across five domains: side effects, swallowing/oral intake, nutrition, distress, and need for supportive care services. Agreement was analysed using percent exact and close agreement (PEA/PCA) and kappa statistics. RESULTS: Clinically acceptable agreement (PEA/PCA 80% or higher) was achieved for the majority of domains. In areas of discordance, ScreenIT demonstrated a higher sensitivity to patient-perceived concerns, particularly regarding distress. Management pathways generated by ScreenIT initiated clinically appropriate referrals for high and medium-risk patients for swallowing/nutrition and distress. CONCLUSION: Findings suggest that ScreenIT may provide an effective and efficient means of monitoring swallowing, nutrition and distress status during (C)RT, and facilitate clinically appropriate prioritization of MDT supportive care intervention. PMID- 26803343 TI - Utility of a perioperative nutritional intervention on postoperative outcomes in high-risk head & neck cancer patients. AB - OBJECTIVES: Investigate both the utility and feasibility of perioperative nutritional supplementation with an arginine-enriched immunonutrition formula to high-risk head and neck cancer surgical patients and examine its effects on acute post-operative clinical outcomes. MATERIALS & METHODS: This prospective, non randomized, interventional cohort study compared high-risk head and neck cancer surgical patients who consumed a pre- and post-operative arginine-based nutritional supplement to those that did not. Outcome measures included post operative complications, length of hospitalization, readmission rates and measurement of nutritional biomarkers. RESULTS: 195 high-risk head and neck cancer surgical patients were enrolled. 59% of the patients used the nutritional supplement, 41% did not. Of the 80 patients who did not receive the immunonutrition formula, 38 (47.5%) experienced post-operative complications of all types as compared to 29 of the 115 (25.2%) patients who did consume the product (p=0.0021). Pharyngeal leaks or fistulas were the most common post operative complications in both groups and more common in patients who did not receive supplementation (p=0.007). Length of stay was on average 2.8 days longer in patients who did not have enhanced nutrition (p=0.02), while readmission rates between the two groups were similar (p=0.91). Measurements of nutritional biomarkers were not reported secondary to low collection rates. CONCLUSION: Enhanced perioperative nutrition may result in significant reductions of post operative fistula formations and decreased length of stay in a high-risk head and neck cancer population, even in the setting of poor compliance. The potential quality improvement in both patient care and healthcare cost is both real and significant. PMID- 26803344 TI - Shedding light on the dark side of identity: Introduction to the special issue. AB - The aim of this special issue is to shed light in the dark side of identity formation in adolescence and emerging adulthood, that is, to provide some understanding in what exactly can go wrong in identity development. After summarizing the recent developments in identity development literature, in this introduction the main findings of all thirteen empirical papers are summarized into three overarching themes: (1) lack of identity integration as a risk factor, (2) reconsideration of commitment as a sign of identity uncertainty, and (3) ruminative exploration as another risk factor undermining healthy identity development. Finally, given that all papers in this special issue are based on conference presentations at the 14th Biennial Conference of the European Association for Research on Adolescence (EARA), some more information on that conference is included in this introduction. PMID- 26803345 TI - Risk factors and outcomes of cutaneous melanoma in women less than 50 years of age. AB - BACKGROUND: Melanoma is the fifth most common cancer in the United States, with recent reports indicating increasing incidence among young women. OBJECTIVE: This study sought to investigate histopathology, staging, risk factors, and outcomes of cutaneous melanoma in women younger than 50 years. METHODS: All female patients aged up to 49 years with biopsy-proven diagnosis of melanoma between 1988 and 2012 were included. Patients with a follow-up of less than 2 years were excluded. RESULTS: A total of 462 patients were identified, with mean age of 34.7 years. Invasive melanoma was less common in women 19 years of age or younger (P < .0008). Positive sentinel node status (P < .008), recurrence rates, metastatic disease (P < .001), and death rates (P < .008) were higher for women ages 40 to 49 years. The 41 patients with a pregnancy-associated melanoma had a significantly worse prognosis in comparison with a control group of nonpregnant patients, with a 9-fold increase in recurrence (P < .001), 7-fold increase in metastasis (P = .03) and 5-fold increase in mortality (P = .06). LIMITATIONS: This was a retrospective study. CONCLUSION: The increasing incidence of melanoma for women younger than 50 years suggests that regular skin checks and self examinations are warranted. In addition, in women given the diagnosis of melanoma during or within 1 year after childbirth, regular follow-up and monitoring for recurrence are recommended. PMID- 26803346 TI - Perioral wrinkles are associated with female gender, aging, and smoking: Development of a gender-specific photonumeric scale. AB - BACKGROUND: Perioral wrinkling is commonly reported among older adults, but its objective evaluation and causes remain poorly understood. OBJECTIVE: We sought to develop a photonumeric scale for perioral wrinkling and to elucidate contributory lifestyle factors. METHODS: In this cross-sectional study, we recruited participants for facial photographs and a survey. A gender-specific photonumeric scale for perioral wrinkling was developed and used by 3 graders to evaluate participant photographs. Scores and survey responses were used to create a multiple regression model to predict perioral wrinkling. RESULTS: In all, 143 participants aged 21 to 91 years were enrolled. Intraclass correlation coefficient values for interrater and intrarater reliability were high (>0.8) across 2 trials and 3 graders. A multiple regression model for prediction of perioral wrinkling severity included age, gender, and years of smoking as variables. LIMITATIONS: The study was limited by sample size and a predominantly Caucasian study population. CONCLUSION: We created a photonumeric scale that accounts for gender differences in perioral wrinkling and highlighted contributory variables to photoaging in this anatomical location. PMID- 26803347 TI - Acral melanocytic lesions in the United States: Prevalence, awareness, and dermoscopic patterns in skin-of-color and non-Hispanic white patients. AB - BACKGROUND: Acral lentiginous melanoma has increased mortality compared with other melanoma subtypes and disproportionately affects ethnic minorities. Acral melanocytic lesions have not been well studied in diverse populations of the United States. OBJECTIVE: We sought to assess the prevalence, awareness, and dermoscopic patterns of acral melanocytic lesions in skin-of-color and non Hispanic white patients. METHODS: We prospectively examined the palms and soles of 1052 patients presenting to dermatology clinics in New York, NY, and Miami, FL, from October 2013 to April 2015. RESULTS: Acral melanocytic lesions were observed in 36% of our cohort. Skin-of-color patients were more likely to have acral melanocytic lesions than non-Hispanic white patients (P < .01). Acral melanocytic lesions correlated with increased mole counts, particularly on non Hispanic white patients. The majority of lesions demonstrated benign dermoscopic patterns. We observed 2 lesions with the parallel ridge pattern in our cohort, both found to be atypical nevi on biopsy specimen. Patients often lacked awareness of the presence of their lesions. LIMITATIONS: Interobserver variability in assessing dermoscopic patterns is a limitation. CONCLUSIONS: Melanocytic lesions of the palms and soles are common, particularly in a cohort of multiple ethnicities from the United States. Dermoscopy of acral lesions is an important clinical tool for diagnosis and management of these lesions. PMID- 26803348 TI - Guillain-Barre syndrome in a 7-month-old boy successfully applied plasma exchange. AB - Despite being the most common cause of acute flaccid paralysis in children Guillain-Barre syndrome has a low incidence under 18 years old, and is even rarer under the age of 2. Established treatment regimens include intravenous immunoglobulin and plasma exchange in older children and adults. However very limited data are available for the efficacy and safety of plasma exchange in infants younger than 12 month-old. This article presents the experience of plasma exchange in the case of 7-month-old boy diagnosed with Guillain-Barre syndrome. A 7-month-old boy was referred to the pediatric intensive care unit with a 10-day history of progressive weakness, feeding difficulty and constipation. He was diagnosed with axonal Guillain-Barre syndrome on the basis of clinical and electromyographical findings. The patient recovered fully with intravenous immunoglobulin and plasma exchange. Plasma exchange may be a safe option in the treatment in infants with Guillain-Barre syndrome as young as 7-month-age. PMID- 26803350 TI - 57-Year-Old Man With Hip Pain and Lytic Bone Lesions. PMID- 26803349 TI - Association of Mild Cognitive Impairment With Exposure to General Anesthesia for Surgical and Nonsurgical Procedures: A Population-Based Study. AB - OBJECTIVE: To examine whether exposure to general anesthesia for operations and procedures after the age of 40 years is associated with incident mild cognitive impairment (MCI) in elderly patients. PATIENTS AND METHODS: A population-based, prospective cohort of Olmsted County, Minnesota, residents aged 70 to 89 years at enrollment, underwent baseline and 15-month interval evaluations that included the Clinical Dementia Rating scale, a neurologic evaluation, and neuropsychological testing. Anesthesia records after the age of 40 years until last evaluation for MCI were abstracted. Proportional hazards regression, adjusting for other known MCI risk factors, was used to assess whether exposure to surgical general anesthesia after the age of 40 years is associated with the incidence of MCI. RESULTS: Of 1731 participants (mean age, 79 years), 536 (31.0%) developed MCI during a median follow-up of 4.8 years. Anesthesia exposure was not associated with MCI when analyzed as a dichotomous variable (any vs none; adjusted hazard ratio [HR], 1.07; 95% CI, 0.83-1.37; P=.61), the number of exposures (adjusted HR, 1.05; 95% CI, 0.78-1.42; adjusted HR, 1.12; 95% CI, 0.86 1.47; and adjusted HR, 1.02; 95% CI, 0.76-1.34, for 1, 2-3, and >=4 exposures compared with no exposure as the reference; P=.73), or the total cumulative duration of exposure (adjusted HR, 1.00; 95% CI, 0.98-1.01, per 60-minute increase; P=.83). In secondary sensitivity analyses, anesthesia after 60 years of age was associated with incident MCI (adjusted HR, 1.25; 95% CI, 1.02-1.55; P=.04), as was exposure in the previous 20 and 10 years. CONCLUSION: We found no significant association between cumulative exposure to surgical anesthesia after 40 years of age and MCI. However, these data do not exclude the possibility that anesthetic exposures occurring later in life may be associated with an increase in the rate of incident MCI. PMID- 26803351 TI - 47-Year-Old Woman With Chest Pain. PMID- 26803352 TI - 48-Year-Old Man With Dyspnea on Exertion. PMID- 26803353 TI - Description of the male, redescription of the female and 16S rDNA sequence of Ixodes aulacodi (Ixodidae). AB - Ixodes (Afrixodes) aulacodiArthur, 1956 is a poorly known species that has been recorded predominantly in the wet countries of western and central Africa, mainly associated to the greater cane rat Thryonomys swinderianus (Temmink). We herein redescribe the female, describe the male (ascribed to the species from specimens found in copula) and provide the 16S rDNA sequence. We also provide complete illustrations of the adults based on specimens found on greater cane rats in Ivory Coast. Ixodes aulacodi is included in the group of species of the subgenus Afrixodes that have horseshoe shaped anal groove, and which lack auriculae and cornua. The female is easily separated when compared with other species because of a unique combination of characters: All the coxae have internal spurs, coxa II has two external spurs, syncoxae are absent, and trochanters I-III have one spur each. The male has a notched hypostome and lacks syncoxae, auriculae and cornua. PMID- 26803354 TI - Hypoglycaemia and QT interval prolongation: Detection by simultaneous Holter and continuous glucose monitoring. AB - This study using simultaneous Holter and continuous glucose monitoring demonstrates that prolongation of QT interval can occur with hypoglycaemia in an ambulatory setting in people with type 1 and type 2 diabetes treated with insulin. This highlights the potential proarrhythmic harms associated with hypoglycaemia. PMID- 26803355 TI - Circulating adiponectin levels in type 2 diabetes mellitus patients with or without non-alcoholic fatty liver disease: Results of a small, open-label, randomized controlled intervention trial in a subgroup receiving short-term exenatide. AB - AIM: Diabetes mellitus type 2 (DMT2) and non-alcoholic fatty liver disease (NAFLD) are both characterized by decreased circulating adiponectin. Recently, glucagon-like peptide-1 receptor agonists have been shown to induce adiponectin's expression. However, their interaction on clinical grounds needs to be further elucidated. METHODS: DMT2 patients with abnormal aminotransferases were screened for NAFLD and subjected to liver biopsy (group A, n=17). A subgroup of patients (n=110), after assessed for eligibility criteria, was blindly randomized to receive either 6-month exenatide supplementation on glargine insulin (group B) or intense, self-regulated, insulin therapy alone (group C). RESULTS: Baseline patient characteristics: 49(38.6%) males, aged 63.1 +/- 7.5 years-old, BMI 32.9 +/- 4.9 kg/m(2), HbA1c 8.1 +/- 1.2% (65 +/- 14 mmol/mol), median ALT 23 U/L (range 5-126), AST 20 U/L (7-72). Group A had biopsy-proven NAFLD with a median Activity Score of 5 and fibrosis stage 3. Presence of NAFLD was accompanied by a significant decline in adiponectin (p<0.001), which was negatively correlated with the degree of ALT in all groups (Spearman's correlation, rs=-0.644, p<0.001). In the subgroup intervention trial, adiponectin was significantly raised in both groups B and C (t-Student for paired samples, p=0.001) by Delta=+24.2% (interquartile range 14.8-53.2%). This elevation was not associated with the type of intervention but with weight loss, glycemic control and reduction of C-reactive protein (one-way ANCOVA). CONCLUSION: Supplementation of exenatide to glargine insulin compared to standard insulin was: (i) effective in inducing weight loss, (ii) non-inferior in lowering HbA1c and (iii) non-inferior in increasing circulating adiponectin. Higher adiponectin was associated with lower ALT, suggesting a hepato-protective role for this cytokine. PMID- 26803356 TI - Lispro insulin in people with non-alcoholic liver cirrhosis and type 2 diabetes mellitus. AB - AIMS: To compare metabolic control under lispro and recombinant regular human insulin (RHI) in people with diet-unresponsive type 2 diabetes mellitus (T2DM) and compensated non-alcoholic liver disease (CLD). METHODS: 108 people with T2DM and CLD were randomly allocated to RHI or lispro according to a 12+12 week cross over protocol. A 1-week continuous glucose monitoring (CGM) session was performed at the end of each treatment period followed by a standard meal test with a 12IU lispro or RHI shot ahead. RESULTS: CGM showed higher glycemic excursions under RHI than under lispro (p<0.01) with lower glucose levels in the late post absorption phase (p<0.05) and even more during the night (p<0.01). Post-challenge incremental areas under the curve (DeltaAUC) were undistinguishable for insulin but lower for glucose, while insulin peaked higher and earlier and glycemic excursions were lower with lispro than with RHI (0.0540% TBSA. The most common burn sites were the upper extremities (31.57%), lower extremities (19.86%), and head and neck (28.83%). Most patients (581 (84.20%)) received water washing treatment on site immediately after exposure. The most common accompanying injuries included inhalation injury, ocular burns and digestive tract injury. The average hospital stay was 17.0+/ 23.1 days (range 1-333 days). Surgery was performed in 146 patients (21.16%), and the overall mortality rate was 0.58%. CONCLUSIONS: Chemical burns are preventable. The high morbidity of chemical burns in western Zhejiang Province is related to the industrial structure of the area. Governmental management in the fields of production, transportation, and utilization of chemicals could be improved. Workplaces have the responsibility to provide safe work environments and equipment, as well as occupational education and safety training for high risk work groups. PMID- 26803373 TI - Threshold age and burn size associated with poor outcomes in the elderly after burn injury. AB - Elderly burn care represents a vast challenge. The elderly are one of the most susceptible populations to burn injuries, but also one of the fastest growing demographics, indicating a substantial increase in patient numbers in the near future. Despite the need and importance of elderly burn care, survival of elderly burn patients is poor. Additionally, little is known about the responses of elderly patients after burn. One central question that has not been answered is what age defines an elderly patient. The current study was conducted to determine whether there is a cut-off age for elderly burn patients that is correlated with an increased risk for mortality and to determine the burn size in modern burn care that is associated with increased mortality. To answer these questions, we applied appropriate statistical analyses to the Ross Tilley Burn Centre and the Inflammatory and Host Response to Injury databases. We could not find a clear cut off age that differentiates or predicts between survival and death. Risk of death increased linearly with increasing age. Additionally, we found that the LD50 decreases from 45% total body surface area (TBSA) to 25% TBSA from the age of 55 years to the age of 70 years, indicating that even small burns lead to poor outcome in the elderly. We therefore concluded that age is not an ideal to predictor of burn outcome, but we strongly suggest that burn care providers be aware that if an elderly patient sustains even a 25% TBSA burn, the risk of mortality is 50% despite the implementation of modern protocolized burn care. PMID- 26803374 TI - [Effectiveness of implementing the reiki method to reduce the weaning failure. A clinical trial]. AB - INTRODUCTION: Admission to intensive care unit (ICU) is a difficult and stressful time for the patient, with the application of different techniques, such as intubation and ventilation support withdrawal or "weaning", which may fail due to anxiety. OBJECTIVES: To determine whether Reiki is useful in reducing weaning failure, as well as reducing the number of days of mechanical ventilation (MV), length of stay in ICU, amount of sedatives, amines, and antipsychotics. METHOD: Randomized clinical trial. SCOPE: ICU of a Level III University Hospital. POPULATION: ICU patients connected to Mechanical Ventilation for more than 48hours, with a signed informed consent. Patients in a terminal condition or potential organ donors were excluded. SAMPLE: 256 patients divided into two groups: intervention group (GI) and placebo (GP). The intervention involves the application of Reiki, and a simulated technique within the placebo group. An analysis was made of the absolute and relative frequencies, with a significance level of P<.05, 95% CI RESULTS: The percentage of failures at weaning was 9% in GI and 9.5% in GP (P=.42). The mean number of days on MV was 8.85 days for GI and 9.66 for the GP (P=.53). The mean dose of sedatives: GI 1078mg and 1491mg GP. The dose of Haloperidol was lower in the GI (5.30mg vs 16.81mg GP) (P=.03, 95% CI; 21.9 to -1.13). CONCLUSIONS: Reiki reduces the agitation of patients. A decrease was objectively observed in the number of days of Mechanical Ventilation, length of stay, lower doses of sedatives, and a slight decrease in the weaning failure in the GI. No statistically significant difference was found in the main variable. PMID- 26803375 TI - [Analysis of the intensity of professional collaboration among nurses in a critical care area]. AB - OBJECTIVE/S: To analyse the intensity of professional collaboration (IPC) between the nurses in a multidisciplinary critical area (CA) and the relationship with the workplace "intensive care unit (ICU) and special hospitalisation area (SHA)", educational level, age, and years of professional activity in CA. METHOD: A cross sectional descriptive study was conducted with 57 nurses from CA, recording socio demographic data: age, educational level, speciality titles, years of professional activity and workday type, years of professional activity in the CA, and involvement in scientific works. Tool: Intensity of Inter-professional Collaboration Questionnaire. STATISTICAL ANALYSIS: SPSS 20.0. RESULTS: The study included a total of 47 nurses (ICU/SHA), with a mean age of 35.91 (9.59) years. Almost three-quarters (74.46%) were nursing graduates with a posgraduate in ICU. Median and interquartile range of professional experience was 14 and 14.50 years, respectively, and years working in CA was 8.50 and 16 years, respectively. Just over half of them (51.10%) worked part-time, and 61.70% participated in scientific works. The mean IPC score was 61.68 (6.84), with 57.40% providing values of high IPC. The relationship between the workplace (ICU/SHA) and educational level with IPC was not statistically significant (p>.05). There are statistical significant differences between IPC with age and years of professional activity in CA (p<.05). CONCLUSIONS: The present study demonstrates the existence of good IPC in the CA. Younger nurses obtain a better IPC score, as well as nurses who have been working for less time in CA. Nurses with a Degree or Masters have a higher level of IPC than the rest, as well as nurses who perform professional activity combining ICU and SHA. PMID- 26803376 TI - [A first step towards safer sedation and analgesia: A systematic evaluation of outcomes and level of sedation and analgesia in the mechanically ventilated critically ill patient]. AB - INTRODUCTION: Safe analgesia and sedation strategies are necessary in order to avoid under or over sedation, as well as improving the comfort and safety of critical care patients. OBJECTIVES: To compare and contrast a multidisciplinary protocol of systematic evaluation and management of analgesia and sedation in a group of critical care patients on mechanical ventilation with the usual procedures. MATERIALS AND METHODS: A cohort study with contemporary series was conducted in a tertiary care medical-surgical ICU February to November during 2013 and 2014. The inclusion criteria were mechanical ventilation >= 24h and use of sedation by continuous infusion. Sedation was monitored using the Richmond agitation-sedation scale or bispectral index, and analgesia were measured using the numeric rating scale, or behavioural indicators of pain scale. The study variables included; mechanical ventilation time, weaning time, ventilation support time, artificial airway time, continuous sedative infusion time, daily dose and frequency of analgesic and sedative drug use, hospital stay, and ICU and hospital mortality, Richmond agitation-sedation scale, bispectral index, numeric rating scale, and behavioural indicators of pain scale measurements. Kruskal Wallis and Chi2, and a significance of p<.05 were used. RESULTS: The study included 153 admissions, 75 pre-intervention and 78 post-intervention, with a mean age of 55.7+/-13 years old, and 67% men. Both groups showed similarities in age, reason for admission, and APACHE. There were non-significant decreases in mechanical ventilation time 4 (1.4-9.2) and 3.2 (1.4-8.1) days, respectively; p= 0.7, continuous sedative infusion time 6 (3-11) and 5 (3-11) days; p= 0.9, length of hospital stay 29 (18-52); 25 (14-41) days; p= 0.1, ICU mortality (8 vs. 5%; p= 0.4), and hospital mortality (10.6 vs. 9.4%: p= 0.8). Daily doses of midazolam and remifentanil decreased 347 (227-479) mg/day; 261 (159-358) mg/day; p= 0.02 and 2175 (1427-3285) mcg/day; 1500 (715-2740) mcg/day; p= 0.02, respectively. There were increases in the use of remifentanil (32% vs. 51%; p= 0.01), dexmedetomidine (0 vs.6%; p= 0.02), dexketoprofen (60 vs. 76%; p= 0.03), and haloperidol (15 vs.28%; p= 0.04). The use of morphine decreased (71 vs. 54%; p= 0.03). There was an increase in the number of measurements and Richmond agitation sedation scale scores 6 (3-17); 21 (9-39); p< 0.0001, behavioural indicators of pain scale 6 (3-18); 19(8-33); p< 0.001 and numeric rating scale 4 (2-6); 8 (6 17); p< 0.0001. CONCLUSIONS: The implementation of a multidisciplinary protocol of systematic evaluation of analgesia and sedation management achieved an improvement in monitoring and adequacy of dose to patient needs, leading to improved outcomes. PMID- 26803377 TI - A systematic review of interventions to reduce hospitalisation in Parkinson's disease. AB - The neurodegenerative process in Parkinson's disease (PD) results in a relentless progression of motor and non-motor symptoms. Affected individuals are frequently hospitalised for complications of the disease including falls, fractures, infections, and neuropsychiatric symptoms. When admitted to hospital, inpatient care is often suboptimal as it focusses on the primary cause of admission, and is associated with poor patient outcomes and significant healthcare costs. AIM: To review existing literature for evidence-based interventions aimed at reducing hospital admissions in PD. METHODS: Electronic literature search in EMBASE, MEDLINE and CINAHL databases for studies evaluating interventions to reduce hospital admissions in PD. We included publications with full abstracts, published in the English language and addressing interventions to reduce hospital admissions in PD. RESULTS: To date there are no randomised controlled trials addressing the topic. We identified nine relevant retrospective studies. Results from these studies suggest an association between frequent neurologist consultations, open access clinics, and medication compliance with a reduction in PD hospital admissions and emergency room visits. CONCLUSION: This systematic review highlights the lack of robust evidence for measures aimed at reducing hospital admissions in people with PD. Future prospective studies are required to evaluate the effectiveness of proposed interventions. PMID- 26803378 TI - HIV-1 Envelope Under Attack. AB - The human immunodeficiency virus type 1 (HIV-1) envelope (Env) plays a critical role in viral replication and represents a potential target for host antiviral factors. Recent work by Tada and colleagues identifies membrane-associated-RING CH8 (MARCH8) as a potent anti-HIV factor blocking virion incorporation of Env. Thus, MARCH8 joins a growing list of host factors attacking HIV-1 Env. PMID- 26803379 TI - It's Gettin' Hot in Here: Breeding Robust Yeast Starter Cultures for Cocoa Fermentation. AB - Cocoa beans have to undergo post-harvest fermentation and drying to develop the typical 'cocoa flavor' associated with chocolate. Yeasts play a pivotal role during the fermentation but are generally outcompeted early in the process. Meersman and colleagues describe an elegant breeding-based approach to generate robust yeast starter cultures for cocoa fermentation. PMID- 26803381 TI - Prevalence and Correlates of Post-traumatic Stress Disorder in Adults With Congenital Heart Disease. AB - Post-traumatic stress disorder (PTSD) is associated with adverse outcomes and increased mortality in cardiac patients. No studies have examined PTSD in the adult congenital heart disease (ACHD) population. The objectives of this study were to assess the prevalence of self-reported symptoms of PTSD in patients with ACHD and explore potential associated factors. Patients were enrolled from an outpatient ACHD clinic and completed several validated measures including the Impact of Event Scale-Revised, PTSD Checklist-Civilian Version, and the Hospital Anxiety and Depression Scale. Clinical data were abstracted through medical data review. A total of 134 participants (mean age 34.6 +/- 10.6; 46% men) were enrolled. Of the 127 participants who completed the Impact of Event Scale Revised, 14 (11%) met criteria for elevated PTSD symptoms specifically related to their congenital heart disease or treatment. Of the 134 patients who completed PTSD Checklist-Civilian Version, 27 (21%) met criteria for global PTSD symptoms. In univariate analyses, patients with congenital heart disease-specific PTSD had their most recent cardiac surgery at an earlier year (p = 0.008), were less likely to have attended college (p = 0.04), had higher rates of stroke or transient ischemic attack (p = 0.03), and reported greater depressive symptoms on the Hospital Anxiety and Depression Scale (7 vs 2, p <0.001). In multivariable analysis, the 2 factors most strongly associated with PTSD were depressive symptoms (p <0.001) and year of most recent cardiac surgery (p <0.03). In conclusion, PTSD is present in 11% to 21% of subjects seen at a tertiary referral center for ACHD. The high prevalence of PTSD in this complex group of patients has important implications for the medical and psychosocial management of this growing population. PMID- 26803380 TI - The single breath nitrogen test and mortality--A 38 years follow up. AB - BACKGROUND: Spirometry data predict mortality, but are less sensitive to detect dysfunction in small airways as compared to the slope of phase III (the N2 slope) of the single breath nitrogen test. The association between the N2 slope and mortality has been studied with conflicting results. In the present study the prognostic importance of the N2 slope was tested taking spirometry variables into account. METHODS: A systematic general population sample of 595 middle-aged men had a baseline investigation with lung function tests including spirometry and the N2 slope. Age, smoking, and anthropometry variables were registered. The cohort was followed up regarding survival for 38 years. RESULTS: The sample was subdivided by tertiles of the N2 slope. A proportional hazards regression analysis was performed for each group of covariates: anthropometric, smoking variables, and spirometry variables, after accounting for age. Covariates with significant impact on mortality and the highest chi-square levels were smoking habit score and forced expired volume in 1 s corrected for height. These variables, in addition to age and the N2 tertiles were entered into a final proportional hazards regression analysis. In this multivariate model, mortality was significantly related to age (p < .0001), smoking habit score (p < .0001) and the N2 tertiles (p = .0004), but not to FEV1 when N2 slope was allowed for in the model. CONCLUSIONS: Dysfunction in small airways as measured by the N2 slope is significantly associated with overall mortality in middle-aged men, and outrivals spirometry as a predictor in multivariate analysis. PMID- 26803382 TI - Effect of Coronary Artery Bypass Grafting on Left Ventricular Ejection Fraction in Men Eligible for Implantable Cardioverter-Defibrillator. AB - Implantable cardioverter-defibrillator (ICD) therapy for primary prevention of sudden cardiac death is not routinely recommended within 90 days of coronary artery bypass grafting (CABG) because of the possibility of an improvement in left ventricular ejection fraction (EF) to>35% after revascularization. We sought to determine the incidence and predictors of EF improvement to >35% after isolated CABG in patients who had a preoperative EF <=35%. We studied 375 patients who underwent CABG at a tertiary institution and had an echocardiogram preoperatively and postoperatively. Of these, 74 patients (20%) with a preoperative EF <=35% were included in this analysis. Improvement in EF was defined as postoperative EF >35%. In the overall study population (n = 74), mean EF improved from 28 +/- 6% preoperatively to 36 +/- 12% postoperatively (p <0.0001). A total of 38 patients (51%) had postoperative improvement in EF to >35% (mean EF in these patients increased from 30 +/- 5% to 46 +/- 8%; p <0.0001). Patients with EF improvement had a higher preoperative EF than those with no improvement (30 +/- 5% vs 26 +/- 7%, p <0.005). Improvement in EF was 5 times more likely in patients with preoperative EF 26% to 35% (odds ratio 4.95, 95% CI 1.73 to 14.1; p = 0.003) than those with preoperative EF <=25%. Other clinical characteristics were not significantly different between patients with versus without EF improvement. In conclusion, more than half of the ICD-eligible patients who underwent CABG improved their EF to >35% after surgery and became ineligible for a primary prevention ICD. EF improvement was unlikely in patients with preoperative EF <25%. PMID- 26803383 TI - Value of Coronary Computed Tomography Angiography in Tailoring Aspirin Therapy for Primary Prevention of Atherosclerotic Events in Patients at High Risk With Diabetes Mellitus. AB - Aspirin use for primary prevention in patients at high risk with diabetes mellitus (DM) is often recommended under the assumption that most patients with DM have coronary artery disease (CAD). However, not all patients may have CAD. The present study evaluated, in 425 patients at high risk with DM (without chest pain syndrome or a history of cardiac disease), the prevalence of CAD on coronary computed tomography angiography (CTA). Moreover, the association between the presence and number of traditional cardiovascular (CV) risk factors and CAD (on coronary CTA) was evaluated. The median coronary artery calcium score was 29 (interquartile range 0 to 298). On coronary CTA, 116 patients (27%) had no CAD (defined as <30% stenosis). Of the 309 patients (73%) with any CAD (>=30% stenosis), 35% had obstructive CAD (>=50% stenosis). The number of traditional CV risk factors was not associated with the presence of any CAD (>=30% stenosis; p = 0.18) or obstructive CAD (>=50% stenosis; p = 0.13). Hypertension was the only traditional CV risk factor associated with a higher frequency of any CAD (>=30% stenosis; odds ratio = 2.21, 95% CI 1.43 to 3.41, p <0.001) and obstructive CAD (>=50% stenosis; odds ratio 2.03, 95% CI 1.33 to 3.11, p = 0.001). In conclusion, in patients at high risk with DM without chest pain syndrome, any CAD was ruled out by coronary CTA in 27%, whereas 65% of the patients did not have obstructive CAD. The number of CV risk factors was not associated with the presence of CAD. Hypertension was the only traditional CV risk factor that was associated with a higher frequency of CAD. These observations support potential use of coronary CTA to tailor aspirin therapy in patients at high risk with DM. PMID- 26803384 TI - Meta-Analysis of Efficacy and Safety of New Oral Anticoagulants Compared With Uninterrupted Vitamin K Antagonists in Patients Undergoing Catheter Ablation for Atrial Fibrillation. AB - Anticoagulation in catheter ablation (CA) of atrial fibrillation (AF) is of paramount importance for prevention of thromboembolic events, and recent studies favor uninterrupted vitamin K antagonists (VKAs). We aimed to compare the efficacy and safety of new oral anticoagulants (NOACs) to uninterrupted VKAs for anticoagulation in CA by performing a meta-analysis. PubMed, EMBASE, the Cochrane Library, and Clinicaltrials.gov databases were searched for studies comparing NOACs with uninterrupted VKAs in patients who underwent CA for AF from January 1, 2000, to August 31, 2015. Odds ratio (OR) and Peto's OR (POR) were used to report for event rates >1% and <1%, respectively. A total of 11,686 patients with AF who underwent CA in 25 studies were included in this analysis. There was no significant difference between NOACs and uninterrupted VKAs in occurrence of stroke or transient ischemic attacks (POR 1.35, 95% CI 0.62 to 2.94) and major bleeding (POR 0.87, 95% CI 0.58 to 1.31), which were consistent in subgroup analysis of interrupted and uninterrupted NOACs. A lower risk of minor bleeding was observed with NOACs (OR 0.80, 95% CI 0.65 to 1.00), and no major differences were observed for the risk of thromboembolic events, cardiac tamponade or pericardial effusion requiring drainage, and groin hematoma. NOACs, whether interrupted preprocedure or not, were associated with equal rates of stroke or TIA and major bleeding complications and less risk of minor bleeding compared with uninterrupted VKAs in CA for AF. PMID- 26803385 TI - Atrial Fibrillation in Infective Endocarditis. PMID- 26803386 TI - Entry-Level Competencies Required of Primary Care Nurse Practitioners Providing HIV Specialty Care: A National Practice Validation Study. AB - In the United States, only 30% of HIV-infected persons are diagnosed, engaged in care, provided antiretroviral therapy, and virologically suppressed. Competent HIV care providers are needed to achieve optimal clinical outcomes for all people living with HIV, but 69% of Ryan White Clinics in the United States report difficulty recruiting HIV clinicians, and one in three current HIV specialty physicians are expected to retire in the next decade. Nurse practitioners who specialize in HIV and have caseloads with large numbers of HIV-infected patients have care outcomes that are equal to or better than that provided by physicians, especially generalist non-HIV specialist physicians. We designed a national practice validation study to help prepare the next generation of primary care nurse practitioners who desire to specialize in HIV. This manuscript reports the results of the national study and identifies entry-level competencies for entry level primary care nurse practitioners specializing in HIV. PMID- 26803387 TI - MicroRNA-92 expression may be associated with reduced estrogen receptor beta1 mRNA levels in cervical portion of uterosacral ligaments in women with pelvic organ prolapse. AB - OBJECTIVE: This study examined microRNA-92 (miR-92) expression level in relation to the mRNA level of its potential target gene, estrogen receptor beta1 (ERbeta1), in female patients diagnosed with pelvic organ prolapse (POP). STUDY DESIGN: Between July 2012 and September 2014, a total of 104 patients were recruited at the First Affiliated Hospital of Sun Yat-sen University, which included 56 POP patients and 48 non-POP control subjects. Based on POP-Q score, the POP patients were further categorized into POP II and POP III groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify miR-92 expression level. ERbeta1 tissue expression was measured by western blot and immunohistochemistry (IHC) methods. SPSS 19.0 software was used for statistical analysis. RESULTS: No remarkable differences were observed between the POP group and non-POP group, and between the POP II and POP III groups, with respect to age, body mass index (BMI), parity, menopause status, and family history of POP. The expression level of miR-92 in the POP group was dramatically higher than the non-POP group (P<0.05). Consistent with the disease status, miR 92 expression level in POP III group was markedly higher than the POP II group (P<0.05). Western blot analysis revealed significantly reduced levels of ERbeta1 in the POP group compared to the non-POP group, with similar results obtained between the POP III and POP II groups (all P<0.05). IHC results showed ERbeta1 staining mainly in the nucleus and semi-quantitative measurements, expressed as positive expression rate, revealed that ERbeta1 level in the POP group was clearly lower than non-POP group. Finally, statistical analysis of IHC results from uterosacral ligament tissue showed inverse correlation between miR-92 and ERbeta1 expression levels in POP patients (P<0.05). CONCLUSIONS: Our results revealed increased miR-92 expression and decreased ERbeta1 level in uterosacral ligaments of women diagnosed with POP, compared to non-POP subjects POP III patients exhibited more severe changes than POP II patients. Further, ERbeta1expression is inversely correlated to miR-92 expression. Taken together, our results suggest that miR-92 and ERbeta1 expression levels may be used as reliable diagnostic markers for assessing the severity of POP. PMID- 26803388 TI - Elastosonographic evaluation of patients with a sonographic finding of thickened endometrium. AB - OBJECTIVE: To evaluate if elastosonography of the endometrium can differ between normal endometrial tissue and abnormal pathology. STUDY DESIGN: One hundred and six women with a sonographic finding of thickened endometrium were enrolled in this study. All patients underwent B-mode scanning and elastosonography, performed by the same operator who was blinded to the study design. After sonographic evaluation, all patients underwent endometrial tissue sampling via dilatation and curettage. Histopathological results indicated that 22 patients had endometrial hyperplasia, 20 patients had endometrial polyps, and 64 patients had normal pathology results, with or without abnormal uterine bleeding. Groups were formed according to histopathological results, and ultrasonographic findings (strain ratio, endometrial thickness) were compared. RESULTS: Median age was 46 [interquartile range (IQR) 4] years, 37 (IQR 10) years and 36 (IQR 10) years for the endometrial hyperplasia, endometrial polyps and normal pathology groups, respectively. Median age of the endometrial hyperplasia group was significantly higher compared with the endometrial polyps and normal pathology groups (p<0.001). Median parity was 3 (IQR 2), 2 (IQR 1) and 3 (IQR 1) for the endometrial hyperplasia, endometrial polyps and normal pathology groups, respectively; differences between the groups were not significant (p=0.102). No differences were found between the groups in terms of endometrial thickness (p>0.05). When elastosonographic strain (B/A) ratios were compared between the groups, the endometrial hyperplasia and endometrial polyps groups had significantly lower B/A ratios (higher elasticity) than the normal pathology group (p<0.001). There was no significant difference in B/A ratios between the endometrial hyperplasia and endometrial polyps groups (p>0.05). CONCLUSION: The elasticity of endometrial tissue, measured non-invasively via elastosonography, was similar in women with endometrial polyps and endometrial hyperplasia, but differed significantly compared with women with normal pathology who had a sonographic finding of thickened endometrium and abnormal bleeding as the presenting complaint. According to these results, elastosonography cannot be used as a diagnostic tool to differentiate between endometrial hyperplasia and endometrial polyps. However, elastosonography can be used to differentiate between pathological endometrial changes and normal endometrium in patients presenting with a sonographic finding of thickened endometrium. PMID- 26803390 TI - Predictive Value of Conventional Ultrasound and Contrast-Enhanced Ultrasound in Early Recurrence of Hepatocellular Carcinoma after Surgical Resection. AB - The goals of the work described here were to study the pre-operative risk factors associated with early recurrence (ER) of hepatocellular carcinoma (HCC) after surgical resection and discuss the value of conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) in predicting ER of HCC, so as to provide more information for optimizing clinical treatment and improving prognosis. A retrospective analysis was conducted on 59 patients who underwent both US and CEUS examinations pre-operatively and surgical resection for HCC between December 2010 and January 2014 in our hospital. The patients' clinical data, laboratory examination data and ultrasonic imaging diagnostic data were collected. Univariate analysis and logistic regression analysis were performed to determine the independent risk factors for ER of HCC after surgical resection. Diagnostic values of independent risk factors in predicting ER were further evaluated. The 59 patients were divided into the ER group (27 cases) and ER-free group (32 cases). There were no significant differences in age and sex between the two groups (p > 0.05). Univariate analysis revealed that differences in pre-operative serum alpha-fetoprotein level >=400 ng/mL (p = 0.008), tumor diameter >=5 cm (p = 0.012), macroscopic vascular invasion (p = 0.040), "fast wash-out" enhancement pattern (p = 0.006) and inhomogeneous distribution of contrast agent (p = 0.031) statistically significantly differed between the two groups. Logistic regression analysis indicated that pre-operative serum AFP level >=400 ng/mL (p = 0.024), tumor diameter >=5 cm (p = 0.042) and "fast wash-out" enhancement pattern (p = 0.009) were independent risk factors for ER of HCC; macrovascular invasion (p = 0.095) and inhomogeneous distribution of contrast agent (p = 0.628) did not statistically significantly differ between two groups (p = 0.628). Predictive values of the independent risk factors were further evaluated. The sensitivity of a "fast wash-out" enhancement pattern in predicting ER of HCC post-operatively did not statistically differ from that of tumor diameter >=5 cm (p > 0.05), whereas it was significantly higher than the sensitivities of the other predictive indexes (p < 0.05). A pre-operative serum alpha-fetoprotein level >=400 ng/mL, tumor diameter >=5 cm and "fast wash-out" enhancement pattern are independent risk factors for ER of HCC after surgical resection. In addition, the "fast wash-out" enhancement pattern could probably be used to screen populations at high risk of recurrence owing to its high sensitivity in predicting ER of HCC post-operatively. All these findings provide beneficial information for management of HCC. PMID- 26803389 TI - Enhancement of Small Molecule Delivery by Pulsed High-Intensity Focused Ultrasound: A Parameter Exploration. AB - Chemotherapeutic drug delivery is often ineffective within solid tumors, but increasing the drug dose would result in systemic toxicity. The use of high intensity focused ultrasound (HIFU) has the potential to enhance penetration of small molecules. However, operation parameters need to be optimized before the use of chemotherapeutic drugs in vivo and translation to clinical trials. In this study, the effects of pulsed HIFU (pHIFU) parameters (spatial-average pulse average intensity, duty factor and pulse repetition frequency) on the penetration as well as content of small molecules were evaluated in ex vivo porcine kidneys. Specific HIFU parameters resulted in more than 40 times greater Evans blue content and 3.5 times the penetration depth compared with untreated samples. When selected parameters were applied to porcine kidneys in vivo, a 2.3-fold increase in concentration was obtained after a 2-min exposure to pHIFU. Pulsed HIFU has been found to be an effective modality to enhance both the concentration and penetration depth of small molecules in tissue using the optimized HIFU parameters. Although, performed in normal tissue, this study has the promise of translation into tumor tissue. PMID- 26803391 TI - Improvement of Shear Wave Motion Detection Using Harmonic Imaging in Healthy Human Liver. AB - Quantification of liver elasticity is a major application of shear wave elasticity imaging (SWEI) to non-invasive assessment of liver fibrosis stages. SWEI measurements can be highly affected by ultrasound image quality. Ultrasound harmonic imaging has exhibited a significant improvement in ultrasound image quality as well as for SWEI measurements. This was previously illustrated in cardiac SWEI. The purpose of this study was to evaluate liver shear wave particle displacement detection and shear wave velocity (SWV) measurements with fundamental and filter-based harmonic ultrasound imaging. In a cohort of 17 patients with no history of liver disease, a 2.9-fold increase in maximum shear wave displacement, a 0.11 m/s decrease in the overall interquartile range and median SWV and a 17.6% increase in the success rate of SWV measurements were obtained when filter-based harmonic imaging was used instead of fundamental imaging. PMID- 26803392 TI - 'Mum's the word': Predictors and outcomes of weight concerns in pre-adolescent and early adolescent girls. AB - Predictors and outcomes of weight concerns in pre-adolescent and adolescent girls are well known, but few models have incorporated concerns reported directly by mothers as a predictor, and both eating and exercise outcomes. Using questionnaires, a comprehensive model of 232 pre-adolescent and early adolescent girls' weight concerns, eating restraint, and exercise behavior was tested. Structural equation modeling showed that daughters' weight concerns were predicted primarily by their perceptions of their mothers' concerns about the daughters' weight, as well as by daughters' BMI, appearance conversations with friends, and perceived media pressure. Mothers' concerns with their daughters' weight were indirectly associated with daughters' own concerns, via the daughters' perceptions of their mothers' concerns. Daughters' concerns with their weight were a strong predictor of eating restraint, but not exercise behavior. PMID- 26803393 TI - Hands typing what hands do: Action-semantic integration dynamics throughout written verb production. AB - Processing action verbs, in general, and manual action verbs, in particular, involves activations in gross and hand-specific motor networks, respectively. While this is well established for receptive language processes, no study has explored action-semantic integration during written production. Moreover, little is known about how such crosstalk unfolds from motor planning to execution. Here we address both issues through our novel "action semantics in typing" paradigm, which allows to time keystroke operations during word typing. Specifically, we created a primed-verb-copying task involving manual action verbs, non-manual action verbs, and non-action verbs. Motor planning processes were indexed by first-letter lag (the lapse between target onset and first keystroke), whereas execution dynamics were assessed considering whole-word lag (the lapse between first and last keystroke). Each phase was differently delayed by action verbs. When these were processed for over one second, interference was strong and magnified by effector compatibility during programming, but weak and effector blind during execution. Instead, when they were processed for less than 900ms, interference was reduced by effector compatibility during programming and it faded during execution. Finally, typing was facilitated by prime-target congruency, irrespective of the verbs' motor content. Thus, action-verb semantics seems to extend beyond its embodied foundations, involving conceptual dynamics not tapped by classical reaction-time measures. These findings are compatible with non-radical models of language embodiment and with predictions of event coding theory. PMID- 26803394 TI - Other-self confusions in action memory: The role of motor processes. AB - People can come to falsely remember performing actions that they have not actually performed. Common accounts of such false action memories have invoked source confusion from the overlap of sensory features but largely ignored the role of motor processes. We addressed this lacuna with a paradigm in which participants first perform (vs. do not perform) actions and then observe another person performing some of the non-performed actions. In this paradigm, observation of videos showing another's actions can later induce false self attributions of these actions, the observation-inflation effect. Contrary to a sensory-feature account but consistent with a motor-simulation account, we found the effect even with perceptually impoverished action videos in which the majority of sensory features is absent, but motion cues are preserved (Experiment 1). We then created conditions during action observation that should (vs. should not) impede motor simulation. As predicted we found that the effect of observation was reduced when participants executed movements that were incongruent (vs. congruent) with the observed actions (Experiment 2). We discuss the processes that can produce associations of self with observed others' actions and later affect observers' action memory. PMID- 26803395 TI - Nor-hopanes from Zanha africana root bark with toxicity to bruchid beetles. AB - Zanha africana (Radlk.) Exell (Sapindaceae) root bark is used by farmers throughout sub-Saharan Africa to protect stored grain from bruchid beetles, such as Callosobruchus maculatus. Chloroform, methanol and water extracts of Z. africana root bark inhibited oviposition and caused significantly higher mortality of C. maculatus at a rate of application equivalent to that applied by farmers compared to control insects. The chloroform extract contained nor-hopanes rarely found in plants of which seven were isolated, one of which was previously known. Two of the most abundant nor-hopanes 3beta,6beta-dihydroxy-7beta-[(4 hydroxybenzoyl)oxy]-21alphaH-24-norhopa-4(23),22(29)-diene and 3beta,6beta dihydroxy-7beta-[(4-hydroxybenzoyl)oxy]-24-norhopa-4(23),17(21)-diene were toxic to and reduced oviposition of C. maculatus in a dose dependent manner. Z. africana root bark is rich in insecticidal compounds that account for its effective use by smallholder farmers as an alternative to conventional insecticides. PMID- 26803396 TI - Arbuscular mycorrhizal fungal responses to abiotic stresses: A review. AB - The majority of plants live in close collaboration with a diversity of soil organisms among which arbuscular mycorrhizal fungi (AMF) play an essential role. Mycorrhizal symbioses contribute to plant growth and plant protection against various environmental stresses. Whereas the resistance mechanisms induced in mycorrhizal plants after exposure to abiotic stresses, such as drought, salinity and pollution, are well documented, the knowledge about the stress tolerance mechanisms implemented by the AMF themselves is limited. This review provides an overview of the impacts of various abiotic stresses (pollution, salinity, drought, extreme temperatures, CO2, calcareous, acidity) on biodiversity, abundance and development of AMF and examines the morphological, biochemical and molecular mechanisms implemented by AMF to survive in the presence of these stresses. PMID- 26803397 TI - Cross-trial prediction of treatment outcome in depression: a machine learning approach. AB - BACKGROUND: Antidepressant treatment efficacy is low, but might be improved by matching patients to interventions. At present, clinicians have no empirically validated mechanisms to assess whether a patient with depression will respond to a specific antidepressant. We aimed to develop an algorithm to assess whether patients will achieve symptomatic remission from a 12-week course of citalopram. METHODS: We used patient-reported data from patients with depression (n=4041, with 1949 completers) from level 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D; ClinicalTrials.gov, number NCT00021528) to identify variables that were most predictive of treatment outcome, and used these variables to train a machine-learning model to predict clinical remission. We externally validated the model in the escitalopram treatment group (n=151) of an independent clinical trial (Combining Medications to Enhance Depression Outcomes [COMED]; ClinicalTrials.gov, number NCT00590863). FINDINGS: We identified 25 variables that were most predictive of treatment outcome from 164 patient reportable variables, and used these to train the model. The model was internally cross-validated, and predicted outcomes in the STAR*D cohort with accuracy significantly above chance (64.6% [SD 3.2]; p<0.0001). The model was externally validated in the escitalopram treatment group (N=151) of COMED (accuracy 59.6%, p=0.043). The model also performed significantly above chance in a combined escitalopram-buproprion treatment group in COMED (n=134; accuracy 59.7%, p=0.023), but not in a combined venlafaxine-mirtazapine group (n=140; accuracy 51.4%, p=0.53), suggesting specificity of the model to underlying mechanisms. INTERPRETATION: Building statistical models by mining existing clinical trial data can enable prospective identification of patients who are likely to respond to a specific antidepressant. FUNDING: Yale University. PMID- 26803398 TI - Predicting treatment outcome in depression: so far, so good. PMID- 26803399 TI - Examining the relationship between personality and affect-related attributes and adolescents' intentions to try smoking using the Substance Use Risk Profile Scale. AB - Assessments of adolescents' smoking intentions indicate that many are susceptible to smoking initiation because they do not have resolute intentions to abstain from trying smoking in the future. Although researchers have developed personality and affect-related risk factor profiles to understand risk for the initiation of substance use and abuse (e.g., alcohol), few have examined the extent to which these risk factors are related to the tobacco use intentions of adolescents who have yet to try tobacco smoking. The objective of this study was to examine the relationships between personality and affect-related risk factors measured by the Substance Use Risk Profile Scale (SURPS) and smoking intentions in a sample of adolescents who have not experimented with tobacco smoking. Data is based on responses from 1352 participants in the British Columbia Adolescent Substance Use Survey (56% female, 76% in Grade 8) who had never tried smoking tobacco. Of these 1352 participants, 29% (n=338) were classified as not having resolute intentions to not try smoking. Generalized estimating equations were used to examine the relationship between each SURPS dimension (Anxiety Sensitivity, Hopelessness, Impulsivity and Sensation Seeking) and the intention to try cigarettes in the future. Hopelessness (AOR 1.06, 95% CI [1.03, 1.10], p<.001), Impulsivity (AOR 1.07 [1.03, 1.11], p<.001) and Sensation Seeking (AOR 1.05 95% CI [1.02, 1.09], p<.01) had independent statistically significant associations with having an intention to try smoking. These findings may be used to inform a prevention-oriented framework to reduce susceptibility to tobacco smoking. PMID- 26803401 TI - Children's Environmental Health-The Role of Primordial Prevention. PMID- 26803400 TI - Reasons for electronic cigarette use beyond cigarette smoking cessation: A concept mapping approach. AB - INTRODUCTION: Electronic cigarettes (ECIGs) continue to grow in popularity, however, limited research has examined reasons for ECIG use. METHODS: This study used an integrated, mixed-method participatory research approach called concept mapping (CM) to characterize and describe adults' reasons for using ECIGs. A total of 108 adults completed a multi-module online CM study that consisted of brainstorming statements about their reasons for ECIG use, sorting each statement into conceptually similar categories, and then rating each statement based on whether it represented a reason why they have used an ECIG in the past month. RESULTS: Participants brainstormed a total of 125 unique statements related to their reasons for ECIG use. Multivariate analyses generated a map revealing 11, interrelated components or domains that characterized their reasons for use. Importantly, reasons related to Cessation Methods, Perceived Health Benefits, Private Regard, Convenience and Conscientiousness were rated significantly higher than other categories/types of reasons related to ECIG use (p<.05). There also were significant model differences in participants' endorsement of reasons based on their demography and ECIG behaviors. CONCLUSIONS: This study shows that ECIG users are motivated to use ECIGs for many reasons. ECIG regulations should address these reasons for ECIG use in addition to smoking cessation. PMID- 26803402 TI - Rapid and simultaneous determination of Strontium-89 and Strontium-90 in seawater. AB - A rapid method has been developed for the direct determination of radiostrontium ((89)Sr and (90)Sr) released in seawater in the early phase of an accident. The method employs a fast and effective pre-concentration of radiostrontium by Sr-Ca co-precipitation followed by separation of radiostrontium using extraction chromatography technique. Radiostrontium is effectively separated in the presence of excessive dominant salts of seawater. Cerenkov and liquid scintillation assay (LSA) techniques are used to determine (89)Sr and (90)Sr. Sample preparation time is approximately 4 h for a set of 10 samples. The method was validated using spiked seawater samples at various activity ratios of (89)Sr:(90)Sr ranging from 1:10 to 9:1. The mean chemical recovery of Sr was 85 +/- 3%. (90)Sr showed variable relative bias which enhanced with increasing ratio of (89)Sr:(90)Sr and was in the range +/- 21%. The highest biases of (90)Sr determination were due to lower activity concentrations of (90)Sr and are regarded as acceptable in emergency situations with elevated levels of radiostrontium in the sample. The minimum detectable concentration (MDC) of (90)Sr and (89)Sr varied at different (89)Sr:(90)Sr ratios. For 0.1 L seawater and 15 min counting time on a low background Hidex liquid scintillation counter (LSC), the MDC of (90)Sr was in the range of 1.7-3.5 Bq L(-1) and MDC of (89)Sr was in the range 0.5-2.4 Bq L(-1). PMID- 26803403 TI - A study on the levels of radioactivity in fish samples from the experimental lakes area in Ontario, Canada. AB - To better understand background radiation levels in country foods, a total of 125 fish samples were collected from three lakes (Lake 226, Lake 302 and Lake 305) in the Experimental Lakes Area (ELA) in Ontario of Canada during the summer of 2014. Concentrations of naturally occurring radionuclides ((226)Ra, (210)Pb and (210)Po) as well as anthropogenic radionuclides ((134)Cs and (137)Cs) were measured. This study confirmed that (210)Po is the dominant contributor to radiation doses resulting from fish consumption. While concentrations of (210)Pb and (226)Ra were below conventional detection limits, (210)Po was measured in almost all fish samples collected from the ELA. The average concentration was about 1.5 Bq/kg fresh weight (fw). None of the fish samples analysed in this study contained any detectable levels of (134)Cs. An average (137)Cs level of 6.1 Bq/kg fw was observed in freshwater fishes harvested in the ELA, almost twice that of samples measured in the National Capital Region of Canada in 2014 and more than 20 times higher than the levels observed in marine fish harvested from the Canadian west coast in 2013 and 2014. However, it is important to note that the concentrations of (137)Cs in fish samples from these inland lakes are considered very low from a radiological protection perspective. The resulting radiation dose for people from fish consumption would be a very small fraction of the annual dose from exposure to natural background radiation in Canada. The results indicate that fishes from inland lakes do not pose a radiological health concern. PMID- 26803404 TI - Intracellular replication of the well-armed pathogen Burkholderia pseudomallei. AB - The Burkholderia genus contains a group of soil-dwelling Gram-negative organisms that are prevalent in warm and humid climates. Two species in particular are able to cause disease in animals, B. mallei primarily infects Equus spp. and B. pseudomallei (BPS), that is able to cause potentially life-threatening disease in humans. BPS is naturally resistant to many antibiotics and there is no vaccine available. Although not a specialised human pathogen, BPS possesses a large genome and many virulence traits that allow it to adapt and survive very successfully in the human host. Key to this survival is the ability of BPS to replicate intracellularly. In this review we highlight recent advances in our understanding of the intracellular survival of BPS, including how it overcomes host immune defenses and other challenges to establish its niche and then spread the infection. Knowledge of these mechanisms increases our capacity for therapeutic interventions against a well-armed foe. PMID- 26803405 TI - Biofabrication of bone tissue: approaches, challenges and translation for bone regeneration. AB - The rising incidence of bone disorders has resulted in the need for more effective therapies to meet this demand, exacerbated by an increasing ageing population. Bone tissue engineering is seen as a means of developing alternatives to conventional bone grafts for repairing or reconstructing bone defects by combining biomaterials, cells and signalling factors. However, skeletal tissue engineering has not yet achieved full translation into clinical practice as a consequence of several challenges. The use of additive manufacturing techniques for bone biofabrication is seen as a potential solution, with its inherent capability for reproducibility, accuracy and customisation of scaffolds as well as cell and signalling factor delivery. This review highlights the current research in bone biofabrication, the necessary factors for successful bone biofabrication, in addition to the current limitations affecting biofabrication, some of which are a consequence of the limitations of the additive manufacturing technology itself. PMID- 26803406 TI - Kinetics and binding geometries of the complex between beta2-microglobulin and its antibody: An AFM and SPR study. AB - beta2-Microglobulin (B2M) is a human protein involved in the regulation of immune response and represents a useful biomarker for several diseases. Recently, anti B2M monoclonal antibodies have been introduced as innovative therapeutic agents. A deeper understanding of the molecular interaction between the two partners could be of utmost relevance for both designing array-based analytical devices and improving current immunotherapies. A visualization at the nanoscale performed by Atomic Force Microscopy revealed that binding of B2M to the antibody occurred according to two preferred interaction geometries. Additionally, Atomic Force Spectroscopy and Surface Plasmon Resonance provided us with detailed information on the binding kinetics and the energy landscape of the complex, both at the single molecule level and in bulk conditions. Combination of these complementary techniques contributed to highlight subtle differences in the kinetics behaviour characterizing the complexes. Collectively, the results may deserve significant interest for designing, development and optimization of novel generations of nanobiosensor platforms. PMID- 26803407 TI - Inhibition of tumor growth and metastasis by photoimmunotherapy targeting tumor associated macrophage in a sorafenib-resistant tumor model. AB - Tumor-associated macrophages (TAMs) play essential roles in tumor invasion and metastasis, and contribute to drug resistance. Clinical evidence suggests that TAM levels are correlated with local tumor relapse, distant metastasis, and poor prognosis in patients. In this study, we synthesized a TAM-targeted probe (IRD alphaCD206) by conjugating a monoclonal anti-CD206 antibody with a near-infrared phthalocyanine dye. We then investigated the potential application of the IRD alphaCD206 probe to near-infrared fluorescence (NIRF) imaging and photoimmunotherapy (PIT) of tumors resistant to treatment with the kinase inhibitor sorafenib. Sorafenib treatment had no effect on tumor growth in a 4T1 mouse model of breast cancer, but induced M2 macrophage polarization in tumors. M2 macrophage recruitment by sorafenib-treated 4T1 tumors was noninvasively visualized by in vivo NIRF imaging of IRD-alphaCD206. Small-animal single-photon emission computed tomography (SPECT)/CT and intratumoral microdistribution analysis indicated TAM-specific localization of the IRD-alphaCD206 probe in 4T1 tumors after several rounds of sorafenib treatment. Upon light irradiation, IRD alphaCD206 suppressed the growth of sorafenib-resistant tumors. In vivo CT imaging and ex vivo histological analysis confirmed the inhibition of lung metastasis in mice by IRD-alphaCD206 PIT. These results demonstrate the utility of the IRD-alphaCD206 probe for TAM-targeted diagnostic imaging and treatment of tumors that are resistant to conventional therapeutics. PMID- 26803408 TI - Black titania-based theranostic nanoplatform for single NIR laser induced dual modal imaging-guided PTT/PDT. AB - Substantially different from traditional combinatorial-treatment of photothermal therapy (PTT) and photodynamic therapy (PDT) by using multi-component nanocomposite under excitation of separate wavelength, a novel single near infrared (NIR) laser-induced multifunctional theranostic nanoplatform has been rationally and successfully constructed by a single component black titania (B TiO2-x) for effective imaging-guided cancer therapy for the first time. This multifunctional PEGylated B-TiO2-x shows high dispersity/stability in aqueous solution, excellent hemo/histocompatibility and broad absorption ranging from NIR to ultraviolet (UV). Both in vitro and in vivo results well demonstrated that such a novel multifunctional theranostic nanoplaform could achieve high therapeutic efficacy of simultaneous and synergistic PTT/PDT under the guidance of infrared thermal/photoacoustic (PA) dual-modal imaging, which was triggered by a single NIR laser. This research circumvents the conventional obstacles of using multi-component nanocomposites, UV light and high laser power density. Furthermore, negligible side effects to blood and main tissues could be found in 3 months' investigation, facilitating its potential biomedical application. PMID- 26803409 TI - Photoprotective efficiency of PLGA-curcumin nanoparticles versus curcumin through the involvement of ERK/AKT pathway under ambient UV-R exposure in HaCaT cell line. AB - Curcumin (Cur) has been demonstrated to have wide pharmacological window including anti-oxidant and anti-inflammatory properties. However, phototoxicity under sunlight exposure and poor biological availability limits its applicability. We have synthesized biodegradable and non-toxic polymer-poly (lactic-co-glycolic) acid (PLGA) encapsulated formulation of curcumin (PLGA-Cur NPs) of 150 nm size range. Photochemically free curcumin generates ROS, lipid peroxidation and induces significant UVA and UVB mediated impaired mitochondrial functions leading to apoptosis/necrosis and cell injury in two different origin cell lines viz., mouse fibroblasts-NIH-3T3 and human keratinocytes-HaCaT as compared to PLGA-Cur-NPs. Molecular docking studies suggested that intact curcumin from nanoparticles, bind with BAX in BIM SAHB site and attenuate it to undergo apoptosis while upregulating anti-apoptotic genes like BCL2. Real time studies and western blot analysis with specific phosphorylation inhibitor of ERK1 and AKT1/2/3 confirm the involvement of ERK/AKT signaling molecules to trigger the survival cascade in case of PLGA-Cur-NPs. Our finding demonstrates that low level sustained release of curcumin from PLGA-Cur-NPs could be a promising way to protect the adverse biological interactions of photo-degradation products of curcumin upon the exposure of UVA and UVB. Hence, the applicability of PLGA-Cur NPs could be suggested as prolonged radical scavenging ingredient in curcumin containing products. PMID- 26803411 TI - A robust super-tough biodegradable elastomer engineered by supramolecular ionic interactions. AB - Alginate-based supramolecular ionic polyurethanes (ASPUs) as mechanically tunable biomaterials with high strength and toughness in both dry and hydrated states are developed under metal-free conditions. The Young's modulus and tensile strength of ASPUs are tuned from 30 to 100 MPa, and 20 to 50 MPa, respectively. Interestingly, the ASPUs exhibit a small hysteresis loop, minimal loss of tensile strength and minimal creep deformation after 100 repetitive cycles which makes them of use for engineering of load-bearing tissues. This is the first report that describes a linear PU can resist a large number of cyclic stresses without significant stretching. These bio-based elastomers engineered by ionic interactions are biocompatible and biodegradable. The ASPUs demonstrate a similar in vivo degradation rate compared to polycaprolactone (PCL). These biomaterials also demonstrate a rapid self-healing and recovery after rupture, and have a linear biodegradation profile. Furthermore, histological examination of subcutaneous transplanted ASPUs after five months reveals low immunological response and low fibrosis. PMID- 26803410 TI - Fibrin matrices enhance the transplant and efficacy of cytotoxic stem cell therapy for post-surgical cancer. AB - Tumor-homing cytotoxic stem cell (SC) therapy is a promising new approach for treating the incurable brain cancer glioblastoma (GBM). However, problems of retaining cytotoxic SCs within the post-surgical GBM resection cavity are likely to significantly limit the clinical utility of this strategy. Here, we describe a new fibrin-based transplant approach capable of increasing cytotoxic SC retention and persistence within the resection cavity, yet remaining permissive to tumoritropic migration. This fibrin-based transplant can effectively treat both solid and post-surgical human GBM in mice. Using our murine model of image-guided model of GBM resection, we discovered that suspending human mesenchymal stem cells (hMSCS) in a fibrin matrix increased initial retention in the surgical resection cavity 2-fold and prolonged persistence in the cavity 3-fold compared to conventional delivery strategies. Time-lapse motion analysis revealed that cytotoxic hMSCs in the fibrin matrix remain tumoritropic, rapidly migrating from the fibrin matrix to co-localize with cultured human GBM cells. We encapsulated hMSCs releasing the cytotoxic agent TRAIL (hMSC-sTR) in fibrin, and found hMSC sTR/fibrin therapy reduced the viability of multiple 3-D human GBM spheroids and regressed established human GBM xenografts 3-fold in 11 days. Mimicking clinical therapy of surgically resected GBM, intra-cavity seeding of therapeutic hMSC-sTR encapsulated in fibrin reduced post-surgical GBM volumes 6-fold, increased time to recurrence 4-fold, and prolonged median survival from 15 to 36 days compared to control-treated animals. Fibrin-based SC therapy could represent a clinically compatible, viable treatment to suppress recurrence of post-surgical GBM and other lethal cancer types. PMID- 26803412 TI - A highly sensitive self assembled monolayer modified copper doped zinc oxide nanofiber interface for detection of Plasmodium falciparum histidine-rich protein 2: Targeted towards rapid, early diagnosis of malaria. AB - Rapid, ultrasensitive diagnostic/triaging kits for early detection of malarial parasites are critical for prevention of malarial epidemic, especially in developing and tropical countries. Unlike traditional microscopic diagnosis, these kits rely on the detection of antigens specific to malarial parasites. One such antigen which is routinely used in these diagnostic kits is Histidine-rich protein-2; a protein synthesized and released into the blood stream by the parasite Plasmodium falciparum. In this paper, we demonstrate an ultrasensitive nanobiosensor detection platform for Histidine-rich protein-2 having a limit of detection of attogram/ml. This nanobiosensor platform comprises of Mercaptopropylphosphonic acid functionalized copper doped zinc oxide nanofibers synthesized by electrospinning technique. Ultrasensitivity of attogram/ml can be attributed to the complimentary effects of Mercaptopropylphosphonic acid and copper doping in zinc oxide. Mercaptopropylphosphonic acid enhances the functional groups required for immobilizing antibody. Copper doping in zinc oxide not only increases the conductivity of the nanofibers but also pre-concentrates the target analyte onto the Mercaptopropylphosphonic acid treated nanofiber surface due to inherent electric field generated at the copper/zinc oxide heterojunction interface. The impedimetric detection response of copper-doped zinc oxide nanofiber modified electrode shows excellent sensitivity (28.5 kOmega/(gm/ml)/cm(2)) in the detection ranges of 10 ag/ml-10 ug/ml, and a detection limit of 6 attogram/ml. In addition, the proposed biosensor is highly selective to targeted HRP2 protein with a relative standard deviation of 1.9% in the presence of various interference of nonspecific molecules. To the best of our knowledge, this biosensor shows the lowest detection limit of malarial parasites reported in the literature spanning different nanomaterials and different detection mechanisms. Since the nanobiosensor platform is based on immunoassay technique, with a little modification, it can be extended for developing point-of care diagnostic devices for several biomarkers of importance. PMID- 26803413 TI - Porous silicon membrane-modified electrodes for label-free voltammetric detection of MS2 bacteriophage. AB - A proof of concept for the label-free detection of bacteriophage MS2, a model indicator of microbiological contamination, is validated in this work as a porous silicon (pSi) membrane-based electrochemical biosensor. PSi membranes were used to afford nanochannel architectures. The sensing mechanism was based on the nanochannel blockage caused by MS2 binding to immobilized capture antibodies. This blockage was quantified by measuring the oxidation current of the electroactive species reaching the electrode surface, by means of differential pulse voltammetry (DPV). The immunosensor showed a limit of detection of 6 pfu/mL in buffer, allowing the detection of MS2 to levels commonly found in real-world applications, and proved to be unaffected by matrix effects when analyzing MS2 in reservoir water. This platform enables the straightforward, direct and sensitive detection of a broad range of target analytes and constitutes a promising approach towards the development of portable electronic point of sample analysis devices. PMID- 26803414 TI - The isothermal amplification detection of double-stranded DNA based on a double stranded fluorescence probe. AB - Here we have developed a novel method of isothermal amplification detection of double-stranded DNA (dsDNA) based on double-stranded fluorescence probe (ds probe). Target dsDNA repeatedly generated single-stranded DNA (ssDNA) with polymerase and nicking enzyme. The ds-probe as a primer hybridized with ssDNA and extended to its 5'-end. The displaced ssDNA served as a new detection target to initiate above-described reaction. Meanwhile, the extended ds-probe could dynamically dissociate from ssDNA and self-hybridize, converting into a turn-back structure to initiate another amplification reaction. In particular, the ds-probe played a key role in the entire experimental process, which not only was as a primer but also produced the fluorescent signal by an extension and displacement reaction. Our method could detect the pBluescript II KS(+) plasmid with a detection limit of 2.3 amol, and it was also verified to exhibit a high specificity, even one-base mismatch. Overall, it was a true isothermal dsDNA detection strategy with a strongly anti-jamming capacity and one-pot, only requiring one ds-probe, which greatly reduced the cost and the probability of contamination. With its advantages, the approach of dsDNA detection will offer a promising tool in the field of point-of-care testing (POCT). PMID- 26803415 TI - Quantitative analysis of peak torque and power-velocity characteristics of shoulder rotator muscles after arthroscopic labral repair. AB - OBJECTIVES: We aimed to use biomechanical testing to assess differences in the power and strength of patients who participated in a short-term, home-based rehabilitation program following arthroscopic labral repair compared with a healthy control group. DESIGN: The functional outcomes of patients who underwent arthroscopic labral repair followed by self-directed short-term rehabilitation at home were compared with age- and body mass index (BMI)-matched healthy controls. METHODS: Group I included 20 male patients who had undergone arthroscopic labral repair after being diagnosed with recurrent anterior glenohumeral joint instability without bony lesions of the humeral head or glenoid. Postoperatively, they participated in physical therapy for 17+/-4 appointments, followed by self guided home-based exercises. Group II included 25 males without injuries. The two groups were matched for age and BMI. The orthopaedic examination, functional tests, and biomechanical measurements were performed under isokinetic conditions at an average of 16+/-3 months postoperatively. RESULTS: Significant differences were observed in range of shoulder rotation on the operative shoulder compared with the unaffected side and in the dominant arms of the control group. The patients were also found to have significant deficits in biomechanical parameters such as power and peak torque angle. CONCLUSIONS: Significant deficits in peak torque, power, and peak torque angle during external and internal shoulder rotation remained up to 16 months after arthroscopic labral repair. Further research is needed to understand the changes in shoulder power assessment after labral repair. PMID- 26803416 TI - Simultaneous quantitation of polymyxin B1, polymyxin B2 and polymyxin B1-1 in human plasma and treated human urine using solid phase extraction and liquid chromatography-tandem mass spectrometry. AB - Two liquid chromatographic-tandem mass spectrometric (LC-MS/MS) methods have been developed and validated for the quantitative determination of polymyxin B1, polymyxin B2 and polymyxin B1-1 concentrations in human plasma and treated urine. During method development, technical challenges such as the separation of structural isomers polymyxin B1and polymyxin B1-1 and nonspecific binding in urine samples were encountered and overcome. Two automated solid phase extraction methods were used to extract plasma samples (100MUL) and urine samples (200MUL) and the resulting extracts were analyzed using reversed phase LC-MS/MS with an electrospray (ESI) interface and selected reaction monitoring (SRM) in the positive ionization mode. Both methods were validated over a calibration curve range of 5.00-2000ng/mL with a linear regression and 1/x(2) weighting. The between-run relative standard deviation (%RSD) ranged from 4.5 to 9.5% for the plasma assay and from 1.1 to 7.1% for the urine assay. For the plasma assay, the between-run accuracy ranged from 100.5 to 115.2% of nominal at all QC concentrations including the LLOQ. For the urine assay, the between-run accuracy ranged from 92.0 to 106% of nominal at all QC concentrations including the LLOQ. The extraction recoveries for all polymyxins in both assays were between 54.0 and 64.2%. Long term matrix storage stability for all polymyxins was established at both -20 degrees C and -70 degrees C for up to 85 days in human plasma and for up to 55 days in treated human urine. Both assays were used for the measurement of polymyxin B1, polymyxin B2 and polymyxin B1-1 concentrations in human plasma and treated urine for the determination of bioequivalence and toxicokinetic parameters in clinical studies. PMID- 26803417 TI - Differences in object sharing between infants at risk for autism and typically developing infants from 9 to 15 months of age. AB - Object sharing abilities of infants at risk for autism (AR infants) and typically developing (TD) infants were compared from 9 to 15 months of age. Specifically, we examined the effects of infants' locomotor abilities on their object sharing skills. 16 TD infants and 16 AR infants were observed during an "object sharing" paradigm at crawling and walking ages. Overall, AR walking infants demonstrated lower rates of object sharing with caregivers compared to TD walking infants. Specifically, AR walking infants had lower rates of giving and approaches toward caregivers compared to TD walking infants. AR walking infants also had lower step rates toward task-appropriate targets, i.e. caregivers and objects compared to TD walking infants. No group differences in object sharing were observed at crawling ages. Object sharing could be a valuable context for early identification of delays in infants at risk for developing Autism spectrum disorder. PMID- 26803418 TI - Temporal Trends and Outcomes of Patients Undergoing Percutaneous Coronary Interventions for Cardiogenic Shock in the Setting of Acute Myocardial Infarction: A Report From the CathPCI Registry. AB - OBJECTIVES: The purpose of this study was to examine the temporal trends in demographics, clinical characteristics, management strategies, and in-hospital outcomes in patients with acute myocardial infarction complicated by cardiogenic shock (CS-AMI) who underwent percutaneous coronary intervention (PCI) from the Cath-PCI Registry (2005 to 2013). BACKGROUND: The authors examined contemporary use and outcomes of PCI in patients with CS-AMI. METHODS: The authors used the Cath-PCI Registry to evaluate 56,497 patients (January 2005 to December 2013) undergoing PCI for CS-AMI. Temporal trends in clinical variables and outcomes were assessed. RESULTS: Compared with cases performed from 2005 to 2006, CS-AMI patients receiving PCI from 2011 to 2013 were more likely to have diabetes, hypertension, dyslipidemia, previous PCI, dialysis, but less likely to have chronic lung disease, peripheral vascular disease, or heart failure within 2 weeks (p < 0.01). Between 2005 and 2006 to 2011 and 2013, intra-aortic balloon pump use decreased (49.5% to 44.9%; p < 0.01), drug-eluting stent use declined (65% to 46%; p < 0.01), and the use of bivalirudin increased (12.6% to 45.6%). Adjusted in-hospital mortality; increased (27.6% in 2005 to 2006 vs. 30.6% in 2011 to 2013, adjusted odds ratio: 1.09, 95% confidence interval: 1.005 to .173; p = 0.04) for patients who were managed with an early invasive strategy (<24 h from symptoms). CONCLUSIONS: Our study shows that despite the evolution of medical technology and use of contemporary therapeutic measures, in-hospital mortality in CS-AMI patients who are managed invasively continues to rise. Additional research and targeted efforts are indicated to improve outcomes in this high-risk cohort. PMID- 26803419 TI - What Happens in the Cath Lab Stays in the Cath Lab, or Does It?: Intraprocedural Thrombotic Events in Patients With Acute Coronary Syndromes. PMID- 26803420 TI - Trends in Complications and Outcomes of Patients Undergoing Transfemoral Transcatheter Aortic Valve Replacement: Experience From the PARTNER Continued Access Registry. AB - OBJECTIVES: The aim of this study was to examine trends in the rates of complications and outcomes of patients undergoing transfemoral transcatheter aortic valve replacement (TF-TAVR). BACKGROUND: It is unknown whether an evolution of case selection or accrual of case experience over time has resulted in a change in the rates of complications and outcomes of patients undergoing TF TAVR. METHODS: TF-TAVR patients enrolled in the PARTNER (Placement of AoRTic TraNscathetER Valve Trial) nonrandomized continued access registry (N = 1,063, enrolled March 2011 to January 2012 after completion of the randomized trial) were divided into tertiles (T1 through T3) based on enrollment date. Patient characteristics and rates of adverse events were compared over time. RESULTS: There were no significant differences in sex, New York Heart Association functional classes III/IV, diabetes, coronary artery disease, previous revascularization, pulmonary hypertension, renal disease, or liver disease. There was an increase in mean age, but a decrease in porcelain aorta, chronic obstructive pulmonary disease (including oxygen-dependent chronic obstructive pulmonary disease), previous chest wall radiation, and a slight decrease in the median Society of Thoracic Surgeons Predicted Risk of Mortality score. There was a significant decline in the frequency of patients deemed "inoperable" (cohort B) and in need for post-dilation. Percutaneous access increased significantly. There were no differences in post-procedural stroke, major bleeding, major vascular complications, or the need for aortic valve reintervention over time. The incidence of moderate/severe paravalvular regurgitation declined significantly as did all-cause mortality at 1 and 2 years. CONCLUSIONS: A significant reduction in the incidence of moderate/severe paravalvular regurgitation as well as longer term all-cause mortality was observed over time. The cause of these reductions was likely multifactorial, including improved case selection and procedural techniques and increased site experience. (THE PARTNER TRIAL [Placement of AoRTic TraNscathetER Valve Trial]; NCT00530894). PMID- 26803421 TI - Transcatheter Aortic Valve Replacement: A Revolution in Evolution. PMID- 26803422 TI - Which Intraprocedural Thrombotic Events Impact Clinical Outcomes After Percutaneous Coronary Intervention in Acute Coronary Syndromes?: A Pooled Analysis of the HORIZONS-AMI and ACUITY Trials. AB - OBJECTIVES: This study sought to determine the extent to which individual components of intraprocedural thrombotic events (IPTEs) are associated with adverse events. BACKGROUND: IPTEs occurring during percutaneous coronary intervention (PCI) are associated with adverse in-hospital and late outcomes in patients with acute coronary syndromes. METHODS: A total of 6,591 patients who underwent PCI for non-ST-segment elevation acute coronary syndromes/ST-segment elevation myocardial infarction in the ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) and HORIZONS-AMI (Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction) trials underwent detailed frame-by-frame core laboratory angiographic analysis to assess for IPTEs. The associations of IPTE components with death, major bleeding, and major adverse cardiac events at 30 days were assessed using univariable analyses and multivariable models. RESULTS: The overall incidence of IPTEs was 7.7%, with a greater incidence in ST-segment elevation myocardial infarction patients (12.2%) compared with non-ST-segment elevation acute coronary syndromes patients (3.5%). Specific components of IPTEs included no-reflow/slow reflow in 58.0%, new/worsened thrombus in 35.3%, distal embolization in 34.9%, abrupt closure in 19.8%, and intraprocedural stent thrombosis (IPST) in 9.5% of patients. Each IPTE component was independently associated with 30-day death, major bleeding, and MACE in multivariable models, with the strongest association observed for IPST (MACE hazard ratio: 7.51 [95% confidence interval: 4.36 to 12.94]). CONCLUSIONS: The occurrence of IPTEs is not infrequent among high-risk acute coronary syndromes patients undergoing PCI, and each IPTE component was associated with subsequent adverse events. Although IPST represented <10% of IPTE events overall, it was the component with the strongest association with adverse events. PMID- 26803423 TI - Bioresorbable Scaffold Failure Due to Chronic Recoil in a Myocardial Bridge. PMID- 26803424 TI - Left Anterior Descending Coronary Artery Obstruction Associated With an Apical Suture After Transcatheter Aortic Valve Replacement. PMID- 26803425 TI - Endovascular Reperfusion Strategies for Acute Stroke. AB - Stroke is the most common cause of permanent disability, the second most common cause of dementia, and the third most common cause of death in the Western world. About 10% to 20% of strokes are due to large-artery occlusions causing severe disabling strokes. Recently, 5 randomized controlled trials established mechanical thrombectomy in stroke treatment in patients with large-vessel occlusions. The current intra-arterial reperfusion therapies allow high recanalization rates, high rates of favorable clinical outcome, and low complication rates. This review discusses the results of recent randomized trials and describes the current state-of-the-art endovascular treatment in acute ischemic stroke. PMID- 26803426 TI - Endovascular Repair for Pulmonary Artery and Aortic Dissection Associated With Patent Ductus Arteriosus. PMID- 26803427 TI - Disappointing Results, But We Must Carry On. PMID- 26803428 TI - Number of patient-reported allergies helps distinguish epilepsy from psychogenic nonepileptic seizures. AB - Psychogenic nonepileptic seizures (PNES) are relatively common, accounting for 5 40% of visits to tertiary epilepsy centers. Inpatient video-electroencephalogram (vEEG) monitoring is the gold standard for diagnosis, but additional positive predictive tools are necessary given vEEG's relatively scarce availability. In this study, we investigated if the number of patient-reported allergies distinguishes between PNES and epilepsy. Excessive allergy-reporting, like PNES, may reflect somatization. Using electronic medical records, ICD-9 codes, and text identification algorithms to search EEG reports, we identified 905 cases of confirmed PNES and 5187 controls with epilepsy but no PNES. Patients with PNES averaged more self-reported allergies than patients with epilepsy alone (1.93 vs. 1.00, p<0.001). Compared to those with no allergies, each additional allergy linearly increased the percentage of patients with PNES by 2.98% (R(2)=0.71) such that with >=12 allergies, 12/28 patients (42.8%) had PNES compared to 349/3368 (11.6%) of the population with no allergies (odds ratio=6.49). This relationship remained unchanged with logistic regression analysis. We conclude that long allergy lists may help identify patients with PNES. We hypothesize that a tendency to inaccurately self-report allergies reflects a maladaptive externalization of psychologic distress and that a similar mechanism may be responsible for PNES in some patients with somatic symptom disorder. PMID- 26803429 TI - Progression of carotid vascular damage and cardiovascular events in non-alcoholic fatty liver disease patients compared to the general population during 10 years of follow-up. AB - BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is associated not only with liver related morbidity and mortality but also with an increased risk of cardiovascular disease. AIM: to evaluate in patients with NAFLD and in matched Controls after 10 years of follow-up 1 the incidence of major cardiovascular and cerebral events 2 the progression of vascular damage. METHODS: Clinical and cardio-metabolic data were collected in 125 NAFLD patients and 250 age and gender matched Controls at baseline and 10 years later. Incidence of cardiovascular and cerebral events was recorded. By ultrasonography, carotid intima-media thickness (cIMT), presence of plaques and presence of fatty liver were evaluated. RESULTS: 25% of the overall series was lost to follow-up. Sixty-eight (37%) Controls developed steatosis. Major cardiovascular events were observed in thirty-five subjects (17/91 (19%) NAFLD and 18/182 (10%) Controls), with an estimated cumulative risk significantly higher in NAFLD than in Controls, log-rank test for equality of failure functions p = 0.007. At multivariate analysis, presence of plaques (hazard ratio 5.08 (95% C.I. 2.56-10.96) and of steatosis (hazard ratio 1.99 (1.01-3.94)) were the strongest predictors for cardiovascular events. Grade of steatosis, ALT and GGT levels were higher in NAFLD patients who developed cardiovascular events. cIMT value after 10 years was significantly higher in NAFLD than in Controls, but the mean progression rate was higher in Controls (0.015 and 0.006 mm/year, p = 0.001). In conclusion our results suggest that NAFLD has to be included among risk factors for cardiovascular damage and underline the utility to evaluate, once NAFLD is diagnosed, the presence of atherosclerotic lesions. PMID- 26803430 TI - Lipoprotein (a) is related to coronary atherosclerotic burden and a vulnerable plaque phenotype in angiographically obstructive coronary artery disease. AB - BACKGROUND: Lipoprotein Lp(a) has been shown to be an independent risk factor for coronary artery disease (CAD). However, its association with CAD burden in patients with ACS is largely unknown, as well as the association of Lp(a) with lipid rich plaques prone to rupture. AIM: We aim at assessing CAD burden by coronary angiography and plaque features including thin cap fibroatheroma (TCFA) by optical coherence tomography (OCT) in consecutive patients presenting with acute coronary syndrome (ACS) and obstructive CAD along with serum Lp(a) levels. METHODS: This study comprises an angiographic and an OCT cohort. A total of 500 ACS patients (370 men, average age 66 +/- 11) were enrolled for the angiographic cohort and 51 ACS patients (29 males, average age 65 +/- 11) were enrolled for the OCT cohort. Angiographic CAD severity was assessed by Sullivan score and by Bogaty score including stenosis score and extent index. OCT plaque features were evaluated at the site of the minimal lumen area and along the culprit segment. RESULTS: In the angiographic cohort, at multivariate analysis, Lp(a) was a weak independent predictor of Sullivan score (p < 0.0001), stenosis score (p < 0.0001) and extent index (p < 0.0001). In the OCT cohort, patients with higher Lp(a) levels (>= 30 md/dl) compared to patients with lower Lp(a) levels (<30 md/dl) exhibited a higher prevalence of lipidic plaque at the site of the culprit stenosis (67% vs. 27%; P = 0.02), a wider lipid arc (135 +/- 114 vs 59 +/- 111; P = 0.03) and a higher prevalence of TCFA (38% vs. 10%; P = 0.04). CONCLUSIONS: Among patients with ACS, raised Lp(a) levels are associated with an increased atherosclerotic burden and it identifies a subset of patients with features of high risk coronary atherosclerosis. PMID- 26803431 TI - Weight loss is superior to exercise in improving the atherogenic lipid profile in a sedentary, overweight population with stable coronary artery disease: A randomized trial. AB - BACKGROUND: Dyslipidemia and low-grade inflammation are integral in the pathogenesis of atherosclerosis. We aim to compare the effects of a considerable weight loss and intensive exercise training on lipid atherogenicity and low-grade inflammation in a high-risk population with coronary artery disease (CAD). METHODS: Seventy non-diabetic participants with CAD, BMI 28-40 kg/m(2), age 45-75 years were randomized to 12 weeks' aerobic interval training (AIT) at 85-90% of peak heart rate three times/week or a low energy diet (LED, 800-1000 kcal/day) for 8-10 weeks followed by 2-4 weeks' weight maintenance diet. Lipid profile atherogenicity was described using lipoprotein particle size and density profiling. Low-grade inflammation was evaluated by tumor necrosis factor alpha (TNFalpha), C-reactive protein, interleukin 6 and soluble urokinase plasminogen activator receptor. RESULTS: Twenty-six (74%) AIT and 29 (83%) LED participants completed intervention per protocol. AIT and LED decreased total (AIT: -518 { 906;-129},P = 0.011, LED: -767 {-1128:-406},P < 0.001) and low-density lipoprotein (LDL, AIT: -186 {-306;-65},P = 0.004, LED: -277 {-433;-122},P < 0.001) assessed as the area under the density profile curve. LED was superior to AIT in decreasing atherogenicity reflected by increased LDL (between-group: 1.0 A {0.4; 1.7},P = 0.003) and high-density lipoprotein (between-group: 1.2 A {0.2; 2.4},P = 0.026) particle size and a decreased proportion of total lipoprotein constituted by the small, dense LDL5 subfraction (between-group: -5.0% {-8.4; 1.7},P = 0.004). LED decreased TNFalpha (9.5% {-15.8;-2.6},P = 0.009). No changes were seen following AIT. CONCLUSION: LED and AIT decreased total and LDL lipoprotein. LED was superior in decreasing atherogenicity assessed by a shift in density profile and increased particle size. Effect on low-grade inflammation was limited. PMID- 26803433 TI - Effect of hypertension on preoperative neutrophil-lymphocyte ratio evaluation of prognosis of renal cell carcinoma. AB - OBJECTIVES: As an indicator of inflammatory reaction of immune system, the neutrophil-lymphocyte ratio (NLR) is a significantly independent prognostic factor of renal cell carcinoma (RCC). However, the NLR was not added in any well established prognostic models. Many physiologic factors were also associated with NLR, such as hypertension. As such, we evaluated the effect of hypertension on NLR evaluation of prognosis of RCC. MATERIALS AND METHODS: Hematological parameters and clinicopathological data during diagnosis were retrospectively recorded for 401 patients with RCC between the years 1999 and 2009. The standardized cutoff-finder algorithm was used to find the suitable NLR cutoff value for recurrence. The Log-rank test and Kaplan-Meier method were used to compare and estimate the recurrence-free survival. Univariate and multivariate Cox regression analyses were used to evaluate the association between NLR and clinicopathologic outcomes. RESULTS: In the analysis of total subjects, recurrence-free survival was significantly worse among patients with a preoperative NLR (>3.139 [21.9%] vs.<=3.139 [78.1%]; P<0.001). High NLR value was associated with high pathological TNM stage (P = 0.009, 0.018, 0.001, respectively). In the normotensive subgroup, recurrence-free survival was also significantly worse among patients with a preoperative NLR (>3.139 [22.6%] vs.<=3.139 [77.4%]; P<0.001). However, in the subgroup with hypertension, the difference of recurrence-free survival was not significant between patients with preoperative NLR (>3.139 [21.2%] vs.<=3.139 [78.8%]; P = 0.093). Moreover, multivariate analysis identified increased NLR as a poor prognosis index for recurrence-free survival in total group (hazard ratio [HR] = 2.27; 95% CI: 1.50 3.44; P<0.001) and normotensive subgroup (HR = 2.97; 95% CI: 1.74-5.07; P<0.001), but not in hypertensive subgroup (HR = 1.25; 95% CI: 0.59-2.65; P = 0.566). CONCLUSIONS: Hypertension is a disturbance factor in the evaluation of prognosis of RCC by preoperative NLR. PMID- 26803432 TI - High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort. AB - BACKGROUND AND AIMS: Recent failures of HDL cholesterol (HDL-C)-raising therapies to prevent cardiovascular disease (CVD) events have tempered the interest in the role of HDL-C in clinical risk assessment. Emerging data suggest that the atheroprotective properties of HDL depend on specific HDL particle characteristics not reflected by HDL-C. The purpose of this study was to determine the association of HDL particle concentration (HDL-P) and HDL subclasses with mortality in a high-risk cardiovascular population and to examine the clinical utility of these parameters in mortality risk discrimination and reclassification models. METHODS: Using nuclear magnetic resonance spectroscopy, we measured HDL-P and HDL subclasses in 3972 individuals enrolled in the CATHGEN coronary catheterization biorepository; tested for association with all-cause mortality in robust clinical models; and examined the utility of HDL subclasses in incremental mortality risk discrimination and reclassification. RESULTS: Over an average follow-up of eight years, 29.6% of the individuals died. In a multivariable model adjusted for ten CVD risk factors, HDL-P [HR, 0.71 (0.67 0.76), p = 1.3e-24] had a stronger inverse association with mortality than did HDL-C [HR 0.93 (0.87-0.99), p = 0.02]. Larger HDL size conferred greater risk and the sum of medium- and small-size HDL particles (MS-HDL-P) conferred less risk. Furthermore, the strong inverse relation of HDL-P levels with mortality was accounted for entirely by MS-HDL-P; HDL-C was not associated with mortality after adjustment for MS-HDL-P. Addition of MS-HDL-P to the GRACE Risk Score significantly improved risk discrimination and risk reclassification. CONCLUSION: HDL-P and smaller HDL subclasses were independent markers of residual mortality risk and incremental to HDL-C in a high-risk CVD population. These measures should be considered in risk stratification and future development of HDL targeted therapies in high-risk populations. PMID- 26803434 TI - Trends in the utilization of imaging for upper tract urothelial carcinoma. AB - OBJECTIVES: To evaluate the changes in use of the different imaging modalities for diagnosing upper tract urothelial carcinoma (UTUC) and assess how these changes have affected tumor stage at the time of surgery. MATERIALS AND METHODS: We assessed the Surveillance, Epidemiology, and End Results (SEER) cancer registry and linked Medicare claims data (1992-2009) for 5377 patients who underwent surgery for UTUC. We utilized International Classification of Disease Oncology 3 codes to identify UTUC. International Classification of Disease, ninth Revision, Clinical Modification and Current Procedure Terminology codes identified surgical treatment and imaging modalities. We assessed for use of intravenous pyelography, retrograde pyelography (RGP), computed tomography urography (CTU), magnetic resonance urography (MRU), and endoscopy. For each modality, patients were categorized as having received the modality at least once or not at all. Patient characteristics were compared using chi-squared tests. Usage of imaging modalities and tumor stage was trended using Cochran-Armitage tests. We stratified our data into 2 multivariate logistic regression models to determine the effect of imaging modalities on tumor stage: 1992 to 1999 with all modalities except MRU, and 2000 to 2009 with all modalities. RESULTS: Our patient population was predominantly White males of more than 70 years old. Intravenous pyelography and RGP declined in use (62% and 72% in 1992 vs. 6% and 58% in 2009, respectively) while computed tomography urography, MRU, and endoscopy increased in use (2%, 0%, and 37% in 1992 vs. 44%, 6%, and 66% in 2009, respectively). In both regression analyses, endoscopy was associated with lower-stage tumors. In the 2000 to 2009 model, RGP was associated with lower-stage tumors, and MRU was associated with higher-stage tumors. Finally, our data showed an increasing number of modalities utilized for each patient (1% receiving 4 modalities in 1992 vs. 20% in 2009). CONCLUSIONS: We found trends toward the utilization of newer imaging modalities to diagnose UTUC and more modalities per patient. Endoscopy and RGP were associated with smaller tumors, whereas MRU was associated with larger tumors. Further studies are needed to evaluate the utility of the different modalities in diagnosing UTUC. PMID- 26803435 TI - Body mass index and age are additional prognostic factors in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors. AB - PURPOSE: Tyrosine kinase inhibitors (TKIs) are the preferred treatment drugs for metastatic renal cell carcinoma (mRCC). The aim of this study was to analyze prognostic factors for overall survival (OS) in patients with mRCC treated with TKIs. MATERIALS AND METHODS: Clinical data on 155 patients enrolled in 5 clinical trials conducted at our hospital from 2006 to 2014 were reviewed retrospectively. All patients received first-line TKI therapy (sunitinib, sorafenib, pazopanib, or famitinib). Survival rates were determined by the Kaplan-Meier method. RESULTS: Median OS (mOS) was 36.2 months. A total of 4 of the 5 adverse prognostic factors identified by the Memorial Sloan-Kettering Cancer Center (MSKCC) were found to be independent predictors of shorter survival, anemia, hypercalcemia, lactate dehydrogenase>1.5*upper limit of normal, and diagnosis to treatment time<1 year. In addition, we found that age<=45 years (P = 0.002), low or high body mass index ([BMI]<19 or>30kg/m(2)) (P = 0.003), and presence of>=3 metastatic sites (P = 0.000) were also independent adverse prognostic factors. According to the MSKCC model, the mOS time in the favorable-risk, intermediate-risk, and poor-risk groups were 46.6, 30.4 and 16.7 months, respectively (P = 0.005). When we integrated age and BMI into the MSKCC model to set up a 7-factor prognostic model, we found the mOS time for these 3 groups was 71.1, 41.6 and 15.3 months, respectively (P = 0.000). CONCLUSION: Age and BMI are additional independent prognostic factors for patients with mRCC receiving vascular endothelial growth factor receptor-targeted TKI treatment, and the MSKCC prognostic model is also applicable to them. A 7-factor prognostic model might help to identify patients with the best prognosis. Further studies are needed to confirm these findings. PMID- 26803436 TI - General practice trainees face practice ownership with fear. AB - Objectives The aim of the present secondary analysis of data collected in a grounded theory study was to explore the perceptions of Registrars and new Fellows to practice ownership and management. Methods Focus groups and interviews with Registrars and recent Fellows were undertaken to explore the desire to become an owner, facilitators and barriers to practice ownership and delivery models for practice ownership education. A secondary thematic analysis was conducted to understand emerging concepts related to perceptions of general practice ownership. Results A surprisingly strong theme of fear was evident across focus group and interview participants. Expressed fear was specifically related to financial concerns, lack of relevant knowledge and skills and concern over balancing different roles. Moderating factors included previous life and educational experiences, as well as role modelling. Conclusions Graduation of a cohort of new general practitioners (GPs) who express fear towards practice ownership is concerning. Creating more positive learning environments and opportunity for open discussion regarding practice management and ownership is an important step in providing adequate support for new GPs to give serious consideration to career options. What is known about the topic? The traditional model of general practice ownership has been for a doctor to own and/or manage the practice. Fewer new GPs are taking on the role of owning a general practice, and disinterest has been presumed to play a significant role in this trend. It has been reported that current curricula provide insufficient focus on providing learning opportunities for general practice trainees on ownership and management models; however, recent research has shown that general practice trainees have a strong interest in receiving this knowledge during their training. What does this paper add? The present qualitative research evaluated the emotional response that general practice trainees (Registrars) expressed when they considered practice ownership. GP Registrars expressed fear when asked about the prospect of owning their own practice. This may be influenced by the role modelling they receive during their training. What are the implications for practitioners? Supervisors involved in general practice training should ensure their trainees have the opportunity to learn about practice ownership during their training. Supervisors should also be aware that their own behaviour and attitudes towards practice ownership is observed by their trainees and it can colour the emotional response the trainee has when considering owning a practice. PMID- 26803437 TI - Re: Salibi A, Morritt AN. Easy access to the calf for the lone surgeon. PMID- 26803438 TI - Isolated bony syngnathia. PMID- 26803439 TI - Theory of chromatography of partially cyclic polymers: Tadpole-type and manacle type macromolecules. AB - A theory of chromatography is developed for partially cyclic polymers of tadpole- and manacle-shaped topological structures. We present exact equations for the distribution coefficient K at different adsorption interactions; simpler approximate formulae are also derived, relevant to the conditions of size exclusion, adsorption, and critical chromatography. Theoretical chromatograms of heterogeneous partially cyclic polymers are simulated, and conditions for good separation by topology are predicted. According to the theory, an effective SEC radius of tadpoles and manacles is mostly determined by the molar mass M, and by the linear-cyclic composition. In the interactive chromatography, the effect of molecular topology on the retention becomes significant. At the critical interaction point, partial dependences K(Mlin) and K(Mring) are qualitatively different: while being almost independent of Mlin, K increases with Mring. This behavior could be realized in critical chromatography-for separation of partially cyclic polymers by the number and molar mass of cyclic elements. PMID- 26803441 TI - Sharing clinical trial data: a proposal from the International Committee of Medical Journal Editors. PMID- 26803440 TI - Preparation of alumina nanoshell coated porous silica spheres for inorganic anions separation. AB - It had been reported that alumina nanoshell coating could be obtained on the external surface of various substrates in one-nanometer precision in aqueous solution. In this work, alumina nanoshell coated mesoporous silica microbeads (nanoAl2O3/mesoSiO2) were prepared with the similar method, and were successfully applied to inorganic anions separation. As the mass transfer speed is largely constrained in the mesopore compared with that on the open surface, it was found that a complete alumina nanoshell coating could be obtained within the mesopore until the five-time coating was carried out. After characterization by BET, SEM and FTIR, it was found that the obtained nanoAl2O3/mesoSiO2 particles are smooth and well dispersed, and the mesopores are well reserved. In addition, the full coverage of nanoAl2O3 shell in mesopores was also confirmed by the binding capacity experiments with berberine. Finally, the nanoAl2O3/mesoSiO2 particles were packed in silica capillary for the separation of inorganic anions I(-), SCN( ), Br(-), NO2(-) and NO3(-) with ion chromatography (IC), and a column efficiency of 3.8 * 10(4) plates per meter was obtained for I(-). PMID- 26803442 TI - Time to take tobacco dependence treatment seriously. PMID- 26803443 TI - Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial. AB - BACKGROUND: Sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA2a) activity is deficient in the failing heart. Correction of this abnormality by gene transfer might improve cardiac function. We aimed to investigate the clinical benefits and safety of gene therapy through infusion of adeno-associated virus 1 (AAV1)/SERCA2a in patients with heart failure and reduced ejection fraction. METHODS: We did this randomised, multinational, double-blind, placebo-controlled, phase 2b trial at 67 clinical centres and hospitals in the USA, Europe, and Israel. High-risk ambulatory patients with New York Heart Association class II-IV symptoms of heart failure and a left ventricular ejection fraction of 0.35 or less due to an ischaemic or non-ischaemic cause were randomly assigned (1:1), via an interactive voice and web-response system, to receive a single intracoronary infusion of 1 * 10(13) DNase-resistant particles of AAV1/SERCA2a or placebo. Randomisation was stratified by country and by 6 min walk test distance. All patients, physicians, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was time to recurrent events, defined as hospital admission because of heart failure or ambulatory treatment for worsening heart failure. Primary efficacy endpoint analyses and safety analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01643330. FINDINGS: Between July 9, 2012, and Feb 5, 2014, we randomly assigned 250 patients to receive either AAV1/SERCA2a (n=123) or placebo (n=127); 243 (97%) patients comprised the modified intention-to-treat population. Patients were followed up for at least 12 months; median follow-up was 17.5 months (range 1.8-29.4 months). AAV1/SERCA2a did not improve time to recurrent events compared with placebo (104 vs 128 events; hazard ratio 0.93, 95% CI 0.53-1.65; p=0.81). No safety signals were noted. 20 (16%) patients died in the placebo group and 25 (21%) patients died in the AAV1/SERCA2a group; 18 and 22 deaths, respectively, were adjudicated as being due to cardiovascular causes. INTERPRETATION: CUPID 2 is the largest gene transfer study done in patients with heart failure so far. Despite promising results from previous studies, AAV1/SERCA2a at the dose tested did not improve the clinical course of patients with heart failure and reduced ejection fraction. Although we did not find evidence of improved outcomes at the dose of AAV1/SERCA2a studied, our findings should stimulate further research into the use of gene therapy to treat patients with heart failure and help inform the design of future gene therapy trials. FUNDING: Celladon Corporation. PMID- 26803444 TI - Analytical approaches for clarification of DNA-double decker phthalocyanine binding mechanism: As an alternative anticancer chemotherapeutic. AB - In the present study a novel water soluble double-decker phthalocyanine was synthesized and calf thymus DNA interaction of the synthesized double-decker phthalocyanine was investigated. 5-(3-pyridyl)-1,3,4-oxadiazole substituted phthalonitrile 1 was prepared by a nucleophilic displacement reaction of 4 nitrophthalonitrile with 5-(3-pyridyl)-1,3,4-oxadiazole-2-thiol. Lutetium(III) double-decker phthalocyanine 2 was prepared by cyclotetramerization of compound 1. Water soluble lutetium(III) double-decker phthalocyanine 3 was prepared with quaternarization of compound 2. The synthesized double-decker phthalocyanine and calf thymus DNA interaction was investigated with UV-vis titrimetric methods, gel electrophoresis, and viscosity measurements. The fluorometric ethidium bromide replacement assay was conducted to clarify the binding mode of water soluble double-decker phthalocyanine. The thermodynamic parameters for interaction, K, DeltaG0, DeltaH0 and DeltaS0 were calculated between the temperature ranges of 25 degrees C-75 degrees C. To the best of our knowledge, this is the first study about a double-decker phthalocyanine and DNA interaction. PMID- 26803445 TI - Sustained virological response with sofosbuvir and ledipasvir for hepatitis C virus genotype 5. PMID- 26803446 TI - Ledipasvir-sofosbuvir in patients with hepatitis C virus genotype 5 infection: an open-label, multicentre, single-arm, phase 2 study. AB - BACKGROUND: Data about the response of hepatitis C virus (HCV) genotype 5 to approved and experimental treatment regimens are scarce. We assessed the efficacy and safety of combination therapy with the NS5A inhibitor ledipasvir and the NS5B polymerase inhibitor sofosbuvir in patients with HCV genotype 5. METHODS: We did this open-label, multicentre, single-arm, phase 2 trial at five hospitals in France. Eligible patients were at least 18 years old and had chronic infection with HCV genotype 5, with plasma HCV RNA of at least 10,000 IU/mL. We used BLAST analyses of NS5B partial sequences to establish the genotype and subtype at screening. Patients were given a fixed-dose combination tablet of 90 mg ledipasvir and 400 mg sofosbuvir orally once per day for 12 weeks. The primary endpoint was the proportion of patients with a sustained viral response, defined as HCV RNA concentration less than 15 IU/mL at 12 weeks after the end of treatment (SVR12). We analysed efficacy and safety in all patients who received at least one dose of ledipasvir-sofosbuvir. This trial is registered with EudraCT, number 2013-003978-27, and with ClinicalTrials.gov, number NCT02081079. FINDINGS: From March 7 to June 10, 2014, we recruited 41 patients, including 21 who were treatment naive and 20 who were treatment experienced. All patients were of white ethnic origins. All 41 patients who started treatment completed the full 12 weeks of treatment and had undetectable HCV RNA at their final treatment visit. In the overall study population, 39 (95%, 95% CI 83-99) of 41 patients achieved SVR12. SVR12 was achieved by 20 (95%, 76-100) of the 21 patients who were treatment naive and 19 (95%, 75-100) of the 20 patients who were treatment experienced. Eight (89%) of nine patients with cirrhosis achieved SVR12, whereas 31 (97%) of the 32 patients without cirrhosis achieved SVR12. The two patients who did not reach SVR12 both had IL28B TT genotype and had viral relapse within 4 weeks of the end of treatment. The most common adverse events were asthenia (16 [39%] patients), headache (11 [27%] patients), and fatigue (four [10%] patients). One patient had a serious adverse event, worsening depression, which we judged to be unrelated to study treatment. INTERPRETATION: The oral regimen of ledipasvir sofosbuvir is an effective and well-tolerated treatment for patients with HCV genotype 5 infection who are treatment naive or treatment experienced. FUNDING: Gilead Sciences. PMID- 26803447 TI - [Red striae]. PMID- 26803448 TI - [Identifying clinical risk factors in recurrent idiopathic deep venous thrombosis]. AB - BACKGROUND AND OBJECTIVE: Oral anticoagulant therapy for more than 6 months in patients with an episode of idiopathic thromboembolic disease is controversial. The objective was to determine predictive clinical signs that identify patients at increased risk of thromboembolic recurrence after stopping anticoagulant therapy for 6 months after an episode of idiopathic deep vein thrombosis (DVT). PATIENTS AND METHODS: A prospective study which included 306 consecutive patients with a first episode of idiopathic DVT from June 2012 to June 2014. Predictor variables of recurrent thromboembolic disease and episodes of recurrence during follow-up of the patients (28.42 months) were collected. We performed a multivariate analysis to analyze possible predictors (P<.20) and an analysis of Kaplan-Meier to establish mean recurrence-free survival. RESULTS: We identified 91 episodes of residual vein thrombosis on follow-up of the patients (37.5% men and 20.3% women) (OR 1.84; 95% CI 1.25-2.71). In the Cox regression analysis stratified by gender, variables showed significant presence of hyperechoic thrombus (P=.001) in males, and persistence of residual thrombus in women (P=.046). The mean recurrence-free survival was shorter in both groups. CONCLUSIONS: The presence of echogenic thrombus in men and the existence of residual DVT in women were 2 clinical signs associated with increased risk of thromboembolic recurrence after stopping anticoagulant therapy for 6 months after an episode of idiopathic DVT in our study. PMID- 26803449 TI - [Importance of comorbidities in the anemia of COPD: Economic implications and 3 year survival analysis]. AB - INTRODUCTION: Anemia occurs commonly in COPD and is associated with a poor prognosis. The role of comorbidities in this is suspected but poorly characterized and the economic implications of anemia combined with COPD in France have not been studied. The healthcare resource utilization and cost impact of anemia remain to be investigated. METHODS: One hundred and fifty-one COPD patients attending a pulmonology outpatient department during a 6 months period were retrospectively selected if they had undergone a pulmonary function test, a blood gas analysis or a blood count. The Charlson comorbidity index, resource utilization and economic data from the year before the diagnosis of anemia were compared between anemic and non-anemic patients as well as 3-year survival analysis. RESULTS: The prevalence of anemia was 18.5% and was not influenced by GOLD stage. The identification of anemia was similar from blood gas results and full blood count analysis. Comorbidities - mainly cardiovascular - were found in 86% of the anemic patients. The Charlson index was 5.4+/-2 in the anemic group compared to 4.1+/-1.5 in the non-anemic group (P<0.01). The Charlson index was the only predictive factor of anemia using logistic regression analysis. The 3 year mortality was 36% in the anemic versus 7% in the non-anemic group (P<0.05). The main factor identified which predicted 3-year mortality was the presence of anemia using logistic regression. Healthcare costs the year prior to the diagnosis of anemia were not significantly different between groups, but there was a tendency to an increase in the cost of the hospitalizations in the anemic group. CONCLUSIONS: Anemia is easy to diagnose in COPD from the blood gas analysis. It is frequently linked to the presence of comorbidities - mainly cardiovascular diseases - and is the more important predictive factor of the 3 year mortality. There was a tendency towards an increase in the costs of hospitalizations in anemic patients but this remains to be confirmed in a larger economic study. PMID- 26803450 TI - RNA Editing: A Contributor to Neuronal Dynamics in the Mammalian Brain. AB - Post-transcriptional RNA modification by adenosine to inosine (A-to-I) editing expands the functional output of many important neuronally expressed genes. The mechanism provides flexibility in the proteome by expanding the variety of isoforms, and is a requisite for neuronal function. Indeed, targets for editing include key mediators of synaptic transmission with an overall significant effect on neuronal signaling. In addition, editing influences splice-site choice and miRNA targeting capacity, and thereby regulates neuronal gene expression. Editing efficiency at most of these sites increases during neuronal differentiation and brain maturation in a spatiotemporal manner. This editing-induced dynamics in the transcriptome is essential for normal brain development, and we are only beginning to understand its role in neuronal function. In this review we discuss the impact of RNA editing in the brain, with special emphasis on the physiological consequences for neuronal development and plasticity. PMID- 26803451 TI - [The cost of treating human immunodeficiency virus infection: Can reasonably be optimized?]. PMID- 26803452 TI - Adenoid cystic carcinoma of the larynx presenting with unusual subglottic mass: Case report. AB - A 33-year-old woman presented with an unusual subglottic bulging mass accompanied by prolonged cough and wheeze. Laryngeal endoscopy revealed a bilateral, symmetrical mass immediately below the vocal cords with marked airway obstruction. Chronic subglottic laryngitis with inflammation or another condition such as amyloidosis was initially suspected. Cervicothoracic computed tomography revealed an obvious reduction of laryngeal caliber caused by an engulfing mass extending from just under the vocal cords to the cricoid ring, which was associated with thyroid, arytenoid, and cricoid cartilage destruction. Histopathological diagnosis of a biopsy specimen collected via a tracheotomy revealed that the lesion was a cT4aN0M0 adenoid cystic carcinoma (ACC) originating from the laryngeal minor salivary glands. The patient was treated by total laryngectomy with elective bilateral neck dissection under general anesthesia. Gross inspection of resected tissue confirmed yellowish-white, solid tumor mainly circumferentially encompassing the lumina of the cricoid ring. The histopathological findings confirmed typical ACC accompanied by a predominant cribriform appearance with no evidence of lymph node metastasis. The patient remains well and free of recurrence or metastasis. We herein describe laryngeal ACC and discuss radiological images and the surgical pathology. PMID- 26803453 TI - Amount of Testosterone on Laundered Clothing After Use of Testosterone Topical 2% Solution by Healthy Male Volunteers. AB - INTRODUCTION: Testosterone 2% solution (Axiron) applied to armpit(s) is used for replacement therapy in men with a deficiency of endogenous testosterone. AIM: To determine the amount of testosterone on subjects' T-shirts 12 hours after applying testosterone solution, the residual testosterone on subjects' T-shirts after laundering, and the testosterone transferred to unworn textile items during laundering with worn T-shirts. METHODS: Healthy males >=18 years old applied 2 * 1.5 mL of testosterone 2% solution to both axillae (total testosterone dose: 120 mg) and dressed in cotton long-sleeved T-shirts after a >=3-minute waiting period. T-shirts were worn 12 hours before being removed and cut into halves, after which a 10 * 10 cm sample of each armpit area was excised for testosterone quantification before or after laundering with samples of unworn textiles. MAIN OUTCOME MEASURES: Testosterone on worn T-shirts before and after laundering, and on unworn textiles laundered with the worn T-shirts. RESULTS: Twelve subjects enrolled and completed, with only minor adverse events. Mean testosterone in unwashed worn T-shirts was 7603 MUg, with high between-subject variability (3359 MUg to 13,069 MUg), representing 13% of the dose to 1 armpit. Mean testosterone in worn, laundered T-shirts was 260 MUg (7.55 MUg to 1343 MUg), representing 3% of the dose to 1 armpit. Mean transferred testosterone to other textiles during laundering ranged from 69 MUg on texturized Dacron 56T Double to 10,402 MUg on 87/13 nylon/Lycra knit, representing 0.0382% to 5.78% of the dose to 1 armpit. CONCLUSION: Thirteen percent of the testosterone applied to axillae was transferred to T-shirts during wear. Ninety-seven percent of the transferred testosterone was removed from the T-shirts during washing, some of which was then absorbed to various degrees by other textiles. Clinical implications of these findings and biological activity of the remaining/transferred testosterone are unknown. PMID- 26803454 TI - Melatonin Improves Erectile Function in Rats With Chronic Lower Body Ischemia. AB - INTRODUCTION: Arterial occlusive disease is the leading cause of erectile dysfunction (ED). Using an established rat model we wanted to characterize the changes caused by atherosclerosis-induced chronic ischemia on penile structures and erectile function. AIM: To investigate the effect of melatonin on these parameters. METHODS: Adult male Sprague-Dawley rats were divided into control, arterial injury (AI) and AI with melatonin treatment groups. AI and AI-melatonin groups underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet following AI surgery for 8 weeks. AI-melatonin group rats received melatonin (20 mg/kg/day) orally for 8 weeks after AI. The control group received a regular diet. After 8 weeks, erectile function was tested. Corpus cavernosum (CC) tissues were processed for pharmacological and immunohistochemical studies, histological examination, and Western blotting. MAIN OUTCOME MEASURES: Apomorphine test was performed to evaluate erectile function. Organ bath study was performed to measure the CC-contraction induced by KCl and phenylephrine, and relaxation induced by electrical field stimulation (EFS) and sodium nitroprusside (SNP). RESULTS: The number of erectile responses was significantly lower in the AI group (2.5 +/- 0.5/hour) than in the control (5.0 +/- 0.7/hour) and in the melatonin-treated groups (5.0 +/- 0.3/hour). The responses to phenylephrine were lower in the AI-groups than in the controls, but there were no differences between control and AI-melatonin groups. SNP-induced relaxation in the AI-melatonin group was higher than in the AI, but lower than in control group. The EFS-elicited relaxation responses in the AI group were significantly lower than in the control and AI-melatonin groups. Compared to controls, CC tissues from the AI group showed significantly higher collagen content, and lower protein expression of eNOS and nNOS, and increased expression of iNOS. These changes were reduced or prevented by melatonin treatment. CONCLUSION: Treatment with melatonin reduced/prevented functional and morphological changes induced by chronic ischemia on penile structure and function. PMID- 26803455 TI - Percutaneous Tibial Nerve Stimulation Improves Female Sexual Function in Women With Overactive Bladder Syndrome. AB - INTRODUCTION: Percutaneous tibial nerve stimulation (PTNS) is an established treatment for overactive bladder (OAB), especially in women with other concomitant pelvic disorders, such as sexual impairment. AIM: To evaluate the impact of PTNS on female sexual dysfunction (FSD) in women undergoing PTNS for OAB and analyze the results. METHODS: An observational prospective study was conducted in two Italian centers. Consecutive women undergoing PTNS for dry OAB were enrolled from May 2013 to June 2014. All patients were asked to complete the Female Sexual Function Index (FSFI), the OAB short-form questionnaire, and a 24 hour bladder diary at baseline and 3 months later, at the end of the PTNS course. Patients with an FSFI total score no higher than 26.55 at inclusion were considered as presenting with FSD. Patients with an FSFI total score higher than 26.55 after treatment (if the increase in FSFI score was >=20%) were considered FSD objective responders. MAIN OUTCOME MEASURES: Sexuality was assessed using the FSFI. The 24-hour bladder diary and completed OAB short-form questionnaire were assessed before and after PTNS to evaluate OAB symptoms. RESULTS: Forty-one women were evaluable. Twenty-one of 41 women (51%; mean age = 51 +/- 10.67 years) were considered affected by FSD at inclusion. All FSFI domains showed statistically significant improvement in women with FSD (P < .05). In particular, 9 of 21 patients with FSD (43%) objectively responded (before treatment: mean FSFI total score = 18.11, range 10.8-26.3; after treatment: mean FSFI total score = 31.04, range 27.6-35). Also, women without FSD at baseline reported statistically significant improvement in their sexual function based on FSFI scores (P < .05). No significant correlations were seen between data questionnaires. CONCLUSION: PTNS improves sexual function in women with dry OAB. This amelioration is independent of urinary symptoms. Further studies are needed to confirm a possible role of PTNS in treating FSD. PMID- 26803456 TI - Assessment of Sexual Fantasies in Psychiatric Inpatients With Mood and Psychotic Disorders and Comorbid Personality Disorder Traits. AB - INTRODUCTION: Sexuality is an important aspect of quality of life and sexual fantasies comprise a normal part of human sexuality. However, the nature of sexuality and sexual fantasies of patients with mental illness remains an understudied area. AIM: To investigate the nature and frequency of sexual fantasies in psychiatric patients, the present study compared the frequency of four types of sexual fantasies across four different mood and psychotic diagnoses and three personality disorder clusters. METHODS: Study participants included 133 psychiatric inpatients recruited from an urban hospital. Sexual fantasies were compared across patients with schizophrenia, bipolar disorder, schizoaffective disorder, major depressive disorder and three nonclinical samples from the literature and then correlated with personality cluster scores. MAIN OUTCOME MEASURES: Subjects were administered the Structured Clinical Interview for DSM-IV for Axis I and for Axis II Disorders. Sexual fantasies were assessed by the Wilson Sexual Fantasies Questionnaire, which measures four types of sexual fantasies (exploratory, intimate, impersonal, and sadomasochistic). RESULTS: Within the entire sample, there were significant differences across sexual fantasy types, with subjects scoring highest on intimate sexual fantasies and then exploratory, impersonal, and sadomasochistic. There were no significant differences across mood and psychotic diagnostic groups for any of the sexual fantasy scales and the scores were within the normative range of nonclinical samples. Patients with high cluster B scores scored significantly higher on all four fantasy scales than those without. Patients with high cluster A scores scored lower on intimate fantasies, but there was no association between cluster C scores and sexual fantasies. The association between cluster B and sexual fantasies remained consistent across Structured Clinical Interview for DSM-IV for Axis I diagnoses (no interaction effect). CONCLUSION: Patients with severe mental illness report sexual fantasies that are largely affiliative in nature and consistent with normative patterns. This suggests that assessment and treatment of sexual issues in the mentally ill should be part of the clinical routine as it is in healthy individuals. PMID- 26803457 TI - Unprotected Intercourse and One-Night Stands: Impact of Sexual Excitation, Sexual Inhibition, and Atypical Sexual Arousal Patterns on Risky Sexual Behaviors in Women. AB - INTRODUCTION: Associations among sexual excitation, sexual inhibition, atypical sexual arousal patterns, and risky sexual behaviors have been reported in studies involving men and women. To date, longitudinal studies have not evaluated the predictive value of these propensities for future sexual behaviors in women. AIM: To investigate associations among sexual excitation, sexual inhibition, atypical sexual arousal patterns, and potentially risky sexual behaviors in women. METHODS: Overall, 2,214 women (mean age = 30.65 years, standard deviation = 9.91 years) participated in a baseline Web-based survey. The 1- and 2-year follow-up surveys included 396 and 382 participants, respectively. Correlational analyses and multiple linear regression analyses were conducted to analyze the relations between predictor and outcome variables. MAIN OUTCOME MEASURES: Number of partners, number of one-time sexual encounters, and number of partners with whom no condoms were used during the 12-month periods before each of the three data assessment points. RESULTS: All five lower-order factors of sexual excitation showed positive correlations and all three lower-order factors of sexual inhibition showed negative correlations with outcomes at baseline and follow-up. Atypical sexual arousal patterns, the tendency to become aroused in unusual sexual situations, and the importance of relationship factors, such as trust, for sexual arousal were the strongest predictors for sexual behaviors at baseline. These variables also predicted the number of sexual partners and the number of one-night stands at follow-up. CONCLUSION: The findings suggest that increased sexual arousal when experiencing negative mood might be a risk factor for potentially health-threatening sexual decisions and support the assumptions of the dual control model that sexual excitation is positively and sexual inhibition is negatively predictive of risky sexual behavior in women. PMID- 26803459 TI - [Cutaneous Mycobacterium tuberculosis infection associated with reactive paniculitis]. PMID- 26803458 TI - Black-white difference in long-term predictive power of self-rated health on all cause mortality in United States. AB - PURPOSE: Despite the well-established association between self-rated health (SRH) and mortality, limited information exists on Black-White differences in this link. Using a nationally representative sample of adults in the United States, the present study had four aims: (1) to assess whether the association between baseline SRH and all-cause mortality over a long follow-up differs for blacks and whites, (2) to test whether any race difference in the SRH-mortality link depends on how the SRH variable is treated (e.g., nominal, dichotomous, continuous), (3) to test if the SRH-mortality link or any differences in the association by race are explained by differences in objective health measures (chronic medical conditions [CMC]), and (4) to assess whether these associations vary by gender. METHODS: Data came from the Americans' Changing Lives Study, a nationally representative longitudinal cohort of U.S. adults 25 years and older with up to 25 years of follow-up. The study followed 3361 blacks or whites for all-cause mortality between 1986 and 2011. The predictor of interest was a single-item measure of SRH in 1986, treated as a nominal, dichotomous (fair/poor vs. excellent/very good/good), and continuous variable. Confounders included baseline age, education, income, depressive symptoms, and CMC. Race (black vs. white) was the focal effect modifier. We ran Cox proportional hazard models for the pooled sample and also stratified by race and gender, before and after adjusting for CMC. RESULTS: Regardless of how SRH was treated and for both men and women, we found significant interactions between race and SRH, indicating a stronger predictive role of SRH for all-cause mortality among whites compared to blacks. Before adjustment for chronic medical conditions, lower SRH was associated with higher risk of mortality among blacks and whites, but after adjustment, the SRH mortality association was no longer significant among blacks. CONCLUSIONS: Baseline SRH continues to predict long-term mortality among white but not black Americans after adjustment for chronic medical conditions at baseline, and these patterns are similar for men and women. Future research should test whether the differential predictive validity of SRH across race groups arises because SRH reflects different aspects of health of black and white Americans. PMID- 26803460 TI - [Lower urinary tract symptoms: An independent risk factor for cardiovascular disease]. PMID- 26803461 TI - [Noise and cardiovascular disease]. PMID- 26803462 TI - [Maternal and neonatal consequences of treated and untreated asymptomatic bacteriuria in pregnancy: A prospective cohort study with an embedded randomised controlled trial]. PMID- 26803463 TI - [Papular sarcoidosis of the knees]. PMID- 26803464 TI - A.I.S.F. 2016: Abstracts evaluation procedure. PMID- 26803465 TI - Actions from head to toe: An update on Bone/Body Morphogenetic Proteins in health and disease. AB - The pleiotropic actions of Bone Morphogenetic Proteins in many different tissues has led us to the conclusion that they may be viewed as Body Morphogenetic Proteins (BMPs). This is supported by a broad range of distinct BMP-related diseases. Here, we summarize highlights from the 10th international BMP conference, which took place from September 16th to 20th 2014 in Berlin. Attendees updated us on recently identified common and context-specific mechanisms of BMP signaling and function. This included for example new insights into BMP pro-domains, BMP receptors, role of BMPs in muscle and novel consequences of ACVRI mutations. Currently, new BMPs are entering clinical trials with the BMP pathway considered as a 'druggable' target. We conclude that various recent and ongoing approaches could indeed help patients in the near future. PMID- 26803466 TI - Intracerebral hemorrhage due to developmental venous anomalies. AB - Developmental venous anomalies (DVA) and cavernous malformations (CM) are a common form of mixed vascular malformation. The relationship between DVA, CM and hemorrhage is complicated. It is important to differentiate hemorrhagic CM and hemorrhagic DVA. A retrospective review of all patients with acute spontaneous intracerebral hemorrhages (ICH) between 1 May 2008 and 1 May 2013 was performed. ICH due to DVA or CM were identified and compared for demographic features, clinical symptoms, neurological deficits, and radiological findings. A total of 1706 patients with acute spontaneous ICH were admitted to our hospital during the study period. Among these, 10 (0.59%) were caused by DVA and 42 (2.47%) were caused by CM. No significant differences were found in age (p=0.252) or sex ratio (p=1.000) between the two groups. Compared with CM-induced ICH, DVA-induced ICH were characterized by cerebellar predominance (p=0.000) and less severe neurological deficits (p=0.008). Infratentorial hemorrhagic DVA are characterized by cerebellar predominance and benign clinical course. Infratentorial hemorrhagic CM are mainly located in the brainstem. DVA should be given suspected rather than CM when considering the etiology of a cerebellar hemorrhage, especially in young adults. PMID- 26803467 TI - Mycobacteria infect different cell types in the human lung and cause species dependent cellular changes in infected cells. AB - BACKGROUND: Mycobacterial infections remain a significant cause of morbidity and mortality worldwide. Due to limitations of the currently available model systems, there are still comparably large gaps in the knowledge about the pathogenesis of these chronic inflammatory diseases in particular with regard to the human host. Therefore, we aimed to characterize the initial phase of mycobacterial infections utilizing a human ex vivo lung tissue culture model designated STST (Short-Term Stimulation of Tissues). METHODS: Human lung tissues from 65 donors with a size of 0.5-1 cm(3) were infected each with two strains of three different mycobacterial species (M. tuberculosis, M. avium, and M. abscessus), respectively. In order to preserve both morphology and nucleic acids, the HOPE(r) fixation technique was used. The infected tissues were analyzed using histo- and molecular-pathological methods. Immunohistochemistry was applied to identify the infected cell types. RESULTS: Morphologic comparisons between ex vivo incubated and non-incubated lung specimens revealed no noticeable differences. Viability of ex vivo stimulated tissues demonstrated by TUNEL-assay was acceptable. Serial sections verified sufficient diffusion of the infectious agents deep into the tissues. Infection was confirmed by Ziel Neelsen-staining and PCR to detect mycobacterial DNA. We observed the infection of different cell types, including macrophages, neutrophils, monocytes, and pneumocytes-II, which were critically dependent on the mycobacterial species used. Furthermore, different forms of nuclear alterations (karyopyknosis, karyorrhexis, karyolysis) resulting in cell death were detected in the infected cells, again with characteristic species dependent differences. CONCLUSION: We show the application of a human ex vivo tissue culture model for mycobacterial infections. The immediate primary infection of a set of different cell types and the characteristic morphologic changes observed in these infected human tissues significantly adds to the current understanding of the initial phase of human pulmonary tuberculosis. Further studies are ongoing to elucidate the molecular mechanisms involved in the early onset of mycobacterial infections in the human lung. PMID- 26803468 TI - Cardiovascular magnetic resonance imaging of myocardial oedema following acute myocardial infarction: Is whole heart coverage necessary? AB - BACKGROUND: AAR measurement is useful when assessing the efficacy of reperfusion therapy and novel cardioprotective agents after myocardial infarction. Multi slice (Typically 10-12) T2-STIR has been used widely for its measurement, typically with a short axis stack (SAX) covering the entire left ventricle, which can result in long acquisition times and multiple breath holds. This study sought to compare 3-slice T2-short-tau inversion recovery (T2- STIR) technique against conventional multi-slice T2-STIR technique for the assessment of area at risk (AAR). METHODS: CMR imaging was performed on 167 patients after successful primary percutaneous coronary intervention. 82 patients underwent a novel 3-slice SAX protocol and 85 patients underwent standard 10-slice SAX protocol. AAR was obtained by manual endocardial and epicardial contour mapping followed by a semi- automated selection of normal myocardium; the volume was expressed as mass (%) by two independent observers. RESULTS: 85 patients underwent both 10-slice and 3 slice imaging assessment showing a significant and strong correlation (intraclass correlation coefficient = 0.92;p < 0.0001) and a low Bland-Altman limit (mean difference -0.03 +/- 3.21%, 95% limit of agreement,- 6.3 to 6.3) between the 2 analysis techniques. A further 82 patients underwent 3-slice imaging alone, both the 3-slice and the 10-slice techniques showed statistically significant correlations with angiographic risk scores (3-slice to BARI r = 0.36, 3-slice to APPROACH r = 0.42, 10-slice to BARI r = 0.27, 10-slice to APPROACH r = 0.46). There was low inter-observer variability demonstrated in the 3-slice technique, which was comparable to the 10-slice method (z = 1.035, p = 0.15). Acquisition and analysis times were quicker in the 3-slice compared to the 10-slice method (3 slice median time: 100 seconds (IQR: 65-171 s) vs. (10-slice time: 355 seconds (IQR: 275-603 s); p < 0.0001. CONCLUSIONS: AAR measured using 3-slice T2-STIR technique correlates well with standard 10-slice techniques, with no significant bias demonstrated in assessing the AAR. The 3-slice technique requires less time to perform and analyse and is therefore advantageous for both patients and clinicians. PMID- 26803469 TI - Gender differences in metabolic syndrome components among the Korean 66-year-old population with metabolic syndrome. AB - BACKGROUND: Gender is thought to be an important factor in metabolic syndrome and its outcomes. Despite a number of studies that have demonstrated differences in metabolism and its components that are dependent on gender, limited information about gender differences on the characteristics of metabolic syndrome and its components is available regarding the Korean old adult population. This study aimed to identify gender differences in characteristics of the metabolic syndrome and other risk factors for cardiovascular disease. METHODS: Secondary analysis of data from a nationwide cross-sectional survey for health examination at the time of transitioning from midlife to old age was performed. Multiple logistic regression models were used to estimate adjusted odds ratios and 95% confidence intervals for gender differences among the Korean 66-year-old population with metabolic syndrome. RESULTS: Gender differences in metabolic syndrome components that contributed to the diagnosis of metabolic syndrome were identified. In males, the most common component was high blood sugar levels (87.5%), followed by elevated triglyceride levels (83.5%) and high blood pressure (83.1%). In females, the most commonly identified component was elevated triglyceride levels (79.0%), followed by high blood sugar levels (78.6%) and high blood pressure (78.5%). Gender differences for other risk factors for cardiovascular disease, including family history, health habits, and body mass index were observed. CONCLUSIONS: Gender-specific public health policies and management strategies to prevent cardiovascular disease among the older adult population should be developed for Koreans undergoing the physiological transition to old age. PMID- 26803470 TI - A high throughput Cre-lox activated viral membrane fusion assay identifies pharmacological inhibitors of HIV entry. AB - Enveloped virus entry occurs when viral and cellular membranes fuse releasing particle contents into the target cell. Human immunodeficiency virus (HIV) entry occurs by cell-free virus or virus transferred between infected and uninfected cells through structures called virological synapses. We developed a high throughput cell-based assay to identify small molecule inhibitors of cell-free or virological synapse-mediated entry. An HIV clone carrying Cre recombinase as a Gag-internal gene fusion releases active Cre into cells upon viral entry activating a recombinatorial gene switch changing dsRed to GFP-expression. A screen of a 1998 known-biological profile small molecule library identified pharmacological HIV entry inhibitors that block both cell-free and cell-to-cell infection. Many top hits were noted as HIV inhibitors in prior studies, but not previously recognized as entry antagonists. Modest therapeutic indices for simvastatin and nigericin were observed in confirmatory HIV infection assays. This robust assay is adaptable to study HIV and heterologous viral pseudotypes. PMID- 26803472 TI - Comparison of steam sterilization conditions efficiency in the treatment of Infectious Health Care Waste. AB - Many studies show that the treatment of Infectious Health Care Waste (IHCW) in steam sterilization devices at usual operating standards does not allow for proper treatment of Infectious Health Care Waste (IHCW). Including a grinding component before sterilization allows better waste sterilization, but any hard metal object in the waste can damage the shredder. The first objective of the study is to verify that efficient IHCW treatment can occur at standard operating parameters defined by the contact time-temperature couple in steam treatment systems without a pre-mixing/fragmenting or pre-shredding step. The second objective is to establish scientifically whether the standard operation conditions for a steam treatment system including a step of pre mixing/fragmenting were sufficient to destroy the bacterial spores in IHCW known to be the most difficult to treat. Results show that for efficient sterilization of dialysis cartridges in a pilot 60L steam treatment system, the process would require more than 20 min at 144 degrees C without a pre-mixing/fragmenting step. In a 720L steam treatment system including pre-mixing/fragmenting paddles, only 10 min at 144 degrees C are required to sterilize IHCW proved to be sterilization challenges such as dialysis cartridges and diapers in normal conditions of rolling. PMID- 26803471 TI - Modulating immunogenic properties of HIV-1 gp41 membrane-proximal external region by destabilizing six-helix bundle structure. AB - The C-terminal alpha-helix of gp41 membrane-proximal external region (MPER; (671)NWFDITNWLWYIK(683)) encompassing 4E10/10E8 epitopes is an attractive target for HIV-1 vaccine development. We previously reported that gp41-HR1-54Q, a trimeric protein comprised of the MPER in the context of a stable six-helix bundle (6HB), induced strong immune responses against the helix, but antibodies were directed primarily against the non-neutralizing face of the helix. To better target 4E10/10E8 epitopes, we generated four putative fusion intermediates by introducing double point mutations or deletions in the heptad repeat region 1 (HR1) that destabilize 6HB in varying degrees. One variant, HR1-?10-54K, elicited antibodies in rabbits that targeted W672, I675 and L679, which are critical for 4E10/10E8 recognition. Overall, the results demonstrated that altering structural parameters of 6HB can influence immunogenic properties of the MPER and antibody targeting. Further exploration of this strategy could allow development of immunogens that could lead to induction of 4E10/10E8-like antibodies. PMID- 26803473 TI - Conceptual framework for the study of food waste generation and prevention in the hospitality sector. AB - Food waste has significant detrimental economic, environmental and social impacts. The magnitude and complexity of the global food waste problem has brought it to the forefront of the environmental agenda; however, there has been little research on the patterns and drivers of food waste generation, especially outside the household. This is partially due to weaknesses in the methodological approaches used to understand such a complex problem. This paper proposes a novel conceptual framework to identify and explain the patterns and drivers of food waste generation in the hospitality sector, with the aim of identifying food waste prevention measures. This conceptual framework integrates data collection and analysis methods from ethnography and grounded theory, complemented with concepts and tools from industrial ecology for the analysis of quantitative data. A case study of food waste generation at a hotel restaurant in Malaysia is used as an example to illustrate how this conceptual framework can be applied. The conceptual framework links the biophysical and economic flows of food provisioning and waste generation, with the social and cultural practices associated with food preparation and consumption. The case study demonstrates that food waste is intrinsically linked to the way we provision and consume food, the material and socio-cultural context of food consumption and food waste generation. Food provisioning, food consumption and food waste generation should be studied together in order to fully understand how, where and most importantly why food waste is generated. This understanding will then enable to draw detailed, case specific food waste prevention plans addressing the material and socio-economic aspects of food waste generation. PMID- 26803474 TI - A novel device for accurate and efficient testing for vision-threatening diabetic retinopathy. AB - AIMS: To evaluate the performance of the RETeval device, a handheld instrument using flicker electroretinography (ERG) and pupillography on undilated subjects with diabetes, to detect vision-threatening diabetic retinopathy (VTDR). METHODS: Performance was measured using a cross-sectional, single armed, non interventional, multi-site study with Early Treatment Diabetic Retinopathy Study 7-standard field, stereo, color fundus photography as the gold standard. The 468 subjects were randomized to a calibration phase (80%), whose ERG and pupillary waveforms were used to formulate an equation correlating with the presence of VTDR, and a validation phase (20%), used to independently validate that equation. The primary outcome was the prevalence-corrected area under the receiver operating characteristic (ROC) curve for the detection of VTDR. RESULTS: The area under the ROC curve was 0.86 for VTDR. With a sensitivity of 83%, the specificity was 78% and the negative predictive value was 99%. The average testing time was 2.3 min. CONCLUSIONS: With a VTDR prevalence similar to that in the U.S., the RETeval device will identify about 75% of the population as not having VTDR with 99% accuracy. The device is simple to use, does not require pupil dilation, and has a short testing time. PMID- 26803475 TI - Discordance in the levels of hemoglobin A1C and glycated albumin: Calculation of the glycation gap based on glycated albumin level. AB - OBJECTIVE: The glycation gap (G-gap) is an empirical measure of the extent of the difference between HbA1C and fructosamine levels. Several studies have shown that the presence of a G-gap is linked to diabetic nephropathy, but possible artifacts caused by dependence of the fructosamine level on the extent of serum protein metabolism require careful consideration. We investigated the consistency of G gaps measured by assaying glycated albumin (GA) levels to identify factors associated with G-gap variations. METHOD: A total of 457 pairs of observations, like an HbA1c and GA measurement at the same clinic visit, were obtained from 170 Korean patients with type 2 diabetes. HbA1c and GA levels were measured simultaneously in two or three separate occasions. Each G-gap was calculated as the difference between the measured HbA1c level and that predicted by the GA level. All patients underwent abdominal computed tomography, and the areas of subcutaneous and visceral fat were measured. RESULTS: The G-gaps were all significantly inter-correlated over time (gamma=0.755, P<0.001).The direction of each G-gap was consistent. The body mass index (BMI), visceral fat area, and the estimated glomerular filtration rate (eGFR) increased linearly from the lowest to the highest G-gap quartile (all P values <0.05). Upon multivariate analysis, both visceral fat area and the eGFR were significantly associated with a G-gap. CONCLUSIONS: A G-gap determined using GA measurements is consistent within an individual over time. The G-gap is associated with visceral fat and kidney function in patients with type 2 diabetes. PMID- 26803476 TI - Results of a Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with Mitomycin C Versus Bacillus Calmette-Guerin for Adjuvant Treatment of Patients with Intermediate- and High-risk Non-Muscle-invasive Bladder Cancer. AB - BACKGROUND: Despite adjuvant intravesical therapy, recurrences in non-muscle invasive bladder cancer (NMIBC) are still high; therefore, new treatment options are needed. The use of chemohyperthermia (CHT) as an alternative treatment is expanding in Europe. To date, however, there has been a lack of prospective randomised data. OBJECTIVE: To compare CHT using mitomycin C (MMC) with bacillus Calmette-Guerin (BCG) as adjuvant treatment for intermediate- and high-risk NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Between 2002 and 2012, 190 NMIBC patients were randomised in this controlled, open-label, multicentre trial for 1 yr CHT (six weekly treatments and six maintenance treatments) and 1-yr BCG immunotherapy (six weekly treatments and three weekly maintenance treatments at months 3, 6, and 12). Patients and physicians giving the interventions were aware of assignment. This study is registered with ClinicalTrials.gov (NCT00384891). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was 24-mo recurrence-free survival (RFS) in the intention-to-treat (ITT) and per-protocol (PP) analyses in all papillary NMIBC patients (n=147). Analyses were done with the log-rank test and Fisher exact test. All tests were two-sided. RESULTS AND LIMITATIONS: The 24-mo ITT RFS was 78.1% in the CHT group compared with 64.8% in the BCG group (p=0.08). The 24-mo RFS in the PP analysis was 81.8% in the CHT group compared with 64.8% in the BCG group (p=0.02). Progression rates were <2% in both groups. Regarding the side-effects, no new safety concerns were identified. A concern is that this study closed prematurely and thus is underpowered. Furthermore, blinding of treatment for patients and physicians was impossible; this may have resulted in unavoidable bias. CONCLUSIONS: CHT is a safe and effective treatment option in patients with intermediate- and high-risk papillary NMIBC. A significantly higher 24-mo RFS in the CHT group was seen in the PP analysis. Based on the results above, CHT is an option for BCG therapy as adjuvant treatment for intermediate- and high-risk papillary NMIBC. PATIENT SUMMARY: Recurrences in non-muscle-invasive bladder cancer are common, despite adjuvant therapies. We compared 24-mo recurrence-free survival (RFS) with chemohyperthermia (CHT) versus bacillus Calmette-Guerin (BCG) therapy. According to these data, CHT therapy appears to be safe and has higher 24-mo RFS than BCG therapy. PMID- 26803477 TI - The Challenge for Urologists Is to Screen, Detect, and Treat Prostate Cancer "Smarter": Will Ablative Technology Result in Smarter Treatment? PMID- 26803478 TI - Genomic Alterations in Liquid Biopsies from Patients with Bladder Cancer. AB - BACKGROUND: At least half of the patients diagnosed with non-muscle-invasive bladder cancer (NMIBC) experience recurrence and approximately 15% will develop progression to muscle invasive or metastatic disease. Biomarkers for disease surveillance are urgently needed. OBJECTIVE: Development of assays for surveillance using genomic variants in cell-free tumour DNA from plasma and urine. DESIGN, SETTING, AND PARTICIPANTS: Retrospective pilot study of 377 samples from 12 patients with recurrent or progressive/metastatic disease. Three next-generation sequencing methods were applied and somatic variants in DNA from tumour, plasma, and urine were subsequently monitored by personalised assays using droplet digital polymerase chain reaction (ddPCR). Samples were collected from 1994 to 2015, with up to 20 yr of follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Progression to muscle-invasive or metastatic bladder cancer; t test for ddPCR data. RESULTS AND LIMITATIONS: We developed from one to six personalised assays per patient. Patients with progressive disease showed significantly higher levels of tumour DNA in plasma and urine before disease progression, compared with patients with recurrent disease (p=0.032 and 1.3*10( 6), respectively). Interestingly, tumour DNA was detected in plasma and urine in patients with noninvasive disease, being no longer detectable in disease-free patients. A significant level of heterogeneity was observed for each patient; this could be due to tumour heterogeneity or assay performance. CONCLUSIONS: Cell free tumour DNA can be detected in plasma and urine, even in patients with noninvasive disease, with high levels of tumour DNA detectable before progression, especially in urine samples. Personalised assays of genomic variants may be useful for disease monitoring. PATIENT SUMMARY: Tumour DNA can be detected in blood and urine in early and advanced stages of bladder cancer. Measurement of these highly tumour-specific biomarkers may represent a novel diagnostic tool to indicate the presence of residual disease or to discover aggressive forms of bladder cancer early in the disease course. PMID- 26803479 TI - Multiprobe molecular imaging of an NMDA receptor hypofunction rat model for glutamatergic dysfunction. AB - There are many indications of a connection between abnormal glutamate transmission through N-methyl-d-aspartate (NMDA) receptor hypofunction and the occurrence of schizophrenia. The importance of metabotropic glutamate receptor subtype 5 (mGluR5) became generally recognized due to its physical link through anchor proteins with NMDAR. Neuroinflammation as well as the kynurenine (tryptophan catabolite; TRYCAT) pathway are equally considered as major contributors to the pathology. We aimed to investigate this interplay between glutamate release, neuronal activation and inflammatory markers, by using small animal positron emission tomography (PET) in a rat model known to induce schizophrenia-like symptoms. Daily intraperitoneal injection of MK801 or saline were administered to induce the model together with N-Acetyl-cysteine (NAc) or saline as the treatment in 24 male Sprague Dawley rats for one month. Biweekly in vivo [(11)C]-ABP688 microPET was performed together with mGluR5 immunohistochemistry. Simultaneously, weekly in vivo [(18)F]-FDG microPET imaging data for glucose metabolism was acquired and microglial activation was investigated with biweekly in vivo [(18)F]-PBR111 scans versus OX42 immunohistochemistry. Finally, plasma samples were analyzed for TRYCAT metabolites. We show that chronic MK801 administration (and thus elevated endogenous glutamate) causes significant tissue loss in rat brain, enhances neuroinflammatory pathways and may upregulate mGluR5 expression. PMID- 26803480 TI - Low sulfide levels and a high degree of cystathionine beta-synthase (CBS) activation by S-adenosylmethionine (SAM) in the long-lived naked mole-rat. AB - Hydrogen sulfide (H2S) is a gaseous signalling molecule involved in many physiological and pathological processes. There is increasing evidence that H2S is implicated in aging and lifespan control in the diet-induced longevity models. However, blood sulfide concentration of naturally long-lived species is not known. Here we measured blood sulfide in the long-lived naked mole-rat and five other mammalian species considerably differing in lifespan and found a negative correlation between blood sulfide and maximum longevity residual. In addition, we show that the naked mole-rat cystathionine beta-synthase (CBS), an enzyme whose activity in the liver significantly contributes to systemic sulfide levels, has lower activity in the liver and is activated to a higher degree by S adenosylmethionine compared to other species. These results add complexity to the understanding of the role of H2S in aging and call for detailed research on naked mole-rat transsulfuration. PMID- 26803481 TI - Melatonin and L-carnitin improves endothelial disfunction and oxidative stress in Type 2 diabetic rats. AB - Vascular dysfunction is thought to play a major role in the development of diabetic cardiovascular disease. The roles of endothelial dysfunction, oxidative stress, and dyslipidemia will be considered. Melatonin as well as L-carnitine were shown to possess strong antioxidant properties. Diabetes induced with high fat diet (for 8 weeks) and multipl low doses intraperitoneal injection of STZ (twice, 30mg/kg/d i.p). The diabetic animals were randomly assigned to one of the experimental groups as follows: Control group (C), high fat diet (HFD), STZ induced diabetic group (HFD+STZ) , HFD+STZ diabetic group received melatonin (10mg/kg/d i.p), HFD+STZ diabetic group received L-carnitine (0.6g/kg/d i.p), and HFD+STZ diabetic group received glibenclamide (5mg/kg/d, oral). The serum fasting blood glucose, insulin, total cholesterol, HDL- cholesterol, LDL-cholesterol, triglyceride and malondialdehyde (MDA) levels were tested. Acetylcholine induced endothelium-dependent relaxation and sodium nitroprusside induced endothelium independent relaxation were measured in aortas for estimating endothelial function. Also, glutathione peroxidase (GPx), superoxide dismutase (SOD) and nitric oxide (NO) levels activities were determined in rat liver. According to our results melatonin and L-carnitine treatment decreased fasting blood glucose, total cholesterol, and LDL levels. MDA levels significantly decreased with the melatonin treatment whereas SOD levels were not significantly changed between the groups. The results suggest that especially melatonin restores the vascular responses and endothelial dysfunction in diabetes. PMID- 26803482 TI - Ethnic differences in all-cause mortality rates in Kazakhstan. AB - OBJECTIVES: This article explores mortality rates in Kazakhstan by ethnic group and some of the potential lifestyle factors that might help to explain the observed differences on a population level. STUDY DESIGN: Repeated cross sectional data analysis. METHODS: We calculated age-standardized mortality rates from all causes by ethnic group, gender and age for 2009-2012. We analysed data on self-reported alcohol and tobacco consumption and other lifestyle factors from the nationally representative 5th National Behavior Study, conducted in 2012. RESULTS: Age-standardized all-cause mortality rates are generally much higher among ethnic Russians than among ethnic Kazakhs, both among women and men and in rural as well as urban areas. These differences are most pronounced in the age group 20-59 years. Information on self-reported alcohol consumption and smoking by ethnic group, gender and age shows major differences between ethnic groups, with consistently higher rates of alcohol consumption and smoking among ethnic Russians, both in women and men and across all adult age groups. CONCLUSIONS: Policies to improve the health of the population of Kazakhstan must take account of ethnic differences. PMID- 26803483 TI - Breast screening knowledge and barriers among under/never screened women. PMID- 26803484 TI - Synaptic plasticity model of therapeutic sleep deprivation in major depression. AB - Therapeutic sleep deprivation (SD) is a rapid acting treatment for major depressive disorder (MDD). Within hours, SD leads to a dramatic decrease in depressive symptoms in 50-60% of patients with MDD. Scientifically, therapeutic SD presents a unique paradigm to study the neurobiology of MDD. Yet, up to now, the neurobiological basis of the antidepressant effect, which is most likely different from today's first-line treatments, is not sufficiently understood. This article puts the idea forward that sleep/wake-dependent shifts in synaptic plasticity, i.e., the neural basis of adaptive network function and behavior, represent a critical mechanism of therapeutic SD in MDD. Particularly, this article centers on two major hypotheses of MDD and sleep, the synaptic plasticity hypothesis of MDD and the synaptic homeostasis hypothesis of sleep-wake regulation, and on how they can be integrated into a novel synaptic plasticity model of therapeutic SD in MDD. As a major component, the model proposes that therapeutic SD, by homeostatically enhancing cortical synaptic strength, shifts the initially deficient inducibility of associative synaptic long-term potentiation (LTP) in patients with MDD in a more favorable window of associative plasticity. Research on the molecular effects of SD in animals and humans, including observations in the neurotrophic, adenosinergic, monoaminergic, and glutamatergic system, provides some support for the hypothesis of associative synaptic plasticity facilitation after therapeutic SD in MDD. The model proposes a novel framework for a mechanism of action of therapeutic SD that can be further tested in humans based on non-invasive indices and in animals based on direct studies of synaptic plasticity. Further determining the mechanisms of action of SD might contribute to the development of novel fast acting treatments for MDD, one of the major health problems worldwide. PMID- 26803485 TI - Transurethral front-firing Greenlight bladder autoaugmentation for bladder contracture: technique and clinical outcomes. AB - OBJECTIVE: To describe a novel transurethral front-firing Greenlight bladder autoaugmentation for the treatment of bladder contracture and report initial clinical outcomes. METHODS: Between April 2014 and August 2015, five patients diagnosed with contracted bladder were all refractory to conservative treatment and received novel transurethral autoaugmentation. CT scan and urodynamics examination were conducted before operation for disease assessment. Mucosal and muscular layers of bladder wall in fundus were incised vertically and horizontally with front-firing Greenlight laser to enlarge bladder capacity in the operation. Imaging examination and periodical urodynamics study were performed to evaluate the clinical outcomes of the procedure in postoperative follow-up. RESULTS: Transurethral front-firing Greenlight bladder autoaugmentation was performed successfully on all the patients. The mean operative time was 59 min (range 52-65 min) with no significant blood loss. Urodynamic parameters of these patients after operation improved significantly compared with those before operation. Average maximum cystometric capacity (Vmax) increased from 91.2 to 333 ml (p < 0.01), average maximum flow rate (Qmax) ascended from 12.6 to 18.62 ml/min (p < 0.01), and average flow rate (Q(ave)) also increased from 5.74 to 13.18 ml/min (p < 0.01). At the last follow-up, all the patients could void spontaneously with good bladder emptying and their symptoms improved significantly. CONCLUSION: Our novel transurethral front-firing Greenlight bladder autoaugmentation is a safe and effective treatment for contracted bladders. Future studies with larger sample size and long-term follow up are needed to confirm our findings. PMID- 26803487 TI - Erratum to: Frosted branch angiitis complicated by retinal vein occlusion: clinical course and long-term visual outcome. PMID- 26803486 TI - Meta-Analysis of the COMT Val158Met Polymorphism in Major Depressive Disorder: Effect of Ethnicity. AB - The COMT (catechol-O-methyltransferase) Val158Met polymorphism (rs4680) is a potential susceptibility variant for major depressive disorder (MDD). Although many genetic studies have examined the association between MDD and this polymorphism, the results were inconclusive. In the present study, we conducted a series of meta-analyses of samples consisting of 2905 MDD cases and 2403 controls with the goal of determining whether this variant indeed has any effect on MDD. We revealed a significant association in the comparison of Val/Val + Val/Met vs. Met/Met (OR =1.180; 95 % CI = 1.019, 1.367; P = 0.027), Val/Met vs. Val/Val (OR =1.18; 95 % CI = 1.038, 1.361; P = 0.013), and Val/Met vs. Met/Met (OR =1.229; 95 % CI = 1.053, 1.435; P = 0.009). Further meta-analyses of samples with European ancestry demonstrated a significant association of this SNP with MDD susceptibility in Val/Val + Val/Met vs. Met/Met (OR =1.231, 95 % CI = 1.046, 1.449; P = 0.013) and Val/Met vs. Met/Met (OR =1.284, 95 % CI = 1.050, 1.484; P = 0.012). For the samples with East Asian ancestry, we found a significant association in both allelic (Val vs. Met: OR =0.835; 95 % CI = 0.714, 0.975; P = 0.023) and genotypic (Met/Met + Val/Met vs. Val/Val: OR =1.431, 95 % CI = 1.143, 1.791; P = 0.002; Val/Met vs. Val/Val: OR =1.482, 95 % CI = 1.171, 1.871; P = 0.001) analyses. No evidence of heterogeneity among studies or publication bias was observed. Together, our results indicate that the COMT Val158Met polymorphism is a vulnerability factor for MDD with distinct effects in different ethnic populations. PMID- 26803488 TI - Paravascular abnormalities in eyes with idiopathic epiretinal membrane. AB - PURPOSE: The purpose was to investigate the paravascular abnormalities (PVA) around the retinal vascular arcades and their post-operative evolution in eyes with epiretinal membranes (ERM). METHODS: This is an observational case series. Fifty-seven eyes of 55 patients with concurrent PVA and ERM were studied (study group). Forty-one eyes in 41 patients with ERM but no PVA served as controls. Multiple optical coherence tomography (OCT) scans were made along the upper and lower arcades and across the fovea in each patient. Serial fundus photography and OCT scans were performed in eyes receiving an operation. All surgeries were performed by one surgeon. The incidence and location of paravascular retinal cysts, deep cystic spaces underneath the vessels, and paravascular retinal defects, as well as vitreoretinal interface changes, were determined and correlated with macular thickness. RESULTS: In the study group, paravascular retinal cysts were detected in 57 eyes (100 %), deep cystic spaces in nine eyes (15.8 %), and paravascular lamellar holes in 31 eyes (54.4 %). No case had a full thickness hole. ERM adhesion to the PVA was noted in 16 eyes (28.1 %) and internal limiting membrane (ILM) changes over the PVA in 22 eyes (38.6 %). Compared with the control, the study group had significantly increased macular thickness. PVA, except lamellar holes, disappeared or decrease in severity after ERM and ILM removal surgery. CONCLUSION: Different types of PVA are relatively common in eyes with ERM. Our findings suggest that PVA may develop secondary to ERM-induced macular thickening. Except for lamellar holes, most lesions decrease following an operation. PMID- 26803489 TI - Safety and efficacy of selective retina therapy (SRT) for the treatment of diabetic macular edema in Korean patients. AB - PURPOSE: Selective retina therapy (SRT) stimulates retinal pigment epithelium (RPE) cell migration and proliferation into irradiated areas. The objective of this study was to evaluate the efficacy and safety of SRT in Korean patients with clinically significant diabetic macular edema (DME). METHODS: Prospective non randomized interventional case series study. Twenty-three eyes of 21 patients with clinically significant DME were treated with SRT and followed for 6 months. Patients underwent an evaluation of best corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Microperimetry was employed to measure macular sensitivity within the central 10 degrees field, and the central macular thickness (CMT) and maximum macular thickness (MMT) were measured. RESULTS: An improvement in BCVA of one to two ETDRS lines was observed in 41.2 % of patients and an improvement of greater than two lines in 29.4 %. Although there was no significant change in CMT (P > 0.05), MMT decreased from 465.8 +/- 87.4 MUm to 434.3 +/- 83.9 MUm (P = 0.006), and mean macular sensitivity increased from 20.8 +/- 3.4dB to 22.5 +/- 3.5dB (P = 0.02). CONCLUSIONS: The gains in BCVA and improvement in macular sensitivity demonstrated that SRT may be used as an effective and safe treatment modality in Korean patients with clinically significant DME. PMID- 26803491 TI - Salvage radiotherapy in prostate cancer patients. Planning, treatment response and prognosis using (11)C-choline PET/CT. AB - OBJECTIVE: To assess the prognostic value of the therapeutic response by (11)C choline PET/CT in prostate cancer patients with biochemical recurrence in which (11)C-choline PET/CT indicated radio-guided radiotherapy. METHODS: The study included 37 patients initially treated with prostatectomy, who were treated due to biochemical recurrence. (11)C-choline PE/CT detected infra-diaphragmatic lymph node involvement. All were selected for intensity modulated radiation therapy, escalating the dose according to the PET findings. One year after treatment patients underwent PSA and (11)C-choline PET/CT categorizing response (complete/partial/progression). Clinical/biochemical/image monitoring was performed until appearance of second relapse or 36 months in disease-free patients. RESULTS: (11)C-choline PET/CT could detect lymph nodes in all 37 patients. They were 18 (48.6%) of more than a centimetre in size and 19 (51.3%) with no pathological CT morphology: 9 (24.3%) with positive lymph nodes of around one centimetre and 10 (27.0%) only less than a centimetre in size. The response by (11)C-choline PET/CT was categorised one year after radiotherapy: 16 patients (43.2%) complete response; 15 (40.5%) partial response, and 6 (16.2%) progression. The response was concordant between the PSA result and (11)C-choline PET/CT in 32 patients (86.5%), and discordant in five (13.5%). New recurrence was detected in 12 patients (80%) with partial response, and 5 (31.2%) with complete response. The mean time to recurrence was 9 months after partial response, and 18 months after complete response (significant difference, p<.0001). CONCLUSION: (11)C-choline PET/CT allows the selection of patients with recurrent prostate cancer candidates for radiotherapy and to plan the technique. The evaluation of therapeutic response by (11)C-choline PET/CT has prognostic significance. PMID- 26803492 TI - A heritable form of SMARCE1-related meningiomas with important implications for follow-up and family screening. AB - Childhood meningiomas are rare. Recently, a new hereditary tumor predisposition syndrome has been discovered, resulting in an increased risk for spinal and intracranial clear cell meningiomas (CCMs) in young patients. Heterozygous loss of-function germline mutations in the SMARCE1 gene are causative, giving rise to an autosomal dominant inheritance pattern. We report on an extended family with a pediatric CCM patient and an adult CCM patient and several asymptomatic relatives carrying a germline SMARCE1 mutation, and discuss difficulties in genetic counseling for this heritable condition. Because of the few reported cases so far, the lifetime risk of developing meningiomas for SMARCE1 mutation carriers is unclear and the complete tumor spectrum is unknown. There is no surveillance guideline for asymptomatic carriers nor a long-term follow-up recommendation for SMARCE1-related CCM patients as yet. Until more information is available about the penetrance and tumor spectrum of the condition, we propose the following screening advice for asymptomatic SMARCE1 mutation carriers: neurological examination and MRI of the brain and spine, yearly from diagnosis until the age of 18 and once every 3 years thereafter, or in between if there are clinical symptoms. This advice can also be used for long-term patient follow-up. More data is needed to optimize this proposed screening advice. PMID- 26803494 TI - Restrained Phosphatidylcholine Synthesis in a Cellular Model of Down's Syndrome is Associated with the Overexpression of Dyrk1A. AB - Aberrant formation of the cerebral cortex could be attributed to the lack of suitable substrates that direct the migration of neurons. Previous work carried out at our laboratory has shown that oleic acid is a neurotrophic factor. In order to characterize the effect of oleic acid in a cellular model of Down's syndrome (DS), here, we used immortalized cell lines derived from the cortex of trisomy Ts16 and euploid mice. We report that in the plasma membrane of euploid cells, an increase in phosphatidylcholine concentrations occurs in the presence of oleic acid. However, in trisomic cells, oleic acid failed to increase phosphatidylcholine incorporation into the plasma membrane. Gene expression analysis of trisomic cells revealed that the phosphatidylcholine biosynthetic pathway was deregulated. Taken together, these results suggest that the overdose of specific genes in trisomic lines delays differentiation in the presence of oleic acid. The dual-specificity tyrosine (Y) phosphorylation-regulated kinase 1A (DYRK1A) gene is located on human chromosome 21. DYRK1A contributes to intellectual disability and the early onset of Alzheimer's disease in DS patients. Here, we explored the potential role of Dyrk1A in the reduction of phosphatidylcholine concentrations in trisomic cells in the presence of oleic acid. The downregulation of Dyrk1A by small interfering RNA (siRNA) in trisomic cells returned phosphatidylcholine concentrations up to similar levels to those of euploid cells in the presence of oleic acid. Thus, our results highlight the role of Dyrk1A in brain development through the modulation of phosphatidylcholine location, levels and synthesis. PMID- 26803493 TI - SK3 Channel Overexpression in Mice Causes Hippocampal Shrinkage Associated with Cognitive Impairments. AB - The dysfunction of the small-conductance calcium-activated K+ channel SK3 has been described as one of the factors responsible for the progress of psychoneurological diseases, but the molecular basis of this is largely unknown. This report reveals through use of immunohistochemistry and computational tomography that long-term increased expression of the SK3 small-conductance calcium-activated potassium channel (SK3-T/T) in mice induces a notable bilateral reduction of the hippocampal area (more than 50 %). Histological analysis showed that SK3-T/T mice have cellular disarrangements and neuron discontinuities in the hippocampal formation CA1 and CA3 neuronal layer. SK3 overexpression resulted in cognitive loss as determined by the object recognition test. Electrophysiological examination of hippocampal slices revealed that SK3 channel overexpression induced deficiency of long-term potentiation in hippocampal microcircuits. In association with these results, there were changes at the mRNA levels of some genes involved in Alzheimer's disease and/or linked to schizophrenia, epilepsy, and autism. Taken together, these features suggest that augmenting the function of SK3 ion channel in mice may present a unique opportunity to investigate the neural basis of central nervous system dysfunctions associated with schizophrenia, Alzheimer's disease, or other neuropsychiatric/neurodegenerative disorders in this model system. As a more detailed understanding of the role of the SK3 channel in brain disorders is limited by the lack of specific SK3 antagonists and agonists, the results observed in this study are of significant interest; they suggest a new approach for the development of neuroprotective strategies in neuropsychiatric/neurodegenerative diseases with SK3 representing a potential drug target. PMID- 26803495 TI - Persistent mitoKATP Activation Is Involved in the Isoflurane-induced Cytotoxicity. AB - Isoflurane exposure induces apoptosis in cultured cells and in the developing brain, while the underlying mechanism remains largely unclarified. This study was designed to determine whether the disruption of mitoKATP-mediated ATP balance was involved in the cytotoxicity of isoflurane. Human neuroglioma cells U251 and 7 day-old mice were treated with isoflurane. A specific mitoKATP antagonist 5-HD was used, and the cellular ATP levels, NAD+/NADH ratios, and mitochondrial transmembrane potential (DeltaPsim) were measured. Our data showed that the blockage of mitoKATP by 5-HD mitigated the isoflurane-induced DeltaPsim disruption, reactive oxygen species (ROS) accumulation, and apoptosis in U251 cells. Moreover, we found that the toxic effect of isoflurane was not observed in the first 2-h exposure; instead, the cellular ATP levels and NAD+/NADH ratios were markedly increased. The reduction of ATP levels and NAD+/NADH ratios was only detected after this initial phase. This dynamical effect of isoflurane was blocked by 5-HD. In contrast, a ROS scavenger NAC sustained the isoflurane induced ATP elevation. Similar results were observed in animal studies. And again, 5-HD attenuated isoflurane-induced cognitive disorders in the Intellicage test, a system that assesses place learning behavior in a social environment. Our study uncovered a potential mechanism underlying isoflurane's toxicity with a therapeutic future. PMID- 26803496 TI - Impacts of CD33 Genetic Variations on the Atrophy Rates of Hippocampus and Parahippocampal Gyrus in Normal Aging and Mild Cognitive Impairment. AB - The cluster of differentiation 33 (CD33) has been proved as a susceptibility locus associated with late-onset Alzheimer's disease (LOAD) based on recent genetic studies. Numerous studies have shown that multiple neuroimaging measures are potent predictors of AD risk and progression, and these measures are also affected by genetic variations in AD. Figuring out the association between CD33 genetic variations and AD-related brain atrophy may shed light on the underlying mechanisms of CD33-related AD pathogenesis. Thus, we investigated the influence of CD33 genotypes on AD-related brain atrophy to clarify the possible means by which CD33 impacts AD. A total of 48 individuals with probable AD, 483 mild cognitive impairment, and 281 cognitively normal controls were recruited from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. We investigated the influence of CD33 SNPs on hippocampal volume, parahippocampal gyrus volume, posterior cingulate volume, middle temporal volume, hippocampus CA1 subregion volume, and entorhinal cortex thickness. We found that brain regions significantly affected by CD33 genetic variations were restricted to hippocampal and parahippocampal gyrus in hybrid population, which were further validated in subpopulation (MCI and NC) analysis. These findings reaffirm the importance of the hippocampal and parahippocampal gyrus in AD pathogenesis, and present evidences for the CD33 variations influence on the atrophy of specific AD-related brain structures. Our findings raise the possibility that CD33 polymorphisms contribute to the AD risk by altering the neuronal degeneration of hippocampal and parahippocampal gyrus. PMID- 26803497 TI - Directed Differentiation of Dopamine-Secreting Cells from Nurr1/GPX1 Expressing Murine Embryonic Stem Cells Cultured on Matrigel-Coated PCL Scaffolds. AB - Parkinson's disease (PD) is a progressive neurological disorder characterized by a large number of motor and non-motor features and is known as the second most common neurodegenerative disorder after Alzheimer's disease. The hallmark pathology of PD is the damage and death of dopamine-producing neurons in the substantia-nigra of midbrain. Intrastriatal transplants of fetal mesencephalon derived DAergic neurons have provided proof-of-principle for the cell replacement strategy and have demonstrated reinnervation of the denervated striatum. However, ethical, technical, and practical limitations of deploying fetal DAergic neurons as the source for cell therapy in PD have ceased the spread of this procedure into clinical practice. Embryonic stem (ES) cells have emerged as a therapeutic alternative that can proliferate extensively and generate dopamine-producing neurons. To this extent and to surmount the obstacles related to embryonic neural cells, many investigations have focused on using pluripotent stem cells for the derivation of DAergic neurons. In the present study, a mouse embryonic stem (mES) R1 cell line was generated which could stably co-express Nurr1 (an essential transcription factor in DAergic neuron development) and GPX-1 (a neuroprotective enzyme against oxidative stress). The Nurr1/GPX-1-expressing ES cells (Nurr1/GPX 1-ES) were differentiated into DAergic-like cells via a three-dimensional culture environment consisting of Poly-epsilon-Caprolactone (PCL) nanofibrous scaffolds embedded by Matrigel (Mtg) in the presence of specific signaling molecules. DAergic neuron-specific genes were highly expressed in ES-derived DAergic neurons cultured and differentiated on PCL/Mtg scaffolds. Reverse-phase HPLC confirmed that the Nurr1/GPX-1-ES-cells differentiated on PCL/Mtg electrospun scaffolds could efficiently and exclusively secrete dopamine in response to stimulus. In conclusion, our results demonstrated that PCL/Matrigel nanofibrous scaffolds could efficiently support and promote the generation of functional DAergic-like cells from Nurr1/GPX-1-ES cells. The results of this study may have an impact on future tissue engineering for cell therapy of PD. PMID- 26803498 TI - Influence of microvascular dysfunction on regional myocardial deformation post acute myocardial infarction: insights from a novel angiographic index for assessing myocardial tissue-level reperfusion. AB - To investigate the impact of microvascular dysfunction assessed by angiography on myocardial deformation assessed by two-dimensional speckle-tracking echocardiography in ST-segment elevation myocardial infarction (STEMI). A total of 121 STEMI patients who received primary percutaneous coronary intervention were included. Thrombolysis in myocardial infarction, Myocardial Perfusion Frame Count (TMPFC), a novel angiographic method to assess myocardial perfusion, was used to evaluate microvascular dysfunction. Two-dimensional speckle-tracking echocardiography was performed at 3-7 days after reperfusion. The infarction related regional longitudinal (RLS) strains as well as circumferential (RCS) and radial (RRS) ones, along with global longitudinal, circumferential (GCS), and radial (GRS) strains were measured. Patients with microvascular dysfunction had decreased peak amplitude of RLS (p = 0.012), RCS (p < 0.001), RRS (p = 0.012) at the regional level and decreased peak amplitude of GCS (p = 0.005), GRS (p = 0.012) at the global level. The RCS to RLS and RCS to RRS ratios were significantly different between patients without than with microvascular dysfunction (1.28 +/- 0.31 vs. 1.07 +/- 0.47, p = 0.027 and 0.69 +/- 0.33 vs. 0.56 +/- 0.28, p = 0.047). Receiver operator characteristics curves identified a cutoff value of 94 frames for TMPFC to differentiate between normal and abnormal wall motion score index in the sub-acute phase of STEMI (AUC = 0.72; p < 0.001). In the sub-acute phase of STEMI, the presence of microvascular dysfunction in infarcted tissue relates to reduced global and regional myocardial deformation. RCS alterations were more significant than RLS and RRS between patients with than without microvascular dysfunction. TMPFC was useful to predict left ventricular systolic dysfunction in the sub-acute phase of STEMI. PMID- 26803499 TI - Self-administration of the anandamide transport inhibitor AM404 by squirrel monkeys. AB - RATIONALE: N-(4-hydroxyphenyl)-arachidonamide (AM404) is an anandamide transport inhibitor shown to reduce rewarding and relapse-inducing effects of nicotine in several animal models of tobacco dependence. However, the reinforcing/rewarding effects of AM404 are not clear. OBJECTIVES: We investigated whether AM404 maintains self-administration behavior or reinstates extinguished drug seeking in squirrel monkeys. METHODS AND RESULTS: In monkeys with a history of anandamide or cocaine self-administration, we substituted injections of AM404 (1-100 MUg/kg/injection). Using a 10-response, fixed-ratio schedule, self-administration behavior was maintained by AM404. Dose-response curves had inverted U shapes, with peak response rates occurring at a dose of 10 MUg/kg/injection. In anandamide-experienced monkeys, we also demonstrated self-administration of another anandamide transport inhibitor VDM11. In addition to supporting self administration, priming injections of AM404 (0.03-0.3 mg/kg) reinstated drug seeking behavior previously reinforced by cannabinoids (?(9)-tetrahydrocannabinol (THC) or anandamide) or cocaine. Both AM404 self-administration behavior and reinstatement of drug seeking by AM404 were reduced by treatment with the cannabinoid CB1 receptor antagonist/inverse agonist rimonabant (0.3 mg/kg). Moreover, the reinforcing effects of AM404 were potentiated by the treatment with the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3 mg/kg) suggesting a major role of anandamide in these effects. Finally, AM404 (0.3 mg/kg) potentiated the reinforcing effects of anandamide but not those of cocaine. CONCLUSIONS: In non-human primates, AM404 effectively reinforced self-administration behavior and induced reinstatement of drug-seeking behavior in abstinent monkeys. These effects appeared to be mediated by cannabinoid CB1 receptors. Therefore, compounds that promote actions of endocannabinoids throughout the brain by inhibiting their membrane transport may have a potential for abuse. PMID- 26803500 TI - Role of neuro-immunological factors in the pathophysiology of mood disorders. AB - Mood disorders, despite the widespread availability of monoamine-based antidepressant treatments, are associated with persistently high rates of disability, together with elevated rates of mortality due to suicide, cardiovascular disease, and other causes. The development of more effective treatments has been hindered by the lack of knowledge about the etiology and pathogenesis of mood disorders. An emerging area of science that promises novel pathways to antidepressant and mood stabilizing therapies surrounds evidence that immune cells and their signaling play a major role in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). Here, we review evidence that the release of neuroactive cytokines, particularly interleukins such as IL-1beta, IL-6, and TNF-alpha, is altered in these disorders and discuss mechanisms such as the ATP-gated ion channel P2X7, through which cytokine signaling can influence neuro-glial interactions. Brain P2X7, an emerging target and antagonism of P2X7 holds promise as a novel mechanism for targeting treatment resistant depression. We further discuss the role of microglia and astroglia in central neuroinflammation and their interaction with the peripheral immune system We present extant clinical evidence that bolsters the role of neuroinflammation and neuroactive cytokines in mood disorders. To that end, the role of clinical imaging by probing neuroinflammatory markers is also discussed briefly. Finally, we present data using preclinical neuroinflammation models that produce depression-like behaviors in experimental animals to identify neuroinflammatory mechanisms which may aid in novel neuroimmune target identification for the development of exciting pharmacological interventions in mood disorders. PMID- 26803501 TI - Molecular interactions of the gamma-clade homeodomain-leucine zipper class I transcription factors during the wheat response to water deficit. AB - The gamma-clade of class I homeodomain-leucine zipper (HD-Zip I) transcription factors (TFs) constitute members which play a role in adapting plant growth to conditions of water deficit. Given the importance of wheat (Triticum aestivum L.) as a global food crop and the impact of water deficit upon grain yield, we focused on functional aspects of wheat drought responsive HD-Zip I TFs. While the wheat gamma-clade HD-Zip I TFs share significant sequence similarities with homologous genes from other plants, the clade-specific features in transcriptional response to abiotic stress were detected. We demonstrate that wheat TaHDZipI-3, TaHDZipI-4, and TaHDZipI-5 genes respond differentially to a variety of abiotic stresses, and that proteins encoded by these genes exhibit pronounced differences in oligomerisation, strength of DNA binding, and trans activation of an artificial promoter. Three-dimensional molecular modelling of the protein-DNA interface was conducted to address the ambiguity at the central nucleotide in the pseudo-palindromic cis-element CAATNATTG that is recognised by all three HD-Zip I proteins. The co-expression of these genes in the same plant tissues together with the ability of HD-Zip I TFs of the gamma-clade to hetero dimerise suggests a role in the regulatory mechanisms of HD-Zip I dependent transcription. Our findings highlight the complexity of TF networks involved in plant responses to water deficit. A better understanding of the molecular complexity at the protein level during crop responses to drought will enable adoption of efficient strategies for production of cereal plants with enhanced drought tolerance. PMID- 26803503 TI - Production of biorenewable styrene: utilization of biomass-derived sugars and insights into toxicity. AB - Fermentative production of styrene from glucose has been previously demonstrated in Escherichia coli. Here, we demonstrate the production of styrene from the sugars derived from lignocellulosic biomass depolymerized by fast pyrolysis. A previously engineered styrene-producing strain was further engineered for utilization of the anhydrosugar levoglucosan via expression of levoglucosan kinase. The resulting strain produced 240 +/- 3 mg L(-1) styrene from pure levoglucosan, similar to the 251 +/- 3 mg L(-1) produced from glucose. When provided at a concentration of 5 g L(-1), pyrolytic sugars supported styrene production at titers similar to those from pure sugars, demonstrating the feasibility of producing this important industrial chemical from biomass-derived sugars. However, the toxicity of contaminant compounds in the biomass-derived sugars and styrene itself limit further gains in production. Styrene toxicity is generally believed to be due to membrane damage. Contrary to this prevailing wisdom, our quantitative assessment during challenge with up to 200 mg L(-1) of exogenously provided styrene showed little change in membrane integrity; membrane disruption was observed only during styrene production. Membrane fluidity was also quantified during styrene production, but no changes were observed relative to the non-producing control strain. This observation that styrene production is much more damaging to the membrane integrity than challenge with exogenously supplied styrene provides insight into the mechanism of styrene toxicity and emphasizes the importance of verifying proposed toxicity mechanisms during production instead of relying upon results obtained during exogenous challenge. PMID- 26803502 TI - Constitutive expression of CaPLA1 conferred enhanced growth and grain yield in transgenic rice plants. AB - Phospholipids are not only important components of cell membranes, but participate in diverse processes in higher plants. In this study, we generated Capsicum annuum phospholipiase A1 (CaPLA1) overexpressing transgenic rice (Oryza sativa L.) plants under the control of the maize ubiquitin promoter. The T4 CaPLA1-overexpressing rice plants (Ubi:CaPLA1) had a higher root:shoot mass ratio than the wild-type plants in the vegetative stage. Leaf epidermal cells from transgenic plants had more cells than wild-type plants. Genes that code for cyclin and lipid metabolic enzymes were up-regulated in the transgenic lines. When grown under typical paddy field conditions, the transgenic plants produced more tillers, longer panicles and more branches per panicle than the wild-type plants, all of which resulted in greater grain yield. Microarray analysis suggests that gene expressions that are related with cell proliferation, lipid metabolism, and redox state were widely altered in CaPLA1-overexpressing transgenic rice plants. Ubi:CaPLA1 plants had a reduced membrane peroxidation state, as determined by malondialdehyde and conjugated diene levels and higher peroxidase activity than wild-type rice plants. Furthermore, three isoprenoid synthetic genes encoding terpenoid synthase, hydroxysteroid dehydrogenase and 3 hydroxy-3-methyl-glutaryl-CoA reductase were up-regulated in CaPLA1 overexpressing plants. We suggest that constitutive expression of CaPLA1 conferred increased grain yield with enhanced growth in transgenic rice plants by alteration of gene activities related with cell proliferation, lipid metabolism, membrane peroxidation state and isoprenoid biosynthesis. PMID- 26803504 TI - A new approach for improving epothilone B yield in Sorangium cellulosum by the introduction of vgb epoF genes. AB - Epothilone B has drawn great attention due to its much stronger anticancer activity and weaker side effects compared with taxol. The relative low yield of epothilone B limited its application. In this study, we report the successful introduction of the vgb gene and the epoF gene into Sorangium cellulosum So ce M4 by electroporation for the first time, which was demonstrated by Southern blot analysis. Results of qRT-PCR, SDS-PAGE and western blot analysis confirmed the transcription and expression of the vgb and epoF genes. LC-MS results showed that the epothilones B, A yields were improved and epothilones D, C yields were decreased. The yields of epothilone B were improved by 57.9 +/- 0.3, 62.7 +/- 0.8 and 122.4 +/- 0.7 % through the introduction of vgb gene, epoF gene and both genes into strain So ce M4, respectively. Our study provides a new approach for improving epothilone B yield in S. cellulosum. PMID- 26803505 TI - A xylanase from Streptomyces sp. FA1: heterologous expression, characterization, and its application in Chinese steamed bread. AB - Xylanases (EC 3.2.1.8) are hydrolytic enzymes that have found widespread application in the food, feed, and paper-pulp industries. Streptomyces sp. FA1 xynA was expressed as a secreted protein in Pichia pastoris, and the xylanase was applied to the production of Chinese steamed bread for the first time. The optimal pH and the optimal temperature of XynA were 5.5 and 60 degrees C, respectively. Using beechwood as substrate, the K m and V max were 2.408 mg mL( 1) and 299.3 umol min(-1) mg(-1), respectively. Under optimal conditions, a 3.6-L bioreactor produced 1374 U mL(-1) of XynA activity at a protein concentration of 6.3 g L(-1) after 132 h of fermentation. Use of recombinant XynA led to a greater increase in the specific volume of the CSB than could be achieved using commercial xylanase under optimal conditions. This study provides the basis for the application of the enzyme in the baking industry. PMID- 26803506 TI - Head CT: Image quality improvement of posterior fossa and radiation dose reduction with ASiR - comparative studies of CT head examinations. AB - OBJECTIVES: To evaluate head CT protocol developed to improve visibility of the brainstem and cerebellum, lower bone-related artefacts in the posterior fossa and maintain patient radioprotection. METHODS: A paired comparison of head CT performed without Adaptive Statistical Iterative Reconstruction (ASiR) and a clinically indicated follow-up with 40 % ASiR was acquired in one group of 55 patients. Patients were scanned in the axial mode with different scanner settings for the brain and the posterior fossa. Objective image quality analysis was performed with signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Subjective image quality analysis was based on brain structure visibility and evaluation of the artefacts. RESULTS: We achieved 19 % reduction of total DLP and significantly better image quality of posterior fossa structures. SNR for white and grey matter in the cerebellum were 34 % to 36 % higher, respectively, CNR was improved by 142 % and subjective analyses were better for images with ASiR. CONCLUSIONS: When imaging parameters are set independently for the brain and the posterior fossa imaging, ASiR has a great potential to improve CT performance: image quality of the brainstem and cerebellum is improved, and radiation dose for the brain as well as total radiation dose are reduced. KEY POINTS: *With ASiR it is possible to lower radiation dose or improve image quality *Sequentional imaging allows setting scan parameters for brain and posterior-fossa independently *We improved visibility of brainstem structures and decreased radiation dose *Total radiation dose (DLP) was decreased by 19. PMID- 26803507 TI - Reconstruction of paediatric organ doses from axial CT scans performed in the 1990s - range of doses as input to uncertainty estimates. AB - OBJECTIVE: To assess the range of doses in paediatric CT scans conducted in the 1990s in Norway as input to an international epidemiology study: the EPI-CT study, http://epi-ct.iarc.fr/ . METHODS: National Cancer Institute dosimetry system for Computed Tomography (NCICT) program based on pre-calculated organ dose conversion coefficients was used to convert CT Dose Index to organ doses in paediatric CT in the 1990s. Protocols reported from local hospitals in a previous Norwegian CT survey were used as input, presuming these were used without optimization for paediatric patients. RESULTS: Large variations in doses between different scanner models and local scan parameter settings are demonstrated. Small children will receive a factor of 2-3 times higher doses compared with adults if the protocols are not optimized for them. For common CT examinations, the doses to the active bone marrow, breast tissue and brain may have exceeded 30 mGy, 60 mGy and 100 mGy respectively, for the youngest children in the 1990s. CONCLUSIONS: The doses children received from non-optimised CT examinations during the 1990s are of such magnitude that they may provide statistically significant effects in the EPI-CT study, but probably do not reflect current practice. KEY POINTS: * Some organ doses from paediatric CT in the 1990s may have exceeded 100 mGy. * Small children may have received doses 2-3 times higher compared with adults. * Different scanner models varied by a factor of 2-3 in dose to patients. * Different local scan parameter settings gave dose variations of a factor 2-3. * Modern CTs and age-adjusted protocols will give much lower paediatric doses. PMID- 26803508 TI - Erratum to: Revisiting the Mesosome as a Novel Site of Hydrogen Peroxide Accumulation in Escherichia coli. PMID- 26803509 TI - Biomarkers of vascular dysfunction and cognitive decline in patients with Alzheimer's disease: no evidence for association in elderly subjects. AB - BACKGROUND: Several studies have suggested that vascular dysfunction plays an important role in Alzheimer's disease. AIMS: We hypothesized that significant differences might be observed in the levels of blood endothelial biomarkers across elderly population of subjects with dementia. METHODS: We analyzed, in a prospective monocentric study, three different endothelial biomarkers, endothelial microparticles (EMPs), endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) in 132 older patients who underwent a full evaluation of a memory complaint. RESULTS: There was no difference in specific EMP, EPC or CEC levels between demented or non-demented patients, nor considering cognitive decline. DISCUSSION: Blood endothelial biomarkers may be too sensitive and it is likely that the multimorbidity observed in our patients may lead to opposite and confounding effects on endothelial biomarkers levels. CONCLUSION: Unlike younger AD patients, our results suggest that endothelial biomarkers are not valuable for the diagnosis of dementia in elderly patients. PMID- 26803510 TI - Nordic walking in the second half of life. AB - OBJECTIVES: The objective of this article is to review the literature regarding the effectiveness and safety of Nordic walking (NW) in therapeutic rehabilitation in patients of an advanced age. METHODS: Randomized studies comparing NW with different patterns of long-lasting physical rehabilitation in older adults (average age 65 years) were selected for the review. Studies were identified through a Medline database search covering the last 21 years. RESULTS: Seventy four studies on this subject were identified, 37 of them fulfilled the required criteria and 27 of these were analyzed in this review. DISCUSSION: Nordic walking provides a safe and effective way to enhance physical activity in the elderly. It could also serve as a method of rehabilitation that improves fitness, the performance and the exercise capacity of aged persons with diseases associated with an advanced age: cardiovascular diseases due to atherosclerosis; metabolic syndrome without diabetes; early stage Parkinson's disease; chronic obstructive pulmonary disease and lowering depression in women with Sjogren's Syndrome. PMID- 26803511 TI - Cardiac Rehabilitation in Patients with Established Atherosclerotic Vascular Disease: New Directions in the Era of Value-Based Healthcare. AB - Exercise-based cardiac rehabilitation (CR) is associated with significant improvements in coronary disease outcomes, but has been underutilized. However, new developments within the field, some spurred by healthcare reform and the transition to more accountable and coordinated care, offer hope for closing the large CR treatment gap. This review presents new CR-related research, policy, and analyses, and discusses how evolving eligibility criteria, referral processes, performance measures, care models, and delivery and payment options could increase CR utilization over the next decade and enable this life-saving secondary prevention intervention to thrive in the era of value-based health care. PMID- 26803512 TI - The chemical coding of 5-hydroxytryptamine containing enteroendocrine cells in the mouse gastrointestinal tract. AB - The majority of 5-HT (serotonin) in the body is contained in enteroendocrine cells of the gastrointestinal mucosa. From the time of their discovery over 80 years ago, the 5-HT-containing cells have been regarded as a class of cell that is distinct from enteroendocrine cells that contain peptide hormones. However, recent studies have cast doubt on the concept of there being distinct classes of enteroendocrine cells, each containing a single hormone or occasionally more than one hormone. Instead, data are rapidly accumulating that there are complex patterns of colocalisation of hormones that identify multiple subclasses of enteroendocrine cells. In the present work, multiple labelling immunohistochemistry is used to investigate patterns of colocalisation of 5-HT with enteric peptide hormones. Over 95 % of 5-HT cells in the duodenum also contained cholecystokinin and about 40 % of them also contained secretin. In the jejunum, about 75 % of 5-HT cells contained cholecystokinin but not secretin and 25 % contained 5-HT plus both cholecystokinin and secretin. Small proportions of 5-HT cells contained gastrin or somatostatin in the stomach, PYY or GLP-1 in the small intestine and GLP-1 or somatostatin in the large intestine. Rare or very rare 5-HT cells contained ghrelin (stomach), neurotensin (small and large intestines), somatostatin (small intestine) and PYY (in the large intestine). It is concluded that 5-HT-containing enteroendocrine cells are heterogeneous in their chemical coding and by implication in their functions. PMID- 26803513 TI - Critical role for the long non-coding RNA AFAP1-AS1 in the proliferation and metastasis of hepatocellular carcinoma. AB - Increasing evidence has indicated that dysregulation of long non-coding RNAs (lncRNAs) can contribute to the progression and metastasis of human cancer, including HCC. Previous studies have shown that the lncRNA AFAP1-AS1 plays a critical role in cancer. However, the roles of AFAP1-AS1 in HCC remain to be determined. In the present study, AFAP1-AS1 was found to be increased in HCC tissues, and high AFAP1-AS1 expression was associated with tumor size, TNM stage, vascular invasion, and poor prognosis. Silencing of AFAP1-AS1 significantly reduced cell proliferation, clonal growth, cell migration, and invasion and increased apoptosis in vitro. Furthermore, AFAP1-AS1 silencing markedly reduced tumor growth in a murine allograft model in vivo. The results suggested that AFAP1-AS1 is important in HCC development and serves as a therapeutic target of HCC. PMID- 26803514 TI - Iron chelator-induced apoptosis via the ER stress pathway in gastric cancer cells. AB - Many reports have shown the anticancer effects of iron deficient on cancer cells, but the effects of iron-chelators on gastric cancer have not been clearly elucidated. Recently, we reported that iron chelators induced an antiproliferative effect in human malignant lymphoma and myeloid leukemia cells. In the present study, we investigated the antitumor activity of these two iron chelating agents, deferoxamine (DFO) and deferasirox (DFX), with gastric cancer cell lines, and their apoptosis-inducing effects as the potential mechanism. We found that iron chelators displayed significant antiproliferative activity in human gastric cancer cell lines, which may be attributed to their induction of G1 phase arrest and apoptosis. We also found that iron chelators induced reactive oxygen species (ROS) production, resulting in the activation of both c-Jun N terminal kinase (JNK) and endoplasmic reticulum (ER) stress apoptotic pathways in gastric cancer cells. Taken together, our data suggest that iron chelators induced apoptosis in gastric cancer, involving ROS formation ER stress and JNK activation. PMID- 26803515 TI - Long noncoding RNA H19 contributes to gallbladder cancer cell proliferation by modulated miR-194-5p targeting AKT2. AB - Gallbladder cancer (GBC) is a highly malignant cancer with poor prognosis. Although long noncoding RNA (lncRNA) H19 has been reported to play vital role in many human cancers, whether it is involved in GBC proliferation is still unknown. This study was designed to explore the effect of H19 in GBC cell proliferation. The expression of H19 and AKT2 were significantly elevated in GBC tissues, and the level of miR-194-5p is markedly decreased. Moreover, the RNA levels of H19 and AKT2 were positively correlated, and H19 elevation was significantly associated with tumor size. Cell proliferation decreased significantly after knockdown of H19 in GBC-SD and NOZ cells and after knockdown of AKT2 in NOZ cells. Results from cell cycle studies indicated that the S phase were significantly decreased after knockdown of H19 in NOZ cells but significantly elevated after overexpression of H19 in GBC-SD cells. Furthermore, knockdown of H19 upregulated miR-194-5p levels, yet significantly decreased miR-194-5p targeting AKT2 gene expression in NOZ cells. Inhibitor against miR-194-5p reversed these effects. In addition, overexpression of H19 in GBC-SD cells downregulated miR-194-5p and markedly increased AKT2 expression, and miR-194-5p mimic reversed these effects. Eventually, GBC cells were arrested in G0/G1-phase after H19 knockdown, inhibition of miR-194-5p markedly promoted cells into S phase and co-transfection of siH19, and miR-194-5p inhibitor exerted mutually counter-regulated effects on cell cycle. These results suggested that H19/miR-194 5p/AKT2 axis regulatory network might modulate cell proliferation in GBC. PMID- 26803516 TI - ING3 is associated with increased cell invasion and lethal outcome in ERG negative prostate cancer patients. AB - The inhibitor of growth family member 3 (ING3) is a member of the ING tumor suppressor family. Although its expression has been reported in various types of cancers, the role of ING3 and its prognostic value in prostate cancer (PCa) has not been investigated. ING3 expression and prognostic value was assessed in a cohort of PCa patients (n = 312) treated with transurethral resection of prostate using immumoflourescent automated quantitative analysis (AQUA) system. In vitro studies were carried out in conjunction to investigate its expression in various PCa cell lines. ING3 knockdown was also carried out in DU145 cell lines to assess for any changes in invasion and migration. ING3 expression was highest in benign prostate tissues (mean 3.2 +/- 0.54) compared to PCa (mean 2.5 +/- 0.26) (p = 0.437), advanced prostate cancer (AdvPCa) (mean 1.5 +/- 0.32) (p = 0.004), and castration-resistant prostate cancer (CRPC) (mean 2.28 +/- 0.32) (p = 0.285). ING3 expression was inversely correlated to Gleason score (p = 0.039) and ETS related gene (ERG) expression (p = 0.019). Higher ING3 expression was marginally associated with lethal disease (p = 0.052), and this was more pronounced in patients with ERG-negative status (p = 0.018). Inhibition of ING3 in DU145 PCa cells using small interfering RNA (siRNA) was associated with decreased cell invasion (p = 0.0016) and cell migration compared to control cells. ING3 is significantly associated with PCa disease progression and cancer-specific mortality. To our knowledge, this is the first report suggesting an oncogenic function of ING3, previously well known as a tumor suppressor protein. Further studies should investigate potential-related pathways in association to ING3. PMID- 26803517 TI - Relationship between five GWAS-identified single nucleotide polymorphisms and female breast cancer in the Chinese Han population. AB - With the development of genome-wide association study (GWAS), an increasing number of genetic variables have been confirmed to be associated with breast cancer. Furthermore, an increasing number of studies from Asian populations are becoming available. Few GWAS loci have been replicated in the Chinese Han population. In a case-control study of breast cancer in the Henan Tumor Hospital (253 cases/339 controls), we evaluated five SNPs from GWAS of populations of European or Asian ancestry. In order to evaluate the contribution of genetic factors to population differences in breast cancer subtypes, all cases are defined by estrogen (ER), progesterone (PR) receptor, Human epidermal growth factor receptor - 2 (HER2), and Ki67 status. Different genotypes of rs3803662 (TOX3)/ (TNRC9)) in the case group and the control group are statistically significant (P = 0.044), but the ones of rs10069690 (TERT), rs2046210 (6q25.1), rs2981582 (EGFR2), and rs889312 (MAP3K1) have no significant statistical differences with breast cancer (P = 0.772, 0.308, 0.376, 0.468). The allelic frequencies of rs3803662 between the case group and the control group differ in recessive genetic models (odds ratio (OR) = 2.04, 95 % confidence interval (CI) 1.14-3.66) and in con-dominant inheritance models (OR = 2.17, 95 % CI 1.18-4.00). Compared with AA and GA, GG increased the risk of breast cancer (P = 0.017, 0.013). The genotype of rs2046210 (6q25.1), rs2981582 (EGFR2), rs889312 (MAP3K1), and rs3803662 (TOX3/TNRC9) has no statistical differences in different subtypes of breast cancer. Five common breast cancer susceptibility loci from GWAS are not strongly associated with breast cancer risk among the Han Chinese of the Henan province; only rs3803662 (TOX3/TNRC9) is confirmed to increase the risk of breast cancer. The different genotypes of five loci distribute equally in different subtypes of breast cancer. PMID- 26803518 TI - Inhibitor of growth-4 is a potential target for cancer therapy. AB - The inhibitor of growth-4 (ING-4) belongs to the inhibitor of growth (ING) family that is a type II tumor suppressor gene including five members (ING1-5). As a tumor suppressor, ING4 inhibits tumor growth, invasion, and metastasis by multiple signaling pathways. In addition to that, ING4 can facilitate cancer cell sensitivity to chemotherapy and radiotherapy. Although ING4 loss is observed for many types of cancers, increasing evidences show that ING4 can be used for gene therapy. In this review, the recent progress of ING4 regulating tumorigenesis is discussed. PMID- 26803519 TI - Carboxypeptidase E is a prediction marker for tumor recurrence in early-stage hepatocellular carcinoma. AB - Tumor recurrence and metastasis are the major causes of death for hepatocellular carcinoma (HCC) patients who are able to receive curative resection. Identifying the predicting biomarkers for tumor recurrence would improve their survival. RNA extracted from fresh frozen tumors and adjacent non-tumor liver tissues of 120 HCC patients were obtained from Taiwan Liver Cancer Network (TLCN) in year 2010 for determination of the carboxypeptidase E (CPE) expression level (including its splicing mutant CPE-DeltaN) in the tumor tissue (T) and paired non-tumor liver tissue (N) by real-time quantitative polymerase chain reaction. All patients were male, had chronic hepatitis B virus infection, were in the early pathology stage, and received curative resection. The T/N ratio of the CPE expression level was correlated with the updated survival data from TLCN in 2015. The CPE expression level in the 120 HCC patients was divided into three groups according to the T/N ratio: <1, >=1 and <=2, and >2, respectively. By multivariate analyses, the recurrence-free survival (RFS) was only significantly associated with the pathology stage and the CPE expression level. For overall survival (OS), only the CPE expression level was the significant prognostic factor. The CPE expression level was also significantly correlated with the tumor recurrence for both stage I (p = 0.0106) and stage II patients (p = 0.0006). The CPE mRNA expression level in HCC can be a useful biomarker for predicting tumor recurrence in HCC patients who are in the early pathology stage and able to receive curative resection. PMID- 26803520 TI - The role of the Annexin-A1/FPR2 system in the regulation of mast cell degranulation provoked by compound 48/80 and in the inhibitory action of nedocromil. AB - 1.We investigated the role of Annexin (ANX)-A1 and its receptor, ALX/FPR2, in the regulation of mast cell degranulation produced by compound 48/80. 2.Both human cord-blood derived mast cells (CBDMCs) and murine bone marrow derived mast cells (BMDMCs) release phosphorylated ANX-A1 during treatment with glucocorticoids or the mast cell 'stabilising' drugs ketotifen and nedocromil. 3.Compound 48/80 also stimulated ANX-A1 phosphorylation and release and this was also potentiated by nedocromil. Anti-ANX-A1 neutralising monoclonal antibodies (Mabs) enhanced the release of pro-inflammatory mediators in response to compound 48/80. 4.Nedocromil and ketotifen potently inhibited the release of histamine, PGD2, tryptase and beta-hexosaminidase from mast cells challenged with compound 48/80. Anti-ANX-A1 neutralising Mabs prevented the inhibitory effect of these drugs. 5.BMDMCs derived from Anx-A1-/- mice were insensitive to the inhibitory effects of nedocromil or ketotifen but cells retained their sensitivity to the inhibitory action of hu-r-ANX-A1. 6.The fpr2/3 antagonist WRW4 blocked the action of nedocromil on PGD2, but not histamine, release. BMDMCs derived from fpr2/3-/- mice were insensitive to the inhibitory effects of nedocromil on PGD2, but not histamine release. 7.Compound 48/80 stimulated both p38 and JNK phosphorylation in CBDMCs and this was inhibited by nedocromil. Inhibition of p38 phosphorylation was ANX-A1 dependent. 8.We conclude that ANX-A1 is an important regulator of mast cell reactivity to compound 48/80 exerting a negative feedback effect through a mechanism that depends at least partly on the FPR receptor. PMID- 26803521 TI - TLR4 signaling mediates AP-1 activation in an MPTP-induced mouse model of Parkinson's disease. AB - OBJECTIVE: To evaluate the effects of Toll-like receptor 4 (TLR4) signaling on the activation of the transcription factor activator protein-1 (AP-1) in a 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease (PD). METHODS: The following groups were evaluated: normal saline (NS)-treated WT mice, NS-treated TLR4-knockout (KO) mice, MPTP-treated WT mice, and MPTP-treated TLR4-KO mice. After establishing the mouse model, behavioral changes were evaluated. AP-1 expression was detected by RT-PCR, Western blotting, immunohistochemistry and immunofluorescence staining. RESULTS: Compared to MPTP-treated WT mice, significantly reduced dyskinesia was observed in MPTP-treated TLR4-KO mice. AP-1 mRNA and protein levels were significantly up regulated in the substantia nigras (SNs) of MPTP-treated WT mice relative to NS treated mice (P<0.01); these levels were significantly reduced in MPTP-treated TLR4-KO mice relative to MPTP-treated WT mice (P<0.01). Immunohistochemical staining demonstrated that AP-1 was distributed throughout the SN in MPTP-treated mice, and immunofluorescence further showed that AP-1 was expressed in TH positive neuronal cells and GFAP-positive astrocytes. In addition, immunofluorescence revealed that AP-1 expression was lower in TH-positive neurons and GFAP-positive astrocytes in the SNs of MPTP-treated TLR4-KO mice relative to MPTP-treated WT mice. CONCLUSIONS: The TLR4 pathway may play an important role in regulating AP-1 activation. PMID- 26803522 TI - What are the progesterone-induced changes of the outcome and the serum markers of injury, oxidant activity and inflammation in diffuse axonal injury patients? AB - To permit appropriate targeted therapy, the present clinical study was aimed to investigate the effects of progesterone on the outcome and the serum markers of injury, oxidant activity and inflammation in diffuse axonal injury (DAI). Forty eight male DAI patients were divided into two groups (control and progesterone). Progesterone group received progesterone in dose of 1mg/kg per 12h for five days. The outcome was investigated using Extended Glasgow Outcome Scale (GOS-E) and functional independence measure (FIM). The markers of inflammation [interleukin 1beta (IL-1beta), IL-6, transforming growth factor-beta1 (TGF-beta1)], injury (brain protein of S-100B), and oxidant activity [malondialdehyde (MDA)] were evaluated in the serum of the patients. Higher GOS-E and FIM scores were observed in progesterone group at the six-month follow-up (P<0.05 and P<0.01, respectively). Meanwhile, a reduction in the serum levels of IL-1beta, MDA and S 100B was noticed in progesterone group 24h after injury (P<0.05, P<0.001 and P<0.05, respectively), and there was an increase in serum levels of IL-6 and TGF beta1 (P<0.01 and P<0.05, respectively). Also, lower levels of MDA and S-100B, and higher levels of TGF-beta1 were observed in progesterone group six days after injury (P<0.05). According to these findings, progesterone may improve the outcome in DAI patients probably through modulation in the levels of cytokines, and reduction in the injury and oxidant activity. PMID- 26803523 TI - Acanthoic acid inhibits LPS-induced inflammatory response by activating LXRalpha in human umbilical vein endothelial cells. AB - Acanthoic acid, a pimaradiene diterpene isolated from Acanthopanax koreanum, has been reported to have anti-inflammatory activities. However, the effect of acanthoic acid on vascular inflammation has not been investigated. The aim of this study was to investigate the anti-inflammatory effects of acanthoic acid on lipopolysaccharide (LPS)-induced inflammatory response in human umbilical vein endothelial cells (HUVECs). The production of cytokines TNF-alpha and IL-8 was detected by ELISA. The expression of VCAM-1, ICAM-1, E-selectin, NF-kappaB and LXRalpha were detected by Western blotting. Adhesion of monocytes to HUVECs was detected by monocytic cell adhesion assay. The results showed that acanthoic acid dose-dependently inhibited LPS-induced TNF-alpha and IL-8 production. Acanthoic acid also inhibited TNF-alpha-induced IL-8 and IL-6 production. LPS-induced endothelial cell adhesion molecules, VCAM-1 and ICAM-1 were also inhibited by acanthoic acid. Acanthoic acid inhibited LPS-induced NF-kappaB activation. Furthermore, acanthoic acid dose-dependently up-regulated the expression of LXRalpha. In addition, our results showed that the anti-inflammatory effect of acanthoic acid was attenuated by transfection with LXRalpha siRNA. In conclusion, the anti-inflammatory effect of acanthoic acid is due to its ability to activate LXRalpha. Acanthoic acid may be a therapeutic agent for inflammatory cardiovascular disease. PMID- 26803524 TI - Biological responses of wheat (Triticum aestivum) plants to the herbicide simetryne in soils. AB - The rotation of rice and wheat is widely used and highly endorsed, and simetryne (s-triazine herbicide) is one of the principal herbicides widely used in this rotation for weed and grass control. However, little is known regarding the mechanism of the ecological and physiological effects of simetryne on wheat crops. In this study, we performed a comprehensive investigation of crop response to simetryne to elucidate the accumulation and phytotoxicity of the herbicide in wheat crops. Wheat plants exposed to 0.8 to 8.0mgkg(-1) simetryne for 7 d exhibited suppressed growth and decreased chlorophyll content. With simetryne concentration in the soil varied from 0.8mgkg(-1) to 8.0mgkg(-1), simetryne was progressively accumulated by the wheat plants. The accumulation of simetryne in the wheat plants not only induced the over production of ROS and injured the membrane lipids but also stimulated the production of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), ascorbate peroxidase (APX), glutathione reductase (GR) and glutathione S-transferase (GST). A test of enzymatic activity and gene expression illustrated that the wheat plants were wise enough to motivate the antioxidant enzymes through both molecular and physiological mechanisms to alleviate the simetryne-induced stress. This study offers an illuminating insight into the effective adaptive response of the wheat plants to the simetryne stress. PMID- 26803525 TI - Effects of expiratory muscle strength training on oropharyngeal dysphagia in subacute stroke patients: a randomised controlled trial. AB - Expiratory muscle strength training (EMST) involves forcible blowing as a means of generating high expiratory pressure, against adjustable resistance. EMST has recently been introduced as a potential treatment for dysphagia. This study was performed to investigate the effects of EMST on the activity of suprahyoid muscles, aspiration and dietary stages in stroke patients with dysphagia. Twenty seven stroke patients with dysphagia were randomly divided into two groups. The experimental group performed EMST with a 70% threshold value of maximal expiratory pressure, using an EMST device, 5 days a week for 4 weeks. The placebo group trained with a sham device. The EMST regime involved 5 sets of 5 breaths through the EMST device for a total of 25 breaths per day. Activity in the suprahyoid muscle group was measured using surface electromyography (sEMG). Further, the penetration-aspiration scale (PAS) was used to assess the results of the videofluoroscopic swallowing study (VFSS). In addition, dietary stages were evaluated using the Functional Oral Intake Scale (FOIS). The experimental group exhibited improved suprahyoid muscle group activity and PAS results, when compared to the placebo group. Following intervention, statistical analysis indicated significant differences in measured suprahyoid muscle activity (P = 0.01), liquid PAS outcomes (P = 0.03) and FOIS results (P = 0.06), but not semisolid type PAS outcomes (P = 0.32), between the groups. This study confirms EMST as an effective treatment for the development of suprahyoid muscle activity in stroke patients with dysphagia. Additionally, improvements in aspiration and penetration outcomes were observed. PMID- 26803526 TI - Methods for assessment of trunk stabilization, a systematic review. AB - Trunk stabilization is achieved differently in patients with low back pain compared to healthy controls. Many methods exist to assess trunk stabilization but not all measure the contributions of intrinsic stiffness and reflexes simultaneously. This may pose a threat to the quality/validity of the study and might lead to misinterpretation of the results. The aim of this study was to provide a critical review of previously published methods for studying trunk stabilization in relation to low back pain (LBP). We primarily aimed to assess their construct validity to which end we defined a theoretical framework operationalized in a set of methodological criteria which would allow to identify the contributions of intrinsic stiffness and reflexes simultaneously. In addition, the clinimetric properties of the methods were evaluated. A total of 133 articles were included from which four main categories of methods were defined; upper limb (un)loading, moving platform, unloading and loading. Fifty of the 133 selected articles complied with all the criteria of the theoretical framework, but only four articles provided information about reliability and/or measurement error of methods to assess trunk stabilization with test-retest reliability ranging from poor (ICC 0) to moderate (ICC 0.72). When aiming to assess trunk stabilization with system identification, we propose a perturbation method where the trunk is studied in isolation, the perturbation is unpredictable, force controlled, directly applied to the upper body, completely known and results in small fluctuations around the working point. PMID- 26803527 TI - Acute stress influences the discrimination of complex scenes and complex faces in young healthy men. AB - The stress-induced release of glucocorticoids has been demonstrated to influence hippocampal functions via the modulation of specific receptors. At the behavioral level stress is known to influence hippocampus dependent long-term memory. In recent years, studies have consistently associated the hippocampus with the non mnemonic perception of scenes, while adjacent regions in the medial temporal lobe were associated with the perception of objects, and faces. So far it is not known whether and how stress influences non-mnemonic perceptual processes. In a behavioral study, fifty male participants were subjected either to the stressful socially evaluated cold-pressor test or to a non-stressful control procedure, before they completed a visual discrimination task, comprising scenes and faces. The complexity of the face and scene stimuli was manipulated in easy and difficult conditions. A significant three way interaction between stress, stimulus type and complexity was found. Stressed participants tended to commit more errors in the complex scenes condition. For complex faces a descriptive tendency in the opposite direction (fewer errors under stress) was observed. As a result the difference between the number of errors for scenes and errors for faces was significantly larger in the stress group. These results indicate that, beyond the effects of stress on long-term memory, stress influences the discrimination of spatial information, especially when the perception is characterized by a high complexity. PMID- 26803529 TI - Postpartum estrogen withdrawal impairs hippocampal neurogenesis and causes depression- and anxiety-like behaviors in mice. AB - Postpartum estrogen withdrawal is known to be a particularly vulnerable time for depressive symptoms. Ovariectomized adult mice (OVX-mice) treated with hormone simulated pregnancy (HSP mice) followed by a subsequent estradiol benzoate (EB) withdrawal (EW mice) exhibited depression- and anxiety-like behaviors, as assessed by forced swim, tail suspension and elevated plus-maze, while HSP mice, OVX mice or EB-treated OVX mice (OVX/EB mice) did not. The survival and neurite growth of newborn neurons in hippocampal dentate gyrus were examined on day 5 after EW. Compared with controls, the numbers of 28-day-old BrdU(+) and BrdU(+)/NeuN(+) cells were increased in HSP mice but significantly decreased in EW mice; the numbers of 10-day-old BrdU(+) cells were increased in HSP mice and OVX/EB mice; and the density of DCX(+) fibers was reduced in EW mice and OVX mice. The phosphorylation of hippocampal NMDA receptor (NMDAr) NR2B subunit or Src was increased in HSP mice but decreased in EW mice. NMDAr agonist NMDA prevented the loss of 28-day-old BrdU(+) cells and the depression- and anxiety like behaviors in EW mice. NR2B inhibitor Ro25-6981 or Src inhibitor dasatinib caused depression- and anxiety-like behaviors in HSP mice with the reduction of 28-day-old BrdU(+) cells. The hippocampal BDNF levels were reduced in EW mice and OVX mice. TrkB receptor inhibitor K252a reduced the density of DCX(+) fibers in HSP mice without the reduction of 28-day-old BrdU(+) cells, or the production of affective disorder. Collectively, these results indicate that postpartum estrogen withdrawal impairs hippocampal neurogenesis in mice that show depression- and anxiety-like behaviors. PMID- 26803530 TI - The mechanisms shaping the single-cell transcriptional landscape. AB - Recent technological and computational advances in understanding the transcriptional and chromatin features of single cells have begun answering longstanding questions in the extent and impact of biological heterogeneity. Here, we outline the intrinsic and extrinsic mechanisms that underlie the transcriptional and functional diversity within superficially homogeneous populations, and we discuss how fascinating new studies have afforded novel insight into each mechanism. The studies are chosen in part to include initial reports of novel functional genomics tools where the eventual applications will clearly have profound impact on our understanding the dynamics of cell-to-cell transcriptional variation-from individual cells to whole organisms. PMID- 26803528 TI - The influence of motherhood on neural systems for reward processing in low income, minority, young women. AB - OBJECTIVE: Given the association between maternal caregiving behavior and heightened neural reward activity in experimental animal studies, the present study examined whether motherhood in humans positively modulates reward processing neural circuits, even among mothers exposed to various life stressors and depression. METHODS: Subjects were 77 first-time mothers and 126 nulliparous young women from the Pittsburgh Girls Study, a longitudinal study beginning in childhood. Subjects underwent a monetary reward task during functional magnetic resonance imaging in addition to assessment of current depressive symptoms. Life stress was measured by averaging data collected between ages 8-15 years. Using a region-of-interest approach, we conducted hierarchical regression to examine the relationship of psychosocial factors (life stress and current depression) and motherhood with extracted ventral striatal (VST) response to reward anticipation. Whole-brain regression analyses were performed post-hoc to explore non-striatal regions associated with reward anticipation in mothers vs nulliparous women. RESULTS: Anticipation of monetary reward was associated with increased neural activity in expected regions including caudate, orbitofrontal, occipital, superior and middle frontal cortices. There was no main effect of motherhood nor motherhood-by-psychosocial factor interaction effect on VST response during reward anticipation. Depressive symptoms were associated with increased VST activity across the entire sample. In exploratory whole brain analysis, motherhood was associated with increased somatosensory cortex activity to reward (FWE cluster forming threshold p<0.001). CONCLUSIONS: These findings indicate that motherhood is not associated with reward anticipation-related VST activity nor does motherhood modulate the impact of depression or life stress on VST activity. Future studies are needed to evaluate whether earlier postpartum assessment of reward function, inclusion of mothers with more severe depressive symptoms, and use of reward tasks specific for social reward might reveal an impact of motherhood on reward system activity. PMID- 26803531 TI - A Comparison of High and Low Dosages of a Component of Milieu Teaching Strategies for Two Preschool-Age Learners With Autism Spectrum Disorder. AB - PURPOSE: The intersection of treatment intensity and communication intervention is an emerging area of investigation. Milieu teaching (MT) approaches for teaching communication skills to children with autism spectrum disorder (ASD) have a substantial evidence base (see Goldstein, 2002). However, a relatively small percentage (37.8%) of MT studies have fully detailed the parameters that are required to determine treatment intensity (Parker-McGowan et al., 2014). This study compared the effect of two dosages of the modeling component of milieu teaching on acquisition and maintenance of new vocabulary for two preschoolers with ASD. METHOD: Low- and high-dosage conditions were compared within an adapted alternating treatments design. Participants were two preschool-age children with ASD. RESULTS: Results suggested a functional relationship between dose of MT models and acquisition of vocabulary items. For 1 participant, a high-dose application yielded more efficient acquisition. For the second participant, a low dose application yielded more efficient acquisition. CONCLUSION: The results of this study highlight the influence of individual differences in ostensibly similar persons and response to intervention. The need for better quantifying dosage parameters and examining the relationship between dosage and intervention approaches for preschool-age learners with ASD is discussed. PMID- 26803532 TI - Comparing the effect of DSM-congruent traumas vs. DSM-incongruent stressors on PTSD symptoms: A meta-analytic review. AB - Experts have long debated how to define the PTSD traumatic stressor criterion. Prior research demonstrates that PTSD symptoms (PTSS) sometimes stem from events that do not meet the DSM requirements for Criterion A (e.g., divorce, bereavement, illness). This meta-analysis of 22 studies examined whether PTSS differ for DSM-congruent criterion A1 traumatic events vs. DSM-incongruent events. The overall effect was significant, albeit small, suggesting that PTSS were greater for individuals who experienced a DSM-congruent event; heterogeneity analyses also indicated further exploration. Two significant moderators emerged: assessment of both A1 and A2 (vs. A1 alone) yielded a significant effect for higher PTSS following traumas vs. stressors. Likewise, self-report assessment of life threat (Criterion A1)-vs. rater or a priori assessment of A1-yielded a significant effect for higher PTSS following traumas. Our results indicate that higher levels of PTSS develop following traumas, and highlight important methodological moderators that may affect this relationship. PMID- 26803533 TI - Abdominal Mondor disease mimicking acute appendicitis. AB - INTRODUCTION: Mondor disease (MD), a superficial thrombophlebitis of the thoraco epigastric veins and their confluents is rarely reported in the literature. The superior epigastric vein is the most affected vessel but involvement of the inferior epigastric vessels or their branches have also been described. There is no universal consensus on treatment in the literature but most authors suggest symptomatic treatment with non-steroid anti-inflammatory drugs (NSAIDs). CASE REPORT: We report the case of a marathon runner who presented with right iliac fossa pain mimicking the clinical symptomatology of an acute appendicitis. The history and the calculated Alvarado score were not in favor of an acute appendicitis. This situation motivated multiple investigations and we finally arrived at the diagnosis of MD. DISCUSSION: Acute appendicitis (AA) is the most common cause of surgical emergencies and one of the most frequent indications for an urgent abdominal surgical procedure around the world. In some cases, right lower quadrant pain remains unclear in spite of US, CT scan, and exclusion of urological and gynecological causes, thus we need to think of some rare pathologies like MD. CONCLUSION: MD is often mentioned in the differential diagnosis of breast pathologies but rarely in abdominal pain assessment. It should be mentioned in the differential diagnosis of the right lower quadrant pain when the clinical presentation is unclear and when acute appendicitis has been excluded. Awareness of MD can avoid misdiagnosis and decrease extra costs by sparing unnecessary imaging. PMID- 26803534 TI - Myxoma Virus Induces Ligand Independent Extrinsic Apoptosis in Human Myeloma Cells. AB - INTRODUCTION: Multiple myeloma is a clonal malignancy of plasma B cells. Although recent advances have improved overall prognosis, virtually all myeloma patients still succumb to relapsing disease. Therefore, novel therapies to treat this disease remain urgently needed. We have recently shown that treatment of human multiple myeloma cells with an oncolytic virus known as myxoma results in rapid cell death even in the absence of viral replication; however, the specific mechanisms and pathways involved remain unknown. MATERIALS AND METHODS: To determine how myxoma virus eliminates human multiple myeloma cells, we queried the apoptotic pathways that were activated after viral infection using immunoblot analysis and other cell biology approaches. RESULTS: Our results indicate that myxoma virus infection initiates apoptosis in multiple myeloma cells through activation of the extrinsic initiator caspase-8. Caspase-8 activation subsequently results in cleavage of BH3 interacting-domain death agonist and loss of mitochondrial membrane potential causing secondary activation of caspase-9. Activation of caspase-8 appears to be independent of extrinsic death ligands and instead correlates with depletion of cellular inhibitors of apoptosis. We hypothesize that this depletion results from virally mediated host-protein shutoff because a myxoma construct that overexpresses the viral decapping enzymes displays improved oncolytic potential. CONCLUSION: Taken together, these results suggest that myxoma virus eliminates human multiple myeloma cells through a pathway unique to oncolytic poxviruses, making it an excellent therapeutic option for the treatment of relapsed or refractory patients. PMID- 26803535 TI - Anaphylaxis to the amoxicillin skin prick test: utility of the basophil activation test in diagnosis. PMID- 26803536 TI - Prevalence and clinical correlation of serum immunoglobulin E in patients with chronic spontaneous urticaria. PMID- 26803537 TI - Regional differences in vitamin D levels and incidence of food-induced anaphylaxis in South Korea. AB - BACKGROUND: Previous studies have suggested low vitamin D as a potential risk factor for food allergy/anaphylaxis. However, few studies have investigated the association between vitamin D and food-induced anaphylaxis (FIA) in South Korea. OBJECTIVE: To examine regional differences in serum vitamin D levels and FIA incidence. METHODS: We used nationwide data collected from 2011 to 2013. Data on vitamin D were obtained from the Korea National Health and Nutrition Examination Survey; data on FIA were obtained from the Health Insurance and Assessment Service. Districts were grouped into region 1 (lower solar radiation) and region 2 (higher solar radiation). We examined differences in FIA incidence and vitamin D levels between the regions, adjusting for age. RESULTS: The study included 2,814 patients with FIA and 15,367 people with available serum vitamin D measurements. Age-adjusted FIA incidence was 2.2 per 100,000 person-years in region 1 and 1.8 per 100,000 person-years in region 2 (relative risk, 1.23; 95% confidence interval, 1.09-1.39). Age-adjusted serum vitamin D levels were 16.5 ng/mL in region 1 and 17.8 ng/mL in region 2 (mean difference, 1.3 ng/mL; 95% confidence interval, 0.9-1.9). After stratification by age, sex, and area of residence, region 1 still had higher FIA incidence and lower vitamin D levels than region 2. CONCLUSION: The present study found a higher incidence of FIA in regions with lower vitamin D levels in the population. Further investigation is necessary to identify any direct associations between vitamin D and food allergy/anaphylaxis. PMID- 26803538 TI - Effectiveness of omalizumab in severe solar urticaria. PMID- 26803539 TI - Applying the WHO conceptual framework for the International Classification for Patient Safety to a surgical population. AB - OBJECTIVE: Efforts to improve patient safety are challenged by the lack of universally agreed upon terms. The International Classification for Patient Safety (ICPS) was developed by the World Health Organization for this purpose. This study aimed to test the applicability of the ICPS to a surgical population. DESIGN: A web-based safety debriefing was sent to clinicians involved in surgical care of abdominal organ transplant patients. A multidisciplinary team of patient safety experts, surgeons and researchers used the data to develop a system of classification based on the ICPS. Disagreements were reconciled via consensus, and a codebook was developed for future use by researchers. RESULTS: A total of 320 debriefing responses were used for the initial review and codebook development. In total, the 320 debriefing responses contained 227 patient safety incidents (range: 0-7 per debriefing) and 156 contributing factors/hazards (0-5 per response). The most common severity classification was 'reportable circumstance,' followed by 'near miss.' The most common incident types were 'resources/organizational management,' followed by 'medical device/equipment.' Several aspects of surgical care were encompassed by more than one classification, including operating room scheduling, delays in care, trainee related incidents, interruptions and handoffs. CONCLUSIONS: This study demonstrates that a framework for patient safety can be applied to facilitate the organization and analysis of surgical safety data. Several unique aspects of surgical care require consideration, and by using a standardized framework for describing concepts, research findings can be compared and disseminated across surgical specialties. The codebook is intended for use as a framework for other specialties and institutions. PMID- 26803540 TI - Patients' informational needs while undergoing brachytherapy for cervical cancer. AB - OBJECTIVE: To identify informational needs of South African women receiving intracavitary brachytherapy for locally advanced cervical cancer as part of a process to develop guidelines for quality patient-centred care. DESIGN: A prospective, qualitative study with a phenomenological approach. SETTING: Brachytherapy Unit, Department Oncology, Universitas Hospital, Bloemfontein, South Africa. PARTICIPANTS: Purposive sampling was utilized to recruit patients undergoing brachytherapy for cervical cancer from July to December 2012. MAIN OUTCOME MEASURES: Semi-structured, one-to-one interviews were conducted, guided by a theme list. Audio-recorded interviews were conducted in Sesotho, Afrikaans and English by an unaffiliated, multilingual interviewer. The interviews were transcribed, translated and thematic analysis performed. RESULTS: Data saturation was achieved having interviewed 28 participants, aged 30-73 years. Four themes with sub-themes were identified: (i) informational needs, (ii) patient disposition towards treatment, (iii) psychological experience and (iv) physical experience. Findings on patients' informational needs were the overarching theme and form the focus of this article. These informational needs included: providing patients with disease- and treatment-related information in their home language; adequate information concerning possible side-effects, sexual intercourse and pre treatment preparation; and providing patients with informative material as standard procedure. CONCLUSION: The article has identified women's informational needs providing a focus for patient-centred care. Providing patients with sufficient and understandable information could lessen feelings of fear and anxiety towards treatment delivery. Guidelines with a patient-centred approach could thus be developed to be used as a tool to assist members of multidisciplinary teams in providing quality care to this group of women. PMID- 26803541 TI - Becoming a clinician researcher in allied health. AB - Objective Combining research with clinical practice has benefits for health services and practitioners. There is limited information available on strategies used by health professionals to balance research with high clinical service demands. The aims of the present study were to examine how research is initiated and to identify the factors that influence the successful integration of research into a clinical work role. Methods Semistructured recursive-style interviews were conducted with 15 research-active allied health professionals at regional health services using a combination of criterion and purposive sampling. Interviews were recorded, transcribed and analysed using constant comparative techniques to identify dominant themes, which were integrated to create a conceptual model. Results Becoming a clinician researcher involved four phases: (1) a research debut; (2) building momentum; (3) developing a track record; and (4) becoming an established clinician researcher. A research debut was enabled by pre-entry exposure to research or through quality activities, predisposing personal characteristics and research opportunities at work. Quarantined time for research, a research-friendly workplace culture and supportive research relationships enabled a clinician to thrive as a researcher despite the challenges. Conclusion The clinician researcher career trajectory contributes to a better understanding of how a research career commences and develops in clinical settings. It may assist to develop strategies to support research capacity building. What is known about the topic? There are potential benefits for clinicians and health services that flow from incorporating research into clinical roles. Factors that motivate, enable and constrain allied health research in clinical settings have been identified, but little is known about how a research career is initiated and progresses over time. What does this paper add? The present study contributes an important career path understanding to the successful development of research capacity from a clinician perspective. The clinician researcher career trajectory delineates four phases and identifies enabling and constraining factors. The study highlights the combination of factors that can initiate a research debut and lead clinicians to thrive as researchers. What are the implications for practitioners? Conducting research can provide an opportunity for a professional challenge and increased job satisfaction. A research-friendly environment, supportive research relationships and quarantined time for research contribute to research output in clinical settings. PMID- 26803542 TI - Lateral Lumbar Interbody Fusion: A Better, Worse, and Similar Approach to Lumbar Arthrodesis. PMID- 26803543 TI - Current Strategies in Anesthesia and Analgesia for Total Knee Arthroplasty. AB - Total knee arthroplasty is associated with substantial postoperative pain that may impair mobility, reduce the ability to participate in rehabilitation, lead to chronic pain, and reduce patient satisfaction. Traditional general anesthesia with postoperative epidural and patient-controlled opioid analgesia is associated with an undesirable adverse-effect profile, including postoperative nausea and vomiting, hypotension, urinary retention, respiratory depression, delirium, and an increased infection rate. Multimodal anesthesia--incorporating elements of preemptive analgesia, neuraxial perioperative anesthesia, peripheral nerve blockade, periarticular injections, and multimodal oral opioid and nonopioid medications during the perioperative and postoperative periods--can provide superior pain control while minimizing opioid-related adverse effects, improving patient satisfaction, and reducing the risk of postoperative complications. PMID- 26803544 TI - Arthroscopic Management of Osteoarthritis. AB - Arthroscopic surgery is commonly performed in the knee, shoulder, elbow, and hip. However, the role it plays in the management of osteoarthritis is controversial. Routine arthroscopic management of osteoarthritis was once common, but this practice has been recently scrutinized. Although some believe that there is no role for arthroscopic treatment in the management of osteoarthritis, it may be appropriate and beneficial in certain situations. The clinical success of such treatment may be rooted in appropriate patient selection and adherence to a specific surgical technique. Arthroscopy may serve as an effective and less invasive option than traditional methods of managing osteoarthritis. PMID- 26803545 TI - Lateral Lumbar Interbody Fusion: Indications, Outcomes, and Complications. AB - Lateral lumbar interbody fusion is a minimally invasive spinal fusion technique that uses the retroperitoneal approach to the anterior spinal column. Mechanical and technical results of the technique compare favorably with those of anterior lumbar interbody fusion in regard to large graft placement, graft volumes, and early initial stability. Lateral lumbar interbody fusion uses the transpsoas approach and traverses near the lumbar plexus. It is not, however, without its unique complications. Groin pain or numbness is well tolerated and often temporary; however, quadriceps palsy can be long-lasting and debilitating. Rarer but serious complications include vascular and visceral injury. Lateral lumbar interbody fusion has been used successfully to treat common degenerative spinal conditions such as spinal instability, stenosis, scoliosis, and degenerative disk disease. While understanding of the lumbar plexus and the technical challenges of the procedure improves, lateral lumbar interbody fusion will continue to provide safe and successful clinical outcomes with less morbidity than traditional procedures. PMID- 26803546 TI - Orthobiologics in Foot and Ankle Surgery. AB - Exploration into the molecular aspects of the healing process has led to the development of autologous and recombinant biologic agents. These products, collectively known as orthobiologics, have the potential to optimize favorable outcomes with respect to bone and soft-tissue restoration and to maximize the natural healing response. These orthobiologics include platelet-derived growth factor, bone morphogenetic proteins, and platelet-rich plasma. Although the usefulness of these growth factors is well described in various fields of surgery, few data exist to support or oppose the specific application of growth factors in foot and ankle surgery. PMID- 26803547 TI - AAOS Appropriate Use Criteria: Management of Pediatric Supracondylar Humerus Fractures With Vascular Injury. PMID- 26803548 TI - Psychometric properties of a 20-item version of the Maternal-Fetal Attachment Scale in a sample of Italian expectant women. AB - OBJECTIVE: the Maternal-Fetal Attachment Scale (MFAS), a 24-item self-report questionnaire to measure the antenatal maternal feeling towards the unborn baby, was introduced by Mecca Cranley in 1981. Despite the widespread use of the questionnaire in clinical and research contexts, issues exist about its psychometric properties. An analysis of the literature showed the need for studies aimed at reviewing the MFAS by eliminating some items and modifying and "modernising" others. This study started from these suggestions and aimed to investigate the psychometric properties of a modified 20-item Italian version of the scale. DESIGN: the original MFAS was back translated and then administered to a pilot sample of 20 pregnant women in order to identify items hard to understand, inappropriate or ambiguous. On the basis of qualitative information derived from this pilot phase, we developed a 20-item Italian version of the MFAS that was later administered to a large sample of pregnant women. SETTING: antenatal education classes carried out in public and private structures of Italian central and insular regions. PARTICIPANTS: a sample of 482 women in middle and late pregnancy, attending antenatal education classes between February 2013 and October 2014. MEASUREMENTS: the modified MFAS was administered together with other scales measuring maternal-fetal attachment, psychological well-being, relational variables. Internal consistencies were evaluated using Cronbach's alpha. Nomological validity was assessed via Pearson correlations. Exploratory and confirmatory factor analyses were used to test the factor structure. FINDINGS: the hypothesised relationships with external criteria were partially substantiated. Exploratory factor analyses suggested a three-dimensional structure. Confirmatory factor analyses provided general support for an oblique three-factor model. Internal consistency was adequate for the total scale and for two of the three subscales. KEY CONCLUSION AND IMPLICATIONS FOR PRACTICE: the 20 item Italian version of the MFAS is a reliable measure of maternal attachment to the fetus in Italian women. Cranley's five dimensions were not confirmed; instead, three factors emerged that could be renamed 'Future parental roletaking', 'Present interaction with the baby' and 'Giving of self and responsibility to the unborn child'. As maternal-fetal attachment is considered a predictor of the quality of the postnatal mother-child relationship, the MFAS could be a helpful tool in pre- and perinatal research and midwifery care to develop prevention programs based on women specific needs. Moreover, the availability of this questionnaire can assist in expanding research and in facilitating trans cultural comparison in issues related to pregnancy. PMID- 26803549 TI - The cognitive nexus between Bohr's analogy for the atom and Pauli's exclusion schema. AB - The correspondence principle is the primary tool Bohr used to guide his contributions to quantum theory. By examining the cognitive features of the correspondence principle and comparing it with those of Pauli's exclusion principle, I will show that it did more than simply 'save the phenomena'. The correspondence principle in fact rested on powerful analogies and mental schemas. Pauli's rejection of model-based methods in favor of a phenomenological, rule based approach was therefore not as disruptive as some historians have indicated. Even at a stage that seems purely phenomenological, historical studies of theoretical development should take into account non-formal, model-based approaches in the form of mental schemas, analogies and images. In fact, Bohr's images and analogies had non-classical components which were able to evoke the idea of exclusion as a prohibition law and as a preliminary mental schema. PMID- 26803550 TI - Study design of J-ELD AF: A multicenter prospective cohort study to investigate the efficacy and safety of apixaban in Japanese elderly patients. AB - BACKGROUND: Apixaban, one of the non-vitamin K antagonist oral anticoagulants, was reported to be effective and safe in stroke prevention in patients with atrial fibrillation (AF) based on the global randomized clinical trial, but data are limited on the efficacy and safety of apixaban in Japanese elderly patients. METHODS AND RESULTS: The J-ELD AF Registry is a large-scale, contemporary observational study, continuously and prospectively registering elderly Japanese patients with AF aged 75 years or older who are currently taking apixaban or the elderly who are to receive apixaban in daily clinical practice, and accumulating the outcomes during one-year follow-up period. In addition to standard baseline characteristics, prothrombin time and anti-Xa activity will be measured to investigate the biomarker characteristics. The primary efficacy endpoints will be stroke and systemic embolism, and the primary safety endpoint will be major bleeding requiring hospitalization. The secondary endpoints in this study will be all-cause death, cardiovascular death, acute myocardial infarction, and the composite of stroke/systemic embolism, cardiovascular death, and acute myocardial infarction. As a primary analysis, the primary/secondary endpoints in the enrolled patients will be totalized for the entire group, and the incidence of events will be described by age, CHADS2 score, HAS-BLED score, and apixaban dose (5 or 2.5mg bid). The factors that independently predict the incidence of the primary/secondary endpoints will be searched for by Cox regression. The relationship between the biomarkers and the primary/secondary endpoints will also be examined in an explorative manner. CONCLUSION: This study will provide important information on the efficacy and safety of apixaban in elderly Japanese patients aged 75 years or older, and those of low-dose administration of apixaban (2.5mg bid) for which many of the Japanese elderly are indicated. PMID- 26803551 TI - Active magnetic bearings used as exciters for rolling element bearing outer race defect diagnosis. AB - The active health monitoring of rotordynamic systems in the presence of bearing outer race defect is considered in this paper. The shaft is assumed to be supported by conventional mechanical bearings and an active magnetic bearing (AMB) is used in the mid of the shaft location as an exciter to apply electromagnetic force to the system. We investigate a nonlinear bearing-pedestal system model with the outer race defect under the electromagnetic force. The nonlinear differential equations are integrated using the fourth-order Runge Kutta algorithm. The simulation and experimental results show that the characteristic signal of outer race incipient defect is significantly amplified under the electromagnetic force through the AMBs, which is helpful to improve the diagnosis accuracy of rolling element bearing's incipient outer race defect. PMID- 26803552 TI - Discriminative sparse subspace learning and its application to unsupervised feature selection. AB - In order to efficiently use the intrinsic data information, in this study a Discriminative Sparse Subspace Learning (DSSL) model has been investigated for unsupervised feature selection. First, the feature selection problem is formulated as a subspace learning problem. In order to efficiently learn the discriminative subspace, we investigate the discriminative information in the subspace learning process. Second, a two-step TDSSL algorithm and a joint modeling JDSSL algorithm are developed to incorporate the clusters' assignment as the discriminative information. Then, a convergence analysis of these two algorithms is provided. A kernelized discriminative sparse subspace learning (KDSSL) method is proposed to handle the nonlinear subspace learning problem. Finally, extensive experiments are conducted on real-world datasets to show the superiority of the proposed approaches over several state-of-the-art approaches. PMID- 26803553 TI - The effect of conduction velocity slowing in left ventricular midwall on the QRS complex morphology: A simulation study. AB - Midwall fibrosis is a frequent finding in different types of left ventricular hypertrophy. Fibrosis presents a local conduction block that can create a substrate for ventricular arrhythmias and lead to the continuous generation of reentry. Having also impact on the sequence of ventricular activation it can modify the shape of QRS complex. In this study we simulated the effects of slowed conduction velocity in the midwall in the left ventricle and in its anteroseptal region on the QRS morphology using a computer model. MATERIAL AND METHODS: The model defines the geometry of cardiac ventricles analytically as parts of ellipsoids; the left ventricular wall is represented by five layers. The impulse propagation velocity was decreased by 50% in one and two midwall layers, respectively, in the whole left ventricle and in LV anterior region. The effects of slowed conduction velocity on the QRS complex of the 12-lead electrocardiogram are presented as 12-lead electrocardiograms and corresponding values of ECG criteria for left ventricular hypertrophy (ECG-LVH criteria): Gubner criterion, Sokolow-Lyon index (SLI) and Cornell voltage. RESULTS: All simulated situations led to increased R wave amplitude in the lead I and of S wave in the lead III, showing a leftward shift of the electrical axis and increased values of ECG-LVH criteria based on limb leads alone or in combination with precordial leads (Gubner criterion, Cornell voltage). The slowed conduction velocity in the whole LV influenced the QRS complex voltage in precordial leads, having an impact on the SLI and Cornell voltage. The changes were pronounced if two layers were involved. CONCLUSION: Using computer modeling we showed that the midwall slowing in conduction velocity modified the QRS complex morphology. The QRS complex changes were consistent with ECG-LVH criteria, i.e. QRS patterns usually interpreted as the effect of left ventricular hypertrophy (the increased left ventricular mass). PMID- 26803554 TI - A porcine model of early atrial fibrillation using a custom-built, radio transmission-controlled pacemaker. AB - Mechanisms underlying atrial remodeling toward atrial fibrillation (AF) are incompletely understood. We induced AF in 16 pigs by 6weeks of rapid atrial pacing (RAP, 600bpm) using a custom-built, telemetrically controlled pacemaker. AF evolution was monitored three times per week telemetrically in unstressed, conscious animals. We established a dose-response relationship between RAP duration and occurrence of sustained AF >60minutes. Left atrial (LA) dilatation was present already at 2weeks of RAP. There was no evidence of left ventricular heart failure after 6weeks of RAP. As a proof-of-principle, arterial hypertension was induced in 5/16 animals by implanting desoxycorticosterone acetate (DOCA, an aldosterone-analog) subcutaneously to accelerate atrial remodeling. RAP+DOCA resulted in increased AF stability with earlier onset of sustained AF and accelerated anatomical atrial remodeling with more pronounced LA dilatation. This novel porcine model can serve to characterize effects of maladaptive stimuli or protective interventions specifically during early AF. PMID- 26803555 TI - ETA and ETB receptors contribute to neuropeptide Y-induced secretion of endothelin-1 in right but not left human ventricular endocardial endothelial cells. AB - Our recent work showed that neuropeptide Y-induced secretion of endothelin-1 (ET 1) in left and right human ventricular endocardial endothelial cells (hLEECs or hREECs respectively) via the activation of neuropeptide Y2 or Y5 receptors depending on the cell type. The aim of this study was to verify whether hLEECs or hREECs secretion of ET-1 induced by NPY is due, in part, to the activation of ETA and/or ETB receptors by the secreted ET-1. Using the technique of indirect immunofluorescence coupled to real 3-D confocal microscopy, as well as ELISA, our results show that in hREECs, the NPY-induced release of ET-1 seems to be due, in part, to the activation of both ETA and ETB receptors. On the other hand, in hLEECs, ETA and ETB receptors do not contribute to the ET-1 released by NPY. Therefore, our results suggest that the NPY-induced release of ET-1 in EECRs is due to NPY receptor activation and the subsequent activation of the ETA and ETB receptors by the released ET-1. However, the release of ET-1 by NPY in hLEECs is mainly due to NPY receptor activation. Furthermore, this secretory process of ET 1 is different between the right and left ventricular cells and highlights the important tuning roles that right and left ventricular EECs possess as well as their contribution to the physiological and pathophysiological states of the underlying heart muscle. PMID- 26803556 TI - Adverse events in faecal microbiota transplant: a review of the literature. AB - BACKGROUND: Faecal microbiota transplant (FMT) is the infusion of donor faeces into the gut with the aim of improving microbial diversity. The procedure has gained significant interest recently in the treatment of recurrent Clostridium difficile infection (CDI). The literature is currently dominated by small case series and isolated case reports. There is no standardization of methods and recording of outcomes. AIM: To present the adverse events that have been associated with the use of FMT, as reported in the English literature to date. METHODS: A database search of Medline and Embase identified publications where FMT has been administered. Review articles were excluded. In total, 109 publications were identified that described the use of FMT in 1555 individuals. FINDINGS: Other than three small randomized controlled studies, the data consisted of small series and case reports. CDI was the most common indication for FMT (N = 1190), with the majority of the remaining cases receiving FMT for inflammatory bowel disease. FMT had also been applied for irritable bowel syndrome, metabolic syndrome and constipation in small numbers. Adverse events appear to be uncommon, often mild and self-limiting; however, serious adverse events including bacteraemia, perforations and death have been reported. CONCLUSION: The vast majority of adverse events of FMT appear to be mild, self limiting and gastrointestinal in nature. In some cases, a credible association was not established due to the lack of controlled data. There is a need for standardized, randomized controlled trials to qualify and quantify the risks associated with FMT. PMID- 26803557 TI - Imaging techniques for evaluation of uterine myomas. AB - Due to their high prevalence and related morbidity, uterine myomas constitute a group of gynecological pathologies largely studied in all clinical, diagnostic, and therapeutic aspects. They have been widely evaluated with a large series of imaging techniques. In fact, ultrasound (also saline infusion sonohysterography) and magnetic resonance imaging (MRI) are considered the optimal methods to assess uterine fibroids in terms of number, volume, echostructure, location, relation with endometrial cavity and uterine layers, vascularization, and differential diagnosis with other benign (adenomyosis) and malignant myometrial pathologies. Nevertheless, further studies are required to fill some gaps such as the absence of a common and sharable sonographic terminology and methodology to scan the myometrium, as well as imaging parameters for differentiation of typical myomas from smooth tumors of unknown malignant potential (STUMP) and leiomyosarcomas. PMID- 26803559 TI - Human neural progenitor cells in central nervous system lesions. AB - Various immature cells can be isolated from human embryonic and fetal central nervous system (CNS) residual tissue and potentially be used in cell therapy for a number of neurological diseases and CNS insults. Transplantation of neural stem and progenitor cells is essential for replacing lost cells, particularly in the CNS with very limited endogenous regenerative capacity. However, while dopamine released from transplanted cells can substitute the lost dopamine neurons in the experimental models of Parkinson's disease, stem and progenitor cells primarily have a neuroprotective effect, probably through the release of trophic factors. Understanding the therapeutic effects of transplanted cells is crucial to determine the design of clinical trials. During the last few years, a number of clinical trials for CNS diseases and insults such as amyotrophic lateral sclerosis (ALS), stroke, and spinal cord trauma using neural progenitor cells have been initiated. Data from these early studies will provide vital information on the safety of transplanting these cells, which still is a major concern. That the beneficial results observed in experimental models also can be repeated in the clinical setting is highly hoped for. PMID- 26803558 TI - Abnormal uterine bleeding. AB - Abnormal uterine bleeding (AUB) is a common and debilitating condition with high direct and indirect costs. AUB frequently co-exists with fibroids, but the relationship between the two remains incompletely understood and in many women the identification of fibroids may be incidental to a menstrual bleeding complaint. A structured approach for establishing the cause using the Federation International de Gynecologie et d'Obstetrique (FIGO) PALM-COEIN (Polyp, Adenomyosis, Leiomyoma, Malignancy (and hyperplasia), Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic and Not otherwise classified) classification system will facilitate accurate diagnosis and inform treatment options. Office hysteroscopy and increasing sophisticated imaging will assist provision of robust evidence for the underlying cause. Increased availability of medical options has expanded the choice for women and many will no longer need to recourse to potentially complicated surgery. Treatment must remain individualised and encompass the impact of pressure symptoms, desire for retention of fertility and contraceptive needs, as well as address the management of AUB in order to achieve improved quality of life. PMID- 26803560 TI - Comparison of patient-reported outcomes between immediately and conventionally loaded mandibular two-implant overdentures: A preliminary study. AB - PURPOSE: The aim of this preliminary study is to compare patient-reported outcomes between immediately and conventionally loaded mandibular two-implant overdentures retained by magnetic attachments. METHODS: Nineteen participants with edentulous mandibles were randomly assigned into either an immediate loading group (immediate group) or a conventional loading group (conventional group). Each participant received 2 implants in the inter-foraminal region by means of flapless surgery. Prostheses in the immediate and conventional groups were loaded using magnetic attachments on the same day as implant placement or 3 months after surgery, respectively. All participants completed questionnaires (the Japanese version of the Oral Health Impact Profile for edentulous [OHIP-EDENT-J], the patient's denture assessment [PDA], and general satisfaction) before implant placement (baseline) and 1, 2, 3, 4, 5, 6, and 12 months after surgery. The median differences between baseline and each monthly score were compared using the Mann-Whitney U test. The differences in median and 95% confidence interval between two groups were analyzed. RESULTS: The immediate group showed slightly lower OHIP-EDENT-J summary score at 1 and 3 months than the conventional group (P=0.09). In the lower denture domain of PDA, the immediate group showed a statistically higher score at 3 months (P=0.04). There was no statistically significant difference in general satisfaction between the two groups. CONCLUSIONS: Based on this preliminary study, immediate loading of mandibular two implant overdentures with magnetic attachments tends to improve oral health related quality of life and patient assessment earlier than observed with a conventional loading protocol. PMID- 26803561 TI - Pressure dynamics in the trays caused by differences of the various impression materials and thickness of the relief in the maxillary edentulous model. AB - PURPOSE: The purpose of this study is to compare the pressure dynamics in the trays caused by differences in the various impression materials and in the thickness of the relief provided for the trays. METHODS: In this study, two types of polyvinylsiloxane elastomers, one type of polyether elastomer and one type of alginate impression material were used. Pressure sensors were embedded at eight locations in a model of an edentulous maxilla, and used a simulation model covered with a pseudomucosa. For each impression material, the measurement was performed five times for each of the three types of trays, and the mean values were determined. Statistical analysis was carried out using one-way analysis of variance and the Tukey's HDS method, and the various pressure sensor values for each of the impression materials were compared 10s and 20s after the start of the measurement. Additionally, we compared differences among the three types of trays after 20s. RESULTS: The pressure values for sensors placed in the relief region tended to become uniform. Furthermore, we saw a tendency for the pressure to increase at the alveolar crests of the first molars on the left and right and at the posterior border of the palate, all of which support the denture, when relief was provided. CONCLUSIONS: The above results suggest that making the final impression for the denture using the selective pressure technique, with consideration given to the pressure dynamic, may lead to a good outcome in terms of preservation of the alveolar ridge. PMID- 26803562 TI - Parents' Perceived Satisfaction of Care, Communication and Environment of the Pediatric Intensive Care Units at a Tertiary Children's Hospital. AB - This study aims to identify parental perceptions on pediatric intensive care related satisfaction within three domains: environment, child's care provided and communication. In addition, it aims to identify whether parent's socio demographics and child's clinical variables predict parents' perceived satisfaction. In this study, a total of 123 parents whose child received care in the PICU of a tertiary children's hospital in Amman completed the Arabic version of the parents satisfaction survey (PSS). A cross-sectional, descriptive correlational design was used to collect data. All data were collected between June and October of 2013. Central tendency measures and percentages of replies for each domain revealed that at least 7 items were rated poorly satisfied. More than half of the parents were not satisfied with the noise level of the PICU, the time nurses spent at the child's bedside, as well as the way the healthcare team prepare them for the child's admission. Almost 90% of the parents believed that the nurses ignored their child's needs by not listening to parents and by responding slowly to child's needs. Stepwise regression analysis showed that that the number of hospital admissions, health insurance and the severity of illness was the main predictor of parents' satisfaction. In conclusion, the availability of health care professionals, the support and the information they share with the child's parents are all significant to parent's satisfaction and hence to better quality of care. Targeting the domains of low satisfaction reported by the parents could increase parent's satisfaction and achieve quality improvement required for this population. PMID- 26803563 TI - An automatic segmentation system of acetabulum in sequential CT images for the personalized artificial femoral head design. AB - This paper describes an automatic and accurate segmentation method to extract the acetabulum tissue from sequential CT images. The hip joint consists of acetabulum and femoral head. In the personalized femoral head prosthesis designing by reverse engineering technology, obtaining the accurate acetabulum shape is the most important task. However, due to the necrotic femoral head's complex shape and the extremely narrow inter-bone region, obtaining the accurate acetabulum shape remains a challenging work. In this paper, we overcame these difficulties and developed an automatic segmentation method. First, we obtain the rough contour of the femoral head by utilizing the constraints of the great trochanter and the shape of femoral head in the initial slice. Second, we refine the rough contour by an orthogonal line edge detection approach and obtain a refined contour which will be used as the initial contour of the snake algorithm. Then, the snake algorithm is performed slice by slice upwards and downwards to generate the adjacent contours. During this process, the contour of the femoral head in a segmented slice is used as the initial contour of the next unsegmented slice. Finally, we can obtain the accurate sequential contours of the acetabulum by removing the femoral head and the femoral regions. And the 3D models of the acetabulum can be obtained correspondingly. The experimental result shows that the 3D models obtained by the proposed method are accurate and satisfactory. On this condition, we can reconstruct the personalized femoral head 3D models and design the personalized femoral head prosthesis. PMID- 26803564 TI - [Lung cancer molecular testing, what role for Next Generation Sequencing and circulating tumor DNA]. AB - Molecular screening has become a standard of care for patients with advanced cancers and impacts on how to treat a patient. Advances in genomic technologies with the development of high throughput sequencing methods will certainly improve the possibilities to access a more accurate molecular diagnosis and to go beyond the identification of validated targets as a large number of genes can be screened for actionable changes. Moreover, accurate high throughput testing may help tumor classification in terms of prognosis and drug sensitivity. Finally, it will be possible to assess tumor heterogeneity and changes in molecular profiles during follow-up using ultra-deep sequencing technologies and circulating tumor DNA characterization. The accumulation of somatic ADN alterations is considered as the main contributing factor in carcinogenesis. The alterations can occur at different levels: mutation, copy number variations or gene translocations resulting in altered expression of the corresponding genes or impaired protein functions. Genes involved are mainly tumor suppressors, oncogenes or ADN repair genes whose modifications in tumors will impinge cell fate and proliferation from tumor initiation to metastasis. The entire genome of various tumor types, have now been sequenced. In lung cancer, the average number of mutations is very high with more than 8.9 mutations/Mb (Network TCGAR, 2014) that is to say more than 10,000 mutations/genome. These alterations need to be classified, indeed, some are true drivers that directly impact proliferation and some are passenger mutations linked to genetic instability. The development of targeted therapies relies on the identification of oncogenic drivers. The identification of genotype phenotype associations as in the case of EGFR-TKI (Epidermal growth factor receptor-tyrosine kinase inhibitor) and EGFR mutations in lung cancer led to the restriction of drugs to patients for which tumor genotype predicts efficacy. Tumor-molecular directed therapy based on validated targets (EGFR, ALK) is in the clinics, rapidly, with the developments of multi-targets or multi-drug assays there will be a need for tumor-molecular-profile directed therapy. Today, there are practical challenges to a successful implementation of NGS technologies for clinical applications. Broadly, some are linked to the tumor (heterogeneity), to the tissue (availability, storage, fixative), to the design of specific assays or set of genes, to the interpretation of non-driver mutations and to a possible access to drugs once a target is identified. Technical challenges are solved, NGS (at least targeted-NGS) plateforms have been validated by INCa labeled laboratories, in this context, we will address different questions: How, for whom, what kind of profiling and what can we expect? PMID- 26803565 TI - [Coil embolization therapy in post-traumatic pseudoaneurysms and arteriovenous fistula of knee and leg arteries]. AB - Pseudoaneurysms remain a rare complication of knee and leg trauma. They may go unnoticed and manifest late after the initial trauma; they are often associated with arteriovenous fistula. No standard treatment is recognized. We report a case of post-traumatic pseudoaneurysm of the inferior articular artery of the knee, treated by coil embolization and a case of post-traumatic pseudoaneurysm of the anterior tibial artery associated with an arteriovenous fistula, treated with coil embolization and decompression surgery. Follow-up in both patients was satisfactory. PMID- 26803566 TI - Timing pediatric ear reconstruction: The case for a range of options. PMID- 26803567 TI - Distally based sural flap: Utility of indocyanine green in the second stage surgery. A case series. PMID- 26803568 TI - Using Ultrasound to Prevent Screw Penetration. AB - Ultrasound is a readily available, inexpensive, easy-to-use, and rapid diagnostic tool. Physicians can use ultrasound to identify excessively long screws or screw penetration into joints. This article illustrates ultrasound identification of problem screws. PMID- 26803569 TI - Collagenase Treatment for Dupuytren Disease of the Thumb and First Web. AB - PURPOSE: To evaluate the short-term effectiveness of collagenase Clostridium histolyticum to treat thumb and first web contractures in Dupuytren disease. METHODS: We prospectively included 14 thumbs in 12 patients with a contracture at the metacarpophalangeal or interphalangeal joint of at least 20 degrees with a palpable cord in the thumb (n = 8) or an adduction contracture of the thumb with palpable cords in the first web (n = 6). They received an injection containing 0.58 mg of collagenase Clostridium histolyticum in the fibrous cord divided over 3 spots. The contracture was released by carefully manipulating the thumb under local anesthesia 1 day later. The extension and abduction deficits were measured before and after the intervention (follow-up at 7 and 30 days and 6 months). Wilcoxon signed rank test was used to analyze the data. RESULTS: In the total sample, postintervention extension deficits were statistically significantly lower than preintervention deficits except in one patient who had a recurrence at 6 months compared with the 30-day posttreatment result. Intermetacarpophalangeal head distance (IMD) also improved significantly. In an analysis of subgroups, we compared the separate contributions of treatment of a pretendinous cord and a first web cord on both extension deficit and IMD. Treatment of pretendinous cords significantly affected both extension deficit and IMD. However, treatment of first web contractures did not significantly improve extension or IMD. CONCLUSIONS: Collagenase Clostridium histolyticum is a good treatment option for pretendinous cords in thumbs affected with Dupuytren disease because it provides good results, is minimally invasive, and has minor adverse events. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 26803570 TI - Intralesional Versus Wide Resection of Low-Grade Chondrosarcomas of the Hand. AB - PURPOSE: To report our experience with intralesional curettage (resection with positive margins) and amputation (resection with negative margins) of low-grade chondrosarcomas (LCS) of the hand. MATERIALS AND METHODS: Skeletally mature patients treated surgically for LCS of the hand at our institutions were reviewed. Demographics and oncological history were collected. Results of the entire cohort and by treatment modality were analyzed radiographically, functionally (strength, Disabilities of the Arm, Shoulder, and Hand measure), cosmetically, and oncologically (recurrence, Musculoskeletal Tumor Society score, metastasis, and mortality rates). RESULTS: Seventeen cases in 16 patients were identified. Nine patients were women. Average age at surgery was 43 years (range, 20-80 years). Mean follow-up was 18 years (range, 9-23 years). Six of the 17 lesions treated at different institutions with intralesional procedures presented as recurrent disease. We treated 3 with a repeat intralesional procedure and the remaining with wide resection. Recurrence incidence was the same in both groups. The remaining 11 new-onset cases were treated with intralesional procedures (6) or wide resections (5). One of the 6 tumors treated with an intralesional procedure recurred. None treated with wide resection recurred. Recurrence incidence combining new- onset and recurrent disease after intralesional procedures was 22% versus 13% for wide resections. Average grip strength was 37 kg (range, 21-55 kg), and pinch strength was 7.6 kg (range, 4.5-12.5 kg). Mean Disabilities of the Arm, Shoulder, and Hand score was 2 (range, 0-10). There were no wound complications, and appearance was satisfactory in most cases (visual analog scale score, > 8). Average Musculoskeletal Tumor Society score was 29 points (range, 21-30 points). No patients presented with metastatic disease or died because of LCS. CONCLUSIONS: Intralesional resections aiming to preserve function are safe, recognizing that more than 1 procedure may be required. Amputation also plays a role with excellent functional outcome in cases in which severe joint deformity or involvement of soft tissues and neurovascular structures interferes with function. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 26803571 TI - Osteochondral Autograft Transplantation Surgery for Metacarpal Head Defects. AB - Post-traumatic osteonecrosis of the metacarpal head is a challenging problem, particularly in younger patients in whom arthroplasty may not be a durable option. Although several osteochondral reconstructive options have been proposed, some are associated with considerable donor site morbidity and/or require the use of internal fixation. We present an application of osteochondral autograft transplantation surgery as a treatment option for focal metacarpal head lesions. An osteochondral plug from the non-weight-bearing articular surface of the knee is transferred and press-fit to resurface a focal metacarpal head defect. The technical pearls and pitfalls are reviewed, and an illustrative case is presented. PMID- 26803572 TI - Technical Results of Vacuum-Assisted Thrombectomy for Arterial Clot Removal in Patients with Acute Limb Ischemia. AB - PURPOSE: To assess the efficacy and safety of a vacuum-assisted thrombectomy (VAT) catheter system for treating patients with acute limb ischemia (ALI). MATERIALS AND METHODS: A retrospective study evaluated VAT systems (Penumbra, Alameda, California) in a consecutive series of 30 patients with ALI. ALI was defined as clinical symptoms within 2 weeks of presentation. The primary endpoint was improvement in blood flow across a lesion by improvement in Thrombolysis in Myocardial Infarction (TIMI) score that was adapted to peripheral arteries. Concomitant balloon angioplasty or stent placement in addition to VAT was considered a complementary treatment. Additional thrombectomy treatments, such as thrombolysis and mechanical thrombectomy, were considered technical failures. Target lesions were grouped anatomically into above-the-knee (ATK) or below-the knee (BTK) lesions. RESULTS: In 30 patients, 33 lesions (ATK, n = 13; BTK, n = 20) were treated. No complications were attributed to the VAT systems. The primary endpoint was obtained in 24/33 (72.7%) lesions (BTK, 17/20 [85.0%]; ATK, 7/13 [53.9%]; P = .050 by chi(2) test). TIMI scores were similar at baseline but differed after VAT between the ATK and BTK groups (P < .025 by t test). ATK lesions required more concomitant angioplasty or stent placement, or both (P < .015 by chi(2) test). CONCLUSIONS: VAT is a safe, technically successful short term therapeutic option for thrombus removal in patients with ALI. PMID- 26803573 TI - Meta-Analysis of Local Endovascular Therapy for Acute Ischemic Stroke. AB - A meta-analysis was performed to assess randomized controlled trials comparing local endovascular therapy (with and without intravenous thrombolysis) versus standard care (intravenous thrombolysis alone when appropriate) for acute ischemic stroke. Local endovascular therapy showed a significant improvement in functional independence versus standard care (odds ratio, 1.779; 95% confidence interval, 1.262-2.507; P < .001). This benefit strengthened further on subgroup analyses of trials in which a majority of cases used stent retrievers, trials with intravenous thrombolysis use in both arms when appropriate, and trials that required preprocedural imaging of all patients. There were no significant differences between arms in terms of mortality, hemicraniectomy, intracranial hemorrhage, and cerebral edema rates (P > .05). In conclusion, in the treatment of acute ischemic stroke, local endovascular therapy leads to improved functional independence compared with standard care. PMID- 26803574 TI - Transarterial Ethanol Ablation for Unresectable Hepatocellular Carcinoma: Analysis of Clinical and Tumor Outcomes. AB - PURPOSE: To evaluate survival, tumor response, and treatment toxicity of transarterial ethanol ablation (TEA) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This prospective study involved 186 patients (146 men and 40 women; median age, 65 y [interquartile range, 57-72.3 y]). Of 186 patients, 146 (78.5%) were hepatitis B virus carriers, 18 (9.7%) were hepatitis C virus carriers, 82 (44.1%) had tumors >= 5 cm, and 43 (23.1%) had multifocal tumors. Overall survival (OS), complete response (CR) by European Association for the Study of the Liver criteria, time to progression (TTP), progression-free survival (PFS), and treatment toxicities were evaluated. Univariate and multivariate analyses for prognostic factors of OS were performed. RESULTS: Median OS was 25.7 months (95% confidence interval [CI], 20.9-30.5) and varied significantly between Child-Pugh A and B (28.7 mo vs 13.4 mo, P < .001), and Barcelona Clinic Liver Cancer A and B or C (37.1 mo vs 17.7 mo, P = .001). Prognostic factors for longer OS were solitary tumor, tumor size < 5 cm, > 1 treatments, and CR of all tumors at 6 months. TTP was 9.1 months (95% CI, 6.9 11.3). PFS was 8.4 months (95% CI, 7.1-9.7). CR occurred in 69.1% (159/230) of lesions and 48.9% (88/180) of patients at 6 months. Any one symptom of the postembolization syndrome of grade 2 severity occurred in < 22% (41/186) of patients. No treatment-related hepatitis or death occurred within 30 days. Transient respiratory decompensation occurred in three patients (1.6% [3/186]), and alcoholic intoxication occurred in one patient (0.5% [1/186]). CONCLUSIONS: TEA appears to be safe and effective for local control of HCC. PMID- 26803575 TI - Pulmonary Artery Imaging in Patients with Chronic Thromboembolic Pulmonary Hypertension: Comparison of Cone-Beam CT and 64-Row Multidetector CT. AB - PURPOSE: To compare the depiction of pulmonary arteries in pulmonary arterial catheter-based contrast-enhanced cone-beam CT with peripheral intravenous contrast-enhanced multidetector CT in patients with suspected chronic thromboembolic pulmonary hypertension. MATERIAL AND METHODS: In 20 patients (15 men and 5 women, 63.4 y +/- 16.3), cone-beam CT using a catheter placed in the main pulmonary artery and 64-row multidetector CT using an appropriate venous access were performed. Contrast enhancement was measured in the main pulmonary artery, the right and left pulmonary arteries, and the left atrium. The amount of peripheral vessel conspicuity adjacent to the pleural surface (distance from vessel-to pleura) was measured. Two readers (R1, R2) independently evaluated the pulmonary arteries for image quality and pathologic findings in both modalities. RESULTS: Contrast density was higher in the main pulmonary artery and right and left pulmonary arteries (P < .002) and lower in the left atrium (P = .001) on cone-beam CT. The smallest distance between clearly delineated vessels and the pleura was significantly lower on cone-beam CT images (P < .0001). Interobserver agreement was good for cone-beam CT (kappa = 0.79) and multidetector CT (kappa = 0.78), whereas intermodality agreement was moderate (R1, kappa = 0.60; R2, kappa = 0.59). Both readers detected more weblike stenoses with cone-beam CT (76; 22%) compared with multidetector CT (25; 7%). CONCLUSIONS: Cone-beam CT shows improved contrast between pulmonary arteries and the left atrium and allows a more detailed depiction of the pulmonary arteries. PMID- 26803577 TI - Synthesis of 4-sulfamoylphenyl-benzylamine derivatives with inhibitory activity against human carbonic anhydrase isoforms I, II, IX and XII. AB - Imine derivatives were obtained by condensation of sulfanilamide with substituted aromatic aldehydes. The Schiff bases were thereafter reduced with sodium borohydride, leading to the corresponding amines, derivatives of 4 sulfamoylphenyl-benzylamine. These sulfonamides were investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). We noted that the compounds incorporating secondary amine moieties showed a better inhibitory activity against all CA isozymes compared to the corresponding Schiff bases. Low nanomolar CA II, IX and XII inhibitors were detected, whereas the activity against hCA I was less potent. The secondary amines incorporating sulfonamide or similar zinc-binding groups, poorly investigated chemotypes for designing metalloenzyme inhibitors, may offer interesting opportunities in the field due to the facile preparation and possibility to explore a vast chemical space. PMID- 26803576 TI - Quality Improvement Guidelines for Percutaneous Nephrostomy. PMID- 26803578 TI - Novel naphtho[2,1-d]oxazole-4,5-diones as NQO1 substrates with improved aqueous solubility: Design, synthesis, and in vivo antitumor evaluation. AB - A new series of ortho-naphthoquinone analogs of beta-lapachone were designed, synthesized and evaluated. The biological results indicated that most of our compounds were efficient substrates for NQO1. The new scaffold with water-soluble side chain resulted in greater solubility under acidic condition compared to beta lapachone. Thus avoiding the use of hydroxylpropyl beta-cyclodextrin which would finally cause the rapid drug clearance from the blood and dose-limiting toxicity in the form of hemolytic anemia. The most soluble and promising compound in this series was 2-((4-benzylpiperazin-1-yl)methyl)naphtho[2,1-d]oxazole-4,5-dione (3k), which inhibited cancer cell (NQO1-rich A549 cell line) growth at IC50 values of 4.6+/-1.0MUmol.L(-1). Furthermore, compound 3k had in vivo antitumor activity in an A549 tumor xenografts mouse model comparable to the activity obtained with beta-lapachone. The results indicated that these ortho naphthoquinones could serve as promising leads for further optimization as novel substrates for NQO1. PMID- 26803579 TI - Occurrence of immunosuppressive drugs and their metabolites in the sewage impacted Vistula and Utrata Rivers and in tap water from the Warsaw region (Poland). AB - Immunosuppresive therapy following organ transplant frequently includes treatment with tacrolimus and mycophenolic acid derivatives. These pharmaceuticals may enter the environment through wastewater treatment plant (WWTP) effluents and may have a potentially harmful effect on aquatic biota. Tacrolimus, mycophenolic acid and their metabolites were measured at specific points of a large Polish river (Vistula), a smaller river (Utrata) and in tap water samples from the Warsaw region. Analysis was performed using liquid chromatography tandem mass spectrometry, after solid phase extraction for water samples, or QuEChERS extraction for sediments. Residues of tacrolimus were below quantitation limits in both water and sediment samples. However, in water samples mycophenolic acid concentrations were measured at up to 180 ng L(-1) downstream of WWTP outfalls. No immunosuppressive drugs were detected in tap water. Concentrations of mycophenolic acid exceeded the predicted no effect concentration (PNEC) value in some Polish surface water, and risk calculations predicted at least twice higher concentrations in some other countries of the European Union. To the best of the authors' knowledge, this is the first report of these immunosuppressive drug concentrations in the environment. PMID- 26803581 TI - Human Metapneumovirus Infection in Children with a History of Prematurity--A Condition Worth More Attention. PMID- 26803580 TI - Atrazine and its main metabolites alter the locomotor activity of larval zebrafish (Danio rerio). AB - Atrazine (ATZ) and its main chlorometabolites, i.e., diaminochlorotriazine (DACT), deisopropylatrazine (DIP), and deethylatrazine (DE), have been widely detected in aquatic systems near agricultural fields. However, their possible effects on aquatic animals are still not fully understood. In this study, it was observed that several developmental endpoints such as the heart beat, hatchability, and morphological abnormalities were influenced by ATZ and its metabolites in different developmental stages. In addition, after 5 days of exposure to 30, 100, 300 MUg L(-1) ATZ and its main chlorometabolites, the swimming behaviors of larval zebrafish were significantly disturbed, and the acetylcholinesterase (AChE) activities were consistently inhibited. Our results also demonstrate that ATZ and its main chlorometabolites are neuroendocrine disruptors that impact the expression of neurotoxicity-related genes such as Ache, Gap43, Gfap, Syn2a, Shha, Mbp, Elavl3, Nestin and Ngn1 in early developmental stages of zebrafish. According to our results, it is possible that not only ATZ but also its metabolites (DACT, DIP and DE) have the same or even more toxic effects on different endpoints of the early developmental stages of zebrafish. PMID- 26803582 TI - The Correlation between Endoscopic Reflux Esophagitis and Combined Multichannel Intraluminal Impedance-pH Monitoring in Children. AB - BACKGROUND: Gastroesophageal reflux (GER) is the retrograde flow of gastric contents into the esophagus and may induce a variety of complications. Endoscopically visible breaks in the distal esophageal mucosa are the most reliable evidence of reflux esophagitis. Combined multichannel intraluminal impedance and pH-metry (MII-pH) is a technique that enables monitoring of GER independent of its acidity. The aim of this study is to investigate the GER patterns in children with the aid of MII-pH monitoring and determine the correlation between endoscopically proven reflux esophagitis and reflux types by MII-pH monitoring. METHODS: One hundred and twenty children were enrolled from January 2010 to October 2011 for MII-pH monitoring. We studied the GER patterns by means of pH (acid and nonacid reflux) and composition (liquid, mixed, and gas reflux) by the esophageal MII-pH signals. Meanwhile, 34 (28.3%) patients received esophagogastroduodenoscopy examination at the same time. The severity of reflux esophagitis was graded with Los Angeles classification. RESULTS: MII-pH monitoring significantly increased the detection of numbers of reflux compared with traditional 24-hour pH monitoring (p < 0.001). The significant cutoff value of MII-pH parameters including DeMeester score >= 21, duration of longest acid reflux >= 17 minutes, and occurrence of acid reflux for more than 5 minutes showed good correlation in the prediction of the presence of endoscopic reflux esophagitis. The odds ratios of the above mentioned parameters were 12.6, 8.94, and 7.5, respectively (p = 0.02, p = 0.01, and p = 0.01). Furthermore, >= 3 episodes per day of acid reflux for more than 5 minutes can predict the occurrence of severe reflux esophagitis (odds ratio 12.78, p = 0.009). CONCLUSION: MII-pH monitoring not only raised the diagnostic yield in identifying GER, but it also showed significant correlation with the presence of endoscopically proven reflux esophagitis in children. PMID- 26803583 TI - Validation of the Lille's Apathy Rating Scale in Very Mild to Moderate Dementia. AB - OBJECTIVE: Apathy is one of the most common and disabling syndromes of dementia and presents at all stages of the disease. Comprehensive and structured methods to assess apathy in dementia are still needed. Lille's Apathy Rating Scale (LARS) has shown good psychometric properties for apathy evaluation in Parkinson disease but has not been validated in dementia. The aim of this study was to validate the LARS in a cohort of patients with very mild to moderate dementia. METHODS: 101 patients with cognitive impairment (Clinical Dementia Rating <= 2) and 50 healthy subjects were recruited. Patient diagnoses included 43 individuals with Alzheimer disease, 41 frontotemporal dementia, and 17 primary progressive aphasia. In addition to LARS, the following assessments were administered: Clinical Dementia Rating, Interview for Deterioration in Daily Living Activities in Dementia, Functional Activities Questionnaire, Frontal Behavioral Inventory, Neuropsychiatric Inventory (NPI), and Hamilton Depression Rating Scale. RESULTS: Internal consistency for LARS (Cronbach's alpha) was 0.940. Test-retest intraclass correlation coefficient (ICC) was 0.940 and inter-rater ICC was 0.987. The correlation among LARS and NPI apathy scores (concurrent validity) was 0.834. Receiver operating characteristic analysis estimated an area under the curve of 0.987. The optimal cutoff point was -10. Although total LARS score was influenced by the presence of depression, this disorder was independent with respect to apathy. CONCLUSION: LARS is reliable and valid for detecting and quantifying apathy in patients with dementia, even in very early stages of the disease. PMID- 26803584 TI - The Metabolic Syndrome Predicts Longitudinal Changes in Clock Drawing Test Performance in Older Nondemented Hypertensive Individuals. AB - OBJECTIVES: The present study evaluated the metabolic syndrome (MetS) as independent predictor of 1-year longitudinal changes in cognitive function. METHODS: 104 stroke- and dementia-free older hypertensive subjects were studied. MetS was defined by NCEP ATP-III criteria. Cognitive function was assessed by the Clock Drawing Test (CDT); 1-year changes in cognitive function were expressed as annual changes in CDT performance. Brain magnetic resonance imaging studies (1.5T) were performed. RESULTS: Participants with MetS exhibited greater cognitive decline than those without (-1.78 +/- 1.47 versus -0.74 +/- 1.44 CDT points, t = 3.348, df = 102, p < 0.001). MetS predicted cognitive decline (beta = -0.327, t = -3.059, df = 96, p = 0.003) independently of its components, age, baseline cognition, neuroimaging findings, blood pressure levels, and duration of hypertension. With the exception of systolic blood pressure, none of the individual components of MetS explained 1-year changes in CDT performance. CONCLUSIONS: MetS as an entity predicted accelerated 1-year decline in cognitive function, assessed by CDT, in a sample of older hypertensive subjects. PMID- 26803585 TI - Wen-Xin Decoction ameliorates vascular endothelium dysfunction via the PI3K/AKT/eNOS pathway in experimental atherosclerosis in rats. AB - BACKGROUND: Nitric oxide (NO) is the most powerful vasodilator that inhibits leukocyte adhesion, platelet aggregation, and vascular smooth muscle cell proliferation. However, excessive NO can cause lipid peroxidation and direct endothelial cell damage. Therefore, investigation of the role of NO in artherosclerosis development is important. Wen-Xin Decoction (WXD) has been shown to relieve myocardial ischemia reperfusion injury and prevent leukocyte adhesion and invasion; in addition, it can accelerate angiogenesis and prevent platelet activation and aggregation. In this study, we focused on the NO pathway to further clarify the protective effects of WXD on the vascular endothelium in rat models of artherosclerosis. METHODS: Wistar rats were randomly divided into a normal group (n = 10) and a model group (n = 75). Rat models of atherosclerosis were generated by intraperitoneal vitamin D3 (3 months) injections and administration of a high-fat diet (3 months with vitamin D3 and 2 months alone). The model rats were randomly divided into five groups (n = 15 each): model (saline), atorvastatin (4.8 mg/kg/d atorvastatin), high-dose WXD (9 g/kg/d), medium-dose WXD (4.5 g/kg/d), and low-dose WXD (2.25 g/kg/d) groups. Each group received continuous drug or saline administration (suspended liquid gavage) for 30 days, following which all animals were sacrificed. The ultrastructure and histopathological changes of vascular endothelial cells and the expression of PI3K/AKT/eNOS and iNOS in the thoracic aorta tissue were analyzed. RESULTS: WXD increased NO levels, modulated the NO/ET-1 ratio, and promoted repair of the injured vascular endothelium in a dose-dependent manner. At a high dose, WXD regulated the NO/ET-1 ratio as effectively as atorvastatin; furthermore, it increased NO levels within the physiological range to prevent endothelial damage caused by excessive NO expression. Real-time polymerase chain reaction and Western blot analysis showed that WXD significantly upregulated the mRNA and protein expressions of PI3K, AKT, and eNOS mRNA and significantly increased AKT and eNOS phosphorylation. CONCLUSIONS: Our results suggest that WXD protects and maintains the integrity of the vascular endothelium by activating the PI3K/AKT/eNOS pathway, decreasing iNOS expression, and promoting the release of physiological NO levels. PMID- 26803586 TI - Ready, aim, shoot: stem cell regulation of the shoot apical meristem. AB - Plant shoot meristems contain stem cells that are continuously renewed to replenish cells that exit and differentiate during lateral organ formation. Complex cell-to-cell signaling systems balance division and differentiation. These center on ligand-receptor networks, hormone pathways, and transcriptional regulators that function in an integrated manner. In this review, we aim to highlight new findings in shoot stem cell regulation across species. PMID- 26803587 TI - Management and prevention of acute bleedings in the head and neck area with interventional radiology. AB - BACKGROUND: The Interventional Neuroradiology is becoming more important in the interdisciplinary treatment of acute haemorrhages due to vascular erosion and vascular tumors in the head and neck area. The authors report on acute extracranial haemorrhage in emergency situations but also on preventive embolization of good vascularized tumors preoperatively and their outcome. METHODS: Retrospective analysis of 52 patients, who underwent an interdisciplinary approach of the ORL Department and the Interventional Neuroradiology over 5 1/2 years at the Department of Otorhinolaryngology, Klinikum Rechts der Isar, Technical University of Munich, Germany. Their outcome was analysed in terms of success of the embolization, blood loss, survival rate and treatment failures. RESULTS: 39/52 patients were treated for acute haemorrhage. Twenty-five of them attributable to vascular erosion in case of malignant tumors. Affected vessels were the common carotid artery as well as its internal and external parts with branches like the ascending pharyngeal, the facial and the superior thyroid artery. Altogether 27/52 patients were treated for malignant tumors, 25/52 were attributable to acute haemorrhage due to epistaxis, after tonsillectomy, benign tumors and bleeding attributable to inflammations. Treatment of all patients consisted either of an unsuccessful approach via exposure, package of the bleeding, electrocoagulation or surgical ligature followed by embolization or the primary treatment via interventional embolization/stenting. CONCLUSIONS: The common monitoring of patients at the ORL and interventional neuroradiology is an important alternative especially in the treatment of severe acute haemorrhage, following vascular erosion in malignant tumors or benign diseases. But also the preoperative embolization of good vascularized tumors must be taken into account to prevent severe blood loss or acute intraoperative bleeding. PMID- 26803588 TI - Association between human leukocyte antigen class II and pulmonary tuberculosis due to mycobacterium tuberculosis in Uganda. AB - BACKGROUND: Mycobacterium tuberculosis (Mtb) is reported to infect about a third of the world's population but only 10% are thought to develop active tuberculosis (TB) disease. Host immunity regulated by human leukocyte antigens (HLA) is an important determinant of the outcome of the disease. Here we investigate HLA class II gene polymorphisms in susceptibility to TB, and whether particular HLA class II alleles were associated with TB in Uganda. METHODS: HIV negative patients with pulmonary TB (n = 43) and genetically related healthy household controls (n = 42) were typed for their HLA II class alleles using polymerase chain reaction sequence specific primer amplification. RESULTS: The HLA DQB1*03:03 allele was significantly less frequent in patients compared to healthy controls (10% in controls versus 0% in patients, p = 0.003). After correction for multiple comparisons the difference remained significant (p = 0.018). CONCLUSIONS: Our results suggest that the HLA-DQB1*03:03 allele may be associated with resistance to TB. PMID- 26803589 TI - The effects of a low-carbohydrate diet on appetite: A randomized controlled trial. AB - BACKGROUND AND AIMS: The relationship between dietary macronutrient composition and appetite is controversial. We examined the effects of a year-long low carbohydrate diet compared to a low-fat diet on appetite-related hormones and self-reported change in appetite. METHODS AND RESULTS: A total of 148 adults with a body mass index 30-45 kg/m(2), who were free of diabetes, cardiovascular disease and chronic kidney disease at baseline were randomly assigned to either a low-carbohydrate diet (carbohydrate [excluding dietary fiber]<40 g/day; N = 75) or a low-fat diet (<30% energy from fat, <7% from saturated fat; N = 73). Participants in both groups attended individual and group dietary counseling sessions where they were provided the same behavioral curriculum and advised to maintain baseline levels of physical activity. Appetite and appetite-related hormones were measured at 0, 3, 6 and 12 months of intervention. At 12 months, mean changes (95% CI) in peptide YY were -34.8 pg/mL (-41.0 to -28.6) and in the low-carbohydrate group and -44.2 pg/mL (-50.4 to -38.0) in the low-fat group (net change: 9.54 pg/mL [0.6 to 18.2]; p = 0.036). Approximately 99% of dietary effects on peptide YY are explained by differences in dietary macronutrient content. There was no difference in change in ghrelin or self-reported change in appetite between the groups. CONCLUSIONS: A low-fat diet reduced peptide YY more than a low-carbohydrate diet. These findings suggest that satiety may be better preserved on a low-carbohydrate diet, as compared to a low fat diet. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00609271. PMID- 26803590 TI - B vitamin treatments modify the risk of myocardial infarction associated with a MTHFD1 polymorphism in patients with stable angina pectoris. AB - BACKGROUND: Methylenetetrahydrofolate dehydrogenase (MTHFD1) catalyzes three sequential reactions that metabolize derivatives of tetrahydrofolate (THF) in folate-dependent one-carbon metabolism. Impaired MTHFD1 flux has been linked to disturbed lipid metabolism and oxidative stress. However, limited information is available on its relation to the development of atherothrombotic cardiovascular disease. METHODS AND RESULTS: We explored the association between a MTHFD1 polymorphism (rs1076991 C > T) and acute myocardial infarction (AMI), and potential effect modifications by folic acid/B12 and/or vitamin B6 treatment in suspected stable angina pectoris patients (n = 2381) participating in the randomized Western Norway B Vitamin Intervention Trial (WENBIT). During the median follow-up of 4.9 years 204 participants (8.6%) suffered an AMI. After adjusting for established CVD risk factors, the MTHFD1 polymorphism was significantly associated with AMI (HR: 1.49; 95% CI, 1.23-1.81). A similar association was observed among patients allocated to treatment with vitamin B6 alone (HR: 1.53; 95% CI, 1.01-2.31), and an even stronger relationship was seen in patients treated with both vitamin B6 and folic acid/B12 (HR: 2.35; 95% CI, 1.55-3.57). However, no risk association between the MTHFD1 polymorphism and AMI was seen in patients treated with placebo (HR: 1.29; 95% CI, 0.86-1.93) or folic acid/B12 (1.17; 95% CI, 0.83-1.65). CONCLUSION: A common and functional MTHFD1 polymorphism is associated with increased risk of AMI, although the risk seems to be dependent on specific B vitamin treatment. Further studies are warranted to elucidate the possible mechanisms, also in order to explore potential effect modifications by nutritional factors. PMID- 26803592 TI - Glycated haemoglobin does not accurately predict average capillary glucose in non insulin-treated type 2 diabetes: The PRISMA study experience. PMID- 26803591 TI - Metabolic syndrome and 10-year cardiovascular disease incidence: The ATTICA study. AB - AIMS: To evaluate the influence of metabolic syndrome (MetS) as well as inflammatory and renal markers on cardiovascular disease (CVD) incidence. METHODS AND RESULTS: During 2001-2002, 1514 men and 1528 women (>18 y) without any clinical evidence of CVD or any other chronic disease, at baseline, living in greater Athens area, Greece, were enrolled. In 2011-2012, the 10-year follow-up was performed in 2583 participants (15% of the participants were lost to follow up). Incidence of fatal or non-fatal CVD was defined according to WHO-ICD-10 criteria. MetS was defined using three definitions, provided by the National Cholesterol Education Program Adult Treatment panel III (revised NCEP ATP III), the International Diabetes Federation (IDF) or the Harmonized definition. Furthermore, the contributory predictive role of C-reactive protein (CRP), inteleukin-6, uric acid and estimated glomerular filtration rate in the aforementioned models was evaluated. History of MetS-NCEP was positively associated with CVD, adjusting for potential confounding factors (OR:1.83, 95%CI:1.24-2.72). Not statistically significant associations with CVD incidence were observed when using the IDF or the Harmonized definition. Additionally, none of the added inflammatory and renal function markers mediated the influence of MetS on CVD incidence (all p's from Sobel test >0.40). C-statistic values for the MetS definitions used exceeded 0.789 (CI:0.751-0.827), indicating fair-to-good predictive probability of the models. CONCLUSION: Results of the present work revealed the negative impact of MetS-NCEP, but not of the other MetS definitions, on CVD incidence, a key-point that may help in better understanding the role of IDF and Harmonized MetS definitions on CVD. PMID- 26803593 TI - Biomarkers and prediction of myocardial triglyceride content in non-diabetic men. AB - BACKGROUND AND AIMS: Lipid oversupply to cardiomyocytes or decreased utilization of lipids leads to cardiac steatosis. We aimed to examine the role of different circulating metabolic biomarkers as predictors of myocardial triglyceride (TG) content in non-diabetic men. METHODS AND RESULTS: Myocardial and hepatic TG contents were measured with 1.5 T magnetic resonance (MR) spectroscopy, and LV function, visceral adipose tissue (VAT), abdominal subcutaneous tissue (SAT), epicardial and pericardial fat by MR imaging in 76 non-diabetic men. Serum concentration of circulating metabolic biomarkers [adiponectin, leptin, adipocyte fatty acid binding protein 4 (A-FABP 4), resistin, and lipocalin-2] including beta-hydroxybuturate (beta-OHB) were measured. Subjects were stratified by tertiles of myocardial TG into low, moderate, and high myocardial TG content groups. Concentrations of beta-OHB were lower (p = 0.003) and serum levels of A FABP 4 were higher (p < 0.001) in the group with high myocardial TG content compared with the group with low myocardial TG content. beta-OHB was negatively correlated with myocardial TG content (r = -0.316, p = 0.006), whereas A-FABP 4 was not correlated with myocardial TG content (r = 0.192, p = 0.103). In multivariable analyses beta-OHB and plasma glucose levels were the best predictors of myocardial TG content independently of VAT and hepatic TG content. The model explained 58.8% of the variance in myocardial TG content. CONCLUSION: Our data showed that beta-OHB and fasting glucose were the best predictors of myocardial TG content in non-diabetic men. These data suggest that hyperglycemia and alterations in lipid oxidation may be associated with cardiac steatosis in humans. PMID- 26803594 TI - Lifestyle may modify the glucose-raising effect of genetic loci. A study in the Greek population. AB - BACKGROUND AND AIMS: Lifestyle habits including dietary intake and physical activity are closely associated with multiple body processes including glucose metabolism and are known to affect human health. Recent genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with glucose levels. The hypothesis tested here is whether a healthy lifestyle assessed via a score is associated with glycaemic traits and whether there is an interaction between the lifestyle and known glucose-raising genetic variants in association with glycaemic traits. METHODS AND RESULTS: Participants of Greek descent from the THISEAS study were included in this analysis. We developed a glucose preventive score (GPS) including dietary and physical activity characteristics. We also modelled a weighted genetic risk score (wGRS), based on 20 known glucose-raising loci, in order to investigate the impact of lifestyle gene interaction on glucose levels. The GPS was observed to be significantly associated with lower glucose concentrations (beta +/- SE: -0.083 +/- 0.021 mmol/L, P = 1.6 * 10(-04)) and the wGRS, as expected, with increased glucose levels (beta +/- SE: 0.020 +/- 0.007 mmol/L, P = 8.4 * 10(-3)). The association of the wGRS with glucose levels was attenuated after interaction with the GPS. A higher GPS indicated decreasing glucose levels in the presence of an increasing wGRS (beta interaction +/- SE: -0.019 +/- 0.007 mmol/L, P = 0.014). CONCLUSION: Our results indicate that lower glucose levels underlie a healthier lifestyle and also support an interaction between the wGRS for known glycaemic loci and GPS associated with lower glucose levels. These scores could be useful tools for monitoring glucose metabolism. PMID- 26803595 TI - Circulating CD36+ microparticles are not altered by docosahexaenoic or eicosapentaenoic acid supplementation. AB - BACKGROUND AND AIMS: Circulating microparticles (MP) are the source of a plasma derived form of the scavenger receptor CD36, termed soluble (s)CD36, the levels of which correlate with markers of atherosclerosis and risk of cardiovascular disease. Long chain n-3 polyunsaturated fatty acids have cardioprotective effects that we have previously reported to be gender specific. The aim of this study was to determine if dietary docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) supplementation affect circulating CD36 + MP levels, and if this occurs differentially in healthy men and women. METHODS AND RESULTS: Participants (43M, 51F) aged 39.6 +/- 1.7 years received 4 weeks of daily supplementation with DHA rich (200 mg EPA; 1000 mg DHA), EPA rich (1000 mg EPA; 200 mg DHA), or placebo (sunola) oil in a double-blinded, randomised, placebo controlled trial. Plasma CD36 + MP were enumerated by flow cytometry and differences between genders and treatments were evaluated by Student's or paired t-test and one way ANOVA. Males and females had similar levels of CD36 + MP at baseline (mean = 1018 +/- 325 vs 980 +/- 318; p = 0.577) and these were not significantly changed after DHA (M, p = 0.571; F, p = 0.444) or EPA (M, p = 0.361; F, p = 0.901) supplementation. Likewise, the overall percent change in these levels were not different between supplemented cohorts compared to placebo when all participants were combined (% change in CD36 + MP: DHA = 5.7 +/- 37.5, EPA = -3.4 +/- 35.4, placebo = -11.5 +/- 32.9; p = 0.158) or stratified by gender (M, DHA = -2.6 +/- 30.6, EPA = -15.1 +/- 20.1, placebo = -21.4 +/- 28.7, p = 0.187; F, DHA = 11.7 +/- 41.5, EPA = 6.8 +/- 42.9, placebo = -2.8 +/- 34.7, p = 0.552). CONCLUSION: The cardioprotective effects of DHA and EPA do not act through a CD36 + MP mechanism. PMID- 26803598 TI - Identifying beliefs underlying pre-drivers' intentions to take risks: An application of the Theory of Planned Behaviour. AB - Novice motorists are at high crash risk during the first few months of driving. Risky behaviours such as speeding and driving while distracted are well documented contributors to crash risk during this period. To reduce this public health burden, effective road safety interventions need to target the pre-driving period. We use the Theory of Planned Behaviour (TPB) to identify the pre-driver beliefs underlying intentions to drive over the speed limit (N=77), and while over the legal alcohol limit (N=72), talking on a hand-held mobile phone (N=77) and feeling very tired (N=68). The TPB explained between 41% and 69% of the variance in intentions to perform these behaviours. Attitudes were strong predictors of intentions for all behaviours. Subjective norms and perceived behavioural control were significant, though weaker, independent predictors of speeding and mobile phone use. Behavioural beliefs underlying these attitudes could be separated into those reflecting perceived disadvantages (e.g., speeding increases my risk of crash) and advantages (e.g., speeding gives me a thrill). Interventions that can make these beliefs safer in pre-drivers may reduce crash risk once independent driving has begun. PMID- 26803597 TI - Reduced dietary intake of pro-inflammatory Toll-like receptor stimulants favourably modifies markers of cardiometabolic risk in healthy men. AB - BACKGROUND AND AIMS: Because pro-inflammatory stimulants of Toll-like receptor-2 and TLR4 (pathogen-associated molecular patterns, PAMPs), are abundant in some processed foods, we explored the effects of diets enriched or depleted in these molecules on markers of cardiometabolic risk in man. METHODS AND RESULTS: Adherence to a low PAMP diet for 7 days reduced LDL-cholesterol (-0.69 mM, P = 0.024) and abdominal circumference (-1.6 cm, P = 0.001) in 11 habitual consumers of high PAMP foodstuffs, and these markers, together with leukocyte counts (+14%, P = 0.017) increased significantly after 4 days consuming predominantly high PAMP foods. Change in LDL-cholesterol and leukocyte counts correlated well with change in frequency of intake of high PAMP foodstuffs per individual (r = 0.540, P = 0.0095 and r = 0.6551, P = 0.0009, respectively). In an independent group of 13 healthy men, leukocyte counts and expression of the activation marker CD11b on granulocytes and monocytes were significantly reduced after a fresh onion meal (P < 0.05), but these effects were reversed by a high PAMP equivalent meal. CONCLUSIONS: A low PAMP diet is associated with reduced levels of several cardiometabolic risk factors, while a high PAMP diet reverses these effects. These findings suggest a novel potential mechanistic explanation for the observed association between processed food consumption and risk of cardiometabolic diseases. The study is registered at clinicaltrials.org (reference NCT02430064). PMID- 26803596 TI - Higher pericardial adiposity is associated with prevalent diabetes: The Coronary Artery Risk Development in Young Adults study. AB - BACKGROUND AND AIMS: Pericardial adipose tissue (PAT) is located on both sides of the pericardium. We tested whether PAT was associated with prevalent diabetes at the year 25 exam of the Coronary Artery Risk Development in Young Adults (CARDIA) study. METHODS AND RESULTS: The CARDIA Year 25 exam (2010-2011) included complete data for all covariates on 3107 participants. Prevalent diabetes (n = 436) was defined as high fasting (>=126 mg/dl) or 2-h postload glucose (>=200 mg/dl) or HbA1c (>=6.5%) or use of diabetes medications. Volume of PAT was measured from computed tomographic scans. Logistic regression was performed to examine the relationship between quartiles of PAT and diabetes. In regression models adjusted for field center, sex, race, age, systolic blood pressure, total cholesterol, log triglycerides, and treatment with blood pressure and cholesterol lowering medication, PAT volume in the 4th quartile was significantly associated with diabetes status after adjustment for BMI (OR 2.57, 95% CI 1.66, 3.98) or visceral adipose tissue (OR 2.08, 95% CI 1.32, 3.29). PAT volume in the 2nd and 3rd quartiles was not significantly associated with diabetes status relative to the first quartile. CONCLUSIONS: Metabolically active pericardial adipose tissue is associated with prevalent diabetes only at higher volumes independent of overall obesity. PMID- 26803599 TI - [On the risks associated with the doses of radiation used in imaging studies]. PMID- 26803600 TI - Engineering NiO sensitive materials and its ultra-selective detection of benzaldehyde. AB - Ongoing interest in oxide semiconductor as components of gas sensing devices is motivated by environmental monitoring and intelligent control. NiO with different precursor solution were synthesized by aqueous chemical deposition and pyrolysis process. Here the method is quite facile, green and free of surfactant. Their morphology, crystal structure and chemical composition have been systemically characterized by various techniques. Interestingly, the microstructures of NiO can be engineered by different nickel salt (nitrate or chloride). These NiO based gas sensors showed substantially enhanced responses to benzaldehyde target analyte and exhibited fast response-recover feature. The observed gas sensing behavior is explained in terms of oxygen ionosorption mechanism. PMID- 26803601 TI - Electrospray synthesis and properties of hierarchically structured PLGA TIPS microspheres for use as controlled release technologies. AB - Microsphere-based controlled release technologies have been utilized for the long term delivery of proteins, peptides and antibiotics, although their synthesis poses substantial challenges owing to formulation complexities, lack of scalability, and cost. To address these shortcomings, we used the electrospray process as a reproducible, synthesis technique to manufacture highly porous (>94%) microspheres while maintaining control over particle structure and size. Here we report a successful formulation recipe used to generate spherical poly(lactic-co-glycolic) acid (PLGA) microspheres using the electrospray (ES) coupled with a novel thermally induced phase separation (TIPS) process with a tailored Liquid Nitrogen (LN2) collection scheme. We show how size, shape and porosity of resulting microspheres can be controlled by judiciously varying electrospray processing parameters and we demonstrate examples in which the particle size (and porosity) affect release kinetics. The effect of electrospray treatment on the particles and their physicochemical properties are characterized by scanning electron microscopy, confocal Raman microscopy, thermogravimetric analysis and mercury intrusion porosimetry. The microspheres manufactured here have successfully demonstrated long-term delivery (i.e. 1week) of an active agent, enabling sustained release of a dye with minimal physical degradation and have verified the potential of scalable electrospray technologies for an innovative TIPS-based microsphere production protocol. PMID- 26803602 TI - Adsorption of Rhodamine B on two novel polar-modified post-cross-linked resins: Equilibrium and kinetics. AB - We employed two polar monomers, triallyl isocyanurate (TAIC) and butyl acrylate (BA), to copolymerize with divinylbenzene (DVB), and synthesized two starting copolymers labeled PDT and PDB. Then, the Friedel-Crafts alkylation reaction was performed for the two starting copolymers, and the residual pendent vinyl groups were consumed, and hence we obtained two novel polar-modified post-cross-linked resins PDTpc and PDBpc. The surface polarity greatly improved due to introduction of the polar monomers, and the Brunauer-Emmett-Teller (BET) surface area and pore volume significantly increased after the Friedel-Crafts alkylation reaction. Compared with the starting copolymers, the non-polar post-cross-linked resin PDVBpc and some other adsorbents in the references, PDTpc and PDBpc possessed a much enhanced adsorption to Rhodamine B, and the equilibrium capacity reached 578.2mg/g and 328.7mg/g, respectively, at an equilibrium concentration of 100mg/L, and the Freundlich model characterized the equilibrium data very well. The adsorption was a fast process and the kinetic data obeyed the micropore diffusion model. These results confirmed that PDTpc and PDBpc had the potential superiority in adsorptive removal of Rhodamine B from aqueous solution. PMID- 26803603 TI - pKa determination of graphene-like materials: Validating chemical functionalization. AB - We report a novel pKa determination for different graphene-like samples: graphene oxide (GO), reduced GO (rGO), graphene nanoribbons (GNR), oxidized GNR (GONR), thiol- and imidazole-functionalized GO (GOSH and GOIMZ, respectively) and thiol functionalized GONR (GONRSH). Using the specialized computational program BEST7 for treating titration curves, pKas for different functional groups were discriminated (confirmed by infrared spectra) and their composition quantified. Overall, three equilibria were distinguished, two relative to carboxylic acids exhibiting different acidic degrees (pKa1~4.0 and pKa2~6.0) and one relative to alcohols (pKa4~10.0). Upon functionalization on carboxylate sites, thiol (pKa(GOSH/GONRSH)=6.7) and imidazole (pKa(GOIMZ)=6.6) moieties were discerned, followed by a decrease of their carboxylate percentage (compared to the precursors), thus allowing determining the degree of functionalization (48% and 36% of thiol content for GOSH and GONRSH respectively, and 29% of imidazole for GOIMZ). The proposed method is innovative and simpler when compared to the traditional tools usually employed to quantify chemical functionalization. PMID- 26803604 TI - Mesoporous silica nanoparticles with controllable morphology prepared from oil-in water emulsions. AB - Mesoporous silica nanoparticles are an important class of materials with a wide range of applications. This paper presents a simple protocol for synthesis of particles as small as 40nm and with a pore size that can be as large as 9nm. Reaction conditions including type of surfactant, type of catalyst and presence of organic polymer were investigated in order to optimize the synthesis. An important aim of the work was to understand the mechanism behind the formation of these unusual structures and an explanation based on silica condensation in the small aqueous microemulsion droplets that are present inside the drops of an oil in-water emulsion is put forward. PMID- 26803605 TI - Enhanced chemiluminescence-based detection on gold substrate after electrografting of diazonium precursor-coated gold nanoparticles. AB - Since it was demonstrated that nanostructured surfaces are more efficient for the detection based on the specific capture of analytes, there is a real need to develop strategies for grafting nanoparticles onto flat surfaces. Among the different routes for the functionalization of a surface, the reduction of diazonium salts appears very attractive for the covalent immobilization of nanoparticles because this method does not require a pre-treatment of the surface. For achieving this goal, gold nanoparticles coated by precursor of diazonium salts were synthesized by reduction of gold salt in presence of mercaptoaniline. These mercaptoaniline-coated gold nanoparticles (Au@MA) were successfully immobilized onto various conducting substrates (indium tin oxide (ITO), glassy carbon (GC) and gold electrodes with flat terraces) after addition of sodium nitrite at fixed potential. When applied onto the gold electrodes, such a grafting strategy led to an obvious enhancement of the luminescence of luminol used for the biodetection. PMID- 26803606 TI - Beta-amyloid and phosphorylated tau metabolism changes in narcolepsy over time. AB - PURPOSE: The aim od this study is to test whether metabolism of beta-amyloid and tau proteins changes in narcolepsy along with the disease course. METHODS: We analyzed a population of narcoleptic drug-naive patients compared to a sample of healthy controls. Patients and controls underwent lumbar puncture for assessment of cerebrospinal fluid (CSF) beta-amyloid1-42 (Abeta42), total tau (t-tau), and phosphorylated tau (p-tau) levels. Moreover, based on the median disease duration of the whole narcolepsy group, the patients were divided into two subgroups: patients with a short disease duration (SdN, <5 years) and patients with a long disease duration (LdN, >5 years). RESULTS: We found significantly lower CSF Abeta42 levels in the whole narcolepsy group with respect to controls. Taking into account the patient subgroups, we documented reduced CSF Abeta42 levels in SdN compared to both LdN and controls. Even LdN patients showed lower CSF Abeta42 levels with respect to controls. Moreover, we documented higher CSF p-tau levels in LdN patients compared to both SdN and controls. Finally, a significant positive correlation between CSF Abeta42 levels and disease duration was evident. CONCLUSIONS: We hypothesize that beta-amyloid metabolism and cascade may be impaired in narcolepsy not only at the onset but also along with the disease course, although they show a compensatory profile over time. Concurrently, also CSF biomarkers indicative of neural structure (p-tau) appear to be altered in narcolepsy patients with a long disease duration. However, the mechanism underlying beta-amyloid and tau metabolism impairment in narcolepsy remains still unclear and deserves to be better elucidated. PMID- 26803607 TI - Ontogenetic effects on gazing behaviour: a case study of kennel dogs (Labrador Retrievers) in the impossible task paradigm. AB - Life experiences and living conditions can influence the problem-solving strategies and the communicative abilities of dogs with humans. The goals of this study were to determine any behavioural differences between Labrador Retrievers living in a kennel and those living in a house as pets and to assess whether kennel dogs show preferences in social behaviours for their caretaker relative to a stranger when they are faced with an unsolvable task. Nine Labrador Retrievers living in a kennel from birth and ten Labrador Retrievers living in a family as pets were tested. The experimental procedure consisted of three "solvable" tasks in which the dogs could easily retrieve food from a container followed by an "unsolvable" task in which the container was hermetically locked. Dogs of both groups spent the same amount of time interacting with the experimental apparatus. Kennel dogs gazed towards people for less time and with higher latency than pet dogs; however, there were no significant preferences in gazing towards the stranger versus the caretaker in both groups. These findings demonstrated that kennel dogs are less prone to use human-directed gazing behaviour when they are faced with an unsolvable problem, taking the humans into account to solve a task less than do the pet dogs. PMID- 26803608 TI - Conversion of a failed hip resurfacing arthroplasty to total hip arthroplasty: pearls and pitfalls. AB - Surface replacement arthroplasty (SRA) remains a viable alternative to total hip arthroplasty (THA) in appropriately selected, active adults with degenerative hip disease. However, orthopedic surgeons are facing a number of scenarios where revision of one or both components of an SRA is indicated. Indications for revision vary and impact the potential outcomes of conversion of a SRA to THA. While clinical outcomes are generally favorable, a growing body of data illustrates patients who undergo conversion of a SRA to THA to be at increased risk of requiring a repeat revision surgery and experiencing functional outcomes inferior to that of a primary THA. The results of patients undergoing conversion of a SRA to THA highlight the need for careful patient selection, thorough preoperative counseling, and technical precision when performing a SRA. Furthermore, a systematic approach to the failed SRA is necessary to ensure optimal clinical results. PMID- 26803609 TI - Expanding roles for reverse shoulder arthroplasty. AB - Since its introduction in the USA in 2003, reverse total shoulder arthroplasty (RTSA) has been used with increasingly frequency as surgeons have observed the remarkable improvement in pain, range of motion, and function associated with this implant. RTSA was initially used exclusively for elderly, low demand individuals with end-stage rotator cuff tear arthropathy. However, RTSA is now being increasingly successfully employed for the management of irreparable rotator cuff tears, glenohumeral osteoarthritis with an intact rotator cuff, acute proximal humerus fractures, the sequelae of proximal humerus fractures, neoplasms of the proximal humerus, inflammatory arthropathy, young patients and failed anatomic total shoulder arthroplasty and hemiarthroplasty. While long-term outcomes are pending, short- and mid-term follow-up results suggest that in experienced hands, RTSA may be a reasonable treatment for many previously difficult to treat pathologies within the shoulder. PMID- 26803610 TI - The arthritic glenoid: anatomy and arthroplasty designs. AB - The number of shoulder arthroplasty procedures has increased dramatically in recent years, with the primary indication being osteoarthritis (OA). Thus, morphology and subchondral bone changes associated with OA may be important factors to consider when choosing a replacement component. For surgical treatment, many implant options exist and survivability is often dependent on patient age, activity level, and progression of OA. In the placement of these replacement components, patient-specific guides now exist to improve component positioning, with the goal to improve long-term survivability by ensuring that intra-operative placement meets component design. PMID- 26803611 TI - Improvement of a predictive model in ovarian cancer patients submitted to platinum-based chemotherapy: implications of a GST activity profile. AB - PURPOSE: The success of chemotherapy in ovarian cancer (OC) is directly associated with the broad variability in platinum response, with implications in patients survival. This heterogeneous response might result from inter-individual variations in the platinum-detoxification pathway due to the expression of glutathione-S-transferase (GST) enzymes. We hypothesized that GSTM1 and GSTT1 polymorphisms might have an impact as prognostic and predictive determinants for OC. METHODS: We conducted a hospital-based study in a cohort of OC patients submitted to platinum-based chemotherapy. GSTM1 and GSTT1 genotypes were determined by multiplex PCR. RESULTS: GSTM1-null genotype patients presented a significantly longer 5-year survival and an improved time to progression when compared with GSTM1-wt genotype patients (log-rank test, P = 0.001 and P = 0.013, respectively). Multivariate Cox regression analysis indicates that the inclusion of genetic information regarding GSTM1 polymorphism increased the predictive ability of risk of death after OC platinum-based chemotherapy (c-index from 0.712 to 0.833). Namely, residual disease (HR, 4.90; P = 0.016) and GSTM1-wt genotype emerged as more important predictors of risk of death (HR, 2.29; P = 0.039; P = 0.036 after bootstrap). No similar effect on survival was observed regarding GSTT1 polymorphism, and there were no statistically significant differences between GSTM1 and GSTT1 genotypes and the assessed patients' clinical pathological characteristics. CONCLUSION: GSTM1 polymorphism seems to have an impact in OC prognosis as it predicts a better response to platinum-based chemotherapy and hence an improved survival. The characterization of the GSTM1 genetic profile might be a useful molecular tool and a putative genetic marker for OC clinical outcome. PMID- 26803612 TI - A simple indicator for non-destructive estimation of the violaxanthin cycle pigment content in leaves. AB - The photosynthetic apparatus of higher plants acclimates to irradiance. Among the features which are changing is the pool size of the pigments belonging to the violaxanthin cycle, in which zeaxanthin is formed. In high light grown leaves, the violaxanthin cycle pool size is up to five times larger than in low light. The changes are reversible on a time scale of several days. Since it has been published that violaxanthin cycle pigments do not transfer absorbed energy to chlorophyll, we hypothesized that excitation of chlorophyll fluorescence in the blue spectral region may be reduced in high light-acclimated leaves. Fluorescence excitation spectra of leaves of the Arabidopsis thaliana tt3 mutant showed strong differences between high and low light-acclimated plants from 430 to 520 nm. The resulting difference spectrum was similar to carotenoids but shifted by about 20 nm to higher wavelengths. A good correlation was observed between the fluorescence excitation ratio F 470/F 660 and the violaxanthin cycle pool size when leaves were acclimated to a range of irradiances. In parallel to the decline of F 470/F 660 with high light acclimation also the quantum yield of photosynthetic oxygen evolution in blue light decreased. The data confirm that violaxanthin cycle carotenoids do not transfer absorbed light to chlorophyll. It is proposed to use the ratio F 470/F 660 as an indicator for the light acclimation status of the chloroplasts in a leaf. PMID- 26803613 TI - Increasing Belief in the Effectiveness of HIV Treatment as Prevention: Results of Repeated, National Surveys of Australian Gay and Bisexual Men, 2013-15. AB - We surveyed Australian gay and bisexual men, assessing belief in HIV treatment as prevention (TasP) and support for early treatment. We identified the characteristics of participants who believed in TasP and supported early treatment using multivariate logistic regression. In 2013, 1316 men participated; 1251 participated in 2015. Belief in TasP increased from 2.6 % in 2013 to 13.1 % in 2015 (p < 0.001). The increase was most noticeable among HIV-positive men (from 9.7 % to 46.2 %). Support for early treatment increased from 71.8 % to 75.3 % (p = 0.02). Belief in TasP was associated with being HIV-positive, having a tertiary education, having recent condomless anal intercourse with casual male partners, and ever having taken post-exposure prophylaxis. Support for early HIV treatment was associated with being younger, living in New South Wales and being in paid employment. We recommend continued monitoring of the growing gap in belief about TasP between HIV-positive men and HIV-negative/untested men. PMID- 26803614 TI - Influence of DAOA and RGS4 genes on the risk for psychotic disorders and their associated executive dysfunctions: A family-based study. AB - BACKGROUND: Glutamatergic neurotransmission dysfunction has classically been related to the aetiology of psychotic disorders. A substantial polygenic component shared across these disorders has been reported and molecular genetics studies have associated glutamatergic-related genes, such as d-amino acid oxidase activator (DAOA) and regulator of G-protein signalling 4 (RGS4) with the risk for psychotic disorders. Our aims were to examine: (i) the relationship between DAOA and RGS4 and the risk for psychotic disorders using a family-based association approach, and (ii) whether variations in these genes are associated with differences in patients' cognitive performance. METHODS: The sample comprised 753 subjects (222 patients with psychotic disorders and 531 first-degree relatives). Six SNPs in DAOA and 5 SNPs in RGS4 were genotyped. Executive cognitive performance was assessed with Trail Making Test B (TMT-B) and Wisconsin Card Sorting Test (WCST). Genetic association analyses were conducted with PLINK, using the transmission disequilibrium test (TDT) for the family-based study and linear regression for cognitive performance analyses. RESULTS: The haplotype GAGACT at DAOA was under-transmitted to patients (P=0.0008), indicating its association with these disorders. With regards to cognitive performance, the DAOA haplotype GAGGCT was associated with worse scores in TMT-B (P=0.018) in SZ patients only. RGS4 analyses did not report significant results. CONCLUSIONS: Our findings suggest that the DAOA gene may contribute to the risk for psychotic disorders and that this gene may play a role as a modulator of executive function, probably through the dysregulation of the glutamatergic signalling. PMID- 26803615 TI - A cluster-analytical approach toward real-world outcome in outpatients with stable schizophrenia. AB - BACKGROUND: This study aims to empirically identify profiles of functioning, and the correlates of those profiles in a sample of patients with stable schizophrenia in a real-world setting. The second aim was to assess factors associated with best profile membership. METHODS: Three hundred and twenty-three outpatients were enrolled in a cross-sectional study. A two-step cluster analysis was used to define groups of patients by using baseline values for the Heinrichs Carpenter Quality of Life Scale (QLS) total score. Logistic regression was used to construct models of class membership. RESULTS: Our study identified three distinct clusters: 50.4% of patients were classified in the "moderate" cluster, 27.9% in the "poor" cluster, 21.7% in the "good" cluster. Membership in the "good" cluster versus the "poor" cluster was characterized by less severe negative (OR=.832) and depressive symptoms (OR=.848), being employed (OR=2.414), having a long-term relationship (OR=.256), and treatment with second-generation antipsychotics (SGAs) (OR=3.831). Nagelkerke R(2) for this model was .777. CONCLUSIONS: Understanding which factors are associated with better outcomes may direct specific and additional therapeutic interventions, such as treatment with SGAs and supported employment, in order to enhance benefits for patients, as well as to improve the delivery of care in the community. PMID- 26803616 TI - Relationship between body mass index and depression in women: A 7-year prospective cohort study. The APNA study. AB - BACKGROUND: The association between body mass index (BMI) and depression is complex and controversial. The present study examined the relationship between BMI and new-onset depression during 7 years of follow-up in 20,212 adult women attending Primary Health Care Centres in Navarra, Spain. METHODS: The Atencion Primaria de Navarra (APNA) study is a dynamic prospective cohort study. A total of 20,212 women aged 18-99 years (mean age: 50.7 +/- 18.5 years) without depression at baseline were selected from 2004 to 2011. We estimated the incidence of depression. We used the Kaplan-Meier analysis to predict the survival curve. The risk of depression onset according to different measures of BMI at baseline was assessed using Cox regression analyses. RESULTS: During the 7 years of follow-up, depression appeared in 8.9% (95% CI 8.5-9.3). The highest rates of depression incidence at follow-up occurred in underweight and obese women (9.8% [95% CI 7.3-12.9] and 10.3% [95% CI 9.5-11.1] respectively). The distribution of depression incidence by weight category was U-shaped. The risk of depression increased over time with an observed Kaplan-Meier estimation of 6.67. After adjusting for age, underweight and obese women at baseline have increased risk of depression onset during the follow-up period compared with normal weight women (HR=1.48, 95% CI=1.09-2.00 and HR=1.14, 95% CI=1.01-1.29 respectively). CONCLUSIONS: In this 7-year prospective study in the APNA women population, depression emerged in 8.9%. Being underweight or obese (not overweight) at baseline is significantly associated with future onset of depression. PMID- 26803617 TI - Exome sequencing identifies a nonsense mutation in Fam46a associated with bone abnormalities in a new mouse model for skeletal dysplasia. AB - We performed exome sequencing for mutation discovery of an ENU (N-ethyl-N nitrosourea)-derived mouse model characterized by significant elevated plasma alkaline phosphatase (ALP) activities in female and male mutant mice, originally named BAP014 (bone screen alkaline phosphatase #14). We identified a novel loss of-function mutation within the Fam46a (family with sequence similarity 46, member A) gene (NM_001160378.1:c.469G>T, NP_001153850.1:p.Glu157*). Heterozygous mice of this mouse line (renamed Fam46a (E157*Mhda)) had significantly high ALP activities and apparently no other differences in morphology compared to wild type mice. In contrast, homozygous Fam46a (E157*Mhda) mice showed severe morphological and skeletal abnormalities including short stature along with limb, rib, pelvis, and skull deformities with minimal trabecular bone and reduced cortical bone thickness in long bones. ALP activities of homozygous mutants were almost two-fold higher than in heterozygous mice. Fam46a is weakly expressed in most adult and embryonic tissues with a strong expression in mineralized tissues as calvaria and femur. The FAM46A protein is computationally predicted as a new member of the superfamily of nucleotidyltransferase fold proteins, but little is known about its function. Fam46a (E157*Mhda) mice are the first mouse model for a mutation within the Fam46a gene. PMID- 26803618 TI - Effect of Nano-HA/Collagen Composite Hydrogels on Osteogenic Behavior of Mesenchymal Stromal Cells. AB - This study aimed to comparatively evaluate the in vitro effect of nanosized hydroxyapatite and collagen (nHA/COL) based composite hydrogels (with different ratios of nHA and COL) on the behavior of human mesenchymal stromal cells (MSCs), isolated from either adipose tissue (AT-MSCs) or bone marrow (BM-MSCs). We hypothesized that (i) nHA/COL composite hydrogels would promote the osteogenic differentiation of MSCs in an nHA concentration dependent manner, and that (ii) AT-MSCs would show higher osteogenic potential compared to BM-MSCs, due to their earlier observed higher proliferation and osteogenic differentiation potential in 2D in vitro cultures [1]. The obtained results indicated that AT-MSCs show indeed high proliferation, differentiation and mineralization capacities in nHA/COL constructs compared to BM-MSCs, but this effect was irrespective of nHA concentration. Based on the results of alkaline phosphatase (ALP) activity and osteocalcin (OCN) protein level, the osteogenic differentiation of BM-MSCs started in the beginning of the culture period and for AT-MSCs at the end of the culture period. At a molecular level, both cell types showed high expression of osteogenic markers (bone morphogenic protein 2 [BMP2], runt-related transcription factor 2 [RUNX2], OCN or COL1) in both an nHA concentration and time dependent manner. In conclusion, AT-MSCs demonstrated higher osteogenic potential in nHA/COL based 3D micro-environments compared to BM-MSCs, in which proliferation and osteogenic differentiation were highly promoted in a time dependent manner, irrespective of nHA amount in the constructs. The fact that AT-MSCs showed high proliferation and mineralization potential is appealing for their application in future pre-clinical research as an alternative cell source for BM-MSCs. PMID- 26803619 TI - Toll-Like Receptors: Ligands, Cell-Based Models, and Readouts for Receptor Action. AB - This chapter details Toll-like receptors (TLRs) and the tools available to study their biology in vitro. Key parameters to consider before exploring TLR action such as receptor localization, signaling pathways, nature of ligands and cellular expression are introduced. Cellular models (i.e., host cells and readouts) based on the use of cell lines, primary cells, or whole blood are presented. The use of modified TLRs to circumvent some technical problems is also discussed. PMID- 26803620 TI - Bioinformatic Analysis of Toll-Like Receptor Sequences and Structures. AB - Continual advancements in computing power and sophistication, coupled with rapid increases in protein sequence and structural information, have made bioinformatic tools an invaluable resource for the molecular and structural biologist. With the degree of sequence information continuing to expand at an almost exponential rate, it is essential that scientists today have a basic understanding of how to utilise, manipulate and analyse this information for the benefit of their own experiments. In the context of Toll-Interleukin I Receptor domain containing proteins, we describe here a series of the more common and user-friendly bioinformatic tools available as Internet-based resources. These will enable the identification and alignment of protein sequences; the identification of functional motifs; the characterisation of protein secondary structure; the identification of protein structural folds and distantly homologous proteins; and the validation of the structural geometry of modelled protein structures. PMID- 26803621 TI - Toll-Like Receptor Interactions Measured by Microscopic and Flow Cytometric FRET. AB - Protein-protein interactions regulate biological networks. The most proximal events that initiate signal transduction frequently are receptor dimerization or conformational changes in receptor complexes. Toll-like receptors (TLRs) are transmembrane receptors that are activated by a number of exogenous and endogenous ligands. Most TLRs can respond to multiple ligands and the different TLRs recognize structurally diverse molecules ranging from proteins, sugars, lipids, and nucleic acids. TLRs can be expressed on the plasma membrane or in endosomal compartments and ligand recognition thus proceeds in different microenvironments. Not surprisingly, distinctive mechanisms of TLR receptor activation have evolved. A detailed understanding of the mechanisms of TLR activation is important for the development of novel synthetic TLR activators or pharmacological inhibitors of TLRs. Confocal laser scanning microscopy combined with GFP technology allows the direct visualization of TLR expression in living cells. Fluorescence resonance energy transfer (FRET) measurements between two differentially tagged proteins permit the study of TLR interaction, and distances between receptors in the range of molecular interactions can be measured and visualized. Additionally, FRET measurements combined with confocal microscopy provide detailed information about molecular interactions in different subcellular localizations. These techniques permit the dynamic visualization of early signaling events in living cells and can be utilized in pharmacological or genetic screens. PMID- 26803622 TI - Using Confocal Microscopy to Investigate Intracellular Trafficking of Toll-Like Receptors. AB - Toll-like receptors (TLR) survey the extracellular space, cytoplasm, and endosomal compartments for signs of infection or tissue injury. Over the past decade, it has become evident that TLR activation and signal transduction can be regulated by subcellular compartmentalization of both the receptors and their downstream signaling components. Immunofluorescence and/or overexpression of fluorescently "tagged"' proteins teamed with confocal microscopy presents a powerful technique for studying the spatial organization of TLRs, their signaling mediators, and the dynamic processes they activate. This chapter details the common methods for determining the subcellular location of TLRs in both live and fixed cells. PMID- 26803623 TI - Assessing the Inhibitory Activity of Oligonucleotides on TLR7 Sensing. AB - Aberrant sensing of self-nucleic acids by Toll-like receptor (TLR) 7, 8, or 9 is associated with several autoimmune disorders, including systemic lupus erythematosus (SLE), rheumatoid arthritis, psoriasis, or systemic sclerosis. In recent years, several classes of synthetic oligonucleotides have been shown to antagonize sensing of immunostimulatory nucleic acids by TLR7/8/9, indicating that these molecules could have therapeutic applications in such autoimmune diseases. Conversely, synthetic oligonucleotides used in therapeutic technologies such as antisense and microRNA inhibitors also have the potential to inhibit TLR7/8/9 sensing, rendering patients more susceptible to viral/bacterial infections. This chapter describes a protocol to define the inhibitory activity of synthetic oligonucleotides on TLR7. PMID- 26803624 TI - Methods for Delivering DNA to Intracellular Receptors. AB - Cytosolic DNA can indicate infection and induces type I interferon (IFN) and AIM2 inflammasome responses. Characterization of these responses has required introduction of DNA into the cytosol of macrophages by either chemical transfection or electroporation, each of which has advantages in different applications. We describe here optimized procedures for both electroporation and chemical transfection, including the centrifugation of chemical transfection reagent onto cells, which greatly increases the speed and strength of responses. Appropriate choice of DNA and use of these methods allow study of either the cytosolic DNA responses in isolation or the simultaneous stimulation of cytosolic receptors and the CpG DNA receptor toll-like receptor 9 (TLR9) in the endosomes. PMID- 26803625 TI - Detection of Interaction Between Toll-Like Receptors and Other Transmembrane Proteins by Co-immunoprecipitation Assay. AB - Toll-like receptors are type I membrane proteins and bind other membrane proteins often via a specific interaction between transmembrane domains. The co immunoprecipitation assay is a widely used biochemical technique for assessing interactions among proteins in cell lysates or tissue extracts. By isolating a native protein complex with a specific antibody against a protein of interest, followed by western blotting with an antibody for a binding partner, the co immunoprecipitation assay can be used to confirm a putative interaction between two proteins. The co-immunoprecipitation assay can also be combined with a proteomics approach such as protein mass spectrometry to build an interactome of a target protein. Despite its usefulness and popularity to probe protein interactions within complex biological samples, the co-immunoprecipitation assay of membrane proteins is rather tricky, often resulting in false data. Here, we describe a co-immunoprecipitation method for analyzing interactions between toll like receptors and other membrane proteins, using the interaction between TLR9 and UNC93B1 as an example. Especially, we describe an optimal cell lysis and sample preparation method to preserve protein interactions mediated by transmembrane domains. PMID- 26803626 TI - Flow Cytometry-Based Bead-Binding Assay for Measuring Receptor Ligand Specificity. AB - In this chapter we describe a fluorescent bead-binding assay, which is an efficient and feasible method to measure interaction between ligands and receptors on cells. In principle, any ligand can be coated on fluorescent beads either directly or via antibodies. Binding between ligand-coated beads and cells can be measured by flow cytometry, which results in an easily quantifiable readout. Furthermore, it allows measuring of binding by specific cell subsets within a mixed cell population. Overall, this method is a convenient and easily standardized assay for measuring binding. PMID- 26803627 TI - Measuring Monomer-to-Filament Transition of MAVS as an In Vitro Activity Assay for RIG-I-Like Receptors. AB - During viral infection, the innate immune RIG-I like receptors (RLRs) recognize viral double stranded RNA (dsRNA) and trigger filament assembly of the adaptor protein Mitochondrial Anti-viral Signaling protein (MAVS). The MAVS filament then activates anti-viral signaling events including the up-regulation of type I interferon expression. In recent years, much insight has been gained into how RLRs recognize dsRNA, but the precise mechanism of how activated RLRs stimulate MAVS filament formation remains less understood. In this chapter, we describe an in vitro reconstitution assay that we have previously developed to study the RLR catalyzed filament assembly of MAVS. We provide technical guidance for purifying the caspase activation recruitment domain (CARD) of MAVS (MAVS(CARD)) as a functional monomer and also preformed filament seed. We also describe the methods to monitor the monomer-to-filament transition of MAVS(CARD) upon stimulation. This protocol provides a minimalist approach to studying RLR signaling events and can potentially be applied to elucidate signaling mechanisms of other innate immune receptors, such as Toll-like receptors and inflammasomes, that involve higher order assemblies of CARDs or related domains for their downstream signal activation. PMID- 26803628 TI - Co-transcriptomic Analysis by RNA Sequencing to Simultaneously Measure Regulated Gene Expression in Host and Bacterial Pathogen. AB - Intramacrophage pathogens subvert antimicrobial defence pathways using various mechanisms, including the targeting of host TLR-mediated transcriptional responses. Conversely, TLR-inducible host defence mechanisms subject intramacrophage pathogens to stress, thus altering pathogen gene expression programs. Important biological insights can thus be gained through the analysis of gene expression changes in both the host and the pathogen during an infection. Traditionally, research methods have involved the use of qPCR, microarrays and/or RNA sequencing to identify transcriptional changes in either the host or the pathogen. Here we describe the application of RNA sequencing using samples obtained from in vitro infection assays to simultaneously quantify both host and bacterial pathogen gene expression changes, as well as general approaches that can be undertaken to interpret the RNA sequencing data that is generated. These methods can be used to provide insights into host TLR-regulated transcriptional responses to microbial challenge, as well as pathogen subversion mechanisms against such responses. PMID- 26803629 TI - Simple Methods to Investigate MicroRNA Induction in Response to Toll-Like Receptors. AB - In this chapter, we describe simple methods to investigate microRNA (miRNA) induction in response to lipopolysaccharide, the ligand for Toll-Like Receptor-4 activation. In brief, we demonstrate how to investigate global miRNA induction and/or repression in bone marrow-derived macrophages using TaqMan MicroRNA Arrays, followed by methods to measure individual miRNAs and target mRNA expression. Moreover, we explain step-by-step instructions on how to modulate endogenous miRNA expression through the use of miRNA inhibitors and mimics as well as highlight how miRNA modulation can be used to confirm mRNA targeting via Luciferase reporter assay. Moreover, these methods can be applied to whichever cell type and cellular function under investigation. PMID- 26803630 TI - Determining the Function of Long Noncoding RNA in Innate Immunity. AB - The advent of deep sequencing technologies has provided us with an unprecedented view of the human genome. Over 85 % of the genome is actively transcribed, yet we do not know the function of the vast majority of these RNA transcripts. Long noncoding RNAs (lncRNA) represent the largest group of RNA genes transcribed in the cell and currently there is limited experimental data supporting the functions of a very small proportion of these transcripts. lncRNA are expressed in a highly cell type specific manner and our interests involve understanding the role they play in innate immune signaling networks. In this chapter I will outline the approach we took to attempt to uncover the role for lncRNA in innate immune cells. Two of the main techniques required to study lncRNA are RNA-seq and loss of function analysis. This allows us to first identify all lncRNA in a cell type of choice and then try to determine the functional significance of these transcripts. This approach has been successful for us to date in identifying lincRNA-Cox2 as a highly inflammatory inducible lncRNA that is responsible for activation and repression of distinct immune genes. PMID- 26803631 TI - Analysis of Post-transcriptional Gene Regulation of Nod-Like Receptors via the 3'UTR. AB - Innate immune signaling is the front line of defense against pathogens, leading to an appropriate response of immune cells upon activation of their pattern recognition receptors (PRRs) by microbial products, such as Toll-like receptors (TLRs). Apart from transcriptional control, gene expression in the innate immune system is also highly regulated at the post-transcriptional level. miRNA or RNA binding protein can bind to the 3' untranslated region (UTR) of target mRNAs and affect their mRNA stability and translation efficiency, which ultimately affects the amount of protein that is produced. In recent years, a new group of PRRs, the Nod-like receptors (NLR) have been discovered. They often cooperate with TLR signaling to induce potent inflammatory responses. Many NLRs can form inflammasomes, which facilitate the production of the potent pro-inflammatory cytokine IL-1beta and other inflammatory mediators. In contrast to TLRs, the importance of post-transcriptional regulators in the context of inflammasomes has not been well defined. This chapter describes a series of experimental approaches to determine the effect of post-transcriptional regulation for a gene of interest using the best-studied NLR, NLRP3, as an example. To start investigating post transcriptional regulation, 3'UTR luciferase experiments can be performed to test if regulatory sequences in the 3'UTR are functional. An RNA pull-down approach followed by mass spectrometry provides an unbiased assay to identify RNA-binding proteins that target the 3'UTR. Candidate binding proteins can then be further validated by RNA immunoprecipitation (RNA-IP), where the candidate protein is isolated using a specific antibody and bound mRNAs are analyzed by qPCR. PMID- 26803632 TI - TLR Function in Murine CD4(+) T Lymphocytes and Their Role in Inflammation. AB - Toll-like receptor (TLR) signaling represents an evolutionary-conserved mechanism allowing for the rapid detection of broad molecular patterns that are common to different groups of pathogens. TLRs are traditionally associated with cells of the innate immune response where ligation of a TLR alone can lead to cellular activation and the initialization of an immune response. Cells of adaptive immunity, namely different classes of T and B lymphocytes, are also known to express a variety of TLRs. Conversely, the functional and signaling outcomes of TLRs are decidedly different in cells of the adaptive immune response. T lymphocytes generally have substantially lower TLR expression compared to innate cells, suggesting that TLRs function in a highly specialized capacity in this cell type. Certain TLRs act in a co-stimulatory capacity on T cells, amplifying activation only in the presence of simultaneous T-cell receptor engagement. However, the full array of TLR signaling events and outcomes in T lymphocytes remains poorly understood. Here, we describe a few methods for investigating the general function of TLRs on T lymphocytes in vitro and in vivo with an emphasis on the study of CD4(+) T cells. Most of these procedures can be adapted for the study of TLR signaling on other classes of lymphocytes as well. PMID- 26803633 TI - Analysis by Flow Cytometry of B-Cell Activation and Antibody Responses Induced by Toll-Like Receptors. AB - Toll-like receptors (TLRs) are expressed in B lymphocytes and contribute to B cell activation, antibody responses, and their maturation. TLR stimulation of mouse B cells induces class switch DNA recombination (CSR) to isotypes specified by cytokines, and also induces formation of IgM(+) as well as class-switched plasma cells. B-cell receptor (BCR) signaling, while on its own inducing limited B-cell proliferation and no CSR, can enhance CSR driven by TLRs. Particular synergistic or antagonistic interactions among TLR pathways, BCR, and cytokine signaling can have important consequences for B-cell activation, CSR, and plasma cell formation. This chapter outlines protocols for the induction and analysis of B-cell activation and antibody production by TLRs with or without other stimuli. PMID- 26803634 TI - Toll-Like Receptor-Dependent Immune Complex Activation of B Cells and Dendritic Cells. AB - High titers of autoantibodies reactive with DNA/RNA molecular complexes are characteristic of autoimmune disorders such as systemic lupus erythematosus (SLE). In vitro and in vivo studies have implicated the endosomal Toll-like receptor 9 (TLR9) and Toll-like receptor 7 (TLR7) in the activation of the corresponding autoantibody producing B cells. Importantly, TLR9/TLR7-deficiency results in the inability of autoreactive B cells to proliferate in response to DNA/RNA-associated autoantigens in vitro, and in marked changes in the autoantibody repertoire of autoimmune-prone mice. Uptake of DNA/RNA-associated autoantigen immune complexes (ICs) also leads to activation of dendritic cells (DCs) through TLR9 and TLR7. The initial studies from our lab involved ICs formed by a mixture of autoantibodies and cell debris released from dying cells in culture. To better understand the nature of the mammalian ligands that can effectively activate TLR7 and TLR9, we have developed a methodology for preparing ICs containing defined DNA fragments that recapitulate the immunostimulatory activity of the previous "black box" ICs. As the endosomal TLR7 and TLR9 function optimally from intracellular acidic compartments, we developed a facile methodology to monitor the trafficking of defined DNA ICs by flow cytometry and confocal microscopy. These reagents reveal an important role for nucleic acid sequence, even when the ligand is mammalian DNA and will help illuminate the role of IC trafficking in the response. PMID- 26803635 TI - Analysis of TLR-Induced Metabolic Changes in Dendritic Cells Using the Seahorse XF(e)96 Extracellular Flux Analyzer. AB - Engagement of Toll-like receptors (TLRs) on dendritic cells (DCs) triggers the expression of a large set of genes involved in DC activation and maturation, which allow them to act efficiently as antigen-presenting cells. Recently, it has become clear that TLR signalling in DCs also results in dramatic metabolic changes that are integral to their changed biology. Here, we describe a detailed protocol on how DC metabolism can be studied after TLR stimulation using the 96 well format Extracellular Flux (XF(e)96) Analyzer from Seahorse Bioscience, a machine that allows one to simultaneously assess rates of oxidative phosphorylation and glycolysis in real-time, in live cells and in a high throughput manner. PMID- 26803636 TI - Toll-Like Receptor Signalling and the Control of Intestinal Barrier Function. AB - Epithelial barrier function and innate immunity are fundamental to the pathogenesis of inflammatory and infectious disease. Along with plasma membranes, epithelial cells are the primary cellular determinant of epithelial barrier function. The mechanism by which polarized epithelia form a permeability barrier is of fundamental importance to the prevention of many infectious and inflammatory diseases. Moreover, epithelial cells express Toll-like receptors (TLRs) which upon recognition of conserved microbial factors such as lipopolysaccharide (LPS) induce epithelial responses including epithelial cell proliferation, secretion of secretory IgA into the lumen and production mucins and antimicrobial peptides, thereby promoting intestinal barrier function. Understanding gut barrier integrity and regulation of permeability is crucial to increase our understanding of the pathogenesis of intestinal disease. A variety of tests have been developed to assess this barrier, including assessing intestinal epithelial cell proliferation or death, intestinal tight junction status and the consequence of intestinal barrier integrity loss such as increased intestinal permeability and susceptibility to bacterial infection. Using a mouse model, this chapter describes some of the methods to assess the functional integrity of this epithelial barrier and the part played by a TLR signalling pathway. PMID- 26803637 TI - Understanding the Role of Cellular Molecular Clocks in Controlling the Innate Immune Response. AB - The importance of the 24-h daily cycle, termed circadian, on immune function has been highlighted by a number of recent studies. Immune parameters such as the response to bacterial challenge or immune cell trafficking change with time of day and disruption of circadian rhythms has been linked to inflammatory pathologies. We are beginning to uncover that the key proteins that comprise the molecular clock, most notably BMAL1, CLOCK, and REV-ERBalpha, also control fundamental aspects of the immune response. Given the ubiquitous nature of the molecular clock in controlling many other types of physiologies such as metabolism and cardiovascular function, a more thorough understanding of the daily rhythm of the immune system may provide important insight into aspects of patient care such as vaccinations and how we manage infectious and inflammatory diseases. In this chapter, we describe a series of experiments to look at circadian expression and function in immune cells. The experiments described herein may provide an initial assessment of the role of the molecular clock on an immune response from any cell type of interest. PMID- 26803638 TI - Methods to Investigate the Role of Toll-Like Receptors in Allergic Contact Dermatitis. AB - Allergic contact disease is a common inflammatory skin disease resulting from hyperresponsiveness to harmless nonprotein substances such as metals, fragrances, or rubber. Recent research has highlighted a prominent role of Toll-like receptors, particularly TLR4 in contact allergen-induced innate immune activation that crucially contributes to the pathogenesis of this disease. Here we describe several methods to investigate the role of Toll-like receptors in contact allergen-induced pro-inflammatory responses. These include expansion of disease relevant human primary cells including endothelial cells and keratinocytes and their manipulation of TLR signaling by transfection, retroviral infection and RNA interference, basic methods to induce contact hypersensitivity in mice, and protocols for adoptive transfer of hapten-stimulated dendritic cells and T cells from TLR-deficient mice to wild-type mice and vice versa wild-type mice to TLR deficient mice in order to explore cell-specific roles of TLRs in contact hypersensitivity responses. PMID- 26803639 TI - Allergens and Activation of the Toll-Like Receptor Response. AB - Pattern recognition receptors (PRRs) provide a crucial function in the detection of exogenous and endogenous danger signals. The Toll-like receptors (TLRs) were the first family of PRRs to be discovered and have been extensively studied since. Whilst TLRs remain the best characterized family of PRRs there is still much to be learnt about their mode of activation and the mechanisms of signal transduction they employ. Much of our understanding of these processes has been gathered through the use of cell based signaling assays utilizing specific gene reporters or cytokine secretion based readouts. More recently it has become apparent that the repertoire of ligands recognized by these receptors may be wider than originally assumed and that their activation may be sensitized, or at least modulated by the presence of common household allergens such as the cat dander protein Fel d 1, or the house dust mite allergen Der p 2. In this chapter we provide an overview of the cell culture and stimulation processes required to study TLR signaling in HEK293 based assays and in bone marrow-derived macrophages. PMID- 26803640 TI - Investigating the Role of Toll-Like Receptors in Models of Arthritis. AB - Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation leading to tissue destruction and progressive loss of joint function. Here we describe two methods that can be used to assess the contribution of toll-like receptors (TLRs), and their potential ligands, to RA pathogenesis. We focus on the antigen-induced model of murine arthritis and human synovial tissue explant models. Both enable detection of TLR, and TLR ligand, expression, as well as investigation of the effect of inhibition of these molecules. Each offers a unique insight into disease; with murine models allowing kinetic analysis in live animals and explant models allowing examination of inflamed human tissue, which together can help us to dissect the role of TLRs in the onset and progression of RA. PMID- 26803641 TI - Delineating the Role of Toll-Like Receptors in the Neuro-inflammation Model EAE. AB - Experimental autoimmune encephalomyelitis (EAE) is the most relevant and commonly used animal model to study autoimmune demyelinating diseases like Multiple Sclerosis (MS). In EAE, the activation of CD4+ T-cells is considered to be the main trigger leading to inflammation and central nervous system (CNS) demyelination. Toll-like receptors (TLRs) are the most important and first class of pattern recognition receptors (PRRs) in innate immune system and play critical roles in initiating inflammatory responses and promoting adaptive immune responses due to their ability to recognize a wide range of pathogen associated molecular patterns (PAMPs) and being expressed in a wide range of cell types both in the innate and adaptive immune systems. Upon TLR stimulation by appropriate ligand, innate immune cells produce pro-inflammatory cytokines and can serve as antigen-presenting cells (APCs) to prime naive T cells to recognize antigens. Thus, TLRs play an important role in linking the innate to the adaptive immune response. To date, large numbers of studies have been done to investigate the role of adaptive immunity in both EAE and MS but delineating the role of innate immunity in EAE received very little focus and appreciation taking into account that it might contribute to both the initiation and progression of the disease. Moreover, EAE is not only a model to study inflammatory demyelination in the CNS; it is in general a model to study cell-mediated organ-specific autoimmune conditions. Roles of different TLRs were studied in relation to EAE and MS. More recently, some studies demonstrated the immune adjuvant properties of certain TLR ligands including TLR2, TLR4, and TLR9 in EAE. This chapter outlines different methods employed in our labs to investigate the role of TLRs in EAE model. PMID- 26803642 TI - The Use of MiRNA Antagonists in the Alleviation of Inflammatory Disorders. AB - Toll-like receptors (TLR), a family of pattern-recognition receptors (PRRs) stimulated by pathogen-associated molecular patterns (PAMPs), generate antigen triggered innate and adaptive immune responses. Recent studies have indicated that several small, regulatory RNAs, called microRNAs (miRNas), are induced by TLR activation in immune cells and that many microRNAs can control the inflammatory process and response to infection by positively or negatively regulating TLR signaling. Among these miRNAs, aberrant microRNA-155 (miR-155) has been implicated in diverse immune processes including the pathogenesis of several autoimmune diseases and cancer. Here, we discuss the role of miR-155 in TLR mediated and TLR-related immune system regulation. Furthermore, we present our current knowledge of the design, in vivo delivery strategies, and therapeutic efficacy of miR-155 inhibitors in various inflammatory disorders and cancer, including a protocol on the use of miRNA-155 inhibitors in experimental autoimmune encephalomyelitis (EAE). PMID- 26803643 TI - Investigating the Role of Toll-Like Receptors in Mouse Models of Gastric Cancer. AB - Gastric cancer (GC) is the second most lethal cancer world-wide, and the poor overall 5-year survival rate of <25 % for GC is largely due to both the late detection of this aggressive disease and limited effectiveness of current treatment options. Collectively, these observations underscore the need to identify new molecular targets (i.e., genes) to serve as biomarkers for early detection and/or treatment strategies to improve patient outcomes. While GC represents a growing number of cancers whereby deregulation of the immune system is linked to tumor initiation and progression, the identity of innate immune regulators with oncogenic potential in the host gastric mucosal epithelium remains obscure. Over the last couple of decades experimental mouse models for many cancer types have been widely used with great success to identify genes whose expression and/or mutation status influences tumorigenesis. Considering the recent mounting evidence for the role of innate immunity in the pathogenesis of inflammation-associated cancers such as GC, much attention has focused on members of the Toll-like receptor (TLR) family, which are key components of the innate immune system primarily known to trigger inflammatory responses upon pathogen detection. Here, we describe techniques used on genetic mouse models for GC to examine the role of specific TLR family members in the pathogenesis of GC. PMID- 26803644 TI - Cognitive and emotional considerations for pharmacists as they deliver care in new models of pharmacy practice: New directions in social pharmacy research. PMID- 26803645 TI - The Trans-Pacific Partnership and pharmaceutical innovation. AB - Trade agreements are an overlooked area of research and policy analysis that affect market access, pricing and reimbursement decisions by pharmaceutical manufacturers, and research and development decisions in the long term. The Trans Pacific Partnership (TPP) is the most recent multi-national agreement under considerations that may have profound implications in developed and developing countries in the Pacific Rim. As in the case of other trade arrangements, the TPP negotiations are not transparent, but a major leak of the most recent draft has been published in WikiLeaks. The leaked document has raised a number of concerns about intellectual property rights (IPR) and regulatory data protection (RDP) that have implications for public health and economic policy throughout the region. In particular, IPR and RDP go beyond the minimum standards set under the World Trade Organization (WTO) and may affect drug access negatively by delaying generic drug and biosimilar product availability and by raising prices by removing national regulations dealing with drug pricing and reimbursement. Of particular concern is the establishment of a litigation process where multi national companies can sue individual countries before a panel of private attorneys who are appointed by the World Bank or United Nations. This paper addresses these concerns along with a commentary on the likelihood of occurring and the need for future research. PMID- 26803646 TI - Resting heart rate is an independent predictor of all-cause mortality in the middle aged general population. AB - BACKGROUND: High resting heart rate (RHR) predicts cardiovascular outcomes in patients with vascular disease and heart failure. We evaluated the prognostic value of RHR in a large contemporary population-based, prospective cohort of individuals without known coronary artery disease. METHODS AND RESULTS: Resting heart rate (RHR) was determined in 4091 individuals (mean age 59.2 +/- 7.7; 53 % women) from the Heinz Nixdorf RECALL study, of whom, 3348 were free of heart rate lowering medication. During 10.5 years of follow-up (median), 159 (3.9 %) individuals developed a coronary event and 398 (9.7 %) died of any cause. Persons without any event (n = 3603) had similar heart rates as persons with coronary events (69.5 +/- 11 versus 69.9 +/- 11 bpm, p = 0.51) but lower heart rates than persons who died (72.3 +/- 13 bpm, p < 0.0001). In individuals without heart rate lowering medication, an increase in heart rate by 5 bpm was associated with an increased hazard ratio (HR) for all-cause mortality of 13 % in unadjusted analysis and also upon adjustment for traditional cardiovascular risk factors, including coronary artery calcification [full model: HR (95 % CI) 1.13 (1.07 1.20), p < 0.0001], but not for coronary events [HR 1.02 (0.94-1.11), p = 0.60]. In individuals without heart rate lowering medication, the HR (full model) for heart rate >=70 versus <70 bpm with regard to all-cause mortality and coronary events was 1.68 (1.30-2.18), p < 0.0001, and 1.20 (0.82-1.77), p = 0.35. Analysis of the entire cohort revealed a continuous relationship of heart rate with all cause mortality [HR for lowest to highest heart rate quartile 1.64 (1.22-2.22), p = 0.001, full model] but not with coronary events [HR 1.04 (0.65-1.66), p = 0.86]. CONCLUSIONS: In the general population without known coronary artery disease and heart rate lowering medication, elevated RHR is an independent risk marker for all-cause mortality but not for coronary events. PMID- 26803648 TI - Diabetic Nephropathy in Women With Preexisting Diabetes: From Pregnancy Planning to Breastfeeding. AB - In women with preexisting diabetes and nephropathy or microalbuminuria, it is important to deliver careful preconception counselling to assess the risk for the mother and the foetus, for optimizing glycaemic status and to adjust medical treatment. If serum creatinine is normal in early pregnancy, kidney function is often preserved during pregnancy, but complications such as severe preeclampsia and preterm delivery are still common. Perinatal mortality is now comparable with that in women with diabetes and normal kidney function. Besides strict glycaemic control before and during pregnancy, early and intensive antihypertensive treatment is important to optimize pregnancy outcomes. Methyldopa, labetalol, nifedipine and diltiazem are considered safe, whereas angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers should be stopped before or at confirmation of pregnancy. Supplementation with folic acid in early pregnancy and low-dose aspirin from 10 to 12 weeks reduces the risk of adverse pregnancy outcomes. During breastfeeding, several ACE inhibitors are considered safe. PMID- 26803649 TI - The 2013 ACC/AHA Cholesterol Treatment Guidelines: Applicability to Patients with Diabetes. AB - Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide and the management of blood cholesterol is a cornerstone of medical therapy for the primary and secondary prevention of cardiovascular disease. Patients with diabetes represent an important high-risk group in whom clinicians should advocate the use of statins and lifestyle modification for the reduction of ASCVD. The recent 2013 ACC/AHA guidelines on managing blood cholesterol provide an important framework for the effective implementation of this important risk reduction strategy. The guidelines identify four groups of individuals who have been shown to benefit from statin therapy and update the dosing and monitoring recommendations based on evidence from published, large-scale randomized controlled trials (RCTs) with clinical hard endpoints. Primary care physicians and specialists play key roles in identifying populations at elevated ASCVD risk and providing effective care for patients, especially those with diabetes. This article will summarize the 2013 ACC/AHA guidelines on managing blood cholesterol and provide a practical management overview in order to facilitate implementation of these guidelines for patients with diabetes. PMID- 26803647 TI - Diabetic Kidney Disease in Adolescents With Type 2 Diabetes: New Insights and Potential Therapies. AB - Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) and dialysis in the Western world. Early DKD, including microalbuminuria and renal hyperfiltration, is common in adolescents with type 2 diabetes (T2D). Furthermore, youth-onset T2D carries a higher risk of progressive DKD than adult onset T2D of similar diabetes duration. DKD is characterized by a long clinically silent period without signs of disease. Therefore, a major challenge in preventing DKD is the difficulty in identifying high-risk T2D patients at an early stage. The Type 2 Diabetes in Adolescents and Youth (TODAY) study demonstrated a high initial prevalence that increased over time, irrespective of treatment arm. This key observation underscores the importance of discovering new therapeutic targets to supplement conventional management, in order to reduce DKD risk. In this review, we focus on early DKD in T2D and summarize potential novel biomarkers and therapeutic targets. PMID- 26803650 TI - Hyperglycemia and Diabetes Mellitus Following Organ Transplantation. AB - Hyperglycemia is common following organ transplantation, regardless of the pre transplant diabetes status. Transient post-transplant hyperglycemia and/or new onset diabetes after transplantation (NODAT) are common and are associated with increased morbidity and mortality. NODAT and type 2 diabetes share similar characteristics, but the pathophysiology may differ. Immunosuppressive agents and steroids play a key role in the development of NODAT. Glycemic control is challenging in this population due to fluctuating renal/end-organ function, immunosuppressive dosing, nutritional status, and drug-drug interactions. A proactive and multidisciplinary approach is essential, along with flexible protocols to adjust to patient status, type of organ transplanted, and corticosteroid regimens. Insulin is the preferred agent for hospitalized patients and during the early post-transplant period; optimal glycemic control (BG < 180 mg/dl with minimal hypoglycemia [<70 mg/dl]) is desired. PMID- 26803651 TI - Genetics of Gestational Diabetes Mellitus and Maternal Metabolism. AB - Gestational diabetes mellitus (GDM) is defined as abnormal glucose tolerance with onset or first recognition during pregnancy. Women with a history of GDM are at long-term risk for developing type 2 diabetes (T2DM), raising the question to what extent GDM and T2DM share a common genetic architecture. Meta-analysis of candidate gene studies and genome-wide association analysis (GWAS) have identified a number of genes which are reproducibly associated with GDM, including TCF7L2, GCK, KCNJ11, KCNQ1, CDKAL1, IGF2BP2, MTNR1B, and IRS1. These genes are also associated with T2DM. Candidate gene and GWAS have also identified genes associated with maternal metabolic traits, most of which are also associated with metabolic traits in the general population. Two genes, BACE2 and HKDC1, are uniquely associated with maternal metabolic traits. These studies suggest that there are similarities and differences between the genetic architecture of GDM and T2DM and metabolic quantitative traits in pregnant and non-pregnant populations. PMID- 26803652 TI - Diabetes and Schizophrenia. AB - People with schizophrenia have 2- to 5-fold higher risk of type 2 diabetes than the general population. The traditional risk factors for type 2 diabetes, especially obesity, poor diet, and sedentary lifestyle, are common in people with schizophrenia already early in the course of illness. People with schizophrenia also often have low socioeconomic status and income, which affects their possibilities to make healthy lifestyle choices. Antipsychotic medications increase the risk of type 2 diabetes both directly by affecting insulin sensitivity and indirectly by causing weight gain. Lifestyle modification interventions for prevention of diabetes should be an integral part of treatment of patients with schizophrenia. In the treatment of type 2 diabetes in patients with schizophrenia, communication and collaboration between medical care and psychiatric treatment providers are essential. PMID- 26803653 TI - Evaluation of different nitrous oxide production models with four continuous long term wastewater treatment process data series. AB - Five activated sludge models describing N2O production by ammonium oxidising bacteria (AOB) were compared to four different long-term process data sets. Each model considers one of the two known N2O production pathways by AOB, namely the AOB denitrification pathway and the hydroxylamine oxidation pathway, with specific kinetic expressions. Satisfactory calibration could be obtained in most cases, but none of the models was able to describe all the N2O data obtained in the different systems with a similar parameter set. Variability of the parameters can be related to difficulties related to undescribed local concentration heterogeneities, physiological adaptation of micro-organisms, a microbial population switch, or regulation between multiple AOB pathways. This variability could be due to a dependence of the N2O production pathways on the nitrite (or free nitrous acid-FNA) concentrations and other operational conditions in different systems. This work gives an overview of the potentialities and limits of single AOB pathway models. Indicating in which condition each single pathway model is likely to explain the experimental observations, this work will also facilitate future work on models in which the two main N2O pathways active in AOB are represented together. PMID- 26803654 TI - The use of runs of homozygosity for estimation of recent inbreeding in Holstein cattle. AB - Controlling inbreeding in livestock populations is of great importance because excess relatedness among animals leads to a rapid loss of genetic variation and to adverse phenotypical effects associated with an inbreeding depression. Recent advances in genotyping technology have made it possible to study inbreeding at a molecular level by the analysis of genome-wide single nucleotide polymorphism panels. In this study, we used BovineSNP50 assay (Illumina) to estimate genomic inbreeding coefficient in 298 Holstein cattle by the analysis of the genome portion in runs of homozygosity (FROH) or using genomic relationship matrix (FGRM), and compared this data with conventional pedigree-based inbreeding coefficients (FPED). Weak or moderate Spearman's rank correlations were observed between FROH and FPED which depended on the ROH length categories used for calculations and inclusion of animals with different number of complete generations registered in pedigrees. The highest correlations were observed when using ROH with lengths over 8 Mb (0.334). The correlations tended to increase as pedigree depth increased, and were the highest for animals with seven complete generations of pedigree data. FGRM correlated poorly with pedigree-based estimates, which suggests that ROH-based inbreeding coefficients better reflect recent relatedness among animals. PMID- 26803656 TI - Endorsement of universal health coverage financial principles in Burkina Faso. AB - In West Africa, health system funding rarely involves cross-subsidization among population segments. In some countries, a few community-based or professional health insurance programs are present, but coverage is very low. The financial principles underlying universal health coverage (UHC) sustainability and solidarity are threefold: 1) anticipation of potential health risks; 2) risk sharing and; 3) socio-economic status solidarity. In Burkina Faso, where decision makers are favorable to national health insurance, we measured endorsement of these principles and discerned which management configurations would achieve the greatest adherence. We used a sequential exploratory design. In a qualitative step (9 interviews, 12 focus groups), we adapted an instrument proposed by Goudge et al. (2012) to the local context and addressed desirability bias. Then, in a quantitative step (1255 respondents from the general population), we measured endorsement. Thematic analysis (qualitative) and logistic regressions (quantitative) were used. High levels of endorsement were found for each principle. Actual practices showed that anticipation and risk sharing were not only intentions. Preferences were given to solidarity between socio-economic status (SES) levels and progressivity. Although respondents seemed to prefer the national level for implementation, their current solidarity practices were mainly focused on close family. Thus, contribution levels should be set so that the entire family benefits from healthcare. Some critical conditions must be met to make UHC financial principles a reality through health insurance in Burkina Faso: trust, fair and mandatory contributions, and education. PMID- 26803655 TI - Does integration of HIV and sexual and reproductive health services improve technical efficiency in Kenya and Swaziland? An application of a two-stage semi parametric approach incorporating quality measures. AB - Theoretically, integration of vertically organized services is seen as an important approach to improving the efficiency of health service delivery. However, there is a dearth of evidence on the effect of integration on the technical efficiency of health service delivery. Furthermore, where technical efficiency has been assessed, there have been few attempts to incorporate quality measures within efficiency measurement models particularly in sub-Saharan African settings. This paper investigates the technical efficiency and the determinants of technical efficiency of integrated HIV and sexual and reproductive health (SRH) services using data collected from 40 health facilities in Kenya and Swaziland for 2008/2009 and 2010/2011. Incorporating a measure of quality, we estimate the technical efficiency of health facilities and explore the effect of integration and other environmental factors on technical efficiency using a two stage semi-parametric double bootstrap approach. The empirical results reveal a high degree of inefficiency in the health facilities studied. The mean bias corrected technical efficiency scores taking quality into consideration varied between 22% and 65% depending on the data envelopment analysis (DEA) model specification. The number of additional HIV services in the maternal and child health unit, public ownership and facility type, have a positive and significant effect on technical efficiency. However, number of additional HIV and STI services provided in the same clinical room, proportion of clinical staff to overall staff, proportion of HIV services provided, and rural location had a negative and significant effect on technical efficiency. The low estimates of technical efficiency and mixed effects of the measures of integration on efficiency challenge the notion that integration of HIV and SRH services may substantially improve the technical efficiency of health facilities. The analysis of quality and efficiency as separate dimensions of performance suggest that efficiency may be achieved without sacrificing quality. PMID- 26803657 TI - Taurine content in different brain structures during ageing: effect on hippocampal synaptic plasticity. AB - A reduction in taurine content accompanies the ageing process in many tissues. In fact, the decline of brain taurine levels has been associated with cognitive deficits whereas chronic administration of taurine seems to ameliorate age related deficits such as memory acquisition and retention. In the present study, using rats of three age groups (young, adult and aged) we determined whether the content of taurine and other amino acids (glutamate, serine, glutamine, glycine, alanine and GABA) was altered during ageing in different brain areas (cerebellum, cortex and hippocampus) as well non-brain tissues (heart, kidney, liver and plasma). Moreover, using hippocampal slices we tested whether ageing affects synaptic function and plasticity. These parameters were also determined in aged rats fed with either taurine-devoid or taurine-supplemented diets. With age, we found heterogeneous changes in amino acid content depending on the amino acid type and the tissue. In the case of taurine, its content was reduced in the cerebellum of adult and aged rats, but it remained unchanged in the hippocampus, cortex, heart and liver. The synaptic response amplitude decreased in aged rats, although the late phase of long-term synaptic potentiation (late-LTP), a taurine dependent process, was not altered. Our study highlights the stability of taurine content in the hippocampus during ageing regardless of whether taurine was present in the diet, which is consistent with the lack of changes detected in late-LTP. These results indicate that the beneficial effects of taurine supplementation might be independent of the replenishment of taurine stores. PMID- 26803658 TI - CK1delta kinase activity is modulated by protein kinase C alpha (PKCalpha) mediated site-specific phosphorylation. AB - Cellular signal transduction components are usually regulated not only on transcriptional or translational level, but also by posttranslational modifications. Among these, reversible phosphorylation represents the most abundant modification. In general, phosphorylation events are essential for regulating the activity of central signal transduction proteins, also including kinases itself. Members of the CK1 family can be found as central signal transduction proteins in numerous cellular pathways. Due to its wide variety of cellular functions the activity of CK1 family members has to be tightly regulated. We previously reported that PKA and Chk1 are able to phosphorylate CK1delta within its C-terminal regulatory domain, consequently resulting in altered CK1 kinase activity. In the present study, we show by several methods that protein kinase C alpha (PKCalpha) as well is able to phosphorylate CK1delta at its C-terminally located residues S328, T329, and S370. Furthermore, we analyze the functional consequences of PKCalpha-mediated phosphorylation on CK1delta kinase activity. Mutation of S328, T329, or S370 to alanine dramatically alters the kinetic parameters of CK1delta. By using the PKCalpha-specific inhibitor Go-6983 in a selected cell culture model, we finally show that the in vitro detected regulatory connection between PKCalpha and CK1delta is also relevant in the cellular context. Taken together, these data contribute to a deeper understanding of cellular signal transduction networks thereby helping to form a basis for the development of future therapeutic concepts. PMID- 26803659 TI - High-resolution proteomic profiling of spider venom: expanding the toxin diversity of Phoneutria nigriventer venom. AB - Here we present a proteomic characterization of Phoneutria nigriventer venom. A shotgun proteomic approach allowed the identification, for the first time, of O glycosyl hydrolases (chitinases) in P. nigriventer venom. The electrophoretic profiles under nonreducing and reducing conditions, and protein identification by mass spectrometry, indicated the presence of oligomeric toxin structures in the venom. Complementary proteomic approaches allowed for a qualitative and semi quantitative profiling of P. nigriventer venom complexity, expanding its known venom proteome diversity. PMID- 26803660 TI - Reaching out for scientific legacy: how to define authorship in academic publishing. PMID- 26803661 TI - Effect of long-term industrial waste effluent pollution on soil enzyme activities and bacterial community composition. AB - Although numerous studies have addressed the influence of exogenous pollutants on microorganisms, the effect of long-term industrial waste effluent (IWE) pollution on the activity and diversity of soil bacteria was still unclear. Three soil samples characterized as uncontaminated (R1), moderately contaminated (R2), and highly contaminated (R3) receiving mixed organic and heavy metal pollutants for more than 20 years through IWE were collected along the Mahi River basin, Gujarat, western India. Basal soil respiration and in situ enzyme activities indicated an apparent deleterious effect of IWE on microbial activity and soil function. Community composition profiling of soil bacteria using 16S rRNA gene amplification and denaturing gradient gel electrophoresis (DGGE) method indicated an apparent bacterial community shift in the IWE-affected soils. Cloning and sequencing of DGGE bands revealed that the dominated bacterial phyla in polluted soil were affiliated with Firmicutes, Acidobacteria, and Actinobacteria, indicating that these bacterial phyla may have a high tolerance to pollutants. We suggested that specific bacterial phyla along with soil enzyme activities could be used as relevant biological indicators for long-term pollution assessment on soil quality. Graphical Abstract Bacterial community profiling and soil enzyme activities in long-term industrial waste effluent polluted soils. PMID- 26803662 TI - Bioavailability of riverine dissolved organic carbon and nitrogen in the Heilongjiang watershed of northeastern China. AB - The bioavailabilities of dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) were examined in eight sampling stations of the Heilongjiang watershed, located in Heilongjiang Province, northeast China. Water samples were incubated for 55 days at 20 degrees C, and the decreases in the DOC and DON concentrations were measured during the laboratory incubations. The experiments showed that bioavailable DOC (BDOC) accounted for 15-30% of DOC and bioavailable DON (BDON) accounted for 29-57% of DON. DOM bioavailability was higher for DON compared to DOC, suggesting that DON was more bioavailable and had a faster turnover than DOC in the Heilongjiang watershed. Furthermore, the percent of bioavailable DOC (%BDOC) was significantly related to SUVA254, not the DOC concentration, suggesting that the chemistry composition of DOM played a more important role in affecting its bioavailability compared to the DOM concentration. In addition, significant negative correlations were observed between the initial DOC/DON ratios and the percent of bioavailable DOM fractions (%BDOC and %BDON), especially for %BDON, implying that low C/N molecules or N rich compounds may be preferentially utilized by microbes. Graphical Abstract DOC concentrations of eight sampling sites, microbial decomposition of DOC over 55 days, % bioavailable DOC of eight sampling sites, DOM chemical composition of eight sampling sites, demonstrated chemical composition influence on DOM bioavailability. PMID- 26803663 TI - Contaminants in sediment, food-chain biota, and bird eggs from the Newport Bay watershed, Orange County, California. AB - Groundwater-related discharges in the San Diego Creek/Newport Bay watershed in Orange County, California have the potential to adversely affect the surface waters within the watershed and would likely not comply with the established total maximum daily loads (TMDLs) for the watershed. In 2004 and 2005, we studied the concentrations of contaminants of TMDL concern (particularly selenium [Se]) in birds that are at risk of exposure to contaminated food items because they feed and nest in the Newport Bay watershed. Most bioaccumulation is from elevated Se in groundwater downstream of a historic terminal swamp. Se bioaccumulation was observed in all biota tested, and DDE was found in fish and bird egg samples. Effects of contaminants on fish and birds are inconclusive due to the management disturbances in the watershed (e.g., flood control) and lack of bird nesting habitat. Although a significant relationship was observed between DDE concentrations and eggshell thinning in American avocet (Recurvirostra americana) eggs, the shell thinning in avocet and other species examined was not enough to result in hatching failure. Further focused monitoring efforts will be needed to characterize the exposure and risk levels. PMID- 26803664 TI - Erratum. PMID- 26803665 TI - Association of Cognitive Function With Cause-Specific Mortality in Middle and Older Age: Follow-up of Participants in the English Longitudinal Study of Ageing. AB - We examined the little-tested associations between general cognitive function in middle and older age and later risk of death from chronic diseases. In the English Longitudinal Study of Ageing (2002-2012), 11,391 study participants who were 50-100 years of age at study induction underwent a battery of cognitive tests and provided a range of collateral data. In an analytical sample of 9,204 people (4,982 women), there were 1,488 deaths during follow-up (mean duration, 9.0 years). When we combined scores from 4 cognition tests that represented 3 acknowledged key domains of cognitive functioning (memory, executive function, and processing speed), cognition was inversely associated with deaths from cancer (per each 1-standard-deviation decrease in general cognitive function score, hazard ratio = 1.21, 95% CI: 1.10, 1.33), cardiovascular disease (hazard ratio = 1.71, 95% CI: 1.55, 1.89), other causes (hazard ratio = 2.07, 95% CI: 1.79, 2.40), and respiratory illness (hazard ratio = 2.48, 95% CI: 2.12, 2.90). Controlling for a range of covariates, such as health behaviors and socioeconomic status, and left-censoring to explore reverse causality had very little impact on the strength of these relationships. These findings indicate that cognitive test scores can provide relatively simple indicators of the risk of death from an array of chronic diseases and that these associations appear to be independent of other commonly assessed risk factors. PMID- 26803666 TI - Milk protein suspensions enriched with three essential minerals: Physicochemical characterization and aggregation induced by a novel enzymatic pool. AB - Structural changes of casein micelles and their aggregation induced by a novel enzymatic pool isolated from Bacillus spp. in the presence of calcium, magnesium or zinc were investigated. The effect of cations on milk protein structure was studied using fluorescence and dynamic light scattering. In the presence of cations, milk protein structure rearrangements and larger casein micelle size were observed. The interaction of milk proteins with zinc appears to be of a different nature than that with calcium or magnesium. Under the experimental conditions assayed, the affinity of each cation for some groups present in milk proteins seems to play an important role, besides electrostatic interaction. On the other hand, the lowest aggregation times were achieved at the highest calcium and zinc concentrations (15 mM and 0.25 mM, respectively). The study found that the faster the aggregation of casein micelles, the less compact the gel matrix obtained. Cation concentrations affected milk protein aggregation kinetics and the structure of the aggregates formed. PMID- 26803667 TI - The impact of atomization on the surface composition of spray-dried milk droplets. AB - The dominant presence of fat at the surface of spray-dried milk powders has been widely reported in the literature and described as resulting in unfavourable powder properties. The mechanism(s) causing this phenomenon are yet to be clearly identified. A systematic investigation of the component distribution in atomized droplets and spray-dried particles consisting of model milk systems with different fat contents demonstrated that atomization strongly influences the final surface composition. Cryogenic flash-freezing of uniform droplets from a microfluidic jet nozzle directly after atomization helped to distinguish the influence of the atomization stage from the drying stage. It was confirmed that the overrepresentation of fat on the surface is independent of the atomization technique, including a pressure-swirl single-fluid spray nozzle and a pilot-scale rotary disk spray dryer commonly used in industry. It is proposed that during the atomization stage a disintegration mechanism along the oil-water interface of the fat globules causes the surface predominance of fat. X-ray photoelectron spectroscopic measurements detected the outermost fat layer and some adjacent protein present on both atomized droplets and spray-dried particles. Confocal laser scanning microscopy gave a qualitative insight into the protein and fat distribution throughout the cross-sections, and confirmed the presence of a fat film along the particle surface. The film remained on the surface in the subsequent drying stage, while protein accumulated underneath, driven by diffusion. The results demonstrated that atomization induces component segregation and fat-rich surfaces in spray-dried milk powders, and thus these cannot be prevented by adjusting the spray drying conditions. PMID- 26803668 TI - Setting up of in-vacuum PIXE system for direct elemental analysis of thick solid environmental samples. AB - Experimental set-up, development, characterization, and calibration of an in vacuum PIXE system at the tandem accelerator facility of the Atomic Energy Commission of Syria (AECS) is described. The PIXE system calibration involved experimental characterization of the X-ray detector parameters and careful determination of the H-values that control dependence of the detector solid angle with the X-ray energies and correct imperfect values of the detector efficiency. Setting up of an electron flood gun to compensate charge built up and utilization of a beam profile monitor to perform indirect measurement of the beam charge, provide a direct PIXE measurement of thick insulating samples in-vacuum. The PIXE system has been subsequently examined to verify its ability to perform direct PIXE measurements on geological materials. A combination of minimum sample preparation procedures and specific experimental conditions applied enables simple and accurate elemental analysis. Elemental concentrations of several elements heavier than sodium in different reference geological samples, at about 5-10% absolute accuracy for most elements, have been determined. Comprehensive discussion of the obtained elemental concentration values, for most elements of visible X-ray peaks in the PIXE spectra, has been considered. PMID- 26803669 TI - Assessment of asthmatic inflammation using hybrid fluorescence molecular tomography-x-ray computed tomography. PMID- 26803670 TI - Color calibration of swine gastrointestinal tract images acquired by radial imaging capsule endoscope. PMID- 26803671 TI - Dynamic light scattering by flowing Brownian particles measured with optical coherence tomography: impact of the optical system. PMID- 26803672 TI - Plantar loading changes with alterations in foot strike patterns during a single session in habitual rear foot strike female runners. AB - OBJECTIVES: Characterize plantar loading parameters when habitually rear foot strike (RFS) runners change their pattern to a non-rear foot strike (NRFS). DESIGN: Experimental. SETTING: University biomechanics laboratory. PARTICIPANTS: Twenty three healthy female runners (Age: 22.17 +/- 1.64 yrs; Height: 168.91 +/- 5.46 cm; Mass: 64.29 +/- 7.11 kg). MAIN OUTCOME MEASURES: Plantar loading was measured using an in-sole pressure sensor while running down a 20-m runway restricted to a range of 3.52-3.89 m/s under two conditions, using the runner's typical RFS, and an adapted NRFS pattern. Repeated measures multivariate analysis of variance was performed to detect differences in loading between these two conditions. RESULTS: Force and pressure variables were greater in the forefoot and phalanx in NRFS and greater in the heel and mid foot in RFS pattern, but the total force imposed upon the whole foot and contact time remained similar between conditions. Total peak pressure was higher and contact area was lower during NRFS running. CONCLUSIONS: The primary finding of this investigation is that there are distinctly different plantar loads when changing from a RFS to NRFS during running. So, during a transition from RFS to a NRFS pattern; a period of acclimation should be considered to allow for adaptations to these novel loads incurred on plantar regions of the foot. PMID- 26803673 TI - Can stature be estimated from tooth crown dimensions? A study in a sample of South-East Asians. AB - OBJECTIVE: Stature estimation is an important step during medico-legal and forensic examination. Difficulty arises when highly decomposed and mutilated dead bodies with fragmentary remains are brought for forensic identification like in mass disaster or airplane crash. The body remains could be just a jaw with some teeth. The objective of this study was to explore if the stature of an individual can be determined from the tooth crown dimensions. DESIGN: A total of 201 volunteers participated in this study. The stature and clinical crown dimensions (length, mesiodistal and labiolingual diameters) of maxillary anterior teeth were measured. Correlation between crown dimensions and stature was analyzed by Pearson correlation test. Regression analysis was used to get equations for estimation of stature from crown measurements. The regression equations were applied in the same sample of volunteers that was used to obtain the equations. The reliability and accuracy of the equations were checked in another sample of volunteers. RESULTS: Length and mesiodistal diameter of the crown of central incisors and canines showed significant albeit low to moderate correlations (0.35 0.45) with the stature. The correlation co-efficient values were higher (as high as 0.537) when summation of the measurements was taken for analysis. The regression equations when applied to the same and a test sample of volunteers revealed that differences between actual and estimated stature can be as low as 0.01 to as much as 16.50cm. CONCLUSION: The findings suggest that although there are some degrees of positive correlations between stature and tooth crown dimensions, stature estimation from the tooth crown dimensions cannot provide the accuracy of estimation as required in forensic situations. The stature estimation accuracy using tooth crown dimensions is comparable to that of cephalo-facial dimensions but inferior to that of long bones. PMID- 26803674 TI - Influence of Candida krusei and Candida glabrata on Candida albicans gene expression in in vitro biofilms. AB - OBJECTIVE: The present study aimed to evaluate the interactions between the species Candida albicans, Candida krusei and Candida glabrata in monotypic and mixed biofilm models formed in vitro as well as the relative expression of the ALS1, ALS3, HWP1, BCR1, EFG1, TEC1, SAP5, PLB2 and LIP9 genes. MATERIAL AND METHODS: Mixed (C. albicans/C. krusei and C. albicans/C. glabrata) and monotypic biofilms were cultured for 0, 12 and 24h. Gene expression was analyzed in the same biofilm model in which the number of CFU/mL was counted. RESULTS: The C. albicans CFU/mL values were lower at the 12 and 24h time points in the mixed biofilms compared with the monotypic biofilms, and decreases of 56.23% and 64.4% in C. albicans were observed when this species was associated with C. glabrata and C. krusei, respectively. In the presence of C. krusei, the expression of the ALS3, HWP1, BCR1, EFG1 and TEC1 genes of C. albicans was completely inhibited, indicating both transcriptome and the phenotypic antagonism between these two species, but genes related to the secretion of enzymes were stimulated. In the presence of C. glabrata, C. albicans showed a similar gene expression profile to that obtained in association with C. krusei, though it was altered to a lesser degree. CONCLUSION: We conclude that C. krusei and C. glabrata may alter or inhibit the mechanisms involved in the in vitro adherence and formation of C. albicans biofilms, influencing the pathogenicity of this species and suggesting a competitive interaction with C. krusei and C. glabrata in biofilm formation. PMID- 26803675 TI - Kinematic parameters of hand movement during a disparate bimanual movement task in children with unilateral Cerebral Palsy. AB - Children with unilateral Cerebral Palsy (uCP) experience problems performing tasks requiring the coordinated use of both hands (bimanual coordination; BC). Additionally, some children with uCP display involuntary symmetrical activation of the opposing hand (mirrored movements). Measures, used to investigate therapy related improvements focus on the functionality of the affected hand during unimanual or bimanual tasks. None however specifically address spatiotemporal integration of both hands. We explored the kinematics of hand movements during a bimanual task to identify parameters of BC. Thirty-seven children (aged 10.9+/ 2.6years, 20 male) diagnosed with uCP participated. 3D kinematic motion analysis was performed during the task requiring opening of a box with their affected- (AH) or less-affected hand (LAH), and pressing a button inside with the opposite hand. Temporal and spatial components of data were extracted and related to measures of hand function and level of impairment. Total task duration was correlated with the Jebsen-Taylor Test of Hand Function in both conditions (either hand leading with the lid-opening). Spatial accuracy of the LAH when the box was opened with their AH was correlated with outcomes on the Children's Hand Use Experience Questionnaire. Additionally, we found a subgroup of children displaying non-symmetrical movement interference associated with greater movement overlap when their affected hand opened the box. This subgroup also demonstrated decreased use of the affected hand during bimanual tasks. Further investigation of bimanual interference, which goes beyond small scaled symmetrical mirrored movements, is needed to consider its impact on bimanual task performance following early unilateral brain injury. PMID- 26803676 TI - Coupling of postural and manual tasks in expert performers. AB - The purpose of this study was to investigate the integration of bimanual rhythmic movements and posture in expert marching percussionists. Participants (N=11) performed three rhythmic manual tasks [1:1, 2:3, and 2:3-F (2:3 rhythm played faster at a self-selected tempo)] in one of three postures: sitting, standing on one foot, and standing on two feet. Discrete relative phase, postural time-to contact, and coherence analysis were used to analyze the performance of the manual task, postural control, and the integration between postural and manual performance. Across all three rhythms, discrete relative phase mean and variability results showed no effects of posture on rhythmic performance. The complexity of the manual task (1:1 vs. 2:3) had no effect on postural time-to contact. However, increasing the tempo of the manual task (2:3 vs. 2:3-F) did result in a decreased postural time-to-contact in the two-footed posture. Coherence analysis revealed that the coupling between the postural and manual task significantly decreased as a function of postural difficulty (going from a two-footed to a one-footed posture) and rhythmic complexity (1:1 vs. 2:3). Taken together, these results demonstrate that expert marching percussionists systematically decouple postural and manual fluctuations in order to preserve the performance of the rhythmic movement task. PMID- 26803677 TI - Clinical and functional impact of inhaled antibiotics in a Portuguese Pulmonology Department. PMID- 26803678 TI - A cross-sectional study with an improved methodology to assess occupational air pollution exposure and respiratory health in motorcycle taxi driving. AB - INTRODUCTION: Motorcycle taxi driving is common in many African cities. This study tested whether this occupation is associated with more respiratory disorders in a context of widespread urban air pollution with an improved methodology. METHODS: In a cross sectional study we compared 85 male motorcycle taxi drivers in the capital city of the Republic of Benin (Cotonou) with an age and neighborhood matched control group. All participants carried a portable carbon monoxide data logger for 8 hours per day to assess exposure to air pollution. Respiratory symptoms were obtained using a standardized questionnaire and pulmonary function was assessed by spirometry. RESULTS: The two groups did not differ significantly (p>0.10) in their age, height, educational level, and exposures to smoke from biomass fuels and tobacco products. The taxi drivers were exposed to higher mean (SD) levels of carbon monoxide (7.6+/-4.9ppmvs. 5.4+/ 3.8ppm p=0.001). They reported more phlegm and tended to have slightly lower levels of lung function, although these differences were not statistically significant. CONCLUSION: In this cross sectional study of young motorcycle taxi drivers with substantial exposure to urban traffic and a matched control group, we found no evidence for respiratory impairment. A follow-up of such study population with other pollution exposure surrogate and other clinical endpoint may provide a more robust conclusion regarding the exposure response in this professional group. PMID- 26803679 TI - Extravagance in the commons: Resource exploitation and the frontiers of ecosystem service depletion in the Amazon estuary. AB - Estuaries hold major economic potential due their strategic location, close to seas and inland waterways, thereby supporting intense economic activity. The increasing pace of human development in coastal deltas over the past five decades has also strained local resources and produced extensive changes across both social and ecological systems. The Amazon estuary is located in the Amazon Basin, North Brazil, the largest river basin on Earth and also one of the least understood. A considerable segment of the population living in the estuary is directly dependent on the local extraction of natural resources for their livelihood. Areas sparsely inhabited may be exploited with few negative consequences for the environment. However, recent and increasing pressure on ecosystem services is maximised by a combination of factors such as governance, currency exchange rates, exports of beef and forest products. Here we present a cross methodological approach in identifying the political frontiers of forest cover change in the estuary with consequences for ecosystem services loss. We used a combination of data from earth observation satellites, ecosystem service literature, and official government statistics to produce spatially-explicit relationships linking the Green Vegetation Cover to the availability of ecosystems provided by forests in the estuary. Our results show that the continuous changes in land use/cover and in the economic state have contributed significantly to changes in key ecosystem services, such as carbon sequestration, climate regulation, and the availability of timber over the last thirty years. PMID- 26803680 TI - More than a century of Grain for Green Program is expected to restore soil carbon stock on alpine grassland revealed by field (13)C pulse labeling. AB - Anthropogenic changes in land use/cover have altered the vegetation, soil, and carbon (C) cycling on the Qinghai-Tibetan Plateau (QTP) over the last ~50years. As a result, the Grain for Green Program (GfGP) has been widely implemented over the last 10years to mitigate the impacts of cultivation. To quantify the effects of the GfGP on C partitioning and turnover rates at the ecosystem scale, an in situ (13)C pulse labeling experiment was conducted on natural and GfGP grasslands in an agro-pastoral ecotone in the Lake Qinghai region on the QTP. We found that there were significant differences in the C stocks of all the considered pools in both the natural and GfGP grasslands, with higher CO2 uptake rates in the GfGP grassland than that in the natural grassland. Partitioning of photoassimilate (% of recovered (13)C) in C pools of both grasslands was similar 25days after labeling, except in the roots of the 0-15 and 5-15cm soil layer. Soil organic C (SOC) sequestration rate in the GfGP grassland was 11.59+/-1.89gCm(-2)yr(-1) significantly greater than that in the natural grassland. The results confirmed that the GfGP is an efficient approach for grassland restoration and C sequestration. However, it will take more than a century (119.19+/-20.26yr) to restore the SOC stock from the current cropland baseline level to the approximate level of natural grassland. We suggest that additional measures are needed in the selection of suitable plant species for vegetation restoration, and in reasonable grazing management. PMID- 26803681 TI - Correlation of the seasonal isotopic amplitude of precipitation with annual evaporation and altitude in alpine regions. AB - The time series of stable water isotope composition relative to IAEA-GNIP meteorological stations located in alpine zones are analyzed in order to study how the amplitude of the seasonal isotopic composition of precipitation (Adelta) varies along a vertical transect. A clear relationship between Adelta and local evaporation is obtained, with slopes of -0.87 0/00/100mm/yr and -7.3 0/00/100mm/yr for Adelta(18)O and Adelta(2)H, respectively. When all sampling points of the vertical transect receive the same moisture sources, then a linear relationship between Adelta and elevation is obtained, with vertical gradients of 0.16 0/00/100mm/yr and 1.46 0/00/100mm/yr forAdelta(18)O and Adelta(2)H, respectively. PMID- 26803682 TI - Did summer weather factors affect gastrointestinal infection hospitalizations in New York State? AB - BACKGROUND: Gastrointestinal infections, a substantial public health problem worldwide, have been associated with single weather factors but the joint effect of multiple weather factors on gastrointestinal infections remains unclear. METHODS: We conducted a retrospective time-series analysis to investigate effects of weather conditions on hospitalizations for gastrointestinal infections (GIH) in New York State in July and August from 1991 to 2004. Applying generalized additive model (GAM), we evaluated the associations between daily GIH count and multiple weather factors including temperature, humidity, and precipitation (0-10 lag days), adjusting for long term trend, seasonality, and calendar effects. RESULTS: Maximum temperature, minimum temperature, and maximum universal apparent temperature (UAT) showed that each degrees C increase in temperature was significantly associated with an increase (0.70-0.96%) in daily GIH count, with the greatest impacts observed at lag 1. Extreme heat (EH: >90th percentile) (3.68% at lag 1) and precipitation (0.31% at lag 4) showed larger impacts on increases of GIH and a clear dose-response relationship for EH. Stratified analyses showed that the impacts of extreme heat on GIH tend to be greater among Hispanics, blacks, females, and those with bacterial infections. CONCLUSION: We found that high maximum and minimum temperature, UAT, precipitation, and extreme heat in summer significantly increased the risks of GIH in NYS. Our findings also suggest that bacteria might be a significant cause for GIH in the summer, and minority, female and those with bacterial infection may be more vulnerable to heat's effects on GIH. PMID- 26803683 TI - Effect of cobalt ferrite (CoFe2O4) nanoparticles on the growth and development of Lycopersicon lycopersicum (tomato plants). AB - Nanoparticles (NPs) have been synthetized and studied to be incorporated in many industrial and medical applications in recent decades. Due to their different physical and chemical properties compared with bulk materials, researchers are focused to understand their interactions with the surroundings. Living organisms such as plants are exposed to these materials and they are able to tolerate different concentrations and types of NPs. Cobalt ferrite (CoFe2O4) NPs are being studied for their application in medical sciences because of their high coercivity, anisotropy, and large magnetostriction. These properties are desirable in magnetic resonance imaging, drug delivery, and cell labeling. This study is aimed to explore the tolerance of Solanum lycopersicum L. (tomato) plants to CoFe2O4 NPs. Tomato plants were grown in hydroponic media amended with CoFe2O4 nanoparticles in a range from 0 to 1000mgL(-1). Exposure to CoFe2O4 NPs did not affect germination and growth of plants. Uptake of Fe and Co inside plant tissues increased as CoFe2O4 nanoparticle concentration was increased in the media. Mg uptake in plant leaves reached its maximum level of 4.9mgg(-1) DW (dry weight) at 125mgL(-1) of CoFe2O4 NPs exposure and decreased at high CoFe2O4 NPs concentrations. Similar pattern was observed for Ca uptake in leaves where the maximum concentration found was 10mgg(-1) DW at 125mgL(-1) of CoFe2O4 NPs exposure. Mn uptake in plant leaves was higher at 62.5mgL(-1) of CoFe2O4 NPs compared with 125 and 250mgL(-1) treatments. Catalase activity in tomato roots and leaves decreased in plants exposed to CoFe2O4 NPs. Tomato plants were able to tolerate CoFe2O4 NPs concentrations up to 1000mgL(-1) without visible toxicity symptoms. Macronutrient uptake in plants was affected when plants were exposed to 250, 500 and 1000mgL(-1) of CoFe2O4 NPs. PMID- 26803684 TI - Airborne pollen trends in the Iberian Peninsula. AB - Airborne pollen monitoring is an effective tool for studying the reproductive phenology of anemophilous plants, an important bioindicator of plant behavior. Recent decades have revealed a trend towards rising airborne pollen concentrations in Europe, attributing these trends to an increase in anthropogenic CO2 emissions and temperature. However, the lack of water availability in southern Europe may prompt a trend towards lower flowering intensity, especially in herbaceous plants. Here we show variations in flowering intensity by analyzing the Annual Pollen Index (API) of 12 anemophilous taxa across 12 locations in the Iberian Peninsula, over the last two decades, and detecting the influence of the North Atlantic Oscillation (NAO). Results revealed differences in the distribution and flowering intensity of anemophilous species. A negative correlation was observed between airborne pollen concentrations and winter averages of the NAO index. This study confirms that changes in rainfall in the Mediterranean region, attributed to climate change, have an important impact on the phenology of plants. PMID- 26803685 TI - Influence of colloids on the attenuation and transport of phosphorus in alluvial gravel aquifer and vadose zone media. AB - Phosphorous (P) leaching (e.g., from effluents, fertilizers) and transport in highly permeable subsurface media can be an important pathway that contributes to eutrophication of receiving surface waters as groundwater recharges the base-flow of surface waters. Here we investigated attenuation and transport of orthophosphate-P in gravel aquifer and vadose zone media in the presence and absence of model colloids (Escherichia coli, kaolinite, goethite). Experiments were conducted using repacked aquifer media in a large column (2m long, 0.19m in diameter) and intact cores (0.4m long, 0.24m in diameter) of vadose zone media under typical field flow rates. In the absence of the model colloids, P was readily traveled through the aquifer media with little attenuation (up to 100% recovery) and retardation, and P adsorption was highly reversible. Conversely, addition of the model colloids generally resulted in reduced P concentration and mass recovery (down to 28% recovery), and increased retardation and adsorption irreversibility in both aquifer and vadose zone media. The degree of colloid assisted P attenuation was most significant in the presence of fine material and Fe-containing colloids at low flow rate but was least significant in the presence of coarse gravels and E. coli at high flow rate. Based on the experimental results, setback distances of 49-53m were estimated to allow a reduction of P concentrations in groundwater to acceptable levels in the receiving water. These estimates were consistent with field observations in the same aquifer media. Colloid-assisted P attenuation can be utilized to develop mitigation strategies to better manage effluent applications in gravelly soils. To efficiently retain P within soil matrix and reduce P leaching to groundwater, it is recommended to select soils that are rich in iron oxides, to periodically disturb soil preferential flow paths by tillage, and to apply a low irrigation rate. PMID- 26803686 TI - Impact on the environment from steel bridge paint deterioration using lead isotopic tracing, paint compositions and soil deconstruction. AB - Deterioration and repair of lead paint on steel structures can result in contamination of the ambient environment but other sources of lead such as from past use of leaded paint and gasoline and industrial activities can also contribute to the contamination. Using a combination of high precision lead isotopic tracing, detailed paint examination, including with scanning electron microscopy, and soil deconstruction we have compared paint on a steel bridge and bulk soil and lead-rich particles separated from soil. The majority of Pb found in the paint derives from Australian sources but some also has a probable US origin. The isotopic data for the bulk soils and selected particles lie on a mixing line with end members the geologically ancient Broken Hill lead and possible European lead which is suggested to be derived from old lead paint and industrial activities. Data for gasoline-derived particulates lie on this array and probably contribute to soil Pb. Although paint from the bridge can be a source of lead in the soils, isotopic tracing, paint morphology and mineralogical identification indicate that other sources, including from paint, gasoline and industrial activities, are contributing factors to the lead burden. Even though physical characteristics and elemental composition are the same in some particles, the isotopic signatures demonstrate that the sources are different. Plots using (206)Pb/(208)Pb vs (206)Pb/(207)Pb ratios, the common representation these days, do not allow for source discrimination in this investigation. PMID- 26803687 TI - Toxic effects of trace elements on newborns and their birth outcomes. AB - Some trace elements are essential for newborns, their deficiency may cause abnormal biological functions, whereas excessive intakes due to environmental contamination may create adverse health effects. This study was conducted to measure the levels of selected trace elements in Chinese fish consumers by assessing their essentiality and toxicity via colostrum intake in newborns, and evaluated the effects of these trace elements on birth outcomes. Trace elements in umbilical cord serum and colostrum of the studied population were relatively high compared with other populations. The geometric means (GM) of estimated daily intake (EDI, mgday(-1)) of the trace elements were in the safe ranges for infant Dietary Reference Intakes (DRIs) recommended by the United States Food and Drug Administration (FDA). When using total dietary intake (TDI, mgkg(-1)bwday(-1)), zinc (Zn) (0.880mgkg(-1)bwday(-1)) and selenium (Se) (6.39*10(-3)mgkg(-1)bwday( 1)) were above the Reference Doses (RfD), set by the United States Environmental Protection Agency (EPA). Multivariable linear regression analyses showed that Se was negatively correlated with birth outcomes. Our findings suggested that overloading of trace elements due to environmental contamination may contribute to negative birth outcomes. PMID- 26803688 TI - Childhood maltreatment and violence: mediation through psychiatric morbidity. AB - Childhood maltreatment is associated with multiple adverse outcomes in adulthood including poor mental health and violence. We investigated direct and indirect pathways from childhood maltreatment to adult violence perpetration and the explanatory role of psychiatric morbidity. Analyses were based on a population survey of 2,928 young men 21-34 years in Great Britain in 2011, with boost surveys of black and minority ethnic groups and lower social grades. Respondents completed questionnaires measuring psychiatric diagnoses using standardized screening instruments, including antisocial personality disorder (ASPD), drug and alcohol dependence and psychosis. Maltreatment exposures included childhood physical abuse, neglect, witnessing domestic violence and being bullied. Adult violence outcomes included: any violence, violence toward strangers and intimate partners (IPV), victim injury and minor violence. Witnessing domestic violence showed the strongest risk for adult violence (AOR 2.70, 95% CI 2.00, 3.65) through a direct pathway, with psychotic symptoms and ASPD as partial mediators. Childhood physical abuse was associated with IPV (AOR 2.33, 95% CI 1.25, 4.35), mediated by ASPD and alcohol dependence. Neglect was associated with violence toward strangers (AOR 1.73, 95% CI 1.03, 2.91), mediated by ASPD. Prevention of violence in adulthood following childhood physical abuse and neglect requires treatment interventions for associated alcohol dependence, psychosis, and ASPD. However, witnessing family violence in childhood had strongest and direct effects on the pathway to adult violence, with important implications for primary prevention. In this context, prevention strategies should prioritize and focus on early childhood exposure to violence in the family home. PMID- 26803689 TI - Comparison of medication policies to guide nursing practice across seven Victorian health services. AB - Objectives The objective of this paper is to review and compare the content of medication management policies across seven Australian health services located in the state of Victoria. Methods The medication management policies for health professionals involved in administering medications were obtained from seven health services under one jurisdiction. Analysis focused on policy content, including the health service requirements and regulations governing practice. Results and Conclusions The policies of the seven health services contained standard information about staff authorisation, controlled medications and poisons, labelling injections and infusions, patient self-administration, documentation and managing medication errors. However, policy related to individual health professional responsibilities, single- and double-checking medications, telephone orders and expected staff competencies varied across the seven health services. Some inconsistencies in health professionals' responsibilities among medication management policies were identified. What is known about the topic? Medication errors are recognised as the single most preventable cause of patient harm in hospitals and occur most frequently during administration. Medication management is a complex process involving several management and treatment decisions. Policies are developed to assist health professionals to safely manage medications and standardise practice; however, co occurring activities and interruptions increase the risk of medication errors. What does this paper add? In the present policy analysis, we identified some variation in the content of medication management policies across seven Victorian health services. Policies varied in relation to medications that require single- and double-checking, as well as by whom, nurse-initiated medications, administration rights, telephone orders and competencies required to check medications. What are the implications for practitioners? Variation in medication management policies across organisations is highlighted and raises concerns regarding consistency in governance and practice related to medication management. Lack of practice standardisation has previously been implicated in medication errors. Lack of intrajurisdictional concordance should be addressed to increase consistency. Inconsistency in expectations between healthcare services may lead to confusion about expectations among health professionals moving from one healthcare service to another, and possibly lead to increased risk of medication errors. PMID- 26803690 TI - Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade: A Randomized Clinical Trial. AB - BACKGROUND: In patients with chronic kidney disease receiving renin-angiotensin aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown. We therefore studied the effects of dietary sodium restriction on BP and urinary albumin excretion (UAE) in kidney transplant recipients receiving RAAS blockade. STUDY DESIGN: Two center randomized crossover trial. SETTING & PARTICIPANTS: Stable outpatient kidney transplant recipients with creatinine clearance > 30mL/min, BP >=120/80mmHg, receiving stable RAAS blockade therapy. INTERVENTION: 6-week regular-sodium diet (target, 150mmol/24 h) and a 6-week low-sodium diet (target, 50mmol/24 h). OUTCOMES & MEASUREMENTS: Main outcome parameters were systolic and diastolic BP, UAE, and estimated glomerular filtration rate (eGFR) at the end of each diet period. Dietary adherence was assessed by 24-hour urinary sodium excretion. RESULTS: We randomly assigned 23 kidney transplant recipients, of whom 22 (mean age, 58+/-8 [SD] years; 50% men; mean eGFR, 51+/-21mL/min/1.73m(2)) completed the study. One patient withdrew from the study because of concerns regarding orthostatic hypotension on the low-sodium diet. Sodium excretion decreased from 164+/-50mmol/24 h during the regular-sodium diet to 87+/-55mmol/24 h during the low-sodium diet (mean difference, -77 [95% CI, -110 to -44] mmol/24 h; P<0.001). Sodium restriction significantly reduced systolic BP from 140+/-14 to 129+/-12mmHg (mean difference, -11 [95% CI, -14 to -7] mmHg; P<0.001), diastolic BP from 86+/-8 to 79+/-8mmHg (mean difference, -7 [95% CI, -10 to -5] mmHg; P<0.001). We found no significant effect on natural log (ln)-transformed UAE (mean difference, -0.03 [95% CI, -0.6 to 0.6] ln(mg/24 h); P=0.9) or eGFR. LIMITATIONS: No hard end points; small study; small proportion of patients willing to test the intervention; adherence to sodium diet was achieved in 86% of patients. CONCLUSIONS: In stable kidney transplant recipients receiving RAAS blockade, dietary sodium restriction effectively reduces BP without affecting eGFR. Dietary sodium restriction is relevant to BP management in kidney transplant recipients receiving RAAS blockade. PMID- 26803691 TI - Are there glutamate abnormalities in subjects at high risk mental state for psychosis? A review of the evidence. AB - New approaches to underlying alterations in psychosis suggest increasing evidence of glutamatergic abnormalities in schizophrenia and an association between these abnormalities and certain core psychopathological alterations such as cognitive impairment and negative symptoms. Proton magnetic resonance spectroscopy ((1)H MRS) is an MR-based technique that enables investigators to study glutamate function by measuring in vivo glutamatergic indices in the brain. In this article we review the published studies of (1)H MRS in subjects with an at-risk mental state (ARMS) for psychosis. The primary aim was to investigate whether alterations in glutamate function are present before the illness develops in order to expand our understanding of glutamatergic abnormalities in prodromal phases. Three databases were consulted for this review. Titles and abstracts were examined to determine if they fulfilled the inclusion criteria. The reference lists of the included studies were also examined to identify additional trials. Eleven final studies were included in this review. Significant alterations in glutamate metabolites across different cerebral areas (frontal lobe, thalamus, and the associative striatum) in subjects with an ARMS for psychosis are reported in six of the trials. A longitudinal analysis in two of these trials confirmed an association between these abnormalities and worsening of symptoms and final transition to psychosis. Considering that five other studies found no significant differences across these same areas, we can conclude that more research is needed to confirm glutamatergic abnormalities in subjects with an ARMS for psychosis. However, future research must overcome the methodological limitations of existing studies to obtain reliable results. PMID- 26803693 TI - Obsessive-compulsive symptoms interact with disorganization in influencing social functioning in schizophrenia. AB - OBJECTIVE: Recent research has suggested a dual impact of obsessive-compulsive dimension on functioning in schizophrenia with a gradual transition from an improving to a worsening effect depending on obsessive-compulsive symptoms (OCS) severity (from mild to moderate-severe). Aim of the present study was to investigate whether this varying effect of OCS on functioning might be mediated or moderated by schizophrenia symptom dimensions or occur independently. METHOD: Seventy-five patients affected by schizophrenia were administered the Structured Clinical Interview for DSM-IV Disorders, the Positive and Negative Syndrome Scale, the Yale-Brown Obsessive-Compulsive Scale and the Social and Occupational Functioning Assessment. The sample was divided into two groups according to the severity of OCS (absent/mild and moderate/high OCS group). RESULTS: In both groups, the effect of OCS on functioning was not mediated by their effect on positive, negative or disorganization symptoms. Conversely, a significant interaction between OCS and disorganization dimension was found: the dual effect of OCS on functioning occurred only among patients with low disorganization symptoms while it was no more apparent at high levels of disorganization. CONCLUSION: Data suggest that in patients with schizophrenia, functioning at least in part depends on the interaction between disorganization and OCS. PMID- 26803695 TI - Anteromedialisation tibial tubercle osteotomy for recurrent patellar instability in young active patients: A retrospective case series. AB - INTRODUCTION: Recurrent patellar instability can be a source of continued pain and functional limitation in the young, active patient population. Instability in the setting of an elevated tibial tubercle-trochlear groove (TT-TG) distance can be effectively managed with a tibial tubercle osteotomy. At the present time, clinical outcome data are limited with respect to this surgical approach to patellar instability. METHODS: A retrospective chart review was performed to identify all cases of tibial tubercle osteotomy for the management of patellar instability performed at our institution with at least 1 year of post-operative follow-up. Patient demographic information was collected along with relevant operative data. Each patient was evaluated post-operatively with their outcomes assessed utilising a visual analogue score of pain, patient satisfaction, Tegner Activity Scale and Kujala score. RESULTS: 31 patients (23 females and 8 males) with mean age of 27 years (17-43 years) and a mean BMI of 26.3kg/m(2) (19.6-35.8) at time of surgery who underwent a tibial tubercle osteotomy as treatment for recurrent patellar instability were identified. The cohort had a mean follow up of 4.4 years (1.5-11.8 years). The mean pre-operative TT-TG distance was 18mm (10 22mm). The mean VAS pain score demonstrated a significant improvement from 6.8 (95% CI 6.1-7.5) at baseline to 2.8 (95% CI 1.9-3.7) post-operatively (p<0.001). The Tegner score improved from 4.1 (95% CI 3.4-4.8) pre-operatively to 5.2 (95% CI 4.5-5.9) at the time of final follow up (p<0.04). The Kujala score for anterior knee pain improved postoperatively from 62 (95% CI 55.4-68.7) to 76.5 (95% CI 69.5-83.5) at final follow up (p<0.001). 26 of the 31 patients (83.8%) had good to excellent Kujala scores. 27 of 31 patients (87.1%) reported that they would undergo the procedure again if necessary. CONCLUSION: For the management of recurrent patellar instability in the setting of an increased tibial tubercle trochlear groove distance, a corrective tibial tubercle osteotomy is an effective treatment modality to reliably prevent patellar instability while reducing pain and improving function in this cohort of young, active patients. PMID- 26803696 TI - Lacking evidence for performance of implants used for proximal femoral fractures A systematic review. AB - INTRODUCTION: Evaluation of the long-term performance of implants used in trauma surgery relies on post-marked clinical studies since no registry based implant assessment exists. The purpose of this study was to evaluate the evidence of performance of implants currently used for treating proximal femoral fractures (PFF) in Denmark. METHOD: PubMed was searched for clinical studies on primary PFF with follow-up >=12 months, reporting implant-related failure and evaluating one of following: DHS, CHS, HipLoc, Gamma3, IMHS, InterTan, PFN, PFNA or PTN. LIMITS: English language and publication date after 1st of January 1990. RESULTS: All studies were evidence level II or III. 30 publications for SHS were found: 13 of CHS, 15 of DHS and 2 of HipLoc. In total CHS was evaluated in 1110 patients (900 prospectively), DHS in 2486 (567 prospectively) and HipLoc in 251 (all prospectively). Fifty-four publications for nails were found: 13 of Gamma3, 7 of IMHS, 5 of InterTan, 10 of PFN, 24 of PFNA and 0 of PTN. In total Gamma3 was evaluated in 1088 patients (829 prospectively), IMHS in 1543 (210 prospectively), InterTan in 595 (585 prospectively), PFN in 716 (557 prospectively), PFNA in 1762 (1018 prospectively) and PTN in 0. CONCLUSIONS: The clinical evidence behind the current implants used for proximal femoral fractures is weak considering the number of implants used worldwide. Sporadic evaluation is not sufficient to identify long term problems. A systematic post market surveillance of implants used for fracture treatment, preferable by a national register, is necessary in the future. PMID- 26803694 TI - Long-term follow-up of ninety eight Iranian patients with primary immune deficiency in a single tertiary centre. AB - PURPOSE: The aim was to describe the clinical manifestations, complications and long-term outcome of a cohort of Iranian patients with primary immune deficiency (PID). METHOD: We retrospectively studied the demographic, clinical and immunological characteristics of the PID patients in a single tertiary centre, from January 1989 to July 2014. The patients were classified according to the International Union of Immunological Societies Expert Committee on PID. RESULTS: 98 patients were diagnosed with and followed-up for 15 disorders. The mean age at onset and diagnosis and the diagnostic delay were 8+/-10, 14.2+/-13.1 and 6.1+/-7 years, respectively. Parental consanguinity rate was 57%. Predominantly Antibody Deficiency was the most common diagnosis (n=63), followed by congenital defects of phagocytes (n=16), combined immunodeficiencies (n=12), well defined syndromes (n=4) and defects in innate immunity (n=3). Recurrent sinopulmonary infection was the most common presentation. Active infections were treated appropriately, in addition to prophylactic therapy with IVIG and antimicrobials. Not all the patients were compliant with prophylactic regimens due to cost and unavailability. One SCID patient underwent successful bone marrow transplantation. The total mortality rate was 19% during the follow-up period (7.8+/-7.6 years). The mean age of living patients at the time of study was 23+/ 11.7 years. CONCLUSIONS: Physicians awareness of PID has been rising dramatically in Iran, ensuring an increasing number of patients being diagnosed and treated. More effective treatment services, including health insurance coverage and drug availability are needed to improve the outcome of PID patients. PMID- 26803697 TI - Intramuscular diaphragmatic stimulation for patients with traumatic high cervical injuries and ventilator dependent respiratory failure: A systematic review of safety and effectiveness. AB - BACKGROUND: Intramuscular diaphragmatic stimulation using an abdominal laparoscopic approach has been proposed as a safer alternative to traditional phrenic nerve stimulation. It has also been suggested that early implementation of diaphragmatic pacing may prevent diaphragm atrophy and lead to earlier ventilator independence. The aim of this study was therefore to systematically review the safety and effectiveness of intramuscular diaphragmatic stimulators in the treatment of patients with traumatic high cervical injuries resulting in long term ventilator dependence, with particular emphasis on the affect of timing of insertion of such stimulators. METHODS: The Cochrane database and PubMed were searched between January 2000 and June 2015. Reference lists of selected papers were also reviewed. The inclusion criteria used to select from the pool of eligible studies were: (1) reported on adult patients with traumatic high cervical injury, who were ventilator-dependant, (2) patients underwent intramuscular diaphragmatic stimulation, and (3) commented on safety and/or effectiveness. RESULTS: 12 articles were included in the review. Reported safety issues post insertion of intramuscular electrodes included pneumothorax, infection, and interaction with pre-existing cardiac pacemaker. Only one procedural failure was reported. The percentage of patients reported as independent of ventilatory support post procedure ranged between 40% and 72.2%. The mean delay of insertion ranged from 40 days to 9.7 years; of note the study with the average shortest delay in insertion reported the greatest percentage of fully weaned patients. CONCLUSIONS: Although evidence for intramuscular diaphragmatic stimulation in patients with high cervical injuries and ventilator dependent respiratory failure is currently limited, the technique appears to be safe and effective. Earlier implantation of such devices does not appear to be associated with greater surgical risk, and may be more effective. Further high quality studies are warranted to investigate the impact of delay of insertion on ventilator weaning. PMID- 26803692 TI - nAChR dysfunction as a common substrate for schizophrenia and comorbid nicotine addiction: Current trends and perspectives. AB - INTRODUCTION: The prevalence of tobacco use in the population with schizophrenia is enormously high. Moreover, nicotine dependence is found to be associated with symptom severity and poor outcome in patients with schizophrenia. The neurobiological mechanisms that explain schizophrenia-nicotine dependence comorbidity are not known. This study systematically reviews the evidence highlighting the contribution of nicotinic acetylcholine receptors (nAChRs) to nicotine abuse in schizophrenia. METHODS: Electronic data bases (Medline, Google Scholar, and Web of Science) were searched using the selected key words that match the aims set forth for this review. A total of 276 articles were used for the qualitative synthesis of this review. RESULTS: Substantial evidence from preclinical and clinical studies indicated that dysregulation of alpha7 and beta2 subunit containing nAChRs account for the cognitive and affective symptoms of schizophrenia and nicotine use may represent a strategy to remediate these symptoms. Additionally, recent meta-analyses proposed that early tobacco use may itself increase the risk of developing schizophrenia. Genetic studies demonstrating that nAChR dysfunction that may act as a shared vulnerability factor for comorbid tobacco dependence and schizophrenia were found to support this view. The development of nAChR modulators was considered an effective therapeutic strategy to ameliorate psychiatric symptoms and to promote smoking cessation in schizophrenia patients. CONCLUSIONS: The relationship between schizophrenia and smoking is complex. While the debate for the self-medication versus addiction vulnerability hypothesis continues, it is widely accepted that a dysfunction in the central nAChRs represent a common substrate for various symptoms of schizophrenia and comorbid nicotine dependence. PMID- 26803699 TI - Letter to the editor. PMID- 26803698 TI - Outcome of noncardiac surgery in children with congenital heart disease performed outside a cardiac center. AB - OBJECTIVE: The objective of this study was to review the outcome of children with congenital heart disease (CHD) undergoing noncardiac surgery requiring general anesthesia (GA) in a tertiary pediatric center between January 2010 and December 2012. STUDY DESIGN: A retrospective case note review of children <16years of age with confirmed CHD undergoing a surgical or interventional procedure requiring GA was performed. Patients were categorized into three risk groups according to White and Peyton's anesthetic risk classification of children with CHD undergoing noncardiac surgery [Critical Care and Pain 2012;12:17-22]. RESULTS: 117 children with CHD were identified with a total of 240 procedures conducted. 36 procedures were conducted in the high-risk group, 135 in the intermediate-risk group, and 69 in the low-risk group. 40% of these were major operations such as small bowel and colonic procedures. Overall mortality rate at 7days and 30days was 0% and 0.4%, respectively, with a 1% mortality rate in minor procedures and 0% mortality rate in major procedures. There were no unexpected deaths. 17% of procedures resulted in complications. A higher rate of complications was recorded in emergency procedures. 17% of these procedures required admission to the intensive care unit, with the highest admissions rate in the high-risk group. The median duration of hospital stay for the whole cohort was 1day (range of 0-71days). CONCLUSION: Our study shows that procedures requiring GA can be safely conducted on children from any of the three risk groups in a nonspecialist cardiac center provided that there is close liaison and careful planning between the different specialties. PMID- 26803700 TI - [Self-disclosure on the Net: A risk factor for problematic use of the Internet among insecure persons]. AB - INTRODUCTION: Problematic use of the Internet (PUI) is more and more commonly seen among psychiatry patients. PUI is defined as an excessive preoccupation about and use of the Internet, which can be characterized by more time spent on line than what was planned, with difficulties leading to distress or significant disorders. The new mode of interaction provided by the Internet facilitates self disclosure, especially for socially anxious persons who feel safer and more comfortable in on-line compared with face-to-face interactions. Several studies point to the fact that insecure attachment, and particularly preoccupied attachment, is associated with problematic use of the Internet. Preoccupied attachment is characterized by a negative model of self and a positive model of others. Persons with a negative model of self feel anxious in interpersonal relationships. Because self-disclosure is easier on-line, it may play a role in problematic use of the Internet. AIMS: The aim of the study is to better understand the link between insecure attachment and problematic use of the Internet, by examining the mediating role of self-disclosure. METHOD: Participants anonymously completed the following self-questionnaires on-line: the Internet Addiction Test (IAT), which assesses problematic use of the Internet, the Relationship Scale Questionnaire (RSQ), which evaluates attachment, and the "Real-me" questionnaire, which measures increased self-disclosure on the Internet compared with face-to-face interactions. SAMPLE: Participants (n=200, 73 % women) were recruited via e-mails, social networks, ads in local stores and leaflets in public places, directing them towards a link in which they could complete the on line questionnaires. DATA ANALYSIS: Descriptive analyses were conducted to examine the main characteristics of participants. A t-test was used to explore gender differences. Main analyses consisted of correlational analyses between attachment, the "Real-me", and problematic use of the Internet. A series of regression analyses were then used to test the mediating role of the "Real-me" in the link between insecure attachment and problematic use of the Internet. RESULTS: Results confirm the associations between problematic use of the Internet and, respectively, preoccupied and fearful attachment. Complete mediation of the "Real-me" in the association between negative model of self (attachment) and problematic use of the Internet was also confirmed. DISCUSSION AND CONCLUSION: Preoccupied and fearful attachments are both associated with problematic use of the Internet. These persons have a negative model of self which may hamper their ability to be at ease in face-to-face interactions. Being themselves on the Internet mediates the link between negative model of self and problematic use of the Internet. Resorting to a less threatening environment of exchange may thus explain these insecure individuals' tendency to overuse the Internet. Future research investigating the different activities on the Internet would be useful to better determine whether certain specific activities are more closely linked to problematic use of the Internet among insecure individuals. PMID- 26803701 TI - Regulatory role of Megakaryocytes on Hematopoietic Stem Cells Quiescence by CXCL4/PF4 in Bone Marrow Niche. AB - Platelet factor-4 (CXCL4/PF-4) is a member of CXC-chemokine family produced by megakaryocytic lineage and stored in platelet alpha-granules. Platelet stimulation by aggregating agents such as thrombin and ADP leads to CXCL4 secretion. CXCL4 plays several roles in coagulation, angiogenesis control, immune system modulation and spread of cancer. Megakaryocytes (Mks) are associated with the vascular niche in the bone marrow (BM) and are located in vicinity of BM sinusoids. Mk-derived CXCL4 is involved in several hematopoietic processes, including inhibition of megakaryopoiesis and maintenance of hematopoietic stem cell (HSC) quiescence. The major aim of this review article was to evaluate the role of CXCL4 in hematological malignancies, promotion of HSC quiescence as well as BM niche cells. PMID- 26803702 TI - The Price of Waiting: What Can a Province Buy for $109 Million? PMID- 26803703 TI - The Sinking STONE: What a Failed Validation Can Teach Us About Clinical Decision Rules. PMID- 26803704 TI - Formation of three-dimensional hepatic tissue by the bottom-up method using spheroids. AB - Liver regenerative medicine has attracted attention as a possible alternative to organ transplantation. To address the challenge of liver regenerative medicine, the development of a construction method has been proposed for liver tissue in vitro with a high cell density and high functionality for transplantation into patients with severe liver failure. In this study, we fabricated highly functional three-dimensional hepatic tissue by a bottom-up method using spheroids. The hepatic tissue was formed by stacking hepatocyte spheroids covered with human umbilical vein endothelial cells (HUVECs). Hepatic tissue constructs were evaluated for cell survival, liver-specific functions, and histologically. As a result, we identified improvements in liver-specific functions (ammonia removal and albumin secretion) and cell survival. In addition, HUVECs were regularly distributed at every 100 MUm within the tissue, and live cells were present within the whole tissue construct throughout the culture period. In summary, we successfully fabricated highly functional hepatic tissue by the bottom-up method using HUVEC-covered hepatocyte spheroids. PMID- 26803705 TI - Characterization and expression of the antifungal protein from Monascus pilosus and its distribution among various Monascus species. AB - Monascus species are traditionally used for food preservation. This study used the disc diffusion method to verify the antifungal activity of protein extracted from Monascus pilosus BCRC38072 against 15 fungal pathogens. An antifungal protein, designated as MAFP1, was successfully purified and confirmed through N terminal sequencing. To further explore the antifungal gene, a mafp1 gene that is similar to that of PgAFP from Penicillium chrysogenum was cloned from M. pilosus BCRC38072. According to the N-terminal sequencing and in silico analysis, the signal peptide was assumed to have 18 amino acids and the mature MAFP1 to contain 58 peptides. Moreover, the mafp1 gene was recognized in Monascus ruber, Monascus barkeri, Monascus floridanus, and Monascus lunisporas through polymerase chain reaction and DNA sequencing and showed high homology. By contrast, the mafp1 gene was absent in Monascus kaoliang, Monascus purpureus, and Monascus sanguineus. In addition, the mafp1 gene with N-terminal polyhistidine fusion was overexpressed in Escherichia coli. However, the antifungal activity of recombinant MAFP1 was significantly lower than that of native MAFP1. According to the properties of MAFP1, Monascus species may have food preservation applications. PMID- 26803706 TI - Metabolic analysis of antibody producing Chinese hamster ovary cell culture under different stresses conditions. AB - Chinese hamster ovary (CHO) cells are commonly used as the host cell lines concerning their ability to produce therapeutic proteins with complex post translational modifications. In this study, we have investigated the time course extra- and intracellular metabolome data of the CHO-K1 cell line, under a control and stress conditions. The addition of NaCl and trehalose greatly suppressed cell growth, where the maximum viable cell density of NaCl and trehalose cultures were 2.2-fold and 2.8-fold less than that of a control culture. Contrariwise, the antibody production of both the NaCl and trehalose cultures was sustained for a longer time to surpass that of the control culture. The NaCl and trehalose cultures showed relatively similar dynamics of cell growth, antibody production, and substrate/product concentrations, while they indicated different dynamics from the control culture. The principal component analysis of extra- and intracellular metabolome dynamics indicated that their dynamic behaviors were consistent with biological functions. The qualitative pattern matching classification and hierarchical clustering analyses for the intracellular metabolome identified the metabolite clusters whose dynamic behaviors depend on NaCl and trehalose. The volcano plot revealed several reporter metabolites whose dynamics greatly change between in the NaCl and trehalose cultures. The elastic net identified some critical, intracellular metabolites that are distinct between the NaCl and trehalose. While a relatively small number of intracellular metabolites related to the cell growth, glucose, glutamine, lactate and ammonium ion concentrations, the mechanism of antibody production was suggested to be very complicated or not to be explained by elastic net regression analysis. PMID- 26803707 TI - Immobilization of Lactobacillus rhamnosus in mesoporous silica-based material: An efficiency continuous cell-recycle fermentation system for lactic acid production. AB - Lactic acid bacteria immobilization methods have been widely used for lactic acid production. Until now, the most common immobilization matrix used is calcium alginate. However, Ca-alginate gel disintegrated during lactic acid fermentation. To overcome this deficiency, we developed an immobilization method in which Lactobacillus rhamnosus cells were successfully encapsulated into an ordered mesoporous silica-based material under mild conditions with a high immobilization efficiency of 78.77% by using elemental analysis. We also optimized the cultivation conditions of the immobilized L. rhamnosus and obtained a high glucose conversion yield of 92.4%. Furthermore, L. rhamnosus encapsulated in mesoporous silica-based material exhibited operational stability during repeated fermentation processes and no decrease in lactic acid production up to 8 repeated batches. PMID- 26803708 TI - Concomitant Administration of Proton Pump Inhibitors and Capecitabine is Associated With Increased Recurrence Risk in Early Stage Colorectal Cancer Patients. AB - BACKGROUND: Capecitabine is used to treat colorectal (CRC) cancer. TRIO-013, a study examining capecitabine/oxaliplatin +/- lapatinib in metastatic gastro esophageal cancer did not show increases in overall survival (OS) with lapatinib. An analysis showed concurrent proton pump inhibitor (PPI) usage negatively impacted recurrence-free survival (RFS). We retrospectively studied PPI effects on capecitabine efficacy in early stage CRC and how capecitabine adjustments impacted RFS. METHODS: Early stage CRC patients taking monotherapy capecitabine treated from 2008 to 2012 were reviewed for demographics, medications, toxicities, and patient outcomes. RESULTS: Of 298 identified patients, 25.8% (n = 77) received concurrent PPIs. Five-year RFS was 74% versus 83% (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.07-3.35; P = .03) in PPI versus non PPI patients respectively. OS was 81% versus 78%, respectively (HR, 1.13; 95% CI, 0.60-2.14; P = .7). After accounting for gender, stage, age, and performance status, PPI patients tended toward decreased RFS (HR, 1.65; 95% CI, 0.93-2.94; P = .09). Capecitabine dose modifications affected outcomes. Five-year RFS was 84% in the control group, 100% in the treatment-delay group (P = .99), 67% in the dose reduction group (HR, 2.46; 95% CI, 1.23-4.93; P = .01), and 64% in the discontinuation group (HR, 2.27; 95% CI, 0.93-5.53; P = .07). Five-year OS was significantly less in the discontinuation group than control group (59% vs. 82%; HR, 3.27; 95% CI, 1.44-7.45; P = .005). CONCLUSIONS: PPIs appear to impact RFS; this may be due to PPIs preventing capecitabine tablet dissolution and absorption. Patients with dose reductions or who stopped treatment had worse outcomes than patients who continued with treatment at starting doses. PMID- 26803709 TI - Primary Tumor Resection and Overall Survival in Patients With Metastatic Colorectal Cancer Treated With Palliative Intent. AB - BACKGROUND: The survival impact of primary tumor resection in patients with metastatic colorectal cancer (mCRC) treated with palliative intent remains uncertain. In the absence of randomized data, the objectives of the present study were to examine the effect of primary tumor resection (PTR) and major prognostic variables on overall survival (OS) of patients with de novo mCRC. PATIENTS AND METHODS: Consecutive patients from the Australian 'Treatment of Recurrent and Advanced Colorectal Cancer' registry were examined from June 2009 to March 2015. Univariate and multivariate Cox proportional hazards regression analyses were used to identify associations between multiple patient or clinical variables and OS. Patients with metachronous mCRC were excluded from the analyses. RESULTS: A total of 690 patients de novo and 373 metachronous mCRC patients treated with palliative intent were identified. The median follow-up period was 30 months. The median age of de novo patients was 66 years; 57% were male; 77% had an Eastern Cooperative Oncology Group performance status of 0 to 1; and 76% had a colon primary. A total of 216 de novo mCRC patients treated with palliative intent underwent PTR at diagnosis and were more likely to have a colon primary (odds ratio [OR], 15.4), a lower carcinoembryonic antigen level (OR, 2.08), and peritoneal involvement (OR, 2.58; P < .001). On multivariate analysis, PTR at diagnosis in de novo patients was not associated with significantly improved OS (hazard ratio [HR], 0.82; 99% confidence interval [CI], 0.62-1.09; P = .068). PTR at diagnosis did not correlate with outcome in de novo patients with a colon primary (HR, 0.74; 99% CI, 0.54-1.01; P = .014) or a rectal primary (HR, 0.81; 99% CI, 0.27-2.44; P = .621). CONCLUSION: For de novo mCRC patients treated with palliative intent, PTR at diagnosis does not significantly improve OS when adjusting for known major prognostic factors. The outcomes of randomized trials examining the survival impact of PTR are awaited. PMID- 26803710 TI - Electroconvulsive therapy clinical database: Influence of age and gender on the electrical charge. AB - INTRODUCTION: The influence of age and gender in the electrical charge delivered in a given population was analysed using an electroconvulsive therapy (ECT) clinical database. MATERIAL AND METHOD: An observational, prospective, longitudinal study with descriptive analysis was performed using data from a database that included total bilateral frontotemporal ECT carried out with a Mecta spECTrum 5000Q(r) in our hospital over 6 years. From 2006 to 2012, a total of 4,337 ECT were performed on 187 patients. Linear regression using mixed effects analysis was weighted by the inverse of the number of ECT performed on each patient per year of treatment. RESULTS: The results indicate that age is related with changes in the required charge (P=.031), as such that the older the age a higher charge is needed. Gender is also associated with changes in charge (P=.014), with women requiring less charge than men, a mean of 87.3mC less. When the effects of age and gender are included in the same model, both are significant (P=.0080 and P=.0041). Thus, for the same age, women require 99.0mC less charge than men, and in both genders the charge increases by 2.3mC per year. CONCLUSIONS: From our study, it is concluded that the effect of age on the dosage of the electrical charge is even more significant when related to gender. It would be of interest to promote the systematic collection of data for a better understanding and application of the technique. PMID- 26803711 TI - The Timing of Total Hip Arthroplasty After Intraarticular Hip Injection Affects Postoperative Infection Risk. AB - BACKGROUND: The data regarding any association between preoperative intraarticular steroid injection and risk ofperiprosthetic joint infection (PJI) after total hip arthroplasty (THA) are conflicting. The goal of the present study is to evaluate the association of preoperative intraarticular hip injection before THA on the incidence of postoperative PJI. METHODS: A national database was queried for patients who underwent THA and those patients who underwent prior ipsilateral hip injection. Three cohorts were created: THA within 3 months of ipsilateral hip injection (n = 829), THA between 3 and 6 months after ipsilateral hip injection (n= 1379), and THA between 6 and 12months after ipsilateral hip injection (n=1160). A control group of THAwithout prior injectionwas created for comparison purposes (n=31,229). The rate of postoperative infectionwas compared between injection cohorts and controls. RESULTS: The incidence of infection after THA at 3 months (2.41%; odds ratio, 1.9; P = .004) and 6 months (3.74%; odds ratio, 1.5; P < .019) was significantly higher in the patients who underwent hip injection within 3months before THA comparedwith controls. Therewas no significant difference in infection rates in patients who underwent THA between 3 and 6months or 6 and 12months after ipsilateral hip injection compared with controls. CONCLUSIONS: The present study demonstrates a significant increase in PJI in patients who underwent intraarticular hip injection within 3 months before THA. This association was not noted when THA was more than 3 months after injection. PMID- 26803712 TI - How to maintain equity and objectivity in assessing the communication skills in a large group of student nurses during a long examination session, using the Objective Structured Clinical Examination (OSCE). AB - BACKGROUND: While development, testing, and innovation of the Objective Structured Clinical Examination (OSCE) are common in the international literature, studies from the United States of America (USA), Australia, and the United Kingdom (UK) predominate. There is little known about OSCE use in European countries, such as Italy, where other than cost analysis, there is little reporting of OSCE use or validation. OBJECTIVES: This paper reports on one Italian initiative, which evaluated the equity and objectivity of the OSCE method of assessing communication skills. DESIGN: An OSCE method was used to assess the communication skills of first-year students of the Degree Course in Nursing. A method of simulation was implemented through role-playing with standardized patients. An observational method was used to collect data. PARTICIPANTS AND SETTINGS: Four hundred and twenty-one first-year undergraduate nursing students at one university site in Italy took part. METHODS: Ten examination sessions were carried out. The students' performances were assessed by two examiners who used a structured observation grid and conducted their assessment separately. A situation simulated by four nurses with experience as actors was used as the topic for the students' examination. RESULTS: Calculation of the daily rate of students who passed the examination revealed a random distribution over time. The nonparametric correlation indexes referring to the assessments and to the scores assigned by the two examiners proved statistically significant (P<=0.001). CONCLUSIONS: The study confirmed the validity of the OSCE method in ensuring equity and objectivity of communication skills assessment in a large population of nursing students for the purpose of certification throughout the duration of the examination. This has important implications for nurse education and practice as the extent to which OSCE approaches, while deemed objective, are culturally sensitive or valid and reliable across cultures is not clear. This is something that requires further research and examination in this field. PMID- 26803713 TI - Swyer-James-Macleod syndrome: a rare finding and important differential in the ED setting. PMID- 26803714 TI - Toxic shock syndrome due to methicillin-resistant Staphylococcus aureus infection after a pediatric scald burn. PMID- 26803715 TI - Validation of modified early warning score using serum lactate level in community acquired pneumonia patients. The National Early Warning Score-Lactate score. AB - STUDY OBJECTIVE: The aim of this study was to investigate the prognostic prediction power of a newly introduced early warning score modified by serum lactate level, the National Early Warning Score-Lactate (NEWS-L) score, among community-acquired pneumonia (CAP) patients. We also compared the NEWS-L score with the pneumonia severity index (PSI) and CURB-65. METHODS: We designed a retrospective observational study and collected data on confirmed adult CAP patients who visited the study hospital between October 2013 and September 2014. Variables relevant to, the NEWS-L score, PSI, and CURB-65 were extracted from electronic medical records. Survival status at hospital discharge was determined in the same manner. The NEWS-L score was calculated as NEWS-L=NEWS+serum lactate level (mmol/L). The NEWS-L was divided into quartiles. The ability to predict mortality was assessed through area under the receiver operating characteristic curve analysis and calibration analysis. RESULTS: A total of 553 patients were enrolled, and the inpatient mortality rate was 10.8% (n=60). Mortality rates increased incrementally in conjunction with the NEWS-L quartiles: first quartile, 2.2%; second quartile, 7.9%; third quartile, 9.6%; and fourth quartile, 23.9%. The area under the receiver operating characteristic curve of the NEWS-L score was 0.73 (95% confidence interval [CI], 0.66-0.80), which showed no significant difference from that of the PSI (0.68; 95% CI, 0.61-0.76; P=.28) and CURB-65 (0.66; 95% CI, 0.59-0.73; P=.06). CONCLUSIONS: The newly introduced early warning score modified by serum lactate level, NEWS-L score, was comparable to PSI and CURB-65, for predicting inpatient mortality among adult CAP patients. PMID- 26803717 TI - TEMPORARY REMOVAL: African emergency nursing curriculum: Development of a curriculum model. AB - The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 26803716 TI - A cross-sectional study of factors associated with birth weights of Norwegian beef calves. AB - A cross-sectional study was performed to evaluate factors which influence birth weights of beef suckler calves in Norway. Data were from a national beef cattle registry, and lifetime production data of cows slaughtered between January 2010 and January 2013 were included in the study population. The study population consisted of 20,541 cows and 53,819 calves. The analysis was performed on the subset of singleton calvings from which birth weights were recorded. The study sample consisted of 9903 cows with birth weights available for 29,294 calves. The mean birth weight was 43.47kg (95% CI 43.40; 43.53). Two multilevel linear regression models were built; the first was for all calves and included parity of dam as one of the explanatory variables (with herd and cow as random effects), the second model was for calves born to primiparous dams only where age of first calving was included as an explanatory variable (with a random herd effect). The multilevel regression models estimated that female calves were 2.3kg lighter than males (95% CI 2.2-2.4, P<0.001), that calves of Norwegian Red, Charolais, Aberdeen Angus and "Other" born in the western part of Norway were lighter than from all other regions, and that calving in the autumn yielded lighter offspring than calving other parts of the year. Furthermore, calves born from primiparous cows were heavier than calves from older cows. Herd explained a large proportion of the variation in birth weights (40% and 37%, in the full and heifer models, respectively), and both the herd and cow random effects were highly significant. In conclusion, birth weights of beef calves in the Norwegian Beef Cattle Recording System were influenced by sex of the calf, breed of the dam, parity, age at first calving, calving season, cow, herd and region. PMID- 26803718 TI - Characterizing substance use and mental health profiles of cigar, blunt, and non blunt marijuana users from the National Survey of Drug Use and Health. AB - BACKGROUND: Smoking marijuana in a cigar (blunt use) is gaining popularity in the U.S. Research suggests that blunt users differ from exclusive cigar or marijuana users on a variety of demographic and substance use factors. Misreporting of blunts and cigars is also common, particularly among young people, and may lead to inaccurate prevalence estimates. To determine subtype differences, this study investigated the prevalence and demographic, mental health, and substance use correlates of four mutually-exclusive groups of blunt, cigar, and marijuana past 30-day users (cigar-only, blunt-only, non-blunt marijuana, or dual cigar-blunt). METHOD: Data were analyzed from the 2013 National Survey of Drug Use and Health. RESULTS: In weighted multinomial logistic regression models, respondents who were younger, Black, and who had used tobacco, alcohol, or other drugs in the past 30 days had the highest odds of reporting blunt-only or dual cigar-blunt use. Those reporting blunt-only and dual cigar-blunt use also endorsed a greater number of marijuana and alcohol use disorder symptoms compared to those reporting cigar only and non-blunt marijuana use. Lower marijuana risk perceptions were associated with increased odds of marijuana use with or without blunts. Major depressive episode was uniquely associated with non-blunt marijuana use. With respect to misclassifiers, respondents who reported past 30-day blunt use but not past 30-day marijuana use were younger, Black, female, and had lower education and income. DISCUSSION: Those who report blunt-only and dual cigar-blunt use showed the most severe risk profiles. Communicating health consequences and risks of blunt use should be directed toward specific subgroups. PMID- 26803719 TI - Withdrawing inactive NRTIs in HIV-1 subjects with suppressed viraemia: a randomized trial. AB - BACKGROUND: Extensively pretreated subjects with virological failure (VF) may receive salvage regimens containing NRTIs with only residual or no activity. Once virological suppression is achieved, their contribution remains elusive. METHODS: This was a multicentre, randomized, prospective study. Subjects with at least one prior VF, HIV-1 RNA <50 copies/mL for >=6 months and receiving a regimen with at least two active drugs (one of them a boosted PI) were randomized 1:1 to stop (experimental arm) or maintain (control arm) NRTIs. EudraCT: 2012-000198-21. RESULTS: Ninety subjects were randomized (experimental, n = 45; and control, n = 45). The mean age was 50 years, 80% were male, the mean CD4+ cell count was 542 cells/mm(3) and the median number of prior VFs was 3. Seventy-four subjects (82%) harboured the mutation M184V/I and the median number of thymidine-associated mutations was 3 (IQR: 0-4). In the experimental arm, thirty-two (71%) subjects removed one NRTI and 13 (29%) subjects removed two. Twenty-two of 45 (49%) discontinued tenofovir disoproxil fumarate. Forty-one of 45 (91.1%, experimental arm) and 44 of 45 (97.8%, control arm) had HIV-1 RNA <50 copies/mL at 48 weeks (difference: -6.7%; 95% CI: -17.4, 4.1). In a post-hoc analysis allowing NRTI reintroduction, efficacy rates were 95.6% and 97.8%, respectively (difference: 2.2%; 95% CI: -7.2, 2.7). Rates of discontinuation at 48 weeks were 2% in both arms. One subject developed a late VF with resistance selection. CONCLUSIONS: In patients receiving a successful multidrug salvage regimen with at least two active drugs (one a boosted PI), the withdrawal of inactive NRTIs was safe, rates of VF were low and drug resistance was uncommon at 48 weeks in this small study. This strategy could potentially prevent long-term toxicities, reduce the number of drugs and reduce costs if non-inferiority was met in a fully powered trial. PMID- 26803720 TI - Diversity of STs, plasmids and ESBL genes among Escherichia coli from humans, animals and food in Germany, the Netherlands and the UK. AB - OBJECTIVES: This study aimed to compare ESBL-producing Escherichia coli causing infections in humans with infecting or commensal isolates from animals and isolates from food of animal origin in terms of the strain types, the ESBL gene present and the plasmids that carry the respective ESBL genes. METHODS: A collection of 353 ESBL-positive E. coli isolates from the UK, the Netherlands and Germany were studied by MLST and ESBL genes were identified. Characterization of ESBL gene-carrying plasmids was performed using PCR-based replicon typing. Moreover, IncI1-Igamma and IncN plasmids were characterized by plasmid MLST. RESULTS: The ESBL-producing E. coli represented 158 different STs with ST131, ST10 and ST88 being the most common. Overall, blaCTX-M-1 was the most frequently detected ESBL gene, followed by blaCTX-M-15, which was the most common ESBL gene in the human isolates. The most common plasmid replicon type overall was IncI1 Igamma followed by multiple IncF replicons. CONCLUSIONS: ESBL genes were present in a wide variety of E. coli STs. IncI1-Igamma plasmids that carried the blaCTX-M 1 gene were widely disseminated amongst STs in isolates from animals and humans, whereas other plasmids and STs appeared to be more restricted to isolates from specific hosts. PMID- 26803721 TI - Asthma and Risk of Stroke: A Systematic Review and Meta-analysis. AB - BACKGROUND: Several studies have suggested that asthma is associated with an increased risk of stroke. However, the results are inconsistent. The aim of this study is to investigate the relation of asthma and the risk of stroke through a systematic review and meta-analysis of published research. METHODS: Pertinent studies were identified by a search of the PubMed and the Web of Science databases to June 2015. Study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using fixed-effect or random-effect models when appropriate. Associations were tested in subgroups representing different participants and study characteristics. Publication bias was assessed with Egger's test. RESULTS: Five articles comprising 524,637 participants and 6031 stroke cases were eligible for inclusion. Asthma was associated significantly with increased risk of stroke, and the pooled HR was 1.32 (95% CI: 1.13, 1.54, I(2)=80.4%). Subgroup analyses revealed that the association between asthma and stroke risk was stronger among female patients (HR = 1.42, 95% CI: 1.15-1.76) and prospective cohort study design (HR = 1.52, 95% CI: 1.21-1.91). CONCLUSION: Asthma is associated with a significantly increased risk of stroke. This finding may have clinical and public health importance. PMID- 26803722 TI - Drops in Barometric Pressure Are Associated with Deep Intracerebral Hemorrhage. AB - BACKGROUND AND PURPOSE: The objective of this study is to assess the effects of changes in barometric pressure and outdoor temperature on the incidence of different subtypes of intracerebral hemorrhage (ICH). METHODS: Consecutive patients with primary supratentorial ICH were included. All patients resided in the same geographic area. We compared patients with subcortical ICH to those with cortical ICH. Meteorological data were continuously accrued. High-risk ICH days were defined as those on which 1 or more patients with ICH were admitted and compared to non-high-risk days. We analyzed the relationship between spontaneous ICH location and averaged daily atmospheric pressures and temperatures. RESULTS: We included 206 patients (147 with deep ICH and 59 with lobar ICH). Patients with deep ICH were younger (P < .001), more often had histories of diabetes, smoking and previous lacunar strokes, and were more often male (P < .01 for all). Drops in mean air pressure 2 days prior to the ictus were associated with deep but not lobar ICH (P = .006). Deep ICH clustered during February months in parallel with larger changes in barometric pressures (P < .001). CONCLUSIONS: Drops in daily atmospheric pressures were associated with deep but not cortical ICH, suggesting a link to hypertensive etiology. Changes in barometric pressures were also associated with higher monthly frequencies of ICH. PMID- 26803723 TI - Arterial Stiffness, Distensibility, and Strain in Asthmatic Children. AB - BACKGROUND: We hypothesized that since asthma is a chronic inflammatory disease, it could lead to the early development of atherosclerosis in childhood-onset asthma. The aim of this study was to investigate arterial stiffness, distensibility, and strain of different peripheral arteries, the parameters of which can be used to detect atherosclerosis in asthmatic children. MATERIAL/METHODS: We studied 22 pediatric patients with asthma and 18 healthy children. Fasting blood glucose and cholesterol levels were evaluated to exclude children with diabetes and hyperlipidemia, which are risk factors for atherosclerosis. Renal, carotid, and brachial arteries diameters were measured. Using the measured data, stiffness, distensibility, and strain of the arteries of all children were calculated. RESULTS: Pulse pressure, systolic and diastolic blood pressure, heart rate, cholesterols, and glucose levels of the obese individuals were similar to the controls. In carotid arteries there were no statistical differences regarding stiffness, distensibility, and strain. According to multiple ANCOVA analysis, distensibility and strain of right and left brachial arteries and right renal artery were higher, whereas right renal artery stiffness was lower in asthmatic children than in controls. Approximately one-fifth of the change in the left and right brachial arteries and right renal artery distensibility and strain and a small portion of the change in the right renal artery stiffness were associated with asthma. In contrast, left renal artery distensibility, strain, and stiffness were not associated with asthma. CONCLUSIONS: Peripheral arteries had higher distensibility and strain, and lower stiffness in asthmatic children than in controls. PMID- 26803724 TI - Rowell's syndrome: The two sides of the truth. PMID- 26803725 TI - Lack of association between TOR1A and THAP1 mutations and sporadic adult-onset primary focal dystonia in a Chinese population. AB - OBJECTIVE: TOR1A (torsin family 1, member A) and THAP1 (THAP domain containing, apoptosis associated protein 1) are two candidate genes that have been reported to be linked to adult-onset primary dystonia. However, the overall results have been inconsistent, likely because primary dystonia may have subtype-specific genetic risk factors. The aim of our study was to assess the association of TOR1A and THAP1 with adult-onset primary focal dystonia (AOPFD), the most common subtype of primary dystonia. METHODS: A total of 248 subjects, comprising 117 AOPFD patients and 131 healthy controls, were included in our study. All coding exons of TOR1A and THAP1 were initially analyzed in the 117 patients. Subsequently, we investigated the association of two common TOR1A variants (rs2296793, rs1801968) with AOPFD in a Chinese population (117 patients versus 131 controls) and performed a pooled analysis by combining our data with previously published data. RESULTS: No mutation of TOR1A and THAP1 was found other than two TOR1A variants (rs2296793, rs1801968), which have been previously reported in AOPFD patients. There were no statistically significant differences in the minor allele frequency (MAF) and genotype frequency between AOPFD and controls in our Chinese population (P>0.05). This result was confirmed by pooled analysis of multi-ethnic groups. CONCLUSION: Our study suggested that there might not be an association between TOR1A or THAP1 and patients with AOPFD. PMID- 26803726 TI - Stratification of predictive factors to assess resectability and surgical outcome in clinoidal meningioma. AB - OBJECTIVE: Meningiomas of the clinoidal region pose significant surgical challenges due to their close proximity and intimate relation with surrounding critical neurovascular structures. Our aim was to describe our institution's experience with the management of clinoidal meningiomas, identify predictive factors and develop a comprehensive grading system to assess the extent of resection. METHODS: The medical records of 36 consecutive patients underwent surgery from 1995 to 2015 with clinoidal meningiomas were retrospectively reviewed. Using selected clinical features and tumor characteristics, a grading scale was devised and utilized to assess a degree of tumor resectability. The factors included: preoperative visual status(no visual loss=0, visual loss=1), tumor volume: small (<13.5 cm(3)=1), moderate (13.5-30 cm(3)=2), and large (>30 cm(3)=3),relationship with the internal carotid artery (no displacement=0, displacement=1, encasement=2, stenosis=3 and bilateral involvement=4) tumor extension into the cavernous sinus (yes=1, no=0) and invasion into the optic canal (yes=1, no=0), (defined as tumor beyond the falciform ligament). A grading system was designed using the total scores (10) in this classification and separating patients into two groups: group 1 with scores of 5 or less, group 2 with scores more than 5. RESULTS: The patients mean age at the time of intervention was 61 years. The tumor involved the cavernous sinus in 38.9% of patients and invaded the optic canal in 36% of cases. The patient presented with visual impairment in 89% of cases. Vision improved in 28% and remained stable in 63% of cases. The mean volume of a tumor was 16.99 cm(3). The most common approach involved pterional with or without anterior clinoidectomy. After stratification, group 1 consisting of 22 patients and in group 2, 14 patients. Gross total resection (Simpson Grade I or II) was achieved in 75% of surgeries and subtotal and partial resections were achieved in 25% of cases. Group 1 patients had higher gross total resection rate than group 2 (p=0.009). Only optic canal involvement was significantly associated with the extent of resectabilty in a univariate analysis (p=0.03). Four patients developed tumor recurrence with median recurrence duration of 89 months (53-204 months). Three patients underwent GKRS and one patient underwent repeat surgery at the time of recurrence. CONCLUSIONS: A grading system can be employed in patients who present with clinoidal meningiomas and serve as an aid in planning an appropriate treatment strategy and establishing the prognosis. Radical resection can be planned in patients with favorable tumor criteria (groups 1) while a less aggressive surgical approach followed by stereotactic radiosurgery may be better suited for patients with less favorable tumor characteristics (group 2). PMID- 26803727 TI - Small is Plentiful. AB - Rhizobia are legume symbionts that arise through horizontal transfer of symbiotic genes among soil bacteria. A recent study shows that these transfers occur frequently at a micro-scale, leading to unexpected rhizobial diversity and emergence of symbiovars within species. This confirms the disconnection between function and taxonomy in bacterial communities. PMID- 26803728 TI - Local Control of Aldosterone Production and Primary Aldosteronism. AB - Primary aldosteronism (PA) is caused by excessive production of aldosterone by the adrenal cortex and is determined by a benign aldosterone-producing adenoma (APA) in a significant proportion of cases. Local mechanisms, as opposed to circulatory ones, that control aldosterone production in the adrenal cortex are particularly relevant in the physiopathological setting and in the pathogenesis of PA. A breakthrough in our understanding of the pathogenetic mechanisms in APA has been the identification of somatic mutations in genes controlling membrane potential and intracellular calcium concentrations. However, recent data show that the processes of nodule formation and aldosterone hypersecretion can be dissociated in pathological adrenals and suggest a model envisaging different molecular events for the pathogenesis of APA. PMID- 26803729 TI - XBP1: A Pivotal Transcriptional Regulator of Glucose and Lipid Metabolism. AB - X-box binding protein 1 (XBP1) is a major, well-conserved component of the unfolded protein response (UPR) that is crucial for glucose homeostasis and lipid metabolism. Metabolic dysfunction has been associated with XBP1 transcriptional activity. Recently, compounds selectively targeting the IRE1alpha-XBP1 pathway have emerged as a potential approach for treatment of metabolic diseases. PMID- 26803730 TI - Does perfluorooctane sulfonate (PFOS) act as chemosensitizer in zebrafish embryos? AB - Earlier studies have shown that perfluorooctane sulfonate (PFOS) increases the toxicity of other chemicals by enhancing their uptake by cells and tissues. The present study aimed at testing whether the underlying mechanism of enhanced uptake of chemicals by zebrafish (Danio rerio) embryos in the presence of PFOS is by interference of this compound with the cellular efflux transporter Abcb4. Modifications of uptake/clearance and toxicity of two Abcb4 substrates, the fluorescent dye rhodamine B (RhB) and vinblastine, by PFOS were evaluated using 24 and 48h post-fertilization (hpf) embryos. Upon 90min exposure of 24hpf embryos to 1MUM RhB and different PFOS concentrations (3-300MUM) accumulation of RhB in zebrafish was increased by up to 11.9-fold compared to controls, whereas RhB increases in verapamil treatments were 1.7-fold. Co-administration of PFOS and vinblastine in exposures from 0 to 48hpf resulted in higher vinblastine-caused mortalities in zebrafish embryos indicating increased uptake of this compound. Interference of PFOS with zebrafish Abcb4 activity was further studied using recombinant protein obtained with the baculovirus expression system. PFOS lead to a concentration-dependent decrease of the verapamil-stimulated Abcb4 ATPase activity; at higher PFOS concentrations (250, 500MUM), also the basal ATPase activity was lowered indicating PFOS to be an Abcb4 inhibitor. In exposures of 48hpf embryos to a very high RhB concentration (200MUM), accumulation of RhB in embryo tissue and adsorption to the chorion were increased in the presence of 50 or 100MUM PFOS. In conclusion, the results indicate that PFOS acts as inhibitor of zebrafish Abcb4; however, the exceptionally large PFOS-caused effect amplitude of RhB accumulation in the 1MUM RhB experiments and the clear PFOS effects in the experiments with 200MUM RhB suggest that an additional mechanism appears to be responsible for the potential of PFOS to enhance uptake of Abcb4 substrates. PMID- 26803731 TI - Changing climate and nutrient transfers: Evidence from high temporal resolution concentration-flow dynamics in headwater catchments. AB - We hypothesise that climate change, together with intensive agricultural systems, will increase the transfer of pollutants from land to water and impact on stream health. This study builds, for the first time, an integrated assessment of nutrient transfers, bringing together a) high-frequency data from the outlets of two surface water-dominated, headwater (~10km(2)) agricultural catchments, b) event-by-event analysis of nutrient transfers, c) concentration duration curves for comparison with EU Water Framework Directive water quality targets, d) event analysis of location-specific, sub-daily rainfall projections (UKCP, 2009), and e) a linear model relating storm rainfall to phosphorus load. These components, in combination, bring innovation and new insight into the estimation of future phosphorus transfers, which was not available from individual components. The data demonstrated two features of particular concern for climate change impacts. Firstly, the bulk of the suspended sediment and total phosphorus (TP) load (greater than 90% and 80% respectively) was transferred during the highest discharge events. The linear model of rainfall-driven TP transfers estimated that, with the projected increase in winter rainfall (+8% to +17% in the catchments by 2050s), annual event loads might increase by around 9% on average, if agricultural practices remain unchanged. Secondly, events following dry periods of several weeks, particularly in summer, were responsible for high concentrations of phosphorus, but relatively low loads. The high concentrations, associated with low flow, could become more frequent or last longer in the future, with a corresponding increase in the length of time that threshold concentrations (e.g. for water quality status) are exceeded. The results suggest that in order to build resilience in stream health and help mitigate potential increases in diffuse agricultural water pollution due to climate change, land management practices should target controllable risk factors, such as soil nutrient status, soil condition and crop cover. PMID- 26803732 TI - Effects of shisha smoking on carbon monoxide and PM2.5 concentrations in the indoor and outdoor microenvironment of shisha premises. AB - There has been significant rise in shisha premises in the United Kingdom with an unsubstantiated belief that shisha smoking is harmless and relatively safe. This study aimed to assess the public health situation by evaluating the extent of shisha environmental tobacco smoke (ETS) exposure among those that work in, and are customers of shisha businesses. Concentrations of several ETS pollutants such as carbon monoxide (CO) and particulate matter with a diameter of less than 2.5MUm (PM2.5) in shisha premises were measured using real-time sensors inside and outside twelve shisha premises and at 5 pubs/restaurants where smoking is prohibited. Mean concentration of CO (7.3+/-2.4mg/m(3)) and PM2.5 (287+/ 233MUg/m(3)) inside active shisha premises was higher than concentrations measured within the vicinity of the shisha premises (CO: 0.9+/-0.7mg/m(3) and PM2.5: 34+/-14MUg/m(3)) and strongly correlated (PM2.5 R=0.957). Concentrations were higher than indoor concentrations in pubs and restaurants where smoking is not permitted under UK law. The number of shisha pipes was a strong predictor of the PM2.5 concentrations. The study also assessed the risk perception within patrons and managers, with only 25% being aware of the risks associated to shisha smoking. The study identifies owners, employees and consumers within active shisha premises being exposed to concentrations of CO and PM2.5 at levels considered hazardous to human health. The results and outcome of this research serve as a basis to influence a discussion around the need of developing specific policies to protect consumers and employees of such premises. PMID- 26803733 TI - Characteristics, source apportionment and reactivity of ambient volatile organic compounds at Dinghu Mountain in Guangdong Province, China. AB - Volatile organic compounds (VOCs) play a very important role in the formation of ozone and secondary organic aerosols. The concentrations, compositions, and variability of VOCs were measured from 2005 to 2008 at Dinghu Mountain Forest Ecosystem Research Station, a remote station in Southeast China. Weekly samples were collected in the Dinghu Mountain area and were analysed via gas chromatography-mass spectrometry. The results revealed that the total VOC concentrations decreased continuously and that the dominant VOC components were alkanes (43%) and aromatics (33%), followed by halo-hydrocarbons (12%) and alkenes (12%). The general trend of seasonal variation indicated higher concentrations in spring and lower concentrations in summer. The positive matrix factorization model was used to identify the sources of the VOCs. Seven sources were resolved by the PMF model: (1) vehicular emissions, which contributed 25% of the total VOC concentration; (2) industrial sources and regional transportation, contributing 17%; (3) paint solvent use, contributing 17%; (4) fuel evaporation, contributing 13%; (5) stationary combustion sources, contributing 12%; (6) biogenic emissions, contributing 10%; and aged VOCs, contributing only 6%. The HYSPLIT model was used to analyse the effect of pollutant transport, and the results indicated that the transport of pollutants from cities cannot be ignored. Finally, the OH radical loss rates and ozone formation potentials (OFPs) were calculated, and the results indicated isoprene to have the highest OH radical loss rate and toluene to be the largest contributor to the OFP at the Dinghu Mountain site. PMID- 26803734 TI - Selection of focal earthworm species as non-target soil organisms for environmental risk assessment of genetically modified plants. AB - By means of a literature survey, earthworm species of significant relevance for soil functions in different biogeographical regions of Europe (Atlantic, Boreal, Mediterranean) were identified. These focal earthworm species, defined here according to the EFSA Guidance Document on the environmental risk assessment (ERA) of genetically modified plants, are typical for arable soils under crop rotations with maize and/or potatoes within the three regions represented by Ireland, Sweden and Spain, respectively. Focal earthworm species were selected following a matrix of four steps: Identification of functional groups, categorization of non-target species, ranking species on ecological criteria, and final selection of focal species. They are recommended as appropriate non-target organisms to assess environmental risks of genetically modified (GM) crops; in this case maize and potatoes. In total, 44 literature sources on earthworms in arable cropping systems including maize or potato from Ireland, Sweden and Spain were collected, which present information on species diversity, individual density and specific relevance for soil functions. By means of condensed literature data, those species were identified which (i) play an important functional role in respective soil systems, (ii) are well adapted to the biogeographical regions, (iii) are expected to occur in high abundances under cultivation of maize or potato and (iv) fulfill the requirements for an ERA test system based on life-history traits. First, primary and secondary decomposers were identified as functional groups being exposed to the GM crops. In a second step, anecic and endogeic species were categorized as potential species. In step three, eight anecic and endogeic earthworm species belonging to the family Lumbricidae were ranked as relevant species: Aporrectodea caliginosa, Aporrectodea rosea, Aporrectodea longa, Allolobophora chlorotica, Lumbricus terrestris, Lumbricus friendi, Octodrilus complanatus and Octolasion cyaneum. Five out of these eight species are relevant for each biogeographical region with an overlap in the species. Finally, the earthworm species Ap. caliginosa (endogeic, secondary decomposer) and L. terrestris (anecic, primary decomposer) were selected as focal species. In the Mediterranean region L. terrestris may be substituted by the more relevant anecic species L. friendi. The selected focal species are recommended to be included in a standardized laboratory ERA test system based on life-history traits. PMID- 26803735 TI - Organic amendments for improving biomass production and metal yield of Ni hyperaccumulating plants. AB - Ni phytomining is a promising technology for Ni recovery from low-grade ores such as ultramafic soils. Metal-hyperaccumulators are good candidates for phytomining due to their extraordinary capacity for Ni accumulation. However, many of these plants produce a low biomass, which makes the use of agronomic techniques for improving their growth necessary. In this study, the Ni hyperaccumulators Alyssum serpyllifolium ssp. lusitanicum, A. serpyllifolium ssp. malacitanum, Alyssum bertolonii and Noccaea goesingense were evaluated for their Ni phytoextraction efficiency from a Ni-rich serpentine soil. Effects of soil inorganic fertilisation (100:100:125kgNPKha(-1)) and soil organic amendment addition (2.5, 5 or 10% compost) on plant growth and Ni accumulation were determined. All soil treatments greatly improved plant growth, but the highest biomass production was generally found after addition of 2.5 or 5% compost (w/w). The most pronounced beneficial effects were observed for N. goesingense. Total Ni phytoextracted from soils was significantly improved using both soil treatments (inorganic and organic), despite the decrease observed in soil Ni availability and shoot Ni concentrations in compost-amended soils. The most promising results were found using intermediate amount of compost, indicating that these types of organic wastes can be incorporated into phytomining systems. PMID- 26803737 TI - Evaluating the trade-off between food and timber resulting from the conversion of Miombo forests to agricultural land in Angola using multi-temporal Landsat data. AB - The repopulation of abandoned areas in Angola after 27years of civil war led to a fast and extensive expansion of agricultural fields to meet the rising food demand. Yet, the increase in crop production at the expense of natural resources carries an inherent potential for conflicts since the demand for timber and wood extraction are also supposed to rise. We use the concept of ecosystem services to evaluate the trade-off between food and woody biomass. Our study area is located in central Angola, in the highlands of the upper Okavango catchment. We used Landsat data (spatial resolution: 30*30m) with a bi-temporal and multi-seasonal change detection approach for five time steps between 1989 and 2013 to estimate the conversion area from woodland to agriculture. Overall accuracy is 95%, user's accuracy varies from 89-95% and producer's accuracy ranges between 92-99%. To quantify the trade-off between woody biomass and the amount of food, this information was combined with indicator values and we furthermore assessed biomass regrowth on fallows. Our results reveal a constant rise in agricultural expansion from 1989-2013 with the mean annual deforestation rate increasing from roughly 5300ha up to about 12,000ha. Overall, 5.6% of the forested areas were converted to agriculture, whereas the FAO states a national deforestation rate for Angola of 5% from 1990-2010 (FAO, 2010). In the last time step 961,000t per year of woodland were cleared to potentially produce 1240t per year of maize. Current global agro-economical projections forecast increasing pressure on tropical dry forests from large-scale agriculture schemes (Gasparri et al., 2015; Searchinger and Heimlich, 2015). Our study underlines the importance of considering subsistence-related change processes, which may contribute significantly to negative effects associated with deforestation and degradation of these forest ecosystems. PMID- 26803736 TI - Iron sulfide attenuates the methanogenic toxicity of elemental copper and zinc oxide nanoparticles and their soluble metal ion analogs. AB - Elemental copper (Cu(0)) and zinc oxide (ZnO) nanoparticle (NP) toxicity to methanogens has been attributed to the release of soluble metal ions. Iron sulfide (FeS) partially controls the soluble concentration of heavy metals and their toxicity in aquatic environments. Heavy metals displace the Fe from FeS forming poorly soluble metal sulfides in the FeS matrix. Therefore, FeS may be expected to attenuate the NP toxicity. This work assessed FeS as an attenuator of the methanogenic toxicity of Cu(0) and ZnO NPs and their soluble salt analogs. The toxicity attenuation capacity of fine (25-75MUm) and coarse (500 to 1200MUm) preparations of FeS (FeS-f and FeS-c respectively) was tested in the presence of highly inhibitory concentrations of CuCl2, ZnCl2 Cu(0) and ZnO NPs. FeS-f attenuated methanogenic toxicity better than FeS-c. The results revealed that 2.5* less FeS-f than FeS-c was required to recover the methanogenic activity to 50% (activity normalized to uninhibited controls). The results also indicated that a molar FeS-f/Cu(0) NP, FeS-f/ZnO NP, FeS-f/ZnCl2, and FeS-f/CuCl2 ratio of 2.14, 2.14, 4.28, and 8.56 respectively, was necessary to recover the methanogenic activity to >75%. Displacement experiments demonstrated that CuCl2 and ZnCl2 partially displaced Fe from FeS. As a whole, the results indicate that not all the sulfide in FeS was readily available to react with the soluble Cu and Zn ions which may explain the need for a large stoichiometric excess of FeS to highly attenuate Cu and Zn toxicity. Overall, this study provides evidence that FeS attenuates the toxicity caused by Cu(0) and ZnO NPs and their soluble ion analogs to methanogens. PMID- 26803738 TI - Exposure Risk of Rural Residents to Copper in the Le'an River Basin, Jiangxi Province, China. AB - The Dexing copper (Cu) mining zone in Jiangxi Province produces China's highest annual copper output, and the mineral waste residue and wastewater associated with ore processing are responsible for the Cu contamination of agricultural soil and food produced in the Le'an River Basin. We studied the dietary Cu intake from various foods, and the induced non-carcinogenic risk in rural residents from Dexing, Poyang, and Leping Counties situated along the Le'an River. Different food types based on the local dietary habits and agricultural soils were collected, and their Cu contents were analyzed. The Monte Carlo model was used to simulate the dietary chronic daily intake of Cu (CDICu) and its non-carcinogenic risk in four subgroups (children, adolescents, adults, and seniors). A consistently decreasing trend in the Cu levels in agricultural soil and two local food types (vegetables and eggs) was found with increasing distance downstream from the mining zone from Dexing to Poyang, whereas this trend was not observed in other food types. The order of CDICu among the three counties was Dexing > Leping > Poyang, and the order among the four subgroups was children > adolescents > adults = seniors. The two major contributors to the total CDICu were vegetables and rice. Rural residents from Dexing County had the highest proportion of people with a hazard quotient (HQ) >1 (i.e., 79%), followed by Leping (60%) and Poyang (48%). For Dexing, ~98% of the children living in rural areas displayed HQ >1, compared with 97% in Leping and 85% in Poyang. Our results indicated the importance of the potential effects of Cu on the health of the local young population and the need to address such effects. PMID- 26803739 TI - Do you reckon it's normally distributed? PMID- 26803740 TI - Flow regulation manipulates contemporary seasonal sedimentary dynamics in the reservoir fluctuation zone of the Three Gorges Reservoir, China. AB - Since the launch of the Three Gorges Dam on the Yangtze River, a distinctive reservoir fluctuation zone has been created and significantly modified by regular dam operations. Sediment redistribution within this artificial landscape differs substantially from that in natural fluvial riparian zones, due to a specific hydrological regime comprising steps of water impoundment with increasing magnitudes and seasonal water level fluctuation holding a range of sediment fluxes. This study reinterpreted post-dam sedimentary dynamics in the reservoir fluctuation zone by stratigraphy determination of a 345-cm long sediment core, and related it to impact of the hydrological regime. Seasonality in absolute grain-size composition of suspended sediment was applied as a methodological basis for stratigraphic differentiation. Sedimentary laminations with relatively higher proportions of sandy fractions were ascribed to sedimentation during the dry season when proximal subsurface bank erosion dominates source contributions, while stratigraphy with a lower proportion of sandy fractions is possibly contributed by sedimentation during the wet season when distal upstream surface erosion prevails. Chronology determination revealed non-linear and high annual sedimentation rates ranging from 21.7 to 152.1cm/yr. Although channel geomorphology may primarily determine the spatial extent of sedimentation, seasonal sedimentary dynamics was predominantly governed by the frequency, magnitude, and duration of flooding. Summer inundation by natural floods with enhanced sediment loads produced from upstream basins induced higher sedimentation rates than water impoundment during the dry season when distal sediment supply was limited. We thus conclude that flow regulation manipulates contemporary seasonal sedimentary dynamics in the reservoir fluctuation zone, though little impact on total sediment retention rate was detected. Ongoing reductions in flow and sediment supply under human disturbance may have profound implications in affecting sedimentary equilibrium in the reservoir fluctuation zone. The results herein provide insights of how big dams have disrupted the sediment conveyance processes of large scale fluvial systems. PMID- 26803741 TI - Controls of evaporative irrigation return flows in comparison to seawater intrusion in coastal karstic aquifers in northern Sri Lanka: Evidence from solutes and stable isotopes. AB - Groundwater in Miocene karstic aquifers in the Jaffna Peninsula of Sri Lanka is an important resource since no other fresh water sources are available in the region. The subsurface is characterized by highly productive limestone aquifers that are used for drinking and agriculture purposes. A comprehensive hydrogeochemical study was carried out to reveal the processes affecting the groundwater quality in this region. Major and trace element composition and environmental isotope ratios of oxygen and hydrogen (delta(18)OH2O and delta(2)HH2O) were determined in 35 groundwater samples for this investigation. The ion abundance of groundwater in the region was characterized by an anion sequence order with HCO3->Cl->SO4->NO3-. For cations, average Na(+)+K(+) contents in groundwater exceeded those of Ca(2+)+Mg(2+) in most cases. Ionic relationships of major solutes indicated open system calcite dissolution while seawater intrusions are also evident but only close to the coast. The solute contents are enriched by agricultural irrigation returns and associated evaporation. This was confirmed by the stable isotope composition of groundwater that deviated from the local meteoric water line (LMWL) and formed its own regression line denoted as the local evaporation line (LEL). The latter can be described by delta(2)HH2O=5.8*delta(18)OH2O -- 2.9. Increased contents of nitrate-N (up to 5mg/L), sulfate (up to 430mg/L) and fluoride (up to 1.5mg/L) provided evidences for anthropogenic inputs of solutes, most likely from agriculture activities. Among trace elements Ba, Sr, As and Se levels in the Jaffna groundwater were higher compared to that of the dry zone metamorphic aquifers in Sri Lanka. Solute geochemistry and stable isotope evidences from the region indicates that groundwater in the area is mainly derived from local modern precipitation but modified heavily by progressive evaporative concentration rather than seawater intrusion. PMID- 26803742 TI - Possibility of sludge conditioning and dewatering with rice husk biochar modified by ferric chloride. AB - Rice husk biochar modified by FeCl3 (MRB-Fe) was used to enhance sludge dewaterability in this study. MRB-Fe preparation conditions and dosage were optimized. Mechanisms of MRB-Fe improving sludge dewaterability were investigated. The optimal modification conditions were: FeCl3 concentration, 3mol/L; ultrasound time, 1h. The optimal MRB-Fe dosage was 60% DS. Compared with raw sludge, the sludge specific resistance to filtration (SRF) decreased by 97.9%, the moisture content of sludge cake decreased from 96.7% to 77.9% for 6min dewatering through vacuum filtration under 0.03MPa, the SV30% decreased from 96% to 60%, and the net sludge solids yield (YN) increased by 28 times. Positive charge from iron species on MRB-Fe surface counteracted negative charge of sludge flocs to promote sludge settleability and dewaterability. Meanwhile, MRB-Fe kept a certain skeleton structure in sludge cake, making the moisture pass through easily. Using MRB-Fe, therefore, for sludge conditioning and dewatering is promising. PMID- 26803743 TI - Inclusion of Sarcopenia Outperforms the Modified Frailty Index in Predicting 1 Year Mortality among 1,326 Patients Undergoing Gastrointestinal Surgery for a Malignant Indication. AB - BACKGROUND: Although it is a useful metric for preoperative risk stratification, frailty can be difficult to identify in patients before surgery. We sought to develop a preoperative frailty-risk model combining sarcopenia with clinical parameters to predict 1-year mortality using a cohort of patients undergoing gastrointestinal cancer surgery. STUDY DESIGN: We identified 1,326 patients undergoing hepatobiliary, pancreatic, or colorectal surgery between 2011 and 2014. Sarcopenia defined by psoas density was measured using preoperative cross sectional imaging. Multivariable Cox regression analysis was performed to identify preoperative risk factors associated with 1-year mortality and used to develop a preoperative risk-stratification score. RESULTS: Among all patients identified, 640 (48.3%) patients underwent pancreatic surgery, 347 (26.2%) underwent a hepatobiliary procedure, and 339 (25.5%) a colorectal procedure. Using sex-specific cut-offs, 398 (30.0%) patients were categorized as sarcopenic. Sarcopenic patients were more likely to develop postoperative complications vs non-sarcopenic patients (odds ratio [OR] 1.80, 95% CI 1.42 to 2.29; p < 0.001). Overall 1-year mortality was 9.4%. On multivariable analysis, independent risk factors for 1-year mortality included increasing age (65 to 75 years: [hazard ratio (HR) 1.81, 95% CI 1.05 to 3.14] greater than 75 years [HR 2.79, 95% CI 1.55 to 5.02]), preoperative anemia hemoglobin < 12.5 g/dL (HR 1.68, 95% CI 1.17 to 2.40), and preoperative sarcopenia (HR 1.98, 95% CI 1.36 to 2.88; all p < 0.05). Using these variables, a 28-point weighed composite score was able to stratify patients by their risk for mortality 1 year after surgery (C-statistic = 0.70). The proposed score outperformed other indices of frailty including the modified Frailty Index (C-statistic = 0.55) and the Eastern Cooperative Oncology Group (ECOG) performance score (C-statistic = 0.57) (both p < 0.05). CONCLUSION: Sarcopenia was combined with clinical factors to generate a composite risk-score that can be used to identify frail patients at greatest risk for 1-year mortality after gastrointestinal cancer surgery. PMID- 26803744 TI - Effect of Tualang honey on the anastomotic wound healing in large bowel anastomosis in rats-A randomized controlled trial. AB - BACKGROUND: Honey has long been used for the treatment of number of ailments and diseases including surgical wounds. Current study evaluates the effectiveness of Tualang honey (TH) for large bowel anastomotic healing in Wistar rats. METHODS: Thirty male Wistar rats were given a 3 centimeter infra-umbilical laparotomy wound, in'flicted on their abdomen. The colonic transection was performed at 5 cm distal to caecum, with end to end anastomosis of colon segment. They were divided into two groups. Group I was fed with standard rat chow and water. Meanwhile, Group II apart from standard feed, was also given TH 1.0 g/kg every morning until day seven post operatively. Afterwards, anastomotic bursting pressures were measured and histopathological examination on the anastomosis line was performed with light microscopes. The data from two groups were analyzed by Independent paired t test for continuous variables. RESULTS: It was found that the tensile strength of colon anastomosis (95 % CI; p = <0.001) and the histopathological study including fibroblast count (p = <0.001) and inflammatory cells (p = 0.002) showed statistically significant difference in the favor of TH-treated group. Meanwhile, neovascularization formation was not statistically significant (p = 0.807); however, the overall count in the TH group was high. CONCLUSION: Oral treatment with TH enhances anastomotic wound healing by increasing the number of fibroblasts and by decreasing inflammatory cells leading towards increased wound strength. PMID- 26803745 TI - Torsin ATPases: structural insights and functional perspectives. AB - Torsin ATPases are the only members of the AAA+ ATPase family that localize to the endoplasmic reticulum and contiguous perinuclear space. Accordingly, they are well positioned to perform essential work in these compartments, but their precise functions remain elusive. Recent studies have deciphered an unusual ATPase activation mechanism relying on Torsin-associated transmembrane cofactors, LAP1 or LULL1. These findings profoundly change our molecular view of the Torsin machinery and rationalize several human mutations in TorsinA or LAP1 leading to congenital disorders, symptoms of which have recently been recapitulated in mouse models. Here, we review these recent advances in the Torsin field and discuss the most pressing questions in relation to nuclear envelope dynamics. PMID- 26803746 TI - Effects of postoperative administration of celecoxib on pain management in patients after total knee arthroplasty: study protocol for an open-label randomized controlled trial. AB - BACKGROUND: Multimodal analgesia is achieved by combining different analgesics and different methods of analgesic administration, synergistically providing superior pain relief when compared with conventional analgesia. Multimodal analgesia can also result in reductions in the side effects and complications of analgesia, thereby improving patient safety. Preventive analgesia, treatment before initiation of the surgical procedure, has a potential to be more effective in reducing pain sensitization than treatment initiated after surgery. Multimodal analgesia that includes prophylactic administration of selective cyclooxygenase-2 (COX-2) inhibitors can improve postoperative pain and reduce opioid analgesic consumption after total knee arthroplasty (TKA). However COX-2 inhibitors are not approved for use as preventive analgesia in Japan. Thus, assessing the effectiveness of COX-2 inhibitors during the early postoperative period is important to establish clinical practice guidelines in Japan. This study was designed to examine the effects of celecoxib administration immediately after surgery, in addition to multimodal analgesia, on postoperative pain management after TKA. METHODS/DESIGN: This randomized, prospective, open-label controlled study will include 120 patients undergoing unilateral TKA. All patients will routinely receive single injections of femoral and sciatic nerve blocks, along with postoperative patient-controlled analgesia (PCA) with fentanyl. Patients will be randomly assigned to receive or not receive immediate postoperative administration of celecoxib. The primary outcome is a visual analog scale (VAS) pain score the second day after surgery. Secondary outcomes include opioid consumption, VAS pain score for 7 days after surgery, range of knee motion, evaluation of sleep quality, overall evaluations by patients and physicians, rates of postoperative nausea and vomiting, and consumption of rescue analgesics. DISCUSSION: The objective of this study is to evaluate the effects of celecoxib administration immediately after surgery on pain after TKA surgery. A randomized controlled trial design will address the hypothesis that administration of oral celecoxib immediately after surgery, along with multimodal analgesia that includes peripheral nerve block and PCA, could reduce VAS pain score after TKA surgery. TRIAL REGISTRATION: UMIN-CTR 000014624 (23 July 2014). PMID- 26803748 TI - Enhanced energy transfer between Co-dopants Pyronin-Y and Thionine incorporated into modified polymethyl methacrylate with addition of ZnO nanoparticles. AB - Using a prism dye cell arrangement, the study investigated spectral energy transfer between co-dopants Pyronin-Y and Thionine incorporated into ethanol modified polymethyl methacrylate. The spectral parameters of the absorption and fluorescence spectra of the donor and acceptor dyes in the so designed solid state dye laser were calculated theoretically. Fluorescence lasing properties and slope efficiency of the solid-state dye laser were investigated both with and without addition of ZnO nanoparticles. The dye pair generally improved lasing efficiency and tunability in the range from 582 to 689 nm. PMID- 26803747 TI - The relationship between foot arch measurements and walking parameters in children. AB - BACKGROUND: Walking mechanics are influenced by body morphology. Foot arch height is one aspect of body morphology central to walking. However, generalizations about the relationship between arch height and walking are limited due to previous methodologies used for measuring the arch and the populations that have been studied. To gain the knowledge needed to support healthy gait in children and adults, we need to understand this relationship in unimpaired, typically developing children and adults using dynamic measures. The purpose of the current study was to examine the relationship between arch height and gait in a sample of healthy children and adults using dynamic measures. METHODS: Data were collected from 638 participants (n = 254 children and n = 384 adults) at the Museum of Science, Boston (MOS) and from 18 4- to 8-year-olds at the Motor Development and Motor Control Laboratories. Digital footprints were used to calculate two arch indices: the Chippaux-Smirak (CSI) and the Keimig Indices (KI). The height of the navicular bone was measured. Gait parameters were captured with a mechanized gait carpet at the MOS and three-dimensional motion analyses and in-ground force plates in the Motor Development and Motor Control Laboratories. RESULTS: Linear regression analyses on data from the MOS confirmed that as age increases, step length increases. With a linear mixed effect regression model, we found that individuals who took longer steps had higher arches as measured by the KI. However, this relationship was no longer significant when only adults were included in the model. A model restricted to children found that amongst this sample, those with higher CSI and higher KI values take longer relative step lengths. Data from the Motor Development and Motor Control Laboratories showed that both CSI and KI added to the prediction; children with lower anterior ground reaction forces had higher CSI and higher KI values. Arch height indices were correlated with navicular height. CONCLUSIONS: These results suggest that more than one measure of the arch may be needed elucidate the relationship between arch height and gait. PMID- 26803749 TI - Determination of structural elements on the folding reaction of mnemiopsin by spectroscopic techniques. AB - Mnemiopsin 1 is a member of photoprotein family, made up of 206 amino acid residues. These Ca(2+)-regulated photoproteins are responsible for light emission in a variety of marine cnidarians and ctenophores. They composed of an apoprotein, a single polypeptide chain of 25 kDa, molecular oxygen and the non covalently bound chromophore. In this study, we examined whether three mutations, namely R39K, S128G and V183T affect the thermodynamic stability as well as refolding and unfolding kinetics of mnemiopsin 1. Conformational stability measurements using fluorescence and far-UV CD spectroscopies revealed that all variants unfold in multi-step manner in which the secondary and tertiary structures are lost in different steps. However kinetic studies showed that point mutation S128G destabilizes both kinetic intermediate and native conformation; while, these structural elements are stabilized in V183T. We also found that the stability of folded and intermediate states increases in R39K. We concluded that the initial packing of helical segments within the protein structure is more facilitated when Lys with smaller side chain is present in the protein chain. PMID- 26803750 TI - Moles quantification in liquid samples by Raman spectroscopy. AB - The mole is a unit of measurement that expresses amounts of a chemical substance. Its importance lies in that the mass and the number of molecules of a substance can be determined with this value. In this work, we suggest a mathematical expression that relates the number of moles of the sample studied with the Raman signal and the experimental parameters used. In other words, with this mathematical expression it is possible to obtain quantitative information in a simple manner from Raman spectra. We have applied this method to different samples and we have observed an excellent correlation between the experimental and expected data. PMID- 26803751 TI - Hg(2+) detection using a disposable and miniaturized screen-printed electrode modified with nanocomposite carbon black and gold nanoparticles. AB - A miniaturized screen-printed electrode (SPE) modified with a carbon black-gold nanoparticle (CBNP-AuNP) nanocomposite has been developed as an electrochemical sensor for the detection of inorganic mercury ions (Hg(2+)). The working electrode surface has been modified with nanocomposite constituted of CBNPs and AuNPs by an easy drop casting procedure that makes this approach extendible to an automatable mass production of modified SPEs. Square wave anodic stripping voltammetry (SWASV) was adopted to perform Hg(2+) detection, revealing satisfactory sensitivity and detection limit, equal to 14 MUA ppb(-1) cm(-2) and 3 ppb, respectively. The applicability of the CBNP-AuNP-SPE for the determination of inorganic mercury has been assessed in river water by a simple filtration and acidification of the sample as well as in soil by means of a facile acidic extraction procedure assisted by ultrasound. PMID- 26803752 TI - Effects of Dracontomelon duperreanum defoliation extract on Microcystis aeruginosa: physiological and morphological aspects. AB - Harmful cyanobacteria bloom contributes to economic loss as well as the threat to human health. Agricultural waste products, particularly straw, have been used to control bloom while arbor plant is the potential candidate for limiting antialgal activity. This study investigated the use of Dracontomelon duperreanum defoliation extract (DDDE) to inhibit the activity of Microcystis aeruginosa. The primary goal of the research was to explore the solution to control cyanobacterial bloom. The photosynthetic activity, cell morphology, membrane integrity, and esterase activity of M. aeruginosa were determined using phytoplankton analyzer pulse amplitude modulation (Phyto-PAM) and flow cytometry before and after exposure to DDDE. The inhibitory rate of M. aeruginosa was about 99.6 % on day 15 when exposed to 2.0 g L(-1). A reduction of chlorophyll a (Chl a) activity and changes in cell membrane suggested the algistatic property of DDDE. Inhibition of photosynthetic activity was reflected by changing mean Chl-a fluorescence intensity (MFI) which was about 52.5 % on day 15 when exposed to 2.0 g L(-1) DDDE as well as relative electron transport rates (rETRs) of algal cell. These changes might contribute to the suppression of M. aeruginosa. Algal cell exposed to DDDE may lead to cell volume reduction or slow growth. This resulted in a decreased proportion of normal or swollen granular cells after DDDE treatment. PMID- 26803753 TI - Total Weight Loss as the Outcome Measure of Choice After Roux-en-Y Gastric Bypass. AB - BACKGROUND: Currently, there is no agreement on the best method to describe weight loss (WL) after bariatric surgery. The aim of this study is to evaluate short-term outcomes using percent of total body weight loss (%TWL). METHODS: A single-institution retrospective study of 2420 patients undergoing Roux-en-Y gastric bypass (RYGB) was performed. Suboptimal WL was defined as %TWL < 20 % at 12 months. RESULTS: Mean preoperative BMI was 46.8 +/- 7.8 kg/m(2). One year after surgery, patients lost an average 14.1 kg/m(2) units of body mass index (BMI), 30.0 +/- 8.5 %TWL, and 68.5 +/- 22.9 %EWL. At 6 and 12 months after RYGB, mean BMI and percent excess WL (%EWL) significantly improved for all baseline BMI groups (p < 0.01, BMI; p = 0.01, %EWL), whereas mean %TWL was not significantly different among baseline BMI groups (p = 0.9). The regression analysis between each metric outcome and preoperative BMI demonstrated that preoperative BMI did not significantly correlate with %TWL at 1 year (r = 0.04, p = 0.3). On the contrary, preoperative BMI was strongly but negatively associated with the %EWL (r = -0.52, p < 0.01) and positively associated with the BMI units lost at 1 year (r = 0.56, p < 0.01). In total, 11.3 % of subjects achieved <20 %TWL at 12 months and were considered as suboptimal WL patients. CONCLUSION: The results of our study confirm that %TWL should be the metric of choice when reporting WL because it is less influenced by preoperative BMI. Eleven percent of patients failed to achieve successful WL during the in the first year after RYGB based on our definition. PMID- 26803754 TI - The Correlation Between Obesity-Related Diseases and Non-alcoholic Fatty Liver Disease in Women in the Pre-operative Evaluation for Bariatric Surgery Assessed by Transient Hepatic Elastography. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common, severe disease in obese patients. However, NAFLD is usually underestimated by ultrasonography. Liver biopsy is not routinely done in bariatric surgery or during the follow-up. This study therefore examined the correlation between metabolic syndrome and NAFLD in morbidly obese patients based on an assessment using transient hepatic elastography (THE). MATERIAL AND METHODS: This study involved 50 female patients in the pre-operative phase for bariatric surgery. Before surgery, we collected clinical, laboratory, and anthropometric variables. THE measurements were obtained using a FibroScan(r) device (Echosens, Paris, France), and steatosis was quantified using Controlled Attenuation Parameter software (CAP). Statistical analyses were done using linear correlation and the Kruskal-Wallis test. RESULTS: The mean of THE and CAP values were 7.56 +/- 4.78 kPa and 279.94 +/- 45.69 dB/m, respectively, and there was a significant linear correlation between the two measurements (r = 0.651; p < 0.001). The numbers of metabolic syndrome parameters did not influence the THE (p = 0.436) or CAP (p = 0.422) values. HbA1c and HOMA IR showed a strong linear correlation with CAP (r = 0.643, p = 0.013 and r = 0.668, p = 0.009, respectively) and a tendency to some linear correlation with THE (r = 0.500, p = 0.05 and r = 0.500, p = 0.002, respectively). CONCLUSION: Morbidly obese women submitted to FibroScan(r) presented a high prevalence of severe steatosis and advanced fibrosis in our sample. Insulin resistance parameters were correlated with steatosis, but less with fibrosis. PMID- 26803755 TI - The system neurophysiological basis of backward inhibition. AB - Task switching is regularly required in our everyday life. To succeed in switching, it is important to inhibit the most recently performed task and instead activate the currently relevant task. The process that inhibits a recently performed task when a new task is to be performed is referred to as 'backward inhibition' (BI). While the BI effect has been subject to intense research in cognitive psychology, little is known about the neuronal mechanisms that are related to the BI effect and those that relate to differences in the magnitude of the BI effect. In the current study, we examined the system neurophysiological basis of BI processes using event-related potentials (ERPs) and sLORETA by also taking inter-individual differences in the magnitude of the BI into account. The results suggest that BI processes and inter-individual differences in them strongly depend upon attentional selection mechanisms (reflected by N1-ERP modulations in the current task/trial) mediated via networks consisting of extrastriate occipital areas, the temporo-parietal junction and the inferior frontal gyrus. Other processes and mechanisms related to conflict monitoring, response selection, or the updating, organization and implementation of a new task-set (i.e. N2 and P3 processes) were not shown to be modulated by BI processes and differences in their magnitude, as evoked with a common BI paradigm. PMID- 26803756 TI - Pneumolysin plays a key role at the initial step of establishing pneumococcal nasal colonization. AB - Nasopharyngeal colonization by Streptococcus pneumoniae is an important initial step for the subsequent development of pneumococcal infections. Pneumococci have many virulence factors that play a role in colonization. Pneumolysin (PLY), a pivotal pneumococcal virulence factor for invasive disease, causes severe tissue damage and inflammation with disruption of epithelial tight junctions. In this study, we evaluated the role of PLY in nasal colonization of S. pneumoniae using a mouse colonization model. A reduction of numbers of PLY-deficient pneumococci recovered from nasal tissue, as well as nasal wash, was observed at days 1 and 2 post-intranasal challenges, but not later. The findings strongly support an important role for PLY in the initial establishment nasal colonization. PLY dependent invasion of local nasal mucosa may be required to establish nasal colonization with S. pneumoniae. The data help provide a rationale to explain why an organism that exists as an asymptomatic colonizer has evolved virulence factors that enable it to occasionally invade and kill its hosts. Thus, the same pneumococcal virulence factor, PLY that can contribute to killing the host, may also play a role early in the establishment of nasopharynx carriage. PMID- 26803757 TI - The ecology of Zymomonas: a review. AB - Zymomonas mobilis is a Gram-negative bacterium studied primarily as a spoilage organism and ethanol producer. As with many bacteria, much remains to be learned about its ecology. It can serve as a model organism for examining microbial interactions, as well as interactions between plants and bacteria. Better understanding of its ecology can help with biotechnological applications, such as process improvement, new uses of the bacterium, and the search for new strains. PMID- 26803758 TI - Asterixis in the leg induced by anterior cerebral artery infarction. AB - Asterixis commonly occurs in a patient with metabolic encephalopathy, whereas focal brain lesions such as thalamus, cerebellum, or frontal area also cause focal or unilateral asterixis in the arms. We report a novel case of asterixis in the leg after unilateral anterior cerebral artery territory infarction. A 76-year old man was admitted with sudden-onset mild right leg weakness and postural instability due to knee buckling. He was diagnosed with ischemic stroke in the left prefrontal area and cingulated gyrus by brain magnetic imaging. Needle electromyography of the right vastus lateralis muscle while standing showed intermittent periods of EMG silence, consistent with asterixis. There were no abnormal involuntary movements in the upper extremities. This case suggests that gait disturbance or postural instability after structural lesions in the prefrontal area may be directly related to asterixis in the leg, not in the arm associated with postural failure. PMID- 26803761 TI - Retraction Note to: A study on cognitive impairment and gray matter volume abnormalities in silent cerebral infarction patients. PMID- 26803759 TI - Recommendations for Primary Care Provided by Psychiatrists. AB - Recent studies have shown that people with severe mental illness have a dramatically lower life expectancy than the general population. Psychiatrists have not traditionally been very attentive to or involved with physical health issues and there has been growing emphasis on integrated care for physical and mental health and access to primary care for all members of the population. This paper examines the role of psychiatrists in the provision of primary care to the patients they treat. Some recommendations are offered for their involvement in the provision of primary care at three levels of complexity: Level 1--Universal Basic Psychiatric Primary Care; Level 2--Enhanced Psychiatric Primary Care; and Level 3--Fully Integrated Primary Care and Psychiatric Management. Some of the obstacles to the provision of primary care by psychiatrists are considered along with some suggestions for overcoming them. PMID- 26803763 TI - Acidic Potassium Permanganate Chemiluminescence for the Determination of Antioxidant Potential in Three Cultivars of Ocimum basilicum. AB - Ocimum basilicum, a member of the family Lamiaceae, is a rich source of polyphenolics that have antioxidant properties. The present study describes the development and application of an online HPLC-coupled acidic potassium permanganate chemiluminescence assay for the qualitative and quantitative assessment of antioxidants in three cultivars of O. basilicum grown under greenhouse conditions. The chemiluminescence based assay was found to be a sensitive and efficient method for assessment of total and individual compound antioxidant potential. Leaves, flowers and roots were found to be rich reserves of the antioxidant compounds which showed intense chemiluminescence signals. The polyphenolics such as rosmarinic, chicoric, caffeic, p-coumaric, m-coumaric and ferulic acids showed antioxidant activity. Further, rosmarinic acid was found to be the major antioxidant component in water-ethanol extracts. The highest levels of rosmarinic acid was found in the leaves and roots of cultivars "holy green" (14.37; 11.52 mM/100 g DW respectively) followed by "red rubin" (10.02; 10.75 mM/100 g DW respectively) and "subja" (6.59; 4.97 mM/100 g DW respectively). The sensitivity, efficiency and ease of use of the chemiluminescence based assay should now be considered for its use as a primary method for the identification and quantification of antioxidants in plant extracts. PMID- 26803765 TI - Altererythrobacter terrae sp. nov., isolated from mountain soil. AB - A Gram-negative, non-motile, non-spore-forming, ovoid-shaped bacterium designated as SWU3(T) was isolated from mountain soil collected at Seoul Women's University, South Korea. Based on 16S rRNA sequence analysis, strain SWU3(T) was found to belong to the genus Altererythrobacter. It shares high sequence similarities with A. dongtanensis JM27(T) (96.6 %), A. epoxidivorans JCS350(T) (96.6 %), and A. troitsensis KMM 6042(T) (96.5 %). Growth was observed between 15 and 37 degrees C (optimum, 30 degrees C) with pH of 6-9 (optimum, pH 7.0). It could tolerate 0 2 % (w/v) NaCl. Its predominant quinone was found to be ubiquinone (Q-10). Its major cellular fatty acids were determined to be C17:1 omega6c, C18:1 omega7c, and summed featured 3 (C16:1 omega7c/C16:1 omega6c), all of which are similar characteristics to those of species within the genus Altererythrobacter. Its G + C molar content was found to be 58.4 mol%. Phylogenetic evidence, together with phenotypic characteristics showed that strain SWU3(T) represents a new species of the genus Altererythrobacter. The name Altererythrobacter terrae sp. nov. is proposed and the type strain is SWU3(T) (=KEMB 9004-128(T) = JCM 19177(T)). PMID- 26803764 TI - Rapid versus non-rapid cycling bipolar II depression: response to venlafaxine and lithium and hypomanic risk. AB - OBJECTIVE: To examine the safety and effectiveness of antidepressant versus mood stabilizer monotherapy in rapid versus non-rapid cycling bipolar II disorder. METHOD: Subjects >=18 years old with bipolar II depression (n = 129) were randomized to double-blind venlafaxine or lithium carbonate monotherapy for 12 weeks. Responders (n = 59) received continuation monotherapy for six additional months. RESULTS: Rapid cycling did not affect frequency of response or change over time in depressive symptoms. Rapid cycling status did not affect frequency of depressive relapse or sustained treatment response. Rapid cyclers were more likely to experience hypomanic symptoms (P = 0.005) during continuation monotherapy; however, rates were similar in venlafaxine (17.6%) and lithium (42.9%) (P = 0.31). CONCLUSION: Rapid cycling status may not be associated with an increased risk of diminished response or greater depressive relapse during venlafaxine, relative to lithium monotherapy, in bipolar II subjects. Additional randomized studies are needed to confirm these findings. PMID- 26803767 TI - Clinical staging of ketamine-associated urinary dysfunction: a strategy for assessment and treatment. AB - PURPOSE: To describe a clinical staging method linked to stepwise treatment indications for ketamine-associated urinary dysfunction (KAUD) based on review of our experience in management of KAUD patients and analysis of their clinical features. METHODS: The eighty-one KAUD patients hospitalized from January 2008 to June 2014 were studied retrospectively. According to ketamine history, renal and liver function, bladder change and up urinary tract involvement, patients were categorized into a described model of three stages. Discriminant analysis was applied to validate the model. The void volume, micturition interval, nocturnal void frequency and pelvic pain and urgency/frequency (PUF) questionnaire score were, respectively, compared after treatments. RESULTS: There were, respectively, 24, 47 and 10 patients in three stages. The duration of abuse varied (p = 0.047) correlated with clinical stages (p = 0.015, r = 0.268). The severity of LUTS was not significant. The creatinine, estimated glomerular filtration rate and liver function were worse in higher stages (p < 0.01), and the incidence of ureteral change and hydronephrosis was greater (p < 0.001). Based on the model, cross validation confirmed 83.1 % cases were classified correctly. Twenty-four patients in stage I were treated with behavioral modification and pharmacotherapy, thirty five patients in stage II with hydrodistention and six patients in stage III with surgical intervention due to rapid progression after conservative therapy. All patients in three stages demonstrated improvements in void volume, micturition interval, nocturnal void frequency and PUF score (all p < 0.05) after treatment. CONCLUSION: Clinical staging could serve for assessment of progression, and the staging-based treatment is effective. This model still awaits further validation. PMID- 26803768 TI - The Fokker-Planck law of diffusion and pattern formation in heterogeneous environments. AB - We analyze the influence of spatially inhomogeneous diffusion on several common ecological problems. Diffusion is modeled with Fick's law and the Fokker-Planck law of diffusion. We discuss the differences between the two formalisms and when to use either the one or the other. In doing so, we start with a pure diffusion equation, then turn to a reaction-diffusion system with one logistically growing component which invades the spatial domain. We also look at systems of two reacting components, namely a trimolecular oscillating chemical model system and an excitable predator-prey model. Contrary to Fickian diffusion, spatial inhomogeneities promote spatial and spatiotemporal pattern formation in case of Fokker-Planck diffusion. PMID- 26803769 TI - Comparison of Feature Selection Techniques in Machine Learning for Anatomical Brain MRI in Dementia. AB - We present a comparative split-half resampling analysis of various data driven feature selection and classification methods for the whole brain voxel-based classification analysis of anatomical magnetic resonance images. We compared support vector machines (SVMs), with or without filter based feature selection, several embedded feature selection methods and stability selection. While comparisons of the accuracy of various classification methods have been reported previously, the variability of the out-of-training sample classification accuracy and the set of selected features due to independent training and test sets have not been previously addressed in a brain imaging context. We studied two classification problems: 1) Alzheimer's disease (AD) vs. normal control (NC) and 2) mild cognitive impairment (MCI) vs. NC classification. In AD vs. NC classification, the variability in the test accuracy due to the subject sample did not vary between different methods and exceeded the variability due to different classifiers. In MCI vs. NC classification, particularly with a large training set, embedded feature selection methods outperformed SVM-based ones with the difference in the test accuracy exceeding the test accuracy variability due to the subject sample. The filter and embedded methods produced divergent feature patterns for MCI vs. NC classification that suggests the utility of the embedded feature selection for this problem when linked with the good generalization performance. The stability of the feature sets was strongly correlated with the number of features selected, weakly correlated with the stability of classification accuracy, and uncorrelated with the average classification accuracy. PMID- 26803770 TI - Human iPS cell model of type 3 long QT syndrome recapitulates drug-based phenotype correction. AB - Long QT syndrome is a potentially life-threatening disease characterized by delayed repolarization of cardiomyocytes, QT interval prolongation in the electrocardiogram, and a high risk for sudden cardiac death caused by ventricular arrhythmia. The genetic type 3 of this syndrome (LQT3) is caused by gain-of function mutations in the SCN5A cardiac sodium channel gene which mediates the fast Nav1.5 current during action potential initiation. Here, we report the analysis of LQT3 human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). These were generated from a patient with a heterozygous p.R1644H mutation in SCN5A known to interfere with fast channel inactivation. LQT3 hiPSC CMs recapitulated pathognomonic electrophysiological features of the disease, such as an accelerated recovery from inactivation of sodium currents as well as action potential prolongation, especially at low stimulation rates. In addition, unlike previously described LQT3 hiPSC models, we observed a high incidence of early after depolarizations (EADs) which is a trigger mechanism for arrhythmia in LQT3. Administration of specific sodium channel inhibitors was found to shorten action and field potential durations specifically in LQT3 hiPSC-CMs and antagonized EADs in a dose-dependent manner. These findings were in full agreement with the pharmacological response profile of the underlying patient and of other patients from the same family. Thus, our data demonstrate the utility of patient-specific LQT3 hiPSCs for assessing pharmacological responses to putative drugs and for improving treatment efficacies. PMID- 26803772 TI - Voluntary Cough Airflow Differentiates Safe Versus Unsafe Swallowing in Amyotrophic Lateral Sclerosis. AB - Dysphagia and aspiration are prevalent in amyotrophic lateral sclerosis (ALS) and contribute to malnutrition, aspiration pneumonia, and death. Early detection of at risk individuals is critical to ensure maintenance of safe oral intake and optimal pulmonary function. We therefore aimed to determine the discriminant ability of voluntary cough airflow measures in detecting penetration/aspiration status in ALS patients. Seventy individuals with ALS (El-Escorial criteria) completed voluntary cough spirometry testing and underwent a standardized videofluoroscopic swallowing evaluation (VFSE). A rater blinded to aspiration status derived six objective measures of voluntary cough airflow and evaluated airway safety using the penetration-aspiration scale (PAS). A between groups ANOVA (safe vs. unsafe swallowers) was conducted and sensitivity, specificity, area under the curve (AUC) and likelihood ratios were calculated. VFSE analysis revealed 24 penetrator/aspirators (PAS >=3) and 46 non-penetrator/aspirators (PAS <=2). Cough volume acceleration (CVA), peak expiratory flow rise time (PEFRT), and peak expiratory flow rate (PEFR) were significantly different between airway safety groups (p < 0.05) and demonstrated significant discriminant ability to detect the presence of penetration/aspiration with AUC values of: 0.85, 0.81, and 0.78, respectively. CVA <45.28 L/s/s, PEFR <3.97 L/s, and PEFRT >76 ms had sensitivities of 91.3, 82.6, and 73.9 %, respectively, and specificities of 82.2, 73.9, and 78.3 % for identifying ALS penetrator/aspirators. Voluntary cough airflow measures identified ALS patients at risk for penetration/aspiration and may be a valuable screening tool with high clinical utility. PMID- 26803771 TI - GLP-1 Agonists and Blood Pressure: A Review of the Evidence. AB - Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease. The presence of concomitant hypertension in diabetics is a major driver of excess cardiovascular risk. Glucagon-like peptide-1 receptor agonists (GLP-1a) act on numerous pathways that intersect glycemic, weight, and blood pressure (BP) control. BP-lowering effects have been observed in mouse models of hypertension with a variety of GLP-1a. Acute administration of GLP-1a in humans has been shown to no effects and sometimes increased BP in humans. Chronic administration of GLP 1a, however, reduces clinic systolic BP (~2 mmHg) at least when evaluated as a secondary end point in glycemia-lowering studies while simultaneously increasing heart rate. BP lowering has not been consistently observed in two recent double blind controlled clinical trials evaluating ambulatory BP as the primary end point. While a number of mechanisms including vascular, myocardial, renal, and central nervous system pathways have been suggested in animal studies, these mechanistic pathways have not been sufficiently detailed in humans and it is unclear if the same pathways are operational. Further studies need to be conducted to unravel the full spectrum of effects of this drug class. An understanding of their effects on BP may help provide an explanation for the ability of GLP-1a to influence cardiovascular (CV) events in ongoing event-driven CV trials. PMID- 26803773 TI - Validation of Clinical Observations of Mastication in Persons with ALS. AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease that can result in difficulties with mastication leading to malnutrition, choking or aspiration, and reduced quality of life. When evaluating mastication, clinicians primarily observe spatial and temporal aspects of jaw motion. The reliability and validity of clinical observations for detecting jaw movement abnormalities is unknown. The purpose of this study is to determine the reliability and validity of clinician-based ratings of chewing performance in neuro-typical controls and persons with varying degrees of chewing impairments due to ALS. Adults chewed a solid food consistency while full-face video were recorded along with jaw kinematic data using a 3D optical motion capture system. Five experienced speech language pathologists watched the videos and rated the spatial and temporal aspects of chewing performance. The jaw kinematic data served as the gold standard for validating the clinicians' ratings. Results showed that the clinician-based rating of temporal aspects of chewing performance had strong inter-rater reliability and correlated well with comparable kinematic measures. In contrast, the reliability of rating the spatial and spatiotemporal aspects of chewing (i.e., range of motion of the jaw, consistency of the chewing pattern) was mixed. Specifically, ratings of range of motion were at best only moderately reliable. Ratings of chewing movement consistency were reliable but only weakly correlated with comparable measures of jaw kinematics. These findings suggest that clinician ratings of temporal aspects of chewing are appropriate for clinical use, whereas ratings of the spatial and spatiotemporal aspects of chewing may not be reliable or valid. PMID- 26803774 TI - Observers' Agreement on Measurements in Fiberoptic Endoscopic Evaluation of Swallowing. AB - This study analyzed the effect that dysphagia etiology, different observers, and bolus consistency might have on the level of agreement for measurements in FEES images reached by independent versus consensus panel rating. Sixty patients were included and divided into two groups according to dysphagia etiology: neurological or head and neck oncological. All patients underwent standardized FEES examination using thin and thick liquid consistencies. Two observers scored the same exams, first independently and then in a consensus panel. Four ordinal FEES variables were analyzed. Statistical analysis was performed using a linear weighted kappa coefficient and Bayesian multilevel model. Intra- and interobserver agreement on FEES measurements ranged from 0.76 to 0.93 and from 0.61 to 0.88, respectively. Dysphagia etiology did not influence observers' agreement level. However, bolus consistency resulted in decreased interobserver agreement for all measured FEES variables during thin liquid swallows. When rating on the consensus panel, the observers deviated considerably from the scores they had previously given on the independent rating task. Observer agreement on measurements in FEES exams was influenced by bolus consistency, not by dysphagia etiology. Therefore, observer agreement on FEES measurements should be analyzed by taking bolus consistency into account, as it might affect the interpretation of the outcome. Identifying factors that might influence agreement levels could lead to better understanding of the rating process and assist in developing a more precise measurement scale that would ensure higher levels of observer agreement for measurements in FEES exams. PMID- 26803775 TI - Validation of the Spanish Version of the Eating Assessment Tool-10 (EAT-10spa) in Colombia. A Blinded Prospective Cohort Study. AB - Dysphagia might affect 12 % of the general population, and its complications include pneumonia, malnutrition, social isolation, and death. No validated Spanish symptom survey exists to quantify dysphagia symptoms among Latin Americans. Therefore, we performed a prospective cohort study in a tertiary care university hospital to validate the Spanish version of the 10-Item Eating Assessment-Tool (EAT-10spa) for use in Colombia. After an interdisciplinary committee of five bilingual specialists evaluated the EAT-10spa (translated and validated in Spain) and deemed it appropriate for the Colombian culture, its feasibility, reliability, validity, sensitivity to change, and diagnostic capacity were evaluated. As a reference standard, we used the flexible endoscopic evaluation of swallowing with sensory testing and a standardized clinical evaluation. All assessments were blinded. In total, 133 subjects were included (52 % women, mean age 55 years) and completed the EAT-10spa (median completion time: 2 min [IQR 1-3 min]), 39 % of whom had an elementary-level education. Cronbach's alpha coefficient: 0.91; test-retest intra-class correlation coefficient: 0.94. The Spearman's correlation coefficient of the EAT-10spa with the 8-point penetration-aspiration scale was 0.54 (P < 0.001). The area under the receiver-operating-characteristic-curve (AUC-ROC) for dysphagia and aspiration were 0.79 (P < 0.001) and 0.81 (P < 0.001), respectively. The best cut-off points for dysphagia and aspiration were EAT-10spa >=2 (sensitivity 93.6 %, specificity 36.4 %) and EAT-10spa >=4 (sensitivity 94.3 %, specificity 49.5 %), respectively. A reduction in the EAT-10 >=3 was the best cut-off point for a clinically significant improvement (AUC-ROC 0.83; P < 0.0001). The EAT-10spa showed excellent psychometric properties and discriminatory capacity for use in Colombia. PMID- 26803776 TI - Simulation-Based Dysphagia Training: Teaching Interprofessional Clinical Reasoning in a Hospital Environment. AB - This study evaluated hospital readiness and interprofessional clinical reasoning in speech-language pathology and dietetics students following a simulation-based teaching package. Thirty-one students participated in two half-day simulation workshops. The training included orientation to the hospital setting, part-task skill learning and immersive simulated cases. Students completed workshop evaluation forms. They filled in a 10-question survey regarding confidence, knowledge and preparedness for working in a hospital environment before and immediately after the workshops. Students completed written 15-min clinical vignettes at 1 month prior to training, immediately prior to training and immediately after training. A marking rubric was devised to evaluate the responses to the clinical vignettes within a framework of interprofessional education. The simulation workshops were well received by all students. There was a significant increase in students' self-ratings of confidence, preparedness and knowledge following the study day (p < .001). There was a significant increase in student overall scores in clinical vignettes after training with the greatest increase in clinical reasoning (p < .001). Interprofessional simulation-based training has benefits in developing hospital readiness and clinical reasoning in allied health students. PMID- 26803777 TI - The natural history of depression and trajectories of symptoms long term after stroke: The prospective south London stroke register. AB - BACKGROUND: The natural history of depression in stroke patients is complex and the mechanism of change in symptoms over time is not fully understood. We hypothesise that there are different trajectories of symptoms after stroke. METHODS: The primary analysis comprised 761 patients who completed 5 years follow up, obtained from the prospective South London Stroke Register (1998-2013). The Hospital Anxiety and Depression scale (HADs) was used to screen patients for depression symptoms at 3 months after stroke, then annually. Trajectories of depression symptoms were detected using group based trajectory modelling (GBTM). RESULTS: Four patterns of symptoms (Groups I-IV) were identified: 6.31% of patients had severe symptoms, improved slightly in early years then worsen (predicted mean HADs score, 15.74 (se=1.06)); 28.65% had moderate symptoms, a tendency to get worse over time, predicted mean score 7.36 (se=0.35); 49.54% had mild symptoms and a tendency of getting worse, predicted mean 3.89 (se=0.30), and 15.51% of the cohort, had no symptoms and remained so over time. The lowest rate of Selective serotonin reuptake inhibitors (SSRI) use, over 5 years after stroke was 1.1% for group (I) and highest was 35% for group (IV). Sensitivity analyses were used to assess the robustness of the findings using several inclusion criteria and findings agreed with the primary results. LIMITATIONS: There is loss to follow up of around 20%. CONCLUSIONS: The study identified 4 trajectories of depression symptoms, providing useful information for the long term management of stroke patients and for the implementation of cost effective personalized interventions. PMID- 26803778 TI - Dysfunctional decision-making related to white matter alterations in bipolar I disorder. AB - OBJECTIVE: This study investigated how frontal white matter (WM) alterations in patients with bipolar I disorder (BD-I) are linked to motivational dysregulation, often reported in the form of risk-taking and impulsivity, and whether structure function relations in patients might differ from healthy subjects (HC). METHOD: We acquired diffusion data from 24 euthymic BD-I patients and 24 controls, to evaluate WM integrity of selected frontal tracts. Risk-taking was assessed by the Cambridge Gambling Task and impulsivity by self-report with the Barratt Impulsiveness Scale. RESULTS: BD-I patients displayed significantly lower integrity in the right cingulum compared to HC. They also showed more risk-taking behavior and reported increased trait-impulsivity. Risk-taking was negatively associated with WM integrity in the right cingulum. Impulsivity was not related to WM integrity in investigated tracts. Together with age and sex, FA in the cingulum explained 25% of variance in risk-taking scores in all study participants. The left inferior fronto-occipital fasciculus (IFOF) was specifically predictive of risk-taking behavior in BD-I patients, but not in HC. LIMITATIONS: The employed parameters did not allow us to specify the exact origin of WM changes, nor did the method allow the analysis of specific brain subregions. Also, sample size was moderate and the sample included patients with lifetime alcohol dependence/abuse, hence effects found need replication and have to be interpreted with caution. CONCLUSION: Our results further strengthen recent models linking structural changes in frontal networks to behavioral markers of BD I. They extend recent findings by showing that risk-taking is also linked to the cingulum in BD-I and HC, while other prefrontal tracts (IFOF) are specifically implicated in risk-taking behavior in BD-I patients. Meanwhile, self-reported impulsivity was not associated with WM integrity of the tracts investigated in our study. PMID- 26803779 TI - The effectiveness of platform screen doors for the prevention of subway suicides in South Korea. AB - BACKGROUND: Subway suicide can significantly impact the general public. Platform Screen Doors (PSDs) are considered to be an effective strategy to prevent suicides at subway stations, but the evidence on their effectiveness is limited. METHODS: We assessed the effectiveness of installing half- and full-height platform screen doors in reducing subway suicides using Poisson regression analysis. Ten-year monthly panel data for 121 subway stations between 2003 and 2012 in the Seoul metropolitan area were used for the analysis. RESULTS: We found that installing PSDs decreases fatal suicide cases by 89% (95% CI: 57-97%). We also found that the installation of full-height PSDs resulted in the elimination of subway suicides by completely blocking access to the track area; however, half height PSDs, which do not extend to the ceiling of the platform, were not as effective as full-height ones. LIMITATION: Our findings were based on the data from a single subway operator for a limited period of time. Accordingly, we did not consider the possibility that some passengers choose to die at a station run by other operators. Our study did not examine the potential substitution effects of other suicide methods. CONCLUSION: Installing physical barriers at subway stations can be an effective strategy to reduce the number of subway suicides; however, half-height PSDs are not as effective as full-height ones, even when they are as high as the height of an adult. Thus, these barriers should be made high enough so that nobody can climb over them. PMID- 26803780 TI - A meta-analysis of temperament and character dimensions in patients with mood disorders: Comparison to healthy controls and unaffected siblings. AB - BACKGROUND: Cloninger's psychobiological model of personality has been extensively applied to subjects affected by mood disorders (MOOD). However, most studies are widely heterogeneous in terms of sample size, methods of assessment, and selection of participants. METHODS: We conducted a systematic review of literature and a random effects meta-analysis of studies comparing at least two of the following groups: (a) adults with a primary MOOD diagnosis (Bipolar Disorder (BP) or major depressive disorder (MDD)), (b) their unaffected siblings (SIB) or (c) healthy subjects (HS), and reporting quantitative results from the Tridimensional Personality Questionnaire (TPQ) or the Temperament and Character Inventory (TCI). Subgroup, sensitivity and meta-regression analyses were also conducted. RESULTS: High Harm Avoidance and low Self-Directedness were consistently associated with MOOD and SIB samples. BP was characterized by higher scores in Novelty Seeking and Self-Transcendence than HS, SIB and MDD. Age seemed to have a negative effect on Novelty Seeking and a positive effect on Harm Avoidance, Cooperativeness and Self-Transcendence. An euthymic mood state was associated with reduced Harm Avoidance, but increased Reward Dependence, Self Directedness and Cooperativeness. LIMITATIONS: The quality of the included studies varied and was relatively low. Moreover, publication bias and heterogeneity in the distribution of effect sizes may also have limited our results. CONCLUSION: High Harm Avoidance and Low Self-Directedness may be trait markers for MOOD in general, while high Novelty Seeking and high Self Transcendence may be specific to BP. Future studies are needed to disentangle the state-trait effect of each personality dimension. PMID- 26803781 TI - Emotional and physiological reactivity in Complicated Grief. AB - BACKGROUND: Grief is a psychobiological response to the loss of a loved one. Some grief theorists suggest that this predictable response may arise from withdrawal of psychobiological regulation previously provided by the deceased (e.g. assistance with emotion regulation). Accordingly, recovery from loss may require bereaved individuals to re-establish self-regulatory control to avoid developing Complicated Grief (CG). This model implies that adults with CG may exhibit aberrant emotional responding to environmental stimuli. The present study was designed to test this hypothesis. METHODS: We recruited a sample of 23 bereaved adults with CG and 26 healthy bereaved adults to complete an emotional reactivity paradigm. Participants watched a series of emotional film clips and provided measures of their self-reported emotional response. We also assessed their heart rate, respiratory sinus arrhythmia (RSA), and skin conductance level in response to these clips. RESULTS: Though emotional and physiological differences between the groups were rare, the CG group exhibited attenuated RSA reactivity to some emotional film clips, suggesting blunted parasympathetic nervous system reactivity in those with the disorder. LIMITATIONS: Limitations include the modest sample size and unequal group sizes. CONCLUSIONS: Individuals with CG do not exhibit pervasive differences in emotional and physiological reactivity compared to healthy bereaved individuals. However, we did observe evidence of blunted parasympathetic nervous system reactivity in individuals with CG, which may mediate emotional inflexibility among those who develop the disorder. PMID- 26803782 TI - Associations between intimate partner violence (IPV) during pregnancy, mother-to infant bonding failure, and postnatal depressive symptoms. AB - This study examined the associations between intimate partner violence (IPV) during pregnancy, mother-to-infant bonding failure, and postnatal depressive symptoms at 1 month postnatal. This study also examined if these relationships would be mediated by antenatal depressive symptoms. This study was a prospective cohort study that investigated effects between the third trimester of pregnancy and 1 month after childbirth. The Japanese version of the Index of Spouse Abuse (ISA), the Japanese version of the Mother-Infant Bonding Scale (MIBS), and the Japanese version of the Hospital Anxiety and Depression Scale (HADS) were used to measure IPV during pregnancy, bonding failure with infants, and depressive symptoms during pregnancy and the postnatal period respectively. Structural equation modeling (SEM) was used to find the associations between those four variables. The final path model of the SEM showed good fit with the data. IPV during pregnancy was associated with mother-to-infant bonding failure at 1 month postnatal, whereas IPV during pregnancy was not significantly associated with postnatal depressive symptoms at 1 month postnatal. In addition, this study demonstrated that the associations between IPV during pregnancy, mother-to-infant bonding failure, and postnatal depressive symptoms at 1 month postnatal were mediated by antenatal depressive symptoms. The results of this study indicated the need for interventions for IPV and psychological health care for abused pregnant women to prevent antenatal depressive symptoms in prenatal health settings. Those interventions by perinatal health professionals would help to prevent bonding failure with infants and postnatal depressive symptoms after childbirth. PMID- 26803784 TI - Pre-pubescent posterior cruciate ligament (PCL) reconstruction using maternal allograft. AB - PURPOSE: Posterior cruciate ligament (PCL) reconstruction is a challenge in the pre-pubescent and paediatric age group. It requires great skill in tunnel and graft placement and fixation through open physes. Another major concern is the source of graft, as the thickness of harvested hamstring graft is unpredictable in children and the bone patella tendon bone graft cannot be used due to un ossified patella and tibial tuberosity. Quadriceps being an important agonist of PCL, we decided not to use it as a graft source. METHODS: PCL reconstruction was done in three pre-pubescent children aged 3.5, 7 and 10 years using maternal allograft with follow-up of 7, 9 and 7 years (the 10-year-old boy was lost to follow-up after 2013), respectively. RESULTS: All the patients showed excellent results with the median IKDC Pedi improving to 90 (85-92) at latest follow-up as against 29.9 (25-35) pre-operatively. The median Lysholm score improved from 45 (42-47) to 100 (95-100). The posterior drawer test showed no PCL laxity during the latest follow-up. The grafts were accepted well by all three with no evidence of graft rejection or tissue reaction. CONCLUSION: Living donor allografts may be a good option for paediatric ligament reconstruction. This, however, must be supported with more evidence from a larger study group and a longer follow-up until the closure of physes. LEVEL OF EVIDENCE: IV. PMID- 26803783 TI - Rehabilitation after surgical treatment of peroneal tendon tears and ruptures. AB - PURPOSE: The purpose of this study was to provide an overview of the available evidence on rehabilitation programmes after operatively treated patients with peroneal tendon tearsand ruptures. METHODS: A systematic review was performed, and PubMed and EMBASE were searched for relevant studies. Information regarding the rehabilitation programme after surgical management of peroneal tendon tears and ruptures was extracted from all included studies. RESULTS: In total, 49 studies were included. No studies were found with the primary purpose to report on rehabilitation of surgically treated peroneal tendon tears or ruptures. The median duration of the total immobilization period after primary repair was 6.0 weeks (range 0-12), 7.0 weeks (range 3.0-13) after tenodesis, 6.3 weeks (range 3.0-13) after grafting, and 8.0 weeks (range 6.0-11) after end-to-end suturing. Forty one percent of the studies that reported on the start of range of motion exercises initiated range of motion within 4 weeks after surgery. No difference was found in duration of immobilization or start of range of motion between different types of surgical treatment options. CONCLUSION: Appropriate directed rehabilitation appears to be an important factor in the clinical success of surgically treated peroneal tendon tears and ruptures. There seems to be a trend towards shorter immobilization time and early range of motion, although there is no consensus in the literature on best practice recommendations for optimizing rehabilitation after surgical repair of peroneal tendon tears or ruptures. It is important to adjust the rehabilitation protocol to every specific patient for an optimal rehabilitation. LEVEL OF EVIDENCE: Systematic Review, Level IV. PMID- 26803785 TI - Biological variables and health status affecting inorganic element concentrations in harbour porpoises (Phocoena phocoena) from Portugal (western Iberian Peninsula). AB - The coastal preferences of harbour porpoise (Phocoena phocoena) intensify their exposure to human activities. The harbour porpoise Iberian population is presently very small and information about the threats it endures is vital for the conservation efforts that are being implemented to avoid local extinction. The present study explored the possible relation between the accumulation of trace elements by porpoises and their sex, body length, nutritional state, presence of parasites and gross pathologies. The concentrations of arsenic (As), cadmium (Cd), copper (Cu), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), zinc (Zn) and selenium (Se) were evaluated in 42 porpoises stranded in Portugal between 2005 and 2013. Considering European waters, porpoises stranded in Portugal present the highest Hg concentrations and the lowest Cd concentrations, which may reflect dietary preferences and the geographic availability of these pollutants. While no effect of sex on trace element concentrations was detected, there was a positive relationship between porpoise body length and the concentration of Cd, Hg and Pb. Animals in worse nutritional condition showed higher levels of Zn. Harbour porpoises with high parasite burdens showed lower levels of Zn and As in all analysed tissues and also lower levels of renal Ni, while those showing gross pathologies presented higher Zn and Hg levels. This is the first data on the relationship between trace elements and health-related variables in porpoises from southern European Atlantic waters, providing valuable baseline information about the contamination status of this vulnerable population. PMID- 26803786 TI - Shared effects of organic microcontaminants and environmental stressors on biofilms and invertebrates in impaired rivers. AB - Land use type, physical and chemical stressors, and organic microcontaminants were investigated for their effects on the biological communities (biofilms and invertebrates) in several Mediterranean rivers. The diversity of invertebrates, and the scores of the first principal component of a PCA performed with the diatom communities were the best descriptors of the distribution patterns of the biological communities against the river stressors. These two metrics decreased according to the progressive site impairment (associated to higher area of agricultural and urban-industrial, high water conductivity, higher dissolved organic carbon and dissolved inorganic nitrogen concentrations, and higher concentration of organic microcontaminants, particularly pharmaceutical and industrial compounds). The variance partition analyses (RDAs) attributed the major share (10%) of the biological communities' response to the environmental stressors (nutrients, altered discharge, dissolved organic matter), followed by the land use occupation (6%) and of the organic microcontaminants (2%). However, the variance shared by the three groups of descriptors was very high (41%), indicating that their simultaneous occurrence determined most of the variation in the biological communities. PMID- 26803787 TI - Using devitalized moss for active biomonitoring of water pollution. AB - This paper presents the results of an experiment carried out for the first time in situ to select a treatment to devitalize mosses for use in active biomonitoring of water pollution. Three devitalizing treatments for the aquatic moss Fontinalis antipyretica were tested (i.e. oven-drying at 100 degrees C, oven-drying with a 50-80-100 degrees C temperature ramp, and boiling in water), and the effects of these on loss of material during exposure of the transplants and on the accumulation of different heavy metals and metalloids were determined. The suitability of using devitalized samples of the terrestrial moss Sphagnum denticulatum to biomonitor aquatic environments was also tested. The structure of mosses was altered in different ways by the devitalizing treatments. Devitalization by boiling water led to significantly less loss of material (p < 0.01) than the oven-drying treatments. However, devitalization by oven-drying with a temperature ramp yielded more stable results in relation to both loss of material and accumulation of elements. With the aim of standardizing the moss bag technique, the use of F. antipyretica devitalized by oven-drying with a temperature ramp is recommended, rather than other devitalization treatments or use of S. denticulatum. PMID- 26803788 TI - Suspension stability and aggregation of multi-walled carbon nanotubes as affected by dissolved organic matters extracted from agricultural wastes. AB - Dissolved organic matters (DOMs) extracted from wheat straw (SDOM) and cow manure (MDOM) were used to investigate their effects on the suspension stability and aggregation of multi-walled carbon nanotubes (MWCNTs). Two types of DOM can effectively disperse and stabilize the MWCNTs. At initial MWCNT concentration of 500 mg/L, suspended MWCNT concentration ranged from 8.0 to 17.9 mg/L as DOM were varied from 50 to 200 mg/L dissolved organic carbon (DOC). The critical coagulation concentration (CCC) values were estimated to be 41.4 mM NaCl and 5.3 mM CaCl2 in the absence of DOM. The presence of SDOM and MDOM significantly retarded the aggregation rate of MWCNTs. The CCC values increased to 120 mM NaCl and 14.8 mM CaCl2 at SDOM concentration of 20 mg/L DOC. Due to its higher aromaticity and molecular weight, MDOM showed higher ability to stabilize MWCNTs, with CCC values of 201 mM and 15.8 mM at 20 mg/L DOC. These findings revealed that DOMs originated from agricultural wastes will have great impact on the dispersion and stabilization of MWCNTs, thus their fate in the aquatic environment. PMID- 26803789 TI - In situ investigation into surfactant effects on the clearance of polycyclic aromatic hydrocarbons adsorbed onto soybean leaf surfaces. AB - The partitioning of polycyclic aromatic hydrocarbons (PAHs) in agricultural crop leaves, contributes to the exposure of organisms to these chemicals through the dietary pathway. To precisely predict the fate of PAHs and crop safety, the clearance of three-ringed phenanthrene (Phe) and four-ringed pyrene (Pyr) adsorbed individually onto living soybean leaf surfaces, as well as the effects of two surfactants, namely, an ionic surfactant (sodium dodecylbenzene sulfonate, SDBS) and a non-ionic surfactant (polyoxyethyleneglycol dodecyl ether, Brij35), were investigated in situ using the laser-induced nanosecond time-resolved fluorescence (LITRF) method. The effects varied significantly with surfactant types primarily in terms of the elimination rates and the final residues of PAH chemicals. With increasing SDBS and Brij35 concentrations, volatilization rate constants (kC) of both Phe and Pyr initially decreased at fast rates and then at more moderate rates later on, resulting from the plasticizing effect of surfactants adsorbed on leaf surfaces. In addition, the photolysis rate constants (kP) decreased with the presence of SDBS but increased with the presence of Brij35. Overall, the total clearance rates of PAHs (kT) adsorbed onto living soybean leaf surfaces were inhibited by the presence of SDBS but promoted by the presence of Brij35. These observations show that surfactants may significantly alter the clearance of PAHs in agricultural systems, and the potential impact of surfactants on crop safety is closely related to surfactant types in natural environments. PMID- 26803790 TI - Higher concentrations of nanoscale zero-valent iron (nZVI) in soil induced rice chlorosis due to inhibited active iron transportation. AB - In this study, the effects of concentrations 0, 100, 250, 500, 750 and 1000 mg kg(-1) of nanoscale zero-valent iron (nZVI) on germination, seedlings growth, physiology and toxicity mechanisms were investigated. The results showed that nZVI had no effect on germination, but inhibited the rice seedlings growth in higher concentrations (>500 mg kg(-1) nZVI). The highest suppression rate of the length of roots and shoots reached 46.9% and 57.5%, respectively. The 1000mg kg( 1) nZVI caused the highest suppression rates for chlorophyll and carotenoids, at 91.6% and 85.2%, respectively. In addition, the activity of antioxidant enzymes was altered by the translocation of nanoparticles and changes in active iron content. Visible symptoms of iron deficiency were observed at higher concentrations, at which the active iron content decreased 61.02% in the shoots, but the active iron content not decreased in roots. Interestingly, the total and available amounts of iron in the soil were not less than those in the control. Therefore, the plants iron deficiency was not caused by (i) deficiency of available iron in the soil and (ii) restraint of the absorption that plant takes in the available iron, while induced by (iii) the transport of active iron from the root to the shoot was blocked. The cortex tissues were seriously damaged by nZVI which was transported from soil to the root, these were proved by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS). This current study shows that the mechanism of iron deficiency in rice seedling was due to transport of active iron from the root to the shoot blocked, which was caused by the uptake of nZVI. PMID- 26803792 TI - Biofouling on buoyant marine plastics: An experimental study into the effect of size on surface longevity. AB - Recent estimates suggest that roughly 100 times more plastic litter enters the sea than is found floating at the sea surface, despite the buoyancy and durability of many plastic polymers. Biofouling by marine biota is one possible mechanism responsible for this discrepancy. Microplastics (<5 mm in diameter) are more scarce than larger size classes, which makes sense because fouling is a function of surface area whereas buoyancy is a function of volume; the smaller an object, the greater its relative surface area. We tested whether plastic items with high surface area to volume ratios sank more rapidly by submerging 15 different sizes of polyethylene samples in False Bay, South Africa, for 12 weeks to determine the time required for samples to sink. All samples became sufficiently fouled to sink within the study period, but small samples lost buoyancy much faster than larger ones. There was a direct relationship between sample volume (buoyancy) and the time to attain a 50% probability of sinking, which ranged from 17 to 66 days of exposure. Our results provide the first estimates of the longevity of different sizes of plastic debris at the ocean surface. Further research is required to determine how fouling rates differ on free floating debris in different regions and in different types of marine environments. Such estimates could be used to improve model predictions of the distribution and abundance of floating plastic debris globally. PMID- 26803791 TI - Heavy metals in PM2.5 and in blood, and children's respiratory symptoms and asthma from an e-waste recycling area. AB - This study was to investigate the levels of heavy metals in PM2.5 and in blood, the prevalence of respiratory symptoms and asthma, and the related factors to them. Lead and cadmium in both PM2.5 and blood were significant higher in Guiyu (exposed area) than Haojiang (reference area) (p < 0.05), however, no significant difference was found for chromium and manganese in PM2.5 and in blood. The prevalence of cough, phlegm, dyspnea, and wheeze of children was higher in Guiyu compared to Haojiang (p < 0.05). No significant difference was found for the prevalence of asthma in children between Guiyu and Haojiang. Living in Guiyu was positively associated with blood lead (B = 0.196, p < 0.001), blood cadmium (B = 0.148, p < 0.05) and cough (OR, 2.37; 95% CI, 1.30-4.32; p < 0.01). Blood lead>5 MUg/dL was significantly associated with asthma (OR, 9.50; 95% CI, 1.16-77.49). Higher blood chromium and blood manganese were associated with more cough and wheeze, respectively. Our data suggest that living in e-waste exposed area may lead to increased levels of heavy metals, and accelerated prevalence of respiratory symptoms and asthma. PMID- 26803793 TI - Major correlates of mercury in small fish and common loons (Gavia immer) across four large study areas in Canada. AB - We investigated mercury (Hg) concentrations in small fish (mainly yellow perch, Perca flavescens; ~60% of fish collected) and in blood of common loons (Gavia immer) that prey upon them during the breeding season on lakes in 4 large, widely separated study areas in Canada (>13 lakes per study area; total number of lakes = 93). Although surface sediments from lakes near a base metal smelter in Flin Flon, Manitoba had the highest Hg concentrations, perch and other small fish and blood of common loon chicks sampled from these same lakes had low Hg concentrations similar to those from uncontaminated reference lakes. Multiple regression modeling with AIC analysis indicated that lake pH was by far the most important single factor influencing perch Hg concentrations in lakes across the four study areas (R(2) = 0.29). The best model was a three-variable model (pH + alkalinity + sediment Se; Wi = 0.61, R(2) = 0.85). A single-variable model (fish Hg) best explained among-lake variability in loon chick blood Hg (Wi = 0.17; R(2) = 0.53). From a toxicological risk perspective, all lakes posing a potential Hg health risk for perch and possibly other small pelagic fish species (where mean fish muscle Hg concentrations exceeded 2.4 MUg/g dry wt.), and for breeding common loons (where mean fish muscle Hg concentrations exceeded 0.8 MUg/g dry wt., and loon chick blood Hg exceeded 1.4 MUg/g dry wt.) had pH < 6.7 and were located in eastern Canada. PMID- 26803794 TI - Enhanced biocatalysis mechanism under microwave irradiation in isoquercitrin production revealed by circular dichroism and surface plasmon resonance spectroscopy. AB - An efficient and rapid process for isoquercitrin production by hesperidinase catalyzed hydrolysis of rutin was successfully developed under microwave irradiation detecting the affinity by circular dichroism (CD) and surface plasmon resonance (SPR) spectroscopy. A maximum isoquercitrin yield of 91.5+/-2.7% was obtained in 10min with the conditions of 10g/L hesperidinase, 2g/L rutin, 30 degrees C and microwave power density 88.9W/L. Enzymatic reaction rate and Vm/Km in the microwave reactor were 6.34-fold higher than in a continuous flow microreactor and 1.24-fold higher than in a biphasic system. CD and SPR analysis results also showed that hesperidinase has a better selectivity and affinity (3.3 fold than in a batch reactor) to generate isoquercitrin under microwave irradiation. Microwave irradiation greatly improved the reaction efficiency and productivity, leading to a more positive economical assessment. The binding affinity indicates the presence of strong multivalent interactions between rutin and hesperidinase under microwave irradiation. PMID- 26803795 TI - Metagenomic analysis of a desulphurisation system used to treat biogas from vinasse methanisation. AB - We investigated the response of microbial community to changes in H2S loading rate in a microaerated desulphurisation system treating biogas from vinasse methanisation. H2S removal efficiency was high, and both COD and DO seemed to be important parameters to biomass activity. DGGE analysis retrieved sequences of sulphide-oxidising bacteria (SOB), such as Thioalkalimicrobium sp. Deep sequencing analysis revealed that the microbial community was complex and remained constant throughout the experiment. Most sequences belonged to Firmicutes and Proteobacteria, and, to a lesser extent, Bacteroidetes, Chloroflexi, and Synergistetes. Despite the high sulphide removal efficiency, the abundance of the taxa of SOB was low, and was negatively affected by the high sulphide loading rate. PMID- 26803797 TI - Dynamic Iris Changes as a Risk Factor in Primary Angle Closure Disease. AB - PURPOSE: We studied the association between dynamic iris changes and the spectrum of primary angle closure disease (PACD), using the anterior segment optical coherence tomography (ASOCT). METHODS: Eligible primary angle closure (PAC), primary angle closure glaucoma (PACG), age, and sex comparable primary angle closure suspects (PACS) and normal subjects from the 5-year follow-up of the Handan Eye Study underwent ASOCT testing in dark and light conditions. The right eye of each subject was analyzed and biometric parameters including iris cross sectional area (IA), lens vault (LV), pupil diameter (PD), and centroid-to centroid distance (CCD) were calculated using the Zhongshan Angle Assessment Program. RESULTS: Totals of 31 PACS, 31 PAC/PACG, and 31 normal eyes were eligible for analysis. Loss of IA per mm PD increase in the dark compared to light was 0.18 mm in PACS, 0.13 mm in PAC/PACG, and 0.24 mm in normal (P = 0.015 between groups) groups. Diagnoses of normal (P = 0.001) and a smaller PD in light (P = 0.003) were statistically significant determinants of a larger IA loss per mm PD increase in the dark compared to light. Logistic regression analysis showed that LV (P = 0.002) and IA loss per mm PD increase (P = 0.017) were risk factors for an occludable angle. CONCLUSIONS: Significant differences in iris behavior in the dark compared to light in PACS, PACD, and normal eyes add to the evidence that dynamic iris change has a role in the pathogenesis of PAC in a rural Chinese population. PMID- 26803796 TI - The Effects of Diabetic Retinopathy and Pan-Retinal Photocoagulation on Photoreceptor Cell Function as Assessed by Dark Adaptometry. AB - PURPOSE: The pathophysiology of vision loss in persons with diabetic retinopathy (DR) is complex and incompletely defined. We hypothesized that retinal pigment epithelium (RPE) and rod and cone photoreceptor dysfunction, as measured by dark adaptometry, would increase with severity of DR, and that pan-retinal photocoagulation (PRP) would exacerbate this dysfunction. METHODS: Dark adaptation (DA) was measured in subjects with diabetes mellitus and healthy controls. Dark adaptation was measured at 5 degrees superior to the fovea following a flash bleach, and the data were analyzed to yield cone and rod sensitivity curves. Retinal layer thicknesses were quantified using spectral domain optical coherence tomography (OCT). RESULTS: The sample consisted of 23 controls and 73 diabetic subjects. Subjects with moderate nonproliferative diabetic retinopathy (NPDR) exhibited significant impairment of rod recovery rate compared with control subjects (P = 0.04). Cone sensitivity was impaired in subjects with proliferative diabetic retinopathy (PDR) (type 1 diabetes mellitus [T1DM]: P = 0.0047; type 2 diabetes mellitus [T2DM]: P < 0.001). Subjects with untreated PDR compared with subjects treated with PRP exhibited similar rod recovery rates and cone sensitivities. Thinner RPE as assessed by OCT was associated with slower rod recovery and lower cone sensitivity, and thinner photoreceptor inner segment/outer segment layer was associated with lower cone sensitivity. CONCLUSIONS: The results suggest that RPE and photoreceptor cell dysfunction, as assessed by cone sensitivity level and rod- and RPE-mediated dark adaptation, progresses with worsening DR, and rod recovery dysfunction occurs earlier than cone dysfunction. Function was preserved following PRP. The findings suggest multiple defects in retinoid function and provide potential points to improve visual function in persons with PDR. PMID- 26803798 TI - Measuring Corneal Haze by Using Scheimpflug Photography and Confocal Microscopy. AB - PURPOSE: We compared corneal backscatter estimated from a Scheimpflug camera with backscatter estimated from a clinical confocal microscope across a wide range of corneal haze. METHODS: A total of 59 corneas from 35 patients with a range of severity of Fuchs' endothelial corneal dystrophy and 15 corneas from 9 normal participants were examined using a Scheimpflug camera (Pentacam) and a confocal microscope (ConfoScan 4). The mean image brightness from the anterior 120 MUm, midcornea, and posterior 60 MUm of the cornea across the central 2 mm recorded by the Scheimpflug camera and analogous regions from the confocal microscope were measured and standardized. Differences between instruments and correlations between backscatter and disease severity were determined by using generalized estimating equation models. RESULTS: Backscatter measured by the two instruments in the anterior and midcornea were correlated (r = 0.67 and 0.43, respectively, P < 0.001), although in the posterior cornea they were not correlated (r = 0.13, P = 0.66). Measured with the Scheimpflug camera, mean backscatter from the anterior and midcornea were greater, whereas backscatter from the posterior cornea was lower (P < 0.001) than that measured by the confocal microscope. Backscatter from the anterior cornea was correlated with disease severity for both instruments (Scheimpflug, r = 0.55, P < 0.001; confocal, r = 0.49, P = 0.003). CONCLUSIONS: The Scheimpflug camera and confocal microscope should not be used interchangeably to measure corneal haze. The ability to detect changes in backscatter with disease severity is superior with the Scheimpflug camera. However, the confocal microscope provides higher resolution of corneal structure. PMID- 26803800 TI - Quantification of Vessel Density in Retinal Optical Coherence Tomography Angiography Images Using Local Fractal Dimension. AB - PURPOSE: To evaluate a fully automated local fractal dimension method to quantify vessel density and foveal avascular zone (FAZ) area in optical coherence tomography angiography (OCTA) images. METHODS: Fifty-two healthy Asian Indian eyes underwent imaging prospectively with OCTA system. Superficial and deep retinal vascular plexus was imaged. Local fractal analysis was applied to the OCTA images. A scan area of 3 * 3 mm was selected in the superficial and deep retinal layers. Foveal avascular zone area and vessel density were quantified in circular and sectoral zones around the fovea. A unique contour map of vessel density and dropout zones was developed to perform regional comparisons. RESULTS: Foveal avascular zone of superficial (0.35 +/- 0.013 mm2) and deep (0.49 +/- 0.012 mm2) retinal vascular plexus was segmented. The agreement between the manually segmented and local fractal dimension segmented FAZ area was 0.97 (95% confidence interval [CI]: 0.94-0.98) and did not change significantly with age (P = 0.94 and 0.21, respectively). The vessel density was greater in the deep than the superficial retinal vascular plexus (P < 0.0001). When the image was subdivided into sectors around the FAZ, inferior sector had greater vessel density than the others (temporal, superior, and nasal) in both superficial and deep retinal vascular plexus (P < 0.05). These observations were similar to recent studies on animal retinal vasculature map. CONCLUSIONS: A novel implementation of local fractal dimension to calculate vessel density and FAZ area was demonstrated. Age did not impact vessel density but sectoral analyses showed greater vessel density in the inferior zone. PMID- 26803799 TI - Use and Misuse of Laplace's Law in Ophthalmology. AB - PURPOSE: Laplace's Law, with its compactness and simplicity, has long been employed in ophthalmology for describing the mechanics of the corneoscleral shell. We questioned the appropriateness of Laplace's Law for computing wall stress in the eye considering the advances in knowledge of ocular biomechanics. METHODS: In this manuscript we recapitulate the formulation of Laplace's Law, as well as common interpretations and uses in ophthalmology. Using numerical modeling, we study how Laplace's Law cannot account for important characteristics of the eye, such as variations in globe shape and size or tissue thickness, anisotropy, viscoelasticity, or that the eye is a living, dynamic organ. RESULTS: We show that accounting for various geometrical and material factors, excluded from Laplace's Law, can alter estimates of corneoscleral wall stress as much as 456% and, therefore, that Laplace's Law is unreliable. CONCLUSIONS: We conclude by illustrating how computational techniques, such as finite element modeling, can account for the factors mentioned above, and are thus more suitable tools to provide quantitative characterization of corneoscleral biomechanics. PMID- 26803801 TI - Engaging primary healthcare nurses in men's health education: A pilot study. AB - Many countries have identified a need for targeted men's health promotion within primary health care as part of broader men's health policy. Primary health care nurses are well placed to deliver such services but may lack the requisite skills. The aim of this study was to pilot the delivery phase of an education program and evaluate a train-the-trainer approach for delivering men's health education to primary health care nurses. The 8-h train-the-trainer workshop was designed to equip nurses to deliver men's health education workshops to peers. Surveys of facilitators (n = 18) and peer workshop participants (n = 98) evaluated their level of confidence in men's health and knowledge and skills in men's health promotion. After completing the train-the-trainer workshop, most facilitators expressed confidence (92%), and all indicated sufficient knowledge and access to resources to deliver a peer workshop. All agreed that the module was sufficiently flexible to suit their local setting. Following the peer education workshop, facilitators and workshop participants reported high levels of confidence and knowledge in men's health promotion. This pilot evaluation suggests train-the-trainer is an effective model to deliver men's health education across a range of settings, with a flexible approach to raising awareness and improving the skills of primary health care nurses in men's health promotion. PMID- 26803802 TI - Learning and choosing in an uncertain world: An investigation of the explore exploit dilemma in static and dynamic environments. AB - How do people solve the explore-exploit trade-off in a changing environment? In this paper we present experimental evidence from an "observe or bet" task, in which people have to determine when to engage in information-seeking behavior and when to switch to reward-taking actions. In particular we focus on the comparison between people's behavior in a changing environment and their behavior in an unchanging one. Our experimental work is motivated by rational analysis of the problem that makes strong predictions about information search and reward seeking in static and changeable environments. Our results show a striking agreement between human behavior and the optimal policy, but also highlight a number of systematic differences. In particular, we find that while people often employ suboptimal strategies the first time they encounter the learning problem, most people are able to approximate the correct strategy after minimal experience. In order to describe both the manner in which people's choices are similar to but slightly different from an optimal standard, we introduce four process models for the observe or bet task and evaluate them as potential theories of human behavior. PMID- 26803803 TI - CryoEM structures of two spliceosomal complexes: starter and dessert at the spliceosome feast. AB - The spliceosome is formed on pre-mRNA substrates from five small nuclear ribonucleoprotein particles (U1, U2, U4/U6 and U5 snRNPs), and numerous non-snRNP factors. Saccharomyces cerevisiae U4/U6.U5 tri-snRNP comprises U5 snRNA, U4/U6 snRNA duplex and approximately 30 proteins and represents a substantial part of the spliceosome before activation. Schizosaccharomyces pombe U2.U6.U5 spliceosomal complex is a post-catalytic intron lariat spliceosome containing U2 and U5 snRNPs, NTC (nineteen complex), NTC-related proteins (NTR), U6 snRNA, and an RNA intron lariat. Two recent papers describe near-complete atomic structures of these complexes based on cryoEM single-particle analysis. The U4/U6.U5 tri snRNP structure provides crucial insight into the activation mechanism of the spliceosome. The U2.U6.U5 complex reveals the striking architecture of NTC and NTR and important features of the group II intron-like catalytic RNA core remaining after spliced mRNA is released. These two structures greatly advance our understanding of the mechanism of pre-mRNA splicing. PMID- 26803804 TI - Active packaging with antifungal activities. AB - There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time. PMID- 26803806 TI - Assessing the Ecological Response of Dung Beetles in an Agricultural Landscape Using Number of Individuals and Biomass in Diversity Measures. AB - The global increase in demand for productive land requires us to increase our knowledge of the value of agricultural landscapes for the management and conservation of biodiversity, particularly in tropical regions. Thus, comparative studies of how different community attributes respond to changes in land use under different levels of deforestation intensity would be useful. We analyzed patterns of dung beetle diversity in an Andean region dominated by sun-grown coffee. Diversity was estimated using two measures of species abundance (the number of individuals and biomass) and was compared among four types of vegetation cover (forest, riparian forest, sun-grown coffee, and pastures) in three landscape plots with different degrees of deforestation intensity (low, intermediate, and high). We found that dung beetle diversity patterns differed between types of vegetation cover and degree of deforestation, depending on whether the number of individuals or biomass was used. Based on biomass, inequality in the dung beetle community was lowest in the forest, and increased in the sun-grown coffee and pastures across all levels of deforestation, particularly for the increasing dominance of large species. The number of beetles and biomass indicate that the spatial dominance of sun-grown coffee does not necessarily imply the drastic impoverishment of dung beetle diversity. In fact, for these beetles, it would seem that the landscape studied has not yet crossed "a point of no return." This system offers a starting point for exploring biodiversity management and conservation options in the sun-grown coffee landscapes of the Colombian Andes. PMID- 26803805 TI - Energy Contents of Frequently Ordered Restaurant Meals and Comparison with Human Energy Requirements and U.S. Department of Agriculture Database Information: A Multisite Randomized Study. AB - BACKGROUND: Excess energy intake from meals consumed away from home is implicated as a major contributor to obesity, and ~50% of US restaurants are individual or small-chain (non-chain) establishments that do not provide nutrition information. OBJECTIVE: To measure the energy content of frequently ordered meals in non-chain restaurants in three US locations, and compare with the energy content of meals from large-chain restaurants, energy requirements, and food database information. DESIGN: A multisite random-sampling protocol was used to measure the energy contents of the most frequently ordered meals from the most popular cuisines in non-chain restaurants, together with equivalent meals from large-chain restaurants. SETTING: Meals were obtained from restaurants in San Francisco, CA; Boston, MA; and Little Rock, AR, between 2011 and 2014. MAIN OUTCOME MEASURES: Meal energy content determined by bomb calorimetry. STATISTICAL ANALYSIS PERFORMED: Regional and cuisine differences were assessed using a mixed model with restaurant nested within region*cuisine as the random factor. Paired t tests were used to evaluate differences between non-chain and chain meals, human energy requirements, and food database values. RESULTS: Meals from non-chain restaurants contained 1,205+/-465 kcal/meal, amounts that were not significantly different from equivalent meals from large-chain restaurants (+5.1%; P=0.41). There was a significant effect of cuisine on non-chain meal energy, and three of the four most popular cuisines (American, Italian, and Chinese) had the highest mean energy (1,495 kcal/meal). Ninety-two percent of meals exceeded typical energy requirements for a single eating occasion. CONCLUSIONS: Non-chain restaurants lacking nutrition information serve amounts of energy that are typically far in excess of human energy requirements for single eating occasions, and are equivalent to amounts served by the large-chain restaurants that have previously been criticized for providing excess energy. Restaurants in general, rather than specific categories of restaurant, expose patrons to excessive portions that induce overeating through established biological mechanisms. PMID- 26803808 TI - Radiation de-intensification for patients with glioblastoma and poor prognostic features--how much do we really know? PMID- 26803807 TI - Co-expression of phenylalanine hydroxylase variants and effects of interallelic complementation on in vitro enzyme activity and genotype-phenotype correlation. AB - BACKGROUND: In phenylketonuria (PKU) patients, the combination of two phenylalanine hydroxylase (PAH) alleles is the main determinant of residual enzyme activity in vivo and in vitro. Inconsistencies in genotype-phenotype correlations have been observed in compound heterozygous patients and a particular combination of two PAH alleles may produce a phenotype that is different from the expected one, possibly due to interallelic complementation. METHODS: A dual eukaryotic vector system with two distinct PAH proteins N terminally fused to different epitope tags was used to investigate the co expression of PAH alleles reported in patients with inconsistent phenotypes. PAH variant proteins were transiently co-transfected in COS-7 cells. PAH activity was measured by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS), and protein expression was measured by Western blot. Genotypes were compared with predicted PAH activity from the PAH locus-specific database (PAHvdb) and with phenotypes and tetrahydrobiopterin (BH4) responsiveness from more than 10,000 PKU patients (BIOPKU database). RESULTS: Through the expression and co-expression of 17 variant alleles we demonstrated that interallelic interaction could be both positive and negative. The co expressions of p.[I65T];[R261Q] (19.5% activity; predicted 43.5%) and p.[I65T];[R408W] (15.0% vs. 26.8% activity) are examples of genotypes with negative interallelic interaction. The co-expressions of p.[E178G];[Q232E] (55.0% vs.36.4%) and p.[P384S];[R408W] (56.1% vs. 40.8%) are examples of positive subunit interactions. Inconsistencies of PAH residual enzyme activity in vitro and of PKU patients' phenotypes were observed as well. The PAH activity of p.[R408W];[A300S] is 18.0% of the wild-type activity; however, 88% of patients with this genotype exhibit mild hyperphenylalaninemias (MHPs). CONCLUSION: The co expression of two distinct PAH variants revealed possible dominance effects (positive or negative) by one of the variants on residual PAH activity as a result of interallelic complementation. PMID- 26803809 TI - Predicting glioblastoma response to bevacizumab through marker profiling? PMID- 26803811 TI - Molecular portrait of a rare case of metastatic glioblastoma: somatic and germline mutations using whole-exome sequencing. PMID- 26803813 TI - The neuritogenic and neuroprotective potential of senegenin against Abeta-induced neurotoxicity in PC 12 cells. AB - BACKGROUND: Improved therapeutics aimed at ameliorating the devastating effects of neurodegenerative diseases, such as Alzheimer's disease (AD), are pertinent to help attenuate their growing prevalence worldwide. One promising avenue for such therapeutics lies in botanical medicines that have been efficaciously employed in the likes of traditional medicine doctrines for millennium. Integral to this approach is the necessity of neuritogenesis and/or neuroprotection to counterbalance the deleterious effects of amyloid-beta (Abeta) proteins. Senegenin, a principle saponin of Polygala tenuifolia Willd., which has empirically shown to improve cognition and intelligence, was chosen to evaluate its cytoprotective potential and possible neuritogenic and neuroprotective effects. METHODS: The purpose of the present study was then to analyze morphological changes in neurite development and altered protein expression of two proteins requisite to neuritogenesis, growth associated protein 43 (Gap-43) and microtubule-associated protein 2 (MAP2) in PC 12 cells. Neuritogenic analysis was conducted with immunofluorescence after incubation with Abeta (25-35) peptide, and to deduce information on cell viability and mitochondrial functionality MTT (3,(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) was employed. RESULTS: This study found that cells pre-incubated with senegenin for 24 h (40 MUg and 20 MUg/ml) before introducing Abeta attenuated Abeta cytotoxicity, and significantly increased cell viability by 23 % and 34 % (P < 0.001), respectively. In neurite outgrowth experiments, Abeta was compared to NGF positive control and senegenin treated groups which showed a drastic decrease in the quantity, average length and maximum length of neurites (P < 0.001). At concentrations of 1 MUg/ml (P < 0.01) and 5 MUg/ml (P < 0.05) senegenin triggered neuritogenesis with significant increases in total neurite number, average length and maximum length. This was additionally shown through the augmented expression of MAP2 and Gap-43. CONCLUSIONS: These results suggest that senegenin possesses cytoprotective properties, can moderate neurite outgrowth and augment MAP2 and Gap-43, thus suggesting a potential therapeutic value for Polygala tenuifolia in neurodegenerative disorders. PMID- 26803815 TI - Changes in the Russian Wheat Aphid (Hemiptera: Aphididae) Biotype Complex in South Africa. AB - Russian wheat aphid Diuraphis noxia (Kurdjumov) has spread from its native area in central Asia to all the major wheat-producing countries in the world to become an international wheat pest. Because the Russian wheat aphid is a serious threat to the wheat industry in South Africa, it is important to investigate the key factors involved in the distribution of Russian wheat aphid biotypes and in the changes of the Russian wheat aphid biotype complex in South Africa. There are currently four known Russian wheat aphid biotypes occurring in South Africa. Russian wheat aphid samples were collected from 2011 to 2014 during the wheat growing season in spring and summer and these samples were screened to determine the biotype status. RWASA1 occurred predominantly in the Western Cape, while RWASA2 and RWASA3 occurred predominantly in the Eastern Free State. Following the first record of RWASA4 in 2011, this biotype was restricted to the Eastern Free State. The surveys suggest that the Russian wheat aphid bioype complex was more diverse in the Eastern Free State than in the other wheat production areas. There was also a shift in Russian wheat aphid biotype composition over time. The Russian wheat aphid biotype complex is dynamic, influenced by environmental factors such as host plants, altitude, and climate, and it can change and diversify over time causing fluctuation in populations over sites and years. This dynamic nature of the Russian wheat aphid will continue to challenge the development of Russian wheat aphid-resistant wheat cultivars in South Africa, and the continued monitoring of the biotypic and genetic structure, to determine genetic relatedness and variation in different biotypes, of Russian wheat aphid populations is important for protecting wheat. PMID- 26803814 TI - Cost-effectiveness of HPV vaccination regime: comparing twice versus thrice vaccinations dose regime among adolescent girls in Malaysia. AB - BACKGROUND: The HPV vaccine was introduced to Malaysian national immunization programme in 2010. The current implementation age of HPV vaccination in Malaysian is at the age of 13 years school girls, given according to a 3 doses protocol which may complicate implementation and compliance. Aim of the study is to determine the cost-effectiveness of HPV vaccination regime comparing twice versus thrice HPV vaccinations dose regime among adolescent girls in Malaysia. METHODS: A Markov cohort model reflecting the natural history of HPV infection accounting for oncogenic and low-risk HPV was adapted for 13 year old Malaysian girls cohort (n = 274,050). Transition probabilities, utilities values, epidemiological and cost data were sourced from published literature and local data. Vaccine effectiveness was based on overall efficacy reported from 3-doses clinical trials, with the assumption that the 2-doses is non-inferior to the 3-doses allowing overall efficacy to be inferred from the 3-doses immunogenicity data. Price parity and life-long protection were assumed. The payer perspective was adopted, with appropriate discounting for costs (3 %) and outcomes (3 %). One way sensitivity analysis was conducted. The sensitivity analysis on cost of vaccine, vaccine coverage and discount rate with a 2-doses protocol was performed. RESULT: The 3-doses and 2-doses regimes showed same number of Cervical Cancers averted (361 cases); QALYs saved at 7,732,266. However, the lifetime protection under the 2-doses regime, showed a significant cost-savings of RM 36, 722,700 compared to the 3-doses scheme. The MOH Malaysia could vaccinate 137,025 more girls in this country using saving 2-doses regime vaccination programme. The model predicted that 2-doses HPV vaccination schemes can avoid additional 180 Cervical Cancers and 63 deaths compare to 3-doses. CONCLUSION: A 2-doses HPV vaccination scheme may enable Malaysian women to be protected at a lower cost than that achievable under a 3-doses scheme, while avoiding the same number of Cervical Cancer cases and deaths. Using the saving money with 2-doses, more Cervical Cancers and deaths can be avoided. PMID- 26803816 TI - Responses by Dendroctonus frontalis and Dendroctonus mesoamericanus (Coleoptera: Curculionidae) to Semiochemical Lures in Chiapas, Mexico: Possible Roles of Pheromones During Joint Host Attacks. AB - In southern Mexico and Central America, the southern pine beetle Dendroctonus frontalis Zimmermann (Coleoptera: Curculionidae: Scolytinae) commonly colonizes host trees simultaneously with Dendroctonus mesoamericanus Armendariz-Toledano and Sullivan, a recently described sibling species. We hypothesized that cross species pheromone responses by host-seeking beetles might mediate joint mass attack, bole partitioning, and reproductive isolation between the species. Previous studies had indicated that D. frontalis females produce frontalin and that female D. mesoamericanus produce frontalin, endo-brevicomin, and ipsdienol (males of both species produce endo-brevicomin and possibly ipsdienol). In field trapping trials in the Mexican state of Chiapas, D. frontalis was attracted to the lure combination of turpentine and racemic frontalin; racemic endo-brevicomin enhanced this response. In a single test, D. mesoamericanus was attracted in low numbers to the combination of turpentine, racemic frontalin, and racemic endo brevicomin after the addition of racemic ipsdienol; in contrast, racemic ipsdienol reduced responses of D. frontalis. Inhibition of D. frontalis was generated in both sexes by (+)- and racemic ipsdienol, but by (-)-ipsdienol only in females. Logs infested with D. mesoamericanus females (the pioneer sex in Dendroctonus) attracted both species in greater numbers than either D. frontalis female-infested or uninfested logs. Our data imply that D. frontalis may be more attracted to pioneer attacks of D. mesoamericanus females, and that this could be owing to the presence of endo-brevicomin in the latter. Possible intra- and inter specific functions of semiochemicals investigated in our experiments are discussed. PMID- 26803817 TI - Effects of Kaolin on Lobesia botrana (Lepidoptera: Tortricidae) and Its Compatibility With the Natural Enemy, Trichogramma cacoeciae (Hymenoptera: Trichogrammatidae). AB - Lobesia botrana (Denis and Schiffermuller) (Lepidoptera: Tortricidae) is an important grapevine pest in Europe recently encountered in America. Trichogramma cacoeciae Marchal (Hymenoptera: Trichogrammatidae) is amongst the most effective parasitoids for Lepidopteran species. Studies to evaluate the effect of kaolin, an inert, nontoxic mineral, on oviposition, egg hatch, and neonate mortality of these species were carried out. Efficacy on L. botrana neonate larvae, oviposition, and egg hatch was evaluated. Effects of kaolin on parasitism and emergence of T. cacoeciae from L. botrana and Ephestia kuehniella (Zeller) (Lepidoptera: Pyralidae) eggs were also evaluated. Lobesia botrana egg hatch and oviposition rates were reduced, and neonate larvae mortality was significantly greater in kaolin-treated arenas and when included in synthetic neonate larvae diet. Kaolin had no effect on T. cacoeciae parasitism in both hosts. There was only a slight but statistically insignificant effect on T. cacoeciae progeny emergence from L. botrana eggs and no effect from E. kuehniella. The results involving reductions in L. botrana oviposition and egg hatch and increase in larval mortality with kaolin suggest this compound may contribute to reduction in population densities and can be considered in rational integrated pest management strategies for L. botrana. Due to the laboratory results presented on parasitoid emergence, even though field bioassays would give a more exhaustive evaluation, it appears kaolin can be compatible with T. cacoeciae in L. botrana management. PMID- 26803819 TI - Absolute Stereochemistry of 1,2-Diols from Lipids of Thermomicrobia. AB - 1,2-Diol based phospholipids are a well-known feature of bacteria from the class Thermomicrobia. Since these bacteria contain only lipids with an alkyldiol-1 phosphate backbone instead of sn-glycero-3-phosphate, it is important to elucidate the stereochemistry of the 1,2-diols. We have studied the absolute stereochemistry of long-chain 1,2-diols isolated from Thermorudis pharmacophila (formerly known as Thermomicrobia sp. WKT50.2) by nuclear magnetic resonance (NMR) using alpha-methoxyphenylacetic acid (MPA). Low-temperature (-60 degrees C) NMR of bis-(R)-MPA ester showed (R) stereochemistry of the 1,2-diols. This is the first report concerning the stereochemistry of natural 1,2-diols, which replace the glyceride moiety in phospholipids. The (R) stereochemistry of the diols is expected as it is the same configuration as for the common bacterial lipid backbone-sn-glycero-3-phosphate. This is the first application of low temperature NMR of a single MPA derivative for assignment of stereochemistry of natural 1,2-diols. The results were confirmed by the comparison of NMR data with bis-(R)-MPA ester of (R) and rac-1,2-octanediol. PMID- 26803818 TI - Altered left ventricular performance in aging physically active mice with an ankle sprain injury. AB - We assessed the impact of differing physical activity levels throughout the lifespan, using a musculoskeletal injury model, on the age-related changes in left ventricular (LV) parameters in active mice. Forty male mice (CBA/J) were randomly placed into one of three running wheel groups (transected CFL group, transected ATFL/CFL group, SHAM group) or a SHAM Sedentary group (SHAMSED). Before surgery and every 6 weeks after surgery, LV parameters were measured under 2.5 % isoflurane inhalation. Group effects for daily distance run was significantly greater for the SHAM and lesser for the ATLF/CFL mice (p = 0.013) with distance run decreasing with age for all mice (p < 0.0001). Beginning at 6 months of age, interaction (group * age) was noted with LV posterior wall thickness-to-radius ratios (h/r) where h/r increased with age in the ATFL/CFL and SHAMSED mice while the SHAM and CFL mice exhibited decreased h/r with age (p = 0.0002). Passive filling velocity (E wave) was significantly greater in the SHAM mice and lowest for the ATFL/CFL and SHAMSED mice (p < 0.0001) beginning at 9 months of age. Active filling velocity (A wave) was not different between groups (p = 0.10). Passive-to-active filling velocity ratio (E/A ratio) was different between groups (p < 0.0001), with higher ratios for the SHAM mice and lower ratios for the ATFL/CFL and SHAMSED mice in response to physical activity beginning at 9 months of age. Passive-to-active filling velocity ratio decreased with age (p < 0.0001). Regular physical activity throughout the lifespan improved LV structure, passive filling velocity, and E/A ratio by 6 to 9 months of age and attenuated any negative alterations throughout the second half of life. The diastolic filling differences were found to be significantly related to the amount of activity performed by 9 months and at the end of the lifespan. PMID- 26803820 TI - Knowledge, Perception, and Attitudes of Cancer Patients Towards Cancer and Cancer Care: Local Perspective from Saudi Arabia. AB - Understanding the attitudes of cancer patients towards different cancer-related issues is very important for the health care provider in order to deliver an optimal care. This survey was designed to collect data about the initial patient's perception and reaction to the diagnosis of cancer, the patient's preference regarding the disclosure of diagnosis, and prevalence and pattern of complementary and alternative medicine (CAM) use. Between January and December 2011, of 234 cancer patients, 42.2 % believed that eye of evil/envy was the cause of their cancers. In 18.3 % of cases, relatives refused to inform the patient about the diagnosis. Participants liked to be the first to be informed, either with relatives at the same time (44.21 %) or alone (33.48 %). Only 7.7 % of participants liked to totally leave decisions to their doctors and/or relatives. There were 53.4 % tried CAM before starting treatment, and 46.7 % continued using CAM during treatment and most of them used more than one type of CAM. Treatment with the Holy Qur'an or Ruqia was widely reported by the study population (92 %). Our survey confirmed that the patient's preference is towards disclosure while the public attitude is, relatively, still against full disclosure. This situation poses a special challenge to the physicians in Kingdom of Saudi Arabia (KSA) when it comes to discussing the disease and treatment. Educational efforts are required to emphasize the curative role of conventional treatment, especially surgery, in many cases. Such efforts should also address the wrong beliefs and misconceptions regarding CAM. PMID- 26803821 TI - Digital antimicrobial susceptibility testing using the MilliDrop technology. AB - We present the MilliDrop Analyzer (MDA), a droplet-based millifluidic system for digital antimicrobial susceptibility testing (D-AST), which enables us to determine minimum inhibitory concentrations (MICs) precisely and accurately. The MilliDrop technology was validated by using resazurin for fluorescence readout, for comparison with standard methodology, and for conducting reproducibility studies. In this first assessment, the susceptibility of a reference Gram negative strain Escherichia coli ATCC 25922 to gentamicin, chloramphenicol, and nalidixic acid were tested by the MDA, VITEK(r)2, and broth microdilution as a reference standard. We measured the susceptibility of clinically relevant Gram positive strains of Staphylococcus aureus to vancomycin, including vancomycin intermediate S. aureus (VISA), heterogeneous vancomycin-intermediate S. aureus (hVISA), and vancomycin-susceptible S. aureus (VSSA) strains. The MDA provided results which were much more accurate than those of VITEK(r)2 and standard broth microdilution. The enhanced accuracy enabled us to reliably discriminate between VSSA and hVISA strains. PMID- 26803826 TI - Abstracts: ASCPT 2016 Annual Meeting & Quantitative Translational Approaches in Oncology Pre-Conference. PMID- 26803822 TI - Outbreak of NDM-1-producing Klebsiella pneumoniae ST76 and ST37 isolates in neonates. AB - The purpose of this study was to investigate the epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) in Shanghai Children's Hospital in China. Twenty-two non-duplicate CRKP strains were collected from pediatric patients between March and June in 2014. Antimicrobial susceptibility testing was conducted by the agar dilution method. Beta-lactamases were characterized by polymerase chain reaction (PCR) and DNA sequencing. The transferability of bla NDM-1 was investigated by conjugation experiment. The plasmids bearing antibiotic resistance genes were characterized by S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern hybridization. Clonal relatedness was evaluated by PFGE and multilocus sequence typing (MLST). The clinical data of patients were retrospectively reviewed. The 22 CRKP strains were resistant to most of the antimicrobial agents tested, except tigecycline and colistin. Overall, 59, 77, and 100 % of these strains were resistant to imipenem, meropenem, and ertapenem, respectively. The bla NDM-1 was positive in 77.3 % (17/22) of the CRKP strains, of which the 16 isolates from inpatients were designated as ST37 (n = 9) and ST76 (n =7) and one isolate from an outpatient belonged to ST846. The 17 bla NDM-1-positive isolates belonged to PFGE type A (n = 9), type C (n = 7), or type B (n = 1). The plasmids bearing bla NDM-1 could be transferred into recipient Escherichia coli J53 through conjugation in 88.2 % (15/17) of the strains. The hybridization results showed that the plasmids carrying the bla NDM-1 gene were approximately 50-240 kb in size. This is the first report of an outbreak caused by NDM-1-producing K. pneumoniae ST76 and ST37 among neonates. PMID- 26803828 TI - Introduction to special section on patient-reported outcomes in nonstandard settings. PMID- 26803827 TI - Cystoid macular lesions are resistant to topical dorzolamide treatment in enhanced S-cone syndrome child. AB - PURPOSE: To evaluate whether cystoid macular lesions respond to treatment with dorzolamide 2% drops in the enhanced S-cone syndrome (ESCS) child, as several case reports document favorable efficacy in adults. METHODS: Seven-year-old boy with ESCS and cystoid macular lesions was treated with dorzolamide 2% in both eyes three times a day for a period of 7 months. The efficacy of treatment was analyzed by visual acuity assessment (ETDRS), multifocal electroretinography and SD-OCT central foveal thickness (CFT) measurement. RESULTS: Baseline RE CFT was 540 and 453 um in the LE, with amplitude of P1-wave density 39.8 and 50.4 nV/deg(2), respectively. Best corrected visual acuity (BCVA) was 0.3 logMAR RE and 0.3 logMAR LE at distance. At 7-month follow-up examination, CFT showed no reduction in thickness (RE 599 um, LE 521 um). P1-wave density increased (RE 49.1 nV/deg(2), LE 84.9 nV/deg(2)), with BCVA 0.3 logMAR RE and 0.2 logMAR LE. CONCLUSIONS: To the best of our knowledge, this is the youngest ESCS patient treated with dorzolamide drops and the first report recording that cystoid macular lesions are resistant to topical dorzolamide treatment. Furthermore, these data are in favor of the hypothesis that microcystoid changes in ESCS appear due to defects in cell-to-cell adhesion rather than the disintegration of the retinal barrier. The marked differences in treatment response to carbonic anhydrase inhibitors between the adults and the child here presented suggest that the breakdown of the blood-retinal barrier may play a more important role later in life. PMID- 26803829 TI - Analyzing Long-Duration and High-Frequency Data Using the Time-Varying Effect Model. AB - With the rapid development of methods for electronic data capture, longitudinal data sets with many assessment points have become common in mental health services and addiction research. These data typically exhibit complex and irregular patterns of change, and the relationship between variables may also change over time. Existing statistical methods are not flexible enough to capture this complexity, but a new method, the time-varying effect model (TVEM), permits modeling nearly any shape of change, and allows the effect of an independent variable on outcome to change over time. This paper introduces TVEM and illustrates its application using data from a 16-year study of 223 participants with serious mental illness and substance abuse. PMID- 26803830 TI - Landing on branches in the frog Trachycephalus resinifictrix (Anura: Hylidae). AB - Frogs (Lissamphibia: Anura) are famous for their saltatory or hopping locomotion, which is related to numerous anatomical specialisations that are characteristic for the group. However, while the biomechanics of take-off in frogs have been studied in detail, much less is known on how frogs land after a jump. Besides terrestrial and aquatic species, several lineages of frogs adopted an arboreal lifestyle and especially the biomechanics of landing on challenging, small, and unpredictable substrates, such as leaves or branches, are virtually unknown. Here we studied the landing kinematics of the arboreal frog Trachycephalus resinifictrix (Hylidae) on a wooden stick that was used to mimic a small tree branch. We observed two different landing behaviours: (1) landing on the abdomen and (2) attachment with the toes of either the forelimb or the hindlimb. In the latter case, the frogs performed a cartwheel around the stick, while they were only attached by their adhesive toe pads. We estimated the forces that act on the toes during this behaviour to be up to fourteen times the body weight of the animals. This behaviour demonstrates the remarkable adhesive capabilities of the toe pads and the body control of the frogs. PMID- 26803831 TI - The SRAP based molecular diversity related to antifungal and antioxidant bioactive constituents for biocontrol potentials of Trichoderma against Sclerotium rolfsii Scc. AB - The study was performed to examine 11 isolates of Trichoderma for their bio control potentials against Sclerotium rolfsii Sacc. causing stem rot in groundnut. The antagonists Trichoderma were subjected to sequence related amplified polymorphism (SRAP) based molecular diversity analysis and compared with their hardness to S. rolfsii with respect to secretary antifungal and antioxidant profile. T. virens NBAII Tvs 12 evident highest (87.91 %) growth inhibition of test pathogen followed by T. koningii MTCC 796 (67.03 %) at 7 days after inoculation (DAI). Microscopic study confirmed biocontrol mechanism as mycoparasitism for Tvs 12 and antibiosis for MTCC 796. The growth inhibition of test pathogen was significantly negatively correlated with sclerotia formation and lipid peroxidation during antagonism due to release of secretary bioactive antioxidants by antagonists to terminate oxidative burst generated by S. rolfsii and causing inhibition of sclerotium formation. The GC-MS profile identified antifungal and antioxidant constituents hexadecane, 1,2-benzenedicarboxylic acid, mono (2-ethylhexyl) ester, 1-hexadecanesulfonyl chloride, and octadecane in potent antagonists Tvs 12; and nonacosane and octadecane in MTCC 796 along with two novel compounds 1-pentadecene and 1-heneicosyl formate for biocontrol activity. Molecular diversity of Trichoderma isolates associated with antagonistic activity was assessed by SRAP markers. The 115 primer combinations generate total 1328 amplified products of which, 1095 are shared polymorphic and 199 are unique polymorphic. The 15 SRAP combinations produced 18 bands to diagnose best antagonist Tvs 12 and 13 SRAP combinations generated 19 unique bands for identification of MTCC 796. The mycoparasitic antagonist Tvs 12 would be the best antagonist and released unique antifungal and antioxidant constituents to combat pathogen infection. The SRAP based genetic diversity indicates Tvs12 strain clustered with T. viride NBAII Tv23 and shared only 52 % similarity with other isolates of Trichoderma. The SRAP similarities explained substantial diversity (19-68 %) across Trichoderma isolates. PMID- 26803832 TI - Non-compaction cardiomyopathy. PMID- 26803833 TI - Psychosocial and physical outcomes of in- and outpatient rehabilitation in prostate cancer patients treated with radical prostatectomy. AB - PURPOSE: A radical prostatectomy might lead to an impaired quality of life. Aim of the study was to analyse the impact of inpatient and outpatient rehabilitation on psychosocial and physical outcomes in patients after surgery. METHODS: Six hundred nineteen inpatients and 95 outpatients, treated for localized prostate cancer by prostatectomy, completed the Hospital Anxiety and Depression Scale (HADS) and two quality-of-life questionnaires (EORTC QLQ-C30 and EORTC QLQ-PR25) at the beginning and end of rehabilitation as well as 12 months after rehabilitation. Data were analysed by using t-tests, chi(2) - tests and analyses of variance with repeated measures. RESULTS: Compared to a population sample, patients reported a significantly worse quality of life (EORTC QLQ-C30) and more anxiety (HADS) at the beginning of rehabilitation. Physical, role and social functioning increased significantly over time for in- and outpatients. Patients still reported lower emotional functioning (EORTC QLQ-C30), anxiety (HADS) and prostate cancer-specific physical symptoms (EORTC QLQ-PR25) 1 year after rehabilitation, although symptom levels decreased significantly over time. The setting did not have an independent significant effect in the multivariate model. CONCLUSIONS: In- and outpatients reported an increased quality of life 1 year after rehabilitation with respect to their physical constitution and their reintegration into social life. Nonetheless, both groups still struggled with problems due to surgery. The results indicated that both settings seem to be supportive in the recovery process but that patients seem to require additional support with aftercare for treating surgery-related problems as well as emotional discomfort. PMID- 26803834 TI - Designing an integrative gynecologic oncology model of supportive care: call for a cross-cultural international collaboration. PMID- 26803835 TI - Predicting early post-chemotherapy adverse events in patients with hematological malignancies: a retrospective study. AB - PURPOSE: The purpose of this study was to develop a mathematical model that predicts the definite adverse events following chemotherapy in patients with hematological malignancies (HMs). METHODS: This is a retrospective cohort study including 1157 cases with HMs. Firstly, we screened and verified the independent risk factors associated with post-chemotherapy adverse events by both univariate and multivariate logistic regression analysis using 70 % of randomly selected cases (training set). Secondly, we proposed a mathematical model based on those selected factors. The calibration and discrimination of the model were assessed by Hosmer-Lemeshow (H-L) test and area under the receiver operating characteristic (ROC) curve, respectively. Lastly, the predicative power of this model was further tested in the remaining 30 % of cases (validation set). RESULTS: Our statistical analysis indicated that liver dysfunction (OR = 2.164), active infection (OR = 3.619), coagulation abnormalities (OR = 4.614), intensity of chemotherapy (OR = 10.001), acute leukemia (OR = 2.185), and obesity (OR = 1.604) were independent risk factors for post-chemotherapy adverse events in HM patients (all P < 0.05). Based on the verified risk factors, a predictive model was proposed. This model had good discrimination and calibration. When 0.648 was selected as the cutoff point, the sensitivity and specificity of this predictive model in validation sets was 72.7 and 87.4 %, respectively. Furthermore, this proposed model's positive predictive value, negative predictive value, and consistency rate were 87.3, 73.0 and 80.0 %, respectively. CONCLUSIONS: Our study indicated that this six risk factor-based mathematical model is accurate and sufficient enough to predict definite post-chemotherapy adverse events in a HM patient and it may aid clinicians to optimize treatment for a HM patient. PMID- 26803836 TI - Model and Processes of Acceptance and Commitment Therapy (ACT) for Chronic Pain Including a Closer Look at the Self. AB - Acceptance and commitment therapy (ACT) is one of the so called "third-wave" cognitive behavioral therapies. It has been increasingly applied to chronic pain, and there is accumulating evidence to support its effectiveness. ACT is based on a model of general human functioning called the psychological flexibility (PF) model. Most facets of the PF model have been examined in chronic pain. However, a potential key facet related to "self" appears underappreciated. Indeed, a positive or healthy sense of self seems essential to our well-being, and there have been numerous studies of the self in chronic pain. At the same time, these studies are not currently well organized or easy to summarize. This lack of clarity and integration creates barriers to progress in this area of research. PF with its explicit inclusion of self-related therapeutic processes within a broad, integrative, theoretical model may help. The current review summarizes the PF model in the context of chronic pain with a specific emphasis on the parts of the model that address self-related processes. PMID- 26803837 TI - Inhibition of DNA-Topoisomerase I by Acylated Triterpene Saponins from Pittosporum angustifolium Lodd. AB - Previous phytochemical investigation of the leaves and seeds of Pittosporum angustifolium Lodd. led to the isolation and structural elucidation of polyphenols and triterpene saponins. Evaluation for cytotoxicity of isolated saponins revealed that the predominant structural feature for a cytotoxic activity are acyl substituents at the oleanane aglycon backbone. The present work reports the results of a screening of 10 selected acylated saponins for their potential to inhibit the human DNA-topoisomerase I, giving rise to IC50 values in a range of 2.8-46.5 uM. To clarify the mode of observed cytotoxic action and, moreover, to distinguish from a pure surfactant effect which is commonly accompanied with saponins, these results indicate an involvement of the topoisomerase I and its role as a possible target structure for a cytotoxic activity. In addition, computational predictions of the fitting of saponins to the topoisomerase I-DNA complex, indicate a similar binding mode to that of clinically used topoisomerase I inhibitors. Ten acylated triterpene saponins from Pittosporum angustifolium were investigated for their potential to inhibit the human DNA-topoisomerase I and computational predictions of the fitting of saponins to the topoisomerase I-DNA complex were carried out. PMID- 26803838 TI - Tolerability and persistence in a large, prospective case series of women prescribed mirabegron. AB - INTRODUCTION AND HYPOTHESIS: Most published data on mirabegron relates to short term clinical trials and suggest that it might be effective in controlling OAB and have low side effects. This study aimed to identify persistence with mirabegron, changes in symptoms and quality of life, and predictors of perseverance over 1 year. METHODS: The study was a large, prospective case series of 354 patients who were prescribed mirabegron for OAB between February 2013 and July 2014. At 1 year, patients filled out patient global impression of improvement, the International Consultation on Incontinence female lower urinary tract symptoms questionnaire (ICIQ-FLUTS) and PFDI questionnaires. The reasons for discontinuing treatment were identified. RESULTS: Outcomes were available for 88 % of the cohort. Twenty five percent continued mirabegron therapy at 1 year with 26 % "very much better" and 37 % "much better". ICIQ-FLUTS (17.2-13.4; p = 0.002) and urinary distress inventory (UDI) (59.2-44.3; p < 0.001) scores demonstrated significant improvements from baseline (pre-treatment) compared with 1 year. The ICIQ-FLUTS "filling score" increased from 3.55 at 6 weeks to 5.27 at 1 year (p = 0.02) despite continuing mirabegron therapy. The most common causes of discontinuation were lack of efficacy (26 %) and side effects (10 %). Thirty seven percent of the cohort was taking mirabegron in combination with an anticholinergic. Patients who were treatment naive were more likely to discontinue mirabegron than those who had previously taken anticholinergics (p = 0.02). CONCLUSIONS: Over two thirds of patients discontinue mirabegron therapy within 1 year. A significant proportion of patients were on combined therapy to control symptoms. The initial improvement in symptom scores seems to deteriorate. The improvements in quality of life are sustained in patients who persist with therapy. PMID- 26803839 TI - Development of national capabilities in low and middle income countries for research in child mental health. PMID- 26803840 TI - Community Characteristics Associated With Seeking Medical Evaluation for Suspected Child Sexual Abuse in Greater Houston. AB - Child sexual abuse (CSA) affects over 62,000 children annually in the United States. A primary obstacle to the success of a public health prevention strategy is the lack of knowledge around community level risk factors for CSA. We evaluated community level characteristics for children seeking care for suspected CSA in the Greater Houston area for 2009. There was a total incidence rate of medical evaluations for suspected CSA of 5.9/1000 children. We abstracted the medical charts of 1982 (86 %) children who sought a medical evaluation for suspected CSA at three main medical systems in the Greater Houston area for 2009. We evaluated 18 community level variables from the American Community Survey for the 396 zip codes these children lived in. The mean number of cases per Greater Houston zip code was 2.77 (range 0-27), with 62 % of zip codes not having a case at any of the three sites surveyed. Zip codes with a higher than Houston average rate of vacant houses, never married females and unemployed labor force with high family poverty rate, were associated with an increased rate of children seeking care for suspected CSA. We demonstrated zip codes level characteristics which were associated with an increased rate of children seeking care for suspected CSA. Our modelling process and our data have implications for community based strategies aimed at improved surveillance or prevention of CSA. The process of identifying locally specific community level factors suggests target areas which have particular socioeconomic characteristics which are associated with increased rate of seeking CSA evaluations. PMID- 26803841 TI - The need of a new and more physiological preclinical model for Parkinson's disease. PMID- 26803843 TI - Early Childhood Sleep Patterns and Cognitive Development at Age 6 Years: The Generation R Study. AB - Objective: To explore the association of sleep duration and awakening frequency with cognitive outcomes in young children. Methods: Mothers of 2,800 children from the Generation R cohort reported sleep duration and awakenings at children's age 24 months. At age 6 years, validated Dutch measures were used to assess children's nonverbal intelligence and language comprehension. Results: We found a nonlinear association of total sleep time at 24 months with nonverbal intelligence ( p = 0.03) and language comprehension ( p = 0.04) at 6 years. Toddlers sleeping within the recommended 11-14 hr had more favorable cognitive development compared with both extremes. Frequent awakenings were negatively associated with nonverbal intelligence, but not with verbal comprehension. Conclusion: Sleep duration in toddlerhood has an inverted-U-shaped relation with childhood cognitive measures. Frequent awakenings are associated with lower nonverbal intelligence. Given the marked decline in sleep duration and awakenings in toddlerhood, developmental changes of sleep patterns might be important for cognitive development. PMID- 26803845 TI - On Doing the Right Thing. PMID- 26803842 TI - Fast skeletal myofibers of mdx mouse, model of Duchenne muscular dystrophy, express connexin hemichannels that lead to apoptosis. AB - Skeletal muscles of patients with Duchenne muscular dystrophy (DMD) show numerous alterations including inflammation, apoptosis, and necrosis of myofibers. However, the molecular mechanism that explains these changes remains largely unknown. Here, the involvement of hemichannels formed by connexins (Cx HCs) was evaluated in skeletal muscle of mdx mouse model of DMD. Fast myofibers of mdx mice were found to express three connexins (39, 43 and 45) and high sarcolemma permeability, which was absent in myofibers of mdx Cx43(fl/fl)Cx45(fl/fl):Myo-Cre mice (deficient in skeletal muscle Cx43/Cx45 expression). These myofibers did not show elevated basal intracellular free Ca(2+) levels, immunoreactivity to phosphorylated p65 (active NF-kappaB), eNOS and annexin V/active Caspase 3 (marker of apoptosis) but presented dystrophin immunoreactivity. Moreover, muscles of mdx Cx43(fl/fl)Cx45(fl/fl):Myo-Cre mice exhibited partial decrease of necrotic features (big cells and high creatine kinase levels). Accordingly, these muscles showed similar macrophage infiltration as control mdx muscles. Nonetheless, the hanging test performance of mdx Cx43(fl/fl)Cx45(fl/fl):Myo-Cre mice was significantly better than that of control mdx Cx43(fl/fl)Cx45(fl/fl) mice. All three Cxs found in skeletal muscles of mdx mice were also detected in fast myofibers of biopsy specimens from patients with muscular dystrophy. Thus, reduction of Cx expression and/or function of Cx HCs may be potential therapeutic approaches to abrogate myofiber apoptosis in DMD. PMID- 26803846 TI - Criminal Narrative Experience: Relating Emotions to Offence Narrative Roles During Crime Commission. AB - A neglected area of research within criminality has been that of the experience of the offence for the offender. The present study investigates the emotions and narrative roles that are experienced by an offender while committing a broad range of crimes and proposes a model of criminal narrative experience (CNE). Hypotheses were derived from the circumplex of emotions, Frye, narrative theory, and its link with investigative psychology. The analysis was based on 120 cases. Convicted for a variety of crimes, incarcerated criminals were interviewed and the data were subjected to smallest space analysis (SSA). Four themes of CNE were identified: Elated Hero, Calm Professional, Distressed Revenger, and Depressed Victim in line with the recent theoretical framework posited for narrative offence roles. The theoretical implications for understanding crime on the basis of the CNE as well as practical implications are discussed. PMID- 26803844 TI - Pain Psychology: A Global Needs Assessment and National Call to Action. AB - OBJECTIVE: The Institute of Medicine and the draft National Pain Strategy recently called for better training for health care clinicians. This was the first high-level needs assessment for pain psychology services and resources in the United States. DESIGN: Prospective, observational, cross-sectional. METHODS: Brief surveys were administered online to six stakeholder groups (psychologists/therapists, individuals with chronic pain, pain physicians, primary care physicians/physician assistants, nurse practitioners, and the directors of graduate and postgraduate psychology training programs). RESULTS: 1,991 responses were received. Results revealed low confidence and low perceived competency to address physical pain among psychologists/therapists, and high levels of interest and need for pain education. We found broad support for pain psychology across stakeholder groups, and global support for a national initiative to increase pain training and competency in U.S. therapists. Among directors of graduate and postgraduate psychology training programs, we found unanimous interest for a no-cost pain psychology curriculum that could be integrated into existing programs. Primary barriers to pain psychology include lack of a system to identify qualified therapists, paucity of therapists with pain training, limited awareness of the psychological treatment modality, and poor insurance coverage. CONCLUSIONS: This report calls for transformation within psychology predoctoral and postdoctoral education and training and psychology continuing education to include and emphasize pain and pain management. A system for certification is needed to facilitate quality control and appropriate reimbursement. There is a need for systems to facilitate identification and access to practicing psychologists and therapists skilled in the treatment of pain. PMID- 26803879 TI - A study of predictors for identification of risk of complications in patients with liver abscess. AB - BACKGROUND/AIMS: Liver abscess is a significant health problem in developing countries and the complications associated with it are frequently fatal. Hence identification of these complications and anticipating the same will lead to reduction in the mortality and morbidity rate. Such a work will facilitate in identifying patients with risk of complications and will allow for planning of an early intervention. The aim of this study was to identify the predictors of risk of complications in patients with liver abscess. MATERIALS AND METHODS: The data for this retrospective study was obtained from hospital records and included 100 patients diagnosed to have solitary or multiple liver abscess. Complications were defined and history, lab and radiological findings and course of treatment were observed and analyzed in correlation with occurrence of complications. A predictive scoring system was designed for 15 points by giving two points to the factors with 100% correlation and one point to other factors with strong correlation. The score was applied to a validation cohort of 114 different patients and results were noted. RESULTS: Out of the 100 cases studied 24 cases had complications of and the predictive factors included history of alcoholism (> 10 yrs), INR > 1.7 , TLC > 20000/cc and pleural effusion, while other factors had a varying degree of correlation with complication occurrence. It was observed that the new scoring system was successful in identifying patients at risk of developing complications with 100% sensitivity and 93.75% specificity. CONCLUSION: Management of liver abscess can be clearly defined by dividing patients into categories depending upon a new scoring system described in the study and intervention can be planned. PMID- 26803880 TI - [MODIFICATION OF URINE PROTEOME IN HEALTHY HUMAN DURING 21-DAY BED REST]. AB - Mass spectromy-based proteomics was employed to analyze urine from 8 normal volunteers for a 21-day bedrest study (BR). The analysis included trypsinolysis in solution prior to liquid chromatography and tandem mass spectrometry (LC MS/MS), and spectra processing using the bioinformatics tools. Relying on 221 IPI indices with Score from 24 to 1700, 169 different proteins were identified. Molecular functions, biological processes and cell components as the loci of certain protein functioning were determined with the help of UniProt-GOA. Associative interactions networks were constructed using BiNGO. There were 14 proteins identified that are functional in the cardiovascular system mostly. They were annotated and -dynamics of their occurrence throughout the experiment was considered. Grounding on the biological functions of these proteins, an assumption of eligible activation of different biological processes during BR was made. PMID- 26803881 TI - Medical Devices; Ear, Nose, and Throat Devices; Classification of the Tympanic Membrane Contact Hearing Aid. Final order. AB - The Food and Drug Administration (FDA) is classifying the tympanic membrane contact hearing aid into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the tympanic membrane contact hearing aid's classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. PMID- 26803882 TI - Medicare Program; Explanation of FY 2004 Outlier Fixed-Loss Threshold as Required by Court Rulings. Clarification. AB - In accordance with court rulings in cases that challenge the federal fiscal year (FY) 2004 outlier fixed-loss threshold rulemaking, this document provides further explanation of certain methodological choices made in the FY 2004 fixed-loss threshold determination. PMID- 26803847 TI - Nicotine Directly Induces Endoplasmic Reticulum Stress Response in Rat Placental Trophoblast Giant Cells. AB - Nicotine exposure during pregnancy leads to placental insufficiency impairing both fetal and neonatal development. Previous studies from our laboratory have demonstrated that in rats, nicotine augmented endoplasmic reticulum (ER) stress in association with placental insufficiency; however, the underlying mechanisms remain elusive. Therefore, we sought to investigate the possible direct effect of nicotine on ER stress in Rcho-1 rat placental trophoblast giant (TG) cells during differentiation. Protein and/or mRNA expression of markers involved in ER stress (eg, phosphorylated PERK, eIF2alpha, CHOP, and BiP/GRP78) and TG cell differentiation and function (eg, Pl-1, placental growth factor [Pgf], Hsd11b1, and Hsd11b2) were quantified via Western blot or real-time polymerase chain reaction. Nicotine treatment led to dose-dependent increases in the phosphorylation of PERK[Thr981] and eIF2alpha[Ser51], whereas pretreatment with a nicotinic acetylcholine receptor (nAChR) antagonist (mecamylamine hydrochloride) blocked the induction of PERK phosphorylation, verifying the direct involvement of nicotine and nAChR binding. We next investigated select target genes known to play essential roles in placental TG cell differentiation and function (Pl-1, Pgf, Hsd11b1, and Hsd11b2), and found that nicotine significantly augmented the mRNA levels of Hsd11b1 in a dose-dependent manner. Furthermore, using tauroursodeoxycholic acid, a safe bile acid known to improve protein chaperoning and folding, we were able to prevent nicotine-induced increases in both PERK phosphorylation and Hsd11b1 mRNA levels, revealing a potential novel therapeutic approach to reverse the deleterious effects of nicotine exposure in pregnancy. Collectively, these results implicate that nicotine, acting through its receptor, can directly augment ER stress and impair placental function. PMID- 26803883 TI - Predator-prey interactions between the corallivorous snail Coralliophila abbreviata and the carnivorous deltoid rock snail Thais deltoidea. AB - Coral reefs in the Florida Keys have become highly degraded in recent decades, prompting efforts to reestablish populations of vital reef-accreting corals to restore reef structure and ecological function. However, predation on these corals by the corallivorous gastropod Coralliophila abbreviata has been a substantial and chronic impediment to these restoration efforts. We conducted laboratory experiments to determine whether Thais deltoidea, a carnivorous gastropod that commonly occurs with C. abbreviata, is a predator of C. abbreviata. We demonstrated that T. deltoidea readily preys upon C. abbreviata and preferentially targets smaller individuals, a foraging behavior that may optimize the energy gained due to reduced handling and consumption times. If this trophic relationship proves ecologically relevant, understanding the predator prey dynamics between these species could ultimately aid in the development of a comprehensive coral reef restoration strategy for Florida. PMID- 26803884 TI - ACA Co-Ops Continue To Falter and Drop Out. PMID- 26803885 TI - Commercial insurers saying 'no' to hospitals more often. PMID- 26803886 TI - Expensive New Biologic Helps Children Fight Hypophosphatasia. PMID- 26803888 TI - Big meets even bigger: More consolidation in the offing. PMID- 26803887 TI - Digital Health Technology Adoption Depends On Tech Comfort Level, Willingness to Pay. PMID- 26803889 TI - Sagging sign-ups: Slowing enrollment may mean big trouble for the ACA. PMID- 26803890 TI - Slimming too fast: New rules coming for narrowing networks. PMID- 26803891 TI - Picking up the tab: Out-of-network bills will be a hot issue. PMID- 26803892 TI - The 2016 election season: Democrats to play D while GOP devises a game plan. PMID- 26803893 TI - Cyberthievery: Will health care companies respond in 2016? PMID- 26803895 TI - A CONVERSATION WITH JOHN DRISCOLL, CEO, CARECENTRIX. Post-Acute Care Vendors Allow Plans To Focus on Hospital, Medical Costs. PMID- 26803894 TI - Doing the MACRA-ena: Will the celebrations continue in 2016? PMID- 26803896 TI - Using Alternatives to Opioids In an Acute Care Setting. PMID- 26803897 TI - Health System Selects SNFs To Improve Overall Care. PMID- 26803898 TI - Incremental Hospital Costs Associated With Comorbidities of Prematurity. AB - PURPOSE: Preterm birth (PTB), defined as birth at a gestational age (GA) of less than 37 weeks, is associated with increased hospital costs. Lower GA at birth is negatively correlated with the presence of neonatal comorbidities, further increasing costs. This study evaluated incremental costs associated with comorbidities of PTB following spontaneous labor at 24-36 weeks. DESIGN: Birth records from January 2001 to December 2010 at the Medical University of South Carolina were screened to identify infants born at GA 23-37 weeks after uncomplicated singleton pregnancies and surviving to discharge. METHODOLOGY: Comorbidities of interest and incremental costs were analyzed with a partial least squares (PLS) regression model adjusted for comorbidities and GA. Incremental comorbidity-associated costs, as well as total costs, were estimated for infants of GA 24-36 weeks. RESULTS: A total of 4,292 delivery visit records were analyzed. Use of the PLS regression model eliminated issues of multicollinearity and allowed derivation of stable cost estimates. Incremental costs of comorbidities at a mean GA of 34 weeks ranged from $4,529 to $23,121, and exceeded $9,000 in 6 cases. Incremental costs rangedfrom a high of $41,161 for a GA 24-week infant with a comorbidity of retinopathy of prematurity requiring surgery (ROP4) to $3,683 for a GA 36-week infant with a comorbidity of convulsions. Incremental comorbidity costs are additive, so the costs for infants with multiple comorbidities could easily exceed the high of $41,161 seen with ROP4. CONCLUSIONS: The PLS regression model allowed derivation of stable cost estimates from multivariate and highly collinear data and can be used in future cost analyses. Using this data set, predicted costs of all comorbidities, as well as total costs, negatively correlated with GA at birth. PMID- 26803899 TI - AAMC: Physician shortage less severe than previously projected. PMID- 26803901 TI - Farmers' perceptions of health in the Riverland region of South Australia: 'If it's broke, fix it'. AB - OBJECTIVE: To explore perceptions of health among South Australian farmers. DESIGN: Descriptive qualitative study, using semi-structured interviews. SETTING: Two rural towns in the Riverland region of South Australia. PARTICIPANTS: Fifteen adults involved in farming within the Riverland region of South Australia, from a variety of farming industries; age range 23-70 years old; 53% male, 47% female. MAIN OUTCOME MEASURES: Perceptions and definitions of health. RESULTS: Participants described an ecological understanding of health across individual, farm, and community domains. Participants perceived health as being able to function and complete farm work. Participants reported that farm work helped to maintain fitness, but the multiple stress and hazards associated with farming had a significant influence on health. Participants described how health was influenced by community activities and social support from friends and families. Women were reported to take a lead role in health. CONCLUSIONS: Health providers can frame interventions to resonate with the perceptions of health held by people, shaped and formed by the context of farming. Further research is needed to explore farmers' perceptions of health in different locations, from different industries and from a range of age groups. PMID- 26803902 TI - The risk of kidney stones following bariatric surgery: a systematic review and meta-analysis. AB - BACKGROUND: With rising prevalence of morbid obesity, the number of bariatric surgeries performed each year has been increasing worldwide. The objective of this meta-analysis was to assess the risk of kidney stones following bariatric surgery. METHODS: A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through July 2015. Only studies reporting relative risks, odd ratios or hazard ratios (HRs) to compare risk of kidney stones in patients who underwent bariatric surgery versus no surgery were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Four studies (One randomized controlled trial and three cohort studies) with 11,348 patients were included in analysis to assess the risk of kidney stones following bariatric surgery. The pooled RR of kidney stones in patients undergoing bariatric surgery was 1.22 (95% CI, 0.63-2.35). The type of bariatric surgery subgroup analysis demonstrated an increased risk of kidney stones in patients following Roux-en-Y gastric bypass (RYGB) with the pooled RR of 1.73 (95% CI, 1.30-2.30) and a decreased risk of kidney stones in patients following restrictive procedures including laparoscopic banding or sleeve gastrectomy with the pooled RR of 0.37 (95% CI, 0.16-0.85). CONCLUSIONS: Our meta-analysis demonstrates an association between RYGB and increased risk of kidney stones. Restrictive bariatric surgery, on the other hand, may decrease kidney stone risk. Future study with long-term follow-up data is needed to confirm this potential benefit of restrictive bariatric surgery. PMID- 26803900 TI - Genome-wide DNA methylation profiling in the superior temporal gyrus reveals epigenetic signatures associated with Alzheimer's disease. AB - BACKGROUND: Alzheimer's disease affects ~13% of people in the United States 65 years and older, making it the most common neurodegenerative disorder. Recent work has identified roles for environmental, genetic, and epigenetic factors in Alzheimer's disease risk. METHODS: We performed a genome-wide screen of DNA methylation using the Illumina Infinium HumanMethylation450 platform on bulk tissue samples from the superior temporal gyrus of patients with Alzheimer's disease and non-demented controls. We paired a sliding window approach with multivariate linear regression to characterize Alzheimer's disease-associated differentially methylated regions (DMRs). RESULTS: We identified 479 DMRs exhibiting a strong bias for hypermethylated changes, a subset of which were independently associated with aging. DMR intervals overlapped 475 RefSeq genes enriched for gene ontology categories with relevant roles in neuron function and development, as well as cellular metabolism, and included genes reported in Alzheimer's disease genome-wide and epigenome-wide association studies. DMRs were enriched for brain-specific histone signatures and for binding motifs of transcription factors with roles in the brain and Alzheimer's disease pathology. Notably, hypermethylated DMRs preferentially overlapped poised promoter regions, marked by H3K27me3 and H3K4me3, previously shown to co-localize with aging associated hypermethylation. Finally, the integration of DMR-associated single nucleotide polymorphisms with Alzheimer's disease genome-wide association study risk loci and brain expression quantitative trait loci highlights multiple potential DMRs of interest for further functional analysis. CONCLUSION: We have characterized changes in DNA methylation in the superior temporal gyrus of patients with Alzheimer's disease, highlighting novel loci that facilitate better characterization of pathways and mechanisms underlying Alzheimer's disease pathogenesis, and improve our understanding of epigenetic signatures that may contribute to the development of disease. PMID- 26803903 TI - Continuous adsorption and biotransformation of micropollutants by granular activated carbon-bound laccase in a packed-bed enzyme reactor. AB - Laccase was immobilized on granular activated carbon (GAC) and the resulting GAC bound laccase was used to degrade four micropollutants in a packed-bed column. Compared to the free enzyme, the immobilized laccase showed high residual activities over a broad range of pH and temperature. The GAC-bound laccase efficiently removed four micropollutants, namely, sulfamethoxazole, carbamazepine, diclofenac and bisphenol A, commonly detected in raw wastewater and wastewater-impacted water sources. Mass balance analysis showed that these micropollutants were enzymatically degraded following adsorption onto GAC. Higher degradation efficiency of micropollutants by the immobilized compared to free laccase was possibly due to better electron transfer between laccase and substrate molecules once they have adsorbed onto the GAC surface. Results here highlight the complementary effects of adsorption and enzymatic degradation on micropollutant removal by GAC-bound laccase. Indeed laccase-immobilized GAC outperformed regular GAC during continuous operation of packed-bed columns over two months (a throughput of 12,000 bed volumes). PMID- 26803904 TI - Strain improvement of Chlorella sp. for phenol biodegradation by adaptive laboratory evolution. AB - Microalgae are highly efficient photosynthesis cell factories for CO2 capture, biofuel productions and wastewater treatment. Phenol is a typical environmental contaminant. Microalgae normally have a low tolerance for, and a low degradation rate to, high concentration of phenol. Adaptive laboratory evolution was performed for phenolic wastewater treatment by Chlorella sp. The resulting strain was obtained after 31 cycles (about 95d) under 500mg/L phenol as environmental stress. It could grow under 500mg/L and 700mg/L phenol without significant inhibition. The maximal biomass concentrations of the resulting strain at day 8 were 3.40g/L under 500mg/L phenol and 2.70g/L under 700mg/L phenol, respectively. They were more than two times of those of the original strain. In addition, 500mg/L phenol was fully removed by the resulting strain in 7d when the initial cell density was 0.6g/L. PMID- 26803905 TI - The rapid identification of elution conditions for therapeutic antibodies from cation-exchange chromatography resins using high-throughput screening. AB - Cation-exchange chromatography is widely used in the purification of therapeutic antibodies, wherein parameters such as elution pH and counterion concentration require optimization for individual antibodies across different chromatography resins. With a growing number of antibodies in clinical trials and the pressure to expedite process development, we developed and automated a high-throughput batch-binding screen to more efficiently optimize elution conditions for cation exchange chromatography resins. The screen maps the binding behavior of antibodies and impurities as a function of pH and counterion concentration in terms of a partition coefficient (Kp). Using this approach, the binding behavior of a library of antibodies was assessed on Poros 50HS and SP Sepharose Fast Flow resins. The diversity in binding behavior between antibodies and across resins translated to the requirement of a variable counterion concentration to elute each antibody. This requirement can be met through the use of a gradient elution. However, a gradient of increasing counterion concentration spans the transition from binding to non-binding for impurities as well as the antibody, resulting in the elution of impurities within the antibody elution peak. Step elution conditions that selectively elute the antibody while retaining impurities on the resin can now be rapidly identified using our high-throughput approach. We demonstrate that by correlating antibody Kp to elution pool volume and yield on packed-bed columns and through the calculation of a separation factor, we can efficiently optimize step elution conditions that maximize impurity clearance and yield for each antibody. PMID- 26803906 TI - Quantitative enantioseparation of amino acids by comprehensive two-dimensional gas chromatography applied to non-terrestrial samples. AB - This work presents an improved analytical procedure for the resolution and quantification of amino acid enantiomers by multidimensional gas chromatography. The procedure contains a derivatization step, by which amino acids were transformed into N(O,S)-ethoxycarbonylheptafluorobutyl esters. It was optimized for the resolution of non-proteinogenic amino acids in the matrix of complex non terrestrial samples. The procedure has proven to be highly sensitive and shows a wide linearity range with 0.005-3 pmol detection limits for quantitative determinations. The developed procedure was tested on a sample of the Murchison meteorite, for which obtained chromatograms show excellent peak resolution, minimal co-elution and peak overlap. We conclude that comprehensive two dimensional chromatography, in combination with the optimized derivatization method is a highly suitable technique for the analysis of samples with very limited quantities and containing potentially prebiotic molecules, such as interstellar ice analogs and meteorites. PMID- 26803907 TI - Review of analytical methods for the determination of pesticide residues in grapes. AB - This review presents an overview of analytical methods for the analysis of pesticide residues in grapes and by-products in the last decade. The most widely used detection technique for the determination of pesticides in grapes is mass spectrometry combined with gas and/or liquid chromatography. In general, multi residue methods with selective sample treatment methodologies have been developed for this purpose. However, this review focuses not only on these common multi residue methods but also on specific methodologies as single-residue methods for the analysis of pesticides in grapes and by-products. Finally, the limitations of multi-residue methods, the future perspectives and the trends for pesticide residue analysis in grapes are reviewed. PMID- 26803908 TI - Using Marginal Structural Modeling to Estimate the Cumulative Impact of an Unconditional Tax Credit on Self-Rated Health. AB - In previous studies, researchers estimated short-term relationships between financial credits and health outcomes using conventional regression analyses, but they did not account for time-varying confounders affected by prior treatment (CAPTs) or the credits' cumulative impacts over time. In this study, we examined the association between total number of years of receiving New Zealand's Family Tax Credit (FTC) and self-rated health (SRH) in 6,900 working-age parents using 7 waves of New Zealand longitudinal data (2002-2009). We conducted conventional linear regression analyses, both unadjusted and adjusted for time-invariant and time-varying confounders measured at baseline, and fitted marginal structural models (MSMs) that more fully adjusted for confounders, including CAPTs. Of all participants, 5.1%-6.8% received the FTC for 1-3 years and 1.8%-3.6% for 4-7 years. In unadjusted and adjusted conventional regression analyses, each additional year of receiving the FTC was associated with 0.033 (95% confidence interval (CI): -0.047, -0.019) and 0.026 (95% CI: -0.041, -0.010) units worse SRH (on a 5-unit scale). In the MSMs, the average causal treatment effect also reflected a small decrease in SRH (unstabilized weights: beta = -0.039 unit, 95% CI: -0.058, -0.020; stabilized weights: beta = -0.031 unit, 95% CI: -0.050, 0.007). Cumulatively receiving the FTC marginally reduced SRH. Conventional regression analyses and MSMs produced similar estimates, suggesting little bias from CAPTs. PMID- 26803911 TI - Experimental Observation of Bohr's Nonlinear Fluidic Surface Oscillation. AB - Niels Bohr in the early stage of his career developed a nonlinear theory of fluidic surface oscillation in order to study surface tension of liquids. His theory includes the nonlinear interaction between multipolar surface oscillation modes, surpassing the linear theory of Rayleigh and Lamb. It predicts a specific normalized magnitude of 0.416eta(2) for an octapolar component, nonlinearly induced by a quadrupolar one with a magnitude of eta much less than unity. No experimental confirmation on this prediction has been reported. Nonetheless, accurate determination of multipolar components is important as in optical fiber spinning, film blowing and recently in optofluidic microcavities for ray and wave chaos studies and photonics applications. Here, we report experimental verification of his theory. By using optical forward diffraction, we measured the cross-sectional boundary profiles at extreme positions of a surface-oscillating liquid column ejected from a deformed microscopic orifice. We obtained a coefficient of 0.42 +/- 0.08 consistently under various experimental conditions. We also measured the resonance mode spectrum of a two-dimensional cavity formed by the cross-sectional segment of the liquid jet. The observed spectra agree well with wave calculations assuming a coefficient of 0.414 +/- 0.011. Our measurements establish the first experimental observation of Bohr's hydrodynamic theory. PMID- 26803912 TI - Changes in the components and biotoxicity of dissolved organic matter in a municipal wastewater reclamation reverse osmosis system. AB - The characteristics of dissolved organic matter (DOM) and the biotoxicity of these components were investigated in a municipal wastewater reclamation reverse osmosis (mWRRO) system with a microfiltration (MF) pretreatment unit. The MF pretreatment step had little effect on the levels of dissolved organic carbon (DOC) in the secondary effluent, but the addition of chlorine before MF promoted the formation of organics with anti-estrogenic activity. The distribution of excitation emission matrix (EEM) fluorescence constituents exhibited obvious discrepancies between the secondary effluent and the reverse osmosis (RO) concentrate. Using size exclusion chromatography, DOM with low molecular weights of approximately 1.2 and 0.98 kDa was newly formed during the mWRRO. The normalized genotoxicity and anti-estrogenic activity of the RO concentrate were 32.1 +/- 10.2 MUg4-NQO/mgDOC and 0.36 +/- 0.08 mgTAM/mgDOC, respectively, and these values were clearly higher than those of the secondary effluent and MF permeate. The florescence volume of Regions I and II in the EEM spectrum could be suggested as a surrogate for assessing the genotoxicity and anti-estrogenic activity of the RO concentrate. PMID- 26803913 TI - Rationale and Design of the PROSPECTIVE Trial: Probucol Trial for Secondary Prevention of Atherosclerotic Events in Patients with Prior Coronary Heart Disease. AB - BACKGROUND: Reduction of serum LDL-cholesterol by statins was shown to improve clinical outcomes in patients with coronary heart disease (CHD). Although intensive statin therapy significantly reduced cardiovascular risks, atherosclerotic cardiovascular events have not been completely prevented. Therefore, effective pharmacologic therapy is necessary to improve "residual risks" in combination with statins. Probucol has a potent antioxidative effect, inhibits the oxidation of LDL, and reduces xanthomas. Probucol Trial for Secondary Prevention of Atherosclerotic Events in Patients with Prior Coronary Heart Disease (PROSPECTIVE) is a multicenter, randomized, prospective study designed to test the hypothesis that the addition of probucol to other lipid lowering drugs will prevent cerebro- and cardiovascular events in patients with prior coronary events and high LDL cholesterol levels. STUDY DESIGN: The study will recruit approximately 860 patients with a prior CHD and dyslipidemia with LDL-C level >=140 mg/dl without any medication and those treated with any lipid lowering drugs with LDL-C level >=100 mg/dl. Lipid-lowering agents are continuously administered during the study period in control group, and probucol (500 mg/day, 250 mg twice daily) is added to lipid-lowering therapy in the test group. The efficacy and safety of probucol with regard to the prevention of cerebro- and cardiovascular events and the intima-media thickness of carotid arteries as a surrogate marker will be evaluated. SUMMARY: PROSPECTIVE will determine whether the addition of probucol to other lipid-lowering drugs improves cerebro- and cardiovascular outcomes in patients with prior coronary heart disease. Furthermore, the safety of a long-term treatment with probucol will be clarified. PMID- 26803915 TI - Foley Catheter-Assisted Laparoscopic Treatment of Type II Cesarean Scar Pregnancy. AB - Cesarean scar pregnancy (CSP) is an ectopic pregnancy in which the zygote implants in the scar of a previous cesarean section. In type II CSP the zygote implants more deeply. We report a retrospective case series of 8 patients who underwent laparoscopic surgery with the aid of a Foley catheter deployed in the lower uterine segment under ultrasound guidance at the beginning of the surgery. This approach facilitates locating, identifying, and removing the lesion. It also may reduce bleeding via wound compression. PMID- 26803916 TI - Management of Cesarean Scar Pregnancy Using Ultrasound-Guided Dilation and Curettage. AB - STUDY OBJECTIVE: To evaluate the potential risk factors associated with failed ultrasound-guided dilation and curettage (D&C) treatment of cesarean scar pregnancy (CSP). DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Fifty-one patients diagnosed with CSP and treated with ultrasound guided D&C at Shanghai General Hospital of Shanghai Jiao Tong University. INTERVENTION: Lesion resection using ultrasound-guided D&C. MEASUREMENTS AND MAIN RESULTS: Clinical characteristics, vaginal bleeding, abdominal pain, the size of the gestational sac, cardiac motion, blood flow around the gestational sac, cesarean scar thickness, and serum beta-human chorionic gonadotropin (beta-hCG) levels were compared between the successful operation group and the failed operation group. Cesarean scar thickness was the main risk factor that determined the success of ultrasound-guided D&C. The success rates were 50% and 97.67% for those with cesarean scars <3 mm thick and those with scars >3 mm thick, respectively (p = .001). The success rate was also associated with the abundance of blood flow surrounding the capsule and size of the gestational sac (p < .005). Surgical success was not affected by abnormal vaginal bleeding, abdominal pain, cardiac motion, or serum beta-hCG levels. CONCLUSION: Ultrasound-guided D&C is the first choice for treating CSP if the cesarean scar is >3 mm thick, blood flow is not abundant, and the maximum diameter of the gestational sac is <30 mm. A transabdominal procedure is preferred for patients with high-risk factors. PMID- 26803917 TI - In Response to "The Importance of Transparency in Data Reporting". PMID- 26803918 TI - Hysteroscopic Patterns in Women on Treatment With Ulipristal Acetate 5 mg/day: A Preliminary Study. AB - STUDY OBJECTIVE: To describe the hysteroscopic findings in women on treatment with ulipristal acetate (UPA) and to define the most common hysteroscopic patterns related to the treatment and compare them with the histologic findings. DESIGN: Preliminary study. SETTING: OB-GYN and Gynecology Oncology Clinic, Military Medical Institute, Ministry of Defense, Warsaw, Poland, and Obstetrics and Gynecology Department, University of Bari, Italy. PATIENTS: Seventy-four premenopausal patients complaining of abnormal uterine bleeding due to uterine myomas and on treatment with UPA 5 mg/day for at least 30 days. INTERVENTIONS: Women received transvaginal sonography (TVS) and then office hysteroscopy and visually guided endometrial biopsies. Video hysteroscopies were recorded in digital format. Pictures were evaluated by 2 authors off-line and compared with histologic results. MEASUREMENTS AND MAIN RESULTS: Hysteroscopic aspects and classification of progesterone receptor modulator-associated endometrial changes were measured. The most common hysteroscopic finding was the combination of a flat subtle epithelium with small glandular openings; large isolated or confluent cysts in the stroma, giving the surface a floating aspect at fluid distention; and well-evident subendometrial vascular network with a "chicken-wire" vascular pattern (44.6%). This finding accounted for 82% of cases with endometrial thickness > 10 mm at TVS. Histology confirmed a combination of epithelial secretory (vacuoles) and hypotrophic effects (small and dilated glands), whereas at stromal level the combination of cysts, dense stroma, and vascular wall thickening was found. At 3 months follow-up echographic, hysteroscopic, and histologic endometrial patterns were normal in all patients. CONCLUSIONS: In most women on UPA and with thickened endometrium at TVS, the hysteroscopy showed benign and characteristics aspects related to the ambivalent effects of UPA on progesterone receptor. These alterations took place just after 1 month of treatment but disappeared within 3 months of stopping treatment. PMID- 26803919 TI - A Prospective Analysis of Hysteroscopic Morcellation in the Management of Intrauterine Pathologies. AB - OBJECTIVE: To determine the effectiveness of the MyoSure intrauterine mechanical morcellator device for removal of intrauterine pathology. DESIGN: Prospective cohort study (Canadian Task Force classification II-2). INTERVENTION: This study was performed at the Royal Hospital for Women and Prince of Wales Private Hospital, Sydney, Australia. All women undergoing hysteroscopic removal of intrauterine pathology using the MyoSure device between January 2013 and June 2015 were included. RESULTS: A total of 255 MyoSure procedures were performed, with 61% performed by trainees. Resection of leiomyomas occurred in 40% or cases, polyps in 39%, combination pathology in 9%, pregnancy products in 6%, and preinvasive or invasive disease in 5% of cases. Complete resection of pathology was achieved in 92% of polyps, 66% of leiomyomas, and 87% of pregnancy tissue. Leiomyomas were more likely to be completely resected when surgery was performed by an attending physician or senior resident, however there was no statistically significant difference in clinical outcomes. When leiomyomas were stratified according to size, 87% of leiomyomas <=40 mm were completely resected with only 48% of leiomyomas >40 mm completely resected with the index surgery. No intraoperative complications occurred. Postoperative outcomes included symptom resolution in 76%, further surgery (repeat hysteroscopy or hysterectomy) in 10%, pregnancy in 2%, and medical/conservative management in 12% of patients. CONCLUSION: The MyoSure device is very effective when used to resect endometrial polyps. Leiomyomas >40 mm are unlikely to be completely resected at a single operation when using the MyoSure device. Similar clinical outcomes were obtained when procedures were performed by trainees compared to senior clinicians. PMID- 26803920 TI - The True Educational Tool. PMID- 26803921 TI - Specific cognitive-neurophysiological processes predict impulsivity in the childhood attention-deficit/hyperactivity disorder combined subtype. AB - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatric disorders in childhood. Besides inattention and hyperactivity, impulsivity is the third core symptom leading to diverse and serious problems. However, the neuronal mechanisms underlying impulsivity in ADHD are still not fully understood. This is all the more the case when patients with the ADHD combined subtype (ADHD-C) are considered who are characterized by both symptoms of inattention and hyperactivity/impulsivity. METHOD: Combining high density electroencephalography (EEG) recordings with source localization analyses, we examined what information processing stages are dysfunctional in ADHD-C (n = 20) compared with controls (n = 18). RESULTS: Patients with ADHD-C made more impulsive errors in a Go/No-go task than healthy controls. Neurophysiologically, different subprocesses from perceptual gating to attentional selection, resource allocation and response selection processes are altered in this patient group. Perceptual gating, stimulus-driven attention selection and resource allocation processes were more pronounced in ADHD-C, are related to activation differences in parieto-occipital networks and suggest attentional filtering deficits. However, only response selection processes, associated with medial prefrontal networks, predicted impulsive errors in ADHD-C. CONCLUSIONS: Although the clinical picture of ADHD-C is complex and a multitude of processing steps are altered, only a subset of processes seems to directly modulate impulsive behaviour. The present findings improve the understanding of mechanisms underlying impulsivity in patients with ADHD-C and might help to refine treatment algorithms focusing on impulsivity. PMID- 26803922 TI - Identification of Factors that Predict whether the Right Parasternal View Is Required for Accurate Evaluation of Aortic Stenosis Severity. AB - BACKGROUND: To accurately assess aortic stenosis (AS) severity, multiple windows should be used to best align the Doppler beam with the flow direction of the stenotic jet. To evaluate: (1) the frequency at which the highest peak AV velocity is found in the right parasternal window (RPW), (2) the extent of correlation between aortic root angulation and the location of the highest peak AV jet velocity, and (3) which patients would benefit most from RPW-based assessment of AS severity. METHODS: We evaluated AS velocity in the apical window (AW) and RPW by continuous-wave Doppler (CWD) in 263 patients with more than moderate AS. If the AV was inaccessible by the left parasternal long-axis view, the aortoseptal angle was measured by echocardiography and a sagittal view of a computed tomography (CT). RESULTS: Patients were divided into two groups, the RPW group and the AW group. Significant differences were observed between the two groups regarding the sinus of Valsalva diameter, the aortoseptal angle as measured by echocardiography, and the type of valve. The aortoseptal angle as measured by echocardiography was larger in the AW group compared with the RPW group. Aortoseptal angle (P < 0.001) and valve type (P = 0.036) were independent predictors that the highest AV Vmax would be obtained from the RPW. CONCLUSIONS: The right parasternal window must be evaluated to achieve the most accurate assessment of AS severity, especially in patients with an aortoseptal angle <119 degrees in the parasternal long-axis view as measured by echocardiography. PMID- 26803923 TI - A window to beyond the orbit: the value of optical coherence tomography in non ocular disease. AB - Optical coherence tomography (OCT) imaging of the eye has become an essential tool for the ophthalmologist, aiding diagnosis and assisting with treatment decisions, in many ocular diseases. However, there is an evolving role for OCT in informing on non-ocular diseases, which ophthalmologists should be aware of. The purpose of this review was to examine recent evidence for the role of ocular OCT imaging to evaluate disease beyond the orbit and to discuss possible opportunities and challenges arising from this, from the perspective of the ophthalmologist. PMID- 26803924 TI - Direct conversion of xylan to butanol by a wild-type Clostridium species strain G117. AB - Lignocellulosic biomass has great potential for use as a carbon source for the production of second-generation biofuels by solventogenic bacteria. Here we describe the production of butanol by a newly discovered wild-type Clostridium species strain G117 with xylan as the sole carbon source for fermentation. Strain G117 produced 0.86 +/- 0.07 g/L butanol and 53.4 +/- 0.05 mL hydrogen directly from 60 g/L xylan provided that had undergone no prior enzymatic hydrolysis. After process optimization, the amount of butanol produced from xylan was increased to 1.24 +/- 0.37 g/L. In contrast to traditional acetone-butanol ethanol (ABE) solventogenic fermentation, xylan supported fermentation in strain G117 and negligible amount of acetone was produced. The expression of genes normally associated with acetone production (adc and ctfB2) were down-regulated compared to xylose fed cultures. This lack of acetone production may greatly simplify downstream separation process. Moreover, higher amount of butanol (2.94 g/L) was produced from 16.99 g/L xylo-oligosaccharides, suggesting a major role for strain G117 in butanol production from xylan and its oligosaccharides. The unique ability of strain G117 to produce a considerable amount of butanol directly from xylan without producing undesirable fermentation byproducts opens the door to the possibility of cost-effective biofuels production in a single step. Biotechnol. Bioeng. 2016;113: 1702-1710. (c) 2016 Wiley Periodicals, Inc. PMID- 26803927 TI - Determination of Nonanthocyanin Phenolic Compounds Using High-Resolution Mass Spectrometry (UHPLC-Orbitrap-MS/MS) and Impact of Storage Conditions in a Beverage Made from Strawberry by Fermentation. AB - Overproduction of strawberry leads to food waste, as it is very perishable. Therefore, strategies to transform it into new products are appreciated. This research focuses on characterization of the nonanthocyanin phenolic content of a beverage obtained from strawberry by gluconic and acetic fermentation and subsequently monitored for 90 days of storage, at two temperatures. Sixty-four nonanthocyanin (poly)phenols were identified by high-resolution mass spectrometry (UHPLC coupled with linear trap quadrupole and Orbitrap mass analyzer) and, for the first time, four compounds were reported in beverages fermented from strawberry: aromadendrin hexoside, phloretin 2'-O-xylosyl glucoside, dihydroferulic acid 4-O-glucuronide, and kaempferol hexosyl hexoside. During the storage time the increase in protocatechuic acid content was 13 times and condensed tannins diminished, especially procyanidin trimer. Statistical analysis showed that the composition remains unchanged until day 15 of storage at room temperature (27-30 degrees C) and until day 30 under refrigerated conditions (4 degrees C). PMID- 26803928 TI - Intolerance of uncertainty as a predictor of post-traumatic stress symptoms following a traumatic event. AB - Intolerance of uncertainty (IU) has been associated with elevated post-traumatic stress symptoms (PTSS) in the extant literature. However, no research to date has investigated whether pre-trauma IU predicts PTSS following trauma exposure. The current study prospectively examined the relationship between IU and PTSS within a sample of individuals with various levels of exposure to a university campus shooting. We hypothesized that pre-trauma IU would predict elevated PTSS following a campus shooting, even after covarying for anxiety sensitivity (AS), a known correlate of PTSS. Participants included undergraduates (n=77) who completed a self-report battery in Introductory Psychology. After a campus shooting, they were invited to complete measures of PTSD symptoms and level of exposure to the shooting. As anticipated, results revealed pre-trauma IU as a significant predictor of elevated PTSS following the campus shooting. These results remained significant after covarying for pre-trauma levels of AS. Our results are the first to demonstrate that elevated pre-trauma levels of IU predict later PTSS following exposure to a traumatic event. This finding is discussed in terms of promising directions for future research and treatment strategies. PMID- 26803929 TI - Autologous distal clavicle versus autologous coracoid bone grafts for restoration of anterior-inferior glenoid bone loss: a biomechanical comparison. AB - BACKGROUND: Treating anterior glenoid bone loss in patients with recurrent shoulder instability is challenging. Coracoid transfer techniques are associated with neurologic complications and neuroanatomic alterations. The purpose of our study was to compare the contact area and pressures of a distal clavicle autograft with a coracoid bone graft for the restoration of anterior glenoid bone loss. We hypothesized that a distal clavicle autograft would be as effective as a coracoid graft. METHODS: In 13 fresh-frozen cadaveric shoulder specimens, we harvested the distal 1.0 cm of each clavicle and the coracoid bone resection required for a Latarjet procedure. A compressive load of 440 N was applied across the glenohumeral joint at 30 degrees and 60 degrees of abduction, as well as 60 degrees of abduction with 90 degrees of external rotation. Pressure-sensitive film was used to determine normal glenohumeral contact area and pressures. In each specimen, we created a vertical, 25% anterior bone defect, reconstructed with distal clavicle (articular surface and undersurface) and coracoid bone grafts, and determined the glenohumeral contact area and pressures. We used analysis of variance for group comparisons and a Tukey post hoc test for individual comparisons (with P <.05 indicating a significant difference). RESULTS: The articular distal clavicle bone graft provided the lowest mean pressure in all testing positions. The coracoid bone graft provided the greatest contact area in all humeral positions, but the difference was not significant. CONCLUSION: An articular distal clavicle bone graft is comparable in glenohumeral contact area and pressures to an optimally placed coracoid bone graft for restoring glenoid bone loss. LEVEL OF EVIDENCE: Basic Science Study; Biomechanics. PMID- 26803930 TI - Three-dimensional shoulder kinematics normalize after rotator cuff repair. AB - BACKGROUND: Patients with a rotator cuff (RC) tear often exhibit scapular dyskinesia with increased scapular lateral rotation and decreased glenohumeral elevation with arm abduction. We hypothesized that in patients with an RC tear, scapular lateral rotation, and thus glenohumeral elevation, will be restored to normal after RC repair. METHODS: Shoulder kinematics were quantitatively analyzed in 26 patients with an electromagnetic tracking device (Flock of Birds) before and 1 year after RC repair in this observational case series. We focused on humeral range of motion and scapular kinematics during abduction. The asymptomatic contralateral shoulder was used as the control. Changes in scapular kinematics were associated with the gain in range of motion. Shoulder kinematics were analyzed using a linear mixed model. RESULTS: Mean arm abduction and forward flexion improved after surgery by 20 degrees (95% confidence interval [CI], 2.7 degrees -36.5 degrees ; P = .025) and 13 degrees (95% CI, 1.2 degrees -36.5 degrees ; P = .044), respectively. Kinematic analyses showed decreases in mean scapular protraction (ie, internal rotation) and lateral rotation (ie, upward rotation) during abduction by 3 degrees (95% CI, 0.0 degrees -5.2 degrees ; P = .046) and 4 degrees (95% CI, 1.6 degrees -8.4 degrees ; P = .042), respectively. Glenohumeral elevation increased by 5 degrees (95% CI, 0.6 degrees -9.7 degrees ; P = .028) at 80 degrees . Humeral range of motion increased when scapular lateral rotation decreased and posterior tilt increased. CONCLUSIONS: Scapular kinematics normalize after RC repair toward a symmetrical scapular motion pattern as observed in the asymptomatic contralateral shoulder. The observed changes in scapular kinematics are associated with an increased overall range of motion and suggest restored function of shoulder muscles. PMID- 26803931 TI - Reverse total shoulder arthroplasty with combined deltoid reconstruction in patients with anterior and/or middle deltoid tears. AB - BACKGROUND AND HYPOTHESIS: Deltoid disruption has traditionally been an absolute contraindication to performing a reverse total shoulder arthroplasty (RTSA), and options available to patients have been limited. We present a series of patients with deltoid tears that underwent concomitant RTSA with deltoid reconstruction. We hypothesize that this combined procedure provides an acceptable, functional alternative for this complex patient population. MATERIALS AND METHODS: We retrospectively identified all patients who were treated by a single surgeon with a concomitant RTSA and deltoid reconstruction from 2004 to 2012 with minimum 24 month follow-up. Six shoulders in 5 patients met these criteria. The mean age was 69 years (range, 61-79 years), and the mean follow-up period was 76.8 months (range, 24-133 months). We compared preoperative and postoperative range of motion and Penn Shoulder Scores, including subscores, using paired t tests. RESULTS: Mean forward elevation and external rotation increased from 48 degrees and 12 degrees , respectively, to 120 degrees and 22 degrees , respectively. Penn scores increased from 45.2 to 77.8 postoperatively (P = .03). The Penn satisfaction subscore, in particular, improved from 1.1 (of 10) to 9.0 (P = .005). There was a low rate of recurrent deltoid failure (1 of 6 shoulders), and there were no infections or revisions. DISCUSSION: Deltoid reconstruction at the same time as RTSA is a viable treatment option as a salvage procedure for patients with deltoid deficiency who otherwise need RTSA for treatment of massive rotator cuff deficiency. In this small series, simultaneous RTSA and deltoid reconstruction resulted in a functional shoulder with a high level of satisfaction and good motion. LEVEL OF EVIDENCE: Level IV; Case Series; Treatment Study. PMID- 26803932 TI - Risk factors predicting revision surgery after medial epicondylectomy for primary cubital tunnel syndrome. AB - BACKGROUND: Medial epicondylectomy (ME) is one of several accepted surgical options for the treatment of cubital tunnel syndrome (CuTS). Although reported outcomes after ME are generally favorable, few data exist regarding which patients are prone to poorer outcomes requiring revision surgery. The goal of this study was to identify risk factors predicting the need for revision surgery after ME for the treatment of CuTS. METHODS: We conducted a retrospective chart review of all patients treated at our institution with ME for CuTS from 2006 through 2011. We identified patients who underwent additional operations for recurrent or persistent ulnar nerve symptoms as the revision cohort. We performed bivariate analysis to determine which variables had a significant influence on the need for revision surgery. We examined qualitative factors associated with revision, including the degree of bony resection performed during the index ME, and intraoperative findings at the time of revision surgery. RESULTS: Revision surgery was required in 13.3% of cases (11 of 83). On bivariate analysis, younger age, associated workers' compensation claims, lesser disease severity, and preoperative opioid use were all significant predictors of the need for revision surgery. Perineural scarring and heterotopic bone formation about the elbow were the 2 most common findings at the time of revision. CONCLUSIONS: For patients with CuTS, the risk of revision surgery after ME is higher in younger patients, patients with less severe disease, patients taking opioid medications preoperatively, and patients with associated workers' compensation claims. LEVEL OF EVIDENCE: Level IV; Case Series; Treatment Study. PMID- 26803933 TI - Does chondrolysis occur after corticosteroid-analgesic injections? An analysis of patients treated for adhesive capsulitis of the shoulder. AB - BACKGROUND: Clinical studies using continuous infusions of local anesthetics and basic science studies that model injections of local anesthetics have shown chondrotoxicity. However, clinical studies do not exist that have assessed for the risk of chondrolysis in nonarthritic joints exposed to single or intermittent corticosteroid or analgesic injections. Currently, there are no data available to guide the clinician on the safety of using these injections in clinical practice. MATERIALS AND METHODS: A retrospective review of patients treated for adhesive capsulitis of the shoulder with at least 1 intra-articular injection of a corticosteroid and anesthetic was performed. The inclusion criteria were a diagnosis of adhesive capsulitis and a minimum 2-year follow-up. Prospective follow-up was performed to obtain patient-determined outcome scores, range of motion, and radiographs to determine the presence of chondrolysis. RESULTS: Fifty six patients with a mean age of 52.5 +/- 7.2 years were enrolled at a mean follow up of 54 months. The mean number of injections performed was 1.5 +/- 0.7 (range, 1-4). At final follow-up, the mean Western Ontario Osteoarthritis of the Shoulder score was 91.4% +/- 14.2%; Disabilities of the Arm, Shoulder and Hand score, 6.7 +/- 9.6; Shoulder Pain and Disability Index score, 7.4 +/- 11.4; and Single Assessment Numeric Evaluation score, 92.7% +/- 10.1%. The Shoulder Activity Score was 8.3 +/- 4.7. Passive and active forward elevation, external rotation, internal rotation, and cross-body adduction showed no significant differences compared with the unaffected contralateral shoulder. There was no radiographic evidence of chondrolysis in any patient. CONCLUSIONS: This study did not show chondrolysis in patients treated with an intra-articular corticosteroid and local anesthetic for adhesive capsulitis. The findings of this study do not support the cessation of using intra-articular analgesic-corticosteroid injections for the treatment of adhesive capsulitis. LEVEL OF EVIDENCE: Level IV; Case Series; Treatment Study. PMID- 26803935 TI - Evaluating the transmission routes of hand, foot, and mouth disease in Guangdong, China. AB - Although it is an enteroviral infectious disease, recent studies suggest that respiratory transmission might play a role in the transmission of hand, foot, and mouth disease (HFMD). We evaluated the transmission modes (respiratory and fecal oral transmission) of HFMD among children using a case-control study in Guangdong, China. Our analyses suggested that fecal-oral transmission might be the principal transmission mode of HFMD among children in the study area, and handwashing habits of the children and their parents should be emphasized to control this infection. PMID- 26803938 TI - A dimethacrylate cross-linker cleavable under thermolysis or alkaline hydrolysis conditions: synthesis, polymerization, and degradation. AB - We develop a new platform based on 2,6-pyridinediethanol diesters for introducing polymer degradability under thermolysis or alkaline hydrolysis conditions, with the latter being rare in polymers. Such labile diesters can be cross-linkers, bifunctional initiators and inimers. We demonstrate the power of this platform through the synthesis of the 2,6-pyridinediethanol dimethacrylate cross-linker, its controlled (co)polymerization, and the thermal and hydrolytic cleavage of its (co)polymers. PMID- 26803939 TI - FDI policy statements point towards the future of the dental profession. PMID- 26803937 TI - Axial stretch-dependent cation entry in dystrophic cardiomyopathy: Involvement of several TRPs channels. AB - In Duchenne muscular dystrophy (DMD), deficiency of the cytoskeletal protein dystrophin leads to well-described defects in skeletal muscle but also to dilated cardiomyopathy (DCM). In cardiac cells, the subsarcolemmal localization of dystrophin is thought to protect the membrane from mechanical stress. The dystrophin deficiency leads to membrane instability and a high stress-induced Ca(2+) influx due to dysregulation of sarcolemmal channels such as stretch activated channels (SACs). In this work divalent cation entry has been explored in isolated ventricular Wild Type (WT) and mdx cardiomyocytes in two different conditions: at rest and during the application of an axial stretch. At rest, our results suggest that activation of TRPV2 channels participates to a constitutive basal cation entry in mdx cardiomyocytes.Using microcarbon fibres technique, an axial stretchwas applied to mimic effects of physiological conditions of ventricular filling and study on cation influx bythe Mn(2+)-quenching techniquedemonstrated a high stretch-dependentcationic influx in dystrophic cells, partially due to SACs. Involvement of TRPs channels in this excessive Ca(2+) influx has been investigated using specific modulators and demonstratedboth sarcolemmal localization and an abnormal activity of TRPV2 channels. In conclusion, TRPV2 channels are demonstrated here to play a key role in cation influx and dysregulation in dystrophin deficient cardiomyocytes, enhanced in stretching conditions. PMID- 26803940 TI - FDI policy statement on dental implants: Adopted by the FDI General Assembly: 24 September 2015, Bangkok, Thailand. PMID- 26803941 TI - FDI policy statement on oral health for healthy ageing: Adopted by the FDI General Assembly: 24 September 2015, Bangkok, Thailand. PMID- 26803942 TI - FDI policy statement on dietary free sugars and dental caries: Adopted by the FDI General Assembly: 24 September 2015, Bangkok, Thailand. PMID- 26803943 TI - FDI policy statement on oral health and quality of life: Adopted by the FDI General Assembly: 24 September 2015, Bangkok, Thailand. PMID- 26803944 TI - FDI policy statement on oral cancer: Adopted by the FDI General Assembly: 24 September 2015, Bangkok, Thailand. PMID- 26803945 TI - FDI policy statement on basic dental education: Adopted by the General Assembly: 24 September 2015, Bangkok, Thailand. PMID- 26803946 TI - FDI policy statement on the supervision of allied dental personnel: Adopted by the General Assembly: 24 September 2015, Bangkok, Thailand. PMID- 26803947 TI - FDI policy statement on the dental laboratory technician: Adopted by the General Assembly: 24 September 2015, Bangkok, Thailand. PMID- 26803948 TI - FDI policy statement on the role of the FDI in dental ethics: Adopted by the General Assembly: 24 September 2015, Bangkok, Thailand. PMID- 26803949 TI - Analysis of colorectal cancer outcomes for the Australian National Bowel Cancer Screening Program. AB - The Australian National Bowel Cancer Screening Program (NBCSP) was introduced in Australia in 2006 with the aim of reducing morbidity and mortality from colorectal cancer. This study looked to evaluate the effectiveness of the NBCSP against this aim. The study linked 2006-2008 NBCSP invitees to colorectal cancer incidence and mortality data and categorized NBCSP invitees diagnosed with colorectal cancer into screen-detected, interval cancer and nonparticipant subgroups. Colorectal cancers in those not invited into the NBCSP were categorized as the never invited group. Proportional hazards and logistic regression were used to compare mortality, summary stage and other characteristics between groups. Of 12,689 people diagnosed with colorectal cancer in 2006-2008, the never invited group (10,080 cases) had a 15% higher risk of colorectal cancer death by 31 December 2011, compared with NBCSP invitees (after correcting for lead-time bias). Of the colorectal cancers with "summary stage at first presentation" data (27% of total), diagnoses in the never invited group had 38% higher odds of being more advanced than those diagnosed in NBCSP invitees (distant cancer 19% vs 11%). NBCSP invitees had less risk of dying from colorectal cancer, and were more likely to have less-advanced colorectal cancers when diagnosed, than noninvitees. PMID- 26803950 TI - Botulinum toxin-A injections vs radiotherapy for drooling in ALS. AB - OBJECTIVES: Botulinum neurotoxin (BoNT) injections in the salivary glands and radiotherapy (RT) on these glands are commonly used to alleviate severe drooling in patients with amyotrophic lateral sclerosis (ALS). This study compares BoNT type A with RT based on patient-rated evaluations. MATERIALS & METHODS: A prospective randomized controlled pilot study to compare RT (n = 10; on the parotid and the posterior part of the submandibular glands) with BoNT-A treatment (n = 10; in the parotid glands only, because of the risk of increasing oropharyngeal weakness) in patients with ALS. The primary outcome was the drooling status (burden of drooling), and our secondary interests were the degree of salivation, global change of drooling after treatment, and level of satisfaction with the treatment and negative experiences. RESULTS: There were no statistically significant between-treatment differences for the drooling status after treatment. Only at twelve weeks more saliva reduction was achieved by RT (P = 0.02). Patients treated with RT also described more transient negative experiences (like pain in mandible) directly after treatment. Subgroup analysis showed that patients with very severe dysphagia (no oral intake) were less satisfied and experienced a lower global change of drooling after treatment. CONCLUSIONS: This pilot study showed no significant difference in the burden of drooling between the treatments. However, with RT more saliva reduction was achieved, including negative experiences directly after treatment, but without the risk of decreasing oropharyngeal function. In addition, patients with very severe dysphagia do not seem to benefit from either treatment. PMID- 26803985 TI - Waveguide Characterization of S-Band Microwave Mantle Cloaks for Dielectric and Conducting Objects. AB - We present the experimental characterization of mantle cloaks designed so as to minimize the electromagnetic scattering of moderately-sized dielectric and conducting cylinders at S-band microwave frequencies. Our experimental setup is based on a parallel-plate waveguide system, which emulates a two-dimensional plane-wave scattering scenario, and allows the collection of near-field maps as well as more quantitative assessments in terms of global scattering observables (e.g., total scattering width). Our results, in fairly good agreement with full wave numerical simulations, provide a further illustration of the mantle- cloak mechanism, including its frequency-sensitivity, and confirm its effectiveness both in restoring the near-field impinging wavefront around the scatterer, and in significantly reducing the overall scattering. PMID- 26803987 TI - Total shoulder arthroplasty for proximal humerus fracture is associated with increased hospital charges despite a shorter length of stay. AB - BACKGROUND: Operation choice is a complex decision in the surgical management of proximal humerus fractures. Recently, there has been an increase in the use of total shoulder arthroplasty (TSA) for complex fracture patterns. HYPOTHESIS: Patients with proximal humerus fractures who receive TSA are more likely to have higher hospital charges and a prolonged length of stay relative to patients receiving hemiarthroplasty (HA), open reduction with internal fixation (ORIF) or closed reduction with internal fixation (CRIF). MATERIALS AND METHODS: A statewide electronic database was used to identify 13,316 hospital admissions from 2000-2011 were a proximal humerus fracture was surgically managed in an effort to determine the effect of operation choice on cost and length of stay. A univariate analysis was preformed to examine overall trends in surgical management. Additionally, a periodic, multivariate logistic regression analysis was used to determine how operation choice affected the odds of a high cost hospital stay or a prolonged length of stay after controlling for age, comorbidity burden, gender, and insurance type. RESULTS: After controlling for confounding factors, patients receiving total shoulder arthroplasty (TSA) were 2.25 times more likely to have high total hospital charges than patients receiving HA and 3.21 times more likely than patients receiving ORIF. Additionally, TSA was found to be a significant negative predictor of prolonged length of stay (pLOS). HA, ORIF and CRIF did not significantly predict pLOS. DISCUSSION: The use of TSA for acute proximal humerus fractures is associated with increased hospital costs despite a shorter length of stay when compared to other operative choices. As reverse total shoulder arthroplasty becomes more popular for treatment of this injury, it is important that functional outcomes be interpreted in the context of relative cost trade-offs. LEVEL OF EVIDENCE: Level IV. PMID- 26803986 TI - HOX genes: Major actors in resistance to selective endocrine response modifiers. AB - Long term treatment with therapies aimed at blocking the estrogen- (ER) or androgen receptor (AR) action often leads to the development of resistance to selective modulators of the estrogen receptor (SERMs) in ERalpha-positive breast cancer, or of the androgen receptor (SARMs) in AR-positive prostate cancer. Many underlying molecular events that confer resistance are known, but a unifying theme is yet to be revealed. Receptor tyrosine kinases (RTKs) such EGFR, ERBB2 and IGF1R are major mediators that can directly alter cellular response to the SERM, tamoxifen, but the mechanisms underlying increased expression of RTKs are not clear. A number of HOX genes and microRNAs and non-coding RNAs residing in the HOX cluster, have been identified as important independent predictors of endocrine resistant breast cancer. Recently, convincing evidence has accumulated that several members belonging to the four different HOX clusters contribute to endocrine therapy resistant breast cancer, but the mechanisms remain obscure. In this article, we have reviewed recent progress in understanding of the functioning of HOX genes and regulation of their expression by hormones. We also discuss, in particular, the contributions of several members of the HOX gene family to endocrine resistant breast cancer. PMID- 26803990 TI - Exposure to sublethal levels of PCB-126 impacts fuel metabolism and swimming performance in rainbow trout. AB - Polychlorinated biphenyls (PCBs) are recognized physiological stressors to fish which over time may impair individual performance and perhaps fitness by inducing changes that could have population-level consequences. PCB-126 (3,3',4,4',5 pentachlorobiphenyl) accumulates in lipids and can subsequently be released into the bloodstream during periods of high activity that involve the mobilization of stored fuels to meet with increasing energy demands. The goal of this study was to determine if a sublethal exposure to PCB-126 altered the content of tissue energy supplies (carbohydrates, proteins, amino acids, triglycerides) and impaired swimming performance as well as oxygen consumption in rainbow trout (Oncorhynchus mykiss). Trout were injected intraperitoneally with a single Low (100MUgkg(-1)) or High (400MUgkg(-1)) dose of PCB-126 then swimming performance and metabolic rates from 1 to 9days post-injection were compared to Control (non dosed) fish. Liver ethoxyresorufin-O-deethylase (EROD) activity was assessed as an indication of PCB-126 intoxication while plasma and white muscle tissue metabolites were analyzed as an index of physiological disturbance. Swimming performance, assessed using two successive modified critical swimming speed (Ucrit) tests, was highest for fish in the High PCB-126 treatment; however, their initial condition factor (K) was also higher, largely due to their greater body mass. Trout in the High and Low PCB-126 treatments exhibited impaired recovery following intense exercise as they swam comparatively poorly when provided a second challenge. PCB-exposed fish exhibited reduced spleen somatic indices as well as muscle glucose and glycogen contents; whereas plasma cortisol and glucose levels were elevated, indicating higher metabolic costs during recovery and muscle restoration. Overall, this research provides insights into the sublethal effects of a toxic organic compound on swimming performance in trout. PMID- 26803989 TI - Insights into the venom composition and evolution of an endoparasitoid wasp by combining proteomic and transcriptomic analyses. AB - Parasitoid wasps are abundant and diverse hymenopteran insects that lay their eggs into the internal body (endoparasitoid) or on the external surface (ectoparasitoid) of their hosts. To make a more conducive environment for the wasps' young, both ecto- and endoparasitoids inject venoms into the host to modulate host immunity, metabolism and development. Endoparasitoids have evolved from ectoparasitoids independently in different hymenopteran lineages. Pteromalus puparum, a pupal endoparasitoid of various butterflies, represents a relatively recent evolution of endoparasitism within pteromalids. Using a combination of transcriptomic and proteomic approaches, we have identified 70 putative venom proteins in P. puparum. Most of them show higher similarity to venom proteins from the related ectoparasitoid Nasonia vitripennis than from other more distantly related endoparasitoids. In addition, 13 venom proteins are similar to venoms of distantly related endoparasitoids but have no detectable venom matches in Nasonia. These venom proteins may have a role in adaptation to endoparasitism. Overall, these results lay the groundwork for more detailed studies of venom function and adaptation to the endoparasitic lifestyle. PMID- 26803991 TI - Hallmarks of hyperthermia in driving the future of clinical hyperthermia as targeted therapy: translation into clinical application. AB - Regional hyperthermia is described as a targeted therapy and the definitions of six hallmarks of hyperthermia are proposed, representing the pleiotropic effect of this therapeutic modality to counteract tumour growth and progression. We recommend the considerations of these hallmarks in the design of clinical trials involving regional hyperthermia as targeted therapy. Randomised clinical studies using loco-regional hyperthermia as an adjuvant to radiotherapy or to chemotherapy for locally advanced tumours demonstrate the benefit of the combination compared to either of the standard treatments alone for tumour response, disease control, and patient survival outcome. These impressive results were obtained from proof-of-concept trials for superficial or deep-seated malignancies in unselected patients. None of these trials was designed as tailored approaches for the treatment of specified targets or to select potentially more sensitive subpopulations of patients using eligibility criteria. Based upon clinical examples of targeted chemotherapy, some guidelines are described for the successful development of targeted therapeutic combinations. We also retrospectively analyse the stepwise process of generating an ongoing new clinical trial using hyperthermia as targeted therapy to evade DNA repair in combination with a DNA damaging anticancer agent to implement this new vision. PMID- 26803992 TI - The prevalence of premature ejaculation in young Turkish men. AB - This study was conducted to investigate the prevalence of premature ejaculation (PE) in young Turkish men and to evaluate PE in a population having good physical and mental health. A total of 1230 healthy university graduates aged between 24 and 30 attending the police academy having no physical or mental problems were included in the study. To identify the presence of PE, the participants were asked to complete the premature ejaculation diagnostic tool (PEDT). The mean ages in the PE and non-PE group were 27.3 and 26.7 respectively. There was no statistically significant difference between the two groups concerning age, body mass index (BMI), smoking status and alcohol consumption (P > 0.05). The PE prevalence was found to be 9.2%. The mean PEDT score was calculated as 6.3. Of the participants, 92 scored 11 and higher (9.2%), 66 scored 9 and 10 (6.6%), and the remaining 842 obtained a score equal to or lower than 8 (84.2%). The lower prevalence of PE in young Turkish men compared to the results of studies in the literature can be attributed to the physical and mental well-being of the participants. This study showed that the prevalence of PE in young men with good physical and mental health is lower than that found in the literature. PMID- 26803993 TI - Late primary transplantation in complex congenital heart disease. AB - Heart transplantation is a viable option for patients with congenital heart disease who manifest heart failure, predominantly post-surgical palliation. We present a case of complex congenital heart disease, where surgical palliation was considered not to be an option. Considerate medical management with close follow up allowed for a nine-yr delay until eventual successful heart transplantation. The case also highlights the natural history over nine yr of the effects of right ventricular outflow tract obstruction on the left ventricular remodeling which is analogous to a PA banding in patients with dilated cardiomyopathy. PMID- 26803996 TI - Urticaria as a Presenting Prodromal Manifestation of Attacks of Hereditary Angioedema. PMID- 26803998 TI - Erratum. PMID- 26803999 TI - Synthetic lethal approaches for assessing combinatorial efficacy of chemotherapeutic drugs. AB - The recent advances in pharmacogenomics have made personalized medicine no longer a pipedream but a precise and powerful way to tailor individualized cancer treatment strategies. Cancer is a devastating disease, and contemporary chemotherapeutic strategies now integrate several agents in the treatment of some types of cancer, with the intent to block more than one target simultaneously. This constitutes the premise of synthetic lethality, an attractive therapeutic strategy already demonstrating clinical success in patients with breast and ovarian cancers. Synthetic lethal combinations offer the potential to also target the hitherto "undruggable" mutations that have challenged the cancer field for decades. However, synthetic lethality in clinical cancer therapy is very much still in its infancy, and selecting the most appropriate combinations-or synthetic lethal pairs-is not always an intuitive process. Here, we review some of the recent progress in identifying synthetic lethal combinations and their potential for therapy and highlight some of the tools through which synthetic lethal pairs are identified. PMID- 26804001 TI - Anti-glycan antibodies halt axon regeneration in a model of Guillain Barre Syndrome axonal neuropathy by inducing microtubule disorganization via RhoA-ROCK dependent inactivation of CRMP-2. AB - Several reports have linked the presence of high titers of anti-Gg Abs with delayed recovery/poor prognosis in GBS. In most cases, failure to recover is associated with halted/deficient axon regeneration. Previous work identified that monoclonal and patient-derived anti-Gg Abs can act as inhibitory factors in an animal model of axon regeneration. Further studies using primary dorsal root ganglion neuron (DRGn) cultures demonstrated that anti-Gg Abs can inhibit neurite outgrowth by targeting gangliosides via activation of the small GTPase RhoA and its associated kinase (ROCK), a signaling pathway common to other established inhibitors of axon regeneration. We aimed to study the molecular basis of the inhibitory effect of anti-Gg abs on neurite outgrowth by dissecting the molecular dynamics of growth cones (GC) cytoskeleton in relation to the spatial-temporal analysis of RhoA activity. We now report that axon growth inhibition in DRGn induced by a well characterized mAb targeting gangliosides GD1a/GT1b involves: i) an early RhoA/ROCK-independent collapse of lamellipodia; ii) a RhoA/ROCK dependent shrinking of filopodia; and iii) alteration of GC microtubule organization/and presumably dynamics via RhoA/ROCK-dependent phosphorylation of CRMP-2 at threonine 555. Our results also show that mAb 1B7 inhibits peripheral axon regeneration in an animal model via phosphorylation/inactivation of CRMP-2 at threonine 555. Overall, our data may help to explain the molecular mechanisms underlying impaired nerve repair in GBS. Future work should define RhoA independent pathway/s and effectors regulating actin cytoskeleton, thus providing an opportunity for the design of a successful therapy to guarantee an efficient target reinnervation. PMID- 26804002 TI - Mural nodule of 10 mm or larger as predictor of malignancy for intraductal papillary mucinous neoplasm of the pancreas: Pathological and radiological evaluations. AB - BACKGROUND: We had previously reported that mural nodule (MN) >=10 mm was optimal predictor of malignancy for intraductal papillary mucinous neoplasm (IPMN). However, little is known about its microscopic findings and imaging detectability. METHODS: Medical records and resected specimens of consecutive patients with IPMNs harboring MN >= 10 mm were reviewed. Imaging detectability was determined on reports basis. Malignant IPMNs (noninvasive + invasive carcinomas) were microscopically classified according to localization of high grade dysplasia (HGD) within MN. RESULTS: Thirty-six patients were included. Imaging detectability of MN >= 10 mm in CT, MRI, US and EUS were 64%, 68%, 89%, and 97%, respectively. Thirty-three (92%) IPMNs were histologically diagnosed as malignant. Thirty percent of malignant IPMNs were classified into "diffuse HGD within MN", 40% into "focal HGD within MN", and 30% into "HGD outside MN", in which HGD was not located within MN but in low papillary epithelia around MN. Overall sensitivity of pancreatic juice cytology was calculated as 58%, and for "diffuse HGD within MN", "focal HGD within MN", and "HGD outside MN" as 80%, 62%, and 30%, respectively (p = 0.0237). Univariate-analysis showed localization of HGD within MN was associated with true positive cytology (OR = 5.33, p = 0.043). CONCLUSIONS: Detectability of MN >= 10 mm is excellent in US and EUS. Although HGD is observed within MN in 70% of malignant IPMNs, HGD is located only in low papillary epithelia around MN in the remaining 30%, in which sensitivity of pancreatic juice cytology is shown to be inadequate. PMID- 26804000 TI - Regulation of the T-type Ca(2+) channel Cav3.2 by hydrogen sulfide: emerging controversies concerning the role of H2 S in nociception. AB - Ion channels represent a large and growing family of target proteins regulated by gasotransmitters such as nitric oxide, carbon monoxide and, as described more recently, hydrogen sulfide. Indeed, many of the biological actions of these gases can be accounted for by their ability to modulate ion channel activity. Here, we report recent evidence that H2 S is a modulator of low voltage-activated T-type Ca(2+) channels, and discriminates between the different subtypes of T-type Ca(2+) channel in that it selectively modulates Cav3.2, whilst Cav3.1 and Cav3.3 are unaffected. At high concentrations, H2 S augments Cav3.2 currents, an observation which has led to the suggestion that H2 S exerts its pro-nociceptive effects via this channel, since Cav3.2 plays a central role in sensory nerve excitability. However, at more physiological concentrations, H2 S is seen to inhibit Cav3.2. This inhibitory action requires the presence of the redox sensitive, extracellular region of the channel which is responsible for tonic metal ion binding and which particularly distinguishes this channel isoform from Cav3.1 and 3.3. Further studies indicate that H2 S may act in a novel manner to alter channel activity by potentiating the zinc sensitivity/affinity of this binding site. This review discusses the different reports of H2 S modulation of T type Ca(2+) channels, and how such varying effects may impact on nociception given the role of this channel in sensory activity. This subject remains controversial, and future studies are required before the impact of T-type Ca(2+) channel modulation by H2 S might be exploited as a novel approach to pain management. PMID- 26804003 TI - Long-term trends in the incidence and relative survival of pancreatic cancer in Canada: A population-based study. AB - BACKGROUND/OBJECTIVE: The poor survival among pancreatic cancer patients accounts for a disproportionate number of cancer deaths, and there has been little or no improvement in the long-term survival of these patients. This study examines the long-term trends in incidence and relative survival of patients diagnosed with pancreatic cancer in Canada between 1992 and 2008. METHODS: We used pancreatic cancer data from the Canadian Cancer Registry. Incidence rate per age group was estimated over the aforementioned period. A flexible parametric model was used to estimate trends in one- and five-year relative survival for each age group and sex. Excess mortality rate was estimated to illustrate additional mortality due to a cancer diagnosis. RESULTS: In total, 34,577 patients with pancreatic cancer were identified, of which 49.3% were male. Mean age at diagnosis was 70.1 (SD = 12.3) years. Approximately 60.0% of patients were older than 70 years at diagnosis. There has been no change in the incidence rate of pancreatic cancer in Canada; however, it significantly decreased for men (80+) (p = 0.011). Although one-year relative survival increased over time for all patients, five-year relative survival increased only 5% for the youngest age group (<50 years). CONCLUSIONS: Overall survival of patients with pancreatic cancer remains low, although advances in chemotherapy and palliative care may have provided some improvement. Excess mortality remains highest shortly after diagnosis, which is likely attributable to the late diagnosis of pancreatic cancer. PMID- 26804004 TI - A distinctive myoepithelial hamartoma of the pancreas histologically confirmed in the mother of a previously reported patient. AB - We encountered a 62-year-old female patient with a distinctive pancreatic myoepithelial hamartoma characterized by dilated loops formed by pancreatic branch ducts. The patient, who experienced recurrent acute pancreatitis caused by pancreatic juice stasis, underwent subtotal stomach-preserving pancreatoduodenectomy, achieving remission of pancreatitis. Computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) demonstrated a honeycomb appearance of the pancreatic head, consisting largely of loop-forming dilated pancreatic branch ducts. Radiography of resected specimens demonstrated a tortuous main pancreatic duct that narrowed in the head, but communicated with the pancreatic branch ducts forming intricate loops within the lesion. Histologic examination showed dilated pancreatic ducts embedded in thick layers of smooth muscle, leading to a diagnosis of myoepithelial hamartoma. Her son shared a similar clinical course, radiologic findings, and histopathologic findings with his mother. MRCP demonstrated a honeycomb appearance of the pancreatic head in her daughter, who complained of persistent diarrhea. To our knowledge, this is the first English-language reports of such a myoepithelial hamartoma of the pancreas showing familial occurrence. PMID- 26804005 TI - Early prediction of intestinal mucosal barrier function impairment by elevated serum procalcitonin in rats with severe acute pancreatitis. AB - OBJECTIVES: The aim of this study was to evaluate serum procalcitonin (PCT) levels as a prognostic indicator of intestinal barrier function impairment in rats with severe acute pancreatitis (SAP). METHODS: Thirty-six male Sprague Dawley rats were randomly grouped into SAP group (injected sodium taurocholate via biliopancreatic duct), Gln group (gavaged with glutamine after modeling), and control group. Blood, pancreatic, and terminal ileum tissues were obtained from the rats after 6 h of modeling. Serum amylase (Amy) levels were determined using an automatic biochemical detector, while endotoxin (ET), diamine oxidase (DAO), and PCT levels were measured by ELISA test. The pathology of pancreatic and small intestine tissues were observed. PCT protein expression in intestinal tissues were detected by immunohistochemistry and western blot. RESULT: Pancreatic and intestinal injuries in Gln group were significantly lower than SAP group. Serum amylase, DAO, and PCT levels in SAP and Gln groups differed greatly and were significantly higher than control group. Immuno-histochemistry and western blot results showed that PCT protein expression levels in small intestine tissues of SAP group were higher than Gln group and control group. Serum PCT levels had a significant correlation with serum endotoxin, DAO levels and intestinal mucosal injury scores. CONCLUSION: PCT expression in serum and intestinal tissues in SAP rats increased significantly in the early stages of SAP, and was closely related to the onset and degree of intestinal barrier function impairment. Thus, our results showed that measuring serum PCT can be used to predict intestinal mucosal barrier function impairment in SAP rats. PMID- 26804006 TI - Antibiotic use in acute pancreatitis: Global overview of compliance with international guidelines. AB - INTRODUCTION: Practice guidelines for the management of acute pancreatitis make recommendations in relation to antibiotic prophylaxis and treatment in acute pancreatitis. However, it is difficult to ascertain whether this information translates into clinical practice. The aim of this study is to obtain a global overview assessing reports from across the world of the use of antibiotic use in acute pancreatitis. METHODS: A computerised literature search was performed from January 1992 to September 2015. Studies were either national physician surveys or national database reports on antibiotic prophylaxis in acute pancreatitis. Using these criteria, 10 studies were identified which comprise the final study population. RESULTS: Eight studies report on the questionnaire responses of 2397 physicians. The range of response rate was 38-96%. A separate study reported on outcome of a national insurance database outcomes in 7193 patients. The lowest incidence of use of antibiotic prophylaxis was 41% and the highest 88%. CONCLUSION: This study provides a unique global perspective on antibiotic use in acute pancreatitis and indicates that the use of antibiotics, both as prophylaxis and as treatment in this disease is widespread. PMID- 26804007 TI - Density functional theory of the CuA -like Cu2 S2 diamond core in Cu 2II(NGuaS)2 Cl2. AB - Density functional theory (DFT) calculations with localized as well as plane-wave basis functions are performed for the recently reported dicopper thiolate species Cu2 (NGuaS)2 Cl2 [NGuaS = 2-(1,1,3,3-tetramethylguanidino) benzenethiolate, C11 H16 N3 S] and its bromo derivative [Neuba et al., Angew. Chem. Int. Ed. 2012, 51, 1714.]. For both hybrid and semilocal functionals, the neutral complexes are found to have broken symmetry (BS) character, with electron paramagnetic resonance silent, antiferromagnetically coupled [Cu(2+) ...Cu(2+) ] site in which the coupling is driven by super exchange interaction within the Cu2 S2 diamond core. The accurate theoretical description of the geometric structure, however, provides a major challenge for DFT: (i) the multideterminant character of the ground state wave function has to be covered by the BS approach. It requires (ii) metageneralized gradient approximations, that is hybrid functionals with an explicit dependence on the kinetic energy of the individual orbitals: In combination with a dispersion correction, the metafunctional TPSSh results in a Cu?Cu distance close to the experimentally observed value of 2.7 A. For the negative charge state of the complex, a mixed-valent [Cu(1.5+) ...Cu(1.5+) ] electronic structure with a smaller Cu?Cu distance of 2.6 A is predicted, similar to the value of the CuA site of cytochrome c oxidase. PMID- 26804008 TI - Reconciling paradigms of abnormal pulmonary blood flow and quasi-malignant cellular alterations in pulmonary arterial hypertension. AB - In pulmonary arterial hypertension (PAH) structural and functional abnormalities of the small lung vessels interact and lead to a progressive increase in pulmonary vascular resistance and right heart failure. A current pathobiological concept characterizes PAH as a 'quasi-malignant' disease focusing on cancer-like alterations in endothelial cells (EC) and the importance of their acquired apoptosis-resistant, hyper-proliferative phenotype in the process of vascular remodeling. While changes in pulmonary blood flow (PBF) have been long-since recognized and linked to the development of PAH, little is known about a possible relationship between an altered PBF and the quasi-malignant cell phenotype in the pulmonary vascular wall. This review summarizes recognized and hypothetical effects of an abnormal PBF on the pulmonary vascular bed and links these to quasi malignant changes found in the pulmonary endothelium. Here we describe that abnormal PBF does not only trigger a pulmonary vascular cell growth program, but may also maintain the cancer-like phenotype of the endothelium. Consequently, normalization of PBF and EC response to abnormal PBF may represent a treatment strategy in patients with established PAH. PMID- 26804012 TI - Association of eating frequency with anthropometric indices and blood pressure in children and adolescents: the CASPIAN-IV Study. AB - OBJECTIVES: This study was conducted to explore the association of eating frequency (EF) with anthropometric indices and blood pressure (BP) in children and adolescents. METHODS: This nationwide cross-sectional study was performed on a multi-stage sample of 14,880 students, aged 6-18 years, living in 30 provinces in Iran. Parents were asked to report dietary intake of children as frequency of food groups and/or items. EF was defined as the sum of the daily consumption frequency of main meals and snacks. Association of EF with weight disorders, abdominal obesity, and elevated BP was assessed using different logistic regression models adjusted for potential confounding factors. RESULTS: Eating more frequently (>= 6 vs. <= 3) was found among students who were at younger age (11.91 vs. 13.29 years) (p<0.001). Students who reported an EF of 4 (OR: 0.67, CI: 0.57-0.79), 5 (OR: 0.74, CI: 0.62-0.87), and 6 (OR: 0.54, CI: 0.44-0.65) had lower odds of being obese compared to those who had EF <= 3. Having EF of 4 (OR: 0.82, CI: 0.71-0.94), 5 (OR: 0.86, CI: 0.74-0.99), and >= 6 (OR: 0.73, CI: 0.63 0.85) was related to lower prevalence of abdominal adiposity. CONCLUSION: Higher EF was associated with lower mean values of anthropometric and BP measures, as well as with lower prevalence of generalized and abdominal obesity in children and adolescents. Longitudinal studies are needed to assess the long-term effects of EF on body composition in the pediatric age group. PMID- 26804013 TI - Retrospective studies in lower urinary tract dysfunction do matter. PMID- 26804014 TI - Hospital-based surveillance of intussusception among infants. AB - OBJECTIVE: Intussusception surveillance was initiated after the nationwide introduction of live attenuated monovalent rotavirus vaccine (RV1). The objective is to assess the epidemiology of intussusception and compare the number of cases before and after the introduction of rotavirus vaccine. METHODS: Cases of intussusception occurring between March 2006 and January 2008 were identified through a prospective enhanced passive surveillance system established in sentinel state hospitals. Retrospective review of medical records was used to identify cases, which occurred in sentinel hospitals between January 2001 and February 2006. RESULTS: From 2001 to 2008, 331 intussusception cases were identified, 59.5% were male, with peak incidence among those 18-24 weeks of age. Overall <10% of cases were among infants 6-14 weeks of age (when the first dose of RV1 is administered). The most frequently observed signs or symptoms of intussusception included vomiting (89.4%), bloody stool (75.5%), and abdominal distention (71.8%). A majority (92.1%) of the case-patients required surgery for treatment; 31.8% of those who underwent surgery required bowel resection, and 13 (3.9%) died. Among the 21 hospitals that reported cases throughout the entire surveillance period (2001-2008), the number of intussusception events during 2007 (n=26) and 2008 (n=19) was not greater than the average annual number (n=31, range 24-42) during baseline years 2001-2005. CONCLUSIONS: Although this analysis did not identify an increase in intussusception cases during the two years after RV1 introduction, these results support the need for special epidemiologic methods to assess the potential link between rotavirus vaccine and this very rare adverse event. PMID- 26804016 TI - Transplantation: Reverse chimerism enables graft acceptance. PMID- 26804015 TI - Acute kidney injury: AT1 receptors modulate AKI. PMID- 26804017 TI - Anaemia: Targeting epigenetics in renal anaemia. PMID- 26804018 TI - Hypertension: Rest before blood pressure measurement: a lesson from SPRINT. PMID- 26804020 TI - Hurdles to the introduction of new therapies for immune-mediated kidney diseases. AB - Innovative immunotherapies continue to markedly benefit many disciplines in clinical medicine but disappointingly, these benefits have not translated to the treatment of kidney diseases despite encouraging findings from preclinical models of kidney dysfunction. This lack of progress in nephrology might relate to the unique biology of the kidney. More likely, this lack of progress relates to conceptual hurdles in the application of newer therapies to renal disease. In this Review we discuss seven hurdles that must be addressed in order to appropriately assess and introduce immunologic therapies for immune-mediated kidney disease: the use of appropriate criteria to define disease categories; issues relating to the heterogeneity of kidney diseases and how this heterogeneity affects approaches to treatment; issues related to the rarity of most kidney diseases; the paucity of good animal models of human kidney disease; issues relating to trial design; problems with current approaches to the identification and use of appropriate and feasible study end points; and a lack of adequate biomarkers of intrarenal inflammation and parenchymal injury. We suggest that overcoming these hurdles, in addition to searching for better therapeutic targets, will be necessary to progress the treatment of immune mediated kidney disease into a new age of drug therapy. PMID- 26804019 TI - Mitochondrial dysfunction in inherited renal disease and acute kidney injury. AB - Mitochondria are increasingly recognized as key players in genetic and acquired renal diseases. Most mitochondrial cytopathies that cause renal symptoms are characterized by tubular defects, but glomerular, tubulointerstitial and cystic diseases have also been described. For example, defects in coenzyme Q10 (CoQ10) biosynthesis and the mitochondrial DNA 3243 A>G mutation are important causes of focal segmental glomerulosclerosis in children and in adults, respectively. Although they sometimes present with isolated renal findings, mitochondrial diseases are frequently associated with symptoms related to central nervous system and neuromuscular involvement. They can result from mutations in nuclear genes that are inherited according to classic Mendelian rules or from mutations in mitochondrial DNA, which are transmitted according to more complex rules of mitochondrial genetics. Diagnosis of mitochondrial disorders involves clinical characterization of patients in combination with biochemical and genetic analyses. In particular, prompt diagnosis of CoQ10 biosynthesis defects is imperative because of their potentially reversible nature. In acute kidney injury (AKI), mitochondrial dysfunction contributes to the physiopathology of tissue injury, whereas mitochondrial biogenesis has an important role in the recovery of renal function. Potential therapies that target mitochondrial dysfunction or promote mitochondrial regeneration are being developed to limit renal damage during AKI and promote repair of injured tissue. PMID- 26804022 TI - Validation of the German version of the Perceived Stigmatization Questionnaire/Social Comfort Questionnaire in adult burn survivors. AB - OBJECTIVE: To investigate the factor structure, reliability, and validity of the German version of the Perceived Stigmatization Questionnaire/Social Comfort Questionnaire (PSQ/SCQ) in burn victims. METHODS: The PSQ/SCQ was answered by 139 adult burn survivors (age M=49.69, SD=15.16 years). Factor structure was examined using a confirmatory factor analysis (CFA). Validity was investigated through correlations between the PSQ/SCQ scales and questionnaires assessing perceived social support, burn-specific health-related quality of life, symptoms of anxiety/depression, and percent of total body surface area (TBSA) burned. Additionally, the link between perceived stigmatization/social comfort and current partnership status was investigated. RESULTS: The four-factor model showed the best fit to the data with three PSQ factors (Absence of Friendly Behavior, Confused/Staring Behavior, and Hostile Behavior) and one single SCQ factor. All PSQ/SCQ scales showed good internal consistency. Higher PSQ/lower SCQ means were related to less perceived social support, less burn-specific quality of life, and more symptoms of anxiety/depression. With the exception of a positive correlation with the PSQ subscale Confused Behavior and Staring, no other significant correlations were found between the PSQ/SCQ subscales and TBSA burned. While PSQ/SCQ scores were not linked to age or gender, less perceived social stigmatization/more social comfort was reported by participants who were currently living with a partner. CONCLUSIONS: The results indicate a four-factor structure and a good validity of the PSQ/SCQ which is in line with prior research. Further studies should investigate the application of the PSQ/SCQ in individuals with appearance distinctions that are not related to burns. PMID- 26804021 TI - Shugoshin forms a specialized chromatin domain at subtelomeres that regulates transcription and replication timing. AB - A chromosome is composed of structurally and functionally distinct domains. However, the molecular mechanisms underlying the formation of chromatin structure and the function of subtelomeres, the telomere-adjacent regions, remain obscure. Here we report the roles of the conserved centromeric protein Shugoshin 2 (Sgo2) in defining chromatin structure and functions of the subtelomeres in the fission yeast Schizosaccharomyces pombe. We show that Sgo2 localizes at the subtelomeres preferentially during G2 phase and is essential for the formation of a highly condensed subtelomeric chromatin body 'knob'. Furthermore, the absence of Sgo2 leads to the derepression of the subtelomeric genes and premature DNA replication at the subtelomeric late origins. Thus, the subtelomeric specialized chromatin domain organized by Sgo2 represses both transcription and replication to ensure proper gene expression and replication timing. PMID- 26804024 TI - Trigonal Cu2-II-Sn-VI4 (II = Ba, Sr and VI = S, Se) quaternary compounds for earth-abundant photovoltaics. AB - We propose trigonal Cu2-II-Sn-VI4 (II = Ba, Sr and VI = S, Se) quaternary compounds for earth-abundant solar cell applications. Through density functional theory calculations, we show that these compounds exhibit similar electronic and optical properties to kesterite Cu2ZnSnS4 (CZTS): high optical absorption with band gaps suitable for efficient single-junction solar cell applications. However, the trigonal Cu2-II-Sn-VI4 compounds exhibit defect properties more suitable for photovoltaic applications than those of CZTS. In CZTS, the dominant defects are the deep acceptors, Cu substitutions on Zn sites, which cause non radiative recombination and limit the open-circuit voltages of CZTS solar cells. On the contrary, the dominant defects in trigonal Cu2-II-Sn-VI4 are the shallow acceptors, Cu vacancies, similar to those in CuInSe2. Our results suggest that the trigonal Cu2-II-Sn-VI4 quaternary compounds could be promising candidates for efficient earth-abundant thin-film solar cell and photoeletrochemical water splitting applications. PMID- 26804026 TI - STAT3 and SOCS3 regulate NG2 cell proliferation and differentiation after contusive spinal cord injury. AB - NG2 cells, also known as oligodendrocyte progenitors or polydendrocytes, are a major component of the glial scar that forms after spinal cord injury. NG2 cells react to injury by proliferating around the lesion site and differentiating into oligodendrocytes and astrocytes, but the molecular mechanism is poorly understood. In this study, we tested the role of the transcription factor STAT3, and its suppressor SOCS3, in NG2 cell proliferation and differentiation after spinal cord injury. Using knockout mice in which STAT3 or SOCS3 are genetically deleted specifically in NG2 cells, we found that deletion of STAT3 led to a reduction in oligodendrogenesis, while deletion of SOCS3 led to enhanced proliferation of NG2 cells within the glial scar after spinal cord injury. Additionally, STAT3 and SOCS3 were not required for astrogliogenesis from NG2 cells after spinal cord injury. Interestingly, genetic deletion of STAT3 and SOCS3 did not have opposing effects, suggesting that SOCS3 may have targets other than the STAT3 pathway in NG2 cells after spinal cord injury. Altogether, our data show that both STAT3 and SOCS3 play important, yet unexpected, roles in NG2 cell proliferation and differentiation after spinal cord injury. PMID- 26804028 TI - Behavioral profiling as a translational approach in an animal model of posttraumatic stress disorder. AB - Diagnosis of psychiatric disorders in humans is based on comparing individuals to the normal population. However, many animal models analyze averaged group effects, thus compromising their translational power. This discrepancy is particularly relevant in posttraumatic stress disorder (PTSD), where only a minority develop the disorder following a traumatic experience. In our PTSD rat model, we utilize a novel behavioral profiling approach that allows the classification of affected and unaffected individuals in a trauma-exposed population. Rats were exposed to underwater trauma (UWT) and four weeks later their individual performances in the open field and elevated plus maze were compared to those of the control group, allowing the identification of affected and resilient UWT-exposed rats. Behavioral profiling revealed that only a subset of the UWT-exposed rats developed long-lasting behavioral symptoms. The proportion of affected rats was further enhanced by pre-exposure to juvenile stress, a well-described risk factor of PTSD. For a biochemical proof of concept we analyzed the expression levels of the GABAA receptor subunits alpha1 and alpha2 in the ventral, dorsal hippocampus and basolateral amygdala. Increased expression, mainly of alpha1, was observed in ventral but not dorsal hippocampus of exposed animals, which would traditionally be interpreted as being associated with the exposure-resultant psychopathology. However, behavioral profiling revealed that this increased expression was confined to exposed-unaffected individuals, suggesting a resilience-associated expression regulation. The results provide evidence for the importance of employing behavioral profiling in animal models of PTSD, in order to better understand the neural basis of stress vulnerability and resilience. PMID- 26804027 TI - Dentate cannabinoid-sensitive interneurons undergo unique and selective strengthening of mutual synaptic inhibition in experimental epilepsy. AB - Altered inhibition is a salient feature of hippocampal network reorganization in epilepsy. Hippocampal pyramidal cells and dentate granule cells show specific reduction in cannabinoid receptor type 1 (CB1R)-sensitive GABAergic inputs in experimental epilepsy. In the dentate gyrus, CB1Rs regulate synaptic release from accommodating interneurons (AC-INs) with adapting firing characteristics and axonal projections in the molecular layer, but not from fast-spiking basket cells (FS-BCs). However, it is not known whether the intrinsic physiology and synaptic inhibition of AC-INs responsible for CB1R-sensitive inhibition is altered in epilepsy. Using the pilocarpine-induced status epilepticus (SE) model of epilepsy, we find that the basic physiological characteristics of AC-INs in epileptic rats are not different from age-matched controls. In paired interneuronal recordings, the amplitude of unitary inhibitory synaptic currents (uIPSCs) between AC-INs doubled after SE. Non-stationary noise analysis revealed that the post-SE strengthening of synapses between AC-INs resulted from an increase in postsynaptic receptors. Baseline synaptic release and CB1R antagonist enhancement of release at synapses between AC-INs were not different between control and post-SE rats. Additionally, uIPSC amplitude in FS-BCs to AC-INs pairs was unchanged after SE indicating input-specific microcircuit alterations in inhibitory inputs to AC-INs. At the network level, AC-INs showed no reduction in spontaneous and miniature inhibitory synaptic current (sIPSC or mIPSC) frequency or amplitude after SE. However, AC-IN mIPSC amplitude was persistently enhanced in post-SE and epileptic rats. CB1R agonist reduced the amplitude and suppressed a greater proportion of sIPSCs in AC-INs from post-SE and epileptic rats demonstrating a novel, cell-type specific increase in CB1R-sensitive inhibition of AC-INs after SE. This unique post-SE strengthening of inhibition between AC INs could lead to activity-dependent suppression of AC-IN firing and compromise dentate CB1R-sensitive inhibition in epilepsy. PMID- 26804031 TI - Room temperature carbon(CO)-carbon(alpha) bond activation of ketones by rhodium(ii) porphyrins with water. AB - The mild and selective aliphatic C(CO)-C(alpha) bond activation (CCA) of ketones was successfully achieved at room temperature using rhodium(ii) porphyrins in the presence of H2O. Rh(II)(tmp) (tmp = tetrakismesitylporphyrinate dianion) disproportionates in H2O to generate the highly reactive intermediate Rh(III)(tmp)(OH) for cleaving the C-C bond of ketone, giving up to 90% of Rh(III)(tmp)(COR) and the corresponding oxidized carbonyl product in up to 76% yield within 10 min. Substrate scopes cover aliphatic as well as aromatic ketones. Both isopropyl and cyclic ketones worked well. PMID- 26804029 TI - Genetic and pharmacological evidence that endogenous nociceptin/orphanin FQ contributes to dopamine cell loss in Parkinson's disease. AB - To investigate whether the endogenous neuropeptide nociceptin/orphanin FQ (N/OFQ) contributes to the death of dopamine neurons in Parkinson's disease, we undertook a genetic and a pharmacological approach using NOP receptor knockout (NOP(-/-)) mice, and the selective and potent small molecule NOP receptor antagonist (-)-cis 1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H benzocyclohepten-5-ol (SB-612111). Stereological unbiased methods were used to estimate the total number of dopamine neurons in the substantia nigra of i) NOP( /-) mice acutely treated with the parkinsonian neurotoxin 1-methyl-4-phenyl 1,2,5,6-tetrahydropyridine (MPTP), ii) naive mice subacutely treated with MPTP, alone or in combination with SB-612111, iii) rats injected with a recombinant adeno-associated viral (AAV) vector overexpressing human mutant p.A53T alpha synuclein, treated with vehicle or SB-612111. NOP(-/-) mice showed a 50% greater amount of nigral dopamine neurons spared in response to acute MPTP compared to controls, which was associated with a milder motor impairment. SB-612111, given 4 days after MPTP treatment to mimic the clinical condition, prevented the loss of nigral dopamine neurons and striatal dopaminergic terminals caused by subacute MPTP. SB-612111, administered a week after the AAV injections in a clinically driven protocol, also increased by 50% both the number of spared nigral dopamine neurons and striatal dopamine terminals, and prevented accompanying motor deficits induced by alpha-synuclein. We conclude that endogenous N/OFQ contributes to dopamine neuron loss in pathogenic and etiologic models of Parkinson's disease through NOP receptor-mediated mechanisms. NOP receptor antagonists might prove effective as disease-modifying agents in Parkinson's disease, through the rescue of degenerating nigral dopamine neurons and/or the protection of the healthy ones. PMID- 26804030 TI - An altered peripheral IL6 response in major depressive disorder. AB - Major depressive disorder (MDD) is one of the most prevalent major psychiatric disorders with a lifetime prevalence of 17%. Recent evidence suggests MDD is not only a brain dysfunction, but a systemic disease affecting the whole body. Central and peripheral inflammatory changes seem to be a centerpiece of MDD pathology: a subset of patients show elevated blood cytokine and chemokine levels that partially normalize with symptom improvement over the course of anti depressant treatment. As this inflammatory process in MDD is poorly understood, we hypothesized that the peripheral tissues of MDD patients will respond differently to inflammatory stimuli, resulting in an aberrant transcriptional response to elevated pro-inflammatory cytokines. To test this, we used MDD patient- and control-derived dermal fibroblast cultures to investigate their response to an acute treatment with IL6, IL1beta, TNFalpha, or vehicle. Following RNA isolation and subsequent cDNA synthesis, quantitative PCR was used to determine the relative expression level of several families of inflammation responsive genes. Our results showed comparable expression of the tested genes between MDD patients and controls at baseline. In contrast, MDD patient fibroblasts had a diminished transcriptional response to IL6 in all the gene sets tested (oxidative stress response, mitochondrial function, and lipid metabolism). We also found a significant increase in baseline and IL6 stimulated transcript levels of the IL6 receptor gene. This IL6 receptor transcript increase in MDD fibroblasts was accompanied by an IL6 stimulated increase in induction of SOCS3, which dampens IL6 receptor signaling. Altogether our results demonstrate that there is an altered transcriptional response to IL6 in MDD, which may represent one of the molecular mechanisms contributing to disease pathophysiology. Ultimately we hope that these studies will lead to validation of novel MDD drug targets focused on normalizing the altered IL6 response in patients. PMID- 26804032 TI - Influence of hexabromocyclododecane and 4-nonylphenol on the regulation of cell growth, apoptosis and migration in prostatic cancer cells. AB - The aim of the present study was to determine whether hexabromocyclododecane (HBCD) or 4-nonylphenol (NP) may induce prostatic cancer progression in LNCaP cells. Androgenic effects of HBCD and NP were examined in LNCaP prostate cancer cells expressing androgen receptors (ARs). HBCD and NP increased LNCaP cell viability similar to dihydrotestosterone (DHT) by MTT assay. This phenomenon was reversed by treatment with Casodex, an AR antagonist, suggesting that they act as xenoandrogens via AR signaling pathway. In cell migration assay, HBCD and NP also enhanced LNCaP cell migration similar to DHT. To elucidate underlying mechanisms of their actions on LNCaP, transcriptional levels of cell cycle- and apoptosis related markers, including cyclin D1, cyclin E, p27, bcl-2, and bax, were determined by reverse transcription (RT)-PCR. An increase in expression cyclin D1 and cyclin E and reduction in p27 and bax mRNA levels were observed by their treatments. Western blot assay showed their alterations in translational levels of cyclin D1, cyclin E, p21, bax, and cathepsin D. Expressions of genes related to a G1/S transition of cell cycle and cathepsin D were elevated, while expression of p21 and bax was decreased. Taken together, these results indicate that HBCD and NP may enhance progression of prostate cancer by modulating growth and migration of LNCaP prostate cells by acting on cell cycle, apoptosis, and metastasis. PMID- 26804033 TI - Organ- and species-specific biological activity of rosmarinic acid. AB - Rosmarinic acid (RA), a compound found in several plant species, has beneficial properties, including anti-inflammatory and antibacterial effects. We investigated the toxicity, anti-inflammatory, and antifibrotic effects of RA using precision-cut liver slices (PCLS) and precision-cut intestinal slices (PCIS) prepared from human, mouse, and rat tissue. PCLS and PCIS were cultured up to 48 h in the absence or presence of RA. Gene expression of the inflammatory markers: IL-6, IL-8/CXCL1/KC, and IL-1beta, as well as the fibrosis markers: pro collagen 1a1, heat shock protein 47, alpha-smooth muscle actin, fibronectin (Fn2) and plasminogen activator inhibitor-1 (PAI-1) were evaluated by qPCR. RA was only toxic in murine PCIS. RA failed to mitigate the inflammatory response in most models, while it clearly reduced IL-6 and CXCL1/KC gene expression in murine PCIS at non-toxic concentrations. With regard to fibrosis, RA decreased the gene levels of Fn2 and PAI-1 in murine PCLS, and Fn2 in murine PCIS. Yet, no effect was observed on the gene expression of fibrosis markers in human and rat PCIS. In conclusion, we observed clear organ- and species-specific effects of RA. RA had little influence on inflammation. However, our study further establishes RA as a potential candidate for the treatment of liver fibrosis. PMID- 26804034 TI - Development and Symbiosis Establishment in the Cnidarian Endosymbiosis Model Aiptasia sp. AB - Symbiosis between photosynthetic algae and heterotrophic organisms is widespread. One prominent example of high ecological relevance is the endosymbiosis between dinoflagellate algae of the genus Symbiodinium and reef-building corals, which typically acquire symbionts anew each generation during larval stages. The tropical sea anemone Aiptasia sp. is a laboratory model system for this endosymbiosis and, similar to corals, produces non-symbiotic larvae that establish symbiosis by phagocytosing Symbiodinium from the environment into the endoderm. Here we generate the first overview of Aiptasia embryogenesis and larval development and establish in situ hybridization to analyze expression patterns of key early developmental regulators. Next, we quantify morphological changes in developing larvae and find a substantial enlargement of the gastric cavity over time. Symbiont acquisition starts soon after mouth formation and symbionts occupy a major portion of the host cell in which they reside. During the first 14 days of development, infection efficiency remains constant while in contrast, localization of phagocytosed symbionts changes, indicating that the occurrence of functional phagocytosing cells may be developmentally regulated. Taken together, here we provide the essential framework to further develop Aiptasia as a model system for the analysis of symbiosis establishment in cnidarian larvae at the molecular level. PMID- 26804035 TI - Maternal mortality in New York--Looking back, looking forward. AB - New York City was ahead of its time in recognizing the issue of maternal death and the need for proper statistics. New York has also documented since the 1950s the enormous public health challenge of racial disparities in maternal mortality. This paper addresses the history of the first Safe Motherhood Initiative (SMI), a voluntary program in New York State to review reported cases of maternal deaths in hospitals. Review teams found that timely recognition and intervention in patients with serious morbidity could have prevented many of the deaths reviewed. Unfortunately the program was defunded by New York State. The paper then focuses on the revitalization of the SMI in 2013 to establish three safety bundles across the state to be used in the recognition and treatment of obstetric hemorrhage, severe hypertension in pregnancy, and the prevention of venous thromboembolism; and their introduction into 118 hospitals across the state. The paper concludes with a look to the future of the coordinated efforts needed by various organizations involved in women's healthcare in New York City and State to achieve the goal of a review of all maternal deaths in the state by a multidisciplinary team in a timely manner so that appropriate feedback to the clinical team can be given and care can be modified and improved as needed. It is the authors' opinion that we owe this type of review to the women of New York who entrust their care to us. PMID- 26804036 TI - Ethical challenges in the new world of maternal-fetal surgery. AB - This article explores some of the complex ethical challenges that exist in the field of fetal diagnosis and treatment, especially surrounding maternal-fetal surgery. The rise of these new treatments force us to reconsider who or what is the fetus, what are our obligations to the fetus, and what are the limits to those obligations. In addition, we will consider provider and professional biases, disability issues, and how maternal-fetal surgery has, for a select group of women, changed the very experience of motherhood. PMID- 26804037 TI - Prognostic Value of Drinking Status and Aldehyde Dehydrogenase 2 Polymorphism in Patients With Head and Neck Squamous Cell Carcinoma. AB - BACKGROUND: The association between alcohol drinking, aldehyde dehydrogenase 2 (ALDH2) polymorphism, and survival in patients with head and neck squamous cell carcinoma (HNSCC) remains unclear. METHODS: We performed a retrospective cohort study of 267 HNSCC patients at Aichi Cancer Center. Of these, 65 patients (24%) were non-drinkers, 104 (39%) were light drinkers (ethanol <46 g or <5 days/week), 46 (17%) were moderate drinkers (ethanol intake 46-68 g/day and >=5 days/week), and 52 (20%) were heavy drinkers (ethanol intake >=69 g and >=5 days/week). The prognostic value of pre-treatment drinking status and ALDH2 polymorphism was investigated using multivariate proportional hazard models. RESULTS: Drinking status was associated with disease-free survival (DFS) in HNSCC patients, with marginal statistical significance (5-year DFS: 67.9% [95% confidence interval {CI}, 53.8-78.4%] for non-drinkers, 57.6% [95% CI, 47.4-66.6%] for light drinkers, 46.1% [95% CI, 30.8-60.1%] for moderate drinkers, and 43.5% [95% CI, 29.3-56.9%] for heavy drinkers; P = 0.088). However, this association lost significance when multivariate analyses were adjusted for established prognostic factors. ALDH2 genotype was not significantly associated with DFS in HNSCC patients (5-year DFS: 85.7% [95% CI, 53.9-96.2%] for Lys/Lys, 56.2% [95% CI, 47.4 64.1%] for Glu/Lys, and 50.5% [95% CI, 40.3-59.7%] for Glu/Glu; P = 0.154). After stratification by ALDH2 genotype, we observed a significant positive dose response relationship between drinking status and DFS in HNSCC patients with ALDH2 Glu/Glu (Ptrend = 0.029). CONCLUSIONS: In this study, we identified a significant positive dose-response relationship between pre-treatment drinking status and DFS in HNSCC patients with ALDH2 Glu/Glu. To confirm this association, further study is warranted. PMID- 26804038 TI - Standardized Prevalence Ratios for Atrial Fibrillation in Adult Dialysis Patients in Japan. AB - BACKGROUND: While it is assumed that dialysis patients in Japan have a higher prevalence of atrial fibrillation (AF) than the general population, the magnitude of this difference is not known. METHODS: Standardized prevalence ratios (SPRs) for AF in dialysis patients (n = 1510) were calculated compared to data from the general population (n = 26 454) living in the same area. RESULTS: The prevalences of AF were 3.8% and 1.6% in dialysis patients and the general population, respectively. In male subjects, these respective values were 4.9% and 3.3%, and in female subjects they were 1.6% and 0.6%. The SPRs for AF were 2.53 (95% confidence interval [CI], 1.88-3.19) in all dialysis patients, 1.80 (95% CI, 1.30 2.29) in male dialysis patients, and 2.13 (95% CI, 0.66-3.61) in female dialysis patients. CONCLUSIONS: The prevalence of AF in dialysis patients was twice that in the population-based controls. Since AF strongly contributes to a higher risk of cardiovascular mortality and morbidity in the general population, further longitudinal studies should be conducted regarding the risk of several outcomes attributable to AF among Japanese dialysis patients. PMID- 26804040 TI - Elective induction of labour on maternal request: why do we continue to deny women this option? PMID- 26804041 TI - A miniaturized microbial fuel cell with three-dimensional graphene macroporous scaffold anode demonstrating a record power density of over 10,000 W m(-3) . AB - A microbial fuel cell (MFC) is a bio-inspired renewable energy converter which directly converts biomass into electricity. This is accomplished via the unique extracellular electron transfer (EET) of a specific species of microbe called the exoelectrogen. Many studies have attempted to improve the power density of MFCs, yet the reported power density is still nearly two orders of magnitude lower than other power sources/converters. Such a low performance can primarily be attributed to two bottlenecks: (i) ineffective electron transfer from microbes located far from the anode and (ii) an insufficient buffer supply to the biofilm. This work takes a novel approach to mitigate these two bottlenecks by integrating a three-dimensional (3D) macroporous graphene scaffold anode in a miniaturized MFC. This implementation has delivered the highest power density reported to date in all MFCs of over 10,000 W m(-3). The miniaturized configuration offers a high surface area to volume ratio and improved mass transfer of biomass and buffers. The 3D graphene macroporous scaffold warrants investigation due to its high specific surface area, high porosity, and excellent conductivity and biocompatibility which facilitates EET and alleviates acidification in the biofilm. Consequently, the 3D scaffold houses an extremely thick and dense biofilm from the Geobacter-enriched culture, delivering an areal/volumetric current density of 15.51 A m(-2)/31,040 A m(-3) and a power density of 5.61 W m( 2)/11,220 W m(-3), a 3.3 fold increase when compared to its planar two dimensional (2D) control counterparts. PMID- 26804042 TI - Solution NMR characterization of apical membrane antigen 1 and small molecule interactions as a basis for designing new antimalarials. AB - Plasmodium falciparum apical membrane antigen 1 (PfAMA1) plays an important role in the invasion by merozoites of human red blood cells during a malaria infection. A key region of PfAMA1 is a conserved hydrophobic cleft formed by 12 hydrophobic residues. As anti-apical membrane antigen 1 antibodies and other inhibitory molecules that target this hydrophobic cleft are able to block the invasion process, PfAMA1 is an attractive target for the development of strain transcending antimalarial agents. As solution nuclear magnetic resonance spectroscopy is a valuable technique for the rapid characterization of protein ligand interactions, we have determined the sequence-specific backbone assignments for PfAMA1 from two P. falciparum strains, FVO and 3D7. Both selective labelling and unlabelling strategies were used to complement triple resonance experiments in order to facilitate the assignment process. We have then used these assignments for mapping the binding sites for small molecules, including benzimidazoles, pyrazoles and 2-aminothiazoles, which were selected on the basis of their affinities measured from surface plasmon resonance binding experiments. Among the compounds tested, benzimidazoles showed binding to a similar region on both FVO and 3D7 PfAMA1, suggesting that these compounds are promising scaffolds for the development of novel PfAMA1 inhibitors. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26804043 TI - The relation between child feeding problems as measured by parental report and mealtime behavior observation: A pilot study. AB - Because feeding problems have clear negative consequences for both child and caretakers, early diagnosis and intervention are important. Parent-report questionnaires can contribute to early identification, because they are efficient and typically offer a 'holistic' perspective of the child's eating in different contexts. In this pilot study, we aim to explore the concurrent validity of a short screening instrument (the SEP, which is the Dutch MCH-FS) in one of its target populations (a group of premature children) by comparing the total score with the observed behavior of the child and caretaker during a regular home meal. 28 toddlers (aged 9-18 months) and their caretakers participated in the study. Video-observations of the meals were coded for categories of eating behavior and parent-child interaction. The results show that the total SEP-score correlates with food refusal, feeding efficiency, and self-feeding, but not with negative affect and parental instructions. This confirms that the SEP has a certain degree of concurrent validity in the sense that its total score is associated with specific 'benchmark' feeding behaviors: food refusal, feeding efficiency and autonomy. Future studies with larger samples are needed to generalize the findings from this pilot to a broader context. PMID- 26804049 TI - Do Nonopioid Medications Provide Effective Analgesia in Adult Patients With Acute Renal Colic? PMID- 26804044 TI - Formaldehyde and acetaldehyde exposure and risk characterization in California early childhood education environments. AB - Little information is available about air quality in early childhood education (ECE) facilities. We collected single-day air samples in 2010-2011 from 40 ECE facilities serving children <=6 years old in California and applied new methods to evaluate cancer risk in young children. Formaldehyde and acetaldehyde were detected in 100% of samples. The median (max) indoor formaldehyde and acetaldehyde levels (MUg/m3 ) were 17.8 (48.8) and 7.5 (23.3), respectively, and were comparable to other California schools and homes. Formaldehyde and acetaldehyde concentrations were inversely associated with air exchange rates (Pearson r = -0.54 and -0.63, respectively; P < 0.001). The buildings and furnishings were generally >5 years old, suggesting other indoor sources. Formaldehyde levels exceeded California 8-h and chronic Reference Exposure Levels (both 9 MUg/m3 ) for non-cancer effects in 87.5% of facilities. Acetaldehyde levels exceeded the U.S. EPA Reference Concentration in 30% of facilities. If reflective of long-term averages, estimated exposures would exceed age-adjusted 'safe harbor levels' based on California's Proposition 65 guidelines (10-5 lifetime cancer risk). Additional research is needed to identify sources of formaldehyde and acetaldehyde and strategies to reduce indoor air levels. The impact of recent California and proposed U.S. EPA regulations to reduce formaldehyde levels in future construction should be assessed. PMID- 26804050 TI - Cobalt-Catalyzed Annulation of Salicylaldehydes and Alkynes to Form Chromones and 4-Chromanones. AB - A unique cobalt(I)-diphosphine catalytic system has been identified for the coupling of salicylaldehyde (SA) and an internal alkyne affording a dehydrogenative annulation product (chromone) or a reductive annulation product (4-chromanone) depending on the alkyne substituents. Distinct from related rhodium(I)- and rhodium(III)-catalyzed reactions of SA and alkynes, these annulation reactions feature aldehyde C-H oxidative addition of SA and subsequent hydrometalation of the C=O bond of another SA molecule as common key steps. The reductive annulation to 4-chromanones also involves the action of Zn as a stoichiometric reductant. In addition to these mechanistic features, the Co(I) catalysis described herein is complementary to the Rh(I) - and Rh(III) -catalyzed reactions of SA and internal alkynes, particularly in the context of chromone synthesis. PMID- 26804051 TI - 2-Aminoacetophenone Is the Main Volatile Phase I Skatole Metabolite in Pietrain * Baden-Wurttemberg Hybrid Type Boars. AB - Skatole metabolites have been considered as putative contributors to boar taint. Recently, 2-aminoacetophenone, a volatile phase I skatole metabolite, was identified in back fat samples from boars of Pietrain * Baden-Wurttemberg hybrid type. This paper addresses the question of the physiological origin of the observed 2-aminoacetophenone in these pigs. Microsomal fractions from nine boars were isolated, and formation of skatole metabolites was subsequently analyzed by stable-isotope dilution analysis (SIDA) using headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME/GC-MS). Significant breed-related differences in phase I skatole metabolism were observed, explaining the high levels of 2-aminoacetophenone in Pietrain * Baden-Wurttemberg hybrid type boars. PMID- 26804052 TI - 23andMe markets carrier screening service directly to consumers: Service offers results on carrier status, raises concerns among geneticists. PMID- 26804053 TI - Children with developmental delays rarely referred to geneticists: Study finds just 5% of primary care physicians would refer infants for genetics evaluation. PMID- 26804055 TI - Astroglial Activation and Tau Hyperphosphorylation Precede to Neuron Loss in a Neurodegenerative Mouse Model. PMID- 26804057 TI - Engineered bacterial polyester hydrolases efficiently degrade polyethylene terephthalate due to relieved product inhibition. AB - Recent studies on the enzymatic degradation of synthetic polyesters have shown the potential of polyester hydrolases from thermophilic actinomycetes for modifying or degrading polyethylene terephthalate (PET). TfCut2 from Thermobifida fusca KW3 and LC-cutinase (LCC) isolated from a compost metagenome are remarkably active polyester hydrolases with high sequence and structural similarity. Both enzymes exhibit an exposed active site in a substrate binding groove located at the protein surface. By exchanging selected amino acid residues of TfCut2 involved in substrate binding with those present in LCC, enzyme variants with increased PET hydrolytic activity at 65 degrees C were obtained. The highest activity in hydrolyzing PET films and fibers were detected with the single variant G62A and the double variant G62A/I213S. Both variants caused a weight loss of PET films of more than 42% after 50 h of hydrolysis, corresponding to a 2.7-fold increase compared to the wild type enzyme. Kinetic analysis based on the released PET hydrolysis products confirmed the superior hydrolytic activity of G62A with a fourfold higher hydrolysis rate constant and a 1.5-fold lower substrate binding constant than those of the wild type enzyme. Mono-(2 hydroxyethyl) terephthalate is a strong inhibitor of TfCut2. A determination of the Rosetta binding energy suggested a reduced interaction of G62A with 2PET, a dimer of the PET monomer ethylene terephthalate. Indeed, G62A revealed a 5.5-fold lower binding constant to the inhibitor than the wild type enzyme indicating that its increased PET hydrolysis activity is the result of a relieved product inhibition by mono-(2-hydroxyethyl) terephthalate. Biotechnol. Bioeng. 2016;113: 1658-1665. (c) 2016 Wiley Periodicals, Inc. PMID- 26804056 TI - Loss of delta-GABAA receptor-mediated tonic currents in the adult prelimbic cortex following adolescent alcohol exposure. AB - Delayed maturation of the adolescent prefrontal cortex may render it particularly vulnerable to insults, including those associated with drugs of abuse. Using a rat model of binge alcohol exposure, the present study examined the effect of adolescent intermittent ethanol (AIE) exposure during postnatal days 28-42 on gamma-aminobutyric acid (GABA)ergic neurotransmission in the prelimbic cortex. In control rats, patch-clamp electrophysiology in acute slices obtained at different postnatal ages revealed a developmental increase in the GABAA receptor-mediated tonic current in layer V pyramidal neurons but no change in layers II/III when measured in the adult. In slices from AIE-exposed rats, the amplitude of the tonic current was significantly reduced compared with controls when tested at postnatal days 45, 60 and 90-120. This AIE-induced reduction in tonic current was found to reflect attenuation of currents mediated by delta-subunit containing receptors. Consistent with this, facilitation of the tonic current by bath application of either ethanol or allopregnanolone was attenuated in slices from AIE-exposed adult rats compared with control rats. However, expression of this facilitation as a percent of the amplitude of the total current mediated by delta GABAA receptors revealed that AIE did not alter their sensitivity to either agonist. Lastly, immunohistochemistry and Western blot analysis revealed no change in the expression of delta-GABAA subunits or their surface expression. Taken together, these studies reveal that AIE exposure results in persistent deficits in delta-GABAA tonic currents in the adult prelimbic cortex that may contribute to deficits in decision-making and behavioral control in adulthood. PMID- 26804060 TI - Tryptophan biosynthesis is important for resistance to replicative stress in Saccharomyces cerevisiae. AB - Acute tryptophan depletion is used to induce low levels of serotonin in the brain. This method has been widely used in psychiatric studies to evaluate the effect of low levels of serotonin, and is generally considered a safe and reversible procedure. Here we use the budding yeast Saccharomyces cerevisiae to study the effects of tryptophan depletion on growth rate upon exposure to DNA damaging agents. Surprisingly, we found that budding yeast undergoing tryptophan depletion were more sensitive to DNA-damaging agents such as methyl methanesulphonate (MMS) and hydroxyurea (HU). We found that this defect was independent of several DNA repair pathways, such as homologous recombination, base excision repair and translesion synthesis, and that this damage sensitivity was not due to impaired S-phase signalling. Upon further analysis, we found that the DNA-damage sensitivity of tryptophan depletion was likely due to impaired protein synthesis. These studies describe an important source of variance in budding yeast when using tryptophan as an auxotrophic marker, particularly on studies focusing on DNA repair, and suggest that further testing of the effect of tryptophan depletion on DNA repair in mammalian cells is warranted. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26804061 TI - Shikonin Derivative DMAKO-05 Inhibits Akt Signal Activation and Melanoma Proliferation. AB - DMAKO-05((S)-1-((5E,8E)-5,8-bis(hydroxyimino)-1,4-dimethoxy-5,8-dihydronaphthalen 2-yl)-4-methylpent-3-enyl 3-methylbutanoate) is a novel oxime derivative of shikonin, the major component extracted from Chinese herb Lithospermun erythrorhizon. Here, we report that DMAKO-05 had an antitumor activity against mouse melanoma cell line B16F0. Our studies indicated that DMAKO-05 not only inhibited B16F0 proliferation and migration but also led to cell cycle arrest at G1 phase and cell apoptosis, in which DMAKO-05 triggered mitochondrial-mediated apoptosis signal including caspase-9/3 and PARP. In response to DMAKO-05 treatment, the Akt-mediated survival signals were remarkably attenuated in B16F0 cells. Collectively, DMAKO-05 has a strong cytotoxicity in B16F0 cells via inhibiting Akt activation, inducing G1 arrest, and promoting B16F0 cell apoptosis. DMAKO-05 might serve as a potential candidate lead compound for melanoma. PMID- 26804063 TI - Apolipoproteins, lipids and risk of cancer. AB - The epidemiological evidence for an obesity-cancer association is solid, whereas the association between obesity-associated lipoprotein levels and cancer is less evident. We investigated circulating levels of Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB), LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) and association to risk of overall cancer and common cancer forms. The Malmo Diet and Cancer Study, a population-based prospective cohort study, enrolled 17,035 women and 11,063 men (1991-1996). Incident cancer cases were ascertained by record linkage with the Swedish Cancer Registry until end of follow-up, January 1, 2012. Baseline serum levels of ApoA1 and ApoB were analyzed for the entire cohort and HDL-C and LDL-C levels in 5,281 participants. Hazard ratios, with 95% confidence interval, were calculated using Cox's proportional hazards analysis. In the entire cohort, none of the exposures were related to overall cancer risk (HRadj ApoA1 = 0.98, 95%CI: 0.95,1.01; HRadj ApoB = 1.01, 95%CI: 0.98-1.04). Among men, ApoB was positively associated with cancer risk (HRadj ApoB = 1.06, 95%CI: 1.01,1.10). Female breast cancer risk was inversely associated with ApoB (HRadj = 0.92, 95%CI: 0.86,0.99). Among both genders, ApoA1 was inversely associated with lung cancer risk (HRadj = 0.88, 95%CI: 0.80,0.97), whereas high ApoB increased lung cancer risk (HRadj = 1.08, 95%CI: 0.99,1.18). Colorectal cancer risk was increased with high ApoB (HRadj = 1.08, 95%CI: 1.01,1.16) among both genders. Apolipoprotein levels were not associated with prostate cancer incidence. Circulating levels of apolipoproteins are associated with overall cancer risk in men and across both genders with breast, lung and colorectal cancer risk. Validation of these findings may facilitate future primary prevention strategies for cancer. PMID- 26804062 TI - Progesterone-Regulated Endometrial Factors Controlling Implantation. AB - The steroid hormone progesterone (P), acting via the progesterone receptor (PR) isoforms, PR-A and PR-B, exerts a profound influence on uterine functions during early gestation. In recent years, chromatin immunoprecipitation-sequencing in combination with microarray-based gene expression profiling analyses have revealed that the PR isoforms control a substantially large cistrome and transcriptome during endometrial differentiation in the human and the mouse. Genetically engineered mouse models have established that several PR-regulated genes, such as Ihh, Bmp2, Hoxa10, and Hand2, are essential for implantation and decidualization. PR-A and PR-B also collaborate with other transcription factors, such as FOS, JUN, C/EBPbeta and STAT3, to regulate the expression of many target genes that functions in concert to properly control uterine epithelial proliferation, stromal differentiation, angiogenesis, and local immune response to render the uterus 'receptive' and allow embryo implantation. This review article highlights recent work describing the key PR-regulated pathways that govern critical uterine functions during establishment of pregnancy. PMID- 26804064 TI - Effects of a Stepwise Multidisciplinary Intervention for Challenging Behavior in Advanced Dementia: A Cluster Randomized Controlled Trial. AB - OBJECTIVES: To assess whether implementation of a stepwise multicomponent intervention (STA OP!) is effective in reducing challenging behavior and depression in nursing home residents with advanced dementia. DESIGN: Cluster randomized controlled trial. SETTING: Twenty-one clusters (single independent nursing home units) in 12 nursing homes within the Netherlands. PARTICIPANTS: Residents with advanced dementia (N = 288). INTERVENTION: Staff working on intervention units received comprehensive stepwise multidisciplinary training; the control condition received training on general nursing skills, dementia management and pain without the stepwise component. MEASUREMENTS: The primary outcome was agitation (Cohen-Mansfield Agitation Inventory (CMAI)). Secondary outcomes included psychotropic medication use, neuropsychiatric symptoms (Neuropsychiatric Inventory-Nursing Home version (NPI-NH)), and symptoms of depression (Cornell Scale for Depression in Dementia (CSDD), Minimum Dataset Depression Rating Scale (MDS-DRS)). Measurements were made at baseline and 3 and 6 months after the intervention. Multilevel analysis and logistical generalized estimating equations were used to test treatment and time effects. Analysis was on an intention-to-treat basis. RESULTS: Multilevel modeling revealed an overall effect of the intervention on challenging behavior and depression; CMAI (mean difference -4.07 points, 95% confidence interval = (CI) = -7.90 to -0.24, P = .02), NPI-NH (mean difference -3.57 points, 95% CI = -6.30 to -0.84, P = .005), CSDD (mean difference -1.59 points, 95% CI = -2.49 to -0.69, P < .001), and MDS DRS (mean difference -0.96 points, 95% CI = -1.40 to -0.52, P < .001) scores were significantly lower in the intervention condition than the control condition. There was a significant reduction of antidepressants (N06A) (OR = 0.32); nonsignificant reductions of antipsychotics (N05A), anxiolytics (N05B), and hypnotic-sedatives (N05C) (odds ratios = 0.69 to 0.90). CONCLUSION: For nursing home residents with advanced dementia and challenging behavior, providing staff with comprehensive training in behavioral management, resulted in improved behavior and less psychotropic medication use. PMID- 26804066 TI - Freeze-dried stallion spermatozoa: evaluation of two chelating agents and comparative analysis of three sperm DNA damage assays. AB - During the freeze-drying procedure, sperm DNA might become damaged by both freezing and drying stresses. Sperm DNA status can be detected using well established assays; however, most techniques are expensive and involve elaborate protocols and equipment. Indirect assessments can provide alternative strategies. The objective of this study was to compare a simple test of DNA status using Diff Quik (DQ) with two established procedures: acridine orange test (AOT) and sperm chromatin dispersion (SCD) on freeze-dried (FD) stallion spermatozoa. Ejaculated spermatozoa from three stallions were freeze-dried in basic medium supplemented with two different chelating agents: EGTA or EDTA. After rehydration, the spermatozoa were subjected to DNA damage detection using a SCDt, AOT and DQ stain simultaneously. The results showed that the DNA damage levels in the EGTA group were significantly lower than those in the EDTA group. AOT detected a significantly higher proportion of spermatozoa with fragmented DNA than DQ and SCD. The results of the SCD test and DQ stain exhibited a significant positive correlation for DNA fragmentation (r = 0.528), whereas a negative correlation was observed between SCD, DQ and AOT (r = -0.134 and r = -0.332 respectively). The present study shows that both the SCD test and DQ assay are effective methods for detecting FD stallion sperm DNA fragmentation, whereas using of AOT is questionable. PMID- 26804105 TI - Improving a web-based employability intervention for work-disabled employees: results of a pilot economic evaluation. AB - Purpose The purpose of this study is to improve web-based employability interventions for employees with work-related health problems for both intervention content and study design by means of a pilot economic evaluation. Methods Uptake rate analysis for the intervention elements, cost effectiveness, cost utility and subgroup analyses were conducted to identify potential content related intervention improvements. Differences in work ability and quality adjusted life years and overall contribution of resource items to the total costs were assessed. These were used to guide study design improvements. Results Sixty three participants were a-select allocated to either the intervention (n = 29) or the control (n = 34) group. Uptake regarding the intervention elements ranged between 3% and 70%. Cost-effectiveness and cost-utility analyses resulted in negative effects although higher total costs. Incremental effects were marginal (work ability -0.51; QALY -0.01). Conclusions The web-based tool to enhance employability among work disabled employees requires improvements regarding targeting and intensity; outcome measures selected and collection of cost data. With respect to the studies of disability and rehabilitation, the findings and methods presented in this pilot economic evaluation could guide the assessment of future assistive "e-health" technologies. IMPLICATIONS FOR REHABILITATION The methods presented in this pilot economic evaluation have large potentials to guide the assessment of future assistive e-health technologies addressing work disabilities. The findings show that the web-based tool requires content related improvements with respect to targeting and intensity to enhance employability among work disabled employees. The findings show that the web-based tool would benefit from improvements related to the study design by more adequately selecting and collecting both outcome measures and cost data. The burden attributable to large-scale studies and implementation issues were prevented as the outcomes of the pilot economic evaluation did not support the implementation of the web-based tool. PMID- 26804106 TI - Metabolic syndrome does not always play a critical role in decreased GFR. AB - BACKGROUND: There is a paucity of literature available as to the relationship between different levels of each metabolic syndrome (MetS) component and decreased GFR. In the present study, we aimed to demonstrate whether MetS always plays a critical role in decreased GFR. METHODS: A cross-sectional study was conducted between February 2010 and September 2012, with 75,468 adults enrolled undergoing measurements of blood pressure as well as tests of blood and urine samples. Univariate and multivariable logistic regression analyses were performed to estimate the odds ratio (OR) with 95% confidence intervals (CI), and the chi square test was used for categorical variables and described as a percentage. RESULTS: Of the 75,468 participants, 350 (0.5%) subjects met criteria for the decreased GFR, with a mean age of 48.79 +/- 13.76 years. After adjustment for age, diastolic blood pressure and high-density lipoprotein were inversely related to decreased estimated glomerular filtration rate (eGFR) in multivariable analyses, with an OR (95% CI) of 0.57 (0.39-0.84) and 0.41 (0.24-0.72), respectively. The prevalence rate of CKD in critical group was 0.73% (154 of 21,127) and 0% (0 of 370) in noncritical group. In analysis stratified by the type of MetS components, the differences in noncritical group and the reference group were not statistically significant (chi(2 )=( )1.349, p > 0.05). CONCLUSIONS: MetS does not always play a critical role in decreased GFR, with different levels of individual components of MetS exerting idiosyncratic effects in decreased eGFR. In fact, patients with abnormal body mass index, high triglycerides, and elevated fasting plasma glucose would not have impact on decreased GFR. PMID- 26804107 TI - Z-Shaped Pentaleno-Acene Dimers with High Stability and Small Band Gap. AB - Acene-based materials have promising applications for organic electronics but the major constrain comes from their poor stability. Herein a new strategy to stabilize reactive acenes, by fusion of an anti-aromatic pentalene unit onto the zigzag edges of two acene units to form a Z-shaped acene dimer, is introduced. The Z-shaped acene dimers are extremely stable and show a small energy gap resulting from intramolecular donor-acceptor interactions. X-ray crystallographic analysis revealed their unique geometry and one-dimensional slip-stack columnar structure. Besides optical and electrochemical characterizations, solution processed field-effect transistors were also fabricated. PMID- 26804108 TI - Effect of source-separated urine storage on estrogenic activity detected using bioluminescent yeast Saccharomyces cerevisiae. AB - The objective was to demonstrate that a microbial whole cell biosensor, bioluminescent yeast, Saccharomyces cerevisiae (BMAEREluc/ERalpha) can be applied to detect overall estrogenic activity from fresh and stored human urine. The use of source-separated urine in agriculture removes a human originated estrogen source from wastewater influents, subsequently enabling nutrient recycling. Estrogenic activity in urine should be diminished prior to urine usage in agriculture in order to prevent its migration to soil. A storage period of 6 months is required for hygienic reasons; therefore, estrogenic activity monitoring is of interest. The method measured cumulative female hormone-like activity. Calibration curves were prepared for estrone, 17beta-estradiol, 17alpha ethinylestradiol and estriol. Estrogen concentrations of 0.29-29,640 MUg L(-1) were detectable while limit of detection corresponded to 0.28-35 MUg L(-1) of estrogens. The yeast sensor responded well to fresh and stored urine and gave high signals corresponding to 0.38-3,804 MUg L(-1) of estrogens in different urine samples. Estrogenic activity decreased during storage, but was still higher than in fresh urine implying insufficient storage length. The biosensor was suitable for monitoring hormonal activity in urine and can be used in screening anthropogenic estrogen-like compounds interacting with the receptor. PMID- 26804111 TI - Harry H. Harman (1913-1376). PMID- 26804112 TI - Factor Analytic Studies Of Human Brain Damage: I. First And Second-Order Factors And Their Brain Correlates. AB - This report is concerned with identifying the first and second-order cognitive factors underlying a battery of 49 measures taken from 22 brain damage tests. The test scores from 176 brain damaged patients between 16 and 65 years of age were intercorrelated and subjected to first-order alpha factoring followed by promax rotation to oblique simple structure. Ten of the 13 first-order factors extracted were interpretable, six of them being perceptual in nature and four being of a more conceptual nature. The perceptual factors include: perceptual organization, perceptual-motor speed, pattern recognition, temporal resolution, spatial orientation, and figure-ground identification. The conceptual factors include verbal comprehension, memory, and two abstraction factors. A second-order alpha factoring was performed on the matrix of correlations among the 13 primaries. Three of the five second-order factors extracted were interpretable. They were identified as perceptual integration (subsuming the first-order factors of perceptual organization, perceptual-motor speed, and temporal resolution), verbal memory (subsuming verbal comprehension and memory), and visualization (subsuming spatial orientation and figure-ground identification). Although factor interpretations were based primarily on the patterns of high loading variables, they were also influenced by lesion effects observed in this and related studies. About half the interpretable factors are relatively localized (i.e., confined to one or two lobes of one hemisphere), with the other half more diffuse (i.e., multi-lobed, combined with laterality or bilaterality). The more localized factors include the right hemisphere factors of perceptual-motor speed, temporal resolution, and spatial orientation, and the left hemisphere factors of verbal comprehension, memory, and verbal memory. The more neurally diffuse factors include the second-order factors and such broad gauged first-order factors as abstraction I and II, and pattern recognition. Furthermore, same lobe, bilaterally hemispheric effects were rare, and only four factors (memory, verbal memory, visualization, and abstraction I) were correlated with sub-cortical lesions. PMID- 26804113 TI - A Nonparametric Coefficient Of Internal Consistency. AB - This paper discusses a frequency based, nonparametric measure of internal test consistency, referred to herein as coefficient alphatau, which allows facile measurement of the significance of differences in internal consistency between tests, administrations, or scoring methods. It also permits analysis of psychological tests containing items with discrete categories of response, yielding nominal scale data. Use of alphatau encourages flexibility in test construction, since multiple dimensions can be incorporated into individual test items. PMID- 26804114 TI - Simultaneous Processing Of Multiple Stimulus Dimensions Among Paranoid And Nonparanoid Schizophrenics. AB - In the first study, paranoid and nonparanoid schizophrenics and normals made dichotamous conceptual judgments about multidimensional visual stimuli. While the schizophrenics were not significantly inferior with respect to efficiency in multidimensional stimulus combination and did not display abnormal patterns of dimensional combination, they were less sensitive to interstimulus variation in the relevant attributes. In the second study, subjects performed judgments of multidimensional similarity among verbal stimuli. Results indicated the several semantic dimensions of variation to be no less "accessable" to the schizophrenics when considered individually, but that these subject, especially those classified as paranoid, were less effective in combining the dimensions for multidimensional judgments. Discussion centered on theoretical reasons for deficit with the verbal stimuli and the nature of the semantic dimensions involved. PMID- 26804115 TI - Structural Equations As An Aid In The Interpretation Of The Non-Orthogonal Analysis Of Variance. AB - Various computational methods for non-orthogonal analysis of variance designs lead to tests of different hypotheses. The purpose of this paper is to define the structural equations underlying these hypotheses and thus to indicate under what conditions one or more methods may be preferable. PMID- 26804116 TI - An Assessment Of The Impact Of Economic Factors On Planned Fertility In New York City, 1970. AB - The economic theory of fertility predicts that fertility will be positively related to financial resources and negatively related to child costs. This theory is shown to be, in essence, a motivational theory, and as such relevant to predicting planned fertility but not necessarily unplanned childbearing. It is also expected that neither the probability of planned parenthood nor the influence of economic factors will be constant across all age groups of potential mothers. An empirical test of these relationships is presented using the age specific fertility rates of 338 New York City areas. The relationships of three sets of social indicators representing the hypothetically relevant factors are determined. The importance of these factors is assessed by means of their multiple and multiple partial correlations. PMID- 26804117 TI - Characteristics Distinguishing Vocational Education Students From General And Academic Students. AB - This study attempted to identify variables from a lengthy omnibus questionnaire and a set of test scores that would distinguish students in high school vocational education programs from those in academic and general programs. The sample of 16,409 students was selected from a national probability sample. Analyses were performed for five groups, and all results were cross-validated. The results indicated that vocational students were lower than academic students in tested academic ability. Although vocational students were as low in academic ability as were general students, vocational students achieved higher school grades, were less alienated, and focused more on the work world. PMID- 26804118 TI - KRAS, HRAS and EGFR Mutations in Sporadic Sebaceous Gland Hyperplasia. AB - Sporadic sebaceous gland hyperplasia (SGH) is a benign skin lesion, with a high prevalence in the general population. Although SGH has been attributed to both extrinsic and intrinsic factors, the underlying genetic changes have not yet been characterized. Recently, HRAS and KRAS mutations have been identified in sebaceous naevus, a hamartoma sharing histological characteristics with SGH. Therefore we screened 43 SGH for activating mutations in RAS genes and other oncogenes. We identified a wide spectrum of mutually exclusive activating HRAS (8/43), KRAS (11/43) and EGFR mutations (7/31) in altogether 60% of the lesions investigated. A RAS and EGFR wildtype status was found in 15 normal sebaceous glands in the head and neck area. Our findings indicate that activating HRAS, KRAS and EGFR mutations play a major role in the pathogenesis of sporadic SGH. These results support the concept that SGH is a true benign neoplasm rather than a reactive hyperplasia. PMID- 26804120 TI - Reduced-cost sparsity-exploiting algorithm for solving coupled-cluster equations. AB - We present an algorithm for reducing the computational work involved in coupled cluster (CC) calculations by sparsifying the amplitude correction within a CC amplitude update procedure. We provide a theoretical justification for this approach, which is based on the convergence theory of inexact Newton iterations. We demonstrate by numerical examples that, in the simplest case of the CCD equations, we can sparsify the amplitude correction by setting, on average, roughly 90% nonzero elements to zeros without a major effect on the convergence of the inexact Newton iterations. PMID- 26804119 TI - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with liver involvement. AB - BACKGROUND: We examined outcomes of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) combined with liver resection. METHODS: All patients undergoing CRS/HIPEC between 2007 and 2014 were retrospectively reviewed: patients who underwent synchronous liver resection (group 1) were compared with those who did not (group 2) in terms of perioperative and long-term results. RESULTS: Group 1 included 103 patients with colorectal cancer (CRC, n = 28), appendiceal cancer (n = 34), and other malignancies. Compared with group 2 (n = 166), group 1 had higher number of organs resected, increased intraoperative blood loss, and longer hospital stay (all P <= 0.004) but similar major morbidity (24.3% vs. 18.1%, P = 0.22) and perioperative mortality rates. Two patients from group 1 developed liver resection-related complications. A comparison between patients who underwent parenchymal liver resection (n = 42) and matched pairs from group 2 with similar extent of cytoreduction did not yield significant differences in morbidity/mortality. CRC patients from group 1 had poorer median overall survival (45.1 vs. 73.5 months from stage IV diagnosis, P = 0.009). CONCLUSIONS: Liver involvement denotes high peritoneal carcinomatosis burden, which often requires resection of multiple organs in order to achieve optimal cytoreduction. However, liver resection-related morbidity is low and overall morbidity/mortality rates are comparable to other extensive CRS/HIPEC procedures. J. Surg. Oncol. 2016;113:432-437. (c) 2016 Wiley Periodicals, Inc. PMID- 26804122 TI - Strategies for Transferring Mixtures of Organic Contaminants from Aquatic Environments into Bioassays. AB - Mixtures of organic contaminants are ubiquitous in the environment. Depending on their persistence and physicochemical properties, individual chemicals that make up the mixture partition and distribute within the environment and might then jointly elicit toxicological effects. For the assessment and monitoring of such mixtures, a variety of cell-based in vitro and low-complexity in vivo bioassays based on algae, daphnids or fish embryos are available. A very important and sometimes unrecognized challenge is how to combine sampling, extraction and dosing to transfer the mixtures from the environment into bioassays, while conserving (or re-establishing) their chemical composition at adjustable levels for concentration-effect assessment. This article outlines various strategies for quantifiable transfer from environmental samples including water, sediment, and biota into bioassays using total extraction or polymer-based passive sampling combined with either solvent spiking or passive dosing. PMID- 26804126 TI - Extension of the interacting quantum atoms (IQA) approach to B3LYP level density functional theory (DFT). AB - An interaction between two atoms, bonded or non-bonded, consists of interatomic contributions: electrostatic energy, exchange energy and electronic correlation energy. Together with the intra-atomic energy of an atom, these contributions are the basic components of the Interacting Quantum Atom (IQA) energy decomposition scheme. Here, we investigate IQA's proper use in conjunction with an explicit implementation of the B3LYP functional. The recovery of the total molecular energy from the IQA components is emphasised, for the first time. A systematic study of three model systems of biological relevance, N-methylacetamide (NMA), the doubly capped tripeptide GlyGlyGly and an alloxan dimer, shows the stabilization effect of B3LYP on most of the interatomic exchange energies (V) compared to their Hartree-Fock values. Diagrams of exchange energies versus interatomic distance show the clustering of interactions, one cluster for each 1,n (n = 1 to 6 where the atoms are separated by n - 1 bonds). The positioning of some V values outside their expected cluster marks interesting interactions. PMID- 26804127 TI - Thiacalixarene assembled heterotrinuclear lanthanide clusters comprising Tb(III) and Yb(III) enable f-f communication to enhance Yb(III)-centred luminescence. AB - A mixture of heterotrinuclear lanthanide cluster complexes, Tb3-xYbxTCAS2 (x = 1, 2), was obtained by mixing thiacalix[4]arene-p-tetrasulfonate (TCAS), Tb(III), and Yb(III), which shows enhanced Yb(III)-centred luminescence and shortened lifetime for Tb(III)-centred luminescence as compared to Yb3TCAS2 and Tb3TCAS2, indicating f-f communication, i.e., energy transfer from Tb(III) to Yb(III). PMID- 26804130 TI - Antidepressant use and work-related injuries. AB - BACKGROUND: Adverse effects of antidepressants are most common at the beginning of the treatment, but possible also later. We examined the association between antidepressant use and work-related injuries taking into account the duration of antidepressant use. METHOD: Antidepressant use and work-related injuries between 2000 and 2011 were measured among 66 238 employees (mean age 43.8 years, 80% female) using linkage to national records (the Finnish Public Sector study). We analysed data using time-dependent modelling with individuals as their own controls (self-controlled case-series design). RESULTS: In 2238 individuals who had used antidepressants and had a work-related injury during a mean follow-up of 7.8 years, no increase in the risk of injury was observed in the beginning of antidepressant treatment. However, an increased injury risk was seen after 3 months of treatment (rate ratio, compared with no recent antidepressant use, 1.27, 95% confidence interval 1.10-1.48). This was also the case among those who had used only selective serotonin reuptake inhibitors (n = 714; rate ratio 1.41, 95% confidence interval 1.08-1.83). CONCLUSIONS: Antidepressant use was not associated with an increased risk of work-related injury at the beginning of treatment. Post-hoc analyses of antidepressant trials are needed to determine whether long-term use of antidepressants increases the risk of work-related injury. PMID- 26804131 TI - Selective recognition of fluoride salts by vasarenes: a key role of a self assembled in situ dimeric entity via an exceptionally short [O-H-O](-) H-bond. AB - A self-assembled supramolecular dimeric entity via an exceptionally short (2.404 A) and strong (22.9 kcal mol(-1)) [O-H-O](-) hydrogen bond is the key to the special reactivity of vasarenes with fluoride salts. Vasarene is a self assembled, vase-shaped compound, obtained by the reaction between ninhydrin and phloroglucinol. Analogous compounds are prepared by replacing the phloroglucinol with other polyhydroxy aromatics. Vasarenes show special affinity towards compounds of the type M(+)F(-), where M being a large monovalent cation, producing ion-pair-vasarene adducts. The first step in the proposed mechanism is the dissociation of the M(+)F(-) salt releasing F(-) to the solution, which may provide an explanation as to why only MF salts, which include large monovalent cations, undergo this reaction. From a practical point of view, the ease of their preparation and their special affinity towards fluoride salts make vasarenes potential means for salt separation. The readily formed dimeric structure with the very short [O-H-O](-) negative charge-assisted H-bond (-CAHB) can also be further used as a model in theoretical studies of such systems and understanding their role in biological processes. PMID- 26804133 TI - beta-Lapachone Regulates the Transforming Growth Factor-beta-Smad Signaling Pathway Associated with Collagen Biosynthesis in Human Dermal Fibroblasts. AB - The transforming growth factor (TGF)-beta-Smad signaling pathway regulates collagen biosynthesis in human dermal fibroblasts. We found that beta-lapachone stimulated type I collagen expression in human dermal fibroblasts. In this study, we evaluated whether the beta-lapachone-induced upregulation of collagen biosynthesis in human dermal fibroblasts is associated with the TGF-beta-Smad signaling pathway. In cultured human dermal fibroblasts, both Smad 2 and Smad 3 (Smad 2/3) were phosphorylated by beta-lapachone treatment in a concentration dependent manner. SB431542, a specific inhibitor of TGF-beta receptor I kinase, inhibited the beta-lapachone-mediated Smad 2/3 phosphorylation and type I collagen expression, suggesting that beta-lapachone stimulates collagen production via the TGF-beta receptor I kinase-dependent pathway. beta-Lapachone did not increase TGF-beta1 synthesis in human dermal fibroblasts, suggesting that the molecular mechanism of beta-lapachone for the upregulation of collagen synthesis is due to the extracellular regulation of availability and activities of TGF-beta. This study provides new insights into the role of beta-lapachone in collagen synthesis in human dermal fibroblasts and suggests that beta-lapachone can be used as a pharmacological tool to study collagen homeostasis associated with TGF-beta-Smad signaling. PMID- 26804132 TI - Meristem maintenance, auxin, jasmonic and abscisic acid pathways as a mechanism for phenotypic plasticity in Antirrhinum majus. AB - Plants grow under climatic changing conditions that cause modifications in vegetative and reproductive development. The degree of changes in organ development i.e. its phenotypic plasticity seems to be determined by the organ identity and the type of environmental cue. We used intraspecific competition and found that Antirrhinum majus behaves as a decoupled species for lateral organ size and number. Crowding causes decreases in leaf size and increased leaf number whereas floral size is robust and floral number is reduced. Genes involved in shoot apical meristem maintenance like ROA and HIRZ, cell cycle (CYCD3a; CYCD3b, HISTONE H4) or organ polarity (GRAM) were not significantly downregulated under crowding conditions. A transcriptomic analysis of inflorescence meristems showed Gene Ontology enriched pathways upregulated including Jasmonic and Abscisic acid synthesis and or signalling. Genes involved in auxin synthesis such as AmTAR2 and signalling AmANT were not affected by crowding. In contrast, AmJAZ1, AmMYB21, AmOPCL1 and AmABA2 were significantly upregulated. Our work provides a mechanistic working hypothesis where a robust SAM and stable auxin signalling enables a homogeneous floral size while changes in JA and ABA signalling maybe responsible for the decreased leaf size and floral number. PMID- 26804134 TI - Serotonin 5-HT2B Receptor-Stimulated DNA Synthesis and Proliferation Are Mediated by Autocrine Secretion of Transforming Growth Factor-alpha in Primary Cultures of Adult Rat Hepatocytes. AB - The mechanism of serotonin 5-HT2 receptor subtype-stimulated DNA synthesis and proliferation was investigated in primary cultures of adult rat hepatocytes to elucidate the intracellular signal transduction pathways. DNA synthesis and proliferation were detected in hepatocyte parenchymal cells grown in serum-free, defined medium containing 5-HT (10(-6) M) or the selective 5-HT2B receptor agonist BW723C86 (10(-6) M). In addition, exogenous transforming growth factor (TGF)-alpha (1.0 ng/mL) significantly increased hepatocyte DNA synthesis and proliferation, which reached plateau after 4 h of culture. Use of blocking monoclonal antibodies demonstrated that TGF-alpha, but not insulin-like growth factor-I, was involved in hepatocyte proliferation mediated by 5-HT or BW723C86. TGF-alpha levels in the culture medium increased significantly versus baseline within 5 min in response to 5-HT (10(-6) M) or BW723C86 (10(-6) M), and the maximum TGF-alpha level (30 pg/mL) was reached 10 min after 5-HT or BW723C86 stimulation. Secretion of TGF-alpha into the culture medium was inhibited by addition of the selective phospholipase C (PLC) inhibitor, U-73122 (10(-6) M), or somatostatin (10(-7) M). These results indicate that the proliferative mechanism of action of 5-HT is mediated mainly through a 5-HT2B receptor/Gq/PLC-stimulated increase in autocrine secretion of TGF-alpha from primary cultured hepatocytes. PMID- 26804136 TI - Growing sensitivity of maize to water scarcity under climate change. AB - Climate change can reduce crop yields and thereby threaten food security. The current measures used to adapt to climate change involve avoiding crops yield decrease, however, the limitations of such measures due to water and other resources scarcity have not been well understood. Here, we quantify how the sensitivity of maize to water availability has increased because of the shift toward longer-maturing varieties during last three decades in the Chinese Maize Belt (CMB). We report that modern, longer-maturing varieties have extended the growing period by an average of 8 days and have significantly offset the negative impacts of climate change on yield. However, the sensitivity of maize production to water has increased: maize yield across the CMB was 5% lower with rainfed than with irrigated maize in the 1980s and was 10% lower (and even >20% lower in some areas) in the 2000s because of both warming and the increased requirement for water by the longer-maturing varieties. Of the maize area in China, 40% now fails to receive the precipitation required to attain the full yield potential. Opportunities for water saving in maize systems exist, but water scarcity in China remains a serious problem. PMID- 26804137 TI - Mutation-induced perturbation of the special pair P840 in the homodimeric reaction center in green sulfur bacteria. AB - Homodimeric photosynthetic reaction centers (RCs) in green sulfur bacteria and heliobacteria are functional homologs of Photosystem (PS) I in oxygenic phototrophs. They show unique features in their electron transfer reactions; however, detailed structural information has not been available so far. We mutated PscA-Leu688 and PscA-Val689 to cysteine residues in the green sulfur bacterium Chlorobaculum tepidum; these residues were predicted to interact with the special pair P840, based on sequence comparison with PS I. Spectroelectrochemical measurements showed that the L688C and V689C mutations altered a near-infrared difference spectrum upon P840 oxidation, as well as the redox potential of P840. Light-induced Fourier transform infrared difference measurements showed that the L688C mutation induced a differential signal of the S-H stretching vibration in the P840(+)/P840 spectrum, as reported in P800(+)/P800 difference spectrum in a heliobacterial RC. Spectral changes in the 13(1)-keto C=O region, caused by both mutations, revealed corresponding changes in the electronic structure of P840 and in the hydrogen-bonding interaction at the 13(1)-keto C=O group. These results suggest that there is a common spatial configuration around the special pair sites among type 1 RCs. The data also provided evidence that P840 has a symmetric electronic structure, as expected from a homodimeric RC. PMID- 26804138 TI - Switchable graphene-substrate coupling through formation/dissolution of an intercalated Ni-carbide layer. AB - Control over the film-substrate interaction is key to the exploitation of graphene's unique electronic properties. Typically, a buffer layer is irreversibly intercalated "from above" to ensure decoupling. For graphene/Ni(111) we instead tune the film interaction "from below". By temperature controlling the formation/dissolution of a carbide layer under rotated graphene domains, we reversibly switch graphene's electronic structure from semi-metallic to metallic. Our results are relevant for the design of controllable graphene/metal interfaces in functional devices. PMID- 26804139 TI - Histopathological comparison of the onset of peri-implantitis and periodontitis in rats. AB - BACKGROUND AND OBJECTIVE: There are a few experimental models that clearly describe the pathological differences in tissue destruction between periodontitis and peri-implantitis. We recently reported that the formation of immune complexes accelerates site-specific loss of attachment and alveolar bone resorption when an antigen is topically applied in the gingival sulcus of an immunized rat. We applied this model to the peri-implant tissues and compared peri-implant destruction to periodontitis without using a ligature. MATERIAL AND METHODS: Twenty-five rats were used in this study and were divided into five groups. Implantation was performed immediately after extraction of right first molars in rats. The left first molars were left untreated to be examined as natural teeth. The immunized group consisted of rats that had received intraperitoneal lipopolysaccharide (LPS), whereas the nonimmunized group received only phosphate buffered saline (PBS). The untreated baseline group received only implantation. After intraperitoneal booster injection, half of each group received topical application of LPS in the palatal gingival sulcus daily for 3 days. The other half of the groups received PBS. Histopathological and histometrical findings were observed with hematoxylin and eosin staining, collagen fibers were observed with Azan staining, and formation of immune complexes was immunohistologically evaluated by C1qB expression. RESULT: Peri-implant tissue destruction was greater in the immunized and LPS-applied groups than in the other groups. No periodontal destruction was observed. Formation of immune complexes was observed in the junctional epithelium and adjacent connective tissue in the immunized groups. CONCLUSION: Antigen-induced peri-implant tissue destruction occurs faster than periodontal tissue destruction. PMID- 26804140 TI - Electropolymerization on wireless electrodes towards conducting polymer microfibre networks. AB - Conducting polymers can be easily obtained by electrochemical oxidation of aromatic monomers on an electrode surface as a film state. To prepare conducting polymer fibres by electropolymerization, templates such as porous membranes are necessary in the conventional methods. Here we report the electropolymerization of 3,4-ethylenedioxythiophene and its derivatives by alternating current (AC) bipolar electrolysis. Poly(3,4-ethylenedioxythiophene) (PEDOT) derivatives were found to propagate as a fibre form from the ends of Au wires used as bipolar electrodes (BPEs) parallel to an external electric field, without the use of templates. The effects of applied frequency and of the solvent on the morphology, growth rate and degree of branching of these PEDOT fibres were investigated. In addition, a chain-growth model for the formation of conductive material networks was also demonstrated. PMID- 26804141 TI - An Empirical Comparison Of The Similarity Of Principal Component, Image, And Factor Patterns. AB - Factor analysis, image component analysis, and principal component analysis are three methods that have been employed for the same purpose. Factor analysis was traditionally viewed as the preferred method, with other methods serving as computationally easier approximations. Recently attention has been focused on theoretical problems with the factor analysis model such as the factor indeterminacy issue. In order to assess the degree of similarity between the results produced by each of the three methods, the patterns produced by maximum likelihood factor analysis, rescaled image analysis, and principal component analysis are compared for nine data sets. Two different comparisons are considered: a direct loading-by-loading comparison of the patterns, and a summary statistic defined on the matrix of differences between patterns. Comparisons are made for the patterns in both orthogonal and oblique rotational positions, and a position of maximum similarity is achieved by an orthogonal procrustes rotation. The patterns produced by each of the three methods were remarkably similar. Image component analysis and maximum likelihood factor analysis generally produced the most similar results and principal component analysis and maximum likelihood factor analysis generally produced the most dissimilar results. Differences generally occurred in the last factor extracted, possibly because too many factors had been extracted. PMID- 26804142 TI - Multidimensional Scaling Of The Molar Physical Environment. AB - Two experiments were carried out in order to make tests of several hypotheses concerning perceptions of the molar physical environment. In the first, subjects did multiple category sorts of pictures of environments from three different functional orientations (what is done in or to the environment). In the second, subjects made similarity judgments of all pairs of the same pictures. Data from both experiments were analyzed by INDSCAL and MDSCAL and the resulting multidimensional stimulus spaces compared across conditions, experiments, and analysis methods. It was found that as functional orientations change (Expt. I), stimulus structures and dimensional interpretations of those structures remain invariant, while individual saliences of those dimensions change. Dimensions of naturalness and scale predominated in both experiments, and dimensional and stimulus structures were highly similar across judgment methods. INDSCAL and MDSCAL solutions were highly similar, but INDSCAL solutions were easier to interpret without rotation, while MDSCAL tended to extract fewer dimensions and to fit better with the original data. In the second experiment dimensional saliences were related to subjects' background characteristics and clusters of subjects were characterized according to differences in dimensional saliences. PMID- 26804143 TI - A Study Of A Measure Of Sampling Adequacy For Factor-Analytic Correlation Matrices. AB - Kaiser's Measure of Sampling Adequacy (MSA) for factor-analytic correlation matrices is studied for several levels each of p, the number of variables, q, the number of factors, and rfl, the root-mean-square off-diagonal correlation. The major influence for MSA is p, in agreement with theory; the joint main effect influences of p, q, and rfl to the total SSs remains greater than 84% under various choices of the levels of p, q, and rfl. PMID- 26804144 TI - Effect Of Chronic Exercise On The Multivariate Relationships Between Selected Biochemical And Personality Variables. PMID- 26804145 TI - An Examination Of Some Factors Related To Using Different Minkowski Models In Non Metric Multidimensional Scaling. AB - Great interest in non-metric multidimensional scaling has resulted in a number of computer programs to derive solutions. This study examined the effect upon stress of data generated under five metrics and recovered under all five metrics. MDSCAL 5M. TORSCA-9, and POLYCON-II were used to analyse these data. POLYCON-II was the most accurate, although none of the programs was highly successful. In most cases recovery with the Euclidian metric provided, if not the best, very close to the best recovery regardless of the true metric. This study also raised the question of the advisability of using different metric models in nonmetric multidimensional scaling and found that even very different Minkowski metrics are quite similar in the way they rank order dissimilarities. PMID- 26804146 TI - Canonical Analysis And Predictor Selection. AB - This paper addresses theoretical and practical issues in the use of canonical analysis for prediction. A major objection to canonical prediction has been that the variates that are predicted are of low utility and do not reflect practical concerns. This problem may be overcome by a stepwise approach to the selection of predictor variables such that those predictors which predict the desired criterion are retained. In addition, canonical analysis may provide a solution to the problem of multidimensional criteria. PMID- 26804147 TI - Method Variance, Inadequate Constructs, Or Things That Go Bump In The Night? AB - Jackson's (1975) revised method for multimethod factor analysis and his critique of Golding and Seidman's (1974) similar "two step principal components" procedure are critically examined. While Jackson's revised method is more empirically defensible, the conceptual assumptions upon which it is based may not be warranted, and his critique of the Golding-Seidman method may be misleading. It is argued that "method variance" is properly viewed as a hidden facet of nomologicals underlying a construct, and that multimethod investigations that fail to specify the nomological, assumptions surrounding particular trait-method units are conceptually and empirically unsound. PMID- 26804148 TI - Distinguishing Trait And Method Variance In Multitrait-Multimethod Matrices: A Reply To Golding. AB - Some observations are provided regarding certain techniques for the evaluation of the problem posed by Campbell and Fiske, that of convergent and discriminant validation. A recent proposal by Golding and Seidman (1974) for the evaluation of multitrait-multimethod matrices is found to be inadequate for this problem because it (a) is inconsistent with the Campbell-Fiske requirements of testing traits as separate units; (b) confounds trait and method variance; (c) offers no empirically defensible definition or technique for isolating method variance; and (d) yields absurd results when applied to a matrix highly consistent with Campbell-Fiske criteria for convergent and discriminant validity. Golding's (1976) conjecture that factors designated as trait factors contained method variance in Jackson's (1975) reformulated multimethod factor analysis logically was found to be based on an implicit redefinition of terms by Golding, and could not be verified empirically. It was suggested that methods for evaluating trait and method variance need not await a fully developed nomological network for application, but might proceed through an interplay between inductive generalization and theory. PMID- 26804149 TI - Analysis Of Quasi-Experimental Time-Series Designs. AB - Multivariate procedures, based on the general linear hypothesis, are outlined for inferring treatment effects in quasi-experimental time-series designs. These procedures, which take into account the dependent nature of the data obtained in time-series experiments and which require comparing the fitted regression curves for the pre-treatment and post-treatment observations, provide exact tests of significance for the various hypotheses of interest. PMID- 26804150 TI - Prognostic factors in alveolar soft part sarcoma: A SEER analysis. AB - OBJECTIVES: We reviewed the clinical characteristics and outcomes of patients treated for alveolar soft part sarcoma (ASPS) and analyzed the effect of surgery for patients presenting with and without metastatic disease (DM). METHODS: The SEER Registry was queried for patients with ASPS from 1973-2012. The Kaplan-Meier estimate and Cox proportional hazards were used to analyze survival outcomes and risk variables. RESULTS: Among 251 patients, 43% had DM and 67% locoregional disease (LR) on presentation. The 5-year overall survival (OS) for all patients was 56% (82% and 27% for LR and DM, respectively). Multivariate analysis identified older age (hazard ratio [HR] = 1.03 per year, P < 0.001), tumor size >10 cm (HR = 2.76, P = 0.013), DM at diagnosis (HR = 3.79, P < 0.001), and truncal primary site (HR = 1.63, P = 0.035) as independent factors predicting worse OS. For LR patients, surgery plus radiotherapy (RT) resulted in better OS compared to surgery alone P = 0.014. For DM patients, primary site surgery significantly improved survival (P < 0.001). CONCLUSION: ASPS presents with high metastasis rate but has a relatively indolent clinical course and a favorable prognosis with prolonged survival. Aggressive treatment using adjuvant RT with surgery is indicated in patients with LR disease and surgery is indicated in patients presenting with DM. J. Surg. Oncol. 2016;113:581-586. (c) 2016 Wiley Periodicals, Inc. PMID- 26804151 TI - A method for predicting protein conformational pathways by using molecular dynamics simulations guided by difference distance matrices. AB - Here, an efficient method that predicts natural transition pathways between two endpoint states of an allosteric protein has been proposed. This method helps create structures that bridge these endpoints through multiple iterative and unbiased molecular dynamics simulations with explicit water. Difference distance matrices provide an approach for identifying states involving concerted slow motion. A series of structures are readily generated along the transition pathways of adenylate kinase. Predicted structures may be useful for an initial pathway to evaluate free energy landscapes via umbrella sampling and chain-of states methods. (c) 2016 Wiley Periodicals, Inc. PMID- 26804157 TI - ZnO nanorod/porous silicon nanowire hybrid structures as highly-sensitive NO2 gas sensors at room temperature. AB - ZnO nanorod/porous silicon nanowire (ZnO/PSiNW) hybrids with three different structures as highly sensitive NO2 gas sensors were obtained. PSiNWs were first synthesized by metal-assisted chemical etching, and then seeded in three different ways. After that ZnO nanorods were grown on the seeded surface of PSiNWs using a hydrothermal procedure. ZnO/PSiNW hybrids showed excellent gas sensing performance for various NO2 concentrations (5-50 ppm) at room temperature, and the electrical resistance change rate reached as high as 35.1% when responding to 50 ppm NO2. The distinct enhancement was mainly attributed to the faster carrier transportation after combination, the increase in gas sensing areas and the oxygen vacancy (VO) concentration. Moreover, the p-type gas sensing behavior was explained by the gas sensing mechanism and the effect of VO concentration on gas sensing properties was also discussed concerning the photoluminescence (PL) spectra performance. PMID- 26804159 TI - Coexistence of Aflatoxicosis with Protein Malnutrition Worsens Hepatic Oxidative Damage in Rats. AB - To investigate the effects of the coexistence of aflatoxin B1 (AFB1) and protein malnutrition in rat liver, weanling rats were fed either normal protein diet (20% protein), low-protein (PEM) diet (5%), normal protein diet + 40 ppb AFB1, or low protein diet + 40 ppb AFB1. After 8 weeks, biomarkers of hepatic functions and oxidative stress, caspase-3 activity, and tumor suppressor protein 53 (p53) were determined spectrophotometrically. Randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) was employed to determine genomic alterations among the groups. Coexistence of aflatoxicosis and PEM significantly decreased glutathione, glutathione-S-transferase, glutathione peroxidase, and superoxide dismutase, while it increased peroxidase and catalase. RAPD-PCR showed genomic alterations that were associated with significant increases in p53 level and caspase-3 activity in rats fed PEM diet + AFB1. In conclusion, the coexistence of aflatoxicosis and protein malnutrition induced oxidative stress with concomitant genomic alterations in the liver of weanling rats. PMID- 26804160 TI - Photoresponsive self-healing supramolecular hydrogels for light-induced release of DNA and doxorubicin. AB - An azobenzene-containing cyclic dipeptide PAP-DKP-Lys is a photoresponsive low-MW hydrogelator. The gelation process can be triggered with temperature, pH, light, and ionic strength. The resulting self-healing gels can encapsulate dsDNA or an anticancer drug doxorubicin, and release them in a light-dependent manner. PMID- 26804161 TI - Beyond the Sterility of a Distinct African Bioethics: Addressing the Conceptual Bioethics Lag in Africa. AB - In the current debate on the future of bioethics in Africa, several authors have argued for a distinct communitarian African bioethics that can counter the dominancy of Western atomistic principlism in contemporary bioethics. In this article I examine this rather contentious argument and evaluate its validity and viability. Firstly, I trace the contextual origins of contemporary bioethics and highlight the rise and dominance of principlism. I particularly note that principlism was premised on a content-thin notion of the common morality that is in need of enrichment. I also contend that bioethics is essentially two dimensional, being both conceptual and empirical, and indicate the lag in Africa with regard to conceptual bioethics. I then appeal for authentic engagement by 1) African health care professionals, 2) African health care training institutions, 3) Africa's bioethics development partners, and 4) African bioethicists and philosophers, towards addressing this critical lag. I underline the need to maintain the essential universality of bioethics as a discipline. I particularly argue against the pursuit of a distinct African bioethics, as it appears to be rooted in sterile African ethno-philosophy. Rather, African bioethicists and philosophers would do well to elucidate the universalisability of insights from traditional African thought, for the benefit of bioethics as a whole. Thus we must engage beyond the sterility of a distinct African bioethics - authentically reflecting on the essentially universal contemporary bioethical concerns - to effectively articulate a viable trajectory for bioethics in Africa. PMID- 26804162 TI - Engineering and comparison of non-natural pathways for microbial phenol production. AB - The non-renewable petrochemical phenol is used as a precursor to produce numerous fine and commodity chemicals, including various pharmaceuticals and phenolic resins. Microbial phenol biosynthesis has previously been established, stemming from endogenous tyrosine via tyrosine phenol lyase (TPL). TPL, however, suffers from feedback inhibition and equilibrium limitations, both of which contribute to reduced flux through the overall pathway. To address these limitations, two novel and non-natural phenol biosynthesis pathways, both stemming instead from chorismate, were constructed and comparatively evaluated. The first proceeds to phenol in one heterologous step via the intermediate p-hydroxybenzoic acid, while the second involves two heterologous steps and the associated intermediates isochorismate and salicylate. Maximum phenol titers achieved via these two alternative pathways reached as high as 377 +/- 14 and 259 +/- 31 mg/L in batch shake flask cultures, respectively. In contrast, under analogous conditions, phenol production via the established TPL-dependent route reached 377 +/- 23 mg/L, which approaches the maximum achievable output reported to date under batch conditions. Additional strain development and optimization of relevant culture conditions with respect to each individual pathway is ultimately expected to result in further improved phenol production. Biotechnol. Bioeng. 2016;113: 1745 1754. (c) 2016 Wiley Periodicals, Inc. PMID- 26804163 TI - VEGF-A acts via neuropilin-1 to enhance epidermal cancer stem cell survival and formation of aggressive and highly vascularized tumors. AB - We identify a limited subpopulation of epidermal cancer stem cells (ECS cells), in squamous cell carcinoma, that form rapidly growing, invasive and highly vascularized tumors, as compared with non-stem cancer cells. These ECS cells grow as non-attached spheroids, and display enhanced migration and invasion. We show that ECS cell-produced vascular endothelial growth factor (VEGF)-A is required for the maintenance of this phenotype, as knockdown of VEGF-A gene expression or treatment with VEGF-A-inactivating antibody reduces these responses. In addition, treatment with bevacizumab reduces tumor vascularity and growth. Surprisingly, the classical mechanism of VEGF-A action via interaction with VEGF receptors does not mediate these events, as these cells lack VEGFR1 and VEGFR2. Instead, VEGF-A acts via the neuropilin-1 (NRP-1) co-receptor. Knockdown of NRP-1 inhibits ECS cell spheroid formation, invasion and migration, and attenuates tumor formation. These studies suggest that VEGF-A acts via interaction with NRP-1 to trigger intracellular events leading to ECS cell survival and formation of aggressive, invasive and highly vascularized tumors. PMID- 26804165 TI - GEP oncogene promotes cell proliferation through YAP activation in ovarian cancer. AB - G-protein-coupled receptors (GPCRs) and their ligands function in the progression of human malignancies. Galpha12 and Galpha13, encoded by GNA12 and GNA13, respectively, are referred to as the GEP oncogene and are implicated in tumor progression. However, the molecular mechanisms by which Galpha12/13 activation promotes cancer progression are not fully elucidated. Here, we demonstrate elevated expression of Galpha12/13 in human ovarian cancer tissues. Galpha12/13 activation did not promote cellular migration in the ovarian cancer cell lines examined. Rather, Galpha12/13 activation promoted cell growth. We used a synthetic biology approach using chimeric G proteins and GPCRs activated solely by artificial ligands to selectively trigger signaling pathways downstream of specific G proteins. We found that Galpha12/13 promotes proliferation of ovarian cancer cells by activating the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway. Furthermore, we reveal that inhibition of YAP by short hairpin RNA or a specific inhibitor prevented the growth of ovarian cancer cells. Therefore, YAP may be a suitable therapeutic target in ovarian cancer. PMID- 26804166 TI - High expression of connective tissue growth factor accelerates dissemination of leukaemia. AB - To improve treatment of acute lymphoblastic leukaemia (ALL), a better understanding of disease development is needed to tailor new therapies. Connective tissue growth factor (CTGF/CCN2) is highly expressed in leukaemia cells from the majority of paediatric patients with B-lineage ALL (pre-B ALL). CTGF is a matricellular protein and plays a role in aggressive cancers. Here we have genetically engineered leukaemia cells to modulate CTGF expression levels. Elevated CTGF levels accelerated disease dissemination and reduced survival in NOD/SCID mice. In vitro studies showed that CTGF protein induces stromal cell proliferation, promotes adhesion of leukaemia cells to stromal cells and leads to overexpression of genes associated with cell cycle and synthesis of extracellular matrix (ECM). Corresponding data from our leukaemia xenograft models demonstrated that CTGF leads to increased proliferation of non-leukaemia cells and deposition of ECM in the bone marrow. We document for the first time a functional role of CTGF in altering disease progression in a lymphoid malignancy. The findings provide support for targeting the bone marrow microenvironment in aggressive forms of leukaemia. PMID- 26804167 TI - The fibronectin/alpha3beta1 integrin axis serves as molecular basis for keratinocyte invasion induced by betaHPV. AB - Organ-transplant-recipients exhibit cancerization of the skin from which multiple human papillomavirus (HPV)-positive squamous cell carcinomas (SCCs) arise. However, the molecular basis for HPV-induced invasion of skin keratinocytes is not known. We generated a transgenic mouse model expressing the E7 oncoprotein of HPV8 in the murine epidermis under the control of the keratin-14 promoter and showed that E7 is carcinogenic in mice. We further showed that both, the E7 expressing keratinocyte and mesenchymal components of the extracellular matrix as critical in eliciting the invasive behavior. E7 expression in basal keratinocytes, grown on fibronectin, led to epithelial-mesenchymal transition mediated by a cadherin switch. E7-positive keratinocytes displayed enhanced EDA fibronectin expression and secretion and stimulated dermal fibroblasts to express EDA-fibronectin. Deposition of fibronectin was also detected in the peritumoral stroma of HPV8-positive skin SCC. When grown on fibronectin, E7-positive keratinocytes, in particular stem cell-like cells, exhibited increased cell surface levels of the alpha3-integrin chain. Functional blocking confirmed alpha3 as a critical molecule sufficient to induce E7-mediated invasion. This mechanistic link is further supported by expression of an E7-mutant, impaired in targeting alpha3 to the cell surface. These findings highlight the importance of epithelial-extracellular matrix interaction required for keratinocyte invasion and provide further mechanistic evidence for a role of HPV in skin carcinogenesis. PMID- 26804164 TI - Epigenomic regulation of oncogenesis by chromatin remodeling. AB - Disruption of the intricate gene expression program represents one of major driving factors for the development, progression and maintenance of human cancer, and is often associated with acquired therapeutic resistance. At the molecular level, cancerous phenotypes are the outcome of cellular functions of critical genes, regulatory interactions of histones and chromatin remodeling complexes in response to dynamic and persistent upstream signals. A large body of genetic and biochemical evidence suggests that the chromatin remodelers integrate the extracellular and cytoplasmic signals to control gene activity. Consequently, widespread dysregulation of chromatin remodelers and the resulting inappropriate expression of regulatory genes, together, lead to oncogenesis. We summarize the recent developments and current state of the dysregulation of the chromatin remodeling components as the driving mechanism underlying the growth and progression of human tumors. Because chromatin remodelers, modifying enzymes and protein-protein interactions participate in interpreting the epigenetic code, selective chromatin remodelers and bromodomains have emerged as new frontiers for pharmacological intervention to develop future anti-cancer strategies to be used either as single-agent or in combination therapies with chemotherapeutics or radiotherapy. PMID- 26804169 TI - HTLV-1 bZIP factor protein targets the Rb/E2F-1 pathway to promote proliferation and apoptosis of primary CD4(+) T cells. AB - Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that induces a fatal T-cell malignancy, adult T-cell leukemia (ATL). Among several regulatory/accessory genes in HTLV-1, HTLV-1 bZIP factor (HBZ) is the only viral gene constitutively expressed in infected cells. Our previous study showed that HBZ functions in two different molecular forms, HBZ protein and HBZ RNA. In this study, we show that HBZ protein targets retinoblastoma protein (Rb), which is a critical tumor suppressor in many types of cancers. HBZ protein interacts with the Rb/E2F-1 complex and activates the transcription of E2F-target genes associated with cell cycle progression and apoptosis. Mouse primary CD4(+) T cells transduced with HBZ show accelerated G1/S transition and apoptosis, and importantly, T cells from HBZ transgenic (HBZ-Tg) mice also demonstrate enhanced cell proliferation and apoptosis. To evaluate the functions of HBZ protein alone in vivo, we generated a new transgenic mouse strain that expresses HBZ mRNA altered by silent mutations but encoding intact protein. In these mice, the numbers of effector/memory and Foxp3(+) T cells were increased, and genes associated with proliferation and apoptosis were upregulated. This study shows that HBZ protein promotes cell proliferation and apoptosis in primary CD4(+) T cells through activation of the Rb/E2F pathway, and that HBZ protein also confers onto CD4(+) T-cell immunophenotype similar to those of ATL cells, suggesting that HBZ protein has important roles in dysregulation of CD4(+) T cells infected with HTLV-1. PMID- 26804168 TI - Inhibition of FOXC2 restores epithelial phenotype and drug sensitivity in prostate cancer cells with stem-cell properties. AB - Advanced prostate adenocarcinomas enriched in stem-cell features, as well as variant androgen receptor (AR)-negative neuroendocrine (NE)/small-cell prostate cancers are difficult to treat, and account for up to 30% of prostate cancer related deaths every year. While existing therapies for prostate cancer such as androgen deprivation therapy (ADT), destroy the bulk of the AR-positive cells within the tumor, eradicating this population eventually leads to castration resistance, owing to the continued survival of AR-/lo stem-like cells. In this study, we identified a critical nexus between p38MAPK signaling, and the transcription factor Forkhead Box Protein C2 (FOXC2) known to promote cancer stem cells and metastasis. We demonstrate that prostate cancer cells that are insensitive to ADT, as well as high-grade/NE prostate tumors, are characterized by elevated FOXC2, and that targeting FOXC2 using a well-tolerated p38 inhibitor restores epithelial attributes and ADT-sensitivity, and reduces the shedding of circulating tumor cells in vivo with significant shrinkage in the tumor mass. This study thus specifies a tangible mechanism to target the AR-/lo population of prostate cancer cells with stem-cell properties. PMID- 26804170 TI - A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation. AB - Bruton's tyrosine kinase (BTK) is essential for B-cell proliferation/differentiation and it is generally believed that its expression and function are limited to bone marrow-derived cells. Here, we report the identification and characterization of p65BTK, a novel isoform abundantly expressed in colon carcinoma cell lines and tumour tissue samples. p65BTK protein is expressed, through heterogeneous nuclear ribonucleoprotein K (hnRNPK) dependent and internal ribosome entry site-driven translation, from a transcript containing an alternative first exon in the 5'-untranslated region, and is post transcriptionally regulated, via hnRNPK, by the mitogen-activated protein kinase (MAPK) pathway. p65BTK is endowed with strong transforming activity that depends on active signal-regulated protein kinases-1/2 (ERK1/2) and its inhibition abolishes RAS transforming activity. Accordingly, p65BTK overexpression in colon cancer tissues correlates with ERK1/2 activation. Moreover, p65BTK inhibition affects growth and survival of colon cancer cells. Our data reveal that BTK, via p65BTK expression, is a novel and powerful oncogene acting downstream of the RAS/MAPK pathway and suggest that its targeting may be a promising therapeutic approach. PMID- 26804171 TI - WASF3 provides the conduit to facilitate invasion and metastasis in breast cancer cells through HER2/HER3 signaling. AB - The WASF3 gene is overexpressed in high-grade breast cancer and promotes invasion and metastasis, but does not affect proliferation. The HER2/ERBB2/NEU gene is also frequently overexpressed in breast cancer, and has been shown to promote invasion and metastasis in these tumors. Here, we show that WASF3 is present in the HER2 immunocomplex and suppression of WASF3 function leads to suppression of invasion even in the presence of HER2 expression. Overexpression of both HER2 and WASF3 in non-metastatic MCF7 breast cancer cells promotes invasion and metastasis more significantly than either gene alone. HER2 forms homodimers as well as heterodimers with other HER family members and we now show that the ability of WASF3 to promote invasion is highly dependent on the HER2/HER3 heterodimer. The engagement of WASF3 with the HER2/HER3 complex facilitates its phospho-activation and transcriptional upregulation, which is facilitated by HER2/HER3 activation of JAK/STAT signaling. In breast cancer cells overexpressing HER2, therefore, WASF3 is specifically required to facilitate the invasion/metastasis response. Targeting WASF3, therefore, could be a potential therapeutic approach to suppress metastasis of HER2-overexpressing breast tumors. PMID- 26804172 TI - Adenomatous polyposis coli (APC) regulates miR17-92 cluster through beta-catenin pathway in colorectal cancer. AB - Adenomatous polyposis coli (APC) mutation is the most common genetic change in sporadic colorectal cancer (CRC). Although deregulations of miRNAs have been frequently reported in this malignancy, APC-regulated miRNAs have not been extensively documented. Here, by using an APC-inducible cell line and array analysis, we identified a total of 26 deregulated miRNAs. Among them, members of miR-17-92 cluster were dramatically inhibited by APC and induced by enforced expression of beta-catenin. Furthermore, we demonstrate that activated beta catenin resulted from APC loss binds to and activates the miR-17-92 promoter. Notably, enforced expression of miR-19a overrides APC tumor suppressor activity, and knockdown of miR-19a in cancer cells with compromised APC function reduced their aggressive features in vitro. Finally, we observed that expression of miR 19a significantly correlates with beta-catenin levels in colorectal cancer specimens, and it is associated to the aggressive stage of tumor progression. Thus, our study reveals that miR-17-92 cluster is directly regulated by APC/beta catenin pathway and could be a potential therapeutic target in colon cancers with aberrant APC/beta-catenin signaling. PMID- 26804173 TI - Therapeutic targeting of tetraspanin8 in epithelial ovarian cancer invasion and metastasis. AB - Epithelial ovarian cancer (EOC) invasion and metastasis are complex phenomena that result from the coordinated action of many metastatic regulators and must be overcome to improve clinical outcomes for patients with these cancers. The identification of novel therapeutic targets is critical because of the limited success of current treatment regimens, particularly in advanced-stage ovarian cancers. In this study, we found that tetraspanin 8 (TSPAN8) is overexpressed in about 52% (14/27) of EOC tissues and correlates with poor survival. Using small interfering RNA-mediated TSPAN8 knockdown and a competition assay with purified TSPAN8 large extracellular loop (TSPAN8-LEL) protein, we identified TSPAN8-LEL as a key regulator of EOC cell invasion. Furthermore, monotherapy with TSPAN8 blocking antibody we developed shows that antibody-based modulation of TSPAN8-LEL can significantly reduce the incidence of EOC metastasis without severe toxicity in vivo. Finally, we demonstrated that the TSPAN8-blocking antibody promotes the internalization and concomitant downregulation of cell surface TSPAN8. Collectively, our data suggest TSPAN8 as a potential novel therapeutic target in EOCs and antibody targeting of TSPAN8 as an effective strategy for inhibiting invasion and metastasis of TSPAN8-expressing EOCs. PMID- 26804174 TI - Splicing regulator SLU7 preserves survival of hepatocellular carcinoma cells and other solid tumors via oncogenic miR-17-92 cluster expression. AB - Resisting death is a central hallmark of cancer cells. Tumors rely on a number of genetic mechanisms to avoid apoptosis, and alterations in mRNA alternative splicing are increasingly recognized to have a role in tumorigenesis. In this study, we identify the splicing regulator SLU7 as an essential factor for the preservation of hepatocellular carcinoma (HCC) cells viability. Compared with hepatocytes, SLU7 expression is reduced in HCC cells; however, further SLU7 depletion triggered autophagy-related cellular apoptosis in association with the overproduction of reactive oxygen species. Remarkably, these responses were not observed in primary human hepatocytes or in the well-differentiated HepaRG cell line. Mechanistically, we demonstrate that SLU7 binds the C13orf25 primary transcript in which the polycistronic oncomir miR-17-92 cluster is encompassed, and is necessary for its processing and expression. SLU7 knockdown altered the splicing of the C13orf25 primary transcript, and markedly reduced the expression of its miR-17, miR-20 and miR-92a constituents. This led to the upregulation of CDKN1A (P21) and BCL2L11 (BIM) expression, two bona fide targets of the miR-17-92 cluster and recognized mediators of its pro-survival and tumorigenic activity. Interestingly, altered splicing of miR-17-92 and downregulation of miR-17 and miR 20 were not observed upon SLU7 knockdown in non-transformed hepatocytes, but was found in other (HeLa, H358) but not in all (Caco2) non-hepatic tumor cells. The functional relevance of miR-17-92 dysregulation upon SLU7 knockdown was established when oxidative stress, autophagy and apoptosis were reversed by co transfection of HCC cells with a miR-17 mimic. Together, these findings indicate that SLU7 is co-opted by HCC cells and other tumor cell types to maintain survival, and identify this splicing regulator as a new determinant for the expression of the oncogenic miR-17-92 cluster. This novel mechanism may be exploited for the development of antitumoral strategies in cancers displaying such SLU7-miR-17-92 crosstalk. PMID- 26804175 TI - Role of Runx2 in IGF-1Rbeta/Akt- and AMPK/Erk-dependent growth, survival and sensitivity towards metformin in breast cancer bone metastasis. AB - The mechanisms underlying reprogramming of growth factor signaling and metabolic pathways during bone metastasis of breast cancer are not clear. The Runt-related transcription factor (Runx2) regulates cell signaling during mammary epithelial morphogenesis and promotes invasion; therefore, we investigated its role in cell growth and metabolic signaling in bone-seeking breast cancer cells. We performed systemic inoculation of control or Runx2 knockdown invasive MDA-MB-231 cells in NOD/SCID mice, and compared parental and bone-derived variants for phenotypic and molecular alterations. The Runx2 knockdown showed early (0-2 weeks) inhibition of metastatic spread but late (4-6 weeks) outgrowth, suggesting Runx2-dependent bi phasic response and reprogramming of metastatic cells. The late-stage tumor outgrowth of bone-derived Runx2 knockdown cells was associated with increased insulin-like growth factor- 1Rbeta (IGF-1Rbeta) levels. Interestingly, glucose uptake and glycolysis were reduced in the bone-derived Runx2 knockdown cells that could be further reduced by extracellular-regulated protein kinase (Erk1/2) inhibition. Furthermore, the Runx2 knockdown cells displayed activation of AMP activated protein kinase (AMPKalpha), the sensor of cellular metabolism. Importantly, the Runx2 knockdown in bone-derived cells resulted in increased sensitivity to both Erk1/2 inhibition and AMPKalpha activation by PD184161 and metformin, respectively, despite increased IGF-1Rbeta and AMPKalpha levels. Our results reveal that Runx2 promotes metastatic spread of mammary tumor cells. The growth of late-stage tumor cells can be targeted by Runx2 knockdown in combination with Mek-Erk1/2 inhibition and metformin treatment. PMID- 26804176 TI - A novel association of neuropilin-1 and MUC1 in pancreatic ductal adenocarcinoma: role in induction of VEGF signaling and angiogenesis. AB - We report that Mucin1 (MUC1), a transmembrane glycoprotein that is overexpressed in >80% of pancreatic ductal adenocarcinoma (PDA), induced a pro-angiogenic tumor microenvironment by increasing the levels of neuropilin-1 (NRP1, a co-receptor of vascular endothelial growth factor (VEGF)) and its ligand VEGF. Expression of tumor-associated MUC1 (tMUC1) positively correlated with NRP1 levels in human and mouse PDA. Further, tMUC1hi PDA cells secreted high levels of VEGF and expressed high levels of VEGF receptor 2 (VEGFR2) and its phosphorylated forms as compared with tMUC1low/null PDA. This enabled the tMUC1hi/NRP1hi PDA cells to (a) induce endothelial cell tube formation, (b) generate long ectopic blood vessels and (c) enhance distant metastasis in a zebrafish xenograft model. Concurrently, the proteins associated with epithelial-to-mesenchymal transition, N-cadherin and Vimentin, were highly induced in these tMUC1/NRP1hi PDA cells. Hence, blocking signaling via the NRP1-VEGF axis significantly reduced tube formation, new vessel generation and metastasis induced by tMUC1hi PDA cells. Finally, we show that blocking the interaction between VEGF165 and NRP1 with a NRP1 antagonist significantly reduced VEGFR signaling and PDA tumor growth in vivo. Taken together, our data suggest a novel molecular mechanism by which tMUC1 may modulate NRP1-dependent VEGFR signaling in PDA cells. PMID- 26804177 TI - BET bromodomain inhibitors synergize with ATR inhibitors to induce DNA damage, apoptosis, senescence-associated secretory pathway and ER stress in Myc-induced lymphoma cells. AB - Inhibiting the bromodomain and extra-terminal (BET) domain family of epigenetic reader proteins has been shown to have potent anti-tumoral activity, which is commonly attributed to suppression of transcription. In this study, we show that two structurally distinct BET inhibitors (BETi) interfere with replication and cell cycle progression of murine Myc-induced lymphoma cells at sub-lethal concentrations when the transcriptome remains largely unaltered. This inhibition of replication coincides with a DNA-damage response and enhanced sensitivity to inhibitors of the upstream replication stress sensor ATR in vitro and in mouse models of B-cell lymphoma. Mechanistically, ATR and BETi combination therapy cause robust transcriptional changes of genes involved in cell death, senescence associated secretory pathway, NFkB signaling and ER stress. Our data reveal that BETi can potentiate the cell stress and death caused by ATR inhibitors. This suggests that ATRi can be used in combination therapies of lymphomas without the use of genotoxic drugs. PMID- 26804178 TI - Endoglin targeting inhibits tumor angiogenesis and metastatic spread in breast cancer. AB - Endoglin, a transforming growth factor-beta co-receptor, is highly expressed on angiogenic endothelial cells in solid tumors. Therefore, targeting endoglin is currently being explored in clinical trials for anti-angiogenic therapy. In this project, the redundancy between endoglin and vascular endothelial growth factor (VEGF) signaling in angiogenesis and the effects of targeting both pathways on breast cancer metastasis were explored. In patient samples, increased endoglin signaling after VEGF inhibition was observed. In vitro TRC105, an endoglin neutralizing antibody, increased VEGF signaling in endothelial cells. Moreover, combined targeting of the endoglin and VEGF pathway, with the VEGF receptor kinase inhibitor SU5416, increased antiangiogenic effects in vitro and in a zebrafish angiogenesis model. Next, in a mouse model for invasive lobular breast cancer, the effects of TRC105 and SU5416 on tumor growth and metastasis were explored. Although TRC105 and SU5416 decreased tumor vascular density, tumor volume was unaffected. Strikingly, in mice treated with TRC105, or TRC105 and SU5416 combined, a strong inhibition in the number of metastases was seen. Moreover, upon resection of the primary tumor, strong inhibition of metastatic spread by TRC105 was observed in an adjuvant setting. To confirm these data, we assessed the effects of endoglin-Fc (an endoglin ligand trap) on metastasis formation. Similar to treatment with TRC105 in the resection model, endoglin-Fc expressing tumors showed strong inhibition of distant metastases. These results show, for the first time, that targeting endoglin, either with neutralizing antibodies or a ligand trap, strongly inhibits metastatic spread of breast cancer in vivo. PMID- 26804179 TI - The contribution of inner and outer retinal photoreceptors to infra-slow oscillations in the rat olivary pretectal nucleus. AB - A subpopulation of olivary pretectal nucleus (OPN) neurons discharges action potentials in an oscillatory manner, with a period of approximately two minutes. This 'infra-slow' oscillatory activity depends on synaptic excitation originating in the retina. Signals from rod-cone photoreceptors reach the OPN via the axons of either classic retinal ganglion cells or intrinsically photosensitive retinal ganglion cells (ipRGCs), which use melanopsin for photon capturing. Although both cell types convey light information, their physiological functions differ considerably. The aim of the present study was to disentangle how rod-cone and melanopsin photoresponses contribute to generation of oscillatory activity. Pharmacological manipulations of specific phototransduction cascades were used whilst recording extracellular single-unit activity in the OPN of anaesthetized rats. The results show that under photopic conditions (bright light), ipRGCs play a major role in driving infra-slow oscillations, as blocking melanopsin phototransmission abolishes or transiently disturbs oscillatory firing of the OPN neurons. On the other hand, blocking rod-cone phototransmission does not change firing patterns in photopic conditions. However, under mesopic conditions (moderate light), when melanopsin phototransmission is absent, blocking rod-cone signalling causes disturbances or even the disappearance of oscillations implying that classic photoreceptors are of greater importance under moderate light. Evidence is provided that all photoreceptors are required for the generation of oscillations in the OPN, although their roles in driving the rhythm are determined by the lighting conditions, consistent with their relative sensitivities. The results further suggest that maintained retinal activity is crucial to observe infra-slow oscillatory activity in the OPN. PMID- 26804184 TI - Efficient elimination of caffeine from water using Oxone activated by a magnetic and recyclable cobalt/carbon nanocomposite derived from ZIF-67. AB - To eliminate caffeine, one of the most common pharmaceuticals and personal care products, from water, Oxone (peroxymonosulfate salt) was proposed to degrade it. To accelerate the generation of sulfate radicals from Oxone, a magnetic cobalt/carbon nanocomposite (CCN) was prepared from a one-step carbonization of a cobalt-based Zeolitic Imidazolate Framework (ZIF-67). The resultant CCN exhibits immobilized cobalt and increased porosity, and can be magnetically manipulated. These characteristics make CCN a promising heterogeneous catalyst to activate Oxone for caffeine degradation. Factors affecting the caffeine degradation were investigated, including CCN loading, Oxone dosage, temperature, pH, surfactants, salts and inhibitors. A higher CCN loading, Oxone dosage and temperature greatly improved the caffeine degradation by CCN-activated Oxone. Acidic conditions were also preferable over basic conditions for caffeine degradation. The addition of cetyltrimethylammonium bromide (CTAB) and NaCl both significantly hindered caffeine degradation because bromide from CTAB and chloride from NaCl scavenged sulfate radicals. Based on the effects of inhibitors (i.e., methanol and tert butyl alcohol), the caffeine degradation by CCN-activated Oxone was considered to primarily involve sulfate radicals and, less commonly, hydroxyl radicals. The intermediates generated during the caffeine degradation were analyzed using GC-MS and a possible degradation pathway was proposed. CCN was also able to activate Oxone for caffeine degradation for multiple cycles without changing its catalytic activity. These features reveal that CCN is an effective and promising catalyst for the activation of Oxone for the degradation of caffeine. PMID- 26804182 TI - Stretch-Induced Drug Delivery from Superhydrophobic Polymer Composites: Use of Crack Propagation Failure Modes for Controlling Release Rates. AB - The concept of using crack propagation in polymeric materials to control drug release and its first demonstration are reported. The composite drug delivery system consists of highly-textured superhydrophobic electrosprayed microparticle coatings, composed of biodegradable and biocompatible polymers poly(caprolactone) and poly(glycerol monostearate carbonate-co-caprolactone), and a cellulose/polyester core. The release of entrapped agents is controlled by the magnitude of applied strain, resulting in a graded response from water infiltration through the propagating patterned cracks in the coating. Strain dependent delivery of the anticancer agents cisplatin and 7-ethyl-10 hydroxycamptothecin to esophageal cancer cells (OE33) in vitro is observed. Finally the device is integrated with an esophageal stent to demonstrate delivery of fluorescein diacetate, using applied tension, to an ex vivo esophagus. PMID- 26804185 TI - Bullying victimization in adolescence and psychotic symptomatology in adulthood: evidence from a 35-year study. AB - BACKGROUND: There has been considerable recent interest in possible causal linkages between exposure to bullying victimization and later psychotic symptomatology. Prior research in this area has had several limitations which make it difficult to ascertain causality, and to determine the extent to which these effects extend beyond adolescence. METHOD: Data were obtained from the Christchurch Health and Development Study, a 35-year study of a longitudinal birth cohort. This investigation used generalized estimating equation modelling to estimate the associations between bullying victimization (ages 13-16 years) and psychotic symptoms (ages 18-35 years), before and after controlling for possible confounding factors, including: gender; childhood socio-economic status; child intelligence quotient; exposure to sexual abuse in childhood; anxious/withdrawn behaviour and attention problems (ages 7-9 years); and adolescent psychotic symptoms and paranoid ideation (ages 15-16 years). RESULTS: There was a significant (p < 0.0001) bivariate association between bullying victimization in adolescence and psychotic symptomatology in adulthood. Successive models controlling for covariation reduced this association to statistical non-significance. After controlling for covariates, those with the highest level of bullying victimization had rates of psychotic symptoms that were 1.21 (95% confidence interval 0.73-1.99) times higher than those who were not victimized. CONCLUSIONS: The association between bullying victimization in adolescence and psychotic symptomatology in adulthood could be largely explained by childhood behavioural problems, and exposure to sexual abuse in childhood. The results suggest that bullying victimization was unlikely to have been a cause of adult psychotic symptoms, but bullying victimization remained a risk marker for these symptoms. PMID- 26804186 TI - Influence of Electric Fields and Conductivity on Pollen Tube Growth assessed via Electrical Lab-on-Chip. AB - Pollen tubes are polarly growing plant cells that are able to rapidly respond to a combination of chemical, mechanical, and electrical cues. This behavioural feature allows them to invade the flower pistil and deliver the sperm cells in highly targeted manner to receptive ovules in order to accomplish fertilization. How signals are perceived and processed in the pollen tube is still poorly understood. Evidence for electrical guidance in particular is vague and highly contradictory. To generate reproducible experimental conditions for the investigation of the effect of electric fields on pollen tube growth we developed an Electrical Lab-on-Chip (ELoC). Pollen from the species Camellia displayed differential sensitivity to electric fields depending on whether the entire cell or only its growing tip was exposed. The response to DC fields was dramatically higher than that to AC fields of the same strength. However, AC fields were found to restore and even promote pollen growth. Surprisingly, the pollen tube response correlated with the conductivity of the growth medium under different AC frequencies--consistent with the notion that the effect of the field on pollen tube growth may be mediated via its effect on the motion of ions. PMID- 26804187 TI - Endoscopic Endonasal Repair of Cerebrospinal Fluid Leakage Caused by a Rare Traumatic Clival Fracture. AB - An 89-year-old male presented with cerebrospinal fluid (CSF) rhinorrhea associated with head trauma sustained as a pedestrian in a traffic accident. Computed tomography (CT) showed pneumocephalus and multiple cranial bone fractures, including the clivus. Although the CSF rhinorrhea was treated conservatively for a week, clinical symptoms did not improve and surgical repair was performed. Preoperative thin-sliced bone CT and steady-state magnetic resonance images revealed a bone defect at the middle clivus and a collection of CSF fluid from the clival fistula in the sphenoid sinus. Endoscopic endonasal reconstruction was performed, and the 3-mm diameter dural tear and bone defect at the middle clivus were well visualized. The fistula was repaired using a pedicled nasoseptal mucosal flap. The CSF rhinorrhea completely disappeared as a result of the endoscopic endonasal surgery. The present report describes a rare case of CSF rhinorrhea caused by a traumatic clival fracture and surgical management by endoscopic endonasal surgery. PMID- 26804188 TI - Desmoplastic Fibroma of the Pediatric Cranium: An Aggressive Skull Tumor with Local Recurrence. AB - Cranial desmoplastic fibroma (DF) is extremely rare and only 20 cases, including only 7 pediatric cases, have been reported previously. We describe the first case of a child with cranial DF that increased in size over a short-term and recurred after resection. The aim of this case report was to discuss the clinical, radiological, and histological characteristics and optimal treatment for this rare and aggressive skull tumor. PMID- 26804189 TI - Fungal Internal Carotid Artery Aneurysm Treated by Trapping and High-Flow Bypass: A Case Report and Literature Review. AB - We report a case of unruptured fungal internal carotid artery (ICA) aneurysm and review the pertinent literature. A 79-year-old man presented with decreased visual acuity on the right side, and he was diagnosed with retrobulbar optic neuritis. Medical treatment with steroids resulted in Aspergillus meningoencephalitis spreading to the bottom of bilateral frontal lobes, caused by an intracranial extension of sphenoid sinusitis. Magnetic resonance imaging (MRI) performed 26 days after the start of antifungal therapy showed a denovo right ICA aneurysm projecting anteriorly into the sphenoid sinus. As the aneurysm grew rapidly, it was trapped surgically after establishing a high-flow bypass from the external carotid artery to the middle cerebral artery. The patient's postoperative course was uneventful. Anti-fungal medication was continued until plasma concentrations of beta-D-glucan decreased to within normal limits. Although fungal ICA aneurysm carries a high mortality rate, early detection and prompt treatment by trapping and high-flow bypass can lead to good clinical outcome. PMID- 26804190 TI - Reappearance of Cranial Nerve Dysfunction Symptoms Caused by New Artery Compression More than 20 Years after Initially Successful Microvascular Decompression: Report of Two Cases. AB - Reappearance of symptoms of cranial nerve dysfunction is not uncommon after successful microvascular decompression (MVD). The purpose of this study was to report two quite unusual cases of recurrent and newly developed hemifacial spasm (HFS) caused by a new conflicting artery more than 20 years after the first successful surgery. In Case 1, the first MVD was performed for HFS caused by the posterior inferior cerebellar artery (PICA) when the patient was 38 years old. After 26 symptom-free years, HFS recurred on the same side of the face due to compression by the newly developed offending AICA. In Case 2, the patient was first operated on for trigeminal neuralgia by transposition of the AICA at 49 years old, but 20 symptom-free years after the first MVD, a new offending PICA compressed the facial nerve on the same side, causing HFS. These two patients underwent reoperation and gained satisfactory results postoperatively. Reappearance of symptoms related to compression of the root exit zone (REZ) by a new offending artery after such a long symptom-free interval since the first effective MVD is rare. Here, we describe two such unusual cases and discuss how to manage and prevent such reappearance of symptoms after a long time interval. PMID- 26804191 TI - Hierarchical self-assembly of switchable nucleolipid supramolecular gels based on environmentally-sensitive fluorescent nucleoside analogs. AB - Exquisite recognition and folding properties have rendered nucleic acids as useful supramolecular synthons for the construction of programmable architectures. Despite their proven applications in nanotechnology, scalability and fabrication of nucleic acid nanostructures still remain a challenge. Here, we describe a novel design strategy to construct new supramolecular nucleolipid synthons by using environmentally-sensitive fluorescent nucleoside analogs, based on 5-(benzofuran-2-yl)uracil and 5-(benzo[b]thiophen-2-yl)uracil cores, as the head group and fatty acids, attached to the ribose sugar, as the lipophilic group. These modified nucleoside-lipid hybrids formed organogels driven by hierarchical structures such as fibers, twisted ribbons, helical ribbons and nanotubes, which depended on the nature of fatty acid chain and nucleobase modification. NMR, single crystal X-ray and powder X-ray diffraction studies revealed the coordinated interplay of various non-covalent interactions invoked by modified nucleobase, sugar and fatty acid chains in setting up the pathway for the gelation process. Importantly, these nucleolipid gels retained or displayed aggregation-induced enhanced emission and their gelation behavior and photophysical properties could be reversibly switched by external stimuli such as temperature, ultrasound and chemicals. Furthermore, the switchable nature of nucleolipid gels to chemical stimuli enabled the selective two channel recognition of fluoride and Hg(2+) ions through visual phase transition and fluorescence change. Fluorescent organogels exhibiting such a combination of useful features is rare, and hence, we expect that this innovative design of fluorescent nucleolipid supramolecular synthons could lead to the emergence of a new family of smart optical materials and probes. PMID- 26804193 TI - Intra-cerebral and intra-nasal melanocortin-4 receptor antagonist blocks withdrawal hyperalgesia in alcohol-dependent rats. AB - Humans diagnosed with alcohol use disorder are more sensitive to painful stimuli during withdrawal, which suggests that excessive alcohol drinking worsens pain outcomes. Alcohol-dependent rats exhibit increases in nociceptive sensitivity during withdrawal. Data from animal models suggest that brain melanocortin-4 receptors (MC4Rs) mediate alcohol drinking and nociception. Here we tested: (1) the effect of alcohol dependence on thermal nociception in rats, and (2) the ability of acute alcohol and (3) MC4R antagonists to reverse hyperalgesia during withdrawal in alcohol-dependent rats. Rats were trained to self-administer operant alcohol and were tested for baseline thermal nociception. Half of the rats were made dependent on alcohol, then all rats were cannulated in the lateral ventricle. We tested the effects of acute alcohol drinking, acute fixed-dose alcohol, intra-ventricular agouti-related protein (endogenous MC4R antagonist), intra-ventricular HS014 (synthetic MC4R antagonist) and intra-nasal HS014 on hyperalgesia during withdrawal in alcohol-dependent rats, relative to non dependent drinkers and alcohol-naive controls. Alcohol-dependent rats exhibit thermal hyperalgesia that is abolished by alcohol drinking, bolus alcohol and intra-ventricular and intra-nasal MC4R antagonists. These manipulations did not affect thermal nociception in non-dependent drinkers and alcohol-naive controls, suggesting that alcohol dependence produces neuroadaptations in brain MC4R systems. These results suggest that brain MC4R systems may be an effective therapeutic target for reducing nociception in the alcohol-dependent organism. PMID- 26804195 TI - Systematic community- and hospital-based surveillance for enterovirus-D68 in three Canadian provinces, August to December 2014. AB - Respiratory specimens collected from outpatients with influenza-like illness in three Canadian provinces (British Columbia (BC), Alberta and Quebec) participating in a community-based sentinel surveillance network were prospectively screened for enterovirus-D68 (EV-D68) from 1 August to 31 December 2014 and compared to specimens collected from 1 October 2013 to 31 July 2014. Eighteen (1%) of 1,894 specimens were EV-D68-positive: 1/348 (0.3%) collected from October to December 2013 and 11/460 (2.4%) from October to December 2014, an eight-fold increase in detection rates (p=0.01), consistent with epidemic circulation in autumn 2014. The remaining EV-D68 detections were in September 2014 (6/37). Enhanced passive surveillance was also conducted on all inpatient and outpatient EV-D68 cases (n=211) detected at the BC provincial reference laboratory from 28 August to 31 December 2014. Incidence of hospitalisations was 3/100,000 overall and 21, 17, 4 and 1/100,000 among those<5, 5-9, 10-19 and >=20 years-old with male-to-female ratios>1 among paediatric but not adult cases. Three cases in BC with comorbidity or co-infection died and five exhibited neurological features persisting >9 months. Active surveillance in outpatient and inpatient settings is needed from more areas and additional seasons to better understand EV-D68 epidemiology and potential at-risk groups for severe or unusual manifestations. PMID- 26804198 TI - Climate Change Conceptual Change: Scientific Information Can Transform Attitudes. AB - Of this article's seven experiments, the first five demonstrate that virtually no Americans know the basic global warming mechanism. Fortunately, Experiments 2-5 found that 2-45 min of physical-chemical climate instruction durably increased such understandings. This mechanistic learning, or merely receiving seven highly germane statistical facts (Experiment 6), also increased climate-change acceptance-across the liberal-conservative spectrum. However, Experiment 7's misleading statistics decreased such acceptance (and dramatically, knowledge confidence). These readily available attitudinal and conceptual changes through scientific information disconfirm what we term "stasis theory"--which some researchers and many laypeople varyingly maintain. Stasis theory subsumes the claim that informing people (particularly Americans) about climate science may be largely futile or even counterproductive--a view that appears historically naive, suffers from range restrictions (e.g., near-zero mechanistic knowledge), and/or misinterprets some polarization and (noncausal) correlational data. Our studies evidenced no polarizations. Finally, we introduce HowGlobalWarmingWorks.org--a website designed to directly enhance public "climate-change cognition." PMID- 26804196 TI - Inhibition of Lysyl Oxidase and Lysyl Oxidase-Like Enzymes Has Tumour-Promoting and Tumour-Suppressing Roles in Experimental Prostate Cancer. AB - Lysyl oxidase (LOX) and LOX-like (LOXL) enzymes are key players in extracellular matrix deposition and maturation. LOX promote tumour progression and metastasis, but it may also have tumour-inhibitory effects. Here we show that orthotopic implantation of rat prostate AT-1 tumour cells increased LOX and LOXLs mRNA expressions in the tumour and in the surrounding non-malignant prostate tissue. Inhibition of LOX enzymes, using Beta-aminopropionitrile (BAPN), initiated before implantation of AT-1 cells, reduced tumour growth. Conversely, treatment that was started after the tumours were established resulted in unaffected or increased tumour growth. Moreover, treatment with BAPN did not suppress the formation of spontaneous lymph node metastases, or lung tumour burden, when tumour cells were injected intravenously. A temporal decrease in collagen fibre content, which is a target for LOX, was observed in tumours and in the tumour-adjacent prostate tissue. This may explain why early BAPN treatment is more effective in inhibiting tumour growth compared to treatment initiated later. Our data suggest that the enzymatic function of the LOX family is context-dependent, with both tumour suppressing and tumour-promoting properties in prostate cancer. Further investigations are needed to understand the circumstances under which LOX inhibition may be used as a therapeutic target for cancer patients. PMID- 26804199 TI - Improved Quantification of Free and Ester-Bound Gallic Acid in Foods and Beverages by UHPLC-MS/MS. AB - Hydrolyzable tannins are measured routinely during the characterization of food and beverage samples. Most methods for the determination of hydrolyzable tannins use hydrolysis or methanolysis to convert complex tannins to small molecules (gallic acid, methyl gallate, and ellagic acid) for quantification by HPLC-UV. Often unrecognized, analytical limitations and variability inherent in these approaches for the measurement of hydrolyzable tannins include the variable mass fraction (0-0.90) that is released as analyte, contributions of sources other than tannins to hydrolyzable gallate (can exceed >10 wt %/wt), the measurement of both free and total analyte, and lack of controls to account for degradation. An accurate, specific, sensitive, and higher-throughput approach for the determination of hydrolyzable gallate based on ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) that overcomes these limitations was developed. PMID- 26804200 TI - A distinct X-linked syndrome involving joint contractures, keloids, large optic cup-to-disc ratio, and renal stones results from a filamin A (FLNA) mutation. AB - We further evaluated a previously reported family with an apparently undescribed X-linked syndrome involving joint contractures, keloids, an increased optic cup to-disc ratio, and renal stones to elucidate the genetic cause. To do this, we obtained medical histories and performed physical examination on 14 individuals in the family, five of whom are affected males and three are obligate carrier females. Linkage analysis was performed on all but one individual and chromosome X-exome sequencing was done on two affected males. The analysis localized the putative gene to Xq27-qter and chromosome X-exome sequencing revealed a mutation in exon 28 (c.4726G>A) of the filamin A (FLNA) gene, predicting that a conserved glycine had been replaced by arginine at amino acid 1576 (p.G1576R). Segregation analysis demonstrated that all known carrier females tested were heterozygous (G/A), all affected males were hemizygous for the mutation (A allele) and all normal males were hemizygous for the normal G allele. The data and the bioinformatic analysis indicate that the G1576R mutation in the FLNA gene is very likely pathogenic in this family. The syndrome affecting the family shares phenotypic overlap with other syndromes caused by FLNA mutations, but appears to be a distinct phenotype, likely representing a unique genetic syndrome. PMID- 26804203 TI - Biodiversity of autolytic ability in flocculent Saccharomyces cerevisiae strains suitable for traditional sparkling wine fermentation. AB - Yeasts involved in secondary fermentation of traditional sparkling wines should show specific characteristics, such as flocculation capacity and autolysis. Recently it has been postulated that autophagy may contribute to the outcome of autolysis. In this study, 28 flocculent wine Saccahromyces cerevisiae strains characterized by different flocculation degrees were studied for their autolytic and autophagic activities. Autolysis was monitored in synthetic medium through the determination of amino acid nitrogen and total proteins released. At the same time, novel primer sets were developed to determine the expression of the genes ATG1, ATG17 and ATG29. Twelve strains were selected on the basis of their autolytic rate and ATG gene expressions in synthetic medium and were inoculated in a base wine. After 30, 60 and 180 days the autolytic process and ATG gene expressions were evaluated. The obtained data showed that autolysis and ATG gene expressions differed among strains and were independent of the degree of flocculation. This biodiversity could be exploited to select new starter stains to improve sparkling wine production. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26804201 TI - Global selection of Plasmodium falciparum virulence antigen expression by host antibodies. AB - Parasite proteins called PfEMP1 that are inserted on the surface of infected erythrocytes, play a key role in the severe pathology associated with infection by the Plasmodium falciparum malaria parasite. These proteins mediate binding of infected cells to the endothelial lining of blood vessels as a strategy to avoid clearance by the spleen and are major targets of naturally acquired immunity. PfEMP1 is encoded by a large multi-gene family called var. Mutually-exclusive transcriptional switching between var genes allows parasites to escape host antibodies. This study examined in detail the patterns of expression of var in a well-characterized sample of parasites from Kenyan Children. Instead of observing clear inverse relationships between the expression of broad sub-classes of PfEMP1, we found that expression of different PfEMP1 groups vary relatively independently. Parasite adaptation to host antibodies also appears to involve a general reduction in detectable var gene expression. We suggest that parasites switch both between different PfEMP1 variants and between high and low expression states. Such a strategy could provide a means of avoiding immunological detection and promoting survival under high levels of host immunity. PMID- 26804204 TI - Spontaneously Arising Canine Glioma as a Potential Model for Human Glioma. AB - Human gliomas are malignant brain tumours that carry a poor prognosis and are composed of a heterogeneous population of cells. There is a paucity of animal models available for study of these tumours and most have been created by genetic modification. Spontaneously arising canine gliomas may provide a model for the characterization of the human tumours. The present study shows that canine gliomas form a range of immunohistochemical patterns that are similar to those described for human gliomas. The in-vitro sphere assay was used to analyze the expansion and differentiation potential of glioma cells taken from the periphery and centre of canine tumours. Samples from the subventricular zone (SVZ) and contralateral parenchyma were used as positive and negative controls, respectively. The expansion potential for all of these samples was low and cells from only three cultures were expanded for six passages. These three cultures were derived from high-grade gliomas and the cells had been cryopreserved. Most of the cells obtained from the centre of the tumours formed spheres and were expanded, in contrast to samples taken from the periphery of the tumours. Spheres were also formed and expanded from two areas of apparently unaffected brain parenchyma. The neurogenic SVZ contralateral samples also contained progenitor proliferating cells, since all of them were expanded for three to five passages. Differentiation analysis showed that all cultured spheres were multipotential and able to differentiate towards both neurons and glial cells. Spontaneously arising canine gliomas might therefore constitute an animal model for further characterization of these tumours. PMID- 26804205 TI - The effects of LPS on the activity of Trp-containing antimicrobial peptides against Gram-negative bacteria and endotoxin neutralization. AB - A series of synthesized Trp-containing antimicrobial peptides showed significantly different antimicrobial activity against Gram-negative bacteria despite having similar components and amino acid sequences and the same net positive charge and hydrophobicity. Lipopolysaccharide (LPS) in the outer membrane is a permeability barrier to prevent antimicrobial peptides from crossing into Gram-negative bacteria. We investigated the interaction of five Trp containing peptides, I1W, I4W, L5W, L11W and L12W, with LPS using circular dichroism (CD), IR spectroscopy, isothermal titration calorimetry (ITC), dynamic light scattering (DLS), zeta-potential measurements and confocal laser scanning microscopy, to address whether bacterial LPS is responsible for the different susceptibilities of Gram-negative bacteria to Trp-containing peptides. Our data indicate that I1W and I4W penetrated the LPS layer and killed Gram-negative bacteria by a "self-promoted uptake" pathway in which the peptides first approach LPS by electrostatic forces and then dissociate LPS micelle. This process results in disorganization of the LPS leaflet and promotes the ability of the peptide to cross the outer membrane into the inner membrane and disrupt the cytoplasmic membrane. Although L5W, L11W and L12W strongly bind to LPS bilayers and depolarize bacterial cytoplasmic membranes, similar to I1W and I4W, they are unable to destabilize LPS aggregates and traverse through the tightly packed LPS molecules. This study increases our understanding of the mechanism of action of these peptides in the LPS outer membrane and will help in the development of a potent broad-spectrum antibiotic for future therapeutic purposes. STATEMENT OF SIGNIFICANCE: Tryptophan (Trp) residues show a strong preference for the interfacial region of biological membranes, and this property endows Trp containing peptides with the unique ability to interact with the surface of bacterial cell membranes. In this manuscript, we report the membrane interaction of Trp-containing peptide to address whether bacterial LPS is responsible for the different susceptibilities of Gram-negative bacteria to Trp-containing peptides. Based on the data collected, we propose a molecular mechanism for the peptide-LPS interactions that allows the peptides to traverse or prevents them from transversing the LPS layer and the target inner membrane. The data should help in the development of a potent broad-spectrum antibiotic for future therapeutic purposes. PMID- 26804206 TI - Bacteria-responsive multilayer coatings comprising polycationic nanospheres for bacteria biofilm prevention on urinary catheters. AB - This work reports on the development of infection-preventive coatings on silicone urinary catheters that contain in their structure and release on demand antibacterial polycationic nanospheres. Polycationic aminocellulose conjugate was first sonochemically processed into nanospheres to improve its antibacterial potential compared to the bulk conjugate in solution (ACSol). Afterward the processed aminocellulose nanospheres (ACNSs) were combined with the hyaluronic acid (HA) polyanion to build a layer-by-layer construct on silicone surfaces. Although the coating deposition was more effective when HA was coupled with ACSol than with ACNSs, the ACNSs-based coatings were thicker and displayed smoother surfaces due to the embedment of intact nanospheres. The antibacterial effect of ACNSs multilayers was 40% higher compared to ACSol coatings. This fact was further translated into more effective prevention of Pseudomonas aeruginosa biofilm formation. The coatings were stable in the absence of bacteria, whereas their disassembling occurred gradually during incubation with P. aeruginosa, and thus eradicate the biofilm upon release of antibacterial agents. Only 5 bilayers of HA/ACNSs were sufficient to prevent the biofilm formation, in contrast to the 10 bilayers of ACSol required to achieve the same effect. The antibiofilm efficiency of (HA/ACNSs)10 multilayer construct built on a Foley catheter was additionally validated under dynamic conditions using a model of the catheterized bladder in which the biofilm was grown during seven days. STATEMENT OF SIGNIFICANCE: Antibacterial layer-by-layer coatings were fabricated on silicone that efficiently prevents Pseudomonas aeruginosa biofilm formation during time beyond the useful lifetime of the currently employed urinary catheters in medical practice. The coatings are composed of intact, highly antibacterial polycationic nanospheres processed from aminated cellulose and bacteria-degrading glycosaminoglycan hyaluronic acid. The importance of incorporating nanoscale structures within bacteria-responsive surface coatings to impart durable antibacterial and self-defensive properties to the medical indwelling devices is highlighted. PMID- 26804207 TI - Comparison of clinical and radiographic status around dental implants placed in patients with and without prediabetes: 1-year follow-up outcomes. AB - OBJECTIVE: We hypothesized that peri-implant soft tissue inflammation is worse and peri-implant marginal bone loss (MBL) is higher around dental implants placed in patients with prediabetes compared to healthy subjects. The aim of the present 12-month follow-up study was to compare the clinical and radiographic status around dental implants placed in patients with and without prediabetes. MATERIAL AND METHODS: Twelve patients with medically diagnosed prediabetes (Group-1) and 12 controls (Group-2) were included. All patients were indicated for single tooth maxillary or mandibular premolar replacement with the adjacent teeth intact. Success of the restored implants was assessed by comparing clinical (peri-implant bleeding on probing [BOP], and probing pocket depth [PPD]) and radiographic (peri implant MBL) parameters at baseline and at 12-months follow-up. Statistical analysis was performed using one-way analysis of variance, and P-values <0.05 were considered statistically significant. RESULTS: At 12 months of follow-up, there was no clinical evidence for the presence of plaque, BOP and peri-implant pockets with PPD >= 4 mm in both groups. At 12-month follow-up, the mean MBL among implants placed in groups 1 and 2 were 0.2 +/- 0.1 mm and 0.1 +/- 0.01 mm, respectively. Overall, the periodontal status (PI, BOP and PPD >= 4 mm) at 12 month follow-up was comparable among patients in both groups. CONCLUSION: Within the limitations of this study, it is concluded that dental implants inserted in prediabetic and healthy patients have similar success rates and remain clinically and radiographically stable after 1-year follow-up. PMID- 26804208 TI - Loss of CAR promotes migration and proliferation of HaCaT cells, and accelerates wound healing in rats via Src-p38 MAPK pathway. AB - The coxsackie and adenovirus receptor (CAR) is a cell adhesion molecule mostly localized to cell-cell contacts in epithelial and endothelial cells. CAR is known to regulate tumor progression, however, its physiological role in keratinocyte migration and proliferation, two essential steps in re-epithelialization during wound healing, has less been investigated. Here we showed that CAR was predominantly expressed in the epidermis of human skin, CAR knockdown by RNAi significantly accelerated HaCaT cell migration and proliferation. In addition, knockdown of CAR in vitro increased p-Src, p-p38, and p-JNK protein levels; however, Src inhibitor PP2 prevented the increase of p-Src and p-p38 induced by CAR RNAi, but not p-JNK, and decelerated cell migration and proliferation. More intriguingly, in vivo CAR RNAi on the skin area surrounding the wounds on rat back visually accelerated wound healing and re-epithelialization process, while treatment with PP2 or p38 inhibitor SB203580 obviously inhibited these effects. By contrast, overexpressing CAR in HaCaT cells significantly decelerated cell migration and proliferation. Above results demonstrate that suppression of CAR could accelerate HaCaT cell migration and proliferation, and promote wound healing in rat skin, probably via Src-p38 MAPK pathway. CAR thus might serve as a novel therapeutic target for facilitating wound healing. PMID- 26804209 TI - miRNA Regulation of Immune Tolerance in Early Pregnancy. AB - To support embryo implantation, the female reproductive tract must provide a tolerogenic immune environment. Seminal fluid contact at conception contributes to activating the endometrial gene expression and immune cell changes required for robust implantation, influencing not only the quality of the ensuing pregnancy but also the health of offspring. miRNAs are small non-coding RNAs that play important regulatory roles in biological processes, including regulation of the immune environment. miRNAs are known to contribute to gene regulation in pregnancy and are altered in pregnancy pathologies. Recent studies indicate that miRNAs participate in establishing immune tolerance at conception, and may contribute to the regulatory effects of seminal fluid in generating tolerogenic dendritic cells and T regulatory cells. This review highlights those miRNAs implicated in programming immune cells that are critical during the peri conception period and explores how seminal fluid may regulate female tract miRNA expression following coitus. PMID- 26804210 TI - Recent Literature on Medication Errors and Adverse Drug Events in Older Adults. AB - Medication errors and adverse drug events are common in older adults, but locating literature addressing these issues is often challenging. The objective of this article is to summarize recent studies addressing medication errors and adverse drug events in a single location to improve accessibility for individuals working with older adults. A comprehensive literature search for studies published in 2014 was conducted, and 51 potential articles were identified. After critical review, 17 studies were selected for inclusion based on innovation; rigorous observational or experimental study designs; and use of reliable, valid measures. Four articles characterizing potentially inappropriate prescribing and interventions to optimize medication regimens were annotated and critiqued in detail. The authors hope that health policy-makers and clinicians find this information helpful in improving the quality of care for older adults. PMID- 26804211 TI - Atypical IkappaB proteins in immune cell differentiation and function. AB - The NF-kappaB/Rel signalling pathway plays a crucial role in numerous biological processes, including innate and adaptive immunity. NF-kappaB is a family of transcription factors, whose activity is regulated by the inhibitors of NF-kappaB (IkappaB). The IkappaB proteins comprise two distinct groups, the classical (cytoplasmic) and the atypical (nuclear) IkappaB proteins. Although the cytoplasmic regulation of NF-kappaB is well characterised, its nuclear regulation mechanisms remain marginally elucidated. However, work from recent years indicated that nuclear IkappaBs contribute significantly to the modulation of NF kappaB-mediated transcription in the immune system. Here, we discuss the role of the atypical IkappaB proteins Bcl-3, IkappaBzeta, IkappaBNS, IkappaBeta and IkappaBL for the regulation of gene expression and effector functions in immune cells. PMID- 26804212 TI - Microcystbiopterins A-E, five O-methylated biopterin glycosides from two Microcystis spp. bloom biomasses. AB - Five previously undescribed biopterin glycosides, microcystbiopterin A-E, were isolated from the extracts of two bloom materials of Microcystis spp. collected from a fishpond (IL-337) and Lake Kinneret (IL-347), Israel. The structure of the pterins was established by interpretation of their UV, CD, 1D and 2D NMR spectra and HR mass measurements. Microcystbiopterin D is the first heptose containing pterin glycoside to be reported in the literature. Their antimicrobial and cytotoxic properties were evaluated but all were found not active in both assays. PMID- 26804213 TI - Degradation of Methylammonium Lead Iodide Perovskite Structures through Light and Electron Beam Driven Ion Migration. AB - Organometal halide perovskites show promising features for cost-effective application in photovoltaics. The material instability remains a major obstacle to broad application because of the poorly understood degradation pathways. Here, we apply simultaneous luminescence and electron microscopy on perovskites for the first time, allowing us to monitor in situ morphology evolution and optical properties upon perovskite degradation. Interestingly, morphology, photoluminescence (PL), and cathodoluminescence of perovskite samples evolve differently upon degradation driven by electron beam (e-beam) or by light. A transversal electric current generated by a scanning electron beam leads to dramatic changes in PL and tunes the energy band gaps continuously alongside film thinning. In contrast, light-induced degradation results in material decomposition to scattered particles and shows little PL spectral shifts. The differences in degradation can be ascribed to different electric currents that drive ion migration. Moreover, solution-processed perovskite cuboids show heterogeneity in stability which is likely related to crystallinity and morphology. Our results reveal the essential role of ion migration in perovskite degradation and provide potential avenues to rationally enhance the stability of perovskite materials by reducing ion migration while improving morphology and crystallinity. It is worth noting that even moderate e-beam currents (86 pA) and acceleration voltages (10 kV) readily induce significant perovskite degradation and alter their optical properties. Therefore, attention has to be paid while characterizing such materials using scanning electron microscopy or transmission electron microscopy techniques. PMID- 26804215 TI - Discussion. PMID- 26804214 TI - Treatment and outcomes of aortic endograft infection. AB - OBJECTIVE: This study examined the medical and surgical management and outcomes of patients with aortic endograft infection after abdominal endovascular aortic repair (EVAR) or thoracic endovascular aortic repair (TEVAR). METHODS: Patients diagnosed with infected aortic endografts after EVAR/TEVAR between January 1, 2004, and January 1, 2014, were reviewed using a standardized, multi institutional database. Demographic, comorbidity, medical management, surgical, and outcomes data were included. RESULTS: An aortic endograft infection was diagnosed in 206 patients (EVAR, n = 180; TEVAR, n = 26) at a mean 22 months after implant. Clinical findings at presentation included pain (66%), fever/chills (66%), and aortic fistula (27%). Ultimately, 197 patients underwent surgical management after a mean of 153 days. In situ aortic replacement was performed in 186 patients (90%) using cryopreserved allograft in 54, neoaortoiliac system in 21, prosthetic in 111 (83% soaked in antibiotic), and 11 patients underwent axillary-(bi)femoral bypass. Graft cultures were primarily polymicrobial (35%) and gram-positive (22%). Mean hospital length of stay was 23 days, with perioperative 30-day morbidity of 35% and mortality of 11%. Of the nine patients managed only medically, four of five TEVAR patients died after mean of 56 days and two of four EVAR patients died; both deaths were graft-related (mean follow-up, 4 months). Nineteen replacement grafts were explanted after a mean of 540 days and were most commonly associated with prosthetic graft material not soaked in antibiotic and extra-anatomic bypass. Mean follow-up was 21 months, with life-table survival of 70%, 65%, 61%, 56%, and 51% at 1, 2, 3, 4, and 5 years, respectively. CONCLUSIONS: Aortic endograft infection can be eradicated by excision and in situ or extra-anatomic replacement but is often associated with early postoperative morbidity and mortality and occasionally with a need for late removal for reinfection. Prosthetic graft replacement after explanation is associated with higher reinfection and graft-related complications and decreased survival compared with autogenous reconstruction. PMID- 26804216 TI - An externally validated robust risk predictive model of adverse outcomes after carotid endarterectomy. AB - BACKGROUND: The goal of this study was to construct and externally validate a risk prediction model for patients who undergo carotid endarterectomy (CEA). METHODS: The Vascular Study Group of New England (VSGNE) and Vascular Quality Initiative (VQI) databases were queried for patients who underwent CEA. Data on perioperative variables, comorbidities, and medications were entered into a logistic regression model as predictors of the composite adverse outcomes in the VSGNE sample. Adverse outcomes were defined if the patient experienced any of the following events: postoperative stroke, myocardial infarction, mortality, or discharge to rehabilitation facility. Backward elimination (alpha level of .2) was then used to select a more parsimonious model. Calibration was performed to measure how closely predicted outcomes agreed with observed outcomes. To assess calibration we used Hosmer-Lemeshow test, the predictive value of the model was assessed via the C-statistic. The external validation was then performed using the VQI sample after excluding those in the VSGNE sample (VQI-VSGNE) following a similar method. RESULTS: The constructed model showed a substantial predictive capability of adverse outcomes (C = 0.711) with goodness of fit (Hosmer-Lemeshow lack of fit test, P = .494). A significantly higher rate of adverse outcomes was noted for the VQI sample (5.2%; n = 12,075) compared with the VSGNE sample (4.49%; n = 8661; P = .017). The discriminating ability of the VSGNE model remained substantial in the external data (C = 0.702). CONCLUSIONS: The internally validated VSGNE CEA risk model, which robustly predicted adverse outcome after CEA, was externally validated by testing it against the remainder of VQI patients who underwent CEA by a diverse array of physicians. This tool provides a simple and reliable method to risk-stratify CEA patients using only their preoperative conditions. A risk score based on this model can reliably stratify patients according to their risk of adverse outcomes after CEA. PMID- 26804217 TI - Preoperative radial artery volume flow is predictive of arteriovenous fistula outcomes. AB - OBJECTIVE: Guidelines recommend the creation of a wrist radiocephalic arteriovenous fistula (RAVF) as initial hemodialysis vascular access. This study explored the potential of preoperative ultrasound vessel measurements to predict AVF failure to mature (FTM) in a cohort of patients with end-stage renal disease in Northern Ireland. METHODS: A retrospective analysis was performed of all patients who had preoperative ultrasound mapping of upper limb blood vessels carried out from August 2011 to December 2014 and whose AVF reached a functional outcome by March 2015. RESULTS: There were 152 patients (97% white) who had ultrasound mapping and an AVF functional outcome recorded; 80 (54%) had an upper arm AVF created, and 69 (46%) had a RAVF formed. Logistic regression revealed that female gender (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.12 5.55; P = .025), minimum venous diameter (OR, 0.6; 95% CI, 0.39-0.95; P = .029), and RAVF (OR, 0.4; 95% CI, 0.18-0.89; P = .026) were associated with FTM. On subgroup analysis of the RAVF group, RAVFs with an arterial volume flow <50 mL/min were seven times as likely to fail as RAVFs with higher volume flows (OR, 7.0; 95% CI, 2.35-20.87; P < .001). CONCLUSIONS: In this cohort, a radial artery flow rate <50 mL/min was associated with a sevenfold increased risk of FTM in RAVF, which to our knowledge has not been previously reported in the literature. Preoperative ultrasound mapping adds objective assessment in the clinical prediction of AVF FTM. PMID- 26804218 TI - Pediatric nonaortic arterial aneurysms. AB - OBJECTIVE: Pediatric arterial aneurysms are extremely uncommon. Indications for intervention remain poorly defined and treatments vary. The impetus for this study was to better define the contemporary surgical management of pediatric nonaortic arterial aneurysms. METHODS: A retrospective analysis was conducted of 41 children with 61 aneurysms who underwent surgical treatment from 1983 to 2015 at the University of Michigan. Arteries affected included: renal (n = 26), femoral (n = 7), iliac (n = 7), superior mesenteric (n = 4), brachial (n = 3), carotid (n = 3), popliteal (n = 3), axillary (n = 2), celiac (n = 2), ulnar (n = 2), common hepatic (n = 1), and temporal (n = 1). Intracranial aneurysms and aortic aneurysms treated during the same time period were not included in this study. Primary outcomes analyzed were postoperative complications, mortality, and freedom from reintervention. RESULTS: The study included 27 boys and 14 girls, with a median age of 9.8 years (range, 2 months-18 years) and a weight of 31.0 kg (range, 3.8-71 kg). Multiple aneurysms existed in 14 children. Obvious factors that contributed to aneurysmal formation included: proximal juxta-aneurysmal stenoses (n = 14), trauma (n = 12), Kawasaki disease (n = 4), Ehlers-Danlos type IV syndrome (n = 1), and infection (n = 1). Preoperative diagnoses were established using arteriography (n = 23), magnetic resonance angiography (n = 6), computed tomographic arteriography (n = 5), or ultrasonography (n = 7), and confirmed during surgery. Indications for surgery included risk of expansion and rupture, potential thrombosis or embolization of aneurysmal thrombus, local soft tissue and nerve compression, and secondary hypertension in the case of renal artery aneurysms. Primary surgical techniques included: aneurysm resection with reanastomsis, reimplantation, or angioplastic closure (n = 16), interposition (n = 10) or bypass grafts (n = 2), ligation (n = 9), plication (n = 8), endovascular occlusion (n = 3), and nephrectomy (n = 4) in cases of unreconstructable renal aneurysmal disease. Later secondary operations were required to treat stenoses at the site of the original aneurysm repairs (n = 2) and new aneurysmal development (n = 1). Postoperative follow-up averaged 47 months (range, 1-349 months). No major perioperative morbidity and no mortality was encountered in this experience. CONCLUSIONS: Pediatric arterial aneurysms represent a complex disease that affects multiple vascular territories. Results of the current series suggest that individualized surgical treatment, ranging from simple ligations to major arterial reconstructions, was durable and can be undertaken with minimal risk. PMID- 26804219 TI - Total debranching thoracic endovascular aortic arch repair with inflow from the descending thoracic aorta. PMID- 26804220 TI - Cavernous transformation of the portal vein. PMID- 26804222 TI - Fiduciary disparity clarity: Ethics of divided allegiances. AB - An experienced senior vascular surgeon, Dr H. O. Nest, at a university medical center is asked to evaluate a patient with a rare complex vascular problem. The patient is a high-ranking university official, Mr N. Otable, well known to all in the university setting. Dr Nest has had very limited experience with the condition. He has viewed presentations about it but is aware of a world expert at another institution. He discusses transfer with the patient, who agrees on that approach. Later that day, when Dr Nest receives a visit from the Chief-of-Staff and the hospital CEO asking about Mr Otable, they are very concerned that transfer will reflect badly on the medical center's reputation. Dr Nest is strongly requested to reconsider his recommendation--almost at gunpoint. What should he do? A. If he believes that the outcome will be satisfactory, he should schedule the operation. B. He should explain the situation to the patient and let him choose where he wishes to have his surgery. C. He should continue with the plan to refer the patient to another center. D. He must understand his limits and base his decision accordingly. E. He should arrange a conference with the surgeons in the vascular division and the administrators. PMID- 26804221 TI - Outcome of open total arch replacement in the modern era. AB - OBJECTIVE: To shed light on contemporary results of open total aortic arch surgery, we undertook a systematic review to identify all reports on this procedure published in the last 10 years. METHODS: Extensive electronic literature search was undertaken to identify all published articles from 2004 to 2014 that provided results on total aortic arch replacement. According to inclusion and exclusion criteria, 21 relevant studies were selected and meta analyzed to assess outcomes. RESULTS: The pooled estimate for operative mortality was 5.3%. Permanent and transient neurologic deficit occurred postoperatively at a pooled rate of 3.4% and 5.2%, respectively. Pooled rate of irreversible spinal cord injury was 0.6%, whereas renal failure occurred at a pooled rate of 4.1%. Prolonged intubation occurred at pooled rate of 15.4%. Among elective patients, pooled rate of mortality and permanent neurologic deficit was 2.9% and 2.2%, respectively, with a significant difference compared with urgent/emergency surgery cases. CONCLUSIONS: The main findings from this meta-analysis indicate that total aortic arch replacement can be performed with satisfactory mortality and morbidity. The pooled rates of mortality and permanent neurologic deficit among elective cases were surprisingly low, and these data have an even greater prominence when they are compared with outcomes of hybrid arch series. Under urgent/emergency surgery, early mortality and neurologic complications showed an about threefold higher rate. Moderate hypothermic circulatory arrest and early rewarming seem to provide proper renal protection, with an intermediate risk of prolonged intubation. PMID- 26804223 TI - An endovascular filter to prevent embolization during aortic stenting. AB - Endovascular procedures carry an intrinsic risk of distal embolization. A large embolus may occlude major vessels with serious consequences. Endovascular procedures in the thoracic aorta may expose the entire visceral and lower limb circulation to this risk. We describe a method of using an endovascular filter to trap large emboli during thoracic aortic stenting using the Wallstent and describe its use in a case of primary aortic mural thrombus. PMID- 26804224 TI - Rat strain determines statin effect on intimal hyperplasia after carotid balloon injury. PMID- 26804225 TI - Regarding "Recurrent spinal cord ischemia after endovascular stent grafting for chronic traumatic aneurysm of the aortic isthmus". PMID- 26804226 TI - Regarding "Late aortic remodeling persists in the stented segment after endovascular repair of acute complicated type B aortic dissection". PMID- 26804228 TI - Pyridazinone substituted benzenesulfonamides as potent carbonic anhydrase inhibitors. AB - A series of sulfonamide derivatives (2a-l) incorporating substituted pyridazinone moieties were investigated for the inhibition of two human cytosolic carbonic anhydrase isoforms, hCA I and hCA II. All these compounds, together with the clinically used sulfonamide acetazolamide were investigated as inhibitors of the physiologically relevant isozymes I and II. These sulfonamides showed very strong inhibition against all these isoforms with K(I)'s in the range of 0.98-8.5 nM which makes such molecules possible to be used as leads for discovery of novel effective CA inhibitors targeting other isoforms with medicinal chemistry applications. PMID- 26804229 TI - Design and synthesis of novel 4'-demethyl-4-deoxypodophyllotoxin derivatives as potential anticancer agents. AB - A group of podophyllotoxin (PPT) derivatives (7a-j) were synthesized by conjugating aryloxyacetanilide moieties to the 4'-hydroxyl of 4'-demethyl-4 deoxypodophyllotoxin (DDPT), and their anticancer activity was evaluated. It was found that the most potent compound 7d inhibited the proliferation of three cancer cell lines with sub to low micromolar IC50 values. Furthermore, it was demonstrated that 7d induced cell cycle arrest in G2/M phase in MGC-803 cells, and regulated the expression of cell cycle check point proteins, such as cyclin A, cyclin B, CDK1, cdc25c, and p21. Finally, 4 mg/kg of 7d reduced the weights and volumes of HepG2 xenografts in mice. Our findings suggest that 7d might be a potential anticancer agent. PMID- 26804230 TI - Optimization of tetrahydronaphthalene inhibitors of Raf with selectivity over hERG. AB - Investigations of a biaryl ether scaffold identified tetrahydronaphthalene Raf inhibitors with good in vivo activity; however these compounds had affinity toward the hERG potassium channel. Herein we describe our work to eliminate this hERG activity via alteration of the substituents on the benzoic amide functionality. The resulting compounds have improved selectivity against the hERG channel, good pharmacokinetic properties and potently inhibit the Raf pathway in vivo. PMID- 26804231 TI - Design and synthesis of substituted pyrido[3,2-d]-1,2,3-triazines as potential Pim-1 inhibitors. AB - A novel series of substituted pyrido[3,2-d]-1,2,3-triazines were designed and synthesized as Pim-1 inhibitors through scaffold hopping. Most of the derivatives showed potent in vitro Pim-1 inhibitory activities and anti-proliferative effects toward prostate cancer cells. Among them, 6b, 6h and 6m showed the best Pim-1 inhibitory activity with IC50 values of 0.69, 0.60 and 0.80 MUM, respectively. Furthermore, compounds 6b, 6i, 6j and 6m showed strong inhibitory activity to human prostate cancer LNcap and PC-3 cell lines with IC50 values at low micromolar level. Structure-activity relationship analysis revealed that appropriate substitutions at C-6 positions contributed to the kinase inhibition and antiproliferative effects. Moreover, western blot assay suggested that 6j could decrease the levels of p-BAD and p-4E-BP1 in a dose-dependent manner in PC 3 cells. Docking studies showed that 3-N of the scaffold formed a hydrogen bond with Lys67, aromatic 4-aniline formed a key pi-pi stack with Phe49. Taken together, this study might provide the first sight for developing the pyrido[3,2 d]-1,2,3-triazine scaffold as novel Pim-1 inhibitors. PMID- 26804232 TI - Discovery of diamide compounds as diacylglycerol acyltransferase 1 (DGAT1) inhibitors. AB - Diamide compounds were identified as potent DGAT1 inhibitors in vitro, but their poor molecular properties resulted in low oral bioavailability, both systemically and to DGAT1 in the enterocytes of the small intestine, resulting in a lack of efficacy in vivo. Replacing an N-alkyl group on the diamide with an N-aryl group was found to be an effective strategy to confer oral bioavailability and oral efficacy in this lipophilic diamide class of inhibitors. PMID- 26804234 TI - Exploring the importance of zinc binding and steric/hydrophobic factors in novel HCV replication inhibitors. AB - Several novel compounds have been identified that inhibit the replication of hepatitis C virus in a replicon assay with EC50 values as low as 0.6 MUM. Lead compounds were modified to investigate the possible role that zinc binding may play in inhibitor efficacy. In addition, the structure-activity relationship was explored to increase inhibitor efficacy and possibly identify favorable interactions within the currently unknown inhibitor binding pocket. The rationale for inhibitor design and biological results are presented herein. PMID- 26804233 TI - Dissecting structure-activity-relationships of crebinostat: Brain penetrant HDAC inhibitors for neuroepigenetic regulation. AB - Targeting chromatin-mediated epigenetic regulation has emerged as a potential avenue for developing novel therapeutics for a wide range of central nervous system disorders, including cognitive disorders and depression. Histone deacetylase (HDAC) inhibitors have been pursued as cognitive enhancers that impact the regulation of gene expression and other mechanisms integral to neuroplasticity. Through systematic modification of the structure of crebinostat, a previously discovered cognitive enhancer that affects genes critical to memory and enhances synaptogenesis, combined with biochemical and neuronal cell-based screening, we identified a novel hydroxamate-based HDAC inhibitor, here named neurinostat, with increased potency compared to crebinostat in inducing neuronal histone acetylation. In addition, neurinostat was found to have a pharmacokinetic profile in mouse brain modestly improved over that of crebinostat. This discovery of neurinostat and demonstration of its effects on neuronal HDACs adds to the available pharmacological toolkit for dissecting the molecular and cellular mechanisms of neuroepigenetic regulation in health and disease. PMID- 26804235 TI - Rs895819 in MIR27A improves the predictive value of DPYD variants to identify patients at risk of severe fluoropyrimidine-associated toxicity. AB - The objective of this study was to determine whether genotyping of MIR27A polymorphisms rs895819A>G and rs11671784C>T can be used to improve the predictive value of DPYD variants to identify patients at risk of severe fluoropyrimidine associated toxicity (FP-toxicity). Patients treated previously in a prospective study with fluoropyrimidine-based chemotherapy were genotyped for rs895819 and rs11671784, and DPYD c.2846A>T, c.1679T>G, c.1129-5923C>G and c.1601G>A. The predictive value of MIR27A variants for early-onset grade >=3 FP-toxicity, alone or in combination with DPYD variants, was tested in multivariable logistic regression models. Random-effects meta-analysis was performed, including previously published data. A total of 1,592 patients were included. Allele frequencies of rs895819 and rs11671784 were 0.331 and 0.020, respectively. In DPYD wild-type patients, MIR27A variants did not affect risk of FP-toxicity (OR 1.3 for >=1 variant MIR27A allele vs. none, 95% CI: 0.87-1.82, p = 0.228). In contrast, in patients carrying DPYD variants, the presence of >=1 rs895819 variant allele was associated with increased risk of FP-toxicity (OR 4.9, 95% CI: 1.24-19.7, p = 0.023). Rs11671784 was not associated with FP-toxicity (OR 2.9, 95% CI: 0.47-18.0, p = 0.253). Patients carrying a DPYD variant and rs895819 were at increased risk of FP-toxicity compared to patients wild type for rs895819 and DPYD (OR 2.4, 95% CI: 1.27-4.37, p = 0.007), while patients with a DPYD variant but without a MIR27A variant were not (OR 0.3 95% CI: 0.06-1.17, p = 0.081). In meta-analysis, rs895819 remained significantly associated with FP-toxicity in DPYD variant allele carriers, OR 5.4 (95% CI: 1.83-15.7, p = 0.002). This study demonstrates the clinical validity of combined MIR27A/DPYD screening to identify patients at risk of severe FP-toxicity. PMID- 26804237 TI - DNA methylation levels of imprinted and nonimprinted genes DMRs associated with defective human spermatozoa. AB - Asthenozoospermia (AS) is a common cause of human male infertility. Recent studies have shown significant associations of aberrant DNA methylation in spermatozoa with male infertility. The aims of the this investigation were to assess the changes in DNA methylation of known imprinted genes (MEST, GNAS and H19), novel imprinted gene (FAM50B) and nonimprinted genes (LINE-1 and P16) DMRs in the spermatozoa of infertile men with single-factor AS. Semen samples were obtained from 46 AS patients and 49 age-matched normal controls. DNA methylation levels of detected genes DMR were determined by MassARRAY quantitative methylation analysis. The average methylation level at the P16 and MEST DMRs was significantly lower in AS patients than in controls (patients 6.51 +/- 0.32%, controls 7.66 +/- 0.40%, P < 0.01). The methylation level of 6 CpG sites of P16 DMR, and 1 CpG site of MEST, GNAS, FAM50B and LINE-1 DMRs, was lower in AS group than in control group. For the first time, the data presented here suggest that increased methylation defects of P16 DMR may be associated with low sperm motility. This study provides the potential association between low sperm motility infertile men and the aberrant DNA methylation of MEST, LINE-1, GNAS and FAM50B DMRs. PMID- 26804238 TI - Synthesis and Antimicrobial Activity of 4-Chloro-3-Nitrophenylthiourea Derivatives Targeting Bacterial Type II Topoisomerases. AB - A series of novel 4-chloro-3-nitrophenylthiourea derivatives were synthesized and evaluated for their antimicrobial, antibiofilm and tuberculostatic activities. Most of compounds exhibited high antibacterial activity against both standard and hospital strains (MIC values 0.5-2 MUg/mL), as compared to Ciprofloxacin. Derivatives with 3,4-dichlorophenyl (11) and 3-chloro-4-methylphenyl (13) substituents were the most promising towards Gram-positive pathogens. Both of them exhibited antibiofilm potency and effectively inhibited the formation of biofilms of methicillin-resistant and standard strains of Staphylococcus epidermidis. Two N-alkylthioureas (20, 21) showed twofold to fourfold increase in in vitro potency against isolates of Mycobacterium tuberculosis, as compared to Isoniazid. An action of 7, 10, 11, 13, 20 and 21 against activity of topoisomerases isolated from Staphylococcus aureus was studied. Synthesized compounds were found as non-genotoxic. PMID- 26804239 TI - Chromogranin A and other enteroendocrine markers in inflammatory bowel disease. AB - Changes in the distribution and products of enteroendocrine cells may play a role in immune activation and regulation of gut inflammation. This review aims at critically evaluating the main enteroendocrine markers in inflammatory bowel diseases (IBD). A narrative review was performed by searching inflammatory bowel diseases and enteroendocrine biomarkers in PubMed. Relevant modifications of some enteroendocrine markers, such as Chromogranin A, and their correlation with disease activity have been reported in patients with inflammatory bowel diseases. Even if data about neuroendocrine markers are sometimes contrasting, they may be potentially useful for the diagnosis and clinical management of these patients. PMID- 26804240 TI - Estrogen regulates excitatory amino acid carrier 1 (EAAC1) expression through sphingosine kinase 1 (SphK1) transacting FGFR-mediated ERK signaling in rat C6 astroglial cells. AB - Excitatory amino acid carrier 1 (EAAC1) is one important subtype of the excitatory amino acid transporters (EAATs), and its absence can increase the vulnerability to oxidative stress in neural tissue. Enhanced expression of EAAC1 can provide neuroprotection in multiple disorders, including ischemia and multiple sclerosis. However, the mechanism regulating EAAC1 expression is not fully understood. Using rat C6 astroglial cells, which specifically express EAAC1, we found that 17beta-estradiol (E2) and (+/-)-1-[(3aR(*),4S(*),9bS(*))-4 (6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8 yl]-ethanone (G1), an agonist of the G-protein-coupled estrogen receptor (GPR30), strongly increased EAAC1 protein levels and protected cells from hydrogen peroxide (H2O2) toxicity. We further found that E2/G1 activated sphingosine kinase 1 (SphK1) via GPR30, resulting in the transcription of fibroblast growth factor 2 (FGF2), which stimulated its receptor (FGFR) and led to the phosphorylation of FGFR substrate 2alpha (FRS2alpha). This triggered downstream ERK1/2 signaling for the expression of EAAC1. Both the knockdown of FGF2 by siRNA and the pharmacological suppression of the FGFR-ERK cascade abolished the E2/G1 effect on EAAC1 expression. Overall, our work characterizes a signaling pathway by which E2 transactivates FGFR-ERK to induce EAAC1 expression in an FGF2 dependent manner. This occurs through SphK1 activation via GPR30 and leads to a resistance to H2O2 toxicity. This signal transduction pathway may provide novel insights into our understanding of the neuroprotective effects of E2 and may reveal new therapeutic targets or drugs for regulating the oxidative toxicity effects of various neurological diseases. PMID- 26804241 TI - Postnatal development and sensory experience synergistically underlie the excitatory/inhibitory features of hippocampal neural circuits: Glutamatergic and GABAergic neurotransmission. AB - During a postnatal critical period balance of excitation/inhibition in the developing brain is highly regulated by environmental signals. Compared to the visual cortex, rare document includes effects of sensory experience on the hippocampus, which is also bombarded by sensory signals. In this study, basic and tetanized field excitatory postsynaptic potentials (fEPSPs) were recorded in CA1 area of hippocampus of light-(LR) and dark-reared (DR) rats (at 2, 4 and 6weeks of age). Also, we assessed age- and activity-dependent changes in the N-Methyl-d aspartic acid (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors subunit compositions and, GABA producing enzymes. While the sensory deprivation increased amplitude of baseline fEPSPs, it decreased degree of potentiation of post-tetanus responses. Expression of GluA1 and GluA2 subunits of AMPA receptors was increased across age in DR rats. In contrast to LR rats, mRNA and protein expression of GluN1, GluN2A and GluN2B subunits of NMDA receptors was decreased in DR ones. Also, dark rearing diminished expression of GABA synthesis enzymes GAD65 and GAD67. These results indicate that, sensory experience adjusts synaptic plasticity and might also affect the balance of excitation/inhibition in the hippocampus. PMID- 26804242 TI - Oct4 transcription factor in conjunction with valproic acid accelerates myelin repair in demyelinated optic chiasm in mice. AB - Multiple sclerosis is a demyelinating disease with severe neurological symptoms due to blockage of signal conduction in affected axons. Spontaneous remyelination via endogenous progenitors is limited and eventually fails. Recent reports showed that forced expression of some transcription factors within the brain converted somatic cells to neural progenitors and neuroblasts. Here, we report the effect of valproic acid (VPA) along with forced expression of Oct4 transcription factor on lysolecithin (LPC)-induced experimental demyelination. Mice were gavaged with VPA for one week, and then inducible Oct4 expressing lentiviral particles were injected into the lateral ventricle. After one-week induction of Oct4, LPC was injected into the optic chiasm. Functional remyelination was assessed by visual evoked potential (VEP) recording. Myelination level was studied using FluoroMyelin staining and immunohistofluorescent (IHF) against proteolipid protein (PLP). IHF was also performed to detect Oct4 and SSEA1 as pluripotency markers and Olig2, Sox10, CNPase and PDGFRalpha as oligodendrocyte lineage markers. One week after injection of Oct4 expressing vector, pluripotency markers SSEA1 and Oct4 were detected in the rims of the 3rd ventricle. LPC injection caused extensive demyelination and significantly delayed the latency of VEP wave. Animals pre-treated with VPA+Oct4 expressing vector, showed faster recovery in the VEP latency and enhanced myelination. Immunostaining against oligodendrocyte lineage markers showed an increased number of Sox10+ and myelinating cells. Moreover, transdifferentiation of some Oct4-transfected cells (GFP+ cells) to Olig2+ and CNPase+ cells was confirmed by immunostaining. One-week administration of VPA followed by one-week forced expression of Oct4 enhanced myelination by converting transduced cells to myelinating oligodendrocytes. This finding seems promising for enhancing myelin repair within the adult brains. PMID- 26804243 TI - The effect of urine storage on antiviral and antibiotic compounds in the liquid phase of source-separated urine. AB - The behaviour of pharmaceuticals related to the human immunodeficiency virus treatment was studied in the liquid phase of source-separated urine during six month storage at 20 degrees C. Six months is the recommended time for hygienization and use of urine as fertilizer. Compounds were spiked in urine as concentrations calculated to appear in urine. Assays were performed with separate compounds and as therapeutic groups of antivirals, antibiotics and anti tuberculotics. In addition, urine was amended either with faeces or urease inhibitor. The pharmaceutical concentrations were monitored from filtered samples with solid phase extraction and liquid chromatography. The concentration reductions of the studied compounds as such or with amendments ranged from less than 1% to more than 99% after six-month storage. The reductions without amendments were 41.9-99% for anti-tuberculotics; <52% for antivirals (except with 3TC 75.6%) and <50% for antibiotics. In assays with amendments, the reductions were all <50%. Faeces amendment resulted in similar or lower reduction than without it even though bacterial activity should have increased. The urease inhibitor prevented ureolysis and pH rise but did not affect pharmaceutical removal. In conclusion, removal during storage might not be enough to reduce risks associated with the studied pharmaceuticals, in which case other feasible treatment practises or urine utilization means should be considered. PMID- 26804244 TI - Downregulated DYRK2 expression is associated with poor prognosis and Oxaliplatin resistance in hepatocellular carcinoma. AB - We aimed to investigate the molecular mechanisms of DYRK2 and the HCC sensitivity to Oxaliplatin in DYRK2-depleted HCC cells. HCC tissue specimens were obtained from 86 HCC patients during hepatectomy. We used immunohistochemistry and western blot to analyze DYRK2 expression in HCC tissues and cell lines, and used siRNA transfection to decrease DYRK2 expression in HCC cells. Flow cytometry and CCK-8 assay were detected in cell cycle progression, cell proliferation and the efficacy of Oxaliplatin, DYRK2 was down-regulated in HCC tissues, compared with adjacent nontumor ones. The significant correlation between DYRK2 expression and clinicopathologic factors was apparently shown in the immunohistochemical and statistical analyses. The expression of DYRK2 was significantly associated with histological grade of HCC patients. Univariate and multivariate survival analyses revealed that DYRK2 was a significant predictor for overall survival of HCC patients. The depletion of DYRK2 promoted HCC cell proliferation, and increased resistance to Oxaliplatin. These data showed that the downregulated expression of DYRK2 in HCC tumor tissues could promote the proliferation of HCC cells. In addition, reducing DYRK2 expression was associated with poor prognosis and Oxaliplatin resistance in HCC. PMID- 26804246 TI - Thrombolytic Therapy as the Management of Mitral Transcatheter Valve-in-Valve Implantation Early Thrombosis. AB - A 70-year-old male underwent mitral transcatheter valve-in-valve implantation for a failed bioprosthesis implanted 11 years earlier. In the first days following the procedure, he developed thrombosis of the new bioprosthesis with restricted cusp motion. The transmitral mean gradient increased significantly despite effective anticoagulation therapy using unfractionated heparin infusion. Low dose and slow infusion of alteplase resulted in resolution of the thrombus and normalisation of cusp motion. Thereafter long-term anticoagulation using a vitamin K antagonist was instituted and the patient remained asymptomatic. PMID- 26804245 TI - Membrane potential shapes regulation of dopamine transporter trafficking at the plasma membrane. AB - The dopaminergic system is essential for cognitive processes, including reward, attention and motor control. In addition to DA release and availability of synaptic DA receptors, timing and magnitude of DA neurotransmission depend on extracellular DA-level regulation by the dopamine transporter (DAT), the membrane expression and trafficking of which are highly dynamic. Data presented here from real-time TIRF (TIRFM) and confocal microscopy coupled with surface biotinylation and electrophysiology suggest that changes in the membrane potential alone, a universal yet dynamic cellular property, rapidly alter trafficking of DAT to and from the surface membrane. Broadly, these findings suggest that cell-surface DAT levels are sensitive to membrane potential changes, which can rapidly drive DAT internalization from and insertion into the cell membrane, thus having an impact on the capacity for DAT to regulate extracellular DA levels. PMID- 26804247 TI - Effects of Continuous Positive Airway Pressure on Lipidaemia and High-sensitivity C-reactive Protein Levels in Non-obese Patients with Coronary Artery Disease and Obstructive Sleep Apnoea. AB - BACKGROUND: The effect of obesity and medication on the relationship between obstructive sleep apnoea (OSA) and lipidaemia and systemic inflammation is not fully understood for various reasons. The aim of the present study is to determine the effects of 12 months of therapy with continuous positive airway pressure (CPAP) on lipid profiles and high-sensitivity C-reactive protein (hs CRP) in non-obese patients with coronary artery disease (CAD) and OSA. METHODS: We consecutively recruited 78 non-obese subjects with newly diagnosed CAD and moderate-to-severe OSA who were taking lipid-lowering medication. Patients were randomised to CPAP treatment or the control group. The patients' lipids and the hs-CRP level were measured at baseline and at follow-up. RESULTS: Seventy patients completed the study. The CPAP and control groups had similar characteristics at baseline. The mean duration of CPAP treatment was 4.2+/ 1.1h/night. There was no significant difference in the lipids or hs-CRP levels at 12 months (both, P>0.05). The apnoea-hypopnoea index and Epworth Sleepiness Scale were significantly lower in the CPAP treatment group than in the control group (both, P<0.05). CONCLUSIONS: Continuous positive airway pressure treatment in non obese patients with CAD and OSA who are taking standardised lipid-lowering treatment does not significantly decrease the lipid or hs-CRP levels. In addition, there are no relationships found between the severity of OSA and the lipid profiles. However, the status of OSA and daytime sleepiness improved significantly in the CPAP group. CLINICAL TRIAL REGISTRATION NUMBER: URL: http://clinicaltrials.gov. Unique identifier: NCT02127177. PMID- 26804248 TI - Cisplatin resistance and opportunities for precision medicine. AB - Cisplatin is one of the most commonly used chemotherapy drugs, treating a wide range of cancer types. Unfortunately, many cancers initially respond to platinum treatment but when the tumor returns, drug resistance frequently occurs. Resistance to cisplatin is attributed to three molecular mechanisms: increased DNA repair, altered cellular accumulation, and increased drug inactivation. The use of precision medicine to make informed decisions on a patient's cisplatin resistance status and predicting the tumor response would allow the clinician to tailor the chemotherapy program based on the biology of the disease. In this review, key biomarkers of each molecular mechanism will be discussed along with the current clinical research. Additionally, known polymorphisms for each biomarker will be discussed in relation to their influence on cisplatin resistance. PMID- 26804249 TI - Inhalation of growth factors and apo-transferrin to protect and repair the hypoxic-ischemic brain. AB - Hypoxic-ischemic brain damage is a major contributor to chronic neurological dysfunction and acute mortality in infants as well as in adults. In this review, we summarize recent publications demonstrating that the intranasal administration (INA) of apo-transferrin (aTf) and different growth factors provides neuroprotection to the mouse and rat brain after a hypoxic-ischemic event. The intranasal delivery of growth factors such as insulin-like growth factor-1 (IGF 1) and vascular endothelial growth factor (VEGF) has been found to improve neurological function and reduce infarct size in adult rats after a hypoxic ischemic event. On the other hand, INA of aTf and epidermal growth factor (EGF) were effective in reducing white matter damage and inflammation and in promoting the proliferation and survival of oligodendroglial progenitor cells (OPCs) in a model of hypoxic-ischemic encephalopathy. Therefore, data summarized in this review suggest that INA of growth factors and aTf can be used in combination in clinical treatment in order to protect and repair the hypoxic-ischemic brain. PMID- 26804250 TI - Synoptic pharmacology: Detecting and assessing the pharmacological significance of ligands for orphan receptors. AB - This paper discusses the discovery of ligands for orphan receptors and the identification of the natural endogenous ligands for those receptors in physiology. The central thesis is that orphan seven transmembrane receptors (7TMRs) are allosteric conduits of chemical information exchange from extracellular ligands to intracellar signaling mechanisms. This being the case, the optimal systems for discovery of orphan ligands must be synoptic in nature, that is, include the allosteric co-binding species that interact with the receptor since this latter component is essential for normal orphan 7TMR function. Constitutively active orphan receptor systems are also discussed as useful testing systems for orphan ligands. This is because the activated orphan receptor has a heightened sensitivity to cellular signaling species and thus whole cell constitutively active systems become sensitive to ligand binding. Finally, the phenomenon of biased signaling (due to stabilization of unique receptor active conformations) is discussed as a roadblock to the definitive identification of the natural orphan ligand but not to the detection of ligand tools to elucidate orphan 7TMR function. PMID- 26804251 TI - Involvement of mast cells and proteinase-activated receptor 2 in oxaliplatin induced mechanical allodynia in mice. AB - The chemotherapeutic agent oxaliplatin induces neuropathic pain, a dose-limiting side effect, but the underlying mechanisms are not fully understood. Here, we show the potential involvement of cutaneous mast cells in oxaliplatin-induced mechanical allodynia in mice. A single intraperitoneal injection of oxaliplatin induced mechanical allodynia, which peaked on day 10 after injection. Oxaliplatin induced mechanical allodynia was almost completely prevented by congenital mast cell deficiency. The numbers of total and degranulated mast cells was significantly increased in the skin after oxaliplatin administration. Repetitive topical application of the mast cell stabilizer azelastine hydrochloride inhibited mechanical allodynia and the degranulation of mast cells without affecting the number of mast cells in oxaliplatin-treated mice. The serine protease inhibitor camostat mesilate and the proteinase-activated receptor 2 (PAR2) antagonist FSLLRY-NH2 significantly inhibited oxaliplatin-induced mechanical allodynia. However, it was not inhibited by the H1 histamine receptor antagonist terfenadine. Single oxaliplatin administration increased the activity of cutaneous serine proteases, which was attenuated by camostat and mast cell deficiency. Depletion of the capsaicin-sensitive primary afferents by neonatal capsaicin treatment almost completely prevented oxaliplatin-induced mechanical allodynia, the increase in the number of mast cells, and the activity of cutaneous serine proteases. These results suggest that serine protease(s) released from mast cells and PAR2 are involved in oxaliplatin-induced mechanical allodynia. Therefore, oxaliplatin may indirectly affect the functions of mast cells through its action on capsaicin-sensitive primary afferents. PMID- 26804253 TI - Prevalence and characteristics of spontaneous tinnitus in 11-year-old children. AB - OBJECTIVE: To estimate the prevalence of spontaneous tinnitus in 11-year-old children. DESIGN: A prospective UK population-based study. STUDY SAMPLE: A total of 7092 children from the Avon longitudinal study of parents and children (ALSPAC) who attended the hearing session at age 11 years and answered questions about tinnitus. RESULTS: We estimated the prevalence of any spontaneous tinnitus as 28.1% (95% CI 27.1, 29.2%), and the prevalence of 'clinically significant' tinnitus as 3.1% (95% CI 2.7, 3.5%). Children were less likely to have clinically significant tinnitus if the tinnitus was 'soft' rather than 'loud' and if continuous rather than intermittent. Clinical significance was more likely if the tinnitus occurred more than once a week. Neither pitch nor length of history were important determinants of clinical significance. Small increases in mean hearing threshold (of up to 2.3 dB HL) were associated with clinically significant tinnitus. CONCLUSIONS: Although the prevalence of any tinnitus in 11-year-old children appears high, the small proportion in which this was found to be clinically significant implies that this does not necessarily indicate a large unmet clinical demand. We would expect approximately one child per class of 30 to have clinically significant tinnitus which is, by definition, problematic. PMID- 26804252 TI - Stem Cells in the Limbal Stroma. AB - The corneal stroma contains a population of mesenchymal cells subjacent to the limbal basement membrane with characteristics of adult stem cells. These 'niche cells' support limbal epithelial stem cell viability. In culture by themselves, the niche cells display a phenotype typical of mesenchymal stem cells. These stromal stem cells exhibit a potential to differentiate to multiple cell types, including keratocytes, thus providing an abundant source of these rare cells for experimental and bioengineering applications. Stromal stem cells have also shown the ability to remodel pathological stromal tissue, suppressing inflammation and restoring transparency. Because stromal stem cells can be obtained by biopsy, they offer a potential for autologous stem cell treatment for stromal opacities. This review provides an overview of the status of work on this interesting cell population. PMID- 26804254 TI - AMPK signaling in skeletal muscle during exercise: Role of reactive oxygen and nitrogen species. AB - Reactive oxygen and nitrogen species (RONS) are generated during exercise depending on intensity, duration and training status. A greater amount of RONS is released during repeated high-intensity sprint exercise and when the exercise is performed in hypoxia. By activating adenosine monophosphate-activated kinase (AMPK), RONS play a critical role in the regulation of muscle metabolism but also in the adaptive responses to exercise training. RONS may activate AMPK by direct an indirect mechanisms. Directly, RONS may activate or deactivate AMPK by modifying RONS-sensitive residues of the AMPK-alpha subunit. Indirectly, RONS may activate AMPK by reducing mitochondrial ATP synthesis, leading to an increased AMP:ATP ratio and subsequent Thr(172)-AMPK phosphorylation by the two main AMPK kinases: LKB1 and CaMKKbeta. In presence of RONS the rate of Thr(172)-AMPK dephosphorylation is reduced. RONS may activate LKB1 through Sestrin2 and SIRT1 (NAD(+)/NADH.H(+)-dependent deacetylase). RONS may also activate CaMKKbeta by direct modification of RONS sensitive motifs and, indirectly, by activating the ryanodine receptor (Ryr) to release Ca(2+). Both too high (hypoxia) and too low (ingestion of antioxidants) RONS levels may lead to Ser(485)-AMPKalpha1/Ser(491) AMPKalpha2 phosphorylation causing inhibition of Thr(172)-AMPKalpha phosphorylation. Exercise training increases muscle antioxidant capacity. When the same high-intensity training is applied to arm and leg muscles, arm muscles show signs of increased oxidative stress and reduced mitochondrial biogenesis, which may be explained by differences in RONS-sensing mechanisms and basal antioxidant capacities between arm and leg muscles. Efficient adaptation to exercise training requires optimal exposure to pulses of RONS. Inappropriate training stimulus may lead to excessive RONS formation, oxidative inactivation of AMPK and reduced adaptation or even maladaptation. Theoretically, exercise programs should be designed taking into account the intrinsic properties of different skeletal muscles, the specific RONS induction and the subsequent signaling responses. PMID- 26804290 TI - Elastic Organic Crystals of a Fluorescent pi-Conjugated Molecule. AB - An elastic organic crystal of a pi-conjugated molecule has been fabricated. A large fluorescent single crystal of 1,4-bis[2-(4-methylthienyl)]-2,3,5,6 tetrafluorobenzene (over 1 cm long) exhibited a fibril lamella morphology based on slip-stacked molecular wires, and it was found to be a remarkably elastic crystalline material. The straight crystal was capable of bending more than 180 degrees under applied stress and then quickly reverted to its original shape upon relaxation. In addition, the fluorescence quantum yield of the crystal was about twice that of the compound in THF solution. Mechanical bending-relaxation resulted in reversible change of the morphology and fluorescence. This research offers a more general approach to flexible crystals as a promising new family of organic semiconducting materials. PMID- 26804288 TI - De novo biosynthesis of Gastrodin in Escherichia coli. AB - Gastrodin, a phenolic glycoside, is the key ingredient of Gastrodia elata, a notable herbal plant that has been used to treat various conditions in oriental countries for centuries. Gastrodin is extensively used clinically for its sedative, hypnotic, anticonvulsive and neuroprotective properties in China. Gastrodin is usually produced by plant extraction or chemical synthesis, which has many disadvantages. Herein, we report unprecedented microbial synthesis of gastrodin via an artificial pathway. A Nocardia carboxylic acid reductase, endogenous alcohol dehydrogenases and a Rhodiola glycosyltransferase UGT73B6 transformed 4-hydroxybenzoic acid, an intermediate of ubiquinone biosynthesis, into gastrodin in Escherichia coli. Pathway genes were overexpressed to enhance metabolic flux toward precursor 4-hydroxybenzyl alcohol. Furthermore, the catalytic properties of the UGT73B6 toward phenolic alcohols were improved through directed evolution. The finally engineered strain produced 545mgl(-1) gastrodin in 48h. This work creates a new route to produce gastrodin, instead of plant extractions and chemical synthesis. PMID- 26804291 TI - Optical coherence tomography (OCT) evaluation of intermediate coronary lesions in patients with NSTEMI. AB - INTRODUCTION: Coronary angiography is commonly performed following non-ST segment elevation myocardial infarction (NSTEMI) to assess the need for revascularization. Some of these patients have myocardial infarction (MI) with no obstructive coronary atherosclerosis (MINOCA). Patients without severe obstructive lesions are usually treated conservatively. However, coronary angiography has known limitations in the assessment of lesion severity. We report our experience of using coronary Optical Coherence Tomography (OCT) in a series of patients without severe obstructive coronary lesions. METHODS: 165 patients underwent coronary OCT at Vancouver General Hospital. NSTEMI was the clinical presentation in 70 patients and 26 had angiographically intermediate lesions with 40%-69% diameter stenosis. Prior to OCT image acquisition, intracoronary nitroglycerin 100-200MUg was administered. Blood in the vessel was displaced using contrast media by manual injections. RESULTS: OCT of the angiographically intermediate lesions showed larger minimal luminal area (MLA) than the angiographically severe lesions (MLA 3.3mm(2)+/-1.8mm(2) vs. 1.6mm(2)+/-0.6mm(2), p<0.001) and less severe % lumen area stenosis (54.2%+/-11.4% vs. 70.9%+/-6.8%, p=0.001). Plaque rupture or intracoronary thrombus was detected in 8/26 (31%) patients. PCI with stent deployment was performed in 16 patients (62%). CONCLUSION: In stabilized patients with NSTEMI and angiographically intermediate disease, OCT examination confirmed the lack of severe anatomical stenosis in most patients. However, OCT also identified coronary lesions with unstable features. Further research is needed to help guide management of this subgroup of patients. PMID- 26804293 TI - Parameter Sensitivity In Multivariate Methods. AB - Multivariate analyses are descriptive models of data. Interpreting the parameters of such models requires knowing how much the fit of the model to the data is impaired by changes in the parameters. The relation of parameter change to loss of goodness of fit can be called parameter sensitivity. Formulas are presented for assessing the sensitivity of multiple regression weights and principal component weights. PMID- 26804292 TI - Transradial bilateral common iliac ostial stenting using simultaneous hugging stent (SHS) technique. AB - Current literature has limited reports of iliac artery interventions performed via transradial approach (TRA). We report four successive cases of bilateral common iliac ostial stenting using simultaneous hugging stent (SHS) technique through bilateral TRA. This technique allows the patient and the operator to exploit the benefits of TRA while treating this complex substrate. PMID- 26804294 TI - A Comprehensive Trial Of The Scree And Kg Criteria For Determining The Number Of Factors. AB - In most well designed researches larger substantive factors show a break in size from those of a trivial lower degree of variance, which are due to error and other sources. The only short test for the number of such factors that has been repeatedly supported by plasmode results is the scree. The present experiment extends this empirical testing of the scree by taking 15 plasmodes, which vary in (1) number of variables, (2) of factors, (3) degree of obliquity, from orthogonal cases on, (4) presence of simple structure, (5) presence of error, extending to factoring random numbers, and (6) size of communality. The results support the scree and show it superior to the Kaiser-Guttman unity root criterion. Apart from the scree itself, a brief examination is made of the reliability of its use in the hands of trained and untrained judges. A second evaluation of the intrinsic validity of the scree is made by examining internal consistency of item and parcel factoring, of different sampling of variables and of change of population. The result again supports its capacity to locate the correct number of factors within narrow limits. PMID- 26804295 TI - Comparative Validity Of MMPI-168 Factors And Clinical Scales. AB - This study further explores the relative merits of MMPI factor scores versus clinical scale scores, using the MMPI results of a large unselected sample of public mental health patients and using mental status examination findings and clinical, diagnosis as criterion variables. Correlation of MMPI-168 factor scores, MMPI-168 estimated clinical scale scores and MMPI full scale clinical scores with mental status factor scores failed to evidence any clear advantage for any of the three MMPI variables. Similar findings were obtained for discriminant analysis "hit" rates, using clinical diagnosis as the prediction criterion. PMID- 26804296 TI - Comparative Validity Vs. Utility As Considerations In Personality Scale Construction. AB - The "best" strategy for personality scale construction may be a utilitarian concept rather than a psychometric one. Some specific suggestions are given. PMID- 26804297 TI - A Two-Group Classification Procedure For Multivariate Dichotomous Responses. AB - A two-group classification procedure for multivariate binary data is presented and discussed for the case of independent samples. The rule utilizes an orthogonal series expansion for state probabilities and introduces a method to achieve parsimony in modeling in accordance with a condition of optimality. In addition, the classification procedure gives a method for dealing with the difficult problem of sparseness, a condition which frequently causes problems in applying discrete methods to frequency data. PMID- 26804298 TI - Multivariate Analysis Of The Visual Information Processing Of Numbers. AB - This paper applies nonmetric multidimensional scaling and hierarchical clustering procedures to a confusion matrix of numbers. Two dimensions were interpreted "straight versus curved" and "locus of curvature," while four major clusters of numbers were developed. The results are applied to information processing as possible evidence of hierarchical structure in the pattern recognition of visual inputs. PMID- 26804299 TI - The Validity Of A Behavioral Rating Scale: Application Of A Psychophysical Technique. AB - A multidimensional scaling technique (MDS) was used to assess the content and construct validity of a behavioral rating scale constructed to measure appropriate and inappropriate classroom behavior. A group of teachers was asked to rate a number of videotaped samples of these two behavior categories. The MDS technique was used to construct the psychological maps or structures that the teachers used when making judgments about the behaviors. The structures are represented spatially and show the distance of each behavior from every other behavior and the fundamental properties of each group of behaviors. The results showed that the classroom behavior rating scale was generally a valid measure of students' classroom behavior on both content and construct validation measures. The majority of behaviors specified by the scale as inappropriate were judged by the teachers to be inappropriate, while all of the appropriate behaviors on the scale were considered valid by the teachers. Similarly the construct validity of the scale was confirmed by the teachers. They judged most of the scale-specified components of the construct labels "inappropriate" and "appropriate" as relevant and valid. The results suggest that MDS techniques represent a useful means of resolving complex problems of validity inherent in current methods of behavior analysis. PMID- 26804300 TI - Effect of intrahippocampal administration of anti-melanin-concentrating hormone on spatial food-seeking behavior in rats. AB - Melanin-concentrating hormone (MCH) is a hypothalamic peptide that plays a critical role in the regulation of food intake and energy metabolism. In this study, we investigated the potential role of dense hippocampal MCH innervation in the spatially oriented food-seeking component of feeding behavior. Rats were trained for eight sessions to seek food buried in an arena using the working memory version of the food-seeking behavior (FSB) task. The testing day involved a bilateral anti-MCH injection into the hippocampal formation followed by two trials. The anti-MCH injection did not interfere with the performance during the first trial on the testing day, which was similar to the training trials. However, during the second testing trial, when no food was presented in the arena, the control subjects exhibited a dramatic increase in the latency to initiate digging. Treatment with an anti-MCH antibody did not interfere with either the food-seeking behavior or the spatial orientation of the subjects, but the increase in the latency to start digging observed in the control subjects was prevented. These results are discussed in terms of a potential MCH-mediated hippocampal role in the integration of the sensory information necessary for decision-making in the pre-ingestive component of feeding behavior. PMID- 26804302 TI - ISAba1/blaOXA-23: A serious obstacle to controlling the spread and treatment of Acinetobacter baumannii strains. AB - This study demonstrated a direct correlation between Acinetobacter baumannii clusters carrying the ISAba1/blaOXA-23 gene and increased minimal inhibitory concentrations for carbapenems and greater clonal diversity. Our findings showed that clusters carrying ISAba1 are widely distributed in our hospital, further complicating the treatment and control of infections caused by A baumannii. PMID- 26804301 TI - Pneumocystis pneumonia outbreak among renal transplant recipients at a North American transplant center: Risk factors and implications for infection control. AB - BACKGROUND: Pneumocystis pneumonia is a severe opportunistic fungal infection. Outbreaks among renal transplant recipients have been reported in Europe and Japan, but never in North America. METHODS: We conducted a retrospective case control study among adult renal transplant recipients at a Canadian center, using a 3:1 matching scheme. Ten cases and 30 controls were matched based on initial transplantation date, and all patients received prophylaxis with trimethoprim sulfamethoxazole for 1 year posttransplantation. RESULTS: The median time between transplantation and infection was 10.2 years, and all patients survived. Compared with controls, case patients had statistically lower estimated glomerular filtration rate (29.3 mL/min vs 66.3 mL/min; P = .028) and lymphopenia (0.51 * 10(9)/L vs 1.25 * 10(9)/L; P = .002). Transmission mapping revealed significant overlap in the clinic and laboratory visits among case vs control patients (P = .0002). One hundred percent of patients (4 out of 4) successfully genotyped had the same strain of Pneumocystis jirovecii. CONCLUSIONS: Our study demonstrated an outbreak of pneumocystis more than 10 years following initial transplantation, despite using recommended initial prophylaxis. We identified low estimated glomerular filtration rate and lymphopenia as risk factors for infection. Overlapping ambulatory care visits were identified as important potential sources of infection transmission, suggesting that institutions should re-evaluate policy and infrastructure strategies to interrupt transmission of respiratory pathogens. PMID- 26804303 TI - Risk factors and outcomes of hospitalized patients with blood infections caused by multidrug-resistant Acinetobacter baumannii complex in a hospital of Northern China. AB - The purpose of this study was to determine the risk factors and outcomes of bloodstream infections caused by multidrug-resistant (MDR) Acinetobacter baumannii complex in a hospital of Northern China. Risk factors associated with MDR A baumannii complex included older age, pneumonia, using drainage catheters, and intensive care unit stay. Multivariate analysis showed that multidrug resistance and mechanical ventilation were identified as independent risk factors for 30-day mortality in patients with A baumannii complex bacteremia. PMID- 26804304 TI - An adenovirus 4 outbreak amongst staff in a pediatric ward manifesting as keratoconjunctivitis-a possible failure of contact and aerosol infection control. AB - An adenovirus serotype 4 outbreak was identified on a pediatric ward involving 4 members of the health care staff. Two inpatients on the ward at the time (1 immunocompromised) were shedding this virus from their respiratory tracts and could have acted as independent index cases for the staff infections. Significantly, upon investigation, it was found that staff members were unaware that adenoviruses are not completely eliminated by alcohol gel handrubs and that soap and water handwashing is also required. PMID- 26804305 TI - Relationship of various infection control interventions to the prevalence of multidrug-resistant Pseudomonas aeruginosa among U.S. hospitals. AB - BACKGROUND: Health care-associated infections caused by antibiotic-resistant gram negative bacteria, such as Pseudomonas aeruginosa, are an emerging and increasingly important public health threat. However, there are very few studies that examine the relationships between antimicrobial resistance strategies and interventions and the prevalence of antibiotic-resistant and multidrug-resistant strains of Pseudomonas. METHODS: The membership of the Association for Professionals in Infection Control and Epidemiology was invited to participate in a Web-based survey of U.S. acute care hospital infection preventionists. RESULTS: A final sample of 225 completed responses was analyzed using correlational techniques. Resistance to gentamicin (r = 0.17, P = .01), imipenem (r = 0.18, P = .02), ceftazidime (r = 0.20, P = .03), and ciprofloxacin (r = 0.15, P = .03) all showed significant direct associations with epidemiologic investigation using molecular testing. A significant inverse relationship was found between resistance to ceftazidime and effective efforts in the identification and isolation of infected patients (r = -0.18, P = .02). CONCLUSIONS: The finding of significant direct relationships between antimicrobial resistance and epidemiologic investigations using molecular testing suggests that the increased burden of resistance is associated with molecular testing rather than the intervention driving down rates. Effective identification and isolation of infected patients appeared to be associated with lower resistance rates. Further research is needed to uncover causal relationships. PMID- 26804306 TI - Infection surveillance systems in primary health care: A literature review. AB - The Patient Protection and Affordable Care Act of 2010 is placing primary care at the epicenter of accountability of US health care delivery. There is a significant body of evidence characterizing the value of acute-care hospital infection surveillance systems. Given the central role primary care is beginning to play, we were interested in examining the use of infection surveillance systems in primary care practice. Our review of the literature found only 2 articles describing the influence of primary care infection surveillance systems, both providing evidence of its benefits. This area is ripe for further research. PMID- 26804307 TI - Journal Club: Impact of rapid screening for discontinuation of methicillin resistant Staphylococcus aureus contact precautions. PMID- 26804310 TI - Wave-function frozen-density embedding: Approximate analytical nuclear ground state gradients. AB - We report the derivation of approximate analytical nuclear ground-state uncoupled frozen density embedding (FDEu) gradients for the resolution of identity (RI) variant of the second-order approximate coupled cluster singles and doubles (RICC2) as well as density functional theory (DFT), and an efficient implementation thereof in the KOALA program. In order to guarantee a computationally efficient treatment, those gradient terms are neglected which would require the exchange of orbital information. This approach allows for geometry optimizations of single molecules surrounded by numerous molecules with fixed nuclei at RICC2-in-RICC2, RICC2-in-DFT, and DFT-in-DFT FDE level of theory using a dispersion correction, required due to the DFT-based treatment of the interaction in FDE theory. Accuracy and applicability are assessed by the example of two case studies: (a) the Watson-Crick pair adenine-thymine, for which the optimized structures exhibit a maximum error of about 0.08 A for our best scheme compared to supermolecular reference calculations, (b) carbon monoxide on a magnesium oxide surface model, for which the error amount up to 0.1 A for our best scheme. Efficiency is demonstrated by successively including environment molecules and comparing to an optimized conventional supermolecular implementation, showing that the method is able to outperform conventional RICC2 schemes already with a rather small number of environment molecules, gaining significant speed up in computation time. PMID- 26804308 TI - Using medical student observers of infection prevention, hand hygiene, and injection safety in outpatient settings: A cross-sectional survey. AB - BACKGROUND: Health care-associated infection outbreaks have occurred in outpatient settings due to lapses in infection prevention. However, little is known about the overall infection prevention status in outpatient environments. METHODS: A cross-sectional design was employed to assess infection prevention policies and practices at 15 outpatient sites across New Mexico in 2014 during a medical student outpatient rotation. A standardized infection prevention checklist was completed via staff interview; observations of injection safety practices and hand hygiene behavior were conducted. Aggregate data were analyzed using Excel (Microsoft, Redmond, WA) and Stata (version 12.1, Stata Corp, College Station, TX) statistical software. RESULTS: Medical practice staff interviews reported a mean of 92.8% (median, 96.7%; range, 75.0%-98.9%) presence of recommended policies and practices. One hundred sixty-three injection safety observations were performed that revealed medication vial rubber septums were disinfected with alcohol 78.4% (95% confidence interval [CI], 71.1%-84.7%) of the time before piercing. Three hundred thirty hand hygiene observations revealed 33.9% (95% CI, 28.8%-39.1%) use of alcohol-based handrub, 29.1% (95% CI, 24.2% 34.0%) use of soap and water, and 37.0% (95% CI, 31.8%-42.4%) use of no hand hygiene. DISCUSSION AND CONCLUSION: These findings support the need for ongoing infection prevention quality improvement initiatives in outpatient settings and underscore the importance of assessing both self-report and observed behavior of infection prevention compliance. PMID- 26804312 TI - Role of nano-range amphiphilic polymers in seed quality enhancement of soybean and imidacloprid retention capacity on seed coatings. AB - BACKGROUND: Nano-size and wide-range solubility of amphiphilic polymers (having both hydrophilic and hydrophobic blocks) can improve uniformity in seed coatings. An investigation was carried out to assess the positive effect of amphiphilic polymers over hydrophilic or hydrophobic polymers as seed coating agents and pesticide carriers. RESULTS: Amphiphilic polymers with 127.5-354 nm micelle size were synthesized in the laboratory using polyethylene glycols and aliphatic di acids. After 6 months of storage, germination of uncoated soybean seeds decreased drastically from 97.80 to 81.55%, while polymer-coated seeds showed 89.44-95.92% germination. Similarly, vigour index-1 was reduced from 3841.10 to 2813.06 for control seeds but ranged from 3375.59 to 3844.60 for polymer-coated seeds after 6 months. The developed imidacloprid formulations retained more pesticide on soybean seed coatings than did a commercial formulation (Gaucho((r)) 600 FS). The time taken for 50% release of imidacloprid from seed coatings in water was 7.12 9.11 h for the developed formulations and 0.41 h for the commercial formulation. CONCLUSION: Nano-range amphiphilic polymers can be used to protect soybean seeds from ageing. Formulations as seed treatments may produce improved and sustained efficacy with minimum environmental contamination. (c) 2016 Society of Chemical Industry. PMID- 26804314 TI - A comparative molecular dynamics study on BACE1 and BACE2 flap flexibility. AB - Beta-amyloid precursor protein cleavage enzyme1 (BACE1) and beta-amyloid precursor protein cleavage enzyme2 (BACE2), members of aspartyl protease family, are close homologs and have high similarity in their protein crystal structures. However, their enzymatic properties are different, which leads to different clinical outcomes. In this study, we performed sequence analysis and all-atom molecular dynamic (MD) simulations for both enzymes in their ligand-free states in order to compare their dynamical flap behaviors. This is to enhance our understanding of the relationship between sequence, structure and the dynamics of this protein family. Sequence analysis shows that in BACE1 and BACE2, most of the ligand-binding sites are conserved, indicative of their enzymatic property as aspartyl protease members. The other conserved residues are more or less unsystematically localized throughout the structure. Herein, we proposed and applied different combined parameters to define the asymmetric flap motion; the distance, d1, between the flap tip and the flexible region; the dihedral angle, phi, to account for the twisting motion and the TriCalpha angle, theta2 and theta1. All four combined parameters were found to appropriately define the observed "twisting" motion during the flaps different conformational states. Additional analysis of the parameters indicated that the flaps can exist in an ensemble of conformations, i.e. closed, semi-open and open conformations for both systems. However, the behavior of the flap tips during simulations is different between BACE1 and BACE2. The BACE1 active site cavity is more spacious as compared to that of BACE2. The analysis of 10S loop and 113S loop showed a similar trend to that of flaps, with the BACE1 loops being more flexible and less stable than those of BACE2. We believe that the results, methods and perspectives highlighted in this report would assist researchers in the discovery of BACE inhibitors as potential Alzheimer's disease therapies. PMID- 26804318 TI - Diels-Alder Reactivities of Benzene, Pyridine, and Di-, Tri-, and Tetrazines: The Roles of Geometrical Distortions and Orbital Interactions. AB - The cycloadditions of benzene and ten different azabenzenes (pyridine, three diazines, three triazines, and three tetrazines) with the ethylene dienophile have been explored with density functional theory (M06-2X) and analyzed with the distortion/interaction model. Activation barriers correlate closely with both distortion energies and interaction energies over an activation energy range of 45 kcal/mol. The replacement of CH with N increases Diels-Alder reactivity due not only to the more favorable orbital interaction, but also to a decrease in distortion energy. The rates of reactions are greatly influenced by the nature of the bonds being formed: two C-C bonds > one C-C bond, and one C-N bond > two C-N bonds. The activation energy of Diels-Alder reactions correlates very well with reaction energies and with the NICS(0) values of the aromatic dienes. The distortion energy of the Diels-Alder reaction transition states mostly arises from the diene out-of-plane distortion energy. PMID- 26804311 TI - Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria. AB - Electronic (e)-cigarette use is rapidly rising, with 20 % of Americans ages 25-44 now using these drug delivery devices. E-cigarette users expose their airways, cells of host defense, and colonizing bacteria to e-cigarette vapor (EV). Here, we report that exposure of human epithelial cells at the air-liquid interface to fresh EV (vaped from an e-cigarette device) resulted in dose-dependent cell death. After exposure to EV, cells of host defense-epithelial cells, alveolar macrophages, and neutrophils-had reduced antimicrobial activity against Staphylococcus aureus (SA). Mouse inhalation of EV for 1 h daily for 4 weeks led to alterations in inflammatory markers within the airways and elevation of an acute phase reactant in serum. Upon exposure to e-cigarette vapor extract (EVE), airway colonizer SA had increased biofilm formation, adherence and invasion of epithelial cells, resistance to human antimicrobial peptide LL-37, and up regulation of virulence genes. EVE-exposed SA were more virulent in a mouse model of pneumonia. These data suggest that e-cigarettes may be toxic to airway cells, suppress host defenses, and promote inflammation over time, while also promoting virulence of colonizing bacteria. KEY MESSAGE: Acute exposure to e-cigarette vapor (EV) is cytotoxic to airway cells in vitro. Acute exposure to EV decreases macrophage and neutrophil antimicrobial function. Inhalation of EV alters immunomodulating cytokines in the airways of mice. Inhalation of EV leads to increased markers of inflammation in BAL and serum. Staphylococcus aureus become more virulent when exposed to EV. PMID- 26804321 TI - Mid-infrared optical parametric oscillators and frequency combs for molecular spectroscopy. AB - Nonlinear optical frequency conversion is one of the most versatile methods to generate wavelength-tunable laser light in the mid-infrared region. This spectral region is particularly important for trace gas detection and other applications of molecular spectroscopy, because it accommodates the fundamental vibrational bands of several interesting molecules. In this article, we review the progress of the most significant nonlinear optics instruments for widely tunable, high resolution mid-infrared spectroscopy: continuous-wave optical parametric oscillators and difference frequency generators. We extend our discussion to mid infrared optical frequency combs, which are becoming increasingly important spectroscopic tools, owing to their capability of highly sensitive and selective parallel detection of several molecular species. To illustrate the potential and limitations of mid-infrared sources based on nonlinear optics, we also review typical uses of these instruments in both applied and fundamental spectroscopy. PMID- 26804322 TI - Anesthetic considerations for patients with Bardet-Biedl syndrome: a case series and review of the literature. AB - BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare genetic condition with manifestations that can impact anesthetic and perioperative care. There is a void of literature describing the perioperative anesthetic management in this complex patient population. OBJECTIVES: The purpose of this retrospective series was to describe the perioperative care of patients diagnosed with BBS at a large academic tertiary referral center with experience in caring for these patients. METHODS: All patients receiving anesthesia during the time between July 10, 1997 and Jan 1, 2015 were identified. Anesthetic and perioperative records were reviewed in detail for demographic, echocardiographic, preoperative, intraoperative, and postoperative data. RESULTS: We identified 12 patients with BBS undergoing 40 anesthetics at our institution. The study identified a high risk for difficult airway with need for advanced airway techniques (67% of patient's >= 18 years of age required either awake fiberoptic or video laryngoscopy techniques), cardiac abnormalities, renal impairment, morbid obesity, and intellectual disability as the main syndrome manifestations of interest to the anesthesiologist. No patient had perioperative complications directly related to BBS; however, each underwent thorough perioperative evaluation with emphasis on the systemic comorbidities associated with the syndrome. This report illustrates that patients with BBS can safely undergo anesthesia, but a detailed and often multidisciplinary preoperative evaluation is prudent. PMID- 26804323 TI - Base-acid hybrid water electrolysis. AB - A base-acid hybrid electrolytic system with a low onset voltage of 0.78 V for water electrolysis was developed by using a ceramic Li-ion exchange membrane to separate the oxygen-evolving reaction (OER) in a basic electrolyte solution containing the Li-ion and hydrogen-evolving reaction (HER) in an acidic electrolyte solution. PMID- 26804325 TI - Efflux transporter engineering markedly improves amorphadiene production in Escherichia coli. AB - Metabolic engineering aims at altering cellular metabolism to produce valuable products at high yields and titers. Achieving high titers and productivity can be challenging if final products are largely accumulated intracellularly. A potential solution to this problem is to facilitate the export of these substances from cells by membrane transporters. Amorphadiene, the precursor of antimalarial drug artemisinin, is known to be secreted from Escherichia coli overexpressing the biosynthetic pathway. In order to assess the involvement of various endogenous efflux pumps in amorphadiene transport, the effects of single gene deletion of 16 known multidrug-resistant membrane efflux transporters were examined. The outer membrane protein TolC was found to be intimately involved in amorphadiene efflux. The overexpression of tolC together with ABC family transporters (macAB) or MFS family transporters (emrAB or emrKY) enhanced amorphadiene titer by more than threefold. In addition, the overexpression of transporters in the lipopolysaccharide transport system (msbA, lptD, lptCABFG) was found to improve amorphadiene production. As efflux transporters often have a wide range of substrate specificity, the multiple families of transporters were co-expressed and synergistic benefits were observed in amorphadiene production. This strategy of screening and then rationally engineering transporters can be used to improve the production of other valuable compounds in E. coli. Biotechnol. Bioeng. 2016;113: 1755-1763. (c) 2016 Wiley Periodicals, Inc. PMID- 26804326 TI - Controllable high-fidelity quantum state transfer and entanglement generation in circuit QED. AB - We propose a scheme to realize controllable quantum state transfer and entanglement generation among transmon qubits in the typical circuit QED setup based on adiabatic passage. Through designing the time-dependent driven pulses applied on the transmon qubits, we find that fast quantum sate transfer can be achieved between arbitrary two qubits and quantum entanglement among the qubits also can also be engineered. Furthermore, we numerically analyzed the influence of the decoherence on our scheme with the current experimental accessible systematical parameters. The result shows that our scheme is very robust against both the cavity decay and qubit relaxation, the fidelities of the state transfer and entanglement preparation process could be very high. In addition, our scheme is also shown to be insensitive to the inhomogeneous of qubit-resonator coupling strengths. PMID- 26804330 TI - Palladium-Catalyzed Trifluoromethylation of (Hetero)Arenes with CF3 Br. AB - The CF3 group is an omnipresent motif found in many pharmaceuticals, agrochemicals, catalysts, materials, and industrial chemicals. Despite well established trifluoromethylation methodologies, the straightforward and selective introduction of such groups into (hetero)arenes using available and less expensive sources is still a major challenge. In this regard, the selective synthesis of various trifluoromethyl-substituted (hetero)arenes by palladium catalyzed C-H functionalization is herein reported. This novel methodology proceeds under comparably mild reaction conditions with good regio- and chemoselectivity. As examples, trifluoromethylations of biologically important molecules, such as melatonin, theophylline, caffeine, and pentoxifylline, are showcased. PMID- 26804332 TI - Novel iminopyridine derivatives: ligands for preparation of Fe(ii) and Cu(ii) dinuclear complexes. AB - A series of imino- and amino-pyridine ligands based on dihydrobenzofurobenzofuran (BFBF) and methanodibenzodioxocine (DBDOC) backbones have been synthesized. These ligands form exclusively dinuclear complexes with metals such as iron(II) and copper(II). The structures for complexes 15, 16, 18, 19, 20, 21, 23, and 24 were determined by X-ray crystallography. The complexes show large distances for the metal nuclei and different geometries depending on the nature of the metal. An octahedral geometry was observed for the iron(II) complexes, while copper(II) complex 24 showed a distorted trigonal bipyramidal geometry. The iron(II) complexes showed activity as catalysts in the cycloaddition of CO2 to epoxides, obtaining moderate yields of cyclic carbonates. PMID- 26804327 TI - Involvement of spinal alpha2 -adrenoceptors in prolonged modulation of hind limb withdrawal reflexes following acute noxious stimulation in the anaesthetized rabbit. AB - The role of spinal alpha2 -adrenoceptors in mediating long-lasting modulation of hind limb withdrawal reflexes following acute noxious chemical stimulation of distant heterotopic and local homotopic locations has been investigated in pentobarbitone-anaesthetized rabbits. Reflexes evoked in the ankle extensor muscle medial gastrocnemius (MG) by electrical stimulation of the ipsilateral heel, and reflexes elicited in the ankle flexor tibialis anterior and the knee flexor semitendinosus by stimulation at the base of the ipsilateral toes, could be inhibited for over 1 h after mustard oil (20%) was applied to either the snout or into the contralateral MG. The heel-MG response was also inhibited after applying mustard oil across the plantar metatarsophalangeal joints of the ipsilateral foot, whereas this homotopic stimulus facilitated both flexor responses. Mustard oil also caused a significant pressor effect when applied to any of the three test sites. The selective alpha2 -adrenoceptor antagonist, RX 821002 (100-300 MUg, intrathecally), had no effect on reflexes per se, but did cause a decrease in mean arterial blood pressure. In the presence of the alpha2 blocker, inhibitory and facilitatory effects of mustard oil on reflexes were completely abolished. These data imply that long-lasting inhibition of spinal reflexes following acute noxious stimulation of distant locations involves activation of supraspinal noradrenergic pathways, the effects of which are dependent on an intact alpha2 -adrenoceptor system at the spinal level. These pathways and receptors also appear to be involved in facilitation (sensitization) as well as inhibition of reflexes following a noxious stimulus applied to the same limb. PMID- 26804333 TI - Common and differential alterations of general emotion processing in obsessive compulsive and social anxiety disorder. AB - BACKGROUND: Obsessive compulsive disorder (OCD) and social anxiety disorder (SAD) are characterized by biased perception and processing of potentially threatening stimuli. A hyper-reactivity of the fear-circuit [e.g. amygdala, anterior cingulate (ACC)] has been consistently reported using functional magnetic resonance imaging (fMRI) in SAD in comparison with healthy controls (HCs). Studies investigating the processing of specific emotional stimuli in OCD reported mainly orbitofrontal-striatal abnormalities. The goal of this study was to examine similar/common and differential neurobiological responses in OCD and SAD using unspecific emotional stimuli. METHOD: Fifty-four subjects participated: two groups (each n = 18) of outpatients with a current diagnosis of OCD or SAD, and 18 HCs. All subjects underwent fMRI while anticipating and perceiving unspecific visual stimuli with prior announced emotional valence (e.g. positive). RESULTS: Compared to HCs, the combined patient group showed increased activation in amygdala, caudate and prefrontal/orbitofrontal cortex while anticipating unspecific emotional stimuli. Caudate was more active in the combined patient group during perception. A comparison between the OCD and the SAD samples revealed increased amygdala and decreased rostral ACC activation in OCD patients during perception, but no differences in the anticipation phase. CONCLUSIONS: Overall, we could identify common fronto-subcortical hyper-reactivity in OCD and SAD while anticipating and perceiving unspecific emotional stimuli. While differential neurobiological responses between OCD and SAD when processing specific stimuli are evident from the literature, differences were less pronounced using unspecific stimuli. This could indicate a disturbance of emotion regulation common to both OCD and SAD. PMID- 26804334 TI - Minimally Invasive Supraorbital Key-hole Approach for the Treatment of Anterior Cranial Fossa Meningiomas. AB - The most important target of minimally invasive surgery is to obtain the best therapeutic effect with the least iatrogenic injury. In this background, a pivotal role in contemporary neurosurgery is played by the supraorbital key-hole approach proposed by Perneczky for anterior cranial base surgery. In this article, it is presented as a possible valid alternative to the traditional craniotomies in anterior cranial fossa meningiomas removal. From January 2008 to January 2012 at our department 56 patients underwent anterior cranial base meningiomas removal. Thirty-three patients were submitted to traditional approaches while 23 to supraorbital key-hole technique. A clinical and neuroradiological pre- and postoperative evaluation were performed, with attention to eventual complications, length of surgical procedure, and hospitalization. Compared to traditional approaches the supraorbital key-hole approach was associated neither to a greater range of postoperative complications nor to a longer surgical procedure and hospitalization while permitting the same lesion control. With this technique, minimization of brain exposition and manipulation with reduction of unwanted iatrogenic injuries, neurovascular structures preservation, and a better aesthetic result are possible. The supraorbital key-hole approach according to Perneckzy could represent a valid alternative to traditional approaches in anterior cranial base meningiomas surgery. PMID- 26804335 TI - Organic devices based on nickel nanowires transparent electrode. AB - Herein, we demonstrate a facile approach to synthesize long nickel nanowires and discuss its suitability to replace our commonly used transparent electrode, indium-tin-oxide (ITO), by a hydrazine hydrate reduction method where nickel ions are reduced to nickel atoms in an alkaline solution. The highly purified nickel nanowires show high transparency within the visible region, although the sheet resistance is slightly larger compared to that of our frequently used transparent electrode, ITO. A comparison study on organic light emitting diodes and organic solar cells, using commercially available ITO, silver nanowires, and nickel nanowires, are also discussed. PMID- 26804337 TI - Anderson localization of light in a colloidal suspension (TiO2@silica). AB - In recent years, there has been dramatic progress in the photonics field in disordered media, ranging from applications in solar collectors, photocatalyzers, random lasing, and other novel photonic functions, to investigations into fundamental topics, such as light confinement and other phenomena involving photon interactions. This paper reports several pieces of experimental evidence of localization transition in a strongly disordered scattering medium composed of a colloidal suspension of core-shell nanoparticles (TiO2@silica) in ethanol solution. We demonstrate the crossover from a diffusive transport to a localization transition regime as the nanoparticle concentration is increased, and that an enhanced absorption effect arises at localization transition. PMID- 26804339 TI - Case study of evaluations that go beyond clinical outcomes to assess quality improvement diabetes programmes using the Diabetes Evaluation Framework for Innovative National Evaluations (DEFINE). AB - RATIONALE, AIMS AND OBJECTIVES: Investments in efforts to reduce the burden of diabetes on patients and health care are critical; however, more evaluation is needed to provide evidence that informs and supports future policies and programmes. The newly developed Diabetes Evaluation Framework for Innovative National Evaluations (DEFINE) incorporates the theoretical concepts needed to facilitate the capture of critical information to guide investments, policy and programmatic decision making. The aim of the study is to assess the applicability and value of DEFINE in comprehensive real-world evaluation. METHOD: Using a critical and positivist approach, this intrinsic and collective case study retrospectively examines two naturalistic evaluations to demonstrate how DEFINE could be used when conducting real-world comprehensive evaluations in health care settings. RESULTS: The variability between the cases and the evaluation designs are described and aligned to the DEFINE goals, steps and sub-steps. The majority of the theoretical steps of DEFINE were exemplified in both cases, although limited for knowledge translation efforts. Application of DEFINE to evaluate diverse programmes that target various chronic diseases is needed to further test the inclusivity and built-in flexibility of DEFINE and its role in encouraging more comprehensive knowledge translation. CONCLUSIONS: This case study shows how DEFINE could be used to structure or guide comprehensive evaluations of programmes and initiatives implemented in health care settings and support scale up of successful innovations. Future use of the framework will continue to strengthen its value in guiding programme evaluation and informing health policy to reduce the burden of diabetes and other chronic diseases. PMID- 26804340 TI - Comparing the short-term outcomes of laparoscopic distal gastrectomy with D1+ and D2 lymph node dissection for gastric cancer. AB - INTRODUCTION: Laparoscopic distal gastrectomy (LDG) with D1+ lymph node dissection (LND) for early gastric cancer has been widely accepted. However, LDG with D2 LND for advanced gastric cancer remains in limited use. The aim of this retrospective study was to clarify the safety of LDG with D2 LND for gastric cancer. METHODS: From January 2010 to September 2014, 296 patients underwent LDG; those who received D1+ LND (n = 230) or D2 LND (n = 66) were included in this study. The clinicopathological characteristics and short-term outcomes of both groups were investigated and compared. RESULTS: There were no significant differences in the incidence of postoperative complications between the two groups. However, the frequency of infectious intra-abdominal complications was higher in the D2 LND group than in the D1+ LND group. Additionally, a lower risk of infectious intra-abdominal complications was seen with certified than with uncertified operators. CONCLUSION: The evaluation of short-term outcomes demonstrated that LDG with D2 LND is generally feasible. However, the risk of infectious intra-abdominal complications is higher with D2 LND than with D1+ LND. Also, D2 LND should be performed by trained operators. PMID- 26804338 TI - beta-Adrenergic Control of Hippocampal Function: Subserving the Choreography of Synaptic Information Storage and Memory. AB - Noradrenaline (NA) is a key neuromodulator for the regulation of behavioral state and cognition. It supports learning by increasing arousal and vigilance, whereby new experiences are "earmarked" for encoding. Within the hippocampus, experience dependent information storage occurs by means of synaptic plasticity. Furthermore, novel spatial, contextual, or associative learning drives changes in synaptic strength, reflected by the strengthening of long-term potentiation (LTP) or long-term depression (LTD). NA acting on beta-adrenergic receptors (beta-AR) is a key determinant as to whether new experiences result in persistent hippocampal synaptic plasticity. This can even dictate the direction of change of synaptic strength.The different hippocampal subfields play different roles in encoding components of a spatial representation through LTP and LTD. Strikingly, the sensitivity of synaptic plasticity in these subfields to beta-adrenergic control is very distinct (dentate gyrus > CA3 > CA1). Moreover, NA released from the locus coeruleus that acts on beta-AR leads to hippocampal LTD and an enhancement of LTD-related memory processing. We propose that NA acting on hippocampal beta-AR, that is graded according to the novelty or saliency of the experience, determines the content and persistency of synaptic information storage in the hippocampal subfields and therefore of spatial memories. PMID- 26804342 TI - Accurate Prediction of Contact Numbers for Multi-Spanning Helical Membrane Proteins. AB - Prediction of the three-dimensional (3D) structures of proteins by computational methods is acknowledged as an unsolved problem. Accurate prediction of important structural characteristics such as contact number is expected to accelerate the otherwise slow progress being made in the prediction of 3D structure of proteins. Here, we present a dropout neural network-based method, TMH-Expo, for predicting the contact number of transmembrane helix (TMH) residues from sequence. Neuronal dropout is a strategy where certain neurons of the network are excluded from back propagation to prevent co-adaptation of hidden-layer neurons. By using neuronal dropout, overfitting was significantly reduced and performance was noticeably improved. For multi-spanning helical membrane proteins, TMH-Expo achieved a remarkable Pearson correlation coefficient of 0.69 between predicted and experimental values and a mean absolute error of only 1.68. In addition, among those membrane protein-membrane protein interface residues, 76.8% were correctly predicted. Mapping of predicted contact numbers onto structures indicates that contact numbers predicted by TMH-Expo reflect the exposure patterns of TMHs and reveal membrane protein-membrane protein interfaces, reinforcing the potential of predicted contact numbers to be used as restraints for 3D structure prediction and protein-protein docking. TMH-Expo can be accessed via a Web server at www.meilerlab.org . PMID- 26804344 TI - Crisponi/CISS1 syndrome: A case series. AB - Crisponi/CISS1 syndrome (MIM#272430) is a rare autosomal recessive disease characterized by major feeding difficulties, camptodactyly, and anhidrosis in early childhood; and the subsequent development of paradoxical cold-induced sweating and scoliosis later in life. The syndrome is caused by biallelic mutations in CRLF1 or, much less commonly, CLCF1. Although genotype/phenotype correlation has been elusive, it has been suggested that the level of the mutant protein may correlate with the phenotypic severity. However, we show in this series of 12 patients from four families, all previously unpublished, that the homogeneity of the recently described c.983dupG (p.Ser328Argfs*2) mutation in CRLF1 was associated with a highly variable degree of severity, and that the phenotype significantly overlaps with the recently described COG6-related anhidrosis syndrome (MIM#615328). Another fifth previously unpublished family is also described with a novel mutation in CRLF1, c.605delC (p.Ala202Valfs*32). In Saudi Arabia the prevalence of the syndrome is probably underestimated due to the difficulty in making the diagnosis considering the complex phenotype with typical neonatal and evolutive features. PMID- 26804343 TI - Breaking sarcomeres by in vitro exercise. AB - Eccentric exercise leads to focal disruptions in the myofibrils, referred to as "lesions". These structures are thought to contribute to the post-exercise muscle weakness, and to represent areas of mechanical damage and/or remodelling. Lesions have been investigated in human biopsies and animal samples after exercise. However, this approach does not examine the mechanisms behind lesion formation, or their behaviour during contraction. To circumvent this, we used electrical pulse stimulation (EPS) to simulate exercise in C2C12 myotubes, combined with live microscopy. EPS application led to the formation of sarcomeric lesions in the myotubes, resembling those seen in exercised mice, increasing in number with the time of application or stimulation intensity. Furthermore, transfection with an EGFP-tagged version of the lesion and Z-disc marker filamin-C allowed us to observe the formation of lesions using live cell imaging. Finally, using the same technique we studied the behaviour of these structures during contraction, and observed them to be passively stretching. This passive behaviour supports the hypothesis that lesions contribute to the post-exercise muscle weakness, protecting against further damage. We conclude that EPS can be reliably used as a model for the induction and study of sarcomeric lesions in myotubes in vitro. PMID- 26804345 TI - It's an honour. Optometry in the Order of Australia. PMID- 26804347 TI - A framework for the assessment of the spatial and temporal patterns of threatened coastal delphinids. AB - The massively accelerated biodiversity loss rate in the Anthropocene calls for an efficient and effective way to identify the spatial and temporal dynamics of endangered species. To this end, we developed a useful identification framework based on a case study of locally endangered Sousa chinensis by combining both LEK (local ecological knowledge) evaluation and regional boat-based survey methods. Our study investigated the basic ecological information of Sousa chinensis in the estuaries of eastern Guangdong that had previously been neglected, which could guide the future study and conservation. Based on the statistical testing of reported spatial and temporal dolphins sighting data from fishermen and the ecological monitoring analyses, including sighting rate, site fidelity and residence time estimations, some of the current Sousa chinensis units are likely to be geographically isolated and critically endangered, which calls for much greater conservation efforts. Given the accelerated population extinction rate and increasing budgetary constraints, our survey pattern can be applied in a timely and economically acceptable manner to the spatial and temporal assessment of other threatened coastal delphinids, particularly when population distributions are on a large scale and traditional sampling methods are difficult to implement. PMID- 26804349 TI - Risk factors for fatal outcome in surgical patients with postoperative aspiration pneumonia. AB - INTRODUCTION: Aspiration pneumonia in hospitalized surgical patients has been associated with a mortality of approximately 30%. The aim of this study was to assess pre-, intra- and postoperative risk factors for mortality in patients suffering aspiration pneumonia after abdominal surgery. METHODS: Retrospective study from 01/2006-12/2012 of patients with clinically and radiologically confirmed aspiration pneumonia after abdominal surgery. RESULTS: A total of 70 patients undergoing abdominal surgery and postoperative aspiration pneumonia were identified. There were 53 (76%) male patients, the mean age was 71 +/- 12 years and the mean ASA score was 3 +/- 1. The surgical procedures included 32 colorectal or small bowel resections, 10 partial liver resections, 9 gastric surgeries, 8 esophageal resections, 5 pancreatic surgeries, and 6 hernia repairs. Aspiration pneumonia occurred at mean postoperative day 7 +/- 10. Overall, 53% (n = 37) of patients required re-intubation, with 4 +/- 5 days of additional mechanical ventilation. Mean hospital and ICU length of stay was 32 +/- 25 days and 6 +/- 9 days, respectively. Overall mortality was 27% (n = 19). Forward logistic regression revealed older age [OR 7.41 (95% CI: 1.29-42.62)], bilateral aspiration pneumonia [OR 7.39 (95% CI: 1.86-29.29)] and intraoperative requirement of blood component transfusion [OR 5.09 (95% CI: 1.34-19.38)] as independent risk factors for mortality (overall R(2) = 0.336). CONCLUSION: Postoperative aspiration pneumonia remains a severe complication with significant mortality. Increasing age, the need for intraoperative blood component transfusion and bilateral pulmonary infiltrates are independent risk factors for fatal outcome after aspiration pneumonia. Therefore, these patients suffering aspiration pneumonia require special attention and increased monitoring. PMID- 26804350 TI - Improving the quality of operative notes for laparoscopic cholecystectomy: Assessing the impact of a standardized operation note proforma. AB - INTRODUCTION: Operative notes are the recognized standard for documenting the details of an operation yet key procedural details are frequently missing. With the aim of improving standards, based on the Royal College of Surgeons (RCS) and Dutch Society of Surgery (DSS) Guidelines, we introduced an operation note proforma for use following laparoscopic cholecystectomy in a tertiary centre in the UK. METHODS: This study audited 130 consecutive laparoscopic cholecystectomy operation notes against accepted guidelines across three hospital sites within the same NHS Trust. Following analysis of these operation notes a standardized operation note proforma was designed and introduced across the Trust, which included all items from the DSS and RCS guidelines in the form of keyword prompts or simple yes/no responses. A further 128 operation notes were analysed. Guideline compliance was compared pre- and post-introduction of the proforma. Non parametric data were analysed using Fisher's exact and Mann-Whitney U tests. Statistical significance was set at p < 0.05. RESULTS: On a global assessment of operation note completeness against all guideline items, introduction of an operation note proforma significantly improved documentation rates for both DSS guidelines (p < 0.001) and RCS guidelines (p < 0.001). DISCUSSION: We have demonstrated that the introduction of a procedure-specific proforma to assist with writing the post-operative note following laparoscopic cholecystectomy can result in significant improvements in documentation of generic and procedure specific items that should be recorded for every operation. Procedure-specific proformas, based on established guidelines can help to produce more complete and medico-legally robust operation notes. PMID- 26804351 TI - High patency of proximal splenorenal shunt: A myth or reality ? - A prospective cohort study. AB - BACKGROUND: Proximal splenorenal shunt (PSRS) is a well-accepted surgical procedure for non-cirrhotic portal hypertension (NCPH). Though a patent shunt is important for good long term outcome, there are very few studies on patency of these shunts. We analysed shunt patency using dynamic computed tomographic (CT) portography and compared it with other modalities. METHODS: From 2004 to 2014, 50 patients with PSRS were evaluated prospectively for shunt patency using dynamic CT portography, clinical parameters and ultrasound Doppler. RESULTS: The causes of NCPH were extrahepatic portal vein obstruction (EHPVO) in 38 patients and non cirrhotic portal fibrosis (NCPF) in 12 patients. The shunt patency rate using clinical parameters, ultrasound Doppler and dynamic CT portography were 70%, 40% and 60% respectively. Clinical parameters overestimated while ultrasound Doppler underestimated the shunt patency rate. Dynamic portography had 100% correlation with conventional angiography in the five patients when this was done. The site of shunt could be demonstrated convincingly by dynamic CT portography. The shunt patency rate decreased over time. It was 64%, 60% and 43% in <1 year, 1-5 years and >5 years respectively. Our NCPF patients had a greater shunt patency rate compared to EHPVO patients (9/12 vs. 21/38) though the difference was not significant. Only size of the splenic vein had a significant impact on the shunt patency rate on statistical analysis. CONCLUSIONS: Dynamic CT portography is useful for evaluation of shunt patency. Proximal splenorenal shunts have a high blockage rate which has hitherto not been reported. PMID- 26804352 TI - Ileal versus sigmoid neobladder as bladder substitute after radical cystectomy for bladder cancer: A meta-analysis. AB - PURPOSE: To evaluate and compare the functional outcomes of ileal and sigmoid neobladders in patients underwent radical cystectomy. METHODS: Relevant studies were identified by searching PubMed, Embase, and Cochrane Library. The studies comparing the functional outcomes of sigmoid neobladder (SN) and ileal neobladder (IN) in patients underwent radical cystectomy were included. RESULTS: A total of 12 cohort studies were included in this meta-analysis. From our analysis, more early complications were observed in SN group than in IN group (RR = 1.37, 95% CI: 1.03-1.81). Both daytime and nighttime continence rates were significantly better in IN group than in SN group (RR = 0.87, 95%CI: 0.81-0.94) (RR = 0.73, 95%CI: 0.60-0.90). More patients could spontaneous voiding in SN group than in IN group (RR = 1.12, 95%CI: 1.00-1.26). According to the urodynamic study, ileal neobladder exhibited bigger capacity (WMD = -84.93, 95%CI: -160.36 to -9.50), lower pressure at capacity (WMD = 11.18, 95%CI: 4.29-18.06), better compliance (WMD = -25.55, 95%CI: -32.45 to -18.64), and greater post-void residual volume(WMD = -23.48, 95%CI: -36.75 to -10.21); There was no significant difference in the max voiding flow rate or void volume between the two groups (WMD = -1.00, 95%CI: -3.73-1.73) (WMD = -27.00, 95%CI: 70.05-16.06). No significant difference was found in the serum creatinine between the two groups (WMD = -0.05, 95%CI: -0.12-0.03). CONCLUSIONS: Ileal neobladder seems able to provide more favorable patient's satisfaction, while sigmoid neobladder may provide a better chance of spontaneous voiding. This meta-analysis may provide some useful evidences for urological surgeons to choose the ideal bladder substitute for patients underwent radical cystectomy. PMID- 26804353 TI - Approaches to optimize focused extracorporeal shockwave therapy (ESWT) based on an observational study of 363 feet with recalcitrant plantar fasciitis. AB - INTRODUCTION: Extracorporeal shockwave therapy (ESWT) is an established second line treatment option for plantar fasciitis. Longer term results of focused ESWT are rare in literature. This study assessed the treatment success-rates of single session ESWT compared to repetitive ESWT treatment sessions, the mid-term results as well as treatment- or patient-related factors influencing the outcome of focused ESWT for plantar fasciitis. METHODS: 284 patients (363 feet) received ESWT for plantar fasciitis and answered a questionnaire on socio-demographic and anamnestic data immediately before as well as 19-77 weeks after the first application of ESWT. RESULTS: 76 percent of patients treated only once and 74 percent of all patients reported satisfying pain relief (with up to three treatment sessions). This was consistent in the mid-term and over different physicians as well as independent of assessed patient- or treatment-related factors. DISCUSSION: Applying repeated ESWT in weekly intervals by default may be helpful in reducing healing time for those patients requiring more than one treatment session. Prospective research is needed to find out whether further treatment sessions are justifiable in patients who indicate no improvement after two or three treatment sessions. CONCLUSIONS: In many cases, focused ESWT needs to be applied only once. Further research should focus on the number of treatment sessions as well as the minimum energy flux density needed. PMID- 26804354 TI - Anterior versus posterior approach for the treatment of cervical compressive myelopathy due to ossification of the posterior longitudinal ligament: A systematic review and meta-analysis. AB - PURPOSE: The purpose of the study is to perform a systematic review and meta analysis to evaluate the clinical results of anterior and posterior approaches for the treatment of cervical compressive myelopathy due to cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: Randomized controlled trials or non-randomized controlled trials published since January 1995 to October 2015 that compared the clinical effectiveness of anterior and posterior surgical approaches for the treatment of cervical OPLL were acquired by a comprehensive search in three electronic databases (PubMed, EMBASE, Cochrane library). A total of 13 studies (1050 patients) were included in this systematic review and meta-analysis. RESULT: The results indicated that no statistically significant differences between the anterior group and posterior group in terms of preoperative JOA score [P = 0.16, SMD = 0.1 (-0.04, 0.23)] and recovery rate of patients with canal-occupying ratio < 50%-60% [p = 0.89, SMD = 0.03 (-0.35, 0.41)]. The anterior group showed higher postoperative JOA score [P < 0.05, SMD = 0.23 (0.05, 0.41)], overall recovery rate (regardless of canal-occupying ratio) [P < 0.01, SMD = 0.79 (0.31, 1.27)], especially a significant higher recovery rate of patients with canal-occupying ratio > 50%-60% [P < 0.01, SMD = 1.50 (0.52, 2.47)]. However, it also revealed that the postoperative complication rate [P < 0.05, OR = 1.90 (1.08, 3.36)], blood loss [P < 0.01, SMD = 0.63 (0.34, 0.93)] and operative time [P < 0.01, SMD = 1.86 (1.07, 2.65)] were significantly higher. CONCLUSION: Based on the results above, anterior approach surgery was associated with better overall (regardless of the canal-occupying ratio) postoperative neural function than posterior approach in the treatment of cervical compressive myelopathy due to OPLL. We thought anterior approach especially preferable to patients with canal-occupying ratio > 50%-60%, although it leads to a higher surgical trauma and incidence of surgery-related complications. Posterior approach surgery was relatively safer with lower surgical trauma and incidence of complications. We also suggest posterior approach for patients with canal-occupying ratio < 50%-60%, since the postoperative neural function was similar between the two groups for this part of patients. PMID- 26804355 TI - Hemispheric Asymmetry of Endogenous Neural Oscillations in Young Children: Implications for Hearing Speech In Noise. AB - Speech signals contain information in hierarchical time scales, ranging from short-duration (e.g., phonemes) to long-duration cues (e.g., syllables, prosody). A theoretical framework to understand how the brain processes this hierarchy suggests that hemispheric lateralization enables specialized tracking of acoustic cues at different time scales, with the left and right hemispheres sampling at short (25 ms; 40 Hz) and long (200 ms; 5 Hz) periods, respectively. In adults, both speech-evoked and endogenous cortical rhythms are asymmetrical: low frequency rhythms predominate in right auditory cortex, and high-frequency rhythms in left auditory cortex. It is unknown, however, whether endogenous resting state oscillations are similarly lateralized in children. We investigated cortical oscillations in children (3-5 years; N = 65) at rest and tested our hypotheses that this temporal asymmetry is evident early in life and facilitates recognition of speech in noise. We found a systematic pattern of increasing leftward asymmetry for higher frequency oscillations; this pattern was more pronounced in children who better perceived words in noise. The observed connection between left-biased cortical oscillations in phoneme-relevant frequencies and speech-in-noise perception suggests hemispheric specialization of endogenous oscillatory activity may support speech processing in challenging listening environments, and that this infrastructure is present during early childhood. PMID- 26804356 TI - Achieving High-Quality Multicultural Geriatric Care. AB - As the ethnic diversity of the U.S. population increases, there is a growing awareness of healthcare disparities and the need to address them. This position statement that the American Geriatrics Society (AGS) Ethnogeriatrics Committee developed outlines healthcare disparities in the United States and the minimum quality indicators that healthcare organizations and healthcare providers should adopt to ensure that all older adults receive care that is culturally appropriate and takes into account level of health literacy. PMID- 26804357 TI - Foreword: Health Economic Evaluations in Low- and Middle-income Countries: Methodological Issues and Challenges for Priority Setting. PMID- 26804358 TI - Editorial. PMID- 26804359 TI - Economic Evaluation in Global Perspective: A Bibliometric Analysis of the Recent Literature. AB - We present a bibliometric analysis of recently published full economic evaluations of health interventions and reflect critically on the implications of our findings for this growing field. We created a database drawing on 14 health, economic, and/or general literature databases for articles published between 1 January 2012 and 3 May 2014 and identified 2844 economic evaluations meeting our criteria. We present findings regarding the sensitivity, specificity, and added value of searches in the different databases. We examine the distribution of publications between countries, regions, and health areas studied and compare the relative volume of research with disease burden. We analyse authors' country and institutional affiliations, journals and journal type, language, and type of economic evaluation conducted. More than 1200 economic evaluations were published annually, of which 4% addressed low-income countries, 4% lower-middle-income countries, 14% upper-middle-income countries, and 83% high-income countries. Across country income levels, 53, 54, 86, and 100% of articles, respectively, included an author based in a country within the income level studied. Biomedical journals published 74% of economic evaluations. The volume of research across health areas correlates more closely with disease burden in high-income than in low-income and middle-income countries. Our findings provide an empirical basis for further study on methods, research prioritization, and capacity development in health economic evaluation. PMID- 26804360 TI - Outcomes in Economic Evaluations of Public Health Interventions in Low- and Middle-Income Countries: Health, Capabilities and Subjective Wellbeing. AB - Public health programmes tend to be complex and may combine social strategies with aspects of empowerment, capacity building and knowledge across sectors. The nature of the programmes means that some effects are likely to occur outside the healthcare sector; this breadth impacts on the choice of health and non-health outcomes to measure and value in an economic evaluation. Employing conventional outcome measures in evaluations of public health has been questioned. There are concerns that such measures are too narrow, overlook important dimensions of programme effect and, thus, lead to such interventions being undervalued. This issue is of particular importance for low-income and middle-income countries, which face considerable budget constraints, yet deliver a large proportion of health activities within public health programmes. The need to develop outcome measures, which include broader measures of quality of life, has given impetus to the development of a variety of new, holistic approaches, including Sen's capability framework and measures of subjective wellbeing. Despite their promise, these approaches have not yet been widely applied, perhaps because they present significant methodological challenges. This paper outlines the methodological challenges for the identification and measurement of broader outcomes of public health interventions in economic evaluation in low-income and middle-income countries. PMID- 26804361 TI - Using Economic Evidence to Set Healthcare Priorities in Low-Income and Lower Middle-Income Countries: A Systematic Review of Methodological Frameworks. AB - Policy makers in low-income and lower-middle-income countries (LMICs) are increasingly looking to develop 'evidence-based' frameworks for identifying priority health interventions. This paper synthesises and appraises the literature on methodological frameworks--which incorporate economic evaluation evidence--for the purpose of setting healthcare priorities in LMICs. A systematic search of Embase, MEDLINE, Econlit and PubMed identified 3968 articles with a further 21 articles identified through manual searching. A total of 36 papers were eligible for inclusion. These covered a wide range of health interventions with only two studies including health systems strengthening interventions related to financing, governance and human resources. A little under half of the studies (39%) included multiple criteria for priority setting, most commonly equity, feasibility and disease severity. Most studies (91%) specified a measure of 'efficiency' defined as cost per disability-adjusted life year averted. Ranking of health interventions using multi-criteria decision analysis and generalised cost-effectiveness were the most common frameworks for identifying priority health interventions. Approximately a third of studies discussed the affordability of priority interventions. Only one study identified priority areas for the release or redeployment of resources. The paper concludes by highlighting the need for local capacity to conduct evaluations (including economic analysis) and empowerment of local decision-makers to act on this evidence. PMID- 26804362 TI - Simultaneous face and voice processing in schizophrenia. AB - While several studies have consistently demonstrated abnormalities in the unisensory processing of face and voice in schizophrenia (SZ), the extent of abnormalities in the simultaneous processing of both types of information remains unclear. To address this issue, we used event-related potentials (ERP) methodology to probe the multisensory integration of face and non-semantic sounds in schizophrenia. EEG was recorded from 18 schizophrenia patients and 19 healthy control (HC) subjects in three conditions: neutral faces (visual condition-VIS); neutral non-semantic sounds (auditory condition-AUD); neutral faces presented simultaneously with neutral non-semantic sounds (audiovisual condition-AUDVIS). When compared with HC, the schizophrenia group showed less negative N170 to both face and face-voice stimuli; later P270 peak latency in the multimodal condition of face-voice relative to unimodal condition of face (the reverse was true in HC); reduced P400 amplitude and earlier P400 peak latency in the face but not in the voice-face condition. Thus, the analysis of ERP components suggests that deficits in the encoding of facial information extend to multimodal face-voice stimuli and that delays exist in feature extraction from multimodal face-voice stimuli in schizophrenia. In contrast, categorization processes seem to benefit from the presentation of simultaneous face-voice information. Timepoint by timepoint tests of multimodal integration did not suggest impairment in the initial stages of processing in schizophrenia. PMID- 26804363 TI - Introduction. PMID- 26804364 TI - A systematic review and meta-analysis of glycemic control for the prevention of diabetic foot syndrome. AB - OBJECTIVE: The objective of this review was to synthesize the available randomized controlled trials (RCTs) estimating the relative efficacy and safety of intensive vs less intensive glycemic control in preventing diabetic foot syndrome. METHODS: We used the umbrella design (systematic review of systematic reviews) to identify eligible RCTs. Two reviewers determined RCT eligibility and extracted descriptive, methodologic, and diabetic foot outcome data. Random effects meta-analysis was used to pool outcome data across studies, and the I(2) statistic was used to quantify heterogeneity. RESULTS: Nine RCTs enrolling 10,897 patients with type 2 diabetes were included and deemed to be at moderate risk of bias. Compared with less intensive glycemic control, intensive control (hemoglobin A1c, 6%-7.5%) was associated with a significant decrease in risk of amputation (relative risk [RR], 0.65; 95% confidence interval [CI], 0.45-0.94; I(2) = 0%). Intensive control was significantly associated with slower decline in sensory vibration threshold (mean difference, -8.27; 95% CI, -9.75 to -6.79). There was no effect on other neuropathic changes (RR, 0.89; 95% CI, 0.75-1.05; I(2) = 32%) or ischemic changes (RR, 0.92; 95% CI, 0.67-1.26; I(2) = 0%). The quality of evidence is likely moderate. CONCLUSIONS: Compared with less intensive glycemic control therapy, intensive control may decrease the risk of amputation in patients with diabetic foot syndrome. The reported risk reduction is likely overestimated because the trials were open and the decision to proceed with amputation could be influenced by glycemic control. PMID- 26804365 TI - A systematic review and meta-analysis of tests to predict wound healing in diabetic foot. AB - BACKGROUND: This systematic review summarized the evidence on noninvasive screening tests for the prediction of wound healing and the risk of amputation in diabetic foot ulcers. METHODS: We searched MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Scopus from database inception to October 2011. We pooled sensitivity, specificity, and diagnostic odds ratio (DOR) and compared test performance. RESULTS: Thirty-seven studies met the inclusion criteria. Eight tests were used to predict wound healing in this setting, including ankle-brachial index (ABI), ankle peak systolic velocity, transcutaneous oxygen measurement (TcPo2), toe-brachial index, toe systolic blood pressure, microvascular oxygen saturation, skin perfusion pressure, and hyperspectral imaging. For the TcPo2 test, the pooled DOR was 15.81 (95% confidence interval [CI], 3.36-74.45) for wound healing and 4.14 (95% CI, 2.98 5.76) for the risk of amputation. ABI was also predictive but to a lesser degree of the risk of amputations (DOR, 2.89; 95% CI, 1.65-5.05) but not of wound healing (DOR, 1.02; 95% CI, 0.40-2.64). It was not feasible to perform meta analysis comparing the remaining tests. The overall quality of evidence was limited by the risk of bias and imprecision (wide CIs due to small sample size). CONCLUSIONS: Several tests may predict wound healing in the setting of diabetic foot ulcer; however, most of the available evidence evaluates only TcPo2 and ABI. The overall quality of the evidence is low, and further research is needed to provide higher quality comparative effectiveness evidence. PMID- 26804366 TI - A systematic review and meta-analysis of debridement methods for chronic diabetic foot ulcers. AB - BACKGROUND: Several methods of debridement of diabetic foot ulcers are currently used. The relative efficacy of these methods is not well established. METHODS: This systematic review and meta-analysis was conducted to find the best available evidence for the effect of debridement on diabetic foot wound outcomes. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus through October 2011 for randomized controlled studies (RCTs) and observational comparative studies. RESULTS: We identified 11 RCTs and three nonrandomized studies reporting on 800 patients. The risk of bias was moderate overall. Meta-analysis of three RCTs showed that autolytic debridement significantly increased the healing rate (relative risk [RR], 1.89; 95% confidence interval [CI] 1.35-2.64). Meta-analysis of four studies (one RCT) showed that larval debridement reduced amputation (RR, 0.43; 95% CI, 0.21-0.88) but did not increase complete healing (RR, 1.27; 95% CI, 0.84-1.91). Surgical debridement was associated with shorter healing time compared with conventional wound care (one RCT). Insufficient evidence was found for comparisons between autolytic and larval debridement (one RCT), between ultrasound-guided and surgical debridement, and between hydrosurgical and surgical debridement. CONCLUSIONS: The available literature supports the efficacy of several debridement methods, including surgical, autolytic, and larval debridement. Comparative effectiveness evidence between these methods and supportive evidence for other methods is of low quality due to methodologic limitations and imprecision. Hence, the choice of debridement method at the present time should be based on the available expertise, patient preferences, the clinical context and cost. PMID- 26804367 TI - The management of diabetic foot: A clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine. AB - BACKGROUND: Diabetes mellitus continues to grow in global prevalence and to consume an increasing amount of health care resources. One of the key areas of morbidity associated with diabetes is the diabetic foot. To improve the care of patients with diabetic foot and to provide an evidence-based multidisciplinary management approach, the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine developed this clinical practice guideline. METHODS: The committee made specific practice recommendations using the Grades of Recommendation Assessment, Development, and Evaluation system. This was based on five systematic reviews of the literature. Specific areas of focus included (1) prevention of diabetic foot ulceration, (2) off-loading, (3) diagnosis of osteomyelitis, (4) wound care, and (5) peripheral arterial disease. RESULTS: Although we identified only limited high-quality evidence for many of the critical questions, we used the best available evidence and considered the patients' values and preferences and the clinical context to develop these guidelines. We include preventive recommendations such as those for adequate glycemic control, periodic foot inspection, and patient and family education. We recommend using custom therapeutic footwear in high-risk diabetic patients, including those with significant neuropathy, foot deformities, or previous amputation. In patients with plantar diabetic foot ulcer (DFU), we recommend off-loading with a total contact cast or irremovable fixed ankle walking boot. In patients with a new DFU, we recommend probe to bone test and plain films to be followed by magnetic resonance imaging if a soft tissue abscess or osteomyelitis is suspected. We provide recommendations on comprehensive wound care and various debridement methods. For DFUs that fail to improve (>50% wound area reduction) after a minimum of 4 weeks of standard wound therapy, we recommend adjunctive wound therapy options. In patients with DFU who have peripheral arterial disease, we recommend revascularization by either surgical bypass or endovascular therapy. CONCLUSIONS: Whereas these guidelines have addressed five key areas in the care of DFUs, they do not cover all the aspects of this complex condition. Going forward as future evidence accumulates, we plan to update our recommendations accordingly. PMID- 26804368 TI - A systematic review and meta-analysis of adjunctive therapies in diabetic foot ulcers. AB - BACKGROUND: Multiple adjunctive therapies have been proposed to accelerate wound healing in patients with diabetes and foot ulcers. The aim of this systematic review is to summarize the best available evidence supporting the use of hyperbaric oxygen therapy (HBOT), arterial pump devices, and pharmacologic agents (pentoxifylline, cilostazol, and iloprost) in this setting. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus through October 2011. Pairs of independent reviewers selected studies and extracted data. Predefined outcomes of interest were complete wound healing and amputation. RESULTS: We identified 18 interventional studies; of which 9 were randomized, enrolling 1526 patients. The risk of bias in the included studies was moderate. In multiple randomized trials, the addition of HBOT to conventional therapy (wound care and offloading) was associated with increased healing rate (Peto odds ratio, 14.25; 95% confidence interval, 7.08-28.68) and reduced major amputation rate (odds ratio, 0.30; 95% confidence interval, 0.10-0.89), compared with conventional therapy alone. In one small trial, arterial pump devices had a favorable effect on complete healing compared with HBOT and in another small trial compared with placebo devices. Neither iloprost nor pentoxifylline had a significant effect on amputation rate compared with conventional therapy. No comparative studies were identified for cilostazol in diabetic foot ulcers. CONCLUSIONS: There is low- to moderate-quality evidence supporting the use of HBOT as an adjunctive therapy to enhance diabetic foot ulcer healing and potentially prevent amputation. However, there are only sparse data regarding the efficacy of arterial pump devices and pharmacologic interventions. PMID- 26804369 TI - A systematic review and meta-analysis of off-loading methods for diabetic foot ulcers. AB - BACKGROUND: Increased plantar foot pressure is one of several key factors that lead to diabetic foot ulcers. Multiple methods have been proposed to relieve this pressure and thus enhance wound healing and potentially prevent relapse. We aimed in this systematic review to find the best available evidence for off-loading methods. METHODS: We searched MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and Scopus through October 2011. Pairs of independent reviewers selected studies and extracted data. Predefined outcomes of interest included complete wound healing, time to complete wound healing, amputation, infection, and relapse rates. RESULTS: We identified 19 interventional studies, of which 13 were randomized controlled trials, including data from 1605 patients with diabetic foot ulcers using an off-loading method. The risk of bias in the included studies was moderate. This analysis demonstrated improved wound healing with total contact casting over removable cast walker, therapeutic shoes, and conventional therapy. There was no advantage of irremovable cast walkers over total contact casting. There was improved healing with half-shoe compared with conventional wound care. Therapeutic shoes and insoles reduced relapse rate in comparison with regular footwear. Data were sparse regarding other off-loading methods. CONCLUSIONS: Although based on low-quality evidence (ie, evidence warranting lower certainty), benefits are demonstrated for use of total contact casting and irremovable cast walkers in the treatment of diabetic foot ulcers. Reduced relapse rate is demonstrated with various therapeutic shoes and insoles in comparison with regular footwear. PMID- 26804371 TI - Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations and breast cancer risk. AB - The World Cancer Research Fund/American Association for Cancer Research (WCRF/AICR) has published eight nutrition-related recommendations for the prevention of cancer. However, few prospective studies have examined these recommendations by breast cancer hormone receptor subtype and only one case control study has included the dietary supplements recommendation in their evaluation. We investigated whether adherence to the WCRF/AICR cancer prevention recommendations was associated with breast cancer incidence, overall and by hormone receptor subtype, in the Swedish Mammography Cohort. Among 31,514 primarily postmenopausal women diet and lifestyle factors were assessed with a self-administered food frequency questionnaire. A score was constructed based on adherence to the recommendations for body fatness, physical activity, energy density, plant foods, animal foods, alcoholic drinks and dietary supplements (score range 0-7). Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During 15 years of follow-up 1,388 cases of breast cancer were identified. Women who met six to seven recommendations had a 51% decreased risk of breast cancer compared to women meeting only zero to two recommendations (95% CI = 0.35-0.70). The association between each additional recommendation met and breast cancer risk was strongest for the ER-positive/PR-positive subtype (HR = 0.86; 95% CI = 0.79-0.94), while for the ER-negative/PR-negative subtype the individual recommendations regarding plant and animal foods were most strongly associated with reduced risk. Our findings support that adherence to the WCRF/AICR recommendations reduces breast cancer risk in a population of primarily postmenopausal women. Promoting these recommendations to the public could help reduce breast cancer incidence. PMID- 26804373 TI - Cycloartane and oleanane-type glycosides from Astragalus pennatulus. AB - Four new cycloartane and one new oleanane-type glycosides were isolated from Astragalus pennatulus along with five known cycloartane-type glycosides. The structures of the new compounds were established as 3-O-beta-D-xylopyranosyl-6-O beta-D-glucopyranosyl-3beta,6alpha,16beta-trihydroxy-24-oxo-20(R),25 epoxycycloartane (1), 3-O-[beta-D-glucuronopyranosyl-(1 -> 2)-beta-D xylopyranosyl]-3beta,16beta,24alpha-trihydroxy-20(R),25-epoxycycloartane (2), 3-O [beta-D-glucuronopyranosyl-(1 -> 2)-beta-D-xylopyranosyl]-3beta,16beta,25 trihydroxy-20(R),24(S)-epoxycycloartane (3), 3,25-di-O-beta-D-glucopyranosyl-6-O beta-D-xylopyranosyl-3beta,6alpha,16beta,25-tetrahydroxy-20(R),24(S) epoxycycloartane (4), 29-O-alpha-L-rhamnopyranosyl-abrisapogenol B (5) by 1D and 2D-NMR experiments along with ESIMS and HRMS analyses. The aglycone of compound 1, 3beta,6alpha,16beta-trihydroxy-24-oxo-20(R),25-epoxycycloartane, is reported for the first time. The cytotoxic activity of the isolated compounds was evaluated against three cancer cell lines including A549 (human lung adenocarcinoma), A375 (human melanoma) and DeFew (human B lymphoma) cells. None of the tested compounds caused a significant reduction of the cell number. PMID- 26804374 TI - Association of G/T(rs222859) polymorphism in Exon 1 of YBX2 gene with azoospermia, among Iranian infertile males. AB - Animal model studies have shown that MSY2 gene has a potential role in spermatogenesis. Some mutations on this gene have been proposed to be associated with human male infertility. In this study, polymorphisms of exon 1 of YBX2 gene have been investigated. A total of 276 men were evaluated. They included 96 men with normal spermatogenesis, 60 men with nonobstructive azoospermia, 60 men with oligospermia and 60 men with asthenospermia. We extracted DNA from blood and testis tissues of samples, and analysed polymorphisms of exon 1 by sequencing method. Moreover, YBX2 gene expression was studied by real-time PCR on blood and testis tissue of samples. Sequencing results showed that among the studied polymorphisms, frequency of TT genotype in rs222859 polymorphism was significantly higher in azoospermic patients compared to control group (P < 0.001). Azoospermic men exhibited significant underexpression of YBX2 gene in blood and testis samples in comparison with controls, oligosperm and asthenosperm samples (P < 0.001), but there was no significant difference in gene expression of YBX2 gene in blood and testis tissues of azoospermic men, with and without mutation (P > 0.05). According to our results, the alterations of this gene might be involved in azoospermia among Iranian population. PMID- 26804375 TI - Synthesis of Novel Oxazolo[4,5-b]pyridine-2-one based 1,2,3-triazoles as Glycogen Synthase Kinase-3beta Inhibitors with Anti-inflammatory Potential. AB - A novel series of oxazolo[4,5-b]pyridine-2-one based 1,2,3-triazoles has been synthesized by click chemistry approach and evaluated for in vitro GSK-3beta inhibitory activity. Compound 4g showed maximum inhibition with IC50 value of 0.19 MUm. Keeping in view the effect of GSK-3beta inhibition on inflammation, compounds 4g, 4d, 4f, 4i, 4n and 4q exhibiting significant GSK-3beta inhibition were examined for in vivo anti-inflammatory activity in rat paw edema model. The compounds 4g, 4d, 4f and 4i showed pronounced in vivo anti-inflammatory activity (76.36, 74.54, 72.72 and 70.90%, respectively, after 5h post-carrageenan administration) and were further found to inhibit the pro-inflammatory mediators, viz. NO, TNF-alpha, IL-1beta, and IL-6 substantially in comparison with indomethacin, an anti-inflammatory drug as well as SB216763, a GSK-3beta inhibitor, reported to exert a similar effect. Histopathology studies confirmed the tolerance of gastric mucosa to these compounds. PMID- 26804376 TI - Erythromelalgia-like presentation of chronic acquired demyelinating polyneuropathy in a setting of past alcohol abuse. AB - Erythromelalgia may be primary or secondary to an underlying medical condition. Association with small fiber neuropathy and axonal large fiber peripheral neuropathy has been described. Erythromelalgia in the setting of acquired demyelinating neuropathy has not been reported. We report a 52-year-old woman with severe erythromelalgia, pain and burning, progressive weakness, hyporeflexia and distal pan-sensory deficits. Cerebrospinal fluid protein was 219 mg/dL. Nerve conduction study revealed extreme (ten-fold) prolongation of distal motor latencies, markedly slow motor nerve conduction, reduced terminal latency index, reduced distal compound muscle action potential (CMAP) amplitude, possible conduction blocks, and distal denervation. Treatment with intravenous immunoglobulin, prednisone and azathioprine resulted in marked clinical and electrophysiological improvement. Our patient fulfills the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP); however, the unique electrodiagnostic features and presentation with erythromelalgia may represent a CIDP variant or a novel dysimmune neuropathy, or may partly be related to neurotoxic effects of prior alcohol abuse. PMID- 26804378 TI - Evaluation of eye, head and trunk coordination during target tracking tasks. AB - This study tested the feasibility of a method to synchronise and to evaluate eye, head and trunk movement patterns during target tracking tasks performed by 10 subjects. A projected central target was randomly repositioned at 40 degrees and 70 degrees of rotation to the left and right. Subjects were instructed to change gaze as quickly as possible. Head and trunk motion was measured using a motion analysis system, and eye movement was measured using an eye-tracker; all data were synchronised. For healthy subjects, the eye moved faster than the head, there was no trunk movement and the head moved more than the eye to reach further displaced targets. The method tested was feasible, and it could be used to evaluate eye, head and trunk movement patterns of subjects with injuries such as whiplash and concussions. Practitioner Summary: Studies of eye, head and trunk movements using synchronised methods are needed. We tested the feasibility of a method to synchronise and evaluate eye, head and trunk movement patterns. The method tested was feasible, and it could be used to evaluate movement patterns of subjects with injuries such as whiplash. PMID- 26804377 TI - The architecture of the Schizosaccharomyces pombe CCR4-NOT complex. AB - CCR4-NOT is a large protein complex present both in cytoplasm and the nucleus of eukaryotic cells. Although it is involved in a variety of distinct processes related to expression of genetic information such as poly(A) tail shortening, transcription regulation, nuclear export and protein degradation, there is only fragmentary information available on some of its nine subunits. Here we show a comprehensive structural characterization of the native CCR4-NOT complex from Schizosaccharomyces pombe. Our cryo-EM 3D reconstruction of the complex, combined with techniques such as immunomicroscopy, RNA-nanogold labelling, docking of the available high-resolution structures and models of different subunits and domains, allow us to propose its full molecular architecture. We locate all functionally defined domains endowed with deadenylating and ubiquitinating activities, the nucleus-specific RNA-interacting subunit Mmi1, as well as surfaces responsible for protein-protein interactions. This information provides insight into cooperation of the different CCR4-NOT complex functions. PMID- 26804379 TI - Ethics and professional responsibility: Essential dimensions of planned home birth. AB - Planned home birth is a paradigmatic case study of the importance of ethics and professionalism in contemporary perinatology. In this article we provide a summary of recent analyses of the Centers for Disease Control database on attendants and birth outcomes in the United States. This summary documents the increased risks of neonatal mortality and morbidity of planned home birth as well as bias in Apgar scoring. We then describe the professional responsibility model of obstetric ethics, which is based on the professional medical ethics of two major figures in the history of medical ethics, Drs. John Gregory of Scotland and Thomas Percival of England. This model emphasizes the identification and careful balancing of the perinatologist's ethical obligations to pregnant, fetal, and neonatal patients. This model stands in sharp contrast to one-dimensional maternal-rights-based reductionist model of obstetric ethics, which is based solely on the pregnant woman's rights. We then identify the implications of the professional responsibility model for the perinatologist's role in directive counseling of women who express an interest in or ask about planned home birth. Perinatologists should explain the evidence of the increased, preventable perinatal risks of planned home birth, recommend against it, and recommend planned hospital birth. Perinatologists have the professional responsibility to create and sustain a strong culture of safety committed to a home-birth-like experience in the hospital. By routinely fulfilling these professional responsibilities perinatologists can help to prevent the documented, increased risks planned home birth. PMID- 26804380 TI - The safe motherhood initiative: The development and implementation of standardized obstetric care bundles in New York. AB - The medical literature demonstrates that inadequate hospital protocols or the lack of consistent protocols for diagnosis, management, consultation, and/or referral can lead to confusion and unnecessary variation in patient care. Incongruities in clinical settings have been repeatedly shown to compromise quality of patient outcomes. Accordingly, the development and adoption of standardized protocols as the best practice for addressing incidence of adverse events remains a top priority in health care quality and safety initiatives. Among the 127 hospital facilities that provide inpatient obstetrical care in New York State, adoption and uptake of standardized care management plans is sporadic at best. In 2001, to target the incidence of severe maternal outcomes and enhance the state of maternal health in New York, the American Congress of Obstetricians and Gynecologists (ACOG) District II and the New York State Department of Health developed the Safe Motherhood Initiative. Today, the Initiative demonstrates that maternal care outcomes are well served through an organized culture of obstetric safety. ACOG District II assists hospitals to optimize their delivery of obstetric care via three toolkits containing standardized protocols for the diagnosis, prevention, and management of the leading causes of maternal mortality and morbidity: hemorrhage, hypertension, and pulmonary embolus. PMID- 26804381 TI - Ethical issues in neonatal research involving human subjects. AB - Research involving critically ill neonates creates many ethical challenges. Neonatal clinical research has always been hard to perform, is very expensive, and may generate some unique ethical concerns. This article describes some examples of historical and modern controversies in neonatal research, discusses the justification for research involving such vulnerable and fragile patients, clarifies current federal regulations that govern research involving neonates, and suggests ways that clinical investigators can develop and implement ethically grounded human subjects research. PMID- 26804382 TI - Reliability and measurement precision of concentric-to-isometric and eccentric-to isometric knee active joint position sense tests in uninjured physically active adults. AB - OBJECTIVES: Proprioception is important because it is used by the central nervous system to mediate muscle control of joint stability, posture, and movement. Knee active joint position sense (AJPS) is one representation of knee proprioception. The purpose of this study was to establish the intra-tester, inter-session, test retest reliability of concentric-to-isometric (seated knee extension; prone knee flexion) and eccentric-to-isometric (seated knee flexion; prone knee extension) knee AJPS tests in uninjured adults. DESIGN: Descriptive. SETTING: University laboratory. PARTICIPANTS: Six males, six females (age 26.2 +/- 5.7 years; height 171.1 +/- 9.6 cm; mass 71.1 +/- 16.6 kg). MAIN OUTCOME MEASURES: Mean absolute error (AE; degrees ); intraclass correlation coefficient (ICC) (2,1); standard error of measurement (SEM; degrees ). RESULTS: Mean AE ranged from 3.18 degrees to 5.97 degrees across tests. The ICCs and SEMs were: seated knee extension 0.13, 1.3 degrees ; prone knee flexion 0.51, 1.2 degrees ; seated knee flexion 0.31, 1.7 degrees ; prone knee extension 0.87, 1.4 degrees . CONCLUSIONS: The prone knee flexion and prone knee extension tests demonstrated moderate to good reliability. Prone knee flexion and prone knee extension AJPS tests may be useful in cross-sectional studies estimating how proprioception contributes to knee functional joint stability or prospective studies estimating the role of proprioception in the onset of knee injury. PMID- 26804383 TI - No Cancer Without a Colon? Think Again! Colorectal Cancer Risk After Colectomy for Inflammatory Bowel Diseases. PMID- 26804384 TI - Targeted Biopsies Identify Larger Proportions of Patients With Colonic Neoplasia Undergoing High-Definition Colonoscopy, Dye Chromoendoscopy, or Electronic Virtual Chromoendoscopy. AB - BACKGROUND & AIMS: It is unclear what are the best and most appropriate endoscopic procedures for detecting colonic neoplasia in patients with long-term colonic inflammatory bowel disease (IBD). Dye chromoendoscopy (DCE) is the standard used in IBD surveillance colonoscopies. However, studies are needed to determine the optimal endoscopic technique for detecting dysplastic lesions. We investigated current practices used in surveillance colonoscopies by IBD gastroenterologists at a single tertiary center. We also determined the rate of neoplasia detection among different surveillance endoscopic techniques in an analysis of random or targeted biopsies. METHODS: We collected data on 454 patients with IBD (54.5% male; mean age, 50 y; mean disease duration, 14.5 y; 55.9% with ulcerative colitis, 42.7% with Crohn's disease, and 1.3% with indeterminate colitis) who underwent surveillance colonoscopy from April 2011 through March 2014 at the University of Calgary in Canada. Subjects were examined using white-light standard-definition endoscopy (WLE), high-definition (HD) colonoscopy, virtual electronic chromoendoscopy (VCE), or DCE; random or targeted biopsy specimens were collected. Endoscopic and histologic descriptions with suspected neoplasia were recorded. Rates of neoplasia detection by the different endoscopic procedures were compared using chi-square analysis. RESULTS: Of the patients analyzed, 27.7% had WLE endoscopy with random collection of biopsy specimens, 27.3% had HD colonoscopy with random collection of biopsy specimens, 14.1% had VCE with random collection of biopsy specimens, 0.9% had DCE with random collection of biopsy specimens, 12.8% had HD colonoscopy with collection of targeted biopsy specimens, 11.9% had VCE with collection of targeted biopsy specimens, and 5.3% had DCE with collection of targeted biopsy specimens. Neoplastic lesions were detected in 8.2% of the procedures performed in the random biopsy group (95% confidence interval, 5.6-11.7) and 19.1% of procedures in the targeted biopsy group (95% confidence interval, 13.4-26.5) (P < .001). Neoplasias were detected in similar proportions of patients by HD colonoscopy, VCE, or DCE, with targeted biopsy collection. CONCLUSIONS: In a large cohort of IBD patients undergoing surveillance colonoscopy, targeted biopsies identified greater proportions of subjects with neoplasia than random biopsies. Targeted collection of biopsy specimens appears to be sufficient for detecting colonic neoplasia in patients undergoing HD colonoscopy, DCE, or VCE, but not WLE. PMID- 26804386 TI - Colonoscopy Identifies Increased Prevalence of Large Polyps or Tumors in Patients 40-49 Years Old With Hematochezia vs Other Gastrointestinal Indications. AB - BACKGROUND & AIMS: There is an unclear role for colonoscopy in the evaluation of symptomatic individuals younger than 50 years old. We aimed to determine the prevalence of large polyps (>9 mm) or tumors in individuals 40 to 49 years old who underwent colonoscopy for various signs and symptoms, and compare the results with those from average-risk individuals ages 50 to 54 years who underwent screening colonoscopy. METHODS: We collected data from a national endoscopy database, from 2000 through 2012, and identified patients 40 to 49 years old who underwent colonoscopy for bleeding and nonbleeding indications. The prevalence of large polyps (>9 mm) or tumors was compared with the prevalence in a reference group (n = 99,713 average-risk individuals ages 50-54 undergoing screening colonoscopy). RESULTS: A total of 65,892 patients ages 40 to 49 years underwent colonoscopy for a variety of indications. Significantly larger proportions of male and female patients with hematochezia without anemia or iron-deficiency anemia (IDA) had large polyps or tumors (7.2%) compared with the reference group (men, 7.2% vs 6.2%; P = .0001; and women, 5.5% vs 4.1%; P < .0001). Patients with weight loss, anemia or IDA, or hematochezia with anemia or IDA did not have a significantly higher prevalence of large polyps or tumors than the reference group. Significantly lower proportions of patients with general gastrointestinal symptoms (pain, bloating, or change in bowel habits) had advanced neoplasia compared with the reference group (men, 3.9% vs 6.2%; P < .0001; and women, 2.7% vs 4.1%; P < .0001). CONCLUSIONS: An analysis of a national endoscopy database supports the role of colonoscopy to evaluate hematochezia in patients 40 to 49 years old. A lower proportion of patients with anemia, weight loss, and general abdominal symptoms had large polyps or tumors compared with average-risk patients 50 to 54 years old. A significantly lower proportion of patients younger than 50 years with general gastrointestinal symptoms had large polyps-these patients are therefore less likely to benefit from colonoscopy. PMID- 26804385 TI - Serum Biomarkers Indicate Long-term Reduction in Liver Fibrosis in Patients With Sustained Virological Response to Treatment for HCV Infection. AB - BACKGROUND & AIMS: Sustained virological response (SVR) to antiviral therapy for hepatitis C virus (HCV) correlates with changes in biochemical measures of liver function. However, little is known about the long-term effects of SVR on liver fibrosis. We investigated the effects of HCV therapy on fibrosis, based on the Fibrosis-4 (FIB4) score, over a 10-year period. METHODS: We collected data from participants in the Chronic Hepatitis Cohort Study-a large observational multicenter study of patients with hepatitis at 4 US health systems-from January 1, 2006, through December 31, 2013. We calculated patients' FIB4 score and the aminotransferase-to-platelet ratio index (APRI) score over a 10-year period. Of 4731 patients with HCV infection, 1657 (35%) were treated and 755 (46%) of these patients achieved SVR. RESULTS: In propensity score-adjusted analyses, we observed significant longitudinal changes in FIB4 score that varied with treatment and response to treatment. In patients achieving SVR, FIB4 scores decreased sharply, remaining significantly lower over the 10-year period than in untreated patients or patients with treatment failure (P < .001). In independent analyses, men and patients with HCV genotype 1 or 3 infections had higher FIB4 scores than women or patients with HCV genotype 2 infections (P < .01 for both). Findings were similar in a sensitivity analysis that substituted the APRI as the marker of fibrosis instead of the FIB4 score. CONCLUSIONS: SVR to HCV treatment appears to induce long-term regression of fibrosis based on FIB4 scores collected over 10 years from a large observational study of US hepatitis patients. Patients receiving no treatment or with treatment failure had progressive increases in FIB4 scores. PMID- 26804387 TI - Myocardial fibrosis seen through the lenses of T-cell biology. AB - Lymphocytes came recently into focus as modulators of non-infectious myocardial diseases. Several lines of experimental evidence now indicate that CD4(+) T-cells can influence the healing and scarring processes that follow a myocardial infarction episode. Furthermore, such heart-directed T-cell activity has also been implicated in the pathogenesis cardiac remodeling that develops in response to chronic pressure-overload conditions. Mechanistically, different T-cell subsets can secrete several mediators and growth factors that influence the myocardial molecular milieu and directly interfere with the macrophages' and fibroblasts' activity. Therefore, the present review summarizes the current experimental evidence on the role of T-cells in myocardial scar formation after infarction and myocardial fibrosis as central mechanism of ventricular remodeling. PMID- 26804423 TI - Near-IR Emitting Iridium(III) Complexes with Heteroaromatic beta-Diketonate Ancillary Ligands for Efficient Solution-Processed OLEDs: Structure-Property Correlations. AB - Three NIR-emitting neutral Ir(III) complexes [Ir(iqbt)2 (dpm)] (1), [Ir(iqbt)2 (tta)] (2), and [Ir(iqbt)2 (dtdk)] (3) based on the 1-(benzo[b]thiophen-2-yl) isoquinolinate (iqtb) were synthesized and characterized (dpm=2,2,6,6-tetramethyl 3,5-heptanedionate; tta=2-thienoyltrifluoroacetonate; dtdk=1,3-di(thiophen-2 yl)propane-1,3-dionate). The compounds emit between lambda=680 and 850 nm with high luminescence quantum yields (up to 16 %). By combining electrochemistry, photophysical measurements, and computational modelling, the relationship between the structure, energy levels, and properties were investigated. NIR-emitting, solution-processed phosphorescent organic light-emitting devices (PHOLEDs) were fabricated using the complexes. The devices show remarkable external quantum efficiencies (above 3 % with 1) with negligible efficiency roll-off values, exceeding the highest reported values for solution-processible NIR emitters. PMID- 26804426 TI - Current approaches to the management of patients with liver cirrhosis who have acute esophageal variceal bleeding. AB - OBJECTIVE: Esophageal variceal bleeding is the most dangerous complication in patients with liver cirrhosis, and it is accompanied by high mortality. Their treatment can be complex, and requires a multidisciplinary approach. This review examines current approaches to the management of patients with liver cirrhosis who have acute esophageal variceal bleeding. METHODS: PubMed, Google Scholar, and Cochrane Systematic Reviews were searched for articles published between 1987 and 2015. Relevant articles were identified using the following terms: 'esophageal variceal bleeding', 'portal hypertension' and 'complications of liver cirrhosis'. The reference lists of articles identified were also searched for other relevant publications. Inclusion criteria were restricted to the management of patients with liver cirrhosis who have acute esophageal variceal bleeding. RESULTS: It is currently recommended to combine vasoactive drugs (preferable somatostatin or terlipressin) and endoscopic therapies (endoscopic band ligation as first choice, sclerotherapy if endoscopic band ligation not feasible) for the initial treatment of acute variceal bleeding. Antibiotic prophylaxis must be regarded as an integral part of the treatment. The use of a Sengstaken-Blakemore tube is appropriate only in cases of refractory bleeding if the above methods cannot be used. An alternative to balloon tamponade may be the installation of self expandable metal stents. The transjugular intrahepatic portosystemic shunt is an extremely useful technique for the treatment of acute bleeding from esophageal varices. Although most current clinical guidelines classify it as second-line therapy, the Baveno VI workshop recommends early transjugular intrahepatic portosystemic shunt with expanded polytetrafluoroethylene-covered stents within 72 h (ideally <24 h) in patients with esophageal variceal bleeding at high risk of treatment failure (e.g. Child-Turcotte-Pugh class C < 14 points or Child Turcotte-Pugh class B with active bleeding) after initial pharmacological and endoscopic therapy. Urgent surgical intervention is rarely performed and can be considered only in case of failure of conservative and/or endoscopic therapy and being unable to use a transjugular intrahepatic portosystemic shunt. Among surgical operations described in the literature are a variety of portocaval anastomosis and azygoportal disconnection procedures. CONCLUSIONS: To improve the results of treatment for patients with liver cirrhosis who develop acute esophageal variceal bleeding, it is important to stratify patients into risk groups, which will allow one to tailor therapeutic approaches to the expected results. PMID- 26804425 TI - Functional characterization and transcriptome analysis reveal multiple roles for prc in the pathogenicity of the black rot pathogen Xanthomonas campestris pv. campestris. AB - Gram-negative phytopathogenic Xanthomonas campestris pv. campestris (Xcc) is the causal agent of black rot in crucifers. The ability of Xcc to incite this disease in plants depends on a number of factors, including exopolysaccharides, extracellular enzymes and biofilm production. In this study, transposon mutagenesis led to identification of the prc gene, encoding a tail-specific protease, which plays a role in Xcc pathogenesis. Mutation of prc resulted in decreased virulence, extracellular protease production and bacterial attachment, with restoration to the levels of wild type by the intact prc gene. From subsequent quantitative RT-PCR analysis and reporter assay, the major extracellular protease gene prt1, biofilm-related gene galE encoding a UDP galactose 4-epimerase and two putative adhesin genes (yapH and XC_4290 encoding autotransporter-like protein H and hemagglutinin, respectively) were found to be reduced in the prc mutant. Results of transcriptome profiling of Xcc wild type and prc mutant by RNA sequencing (RNA-Seq) showed that mutation of prc in Xcc leads to alteration in the transcriptional levels (more than twofold) of 91 genes. These differentially expressed genes were associated with a wide range of biological functions such as carbohydrate transport and metabolism, cell wall/membrane biogenesis, posttranslational modification, protein turnover and chaperones, inorganic ion transport and metabolism and signal transduction mechanisms. The results of this study facilitate the functional understanding of and provide new information about the regulatory role of prc. PMID- 26804428 TI - Influence of prebiotics on Lactobacillus reuteri death kinetics under sub-optimal temperatures and pH. AB - Eaten foodstuffs are usually fortified with prebiotic ingredients, such as inulin and oligofructose (FOS). The main goal of this study was to evaluate the combined effects of inulin and FOS with either suboptimal pH or storage temperature on the viability of Lactobacillus reuteri DSM 20016. Data were modeled through Weibull equation for the evaluation of the microbiological shelf life and the survival time. Prebiotics enhanced the microbiological shelf life and enhanced the survival time of the target bacterium. The use of the factorial ANOVA highlighted that inulin and FOS exerted a different effect as a function of pH and temperature. Inulin prolonged survival time under acidic conditions, while the effect of glucose + FOS was significant at pH 8. Finally, temperature could act by increasing or decreasing the effect of prebiotics, as they could exert a protective effect at 30 degrees C but not at 44 degrees C. As the main output of this research, we could suggest that the effect of prebiotics on L. reuteri could be significantly affected by pH and temperature, thus pinpointing that the design of a symbiotic food should also rely on these factors. PMID- 26804424 TI - F-BOX proteins in cancer cachexia and muscle wasting: Emerging regulators and therapeutic opportunities. AB - Cancer cachexia is a debilitating metabolic syndrome accounting for fatigue, an impairment of normal activities, loss of muscle mass associated with body weight loss eventually leading to death in majority of patients with advanced disease. Cachexia patients undergoing skeletal muscle atrophy show consistent activation of the SCF ubiquitin ligase (F-BOX) family member Atrogin-1 (also known as MAFBx/FBXO32) alongside the activation of the muscle ring finger protein1 (MuRF1). Other lesser known F-BOX family members are also emerging as key players supporting muscle wasting pathways. Recent work highlights a spectrum of different cancer signaling mechanisms impacting F-BOX family members that feed forward muscle atrophy related genes during cachexia. These novel players provide unique opportunities to block cachexia induced skeletal muscle atrophy by therapeutically targeting the SCF protein ligases. Conversely, strategies that induce the production of proteins may be helpful to counter the effects of these F-BOX proteins. Through this review, we bring forward some novel targets that promote atrogin-1 signaling in cachexia and muscle wasting and highlight newer therapeutic opportunities that can help in the better management of patients with this devastating and fatal disorder. PMID- 26804430 TI - Radical Cystectomy-The Waiting is the Hardest Part...or is it? PMID- 26804431 TI - The Isolated Anterior Prolapse Repair: Its Evolution and Current Role. PMID- 26804432 TI - Editorial Comment. PMID- 26804433 TI - New Frontiers in Stone Disease: Immune Cells. PMID- 26804434 TI - [Cutaneous manifestations of sarcoidosis]. AB - Sarcoidosis is a systemic granulomatous disorder of unknown aetiology. Its dermatological manifestations are extremely polymorphous. They are normally classed as either specific lesions, comprising granulomas, which are generally chronic, or non-specific lesions, principally acute erythema nodosum. These signs are seen in around 25% of sarcoidosis patients. The disease may be heralded by a skin disorder. Diagnosis of cutaneous sarcoidosis provides the clinician with three problems: screening for a visceral site of the disease, determination of the prognosis, and long-term management with regular monitoring coupled with suitable therapy in the event of cosmetic or functional impairment. PMID- 26804436 TI - A Nonmetric Scaling Approach To Taxonomies Of Employee Work Motivation. AB - A nonmetric scaling method was used to test several taxonomies of work motivation. The intercorrelations among the importance ratings of 14 work goals, made by 800 salesmen and 1,800 repairmen were analyzed. A two-space solution was deemed adequate to reflect both the empirical and theoretical interrelationships among the variables. These results were consistent with an intrinsic-extrinsic grouping of the variables, but more complex relationships of motivational variables were also revealed. In particular, Alderfer's tripartite classification and Maslow's five-fold hierarchy were strongly supported by the smallest space analyses for both salesmen and repairmen. PMID- 26804435 TI - Association between pulmonary vein orientation and ablation outcome in patients undergoing multi-electrode ablation for atrial fibrillation. AB - BACKGROUND: Previous studies reported on the impact of pulmonary vein orientation on pulmonary vein isolation (PVI) outcome in atrial fibrillation patients undergoing laser balloon PVI and point-by-point radiofrequency ablation. OBJECTIVE: Demonstrate the association between pulmonary vein orientation and PVI outcome after multi-electrode radiofrequency ablation. METHODS: 120 patients undergoing PVI with a circular MER catheter were included. A left atrial ECG triggered CT was performed in all patients prior to PVI. The orientation of all pulmonary veins at the insertion into the left atrium was measured in the axial and coronal planes. pulmonary veins were classified as having a ventral/dorsal and caudal/cranial orientation depending on the pulmonary vein trunk angle as compared to the median angle. RESULTS: Mean age was 56 years, arrhythmia-free survival after a median follow-up of 20 months was 54.2%. Left upper pulmonary vein orientation within the coronal plane was associated with arrhythmia-free survival, ranging from 58% with a cranial pulmonary vein orientation to 21% with a caudal orientation (p = 0.003). Similarly, arrhythmia-free survival was 50% in patients with a caudal orientation and 33% in patients with a cranial orientation of the left lower pulmonary vein in the coronal plane (p = 0.036). Pulmonary vein orientation in the axial plane and orientation of the right-sided pulmonary veins were not associated with arrhythmia-free survival. Multivariable analysis showed an independent association between both left upper (hazard ratio 2.8, p = 0.001) and left lower (hazard ratio 0.490, p = 0.034) pulmonary vein orientation and arrhythmia-free survival. CONCLUSION: In MER ablation, orientation of the left upper and caudalpulmonary veins in the coronal plane were independently associated with arrhythmia-free survival after multi-electrode PVI. PMID- 26804437 TI - Very Simple Structure: An Alternative Procedure For Estimating The Optimal Number Of Interpretable Factors. AB - A new procedure for determining the optimal number of interpretable factors to extract from a correlation matrix is introduced and compared to more conventional procedures. The new method evaluates the magnitude of the Very Simple Structure index of goodness of fit for factor solutions of increasing rank. The number of factors which maximizes the VSS criterion is taken as being the optimal number of factors to extract. Thirty-two artificial and two real data sets are used in order to compare this procedure with such methods as maximum likelihood, the eigenvalue greater than 1.0 rule, and comparison of the observed eigenvalues with those expected from random data. PMID- 26804438 TI - A Multidimensional Scaling Analysis Of Sex Guilt. AB - Sixty males and sixty females, divided into groups of high and low sex-guilt, made all possible comparisons between fifteen descriptions of individuals. These descriptions were written to reflect characteristics felt to be important to the concept of sex guilt. Ratings of dissimilarity were analyzed by INDSCAL and an unfolding method, both of which are multidimensional scaling techniques. Results indicated that: 1) low sex guilt and high sex guilt subjects perceived the stimulus "individuals" quite similarly along the two major dimensions (sociability and positive-negative) underlying their comparisons; 2) that males and high sex guilt subjects utilized less of both the sociability and positive negative dimensions in making their judgments concerning the interrelationships of the stimulus "individuals"; 3) that low sex guilt and high sex guilt subjects differ in evaluating themselves in relation to the stimulus "individuals"; and 4) high sex guilt subjects rated themselves as more similar to a trait sex guilty description than to descriptions dealing with trait sex anxiety, or general guilt or anxiety. It was concluded that: 1) low sex guilt and high sex guilt subjects differ in the value they place on different personal attributes; and 2) D. L. Mosher's model of preservation of self-esteem best explained the behavior of high sex guilt individuals. PMID- 26804439 TI - Three-Mode Common Factor Analysis: Procedure And Computer Programs. AB - As psychologists increasingly recognize the limitations of single-occasion, single-measure research designs and employ more elaborate and comprehensive data collection schemes, sophisticated analytic techniques will play an ever more important role in understanding behavioral data. This paper outlines one such promising technique, Tucker's three-mode factor analysis, which enables the researcher to explore new taxonomic structures in three-way designs. The procedure is described in step-by-step format, which should be easy to follow for anyone familiar with traditional two-mode factor analysis. Appropriate computer programs are available to interface with the widely used SPSS package to calculate Tucker's common factor model. PMID- 26804440 TI - The Structure Of Self-Reported Difficulty In Assertiveness: An Application Of Three-Mode Common Factor Analysis. AB - The Difficulty in Assertiveness Inventory (DAI) was developed, based on a two facet model of assertiveness for item specification -- referents (interpersonal contexts or partners) x response classes (types of assertive behavior). Data from two samples of female university students were subjected to three-mode factor analysis. Two referent, two response class, and five individual differences factors were extracted. The proportion of variance accounted for by each factor matched across solutions. The patterns of factor loadings indicated that the two referent factors (distant and close), the two response class factors (positive and negative), and four of the five individual differences factors (labeled Assertiveness A, B, C, and D) were stable across subject samples. Solutions for the individual differences factor matrix and the counter-rotated and transformed core matrix were reciprocally beneficial to interpretation of the structure of the data. Correlations of DAI subscales with the Marlowe-Crowne Social Desirability Scale were not significantly different from zero. The potential uses of the instrument in applied research and in the clinical setting were discussed. PMID- 26804441 TI - Social Areas And The Wellbeing Of Tenants In Housing For The Elderly. AB - The relationships between objective neighborhood characteristics and the wellbeing of 2421 elderly federally-assisted housing tenants were investigated. Six factors were derived from the 1970 Census characteristics of the social areas in which 150 housing projects were located. Social-area factors accounted for significant proportions of variance in tenant activity participation, housing satisfaction, friendship behavior, and motility, but not family interaction or morale. Higher neighborhood age density was consistently associated with tenant wellbeing. Neither the racial character of the neighborhood or the consonance between race of tenant and the neighborhood racial context were associated with wellbeing, but consonance between tenant's race and the racial context of the housing was associated with wellbeing. PMID- 26804442 TI - On The Robustness Of Factor Analysis Against Crude Classification Of The Observations. AB - The paper is concerned with the consequences for maximum likelihood factor analysis which may follow if the observed variables are ordinal with only a few scale steps, which are assigned integer values. It is hypothesized that the observed variables are obtained through a classification of some true variables, which are multivariate normal and for which a factor model holds. Using simple formulas for the relations between true correlations and correlations based on the classified variables, we demonstrate numerically the relationships between true factor models and results obtained from classified data. This is done for several choices of thresholds, true factor loadings and numbers of variables, assuming a one-factor model. The results indicate that classification may lead to a substantial lack of fit of the model, i.e. an erroneous indication that more factors are needed. This is especially true if the variables are skewed in opposite direction and have high true loadings, but does not depend much on the number of scale steps. The classification also attenuates the loading estimates, and this effect is increased with a decreasing number of scale steps and increasing variation in skewness among the variables. PMID- 26804443 TI - Carnosic acid attenuates neuropathic pain in rat through the activation of spinal sirtuin1 and down-regulation of p66shc expression. AB - BACKGROUND: It has been reported that carnosic acid (CA) exhibits a range of biological activities including hepatoprotective, antioxidant and anti inflammatory. However, the effect of carnosic acid in neuropathic pain remained elusive. METHODS: A neuropathic pain model of chronic constriction injury (CCI) was established in adult male Sprague-Dawley rats. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were recorded, and western blot was performed to detect sirtuin1 and p66shc content. RESULTS: Intrathecal administration of carnosic acid attenuated mechanical allodynia and thermal hyperalgesia in rats following chronic constriction injury. Interestingly, carnosic acid analgesic effect was positively associated with spinal sirtuin1 activation; however, p66shc was inhibited by carnosic acid in the spinal cord. In additional, sirtuin1 inhibitor EX-527 reversed the anti-nociceptive effect of carnosic acid. CONCLUSIONS: Carnosic acid is effective in the treatment of the established CCI-induced pain. It may be possible that spinal sirtuin1 activition by carnosic acid attenuates neuropathic pain through a mechanism involving the down-regulation of p66shc expression. PMID- 26804444 TI - Creatine affords protection against glutamate-induced nitrosative and oxidative stress. AB - Creatine has been reported to exert beneficial effects in several neurodegenerative diseases in which glutamatergic excitotoxicity and oxidative stress play an etiological role. The purpose of this study was to investigate the protective effects of creatine, as compared to the N-Methyl-d-Aspartate (NMDA) receptor antagonist dizocilpine (MK-801), against glutamate or hydrogen peroxide (H2O2)-induced injury in human neuroblastoma SH-SY5Y cells. Exposure of cells to glutamate (60-80 mM) or H2O2 (200-300 MUM) for 24 h decreased cellular viability and increased dichlorofluorescein (DCF) fluorescence (indicative of increased reactive oxygen species, ROS) and nitric oxide (NO) production (assessed by mono nitrogen oxides, NOx, levels). Creatine (1-10 mM) or MK-801 (0.1-10 MUM) reduced glutamate- and H2O2-induced toxicity. The protective effect of creatine against glutamate-induced toxicity involves its antioxidant effect, since creatine, similar to MK-801, prevented the increase on DCF fluorescence induced by glutamate or H2O2. Furthermore, creatine or MK-801 blocked glutamate- and H2O2 induced increases in NOx levels. In another set of experiments, the repeated, but not acute, administration of creatine (300 mg/kg, po) in mice prevented the decreases on cellular viability and mitochondrial membrane potential (assessed by tetramethylrhodamine ethyl ester, TMRE, probe) of hippocampal slices incubated with glutamate (10 mM). Creatine concentration-dependent decreased the amount of nitrite formed in the reaction of oxygen with NO produced from sodium nitroprusside solution, suggesting that its protective effect against glutamate or H2O2-induced toxicity might be due to its scavenger activity. Overall, the results suggest that creatine may be useful as adjuvant therapy for neurodegenerative disease treatments. PMID- 26804445 TI - Investigation of the structural preference and flexibility of the loop residues in amyloid fibrils of the HET-s prion. AB - The structural variability of a 16-residue loop (residues 246-261) which is in part disordered and connects two layers of the beta-solenoid formed by the prion form of HET-s and its prion domain HET-s(218-289) is investigated using molecular dynamics computer simulation. A system of three HET-s(218-289) molecules in a beta-sheet structure as in the fibril is simulated in aqueous solution. The trajectory structures appear to be consistent with the Calpha chemical shift data obtained. In order to delineate the influence of the beta-sheet core of the fibril upon the structural variability of the loop, the latter is also simulated without the beta-sheet core, but with its N- and C-terminal residues restrained at their positions in the fibril. The analysis of the trajectories shows that the structural variability of the loop is restricted by the beta-sheet core, least at its N-terminal end and most in the middle of the trimer. PMID- 26804446 TI - A functional mesoporous ionic crystal based on polyoxometalate. AB - A mesoporous ionic crystal is synthesized with a polyoxometalate and a macrocation with polar cyano groups. The compound possesses one-dimensional mesopores with an opening of 3.0 * 2.0 nm. The compound shows high proton conductivity and catalytic activity, which are due to the water molecules in the mesopores. PMID- 26804447 TI - Myeloid Sarcoma "en plaque" Disguised as Acute Subdural Hematoma. PMID- 26804450 TI - An intervention to maximize medication management by caregivers of persons with memory loss: Intervention overview and two-month outcomes. AB - Overseeing medication-taking is a critical aspect of dementia caregiving. This trial examined a tailored, problem-solving intervention designed to maximize medication management practices among caregivers of persons with memory loss. Eighty-three community-dwelling dyads (patient + informal caregiver) with a baseline average of 3 medication deficiencies participated. Home- and telephone based sessions were delivered by nurse or social worker interventionists and addressed basics of managing medications, plus tailored problem solving for specific challenges. The outcome of medication management practices was assessed using the Medication Management Instrument for Deficiencies in the Elderly (MedMaIDE) and an investigator-developed Medication Deficiency Checklist (MDC). Linear mixed modeling showed both the intervention and usual care groups had fewer medication management problems as measured by the MedMaIDE (F = 6.91, p < .01) and MDC (F = 9.72, p < .01) at 2 months post-intervention. Reduced medication deficiencies in both groups suggests that when nurses or social workers merely raise awareness of the importance of medication adherence, there may be benefit. PMID- 26804451 TI - A Diradical Approach towards BODIPY-Based Dyes with Intense Near-Infrared Absorption around lambda=1100 nm. AB - A diradical approach to obtain stable organic dyes with intense absorption around lambda=1100 nm is reported. The para- and meta-quinodimethane-bridged BODIPY dimers BD-1 and BD-2 were synthesized and were found to have a small amount of diradical character. These molecules exhibited very intense absorption at lambda=1088 nm (E=6.65*10(5) M(-1) cm(-1) ) and 1136 nm (E=6.44*10(5) M(-1) cm(-1) ), respectively, together with large two-photon-absorption cross-sections. Structural isomerization induced little variation in their diradical character but distinctive differences in their physical properties. Moreover, the compounds showed a selective fluorescence turn-on response in the presence of the hydroxyl radical but not with other reactive oxygen species. PMID- 26804455 TI - A novel lateral flow assay based on GoldMag nanoparticles and its clinical applications for genotyping of MTHFR C677T polymorphisms. AB - Current techniques for single nucleotide polymorphism (SNP) detection require tedious experimental procedures and expensive and sophisticated instruments. In this study, a visual genotyping method has been successfully established via combining ARMS-PCR with gold magnetic nanoparticle (GoldMag)-based lateral flow assay (LFA) and applied to the genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T. C677T substitution of the gene MTHFR leads to an increased risk of diseases. The genotyping result is easily achievable by visual observation within 5 minutes after loading of the PCR products onto the LFA device. The system is able to accurately assess a broad detection range of initial starting genomic DNA amounts from 5 ng to 1200 ng per test sample. The limit of detection reaches 5 ng. Furthermore, our PCR-LFA system was applied to clinical trials for screening 1721 individuals for the C677T genotypes. The concordance rate of the genotyping results detected by PCR-LFA was up to 99.6% when compared with the sequencing results. Collectively, our PCR-LFA has been proven to be rapid, accurate, sensitive, and inexpensive. This new method is highly applicable for C677T SNP screening in laboratories and clinical practices. More promisingly, it could also be extended to the detection of SNPs of other genes. PMID- 26804456 TI - Prediction of pharmacist intention to provide medication disposal education using the theory of planned behaviour. AB - RATIONALE, AIMS AND OBJECTIVES: Lack of familiarity with proper medication disposal options among patients can lead to personal and environmental safety concerns, besides signalling non-adherence. Given that community pharmacists are in a position to educate patients, this study assessed community pharmacists' knowledge on medication disposal and examined the utility of the theory of planned behaviour (TPB) in predicting their intention to provide medication disposal education to their patients. METHODS: A cross-sectional, self administered survey was distributed to community pharmacists in California. Descriptive statistics were reported for all survey items. Cronbach's alpha and Pearson correlation were used to determine the reliability for the four TPB constructs (attitude, subjective norm, perceived behavioural control and intention). Multiple linear regressions were performed to predict intent using the other three TPB constructs. RESULTS: Pharmacists (n = 142) demonstrated a positive intention to provide education (mean = 5.91 +/- 1.22; range: 2 to 8), but most (67.9%) provided this information once a month or less. Attitude (beta = 0.266, P = 0.001), subjective norm (beta = 0.333, P < 0.001) and perceived behavioural control (beta = 0.211, P = 0.009) were significant predictors of intention, accounting for 40.8% of the variance in intention to provide disposal education. Scale reliability ranged from 0.596 to 0.619 for the four constructs. Few pharmacists accurately selected all of the appropriate recommendations of disposal for non-controlled and controlled substances (15.9% and 10.1%, respectively). CONCLUSION: Pharmacists showed favourable attitude, subjective norm, perceived behaviour control and intention in providing such education. However, their knowledge in this area may be lacking and they are not consistently providing this information to their patients. PMID- 26804459 TI - Cowpea (Vigna unguiculata L. Walp), a renewed multipurpose crop for a more sustainable agri-food system: nutritional advantages and constraints. AB - The growing awareness of the relevance of food composition for human health has increased the interest of the inclusion of high proportions of fruits and vegetables in diets. To reach the objective of more balanced diets, an increased consumption of legumes, which constitutes a sustainable source of essential nutrients, particularly low-cost protein, is of special relevance. However, the consumption of legumes also entails some constraints that need to be addressed to avoid a deleterious impact on consumers' wellbeing and health. The value of legumes as a source of nutrients depends on a plethora of factors, including genetic characteristics, agro-climatic conditions, and postharvest management that modulate the dietary effect of edible seeds and vegetative material. Thus, more comprehensive information regarding composition, especially their nutritional and anti-nutritional compounds, digestibility, and alternative processing procedures is essential. These were the challenges to write this review, which focusses on the nutritional and anti-nutritional composition of Vigna unguiculata L. Walp, an emerging crop all over the world intended to provide a rational support for the development of valuable foods and feeds of increased commercial value. (c) 2016 Society of Chemical Industry. PMID- 26804460 TI - Electrochemical Grafting of Graphene Nano Platelets with Aryl Diazonium Salts. AB - To vary interfacial properties, electrochemical grafting of graphene nano platelets (GNP) with 3,5-dichlorophenyl diazonium tetrafluoroborate (aryl-Cl) and 4-nitrobenzene diazonium tetrafluoroborate (aryl-NO2) was realized in a potentiodynamic mode. The covalently bonded aryl layers on GNP were characterized using atomic force microscopy and X-ray photoelectron spectroscopy. Electrochemical conversion of aryl-NO2 into aryl-NH2 was conducted. The voltammetric and impedance behavior of negatively and positively charged redox probes (Fe(CN)63-/4- and Ru(NH3)62+/3+) on three kinds of aryl layers grafted on GNP reveal that their interfacial properties are determined by the charge states of redox probes and reactive terminal groups (-Cl, -NO2, -NH2) in aryl layers. On aryl-Cl and aryl-NH2 garted GNP, selective and sensitive monitoring of positively charged lead ions as well as negatively charged nitrite and sulfite ions was achieved, respectively. Such a grafting procedure is thus a perfect way to design and control interfacial properties of graphene. PMID- 26804461 TI - Impact of active smoking on myocardial infarction severity in reperfused ST segment elevation myocardial infarction patients: the smoker's paradox revisited. AB - AIMS: To investigate the influence of cardiovascular risk factors (CV-RFs) on infarct severity and post-infarction left ventricular (LV) remodelling in acutely reperfused ST-segment elevation myocardial infarction (STEMI) patients studied with cardiovascular magnetic resonance (CMR). METHODS AND RESULTS: Four-hundred seventy-one patients were included in the study. Baseline CMR was performed at 4 +/- 1 days after STEMI to assess area-at-risk, infarct size (IS), myocardial salvage index (MSI), microvascular obstruction (MVO), intramyocardial haemorrhage (IMH), LV volumes, and function. Cardiovascular magnetic resonance was repeated 4 months after STEMI (n = 383) to assess adverse LV remodelling (increase of LV end diastolic volume >20% between baseline and follow-up). Smoking was associated with IMH at baseline even after correction for other factors associated with ischaemia-reperfusion injury including MVO, IS, and MSI (OR: 2.17, 95% CI: 1.17 4.00, P = 0.01). Unexpectedly, smoking was an independent protective predictor against adverse LV remodelling (OR: 0.43, 95% CI: 0.24-0.77, P = 0.005), consistent with the 'smoker's paradox'. However, the presence of IMH at baseline abolished the paradoxical, beneficial effects of smoking with respect to IS, baseline LV function, and post-infarction LV remodelling. No association between other CV-RFs, infarct severity, or post-infarction LV remodelling was observed. CONCLUSION: In patients with reperfused STEMI, smoking is strongly and independently associated with IMH at baseline. Nonetheless, consistent with the 'smoker's paradox', smoking was an independent predictor of more favourable post infarction LV remodelling. However, the paradoxical beneficial effects of smoking were lost in patients with IMH. PMID- 26804463 TI - Microhabitat choice in island lizards enhances camouflage against avian predators. AB - Camouflage can often be enhanced by genetic adaptation to different local environments. However, it is less clear how individual behaviour improves camouflage effectiveness. We investigated whether individual Aegean wall lizards (Podarcis erhardii) inhabiting different islands rest on backgrounds that improve camouflage against avian predators. In free-ranging lizards, we found that dorsal regions were better matched against chosen backgrounds than against other backgrounds on the same island. This suggests that P. erhardii make background choices that heighten individual-specific concealment. In achromatic camouflage, this effect was more evident in females and was less distinct in an island population with lower predation risk. This suggests that behavioural enhancement of camouflage may be more important in females than in sexually competing males and related to predation risk. However, in an arena experiment, lizards did not choose the background that improved camouflage, most likely due to the artificial conditions. Overall, our results provide evidence that behavioural preferences for substrates can enhance individual camouflage of lizards in natural microhabitats, and that such adaptations may be sexually dimorphic and dependent on local environments. This research emphasizes the importance of considering links between ecology, behaviour, and appearance in studies of intraspecific colour variation and local adaptation. PMID- 26804464 TI - Different Binding Modes of Small and Large Binders of GAT1. AB - Well-known inhibitors of the gamma-aminobutyric acid (GABA) transporter GAT1 share a common scaffold of a small cyclic amino acid linked by an alkyl chain to a moiety with two aromatic rings. Tiagabine, the only FDA-approved GAT1 inhibitor, is a typical example. Some small amino acids such as (R)-nipecotic acid are medium-to-strong binders of GAT1, but similar compounds, such as proline, are very weak binders. When substituted with 4,4-diphenylbut-3-en-1-yl (DPB) or 4,4-bis(3-methylthiophen-2-yl)but-3-en-1-yl (BTB) groups, the resulting compounds have similar pKi and pIC50 values, even though the pure amino acids have very different values. To investigate if small amino acids and their substituted counterparts share a similar binding mode, we synthesized butyl-, DPB , and BTB-substituted derivatives of small amino acids. Supported by the results of docking studies, we propose different binding modes not only for unsubstituted und substituted, but also for strong- and weak-binding amino acids. These data lead to the conclusion that following a fragment-based approach, not pure but N butyl-substituted amino acids should be used as starting points, giving a better estimate of the activity when a BTB or DPB substituent is added. PMID- 26804465 TI - Testicular effects of 3-nitro-1,2,4-triazol-5-one (NTO) in mice when exposed orally. AB - 3-Nitro-1,2,4-triazol-5-one (NTO) is currently being investigated in the development of insensitive munitions. Rats orally exposed to NTO have demonstrated testicular toxicity in both subacute and subchronic studies; however, toxicity has not been verified in mice. Also, previous studies have not demonstrated the nature of NTO-induced testicular toxicity due to the prolonged dosing regimen utilized and effects of maturation depletion. In this study, a time-course design was used and the earliest pathological changes in testes of adult BALB/c mice orally dosed with NTO in corn oil suspensions at 0, 500 or 1000 mg/kg-day NTO for 1, 3, 7 or 14 d were evaluated. The earliest NTO-induced testicular changes occurred in the 1000 mg/kg-day group at day 7 and the 500 mg/kg-day group at day 14 as evident by the presence of bi- and multinucleated giant cells (MNGCs) of almost all spermatids in an isolated stage II-III tubule/step 2-3 and a stage IX tubule/step 9 in the 1000 and 500 mg/kg-day groups, respectively. Testicular toxicity was characterized by degeneration and the presence of bi- and MNGCs of spermatids (stages II-III and IX), which progressed to additional germ cell degeneration as dosing duration increased. Occasional step 16 spermatid retention was also noted in stage XII and I tubules in the day 14, 1000 mg/kg-day group. These data indicate that NTO is a testicular toxicant in mice and that spermatids are the most sensitive cell. The presence of retained spermatids warrants further investigation regarding NTO's role as a direct Sertoli cell toxicant. PMID- 26804467 TI - Foot contact angle variability during a prolonged run with relation to injury history and habitual foot strike pattern. AB - Foot strike pattern and movement variability have each been associated with running injuries. Foot contact angle (FCA) is a common measure of strike pattern. Thus, variability in FCA could be an important running injury risk factor. The purposes of this study were to compare (a) foot contact angle (FCA) and its variability between runners with and without injury history and, (b) FCA variability between habitual rearfoot strike (RFS) and non-RFS runners during a prolonged run. Twenty-three runners with and 21 without injury history participated. Motion capture was used to collect kinematic data during a 40 min treadmill run. Average FCA and its variability were compared between injury groups and among four time points. FCA and its variability were not different between runners with and without injury history or among time points during the run. FCA variability was lower in non-RFS compared to RFS runners (P < 0.001). Lower FCA variability in non-RFS runners may have implications for higher injury risks due to repeated localized tissue loading. Prospective analyses on the effects of lower FCA variability on injury risk are needed. PMID- 26804466 TI - Glucose restriction induces transient G2 cell cycle arrest extending cellular chronological lifespan. AB - While glucose is the fundamental source of energy in most eukaryotes, it is not always abundantly available in natural environments, including within the human body. Eukaryotic cells are therefore thought to possess adaptive mechanisms to survive glucose-limited conditions, which remain unclear. Here, we report a novel mechanism regulating cell cycle progression in response to abrupt changes in extracellular glucose concentration. Upon reduction of glucose in the medium, wild-type fission yeast cells undergo transient arrest specifically at G2 phase. This cell cycle arrest is dependent on the Wee1 tyrosine kinase inhibiting the key cell cycle regulator, CDK1/Cdc2. Mutant cells lacking Wee1 are not arrested at G2 upon glucose limitation and lose viability faster than the wild-type cells under glucose-depleted quiescent conditions, suggesting that this cell cycle arrest is required for extension of chronological lifespan. Our findings indicate the presence of a novel cell cycle checkpoint monitoring glucose availability, which may be a good molecular target for cancer therapy. PMID- 26804469 TI - Graphite-Conjugated Rhenium Catalysts for Carbon Dioxide Reduction. AB - Condensation of fac-Re(5,6-diamino-1,10-phenanthroline)(CO)3Cl to o-quinone edge defects on graphitic carbon surfaces generates graphite-conjugated rhenium (GCC Re) catalysts that are highly active for CO2 reduction to CO in acetonitrile electrolyte. X-ray photoelectron and X-ray absorption spectroscopies establish the formation of surface-bound Re centers with well-defined coordination environments. GCC-Re species on glassy carbon surfaces display catalytic currents greater than 50 mA cm(-2) with 96 +/- 3% Faradaic efficiency for CO production. Normalized for the number of Re active sites, GCC-Re catalysts exhibit higher turnover frequencies than that of a soluble molecular analogue, fac-Re(1,10 phenanthroline)(CO)3Cl, and turnover numbers greater than 12,000. In contrast to the molecular analogue, GCC-Re surfaces display a Tafel slope of 150 mV/decade, indicative of a catalytic mechanism involving rate-limiting one-electron transfer. This work establishes graphite-conjugation as a powerful strategy for generating well-defined, tunable, heterogeneous electrocatalysts on ubiquitous graphitic carbon surfaces. PMID- 26804470 TI - Neutrophil extracellular traps are associated with inflammation in chronic airway disease. AB - BACKGROUND AND OBJECTIVE: Neutrophil extracellular traps (NETs) are web-like structures comprising DNA and antimicrobial proteins, expelled from neutrophils during NETosis. Persistence of NETs can be pro-inflammatory, yet their role in respiratory disease remains unclear. This study aimed to investigate the presence of NETs in sputum from patients with asthma and COPD, and the relationship of NETs with inflammatory phenotype and disease severity. METHODS: Induced sputum was collected from healthy controls, asthma and COPD patients. Extracellular DNA (eDNA) was quantified by PicoGreen. LL-37, alpha-defensins1-3, NE, IL-1beta and CXCL8 were quantified by ELISA. PAD4 and NLRP3 gene expression was performed using qPCR. NETs were imaged in sputum smears using immunofluorescence microscopy. RESULTS: Sputum eDNA and NET neutrophil antimicrobial proteins were significantly elevated in asthma and COPD compared with healthy controls. Levels of eDNA and NET components were significantly higher in neutrophilic versus non neutrophilic asthma and COPD. NETs were clearly visualized in sputum smears. PAD4 mRNA was upregulated in neutrophilic COPD. The level of eDNA was higher in severe asthma. High eDNA levels were associated with heightened innate immune responses, including elevated CXCL8 and IL-1beta, and NLRP3 gene expression in both COPD and asthma. Antimicrobial proteins and eDNA were positively correlated with airway neutrophils, and negatively correlated with lung function and symptoms. CONCLUSION: NETs are present in the airways of subjects with asthma and COPD. Accumulation of excessive NETs was associated with activation of innate immune responses contributing to disease pathogenesis in chronic airway disease. PMID- 26804473 TI - Evaluation of a novel automated volumetric flow cytometer for absolute CD4+ T lymphocyte quantitation. AB - BACKGROUND: Bead-based single platform cytometry technology (SPT) is the gold standard when performing CD4 absolute counting. However, it presents drawbacks as precision depends on various critical steps (for example, pipetting methodology, overtime stability of beads, stability of fluidics, regular recalibration...) and thus requires skilled operators. The fully automated volumetric SPT AQUIOS CL (Beckman Coulter) has recently emerged as an alternative with no need of beads. It may help improving results standardisation and fulfilling requirements for certification (ISO 15189). In this study, we assessed SPT AQUIOS CL performances in accordance to requirements for ISO 15189 accreditation. METHODS: We evaluated repeatability and reproducibility (precision), bias (trueness), uncertainty (total error), range limits (linearity, quantification, detection limits), and inter-reagent/inter-sample contaminations in enumerating CD4+ T-cells. Concomitantly, we compared AQUIOS CL CD4+ T-cell values with the results obtained with our routine bead-based SPT (that is, FC500 Beckman Coulter, bead-based SPT), on blood samples from 148 patients representative of clinical laboratory routine workload. RESULTS: Every result (repeatability, reproducibility, trueness, total error) was below the acceptable thresholds proposed in international recommendations. Contamination results and range limits (linearity, quantification, and detection limits) were all found perfectly suitable to routine analysis. The comparison between AQUIOS CL and FC500 exhibited excellent correlation and agreement (Pearson R = 0.99, P < 0.001; Lin's concordance correlation coefficient: Lin rhoc = 0.991, Cb = 0.999), and Bland-Altman analysis did not reveal any systematic error. CONCLUSIONS: Our results demonstrate that, upon subsequent validation in more routine conditions, the AQUIOS CL could be a suitable tool for clinical flow cytometry laboratories facing accreditation process. (c) 2016 International Clinical Cytometry Society. PMID- 26804474 TI - Oligothiophene wires: impact of torsional conformation on the electronic structure. AB - Charge transport in polymer- and oligomer-based semiconductor materials depends strongly on the structural ordering of the constituent molecules. Variations in molecular conformations influence the electronic structures of polymers and oligomers, and thus impact their charge-transport properties. In this study, we used Scanning Tunneling Microscopy and Spectroscopy (STM/STS) to investigate the electronic structures of different alkyl-substituted oligothiophenes displaying varied torsional conformations on the Au(111) surface. STM imaging showed that on Au(111), oligothiophenes self-assemble into chain-like structures, binding to each other via interdigitated alkyl ligands. The molecules adopted distinct planar conformations with alkyl ligands forming cis- or trans- mutual orientations. For each molecule, by using STS mapping, we identify a progression of particle-in-a-box-like states corresponding to the LUMO, LUMO+1 and LUMO+2 orbitals. Analysis of STS data revealed very similar unoccupied molecular orbital energies for different possible molecular conformations. By using density functional theory calculations, we show that the lack of variation in molecular orbital energies among the different oligothiophene conformers implies that the effect of the Au-oligothiophene interaction on molecular orbital energies is nearly identical for all studied torsional conformations. Our results suggest that cis-trans torsional disorder may not be a significant source of electronic disorder and charge carrier trapping in organic semiconductor devices based on oligothiophenes. PMID- 26804476 TI - Response letter regarding the letter to the editors by Butt et al. Does it matter Discounting and its role in the cost-effectiveness of preventative interventions. The case of HPV vaccination. PMID- 26804478 TI - The role of PD-L1 in the radiation response and clinical outcome for bladder cancer. AB - Identification of potential factors that can stratify a tumor's response to specific therapies will aid in the selection of cancer therapy. The aim was to highlight the role of programmed cell death 1 ligand 1 (PD-L1) in bladder cancer. In this study, 92 of muscle-invasive bladder cancers and 28 of non-muscle invasive bladder cancers were selected for immunohistochemical staining analysis. Furthermore, human and murine bladder cancer cell lines were used to examine the correlation between PD-L1 and radiation response. Our data revealed that PD-L1 was overexpressed in the bladder tumor specimens compared with adjacent non malignant specimens. Furthermore, the staining of PD-L1 was significantly linked to higher clinical stage, lower complete response rates and reduced disease-free survival rates. By in vitro and in vivo experiments, irradiation up-regulated the expression of PD-L1 in tumor cells, and its increase correlated with the irradiation dose. In immunocompetent mouse models, blocking PD-L1 induced a longer tumour growth delay following irradiation. The inhibition of T cell functions including proliferation and cytotoxicity against tumor cells was responsible to the effects of PD-L1 on radiation response. In conclusion, PD-L1 could be a significant clinical predictor for clinical stage and treatment response of bladder cancer. PMID- 26804479 TI - Solubilization and Iterative Saturation Mutagenesis of alpha1,3 fucosyltransferase from Helicobacter pylori to enhance its catalytic efficiency. AB - alpha1,3-Fucosyltransferase (alpha1,3-FucT) is essential for the biosynthesis of biologically active alpha1,3-fucosyloligosacchairdes (3-FOs) from human milk oligosaccharides (HMO), particularly 3-fucosyllactose (3-FL) trisaccharide. alpha1,3-FucT from Helicobacter pylori 26695 (FutA) accepts lactose and LacNAc as glycan acceptors and has a very low level of expression in Escherichia coli, and it shows a low catalytic activity for lactose in the large-scale synthesis of 3 FL. To overcome the poor solubility of FutA, codon optimization, and systematic truncation of the protein at the C-terminus with only one heptad repeat remaining (Delta52 FutA) were conducted to yield 150-200 mg/L of soluble protein of FutA and resulting in more than an 18-fold increase in the 3-FL yield. To improve the low level of enzyme catalytic activity for lactose, focused directed evolution was attempted using a semi-rational approach that combines structure-guided computational analysis and subsequent iterative saturation mutagenesis (ISM). In order to select the functional residues in active site/substrate binding site, docking simulation was used together with HotSpot Wizard to target evolutionarily variable amino acid positions. A128 site was selected from the key residue located in the active site, and A128N mutant displayed a 3.4-fold higher catalytic activity than wild-type Delta52 FutA. Considering that the A128N mutation is located in the deep cleft of the lactose binding site, the residues within the substrate binding sites, especially on the two alpha-helices for lactose and one alpha-helix for GDP-fucose, were subjected to structure-guided ISM. The selected residues from each helix were clustered, and ISM was performed for each cluster in parallel. In particular, the mutant with triple mutations (A128N/H129E/Y132I) located on the alpha5 helix exhibited a 9.6-fold improvement in specific activity when compared to wild-type Delta52 FutA. When such clustered mutations on two alpha-helices (alpha5 and alpha2/loop) were combined, mutants with triple (A128N/H129E/S46F) and quadruple mutations (A128N/H129E/Y132I/S46F) were generated, which showed the synergistic effects, that is 14.5- and 15.5-fold improvement in specific activity relative to wild-type Delta52 FutA, respectively. The mutations increased their binding affinity for lactose and kcat values for lactose and GDP-fucose. The Delta52 FutA quadruple mutant (A128N/H129E/Y132I/S46F) was successfully applied to in vitro synthesis of 3-FL with an improved yield and productivity (>96% yield based on 5 mM of GDP-Fuc within 1 h). Biotechnol. Bioeng. 2016;113: 1666-1675. (c) 2016 Wiley Periodicals, Inc. PMID- 26804480 TI - Lipopolysaccharide-binding protein is bound and internalized by host cells and colocalizes with LPS in the cytoplasm: Implications for a role of LBP in intracellular LPS-signaling. AB - The lipopolysaccharide-binding protein (LBP) is critically involved in innate immune responses to Gram-negative infections. We show here that human peripheral blood-derived monocytes, but not lymphocytes, stain positive for endogenous LBP on the cell surface. Studies on human macrophages demonstrate LBP binding at normal serum concentrations of 1-10 MUg/ml. Binding was increased in a concentration-dependent manner by lipopolysaccharide (LPS). Fluorescence quenching experiments and confocal microscopy revealed constitutive and LPS induced internalization of LBP by macrophages. Experiments with macrophages and HEK293 cell lines showed that binding and uptake of LBP do not depend on the LPS receptors CD14 and TLR4/MD-2. Fractionation of Triton X-100 solubilized cytoplasmic membranes revealed that LBP was primarily localized in non-raft domains under resting conditions. Cellular LPS stimulation elevated LBP levels and induced enrichment in fractions marking the transition between non-raft and raft domains. LBP was found to colocalize with LPS at the cytoplasmic membrane and in intracellular compartments of macrophages. In macrophages stimulated with LPS and ATP for inflammasome activation, LBP was observed in close vicinity to activated caspases. Furthermore, LBP conferred IL-1beta production by LPS in the absence of ATP. These data establish that LBP serves not only as an extracellular LPS shuttle but in addition facilitates intracellular transport of LPS. This observation adds a new function to this central immune regulator of LPS biology and raises the possibility for a role of LBP in the delivery of LPS to TLR4 independent intracellular receptors. PMID- 26804481 TI - Ca(2+) microdomains, NAADP and type 1 ryanodine receptor in cell activation. AB - Nicotinic acid adenine dinucleotide phosphate (NAADP) is a Ca(2+) mobilizing second messenger that belongs to the superfamily of regulatory adenine nucleotides. Though NAADP has been known since 20 years, several aspects of its metabolism and molecular mode of action are still under discussion. Though the importance of the type 1 ryanodine receptor was discovered and published already in 2002 Hohenegger et al. (2002 Oct 15), recent data re-emphasize these original findings in pancreatic acinar cells and in T-lymphocytes. Here we review recent developments in NAADP formation and metabolism, putative target Ca(2+) channels for NAADP with special emphasis on the type 1 ryanodine receptor, and NAADP binding proteins. The latter are basis for a unifying hypothesis for NAADP action. Finally, the role of NAADP in T cell Ca(2+) signaling and activation is discussed. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen. PMID- 26804483 TI - A Geriatric Perspective on Benign Paroxysmal Positional Vertigo. AB - Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo in older adults. Beyond the unpleasant sensation of vertigo, BPPV also negatively affects older adults' gait and balance and increases their risk of falling. As such it has a profound effect on function, independence, and quality of life. Otoconia are the inner ear structures that help detect horizontal and vertical movements. Aging contributes to the fragmentation of otoconia, whose displacement into the semicircular, most commonly posterior canals, can produce rotatory movement sensations with head movement. BPPV is more commonly idiopathic in older adults than in younger individuals, can present atypically, and has a more protracted course and higher risk of recurrence. Medications such as meclizine that are commonly prescribed for BPPV can be associated with significant side effects. Dix-Hallpike and Head Roll tests can generally identify the involved canal. Symptoms resolve as otoconia fragments dissolve into the endolymph, but appropriate canalith repositioning (e.g., Epley maneuver) can expedite recovery and reduce the burden of this disorder. Observations suggesting an association between idiopathic BPPV and vitamin D deficiency and osteoporosis indicate that BPPV may share risk factors with other common geriatric conditions, which highlights the importance of moving beyond purely otological considerations and addressing the needs of older adults with vertigo through a systems-based multidisciplinary approach. PMID- 26804484 TI - An analysis of observer-rated functional vision in patients implanted with the Argus II Retinal Prosthesis System at three years. AB - OBJECTIVE: The purpose of this analysis was to compare observer-rated tasks in patients implanted with the Argus II Retinal Prosthesis System, when the device is ON versus OFF. METHODS: The Functional Low-Vision Observer Rated Assessment (FLORA) instrument was administered to 26 blind patients implanted with the Argus II Retinal Prosthesis System at a mean follow-up of 36 months. FLORA is a multi component instrument that consists in part of observer-rated assessment of 35 tasks completed with the device ON versus OFF. The ease with which a patient completes a task is scored using a four-point scale, ranging from easy (score of 1) to impossible (score of 4). The tasks are evaluated individually and organised into four discrete domains, including 'Visual orientation', 'Visual mobility', 'Daily life and 'Interaction with others'. RESULTS: Twenty-six patients completed each of the 35 tasks. Overall, 24 out of 35 tasks (69 per cent) were statistically significantly easier to achieve with the device ON versus OFF. In each of the four domains, patients' performances were significantly better (p < 0.05) with the device ON versus OFF, ranging from 19 to 38 per cent improvement. CONCLUSION: Patients with an Argus II Retinal Prosthesis implanted for 18 to 44 months (mean 36 months), demonstrated significantly improved completion of vision related tasks with the device ON versus OFF. PMID- 26804485 TI - Reliability of Ultrasound Diameter Measurements in Patients with a Small Asymptomatic Popliteal Artery Aneurysm: An Intra- and Inter-observer Agreement Study. AB - BACKGROUND: In this study the intra- and inter-observer variability of ultrasound measurements of the diameter of the popliteal artery were tested in a group of patients under surveillance for a small (diameter 10-20 mm), asymptomatic popliteal artery aneurysm (PAA). METHODS: From a group of patients under ultrasound surveillance for bilateral, asymptomatic PAAs, 13 consecutive patients agreed to participate in the study and provided informed consent. The maximum diameter of the popliteal arteries was assessed by a vascular technologist. The same assessment was repeated by a second vascular technologist, unaware of the results of the first measurement. After a week, this protocol was repeated. The intra- and inter-observer reliability of this measurement was calculated using intra-class correlation coefficients (ICCs) and Bland and Altman plots. RESULTS: Of the 10 patients with bilateral and three patients with unilateral PAA, 12 completed the 2 week protocol. A total of 86 measurements were analyzed. The mean diameter of the popliteal arteries was 13.5 +/- 3.4 mm. The ICC for the intra observer reliability of observer 1 was 0.96 (95% CI 0.92-0.99), p < .001 and of observer 2 was 0.98 (95% CI 0.95-0.99), p < .001. The ICC for the inter-observer reliability for the first measurements was 0.96 (95% CI 0.90-0.98), p < .001 and for the second measurements 0.97 (95% CI 0.94-0.99), p < .001. The Bland-Altman plots showed random error, while 95% of the variation was between 0.016 and 0.16, p > .47. The absolute magnitude of the systematic error of both observers was less than 0.135 mm (median 0.00). CONCLUSION: Ultrasound measurement of the maximum diameter of the popliteal artery is reproducible; hence, it is suitable for making a clinical treatment decision. Its use for surveillance of small, asymptomatic PAAs is justified. PMID- 26804486 TI - Cancer patients' referral wish: effects of distress, problems, socio-demographic and illness-related variables and social support sufficiency. AB - BACKGROUND: The present study's aim was to examine effects of cancer patients' perceived distress and problems, socio-demographic and illness-related variables and social support sufficiency on referral wish. METHODS: A cross-sectional group of 1340 patients (response = 51%) completed a questionnaire consisting of the Dutch version of the Distress Thermometer and Problem List, including the referral wish question, and questions on socio-demographic and illness-related variables and perceived social support sufficiency. Univariate and multivariate analyses were performed to investigate the effects of these variables on patients' referral wish. RESULTS: Of the patients who completed the referral wish question (N = 1297), 13% wished and 21% considered a referral, while 66% did not want a referral. Univariate analyses showed that, in comparison with patients not having a referral wish, those having a (maybe) wish were more distressed, reporting more problems in all Problem List domains, younger, more likely not to have children or children living at home, higher educated, more likely to be employed, under active treatment or recently diagnosed, receiving more intensive treatment and more likely to perceive support received to be insufficient. A final ordinal logistic regression analysis showed independent effects of distress, practical and emotional problems, age and treatment phase on referral wish (chi2 (6) = 205.9; p < 0.001; Nagelkerke's R2 = 0.24). CONCLUSIONS: A third of the patients (maybe) wished a referral. Knowledge of risk variables (particularly increased distress, experience of more practical and emotional problems, younger age and receiving active treatment or recently diagnosed) may support the identification of patients at increased need of additional healthcare services. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26804487 TI - Effects of acute critical illnesses on the performance of interferon-gamma release assay. AB - Performance of interferon-gamma release assays (IGRAs) is influenced by preanalytical, laboratory and host factors. The data regarding how critical illnesses influence IGRA results are limited. This study aimed to investigate IGRA performance among critically ill patients. Patients admitted to intensive care unit (ICU) were prospectively enrolled, and underwent QuantiFERON-TB Gold In Tube testing on admission and discharge. The associations between patient factors and IGRA results were explored. In total, 118 patients were included. IGRA results on admission were positive, negative and indeterminate for 10 (9%), 36 (31%) and 72 (61%) patients. All indeterminate results were due to a low mitogen response. Indeterminate results were associated with higher disease severity and lower serum albumin levels. Ninety (76%) patients survived to ICU discharge and had repeat IGRA testing 13.3 +/- 10.1 days after first ones. Of those, 43 (48%) had indeterminate results, and no IGRA conversion or reversion was observed. The majority (35/51, 69%) of ICU survivors with initial indeterminate results still had indeterminates on follow-up testing. Acute critical illnesses exert a significant impact on IGRA performance and a high proportion of indeterminate results was seen in ICU patients. This study highlights limitation of IGRAs in the critically ill and judicious selection of patients to be tested should be considered. PMID- 26804488 TI - Model of anaesthetic induction by unilateral intracerebral microinjection of GABAergic agonists. AB - General anaesthetic agents induce loss of consciousness coupled with suppression of movement, analgesia and amnesia. Although these diverse functions are mediated by neural structures located in wide-ranging parts of the neuraxis, anaesthesia can be induced rapidly and reversibly by bilateral microinjection of minute quantities of gamma-aminobutyric acid (GABA)A -R agonists at a small, focal locus in the mesopontine tegmentum (MPTA). State switching under these circumstances is presumably executed by dedicated neural pathways and does not require widespread distribution of the anaesthetic agent itself, the classical assumption regarding anaesthetic induction. Here it was asked whether these pathways serve each hemisphere independently, or whether there is bilateral redundancy such that the MPTA on each side is capable of anaesthetizing the entire brain. Either of two GABAA -R ligands were microinjected unilaterally into the MPTA in awake rats, the barbiturate modulator pentobarbital and the direct receptor agonist muscimol. Both agents, microinjected on either side, induced clinical anaesthesia, including bilateral atonia, bilateral analgesia and bilateral changes in cortical activity. The latter was monitored using c-fos expression and electroencephalography. This action, however, was not simply a consequence of suppressing spike activity in MPTA neurons, as unilateral (or bilateral) microinjection of the local anaesthetic lidocaine at the same locus failed to induce anaesthesia. A model of the state-switching circuitry that accounts for the bilateral action of unilateral microinjection and also for the observation that inactivation with lidocaine is not equivalent to inhibition with GABAA -R agonists was proposed. This is a step in defining the overall switching circuitry that underlies anaesthesia. PMID- 26804489 TI - A modular force-controlled robotic instrument for minimally invasive surgery - efficacy for being used in autonomous grasping against a variable pull force. AB - BACKGROUND: Many deficiencies of minimally invasive robotic surgery systems can be eliminated by using automated laparoscopic tools with force measurement and control capability. METHOD: A fully modular, automated laparoscopic instrument with a proximal force sensory system was designed and fabricated. The efficacy of the instrument was evaluated experimentally when functioning in an autonomous force-controlled grasping scheme. RESULTS: The designed instrument was shown to work easily with standard laparoscopic tools, with the whole distal part detachable for autoclave sterilization. The root mean squared error (RMSE) of the actual pinch force from the target ramp was 0.318 N; it was 0.402 N for a sinusoidal pull force, which dropped by 21% using a static friction compensation. A secure grasping condition was achieved, in spite of this error, by applying a sufficiently large margin from the slip boundary. CONCLUSIONS: With a simple and practical design, the instrument enjoys affordability, versatility and autoclave sterilizability for clinical usage, with an acceptable performance for being used in an auto-grasping control scheme. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26804491 TI - A fluorescent molecular capsule with a flexible polyaromatic shell for the detection of monoterpene compounds in water. AB - A new molecular capsule with a flexible fluorescent shell was formed by the quantitative self-complementary assembly of amphiphilic, U-shaped polyaromatic subunits in water. The capsule can fully encapsulate a variety of non-fluorescent monoterpene compounds (e.g., menthone, menthol, and p-menthane) in the hydrophobic cavity and act as a fluorescent supramolecular probe for recognizing the structural identity of the analytes by emissive signals in water at room temperature. PMID- 26804492 TI - Global effects of local food-production crises: a virtual water perspective. AB - By importing food and agricultural goods, countries cope with the heterogeneous global water distribution and often rely on water resources available abroad. The virtual displacement of the water used to produce such goods (known as virtual water) connects together, in a global water system, all countries participating to the international trade network. Local food-production crises, having social, economic or environmental origin, propagate in this network, modifying the virtual water trade and perturbing local and global food availability, quantified in terms of virtual water. We analyze here the possible effects of local crises by developing a new propagation model, parsimonious but grounded on data-based and statistically-verified assumptions, whose effectiveness is proved on the Argentinean crisis in 2008-09. The model serves as the basis to propose indicators of crisis impact and country vulnerability to external food-production crises, which highlight that countries with largest water resources have the highest impact on the international trade, and that not only water-scarce but also wealthy and globalized countries are among the most vulnerable to external crises. The temporal analysis reveals that global average vulnerability has increased over time and that stronger effects of crises are now found in countries with low food (and water) availability. PMID- 26804493 TI - A Population Focused Approach to Mental Health Care as a Complement to Person Centered Care. PMID- 26804490 TI - Association Between Meat and Meat-Alternative Consumption and Iron Stores in Early Childhood. AB - OBJECTIVE: To prevent iron deficiency, 2014 Canadian recommendations for healthy term infants from 6 to 24 months recommend iron-rich complementary foods such as meat and meat alternatives 2 or more times a day. The purpose of our study was to evaluate the association between meat and meat-alternative consumption and iron status in young children and the association between red meat consumption and iron status among children meeting recommendations. METHODS: Healthy children aged 12 to 36 months were recruited. A cross-sectional study was conducted. Meat and meat-alternative consumption was measured using the NutriSTEP questionnaire. Adjusted multivariable regression analyses were used to evaluate an association between meat consumption and serum ferritin, and iron deficiency (serum ferritin <14 MUg/L). RESULTS: A total of 1043 children were included. Seventy-three percent of children met the recommended daily intake of meat and meat alternatives, and 66% ate red meat in the past 3 days. Eating meat and meat alternatives was not associated with serum ferritin (0.13 MUg/L, 95% confidence interval -0.05, 0.31, P = .16), but it was associated with a decreased odds of iron deficiency (odds ratio 0.97, 95% confidence interval 0.94, 0.99, P = .03). Associations between red meat consumption and iron status were not statistically significant. Statistically significant covariates associated with increased odds of iron deficiency included longer breast-feeding duration, daily cow's milk intake of >2 cups, and a higher body mass index z score. CONCLUSIONS: Daily cow's milk intake of >2 cups, longer breast-feeding duration, and a higher body mass index z score were modifiable risk factors associated with iron deficiency. Eating meat according to recommendations may be a promising additional target for the prevention of iron deficiency in early childhood. PMID- 26804494 TI - Prevalence of Suicide Risk Among Adolescents With Depressive Symptoms. AB - OBJECTIVE: To determine the prevalence of the risk of suicide among adolescents and to investigate associations between the risk of suicide and depressive symptoms. METHODS: A population-based cross-sectional study was conducted with 1,379 students aged 10-17 years enrolled in state-run public schools in northeastern Brazil in 2014. The following instruments were used to collect data: a socio-bio-demographic questionnaire; the Children's Depression Inventory (CDI) and the International Neuropsychiatric Interview (M.I.N.I. Brazilian version 5.0.0). Unidimensional and bidimensional tables were constructed for the data analysis, with absolute and relative frequencies. Odds ratios (OR) and respective intervals (95% confidence) were calculated and associated with the descriptive levels of Pearson's chi-square independence test. RESULTS: The prevalence of the risk of suicide was 29.7% in the population studied. Females aged between 14 and 17, those with siblings and those with depressive symptoms were at the greatest risk. CONCLUSION: The present findings revealed a very high risk of suicide and confirmed the significant that depressive symptoms are significantly associated with the risk of suicide among adolescents. Thus, it is necessary to develop suicide prevention programs for schools, with interdisciplinary primary healthcare actions. PMID- 26804495 TI - Racial and Ethnic Differences in Prenatal Life Stress and Postpartum Depression Symptoms. AB - This study determined the risk of core depression symptoms based on life stress domains during pregnancy and whether stressors varied by race/ethnicity. The sample consisted of 2,344 White, African American, Hispanic, and Asian/Pacific Islander (API) Massachusetts women who recently gave birth. African Americans and Hispanics who endorsed high relational and high financial stress were more likely to report high depressed mood and loss of interest; high physical stress was associated with high depressed mood among API. Screening based on life stress domains may be informative in determining risk for core depression symptoms during the postpartum period especially for minority groups. PMID- 26804496 TI - The Mediating Effects of Positive Cognitions on Autism Caregivers' Depression and Their Children's Challenging Behaviors. AB - Caregivers of persons with Autism Spectrum Disorders (ASD) are prone to depression and psychological problems, which have an impact on their children's challenging behaviors. Positive cognitions include specific positive thinking patterns that enhance one's ability to effectively manage daily activities and promote mental health. The purpose of this research is to test the mediating effects of positive cognitions on the relationship between caregivers' depression and their children's challenging behaviors among 117 caregivers of persons with ASD. Positive cognitions were found to have mediating effects on the relationship between caregiver's depression and their children's challenging behaviors in this sample of caregivers of persons with ASD. Nurses are in a strategic position to include in their interventions those strategies that strengthen positive cognitions in order to improve the caregivers' positive cognitions and well being, which, in turn will have an impact on their children's challenging behaviors. PMID- 26804497 TI - Efficacy of a Culturally Tailored Therapeutic Intervention Program for Community Dwelling Depressed Korean American Women: A Non-Randomized Quasi-Experimental Design Study. AB - BACKGROUND: Asian American women are more prone to suffer from depression compared to their non-Asian American counterparts and have lower rates of seeking mental healthcare services due to lack of available culturally appropriate therapies. Two prior studies of a culturally tailored therapeutic intervention called LogoAutobiography were helpful in treating depressed Korean American women. The LogoAutobiography program was revised to enhance its efficacy not only for depressive symptoms and purpose in life but also to increase coping strategies. OBJECTIVES: To test the efficacy of the Enhanced LogoAutobiography program on depressive symptoms, purpose in life, and coping strategies of depressed community-dwelling Korean American women. DESIGN: Two-group, non randomized quasi-experimental design. SETTINGS: Local Korean community areas located in New York City and eastern New Jersey of the United States. PARTICIPANTS: A total of 54 depressed women with Korean heritage completed either experimental group (n1=25) or control group (n2=29). Sample inclusion criteria were adult women with Korean heritage, depressive symptoms as measured by a CES-D score 16 or higher, fluent Korean language, and able to participate independently. Sample exclusion criteria were those who presented active suicidal ideation and history of episodes of mania or psychosis screened by the psychosocial survey questionnaire. METHODS: The experimental group received Enhanced Logo-Autobiography program which was guided by a facilitator who used a manualized intervention for 90minute sessions over 8weeks; the control group attended routine weekly community activities. Data were collected during the first session (pretest), the end of 8weeks (posttest), and the 3months follow-up session. Time and group changes in depressive symptoms, purpose in life, and coping strategies were computed using Repeated Measures General Linear Model (RMGLM). RESULTS: Findings suggested that the experimental group showed greater improvement in depressive symptoms (F=6.94 (2, 88), p<0.01), active cognitive coping (F=5.07 (2, 86), p<0.01), and avoidance coping strategies (F=3.48 (2, 86), p<0.05) compared to the control group during the three time intervals. Purpose in life showed statistically significant Time and Group effects (F=5.18 (2, 88), p<0.01; F=9.44 (2, 88), p<0.01, respectively), but no significant interaction effect of Time and Group was detected. CONCLUSION: These findings suggest that enhanced LogoAutobiography is effective for depressive symptoms and coping strategies and somewhat effective for improving purpose in life for depressed Korean American women. PMID- 26804499 TI - An Emotional Awareness Based Parenting Group for Parents with Mental Illness: A Mixed Methods Feasibility Study of Community Mental Health Nurse Facilitation. AB - There has been limited examination of the use of relationship based structured parenting programs that focus on emotional interactions in the parent-child dyad in families where a parent has a mental illness. There is also a lack of awareness of the practicalities of providing such interventions within adult mental health services. This study explores the process and outcomes of a nurse led emotional awareness based parenting program for adult clients of a mental health service. Participants demonstrated a significant reduction in difficult parenting moments and associated stress and distress as well as promising improvements in overall distress and emotional awareness. PMID- 26804498 TI - Depression, Social Isolation, and the Lived Experience of Dancing in Disadvantaged Adults. AB - This qualitative study described the lived experience of dancing as it related to depression and social isolation in 16 disadvantaged adults who completed a 12 week dance intervention. It is the first qualitative study to explore the experience of dance as an adjunct therapy, depression, and social isolation. A descriptive phenomenological framework consisted of two focus groups using semi structured interviews. A Giorgian approach guided thematic analysis. Four themes emerged: (1) dance for myself and health, (2) social acceptance, (3) connection with others: a group, and (4) not wanting to stop: unexpected benefits from dancing. As the participants continued to dance, they developed a sense of belonging and group identity, which may have maintained group involvement and contributed to reducing depression and social isolation. Thus, dancing is a complementary therapy that should be considered when working with adults with depression and social isolation. PMID- 26804500 TI - Comparison of the Quality of Life, Perceived Stigma and Medication Adherence of Chinese with Schizophrenia: A Follow-Up Study. AB - OBJECTIVES: The community-based mental health services were encouraged to improve the quality of life for individuals with chronic mental disorders in Mainland China. This study aims to explore how the quality of life, perceived stigma, and medication adherence differ among a Chinese population with schizophrenia prior to and one-month following discharge. METHOD: One hundred and twenty-eight Chinese people with schizophrenia completed the self-report scales: the Schizophrenia Quality of Life Scale (SQLS), the Link' Stigma Scale, and the Morisky Medication Adherence Scale (MMAS-8) prior to discharge and at one month after discharge. Data were analyzed using descriptive statistics and a paired sample t-test. RESULTS: The findings of SQLS demonstrate deterioration on psychosocial and motivation/energy domain (P<0.001) accompanied by improvement of symptom/side effect (P<0.05) after discharge. The scores of perceived stigma and actual stigma coping orientations (P<0.001) after discharge were found to be significantly higher than before discharge. Medication adherence was significantly reduced after discharge than before discharge (P<0.001). CONCLUSION: The results of this study provide implications for clinical practices, such as provision of psychosocial and educational rehabilitation programs for individuals who are in a stable mental status and plan to discharge; and to provide effective family education in order to improve family coping strategies and caring capabilities when patients return to the community. The findings provide important policy implications as well to facilitate individuals with schizophrenia to reintegrate into the community and benefit from a favorable QOL. PMID- 26804501 TI - Care Burden Level and Mental Health Condition of the Families of Individuals With Mental Disorders. AB - This study was conducted to assess burden of care levels and the mental health of the family members providing care to persons with mental disorders. The data were collected using the Information Form, Burden Assessment Scale (BAS) and General Health Questionnaire-12 (GHQ) (N=243). Of the caregivers included in this study, 67.49% were found to be at risk, and 47.3% of the caregivers were found to be at a high risk of developing mental disorders like depression and anxiety. A positive and statistically significant relation was identified between the BAS scores and GHQ scores of the caregivers (r=0.498; p=0.001). PMID- 26804502 TI - Internalized Stigma and Perceived Family Support in Acute Psychiatric In-Patient Units. AB - AIM: This descriptive study aims to identify the relationship between internalized stigma and perceived family support in patients hospitalized in an acute psychiatric unit. METHOD: The sample is composed of 224 patients treated in an acute inpatient psychiatric ward in Istanbul, Turkey. The data were collected using information obtained from the Internalized Stigma of Mental Illness Scale and Social Support from Family Scale. RESULTS: The mean age of the patients was 37+/-11.56years, and the mean duration of treatment was 6.27+/-5.81years. Most patients had been hospitalized three or more times. Of the total number of patients, 66.1% had been taken to the hospital by family members. We noted a statistically significant negative correlation between the total scores obtained from the perceived Social Support from Family Scale and the Internalized Stigma of Mental Illness Scale. CONCLUSION: The patients were observed to stigmatize themselves more when the perceived social support from their family had decreased. PMID- 26804503 TI - Pattern and Type of Aggressive Behavior in Patients with Severe Mental Illness as Perceived by the Caregivers and the Coping Strategies Used by Them in a Tertiary Care Hospital. AB - Aggressive behavior by patients with severe mental illness is a major problem needing intervention. This descriptive cross sectional study examined the perception and coping strategies of caregivers with a sample of 100 toward aggressive behavior by patients with severe mental illness in the outpatient and inpatient unit of the department of psychiatry in a tertiary care hospital. The data were collected by a semistructured interview using Revised Overt Aggression Scale-modified, Aggressive Behavior and Intervention Checklist, Ways of Coping Checklist-Hindi Adaptation and Impact of Patient Aggression on Carers Scale Adapted. The caregivers perceived aggression in varying extent from the patients. Majority used problem-focused coping to deal with aggressive behavior. Most of the caregivers perceived insisting to take medicines and talking about patient's illness as the triggers for aggressive behavior which was managed by talking to the patient calmly, lovingly and by leaving the patient alone. The findings strongly suggest aggressive behavior as a frequent problem faced by family members of patient with severe mental illness. Nursing interventions should focus on counseling and psycho education for empowering caregivers to utilize strategies to reduce occurrence of aggressive behavior from patient and ways to effectively cope with the situation. PMID- 26804504 TI - Structure of the Social Support Network of Patients with Severe and Persistent Psychiatric Disorders in Follow-Ups to Primary Health Care. AB - The objective of this study is to analyze the characteristics of social support networks of patients with psychiatric disorders at follow-up to primary care. This is a cross-sectional qualitative research study. Forty-five interviews were held with patients and their supporters. The results showed small and dense networks, with a strong emphasis on the bonds with formal supporters and a scant network of informal supporters. It is recommended to develop strategies to improve social support networks and use this as an outcome indicator related to social integration of these patients and to the quality of services involved with outpatient healthcare. PMID- 26804505 TI - Differences in Assessment of Suicidal Tendencies in Men and Women: A Pilot Study. AB - Suicidal behaviors in psychiatric patients are one of the main challenges in current clinical practice. The aim of this study was to investigate the gender differences in suicide risk for psychiatric patients in Poland and the influence of life satisfaction in different stages of life on suicidal tendencies. A descriptive-exploratory approach to inquiry was used for this study. Sixty patients aged 16-67 (45% males and 55% females) answered the demographic descriptive questionnaire, the Suicide Behaviors Questionnaire-Revised (SBQ-R) and the Cantril Self-Anchoring Striving Scale (CSASS). The results suggest that women turned out to show higher risk of suicidal behavior than men (p<0.001). Moreover, women displayed strong negative correlation between suicide risk and the anticipated life satisfaction in the future (rho=-0.542), while men displayed negative correlation between suicide risk and the pre-illness level of functioning (rho=-0.638). The findings suggest that different therapeutic approaches for each gender should be applied in suicide prevention process. PMID- 26804506 TI - Knowledge of Psychiatric Nurses About the Potentially Lethal Side-Effects of Clozapine. AB - Clozapine is an antipsychotic with superior efficacy in treatment refractory patients, and has unique anti-suicidal properties and a low propensity to cause extrapyramidal side-effects. Despite these advantages, clozapine utilization is low. This can in part be explained by a number of potentially lethal side effects of clozapine. Next to psychiatrists nurses play a crucial role in the long-term management of patients with schizophrenia. It is therefore important that nurses know, inform and monitor patients about the specific side-effects of clozapine. A recent study of psychiatrists published in 2011 has shown that there was a gap in the knowledge about side-effects of clozapine. The knowledge about side-effects of clozapine in nurses has never been studied. This cross-sectional study evaluated the knowledge base regarding the safety of clozapine, and its potential mediators, of psychiatric nurses in 3 psychiatric hospitals in Belgium with a specifically developed questionnaire based on the literature and expert opinion (3 clozapine experts). A total of 85 nurses completed the questionnaire. The mean total score was 6.1 of a potential maximum score of 18. Only 3 of the 18 multiple choice knowledge questions were answered correctly by more than 50% of nurses. Only 24.9% of participants passed the test (>50% correct answers). Nurses working on psychosis units were more likely to pass the test (xx.y% vs yy.z%, p=0.0124). There was a trend that nurses with a lower nursing diploma were more likely to fail the test (p=0.0561). Our study clearly identifies a large gap in the basic knowledge of psychiatric nurses about clozapine and its side-effects. Knowledge could be increased by more emphasis on the topic in nurse's training curricula as well as targeted onsite training. Only 23.5% of participants indicate that there was sufficient information in their basic nursing training. PMID- 26804507 TI - Depression and AIDS Preventive Self-efficacy Among Taiwanese Adolescents. AB - Effectively reducing adolescents' risky sexual behaviors has been an urgent need since the HIV/AIDS infections among young people has been acknowledged as a priority. Self-efficacy has been considered playing an essential role in behavioral changes, and depressed individuals may demonstrate lower self efficacy. The purpose of this cross-sectional study was to gain insights into self-reported depression among 16-18 years-old Taiwanese adolescents as well as to explore psychosocial predictors of AIDS preventive self-efficacy. A convenience sample of 734 adolescents from southern Taiwan was recruited, and several reliable and valid questionnaires were used to collect data. Descriptive statistics, odds ratio, independent t-test, and hierarchical multiple regression analyses were utilized to analyze data. Results showed that the differences in self-reported depression and in the AIDS preventive self-efficacy varied by gender, substance use, and having sexual experience. Furthermore, depression was a significant predictor of AIDS preventive self-efficacy while controlling the covariates. This study suggests that gender and mental health status such as depression may play significant roles in AIDS preventive self-efficacy. Nurses and health care providers should take the influence of mental health into consideration when designing AIDS preventive interventions for male and female Taiwanese adolescents. The provided information may also enhance psychiatric nurses' capability to provide care and to enhance the prevention of HIV infection for adolescents. PMID- 26804508 TI - Parenting in the Wake of Abuse: Exploring the Mediating Role of PTSD Symptoms on the Relationship Between Parenting and Child Functioning. AB - BACKGROUND: Children whose mothers report partner violence and symptoms of posttraumatic stress disorder (PTSD) are at risk for behavior dysfunctions. AIM: To examine the mediating effects of maternal PTSD symptoms on the relationship of parenting behaviors to child internalizing and externalizing behavior dysfunctions. FINDINGS: Maternal PTSD symptoms have a partial mediating effect on the relationship between inconsistent discipline and child internalizing and externalizing behaviors. Maternal PTSD symptoms have a fully mediating effect on the relationship between poor supervision and child internalizing behaviors. CONCLUSIONS: There is a need to identify women who report partner violence and are at high risk for PTSD and intervene early to prevent problematic parenting and resulting child behavior problems. PMID- 26804509 TI - Factors Associated with Post-Traumatic Symptoms in Mothers of Preterm Infants. AB - OBJECTIVES: Symptoms of post-traumatic distress in mothers of preterm infants have been a subject of mental health research. The aim of this study was to assess the prevalence of and risk factors associated with such symptoms in mothers of preterm infants in Taiwan. METHODS: This was a cross-sectional study performed between January 1, 2010 and June 30, 2011. One hundred and two mothers of preterm infants born at less than 37 weeks gestation and with a subsequent neonatal intensive care unit (NICU) stay between 2005 and 2009 were recruited. Participants completed a demographic questionnaire, the Impact of Event Scale Revised (IES-R), the Center for Epidemiologic Studies Depression Scale (CES-D) and the neuroticism subscale of the Maudsley Personality Inventory (MPI). The preterm infants' data were taken from medical records. RESULTS: The prevalence of symptoms of distress was 25.5% (26/102) in the participants. These symptoms were associated with previous miscarriages, preterm premature rupture of membranes, neurotic personality and depression. CONCLUSIONS: The experience of preterm birth and NICU hospitalization can be traumatic to mothers. Early support for mothers during the preterm infants' NICU stay and transition to home care are recommended. PMID- 26804510 TI - Integrating Evidence-Based Community-Care Services to Improve Schizophrenia Outcomes: A Preliminary Trial. AB - This aim of this preliminary experimental study was to integrate effective evidence-based community-care services that are subjected to heavy caseloads, and to then examine the effects on individuals with schizophrenia. Using a cluster sampling method, four homecare nurses were randomly assigned to either the experimental group or the comparison group. The nurses in the experimental group applied the following six identified effective elements: (1) established an alliance with their patients; (2) assessed patient-care needs; (3) considered both medical and social-care practices; (4) addressed patients' self-management of medication and their daily tasks; (5) provided crisis intervention; and (6) coordinated resources. The patients comprised 85 individuals with schizophrenia. In the experimental group, psychiatric homecare nurses were randomly assigned to implement integrated, evidence-based community-care services during a six-month follow-up period. Patients in the comparison group continued to receive their customary community care. In the experimental group, patient satisfaction scores, medication attitudes, and general functioning levels were significantly higher than in the comparison group. These preliminary findings indicate a potentially effective model for community care in areas where intensive case management cannot be provided. PMID- 26804511 TI - Impact of Perceived Stress, Anxiety-Depression and Social Support on Coping Strategies of Parents Having A Child With Gilles de la Tourette Syndrome. AB - PURPOSE: Previous reports have indicated that raising a child with Gilles de la Tourette syndrome (GTS) could be considered a stressful experience. Thus our study aimed to assess the impact of perceived stress (i.e. parental cognitive perception of their child's disorder) and social support (number of people surrounding the subject providing support) on coping strategies-defined as processes of restoring balance between excessive demands and inadequate resources of parents having a child with GTS. METHODS: Twenty-eight parents of 21 patients with GTS (aged 6 to 16years) completed questionnaires on perceived stress (ALE Scale), social support (SSQ6), coping strategies (WCC-R) and anxiety-depression (HAD). RESULTS: Principal component analysis showed a negative correlation between social support on one side and perceived stress and anxiety/depression on the other. Problem- and emotion-focused coping both correlated with social support, all of them being independent from perceived stress and anxiety/depression. Hierarchical ascendant classification showed three clusters of individuals in our parents' groups: i) those having high scores in perceived stress and anxiety-depression; ii) those having high scores in social support associated with low scores in perceived stress; iii) parents having lower than average scores on both problem- and emotion- focused coping and social support. CONCLUSION: Our results reinforce the need for developing training programs for parents with GTS children to better understand and tolerate the disorder to decrease their stress. PMID- 26804512 TI - Effectiveness of Telephone-Delivered Interventions Following Suicide Attempts: A Systematic Review. AB - AIM: To evaluate efficacy of telephone-delivered interventions following suicide attempts. METHODS: Systematic review, meta-analysis, and narrative synthesis. RESULTS: Five papers evaluating telephone interventions were included. Three studies provided suicide attempters with telephone contact intervention, and two studies provided deliberate self-harm patients with crisis cards to help after discharge. Meta-analyses showed that telephone contact intervention did not significantly reduce further suicide attempts and completed suicides, and the crisis card did not significantly reduce further deliberate self-harm. CONCLUSION: Telephone-delivered interventions have been suggested as an alternative to face-to-face psychotherapy, but their effectiveness in reducing the recurrence of suicide attempts is not supported. PMID- 26804513 TI - Post-Seclusion and/or Restraint Review in Psychiatry: A Scoping Review. AB - CONTEXT: It has been suggested that after an incident in which a patient has been placed in seclusion or in restraints, an intervention should be conducted after the event to ensure continuity of care and prevent recurrences. Several terms are used, and various models have been suggested for post-seclusion and/or restraint review; however, the intervention has never been precisely defined. OBJECTIVE: This article presents a scoping review on post-seclusion and/or restraint review in psychiatry to examine existing models and the theoretical foundations on which they rely. METHOD: A scoping review of academic articles (CINAHL and Medline database) yielded 28 articles. RESULTS: Post-seclusion and/or restraint review has its origins in the concepts of debriefing in psychology and reflective practice in nursing. We propose a typology in terms of the intervention target, including the patient, the health care providers, or both. IMPLICATIONS: The analysis found that the review ought to involve both the patient and the care providers using an approach that fosters reflexivity among all those involved in order to change the practice of seclusion in psychiatric settings. ACCESSIBLE SUMMARY: * Established literature documented widely that seclusion and restraint has adverse physical and psychological consequences for patient and for health care providers. * Post-seclusion and/or restraint review is promoted in most guidelines, but there is no scoping or systematic review yet on the subject. * The origins of post-seclusion and/or restraint review are in the concepts of debriefing in psychology and reflective practice in nursing. * We propose that post-seclusion and/or restraint review should focus on both patients and health care providers.* Systematic post-seclusion and/or restraint review should be performed after each event, and its effects on patients and on mental health professionals should be rigorously assessed. PMID- 26804544 TI - Biomarkers in bladder cancer: A metabolomic approach using in vitro and ex vivo model systems. AB - Metabolomics has recently proved to be useful in the area of biomarker discovery for cancers in which early diagnostic and prognostic biomarkers are urgently needed, as is the case of bladder cancer (BC). This article presents a comprehensive review of the literature on the metabolomic studies on BC, highlighting metabolic pathways perturbed in this disease and the altered metabolites as potential biomarkers for BC detection. Current disease model systems used in the study of BC metabolome include in vitro-cultured cancer cells, ex vivo neoplastic bladder tissues and biological fluids, mainly urine but also blood serum/plasma, from BC patients. The major advantages and drawbacks of each model system are discussed. Based on available data, it seems that BC metabolic signature is mainly characterized by alterations in metabolites related to energy metabolic pathways, particularly glycolysis, amino acid and fatty acid metabolism, known to be crucial for cell proliferation, as well as glutathione metabolism, known to be determinant in maintaining cellular redox balance. In addition, purine and pyrimidine metabolism as well as carnitine species were found to be altered in BC. Finally, it is emphasized that, despite the progress made in respect to novel biomarkers for BC diagnosis, there are still some challenges and limitations that should be addressed in future metabolomic studies to ensure their translatability to clinical practice. PMID- 26804545 TI - Use of Raman spectroscopy to identify active spermatogenesis and Sertoli-cell only tubules in mice. AB - Microdissection testicular sperm extraction (micro-TESE) has become the first line therapy to harvest spermatozoa for men with nonobstructive azoospermia. However, the pitfall is that the selection of seminiferous tubules depends on subjective assessment of the colour and size of tubules, which cannot guarantee successful retrieval of spermatozoa. The aim of this study was to determine whether Raman spectroscopy (RS) could distinguish tubules with spermatogenesis from Sertoli-cell-only (SCO) tubules, and potentially serve as a useful tool to improve sperm retrieval rates. Fourteen male adult mice were divided into two groups: SCO group received a single intraperitoneal injection of busulfan (40 mg per kg body weight), and the control group received a placebo dose of 0.9% saline solution. Mice were sacrificed after 4 weeks, and the testicular tissue was assessed by RS and then confirmed with histopathology. The results indicated that tubules with spermatogenesis had intensified Raman peaks at 748, 1124, 1309, 1446 and 1658 cm-1 compared to SCO tubules, except a decreased peak at 1582 cm-1 . RS was able to distinguish the two groups with a sensitivity of 91.2% and specificity of 82.9%. In conclusion, RS may serve as a useful diagnostic tool prior to sperm retrieval. PMID- 26804546 TI - Mapping multidimensional electronic structure and ultrafast dynamics with single element detection and compressive sensing. AB - Compressive sensing allows signals to be efficiently captured by exploiting their inherent sparsity. Here we implement sparse sampling to capture the electronic structure and ultrafast dynamics of molecular systems using phase-resolved 2D coherent spectroscopy. Until now, 2D spectroscopy has been hampered by its reliance on array detectors that operate in limited spectral regions. Combining spatial encoding of the nonlinear optical response and rapid signal modulation allows retrieval of state-resolved correlation maps in a photosynthetic protein and carbocyanine dye. We report complete Hadamard reconstruction of the signals and compression factors as high as 10, in good agreement with array-detected spectra. Single-point array reconstruction by spatial encoding (SPARSE) Spectroscopy reduces acquisition times by about an order of magnitude, with further speed improvements enabled by fast scanning of a digital micromirror device. We envision unprecedented applications for coherent spectroscopy using frequency combs and super-continua in diverse spectral regions. PMID- 26804548 TI - A comparison of trunk biomechanics, musculoskeletal discomfort and productivity during simulated sit-stand office work. AB - Sedentary office work has been shown to cause low back discomfort and potentially cause injury. Prolonged standing work has been shown to cause discomfort. The implementation of a sit-stand paradigm is hypothesised to mitigate discomfort and prevent injury induced by prolonged exposure to each posture in isolation. This study explored the potential of sit-stand to reduce discomfort and prevent injury, without adversely affecting productivity. Twenty-four participants performed simulated office work in three different conditions: sitting, standing and sit-stand. Variables measured included: perceived discomfort, L4-L5 joint loading and typing/mousing productivity. Working in a sit-stand paradigm was found to have the potential to reduce discomfort when compared to working in a sitting or standing only configuration. Sit-stand was found to be associated with reduced lumbar flexion during sitting compared to sitting only. Increasing lumbar flexion during prolonged sitting is a known injury mechanism. Therefore, sit stand exhibited a potentially beneficial response of reduced lumbar flexion that could have the potential to prevent injury. Sit-stand had no significant effect on productivity. Practitioner Summary: This study has contributed foundational elements to guide usage recommendations for sit-stand workstations. The sit-stand paradigm can reduce discomfort; however, working in a sit-stand ratio of 15:5 min may not be the most effective ratio. More frequent posture switches may be necessary to realise the full benefit of sit-stand. PMID- 26804547 TI - Conducted dilatation to ATP and K+ in rat skeletal muscle arterioles. AB - AIM: During exercise in humans, circulating levels of ATP and K+ increase at a time when blood flow increases to satisfy metabolic demand. Both molecules can activate arteriolar K+ channels to stimulate vasodilatation; here, it is established whether conducted dilatation is observed in a skeletal muscle bed. METHODS: Isolated and cannulated rat cremaster arterioles were used to assess both local and conducted responses. Agents were either added to the bath, focally pulse-ejected to the downstream end of arterioles, or in triple-cannulated arterioles, luminally perfused into the downstream branches to assess both local and conducted responses. RESULTS: The endothelium-dependent agonist ACh and the KATP channel opener levcromakalim each stimulated both local and conducted vasodilatation. Focal, bolus delivery of ATP (10 MUm) or KCl (33 mm) to the outside of arterioles stimulated a biphasic vasomotor response: rapid vasoconstriction followed by dilatation as each washed away. At lower concentrations of KCl (19 mm), constriction was avoided, and instead, Ba2+ sensitive local dilatation and conducted dilatation were both observed. Luminal perfusion of ATP avoided constriction and activated P2Y1 receptors stimulating vasodilatation secondary to opening of KCa channels. In triple-cannulated arterioles, either ATP (10 MUm) or K+ (15 mm) luminally perfused into daughter branches of a bifurcation stimulated local dilatation which conducted into the parent arteriole. CONCLUSION: The recognized physiological autocrine and paracrine mediators ATP and K+ each act to evoke both local and conducted vasodilatation in rat cremaster arterioles. Therefore, in situations when circulating levels are raised, such as during exercise, these agents can act as important regulators of blood flow. PMID- 26804549 TI - Upregulation of the double-stranded RNA binding protein DGCR8 in invasive ductal breast carcinoma. AB - High-throughput experimental studies have indicated that the miRNAome is globally downregulated in various types of malignancy, and dysregulation of miRNAs processing component(s) is one possible mechanism for this phenomenon. Despite the progression in identifying cellular functions of Digeorge Syndrome Critical Region 8 (DGCR8) in miRNAs biogenesis, the role of altered expression of DGCR8 in the pathogenesis of invasive ductal breast carcinoma (IDC) has not yet been fully investigated. The objective of the present study was to evaluate DGCR8 mRNA expression in seventy fresh invasive ductal breast carcinomas and matched adjacent non-neoplastic tissues using quantitative real-time PCR and to assess the value of clinicopathological parameters on its expression. Our findings revealed that DGCR8 mRNA expression is upregulated in more than two-thirds of the cancerous specimens (68.66%) when compared to adjacent non-neoplastic tissue. This difference is statistically significant (P<0.05). We found that DGCR8 mRNA levels were increased in the high-grade and metastatic compared with those of both low-grade and non-metastatic. We demonstrated that there is not significant correlation between DGCR8 mRNA expression levels and clinicopathological parameters. In conclusion, our study suggested that upregulation of DGCR8 may be involved in tumorigenesis and aggressiveness of IDC and may serve as future therapeutic target. PMID- 26804550 TI - Molecular mechanisms associated with breast cancer based on integrated gene expression profiling by bioinformatics analysis. AB - In this study, we aimed to gain more insights into the underlying molecular mechanisms responsible for breast cancer (BC) progression. Three gene expression profiles of human BC were integrated and used to screen the differentially expressed genes (DEGs) between healthy breast samples and BC samples. Protein protein interaction (PPI) network of DEGs was constructed by mapping DEGs into the Search Tool for the Retrieval of Interacting Genes (STRING) database; then the subnetworks of PPI were constructed with plug-in, MCODE and DEGs in Subnetwork 1 were analysed based on Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway database ( http://www.genome.jp/kegg /). In addition, co expression network of DEGs was established using the Cytoscape. Totalally 931 DEGs were selected, including 340 up-regulated genes and 591 down-regulated genes. KEGG pathway analysis for DEGs in Subnetwork 1 showed that the pathogenesis of BC was associated with cell cycle, oocyte meiosis, progesterone mediated oocyte maturation and p53 signalling pathways. Meanwhile, the most significant-related DEGs were found by co-expression network analysis of DEGs. In conclusion, CCNG1 might be involved in the progression of BC via inhibiting cell proliferation, and ADAMTS1 might play a crucial role in BC development through the regulation of angiogenesis. PMID- 26804551 TI - Simple Peptide-Tuned Self-Assembly of Photosensitizers towards Anticancer Photodynamic Therapy. AB - Peptide-tuned self-assembly of functional components offers a strategy towards improved properties and unique functions of materials, but the requirement of many different functions and a lack of understanding of complex structures present a high barrier for applications. Herein, we report a photosensitive drug delivery system for photodynamic therapy (PDT) by a simple dipeptide- or amphiphilic amino-acid-tuned self-assembly of photosensitizers (PSs). The assembled nanodrugs exhibit multiple favorable therapeutic features, including tunable size, high loading efficiency, and on-demand drug release responding to pH, surfactant, and enzyme stimuli, as well as preferable cellular uptake and biodistribution. These features result in greatly enhanced PDT efficacy in vitro and in vivo, leading to almost complete tumor eradication in mice receiving a single drug dose and a single exposure to light. PMID- 26804553 TI - Robust DNA Methylation in the Clonal Raider Ant Brain. AB - Social insects are promising model systems for epigenetics due to their immense morphological and behavioral plasticity. Reports that DNA methylation differs between the queen and worker castes in social insects [1-4] have implied a role for DNA methylation in regulating division of labor. To better understand the function of DNA methylation in social insects, we performed whole-genome bisulfite sequencing on brains of the clonal raider ant Cerapachys biroi, whose colonies alternate between reproductive (queen-like) and brood care (worker-like) phases [5]. Many cytosines were methylated in all replicates (on average 29.5% of the methylated cytosines in a given replicate), indicating that a large proportion of the C. biroi brain methylome is robust. Robust DNA methylation occurred preferentially in exonic CpGs of highly and stably expressed genes involved in core functions. Our analyses did not detect any differences in DNA methylation between the queen-like and worker-like phases, suggesting that DNA methylation is not associated with changes in reproduction and behavior in C. biroi. Finally, many cytosines were methylated in one sample only, due to either biological or experimental variation. By applying the statistical methods used in previous studies [1-4, 6] to our data, we show that such sample-specific DNA methylation may underlie the previous findings of queen- and worker-specific methylation. We argue that there is currently no evidence that genome-wide variation in DNA methylation is associated with the queen and worker castes in social insects, and we call for a more careful interpretation of the available data. PMID- 26804554 TI - Local Slow Waves in Superficial Layers of Primary Cortical Areas during REM Sleep. AB - Sleep is traditionally constituted of two global behavioral states, non-rapid eye movement (NREM) and rapid eye movement (REM), characterized by quiescence and reduced responsiveness to sensory stimuli [1]. NREM sleep is distinguished by slow waves and spindles throughout the cerebral cortex and REM sleep by an "activated," low-voltage fast electroencephalogram (EEG) paradoxically similar to that of wake, accompanied by rapid eye movements and muscle atonia. However, recent evidence has shown that cortical activity patterns during wake and NREM sleep are not as global as previously thought. Local slow waves can appear in various cortical regions in both awake humans [2] and rodents [3-5]. Intracranial recordings in humans [6] and rodents [4, 7] have shown that NREM sleep slow waves most often involve only a subset of brain regions that varies from wave to wave rather than occurring near synchronously across all cortical areas. Moreover, some cortical areas can transiently "wake up" [8] in an otherwise sleeping brain. Yet until now, cortical activity during REM sleep was thought to be homogenously wake-like. We show here, using local laminar recordings in freely moving mice, that slow waves occur regularly during REM sleep, but only in primary sensory and motor areas and mostly in layer 4, the main target of relay thalamic inputs, and layer 3. This finding may help explain why, during REM sleep, we remain disconnected from the environment even though the bulk of the cortex shows wake like, paradoxical activation. PMID- 26804555 TI - Experimental Evidence of an Eco-evolutionary Feedback during Adaptive Divergence. AB - Differences in how organisms modify their environment can evolve rapidly and might influence adaptive population divergence. In a common garden experiment in aquatic mesocosms, we found that adult stickleback from a recently diverged pair of lake and stream populations had contrasting effects on ecosystem metrics. These modifications were caused by both genetic and plastic differences between populations and were sometimes comparable in magnitude to those caused by the presence/absence of stickleback. Lake and stream fish differentially affected the biomass of zooplankton and phytoplankton, the concentration of phosphorus, and the abundance of several prey (e.g., copepods) and non-prey (e.g., cyanobacteria) species. The adult-mediated effects on mesocosm ecosystems influenced the survival and growth of a subsequent generation of juvenile stickleback reared in the same mesocosms. The prior presence of adults decreased the overall growth rate of juveniles, and the prior presence of stream adults lowered overall juvenile survival. Among the survivors, lake juveniles grew faster than co occurring stream juveniles, except in mesocosm ecosystems previously modified by adult lake fish that were reared on plankton. Overall, our results provide evidence for reciprocal interactions between ecosystem dynamics and evolutionary change (i.e., eco-evolutionary feedbacks) in the early stages of adaptive population divergence. PMID- 26804556 TI - Ecological Impacts of Reverse Speciation in Threespine Stickleback. AB - Young species are highly prone to extinction via increased gene flow after human caused environmental changes. This mechanism of biodiversity loss, often termed reverse speciation or introgressive extinction, is of exceptional interest because the parent species are typically highly differentiated ecologically. Reverse speciation events are potentially powerful case studies for the role of evolution in driving ecological changes, as the phenotypic shifts associated with introgressive extinction can be large and they occur over particularly short timescales. Furthermore, reverse speciation can lead to novel phenotypes, which may in turn produce novel ecological effects. Here we investigate the ecological shift associated with reverse speciation in threespine stickleback fish using a field study and a replicated experiment. We find that an instance of introgressive extinction had cascading ecological consequences that altered the abundance of both aquatic prey and the pupating aquatic insects that emerged into the terrestrial ecosystem. The community and ecosystem impacts of reverse speciation were novel, and yet they were also predictable based on ecological and morphological considerations. The study suggests that knowledge about the community ecology and changes in functional morphology of a dominant species may lead to some predictive power for the ecological effects of evolutionary change. Moreover, the rapid nature and resultant ecological impacts associated with reverse speciation demonstrates the interplay between biodiversity, evolutionary change, and ecosystem function. PMID- 26804557 TI - The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake. AB - Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na(+)-rich animal and nutrition for the plant. PMID- 26804558 TI - Divergence and Functional Degradation of a Sex Chromosome-like Supergene. AB - A major challenge in biology is to understand the genetic basis of adaptation. One compelling idea is that groups of tightly linked genes (i.e., "supergenes" [1, 2]) facilitate adaptation in suites of traits that determine fitness. Despite their likely importance, little is known about how alternate supergene alleles arise and become differentiated, nor their ultimate fate within species. Herein we address these questions by investigating the evolutionary history of a supergene in white-throated sparrows, Zonotrichia albicollis. This species comprises two morphs, tan and white, that differ in pigmentation and components of social behavior [3-5]. Morph is determined by alternative alleles at a balanced >100-Mb inversion-based supergene, providing a unique system for studying gene-behavior relationships. Using over two decades of field data, we document near-perfect disassortative mating among morphs, as well as the fitness consequences of rare assortative mating. We use de novo whole-genome sequencing coupled with population- and phylogenomic data to show that alternate supergene alleles are highly divergent at over 1,000 genes and that these alleles originated prior to the split of Z. albicollis from its sister species and may be polymorphic in Z. albicollis due to a past hybridization event. We provide evidence that the "white" allele may be degrading, similar to neo-Y/W sex chromosomes. We further show that the "tan" allele has surprisingly low levels of genetic diversity yet does not show several canonical signatures of recurrent positive selection. We discuss these results in the context of the origin, molecular evolution, and possible fate of this remarkable polymorphism. PMID- 26804559 TI - Bacterial Autoimmunity Due to a Restriction-Modification System. AB - Restriction-modification (RM) systems represent a minimal and ubiquitous biological system of self/non-self discrimination in prokaryotes [1], which protects hosts from exogenous DNA [2]. The mechanism is based on the balance between methyltransferase (M) and cognate restriction endonuclease (R). M tags endogenous DNA as self by methylating short specific DNA sequences called restriction sites, whereas R recognizes unmethylated restriction sites as non self and introduces a double-stranded DNA break [3]. Restriction sites are significantly underrepresented in prokaryotic genomes [4-7], suggesting that the discrimination mechanism is imperfect and occasionally leads to autoimmunity due to self-DNA cleavage (self-restriction) [8]. Furthermore, RM systems can promote DNA recombination [9] and contribute to genetic variation in microbial populations, thus facilitating adaptive evolution [10]. However, cleavage of self DNA by RM systems as elements shaping prokaryotic genomes has not been directly detected, and its cause, frequency, and outcome are unknown. We quantify self restriction caused by two RM systems of Escherichia coli and find that, in agreement with levels of restriction site avoidance, EcoRI, but not EcoRV, cleaves self-DNA at a measurable rate. Self-restriction is a stochastic process, which temporarily induces the SOS response, and is followed by DNA repair, maintaining cell viability. We find that RM systems with higher restriction efficiency against bacteriophage infections exhibit a higher rate of self restriction, and that this rate can be further increased by stochastic imbalance between R and M. Our results identify molecular noise in RM systems as a factor shaping prokaryotic genomes. PMID- 26804560 TI - Abdominal Pocket Method as a Salvage Procedure for Vascular Insufficiency After Distal Digital Replantation. AB - PURPOSE: To assess the utility of abdominal pocketing of a deepithelialized reattached digit to allow for neovascularization as a salvage procedure for circulatory insufficiency after digital replantation. We performed this method in Tamai zone II cases in which microsurgical vascular anastomosis was expected to be difficult based on the findings at the initial operation. MATERIALS AND METHODS: From 2008 to 2014, 5 injured digits from 5 patients (mean age, 34 years; range: 25-54 years) underwent the abdominal pocket method as a salvage procedure for postoperative circulatory insufficiency. We evaluated the survival incidence, the timing between operations, and the duration of the second operation. During this study period, 7 amputated digits from 7 patients underwent vascular reanastomosis. We also evaluated the survival incidence for these cases. RESULTS: Four out of 5 replanted digital tips survived. The mean time between the initial operation and the onset of vascular problems was 82 hours, and the mean duration of the second operation was 48 minutes. The survival incidence for reanastomosed cases was 6 out of 7. CONCLUSIONS: The abdominal pocket method is useful for treating circulatory insufficiency after digital replantation in Tamai zone II cases in which microsurgical vascular reanastomosis was expected to be difficult based on the findings at the initial operation. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 26804561 TI - Efficacy of two noninvasive weaning strategies in intubated patients with chronic obstructive pulmonary disease: A meta-analysis and indirect treatment comparison. AB - The purpose of our indirect comparison was to explore the optimal switching time to noninvasive ventilation for further weaning in patients with chronic obstructive pulmonary disease (COPD) undergoing invasive mechanical ventilation. A comprehensive literature search was performed to identify randomized controlled trials comparing noninvasive weaning at spontaneous breathing trial (SBT) failure after meeting simple weaning criteria or at the pulmonary infection control window (PIC window) with conventional invasive weaning in COPD patients. Using conventional invasive weaning as a bridge, we indirectly compared the two noninvasive weaning strategies using the Bucher approach. Noninvasive weaning at SBT failure after meeting simple weaning criteria was associated with an extended duration of endotracheal mechanical ventilation (standardized mean difference 1.90, 95% CI 1.27-2.53, P < 0.001) compared with noninvasive weaning at the PIC window. No significant differences in mortality or the rate of ventilator associated pneumonia were observed. Our study suggests that the PIC window may be a promising switching time for noninvasive weaning in COPD patients. PMID- 26804564 TI - Small molecule MALDI MS imaging: Current technologies and future challenges. AB - Imaging of specific small molecules is particularly challenging using conventional optical microscopy techniques. This has led to the development of alternative imaging modalities, including mass spectrometry (MS)-based methods. This review aims to provide an overview of the technologies, methods and future directions of laser-based mass spectrometry imaging (MSI) of small molecules. In particular it will focus on matrix-assisted laser desorption/ionization (MALDI) as the ion source, although other laser mass spectrometry methods will also be discussed to provide context, both historical and current. Small molecule MALDI MSI has been performed on a wide variety of instrument platforms: these are reviewed, as are the laser systems that are commonly used in this technique. Instrumentation and methodology cross over in the areas of achieving optimal spatial resolution, a key parameter in obtaining meaningful data. Also discussed is sample preparation, which is pivotal in maintaining sample integrity, providing a true reflection of the distribution of analytes, spatial resolution and sensitivity. Like all developing analytical techniques there are challenges to be overcome. Two of these are dealing with sample complexity and obtaining quantitative information from an imaging experiment. Both of these topics are addressed. Finally, novel experiments including non-MALDI laser ionization techniques are highlighted and a future perspective on the role of MALDI MSI in the small molecule arena is provided. PMID- 26804563 TI - Antibody-based affinity cryo-EM grid. AB - The Affinity Grid technique combines sample purification and cryo-Electron Microscopy (cryo-EM) grid preparation into a single step. Several types of affinity surfaces, including functionalized lipids monolayers, streptavidin 2D crystals, and covalently functionalized carbon surfaces have been reported. More recently, we presented a new affinity cryo-EM approach, cryo-SPIEM, which applies the traditional Solid Phase Immune Electron Microscopy (SPIEM) technique to cryo EM. This approach significantly simplifies the preparation of affinity grids and directly works with native macromolecular complexes without need of target modifications. With wide availability of high affinity and high specificity antibodies, the antibody-based affinity grid would enable cryo-EM studies of the native samples directly from cell cultures, targets of low abundance, and unstable or short-lived intermediate states. PMID- 26804565 TI - MBT-ASTRA: A suitable tool for fast antibiotic susceptibility testing? AB - The increasing resistance to antibiotics is an urgent health care problem. Detection of resistant microorganisms is the pre-requisite for initiating an adequate therapy and implementing respective hygiene measures. Depending on the species and the method employed for analysis, the time to result of antibiotic resistance testing ranges between five and 24h. As MALDI-TOF MS has become an established tool for the fast species identification in microbiological laboratories a time gap between the results of species identification and the information about antibiotic susceptibility arises. Here, we present a semi quantitative MALDI-TOF MS-based approach for the detection of resistance in different species against different antibiotics. PMID- 26804562 TI - Advances in the molecular dynamics flexible fitting method for cryo-EM modeling. AB - Molecular Dynamics Flexible Fitting (MDFF) is an established technique for fitting all-atom structures of molecules into corresponding cryo-electron microscopy (cryo-EM) densities. The practical application of MDFF is simple but requires a user to be aware of and take measures against a variety of possible challenges presented by each individual case. Some of these challenges arise from the complexity of a molecular structure or the limited quality of available structural models and densities to be interpreted, while others stem from the intricacies of MDFF itself. The current article serves as an overview of the strategies that have been developed since MDFF's inception to overcome common challenges and successfully perform MDFF simulations. PMID- 26804566 TI - 21-hydroxylase deficiency-induced congenital adrenal hyperplasia in 230 Chinese patients: Genotype-phenotype correlation and identification of nine novel mutations. AB - Steroid 21-hydroxylase deficiency (21-OHD) caused by the CYP21A2 gene mutations accounts for more than 90% of congenital adrenal hyperplasia (CAH) cases. In this study, molecular defects of 230 patients with 21-OHD were investigated. Point mutations of CYP21A2 gene were analyzed by Sanger sequencing, and large gene deletions were detected by multiplex ligation-dependent probe amplification (MLPA). Nine micro-conversions and 18 spontaneous mutations accounted for 74.6% of alleles, while large gene deletions and large gene conversions accounted for 25.4% of alleles. The most frequent micro-conversion was c.292-13A/C>G (I2G) (35%), followed by p.I173N (14.3%), p.R357W (5.9%) and p.Q319* (4.6%). Nine novel mutations were identified in these patients, which were predicted to hamper the 21-hydroxylase protein function in varying degrees. Genotype and phenotype correlated well in 89.6% of our patients, but disparity in phenotypic appearance also appeared in a small portion of the patients. 16.1% of the patients carried homozygous genotypes while 83.9% of patients carried compound heterozygous mutations. We concluded that the frequency of CYP21A2 mutations in our study was slightly different from those reported for other ethnic groups. Micro-conversions were the main category of the mutation spectrum, while large deletions and large gene conversions could also cause 21-OHD. A large portion of different types of the compound heterozygous genotypes may partially contribute to the discordance in genotype-phenotype comparison. This study expanded the CYP21A2 mutation spectrum of Chinese patients and could be helpful in prenatal diagnosis and genetic counseling for 21-OHD patients. PMID- 26804567 TI - Strategies for phrenic nerve preservation during ablation of inappropriate sinus tachycardia. AB - BACKGROUND: Radiofrequency (RF) ablation can alleviate drug-refractory inappropriate sinus tachycardia (IST). However, phrenic nerve (PN) injury and other complications limit its use. OBJECTIVE: The purpose of this study was to characterize the maneuvers used to avoid PN injury and the long-term clinical outcomes. METHODS: The study consisted of a retrospective analysis of consecutive patients who underwent ablation for IST. RESULTS: RF ablation was performed on 13 consecutive female patients with drug-refractory IST. Eleven patients exhibited PN capture at desired ablation sites. In 1 patient, PN capture was not continuous throughout the respiratory cycle and ventilation holding sufficed to avoid PN injury. In 10 patients, pericardial access (PA) and balloon insertion was required. Initially (n = 4) a posterior PA was used, which was replaced by an anterior PA in the subsequent 6 cases. PA to optimal balloon positioning time was significantly lower in anterior vs posterior PA (16.3 +/- 6 minutes vs 58 +/- 21.3 minutes, P = .01), as was fluoroscopy time (15.66 +/- 16.72 min vs 35.9 +/- 1.8 min, P = .03). RF ablation successfully reduced sinus rate to <90 bpm in 13 of 13 patients. Procedure times and total RF times were not significantly different in anterior vs posterior PA. Major complications occurred in 2 patients, including unremitting pericardial bleeding requiring open-chested repair in 1 patient and sinus pauses mandating pacemaker implantation in the other patient. Long-term symptom control after follow-up of 811 +/- 42 days was successful in 84.6%. CONCLUSION: Ventilation holding and/or pericardial balloon insertion are frequently warranted in IST ablation. Anterior PA appears to facilitate the procedure over posterior PA. PMID- 26804568 TI - Catheter ablation for atrioventricular nodal reentrant tachycardia in patients with congenital heart disease. AB - BACKGROUND: Variability in atrioventricular (AV) node location in congenital heart disease (CHD) can make catheter ablation for atrioventricular nodal reentrant tachycardia (AVNRT) challenging. OBJECTIVE: The purpose of this study was to describe institutional technique and outcomes for slow pathway modification in a cohort with CHD. METHODS: The study consisted of a retrospective review of CHD patients who underwent study from 2001 to 2013 with a diagnosis of AVNRT. Outcomes for slow pathway modification were recorded. In cases in which ablation was deferred, the reasons for this choice were examined. RESULTS: Forty-nine patients (median age 19 years) were included. CHD anatomy involved d-transposition of the great arteries (n = 6), "congenitally corrected" transposition of the great arteries (n = 4), Ebstein anomaly (n = 4), tetralogy of Fallot (n = 5), venous anomalies (n = 8), single ventricle (n = 16), and miscellaneous (n = 6). Ablation was attempted in 39 patients, using radiofrequency energy in 24, cryoablation in 8, and both in 7. Acute success rate was 92% (36/39). One patient had first-degree block in response to cryoablation, but no other complications occurred. At median follow-up 32 months, 1 patient had AVNRT recurrence. Most of the 10 patients in whom ablation was deferred had single-ventricle anatomy with uncertain AV node location. CONCLUSION: Ablation for AVNRT in CHD can be accomplished successfully with attention to underlying anatomy and prior surgery. Patients with single ventricle are a difficult subgroup, and a pharmacologic approach may be indicated in some cases if node localization is ambiguous. PMID- 26804569 TI - Structures of the DfsB Protein Family Suggest a Cationic, Helical Sibling Lethal Factor Peptide. AB - Bacteria have developed a variety of mechanisms for surviving harsh environmental conditions, nutrient stress and overpopulation. Paenibacillus dendritiformis produces a lethal protein (Slf) that is able to induce cell death in neighbouring colonies and a phenotypic switch in more distant ones. Slf is derived from the secreted precursor protein, DfsB, after proteolytic processing. Here, we present new crystal structures of DfsB homologues from a variety of bacterial species and a surprising version present in the yeast Saccharomyces cerevisiae. Adopting a four-helix bundle decorated with a further three short helices within intervening loops, DfsB belongs to a non-enzymatic class of the DinB fold. The structure suggests that the biologically active Slf fragment may possess a C-terminal helix rich in basic and aromatic residues that suggest a functional mechanism akin to that for cationic antimicrobial peptides. PMID- 26804570 TI - The Bacillus subtilis and Bacillus halodurans Aspartyl-tRNA Synthetases Retain Recognition of tRNA(Asn). AB - Synthesis of asparaginyl-tRNA (Asn-tRNA(Asn)) in bacteria can be formed either by directly ligating Asn to tRNA(Asn) using an asparaginyl-tRNA synthetase (AsnRS) or by synthesizing Asn on the tRNA. In the latter two-step indirect pathway, a non-discriminating aspartyl-tRNA synthetase (ND-AspRS) attaches Asp to tRNA(Asn) and the amidotransferase GatCAB transamidates the Asp to Asn on the tRNA. GatCAB can be similarly used for Gln-tRNA(Gln) formation. Most bacteria are predicted to use only one route for Asn-tRNA(Asn) formation. Given that Bacillus halodurans and Bacillus subtilis encode AsnRS for Asn-tRNA(Asn) formation and Asn synthetases to synthesize Asn and GatCAB for Gln-tRNA(Gln) synthesis, their AspRS enzymes were thought to be specific for tRNA(Asp). However, we demonstrate that the AspRSs are non-discriminating and can be used with GatCAB to synthesize Asn. The results explain why B. subtilis with its Asn synthetase genes knocked out is still an Asn prototroph. Our phylogenetic analysis suggests that this may be common among Firmicutes and 30% of all bacteria. In addition, the phylogeny revealed that discrimination toward tRNA(Asp) by AspRS has evolved independently multiple times. The retention of the indirect pathway in B. subtilis and B. halodurans likely reflects the ancient link between Asn biosynthesis and its use in translation that enabled Asn to be added to the genetic code. PMID- 26804572 TI - Introduction by Guest Editor. PMID- 26804573 TI - Giving the Self a Voice in MMPI Self-report: Jerry Wiggins and the Content Scales. AB - This article places one of Jerry Wiggins' contributions to the Minnesota Multiphasic Personality Inventory (MMPI), his content scales, in the twin contexts of past and recent research, and of Wiggins' own preoccupations growing out of the interpersonal point of view. It highlights Wiggins' perspective on the position of the person in the process of personality assessment, with special reference to the means by which the person's communication with the assessor may become accessible as a voice to be heard in the total pattern of assessment findings. Finally, one of the newer trends in personality assessment, one highly congenial to Wiggins' interpersonal outlook, is discussed with reference to the role that the MMPI-2 Content Scales may play in its future development. PMID- 26804571 TI - EASE-MM: Sequence-Based Prediction of Mutation-Induced Stability Changes with Feature-Based Multiple Models. AB - Protein engineering and characterisation of non-synonymous single nucleotide variants (SNVs) require accurate prediction of protein stability changes (DeltaDeltaGu) induced by single amino acid substitutions. Here, we have developed a new prediction method called Evolutionary, Amino acid, and Structural Encodings with Multiple Models (EASE-MM), which comprises five specialised support vector machine (SVM) models and makes the final prediction from a consensus of two models selected based on the predicted secondary structure and accessible surface area of the mutated residue. The new method is applicable to single-domain monomeric proteins and can predict DeltaDeltaGu with a protein sequence and mutation as the only inputs. EASE-MM yielded a Pearson correlation coefficient of 0.53-0.59 in 10-fold cross-validation and independent testing and was able to outperform other sequence-based methods. When compared to structure based energy functions, EASE-MM achieved a comparable or better performance. The application to a large dataset of human germline non-synonymous SNVs showed that the disease-causing variants tend to be associated with larger magnitudes of DeltaDeltaGu predicted with EASE-MM. The EASE-MM web-server is available at http://sparks-lab.org/server/ease. PMID- 26804574 TI - Interpersonal Perceptions of the Five-Factor Model of Personality: An Examination Using the Structural Summary Method for Circumplex Data. AB - Research investigating the structural convergence of the Interpersonal Circumplex (IPC; Wiggins, 1979, 1995) with the Five Factor Model (FFM; Costa & McCrae, 1992) of personality has predominantly focused on the traits of Agreeableness and Extraversion. The characteristics of the other three FFM traits: Neuroticism, Openness, and Conscientiousness are often regarded as largely intrapsychic. This study assessed interpersonal perceptions of the FFM traits emphasized in target descriptions by examining respondents' ratings of a target's interpersonal style. In an attempt to isolate the interpersonal aspects of each FFM trait, descriptions of fictional individuals were created that contained information relevant to being extremely high or low on a single FFM trait. Female and male versions were created to ensure gender has no effect on the interpersonal perceptions of the fictitious individual. The 462 participants received a paragraph description of an individual and were instructed to rate the individual on the Interpersonal Adjective Scales (IAS; Wiggins, 1995) based on the target description. Their responses were evaluated using Gurtman's (1994) structural summary approach to describe circumplex data. Based on the results for Extraversion and Agreeableness targets, the descriptions appear to be a valid approach in eliciting previous empirically supported interpersonal perceptions of the FFM. A 5 (Trait) x 2 (Polarity) x 2 (Gender) MANOVA found significant main effects for trait and polarity, and a significant trait x polarity interaction. No gender differences were found. The consistent fit of ratings data to the circumplexical cosine curve examined within the structural summaries supports propositions by several researchers that all FFM traits contain agentic and communal qualities as measured by the IAS. PMID- 26804575 TI - On the Relationship Between Circumplexes: Affect and Wiggins' IAS. AB - This article offers a new method to describe the relationship between two circumplexes, illustrated empirically with Wiggins' (1995) Interpersonal Adjective Scales (IAS) and Yik, Russell, and Steiger's (2004) 12-Point Affect Circumplex Scales (12-PACS). Michael Browne's CIRCUM-extension procedure was used to place each circumplex within the other. Simulations showed this procedure can reveal the number of dimensions of overlap between the two and can estimate the magnitude and location of the overlap. The IAS space overlaps the 12-PACS space on one axis, which falls at 35 degrees within the 12-PACS space (pleasant activated versus unpleasant deactivated) and at 71 degrees within the IAS space, which is close to where Extraversion (Factor I of the Five Factor Model) also lies. PMID- 26804576 TI - Where is the Personality in Personality Disorder Assessment? A Comparison Across Four Sets of Personality Disorder Scales. AB - The present research examined the amount and kind of personality measured within four sets of personality disorder (PD) scales. Three samples of undergraduate students (Ns = 326, 537, and 617) completed at least one PD measure and a combined interpersonal circumplex model (ICM) and five-factor model (FFM) measure. The FFM dimensions were found to account for between 5% to 57% of the variance in personality disorder symptomatology depending on the PD examined and the PD measure employed. Consistent with previous research, Neuroticism and low Extraversion often emerged as the primary predictors of PD symptomatology, but variability in the particular aspects of personality assessed within each of the PD measures was apparent within the ICM and FFM findings. The implications of the findings for conceptualization and measurement of PDs are discussed. PMID- 26804577 TI - The Impact of Item Characteristics on Item and Scale Validity. AB - This study describes the relation between personality items' validities, defined as the items' correlations with acquaintance ratings on the Big 5 personality factors, and other itemmetric properties including ambiguity, syntactic complexity, social desirability, content, and trait indicativity. Five external validity coefficients for each item on the California Psychological Inventory were correlated with a number of itemmetric variables often assumed to affect item validity. Item validity correlated positively with social desirability and trait indicativity and negatively with ambiguity across the five factors. Other characteristics had a more limited influence on item validity. Multiple regression analyses revealed trait indicativity -- how obviously an item response indicates a trait -- to be the most important determinant of item validity. Scales built from itemmetrically sound versus poor items showed differential validity in two additional samples. Implications for the psychological processes underlying responses to personality items are discussed. PMID- 26804578 TI - Two Replicable Suppressor Situations in Personality Research. AB - Suppressor situations occur when the simultaneous inclusion of two predictors improves one or both validities. A common allegation is that suppressor effects rarely replicate and have little substantive import. We present substantive examples from two established research domains to counter this skepticism. In the first domain, we show how measures of guilt and shame act consistently as mutual suppressors: Adding shame into a regression equation increases the negative association between guilt and aggression, whereas adding guilt increases the positive association between shame and aggression. In the second domain, we show how the effects of self-esteem and narcissism operate consistently as mutual suppressors: That is, adding narcissism into a regression equation increases the negative association between self-esteem and antisocial behavior, whereas adding self-esteem increases the positive association between narcissism and antisocial behavior. Discussion addresses the different implications for suppressors in theoretical and variable selection applications. PMID- 26804579 TI - Psychometric Properties of the HEXACO Personality Inventory. AB - We introduce a personality inventory designed to measure six major dimensions of personality derived from lexical studies of personality structure. The HEXACO Personality Inventory (HEXACO-PI) consists of 24 facet-level personality trait scales that define the six personality factors named Honesty-Humility (H), Emotionality (E), Extraversion (X), Agreeableness (A), Conscientiousness (C), and Openness to Experience (O). In this validation study involving a sample of over 400 respondents, all HEXACO-PI scales showed high internal consistency reliabilities, conformed to the hypothesized six-factor structure, and showed adequate convergent validities with external variables. The HEXACO factor space, and the rotations of factors within that space, are discussed with reference to J. S. Wiggins' work on the circumplex. PMID- 26804580 TI - The Early Development of the Interpersonal System of Personality (ISP). AB - This note sketches aspects of the development of the Interpersonal System of Personality (ISP), using information appearing in dissertations, theses, notes, correspondence, and publications prior to the classic 1951 paper by M. B. Freedman, T. F. Leary, A. G. Ossorio, and H. S. Coffey. Topics include the setting and the creation of the ISP, the authors' objective empirical investigation of the process of group therapy, and the accompanying growth in understanding from an initial, largely psychoanalytic orientation, to an explicitly interpersonal theory. Kurt Lewin's "field" and "vector" theories, Harry Stack Sullivan's "interpersonal force field," relevant classification schemes by others, and some neglected or poorly understood details of this history are presented. PMID- 26804581 TI - Clinical Practice Guideline: Chiropractic Care for Low Back Pain. AB - OBJECTIVE: The purpose of this article is to provide an update of a previously published evidence-based practice guideline on chiropractic management of low back pain. METHODS: This project updated and combined 3 previous guidelines. A systematic review of articles published between October 2009 through February 2014 was conducted to update the literature published since the previous Council on Chiropractic Guidelines and Practice Parameters (CCGPP) guideline was developed. Articles with new relevant information were summarized and provided to the Delphi panel as background information along with the previous CCGPP guidelines. Delphi panelists who served on previous consensus projects and represented a broad sampling of jurisdictions and practice experience related to low back pain management were invited to participate. Thirty-seven panelists participated; 33 were doctors of chiropractic (DCs). In addition, public comment was sought by posting the consensus statements on the CCGPP Web site. The RAND UCLA methodology was used to reach formal consensus. RESULTS: Consensus was reached after 1 round of revisions, with an additional round conducted to reach consensus on the changes that resulted from the public comment period. Most recommendations made in the original guidelines were unchanged after going through the consensus process. CONCLUSIONS: The evidence supports that doctors of chiropractic are well suited to diagnose, treat, co-manage, and manage the treatment of patients with low back pain disorders. PMID- 26804582 TI - Bioavailability study of arsenic and mercury in traditional Chinese medicines (TCM) using an animal model after a single dose exposure. AB - Traditional Chinese medicines (TCM) are increasingly being used as alternative medicines in many countries, and this has caused concern because of adverse health effects from toxic metal bioavailability such as mercury (Hg) and arsenic (As). The aim of this study was to investigate the bioavailability of As and Hg from TCM after a single exposure dose using an animal model of female Sprague Dawley rats. The rats were divided into 6 groups which included four groups treated with sodium arsenite (NaAsO2), arsenic sulfide (As2S3), mercuric chloride (HgCl2), mercuric sulfide (HgS), and two groups treated with TCM containing high Hg or As (Liu Shen Wan: As 7.7-9.1% and Hg 1.4-5.0%; Niuhang Jie du Pian: As 6.2 7.9% and Hg <0.001%). The samples of urine, faeces, kidney and liver were collected for analysis and histological assay. The results indicated that relatively low levels of As and Hg from these TCM were retained in liver and kidney tissues. The levels of As in these tissues after TCM treatment were consistent with the levels from the As sulphide treated group. With the exception of the mercuric chloride treated group, the levels of Hg in urine from other groups were very low, and high levels of As and Hg from TCM were excreted in faeces. The study showed poor bioavailability of As and Hg from TCM as indicated by low relative bioavailability of As (0.60-1.10%) and Hg (<0.001%). Histopathological examination of rat kidney and liver tissues did not show toxic effects from TCM. PMID- 26804584 TI - Optimizing force spectroscopy by modifying commercial cantilevers: Improved stability, precision, and temporal resolution. AB - Atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) enables a wide array of studies, from measuring the strength of a ligand-receptor bond to elucidating the complex folding pathway of individual membrane proteins. Such SMFS studies and, more generally, the diverse applications of AFM across biophysics and nanotechnology are improved by enhancing data quality via improved force stability, force precision, and temporal resolution. For an advanced, small format commercial AFM, we illustrate how these three metrics are limited by the cantilever itself rather than the larger microscope structure, and then describe three increasingly sophisticated cantilever modifications that yield enhanced data quality. First, sub-pN force precision and stability over a broad bandwidth (Deltaf=0.01-20Hz) is routinely achieved by removing a long (L=100MUm) cantilever's gold coating. Next, this sub-pN bandwidth is extended by a factor of ~50 to span five decades of bandwidth (Deltaf=0.01-1000Hz) by using a focused ion beam (FIB) to modify a shorter (L=40MUm) cantilever. Finally, FIB-modifying an ultrashort (L=9MUm) cantilever improves its force stability and precision while maintaining 1-MUs temporal resolution. These modified ultrashort cantilevers have a reduced quality factor (Q~0.5) and therefore do not apply a substantial (30 90pN), high-frequency force modulation to the molecule, a phenomenon that is unaccounted for in traditional SMFS analysis. Currently, there is no perfect cantilever for all applications. Optimizing AFM-based SMFS requires understanding the tradeoffs inherent to using a specific cantilever and choosing the one best suited to a particular application. PMID- 26804585 TI - Direct synthesis of doubly deprotonated, dearomatised lutidine PNP Cr and Zr pincer complexes based on isolated K and Li ligand transfer reagents. AB - Double deprotonation of 2,6-bis-(di-tert-butylphosphinomethyl)-pyridine ((tBu)PN(tBu)P), with KCH2C6H5 afforded K2((tBu)P*Na(tBu)P*), Na = anionic amido N, (tBu)P* = di-tert-butyl vinylic P donor. The analogous [Li2((tBu)P*Na(tBu)P*)]2 (1) was reacted with [CrCl2(THF)2] and [ZrCl4(THT)2] to give the helical [Cr{Cr((tBu)P*Na(tBu)P*)Cl}2] (2) and [Zr((tBu)P*Na(tBu)P*)Cl2] (3), respectively. DFT calculations support dearomatisation of P*NaP* and its high donor ability. PMID- 26804586 TI - How Mental Health Is Shortchanged by Lack of Reimbursement for Vagus Nerve Stimulation. PMID- 26804583 TI - Differences in Pain Coping Between Black and White Americans: A Meta-Analysis. AB - Compared with white individuals, black individuals experience greater pain across clinical and experimental modalities. These race differences may be due to differences in pain-related coping. Several studies examined the relationship between race and pain coping; however, no meta-analytic review has summarized this relationship or attempted to account for differences across studies. The goal of this meta-analytic review was to quantify race differences in the overall use of pain coping strategies as well as specific coping strategies. Relevant studies were identified using electronic databases, an ancestry search, and by contacting authors for unpublished data. Of 150 studies identified, 19 met inclusion criteria, resulting in 6,489 participants and 123 effect sizes. All of the included studies were conducted in the United States. Mean effect sizes were calculated using a random effects model. Compared with white individuals, black individuals used pain coping strategies more frequently overall (standardized mean difference [d] = .25, P < .01), with the largest differences observed for praying (d = .70) and catastrophizing (d = .40). White individuals engaged in task persistence more than black individuals (d = -.28). These results suggest that black individuals use coping strategies more frequently, specifically strategies associated with poorer pain outcomes. Future research should examine the extent to which the use of these strategies mediates race differences in the pain experience. PERSPECTIVE: Results of this meta-analysis examining race differences in pain-related coping indicate that, compared with white individuals, black individuals use coping strategies more frequently, specifically those involving praying and catastrophizing. These differences in coping may help to explain race differences in the pain experience. PMID- 26804587 TI - Diamidophosphines with six-membered chelates and their coordination chemistry with group 4 metals: development of a trimethylene-methane-tethered [PN2]-type "molecular claw". AB - The coordination chemistry of the phosphine-tethered diamidophosphine ligands PhP(CH2CH2CH2NHPh)2 (pr[NPN]H2) and PhP(1,2-CH2-C6H4-NHSiMe3)2 (bn[NPN]H2) featuring six-membered N-C3-P chelates was explored with group 4 metals, which allowed for the consecutive development of a new trimethylene-methane-tethered [PN2] scaffold. In the case of the propylene-linked system pr[NPN]H2, access to the sparingly soluble dibenzyl derivative pr[NPN]ZrBn2 (3-Zr) was gained, while thermally sensitive zirconium and hafnium diiodo complexes bn[NPN]MI2 (5-M, M = Zr, Hf) were isolated in the case of the benzylene-linked derivative bn[NPN]H2. Despite the related phosphine-tethered backbone architectures of both of these ligands, their group 4 complexes were found to exhibit either C1-symmetric (bn[NPN]MX2) or averaged CS-symmetric (pr[NPN]MX2) structures in solution. To restrain the overall flexibility of these systems and thereby control the properties of the resulting complexes without disrupting the six-membered chelates, the new trimethylene-methane-tethered N,N'-di-(tert-butyl)-substituted [PN2]H2 protioligand was designed. This tripodal ligand system was prepared on a gram scale and its CS-symmetric dichloro complexes [PN2]MCl2 (6-M, M = Ti, Zr, Hf) were isolated subsequently. The benzene-soluble dibenzyl derivative [PN2]ZrBn2 (7-Zr) was synthesised as well and characterised by X-ray diffraction. These results are discussed not only in conjunction with the known [NPN] coordinated group 4 complexes incorporating five-membered chelates, but also in the context of "molecular claws" that are related to the new [PN2] tripod. PMID- 26804588 TI - Perioperative use of centrally acting angiotensin-converting enzyme inhibitor may increase patients' risk for postoperative nausea and vomiting. AB - Substance P (SP) is involved in the development of postoperative nausea and vomiting (PONV). It is hydrolyzed by angiotensin-converting enzyme (ACE). Centrally acting ACE inhibitors (CACE-Is) are widely used in the perioperative period. The current evidence showed CACE-Is could upregulate SP level in the central nervous system which may contribute to the occurrence of PONV in 0-72 h. Here, we present our hypothesis that the use of CACE-Is in the perioperative period may increase patients' risk for both early (0-24h) and late (24-72 h) PONV. The identification of this new risk factor may improve patients' risk assessment and thus lead to better prophylaxis strategies for PONV that are base on risk stratification. PMID- 26804589 TI - CSF generation by pineal gland results in a robust melatonin circadian rhythm in the third ventricle as an unique light/dark signal. AB - Pineal gland is an important organ for the regulation of the bio-clock in all vertebrate species. Its major secretory product is melatonin which is considered as the chemical expression of darkness due to its circadian peak exclusively at night. Pineal melatonin can be either released into the blood stream or directly enter into the CSF of the third ventricle via the pineal recess. We have hypothesized that rather than the peripheral circulatory melatonin circadian rhythm serving as the light/dark signal, it is the melatonin rhythm in CSF of the third ventricle that serves this purpose. This is due to the fact that melatonin circadian rhythm in the CSF is more robust in terms of its extremely high concentration and its precise on/off peaks. Thus, extrapineal-generated melatonin or diet-derived melatonin which enters blood would not interfere with the bio clock function of vertebrates. In addition, based on the relationship of the pineal gland to the CSF and the vascular structure of this gland, we also hypothesize that pineal gland is an essential player for CSF production. We feel it participates in both the formation and reabsorption of CSF. The mechanisms associated with these processes are reviewed and discussed in this brief review. PMID- 26804590 TI - Atrial fibrillation: In the light of new hypothesis. AB - BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Many studies have investigated the cause for the development of AF, however, the question remains unanswered. METHODS: A comparison of hydrodynamics between AF and sinus rhythm was performed. RESULTS: I proposed the hypothesis that atrial fibrillation is a protective physiological mechanism, based on the termination of atrial mechanical systole. This reduces the pressure in the system of the pulmonary veins and alveolar capillaries in pathological situations, and thus reduces the likelihood for development of pulmonary congestion and edema. CONCLUSIONS: The hypothesis is well correlated with the known facts and phenomenons associated with AF, and explains the causes of the onset of AF in different conditions and diseases. PMID- 26804591 TI - In-situ expression of Interleukin-18 and associated mediators in the human brain of sALS patients: Hypothesis for a role for immune-inflammatory mechanisms. AB - Recent studies reported over-expression of a cytokine (Interleukin (IL)-18) in the serum of sporadic amyotrophic lateral sclerosis (sALS) patients. Here, we report on the first-time detection of in-situ expression of activated IL-18 in the human brain in sALS patients. We also detected cerebral in-situ expression of key-molecules known to be closely related to the molecular network associated with the activation/secretion of IL-18 cytokine, namely, the receptor-interacting serine/threonine-protein kinase 3 (RIPK3 or RIP3), NOD-like receptor pyrin domain containing 3 (NLRP3)-inflammasome, and activated caspase-1. These findings suggest and allow to hypothesize that there might be a role for this cytokine network in molecular mechanisms associated with or implicated in the physiopathology of this neurodegenerative disorder. PMID- 26804592 TI - Multiple Integrated Complementary Healing Approaches: Energetics & Light for bone. AB - A synergistic-healing strategy that combines molecular targeting within a system wide perspective is presented as the Multiple Integrated Complementary Healing Approaches: Energetics And Light (MICHAEL). The basis of the MICHAEL approach is the realization that environmental, nutritional and electromagnetic factors form a regulatory framework involved in bone and nerve healing. The interactions of light, energy, and nutrition with neural, hormonal and cellular pathways will be presented. Energetic therapies including electrical, low-intensity pulsed ultrasound and light based treatments affect growth, differentiation and proliferation of bone and nerve and can be utilized for their healing benefits. However, the benefits of these therapies can be impaired by the absence of nutritional, hormonal and organismal factors. For example, lack of sleep, disrupted circadian rhythms and vitamin-D deficiency can impair healing. Molecular targets, such as the Wnt pathway, protein kinase B and glucocorticoid signaling systems can be modulated by nutritional components, including quercetin, curcumin and Mg(2+) to enhance the healing process. The importance of water and water-regulation will be presented as an integral component. The effects of exercise and acupuncture on bone healing will also be discussed within the context of the MICHAEL approach. PMID- 26804593 TI - The role of the hippocampus in the pathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). AB - Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a severe acquired illness characterized by a profound sensation of fatigue, not ameliorated by rest and resulting in a substantial decrease in the amount and quality of occupational, social and recreational activities. Despite intense research, the aetiology and pathogenesis of ME/CFS is still unknown and no conclusive biological markers have been found. As a consequence, an accepted curative treatment is still lacking and rehabilitation programmes are not very effective, as few patients recover. Increased knowledge of the mechanisms leading to the emergence and maintenance of the illness is called for. In this study, I will put forth an alternative hypothesis to explain some of the pathologies associated with ME/CFS, by concentrating on one of the major strategic organs of the brain, the hippocampus. I will show that the ME/CFS triggering factors also impact the hippocampus, leading to neurocognitive deficits and disturbances in the regulation of the stress system and pain perception. These deficits lead to a substantial decrease in activity and to sleep disorders, which, in turn, impact the hippocampus and initiate a vicious circle of increased disability. PMID- 26804594 TI - The proposed use of radiofrequency ablation for the treatment of fistula-in-ano. AB - Fistula in ano is a very common presentation to colorectal clinic. Embarrassment due to the symptoms makes accurate estimations of incidence difficult. It is estimated that up to 40% of peri-anal abscess will be accompanied by or preceded by a fistula. Fistulae can be classified into simple fistulae that involve no or minimal sphincter muscle and complex, which involve significant amounts of the anal sphincter muscle, possibly with multiple tracts. For complex fistulae a seton suture is usually placed through the tract and out through the anus to form a loop allowing pockets of sepsis to drain internally and externally and a mature tract of fibrous tissue to develop. Following this period definitive fistula treatment is considered. This can involve a number of procedures that have tremendously varied success rates in the literature. The first stage of surgical treatment is often a core fistulectomy, which entails surgical removal of the tract. This may be followed by insertion of fibrin glue, a collagen plug or formation of a rotation skin flap from surrounding tissue in order to close the resultant tissue defect. All current treatments have a significant failure rate. If this wound breaks down the surgery can leave a large painful peri-anal wound that can lead to ongoing fistulation. Should this occur resiting of the seton will be required with the patient only getting back to square one after months of healing around the seton. In addition removing cores of fibrous tissue passing through the sphincter can threaten the sphincter function resulting in impaired continence. Having seen radiofrequency ablation used to close varicose veins the authors propose that one could use similar techniques to close a fibrous tract matured with a seton in order to close a fistula. The authors propose that a short length radiofrequency catheter could be used to treat fistula in ano. This would in theory be less painful with less tissue destruction. In addition there would be no necessity for extensive incisions. As the energy penetration can be controlled the procedure will be safe even if it fails, without causing a large wound or tissue necrosis. All other treatment options will still be available. PMID- 26804595 TI - Mechanism of subdural effusion evolves into chronic subdural hematoma: IL-8 inducing neutrophil oxidative burst. AB - Chronic subdural hematoma (CSDH) is still a mysterious disease. Though great success has been has achieved by neuro-surgery treatment, the origin and development of CSDH remains unknown. Tremendous clinical observations have found the correlation of subdural effusion (SDE) and CSDH. However, systematic elucidation of CSDH's origin and progression is lacking while almost all the current hypothesis only explained partial phenomenon. This hypothesis proposes Interleukin (IL)-8 inducing neutrophil respiratory burst is the crucial impact when SDE evolves into CSDH. IL-8 initially secreted by dural border layer cells, accumulates and the concentration of IL-8 rises in the SDE cavity. Accompanied by the formation of neo-membrane under the dura meninges, IL-8 firstly prompts to establish the neo-vasculature in it, and then attracts lymphocytes aggregation in the neo-membrane. Both the newly recruited lymphocytes and endothelial cells assist the further elevation of local IL-8 concentration. When the IL-8 concentration elevated to a particular level, it attracts neutrophils to the inner wall of neo-vessels and primes them to oxidative burst. Lysosomes and superoxide released by these neutrophils make the fragile neo-capillary became leaky, and subsequently the plasma and blood cells run into SDE. However, as long as the erythrocytes come into the cavity, they shall bind large quantity of IL-8 and decrease IL-8 concentration to a lower level relatively that reduce the neutrophils recruit. When this negative feedback is stagnancy, for example, the SDE space is so large in elder man who is experiencing brain atrophy, the neo vessels have to release more erythrocytes to bind IL-8, the liquid cavity will expand and the high intracranial pressure symptoms appeared. Our hypothesis holds potential for the proper therapeutic intervention of CSDH. IL-8 antagonist and other anti-inflammation drugs like macrolides antibiotics, glucocorticoid and atorvastatin might be optional to resist the liquid cavity expanding as actually occurs obvious bleeding soon. PMID- 26804596 TI - The case for aflatoxins in the causal chain of gallbladder cancer. AB - Chronic aflatoxin exposure has long been related to hepatocellular carcinoma (HCC). Recently, its association with gallbladder cancer (GBC) was postulated. Here we present the data supporting this hypothesis in Chile, the country with the highest GBC mortality worldwide with age-standardized mortality rates (ASMR) of 10.3 in women and 5.04 in men. The highest GBC rates occur in Southern Chile (ASMR=18), characterized by: high Amerindian ancestry, associated with high bile acid synthesis and gallstones; high poverty and high cereal agriculture, both associated with aflatoxin exposure. Aflatoxins have been detected in imported and locally grown foods items. We estimated population dietary exposure ranging from 0.25 to 35.0 ng/kg-body weight/day. The only report on human exposure in Chile found significantly more aflatoxin biomarkers in GBC than in controls (Odds Ratio=13.0). The hypothesis of aflatoxin-GBC causal link in the Chilean population is supported by: genetically-determined rapid cholesterol excretion and high gallstones prevalence (49.4%); low prevalence of HCC (ASMR=4.9) and low HBV infection (0.15%) the main co-factor of aflatoxins in HCC risk. If the association between aflatoxins and GBC were confirmed, public health interventions based on food regulation could have a substantial public health impact. PMID- 26804597 TI - Human breast milk and adipokines--A potential role for the soluble leptin receptor (sOb-R) in the regulation of infant energy intake and development. AB - Concentrations of different adipokines in human breast milk are thought to be able to affect energy intake of the infant. Leptin is a hormone synthesized by adipose tissue and the human placenta and favors satiety. The availability of leptin in breast milk is influenced by epithelial cells of the mammary gland that are known to be able to produce leptin, as well as leptin from maternal circulation that is transported to the breast milk, and which can thus in turn reach neonatal blood after absorption. Research so far as mainly focused on leptin concentrations in breast milk. However, evidence suggests that in addition to leptin concentrations levels of the so-called soluble leptin receptor (sOb-R), the main high-affinity binding protein for leptin in humans, are necessary in order to calculate the free leptin index (FLI) and to assess function of the leptin axis. FLI is calculated from the ratio of leptin to the sOb-R, and serves as the main parameter for assessing function of the leptin axis throughout maturation and development. Here we propose that assessing sOb-R levels in addition to leptin concentrations in breast milk could serve as a valuable tool to investigate effects of the leptin axis in breast milk because sOb-R concentrations can impact available leptin levels, and which in turn can have significant implications for infant energy intake and related development. PMID- 26804598 TI - Targeting tumor-associated immune suppression with selective protein kinase A type I (PKAI) inhibitors may enhance cancer immunotherapy. AB - Despite the tremendous progress in last few years, the cancer immunotherapy has not yet improved disease-free because of the tumor-associated immune suppression being a major barrier. Novel trends to enhance cancer immunotherapy aims at harnessing the therapeutic manipulation of signaling pathways mediating the tumor associated immune suppression, with the general aims of: (a) reversing the tumor immune suppression; (b) enhancing the innate and adaptive components of anti tumor immunosurveillance, and (c) protecting immune cells from the suppressive effects of T regulatory cells (Tregs) and the tumor-derived immunoinhibitory mediators. A particular striking example in this context is the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A type I (PKAI) pathway. Oncogenic cAMP/PKAI signaling has long been implicated in the initiation and progression of several human cancers. Emerging data indicate that cAMP/PKAI signaling also contributes to tumor- and Tregs-derived suppression of innate and adaptive arms of anti-tumor immunosurveillance. Therapeutically, selective PKAI inhibitors have been developed which have shown promising anti-cancer activity in pre-clinical and clinical settings. Rp-8-Br-cAMPS is a selective PKAI antagonist that is widely used as a biochemical tool in signal transduction research. Collateral data indicate that Rp-8-Br-cAMPS has shown immune-rescuing potential in terms of enhancing the innate and adaptive anti-tumor immunity, as well as protecting adaptive T cells from the suppressive effects of Tregs. Therefore, this proposal specifically implicates that combining selective PKAI antagonists/inhibitors with cancer immunotherapy may have multifaceted benefits, such as rescuing the endogenous anti-tumor immunity, enhancing the efficacy of cancer immunotherapy, and direct anti-cancer effects. PMID- 26804599 TI - Deep venous thrombosis: The valve cusp hypoxia thesis and its incompatibility with modern orthodoxy. AB - The valve cusp hypoxia thesis (VCHT) of the aetiology of deep venous thrombosis (DVT) was adumbrated in this journal in 1977 and fully articulated in 2008, the original hypothesis having been strongly corroborated by experiments published in 1981 and 1984. It presents a unitary account of the pathogenesis of venous thrombosis and embolism that is rooted in the pathophysiological tradition of Hunter, Virchow, Lister, Welch and Aschoff, a tradition traceable back to Harvey. In this paper we summarise the thesis in its mature form, consider its compatibility with recent advances in the DVT field, and ask why it has not yet been assimilated into the mainstream literature, which during the past half century has been dominated by a haematology-orientated 'consensus model'. We identify and discuss seven ways in which the VCHT is incompatible with these mainstream beliefs about the aetiology of venous thrombosis, drawing attention to: (1) the spurious nature of 'Virchow's triad'; (2) the crucial differences between 'venous thrombus' and 'clot'; the facts that (3) venous thrombi form in the valve pockets (VVPs), (4) DVT is not a primarily haematological condition, (5) the so-called 'thrombophilias' are not thrombogenic per se; (6) the conflict between the single unitary aetiology of DVT and the tacit assumption that the condition is 'multicausal'; (7) the inability of anticoagulants to prevent the initiation of venous thrombogenesis, though they do prevent the growth of thrombi to clinically significant size. In discussing point (7), we show that the VCHT indicates new approaches to mechanical prophylaxis against DVT. These approaches are then formulated as experimentally testable hypotheses, and we suggest methods for testing them preclinically using animal trials. PMID- 26804600 TI - Hepatocellular carcinoma and estrogen receptors: Polymorphisms and isoforms relations and implications. AB - Hepatocellular carcinoma (HCC) is the most common primary tumor of liver and its incidence continues to increase worldwide. HCC is a disease with multifactorial causes and genetic variability has been discussed as a risk factor for its development. Liver is a hormone-sensitive organ and therefore is influenced by gonadal hormones, such as estrogen. Estrogen is known to participate in various biological functions, but its role in development of HCC, on the other hand, is controversial and presents evidence suggesting a role as both a carcinogen and protective effect in liver. Estrogen way of action is mediated by estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta), that belong to a family of nuclear receptors that may regulate the expression of many genes. The ER subtypes exert a variety of roles in many stages of liver disease and may play a part in the process of signal transduction, according to some studies. However, the many functions of ER subtypes in hepatic diseases, in special of the ERbeta, are yet to be clarified. The genetic modifications related to HCC are not yet fully clarified and accumulation of multiple genetic alterations appears to have an important role in carcinogenesis of HCC. The presence of some certain single nucleotide polymorphism (SNP) may have a functional repercussion related to final product of a gene, which can be measured and may participate in some alterations related to a pathological condition. Our hypothesis is based on the fact that liver tissue express ER and its different variants exert multiple functions in various stages of liver disease and participate in an extremely complicated signal transduction process, therefore we believe that the presence of one or more SNPs of ESR1 and ESR2 genes may be related with the increase of risk in developing and the severity of HCC, as well as in the response to different treatments. The confirmation of our hypothesis by scientific studies may provide knowledge of markers that act as prognostic factors of this disease, as well as enabling alternatives to development of anti tumoral therapies. PMID- 26804601 TI - Hypothesis: Fingolimod explores new horizons in treatment of lymphoma. AB - Lymphomas (Hodgkin's (10%) and non-Hodgkin's (90%) lymphomas) are a group of blood cell tumors arising from lymphocytes and lymphadenopathy is the most common primary presentation of the disease. In non-Hodgkin lymphomas, the prognosis is worse. As the disease initiates, neoplastic cells may spread to and involve other lymph nodes and extra nodal regions. The disease is staged based on desperation of neoplastic cells and the prognosis highly depends on the stage of the disease at the time of diagnosis. Fingolimod is an immunomodulating drug, approved for treating relapsing forms of multiple sclerosis. Fingolimod impairs migration of lymphocytes from lymph nodes and it is hypothesized that Fingolimod could alleviate and decrease disease burden of lymphoma as it sequesters malignant cells within involved lymph nodes and it decelerates progression of the disease, increases efficacy of other treatment options and it is synergistic with anti VEGF medications, it is an anti-metastatic, anti-inflammatory, cytostatic/cytotoxic agent and it boosts function of immune system in deterioration of neoplastic cells. Therefore, the agent can be used not only to treat lymphoma, but also to control and prevent relapse of the disease in those who are remitted. PMID- 26804602 TI - Can we measure surgical resilience? AB - Surgical resilience describes psychological resilience within a surgical setting. Within a surgical setting, psychologically resilient patients have improved recovery and wound-healing. The search for biological correlates in resilient patients has led to the hypothesis that certain endogenous biomarkers (namely neuropeptide Y (NPY), testosterone, and dehydroepiandrosterone (DHEA)) are altered in resilient patients. The concept of surgical resilience raises the question of whether enhanced recovery following surgery can be demonstrated in patients with high titres of resilience biomarkers as compared to patients with low titres of resilience biomarkers. To determine the prognostic value of resilience biomarkers in surgical recovery, a cohort of patients undergoing major surgery should initially be psychometrically tested for their resilience levels before and after surgery so that biomarker levels of NPY, testosterone and DHEA can be compared to a validated psychometric test of resilience. The primary outcome would be length of hospital stay with and without an enhanced recovery program. Secondary outcome measures such as complications, time in rehabilitation and readmission could also be included. If the hypothesis is upheld, resilience biomarkers could be used to support more individualised perioperative management and lead to more efficient and effective allocation of healthcare resources. PMID- 26804603 TI - Exercise before and after SCUBA diving and the role of cellular microparticles in decompression stress. AB - Risk in SCUBA diving is often associated with the presence of gas bubbles in the venous circulation formed during decompression. Although it has been demonstrated time-after-time that, while venous gas emboli (VGE) often accompany decompression sickness (DCS), they are also frequently observed in high quantities in asymptomatic divers following even mild recreational dive profiles. Despite this VGE are commonly utilized as a quantifiable marker of the potential for an individual to develop DCS. Certain interventions such as exercise, antioxidant supplements, vibration, and hydration appear to impact VGE production and the decompression process. However promising these procedures may seem, the data are not yet conclusive enough to warrant changes in decompression procedure, possibly suggesting a component of individual response. We hypothesize that the impact of exercise varies widely in individuals and once tested, recommendations can be made that will reduce individual decompression stress and possibly the incidence of DCS. The understanding of physiological adaptations to diving stress can be applied in different diseases that include endothelial dysfunction and microparticle (MP) production. Exercise before diving is viewed by some as a protective form of preconditioning because some studies have shown that it reduces VGE quantity. We propose that MP production and clearance might be a part of this mechanism. Exercise after diving appears to impact the risk of adverse events as well. Research suggests that the arterialization of VGE presents a greater risk for DCS than when emboli are eliminated by the pulmonary circuit before they have a chance to crossover. Laboratory studies have demonstrated that exercise increases the incidence of crossover likely through extra-cardiac mechanisms such as intrapulmonary arterial-venous anastomoses (IPAVAs). This effect of exercise has been repeated in the field with divers demonstrating a direct relationship between exercise and increased incidence of arterialization. PMID- 26804604 TI - Does the mosquito have more of a role in certain cancers than is currently appreciated? - The mosquito cocktail hypothesis. AB - The International Agency for Research on Cancer recognises five viruses, one bacterium and three parasites as having a causal relationship to cancer, and one virus, HIV, that by suppressing the immune system assists in the development of cancer. In addition numerous researchers have claimed links between cancer and other viruses and bacteria, many of which have been isolated from tumours. Excluding the non-causal HIV, 33 infectious agents linked with cancer have been identified in the literature, 27 of which have one thing in common: they are all present in mosquitoes. There are over 3000 species of mosquito and very few have been fully analysed, so the six remaining infectious agents may be present in some unexamined species. This hypothesis proposes that more cancers than are presently appreciated may arise from the long-term outcome of a mosquito bite, which by releasing a complex cocktail of up to 60 infectious agents directly into the blood stream, often results in contemporaneous immuno-suppression and a multiplicity of co-infections. These co-infections may act synergistically in whole, or in part, and in complex ways. Whether and if so which type of cancer ensues will depend on the constituent ingredients in the cocktail, determined by multiple factors such as the mosquito's drinking and feeding patterns, number of previous blood-meals and the variety of intermediate hosts from which these meals are taken. Only a few mosquito species carry malaria, dengue fever, chikungunya and the other recognised serious human ailments. This hypothesis suggests that the number of species carrying the cancer cocktail will be few in number but collectively have a worldwide presence. PMID- 26804606 TI - The efficacy of a volunteer-administered cognitive stimulation program in long term care homes. AB - BACKGROUND: Cognitive impairment (CI) that arises in some older adults limits independence and decreases quality of life. Cognitive stimulation programs delivered by professional therapists have been shown to help maintain cognitive abilities, but the costs of such programming are prohibitive. The present study explored the feasibility and efficacy of using long-term care homes' volunteers to administer a cognitive stimulation program to residents. METHODS: Thirty-six resident participants and 16 volunteers were alternately assigned to one of two parallel groups: a control group (CG) or stimulation group (SG). For eight weeks, three times each week, CG participants met for standard "friendly visits" (casual conversation between a resident and volunteer) and SG participants met to work through a variety of exercises to stimulate residents' reasoning, attention, and memory abilities. Resident participants were pre- and post-tested using the Weschler Abbreviated Scale of Intelligence-Second Edition, Test of Memory, and Learning-Senior Edition, a modified Letter Sorting test (LS), Clock Drawing Test (CDT), and the Action Word Verbal Fluency Test. RESULTS: Two-way analyses of covariance (ANCOVA) controlling for dementia diagnosis indicated statistically greater improvements in the stimulation participants than in the control participants in Immediate Verbal Memory, p = 0.011; Non-Verbal Memory, p = 0.012; Learning, p = 0.016; and Verbal Fluency, p = 0.024. CONCLUSIONS: The feasibility and efficiency of a volunteer-administered cognitive stimulation program was demonstrated. Longitudinal studies with larger sample sizes are recommended in order to continue investigating the breadth and depth volunteer roles in the maintenance of the cognitive abilities of older adults. PMID- 26804605 TI - Identification of Most Aggressive Carcinoma Among Patients Diagnosed With Prostate Cancer Using Mathematical Modeling of Prostate-Specific Antigen Increases. AB - BACKGROUND: Tools for differentiating aggressive and indolent prostate carcinoma (PCa) are needed. Mathematical modeling is a promising approach for longitudinal analysis of tumor marker kinetics. PATIENTS AND METHODS: The prostate-specific antigen (PSA) increases from patients with PCa and those with benign prostatic hyperplasia (BPH) were retrospectively analyzed using a mathematical model. Using the NONMEM program, individual PSA kinetics were fit to the following equation: [d(PSA)/dt = (PROD.K * exp [RHO1 * t]) * (1 - BPH) + PROD.NK * exp (RHO2 * t) - KELIM * (PSA)], where RHO1 is the PSA production increase rate by PCa cells (PROD.K), RHO2 is the PSA production increase rate by non-PCa cells (PROD.NK), and KELIM is the PSA elimination rate. The comparative value of the modeled kinetic parameters, estimated for each patient, for predicting the D'Amico score and relapse-free survival (RFS) were tested using logistic regression analysis and multivariate survival tests. RESULTS: The PSA kinetics from 62 patients with BPH and 149 patients with PCa before radical prostatectomy were successfully modeled. We identified statistically significant relationships between the PSA growth rate related to cancer cells (RHO1) and the probability of D'Amico high risk group (less than the median RHO1 vs. at the median or greater: odds ratio, 2.15; 95% confidence interval [CI], 1.00-4.77; P = .05). RHO1 was also a significant prognostic factor for RFS on univariate analysis and against other reported prognostic factors using multivariate Cox tests. Three independent prognostic factors of RFS were found: RHO1 (hazard ratio [HR], 2.71; 95% CI, 1.25 5.84; P = .01), Gleason score (HR, 8.54; 95% CI, 4.19-17.40; P < .01), and positive surgical margins (HR, 2.04; 95% CI, 1.05-3.97; P = .03). CONCLUSION: Using a few PSA time points analyzed with a mathematical model (easily manageable in routine practice), it could be possible to determine before surgery whether a patient has presented with aggressive PCa. PMID- 26804607 TI - Clinical and Echocardiographic Factors Associated With New-Onset Atrial Fibrillation in Heart Failure - Subanalysis of the WARCEF Trial. AB - BACKGROUND: Heart failure (HF) patients have a high incidence of new-onset AF. Given the adverse prognostic influence of AF in HF, identifying patients at high risk of developing AF is important. METHODS AND RESULTS: The incidence and factors associated with new-onset AF were investigated in patients in sinus rhythm with reduced LVEF enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. Analyses involved clinical factors alone (n=2,219), and clinical plus echocardiographic findings (n=1,125). During 3.5+/-1.8 years of follow-up, 212 patients (9.6% of total cohort) developed AF. In both samples, new-onset AF was associated with age, male sex, White race, and IHD. Among echocardiographic variables, only LAD predicted AF. On multivariate Cox modeling, age (HR, 1.02; 95% CI: 1.00-1.03, P=0.008), IHD (HR, 1.37; 95% CI: 1.02-1.84, P=0.036) and LAD (HR, 1.48; 95% CI: 1.15-1.91, P=0.003) remained associated with AF onset. Patients with IHD, LAD>4.5 cm and age>50 years had a 2.5-fold higher risk of AF than patients without any of these characteristics (HR, 2.52; 95% CI: 1.72-3.69, P<0.0001). CONCLUSIONS: Age, IHD and LAD independently predict new-onset AF in HF patients in sinus rhythm, at younger age and smaller LAD than generally believed. This information may be useful to risk stratify HF patients for AF development, allowing close monitoring and possibly early detection. (Circ J 2016; 80: 619-626). PMID- 26804608 TI - Association of GCH1 and MIR4697, but not SIPA1L2 and VPS13C polymorphisms, with Parkinson's disease in Taiwan. AB - Recently, a large-scale meta-analysis of genome-wide association study (GWAS) data identified several new risk loci that can modulate the risk of Parkinson's disease (PD). These associations have yet to be examined in PD patients in Chinese or Asian population. Because ethnic-specific effect is an important concern for GWAS analysis, we genotyped single-nucleotide polymorphisms in the new genetic loci, GCH1 (rs11158026), SIPA1L2 (rs10797576), VPS13C (rs2414739), and MIR4697 (rs329648), to investigate their associations with risk of PD in Taiwan. Another single-nucleotide polymorphism GCH1 rs7155501, previously identified by GWAS listed at the top 20 genes in PDGene database was also included. A total of 1151 study subjects comprising 598 patients with PD and 553 unrelated healthy controls were recruited. The frequency of minor allele (C allele) of GCH1 rs11158026 was found to be significantly higher in PD cases than in controls (p = 0.003). The CC genotype of rs11158026 increased PD risk compared to TT genotype (odds ratio [OR] = 1.29, 95% confidence interval [CI] = 1.09, 1.53, p = 0.004). Under additive model, the GCH1 rs11158026 increased the risk of developing PD (OR = 1.30, 95% CI = 1.10, 1.54, p = 0.002). In recessive model, the genotype TT of MIR4697 rs329648 marginally decreased the PD risk (OR = 0.62, 95% CI = 0.43, 0.90, p = 0.01). The PD patients demonstrated similar genotypic and allelic frequencies in GCH1 rs7155501, SIPA1L2 rs10797576, and VPS13C rs2414739 with the controls. These findings suggest that the GCH1 and MIR4697 but not SIPA1L2 and VPS13C are genetic loci influencing risk of PD in Taiwan. PMID- 26804609 TI - Mutational analysis of TBK1 in Taiwanese patients with amyotrophic lateral sclerosis. AB - Mutations in the TBK1 gene were just recently identified to cause amyotrophic lateral sclerosis (ALS), and their role in ALS in various populations remains unclear. The aim of this study was to determine the frequency and spectrum of mutations in TBK1 in a Taiwanese ALS cohort of Han Chinese origin. Mutational analyses of TBK1 were carried out by direct nucleotide sequencing in a cohort of 207 unrelated patients with ALS. Among them, the genetic diagnoses of 168 patients remained elusive after mutations in SOD1, C9ORF72, TARDBP, FUS, ATXN2, OPTN, VCP, UBQLN2, SQSTM1, PFN1, HNRNPA1, HNRNPA2B1, MATR3, CHCHD10, and TUBA4A had been excluded. We identified one nonsense mutation, p.R444X (c.1330C>T), in one patient with apparently sporadic ALS-frontotemporal dementia. In vitro functional study demonstrated the p.R444X mutation resulting in a truncated TANK binding kinase 1 (TBK1) protein product, low protein expression, and loss of kinase function and interaction with optineurin. The frequency of TBK1 mutations in ALS patients in Taiwan is, therefore, approximately 0.5% (1/207). This study reports a novel TBK1 mutation and stresses on the importance to consider TBK1 mutation as a possible etiology of ALS. PMID- 26804610 TI - The impact of national accreditation reform on survey reliability: a 2-year investigation of survey coordinators' perspectives. AB - RATIONALE, AIMS AND OBJECTIVE: Accrediting health care organizations against standards is a recognized safety and quality intervention. The credibility of an accreditation programme relies on surveying reliability. We investigated accreditation survey coordinators' perceptions of reliability issues and their continued relevancy, during a period of national accreditation reform. METHOD: In 2013 and 2014, questionnaire surveys were developed using survey coordinators' feedback of their experiences and concerns regarding the accreditation process. Each year, a purpose-designed questionnaire survey was administered during the accrediting agency survey coordinator training days. RESULTS: Participants reported that survey reliability was informed by five categories of issues: the management of the accreditation process, including standards and health care organizational issues; surveyor workforce management; survey coordinator role; survey team; and individual surveyors. A new accreditation system and programme did not alter the factors reported to shape survey reliability. However, across the reform period, there was a noted change within each category of the specific issues that were of concern. Furthermore, consensus between coordinators that existed in 2013 appears to have diminished in 2014. Across all categories, in 2014 there was greater diversity of opinion than in 2013. CONCLUSIONS: The known challenges to the reliability of an accreditation programme retained their potency and relevancy during a period of reform. The diversity of opinion identified across the coordinator workforce could potentially place the credibility and reliability of the new scheme at risk. The study highlights that reliability of an accreditation scheme is an ongoing achievement, not a one-off attainment. PMID- 26804612 TI - Effect of acidification on the protection of alginate-encapsulated probiotic based on emulsification/internal gelation. AB - BACKGROUND: The method of emulsification/internal gelation is commonly used to prepare alginate microspheres for lactic acid bacteria (LAB). This paper focused on the influence of acidification parameters, i.e. acid/Ca molar ratio and acidification time, on the physical properties and cell protection efficiency of microspheres and their correlations. RESULTS: With increasing acid/Ca molar ratio and acidification time, the average diameter of microspheres decreased and their mechanical strength increased. Interestingly, wet alginate microspheres shrank in simulated gastric juice (SGJ) while they swelled in bile salts solution (BS). The shrinkage or swelling ratio decreased with increasing mechanical strength. Correlation analysis showed that the encapsulated cell survivals in both SGJ and BS were positively correlated with the mechanical strength of microspheres but negatively with the shrinkage or swelling ratio. BacLight LIVE/DEAD assay suggested that the viability of encapsulated cells in fresh, SGJ-treated and BS treated microspheres was closely related to cell membrane integrity. CONCLUSION: Acidification is a key step during microsphere preparation, which strongly affected the physical properties of alginate microspheres, resulting in different cell protection efficiency. The resulting well-protected LAB can be applied in probiotics foods. (c) 2016 Society of Chemical Industry. PMID- 26804615 TI - Nickel-Catalyzed Activation of Acyl C-O Bonds of Methyl Esters. AB - We report the first catalytic method for activating the acyl C-O bonds of methyl esters through an oxidative-addition process. The oxidative-addition adducts, formed using nickel catalysis, undergo in situ trapping to provide anilide products. DFT calculations are used to support the proposed reaction mechanism, to understand why decarbonylation does not occur competitively, and to elucidate the beneficial role of the substrate structure and the Al(OtBu)3 additive on the kinetics and thermodynamics of the reaction. PMID- 26804616 TI - Protein source and choice of anticoagulant decisively affect nanoparticle protein corona and cellular uptake. AB - Protein adsorption on nanoparticles has been a focus of the field of nanocarrier research in the past few years and more and more papers are dealing with increasingly detailed lists of proteins adsorbed to a plethora of nanocarriers. While there is an urgent need to understand the influence of this protein corona on nanocarriers' interactions with cells the strong impact of the protein source on corona formation and the consequence for interaction with different cell types are factors that are regularly neglected, but should be taken into account for a meaningful analysis. In this study, the importance of the choice of protein source used for in vitro protein corona analysis is concisely investigated. Major and decisive differences in cellular uptake of a polystyrene nanoparticle incubated in fetal bovine serum, human serum, human citrate and heparin plasma are reported. Furthermore, the protein compositions are determined for coronas formed in the respective incubation media. A strong influence of heparin, which is used as an anticoagulant for plasma generation, on cell interaction is demonstrated. While heparin enhances the uptake into macrophages, it prevents internalization into HeLa cells. Taken together we can give the recommendation that human plasma anticoagulated with citrate seems to give the most relevant results for in vitro studies of nanoparticle uptake. PMID- 26804618 TI - Comparison of different optical coherence tomography devices for diagnosis of non melanoma skin cancer. AB - PURPOSE: To compare the diagnostic imaging ability of three different optical coherence tomography (OCT) devices in non-melanoma skin cancer (NMSC). METHODS: Thirty actinic keratoses (AKs) and 27 basal cell carcinomas (BCCs) of 29 patients were examined with three different OCT devices, VivoSight(r) , Callisto(r) and Skintell(r) . RESULTS: Complete data sets were available for 16 BCCs and 10 AKs of 18 patients. All OCT devices were able to discriminate BCCs and AKs significantly from perilesional normal skin due to lower signal intensities as well as a thicker stratum corneum and epidermis in AKs. A significant decrease in the signal intensity and thickness of all skin layers was noted with Skintell(r) in contrast to VivoSight(r) and Callisto(r) . OCT comparisons revealed only slight differences between VivoSight(r) and Callisto(r) . Regarding BCC tumor thickness VivoSight(r) and Callisto(r) correlated well, histology did not correlate with the three OCT devices, whereas Skintell(r) showed no correlation with VivoSight(r) , Callisto(r) or histology. CONCLUSION: All tested OCT devices could identify BCCs and AKs objectively through standardized measurement of signal intensity and skin layer thickness. Due to their technical specifications (resolution, penetration depth), each of the OCT systems offers additional and special information on NMSC. PMID- 26804619 TI - Identification and validation of novel low-tiller number QTL in common wheat. AB - KEY MESSAGE: SNP-based QTL mapping provided useful information for novel loci that can be used in breeding programs to control tillering and improve yield in wheat via marker-assisted selection. Tillering is one of the most important agronomic traits affecting biomass and grain yield potential in wheat. Wheat lines with very limited tillering capacity are more productive than free tillering lines under severe drought conditions. In this study, three recombinant inbred line (RIL) populations were generated and used, having H461, a low tillering genotype, as a common parent. A linkage map containing 7808 single nucleotide polymorphism loci was constructed on the basis of H461/CN16 RIL population. Three QTL controlling low tillering were identified on Chromosome (Chr.) 2D (Qltn.sicau-2D), Chr. 2B (Qltn.sicau-2B), and Chr. 5A (Qltn.sicau-5A). Qltn.sicau-2D, Qltn.sicau-2B, and Qltn.sicau-5A explained up to 19.1, 14.6, and 9.6 % of the phenotypic variance, respectively. Comparing with previous findings, Qltn.sicau-2D and Qltn.sicau-2B should thus be novel tillering QTL. The effects of these QTL were further validated in two additional RIL populations. Significant effects of Qltn.sicau-2D were detected across all growth stages in different genetic backgrounds, making it an ideal target for breeding programs as well as for further characterization of the gene(s) underlying this locus. PMID- 26804623 TI - Synthesis and Biological Assessment of Racemic Benzochromenopyrimidinimines as Antioxidant, Cholinesterase, and Abeta1-42 Aggregation Inhibitors for Alzheimer's Disease Therapy. AB - Given the complex nature of Alzheimer's disease (AD), compounds that are able to simultaneously address two or more AD-associated targets show greater promise for development into drugs for AD therapy. Herein we report an efficient two-step synthesis and biological evaluation of new racemic benzochromene derivatives as antioxidants, inhibitors of cholinesterase and beta-amyloid (Abeta1-42 ) aggregation. Based on the results of the primary screening, we identified 15-(3 methoxyphenyl)-9,11,12,15-tetrahydro-10H,14H-benzo[5,6]chromeno[2,3-d]pyrido[1,2 a]pyrimidin-14-imine (3 e) and 16-(3-methoxyphenyl)-9,10,11,12,13,16-hexahydro 15H-benzo[5',6']chromeno[2',3':4,5]pyrimido[1,2-a]azepin-15-imine (3 f) as new potential multitarget-directed ligands for AD therapy. Further in-depth biological analysis showed that compound 3 f is a good human acetylcholinesterase inhibitor [IC50 =(0.36+/-0.02) MUm], has strong antioxidant activity (3.61 MUmol Trolox equivalents), and moderate Abeta1-42 antiaggregating power (40.3 %). PMID- 26804625 TI - Effect of Polymer Binders on UV-Responsive Organic Thin-Film Phototransistors with Benzothienobenzothiophene Semiconductor. AB - The influence of polymer binders on the UV response of organic thin-film phototransistors (OTF-PTs) is reported. The active channel of the OTF-PTs was fabricated by blending a UV responsive 2,7-dipenty-[1]benzothieno[2,3 b][1]benzothiophene (C5-BTBT) as small molecule semiconductor and a branched unsaturated polyester (B-upe) as dielectric binder (ratio 1:1). To understand the influence of the polymer composition on the photoelectrical properties and UV response of C5-BTBT, control blends were prepared using common dielectric polymers, namely, poly(vinyl acetate) (PVAc), polycarbonate (PC), and polystyrene (PS), for comparison. Thin-film morphology and nanostructure of the C5 BTBT/polymer blends were investigated by means of optical and atomic force microscopy, and powder X-ray diffraction, respectively. Electrical and photoelectrical characteristics of the studied OTF-PTs were evaluated in the dark and under UV illumination with a constant light intensity (P = 3 mW cm(-2), lambda = 365 nm), respectively, using two- and three-terminal I-V measurements. Results revealed that the purposely chosen B-upe polymer binder strongly affected the UV response of OTF-PTs. A photocurrent increase of more than 5 orders of magnitude in the subthreshold region was observed with a responsivity as high as 9.7 AW(-1), at VG = 0 V. The photocurrent increase and dramatic shift of VTh,average (~86 V) were justified by the high number of photogenerated charge carriers upon the high trap density in bulk 8.0 * 10(12) cm(-2) eV(-1) generated by highly dispersed C5-BTBT in B-upe binder. Compared with other devices, the B upe OTF-PTs had the fastest UV response times (taur1/taur2 = 0.5/6.0) reaching the highest saturated photocurrent (>10(6)), at VG = -5 V and VSD = -60 V. The enhanced UV sensing properties of B-upe based OTF-PTs were attributed to a self induced thin-film morphology. The enlarged interface facilitated the electron withdrawing/donating functional groups in the polymer chains in influencing the photocharge separation, trapping and recombination. PMID- 26804624 TI - A small molecule inhibitor of tropomyosin dissociates actin binding from tropomyosin-directed regulation of actin dynamics. AB - The tropomyosin family of proteins form end-to-end polymers along the actin filament. Tumour cells rely on specific tropomyosin-containing actin filament populations for growth and survival. To dissect out the role of tropomyosin in actin filament regulation we use the small molecule TR100 directed against the C terminus of the tropomyosin isoform Tpm3.1. TR100 nullifies the effect of Tpm3.1 on actin depolymerisation but surprisingly Tpm3.1 retains the capacity to bind F actin in a cooperative manner. In vivo analysis also confirms that, in the presence of TR100, fluorescently tagged Tpm3.1 recovers normally into stress fibers. Assembling end-to-end along the actin filament is thereby not sufficient for tropomyosin to fulfil its function. Rather, regulation of F-actin stability by tropomyosin requires fidelity of information communicated at the barbed end of the actin filament. This distinction has significant implications for perturbing tropomyosin-dependent actin filament function in the context of anti-cancer drug development. PMID- 26804626 TI - Covalent Immobilization of a Molecular Catalyst on Cu2O Photocathodes for CO2 Reduction. AB - Sunlight-driven CO2 reduction is a promising way to close the anthropogenic carbon cycle. Integrating light harvester and electrocatalyst functions into a single photoelectrode, which converts solar energy and CO2 directly into reduced carbon species, is under extensive investigation. The immobilization of rhenium containing CO2 reduction catalysts on the surface of a protected Cu2O-based photocathode allows for the design of a photofunctional unit combining the advantages of molecular catalysts with inorganic photoabsorbers. To achieve large current densities, a nanostructured TiO2 scaffold, processed at low temperature, was deposited on the surface of protected Cu2O photocathodes. This led to a 40 fold enhancement of the catalytic photocurrent as compared to planar devices, resulting in the sunlight-driven evolution of CO at large current densities and with high selectivity. Potentiodynamic and spectroelectrochemical measurements point toward a similar mechanism for the catalyst in the bound and unbound form, whereas no significant production of CO was observed from the scaffold in the absence of a molecular catalyst. PMID- 26804629 TI - The coracoclavicular joint. A systematic review and meta-analysis. AB - The coracoclavicular joint (CCJ) is considered as a rare articulation in humans. Though rarely it could be symptomatic, its presence should be acknowledged by physicians. The aim of this systematic review is to conduct an evidence synthesis on the prevalence of this condition in different ethnic populations. Thirty nine studies including 51 sub-studies met the inclusion criteria. The meta-analytical results showed true prevalence values of ?5%, ?7% and ?2.7% from skeletal, cadaveric and radiological studies, respectively. The bilateral occurrence of CCJ was found to be approximately the half of the crude prevalence and that in all study types. European populations showed the least frequency whereas the Eastern Asian and Native American populations showed the highest values in skeletal/cadaveric studies. European, modern American, Native American and modern South American populations showed the least CCJ occurrence rates in radiological studies. The Chinese population stood out from all other ancestries with a prevalence of 21%, followed by the Southeast Asians with a frequency of 6%. No association was found with variables such as sex or side. This evidence-based anatomical and anthropological review shed the light on the rare and poorly investigated CCJ. It yielded more accurate overall and ancestry-based frequencies from skeletal, cadaveric and radiological studies. PMID- 26804630 TI - Airway epithelial repair in health and disease: Orchestrator or simply a player? AB - Epithelial cells represent the most important surface of contact in the body and form the first line of defence of the body to external environment. Consequently, epithelia have numerous roles in order to maintain a homeostatic defence barrier. Although the epithelium has been extensively studied over several decades, it remains the focus of new research, indicating a lack of understanding that continues to exist around these cells in specific disease settings. Importantly, evidence is emerging that airway epithelial cells in particular have varied complex functions rather than simple passive roles. One area of current interest is its role following injury. In particular, the epithelial-specific cellular mechanisms regulating their migration during wound repair remain poorly understood and remain an area that requires much needed investigation. A better understanding of the physiological, cellular and molecular wound repair mechanisms could assist in elucidating pathological processes that contribute to airway epithelial pathology. This review attempts to highlight migration-specific and cell-extracellular matrix (ECM) aspects of repair used by epithelial cells under normal and disease settings, in the context of human airways. PMID- 26804631 TI - [Formula: see text]Introducing a forced-choice recognition task to the California Verbal Learning Test - Children's Version. AB - The importance of performance validity tests (PVTs) is increasingly recognized in pediatric neuropsychology. To date, research has focused on investigating whether PVTs designed for adults function similarly in children. The downward extension of adult cutoffs is counter-intuitive considering the robust effect of age related changes in basic cognitive skills in children and adolescents. The purpose of this study was to examine the signal detection properties of a forced choice recognition trial (FCR-C) for the California Verbal Learning Test - Children's Version. A total of 72 children aged 6-15 years (M = 11.1 , SD = 2.6) completed the FCR-C as part of a larger neuropsychological assessment battery. Cross-validation analyses revealed that the FCR-C had good signal detection performance against reference PVTs. The first level of failure (<=14/15) produced the best combination of overall sensitivity (.31) and specificity (.87). A more conservative FCR-C cutoff (<=13) resulted in a predictable trade-off between sensitivity (.15) and specificity (.94), but also a net loss in discriminant power. Lowering the cutoff to <=12 resulted in a slight improvement in specificity (.97) but further deterioration in sensitivity (.14). These preliminary findings suggest that the FCR-C has the potential to become the newest addition to a growing arsenal of pediatric PVTs. PMID- 26804633 TI - High early life mortality in free-ranging dogs is largely influenced by humans. AB - Free-ranging dogs are a ubiquitous part of human habitations in many developing countries, leading a life of scavengers dependent on human wastes for survival. The effective management of free-ranging dogs calls for understanding of their population dynamics. Life expectancy at birth and early life mortality are important factors that shape life-histories of mammals. We carried out a five year-long census based study in seven locations of West Bengal, India, to understand the pattern of population growth and factors affecting early life mortality in free-ranging dogs. We observed high rates of mortality, with only ~19% of the 364 pups from 95 observed litters surviving till the reproductive age; 63% of total mortality being human influenced. While living near people increases resource availability for dogs, it also has deep adverse impacts on their population growth, making the dog-human relationship on streets highly complex. PMID- 26804634 TI - Effect of glycerol concentrations on the mechanical properties of additive manufactured porous calcium polyphosphate structures for bone substitute applications. AB - This article addresses the effects of glycerol (GLY) concentrations on the mechanical properties of calcium polyphosphate (CPP) bone substitute structures manufactured using binder jetting additive manufacturing. To achieve this goal, nine types of water-based binder solutions were prepared with 10, 12.5, and 15 wt % GLY liquid-binding agent, mixed, respectively, with 0, 0.75, and 1.5 wt % ethylene glycol diacetate (EGD) flow enhancer. The print quality of each of the solutions was established quantitatively using an image processing algorithm. The print quality analysis narrowed down the solutions to three batches containing 1.5 wt % EGD and variable amount of GLY. These solutions were used to manufacture porous CPP bone substitute samples, which were characterized physically to determine shrinkage, porosity, microstructure, and compression strength. The 12.5 wt % GLY, 1.5 wt % EGD solution resulted in the highest mechanical strength after sintering (34.6 +/- 5.8 MPa), illustrating similar mechanical properties when compared to previous studies (33.9 +/- 6.3 MPa) of additively manufactured CPP bone substitutes using a commercially available binder. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 828-835, 2017. PMID- 26804635 TI - [Gynecologie Sans Frontieres association with migrant women in the North of France]. PMID- 26804636 TI - Myopes experience greater contrast adaptation during reading. AB - In this study, we investigated whether reading influences contrast adaptation differently in young adult emmetropic and myopic participants at the spatial frequencies created by text rows and character strokes. Pre-adaptation contrast sensitivity was measured for test gratings with spatial frequencies of 1cdeg(-1) and 4cdeg(-1), presented horizontally and vertically. Participants then adapted to reading text corresponding to the horizontal "row frequency" of text (1cdeg( 1)), and vertical "stroke frequency" of the characters (4cdeg(-1)) for 180s. Following this, post-adaptation contrast sensitivity was measured. Twenty young adults (10 myopes, 10 emmetropes) optimally corrected for the viewing distance participated. There was a significant reduction in logCS post-text adaptation (relative to pre-adaptation logCS) at the row frequency (1cdeg(-1) horizontal) but not at the stroke frequency (4cdeg(-1) vertical). logCS changes due to adaptation at 1cdeg(-1) horizontal were significant in both emmetropes and myopes. Comparing the two refractive groups, myopic participants showed significantly greater adaptation compared to emmetropic participants. Reading text on a screen induces contrast adaptation in young adult observers. Myopic participants were found to exhibit greater contrast adaptation than emmetropes at the spatial frequency corresponding to the text row frequency. No contrast adaptation was observed at the text stroke frequency in either participant group. The greater contrast adaptation experienced by myopes after reading warrants further investigation to better understand the relationship between near work and myopia development. PMID- 26804637 TI - Longitudinal Brain Changes Associated with Prophylactic Cranial Irradiation in Lung Cancer. AB - INTRODUCTION: The toxic effects of prophylactic cranial irradiation (PCI) and platinum-based chemotherapy on cognition in the lung cancer population have not yet been well established. In the present study we examined the longitudinal neuropsychological and brain structural changes observed in patients with lung cancer who were undergoing these treatments. METHODS: Twenty-two patients with small cell lung cancer (SCLC) who underwent platinum-based chemotherapy and PCI were compared with two control groups: an age- and education-matched group of healthy controls (n = 21) and a group of patients with non-SCLC (NSCLC, n = 13) who underwent platinum-based chemotherapy. All groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging: T1-weighted and diffusion tensor imaging at baseline (before PCI for SCLC and chemotherapy for NSCLC) and at 3 months after treatment. T1 voxel-based morphometry and tract-based spatial statistics were used to analyze microstructural changes in gray matter (GM) and white matter (WM). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core Questionnaire was also completed. RESULTS: Patients with SCLC exhibited cognitive deterioration in verbal fluency over time. Structural magnetic resonance imaging showed decreases in GM at 3 months in the right subcortical regions, bilateral insular cortex, and superior temporal gyrus in patients with SCLC compared with both control groups. Additionally, patients with SCLC showed decreases in GM over time in the aforementioned regions plus in the right parahippocampal gyrus and hippocampus, together with changes in the WM microstructure of the entire corpus callosum. These changes had a limited impact on responses to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire, however. Patients with NSCLC showed no cognitive or brain structural differences after chemotherapy. CONCLUSIONS: This longitudinal study documents moderate neuropsychological deficits together with notable brain-specific structural changes (in GM and WM) in patients with SCLC after chemotherapy and PCI, suggesting that chemotherapy and especially PCI are associated with the development of cognitive and structural brain toxic effects. PMID- 26804638 TI - Synergistic Activation upon MET and ALK Coamplification Sustains Targeted Therapy in Sarcomatoid Carcinoma, a Deadly Subtype of Lung Cancer. AB - INTRODUCTION: Genetic alterations suitable for targeted therapy are poorly known issues in pulmonary sarcomatoid carcinoma (PSC), an uncommon and life-threatening family of non-small cell lung cancers. METHODS: Ninety-eight PSCs were assessed for MNNG HOS Transforming gene (MET) and anaplastic lymphoma receptor tyrosine kinase gene (ALK) status by fluorescence in situ hybridization (FISH) and for relevant protein expression by immunohistochemical analysis, also taking advantage of phosphorylated (p-) antibodies. Moreover, levels of ALK and MET mRNA were also determined by real-time polymerase chain reaction and Western blot analysis for downstream activation pathways involving p-MET, p-protein kinase B, p-mitogen-activated protein kinase, p-SRC proto-oncogene tyrosine-protein kinase, and p-focal adhesion kinase (p-FAK). RESULTS: MET amplification was detected by FISH in 25 of 98 PSCs (25.6%) and ALK amplification (but not the relevant rearrangement) was found in 16 of 98 (16.3%), with all ALK-amplified tumors also showing MET amplification (p < 0.0001). Nine PSCs, however, showed MET amplification without any ALK gene alteration. ALK protein expression was always lacking, whereas MET and p-MET were confined to the relevant amplified tumors only. Increased levels of ALK and MET mRNA were detectable in tumors with no direct relationship between mRNA content, protein expression, or alterations detected by FISH. Western blot assays showed complete activation of downstream signal pathways up to p-SRC proto-oncogene tyrosine-protein kinase, and p-focal adhesion kinase recruitment in MET and ALK-coamplified tumors only, whereas isolated MET amplification, MET and ALK borderline amplification (5%-10% of tumor cells with >=15 copies of the relevant gene), or negative tumors showing eusomy or chromosome polysomy were confined to p-mitogen-activated protein kinase, p protein kinase B, and/or p-MET activation. Multivariate survival analysis pushed a higher percentage of MET altered cells or a higher value of MET copy gain per cell to marginally emerge for overall survival (p = 0.140) and disease-free survival (p = 0.060), respectively. CONCLUSIONS: ALK and MET seemed to act as synergistic, nonrandom coactivators of downstream signal when coamplified in a subset of patients with PSC, thus likely suggesting a combined mechanism of oncogene addiction. These alterations could be a suitable target for therapy based on specific inhibitors. PMID- 26804639 TI - Evaluation of the Pharmacokinetics of Single- and Multiple-dose Buprenorphine Buccal Film in Healthy Volunteers. AB - PURPOSE: Buprenorphine, a partial MU-receptor agonist, is approved for the management of moderate to severe pain, but it has low oral bioavailability. Two open-label studies were performed to determine the pharmacokinetic profile of buprenorphine from buccal film formulations of buprenorphine. METHODS: Both studies enrolled healthy volunteers, aged 18 to 55 years, who received concurrent oral naltrexone to reduce adverse events (AEs); subjects with a history or evidence of substance abuse or current use of any product affecting cytochrome P450 3A4 activity were excluded. The first study (n = 25) was a 5-period crossover trial with 4 single doses (75 and 300 and 300 and 1200 MUg) of 2 formulations (F14 and F24) of buccal buprenorphine (BBUP) and a 300-MUg intravenous dose of buprenorphine with a 7-day washout between periods. In the second study, each subject (n = 10) received 6 doses of 4 BBUP strengths (60, 120, 180, and 240 MUg BID) in a dose-escalation design. Plasma concentrations of buprenorphine and norbuprenorphine were assayed, and pharmacokinetics were summarized with descriptive statistics and analyzed by using a linear mixed effects model (single-dose study). AEs were recorded. FINDINGS: In the single dose study, the 2 formulations exhibited comparable bioavailability of 46% to 51% that was independent of dose, with a single buprenorphine peak concentration from each BBUP dose occurring at 2.5 to 3 hours. The mean buprenorphine Cmax across the doses ranged from 0.17 ng/mL for the 75-ug dose to 1.43 ng/mL for the 1200-ug dose. AUC0-infinity, AUC0-last, and Cmax were proportional to the dose of BBUP administered. Cmax of norbuprenorphine after BBUP administration was approximately one tenth that of buprenorphine Cmax. In the multiple-dose study, steady state was reached within 3 days of BID dosing. There was a linear increase in exposure across the dose range from 60 to 240 MUg BID. Treatment-emergent AEs in both studies were consistent with those reported with opiate administration to healthy volunteers. IMPLICATIONS: The absolute bioavailability of BBUP was 46% to 51% across a 16-fold dose range, with dose-proportional increases in systemic exposure. Apparent steady-state conditions occurred within 3 days of dosing. These pharmacokinetic results suggest that therapeutic buprenorphine plasma concentrations can be obtained with BBUP across a wide dose range in a shorter time than other (eg, transdermal) dosage forms. PMID- 26804640 TI - Pharmacokinetic and Pharmacodynamic Properties of Cinacalcet (KRN1493) in Chinese Healthy Volunteers: A Randomized, Open-label, Single Ascending-dose and Multiple dose, Parallel-group Study. AB - PURPOSE: The aim of this study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) properties and safety of single and multiple doses of cinacalcet in Chinese healthy volunteers (HVs) for the purposes of a New Drug Application package for the Chinese Food and Drug Administration. METHODS: In this randomized, open-label, single ascending-dose and multiple-dose, parallel group study, 42 Chinese HVs were randomized to receive a single oral dose of 25, 50, or 100 mg of cinacalcet and multiple doses of 50 mg of cinacalcet once daily for 7 days. Plasma cinacalcet concentrations were analyzed by HPLC-MS/MS. The PK parameters were assessed with noncompartmental analysis. Plasma intact parathyroid hormone, serum calcium, and phosphorus concentrations were measured for PD evaluation. The safety profile was also assessed. Adverse events (AEs) were noted during the study. FINDINGS: Of the 42 randomized HVs, 41 completed the study per protocol; 1 prematurely discontinued the study because of AEs. Cinacalcet has nonlinear PK properties over a dose range of 25 to 100 mg after a single dose. Mean (SD) Cmax values were 7.68 (4.25), 17 (6.33), and 31.3 (16.42) ng/mL with single doses of 25, 50, and 100 mg of cinacalcet, respectively. Mean (SD) AUC0- last values were 58.4 (25.38), 187 (70.7), and 367 (180.03) hr?ng/mL with single doses of 25, 50, and 100 mg of cinacalcet, respectively. Steady state was attained within 7 doses of successive daily administration of 50 mg of cinacalcet. At steady state, the mean (SD) Cmax and AUC0-last values were 20.6 (9.63) ng/mL and 297 (146.15) ng?h/mL. The accumulation ratios of Cmax and AUC (AUCtau/AUC0-24) were 1.21 and 1.32. Plasma intact parathyroid hormone and serum calcium concentrations had similar patterns, both decreased after administration of cinacalcet, whether after single dose or multiple doses. A total of 52 AEs were reported in 20 HVs (47.6%). The most frequently reported AEs after single dose and multiple-dose cinacalcet administration were hypocalcemia, numbness, dizziness, and muscle soreness. No serious AEs were reported. IMPLICATIONS: Cinacalcet was well tolerated and effective after administration of a single oral dose up to 100 mg and multiple doses of 50 mg of cinacalcet once daily for 7 days. Cinacalcet has nonlinear PK properties over a dose range of 25 to 100 mg after a single dose. PK profiles after multiple doses were similar to those after a single dose with no accumulation. Cinacalcet had similar PK and safety profiles between Chinese and Western HVs at the same dose levels. PMID- 26804642 TI - Towards developing a general framework for modelling vertical migration in zooplankton. AB - Diel vertical migration (DVM) of zooplankton is a widespread phenomenon in both oceans and lakes, and is generally considered to be the largest synchronized movement of biomass on Earth. Most existing mathematical models of DVM are based on the assumption that animals maximize a certain criterion such as the expected reproductive value, the venturous revenue, the ratio of energy gain/mortality or some predator avoidance function when choosing their instantaneous depth. The major shortcoming of this general point of view is that the predicted DVM may be strongly affected by a subjective choice of a particular optimization criterion. Here we argue that the optimal strategy of DVM can be unambiguously obtained as an outcome of selection in the underlying equations of genotype/traits frequency dynamics. Using this general paradigm, we explore the optimal strategy for the migration across different depths by zooplankton grazers throughout the day. To illustrate our ideas we consider four generic DVM models, each making different assumptions on the population dynamics of zooplankton, and demonstrate that in each model we need to maximize a particular functional to find the optimal strategy. Surprisingly, patterns of DVM obtained for different models greatly differ in terms of their parameters dependence. We then show that the infinite dimensional trait space of different zooplankton trajectories can be projected onto a low dimensional space of generalized parameters and the genotype evolution dynamics can be easily followed using this low-dimensional space. Using this space of generalized parameters we explore the influence of mutagenesis on evolution of DVM, and we show that strong mutagenesis allows the coexistence of an infinitely large number of strategies whereas for weak mutagenesis the selection results in the extinction of most strategies, with the surviving strategies all staying close to the optimal strategy in the corresponding mutagenesis-free system. PMID- 26804641 TI - Factors Contributing to the Clinical Effectiveness of the DPP-4 Inhibitor Sitagliptin in Patients With Type 2 Diabetes. AB - PURPOSE: Treatment with dipeptidyl peptidase 4 (DPP-4) inhibitors may have responders or nonresponders. However, agreement on the effects of patient background and/or contributory factors that have a negative effect on the efficacy of DPP-4 inhibitors is lacking. The aim of the present study was to investigate the effect of resistance factors on the clinical efficacy of sitagliptin (SITA) for patients with type 2 diabetes. METHODS: We performed a retrospective study based on the medical records of patients who were treated with SITA alone (SITA-A; n = 16), a combination of a sulfonylurea (SU) without a change in dose and add-on SITA (SU + SITA; n = 29), SITA alone after the discontinuation of premedication with antidiabetic agents (SITA-AD; n = 18), or a combination of an SU with a dose reduction and SITA (L-SU + SITA; n = 17). Multivariate logistic regression analysis was employed to estimate the influence of resistance factors on hemoglobin (Hb) A1c lowering by SITA treatment for 3 months. FINDINGS: The HbA1c levels were significantly lower after 3-month treatment with SITA-A (6.3% [0.2%]), SU + SITA (7.1% [0.2%]), and L-SU + SITA (6.6% [0.2%]), but not with SITA-AD (6.3% [0.2%]), than baseline levels before treatment. Multivariate logistic regression analysis established that a decreased efficacy of SITA was markedly related to baseline HbA1c levels of >=7.5% and dyslipidemia. IMPLICATIONS: These results suggest that checking for the presence or absence of resistance factors, including elevated HbA1c levels and dyslipidemia, may contribute to the appropriate usage of SITA. PMID- 26804643 TI - Pharmacophore modeling, 3D-QSAR and docking study of 2-phenylpyrimidine analogues as selective PDE4B inhibitors. AB - Pharmacophore modeling, molecular docking, and molecular dynamics (MD) simulation studies have been performed, to explore the putative binding modes of 2 phenylpyrimidine series as PDE4B selective inhibitors. A five point pharmacophore model was developed using 87 molecules having pIC50 ranging from 8.52 to 5.07. The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a high correlation coefficient (R(2)=0.918), cross validation coefficient (Q(2)=0.852), and F value (175) at 4 component PLS factor. The external validation indicated that our QSAR model possessed high predictive power (R(2)=0.70). The generated model was further validated by enrichment studies using the decoy test. To evaluate the effectiveness of docking protocol in flexible docking, we have selected crystallographic bound compound to validate our docking procedure as evident from root mean square deviation. A 10ns molecular dynamics simulation confirmed the docking results of both stability of the 1XMU-ligand complex and the presumed active conformation. Further, similar orientation was observed between the superposition of the conformations of 85 after MD simulation and best XP-docking pose; MD simulation and 3D-QSAR pose; best XP-docking and 3D-QSAR poses. Outcomes of the present study provide insight in designing novel molecules with better PDE4B selective inhibitory activity. PMID- 26804644 TI - A novel conformational B-cell epitope prediction method based on mimotope and patch analysis. AB - A B-cell epitope is a group of residues on the surface of an antigen that stimulates humoral immune responses. Identifying B-cell epitopes is important for effective vaccine design. Predicting epitopes by experimental methods is expensive in terms of time, cost and effort; therefore, computational methods that have a low cost and high speed are widely used to predict B-cell epitopes. Recently, epitope prediction based on random peptide library screening has been viewed as a promising method. Some novel software and web-based servers have been proposed that have succeeded in some test cases. Herein, we propose a novel epitope prediction method based on amino acid pairs and patch analysis. The method first divides antigen surfaces into overlapping patches based on both radius (R) and number (N), then predict epitopes based on Amino Acid Pairs (AAPs) from mimotopes and the surface patch. The proposed method yields a mean sensitivity of 0.53, specificity of 0.77, ACC of 0.75 and F-measure of 0.45 for 39 test cases. Compared with mimotope-based methods, patch-based methods and two other prediction methods, the sensitivity of the new method offers a certain improvement. Our findings demonstrate that this proposed method was successful for patch and AAPs analysis and allowed for conformational B-cell epitope prediction. PMID- 26804645 TI - A network model for Ebola spreading. AB - The availability of accurate models for the spreading of infectious diseases has opened a new era in management and containment of epidemics. Models are extensively used to plan for and execute vaccination campaigns, to evaluate the risk of international spreadings and the feasibility of travel bans, and to inform prophylaxis campaigns. Even when no specific therapeutical protocol is available, as for the Ebola Virus Disease (EVD), models of epidemic spreading can provide useful insight to steer interventions in the field and to forecast the trend of the epidemic. Here, we propose a novel mathematical model to describe EVD spreading based on activity driven networks (ADNs). Our approach overcomes the simplifying assumption of homogeneous mixing, which is central to most of the mathematically tractable models of EVD spreading. In our ADN-based model, each individual is not bound to contact every other, and its network of contacts varies in time as a function of an activity potential. Our model contemplates the possibility of non-ideal and time-varying intervention policies, which are critical to accurately describe EVD spreading in afflicted countries. The model is calibrated from field data of the 2014 April-to-December spreading in Liberia. We use the model as a predictive tool, to emulate the dynamics of EVD in Liberia and offer a one-year projection, until December 2015. Our predictions agree with the current vision expressed by professionals in the field, who consider EVD in Liberia at its final stage. The model is also used to perform a what-if analysis to assess the efficacy of timely intervention policies. In particular, we show that an earlier application of the same intervention policy would have greatly reduced the number of EVD cases, the duration of the outbreak, and the infrastructures needed for the implementation of the intervention. PMID- 26804647 TI - Spinal seeding of choroid plexus papilloma. PMID- 26804646 TI - Efficacy and safety of an adjunctive mGlu2 receptor positive allosteric modulator to a SSRI/SNRI in anxious depression. AB - This phase 2a, randomized, multicenter, double-blind, proof-of-concept study was designed to evaluate, efficacy, safety and tolerability of JNJ-40411813/ADX71149, a novel metabotropic glutamate 2 receptor positive allosteric modulator as an adjunctive treatment for major depressive disorder (MDD) with significant anxiety symptoms. Eligible patients (18-64 years) had a DSM-IV diagnosis of MDD, Hamilton Depression Rating Scale-17 (HDRS17) score of >= 18, HDRS17 anxiety/somatization factor score of >= 7, and an insufficient response to current treatment with a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor. The doubly-randomized, 8-week double-blind treatment phase was comprised of two 4-week periods, from which a combined test statistic was generated, with pre-determined weights assigned to each of the 2 treatment periods. Period 1: patients (n=121) were randomly assigned (1:1) to JNJ-40411813 (n=62; 50mg to 150 mg b.i.d, flexibly dosed) or placebo (n=59); Period 2: placebo treated patients (n=22) who continued to meet entry severity criteria were re randomized (1:1) to JNJ-40411813 or placebo, while other patients underwent sham re-randomization and continued on their same treatment. Of 121 randomized patients, 100 patients (82.6%) were completers. No efficacy signal was detected on the primary endpoint, the 6-item Hamilton Anxiety Subscale (HAM-A6, p=0.51). Efficacy signals (based on prespecified 1-sided p<0.20) were evident on several secondary outcome measures of both depression (HDRS17 total score, 6-item subscale of HDRS17 assessing core depressive symptoms [HAM-D6], and Inventory of Depressive Symptomatology [IDS-C30]) and anxiety (HDRS17 anxiety/somatization factor, IDS-C30 anxiety subscale). Although well-tolerated, the results do not suggest efficacy for JNJ-40411813 as an adjunctive treatment for patients with MDD with significant anxious symptoms in the dose range studied. PMID- 26804648 TI - A novel C-type lectin is involved in the innate immunity of Macrobrachium nipponense. AB - C-type lectins (CTLs) play important roles in invertebrate innate immunity by recognizing and eliminating pathogens. In the present study, a low-density lipoprotein receptor class A (LDLa) domain-containing CTL was identified from the oriental river prawn Macrobrachium nipponense, designated as MnCTLDcp1. The full length cDNA of MnCTLDcp1 was composed of 1462 bp, with a 999-bp ORF encoding a 332-aa protein. An LDLa and a single C-type lectin-like domain (CTLD) were found. The mRNA transcripts of MnCTLDcp1 was expressed the highest in heart. After the prawns were challenged by Aeromonas hydrophila and Staphylococcus aureus, the expression level of MnCTLDcp1 in heart and hemocytes were all significantly up regulated. Sugar binding assay revealed that the MnCTLDcp1 could bind to the glycoconjugates of bacteria surface, such as LPS, PGN and they can compete with bacterial as competitors. The recombinant MnCTLDcp1 agglutinates Gram-positive (S. aureus and Bacillus subtilis) and Gram-negative bacteria (A. hydrophila, Vibrio parahaemolyticus, Escherichia coli and Pseudomonas aeruginosa) in the presence of calcium and also could bind to these bacteria. These results clearly suggested that MnCTLDcp1 functions as a pattern-recognition receptor involved in the innate immunity of M. nipponense. PMID- 26804649 TI - Transcriptome and analysis on the complement and coagulation cascades pathway of large yellow croaker (Larimichthys crocea) to ciliate ectoparasite Cryptocaryon irritans infection. AB - Large yellow croaker (Larimichthys crocea) is one of the most valuable marine fish in southern China. Given to the rapid development of aquaculture industry, the L. crocea was subjected to ciliate ectoparasite Cryptocaryon irritans. It therefore is indispensable and urgent to understand the mechanism of L. crocea host defense against C. irritans infection. In the present study, the extensively analysis at the transcriptome level for Cryptocaryoniasis in L. crocea was carried out. These results showed that 15,826,911, 16,462,921, and 15,625,433 paired-end clean reads were obtained from three cDNA libraries (A: 0 theronts/fish, B: 12,000 theronts/fish, and C: 24,000 theronts/fish) of the L. crocea immune-related tissues by Illumina paired-end sequencing technology. Totally, 30,509 unique transcript fragments (unigenes) were assembled, with an average length of 1715 bp. In B/A, C/A, and C/B pairwise comparison, 972, 900, and 1126 genes showed differential expression respectively. Differently expressed immune-related genes (DEIGs) were scrutinized, in B/A pairwise comparison, 48 genes showed differential expression, including 26 up-regulated genes and 22 down regulated genes in B; in C/A pairwise comparison, there were 39 DEIGs, including 7 up-regulated genes and 32 down-regulated genes in C; in C/B pairwise comparison, 40 genes showed differential expression, including 11 up-regulated genes and 29 down-regulated genes in C. There were 16 DEIGs enriched KEGG pathways, in which the complement and coagulation cascades pathway was the top most DEIGs enriched pathway (B:A = 42; C:A = 28; C:B = 42). The coagulation and fibrinolytic system was in a highly active state after infected by C. irritans with non-lethal concentration; the alternative complement pathway may play an important role in the early stages of C. irritans infection. These results demonstrated that low-concentration infection can significantly induce the immunological response in fishes, however, when fishes were in fatal conditions, the immunity was suppressed. PMID- 26804650 TI - Identification and functional characterization of three TLR signaling pathway genes in Cyclina sinensis. AB - Toll-like receptors (TLRs) are an ancient family of pattern recognition receptors that play a critical role in initiating and activating the innate immune system. In this study, we identified two TLR genes (CsTLR4 and CsTLR13) and the MyD88 (CsMyD88) gene using a transcriptome library from Cyclina sinensis. The sequence features and mRNA expression profiles of the genes were characterized, and their functions in the immune response were investigated to validate the TLR signaling pathway and its potential role in immune defense. The expression patterns of CsTLR4, CsTLR13 and CsMyD88 were detected in all the tissues examined from healthy clams and were primarily expressed in the hemocytes (P < 0.05), as shown by real-time PCR. Upon challenge with Vibrio anguillarum and Micrococcus luteus, they were significantly increased in hemocytes (P < 0.01), whereas only CsTLR13 and CsMyD88 were up-regulated (P < 0.01) by poly (I:C) challenge. In addition, the mRNA expression level of CsC-LYZ and CsAMP was down-regulated at 72 h (P < 0.01) after injection with CsMyD88 RNAi. These findings might be valuable for understanding the innate immune signaling pathways of C. sinensis and enabling future studies on host-pathogen interactions. PMID- 26804651 TI - Molecular characterization and expression of CD2 in Nile tilapia (Oreochromis niloticus) in response to Streptococcus agalactiae stimulus. AB - The cluster of differentiation 2 (CD2), functioning as a cell adhesion and costimulatory molecule, plays a crucial role in T-cell activation. In this paper, the CD2 gene of Nile tilapia, Oreochromis niloticus (designated as On-CD2) was cloned and its expression pattern under the stimulation of Streptococcus agalactiae was investigated. Sequence analysis showed On-CD2 protein consists of two extracellular Ig-like domains, a transmembrane region, and a long proline rich cytoplasmic tail, which is a hallmark of CD2, and several important structural characteristics required for T-cell activation were detected in the deduced amino acid sequence of On-CD2. In healthy tilapia, the On-CD2 transcripts were mainly detected in the head kidney, spleen, blood and thymus. Moreover, there was a clear time-dependent expression pattern of On-CD2 after immunized by formalin-inactivated S. agalactiae and the expression reached the highest level at 12 h in the brain and head kidney, 48 h in the spleen, and 72 h in the thymus, respectively. This is the first report on the expression of CD2 induced by bacteria vaccination in teleosts. These findings indicated that On-CD2 may play an important role in the immune response to intracellular bacteria in Nile tilapia. PMID- 26804652 TI - Phenotypic and clinical implications of variants in the dihydropyrimidine dehydrogenase gene. AB - Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of the pyrimidine bases uracil, thymine and the antineoplastic agent 5-fluorouracil. Genetic variations in the gene encoding DPD (DPYD) have emerged as predictive risk alleles for 5FU-associated toxicity. Here we report an in-depth analysis of genetic variants in DPYD and their consequences for DPD activity and pyrimidine metabolites in 100 Dutch healthy volunteers. 34 SNPs were detected in DPYD and 15 SNPs were associated with altered plasma concentrations of pyrimidine metabolites. DPD activity was significantly associated with the plasma concentrations of uracil, the presence of a specific DPYD mutation (c.1905+1G>A) and the combined presence of three risk variants in DPYD (c.1905+1G>A, c.1129-5923C>G, c.2846A>T), but not with an altered uracil/dihydrouracil (U/UH2) ratio. Various haplotypes were associated with different DPD activities (haplotype D3, a decreased DPD activity; haplotype F2, an increased DPD activity). Functional analysis of eight recombinant mutant DPD enzymes showed a reduced DPD activity, ranging from 35% to 84% of the wild-type enzyme. Analysis of a DPD homology model indicated that the structural effect of the novel p.G401R mutation is most likely minor. The clinical relevance of the p.D949V mutation was demonstrated in a cancer patient heterozygous for the c.2846A>T mutation and a novel nonsense mutation c.1681C>T (p.R561X), experiencing severe grade IV toxicity. Our studies showed that the endogenous levels of uracil and the U/UH2 ratio are poor predictors of an impaired DPD activity. Loading studies with uracil to identify patients with a DPD deficiency warrants further investigation. PMID- 26804653 TI - Evidence for synergistic action of transthyretin and IGF-I over the IGF-I receptor. AB - Transthyretin (TTR) has a neuroprotective role in the central nervous system (CNS) in Alzheimer's disease (AD) and cerebral ischemia. Increased levels of TTR and activated insulin-like growth factor I receptor (IGF-IR) are associated with reduced neurodegeneration in an AD mouse model. In the present study, we found that TTR and IGF-I have a synergistic effect on activation of one of the IGF-IR signaling pathways. Hippocampus of TTR null mice present decreased levels of phosphorylated IGF-IR and Akt when compared with TTR wild type littermate animals. Cell studies reveal the synergistic effect of TTR and IGF-I in promoting IGF-IR signaling even under glutamate induced toxicity. TTR:IGF-IR complexes are identified and a bio-layer interferometry assay demonstrated an interaction between TTR and IGF-IR with a KD ranging from 99 to 744nM. In summary, our results point to a new TTR role through the IGF-I axis, mediated through TTR-IGF IR interactions. PMID- 26804655 TI - "TO SEE OURSELVES AS OTHERS SEE US!": RELATIONS AMONG SELF-PERCEPTIONS, PEER PERCEPTIONS, AND EXPECTED PEER-PERCEPTIONS OF PERSONALITY. AB - The need for convergent validity in the measurement of personality variables and past failures to demonstrate such properties are briefly reviewed. Two apppoaches to the problem using several types of data obtained from various subject populations and employing alternative factor analytic methods and factor score estimation procedulres are described. The results indicate that convergent factor patterns and substantial convergence and discriminant validities among factor score estimates are obtainable when sufficient care is taken in the design and development of measure variables .of each type and when analysis methods appropriate for the problem are used. PMID- 26804654 TI - Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects. AB - Mitochondrial protein SURF1 is a specific assembly factor of cytochrome c oxidase (COX), but its function is poorly understood. SURF1 gene mutations cause a severe COX deficiency manifesting as the Leigh syndrome in humans, whereas in mice SURF1(-/-) knockout leads only to a mild COX defect. We used SURF1(-/-) mouse model for detailed analysis of disturbed COX assembly and COX ability to incorporate into respiratory supercomplexes (SCs) in different tissues and fibroblasts. Furthermore, we compared fibroblasts from SURF1(-/-) mouse and SURF1 patients to reveal interspecies differences in kinetics of COX biogenesis using 2D electrophoresis, immunodetection, arrest of mitochondrial proteosynthesis and pulse-chase metabolic labeling. The crucial differences observed are an accumulation of abundant COX1 assembly intermediates, low content of COX monomer and preferential recruitment of COX into I-III2-IVn SCs in SURF1 patient fibroblasts, whereas SURF1(-/-) mouse fibroblasts were characterized by low content of COX1 assembly intermediates and milder decrease in COX monomer, which appeared more stable. This pattern was even less pronounced in SURF1(-/-) mouse liver and brain. Both the control and SURF1(-/-) mice revealed only negligible formation of the I-III2-IVn SCs and marked tissue differences in the contents of COX dimer and III2-IV SCs, also less noticeable in liver and brain than in heart and muscle. Our studies support the view that COX assembly is much more dependent on SURF1 in humans than in mice. We also demonstrate markedly lower ability of mouse COX to form I-III2-IVn supercomplexes, pointing to tissue-specific and species-specific differences in COX biogenesis. PMID- 26804656 TI - CHARACTERISTIC RESPONSE MODES TO INTERPERSONAL SITUATIONS. AB - The study sought to identify (a) the main interpersonal situation-dimen- sions that evoke interpersonal responses, and (b) the main manifest reaction modes. An inventory consisting of 4 blocks of stimuli and 4 blocks of responses was developed. Responses were obtained to each set of stimuli from 258 women and 253 men. The correlations among stimuli and among responses to the stimuli were factored separately by block for each sex. Three factors were isolated within each simulus sector of control, hostility, support, and help-seeking. Three o r four factors were isolated within each response block. Since the findings were consistent across sex, they provide a useful scheme for conceptualizing interpersonal behavior. PMID- 26804657 TI - A FACTOR ANALYSIS OF BRAIN DAMAGE TESTS ADMINISTERED TO NORMAL SUBJECTS WITH FACTOR SCORE COMPARISONS ACROSS AGES. AB - This study investigated the factorial composition of brain damage tests selected on the basis of a comprehensive review of the test literature. The tests were administered to 100 normal persons between the ages of 16 and 70. Two analyses were performed. The first analysis concerned the determi- nation of the factorial composition of the brain damage tests selected. The results suggested that although the dimensionality of the brain damage test battery is relatively complex, the majority of the tests discriminate on the basis of a few dimensions, at least for normal persons. The second analysis involved the determination of factor scores for each individual on the twelve factors extracted in the 16-70 age group analysis. An analysis of the factor scores as a function of age indicated a significant difference for only two of the factors. This finding was discussed in terms of the possibility that certain of the tests would be psychometrically more efficient in differential diagnosis of brain damage in the older person. PMID- 26804658 TI - RELATIONSHIPS AMONG BEHAVIORAL, COGNITIVE-DEVELOPMENTAL, AND SELF REPORT MEASURES OF MORALITY AND PERSONALITY. AB - Seven behavioral resistance to temptation measures and seven cognitive and personality measures were obtained from 42 boys and 66 girls of junior high age. Principal components analysei were followed by orthogonal rotations according to varimax procedures, yielding five faotors for males and five for females. Three factors for males and one for females were formed by combinations of the temptation and personality-cognitive measures. PMID- 26804659 TI - THE USE AND UTILITY OF THE MONOTONE CRITERION IN MULTIDIMENSIONAL SCALING. AB - The monotone criterion as a multidimensional scaling technique is theoret- ically and empirically evaluated using the algorithms of Kruskal (MDSCAL) and Guttman Lingoes (SSA-1). Geometric configurations are used to test the recovery capabaty and other aspects of MDSCAL and SSA-1. In addition to theoretical shortcomings, the monotone criterion permits results which do not correspond to the shape of the input data. Because of its deficiencies, alterna- tive goodness-of-fit criteria are suggested in preference to the monotone criterion. PMID- 26804660 TI - SCIENTIFIC METHOD AND REPRODUCIBILITY OF RESULTS. AB - Statistical significance is not part of the scientific method. The three canons of reproducibility of an experiment: Data Matrix Homegeneity, Subject Generalizability, and Method Generalizability provide better guides to experimentation and theory development. As adjuncts to Scientific Method they provide a better basis for evaluation of statistical findings. PMID- 26804661 TI - THE SEARCH FOR CONFIGURAL RELATIONSHIPS IN PERSONALITY ASSESSMENT: THE DIAGNOSIS OF PSYCHOSIS vs. NEUROSIS FROM THE MMPI. AB - In 1956 Meehl predicted that the relationships between MMPI scores and the psychosis-neurosis diagnostic classification should be highly configural in character, and therefore that no linear combination of MMPI scores should be able to differentiate neurotic from psychotic patients as accurately as either experienced clinical psychologists or configural actuarial techniques. The present paper summarizes the findings from ten years of research on this question. While the search for configural actuarial procedures has led to a moderator variable, neither clinical experts, moderated regression analyses, profile typologies, the Perceptron algorithm, density estimation procedures, Bayesian techniques, nor sequential analyses-when cross-validated-have been-able to improve on a simple linear function. The implications of these negative findings for investigations of configural relationships with other problems are discussed. PMID- 26804662 TI - Nitric oxide synthase-dependent immune response against gram negative bacteria in a crustacean, Litopenaeus vannamei. AB - Nitric oxide (NO) is a short-lived radical generated by nitric oxide synthases (NOS). NO is involved in a variety of functions in invertebrates, including host defense. In previous studies, we isolated and sequenced for the first time the NOS gene from hemocytes of Panulirus argus, demonstrating the inducibility of this enzyme by lipopolysaccharide in vitro e in vivo. Hyperimmune serum was obtained from rabbits immunized with a P. argus -NOS fragment of 31 kDa produced in Escherichia coli, which specifically detected the recombinant polypeptide and the endogenous NOS from lobster hemocytes by western blotting and immunofluorescence. In the present work, we demonstrate that the hyperimmune serum obtained against P. argus NOS also recognizes Litopenaeus vannamei NOS in hemocytes by western blotting and immunofluorescence. Our data also show that while the hemolymph of L. vannamei has a strong antibacterial activity against the Gram negative bacteria Aeromonas hydrophila, the administration of the anti NOS serum reduce the natural bacterial clearance. These results strongly suggest that NOS is required for the shrimp immune defense toward Gram negative bacteria. Therefore, the monitoring of induction of NOS could be an important tool for testing immunity in shrimp farming. PMID- 26804663 TI - Editorial: Biosynthetic assembly lines themed issue. PMID- 26804664 TI - Thoracoscopy in the management of pediatric empyemas. AB - INTRODUCTION: Thoracoscopy is increasingly being used in the treatment of empyema. This study assesses feasibility, efficacy and safety in children. MATERIAL AND METHODS: Clinical files of patients who underwent primary thoracoscopy for empyema between 2006 and 2014 were reviewed. Demographic, clinical and surgical data were analyzed and a comparison between the period before (period1) and after (period2) the learning curve was performed. RESULTS: Ninety-one patients (53 males, 58%) were submitted to thoracoscopy at a median age of 4 years. There were 19 conversions to thoracotomy with a steady decrease of conversion rate until 2009 (period1) and no conversions thereafter (period2). There was no difference in any of the analyzed parameters between patients submitted to thoracoscopy alone and those requiring conversion in period1. Six cases (6.6%) needed redo-operation (five in period2) and thoracotomy was the elected approach in four. Necrotizing pneumonia was present in 60% of the reoperated cases; in other words, in period2 3 out of 9 cases with necrotizing pneumonia required reintervention (p=0.07). Thoracotomy was avoided in sixty eight (75%) patients (62% in period1 versus 92% in period2, p=0.001). DISCUSSION AND CONCLUSIONS: Thoracoscopic approach for empyema is feasible and safe avoiding a significant number of thoracotomies after a short learning curve. An increase of reintervention rate should be expected, but throracoscopy alone is effective in the great majority of the cases. Necrotizing pneumonia may be associated with a higher risk of reintervention, as it is a contra-indication to thoracoscopy and probably surgery. PMID- 26804665 TI - Hydrogen-fed biofilm reactors reducing selenate and sulfate: Community structure and capture of elemental selenium within the biofilm. AB - Remediation of selenate (SeO4 (2-) ) contamination through microbial reduction is often challenging due to the presence of sulfate (SO4 (2-) ), which can lead to competition for the electron donor and the co-production of toxic H2 S. Microbial reduction of SeO4 (2-) in the presence of SO4 (2-) was studied in two hydrogen based membrane biofilm reactors (MBfRs). One MBfR was initiated with SO4 (2-) reducing conditions and gradually shifted to SeO4 (2-) reduction. The second MBfR was developed with a SeO4 (2-) -reducing biofilm, followed by SO4 (2-) introduction. Biofilms within both MBfRs achieved greater than 90% SeO4 (2-) reduction, even though the SeO4 (2-) concentration ranged from 1,000-11,000 MUg/L, more than 20-200 times the maximum contaminant level for drinking water (50 MUg/L). Biofilm microbial community composition, assessed by 16S rRNA gene based amplicon pyrosequencing, was distinct between the two MBfRs and was framed by alterations in SeO4 (2-) loading. Specifically, high SeO4 (2-) loading resulted in communities mainly composed of denitrifying bacteria (e.g., Denitratisoma and Dechloromonas). In contrast, low loading led to mostly sulfate reducing bacteria (i.e., Desulfovibrio) and sulfur-oxidizing bacteria (i.e., Sulfuricurvum and Sulfurovum). SeO4 (2-) was reduced to elemental selenium (Se degrees ), which was visualized within the biofilm as crystalloid aggregates, with its fate corresponding to that of biofilm solids. In conclusion, microbial biofilm communities initiated under either SeO4 (2-) or SO4 (2-) -reducing conditions attained high SeO4 (2-) removal rates even though their microbial community composition was quite distinct. Biotechnol. Bioeng. 2016;113: 1736 1744. (c) 2016 Wiley Periodicals, Inc. PMID- 26804666 TI - Mechanism of iridium-catalysed branched-selective hydroarylation of vinyl ethers: a computational study. AB - The iridium-catalysed branched-selective hydroarylation of vinyl ethers represents a rare example of the branched-selective hydroarylation involving the non-styrene-type alkenes. Herein, we report our DFT calculations on the mechanism of this reaction. The results show that after C-H oxidative addition, instead of the widely accepted Chalk-Harrod type mechanism, the branched-selective hydroarylation may proceed through an unconventional modified Chalk-Harrod type mechanism, involving the migratory insertion into the Ir-C bond and C-H reductive elimination. Both steric and electronic effects of the alkoxy group were found to account for the complete branched selectivity. PMID- 26804667 TI - Nasal and ocular responses after specific and nonspecific nasal challenges in seasonal allergic rhinitis. AB - BACKGROUND: Different nasal challenges induce neural and immune response leading to nasal and ocular symptoms in patients with seasonal allergic rhinitis (SAR). The release of neural mediators from nasal mucosa and conjunctiva after no specific challenges in patients with SAR remains unknown. OBJECTIVES: To compare the release of mediators from the nose and conjunctiva with symptoms after different nasal challenges in patients with SAR. METHODS: Three types of consecutive nasal challenges were performed outside the pollen season in 25 patients with SAR. Challenges consisted of 500 biological units (BU) of allergen, 80 MUg of histamine, and 1 mL of 2% hypertonic saline per nostril, within 24-hour and 72-hour intervals, respectively. Before and 15 minutes after challenges, evaluation of symptoms was performed with a visual analog scale. Concentrations of tryptase, eosinophil cationic protein in nasal lavages after 15 minutes, and substance P in tears after 5 minutes were measured with enzyme immunoassays. RESULTS: Concentrations of substance P in tears were significantly higher after nonspecific challenges. Substance P concentration in tears significantly correlated with eye itchiness after histamine and hypertonic saline and with tearing after allergen. Ocular symptoms correlated significantly with tryptase concentration in nasal lavage collected 15 minutes after allergen challenge. There is a significant correlation in tear volume comparing different nasal challenges. CONCLUSIONS: Nasal challenges with allergen, histamine, or irritants outside the pollen season induce a significant increase in nasal and ocular symptoms in patients with SAR. Interaction of the early-phase response and neurogenic inflammation define the pattern and severity of eye symptoms. PMID- 26804668 TI - Electrosonodiagnosis in Carpal Tunnel Syndrome: A Proposed Diagnostic Algorithm Based on an Analytic Literature Review. AB - BACKGROUND: Suspected carpal tunnel syndrome (CTS) remains the most common clinical scenario prompting referral for electrodiagnostic (EDx) studies to identify objective correlates of reported subjective symptoms and clinical examination findings. Despite much debate and a rapidly expanding literature, identification of an optimal algorithm for diagnosing focal median mononeuropathy at the wrist (FMMW) associated with CTS signs and symptoms remains elusive. The introduction and rapid dissemination of peripheral nerve ultrasound imaging (PN USI) of the median nerve has raised new questions regarding the relative value of structural information from PN-USI versus physiological information from EDx in the diagnosis of FMMW, as well as the significance of various clinical signs and symptoms suggestive of CTS. The means by which PN-USI and EDx may be optimally deployed and integrated in the process of diagnosing FMMW remains to be clearly delineated. OBJECTIVE: To complete an analytical literature review to guide the formulation of a clinical diagnostic algorithm (CDA) integrating the use of PN USI and EDx for the optimal detection of FMMW in the context of making a clinical diagnosis of CTS. DATA SOURCES: A structured literature review was performed on the MEDLINE medical literature database accessed through PubMed. ANALYSIS: Papers with particular relevance and connection to the goal of formulating the CDA were selected from the identified studies. Studies specifically examining the correlations between systematically documented clinical symptomatology, EDx findings, and PN-USI findings were reviewed for consistent outcomes that could be incorporated into a CDA to guide the integration of these two complementary technologies in the diagnostic process. LIMITATIONS: The formulation of the algorithm was limited to measures with established validity that can be readily obtained by means of widely accepted protocols using standard EDx and ultrasound equipment. The formulated algorithm assumes a consistent association between pathophysiology and anatomical deformation of the median nerve, which may not occur in certain situations. It may also not be as accurately applied to patients with CTS with significant comorbid neuromuscular conditions. CONCLUSIONS: An algorithm has been developed and presented, and illustrated as a flow chart, based on findings reported in the relevant reviewed literature in which PN-USI is proposed as a painless and rapidly performed screening test for FMMW to be completed before subjecting a patient to a systematic EDx testing process. PMID- 26804669 TI - An improved parameter estimation scheme for image modification detection based on DCT coefficient analysis. AB - Most of the existing image modification detection methods which are based on DCT coefficient analysis model the distribution of DCT coefficients as a mixture of a modified and an unchanged component. To separate the two components, two parameters, which are the primary quantization step, Q1, and the portion of the modified region, alpha, have to be estimated, and more accurate estimations of alpha and Q1 lead to better detection and localization results. Existing methods estimate alpha and Q1 in a completely blind manner, without considering the characteristics of the mixture model and the constraints to which alpha should conform. In this paper, we propose a more effective scheme for estimating alpha and Q1, based on the observations that, the curves on the surface of the likelihood function corresponding to the mixture model is largely smooth, and alpha can take values only in a discrete set. We conduct extensive experiments to evaluate the proposed method, and the experimental results confirm the efficacy of our method. PMID- 26804670 TI - 5-Alpha reductase inhibitor use and prostate cancer survival in the Finnish Prostate Cancer Screening Trial. AB - Randomized clinical trials have shown that use of 5alpha-reductase inhibitors (5 ARIs) lowers overall prostate cancer (PCa) risk compared to placebo, while the proportion of Gleason 8-10 tumors is elevated. It is unknown whether this affects PCa-specific survival. We studied disease-specific survival by 5-ARI usage in a cohort of 6,537 prostate cancer cases diagnosed in the Finnish Prostate Cancer Screening Trial and linked to the national prescription database for information on medication use. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals for prostate cancer-specific deaths. For comparison, survival among alpha-blocker users was also evaluated. During the median follow-up of 7.5 years after diagnosis a total of 2,478 men died; 617 due to prostate cancer and 1,861 due to other causes. The risk of prostate cancer death did not differ between 5-ARI users and nonusers (multivariable adjusted HR 0.94, 95% CI 0.72-1.24 and HR 0.98, 95% CI 0.69-1.41 for usage before and after the diagnosis, respectively). Alpha-blocker usage both before and after diagnosis was associated with increased risk of prostate cancer death (HR 1.29, 95% CI 1.08 1.54 and HR 1.56, 95% CI 1.30-1.86, respectively). The risk increase vanished in long-term alpha-blocker usage. Use of 5-ARIs does not appear to affect prostate cancer mortality when used in management of benign prostatic hyperplasia. Increased risk associated with alpha-blocker usage should prompt further exploration on the prognostic role of lower urinary tract symptoms. PMID- 26804704 TI - Induction of cell death by the novel proteasome inhibitor marizomib in glioblastoma in vitro and in vivo. AB - New therapies for glioblastoma (GBM) are needed, as five-year survival is <10%. The proteasome inhibitor marizomib (MRZ) has inhibitory and death-inducing properties unique from previous inhibitors such as bortezomib (BTZ), and has not been well examined in GBM. We evaluated the mechanism of death and in vivo properties of MRZ in GBM. The activation kinetics of initiator caspases 2, 8, and 9 were assessed using chemical and knockdown strategies to determine their contribution to cell death. Blood brain barrier permeance and proteasome inhibition by MRZ and BTZ were examined in an orthotopic GBM model. Blockade of caspase 9, relative to other caspases, was most protective against both MRZ and BTZ. Only MRZ increased the proteasome substrate p27 in orthotopic brain tumors after a single injection, while both MRZ and BTZ increased p21 levels after multiple treatments. Cleavage of caspase substrate lamin A was increased in orthotopic brain tumors from mice treated with MRZ or BTZ and the histone deacetylase inhibitor vorinostat. Our data indicate that MRZ induces caspase 9 dependent death in GBM, suggesting drug efficacy biomarkers and possible resistance mechanisms. MRZ reaches orthotopic brain tumors where it inhibits proteasome function and increases death in combination with vorinostat. PMID- 26804705 TI - Aliskiren improves endothelium-dependent relaxation of thoracic aorta by activating PI3K/Akt/eNOS signal pathway in SHR. AB - Aliskiren, a direct renin blocker, has been approved for the treatment of hypertension. However, the potential role of aliskiren on vascular endothelial function in spontaneously hypertensive rats (SHR) remains unclear. In the present study, male SHRs at 12 weeks of age were orally administrated 30 mg/kg per day or 60 mg/kg per day aliskiren. After a 4-week treatment, aliskiren showed a significant effect on the reduction of blood pressure at a dosage of 60 mg/kg per day, but not of 30 mg/kg per day. Moreover, both dosages of aliskiren improved endothelium-dependent relaxation, reduced dihydroethidium fluorescence intensity, decreased level of malondialdehyde but heightened total antioxidant capacity and superoxide dismutase activity in thoracic aorta in SHR. Aliskiren also markedly increased expression of p85alpha, an important subunit of phosphatidylinositol 3 kinase (PI3K), enhancing phosphorylation of protein kinase B (Akt) at Ser473 and endothelial nitric oxide synthase (eNOS) at Ser1177, as well as cyclic guanosine 3'5'-monophosphate (cGMP, a sensitive index of biological activity of nitric oxide) concentration. Furthermore, both anti-oxidative and endothelium protective effects of aliskiren were diminished when PI3K was inhibited in vivo. The data presented here indicates that, aliskiren improves endothelium-dependent relaxation of thoracic aorta in SHR, predominantly through attenuating oxidative stress and activation of the PI3K/Akt/eNOS pathway. These data might propose novel strategies to prevent and improve vascular endothelial dysfunction. PMID- 26804707 TI - The classic EDCs, phthalate esters and organochlorines, in relation to abnormal sperm quality: a systematic review with meta-analysis. AB - The association between endocrine disrupting chemicals (EDCs) and human sperm quality is controversial due to the inconsistent literature findings, therefore, a systematic review with meta-analysis was performed. Through the literature search and selection based on inclusion criteria, a total of 9 studies (7 cross sectional, 1 case-control, and 1 pilot study) were analyzed for classic EDCs (5 studies for phthalate esters and 4 studies for organochlorines). Funnel plots revealed a symmetrical distribution with no evidence of publication bias (Begg's test: intercept = 0.40; p = 0.692). The summary odds ratios (OR) of human sperm quality associated with the classic EDCs was 1.67 (95% CI: 1.31-2.02). After stratification by specific chemical class, consistent increases in the risk of abnormal sperm quality were found in phthalate ester group (OR = 1.52; 95% CI: 1.09-1.95) and organochlorine group (OR = 1.98; 95% CI: 1.34-2.62). Additionally, identification of official data, and a comprehensive review of the mechanisms were performed, and better elucidated the increased risk of these classic EDCs on abnormal sperm quality. The present systematic review and meta-analysis helps to identify the impact of classic EDCs on human sperm quality. However, it still highlights the need for additional epidemiological studies in a larger variety of geographic locations. PMID- 26804709 TI - Fluorescent aliphatic hyperbranched polyether: chromophore-free and without any N and P atoms. AB - The strong fluorescence, in both the solution and the bulk state, of a chromophore-free aliphatic hyperbranched polyether which does not contain N and P atoms was reported for the first time. Effects of concentration and solvent solubility were measured. Its ethanol solution shows a strong blue-green fluorescence (Yu = 0.11-0.39), and its fluorescence shows a strong selective quenching with respect to Fe(3+). PMID- 26804710 TI - Safe and efficient method for cryopreservation of human induced pluripotent stem cell-derived neural stem and progenitor cells by a programmed freezer with a magnetic field. AB - Stem cells represent a potential cellular resource in the development of regenerative medicine approaches to the treatment of pathologies in which specific cells are degenerated or damaged by genetic abnormality, disease, or injury. Securing sufficient supplies of cells suited to the demands of cell transplantation, however, remains challenging, and the establishment of safe and efficient cell banking procedures is an important goal. Cryopreservation allows the storage of stem cells for prolonged time periods while maintaining them in adequate condition for use in clinical settings. Conventional cryopreservation systems include slow-freezing and vitrification both have advantages and disadvantages in terms of cell viability and/or scalability. In the present study, we developed an advanced slow-freezing technique using a programmed freezer with a magnetic field called Cells Alive System (CAS) and examined its effectiveness on human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs). This system significantly increased cell viability after thawing and had less impact on cellular proliferation and differentiation. We further found that frozen-thawed hiPSC-NS/PCs were comparable with non-frozen ones at the transcriptome level. Given these findings, we suggest that the CAS is useful for hiPSC-NS/PCs banking for clinical uses involving neural disorders and may open new avenues for future regenerative medicine. PMID- 26804708 TI - A chronic care ostomy self-management program for cancer survivors. AB - BACKGROUND: Individuals with ostomies experience extensive changes in health related quality of life (HRQOL) and daily routine. Patients and families are typically forced to use trial and error to improve self-management. METHODS: This is a longitudinal one-group design pilot study of a five-session ostomy self-care curriculum based on the Chronic Care Model to improve HRQOL and self-management for cancer survivors with ostomies. Participants were surveyed to evaluate each session. Multiple instruments were administered to examine outcomes at baseline, post-intervention, and at 6-month follow-up (Patient Activation Measure, self efficacy, Hospital Anxiety and Depression Scale, Ways of Coping, Group Health Association of America Satisfaction with ostomy care survey, and the City of Hope Quality of Life Ostomy). Changes from pre-intervention to post-intervention and pre-intervention to follow-up were evaluated with paired t-tests. Text responses were coded and evaluated for important themes and recommendations. RESULTS: Thirty-eight subjects participated in the study. Most had a history of rectal cancer (60.5%) or bladder cancer (28.9%). Participants rated the overall program high (4.4-4.8 on 5-point scale). Text feedback indicated that participants enjoyed the group forums, wanted more participants, and more hands-on training. Scores on multiple surveys were shown to be improved and sustained, including patient activation (p = 0.0004), self-efficacy (p = 0.006), total HRQOL (p = 0.01), physical well-being (p = 0.005), and social well-being (p = 0.002). Survivor anxiety was significantly reduced by follow-up (p = 0.047). CONCLUSIONS: This self-management ostomy program can help cancer survivors with ostomies adapt to their stoma. Initiating this program in the community setting would be beneficial to many cancer survivors. PMID- 26804712 TI - Benzodiazepine use associated with co-morbid post-traumatic stress syndrome and depression in older adults seeking services in general medical settings. AB - BACKGROUND: Benzodiazepines (BZD) should be limited in older adults. This study aimed to determine the association between BZD use and the presence of a probable post-traumatic stress syndrome (PTSS) and whether this association is dependent on gender and co-morbid physical and mental conditions. METHODS: Data were retained from the Etude sur la Sante des Aines (ESA) - Services study (2011-2013) and included 1,453 older adults (>=65 years) who completed a face to face at-home interview, who were covered under Quebec's public drug insurance plan, and had given permission to access their Regie de l'Assurance Maladie du Quebec (RAMQ) medical and pharmaceutical services data. The presence of a PTSS was measured using the Impact of Event Scale-Revised (IES-R). The use of BZD and antidepressants in the year prior to interview was ascertained from data reported in the RAMQ drug registry. The presence of depression and an anxiety disorder was assessed with the ESA-Questionnaire which was based on DSM-5 criteria. The interaction between PTSS and gender, depression, anxiety, and multi-morbidity was also assessed. RESULTS: The prevalence of PTSS and BZD use reached 4.5% and 31.2%. Participants with PTSS were 1.9 (95% CI = 1.1-3.2) times more likely to use BZD. The presence of depression had a negative impact on the association between BZD use and PTSS (p = 0.04). CONCLUSION: The use of BZD in older adults with PTSS is still prevalent today. Differences in benzodiazepine prescribing practices for more complex co-morbid psychiatric cases needs to be further studied. PMID- 26804713 TI - [Anesthetic considerations for a patient with hereditary angioedema - A clinical case]. AB - Hereditary angioedema (HAE), with an estimated prevalence of 1:50 000, is a rare but potentially fatal disease. It may present with recurrent systemic edema of the subcutaneous tissue and mucous membranes. Patients with HAE are at increased risk for clinical worsening with surgical stress, and may develop respiratory distress syndrome due to impaired airway and hemodynamic instability. The perioperative management of these patients requires specific interventions. We present a clinical case of a woman, 50 years old, with HAE type II scheduled for ureteral stent placement via endoscopic approach. PMID- 26804714 TI - [Postoperative visual loss due to conversion disorder after spine surgery: a case report]. AB - BACKGROUND AND OBJECTIVE: Patients undergoing spinal surgeries may develop postoperative visual loss. We present a case of total bilateral visual loss in a patient who, despite having clinical and surgical risk factors for organic lesion, evolved with visual disturbance due to conversion disorder. CASE REPORT: A male patient, 39 years old, 71kg, 1.72 m, ASA I, admitted to undergo fusion and discectomy at L4-L5 and L5-S1. Venoclysis, cardioscopy, oximetry, NIBP; induction with remifentanil, propofol and rocuronium; intubation with ETT (8.0mm) followed by capnography and urinary catheterization for diuresis. Maintenance with full target-controlled intravenous anesthesia. During fixation and laminectomy, the patient developed severe bleeding and hypovolemic shock. After 30minutes, hemostasis and hemodynamic stability was achieved with infusion of norepinephrine, volume expansion, and blood products. In the ICU, the patient developed mental confusion, weakness in the limbs, and bilateral visual loss. It was not possible to identify clinical, laboratory or image findings of organic lesion. He evolved with episodes of anxiety, emotional lability, and language impairment; the hypothesis of conversion syndrome with visual component was raised after psychiatric evaluation. The patient had complete resolution of symptoms after visual education and introduction of low doses of antipsychotic, antidepressant, and benzodiazepine. Other symptoms also regressed, and the patient was discharged 12 days after surgery. After 60 days, the patient had no more symptoms. CONCLUSIONS: Conversion disorders may have different signs and symptoms of non-organic origin, including visual component. It is noteworthy that the occurrence of this type of visual dysfunction in the postoperative period of spinal surgery is a rare event and should be remembered as a differential diagnosis. PMID- 26804715 TI - Effects of Device-Facilitated Isometric Progressive Resistance Oropharyngeal Therapy on Swallowing and Health-Related Outcomes in Older Adults with Dysphagia. AB - Swallowing disorders (dysphagia) are associated with malnutrition, aspiration pneumonia, and mortality in older adults. Strengthening interventions have shown promising results, but the effectiveness of treating dysphagia in older adults remains to be established. The Swallow STRengthening OropharyNGeal (Swallow STRONG) Program is a multidisciplinary program that employs a specific approach to oropharyngeal strengthening-device-facilitated (D-F) isometric progressive resistance oropharyngeal (I-PRO) therapy-with the goal of reducing health-related sequelae in veterans with dysphagia. Participants completed 8 weeks of D-F I-PRO therapy while receiving nutritional counseling and respiratory status monitoring. Assessments were completed at baseline, 4, and 8 weeks. At each visit, videofluoroscopic swallowing studies were performed. Dietary and swallowing related quality of life questionnaires were administered. Long-term monitoring for 6-17 months after enrollment allowed for comparison of pneumonia incidence and hospitalizations to the 6-17 months before the program. Veterans with dysphagia confirmed with videofluoroscopy (N = 56; 55 male, 1 female; mean age 70) were enrolled. Lingual pressures increased at anterior (effect estimate = 92.5, P < .001) and posterior locations (effect estimate = 85.4, P < .001) over 8 weeks. Statistically significant improvements occurred on eight of 11 subscales of the Quality of Life in Swallowing Disorders (SWAL-QOL) Questionnaire (effect estimates = 6.5-19.5, P < .04) and in self-reported sense of effort (effect estimate = -18.1, P = .001). Higher Functional Oral Intake Scale scores (effect estimate = 0.4, P = .02) indicated that participants were able to eat less restrictive diets. There was a 67% reduction in pneumonia diagnoses, although the difference was not statistically significant. The number of hospital admissions decreased significantly (effect estimate = 0.96; P = .009) from before to after enrollment. Findings suggest that the Swallow STRONG multidisciplinary oropharyngeal strengthening program may be an effective treatment for older adults with dysphagia. PMID- 26804716 TI - Use of the new da Vinci Xi(r) during robotic rectal resection for cancer: a pilot matched-case comparison with the da Vinci Si(r). AB - BACKGROUND: The aim of this study was to compare the short-term outcomes of robotic rectal resection with total mesorectal excision (TME) for rectal cancer, with the use of the new da Vinci Xi(r) (Xi-RobTME group) and the da Vinci Si(r) (Si-RobTME group). METHODS: Ten patients with histologically confirmed rectal cancer underwent robot-assisted TME with the use of the new da Vinci Xi. The outcomes of Xi-RobTME group were compared with a Si-RobTME group selected using a case-matched methodology. RESULTS: Overall operative times and mean hospital stays were shorter in the Xi-RobTME group. Surgeries were fully robotic with a complete take-down of the splenic flexure in all Xi-RobTME cases, while only four cases of the Si-RobTME group were fully robotic, with two cases of complete take down of the splenic flexure. CONCLUSIONS: The new da Vinci Xi could offer some advantages with respect to the da Vinci Si in rectal resection for cancer. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26804718 TI - Older people's involvement in activities related to meals in nursing homes. AB - AIMS AND OBJECTIVES: To explore how residents in nursing homes perceive their participation in activities related to food and meals, and possible factors influencing their involvement. BACKGROUND: Eating and drinking are fundamental human needs and consequently essential parts of nursing and nursing care. Therefore and as part of nursing care, encouraging older people in nursing homes to engage in different mealtime activities could be one way to increase participation in activities of daily living and more optimal nutrition status among older people. DESIGN: A cross-sectional survey design was used. METHODS: A total of 204 residents (88%) in one Norwegian county agreed to participate and completed a face-to-face interview questionnaire about food and meal experiences. Descriptive and comparative statistics was used. RESULTS: Close to 30% of the residents were vulnerable to malnourishment. None of the residents were involved in menu planning, and more than 90% did not participate in food preparation or setting/clearing tables. Ten per cent were able to choose where they could eat and 5% when they could eat. Older persons living in nursing homes with more than 80 residents and those younger than 65 years of age participated the most, while older people with poor appetites were able to choose more often where they wanted to eat, compared to those with a healthy appetite. CONCLUSION: The residents in this study appeared to be vulnerable to malnourishment. The results indicated that they only to a limited extent were involved in activities concerning food and meals at the nursing homes. IMPLICATIONS FOR PRACTICE: Management and nurses should focus on residents' eating and drinking, which are essentials of nursing care. The residents should be asked whether they would like to participate in different mealtime activities. Further, a person-centred care approach that facilitates activities concerning food and meals should be promoted. PMID- 26804717 TI - Persistent order due to transiently enhanced nesting in an electronically excited charge density wave. AB - Non-equilibrium conditions may lead to novel properties of materials with broken symmetry ground states not accessible in equilibrium as vividly demonstrated by non-linearly driven mid-infrared active phonon excitation. Potential energy surfaces of electronically excited states also allow to direct nuclear motion, but relaxation of the excess energy typically excites fluctuations leading to a reduced or even vanishing order parameter as characterized by an electronic energy gap. Here, using femtosecond time- and angle-resolved photoemission spectroscopy, we demonstrate a tendency towards transient stabilization of a charge density wave after near-infrared excitation, counteracting the suppression of order in the non-equilibrium state. Analysis of the dynamic electronic structure reveals a remaining energy gap in a highly excited transient state. Our observation can be explained by a competition between fluctuations in the electronically excited state, which tend to reduce order, and transiently enhanced Fermi surface nesting stabilizing the order. PMID- 26804719 TI - Why is polypharmacy increasing in aged care facilities? The views of Australian health care professionals. AB - RATIONALE, AIMS AND OBJECTIVES: The prevalence of polypharmacy in residential aged care facilities (RACFs) is high and increasing. Although not necessarily inappropriate, polypharmacy has been associated with drug interactions, adverse drug events, geriatric syndromes and hospital admissions. The aim of this study was to identify and prioritize factors contributing to the increasing prevalence of polypharmacy in RACFs. METHODS: Seventeen health care professionals from metropolitan and regional Victoria and South Australia identified and prioritized factors using a modified nominal group technique. RESULTS: The top five factors ranked from most important to fifth most important were 'changes in resident mix', 'increasing numbers of prescribers and the reluctance of one prescriber to discontinue a medicine commenced by another prescriber', 'better adherence to clinical practice guidelines', 'increasing reliance on locums' and 'greater recognition and pharmacological management of pain'. CONCLUSIONS: Reasons for the increase in polypharmacy are multifactorial. Understanding the factors contributing to polypharmacy may help to guide future research and develop interventions to manage polypharmacy in RACFs. PMID- 26804720 TI - DBP-induced endoplasmic reticulum stress in male germ cells causes autophagy, which has a cytoprotective role against apoptosis in vitro and in vivo. AB - Recently, spermatogenic cell apoptosis was shown to play a key role in the induction of testicular atrophy by dibutyl phthalate (DBP), thus causing reproductive toxicology. However, the molecular events induced by DBP in apoptotic germ cells remain unclear. In the present study, the mouse spermatocyte derived GC-2 cell line was exposed to different doses of DBP. We found that DBP induced marked apoptosis in GC-2 cells. The levels of the major endoplasmic reticulum (ER) stress markers GRP-78, ATF-6, and p-EIF2alpha were elevated when GC-2 cells were exposed to 25 MUM DBP and increased in a dose-dependent manner at higher concentrations. Furthermore, at a concentration that resulted in significant apoptosis (100 MUM), CHOP, which plays a convergent role in ER stress mediated apoptosis and is regulated by various upstream ER stress signals, was activated and partially contributed to the DBP-induced apoptosis. However, inhibition of ER stress by 4-PBA, a chemical with chaperone-like activities, augmented the GC-2 cell apoptosis induced by DBP. Further experiments demonstrated that DBP-induced ER stress additionally had a protective role, mediated through the activation of autophagy. These results were confirmed in prepubertal rat testis germ cells; DBP treatment significantly induced testicular atrophy, accompanied by apoptosis, ER stress, and autophagy. Inhibition of ER stress and autophagy significantly aggravated the DBP-induced damage to the germ cells and testes. Taken together, our data suggest that DBP-induced ER stress in germ cells has a cytoprotective effect that is mediated through autophagy activation. These findings provide novel clues regarding the molecular events involved in DBP-induced germ cell apoptosis. PMID- 26804722 TI - Resolution of HELLP syndrome after selective feticide for trisomy 21 in discordant twins - A case report. PMID- 26804723 TI - Temperature effect on triacylglycerol species in seed oil from high stearic sunflower lines with different genetic backgrounds. AB - BACKGROUND: This study characterized the influence of temperature during grain filling on the saturated fatty acid distribution in triacylglycerol molecules from high stearic sunflower lines with different genetic backgrounds. Two growth chamber experiments were conducted with day/night temperatures of 16/16, 26/16, 26/26 and 32/26 degrees C. RESULTS: In all genotypes, independently of the genetic background, higher temperatures increased palmitic and oleic acid and reduced linoleic acid concentrations. Increasing night temperature produced an increase in saturated-unsaturated-saturated species, indicating a more symmetrical distribution of saturated fatty acids. The solid fat index was more affected by temperature during grain filling in lines with high linoleic than high oleic background. Higher variations in symmetry among night temperatures were observed in lines with high oleic background, which are more stable in fatty acid composition. CONCLUSION: The effect of temperature on triacylglycerol composition is not completely explained by its effect on fatty acid composition. Thus night temperature affects oil properties via its effects on fatty acid synthesis and on the distribution of fatty acids in the triacylglycerol molecules. (c) 2016 Society of Chemical Industry. PMID- 26804725 TI - Polymeric capsule-cushioned leukocyte cell membrane vesicles as a biomimetic delivery platform. AB - We report a biomimetic delivery of microsized capsule-cushioned leukocyte membrane vesicles (CLMVs) through the conversion of freshly reassembled leukocyte membrane vesicles (LMVs), including membrane lipids and membrane-bound proteins onto the surface of layer-by-layer assembled polymeric multilayer microcapsules. The leukocyte membrane coating was verified by using electron microscopy, a quartz crystal microbalance, dynamic light scattering, and confocal laser scanning microscopy. The resulting CLMVs have the ability to effectively evade clearance by the immune system and thus prolong the circulation time in mice. Moreover, we also show that the right-side-out leukocyte membrane coating can distinctly improve the accumulation of capsules in tumor sites through the molecular recognition of membrane-bound proteins of CLMVs with those of tumor cells in vitro and in vivo. The natural cell membrane camouflaged polymeric multilayer capsules with the immunosuppressive and tumor-recognition functionalities of natural leukocytes provide a new biomimetic delivery platform for disease therapy. PMID- 26804726 TI - Nanoplasmonic Photoluminescence Spectroscopy at Single-Particle Level: Sensing for Ethanol Oxidation. AB - Surface plasmon resonances of metal nanoparticles have shown significant promise for the use of solar energy to drive catalytic chemical reactions. More importantly, understanding and monitoring such catalytic reactions at single nanoparticle level is crucial for the study of local reaction processes. Herein, using plasmonic photoluminescence (PL) spectroscopy, we describe a novel sensing method for catalytic ethanol oxidation reactions at the single-nanoparticle level. The Au nanorod monitors the interfacial interaction with ethanol during the catalytic reaction through the PL intensity changes in the single-particle PL spectra. The analysis of energy relaxation of excited electron-hole pairs indicates the relationship between the PL quenching and ethanol oxidation reaction on the single Au nanorod. PMID- 26804727 TI - The Enantioselective Dakin-West Reaction. AB - Here we report the development of the first enantioselective Dakin-West reaction, yielding alpha-acetamido methylketones with up to 58 % ee with good yields. Two of the obtained products were recrystallized once to achieve up to 84 % ee. The employed methylimidazole-containing oligopeptides catalyze both the acetylation of the azlactone intermediate and the terminal enantioselective decarboxylative protonation. We propose a dispersion-controlled reaction path that determines the asymmetric reprotonation of the intermediate enolate after the decarboxylation. PMID- 26804729 TI - Follicular fluorescence quantity to characterize acne severity: a validation study. AB - BACKGROUND: Porphyrins are native fluorophores in the follicle openings, visible under ultraviolet-A light. Acne severity might be associated with increased Propionibacterium acnes colonization and porphyrin production. Aim of this study was to investigate whether the parameter fluorescence quantity can be used to measure acne severity. METHODS: A validation study was conducted in 24 patients with acne using split-face design. Acne severity was measured using Investigator Static Global Assessment scores and lesion counts. Reliability, construct validity and sensitivity to change in fluorescence quantity were investigated. RESULTS: Mean baseline Investigator Static Global Assessment score was 2.7 (SD 0.1). Mean baseline fluorescence quantities were 24.8 (SD 4.0) on the cheek and 20.3 (SD 4.6) on the chin. On day 25, values ranged from 6.0 (SD 6.0) to 18.1 (SD 18.4) on the cheek and from 2.6 (SD 4.4) to 14.7 (SD 16.2) on the chin. The intraclass correlation coefficients of fluorescence quantity ranged from 0.513 to 0.987. Effect sizes for fluorescence measurements were highest on the chin and cheek ranging from 0.24 to 0.77 and 0.32 to 0.75, respectively. CONCLUSION: Fluorescence quantity indicates acne severity, especially on the inner cheek and chin areas. Fluorescence quantity is reliable but is not as sensitive as manual lesion counting. PMID- 26804731 TI - Adult Sexual Outcomes of Child Sexual Abuse Vary According to Relationship Status. AB - This study tested a moderation model in which the association between child sexual abuse severity and negative sexual outcomes (i.e., sexual avoidance and compulsivity) differed as a function of relationships status (i.e., single, cohabiting, and married individuals). A sample of 1,033 adults completed self report questionnaires online, and 21.5% reported childhood sexual abuse. Path analyses indicated that child sexual abuse severity was associated with higher sexual compulsivity in single individuals, both higher sexual avoidance and compulsivity in cohabiting individuals, and higher sexual avoidance in married individuals. The moderation model was invariant across men and women. These results suggest that the time course of negative sexual outcomes associated with child sexual abuse may follow distinct patterns of expression according to relationship status. PMID- 26804733 TI - How Does Streptococcus pneumoniae Invade the Brain? AB - Streptococcus pneumoniae (the pneumococcus) is the major cause of bacterial meningitis. The mechanisms by which pneumococci from the bloodstream penetrate the blood-brain barrier to reach the brain are not fully understood. Receptor mediated adhesion of the bacteria to the brain endothelium is considered a key event leading to meningitis development. The aim of this review is to discuss recent advances and perspectives related to the interactions of S. pneumoniae with the blood-brain barrier during the events leading to meningitis. Altogether, the available data suggest that, by precisely defining the pathways and ligands by which S. pneumoniae adheres to specific receptors, it may be possible to interfere with the respective mechanisms and develop strategies to prevent or even cure pneumococcal meningitis. PMID- 26804735 TI - Reducing treatment-related mortality in childhood cancers. PMID- 26804737 TI - Plasma proteome coverage is increased by unique peptide recovery from sodium deoxycholate precipitate. AB - The ionic detergent sodium deoxycholate (SDC) is compatible with in-solution tryptic digestion and LC-MS/MS-based shotgun proteomics by virtue of being easy to separate from the peptide products via precipitation in acidic buffers. However, it remains unclear whether unique human peptides co-precipitate with SDC during acid treatment of complex biological samples. In this study, we demonstrate for the first time that a large quantity of unique peptides in human blood plasma can be co-precipitated with SDC using an optimized sample preparation method prior to shotgun proteomic analysis. We show that the plasma peptides co-precipitated with SDC can be successfully recovered using a sequential re-solubilization and precipitation procedure, and that this approach is particularly efficient at the extraction of long peptides. Recovery of peptides from the SDC pellet dramatically increased overall proteome coverage (>60 %), thereby improving the identification of low-abundance proteins and enhancing the identification of protein components of membrane-bound organelles. In addition, when we analyzed the physiochemical properties of the co precipitated peptides, we observed that SDC-based sample preparation improved the identification of mildly hydrophilic/hydrophobic proteins that would otherwise be lost upon discarding the pellet. These data demonstrate that the optimized SDC protocol is superior to sodium dodecyl sulfate (SDS)/urea treatment for identifying plasma biomarkers by shotgun proteomics. PMID- 26804736 TI - Screening, Synthesis, and In Vitro Evaluation of Vinyl Sulfones as Inhibitors of Complement-Dependent Cytotoxicity in Neuromyelitis Optica. AB - Neuromyelitis optica (NMO) is a demyelinating autoimmune disease of the optic nerve and spinal cord triggered by binding of NMO-specific immunoglobulin G (NMO IgG) auto-antibodies to the water channel aquaporin-4 (AQP4) in astrocytes. To find potential NMO therapeutics, a screening system was established and used to identify inhibitors of NMO-IgG-mediated complement-dependent cytotoxicity (CDC). The screening of approximately 400 compounds yielded potent hit compounds with inhibitory effects against CDC in U87-MG cells expressing human AQP4. Derivatives of the hit compounds were synthesized and evaluated for their inhibition of CDC. Of the small molecules synthesized, (E)-1-(2-((4-methoxyphenyl)sulfonyl)vinyl)-[4 [(3-trifluoromethyl)phenyl] methoxy]benzene (5 c) showed the most potent activity in both stably transfected U87-MG cells and mice-derived astrocytes. The results of this study suggest that 5 c, which targets NMO-IgG-specific CDC, may be useful as a research tool and a potential candidate for therapeutic development for the treatment of NMO. PMID- 26804738 TI - Using design of experiments to optimize derivatization with methyl chloroformate for quantitative analysis of the aqueous phase from hydrothermal liquefaction of biomass. AB - Hydrothermal liquefaction is a promising technique for the production of bio-oil. The process produces an oil phase, a gas phase, a solid residue, and an aqueous phase. Gas chromatography coupled with mass spectrometry is used to analyze the complex aqueous phase. Especially small organic acids and nitrogen-containing compounds are of interest. The efficient derivatization reagent methyl chloroformate was used to make analysis of the complex aqueous phase from hydrothermal liquefaction of dried distillers grains with solubles possible. A circumscribed central composite design was used to optimize the responses of both derivatized and nonderivatized analytes, which included small organic acids, pyrazines, phenol, and cyclic ketones. Response surface methodology was used to visualize significant factors and identify optimized derivatization conditions (volumes of methyl chloroformate, NaOH solution, methanol, and pyridine). Twenty nine analytes of small organic acids, pyrazines, phenol, and cyclic ketones were quantified. An additional three analytes were pseudoquantified with use of standards with similar mass spectra. Calibration curves with high correlation coefficients were obtained, in most cases R (2) > 0.991. Method validation was evaluated with repeatability, and spike recoveries of all 29 analytes were obtained. The 32 analytes were quantified in samples from the commissioning of a continuous flow reactor and in samples from recirculation experiments involving the aqueous phase. The results indicated when the steady-state condition of the flow reactor was obtained and the effects of recirculation. The validated method will be especially useful for investigations of the effect of small organic acids on the hydrothermal liquefaction process. PMID- 26804741 TI - Novel Strategies for the Treatment of Pseudomonas aeruginosa Infections. AB - Infections with Pseudomonas aeruginosa have become a concerning threat in hospital-acquired infections and for cystic fibrosis patients. The major problem leading to high mortality lies in the appearance of drug-resistant strains. Therefore, a vast number of approaches to develop novel anti-infectives is currently pursued. These diverse strategies span from killing (new antibiotics) to disarming (antivirulence) the pathogen. Particular emphasis lies on the development of compounds that inhibit biofilms formed in chronic infections to restore susceptibility toward antibiotics. Numerous promising results are summarized in this perspective. Antibiotics with a novel mode of action will be needed to avoid cross resistance against currently used therapeutic agents. Importantly, antivirulence drugs are expected to yield a significantly reduced rate of resistance development. Most developments are still far from the application. It can however be expected that combination therapies, also containing antivirulence agents, will pave the way toward novel treatment options against P. aeruginosa. PMID- 26804739 TI - Nimbolide inhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal transition. AB - The mortality and morbidity rates of pancreatic cancer are high because of its extremely invasive and metastatic nature. Its lack of symptoms, late diagnosis and chemo-resistance and the ineffective treatment modalities warrant the development of new chemo-therapeutic agents for pancreatic cancer. Agents from medicinal plants have demonstrated therapeutic benefits in various human cancers. Nimbolide, an active molecule isolated from Azadirachta indica, has been reported to exhibit several medicinal properties. This study assessed the anticancer properties of nimbolide against pancreatic cancer. Our data reveal that nimbolide induces excessive generation of reactive oxygen species (ROS), thereby regulating both apoptosis and autophagy in pancreatic cancer cells. Experiments with the autophagy inhibitors 3-methyladenine and chloroquine diphosphate salt and the apoptosis inhibitor z-VAD-fmk demonstrated that nimbolide-mediated ROS generation inhibited proliferation (through reduced PI3K/AKT/mTOR and ERK signaling) and metastasis (through decreased EMT, invasion, migration and colony forming abilities) via mitochondrial-mediated apoptotic cell death but not via autophagy. In vivo experiments also demonstrated that nimbolide was effective in inhibiting pancreatic cancer growth and metastasis. Overall, our data suggest that nimbolide can serve as a potential chemo-therapeutic agent for pancreatic cancer. PMID- 26804742 TI - Tailoring Staircase-like Hysteresis Loops in Electrodeposited Trisegmented Magnetic Nanowires: a Strategy toward Minimization of Interwire Interactions. AB - A new strategy to minimize magnetic interactions between nanowires (NWs) dispersed in a fluid is proposed. Such a strategy consists of preparing trisegmented NWs containing two antiparallel ferromagnetic segments with dissimilar coercivity separated by a nonmagnetic spacer. The trisegmented NWs exhibit a staircase-like hysteresis loop with tunable shape that depends on the relative length of the soft- and hard-magnetic segments and the respective values of saturation magnetization. Such NWs are prepared by electrodepositing CoPt/Cu/Ni in a polycarbonate (PC) membrane. The antiparallel alignment is set by applying suitable magnetic fields while the NWs are still embedded in the PC membrane. Analytic calculations are used to demonstrate that the interaction magnetic energy from fully compensated trisegmented NWs with antiparallel alignment is reduced compared to a single-component NW with the same length or the trisegmented NWs with the two ferromagnetic counterparts parallel to each other. The proposed approach is appealing for the use of magnetic NWs in certain biological or catalytic applications where the aggregation of NWs is detrimental for optimized performance. PMID- 26804743 TI - Versatile synthesis of cationic N-heterocyclic carbene-gold(i) complexes containing a second ancillary ligand. Design of heterobimetallic ruthenium-gold anticancer agents. AB - We describe a versatile and quick route to cationic gold(i) complexes containing N-heterocyclic carbenes and a second ancillary ligand (such as phosphanes, phosphites, arsines and amines) of interest for the synthesis of compounds with potential catalytic and medicinal applications. The general synthetic strategy has been applied in the preparation of novel cationic heterobimetallic ruthenium(ii)-gold(i) complexes that are highly cytotoxic to renal cancer Caki-1 and colon cancer HCT 116 cell lines while showing a synergistic effect and being more selective than their monometallic counterparts. PMID- 26804745 TI - Ultrasmall Magnetically Engineered Ag2Se Quantum Dots for Instant Efficient Labeling and Whole-Body High-Resolution Multimodal Real-Time Tracking of Cell Derived Microvesicles. AB - Cell-derived microvesicles (MVs) are natural carriers that can transport biological molecules between cells, which are expected to be promising delivery vehicles for therapeutic purposes. Strategies to label MVs are very important for investigation and application of MVs. Herein, ultrasmall Mn-magnetofunctionalized Ag2Se quantum dots (Ag2Se@Mn QDs) integrated with excellent near-infrared (NIR) fluorescence and magnetic resonance (MR) imaging capabilities have been developed for instant efficient labeling of MVs for their in vivo high-resolution dual-mode tracking. The Ag2Se@Mn QDs were fabricated by controlling the reaction of Mn(2+) with the Ag2Se nanocrystals having been pretreated in 80 degrees C NaOH solution, with an ultrasmall size of ca. 1.8 nm, water dispersibility, high NIR fluorescence quantum yield of 13.2%, and high longitudinal relaxivity of 12.87 mM(-1) s(-1) (almost four times that of the commercial contrast agent Gd-DTPA). The ultrasmall size of the Ag2Se@Mn QDs enables them to be directly and efficiently loaded into MVs by electroporation, instantly and reliably conferring both NIR fluorescence and MR traceability on MVs. Our method for labeling MVs of different origins is universal and free of unfavorable influence on intrinsic behaviors of MVs. The complementary imaging capabilities of the Ag2Se@Mn QDs have made the long-term noninvasive whole-body high-resolution dual-mode tracking of MVs in vivo realized, by which the dynamic biodistribution of MVs has been revealed in a real-time and in situ quantitative manner. This work not only opens a new window for labeling with QDs, but also facilitates greatly the investigation and application of MVs. PMID- 26804747 TI - Insights into cationic ordering in Re-based double perovskite oxides. AB - Cationic ordering in Sr2FeReO6 (SFRO) and Sr2CrReO6 (SCRO) is investigated using magnetic property measurement, atomic-scale imaging, and first-principles calculations. We find that the nature of cationic ordering strongly depends on the host oxides, although they have the same crystal symmetry and chemical formula. Firstly, adding Re is effective to enhance the cationic ordering in SFRO, but makes it worse in SCRO. Secondly, the microscopic structure of antisite (AS) defects, associated with the level of cationic ordering, is also distinguishable; the AS defects in SFRO are clustered in the form of an antiphase boundary-like feature, while they are randomly scattered in SCRO. Interestingly, we observe that the clustered AS defects deteriorate the ferromagnetism more than the scattered defects. Our findings elevate the importance of the AS defect configuration as well as the amount of defects in terms of magnetic property. PMID- 26804749 TI - Mucinous carcinoma of the breast: a comparative study on cytohistological findings associated with neuroendocrine differentiation. AB - OBJECTIVE: Mucinous carcinoma (MCA) may show neuroendocrine differentiation (ND), but the cytological features characteristic of ND remains elusive. We compared fine needle aspiration (FNA) findings of MCA between cases with high and low degrees of ND. METHODS: Histological sections of 37 MCA cases were immunohistochemically evaluated for expression of chromogranin A and synaptophysin, and were graded as 0 to 3+ degrees of ND. They were divided into low ND (grade 0 and 1+) and high ND (grade 2+ and 3+) groups. Pre-operative FNA samples of each group were assessed for cytological features. RESULTS: The mean age of the high ND group (n = 18) was higher than the low ND group (n = 19, P = 0.01). In FNA samples of the high ND group, 17 cases showed moderate to severe degrees of discohesiveness, but low ND cases mainly showed no or only mild discohesiveness (P < 0.001). Nine of the low ND cases displayed overlapped, cohesive cell clusters, whereas, in the high ND cases, the cells were arranged in a loose, flat and monolayered pattern (P = 0.045). Fourteen of the high ND cases had round nuclei, but oval nuclei were predominant in the low ND cases (P = 0.027). The nuclei were eccentrically located in 12 of the high ND cases but were centrally located in 14 of the low ND cases (P = 0.01). CONCLUSIONS: Mucinous carcinoma with high ND may be diagnosed by the presence of discohesiveness, a flat, monolayered pattern, and round or eccentrically located nuclei. Features of ND in carcinomas in other organs, such as intracytoplasmic granules and coarse chromatin, may not be reliable cytological features of ND in MCA. PMID- 26804750 TI - Variable speed wind turbine control by discrete-time sliding mode approach. AB - The aim of this paper is to propose a new design variable speed wind turbine control by discrete-time sliding mode approach. This methodology is designed for linear saturated system. The saturation constraint is reported on inputs vector. To this end, the back stepping design procedure is followed to construct a suitable sliding manifold that guarantees the attainment of a stabilization control objective. It is well known that the mechanisms are investigated in term of the most proposed assumptions to deal with the damping, shaft stiffness and inertia effect of the gear. The objectives are to synthesize robust controllers that maximize the energy extracted from wind, while reducing mechanical loads and rotor speed tracking combined with an electromagnetic torque. Simulation results of the proposed scheme are presented. PMID- 26804751 TI - Color Doppler Ultrasound Evaluation of Ureteral Jet Angle to Detect Vesicoureteral Reflux in Children. AB - PURPOSE: Vesicoureteral reflux is the most common urinary tract abnormality in children. Although voiding cystourethrography is the gold standard for diagnosing reflux, this approach is invasive. We evaluated color Doppler ultrasound measurement of ureteral jet angle as a noninvasive screening tool for detecting reflux. MATERIALS AND METHODS: We retrospectively evaluated 125 children (250 renal units) who presented with urinary tract infections or hydronephrosis. All patients underwent color Doppler ultrasonography and voiding cystourethrography. Ureteral jet angle was measured as angle between the direction of the ureteral jet and interureteral ridge. RESULTS: Reflux was diagnosed in 80 patients (117 renal units). Mean +/- SD ureteral jet angle was significantly greater in refluxing units (67.9 +/- 18.7 degrees) than in nonrefluxing units (47.8 +/- 17.3 degrees, p <0.0001). Angle value in each reflux grade became significantly greater according to grade (p <0.0001). Overall ability of ureteral jet angle to detect grade III to V and grade IV/V reflux, as given by the area under the receiver operating characteristic curve, was 0.81 and 0.88, respectively. A cutoff angle of 55 degrees or greater detected grade III to V and grade IV/V reflux with a sensitivity of 85.5% and 94.7%, respectively. A cutoff angle of 70 degrees or greater diagnosed grade IV/V reflux with a sensitivity of 81.6% and a specificity of 82.7%. CONCLUSIONS: Color Doppler ultrasound measurement of ureteral jet angle represents a simple and noninvasive method that is applicable as a screening tool to detect high grade vesicoureteral reflux in children. PMID- 26804752 TI - Safety and Efficacy of Ureteral Stent Placement at the Bedside Using Local Anesthesia. AB - PURPOSE: Ureteral stent placement for decompressing renal units obstructed by calculi is safe and can be potentially lifesaving in the prompt resolution of the sequelae of renal obstruction, infection and an obstructing stone. At many institutions there can be prolonged delay in getting patients to the operating room for stent placement. We hypothesized that it is safe and efficacious to attempt ureteral stent placement using local anesthesia at the bedside without live fluoroscopic guidance. MATERIALS AND METHODS: Patients presenting with symptomatic, obstructing ureteral calculi were given the option of bedside ureteral stent placement. Viscous lidocaine was placed into the urethra before flexible cystoscopic examination. A 260 cm Glidewire(r) was used as initial access with only 1 attempt at passage. All stent placements were confirmed with immediate post-procedure radiograph. Prospectively collected data were retrospectively analyzed for all patients who underwent attempted bedside ureteral stent placement. RESULTS: A total of 42 patients underwent attempted bedside stent placement under local anesthesia without fluoroscopic guidance. Mean stone size was 8.3 mm and 71% of stones were in the proximal ureter. Ureteral stent placement was pursued in 14% of patients for infection and in 59% for intractable pain. Ureteral stent placement was successful in 30 patients (71%). Statistical analysis did not reveal any significant predictors of successful stent placement in this cohort of patients. CONCLUSIONS: In our cohort bedside ureteral stent placement was well tolerated, safe and efficacious, thus expediting upper tract decompression in the setting of obstructed renal units in more than 70% of patients. PMID- 26804753 TI - Urethral Stricture Score is Associated with Anterior Urethroplasty Complexity and Outcome. AB - PURPOSE: Several surgical techniques are available to treat anterior urethral stricture. The choice of surgical technique largely depends on the severity of stricture disease. The U-score (urethral stricture score) is based on urethral stricture characteristics, namely length (1 to 3 points), number (1 or 2 points), location (1 or 2 points) and etiology (1 or 2 points), which are tallied to provide a total score of 4 to 9 points. Our aim was to identify whether the U score system is predictive of the surgical complexity and outcome of anterior urethroplasty. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients who underwent anterior urethroplasty from 2002 to 2012 by examining our prospectively collected urethroplasty database. We calculated the U-score and looked for an association with surgical complexity, recurrent stricture and time to recurrence. We defined recurrent stricture as the need for a secondary procedure. RESULTS: There were 341 patients who underwent low complexity urethroplasty (anastomotic, buccal mucosal graft and augmented anterior urethroplasty) with a mean U-score of 4.7 while 48 underwent high complexity urethroplasty (double buccal mucosal graft, flap and graft/flap combination) with a mean score of 6.9. Higher U-score was predictive of higher surgical complexity (p <0.001). U-score was also significantly associated with recurrence. There was a consistent increase in the risk of recurrence with each additional U-score point. However, there was no association of U-score with time to recurrence. CONCLUSIONS: We confirmed the validity of U-score to predict the complexity of surgery for anterior urethral strictures. For the first time to our knowledge we report an association between higher U-score and anterior urethroplasty outcome. The U-score could be used to risk stratify patients and help with perioperative counseling. PMID- 26804754 TI - Early Intervention during Acute Stone Admissions: Revealing "The Weekend Effect" in Urological Practice. AB - PURPOSE: Obstructing nephrolithiasis is a common condition that can require urgent intervention. In this study we analyze patient factors that contribute to delayed intervention during acute stone admission. MATERIALS AND METHODS: We retrospectively reviewed the HCUP SID (Healthcare Cost and Utilization Project State Inpatient Database) for Florida and California from 2007 to 2011. Patients who were admitted urgently with nephrolithiasis and an indication for decompression (urinary tract infection, acute renal insufficiency and/or sepsis) were included in the study. Intervention was timely or delayed, defined as a procedure that occurred within or after 48 hours, respectively. Adjusted multivariate models were fit to assess factors that predicted a delayed procedure as well as mortality. RESULTS: Overall 10,301 patients were admitted urgently for nephrolithiasis with indications for decompression. Early intervention occurred in 6,689 patients (65%) and was associated with a decrease in mortality (11, 0.16%), compared to delayed intervention (17 of 3,612, 0.47%, p=0.002). On multivariate analysis timely intervention significantly decreased the odds of inpatient mortality (OR 0.43, p=0.044). Weekend day admission significantly influenced time to intervention, decreasing patient odds of timely intervention by 26% (p <0.001). Other factors decreasing patient odds of timely intervention included nonCaucasian race and nonprivate insurance. Presenting medical diagnoses of urinary tract infection, sepsis and acute renal failure did not appear to influence time to intervention. CONCLUSIONS: Delayed operative intervention for acute nephrolithiasis admissions with indications for decompression results in increased patient mortality. Nonmedical factors such as the "weekend effect," race and insurance provider exerted the greatest influence on the timing of intervention. PMID- 26804755 TI - Prostate Cancer Expression Profiles of Cytoplasmic ERbeta1 and Nuclear ERbeta2 are Associated with Poor Outcomes following Radical Prostatectomy. AB - PURPOSE: Existing data regarding the expression of estrogen receptors (ERs) and prostate cancer outcomes have been limited. We evaluated the relationship of expression profiles of ERbeta subtypes and the ER GPR30 (G-protein-coupled receptor-30) with patient factors at diagnosis and outcomes following radical prostatectomy. MATERIALS AND METHODS: Tissue microarrays constructed using samples from 566 men with long-term clinical followup were analyzed by immunohistochemistry targeting ERbeta1, ERbeta2, ERbeta5 and GPR30. An experienced pathologist scored receptor distribution and staining intensity. Tumor staining characteristics were evaluated for associations with patient characteristics, recurrence-free survival and prostate cancer specific mortality following radical prostatectomy. RESULTS: Prostate cancer cells had unique receptor subtype staining patterns. ERbeta1 demonstrated predominantly nuclear localization while ERbeta2, ERbeta5 and GPR30 were predominantly cytoplasmic. After controlling for patient factors intense cytoplasmic ERbeta1 staining was independently associated with time to recurrence (HR 1.7, 95% CI 1.1-2.6, p = 0.01) and prostate cancer specific mortality (HR 6.6, 95% CI 1.8-24.9, p = 0.01). Intense nuclear ERbeta2 staining was similarly independently associated with prostate cancer specific mortality (HR 3.9, 95% CI 1.1-13.4, p = 0.03). Patients with cytoplasmic ERbeta1 and nuclear ERbeta2 co-staining had significantly worse 15-year prostate cancer specific mortality than patients with expression of only cytoplasmic ERbeta1, only nuclear ERbeta2 and neither ER (16.4%, 4.3%, 0.0% and 2.0 %, respectively, p = 0.001). CONCLUSIONS: Increased cytoplasmic ERbeta1 and nuclear ERbeta2 expression is associated with worse cancer specific outcomes following radical prostatectomy. These findings suggest that tumor ERbeta1 and ERbeta2 staining patterns provide prognostic information on patients treated with radical prostatectomy. PMID- 26804756 TI - Current Paradigm for Ischemia in Kidney Surgery. AB - PURPOSE: Partial nephrectomy is the accepted standard of care for treatment of patients with small renal masses. The primary goal while performing partial nephrectomy is cancer control with a secondary important goal of maximizing renal function preservation with minimal perioperative morbidity. Recent studies have highlighted the importance of renal parenchymal quality and quantity postoperatively rather than duration of ischemia in determining long-term renal function. We review the available data regarding perioperative renal function optimization with special interest in ischemia during partial nephrectomy, highlighting the controversies and establishing future lines of investigation. MATERIALS AND METHODS: We performed a comprehensive literature review for the years 1970 to 2014 via MEDLINE((r)), PubMed((r)) and the Cochrane Library. Review was consistent with the PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) criteria. We used MeSH (Medical Subject Headings) terms for the search including "acute kidney injury/failure," "carcinoma, renal cell/carcinoma of kidney/neoplasm of kidney," "kidney failure, chronic/end-stage kidney disease," "ischemia-reperfusion" and "warm ischemia/cold ischemia." Relevant review articles were included. Abstracts from major urological/surgical conferences were reviewed. All studies included were performed in adults, were written in English and had an abstract available. RESULTS: Our traditional knowledge of renal ischemia is derived from animal studies, ie kidney transplant and retrospective partial nephrectomy series that indicate the risk of renal function impairment for every minute of ischemia. Careful evaluation of historical studies highlights flaws of the use of ischemia duration as a dichotomous marker (25 or 30 minutes) while predicting renal function outcomes. Recent studies have revealed no effect of duration of ischemia on ultimate kidney function in the short or long term. Quality and quantity of parenchyma preserved postoperatively are key predictors of ultimate renal function after partial nephrectomy. Traditionally partial nephrectomy has been performed with hilar occlusion to provide a relatively bloodless surgical field allowing effective oncologic control during tumor excision with secure management of blood vessels, collecting system and renal reconstruction. Selective clamping and nonclamping techniques have been proposed to avoid the perceived harmful effects of ischemia, although they convert a complex surgery into a more challenging procedure, potentially limiting the widespread use of partial nephrectomy for management of renal cancers. Promising urine and blood-based biomarkers (NGAL, KIM-1) in the context of critical care settings and global stress have been observed to predict acute kidney injury. Within the partial nephrectomy environment the usefulness of those markers needs to be further investigated. To date, no study has proved their usefulness in the setting of partial nephrectomy. CONCLUSIONS: Based on the available evidence, use of a single cutoff for duration of ischemia time as a dichotomous value for renal function outcomes in the setting of partial nephrectomy is flawed. Renal ischemia is a controversial topic with a shifted paradigm within the last decade. Current evidence has shown that patients with 2 kidneys undergoing nephron sparing surgery can tolerate ischemia times of more than 30 minutes without a clinically significant decline in renal function. Biomarkers predictive of renal tubular injury fail to predict acute kidney injury in the context of partial nephrectomy. Indications for partial nephrectomy could be significantly expanded as the safety of limited renal ischemia is now better understood. PMID- 26804757 TI - Secreted autoantibody repertoires in Sjogren's syndrome and systemic lupus erythematosus: A proteomic approach. AB - The structures of epitopes bound by autoantibodies against RNA-protein complexes have been well-defined over several decades, but little is known of the clonality, immunoglobulin (Ig) variable (V) gene usage and mutational status of the autoantibodies themselves at the level of the secreted (serum) proteome. A novel proteomic workflow is presented based on affinity purification of specific Igs from serum, high-resolution two-dimensional gel electrophoresis, and de novo and database-driven sequencing of V-region proteins by mass spectrometry. Analysis of anti-Ro52/Ro60/La proteomes in primary Sjogren's syndrome (SS) and anti-Sm and anti-ribosomal P proteomes in systemic lupus erythematosus (SLE) has revealed that these antibody responses are dominated by restricted sets of public (shared) clonotypes, consistent with common pathways of production across unrelated individuals. The discovery of shared sets of specific V-region peptides can be exploited for diagnostic biomarkers in targeted mass spectrometry platforms and for tracking and removal of pathogenic clones. PMID- 26804759 TI - Genetic aspects of the antiphospholipid syndrome: An update. AB - Studies on the immunogenetic predisposition to antiphospholipid syndrome (APS) and on other non-genetic and epigenetic factors are summarised and discussed. Family studies suggest a genetic predisposition to APS. It appears that this genetic predisposition is in part accounted for by the HLA system, the most consistent associations being those with DR4 and DRw53. Furthermore, it appears that lupus anticoagulant (LA) and anticardiolipin (aCL) antibodies are both associated with the same HLA antigens. Population studies suggest that HLA genes have a role in conferring susceptibility to develop primary APS, with some differences in different ethnic groups. Other genes, outside the MHC, give their contribution to the development of this autoimmune syndrome, such as IRF5, STAT4 and those related to inherited thrombophilia--factor V Leiden and G20210A prothrombin polymorphisms. Finally, post-transcriptional modifications of anti beta2GPI antibodies could be implicated too. PMID- 26804758 TI - The role of IL-17 in vitiligo: A review. AB - IL-17 is involved in the pathogenesis of several autoimmune diseases; however its role in vitiligo has not been well defined. Emerging human and mouse studies have demonstrated that systemic, tissue, and cellular levels of IL-17 are elevated in vitiligo. Many studies have also shown significant positive correlations between these levels and disease activity, extent, and severity. Treatments that improve vitiligo, such as ultraviolet B phototherapy, also modulate IL-17 levels. This review synthesizes our current understanding of how IL-17 may influence the pathogenesis of autoimmune vitiligo at the molecular level. This has implications for defining new vitiligo biomarkers and treatments. PMID- 26804760 TI - Office-Based Cataract Surgery: Population Health Outcomes Study of More than 21 000 Cases in the United States. AB - PURPOSE: To identify safety and effectiveness outcomes of office-based cataract surgery. Each year, approximately 3.7 million cataract surgeries in the United States are performed in Ambulatory Surgery Center (ASC) and Hospital Outpatient Department (HOPD) locations. Medicare in July 2015 published a solicitation for expert opinion on reimbursing office-based cataract surgery. DESIGN: Large-scale, retrospective, consecutive case series of cataract surgeries performed in Minor Procedure Rooms (MPRs) of a large US integrated healthcare center. PARTICIPANTS: More than 13 500 patients undergoing elective office-based cataract surgery. METHODS: Phacoemulsification cataract surgery performed in MPRs of Kaiser Permanente Colorado from 2011 to 2014. MAIN OUTCOME MEASURES: Postoperative visual acuity and intraoperative and postoperative adverse events (AEs). RESULTS: Office-based cataract surgery was completed in 21 501 eyes (13 507 patients, age 72.6+/-9.6 years). Phacoemulsification was performed in 99.9% of cases, and manual extracapsular extraction was performed in 0.1% of cases. Systemic comorbidities included hypertension (53.5%), diabetes (22.3%), and chronic obstructive pulmonary disease (9.4%). Postoperative mean best-corrected visual acuity measured 0.14+/-0.26 logarithm of the minimum angle of resolution units. Intraoperative ocular AEs included 119 (0.55%) cases of capsular tear and 73 (0.34%) cases of vitreous loss. Postoperative AEs included iritis (n = 330, 1.53%), corneal edema (n = 110, 0.53%), and retinal tear or detachment (n = 30, 0.14%). No endophthalmitis was reported. Second surgeries were performed in 0.70% of treated eyes within 6 months. There were no life- or vision-threatening intraoperative or perioperative AEs. CONCLUSIONS: This is the largest US study to investigate the safety and effectiveness of office-based cataract surgery performed in MPRs. Office-based efficacy outcomes were consistently excellent, with a safety profile expected of minimally invasive cataract procedures performed in ASCs and HOPDs. PMID- 26804761 TI - Treatment of Presbyopia in Emmetropes Using a Shape-Changing Corneal Inlay: One Year Clinical Outcomes. AB - PURPOSE: To report 1-year safety and efficacy clinical outcomes of a shape changing corneal inlay for the treatment of presbyopia. DESIGN: Prospective, nonrandomized, multicenter United States Food and Drug Administration Investigational Device Exemption clinical trial (clinicaltrials.gov identifier, NCT01373580). PARTICIPANTS: Nondominant eyes (N = 373) of emmetropic presbyopic subjects were implanted at 11 sites with the Raindrop Near Vision Inlay (ReVision Optics, Lake Forest, CA); 340 eyes underwent the 1-year follow-up visit. METHODS: The corneal inlay was implanted under a corneal flap at the center of the light constricted pupil created with a femtosecond laser. MAIN OUTCOME MEASURES: For subjects completing the 1-year follow-up, monocular and binocular uncorrected and corrected visual acuity, refractive stability, contrast sensitivity (CS; photopic and mesopic), symptom and satisfaction questionnaire results, and adverse events. RESULTS: At 1 year in the treated eye, on average, uncorrected near visual acuity (UNVA) improved by 5.1 lines, uncorrected intermediate visual acuity (UIVA) improved by 2.5 lines, and uncorrected distance visual acuity (UDVA) decreased by 1.2 lines. From 3 months through 1 year, 93% of subjects achieved UNVA of 20/25 or better, 97% achieve UIVA of 20/32 or better, and 95% achieved UDVA of 20/40 or better. Binocularly, the mean UDVA exceeded 20/20 from 3 months through 1 year. Contrast sensitivity loss occurred only at the highest spatial frequencies, with no loss binocularly. Absent or mild scores were reported in 96% of subjects for visual symptoms (glare, halos, double vision, and fluctuations in vision), in 99% for ocular symptoms (pain, light sensitivity, and discomfort), and in 95% for dryness. Adverse events were treatable and resolved. Eighteen inlays were replaced, usually soon after implantation because of decentration, but UNVA was little affected in this group thereafter. In the 11 cases requiring inlay explantations, 100% achieved a corrected distance visual acuity of 20/25 or better by 3 months after explant. CONCLUSIONS: The Raindrop Near Vision Inlay provides significant improvement in near and intermediate visual performance, with no significant change in binocular distance vision or CS. Subject satisfaction is improved significantly with minimal ocular or visual symptoms. PMID- 26804764 TI - 4-Nonylphenol induces apoptosis, autophagy and necrosis in Sertoli cells: Involvement of ROS-mediated AMPK/AKT-mTOR and JNK pathways. AB - The xenoestrogen 4-nonylphenol (NP) induces reproductive dysfunction of male rats, but the fundamental mechanism of this phenomenon is largely unexplored. Sertoli cells (SCs) are pivotal for spermatogenesis and male fertility. The involvement of autophagy in NP-induced apoptotic and necrotic death of SCs was investigated. In this study, 24-h exposure of SCs to 20-30MUM NP decreased cell viability, caused G2/M arrest, triggered DeltaPsim loss, increased ROS production and induced caspase-dependent apoptosis, necrosis as well as autophagosome formation. NP-induced autophagy was confirmed by monodansylcadaverine-staining and LC3-I/LC3-II conversion. Furthermore, NP up-regulated the (Thr172)p-AMPK/AMPK and (Thr183/185)p-JNK/JNK ratios. This was followed by the down-regulation of (Ser473)p-Akt/Akt, (Thr1462)p-TSC2/TSC2, (Ser2448)p-mTOR/mTOR, (Thr389)p p70S6K/p70S6K and (Thr37/45)p-4EBP1/4EBP1. Intriguingly, NP-induced apoptosis, autophagy and necrosis could be inhibited through blocking ROS generation by N acetylcysteine. Autophagy inhibitor 3-MA enhanced NP-induced apoptosis and necrosis. Moreover, The activation of AMPK/mTOR/p70s6k/4EBP1 and JNK signalling pathways induced by NP could be efficiently reversed by pretreatment of N acetylcysteine or 3-MA. Collectively, our findings provide the first evidence that NP promotes apoptosis, autophagy and necrosis simultaneously in SCs and that this process may involve ROS-dependent JNK- and Akt/AMPK/mTOR pathways. Modulation of autophagy induced by NP may serve as a survival mechanism against apoptosis and necrosis. PMID- 26804765 TI - The cooperative FeCl3/DDQ system for the regioselective synthesis of 3 arylindoles from beta-monosubstituted 2-alkenylanilines. AB - A highly regioselective synthesis of 3-arylindoles by using the cooperative FeCl3/DDQ system has been developed. This new protocol represents an attractive route for the synthesis of 3-arylindoles from readily accessible non-indole precursors, beta-aryl-substituted 2-styrylanilines, using an inexpensive catalyst and oxidant. Noteworthy is the unique synergetic and synergistic effect of FeCl3 and DDQ on the 1,2-aryl migratory process. PMID- 26804762 TI - Interventions for Age-Related Macular Degeneration: Are Practice Guidelines Based on Systematic Reviews? AB - PURPOSE: Are existing systematic reviews of interventions for age-related macular degeneration incorporated into clinical practice guidelines? DESIGN: High-quality systematic reviews should be used to underpin evidence-based clinical practice guidelines and clinical care. We examined the reliability of systematic reviews of interventions for age-related macular degeneration (AMD) and described the main findings of reliable reviews in relation to clinical practice guidelines. METHODS: Eligible publications were systematic reviews of the effectiveness of treatment interventions for AMD. We searched a database of systematic reviews in eyes and vision without language or date restrictions; the database was up to date as of May 6, 2014. Two authors independently screened records for eligibility and abstracted and assessed the characteristics and methods of each review. We classified reviews as reliable when they reported eligibility criteria, comprehensive searches, methodologic quality of included studies, appropriate statistical methods for meta-analysis, and conclusions based on results. We mapped treatment recommendations from the American Academy of Ophthalmology (AAO) Preferred Practice Patterns (PPPs) for AMD to systematic reviews and citations of reliable systematic reviews to support each treatment recommendation. RESULTS: Of 1570 systematic reviews in our database, 47 met inclusion criteria; most targeted neovascular AMD and investigated anti-vascular endothelial growth factor (VEGF) interventions, dietary supplements, or photodynamic therapy. We classified 33 (70%) reviews as reliable. The quality of reporting varied, with criteria for reliable reporting met more often by Cochrane reviews and reviews whose authors disclosed conflicts of interest. Anti-VEGF agents and photodynamic therapy were the only interventions identified as effective by reliable reviews. Of 35 treatment recommendations extracted from the PPPs, 15 could have been supported with reliable systematic reviews; however, only 1 recommendation cited a reliable intervention systematic review. No reliable systematic review was identified for 20 treatment recommendations, highlighting areas of evidence gaps. CONCLUSIONS: For AMD, reliable systematic reviews exist for many treatment recommendations in the AAO PPPs and should be cited to support these recommendations. We also identified areas where no high level evidence exists. Mapping clinical practice guidelines to existing systematic reviews is one way to highlight areas where evidence generation or evidence synthesis is either available or needed. PMID- 26804766 TI - Distribution of clinical events across platelet aggregation values in all-comers treated with prasugrel and ticagrelor. AB - The aim of this study was to investigate the distribution of clinical events across the platelet aggregation values in patients treated with prasugrel and ticagrelor. This prospective observational study enrolled 226 patients treated with prasugrel (n=121) or ticagrelor (n=105). Adenosine diphosphate (ADP)-induced platelet aggregation was determined by Multiplate Analyzer in the maintenance phase of treatment with prasugrel or ticagrelor. Clinical outcome was evaluated over 12 months. Platelet aggregation values were divided into quartiles. The first quartile comprised values <8 U, the second quartile values between 8 U and <15 U, the third one values between 15 U and 23 U, and the forth one values >23 U. Myocardial infarction events were observed in patients within the third quartile of aggregation values (15-23 U), and were not associated with high on treatment platelet reactivity (HTPR>46 U). All bleeding events occurred in patients with aggregation values <= 23 U, which corresponded to the 75 percentile (p=0.031). There was no difference in the distribution of bleeding events between the 1st-3rd quartiles (p=0.873). In conclusion, patients with ADP-induced aggregation values over 23 U (fourth quartile) were at the lowest risk to develop bleeding during the follow-up. PMID- 26804768 TI - [Works awarded at the 55th Chilean Paediatrics Congress, Puerto Varas, Chile, October 2015]. PMID- 26804769 TI - Identification of protective components that prevent the exacerbation of goose fatty liver: Characterization, expression and regulation of adiponectin receptors. AB - Fat accumulation in the liver is a natural process in goose, which prepares goose for long-distance migration. In contrast to mammalian fatty liver that usually progresses into an irreversible status, steatohepatitis, goose fatty liver can return to normal without obvious pathological damage, suggesting a protective system exists in goose liver. This study was to identify the components of this system. We first focused on goose adiponectin receptor 1 and 2 (Adipor1/2) as they have ceramidase activity, and can cleave ceramide, a group of proinflammatory signaling lipid species. Quantitative analysis indicated that tumor necrosis factor alpha (Tnfalpha), a key proinflammatory cytokine, was down regulated in goose fatty liver by overfeeding. This inhibition of Tnfalpha was accompanied with reduced adiponectin and increased Adipor1/2 in the adipose tissues and in the livers of the overfed geese, respectively. To investigate the regulation of goose Adipor2 in the context of fatty liver, we treated goose primary hepatocytes with fatty liver associated factors. Data indicated that Adipor2 was upregulated by glucose and oleate but not palmitate. Its expression was even suppressed by high level of insulin. The regulation of Adipor1 by these factors was quite similar to that of Adipor2 except that glucose did not induce Adipor1. Together, these findings suggest the upregulation of Adipor1/2 may, at least partially, contribute to the inhibition of inflammation in goose fatty liver, and the expression of Adipor1/2 can be regulated by fatty liver-associated factors. PMID- 26804770 TI - Exponential decay of spatial correlation in driven diffusive system: A universal feature of macroscopic homogeneous state. AB - Driven diffusive systems have been a paradigm for modelling many physical, chemical, and biological transport processes. In the systems, spatial correlation plays an important role in the emergence of a variety of nonequilibrium phenomena and exhibits rich features such as pronounced oscillations. However, the lack of analytical results of spatial correlation precludes us from fully understanding the effect of spatial correlation on the dynamics of the system. Here we offer precise analytical predictions of the spatial correlation in a typical driven diffusive system, namely facilitated asymmetric exclusion process. We find theoretically that the correlation between two sites decays exponentially as their distance increases, which is in good agreement with numerical simulations. Furthermore, we find the exponential decay is a universal property of macroscopic homogeneous state in a broad class of 1D driven diffusive systems. Our findings deepen the understanding of many nonequilibrium phenomena resulting from spatial correlation in driven diffusive systems. PMID- 26804771 TI - Protective coatings for intraocular wirelessly controlled microrobots for implantation: Corrosion, cell culture, and in vivo animal tests. AB - Diseases in the ocular posterior segment are a leading cause of blindness. The surgical skills required to treat them are at the limits of human manipulation ability, and involve the risk of permanent retinal damage. Instrument tethering and design limit accessibility within the eye. Wireless microrobots suturelessly injected into the posterior segment, steered using magnetic manipulation are proposed for procedures involving implantation. Biocompatibility is a prerequisite for these procedures. This article investigates the use of polypyrrole- and gold-coated cobalt-nickel microrobots. While gold has been used in ocular implants, no ocular implantation involving polypyrrole is reported, despite its well-established biocompatibility properties. Coated and uncoated microrobots were investigated for their corrosion properties, and solutions that had contained coated and uncoated microrobots for one week were tested for cytotoxicity by monitoring NIH3T3 cell viability. None of the microrobots showed significant corrosion currents and corrosion potentials were as expected in relation to the intrinsic nobility of the materials. NIH3T3 cell viability was not affected by the release medium, in which coated/uncoated microrobots were stored. In vivo tests inside rabbit eyes were performed using coated microrobots. There were no significant inflammatory responses during the first week after injection. An inflammatory response detected after 2 weeks was likely due to a lack of longer-duration biocompatibility. The results provide valuable information for those who work on implant technology and biocompatibility. Coated microrobots have the potential to facilitate a new generation of surgical treatments, diagnostics and drug-delivery techniques, when implantation in the ocular posterior segment will be possible. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 836-845, 2017. PMID- 26804772 TI - Prevalence and relevance of Type D personality in fibromyalgia. AB - OBJECTIVE: Distressed (Type D) personality, combining high negative affectivity and social inhibition, is linked to poor health in various populations. Because patients with fibromyalgia experience high negative affect and show signs of social inhibition, this study aimed to examine the prevalence of Type D's components and their associations with health in an additive (worse health with both components present) or synergistic way (components amplifying each other's effects). METHOD: Type D personality and physical and mental health were assessed online by 558 patients with self-reported fibromyalgia (94% women, age 47 +/- 11 (21-77)years) by the Type D Scale-14 and RAND-36 Health Status Inventory. RESULTS: Using the standard cutscores, Type D personality was present in 56.5% of patients. Negative affectivity alone and combined with social inhibition was associated with worse mental and, more limited, physical health, but no interactive (synergistic) associations were found. CONCLUSIONS: Type D personality in fibromyalgia exceeds prevalence estimates in general, cardiovascular and chronic pain populations. Some indication of an additive but not of a synergistic effect was found, particularly for mental health, with clearly the largest associations for negative affectivity. The high prevalence of Type D's components may have specific treatment implications. PMID- 26804773 TI - Factors related to suicidal behavior in patients with bipolar disorder: the effect of mixed features on suicidality. AB - OBJECTIVES: The aim of the present study was to investigate various risk factors of suicidal behaviors, including the mixed features specifier, in patients with bipolar disorder. METHODS: We retrospectively reviewed medical charts from 2005 to 2014. A total of 334 patients diagnosed with bipolar disorder using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision were enrolled. Subjects were categorized into two groups according to their history of suicidal behavior and the demographic and clinical characteristics of the groups were compared, including the mixed features specifier. We reevaluated the index episode using Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria and classified subjects into an index episode with mixed features group and an index episode without mixed features group. Logistic regression was performed to evaluate significant risk factors associated with suicidal behavior. RESULTS: Suicidal behavior had an independent relationship to mixed features at the index episode using DSM-5 criteria [odds ratio (OR)=3.39; 95% confidence interval (CI): 1.57 7.34] and number of previous depressive episodes (OR=1.62; 95% CI: 1.34-1.95) in bipolar patients. The mixed feature specifier was the strongest risk factor for suicidal behavior in the present study. CONCLUSIONS: This study may help clinicians understand potential risk factors and manage bipolar disorders with suicidal behaviors. Clinicians should carefully monitor patients with bipolar disorder who exhibit numerous depressive episodes or mixed features for suicidal behavior. PMID- 26804774 TI - Current depressive symptoms but not history of depression predict hospital readmission or death after discharge from medical wards: a multisite prospective cohort study. AB - OBJECTIVE: Although death or readmission shortly after hospital discharge is frequent, identifying inpatients at higher risk is difficult. We evaluated whether in-hospital depressive symptoms (hereafter "depression") are associated with short-term readmission or mortality after discharge from medical wards. METHODS: Depression was assessed at discharge in a prospective inpatient cohort from 2 Canadian hospitals (7 medical wards) and defined as scores >= 11 on the 27 point Patient Health Questionnaire (PHQ-9). Primary outcome was all-cause readmission or mortality 90 days postdischarge. RESULTS: Of 495 medical patients [median age 64 years, 51% women, top 3 admitting diagnoses heart failure (10%), pneumonia (10%) and chronic obstructive pulmonary disease (8%)], 127 (26%) screened positive for depression at discharge. Compared with nondepressed patients, those with depression were more frequently readmitted or died: 27/127 (21%) vs. 58/368 (16%) within 30 days and 46 (36%) vs. 91 (25%) within 90 days [adjusted odds ratio (aOR) 2.00, 95% confidence interval 1.25-3.17, P=.004, adjusted for age, sex and readmission/death prediction scores]. History of depression did not predict 90-day events (aOR 1.05, 95% CI 0.64-1.72, P=.84). Depression persisted in 40% of patients at 30 days and 17% at 90 days. CONCLUSIONS: Depression was common, underrecognized and often persisted postdischarge. Current symptoms of depression, but not history, identified greater risk of short-term events independent of current risk prediction rules. PMID- 26804775 TI - Pre- and post-discharge factors influencing early readmission to acute psychiatric wards: implications for quality-of-care indicators in psychiatry. AB - OBJECTIVE: This study aims to describe the association between pre- and post discharge factors and early readmission to acute psychiatric wards in a well integrated community-based psychiatric service. METHODS: The analysis consisted of all the hospital discharge records containing a psychiatric diagnosis in 2011 from four Italian acute inpatient wards. Socio-demographic, clinical, admission and aftercare variables were investigated as possible predictors of readmission at 7, 30 and 90 days after discharge and were analyzed, controlling for dependency among same-patient observations. RESULTS: Previous psychiatric history was the most important predictor of readmissions. The socio-demographic and clinical characteristics of patients did not clearly influence readmission. Length of stay (LoS) was significant for readmission at 7 days even after controlling for other predictors and for same-patient dependence, in particular, for patients with previous admissions. Results suggest a protective role of a LoS higher than 28 days. In general, having a contact in community services did not turn out as protective from early readmission. CONCLUSIONS: This paper contributes to increase the knowledge about factors that may predict the risk of early readmission. Implications for quality assessment in psychiatry emerged: readmission seems actionable by LoS and not by community follow-up. PMID- 26804776 TI - Biochemical and molecular changes in rice seedlings (Oryza sativa L.) to cope with chromium stress. AB - Chromium (Cr) is very toxic to both humans and plants. This investigation aimed to understand the physiological and molecular responses of rice seedlings to Cr stress. Cr toxicity did not significantly affect morphological features and Cr accumulation in roots and shoots in Pokkali but not in BRRI 51, although there was a reduction in chlorophyll concentration in leaves of both genotypes. These results imply that Pokkali has mechanisms to cope with Cr supplementation. We therefore performed quantitative real-time PCR on the expression pattern of two chelator genes, OsPCS1 and OsMT1, but there were no significant changes in expression in roots and shoots of Pokkali and BRRI 51 following Cr stress. This suggests that there was no metal sequestration following heavy metal stress in roots of these genotypes. Moreover, no expression of two heavy metal transporter genes, OsHMA3 and OsNRAMP1, was induced after Cr stress in roots and shoots, suggesting that these transporter genes are not induced by Cr stress or might not be involved in Cr uptake in rice. We also performed a targeted study on the effect of Cr on Fe uptake mechanisms. Our studies showed a consistent reduction in Fe uptake, Fe reductase activity and expression of Fe-related genes (OsFRO1 and OsIRT1) under Cr stress in both roots and leaves of Pokkali. In contrast, these parameters and genes were significantly increased in Cr-sensitive BRRI 51 under Cr stress. The results confirm that limiting Fe uptake through the down regulation of Fe reductase and Fe transporter genes is the main strategy of Cr tolerant Pokkali to cope with Cr stress. Finally, increased CAT, POD and GR activity and elevated glutathione and proline synthesis might provide strong antioxidant defence against Cr stress in Pokkali. Taken together, our findings reveal that Cr stress tolerance in rice (Pokkali) is not related to metal sequestration but is associated with reduced Fe transport and increased antioxidant defence. PMID- 26804777 TI - Distinctive injury deaths: the role of environment, policy and measurement across states. AB - BACKGROUND: Maps identifying the most distinctive feature of each state have become popular on social media, but may also have important public health applications. A map identifying the most distinctive injury death in each state could be a useful tool for policymakers, enabling them to identify potential gaps in prevention efforts. OBJECTIVE: To identify the most distinctive cause of injury death in each state and explore potential reasons for the geographical variation. METHODS: The Centers for Disease Control Web-based Injury Statistics Query and Reporting System was used to identify the injury death for each state with a rate which was the largest multiple of the national rate. Analyses were conducted with and without inclusion of 'indefinite' codes, which include injury causes of death of undetermined intent, unspecified person killed in a motor vehicle crash (MVC; vehicle occupant, cyclist, pedestrian, etc) or unspecified injury. RESULTS: Noteworthy patterns included seven states in Appalachia and the Southeast with high relative rates of unintentional firearm deaths (2.14-4.06 times the national average) and five states on the West Coast with high relative rates of legal intervention deaths (1.76-3.49 times the national average). Sensitivity analyses indicated that use of 'undetermined intent' classifications and the level of detail in coding MVCs vary substantially by state. CONCLUSIONS: These analyses highlight potential areas for prevention, such as promotion of safe storage laws in states with relatively high rates of unintentional firearm deaths and areas where standardisation of cause of death codes could be improved. PMID- 26804779 TI - Training shortest-path tractography: Automatic learning of spatial priors. AB - Tractography is the standard tool for automatic delineation of white matter tracts from diffusion weighted images. However, the output of tractography often requires post-processing to remove false positives and ensure a robust delineation of the studied tract, and this demands expert prior knowledge. Here we demonstrate how such prior knowledge, or indeed any prior spatial information, can be automatically incorporated into a shortest-path tractography approach to produce more robust results. We describe how such a prior can be automatically generated (learned) from a population, and we demonstrate that our framework also retains support for conventional interactive constraints such as waypoint regions. We apply our approach to the open access, high quality Human Connectome Project data, as well as a dataset acquired on a typical clinical scanner. Our results show that the use of a learned prior substantially increases the overlap of tractography output with a reference atlas on both populations, and this is confirmed by visual inspection. Furthermore, we demonstrate how a prior learned on the high quality dataset significantly increases the overlap with the reference for the more typical yet lower quality data acquired on a clinical scanner. We hope that such automatic incorporation of prior knowledge and the obviation of expert interactive tract delineation on every subject, will improve the feasibility of large clinical tractography studies. PMID- 26804780 TI - The LDA beamformer: Optimal estimation of ERP source time series using linear discriminant analysis. AB - We introduce a novel beamforming approach for estimating event-related potential (ERP) source time series based on regularized linear discriminant analysis (LDA). The optimization problems in LDA and linearly-constrained minimum-variance (LCMV) beamformers are formally equivalent. The approaches differ in that, in LCMV beamformers, the spatial patterns are derived from a source model, whereas in an LDA beamformer the spatial patterns are derived directly from the data (i.e., the ERP peak). Using a formal proof and MEG simulations, we show that the LDA beamformer is robust to correlated sources and offers a higher signal-to-noise ratio than the LCMV beamformer and PCA. As an application, we use EEG data from an oddball experiment to show how the LDA beamformer can be harnessed to detect single-trial ERP latencies and estimate connectivity between ERP sources. Concluding, the LDA beamformer optimally reconstructs ERP sources by maximizing the ERP signal-to-noise ratio. Hence, it is a highly suited tool for analyzing ERP source time series, particularly in EEG/MEG studies wherein a source model is not available. PMID- 26804778 TI - The Automatic Neuroscientist: A framework for optimizing experimental design with closed-loop real-time fMRI. AB - Functional neuroimaging typically explores how a particular task activates a set of brain regions. Importantly though, the same neural system can be activated by inherently different tasks. To date, there is no approach available that systematically explores whether and how distinct tasks probe the same neural system. Here, we propose and validate an alternative framework, the Automatic Neuroscientist, which turns the standard fMRI approach on its head. We use real time fMRI in combination with modern machine-learning techniques to automatically design the optimal experiment to evoke a desired target brain state. In this work, we present two proof-of-principle studies involving perceptual stimuli. In both studies optimization algorithms of varying complexity were employed; the first involved a stochastic approximation method while the second incorporated a more sophisticated Bayesian optimization technique. In the first study, we achieved convergence for the hypothesized optimum in 11 out of 14 runs in less than 10 min. Results of the second study showed how our closed-loop framework accurately and with high efficiency estimated the underlying relationship between stimuli and neural responses for each subject in one to two runs: with each run lasting 6.3 min. Moreover, we demonstrate that using only the first run produced a reliable solution at a group-level. Supporting simulation analyses provided evidence on the robustness of the Bayesian optimization approach for scenarios with low contrast-to-noise ratio. This framework is generalizable to numerous applications, ranging from optimizing stimuli in neuroimaging pilot studies to tailoring clinical rehabilitation therapy to patients and can be used with multiple imaging modalities in humans and animals. PMID- 26804781 TI - Comparison of 3D orientation distribution functions measured with confocal microscopy and diffusion MRI. AB - The ability of diffusion MRI (dMRI) fiber tractography to non-invasively map three-dimensional (3D) anatomical networks in the human brain has made it a valuable tool in both clinical and research settings. However, there are many assumptions inherent to any tractography algorithm that can limit the accuracy of the reconstructed fiber tracts. Among them is the assumption that the diffusion weighted images accurately reflect the underlying fiber orientation distribution (FOD) in the MRI voxel. Consequently, validating dMRI's ability to assess the underlying fiber orientation in each voxel is critical for its use as a biomedical tool. Here, using post-mortem histology and confocal microscopy, we present a method to perform histological validation of orientation functions in 3D, which has previously been limited to two-dimensional analysis of tissue sections. We demonstrate the ability to extract the 3D FOD from confocal z stacks, and quantify the agreement between the MRI estimates of orientation information obtained using constrained spherical deconvolution (CSD) and the true geometry of the fibers. We find an orientation error of approximately 6 degrees in voxels containing nearly parallel fibers, and 10-11 degrees in crossing fiber regions, and note that CSD was unable to resolve fibers crossing at angles below 60 degrees in our dataset. This is the first time that the 3D white matter orientation distribution is calculated from histology and compared to dMRI. Thus, this technique serves as a gold standard for dMRI validation studies - providing the ability to determine the extent to which the dMRI signal is consistent with the histological FOD, and to establish how well different dMRI models can predict the ground truth FOD. PMID- 26804783 TI - Rutin protects against aging-related metabolic dysfunction. AB - Aging is a complex process which is accompanied by multiple related chronic diseases. Among them, metabolic dysfunction is one of the most important aging related disorders. In the present study, we aimed to investigate the effect of rutin on aging-related metabolic dysfunction. We found that the increase of fasting blood glucose, insulin levels, blood pressure and HOMA-IR in aged rats was significantly inhibited by rutin. In addition, rutin improved glucose and insulin tolerance in aged rats, as reflected by decreased glucose level in IPGTT and IPITT test. Rutin treatment notably increased Akt and IRS-1 phosphorylation in the livers of old rats. The increase of inflammatory markers, such as IL-1beta and TNFalpha, was prevented by the rutin administration. Moreover, in circulation and livers of old rats, rutin treatment significantly decreased the content of TG. Rutin also inhibited the increase of serum AST and ALT levels. Furthermore, rutin treatment markedly inhibited aging-related mitochondrial dysfunction, ER stress, and oxidative stress, as evidenced by increased oxygen consumption rate and activities of Na(+)/K(+)-ATPase and Ca2(+)-ATPase, decreased expression of ATF3 and GRP78, decreased level of MDA, increased content of GSH and enhanced activity of SOD in aged rats. We show that the administration of rutin could effectively improve aging-related metabolic dysfunction. The amelioration of inflammation, lipid accumulation, mitochondrial dysfunction, ER stress, and oxidative stress may be involved in the effect of rutin on aging-related metabolic dysfunction. These findings provide novel insights into the potential use of rutin in the intervention of aging and its related metabolic diseases. PMID- 26804782 TI - In vivo observation and biophysical interpretation of time-dependent diffusion in human white matter. AB - The presence of micrometer-level restrictions leads to a decrease of diffusion coefficient with diffusion time. Here we investigate this effect in human white matter in vivo. We focus on a broad range of diffusion times, up to 600 ms, covering diffusion length scales up to about 30 MUm. We perform stimulated echo diffusion tensor imaging on 5 healthy volunteers and observe a relatively weak time-dependence in diffusion transverse to major fiber tracts. Remarkably, we also find notable time-dependence in the longitudinal direction. Comparing models of diffusion in ordered, confined and disordered media, we argue that the time dependence in both directions can arise due to structural disorder, such as axonal beads in the longitudinal direction, and the random packing geometry of fibers within a bundle in the transverse direction. These time-dependent effects extend beyond a simple picture of Gaussian compartments, and may lead to novel markers that are specific to neuronal fiber geometry at the micrometer scale. PMID- 26804784 TI - Evidence-based Frameworks for Teaching and Learning in Classical Singing Training: A Systematic Review. AB - OBJECTIVES/HYPOTHESIS: The study systematically reviews evidence-based frameworks for teaching and learning of classical singing training. STUDY DESIGN: This is a systematic review. METHODS: A systematic literature search of 15 electronic databases following the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines was conducted. Eligibility criteria included type of publication, participant characteristics, intervention, and report of outcomes. Quality rating scales were applied to support assessment of the included literature. Data analysis was conducted using meta-aggregation. RESULTS: Nine papers met the inclusion criteria. No complete evidence-based teaching and learning framework was found. Thematic content analysis showed that studies either (1) identified teaching practices in one-to-one lessons, (2) identified student learning strategies in one-to-one lessons or personal practice sessions, and (3) implemented a tool to enhance one specific area of teaching and learning in lessons. The included studies showed that research in music education is not always specific to musical genre or instrumental group, with four of the nine studies including participant teachers and students of classical voice training only. The overall methodological quality ratings were low. CONCLUSIONS: Research in classical singing training has not yet developed an evidence-based framework for classical singing training. This review has found that introductory information on teaching and learning practices has been provided, and tools have been suggested for use in the evaluation of the teaching-learning process. High quality methodological research designs are needed. PMID- 26804785 TI - Clinical Assessment of Glottal Insufficiency in Age-related Dysphonia. AB - OBJECTIVES: Incomplete glottal closure is one of the key clinical aspects of presbylarynx. The objective of the present study is to determine the diagnostic yield of several tests for the assessment of glottal competence in age-related dysphonia. STUDY DESIGN: Cross-sectional prospective. METHODS: One hundred and four healthy patients 65 years and older with a maximum phonation time below 12 seconds for women and 15 seconds for men were included. The glottal closure was assessed with laryngostroboscopy, and this observation was used as gold standard. Continuous light endoscopy, s/z ratio, electroglottography, and aerodynamic analysis of voice were performed, and their accuracy parameters for the diagnosis of the glottal gap in this context were calculated. RESULTS: A spindle-shaped gap was observed in 47 cases. Sensitivity of vocal fold bowing to predict glottal gap in phonation was 93.6% with a negative likelihood ratio of 0.15. Specificity of s/z ratio was 91.4% with a positive likelihood ratio of 6.17. Electroglottography and aerodynamic measurements of voice resulted to be inaccurate for the diagnosis of glottal insufficiency in phonation. CONCLUSIONS: Conventional endoscopy and s/z ratio are good diagnostic tests for an initial assessment of glottal insufficiency in age-related dysphonia that would allow general otolaryngologists early identification and prompt treatment of this pathology. PMID- 26804786 TI - Personal and Professional Characteristics of Music Educators: One Size Does Not Fit All. AB - OBJECTIVES/HYPOTHESIS: The prevalence of voice disorders among various educator groups is well known, and voice disorders among music educators are higher than the general classroom educators. Music educators vary with respect to behavioral and personality factors, personal characteristics, type of music taught, job specific environment, and governmental professional expectations. This study aims to identify risk factors for voice disorders in a heterogeneous population of music educators. STUDY DESIGN: An online survey was conducted with 213 respondents. METHODS: Survey questions addressed demographics, level of education, years of music teaching experience, specialty training, primary teaching assignments and instrument, vocal health behaviors, and diagnoses of voice disorders. Summary statistics and group comparisons are reported. RESULTS: Those whose primary instrument was voice reported a greater frequency of voice disorders. Female and older music educators also had a higher prevalence of voice disorders. CONCLUSIONS: Music educators are a heterogeneous group of individuals who require more careful consideration in the prevention and treatment of occupational voice problems. PMID- 26804787 TI - Andreas Vesalius' 500th Anniversary: Initial Integral Understanding of Voice Production. AB - BACKGROUND: Voice production relies on the integrated functioning of a three-part system: respiration, phonation and resonance, and articulation. To commemorate the 500th anniversary of the great anatomist Andreas Vesalius (1515-1564), we report on his understanding of this integral system. METHODS: The text of Vesalius' masterpiece De Humani Corporis Fabrica Libri Septum and an eyewitness report of the public dissection of three corpses by Vesalius in Bologna, Italy, in 1540, were searched for references to the voice-producing anatomical structures and their function. We clustered the traced, separate parts for the first time. RESULTS: We found that Vesalius recognized the importance for voice production of many details of the respiratory system, the voice box, and various structures of resonance and articulation. He stressed that voice production was a cerebral function and extensively recorded the innervation of the voice-producing organs by the cranial nerves. CONCLUSIONS: Vesalius was the first to publicly record the concept of voice production as an integrated and cerebrally directed function of respiration, phonation and resonance, and articulation. In doing so nearly 500 years ago, he laid a firm basis for the understanding of the physiology of voice production and speech and its management as we know it today. PMID- 26804789 TI - Enhanced photoelectric properties by the coordinating role of doping and modification. AB - Dual technique design in this research has successfully enriched the complementation between doping and surface modification. Here, Co(2+) doped Ag ZnO nanocomposites (CAZ NCs) are mass produced by the combustion method. The HRTEM image shows that the doped Co(2+) and the surface modified Ag nanoparticles on the ZnO NCs are influential on the preferential orientation. Based on the conductivity formula sigma = nqMU and the actual verification, the improved photoelectric properties of CAZ NCs under visible light irradiation are attributed to the enhanced light absorption and the weakened recombination of photogenerated electron-hole pairs. It would be instructive for the sound design concept of subsequent material development. PMID- 26804788 TI - Vocal Control: Is It Susceptible to the Negative Effects of Self-Regulatory Depletion? AB - OBJECTIVES: Self-regulation (SR) relies on the capacity to modify behavior. This capacity may diminish with use and result in self-regulatory depletion (SRD), or the reduced ability to engage in future SR efforts. If the SRD effect applies to vocal behavior, it may hinder success during behavioral voice treatment. Thus, this proof-of-concept study sought to determine whether SRD affects vocal behavior change and if so, whether it can be repaired by an intervention meant to replete SR resources. METHODS: One hundred four women without voice disorders were randomized into groups that performed either (1) a high-SR writing task followed by a high-SR voice task; (2) a low-SR writing task followed by a high-SR voice task; or (3) a high-SR writing task followed by a relaxation intervention and a high-SR voice task. The high-SR voice tasks in all groups involved suppression of the Lombard effect during reading and free speech. RESULTS: The low-SR group suppressed the Lombard effect to a greater extent than the high-SR group and high-SR-plus-relaxation group on the free speech task. There were no significant group differences on the reading task. CONCLUSIONS: Findings suggest that SRD may present challenges to vocal behavior modification during free speech but not reading. Furthermore, relaxation did not significantly replete self regulatory resources for vocal modification during free speech. Findings may highlight potential considerations for voice treatment and assessment and support the need for future research focusing on effective methods to test self regulatory capacity and replete self-regulatory resources in voice patients. PMID- 26804790 TI - Confinement-deconfinement transition due to spontaneous symmetry breaking in quantum Hall bilayers. AB - Band-inverted electron-hole bilayers support quantum spin Hall insulator and exciton condensate phases. Interest in quantum spin Hall effect in these systems has recently put them in the spotlight. We investigate such a bilayer in an external magnetic field. We show that the interlayer correlations lead to formation of a helical quantum Hall exciton condensate state. Existence of the counterpropagating edge modes in this system results in formation of a ground state spin-texture not supporting gapless single-particle excitations. The charged edge excitations in a sufficiently narrow Hall bar are confined: a charge on one of the edges always gives rise to an opposite charge on the other edge. Magnetic field and gate voltages allow the control of a confinement-deconfinement transition of charged edge excitations, which can be probed with nonlocal conductance. Confinement-deconfinement transitions are of great interest, not least because of their possible significance in shedding light on the confinement problem of quarks. PMID- 26804791 TI - Development of Personalized Health Messages to Promote Engagement in Advance Care Planning. AB - OBJECTIVES: To develop and test the acceptability of personalized intervention materials to promote advance care planning (ACP) based on the Transtheoretical Model (TTM), in which readiness to change is a critical organizing construct. DESIGN: Development study creating an expert system delivering TTM-personalized feedback reports and stage-matched brochures with more-general information on ACP and modifications based on participant reviews. SETTING: Senior centers. PARTICIPANTS: Community-living persons aged 65 and older (N = 77). MEASUREMENTS: Participant ratings of length, attractiveness, and trustworthiness of and reactions to reports and brochures. RESULTS: The expert system assessed participants' readiness to engage in each of four ACP behaviors: completion of a living will, naming a health care proxy, communication with loved ones about quality vs quantity of life, and communication with clinicians about quality vs quantity of life. The system also assessed pros and cons of engagement and values and beliefs that influence engagement. The system provided individualized feedback based on the assessment, with brochures providing additional general information. Initial participant review indicating unacceptable length led to revision of feedback reports from full-sentence paragraph format to bulleted format. After review, the majority of participants rated the materials as easy to read, trustworthy, providing new information, making them more comfortable reading about ACP, and increasing interest in participating in ACP. CONCLUSION: Older adults found an expert system individualized feedback report and accompanying brochure to promote ACP engagement to highly acceptable and engaging. Additional research is necessary to examine the effects of these materials on behavior change. PMID- 26804792 TI - Galactomannan enzyme immunoassay and quantitative Real Time PCR as tools to evaluate the exposure and response in a rat model of aspergillosis after posaconazole prophylaxis. AB - INTRODUCTION: A steroid-immunosuppressed rat model of invasive pulmonary aspergillosis was use to examine the usefulness of galactomannan enzyme immunoassay (GM) and quantitative real time PCR (RT-PCR) in evaluating the association between response and exposure after a high dose of prophylactic posaconazole. METHODS: Two different strains of Aspergillus fumigatus with different in vitro posaconazole susceptibility were used. RESULTS: Serum concentrations demonstrated similar posaconazole exposure for all treated animals. However, response to posaconazole relied on the in vitro susceptibility of the infecting strain. After prophylaxis, galactomannan index and fungal burden only decreased in those animals infected with the most susceptible strain. CONCLUSION: This study demonstrated that both biomarkers may be useful tools for predicting efficacy of antifungal compounds in prophylaxis. PMID- 26804793 TI - Experiential self-understanding. AB - The notion of insight is at one and the same time central to psychoanalysis and to the self-understanding that is part of everyday life. Through clinical material and critical engagement with contemporary philosophical work on self knowledge, this paper clarifies one crucial aspect of this key notion. Self understanding of the sort we have in mind, while of course involving cognitive elements, is not sufficiently accounted for by cognition about one's affects, motivations, or other aspects of the psyche, nor by the simple conjunction of such cognition with felt affect, motivational urges, etc. Nor is it best modelled in terms of internal self-observation. Rather, it is the product of an ongoing process of the unfolding articulation of one's psychic life. The notion of experience is important here in three ways. First, lived experience is that out of which the self-understanding arises. Second, this self-understanding is a development and articulation of these aspects of our inner lives; it is a part of that same lived perspective. And third, this understanding in turn shapes one's experience of one's inner world: as it is attained, one's experience of oneself thereby changes. Central here is the emphasis upon a developing process involving the ability to speak from one's subjective perspective while experiencing one's subjective perspective as the perspective that it is. PMID- 26804794 TI - Evaluation of Stress-Induced Microbial Siderophore from Pseudomonas aeruginosa Strain S1 as a Potential Matrix Metalloproteinase Inhibitor in Wound Healing Applications. AB - Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes capable of causing various inflammatory and various degenerative diseases if over expressed. The active site of these enzymes is a zinc binding motif which binds to the specific site on the substrate and induce degradation. Hence an inhibitor is required to form a complex with zinc motif which hampers the binding ability of MMPs. To obtain novel MMPs inhibitor for wound healing, the chelating activity of siderophore from the microbial source was focused. During screening for siderophore production, strain S1 produced the highest amount of siderophore in the minimal salts medium. The isolate was confirmed as Pseudomonas aeruginosa strain S1 based on 16S rRNA gene sequencing and phylogenetic analysis. The activity of the siderophore was assayed using chrome azurol sulphonate and purified by the chromatographic techniques. The structural evidence through Fourier transform infrared and nuclear magnetic resonance spectra revealed that the isolated siderophore is a catecholate type with the distinctive characters. The positive results of calcein and fluozin-3 assays indicate that siderophore could bind to divalent metal ions, namely Fe(2+) and Zn(2+). As the siderophore compound focused on wound healing property, the in vitro studies revealed the viability of NH3T3 fibroblast cells and its efficiency in matrix modulating was confirmed through gelatin zymogram. PMID- 26804796 TI - MOTIVATIONAL TYPES AMONG COLLEGE STUDENTS. AB - College students were related to one another over a variety of measures associated with motivation to study in college. The inverse factor analysis of these relahionships revealed ten motivational types. Data for 12 hypothetical students, entering the analysis as an extension matrix, helped to interpret the types found among the real studenb. In a table of results, the average value on each measure for students of each type k compared with the average value for students who were found to be the opposites of each type. Consistencies among the measures of each type make good psychological sense. In addition, the actual studenb, all known personally to the author, seemed adequately to belong to the types into which the analysis placed them. PMID- 26804797 TI - SOCIAL DESIRABILITY AND THE TSC MMPI SCALES. AB - The seven Minnesota Multiphasic Personality Inventory (MMPI) scales developed by Tryon, Stein, and Chu were intercorrelated and factor analyzed by the method of principal components. Included in the analysis were three marker scales for the first three principal components of the MMPI: the SD scale, the R scale, and the L scale, respectively. All of the TSC scales had loadings of .61 OT higher on the first principal component marked by the SD scale with a loading of -.90. The results show that there is con- siderable redundancy in the seven TSC scales and that each of lthe scales has its largest loading on the first principal component. PMID- 26804798 TI - THE TSC SCALES : SOCIAL UNDESIRABILITY OR PERSONAL MALADJUSTMENT? A REPLY TO EDWARDS, KLOCKARS, AND ABBOTT. PMID- 26804795 TI - Application of Routine Diagnostic Procedure, VITEK 2 Compact, MALDI-TOF MS, and PCR Assays in Identification Procedure of Bacterial Strain with Ambiguous Phenotype. AB - In diagnostic microbiology as well as in microbiological research, the identification of a microorganism is a crucial and decisive stage. A broad choice of methods is available, based on both phenotypic and molecular properties of microbes. The aim of this study was to compare the application of phenotypic and molecular tools in bacterial identification on the example of Gram-negative intestine rod with an ambiguous phenotype. Different methods of identification procedure, which based on various properties of bacteria, were applied, e.g., microscopic observation of single-bacterial cells, macroscopic observation of bacterial colonies morphology, the automated system of microorganism identification (biochemical tests), the mass spectrometry method (analysis of bacterial proteome), and genetic analysis with PCR reactions. The obtained results revealed discrepancies in the identification of the tested bacterial strain with an atypical phenotype: mucous morphology of colonies, not characteristic for either E. coli and Citrobacter spp., mass spectrometry analysis of proteome initially assigned the tested strain to Citrobacter genus (C. freundii) and biochemical profiles pointed to Escherichia coli. A decisive method in the current study was genetic analysis with PCR reactions which identified conserved genetic sequences highly specific to E. coli species in the genome of the tested strain. PMID- 26804799 TI - A STUDY OF THE RELIABILITY OF BY ITERATIVE, INTERCOLUMNAR CORRELATIONAL ANALYSIS INTRA-INDIVIDUAL PERSONALITY STRUCTURE. AB - This paper illustrakes Iterative, Intercolumnar Correlational Analysis, both single and multiple methods (McQuitty, 1967, 1968; McQuitty and Clark, 1968). It is applied to a test designed to assess psychological well-being. The test is derived from the same general theory as the method of analysis. The method is applied in the paktern analysis of both composite matrices of interassociation land matrices genemted from results by the single individual. The test and method investigate intra-individual personality structure as well as composite personality structure. PMID- 26804800 TI - A COMBINED FACTOR ANALYSIS OF CREATIVITY AND INTELLIGENCE. AB - A battery of tests was given to 447 studenits in the secondary schools of Alcoa, Tennessee. The tests were composed of the Lorge-Thorndike Intelligence Tests, and five selected creativity tests. The combined battery of tests was factor analyzed and rotated to an oblique simple structure, and then to a hierachical solution. Three factors were found: the verbal intelligence and reasoning factors identified in many previous studies, and a creativity faotor. The structure was very oblique. The second order factor, g, was found to count for 77% of the variance of the verbal facbor, 89% of the reasoning factor and 48% of the creativity factor. These results were compared with those of previous studies of creativity and intelligence. PMID- 26804801 TI - THE INFLUENCE OF AGE AND SOCIAL CLASS ON AUTHORITARIAN FAMILY IDEOLOGY. AB - The Authoritarian Family Ideology Scale (AFI,,) was administered to four hundred and thirty eight mothers towards the end of their confinement. Raw scores were analyzed by means of multiple linear regression. Chrono- logical age and social class scores were found to give substantial accounts of criterion variance. AFI,, scores tended to drop as age and social class rose. Interaction and curvilinearity did not increase R2 values to a substantial degree. PMID- 26804802 TI - FACTORS OF EMOTIONALITY RELATED TO ALCOHOL CONSUMPTION IN LABORATORY MICE. AB - Fifty mice from four genotypes were tested on a factor analyzed battery of measures of emotionality. This was followed by testing of alcohol consumption. The factors were related to alcohol consumption by a stepwise regression procedure. Among the five best predictors, Factor B, interpreted as a disorganization factor and Factor C, interpreted as an audiogenic reactivity factor, were most consistently related to alcohol consumption. PMID- 26804803 TI - EVALUATING THE IMPORTANCE OF FACTORS IN ANY GIVEN ORDER OF FACTORING. AB - A methodology has been described and illustrated for obtaining an evaluation of the importance of the factors in a particular order of factoring that does not require faotoring beyond that order. For example, one can estimate the intercorrelations of the original measures with the perturbations of the first order factor held constant or, the reverse, estimate the contribution to the intercorrelations of the originral measures from the first-order factors alone. Similar operations are possible at higher orders. PMID- 26804804 TI - A PARTITIONING OF ORDINAL INFORMATION IN A THREE-WAY CROSS-CLASSIFICATION. AB - In summarizing ordinal data with many tied rankings, generally pre- sented in the form of a cross-tabulation, there are many considerations that enter into the selection of a statistic summarizing the degree of association. When more than two variables are analyzed simultaneously the situation is even more complex. This paper considers, for the joint distribution of three ordinal variables, the interpretation of a set of summary statistics having product-moment characteristics. This interpretation sheds some light on general problems of analysis of causal relations and relates these summary statistics to other procedures for analyzing attribute data. They are illustrated by re-analyzing some data used by Siege1 to illustrate a similar procedure. PMID- 26804805 TI - ON THE GENERALIZATION OF THE BURT RECIPROCITY PRINCIPLE. AB - A method for linking Q and R factors of a single score matrix is described. The method is applicable for dichotomous entries in the score matrix, and uses the G Index as a mediating index of association. The final linkage is based upon correlation coefficients. Two alternative methods for obtaining the same results are described; and relationships between all three methods are ex- plained. The application of the procedures is limited to the case of orthogonal factor solutions. PMID- 26804807 TI - Reported provision of analgesia to patients with acute abdominal pain in Canadian paediatric emergency departments. AB - OBJECTIVES: Evidence exists that analgesics are underutilized, delayed, and insufficiently dosed for emergency department (ED) patients with acute abdominal pain. For physicians practicing in a Canadian paediatric ED setting, we (1) explored theoretical practice variation in the provision of analgesia to children with acute abdominal pain; (2) identified reasons for withholding analgesia; and (3) evaluated the relationship between providing analgesia and surgical consultation. METHODS: Physician members of Paediatric Emergency Research Canada (PERC) were prospectively surveyed and presented with three scenarios of undifferentiated acute abdominal pain to assess management. A modified Dillman's Tailored Design method was used to distribute the survey from June to July 2014. RESULTS: Overall response rate was 74.5% (149/200); 51.7% of respondents were female and mean age was 44 (SD 8.4) years. The reported rates of providing analgesia for case scenarios representative of renal colic, appendicitis, and intussusception, were 100%, 92.1%, and 83.4%, respectively, while rates of providing intravenous opioids were 85.2%, 58.6%, and 12.4%, respectively. In all 60 responses where the respondent indicated they would obtain a surgical consultation, analgesia would be provided. In the 35 responses where analgesia would be withheld, 21 (60%) believed pain was not severe enough, while 5 (14.3%) indicated it would obscure a surgical condition. CONCLUSIONS: Pediatric emergency physicians self-reported rates of providing analgesia for acute abdominal pain scenarios were higher than previously reported, and appeared unrelated to request for surgical consultation. However, an unwillingness to provide opioid analgesia, belief that analgesia can obscure a surgical condition, and failure to take self reported pain at face value remain, suggesting that the need exists for further knowledge translation efforts. PMID- 26804809 TI - Direct effect of infliximab on intestinal mucosa sustains mucosal healing: exploring new mechanisms of action. AB - BACKGROUND: Infliximab is effective in inflammatory bowel disease through several mechanisms, possibly acting at the mucosal level. AIM: To assess the role of infliximab on intestinal mucosa and whether it contributes to mucosal healing. METHODS: Human colonic mucosal biopsies were incubated with or without infliximab. Cultured biopsies were evaluated for histological staining, CD68, CD3, E-cadherin and phospho-extracellular signal-regulated kinases (ERK) expression, and apoptosis. A scratch assay and MTT assay were performed with Caco2 cells in the presence of infliximab and/or tumour necrosis factor (TNF) alpha or treated with supernatants obtained from human peripheral blood mononuclear cells or human intestinal fibroblasts treated with TNF-alpha and infliximab alone or in association. RESULTS: Infliximab-treated biopsies displayed a better histological appearance, reduced inflammation with an increase of E-cadherin, phospho-ERK and apoptosis. Supernatants showed lower TNF-alpha, IL 17, IL-6 and IL-8 concentration, with an increase in fibroblast-growth-factor. Motility at scratch assay and proliferation at MTT assay of Caco2 cells displayed differential modulation by TNF-alpha and infliximab, directly or through supernatants of human intestinal fibroblasts and human peripheral blood mononuclear cells exposed to them. CONCLUSION: Infliximab contributes to the mucosal healing process by acting directly at an intestinal mucosal level; infliximab indirectly affects epithelial cell migration and proliferation by acting on both fibroblasts and leukocytes. PMID- 26804811 TI - Effects of glutathione on sperm quality during liquid storage in boars. AB - The aim of this study was to investigate the effects of different concentrations of glutathione in Modena on boar sperm quality during liquid storage at 17 degrees C. Boar semen samples were collected and diluted with Modena containing different concentrations (0, 1, 5, 10, 15 mmol/L) of glutathione. Sperm motility, effective survival period, plasma membrane integrity, acrosome integrity, total antioxidant capacity (T-AOC) activity, malondialdehyde (MDA) content and hydrogen peroxide (H2 O2 ) content were measured and analyzed. The results showed that Modena supplemented with 1, 5 and 10 mmol/L glutathione improved sperm motility, effective survival period, plasma membrane integrity and T-AOC, and decreased MDA content and H2 O2 content. Meanwhile, the semen sample diluted with Modena containing 1 mmol/L glutathione achieved optimum effect, and effective survival period was 6.1 days. After 5 days preservation, sperm motility, plasma membrane integrity and T-AOC of the group treated with 1 mmol/L glutathione were all higher than that of other groups. Meanwhile, MDA content and H2 O2 content were lower than that of other groups. In conclusion, Modena supplemented with glutathione decreased the oxidative stress and improved the quality of boar semen during liquid storage at 17 degrees C, and 1 mmol/L concentration was the optimum concentration. (c) 2016 Japanese Society of Animal Science. PMID- 26804812 TI - Structured training and competence assessment in colorectal robotic surgery. Results of a consensus experts round table. AB - BACKGROUND: A structured training is a key element for the learning of techniques with a high level of complexity, such as robotic colorectal surgery. METHODS: This study reports the results of an expert consensus round table held during the 6th Clinical Robotic Surgery Association (CRSA) congress, focusing on recommendations in robotic colorectal surgery. RESULTS: Three sequential steps are proposed for training: a basic module, to learn basic robotic skills and general competencies; an advanced module, to acquire skills to safely perform a colorectal resection, and tutored clinical practice providing procedures of increasing complexity. Each specific skill of the basic module and performance of each surgical step of a colorectal procedure was evaluated and rated from 1 to 3. CONCLUSIONS: Defining requirements to begin robotic colorectal activity, delineation of structured training programs and objectification of the acquired competences are key elements for a safe and efficient learning of robotic colorectal surgery. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26804813 TI - Core Binding Factor beta of Osteoblasts Maintains Cortical Bone Mass via Stabilization of Runx2 in Mice. PMID- 26804816 TI - Geographical isolation caused the diversification of the Mediterranean thorny cushion-like Astragalus L. sect. Tragacantha DC. (Fabaceae). AB - Understanding the origin and evolution of Mediterranean vascular flora within the long-term context of climate change requires a continuous study of historical biogeography supported by molecular phylogenetic approaches. Here we provide new insights into the fascinating but often overlooked diversification of Mediterranean xerophytic plants. Growing in some of the most stressing Mediterranean environments, i.e. coastal and mountainous opened habitats, the circum-Mediterranean Astragalus L. sect. Tragacantha DC. (Fabaceae) gathers several thorny cushion-like taxa. These have been the subjects of recent taxonomical studies, but they have not yet been investigated within a comprehensive molecular framework. Bayesian phylogenetics applied to rDNA ITS sequences reveal that the diversification of A. sect. Tragacantha has roots dating back to the Pliocene, and the same data also indicate an eastern-western split giving rise to the five main lineages that exist today. In addition, AFLP fingerprinting supports an old east-west pattern of vicariance that completely rules out the possibility of a recent eastern origin for western taxa. The observed network of genetic relationships implies that contrary to what is widely claimed in the taxonomic literature, it is range fragmentation, as opposed to a coastal-to-mountain ecological shift, that is likely the main driver of diversification. PMID- 26804817 TI - Phylogenetic affinities of the Fregetta storm-petrels are not black and white. AB - The Fregetta storm-petrels generally are regarded to comprise two species: black bellied storm-petrels F. tropica (monotypic) breed at Antarctic and sub-Antarctic islands (46-63 degrees S), and white-bellied storm-petrels F. grallaria breed at south temperate islands (28-37 degrees S), with four recognized subspecies. Confusion surrounds the status of birds at Gough Island (40 degrees S), central South Atlantic, which have been attributed usually to a white-bellied form of black-bellied storm-petrel F. t. melanoleuca. We use cytochrome b and nuclear beta-fibrinogen gene sequences to show that F. t. melanoleuca are present during the breeding season at Gough and islands in the nearby Tristan da Cunha archipelago (37 degrees S), exhibiting limited divergence from F. t. tropica. We also show that there is greater diversity among F. grallaria populations, with eastern South Pacific F. g. segethi and F. g. titan differing by c. 0.011, and both differing from western South Pacific nominate F. g. grallaria by c. 0.059. The Tristan archipelago supports a population of F. grallaria closely allied to the nominate form, as well as a distinct form identified as F. g. leucogaster. Further research is needed to assess how F. grallaria and F. tropica segregate in sympatry at Tristan and Gough, and why this is the only location where both species have white-bellies. PMID- 26804818 TI - [Pseudopheochromocytoma caused by clozapine]. PMID- 26804815 TI - Extrinsic and Intrinsic Mechanisms by Which Mesenchymal Stem Cells Suppress the Immune System. AB - Mesenchymal stem cells (MSCs) are a group of fibroblast-like multipotent mesenchymal stromal cells that have the ability to differentiate into osteoblasts, adipocytes, and chondrocytes. Recent studies have demonstrated that MSCs possess a unique ability to exert suppressive and regulatory effects on both adaptive and innate immunity in an autologous and allogeneic manner. A vital step in stem cell transplantation is overcoming the potential graft-versus-host disease, which is a limiting factor to transplantation success. Given that MSCs attain powerful differentiation capabilities and also present immunosuppressive properties, which enable them to survive host immune rejection, MSCs are of great interest. Due to their ability to differentiate into different cell types and to suppress and modulate the immune system, MSCs are being developed for treating a plethora of diseases, including immune disorders. Moreover, in recent years, MSCs have been genetically engineered to treat and sometimes even cure some diseases, and the use of MSCs for cell therapy presents new perspectives for overcoming tissue rejection. In this review, we discuss the potential extrinsic and intrinsic mechanisms that underlie MSCs' unique ability to modulate inflammation, and both innate and adaptive immunity. PMID- 26804819 TI - [Tonic pupil as an initial manifestation of Sjogren's syndrome]. PMID- 26804820 TI - Antibody blockade of mucosal addressin cell adhesion molecule-1 attenuates proinflammatory activity of mesenteric lymph after hemorrhagic shock and resuscitation. AB - BACKGROUND: The current study was designed to determine the effects of antibody blockade of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) on the proinflammatory activity of mesenteric lymph after hemorrhagic shock and resuscitation (HS/R). METHODS: Rats were subjected to HS/R with or without treatment with MAdCAM-1 polyclonal antibody. MAdCAM-1 expression and lymphocyte infiltration in rats were examined. Post-shock mesenteric lymph was collected, filtered to remove lymphocytes, and transfused into recipient mice to induce systemic inflammation and intestinal injury. The proinflammatory activity of post shock lymph in mice was determined by examining intestinal permeability, enterocyte apoptosis, intestinal lactate levels, lung myeloperoxidase (MPO) activity, and serum cytokine levels. Survival of recipient mice was determined over a 1-week time period. RESULTS: Rats subjected to HS/R had increased MAdCAM-1 expression and lymphocyte infiltration in the intestine. Antibody blockade of MAdCAM-1 attenuated the increased lymphocyte infiltration after HS/R (P < .05). Post-shock mesenteric lymph transfusion significantly increased mortality accompanied by increases in gut permeability, enterocyte apoptosis, intestinal lactate levels, lung MPO activity, and serum levels of interleukin (IL)-1beta, IL 6, tumor necrosis factor (TNF)-alpha, IL-10, and transforming growth factor-beta (all P < .05). Antibody blockade of MAdCAM-1 in rats subjected to HS/R attenuated the proinflammatory activity of post-shock mesenteric lymph, with abrogation of lymph transfusion-induced increases in mortality, gut permeability, epithelial cell apoptosis, intestinal lactate levels, lung MPO activity, and serum levels of IL-1beta, IL-6, and TNF-alpha (all P < .05). CONCLUSION: These findings demonstrate that antibody blockade of MAdCAM-1 attenuates the proinflammatory activity of mesenteric lymph after HS/R. PMID- 26804821 TI - The effect of early mobilization protocols on postoperative outcomes following abdominal and thoracic surgery: A systematic review. AB - BACKGROUND: Early mobilization is considered an important element of postoperative care; however, how best to implement this intervention in clinical practice is unknown. This systematic review summarizes the evidence regarding the impact of specific early mobilization protocols on postoperative outcomes after abdominal and thoracic surgery. METHOD: The review was performed according to PRISMA guidelines. We searched 8 electronic databases to identify studies comparing patients receiving a specific protocol of early mobilization to a control group. Methodologic quality was assessed using the Downs and Black tool. RESULTS: Four studies in abdominal surgery (3 randomized controlled trials [RCTs] and 1 observational prospective study) and 4 studies in thoracic surgery (3 RCTs and 1 observational retrospective study) were identified. None of the 5 studies evaluating postoperative complications reported differences between groups. One of 4 studies evaluating duration of stay reported a significant decrease in the intervention group. One of 3 studies evaluating gastrointestinal function reported differences in favor of the intervention group. One of 4 studies evaluating performance-based outcomes reported differences in favor of the intervention group. One of 5 studies evaluating patient-reported outcomes reported differences in favor of the intervention group. Overall methodologic quality was poor. CONCLUSION: Few comparative studies have evaluated the impact of early mobilization protocols on outcomes after abdominal and thoracic surgery. The quality of these studies was poor and results were conflicting. Although bed rest is harmful, there is little available evidence to guide clinicians in effective early mobilization protocols that increase mobilization and improve outcomes. PMID- 26804822 TI - Ultrasound-guided radiofrequency-assisted segmental liver resection. PMID- 26804823 TI - Medical telementoring using an augmented reality transparent display. AB - BACKGROUND: The goal of this study was to design and implement a novel surgical telementoring system called the System for Telementoring with Augmented Reality (STAR) that uses a virtual transparent display to convey precise locations in the operating field to a trainee surgeon. This system was compared with a conventional system based on a telestrator for surgical instruction. METHODS: A telementoring system was developed and evaluated in a study which used a 1 * 2 between-subjects design with telementoring system, that is, STAR or conventional, as the independent variable. The participants in the study were 20 premedical or medical students who had no prior experience with telementoring. Each participant completed a task of port placement and a task of abdominal incision under telementoring using either the STAR or the conventional system. The metrics used to test performance when using the system were placement error, number of focus shifts, and time to task completion. RESULTS: When compared with the conventional system, participants using STAR completed the 2 tasks with less placement error (45% and 68%) and with fewer focus shifts (86% and 44%), but more slowly (19% for each task). CONCLUSIONS: Using STAR resulted in decreased annotation placement error, fewer focus shifts, but greater times to task completion. STAR placed virtual annotations directly onto the trainee surgeon's field of view of the operating field by conveying location with great accuracy; this technology helped to avoid shifts in focus, decreased depth perception, and enabled fine-tuning execution of the task to match telementored instruction, but led to greater times to task completion. PMID- 26804824 TI - Insight into the electronic effect of phosphine ligand on Rh catalyzed CO2 hydrogenation by investigating the reaction mechanism. AB - Improving the catalytic efficiency of CO2 hydrogenation is a big challenge in catalysed CO2 recycling and H2 conservation. The detailed mechanism of [Rh(PCH2X(R)CH2P)2](+) (X(R) = CH2, N-CH3, CF2) catalyzed CO2 hydrogenation is studied to obtain insights into the electronic effect of the substituents at diphosphine ligand on the catalytic efficiency. The most favorable reaction mechanism is found to be composed of three steps: (1) oxidative addition of dihydrogen onto the Rh center of the catalyst; (2) the first hydride abstraction by base from the Rh dihydride complexes; (3) the second hydride transfer from the Rh hydride complexes to CO2. It was found that the transition state for the first hydride abstraction from the Rh dihydride complex is the TOF-determining transition state (TDTS) in the most favorable mechanism. The energetic span (deltaE) of the cycle is suggested related to the thermodynamic hydricity of the Rh dihydride complex. Model catalyst [Rh(PCH2CF2CH2P)2](+) with a strong sigma electron withdrawing group on the diphosphine ligand provides higher hydricity in the Rh dihydride complex and lower activation energy when compared with the other two catalysts. Our study shows that it is the sigma electron withdrawing ability rather than the electron donating ability that enhances the catalytic efficiency in catalyzed CO2 hydrogenation. This finding will benefit ligand design in transition metal catalysts and lead to more efficient methods for CO2 transformation. PMID- 26804825 TI - Orbital Delocalization and Enhancement of Magnetic Interactions in Perovskite Oxyhydrides. AB - Recent experiments showed that some perovskite oxyhydrides have surprisingly high magnetic-transition temperature. In order to unveil the origin of this interesting phenomenon, we investigate the magnetism in SrCrO2H and SrVO2H on the basis of first-principles calculations and Monte Carlo simulations. Our work indicates that the Cr-O-Cr superexchange interaction in SrCrO2H is unexpectedly strong. Different from the previous explanation in terms of the H(-) ion substitution induced increase of the Cr-O-Cr bond angle, we reveal instead that this is mainly because the 3d orbitals in perovskite oxyhydrides becomes more delocalized since H(-) ions have weaker electronegativity and less electrons than O(2-) ions. The delocalized 3d orbitals result in stronger Cr-O interactions and enhance the magnetic-transition temperature. This novel mechanism is also applicable to the case of SrVO2H. Furthermore, we predict that SrFeO2H will have unprecedented high Neel temperature because of the extraordinarily strong Fe-H-Fe sigma-type interactions. Our work suggests the anion substitution can be used to effectively manipulate the magnetic properties of perovskite compounds. PMID- 26804826 TI - Sexual Conspecific Aggressive Response (SCAR): A Model of Sexual Trauma that Disrupts Maternal Learning and Plasticity in the Female Brain. AB - Sexual aggression can disrupt processes related to learning as females emerge from puberty into young adulthood. To model these experiences in laboratory studies, we developed SCAR, which stands for Sexual Conspecific Aggressive Response. During puberty, a rodent female is paired daily for 30-min with a sexually-experienced adult male. During the SCAR experience, the male tracks the anogenital region of the female as she escapes from pins. Concentrations of the stress hormone corticosterone were significantly elevated during and after the experience. Moreover, females that were exposed to the adult male throughout puberty did not perform well during training with an associative learning task nor did they learn well to express maternal behaviors during maternal sensitization. Most females that were exposed to the adult male did not learn to care for offspring over the course of 17 days. Finally, females that did not express maternal behaviors retained fewer newly-generated cells in their hippocampus whereas those that did express maternal behaviors retained more cells, most of which would differentiate into neurons within weeks. Together these data support SCAR as a useful laboratory model for studying the potential consequences of sexual aggression and trauma for the female brain during puberty and young adulthood. PMID- 26804896 TI - Harnessing Protocolized Adaptation in Dissemination: Successful Implementation and Sustainment of the Veterans Affairs Coordinated-Transitional Care Program in a Non-Veterans Affairs Hospital. AB - The Department of Veterans Affairs (VA) Coordinated-Transitional Care (C-TraC) program is a low-cost transitional care program that uses hospital-based nurse case managers, inpatient team integration, and in-depth posthospital telephone contacts to support high-risk patients and their caregivers as they transition from hospital to community. The low-cost, primarily telephone-based C-TraC program reduced 30-day rehospitalizations by one-third, leading to significant cost savings at one VA hospital. Non-VA hospitals have expressed interest in launching C-TraC, but non-VA hospitals differ in important ways from VA hospitals, particularly in terms of context, culture, and resources. The objective of this project was to adapt C-TraC to the specific context of one non VA setting using a modified Replicating Effective Programs (REP) implementation theory model and to test the feasibility of this protocolized implementation approach. The modified REP model uses a mentored phased-based implementation with intensive preimplementation activities and harnesses key local stakeholders to adapt processes and goals to local context. Using this protocolized implementation approach, an adapted C-TraC protocol was created and launched at the non-VA hospital in July 2013. In its first 16 months, C-TraC successfully enrolled 1,247 individuals with 3.2 full-time nurse case managers, achieving good fidelity for core protocol steps. C-TraC participants experienced a 30-day rehospitalization rate of 10.8%, compared with 16.6% for a contemporary comparison group of similar individuals for whom C-TraC was not available (n = 1,307) (P < .001). The new C-TraC program continues in operation. Use of a modified REP model to guide protocolized adaptation to local context resulted in a C-TraC program that was feasible and sustained in a real-world non-VA setting. A modified REP implementation framework may be an appropriate foundational step for other clinical programs seeking to harness protocolized adaptation in mentored dissemination activities. PMID- 26804897 TI - Experimental evidence for drought induced alternative stable states of soil moisture. AB - Ecosystems may exhibit alternative stable states (ASS) in response to environmental change. Modelling and observational data broadly support the theory of ASS, however evidence from manipulation experiments supporting this theory is limited. Here, we provide long-term manipulation and observation data supporting the existence of drought induced alternative stable soil moisture states (irreversible soil wetting) in upland Atlantic heath, dominated by Calluna vulgaris (L.) Hull. Manipulated repeated moderate summer drought, and intense natural summer drought both lowered resilience resulting in shifts in soil moisture dynamics. The repeated moderate summer drought decreased winter soil moisture retention by ~10%. However, intense summer drought, superimposed on the experiment, that began in 2003 and peaked in 2005 caused an unexpected erosion of resilience and a shift to an ASS; both for the experimental drought manipulation and control plots, impairing the soil from rewetting in winter. Measurements outside plots, with vegetation removal, showed no evidence of moisture shifts. Further independent evidence supports our findings from historical soil moisture monitoring at a long-term upland hydrological observatory. The results herald the need for a new paradigm regarding our understanding of soil structure, hydraulics and climate interaction. PMID- 26804898 TI - Characteristics of veterans receiving buprenorphine vs. methadone for opioid use disorder nationally in the Veterans Health Administration. AB - BACKGROUND: The advent of buprenorphine as an alternative to methadone has dramatically shifted the landscape of opioid agonist therapy (OAT) for opioid use disorder (OUD). However, there is limited US national level data describing thedifferences between patients who are prescribed these two OAT options. METHODS: From veterans with OUD diagnosis who used Veterans Health Administration services in 2012, we identified 3 mutually exclusive groups: those who received (1) buprenorphine only (n=5,670); (2) methadone only (n=6,252); or (3) both buprenorphine and methadone in the same year (n=2513). We calculated the bi varate effect size differences (risk ratios and Cohen's d) forcharacteristics that differentiated these groups. Logistic regression analysis was then used to identify factors independently differentiating the groups. RESULTS: Ten year increment in age (OR 0.67; 95% CI 0.64-0.70), urban residence (OR 0.26; 95% CI 0.25-0.33), and black race (OR 0.39; 95% CI 0.35-0.43) were strongly and negatively associated with odds of receiving buprenorphine compared to methadone, while medical and psychiatric comorbidities or receipt of other psychiatric medications did not demonstrate substantial differences between groups. CONCLUSIONS: Differences between veterans receiving buprenorphine or methadone based OAT seems to be largely shaped by demographic characteristics rather than medical or psychiatric or service use characteristics. A clearer understanding of the reasons for racial differences could be helpful in assuring that black OUD patients are not denied the opportunity to receive buprenorphine if that is their preference. PMID- 26804899 TI - A longitudinal study of cotinine in long-term daily users of e-cigarettes. AB - BACKGROUND: It is not clear whether, in established vapers, cotinine levels remain stable or change over time. METHODS: We enrolled 98 exclusive users of e cigarettes on websites and forums dedicated to smoking cessation and to e cigarettes. We collected saliva vials by mail in 2013-2014 (baseline), and collected a second saliva vial eight months later (follow-up) in the same participants. Participants had not used any tobacco or nicotine medications in the previous five days. Cotinine in saliva was analyzed with liquid chromatography-mass spectrometry. Use of e-cigarettes, tobacco and nicotine medications was self-reported. RESULTS: All participants were former smokers, and 99% were using e-cigarettes daily. They had already been using e-cigarettes for nine months on average at baseline. The median cotinine level was 252ng/mL at baseline (quartiles: 124-421ng/mL) and 307ng/mL at follow-up (114-466ng/mL, W=0.9, p=0.4 for change over time). The median concentration of nicotine in refill liquids was 11mg/mL at baseline (quartiles: 6-15mg/mL) and 6mg/mL at follow-up (5-12mg/mL) (Wilcoxon signed rank test: W=5.2, p<0.001 for change over time). The median volume of e-liquid used per month was 80mL at baseline (quartiles: 50-130mL) and 100mL at follow-up (60-157mL, W=3.3, p=0.001 for change over time). CONCLUSION: In experienced e-cigarette users enrolled online, cotinine levels were similar to levels usually observed in cigarette smokers. Over time, these users decreased the concentration of nicotine in their e liquids, but increased their consumption of e-liquid in order to maintain their cotinine levels constant. PMID- 26804900 TI - Spatial and temporal trends in alcohol consumption in Belgian cities: A wastewater-based approach. AB - BACKGROUND: In recent years, scientific evidence has emerged that wastewater based epidemiology can deliver complementary information concerning the use of different substances of abuse. In this study, the potential of wastewater-based epidemiology in monitoring spatial and temporal trends in alcohol consumption in different populations in Belgium has been examined. METHODS: Concentrations of ethyl sulphate, a minor Phase-II metabolite of ethanol, in 163 influent wastewater samples from eight wastewater treatment plants in Belgium in the period 2013-2015 were measured with liquid chromatography coupled to tandem mass spectrometry and used to estimate alcohol consumption. RESULTS: The highest levels of alcohol consumption were detected in the metropoles Antwerp and Brussels compared to smaller villages. Annual variations were detected, with a higher alcohol consumption measured in 2013 compared with 2014. The weekly pattern showed a clear week and weekend difference in alcohol use, with intermediate levels on Monday and Friday. The results were extrapolated and a use of 5.6L pure alcohol per year per inhabitant aged 15+ has been estimated in Belgium. The comparison with available information on drinking habits of the Belgian population further demonstrated the usefulness of the wastewater-based epidemiology approach. CONCLUSIONS: This is the largest wastewater-based epidemiology study monitoring alcohol consumption to date, demonstrating that objective and quick information on spatio-temporal trends in alcohol consumption on a local and (inter)national scale can be obtained. PMID- 26804901 TI - Operon Gene Order Is Optimized for Ordered Protein Complex Assembly. AB - The assembly of heteromeric protein complexes is an inherently stochastic process in which multiple genes are expressed separately into proteins, which must then somehow find each other within the cell. Here, we considered one of the ways by which prokaryotic organisms have attempted to maximize the efficiency of protein complex assembly: the organization of subunit-encoding genes into operons. Using structure-based assembly predictions, we show that operon gene order has been optimized to match the order in which protein subunits assemble. Exceptions to this are almost entirely highly expressed proteins for which assembly is less stochastic and for which precisely ordered translation offers less benefit. Overall, these results show that ordered protein complex assembly pathways are of significant biological importance and represent a major evolutionary constraint on operon gene organization. PMID- 26804902 TI - Serum-Based Culture Conditions Provoke Gene Expression Variability in Mouse Embryonic Stem Cells as Revealed by Single-Cell Analysis. AB - Variation in gene expression is an important feature of mouse embryonic stem cells (ESCs). However, the mechanisms responsible for global gene expression variation in ESCs are not fully understood. We performed single-cell mRNA-seq analysis of mouse ESCs and uncovered significant heterogeneity in ESCs cultured in serum. We define highly variable gene clusters with distinct chromatin states and show that bivalent genes are prone to expression variation. At the same time, we identify an ESC-priming pathway that initiates the exit from the naive ESC state. Finally, we provide evidence that a large proportion of intracellular network variability is due to the extracellular culture environment. Serum-free culture reduces cellular heterogeneity and transcriptome variation in ESCs. PMID- 26804904 TI - Signaling from Mus81-Eme2-Dependent DNA Damage Elicited by Chk1 Deficiency Modulates Replication Fork Speed and Origin Usage. AB - Mammalian cells deficient in ATR or Chk1 display moderate replication fork slowing and increased initiation density, but the underlying mechanisms have remained unclear. We show that exogenous deoxyribonucleosides suppress both replication phenotypes in Chk1-deficient, but not ATR-deficient, cells. Thus, in the absence of exogenous stress, depletion of either protein impacts the replication dynamics through different mechanisms. In addition, Chk1 deficiency, but not ATR deficiency, triggers nuclease-dependent DNA damage. Avoiding damage formation through invalidation of Mus81-Eme2 and Mre11, or preventing damage signaling by turning off the ATM pathway, suppresses the replication phenotypes of Chk1-deficient cells. Damage and resulting DDR activation are therefore the cause, not the consequence, of replication dynamics modulation in these cells. Together, we identify moderate reduction of precursors available for replication as an additional outcome of DDR activation. We propose that resulting fork slowing, and subsequent firing of backup origins, helps replication to proceed along damaged templates. PMID- 26804903 TI - Mammalian Target of Rapamycin Complex 2 Controls CD8 T Cell Memory Differentiation in a Foxo1-Dependent Manner. AB - Upon infection, antigen-specific naive CD8 T cells are activated and differentiate into short-lived effector cells (SLECs) and memory precursor cells (MPECs). The underlying signaling pathways remain largely unresolved. We show that Rictor, the core component of mammalian target of rapamycin complex 2 (mTORC2), regulates SLEC and MPEC commitment. Rictor deficiency favors memory formation and increases IL-2 secretion capacity without dampening effector functions. Moreover, mTORC2-deficient memory T cells mount more potent recall responses. Enhanced memory formation in the absence of mTORC2 was associated with Eomes and Tcf-1 upregulation, repression of T-bet, enhanced mitochondrial spare respiratory capacity, and fatty acid oxidation. This transcriptional and metabolic reprogramming is mainly driven by nuclear stabilization of Foxo1. Silencing of Foxo1 reversed the increased MPEC differentiation and IL-2 production and led to an impaired recall response of Rictor KO memory T cells. Therefore, mTORC2 is a critical regulator of CD8 T cell differentiation and may be an important target for immunotherapy interventions. PMID- 26804905 TI - Diversity of the CD4 T Cell Alloresponse: The Short and the Long of It. AB - MHC alloantigen is recognized by two pathways: "directly," intact on donor cells, or "indirectly," as self-restricted allopeptide. The duration of each pathway, and its relative contribution to allograft vasculopathy, remain unclear. Using a murine model of chronic allograft rejection, we report that direct-pathway CD4 T cell alloresponses, as well as indirect-pathway responses against MHC class II alloantigen, are curtailed by rapid elimination of donor hematopoietic antigen presenting cells. In contrast, persistent presentation of epitope resulted in continual division and less-profound contraction of the class I allopeptide specific CD4 T cell population, with approximately 10,000-fold more cells persisting than following acute allograft rejection. This expanded population nevertheless displayed sub-optimal anamnestic responses and was unable to provide co-stimulation-independent help for generating alloantibody. Indirect-pathway CD4 T cell responses are heterogeneous. Appreciation that responses against particular alloantigens dominate at late time points will likely inform development of strategies aimed at improving transplant outcomes. PMID- 26804906 TI - Metabolic Reprogramming of Pancreatic Cancer Mediated by CDK4/6 Inhibition Elicits Unique Vulnerabilities. AB - Due to loss of p16ink4a in pancreatic ductal adenocarcinoma (PDA), pharmacological suppression of CDK4/6 could represent a potent target for treatment. In PDA models, CDK4/6 inhibition had a variable effect on cell cycle but yielded accumulation of ATP and mitochondria. Pharmacological CDK4/6 inhibitors induce cyclin D1 protein levels; however, RB activation was required and sufficient for mitochondrial accumulation. CDK4/6 inhibition stimulated glycolytic and oxidative metabolism and was associated with an increase in mTORC1 activity. MTOR and MEK inhibitors potently cooperate with CDK4/6 inhibition in eliciting cell-cycle exit. However, MTOR inhibition fully suppressed metabolism and yielded apoptosis and suppression of tumor growth in xenograft models. The metabolic state mediated by CDK4/6 inhibition increases mitochondrial number and reactive oxygen species (ROS). Concordantly, the suppression of ROS scavenging or BCL2 antagonists cooperated with CDK4/6 inhibition. Together, these data define the impact of therapeutics on PDA metabolism and provide strategies for converting cytostatic response to tumor cell killing. PMID- 26804908 TI - Dissecting the Roles of Divergent and Convergent Transcription in Chromosome Instability. AB - The interplay of transcription, topological tension, and chromosome breakage is a subject of intense interest, but, with so many facets to the problem, it is difficult to test. Here, we vary the orientation of promoters relative to one another in a yeast system that permits sensitive detection of chromosome breaks. Interestingly, convergent transcription that would direct RNA polymerases into one another does not increase chromosome breakage. In contrast, divergent transcription that would create underwound and potentially single-stranded DNA does cause a marked increase in chromosome breakage. Furthermore, we examine the role that topoisomerases are playing in preventing genome instability at these promoters and find that Top2 is required to prevent instability at converging promoters. PMID- 26804907 TI - Mps1 Mediated Phosphorylation of Hsp90 Confers Renal Cell Carcinoma Sensitivity and Selectivity to Hsp90 Inhibitors. AB - The molecular chaperone Hsp90 protects deregulated signaling proteins that are vital for tumor growth and survival. Tumors generally display sensitivity and selectivity toward Hsp90 inhibitors; however, the molecular mechanism underlying this phenotype remains undefined. We report that the mitotic checkpoint kinase Mps1 phosphorylates a conserved threonine residue in the amino-domain of Hsp90. This, in turn, regulates chaperone function by reducing Hsp90 ATPase activity while fostering Hsp90 association with kinase clients, including Mps1. Phosphorylation of Hsp90 is also essential for the mitotic checkpoint because it confers Mps1 stability and activity. We identified Cdc14 as the phosphatase that dephosphorylates Hsp90 and disrupts its interaction with Mps1. This causes Mps1 degradation, thus providing a mechanism for its inactivation. Finally, Hsp90 phosphorylation sensitizes cells to its inhibitors, and elevated Mps1 levels confer renal cell carcinoma selectivity to Hsp90 drugs. Mps1 expression level can potentially serve as a predictive indicator of tumor response to Hsp90 inhibitors. PMID- 26804909 TI - The Microcephaly-Associated Protein Wdr62/CG7337 Is Required to Maintain Centrosome Asymmetry in Drosophila Neuroblasts. AB - Centrosome asymmetry has been implicated in stem cell fate maintenance in both flies and vertebrates, but the underlying molecular mechanisms are incompletely understood. Here, we report that loss of CG7337, the fly ortholog of WDR62, compromises interphase centrosome asymmetry in fly neural stem cells (neuroblasts). Wdr62 maintains an active interphase microtubule-organizing center (MTOC) by stabilizing microtubules (MTs), which are necessary for sustained recruitment of Polo/Plk1 to the pericentriolar matrix (PCM) and downregulation of Pericentrin-like protein (Plp). The loss of an active MTOC in wdr62 mutants compromises centrosome positioning, spindle orientation, and biased centrosome segregation. wdr62 mutant flies also have an ~40% reduction in brain size as a result of cell-cycle delays. We propose that CG7337/Wdr62, a microtubule associated protein, is required for the maintenance of interphase microtubules, thereby regulating centrosomal Polo and Plp levels. Independent of this function, Wdr62 is also required for the timely mitotic entry of neural stem cells. PMID- 26804910 TI - L-selectin Is Essential for Delivery of Activated CD8(+) T Cells to Virus Infected Organs for Protective Immunity. AB - Cytotoxic CD8(+) T lymphocytes play a critical role in the host response to infection by viruses. The ability to secrete cytotoxic chemicals and cytokines is considered pivotal for eliminating virus. Of equal importance is how effector CD8(+) T cells home to virus-infected tissues. L-selectin has not been considered important for effector T cell homing, because levels are low on activated T cells. We report here that, although L-selectin expression is downregulated following T cell priming in lymph nodes, L-selectin is re-expressed on activated CD8(+) T cells entering the bloodstream, and recruitment of activated CD8(+) T cells from the bloodstream into virus-infected tissues is L-selectin dependent. Furthermore, L-selectin on effector CD8(+) T cells confers protective immunity to two evolutionally distinct viruses, vaccinia and influenza, which infect mucosal and visceral organs, respectively. These results connect homing and a function of virus-specific CD8(+) T cells to a single molecule, L-selectin. PMID- 26804911 TI - H2A.Z.1 Monoubiquitylation Antagonizes BRD2 to Maintain Poised Chromatin in ESCs. AB - Histone variant H2A.Z occupies the promoters of active and poised, bivalent genes in embryonic stem cells (ESCs) to regulate developmental programs, yet how it contributes to these contrasting states is poorly understood. Here, we investigate the function of H2A.Z.1 monoubiquitylation (H2A.Z.1ub) by mutation of the PRC1 target residues (H2A.Z.1(K3R3)). We show that H2A.Z.1(K3R3) is properly incorporated at target promoters in murine ESCs (mESCs), but loss of monoubiquitylation leads to de-repression of bivalent genes, loss of Polycomb binding, and faulty lineage commitment. Using quantitative proteomics, we find that tandem bromodomain proteins, including the BET family member BRD2, are enriched in H2A.Z.1 chromatin. We further show that BRD2 is gained at de repressed promoters in H2A.Z.1(K3R3) mESCs, whereas BRD2 inhibition restores gene silencing at these sites. Together, our study reveals an antagonistic relationship between H2A.Z.1ub and BRD2 to regulate the transcriptional balance at bivalent genes to enable proper execution of developmental programs. PMID- 26804912 TI - Single-Cell RNA-Sequencing Reveals a Continuous Spectrum of Differentiation in Hematopoietic Cells. AB - The transcriptional programs that govern hematopoiesis have been investigated primarily by population-level analysis of hematopoietic stem and progenitor cells, which cannot reveal the continuous nature of the differentiation process. Here we applied single-cell RNA-sequencing to a population of hematopoietic cells in zebrafish as they undergo thrombocyte lineage commitment. By reconstructing their developmental chronology computationally, we were able to place each cell along a continuum from stem cell to mature cell, refining the traditional lineage tree. The progression of cells along this continuum is characterized by a highly coordinated transcriptional program, displaying simultaneous suppression of genes involved in cell proliferation and ribosomal biogenesis as the expression of lineage specific genes increases. Within this program, there is substantial heterogeneity in the expression of the key lineage regulators. Overall, the total number of genes expressed, as well as the total mRNA content of the cell, decreases as the cells undergo lineage commitment. PMID- 26804913 TI - Extremely Long-Range Chromatin Loops Link Topological Domains to Facilitate a Diverse Antibody Repertoire. AB - Early B cell development is characterized by large-scale Igh locus contraction prior to V(D)J recombination to facilitate a highly diverse Ig repertoire. However, an understanding of the molecular architecture that mediates locus contraction remains unclear. We have combined high-resolution chromosome conformation capture (3C) techniques with 3D DNA FISH to identify three conserved topological subdomains. Each of these topological folds encompasses a major VH gene family that become juxtaposed in pro-B cells via megabase-scale chromatin looping. The transcription factor Pax5 organizes the subdomain that spans the VHJ558 gene family. In its absence, the J558 VH genes fail to associate with the proximal VH genes, thereby providing a plausible explanation for reduced VHJ558 gene rearrangements in Pax5-deficient pro-B cells. We propose that Igh locus contraction is the cumulative effect of several independently controlled chromatin subdomains that provide the structural infrastructure to coordinate optimal antigen receptor assembly. PMID- 26804914 TI - A CREB-Sirt1-Hes1 Circuitry Mediates Neural Stem Cell Response to Glucose Availability. AB - Adult neurogenesis plays increasingly recognized roles in brain homeostasis and repair and is profoundly affected by energy balance and nutrients. We found that the expression of Hes-1 (hairy and enhancer of split 1) is modulated in neural stem and progenitor cells (NSCs) by extracellular glucose through the coordinated action of CREB (cyclic AMP responsive element binding protein) and Sirt-1 (Sirtuin 1), two cellular nutrient sensors. Excess glucose reduced CREB-activated Hes-1 expression and results in impaired cell proliferation. CREB-deficient NSCs expanded poorly in vitro and did not respond to glucose availability. Elevated glucose also promoted Sirt-1-dependent repression of the Hes-1 promoter. Conversely, in low glucose, CREB replaced Sirt-1 on the chromatin associated with the Hes-1 promoter enhancing Hes-1 expression and cell proliferation. Thus, the glucose-regulated antagonism between CREB and Sirt-1 for Hes-1 transcription participates in the metabolic regulation of neurogenesis. PMID- 26804916 TI - Structural Insights into Divalent Cation Modulations of ATP-Gated P2X Receptor Channels. AB - P2X receptors are trimeric ATP-gated cation channels involved in physiological processes ranging widely from neurotransmission to pain and taste signal transduction. The modulation of the channel gating, including that by divalent cations, contributes to these diverse physiological functions of P2X receptors. Here, we report the crystal structure of an invertebrate P2X receptor from the Gulf Coast tick Amblyomma maculatum in the presence of ATP and Zn(2+) ion, together with electrophysiological and computational analyses. The structure revealed two distinct metal binding sites, M1 and M2, in the extracellular region. The M1 site, located at the trimer interface, is responsible for Zn(2+) potentiation by facilitating the structural change of the extracellular domain for pore opening. In contrast, the M2 site, coupled with the ATP binding site, might contribute to regulation by Mg(2+). Overall, our work provides structural insights into the divalent cation modulations of P2X receptors. PMID- 26804917 TI - Spatiotemporal Control of Forkhead Binding to DNA Regulates the Meiotic Gene Expression Program. AB - Meiosis is a differentiated program of the cell cycle that is characterized by high levels of recombination followed by two nuclear divisions. In fission yeast, the genetic program during meiosis is regulated at multiple levels, including transcription, mRNA stabilization, and splicing. Mei4 is a forkhead transcription factor that controls the expression of mid-meiotic genes. Here, we describe that Fkh2, another forkhead transcription factor that is essential for mitotic cell cycle progression, also plays a pivotal role in the control of meiosis. Fkh2 binding preexists in most Mei4-dependent genes, inhibiting their expression. During meiosis, Fkh2 is phosphorylated in a CDK/Cig2-dependent manner, decreasing its affinity for DNA, which creates a window of opportunity for Mei4 binding to its target genes. We propose that Fkh2 serves as a placeholder until the later appearance of Mei4 with a higher affinity for DNA that induces the expression of a subset of meiotic genes. PMID- 26804915 TI - A Mouse Model of X-linked Intellectual Disability Associated with Impaired Removal of Histone Methylation. AB - Mutations in a number of chromatin modifiers are associated with human neurological disorders. KDM5C, a histone H3 lysine 4 di- and tri-methyl (H3K4me2/3)-specific demethylase, is frequently mutated in X-linked intellectual disability (XLID) patients. Here, we report that disruption of the mouse Kdm5c gene recapitulates adaptive and cognitive abnormalities observed in XLID, including impaired social behavior, memory deficits, and aggression. Kdm5c knockout brains exhibit abnormal dendritic arborization, spine anomalies, and altered transcriptomes. In neurons, Kdm5c is recruited to promoters that harbor CpG islands decorated with high levels of H3K4me3, where it fine-tunes H3K4me3 levels. Kdm5c predominantly represses these genes, which include members of key pathways that regulate the development and function of neuronal circuitries. In summary, our mouse behavioral data strongly suggest that KDM5C mutations are causal to XLID. Furthermore, our findings suggest that loss of KDM5C function may impact gene expression in multiple regulatory pathways relevant to the clinical phenotypes. PMID- 26804918 TI - The PGC-1alpha/ERRalpha Axis Represses One-Carbon Metabolism and Promotes Sensitivity to Anti-folate Therapy in Breast Cancer. AB - Reprogramming of cellular metabolism plays a central role in fueling malignant transformation, and AMPK and the PGC-1alpha/ERRalpha axis are key regulators of this process. The intersection of gene-expression and binding-event datasets for breast cancer cells shows that activation of AMPK significantly increases the expression of PGC-1alpha/ERRalpha and promotes the binding of ERRalpha to its cognate sites. Unexpectedly, the data also reveal that ERRalpha, in concert with PGC-1alpha, negatively regulates the expression of several one-carbon metabolism genes, resulting in substantial perturbations in purine biosynthesis. This PGC 1alpha/ERRalpha-mediated repression of one-carbon metabolism promotes the sensitivity of breast cancer cells and tumors to the anti-folate drug methotrexate. These data implicate the PGC-1alpha/ERRalpha axis as a core regulatory node of folate cycle metabolism and further suggest that activators of AMPK could be used to modulate this pathway in cancer. PMID- 26804921 TI - The Histone Chaperone FACT Contributes to DNA Replication-Coupled Nucleosome Assembly. AB - DNA replication-coupled (RC) nucleosome assembly is mediated by histone chaperones and is fundamental for epigenetic inheritance and maintenance of genomic integrity. The mechanisms that promote this process are only partially understood. Here, we show that the histone chaperone FACT (facilitates chromatin transactions), consisting of Spt16 and Pob3, promotes newly synthesized histone H3-H4 deposition. We describe an allele of Spt16 (spt16-m) that has a defect in binding to H3-H4 and impairs their deposition onto DNA. Consistent with a direct role for FACT in RC nucleosome assembly, spt16-m displays synthetic defects with other histone chaperones associated with this process, CAF-1 and Rtt106. Importantly, we show that FACT physically associates with Rtt106 and that the acetylation of H3K56, a mark on newly synthesized H3, modulates this interaction. Therefore, FACT collaborates with CAF-1 and Rtt106 in RC nucleosome assembly. PMID- 26804919 TI - Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation. AB - The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of beta catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis. PMID- 26804920 TI - Detecting Microbial Dysbiosis Associated with Pediatric Crohn Disease Despite the High Variability of the Gut Microbiota. AB - The relationship between the host and its microbiota is challenging to understand because both microbial communities and their environments are highly variable. We have developed a set of techniques based on population dynamics and information theory to address this challenge. These methods identify additional bacterial taxa associated with pediatric Crohn disease and can detect significant changes in microbial communities with fewer samples than previous statistical approaches required. We have also substantially improved the accuracy of the diagnosis based on the microbiota from stool samples, and we found that the ecological niche of a microbe predicts its role in Crohn disease. Bacteria typically residing in the lumen of healthy individuals decrease in disease, whereas bacteria typically residing on the mucosa of healthy individuals increase in disease. Our results also show that the associations with Crohn disease are evolutionarily conserved and provide a mutual information-based method to depict dysbiosis. PMID- 26804922 TI - Unplanned intensive care unit admission after general anaesthesia in children: A single centre retrospective analysis. AB - OBJECTIVES: To determine the main causes for unplanned admission of children to the paediatric intensive care unit (PICU) following anaesthesia in our centre. To compare the results with previous publications and propose a data sheet for the prospective collection of such information. METHODS: Inclusion criteria were any patient under 16 years who had an unplanned post-anaesthetic admission to the PICU from 1999 to 2010 in our university hospital. Age, ASA score, type of procedure, origin and causes of the incident(s) that prompted admission and time of the admission decision were recorded. RESULTS: Out of a total of 44,559 paediatric interventions performed under anaesthesia during the study period, 85 were followed with an unplanned admission to the PICU: 67% of patients were younger than 5 years old. Their ASA status distribution from I to IV was 13, 47, 39 and 1%, respectively. The cause of admission was anaesthetic, surgical or mixed in 50, 37 and 13% of cases, respectively. The main causes of anaesthesia related admission were respiratory or airway management problems (44%) and cardiac catheterisation complications (29%). In 62%, the admission decision was taken in the operating room. CONCLUSION: Unplanned admission to the PICU after general anaesthesia is a rare event. In our series, most cases were less than 5 years old and were associated with at least one comorbidity. The main cause of admission was respiratory distress and the main type of procedure associated with admission was cardiac catheterisation. PMID- 26804924 TI - An improved preparation method for cross-sectional TEM specimens of films deposited on metallic substrates. AB - Cross-sectional TEM analysis is one of the most important techniques to characterize microstructures of films. However, the complex process, low efficiency, and low success rate of specimen preparation limit its application. This paper analyzed the main causes of low success rate and proposed an improved method for specimen preparation of films deposited on metallic substrates. This method consisting of twin-jet electropolishing and one-sided rocking ion milling is high in efficiency and success rate. PMID- 26804925 TI - Primary central nervous system gamma delta cytotoxic T-cell lymphoma. AB - Primary T-cell lymphomas of the central nervous system (CNS) are uncommon, but aggressive and increasing in incidence. We describe a rare case of T-cell lymphoma in a cerebellar location, to our knowledge the first reported case demonstrating gamma/delta receptor expression. Additionally, we elaborate on key diagnostic features and review all nine patients with primary CNS lymphoma of cytotoxic T-cell phenotype reported in the literature. A 26-year-old female medical student presented with a 6 week history of nausea, vomiting and dizziness. MRI revealed a 2 cm cerebellar mass. The tumor was subtotally resected, and pathologic examination of a subtotal resection specimen demonstrated peripheral T-cell lymphoma, not otherwise specified, with a gamma/delta cytotoxic T-cell phenotype. She subsequently started high dose methotrexate and cytarabine. We report a unique case of primary CNS gamma delta CD8+ T-cell lymphoma lineage in a young female patient. While these are rare entities, it is an important differential diagnosis to consider. Therapy should be tailored to the patient, and involves resection with adjuvant chemotherapy, radiotherapy or autologous stem-cell based treatments. PMID- 26804923 TI - Structures of the E. coli translating ribosome with SRP and its receptor and with the translocon. AB - Co-translational protein targeting to membranes is a universally conserved process. Central steps include cargo recognition by the signal recognition particle and handover to the Sec translocon. Here we present snapshots of key co translational-targeting complexes solved by cryo-electron microscopy at near atomic resolution, establishing the molecular contacts between the Escherichia coli translating ribosome, the signal recognition particle and the translocon. Our results reveal the conformational changes that regulate the latching of the signal sequence, the release of the heterodimeric domains of the signal recognition particle and its receptor, and the handover of the signal sequence to the translocon. We also observe that the signal recognition particle and the translocon insert-specific structural elements into the ribosomal tunnel to remodel it, possibly to sense nascent chains. Our work provides structural evidence for a conformational state of the signal recognition particle and its receptor primed for translocon binding to the ribosome-nascent chain complex. PMID- 26804926 TI - The effect of pomegranate juice on clinical signs, matrix metalloproteinases and antioxidant status in patients with knee osteoarthritis. AB - BACKGROUND: Osteoarthritis (OA) is one of the commonest forms of musculoskeletal disorders that leads to joint degeneration and has a major impact on patients' quality of life. Experimental and in vitro studies have suggested the protective roles of pomegranate juice (PJ) as a rich antioxidant source for mitigating cartilage inflammation. In this interventional study, 38 patients with knee OA were randomly divided into two groups: PJ or control for 6 weeks to evaluate the effect of this intervention on clinical signs, inflammation and antioxidant status. RESULTS: Significant decreases in Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) total score (P = 0.01), stiffness score (P = 0.00) and physical function score (P = 0.01) were observed in PJ group after the intervention. The means of serum levels of matrix metalloproteinase (MMP)-13 was significantly decreased (P = 0.02) and glutathione peroxidase was increased in the intervention group compared with the control group after the study period (P = 0.02). CONCLUSIONS: According to the findings of this clinical trial, PJ consumption can improve physical function and stiffness, decrease breakdown cartilage enzymes and increase antioxidant status in patients with knee OA. (c) 2016 Society of Chemical Industry. PMID- 26804927 TI - Oral drug dosage forms administered to hospitalized children: Analysis of 117,665 oral administrations in a French paediatric hospital over a 1-year period. AB - Selecting the most appropriate dosage form, that ensures safe administration and adherence of medications, is a major issue for children. Marketed drugs, however, have rarely been tested for their use in children. There is a need for more data on drug formulations administered to children to identify unmet needs, and drive future paediatric research. We observed, over a 12-month follow-up, 117,665 oral drug administrations to 1998 hospitalized children. Nine-tenths belonged to five Anatomical Therapeutic Chemical classes: Alimentary tract & metabolism, Nervous system, Cardiovascular system, Anti-infectives for systemic use and Blood & blood forming organs, one third of drug doses administered to school-age children and adolescents were liquids, and extemporaneous capsules were commonly used in younger children. Our study shows that despite the advantages of solid dosage forms and recent evidence from randomized controlled trials showing their acceptability in infants, they are seldom used in paediatric practice. PMID- 26804928 TI - Comparison of manually crimping and laser-activated nitinol prosthesis in otosclerosis surgery: our experience of 98 patients. PMID- 26804929 TI - Tailoring Multilayered BiVO4 Photoanodes by Pulsed Laser Deposition for Water Splitting. AB - Pulsed laser deposition (PLD) is proposed as promising technique for the fabrication of multilayered BiVO4-based photoanodes. For this purpose, bare BiVO4 films and two heterojunctions, BiVO4/SnO2 and BiVO4/WO3/SnO2, have been prepared using consecutive ablation of assorted targets in a single batch. The ease, high versatility and usefulness of this technique in engineering the internal configuration of the photoanode with stoichiometric target-to-substrate transfer are demonstrated. The obtained photocurrent densities are among the highest reported values for undoped BiVO4 without oxygen evolution catalysts (OEC). A detailed analysis of the influence of SnO2 and WO3 layers on the charge transport properties because of the changes at the internal FTO/semiconductor interface is performed through transient photocurrent measurements (TPC), showing that the BiVO4/WO3/SnO2 heterostructure attains a significant decrease in the internal losses and reaches high photocurrent values. This study is expected to open the door to the fabrication of other systems based on ternary (or even more complex) metal oxides as photoanodes for water splitting, which is a promising alternative for obtaining materials able to fulfill the different requierements in the development of more efficient systems for this process. PMID- 26804930 TI - A microfluidic indirect competitive immunoassay for multiple and sensitive detection of testosterone in serum and urine. AB - We demonstrate a microfluidic-based indirect competitive chemiluminescence enzyme immunoassay (MIC) for multiple, sensitive, reliable and rapid detection of testosterone in human serum and urine samples. As MIC can detect biomarkers in a cost-effective and easy-to-operate manner, it may have great potential for clinical diagnosis and point-of-care testing (POCT). PMID- 26804931 TI - Life After Bariatric Surgery: Perceptions of Male Patients and Their Intimate Relationships. AB - This study explores the experiences of 20 men who have had bariatric surgery, focusing on their couple or marital relationships. The researcher concentrates on men's perspectives regarding relationship satisfaction, sexual intimacy, and social support after surgical intervention. Phenomenology and family systems theory were used to guide the study from which emerged three themes: (a) Unintended consequences (unpredicted problems occurring within intimate relationships); (b) Intimacy as bittersweet (experiencing increasing levels of intimacy, while still desiring more); and (c) Inconsistent social support (experiencing instances where social support is provided, while simultaneously experiencing other areas where social support is not provided). The study includes a rich description of the data, critical analysis, and discussion of clinical implications for therapists and other healthcare professionals. PMID- 26804932 TI - Selective oxidation of trimethylolpropane to 2,2-bis(hydroxymethyl)butyric acid using growing cells of Corynebacterium sp. ATCC 21245. AB - Multifunctional chemicals including hydroxycarboxylic acids are gaining increasing interest due to their growing applications in the polymer industry. One approach for their production is a biological selective oxidation of polyols, which is difficult to achieve by conventional chemical catalysis. In the present study, trimethylolpropane (TMP), a trihydric alcohol, was subjected to selective oxidation using growing cells of Corynebacterium sp. ATCC 21245 as a biocatalyst and yielding the dihydroxy-monocarboxylic acid, 2,2-bis(hydroxymethyl)butyric acid (BHMB). The study revealed that co-substrates are crucial for this reaction. Among the different evaluated co-substrates, a mixture of glucose, xylose and acetate at a ratio of 5:5:2 was found optimum. The optimal conditions for biotransformation were pH 8, 1v/v/m airflow and 500rpm stirring speed. In batch mode of operation, 70.6% of 5g/l TMP was converted to BHMB in 10 days. For recovery of the product the adsorption pattern of BHMB to the anion exchange resin, Ambersep((r)) 900 (OH(-)), was investigated in batch and column experiments giving maximum static and dynamic binding capacities of 135 and 144mg/g resin, respectively. BHMB was separated with 89.7% of recovery yield from the fermentation broth. The approach is applicable for selective oxidation of other highly branched polyols by biotransformation. PMID- 26804934 TI - Surficial Siloxane-to-Silanol Interconversion during Room-Temperature Hydration/Dehydration of Amorphous Silica Films Observed by ATR-IR and TIR-Raman Spectroscopy. AB - Silica has been frequently studied using infrared and Raman spectroscopy due to its importance in many practical contexts where its surface chemistry plays a vital role. The majority of these studies have utilized chemical-vapor-deposited films in vacuo after high-temperature calcination. However, room-temperature hydration and dehydration of thin silica particle films has not been well characterized in spite of the importance of such films as substrates for polymer and surfactant adsorption. The present study has utilized ATR-IR spectroscopy and thin silica particle films exposed to varying humidity to clearly show reversible conversion between surface siloxanes and hydrogen-bonded silanols without the need for semiempirical peak deconvolution. The IR spectra from corresponding hydration experiments on deuterated silica films has confirmed the vibrational mode assignments. The variation of humidity over silica films formed from silica suspensions of differing pH gave IR spectra consistent with the change in the relative populations of siloxide to silanol surface groups. In addition, total internal reflection Raman spectroscopy has been used to provide further evidence of room-temperature dehydroxylation, with spectral evidence for the presence of three-membered siloxane rings when films are dehydrated under argon. The confirmation of room-temperature siloxane-to-silanol interconversion is expected to benefit understanding in many silica surface chemical contexts. PMID- 26804933 TI - Discovery of the Aryl-phospho-indole IDX899, a Highly Potent Anti-HIV Non nucleoside Reverse Transcriptase Inhibitor. AB - Here, we describe the design, synthesis, biological evaluation, and identification of a clinical candidate non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a novel aryl-phospho-indole (APhI) scaffold. NNRTIs are recommended components of highly active antiretroviral therapy (HAART) for the treatment of HIV-1. Since a major problem associated with NNRTI treatment is the emergence of drug resistant virus, this work focused on optimization of the APhI against clinically relevant HIV-1 Y181C and K103N mutants and the Y181C/K103N double mutant. Optimization of the phosphinate aryl substituent led to the discovery of the 3-Me,5-acrylonitrile-phenyl analogue RP-13s (IDX899) having an EC50 of 11 nM against the Y181C/K103N double mutant. PMID- 26804935 TI - Size-controllable synthesis of Bi/Bi2O3 heterojunction nanoparticles using pulsed Nd:YAG laser deposition and metal-semiconductor-heterojunction-assisted photoluminescence. AB - We synthesized Bi/Bi2O3 heterojunction nanoparticles at various substrate temperatures using the pulsed laser deposition (PLD) technique with a pulsed Nd:YAG laser. The Bi/Bi2O3 heterojunction nanoparticles consisted of Bi nanoparticles and Bi2O3 surface layers. The average diameter of the Bi nanoparticles and the thickness of the Bi2O3 surface layer are linearly proportional to the substrate temperature. The heterojunctions between the Bi nanoparticles and Bi2O3 surface layers, which are the metal-semiconductor heterojunctions, can strongly enhance the photoluminescence (PL) of the Bi/Bi2O3 nanoparticles, because the metallic Bi nanoparticles can provide massive free Fermi-level electrons for the electron transitions in the Bi2O3 surface layers. The enhancement of PL emission at room temperature by metal-semiconductor heterojunctions make the Bi/Bi2O3 heterojunction nanoparticles potential candidates for use in optoelectronic nanodevices, such as light-emitting diodes (LEDs) and laser diodes (LDs). PMID- 26804936 TI - Sense of coherence, self-regulated learning and academic performance in first year nursing students: A cluster analysis approach. AB - This paper examines the relationship between nursing students' sense of coherence, self-regulated learning and academic performance in bioscience. While there is increasing recognition of a need to foster students' self-regulated learning, little is known about the relationship of psychological strengths, particularly sense of coherence and academic performance. Using a prospective, correlational design, 563 first year nursing students completed the three dimensions of sense of coherence scale - comprehensibility, manageability and meaningfulness, and five components of self-regulated learning strategy - elaboration, organisation, rehearsal, self-efficacy and task value. Cluster analysis was used to group respondents into three clusters, based on their sense of coherence subscale scores. Although there were no sociodemographic differences in sense of coherence subscale scores, those with higher sense of coherence were more likely to adopt self-regulated learning strategies. Furthermore, academic grades collected at the end of semester revealed that higher sense of coherence was consistently related to achieving higher academic grades across all four units of study. Students with higher sense of coherence were more self-regulated in their learning approach. More importantly, the study suggests that sense of coherence may be an explanatory factor for students' successful adaptation and transition in higher education, as indicated by the positive relationship of sense of coherence to academic performance. PMID- 26804937 TI - Identifying gaps for research prioritisation: Global burden of external causes of injury as reflected in the Cochrane Database of Systematic Reviews. AB - IMPORTANCE: Burden of disease should impact research prioritisation. OBJECTIVE: To analyse the Cochrane Database of Systematic Reviews (CDSR) and determine whether systematic reviews and protocols accurately represent disease burden, as measured by disability-adjusted life years (DALYs) from the Global Burden of Disease (GBD) 2010 Study. METHODS: Two investigators collected GBD disability metrics for 12 external causes of injury in the GBD 2010 Study. These external causes were then assessed for systematic review and protocol representation in CDSR. Data was collected during the month of April 2015. There were no study participants aside from the researchers. Percentage of total 2010 DALYs, 2010 DALY rank, and median DALY percent change from 1990 to 2010 of the 12 external causes of injury were compared with CDSR representation of systematic reviews and protocols. Data were analysed for correlation using Spearman rank correlation. RESULTS: Eleven of the 12 causes were represented by at least one systematic review or protocol in CDSR; the category collective violence and legal intervention had no representation in CDSR. Correlation testing revealed a strong positive correlation that was statistically significant. Representation of road injury; interpersonal violence; fire, heat, and hot substances; mechanical forces; poisonings, adverse effect of medical treatment, and animal contact was well aligned with respect to DALY. Representation of falls was greater compared to DALY, while self-harm, exposure to forces of nature, and other transport injury representation was lower compared to DALY. CONCLUSIONS AND RELEVANCE: CDSR representation of external causes of injury strongly correlates with disease burden. The number of systematic reviews and protocols was well aligned for seven out of 12 causes of injury. These results provide high-quality and transparent data that may guide future prioritisation decisions. PMID- 26804938 TI - The thickness of proximal lateral femoral wall. PMID- 26804939 TI - Influence of plate material and screw design on stiffness and ultimate load of locked plating in osteoporotic proximal humeral fractures. AB - INTRODUCTION: The main purpose was to compare the biomechanical properties of a carbon-fibre reinforced polyetheretherketone (CF-PEEK) composite locking plate with pre-existing data of a titanium-alloy plate when used for fixation of an unstable 2-part fracture of the surgical neck of the humerus. The secondary purpose was to compare the mechanical behaviour of locking bolts and conventional locking cancellous screws. METHODS: 7 pairs of fresh frozen human humeri were allocated to two equal groups. All specimens were fixed with the CF-PEEK plate. Cancellous screws (PEEK/screw) were compared to locking bolts (PEEK/bolt) for humeral head fixation. Stiffness, fracture gap deflection and ultimate load as well as load before screw perforation of the articular surface were assessed. Results were compared between groups and with pre-existing biomechanical data of a titanium-alloy plate. RESULTS: The CF-PEEK plate featured significantly lower stiffness compared to the titanium-alloy plate (P<0.001). In ultimate load testing, 6 out of 14 CF-PEEK plates failed due to irreversible deformation and cracking. No significant difference was observed between results of groups PEEK/screw and PEEK/bolt (P>0.05). DISCUSSION: The CF-PEEK plate has more elastic properties and significantly increases movement at the fracture site of an unstable proximal humeral fracture model compared to the commonly used titanium alloy plate. The screw design however does neither affect the constructs primary mechanical behaviour in the constellation tested nor the load before screw perforation. PMID- 26804940 TI - The evidence for 'flipping out': A systematic review of the flipped classroom in nursing education. AB - BACKGROUND: The flipped classroom has generated interest in higher education providing a student-centred approach to learning. This has the potential to engage nursing students in ways that address the needs of today's students and the complexity of contemporary healthcare. Calls for educational reform, particularly in healthcare programs such as nursing, highlight the need for students to problem-solve, reason and apply theory into practice. The drivers towards student-based learning have manifested in team, problem and case-based learning models. Though there has been a shift towards the flipped classroom, comparatively little is known about how it is used in nursing curricula. OBJECTIVES: The aims of this systematic review were to examine how the flipped classroom has been applied in nursing education and outcomes associated with this style of teaching. DATA SOURCES: Five databases were searched and resulted in the retrieval of 21 papers: PubMed, CINAHL, EMBASE, Scopus and ERIC. REVIEW METHODS: After screening for inclusion/exclusion criteria, each paper was evaluated using a critical appraisal tool. Data extraction and analysis were completed on all included studies. RESULTS: This systematic review screened 21 titles and abstracts resulting in nine included studies. All authors critically appraised the quality of the included studies. Five studies were identified and themes identified were: academic performance outcomes, and student satisfaction implementing the flipped classroom. CONCLUSIONS: Use of the flipped classroom in higher education nursing programmes yielded neutral or positive academic outcomes and mixed results for satisfaction. Engagement of students in the flipped classroom model was achieved when academics informed and rationalised the purpose of the flipped classroom model to students. However, no studies in this review identified the evaluation of the process of implementing the flipped classroom. Studies examining the process and ongoing evaluation and refinement of the flipped classroom in higher education nursing programmes are warranted. PMID- 26804941 TI - Development and application of course-embedded assessment system for program outcome evaluation in the Korean nursing education: A pilot study. AB - BACKGROUND: Program outcome evaluation is important because it is an indicator for good quality of education. Course-embedded assessment is one of the program outcome evaluation methods. However, it is rarely used in Korean nursing education. OBJECTIVES: The study purpose was to develop and apply preliminarily a course-embedded assessment system to evaluate one program outcome and to share our experiences. DESIGN AND SETTINGS: This was a methodological study to develop and apply the course-embedded assessment system based on the theoretical framework in one nursing program in South Korea. DATA: Scores for 77 students generated from the three practicum courses were used. METHODS: The course embedded assessment system was developed following the six steps suggested by Han's model as follows. 1) One program outcome in the undergraduate program, "nursing process application ability", was selected and 2) the three clinical practicum courses related to the selected program outcome were identified. 3) Evaluation tools including rubric and items were selected for outcome measurement and 4) performance criterion, the educational goal level for the program, was established. 5) Program outcome was actually evaluated using the rubric and evaluation items in the three practicum courses and 6) the obtained scores were analyzed to identify the achievement rate, which was compared with the performance criterion. RESULTS: Achievement rates for the selected program outcome in adult, maternity, and pediatric nursing practicum were 98.7%, 100%, and 66.2% in the case report and 100% for all three in the clinical practice, and 100%, 100%, and 87% respectively for the conference. These are considered as satisfactory levels when compared with the performance criterion of "at least 60% or more". CONCLUSION: Course-embedded assessment can be used as an effective and economic method to evaluate the program outcome without running an integrative course additionally. Further studies to develop course-embedded assessment systems for other program outcomes in nursing education are needed. PMID- 26804943 TI - Efficacy of proactive long-term maintenance therapy of canine atopic dermatitis with 0.0584% hydrocortisone aceponate spray: a double-blind placebo controlled pilot study. AB - BACKGROUND: Long-term remission between flares of canine atopic dermatitis (CAD) can be difficult to achieve. Therefore, additional strategic forms of treatment are needed in order to target flare prevention. The concept of proactive therapy is recommended in the European guidelines for the treatment of human atopic eczema. OBJECTIVES: To evaluate the efficacy of a proactive treatment regimen with a 0.0584% hydrocortisone aceponate (HCA) spray for CAD. ANIMALS: Client owned dogs with spontaneous atopic dermatitis (AD) (n = 41). METHODS: This pilot study was conducted as a randomised, placebo-controlled, double-blinded clinical trial with an end-point of treatment failure. Dogs were treated once daily to remission, then randomly assigned to receive either the HCA spray (n = 21) or a placebo (n = 20) spray on two consecutive days each week. All dogs were on appropriate flea control. No topical or systemic anti-inflammatory or antimicrobial agents were permitted. Intention-to-treat analysis was used. RESULTS: At Day 0, all the dogs were in remission or had mild AD based on their Canine Atopic Dermatitis Extent and Severity Index, version 3 (CADESI-03) scores. The time to relapse was significantly higher in the HCA group (median 115 d; range 31-260 d) compared to the placebo group (median 33 d; range 15-61 d) (P < 0.0001). No adverse events were attributable to the HCA spray. Four dogs were lost to follow-up and four were withdrawn after receiving prohibited medication. CONCLUSIONS AND CLINICAL IMPORTANCE: These results indicate that proactive long term therapy of CAD with an HCA spray administered on two consecutive days each week is effective and well-tolerated. PMID- 26804947 TI - Radical C-H arylations of (hetero)arenes catalysed by gallic acid. AB - Gallic acid efficiently catalyses radical arylations in water-acetone at room temperature. This methodology proved to be versatile and scalable. Therefore, it constitutes a greener alternative to arylation. Moreover, considering that gallic acid is an abundant vegetable tannin, this work also unleashes an alternative method for the reutilisation of bio-wastes. PMID- 26804945 TI - Developmental variations in the impact of intimate partner violence exposure during childhood. AB - BACKGROUND: Intimate partner violence (IPV) is a pervasive problem impacting individuals around the globe. The consequences of IPV extend beyond the adults in the relationship, as children witness a significant proportion of such violence. Exposure to IPV during childhood has devastating effects across multiple domains of functioning. METHODS: This article reviews empirical studies of the effects of exposure to IPV by developmental stage. RESULTS: The psychological, social, physical, and cognitive consequences of witnessing IPV are examined across development; from the impact of prenatal exposure to effects in infancy and toddlerhood, the preschool years, school-aged children, and adolescence. CONCLUSIONS: The review concludes by providing suggestions for future research based on the identified developmental variations, recommendations for developmentally-sensitive interventions for children who have witnessed IPV, and directions for policy to address the issue of violence exposure early in the lives of children. PMID- 26804946 TI - Acute kidney injury: current concepts and new insights. AB - BACKGROUND: Acute kidney injury, which was previously named as acute renal failure, is a complex clinical disorder and continues to be associated with poor outcomes. It is frequently seen in hospitalized patients, especially in critically ill patients. The primary causes of acute kidney injury are divided into three categories: prerenal, intrinsic renal and postrenal. The definition and staging of acute kidney injury are mainly based on the risk, injury, failure, loss, end-stage kidney disease (RIFLE) criteria and the acute kidney injury network (AKIN) criteria, which have previously been defined. However the clinical utility of these criteria is still uncertain. Several biomarkers such as Cystatin C and neutrophil gelatinase-associated lipocalin have been suggested for the diagnosis, severity classification and most importantly, the modification of outcome in acute kidney injury. METHODS: Current literature on the definition, biomarkers, management and epidemiology of acute kidney injury was reviewed by searching keywords in Medline and PubMed databases. RESULTS: The epidemiology, pathophysiology and diagnosis of acute kidney injury were discussed. The clinical implications of novel biomarkers and management of acute kidney injury were also discussed. CONCLUSIONS: The current definitions of acute kidney injury are based on the RIFLE, AKIN and KDIGO criteria. Although these criteria have been widely validated, some of limitations are still remain. Since acute kidney injury is common and harmful, all preventive measures should be taken to avoid its occurrence. Currently, there is no a definitive role for novel biomarkers. PMID- 26804948 TI - Self-esteem discrepancies and identity-expressive consumption: Evidence from Norwegian adolescents. AB - Prior research established that simultaneously holding discrepant explicit (deliberate, controlled) and implicit (automatic, uncontrolled) self-esteem gives rise to self-enhancing behaviours. Given that individuals tend to enhance their self-concepts with brands that are associated with positive identities, this study examined whether self-esteem discrepancy was related to the extent to which individuals developed connections with brands that are associated with their in groups. Findings from an adolescent sample (ages 16-18) indicated that adolescents with larger discrepancies between explicit and implicit self-esteem were more likely to construct their self-concepts using in-group-linked brands. PMID- 26804949 TI - Leadership for palliative nursing: an optional extra? PMID- 26804950 TI - The use of corticosteroids in reducing cancer-related fatigue: assessing the evidence for clinical practice. AB - Fatigue is a significant issue for people with advanced cancer, impacting on quality of life. Strategies to address fatigue encompass non-pharmacological and pharmacological approaches and thus require a multidisciplinary approach to manage the physical and psychological impacts on the individual. A widely used strategy to treat fatigue in palliative care is the use of corticosteroids but, despite being frequently prescribed, evidence of their effectiveness is ambiguous. This paper used a systematic approach to explore literature to determine evidence about whether the use of corticosteroids improves levels of cancer-related fatigue in people with advanced cancer. Some 12 relevant papers were found, of which all but 4 were excluded because of age, or because the population group was receiving active treatment. All studies reported improvements in patient-reported fatigue as a result of taking corticosteroids, although the quality of results varied and only a few were deemed to have statistically significant results. While there is some evidence that corticosteroids can improve cancer-related fatigue, more rigorous research is required. PMID- 26804951 TI - Treating cancer pain: the palliative nursing dilemma. PMID- 26804952 TI - Measuring delirium point-prevalence in two Australian palliative care inpatient units. AB - BACKGROUND: Internationally, delirium prevalence in palliative care is reported to range between 26-88%, yet little is known about the occurrence of delirium in Australian palliative care inpatient populations. AIMS: To: 1) ascertain 24-hour delirium point-prevalence in an Australian palliative care inpatient population; 2) test the feasibility and acceptability of the delirium measurement methodology. METHODS: This was a prospective cross-sectional study. Delirium was measured in patients of two palliative care units using the Nursing Delirium Screening Scale, Memorial Delirium Assessment Scale and DSM-5 diagnostic criteria. Descriptive statistics were used to report patient demographics, palliative care phase, function, delirium measure completion, and proportion of patients with a positive screen and diagnosis. RESULTS: Patients (n=47) had a mean age of 74 years (SD+10) and mostly malignant diagnoses (96%). All patients were screened for delirium, but few were capable of completing the Memorial Delirium Assessment Scale (n=2). One-third of patients (34%) screened positive for delirium and 19% were diagnosed as delirious according to the DSM-5. CONCLUSION: The Nursing Delirium Screening Scale and physician application of DSM 5 proved feasible and acceptable, while the Memorial Delirium Assessment Scale did not. Patients' advanced age and proportions screening positive for delirium and diagnosed as delirious attest to the need to rapidly recognise, assess and respond to patients experiencing this distressing disorder while being cared for in palliative care inpatient settings. PMID- 26804953 TI - Reflections of a team approach to involving people with dementia in research. AB - The article reflects on the ways in which a person-centred approach was used to ensure that people with dementia were given an opportunity to participate in research. The authors discuss three key issues-the importance of including people with dementia in research, informed consent and the possibility of accidental disclosure of diagnosis. The study was an in-depth examination of the ways in which the cancer team manages patients with memory problems and patients with dementia, and the experiences of these patients and their families in accessing outpatient cancer treatment and care in Wales. The study findings will be reported elsewhere. This article aims to add to the small body of existing knowledge within the literature that describes the experiences of researchers in actively involving people with dementia in research. PMID- 26804954 TI - Factors influencing attitude toward care of dying patients in first-year nursing students. AB - AIM: To describe Swedish first-year undergraduate nursing students' attitudes toward care of dying patients. Possible influences such as age, earlier care experiences, care education, experiences of meeting dying patients and place of birth were investigated. METHOD: The Frommelt Attitude Toward Care of the Dying Scale (FATCOD) was used in six universities. Descriptive statistics and regression analysis were used. RESULTS: Some 371 students (67.3%) reported overall positive attitude toward caring for dying patients (total mean FATCOD 119.5, SD 10.6) early in their first semester. Older students, students with both earlier care experience and earlier education, those with experience of meeting a dying person, and students born in Sweden reported the highest scores, a more positive attitude. CONCLUSION: Age, earlier care experience and education, experiences of meeting a dying person and place of birth seems to affect students' attitudes toward care of the dying and need to be considered among nursing educators. PMID- 26804955 TI - Quality of life in patients with malignant spinal cord compression: a review of evidence-based literature. AB - Malignant spinal cord compression (MSCC) is a devastating complication of metastatic cancer. The majority of existing studies focus on treatment guidelines for MSCC, with little emphasis on the impact that MSCC has on quality of life (QoL) for this patient group. This literature review aims to critically appraise available literature focusing on QoL for patients with MSCC. Relevant literature was identified from key electronic databases. A dearth of credible studies representative of the patient population with MSCC was found. Thematic analysis was used as a guide to identify key themes that impact on QoL. Interestingly, patients with MSCC generally report good QoL and low levels of distress in over 50% of cases. However, a significant percentage of patients are distressed. The review concludes that increased awareness and further research into the impact of MSCC is required. PMID- 26804957 TI - Politics and palliative care: Azores. PMID- 26804959 TI - TO SEE OURSELVES AS OTHERS SEE US!: RELATIONS AMONG SELF-PERCEPTIONS, PEER PERCEPTIONS, AND EXPECTED PEER-PERCEPTIONS OF PERSONALITY. AB - Past research claims to demonstrate (a) widespread intercultural agreement on the social desirability of personality test items, and (b) that a priori scaling of an item on this presumably universal social desirability continuum is highly predictive of the probability of its endorsement. These notions are challenged by present findings which show (1) widespread disagreement among nominally identified groups within a single culture as to the desirabilities of a sample of commonly used personality items, and (2) substantial inconsistency of a social desirability wale values to predict individual endorsement probabilities. Implications for best construction are discussed, particularly concerning the use of forced-choice formats for personality inventories. PMID- 26804960 TI - CROSS-VALIDATIONAL EVIDENCE ON THE DIMENSIONS OF PROBLEM BEHAVIOR IN THE EARLY GRADES. AB - One hundred forty-seven children in the first through the third grades were rated by their teachers on a behavior problem inventory employed in previous studies. The data were subjected to a principal axis factor analysis and rotated to an oblique position. Congruence coefficients were computed among the twelve factors resulting from the current analysis, and the eight factors extracted in an earlier study. Six of the factor matches were significant at or beyond the .O1 level. Five of these matches had a sufficient number of salient variables common to the two studies. The five dimensions meeting the consideration of significance of congruence across samples and sufficient common salients were termed, in an earlier study, Hyperactivity, Sluggishness, Paranoid Tendencies, Social Withdrawal, and Acting Out. The evidence of the predictive validity of these was briefly discussed. PMID- 26804961 TI - MULTIVARIATE ANALYSIS OF CONCEPTS INDUCED FROM BOUNDED PREDICATIVE VALUE STATEMENTS. AB - A conceptual domain was sampled by eliciting own-words statements from 267 college atudents with a domain-bunding question-What is a bad thing to do? Bath respondent produced 10 predicative examples (descriptions of behavior he thought belonged in the domain) but could explicitly disqualify no idea. From the elicited statements, E induced a set of internally consistent, mutually exclusive, emergent concepts by putting statements together that, in E's judgment, said or meant the same thing. 11 different indices of interconcept association (across persons) were tested and evaluated. A 73-concept matrix of association indices was factor-analyzed. Concepts were progressively excluded by objective rules until an interpretable, simple-struoture solution was obtained wit41 31 concepts, comprising 62% of the data. PMID- 26804962 TI - TWO WAY FIXED EFFECTS ANALYSIS OF VARIANCE WITH DISPROPORTIONATE CELL FREQUENCIES. AB - Three general types of solutions are considered for the 2-way fixed effects ANOVA with disproportionate cell frequencies. PMID- 26804963 TI - A NEW METHODOLOGICAL REVISION OF EKMAN'S CONTENT MODEL OF MULTIDIMENSIONAL SIMILARITY ANALYSIS. AB - A new methodological revision to Ekman's content model of multi- dimensional similarity analysis is proposed. Whereas Ekman factor analyzes matrices of mean similarity estimates, the Stone-Coles revision involves the factor analysis of correlational similarities obtained by intercorrelating all column vectors of an Ekman mean similarity matrix. The method proposed solves certain mathematical objections to the Ekman model. 14 investigations of multidimensional similarity conducted by Ekman and his associates were reanalyzed from the Stone-Coles correlational similarity approach. A compari- son of the results indicate that this new methodological construct yields interpretable factorial descriptions of the judged similarity of stimulus-objects which are more meaningful and more parsimonious than the results yielded by the Elanan methodology. PMID- 26804964 TI - INDIVIDUAL DIFFERENCES IN PERCEIVED TRAIT RELATIONSHIPS AS A FUNCTION OF DIMENSIONAL SALIENCE. AB - Two studies were conducted to examine the applicability of Carroll and Chang's INDSCAL model to trait similarity data. The model assumes that all individuals use the same configuration of dimensions in making perceptual judgments but differ in the weight or salience of each dimension. In the two studies correlations of .81 and .71 were obtained between the 4-dimensional INDSCAL solutions and subjects' scalar products data. High canonical correlations were found between the INDSCAL stimulus dimensions and those obtained by Kruskal's non metric procedure. Results also indicated that the dimensions obtained using 20 traits were closely comparable to those obtained when the same traits were embedded in the context of 60 other traits. Clustering subjects on the basis of their dimensional salience profiles yielded five groups which were distinguished by patiterns of dimensional relationships on three discriminant factors. PMID- 26804965 TI - Successful Use of the "Peripheral IJ". PMID- 26804967 TI - Single dose sublingual testosterone and oral sildenafil vs. a dual route/dual release fixed dose combination tablet: a pharmacokinetic comparison. AB - AIM: The aim was to compare the pharmacokinetic profiles of two formulations of a combination drug product containing 0.5 mg testosterone and 50 mg sildenafil for female sexual interest/arousal disorder. The prototype (formulation 1) consists of a testosterone solution for sublingual administration and a sildenafil tablet that is administered 2.5 h later. The dual route/dual release fixed dose combination tablet (formulation 2) employs a sublingual and an oral route for systemic uptake. This tablet has an inner core of sildenafil with a polymeric time delay coating and an outer polymeric coating containing testosterone. It was designed to increase dosing practicality and decrease potential temporal non adherence through circumventing the relatively complex temporal dosing scheme. METHODS: Twelve healthy premenopausal subjects received both formulations randomly on separate days. Blood was sampled frequently to determine the pharmacokinetics of free testosterone, total testosterone, dihydrotestosterone, sildenafil and N-desmethyl-sildenafil. RESULTS: Formulation 2 had a higher maximum concentration (Cmax ) for testosterone, 8.06 ng ml(-1) (95% confidence interval [CI] 6.84, 9.28) and higher area under the plasma concentration-time curve (AUC), 7.69 ng ml(-1) h (95% CI 6.22, 9.16) than formulation 1, 5.66 ng ml(-1) (95% CI 4.63, 6.69) and 5.12 ng ml(-1) h (95% CI 4.51, 5.73), respectively. Formulation 2 had a lower Cmax for sildenafil, 173 ng ml(-1) (95% CI 126, 220) and a lower AUC, 476 ng ml(-1) h (95% CI 401, 551) than formulation 1, 268 ng ml(-1) (95% CI 188, 348) and 577 ng ml(-1) h (95% CI 462, 692), respectively. Formulation 2 released sildenafil after 2.75 h (95% CI 2.40, 3.10). CONCLUSIONS: The dual route/dual release fixed dose combination tablet fulfilled its design criteria and is considered suitable for further clinical testing. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Female sexual interest/arousal disorder (FSIAD) is a significant problem impacting psychological well-being, but the pharmacotherapeutic options for this problem are lacking. The combined, on demand, sublingual administration of low dose sublingual testosterone and oral administration of sildenafil is a novel pharmacotherapeutic option under development for FSIAD. In proof-of-concept trials, these compounds were successfully administered via different dosage forms (sublingual and oral) at different time points (separated by 2.5 h) because of their markedly different pharmacokinetic-pharmacodynamic profiles. For future larger scale studies and the clinical practice, this raises obvious adherence issues. WHAT THIS STUDY ADDS: A newly developed dual route/dual release fixed dose combination tablet containing testosterone and sildenafil mimics the pharmacokinetic profile of these components when they are administered as different dosage forms, 2.5 h apart. This combination tablet is a suitable final pharmaceutical drug product that will be used in future studies. PMID- 26804969 TI - Short dental implants versus standard dental implants placed in the posterior jaws: A systematic review and meta-analysis. AB - OBJECTIVE: The purpose of the present systematic review and meta-analysis was to compare short implants (equal or less than 8mm) versus standard implants (larger than 8mm) placed in posterior regions of maxilla and mandible, evaluating survival rates of implants, marginal bone loss, complications and prosthesis failures. DATA: This review has been registered at PROSPERO under the number CRD42015016588. Main search terms were used in combination: dental implant, short implant, short dental implants, short dental implants posterior, short dental implants maxilla, and short dental implants mandible. SOURCE: An electronic search for data published up until September/2015 was undertaken using the PubMed/Medline, Embase and The Cochrane Library databases. STUDY SELECTION: Eligibility criteria included clinical human studies, randomized controlled trials and/or prospective studies, which evaluated short implants in comparison to standard implants in the same study. CONCLUSION: The search identified 1460 references, after inclusion criteria 13 studies were assessed for eligibility. A total of 1269 patients, who had received a total of 2631 dental implants. The results showed that there was no significant difference of implants survival (P=.24; RR:1.35; CI: 0.82-2.22), marginal bone loss (P=.06; MD: -0.20; CI: -0.41 to 0.00), complications (P=.08; RR:0.54; CI: 0.27-1.09) and prosthesis failures (P=.92; RR:0.96; CI: 0.44-2.09). Short implants are considered a predictable treatment for posterior jaws. However, short implants with length less than 8 mm (4-7 mm) should be used with caution because they present greater risks to failures compared to standard implants. CLINICAL SIGNIFICANCE: Short implants are frequently placed in the posterior area in order to avoid complementary surgical procedures. However, clinicians need to be aware that short implants with length less than 8mm present greater risk of failures. PMID- 26804970 TI - Associations between peripheral androgens and cortisol in infertile women. AB - Testosterone has in recent years been proven essential for normal growth and maturation of small growing follicles. Concomitantly, low functional ovarian reserve (LFOR), characterized by a small growing follicle pool, has been associated with low testosterone levels, which can be of ovarian and/or adrenal origin. In this study we, therefore, investigated whether peripheral sex steroid precursors and testosterone levels potentially reflect on adrenal function. In a retrospective cohort study of 355 consecutive infertile women, who presented to an academically affiliated fertility center in New York City, we investigated in a series of statistical models whether low peripheral sex steroid precursors and testosterone are associated with peripheral cortisol (C) levels, reflecting adrenal function. To determine potential correlations, we investigated the dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione (AD), total testosterone (TT), free testosterone (FT); sex hormone binding globulin (SHBG), anti-Mullerian hormone (AMH), thyroid stimulating hormone (TSH) and C in a series of multivariate and logistic regression analyses, utilizing C either as a continuous variable or with cut off <5.0MUg/dL, and TT only as a continuous variable. Practically all models demonstrated significant predictability of peripheral sex hormone precursors for C levels, with DHEA demonstrating the strongest and most consistent predictability as an individual parameter and as part of the DHEAS/DHEA ratio. We conclude that in infertile women peripheral sex hormone precursors, especially DHEA, reflect C levels and, therefore, adrenal function. In infertile women, at all ages low levels of sex hormone precursors, therefore, should be considered indications for further adrenal assessments. PMID- 26804971 TI - Percutaneous transilial pinning for treatment of seventh lumbar vertebral body fracture. A retrospective analysis of 17 cases. AB - OBJECTIVE: To evaluate outcomes after percutaneous application of transilial pinning in dogs with seventh lumbar vertebral body fracture with concurrent lumbosacral luxation. METHODS: We reviewed the medical records of dogs with seventh lumbar vertebral body fracture stabilized with percutaneous transilial pinning that were treated at our hospital between January 2000 and March 2014. Radiographic measurements were used for comparing craniocaudal and ventrodorsal displacement pre- and postoperatively. RESULTS: Seventeen dogs met the inclusion criteria. The neurological status of the majority of treated dogs improved quickly, with immediate pain reduction after surgery. Implants were well tolerated throughout the application period and were removed at a mean time of 54.4 +/- 9.2 days. One dog experienced a major complication (implant failure) and required surgical revision a week after the initial procedure. Minor complications included pin-tract inflammation, signs of back pain lasting five weeks and acute lameness after implant removal. Postoperative radiographic measurements showed shortening of the vertebral body and residual dorsoventral dislocation. Otherwise, functional recovery was good (5 of 17 dogs) to excellent (10 of 17 dogs) in the majority of the patients. CLINICAL RELEVANCE: The use of two percutaneous transilial pins can be considered as treatment for the management of seventh lumbar fracture-luxation in dogs. Our modified stabilization technique is relatively easy to perform; less invasive on the soft tissues; and uses implants that are versatile, modifiable, and easily removable. PMID- 26804972 TI - Coping strategies and mental health outcomes of conflict-affected persons in the Republic of Georgia. AB - AIMS: Adults who experienced the 1992 and 2008 armed conflicts in the Republic of Georgia were exposed to multiple traumatic events and stressors over many years. The aim was to investigate what coping strategies are used by conflict-affected persons in Georgia and their association with mental disorders. METHOD: A cross sectional survey was conducted with 3600 adults, representing internally displaced persons (IDPs) from conflicts in the 1990s (n = 1200) and 2008 (n = 1200) and former IDPs who returned to their homes after the 2008 conflict (n = 1200). Post-traumatic stress disorder, depression, anxiety and coping strategies were measured using the Trauma Screening Questionnaire, Patient Health Questionnaire-9, Generalised Anxiety and adapted version of the Brief Coping Inventory, respectively. Descriptive and multivariate regression analyses were used. RESULTS: Coping strategies such as use of humour, emotional support, active coping, acceptance and religion were significantly associated with better mental health outcomes. Coping strategies of behavioural and mental disengagement, denial, venting emotions, substance abuse and gambling were significantly associated with poorer mental health outcomes. The reported use of coping strategies varied significantly between men and women for 8 of the 15 strategies addressed. CONCLUSIONS: Many conflict-affected persons in Georgia are still suffering mental health problems years after the conflicts. A number of specific coping strategies appear to be associated with better mental health and should be encouraged and supported where possible. PMID- 26804973 TI - How do differential explanations of voice-hearing influence attributions and behavioral intentions towards voice-hearers? AB - Explanations regarding the etiology of mental health difficulties have been found to affect public attitudes towards those who experience such difficulties. Utilizing a large, randomized parallel-groups design (N=1004), we examined how standardized differential explanations of voice-hearing influence public attitudes, attributions, and behavioral intentions towards voice-hearers. Additionally, we incorporated a behavioral outcome measure to examine whether reported behavioral intentions towards voice-hearers were related to responses towards an individual with a history of voice-hearing. Consistent with attribution theory, mediated pathways between attributions and intentions were identified: broadly, viewing the voice-hearer's behavior as dangerous, within their personal responsibility, and global was associated with more coercive intentions - and these were mediated by feelings of fear, anger, and pity. Reported behavioral intentions demonstrated small-to-moderate associations with our behavioral outcome measure. The findings suggest that explanations regarding the etiology of mental health difficulties that seek to reduce public attributions of dangerousness, personal responsibility, and globality may facilitate more helpful responses towards voice-hearers. PMID- 26804974 TI - Psychophysiological decoupling in alexithymic pain disorder patients. AB - Considering that impaired coping with stress is closely linked with emergence of stress-sensitive disorders most notably in alexithymic individuals, we conducted the first study examining stress-related autonomic reactivity in alexithymic pain disorder patients. Twenty-one pain disorder patients with high and an equivalent patient group with low alexithymia scores were exposed to three types of affect inductive stimuli with variable affective involvement: arithmetic task, watching arousing video material and giving an oral presentation. Subjective appraisal of the induced emotional experience and physiological reactivity (heart rate, muscle tension and skin conductance) was documented. During oral presentation high alexithymia patients showed significantly lower skin conductance in combination with increased subjective negative affect compared to low alexithymia patients. Our results thus demonstrate a decoupling between physiological and affect processing in pain disorder patients with high alexithymia during a stressful situation that was subjectively associated with negative affect. PMID- 26804975 TI - Phosphoserine phosphatase activity is elevated and correlates negatively with plasma d-serine concentration in patients with schizophrenia. AB - The pathophysiology of schizophrenia may involve N-methyl-D-aspartate receptor (NMDAR) hypofunction. D-3serine and glycine are endogenous l-serine-derived NMDAR co-agonists. We hypothesized that the l-serine synthesis pathway could be involved in schizophrenia. We measured the activity of phosphoserine phosphatase (PSP), a rate-limiting enzyme in l-serine synthesis, in peripheral blood mononuclear cells of 54 patients with schizophrenia and 49 normal control subjects. Plasma amino acid (l-serine, d-serine, glycine, glutamine, and glutamate) levels were measured by high performance liquid chromatography. Peripheral blood mRNA expression levels of PHGDH, PSAT1, PSP, and SR, determined by quantitative real-time PCR were compared between patients and controls. PSP activity was higher in patients than in controls, especially in male patients. In male patients, the plasma l-serine concentration was higher than that in controls. In patients, PSP activity was negatively correlated with plasma d serine and glycine levels. Furthermore, PSP activity was positively correlated with plasma l-serine concentration. These results were statistically significant only in male patients. PSP, PSAT1, and PHGDH mRNA levels were lower in patients than in controls, except when the PHGDH expression level was compared with ACTB expression. In summary, we found the l-serine synthesis system to be altered in patients with schizophrenia, especially in male patients. PMID- 26804976 TI - Differential Binding of Rimantadine Enantiomers to Influenza A M2 Proton Channel. AB - Rimantadine hydrochloride (alpha-methyl-1-adamantane-methalamine hydrochloride) is a chiral compound which exerts antiviral activity against the influenza A virus by inhibiting proton conductance of the M2 ion channel. In complex with M2, rimantadine has always been characterized as a racemic mixture. Here, we report the novel enantioselective synthesis of deuterium-labeled (R)- and (S) rimantadine and the characterization of their protein-ligand interactions using solid-state NMR. Isotropic chemical shift changes strongly support differential binding of the enantiomers to the proton channel. Position restrained simulations satisfying distance restraints from (13)C-(2)H rotational-echo double-resonance NMR show marked differences in the hydrogen-bonding pattern of the two enantiomers at the binding site. Together these results suggest a complex set of interactions between (R)-rimantadine and the M2 proton channel, leading to a higher stability for this enantiomer of the drug in the channel pore. PMID- 26804977 TI - Semantic interrogation of a multi knowledge domain ontological model of tendinopathy identifies four strong candidate risk genes. AB - Tendinopathy is a multifactorial syndrome characterised by tendon pain and thickening, and impaired performance during activity. Candidate gene association studies have identified genetic factors that contribute to intrinsic risk of developing tendinopathy upon exposure to extrinsic factors. Bioinformatics approaches that data-mine existing knowledge for biological relationships may assist with the identification of candidate genes. The aim of this study was to data-mine functional annotation of human genes and identify candidate genes by ontology-seeded queries capturing the features of tendinopathy. Our BioOntological Relationship Graph database (BORG) integrates multiple sources of genomic and biomedical knowledge into an on-disk semantic network where human genes and their orthologs in mouse and rat are central concepts mapped to ontology terms. The BORG was used to screen all human genes for potential links to tendinopathy. Following further prioritisation, four strong candidate genes (COL11A2, ELN, ITGB3, LOX) were identified. These genes are differentially expressed in tendinopathy, functionally linked to features of tendinopathy and previously implicated in other connective tissue diseases. In conclusion, cross domain semantic integration of multiple sources of biomedical knowledge, and interrogation of phenotypes and gene functions associated with disease, may significantly increase the probability of identifying strong and unobvious candidate genes in genetic association studies. PMID- 26804978 TI - Application of Site-Specific Spin Labeling for NMR Detecting Inhibitor-Induced Conformational Change of HIV-1 Reverse Transcriptase. AB - Paramagnetism-assisted nuclear magnetic resonance (NMR) techniques can provide long-range structural information complemented with local information derived from chemical-shift perturbation and nuclear Overhauser effect data. Here, we address the application of paramagnetic relaxation enhancement (PRE) to detect inhibitor-induced conformational change of a drug target protein using human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) as a model protein. Using a site-specific spin-labeled HIV-1 RT mutant with selective (13) C labeling, conformation-dependent PREs were successfully observed reflecting the stabilization of an open conformation of this enzyme caused by inhibitor binding. This study demonstrates that the paramagnetism-assisted NMR approach offers an alternative strategy in protein-based drug screening to identify allosteric inhibitors of a target protein. PMID- 26804979 TI - Clinical, mechanical, and immunohistopathological effects of tissue adhesives on the colon: An in-vivo study. AB - BACKGROUND: Tissue adhesives may be useful for sealing bowel anastomoses by preventing anastomotic leakage. Prior to clinical implementation, an in-depth analysis of the clinical and immunohistopathological effects of tissue adhesives on the target tissue and of the mechanical strength of the adhesive bond in an in vivo model is needed. MATERIALS AND METHODS: In 84 rats, two bowel segments were glued using one of the following tissue adhesive: Bioglue, Gelatin-resorcinol formaldehyde (GRF), Glubran 2, Histoacryl Flex, Omnex, Duraseal Xact, or Tissucol. Rats were followed for 7 or 28 days. Endpoints were clinical complication rate, mechanical strength, and immunohistopathological reactions. RESULTS: Of the seven tissue adhesives, GRF and Bioglue showed the highest rates of bowel wall destruction and ileus and the most severe immunohistopathological tissue reactions at 7 and 28 days. Cyanoacrylates (Histoacryl Flex, Omnex, Glubran 2) showed high mechanical strength and mild immunohistopathological reactions at 7 and 28 days. Duraseal Xact and Tissucol were the most inert tissue adhesives, but exhibited low mechanical strength. At 28 days, mechanical strength was significantly correlated to CD8, CD68, and Ki67 cell counts. CONCLUSION: Based on the clinical and immunohistopathological outcomes, GRF and Bioglue were found to be the least suitable tissue adhesives for colonic use. Duraseal Xact and Tissucol were inert but also showed low mechanical strength. Cyanoacrylates exhibited mild clinical and immunohistopathological effects while maintaining high strength, which makes them promising as colonic sealants. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 846-854, 2017. PMID- 26804980 TI - Low-Temperature Solution Synthesis of Few-Layer 1T '-MoTe2 Nanostructures Exhibiting Lattice Compression. AB - Molybdenum ditelluride, MoTe2 , is emerging as an important transition-metal dichalcogenide (TMD) material because of its favorable properties relative to other TMDs. The 1T ' polymorph of MoTe2 is particularly interesting because it is semimetallic with bands that overlap near the Fermi level, but semiconducting 2H MoTe2 is more stable and therefore more accessible synthetically. Metastable 1T ' MoTe2 forms directly in solution at 300 degrees C as uniform colloidal nanostructures that consist of few-layer nanosheets, which appear to exhibit an approx. 1 % lateral lattice compression relative to the bulk analogue. Density functional theory calculations suggest that small grain sizes and polycrystallinity stabilize the 1T ' phase in the MoTe2 nanostructures and suppress its transformation back to the more stable 2H polymorph through grain boundary pinning. Raman spectra of the 1T '-MoTe2 nanostructures exhibit a laser energy dependence, which could be caused by electronic transitions. PMID- 26804982 TI - Essential role of proteasomes in maintaining self-renewal in neural progenitor cells. AB - Protein turnover and homeostasis are regulated by the proteasomal system, which is critical for cell function and viability. Pluripotency of stem cells also relies on normal proteasomal activity that mitigates senescent phenotypes induced by intensive cell replications, as previously demonstrated in human bone marrow stromal cells. In this study, we investigated the role of proteasomes in self renewal of neural progenitor cells (NPCs). Through both in vivo and in vitro analyses, we found that the expression of proteasomes was progressively decreased during aging. Likewise, proliferation and self-renewal of NPCs were also impaired in aged mice, suggesting that the down-regulation of proteasomes might be responsible for this senescent phenotype. Lowering proteasomal activity by loss of-function manipulations mimicked the senescence of NPCs both in vitro and in vivo; conversely, enhancing proteasomal activity restored and improved self renewal in aged NPCs. These results collectively indicate that proteasomes work as a key regulator in promoting self-renewal of NPCs. This potentially provides a promising therapeutic target for age-dependent neurodegenerative diseases. PMID- 26804984 TI - Association of rumen fill score and energy status during the close-up dry period with conception at first artificial insemination in dairy cows. AB - Recent studies have shown significant associations between prepartum energy status and postpartum fertility in dairy cows; therefore, the assessment of energy status by blood metabolites and metabolic hormones and suitable improvement of management during the prepartum period may enhance reproductive performance. Rumen fill score (RFS) is associated with feed intake; however, it is unknown whether RFS is also related to blood parameters. Therefore, this study investigated the relationship between RFS and energy status during the prepartum period, and their associations with conception at first artificial insemination (AI) after parturition. In 42 multiparous Holstein cows, RFS assessment and blood sampling were carried out twice a week during 3 weeks of the peripartum period. Ovarian cycles until AI were evaluated by measuring milk progesterone levels. Before calving, positive correlations were observed between RFS and total cholesterol, and RFS did not change in pregnant cows at first AI after parturition, whereas in non-pregnant cows, RFS decreased gradually as the calving day approached. After calving, non-pregnant cows showed lower energy status compared with pregnant cows, and some non-pregnant cows showed anovulation and cessation of estrous cycle. In conclusion, RFS during the close-up dry period is related to real-time energy status, and is associated with postpartum energy status and conception at first AI in dairy cows. (c) 2016 Japanese Society of Animal Science. PMID- 26804985 TI - Insight into the role of histidine in RNR motif of protein component of RNase P of M. tuberculosis in catalysis. AB - RNase P, a ribonucleoprotein endoribonuclease, is involved in the 5' end processing of pre-tRNAs, with its RNA component being the catalytic subunit. It is an essential enzyme. All bacterial RNase Ps have one RNA and one protein component. A conserved RNR motif in bacterial RNase P protein components is involved in their interaction with the RNA component. In this work, we have reconstituted the RNase P of M. tuberculosis in vitro and investigated the role of a histidine in the RNR motif in its catalysis. We expressed the protein and RNA components of mycobacterial RNase P in E. coli, purified them, and reconstituted the holoenzyme in vitro. The histidine in RNR motif was mutated to alanine and asparagine by site-directed mutagenesis. The RNA component alone showed activity on pre-tRNA(ala) substrate at high magnesium concentrations. The RNA and protein components associated together to manifest catalytic activity at low magnesium concentrations. The histidine 67 in the RNR motif of M. tuberculosis RNase P protein component was found to be important for the catalytic activity and stability of the enzyme. Generally, the RNase P of M. tuberculosis functions like other bacterial enzymes. The histidine in the RNR motif of M. tuberculosis appears to be able to substitute optimally for asparagine found in the majority of the protein components of other bacterial RNase P enzymes. PMID- 26804983 TI - Identification of A3 adenosine receptor agonists as novel non-narcotic analgesics. AB - Chronic pain negatively impacts the quality of life in a variety of patient populations. The current therapeutic repertoire is inadequate in managing patient pain and warrants the development of new therapeutics. Adenosine and its four cognate receptors (A1 , A2A , A2B and A3 ) have important roles in physiological and pathophysiological states, including chronic pain. Preclinical and clinical studies have revealed that while adenosine and agonists of the A1 and A2A receptors have antinociceptive properties, their therapeutic utility is limited by adverse cardiovascular side effects. In contrast, our understanding of the A3 receptor is only in its infancy, but exciting preclinical observations of A3 receptor antinociception, which have been bolstered by clinical trials of A3 receptor agonists in other disease states, suggest pain relief without cardiovascular side effects and with sufficient tolerability. Our goal herein is to briefly discuss adenosine and its receptors in the context of pathological pain and to consider the current data regarding A3 receptor-mediated antinociception. We will highlight recent findings regarding the impact of the A3 receptor on pain pathways and examine the current state of selective A3 receptor agonists used for these studies. The adenosine-to-A3 receptor pathway represents an important endogenous system that can be targeted to provide safe, effective pain relief from chronic pain. PMID- 26804987 TI - Functional identification of a GORK potassium channel from the ancient desert shrub Ammopiptanthus mongolicus (Maxim.) Cheng f. AB - KEY MESSAGE: A GORK homologue K(+) channel from the ancient desert shrub Ammopiptanthus mongolicus (Maxim.) Cheng f. shows the functional conservation of the GORK channels among plant species. Guard cell K(+) release through the outward potassium channels eventually enables the closure of stomata which consequently prevents plant water loss from severe transpiration. Early patch clamp studies with the guard cells have revealed many details of such outward potassium currents. However, genes coding for these potassium-release channels have not been sufficiently characterized from species other than the model plant Arabidopsis thaliana. We report here the functional identification of a GORK (for Gated or Guard cell Outward Rectifying K(+) channels) homologue from the ancient desert shrub Ammopiptanthus mongolicus (Maxim.) Cheng f. AmGORK was primary expressed in shoots, where the transcripts were regulated by stress factors simulated by PEG, NaCl or ABA treatments. Patch-clamp measurements on isolated guard cell protoplasts revealed typical depolarization voltage gated outward K(+) currents sensitive to the extracelluar K(+) concentration and pH, resembling the fundamental properties previously described in other species. Two-electrode voltage-clamp analysis in Xenopus lavies oocytes with AmGORK reconstituted highly similar characteristics as assessed in the guard cells, supporting that the function of AmGORK is consistent with a crucial role in mediating stomatal closure in Ammopiptanthus mongolicus. Furthermore, a single amino acid mutation D297N of AmGORK eventually abolishes both the voltage-gating and its outward rectification and converts the channel into a leak-like channel, indicating strong involvement of this residue in the gating and voltage dependence of AmGORK. Our results obtained from this anciently originated plant support a strong functional conservation of the GORK channels among plant species and maybe also along the progress of revolution. PMID- 26804988 TI - Sex, Gender, and Traumatic Brain Injury: A Commentary. AB - The goal of this supplemental issue is to address major knowledge, research, and clinical practice gaps regarding the limited focus on brain injury in girls and women as well as limited analysis of the effect of sex and gender in research on acquired brain injury. Integrating sex and gender in research is recognized as leading to better science and, ultimately, to better clinical practice. A sex and gender analytical approach to rehabilitation research is crucial to understanding traumatic brain injury and improving quality of life outcomes for survivors. Put another way, the lack of focus on sex and gender reduces the rigor of research design, the generalizability of study findings, and the effectiveness of clinical implementation and knowledge dissemination practices. The articles in this supplement examine sex and gender using a variety of methodological approaches and research contexts. Recommendations for future research on acquired brain injury that consciously incorporates sex and gender are made throughout this issue. This supplement is a product of the Girls and Women with ABI Task Force of the American Congress of Rehabilitation Medicine. PMID- 26804989 TI - Visual Cue-Discriminative Dopaminergic Control of Visuomotor Transformation and Behavior Selection. AB - Animals behave differently in response to visual cues with distinct ethological meaning, a process usually thought to be achieved through differential visual processing. Using a defined zebrafish escape circuit as a model, we found that behavior selection can be implemented at the visuomotor transformation stage through a visually responsive dopaminergic-inhibitory circuit module. In response to non-threatening visual stimuli, hypothalamic dopaminergic neurons and their positively regulated hindbrain inhibitory interneurons increase activity, suppressing synaptic transmission from the visual center to the escape circuit. By contrast, threatening visual stimuli inactivate some of these neurons, resulting in dis-inhibition of the visuomotor transformation and escape generation. The distinct patterns of dopaminergic-inhibitory neural module's visual responses account for this stimulus-specific visuomotor transformation and behavioral control. Thus, our study identifies a behavioral relevance-dependent mechanism that controls visuomotor transformation and behavior selection and reveals that neuromodulation can be tuned by visual cues to help animals generate appropriate responses. PMID- 26804990 TI - Rabies Virus CVS-N2c(DeltaG) Strain Enhances Retrograde Synaptic Transfer and Neuronal Viability. AB - Virally based transsynaptic tracing technologies are powerful experimental tools for neuronal circuit mapping. The glycoprotein-deletion variant of the SAD-B19 vaccine strain rabies virus (RABV) has been the reagent of choice in monosynaptic tracing, since it permits the mapping of synaptic inputs to genetically marked neurons. Since its introduction, new helper viruses and reagents that facilitate complementation have enhanced the efficiency of SAD-B19(DeltaG) transsynaptic transfer, but there has been little focus on improvements to the core RABV strain. Here we generate a new deletion mutant strain, CVS-N2c(DeltaG), and examine its neuronal toxicity and efficiency in directing retrograde transsynaptic transfer. We find that by comparison with SAD-B19(DeltaG), the CVS N2c(DeltaG) strain exhibits a reduction in neuronal toxicity and a marked enhancement in transsynaptic neuronal transfer. We conclude that the CVS N2c(DeltaG) strain provides a more effective means of mapping neuronal circuitry and of monitoring and manipulating neuronal activity in vivo in the mammalian CNS. PMID- 26804991 TI - Postsynaptic Plasticity Triggered by Ca2+-Permeable AMPA Receptor Activation in Retinal Amacrine Cells. AB - Amacrine cells are thought to be a major locus for mechanisms of light adaptation and contrast enhancement in the retina. However, the potential for plasticity in their AMPA receptor currents remains largely unknown. Using paired patch-clamp recordings between bipolar cell terminals and amacrine cells, we have simultaneously measured presynaptic membrane capacitance changes and EPSCs. Repetitive bipolar cell depolarizations, designed to maintain the same amount of exocytosis, nevertheless significantly potentiated evoked EPSCs in a subpopulation of amacrine cells. Likewise, repetitive iontophoresis (or puffs) of glutamate (or AMPA) onto the dendrites of amacrine cells also significantly potentiated evoked currents and [Ca(2+)]i rises. However, strong postsynaptic Ca(2+) buffering with BAPTA abolished the potentiation and selective antagonists of Ca(2+)-permeable AMPA receptors also blocked the potentiation of AMPA-mediated currents. Together these results suggest that Ca(2+) influx via Ca(2+)-permeable AMPA receptors can elicit a rapid form of postsynaptic plasticity in a subgroup of amacrine cell dendrites. PMID- 26804992 TI - Neural Mechanisms of Post-error Adjustments of Decision Policy in Parietal Cortex. AB - Humans often slow down after mistakes (post-error slowing [PES]), but the neural mechanism and adaptive role of PES remain controversial. We studied changes in the neural mechanisms of decision making after errors in humans and monkeys that performed a motion direction discrimination task. We found that PES is mediated by two factors: a reduction in sensitivity to sensory information and an increase in the decision bound. Both effects are implemented through dynamic changes in the decision-making process. Neuronal responses in the monkey lateral intraparietal area revealed that bound changes are implemented by decreasing an evidence-independent urgency signal. They also revealed a reduction in the rate of evidence accumulation, reflecting reduced sensitivity. These changes in the bound and sensitivity provide a quantitative account of choices and response times. We suggest that PES reflects an adaptive increase of decision bound in anticipation of maladaptive reductions in sensitivity to incoming evidence. PMID- 26804993 TI - Phosphoproteomics of the Dopamine Pathway Enables Discovery of Rap1 Activation as a Reward Signal In Vivo. AB - Dopamine (DA) type 1 receptor (D1R) signaling in the striatum presumably regulates neuronal excitability and reward-related behaviors through PKA. However, whether and how D1Rs and PKA regulate neuronal excitability and behavior remain largely unknown. Here, we developed a phosphoproteomic analysis method to identify known and novel PKA substrates downstream of the D1R and obtained more than 100 candidate substrates, including Rap1 GEF (Rasgrp2). We found that PKA phosphorylation of Rasgrp2 activated its guanine nucleotide-exchange activity on Rap1. Cocaine exposure activated Rap1 in the nucleus accumbens in mice. The expression of constitutively active PKA or Rap1 in accumbal D1R-expressing medium spiny neurons (D1R-MSNs) enhanced neuronal firing rates and behavioral responses to cocaine exposure through MAPK. Knockout of Rap1 in the accumbal D1R-MSNs was sufficient to decrease these phenotypes. These findings demonstrate a novel DA PKA-Rap1-MAPK intracellular signaling mechanism in D1R-MSNs that increases neuronal excitability to enhance reward-related behaviors. PMID- 26804994 TI - Cux1 Enables Interhemispheric Connections of Layer II/III Neurons by Regulating Kv1-Dependent Firing. AB - Neuronal subtype-specific transcription factors (TFs) instruct key features of neuronal function and connectivity. Activity-dependent mechanisms also contribute to wiring and circuit assembly, but whether and how they relate to TF-directed neuronal differentiation is poorly investigated. Here we demonstrate that the TF Cux1 controls the formation of the layer II/III corpus callosum (CC) projections through the developmental transcriptional regulation of Kv1 voltage-dependent potassium channels and the resulting postnatal switch to a Kv1-dependent firing mode. Loss of Cux1 function led to a decrease in the expression of Kv1 transcripts, aberrant firing responses, and selective loss of CC contralateral innervation. Firing and innervation were rescued by re-expression of Kv1 or postnatal reactivation of Cux1. Knocking down Kv1 mimicked Cux1-mediated CC axonal loss. These findings reveal that activity-dependent processes are central bona fide components of neuronal TF-differentiation programs and establish the importance of intrinsic firing modes in circuit assembly within the neocortex. PMID- 26804995 TI - Pathway-Specific Striatal Substrates for Habitual Behavior. AB - The dorsolateral striatum (DLS) is implicated in habit formation. However, the DLS circuit mechanisms underlying habit remain unclear. A key role for DLS is to transform sensorimotor cortical input into firing of output neurons that project to the mutually antagonistic direct and indirect basal ganglia pathways. Here we examine whether habit alters this input-output function. By imaging cortically evoked firing in large populations of pathway-defined striatal projection neurons (SPNs), we identify features that strongly correlate with habitual behavior on a subject-by-subject basis. Habitual behavior correlated with strengthened DLS output to both pathways as well as a tendency for action-promoting direct pathway SPNs to fire before indirect pathway SPNs. In contrast, habit suppression correlated solely with a weakened direct pathway output. Surprisingly, all effects were broadly distributed in space. Together, these findings indicate that the striatum imposes broad, pathway-specific modulations of incoming activity to render learned motor behaviors habitual. PMID- 26804996 TI - IGF-1 Receptor Differentially Regulates Spontaneous and Evoked Transmission via Mitochondria at Hippocampal Synapses. AB - The insulin-like growth factor-1 receptor (IGF-1R) signaling is a key regulator of lifespan, growth, and development. While reduced IGF-1R signaling delays aging and Alzheimer's disease progression, whether and how it regulates information processing at central synapses remains elusive. Here, we show that presynaptic IGF-1Rs are basally active, regulating synaptic vesicle release and short-term plasticity in excitatory hippocampal neurons. Acute IGF-1R blockade or transient knockdown suppresses spike-evoked synaptic transmission and presynaptic cytosolic Ca(2+) transients, while promoting spontaneous transmission and resting Ca(2+) level. This dual effect on transmitter release is mediated by mitochondria that attenuate Ca(2+) buffering in the absence of spikes and decrease ATP production during spiking activity. We conclude that the mitochondria, activated by IGF-1R signaling, constitute a critical regulator of information processing in hippocampal neurons by maintaining evoked-to-spontaneous transmission ratio, while constraining synaptic facilitation at high frequencies. Excessive IGF-1R tone may contribute to hippocampal hyperactivity associated with Alzheimer's disease. PMID- 26804998 TI - Methylmercury affects cerebrovascular reactivity to angiotensin II and acetylcholine via Rho-kinase and nitric oxide pathways in mice. AB - AIMS: Methylmercury (MeHg) exposure results in increased risk of hypertension and cardiovascular diseases. In this study, we aimed to investigate whether the in vivo exposure of MeHg in mice affects blood pressure and basilar arterial responses to angiotensin II (Ang II) and acetylcholine (ACh), which are important modulators of cerebrovascular autoregulation. MAIN METHODS: Mice were exposed to MeHg (40ppm) in drinking water for 21days. Blood pressure was measured in conscious mice by an indirect tail-cuff method. Functional studies of the isolated arteries' response to vasoactive substances were performed using a micro organ-bath system. KEY FINDINGS: Systolic and mean blood pressures were significantly increased after 2 and 3weeks of treatment with MeHg, respectively. Ang II-induced contraction in an isolated basilar artery, which is mediated via Rho-kinase activation, was increased in MeHg-treated mice. ACh-induced relaxation, which is dependent on NO production from the endothelial cells, was decreased in MeHg-treated mice. However, alterations of vascular responses to Ang II and ACh were not observed in the isolated thoracic aorta. SIGNIFICANCE: This study demonstrated that the cerebral vasculature appears to be particularly sensitive to in vivo exposure of MeHg. Our results suggest that in vivo MeHg increases blood pressure and causes alterations in the cerebrovascular reactivity in response to Ang II and ACh through enhancement of Rho-kinase activity and inhibition of NO bioavailability, respectively. PMID- 26804997 TI - Neural Circuits Underlying Visually Evoked Escapes in Larval Zebrafish. AB - Escape behaviors deliver organisms away from imminent catastrophe. Here, we characterize behavioral responses of freely swimming larval zebrafish to looming visual stimuli simulating predators. We report that the visual system alone can recruit lateralized, rapid escape motor programs, similar to those elicited by mechanosensory modalities. Two-photon calcium imaging of retino-recipient midbrain regions isolated the optic tectum as an important center processing looming stimuli, with ensemble activity encoding the critical image size determining escape latency. Furthermore, we describe activity in retinal ganglion cell terminals and superficial inhibitory interneurons in the tectum during looming and propose a model for how temporal dynamics in tectal periventricular neurons might arise from computations between these two fundamental constituents. Finally, laser ablations of hindbrain circuitry confirmed that visual and mechanosensory modalities share the same premotor output network. We establish a circuit for the processing of aversive stimuli in the context of an innate visual behavior. PMID- 26804999 TI - ALDH2 gene polymorphism in different types of cancers and its clinical significance. AB - Aldehyde dehydrogenase 2 (ALDH2), an important mitochondrial enzyme governing ethanol metabolism, displays polymorphism in human. Recent evidence suggested that genetic polymorphism in ALDH2 gene may be significantly correlated with the susceptibility to cancer, such as colorectal cancer, esophageal cancer, and liver cancer. To investigate the correlation between ALDH2 mutant gene and the risk of a certain cancer, many studies have been done by testing the ALDH2 genotype in patients with cancers. Here, we summarized 84 ALDH2 gene single nucleotide polymorphism (SNP) sites in human cancer, which focus primarily on the rs671 SNP site. As a novel biological marker, ALDH2 displays a very attractive prospect in the screening, diagnosis and evaluation of the prognosis of many diseases. Moreover, much attention has been attracted to the studies of the biological functions and potential value of ALDH2 in the human cancer treatment. This review will provide an overview about the clinical prospects of ALDH2 based on the available information. PMID- 26805000 TI - Early beta-Amyloid-induced Synaptic Dysfunction Is Counteracted by Estrogen in Organotypic Hippocampal Cultures. AB - In the present study we set up a model of slow progression of neuronal injury by exposing organotypic hippocampal cultures to a low concentration of Amyloid beta (25-35) peptide (Abeta, 2 MUM) to analyze the time-related effects of 17-beta estradiol (17beta-E2, 10 nM). Neuronal death occurs after 7 d and is prevented by addition of 17beta-E2 24 h prior to, together with or 48 h after exposure to Abeta. This effect is mimicked by selective ERalpha agonist PPT (100 nM). Treatment with Abeta leads to early and transient (16-72 h) increase of pre- and post-synaptic proteins synaptophysin and PSD95, followed by a decrease coincident with neuronal death (7d), all prevented by 17beta-E2. At 72 h of Abeta exposure, synaptic activity is increased, as by higher levels of glutamate and increased loading and unloading of FM 1-43-labeled synaptic vesicles. All these effects are also prevented by 17beta-E2. These data point out beneficial effects of estrogen on early Abeta-induced synaptic disruption. PMID- 26805001 TI - Clockwise insertion: A risk factor of pancreatic hyperamylasemia and acute pancreatitis after peroral balloon-assisted enteroscopy. PMID- 26805002 TI - Resilience is associated with low psychological distress in renal transplant recipients. AB - OBJECTIVE: Renal transplantation (RT) is a significant life event; its subsequent challenges often lead to psychological distress, which substantially lowers patients' quality of life. The purpose of this study was to screen psychological distress and examine the relationships between resilience and psychological distress in RT recipients. METHODS: Participants were 139 RT recipients from the RT follow-up clinic and ward in the departments of nephrology of three general hospitals in Jinan, China. They were assessed using the Connor-Davidson Resilience Scale, Perceived Social Support Scale and Kessler Psychological Distress Scale. Logistic regression analyses were used to evaluate the relationships between resilience and psychological distress after adjusting for perceived social support. RESULTS: Fifty-nine (42.4%) RT recipients were considered as experiencing "psychological distress" (K10 score >= 22). Resilience was associated with psychological distress after controlling for perceived social support and sociodemographic variables: a one-point increase in resilience decreased the likelihood of having possible psychological distress (odds ratio=0.945, 95% confidence interval=0.914-0.976, P<.01). CONCLUSIONS: The present study suggests that resilience was significantly associated with low psychological distress in RT recipients. Psychosocial interventions focused on resilience might provide useful approaches to overcome psychological distress in RT recipients. PMID- 26805004 TI - Using data mining techniques to characterize participation in observational studies. AB - Data mining techniques are gaining in popularity among health researchers for an array of purposes, such as improving diagnostic accuracy, identifying high-risk patients and extracting concepts from unstructured data. In this paper, we describe how these techniques can be applied to another area in the health research domain: identifying characteristics of individuals who do and do not choose to participate in observational studies. In contrast to randomized studies where individuals have no control over their treatment assignment, participants in observational studies self-select into the treatment arm and therefore have the potential to differ in their characteristics from those who elect not to participate. These differences may explain part, or all, of the difference in the observed outcome, making it crucial to assess whether there is differential participation based on observed characteristics. As compared to traditional approaches to this assessment, data mining offers a more precise understanding of these differences. To describe and illustrate the application of data mining in this domain, we use data from a primary care-based medical home pilot programme and compare the performance of commonly used classification approaches - logistic regression, support vector machines, random forests and classification tree analysis (CTA) - in correctly classifying participants and non-participants. We find that CTA is substantially more accurate than the other models. Moreover, unlike the other models, CTA offers transparency in its computational approach, ease of interpretation via the decision rules produced and provides statistical results familiar to health researchers. Beyond their application to research, data mining techniques could help administrators to identify new candidates for participation who may most benefit from the intervention. PMID- 26805005 TI - ALA-PDT inhibits proliferation and promotes apoptosis of SCC cells through STAT3 signal pathway. AB - Previous studies suggest that apoptosis of carcinoma cells led by photodynamics is mainly intrinsic apoptosis, but whether the extrinsic pathway is involved in the treatment of carcinoma by photodynamic therapy is not confirmed. This research investigated the effect of ALA-PDT on the proliferation and apoptosis of SCC cell A431 and COLO-16, and discussed the role played by JAK/STAT3 signal pathway in this process. Our data showed that the expression levels STAT3 and p STAT3 protein in the cancer tissue are higher than the corresponding adjacent tissue to carcinoma. The expression level of p-STAT3 in cancerous tissue has a correlation with the tumor size and tissue histopathological differentiation. ALA PDT could inhibit proliferation of A431 and COLO-16 cells, STAT3 knock down could enhance ALA-PDT's inhibition of cell proliferation, and promote apoptosis induced by ALA-PDT. On the other hand, overexpression of STAT3 has the opposite effect. In addition, ALA-PDT can weaken the protein expression of STAT3 and its target gene Bcl-2 mRNA, and ALA-PDT can strengthen the protein expression of STAT3's target gene Bax mRNA. Overexpression of STAT3 can offset the effect on Bcl-2 and Bax by ALA-PDT; on the other hand, STAT3 knocking down can strengthen ALA-PDT's effect on Bcl-2 and Bax. PMID- 26805006 TI - Patients' perceptions of antimicrobial photodynamic therapy in the management of chronic periodontitis. AB - The aim of this study is to evaluate patients' perception of antimicrobial photodynamic therapy (aPDT) in the management of chronic periodontitis. 90 patients (51 females and 39 males) with untreated localized chronic periodontitis were randomly assigned to receive SRP with aPDT (test group) or SRP alone (control group) in a single-centered double-blinded randomized and controlled clinical trial. Patients' perception in terms of changes in bleeding gums, pain in gums while chewing, bad breath and sensitive gums along with pain during the procedure and patient acceptance were recorded for 6 months after treatment by a periodontist who was blinded to the procedure. Inter-group and intra-group statistical analyses were performed. Significant difference between the frequencies of two groups with respect to each variable was assessed using non parametric test. Patients' report of bleeding gums and pain in the gums while chewing showed statistically significant reduction in the test group at 2 weeks and 1 month (p<0.05). Also, a significant difference was detected at 1 month between SRP and SRP+aPDT in terms of halitosis (p<0.05). No statistically significant change was observed between two groups in terms of sensitive gums, pain during procedure and patient acceptance. Patients perceived short-term benefits of single session of aPDT therapy due to the reduction in bleeding gums, halitosis and pain while chewing following treatment. Further studies are required to assess the effectiveness of aPDT for a longer-term and following multiple sessions. PMID- 26805008 TI - Electrocardiographic Tpeak to Tend interval: The short and long of it. PMID- 26805007 TI - CoA protects against the deleterious effects of caloric overload in Drosophila. AB - We developed a Drosophila model of T2D in which high sugar (HS) feeding leads to insulin resistance. In this model, adipose TG storage is protective against fatty acid toxicity and diabetes. Initial biochemical and gene expression studies suggested that deficiency in CoA might underlie reduced TG synthesis in animals during chronic HS feeding. Focusing on the Drosophila fat body (FB), which is specialized for TG storage and lipolysis, we undertook a series of experiments to test the hypothesis that CoA could protect against the deleterious effects of caloric overload. Quantitative metabolomics revealed a reduction in substrate availability for CoA synthesis in the face of an HS diet. Further reducing CoA synthetic capacity by expressing FB-specific RNAi targeting pantothenate kinase (PK orfumble) or phosphopantothenoylcysteine synthase (PPCS) exacerbated HS-diet induced accumulation of FFAs. Dietary supplementation with pantothenic acid (vitamin B5, a precursor of CoA) was able to ameliorate HS-diet-induced FFA accumulation and hyperglycemia while increasing TG synthesis. Taken together, our data support a model where free CoA is required to support fatty acid esterification and to protect against the toxicity of HS diets. PMID- 26805009 TI - Design and functionality of a smart fentanyl iontophoretic transdermal system for the treatment of moderate-to-severe postoperative pain. AB - Fentanyl iontophoretic transdermal system (ITS) is a patient-controlled analgesia system used for the management of acute postoperative pain. The first-generation fentanyl ITS was an integrated one-piece system; however, corrosion that could limit reliability was detected in a small number of systems. A second-generation fentanyl ITS was designed to separate the hydrogels in the Drug Unit from the electronic circuit of the Controller during manufacture and storage, removing the primary cause of corrosion and thereby improving reliability. No evidence of corrosion has been observed in over 10,000 systems tested in real-time aging studies for the second generation fentanyl ITS. The second generation fentanyl ITS design features combine to ensure safe operation of the system with high reliability. PMID- 26805010 TI - Carbon monoxide protonation in condensed phases and bonding to surface superacidic Bronsted centers. AB - Using infrared (IR) spectroscopy and density functional theory (DFT) calculations, interaction of CO with the strongest known pure Bronsted carborane superacids, H(CHB11Hal11) (Hal = F, Cl), was studied. CO readily interacted at room temperature with H(CHB11F11) acid, forming a mixture of bulk salts of formyl and isoformyl cations, which were in equilibrium An(-)H(+)CO COH(+)An(-). The bonding of CO to the surface Bronsted centers of the weaker acid, H(CHB11Cl11), resulted in breaking of the bridged H-bonds of the acid polymers without proton transfer (PT) to CO. The binding occurred via the C atom (blue shift DeltanuCO up to +155-167 cm(-1), without PT) or via O atom (red shift DeltanuCO up to -110 cm( 1), without PT) always simultaneously, regardless of whether H(+) is transferred to CO. IR spectra of all species were interpreted by B3LYP/cc-pVQZ calculations of the simple models, which adequately mimic the ability of carborane acids to form LH(+)CO, LH(+)CO, COH(+)L, and COH(+)L compounds (L = bases). The CO bond in all compounds was triple. Acidic strength of the Bronsted centers of commonly used acid catalysts, even so-called superacidic catalysts, is not sufficient for the formation of the compounds studied. PMID- 26805011 TI - A novel murine model of Clostridium sordellii myonecrosis: Insights into the pathogenesis of disease. AB - Clostridium sordellii infections have been reported in women following natural childbirth and spontaneous or medically-induced abortion, injection drug users and patients with trauma. Death is rapid and mortality ranges from 70 to 100%. Clinical features include an extreme leukemoid reaction, the absence of fever, and only minimal pain or erythema at the infected site. In the current study, we developed a murine model of C. sordellii soft tissue infection to elucidate the pathogenic mechanisms. Mice received 0.5, 1.0 or 2.0 * 10(6) CFU C. sordellii (ATCC 9714 type strain) in the right thigh muscle. All doses caused fatal infection characterized by intense swelling of the infected limb but no erythema or visible perfusion deficits. Survival rates and time to death were inoculum dose-dependent. Mice developed a granulocytic leukocytosis with left shift, the onset of which directly correlated with disease severity. Histopathology of infected tissue showed widespread edema, moderate muscle damage and minimal neutrophil infiltration. Circulating levels of granulocyte colony-stimulating factor (G-CSF), soluble tumor necrosis factor receptor I (sTNF-RI) and interlukin 6 (IL-6) were significantly increased in infected animals, while TNF-alpha, and IL-1beta levels were only mildly elevated, suggesting these host factors likely mediate the leukocytosis and innate immune dysfunction characteristic of this infection. Thus, this model mimics many of the salient features of this infection in humans and has allowed us to identify novel targets for intervention. PMID- 26805012 TI - Phycocyanin prevents methylglyoxal-induced mitochondrial-dependent apoptosis in INS-1 cells by Nrf2. AB - Methylglyoxal (MG) is a reactive dicarbonyl compound, whose abnormal accumulation in diabetic patients exerts deleterious effects on cells and tissues. The beta cell is the main target cell of Type 2 diabetes, and its insulin secretion injury and cell apoptosis can be due to mitochondrial dysfunction. Previous studies have demonstrated MG induced beta-cell apoptosis. However, little is known about the effect of MG on beta-cell mitochondrial dysfunction. Phycocyanin (PC) has been demonstrated to possess various biological activities including the effects on diabetic models in vivo. The aim of this study was to determine the protective effect of PC against methylglyoxal (MG)-induced dysfunction in pancreatic beta cell INS-1 and also the mechanism. We demonstrated that MG induced mitochondrial dysfunction by the decline in ATP levels, and the increase of the level of intracellular reactive oxygen species (ROS). Furthermore, MG released cytochrome c and apoptosis-inducing factor (AIF) from the mitochondrion, induced changes in the expression of Bcl-2 family members, activated caspases and increased PARP cleavage. Interestingly, PC activated nuclear erythroid-related factor 2 (Nrf2), and Nrf2 activation as well as antioxidant enzymes HO-1 and glyoxalase 1 (Glo-1) were confirmed to be involved in the mechanisms underlying the protection of PC by RNA interference. Altogether, these results demonstrated that PC prevented mitochondrial-dependent apoptosis in MG-induced INS-1 cells and the effect was associated with Nrf2 activation. PMID- 26805013 TI - Anaphylaxis induced by proton pump inhibitors. PMID- 26805014 TI - Exercise and diet in the management of nonalcoholic fatty liver disease. AB - Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition worldwide, and is projected to become the leading cause for liver transplantation in the United States as early as 2020. The mainstay of treatment remains lifestyle modification with diet and exercise recommendations, as although some pharmacological treatments such as glitazones and Vitamin E have shown benefit, there are concerns regarding long term safety. The evidence base for dietary interventions in NAFLD such as the Mediterranean diet, omega-3 polyunsaturated fatty acids and coffee is mainly derived from observational data with questionable validity. Where trials exist, they have shown benefit for surrogate outcomes such as hepatic steatosis and insulin resistance, but no trials have been conducted with salient clinical outcomes such as reduction in progression to chronic liver disease. Benefit in surrogate outcomes has also been seen for aerobic, anaerobic and combined modality exercise but it remains unclear if one type is superior. Furthermore, a reduction in sedentary time appears equally important. To provide a sound evidence base for lifestyle recommendations to people with NAFLD, longer duration trials of standardized dietary or exercise interventions, and testing various doses, types and with liver related outcomes, are essential. PMID- 26805015 TI - Nonalcoholic fatty future disease. PMID- 26805017 TI - Botulinum neurotoxin type-A enters a non-recycling pool of synaptic vesicles. AB - Neuronal communication relies on synaptic vesicles undergoing regulated exocytosis and recycling for multiple rounds of fusion. Whether all synaptic vesicles have identical protein content has been challenged, suggesting that their recycling ability may differ greatly. Botulinum neurotoxin type-A (BoNT/A) is a highly potent neurotoxin that is internalized in synaptic vesicles at motor nerve terminals and induces flaccid paralysis. Recently, BoNT/A was also shown to undergo retrograde transport, suggesting it might enter a specific pool of synaptic vesicles with a retrograde trafficking fate. Using high-resolution microscopy techniques including electron microscopy and single molecule imaging, we found that the BoNT/A binding domain is internalized within a subset of vesicles that only partially co-localize with cholera toxin B-subunit and have markedly reduced VAMP2 immunoreactivity. Synaptic vesicles loaded with pHrodo BoNT/A-Hc exhibited a significantly reduced ability to fuse with the plasma membrane in mouse hippocampal nerve terminals when compared with pHrodo-dextran containing synaptic vesicles and pHrodo-labeled anti-GFP nanobodies bound to VAMP2-pHluorin or vGlut-pHluorin. Similar results were also obtained at the amphibian neuromuscular junction. These results reveal that BoNT/A is internalized in a subpopulation of synaptic vesicles that are not destined to recycle, highlighting the existence of significant molecular and functional heterogeneity between synaptic vesicles. PMID- 26805018 TI - Exercise intervention increases expression of bone morphogenetic proteins and prevents the progression of cartilage-subchondral bone lesions in a post traumatic rat knee model. AB - OBJECTIVE: This study aimed to determine whether treadmill walking (TW) prevents the progression of post-traumatic osteoarthritic changes in cartilage-subchondral bone unit, and whether the exercise timing changes the exercise efficacy in destabilized medial meniscus (DMM) rat knees. DESIGN: Twelve-week-old male Wistar rats underwent DMM surgery on their right knees and sham surgery on their left knees and were assigned to either the sedentary (n = 10) or walking (n = 24) groups. The rats in the walking group were subjected to TW from day 2 through 4 weeks, from 4 through 8 weeks, or from day 2 through 8 weeks (n = 8 per group). Osteoarthritic changes of cartilage and subchondral bone were assessed with micro computed tomography, histology, and immunohistochemistry 8 weeks after surgery. RESULTS: TW prevented the progression of cartilage and subchondral bone lesions induced by the DMM, and increased bone morphogenetic protein (BMP)-2 and -6 expressions in superficial zone chondrocytes and bone-lining cells including osteoblasts. Furthermore, the TW-induced increase in BMPs varied with the exercise timing. Beginning TW 4 weeks after DMM surgery was the best option for increasing BMPs, coinciding with the most robust prevention of osteoarthritic changes. CONCLUSIONS: TW increased the expression of BMPs and prevented the progression of cartilage-subchondral bone lesions in rat knees with a DMM. Selective exercise timing may be a key factor in the development of an exercise regimen for preventing the progression of post-traumatic osteoarthritis (PTOA). Furthermore, exercise may have favorable effects even after the PTOA has been developed. PMID- 26805016 TI - Hypovitaminosis D in bariatric surgery: A systematic review of observational studies. AB - BACKGROUND: Obesity is a public health problem that carries global and substantial social and economic burden. Relative to non-surgical interventions, bariatric surgery has the most substantial and lasting impact on weight loss. However, it leads to a number of nutritional deficiencies requiring long term supplementation. OBJECTIVES: The aims of this paper are to review 25 hydroxyvitamin D [25(OH)D] status pre and post bariatric surgery, describe the dose response of vitamin D supplementation, and assess the effect of the surgical procedure on 25(OH)D level following supplementation. METHODS: We searched Medline, PubMed, the Cochrane Library and EMBASE, for relevant observational studies published in English, from 2000 to April 2015. The identified references were reviewed, in duplicate and independently, by two reviewers. RESULTS: We identified 51 eligible observational studies assessing 25(OH)D status pre and/or post bariatric surgery. Mean pre-surgery 25(OH)D level was below 30ng/ml in 29 studies, and 17 of these studies showed mean 25(OH)D levels <=20ng/ml. Mean 25(OH)D levels remained below 30ng/ml following bariatric surgery, despite various vitamin D replacement regimens, with only few exceptions. The increase in post-operative 25(OH)D levels tended to parallel increments in vitamin D supplementation dose but varied widely across studies. An increase in 25(OH)D level by 9-13ng/ml was achieved when vitamin D deficiency was corrected using vitamin D replacement doses of 1100-7100IU/day, in addition to the usual maintenance equivalent daily dose of 400-2000IU (total equivalent daily dose 1500 9100IU). There was no difference in mean 25(OH)D level following supplementation between malabsorptive/combination procedures and restrictive procedures. CONCLUSION: Hypovitaminosisis D persists in obese patients undergoing bariatric surgery, despite various vitamin D supplementation regimens. Further research is needed to determine the optimal vitamin D dose to reach desirable 25(OH)D levels in this population, and to demonstrate whether this dose varies according to the surgical procedure. PMID- 26805019 TI - MicroRNA-155 suppresses autophagy in chondrocytes by modulating expression of autophagy proteins. AB - OBJECTIVE: Autophagy dysfunction has been reported in osteoarthritis (OA) cartilage. The objective of this study was to investigate the role of microRNA 155 (miR-155), which is overexpressed in OA, in the regulation of autophagy in human chondrocytes. DESIGN: Rapamycin (50 nM) and 2-deoxyglucose (2-DG) (5 mM) were used to stimulate autophagy in primary human articular chondrocytes and in the T/C28a2 human chondrocyte cell line. Cells were transfected with LNA GapmeR or mimic specific for miR-155 and autophagy flux was assessed by LC3 western blotting and by Cyto-ID((r)) dye quantification in autophagic vacuoles. Expression of predicted miR-155 targets in the autophagy pathway were analyzed by real-time PCR and western blotting. RESULTS: Autophagy flux induced by rapamycin and 2-DG was significantly increased by miR-155 LNA, and significantly decreased after miR-155 mimic transfection in T/C28a2 cells and in human primary chondrocytes. These effects of miR-155 on autophagy were related to suppression of gene and protein expression of key autophagy regulators including Ulk1, FoxO3, Atg14, Atg5, Atg3, Gabarapl1, and Map1lc3. CONCLUSION: MiR-155 is an inhibitor of autophagy in chondrocytes and contributes to the autophagy defects in OA. PMID- 26805021 TI - Comorbidity in Drivers with Parkinson's Disease. AB - OBJECTIVES: To determine the effect of comorbidity on fitness-to-drive recommendations that physicians and on-road driving assessors make and to investigate the agreement in fitness-to-drive recommendations between physicians and on-road driving assessors. DESIGN: Retrospective. SETTING: Data on comorbidities associated with Parkinson's disease (PD) and fitness-to-drive recommendations were investigated. PARTICIPANTS: Individuals with PD who underwent an official on-road test in Belgium (N = 72). MEASUREMENTS: Correlations between comorbidity and fitness-to-drive recommendations were calculated. Stepwise logistic regression models were used to investigate whether comorbidity was an independent predictor of fitness-to-drive recommendations (pass/fail) that the physicians or the on-road assessors made. The percentage of agreement and the prevalence and bias-adjusted kappa (PABAK) were used to investigate agreement between the physicians and the on-road assessors. RESULTS: Moderate correlations were found between comorbidity and fitness-to-drive recommendations that the physicians (rho = 0.34, P = .004) and the on-road assessors (rho = 0.30, P = .01) made. Comorbidity was the most important determinant (coefficient of determination = 0.16, P = .005) of the physicians fitness-to-drive recommendations. No significant effect of comorbidity on the on road recommendations was found. The physicians and the on-road assessors agreed in 46 (64%) of the cases (PABAK = 0.46, P < .001). CONCLUSION: Comorbidity plays a role in physicians' recommendations of fitness to drive that may explain, in part, inconsistencies between physicians and on-road assessors' fitness-to-drive recommendations. This study indicates the need for an interdisciplinary dialogue between physicians and on-road assessors to reach a comprehensive fitness-to drive decision. PMID- 26805020 TI - The Regulation of Exosporium-Related Genes in Bacillus thuringiensis. AB - Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis (Bt) are spore forming members of the Bacillus cereus group. Spores of B. cereus group species are encircled by exosporium, which is composed of an external hair-like nap and a paracrystalline basal layer. Despite the extensive studies on the structure of the exosporium-related proteins, little is known about the transcription and regulation of exosporium gene expression in the B. cereus group. Herein, we studied the regulation of several exosporium-related genes in Bt. A SigK consensus sequence is present upstream of genes encoding hair-like nap proteins (bclA and bclB), basal layer proteins (bxpA, bxpB, cotB, and exsY ), and inosine hydrolase (iunH). Mutation of sigK decreased the transcriptional activities of all these genes, indicating that the transcription of these genes is controlled by SigK. Furthermore, mutation of gerE decreased the transcriptional activities of bclB, bxpB, cotB, and iunH but increased the expression of bxpA, and GerE binds to the promoters of bclB, bxpB, cotB, bxpA, and iunH. These results suggest that GerE directly regulates the transcription of these genes, increasing the expression of bclB, bxpB, cotB, and iunH and decreasing that of bxpA. These findings provide insight into the exosporium assembly process at the transcriptional level. PMID- 26805023 TI - BCB Special Issue on Epigenetics. PMID- 26805024 TI - Effect of phytosanitary irradiation and methyl bromide fumigation on the physical, sensory, and microbiological quality of blueberries and sweet cherries. AB - BACKGROUND: The objective of this study was to determine whether irradiation could serve as a suitable phytosanitary treatment alternative to methyl bromide (MB) fumigation for blueberries and sweet cherry and also to determine the effect of phytosanitary irradiation treatment on survival of Salmonella spp. and Listeria monocytogenes on these fruit. 'Bluecrop' blueberries (Vaccinium corymbosum) and 'Sweetheart' cherries (Prunus avium) were irradiated at 0.4 kGy or fumigated with methyl bromide and evaluated for quality attributes during storage. RESULTS: Irradiation caused an immediate decrease in firmness of both fruit without further significant change during storage. Fumigated fruit, in contrast, softened by 11-14% during storage. Irradiation did not adversely affect blueberry and cherry shelf-life. MB fumigation did not impact blueberry and cherry quality attributes initially; however, fumigated fruit exhibited greater damage and mold growth than the control and irradiated samples during storage. Irradiation at 400 Gy resulted in a ~1 log CFU g(-1) reduction in Salmonella spp. and Listeria monocytogenes counts, indicating that this treatment cannot significantly enhance safety. CONCLUSION: This study indicates that irradiation at a target dose of 0.4 kGy for phytosanitary treatment does not negatively impact blueberry and cherry quality and can serve as an alternative to methyl bromide fumigation. (c) 2016 Society of Chemical Industry. PMID- 26805025 TI - Effects of auditory enhancement on the loudness of masker and target components. AB - Auditory enhancement refers to the observation that the salience of one spectral region (the "signal") of a broadband sound can be enhanced and can "pop out" from the remainder of the sound (the "masker") if it is preceded by the broadband sound without the signal. The present study investigated auditory enhancement as an effective change in loudness, to determine whether it reflects a change in the loudness of the signal, the masker, or both. In the first experiment, the 500-ms precursor, an inharmonic complex with logarithmically spaced components, was followed after a 50-ms gap by the 100-ms signal or masker alone, the loudness of which was compared with that of the same signal or masker presented 2 s later. In the second experiment, the loudness of the signal embedded in the masker was assessed with and without a precursor using the same method, as was the loudness of the entire signal-plus-masker complex. The results suggest that the precursor does not affect the loudness of the signal or the masker alone, but enhances the loudness of the signal in the presence of the masker, while leaving the loudness of the surrounding masker unaffected. The results are consistent with an explanation based on "adaptation of inhibition" [Viemeister and Bacon (1982). J. Acoust. Soc. Am. 71, 1502-1507]. PMID- 26805027 TI - Large-scale synthesis of hybrid metal oxides through metal redox mechanism for high-performance pseudocapacitors. AB - Electrochemical performance and production cost are the main concerns for the practical application of supercapacitors. Here we report a simple and universally applicable method to prepare hybrid metal oxides by metal redox reaction utilizing the inherent reducibility of metals and oxidbility of for the first time. As an example, Ni(OH)2/MnO2 hybrid nanosheets (NMNSs) are grown for supercapacitor application by self-reaction of Ni foam substrates in KMnO4 solution at room temperature. The obtained hybrid nanosheets exhibit high specific capacitance (2,937 F g(-1)). The assembled solid-state asymmetric pseudocapacitors possess ultrahigh energy density of 91.13 Wh kg(-1) (at the power density of 750 W kg(-1)) and extraordinary cycling stability with 92.28% capacitance retention after 25,000 cycles. Co(OH)2/MnO2 and Fe2O3/MnO2 hybrid oxides are also synthesized through this metal redox mechanism. This green and low-cost method is capable of large-scale production and one-step preparation of the electrodes, holding promise for practical application of high-performance pseudocapacitors. PMID- 26805026 TI - Aging alters bone-fat reciprocity by shifting in vivo mesenchymal precursor cell fate towards an adipogenic lineage. AB - Bone marrow derived mesenchymal progenitor cells (MPCs) play an important role in bone homeostasis. Age-related changes occur in bone resulting in a decrease in bone density and a relative increase in adipocity. Although in vitro studies suggest the existence of an age-related lineage switch between osteogenic and adipogenic fates, stem cell and microenvironmental contributions to this process have not been elucidated in vivo. In order to study the effects of MPC and microenvironmental aging on functional engraftment and lineage switching, transplantation studies were performed under non-myeloablative conditions in old recipients, with donor MPCs derived from young and old green fluorescent protein (GFP) transgenic mice. Robust engraftment by young MPCs or their progeny was observed in the marrow, bone-lining region and in the matrix of young recipients; however, significantly lower engraftment was seen at the same sites in old recipients transplanted with old MPCs. Differentiation of transplanted MPCs strongly favored adipogenesis over osteogenesis in old recipients irrespective of MPC donor age, suggesting that microenvironmental alterations that occur with in vivo aging are predominately responsible for MPC lineage switching. These data indicate that aging alters bone-fat reciprocity and differentiation of mesenchymal progenitors towards an adipogenic fate. PMID- 26805029 TI - Development of the Gay and Lesbian Relationship Satisfaction Scale. AB - This article describes the development and evaluation of the Gay and Lesbian Relationship Satisfaction Scale (GLRSS) as a measure of individuals' gay and lesbian same-gender relationship satisfaction and social support. Clinicians and researchers administer relationship satisfaction scales to persons in gay and lesbian relationships with a heteronormative assumption that scales developed and validated with opposite-gender couples measure identical relationship issues. Gay and Lesbian couples have unique concerns that influence relationship satisfaction, most notably social support. Using online recruitment and data collection, the GLRSS was evaluated with data from 275 gay and lesbian individuals in a same-gender relationship. PMID- 26805028 TI - Chinese expert consensus on the endoscopic management of foreign bodies in the upper gastrointestinal tract (2015, Shanghai, China). PMID- 26805032 TI - Impression management and achievement motivation: Investigating substantive links. AB - In this research, we investigate impression management (IM) as a substantive personality variable by linking it to differentiated achievement motivation constructs, namely achievement motives (workmastery, competitiveness, fear of failure) and achievement goals (mastery-approach, mastery-avoidance, performance approach, performance-avoidance). Study 1 revealed that IM was a positive predictor of workmastery and a negative predictor of competitiveness (with and without self-deceptive enhancement (SDE) controlled). Studies 2a and 2b revealed that IM was a positive predictor of mastery-approach goals and mastery-avoidance goals (without and, in Study 2b, with SDE controlled). These findings highlight the value of conceptualising and utilising IM as a personality variable in its own right and shed light on the nature of the achievement motive and achievement goal constructs. PMID- 26805030 TI - Evolutionary signals of selection on cognition from the great tit genome and methylome. AB - For over 50 years, the great tit (Parus major) has been a model species for research in evolutionary, ecological and behavioural research; in particular, learning and cognition have been intensively studied. Here, to provide further insight into the molecular mechanisms behind these important traits, we de novo assemble a great tit reference genome and whole-genome re-sequence another 29 individuals from across Europe. We show an overrepresentation of genes related to neuronal functions, learning and cognition in regions under positive selection, as well as increased CpG methylation in these regions. In addition, great tit neuronal non-CpG methylation patterns are very similar to those observed in mammals, suggesting a universal role in neuronal epigenetic regulation which can affect learning-, memory- and experience-induced plasticity. The high-quality great tit genome assembly will play an instrumental role in furthering the integration of ecological, evolutionary, behavioural and genomic approaches in this model species. PMID- 26805033 TI - Kinetically Selective Inhibitors of Human Carbonic Anhydrase Isozymes I, II, VII, IX, XII, and XIII. AB - To get a better understanding of the possibility of developing selective carbonic anhydrase (CA) inhibitors, interactions between 17 benzenesulphonamide ligands and 6 human CAs (full-length CA I, II, VII, and XIII and catalytic domains of CA IX and XII) were characterized using surface plasmon resonance and fluorescent based thermal shift assays. Kinetics revealed that the strongest binders had subnanomolar affinities with low dissociation rates (i.e., kd values around 1 * 10(-3) s(-1)) or were essentially irreversible. Chemodynamic analysis of the interactions highlighted an intrinsic mechanism of the CA-sulphonamide interaction kinetics and showed that slow dissociation rates were mediated by large hydrophobic contacts. The studied inhibitors demonstrated a high cross reactivity within the protein family. However, according to chemical phylogenetic analysis developed for kinetic data, several ligands were found to be selective against certain CA isozymes, indicating that it should be possible to develop selective CA inhibitors suitable for clinical use. PMID- 26805034 TI - The relationship between perceived injustice and the working alliance: a cross sectional study of patients with persistent pain attending multidisciplinary rehabilitation. AB - PURPOSE: Accumulating research suggests that perceived injustice is a risk factor for adverse recovery following painful injury. Presently, however, little is known about the processes by which perceived injustice influences rehabilitation outcomes. It is plausible that perceived injustice and associated anger impact rehabilitation outcomes by compromising the quality of the therapeutic working alliance; however, research has not previously examined the relationship between perceived injustice and the working alliance. Therefore, the present study investigated the association between perceived injustice, anger, and the working alliance. METHODS: Sixty-six patients with persistent pain following musculoskeletal injury participated in this study. All participants were enrolled in a standardized multidisciplinary rehabilitation programme. Participants completed self-report measures of perceived injustice, pain intensity, disability, anger intensity and regulation style, depressive symptoms, and a measure of the working alliance with their principal rehabilitation clinician. Each participant's principal clinician also completed the working alliance measure. RESULTS: Greater perceptions of injustice were associated with poorer client ratings of the working alliance. Results also showed that anger expression mediated the association between perceived injustice and the working alliance. CONCLUSION: Strategies to enhance the working alliance between rehabilitation professionals and clients with elevated levels of perceived injustice are needed. Implications for Rehabilitation Perceived injustice is associated with poor progress in rehabilitation programmes for people with musculoskeletal pain following injury. Perceived injustice is negatively associated with the quality of the therapeutic working alliance. Strategies to enhance the working alliance between rehabilitation professionals and clients with elevated levels of perceived injustice are needed. PMID- 26805035 TI - Electron microscopic visualization of complementary labeled DNA with platinum containing guanine derivative. AB - The object of the present report is to provide a method for a visualization of DNA in TEM by complementary labeling of cytosine with guanine derivative, which contains platinum as contrast-enhanced heavy element. The stretched single-chain DNA was obtained by modifying double-stranded DNA. The labeling method comprises the following steps: (i) stretching and adsorption of DNA on the support film of an electron microscope grid (the hydrophobic carbon film holding negative charged DNA); (ii) complementary labeling of the cytosine bases from the stretched single stranded DNA pieces on the support film with platinum containing guanine derivative to form base-specific hydrogen bond; and (iii) producing a magnified image of the base-specific labeled DNA. Stretched single-stranded DNA on a support film is obtained by a rapid elongation of DNA pieces on the surface between air and aqueous buffer solution. The attached platinum-containing guanine derivative serves as a high-dense marker and it can be discriminated from the surrounding background of support carbon film and visualized by use of conventional TEM observation at 100 kV accelerated voltage. This method allows examination of specific nucleic macromolecules through atom-by-atom analysis and it is promising way toward future DNA-sequencing or molecular diagnostics of nucleic acids by electron microscopic observation. PMID- 26805036 TI - Novel porous calcium aluminate/phosphate nanocomposites: in situ synthesis, microstructure and permeability. AB - Permeable porous nanomaterials have extensive applications in engineering fields. Here, we report a novel system of porous calcium aluminate/phosphate (CaAl-CaP) nanocomposites fabricated by pore generator free processing. The CaAl rich samples have close micropores and are not permeable. Interestingly, the CaP rich composites have a unique three-dimensional nanosieve structure with interconnected nanopores and exhibit excellent liquid permeability and adsorbability. The pore size has a narrow distribution of 200-500 nm. The CaAl nanoplatelets in the CaP rich composite have a thickness of 202 nm, a diameter of 1600 nm and an aspect ratio of 8. The porosity is from 19% to 40%. The bending strength and compressive strength are 40.3 MPa and 195 MPa, respectively. The CaP rich nanocomposite is highly permeable so that a water droplet can completely penetrate in 10 seconds (1 mm thick disk). The blue dye can be desorbed in 45 min by ultrasonic vibration. Given the nanosieve porous structure, good permeability/adsorbability and high mechanical properties, the CaP rich nanocomposite has big potential in applications for chemical engineering, biomedical engineering and energy/environmental engineering. PMID- 26805037 TI - Cucumis melo endornavirus: Genome organization, host range and co-divergence with the host. AB - A high molecular weight dsRNA was isolated from a Cucumis melo L. plant (referred to as 'CL01') of an unknown cultivar and completely sequenced. Sequence analyses showed that dsRNA is associated with an endornavirus for which a name Cucumis melo endornavirus (CmEV) is proposed. The genome of CmEV-CL01 consists of 15,078 nt, contains a single, 4939 codons-long ORF and terminates with a stretch of 10 cytosine residues. Comparisons of the putative CmEV-encoded polyprotein with available references in protein databases revealed a unique genome organization characterized by the presence of the following domains: viral helicase Superfamily 1 (Hel-1), three glucosyltransferases (doublet of putative capsular polysaccharide synthesis proteins and a putative C_28_Glycosyltransferase), and an RNA-dependent RNA polymerase (RdRp). The presence of three glycome-related domains of different origin makes the genome organization of CmEV unique among endornaviruses. Phylogenetic analyses of viral RdRp domains showed that CmEV belongs to a specific lineage within the family Endornaviridae made exclusively of plant-infecting endornaviruses. An RT-PCR based survey demonstrated high incidence of CmEV among melon germplasm accession (>87% of tested samples). Analyses of partial genome sequences of CmEV isolates from 26 different melon genotypes suggest fine-tuned virus adaptation and co-divergence with the host. Finally, results of the present study revealed that CmEV is present in plants belonging to three different genera in the family Cucurbitaceae. Such diverse host range is unreported for known endornaviruses and suggests a long history of CmEV association with cucurbits predating their speciation. PMID- 26805038 TI - Inhibition of herpes virus infection in oligodendrocyte cultured cells by valproic acid. AB - Valproic acid (VPA) is a small fatty acid used for treatment of different neurologic diseases such as epilepsy, migraines or bipolar disorders. VPA modulates different processes of cell metabolism that can lead to alterations in susceptibility of several cell types to the infection of Human Immunodeficiency Virus (HIV), Epstein-Barr virus (EBV), as well as to exert an inhibitory effect on the replication of different enveloped viruses in cultured cells. Taken these data into account and the fact that HSV-1 has been involved in some neuropathies, we have characterized the effect of VPA on this herpesvirus infection of the differentiation/maturation-inducible human oligodendrocyte cell line HOG, which resulted more susceptible to VPA inhibition of virus growth after cell differentiation. In these cells, the role of VPA in virus entry was tackled. Incubation with VPA induced a slight but reproducible inhibition in the virus particles uptake mainly observed when the drug was added in the adsorption or early upon infection. In addition, transcription and expression of viral proteins were significantly downregulated in the presence of VPA. Remarkably, when the infective viral production was assessed, VPA dramatically blocked the detection of infectious HSV-1 particles. Herein, our results indicate that VPA treatment of HOG cells significantly reduces the effect of HSV-1 infection, virus entry and productivity without affecting cellular viability. PMID- 26805039 TI - miR-142-3p inhibits cancer cell proliferation by targeting CDC25C. AB - OBJECTIVES: MicroRNAs (miRNAs) contribute to control of cell cycle progression and are frequently deregulated in cancer. The focus of this study was to determine effects of miR-142-3p on the cell cycle progression and cancer cell proliferation. MATERIALS AND METHODS: RT-qPCR was performed to determine expression of miR-142-3p in a range of cancer cell lines and in clinical cancer specimens. To further understand its role, we restored its expression in cancer cell lines by transfection with miR-142-3p mimics or inhibitors. Effects of miR 142-3p on cell cycle progression and cell proliferation were also determined. RESULTS: miR-142-3p was down-regulated in both cancer cell lines and cancer specimens. Its overexpression suppressed proliferation, whereas its depletion promoted it. In addition, miR-142-3p lead to cell cycle arrest in G2/M. Moreover, CDC25C was identified as being a target of miR-142-3p, ectopic expression of which reversed suppression of cell proliferation. CONCLUSIONS: Our observations suggest that miR-142-3p functioned as a tumor suppressor by targeting CDC25C. PMID- 26805043 TI - A critical view of monocyte subpopulations in human hypercholesterolemia. PMID- 26805047 TI - RELATIONSHIPS BETWEEN RESPONSE STABILITY AND ITEM ENDORSEMENT, SOCIAL DESIRABILITY, AND AMBIGUITY IN THE MMPI AND THE CPI. AB - Relationships between two indices of response stability and item endorsement, social desirability, and seven ambiguity indices were investigated separately within the MMPI, the unique items of the CPI, and two subpools moderate in endorsement and social desirability. Within the two original pools, zero-order correlations and multiple regression analyses revealed that only extremeness of endorsement and social desirability were substantially related to response stability; within the moderate subpools, however, indices of ambiguity-especially item length and ratings of global ambiguity, behavioral reference, and estimated stability-accounted for important degrees of variance individually as well as in combination. Reasons for the moderating effects of endorsement and social desirability are discussed, as are the implications for scale construction. PMID- 26805046 TI - Oxidative stress in follicular fluid of young women with low response compared with fertile oocyte donors. AB - The aim of this study was to determine the concentrations of oxidative stress markers, antioxidant enzymes and cytokines in the follicular fluid of young women with low response in ovarian stimulation cycles compared with high responders and fertile oocyte donors of the same age, to assess the impact of oxidative stress on ovarian reserve. The activity of follicular fluid antioxidant enzymes glutathione transferase, glutathione reductase and glutathione peroxidase was significantly lower in young women with reduced ovarian reserve compared with that in high responders and oocyte donors. Follicular fluid concentrations of oxidative stress marker malondialdehyde combined with 4-hydroxyalkenals and nitric oxide were higher in low responders than in high responders and oocyte donors. Significant differences between low responders and donors in concentrations of IL-2, IL-6, IL-8 and vascular endothelial growth factor were observed, with higher concentrations in low responders. However, IL-10 concentration was lower in low responders than in high responders and donors. No significant differences were found in follicular fluid concentrations of tumour necrosis factor alpha between the three groups. These results demonstrate that different concentrations of oxidative stress markers, oxidant enzymes and cytokines in low responders compared with high responders and oocyte donors may negatively impact ovarian response. PMID- 26805040 TI - Is gonococcal disease preventable? The importance of understanding immunity and pathogenesis in vaccine development. AB - Gonorrhea is a major, global public health problem for which there is no vaccine. The continuing emergence of antibiotic-resistant strains raises concerns that untreatable Neisseria gonorrhoeae may become widespread in the near future. Consequently, there is an urgent need for increased efforts towards the development of new anti-gonococcal therapeutics and vaccines, as well as suitable models for potential pre-clinical vaccine trials. Several current issues regarding gonorrhea are discussed herein, including the global burden of disease, the emergence of antibiotic-resistance, the status of vaccine development and, in particular, a focus on the model systems available to evaluate drug and vaccine candidates. Finally, alternative approaches to evaluate vaccine candidates are presented. Such approaches may provide valuable insights into the protective mechanisms, and correlates of protection, required to prevent gonococcal transmission, local infection and disease sequelae. PMID- 26805042 TI - The Chemical Biology of Human Metallo-beta-Lactamase Fold Proteins. AB - The alphabetabetaalpha metallo beta-lactamase (MBL) fold (MBLf) was first observed in bacterial enzymes that catalyze the hydrolysis of almost all beta lactam antibiotics, but is now known to be widely distributed. The MBL core protein fold is present in human enzymes with diverse biological roles, including cell detoxification pathways and enabling resistance to clinically important anticancer medicines. Human (h)MBLf enzymes can bind metals, including zinc and iron ions, and catalyze a range of chemically interesting reactions, including both redox (e.g., ETHE1) and hydrolytic processes (e.g., Glyoxalase II, SNM1 nucleases, and CPSF73). With a view to promoting basic research on MBLf enzymes and their medicinal targeting, here we summarize current knowledge of the mechanisms and roles of these important molecules. PMID- 26805048 TI - MARKER VARIABLE FACTOR ANALYSIS: A REGIONAL PRINCIPAL AXES SOLUTION. AB - Marker variable factor analysis is a method for obtaining an oblique simple structure in which primary axes are principal axes of homogeneous sub- sets of test variables. The method can be used as a confirmatory analysis t o evaluate the adequacy of an hypothesized factor structure, or it can be employed t o yield a superior factor structure associated with objectively chosen marker variables. The method is described and examples of its application in R and Q-type analyses are presented. PMID- 26805049 TI - A MONTE CARLO COMPARISON OF THE UNIVARIATE AND MULTIVARIATE METHODS FOR THE GROUPS BY TRIALS REPEATED MEASURES DESIGN. AB - Computer simulation techniques were used to compare the power and probability of Type I error (u) for the usual univariate, adjusted univariate, and multivariate tests. These tests were studied under the following conditions: (a) hormal distribution with equal correlations among levels of the repeated factor, (b) normal distribution with unequal correlations among levels of the repeated factor, (c) skewed distribution with equal correlations among levels of the repeated factor, and (d) skewed distributions with unequal correlations among levels of the repeated factor. The experimental design which was simulated was a groups by trials repeated measures design, where "groups" and "trials" are the generic terms for the non-repeated and repeated factors, respectively. When sampling from a normal distribution with unequal correlation among trials, the multivariate tests were generally more powerful than the univariate tests. However, when the correlations among trials were equal, the univariate tests were more powerful. The (Y level for the usual univariate test was the only one to differ significantly from nominal u (.06). Non-normality had little effect on the results, with the exception that the (Y level increased considerably in the multivariate test for the trials effect. PMID- 26805050 TI - ESTIMATING CONTENT-ACQUIESCENCE CORRELATION BY COVARIANCE STRUCTURE ANALYSIS. AB - A topic of continuing interest in the measurement area is response acquiescence. A recent study has demonstrated the feasibiliy of studying acquiescence or, more importantly, content/acquiescence correlation in the MMPI. Utilizing the components of variance approach, this study found that the variance due to acquiescence in scores on the Pt and Hg scales was small relative to content variance, but that the correlation between acquiescence and content may be substantial for the Pt scale. The present paper describes a general statistical procedure for investigating content variance, variance due to non-content characteristics of items, and the covariances of content and various item characteristics. The data from a previous paper are reanalyzed, using alternative covariance structure models. Maximum likelihood procedures which allow for a statistical test for parameters of interest are used. The results point to the significance of the content- acquiescence correlation in the Pt scale, but not in the Hy scale. The previous findings are verified statistically, and procedures which hold promise for other investigation into the properties of behavioral tests are described. PMID- 26805051 TI - SIMPLE STRUCTURE AND THE NUMBER OF FACTORS PROBLEM. AB - If the varimax criterion values. for rotations of successively greater numbers of principal axes of the image covariance matrix G are listed, they may be examined for two features: the unimodality of the distribution reflects the clarity of latent structure; and the peak value indicates the number of common factors present. The procedure is applied to nine published example problems and compared to other rules of thumb for determining the rank of a factor matrix. PMID- 26805052 TI - INDIVIDUAL DIFFERENCES IN SEMANTIC SPACE: A REPLICATION AND EXTENSION. AB - Using a rating task and a method of analysis which allows for individual differences in the use of semantic differential scales, substantial individual differences were found to emerge. In addition, the group average structure corresponded closely to that which has been found in traditional semantic differential research. These two findings replicate previous results. To test the usefulness of an individual differences approach, evaluative scores based on an individual's own evaluative dimension and evaluative scores based on the group average evaluative dimension were used to predict political preferences. Although both sets of scores were highly correlated with preferences, predictive power was not improved by the individual difference approach. PMID- 26805053 TI - A NOTE ON A LOWER BOUND TO THE LARGEST EIGENVALUE OF A COVARIANCE OR CORRELATION MATRIX. AB - Lower-bound estimates for the largest eigenvalues of covariance or correlation matrices are derived and evaluated. It is shown that among a restricted class of estimators for the largest eigenvalues, the proposed estimates are the weakest lower bounds. PMID- 26805055 TI - A ROTATIONAL PROCEDURE FOR SEPARATION OF TRAIT, METHOD AND INTERACTION FACTORS IN MULTTTRAIT-MULTIMETHOD MATRICES. PMID- 26805054 TI - STRUCTURAL REPRESENTATIONS OF NATURALISTIC DESCRIPTIONS OF PERSONALITY. AB - Using an open-ended questionnaire, each of a sample of college students was asked to describe the personalities of each of five people he or she knows well. A measure of concurrence of the most frequently used trait categories was used as input for hierarchical clustering and multidimensional scaling. The resulting trait structure was interpreted in terms of selected, independently measured properties of the traits. Different properties were found to distinguish the clusters at different levels of the hierarchical structure. These properties, from "most basic" (hierarchical level with few clusters) to "least basic" (hierarchical level with many clusters) are: a. evaluation, b. impulsive- inhibited, G. hard-soft, d. intellectual good-bad, e. active-passive, and f. domi nant-submissive. The most relevant properties for interpreting the multidimen- sional configurations are: a. evaluation, b. hard-soft, c. impulsive-inhibited, and d. introverted-extraverted. PMID- 26805056 TI - BRIEF REPORT: THE USE OF HIGHLY CORRELATED PREDICTORS IN REGRESSION ANALYSIS. AB - It is commonly believed that the multiple correlation cannot be increased appreciably by adding a predictor which is highly correlated with another predictor. This is based on the assumption that such a variable is redundant. An obvious exception occurs when the added variable is a suppressor variable, Le., it is correlated nearly zero with the criterion. A more general class of variables can be shown to exist which can bring the multiple correlation arbitrarily close to one. This emphasizes the importance of considering variables in combination rather than independently. PMID- 26805057 TI - DIFFERENTIATION OF RETARDED AND NORMAL CHILDREN THROUGH TOY-PLAY ANALYSIS. AB - An observational measurement technique f o r differentiation of organic mentally retarded and normal children was examined. Three groups of Ss-20 six-year-old retardates and 40 normal children matched with the retardates on CA or MA -were videotaped individually during an 18-minute period in which each S was free to play with any toys he chose. This period was divided usages in one of 10 predetermined categories of toy play. Discriminant function analyses were computed comparing the three possible pairs of groups. Significant differences were found between (a) retardates and normal 6-year-olds, (b) normal 6-year-olds and normal 3-year-olds, and (c) retardates and normal 3-year-olds. The Combinations category of toy play was the most important predictor in differentiating both normal groups from the retarded group. into 54 20-second intervals with two independent observers recording all toy. PMID- 26805059 TI - Rhodium-catalyzed selective CH functionalization of NNN tridentate chelating compounds via a rollover pathway. AB - Reported herein is the first example of the Rh(NHC)-catalyzed selective bis C-H alkylation of NNN tridentate chelating compounds in reaction with alkenes. The observed excellent site-selectivity can readily be explained by the postulated rollover pathway in the C-H bond activation step. The reaction is highly facile affording bis-alkylated tridentate products in high yields over a broad range of versatile heteroarene substrates and alkene reactants including ethylene gas, thus enabling its applications to be feasible in coordination and synthetic chemistry. PMID- 26805060 TI - [Four Cases of Hepatectomy for Liver Metastases of Intractable Hepatobiliary Pancreatic Cancers]. AB - The treatment of recurrences that occur after radical resection of intractable hepatobiliary pancreatic cancers such as intrahepatic cholangiocarcinoma, pancreatic carcinoma, and biliary tract carcinoma is more difficult than the treatment of primary lesions. In our institute, chest and abdominal CT examinations after radical resection of intractable hepatobiliary pancreatic cancers are performed about 3 times a year in order to evaluate for the possible emergence of small nodules in the liver. Instead of performing hepatectomy immediately after detecting small nodules, we conduct observations essentially for 3 to 6 months. Meanwhile, if the number of metastatic lesions tends to increase and absence of spread to other organs is confirmed, we decide to perform hepatectomy. In particular, when the detected nodule is solitary and larger than 1 cm, immediate hepatectomy is considered. We present the following 4 cases of hepatectomy for liver metastases after radical resection of intractable hepatobiliary pancreatic cancers: intrahepatic cholangiocarcinoma (n=1), gallbladder carcinoma (n=1), and pancreatic carcinoma (n=2). Liver metastases were detected at 3 to 17 months after radical resection of the primary lesion. Hepatectomy for the liver metastases was performed 14 to 18 months after the primary resection. Survival after hepatectomy was 22 to 45 months. The median survival was more than 25 months. By carefully selecting the indication for surgery, good results were obtained after hepatectomy even in cases of intractable cancers. PMID- 26805061 TI - [An Evaluation of Outcome of Surgical Treatment for Recurrence after Curative Pancreatectomy for Pancreatic Ductal Cancer]. AB - The aim of this study was to evaluate the outcome of surgical treatment for recurrence after curative pancreatectomy for pancreatic ductal cancer. Ten cases were enrolled, and the time from initial pancreatectomy to recurrence, location of recurrence, and outcome after surgical treatment for recurrence was evaluated. The time to recurrence was more than 1 year in 4 cases, and the locations of recurrence in these cases were the remnant pancreas and lung in 3 and 1 patients, respectively. Among these 4 cases, a second recurrence was observed in only 1 case, and survival after surgical treatment of the first recurrent site was more than 3 years in the other 3 cases. For the remaining 6 cases, the time to recurrence was less than 1 year and the recurrences were located in the abdomen but not in the remnant pancreas. A second recurrence was observed in all cases, and the survival time was less than 2 years in 4 out of 6 cases. Based on the results of this study, recurrence in the remnant pancreas and lung after curative resection for pancreatic ductal cancer could be a potential indication for surgical treatment. PMID- 26805062 TI - [A Case of Salvage Chemoradiotherapy for Regional Recurrence after Curative Esophagectomy]. AB - We report a case of regional recurrence of esophageal cancer after curative esophagectomy. The patient has experienced long-term survival after treatment with salvage chemoradiotherapy (CRT). A 69-year-old woman had received esophagectomy for advanced thoracic esophageal cancer (pathological T3N1M0, Stage III). Recurrence in the cervical regional lymph nodes was diagnosed 1 year 4 months after surgery. She was treated with salvage chemoradiotherapy consisting of 60 Gy radiation and cisplatin/5-fluorouracil. The metastatic lymph nodes disappeared(a complete response). She has been alive without recurrence for 7 years and 5 months since completing salvage CRT. Approximately 30-50% of patients develop recurrences of esophageal cancer after curative esophagectomy, and these patients rarely survive longer than a year. Therefore, it is important that we examine this rare case of long-term survival after recurrence of esophageal cancer. PMID- 26805064 TI - [A Study of Preoperative Chemotherapy with S-1 plus Cisplatin for Advanced Gastric Cancer]. AB - We studied the effects of preoperative chemotherapy with S-1 plus cisplatin for advanced gastric cancer. There were 16 patients who underwent radical surgery with neoadjuvant chemotherapy between 2000 and 2015. The indications for this were advanced gastric cancer with bulky N2 or N3 lymph nodes, or stage above T4a. Seven patients (43%) showed adverse events, all of which were tumors above Grade 3. Response evaluation showed PR in 13 cases (81%). The histopathological evaluation was Grade 0 in 8 patients (50%) and Grade 1a or above in 8 (50%). Death from recurrence within a year occurred in 4 cases, and 7 patients survived with no recurrence for over 5 years. All cases of survivors with no recurrence had a histopathological evaluation of Grade 1 or above. Three cases (75%) with recurrence and death within a year all had with Grade 0 tumors. We concluded that neoadjuvant chemotherapy with S-1 plus cisplatin was effective for advanced gastric cancer and that histopathological evaluation was invaluable for accurate prognosis. PMID- 26805063 TI - [Pre-Operative Treatment with Transcatheter Arterial Chemoembolization (TACE) and Hepatic Arterial Infusion (HAI) for Liver Metastasis from Gastric Cancer--A Case Report]. AB - The patient was an 83-year-old man who underwent distal gastrectomy for gastric cancer (T3, N1, M0, P0, M0, stage IIB) at a different hospital from ours. A metastatic lesion was detected in the liver 5 months after gastrectomy. Although chemotherapy with S-1 or bi-weekly CPT-11 was administered for 6 months, the liver tumor increased in size. The patient was referred to our hospital for treatment of the liver metastasis. Abdominal-computed tomography (CT) and magnetic resonance imaging (MRI) revealed a solitary metastatic liver tumor (9 cm in diameter: S7/S6/S8) with a hypervascular tumor stain. Transcatheter arterial chemoembolization (TACE) using degradable starch microspheres (DSM) plus mitomycin C, and hepatic arterial infusion (HAI) using high-dose 5-fluorouracil (5-FU) (6,000 mg/week), were performed 54 days before curative resection of the liver (S6+S7+S8+S5b/c). Histological findings revealed metastatic adenocarcinoma with a tumor thrombus in the posterior branch of the portal vein. The patient was treated with 2 courses of adjuvant chemotherapy with paclitaxel. No recurrence was observed 8 months after hepatectomy. This case suggests that combined treatment with TACE/HAI as a multimodal treatment might be effective in the management of hypervascular liver metastasis from gastric cancer. PMID- 26805065 TI - [S-1 plus Cisplatin Combination Therapy for Gastric Cancer with Peritoneal Dissemination]. AB - Peritoneal dissemination (PD) is the most common type of metastasis in advanced gastric cancer. The standard treatment of gastric cancer patients with PD is combination therapy with S-1 and cisplatin (SP therapy). Here, we describe the results of SP therapy for gastric cancer with PD. Sixteen gastric cancer patients with PD were treated with SP therapy as first-line chemotherapy. Second-look staging laparoscopy was performed for 10 patients who showed a good response to SP therapy. Gastrectomy was performed for 5 patients with P0CY0 and 1 case with P0CY1. The median survival time of all 16 patients was 571 days (19 months). The patients, who had surgery, had a significantly better survival time than the others (25 months vs 12.7 months). In conclusion, SP therapy is effective for gastric cancer with PD, and surgery for cases showing a good response to chemotherapy might improve the prognosis of patients with PD. PMID- 26805066 TI - [Clinical Outcomes and Prognosis of Salvage Thoracoscopic Esophagectomy after Definitive Chemoradiotherapy]. AB - We examined the treatment outcomes and survival rate of patients treated with salvage thoracoscopic esophagectomy after definitive chemoradiotherapy (dCRT). Twenty-seven patients who were indicated for salvage thoracoscopic esophagectomy after dCRT in our department were enrolled through April 2014. Eight patients had tumor regrowth after a complete response, and 19 had residual tumors. Two patients needed conversion to conventional thoracotomy. The operation time was 340 minutes (thoracic procedure: 125 minutes), and the estimated blood loss was 330 mL (thoracic procedure: 100 mL). The mean number of dissected nodes was 18. None of the patients experienced serious perioperative complications, and R0 surgery was performed in 24 patients. Postoperative complications developed in 15 patients (56%), and anastomotic leakage occurred in 11. Pneumonia developed in 3 patients, but none of the patients had tracheal necrosis or hospital mortality. The 5-year survival rate of all the patients was 40.4%, and the patient who underwent R0 surgery had a significantly better outcome than a patient with R1 or R2. Thoracoscopic esophagectomy is a safe option for salvage treatment of patients in an institution that has physicians experienced and skilled in thoracoscopic esophagectomy. However, it is always necessary to prepare for conversion to conventional thoracotomy. PMID- 26805067 TI - [A Case of Pathologically Complete Response of a Rectal Cancer after Preoperative Treatment with mFOLFOX6 and Radiation Therapy]. AB - A 60-year-old man who had bloody stools after sigmoid colonoscopy was admitted to our hospital. A digital examination and sigmoid colonoscopy showed a type 2 circular tumor at location Rb with incomplete mobility and tumor hemorrhage, and the result of a biopsy was moderately differentiated adenocarcinoma (tub2). Computed tomography and magnetic resonance imaging suggested a possibility of invasion of the primary rectal tumor to the sacrum. The clinical stage was cT4bN0M0H0P0, cStage II, which is generally not treatable by surgery. Sigmoid colostomy was performed, and a central venous port was implanted. After a preoperative treatment consisting of 3 courses of mFOLFOX6 and radiation therapy, the clinical stage changed to ycT2N0M0H0P0, ycStageI. Super-low anterior resection and covering ileostomy were performed 46 days after the preoperative treatment. A pathological examination revealed no residual cancer cells in the primary lesion and lymph node (Grade 3, pCR). The patient has been disease-free for 4 years and 9 months after the operation. PMID- 26805068 TI - [The Different Indications and Treatment Effect between Preoperative Chemotherapy and Preoperative Radiotherapy for Advanced Rectal Cancer]. AB - We evaluated the difference in effectiveness between preoperative radiotherapy (RT) and chemotherapy (C) as part of multimodal therapy for locally advanced rectal cancer. In the RT group, 43 patients were enrolled and preoperative radiotherapy was performed with 42.6 Gy for 4 weeks. In the C group, 16 patients were treated with preoperative chemotherapy consisting of mFOLFOX6/XELOX plus bevacizumab for 3 months. All 43 tumors in the RT group were located in the lower rectum. The C group was composed of 9 in the lower rectum and 7 in the middle or upper rectum. The C group was more advanced than the RT group in terms of depth of invasion, lymph node metastasis, and tumor diameter. The histological treatment response was better after RT (7 with little, 10 with a minor, 24 with a major, and 2 with a complete response) than after C (10 with little, 4 with a minor, 1 with a major, and 1 with a complete response). The tumor reduction ratio by colonography showed 36.5% after RT and 28.7% after C. CEA was reduced by 47.2% after RT and 45.2% after C. Though RT is more effective for local lesions than C, C is expected to be preferred as the local and systemic therapy for locally advanced rectal cancer with pelvic organ involvement or lateral lymph node metastases. PMID- 26805070 TI - [The Safety and Feasibility of Conversion Surgery for Initially Unresectable Pancreatic Cancer]. AB - BACKGROUND: By remarkable progress of chemotherapy for pancreatic cancer, we sometimes achieve resection of initially unresectable pancreatic cancer after chemotherapy. Otherwise, the safety and feasibility of radical pancreatic resection after chemotherapy is not still clear. In this report, we evaluated the safety and feasibility of conversion surgery for initially unresectable pancreatic cancer in our center. PATIENTS AND METHODS: Between 2009 and 2014, approximately 500 patients were diagnosed with unresectable pancreatic cancer and received chemotherapy, and after chemotherapy, 10 patients were found to have resectable tumors on computed tomography. We evaluated surgical complications using the Clavien-Dindo classification. Clinicopathological data were reviewed by using UICC, seventh edition, and the chemotherapeutic effect was measured by using Evans classification. RESULTS: The mean age of patients was 68 years, with 4 men and 6 women. The preoperative chemotherapy regimens were S-1 chemotherapy in 2 patients, gemcitabine in 5 patients, and gemcitabine plus S-1 chemotherapy in 3 patients. Nine patients underwent pancreatoduodenectomy, and 1 underwent distal pancreatosplenectomy. The mean operative time was 527.5 minutes, and the mean estimated blood loss was 875 mL. Surgery-related morbidity more than Grade 2 based on Clavien-Dindo classification occurred in 6 patients. Mortality was 0%. CONCLUSION: Our study suggests that conversion surgery for initially unresectable pancreatic cancer is safe and feasible. PMID- 26805069 TI - [Long Term Survival in a Case of Hilar Cholangiocarcinoma Treated with Chemotherapy and Surgery]. AB - A 67-year-old man with elevated hepatobiliary enzymes was referred to our hospital for further examination. Computed tomography indicated hilar cholangiocarcinoma of Bismuth type IV and revealed invasion of the right hepatic artery and the left portal vein. We diagnosed locally advanced unresectable hilar cholangiocarcinoma, and performed 5 courses of chemotherapy with gemcitabine plus S-1. After chemotherapy, the tumor was significantly reduced in size and vascular invasions were alleviated, so we decided to perform surgical resection. An extended left hepatectomy with caudate lobe and extrahepatic bile duct resection was performed. Although the intraoperative pathological examination was positive for cancer at the hepatic margins, we did not perform further bile duct resection because of the difficulty. After the surgery, we administered adjuvant chemotherapy with gemcitabine for 5 courses. Another 8 courses of gemcitabine plus S-1 therapy were given because of elevation of CA19-9. The tumor marker levels normalized, and the patient is still alive without findings of recurrence 4 years after the first treatment. Multidisciplinary treatment with chemotherapy and surgery may suggest the possibility of increasing long term survival even for patients with locally advanced unresectable cholangiocarcinoma. PMID- 26805071 TI - [Efficacy of Neoadjuvant Therapy for Borderline Resectable Pancreatic Cancer Involving the Superior Mesenteric Artery]. AB - Multidisciplinary therapy is essential in the treatment of borderline resectable pancreatic cancer involving the superior mesenteric artery (BR-SMA). We analyzed the outcomes of multidisciplinary treatment for BR-SMA and evaluated the efficacy of neoadjuvant therapy (NAT). We reviewed the clinical courses of 10 patients with BR-SMA. Seven patients were treated with preoperative neoadjuvant therapy (NAT group), and 3 patients underwent radical pancreaticoduodenectomy first (SF group). In the NAT group, the rate of R0 was 7/7 (100%), the induction rate of postoperative adjuvant chemotherapy (AC) was 6/7 (86%), and the first recurrence sites were the lung in 4 patients, and the liver and peritoneum in one patient each, respectively. In the SF group, the rate of R0 was 2/3 (67%) because of a positive pathological dissecting peripancreatic margin in 1 case. The induction rate of AC was 3/3 (100%), and the first recurrence sites were the liver in 2 patients, the peritoneum in 1, and a local site in 1. The disease free survival of the NAT group (median survival time [MST] 19.3 months) was significantly better than that of the SF group (MST 5.7 months) (log rank test, p=0.002). The median overall survival of the NAT and SF groups was 51.6 months and 19.5 months, respectively (p=0.128). An R0 resection could be performed in all cases in the NAT group. The NAT extended disease-free survival. We conclude that NAT is recommended in the treatment of BR-SMA. PMID- 26805072 TI - [The Efficacy of Neoadjuvant Chemoradiation Therapy for Borderline Resectable Pancreatic Cancer]. AB - INTRODUCTION: Surgical outcomes for locally advanced pancreatic cancer with severe vascular invasion are generally poor. The aim of this study was to evaluate whether neoadjuvant chemoradiation therapy (NACRT) could improve the survival of patients with locally advanced pancreatic cancer without distant metastasis. METHODS: Between 2010 and 2014, a total of 20 consecutive patients with locally advanced pancreatic cancer without distant metastasis were treated with NACRT. These patients included borderline resectable (BR) and unresectable (UR) pancreatic cancer patients according to the NCCN guidelines. All patients were treated with 2 courses of low-dose gemcitabine plus S-1 combination (GS) chemotherapy and 50.4 Gy of radiation therapy. Restaging was performed 4-6 weeks after completion of NACRT, and curative resection was performed if local control was achieved and distant metastasis was absent. RESULTS: Of the 20 patients, 7 (35.0%) underwent curative resection after NACRT. R0 resections were achieved in 6 patients (85.6%), and R1 resection was achieved in only 1 patient. Curative operation could not be performed in 13 patients (65.0%), because 3 patients refused surgery, 3 patients were diagnosed with dissemination on probe laparotomy or laparoscopy, and 7 patients had progressive disease with liver metastasis or dissemination on CT or MRI. Patients with a curative operation had a median disease-free survival (DFS) of 16.3 months and a median overall survival (OS) of 25.2 months. All of the patients without curative operation were treated with full-dose GS chemotherapy after NACRT. These patients had a median OS of 11.3 months. CONCLUSION: Our strategy for treating BR or UR pancreatic cancer patients seems to be effective and there might be survival benefits if curative operations can be performed after NACRT. PMID- 26805073 TI - [Evaluation of Pre-Therapeutic Ki-67 as a Predictive Marker for Histological Response to Neoadjuvant Therapy in Breast Cancer]. AB - There is controversy as to whether the proliferative marker Ki-67 is useful as a predictive marker for response to neoadjuvant therapy in breast cancer. We evaluated Ki-67 levels in pre-therapeutic breast cancer core biopsies from 52 breast cancer patients. These patients underwent anthracycline and taxane-based chemotherapy (n=48) or endocrine therapy (n=4) followed by surgery between March 2010 and February 2015. Expression of estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki-67 were examined by immunohistochemistry in the core needle biopsy specimens. Ki-67 levels were categorized into 3 groups: low (<20%), intermediate (20-50%), and high (>=50%). Pathological response rates were 29%, 15%, and 48% in the low, intermediate, and high-risk groups, respectively. In univariate analysis, pre-therapeutic high levels of Ki-67, as well as negative ER status were significantly associated with the responder group (p<0.05). However, neither Ki- 67 nor ER status were significantly associated with a response in multivariate analysis. Ki-67 appears to be a promising parameter for histological response to neoadjuvant therapy in breast cancer. PMID- 26805074 TI - [Outcome of Pulmonary Metastasectomy for Hepatocellular Carcinoma]. AB - Pulmonary metastasis of hepatocellular carcinoma (HCC) is considered a poor prognostic feature of the disease, and the utility of pulmonary resection is unclear. We evaluated clinical outcomes following pulmonary resection in 7 patients. All patients underwent video-assisted thoracic surgery (VATS). The median disease-free interval (DFI) was 14 (6-23) months. During pulmonary resection in 1 of the patients, intrahepatic recurrence was discovered and, 18 months later, this patient died of the recurrence. Of the remaining 6 patients, 2 patients developed intrahepatic recurrence and brain metastasis and died at 66 months and 10 months after pulmonary resection. Three patients are still alive and disease-free to date with a median follow-up duration of 42 (18-55) months. Of these 3 surviving patients, 2 patients had solitary pulmonary metastases and 1 patient had multiple bilateral pulmonary metastases; these patients underwent VATS once. The 7th patient underwent VATS 3 times for pulmonary metastasis and had no evidence of intrahepatic or extrahepatic recurrence. This patient died of an unrelated cause 15 months after the last pulmonary resection (47 months after the primary pulmonary resection). This study indicates that surgical resection of metachronous pulmonary metastases is associated with a favorable outcome in selected patients. PMID- 26805075 TI - [Efficacy of Sorafenib for Extrahepatic Recurrence of Hepatocellular Carcinoma after Liver Resection]. AB - Sorafenib is the first molecularly targeted drug recommended as a treatment for advanced hepatocellular carcinoma (HCC). Herein, we report the efficacy of sorafenib for extrahepatic recurrence of HCC. From September 2004 to March 2015, 47 patients who were diagnosed with recurrent HCC after liver resection were treated with sorafenib. The overall response rate was 17.5% (complete response: CR 1, partial response: PR 6, stable disease: SD 17, progressive disease: PD 13, SD beyond PD 3), and the disease control rate was 67.5%. The median time to disease progression, including extrahepatic recurrence, was significantly better than in the group with only intrahepatic metastasis (p=0.034). Therefore, sorafenib might be an effective treatment for extrahepatic recurrence of HCC. PMID- 26805076 TI - [Resection of Initially Unresectable Gallbladder Cancer with Multiple Liver Metastases after Chemotherapy with Gemcitabine plus Cisplatin]. AB - A 61-year-old woman was referred to our hospital for surgery for gallstones. She was diagnosed as having gallbladder cancer after a detailed radiologic examination. At the first laparotomy, gallbladder cancer with bulky invasion to the liver and multiple liver metastases were observed. Gemcitabine plus cisplatin (GC) administration was chosen. After 7 administration of GC, we changed GC to gemcitabine alone due to blood toxicity. After 7 months of chemotherapy, although CT findings showed regression of the liver invasion and the liver metastases, the serum CA19-9 level gradually increased. Because there were no obvious distant metastases on detailed radiologic examination, we performed surgery for the primary lesion after obtaining informed consent. Pathological examination demonstrated fibrosis without viable cancer cells in the metastatic liver tumor. Gemcitabine was administered as post-operative adjuvant chemotherapy. Twelve months after surgery, there was no sign of recurrence. PMID- 26805077 TI - [Usefulness of Local Therapy in Elderly Breast Cancer Patients with Distant Metastases]. AB - We investigated the usefulness of local therapy in elderly breast cancer patients with distant metastases. Sixty-four elderly breast cancer patients were encountered during 10 years. Fifty-one patients had complications. The proportion of endocrine receptor-positive tumors was 95.2%. Patients who had metastases at the first visit represented 22.6% of the study group. Advanced-stage cancers were recognized in elderly patients than other patients. The mean observation time for all the patients was 7.4 years. The mortality from cancer was 6.5%, and the mortality from other diseases was 58.1%. We divided the patients into 2 groups, the non-metastases group (group A, n=48), and the metastases group (group B, n=14). There were no significant differences between groups A and B in the rates of endocrine receptor-positive tumors, surgery rate, and survival rate. These results suggest that endocrine therapy without surgery should be considered in elderly breast cancer patients with endocrine receptor-positive tumors. PMID- 26805078 TI - [Examination of the Cases Given Primary Tumor Resection after Systemic Therapy for Metastatic Breast Cancer]. AB - We examined the records of patients with stage IV breast cancer who underwent primary tumor resection after systemic therapy. In our department, in 2013, there were 8 such cases. The average local tumor diameter was 59 mm. There was 1 case of metastases to the liver, 2 cases to the lung, 3 cases to the bone, and 1 case to the kidney. Three cases had lymph node metastases. Two cases were treated with hormonal therapy, and 6 cases received chemotherapy as preoperative systemic therapy. All cases underwent Bt plus Ax. Approximately 2 years after the surgery, 5 of the 8 patients were alive. The postoperative local control was good and we were able to continue systemic treatment for the distant metastases in all cases. We think that resection of the primary tumor improved the quality of life of the patients. However, for 1 fatal case, a brain metastasis was detected shortly after surgery. Therefore, we need to consider the patient's condition carefully before we operate. PMID- 26805079 TI - [A Case of Locally-Advanced Breast Cancer with Liver Metastasis, Treated with Mastectomy of the Primary Tumor after Chemotherapy]. AB - The patient was a 39-year-old woman who was referred to our hospital with suspicion of locally-advanced breast cancer. After several tests, she received a diagnosis of cT4bN1M1 (liver), Stage IVbreast cancer. The liver metastasis was located in S4, and was 1 cm in size. Core needle biopsy was performed on the breast tumor; the pathological diagnosis was invasive ductal carcinoma (scirrhous carcinoma), nuclear Grade (NG) 3, and HER2-positive. She received epirubicin plus cyclophosphamide (EC) followed by docetaxel (DOC) plus pertuzumab (PER) plus trastuzumab (HER). After chemotherapy, the liver metastasis and axillary lymph node metastases had disappeared on imaging findings, showing a complete response (CR), but the primary breast tumor remained, showing a partial response (PR). She underwent mastectomy and axillary lymph node dissection for local control. After surgery, no metastases including liver metastases were seen on CT. The patient is currently receiving tamoxifen and anti-HER2 therapy. PMID- 26805080 TI - [Examination of Resection for Pulmonary Tumors after Breast Cancer Surgery]. AB - There are many arguments about whether surgical resection or drug therapy is better for pulmonary metastasis after breast cancer surgery. Here, we examine 9 cases of resection for pulmonary tumors suspected of being metastases from breast cancer, at our institution. The preoperative diagnosis was difficult, with nodules less than 20 mm in all cases. Of the 9 cases, 2 cases were primary lung cancer, 4 cases were metastatic pulmonary tumors, 1 case was comorbid with lung cancer and metastatic pulmonary tumors, and 2 cases were benign pulmonary tumors. The median disease-free interval (DFI) was 6.1 (1.3-8.9) years, and the median survival time was 12.5 (2.3-17.8) years after metastasectomy. There were no changes in the hormone receptors or HER2 status between primary breast tumors and metastases. Both cases of primary lung cancer were Stage IA, and they were treated with radical resection. The 2 benign pulmonary tumors did not receive any unnecessary additional treatment. If a difficult-to-diagnose pulmonary tumor occurs after an operation for breast cancer, a pneumonectomy should be considered, not only for diagnosis but also for treatment. PMID- 26805081 TI - [Perioperative Steroid Administration for Colorectal Cancer with Synchronous Unresectable Hepatic Metastases]. AB - PURPOSE: In our institution, steroids are administered before resection of primary colorectal cancer lesions with synchronous unresectable hepatic metastases in order to avoid severe postoperative complications and hepatic failure. We herein report the results of the treatment. PATIENTS AND METHODS: Thirty-eight colorectal cancer patients with synchronous unresectable hepatic metastases were divided into 2 groups: Group S (patients who received steroids in the perioperative period) and Group N (other patients). The clinicopathological features, post-operative course, and survival were compared between the 2 groups. Hydrocortisone sodium succinate was administered twice a day from immediately before laparotomy until the second postoperative day. RESULTS: The number of patients with severe hepatic metastases and extra-hepatic metastases was significantly higher in Group S. No significant differences were observed between the 2 groups regarding the incidence of severe postoperative complications or the overall survival. Among 25 patients with liver dysfunction, the complication rate was significantly lower and survival was significantly longer in Group S compared to Group N. CONCLUSIONS: The perioperative administration of steroids to colorectal cancer patients with synchronous unresectable hepatic metastases may reduce the complication rate and may thus improve survival, especially in patients with liver dysfunction. PMID- 26805082 TI - [Two Cases of Effective Hepatic Arterial Infusion Chemotherapy for Liver Metastases of Colon Cancer Resistant to Systemic Chemotherapy]. AB - A 69-year-old man underwent right hemicolectomy for ascending colon cancer with liver metastases. Postoperative systemic chemotherapy did not reduce the metastases, and therefore, hepatic arterial infusion chemotherapy (HAI) was administered. The metastases decreased in size after 26 rounds of therapy, and the patient underwent resection. He is recurrence-free 63 months after the primary operation. A 57-year-old man underwent Hartmann's operation for sigmoid colon cancer with liver metastases. He underwent hepatic left lobe resection after metastases reduction by systemic chemotherapy. However, multiple liver metastases were detected 2 months later. Because the disease progressed despite the administration of systemic chemotherapy, HAI was utilized instead. The metastases decreased in size remarkably, and resection was performed. The patient is surviving 52 months after the primary operation while being continuously treated with HAI, resection, and systemic chemotherapy for re-recurrence. HAI is a potential alternative treatment for patients with colorectal liver metastases resistant to systemic chemotherapy. PMID- 26805083 TI - [The Significance of Primary Tumor Resection in Unresectable Stage IV Colorectal Cancer]. AB - The significance of primary tumor resection for unresectable Stage IVcolorectal cancer is controversial. In the present study, we examined cases of unresectable Stage IV colorectal cancer treated in our department. The subjects were 78 patients with unresectable Stage IV colorectal cancer who received either resection of the primary tumor, intensive chemotherapy, or both, between 2006 and 2012. The patients were divided into 2 groups: the group that received primary tumor resection (67 patients) and the non-resection group (11 patients). No differences were noted between a history of primary tumor resection and various clinicopathological factors, but the prognoses in the primary tumor resection group were favorable. The subjects were divided into 3 groups based on the selection of primary tumor resection and chemotherapy. The median survival time was 21.6 months, 11.8 months, and 8.1 months for patients who underwent chemotherapy after primary tumor resection (52 patients), patients who received primary tumor resection only (15 patients), and patients who received only chemotherapy (11 patients), respectively. The prognoses of patients who received primary tumor resection were favorable in comparison with those who received only chemotherapy. The results of the present study suggest the possibility that primary tumor resection can improve the prognoses of patients who have unresectable Stage IV colorectal cancer. PMID- 26805084 TI - [The Implications of Primary Tumor Resection during Recent Chemotherapy of Unresectable Colon Cancer]. AB - Some patients with unresectable colorectal cancer can be treated by chemotherapy leaving the primary tumor unresected, but indications and implications of a later resection of the primary tumor (RPT) are often controversial. We investigated 5 patients whose primary tumors were resected during chemotherapy, either panitumumab or bevacizumab. The median age of these patients was 63 years and all were men. The unresectable disease was liver metastases in 4 patients and a primary tumor in 2 patients. A diverting stoma was constructed before initiation of chemotherapy in 2 patients. The median interval until RPT was 8.3 months and the reasons for resection were the appearance of obstructive symptoms in 3 patients and a desire for stoma closure in 2 patients. The size of the primary tumor had decreased until RPT in all patients. RPT was performed successfully in all patients, but 2 of the 3 operations that were initiated laparoscopically had to be converted to open surgery. Intensive chemotherapy was resumed in all patients and median survival after RPT was 19 months, including a patient whose liver metastasis was also resected later. RPT can relieve obstructive symptoms and close stomas. Because intensive chemotherapy is still possible and a lengthy survival can be expected after RPT, it should be considered not merely as a palliative option but also as a treatment strategy. PMID- 26805085 TI - [Oophorectomy for Ovarian Metastasis Occurring during Chemotherapy in Gastric Cancer Patients with Peritoneal Dissemination--Report of Three Cases]. AB - We report 3 cases of advanced gastric cancer with peritoneal dissemination (PD) who underwent oophorectomy for ovarian metastases that occurred during chemotherapy. Case 1: The patient was a 43-year-old woman who had type 4 advanced gastric cancer with PD. After 24 courses of S-1 plus IV and IP paclitaxel (PTX) combination therapy, oophorectomy was performed for a rapidly growing left ovarian metastasis. Thirty-four months after the start of therapy, she has completed 44 courses of S-1 plus IV and IP PTX therapy and she is continuing the treatment. Case 2: The patient was a 77-year-old woman who underwent total gastrectomy with D2-#10 lymph node dissection and cholecystectomy for gastric cancer with PD. Right ovarian resection was performed for an ovarian metastasis 30 months after gastrectomy. She continues receiving chemotherapy 8 months after oophorectomy. Case 3: The patient was a 42-year-old woman who received S-1 plus CDDP combination therapy and 22 courses of S-1 plus IV and IP PTX for gastric cancer with PD, and oophorectomy for bilateral ovarian metastases was performed. After 10 courses of S-1 plus IV and IP PTX therapy, she died of cancer. We discuss the significance of oophorectomy during chemotherapy for advanced gastric cancer with PD. PMID- 26805086 TI - [Examination of the Usefulness of Laparoscopic Resection for Primary Lesions of Stage IV Colorectal Cancer]. AB - For patients with Stage IV colorectal cancer, primary site resection improves survival and relieves symptoms of bleeding and obstruction by the primary lesion. Laparoscopic surgery is thought to be useful for Stage IV colorectal cancer because of its low aggressiveness and the short recovery time. We examined the usefulness of laparoscopic resection of primary lesions for Stage IV colon cancer patients. Forty-one cases of Stage IV colorectal cancer treated by resection of the primary lesion were investigated, and we compared the group of patients with laparoscopic surgery (LAC) to the group of patients with open laparotomy (OP). The LAC Group was superior to the OP Group from the viewpoint of blood loss, days of hospitalization, and length of time from operation to start of chemotherapy. For Stage IV colorectal cancer, laparoscopic resection of the primary lesion is thought to be a useful method to reduce the invasiveness of treatment. PMID- 26805087 TI - [An Analysis of Placement of a Self-Expanding Metallic Stent as Bridge to Surgery for Surgical Resection of StageIV Obstructive Colorectal Cancers]. AB - In our institution, placement of a self-expanding metallic stent (SEMS) for obstructive colorectal cancer to avoid emergency operations, namely as a bridge to surgery (BTS), was introduced in April 2012. Here, we assess the efficacy and safety of pre-operative SEMS placement for treatment of Stage IV obstructive colorectal cancer. We analyzed a total of 44 cases of Stage IV colorectal cancer, which consisted of 13 obstructive cases that were surgically resected following SEMS placement as BTS (BTS group), and 31 cases that were resected in elective operations without pre-operative SEMS placement (Ope group), from April 2012 to August 2014. None of the patients had any adverse events during the SEMS procedure or after SEMS placement, and all patients of BTS group could undergo the planned operations after sufficient decompression. In the postoperative period, 1 patient of BTS group (7.7%) had anastomosis bleeding, but no other complications, including anastomosis leakage, were observed in BTS group. However more progressive primary tumors were resected in BTS group (p=0.0115), there were no significant differences for post-operative course between the 2 groups; this indicated avoiding high-risk emergency operations contributed to adequate short term outcomes in BTS group comparable to those in Ope group. SEMS placement as BTS could be performed safely for Stage IV obstructive colorectal cancer cases, and was 1 of the effective strategies for local treatment. PMID- 26805088 TI - [Examination of the Usefulness of Palliative Self-Expanding Metallic Stents in Patients with Malignant Colorectal Obstruction]. AB - Self-expanding metallic stents (SEMS) are a useful palliative option in malignant colorectal obstruction. The aim of this study was to evaluate the clinical outcomes of SEMS used for palliation. Patients with malignant colorectal obstruction who underwent SEMS insertion in our hospital from April 2014 to March 2015 were enrolled in the study. Clinical outcomes and complications of palliative SEMS insertion were retrospectively analyzed. Nine patients were enrolled in the palliative SEMS group. The success rate was 100%, while the complication rate was 11%. Successful SEMS insertion may enable oral intake in a few days, but 3 patients required up to several weeks to resume oral intake. Palliative SEMS are effective and beneficial for malignant colorectal obstruction. PMID- 26805089 TI - [Analysis of Palliative Stent Placement for Acute Malignant Colorectal Obstruction]. AB - INTRODUCTION: Recently, endoscopic placement of self-expanding-metal stents (SEMS) has been widely performed for treatment of acute malignant colorectal obstruction. This study aimed to compare the efficacy of SEMS placement as palliative treatment with that of surgical treatment in patients presenting with acute malignant colorectal obstruction. MATERIALS AND METHODS: A retrospective review was performed for 20 patients with unresectable malignant colorectal obstruction who had received insertion of SEMS (n=9) or surgical treatment (n=11) for palliation between July 2006 and M ay 2014. RESULTS: Patients who had received SEMS were in poorer clinical condition regarding age and performance status. Duration of treatment was significantly lesser and the postoperative date of initial oral intake after intervention was statistically earlier in the SEMS group. SEMS-related morbidity was found in only 2 cases of obstruction due to tumor ingrowth; these patients were successfully treated by reinsertion of SEMS. The prognosis of both groups showed no statistical difference. CONCLUSION: Palliative SEMS placement for unresectable colorectal malignant obstruction in patients with more severe clinical condition relieved obstruction without severe morbidity. Palliative SEMS placement could be an alternative to surgery for the treatment of acute unresectable colorectal obstruction. PMID- 26805091 TI - [Efficacy of Radiation Therapy for Esophageal Cancer with Bone Metastases]. AB - We retrospectively considered the validity of radiotherapy for patients with bone metastases from esophageal cancer. Eight patients have received radiotherapy in our hospital since 2007. The median age of the patients was 63 years, with 5 men and 3 women. Bone metastatic sites were 4 to the vertebrae, 3 to the ribs, 3 to the femur and 1 each to the humerus, ulna, and radius, respectively. All of the patients had other unresectable sites of metastasis. Radiotherapy reduced pain of 3 patients of PS 1 clearly. Median survival time from the start of radiation therapy was 50 days. When PS was relatively good, the possibility of easing pain and improving QOL was suggested by our data. There is a possibility that radiation therapy for patients with bone metastases from esophageal cancer can improve the QOL and alleviate pain. PMID- 26805090 TI - [Clinical Analysis of Esophageal Bypass Surgery with Nutritional Assessment in Patients with Unresectable Esophageal Cancer]. AB - BACKGROUND: Esophageal bypass surgery is palliative surgery for unresectable esophageal cancer with esophageal stenosis, which often leads to poor nutrition. We investigated the clinical characteristics, nutritional status, and outcomes of patients who underwent esophageal bypass surgery. PATIENTS AND METHODS: We reviewed 11 cases of esophageal bypass surgery for unresectable esophageal cancer performed in our hospital between 1992 and 2015, and we examined the surgical outcome along with preoperative nutritional assessment. RESULTS: There were 1, 9, and 1 cases of cStage III, IVa, and IVb, respectively. For the bypass, a gastric tube was used in 8 cases and colon reconstruction in 3. Postoperative complications were 1 case of recurrent laryngeal nerve palsy (9%), 4 cases of anastomotic leakage (36%), and 4 cases of pneumonia (36%). The preoperative nutritional status (total protein, albumin, and cholinesterase levels) in the esophageal bypass group (n=11) was significantly worse than that in the esophagectomy group (n=40). The median survival of all patients (n=11) was 5.7 months. Patients receiving induction chemoradiotherapy followed by bypass surgery (n=7) had a median survival of 15.2 months. CONCLUSION: Since patients undergoing esophageal bypass surgery often present with malnutrition, attention to anastomotic leakage and infectious complications is necessary. PMID- 26805092 TI - [Peritoneovenous Shunting as a Palliative Therapy for Refractory Ascites after Biliary Cancer Surgery]. AB - The quality of life of patients with recurrence of biliary cancer is remarkably diminished by the occurrence of refractory ascites caused by peritoneal dissemination or portal vein obstruction. In this study, we examined the effectiveness of peritoneovenous shunting (PVS) in patients with refractory ascites after recurrence of biliary cancer. PVS was performed 7 times in 5 patients, with 6 shunts (85.7%) placed from the left-side abdomen to the left subclavian vein. During the median observation period of 136 days, the ascites and symptoms of abdominal distension disappeared in 4 patients. Severe complications consisting of shunt obstruction in 2 patients and post-shunt coagulopathy in 1 patient were also observed. PVS is a useful palliative therapy for refractory ascites in patients with recurrence of biliary cancer. In patients after cancer resection, an appropriate choice of a safe placement route is critical for avoiding abdominal organ injury. The feasibility of PVS in patients with refractory ascites should be considered carefully and in context of their prognosis and performance status because severe complications may occur after this procedure. PMID- 26805093 TI - [Appropriate Biliary Drainage Methods for Unresectable Cholangiocarcinomas]. AB - We investigated the efficacy of different biliary drainage methods for the treatment of unresectable cholangiocarcinomas. We performed a retrospective study of 28 patients with unresectable cholangiocarcinomas who underwent biliary drainage at our hospital between January 2008 and June 2014 to compare the incidence of post-drainage stent dysfunction (SD) and reintervention (RI) for SD according to primary drainage method, lesion site, and complication status (the presence or absence of cholangitis). The duration of stent patency was compared between the different stent types. No significant differences in the incidence of SD and RI were found according to primary drainage methods, lesion site, or the presence or absence of cholangitis. The mean durations of stent patency for plastic and metal stents were 2.7 months and 7.4 months, respectively, suggesting that metal stents should be selected when the estimated prognosis is >=2 months. Furthermore, metal stent placement, rather than the additional placement of plastic stents, should be considered a feasible option in cases of SD. PMID- 26805094 TI - [Percutaneous Transhepatic Cholangiodrainage to Alleviate Symptoms of Afferent Loop Obstruction--A Case Report]. AB - The patient, a 78-year-old man, had undergone distal gastrectomy for a gastric ulcer 35 years previously. As melena was observed, he was referred to our department, and was subsequently diagnosed with residual gastric cancer and ascending colon cancer. Peritoneal metastasis of gastric cancer was found, and palliative surgeries, including right hemicolectomy, total gastrectomy, and Roux en-Y reconstruction were performed. Although postoperative chemotherapy was commenced, side effects led to a decreased performance status (PS), which resulted in the patient shifting to the best supportive care (BSC). Five months after surgery, the patient was urgently transferred to the hospital with upper abdominal pain, and underwent computed tomography (CT) scan. The patient was diagnosed with acute afferent loop obstruction due to peritoneal metastases. It was not possible to perform endoscopic drainage because of the stenosis; therefore, percutaneous transhepatic cholangiodrainage (PTCD) was performed to reduce the pressure in the duodenal afferent loop. Herein, we report on a case of afferent loop obstruction, for which we performed decompression of the afferent loop with PTCD, allowing the patient to continue BSC for approximately 3 months. PMID- 26805095 TI - [Usefulness of Palliative Gastrojejunal Bypass Surgery]. AB - OBJECTIVES: The aim of this study was to evaluate the usefulness of gastrojejunal bypass surgery performed in patients presenting with upper gastrointestinal tract obstruction due to unresectable advanced cancer. SUBJECTS AND METHODS: The subjects were 21 patients who underwent gastrojejunal bypass surgery at our division between 2010 and 2014 for symptom palliation. We retrospectively evaluated the operative outcomes, whether chemotherapy was administered, the oral ingestion period, and survival time. RESULTS: The median postoperative day of starting oral ingestion was 6 (range: 2-42), and the median period from decreased oral ingestion to death was 4 (range: 0-26) days. Twelve patients (57%) were discharged. Postoperative chemotherapy was prescribed to all the 9 patients who desired treatment. The median duration of oral digestion time was 61 days, and the median overall survival time was 92 days. CONCLUSION: Gastrojejunal bypass surgery is found to have the potential to not only make relatively long-term oral ingestion possible, but also broaden available treatment options, such as home care or chemotherapy, thereby contributing to improved quality of life. PMID- 26805096 TI - [Basic Studies on Locoregional Injection of a Newly Designed Chitin Sol]. AB - BACKGROUND: Systemic chemotherapy in advanced cancer cases often provokes serious adverse events. PURPOSE: We aimed to examine the fundamental properties and efficacy of a novel chitin sol, an anti-cancer agent with minor side effects designed to avoid the adverse effects of chemotherapy and enhance the QOL and ADL of patients. METHODS: DAC-70 was used to create the novel agent termed DAC-70 sol. The anti-proliferative activity was assayed by the WST method using different types of cell lines. The anti-cancer efficacy of the novel agent was examined using cancer-bearing mice. RESULTS: DAC-70 sol was easily injectable through a 21-G needle. The sol suppressed proliferation of the cells in vitro. Intra-tumor injection of DAC-70 sol inhibited the rapid growth of solid tumors in the mice. CDDP-loaded DAC-70 sol, CDDP/DAC-70 sol, successfully controlled malignant ascites in the mice (p<0.05). Neither recurrence nor severe complications were encountered in these animals. DISCUSSION: These basic data strongly suggest that locoregional administration of our newly designed DAC-70 sol and CDDP/DAC-70 sol is clinically useful as novel cancer chemotherapy for advanced cases. This warrants further clinical studies in cancer chemotherapy. PMID- 26805097 TI - [Clinical Value of "iEat(r)" in Terminal Cancer Patients Who Have Difficulty with Oral Intake of a Solid Diet]. AB - The usefulness of "iEatR" was explored in a study of 13 terminal cancer patients who had difficulty ingesting a solid diet, but could ingest a liquid diet. The patients were given a questionnaire on the flavor, appearance, and ease of consumption after sampling 2 kinds of "iEatR". Patients wishing to continue consuming this diet were able to purchase "iEatR" at their own expense and were then surveyed regarding their ongoing consumption of "iEatR". The types of cancers were esophageal in 3 patients, gastric in 7, and pancreatic in 3. In the questionnaire, 10 of the 13 patients rated the flavor as good and 12 rated the appearance and ease of eating as good. Eleven of the 13 patients purchased "iEatR", and 61.5% of patients were still consuming "iEatR" at least 2 times per week 2 weeks after the sampling. No change in the Common Terminology Criteria for Adverse Events grade was seen in any of the patients."iEatR", which emphasizes appearance and taste, is associated with improved satisfaction in terminal cancer patients who have difficulty ingesting solids, suggesting it is useful as a diet for these patients. PMID- 26805099 TI - [A Case of a Patient with Distal Bile Duct Carcinoma Who Underwent Surgical Resection Three Times for Pulmonary Metastases]. AB - A 63-year-old woman attended our hospital after diagnosis of a solitary pulmonary metastasis from a distal bile duct carcinoma. She had undergone a subtotal stomach-preserving pancreaticoduodenectomy 1 year 9 months prior to the current presentation. She was treated with right thoracoscopic pulmonary partial resection. The specimen was a solitary nodule 5 mm in diameter. In addition, she was treated with adjuvant chemotherapy involving GEM for 6 months. One year 5 months later, she was diagnosed with a second pulmonary metastasis and was treated with a left thoracoscopic partial resection. Four months later, she experienced recurrence in the right lung stump and was treated with right thoracoscopic partial resection. The specimen was a solitary nodule 21 mm in diameter. Cytopathologic examination of the pleural fluid resulted in a diagnosis of Class V. She was treated with adjuvant chemotherapy involving TS-1 for 6 months. Seven months later, she was experienced recurrence with multiple pulmonary metastases and an affected hilar lymph node. GEM/CDDP chemotherapy was started, but bone multiple metastases developed. After she received 30 Gy of radiotherapy, her pain improved. She died of cancer 5 years and 4 months after her initial pancreaticoduodenectomy, which was 3 years and 4 months after her initial pulmonary resection. We identified 14 other case reports of long-term survivors of distal bile duct carcinoma. PMID- 26805098 TI - [Survival after Sorafenib Treatment for Advanced Recurrent Hepatocellular Carcinoma with Tumor Thrombus in the Inferior Vena Cava]. AB - A 72-year-old man with chronic viral hepatitis type B undergoing surgery for hepatocellular carcinoma was found to have a recurrent tumor in the left liver with peritoneal dissemination near the inferior vena cava(IVC)and tumor thrombus in the IVC. For this patient diagnosed with Barcelona clinic liver cancer (BCLC) classification stage C hepatocellular carcinoma, we initiated 800 mg/body sorafenib. Two weeks after the initiation of sorafenib, the patient experienced grade 3 hand-foot syndrome, after which, the dose of sorafenib was reduced to 400 mg/body. After 1 year, CT showed an enlarged tumor in the left liver and multiple metastases to the lung. However, no remarkable difference was observed in the peritoneal dissemination and the tumor thrombus. He has been receiving sorafenib for 19 months with a good quality of life. Sorafenib can be provided on an outpatient basis and it may facilitate long-term survival for patients with advanced recurrent hepatocellular carcinoma with IVC tumor thrombus. This clinical condition is very rare, and the standard treatment for it still has not been established. PMID- 26805100 TI - [A Patient with Three-Year Relapse-Free Survival after Surgical Resection for Lung and Liver Metastases of Cholangiocarcinoma]. AB - We report of a patient with 3-year relapse-free survival after surgical resection for lung and liver metastases of distal cholangiocarcinoma (DCC). A quinquagenarianman was taken to a local hospital in October 2009 for yellow urine. He was diagnosed with DCC and was referred to our hospital for surgery. Pancreaticoduodenectomy was performed, and there was no residual tumor on histological examination. He did not receive any adjuvant therapy. One year 7 months after surgery, an isolated lung metastasis was identified on CT and was surgically removed. Six months after resection of the lung metastasis, a solitary liver metastasis was detected. Although systematic chemotherapy (gemcitabine plus S-1; 2 weeks treatment, 1 week drug free) was administered, the treatment was abandoned because of grade 3 (CTCAE v4.0) of skin disorders during the third course. Partial resection of the liver was performed in April 2012. Alternate-day treatment with S-1 was performed after resection of liver metastasis and is ongoing without adverse events. He has survived for more than 3 years without recurrence after liver resection. In this case of DCC metastasis, prognosis improved with surgical resection. PMID- 26805101 TI - [A Case of Local Recurrence of Bile Duct Cancer Completely Responding to Chemoradiotherapy with S-1]. AB - An 80-year-old man with common bile duct cancer was treated by pancreaticoduodenectomy with D2 lymph node dissection in October 2005. The patient presented with frequent episodes of bloody-mucous rectal discharge in July 2009. An abdominal CT demonstrated local recurrence at the hepatoduodenal ligament. We treated him with concurrent chemoradiotherapy (CRT) with single-dose S-1 chemotherapy. After 6 months, we diagnosed a complete response (CR) by follow up CT. The patient was treated with S-1 for 3 years after the diagnosis of a CR. He is alive without disease 6 years after the diagnosis of the recurrence. Concurrent CRT with S-1 chemotherapy may be the therapy of choice for recurrence of bile duct cancer. PMID- 26805102 TI - [A Case of Resected Lymph Node Recurrence of Cancer of the Papilla of Vater]. AB - We report the successful resection of lymph node recurrence of cancer of the papilla of Vater after pancreatoduodenectomy (PD). A 67-year-old man had undergone PD for adenocarcinoma of the papilla of Vater, and histopathological examination revealed well differentiated papillotubular adenocarcinoma, ly1, v0, T1, n (0), pStage IB. One year after surgery, abdominal computed tomography revealed a mass at the left side of the residual inferior pancreaticoduodenal artery (IPDA). We resected the mass, which was diagnosed as lymph node recurrence of cancer of the papilla of Vater. The patient remains alive without any evidence of recurrence 5 years since the second operation. We suggest that complete resection of lymph node surrounding the IPDA is an important surgical procedure for cancer of the papilla of Vater. There still is only limited experience with resection for recurrence of cancer of the papilla of Vater, but our case shows that it may provide for long-term survival from recurrence of cancer of the papilla of Vater. PMID- 26805103 TI - [A Case of Gemcitabine Refractory Lung Metastasis after Distal Pancreatectomy for Pancreatic Cancer, Effectively Treated with S -1 as Second Line Chemotherapy]. AB - A 64-year-old man was diagnosed with pancreatic cancer by abdominal computed tomography (CT). The examination showed a pancreatic tail cancer and a distal pancreatectomy was performed in 2010. Histopathologically, this tumor was a moderately-differentiated tubular adenocarcinoma. He received gemcitabine adjuvant chemotherapy for a year. In 2012, a chest CT scan revealed 4 nodules in the lower left lobe. We diagnosed gemcitabine-refractory lung metastases after distal pancreatectomy for pancreatic cancer. S-1 chemotherapy was administered as a second line chemotherapy for metastatic pancreatic cancer. After 2 courses of this regimen, the lung metastases were reduced. After 6 courses, a clinical complete response was obtained. Four years and 6 months after the operation, the patient is well without any signs of recurrence, and S-1 chemotherapy is still ongoing. PMID- 26805104 TI - [A Case of Bone Metastasis from Early Gastric Cancer after a Five-Year Disease Free Interval Following Gastrectomy]. AB - A woman in her 50s underwent distal gastrectomy and D1+b dissection in December 2005 for early gastric cancer that was diagnosed as a signet-ring-cell carcinoma, fStage II (T1a, N2, H0, P0, CY0, M0) with 12 lymph node metastases in the second field. Multiple bone metastases were diagnosed on the basis of CT and bone scintigraphy findings and serum ALP elevation (2,743 IU/L) I n December 2010. Fourteen courses of S-1 plus CDDP and 4 mg of zoledronate were administered from January to September in 2011. Pancytopenia, D-dimmer elevation, myelocytes, and metamyelocytes were observed in October 2012, indicating she had bone marrow metastasis. She was treated with a transfusion, anti-DIC therapy, and paclitaxel. She died from gastric cancer in December 2012. We report a rare case of recurrence with bone metastasis from early gastric cancer. S-1 plus CDDP chemotherapy and zoledronate therapy is an effective treatments for multiple bone metastases from gastric cancer. PMID- 26805105 TI - [A Case of Surgical Resection of Isolated Pulmonary Metastasis from Gastric Cancer]. AB - We report a rare case of surgical resection for pulmonary metastasis from gastric cancer. A 71-year-old man underwent total gastrectomy for gastric cancer in October 2012. After the operation, he received S-1 chemotherapy for 1 year. In January 2014, computed tomography of the chest showed a nodule shadow with a cavity at S3 in the right lung. Because it showed a tendency to gradually enlarge, we performed an operation in September 2014. The nodule was diagnosed as metastatic adenocarcinoma from gastric cancer on pathology. The patient is being treated with S-1 chemotherapy during follow-up. The pulmonary metastases of gastric cancer often develop along with carcinomatous lymphangiosis or carcinomatous pleurisy, and isolated pulmonary metastasis is rare. A consensus has not been reached about the usefulness of surgical resection, and the accumulation of further cases is required. PMID- 26805106 TI - [A Successful Case of Treatment of Colonic Metastasis and Peritoneal Recurrence of Type 4 Gastric Cancer by Using Colectomy and Chemotherapy]. AB - We present a successful case of treatment of colonic metastasis and peritoneal recurrence of type 4 gastric cancer by using colectomy and chemotherapy. A 70 year-old woman with a diagnosis of type 4 advanced gastric cancer underwent distal gastrectomy. The final pathological diagnosis was LM, circ, type 4, sig, pT4a (SE), ly1, v1, pN1, M0, P0, CY0, pStage IIIa. Adjuvant chemotherapy was conducted with oral administration of S-1, though regrettably the chemotherapy was interrupted because of diarrhea, an adverse effect of S-1. Metastatic recurrence occurred on the transverse colon, for which she underwent transverse colectomy 2.9 years after the initial surgery. Another colonic metastasis in the ascending colon along with peritoneal recurrence was diagnosed 3.11 years after the initial surgery, and the patient underwent a palliative colostomy and received chemotherapy with S-1 plus docetaxel. She was successfully treated up to a clinical CR with chemotherapy, and she died 5.10 years after the initial surgery. In this case, a good prognosis was obtained through the combination of resection of the recurrence sites, palliative surgery for avoiding obstruction, and chemotherapy using S-1 plus docetaxel for metachronous multiple metastases. PMID- 26805107 TI - [XELOX plus Bevacizumab Chemotherapy for a Patient with Postoperative Recurrence of Colorectal Cancer Under Hemodialysis for Chronic Renal Failure]. AB - We report the case of a patient with a postoperative recurrence of colon cancer who received XELOX plus bevacizumab chemotherapy whilst undergoing hemodialysis. A 73-year-old man had been receiving maintenance hemodialysis for 9 years due to chronic renal failure. At 64 years old, a Hartmann's operation and a posterior segment and segment 3 partial liver resection were performed for sigmoid colon cancer and metastatic liver cancer. Three years 1 months after surgery, local recurrence at the liver invading into the right lung was detected. XELOX plus bevacizumab chemotherapy was administered. After 16 courses of treatment, tumor control was achieved. Chemotherapy with molecular target drugs is currently recommended for advanced/metastatic colorectal cancer; however, a standardized strategy for hemodialysis patients is not established. As the number of hemodialysis patients receiving chemotherapy for some cancers is likely to increase in the future, it will be necessary to consider chemotherapy strategies for hemodialysis patients. PMID- 26805108 TI - [A Case of Long-Term Survival Following Metastasectomies of Liver Metastasis, Lung Metastasis, and Peritoneal Dissemination of Cecal Cancer]. AB - The patient was a 73-year-old woman. She underwent right hemicolectomy and D3 lymph node dissection for cecal cancer in June 2003. Although a peritoneal dissemination was intraoperatively noted around the primary tumor lesion, it was resected concurrently and thus R0 surgery was accomplished. Postoperative adjuvant chemotherapy was not performed. During the follow-up on an outpatient basis, a solitary left lung metastasis was found and partial left upper lobectomy of the lung was performed in December 2004. A solitary liver metastasis was identified in the liver (S3), and lateral segmentectomy of the liver was performed in June 2007. The patient was alive with no evidence of recurrence 11 years and 9 months after resection of the primary lesion and 7 years and 9 months after the hepatectomy. Long-term survival can be achieved by performing resection without residual cancer even in some cases with metachronous metastatic recurrences in multiple organs. Metastasectomy should be considered proactively when the patient is in a good general condition and R0 resection is possible. PMID- 26805109 TI - [Successful Resection of the Peritoneal Dissemination Recurrence of Colon Cancer, Including Metastasis to the Inguinal Hernia Sac--A Case Report]. AB - We report a case of aggressive resection of synchronous and asynchronous peritoneal dissemination of colon cancer, including metastasis to the inguinal hernia sac. A 68-year-old man who was examined for anemia was diagnosed with ascending colon cancer. He underwent right hemicolectomy and resection of the disseminated tumors at the omentum and peritoneum near the Treitz ligament (moderately differentiated tubular adenocarcinoma, pT4a [SE] N0M1P2H0, stageIV). After 1 year 6 months, he was readmitted for intestinal obstruction due to the recurrence of peritoneal dissemination, and underwent partial resection of the ileum, liver, and right kidney. In the CT scan examination before surgery, right inguinal hernia and tumor were identified, and hernioplasty with resection of the inguinal tumor was subsequently performed after intestinal obstruction resolution. All tumors were identified as peritoneal dissemination of the colon cancer tumors by pathological examination. After surgery, he was treated with mFOLFOX6 for 6 months and survived without signs of recurrences despite the absence of treatment. Even in cases of peritoneal recurrence of colon cancer, aggressive resection may improve the prognosis in some cases. PMID- 26805110 TI - [A Case of Resection of Para-Aortic Lymph Node Recurrence and Peritoneal Recurrence Following Sigmoid Colon Cancer Surgery]. AB - In June 2010, a 73-year old man diagnosed with sigmoid colon cancer underwent laparoscopic sigmoidectomy. The histopathological diagnosis was tub2, pSS, n (-), stageII.Vascular invasion was present; however, at the patient's request, no adjuvant chemotherapy was administered.Computed tomography (CT) performed at the outpatient follow-up 4 years and 6 months after the surgery revealed a para aortic lymph node metastasis in the caudal aspect of the left renal artery branch point. No other definite mass shadows were detected. Positron emission (PET)-CT revealed high tracer accumulation (SUVmax) not only in the CT-identified lymph node, but also near the site of the anastomosis in the bowel. Considering that no tracer accumulation was detected at any other sites and the patient's compliance with medication and scheduled visits was poor, surgical resection rather than chemotherapy was adopted as the treatment strategy. No metastases other than at the sites identified by the diagnostic imaging were found during the surgery. Since the findings on palpation did not rule out the possibility that the nodule near the anastomotic site was present inside the intestinal tract, lymph node dissection, resection of the intestinal tract including the anastomotic site, and re-anastomosis were performed. The most likely diagnosis based on the histopathological findings was dissemination for both the adenocarcinoma and the nodule near the anastomotic site. At present, the patient is being treated with adjuvant chemotherapy. In the Japanese Society for Cancer of the Colon and Rectum (JSCCR) Guidelines for the Treatment of Colorectal Cancer, the recommended therapeutic intervention is surgical resection of hematogenous metastases; however, no treatment is specified for lymph node metastases. In general, chemotherapy is administered for distant metastases. However, we have found no reports of cases in which a complete remission has been achieved. There are reports of improvement of survival by surgical resection in cases with solitary lymph node metastasis or isolated dissemination of colorectal cancer. These observations suggest that surgical therapy may have contributed to the improved prognosis in the present case. PMID- 26805111 TI - [A Case of Lateral Lymph Node Recurrence Five-Years after Curative Surgery for Rectal Cancer]. AB - A 62-year-old woman had undergone laparoscopic abdominoperineal resection for rectal cancer in February 2008. The pathological diagnosis was pT2, pN0, M0, pStageI. At her request, she took UFT for 5 years as adjuvant chemotherapy. A CT examination revealed lateral lymph node swelling in January 2014. She was referred to our hospital after a diagnosis of lateral lymph node recurrence. She was administered 6 courses of FOLFIRI plus Cmab as neoadjuvant chemotherapy, after which the tumor size reduced by 62%. The treatment effect was rated as a PR. Laparoscopic right intrapelvic lymph node dissection was performed in July 2014, and the pathological diagnosis was recurrence of rectal cancer in the lateral lymph nodes. We report a case of dissection of lymph node recurrence 5 years after curative surgery for rectal cancer, along with a literature review. PMID- 26805112 TI - [A Case of Brain Metastasis from Rectal Cancer with Synchronous Liver and Lung Metastases after Multimodality Treatment--A Case Report]. AB - We report a case of brain metastasis from rectal cancer a long time after the initial resection. A 62-year-old woman, diagnosed with lower rectal cancer with multiple synchronous liver and lung metastases, underwent abdominoperineal resection after preoperative radiochemotherapy (40 Gy at the pelvis, using the de Gramont regimen FL therapy: 1 kur). The histological diagnosis was a moderately differentiated adenocarcinoma. Various regimens of chemotherapy for unresectable and metastatic colorectal cancer were administered, and a partial response was obtained; thereby, the metastatic lesions became resectable. The patient underwent partial resection of the liver and lung metastases. Pathological findings confirmed that both the liver and lung lesions were metastases from the rectal cancer. A disease-free period occurred for several months; however, there were recurrences of the lung metastases, so we started another round of chemotherapy. After 8 months, she complained of vertigo and dizziness. A left cerebellar tumor about 3 cm in diameter was revealed by MRI and neurosurgical excision was performed. Pathological findings confirmed a cerebellar metastasis from the rectal cancer. Twenty months after resection of the brain tumor, the patient complained of a severe headache. A brain MRI showed hydrocephalia, and carcinomatous meningitis from rectal cancer was diagnosed by a spinal fluid cytology test. A ventriculo-peritoneal shunt was inserted, but the cerebrospinal pressure did not decreased and she died 20 months after the first surgery. Although brain metastasis from colorectal cancer is rare, the number of patients with brain metastasis is thought to increase in the near future. Chemotherapy for colorectal cancer is effective enough to prolong the survival period even if multiple metastases have occurred. However, after a long survival period with lung metastases such as in our case, there is a high probability of developing brain metastases. PMID- 26805113 TI - [Liver Metastasis in a Gastric Cancer Patient--A Case of Successful Radiofrequency Ablation Combined with Degradable Starch Microspheres Transcatheter Arterial Chemoembolization]. AB - A 60-year-old male patient underwent curative surgical resection for gastric cancer. After the surgery, the patient was diagnosed with T4b, N3b, ly3, v2, CY0, fStageIIIc gastric cancer, and adjuvant systemic chemotherapy using S-1 and CDDP was administered. However, follow-up computed tomography (CT) scan examination taken 2 months after surgery revealed a pancreatic fistula and retroperitoneal abscess, and percutaneous drainage was performed. After 1 month, the enhanced CT scan detected liver metastasis measuring 25 mm in diameter at segment 7. The CT guided percutaneous radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) procedure was performed on the liver metastasis using degradable starch microspheres (DSM). Two months after the RFA, a follow-up CT scan revealed local recurrence of the lesion in the medial side of the ablated area in segment 7. A second CT-guided RFA, which was combined with DSM-TACE, was performed on the recurrent lesion. The patient has since survived more than 2 years after the second treatment without any further recurrences. This case report suggests that RFA treatment combined with DSM-TACE might be a safe and feasible treatment for liver metastasis from gastric cancer. PMID- 26805114 TI - [A Case of Gastric Cancer with Multiple Liver Metastases Treated with XP Chemotherapy and RFA Resulting in a Complete Response for a Long Time]. AB - A 60-year-old man underwent total gastrectomy with Japanese D2 lymph node dissection for advanced gastric cancer. The resected specimen was diagnosed as well-differentiated tubular carcinoma, pT3, pN1, cM0, and the final stage was considered as IIB. During adjuvant chemotherapy with S-1 (120 mg/day, administered for 4 weeks and then stopped for 2 weeks), multiple liver metastases were detected by contrast-enhanced CT images 6 months after the operation. Eight courses of XP therapy (capecitabine 1,600 mg/m2/day: day 1-14, cisplatin 70 mg/m2/day: day 1, then stopped until days 15-21) were administered in consideration of the recurrence during adjuvant chemotherapy with S-1, resulting in a partial response. Adverse events such as grade 1-2 abdominal pain, general fatigue, and the resultant deterioration of ADL led to discontinuation of chemotherapy. The residual liver metastasis was treated with RFA therapy, causing it to disappear completely. Serum CEA level was 5.5 ng/mL postoperatively, elevated to 13.9 ng/mL at the time of recurrence and 2.4 ng/mL after XP and RFA therapy. He is doing well without any recurrence 2 years and 6 months later. PMID- 26805115 TI - [Surgical Resection for a Metachronous Liver Metastasis of an Esophagogastric Junction Adenocarcinoma]. AB - The patient was a 56-year-old man with advanced esophagogastric junction cancer. He received neoadjuvant chemotherapy with 5-FU plus CDDP followed by lower esophagectomy and total gastrectomy via the left thoracoabdominal approach in October 2011. Pathological examination revealed EGJ adenocarcinoma (ypT4aN1M0, Stage IIIA, Japanese Classification of Gastric Carcinoma ver.14), and histological analysis indicated Grade 0 (no change). Adjuvant chemotherapy with S 1 was administered. Nevertheless, 6 months after the operation, a solitary hepatic metastasis (f: 32 mm) was detected in S7 of the liver. The patient underwent proton beam irradiation of the liver metastasis, resulting in a complete response, and he was followed up without any chemotherapy. However, 21 months after the irradiation, regrowth of the previous lesion with FDG re accumulation was noted. Given the absence of any neoplasms other than the liver metastasis, right hepatic lobectomy was performed. Pathological examination revealed a small cluster of viable tumor cells surrounded by extensive fibrotic tissue (Grade 2). At 45 months after the initial operation (10 months after the liver lobectomy), the patient is living without any signs of recurrence. Surgical resection for liver metastasis of EGJ cancer may be feasible after careful selection. PMID- 26805117 TI - [A Case of Long-Term Survival in a Patient with Colorectal Liver Metastasis Treated with Multidisciplinary Therapy]. AB - A-71-year-old man underwent right hemicolectomy combined with partial resection of the small intestine and duodenum for an ascending colon carcinoma in July 2009. He presented with a liver metastasis adjacent to the inferior vena cava in November 2009. He received 6 courses of FOLFOX4, but the therapeutic effect was SD, so he underwent an extended posterior sectionectomy combined with partial S8 resection, inferior vena cava resection, and cholecystectomy. He developed remnant liver recurrence in February 2011 and another partial S8 resection was performed. He presented with remnant liver recurrence in October 2011, and radiofrequency ablation and systemic chemotherapy were performed, but were not effective. In June 2013, we performed an extended S8 segmentectomy combined with median hepatic vein and diaphragm resection. He is alive 2 years after the third hepatectomy without any recurrence. Although non-anatomical resection is often performed in repeat liver resections for colorectal liver metastases, sometimes detection of recurrent lesions in the same segment indicates Glisson invasion; therefore, anatomic resection may prolong long-term survival. PMID- 26805116 TI - [A Case of Pancreatic Cancer with Multiple Liver Metastases That Developed Postoperatively and Showed a Complete Response with S-1 Monotherapy]. AB - We encountered a case of pancreatic cancer with multiple liver metastases that developed postoperatively and showed a complete response with S-1 monotherapy for a long time. A pancreaticoduodenectomy was successfully performed on an 80- year old man. Multiple liver metastases developed 6 months postoperatively. Microscopically, the primary lesion was diagnosed as adenosquamous carcinoma with anaplastic carcinoma component, and the final diagnosis was considered to be Stage III disease. S-1monotherapy (80 mg/day, administered for 4 weeks and then stopped for 2-weeks) was effective. A partial response was noted after 3 months, and 9 months after the initial administration of S-1, a complete response was achieved, which persisted for more than 12 months, according to contrast-enhanced CT evaluations.Serum CEA and CA19-9 levels, which became slightly elevated at the time of liver metastasis development, normalized promptly and remained within normal limits. Adverse effects of chemotherapy of more than grade 2 severity were not apparent, and the patient tolerated the 11th course of S-1 administration, consistently. A standard therapeutic strategy and its outcomes in cases of pancreatic cancer recurrence are not clearly outlined in the Japanese Guideline for the Treatment of Pancreatic Cancer. A case of pancreatic cancer with multiple liver metastases that developed postoperatively and showed a complete response with S-1 monotherapy is reported in this paper. PMID- 26805118 TI - [A Case of Combined Modality Therapy for a Cervical Lymph Node Recurrence after Surgery for Esophageal Cancer]. AB - In the present report, we describe a man with type 2 progressive squamous cell carcinoma (cT3N1M0, cStage III) that was detected in the esophago-gastric junction during follow-up after ESD for early gastric cancer. We performed a middle inferior part esophagectomy, a 2-region dissection, and a posterior mediastinum gastric tube reconstruction after preoperative chemotherapy (docetaxel plus cisplatin plus 5-FU). The patient only received 1 course of preoperative chemotherapy because of neutropenia. The pathology results were pT3N2M0, pStage III. Six months later, we started chemotherapy (nedaplatin plus adriamycin plus 5-FU) owing to an abdominal lymph node recurrence. We administered 3 courses, but then switched to radiotherapy because of AEs. After receiving a radiation dose of 50.4 Gy, the patient experienced a para-aortic lymph node recurrence and was administered 50.4 Gy for the new lesion, resulting in a CR. Six months later, we identified lymph node recurrences under the left superficialis neck muscle and performed left cervical lymph node resection. All 3 of the enlarged lymph nodes that we resected were found to contain a metastasis of esophageal cancer. Currently (after 6 months), there are no signs of recurrence. PMID- 26805119 TI - [A Case of an Older Patient with Metastatic Breast Cancer Effectively Treated with Capecitabine, with Achievement of cCR]. AB - A case: An 82-year-old woman underwent Bp plus Ax enforcement for carcinoma of the right breast (T2N1M0, StageIIB) about 5 years previously. Letrozole was administered, but right pleura tuberculum and pleural dissemination was noted in the fifth postoperative year. The hormone therapy was changed, but mediastinal lymph node metastases were observed with tumor marker elevation and bilateral metastases in the lung and right pleural fluid retention. Capecitabine 1,800 mg/day for 3 weeks was started in the sixth postoperative year. The response to treatment was classified as cCR and no side effects were noted. For approximately 1 year and 6 months, no recurrence or metastasis has been observed. Consecutive therapy such as onset of the side effect or an injection method change, dosage weight loss is difficult though chemotherapies is performed for the recurrence metastasis breast cancer case of the older patient. Because capecitabine is isolated, and a continuous administration is had without a side effect, and it was with cCR for this case, in addition, discussion of the literature is reported because it seemed that it may be in effective therapy for an older patient breast cancer case in future. PMID- 26805120 TI - [A Case of Pure Type Mucinous Carcinoma Recurrence after Local Control]. AB - The patient was a 44-year-old woman. Mastectomy and sentinel lymph node biopsy had been performed for carcinoma of the left breast approximately 1 year previously. The diagnosis was mucinous carcinoma, T3N0M0, stage IIB, ER(+), PgR(+), HER2 score 0, Ki-67 20%. Hormone therapy was administered postoperatively. Four months after the surgery, left axilla lymphadenopathy was observed. Chemotherapy with EC and nab-PTX was started for the postoperative lymph node recurrence. To achieve local control, axillary lymphadenectomy was performed within 1 year postoperatively, and 1 metastatic lesion in the lymph nodes was observed. Hormone therapy was started sequentially, with no subsequent recurrence or metastasis. Mucinous carcinomas are classified as a breast cancer subtype. Mixed type, including breast ductal carcinoma, form a large proportion of mucinous carcinomas and the therapy for breast ductal carcinoma is usually administered in such cases. Conversely, pure type mucinous carcinomas rarely show metastasis and have a good prognosis. In this case, however, metastasis was noted and chemotherapy was not completely effective, and local control was achieved with surgical resection. PMID- 26805121 TI - [Hepatic Resection of Multiple Liver Metastases from Gastric Cancer after Molecular Targeted Chemotherapy(S-1 plus Cisplatin plus Trastuzumab)]. AB - A 62-year-old man was diagnosed with gastric cancer and underwent distal gastrectomy, and D1+b lymph node dissection. He was diagnosed postoperatively with T1b (sm2) N0M0, StageIA gastric adenocarcinoma and did not receive any adjuvant chemotherapy after surgery. One year and 6 months after gastrectomy, blood analysis indicated high levels of carcinoembryonic antigen (CEA 262.1 ng/mL) while abdominal computed tomography (CT) revealed multiple liver tumors (S7: 15 mm, S7/8: 20 mm). The patient was diagnosed with metachronous multiple liver metastases from gastric cancer. Chemotherapy, combined with molecular targeted therapy (S-1 plus cisplatin [CDDP] plus trastuzumab), was administered because of overexpression of the human epidermal growth factor receptor 2 (HER2) protein in the primary tumor as assessed by immunohistochemistry, the CEA levels decreased immediately after 2 cycles of the chemotherapy, and the liver metastases shrank markedly with no evidence of new lesions on abdominal CT. However, after treatment, Grade 3 neutropenia and diarrhea were observed. Chemotherapy was suspended and hepatic resection was performed. After hepatic resection, the liver tumors were histologically evaluated as Grade 2 metastatic gastric adenocarcinoma, and the HER2 expression of remnant carcinoma cells was established. The patient has been in good health and remained free of recurrences in the 2 years and 3 months after the liver resection. Surgery with preoperative chemotherapy (S-1 plus CDDP plus trastuzumab) can be an effective treatment for liver metastasis from HER2-positive gastric cancer. PMID- 26805122 TI - [Complete Surgical Resection of a Huge Hepatocellular Carcinoma Invading the Diaphragm and Lung after Transcatheter Arterial Chemoembolization (TACE) and Sorafenib--A Case Report]. AB - We report a case of locally advanced huge hepatocellular carcinoma (HCC) invading the diaphragm and the right lung, which was controlled by sorafenib, thereby allowing curative resection. A 72-year-old man was diagnosed with advanced HCC invading the diaphragm and the right lung. At the time of diagnosis, his tumor was considered unresectable and he underwent transarterial embolization (TAE)/transcatheter arterial chemoembolization (TACE) 3 times. Assessment with enhanced CT after TAE/TACE showed that a viable lesion remained. Subsequently, he was treated with sorafenib for 15 months. Reassessment showed that the main tumor remained stable in size, and he was admitted to our hospital for surgery. Preoperative evaluation by enhanced CT and MRI detected an intrahepatic metastasis in segment 4 of the liver. After TACE was performed for this nodule, extended right hemihepatectomy with right diaphragmatic and right lung partial resection was performed. He had no postoperative complications and was discharged 27 days after surgery. He remains alive without recurrence 10 months after surgery. PMID- 26805124 TI - [R0 Resection by Distal Pancreatectomy with En Bloc Celiac Axis Resection after Down-Staging by FOLFIRINOX Therapy in a Case of Pancreas Cancer--Report of a Case]. AB - The patient, a 55-year-old man, was diagnosed elsewhere as having cancer of the tail of the pancreas and was referred to our hospital. Abdominal computed tomography (CT) revealed a remarkably large tumor, 90 mm in diameter, in the tail of the pancreas, with invasion of the adjacent spleen, stomach, left adrenal gland, diaphragm, and celiac artery; metastasis to the liver; and peritoneal dissemination. The serum levels of the tumor markers CEA and CA19-9 were elevated (21.2 ng/mL and 9,530 U/mL, respectively). Since surgery was not considered to be feasible in this condition, the patient was started on FOLFIRINOX therapy. Adverse events, including Grade 3 decreased neutrophil count, anorexia, diarrhea, and hyperkalemia occurred; however, the patient was able to receive 10 cycles of therapy with downward adjustments of the dosage. In response to the therapy, the tumor marker levels fell rapidly, and on CT, the tumor shrank to 40 mm in diameter; however, resection was still scheduled because positron emission tomography (PET)-CT revealed suspected remnants of the disease in the pancreatic tail. After preoperative transcatheter embolization of the common hepatic artery and the left gastric artery, distal pancreatectomy with en bloc celiac axis resection (DP-CAR) was performed. Intraoperative ultrasonography revealed no metastatic lesions in the liver. Histopathologically, the resected sites were found to be almost totally replaced with fibrous scar tissue, and only trace evidence of moderately differentiated tubular adenocarcinoma components were seen in the pancreatic tail, gastric submucosa, and left adrenal gland. Therefore, R0 resection had been achieved. The patient remains alive, showing no signs of recurrence at 18 months after the initial treatment and 11 months after the tumor resection. The results in this case suggest that FOLFIRINOX therapy can increase the radical curability of pancreatic cancer via down-staging and eventually improve the prognosis. PMID- 26805123 TI - [R0 Resection of Locally Advanced Pancreatic Cancer after Combination Chemotherapy with Gemcitabine and S-1]. AB - A 68-year-old female was referred to our institution in October 2014 for additional therapy for cancer of the head of the pancreas. Utilizing a computed tomography scan, he was initially diagnosed with locally advanced unresectable cancer because of massive invasion to the superior mesenteric artery (SMA). Combination chemotherapy consisting of gemcitabine and S-1 was administrated for 10 months. Since the tumor was remarkably reduced after chemotherapy, pancreaticoduodenectomy combined with portal vein resection was performed. Since the histopathological findings indicated few residual cancer tissues, our chemotherapy was considered dramatically effective. The postoperative course was uneventful and the patient remains well and without any recurrences 14 months after the surgery. We therefore report a case of locally unresectable pancreatic cancer, which achieved R0 resection after combination chemotherapy with gemcitabine and S-1. PMID- 26805125 TI - [Two Cases of Rectal Cancer Resected Curatively after Chemotherapy with CapeOX plus Bmab]. AB - We report 2 cases of locally far-advanced rectosigmoid cancer that were initially unresectable, but were successfully excised after treatment with CapeOX plus Bmab chemotherapy(capecitabine, L-OHP, and bevacizumab). Case 1: A 72-year-old man who complained of severe constipation initially received sigmoid colostomy because of far-advanced rectosigmoid cancer. After 4 courses of CapeOX plus Bmab chemotherapy administration, the size of the primary tumor remarkably decreased and curative resection could be performed. There has been no signs of recurrence for 27 months. Case 2: A 73-year-old man who complained of tenesmus initially received ileostomy because of far-advanced rectosigmoid cancer that directly invaded the appendix, ileum, and urinary bladder. After he received 3 courses of CapeOX plus Bmab chemotherapy, the primary tumor was found to have shrunk remarkably. Therefore, surgery was performed and the tumor was resected curatively. From these experiences, we conclude that some patients with locally far-advanced colorectal cancer can be treated effectively with CapeOX plus Bmab chemotherapy in a neoadjuvant setting. PMID- 26805126 TI - [A Case of Stage IV Rectal Cancer with No Evidence of Disease after Neoadjuvant Chemotherapy and Surgery]. AB - A 46-year-old man presented with hematochezia in October 2012. A circumferential type 2 rectal cancer was detected with colonoscopy. Contrast-enhanced CT showed multiple liver and lung metastases. Chemotherapy was administered after the diagnosis of cStage IV rectal cancer. After 1 course of XELOX plus Bmab, the treatment was changed to XELOX plus Cmab for 21 courses. An infusion reaction occurred during the 21st course. Because a complete response of the liver metastases and a reduction in size of the primary tumor had been achieved, we performed a low anterior resection in April 2014. The final pathological diagnosis was type 2, 10*25 mm, tub1, pMP, int, INF b, pN1 (251). There was no evidence of disease (NED) after the surgery. We are closely following up this patient with no postoperative chemotherapy, and as of July 2015, there is no sign of recurrence. We describe a case of a Stage IV rectal cancer that was resected with radical surgery after neoadjuvant chemotherapy. We also include a brief review of the literature. PMID- 26805127 TI - [Five-Year Recurrence-Free Survival after mFOLFOX6 Administration, Right Hemicolectomy, and Lymphadenectomy for Portal Venous Tumor Thromboembolism]. AB - A 71-year-old woman was admitted for fever and appetite loss. She was diagnosed with ascending colon cancer, with portal vein tumor thromboembolism extending to the portosplenic junction. This was deemed unresectable despite the absence of distant metastasis. She underwent 16 courses of mFOLFOX6 therapy, and because the effect of chemotherapy was PR, right hemicolectomy with high ligation of the ileocolic vessels and the right branch of the middle colic vessels was performed. The tumor stage was yp-T3N1bM0, StageIIIB with a few remaining cancer cells in the portal venous system. Staging after chemotherapy effect was Grade 1a. Postoperatively, 13 courses of mFOLFOX6 were administered. A repeat CT scan showed lymph node recurrence along the SMV, which was subsequently resected again. After the second operation, 9 courses of the DeGramont regimen was administered and discontinued. Five years after the last operation, the patient remains well and without any recurrences. Colonic carcinoma with portal venous tumor thromboembolism has been reported in 9 cases, including ours. Among these, 8 cases involved the ascending colon. Seven of the affected patients were female while 3 were poorly differentiated adenocarcinoma. None of the other patients, except for our case, reported a 5 year patient survival rate without recurrence. PMID- 26805128 TI - [A Case of Para-Aortic Lymph Node Metastases of Sigmoid Colon Cancer Treated with Complete Resection]. AB - We present a case of sigmoid colon cancer with isolated para-aortic lymph node metastasis in a 67-year-old male patient. We treated this patient using simultaneous curative lymph node dissection with primary tumor resection. After inserting a transanal tube and decompressing the proximal colon for obstructive colitis, we performed high anterior resection with paraaortic lymph node dissection without neoadjuvant chemotherapy. The pathology results were as follows: tub2, SE, N3, H0, P0, M1(No. 216, 280), stage IV, curability B. Adjuvant chemotherapy with the XELOX regimen was administered, and the patient remains alive with no signs of recurrence 24 months after surgery. Although simultaneous dissection of para-aortic lymph node metastasis is controversial, curative dissection is advisable for localized cases. PMID- 26805129 TI - [A Case of Unresectable Rectal Cancer Associated with Hemorrhage of the Primary Tumor after Chemotherapy]. AB - A 47-year-old man visited our hospital with complaints of abdominal pain and hematuria.He was diagnosed with unresectable rectal cancer invading the urinary bladder with multiple liver metastases. Systemic chemotherapy with mFOLFOX6 and panitumumab was started soon after sigmoid colostomy. Three months later, both the primary tumor and the liver metastases had partially responded. Another 2 months later, he complained of terrible abdominal pain. CT images revealed a huge primary tumor and hemorrhage in the sigmoid mesocolon occupying the pelvic cavity. A salvage operation was performed and the primary tumor was palliatively resected. Soon after the operation, a local recurrence appeared and grew rapidly. He died 8 months after diagnosis. Rapid growth of the primary tumor seemed a limiting factor for the prognosis. PMID- 26805130 TI - [A Case of Sigmoid Colon Cancer with Metastasis to the Uterus]. AB - A 65-year-old woman complaining of fetor ex vagina was diagnosed with endometrial adenocarcinoma of the uterus based on the pathological findings of an endometrial biopsy. Sigmoid colon cancer was found on a pre-operative CT scan. Diagnosis of double cancer was made and we performed sigmoidectomy and panhysterectomy with associated resection of both adnexa. Histopathological examination found that the tumor accounted for almost all of the uterine mucosa and over half of the muscular layer. Immunostaining showed CK7 (-), CK20 (+), CDX2 (+), ER (-), and PgR (-), and we diagnosed it as a metastasis to the uterus of the sigmoid colon cancer. The pathological diagnosis was a moderately differentiated adenocarcinoma, pT4b (SI: urinary bladder), pN0 (0/12), H0, P1,M1a (uterus), pStage IV. As adjuvant chemotherapy, she was administered XELOX for 6 months. Although colorectal cancer rarely metastasizes to the uterus, due to the increase in the prevalence of colorectal cancer, it may be also increase. To choose the best treatment course, it is necessary to diagnose whether it is a primary uterine cancer or a metastatic uterine cancer. PMID- 26805131 TI - [A Case of Unresectable Advanced Gastric Cancer Treated with Radiotherapy and Trans-Arterial Embolization, Resulting in Effective Hemostasis]. AB - We report the case of a 70-year-old man with unresectable advanced gastric cancer because of invasion to the pancreas and multiple liver metastases. He could have continued with fourth-line chemotherapy by controlling intermittent bleeding from the cancer by means of 2 rounds of radiotherapy and trans-arterial embolization. The serum hemoglobin level declined to 4.5 g/dL during second-line chemotherapy. As the venous bleeding from the cancer was difficult to control by endoscopic hemostasis, radiotherapy with 40 Gy/20 fractions was applied to the cancer. We were able to restart chemotherapy after the hemostasis, but 6 months later, the serum hemoglobin level declined to 6.1 g/dL. Additional radiotherapy of 20 Gy/10 fractions was delivered to the tumor, and successful hemostasis was achieved; the serum hemoglobin level reached 7.5 g/dL. However, a contrast-enhanced CT, which was performed 3 weeks later, demonstrated extravasation from the cancer into the gastric cavity. We conducted trans-arterial embolization, and the patient no longer required transfusion. We planned to restart chemotherapy soon, but after 1 month, he died of pneumonia. PMID- 26805132 TI - [Curative Surgery for Advanced Gastric Cancer with Extensive Lymph Node Metastasis after Long-Term Chemotherapy]. AB - A 65-year-old man was diagnosed with HER2-positive gastric cancer considered unresectable owing to multiple distant lymph node metastases. After long-term chemotherapy, the original lesion disappeared, while peri-gastric lymph node metastases remained. Therefore, we performed lower mediastinal lymph node dissection, total gastrectomy with regional lymph node dissection (D2) and cholecystectomy. Pathological evaluation indicated that the main gastric tumor showed complete response, while there was metastasis in the No.3 lymph nodes, which showed HER2 positivity (3+). At present, the patient has received Xeloda plus trastuzumab and remains relapse-free 5 months after conversion surgery. PMID- 26805133 TI - [Laparoscopic Total Gastrectomy with Adrenalectomy after Neoadjuvant Chemotherapy for Advanced Gastric Cancer with Solitary Adrenal Metastasis]. AB - A 66-year-old man was diagnosed with advanced gastric cancer (cT4a, N0, M1[ADR], cStage IV). He was treated with a triplet neoadjuvant chemotherapy regimen including docetaxel, cisplatin, and S-1, followed by totally laparoscopic total gastrectomy with D2+16a2lat lymph node dissection and adrenalectomy. He had an uncomplicated, good postoperative course and was discharged early from the hospital. S-1 plus cisplatin was started on POD42 as adjuvant chemotherapy. In such cases of solitary left adrenal metastasis from gastric cancer, multidisciplinary treatment comprising perioperative chemotherapy and radical surgery is required. In this report, we demonstrated that totally laparoscopic radical surgery with an uneventful postoperative course allowed the patient to initiate adjuvant chemotherapy in the early postoperative period. PMID- 26805134 TI - [Treatments of Other Cancers and Liver Metastases after Hepatectomy for Liver Cancers]. AB - We examined patients who were treated for another cancer during treatment for primary and recurrent liver cancer. Case 1: A 71-year-old man underwent hepatectomy for hepatocellular carcinoma (HCC). Ten months after the surgery, a pancreatic tumor and multiple liver metastases of HCC were observed. After transarterial chemoembolization was performed to control HCC, the pancreatic cancer was resected. Case 2: A 76-year-old woman underwent liver resection for HCC. Six months after the surgery, gastric cancer and multiple liver metastases of HCC were observed. Transarterial chemoembolization was performed to control HCC, and S-1 was administrated for the gastric cancer. These treatments were repeated for about 1 year with 1 course per 6 week. Case 3: A 59-year-old man underwent hepatectomy for HCC. One year after the surgery, thyroid cancer was detected and was resected. About 7 years after the first surgery, recurrent HCC was noted and resected. Case 4: A 69-year-old man underwent hepatectomy for intrahepatic cholangiocarcinoma (ICC). Two months after the surgery, esophagectomy was performed for synchronous esophageal cancer. Thereafter, hepatectomy was repeated or radiofrequency ablation was performed for liver metastases of ICC. Primary liver cancer is associated with a high recurrence rate. So long as the primary and recurrent liver cancer is properly controlled, treatment for other cancers is possible. PMID- 26805135 TI - [A Case of Liver and Pulmonary Metastases from Adamantinoma, a Bone Tumor]. AB - This case involved a 28-year-old man who had undergone surgery and perioperative chemotherapy for an adamantinoma of the right tibia with multiple lung metastases. Sixteen months after the initial diagnosis, CT revealed an 8 cm diameter liver metastasis and right pneumothorax with little change in the lung metastases. Liver resection and partial pneumonectomy were performed. Pathologic findings confirmed that both liver and lung specimens had metastases from the adamantinoma. Dissimilar from the primary lesion with much interstitial tissue and spindle-shaped cells, the liver metastasis had very dense cell proliferation without interstitial tissue and dominant epithelial parts, suggesting a higher malignant potential. If other lesions are under good control, resection of the newly appearing metastasis, which has a higher malignant potential, might improve prognosis. Further accumulation of cases and detailed studies is required. PMID- 26805136 TI - [A Case of Peritoneal Metastasis in Which Colostomy Was Useful for Restenosis after Stenting]. AB - We report a case of restenosis after performing stenting twice for ileus caused by peritoneal dissemination that occurred after surgery for sigmoid colon cancer, in which colostomy was performed to improve the patient's QOL. The patient was a 58-year-old woman who underwent sigmoidectomy for sigmoid colon cancer. She presented with a peritoneal recurrence 3 times, and the third surgery was a non curative resection. Chemotherapy was administered but was discontinued because of severe adverse events, and the patient was followed up with the best supportive care. An anastomotic stricture occurred 4 years after the initial surgery, and despite performing stenting twice, stenosis occurred 3 times within a few months. The third stenosis occurred shortly after the second episode, and colostomy was therefore performed. The patient died from cancer 4 months after colostomy without having another episode of stenosis. Although stenting is effective for patients with malignant colon stenosis, colostomy appears to be more effective for repeated post-stenting stenosis, when the patient is in an eligible general condition. PMID- 26805137 TI - [Two Effective Cases of Re-Insertion of Self-Expanding Metallic Stent(SEMS)for Re Obstruction of Colon Cancer after SEMS Treatment]. AB - Recently, self-expanding metallic stent (SEMS) have been found to be useful for treatment of intestinal obstruction by colorectal cancer, either as a bridge to surgery or terminal treatment. When SEMS are used for patients in the terminal stage with obstruction due to colorectal cancer, re-obstruction is a severe problem. We report 2 cases of re-insertion of SEMS for obstruction of colon cancer after the first insertion of SEMS. No major problems occurred in either the 2 cases. In the first case, the patient suffered from re-obstruction of colon cancer 6 months after the first SEMS treatment and died 9 months after the second SEMS treatment. In the second case, the patient suffered from re-obstruction of colon cancer 5 months after the first SEMS treatment and died 7 months after the second SEMS treatment. Re-insertion of SEMS for a second obstruction due to colorectal cancer after SEMS treatment is useful for terminal treatment for maintaining QOL. PMID- 26805138 TI - [A Case of Inoperable Advanced Gastric Cancer with Gastric Outlet Obstruction in Which Oral Intake Could Be Prolonged by Duodenal Stenting]. AB - INTRODUCTION: The indications for duodenal stent placement for gastric outlet obstruction caused by gastric cancers remain controversial. We report the case of a patient with inoperable advanced gastric cancer with gastric outlet obstruction in whom oral intake could be prolonged for more than 2 years by duodenal stenting. A 60-year-old man diagnosed as having cStage IV gastric cancer with liver, peritoneum, and lymph node metastases underwent duodenal stent placement before first-line chemotherapy. After 8 months, the duodenal stent was found to be dislocated in the horizontal part of the duodenum due to tumor shrinkage. It was removed immediately by endoscopy. The patient was able to take a solid diet orally for the next 19 months, while receiving systemic chemotherapy. CONCLUSIONS: Duodenal stent placement proved useful in a patient who showed response to chemotherapy, despite the need for management of late complications. This approach is expected to be a first-line treatment option for gastric outlet obstruction caused by inoperable gastric cancer. PMID- 26805139 TI - [A Case of Rectal Stenosis For Gastric Cancer Recurrence Effectively Treated with a Colonic Stent]. AB - A man in his 70s underwent distal gastrectomy and D1 dissection with Roux-en-Y reconstruction in March 2009 for advanced gastric cancer with peritoneal metastasis. He was diagnosed with signet-ring cell carcinoma, Stage IV(T4a, N3a, H0, P1, CY1, M1) and R2. Seventeen cycles of S-1 plus CDDP were administered from April 2009 to December 2010 and 19 cycles of S-1 monotherapy were administered from January 2011 to March 2014. He developed peritoneal recurrence with serum tumor marker elevation in May 2014. Stenosis of the common bile duct, hydronephrosis, and rectal stenosis in Ra-Rs was observed in June 2014. A bile duct stent and a double J catheter was inserted. A colonic stent (NitiTM, 22 mm*6 cm) was also inserted. He could eat after the surgery and was discharged from the hospital. We suggest that a colonic stent is an effective treatment for colon stenosis due to peritoneal metastasis from gastric cancer. PMID- 26805140 TI - [Adult Case of Invagination Due to Small Intestinal Metastases of Malignant Melanoma]. AB - An 84-year-old woman was diagnosed with malignant melanoma after resection of a nasal cavity tumor in February 2008. In April 2010, she underwent small bowel resection because of ileus due to small intestinal metastases. She was diagnosed with ileus again in October 2010. Computed tomography (CT) and 18F fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed invagination of the small intestine and small intestinal metastases. We performed a palliative small bowel resection. She had a good postoperative course and was discharged 2 weeks after surgery. Oral intake was possible for 6 months until her death. PMID- 26805141 TI - [Experience with a Thyroid Carcinoma in Which Symptoms Were Moderated by Local Excision]. AB - Thyroid carcinoma have almost improvement of thing ingredient doing sacculation in a portion is most. We report a case of a giant thyroid carcinoma with a cyst that was operated on. A 64-year-old man showed giant cyst characteristics on cervical ultrasonography, with a mass with calcification on the left lobe. The findings showed an exclusion of tracheal deviation and the esophagus and left total jugular veins were shown. We observed giant calcification in the left lobe center, and the cervical CT laboratory findings showed sacculation on the outside. The cyst showed partial exclusion of the total jugular veins. We preliminarily diagnosed class IV papillary cancer by cytology. The chosen treatment was hypervolemia control on the bottom, plus total thyroidectomy and a lymphodectomy. A perioperative portion of the cyst ingredients was washed away. The whole thyroid gland was firm, and the right lobe showed a tumor. We left one part of the cyst that stuck to a blood vessel in situ. The cervical intracranial pressure, which was the palliative purpose of operating, seemed significantly improved. PMID- 26805142 TI - [A Case of Malignant Phyllodes Tumor Effectively Treated by Radiation Therapy as a Palliative Medicine]. AB - The current report presents the case of a 46-year-old woman with phyllodes tumor metastasis to the anterior chest wall treated by radiation therapy. Although the lesion was not controlled with surgery and chemotherapy, the tumor size markedly reduced after radiation therapy, and bleeding and foul odor from the tumor stopped. Radiation therapy for phyllodes tumor appears to be an effective treatment and should be recognized as one choice of palliative medicine. PMID- 26805143 TI - [A Case Report of Huge Liver Synchronous Metastases of Colon Cancer that Occurred after Right Liver Lobectomy]. AB - We report a patient who experienced a weight loss, general fatigue, and appetite loss and had huge hepatic metastases of colon cancer after right lobectomy for hepatic stone. After 2 courses of treatment with high-dose hepatic arterial infusion of 5-FU (HDHAI; 5-FU 6 g/week), the appetite loss decreased, and low anterior resection was performed. Unfortunately, the other symptoms continued, and she received 5 additional courses of HDHAI during about 6 months. Finally, all of the symptoms disappeared, and she could receive systemic chemotherapy and HAI. Bone metastasis at vertebra TH 9 was observed about 9 months after radiotherapy, and local recurrence at the anastomosis site was observed at about 1 year 1 months after radiotherapy. Both the metastasis and local recurrence were well controlled. Although the lung metastases were growing slowly (number and size), the patient was well enough to go to the hospital on her own and her weight loss almost disappeared. If liver metastases were the most threatening factor of life, HDHAI may be effective for the improvement of symptoms. PMID- 26805144 TI - [Two Cases of Bleeding Advanced Gastric Cancer Treated with Palliative Radiation Therapy]. AB - Case 1: A man in his 70's was being treated with chemotherapy for unresectable advanced gastric cancer. Blood transfusion, endoscopic intervention including argon plasma coagulation, and transcatheter arterial embolization (TAE) were all used to treat repeated tumor bleeding causing anemia, but controlling the bleeding was difficult. In order to control the hemorrhage, radiation therapy of 31 Gy/10 Fr to the cancer was administered. After receiving radiation therapy, the anemia stopped. Case 2: A man in his 70's considered an operation for advanced gastric cancer, but his cardiac performance was poor and it was impossible to perform an operation. We conducted radiation therapy of 39 Gy/13 Fr for the purpose of preventing bleeding from gastric cancer. After receiving radiation therapy, the anemia stopped. We believe that radiation therapy is effective to stop bleeding from gastric cancer. PMID- 26805145 TI - [Four Cases of Primary Small Intestinal Cancer]. AB - Primary small intestinal cancer is very rare. We experienced 4 cases from 2001 to 2013. Case 1: A 46-year-old man presented with abdominal pain and melena. Computed tomography (CT) revealed a tumor in the jejunum. We performed partial resection and lymph node dissection. The histological examination confirmed the diagnosis of moderately differentiated adenocarcinoma, SEN0H0P0M0. He has been recurrence-free for 13 years. Case 2: An 84-year-old woman presented with abdominal pain and vomiting. Gastroscopy showed a tumor in the upper jejunum, and she was diagnosed with adenocarcinoma. Postoperative diagnosis was SEN0H0P0M0. She has been alive for 7 years. Case 3: A 66-year-old woman presented with epigastric discomfort and back pain. Examinations confirmed poorly differentiated small intestinal adenocarcinoma with multiple liver and lymph node metastases. She refused chemotherapy and died 1 month later. Case 4: A 60-year-old man presented with abdominal pain and vomiting. CT revealed a tumor in the jejunum. Gastroscopic biopsy led to a diagnosis of poorly differentiated adenocarcinoma. We performed partial resection but there was extensive lymph node metastasis and peritoneal dissemination (cSIN2H0P3M1) so curative resection was impossible. Two courses of chemotherapy with S-1 and CDDP were administered. However, chemotherapy was not effective. He died 3.5 months after the first operation. Based on 2 of our cases, the prognosis for primary small intestine adenocarcinoma with lymph node metastasis or peritoneal dissemination was poor, with survival of less than 6 months. However, N0 cases without peritoneal dissemination can achieve long-term survival with curative resection. We report these cases with a review of previously reported cases in the literature. PMID- 26805146 TI - [A Case of Small Intestinal Cancer Repeating an Ileus Symptom Complicated with Refractory Arrhythmia]. AB - A 56-year-old man had been treated for hypertrophic cardiomyopathy since childhood. He had been treated for refractory ventricular tachycardia (VT) with interventricular septum cauterization, catheter ablation, and implantation of a defibrillator. He had been treated at home for several years. The ileus that developed in July 2014 was relieved by conservative medical treatment once, but it recurred after oral intake of food a short time later. The obstruction was due to a small intestine cancer that was diagnosed by enteroscopy. After considering the risks of surgery due to the cardiac problem and the quality of life due to ileus caused by the mass, we resected it. This surgery was not a radical resection because of peritoneal dissemination. He started oral food intake postoperatively, and returned to home care. Three months after surgery, oral chemotherapy was administered after considering his stable cardiac function in addition to his coherent mental status. An adverse event of severe watery diarrhea developed, and VT caused by dehydration occurred. After the chemotherapy was discontinued, he recovered in intensive care. He returned to home care at his prior status for 9 months postoperatively. PMID- 26805147 TI - [A Case of Small Bowel Cancer Treated with Laparoscopic Surgery]. AB - We report a case of small intestinal adenocarcinoma treated with laparoscopic surgery. A 70-year-old woman had abdominal pain and epigastralgia. There were no abnormal findings on upper and lower endoscopy. The symptoms continued for 4 months after endoscopy, so she presented to our hospital. After CT examination, small bowel cancer with ileus was suspected. An ileus tube was inserted to relieve the bowel pressure and she was diagnosed with ileum cancer by enteroscopy. Laparoscopic surgery was performed and the pathological stage was determined as pStage IIIa. She was treated with oral chemotherapy (UFT plus LV) and had no recurrence 6 months after surgery. PMID- 26805148 TI - [A Case of Carcinoma of the Uterine Body, Right Ovary, and Duodenum in a Patient with Familial Adenomatous Polyposis]. AB - We report a case of 4 carcinomas of the uterine body, right ovary, and duodenum in a patient with familial adenomatous polyposis (FAP). Her mother's family line carries FAP. She underwent proctocolectomy with ileoanal anastomosis for FAP when she was 20 years old. She was diagnosed with carcinoma of the uterine body and right ovary, and underwent abdominal total hysterectomy, bilateral salpingo oophorectomy, and omentectomy at 48 years of age. The pathological examination revealed endometrioid adenocarcinoma of the uterine body (Stage IB) and endometrioid adenocarcinoma of the right ovary (Stage IA). Her diagnosis was Stage IV according to the Spigelman classification of duodenal polyposis, and she underwent pancreas-preserving total duodenectomy at 50 years of age. The pathological examination was conclusive for 2 carcinomas in the adenoma, which were 20 mm and 25 mm in diameter, respectively. She has been well without any evidence of cancer recurrence 20 months after the pancreas-preserving total duodenectomy. PMID- 26805149 TI - [A Three-Year Survival Case of Extrahepatic Cholangiocarcinoma Treated with Palliative Bile Duct Resection and S-1 Monotherapy]. AB - We report a 3-year survival case of cholangiocarcinoma treated with S-1 monotherapy despite positive margins after palliative bile duct resection. A 66 year-old man visited our hospital for jaundice. Because a smooth round defect was observed in the middle bile duct on ERCP, an impacted stone was suspected. Bile duct incision was performed, but the suspected stone was a tumor that was pathologically diagnosed as cholangiocarcinoma. Although pancreaticoduodenectomy was recommended, the patient decided to undergo palliative bile duct resection. Postoperative pathological examination showed moderately tubular adenocarcinoma with lymph node metastasis. The surgical margins of the hepatic side, duodenal side, and exfoliated surface were all positive. Subsequently, the patient chose to undergo S-1 monotherapy for maintaining his lifestyle. S-1 was orally administered at 100mg/day for 4 weeks, followed by 2 weeks of rest. He has continued S-1 monotherapy and survived for 3 years without evidence of recurrence. PMID- 26805151 TI - [Unresectable Gallbladder Cancer Successfully Treated with Gemcitabine Chemotherapy]. AB - We report a case of unresectable gallbladder cancer successfully treated with gemcitabine (GEM). A 77-year-old man was admitted to our hospital in April 2010 with jaundice. He was diagnosed as having gallbladder cancer that had invaded the liver and hepatic artery, along with lymph node metastasis. The tumor was considered unresectable, and he received chemotherapy with GEM. Each course of treatment consisted of 1,000 mg/m2 GEM administered once a week for 3 weeks followed by a week of no treatment. After the 3rd course, computed tomography revealed reduction in liver invasion and disappearance of lymph node metastasis. After the 18th course, the tumor had completely disappeared, and the patient achieved a complete response. GEM monotherapy was continued for 5 years, even though the tumor had disappeared. The patient is alive and has been disease-free for more than 5 years. PMID- 26805150 TI - [A Case of Resected Gastric Cancer Occurring Simultaneously with Intrahepatic Cholangiocarcinoma after S-1 plus Cisplatin Chemotherapy]. AB - It is sometimes difficult to differentiate between metastatic and primary liver tumors, when the liver tumor occurs simultaneously with a gastric cancer. We encountered a case of resected gastric cancer, which occurred concomitantly with intrahepatic cholangiocarcinoma after S-1 plus cisplatin chemotherapy, in a patient who was previously diagnosed with metastatic liver tumor before treatment. An 80-year-old man was admitted to our hospital because of epigastralgia. Endoscopic study of the upper gastrointestinal tract showed a type 3 tumor at the upper body of the stomach. A plain CT scan showed an irregular, low-density area, which was enhanced by contrast medium in the lateral segment of the liver. We performed an ultrasound- guided needle biopsy, because it was impossible to make a definitive diagnosis by dynamic CT, contrast-enhanced ultrasonography, and MRI. Immunohistochemical analysis for cytokeratin 7/20 resulted in 7 (+)/20 (-) for both the gastric cancer and the liver tumor. Therefore, we diagnosed the patient with gastric cancer, which occurred concomitantly with the metastatic liver tumor, and administered chemotherapy with S-1 plus cisplatin. After 3 courses of the regimen, a reduction in the size of mass was observed in the stomach and the liver. We subsequently performed left hepatectomy and total gastrectomy with lymph node dissection. Microscopic examination revealed the gastric cancer, which occurred simultaneously with the intrahepatic cholangiocarcinoma. The postoperative course was uneventful, and the patient remains well without recurrences. PMID- 26805152 TI - [A Case of Successful Curative Resection Following Downsizing Chemotherapy in Initially Unresectable Locally Advanced Gallbladder Carcinoma]. AB - A 58-year-old woman was referred to our hospital with high fever and right upper abdominal pain. Abdominal computed tomography (CT) revealed a bulky tumor of the gallbladder with liver invasion, metastases to para-aortic lymph nodes, and extensive infiltration to Glisson's sheath. The tumor was initially considered to be unresectable locally advanced gallbladder carcinoma with inflammation, and she received 6 courses of chemotherapy with gemcitabine plus cisplatin. Subsequently, the inflammation was extinguished, and CT showed the main tumor shrunk and the Glisson's sheath infiltration disappeared; however, a liver metastasis existed in segment 5. Thus, S4a plus S5 hepatic segmentectomy with extrahepatic bile duct resection and regional and para-aortic lymphadenectomy was performed. The pathological diagnosis was pT3a, pN1, pM1 (Hep, LYM), fStage IVB. Curative resection was then performed. If selected according to their response to downsizing chemotherapy, conversion therapy might therefore be an effective multidisciplinary treatment for patients with initially unresectable locally advanced gallbladder carcinoma. PMID- 26805153 TI - [A Case of Cholangiocarcinoma with Intestinal Malrotation Treated with Pancreaticoduodenectomy]. AB - We report a case of cholangiocarcinoma with intestinal malrotation that was treated with pancreaticoduodenectomy. The patient was a 74-year-old man, who underwent laboratory screening and was subsequently found to have elevated gammaglutamyl transpeptidase levels. Preoperative ultrasonography revealed intrahepatic bile duct dilatation. Endoscopic retrograde cholangiopancreatography demonstrated a filling defect in the common bile duct and cytology of the bile demonstrated the presence of an adenocarcinoma. On preoperative computed tomography (CT), the SMV was located on the left side of the SMA, which showed the SMV rotation sign. Additionally, the small intestine and the colon were deviated to the right and left side of abdominal cavity, respectively. We diagnosed the patient with cholangiocarcinoma with intestinal malrotation and preduodenal portal vein involvement using the CT scan, and performed pancreaticoduodenectomy. Since the ligament of Treitz was absent during surgery, we diagnosed this as a case of the nonrotation type of malrotation. The postoperative course was uneventful and the patient was discharged from the hospital 42 days after the surgery. Anomalies of the portal venous system are so rare that recognition of its variation is important in order to avoid accidental injuries during the operation. PMID- 26805154 TI - [A Case in Which PTCS Was Effective in the Diagnosis and Treatment of Bile Duct Cancer]. AB - The patient was an 83-year-old man who was admitted for fever and upper abdominal pain as chief complaints. Laboratory tests showed abnormal liver function, and abdominal CT revealed dilation of the common bile duct. The patient was admitted to our hospital with a diagnosis of obstructive jaundice. He underwent surgery, but resection was difficult because of strong adhesion. After dilation of the PTBD fistula, which required approximately 8 weeks, PTCS was performed. Then, according to PTCS and biopsy, bile duct cancer was diagnosed. We were also able to insert a percutaneous biliary stent. The duration of hospitalization was long, but the patient was able to be discharged to his home. Although PTCS requires a long time, it is considered an effective treatment if endoscopic surgery is difficult. PMID- 26805155 TI - [A Case of Intractable Bile Leakage after Surgery for Gallbladder Cancer Successfully Treated by Transcatheter Arterial Embolization]. AB - An 83-year-old man underwent extended cholecystectomy for gallbladder cancer. On postoperative day 13, he developed fever and computed tomography (CT) revealed fluid collection at the cut surface of the liver. Ultrasound-guided fluid drainage was conducted, and he was diagnosed with biliary leakage. Radiological examination using a contrast agent revealed that the anterior branch of the bile duct (B5) was completely interrupted. Simple drainage and ethanol injections into the bile duct proved ineffective. Thus, we performed transcatheter arterial embolization (TAE) in the anterior segmental artery (A5) to stop the production of bile in the injured part of anterior segment. The treatment was effective, and he was discharged 15 days after TAE. TAE might be a useful method for treating intractable interrupted-type bile leakage. PMID- 26805156 TI - [Successful Treatment of Stenosis of the Portal Vein Using an Expandable Metallic Stent after Extended Right Hepatectomy--A Case Report]. AB - We report successful treatment of stenosis of the portal vein caused by enlargement of the remnant liver after extended right hepatectomy with interventional radiology using an intraportal expandable metallic stent (EMS). A 75-year-old man underwent extended right hepatectomy after percutaneous transhepatic right portal embolization for advanced gallbladder cancer. His portal vein branched out into the anterior, posterior, and left branches. The main portal vein and left branch formed a sharp angle by nature. We ligated the posterior branch and sutured the cut line of the anterior branch during surgery. Several days after the surgery, icterus and massive ascites developed. Computed tomography (CT) and portography showed thrombi and stenosis of the cut line of the right branches due to enlargement of the remnant liver. A covered EMS was placed at the stenosis with interventional radiology. After stent placement, the icterus and massive ascites resolved. The patient remains well and EMS has caused no difficulty for 19 months. Intraportal EMS placement is effective in treating perioperative portal venous complications. PMID- 26805157 TI - [Long-Term Multidisciplinary Therapy for Multiple Liver Metastases from Colorectal Cancer with Biliary Drainage for Occlusive Jaundice--A Case Report]. AB - Here, we report the case of a 43-year-old man who was diagnosed with sigmoid colon cancer with synchronous multiple liver metastases following resection of a primary lesion. Subsequent mFOLFOX+BV therapy elicited a marked response in the liver metastases, which led to the patient undergoing hepatic (S7) radiofrequency ablation (RFA), hepatic resection (lateral segmentectomy and partial [S5] resection), and cholecystectomy. Six months later, transluminal RFA was repeated because liver (S7) metastasis recurred, and 8 courses of XELOX plus BV therapy were administered. As obstructive jaundice due to recurrence of the liver metastases developed after a 6 months hiatus in chemotherapy, we endoscopically inserted a biliary stent. Despite reducing IRIS plus BV therapy, obstructive jaundice developed again, and 3 intrahepatic biliary stents were inserted with percutaneous transhepatic biliary drainage. To date, the patient has been alive for 4 years since the initial resection of the primary lesion after undergoing consecutive systemic chemotherapy with different regimens. Some studies have shown that in cases of obstructive jaundice caused by advanced gastrointestinal cancer, longer survival could be expected by reducing the severity of jaundice, suggesting that resuming chemotherapy as well as improving the severity of jaundice could contribute to better outcomes. The patient in the present case was successfully treated twice with biliary drainage for occlusive jaundice and chemotherapy, suggesting that a combination of multidisciplinary therapy and adequate local therapy such as biliary drainage could be important for the treatment of metastatic liver cancer. PMID- 26805158 TI - [A Case of Undifferentiated Carcinoma of the Gallbladder]. AB - In this paper, we present a case of undifferentiated carcinoma of the gallbladder, which is a rare disease with poor prognosis. A 77-year-old woman presented with right hypochondralgia. An abdominal CT scan showed a tumor more than 80 mm in diameter invading the liver parenchyma and transverse colon, and showed liver and lymph node metastases. We diagnosed the patient with stage IV carcinoma of the gallbladder. We resected the gallbladder, S4a plus S5 of the liver, part of the transverse colon, the lymph nodes, the greater omentum, and the extra hepatic bile duct; biliary reconstruction was then performed. Histological examination showed that most areas consisted of undifferentiated cells. The diagnosis of undifferentiated carcinoma was made according to the WHO classification of tumors of the digestive system. No recurrence has been detected for 1 year. PMID- 26805159 TI - [A Case of Neuroendocrine Carcinoma of the Gallbladder]. AB - A 58-year-old woman presented to our hospital with a huge hepatic mass. A CT scan showed an enhanced mass lesion on the fundus of the gallbladder and an enhanced mass ring on the gallbladder bed. Since FDG-PET showed no evidence of metastasis, we performed cholecystectomy, hepatectomy of S4a/5, and regional lymph node dissection. The immunohistochemical study of the specimen was positive for CK7, CK20, chromogranin A, and synaptophysin. The Ki-67 labeling index was 50%, and the SSTR2 score was 2+. The patient was diagnosed with neuroendocrine carcinoma. Since she was in poor condition and on hemodialysis, we started administration of somatostatin analog at the time of recurrence, and soon her diarrhea improved but the tumor increased in size. PMID- 26805160 TI - [A Case of Intrahepatic Cholangiocarcinoma with Invasion to the Transverse Colon and Gallbladder, Forming an Intra-Tumor Abscess]. AB - An 81-year-old man was referred to our institution for evaluation of high fever and a liver tumor that had been detected by ultrasonography. Computed tomography revealed a low-density mass with peripheral ring-like enhancement in S5 of the liver. The liver mass was in contact with the gallbladder, and the boundary between the mass and the gallbladder was unclear. On the suspicion of liver abscess, percutaneous transhepatic drainage was performed. The cavity of the abscess communicated with the gallbladder. Because the cavity had no tendency to reduce in size, we performed surgical resection under a preoperative diagnosis of liver abscess or primary liver carcinoma invading to the gallbladder. Intraoperative findings revealed a liver tumor invading the transverse colon and gallbladder. Subsegmentectomy of S4a and S5 of the liver combined with gallbladder and transverse colon resection was performed. Histopathological findings indicated the growth of a mass forming type intrahepatic cholangiocarcinoma with invasion to the transverse colon and gallbladder, and the pathological stage of the tumor was pT3N0M0, fStage III. Thus far, the patient is alive without recurrence 9 months after surgery. Here, we report an extremely rare case of intrahepatic cholangiocarcinoma that invaded other organs and was associated with an intra-tumor abscess. PMID- 26805161 TI - [Synchronous Triple Malignant Tumors (Hilar Cholangiocarcinoma, Ascending Colon Cancer, Liposarcoma) Resected in a Two-Stage Procedure--A Case Report]. AB - A 70-year-old man with a history of myocardial infarction (MI) and taking 2 antiplatelet drugs was diagnosed with anemia his 6-month post-MI checkup. A lower gastrointestinal endoscopy detected ascending colon cancer, and contrast-enhanced a computed tomography scan revealed hilar cholangiocarcinoma as well as lesions suspicious for gastrointestinal stromal tumors of the small intestine. The patient was given a preoperative diagnosis of synchronous triple malignant tumors. The decision to perform a two-stage procedure was made for the following reasons: the impossibility of discontinuing antiplatelet drugs 6 months after drug-eluting stent placement, continuous bleeding due to colon cancer and the possibility of suffering severe stress from surgery while at high risk for diseases such as hepatic failure. In the initial procedure, a right hemicolectomy and surgical resection of the mesenteric tumor (later diagnosed as a liposarcoma) were performed after portal vein embolization. Confirmation of an enlarged residual liver was confirmed 2 months after the initial procedure. The patient underwent right hepatectomy and resection of the extrahepatic bile duct and the biliary tract was surgically reconstructed. Safe resection of tumors was successfully performed by choosing a two-stage procedure for triple malignancy, including hilar cholangiocarcinoma, ascending colon cancer, and liposarcoma, in a single patient. PMID- 26805162 TI - [A Case of Surgical Treatment for Mixed Adenoneuroendocrine Carcinoma of the Ampulla of Vater]. AB - A 56-year-old woman was referred to our hospital because of epigastric discomfort and jaundice. Contrast-enhanced computed tomography and gastrointestinal endoscopy revealed an ampullary tumor. A biopsy specimen showed adenocarcinoma of the ampulla of Vater. The carbohydrate antigen (CA19-9) level was elevated, but insulin and glucagon levels were in the normal range. Based on a diagnosis of adenocarcinoma of the ampulla of Vater, we performed subtotal stomach-preserving pancreatoduodenectomy with regional lymph node dissection. Postoperative histopathological examinations indicated both neuroendocrine carcinoma (40%) and adenocarcinoma (60%) components in the ampulla of Vater and regional lymph node metastasis. According to the 2010 WHO Classification of Tumours of the Digestive System, the diagnosis of mixed adenoneuroendocrine carcinoma (MANEC) of the ampulla of Vater was confirmed. The patient was treated for 6 months with oral administration of TS-1 as adjuvant chemotherapy. Currently, the patient is alive without recurrence 8 months after surgery. MANEC of the ampulla of Vater is rare. It is a highly malignant tumor, and the standardization of its treatment, including surgery, chemotherapy, and radiotherapy requires further study. PMID- 26805163 TI - [Surgical Resection after Chemotherapy for Ampullary Carcinoma with Synchronous Liver Metastasis--Report of a Case]. AB - A 63-year-old woman presented with abnormalities in liver enzyme levels on laboratory studies, which were detected during a routine medical check-up. She was diagnosed with carcinoma of the ampulla of Vater with a synchronous solitary liver metastasis (S7). She was treated with gemcitabine plus S-1. After 2 courses of the chemotherapy, computed tomography revealed that the primary and metastatic tumors had not changed in size, but new lesions had not appeared. A pylorus preserving pancreaticoduodenectomy and partial resection of the liver (S7) were performed. She received gemcitabine monotherapy for 1 year and she remains alive and well with no evidence of disease 2 year 10 months after resection. PMID- 26805165 TI - [A Case of NET G1 of Vater's Papilla in Familial Adenomatous Polyposis-Associated Duodenal Adenomatous Polyposis]. AB - INTRODUCTION: Familial adenomatous polyposis (FAP) is characterized by the development of duodenal polyposis (DP), which later develops into colonic adenomatous polyps and, eventually, colorectal cancer. Neuroendocrine tumors (NET) are rare in FAP and reports of pancreas-preserving total duodenectomy (PPTD) to treat NET are limited. CASE: A 62-year-old. woman was previously diagnosed with FAP and she underwent a total colectomy and ileorectal anastomosis. Surveillance by upper gastrointestinal endoscopy revealed duodenal polyposis and a 35 mm flat, elevated tumor near the ampulla of Vater. She was diagnosed as having Spigelman stage IV DP and she underwent PPTD. Histopathology revealed a 7 mm NET G1 in the ampulla of Vater and multiple adenomas. DISCUSSION: Little is known about duodenal NET G1in FAP patients who undergo PPTD. Close follow-up is necessary. PMID- 26805164 TI - [Minilaparotomy in Pancreas-Preserving Total Duodenectomy for Familial Adenomatous Polyposis Associated with Spigelman Stage IV Duodenal Polyposis]. AB - INTRODUCTION: Reports on pancreas-preserving total duodenectomy (PPTD) for duodenal polyposis (DP) in familial adenomatous polyposis (FAP) patients are rare. We herein report a case of PPTD performed by minilaparotomy for DP in an FAP patient. CASE: A 27-year-old female FAP patient was diagnosed with Spigelman classification (SC) stage IV DP on gastroduodenoscopy. She underwent PPTD through a 7 cm upper abdominal incision. All polyps were confirmed as adenomas histopathologically. After 6 months of follow-up, complications related to total duodenectomy, such as weight loss, diabetes mellitus, and fatty liver have not been observed. DISCUSSION: SC stage IV refers to non-advanced cancers, and PPTD is basically prophylactic surgery. Therefore, pancreatoduodenectomy seems too aggressive for SC stage IV patients. PPTD by minilaparotomy is suitable for young female patients for its curability, esthetic outcome, and safety. PMID- 26805166 TI - [Signet-Ring Cell Carcinoma of the Ampulla of Vater--Report of a Case]. AB - A 62-year-old man presented with pruritus caused by obstructive jaundice. He was diagnosed with carcinoma of the ampulla of Vater and underwent pylorus-preserving pancreaticoduodenectomy. Histologic examination revealed signet-ring cell carcinoma without nodal metastasis. The patient underwent a partial resection of the small bowel for small bowel obstruction 38 months after the initial resection. Histologic examination disclosed signet-ring cell carcinoma at the surface of the resected small bowel, and the diagnosis of peritoneal recurrence was confirmed. He received oral S-1(100 mg/day) every other day for 14 months until bowel obstruction caused by peritoneal carcinomatosis became apparent. The patient died of the disease 58 months after the initial resection. PMID- 26805167 TI - [Interval Breast Cancer with Neuroendocrine Differentiation]. AB - We report a case of interval breast cancer that was an invasive ductal carcinoma of the breast with neuroendocrine differentiation. The patient was a 66-year-old woman who had a breast lump. She had received breast cancer screening every other year. The last screening was 1 year and 6 months prior to diagnosis. A core needle biopsy for breast tumor led to a diagnosis of invasive ductal carcinoma. Breast conserving surgery plus sentinel lymph node biopsy was performed. The pathological diagnosis from the resected surgical specimen was invasive ductal carcinoma with neuroendocrine differentiation, positive for ER and PgR, and negative for HER2/neu protein expression. The surgical margins were negative, and there was no metastasis in the sentinel lymph node. She was administered radiation therapy and adjuvant endocrine therapy. Two years after surgery, she is well without metastasis. PMID- 26805168 TI - [A Case of a Breast Metaplastic Carcinoma with a Giant Cyst]. AB - A 32-year-old woman was admitted to our hospital for a right breast mass. Ultrasonography showed an 8 cm cystic mass with irregular solid components in the C area. CT showed the 8 cm cystic mass in the right breast, and that the chest wall was compressed by the mass. We performed fine needle aspiration(FNA)of this cyst and prepared a cellblock from the intracystic fluid. These cytological findings were malignant. We diagnosed cancer of the right breast and performed mastectomy and axillary node resection. Histologically, this lesion was diagnosed as a mixed metaplastic carcinoma, composed of squamous cell carcinoma, invasive carcinoma of no special type, and spindle cell carcinoma. Immunohistochemically, estrogen receptor, progesterone receptor, and HER2were negative. Adjuvant chemotherapy(FEC followed by triweekly docetaxel)was administered. There have been no signs of recurrence as of 1 year after the operation. PMID- 26805169 TI - [Axillary Lymph Nodes Metastases from Occult Breast Cancer Recurrence at Ten Years after Resection--Case Report]. AB - We encountered a case of axillary lymph nodes metastases from occult breast cancer recurrence at 10 years after resection. Ten years previously, a 71-year old woman had undergone surgery (dermabrasion+full thickness skin graft+axillary lymph node dissection) for axillary lymph nodes metastases from occult breast cancer. After the operation, she had received chemotherapy and hormone therapy for 5 years. Then, in the recent 5 years, she had stopped attending our hospital. Ten years after the first operation, she came back to our hospital with a lump in her axillary region. She underwent resection for the subcutaneous mass and the axillary lymph nodes. The pathological diagnosis implied metastases from breast carcinoma. We checked up a hole her body. However, we could not detect the original lesion. PMID- 26805170 TI - [HER2-Positive T1a Breast Cancer Metastatic to the Liver and Brain in a Patient Who Died Four Years and Three Months after Mastectomy--A Case Report]. AB - The prognosis of patients with T1a breast cancer is generally good, with a 5-year overall survival rate of 95%. However, HER2 overexpression is a risk factor for recurrence. A 46-year-old woman with left breast cancer underwent a total breast resection. The resected specimen showed invasive ductal carcinoma (T1a, NX, MX, g, ly0, v0, ER [-], PgR [-], HER2 [3+], Ki-67 20%). The patient did not receive adjuvant chemotherapy based on treatment guidelines. Nine months after the mastectomy, multiple liver metastases and severe acute hepatic insufficiency were found. The patient received chemotherapy with trastuzumab and paclitaxel, and a complete response was observed with disappearance of the liver metastases. One year and 11 months after the mastectomy, multiple brain metastases appeared. The patient received whole brain radiation therapy, Gamma Knife radiosurgery, and Cyber Knife radiosurgery. However, the brain metastasis could not be controlled, and the patient died 4 years and 3 months after mastectomy. HER2 positive T1a breast cancer should be observed carefully, and treatment with trastuzumab should be considered. PMID- 26805171 TI - [Treatment for Elderly Breast Cancer Patients Older than 80 Years]. AB - Breast cancer is the leading form of cancer in women in Japan. Cases of elderly women with breast cancer have been increasing rapidly in Japan due to the increasing age of the population. We examined the clinicopathological features and prognosis of breast cancer patients over 80 years old to define an optimal treatment regimen. From January 2004 to October 2014, 43 primary breast cancer patients underwent surgery at the Chiba Rosai Hospital. The median age was 84 years. On pathological diagnosis, the median tumor diameter was 2.4 cm. The tumors were positive for estrogen and progesterone receptors in 30 and 26 patients, respectively. The median overall survival time was 78 months. Only lymph node metastasis was an important predictor of overall survival. It is important to appropriately treat elderly patients. However, there have been no clinical practice guidelines for the management of breast cancer in elderly individuals because of a lack of clinical trials including elderly patients. Elderly patients have other complications such as cardiovascular disease, diabetes, dementia, and pulmonary emphysema. Therefore, we need to make a clinical decision for each individual patient considering comorbidities, functional status, and clinicopathological characteristics of the tumor. PMID- 26805172 TI - [A Case of Peritoneal Metastasis of Breast Cancer Diagnosed by Laparoscopic Assisted Right Hemicolectomy]. AB - The patient was an 86-year-old woman. She underwent right breast-conserving surgery and sentinel lymph node biopsy for breast cancer in August 2006. The pathological diagnosis was invasive ductal carcinoma, T1N0M0, Stage I, ER (+), PgR (-), HER2 (-). She was treated with tamoxifen for 5 years as adjuvant therapy and showed no signs of recurrence. In November 2014, CA15-3 was elevated and an accumulation of FDG in the right paracolic sulcus was observed on PET-CT. Peritoneal metastasis of breast cancer was suspected, and an operation was performed for a definitive diagnosis. During the operation, the tumor was seen on the paracolic sulcus, and laparoscopic-assisted right hemicolectomy was performed. A poorly differentiated adenocarcinoma was diagnosed by pathological examination, and immunostaining results were as follows: CK7(+), CK20(-), mammaglobin (-), GCDFP-15 (-), ER (-), PgR (-), and HER2 (-). Because there was no original lesion other than the breast cancer, the tumor was diagnosed as a metastasis of breast cancer. The frequency of peritoneal metastasis of breast cancer is low. In this case, pathological diagnosis was necessary for a definitive diagnosis. A change of subtype was also confirmed, and the treatment strategy was decided appropriately. Surgical resection should be considered for peritoneal metastasis of breast cancer when the operation can be performed safely. PMID- 26805173 TI - [Long-Term Outcome of Radiofrequency Ablation Therapy for Breast Cancer]. AB - Although radiofrequency ablation (RFA) is promising for the local treatment of breast cancer, data concerning the longterm results are limited. The present study attempted to evaluate the safety and efficacy of RFA and to clarify patient outcomes after treatment. The study included 26 breast cancer patients treated with RFA between 2006 and 2010. There were no acute complications such as burns. All subjects were followed-up after breast radiation and systemic therapies. At the median follow-up period of 88 months, no local recurrence or distant metastases had occurred. After treatment, a hard lump was formed around the ablated area, which gradually decreased in size in all cases (p<0.001). The lumps were calcified in 9 cases. Nipple retraction persisted in 2 cases. However, it is necessary to recognize that a cosmetic result of RFA was not excellent in all cases, RFA appears to be a safe local treatment technique for breast cancer patients. PMID- 26805174 TI - [Study of the Identification Rate of Sentinel Lymph Node Biopsy after Partial Breast Resection]. AB - Sentinel lymph node biopsy using the dye method is generally performed for patients with breast cancer. However, identification of the sentinel lymph node in the mammary gland is occasionally difficult after breast partial resection, as lymph flow is changed under the influence of surgery. Sentinel lymph node biopsy for patients with breast cancer who underwent partial mastectomy without axillary lymph node dissection is grade C1 in the breast cancer clinical practice guideline ver.2 2013. We examined the identification rate of the sentinel lymph node for patients with breast cancer who underwent lumpectomy or partial mastectomy. Lumpectomy and partial mastectomy were performed in 4 and 3 patients, respectively. It was possible to identify the sentinel lymph node in 6 patients, and no metastasis of cancer cells was identified in any patient. In 1 patient who underwent partial mastectomy, it was impossible to identify the sentinel lymph node, and thus, Level Ilymph node sampling was performed. However, the pathological diagnosis was no metastasis of cancer cells. This patient underwent partial mastectomy of the C area and a smaller volume of the mammary gland. Therefore, we consider that lymph flow changed under the influence of surgery. Sentinel lymph node biopsy using the dye method after partial breast resection is useful, but partial mastectomy of the C area makes it difficult to perform sentinel lymph node biopsy. PMID- 26805175 TI - [Effectiveness of Intraoperative Histologic Assessment of Surgical Margins for Breast-Conserving Surgery]. AB - BACKGROUND: The effectiveness of intraoperative histologic assessment of surgical margins for breast-conserving surgery is unclear. In this study, we investigated the effectiveness of intraoperative histologic assessment of surgical margins for breast-conserving surgery. METHODS: Sixty-six patients who underwent breast conserving surgery for breast cancer at our hospital between January 2007 and December 2013 were retrospectively examined for an association between the surgical margin status and locoregional recurrence. The surgical margins were then evaluated by intraoperative histologic assessment. RESULTS: The median observation period was 52 months. Positive margins were found in 14 patients (21%). A total mastectomy was performed in 9 patients, and additional resection in 5 patients. In the permanent tissue sample, the intraoperative assessment was found to be false negative in 2 patients (3.8%), who received boost irradiation postoperatively. No locoregional recurrence was observed in all patients who underwent additional resection or total mastectomy due to positive margins. The rate of margin positivity was significantly higher in invasive lobular carcinomas and in cancers with intraductal extension. CONCLUSIONS: Intraoperative histologic assessment of the surgical margin was useful for reducing the rate of local recurrence. PMID- 26805176 TI - [Seven Cases of Surgery for Breast Cancer under Tumescent Local Anesthesia]. AB - BACKGROUND: Surgical procedures for breast cancer are usually performed under general anesthesia. However, general anesthesia needs to be avoided in some cases due to patient-related factors such as the presence of comorbid diseases. In these cases, we perform surgery under tumescent local anesthesia(TLA)in our department. SUBJECTS: Seven patients who were diagnosed with breast cancer underwent surgery under TLA instead of general anesthesia due to their comorbidities. RESULTS: The planned surgical procedures were successfully completed under TLA. A shift to general anesthesia could be avoided in all cases. The operative procedures for the breasts included modified radical mastectomy (Bt) in 3 cases and wide excision (Bp) in 4 cases. In addition, axillary lymph node dissection was performed in 2 cases; sampling, in 1 case; sentinel lymph node biopsy, in 2 cases; and no procedure for the axilla, in 2 cases. In terms of anesthesia, 2 cases were managed under TLA alone and 5 cases were managed under TLA combined with epidural anesthesia. Lidocaine was used for local anesthesia and did not reach the maximal permissive dose in all cases. No postoperative complication was observed. No local recurrence or new metastasis was observed during the observation period, which ranged from 1 to 67 months after the surgery. CONCLUSION: These findings demonstrate that surgery for breast cancer under TLA is safe and offers high curability for patients at high risk for complications of general anesthesia. PMID- 26805177 TI - [A Case of Spontaneous Regression of Breast Cancer with Multiple Lung Metastases]. AB - Spontaneous regression of any malignant tumor is a rare event, occurring in about 1 of 60,000-100,000 cases of malignant tumor. We report a case of spontaneous regression of breast cancer with multiple pulmonary metastases. The patient was a 73-year-old woman who complained of a left mammary mass. A tumor, approximately 2.2 cm in diameter, was palpated, and breast cancer was suspected based on ultrasound examination. Histopathological findings of the core needle biopsy specimen indicated invasive ductal carcinoma. The patient underwent partial mastectomy with axillary lymph node dissection. It was a stage IIB (pT2N1 [sn] M0) tumor. CT performed after adjuvant therapy confirmed the presence of multiple pulmonary metastases 6 years after surgery. We started anti-cancer therapy with TS-1; however, it was discontinued because an adverse event occurred. Half a year later, tumor shrinkage was confirmed after a recurrence. Four years and 6 months after the treatment was discontinued, the tumor continued to regress spontaneously. PMID- 26805178 TI - [Locally Advanced Breast Cancer Treated with Halsted's Operation Because of Drug Induced Lung Injury Caused by Neoadjuvant Chemotherapy--A Case Report]. AB - A 64-year-old woman discovered a mass in her left breast and visited our hospital. A thorough examination resulted in a diagnosis of left, locally advanced breast cancer (cT4bN3, M0, cStage IIIc) with muscle invasion and Level III lymph node metastases. Because of drug-induced lung disease following 4 courses of adriamycin and cyclophosphamide, the chemotherapy had to be stopped. Halsted's operation and postoperative radiotherapy (50 Gy) were performed. The patient was alive with no evidence of recurrence 9 months after surgery. Although multidisciplinary therapy is recommended in locally advanced breast cancer, chemotherapy sometimes cannot be performed due to factors such as age and physical status. Halsted's operation could be considered as a treatment of choice in patients with locally advanced breast cancer. It is important to choose the treatment strategy based on the condition of the patient. PMID- 26805179 TI - [Subclavian Artery Hemorrhage Related to Everolimus in a Patient with Recurrent Breast Cancer--A Case Report]. AB - A 53-year-old woman underwent breast-conserving surgery for right breast cancer (invasive ductal carcinoma, T1cN0M0, ly+, stage IA, ER+, PR+, HER2-) 5 years previously. During treatment with tamoxifen, massive recurrence in the axillary lymph nodes was found. First- through fourth-line chemotherapy were tried, but they all failed. Everolimus and exemestane were administered, resulting in rapid shrinking of the tumor, but the patient developed sudden severe bleeding from the subclavian artery. Hemostasis was achieved with artery stenting. The patient also developed a thoracic duct-cutaneous fistula. The patient died from tumor regrowth 6.5 months after her first everolimus treatment. Treating tumors involving major vessels with everolimus can cause severe bleeding after rapid shrinking of the tumor. PMID- 26805180 TI - [A Case of Liver Failure Induced by Toremifene in a Patient with Metastatic Breast Cancer]. AB - A 67-year-old woman underwent total mastectomy, postoperative radiation therapy, and adjuvant hormonal therapy more than 9 years 4 months previously. There were no symptoms of recurrence for 3.5 years after completing adjuvant hormonal therapy. A hard mass appeared on the front chest wall and was diagnosed as recurrence of breast cancer histopathologically. A computed tomography (CT) scan revealed multiple metastases in the left side of the chest wall, in the left Level II axillary lymph nodes, and in the left lung. The patient was prescribed high-dose tremifene (HD-TOR 120 mg/day). After less than 4 months, she presented with general fatigue and yellow skin, and was admitted with grade 4 hyperbilirubinemia and grade 3 hepatic dysfunction (AST and ALT). CT and magnetic resonance imaging (MRI) showed no abnormal findings in the liver or biliary tract. Drug-induced liver injury (DILI) caused by HD-TOR was suspected and this therapy was discontinued. The liver dysfunction showed a tendency to improve with conservative treatment and the patient was discharged on the 10th day of illness. She had almost recovered after 5.5 months. A liver biopsy, a drug-lymphocyte stimulation test, and other detailed examinations were not performed, but we judged this case to be one of liver failure caused by HD-TOR-induced DILI. PMID- 26805181 TI - [A Case of Locally Advanced Breast Cancer Treated with Modified Radical Mastectomy with Immediate Reconstruction Using a Tissue Expander after Endocrine Therapy]. AB - We experienced a case of locally advanced breast cancer treated with modified radical mastectomy with immediate reconstruction using a tissue expander after endocrine therapy. A 64-year-old postmenopausal woman had a 50 mm tumor in her right breast with extensive reddening of the skin. She had axillary lymph node metastasis. Core needle biopsy showed invasive ductal carcinoma with positive hormone receptor (ER+, PgR+) and negative HER2 status. The patient was diagnosed with locally-advanced breast cancer (cT4bN1M0, stage IIIB). She was treated with anastrozole at a dose of 1 mg per day. The tumor decreased in size gradually and became operable after 7 months of anastrozole monotherapy. She underwent modified radical mastectomy with immediate reconstruction using a tissue expander. The resected specimen was a 30 mm tumor; adverse effects due to endocrine therapy were of Grade 1a severity. Seven months after adjuvant chemotherapy (FEC->DTX), the tissue expander was removed, and the right breast was reconstructed using an implant. No complications were noted, and the patient was treated with radiation therapy. Ten months have passed since surgery, and no local recurrence or distant metastasis has been noted. PMID- 26805182 TI - [The Case of a Patient with Invasive Lobular Carcinoma with Solitary Metastasis in Pectoralis Major Muscle]. AB - A 44 -year-old woman presented at the outpatient department with a chief complaint of swelling in the right breast. MRI showed a huge breast tumor accompanied by solitary enhanced masses in the pectoralis major muscle. After receiving neoadjuvant chemotherapy, she underwent mastectomy (Halsted operation) and axillary dissection. Pathological examination revealed an E-cadherin-positive infiltrating lobular carcinoma (ILC), and the absence of residual tumor in the muscle was confirmed. In cases of solitary metastasis in the muscle, treatment selection is sometimes difficult. Further research is needed to determine whether surgery contributes to local control in cases of advanced ILC with muscle metastasis. PMID- 26805183 TI - [A Case of Advanced Breast Cancer in Which Marked Improvement of Joint Pain Was Obtained with Stepwise Dose Reduction of Trastuzumab Emtansine (T-DM1)]. AB - A 51-year-old woman had previously received treatment for breast cancer at another hospital but had refused early and aggressive treatment. Therefore, she was treated with symptomatic therapy. As her disease progressed, the patient wished to receive palliative care, and was transferred to a palliative care hospital. However, based on her general condition, it was determined that aggressive treatment should not be abandoned, and she was referred to our hospital for treatment. During her initial visit, the patient was found to have left breast cancer with chest wall invasion, right breast metastasis, multiple liver and lung metastases, left pleural effusion accompanied by pleural dissemination, and left upper limb edema. There was no evidence of bone metastases. The patient's pain was managed with oral oxycodone sustained-release tablets (320 mg daily), using high-dose (80 mg) oral oxycodone hydrochloride hydrate as rescue medication. The results of immunohistochemical testing, confirmed by her previous hospital, were ER (-), PgR (-) and HER2/neu positive. First-line treatment was initiated with paclitaxel (PTX) plus trastuzumab (Tmab), and the response was rated as stable disease (SD). During the course of treatment, she developed drug-induced interstitial pneumonia, which was probably caused by the taxane. Therefore, the first-line treatment was discontinued and T DM1 was initiated as second-line treatment. However, beginning with cycle 3 of the T-DM1 treatment, the patient began complaining of joint pain, mainly in the upper limbs. Therefore, the dose of oxycodone sustained-release tablets was increased to 600 mg per day. However, the patient's joint pain showed no improvement and it was considered unlikely that the pain was due to bone metastases. It was suspected that the pain was an adverse reaction to T-DM1, and the dose of T-DM1 was reduced by one step in cycle 7 of treatment. This resulted in a dramatic improvement of the patient's symptoms. Since oxycodone sustained release tablets was being used at a high dose, sleepiness caused by the drug interfered with her activities of daily living. Consequently, as part of an opioid rotation scheme, topical fentanyl citrate was used concomitantly, and the initial daily oxycodone sustained-release tablets dose of 600 mg was reduced to 40 mg and administered in combination with fentanyl citrate (12mg). These findings suggest that uncontrollable joint pain can occur as an adverse reaction to T-DM1. PMID- 26805184 TI - [A Case of Concurrent Primary Gastric Malignant T-Cell Lymphoma and Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma]. AB - A 71-year-old man was admitted to our hospital for epigastric pain. Upper gastrointestinal endoscopy revealed a type 2- like ulcerative lesion in the posterior wall of the upper and middle part of the stomach. Endoscopic biopsies showed malignant T-cell lymphoma histologically. A chest CT scan revealed a nodule in the apex of right lung, suggestive of primary lung cancer. A total gastrectomy with D2 lymphadenectomy and distal pancreatectomy with splenectomy was performed. Seventy-three days after surgery, the patient developed a lung abscess in the middle lobe of the right lung. A wedge-shaped resection of the upper lobe and total resection of the middle lobe of the right lung was performed. Histological examination revealed a primary pulmonary mucosa associated lymphoid tissue lymphoma in the upper lobe of right lung and an abscess caused by Pseudomonas aeruginosa in the middle lobe of the right lung. Twelve months after surgery the man died of suffocation because of aspiration due to esophageal stenosis caused by progression of metastasis of the paraesophageal lymph node. PMID- 26805185 TI - [A Case of a Metastatic Liver Tumor from a Thymic Carcinoma Detected During a Cesarean Section]. AB - A 40-year-old pregnant woman who had previously been diagnosed with uterine myoma underwent cesarean section. During the operation, a tumor thought to be uterine myoma was found to be an extrauterine tumor arising from the upper abdomen. After the delivery of the fetus, a staging CT scan was performed, which revealed a huge, 18 cm, hepatic tumor in the left lateral segment, a mediastinal tumor with calcification, and multiple lung nodules. She underwent a left hepatic lobectomy and a wedge resection 8 days after the delivery. The initial pathological diagnosis was moderately differentiated neuroendocrine tumor (NET). However, as a primary hepatic NET is extremely rare, further immunohistochemical staining was performed. The tumor was positive for p63, CD5, c-kit, and bcl-2, indicating a diagnosis of thymic carcinoma with liver and lung metastases. PMID- 26805186 TI - [Trans-Arterial Chemoembolization Therapy for Refractory Advanced Non-Small Cell Lung Cancer with Spherical Embolic Material--A Single Case Report]. AB - Here, we report the use of trans-arterial chemoembolization for primary lung cancer. The patient was a 56-year-old woman with refractory Stage IV non-small cell lung cancer who had been treated with repeated systemic chemotherapy. The primary lesion in the right lower lobe was 75 mm in size, with multiple lung metastases. It invaded the right main bronchus and caused severe cough. Radiotherapy was not indicated because of the size and extent of the lesion. During a period of 6 months, chemoembolization of the bilateral bronchial arteries using cisplatin 20 mg, docetaxel 20 mg, and 5-FU 250 mg with HepaSphere (super-absorbent polymer microspheres) was performed 5 times. Twenty mg of docetaxel was loaded onto 25 mg of HepaSphere. The microspheres were between 50 and 100 microns in the dry state. The endpoint of embolization was not stasis but the reduction of arterial flow. There were no serious complications during or after the procedure. Immediately after the first session, the patient's cough was significantly improved. After 5 sessions of the same treatment, the primary lesion was reduced to 48 mm and the level of CEA was reduced from 9.8 to 4.3 ng/mL. The invasion to the right main bronchus was reduced. The patient has been well without any symptoms for 9 months after initiation of trans-arterial chemoembolization. PMID- 26805187 TI - [Pulmonary Mucoepidermoid Carcinoma--A Case Report]. AB - Mucoepidermoid carcinoma (MEC) of the lungs is a rare type of lung cancer, mainly arising from the submucosal salivary type mucous glands of the large bronchi. MEC is classified into low- and high-grade subtypes based on its cytological and histological features, and this classification correlates well with prognosis. We report the case of a 36-year-old man diagnosed after an initial episode of obstructive pneumonia. CT and bronchoscopy revealed an endobronchial mass in the right S3 bronchus and distal atelectasis. Although biopsy is important for deciding the treatment plan, both pre- and intraoperative biopsy resulted in false negativity in this patient. The tumor was completely resected via right upper lobectomy, and the final pathological diagnosis was low-grade MEC. No evidence of disease was found 2 years after the operation without any adjuvant therapy. At (11; 19) translocation with the associated CRTC1-MAML2 fusion oncogene is often recognized in cases of both salivary and pulmonary MEC. It is speculated that MEC is sensitive to EGFR-TKI therapy, which disrupts CRTC1-MAML2 induced proliferation signals via upregulation of the EGFR ligand amphiregulin. PMID- 26805188 TI - [A Case of Metachronous Multiple Thyroid Papillary Carcinoma with FAP]. AB - Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder, the result of a germ line mutation in the adenomatous polyposis coli (APC) gene. FAP can be associated with various extracolonic lesions, including thyroid cancer, which frequently occurs in women. We report the case of a 36-year old woman diagnosed as having FAP with multiple metachronous thyroid papillary carcinomas. She underwent left thyroidectomy at the age of 19 years without a diagnosis of FAP. Multiple polyps in her stomach were detected by medical examination and more than 100 polyps in the colon were found by colonoscopy. She was referred to our hospital after a diagnosis of non-profuse FAP. Multiple tumors with a maximum diameter of 10mm were detected in the right lobe of the thyroid gland during the preoperative examination. Papillary carcinoma was suspected based on fine-needle aspiration cytology. We performed a right thyroidectomy after prophylactic colectomy. Pathological findings revealed a cribriform-morula variant of papillary thyroid carcinoma. The patient remains well after 2 year 6 months with no recurrence. PMID- 26805189 TI - [A Case of Malignant Lymphoma of the Spleen Infiltrating the Diaphragm Treated with Splenectomy]. AB - A 67-year-old man was treated for diabetes mellitus by his family doctor. A splenic tumor was suspected based on his pain in the left side of the abdomen. He was admitted to our hospital for close inspection and medical treatment. Abdominal CT and MRI scans showed a tumor, 10 cm in diameter, in the spleen. An opaque boundary with the diaphragm was also observed. On PET-CT, accumulations of FDG were observed in the left supraclavicular fossa and the left axilla. The serum levels of LDH and sIL-2R were elevated, and therefore a diagnosis of malignant lymphoma was suspected. Due to the risk of splenic rupture, a splenectomy was performed. After pathological examination, the patient was diagnosed with diffuse large B-cell malignant lymphoma. He is currently being treated with chemotherapy at another medical institute. Splenic rupture occurs in some cases of splenic malignant lymphoma, although the number of reported cases is low. In some of the cases, splenic rupture occurred during treatment of the malignant lymphoma. There is no specific way to measure the risk of splenic rupture; however, performing a prophylactic splenectomy is one option in cases where tumor cells have extended to the capsula lienis, similar to that in our patient. PMID- 26805190 TI - [Carcinoma of Unknown Primary Associated with a Sister Mary Joseph's Nodule--A Case Report]. AB - A 72-year old woman visited our hospital complaining of an umbilical mass and a foul smell from the umbilical region. During the evaluation, a massive immobile tumor was palpated in the center of the lower abdomen in addition to an umbilical mass with necrosis. Computed tomography (CT) revealed a massive ovarian tumor accompanied by an umbilical tumor and cyst with peritoneal dissemination, metastases in the liver and spleen and a urachal tumor. There were no symptoms or imaging findings of gastrointestinal obstruction. While searching for the primary focus, it was determined that the ovarian tumor was not of ovarian origin. Under these circumstances, colonoscopy was the only remaining diagnostic modality. However, evaluation of the large intestine was impossible due to compression by the tumor, and diverticulosis of the sigmoid colon did not allow smooth insertion of the colonoscope. Therefore, an excisional biopsy of the umbilical tumor was performed. The most likely diagnoses based on the histopathological findings were colorectal cancer and urachal cancer. Therefore , mFOLFOX6 was selected for chemotherapy because it has been reported to be effective against both urachal and colorectal cancer. At the time of writing, good tumor control had been achieved in the lesions evaluated. Cases of Sister Mary Joseph's nodule have sporadically been reported. The most common primary foci for peritoneal metastases are the stomach, pancreas and ovary. However, in the present case, these sites were ruled out and the primary focus remained unidentified, making it difficult to select appropriate treatment. We present this case with a discussion of the literature. PMID- 26805191 TI - [Successful Surgical Treatment for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus after Favorable Response to Irradiation and Transcatheter Arterial Chemoembolization]. AB - Here, we describe the surgical treatment of a patient with hepatocellular carcinoma(HCC)with portal vein tumor thrombus (PVTT) after irradiation and transcatheter arterial chemoembolization (TACE). A 51-year-old man was being followed-up for HBV-related liver cirrhosis and HCC that was previously treated by radio-frequency ablation (RFA) and TACE. A follow up CT study revealed recurrence of HCC in segment 6 of the liver with PVTT extending to the right branch. As early recurrence was likely after resection and due to insufficient hepatic functional reserve, primary radiotherapy for PVTT was performed followed by TACE. After non-surgical treatment, a favorable tumor response was observed with no evidence of intrahepatic disease within the left lobe of the liver, and the volume of the future liver remnant increased, allowing us to perform splenectomy and right hemihepatectomy combined with portal vein resection/reconstruction. PMID- 26805192 TI - [A Case of Multiple HCC with Vp2 and Vv3 Invasion Controlled by Multidisciplinary Treatment Including Surgery]. AB - The prognosis of HCC with vascular invasion is dismal, but surgery is elected when the hepatic reserve is adequate. The case involved a 68-year-old male HCV carrier. A 10 cm diameter tumor occupying the central 2 segments of the liver and liver metastasis in the left lobe were detected. The patient was diagnosed with multiple HCC with severe vascular invasion of Vp2 and Vv3. The tumor shrunk dramatically after starting HAIC therapy with cisplatin and oral administration of sorafenib. A laparoscopic partial hepatectomy was performed for the viable lesion. The tumor showed almost complete coagulative necrosis. Multiple hepatic metastases were found 4 months after surgery, but the tumor was under control at 25 months after the first HAIC due to HAIC, oral administration of sorafenib, and RFA. An improved prognosis for multiple HCC with severe vascular invasion can be expected by performing multidisciplinary treatments including surgery. PMID- 26805193 TI - [A Case of Hepatocellular Carcinoma with a Vp4 Tumor Thrombus Treated by Multidisciplinary Therapy]. AB - We report a case of hepatocellular carcinoma (HCC) with a Vp4 tumor thrombus treated successfully with multidisciplinary therapy. A 59-year-old woman who complained of abdominal distension was diagnosed as having HCC associated with hepatitis B virus (HBV) infection. The tumor was located in the left lobe, caudate lobe, and S6, and the tumor thrombus extended into the main portal and right portal veins. Extended left lobectomy with thrombectomy and S6 partial hepatectomy were performed after intrahepatic arterial infusion chemotherapy with radiation. During the surgery, the collateral circulation was preserved for bleeding control and residual liver function preservation. The patient was alive 12 months after surgery. Cases of advanced HCC with Vp4 can be successfully treated by multidisciplinary therapy. PMID- 26805194 TI - [Hepatocellular Carcinoma with Vp3 Tumor Thrombosis Treated with Multidisciplinary Treatment--Report of Two Cases]. AB - Hepatic resection of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) at the bifurcation of the portal has the potential to cure the disease. Herein, we report 2 cases of HCC with Vp3 treated with a multidisciplinary approach that might include preoperative transcatheter arterial chemoembolization (TACE) or postoperative hepatic arterial infusion chemotherapy (HAIC). Case 1: A 73-year-old man was diagnosed with HCC with Vp3 located in segment 1 during follow up that was treated by performing a left hepatectomy with removal of the tumor thrombus. After surgery, the patient underwent HAIC, and he was alive without disease recurrence 2 years and 2 months after surgery. Case 2: A 77-year-old man with cirrhotic nonalcoholic steatohepatitis underwent liver resection followed by TACE. However, recurrent HCC with Vp3 was detected in segments 2 and 5, so we performed a repeat liver resection. The patient was alive without disease recurrence 1 year and 8 months after surgery without having received postoperative adjuvant chemotherapy. In select patients diagnosed with HCC with PVTT (Vp3/4), long-term survival can be obtained with multidisciplinary treatment such as surgery and preoperative TACE or postoperative HAIC. PMID- 26805195 TI - [A Case of Surgical Resection of a Liver Metastasis from Colorectal Cancer with a Macroscopic Portal Vein Tumor Thrombus]. AB - The patient was a 65-year-old man. In July 2014, he was diagnosed with rectal cancer in a different hospital and underwent high anterior resection(type 2, T3N0M0, StageII [TMN classification, 7th edition]). During the operation, a small nodule was detected in segment 4 of the liver. Contrast-enhanced abdominal CT revealed a tumor measuring 5 cm in diameter located in segment 4/8 of the liver with a tumor thrombus in the main trunk of the portal vein. In August 2014, the patient was referred to our hospital for further examination and treatment. MR imaging showed a lobulated tumor located in segment 4/8 of the liver. Gadoxeticac id-enhanced hepatobiliary phase MR imaging showed that the tumor was less enhanced than was the adjacent liver parenchyma. 18F-FDG-PET/CT demonstrated abnormal accumulation of 18F-FDG in the main tumor(SUVmax=18.3). There was no obvious abnormal accumulation in the other organs. In September 2014, he underwent extended left hepatectomy and portal vein tumor thrombectomy. The resected specimen showed a well-differentiated adenocarcinoma. Immunohistochemical staining results were CK7/CK20 (-/+) and CDX2 (+), which suggested that the tumor was derived from the gastrointestinal tract rather than the liver. The pathological diagnosis was a liver metastasis from rectal cancer. In the 6 months after the operation, intrahepatic recurrence was detected, and the patient was treated with systemicchemotherapy. PMID- 26805196 TI - [Surgical Resection for Mediastinal Lymph Node Metastasis of Combined Hepatocellular and Cholangiocarcinoma--A Case Report]. AB - We report the case of a 77-year-old woman with mediastinal lymph node metastasis of combined hepatocellular and cholangiocarcinoma who was successfully treated with S8 segmentectomy and lymphadenectomy. A hepatic nodule was detected in segment 8 during follow-up computed tomography (CT) after left iliac arterial aneurysm repair. The patient was diagnosed with a hepatocellular carcinoma (HCC), and transcatheter arterial chemoembolization (TACE) was selected for HCC because of the patient's condition. The levels of tumor markers did not change after TACE was performed twice. Therefore, TACE treatment was considered to be ineffective for HCC, and the patient was admitted to our hospital for surgical resection. In addition to the primary lesion, a lymph node with a diameter of 20 mm was detected in the anterior mediastinum using CT and magnetic resonance imaging(MRI). We did not find any other metastases, and therefore, S8 segmentectomy and lymphadenectomy in the anterior mediastinum were performed. Recovery was uneventful, and the patient was discharged from the hospital on postoperative day 12. Based on histopathologic findings, combined hepatocellular and cholangiocarcinoma with mediastinal lymph node metastasis was confirmed. Levels of tumor markers normalized, and the patient survived without recurrence for 6 months. PMID- 26805197 TI - [A Case of Solitary Paraaortic Lymph Node Recurrence after Surgical Resection for Combined Hepatocellular and Cholangiocarcinoma]. AB - A 46-year-old woman underwent right hemihepatectomy, cholecystectomy, and sampling of the hilar lymph nodes for combined hepatocellular and cholangiocarcinoma. She received oral S-1 after hepatectomy. However, her serum level of carcinoembryonic antigen gradually increased, and solitary paraaortic lymph node recurrence was detected on positron emission tomography-computed tomography 12 months after hepatectomy. The patient underwent paraaortic lymph node dissection. Histologic examination revealed solitary paraaortic lymph node metastasis composed of hepatocellular carcinoma. After paraaortic lymph node dissection, she was administered sorafenib, and she remains alive and healthy with no evidence of disease 17 months after the initial resection. PMID- 26805198 TI - [Long-Term Survival of a Case of Quadruple Cancers with Cholangiocellular Carcinoma]. AB - The patient was an 82-year-old man, who contracted chronic hepatitis C in 1977. In 1997, he was diagnosed with intraductal papillary-mucinous neoplasm (IPMN), and was treated with surgery. In August 2005, cholangiocellular carcinoma (CCC) and hepatocellular carcinoma (HCC) were detected, and he underwent a subsegmentectomy of the liver. In February 2007, he had a supradiaphragmatic lymph node recurrence of CCC. It was a solitary lesion; therefore, we resected the recurrent tumor by thoracoscopic surgery. In January 2012, squamous cell lung cancer was detected and he had a thoracoscopic operation. Furthermore, in February 2015, 2HCCs were detected in S5 and S5/8 of the liver. He underwent radiofrequency ablation. Over the course of 18 years, this patient developed cancers in his pancreas, intrahepatic bile duct, liver, and lung. However, the patient has survived without recurrence because of aggressive therapy and diligent surveillance after surgery. PMID- 26805199 TI - [A Case of Extrahepatic Hepatocellular Cancer Discovered during Gynecological Laparoscopic Surgery]. AB - Recently, laparoscopic surgery has become increasingly popular because of its lesser invasiveness, including smaller incisions, and fewer post-operative complications. It is also possible to observe the abdominal cavity by laparoscopy. We report a hepatocellular carcinoma arising in an accessory liver lobe detected during gynecological laparoscopic surgery. A 48-year-old woman who was undergoing laparoscopic hysterectomy for uterine fibroids was found to have a protruding, extrahepatic pedunculated tumor by intraoperative observation of the abdominal cavity during the fibroid procedure. We suspected FNH based on preoperative imaging findings, including abdominal ultrasound, computed tomographic scanning, and magnetic resonance imaging. We performed a laparoscopic partial hepatectomy. The cut surface of the tumor was similar to normal liver tissue. The pathological findings identified normal liver tissue and vessels, suggesting it was the accessory liver lobe. It also included a well differentiated hepatocellular carcinoma. The final diagnosis was hepatocellular carcinoma arising in the accessory liver lobe. There have been no prior reports of extrahepatic liver tissue detected during gynecological surgery. This case reminded us of the importance of intra-abdominal observation during laparoscopic procedures. The opportunities to discover other cases of extrahepatic liver tissue by laparoscopy will increase. PMID- 26805200 TI - [Resected Focal Nodular Hyperplasia That Was Difficult to Differentiate from Hepatocellular Carcinoma--A Case Report]. AB - We report a case of a 62-year-old woman with a growing liver tumor that was difficult to differentiate from hepatocellular carcinoma (HCC). Abdominal CT revealed a hypervascular tumor (36 mm in diameter) in segment 3 of the liver that showed early enhancement and which had grown from 30 mm to 36 mm over the previous year. A fatty liver and gallstones were also detected. Magnetic resonance imaging (MRI) showed high intensity staining of the tumor on both T1- and T2-weighted images, and EOB-MRI revealed a mass that showed high signal intensity in the hepatobiliary phase. The imaging findings were not typical for HCC; however, the possibility of malignancy could not be ruled out due to the enlargement of the mass. Therefore, in February 2015, we performed a laparoscopic left lateral segmentectomy with cholecystectomy. After a good postoperative course, the patient was discharged from the hospital 11 days after surgery. Histological assessment revealed the tumor was focal nodular hyperplasia (FNH). PMID- 26805201 TI - [Long-Term Survival with Multidisciplinary Therapy for Rectal NET with Liver Metastases--A Case Report]. AB - We report a case of a 71-year-old man with liver metastases from a rectal neuroendocrine tumor(NET). The patient's chief complaint was melena. He was diagnosed with rectal carcinoma with liver metastases during his initial visit. Therefore, we started UFT/LV as first-line chemotherapy. After 2 courses, the patient's disease had progressed, so the treatment was changed to S-1 as second line chemotherapy. The patient showed a partial response. In February 2010, we performed an anterior resection, and in April 2010 we performed a posterior segment and S2/8 partial hepatectomy. Histopathological examination showed rectal NET with liver metastases. In December 2011, multiple liver metastases were found, and multimodal treatment including TACE, RFA and somatostatin analogues was selected to treat the recurrent tumor. The patient survived for 10 years after his first visit and for 3 years and 6 months after the recurrence. Multidisciplinary therapy was effective for treating rectal NET with liver metastases. PMID- 26805202 TI - [New FP Therapy Was Effective for a Case of Massive Hepatocellular Carcinoma]. AB - A 62 year-old woman was hospitalized with the diagnosis of pneumonia, and a huge mass was recognized in the right lobe of the liver during a CT scan. AFP and PIVKA-II were elevated to 101.05 ng/mL and 2,177 mAU/mL. The liver function test indicated Child-Pugh classification A, liver damage degree B, and ICG R15 34%. We judged a radical cure resection impossible. We treated the patient with arterial injections of modified new FP therapy. No side effect occurred during the first course. Liver dysfunction with fever and hematuria occurred during the second course, leading to discontinuation of therapy. Because a prominent reduction in the size of the tumor was achieved, liver resection is scheduled. New FP therapy can be expected to attain a favorable result that may allow for curative resection of the tumor. PMID- 26805203 TI - [Combination Chemotherapy Using Sorafenib and Hepatic Arterial Infusion with a Fine-Powder Formulation of Cisplatin for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis--A Case Report]. AB - Sorafenib has been a standard therapy for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis. Hepatic arterial infusion chemotherapy (HAIC) is still preferably performed in Japan because of its relatively good tumor shrinking effect. We report a case of advanced multiple HCC with portal thrombus that responded to combination chemotherapy with sorafenib and repeat hepatic arterial infusion with a fine-powder formulation of cisplatin (IA-call(r)). A 57 year-old man presented for the treatment of HCC with alcoholic cirrhosis. Multiple HCC were found to be rapidly progressing with portal thrombosis. HAIC with IA-call(r) was performed, but the tumors progressed. TAE was performed 3 times thereafter and the main tumor shrunk to some extent. A month after the last TAE, the HCC was found to progress again, and oral sorafenib was administered. A reservoir and catheter were placed and HAIC with low-dose 5-fluorouracil and cisplatin was performed for 3 cycles following 1 HAIC cycle with epirubicin and mitomycin C, which was not effective. For 10 months after initial therapy, HAIC using IA-call(r) has been performed once for 6 weeks. After performing HAIC with IA-call(r) 5 times, the serum levels of HCC tumor markers AFP and PIVKA IIdecreased, and the tumors continued to shrink and were not stained on enhanced CT scan. The patient has been alive for 23 months after the initial therapy and has maintained stable disease. PMID- 26805204 TI - [Relapse-Free Survival Following Multidisciplinary Therapy for Hepatocellular Carcinoma with Multiple Lung Metastases--A Case Report]. AB - Chemotherapy is not effective for metastatic hepatocellular carcinoma(HCC); however, prolonged survival can be expected for patients with multiple metastases who are treated with surgical resection in addition to chemotherapy. We present a case of a 36-year-old woman with hepatitis B who developed HCC with multiple intrahepatic and lung metastases after undergoing resection of HCC in 2010 in Canada. The patient returned to Japan for additional treatment. She was treated with TACE therapy and systemic chemotherapy, but her lung metastases did not improve. The patient's PIVKA-II levels remained moderately elevated after initiation of chemotherapy. Therefore, we performed surgical resection of the lung metastases in March 2014. Five months later, the patient received additional TACE therapy when an isolated metastasis was found in the residual liver. Since then, no recurrence of HCC has been found, and the patient's PIVKA-II levels have remained in the normal range. This case demonstrates that surgical resection for multiple lung metastases is possible in select patients. PMID- 26805205 TI - [Laparoscopic Liver Resection for HCC Recurrence]. AB - Laparoscopic surgery is less invasive and provides better cosmetic outcomes than conventional surgery. Laparoscopic liver resection has been covered by insurance since April 2010 and is increasingly performed in many hospitals. However, laparoscopic hepatectomy is sometimes difficult to perform safely in the case of HCC recurrence because adhesions restrict vision and manipulation of forceps. We report the results of laparoscopic hepatectomy for cases of HCC recurrence. From June 2010 through December 2014, 180 laparoscopic hepatectomy procedures for HCC were performed in our hospital; 33 were in patients with HCC recurrence. Of the 33 patients, 26 underwent pure laparoscopic partial hepatectomy. The median operative time was 242 min, the median bleeding amount was less than 5 g, and the median hospital stay after surgery was 12.0 days. In the group that underwent laparoscopic hepatectomy after open liver resection (12 patients), the median operative time was 303.5 min, the median bleeding amount was less than 5 g, and the median hospital stay after surgery was 9.0 days. Among the 21 patients that underwent laparoscopic hepatectomy after laparoscopic liver resection, the median operative time was 248 min (p=0.382), the median bleeding amount was less than 5 g (p=0.112), and the median hospital stay after surgery was 11.0 days (p=0.236). We could perform laparoscopic hepatectomy for cases of HCC recurrence. This procedure can be suitable for HCC recurrence, which sometimes requires poly surgery. PMID- 26805206 TI - [Effect of Preoperative Bowel Preparation on Surgical Site Infection in Liver Surgery]. AB - BACKGROUND: In our institute, the protocol for preoperative bowel preparation before liver surgery has been changed from polyethylene glycol lavage (NiflecR: N group) to magnesium citrate (MagcorolR: M group). METHODS: Ninety patients who underwent hepatectomy without reconstruction of the bile duct, gastorectomy, or colorectal resection from 2012 to 2013 were enrolled in this study. The impacts of preoperative bowel preparation were compared between the 2 groups. RESULTS: There were no significant differences between the 2 groups in terms of surgical procedure, operative time, bleeding amount, and duration of postoperative hospital stay. Surgical-site infection did not occur in both groups. There were no significant differences in the white blood cell count and platelet count of the patients in both groups. The C-reactive protein level in the M group was significantly lower than that in the N group on days 1, 3, and 5 after the operation, whereas the ammonia level in the M group was significantly lower than that in the N group on day 5 after the operation. CONCLUSION: It is possible to simplify preoperative bowel preparation associated with liver surgery while ensuring appropriate safety. PMID- 26805207 TI - [A Case of Synchronous Multiple Esophageal Cancers Composed of Squamous Cell Carcinoma and Barrett's Adenocarcinoma]. AB - A 67-year-old man was admitted to our hospital for treatment for multiple superficial esophageal cancers. Screening upper gastrointestinal endoscopy examination revealed a superficial squamous cell carcinoma (SCC) at the middle thoracic esophagus and Barrett's epithelium and a superficial adenocarcinoma at the abdominal esophagus. We performed a subtotal esophagectomy with gastric tube reconstruction via the retrosternal route. Pathological examination revealed a Barrett's adenocarcinoma at the abdominal esophagus. Esophageal cancer is thought to be a multicentric disease, and we sometimes find multiple esophageal cancers. In Japan, most cases of multiple esophageal cancers are composed of SCCs, and the occurrence of multiple esophageal cancers composed of SCC and Barrett's adenocarcinoma is rare. In contrast, the number of the patients with Barrett's esophagus is increasing, and the number of the patients with Barrett's adenocarcinoma also seems to be on the rise. Therefore, it is important be aware of the possibility of multiple esophageal cancers composed of SCC and Barrett's adenocarcinoma while making diagnoses. PMID- 26805208 TI - [A Case of Long-Term Survival of Advanced Esophageal Basaloid Squamous Carcinoma Invading the Trachea]. AB - A woman in her 50s complained of dysphagia and was diagnosed with locally advanced esophageal cancer in the middle and upper thoracic esophagus, invading the tracheal bronchus. The biopsy indicated esophageal basaloid squamous carcinoma. The pretreatment diagnosis was cT4N2M0, cStage IVa. She was treated with systemic chemotherapy consisting of FAP (5-fluorouracil [5-FU], doxorubicin [DXR] and cisplatin[CDDP]), which resulted in significant tumor shrinkage. One year later, the tumor regrew, and nedaplatin (CDGP) plus docetaxel (DOC) was administered as second-line chemotherapy. The patient complained of dysphagia during the course of chemotherapy, and received radiation therapy for the residual tumor, which again significantly shrunk. Four years after the first round of chemotherapy, the patient can take oral nutrition, and is continuing to undergo chemotherapy. This is a case of long-term survival of locally advanced esophageal cancer of basaloid squamous carcinoma. Effective chemotherapy and radiation can improve the treatment outcome. PMID- 26805209 TI - [A Case of Esophageal Cancer Metastases to the Skin]. AB - Skin metastases from esophageal cancer are comparatively rare but have poor prognosis. Here, we report a case of esophageal cancer metastases to the skin. A 70-year-old man was admitted to our hospital for nodules with ulceration in the nose, and biopsy revealed a metastatic carcinoma. FDG-PET indicated FDG accumulation in the skin, liver, and esophagus, while an endoscopic study of the upper gastrointestinal tract showed a type 3 tumor at the upper mid-thoracic esophagus. We diagnosed the patient with metastatic esophageal cancer and administered chemotherapy. Radiation therapy (40 Gy/20 Fr) was simultaneously administered for the tumor in the nose because the patient's quality of life (QOL) decreased daily owing to pain and bleeding caused by metastatic skin cancer. The radiation therapy reduced the size of the tumor in the nose, but the tumor had remained along with the presence of a scar 3 to 6 months after the start of radiation therapy. Radiation effectively promoted the QOL of our patient with skin metastases. PMID- 26805210 TI - [Basaloid Carcinoma of the Esophagus with Lugol-Voiding Lesions--A Case Report]. AB - Patients with Lugol-voiding lesions of the esophagus are frequently affected with multiple cancers. Basaloid carcinoma of the esophagus is a very rare disease characterized by growth in the submucosal layer that exhibits a submucosal tumor like shape. There have been some reports that this type of carcinoma is biologically high-grade. We report a case of metachronous squamous cell carcinoma in situ and superficial basaloid carcinoma in the esophagus with Lugol-voiding lesions. A 63-year-old man underwent gastrectomy for gastric cancer at the age of 45 years. The subsequent surveillance endoscopy found a type 0-IIc lesion in the esophagus in 2000. EMR was thus performed. The pathology showed squamous cell carcinoma in situ. Dysplasia was diagnosed based on the Lugol-voiding lesions, and EMR was performed twice. In 2014, a fourth EMR was performed after a high grade intraepithelial neoplasia was diagnosed. The pathology showed squamous cell carcinoma in situ and a basaloid carcinoma in the lamina propria, T1a-LPM, ly0, v0, pHMX, pVM0. The patient has had no recurrence for approximately 1 year after the fourth EMR. PMID- 26805211 TI - [A Case of Solitary Brain Metastasis from Stage 0 Esophageal Carcinoma after Neoadjuvant Chemotherapy Followed by Surgery]. AB - Esophageal carcinoma rarely metastasizes to the brain. We experienced a case of solitary brain metastasis from Stage 0 esophageal carcinoma after surgery. A 54 year-old man was diagnosed with esophageal carcinoma (clinical T3N2M0, cStage III). He received neoadjuvant chemotherapy consisting of 5-fluorouracil plus cisplatin followed by subtotal esophagectomy with dissection of 3 regional lymph nodes. The pathological diagnosis was poorly differentiated squamous cell carcinoma, CTpT1a- EP (T2), pN0, sM0, fStage 0. The pathological response of neoadjuvant chemotherapy was Grade 2. Eight months after surgery, abnormality of the right frontal lobe was identified with positron emission tomography(PET). Brain magnetic resonance imaging (MRI) uncovered a solitary 25 mm lobular tumor at the right frontal lobe, although no evidence of local recurrence or other metastatic sites was found. Gamma knife therapy was performed for the brain metastasis.He has survived for 35 months after esophagectomy without other metastases. PMID- 26805212 TI - [A Case of Carcinosarcoma of the Esophagus Treated with Chemoradiotherapy]. AB - Carcinosarcoma of the esophagus is a rare malignant neoplasm. We report a case of an 87-year-old man treated with chemoradiotherapy. The main presenting complaint was hiccups. Histological analysis of a biopsy from the tumor demonstrated a carcinosarcoma. The clinical diagnosis was T2N0M0, cStageII. In consideration of his advanced age, a past history of cerebral infarction, high blood pressure, aortic valve sclerosis, and chronic renal failure (Cr 1.5-1.8 mg/dL), chemoradiotherapy consisting of TS-1 40 mg/day with radiotherapy of 66 Gy was administered to the patient. The carcinosarcoma decreased in size on endoscopic examination in response to the chemoradiotherapy. Surgery with extended lymphadenectomy for esophageal carcinosarcoma is the standard treatment, but chemotherapy may be a good choice for local control for patients who cannot undergo surgical resection. PMID- 26805213 TI - [A Case of Esophageal Carcinoma with an Aberrant Right Subclavian Artery]. AB - We report a rare case of esophageal carcinoma with an aberrant right subclavian artery. A 67-year-old woman was admitted to our hospital because of a sense of discomfort during swallowing. A detailed gastrointestinal examination revealed advanced carcinoma of the middle thoracic esophagus. Preoperative CT also revealed an aberrant right subclavian artery (AR SA). After the second course of neoadjuvant chemotherapy (FP therapy), we conducted a transthoracic esophagectomy with a 3-field lymphadenectomy. The right recurrent nerve was not identified at the right subclavian artery during mediastinal dissection, but the non-recurrent inferior laryngeal nerve (NRILN) was identified as going directly from the vagal nerve to the larynx during the neck lymphadenectomy. The thoracic duct ran between the esophagus and the azygos vein, terminating at the right venous angle. We were able to perform a #106recL lymphadenectomy as usual. She continues to do well without signs of recurrence 1 year later. Though ARSA is a relatively rare congenital anomaly, it must be identified preoperatively, and anatomical anomalies such as NRILN must be taken into consideration, in order that the operation can be performed safely. PMID- 26805214 TI - [A Case of Esophageal Cancer Complicated with Idiopathic Thrombocytopenic Purpura]. AB - The patient was a 58-year-old woman. She was diagnosed with idiopathic thrombocytopenic purpura (ITP) when she was 41 years old. Splenectomy was performed at age 55; however, there was no response (NR). Therapy with prednisolone was continued. She underwent endoscopic examination because of dysphagia, and an esophageal tumor was revealed. She was diagnosed with esophageal squamous cell carcinoma (Mt, cT3N1M0, Stage IIIA). She received high dose g-globulin therapy and platelet transfusion before surgery, and the platelet count subsequently increased to 11.0*10(4) mm3. A subtotal esophagectomy was performed. The platelet count was low immediately after surgery; however, it increased after POD5. The patient was discharged without complications. She is alive without recurrence 9 years after surgery. This is the first report of esophageal cancer complicated with ITP that was not responsive to splenectomy. We report this case along with a discussion. PMID- 26805215 TI - [A Case Report of Reoperation for Intractable Obstruction of the Stomach after Surgery for Esophageal Cancer]. AB - Although esophageal reconstruction using the stomach is common in surgery for esophageal cancer, this procedure sometimes results in delayed gastric emptying and reflux. This is a case report of reoperation for intractable obstruction of the stomach after initial esophageal surgery in a 59-year-old man. The obstruction was resistant to conservative management. We resected the duodenum, preserving the vascular pedicle of the right gastroepiploic vessels, and performed reconstruction with a Roux-en-Y procedure in the second operation. There was marked improvement in gastric emptying. PMID- 26805216 TI - [A Case of Removable Self-Expandable Metallic Stent(SEMS)Placement for Gastric Tube Stenosis after Esophageal Cancer Resection]. AB - A 68-year-old man underwent esophagectomy for early esophageal cancer. Postoperative upper gastrointestinal series and esophagogastroduodenoscopy showed gastric tube stenosis. To improve passage, a removable self-expandable metallic stent (SEMS) was placed across the stenotic lesion. Two weeks later, the stent was removed, and passage through the gastric tube improved. The patient has no symptoms of stenosis. A removable SEMS could be an option for the treatment of gastric tube stenosis after esophagectomy. PMID- 26805217 TI - [Analysis of Esophageal Cancer Patients Undergoing Non-Curative Resection]. AB - The prognosis of esophageal cancer patients who undergo non-curative resection is very poor. Here, we retrospectively analyzed the factors associated with non curative resection. Thirty-five patients with cT3 or T4 thoracic esophageal cancer treated with neoadjuvant chemotherapy or chemoradiotherapy followed by esophageal resection were included in this study. Among the 35 patients, 27 underwent curative resection (R0 group), while 8 underwent non-curative resection (R1R2 group). A comparison of the clinicopathological factors between groups revealed no significant differences in presurgical factors. The pathological T factor was significantly deeper in the R1R2 group than in the R0 group (p=0.0086). Histopathological response tended to be higher in the R0 group (p=0.055). An accurate preoperative diagnosis of T factor is important. PMID- 26805218 TI - [A Case of Advanced Esophageal Cancer Patient with Schizophrenia Successfully Treated with Chemoradiation Therapy with S-1 and CDDP]. AB - A 67-year-old man who was hospitalized at a mental hospital because of schizophrenia was admitted to our hospital with a complaint of dysphagia and vomiting. He was found to have advanced cancer in the middle thoracic esophagus. With the cooperation of a radiologist, a psychiatrist, and a nurse, we successfully performed chemoradiation therapy with S-1 and CDDP. The patient had adverse events of esophagitis and anuria during chemoradiation therapy. However, such adverse events were well controlled through the cooperation with a palliative care team and a urologist. Finally, we were able to enforce chemoradiation therapy with S-1 and CDDP without interruption. PMID- 26805219 TI - [A Case of Lymph Node Metastases from Esophageal Cancer Successfully Treated with Weekly Paclitaxel Chemotherapy]. AB - A 61-year-old man underwent a curative operation for advanced esophageal cancer (CT-pT3N2M0, pStage III), which had been downstaged with docetaxel, CDDP, 5-FU (DCF) neoadjuvant chemotherapy. Five months after the operation, we diagnosed the patient with recurrence of esophageal cancer with para-aortic lymph node (PALN) metastasis. Systemic chemotherapy was initiated using a regimen of weekly paclitaxel (PTX) administration. After 2 courses, abdominal computed tomography examination indicated regression of the PALN swelling. Eighteen months have passed since the curative operation, and the patient has been doing well with no signs of recurrence. In summary, we successfully treated a case of lymph node metastases from esophageal cancer with weekly PTX chemotherapy. PMID- 26805220 TI - [Clinical Significance of Placing a PEG during Chemoradiotherapy for Advanced Esophageal Cancer]. AB - BACKGROUND: Unresectable advanced esophageal cancer is often treated with chemotherapy or chemoradiotherapy(CRT). Nutritional disorders caused by dysphagia may lead to a poor prognosis. Placing a PEG before starting CRT for advanced esophageal cancer may maintain better nutritional status. PURPOSE: The purpose of this study is to evaluate the clinical significance of placing a PEG before starting CRT for advanced esophageal cancer. RESULTS: Fifty-one cases were evaluated, 22 PEG (+) and 29 PEG (-). The rate of a CRT was better in PEG (+) than PEG (-) cases (91% vs 79%). Infection around the PEG was the only type of complication, affecting 5%. CONCLUSION: PEG feeding during CRT is important in the development of effective treatments for unresectable advanced esophageal cancer. PMID- 26805221 TI - [A Case of Esophageal Cancer with Paraaortic Lymph Node Metastasis Treated with Lymphadenectomy after Esophagectomy]. AB - A 70-year-old woman underwent subtotal esophagectomy with two-field lymph node dissection for squamous cell carcinoma of the middle thoracic esophagus (type 0- /IIa+IIc, pT1bN1 [2/25] M0, pStage II). Approximately 1 year and 2 months after surgery, abdominal CT showed a swollen paraaorticlymph node. PET-CT also indicated lymph node metastasis. The lymph node was diagnosed to have metastasis from the esophageal cancer, and the patient began treatment with chemotherapy. However, the treatment plan was changed to lymphadenectomy because of neutropenia. She underwent paraaortic lymph node dissection and right partial adrenalectomy. The lymph node was confirmed to have metastasis from the esophageal cancer. The neutropenia persisted after surgery, so she did not receive adjuvant chemotherapy. The patient remained alive for more than 5 years after surgery without any evidence of recurrence. Isolated paraaortic lymph node metastasis after esophagectomy is rare, and there have been only 2 cases, including our own, of long-term survival after paraaortic lymph node dissection. Lymphadenectomy for isolated lymph node metastasis can improve long-term prognosis but it cannot sufficiently predicate it. Therefore, accumulation of more cases is required. PMID- 26805222 TI - [A Case of Penetrating Diverticulum of the Small Intestine that Occurred during Chemotherapy for Esophageal Cancer]. AB - An 80-year-old man was seen by his family doctor with chief complaints of fatigue and loss of appetite. Upper gastrointestinal endoscopy showed a type 2 tumor of the lower thoracic esophagus, and the patient was referred to our hospital. Squamous cell carcinoma was diagnosed on biopsy, and computed tomography (CT) showed multiple pulmonary metastases. The patient was diagnosed with Stage IV thoracic esophageal carcinoma, and was started on combined chemotherapy with 5-FU plus CDDP. Seven days after the start of chemotherapy, the patient developed mild intermittent pain. By day 18, the blood tests showed a marked inflammatory response, and a CT scan showed an abscess in the small bowel mesentery. We suspected an intra-abdominal abscess caused by small bowel perforation, and performed a partial resection of the small bowel and abscess drainage. Postoperatively, pathology tests revealed a diagnosis of a small intestinal diverticulum, which had penetrated the mesentery. We report our experience of a rare case of penetrating diverticulum of the small intestine that occurred during chemotherapy for esophageal cancer, and review the literature. PMID- 26805224 TI - [A Case of Liposarcoma Occurring in the Retroperitoneum Treated by Laparoscopic Excision]. AB - We experienced a rare case of liposarcoma that we were able to remove laparoscopically based on a preoperative diagnosis. The patient in this case was a 67-year-old woman. Abdominal CT and pelvic MRI showed a mass of 15 cm in diameter on the left side of the pelvis. Well-differentiated liposarcoma was diagnosed based on these images. Based on imaging findings, the possibility of permeation to the neighboring organs was considered to be low, and so the operation was performed laparoscopically. The location of the tumor was similar to that seen during preoperative imaging diagnosis, and we were able to remove it laparoscopically without resecting the organ. The postoperative progress was good, and the patient left the hospital on the fourth postoperative day. This case shows how with detailed preoperative imaging, a minimally invasive approach is possible for the treatment of liposarcoma. PMID- 26805223 TI - [A Case of Retroperitoneal Lymphangioma that Was Difficult to Differentiate from Pancreatic Tumor]. AB - We report a rare case of retroperitoneal lymphangioma that was difficult to differentiate from pancreatic tumor. The patient was a 38-year-old woman. In June 2011, CT detected a pancreatic tail tumor. She was expected to undergo radical surgery and was referred to our hospital. The tumor was 55*43*40 mm in size and was described as a multilocular cystic lesion with a partition on CT. MRI demonstrated the tumor as a high-intensity area on T2-weighted images. Sonazoid enhanced US showed a contrast effect of the partition wall. Therefore, the lesion was diagnosed as a mucinous cystic neoplasm, and the patient underwent surgery. Intraoperatively, the tumor was a white multilocular cystic lesion with a capsule. The cystic lesion was exfoliated from the pancreatic parenchyma. Histologically, the tumor was diagnosed as a cavernous lymphangioma without malignancy. The surgery achieved good progress and the patient was discharged 12 days postoperatively. She is attending our clinic without any recurrence. PMID- 26805225 TI - [A Case in Which a Patient Was Operated for Intra-Abdominal Desmoid Tumors after Total Colectomy in FAP]. AB - The patient was a 22-year-old woman with FAP, who had undergone laparoscopic total colectomy 3 years previously. She presented to our hospital with a high fever and abdominal pain. Large hard tumors were palpated in the right lower abdomen and pelvis. Blood examination showed an inflammatory response. CT scan revealed 17 cm diameter solid tumors. At surgery, 2 tumors arising from the mesentery of the small intestine were found, neither of which invaded any organs. We performed tumor extirpation with partial resection of the duodenum, ileum, right fallopian tube and rectum. A jejunal stoma was formed, leaving a length of remnant intestine of about 120 cm. The histopathological diagnosis was given as desmoid tumor with infection. The patient was discharged from the hospital on the 9th postoperative day. Desmoid tumor is the second most common cause of death in FAP patients. Although desmoids can also occur in the extremities, most FAP patients develop intra-abdominal tumors. Despite being histologically benign, they are locally infiltrative and can cause death through invasion and destruction of adjacent vital structures and organs. Here, we report a case of desmoid tumors with FAP with reference to the literature. PMID- 26805226 TI - [A Case of a Desmoid Tumor the Developed Around Ileostomy in a Patient with FAP]. AB - A 21-year-old woman who underwent laparoscopic total colectomy for familial adenomatous polyposis (FAP) 1 year 3 months previously presented with a mass larger than 10 cm around the ileostomy. Multiple tumors in the mesentery around the ileostomy and anterior to the sacrum, accompanied by bilateral hydronephrosis, were detected by computed tomography. The patient was diagnosed with intraabdominal desmoid tumors, stage IV according to the Church's classification. The desmoid tumor (15*9 cm) around the ileostomy was completely resected surgically, whereas another desmoid tumor (5*4 cm) was incompletely resected. We found a desmoid tumor of more than 10 cm in size and many fibromatous plaques in the mesentery. We then performed 4 courses of systemic chemotherapy with dacarbazine and doxorubicin in for the residual desmoid tumors after surgery. There was no growth of the residual desmoid tumors for 12 months after chemotherapy. Genetic tests detected a pathogenic germline mutation of the APC gene in the high-risk region of the desmoid tumor. We also confirmed somatic mutations in the resected specimens. PMID- 26805227 TI - [A Case of Laparoscopic Gastrectomy for Gastric GIST after Neoadjuvant Chemotherapy with Imatinib Mesylate]. AB - We report the case of a 68-year-old woman who underwent laparoscopic gastrectomy for a gastric gastrointestinal stromal tumor (GIST) after neoadjuvant chemotherapy with imatinib mesylate. After conducting gastroscopy because of weight loss and anemia, we identified a submucosal tumor in the cardia. A GIST of 8 cm in diameter invaded the pancreatic tail and excluded the splenic vein. We administered imatinib 400 mg/day as neoadjuvant chemotherapy. We performed laparoscopic partial gastrectomy 5 months after the initiation of chemotherapy. According to the histopathological diagnosis, the surgical margin was positive. As an additional excision, we performed laparoscopic proximal gastrectomy. Without postoperative complications, it passes smoothly as of 5 months after surgery. PMID- 26805228 TI - [A Case of Intraductal Growth Pattern Gastrointestinal Stromal Tumor of the Stomach That Was Difficult to Diagnose by Biopsy]. AB - The patient, a 76-year-old man, presented to his local doctor's clinic with complaints of fatigue and lightheadedness. Because blood test results indicated anemia, he was referred to our hospital. Upper gastrointestinal endoscopy indicated a type 2 tumor of approximately 5 cm at the top of the gastric corpus. Biopsy results indicated that the lesion was a poorly differentiated adenocarcinoma. Computed tomography showed multiple liver metastases and the patient was diagnosed with stage IV gastric cancer. After a blood transfusion, chemotherapy with S-1 was started. However, as the patient experienced continued hemorrhage from the primary lesion, treatment was changed to total gastrectomy in order to control the bleeding. The pathologic examination of the resected specimen indicated that the tumor was located in the muscle and subserosal layers. The tumor cells were spindle-shaped, c-kit positive, cytokeratin negative, and Dog-1 positive. Therefore, a diagnosis of gastrointestinal stromal tumor (GIST) was made. Postoperatively, chemotherapy with imatinib was administered and the patient was alive with no progression of disease 1 year following surgery. Intraductal growth pattern GISTs of the stomach that protrude into the epithelium and exhibit ulceration can be difficult to distinguish from gastric carcinomas. We experienced a case of gastric GIST that was difficult to diagnose preoperatively. PMID- 26805230 TI - [A Case of Multiple Liver Metastases and Peritoneal Dissemination after Resection of a Gastrointestinal Stromal Tumor of the Stomach Successfully Treated with Imatinib Mesylate]. AB - A 71-year-old man was diagnosed with a gastric tumor approximately 50mm in diameter on computed tomography (CT). In January 2000, he underwent a proximal gastrectomy. Pathological examination showed 5 mitoses per 50 high-power fields, while immunohistochemical analysis showed positive staining for KIT. Accordingly, the tumor was diagnosed as an intermediate- risk malignant gastrointestinal stromal tumor (GIST) for which the patient was followed. In January 2002, an abdominal CT scan revealed multiple hepatic tumors and a lower abdominal tumor, and the patient was diagnosed with liver metastases and peritoneal disseminations from GIST. After informed consent was provided, chemotherapy with 400 mg/day imatinib was initiated. The patient demonstrated a partial response 2 months after treatment. At 12 years 8 months after the diagnosis of liver metastasis and peritoneal disseminations, the patient shows no sign of recurrence. PMID- 26805229 TI - [Intraluminal Type Gastrointestinal Stromal Tumor Resected by Single-Incision Percutaneous Endoscopic Intragastric Surgery--A Case Report]. AB - We report a patient with gastric gastrointestinal stromal tumor (GIST) who underwent single-incision percutaneous endoscopic intragastric surgery. The patient was a 70-year-old man. Esophagogastroduodenoscopy and abdominal computed tomography revealed the presence of an intraluminal type gastric submucosal tumor, 4 cm in diameter, in the posterior wall of the gastric body. Laparoscopic partial gastrectomy was performed via a single incision made in the epigastric region. The postoperative course was uneventful. The pathological diagnosis was a low-risk GIST. This method is easy and safe to perform; therefore, we consider it to be an important option for the treatment of intraluminal type gastric GIST. PMID- 26805231 TI - [A Case of Gastric Carcinoid Associated with Hypergastrinemia Treated with LATG]. AB - A 67-year-old man had a gastric polyp diagnosed on screening. Atrophic changes in the upper gastric mucosa were seen on upper gastrointestinal endoscopy. In addition, endoscopy revealed in the middle area of the stomach wall a 10 mm polyp that was diagnosed as a carcinoid tumor through biopsy. Blood serum gastrin was elevated at 2,800 pg/mL.We diagnosed a Rindi Type 1 gastric carcinoid. The patient was planned to be treated with surgical laparoscopy assisted distal gastrectomy (LADG); however, the procedure was changed to intraoperative laparoscopy assisted total gastrectomy (LATG). Chromogranin-positive tumor pathological findings in the mucous membrane submucosa and in the muscularis mucosae endocrine cell micronest (ECM) were widespread. There was no obvious vascular invasion. After the surgery, the serum gastrin level normalized and the patient remains alive. PMID- 26805232 TI - [Three Cases of Bleeding from Advanced Gastric Cancer Treated by Transcatheter Arterial Embolization(TAE)and Continued Chemotherapy]. AB - Case 1: A man in his 70s was underwent transcatheter arterial embolization (TAE) because of progressive anemia, and the gastroduodenal artery and left gastric artery were embolized. Two weeks later, he started chemotherapy (S-1, Tmab). Case 2: A man in his 60s was underwent TAE because of anemia. The left gastric artery and right gastroepiploic artery were embolized. Bleeding was controlled and he continued chemotherapy. Case 3: A man in his 70s was who vomited blood during the course of chemotherapy underwent TAE, during which contrast dye extravasated from the anterior gastric artery. The splenic artery was embolized. After TAE, abdominal pain and splenic infarction appeared, but could be treated by conservative therapy. Chemotherapy was started 4 weeks later. TAE is an effective method for controlling bleeding from advanced gastric cancer. PMID- 26805233 TI - [A Case of Granulocyte-Colony Stimulating Factor-Producing Gastric Cancer Successfully Treated with Trastuzumab]. AB - A 68-year-old man diagnosed with type 0-Igastric cancer by gastrointestinal endoscopy underwent urgent distal gastrectomy due to a perforation during endoscopic submucosal resection. Pathological examination revealed pT3N2M0, pStage IIIA. TS-1 was administered as adjuvant chemotherapy. Laboratory examinations 10 months after surgery revealed leukocytosis (19,100/mL). Positron emission tomography-CT demonstrated metastases in the bone marrow and ascending colon as well as around the liver. Chemotherapy using nab-PTX had poor efficacy and the leukocytosis worsened. Serum granulocyte- colony stimulating facto (r G CSF) was high at 1,640 pg/mL, and immunohistochemical staining was positive for G CSF. Thus, the patient was diagnosed with G-CSF-producing gastric cancer. The tumor was also positive for HER2 antibody by immunohistochemical staining. Combination therapy using TS-1 plus CDDP plus trastuzumab resulted in a good response, and the leukocytosis and elevated serum G-CSF gradually improved. The patient is living 30 months postoperatively and remains on chemotherapy. PMID- 26805234 TI - [A Case of a Submucosal Tumor-Like Gastric Cancer That Needed to Be Distinguished from Gastric Metastasis of Rectal Cancer]. AB - A 56-year-old man who underwent a radical operation and adjuvant chemotherapy for recurrent rectal cancer had been followed-up and had no recurrence for one and a half years. Thereafter, CT and upper endoscopy showed a submucosal tumor with a central recess developing in the stomach wall. It was suspected that the gastric tumor was either a metastasis of rectal cancer or a submucosal tumor-like gastric cancer. We performed a radical operation to remove the lesion. In the resected specimen, immunohistopathological findings including HER2 status suggested that the gastric tumor was a primary gastric cancer resembling a submucosal tumor. PMID- 26805235 TI - [A Case of Gastric Cancer Associated with Sjogren's Syndrome and Interstitial Pneumonia]. AB - A 77-year-old man presented with poor appetite and dyspnea. A gastroendoscopy showed an advanced gastric cancer and a CT scan demonstrated diffuse interstitial infiltrative shadows in both lungs. Laboratory data showed high level of anti-SSA and anti-SSB antibodies, suggestive of interstitial pneumonia associated with Sjogren's syndrome. Although the levels of KL-6 and SP-D, markers of interstitial pneumonia, decreased after steroid and immunosuppressive therapy, the CT findings of interstitial pneumonia showed no remarkable change. Surgery was performed 2 months after the administration of prednisolone since the respiratory function had improved, allowing the administration of general anesthesia. A CT scan revealed remarkable improvement of the lung lesions after the surgery. Therefore, it is likely that Sjogren's syndrome and interstitial pneumonia manifested as paraneoplastic syndromes in the presented case. PMID- 26805236 TI - [A Case of Gastric Cancer Associated with Membranous Glomerulonephritis]. AB - An 81-year-old woman was admitted for leg edema. She was found to have membranous glomerulonephritis with advanced gastric cancer after renal biopsy and endoscopic examination. Serum albumin was 1.4 g/dL and total protein was 4 g/dL on admission. After albumin was administered, distal gastrectomy was performed. Albumin administration continued post-operatively. The post-operative course was unremarkable and she was discharged on post-operative day 19. Six months after the operation, serum albumin gradually increased and uric protein volume decreased. Possible remission of membranous glomerulonephritis with gastric cancer can be expected after gastrectomy but careful perioperative management is required. PMID- 26805237 TI - [Thrombocytosis Associated with Poor Prognosis in Patients with Gastric Cancer]. AB - BACKGROUND: Thrombocytosis in patients with cancer is reportedly associated with an increased expression of angiogenic factors and a poor prognosis in some cancer types. The aim of this study was to analyze the clinicopathological significance and prognostic value of platelet counts in patients with gastric cancer. METHODS: Preoperative platelet counts were measured in 306 patients with gastric cancer who underwent surgery between 2001 and 2010.We used the cut-off level of 250.9*10(3) mL (mean) to define thrombocytosis and then analyzed the correlation between platelet count and clinicopathological factors. The multivariate prognostic value was determined using the Cox proportional hazards model. RESULTS: Platelet counts were significantly elevated in patients with lymph node metastasis (p=0.0349) and pStage IIIdisease (p=0.0326). Adjusting for venous invasion and pStage, multivariate analysis indicated that thrombocytosis as defined in this study was an independent prognostic factor (hazard ratio=1.50, 95%CI: 1.07-2.36, p=0.0402). CONCLUSION: A high platelet count is associated with tumor progression and poor survival in patients with gastric cancer. PMID- 26805238 TI - [Therapeutic Value of Lymphadenectomy and Prediction of Station No. 1 Lymph Node Metastasis in Lower-Third Gastric Cancers]. AB - BACKGROUND: According to the 14th Japanese Classification of Gastric Carcinoma(JCGC), station No. 1 lymphadenectomy for distal gastrectomy was included in the D1 level, though the 13th JCGC classified station No. 1 lymphadenectomy to the D2 level in patients with primary lower-third gastric cancer (LGC). This study was designed to re-evaluate the therapeutic value of lymphadenectomy, and to clarify the possible risk factors for station No. 1 lymph node metastasis (LNM) in LGC. METHODS: Between 1997 and 2014, 1,875 consecutive patients with gastric cancer underwent curative gastrectomy with radical lymphadenectomy. Of these, 344 patients who had a tumor located in the lower (L) or lower-duodenum (LD) area were analyzed retrospectively. RESULTS: 1) The therapeutic value of lymphadenectomy of stations No. 6, No. 3, No. 8a, No. 5, No. 4d, and No. 1 lymph nodes was proved to be higher than that of lymphadenectomy of other station lymph nodes. Patients with station No. 1 LNM had a significantly higher incidence of undifferentiated type, lymphatic invasion, venous invasion, and pT2-4 tumor. 2) Regarding factors to predict station No. 1 LNM in LGC, there was no station No. 1 LNM in patients with both early and differentiated type LGC. Distance from the pylorus to the tumor center (DPT) significantly correlated with station No. 1 LNM. Particularly, there was no station No. 1 LNM in patients with early LGC and DPT<50 mm. CONCLUSIONS: In patients with early and differentiated type LGC and DPT<50 mm, limited surgery to omit station No. 1 lymphadenectomy might be possible. PMID- 26805239 TI - [Clinical Risk Factors and Problems Associated with the Difference between Preoperative and Pathological Diagnosis of Tumor Depth in Patients with Upper Third Gastric Cancer]. AB - BACKGROUND AND AIMS: The epidemiology of gastric cancer is changing with an increasing proportion of tumors in the upper stomach. This study was designed to identify risk factors and clinical problems related to the difference between clinical and pathological diagnosis of tumor depth in cases of upper third gastric cancer. PATIENTS AND METHODS: A total of 119 consecutive patients with upper third gastric cancer, who underwent curative gastrectomy between 2008 and 2012, were retrospectively analyzed. RESULTS: The patients were divided into 2 groups based on the pattern of the difference between the clinical (c) and pathological (p) diagnosis of the T factor. Thirty patients (25%) were included in the underestimated diagnosis group (UE group, cTpT or cT=pT). The number of cases showing undifferentiated type (TMN) and lymphatic invasion was significantly higher in the UE group compared to the OC group. Multivariate analysis revealed that the undifferentiated type (TMN) was an independent risk factor for underestimation (p<0.05). CONCLUSION: The presence of undifferentiated components in upper third gastric cancer was associated with a high incidence of underestimated diagnosis. Care should be taken in decision making for surgical treatments based on the clinical diagnosis. PMID- 26805240 TI - [A Case of Advanced Gastric Cancer with Synchronous Liver Metastases Treated with Combination Therapy]. AB - A 66-year-old woman was admitted to our hospital because of epigastralgia, and she was diagnosed with a type 2 tumor at the antrum of the stomach. Pathological examination suggested a moderately differentiated adenocarcinoma with negative staining for HER2 on immunohistochemistry. Abdominal CT showed gastric wall thickening and enlarged lymph nodes. Although the clinical finding was Stage IIIB(T4aN2M0), a liver metastasis (S2) was found during the operation. We performed distal gastrectomy with D2 lymph node dissection and partial hepatic resection in December 2010. A post-operative pathological diagnosis of gastric cancer, pT4aN2M1, pStage IV, was made. Although adjuvant chemotherapy of S-1 was administered, CT revealed a liver metastasis in S3 5 months after the operation, and the patient underwent transcatheter arterial chemoembolization (TACE) followed by a regimen of S-1 plus CPT-11. After 3 courses of this regimen, grade 2 anorexia was observed, and the treatment schedule was changed to a regimen of capecitabine plus cisplatin (XP). After 7 courses of this regimen, CT revealed multiple liver metastases in S2, S3, and S8, and the treatment schedule was changed to several other chemotherapy regimens. However, liver metastases continued to grow, and the patient died 51 months after surgery. Although the prognosis of gastric cancer with synchronous liver metastases is very poor, it is possible to prolong survival with multimodal therapy. PMID- 26805241 TI - [A Case Report--A Synchronous Liver Metastasis from Gastric Cancer Treated with Chemotherapy, Surgical Resection of the Gastric Cancer, and RFA of the Liver Metastasis]. AB - A 71-year-old man was admitted to our hospital because of abdominal pain. An upper gastrointestinal endoscopy revealed a type 3 tumor in the lesser curvature of the gastric body. A computed tomography (CT) scan showed synchronous liver metastasis in liver S6 and S8, and a large 8a lymph node that could be encased within the common hepatic artery. The patient was diagnosed with gastric cancer with liver metastasis, Stage IV, and treated with chemotherapy (S-1 plus CDDP). After 3 courses, a CT scan showed that the liver metastasis in S8 was reduced in size.The one in S6 completely disappeared. The 8a lymph node was also reduced in size and revealed to be separated from the common hepatic artery. Total gastrectomy (D2) and radiofrequency ablation (RFA) for the S8 lesion were performed. The postoperative course was favorable and the patient was treated with postoperative adjuvant chemotherapy consisting of S-1. No recurrence has been observed for 17 months after diagnosis. After chemotherapy, if R0 resection is performed, surgical resection and RFA for liver metastasis may be a useful option for gastric cancer with liver metastasis. PMID- 26805242 TI - [A Case of Successful Treatment of Metachronous Liver Metastasis from Gastric Cancer with Hepatectomy]. AB - A 77-year-old man was found to have advanced gastric cancer and underwent total gastrectomy (pT4aN2H0P0M0, Stage IIIB). Two years after gastrectomy, we found an elevated tumor marker level, and a liver metastasis appeared in segment 5 (20 mm in diameter). He was treated with S-1/CDDP combination chemotherapy. After 2 courses of chemotherapy, the tumor marker level kept rising and a CT scan detected a progressive tumor. S-1/irinotecan combination chemotherapy was administered as second-line chemotherapy. After 6 courses of chemotherapy, the size of the liver metastasis was reduced and the tumor marker level normalized. Because lymph node metastasis or peritoneal recurrence was observed, a partial resection of the liver (S5) was performed. After the operation, he was treated with S-1 chemotherapy again for 1 year and has had no recurrence. PMID- 26805244 TI - [A Case of Long-Term Survival of a Patient with Gastric Cancer with Peritoneal Dissemination]. AB - The patient was a 75-year-old man with a history of gastrectomy with combined resection of the transverse colon ligament for gastric cancer in July 2011. He was diagnosed with adenocarcinoma (tub2, tub1), L, Ant-Gre, type 2, pT4b (SI: transverse colon ligament) and pN3b, H0, M0, P0, CY0, Stage IIIC. On abdominal computed tomography 7 months after surgery a peritoneal metastasis was seen near the transverse colon. The patient was treated with resection for peritoneal dissemination with part of the transverse colon. Three years after the last surgery, the patient is still alive without relapse. PMID- 26805243 TI - [A Long Surviving Case of Resected Advanced Gastric Cancer with a Synchronous Adrenal Metastasis]. AB - We report a long surviving case of gastric cancer with a synchronous adrenal metastasis in a patient who underwent curative resection. The patient was a 74 year-old man. Endoscopic examination revealed a type 3 gastric cancer in the proximal stomach. Abdominal computed tomography (CT) revealed a soft tissue density mass in the right adrenal gland and a high-density mass suspected as hemangioma in the left adrenal gland. The CT scan indicated no other distant metastasis. The patient had no endocrine abnormalities according to blood test results. Total gastrectomy with D2 lymphadenectomy and right adrenalectomy were performed in August 2003. On histopathological examination, the gastric tumor was diagnosed as a poorly differentiated adenocarcinoma. The histopathological findings of the right adrenal tumor were compatible with those of gastric cancer. The final diagnosis was por1, 105*65 mm, pT2 (SS), pN1 (#1: 2/8, #3: 1/11), P0, H0, CY0, pM1 (ADR), pStage IV. Two months after the surgery, the patient was treated with adjuvant TS-1 monotherapy (80 mg/m2 day 1-28/q6w) for 1 year 9 months. The patient had been in good health without a recurrence for more than 9 years 3 months after the operation. PMID- 26805245 TI - [A Case of Double Cancers of the Stomach and Endometrium with Peritoneal Metastasis]. AB - The patient was a 59-year-old woman with advanced double cancers of the stomach and endometrium with peritoneal metastasis. Abdominal computed tomography revealed that the endometrial cancer was more advanced than the gastric cancer; therefore, the peritoneal metastasis was diagnosed as arising from the endometrial cancer. Treatment of the endometrial cancer with cytoreductive surgery followed by adjuvant chemotherapy was performed first. She underwent total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. Disseminated nodules were found throughout her abdomen. The histopathological findings indicated carcinosarcoma of the uterus, pT3bNXM1, Stage IVb. One month after surgery, she received 6 courses of adjuvant chemotherapy with paclitaxel plus carboplatin. After the adjuvant chemotherapy, abdominal computed tomography revealed that both the ascites and the disseminated nodules had disappeared. Therefore, a second-look surgery for the endometrial cancer and definitive surgery for the gastric cancer were planned. At the laparotomy, no disseminated nodules were found, so distal gastrectomy and D2 lymphadenectomy were performed. The histopathological findings were pT4aN1M0P0Cy0, Stage IIIA. She received adjuvant chemotherapy with S-1 for 1 year, and has been alive with no evidence of recurrence for 2 years and 7 months after the initial surgery. PMID- 26805246 TI - [A Case of Long-Term Survival after Surgeries for Gastric Cancer and Metachronous Ovarian Metastasis]. AB - The patient was a 57-year-old woman. In October 2011, she underwent distal gastrectomy, D2 lymphadenectomy, and Roux-en-Y reconstruction for gastric cancer (pT4a, pN3b, Stage IIIC [JCGC 14th Edition]). She then received S-1 plus CDDP combination therapy and S-1 monotherapy as postoperative adjuvant chemotherapies for 1 year, and was followed up as an outpatient. In April 2013, a significant increase in the CA19-9 level was noted, and CT indicated a right ovarian tumor. Ovarian metastasis from the gastric cancer was diagnosed, and the response to 3 courses of weekly PTX was stable disease. No findings indicated metastasis to other organs. In July 2013, a salpingo-oophorectomy was performed, after which her CA19-9 level returned to the normal range. Follow-up was adopted as the postoperative strategy in part due to the desires of the patient. Presently, 3 years and 6 months after the initial surgery and 1 year and 9 months after the last surgery, no recurrence has been detected. Generally, ovarian metastasis from gastric cancer is considered to be associated with a poor prognosis. However, our patient showed long-term survival after surgeries for gastric cancer and asynchronous ovarian metastasis. Here, we report the details of our case and review the relevant literature. PMID- 26805247 TI - [Multidisciplinary Therapy for Advanced Gastric Cancer with Liver and Brain Metastases]. AB - A 68-year-old man was admitted to our hospital. He was diagnosed with advanced gastric cancer with multiple liver metastases. The primary tumor was treated with distal gastrectomy with D2 dissection and anti-cancer agents, and then he was scheduled for a 2-stage hepatic resection. After surgery, the liver metastases disappeared, and he was diagnosed with a CR. However he complained of dizziness and was diagnosed with metachronous brain matastasis. Multidisciplinary treatment including resection and radiotherapy was administerd and he survived for 5 years after diagnosis. PMID- 26805248 TI - [Inventive Approach during Laparoscopic Distal Gastrectomy for Treatment of Gastric Cancer in Patients with Adachi Type VI Vascular Anomaly]. AB - Vascular anomalies, as described by the Adachi classification, are an inevitable issue for gastric cancer surgery. Here, we report a safe technique for laparoscopic lymph node dissection in a patient with Adachi typeVI vascular anomaly. The patient is a 72-year-old woman, who presented with a submucosal gastric cancer located on the lesser curvature of the stomach. Preoperative MDCT revealed Adachi type VI vascular anomaly. At laparoscopic surgery, we first identified the portal vein. Then, dissection of the hepatoduodenal and No. 8a lymph nodes was performed from the location near the portal vein at the superior portion of the hepatoduodenal ligament to that near the splenic vein superior to the pancreas. This avoids the disorientation that may result from anomalous vessels and prevents error that can lead to vascular complications. Subsequently, she underwent D1 plus gastrectomy. Her postoperative course was uneventful. Our surgical technique offers a safe approach for laparoscopic gastrectomy in the patient with Adachi type VI vascular anomaly. PMID- 26805249 TI - [A Case of Laparoscopic Gastrectomy in a Patient with Refractory Vasospastic Angina]. AB - We report a case of laparoscopic gastrectomy in a patient with refractory vasospastic angina. An 83-year-old man received 2 types of oral coronary vasodilators but complained of chest pain about twice a week thereafter. He was diagnosed with refractory vasospastic angina. Upper gastrointestinal endoscopy was performed for tarry stools and revealed a type 2 tumor in the anglar posterior wall. CT revealed no lymph node swelling or metastasis. Laparoscopic gastrectomy was performed, and intravenous administration of coronary vasodilators was started before the operation. During the operation, coronary spasm could be prevented while being careful not to induce circulation change, bleeding, or traction of the peritoneum. Many cases of coronary spasm-related angina in the absence of a history of angina have been reported during non cardiac operations. In such cases, careful coronary spasm is necessary. PMID- 26805250 TI - [A Case of Long-Term Survival after Pancreatoduodenectomy for Gastric Cancer with Pancreatic Invasion]. AB - A 79-year-old woman with symptomatic pyloric stenosis was diagnosed with advanced gastric cancer. CT revealed that the tumor had invaded into the pancreatic head.Since no contraindications were found at laparotomy, we performed pancreatoduodenectomy. The histopathologic diagnosis was pT4b (panc), pN3a (11/35), P0, CY0, H0, M0, pStage IIIC, R0. The patient received adjuvant chemotherapy with S-1 for 1 year. The patient has survived without recurrence for more than 2 years. The efficacy of pancreatoduodenectomy for advanced gastric cancer is still controversial. Pancreatoduodenetomy may be indicated for selected cases of advanced gastric cancer, if an R0 resection can be achieved. PMID- 26805251 TI - [Treatment Strategy for Gastric Carcinoma with Lymphoid Stroma]. AB - Gastric carcinoma with lymphoid stroma (GCLS) is a histological type with severe lymphocytic infiltration. GCLS is very rare and few cases have been reported. We examined the clinical features, problems of preoperative diagnosis, and treatment of 14 cases (1.8%) that were diagnosed as GCLS out of 790 gastric cancers surgically resected in our hospital. The mean age was 69 years. Six, 8, and 0 cases were located in the upper, middle, and lower fields of the stomach, respectively, and 8, 1, 4, and 1 cases were macroscopically 0-IIc, 0-I, type 2, and type 3, respectively. The depth of invasion was M, SM1, SM2, MP, and SS in 0, 0, 9, 3, and 2 cases, respectively. There were 12 cases(86%)with infection by Epstein-Barr virus, and just 1 case with lymph node metastasis. All cases have had no evidence of recurrence. There were no cases that were diagnosed as GCLS before surgery. GCLS is recognized as having a more favorable prognosis compared with other types of gastric carcinoma, so an aggressive surgery might achieve good outcomes. However, preoperative diagnosis is very difficult and there is a compelling need for new techniques or criteria for diagnosis of GCLS. PMID- 26805252 TI - [A Case of Gastritis Cystica Polyposa That Developed Early after Distal Gastrectomy]. AB - We present a case of gastritis cystica polyposa (GCP) that developed early after laparoscopy-assisted distal gastrectomy with BillrothIreconstruction. GCP is a chronic inflammatory gastric mucosal lesion that emerges at an anastomotic site usually after a long post-gastrectomy period, which is mainly caused by constant chemical stimulation by duodenal juice. In addition, chronic mechanical stimulation caused by reflux or stasis of gastrointestinal contents may also trigger GCP. Surgeons should ensure a functional and physiologically patent anastomosis during surgery. Hypergastrinemia, caused by persistent Helicobacter pylori infection or continuing administration of proton pump inhibitors, may also contribute to the development of GCP, as GCP is a type of hyperplastic polyp. Therefore, appropriate postoperative follow-up, including pylorus eradication and avoidance of unnecessary administration of proton pump inhibitors, seems to be needed in order to prevent the development of GCP. In our case, many factors exhibited the multiplier effect, resulting in early development of GCP. As GCP also attracts much attention as a precancerous lesion, appropriate prevention and prompt treatment are required. PMID- 26805253 TI - [A Case of Acute Afferent Loop Obstruction after Total Gastrectomy, Successfully Managed by Endoscopic Treatment]. AB - The patient was a 76-year-old man who had 3 times previously undergone laparotomies, including distal gastrectomy with a Billroth I operation. In the current case, a total gastrectomy, end-to-side esophagojejunostomy, and a Roux-en Y anastomosis for adenocarcinoma of the remnant stomach were performed. On postoperative day (POD) 7, he complained of epigastralgia. Abdominal CT revealed a markedly dilated duodenum, and a diagnosis of acute afferent loop obstruction was made. Emergency endoscopy revealed edematous stenosis of the Y-anastomotic site. A nasal endoscope could not pass the stricture, but an endoscopic nasobiliary drainage (ENBD) catheter was successfully inserted into the duodenum. Epigastralgia decreased after drainage. Stenosis of the Y-anastomotic site was still observed 18 days after onset; therefore, we inserted 1 endoscopic retrograde biliary drainage (ERBD) tube, in addition to the ENBD catheter. Twenty five days after onset, slight improvement of the stenosis was observed. By inserting 2 more ERBD tubes, the ENBD catheter could be removed. On day 28, abdominal CT revealed reduced dilatation of the duodenum. On day 29, oral intake was initiated, and the patient was discharged from the hospital on POD 66. During the early post-operative phase, the use of nasal endoscope drainage is an effective, minimally invasive, and safe procedure for decompression of the duodenum in afferent loop obstruction. PMID- 26805254 TI - [Interventional Radiology for Intra-Abdominal Abscess after Gastrectomy]. AB - Approximately 20% of patients develop some complications after gastrectomy. These complications should be treated appropriately to achieve a positive outcome. The records of 6 patients with postoperative intra-abdominal abscesses treated with interventional radiology (IVR) were analyzed. The cause of abscess was anastomotic leakage in 4 patients and contaminated surgery after gastric perforation in 2 patients. Intra-abdominal abscesses were detected on postoperative day 12 (median), and an IVR-guided drainage tube was inserted with a median interval of 1 day. The drainage tube was kept in place for 26 days (median), and patients were discharged 6.5 days (median) after drainage tube removal. No patients were converted to open surgery. Early IVR-guided drainage was essential and effective for intra-abdominal abscess treatment after gastrectomy. PMID- 26805255 TI - [A Case of Strangulation Ileus with Hemorrhagic Shock Caused by an Internal Hernia of the Small Intestine]. AB - PATIENT: An 81-year-old man. Past medical history: distal gastrectomy and Roux-en Y reconstruction. CHIEF COMPLAINT: epigastric pain, nausea, and hematemesis. History of present illness: the man developed epigastric pain, nausea, and hematemesis the day before visiting our hospital. Upper gastrointestinal endoscopy revealed that the small intestinal mucosa was extensively congested, and a clinical condition due to the previous gastric surgery was suspected. Therefore, the man was admitted to our department. The patient was diagnosed with strangulation ileus by contrast-enhanced abdominal CT, and was referred for emergency surgery. At the time of entering the operating room 3 hours later, his abdomen was remarkably swollen. After anesthesia induction, his blood pressure dropped to 40-49 mmHg, and he was in a state of shock. Strangulation ileus was caused by an internal hernia of the small intestine through the gap between the mesenteric sutures of the Roux-en-Y reconstruction. The small intestinal wall was significantly discolored and remarkably expanded due to bleeding into the small intestine. We determined that mass resection of the small intestine posed high risk, and performed only reduction of the small intestinal hernia. Since strangulated ileus causing hemorrhagic shock is rare, we describe the case and review the literature on the topic. PMID- 26805256 TI - [Laparoscopic Gastrostomy for a Patient with Wernicke's Encephalopathy after Gastrectomy--A Case Report with a Literature Review]. AB - Wernicke's encephalopathy is usually related to alcoholism, malnutrition, or hyperemesis gravidarum. We report a case of Wernicke's encephalopathy after distal gastrectomy for gastric cancer. A 58-year-old man underwent distal gastrectomy with Billroth Ireconstruction for early gastric cancer. Nine months later, he developed anorexia and vomiting for a few days. Brain MRI showed no significant findings, and he resumed ingestion 5 days after admission. On the 8th day of hospitalization, dysphagia suddenly developed and brain MRI indicated Wernicke's encephalopathy. Vitamin B1 was immediately injected, and neurological symptoms gradually improved. However, dysphagia did not adequately improve, leading to severe aspiration pneumonitis. Laparoscopic gastrostomy was performed for aspiration of the stomach contents and initiation of enteral nutrition. After gastrostomy, the patient made good progress and was transferred to a rehabilitation hospital. We should recognize that gastrectomy can cause Wernicke's encephalopathy. PMID- 26805257 TI - [A Case of Locally Advanced Gastric Cancer after Neoadjuvant Chemotherapy]. AB - A 60s male was admitted to our hospital because of appetite loss and nausea. After examination, he was diagnosed with type 3 advanced gastric cancer in the antrum. Abdominal computed tomography showed gastric cancer invasion to the left liver lobe. We initiated neoadjuvant chemotherapy using S-1 plus CDDP after laparoscopic gastrojejunostomy. S-1 was orally administered for 3 weeks followed by a 2-week drug-free period. CDDP was administered intravenously on day 8 of each course. After 5 courses of chemotherapy, the gastric cancer was reduced in size. We therefore performed total gastrectomy with D2-affiliated left liver resection. S-1 plus CDDP is expected to improve outcomes in unresectable or locally advanced gastric cancer. PMID- 26805258 TI - [A Case of HER2-Positive Advanced Gastric Cancer with a Pathological Complete Response to Neoadjuvant Chemotherapy with S-1/CDDP/Trastuzumab]. AB - A 61-year-old man was referred to our hospital because of epigastric pain. Upper gastrointestinal endoscopy revealed a type 2 tumor at the gastric antrum, which was diagnosed as gastric adenocarcinoma (tub1) by pathological examination and was HER2 positive 3+ by the IHC method. Abdominal computed tomography revealed multiple metastases to regional lymph nodes (LNs), including bulky nodes at No. 3, 6, and 11p stations. In particular, No. 6 LN was 43 mm in diameter and had invaded to the pancreas. The clinical stage was IIIc (T4aN3M0) and neoadjuvant chemotherapy was conducted using S-1/CDDP/trastuzumab. After 2 cycles of chemotherapy, a partial clinical response was obtained and distal gastrectomy with LN dissection (D2 plus No. 16 LN) was performed. The pathological specimens showed no residual cancer cells in the stomach and LNs (Grade 3: pCR). Adjuvant chemotherapy was not administered. The patient is alive 10 months after the surgery with no evidence of recurrence. PMID- 26805259 TI - [A Case of Resected Advanced Gastric Cancer Exhibiting Pathological Complete Response after Neoadjuvant Che-motherapy(DTX/CDDP/S-1:DCS)]. AB - A 71-year-old man was diagnosed with gastric cancer (LM, Less, type 2, T4aN2M0, cStageIIIb). A diagnostic laparoscopic surgery revealed serosal invasion without peritoneal dissemination. Two courses of neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer using DCS (DTX: 20 mg/m2 on day 1, CDDP: 50 mg/m2 on day 1, S-1: 120 mg/day, twice a day on days 1-14) was performed, which resulted in a clinical partial response. Consequently, distal gastrectomy with D2 lymph node dissection, and BillrothIreconstruction were carried out. Histopathological examination revealed no residual cancer cells both in the primary lesion and in the lymph nodes, indicating a pathological complete response (grade 3). Six courses of S-1 (120 mg/day on days 1-28, followed by 2 weeks of rest) were administered as adjuvant chemotherapy. At the 2 years 10 months follow-up after adjuvant therapy, the patient has had no recurrence. Combination chemotherapy with NAC-DCS can be a safe and effective regimen for locally advanced gastric cancer. PMID- 26805260 TI - [A Case of Advanced Gastric Cancer Responding to Neoadjuvant Docetaxel/CDDP/S-1 Therapy with Metallic Stent Placement, Leading to Curative Surgery]. AB - A 59-year-old man presented with epigastralgia. A diagnosis of advanced gastric cancer MLU, Circ, Type 3, 160 mm, tub2, cT4b (SI: panc), cN1, cM0, cH0, cP0, cCY0, cStage IIIB was made. Because of difficulty with oral intake due to malignant outlet obstruction and tumor bleeding, endoscopic self-expanding metallic stent placement was performed. We administered chemotherapy involving docetaxel, cisplatin, and S-1(DCS). After 2 courses of chemotherapy, the primary lesion and regional lymph nodes had reduced in size. His response was judged as SD according to the RECIST criteria. The patient elected to undergo explorative laparotomy for assessment of the gastric cancer. The intraoperative findings showed that there was no pancreatic invasion, peritoneal dissemination, or distal metastasis, so a total gastrectomy and D2 lymph node dissection was performed. The pathological findings showed that there were very few cancer cells in the primary lesion, and a lymph node metastasis was found. The final stage was gastric cancer MLU, Circ, Type 3, 100 mm, muc, ypT4a(SE), ypN3a (13/51), ypM0, ypH0, ypP0, ypCY0, ypStage IIIC. The therapy evaluation was Grade 1b. In summary, we encountered a patient with gastric cancer in whom curative surgery was made possible by undergoing chemotherapy and metallic stent placement. PMID- 26805261 TI - [A Case of Advanced Gastric Cancer with Peritoneal Dissemination Effectively Treated with S-1 and Docetaxel Combination Chemotherapy]. AB - A 72-year-old man underwent surgery for advanced gastric cancer. Systemic chemotherapy was started, using a regimen of S-1/CDDP for 4 courses, followed by 8 courses of S-1. Three years and 8 months after the surgery, abdominal CT demonstrated ascites, and the serum CA19-9 level was abnormally high (1,165.1 U/mL). Adenocarcinoma cells were found in the ascites. Treatment with S 1/docetaxel (DOC) was started. After 10 courses, the ascites disappeared and the serum CA19-9 value returned to normal. Four years and 7 months after the operation, the patient has been in good health, with no signs of recurrence. PMID- 26805262 TI - [Long-Term Disease-Free Survival through Postoperative Chemotherapy in a Case of Gastric Cancer with Peritoneal Dissemination]. AB - An 80-year-old man with type 4 gastric cancer in the mid-gastric region underwent total gastrectomy and D2-No.10 lymph-node dissection (cT4a, N0, M0, cStageIIB). Several nodules were detected under the left diaphragm, some of which were biopsied. Pathological findings indicated a poorly differentiated adenocarcinoma, pT4a (SE), pN3b, pM1 (P1, CY1), pStage IV. Systemic chemotherapy was initiated, using a regimen of S-1/docetaxel (DOC). After 6 courses of combination therapy, we switched to S-1 alone, which was continued for 1 year. Eighteen months after the surgery the patient discontinued S-1 treatment and has since survived for 5 years with no obvious cancer recurrence. PMID- 26805263 TI - [Introduction of Chemotherapy for Advanced Gastric Cancer Showing Oncologic Emergency Caused by Peritoneal Dissemination--Report of Tow Cases]. AB - Here, we report 2 patients with gastric cancer and peritoneal dissemination who were successfully treated with chemotherapy after undergoing treatment for an oncologic emergency caused by peritoneal dissemination. Case 1 involved obstruction of the sigmoid colon caused by peritoneal dissemination. After urgent colostomy, S-1/IP IV paclitaxel chemotherapy was introduced. The patient continued the therapy for 2 years and 2 months. Case 2 involved acute renal failure due to bilateral ureter obstruction and obstructive jaundice caused by peritoneal dissemination. This patient underwent emergency treatment consisting of Double-J ureteral stent insertion and endoscopic nasobiliary drainage. He was successfully started on chemotherapy with S-1/oxaliplatin/IP paclitaxel. He continued the therapy for 8 months without symptoms. Aggressive treatment might be effective for advanced gastric cancer showing oncologic emergency. PMID- 26805264 TI - [A Case of Advanced Gastric Cancer with Long-Term Survival after Chemotherapy with Combined S-1 and CPT-11]. AB - Here, we report a 54-year-old man diagnosed with type 3 advanced gastric cancer who underwent a total gastrectomy and splenectomy plus D2 lymphadenectomy. The pathologic diagnosis was Stage IV (T3N0H0P0CY1M1). Sixteen courses of combined S 1/CPT-11 chemotherapy were completed, at which time the CPT-11 was discontinued because of malaise, and S-1 alone was continued for a year. The patient is well and has been recurrence-free for 7 years. Thus, he is considered a long- term survivor who was treated with combination S-1/CPT-11 chemotherapy. PMID- 26805266 TI - [A Case of Conversion Surgery after Long-Term Chemotherapy for Advanced Gastric Carcinoma with Synchronous Distant Metastasis]. AB - We report the case of a patient who underwent conversion surgery after long-term chemotherapy for advanced gastric carcinoma with synchronous distant metastasis. She was admitted to our hospital because of back pain and elevated serum ALP level. Gastrointestinal endoscopy showed multiple 0-IIa like lesions at the gastric antrum, and a biopsy specimen showed poorly differentiated adenocarcinoma negative for HER2. Colonoscopy showed a submucosal tumor at the cecum, and pathological examination revealed metastatic gastric adenocarcinoma. CT revealed regional lymph node metastasis, bilateral ovarian tumors, and systemic bone absorption indicating metastasis. Systemic chemotherapy with cisplatin and S-1 was carried out, and complete resolution of gastric and colic lesions was obtained. Afterwards, a new gastric lesion appeared with re-growth of regional lymph nodes and bilateral ovarian tumors. Distal gastrectomy with D2 dissection and bilateral ovariectomy was performed 2 years 6 months after the initial therapy. Although systemic chemotherapy is the standard treatment for advanced gastric carcinoma with distant metastasis, surgical resection can be justified when drug-resistant lesions are localized and conversion surgery is feasible. Postoperative chemotherapy is mandatory to prolong survival. PMID- 26805265 TI - [Long-Term Survival of Gastric Cancer with Peritoneal Metastasis--A Case Report]. AB - We report a case of almost 9-year survival of a patient with unresected gastric cancer with peritoneal metastasis. A 76-year-old Japanese man was admitted to the hospital for resection of gastric cancer, but it was not resected because of peritoneal metastasis. After discharge, the patient was treated with combination chemotherapy of S-1 and paclitaxel (PTX). After 8 cycles of chemotherapy, the tumor disappeared. We recommended surgical therapy, but he did not agree. The chemotherapy was continued for almost 9 years with 8 regimens including S-1 plus PTX (21+8+5 cycles), S-1 plus CPT-11 (11+2 cycles), S-1 plus docetaxel (DOC) (25 cycles), S-1 plus CDDP plus trastuzumab (1 cycle), PTX (5 cycles), PTX plus trastuzumab (1 cycle), DOC (6 cycles), and nab-PTX (1 cycle). With nutrition support provided through an enterocutaneous fistula and home parenteral nutrition, he has taken chemotherapy throughout without severe complications. PMID- 26805267 TI - [A Case Report of Advanced Gastric Cancer Demonstrating CR after Treatment with S 1 and Paclitaxel]. AB - Here, we report a case of advanced gastric cancer that demonstrated CR after treatment with S-1 and paclitaxel. The patient was an 80-year-old woman with gastric cancer in whom upper gastrointestinal endoscopy (GIF) revealed a type 3 tumor in the cardia of the stomach that was pathologically diagnosed as a well differentiated adenocarcinoma. Computed tomography showed no lymph node involvement or metastasis. Considering her advanced age and cardinal functional disorder, she was administered chemotherapy consisting of S-1 and paclitaxel. Depending on a state, a side effect, I changed a dose and inter-dose interval from head to foot and I treated it by foreign going to hospital and continued it. Gradual tumor reduction was observed on GIF (2011/1/25). CR was diagnosed without tumor disappearance, with accepted malignant findings on biopsy. The patient has now survived for 7 years 9 months after diagnosis. The present case demonstrates that combination therapy of S-1 and paclitaxel is safe and useful for patients with risk factors such as advanced age and underlying disease. PMID- 26805268 TI - [A Case of Advanced Gastric Cancer for Which Curative Resection Was Performed, Despite CEA Elevation]. AB - A 32-year-old man was admitted to our hospital with the complaint of epigastric pain. Gastrointestinal endoscopy revealed a type 5 advanced gastric cancer at the posterior wall of the antrum. Contrast-enhanced computed tomography (CT) and endoscopic ultrasonography showed a fluid collection, indicating peritoneal metastasis. CEA levels were elevated, at 16.5 ng/mL. A diagnosis was made of cStage IV (T4aN3H0P1M1), and he underwent first-line chemotherapy using CDDP and S-1. However, this immediately failed with the severe adverse effect of vomiting.Docetaxel and S-1 were adopted as second-line chemotherapy. Since progression of the disease was confirmed after 8 cycles of second-line chemotherapy, nab-paclitaxel was administered as third-line chemotherapy. Despite a trend of increasing CEA after 4 cycles of third-line chemotherapy, CT revealed a tumor volume reduction as well as the disappearance of the fluid collection, after which staging laparoscopy was performed. Based on the finding that non curative factors such as fluid collection and peritoneal nodules were not observed, distal gastrectomy was performed. Histopathological examination showed a ypStage IA (T1bN0H0P0M0)tumor with a grade 3 therapeutic response to chemotherapy.The patient is currently doing well with no recurrence 11 months after the operation. PMID- 26805269 TI - [A Case of Recurrent Gastric Cancer with Left Cervical Lymph Node and Para-Aortic Lymph Node Successfully Treated with TS-1 Chemotherapy]. AB - We report a case of recurrent gastric cancer with left cervical and para-aortic lymph node close to the hilum of the right kidney that was successfully treated with TS-1 monotherapy and surgical resection. The patient was a 55-year-old woman. She underwent total gastrectomy with D2 lymphadenectomy for gastric cancer in June 2002. Histopathological examination revealed type 4, por1, pT3 (SE), pN1 (#4d: 1/5), H0, P0, M0, CY0, pStageIIIA. She refused to receive adjuvant chemotherapy. At 1 year 7 months after gastrectomy, she noticed cervical lymph node swelling. Computed tomography (CT) revealed a 2.5 cm diameter lymph node. Histopathological examination of an aspiration needle biopsy specimen from the left cervical lymph node confirmed that the tumors had metastasized from gastric cancer. Treatment with TS-1 (120 mg/day) was initiated in January 2004 and continued for 2 years 5 months. A complete response was achieved 5 months after treatment initiation and continued until the present. Abdominal CT revealed a para-aortic lymph node that tended to increase in size. Positron emission tomography revealed accumulation with a standardized uptake value in the lymph node. Because it was a solitary tumor, we performed tumor resection in October 2009, histopathologically confirming the lymph node metastasis. Subsequently, the patient was again treated with TS-1 monotherapy again until the present. She is currently alive 5 years 9 months after the surgery, without any signs of disease recurrence. PMID- 26805270 TI - [A Case of Gastric Cancer with Adrenal Metastasis That Responded to Chemotherapy]. AB - A 69-year-old man complained of abdominal pain and appetite loss. Advanced gastric cancer with bilateral adrenal metastases( stage IV)was revealed via an examination. XP(cisplatin and capecitabine)chemotherapy was administered. As a result, the tumor was reduced prominently, and his symptoms disappeared 3 months later. However, the cancer recurred 7 months later. Because of the tumor growth, the stent was detained for a passage obstacle by local increase of the tumor 12 months later. The patient died 14 months later. PMID- 26805271 TI - [The Clinical Role of the Neutrophil/Lymphocyte Ratio in Patients with Advanced Gastric Cancer Treated with Protein-Bound Polysaccharide K and Chemotherapy]. AB - This study aimed to evaluate the efficacy of protein-bound polysaccharide K (PSK) containing chemotherapy in patients with unresectable advanced or recurrent gastric cancer (AGC). We retrospectively analyzed 190 patients with AGC who received systemic chemotherapy including 69 patients who were treated with a PSK containing regimen. Using propensity score matching, we obtained 62 matched patients in the S-1 and S-1 plus PSK groups for outcomes analysis. There was a tendency for overall survival to be higher in the S-1 plus PSK group than in the S-1 alone group. In particular, there was a tendency for overall survival in the S-1 plus PSK group to be higher in patients with a neutrophil/lymphocyte ratio (NLR)<2.2 than in patients with a NLR<2.2. There was a tendency for fewer changes in the NLR after the beginning of treatment in the S-1 plus PSK group than in the S-1 alone group. PSK-containing chemotherapy may contribute to improved treatment outcomes of AGC patients. In particular, it may be effective in patients with a high NLR. Further investigations, including a prospective randomized controlled trial, are expected to verify the mechanisms of interaction between cancer cells and the immunoreaction. PMID- 26805272 TI - [Optimal Target Population for Adjuvant Chemotherapy for Pathological T1 Gastric Cancer]. AB - The ACTS-GC trial showed the efficacy of adjuvant treatment with S-1 in patients who had undergone D2 gastrectomy for Stage II or III(excluding pT1) gastric cancer, classified according to the 13th Japanese Classification of Gastric Carcinoma. We retrospectively analyzed the treatment outcomes of pT1 gastric cancer patients who underwent gastrectomy at our institute to determine the optimal target population for adjuvant treatment among these particular patients. Patients with pT1 gastric cancer who underwent gastrectomy for primary gastric cancer at our institute between 2000 and 2008 without perioperative chemotherapy and mortality were included in the current analysis (n=461). The incidence of lymph node metastasis in M and SM patients were 1.7% (4/240) and 16.7% (37/221), respectively. The 5-year relapse-free survival in M and SM patients was 100% and 96.2%, respectively. On multivariate analysis, the most important risk factor for recurrence in SM patients was 3 or more involved nodes (HR: 6.53, [95%CI: 1.10 31.29], p=0.040). The 5-year relapse-free survival in SM patients with involvement of 3 or more nodes was 66.7% and was comparable with that in stage II surgery-only patients in the ACTS-GC trial. Hence, SM patients with 3 or more involved nodes are candidates for effective adjuvant treatment after curative gastrectomy. PMID- 26805273 TI - [A Case of Taxane-Pretreated Metastatic Gastric Cancer with Excellent Response to Nab-Paclitaxel]. AB - We present a rare case of taxane-pretreated metastatic gastric cancer with an excellent response to nab-paclitaxel. A 66- year-old woman was diagnosed with Stage IV gastric adenocarcinoma (T4aN3M1[LYM, OTH]P1CY1). She failed to respond to multiple chemotherapeutic regimens including S-1, capecitabine, cisplatin, L OHP, paclitaxel, docetaxel, and CPT- 11. Finally, 6th line chemotherapy with nab paclitaxel was tried. After 4 courses of nab-paclitaxel, a CT scan revealed decreasing ascites and a reduction in the size of the ovary metastasis. She experienced a clinical response for about 4 months. The adverse events were only Grade 1 peripheral sensory neuropathy and joint pain, and her performance status improved during the treatment period. PMID- 26805274 TI - [Analysis of Chemotherapy with Trastuzumab in Advanced Gastric Cancer]. AB - PURPOSE: Here, we investigated the efficacy of chemotherapy with trastuzumab for patients with advanced or recurrent gastric cancer. MATERIALS AND METHODS: We investigated the progression free survival (PFS) and overall survival (OS) of advanced gastric cancer patients who received first-line chemotherapy with trastuzumab in our hospital. RESULT: After first-line chemotherapy, the median PFS and median OS of patients who received trastuzumab combined with capecitabine/cisplatin chemotherapy was not significantly longer than those of patients who received trastuzumab combined with S-1/cisplatin chemotherapy (PFS, 138 [95%CI: 118-187] vs 169 [95%CI: 83-251] days, p=0.9684; OS, 393 [95%CI: 240 469] vs 466 [95%CI: 256-482] days, p=0.4703). After second-line chemotherapy, the median PFS of patients who received trastuzumab plus irinotecan chemotherapy was not significantly longer than that of patients who received trastuzumab plus paclitaxel chemotherapy (PFS, 63 [95%CI: 52-266] vs 58 [95%CI: 26-184] days, p=0.5447). PMID- 26805275 TI - [A Case of Unresectable Local Recurrence of Gastric Cancer Successfully Resected after Pre-Operative Chemotherapy with Trastuzumab]. AB - A 69-year-old man was diagnosed with advanced gastric cancer and underwent total gastrectomy (tubular adenocarcinoma, tub2, pT3N0M0, stageIIA). Eight months after the surgery, recurrence on the anastomosis was observed. Tumor invasion of the aortic artery was suspected, and the patient was considered inoperable. He was treated with S-1/CDDP plus trastuzumab therapy as a neoadjuvant chemotherapy regimen. After 4 courses of the chemotherapy, significant tumor reduction was observed, and the patient underwent anastomosis resection. Chemotherapy with trastuzumab appears to be an effective NAC treatment for HER2-positive, advanced gastric cancer. PMID- 26805276 TI - [A Patient with Rectal Cancer and Multiple Lung Metastases Treated with XELOX plus Bevacizumab (Bev) Therapy]. AB - The patient was a 76-year-old woman who underwent laparoscopic-assisted low anterior resection for rectal cancer. According to the Japanese classification of colorectal carcinoma (8th Edition), the tumor was tub1, ly0, v0, and pStage I (pT1bN0M0), Cur A. She received no adjuvant chemotherapy. A chest CT scan obtained 42 months after the surgery revealed 3 lung metastases in the left lung, with the biggest measuring 12 mm; the CA19-9 level was elevated to 72U/mL (normal?38 U/mL). She declined surgery for the recurrence. She was treated with XELOX plus bevacizumab (Bev) therapy. Before XELOX plus Bev, the 3 lung metastases had enlarged, with the biggest now measuring 15 mm, and the CA19-9 level was elevated to 166 U/mL. After 4 cycles, the lung metastases decreased in size and the CA19-9 level decreased to 4 U/mL. We did not perform pulmonary resection or additional chemotherapy. No progression of the recurrent tumors was detected on CT after 2 years, and the CA19-9 level was within the normal range. XELOX plus Bev therapy may be effective for unresectable pulmonary metastasis from colorectal cancer. PMID- 26805277 TI - [A Case of Colon Cancer with Multiple Liver Metastases Successfully Treated with Capecitabine/Oxaliplatin plus Bevacizumab]. AB - A 69-year-old woman was diagnosed with descending colon cancer with multiple liver metastases, and a left hemicolectomy was performed. The patient was treated with capecitabine/oxaliplatin (CapeOX) plus bevacizumab (Bmab). After 5 courses of chemotherapy, the number and size of liver metastases remarkably reduced, and after the 12th course, because of peripheral neuropathy, a "stop-and-go"fashion of administering oxaliplatin (L-OHP) was initiated. After 14 courses, the liver metastases had disappeared. After the 33rd course of L-OHP treatment, the patient started receiving capecitabine therapy. The patient is recurrence-free 3 years after surgery, 14 months after achieving a complete response (CR). We report a case of long-term CR after surgery for descending colon cancer with multiple liver metastases, followed by a "stop-and-go" method of administering L-OHP or CapeOX plus Bmab therapy. PMID- 26805278 TI - [A Case in Which Eating Ability Was Restored after Chemotherapy for Gastric Metastasis Following Colon Cancer Resection]. AB - We report here a rare case of gastric metastasis after resection ofa transverse colon cancer in which eating ability was restored following mFOLFOX6 (folinic acid plus fluorouracil plus oxaliplatin) plus cetuximab (Cet) chemotherapy. A 56 year-old man with chief complaints of constipation and abdominal fullness was referred to our hospital. In February 2013, he was diagnosed with transverse colon cancer via enema and colonoscopy. We performed transverse colon cancer resection followed by a 6-month course of capecitabine chemotherapy. In July 2014, the patient's serum carcinoembryonic antigen level increased, in October, he was again referred to our hospital with complaints of appetite loss and vomiting. He was diagnosed with multiple lymph node and gastric metastases via ultrasonography, computed tomography, and endoscopy, as well as multiple lung metastases via computed tomography. As the gastric metastases and vomiting rendered him unable to eat, a nasogastric tube was inserted and was administered mFOLFOX6 plus Cet chemotherapy. After 2 courses of chemotherapy his ability to eat was restored. As of March 2015, the patient remains alive following 12 courses of chemotherapy. PMID- 26805279 TI - [A Case of Disseminated Carcinomatosis of the Bone Marrow with Disseminated Intravascular Coagulation Caused by Cecal Cancer Successfully Treated with mFOLFOX6]. AB - Disseminated carcinomatosis of the bone marrow is often accompanied by disseminated intravascular coagulation syndrome (DIC). This condition is rarely caused by colorectal cancer, and there are no established therapies. OUR CASE: A 66-year-old woman was admitted to our hospital because of DIC. She had been diagnosed with cecal cancer and multiple metastases of the lymph nodes, liver, and bone. She was diagnosed with disseminated carcinomatosis of the bone marrow and treated with systemic chemotherapy by modified FOLFOX6 (mFOLFOX6). Subsequently, the DIC rapidly resolved, and she was discharged from the hospital. PMID- 26805280 TI - [A Case of Rectal Cancer Successfully Treated with Stereotactic Radiotherapy for Liver and Lung Metastases]. AB - An 84-year-old patient underwent anterior resection for rectal cancer (RS, T4a, N2, M0, Stage IIIb), without adjuvant chemotherapy. Liver metastasis 30 mm in diameter was found in the S7/8 segment 2 years and 6 months after surgery, and segmentectomy of the liver was performed. One year after hepatectomy, lung metastasis 9 mm in diameter was detected in the right S1 lobe. The tumor enlarged after a 2-month follow-up period. We decided to apply stereotactic radiotherapy (50 Gy/10 Fr) to control the lesion. The tumor shrunk and became a scar after treatment. The patient was in good health without any recurrences 7 months after stereotactic radiotherapy. Surgical resection is an optimal method to control lung metastasis from colon cancer when operable; however, there are cases with no indication for surgery due to co-morbidities. Stereotactic radiotherapy can be an effective treatment for lung metastasis from colon cancer when surgery is contraindicated. PMID- 26805281 TI - [Tolerability of Oxaliplatin-Based Adjuvant Chemotherapy for Patients with Colorectal Cancer]. AB - OBJECTIVE: Although the efficacy of adjuvant chemotherapy with oxaliplatin for colorectal cancer patients has been established, the tolerability of this regimen is rarely reported in Japan. The aim of this study was to clarify the tolerability of adjuvant oxaliplatin-based regimen for Japanese patients with colorectal cancer. METHODS: This study included 158 advanced colorectal cancer patients who consecutively underwent a surgical procedure at our hospital and received adjuvant chemotherapy. Completion rate and adverse events were monitored in this study. RESULTS: Among the 158 patients, 44 received oxaliplatin-based chemotherapy and the remaining received chemotherapy without oxaliplatin. The use of oxaliplatin was significantly correlated with more cases of adverse events such as myelosuppression (p<0.001) and peripheral neurotoxicity (p=0.005), which lead to dose reduction (p<0.001) or drug withdrawal (p<0.001). However, the completion rate did not significantly differ between the 2 groups. The median relative dose intensity (RDI) was 85.7%, which means that the oxaliplatin-based regimen is feasible. As for recurrence-free survival, no significant differences were observed between the 2 groups. CONCLUSION: This study demonstrates that adjuvant chemotherapy with oxaliplatin is tolerable by colorectal cancer patients in Japan. PMID- 26805282 TI - [A Case of Ascending Colon Cancer with Extra Iliac Lymph Node Metastases]. AB - We report a case of ascending colon cancer with right extra iliac lymph node metastases. A 60s-year-old woman underwent right hemicolectomy with lymph node dissection in July 2011. Pathological diagnosis was T4 (SE), N1 (2/42), M0, stage IIIA. Adjuvant chemotherapy with tegafur/uracil was administered after the operation for 6 months. One year after the operation, the serum carcinoembryonic antigen (CEA) level was gradually increasing. Three years after the operation, positron emission tomography-computed tomography (PET-CT) delineated a 3 cm mass with an abnormal signal on the right lower abdominal side of the external iliac vessels. The diagnosis was an isolated remnant tumor in the right extra iliac vessels area from the primary ascending colon cancer. Other recurrent lesions were not found; therefore, resection of this mass was performed. Pathological findings confirmed lymph node metastases from the ascending colon cancer. This type of metastasis is extremely rare, and more case reports are needed to determine the mechanism behind these metastases. PMID- 26805283 TI - [Long-Term Survival of a Patient with Colon Cancer with Peritoneal Dissemination]. AB - This case involves a 76 year-old woman. A sigmoidectomy was performed for sigmoid colon cancer in August 2006. On histological examination, the cancer was shown to be tub2>tub1>por2, pSE, int, INF b, ly2, v0, pN0, p1 (Douglas), Stage IV. After surgery, 4 courses of FOLFOX and 8 courses of TS-1 plus CPT-11 were administered after UFT plus LV was performed. Because of suspected recurrence at the anastomotic site, a partial colectomy was performed in September 2010, and TS-1 was started after surgery. In March 2012, the carcinoembryonic antigen level had increased to 13.7 ng/mL. Irregular masses with spicula, 13*15 mm and 19*23 mm on the right and left sides, respectively, were observed on chest computed tomography, and lung metastasis was suspected. Left lower and partial right middle lobectomies were performed. After surgery, the tumor marker levels were normalized. Chemotherapy was not performed. Currently, at 2 years 8 months after resection of the lung metastases, no recurrence was observed. Long-term survival in cases of colon cancer with peritoneal dissemination is rare, but multidisciplinary treatment, including surgical treatment, showed the promising possibility of long-term survival. PMID- 26805284 TI - [A Case of Pseudomyxoma Peritonei Derived from Cecum Colon Cancer with Long-Term Recurrence-Free Survival]. AB - A 29-year-old woman was diagnosed with advanced cecum colon cancer, and right hemicolectomy was performed. The pathological findings showed stage IIIa disease, including moderately differentiated tubular adenocarcinoma>mucinous adenocarcinoma, pT3, pN1, cM0, and Cur A resection. The patient was treated with 5-FU plus l-LV adjuvant chemotherapy. Fourteen months after surgery, bilateral ovarian metastasis and ascites were found, and another surgery was performed, revealing that the abdominal cavity was filled with a gelatinous ascites. Under the diagnosis of pseudomyxoma peritonei, resection of both ovaries, abdominal lavage, and intraperitoneal administration of CDDP were performed, followed by S 1 plus CDDP treatment. Two years after the recurrence, peritoneal re-recurrence on the vaginal fornix was detected. A total hysterectomy, partial vaginectomy, and resection of disseminated peritoneal nodules were performed. The patient received mFOLFOX6 treatment postoperatively. To date, 8 years and 9 months after her re-recurrence, the patient is alive and without signs of a third recurrence. PMID- 26805285 TI - [A Case of Cecal Cancer with Multiple Cutaneous Metastases]. AB - We encountered a case of cutaneous metastases from colorectal carcinoma. A 63 year-old woman underwent laparoscopic-assisted ileocecal resection for cecal cancer. Computed tomography (CT) showed multiple liver metastases. The tumor was diagnosed as a well-differentiated adenocarcinoma and was staged as pSE, pN1, sH2, ly1, v1, CP0cM0, fStage IV. She was treated with 33 courses of the 5 fluorouracil, Leucovorin, and irinotecan (FOLFIRI) regimen and 15 courses of the 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab regimen. Thirty-four months after resection, multiple cutaneous tumors were noted, predominantly on the lower abdomen, and we resected 2 of them. Histologically, the specimens were diagnosed as well-differentiated adenocarcinoma, which was similar to that of cecal carcinoma. After 1 course of regorafenib, she died 3 years after the primary surgical resection. PMID- 26805287 TI - [Two Cases of Digestive Organ Cancer in Patients with Situs Inversus Treated with Laparoscopic Surgery]. AB - Case 1: A 53-year-old woman had a positive fecal occult blood test during an examination performed in June 2014, and she visited our department in August. Colonoscopic examination showed a type 2 rectal cancer 4 cm from the anal verge. CT showed situs inversus totalis. We performed laparoscopic abdominoperineal resection (D2) for a diagnosis of cT1b, N0, M0, Stage Irectal cancer. Case 2: A 60-year-old man had a positive fecal occult blood test. Colonoscopic examination showed a type 2 cancer of the ascending colon. Chest radiography showed dextrocardia, but the arrangement of the organs in the abdomen was normal. We performed laparoscopic ileocecal resection (D3) for a diagnosis of cT2, N0, M0, StageI colon cancer. Laparoscopic surgery can be performed safely in patients with situs inversus totalis. PMID- 26805286 TI - [A Case of Bullous Pemphigoid Relieved after Sigmoid Colon Cancer Resection]. AB - A 76-year-old man presented with many bullous lesions and erythema over his whole body in August 2014. Blood examination showed an elevation of the anti-BP180 antibody (658 U/mL) and a biopsied specimen of the skin lesions showed subepidermal bulla. A diagnosis of bullous pemphigoid was made based on the clinical and histological findings. Although 20 mg/day of prednisolone was administered, there was a poor response and consequently the dose of steroid was increased to 70 mg/day after 2 weeks. Bullous pemphigoid related to a malignant tumor was suspected. Colonic endoscopic examination revealed a sigmoid colon cancer and he underwent a sigmoidectomy with lymphodenectomy. The histopathological findings revealed a moderately-differentiated adenocarcinoma, pT1b, pN1, pStage IIIa, and he received adjuvant chemotherapy(UFT/ LV). The dermatological findings were rapidly relieved after tumor resection and anti BP180 antibody was normalized. He has had no signs or symptoms of recurrence, both of the cancer and the bullous pemphigoid, for 9 months after the operation. PMID- 26805288 TI - [Laparoscopic Surgery for T4b Colorectal Cancer]. AB - BACKGROUND: It is considered difficult to perform laparoscopic surgery for colorectal cancer with T4b that is directly invades to adjacent organs. This retrospective study evaluated pT4b colorectal cancer in terms of the efficacy of laparoscopic surgery. METHODS AND RESULTS: Forty-six cases with pT4b colorectal cancer that occurred between 2006 and 2014 were investigated. Laparoscopic surgery (LAC) was performed in 20 cases, of which 5 were conversions, and open surgery (OC) was performed in 26 cases. Pathologically-proven invaded organs resected by LAC were the abdominal wall (n=6), greater omentum (n=5), small intestine or colon (n=3), bladder, appendix, or ovary (n=1). Organs resected by OC were the abdominal wall (n=8), bladder (n=5), colon, greater omentum, or small intestine (n=3), stomach, ovary, spermatic duct (concurrent with bladder), prostate, or sacrum (n=1). Operation time (median) was 275 min for LAC and 260 min for OC. Blood loss (median) was 100 mL for LAC and 410 mL for OC. The duration of hospital stay (median) was 15 days after LAC and 18 days after OC. There were 2 cases with morbidities greater than Grade 3 after LAC and 1 case after OC. There was 1 hospital death in the OC group. CONCLUSION: Laparoscopic surgery for T4b colorectal cancer can be feasible in select cases. PMID- 26805289 TI - [Surgical Simulation-CT Colonography for Laparoscopic Assisted Sigmoid Colectomy Preserving the Inferior Mesenteric Artery and Vein]. AB - D2 lymph node dissection in laparoscopic surgery for early colon cancer requires selective vessel dissection, making it technically very difficult. Using surgical simulation-CT colonography (simulation-CTC), we could perform laparoscopic assisted sigmoid colectomy preserving the inferior mesenteric artery (IMA) and vein (IMV) more accurately and safely. The case described here was a type 0-Ip sigmoid colon cancer with a tumor size of 13 mm. Endoscopic mucosal resection was performed to confirm a pathological diagnosis of pT1b (4,000 mm) and v1. Sigmoid colectomy was planned, and simulation-CTC was performed, which demonstrated that the cancer was located in the proximal sigmoid colon and supplied by the first sigmoid colon artery (S1). To maintain the blood flow to the distal sigmoid colon, selective S1 resection preserving the IMA and IMV was planned. At the operation, S1, which branches off from the IMA near the bifurcation of the abdominal aorta, was dissected, and the vein accompanying S1, which branches from the IMV in the same area as S1, was dissected. The operation was performed accurately according to the plan, showing that simulation-CTC can be very useful. PMID- 26805290 TI - [A Case of RFA for Liver Metastasis after Resection for Rectal Cancer in a 102 Year-Old Man]. AB - A 100-year-old man was admitted to our hospital because of bloody stool. Colonoscopy revealed a type-2 tumor in the rectum, which was diagnosed as moderately differentiated adenocarcinoma. There was no distant metastasis on CT. After meticulous preoperative evaluation of surgical risks considering his age, laparoscopic high anterior resection was performed. During surgery, the edge of the descending colon showed ischemia; therefore, we performed conversion to open surgery and transverse colon resection. However, the edge of the transverse colon showed ischemia; therefore, ascending colon resection and ascending colon-rectum anastomosis were performed. On day 5 after surgery, the patient developed aspiration pneumonia, for which respirator management was conducted. As his condition improved, he was discharged on postoperative day 32. The pathology results were tub2, pT3, ly0, v2, PM0, DM0, RM0, pN1, Stage IIIa. One year 6 months after the surgery, when the patient was 102 years old, CT revealed liver metastasis. RFA was performed for the liver lesion. In people aged 100 years or older, few reports are available on colectomy, and there is no report of treatment for metastasis. PMID- 26805291 TI - [The Outcomes of Laparoscopy-Assisted Surgery in Elderly Patients with Colorectal Carcinoma]. AB - AIM: To evaluate short-term outcomes of laparoscopy-assisted colectomy (LAC) in elderly patients with colorectal carcinoma. METHODS: A total of 289 colorectal cancer patients underwent LAC between 2008 and 2013. They were divided into an elderly group (<80 years of age, group E), and a younger group (<80 years of age, group Y). The treatment results, including the surgery-related factors, the perioperative course, and the pre- and postoperative complications, were retrospectively analyzed. RESULTS: There were 49 patients in group E, and 240 patients in group Y. There was no significant difference between the 2 groups considering the operative time, blood loss, rate of transfusion, post-operative hospital stay, rate of conversion to open surgery, or rate of complications, except for the number of patients with an ASA classification of greater than Grade 2 and the degree of lymph node dissection. CONCLUSIONS: LAC in elderly patients was found to be relatively safe because it was associated with a reduction in damage to the abdominal wall, and with an early recovery from surgery. These results suggest that the indications of LAC could be expanded for elderly patients. PMID- 26805292 TI - [A Case of Idiopathic Thrombocytopenic Purpura during Adjuvant Chemotherapy for Colon Cancer]. AB - A 76-year-old man underwent surgery for sigmoid colon cancer. The pathological finding was stage II with a high-risk of recurrence (SI [bladder], l y0, v2, pN0, H0, P0, M0). He was treated with TS-1 as adjuvant chemotherapy. After the 1 course of chemotherapy, his platelet count was 4,000/mL. The high index of platelet associated IgG (PA-IgG) and bone marrow examination suggested that thrombocytopenia was caused by idiopathic thrombocytopenic purpura. The platelet count improved by prednisolone administration and Helicobacter pylori eradication treatment. After 6 months with no administration of adjuvant chemotherapy, the colon cancer recurred locally, and we performed a Hartmann's operation. PMID- 26805293 TI - [A Case of Gastrointestinal Perforation in a Patient with Colon Cancer and Stent Placement during Bevacizumab Treatment, Alleviated with Conservative Therapy]. AB - The case involved a 52-year-old man. He was diagnosed with sigmoid colon cancer and multiple liver and lung metastases. After placement of a metallic stent for circumferential stricture, 5-fluorouracil/Leucovorin/oxaliplatin (FOLFOX4) plus bevacizumab therapy was introduced. After 17 courses, gastrointestinal perforation was noted at the site of stent placement, but this was alleviated with conservative therapy. Although gastrointestinal perforation is known to be a serious complication that occurs during chemotherapy combined with bevacizumab, further studies are needed to investigate the incidence of gastrointestinal perforation after stent placement more fully. PMID- 26805294 TI - [A Case of Abdominal Wall Hernia Rupture during Bevacizumab Treatment]. AB - A 78 -year-old man with rectal cancer underwent abdominoperineal resection of the rectum. In the postoperative period, the patient experienced wound infection, leading to an abdominal wall hernia. Two years following surgery, a rise in the serum CEA level was seen. A metastatic tumor was detected in the right lung on chest CT. VATS right lung inferior lobe segmental resection was performed. After lobectomy, the serum CEA level continued to increase. Another metastatic tumor was detected in the right lung on chest CT. Chemotherapy with capecitabine, oxaliplatin, and bevacizumab was commenced. The erosive part of the abdominal wall scar hernia extended during the nine weeks of chemotherapy. The chemotherapy was then discontinued. In the follow-up CT scan, a right pleural recurrence, local recurrence in the pelvis, and a liver metastasis were detected. Chemotherapy was re-introduced 3 years after surgery. The erosive part of the abdominal wall hernia again began to spread with chemotherapy recommencement. Four months after restarting chemotherapy, the hernia ruptured, with a loop of the small intestine protruding out of it. The patient covered this with a sheet of vinyl and was taken by the ambulance to our hospital. The erosive part of the abdominal wall hernia had split by 10 cm, and a loop of the small intestine was protruding. As ischemia of the small intestine was not observed, we replaced it into the abdominal cavity, and performed a temporary suture repair of the hernia sac. Following this, bevacizumab was discontinued, and the erosive part reduced. We performed a radical operation for abdominal wall scar hernia repair 11 weeks after the discontinuation of bevacizumab. PMID- 26805295 TI - [A Case of Colorectal Cancer with Anaphylactic Shock to Oxaliplatin]. AB - We present the case of a 61-year-old woman with cecum cancer, ileal and multiple hepatic metastases, and peritoneal dissemination. Surgery (right hemicolectomy) was performed on December 2013. After surgery, 7 courses of mFOLFOX6 plus bevacizumab were administered. In May 2014, 4 minutes after starting the 8th course of oxaliplatin, dyspnea, nausea, vomiting, and general malaise were observed. Oxaliplatin administration was immediately discontinued and an injection of an antiemetic drug was administered, but the patient's blood pressure dropped to 87/53 mmHg and the SpO2 decreased to 87% (room air). The patient showed facial pallor; oxygen administration was initiated. Although blood pressure recovered to 124/69 mmHg 3 minutes after oxygen administration, reddening of the palms, pruritus, and headache were observed. The dyspnea eased 8 minutes after oxygen administration, the SpO2 recovered 18 minutes after oxygen administration, and the headache ceased. The patient subsequently was admitted to the hospital for observation, but no significant change was observed, and she was discharged the following day. Anaphylaxis due to oxaliplatin occurring after the 6th course is commonly reported, and the symptoms in this case were comparable to those described in the literature. PMID- 26805296 TI - [A Case of Drug-Induced Thrombocytopenia Resulting from Sensitivity to Oxaliplatin]. AB - A 67-year-old man was diagnosed with pulmonary metastasis from advanced transverse colon cancer. Thus, a local resection was performed. Adjuvant chemotherapy with mFOLFOX6 was started. Sixteen courses were carried out without problems. However, he complained of chills and chest discomfort 2 hours after beginning the 17th course of chemotherapy. Laboratory data showed remarkable thrombocytopenia, and platelet-associated IgG level was high. After administration of steroids and platelet transfusions, the platelet count improved. Therefore, we diagnosed drug-induced thrombocytopenia resulting from sensitivity to oxaliplatin (L-OHP). Since then, sLV5FU2 therapy was started, and the patient received the whole adjuvant chemotherapy without problems. Thrombocytopenia resulting from sensitivity to L-OHP is a relatively rare side effect. We herein report this case with a review of the relevant literature. PMID- 26805297 TI - [A Case of Consciousness Disturbance Caused by Hyperammonemia during a mFOLFOX6 Regimen for Metastatic Colon Cancer]. AB - Systemic chemotherapy based on 5-fluorouracil (5-FU) is a standard treatment for unresectable or recurrent colorectal cancer. Although hyperammonemia is known as one of the adverse side effects of 5-FU, a disturbance of consciousness caused by hyperammonemia is not a usual finding. We encountered a case of 5-FU-related consciousness disturbance with respiratory depression. A woman in her sixties was diagnosed with metastatic cecum cancer, involving peritoneal dissemination and hydronephrosis due to retroperitoneal invasion. After resection of the primary lesion, systemic chemotherapy, including capecitabine, irinotecan, bevacizumab and cetuximab, was administered for the metastatic lesions. As a third-line of treatment, the mFOLFOX6 plus bevacizumab regimen was administered. On the second day of the first course, the patient complained of nausea and vomiting. On third day, her consciousness level was deteriorating. The level of ammonia in the blood was abnormally high. Therefore, we diagnosed consciousness disturbance caused by hyperammonemia resulting from high-dose 5-FU infusion. The symptom improved immediately after mechanical ventilation and intravenous infusion. Renal dysfunction is considered a risk factor for hyperammonemia caused by 5-FU, and it is necessary to pay particular attention in patients with renal dysfunction who receive chemotherapy with 5-FU. PMID- 26805298 TI - [A Case of Sigmoid Colon Cancer with Synchronous Liver Metastasis, Treated with Laparoscopic Liver Resection after SOX plus BV Chemotherapy]. AB - We performed laparoscopic liver resection in a patient with synchronous liver metastasis from advanced sigmoid colon cancer after induction with S-1 plus oxaliplatin (SOX) plus bevacizumab (BV) chemotherapy. A 61-year-old woman underwent laparoscopy-assisted sigmoidectomy for locally advanced sigmoid colon cancer with synchronous liver metastasis. SOX plus BV chemotherapy was initiated. After 3 courses, the liver tumor was downsized, and metastasectomy was performed laparoscopically with R0 resection. The postoperative course was uneventful and the patient was discharged on the 11th postoperative day. She has been free from recurrence. Induction with SOX plus BV chemotherapy is considered to be not only effective, but also beneficial for maintaining the quality of life (QOL) in patients with advanced colorectal cancer. PMID- 26805299 TI - [A Case of Simultaneous Laparoscopic Resection of Sigmoid Colon Cancer and Liver Metastases after Chemotherapy with Modified FOLFOX6 plus Panitumumab]. AB - A 70s-year-old man was referred to our hospital because of sigmoid colon cancer. Computed tomography (CT) revealed a large mass in the right lobe of the liver and small masses in Couinaud segments IV and VI. We started systemic chemotherapy with mFOLFOX6 and panitumumab. After 6 courses of the treatment, the size and number of the liver metastases was remarkably reduced on CT. We performed a simultaneous laparoscopic resection for the primary tumor and synchronous liver metastases. The postoperative course was uneventful and he had no signs of recurrence 12 months after surgery. PMID- 26805300 TI - [A Case of Pathological Complete Response after Primary Tumor Resection Followed by Hepatectomy-A Sigmoid Colon Cancer with Synchronous Liver Metastases]. AB - The case is of a 62-year-old man with no medical history and no family history.A type 2 tumor was found in the entire circumference of the sigmoid colon by colonoscopy after a positive result on a fecal occult blood test, and 5 liver metastases were recognized in both lobes of the liver by using contrast-enhanced CT.He was first treated by primary tumor resection. Subsequently, 5 fluorouracil/l-leucovorin/oxaliplatin (mFOLFOX6) plus bevacizumab (BV) was started 1 month after the surgery and a total of 8 cycles of mFOLFOX6 plus BV were administered without any adverse events.On CT assessment after the chemotherapy, the patient was diagnosed with stable disease according to RECIST guidelines since the size of the tumor only showed a slight reduction.However, it was considered to be an optimal response based on the morphologic criteria. Thereafter, a medial segmentectomy and partial resection of the liver was performed.A mucus reservoir was found in the tumor site, and no viable tumor cells were detected pathologically, which confirmed the pathological complete response with mFOLFOX6 plus BV. PMID- 26805301 TI - [Simultaneous Resection of Sigmoid Colon Cancer and Synchronous Liver Metastasis by Laparoscopic Surgery]. AB - We report the case of a patient with sigmoid colon cancer with synchronous liver metastasis who underwent simultaneous sigmoid colectomy and partial hepatectomy by laparoscopic surgery. A 70-year-old man with positive fecal occult blood was diagnosed with sigmoid colon cancer and referred to our hospital. Staging computed tomography (CT) revealed a solitary liver metastasis in segment 6, confirmed by magnetic resonance imaging (MRI). He underwent simultaneous laparoscopic sigmoid colectomy and partial hepatectomy. The patient's postoperative recovery was uneventful and he was discharged 12 days later. The patient was alive without recurrence 4 months after surgery. Laparoscopic surgery is an accepted mode of treatment for colorectal cancer. However, the use of laparoscopy in liver surgery is still limited. There have only been few case reports of combined laparoscopic colorectal and liver resection. Simultaneous laparoscopic colectomy and hepatectomy is feasible for selected colorectal cancer patients with liver metastases. It may provide significant decrease in morbidity, length of hospitalization time, and intraoperative blood loss, without compromising curability or increasing mortality. Further studies are needed to confirm the feasibility of this approach. PMID- 26805302 TI - [Two Cases of Curative Resection of Locally Advanced Rectal Cancer after Preoperative Chemotherapy]. AB - Reports of conversion in cases of locally advanced colorectal cancer have been increasing. Here, we present 2 cases in which curative resection of locally advanced rectal cancer accompanied by intestinal obstruction was achieved after establishing a stoma and administering chemotherapy. The first case was of a 46 year-old male patient diagnosed with upper rectal cancer and intestinal obstruction. Because of a high level of retroperitoneal invasion, after establishing a sigmoid colostomy, 13 courses of mFOLFOX6 plus Pmab were administered. Around 6 months after the initial surgery, low anterior resection for rectal cancer and surgery to close the stoma were performed. Fourteen days after curative resection, the patient was discharged from the hospital. The second case was of a 66-year-old male patient with a circumferential tumor extending from Rs to R, accompanied by right ureter infiltration and sub intestinal obstruction. After establishing a sigmoid colostomy, 11 courses of mFOLFOX6 plus Pmab were administered. Five months after the initial surgery, anterior resection of the rectum and surgery to close the stoma were performed. Twenty days after curative resection, the patient was released from the hospital. No recurrences have been detected in either case. PMID- 26805303 TI - [A Case of Recurrent Sigmoid Cancer after EMR Curatively Resected after Neoadjuvant Chemotherapy]. AB - The Guidelines for Colorectal Cancer Treatment list indication and curative resection criteria for the endoscopic resection of mucosal and submucosal invasive colorectal cancers. Here, we report the case of a woman who underwent endoscopic mucosal resection (EMR) but should have undergone curative resection because the submucosal invasion depth in this case was 1,200 mm; however, she did not undergo additional curative surgery. Although liver and lymph node metastases were observed 7 years later, we were able to resect all of these tumors after neoadjuvant chemotherapy. We strongly recommend additional curative surgery for patients who fulfill the criteria for curative resection after EMR because of the very high recurrence rates in such cases. PMID- 26805304 TI - [A Successful Curative Resection Including Replacement with a Ringed Gore-Tex Tube Graft for Local Recurrence after Right Adrenalectomy and Liver Metastasis of Colon Cancer with Inferior Vena Cava Invasion]. AB - A 65-year-old woman underwent sigmoidectomy for colon cancer in January 2002. She had multiple liver metastases and received systemic chemotherapy (UFT-E plus CPT 11) for 6 months. She underwent partial hepatectomy of S7 and S3 and cholecystectomy in July 2003. After 4 years without recurrence, right adrenal and para-aortic lymph nodes metastases were detected and she underwent right adrenalectomy and para-aortic lymphadenectomy in July 2007. In July 2008, local recurrence (1 cm in size) was identified in the cavity of the right adrenal gland. She received chemotherapy (mFOLFOX6 plus bevacizumab) for 5 years. In May 2013, PET-CT showed abnormal accumulation of FDG in S7 of the liver (SUVmax 6.7). The enhanced EOB-MRI showed a mass lesion in S7 (3 cm in size) and 2 nodules (1 cm in size) in S3 and S4. We scheduled for liver surgery with reconstruction of the inferior vena cava (IVC) after systemic chemotherapy (FOLFIRI plus cetuximab). The patient underwent partial hepatectomy of the tumor in S7 combined with resection of the diaphragm and IVC. Reconstruction of the IVC was performed using a ringed Gore-Tex tube graft in February 2014. The patient is still alive without recurrence 18 months after surgery. PMID- 26805305 TI - [A Case of Long-Term Survival of a Patient with Liver Metastasis of Colon Cancer and Suspected Inferior Vena Cava Invasion]. AB - A 58-year-old woman was diagnosed with a sigmoid colon cancer and synchronous liver metastasis. Because an obstruction of the sigmoid colon was identified, the patient underwent sigmoidectomy. Computed tomography(CT)findings suggested possible vena cava and hepatic vein invasion. Therefore, the decision was made to offer systemic chemotherapy. The patient underwent 6 courses of chemotherapy with 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6). After 4 courses of chemotherapy, CT scans showed a significant reduction of the liver metastasis (reduction rate of 5 0%; a partial response) and demonstrated improved exclusion of the inferior vena cava and hepatic vein. After 6 courses of chemotherapy, we performed right trisegmentectomy of the liver and resection of the inferior vena cava and diaphragm. Postoperative pathological findings revealed negative margins, and no invasion of the inferior vena cava. The pathological response grade of the tumor after chemotherapy was determined to be Grade 2. Adjuvant chemotherapy was not performed because of the patient 's poor performance status. The patient was alive with no recurrence 8 years after resection of the liver metastasis. PMID- 26805306 TI - [A Case of Repeat Liver Resection after Laparoscopic Resection of a Synchronous Liver Metastasis of Colon Cancer]. AB - A 44-year-old woman with subileus was diagnosed with advanced sigmoid colon cancer with a synchronous liver metasta- sis (segmanet 5/8). Laparoscopic anterior resection was performed, and histological diagnosis was sigmoid colon cancer, 55*40 mm, type 2, tub2>por2, pT3, ly2, v2, pN1, M1a, Stage IV (Japanese Classification of Colorectal Carcinoma, Eighth edition). Four courses of neoadjuvant chemotherapy (FOLFIRI plus panitumumab) shrank the liver metastasis. Laparoscopic partial liver resection was performed for 285 minutes, with 350 g of blood loss. The patient was discharged 9 days after the operation. Two courses of oral adjuvant chemotherapy (S-1) was performed but discontinued owing to side effects. Seven months after the surgery, computed tomography revealed 2 small liver metastasis (segment 8). Although the sizes were 35 and 5 mm, respectively, the larger mass was closed to the middle and right hepatic vein. Therefore, open hepatectomy was performed for 285 minutes, with 525 g of blood loss. The patient was discharged 9 days after the operation without complication. The patient had no recurrence for 1 year after the last surgery. PMID- 26805307 TI - [A Case of Long-Term Survival after Nine Surgeries for Recurrent Sigmoid Colon Cancer]. AB - A 67-year-old man was operated for sigmoid colon cancer. Histopathological examination revealed pT3 (SS), N0, M0, Stage II cancer. In March 2005, abdominal computed tomography (CT) showed recurrences in the abdominal wall and associated localized dissemination. The patient underwent chemotherapy using TS-1 and CPT 11; however, the disease progressed. Therefore, surgery was performed to resect the recurrences. A re-recurrence developed during the adjuvant chemotherapy. The patient was operated 9 times for recurrences, which were macroscopically resectable, in addition to chemotherapy and radiation. It has been 3 years and 7 months since the last operation, and he is alive with no recurrence. Metachronous peritoneal seeding and distant metastasis developed, but we have observed that surgical resection of each recurrence can prolong patient survival. We conclude that surgical resection can become a treatment of choice for resectable metachronous peritoneal seeding from colon cancer. PMID- 26805308 TI - [Colorectal Cancer with Macroscopic Invasion to Adjacent Organs--A Case Report]. AB - We encountered a case of colorectal cancer with macroscopic invasion to the adjacent organs. A 61-year-old man with abdominal pain and nausea was diagnosed as having sigmoid colon cancer invading the ileum, ureter, internal iliac artery, and external iliac vein. A lower anterior resection and resection of the small bowel, ureter, external iliac vein, and internal iliac artery was performed and succeeded in an R0 resection. The patient was discharged from the hospital in 29 POD. Pathology results revealed an adenocarcinoma, pT4b, pSI, INF b, int, ly0, v, pPM0, pDM0, pN0, Type 2, Stage II. Four courses of XELOX plus bevacizumab were administered. The patient underwent ileostomy closure, and is currently free of relapse 3 years 2 months after resection. The survival rate of patients with combined resection of the invaded organs is significantly higher than that of patients with a non-combined resection. The survival rate after curative resection is also significantly higher compared with non-curative resection. Aggressive resection of invaded organs seems to be important for a good outcome. PMID- 26805309 TI - [Resection of the Right External Iliac Artery and Vein after Local Recurrence of Cecal Cancer]. AB - A 62-year-old woman was admitted with abdominal pain and distention in July 2013. Computed tomography (CT) revealed a small bowel obstruction caused by an ileocecal tumor, and colonoscopy revealed a type 3 cecal tumor. Because an ileus tube was not effective to relieve her symptoms, she was transferred to the Department of Surgery for an emergency operation. Open resection of the ileocecal tumor along with the right ureter and psoas was performed. Histological examination showed that cancer cells were present in the radial margin. The patient was treated with a post-operative course of chemotherapy (capecitabine and oxaliplatin), but the level of carcinoembryonic antigen was increasing; positron emission tomography (PET) revealed a local cancer recurrence. Although the right external iliac artery and reconstructed right ureter were encased by the tumor, there were no signs of lymph node metastasis or distant metastasis. Because the tumor was localized, we decided to perform a re-excision. Intraoperatively, the right external iliac vein was difficult to separate from the tumor. Therefore, we resected the right ureter, kidney, and right external iliac artery and vein en bloc. The right external iliac artery and vein were replaced with grafts. Histopathologically, the reconstructed right ureter was completely invaded by the tumor, and cancer cells had invaded the nearby adventitia of the artery, but the surgical margin was negative. Four months after the second operation, peritoneal dissemination was detected on PET. The patient was followed-up in an outpatient clinic without chemotherapy. PMID- 26805310 TI - [A Case of FAP Who Underwent Mucosectomy for Intramucosal Cancer That Repeatedly Developed in the Residual Rectal Mucosa after Stapled Ileal-Pouch Anal Anastomosis]. AB - When we perform stapled ileal pouch anal anastomosis (IPAA) for familial adenomatous polyposis (FAP), some rectal mucosa persists. There is no consensus on surgical treatment when cancer develops at the residual mucosa. We report the case of a 43-year-old woman who repeatedly underwent endoscopic resection for intramucosal cancer that developed in the residual rectal mucosa 6 years after stapled IPAA, which she received at age 33. She was referred to our department for surgical treatment. We performed mucosectomy for the residual rectum mucosa, including a 0-IIa lesion at the anterior wall. Two months later, stenosis was observed at the anastomotic site. We repeatedly conducted balloon expansion of the stenotic lesion. Six months later, the resected lesion was covered with white epithelium, and columnar epithelium was confirmed by step biopsy of the epithelium from the dentate line to the ileoanal pouch anastomotic site. This finding indicated that the regenerating epithelium was derived from the epithelium from the anal side. The patient remains well after 2 year 4 months with no complaints. PMID- 26805311 TI - [A Case of Synchronous Double Colitic Cancer in Crohn's Disease]. AB - A 43-year-old man with a 23-year history of remission for Crohn's disease was admitted to our hospital because of stomachache and anal pain. Computed tomography showed fistula formation between the ileum and the sigmoid colon. Colonoscopy revealed two elevated tumors in the rectosigmoid and lower rectum. Synchronous double colitic cancer with Crohn's disease was diagnosed. We performed an abdominoperineal resection and an ileocecal resection. Histopathological examination revealed a rectosigmoid tumor invading the ileum and bladder with intestinal mesenteric and lateral lymph node metastasis, Stage IV. Postoperatively, the patient received adjuvant chemotherapy with mFOLFOX6 plus bevacizumab. Nine months after the operation, he was diagnosed with right pleural dissemination and effusion. He died after 13 months. Synchronous double colitic cancer in Crohn's disease is very rare and is often advanced at the time of diagnosis. These findings suggest that patients with Crohn's disease need periodic surveillance. PMID- 26805312 TI - [A Patient with Recurrent Ulcerative Colitis-Associated Rectal Cancer Attaining a Complete Response with FOLFIRI plus Bevacizumab]. AB - A 60-year-old man underwent laparoscopic total proctocolectomy with ileostomy for advanced ulcerative colitis-associated rectal cancer. The final diagnosis was advanced cancer pT3, pN2 and M0 (pStage IIIb). Adjuvant therapy with XELOX was performed. However, abdominal CT revealed a liver metastasis and lymph node metastases in the pelvis 6 months after surgery. The patient was treated with FOLFIRI plus bevacizumab. After 20 courses of chemotherapy, the patient was considered to have experienced a clinical CR, which has been maintained for 3 years 5 months. PMID- 26805313 TI - [A Case of Colon Cancer with Familial Adenomatous Polyposis Showing MSI-H and Deletion of MSH2/MSH6 Protein]. AB - A 31-year-old woman with familial adenomatous polyposis (FAP) was diagnosed with colon cancer. Genetic testing showed a germ cell line mutation of APC (a frame shift mutation). Moreover, deletion of MSH2/MSH6 protein and high microsatellite instability (MSI-H) was detected. Therefore, Lynch syndrome (LS) associated with FAP was suspected. Additional analysis showed no pathogenic mutation of MSH2 and no change in the number of copies or methylation in the promoter region. Therefore, this was not a case of LS caused by a genetic germ cell line mutation. The chromosome instability had been caused by a malfunction of APC, and it produced a structural change in a gene in the somatic cells. This case is very interesting. PMID- 26805314 TI - [A Family Affected by Lynch Syndrome Caused by MSH6 Germline Mutation]. AB - The clinical features of Lynch syndrome caused by MSH6 are not fully understood since very few cases have been described in Japan. We report 2 cases of Lynch syndrome with germline mutation of MSH6 in a family. Case 1: A 47-year-old man was referred to our department due to positive fecal occult blood test. He had family history of endometrial cancer and gastric cancer (mother), and bladder cancer (father). We performed sigmoidectomy for sigmoid cancer. The pathological findings revealed mucosal cancer (pTis, pN0, H0, P0, pStage 0). Since the patient met the revised Bethesda guidelines, we performed microsatellite instability (MSI) testing and immunohistochemistry for mismatch repair genes (MLH1, MSH2, MSH6, and PMS2) as screening for Lynch syndrome. MSI-high and loss of MSH6 were found. Based on these results, genetic testing of MSH6 revealed a frame-shift mutation in codon 604 (c. 1806-1809delAAG/p. Glu604LeufsX5). Case 2: The patient was a younger brother of case 1. The same mutation was detected in the MSH6 gene. PMID- 26805315 TI - [A Case of Serrated Polyposis Syndrome with Early Colon Cancer]. AB - The patient was a 65-year-old man without any noteworthy medical history. A colonoscopy conducted after a positive fecal occult blood test revealed approximately 100 polyps in the large intestine. A biopsy of some these polyps revealed serrated and hyperplastic polyps, which were histologically determined to be well-differentiated adenocarcinoma. Based on these findings, a diagnosis of serrated polyposis syndrome (SPS) was made, and the patient underwent laparoscopic pancolectomy/ileoproctostomy. Histopathological analysis revealed a total of 91 lesions, out of which 15 were >=10 mm. A 30 mm lesion in the ascending colon was a well-differentiated adenocarcinoma, stage I colon cancer (T1a [sm], ly0, v0, N0, and M0). No germline mutations were found on genetic testing of the adenomatous polyposis coli (APC), mutY homolog (MUTYH), mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6), and postmeiotic segregation increased 2 (PMS2) genes. No loss of MLH1 protein expression or expression of mutated B-Raf (BRAF) V600E protein was observed in the cancer regions after immunostaining. This case is important because not only is the condition rare but also because it showed that the serrated pathway may not necessarily be the mechanism by which serrated lesions become cancerous in patients with SPS. PMID- 26805316 TI - [The Case of a Long-Surviving Patient with Colorectal Neuroendocrine Carcinoma with Invasion of the Jejunum and Lymph Node Metastases after Operation]. AB - A 44-year-old man presented to our hospital with high fever and right side ache. Laboratory data revealed the presence of inflammation. Enhanced CT of the abdomen revealed a 15 cm mass of the ascending colon, and FDG-PET showed abnormal uptake in the same site. Colonofiberscopy demonstrated an elevated lesion in the ascending colon without malignant findings in biopsies. Enema examination revealed an extrinsic compression of the ascending colon. Although the patient received antibiotic therapy, there were no signs of improvement. Therefore, right hemicolectomy with resection of the invasive lesion of the right abdominal wall and the jejunum was performed. The resected specimen showed a solid tumor, 17*11*8 cm in size, in the ascending colon. The tumor invaded the ileum. Immunohistochemical findings revealed positive staining for NSE, synaptophysin, and chromogranin A. Neuroendocrine carcinoma was thus diagnosed. CPT-11 containing chemotherapy was administered for 1 year after surgery. The patient has been free from recurrent disease for over 7 years after surgery. PMID- 26805317 TI - [A Case of Goblet Cell Carcinoid Diagnosed after Appendectomy]. AB - A man in his 60's was admitted to our hospital because of right lower abdominal pain. We diagnosed acute appendicitis with an abscess, and he was treated with laparoscopic-assisted appendectomy. The histopathological diagnosis was a goblet cell carcinoid (GCC) of the appendix. Because of the possibility of lymph node metastasis, the patient underwent laparoscopic- assisted ileo-cecum resection with lymph node dissection (D2). Metastasis was detected in one of the dissected lymph nodes. This patient has been followed-up for a year after surgery and no recurrences have been detected. PMID- 26805318 TI - [Two Cases of Colorectal Cancer with Tumor Thrombus in the Inferior Mesenteric Vein]. AB - In colorectal cancer, progression with an intravenous tumor thrombus is very rare. Here, we report 2 cases of colorectal cancer which showed a tumor thrombus in the inferior mesenteric vein (IMV). Case 1: A 69-year-old woman was admitted for the treatment of advanced rectal cancer, and underwent a low anterior resection. Six months of post-operative therapy was carried out with mFOLFOX6, but a metachronous lung metastasis was detected and a lung partial resection was performed. Case 2: A 67-year-old man was admitted for the treatment of advanced sigmoid colon cancer with simultaneous liver metastasis, and underwent a laparoscopic high anterior resection. Four courses of mFOLFOX6+bevacizumab chemotherapy were carried out after surgery, and subsequently he underwent a partial hepatectomy. In both cases IMV tumor thrombus was suspected from abdominal contrast-enhanced computed tomography (CT). Tumor thrombus filling the lumen of the IMV was confirmed on histopathological examination. Colorectal cancer with IMV tumor thrombus is a form of advanced cancer with advanced vascular invasion, and there is a high risk of simultaneous or metachronous hematogenous metastasis. Combined modality therapy should therefore be given to improve the prognosis. PMID- 26805319 TI - [Case Report of a Splenic Abscess Due to Colon Cancer]. AB - The patient was a 63-year-old man with a chief complaint of fever and abdominal pain. He was admitted with the diagnosis of splenic abscess on enhanced abdominal computed tomography. After improvement of general condition, we planned a colonoscopy. However, the symptoms were not relieved, so we decided to perform splenectomy. The operative findings included a bulky mass at the splenic flexure, which involved the spleen and the pancreatic tail. Therefore, partial colectomy, splenectomy, and distal pancreatectomy were performed. The pathological examination revealed that the splenic abscess had not developed as a direct extension of the colon cancer but the cancer spread to the splenic hilus. Surgical resection is the first choice in the therapy of splenic abscess developing from colon cancer. PMID- 26805320 TI - [A Case of Colon Cancer That Developed in the Subcutaneously Reconstructed Colon after Esophagectomy for Thoracic Esophageal Cancer]. AB - An 83-year-old man with a history of esophagectomy for thoracic esophageal cancer presented with a chief complaint of upper gastrointestinal endoscopy abnormality. Upper gastrointestinal endoscopy revealed colon cancer developing in the subcutaneously reconstructed colon, located 45 cm from the incisor tooth. Computed tomography and positron-emission tomography revealed a thickening of the wall of the reconstructed colon, a lymph node metastasis adjacent to the reconstructed colon, and no distant metastases. A partial colectomy with excision of the breastbone, rib cartilage, and the lymph node adjacent to the reconstructed colon was performed. The patient experienced a localized recurrence on postoperative day 75 and was treated with chemotherapy. The patient is alive 2 years after the diagnosis of local recurrence. PMID- 26805321 TI - [Usefulness of Transanal Decompression Tubes in Patients with Left-Sided Obstructive Colorectal Cancer]. AB - PURPOSE: The present study aimed to clarify the usefulness of the transanal decompression tube as a bridge for surgery in patients with left-sided colorectal cancer. Eight patients were recruited for this study. PATIENTS AND METHODS: We divided the patients into 2 groups: Group A included 5 patients (3 men and 2 women aged between 56 and 87 years with a mean age of 72.6 years) who underwent successful intraluminal decompression, and group B included 3 patients (3 men aged between 66 and 75 years with a mean age of 70.7 years) whose procedures were unsuccessful. We analyzed the clinical characteristics including the surgical procedure and complications, among other factors. RESULTS: Decompression periods were significantly longer in group A than in group B (p=0.0113). Rectal tumors were more prevalent in group A compared to group B. There were more patients with advanced stages (Stages IIIa and IV) in group B than in group A, as well as patients with moderately differentiated tubular adenocarcinoma. Radical surgery was performed in all group A patients. In group B, 2 patients underwent a second operation. As for postoperative complications, adhesion ileus was found in 1 group A patient, and surgical site infection in 1 group B patient. CONCLUSION: Patients with successful intraluminal decompression underwent radical surgery. In contrast, a second operation was performed in 1 patient with failed intraluminal decompression, while a stoma formed in another. PMID- 26805322 TI - [Usefulness of Metallic Stent for Left-Sided Obstructive Colon Cancer]. AB - The aim of this study was to compare the efficacy of self-expandable metallic stent (SEMS) and transanal tube as preoperative treatments for left-sided obstructive colon cancer. Forty-three patients (the SEMS group: 28 cases, the tube group: 15 cases) were included in this study. Clinicopathological data (age, sex, tumor location, depth, histological type, stage) were comparable between the 2 groups. In addition, there was no difference in intestinal decompression rate between the SEMS group and the tube group (technical success rate: 100% vs 86.7%, clinical success rate: 92.8% vs 73.3%, complication rate: 7.1% vs 0%). A significantly higher number of patients in the SEMS group underwent laparoscopic surgery because of difference of historical background. However, no significant difference was observed between the 2 groups in postoperative outcome(complication rate, hospital stay duration). SEMS insertion had several benefits compared to transanal tube placement, such as the resumption of oral intake because of rapid resolution of obstruction and easier management because SEMSs do not require washing. SEMS insertion could be a safe and effective bridge to subsequent surgery in patients with left-sided obstructive colon cancer. PMID- 26805323 TI - [Cases of Obstructive Colon Cancer for Which Elective Surgery Was Performed after Colonic Stent Placement]. AB - The present study investigated the short-term outcomes of 20 patients with obstructive colon cancer who underwent colonic stent placement as a bridge to surgery (BTS) during the 3-year period between April 2012 and March 2015. Subjects comprised 13 men and 7 women, with a mean age of 68.3 years. Placement and decompression were successfully achieved in all of the patients. Oral ingestion became possible from a mean of 2.7 days after placement. No serious complications associated with placement were encountered. Total colonoscopy was performed after placement in 17 patients (85%), and independent advanced cancer was seen in the proximal portion of the colon in 1 patient. Elective surgery was performed for all of the patients after placement. Excluding the 2 patients for whom preoperative chemotherapy or treatment of another disease was prioritized, the mean interval to surgery for the remaining 18 patients was 23.2 days. The operative procedure performed was laparoscopic surgery in 8 patients (40%). Although minor leakage (n=1) and abdominal wall abscess (n=1) were observed as postoperative complications, the patients generally had an uneventful course. Colonic stent placement for obstructive colon cancer is relatively easy and safe, and may be considered as an effective treatment method that enables favorable intestinal decompression preoperatively and one-stage resection. PMID- 26805324 TI - [Efficacy of Postoperative Chemotherapy in Stage IV Colorectal Cancer with Perforation]. AB - The clinical outcome and efficacy of postoperative chemotherapy in patients with Stage IV colorectal cancer with perforation were investigated. We compared the clinical outcomes between 11 patients with Stage IV colorectal cancer (perforation group), who underwent emergency surgery for colonic perforation between September 2005 and March 2012, and 22 matched patients (matching group) who underwent elective colorectal surgery during the same period. The colostomy rate in the perforation group was significantly higher than that of the matching group: patients with perforation received stoma construction surgery more frequently (p<0.01). Seven patients (64%) in the perforation group received postoperative chemotherapy, while 20 patients (91%) in the matching group received chemotherapy (p=0.15). Oxaliplatin-based chemotherapy was administered to all patients in both groups. There was no difference in the median relative dose intensity of oxaliplatin between these groups (p=0.37). No significant difference was observed between the cumulative 3-year overall survival rate in the perforation group and that of the matching group (35% and 54%, respectively; p=0.35). Moreover, the 3-year overall survival rates of patients who received oxaliplatin-based chemotherapy were 51%in the perforation group and 57% in the matching group (p=0.74). Our results suggest that postoperative oxaliplatin-based chemotherapy may improve the prognosis of patients with Stage IV colorectal cancer with perforation. PMID- 26805325 TI - [Problems in the Treatment of Stage III Colorectal Cancer with Perforation]. AB - We retrospectively investigated clinical outcome and treatment strategies in Stage IIIcolorectal cancer patients who underwent emergency surgery because of tumor-related perforation. We compared the clinical outcome of 6 patients (perforation group) who underwent emergency surgery for colonic perforation due to Stage III colorectal cancer with 12 matched patients (matching group) who underwent elective colorectal surgery, between April 1998 and March 2012. Patients in the perforation group underwent colostomy procedures more frequently (p=0.02), had longer operative times (p=0.02), and more bleeding (p=0.04) than those in the matching group. There was no significant difference between the groups in terms of the introduction rate of chemotherapy, recurrence rate, or recurrence pattern. The 3-year disease-free survival rate was 44% in the perforation group and 81% in the matching group, resulting in no significant differences between these groups (p=0.28). The 3-year disease-free survival rates in the perforation and the matching groups were 44% and 81%, respectively (p=0.07). The 3-year overall survival rates in the perforation and the matching groups were 17% and 81%, respectively (p<0.01). The 3-year overall survival rate of patients who received adjuvant chemotherapy was 50% in the perforation group and 88%in the matching group (p=0.03). We concluded that patients with perforated Stage III colorectal cancer had a significantly poorer prognosis compared with patients with non-perforated Stage III colorectal cancer. PMID- 26805326 TI - [A Case of Bladder Adenocarcinoma with Rectal Metastasis]. AB - A 77 year-old man with asymptomatic microscopic hematuria underwent a cystoscopic examination, which identified a broad-based papillary tumor at the cervix of the bladder. Adenocarcinoma was detected in the biopsy specimen. MRI and CT examination showed a huge papillary tumor of the bladder invading the inner lobe of the prostate. In addition, the wall of the lower rectum exhibited thickening with enlargement of the regional lymph nodes. Endoscopy disclosed a hemi-circular rectal tumor and pathological examination revealed adenocarcinoma, the profile of which was similar to the bladder tumor. The levels of CEA and CA19-9 were 5.3 ng/mL and 39 U/mL, respectively. A differential diagnosis considering bladder cancer, rectal cancer, or both was necessary before planning a treatment strategy. Since both tumors were judged to be resectable, total pelvic exenteration was carried out. Through detailed postoperative pathological examinations, it was concluded that this tumor was of bladder origin and it invaded the prostate along with metastasis to the rectum. Adenocarcinoma of the bladder is extremely rare and exhibits aggressive behavior. PMID- 26805327 TI - [A Case of Small Intestinal Metastases from Renal Cell Carcinoma with Massive Bleeding]. AB - A 66-year-old man underwent laparoscopic right nephrectomy for renal cell carcinoma (T2b, N0, M1, clear cell, Grade 3). He was treated with targeted therapy for lung metastases after nephrectomy. Despite the targeted therapy, he was paralyzed in the lower half of the body due to the spinal metastases. Therefore, an osteoplastic laminectomy and domelaminectomy for the spinal metastases was performed. The FDG-PET examination, which was performed after the operation, revealed lung, liver, bone, and small intestinal metastases. After a while, he suffered from continuous massive melena. Double balloon enteroscopy revealed a hemorrhagic tumor in the small intestine, and an emergency operation was performed. A partial resection of the small intestine was performed for the 3 tumors. The histopathological diagnosis was small intestinal metastasis from renal cell carcinoma. It is well known that renal cell carcinoma often develops metastases to the lung, bone, and liver. However, small intestinal metastasis from renal cell carcinoma is rare. Although small intestinal metastasis from renal cell carcinoma often accompanies metastases to other organs, a palliative operation might improve the quality of life in patients with symptomatic tumors. PMID- 26805328 TI - [Repeated Pancreatic Resections with Parenchymal Preservation for Pancreatic Metastases of Renal Cell Carcinoma--Report of a Case]. AB - A 51-year-old man underwent right nephrectomy for renal cell carcinoma. Six months later, a solitary metastatic tumor was detected in the pancreatic tail and he underwent distal pancreatectomy and splenectomy. One year and 6 months after the initial resection, a solitary metastatic tumor was detected in the pancreas head, and he underwent partial pancreatectomy. A solitary metastatic tumor was detected again in the remnant pancreatic body 3 years and 10 months after the initial resection. Partial resection of the distal part of the remnant pancreas was performed. The patient remains alive and well with no evidence of remnant disease 4 years after the initial resection. PMID- 26805329 TI - [A Case of Anorectal Amelanotic Malignant Melanoma]. AB - We report a case of primary anorectal amelanotic malignant melanoma (MM), treated with a laparoscopic abdominoperineal resection (APR). A 75-year-old woman was referred to our hospital because of anal bleeding and pain. A finger-tip sized, dark reddish tumor, which protruded from her anus, was observed. After a tumor biopsy, the diagnosis was MM. No cutaneous pigmented regions were observed, and distant metastases and regional lymphadenopathy were not detected by computed tomography and magnetic resonance imaging. Therefore, we performed laparoscopic APR in order to relieve her symptoms. The resected specimen showed a partially pigmented tumor with a diameter of 6.0*4.1 cm in the anorectal junction. Histopathological examination of the specimen showed an amelanotic MM (negative for melanin pigmentation, and positive for HMB-45, Melan-A, and S-100). The post operative course was uneventful, and we could not find any obvious evidence of recurrence of the disease 11 months after surgery. The prognosis of anorectal MM is extremely poor, thus a less invasive surgical procedure is recommended for treatment of anorectal MM. Laparoscopic APR is useful for treating anorectal MM due to its minimally invasive nature. PMID- 26805330 TI - [A Case of Demonstrating the Difficulties in Deciding How to Manage the Clinical Results after Rectal Resection]. AB - It is important in the clinical setting to integrate all of the findings when diagnosing and making treatment decisions. We report a case of particular interest for managing cancer patients. A 69-year-old man underwent endoscopic resection for an Rb rectal tumor. The tumor showed a positive vertical margin and required laparoscopy-assisted super low anterior resection with ileostomy for histopathological stage Irectal cancer. His postoperative course was uneventful. The follow-up computed tomography (CT) scan revealed a tumor locating close to the left common iliac artery. Although positron emission tomography (PET) showed 18F-fluorodeoxyglucose (FDG) accumulation in the tumor, none of the other clinical findings indicated a recurrence of rectal cancer. FDG is not specific to malignant neoplasias, but the location of the tumor and the FDG uptake suggested the possibility of malignancy. No other tests found any evidence of a recurrence. Tumor resection was performed concurrently with ileostomy closure. Histopathology demonstrated it was an asymptomatic abscess in a lymph node. Tumor recurrence and metastases have to be kept in mind even if the primary lesion is in an early stage. This case shows the difficulty in deciding how to manage patients when clinical results are not consistent, especially in cases needing surgical procedures. PMID- 26805331 TI - [A Case of Pelvic Schwannoma, Mimicking Metastasis of Rectal Carcinoma]. AB - INTRODUCTION: Schwannoma in the lateral lymph node region is extremely rare; however, this tumor has been reported to have relatively high SUV on PET-CT, suggestive of malignancy. CASE: A 67-year-old man with advanced lower rectal cancer had a small nodule with FDG accumulation (SUVmax 2.6) near the left internal iliac artery. His preoperative diagnosis was rectal cancer with lateral lymph node metastasis. He underwent super-low anterior resection with lateral lymph node dissection. Histopathological examination was conclusive for pT3 (A), with an Rt263D lymph node metastasis. Interestingly, a schwannoma was detected among the harvested lymph nodes. CONCLUSION: Although rectal cancer is known to involve pelvic lymph nodes, the role of preoperative diagnosis with FDG-PET is unclear. We should consider that schwannoma is associated with slight elevation of SUVmax and it may mimic lymph node metastasis. PMID- 26805332 TI - [A Case of MALT Lymphoma of the Rectum Treated with Intersphincteric Resection (ISR)]. AB - A 60-year-old woman visited a local hospital complaining of melena. On colonoscopy, she was found to have 2 tumors in the lower rectum, each of approximately 10 mm in diameter. A biopsy of the tumors indicated MALT lymphoma, and the patient was referred to our hospital. We performed intersphincteric resection (ISR) with lymph node dissection according to the guidelines for the treatment of rectal cancer for 2 reasons. One reason was that eradication therapy for Helicobacter pylori was not effective in this case, and we needed to obtain an accurate histopathological diagnosis as to whether the patient had diffuse large B cell lymphoma (DLBCL). The other reason was that it was localized disease in the rectum, and that curative resection could be performed. MALT lymphoma of the rectum occurs frequently in the lower rectum and has a relatively good prognosis. It is important to consider the quality of life when selecting an operative method. ISR is thought to be a good option. PMID- 26805333 TI - [A Case of Rectal Villous Tumor Detected with Heart Failure and Electrolyte Imbalance]. AB - A 74-year-old woman presented to our emergency department with a chief complaint of appetite loss, and already diagnosed dehydration and heart failure. After hospitalization, the signs of heart failure were improved with liquid supplementation and electrolyte revision. At admission, computed tomography incidentally detected a rectal tumor. She underwent colonography, which revealed a huge villous tumor in the rectum. Based on the result of the initial biopsy, it was classified as a group 4 tumor, but additional biopsy of specimens obtained from 6 places led to a diagnosis of group 5 tumor. Then, we performed laparoscopic super-low anterior resection and made an ileal stoma. The electrolyte imbalance was improved and did not recur after the operation. In this case, the electrolyte imbalance caused by the huge villous tumor was electrolyte depletion syndrome (EDS). PMID- 26805334 TI - [Repeated Insertion of Self-Expandable Metallic Stents as a Palliative Therapy for Unresectable Colorectal Cancer]. AB - A 62-year-old man was admitted to our hospital for malignant rectal stricture due to metastatic rectal cancer. He underwent placement of a self-expandable metallic stent (SEMS). After the administration of 5 courses of FOLFOX4 with bevacizumab, chemotherapy-induced tumor shrinkage led to migration of the SEMS, which was removed immediately without complication. After 10 courses of chemotherapy, he had to discontinue the treatment due to liver failure resulting from tumor progression. Another SEMS was successfully inserted for the progression of rectal stenosis. The patient's QOL was maintained to the end with the SEMS. This case suggests that although it is essential to pay attention to possible complications, SEMS insertion is a very useful procedure for palliative therapy. PMID- 26805335 TI - [Palliative Care for Rectal Cancer Complicated with Gastric Cancer]. AB - Medical advancements have led to an increase in the number of elderly people. However, standard treatments may sometimes be difficult to use in elderly people. Here, we report the case of an elderly patient with rectal and gastric cancer who refused radical surgery. The patient was an 83-year-old man who had type-2 diabetes, hypertension, hyperuricemia, mitral valve regurgitation, and mild dementia. Furthermore, he was blind in both eyes owing to glaucoma. He first visited our hospital in 2005. In 2010, he was diagnosed with anemia, but he refused a thorough examination; however, he did consent to take iron supplements. In July 2011, he consulted our hospital for symptoms of frequent diarrhea, and agreed to an examination. After colonoscopy, he was diagnosed with rectal cancer that was becoming obstructive. There were no metastases to other organs, but he was also diagnosed with gastric cancer. As he and his family refused radical surgery, a stoma was constructed. After the operation, he received palliative care but died in September 2013. PMID- 26805336 TI - [A Case of Local Recurrence and Lung Metastasis from a Rectal Cancer Treated with Systemic Chemotherapy and Cyberknife]. AB - A 73-year-old man underwent abdominoperineal resection for a rectal cancer. He developed a hip pain 3 years and 6 months after the surgery. A CT scan revealed a local recurrence in the perineum and multiple lung metastases in the bilateral lung. He received systemic chemotherapy consisting of XELOX with bevacizumab. Thereafter, the hip pain was slightly relieved. The hip pain worsened 1 year and 6 months after the recurrence. The border between the perineal tumor and skin was very narrow, and conventional radiation therapy could cause a perineal skin necrosis and subsequent poor wound healing. Therefore, we selected a Cyberknife treatment. The hip pain was relieved and a CT scan showed a reduction of the perineal tumor's size after the Cyberknife treatment. A Cyberknife treatment may be effective and promising as palliation for patients with local recurrence of rectal cancer. PMID- 26805337 TI - [Super-Elderly Patient with Recurrent Rectal Cancer with Liver Metastases Effectively Treated with Capecitabine plus Bevacizumab Chemotherapy--Report of a Case]. AB - The safety and feasibility of chemotherapy for super-elderly patients (over 85 years old) has not been clarified yet. We report an extremely aged patient with recurrent rectal cancer that was successfully treated with capecitabine plus bevacizumab chemotherapy. An 85-year-old-woman underwent a Hartmann procedure for rectal cancer. Nine months after surgery, tumor markers were elevated. CT and MRI revealed liver metastases in S5 and S7. We administered capecitabine plus bevacizumab chemotherapy. Tumor makers were normalized after 2 courses, and the liver metastases disappeared after 6 courses. Although Grade 1 hypertension developed, no other adverse event occurred. Chemotherapy has been safely performed for 20 courses. The patient's PS score has been maintained at 0, and she has been under treatment as an outpatient. We suggest that capecitabine plus bevacizumab chemotherapy is an effective regimen for extremely aged patients with recurrent colorectal cancer. PMID- 26805338 TI - [Complete Response to Chemotherapy after Resection of Rectal Cancer with Virchow's Lymph Node Metastasis]. AB - A 62-year-old woman was admitted to our hospital because of bloody stool. Colonoscopy revealed stenosis by a type 2 tumor of the recto-sigmoid colon. A biopsy specimen contained moderately differentiated adenocarcinoma. Thoraco abdominal computed tomography (CT) showed liver metastasis (S7, 10 mm) and enlargement of Virchow's lymph node (17 mm) and several para-aortic lymph nodes (15 mm on average). Because of oozing from the tumor and severe stenosis of the recto-sigmoid colon, we performed laparoscopic-assisted high anterior resection of the primary lesion. After surgery, 3 courses of mFOLFOX6, 20 courses of mFOLFOX6 plus bevacizumab, and 5 courses of infusional 5-FU plus Leucovorin plus bevacizumab were administered. Thoraco-abdominal CT demonstrated complete response to the 1 year 2 months of chemotherapy. The patient has been alive without relapse for 2 years after surgery. PMID- 26805339 TI - [A Case That in Most Part of the Metastatic Liver Tumor Fell into Spontaneous Necrosis after Surgery of Rectal Cancer]. AB - We present a case of a 74-year-old woman treated with maintenance dialysis for chronic renal failure. She had undergone intravascular treatment of lower limb arteriosclerosis obliterans 3 times. Low anterior resection was performed for rectal cancer StageII, but adjuvant chemotherapy was not administered after the operation. S5/S6 partial hepatectomy was performed after confirming a liver metastatic recurrence 7 months after the first operation. Tumor pathology examination of the resected specimen revealed necrosis in most parts of the specimen. Residual primary lesion similar to adenocarcinoma tissue was found only in a small part of the specimen. Artery wall embolism and recanalization image with cholesterol crystals indicated a Grison's lesion, which was considered to have likely developed into tumor necrosis from the embolization. Spontaneous regression of a malignant tumor is a rare condition found 1 case in 6-10 ten thousand cases. In hepatocellular carcinoma, secondary tumor infarction from tumor invasion and tumor thrombus may occur. The present case was a metastatic liver cancer, in which the cholesterol crystal embolism possibly reached the tumor necrosis. The suggested cause of the cholesterol crystal embolism in this case was intravascular treatment related. PMID- 26805340 TI - [Recurrence of Rectal Cancer with Submucosal Invasion in the Bone and Lymph Nodes 89 Months after Surgery--A Case Report]. AB - A woman in her 60s showed positive results on a fecal occult blood test and consulted her doctor. Early-stage cancer of the lower rectum was diagnosed, and a transanal local excision was performed. Histopathological examination revealed that the depth of submucosal invasion was ?1,000 mm, and the submucosal invasive part of the tumor was a poorly differentiated adenocarcinoma. Therefore, she was referred to our hospital for additional resection. Intersphincteric resection was performed 11 months after the initial operation. The cancer stage was T1N0M0, Stage I(UICC 7th edition), and the cancer did not recur. The patient visited our hospital again, 78 months after the additional resection, because of left hip joint pain. Positron-emission tomography revealed fluorodeoxyglucose uptake in the left acetabulum, para-aortic lymph nodes, and left external iliac lymph nodes; these findings indicated recurrence of the rectal cancer. The patient received radiation therapy (57 Gy) and FOLFIRI; bevacizumab was added from the third course onward. The therapy reduced the size of the tumor recurrence in the bone. This was a rare case of rectal cancer with submucosal invasion that showed recurrence in the bone and lymph nodes 78 months after the additional resection. PMID- 26805341 TI - [A Case of Rectal Carcinoma with Recurrence around the Drainage Site Complicated by Fournier's Gangrene]. AB - A 71-year-old woman diagnosed with Fournier's gangrene caused by penetration of a rectal carcinoma was referred to our hospital. Emergency drainage and sigmoid colostomy were performed. Pathological examination of a biopsy sample showed moderately differentiated tubular adenocarcinoma. Abdominoperineal resection with bilateral salpingo-oophorectomy and hysterectomy was performed with curative intent after 4 courses of chemotherapy with S-1 and oxaliplatin. The postoperative pathological diagnosis was StageII (pT4bN0M0). The patient received tegafur/uracil and Leucovorin as adjuvant chemotherapy. Seven months after the curative operation, partial pneumonectomy was performed for the recurrence of the rectal carcinoma in the right lung. Eight months after pneumonectomy, recurrent tumors were observed in the right lung and subcutaneous fat layer of the right buttock along the drainage site. The tumor in the right buttock was excised along with part of the gluteus maximus, and partial pneumonectomy was then performed. Three years and 6 months after the emergency drainage, the patient is alive with no evidence of recurrence. After drainage for rectal carcinoma complicated by Fournier's gangrene, the possibility of recurrence around the drainage site should be considered. PMID- 26805342 TI - [Laparoscopic Surgery for Adult Intussusception Due to Rectal Cancer--A Case Report]. AB - An 87-year-old woman with the chief complaint of bloody stool was referred to our hospital from an institution for the aged. The abdomen was soft and flat, and a tumor was not palpable on digital rectal examination. Tumor markers were within normal ranges. Abdominal enhanced CT scan showed a multiple concentric ring sign at the rectum. Colonoscopic and barium examination led to a diagnosis of rectal intussusception due to rectal cancer. We first tried to reposition it preoperatively, but it was impossible. She fortunately had no symptoms of ileus; therefore, we chose to perform laparoscopic surgery. We achieved the reposition intraoperatively and performed Hartmann's operation with D2 lymph node dissection because she was a very elderly patient with high-risk comorbidities. The pathological diagnosis was as follows: RS, 40*40 mm, type 2, tub2, pT3 (SS), pN0, ly0, v0, pStageII, R0, Cur A. Adult intussusception due to rectal cancer is extremely rare. We report that in this case that laparoscopic surgery was possible, along with a review of the relevant literature. PMID- 26805343 TI - [A Case of Adult Invagination Caused by Rectal Cancer]. AB - An 87-year-old man visited our hospital with a chief complaint of melena. Invagination caused by rectal cancer or sigmoid colon cancer was suspected as a result of physical and radiological examinations. Since there were no subjective symptoms, laparoscopic surgery was planned electively. As an operative finding, a tumor was found in the rectosigmoid colon and caused invagination. The invagination was released during an operation, and high anterior resection with D3 dissection was performed laparoscopically. The operation time was 108 minutes and the amount of blood loss was 22 mL. Although anastomotic leakage occurred as a postoperative complication, recovery was achieved conservatively by percutaneous drainage. In many cases, invagination of adults is caused by a solid tumor such as bowel carcinoma, which commonly occurs at the cecum or sigmoid colon. Although invagination of the rectosigmoid colon fixed to the retroperitoneum is relatively rare, the fragility of the supporting tissues in the pelvis accompanied by aging is considered to be a cause. In cases of a large tumor occupying the lumen of the intestine, appropriate preoperative diagnosis is needed and the method of operation should be chosen carefully. PMID- 26805344 TI - [Mesorectal Lymph Node Metastasis Arising from Rectal Invasion by an Ovarian Cancer--A Case Report]. AB - A 58-year-old woman presenting with abdominal distension was diagnosed with a tumor in the right ovary. A chest-abdominal-pelvic computed tomography scan revealed multiple lung metastases, multiple liver metastases, and peritoneal dissemination. Invasion of the rectum by peritoneal dissemination of the Douglas' pouch was suspected. She was diagnosed with Stage IV right ovarian cancer and was treated with preoperative chemotherapy. After chemotherapy, debulking surgery of the abdominal cavity (total hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy, and Hartmann's procedure) was performed. Because there was swelling observed in multiple mesorectal lymph nodes, lymph node dissection was performed based on methods used for rectal cancer surgery. Postoperative histopathological examination revealed multiple mesorectal lymph node metastases arising from ovarian cancer. We suggest that mesorectal lymph node dissection be considered a part of debulking surgery for ovarian cancers that have invaded the rectum. PMID- 26805345 TI - [Three Cases of Stage IV Low Rectal Cancer with Lateral Pelvic Lymph Node Metastasis]. AB - Case 1: A 61-year-old man who had a diagnosis of low rectal cancer with lateral pelvic lymph node (LPLN) metastasis and multiple liver metastases underwent low anterior resection with LPLN dissection. The initial surgery was followed by chemotherapy, and then an extended right hepatectomy with partial resection of the liver was performed. Subsequently, a lung metastasis was detected, and the lung was partially resected. The patient was alive 9 years and 6 months after the initial operation. Case 2: A 53-year-old man had a diagnosis of low rectal cancer. After 5 courses of mFOLFOX6 plus bevacizumab, he underwent low anterior resection with LPLN dissection and resection of the peritoneal metastasis. The patient was alive 6 years and 3 months after the surgery without any signs of recurrence. Case 3: A 48-year-old man had a diagnosis of low rectal cancer and multiple liver metastases. He underwent low anterior resection with LPLN dissection and right hepatic lobectomy. He subsequently showed liver and lung metastases. The patient received systemic chemotherapy, and is alive with recurrent disease. We report 3 cases of Stage IV low rectal cancer with LPLN metastasis, and propose that LPLN dissection is important as a part of R0 resection for Stage IV low rectal cancer. PMID- 26805346 TI - [Clinical Significance of Lateral Lymph Node Dissection for Stage IV Low Rectal Cancer]. AB - We reviewed the clinical records of 81 patients with stage IV low rectal carcinoma (LRC) (25 Cur B surgeries and 56 Cur C surgeries) to evaluate the effectiveness of lateral lymph node dissection (LLND) by comparing the treatment outcomes with those of patients with stage III LRC. Mesenteric lymph node metastasis was a risk factor for local recurrence in a multivariate analysis. There were no significant differences in the frequency of lateral node metastasis, local recurrence rate, or prognosis between Cur B and stage III LRC patients. We suggest that LLND effectively improves prognosis as well as local control in Cur B patients. In Cur C patients, prognosis was poor regardless of lateral node metastasis. However, in patients with lateral node metastasis, there were no significant differences in between the Cur C (25.0%), Cur B, and stage III groups, suggesting that LLND improves local control in Cur C patients with lateral node metastasis. Although the local recurrence rate was high (71.4%) in Cur C patients without lateral node metastasis, fewer lateral lymph nodes were harvested in these patients than in those with lateral node metastasis. Our results indicate that further examination of the local control effects of LLND in Cur C patients is necessary. PMID- 26805347 TI - [A Case of Recurrence of Rectal Cancer with Para-Aortic Lymph Node Metastases Successfully Resected Resulting in Long Term Survival]. AB - Laparoscopy-assisted low anterior resection (Japanese D3 lymph node dissection) was performed to treat a 68-year-old man for rectal cancer. Microscopically, the resected specimen was diagnosed as a moderately differentiated adenocarcinoma and the final stage was considered as pT3, pN1, cM0, pStage IIIa. He was administered capecitabine for 6 months as adjuvant chemotherapy. Then, enlarged para-aortic lymph nodes, indicated by follow up CT at 1 year and 11 months postoperatively developed behind the left renal artery. FDG accumulated in it, consistent with the CT images. Para-aortic lymph node dissection was performed after the diagnosis of solitary lymph node metastases. Microscopically, the resected lymph nodes showed features similar to the primary lesion. He is doing well without recurrence for 4 year and 6 months, without any adjuvant chemotherapy. Para aortic lymph node metastases are frequently associated with other distant metastases; if not, a complete cure may be possible by curative resection for solitary metastases. PMID- 26805348 TI - [Two Cases of Pathological Complete Response with Neoadjuvant Therapy for Advanced Rectal Cancer]. AB - We report the cases of 2 patients with advanced rectal cancer who achieved pathological complete response to treatment with preoperative therapy. Case 1 was a 72-year-old man diagnosed with cT3N1M0 advanced rectal cancer. Neoadjuvant chemoradiotherapy with S-1 (120 mg/day) and radiation (50 Gy/25 Fr) was administered. Eight weeks after the last chemoradiation therapy, we performed laparoscopic Hartmann's operation. Case 2 was a 59-year-old man diagnosed with cT4aN0M0 advanced rectal cancer. He was treated with XELOX plus bevacizumab as neoadjuvant chemotherapy. Four weeks after 4 courses of treatment, he underwent laparoscopic Mile's operation. Neoadjuvant therapy was performed without any complications, and a pathological complete response was achieved in both patients. These cases demonstrated that neoadjuvant therapy can be a promising option for locally advanced rectal cancer. PMID- 26805349 TI - [A Case of Locally Advanced Rectal Cancer with a Pathological Complete Response to Preoperative Chemoradiotherapy]. AB - A 61-year-old woman presented with the chief complaint of melena. She was diagnosed with rectal cancer via colonoscopy. Computed tomography (CT) revealed a rectal cancer with wall thickening, accompanied by several regional lymph node metastases with no distant metastasis. The tumor stage was cT3, cN2a, cM0 according to the TNM Classification of Malignant Tumors (7th Edition, UICC). Preoperative chemoradiotherapy (CRT) (UFT 400 mg/day tegafur-uracil and 75 mg/day Leucovorin; 1.8 Gy in 25 fractions, total 45 Gy) was administered. Eight weeks after CRT, laparoscopy-assisted low anterior resection was performed. A pathological examination revealed that both the primary site and regional lymph nodes had no residual cancer cells, and a diagnosis of pathological complete response was made. The patient has been disease-free for 4 years since the operation. We report a case of rectal cancer that was successfully treated via preoperative CRT. This case may aid the development of a standard therapy for advanced rectal cancer. PMID- 26805350 TI - [A Case of Anal Canal Carcinoma with Inguinal Lymph Node Metastasis Treated with Laparoscopic Abdominoperineal Resection]. AB - We report a case of anal canal cancer with inguinal lymph node metastasis treated with laparoscopic abdominoperineal resection combined with inguinal lymph node dissection. A 52-year-old woman was diagnosed with anal squamous carcinoma after excision of an anal canal tumor. Further examination revealed right inguinal lymph node metastasis. Chemoradiotherapy was administered but was discontinued because of serious adverse events. We therefore performed laparoscopic abdominoperineal resection combined with inguinal lymph node dissection. The pathological findings revealed residual squamous cell carcinoma at the lymphatic vessels in the rectal wall and lymph nodes, including the right inguinal region. Therapeutic effect of Grade 1a was achieved in spite of interruption of the chemoradiotherapy. She was discharged 17 days after the operation, and no recurrence was observed for 11 months. Radical resection was performed for the anal canal squamous cell carcinoma with the metastasis to the right inguinal lymph node, even after interruption of the chemoradiotherapy. PMID- 26805351 TI - [A Case of Squamous Cell Carcinoma of the Anal Canal with a Perianal Abscess]. AB - A 72-year-old female patient was referred to our department because she felt pain at the anus with pus discharge. Physical examination revealed a tumor on the left side of the anus, and a subcutaneous induration near the tumor. Abdominal CT scan revealed an irregularly shaped tumor with abscess formation. There were no enlarged lymph nodes or distant metastasis. Anal canal carcinoma (cStage II) with a complication of perianal abscess was suspected, so we performed surgical incision and drainage. A biopsy of the tumor led to the diagnosis of squamous cell carcinoma. However, because surgical drainage alone was not effective for treatment of the abscess, colostomy of the sigmoid colon was carried out 14 days after admission. After chemoradiation therapy (5-FU 800 mg/m2/day on days 1-4 and 29-32, mitomycin C [MMC] 10 mg/m2 on days 1 and 29, and radiation with a total dose 54 Gy), the tumor disappeared completely, considered to be a complete response. Twenty months after chemoradiation, there were no signs of recurrence. PMID- 26805352 TI - [A Case of Anal Canal Cancer Treated by Abdominoperineal Resection in a 100-Year Old Woman]. AB - A 100-year-old woman visited our hospital because of erosion and bleeding in her anal region in January 2014. Computed tomography scans revealed the presence of a tumor in the anal canal, which caused a considerable amount of pain and bleeding over the next 4 months. Accordingly, immediate surgical intervention was considered necessary to provide local control. Therefore, we decided to perform abdominoperitoneal resection after consultation with her family. The operation was successfully completed, and histopathological examination indicated a diagnosis of adenocarcinoma of the anal canal. The postoperative course was almost uneventful, and the patient was discharged on the 23rd post-operative day. There are some cases reported in Japan where laparotomy was performed for patients over 100 years of age, but none of them were treated surgically for anal canal cancer. We suggest that elective surgical intervention can be an effective option for the treatment of abdominal and pelvic malignancies even in patients of an extremely advanced age. PMID- 26805353 TI - [Conversion Therapy of Initially Unresectable Rectal Cancer with Perforation via FOLFOX4 Chemotherapy]. AB - We describe a case of perforated rectal cancer that became curatively resectable after FOLFOX4 chemotherapy. An 81- year-old woman was transferred to our hospital with a diagnosis of bowel perforation. She underwent emergency transverse colostomy, peritoneal lavage, and the insertion of indwelling drainage tubes, because the perforated rectal cancer was considered unresectable. After recuperation, she received chemotherapy consisting of FOLFOX4 and bevacizumab. Owing to a good response to the treatment after 4 months, rectal resection was achieved curatively. Wound dehiscence occurred as a postoperative complication. The patient chose not to receive adjuvant chemotherapy. Currently, she has been alive for more than 1 year 3 months after resection without recurrence. PMID- 26805354 TI - [A Case of Locally Advanced Rectal Cancer Curatively Resected Following Chemoradiotherapy]. AB - A man in his 70s was referred to our hospital with anorexia, weight loss, and constipation. After examination by computed tomography (CT), magnetic resonance imaging (MRI), and colonoscopy, he was diagnosed as having a locally advanced rectal cancer with abscess formation. Because CT and MRI indicated that the tumor had invaded the seminal vesicle, prostate, and sacrum, we diagnosed it as an unresectable tumor. We treated the abscesses around the tumor by sigmoid colostomy with administration of antibiotics. After control of the infection, the patient received systemic chemotherapy with capecitabine/oxaliplatin (XELOX) plus bevacizumab (BV). After the 5th courses of XELOX plus BV, the primary tumor showed a tendency to shrink, but invasion to the neighboring organs was still seen. Therefore, we treated him with chemoradiotherapy (CRT) using S-1. After completion of CRT with no significant adverse effects, the tumor invasion to the neighboring organs disappeared, and we performed a low anterior resection 9 weeks later. Pathological findings revealed that the tumor had shrunk remarkably and it was resected curatively, although a few tumor cells remained in the subserosal layer of the ulcerative scar caused by the CRT. His postoperative course was uneventful, and he underwent adjuvant chemotherapy with S-1 for 3 months after discharge. To date, no disease recurrence has been detected. We report a case of locally advanced rectal cancer, which was curatively resected following chemoradiotherapy, along with a short literature review. PMID- 26805355 TI - [A Case of Rectal Cancer Completely Resected after Successful Treatment with Irinotecan plus Cetuximab-Induced Interstitial Pneumonia with Steroid Pulse Therapy]. AB - We report of a 74-year-old man with advanced rectal cancer invading the small intestine and bladder. Initially, 3 courses of neoadjuvant chemotherapy with FOLFIRI and cetuximab were administered. At the beginning of the 4 course, the patient experienced fever and dyspnea. Chest radiography and computed tomography showed ground-grass opacities in both lungs. He was diagnosed with interstitial pneumonia induced by irinotecan or cetuximab. Steroid pulse therapy consisting of methyl-prednisolone (1,000 mg/day; 3 days) with respiratory assist resulted in significant improvement, and prednisolone was continued while reducing the dose gradually. He stopped the medicine on the 106th day from the first treatment, and underwent the R0 operation on the 113th day. We report for the first time a case of interstitial pneumonia occurring after neoadjuvant chemotherapy for advanced rectal cancer that was successfully resected after treatment. PMID- 26805356 TI - [Total Pelvic Exenteration for Local Recurrence of Rectal Cancer Appearing 12 Years after Curative Operation--A Case Report]. AB - A 49-year-old man had undergone Hartmann's operation for rectal cancer in August 2002. The disease stage (TNM 7th) was T3, N1, M0, Stage IIIB. He was treated with UFT and Krestin for a year as adjuvant chemotherapy. No recurrence had been detected after the surgery. In July 2014, he presented with symptoms of acute renal failure. A CT scan showed bilateral hydronephrosis and a pelvic tumor between the urinary bladder and rectum. The pathological diagnosis based on biopsy specimens was adenocarcinoma. Because immunostaining studies of the tumor biopsy specimen revealed that CK20, CEA, CA19-9, and p53 were positive and CK7 and PSA were negative, this pelvic tumor was diagnosed as a local recurrence of rectal cancer. Total pelvic exenteration and ileal conduit urinary diversion were carried out for the recurrent tumor with curative intent. The reported recurrence rate of Stage III colorectal cancer 5 years after the initial curative operation is 0.67%. Local recurrence of rectal cancer 12 years after the initial operation is quite rare. Immunostaining is helpful to discriminate between rectal cancer and a tumor of the urinary organs. It is important to consider that recurrence of rectal cancer might still occur a long time after the initial operation. PMID- 26805357 TI - [A Case of Long-Term Survival after Resection of Liver and Adrenal Metastases from Rectal Cancer]. AB - A 72-year-old man underwent Miles' operation for rectal cancer. Histological findings showed moderately differentiated adenocarcinoma, a, ly0, v1, n0, stage II(ly0, v1). Five months later, left lateral segmentectomy and left adrenalectomy were performed owing to the metastasis of the rectal cancer to the liver and adrenal glands. Two years after these operations, left nephrectomy was performed for retroperitoneal recurrence around the left kidney. All resected specimens showed metastatic adenocarcinoma derived from the rectal cancer. No recurrence has been detected in the 4 years since the left nephrectomy. Aggressive resection of well-controlled metastatic lesions including those in the adrenal glands is recommended. PMID- 26805358 TI - [A Case of Gastric and Pancreatic Cancer Resected with Curative Intent while Preserving Organ Function]. AB - A 57-year-old woman was diagnosed with a pancreatic tumor. Abdominal computed tomography showed cStage IVa pancreatic cancer with a 20*16 mm tumor near the base of the celiac artery. Since the tumor contacted the SMA at an angle of 90 degrees, it was judged as a borderline resectable tumor. In addition, cStage IB gastric cancer was found in the corpus ventriculi. Since the patient had a respiratory complication, a distal pancreatectomy with celiac axis resection in combination with a total gastrectomy was considered too aggressive for this patient. Therefore, she received chemoradiotherapy prior to the surgery. Distal pancreatectomy with D2 lymphadenectomy and subtotal gastrectomy with lower left phrenic artery preservation was performed. This case involved a considerable extension of the disease and radical surgery; however, currently the patient's prognosis and QOL are good. PMID- 26805359 TI - [Three Resected Cases of Metachronous Pancreatic Cancer Successfully Treated with Repeated Pancreatectomy]. AB - Repeated pancreatectomy for metachronous pancreatic cancer has rarely been reported. We report 3 cases with metachronous pancreatic ductal carcinoma that developed after pancreatectomy for the first pancreatic cancer. They were successfully resected by removal of the remnant pancreas. In all 3 cases, the cancers in the remnant pancreas were treated with repeated pancreatectomy. The histological margin of the first pancreatic resection was cancer-free in all the cases. Furthermore, the second cancer tissue contained carcinoma lesions in situ adjacent to invasive ductal carcinoma. Based on these findings, the 3 patients were diagnosed with metachronous pancreatic cancers. PMID- 26805360 TI - [Safety and Feasibility of the Bioabsorbable Staple Line Reinforcement in Distal Pancreatic Resections]. AB - PURPOSE: The aim of this study was to evaluate the safety and feasibility of the bioabsorbable staple line reinforcement in distal pancreatic resection. PATIENTS & METHODS: Thirteen patients underwent distal pancreatic resection using the bioabsorbable staple line reinforcement between May 2014 and December 2014. Surgical complications were evaluated by Clavien-Dindo classification. RESULT: Median age was 64 years. Median operation time was 219 minutes and median blood loss was 490 mL. Complications>Grade 2 were observed in 3 patients. Among them, pancreatic fistula (Grade 2) was found in 2 patients and ileus (Grade 2) in 1. No surgical mortality was observed. DISCUSSION: Our results may suggest that the bioabsorbable staple line reinforcement is safe and feasible in distal pancreatic resection. PMID- 26805361 TI - [Analysis of Pancreaticoduodenectomy for Elderly Patients Aged 75 Years or Older]. AB - The feasibility of pancreaticoduodenectomy (PD) for elderly patients is controversial. Of 51 patients with pancreatic or bile duct tumor who underwent PD (except portal vein resection), the surgical results of 27 elderly patients aged 75 years or older (elderly group) we retrospectively evaluated and compared with those of 24 patients younger than 75 years (younger group). Although ASA-PS was significantly higher in the elderly group, we did not observe any significant difference in other background characteristics, complications, or length of hospital stay between the two groups. This study suggests that PD is probably safe and feasible with the appropriate surgical indication for elderly patients. PMID- 26805362 TI - [A Case of Invasive Ductal Carcinoma in the Fat Replacement of the Pancreatic Body and Tail]. AB - A 56 year-old woman with obesity (BMI3 2) and diabetes mellitus was diagnosed with right renal cell carcinoma. She underwent right nephrectomy 1 year ago. Seven months after surgery, CT revealed a rapidly growing mass near the spleen. The mass showed slight accumulation of FDG (SUVmax=2.4) on PET-CT. Since the lesion grew rapidly and was not enhanced in the early phase of enhanced CT, we diagnosed pancreatic cancer. Distal pancreatectomy and splenectomy were performed. The final pathological diagnosis was invasive ductal carcinoma in the fat replacement of the pancreatic body and tail. Postoperatively, the patient had no complications such as pancreatic fistula or aggravation of glucose intolerance. She received postoperative chemotherapy with gemcitabine. Since she developed pulmonary artery thrombosis, postoperative chemotherapy was interrupted after 8 courses. Thirty-two months after the surgery, she was still living without any recurrence. Acinar cells were absent in the fat replacement of the pancreas, but the pancreatic duct cells were still present. There was carcinoma in situ in the main pancreatic duct surrounding chronic inflammation. Fat replacement itself could be potentially precursor of the pancreatic cancer. PMID- 26805363 TI - [A Case of Brain Metastases from Pancreatic Cancer That Had Been Treated Effectively with FOLFIRINOX]. AB - We report a case of multiple brain metastases from pancreatic cancer, which had responded remarkably to FOLFIRINOX. A 47-year-old man had hypovascular tumors, 25 mm on the body and 23 mm on the uncus of the pancreas; multiple liver metastases; and skin metastasis. A diagnosis of unresectable pancreatic cancer, cT4N3M1 (HEP, LYM, PUL, SKI), cStage IVb was made. We chose FOLFIRINOX for treatment because of his young age and good performance status. After 6 courses, he showed decreasing tumor marker levels, an almost complete disappearance of the primary lesion, and reduced liver metastases. After 8 courses, abnormal behaviors were noted and we performed a head contrast-enhanced MRI, which revealed diffuse enhancement of the cerebral and cerebellar hemisphere. Multiple brain metastases from pancreatic cancer were diagnosed. We made the shift to palliative treatment, but his general condition was worsening and he died a month later, 7 months after the first diagnosis. PMID- 26805364 TI - [FOLFIRINOX Combination Chemotherapy in Patients with Metastatic or Recurrent Pancreatic Cancer--A Single Institution Experience]. AB - Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths in Japan. oxaliplatin: L-OHP, irinotecan: CPT-11, fluorouracil: 5-FU, and Leucovorin: l-LV (FOLFIRINOX) combination chemotherapy provided significant improvements in overall and progression-free survival in a phase III trial in France and in a phase II trial in Japan. As a result, this combination therapy was approved for use in Japan. We evaluated the efficacy of FOLFIRINOX in metastatic or recurrent pancreatic cancer. Between October 2014 and July 2015, 10 patients received mFOLFIRINOX as follows: 2-hour infusion of LOHP at 85 mg/m2, 2 hour infusion of l-LV at 200 mg/m2 and infusion of CPT-11 over 90 min at 150 mg/m2, followed by continuous infusion of 5-FU over 46 hours at 2,400mg/m2. Prior to the treatment, a 5-hydroxytryptamine receptor antagonist, aprepitant, and dexamethasone were given. The treatment was repeated every 2 weeks until disease progression, unacceptable toxicity, discontinuation as decided by the investigators, or patient refusal. The mean age of the patients was 65.0 years (range, 59-75 years), and 4 out of 10 patients were men. Only 2 patients had no prior therapy. Nine patients had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0. Eight patients had metastasis and 2 had locally recurrent disease. The median number of treatment cycles was 5 (range, 1-14). The relative dose intensities of 5-FU, L-OHP and CPT-11 were 93.3% (range, 58.3 100%), 84.0% (range, 63.2-100%), and 76.0% (range, 44.4-83.3%), respectively. The major Grade 3 and 4 hematological toxicities were neutropenia (40%), leucopenia (30%), and thrombocytopenia(10%). The major Grade 2 and 3 non-hematological toxicities were diarrhea (30%), nausea (60%), and vomiting (10%). Serious adverse events occurred in 2 patients. Severe biliary tract infection causing sepsis was observed in 1 patient with a biliary stent. Overwhelming post-splenectomy infection was observed in 1 patient after distal pancreatectomy. No cases of interstitial lung disease were observed. The 6-month progression-free and overall survival rates were 59.3% and 61.7%, respectively. The overall response rate was 10%, and the disease control rate was 90%(complete response [CR], n=0; partial response [PR], n=1; stable disease [SD], n=8; progressive disease [PD], n=1). Although FOLFIRINOX is associated with increased treatment efficacy and survival outcomes, because of its severe toxicity it cannot be administered to all patients. FOLFIRINOX can be used as the standard treatment for patients with a good performance status. PMID- 26805365 TI - [Treating Side Effects of FOLFIRINOX--A Study of the Effect of Hange-Shashin-To on Preventing Diarrhea]. AB - OBJECTIVES: FOLFIRINOX is an effective therapy for unresectable advanced pancreatic cancer. However, FOLFIRINOX has side effects of blood and gastrointestinal toxicity. Diarrhea, one of the side effects of CPT-11, sometimes becomes serious. We studied whether Hange-shashin-to could prevent diarrhea caused by CPT-11. METHODS: Seven patients who were diagnosed with unresectable pancreatic cancer, either Stage IVor recurrent disease, were enrolled. They took 2.5 g of Hange-shashin-to before each meal starting one day before FOLFIRINOX, and continued taking it for one week. We examined the occurrence of diarrhea by using CTCAE retrospectively. RESULTS: The median age was 61 years. The median number of chemotherapy courses was 4. The frequency of diarrhea was lower, compared to the results of ACCORD11 trial and the domestic phaseII clinical trials. In addition, Grade 3 or more serious diarrhea was not observed, even in the patients with genetic polymorphisms of UGT1A1. CONCLUSION: The incidence of diarrhea in patients treated with Hange-shashin-to in our department was lower compared to the ACCORD11 trial and domestic phase II clinical trials. Hange shashin-to is useful to allay the severity of diarrhea caused by CPT-11 in FOLFIRINOX therapy. PMID- 26805366 TI - [Nab-Paclitaxel plus Gemcitabine for Metastatic Pancreatic Cancer]. AB - Pancreatic ductal carcinoma is a highly aggressive cancer, with one of the highest mortality rates among gastrointestinal cancers. Nab-paclitaxel plus gemcitabine (GEM) significantly improved overall survival, progression-free survival, and response rate in a phase III trial in 151 community and academic centers in 11 countries. As a result, nab-paclitaxel plus GEM was approved for use in December 2014 in Japan. We report a case of a patient with pancreatic cancer who underwent this chemotherapy. A 47-year-old man was admitted to our hospital for evaluation of pancreatic lesions. Computed tomography revealed a hypoattenuating tumor in the body of the pancreas. After the patient underwent preoperative chemoradiotherapy under the diagnosis of cStage IVa cancer, we planned to perform distal pancreatectomy. However, this case was inoperable because we found 3 liver metastases during surgery. On postoperative day 14, we treated the patient with nab-paclitaxel plus GEM. Grade 2 toxicities included neutropenia, diarrhea, and peripheral neuropathy, but serious adverse events did not occur. The progression-free survival was 5 months. He remained alive for 7 months after the chemotherapy. In patients with metastatic pancreatic adenocarcinoma, nab-paclitaxel plus GEM can be considered as the standard treatment. PMID- 26805367 TI - [A Case of Pancreatic Head Cancer Treated with Pancreaticoduodenectomy Combined with Hepatic Artery Resection Following Neoadjuvant Chemotherapy]. AB - A 70-year-old woman was diagnosed with pancreatic head cancer with hepatic artery invasion by multi-detector computed tomography (MD-CT). After 3 courses of gemcitabine plus S-1 neoadjuvant therapy, the tumor size was not diminished; however, the tumor marker CA19-9 level was decreased to less than 90% of its initial level. Pancreaticoduodenectomy combined with hepatic artery resection was performed, and an end-to-end anastomosis was made between the common and proper hepatic artery to reconstruct the hepatic artery. The pathological examination indicated adenosquamous carcinoma, no vascular invasion, and negative margin status, and the efficacy of chemotherapy was classified as GradeIIb using Evans' classification. Usually, pancreatic head cancer with hepatic artery invasion is considered unresectable due to its high morbidity/mortality and poor prognosis. However, with the recently developed surgical strategy and appropriate therapeutic interventions, such as a combination of neoadjuvant chemotherapy and resection/reconstruction of the hepatic artery, a curative operation can be feasible for locally advanced pancreatic head cancer. PMID- 26805368 TI - [Adjuvant Surgery for Initially Unresectable Locally Advanced Pancreatic Cancer following Gemcitabine and S-1 Chemotherapy--A Case Report]. AB - A man in his 60s was admitted with obstructive jaundice. A hypovascular tumor, 55 mm in diameter, was detected in the pancreas head on imaging. The superior mesenteric vein showed severe stenosis bilaterally and the roots of all branches were invaded by the tumor. The tumor was diagnosed as unresectable pancreatic cancer, and chemotherapy of gemcitabine and S-1 was administered, resulting in a remarkable reduction of the tumor size. Following 7 courses of chemotherapy, a subtotal stomach-preserving pancreatoduodenectomy was carried out. Microscopic examination revealed no residual cancer cells in the resected specimen, indicating that pathological complete remission was obtained. Although some reports suggest that surgical treatment for patients with initially unresectable pancreas cancer who show excellent response to chemotherapy may improve the prognosis, further studies are needed. PMID- 26805369 TI - [A Case of Pancreatic Head Cancer Showing Pathological Complete Response to Neoadjuvant Chemoradiation Therapy]. AB - The patient was a 64-year-old woman. She was referred to our institute because of a chief complaint of upper abdominal pain. Abdominal computed tomographic scan revealed a 35 mm hypovascular tumor in the pancreatic head and superior mesenteric vein (SMV), as well as thrombosis. We chose neoadjuvant chemoradiation therapy (NACRT) (S-1/RT, 50.4 Gy/28 Fr) and anticoagulants. After the treatment, the primary lesion showed a partial response, and the SMV thrombosis was reduced. We performed pancreaticoduodenectomy. Histopathological examination revealed no cancer cells in the pancreas. Pathological evaluation revealed grade IV tumor according to the Evans classification. The patient had had no recurrence for 10 months after the pancreaticoduodenectomy. PMID- 26805370 TI - [The Clinical Efficacy of Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Carcinoma--Report of Two Cases Treated by Curative Pancreatectomy with Portal Vein Resection after Neoadjuvant Chemotherapy]. AB - We report 2 cases of curative resection of pancreatic cancer after neoadjuvant chemotherapy. A 60-year-old woman was diagnosed as having borderline resectable pancreatic ductal adenocarcinoma with invasion of the nerve plexus covering the superior mesenteric artery. The preoperative chemotherapy, 4 courses of gemcitabine and S-1, reduced the volume of tumor; pancreaticoduodenectomy with portal vein resection after chemotherapy resulted in R0 resection. Pathological examination of the resected specimen showed fibroid tissue with myxoid degeneration and mucinous lake surrounded by differentiated adenocarcinoma. A 40 year-old woman was diagnosed as having borderline resectable pancreatic ductal adenocarcinoma with invasion of the common hepatic artery and splenic artery. The preoperative chemotherapy, 4 courses of gemcitabine and S-1, reduced the tumor volume; distal pancreatectomy with portal vein resection after chemotherapy obtained R0 resection. Pathological examination of the resected specimen revealed that the majority of the tumor was fibrotic and necrotic tissue, and few cancer cells remained viable. Neoadjuvant chemotherapy has a potential to increase the rate of R0 resection. Furthermore, preoperative chemotherapy can help avoid unnecessary surgery by allowing time for potential metastasis to become obvious. PMID- 26805371 TI - [A Case of R0 Resection of Locally Advanced Pancreatic Cancer Following Chemoradiation Therapy]. AB - Patients with borderline resectable pancreatic cancer have a poorer prognosis than patients with resectable pancreatic cancer, but some cases treated with neoadjuvant chemoradiation therapy and radical surgery (R0 surgery) show long term survival. A 72-year-old woman presented with a history of back pain and weight loss. Computed tomography revealed a cancer of the pancreatic body encasing the celiac trunk, common hepatic artery, and portal vein. After neoadjuvant chemotherapy ( S-1) and carbon-ion radiotherapy, the tumor was considered to be resectable. Distal pancreatectomy with en bloc celiac trunk resection (DP-CAR), portal vein resection, and reconstruction was performed. The histopathologic findings showed that the effect of NACRT was gradeIIa (Evens' classification), and the surgical margins were histologically clear. S-1 was administered again for half a year as postoperative chemotherapy. With post operative follow-up of 1 year and 1 month after surgery, the patient shows no signs of recurrent disease. PMID- 26805372 TI - [A Case of Radical Resection for Locally Advanced Pancreatic Cancer with Positive Peritoneal Cytology Treated with Chemoradiotherapy]. AB - A 54-year-old female patient was admitted with obstructive jaundice. The patient was diagnosed with locally advanced unresectable pancreatic cancer of the head with invasion to the super mesenteric artery and the third portion of the duodenum. A biliary- and gastric-enteric bypass surgery was performed, and peritoneal lavage cytology was positive during surgery. After 6 courses of gemcitabine and S-1 combination chemotherapy, the CA19-9 level was normalized and the primary tumor shrank to 79% of its original size. Diagnostic laparoscopy revealed that distant metastasis was not detected and the peritoneal lavage cytology was negative. After additional chemoradiation therapy, a pancreaticoduodenectomy was perfomed. Microscopic investigation revealed that about 60% of the cancer tissue had been replaced by fibrosis and no cancer cells were found at the surgical margin. The patient was alive with no evidence of recurrence 17 months after radical surgery. PMID- 26805373 TI - [Two Cases of Liver Metastasis from Pancreatic Cancer with a Complete Response Owing to Chemotherapy]. AB - Case 1: The patient was a 42-year-old man who was diagnosed with intraductal papillary-mucinous carcinoma with liver metastasis. After S-1+gemcitabine and S-1 chemotherapy, the liver metastasis had disappeared and we performed a pancreaticoduodenectomy( PD). Case 2: The patient was a 70-year-old woman who was diagnosed with pancreatic cancer with liver metastasis. After gemcitabine chemotherapy, the liver metastasis had disappeared and we performed a PD. The prognosis of pancreatic cancer is dismal compared to other types of cancer, and for a Stage IVb cancers, the 5-year survival rate is reported to be approximately 3%. We report 2 cases of liver metastases from pancreatic cancer that disappeared in response to chemotherapy. Both patients underwent primary tumor resection after chemotherapy and experienced long-term survival. PMID- 26805374 TI - [A Case of Invasive Intraductal Papillary Mucinous Carcinoma, Penetrating the Stomach, Colon, and Jejunum]. AB - A 69-year-old woman was admitted to a nearby clinic complaining of abdominal pain. Abdominal CT showed a 10 cm diameter huge cystic lesion in the body and tail of the pancreas. The patient was referred to our institution for treatment. Endoscopic ultrasonography (EUS) revealed a cystic mass with a solid lesion. Endoscopic retrograde pancreatography(ERP) demonstrated mucous at the opening of the papilla of Vater and dilatation of the pancreatic duct with a solid nodule. Contrast radiography revealed a fistula from the tumor to the jejunum. A biopsy specimen from the lesion showed adenocarcinoma. Intraoperative findings showed a tumor occupying the pancreas body and tail with suspected invasion to the stomach, jejunum, and transverse colon. We performed distal pancreatectomy with partial resection of stomach, jejunum, and colon. Pathological findings showed an invasive type of IPMC, with invasion to the subserosal layer of the stomach and colon and the mucous layer of the jejunum. While IPMC is recognized as a slow growing malignancy, some cases of invasive carcinoma with fistulation into adjacent organs have been reported. To our knowledge, a case of IPMC penetrating to 3 adjacent organs is rare. PMID- 26805375 TI - [Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas Showing High Accumulation of 18F-Fluorodeoxyglucose (FDG)--A Case Report]. AB - The diagnosis of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas includes radiographic (CT, MRI) and endoscopic evaluation (ERCP, EUS). The treatment strategy is outlined in the 2012 International Consensus Guidelines (ICG). Herein, we report a case initially not indicated for surgery. Four months after the initial diagnosis, the cystic lesion transformed into a solid mass-like lesion visible on CT. FDG-PET showed abnormal FDG uptake at the same location. Surgical resection was performed immediately, and the tumor was diagnosed as IPMN with inflammation. FDG-PET showed a false-positive diagnosis for the malignancy in this case of IPMN. PMID- 26805376 TI - [Two Cases of Pancreatic Neuroendocrine Tumor with Liver Metastases Successfully Treated with Multidisciplinary Therapy including Multiple Surgical Resections]. AB - We report 2 cases of pancreatic neuroendocrine tumor with liver metastases successfully treated with multidisciplinary therapy, including multiple surgical resections. Case 1: A 63-year-old man underwent distal pancreatectomy and portal vein resection for a pancreatic body tumor. Histological analysis revealed the tumor was a pancreatic neuroendocrine tumor (p-NET), classified as NET G2. His metachronous liver metastases were treated with lateral sectionectomy and 2 rounds of transcatheter arterial chemoembolization (TACE). He is being treated with everolimus for para-aortic lymph node metastases and is alive 90 months after the primary operation. Case 2: A 64-year-old man underwent distal gastrectomy for a duodenal ulcer and distal pancreatectomy for a pancreatic tumor. The histological diagnosis was gastrinoma classified as NET G2. Hepatectomy (segmentectomy of segment 8 and partial hepatectomy) was performed twice for metachronous liver metastases. Everolimus has been administered for liver and para-aortic lymph node metastases, and the patient is alive 108 months after the primary operation. CONCLUSION: Multidisciplinary treatment should be considered for patients with p-NETs with multiple metastases. PMID- 26805377 TI - [A Resected Case of Acinar Cell Carcinoma Diagnosed by Endoscopic Ultrasound Guided Fine-Needle Aspiration Prior to Surgical Treatment]. AB - Acinar cell carcinoma (ACC) of the pancreas is an extremely rare tumor type, accounting for approximately 1% of all pancreatic neoplasm. Here, we report a rare case of ACC of the pancreas diagnosed on the basis of endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) findings prior to surgical treatment. A 73-years-old woman was being followed-up for chronic hepatitis C at our institution. Abdominal enhanced computed tomography showed an enhanced region, 16 mm in size, near the head of the pancreas on early-phase images. Magnetic resonance cholangiopancreatography did not show interruption or dilatation of the main pancreatic duct. Fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography showed an increased FDG uptake in the mass (SUVmax=12.7). EUS-FNA indicated a diagnosis of ACC, and pancreaticoduodenectomy was performed. Pathological examination confirmed the diagnosis of ACC. The patient was discharged after an 18-day hospital stay. Two years later, the patient has not shown any sings of recurrence. PMID- 26805378 TI - [Surgical Resection of Metachronous Hepatic Metastasis from Pancreatic Acinar Cell Carcinoma after Total Pancreatectomy]. AB - Pancreatic acinar cell carcinoma is rare. There is no consensus on a treatment strategy for metastatic lesions to the liver. We report of a 68-year-old man who received total pancreatectomy for pancreatic acinar cell carcinoma. One year after surgery, abdominal enhanced CT showed a small liver tumor in segment 8. We diagnosed this tumor as hepatic metastasis of pancreatic acinar cell carcinoma, and we resected it via partial liver resection. Pathological studies indicated a metastasis from pancreatic acinar cell carcinoma. The patient has been alive without recurrence for 7 months after the hepatectomy. There is no consensus on surgery for hepatic metastasis of acinar cell carcinoma, but if surgical resection is possible and safe, we consider it an appropriate treatment option. PMID- 26805382 TI - Kinetic stability of cystathionine beta-synthase can be modulated by structural analogs of S-adenosylmethionine: Potential approach to pharmacological chaperone therapy for homocystinuria. AB - Many pathogenic missense mutations in human cystathionine beta-synthase (CBS) cause misfolding of the mutant enzyme resulting in aggregation or rapid degradation of the protein. Subsequent loss of CBS function leads to CBS deficient homocystinuria (CBSDH). CBS contains two sets of binding sites for S adenosylmethionine (SAM) that independently regulate the enzyme activity and kinetically stabilize its regulatory domain. In the present study, we examined the hypothesis that CBS activation may be decoupled from kinetic stabilization and thus CBS regulatory domain can serve as a novel drug target for CBSDH. We determined the effect of SAM and its close structural analogs on CBS activity, their binding to and stabilization of the regulatory domain in the absence and presence of competing SAM. Binding of S-adenosylhomocysteine and sinefungin lead to stabilization of the regulatory domains without activation of CBS. Direct titrations and competition experiments support specific binding of these two SAM analogs to the stabilizing sites. Binding of these two ligands also affects the enzyme proteolysis rate supporting the role of the stabilizing sites in CBS dynamics. Our results indicate that binding of SAM to regulatory and stabilizing sites in CBS may have evolved to display an exquisite thermodynamic and structural specificity towards SAM as well as the ability to transduce the allosteric signal responsible for CBS activation. Thus, ligands may be developed to function as kinetic stabilizers or pharmacological chaperones without interfering with the physiological activation of CBS by SAM. PMID- 26805383 TI - Positive regulation of myoblast differentiation by medaka Neu3b sialidase through gangliosides desialylation. AB - Sialidase Neu3b is an unique enzyme conserved in medaka and tilapia, but not in mammals. Previous study revealed that medaka Neu3b is localized at cytosol and is a ganglioside-specific sialidase. Neu3b functions, however, have not been understood, while Neu3a sialidase, which is widely conserved from human to fish, is known as a regulator of neurite formation. Here, we investigated the biological function of Neu3b for C2C12 myoblast cell differentiation. Bioinformatics analysis using genome browser revealed the presence of neu3b gene in some orders of fish species such as Beloniformes, Perciformes and Cyprinodontiformes. With the treatment of 2% horse serum, Neu3b-overexpression accelerated myoblast cell differentiation to myotubes accompanied with up regulation of myogenesis biomarkers mRNA, myod and myog. Neu3b altered ganglioside composition in C2C12 cells results showing a decrease in GM2, and the increase of Lac-Cer, while desialylation of glycoproteins were not detected. Contrary to cell differentiation, Neu3b cell proliferation was suppressed in normal growth medium. To understand the mechanism of the alteration of cell differentiation and proliferation, phosphorylation of signal molecules in EGFR/ERK pathway was investigated. Neu3b induced a decline in phosphorylation of ERK and EGFR. Surprisingly, immuno-blot and real-time PCR analysis revealed that down-regulation of egfr gene could be involved in the acceleration of cell differentiation by Neu3b. These results suggested that Neu3b sialidase is a positive regulator for myoblast differentiation, similar with mammalian cytosolic sialidase Neu2. PMID- 26805384 TI - Investigating the structural impact of S311C mutation in DRD2 receptor by molecular dynamics & docking studies. AB - Dopamine receptors (DR) are neuronal cell surface proteins that mediate the action of neurotransmitter dopamine in brain. Dopamine receptor D2 (DRD2) that belongs to G-protein coupled receptors (GPCR) family is a major therapeutic target for of various neurological and psychiatric disorders in human. The third inter cellular loop (ICL3) in DRD2 is essential for coupling G proteins and several signaling scaffold proteins. A mutation in ICL3 can interfere with this binding interface, thereby altering the DRD2 signaling. In this study we have examined the deleterious effect of serine to cysteine mutation at position 311 (S311C) in the ICL3 region that is implicated in diseases like schizophrenia and alcoholism. An in silico structure modeling approach was employed to determine the wild type (WT) and mutant S311C structures of DRD2, scaffold proteins - Galphai/o and NEB2. Protein-ligand docking protocol was exercised to predict the interactions of natural agonist dopamine with both the WT and mutant structures of DRD2. Besides, atomistic molecular dynamics (MD) simulations were performed to provide insights into essential dynamics of the systems-unbound and dopamine bound DRD2 (WT and mutant) and three independent simulations for Galphai, Galphao and NEB2 systems. To provide information on intra-molecular arrangement of the structures, a comprehensive residue interactions network of both dopamine bound WT and mutant DRD2 protein were studied. We also employed a protein-protein docking strategy to find the interactions of scaffold proteins - Galphai/o and NEB2 with both dopamine bound WT and mutant structures of DRD2. We observed a marginal effect of the mutation in dopamine binding mechanism on the trajectories analyzed. However, we noticed a significant structural alteration of the mutant receptor which affects Galphai/o and NEB2 binding that can be causal for malfunctioning in cAMP-dependent signaling and Ca(+) homeostasis in the brain dopaminergic system leading to neuropsychiatric disorders. PMID- 26805380 TI - Targeting mTOR for the treatment of B cell malignancies. AB - Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions as a key regulator of cell growth, division and survival. Many haematologic malignancies exhibit elevated or aberrant mTOR activation, supporting the launch of numerous clinical trials aimed at evaluating the potential of single agent mTOR-targeted therapies. While promising early clinical data using allosteric mTOR inhibitors (rapamycin and its derivatives, rapalogs) have suggested activity in a subset of haematologic malignancies, these agents have shown limited efficacy in most contexts. Whether the efficacy of these partial mTOR inhibitors might be enhanced by more complete target inhibition is being actively addressed with second generation ATP-competitive mTOR kinase inhibitors (TOR-KIs), which have only recently entered clinical trials. However, emerging preclinical data suggest that despite their biochemical advantage over rapalogs, TOR-KIs may retain a primarily cytostatic response. Rather, combinations of mTOR inhibition with other targeted therapies have demonstrated promising efficacy in several preclinical models. This review investigates the current status of rapalogs and TOR-KIs in B cell malignancies, with an emphasis on emerging preclinical evidence of synergistic combinations involving mTOR inhibition. PMID- 26805386 TI - Thymosin beta4 promotes oligodendrogenesis in the demyelinating central nervous system. AB - Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). No effective remyelination therapies are in use. We hypothesized that thymosin beta4 (Tbeta4) is an effective remyelination treatment by promoting differentiation of oligodendrocyte progenitor cells (OPCs), and that the epidermal growth factor receptor (EGFR) signaling pathway contributes to this process. Two demyelination animal models were employed in this study: 1) experimental autoimmune encephalomyelitis (EAE), an animal model of MS. EAE mice were treated daily for 30days, with Tbeta4 or saline treatment initiated on the day of EAE onset; and 2) cuprizone diet model, a non-inflammatory demyelination model. The mice were treated daily for 4weeks with Tbeta4 or saline after fed a cuprizone diet for 5weeks. Immunofluorescent staining and Western blot were performed to measure the differentiation of OPCs, myelin and axons, respectively. To obtain insight into mechanisms of action, the expression and activation of the EGFR pathway was measured. AG1478, an EGFR inhibitor, was employed in a loss-of function study. Data revealed that animals in both demyelination models exhibited significant reduction of myelin basic protein (MBP(+)) levels and CNPase(+) oligodendrocytes. Treatment of EAE mice with Tbeta4 significantly improved neurological outcome. Double immunofluorescent staining showed that Tbeta4 significantly increased the number of newly generated oligodendrocytes identified by BrdU(+)/CNPase(+) cells and MBP(+) mature oligodendrocytes, and reduced axonal damage in the EAE mice compared with the saline treatment. The newly generated mature oligodendrocytes remyelinated axons, and the increased mature oligodendrocytes significantly correlated with functional improvement (r=0.73, p<0.05). Western blot analysis revealed that Tbeta4 treatment increased expression and activation of the EGFR pathway. In the cuprizone demyelination model, Tbeta4 treatment was confirmed that significantly increased OPC differentiation and remyelination, and increased the expression of EGFR and activated the EGFR pathway in the demyelinating corpus callosum. In cultured OPCs, blockage of the activation of the EGFR pathway with AG1478 abolished the Tbeta4-increased OPC differentiation. Collectively, these findings indicate that: 1) Tbeta4 increases proliferation of OPCs and the maturation of OPCs to myelinating oligodendrocytes which in concert, likely contribute to the beneficial effect of Tbeta4 on EAE, 2) EGFR upregulated and activated by Tbeta4 may mediate the process of OPC differentiation, and 3) Tbeta4 could potentially be developed as a therapy for MS patients, and for other demyelinating neurological disorders. PMID- 26805388 TI - Technology and ENT. PMID- 26805387 TI - Interplay between TDP-43 and docosahexaenoic acid-related processes in amyotrophic lateral sclerosis. AB - BACKGROUND: Docosahexaenoic acid (DHA), a key lipid in nervous system homeostasis, is depleted in the spinal cord of sporadic amyotrophic lateral sclerosis (sALS) patients. However, the basis for such loss was unknown. METHODS: DHA synthetic machinery was evaluated in spinal cord samples from ALS patients and controls by immunohistochemistry and western blot. Further, lipid composition was measured in organotypic spinal cord cultures by gas chromatography and liquid chromatography coupled to mass spectrometry. In these samples, mitochondrial respiratory functions were measured by high resolution respirometry. Finally, Neuro2-A and stem cell-derived human neurons were used for evaluating mechanistic relationships between TDP-43 aggregation, oxidative stress and cellular changes in DHA-related proteins. RESULTS: ALS is associated to changes in the spinal cord distribution of DHA synthesis enzymatic machinery comparing ten ALS cases and eight controls. We found increased levels of desaturases (ca 95% increase, p<0.001), but decreased amounts of DHA-related beta-oxidation enzymes in ALS samples (40% decrease, p<0.05). Further, drebrin, a DHA-dependent synaptic protein, is depleted in spinal cord samples from ALS patients (around 40% loss, p<0.05). In contrast, chronic excitotoxicity in spinal cord increases DHA acid amount, with both enhanced concentrations of neuroprotective docosahexaenoic acid derived resolvin D, and higher lipid peroxidation-derived molecules such as 8-iso prostaglandin-F2-alpha (8-iso-PGF2alpha) levels. Since alpha-tocopherol improved mitochondrial respiratory function and motor neuron survival in these conditions, it is suggested that oxidative stress could boost motor neuron loss. Cell culture and metabolic flux experiments, showing enhanced expression of desaturases (FADS2) and beta-oxidation enzymes after H2O2 challenge suggest that DHA production can be an initial response to oxidative stress, driven by TDP-43 aggregation and drebrin loss. Interestingly, these changes were dependent on cell type used, since human neurons exhibited losses of FADS2 and drebrin after oxidative stress. These features (drebrin loss and FADS2 alterations) were also produced by transfection by aggregation prone C-terminal fragments of TDP-43. CONCLUSIONS: sALS is associated with tissue-specific DHA-dependent synthetic machinery alteration. Furthermore, excitotoxicity sinergizes with oxidative stress to increase DHA levels, which could act as a response over stress, involving the expression of DHA synthetic enzymes. Later on, this allostatic overload could exacerbate cell stress by contributing to TDP-43 aggregation. This, at its turn, could blunt this protective response, overall leading to DHA depletion and neuronal dysfunction. PMID- 26805389 TI - Glue ear: how good is the information on the World Wide Web? AB - OBJECTIVE: This paper objectively evaluates current information available to the general public related to glue ear on the World Wide Web. METHODS: The term 'glue ear' was typed into the 3 most frequently used internet search engines - Google, Bing and Yahoo - and the first 20 links were analysed. The first 400 words of each page were used to calculate the Flesch-Kincaid readability score. Each website was subsequently graded using the Discern instrument, which gauges quality and content of literature. RESULTS: The websites Webmd.boots.com, Bupa.co.uk and Patient.co.uk received the highest overall scores. These reflected top scores in either readability or Discern instrument assessment, but not both. Readability and Discern scores increased with the presence of a marketing or advertising incentive. The Patient.co.uk website had the highest Discern score and third highest readability score. CONCLUSION: There is huge variation in the quality of information available to patients on the internet. Some websites may be accessible to a wide range of reading ages but have poor quality content, and vice versa. Clinicians should be aware of indicators of quality, and use validated instruments to assess and recommend literature. PMID- 26805390 TI - Digoxin in patients with atrial fibrillation and heart failure: A risk factor or a marker of increased mortality? PMID- 26805391 TI - Non-sustained ventricular tachycardia in patients with congenital heart disease: An important sign? AB - BACKGROUND: Sustained ventricular tachycardia (susVT) and ventricular fibrillation (VF) are observed in adult patients with congenital heart disease (CHD). These dysrhythmias may be preceded by non-sustained ventricular tachycardia (NSVT). The aims of this study are to examine the 1] time course of ventricular tachyarrhythmia (VTA) in a large cohort of patients with various CHDs and 2] the development of susVT/VF after NSVT. METHODS: In this retrospective study, patients with VTA on ECG, 24-hour Holter or ICD-printout or an out-of hospital-cardiac arrest due to VF were included. In patients with an ICD, the number of shocks was studied. RESULTS: Patients (N=145 patients, 59% male) initially presented with NSVT (N=103), susVT (N=25) or VF (N=17) at a mean age of 40 +/- 14 years. Prior to VTA, 58 patients had intraventricular conduction delay, 14 an impaired ventricular dysfunction and 3 had coronary artery disease. susVT/VF rarely occurred in patients with NSVT (N=5). Fifty-two (36%) patients received an ICD; appropriate and inappropriate shocks, mainly due to supraventricular tachycardia (SVT), occurred in respectively 15 (29%) (NSVT: N=1, susVT: N=9, VF: N=5) and 12 (23%) (NSVT: N=4, susVT: N=5, VF: N=3) patients. CONCLUSIONS: VTA in patients with CHD appear on average at the age of 40 years. susVT/VF rarely developed in patients with only NSVT, whereas recurrent episodes of susVT/VF frequently developed in patients initially presenting with susVT/VF. Hence, a wait-and-see treatment strategy in patients with NSVT and aggressive therapy of both episodes of VTA and SVT in patients with susVT/VF seems justified. PMID- 26805392 TI - Antioxidant Activity/Capacity Measurement. 2. Hydrogen Atom Transfer (HAT)-Based, Mixed-Mode (Electron Transfer (ET)/HAT), and Lipid Peroxidation Assays. AB - Measuring the antioxidant activity/capacity levels of food extracts and biological fluids is useful for determining the nutritional value of foodstuffs and for the diagnosis, treatment, and follow-up of numerous oxidative stress related diseases. Biologically, antioxidants play their health-beneficial roles via transferring a hydrogen (H) atom or an electron (e(-)) to reactive species, thereby deactivating them. Antioxidant activity assays imitate this action; that is, antioxidants are measured by their H atom transfer (HAT) or e(-) transfer (ET) to probe molecules. Antioxidant activity/capacity can be monitored by a wide variety of assays with different mechanisms, including HAT, ET, and mixed-mode (ET/HAT) assays, generally without distinct boundaries between them. Understanding the principal mechanisms, advantages, and disadvantages of the measurement assays is important for proper selection of method for valid evaluation of antioxidant properties in desired applications. This work provides a general and up-to-date overview of HAT-based, mixed-mode (ET/HAT), and lipid peroxidation assays available for measuring antioxidant activity/capacity and the chemistry behind them, including a critical evaluation of their advantages and drawbacks. PMID- 26805395 TI - Biomechanical evaluation of a non-locking pre-manufactured loop suture technique compared to a three-loop pulley suture in a canine calcaneus tendon avulsion model. AB - OBJECTIVE: The purpose of this cadaveric study was to compare the strength of a non-locking pre-manufactured loop (SpeedWhipTM [SW]) suture pattern using Fiberwire(r) with the three-loop pulley (TLP) suture pattern using polypropylene for the surgical repair of canine calcaneal tendon avulsion injuries. METHODS: In vitro biomechanical study using 22 paired tendons collected from 11 canine cadavers. Paired tendons were repaired with either a SW suture pattern using Fiberloop(r) suture or a TLP suture pattern using polypropylene suture. Tensile loads required to create a 1 mm gap, 3 mm gap, and construct failure were measured. RESULTS: The mean loads to achieve a 1 mm gap in the TLP and SW constructs were not significantly different. Gap formation at 3 mm occurred at significantly lower loads for the SW (106.4 +/- 21.5N) than for the TLP (127.2 +/ 27.5N) (p = 0.05). The mean loads to construct failure for the TLP (172.8 +/- 39.4N) and SW (131.3 +/- 34.3N) were significantly different (p = 0.001). CLINICAL SIGNIFICANCE: The TLP with polypropylene suture is superior to the SW using Fiberloop(r) at resistance to 3 mm gap formation. PMID- 26805394 TI - Blocking protein phosphatase 2A signaling prevents endothelial-to-mesenchymal transition and renal fibrosis: a peptide-based drug therapy. AB - Endothelial-to-mesenchymal transition (EndMT) contributes to the emergence of fibroblasts and plays a significant role in renal interstitial fibrosis. Protein phosphatase 2A (PP2A) is a major serine/threonine protein phosphatase in eukaryotic cells and regulates many signaling pathways. However, the significance of PP2A in EndMT is poorly understood. In present study, the role of PP2A in EndMT was evaluated. We demonstrated that PP2A activated in endothelial cells (EC) during their EndMT phenotype acquisition and in the mouse model of obstructive nephropathy (i.e., UUO). Inhibition of PP2A activity by its specific inhibitor prevented EC undergoing EndMT. Importantly, PP2A activation was dependent on tyrosine nitration at 127 in the catalytic subunit of PP2A (PP2Ac). Our renal-protective strategy was to block tyrosine127 nitration to inhibit PP2A activation by using a mimic peptide derived from PP2Ac conjugating a cell penetrating peptide (CPP: TAT), termed TAT-Y127WT. Pretreatment with TAT-Y127WT was able to prevent TGF-beta1-induced EndMT. Administration of the peptide to UUO mice significantly ameliorated renal EndMT level, with preserved density of peritubular capillaries and reduction in extracellular matrix deposition. Taken together, these results suggest that inhibiting PP2Ac nitration using a mimic peptide is a potential preventive strategy for EndMT in renal fibrosis. PMID- 26805396 TI - Structure-Guided Discovery of Antitubercular Agents That Target the Gyrase ATPase Domain. AB - In this study we explored the pharmaceutically underexploited ATPase domain of DNA gyrase (GyrB) as a potential platform for developing novel agents that target Mycobacterium tuberculosis. In this effort a combination of ligand- and structure based pharmacophore modeling was used to identify structurally diverse small molecule inhibitors of the mycobacterial GyrB domain based on the crystal structure of the enzyme with a pyrrolamide inhibitor (PDB ID: 4BAE). Pharmacophore modeling and subsequent in vitro screening resulted in an initial hit compound 5 [(E)-5-(5-(2-(1H-benzo[d]imidazol-2-yl)-2-cyanovinyl)furan-2 yl)isophthalic acid; IC50 =4.6+/-0.1 MUm], which was subsequently tailored through a combination of molecular modeling and synthetic chemistry to yield the optimized lead compound 24 [(E)-3-(5-(2-cyano-2-(5-methyl-1H-benzo[d]imidazol-2 yl)vinyl)thiophen-2-yl)benzoic acid; IC50 =0.3+/-0.2 MUm], which was found to display considerable in vitro efficacy against the purified GyrB enzyme and potency against the H37 Rv strain of M. tuberculosis. Structural handles were also identified that will provide a suitable foundation for further optimization of these potent analogues. PMID- 26805398 TI - Copolymerization of Ethylene and Polar Monomers by Using Ni/IzQO Catalysts. AB - The replacement of precious metals in catalysis by earth-abundant metals is currently one of the urgent challenges for chemists. Whereas palladium-catalyzed copolymerization of ethylene and polar monomers is a valuable method for the straightforward synthesis of functionalized polyolefins, the corresponding nickel based catalysts have suffered from poor thermal tolerance and low molecular weight of the polymers formed. Herein, we report a series of neutral nickel complexes bearing imidazo[1,5-a]quinolin-9-olate-1-ylidene (IzQO) ligands. The Ni/IzQO system can catalyze ethylene polymerization at 50-100 degrees C with reasonable activity in the absence of any cocatalyst, whereas most known nickel based catalysts are deactivated at this temperature range. The Ni/IzQO catalyst was successfully applied to the copolymerization of ethylene with allyl monomers to obtain the corresponding copolymers with the highest molecular weight reported for a Ni-catalyzed system. PMID- 26805397 TI - Interleukin-1B 31 C>T polymorphism combined with Helicobacter pylori-modified gastric cancer susceptibility: evidence from 37 studies. AB - Gastric cancer is one of the most common malignancies worldwide. Interleukin-1 beta (IL-1beta) is a pro-inflammatory cytokine and potent inhibitor of gastric acid secretion. Some studies provided evidence of the association between IL-1B 31 polymorphism and gastric cancer risk while other studies did not. Therefore, we conducted a comprehensive meta-analysis to reassess the association. A systematic literature search of the PubMed and EMBASE databases identified 37 studies with 6108 cases and 8980 controls for this meta-analysis. The crude odd ratios (ORs) and the 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Meta-regression was used to determine the major source of heterogeneity across the studies. The pooled analysis did not suggest the significant association of IL-1B 31 C>T polymorphism with gastric cancer risk. Stratified analysis was performed by ethnicity, source of control, genotype method, and indicated a significantly increased gastric cancer risk associated with IL-1B 31T variant in the population-based subgroup (heterozygous model: OR = 1.22, 95% CI = 1.03-1.45). Moreover, stratified analysis by Helicobacter pylori infection status indicated that IL-1B 31 polymorphism increased gastric cancer risk in infection-positive subgroup (homozygous model: OR = 1.35, 95% CI = 1.02 1.78; heterozygous model: OR = 1.31, 95% CI = 1.04-1.66; recessive model: OR = 1.29, 95% CI = 1.04-1.61). The study suggested that IL-1B 31 polymorphism might confer susceptibility to gastric cancer in the presence of H. pylori infection, indicating a gene-environment interaction in gastric carcinogenesis. PMID- 26805400 TI - [Continuum, the continuing education platform based on a competency matrix]. AB - Competency-Based Education is a learning method that has changed the traditional teaching-based focus to a learning-based one. Students are the centre of the process, in which they must learn to learn, solve problems, and adapt to changes in their environment. The goal is to provide learning based on knowledge, skills (know-how), attitude and behaviour. These sets of knowledge are called competencies. It is essential to have a reference of the required competencies in order to identify the need for them. Their acquisition is approached through teaching modules, in which one or more skills can be acquired. This teaching strategy has been adopted by Continuum, the distance learning platform of the Spanish Paediatric Association, which has developed a competency matrix based on the Global Paediatric Education Consortium training program. In this article, a review will be presented on the basics of Competency-Based Education and how it is applied in Continuum. PMID- 26805401 TI - Anisotropic lattice response induced by a linearly-polarized femtosecond optical pulse excitation in interfacial phase change memory material. AB - Optical excitation of matter with linearly-polarized femtosecond pulses creates a transient non-equilibrium lattice displacement along a certain direction. Here, the pump and probe pulse polarization dependence of the photo-induced ultrafast lattice dynamics in (GeTe)2/(Sb2Te3)4 interfacial phase change memory material is investigated under obliquely incident conditions. Drastic pump polarization dependence of the coherent phonon amplitude is observed when the probe polarization angle is parallel to the c-axis of the sample, while the pump polarization dependence is negligible when the probe polarization angle is perpendicular to the c-axis. The enhancement of phonon oscillation amplitude due to pump polarization rotation for a specific probe polarization angle is only found in the early time stage (<=2 ps). These results indicate that the origin of the pump and probe polarization dependence is dominantly attributable to the anisotropically-formed photo-excited carriers which cause the directional lattice dynamics. PMID- 26805404 TI - Effect of increased concentrate allotment before evening grazing on herbage intake, nitrogen utilization and rumen fermentation in dairy cows grazed on perennial ryegrass pasture. AB - Two experiments were conducted to elucidate the effect of increased concentrate allotment before evening grazing on herbage intake, nitrogen utilization and rumen fermentation in dairy cows. In experiment 1, nine lactating cows were grazed in the morning and evening sessions (2.5 h each). The cows were allocated to treatments of three concentrate allotment levels before the evening grazing session by altering proportions to daily total offered; 25%, 50% and 75%. Daily herbage dry matter intake quadratically decreased with increasing the concentrate allotment levels (P < 0.05). Nitrogen utilization was similar among treatments. To investigate diurnal changes in rumen fermentation, a second experiment was conducted where six ruminally cannulated non-lactating dairy cows grazed in the morning and evening sessions (3 h each) were subjected to the same treatments as experiment 1. Total volatile fatty acid concentration in the rumen linearly increased with increasing the concentrate allotment levels throughout the pre evening grazing session to the post-morning grazing session (P < 0.01). The results indicate that dairy cows reduce daily herbage intake but do not alter nitrogen utilization with increasing concentrate allotment before evening grazing. (c) 2016 Japanese Society of Animal Science. PMID- 26805402 TI - The acute and long-term L-DOPA effects are independent from changes in the activity of dorsal raphe serotonergic neurons in 6-OHDA lesioned rats. AB - BACKGROUND AND PURPOSE: L-DOPA is still the most efficacious pharmacological treatment for Parkinson's disease. However, in the majority of patients receiving long-term therapy with L-DOPA, its efficacy is compromised by motor complications, notably L-DOPA-induced dyskinesia. Evidence suggests that the serotonergic system is involved in the therapeutic and the side effects of L DOPA. Here, we investigate if long-term L-DOPA treatment alters the activity of the dorsal raphe nucleus (DRN) and its responses to serotonergic drugs. EXPERIMENTAL APPROACH: We measured the responses of serotonergic neurons to acute and chronic L-DOPA treatment using in vivo electrophysiological single unit extracellular recordings in the 6-OHDA-lesion rat model of Parkinson's disease. KEY RESULTS: The results showed that neither acute nor chronic L-DOPA administration (6 mg.kg(-1) s.c.) altered the properties of serotonergic-like neurons. Furthermore, no correlation was found between the activity of these neurons and the magnitude of L-DOPA-induced dyskinesia. In dyskinetic rats, the inhibitory response induced by the 5-HT1A receptor agonist 8-OH-DPAT (0.0625-16 MUg.kg(-1) , i.v.) was preserved. Nonetheless, L-DOPA impaired the ability of the serotonin reuptake inhibitor fluoxetine (0.125-8 mg.kg(-1) , i.v) to inhibit DRN neuron firing rate in dyskinetic animals. CONCLUSIONS AND IMPLICATIONS: Although serotonergic neurons are involved in the dopaminergic effects of L-DOPA, we provide evidence that the effect of L-DOPA is not related to changes of the activity of DRN neurons. Rather, L-DOPA might reduce the efficacy of drugs that normally enhance the extracellular levels of serotonin. LINKED ARTICLES: This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc. PMID- 26805406 TI - Inflammatory cytokines prime adipose tissue mesenchymal stem cells to enhance malignancy of MCF-7 breast cancer cells via transforming growth factor-beta1. AB - Mesenchymal stem cells from human adipose tissue (hASCs) are proposed as suitable tools for soft tissue engineering and reconstruction. Although it is known that hASCs have the ability to home to sites of inflammation and tumor niche, the role of inflammatory cytokines in the hASCs-affected tumor development is not understood. We found that interferon-gamma (IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha) prime hASCs to produce soluble factors which enhance MCF 7 cell line malignancy in vitro. IFN-gamma and/or TNF-alpha-primed hASCs produced conditioned media (CM) which induced epithelial to mesenchymal transition (EMT) of MCF-7 cells by reducing E-Cadherin and increasing Vimentin expression. Induced EMT was accompanied by increased invasion, migration, and urokinase type plasminogen activator (uPA) expression in MCF-7 cells. These effects were mediated by increased expression of transforming growth factor-beta1(TGF-beta1) in cytokines-primed hASCs, since inhibition of type I TGF-beta1 receptor on MCF-7 cells and neutralization of TGF-beta1 disabled the CM from primed hASCs to increase EMT, cell migration, and uPA expression in MCF-7 cells. Obtained data suggested that IFN-gamma and/or TNF-alpha primed hASCs might enhance the malignancy of MCF-7 cell line by inducing EMT, cell motility and uPA expression in these cells via TGF-beta1-Smad3 signalization, with potentially important implications in breast cancer progression. PMID- 26805407 TI - Outcome after prenatal diagnosis of congenital anomalies of the kidney and urinary tract. AB - Congenital anomalies of the kidney and urinary tract are common findings on fetal ultrasound. The aim of this prospective observational study was to describe outcome and risk factors in 115 patients born 1995-2001. All prenatally diagnosed children were stratified into low- and high-risk group and followed postnatally clinically and by imaging at defined endpoints. Risk factors were evaluated using odds ratios. Neonatal diagnosis included pelvi-ureteric junction obstruction (n = 33), vesicoureteral reflux (n = 27), solitary mild pelvic dilatation (postnatal anteroposterior diameter 5-10 mm; n = 25), and further diagnosis as primary obstructive megaureter, unilateral multicystic dysplastic kidney, renal dysplasia and posterior urethral valves. In 38 children with prenatal isolated hydronephrosis, ultrasound normalized at median age of 1.2 years (range 0.1-9). Surgery was performed in 34 children at median age of 0.4 years (0.1-10.8). Persistent renal anomalies without surgery were present in 43 children and followed in 36 for median time of 16 years (12.2-18). Oligohydramnios and postnatal bilateral anomalies were significantly associated with surgery and impaired renal function. CONCLUSION: The majority of children had a favourable postnatal outcome, in particular children with prenatally low risk, i.e. isolated uni- or bilateral hydronephrosis. Oligohydramnios and postnatal bilateral anomalies were risk factors for non-favourable outcome. WHAT IS KNOWN: * In congenital anomalies of the kidney and urinary tract significantly poorer outcome is known in patients with bilateral renal hypoplasia or solitary kidney associated with posterior urethral valves. * Other factors as proteinuria and vesicoureteral reflux were associated with a higher risk of progression to chronic renal failure in these patients. What is New: * Unlike other studies giving us above-mentioned information, we included all patients with any kind of prenatally diagnosed congenital anomalies of the kidney and urinary tract. Our study shows long-term follow up (median 16 years, range 12.2-18 years), especially in patients not needing surgery, but with persistent anomalies. * During postnatal long-term follow up (median 2.2 years, range 0.1-18 years) one third each showed normalization, need of surgery or persistence of anomalies without need of surgery. Our study revealed a good prognosis in the majority of these children, in particular with prenatally low risk, i.e. isolated uni- or bilateral hydronephrosis, and revealed oligohydramnios and postnatal bilateral anomalies as risk factors for a non-favourable outcome, defined as need of surgery, persistent anomalies with impaired renal function, end stage renal failure or death. PMID- 26805408 TI - Thyroid carcinoma in children, adolescents and adults, both spontaneous and after childhood radiation exposure. AB - Thyroid carcinoma is the most common second malignancy for childhood cancer survivors. Radiation exposure is linked to risk. Thyroid nodules in children have a high risk for malignancy, whether spontaneous or after radiation. Due to the extremely limited available paediatric data, we sought to review a series of patients with thyroid carcinoma, seen over 25 years. Forty-six patients were identified. Thirty-nine (84.8 %) had papillary thyroid carcinoma, five (10.9 %) follicular carcinoma and 2 (4.3 %) medullary thyroid carcinoma (MEN2B). Thirty three (71.7 %) had childhood radiation exposure (17 females) with thyroid malignancy occurring 6-37 years later. The smallest nodule size found on surveillance to have thyroid malignancy was 4 mm. Thyroid cancer in patients 16 years and under was seen in 22 patients (47.8 %). All had total thyroidectomy, with initial central node clearance from 2005. Diagnostic rTSH stimulated I(123) scan was followed by ablative I(131) if any uptake was seen. Sixteen (32.6 %) had metastases. Twenty-four (52.2 %) had I(131), four requiring multiple courses. Forty-two remain alive and well. CONCLUSION: Ultrasound screening is required for early diagnosis as small nodule size is not predictive of benign histology or absence of metastases. Central node clearance provides better outcome. Despite metastatic disease at presentation for some, prognosis is favourable. WHAT IS KNOWN: * Incidence of thyroid cancer has been increasing and radiation exposure in childhood cancer survivors is clearly linked to risk. * Published guidelines in many places can only provide very low level evidence due to extremely limited available paediatric data. What is New: * Paper provides good evidence to confirm existing views with the largest cohort of thyroid cancer reported to date in the paediatric age group in Australia, and the largest cohort in Australia where there have been specific high risks of radiation exposure. The only other reported larger studies have come from the Children's Oncology Group and Childhood Cancer Survivor Study [24]. * Using diagnostic rTSH stimulated I(123) scan 6 weeks after surgery helps to determine if radioactive iodine ablation is necessary and limits unnecessary bone marrow exposure for young patients in whom future leukaemia is of greater concern. PMID- 26805409 TI - Resilience in schizophrenia: A comparative study between a remote island and an urban area in Japan. AB - The resilience levels between patients with schizophrenia residing in a rural island and a metropolitan area in Tokyo, Japan, was compared and the factors associated with resilience were explored. The Resilience Scale (RS) and EuroQol were assessed, together with biological markers and multiple demographic variables. No significant difference was found in the RS scores between the two groups (40 subjects each). However, longer duration of illness and higher EuroQol score were significantly associated with a greater RS score, which indicates that potentially successful adaptation and subjective perspectives appear more pertinent than the degree of urbanicity in determining resilience levels. PMID- 26805410 TI - Abnormally increased and incoherent resting-state activity is shared between patients with schizophrenia and their unaffected siblings. AB - BACKGROUND: Several resting-state neuroimaging studies in schizophrenia indicate an excessive brain activity while others report an incoherent brain activity at rest. No direct evidence for the simultaneous presence of both excessive and incoherent brain activity has been established to date. Moreover, it is unclear whether unaffected siblings of schizophrenia patients who share half of the affected patient's genotype also exhibit the excessive and incoherent brain activity that may render them vulnerable to the development of schizophrenia. METHODS: 27 pairs of schizophrenia patients and their unaffected siblings, as well as 27 healthy controls, were scanned using gradient-echo echo-planar imaging at rest. By using amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (Reho), we investigated the intensity and synchronization of local spontaneous neuronal activity in three groups. RESULTS: We observed that increased amplitude and reduced synchronization (coherence) of spontaneous neuronal activity were shared by patients and their unaffected siblings. The key brain regions with this abnormal neural pattern in both patients and siblings included the middle temporal, orbito-frontal, inferior occipital and fronto insular gyrus. CONCLUSIONS: This abnormal neural pattern of excessive and incoherent neuronal activity shared by schizophrenia patients and their healthy siblings may improve our understanding of neuropathology and genetic predisposition in schizophrenia. PMID- 26805411 TI - Free thyroxine levels are associated with cognitive changes in individuals with a first episode of psychosis: A prospective 1-year follow-up study. AB - The results of previous cross-sectional studies suggest that free thyroxine (FT4) levels are associated with cognitive abilities (particularly attention/vigilance) during the early stages of psychosis. We aimed to explore whether hypothalamic pituitary-thyroid hormones predict cognitive changes in a 1-year longitudinal study following first episodes of psychosis (FEP). We studied 36 FEP patients and a control group of 50 healthy subjects (HS). Plasma levels of thyroid-stimulating hormone (TSH) and FT4 were measured. Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery (MCCB). FEP patients were assessed twice (baseline and after 1year), whereas HS were assessed only once. We compared cognitive changes at 1year between three groups based on baseline FT4 levels: 1) lowest quartile (Q1, FT4<1.16ng/dL); 2) medium quartiles (Q2-Q3, FT4 1.16 1.54ng/dL); and 3) highest quartile (Q4, FT4>1.54ng/dL). No differences in TSH or FT4 levels were found between HS and FEP patients. All participants had FT4 levels within the normal range. HS outperformed FEP patients in all cognitive tasks. In relation to the relationship between FT4 levels and cognitive changes, a U-shaped pattern was observed: FEP patients from the middle quartiles (Q2-Q3) improved in attention/vigilance, whereas both extreme quartiles (Q1 and Q4) showed a worsening in this cognitive domain over time. Patients with lower FT4 (Q1) showed poorer baseline attention; therefore, lower baseline FT4 levels predicted a poorer prognosis in terms of attention performance. Our study suggests that baseline FT4 levels are associated with changes in attention and vigilance performance over one year in FEP patients. PMID- 26805412 TI - Sleep disturbances are associated with psychotic experiences: Findings from the National Comorbidity Survey Replication. AB - Sleep disturbances have been linked to psychotic experiences in the general adult populations of multiple countries, but this association has yet to be confirmed in the United States using robust diagnostic measures. We analyzed a subsample (n=2304) of the National Comorbidity Survey Replication, and found that when compared with those who did not report any sleep problems, individuals with sleep disturbances lasting two weeks or longer over the past 12months were significantly more likely to report at least one psychotic experience during that same time frame. Specifically, difficulty falling asleep, waking up during the night, early morning awakenings, and feeling sleepy during the day were each associated with greater odds of reporting psychotic experiences over the past year after controlling for socio-demographic variables. However, only difficulty falling asleep and early morning awakenings were still significant after adjusting for DSM comorbid disorders. Reporting three or four types of sleep disturbances was especially predictive of psychotic experiences. Our findings underscore the importance of detecting and reducing sleep problems among individuals who report PE. PMID- 26805413 TI - Resilience, internalized stigma, self-esteem, and hopelessness among people with schizophrenia: Cultural comparison in Austria and Japan. AB - Resilience is becoming an important topic in people with schizophrenia since there is evidence that it increases the probability for long-term recovery. The current study investigated transcultural differences in resilience across schizophrenia patients from two different geographical regions, Austria and Japan. Another objective was to examine transcultural differences in internalized stigma, self-esteem, and hopelessness, which can be expected to be relevant in this context, as well as the interrelations between these subjective elements of recovery and symptom severity. To this end, patients from outpatient mental health services in Innsbruck, Austria (N=52) and Tokyo, Japan (N=60) as well as 137 healthy comparison subjects from both countries were included into this cross sectional study. Notably, we detected a significant country effect with markedly lower resilience (F=74.4, p<0.001) and self-esteem scores (F=226.0, p<0.001) as well as higher hopelessness scores (F=37.4, p<0.001) among Japanese subjects in general. In addition, both Austrian and Japanese patients indicated significantly lower degrees of resilience (F=57.5, p<0.001), self-esteem (F=51.8, p<0.001), and hope (F=29.5, p<0.001) compared to healthy control subjects. The inter correlations between subjective elements of recovery were comparable in size in the two patient samples, but the inter-correlations between these issues and residual symptoms of schizophrenia as objective domains of recovery were markedly higher in Austrian subjects. This suggests that schizophrenia patients from Western European and Japanese cultures may have different needs to achieve recovery. In conclusion, it will be critical to develop culture-specific psychosocial programs and to examine their feasibility and effectiveness among these patients. PMID- 26805414 TI - How sedentary are people with psychosis? A systematic review and meta-analysis. AB - OBJECTIVE: Sedentary behavior (SB) is an independent risk factor for cardiovascular disease and mortality. We conducted a meta-analysis to investigate SB levels and predictors in people with psychosis. METHOD: Major electronic databases were searched from inception till 09/2015 for articles measuring SB with a self-report questionnaire (SRQ) or objective measure (e.g. accelerometer) in people with psychosis, including schizophrenia spectrum and bipolar disorders. A random effects meta-analysis and meta regression analysis were conducted. RESULTS: Thirteen studies were eligible including 2033 people with psychosis (mean age 41.3years (range 25.1-60), 63.2% male (range 35-89%), body mass index 28.7 (range 25.9-32.1). The trim and fill analysis demonstrated people with psychosis spent 660.8min (95% CI 523.2-798.4, participants=2033) or 11.0h (95% CI 8.72-13.3) per day being sedentary. Objective measures of SB recorded significantly higher levels (p<0.001) of SB (12.6h per day, 95% CI 8.97-16.2, studies=7, participants=254) compared to self-report SB (6.85h per day, 95% CI 4.75-8.96, studies=6, participants=1779). People with psychosis engaged in significantly more SB than controls (g=1.13, 95% CI 0.496-1.77, P<0.001, n psychosis=216, n controls=159) equating to a mean difference of 2.80 (95% CI 1.47 4.1) hours per day. Multivariate meta-regression confirmed that objective measurement of SB predicted higher levels of sedentariness. CONCLUSIONS: People with psychosis engage in very high levels of sedentary behavior in their waking day and current SRQ may underestimate SB. Given that SB is an independent predictor of cardiovascular disease, future interventions specifically targeting the prevention of SB are warranted. PMID- 26805415 TI - Sensitive skin - a global challenge with upcoming solutions. PMID- 26805416 TI - Sensitive skin. AB - Sensitive skin is a clinical condition defined by the self-reported facial presence of different sensory perceptions, including tightness, stinging, burning, tingling, pain and pruritus. Sensitive skin may occur in individuals with normal skin, with skin barrier disturbance, or as a part of the symptoms associated with facial dermatoses such as rosacea, atopic dermatitis and psoriasis. Although experimental studies are still pending, the symptoms of sensitive skin suggest the involvement of cutaneous nerve fibres and neuronal, as well as epidermal, thermochannels. Many individuals with sensitive skin report worsening symptoms due to environmental factors. It is thought that this might be attributed to the thermochannel TRPV1, as it typically responds to exogenous, endogenous, physical and chemical stimuli. Barrier disruptions and immune mechanisms may also be involved. This review summarizes current knowledge on the epidemiology, potential mechanisms, clinics and therapy of sensitive skin. PMID- 26805417 TI - Effective treatment for sensitive skin: 4-t-butylcyclohexanol and licochalcone A. AB - BACKGROUND: More than 50% of adults report to suffer from sensitive skin. This common condition is characterized by subjective sensations such as prickling, burning, skin tightness or pruritus, and is often accompanied by objective symptoms like inflammation and erythema. OBJECTIVE: The objective of this study was to develop an active ingredient concept for the treatment of sensitive skin. We tested compounds regarding their potential to (i) decrease the release of proinflammatory mediators, which among others induce erythema and (ii) counteract the hyperresponsiveness of nerve fibres and, thus, exert effects on cutaneous neurosensory dysfunction. METHODS: 4-t-butylcyclohexanol, licochalcone A and acetyl dipeptide-1 cetyl ester were analysed in vitro regarding their potential to (i) decrease the release of PGE2 and activation of NFkappaB and to (ii) inhibit TRPV1 activation or the release of neuronal CGRP. To assess subjective and objective symptoms of skin sensitivity in vivo, two controlled, single-blind, randomized studies were conducted with 4-t-butylcyclohexanol and the combination with licochalcone A. RESULTS: In vitro, 4-t-butylcyclohexanol significantly reduced TRPV1 activation, while acetyl dipeptide-1 cetyl ester had no effect on receptor activation. Licochalcone A significantly decreased NFkappaB signalling and PGE2 secretion, at lower concentrations than acetyl dipeptide-1 cetyl ester. A formulation containing 4-t-butylcyclohexanol showed a significant immediate anti-stinging/anti-burning effect in vivo, and a cream base containing a combination of 4-t-butylcyclohexanol and a licochalcone A-rich licorice extract reduced shaving-induced erythema. CONCLUSION: In vitro and in vivo data indicate that the combination of the TRPV1 antagonist 4-t-butylcyclohexanol and the potent anti-inflammatory licochalcone A provide an effective active ingredient concept for the treatment of sensitive skin, as the topical application resulted in an immediate relief from symptoms such as erythema and stinging. PMID- 26805418 TI - Comparison of skin calming effects of cosmetic products containing 4-t butylcyclohexanol or acetyl dipeptide-1 cetyl ester on capsaicin-induced facial stinging in volunteers with sensitive skin. AB - OBJECTIVE: To assess and compare the skin calming effect of cosmetic products containing 4-t-butylcyclohexanol (Eucerin((r)) UltraSensitive Soothing Care Dry Skin) or acetyl dipeptide-1 cetyl ester (La Roche-Posay Toleriane((r)) Ultra Intense Soothing Care) on subjective symptoms of skin sensitivity, a controlled, single-blind, randomized split-face capsaicin-induced stinging test was conducted. METHODS: Thirty-one female test subjects, ranging from 19 to 65 years of age, with self-perceived sensitive to very sensitive skin were enrolled. After a 3-day preconditioning period with no application of facial products and positive reaction to stimulation with a 40 ppm capsaicin cream, the test products were randomly applied to either the right or left nasolabial fold. Burning severity was assessed immediately after capsaicin application, and 1, 2, 5, 10 and 15 min after application of the test products. RESULTS: All 31 subjects reported a stinging/burning sensation on both nasolabial folds after application of capsaicin. Treatment with the 4-t-butylcyclohexanol containing product resulted in significant lower values for burning/stinging after one, and two minutes post-application in comparison to the values for the acetyl dipeptide-1 cetyl ester containing product. No significant difference was determined between the two test products for the point in time with most intense burning sensation, the severity of burning and the duration of burning after capsaicin application and subsequent application of the test products. CONCLUSION: Both products alleviated capsaicin-induced burning during the first 15 min after application. A faster and more pronounced soothing effect in vivo was demonstrated for the 4-t butylcyclohexanol containing cosmetic product in comparison to the acetyl dipeptide-1 cetyl ester containing cosmetic formulation. PMID- 26805419 TI - Skin compatibility and efficacy of a cosmetic skin care regimen with licochalcone A and 4-t-butylcyclohexanol in patients with rosacea subtype I. AB - BACKGROUND: Patients with rosacea often show facial sensitivity to cosmetics or skin care products that can influence the severity of symptoms and exacerbate erythema and inflammation. Nevertheless, special skin care is necessary to address cosmetic concerns and reduce the potential side-effects of topical or oral treatment of the disease. Appropriate skin care should comprise gentle cleansing, effective moisturization, soothing actives, UV protection and concealing pigments to help neutralize the appearance of redness. OBJECTIVE: To determine the compatibility and efficacy of a skin care regimen (consisting of a cleanser, a day care with SPF25 and a night care) containing licochalcone A (Lic A), an anti-irritant from the licorice plant Glycyrrhiza inflata, and 4-t butylcyclohexanol (SymSitive((r)) ), a substance which acts as a sensitivity regulator, in female subjects with clinically determined subtype I rosacea. METHODS: Thirty-two test subjects with mild to moderate rosacea used the skin care regimen daily for 8 weeks. Clinical assessment of erythema, subjective irritation and clinical photography were performed at baseline and after 4 and 8 weeks. Additionally, a quality-of-life questionnaire was filled out by the test subjects at baseline and week 8. The subjects completed a self-assessment questionnaire on product properties after 4 and 8 weeks of product use. RESULTS: Clinical assessments and subject response confirmed very good tolerability of the regimen, a statistically significant improvement in clinical grading for erythema and tactile roughness at weeks 4 and 8 and on telangiectasia at week 8 when compared to baseline scores. A statistically significant improvement in facial redness (a*) values, based on the L*a*b* colorimetric system, was determined at week 4 and 8 in comparison to baseline. No difference in corneometric measurement was detected at week 4 and 8 compared to baseline. CONCLUSION: The skin care regimen was found to be highly compatible with the sensitive facial skin of patients with rosacea subtype I and effective in improving signs of rosacea. Therefore, the daily use of skin care products containing LicA and SymSitive((r)) in patients with rosacea improves the overall skin appearance and the quality of life of these patients. PMID- 26805421 TI - Epigenetic modifications by inhibiting histone deacetylases reverse memory impairment in insulin resistance induced cognitive deficit in mice. AB - Insulin resistance has been reported as a strong risk factor for Alzheimer's disease. However the molecular mechanisms of association between these still remain elusive. Various studies have highlighted the involvement of histone deacetylases (HDACs) in insulin resistance and cognitive deficits. Thus, the present study was designed to investigate the possible neuroprotective role of HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA) in insulin resistance induced cognitive impairment in mice. Mice were subjected to either normal pellet diet (NPD) or high fat diet (HFD) for 8 weeks. HFD fed mice were treated with SAHA at 25 and 50 mg/kg i.p. once daily for 2 weeks. Serum insulin, glucose, triglycerides, total cholesterol and HDL-cholesterol levels were measured. A battery of behavioral parameters was performed to assess cognitive functions. Level of tumour necrosis factor (TNF-alpha) was measured in hippocampus to assess neuroinflammation. To further explore the molecular mechanisms we measured the histone H3 acetylation and brain derived neurotrophic factor (BDNF) level. HFD fed mice exhibit characteristic features of insulin resistance. These mice also showed a severe deficit in learning and memory along with reduced histone H3 acetylation and BDNF levels. In contrast, the mice treated with SAHA showed significant and dose dependent improvement in insulin resistant condition. These mice also showed improved learning and memory performance. SAHA treatment ameliorates the HFD induced reduction in histone H3 acetylation and BDNF levels. Based upon these results, it could be suggested that HDAC inhibitors exert neuroprotective effects by increasing H3 acetylation and subsequently BDNF level. PMID- 26805420 TI - Rapamycin ameliorates cadmium-induced activation of MAPK pathway and neuronal apoptosis by preventing mitochondrial ROS inactivation of PP2A. AB - Cadmium (Cd) is a highly toxic metal that affects the central nervous system. Recently we have demonstrated that inhibition of mTOR by rapamycin rescues neuronal cells from Cd-poisoning. Here we show that rapamycin inhibited Cd induced mitochondrial ROS-dependent neuronal apoptosis. Intriguingly, rapamycin remarkably blocked phosphorylation of JNK, Erk1/2 and p38 in neuronal cells induced by Cd, which was strengthened by co-treatment with Mito-TEMPO. Inhibition of JNK and Erk1/2 by SP600125 and U0126, respectively, potentiated rapamycin's prevention from Cd-induced apoptosis. Consistently, over-expression of dominant negative c-Jun or MKK1 also potently improved the inhibitory effect of rapamycin on Cd neurotoxicity. Furthermore, pretreatment with SP600125 or U0126, or expression of dominant negative c-Jun or MKK1 enhanced the inhibitory effects of rapamycin or Mito-TEMPO on Cd-induced ROS. Further investigation found that co treatment with Mito-TEMPO/rapamycin more effectively rescued cells by preventing Cd inactivation of PP2A than treatment with rapamycin or Mito-TEMPO alone. Over expression of wild-type PP2A reinforced rapamycin or Mito-TEMPO suppression of activated JNK and Erk1/2 pathways, as well as ROS production and apoptosis in neuronal cells in response to Cd. The findings indicate that rapamycin ameliorates Cd-evoked neuronal apoptosis by preventing mitochondrial ROS inactivation of PP2A, thereby suppressing activation of JNK and Erk1/2 pathways. Our results underline that rapamycin may have a potential in preventing Cd induced oxidative stress and neurodegenerative diseases. PMID- 26805425 TI - Morality is about values and character. A commentary on Backstrom and Nykanen (2016). Collectivity, evil and the dynamics of moral value. PMID- 26805423 TI - A single dose of hypnotic corrects sleep and EEG abnormalities in symptomatic Huntington's disease mice. AB - Sleep and electroencephalogram abnormalities are prominent early features of Huntington's disease (HD) that typically appear before the onset of characteristic motor symptoms. The changes in sleep and electroencephalogram seen in HD patients are largely recapitulated in mouse models of HD such as transgenic R6/2 lines. To test whether or not drugs with hypnotic properties can correct the sleep and electroencephalogram abnormalities seen in HD mice, we treated male wild-type (WT; N = 7) and R6/2 mice (N = 9) acutely with intraperitoneal injections of vehicle, zolpidem (5, 10 or 20 mg/kg) or amitriptyline (5, 10 or 20 mg/kg), and then monitored their sleep-wake behavior. In R6/2 mice, both zolpidem and amitriptyline suppressed the abnormally high REM sleep amount and electroencephalographic gamma (30-46 Hz) oscillations in a dose-dependent manner. Amitriptyline's effect on sleep was similar in both genotypes, whereas zolpidem showed significant genotype differences. Zolpidem exerted a strong hypnotic effect in WT mice by increasing electroencephalographic delta power, doubling the mean bout duration and the total amount of non-rapid eye movement sleep. However, no such effect was seen in R6/2 mice. Our study demonstrates that the pathophysiological changes seen in sleep and electroencephalogram are not 'hard wired' in HD brain and can be reversed even at late stages of the disease. The diminished hypnotic effect of zolpidem suggests that the GABAergic control of sleep-wake states is impaired in HD mice. A better understanding of the neurochemical basis underlying these abnormalities should lead to more effective and rational therapies for HD. PMID- 26805426 TI - Peptide microarray patterning for controlling and monitoring cell growth. AB - The fate of cells is influenced by their microenvironment and many cell types undergo differentiation when stimulated by extracellular cues, such as soluble growth factors and the insoluble extracellular matrix (ECM). Stimulating differentiation by insoluble or "immobilized" cues is a particularly attractive method because it allows for the induction of differentiation in a spatially defined cohort of cells within a larger subpopulation. To improve the design of de novo screening of such insoluble factors, we describe a methodology for producing high-density peptide microarrays suitable for extended cell culture and fluorescence microscopy. As a model, we used a murine mammary gland cell line (NMuMG) that undergoes epithelial to mesenchymal transition (EMT) in response to soluble transforming growth factor beta (TGF-beta) and surface-immobilized peptides that target TGF-beta receptors (TGFbetaRI/II). We repurposed a well established DNA microarray printing technique to produce arrays of micropatterned surfaces that displayed TGFbetaRI/II-binding peptides and integrin binding peptides. Upon long-term culture on these arrays, only NMuMG cells residing on EMT-stimulating areas exhibited growth arrest and decreased E-cadherin expression. We believe that the methodology created in this report will aid the development of peptide-decorated surfaces that can locally stimulate defined cell surface receptors and control EMT and other well-characterized differentiation events. STATEMENT OF SIGNIFICANCE: Scope of work: This manuscript aims to accelerate the development of instructive biomaterials decorated with specific ligands that target cell-surface receptors and induce specific differentiation of cells upon contact. These materials can be used for practical applications, such as fabricating synthetic materials for large scale, stem cell culture, or investigating differentiation and asymmetric division in stem cells. Specifically, in this manuscript, we repurposed a DNA microarray printer to produce microarrays of peptide-terminated self-assembled monolayers (SAMs). To demonstrate the utility of these arrays in phenotypic assays with mammalian cells, we monitored the induction of epithelial to mesenchymal transition (EMT) in murine mammary epithelial cells using specific peptide ligands printed on these arrays. Novelty: We, and others, have published several strategies for producing peptide-based arrays suitable for long-term phenotypic assays. Many reports relied on patterning steps that made adaptation difficult. The use of a DNA microarray printer as the sole production tool simplified the production of peptide microarrays and increased the throughput of this technology. We confirmed that simplification in production did not compromise the performance of the array; it is still possible to study short-term adhesion, long-term growth, and complex phenotypic responses, such as EMT, in the cells. EMT was studied using immunofluorescent staining after four days of culture. IMPACT: This methodology will serve as a foundation for future screening of instructive biomaterials in our research group. As DNA printers are broadly available in academic institutions, we foresee rapid adaptation of this approach by academic researchers. PMID- 26805422 TI - Binge ethanol exposure increases the Kruppel-like factor 11-monoamine oxidase (MAO) pathway in rats: Examining the use of MAO inhibitors to prevent ethanol induced brain injury. AB - Binge drinking induces several neurotoxic consequences including oxidative stress and neurodegeneration. Because of these effects, drugs which prevent ethanol induced damage to the brain may be clinically beneficial. In this study, we investigated the ethanol-mediated KLF11-MAO cell death cascade in the frontal cortex of Sprague-Dawley rats exposed to a modified Majchowicz 4-day binge ethanol model and control rats. Moreover, MAO inhibitors (MAOIs) were investigated for neuroprotective activity against binge ethanol. Binge ethanol treated rats demonstrated a significant increase in KLF11, both MAO isoforms, protein oxidation and caspase-3, as well as a reduction in BDNF expression in the frontal cortex compared to control rats. MAOIs prevented these binge ethanol induced changes, suggesting a neuroprotective benefit. Neither binge ethanol nor MAOI treatment significantly affected protein expression levels of the oxidative stress enzymes, SOD2 or catalase. Furthermore, ethanol-induced antinociception was enhanced following exposure to the 4-day ethanol binge. These results demonstrate that the KLF11-MAO pathway is activated by binge ethanol exposure and MAOIs are neuroprotective by preventing the binge ethanol-induced changes associated with this cell death cascade. This study supports KLF11-MAO as a mechanism of ethanol-induced neurotoxicity and cell death that could be targeted with MAOI drug therapy to alleviate alcohol-related brain injury. Further examination of MAOIs to reduce alcohol use disorder-related brain injury could provide pivotal insight to future pharmacotherapeutic opportunities. PMID- 26805427 TI - Novel bone wax based on poly(ethylene glycol)-calcium phosphate cement mixtures. AB - Classic bone wax is associated with drawbacks such as the risk of infection, inflammation and hindered osteogenesis. Here, we developed a novel self-setting bone wax on the basis of hydrophilic poly(ethylene glycol) (PEG) and hydroxyapatite (HA) forming calcium phosphate cement (CPC), to overcome the problems that are linked to the use of conventional beeswax systems. Amounts of up to 10 wt.% of pregelatinized starch were additionally supplemented as hemostatic agent. After exposure to a humid environment, the PEG phase dissolved and was exchanged by penetrating water that interacted with the HA precursor (tetracalcium phosphate (TTCP)/monetite) to form highly porous, nanocrystalline HA via a dissolution/precipitation reaction. Simultaneously, pregelatinized starch could gel and supply the bone wax with liquid sealing features. The novel bone wax formulation was found to be cohesive, malleable and after hardening under aqueous conditions, it had a mechanical performance (~2.5 MPa compressive strength) that is comparable to that of cancellous bone. It withstood systolic blood pressure conditions for several days and showed antibacterial properties for almost one week, even though 60% of the incorporated drug vancomycin hydrochloride was already released after 8h of deposition by diffusion controlled processes. STATEMENT OF SIGNIFICANCE: The study investigated the development of alternative bone waxes on the basis of a hydroxyapatite (HA) forming calcium phosphate cement (CPC) system. Conventional bone waxes are composed of non biodegradable beeswax/vaseline mixtures that are often linked to infection, inflammation and hindered osteogenesis. We combined the usage of bioresorbable polymers, the supplementation with hemostatic agents and the incorporation of a mineral component to overcome those drawbacks. Self-setting CPC precursors (tetracalcium phosphate (TTCP), monetite) were embedded in a resorbable matrix of poly(ethylene glycol) (PEG) and supplemented with pregelatinized starch. This formulation was found to be malleable and cohesive underwater. While immersion in an aqueous environment, CPC precursors formed highly porous, nanocrystalline HA via dissolution/precipitation reaction as water penetrated the novel wax formulation and PEG molecules simultaneously dissolved. The bone wax further withstood blood pressure conditions. After hardening, mechanical performance was comparable to that of cancellous bone and we also successfully provided the bone wax with antibacterial properties. In our opinion, the described bone wax formulation outmatches conventional bone waxes, as it circumvents the detriments being associated with the term "bone wax". Our wax has a novel composition and would broaden the application of CPC and besides, the general interest in bone waxes will increase, as they were long considered as a "first-line treatment" to avoid. PMID- 26805428 TI - Bacteria-targeted biomaterials: Glycan-coated microspheres to bind Helicobacter pylori. AB - Gastric cancer is the third leading cause of cancer related deaths worldwide and Helicobacter pylori (H. pylori) persistent infection has been pointed as a causative agent of this disease. Current antibiotic based treatments to eradicate this bacterium fail in 20% of the patients, potentially leaving 140 million people in the world without alternative therapy. It is herein proposed the use of azide-alkyne coupling ("click chemistry") to produce glycan-coated mucoadhesive microspheres that bind and remove the H. pylori adherent to the gastric mucosa through specific bacterial adhesin-glycan interactions. Glycan immobilization is performed via chitosan's primary alcohol group, rather than the more reactive primary amines in order to preserve the amine groups that confer chitosan its mucoadhesiveness. It is shown that chitosan microspheres decorated with Lewis b glycans (Leb-Mic) bind specifically to H. pylori strains expressing the BabA adhesin (strains recognized as highly pathogenic) (~230 bacteria/microsphere), are non-cytotoxic, are retained in the stomach of C57BL/6 mice for around 1.5h. Also, these Leb-Mic are able to prevent and remove H. pylori adhesion to gastric mucosa expressing the same glycan, in tissue sections from mice and human gastric mucosa (in vitro) and in fresh mice stomachs (ex vivo). These results provide proof-of-concept on the potential of glycan-decorated microspheres as an innovative therapeutic strategy against H. pylori and highlight the prospective of using targeted biomaterials to fight gastrointestinal infection. STATEMENT OF SIGNIFICANCE: Gastric cancer has been associated with persistent infection by Helicobacter pylori, a bacterium that colonizes half of world population and whose available antibiotic treatment fails in 20% of cases. H. pylori adhesion to gastric epithelium is mediated between bacterial adhesins and glycans expressed in gastric mucosa. We demonstrate that these glycans can be immobilized in a controlled orientation into mucoadhesive chitosan microspheres, making them selective for different H. pylori strains. Efficacy studies (in vitro and ex vivo) with mice and human gastric mucosa that express the same glycan, revealed microspheres capacity to remove/prevent specific H. pylori adhesion, envisaging their future application as bacteria scavenging from stomach. This bacteria binding strategy can be extrapolated to target other cells/bacteria using suitable ligands. PMID- 26805429 TI - A double-network poly(NE-acryloyl L-lysine)/hyaluronic acid hydrogel as a mimic of the breast tumor microenvironment. AB - To mimic the structure of breast tumor microenvironment, novel double-network poly(NE-acryloyl L-lysine)/hyaluronic acid (pLysAAm/HA) hydrogels were fabricated by a two-step photo-polymerization process for in vitro three-dimensional (3D) cell culture. The morphology, mechanical properties, swelling and degradation behaviors of pLysAAm/HA hydrogels were investigated. The growth behavior and function of MCF-7 cells cultured on the hydrogels and standard 2D culture plates were compared. The results showed that pLysAAm/HA hydrogels had a highly porous microstructure with a double network and that their mechanical properties, swelling ratio and degradation rate depended on the degree of methacrylation of HA. The results of in vitro studies revealed that the pLysAAm/HA hydrogels could support MCF-7 cell adhesion, promote cell proliferation, and induce the diversification of cell morphologies and overexpression of VEGF, IL-8 and bFGF. The MCF-7 cells cultured on 3D hydrogels showed significantly increased migration and invasion abilities as compared to 2D-cultured cells. Preliminary in vivo results confirmed that the 3D culture of MCF-7 cells resulted in greater tumorigenesis than their 2D culture. These results indicate that the pLysAAm/HA hydrogels can provide a 3D microenvironment for MCF-7 cells that is more representative of the in vivo breast cancer. STATEMENT OF SIGNIFICANCE: Traditional 2D cell cultures cannot ideally represent their in vivo physiological conditions. In this work, we reported a method for preparing double-network poly(NE-acryloyl L-lysine)/hyaluronic acid hydrogel, and demonstrated its suitability for use in mimicing breast tumor microenvironment. Results showed the prepared hydrogels had controllable mechanical properties, swelling ratio and degradation rate. The MCF-7 cells cultured in hydrogels expressed much higher levels of pro-angiogenic growth factors and displayed significantly enhanced migration and invasion abilities. The tumorigenic capability of MCF-7 cells pre cultured in 3D hydrogels was enhanced significantly. Therefore, the novel hydrogel may provide a more physiologically relevant 3D in vitro model for breast cancer research. To our knowledge, this is the first report assessing a HA-based double-network hydrogel used as a tumor model. PMID- 26805430 TI - Fullerenes in asphaltenes and other carbonaceous materials: natural constituents or laser artifacts. AB - The presence of fullerenes as natural constituents of carbonaceous materials or their formation as laser artifacts during laser desorption ionization (LDI) mass spectrometry (MS) analysis is reinvestigated and reviewed. The results using asphaltene samples with varying composition as well as standard polycyclic aromatic hydrocarbons (PAH) and fullerene samples as models have demonstrated that indeed Cn ring fullerenes are not natural constituents but they are formed as common and often as predominant artifacts upon laser radiation, and a series of incorrect assignments based on LDI-MS data of several carbonaceous materials seems unfortunately to have been made. When the present results are evaluated also in the light of the vast literature on LDI-MS of carbonaceous materials, the formation of fullerene artifacts seems particularly common for LDI-MS analysis of asphaltenes and other carbonaceous samples with considerably high levels of PAH and varies according to the type of laser used, and the intensity of the laser beam. PMID- 26805431 TI - Is physical activity a part of who I am? A review and meta-analysis of identity, schema and physical activity. AB - Two parallel literatures on the physical activity (PA) identity and schema constructs have the potential to supplement traditional social cognitive approaches used for PA promotion. The purpose of this paper was to review schema/identity research and appraise its relationship with PA via meta-analysis followed by thematic analyses of its correlates, as well as its proposed mechanisms on PA. Eligible studies were from English, peer-reviewed published articles that examined identity and/or schema in the context of PA. Searches were completed in June 2015 in five databases. Sixty-two independent data-sets (32 available for meta-analysis), primarily of modest quality, were identified. Results of the random effects meta-analysis showed that the point-estimate between identity/schema and behaviour was r = .44 (CI = .39-.48), and invariant to selected study characteristics. Thematic review showed that identity/schema was associated with commitment, ability, affective judgments, identified/integrated regulation and social comparison and predicted intention, self-regulatory efficacy, and self-regulation strategy use. It had reliable evidence as a moderator of the intention-behavior relationship, was associated with increases in the speed of processing of relevant information and created negative affect under hypothetical identity-behavior discrepant situations. While this initial research is promising, more rigorous research designs, including interventions to increase identity/schema, are warranted. PMID- 26805433 TI - Oral Inosine Persistently Elevates Plasma antioxidant capacity in Parkinson's disease. AB - INTRODUCTION: Higher serum urate predicts slower progression in PD. The aim of this work was to assess whether oral inosine alters antioxidant capacity of plasma or CSF or urinary markers of oxidative injury in early PD. METHODS: We assayed plasma and CSF antioxidant capacity by ferric-reducing antioxidant power and measured DNA oxidation adduct 8-hydroxydeoxyguanosine from urine in Safety of URate Elevation in PD, a randomized, placebo-controlled trial of oral inosine assessing safety of elevating serum urate from <6 mg/dL to 6.1-7.0 or 7.1-8.0 mg/dL in patients with early PD. RESULTS: At 6 months, antioxidant capacity was 29% higher among mild and 43% higher among moderate group participants compared to placebo and correlated with change in serum urate (r = 0.86) and inversely with rate of clinical decline (r = -0.26). CSF antioxidant capacity and urine 8 hydroxydeoxyguanosine did not differ. CONCLUSIONS: The findings demonstrate a dose-dependent, persistent elevation of plasma antioxidant capacity from oral inosine of potential therapeutic relevance. PMID- 26805432 TI - Markers of cellular senescence. Telomere shortening as a marker of cellular senescence. AB - The cellular senescence definition comes to the fact of cells irreversible proliferation disability. Besides the cell cycle arrest, senescent cells go through some morphological, biochemical, and functional changes which are the signs of cellular senescence. The senescent cells (including replicative senescence and stress-induced premature senescence) of all the tissues look alike. They are metabolically active and possess the set of characteristics in vitro and in vivo, which are known as biomarkers of aging and cellular senescence. Among biomarkers of cellular senescence telomere shortening is a rather elegant frequently used biomarker. Validity of telomere shortening as a marker for cellular senescence is based on theoretical and experimental data. PMID- 26805434 TI - Pontocerebellar hypoplasia type 2D and optic nerve atrophy further expand the spectrum associated with selenoprotein biosynthesis deficiency. AB - BACKGROUND: The term Pontocerebellar hypoplasias collectively refers to a group of rare, heterogeneous and progressive disorders, which are frequently inherited in an autosomal recessive manner and usually have a prenatal onset. Mutations in the SEPSECS gene, leading to deficiency in selenoprotein biosynthesis, have been identified in recent times as the molecular etiology of different pre/perinatal onset neurological phenotypes, including cerebello-cerebral atrophy, Pontocerebellar hypoplasia type 2D and progressive encephalopathy with elevated lactate. These disorders share a similar spectrum of central (e.g., brain neurodegeneration with grey and white matter both involved) and peripheral (e.g., spasticity due to axonal neuropathy) nervous system impairment. CASE PRESENTATION: We hereby describe a 9-year-old boy with (i) a typical Pontocerebellar hypoplasia type 2D phenotype (e.g. profound mental retardation, spastic quadriplegia, ponto-cerebellar hypoplasia and progressive cerebral atrophy); (ii) optic nerve atrophy and (iii) mild secondary mitochondrial myopathy detected by muscle biopsy and respiratory chain enzyme analysis. We performed whole exome sequencing which identified a homozygous mutation of the SEPSECS gene (c.1001T > C), confirming the clinical suspect of Pontocerebellar hypoplasia type 2D. CONCLUSION: This report further corroborates the notion of a potential secondary mitochondrial dysfunction in the context of selenoprotein biosynthesis deficiency and also adds optic nerve atrophy as a new potential clinical feature within the SEPSECS-associated clinical spectrum. These findings suggest the presence of a possible shared genetic etiology among similar clinical entities characterized by the combination of progressive cerebello-cerebral and optic nerve atrophy and also stress the biological importance of selenoproteins in the regulation of neuronal and metabolic homeostasis. PMID- 26805435 TI - Safety and pharmacokinetic profile of rufinamide in pediatric patients aged less than 4 years with Lennox-Gastaut syndrome: An interim analysis from a multicenter, randomized, active-controlled, open-label study. AB - OBJECTIVE: A good knowledge of safety and age group-specific pharmacokinetics (PK) of antiepileptic drugs (AEDs) in young pediatric patients is of great importance in clinical practice. This paper presents 6-month interim safety and PK from an ongoing 2-year open-label study (Study 303) of adjunctive rufinamide treatment in pediatric subjects >= 1 to < 4 years with inadequately controlled epilepsies of the Lennox-Gastaut syndrome (LGS) spectrum. METHODS: Subjects (N = 37) were randomized to either rufinamide or any other approved AED chosen by the investigator as adjunctive therapy to the subject's existing regimen of 1-3 AEDs. RESULTS: Interim safety results showed that treatment-emergent adverse events (TEAEs) were similar between the rufinamide (22 [88.0%]) and any-other-AED group (9 [81.8%]), with most events considered mild or moderate. A population PK analysis was conducted including plasma rufinamide concentrations from Study 303 and two other study populations of LGS subjects >= 4 years. The rufinamide PK profile was dose independent. The apparent clearance (CL/F) estimated from the PK model was 2.19 L/h; it was found to increase significantly as a function of body weight. Coadministration of valproic acid significantly decreased rufinamide CL/F. CL/F was not significantly affected by other concomitant AEDs, age, gender, race, hepatic function, or renal function. No adjustments to body weight-based rufinamide dosing in subjects >= 1 to < 4 years are necessary. SIGNIFICANCE: Rufinamide was safe and well tolerated in these pediatric subjects. Results from the interim analysis demonstrate that rufinamide's safety and PK profile is comparable in subjects >= 1 to < 4 and >= 4 years with LGS. CLINICAL TRIAL REGISTRATION: Study 303 (clinicaltrials.gov: NCT01405053). PMID- 26805436 TI - Editorial: Investigate the Functions of Chemicals Through Heterogeneous Network of Chemicals and Proteins. PMID- 26805438 TI - Step dynamics and oxide formation during CO oxidation over a vicinal Pd surface. AB - In an attempt to bridge the material and pressure gaps - two major challenges for an atomic scale understanding of heterogeneous catalysis - we employed high energy surface X-ray diffraction as a tool to study the Pd(553) surface in situ under changing reaction conditions during CO oxidation. The diffraction patterns recorded under CO rich reaction conditions are characteristic for the metallic state of the surface. In an environment with low excess of O2 over the reaction stoichiometry, the surface seems to accommodate oxygen atoms along the steps forming one or several subsequent adsorbate structures and rapidly transforms into a combination of (332), (111) and (331) facets likely providing the room for the formation of a surface oxide. For the case of large excess of O2, the diffraction data show the presence of a multilayer PdO with the [101] crystallographic direction parallel to the [111] and the [331] directions of the substrate. The reconstructions in O2 excess are to a large extent similar to those previously reported for pure O2 exposures by Westerstrom et al. [R. Westerstrom et al., Phys. Rev. B: Condens. Matter Mater. Phys., 2007, 76, 155410]. PMID- 26805437 TI - The complete mitochondrial genome of Metorchis orientalis (Trematoda: Opisthorchiidae): Comparison with other closely related species and phylogenetic implications. AB - Metorchis orientalis (Trematoda: Opisthorchiidae) is an important trematode infecting many animals and humans, causing metorchiasis. In the present study, the complete mitochondrial (mt) genome of M. orientalis was sequenced. The complete mt genome of M. orientalis is 13,834 bp circular DNA molecule and contains 12 protein-coding genes, 22 transfer RNA genes, and two ribosomal RNA genes. The gene content and arrangement of M. orientalis is the same as those of Opisthorchiidae trematodes (Opisthorchis viverrini, Opisthorchis felineus and Clonorchis sinensis), but distinct from Schistosoma spp. Phylogenetic analyses using concatenated amino acid sequences of 12 protein-coding genes with three different computational algorithms (Bayesian inference, maximum likelihood and maximum parsimony) revealed that M. orientalis and O. viverrini represent sister taxa. The mt genome provides a novel genetic marker for further studies of the identification, classification and molecular epidemiology of Opisthorchiidae trematodes, and should have implications for the diagnosis, prevention and control of metorchiasis in animals and humans. PMID- 26805439 TI - Structural and Electrochemical Study of Vanadium-Doped TiO2 Ramsdellite with Superior Lithium Storage Properties for Lithium-Ion Batteries. AB - Titanium-oxide-based materials are considered attractive and safe alternatives to carbonaceous anodes in Li-ion batteries. In particular, the ramsdellite form TiO2 (R) is known for its superior lithium-storage ability as the bulk material when compared with other titanates. In this work, we prepared V-doped lithium titanate ramsdellites with the formula Li0.5 Ti1-x Vx O2 (0<=x<=0.5) by a conventional solid-state reaction. The lithium-free Ti1-x Vx O2 compounds, in which the ramsdellite framework remains virtually unaltered, are easily obtained by a simple aqueous oxidation/ion-extraction process. Neutron powder diffraction is used to locate the Li channel site in Li0.5 Ti1-x Vx O2 compounds and to follow the lithium extraction by difference-Fourier maps. Previously delithiated Ti1-x Vx O2 ramsdellites are able to insert up to 0.8 Li(+) per transition-metal atom. The initial gravimetric capacities of 270 mAh g(-1) with good cycle stability under constant current discharge conditions are among the highest reported for bulk TiO2 -related intercalation compounds for the threshold of one e(-) per formula unit. PMID- 26805440 TI - An overview of X inactivation based on species differences. AB - X inactivation, a developmental process that takes place in early stages of mammalian embryogenesis, balances the sex difference in dosage of X-linked genes. Although all mammals use this form of dosage compensation, the details differ from one species to another because of variations in the staging of embryogenesis and evolutionary tinkering with the DNA blueprint for development. Such differences provide a broader view of the process than that afforded by a single species. My overview of X inactivation is based on these species variations. PMID- 26805441 TI - The potential role of telocytes in Tissue Engineering and Regenerative Medicine. AB - Research and ideas for potential applications in the field of Tissue Engineering (TE) and Regenerative Medicine (RM) have been constantly increasing over recent years, basically driven by the fundamental human dream of repairing and regenerating lost tissue and organ functions. The basic idea of TE is to combine cells with putative stem cell properties with extracellular matrix components, growth factors and supporting matrices to achieve independently growing tissue. As a side effect, in the past years, more insights have been gained into cell cell interaction and how to manipulate cell behavior. However, to date the ideal cell source has still to be found. Apart from commonly known various stem cell sources, telocytes (TC) have recently attracted increasing attention because they might play a potential role for TE and RM. It becomes increasingly evident that TC provide a regenerative potential and act in cellular communication through their network-forming telopodes. While TE in vitro experiments can be the first step, the key for elucidating their regenerative role will be the investigation of the interaction of TC with the surrounding tissue. For later clinical applications further steps have to include an upscaling process of vascularization of engineered tissue. Arteriovenous loop models to vascularize such constructs provide an ideal platform for preclinical testing of future therapeutic concepts in RM. The following review article should give an overview of what is known so far about the potential role of TC in TE and RM. PMID- 26805442 TI - The regulation of male fertility by the PTPN11 tyrosine phosphatase. AB - PTPN11 (also known as SHP2) is a ubiquitously expressed non-receptor tyrosine phosphatase that regulates cell survival, proliferation, differentiation, migration and adhesion. Naturally occurring mutations in the PTPN11 gene cause Noonan and LEOPARD syndromes, two genetic disorders that are characterized by a spectrum of defects including male infertility. This review summarizes four cellular and molecular mechanisms by which PTPN11 acts to support male fertility. First, PTPN11 is required for the proliferation and survival of spermatogonial stem cells (SSCs) that are essential to replenish the germ cells that will become sperm. Second, PTPN11 regulation of cellular adhesion functions in Sertoli cells is required to maintain the blood-testis barrier (BTB) that protects meiotic and post-meiotic germ cells. Third, expression of PTPN11 in Sertoli cells is essential to prevent premature differentiation and exhaustion of the SSC population and to maintain the SSC niche. Finally, in Leydig cells, PTPN11 supports mitochondrial fusion and the expression of acyl-CoA synthetase (ACSL4) needed for the production of steroids including testosterone, which is required for fertility. PMID- 26805443 TI - Testicular immunoregulation and spermatogenesis. AB - The mammalian testis possesses a unique immune environment that is essential for testicular function. The testis is a remarkable immunoprivileged site that protects immunogenic germ cells from the detrimental effects of immune responses. However, the testis can be infected by various microbial pathogens. To overcome the immune privilege and enable testicular defense against microbes, the testis adopts local effective innate immune responses to microbial infections. The mechanisms underlying the testicular immune privilege have been investigated for several decades and the innate defense system in the testis is being revealed based on the identification of pattern recognition receptor-initiated innate immune responses in testicular cells. The coordination between immune privilege and local innate immune responses is critical in the maintenance of testicular immune homeostasis. Disruption of the testicular immune homeostasis may lead to orchitis and impair spermatogenesis, an etiological factor of male infertility. Dissection of the immunoregulatory mechanisms in the testis can aid in establishing preventive and therapeutic approaches for orchitis. This review discusses current understanding of the mechanisms which underlie the testicular immunoregulation and its effect on spermatogenesis. PMID- 26805444 TI - Telocyte implications in human pathology: An overview. AB - Telocytes are a recently described interstitial cell population widely distributed in the stromal compartment of many organs in vertebrates, including humans. Owing to their close spatial relationship with multiple cell types, telocytes are universally considered as 'connecting cells' mostly committed to intercellular signaling by converting the interstitium into an integrated system that drives organ development and contributes to the maintenance of local tissue homeostasis. Increasing evidence indicates that telocytes may cooperate with tissue-resident stem cells to foster organ repair and regeneration, and that telocyte damage and dysfunction may occur in several disorders. The goal of this review is to provide an overview of the most recent findings concerning the implication of telocytes in a variety of pathologic conditions in humans, including heart disease, chronic inflammation and multiorgan fibrosis. Based on recent promising experimental data, there is realistic hope that by targeting telocytes alone or in tandem with stem cells, we might be able to promote organ regeneration and/or prevent irreversible end-stage organ damage in different pathologies. PMID- 26805446 TI - Effects of nanomaterials on marine invertebrates. AB - The development of nanotechnology will inevitably lead to the release of consistent amounts of nanomaterials (NMs) and nanoparticles (NPs) into marine ecosystems. Ecotoxicological studies have been carried out to identify potential biological targets of NPs, and suitable models for predicting their impact on the health of the marine environment. Recent studies in invertebrates mainly focused on NP accumulation and sub-lethal effects, rather than acute toxicity. Among marine invertebrates, bivalves represent by large the most studied group, with polychaetes and echinoderms also emerging as significant targets of NPs. However, major scientific gaps still need to be filled. In this work, factors affecting the fate of NPs in the marine environment, and their consequent uptake/accumulation/toxicity in marine invertebrates will be summarized. The results show that in different model species, NP accumulation mainly occurs in digestive tract and gills. Data on sub-lethal effects and modes of action of different types of NPs (mainly metal oxides and metal based NPs) in marine invertebrates will be reviewed, in particular on immune function, oxidative stress and embryo development. Moreover, the possibility that such effects may be influenced by NP interactions with biomolecules in both external and internal environment will be introduced. In natural environmental media, NP interactions with polysaccharides, proteins and colloids may affect their agglomeration/aggregation and consequent bioavailability. Moreover, once within the organism, NPs are known to interact with plasma proteins, forming a protein corona that can affect particle uptake and toxicity in target cells in a physiological environment. These interactions, leading to the formation of eco bio-coronas, may be crucial in determining particle behavior and effects also in marine biota. In order to classify NPs into groups and predict the implications of their release into the marine environment, information on their intrinsic properties is clearly insufficient, and a deeper understanding of NP eco/bio interactions is required. PMID- 26805445 TI - Microfluidic device for simultaneous analysis of neutrophil extracellular traps and production of reactive oxygen species. AB - Neutrophil extracellular traps (NETs) were first reported in 2004, and since their discovery, there has been an increasing interest in NETs, how they are formed, their role in controlling infections, and their contribution to disease pathogenesis. Despite this rapid expansion of our understanding of NETs, many details remain unclear including the role of reactive oxygen species (ROS) in the formation of NETs. Further, to study NETs, investigators typically require a large number of cells purified via a lengthy purification regimen. Here, we report a microfluidic device used to quantify both ROS and NET production over time in response to various stimulants, including live bacteria. This device enables ROS and NET analysis using a process that purifies primary human neutrophils in less than 10 minutes and requires only a few microliters of whole blood. Using this device we demonstrate the ability to identify distinct capabilities of neutrophil subsets (including ROS production and NET formation), the ability to use different stimulants/inhibitors, and the ability to effectively use samples stored for up to 8 hours. This device permits the study of ROS and NETs in a user-friendly format and has potential for widespread applications in the study of human disease. PMID- 26805447 TI - Developments in Earth observation for the assessment and monitoring of inland, transitional, coastal and shelf-sea waters. AB - The Earth's surface waters are a fundamental resource and encompass a broad range of ecosystems that are core to global biogeochemical cycling and food and energy production. Despite this, the Earth's surface waters are impacted by multiple natural and anthropogenic pressures and drivers of environmental change. The complex interaction between physical, chemical and biological processes in surface waters poses significant challenges for in situ monitoring and assessment and often limits our ability to adequately capture the dynamics of aquatic systems and our understanding of their status, functioning and response to pressures. Here we explore the opportunities that Earth observation (EO) has to offer to basin-scale monitoring of water quality over the surface water continuum comprising inland, transition and coastal water bodies, with a particular focus on the Danube and Black Sea region. This review summarises the technological advances in EO and the opportunities that the next generation satellites offer for water quality monitoring. We provide an overview of algorithms for the retrieval of water quality parameters and demonstrate how such models have been used for the assessment and monitoring of inland, transitional, coastal and shelf sea systems. Further, we argue that very few studies have investigated the connectivity between these systems especially in large river-sea systems such as the Danube-Black Sea. Subsequently, we describe current capability in operational processing of archive and near real-time satellite data. We conclude that while the operational use of satellites for the assessment and monitoring of surface waters is still developing for inland and coastal waters and more work is required on the development and validation of remote sensing algorithms for these optically complex waters, the potential that these data streams offer for developing an improved, potentially paradigm-shifting understanding of physical and biogeochemical processes across large scale river-sea systems including the Danube-Black Sea is considerable. PMID- 26805448 TI - GSK3beta Inhibition Promotes Efficient Myeloid and Lymphoid Hematopoiesis from Non-human Primate-Induced Pluripotent Stem Cells. AB - Advances in the scalable production of blood cells from induced pluripotent stem cells (iPSCs) open prospects for the clinical translation of de novo generated blood products, and evoke the need for preclinical evaluation of their efficacy, safety, and immunogenicity in large animal models. Due to substantial similarities with humans, the outcomes of cellular therapies in non-human primate (NHP) models can be readily extrapolated to a clinical setting. However, the use of this model is hampered by relatively low efficiency of blood generation and lack of lymphoid potential in NHP-iPSC differentiation cultures. Here, we generated transgene-free iPSCs from different NHP species and showed the efficient induction of mesoderm, myeloid, and lymphoid cells from these iPSCs using a GSK3beta inhibitor. Overall, our studies enable scalable production of hematopoietic progenitors from NHP-iPSCs, and lay the foundation for preclinical testing of iPSC-based therapies for blood and immune system diseases in an NHP model. PMID- 26805449 TI - Oleanolic acid and hederagenin glycosides from Weigela stelzneri. AB - Four previously undescribed and one known oleanolic acid glycosides were isolated from the roots of Weigela stelzneri, and one previously undescribed and three known hederagenin glycosides were isolated from the leaves. Their structures were elucidated mainly by 2D NMR spectroscopic analysis and mass spectrometry as 3-O beta-D-glucopyranosyl-(1 -> 2)-[beta-D-xylopyranosyl-(1 -> 4)]-beta-D xylopyranosyl-(1 -> 4)-beta-D-xylopyranosyl-(1 -> 3)-alpha-L-rhamnopyranosyl-(1 > 2)-alpha-L-arabinopyranosyloleanolic acid, 3-O-beta-D-glucopyranosyl-(1 -> 2) [beta-D-xylopyranosyl-(1 -> 4)]-beta-D-xylopyranosyl-(1 -> 4)-beta-D xylopyranosyl-(1 -> 3)-alpha-L-rhamnopyranosyl-(1 -> 2)-beta-D xylopyranosyloleanolic acid, 3-O-beta-D-glucopyranosyl-(1 -> 2)-[beta-D glucopyranosyl-(1 -> 4)]-beta-D-xylopyranosyl-(1 -> 4)-beta-D-xylopyranosyl-(1 -> 3)-alpha-L-rhamnopyranosyl-(1 -> 2)-beta-D-xylopyranosyloleanolic acid, 3-O-beta D-glucopyranosyl-(1 -> 2)-[beta-D-xylopyranosyl-(1 -> 4)]-beta-D-xylopyranosyl-(1 -> 4)-beta-D-xylopyranosyl-(1 -> 3)-alpha-L-rhamnopyranosyl-(1 -> 2)-alpha-L arabinopyranosyloleanolic acid 28-O-beta-D-glucopyranosyl-(1 -> 6)-beta-D glucopyranosyl ester, and 3-O-beta-D-glucopyranosyl-(1 -> 2)-alpha-L arabinopyranosylhederagenin 28-O-beta-D-xylopyranosyl-(1 -> 6)-[alpha-L rhamnopyranosyl-(1 -> 2)]-beta-D-glucopyranosyl ester. The majority of the isolated compounds were evaluated for their cytotoxicity against two tumor cell lines (SW480 and EMT-6), and for their anti-inflammatory activity. The compounds 3-O-beta-D-glucopyranosyl-(1 -> 2)-[beta-D-xylopyranosyl-(1 -> 4)]-beta-D xylopyranosyl-(1 -> 4)-beta-D-xylopyranosyl-(1 -> 3)-alpha-L-rhamnopyranosyl-(1 > 2)-alpha-L-arabinopyranosyloleanolic acid and 3-O-beta-D-glucopyranosyl-(1 -> 2)-[beta-D-xylopyranosyl-(1 -> 4)]-beta-D-xylopyranosyl-(1 -> 4)-beta-D xylopyranosyl-(1 -> 3)-alpha-L-rhamnopyranosyl-(1 -> 2)-beta-D xylopyranosyloleanolic acid exhibited the strongest cytotoxicity on both cancer cell lines. They revealed a 50% significant inhibitory effect of the IL-1beta production by PBMCs stimulated with LPS at a concentration inducing a very low toxicity of 23% and 28%, respectively. PMID- 26805451 TI - Got Big Data? PMID- 26805450 TI - Evaluation of children with ADHD on the Ball-Search Field Task. AB - Searching, defined for the purpose of the present study as the displacement of an individual to locate resources, is a fundamental behavior of all mobile organisms. In humans this behavior underlies many aspects of everyday life, involving cognitive processes such as sustained attention, memory and inhibition. We explored the performance of 36 treatment-free children diagnosed with attention-deficit hyperactivity disorder (ADHD) and 132 children from a control school sample on the ecologically based ball-search field task (BSFT), which required them to locate and collect golf balls in a large outdoor area. Children of both groups enjoyed the task and were motivated to participate in it. However, performance showed that ADHD-diagnosed subjects were significantly less efficient in their searching. We suggest that the BSFT provides a promising basis for developing more complex ecologically-derived tests that might help to better identify particular cognitive processes and impairments associated with ADHD. PMID- 26805452 TI - Left Atrial Expansion Index Predicts Left Ventricular Filling Pressure and Adverse Events in Acute Heart Failure With Severe Left Ventricular Dysfunction. AB - BACKGROUND: The power of left atrial (LA) parameters for predicting left ventricular (LV) filling pressure and adverse events in acute heart failure (HF) with severe LV dysfunction, either sinus rhythm or atrial fibrillation (AF), is not fully understood. METHODS AND RESULTS: Echocardiography was performed in 141 patients with acute decompensated congestive HF and LV ejection fraction <35%, including 42 with permanent AF. The LA expansion index was calculated as (Volmax Volmin) * 100%/Volmin, where Volmax was defined as maximal and Volmin as minimal LA volume. Of 141 patients, invasive LV filling pressures within 12 hours of LA expansion index measurement were available in 109. The end points were 3-year frequencies of HF hospitalization and all-cause mortality. Over a median follow up of 3.1 years, 74 participants (52.5%) reached the end points (sinus vs AF group: 48.5% vs 61.9%, respectively; P = .047). Multivariate analysis revealed that adverse events of both groups were only independently associated with age and LA expansion index. Rates of adverse events were proportional to LA expansion index. There was a good logarithmic relationship between LA expansion index and LV filling pressure, regardless of presence or absence of AF. CONCLUSIONS: LV filling pressure can be estimated well by LA expansion index, with or without AF. The LA expansion index predicts adverse events in HF patients with severe systolic dysfunction. (ClinicalTrials.gov number: NCT01307722). PMID- 26805454 TI - Behind Closed Doors: Involuntary Treatment in Care of Persons with Cognitive Impairment at Home in the Netherlands. AB - OBJECTIVES: To explore the prevalence and associated factors of involuntary treatment (physical restraints, psychotropic medication, nonconsensual care) in persons with cognitive impairment receiving home care. DESIGN: Cross-sectional survey using association analyses. SETTING: Professional home care in the southern part of the Netherlands. PARTICIPANTS: Data were collected on 837 persons with cognitive impairment (mean age 81.6; 60% female). MEASUREMENTS: Involuntary treatment was measured using a tool to identify physical restraints, psychotropic medication, and nonconsensual care. Activities of daily living (ADLs) were measured using the ADL Hierarchy subscale of the Resident Assistant Instrument-Minimum Data Set and cognitive status using the Cognitive Performance Scale. Informal caregiver burden was assessed using the Self-Perceived Pressure from Informal Care Scale. RESULTS: Involuntary treatment was used in 39% of the total sample. Most common were nonconsensual care (79%; e.g., concealing medication in food, forcing hygiene) and psychotropic medication (41%). In 7% of the sample, physical restraints (e.g., deep or overturned chair, bilateral full enclosure bedrails) were used. Caregiver burden, ADL dependency, cognitive status, living alone, and a diagnosis of dementia were strongly associated with involuntary treatment. The family of the person with cognitive impairment most often requested the use of involuntary treatment. CONCLUSION: Involuntary treatment is often used in persons with cognitive impairment receiving home care in the Netherlands. Future research should focus on understanding and preventing inappropriate involuntary treatment in home care. PMID- 26805453 TI - Virus-specific antibodies allow viral replication in the marginal zone, thereby promoting CD8(+) T-cell priming and viral control. AB - Clinically used human vaccination aims to induce specific antibodies that can guarantee long-term protection against a pathogen. The reasons that other immune components often fail to induce protective immunity are still debated. Recently we found that enforced viral replication in secondary lymphoid organs is essential for immune activation. In this study we used the lymphocytic choriomeningitis virus (LCMV) to determine whether enforced virus replication occurs in the presence of virus-specific antibodies or virus-specific CD8(+) T cells. We found that after systemic recall infection with LCMV-WE the presence of virus-specific antibodies allowed intracellular replication of virus in the marginal zone of spleen. In contrast, specific antibodies limited viral replication in liver, lung, and kidney. Upon recall infection with the persistent virus strain LCMV-Docile, viral replication in spleen was essential for the priming of CD8(+) T cells and for viral control. In contrast to specific antibodies, memory CD8(+) T cells inhibited viral replication in marginal zone but failed to protect mice from persistent viral infection. We conclude that virus-specific antibodies limit viral infection in peripheral organs but still allow replication of LCMV in the marginal zone, a mechanism that allows immune boosting during recall infection and thereby guarantees control of persistent virus. PMID- 26805456 TI - Evaluation of urinary keratan sulfate disaccharides in MPS IVA patients using UPLC-MS/MS. AB - BACKGROUND: Glycosaminoglycan analysis for the diagnosis of Morquio patients has been daunting due to lack of sensitivity/specificity of the dimethylmethylene blue-based spectrophotometry methodology, routinely used by several clinical laboratories. MS methods have been devised for quantification of keratan sulfate for Morquio patients, but some used tributylamine in mobile phases, or did not use isotope-labeled internal standards. Results & methodology: An UPLC-MS/MS methodology aiming to solve these issues was devised, based on the digestion of keratan sulfate to obtain two major disaccharides. Abnormal urinary results were obtained for all Morquio A patients, while the dimethylmethylene blue-based spectrophotometry methodology showed normal results for four out of nine cases. CONCLUSION: The devised method is sensitive, specific and suitable for high-risk screening and longitudinal evaluation of treated patients. PMID- 26805457 TI - The immunosuppressive effect of domain-deleted dimer of HLA-G2 isoform in collagen-induced arthritis mice. AB - HLA-G is involved in maternal-fetal immune tolerance and is reported to be a natural tolerogenic molecule. Seven-spliced isoforms including dimeric and beta2m free forms have been identified. The major isoform, HLA-G1 (and its soluble type HLA-G5), binds to the inhibitory immune receptors, leukocyte immunoglobulin (Ig) like receptor (LILR) B1 and LILRB2. We previously reported that HLA-G1 also binds to paired Ig-like receptor (PIR)-B, a mouse homolog of LILRBs, and had a significant immunosuppressive effect in collagen-induced arthritis (CIA) mice. Although HLA-G2 and its soluble form HLA-G6 bind specifically to LILRB2, its functional characteristics are largely unknown. In this study, we report the significant immunosuppressive effect of HLA-G2 dimer in CIA mice. Surface plasmon resonance analysis revealed a specific interaction of HLA-G2 with PIR-B. CIA mice were administered HLA-G2 protein subcutaneously once in the left footpad and clinical severity was evaluated in a double-blind study. A single administration of HLA-G2 maintained a suppressive effect for over 1month. These results suggested that the HLA-G2 protein might be a useful biopharmaceutical for the treatment of rheumatoid arthritis by binding to inhibitory PIR-B. PMID- 26805458 TI - KIR and HLA genotyping of Japanese descendants from Curitiba, a city of predominantly European ancestry from Southern Brazil. AB - We hereby report the KIR gene frequencies and the frequencies of HLA ligands of KIR for Brazilians of Japanese ancestry. A total of 51 individuals were genotyped for presence/absence of KIR (killer cell immunoglobulin-like receptors) genes and presence of HLA (human leukocyte antigens) ligands. KIR was genotyped using two pairs of sequence-specific primers (PCR-SSP) and HLA ligands were typed by LABType(r) SSO reagent kits (One Lambda, USA). These data are fully available in Allele Frequencies Net Database, under the population name "Brazil Curitiba Japanese KIR". PMID- 26805459 TI - A multi-agent cell-based model for wound contraction. AB - A mathematical model for wound contraction is presented. The model is based on a cell-based formalism where fibroblasts, myofibroblasts and the immune reaction are taken into account. The model is used to simulate contraction of a wound using point forces on the cell boundary and it also determines the orientation of collagen after restoration of the damage. The paper presents the mathematical model in terms of the equations and assumptions, as well as some implications of the modelling. The present model predicts that the amount of final contraction is larger if the migration velocity of the leukocytes is larger and hence it is important that the immune system functions well to prevent contractures. Further, the present model is the first cell-based model that combines the immune system to final contractions. PMID- 26805461 TI - Fetal and maternal cardiac responses to physical activity and exercise during pregnancy. AB - Since the 1970s, researchers have studied the influence of exercise during pregnancy on offspring heart development. With the knowledge and current evidence of fetal programming effects, research has demonstrated that exercise is safe and beneficial for mother, fetus, and neonate. Predominantly, research has focused on maternal and fetal cardiac adaptations related to aerobic exercise during pregnancy; less is known regarding the effects of resistance or combination (aerobic and resistance) training during pregnancy. Ongoing research is focusing on fetal responses to different intensity, duration and modes of maternal exercise throughout pregnancy. This article will summarize our current state of knowledge regarding the influence of exercise intensity, duration, and modes during pregnancy on maternal and fetal cardiac responses. PMID- 26805460 TI - Sagittal plane rotation center of lower lumbar spine during a dynamic weight lifting activity. AB - This study investigated the center of rotation (COR) of the intervertebral segments of the lower lumbar spine (L4-L5 and L5-S1 segments) in sagittal plane during a weight-lifting (3.6 kg in each hand) extension activity performed with the pelvis constrained. Seven healthy subjects were studied using a dual fluoroscopic imaging technique. Using the non-weightbearing, supine position during MRI scan as a reference, the average intervertebral flexion angles of the L4-L5 and L5-S1 were 6.6 degrees and 5.3 degrees at flexion position of the body, respectively, and were -1.8 degrees and -3.5 degrees at extension position of the body, respectively. The CORs of the lower lumbar spine were found segment-dependent and changed with the body postures. The CORs of the L4-L5 segment were at the location about 75% posterior from the anterior edge of the disc at flexion positions of the body, and moved to about 92% of the posterior portion of the disc at extension positions of the body. The CORs of the L5-S1 segment were at 95% posterior portion of the disc at flexion positions of the body, and moved outside of the posterior edge of the disc by about 12% of the disc length at extension positions of the body. These results could help understand the physiological motion characters of the lower lumbar spine. The data could also provide important insights for future improvement of artificial disc designs and surgical implantation of the discs that are aimed to reproduce normal spinal functions. PMID- 26805462 TI - Single-ion adsorption and switching in carbon nanotubes. AB - Single-ion detection has, for many years, been the domain of large devices such as the Geiger counter, and studies on interactions of ionized gasses with materials have been limited to large systems. To date, there have been no reports on single gaseous ion interaction with microelectronic devices, and single neutral atom detection techniques have shown only small, barely detectable responses. Here we report the observation of single gaseous ion adsorption on individual carbon nanotubes (CNTs), which, because of the severely restricted one dimensional current path, experience discrete, quantized resistance increases of over two orders of magnitude. Only positive ions cause changes, by the mechanism of ion potential-induced carrier depletion, which is supported by density functional and Landauer transport theory. Our observations reveal a new single ion/CNT heterostructure with novel electronic properties, and demonstrate that as electronics are ultimately scaled towards the one-dimensional limit, atomic-scale effects become increasingly important. PMID- 26805463 TI - Reconstruction of 56 mandibular defects with autologous compressed particulate corticocancellous bone grafts. AB - We retrospectively evaluated the results of particulate corticocancellous bone grafting of mandibular defects. Patients with deficits of mandibular continuity as a result of injuries or resection of disease had the affected segment debrided or resected, followed by placement of a patient-specific reconstruction plate. Eight weeks after resection, it was reconstructed with an autotransplant from the posterior iliac crest. Grafts were deemed successful if the regenerated ossicle (after 6 months' maturation) was adequate to take an osseointegrated fixture at least 10mm long. Fifty-six patients were treated, of whom 5 were lost to follow up. The remaining 51 patients were followed up for a mean (SD) of 29 (18) months. The mean (SD) length of the defect was 12.4 (8.4) cm. Of the 51 reconstructions, 43 healed uneventfully and the grafts were deemed successful. Two healed grafts developed recurrent tumour, which required resection of the entire reconstructed area in one, and partial resection in the other. Three patients lost the complete graft from sepsis, and five developed sepsis that required debridement with partial loss of the graft. Two patients in the latter group required a second graft. One patient required an augmentation graft, as the ossicle was not sufficient to take an implant. The technique of staged grafting with particulate corticocancellous bone after moulding of the recipient site with a spacer produces unmatched restitution of mandibular anatomy with low morbidity. PMID- 26805466 TI - PI3K/Akt pathway contributes to neuroprotective effect of Tongxinluo against focal cerebral ischemia and reperfusion injury in rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo (TXL), a compound prescription, is formulated according to the collateral disease doctrine of traditional Chinese medicine, and is widely used for the treatment of cardio-cerebrovascular diseases in China. AIM OF THE STUDY: We aimed to investigate the neuroprotective effect of TXL on focal cerebral ischemia and reperfusion injury in rats by attenuating its brain damage and neuronal apoptosis, and to assess the potential role of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in this protection. MATERIALS AND METHODS: Adult Male Sprague-Dawley rats (n=120) were randomly divided into 5 groups: sham, cerebral ischemia and reperfusion (I/R), cerebral ischemia and reperfusion plus TXL (1.6g/kg/day) (TXL1.6), TXL1.6 plus LY294002 and dimethyl sulfoxide (DMSO) (TXL1.6+LY294002), TXL1.6 plus DMSO (TXL1.6+vehicle). Prior to the grouping, TXL1.6 was selected to be the optimal dose of TXL by evaluating the neurological deficits score of five group rats (Sham, I/R, TXL0.4, TXL0.8 and TXL1.6, n=30) at 0, 1, 3, 5, and 7 days after reperfusion. Rats, being subjected to middle cerebral artery occlusion (MCAO) for 90min followed by 24h reperfusion, were the cerebral ischemia/reperfusion models. At 24h after reperfusion, cerebral infarct area was measured via tetrazolium staining and neuronal damage was showed by Nissl staining. The double staining of Terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL) staining and immunofluorescence labeling with NeuN, was performed to evaluate neuronal apoptosis. Proteins involved in PI3K/Akt pathway were detected by Western blot. RESULTS: The results showed that TXL markedly improved neurological function, reduced cerebral infarct area, decreased neuronal damage, and significantly attenuated neuronal apoptosis, while these effects were eliminated by inhibition of PI3K/Akt with LY294002. We also found that TXL up regulated the expression levels of p-PDK1, p-Akt, p-c-Raf, p-BAD and down regulated Cleaved caspase 3 expression notably, which were partially reversed by LY294002. Additionally, the increment of p-PTEN level on which LY294002 had little effect was also detected in response to TXL treatment. CONCLUSIONS: These findings demonstrated that TXL provided neuroprotection against cerebral ischemia/reperfusion injury and neuronal apoptosis, and this effect was mediated partly by activation of the PI3K/Akt pathway. PMID- 26805464 TI - Hyperpolarization-activated cation and T-type calcium ion channel expression in porcine and human renal pacemaker tissues. AB - Renal pacemaker activity triggers peristaltic upper urinary tract contractions that propel waste from the kidney to the bladder, a process prone to congenital defects that are the leading cause of pediatric kidney failure. Recently, studies have discovered that hyperpolarization-activated cation (HCN) and T-type calcium (TTC) channel conductances underlie murine renal pacemaker activity, setting the origin and frequency and coordinating upper urinary tract peristalsis. Here, we determined whether this ion channel expression is conserved in the porcine and human urinary tracts, which share a distinct multicalyceal anatomy with multiple pacemaker sites. Double chromagenic immunohistochemistry revealed that HCN isoform 3 is highly expressed at the porcine minor calyces, the renal pacemaker tissues, whereas the kidney and urinary tract smooth muscle lacked this HCN expression. Immunofluorescent staining demonstrated that HCN(+) cells are integrated within the porcine calyx smooth muscle, and that they co-express TTC channel isoform Cav3.2. In humans, the anatomic structure of the minor calyx pacemaker was assayed via hematoxylin and eosin analyses, and enabled the visualization of the calyx smooth muscle surrounding adjacent papillae. Strikingly, immunofluorescence revealed that HCN3(+) /Cav3.2(+) cells are also localized to the human minor calyx smooth muscle. Collectively, these data have elucidated a conserved molecular signature of HCN and TTC channel expression in porcine and human calyx pacemaker tissues. These findings provide evidence for the mechanisms that can drive renal pacemaker activity in the multi-calyceal urinary tract, and potential causes of obstructive uropathies. PMID- 26805467 TI - Regulation of drug-metabolizing enzymes and efflux transporters by Astragali radix decoction and its main bioactive compounds: Implication for clinical drug drug interactions. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Astragali radix ("Huang Qi" in Chinese, HQ) is a well-known traditional Chinese herbal medicine that possesses various biological functions. Astragaloside IV (AS-IV), calycosin (CS), and formononetin (FMNT) are the three main bioactive compounds of HQ that are responsible for its pharmacological activities and therapeutic efficacy. AIM OF THE STUDY: This study aims to investigate the effects of HQ, AS-IV, CS, and FMNT on major human drug metabolizing enzymes (DMEs), including CYP3A4, CYP2B6, CYP2E1, UGT1A, UGT1A6, SULT1A1, and SULT1A3, as well as efflux transporters (ETs), including P-gp, MRP2, BCRP, MRP1, and MRP3, by using HepG2 cell line. Results would provide beneficial information for the proper clinical application of HQ. MATERIALS AND METHODS: HepG2 cells were treated with HQ, AS-IV, CS, and FMNT for 96h. Cell viability was examined by MTT assay. The protein and mRNA levels of DMEs and ETs were measured using Western blot and real-time PCR, respectively. RESULTS: Compared with the control group, HQ considerably increased the expression levels of CYP3A4, CYP2B6, CYP2E1, UGT1A, P-gp, MRP2, BCRP, and MRP3 in a dose-dependent manner. Inversely, HQ significantly decreased the protein levels of UGT1A6, SULT1A1, and MRP1. Exposure to AS-IV induced the protein levels of UGT1A, P-gp, MRP1, and MRP3, but produced inhibitory effects on CYP3A4, CYP2B6, and BCRP. The expression levels of CYP3A4, UGT1A, SULT1A1, P-gp, MRP2, and MRP3 were remarkably increased in the CS treated cells, whereas the protein levels of SULT1A3 and BCRP were decreased. FMNT treatment induced the protein levels towards CYP3A4, CYP2B6, UGT1A, P-gp, MRP1, MRP2, and MRP3, but inhibited the expression of CYP2E1, SULT1A1, and SULT1A3. CONCLUSIONS: HQ and its main bioactive compounds, including AS-IV, CS, and FMNT significantly regulated the expression of the major DMEs and ETs. HQ produced stronger regulations (induction or inhibition) on DMEs and ETs than AS IV, CS, or FMNT alone. The results indicate that potential drug-drug interactions might exist when the tested drugs, specifically HQ, are co-administered with other substrate drugs that are metabolized or transported via the studied DMEs or ETs. This study provides beneficial information for appropriate use of HQ for clinical therapy. PMID- 26805468 TI - Tongxinluo reduces brain edema and inhibits post-ischemic inflammation after middle cerebral artery occlusion in rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo (TXL), a widely used traditional Chinese medicine, has been proved multiple therapeutic effects in cerebral ischemic infraction. The purpose of this study was to investigate the protective effects of TXL on the brain edema and post-ischemic inflammatory response. MATERIALS AND METHODS: Middle cerebral artery occlusion in the rat was used as the ischemia model. Rats were treated with TXL. In the first stage, the best dosage was chosen based on functional assessment and infarct size. In the second stage, rats were randomly divided into 5 groups: sham control (sham), ischemia and reperfusion (IR) 24h, TXL24h, I/R72h, TXL72h. TXL(1.6g/kg/day) administration was pre-performed for 3 days in TXL groups, and was post-performed for 24h (TXL24h group) or 72h (TXL72h group). Brain edema was measured by water content, MRI and AQP4 expression. Iba1, HMGB1, TLR4, NF-kappaB expression were examined by immunofluorescence staining or Western blot. TNF-alpha was determined by enzyme linked immunosorbent assay. RESULTS: High dose (1.6g/kg/day) of TXL remarkably reduced neurological deficit scores and cerebral infarct area. Compared with those results of I/R24h group, pre-post treatment with TXL for 3 days decreased brain water content, down-regulated AQP4 expression, lowered relative signal intensity of T2WI, reduced lesion volume ratio, and inhibited the activation of microglia, HMGB1, TLR4, NF-kappaB and TNF-alpha. CONCLUSIONS: These results indicated that the TXL pre-post treatment for 3 days could be an effective therapy for brain ischemia by inhibiting the development of brain edema and post ischemic inflammation. PMID- 26805469 TI - Extraction and characterization of triglycerides from coffeeweed and switchgrass seeds as potential feedstocks for biodiesel production. AB - BACKGROUND: Although switchgrass has been developed as a biofuel feedstock and its potential for bioethanol and bio-oil from fast pyrolysis reported in the literature, the use of the seeds of switchgrass as a source of triglycerides for biodiesel production has not been reported. Similarly, the potential for extracting triglycerides from coffeeweed (an invasive plant of no current economic value) needs to be investigated to ascertain its potential economic use for biodiesel production. RESULTS: The results show that coffeeweed and switchgrass seeds contain known triglycerides which are 983 and 1000 g kg(-1) respectively of the fatty acids found in edible vegetable oils such as sunflower, corn and soybean oils. In addition, the triglyceride yields of 53-67 g kg(-1) of the seed samples are in the range of commercial oil-producing seeds such as corn (42 g kg(-1) ). CONCLUSION: The results also indicate that the two non-edible oils could be used as substitutes for edible oil for biodiesel production. In addition, the use of seeds of switchgrass for non-edible oil production (as a feedstock for the production of biodiesel) further increases the total biofuel yield when switchgrass is cultivated for use as energy feedstock for pyrolysis oil and biodiesel production. (c) 2016 Society of Chemical Industry. PMID- 26805471 TI - Species composition, co-occurrence, association and affinity indices of mosquito larvae (Diptera: Culicidae) in Mazandaran Province, northern Iran. AB - Although considerable progress has been made in the past years in management of mosquito borne diseases such as malaria, dengue, yellow fever and West Nile fever through research in biology and ecology of the vectors, these diseases are still major threats to human health. Therefore, more research is required for better management of the diseases. This investigation provides information on the composition, co-occurrence, association and affinity indices of mosquito larvae in Mazandaran Province, northern Iran. In a large scale field study, mosquito larvae were collected from 120 sentinel sites in 16 counties in Mazandaran Province, using standard 350 ml dipper. Sampling took place monthly from May to December 2014. Collected larvae were mounted on glass slides using de Faure's medium and were diagnosed using morphological characters. Totally, 19,840 larvae were collected including three genera and 16 species from 120 larval habitats, as follows: Anopheles claviger, Anopheles hyrcanus, Anopheles maculipennis s.l., Anopheles marteri, Anopheles plumbeus, Anopheles pseudopictus, Culex pipiens, Culex tritaeniorhynchus, Culex torrentium, Culex perexiguus, Culex territans, Culex mimeticus, Culex hortensis, Culiseta annulata, Culiseta longiareolata, and Culiseta morsitans. Predominant species were Cx. pipiens and An. maculipennis s.l. which show the highest co-occurrence. The pair of species An. hyrcanus/An. pseudopictus showed significant affinity and association. High co-occurrence of the predominant species Cx. pipiens and An. maculipennis s.l. in the study area is of considerable importance in terms of vector ecology. It was also revealed that An. pseudopictus/An. hyrcanus often occur sympatrically indicating their common habitat requirements. The information may be equally important when vector control measures are considered. PMID- 26805474 TI - DIMENSIONS OF PRIVACY PREFERENCES. AB - The development of the Privacy Preference Scale, a 56 item five-choice summative scale, is described. Six subscales were constructed from a principal axis factor analysis with unities in the diagonal of an 86 item pool; these focused on preferences for non-involvement with neighbors, seclusion of the home, solitude, privacy with intimates, anonymity, and reserve. The ability of the subscales to differentiate between age and sex groups, and their relationship to personality measures (the Myers-Briggs Type Indicator) and to self-reported privacy oriented behavior are presented. PMID- 26805472 TI - A systematic review of the role of re-laparoscopy in the management of complications following laparoscopic colorectal surgery. AB - The benefits of laparoscopic versus open surgery for patients with both benign and malignant colorectal disease have been well established. Re-laparoscopy in patients who develop complications following laparoscopic colorectal surgery has recently been reported by some groups and the aim of this systematic review was to summarise this literature. A literature search of PubMed, Medline and EMBASE identified a total of 11 studies that reported laparoscopic re-intervention for complications in 187 patients following laparoscopic colorectal surgery. The majority of these patients required re-intervention in the immediate postoperative period (i.e. less than seven days). Anastomotic leakage was the commonest complication requiring re-laparoscopy reported (n = 139). Other complications included postoperative hernia (n = 12), bleeding (n = 9), adhesions (n = 7), small bowel obstruction (n = 4), colonic ischaemia (n = 4), bowel and ureteric injury (n = 3 respectively) and colocutaneous fistula (n = 1). Ninety seven percent of patients (n = 182) who underwent re-laparoscopy had their complications successfully managed by re-laparoscopy, maintaining the benefits of the laparoscopic approach and avoiding a laparotomy. We conclude that re laparoscopy for managing complications following laparoscopic colorectal surgery appears to be safe and effective in highly selected patients. PMID- 26805473 TI - The management of osteomyelitis in the adult. AB - BACKGROUND AND PURPOSE: Osteomyelitis (OM) is considered one of the most challenging medical conditions an orthopaedic surgeon has to face. Much debate is present concerning diagnosis and treatment, especially about differences between acute and chronic forms of the condition. The main aim of the present work is to show the key points where research should be implemented. METHODS: Online database were searched to find evidence about the clinical management of osteomyelitis. Clinical randomized trials, case series, prospective cohort studies reporting on diagnosis and treatment of acute and chronic osteomyelitis were taken into consideration. Cadaveric studies, laboratory studies, case reports, review articles and meta-analyses were excluded. Furthermore, studies concerning implant related OM were excluded. Studies in English, Spanish and French were considered in this process of inclusion. The cohorts of all the included studies were composed of adult patients. RESULTS: The main growpoints concerning OM are the identification of a correct laboratory test array to allow a prompt diagnosis and provide a sensitive and specific detection of the bacterial species involved, along with antibiotic drug resistance; optimal imaging techniques, according to the phase of the infection, have to be performed, to avoid unnecessary medical expenses; the identification of a suitable compromise between intravenous and oral drugs administration. A flow chart is proposed for optimal clinical management of this pathology. CONCLUSION: More work should be carried out to clarify the main issues concerning the clinical management of osteomyelitis in adult patients. PMID- 26805476 TI - "SOMETIMES, IT'S OKAY TO FACTOR DIFFERENCE SCORES"-THE SEPARATION OF STATE AND TRAIT ANXIETY. AB - Contemporary psychometric policy and practice have tended to make the use of algebraic difference scores in psychological research taboo. Within the more limited domain of factor analytic research on personality, difference scores have been the subject of sporadic debate for more than 30 years. Using the personality trait versus state distinction as a substantive context, the fit of the factor analytic model to difference score data is investigated and found to be quite good. Methodological issues related to properties of difference scores and their implications for personality research are briefly discussed. PMID- 26805477 TI - FACTOR STRUCTURE O F THE MMPI IN A PSYCHIATRIC POPULATION. AB - A multi-stage factor analysis of the 373-item short form of the MMPI revealed six factors consistent with item-level analyses of a number of other investigators and with those previously identified by the authors in analysis of the first 168 items: (1) Somatization, (2) Feminine Interests, (3) Depression, (4) Psychotic Distortion, (5) Low Morale, and ( 6 ) Acting Out. Scoring keys for the six factors are presented along with 2'-score profile sheets and T-score equivalents of raw factor scores derived from a normal college population with clinical profiles comparable to those reported for other college groups. Factor scoring, with its more homogeneous content, promises to simplify pattern interpretation insofar as the more common code types tend to be represented in single factors. Moreover, since the MMPI-168 shows a factor structure consistent with the longer form, it seems justified to use it in situations requiring an abbreviated administration. PMID- 26805478 TI - TESTING THE NULL HYPOTHESIS FOR ROTATION TO A TARGET. AB - This study proposes and illustrates a method for estimating the degree to which a factor rotation to an hypothesized target represents an improvement over rotation to a random target. The original hypothesized target matrix is transformed so that the direction of targeted salients is randomly determined with the restriction that the new target is orthogonal to the original. When applied to a factor matrix of content and response style measures, the hypothesized target yielded a decidedly better fit to the data than did the random target. PMID- 26805479 TI - THE STRUCTURE OF ATTITUDE TOWARD QUANTITATIVE CONCEPTS. AB - The purpose of this study was to assess the dimensionality of attitude toward quantitative concepts. Subjects were 311 graduate students. The instrument employed was a semantic differential consisting of six quantitative concepts and 14 evaluative scales. The concepts were: Algebra, Statistics, Mathematics, Numbers, Calculations, and Formulas. An obliquely rotated principal factor analysis of the data yielded two categories of interpretable factors: (1) factors defined by all scales within one quantitative concept, and (2) factors defined by a sub-set of scales across quantitative concepts. PMID- 26805480 TI - CLUSTER ANALYSIS OF PERSONAL ORIENTATION INVENTORY ITEMS IN A PRISON SAMPLE. AB - The responses of 500 male prisoners to the 150 items of the Personal Orientation Inventory (POI) were clustered, using elementary linkage analysis. Five major clusters accounted for 74 of the 150 items in the POI. K-R 20 reliabilities of these clusters compared quite favorably with those of the original scales, but scale scores could be predicted with only fair accuracy from cluster scores. The invariance of the present solution and the relative validity of cluster scores and scale scores remain to be determined. PMID- 26805481 TI - THE DETERMINATION OF THE UNDERLYING DIMENSIONALITY OF AN EMPIRICALLY OBTAINED MATRIX OF PROXIMITIES. AB - A completely automatic procedure for determining the underlying dimensionality of an empirically obtained matrix of proximities is described. This technique is based on the results of an extensive Monte Carlo experiment and may be applied to matrices of order 12 to 36 inclusive. A computer program which will implement the procedure is available from the authors. PMID- 26805482 TI - COMMENTS ON THE STONE-COLES MULTIDIMENSIONAL SCALING METHOD. AB - It is shown that the Stone-Coles method is not a content method, but rather an alternative to the ordinary distance methods. As such, it is argued, it is of limited value. PMID- 26805483 TI - A GENERALIZATION OF VECTOR CORRELATION AND ITS RELATION TO CANONICAL CORRELATION. AB - Chow (1966) has shown that the least-squares estimate of the regression coefficient matrix in multivariate linear regression maximizes the squared vector correlation coefficient between the dependent variables and a linear transformation of the independent variables. This paper shows that the problem is closely related to canonical correlation, and that the correlation involved is the product of the canonical correlations between the independent and dependent variables. The paper gives a symmetric generalization of vector correlation which applies to matrices with different numbers of variables and with linear dependencies among the variables. It is shown to be also related to canonical correlation, as well as to a measure of correlation between sets of variables proposed by Rozeboom (1965). This provides a test of significance for both measures and suggests that the vector correlation may be used as a measure of linear relationship between sets of variables. PMID- 26805484 TI - ANALYSIS OF REPEATED MEASURES AND OTHER DESIGNS. AB - For small and balanced analysis of variance problems, standard computer programs are convenient and efficient. For large problems, regression pro- grams are at least competitive with analysis of variance programs; and, when a problem is unbalanced, they usually provide the only reasonable solution. This paper discusses procedures for using regression programs for the computing of analyses of variance. A procedure for coding matrices is described for experimental designs having nested and crossed factors. Several illustrations are given, and the limitation of the procedure with large repeated measures designs is discussed. A second algorithm is offered for obtaining the sums of squares for nested factors and their interactions in such designs. PMID- 26805485 TI - A COMPARISON OF THE CLASSIFICATION ACCURACY OF PROFILE SIMILARITY MEASURES. AB - Thirteen profile similarity measures were compared, using generated data. Profiles were generated from sets of three standards by adding random and normally distributed error components to the profile points of the standards. The three standards within each set were vaned systematically, altering the elevation, scatter, and shape similarities between the standards. A correct classification occurred if the generated profile was most similar to the standard from which it was generated. Significant differences were found between the proportions of correct classifications for the 13 profile similarity measures under all conditions. Osgood and Suci's D and Cattell's rB were superior to or equal to all other measures under all conditions. PMID- 26805487 TI - Direct difunctionalization of activated alkynes via domino oxidative benzylation/1,4-aryl migration/decarboxylation reactions under metal-free conditions. AB - The oxidative difunctionalization of aryl alkynoates via benzyl radical initiated intramolecular 1,4-aryl migration and decarboxylation tandem process was developed in the presence of tert-butyl hydroperoxide as an oxidant, which provides a direct and selective route to a variety of trisubstituted alkenes from simple toluene derivatives and aryl alkynoates. PMID- 26805488 TI - The occurrence of delayed ocular hypertension and glaucoma after pars plana vitrectomy for rhegmatogenous retinal detachment. PMID- 26805489 TI - Actinomycetes inhibit filamentous fungi from the cuticle of Acromyrmex leafcutter ants. AB - Actinomycetes bacteria associated with leafcutter ants produce secondary metabolites with antimicrobial properties against Escovopsis, a fungus specialized in attacking the gardens of fungus-growing ants, which denies the ants their food source. Because previous studies have used fungi isolated from fungus gardens but not from ant integument, the aims of the present study were to isolate actinomycetes associated with the cuticle of the Acromyrmex spp. and to quantify their inhibition abilities against the filamentous fungal species carried by these ants. The results demonstrated that actinomycetes had varied strain-dependent effects on several filamentous fungal species in addition to antagonistic activity against Escovopsis. The strain isolated from Acromyrmex balzani was identified as a Streptomyces species, whereas the remaining isolates were identified as different strains belonging to the genus Pseudonocardia. These findings corroborate the hypothesis that actinomycetes do not act specifically against Escovopsis mycoparasites and may have the ability to inhibit other species of pathogenic fungi. PMID- 26805492 TI - [Properties of the Measures to Assess Oxaliplatin-induced Peripheral Neuropathy: A Literature Review]. AB - PURPOSE: The purpose of this study is to provide a comprehensive overview of the various measures available for assessment of oxaliplatin-induced peripheral neuropathy (OXLIPN) and to evaluate the measurement properties of each assessment tool. METHODS: A systematic review was conducted to identify existing measures for OXLIPN found in the databases of PubMed, Cochrane Library, Embase, RISS and KoreaMed. The quality of the 24 identified tools was evaluated based on their properties of measurement including content validity, internal consistency, criterion validity, construct validity, reproducibility, responsiveness, floor ceiling effects and interpretability. RESULTS: Ten (41.7%) of the 24 tools were identified as specific measures for assessing OXLIPN and the most popular type of measures were clinical grading systems by clinicians (58.3%) and only 29.2% of measures were identified as patient reported outcomes. The most frequently used tool was National Cancer Institute-Common Toxicity Criteria (NCI-CTC), but the validity of NCI-CTC has not been reported appropriately. Overall, the Neuropathic Pain Symptom Inventory (NPSI) received the best psychometric scores, and the Chemotherapy-induced Peripheral Neuropathy Assessment Tool (CIPNAT) and Functional Assessment of Cancer Therapy/Gynaecologic Oncology Group-neurotoxicity 12 (FACT/GOG-Ntx-12) followed NPSI. CONCLUSION: To select appropriate measure, evidences should be accumulated through the clinical use of tools. Therefore, practitioner and researchers are urged to report relevant statistics required for the validation of the currently used measures for assessment of OXLIPN. PMID- 26805490 TI - Mesenchymal stem cells maintain their defining stem cell characteristics after treatment with cisplatin. AB - Mesenchymal stem cells (MSCs) aid the regeneration of tissues damaged by treatment with cisplatin. However, the effects of this cytotoxic drug on the stem cells have been largely unknown. Here we demonstrate that human bone marrow derived MSCs are relatively resistant to cisplatin treatment and show resistance levels comparable to these of differentiated fibroblasts. Cisplatin did not affect cellular morphology, adhesion or induction of apoptosis in MSCs. The potential for differentiation was preserved after exposure to cisplatin, and established MSC surface markers were observed to be stably expressed irrespective of cisplatin treatment. Cytoskeletal rearrangements and high expression levels of individual heat shock proteins were detected in MSCs and may be partly responsible for the observed cisplatin resistance. The cisplatin-resistant phenotype of human MSCs supports the concept of further investigating these stem cells as a potential treatment option for cisplatin-induced tissue damage. PMID- 26805493 TI - [Structural Equation Modeling on Living and Brain Death Organ Donation Intention in Nursing Students]. AB - PURPOSE: The purpose of this study was to test and validate a model to predict living and brain death organ donation intention in nursing students. The conceptual model was based on the theory planned behavior. METHODS: Quota sampling methodology was used to recruit 921 nursing students from all over the country and data collection was done from October 1 to December 20, 2013. RESULTS: The model fit indices for the hypothetical model were suitable for the recommended level. Knowledge, attitude, subjective norm and perceived behavioral control explained 40.2% and 40.1% respectively for both living and brain death organ donation intention. Subjective norm was the most direct influential factor for organ donation intention. Knowledge had significant direct effect on attitude and indirect effect on subjective norm and perceived behavioral control. These effects were higher in brain death organ donation intention than in living donation intention. CONCLUSION: The overall findings of this study suggest the need to develop systematic education programs to increases knowledge about brain death organ donation. The development, application, and evaluation of intervention programs are required to improve subjective norm. PMID- 26805494 TI - [Effects of Lifestyle Intervention on Fatigue, Nutritional Status and Quality of Life in Patients with Gynecologic Cancer]. AB - PURPOSE: The purpose of this study was to examine the effect of lifestyle intervention on the development of fatigue, nutritional status and quality of life of patients with gynecologic cancer. METHODS: A nonequivalent control group quasi-experimental design was used. Participants were 49 patients with gynecologic cancer. They were assigned to the experiment group (n=24) or the control group (n=25). The lifestyle intervention for this study consisted of physical activity, nutritional education, telephone call counseling, health counseling, monitoring for lifestyle, and affective support based on Cox's Interaction Model of Client Health Behavior and was implemented for six weeks. RESULTS: Significant group differences were found for fatigue (p =.037), nutritional status (p =.034) and social/family well-being (p =.035) in these patients with gynecologic cancer. CONCLUSION: Results indicate that this lifestyle intervention is effective in lessening fatigue, and improving nutritional status and social/family well-being. Therefore, nurses in hospitals should develop strategies to expand and provide lifestyle interventions for patients with cancer. PMID- 26805495 TI - [Effects of a Thera-Band Exercise Program on Pain, Knee Flexion ROM, and Psychological Parameters Following Total Knee Arthroplasty]. AB - PURPOSE: The purpose of the study was to investigate the effects of the Thera Band exercise program following total knee arthroplasty. METHODS: The research design for this study was a nonequivalent control group non-synchronized design. Participants were 30 patients for the experimental group and 30 patients for the control group. The experimental group participated in the Thera- Band exercise program in addition to conventional CPM (continuous passive motion) exercise. The control group received conventional CPM exercise only. Outcome measures were pain, knee flexion range of motion, CRP, and psychological parameters (self efficacy and fear of falling). Data were analyzed using chi2-test, Fisher's exact test, t-test, and repeated measure ANOVA with SPSS/PC version 21.0. RESULTS: There were significant improvement in self-efficacy, and decreases in pain, and fear of falling in the experimental group compared to the control group. However, no significant differences were found between the two groups for CRP and knee flexion ROM. CONCLUSION: The Thera-Band exercise program gave an additional benefit over the conventional CPM exercise for patients following total knee arthroplasty, and is recommended for use as an effective nursing intervention for patients after total knee arthroplasty. PMID- 26805496 TI - [Development of Empowerment Program for Persons with Chronic Mental Illness and Evaluation of Impact]. AB - PURPOSE: This study was done to develop an empowerment program for people with chronic mental illness and to analyze effects of the program on level of empowerment. METHODS: The research was conducted using a nonequivalent control group pretest-posttest design. Participants were 37 people with chronic mental illness (experimental group: 18, control group: 19). The empowerment program was provided for 8 weeks (15 sessions). Data were collected between July 21 and October 17, 2014. Data were analyzed using Chi-square, Fisher's exact test, Sapiro-Wilk test, and Repeated measure ANOVA with SPSS/WIN 18.0. RESULTS: Quantitative results show that self-efficacy, interpersonal relationships, attitudes in the workplace, occupational performance capacity, and levels of empowered execute were significantly better in the experimental group compared to the control group. CONCLUSION: Study findings indicate that this empowerment program for persons with chronic mental illness is effective for improving self efficacy, interpersonal skills, attitudes in the workplace, occupational performance capacity, levels of empowered execute. PMID- 26805497 TI - [Symptom Management to Predict Quality of Life in Patients with Heart Failure: A Structural Equation Modeling Approach]. AB - PURPOSE: The focus of this study was on symptom management to predict quality of life among individuals with heart failure. The theoretical model was constructed based on situation-specific theory of heart failure self-care and literature review. METHODS: For participants, 241 outpatients at a university hospital were invited to the study from May 19 to July 30, 2014. Data were collected with structured questionnaires and analyzed using SPSSWIN and AMOS 20.0. RESULTS: The goodness of fit index for the hypothetical model was .93, incremental fit index, .90, and comparative fit index, .90. As the outcomes satisfied the recommended level, the hypothetical model appeared to fit the data. Seven of the eight hypotheses selected for the hypothetical model were statistically significant. The predictors of symptom management, symptom management confidence and social support together explained 32% of the variance in quality of life. The 28% of variance in symptom management was explained by symptom recognition, heart failure knowledge and symptom management confidence. The 4% of variance in symptom management confidence was explained by social support. CONCLUSION: The hypothetical model of this study was confirmed to be adequate in explaining and predicting quality of life among patients with heart failure through symptom management. Effective strategies to improve quality of life among patients with heart failure should focus on symptom management. Symptom management can be enhanced by providing educational programs, encouraging social support and confidence, consequently improving quality of life among this population. PMID- 26805498 TI - [Ecological Correlates of Cardiovascular Disease Risk in Korean Blue-collar Workers: A Multi-level Study]. AB - PURPOSE: The purpose of this study was to investigate individual and organizational level of cardiovascular disease (CVD) risk factors associated with CVD risk in Korean blue-collar workers working in small sized companies. METHODS: Self-report questionnaires and blood sampling for lipid and glucose were collected from 492 workers in 31 small sized companies in Korea. Multilevel modeling was conducted to estimate effects of related factors at the individual and organizational level. RESULTS: Multilevel regression analysis showed that workers in the workplace having a cafeteria had 1.81 times higher CVD risk after adjusting for factors at the individual level (p=.022). The explanatory power of variables related to organizational level variances in CVD risk was 17.1%. CONCLUSION: The results of this study indicate that differences in the CVD risk were related to organizational factors. It is necessary to consider not only individual factors but also organizational factors when planning a CVD risk reduction program. The factors caused by having cafeteria in the workplace can be reduced by improvement in the CVD-related risk environment, therefore an organizational-level intervention approach should be available to reduce CVD risk of workers in small sized companies in Korea. PMID- 26805499 TI - [The Psychosocial Adaptation Process of Psychiatric Nurses Working in Community Mental Health Centers]. AB - PURPOSE: The aim of this study was to verify psychosocial issues faced by psychiatric and community mental health nurse practitioners (PCMHNP) working in community mental health centers, and to identify the adaptation processes used to resolve the issues. METHODS: Data were collected through in-depth interviews between December 2013 and August 2014. Participants were 11 PCMHNP working in community mental health centers. Analysis was done using the grounded theory methodology. The first question was "How did you start working at a community mental health center; what were the difficulties you faced during your employment and how did you resolve them?" RESULTS: The core category was 'regulating within relationships.' The adaptation process was categorized into three sequential stages: 'nesting,' 'hanging around the nest,' and 'settling into the nest.' Various action/interaction strategies were employed in these stages. The adaptation results from using these strategies were 'psychiatric nursing within life' and 'a long way to go.' CONCLUSION: The results of this study are significant as they aid in understanding the psychosocial adaptation processes of PCMHNP working in community mental health centers, and indicate areas to be addressed in the future in order for PCMHNP to fulfill their professional role in the local community. PMID- 26805500 TI - [Structural Equation Modeling of Quality of Work Life in Clinical Nurses based on the Culture-Work-Health Model]. AB - PURPOSE: The purpose of this study was to construct and test a structural equation model of quality of work life for clinical nurses based on Peterson and Wilson's Culture-Work-Health model (CWHM). METHODS: A structured questionnaire was completed by 523 clinical nurses to analyze the relationships between concepts of CWHM-organizational culture, social support, employee health, organizational health, and quality of work life. Among these conceptual variables of CWHM, employee health was measured by perceived health status, and organizational health was measured by presenteeism. SPSS21.0 and AMOS 21.0 programs were used to analyze the efficiency of the hypothesized model and calculate the direct and indirect effects of factors affecting quality of work life among clinical nurses. RESULTS: The goodness-of-fit statistics of the final modified hypothetical model are as follows: chi2=586.03, chi2/df=4.19, GFI=.89, AGFI=.85, CFI=.91, TLI=.90, NFI=.89, and RMSEA=.08. The results revealed that organizational culture, social support, organizational health, and employee health accounted for 69% of clinical nurses' quality of work life. CONCLUSION: The major findings of this study indicate that it is essential to create a positive organizational culture and provide adequate organizational support to maintain a balance between the health of clinical nurses and the organization. Further repeated and expanded studies are needed to explore the multidimensional aspects of clinical nurses' quality of work life in Korea, including various factors, such as work environment, work stress, and burnout. PMID- 26805501 TI - [Factors Influencing Posttraumatic Growth in Fathers of Chronically ill Children]. AB - PURPOSE: The purpose of this study was to identify the level of distress and posttraumatic growth in fathers of chronically ill children and also, to identify the relation between characteristics of the fathers and children and their posttraumatic growth and to investigate factors that influence posttraumatic growth. METHODS: In this study, 48 fathers who visited a university hospital in Seoul, Korea and who gave written consent completed the questionnaire between September 23 and November 19, 2013. Data were analyzed using Mann-Whitney U test, Kruskal-Wallis test, Pearson correlation coefficient and stepwise multiple regression. RESULTS: The level of distress in fathers of chronically ill children was relatively high and the majority of them were experiencing posttraumatic growth. Models including the variable (deliberate rumination, religiousness, optimism) explained 64.3% (F=26.38, p<.001) of the variance for posttraumatic growth. Deliberate rumination (beta=.59, p<.001) was the most influential factor. CONCLUSION: The findings demonstrate that it is essential for nurses to intervene and facilitate continuously so as to promote posttraumatic growth and relieve distress in fathers of chronically ill children. Furthermore, it is also necessary for nurses to find ways to develop ideal interventions to activate deliberate rumination and offer spiritual care and help maintain optimism in these individuals. PMID- 26805502 TI - [A Structural Equation Model on Family Strength of Married Working Women]. AB - PURPOSE: The purpose of this study was to identify the effect of predictive factors related to family strength and develop a structural equation model that explains family strength among married working women. METHODS: A hypothesized model was developed based on literature reviews and predictors of family strength by Yoo. This constructed model was built of an eight pathway form. Two exogenous variables included in this model were ego-resilience and family support. Three endogenous variables included in this model were functional couple communication, family stress and family strength. Data were collected using a self-report questionnaire from 319 married working women who were 30~40 of age and lived in cities of Chungnam province in Korea. Data were analyzed with PASW/WIN 18.0 and AMOS 18.0 programs. RESULTS: Family support had a positive direct, indirect and total effect on family strength. Family stress had a negative direct, indirect and total effect on family strength. Functional couple communication had a positive direct and total effect on family strength. These predictive variables of family strength explained 61.8% of model. CONCLUSION: The results of the study show a structural equation model for family strength of married working women and that predicting factors for family strength are family support, family stress, and functional couple communication. To improve family strength of married working women, the results of this study suggest nursing access and mediative programs to improve family support and functional couple communication, and reduce family stress. PMID- 26805503 TI - Application and Developmental Strategies for Community-Based Injury Prevention Programs of the International Safe Communities Movement in Korea. AB - PURPOSE: Safety of humans is an important factor that affects health overall, and injuries are one of the major public-health problems in the world. The purposes of this study were to describe the International safe Community movement which contributes to the injury prevention and safety promotion all over the world, and to identify out the application and developmental strategies for Korea. METHODS: A review was done of previous research, reviews, and reports on the history, concepts, basic principles, and recommendations for actions of the Safe Community. RESULTS: For this study, the application strategies of the International Safe Community movement in Korea were examined to deduce the strengths of the safe Community program. Community-based injury prevention work according to the International Safe Community model is a successful and cost effective way of reducing injuries in the community. CONCLUSION: Through the International Safe Community program, communities are able to realize a healthy community and achieve improved quality of lives for the people, which is the ultimate objective of the Safe Community model. In addition, it will contribute to the economic vitalization and gain through energy and enhancement of productivity of people. PMID- 26805504 TI - Transitional Care for Older Adults with Chronic Illnesses as a Vulnerable Population: Theoretical Framework and Future Directions in Nursing. AB - PURPOSE: Effective transitional care is needed to improve the quality of life in older adult patients with chronic illness and avoid discontinuity of care and adverse events. The aim of this article is to provide an overview of the key features, broader implications, and the utility of Meleis' transition theory intended for the transitional care of older adults with chronic illnesses. We present the role of nurse in the context of transitional care and propose future directions to increase the quality of nursing care. METHODS: The online databases Cumulative Index of Nursing and Allied Health Literature, MEDLINE, and Science Direct were searched for relevant literature published since 1970 along with textbooks regarding nursing theory. RESULTS: An evaluation of the usefulness of transition theory based on transitional care in older adult patients with chronic illnesses is provided. Healthy transition should be the expected standard of nursing care for older adults across all healthcare settings. CONCLUSION: Nurses need to contribute to the development of transitional care for vulnerable populations; however, transition theory needs to be enhanced through additional theoretical work and repeated evaluations of the applicability in areas of transitional care. PMID- 26805505 TI - Effects of Neurofeekback Training on EEG, Continuous Performance Task (CPT), and ADHD Symptoms in ADHD-prone College Students. AB - PURPOSE: This study explored the effects of neurofeedback training on Electroencephalogram (EEG), Continuous Performance Task (CPT) and ADHD symptoms in ADHD prone college students. METHODS: Two hundred forty seven college students completed Korean Version of Conners' Adult ADHD Rating Scales (CAARS-K) and Korean Version of Beck Depression Inventory (K-BDI). The 16 participants who ranked in the top 25% of CAARS-K score and had 16 less of K-BDI score participated in this study. Among them, 8 participants who are fit for the research schedule were assigned to neurofeedback training group and 8 not fit for the research schedule to the control group. All participants completed Adult Attention Deficiency Questionnaire, CPT and EEG measurement at pretest. The neurofeedback group received 15 neurofeedback training sessions (5 weeks, 3 sessions per week). The control group did not receive any treatment. Four weeks after completion of the program, all participants completed CAARS-K, Adult Attention Deficiency Questionnaire, CPT and EEG measurement for post-test. RESULTS: The neurofeedback group showed more significant improvement in EEG, CPT performance and ADHD symptoms than the control group. The improvements were maintained at follow up. CONCLUSION: Neurofeedback training adjusted abnormal EEG and was effective in improving objective and subjective ADHD symptoms in ADHD prone college students. PMID- 26805506 TI - Applying the Flipped Learning Model to an English-Medium Nursing Course. AB - PURPOSE: An emerging trend in Asian higher education is English-medium instruction (EMI), which uses English as the primary instructional language. EMI prepares domestic students for international leadership; however, students report difficulty in learning, and educators have raised questions concerning the effectiveness of EMI. The flipped learning model (FLM), in which lecture and homework activities for a course are reversed, was applied to an English-medium course offered by a college of nursing in Korea. The aims of this study were to: 1) revise an existing English-medium nursing course using the FLM; 2) explore students' learning experiences and their acceptance of the FLM; and 3) identify key factors in the success of FLM. METHODS: We used a descriptive, cross sectional, mixed-methods design and the participants were students at one nursing school in Korea. A series of course development meetings with faculties from the nursing school and the center for teaching and learning were used to develop the course format and content. We conducted course evaluations using the Flipped Course Evaluation Questionnaire with open-ended questions and focus group interviews. RESULTS: Students (N=75) in a 15-week nursing course responded to a survey after completing the course. Among them, seven students participated in one of two focus groups. Overall, students accepted and favored the flipped learning strategy, and indicated that the method enhanced lecture content and their understanding of it. Factors associated with effective instruction included structured monitoring systems and motivational environments. CONCLUSION: The FLM requires sufficient preparation to facilitate student motivation and maximize learning outcomes. PMID- 26805507 TI - Permanent leucoderma after hair transplantation surgery. PMID- 26805510 TI - Mechanical Properties and Simulated Aging of Silicone Maxillofacial Elastomers: Advancements in the Past 45 Years. AB - PURPOSE: To identify and discuss the findings of publications on mechanical behavior of maxillofacial prosthetic materials published since 1969. METHODS: Original experimental articles reporting on mechanical properties of maxillofacial prosthetic materials were included. A two-stage search of the literature, electronic and hand search, identified relevant published studies up to May 2015. An extensive electronic search was conducted of databases including PubMed, Embase, Scopus, and Google Scholar. Included primary studies (n = 63) reported on tensile strength, tear strength, and hardness of maxillofacial prosthetic materials at baseline and after aging. RESULTS: The search revealed 63 papers, with more than 28 papers being published in the past 10 years, which shows an increased number of publications when compared to only 6 papers published in the 1970s. The increase is linear with significant correlation (r = 0.85). Such an increase reflects great awareness and continued developments and warrants more research in the field of maxillofacial prosthetic materials properties; however, it is difficult to directly compare results, as studies varied in maxillofacial prosthetic materials tested with various silicone elastomers being heavily investigated, standards followed in preparing test specimens, experimental testing protocols, and parameters used in setting simulated aging conditionings. CONCLUSION: It is imperative to overcome the existing variability by establishing unified national or international standards/specifications for maxillofacial prosthetic materials. Standardization organizations or bodies, the scientific community, and academia need to be coordinated to achieve this goal. In the meantime and despite all of these theoretically significant alternatives, clinical practice still faces problems with serviceability of maxillofacial prostheses. PMID- 26805508 TI - Enhanced functional connectivity between sensorimotor and visual cortex predicts covariation bias in spider phobia. AB - The overestimation of the relationship between fear-relevant stimuli and aversive consequences, a so called covariation bias, might contribute to the maintenance of anxiety disorders. In a recent fMRI study, we confronted spider phobia and healthy participants with pictures of spiders, mushrooms and puppies, randomly followed by painful electric stimuli (US). Spider phobics overestimated the spider-US association and displayed enhanced activity in US-related sensorimotor cortex (paracentral lobule, PCL). Here, we report results from an additional functional connectivity analysis. Within spider phobics but not in healthy controls, USs after spiders led to enhanced connectivity between PCL and left prefrontal cortex (PFC). Most importantly, covariation bias in spider phobia was predicted by connectivity between PCL and visual cortex, insula, primary sensorimotor cortex and secondary somatosensory cortex. Reduced covariation bias was predicted by connectivity between PCL and PFC. In response to spider pictures, the amygdala was functionally connected to somatosensory and visual areas. These results suggest that synchronous activity of sensory cortices may promote fear-sustaining associative memory bias, while right PFC might help to reduce bias. PMID- 26805511 TI - Fixed multibracket dental therapy has challenges but can be successfully performed in young persons with Down syndrome. AB - Purpose The objective of this study was to analyze the feasibility of orthodontic treatment with fixed multibracket dental appliances (FMAs) in patients with Down syndrome (DS). Methods The study sample was formed of 25 patients with DS who underwent orthodontic treatment with FMAs. Dental and skeletal characteristics, aspects of FMA treatment, retainer use and recurrences were analyzed. Results were compared with a control group of healthy, age-, sex- and PAR index-matched individuals. Results All the controls underwent a single desensitization session, whereas 2-3 sessions were necessary in 11 patients with DS (p < 0.001). All the controls underwent bimaxillary treatment, compared with 11 patients with DS (p < 0.001). Only 8 patients with DS wore intermaxillary elastics, compared with 19 controls (p = 0.004). Complications were more common in patients with DS than in controls (p = 0.003), due particularly to traumatic ulcers development. There were more failures during the maintenance phase in patients with DS than in controls (p = 0.001). The mean duration of treatment was 37 months in patients with DS and 23 months in controls. More cemented retainers were used in the controls than in patients with DS (p = 0.050). Conclusions It is possible to perform orthodontic treatment with FMAs in patients with DS, although treatment may take longer than usual and the frequency of complications is higher than in controls. Implications for Rehabilitation Certain dental characteristics of Down syndrome (DS) make these children firm candidates for orthodontic intervention. There is little literature available on orthodontic treatment in patients with DS, particularly with regard to the use of fixed appliances. This case-control study shows that it is possible to perform orthodontic treatment with fixed appliances in adequately selected patients with DS. However, in patients with DS orthodontic treatment may take longer than usual and the frequency of complications is higher than in the general population. PMID- 26805512 TI - A prebiotic matrix for encapsulation of probiotics: physicochemical and microbiological study. AB - This work aims to develop an encapsulated oral-synbiotic supplement by studying the effect of adding inulin in alginate beads and observing its ability to protect three probiotic strains: Pediocucus acidilactici, Lactobacillus reuteri and Lactobacillus salivarius. Beads of different inulin concentrations 0%, 5%, 10%, 15% and 20% (w/v) in 2% (w/v) alginate solution were prepared by the extrusion/ionotropic gelation method. Polymer distribution within beads was characterised using confocal laser scanning microscopy. Interactions between alginate and inulin were monitored by Fourier transform infra-red spectroscopy (FTIR). Effect of encapsulation on viability, antimicrobial ability, acid tolerance and bile tolerance of probiotic strains were investigated. Antimicrobial and probiotic properties of bacterial strains were not affected by encapsulation. Bacterial protection against acidity was increased by adding inulin. Beads with 5% w/v inulin were the most effective in bacterial protection against bile-salts. To our knowledge, this work is the first to use such high concentrations of inulin. PMID- 26805513 TI - Ultra-large suspended graphene as a highly elastic membrane for capacitive pressure sensors. AB - In this work, we fabricate ultra-large suspended graphene membranes, where stacks of a few layers of graphene could be suspended over a circular hole with a diameter of up to 1.5 mm, with a diameter to thickness aspect ratio of 3 * 10(5), which is the record for free-standing graphene membranes. The process is based on large crystalline graphene (~55 MUm) obtained using a chemical vapor deposition (CVD) method, followed by a gradual solvent replacement technique. Combining a hydrogen bubbling transfer approach with thermal annealing to reduce polymer residue results in an extremely clean surface, where the ultra-large suspended graphene retains the intrinsic features of graphene, including phonon response and an enhanced carrier mobility (200% higher than that of graphene on a substrate). The highly elastic mechanical properties of the graphene membrane are demonstrated, and the Q-factor under 2 MHz stimulation is measured to be 200-300. A graphene-based capacitive pressure sensor is fabricated, where it shows a linear response and a high sensitivity of 15.15 aF Pa(-1), which is 770% higher than that of frequently used silicon-based membranes. The reported approach is universal, which could be employed to fabricate other suspended 2D materials with macro-scale sizes on versatile support substrates, such as arrays of Si nano pillars and deep trenches. PMID- 26805514 TI - DNA replication and cancer: From dysfunctional replication origin activities to therapeutic opportunities. AB - A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways to promote genome integrity during DNA replication. This includes suppressing new replication origin firing, stabilization of replicating forks, and the safe restart of forks to prevent any loss of genetic information. Here, we describe mechanisms by which oncogenes can interfere with DNA replication thereby causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy. PMID- 26805515 TI - Hitting a Moving Target: How Does an N-Methyl Group Impact Biological Activity? AB - Macrocycles have several advantages over small-molecule drugs when it comes to addressing specific protein-protein interactions as therapeutic targets. Herein we report the synthesis of seven new cyclic peptide molecules and their biological activity. These macrocycles were designed to understand how moving an N-methyl moiety around the peptide backbone impacts biological activity. Because the lead non-methylated structure inhibits the oncogenic regulator heat-shock protein 90 (Hsp90), two of the most potent analogues were evaluated for their Hsp90 inhibitory activity. We show that incorporating an N-methyl moiety controls the conformation of the macrocycle, which dramatically impacts cytotoxicity and binding affinity for Hsp90. Thus, the placement of an N-methylated amino acid within a macrocycle generates an unpredictable change to the compound's conformation and hence biological activity. PMID- 26805516 TI - Do critical care units play a role in the management of gynaecological oncology patients? The contribution of gynaecologic oncologist in running critical care units. AB - Routine post-operative care in high dependency unit (HDU), surgical intensive care unit (SICU) and intensive care unit (ICU) after high-risk gynaecological oncology surgical procedures may allow for greater recognition and correct management of post-operative complications, thereby reducing long-term morbidity and mortality. On the other hand, unnecessary admissions to these units lead to increased morbidity - nosocomial infections, increased length of hospital stay and higher hospital costs. Gynaecological oncology surgeons continue to look after their patient in the HDU/SICU and have the final role in decision-making on day-to-day basis, making it important to be well versed in critical care management and ensure the best care for their patients. Post-operative monitoring and the presence of comorbid illnesses are the most common reasons for admission to the HDU/SICU. Elderly and malnutritioned patients, as well as, bowel resection, blood loss or greater fluid resuscitation during the surgery have prolonged HDU/SICU stay. Patients with ovarian cancer have a worse survival outcome than the patients with other types of gynaecological cancer. Dependency care is a part of surgical management and it should be incorporated formally into gynaecologic oncology training programme. PMID- 26805517 TI - Facts and evidences on the lyophilization of polymeric nanoparticles for drug delivery. AB - Lyophilization has been used to improve the long-term stability of polymeric nanoparticles for drug delivery applications, avoiding their instability in suspension. However, this dehydration process may induce stresses to nanoparticles, mitigated by the use of some excipients such as cryo- and lyoprotectants. Still, the lyophilization of polymeric nanoparticles is frequently based in empirical principles, without considering the physical chemical properties of formulations and the engineering principles of lyophilization. Therefore, the optimization of formulations and the lyophilization cycle is crucial to obtain a good lyophilizate, and guarantee the preservation of nanoparticle stability. The proper characterization of the lyophilizate and nanoparticles has a great importance in achieving these purposes. This review updates the fundaments involved in the optimization procedures for lyophilization of polymeric nanoparticles, with the aim of obtaining the maximum stability of formulations. Different characterization methods to obtain and guarantee a good lyophilized product are also discussed. A special focus is given to encapsulated therapeutic proteins. Overall, this review is a contribution for the understanding of the parameters involved in the lyophilization of polymeric nanoparticles. This may definitely help future works to obtain lyophilized nanoparticles with good quality and with improved therapeutic benefits. PMID- 26805518 TI - Importance of dual delivery systems for bone tissue engineering. AB - Bone formation is a complex process that requires concerted function of multiple growth factors. For this, it is essential to design a delivery system with the ability to load multiple growth factors in order to mimic the natural microenvironment for bone tissue formation. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and high toxicity suggest that conventional routes of administration are unlikely to be effective. Therefore, it seems that using multiple bioactive factors in different delivery systems can develop new strategies for improving bone tissue regeneration. Combination of these factors along with biomaterials that permit tunable release profiles would help to achieve truly spatiotemporal regulation during delivery. This review summarizes the various dual-control release systems that are used for bone tissue engineering. PMID- 26805520 TI - Noble metal-based bimetallic nanoparticles: the effect of the structure on the optical, catalytic and photocatalytic properties. AB - Nanoparticles composed of two different metal elements show novel electronic, optical, catalytic or photocatalytic properties from monometallic nanoparticles. Bimetallic nanoparticles could show not only the combination of the properties related to the presence of two individual metals, but also new properties due to a synergy between two metals. The structure of bimetallic nanoparticles can be oriented in random alloy, alloy with an intermetallic compound, cluster-in cluster or core-shell structures and is strictly dependent on the relative strengths of metal-metal bond, surface energies of bulk elements, relative atomic sizes, preparation method and conditions, etc. In this review, selected properties, such as structure, optical, catalytic and photocatalytic of noble metals-based bimetallic nanoparticles, are discussed together with preparation routes. The effects of preparation method conditions as well as metal properties on the final structure of bimetallic nanoparticles (from alloy to core-shell structure) are followed. The role of bimetallic nanoparticles in heterogeneous catalysis and photocatalysis are discussed. Furthermore, structure and optical characteristics of bimetallic nanoparticles are described in relation to the some features of monometallic NPs. Such a complex approach allows to systematize knowledge and to identify the future direction of research. PMID- 26805521 TI - The Effects of Different Irrigation Treatments on Olive Oil Quality and Composition: A Comparative Study between Treated and Olive Mill Wastewater. AB - In the present paper, two irrigation treatments were applied to olive trees cv. Chemlali: irrigation with treated wastewater (TWW) and with olive mill wastewater (OMW), which was spread at three levels (50, 100, and 200 m(3)/ha). This work is interested in two topics: (1) the influence of different irrigation treatments on olive oil composition and quality and (2) the comparison between OMW and TWW application using different statistical analyses. The obtained variance analysis (ANOVA) has confirmed that there are no significant differences in oil quality indices and flavonoids between the control and treatments amended by OMW or TWW (p > 0.05). However, the irrigation affected some aspects of olive oil composition such as the reduction in palmitic acid (16.32%) and increase in linoleic acid (19.55%). Furthermore, the total phenols and alpha-tocopherol contents increased significantly following OMW and TWW treatments. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) defined three irrigation groups: OMW 50 and 100 m(3)/ha, OMW 200 m(3)/ha and control, and TWW treatment. The full factorial design revealed that OMW amendment by 100 m(3)/ha is the best irrigation treatment. Thus, the optimal performances in terms of olive oil quality and composition were shown by olive oil extracted from olives grown under irrigation with 100 m(3)/ha of OMW. PMID- 26805522 TI - Telocytes in ileum of the Chinese giant salamander: ultrastructural evidence. AB - Telocytes (TCs) and their telopodes (Tps) have been found in various organs of many mammals, including in lower animals. However, knowledge of TCs in lower animals is still very limited. This study identified TCs and their Tps in the ileum of the Chinese giant salamander, Andrias davidianus (Amphibia: Caudata), by transmission electron microscopy. The TCs/Tps were found near epithelial cells, glandular cells and unmyelinated nerve fibres. Moreover, exosomes were also found to be present in between TCs/Tps and these cells. PMID- 26805524 TI - Structural Insights into Outer Membrane Permeability of Acinetobacter baumannii. AB - Bacterial resistance against antibiotics is an increasing global health problem. In Gram-negative bacteria the low permeability of the outer membrane (OM) is a major factor contributing to resistance, making it important to understand channel-mediated small-molecule passage of the OM. Acinetobacter baumannii has five Occ (OM carboxylate channel) proteins, which collectively are of major importance for the entry of small molecules. To improve our understanding of the OM permeability of A. baumannii, we present here the X-ray crystal structures of four Occ proteins, renamed OccAB1 to OccAB4. In addition we have carried out a biochemical and biophysical characterization using electrophysiology and liposome swelling experiments, providing information on substrate specificities. We identify OccAB1 as having the largest pore of the Occ proteins with corresponding high rates of small-molecule uptake, and we suggest that the future design of efficient antibiotics should focus on scaffolds that can permeate efficiently through the OccAB1 channel. PMID- 26805526 TI - [Indicator and intervention in the management of critical illness]. PMID- 26805525 TI - Antarlides: A New Type of Androgen Receptor (AR) Antagonist that Overcomes Resistance to AR-Targeted Therapy. AB - Prostate cancer is treated with androgen receptor (AR) antagonists but most patients experience disease progression after long-term treatment with these compounds. Therefore, new AR antagonists are required for patient follow-up treatment. In the course of screening for a new AR antagonist, we isolated the novel compounds antarlides A-E (1-5) from Streptomyces sp. BB47. Antarlides are mutually isomeric with respect to the double bond and have a 22-membered-ring macrocyclic structure. The full stereostructure of 1 was established by chemical modifications, including methanolysis, the Trost method, acetonide formation, and the PGME method. 1-5 inhibited the binding of androgen to ARs in vitro. In addition, 2 inhibited the transcriptional activity of not only wild-type AR but also mutant ARs, which are seen in patients with acquired resistance to clinically used AR antagonists. Therefore, antarlides are a potent new generation of AR antagonists that overcome resistance. PMID- 26805527 TI - [Critical Care Medicine breakthrough in 2015]. PMID- 26805523 TI - Structural Basis of an N-Degron Adaptor with More Stringent Specificity. AB - The N-end rule dictates that a protein's N-terminal residue determines its half life. In bacteria, the ClpS adaptor mediates N-end-rule degradation, by recognizing proteins bearing specific N-terminal residues and delivering them to the ClpAP AAA+ protease. Unlike most bacterial clades, many alpha-proteobacteria encode two ClpS paralogs, ClpS1 and ClpS2. Here, we demonstrate that both ClpS1 and ClpS2 from A. tumefaciens deliver N-end-rule substrates to ClpA, but ClpS2 has more stringent binding specificity, recognizing only a subset of the canonical bacterial N-end-rule residues. The basis of this enhanced specificity is addressed by crystal structures of ClpS2, with and without ligand, and structure-guided mutagenesis, revealing protein conformational changes and remodeling in the substrate-binding pocket. We find that ClpS1 and ClpS2 are differentially expressed during growth in A. tumefaciens and conclude that the use of multiple ClpS paralogs allows fine-tuning of N-end-rule degradation at the level of substrate recognition. PMID- 26805528 TI - [Effect and mechanism of inhibition of lipopolysaccharide-induced pulmonary fibrosis by butyric acid]. AB - OBJECTIVE: To evaluate the inhibitory effect of butyric acid (BA) as a histone deacetylase (HDAC) inhibitor on lipopolysaccharide (LPS)-induced pulmonary fibrosis and its mechanism. METHODS: Thirty C57/BL6 mice were randomly divided into three groups according to the random number method, namely control group (physiological saline was given intraperitoneally and by gavage), LPS challenge group (LPS-induced murine model of pulmonary fibrosis was reproduced with intraperitoneal injection of 10 mg/kg LPS), and BA preconditioning + LPS challenge group (10 mg/kg BA was given followed by intraperitoneal injection of 10 mg/kg LPS), with 10 mice in each group. Mice were sacrificed painlessly, and lung tissue samples were harvested at 2 weeks and 4 weeks respectively (five samples every group each time). HDAC activity was evaluated with fluorescence analysis kit. Protein expression of acetylated-histone H3 (Ace-H3), acetylated histone H4 (Ace-H4) and thymocyte differentiation antigen 1 (Thy-1) were determined by Western Blot. The mRNA expression of Thy-1 was assessed by real time reverse transcription- polymerase chain reaction (real-time RT-PCR). The degree of lung inflammation and fibrosis were microscopic detected after hematoxylin-eosin (HE) staining and Masson collagen staining. The deposition of lung collagen was detected by hydroxyproline content measurement kit. RESULTS: Compared to control group, the degree of lung inflammation and fibrosis was aggravated after LPS challenge, as manifested by increased hydroxyproline content (MUg/mg, 2 weeks: 8.384+/-0.632 vs. 4.388+/-0.334, 4 weeks: 8.308+/-0.244 vs. 4.370+/-0.342, both P < 0.01), increased HDAC activity (MUmol/L, 2 weeks: 7.243+/ 0.384 vs. 3.628+/-0.641, 4 weeks: 6.479+/-0.202 vs. 3.238+/-0.524, both P < 0.01), increased deacetylation degree of histone H3 and H4 [relative expression of Ace-H3 (gray value): 0.516+/-0.115 vs. 1.005+/-0.359 at 2 weeks, 0.633+/-0.143 vs. 1.092+/-0.193 at 4 weeks, both P < 0.05; relative expression of Ace-H4 (gray value): 0.402+/-0.164 vs. 0.759+/-0.187 at 2 weeks, P > 0.05; 0.426+/-0.098 vs. 0.858+/-0.177 at 4 weeks, P < 0.01], and lowered Thy-1 mRNA and protein expression [Thy-1 mRNA (2(-DeltaDeltaCt)): 0.606+/-0.066 vs. 1.005+/-0.109 at 2 weeks, P < 0.01; 0.824+/-0.101 vs. 1.210+/-0.400 at 4 weeks, P > 0.05; relative expression of Thy-1 protein (gray value): 0.725+/-0.284 vs. 1.249+/-0.297 at 2 weeks, 0.589+/-0.139 vs. 1.372+/-0.343 at 4 weeks, both P < 0.05]. Compared with LPS group, BA precondition could inhibit above processes, as manifested by decreased hydroxyproline content (MUg/mg: 5.943+/-0.726 vs. 8.384+/-0.632 at 2 weeks, 4.938+/-0.209 vs. 8.308+/-0.244 at 4 weeks, both P < 0.01), decreased HDAC activity (MUmol/L: 4.386+/-0.117 vs. 7.243+/-0.384 at 2 weeks, 4.863+/-0.096 vs. 6.479+/-0.202 at 4 weeks, both P < 0.01), increased Thy-1 mRNA expression at 2 weeks (2(-DeltaDeltaCt): 0.884+/-0.216 vs. 0.606+/-0.066, P < 0.05), increased acetylation degree of histone H4 and Thy-1 protein expression at 4 weeks [relative expression of Ace-H4 (gray value): 0.715+/-0.145 vs. 0.426+/-0.098, P < 0.05; relative protein expression of Thy-1 (gray value): 0.939+/-0.098 vs. 0.589+/-0.139, P < 0.01]. CONCLUSIONS: LPS-induced pulmonary fibrosis was related with activation of HDAC, deacetylation of histone H3 and H4 and Thy-1 gene silencing. HDAC inhibitor BA could inhibit LPS-induced pulmonary fibrosis and Thy 1 gene silencing through inhibiting activation of HDAC and deacetylation of histone H4. PMID- 26805529 TI - [The clinical effect of airway pressure release ventilation for acute lung injury/acute respiratory distress syndrome]. AB - OBJECTIVE: To evaluate the effect of airway pressure release ventilation (APRV) in patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS), to evaluate the extent of ventilator-induced lung injury (VILI), and to explore its possible mechanism. METHODS: A prospective study was conducted in the Department of Critical Care Medicine of the First Hospital of Hebei Medical University from December 2010 to February 2012. The patients with ALI/ARDS were enrolled. They were randomly divided into two groups. The patients in APRV group were given APRV pattern, while those in control group were given lung protection ventilation, synchronized intermittent mandatory ventilation with positive end expiratory pressure (SIMV+PEEP). All patients were treated with AVEA ventilator. The parameters such as airway peak pressure (Ppeak), mean airway pressure (Pmean), pulse oxygen saturation (SpO2), mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), arterial blood gas, urine output (UO), the usage of sedation and muscle relaxation drugs were recorded. AVEA ventilator "turning point (Pflex) operation" was used to describe the quasi-static pressure volume curve (P-V curve). High and low inflection point (UIP, LIP) and triangular Pflex volume (Vdelta) were automatically measured and calculated. The ventilation parameters were set, and the 24-hour P-V curve was recorded again in order to be compared with subsequent results. Venous blood was collected before treatment, 24 hours and 48 hours after ventilation to measure lung surfactant protein D (SP-D) and large molecular mucus in saliva (KL-6) by enzyme linked immunosorbent assay (ELISA), and the correlation between the above two parameters and prognosis on 28 days was analyzed by multinomial logistic regression. RESULTS: Twenty-six patients with ALI/ARDS were enrolled, and 22 of them completed the test with 10 in APRV group and 12 in control group. The basic parameters and P-V curves between two groups were similar before the test. After 24 hours and 48 hours, mechanical ventilation was given in both groups. The patients' oxygenation was improved significantly, though there were no significant changes in hemodynamic parameters. The Pmean (cmH2O, 1 cmH2O = 0.098 kPa) in APRV group was significantly higher than that in control group (24 hours: 24.20+/-4.59 vs. 17.50+/-3.48, P < 0.01; 48 hours: 18.10+/-4.30 vs. 15.00+/-2.59, P < 0.05). After ventilation for 24 hours, the ratio of patients with increased Vdelta in APRV group was higher than that in control group (90% vs. 75%), but without statistical difference (P > 0.05). The SP-D level (MUg/L) in serum in APRV group showed a tendency of increase (increased from 19.70+/-7.34 to 27.61+/-10.21, P < 0.05), in contrast there was a tendency of decrease in control group (decreased from 21.83+/-7.31 to 16.58+/-2.90, P > 0.05), the difference between the two groups was statistically significant (P < 0.05). After 48-hour ventilation, SP-D in APRV group was decreased, but no change was found in control group, and no significant difference was found as compared with that of the control group (16.45+/-8.17 vs. 17.20+/-4.59, P > 0.05). There was no significant difference in serum KL-6 between the two groups before and after ventilation. The SP-D and KL-6 levels in serum were unrelated with 28-day survival rate of the patients. The odds ratio (OR) of SP-D were 0.900 [95% confidence interval (95%CI) = 0.719 1.125], 1.054 (95%CI = 0.878-1.266), 1.143 (95%CI = 0.957-1.365), and the OR of KL-6 were 1.356 (95%CI = 0.668-2.754), 0.658 (95%CI = 0.161-2.685), 0.915 (95%CI = 0.350-2.394) before the test, 24 hours and 48 hours after ventilation (all P > 0.05). CONCLUSIONS: APRV was similar to lung protective ventilation strategy in oxygenation and improvements in the lung mechanics parameters. APRV with a higher Pmean can recruit alveolar more effectively, and it had no impact on hemo dynamics, but might exacerbate VILI. PMID- 26805530 TI - [The value of N-terminal pro-B type natriuretic peptide in predicting the outcome of spontaneous breathing trials in elderly renal dysfunction patients]. AB - OBJECTIVE: To investigate the value of N-terminal pro-B type natriuretic peptide (NT-proBNP) in predicting the outcome of spontaneous breathing trial (SBT) in ventilated elderly renal dysfunction patients. METHODS: The clinical data of patients who received mechanical ventilation in the Department of Critical Care Medicine of the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Disease from January 2011 to December 2014 were analyzed retrospectively. AU the patients conformed to the following criteria: age > 65 years, endogenous creatinine clearance rate (CCr) < 60 mL*min( 1)*1.73 m(-2), the duration of mechanical ventilation > 72 hours and undergone at least one SBT. The patients were assigned to a SBT success group and a SBT failure group according to the outcome of first SBT. The following factors were recorded: gender, age, the underlying disease [chronic obstructive pulmonary disease (COPD), heart failure (HF) and others], body mass index (BMI), serum pre albumin (pre-ALB), and acute physiology and chronic health evaluation II (APACHE II) score, CCr and the concentration of the plasma NT-proBNP before SBT. Receiver operator characteristic curve (ROC) was plotted, and the predict value of NT proBNP for the outcome of SBT in elder patients with kidney dysfunction was determined. RESULTS: A total of 58 patients with complete data were enrolled, with 41 cases in SBT success group, and 17 in SBT failure group. There were no significant differences in gender [male/female (cases): 26/15 vs. 13/4, chi (2) = 0.930, P = 0.335], age (years: 70.2+/-7.4 vs. 74.6+/-10.1, t = 0.833, P = 0.339), the stratification of underlying diseases [COPD/HF/COPD+HF/others (cases): 15/9/13/4 vs. 7/3/5/2, chi (2) = 0.242, P = 0.971], BMI (kg/m(2): 25.2+/-11.3 vs. 27.4+/-6.43, t = 1.038, P = 0.221), pre-ALB (mg/L: 201.0+/-13.2 vs. 189.0+/-7.6, t = 0.688, P = 0.519), and APACHE II score (12.2+/-3.2 vs. 13.5+/-6.3, t = 1.482, P = 0.147) and CCr (mL*min(-1)*1.73 m(-2): 51.3+/-7.7 vs. 54.2+/-6.4, t = 0.711, P = 0.487) before SBT between SBT success group and SBT failure group. The concentration of plasma NT-proBNP in SBT failure group was significantly higher than that of the SBT success group (MUg/L: 4.162+/-1.128 vs. 2.284+/-1.399, t = 4.905, P = 0.000). The area under ROC curve for plasma NT-proBNP in predicting successful SBT among elder patients with kidney dysfunction was 0.878, with 95% confidence interval (95%CI) 0.786 - 0.970. The cut-off method was used, and it was identified that the concentration of NT-proBNP < 3.350 MUg/L as a predictor for successful SBT, with sensitivity of 82.4%, specificity of 87.8%, positive prediction value of 88.1% and negative predictive value of 76.5%. CONCLUSIONS: The concentration of plasma NT-proBNP may increase in elderly kidney dysfunction patients undergoing ventilation, and NT-proBNP < 3.350 MUg/L can serve as a good predictor for SBT success. PMID- 26805531 TI - [A simple and controllable method for reproduction of a model of high oxygen tension induced acute lung injury]. AB - OBJECTIVE: To explore a simpler, more economic and reproducible method to reproduce a model of high oxygen induced acute lung injury (HALI) in rats. METHODS: An animal feeding box equipped with a controllable high oxygen was designed. 100 Sprague-Dawley (SD) rats were divided into normal control group and HALI group by random number table method, with 50 rats in each group. Each group was randomly subdivided into five subgroups according to the duration of exposure to high oxygen, namely 0, 24, 48, 72 and 96-hour subgroups, with 10 rats in each subgroup. The rats in normal control group were kept in cages with ambient air, and the rats in HALI group were kept in an oxygen tank in which the oxygen concentration was higher than 90% volume ratio, with the temperature maintained at 25-27?centigrade, humidity of 50%-70%, and CO2 concentration < 0.5% for 23.5 hours every day. The arterial blood of rats was collected for analysis of blood gas at all time points, and the oxygenation index (OI) and respiratory index (RI) were calculated. Then the rats were sacrificed and the right lung was harvested, which was sectioned and stained with hematoxylin and eosin (HE). The changes in histopathology were observed with light microscopy, and pathological score was recorded. The left lung was harvested for the measurement of the wet/dry weight ratio (W/D). RESULTS: With the prolongation of high oxygen exposure time, the degree of lung injury in HALI group was gradually increased, and the degree of derangement of alveolar structure appeared in an increasing degree, with destruction of the alveolar wall, widening of alveolar space, and appearance of edema, and inflammatory cell infiltration. A small quantity of red blood cells exudation could be found in some rats. The pathologic changes were most obvious at 48-72 hours after exposure. With the prolongation of high oxygen exposure time (0, 24, 48, 72, 96 hours), the OI (mmHg, 1 mmHg = 0.133 kPa) in HALI group was gradually decreased (446.67+/-29.93, 306.19+/-37.23, 269.70+/-29.00, 253.81+/ 43.40 and 245.58+/-35.25), RI, pathological score of lung tissue and W/D ratio were gradually increased [RI: 0.25+/-0.04, 0.31+/-0.06, 0.38+/-0.06, 0.46+/-0.07 and 0.44+/-0.03; pathological score of lung tissue: 0.00+/-0.00, 0.90+/-0.74, 2.90+/-1.20, 4.70+/-1.57 and 4.80+/-1.23; lung W/D ratio: 3.84+/-0.61, 4.14+/ 0.46, 4.56+/-0.34, 5.32+/-0.27 and 5.18+/-0.25]. Statistically significant differences were found in 72-hour group as compared with that of other groups (all P < 0.05), while no significant difference was found between 96 hours and 72 hours groups (all P > 0.05). There were significant differences in changes between 24, 48, 72, and 96 hours as compared with those of the normal control group: OI (mmHg): 24 h 306.19+/-37.23 vs. 435.65+/-25.34 and 96 h 245.58+/-35.25 vs. 465.42+/-24.75; RI: 24 h 0.31+/-0.06 vs. 0.24+/-0.04 and 96 h 0.44+/-0.03 vs. 0.24+/-0.06. The same as true in pathological scores of lung tissue: 24 h 0.90+/ 0.74 vs. 0.00+/-0.00 and 96 h 4.80+/-1.23 vs. 0.00+/-0.00; lung W/D ratio: 24 h 4.14+/-0.46 vs. 3.79+/-0.44 and 96 h 5.18+/-0.25 vs. 4.12+/-0.91, all P < 0.05. CONCLUSIONS: A self-designed high oxygen box is simple, easy to operate and reproduction of HALI model can be attained. Sustained exposure to high concentrations of oxygen (>= 90%) for 24 hours can replicate the HALI model successfully, and the most serious injury appears at 48-72 hours after exposure. PMID- 26805532 TI - [The effect of resveratrol on paraquat-induced acute lung injury in mice and its mechanism]. AB - OBJECTIVE: To investigate the effect of resveratrol (Res) on paraquat (PQ) induced acute lung injury (ALI) and mortality in mice and the mechanism of nuclear factor-KappaB (NF-KappaB) inflammatory pathway. METHODS: Sixty-eight healthy male ICR mice with grade SPF were enrolled, among them 20 mice were used for mortality observation (n = 10), and other 48 were used for determination of related parameters (n = 6). The mice were randomly divided into four groups: normal saline (NS) control group, Res control group, PQ group and PQ + Res group. The mice in the latter two groups were subdivided into 6, 24, 72 hours subgroups. The PQ poisoning model of mice was reproduced by one injection of 30 mg/kg PQ intraperitoneally. The mice in PQ + Res group were given 60 mg/kg Res intraperitoneally on the contralateral side after PQ injection. The mice were sacrificed at 6, 24, 72 hours after PQ poisoning, and lung tissue was harvested. The serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukins (IL-6 and IL-1beta) were determined by enzyme linked immunosorbent assay (ELISA). The pathological changes in lung tissue were observed with electron microscopy. Apoptosis cells in the lung were identified by terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) for the estimation of apoptosis rate. The protein expression of NF-KappaB p65 was determined by Western Blot. RESULTS: Compared with PQ group, the death number of mice at 48, 72, 96 hours in PQ + Res group was slightly decreased (0 vs. 2, 2 vs. 5, 4 vs. 6) but without statistically significant difference (all P > 0.05). Under electron microscope, the lung injury in PQ group was severer than that in NS control group, and Res was found to be able to alleviate the lung injury. Compared with NS control group [(2.45+/-0.61)%], the apoptosis rate at 6 hours in PQ group was significantly increased [(8.42+/-1.48)%], and peaked at 72 hours [(21.23+/ 3.47)%]. Res could decrease the apoptosis rate after PQ poisoning [6 hours: (5.56+/-1.31)% vs. (8.42+/-1.48)%, 24 hours: (11.14+/-2.07)% vs. (16.88+/-2.96)%, 72 hours: (13.28+/-2.32)% vs. (21.23+/-3.47)%, all P < 0.05]. The serum levels of TNF-alpha, IL-6, and IL-1beta, and NF-KappaB p65 in lung tissue were all markedly increased after PQ poisoning, and they were significantly decreased after Res intervention as compared with those of PQ group [TNF-alpha (ng/L): 2.62+/-0.29 vs. 4.06+/-0.74 at 6 hours, 3.98+/-0.41 vs. 6.79+/-0.80 at 24 hours, 5.06+/-0.75 vs. 11.00+/-0.75 at 72 hours; IL-6 (ng/L): 14.19+/-1.54 vs. 16.55+/-1.24 at 6 hours, 13.21+/-1.37 vs. 19.73+/-0.85 at 24 hours, 13.72+/-0.56 vs. 22.45+/-0.72 at 72 hours; IL-1beta (ng/L): 8.54+/-1.64 vs. 12.59+/-0.66 at 6 hours, 10.15+/ 0.29 vs. 16.24+/-1.03 at 24 hours, 16.14+/-0.70 vs. 19.55+/-0.56 at 72 hours; 6 hour NF-KappaB p65: (1.34+/-0.07) folds vs. (1.86+/-0.11) folds when the expression in NS control group was represented as 1, all P < 0.05]. CONCLUSIONS: Res cannot lower the mortality in mice with PQ poisoning, but it seems to be able to attenuate PQ-induced ALI and cell apoptosis. The mechanism responsible for the latter maybe the inhibitive effect of Res on NF-KappaB p65 translocation and cytokines production. PMID- 26805533 TI - [The value of determination of serum cholinesterase levels in judgment of severity and prognosis in patients with severe pneumonia]. AB - OBJECTIVE: To investigate the value of serum cholinesterase (S-ChE) levels in judgment of severity and prognosis in patients with severe pneumonia. METHODS: The clinical data of patients with severe pneumonia, who were admitted to the Department of Internal Medicine in the First Affiliated Hospital of Sun Yat-sen University, or the Department of Neurology in the Third People's Hospital of Foshan from May 2011 to May 2015, whose hospital time was longer than 24 hours, were retrospectively analyzed. They were divided into survival group and death group according to the final outcome. Lab data, acute physiology and chronic health evaluation II (APACHE II) score, multiple organ dysfunction syndrome (MODS) score, the improved pneumonia score of British Thoracic Society (confusion, uremia, respiratory, blood pressure, age 65 years, CURB-65), and S ChE levels of all patients were collected after they were hospitalized into the intensive care unit (ICU) within 24 hours. Independent risk factors for prognosis were analyzed by binary logistic regression analysis, and receiver operating characteristic curve (ROC) was plotted. Best truncation point analysis was used to compare their estimated value for prognosis of patients with severe pneumonia. RESULTS: Eighty-six patients with severe pneumonia were studied. Among them 46 patients survived, and 40 patients died. By the single factor analysis, the following lab data in the death group were found significantly lower than those in the survival group: S-ChE levels (kU/L: 2.748+/-0.826 vs. 4.489+/-1.360, t' = 7.274, P = 0.000), arterial partial pressure of oxygen [PaO2 (mmHg, 1 mmHg = 0.133 kPa): 52.55+/-18.29 vs. 60.83+/-16.65, t = 2.196, P = 0.031], oxygenation index (mmHg: 114.20+/-48.01 vs. 167.10+/-69.68, t' = 4.229, P = 0.000), and carbon dioxide combining power [CO2-CP (mmol/L): 22.85+/-5.44 vs. 26.00+/-7.63, t' = 2.225, P = 0.029]. The following clinical data were significantly higher in the death group than those in the survival group, namely body temperature (centigrade: 38.67+/-1.18 vs. 37.74+/-1.18, t = -3.627, P = 0.000), pulse (bpm: 130.65+/-15.72 vs. 107.26+/-19.61, t' = -6.133, P = 0.000), the ratio of concomitant chronic lung disease [45.0% (18/40) vs. 13.0% (6/46), chi(2) = 10.860, P = 0.001], fraction of inspired oxygen [FiO2: 0.495 (0.410, 0.600) vs. 0.380 (0.290, 0.500), Z = -3.265, P = 0.001], APACHE II score (25.80+/-5.07 vs. 16.39+/-5.12, t =-8.540, P = 0.000), CURB-65 score [3 (3, 4) vs. 2 (1, 2), Z = 5.562, P = 0.000], MODS score (8.15+/-2.49 vs. 4.35+/-2.01, t = -7.832, P = 0.000), international normalized ratio [INR: 1.22 (1.08, 1.31) vs. 1.07 (1.00, 1.10), Z = -4.231, P = 0.000], and activated partial thromboplastin time [APTT (s): 33.80 (32.13, 38.75) vs. 28.50 (25.70, 36.00), Z = -3.482, P = 0.000]. Binary logistic regression analysis showed that, S-ChE levels, APACHE II score and MODS score were found to be the independent risk factors for prognosis in the patients with severe pneumonia, respectively [S-ChE: odds ratio (OR) = 0.084, 95% confidence interval (95%CI) = 0.017-0.424, P = 0.003; APACHE II score: OR = 1.675, 95%CI = 1.098-2.556, P = 0.017; MODS score: OR = 2.189, 95%CI = 1.262 3.800, P = 0.005]. The area under ROC (AUC) for S-ChE levels, APACHE II score and MODS score were 0.874+/-0.036, 0.889+/-0.033 and 0.884+/-0.035, respectively (all P > 0.05 as compared between any two means). At the best truncation points of S ChE levels, APACHE II score and MODS score were 3.372 kU/L, 19.5 score, and 6.5 score respectively. The sensitivity, specificity, positive predictive value and negative predictive value in predicting death risk in patients with severe pneumonia were (80.0%, 78.0%, 76.19% and 81.82%), (95.0%, 70.0%, 73.08% and 94.12%) and (70.0%, 91.0%, 87.50%, 77.78%), respectively. If S-ChE levels was combined with APACHE II score or combined with MODS score, the sensitivity, specificity, positive predictive value and negative predictive value [S-ChE levels combined APACHE II score: 100%, 92.0%, 93.75% and 100%; S-ChE levels combined MODS score: all 100%] were higher than single power of S-ChE levels, APACHE II score or MODS score. CONCLUSIONS: S-ChE levels can be considered as an effective and practical index to estimate the severity and prognosis in patients with severe pneumonia. The combined application of S-ChE levels and APACHE II score or MODS score can obviously improve the prognostic power in patients with severe pneumonia. PMID- 26805534 TI - [The value of a tool for evaluation of pain in patients undergone craniotomy]. AB - OBJECTIVE: To determine the optimal cut-off value of critical-care pain observation tool (CPOT) in assessing degree of pain in patients undergone craniotomy, and to determine the sensitivity and specificity of CPOT with this cut-off value. METHODS: A prospective observational study was conducted in Beijing Tiantan Hospital. A total of 118 patients admitted to intensive care unit (ICU) after craniotomy was consecutively enrolled during August 2014 to August 2015. CPOT and visual analogue scale (VAS) were used to assess the pain before, during and 20 minutes after the removal of central venous catheters, and the difference was compared between two scores at three time points. Receiver operating characteristic (ROC) curve was used to determine the optimal cut-off values for evaluation of the sensitivity and specificity of CPOT. Patients' complaint of pain was considered the "gold-standard". RESULTS: CPOT values (inter quartile range) before, during and after the procedure were 0 (0-3), 0 (0-6) and 0 (0-2), respectively; while VAS values were 4 (1, 6), 3 (1, 6) and 4 (1, 6), respectively. CPOT value during the procedure was significantly higher than CPOT values before and after the procedure (both P < 0.01). When the optimal cut-off value of CPOT was 1, CPOT showed the highest Youden index before, during and after the procedure (1.183, 1.515, and 1.438, respectively), and showed high specificity (all 100%) and low sensitivity (18.3% and 43.8%, respectively) when assessing the pain before and after the removal of the catheter. The sensitivity and the specificity were high when assessing the pain during the procedure, the sensitivity was 69.4%, and the specificity was 82.1%. When the optimal cut-off value of VAS was 2 before and during the procedure, and was 4 after the procedure, VAS showed the highest Youden index, 1.568, 1.452, and 1.509, respectively. VAS demonstrated high sensitivity and specificity before, during and after the procedure (sensitivity was 97.2%, 95.2% and 75.0%, respectively; specificity was 59.6%, 50.0% and 75.9%, respectively). The area under ROC curve (AUC) of CPOT before, during and after the procedure were 0.592 [95% confidence interval (95%CI) = 0.490-0.693], 0.778 (95%CI = 0.693-0.863) and 0.719 (95%CI = 0.627-0.811), respectively; the AUC of VAS before, during and after the procedure were 0.846 (95%CI = 0.771-0.920), 0.767 (95%CI = 0.681-0.854) and 0.838 (95%CI = 0.767-0.909), respectively. The AUC of VAS before and after the procedure was significantly higher than the AUC of CPOT (P < 0.001 and P = 0.006), while there was no significant difference between the AUC of VAS and CPOT during the procedure (P = 0.826). CONCLUSIONS: CPOT can be used to assess the pain during painful procedure, and it shows high accuracy, but with poor evaluation effect on pain in rest. PMID- 26805535 TI - [Study of prevention and control of delirium in ventilated patients by simulating blockage of circadian rhythm with sedative in intensive care unit]. AB - OBJECTIVE: To explore the effect of giving sedatives according to the circadian rhythm in prevention of occurrence of delirium and the prognosis of patients undergoing mechanical ventilation in intensive care unit (ICU). METHODS: A prospective double-blinded randomized controlled trial (RCT) was conducted. The patients admitted to Department of Critical Care Medicine of the Second Hospital of Lanzhou University from July 2014 to February 2015, undergoing invasive mechanical ventilation over 12 hours were enrolled. All the patients were given fentanyl for analgesia, and they were randomly divided into simulated circadian clock group (study group, n = 35) and non-simulated circadian clock group (control group, n = 35). The patients in each group were subdivided into three subgroups according to the kinds of sedative drugs, namely dexmedetomidine group (n = 8), propofol group (n = 14), and dexmedetomidine combined with propofol group (combination group, n = 13). Visual analogue scale (VAS) standard and Richmond agitation-sedation scale (RASS) were used to control the analgesic and to quantify the depth of sedation by titrating the dose of sedative drugs, the simulated circadian clock was set to control the RASS score at 0-1 during the day, and -1 to -2 at night in study group. The RASS score in the control group was set at -1 to -2 day and night. The urine 6-hydroxy acid melatonin (aMT6s) levels at different time points in the first diurnal rhythm (06:00, 12:00, 18:00, 24:00) were determined by enzyme linked immunosorbent assay (ELISA). The incidence of delirium, severe hypotension, severe bradycardia and other adverse reactions, duration of mechanical ventilation and the time of extubation, length of ICU stay, amount of sedative and analgesic drugs used were recorded. The correlation between delirium and other indexes was analyzed by using Spearman correlation analysis. RESULTS: (1) There were no significant differences in gender, age, acute physiology and chronic health evaluation II (APACHEII) score among groups. (2) Urine aMT6s levels did not show circadian rhythm in both groups, aMT6s level at 06:00 in study group showed an increasing tendency as compared with the control group, but the difference was not statistically significant. (3) Compared with the control group, the incidence of delirium was significantly lowered in the study group (14.3% vs. 37.1%, P = 0.029), but no significant differences were found in the incidence of severe hypotension or severe bradycardia (20.0% vs. 25.7%, 11.4% vs. 20.0%, both P > 0.05). In simulated circadian clock group, the incidence of delirium in dexmedetomidine group was significantly lower than that of the propofol group (6.3% vs. 32.1%, P < 0.05). (4) Compared with control group with the same sedative, the duration of mechanical ventilation, extubation time, length of ICU stay were significantly shortened, and the dosage of sedative drugs used was reduced in study group (all P < 0.05). In simulated circadian clock group, the duration of mechanical ventilation in dexmedetomidine group was significantly shorter than that of propofol group and combination group (hours: 75.75+/-26.78 vs. 102.00+/-26.31 and 100.31+/-25.38, both P < 0.05), and the length of ICU stay was significantly shorter than that of propofol group (days: 5.75+/-1.04 vs. 7.00+/-1.52, P < 0.05). (5) The occurrence of delirium was positively correlated with duration of mechanical ventilation (r = 0.705), extubation time (r = 0.704), length of ICU stay (r = 0.666, all P = 0.000), and no correlation was found between the occurrence of delirium and aMT6s level at 06:00, 12:00, 18:00, and 24:00 (r = 0.135, r = 0.163, r = 0.269, r = -0.077, all P > 0.05). CONCLUSIONS: Administration of sedatives according to simulating circadian time could decrease the duration of mechanical ventilation, extubation time, and the length of ICU stay, decrease the dosage of sedative drugs, and reduce the incidence of delirium. Dexmedetomidine could reduce the incidence of delirium, and improve the prognosis of patients. PMID- 26805536 TI - [Effect of noninvasive ventilation on hypercapnic encephalopathy syndrome: a Meta analysis]. AB - OBJECTIVE: To evaluate the effect of noninvasive ventilation (NIV) on hypercapnic encephalopathy syndrome (HES) induced by acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: An extensive search of related literature from the PubMed, EMBASE, Cochrane library, CNKI and Wanfang databases up to January 2015 was performed. Randomized controlled trials (RCTs) and case control studies regarding comparison of the effect of NIV and conventional mechanical ventilation (CMV) on the HES were collected. Critical appraisal skills program (CASP) was adopted to assess the quality of the studies. Data including mortality, trachea intubation rate, duration of mechanical ventilation and complication rate were collected, and Meta-analysis was performed by RevMan 5.3. RESULTS: Finally, 6 studies were included with 225 subjects, among whom 112 were in NIV group and 113 in CMV group, and the average Kelly-Matthay score was 3. Compared with CMV group, the mortality [20.5% (23/112) vs. 32.7% (37/113), risk ratio (RR) = 0.63, 95% confidential interval (95%CI) = 0.40-0.98, P = 0.04], intubation rate [35.7% (40/112) vs. 100.0% (113/113), RR = 0.38, 95%CI = 0.26 0.55, P < 0.000?01], incidence of ventilation related complications [26.2% (21/80) vs. 50.6% (42/83), RR = 0.52, 95%CI = 0.34-0.79, P = 0.002] in NIV group were significantly decreased, and the duration of mechanical ventilation was significantly shortened [days: 7.1 vs. 16.2, standard mean difference (SMD) = 0.93, 95%CI = -1.39 to -0.46, P < 0.000?1]. CONCLUSIONS: NIV could significantly lower the mortality rate, intubation rate, and complications in the treatment of HES induced by AECOPD under close monitoring. PMID- 26805537 TI - [Effects of two different methods for airway humidification for patients with tracheostomy: a Meta-analysis]. AB - OBJECTIVE: To evaluate the effects of two different kinds of airway humidification for tracheostomy patients, and to provide their relevant clinical effect and suggestions for their use. METHODS: Online databases, including PubMed, EMBASE, JBI evidence-based nursing center library, the Cochrane Library, and Chinese databases (CNKI, Wanfang database, VIP, CBM) were searched systematically up to March 2015. Randomized controlled trials (RCTs) were considered eligible for inclusion if the following criteria were met: no history of respiratory tract infection; satisfactory nutritional status; tracheotomy performed; 18 years older. Two different humidification methods were used. Continuous airway humidification was used in the experiment group, while intermittent airway humidification was used in the control group. Two qualified reviewers reviewed the original articles, evaluating the quality of articles, and data were extracted independently. The enrolled RCTs were analyzed by Meta analysis. RESULTS: A total of nine RCTs were included, containing 631 cases, among them 316 cases in expertment group, and 315 cases in control group. Continuous airway humidification was shown to be able to reduce the incidence of irritable cough [odds ratio (OR) = 0.20, 95% confidence interval (95%CI) = 0.12 0.34, P < 0.000?01], bleeding form mucosa of respiratory tract (OR = 0.25, 95%CI = 0.14-0.45, P < 0.000?01), sputum conglomeration (OR = 0.19, 95%CI = 0.10-0.39, P < 0.000?01), and pneumonia (OR = 0.29, 95%CI = 0.19-0.45, P < 0.000?01). The funnel plots were largely symmetrical, suggesting there was no publication bias in the Meta-analysis of two methods for airway humidification for tracheostomy patients. CONCLUSIONS: Because the number of including articles was relative small, and the quality of some articles was poor, it is impossible to draw a reliable conclusion that continuous airway humidification could lower the incidence of complications for patients undergone tracheostomy. PMID- 26805538 TI - [Analysis of the causes of defficult withdrawal from mechanical ventilation after cardiac surgery]. PMID- 26805539 TI - [Clinical analysis of severe plastic bronchitis in 8 children]. PMID- 26805540 TI - [Design and study of a new device for low temperature intravenous infusion]. PMID- 26805541 TI - [The obtimal site for peripheral venous puncture for intravenous amiodarone injection]. PMID- 26805542 TI - [Successful sequential weaning from invasive and non-invasive ventilation in a difficult airway patient: report of one case]. PMID- 26805543 TI - [The application of actively heated humidified high flow nasal cannula oxygen therapy in adults]. AB - OBJECTIVE: Actively heated, humidified high flow nasal cannula oxygen therapy (HFNC) is a new type of oxygen therapy. Because of its unique physiological effects, the clinical application is becoming more and more popular. This article is to summarize the physiological effects, clinical application and short comings of HFNC. Compared with conventional oxygen therapy, HFNC helps to improve oxygenation better, and it is more comfortable than non-invasive ventilation (NIV) in use. Proper use of HFNC may be able to reduce the use of NIV and decrease the rate of endotracheal intubation. It can be used for adults with mild to moderate hypoxia, or for patients undergoing palliative care. However, the experience of the use of HFNC in adults is limited, and there is yet no corresponding clinical guideline. Therefore, further research with a large sample is required to determine the long-term effect of this technique, and to identify the adult patient population to whom is most beneficial. PMID- 26805544 TI - [The progress of light sedation for critically ill adult patients in intensive care unit]. AB - OBJECTIVE: The latest advance of sedation for critically ill adult patients in intensive care unit (ICU) was reviewed in order to provide certain clinical information for the ICU physicians about sedation. Guidelines, clinical research, Meta-analysis, and reviews in recent years were collected using electronic data base. Discussions included: (1) the definition of light sedation, and its effects on clinical outcome, stress, sleep and delirium; (2) light sedation strategies included: the target population, the target sedation strategy and daily sedation interruption, clinical assessment and monitoring of sedation, selection of sedative drugs, light sedation extenuation; (3) light sedation strategies and pain, agitation, delirium control bundles; (4) the problems and prospects of light sedation. Light sedation is the main principle of currently ICU sedation strategy in critically ill adult patients. Goal-directed light sedation should be considered as a routine therapy in most clinical situation, and its goal should be achieved as early as possible in the early stage of sedation. Routine use of benzodiazepines should be avoided, especially in patients with or at a risk of delirium. Prevention and treatment of agitation with a combination of non pharmacologic or pharmacologic methods; ICU specification rules for pain, agitation and delirium prevention and treatment should be made. Light sedation is the main ICU sedation strategy in adult patients now, but must be individualized for each patient. PMID- 26805545 TI - Contralateral bone widening and transfer for limb sparing in a cat. AB - OBJECTIVE: To report on a novel surgical procedure to treat a long segmental tibial defect in a five-year-old 5 kg spayed female Main Coon cat using transverse distraction osteogenesis in the contralateral tibia to create a free autograft. METHODS: A long free bone segment was created from the cranial half of the normal tibia. A circular external fixator was constructed to give the segment 7 mm of cranial distraction. After 42 days the widened section of tibial bone was removed and transferred to the defect in the contralateral tibia. Locking plates were used to stabilize the graft and to protect the donor tibial sites. RESULTS: By 27 months, both tibias were healed, all implants had been removed, function was excellent, and the overall limb length was 90% of the normal side. CLINICAL RELEVANCE: Compared with longitudinal distraction osteogenesis in long bone defects, transverse distraction of a normal bone requires a significantly shorter distraction distance to produce a similar amount of bone. Thus, distraction time is reduced, with less likelihood of significant soft tissue damage. New bone may be more reliably regenerated in a normal limb due to better tissue health, and native bone may be more readily incorporated than allografts in compromised sites. Disadvantages include the increased morbidity, as well as the risk and expense associated with involvement of a normal limb. PMID- 26805546 TI - Direct fabrication of 3D graphene on nanoporous anodic alumina by plasma-enhanced chemical vapor deposition. AB - High surface area electrode materials are of interest for a wide range of potential applications such as super-capacitors and electrochemical cells. This paper describes a fabrication method of three-dimensional (3D) graphene conformally coated on nanoporous insulating substrate with uniform nanopore size. 3D graphene films were formed by controlled graphitization of diamond-like amorphous carbon precursor films, deposited by plasma-enhanced chemical vapour deposition (PECVD). Plasma-assisted graphitization was found to produce better quality graphene than a simple thermal graphitization process. The resulting 3D graphene/amorphous carbon/alumina structure has a very high surface area, good electrical conductivity and exhibits excellent chemically stability, providing a good material platform for electrochemical applications. Consequently very large electrochemical capacitance values, as high as 2.1 mF for a sample of 10 mm(3), were achieved. The electrochemical capacitance of the material exhibits a dependence on bias voltage, a phenomenon observed by other groups when studying graphene quantum capacitance. The plasma-assisted graphitization, which dominates the graphitization process, is analyzed and discussed in detail. PMID- 26805547 TI - Coccydynia related to the use of a contraceptive vaginal ring. AB - Coccydynia is a syndrome that rheumatologists encounter frequently in the form of tailbone pain, which is usually worse when sitting. Although the most common origin is trauma, there are several other possible causes of pain in the coccyx. We present an unusual case in which coccydynia developed shortly after the insertion of a contraceptive vaginal ring and remitted completely upon removal of this system. PMID- 26805550 TI - Phenotypic Characterization Analysis of Human Hepatocarcinoma by Urine Metabolomics Approach. AB - Hepatocarcinoma (HCC) is one of the deadliest cancers in the world and represents a significant disease burden. Better biomarkers are needed for early detection of HCC. Metabolomics was applied to urine samples obtained from HCC patients to discover noninvasive and reliable biomarkers for rapid diagnosis of HCC. Metabolic profiling was performed by LC-Q-TOF-MS in conjunction with multivariate data analysis, machine learning approaches, ingenuity pathway analysis and receiver-operating characteristic curves were used to select the metabolites which were used for the noninvasive diagnosis of HCC. Fifteen differential metabolites contributing to the complete separation of HCC patients from matched healthy controls were identified involving several key metabolic pathways. More importantly, five marker metabolites were effective for the diagnosis of human HCC, achieved a sensitivity of 96.5% and specificity of 83% respectively, could significantly increase the diagnostic performance of the metabolic biomarkers. Overall, these results illustrate the power of the metabolomics technology which has the potential as a non-invasive strategies and promising screening tool to evaluate the potential of the metabolites in the early diagnosis of HCC patients at high risk and provides new insight into pathophysiologic mechanisms. PMID- 26805551 TI - Nanosize of zinc oxide and the effects on zinc digestibility, growth performances, immune response and serum parameters of weanling piglets. AB - The aim of this study was to investigate the effect of dietary supplementation of nanosize zinc on zinc digestibility, growth performances, immune response and serum parameters of weanling piglets. Ninety-six LYD weanling piglets were assigned to control, zinc oxide (ZnO), organic-Zn (Zn-methionine) and nanosize ZnO (nano-Zn) groups with four replicates. The zinc was at the 120 mg/kg level in the treatment group's diet, while the control group's was 80 mg/kg Zn. The experiment results indicated that the nano-Zn and organic-Zn groups had significantly higher Zn digestibility compared to the ZnO and control groups. For the immune response traits, the IgG level and goat red blood cells (GRBC) antibody titer were nano-Zn and organic-Zn>ZnO>control; in the phytohemagglutinin (PHA) challenge test result, nano-Zn>organic-Zn>ZnO>control; in regard to the gamma-globulin level, nano-Zn and organic-Zn>ZnO and control, with significant difference between groups. In the serum parameters aspect, serum Zn concentration in nano-Zn and organic-Zn groups were higher than in the ZnO and control groups, serum growth hormone concentration was increased in the nano-Zn group than in the other groups. In conclusion, nanosize zinc oxide for dietary supplementation can increase zinc digestibility, serum growth hormone levels and carbonic anhydrase activity and enhance the immune response of weanling piglets. PMID- 26805552 TI - Clinical and experimental role of ring finger protein 180 on lymph node metastasis and survival in gastric cancer. AB - BACKGROUND: The hypermethylation of ring finger protein (RNF) 180 DNA promoter is significantly associated with lymph node metastasis of gastric cancer. The present study explored the potential mechanism of RNF180-regulated lymph node metastasis of gastric cancer. METHODS: Associations between clinicopathological and survival data and RNF180 expression in gastric cancer tissues were analysed. The effects of RNF180 re-expression on gastric cancer cells were determined by means of proliferation, invasion, growth and lymphangiogenesis assays. A genome microarray was used to find potential target genes associated with lymphatic metastasis of gastric cancer cells regulated by RNF180. RESULTS: RNF180 was silenced or downregulated in 99 (73.9 per cent) of 134 gastric cancer tissues compared with 41.8 per cent of paired non-tumour tissues from patients. As an independent prognostic indicator of gastric cancer, RNF180 expression in gastric cancer tissues was negatively related to the number of metastatic lymph nodes. RNF180 was also downregulated in all seven gastric cancer cell lines examined. The re-expression of RNF180 in gastric cancer cells inhibited colony formation, proliferation, migration and invasion in vitro; re-expression of RNF180 also suppressed tumour growth and lymphangiogenesis in mice. Furthermore, re expression of RNF180 downregulated the expression of hepatocyte growth factor, matrix metalloproteinase (MMP) 2, MMP-14, vascular endothelial growth factor C/D and chemokine receptor 7 in gastric cancer cells; it also downregulated the expression of podoplanin in tumour tissue of nude mice. CONCLUSION: RNF180 appears to act as a suppressor gene that inhibits lymph node metastasis in gastric cancer. SURGICAL RELEVANCE: Biological mechanisms that lead to lymph node metastasis in gastric cancer have not been clarified. Ring finger protein (RNF) 180 has been shown to participate in the processes of lymph node metastasis in several human malignancies. In this study, silencing or downregulation of RNF180 expression was significantly associated with lymph node metastasis of gastric cancer. In vitro, RNF180 expression suppressed the common biological characteristics of gastric cancer cells (HGC-27), including proliferation, invasion, lymphangio genesis and chemotaxis. RNF180 expression also inhibited tumour growth and tumour lymphangiogenesis in vivo. These results show that RNF180 is capable of inhibiting lymph node metastasis of gastric cancer by suppressing the intracellular activation of malignant molecular signals. Therefore, RNF180 could be considered as a promising biomarker for evaluation of the tumour aggressiveness and may be a target for future therapeutic intervention. PMID- 26805554 TI - Long non-coding RNAs expression profiles in hepatocytes of mice after hematopoietic stem cell transplantation. AB - Hepatic veno-occlusive disease (HVOD), one serious complication following hematopoietic stem cell transplantation (HSCT), is mainly initiated by the damage to sinusoidal endothelial cells and hepatocytes. Long non-coding RNAs (lncRNAs) play an important role in the proliferation of hepatocytes and liver regeneration. lncRNAs profile in hepatocytes post-HSCT remains unclear. The aim of this study is to evaluate the profile of lncRNAs in hepatocytes of mice after HSCT. Mice HSCT model was established through infusion of 5 * 10(6) bone marrow mononuclear cells. On day 7, 14 and 33 after HSCT, mice were sacrificed for analysis of liver pathology, function and index. Total RNA was extracted from hepatocytes of mice on day 14 for microarray analysis of the expression profiles of lncRNAs by Arraystar Mouse lncRNA Microarray v2.0. Obvious edema and spotty necrosis of hepatocytes with inflammatory cells infiltration were observed post HSCT. Meanwhile, increased levels of alkaline phosphatase, aspartate transaminase, and total bilirubin, as well as elevated liver index were also found. 2,918 up-regulated and 1,911 down-regulated lncRNAs in hepatocytes were identified. Some of differentially expressed mRNAs had adjacent lncRNAs that were also significantly dysregulated, with the same dysregulation direction. T-cell receptor (up-regulation) and VEGF signaling pathway (down-regulation) were identified as one of the most enriched pathways. Dysregulated lncRNAs might be involved in hepatocytes damage after HSCT, suggesting targeting them might be a novel approach in amelioration of hepatocytes damage. PMID- 26805555 TI - Integrative analyses of leprosy susceptibility genes indicate a common autoimmune profile. AB - BACKGROUND: Leprosy is an ancient chronic infection in the skin and peripheral nerves caused by Mycobacterium leprae. The development of leprosy depends on genetic background and the immune status of the host. However, there is no systematic view focusing on the biological pathways, interaction networks and overall expression pattern of leprosy-related immune and genetic factors. OBJECTIVES: To identify the hub genes in the center of leprosy genetic network and to provide an insight into immune and genetic factors contributing to leprosy. METHODS: We retrieved all reported leprosy-related genes and performed integrative analyses covering gene expression profiling, pathway analysis, protein-protein interaction network, and evolutionary analyses. RESULTS: A list of 123 differentially expressed leprosy related genes, which were enriched in activation and regulation of immune response, was obtained in our analyses. Cross disorder analysis showed that the list of leprosy susceptibility genes was largely shared by typical autoimmune diseases such as lupus erythematosus and arthritis, suggesting that similar pathways might be affected in leprosy and autoimmune diseases. Protein-protein interaction (PPI) and positive selection analyses revealed a co-evolution network of leprosy risk genes. CONCLUSIONS: Our analyses showed that leprosy associated genes constituted a co-evolution network and might undergo positive selection driven by M. leprae. We suggested that leprosy may be a kind of autoimmune disease and the development of leprosy is a matter of defect or over-activation of body immunity. PMID- 26805556 TI - The effects of etanercept on replication, proliferation, survival, and apoptosis markers in moderate to severe psoriasis. PMID- 26805557 TI - The temporal structure of resting-state brain activity in the medial prefrontal cortex predicts self-consciousness. AB - Recent studies have demonstrated an overlap between the neural substrate of resting-state activity and self-related processing in the cortical midline structures (CMS). However, the neural and psychological mechanisms mediating this so-called "rest-self overlap" remain unclear. To investigate the neural mechanisms, we estimated the temporal structure of spontaneous/resting-state activity, e.g. its long-range temporal correlations or self-affinity across time as indexed by the power-law exponent (PLE). The PLE was obtained in resting-state activity in the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in 47 healthy subjects by functional magnetic resonance imaging (fMRI). We performed correlation analyses of the PLE and Revised Self Consciousness Scale (SCSR) scores, which enabled us to access different dimensions of self-consciousness and specified rest-self overlap in a psychological regard. The PLE in the MPFC's resting-state activity correlated with private self-consciousness scores from the SCSR. Conversely, we found no correlation between the PLE and the other subscales of the SCSR (public, social) or between other resting-state measures, including functional connectivity, and the SCSR subscales. This is the first evidence for the association between the scale-free dynamics of resting-state activity in the CMS and the private dimension of self-consciousness. This finding implies the relationship of especially the private dimension of self with the temporal structure of resting state activity. PMID- 26805559 TI - Increase in GFAP-positive astrocytes in histone demethylase GASC1/KDM4C/JMJD2C hypomorphic mutant mice. AB - GASC1, also known as KDM4C/JMJD2C, is a histone demethylase for histone H3 lysine 9 (H3K9) and H3K36. In this study, we observed an increase of GFAP-positive astrocytes in the brain of Gasc1 hypomorphic mutant mice at 2-3 months of age, but not at postnatal day 14 and day 30 by immunohistochemistry. Increases of GFAP positive astrocytes were widely observed in the forebrain and prominent in such regions as cerebral cortex, caudate putamen, amygdala and diencephalon, but not obvious in hippocampus. Taken together with our observations to be published elsewhere that Gasc1 hypomorphic mutant mice exhibit abnormal behaviors including hyperactivity, persistence and many types of learning and memory deficits and abnormal synaptic functions such as prolonged long-term potentiation, the increase in GFAP-positive astrocytes may help understand their phenotypes, because astrocytes are known to affect synaptic plasticity. PMID- 26805558 TI - Results of 20- versus 45-min post-infusion scalp cooling time in the prevention of docetaxel-induced alopecia. AB - PURPOSE: For patients, chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of treatment. Scalp cooling can prevent or minimise CIA; the results may depend on the duration of cooling. Since a previous study on post infusion cooling time in patients treated with docetaxel chemotherapy found no difference between 90 and 45 min, we investigated whether hair-preserving results could be maintained with a shorter post-infusion cooling time. METHODS: In this prospective, multi-centre randomised study, 134 patients who started treatment with docetaxel 75-100 mg/m(2) in a 3-weekly schedule were randomly assigned in a 1:1 ratio to a post-infusion cooling time of 45 or 20 min. The primary end point was the need for a wig or other head covering as assessed by the patient. A visual analogue scale (VAS) with a range from 0 (not tolerable) to 10 (very tolerable) was used to measure tolerance. RESULTS: Scalp cooling results were similar for 45- and 20-min post-infusion cooling times. Thirty-three out of 45 patients (73 %) treated with 20 min of post-infusion cooling did not need a form of head covering, compared with 41 out of 52 patients (79 %) treated with 45 min of post-infusion cooling (p = 0.5). The procedure was well tolerated (mean visual analogue score 8.3). Six patients stopped due to intolerance during the first treatment cycle. CONCLUSIONS: A 20-min post-infusion cooling time is effective and tolerable for patients treated with scalp cooling to prevent docetaxel induced alopecia. TRIAL REGISTRATION: Trialregister.nl Identifier, NTR 1856. PMID- 26805560 TI - Changes in beliefs and attitudes toward people with depression and schizophrenia results of a public campaign in Germany. AB - We examined the impact of a mental health awareness campaign on public attitudes. The campaign was embedded in the project psychenet - Hamburg Network for Mental Health. Beliefs and attitudes were examined before and after specific awareness measures in Hamburg (intervention region) and Munich (control region). Analyses were based on representative surveys (2011: N=2014; 2014: N=2006). Vignettes with symptoms suggestive of depression respectively schizophrenia were presented, followed by questions on social distance, beliefs and emotional reactions. Analyses of variance tested variations between regions over time and differences between those aware of the campaign and those not aware. In 2014, 7.3% (n=74) of the Hamburg respondents were aware of the psychenet campaign. Regarding the total sample, there were minor changes in attitudes. Differentiated according to campaign awareness among Hamburg respondents, those who were aware showed less desire for social distance toward a person with depression. Moreover, respondents aware of the campaign stated less often that a person with schizophrenia is in need of help. The campaign had small impact on attitudes. A substantial change in ingrained attitudes toward persons with mental health problems is difficult to achieve with interventions targeting the general public. PMID- 26805561 TI - Factors associated with overweight and obesity in schizophrenia, schizoaffective and bipolar disorders. AB - Evidence suggests abnormal bioenergetic status throughout the body in psychotic disorders. The present study examined predictors of elevated body mass index (BMI) across diagnostic categories of schizophrenia, schizoaffective and bipolar disorders. In a cross-sectional study, we studied demographic and clinical risk factors for overweight and obesity in a well-characterized sample of 262 inpatients and outpatients with schizophrenia (n=59), schizoaffective disorder (n=81) and bipolar I disorder (n=122). Across the three diagnostic categories, the prevalence of overweight (29.4%) and obesity (33.2%) combined was 62.6% (164/262). Logistic regression analyses, adjusted for age, sex and ethnicity, showed that schizoaffective disorder, lifetime major depressive episode, presence of prior suicide attempt, and more than 5 lifetime hospitalizations were significantly associated with BMI>=25. Patients with schizophrenia had significantly lower risk for overweight and obesity. Overall, we found that affective components of illness were associated with elevated BMI in our cross diagnostic sample. Our results show that patients with schizoaffective disorder have a greater risk for obesity. Identifying predictors of elevated BMI in patients with psychotic and mood disorders will help prevent obesity and related cardiovascular and cerebral complications. Future studies are needed to elucidate the mechanistic nature of the relationship between obesity and psychiatric illness. PMID- 26805563 TI - Platelet parameters (PLT, MPV, P-LCR) in patients with schizophrenia, unipolar depression and bipolar disorder. AB - There are no studies comparing platelet parameters platelet parameters (platelet count (PLT), mean platelet volume (MPV) and platelet large cell ratio (P-LCR)) between patients with schizophrenia, bipolar disorder and unipolar depression. Therefore, the aim of this study was to determine and compare differences in PLT, MPV and P-LCR in patients with schizophrenia, unipolar depression and bipolar disorder. This was a retrospective, cross-sectional, naturalistic study of 2377 patients (schizophrenia n=1243; unipolar depression n=791; bipolar disorder n=343, including bipolar depression n=259 and mania n=84). There were significant differences for PLT, MPV and P-LCR values between study groups. A significant percentage of patients with bipolar disorder had abnormal (too low or too high) number of platelets. Negative correlation between PLT and age was found in all study groups and positive correlation between age and MPV and P-LCR was found in patients with schizophrenia. PMID- 26805564 TI - Continuation and discontinuation of benzodiazepine prescriptions: A cohort study based on a large claims database in Japan. AB - Although benzodiazepines (BZDs) are often prescribed to treat a wide range of psychiatric and neurological conditions, they are also associated with various harms and risks including dependence. However the frequency of its continued use in the real world has not been well studied, especially at longer follow-ups. The aim of this study was to clarify the frequency of long-term BZD use among new BZD users over longer follow-ups and to identify its predictors. We conducted a cohort study to examine how frequently new BZD users became chronic users, based on a large claims database in Japan from January 2005 to June 2014. We used Cox proportional hazards models to identify potential predictors. A total 84,412 patients with new BZD prescriptions were included in our cohort. Among them, 35.8% continued to use BZD for three months, 15.2% for one year and 4.9% for eight years without ever attaining three months of no BZD prescription. The confirmed predictors for long-term BZD use were older age, psychiatrist prescriber, regular use, high dose of BZD, and concomitant prescription of psychotropic drugs. When we consider BZD use, we have to keep in mind these figures and avoid these predictors as much as possible. PMID- 26805562 TI - Treating Hoarding Disorder in a real-world setting: Results from the Mental Health Association of San Francisco. AB - Hoarding Disorder (HD) is associated with substantial distress, impairment, and individual and societal costs. Cognitive-behavioral therapy (CBT) tailored to HD is the best-studied form of treatment and can be led by mental health professionals or by non-professionals (peers) with specific training. No previous study has directly compared outcomes for therapist-led and peer-led groups, and none have examined the effectiveness of these groups in a real-world setting. We used retrospective data to compare psychologist-led CBT groups (G-CBT) to groups led by peer facilitators using the Buried in Treasures workbooks (G-BiT) in individuals who sought treatment for HD from the Mental Health Association of San Francisco. The primary outcome was change in Hoarding Severity Scale scores. Approximate costs per participant were also examined. Both G-CBT and G-BiT showed improvement consistent with previous reports (22% improvement overall). After controlling for baseline group characteristics, there were no significant differences in outcomes between G-CBT and G-BiT. For G-CBT, where additional outcome data were available, functional impairment and severity of hoarding symptoms improved to a similar degree as compared to previous G-CBT studies, while hoarding-related cognition improved to a lesser degree (also consistent with previous studies). G-BiT cost approximately $100 less per participant than did G-CBT. PMID- 26805565 TI - Profiling the psychotic, depressive and anxiety symptoms in chronic ketamine users. AB - OBJECTIVE: Although concern about chronic ketamine abuse has grown, the characteristic symptomatology of chronic ketamine users has yet to be examined. This study aims to measure the psychotic, depressive and anxiety symptoms in chronic ketamine users. METHODS: A group of chronic ketamine users in Guangzhou, China were evaluated. The socio-demographic and drug use characteristics of subjects were documented. Symptoms of psychosis, depression, anxiety were evaluated by the Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). The severity of the symptoms was identified by standard severity cutoffs. RESULTS: The PANSS total score, positive symptom, negative symptom, general psychopathology subscale score were 45.3+/-8.4, 8.0+/-1.7, 13.2+/- 3.9 and 24.2+/- 4.9 respectively. BDI and BAI score was 13.1+/-6.5 and 15.7+/-9.6 respectively. 77.5% and 46.0% of the subjects showed moderate to severe depressive symptoms and anxiety symptoms respectively. The BDI score was positively correlated with ketamine use frequency. The BAI score was positively correlated with ketamine use frequency. CONCLUSIONS: Depressive symptoms were commonly presented in chronic ketamine users. The higher ketamine use frequency and dosage were associated with more severe depressive symptoms. PMID- 26805566 TI - Sleep patterns as a predictor for length of stay in a psychiatric intensive care unit. AB - Systematic evaluations of the relationship between sleep patterns and length of stay in psychiatric intensive care units (PICUs) are lacking. The aims of the present study were to explore if sleep duration or night-to-night variations in sleep duration the first nights predict length of stay in a PICU. Consecutive patients admitted to a PICU were included (N=135) and the nurses registered the time patients were observed sleeping. In the three first nights, the mean sleep duration was 7.5 (+/-3.2)h. Sleep duration the first night correlated negatively with the length of stay for patients with schizophrenia. The mean difference in sleep duration from night one to night two were 3.3 (+/-3.0)h and correlated with length of stay for the whole group of patients, but especially for patients with schizophrenia. Patients of all diagnostic groups admitted to a PICU had pronounced intra-individual night-to-night variations in sleep duration. Stabilizing night-to-night variations of sleep duration might be a major goal in treatment. PMID- 26805568 TI - Outcomes of liver resection for haemorrhagic hepatocellular adenoma. AB - BACKGROUND: Intratumoral bleeding and/or intraperitoneal rupture occurs in up to 20% of patients with hepatocellular adenoma (HCA). Hepatectomy in the presence of haemorrhagic HCA has been associated with increased morbidity and mortality rates. This study evaluates the outcomes of hepatectomy for haemorrhagic HCA at a single institution. METHODS: Between January 1997 and December 2012, 52 consecutive patients underwent liver resection for HCA. Among them, 14 patients were resected for haemorrhagic (H)-HCAs (including 9 cases of intratumoural bleeding and 5 cases of intraperitoneal bleeding) and 38 for non-haemorrhagic (NH)-HCAs. RESULTS: The preoperative characteristics were similar between the two groups except for younger age (p = .001) and shorter duration of hormonal use (p = .001) in (H)-HCAs. There were no mortalities. Intraoperative blood loss, transfusion rate, and postoperative morbidity were comparable between the two groups of patients (p = ns). The length of hospital stay was significantly longer in (H)-HCAs (p = .03). In all the resected H-HCAs, pathology showed central haemorrhagic changes with tumoral cells at the periphery of the lesions. CONCLUSIONS: Liver resection for H- and NH-HCAs can be achieved with no mortality and comparable short-term outcomes. PMID- 26805569 TI - Percutaneous endoscopic lumbar discectomy for recurrent lumbar disc herniation. AB - The objective of this systematic review was to identify the effectiveness of percutaneous endoscopic lumbar discectomy (PELD) in the treatment of recurrent lumbar disc herniation (rLDH) and to present its indications and techniques. We conducted a comprehensive search in MEDLINE, EMBASE, PubMed, Web of Science and Cochrane databases, searching for relevant studies of managing rLDH with PELD up to July 2015. Only papers published in English were included. Two review authors independently selected the studies, extracted relevant data and assessed their methodological quality. The Cochrane Collaboration's Revman 5.3 software was used for data analyses among the controlled studies. At last, one randomized controlled trial (RCT), two non-randomized control studies and five observational studies including a total of 579 cases were selected for this system review. The methodological quality of these studies was low to modern. The mean overall improvement of leg pain (visual analogue scale) was 66.92% (50.6%-89.87%), back pain (visual analogue scale) 54.91% (29%-67.95%), Oswestry Disability Index 60.9% (40.7%-75%), global perceived effect (MacNab/other) 75.77% (60%-95%). The mean overall of complication rate was 4.89% (0%-9.76%), dural tear rate 0.1% (0% 4.9%), recurrence rate 6.3% (4%-10%), re-operation rate 3.66% (2.33%-4.8%). We conducted a meta-analysis among the control trials. Compared with Open discectomy (OD), PELD resulted in better outcomes in terms of operative time, blood loss, lower complication rates, but with no significance differences regarding hospital stay, second recurrence rate, Macnab criteria and pain reduction. In conclusion, according to the current evidence, PELD is an effective procedure for the treatment of rLDH in terms of reducing complication and shorting hospital course, comparing with OD. Therefore, we suggested that PELD was a feasible alternative to OD in the treatment of the rLDH in the condition of proper indication. High quality RCTs with large sample sizes are needed to further confirm these results. PMID- 26805570 TI - Short- and long-term outcomes of laparoscopic surgery for colorectal cancer in the elderly: A prospective cohort study. AB - BACKGROUND: The aim of this study was to evaluate the safety and validity of laparoscopic colorectal surgery for elderly patients. We compared the short and long-term postoperative outcomes of laparoscopic colorectal surgery in patients aged >=75 years (elderly patients; EP) and <75 years (relatively younger patients; RP). METHODS: Clinicopathological data and short- and long-term outcomes after laparoscopic surgery for colorectal cancer were compared between the EP (n = 53) and RP groups (n = 155). RESULTS: In the EP group, patients with American Society of Anesthesiologists score II (p = 0.047) and medical comorbidity rate (EP vs RP: 83.0% vs 56.8%, p < 0.001), especially for cardiovascular disease (64.2% vs 37.5%, p < 0.001) and diabetes mellitus (20.8% vs 9.7%, p = 0.044), were significantly higher than those in the RP group. Regarding the clinical characteristics, the ratio of right colectomy (50.9% vs 25.3%, p < 0.001) and pathological tumor grade T4 (18.9% vs 7.7%, p = 0.044) were significantly higher in the EP group. There was no significant difference in the variation of pathological stage between the two groups. In the postoperative course, there were no significant differences regarding short-term postoperative outcomes between the EP and RP groups, including that for timing of oral diet tolerance (3.9 days vs 3.5 days, p = 0.073), first flatus (2.3 days vs 2.0 days, p = 0.636), first bowel movement (3.3 days vs 3.7 days, p = 0.153), ambulation after surgery (1.7 days vs 1.5 days, p = 0.081), postoperative hospital stay (10.5 days vs 10.8 days, p = 0.469), and incidence of postoperative complications (20.8% vs 15.5%, p = 0.385), respectively. Regarding the long-term outcomes, there were no significant differences in recurrence-free survival (RFS) (5-year RFS, 74.0% vs 85.2%, p = 0.091) and overall survival (OS) (5-year OS, 81.8% vs 90.1%, p = 0.112) between the two groups. CONCLUSION: Laparoscopic colorectal surgery in elderly patients was safe and well-tolerated in comparison with the relatively younger patients. PMID- 26805571 TI - Segment coupling and coordination variability analyses of the roundhouse kick in taekwondo relative to the initial stance position. AB - The initial stance position (ISP) has been observed as a factor affecting the execution technique during taekwondo kicks. In the present study, authors aimed to analyse a roundhouse kick to the chest by measuring movement coordination and the variability of coordination and comparing this across the different ISP (0 degrees , 45 degrees and 90 degrees ). Eight experienced taekwondo athletes performed consecutive kicking trials in random order from every of the three relative positions. The execution was divided into three phases (stance, first swing and second swing phase). A motion capture system was used to measure athletes' angular displacement of pelvis and thigh. A modified vector coding technique was used to quantify the coordination of the segments which contributed to the overall movement. The variability of this coordination (CV) for each ISP was also calculated. Comparative analysis showed that during the stance phase in the transverse plane, athletes coordinated movement of the trunk and thigh with a higher frequency of in-phase and lower frequency of exclusive thigh rotation in the 0 degrees stance than the 90 degrees stance position (P < 0.05). CV was also influenced by the different ISP. During the first swing and the majority of the second swing phase, predominant in-phase coordination of the pelvis and thigh was observed. Including exercises that require in-phase movement could not only help athletes to acquire coordination stability but also efficiency. The existence of a constraint such as ISP implies an increase of the variability when the athletes have to kick from ISP they are not used to adopt (i.e., 0 degrees and 90 degrees ISP) as an evidence of adaptability in the athletes' execution technique. PMID- 26805572 TI - Alterations in oxidative, inflammatory and apoptotic events in short-lived and long-lived mice testes. AB - Aged testes undergo profound histological and morphological alterations leading to a reduced functionality. Here, we investigated whether variations in longevity affect the development of local inflammatory processes, the oxidative state and the occurrence of apoptotic events in the testis. To this aim, well-established mouse models with delayed (growth hormone releasing hormone-knockout and Ames dwarf mice) or accelerated (growth hormone-transgenic mice) aging were used. We hereby show that the testes of short-lived mice show a significant increase in cyclooxygenase 2 expression, PGD2 production, lipid peroxidation, antioxidant enzymes expression, local macrophages and TUNEL-positive germ cells numbers, and the levels of both pro-caspase-3 and cleaved caspase-3. In contrast, although the expression of antioxidant enzymes remained unchanged in testes of long-lived mice, the remainder of the parameters assessed showed a significant reduction. This study provides novel evidence that longevity confers anti-inflammatory, anti oxidant and anti-apoptotic capacities to the adult testis. Oppositely, short lived mice suffer testicular inflammatory, oxidative and apoptotic processes. PMID- 26805573 TI - Crystal Structures and Inhibition Kinetics Reveal a Two-Stage Catalytic Mechanism with Drug Design Implications for Rhomboid Proteolysis. AB - Intramembrane proteases signal by releasing proteins from the membrane, but despite their importance, their enzymatic mechanisms remain obscure. We probed rhomboid proteases with reversible, mechanism-based inhibitors that allow precise kinetic analysis and faithfully mimic the transition state structurally. Unexpectedly, inhibition by peptide aldehydes is non-competitive, revealing that in the Michaelis complex, substrate does not contact the catalytic center. Structural analysis in a membrane revealed that all extracellular loops of rhomboid make stabilizing interactions with substrate, but mainly through backbone interactions, explaining rhomboid's broad sequence selectivity. At the catalytic site, the tetrahedral intermediate lies covalently attached to the catalytic serine alone, with the oxyanion stabilized by unusual tripartite interactions with the side chains of H150, N154, and the backbone of S201. We also visualized unexpected substrate-enzyme interactions at the non-essential P2/P3 residues. These "extra" interactions foster potent rhomboid inhibition in living cells, thereby opening avenues for rational design of selective rhomboid inhibitors. PMID- 26805574 TI - A 3' UTR-Derived Small RNA Provides the Regulatory Noncoding Arm of the Inner Membrane Stress Response. AB - Small RNAs (sRNAs) from conserved noncoding genes are crucial regulators in bacterial signaling pathways but have remained elusive in the Cpx response to inner membrane stress. Here we report that an alternative biogenesis pathway releasing the conserved mRNA 3' UTR of stress chaperone CpxP as an ~60-nt sRNA provides the noncoding arm of the Cpx response. This so-called CpxQ sRNA, generated by general mRNA decay through RNase E, acts as an Hfq-dependent repressor of multiple mRNAs encoding extracytoplasmic proteins. Both CpxQ and the Cpx pathway are required for cell survival under conditions of dissipation of membrane potential. Our discovery of CpxQ illustrates how the conversion of a transcribed 3' UTR into an sRNA doubles the output of a single mRNA to produce two factors with spatially segregated functions during inner membrane stress: a chaperone that targets problematic proteins in the periplasm and a regulatory RNA that dampens their synthesis in the cytosol. PMID- 26805575 TI - Nonsense-Mediated Decay Restricts LncRNA Levels in Yeast Unless Blocked by Double Stranded RNA Structure. AB - Antisense long non-coding (aslnc)RNAs represent a substantial part of eukaryotic transcriptomes that are, in yeast, controlled by the Xrn1 exonuclease. Nonsense Mediated Decay (NMD) destabilizes the Xrn1-sensitive aslncRNAs (XUT), but what determines their sensitivity remains unclear. We report that 3' single-stranded (3'-ss) extension mediates XUTs degradation by NMD, assisted by the Mtr4 and Dbp2 helicases. Single-gene investigation, genome-wide RNA analyses, and double stranded (ds)RNA mapping revealed that 3'-ss extensions discriminate the NMD targeted XUTs from stable lncRNAs. Ribosome profiling showed that XUT are translated, locking them for NMD activity. Interestingly, mutants of the Mtr4 and Dbp2 helicases accumulated XUTs, suggesting that dsRNA unwinding is a critical step for degradation. Indeed, expression of anticomplementary transcripts protects cryptic intergenic lncRNAs from NMD. Our results indicate that aslncRNAs form dsRNA that are only translated and targeted to NMD if dissociated by Mtr4 and Dbp2. We propose that NMD buffers genome expression by discarding pervasive regulatory transcripts. PMID- 26805576 TI - Hevea brasiliensis prohevein possesses a conserved C-terminal domain with amyloid like properties in vitro. AB - Prohevein is a wound-induced protein and a main allergen from latex of Hevea brasiliensis (rubber tree). This 187 amino-acid protein is cleaved in two fragments: a N-terminal 43 amino-acids called hevein, a lectin bearing a chitin binding motif with antifungal properties and a C-terminal domain (C-ter) far less characterized. We provide here new insights on the characteristics of prohevein, hevein and C-terminal domain. Using complementary biochemical (ThT/CR/chitin binding, agglutination) and structural (modeling, ATR-FTIR, TEM, WAXS) approaches, we show that this domain clearly displays all the characteristics of an amyloid-like proteins in vitro, that could confer agglutination activity in synergy with its chitin-binding activity. Additionally, this C-ter domain is highly conserved and present in numerous plant prohevein-like proteins or pathogenesis-related (PR and WIN) proteins. This could be the hallmark of the eventual presence of proteins with amyloid properties in plants, that could potentially play a role in defense through aggregation properties. PMID- 26805577 TI - The effect of crystallinity on photocatalytic performance of Co3O4 water splitting cocatalysts. AB - Cocatalysts, when loaded onto a water splitting photocatalyst, accelerate the gas evolution reaction and improve the efficiency of the photocatalyst. In this paper, we report that the efficiency of the photocatalyst is enhanced using an amorphous cobalt oxide cocatalyst. The WO3 film, when loaded with amorphous or nanocrystalline Co3O4, shows an improvement of up to 40% in photocurrent generation and 34% in hydrogen gas evolution. The effect of cocatalyst crystallinity on performance was systematically studied, and we found that the photocurrent deteriorates with the conversion of the cocatalyst to a highly crystalline phase at an annealing temperature of 500 degrees C. The mechanism of this effect was studied in detail using electrochemical impedance spectroscopy, and the enhancement effect produced by the amorphous cocatalyst is attributed to the large density of unsaturated catalytically active sites in the amorphous material. PMID- 26805578 TI - Scavenging of nitric oxide by hemoglobin in the tunica media of porcine coronary arteries. AB - Scavenging of nitric oxide (NO) often interferes with studies on NO signaling in cell-free preparations. We observed that formation of cGMP by NO-stimulated purified soluble guanylate cyclase (sGC) was virtually abolished in the presence of cytosolic preparations of porcine coronary arteries, with the scavenging activity localized in the tunica media (smooth muscle layer). Electrochemical measurement of NO release from a donor compound and light absorbance spectroscopy showed that cytosolic preparations contained a reduced heme protein that scavenged NO. This protein, which reacted with anti-human hemoglobin antibodies, was efficiently removed from the preparations by haptoglobin affinity chromatography. The cleared cytosols showed only minor scavenging of NO according to electrochemical measurements and did not decrease cGMP formation by NO stimulated sGC. In contrast, the column flow-through caused a nearly 2-fold increase of maximal sGC activity (from 33.1 +/- 1.6 to 54.9 +/- 2.2 MUmol * min( 1) * mg(-1)). The proteins retained on the affinity column were identified as hemoglobin alpha and beta subunits. The results indicate that hemoglobin, presumably derived from vasa vasorum erythrocytes, is present and scavenges NO in preparations of porcine coronary artery smooth muscle. Selective removal of hemoglobin-mediated scavenging unmasked stimulation of maximal NO-stimulated sGC activity by a soluble factor expressed in vascular tissue. PMID- 26805579 TI - Antibiograms in five pipetting steps: precise dilution assays in sub-microliter volumes with a conventional pipette. AB - We demonstrate a standalone microfluidic chip that allows us to carry out commonly executed antibiotic susceptibility assays in an array of nanoliter droplets. We eliminated the need for automation in performing an exemplary complicated liquid handling assay on a chip. Operations on droplets are hard wired into the microfluidic chip. The liquid handling protocol can be executed with a simple and commonly available source of flow such as an automatic manual pipette. The system passively prepares a series of dilutions of a chemical compound and mixes them with portions of the sample. The precision of metering, merging, mixing, and splitting of discrete portions of liquid samples is rooted in the passive capillary action in microfluidic traps and not in the precision of dosing with a pipette. We show an exemplary use of the device in the determination of the minimum inhibitory concentration (MIC) of ampicillin against E. coli ATCC 25922. PMID- 26805580 TI - Characterization and expression of soluble guanylate cyclase in skins and melanocytes of sheep. AB - The study reported the characterization of soluble guanylate cyclase (sGC) with the size of CDS of 1860bp, encoding a protein of 620 amino acids and containing several conserved functional domains including HNOB, HNOBA, and CHD. Quantitative real time PCR analysis of sGC showed that the expression of sGC mRNA is higher (~5 fold) in white sheep skin relative to black sheep skin with significant difference (P<0.01). Using a rabbit polyclonal anti-sGC antibody, an immune reactive band corresponding to sheep sGC protein was detected in the skin samples by Western blotting analysis, and the expression of sGC protein was significantly higher in white sheep skin compared to black sheep skin (P<0.01). Immunohistochemical analysis revealed that sGC protein was localized in cytoplasm and intercellular substance of upper hair papilla in hair follicles of white sheep skin, but the protein was localized in cytoplasm and intercellular substance of lower hair bulb and outer root sheath cells in hair follicles of black sheep skin. The immunocytochemical analysis revealed that sGC was expressed in melanocytes in vitro of sheep skin. Over expression of sGC in melanocytes resulted in decreased expression of key melanogenic genes including microphthalmia transcription factor (MITF), tyrosinase (TYR), tyrosinase related protein 1(TYRTP1), and tyrosinase related protein 2(TYRP2) both at mRNA and protein level. Moreover, the melanocytes was capable of producing cGMP and cAMP. The observed differential expression and localization of sGC in sheep skins and melanocytes and the capability of producing cGMP and cAMP, which suggested a potential role for this gene in hair color regulation. PMID- 26805581 TI - Tropomyosin-1 protects transformed alveolar epithelial cells against cigaret smoke extract through the stabilization of F-actin-dependent cell-cell junctions. AB - The aim of the study was to estimate the effect of tropomyosin-1-based structural stabilization of F-actin in transformed human alveolar epithelial line H1299 cells subjected to high oxidative stress induced by cigaret smoke extract. We demonstrated here that cigaret smoke extract induces cell shrinking and detachment as a consequence of F-actin cytoskeleton degradation in H1299 cells not overexpressing tropomyosin-1. Furthermore, the treatment of these cells with cigaret smoke extract resulted in the loss of peripheral localization of ZO-1 and initiated apoptosis. In contrast, structural stabilization of F-actin, by overexpression of tropomyosin-1, preserved cell to cell interactions through the attenuation of cortical actin organization into thin fibers and thus protected these cells against oxidative stress-induced degradation of actin cytoskeleton and cell death. In conclusion, we suggest that structural stabilization of thin cortical F-actin fibers increases link between tight junctions proteins and actin cytoskeleton and thus protects H1299 cells against cigaret smoke extract. PMID- 26805582 TI - Aberrant Cross-Brain Network Interaction in Children With Attention Deficit/Hyperactivity Disorder and Its Relation to Attention Deficits: A Multisite and Cross-Site Replication Study. AB - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is increasingly viewed as a disorder stemming from disturbances in large-scale brain networks, yet the exact nature of these impairments in affected children is poorly understood. We investigated a saliency-based triple-network model and tested the hypothesis that cross-network interactions between the salience network (SN), central executive network, and default mode network are dysregulated in children with ADHD. We also determined whether network dysregulation measures can differentiate children with ADHD from control subjects across multisite datasets and predict clinical symptoms. METHODS: Functional magnetic resonance imaging data from 180 children with ADHD and control subjects from three sites in the ADHD-200 database were selected using case-control design. We investigated between-group differences in resource allocation index (RAI) (a measure of SN centered triple network interactions), relation between RAI and ADHD symptoms, and performance of multivariate classifiers built to differentiate children with ADHD from control subjects. RESULTS: RAI was significantly lower in children with ADHD than in control subjects. Severity of inattention symptoms was correlated with RAI. Remarkably, these findings were replicated in three independent datasets. Multivariate classifiers based on cross-network coupling measures differentiated children with ADHD from control subjects with high classification rates (72% to 83%) for each dataset. A novel cross-site classifier based on training data from one site accurately (62% to 82%) differentiated children with ADHD on test data from the two other sites. CONCLUSIONS: Aberrant cross-network interactions between SN, central executive network, and default mode network are a reproducible feature of childhood ADHD. The triple-network model provides a novel, replicable, and parsimonious systems neuroscience framework for characterizing childhood ADHD and predicting clinical symptoms in affected children. PMID- 26805584 TI - FKBP5 Messenger RNA Increases After Adolescence in Human Dorsolateral Prefrontal Cortex. PMID- 26805583 TI - Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate. AB - BACKGROUND: Inherited differences in the rate of metabolism of nicotine, the addictive chemical in tobacco, affect smoking behavior and quitting success. The nicotine metabolite ratio (3'-hydroxycotinine/cotinine) is a reliable measure of nicotine clearance and a well-validated predictive biomarker of response to pharmacotherapy. To clarify the mechanisms underlying these associations, we investigated the neural responses to smoking cues in normal and slow nicotine metabolizers. METHODS: Treatment-seeking smokers (N = 69; 30 slow metabolizers and 39 normal metabolizers) completed a visual cue reactivity task during functional magnetic resonance imaging on two separate occasions: once during smoking satiety and once after 24 hours of smoking abstinence. RESULTS: In whole brain analysis, normal (compared with slow) metabolizers exhibited heightened abstinence-induced neural responses to smoking cues in the left caudate, left inferior frontal gyrus, and left frontal pole. These effects were more pronounced when extreme groups of slow and normal metabolizers were examined. Greater activation in the left caudate and left frontal pole was associated with abstinence-induced subjective cravings to smoke. CONCLUSIONS: Inherited differences in rate of nicotine elimination may drive neural responses to smoking cues during early abstinence, providing a plausible mechanism to explain differences in smoking behaviors and response to cessation treatment. Normal metabolizers may benefit from adjunctive behavioral smoking cessation treatments, such as cue exposure therapy. PMID- 26805585 TI - Reaching Millennium Development Goal 4. PMID- 26805586 TI - Malawi and Millennium Development Goal 4: a Countdown to 2015 country case study. AB - BACKGROUND: Several years in advance of the 2015 endpoint for the Millennium Development Goals (MDGs), Malawi was already thought to be one of the few countries in sub-Saharan Africa likely to meet the MDG 4 target of reducing under 5 mortality by two-thirds between 1990 and 2015. Countdown to 2015 therefore selected the Malawi National Statistical Office to lead an in-depth country case study, aimed mainly at explaining the country's success in improving child survival. METHODS: We estimated child and neonatal mortality for the years 2000 14 using five district-representative household surveys. The study included recalculation of coverage indicators for that period, and used the Lives Saved Tool (LiST) to attribute the child lives saved in the years from 2000 to 2013 to various interventions. We documented the adoption and implementation of policies and programmes affecting the health of women and children, and developed estimates of financing. FINDINGS: The estimated mortality rate in children younger than 5 years declined substantially in the study period, from 247 deaths (90% CI 234-262) per 1000 livebirths in 1990 to 71 deaths (58-83) in 2013, with an annual rate of decline of 5.4%. The most rapid mortality decline occurred in the 1-59 months age group; neonatal mortality declined more slowly (from 50 to 23 deaths per 1000 livebirths), representing an annual rate of decline of 3.3%. Nearly half of the coverage indicators have increased by more than 20 percentage points between 2000 and 2014. Results from the LiST analysis show that about 280,000 children's lives were saved between 2000 and 2013, attributable to interventions including treatment for diarrhoea, pneumonia, and malaria (23%), insecticide-treated bednets (20%), vaccines (17%), reductions in wasting (11%) and stunting (9%), facility birth care (7%), and prevention and treatment of HIV (7%). The amount of funding allocated to the health sector has increased substantially, particularly to child health and HIV and from external sources, but remains below internationally agreed targets. Key policies to address the major causes of child mortality and deliver high-impact interventions at scale throughout Malawi began in the late 1990s and intensified in the latter half of the 2000s and into the 2010s, backed by health-sector-wide policies to improve women's and children's health. INTERPRETATION: This case study confirmed that Malawi had achieved MDG 4 for child survival by 2013. Our findings suggest that this was achieved mainly through the scale-up of interventions that are effective against the major causes of child deaths (malaria, pneumonia, and diarrhoea), programmes to reduce child undernutrition and mother-to-child transmission of HIV, and some improvements in the quality of care provided around birth. The Government of Malawi was among the first in sub-Saharan Africa to adopt evidence based policies and implement programmes at scale to prevent unnecessary child deaths. Much remains to be done, building on this success and extending it to higher proportions of the population and targeting continued high neonatal mortality rates. FUNDING: Bill & Melinda Gates Foundation, WHO, The World Bank, Government of Australia, Government of Canada, Government of Norway, Government of Sweden, Government of the UK, and UNICEF. PMID- 26805587 TI - "Alert and Oriented * 3?" Correlates of Mini-Cog Performance in a Post/Nondelirious Intensive Care Unit Sample. AB - BACKGROUND: Cognitive impairment has been found to be a predictor of adverse medical outcomes, including nonadherence, recurrent medical crises resulting in early readmissions, and death. OBJECTIVE: The Mini-Cog has been proposed for bedside/clinic cognitive testing. Its validity as a measure of central nervous system (CNS) impairment has never been tested against measures of CNS-medical history, CNS scans, selected laboratory findings, observed in-hospital nondelirious memory impairment, or collateral history from family. METHODS: We observed Mini-Cog performance in 107 post/nondelirious medical intensive care unit patients and tested its association with age, CNS-medical history, CNS scans, selected laboratory findings, and behavioral history (in-hospital observation of memory problems and collateral history from family or significant others). RESULTS: The overall Mini-Cog covaried with age, various measures of CNS impairment, abnormal laboratory findings, and measures of preadmission "forgetfulness" per family and by in-hospital staff observation. Unique variance in predicting overall Mini-Cog scores included age, positive CNS scan, and behavioral history. Of 91 patients found to be "alert and oriented * 3," 76% were impaired in immediate memory, short-term memory, or clock drawing. CONCLUSIONS: The Mini-Cog appears to be a brief, yet valid, measure of CNS dysfunction that significantly enhances sensitivity of evaluation at the bedside. Failure to evaluate patients with a formal examination like the Mini-Cog appears to miss up to 76% of patients with moderate cognitive impairment. PMID- 26805588 TI - Depressive Symptoms Before, During, and After Delirium: A Literature Review. AB - BACKGROUND: Delirium and depression are often thought of as mutually exclusive conditions. However, several studies cite depression as a risk factor for delirium whereas others note that patients with delirium often manifest depressive symptoms. Whether these depressive symptoms persist after delirium resolves remains unclear. OBJECTIVES: This article reviews published studies that have investigated the relationship between depression and delirium. METHODS: Literature searches on PubMed, CINAHL, Cochrane Library, and PsycInfo were conducted using search criteria "delirium" AND "depress*" as keywords or MeSH terms. RESULTS: Of 722 search results, 10 prospective cohort studies were identified for inclusion. These studies were categorized regarding the time of assessment for depressive symptoms. Included studies varied greatly (regarding their index population, their methods of assessment, and their timing of assessments). Of the studies, 3 involved patients undergoing hip fracture repair. They demonstrated more severe depressive symptoms both during delirium and after delirium ended. Conversely, the other studies did not find any statistically significant correlations between the 2 conditions. CONCLUSIONS: The literature suggests a correlation between depression and delirium in patients with hip fracture. Whether other specific populations have higher comorbidity is unclear. Unfortunately, studies varied widely in their methods, precluding a meta analysis. Nonetheless, our review provides a foundation for future research. PMID- 26805591 TI - Boosting spin-caloritronic effects by attractive correlations in molecular junctions. AB - In nanoscopic systems quantum confinement and interference can lead to an enhancement of thermoelectric properties as compared to conventional bulk materials. For nanostructures, such as molecules or quantum dots coupled to external leads, the thermoelectric figure of merit can reach or even exceed unity. Moreover, in the presence of external magnetic field or when the leads are ferromagnetic, an applied temperature gradient can generate a spin voltage and an associated spin current flow in the system, which makes such nanostructures particularly interesting for future thermoelectric applications. In this study, by using the numerical renormalization group method, we examine the spin dependent thermoelectric transport properties of a molecular junction involving an orbital level with attractive Coulomb correlations coupled to ferromagnetic leads. We analyze how attractive correlations affect the spin-resolved transport properties of the system and find a nontrivial dependence of the conductance and tunnel magnetoresistance on the strength and sign of those correlations. We also demonstrate that attractive correlations can lead to an enhancement of the spin thermopower and the figure of merit, which can be controlled by a gate voltage. PMID- 26805589 TI - Structural Insights into the Quaternary Catalytic Mechanism of Hexameric Human Quinolinate Phosphoribosyltransferase, a Key Enzyme in de novo NAD Biosynthesis. AB - Quinolinate phosphoribosyltransferase (QPRT) catalyses the production of nicotinic acid mononucleotide, a precursor of de novo biosynthesis of the ubiquitous coenzyme nicotinamide adenine dinucleotide. QPRT is also essential for maintaining the homeostasis of quinolinic acid in the brain, a possible neurotoxin causing various neurodegenerative diseases. Although QPRT has been extensively analysed, the molecular basis of the reaction catalysed by human QPRT remains unclear. Here, we present the crystal structures of hexameric human QPRT in the apo form and its complexes with reactant or product. We found that the interaction between dimeric subunits was dramatically altered during the reaction process by conformational changes of two flexible loops in the active site at the dimer-dimer interface. In addition, the N-terminal short helix alpha1 was identified as a critical hexamer stabilizer. The structural features, size distribution, heat aggregation and ITC studies of the full-length enzyme and the enzyme lacking helix alpha1 strongly suggest that human QPRT acts as a hexamer for cooperative reactant binding via three dimeric subunits and maintaining stability. Based on our comparison of human QPRT structures in the apo and complex forms, we propose a drug design strategy targeting malignant glioma. PMID- 26805590 TI - Functional connectivity based parcellation of the human medial temporal lobe. AB - Regional differences in large-scale connectivity have been proposed to underlie functional specialization along the anterior-posterior axis of the medial temporal lobe (MTL), including the hippocampus (HC) and the parahippocampal gyrus (PHG). However, it is unknown whether functional connectivity (FC) can be used reliably to parcellate the human MTL. The current study aimed to differentiate subregions of the HC and the PHG based on patterns of whole-brain intrinsic FC. FC maps were calculated for each slice along the longitudinal axis of the PHG and the HC. A hierarchical clustering algorithm was then applied to these data in order to group slices according to the similarity of their connectivity patterns. Surprisingly, three discrete clusters were identified in the PHG. Two clusters corresponded to the parahippocampal cortex (PHC) and the perirhinal cortex (PRC), and these regions showed preferential connectivity with previously described posterior-medial and anterior-temporal networks, respectively. The third cluster corresponded to an anterior PRC region previously described as area 36d, and this region exhibited preferential connectivity with auditory cortical areas and with a network involved in visceral processing. The three PHG clusters showed different profiles of activation during a memory-encoding task, demonstrating that the FC-based parcellation identified functionally dissociable sub-regions of the PHG. In the hippocampus, no sub-regions were identified via the parcellation procedure. These results indicate that connectivity-based methods can be used to parcellate functional regions within the MTL, and they suggest that studies of memory and high-level cognition need to differentiate between PHC, posterior PRC, and anterior PRC. PMID- 26805592 TI - Emergency Care Use and the Medicare Hospice Benefit for Individuals with Cancer with a Poor Prognosis. AB - OBJECTIVES: To compare patterns of emergency department (ED) use and inpatient admission rates for elderly adults with cancer with a poor prognosis who enrolled in hospice to those of similar individuals who did not. DESIGN: Matched case control study. SETTING: Nationally representative sample of Medicare fee-for service beneficiaries with cancer with a poor prognosis who died in 2011. PARTICIPANTS: Beneficiaries in hospice matched to individuals not in hospice on time from diagnosis of cancer with a poor prognosis to death, region, age, and sex. MEASUREMENTS: Comparison of ED use and inpatient admission rates before and after hospice enrollment for beneficiaries in hospice and controls. RESULTS: Of 272,832 matched beneficiaries, 81% visited the ED in the last 6 months of life. At baseline, daily ED use and admission rates were not significantly different between beneficiaries in and not in hospice. By the week before death, nonhospice controls averaged 69.6 ED visits/1,000 beneficiary-days, versus 7.6 for beneficiaries in hospice (rate ratio (RR) = 9.7, 95% confidence interval (CI) = 9.3-10.0). Inpatient admission rates in the last week of life were 63% for nonhospice controls and 42% for beneficiaries in hospice (RR = 1.51, 95% CI = 1.45-1.57). Of all beneficiaries in hospice, 28% enrolled during inpatient stays originating in EDs; they accounted for 35.7% (95% CI = 35.4-36.0%) of all hospice stays of less than 1 month and 13.9% (95% CI = 13.6-14.2%) of stays longer than 1 month. CONCLUSION: Most Medicare beneficiaries with cancer with a poor prognosis visited EDs at the end of life. Hospice enrollment was associated with lower ED use and admission rates. Many individuals enrolled in hospice during inpatient stays that followed ED visits, a phenomenon linked to shorter hospice stays. These findings must be interpreted carefully given potential unmeasured confounders in matching. PMID- 26805595 TI - Generation of virus-like particles for emerging epizootic haemorrhagic disease virus: Towards the development of safe vaccine candidates. AB - Epizootic haemorrhagic disease virus (EHDV) is an insect-transmitted pathogen which causes high mortality in deer populations and may also cause high morbidity in cattle. EHDV belongs to the Orbivirus genus and is closely related to the prototype Bluetongue virus (BTV). To date seven distinct serotypes have been recognized. However, a live-attenuated vaccine is commercially available against only one serotype namely EHDV-2, which has been responsible for multiple outbreaks in North America, Canada, Asia and Australia. Here we expressed four major capsid proteins (VP2, VP3, VP5 and VP7) of EHDV-1 using baculovirus multiple gene expression systems and demonstrated that three-layered VLPs were assembled mimicking the authentic EHDV particles but lacking the viral genomic RNA segments and the transcriptase complex (TC). Antibodies generated with VLPs not only neutralized EHDV-1 infection in cell culture but also showed cross neutralizing reactivity against two other serotypes, EHDV-2 and EHDV-6. For proof of concept, we demonstrated that EHDV-2 VLPs could be generated rapidly by expressing the EHDV-2 variable outer capsid proteins (VP2, VP5) together with EHDV-1 VP3 and VP7, the two inner capsid proteins, which are highly conserved among the 7 serotypes. Data presented in this study validate the VLPs as a potential vaccine and demonstrate that a vaccine could be developed rapidly in the event of an outbreak of a new serotype. PMID- 26805594 TI - Use of 4beta-hydroxycholesterol in animal and human plasma samples as a biomarker for CYP3A induction. AB - BACKGROUND: 4beta-hydroxycholesterol (4betaHC) has recently been proposed as a potential endogenous biomarker for CYP3A activity. Developing bioanalytical assays for 4betaHC is challenging for several reasons, including endogenous background levels in plasma; the presence of free and ester forms; the inherent lack of MS sensitivity; and the presence of multiple positional isomers. RESULTS: Bioanalytical assays in mouse, rat, dog and human plasma were adapted and modified from a previous published human plasma assay for 4betaHC by using alkaline de-esterification, picolinic derivatization, a surrogate analyte (d7 4betaHC) in authentic matrices and chromatographic conditions that showed good separation from isobaric, positional isomers. CONCLUSION: These assays were applied to multiple studies and demonstrated potential applications of 4betaHC as a CYP3A biomarker across preclinical and clinical settings. PMID- 26805596 TI - Report on: "The 1st Workshop on National Immunization Programs and Vaccine Coverage in ASEAN Countries, April 30, 2015, Pattaya, Thailand". AB - The 1st Workshop on National Immunization Programs and Vaccine Coverage in Association of Southeast Asian Nations (ASEAN) Countries Group (WNIPVC-ASEAN) held a meeting on April 30, 2015, Pattaya, Thailand under the auspices of the Pediatric Infectious Diseases Society and the World Health Organization (WHO). Reports on the current status and initiatives of the national immunization program (NIP) in each ASEAN countries that attended were presented. These reports along with survey data collected from ministries of health in ASEAN countries NIPs demonstrate that good progress has been made toward the goal of the Global Vaccine Action Plan (GVAP). However, some ASEAN countries have fragile health care systems that still have insufficient vaccine coverage of some basic EPI antigens. Most ASEAN countries still do not have national coverage of some new and underused vaccines, and raising funds for the expansion of NIPs is challenging. Also, there is insufficient research into disease burden of vaccine preventable diseases and surveillance. Health care workers must advocate NIPs to government policy makers and other stakeholders as well as improve research and surveillance to achieve the goals of the GVAP. PMID- 26805597 TI - Diclofenac in municipal wastewater treatment plant: quantification using laser diode thermal desorption--atmospheric pressure chemical ionization--tandem mass spectrometry approach in comparison with an established liquid chromatography electrospray ionization-tandem mass spectrometry method. AB - Diclofenac (DCF), a prevalent non-steroidal anti-inflammatory drug (NSAID) is often detected in wastewater and surface water. Analysis of the pharmaceuticals in complex matrices is often laden with challenges. In this study a reliable, rapid and sensitive method based on laser diode thermal desorption/atmospheric pressure chemical ionization (LDTD/APCI) coupled with tandem mass spectrometry (MS/MS) has been developed for the quantification of DCF in wastewater and wastewater sludge. An established conventional LC-ESI-MS/MS (liquid chromatography-electrospray ionization-tandem mass spectrometry) method was compared with LDTD-APCI-MS/MS approach. The newly developed LDTD-APCI-MS/MS method reduced the analysis time to 12s in lieu of 12 min for LC-ESI-MS/MS method. The method detection limits for LDTD-APCI-MS/MS method were found to be 270 ng L(-1) (LOD) and 1000 ng L(-1) (LOQ). Furthermore, two extraction procedures, ultrasonic assisted extraction (USE) and accelerated solvent extraction (ASE) for the extraction of DCF from wastewater sludge were compared and ASE with 95.6 +/- 7% recovery was effective over USE with 86 +/- 4% recovery. The fate and partitioning of DCF in wastewater (WW) and wastewater sludge (WWS) in wastewater treatment plant was also monitored at various stages of treatment in Quebec Urban community wastewater treatment plant. DCF exhibited affinity towards WW than WWS with a presence about 60% of DCF in WW in contrary with theoretical prediction (LogKow=4.51). PMID- 26805598 TI - A flow injection MU-solid phase extraction system based on electrospun polyaniline nanocomposite. AB - In this study, a fast and sensitive flow injection MU-solid phase extraction (FI MU-SPE) technique based on an electrospun polyaniline (PANI) nanocomposite in conjunction with gas chromatography-mass spectrometry (GC-MS) was developed. The PANI-based nanocomposite was synthesized by electrospinning of a solution containing polyvinyl alcohol (PVA)/PANI. The majority of PVA template was subsequently removed from the whole PVA/PANI nanofibers blend by exposing the electrospun nanocomposite to hot water. The homogeneity, porosity and characterization of the electrospun nanofibers were investigated by the scanning electron microscopy (SEM) and Fourier transform infrared (FT-IR) spectroscopy. Due to the polar-oriented nature of the prepared nanofibrous nitrogen-containing sorbent, its capability was examined by FI-MU-SPE of some selected triazines, as model compounds, from aquatic media. After optimizing the extraction conditions, the intraday relative standard deviation values for a double distilled water spiked with the selected triazines were in range of 8.9-9.5% (n=3) while the limits of detection were between 0.03-0.09 ng mL(-1). The linearity of the method was in the concentration range of 0.1-500 ng mL(-1). The proficiency of the developed method was validated by analyzing paddy, well and tap water samples and the relative recovery values were found to be in the range of 83-95% under the optimized conditions. PMID- 26805599 TI - General theory of peak compression in liquid chromatography. AB - A new and general expression of the peak compression factor in liquid chromatography is derived. It applies to any type of gradients induced by non uniform columns (stationary) or by temporal variations (dynamic) of the elution strength related to changes in solvent composition, temperature, or in any external field. The new equation is validated in two ideal cases for which the exact solutions are already known. From a practical viewpoint, it is used to predict the achievable degree of peak compression for curved retention models, retained solvent gradients, and for temperature-programmed liquid chromatography. The results reveal that: (1) curved retention models affect little the compression factor with respect to the best linear strength retention models, (2) gradient peaks can be indefinitely compressed with respect to isocratic peaks if the propagation speed of the gradient (solvent or temperature) becomes smaller than the chromatographic velocity, (3) limitations are inherent to the maximum intensity of the experimental intrinsic gradient steepness, and (4) dynamic temperature gradients can be advantageously combined to solvent gradients in order to improve peak capacities of microfluidic separation devices. PMID- 26805600 TI - Analytical methods for the endocrine disruptor compounds determination in environmental water samples. AB - The potential risk of exposure to different xenobiotics, which can modulate the endocrine system and represent a treat for the wellness of an increasing number of people, has recently drawn the attention of international environmental and health agencies. Several agents, characterized by structural diversity, may interfer with the normal endocrine functions that regulate cell growth, homeostasis and development. Substances such as pesticides, herbicides, plasticizers, metals, etc. having endocrine activity (EDCs) are used in agriculture and industry and are also used as drugs for humans and animals. A difficulty in the analytical determination of these substances is the complexity of the matrix in which they are present. In fact, the samples most frequently analyzed consist of groundwater and surface water, including influent and effluent of wastewater treatment plants and drinking water. In this review, several sample pretreatment protocols, assays and different instrumental techniques recently used in the EDCs determination have been considered. This review concludes with a paragraph in which the most recent hyphenated-instrument techniques are treated, highlighting their sensitivity and selectivity for the analyses of environmental water samples. PMID- 26805601 TI - Conformational plasticity of IgG during protein A affinity chromatography. AB - Single step elution of a protein A column with 100mM acetate pH 3.5 produced a curvilinear gradient with pH dropping steeply at first then more gradually as it approached endpoint. IgG with a native hydrodynamic diameter of 11.5 nm began to elute at pH 6.0 with a size of 9.4 nm. IgG size continued to decrease across the peak, reaching a minimum of 2.2 nm at pH 3.9. Secondary structure of early eluting IgG was only mildly affected but later eluting fractions became increasingly non-native with the 2.2 nm population exhibiting the highest proportion of beta-sheet and lowest random coil of all conformations. Size reduction and structural change of IgG through this portion of the elution peak were attributed dominantly to a pre-existing tendency of highly concentrated IgG to adopt reduced size conformations at low pH and conductivity, facilitated by the known conformational relaxation of IgG by its interaction with protein A. IgG size increased to 10.4 nm as elution pH approached 3.5 across the tailing fractions. Major loss of beta-sheet and increase of alpha-helix and random coil were observed in parallel. Late elution of this population was attributed to it being eluted from interactions with 2 distinct protein A domains, one bound to each side of the Fc region, creating a higher dissociation constant than single site Fc-protein A interactions, and requiring more severely disruptive conditions for elution. The high degree of conformational disruption was attributed to simultaneous interaction of both heavy chains with protein A. PMID- 26805602 TI - Understanding of multimetallic cluster growth. AB - The elucidation of formation mechanisms is mandatory for understanding and planning of synthetic routes. For (bio-)organic and organometallic compounds, this has long been realized even for very complicated molecules, whereas the formation of ligand-free inorganic molecules has widely remained a black box to date. This is due to poor structural relationships between reactants and products and the lack of structurally related intermediates--due to the comparably high coordination flexibility of involved atoms. Here we report on investigations of the stepwise formation of multimetallic clusters, based on a series of crystal structures and complementary quantum-chemical studies of (Ge2As2)(2-), (Ge7As2)(2 ), [Ta@Ge6As4](3-), [Ta@Ge8As4](3-) and [Ta@Ge8As6](3-). The study makes use of efficient quantum-chemical tools, enabling the first detailed screening of the energy hypersurface along the formation of ligand-free inorganic species for a semi-quantitative picture. The results can be generalized for an entire family of multimetallic clusters. PMID- 26805603 TI - Expression of estrus before fixed-time AI affects conception rates and factors that impact expression of estrus and the repeatability of expression of estrus in sequential breeding seasons. AB - Expression of estrus after PG and before fixed-time AI has been reported to change the uterine environment, increase accessory sperm numbers, fertilization rates, and overall embryo survival. Thus, expression of estrus can strongly impact overall pregnancy success. Because of variation in percentage of beef females detected in estrus and number of animals per study, it can be difficult to detect a significant effect of estrus on pregnancy success. Thus, a meta analysis was conducted using data from 10,116 beef females in 22 studies that utilized variations of the 5 most common fixed-time AI protocols (CO-Synch, 7-day CO-Synch+CIDR, 5-day CIDR, PG 6-day CIDR, and the 14-day CIDR protocols) to examine the effect of detection in standing estrus on subsequent fixed-time AI pregnancy success. A random-effects model was used to combine the studies/herds. The overall model indicated a positive effect of estrus on conception rates with cows detected in estrus before fixed-time AI having a 27% greater (P<0.05; 95% CI=22-32%) conception rate compared with those not detected in estrus. Next we determined factors that influenced expression of estrus. Data were available on 547 cows synchronized with a CIDR based fixed-time AI protocols and observed for estrus before AI during 2-4 breeding seasons. Analysis of these cows indicated that days postpartum (P=0.22) did not impact estrous expression. In contrast, BCS influenced estrous expression (P=0.04) with cows in a BCS of <=4 (51+/-5%) having decreased expression of estrus compared to cows with a BCS>4 (>=70+/-4%). Initiation of estrous cycles before the breeding season also influenced estrous expression (P=0.03), with anestrous cows having greater expression of estrus compared with estrus-cycling cows (78+/-5% vs. 70+/-5%, respectively). In conclusion, among all currently recommended fixed-time AI protocols, cows detected in estrus before fixed-time AI had improved conception rates, with BCS and estrus-cycling status having the greatest influence on expression of estrus. PMID- 26805604 TI - Is first trimester vitamin D status in nulliparous women associated with pregnancy related hypertensive disorders? AB - OBJECTIVES: this study aimed to explore if maternal vitamin D status in early pregnancy was associated with pre-eclampsia and pregnancy-induced hypertension. Relationships between vitamin D status and blood pressure at the start of pregnancy as well as the occurrence of a mid-pregnancy drop in blood pressure were also explored. This secondary analysis was completed to investigate a possible mechanism for the association between vitamin D status and pregnancy related hypertensive disorders. DESIGN AND SETTING: data were obtained from the Amsterdam Born Children and their Development study, a prospective community based cohort study based in Amsterdam, The Netherlands. PARTICIPANTS: a total of 2074 nulliparous women without pre-existing hypertension and with a known vitamin D status before 17 weeks gestation were included in the study. Vitamin D status was categorized into four groups: "normal" (>=50nmol/L), "insufficient" (30 49.9nmol/L) "deficient" (20-29.9nmol/L) or "severely deficient" (<20nmol/L). MEASUREMENTS: logistic regression analysis was used to investigate if vitamin D status was related to the odds of experiencing pre-eclampsia or pregnancy-induced hypertension. Models were corrected for maternal age, ethnicity, pre-pregnancy BMI, smoking and socioeconomic status. chi(2) and ANOVA tests were used to investigate relationships between vitamin D status and the blood pressure parameters. FINDINGS: when compared to women with a normal vitamin D status, women who were severely deficient had an increased risk for pre-eclampsia (OR 2.08; 95% CI, 1.05-4.13), but the association was rendered non-significant after correction (OR 1.88; 95% CI 0.79-4.48). There were no associations between vitamin D status and pregnancy-induced hypertension, starting blood pressure or the occurrence of a mid-pregnancy drop in blood pressure. KEY CONCLUSIONS: no strong evidence was found for an association between first trimester vitamin D status and pregnancy related hypertensive disorders in nulliparous women. IMPLICATIONS FOR PRACTICE: at this time, vitamin D supplementation is not warranted for the specific purpose of preventing pregnancy related hypertensive disorders. PMID- 26805605 TI - Intimate partner violence and the experience of early motherhood: A cross sectional analysis of factors associated with a poor experience of motherhood. AB - OBJECTIVE: to examine the relationship between intimate partner violence and other factors associated with the experience of early motherhood. DESIGN: cross sectional secondary data analysis (n=1534) from MOVE: a cluster randomised controlled trial that evaluated a model of enhanced nurse screening and supportive care for abused women. SETTING: Victoria, Australia. PARTICIPANTS: postpartum women attending community based maternal and child health clinics. MEASUREMENTS: survey included the Experience of Motherhood Questionnaire; measures of partner abuse, depression, anxiety, stress and social support. Multivariable robust regression analysis used. FINDINGS: independent of other factors, abused women were more likely to have a poorer mothering experience (Adj b=2.01, 95% CI=0.78, 3.25). Poor mental health, abuse as a child and being born overseas were also associated with a poor experience. Busy mothers who had a multiple birth and those balancing work and study simultaneously had higher experience of motherhood scores, indicating a poorer experience. Social support was protective. KEY CONCLUSIONS AND IMPLICATIONS: exposure to partner violence is adversely associated with early motherhood, independent of other correlates of poor motherhood experience. Greater awareness of factors associated with intimate partner violence and mothering would enable health care professionals and policy makers to improve support for women and children experiencing violence. PMID- 26805607 TI - A longitudinal analysis of the effects of age on the blood plasma metabolome in the common marmoset, Callithrix jacchus. AB - Primates tend to be long-lived for their size with humans being the longest lived of all primates. There are compelling reasons to understand the underlying age related processes that shape human lifespan. But the very fact of our long lifespan that makes it so compelling, also makes it especially difficult to study. Thus, in studies of aging, researchers have turned to non-human primate models, including chimpanzees, baboons, and rhesus macaques. More recently, the common marmoset, Callithrix jacchus, has been recognized as a particularly valuable model in studies of aging, given its small size, ease of housing in captivity, and relatively short lifespan. However, little is known about the physiological changes that occur as marmosets age. To begin to fill in this gap, we utilized high sensitivity metabolomics to define the longitudinal biochemical changes associated with age in the common marmoset. We measured 2104 metabolites from blood plasma at three separate time points over a 17-month period, and we completed both a cross-sectional and longitudinal analysis of the metabolome. We discovered hundreds of metabolites associated with age and body weight in both male and female animals. Our longitudinal analysis identified age-associated metabolic pathways that were not found in our cross-sectional analysis. Pathways enriched for age-associated metabolites included tryptophan, nucleotide, and xenobiotic metabolism, suggesting these biochemical pathways might play an important role in the basic mechanisms of aging in primates. Moreover, we found that many metabolic pathways associated with age were sex specific. Our work illustrates the power of longitudinal approaches, even in a short time frame, to discover novel biochemical changes that occur with age. PMID- 26805608 TI - The joint association of depression and cognitive function with severe disability among community-dwelling older adults in Finland, Poland and Spain. AB - OBJECTIVES: To explore the joint association of depression and cognitive function with severe disability in nationally-representative samples of community-dwelling adults aged 50 years and older from Finland, Poland and Spain. DESIGN: Cross sectional. SETTING: Community-based. PARTICIPANTS: Population-based sample of 7987 non-institutionalized adults aged 50 and older. MEASUREMENTS: The outcome was severe disability, defined as >= 90th percentile of the 12-item version of the World Health Organization Disability Assessment Schedule (WHODAS 2.0). Past 12-month DSM-IV major depressive disorder was assessed with the depression module of the WHO Composite International Diagnostic Interview (CIDI). A global cognitive function score was obtained through neuropsychological tests. Product terms between depression and cognition were introduced in multivariable logistic regression models to test for interaction. RESULTS: Lower cognitive function and depression were both significantly associated with severe disability in all countries. A significant interaction was only found in Finland where the ORs (95% CIs) of depression for severe disability at the 25th (worse), 50th, and 75th (better) percentiles of cognitive function were 7.26 (4.28-12.32), 11.1 (6.7 18.38), and 17.56 (9.29-33.2), respectively. CONCLUSION: People with depression and cognitive decline are likely to benefit from the usual evidence-based treatments to reduce the burden of disability. However, in Finland, those with better cognitive function may benefit from more aggressive depression treatment. Future research is warranted to assess whether our results may be replicated. PMID- 26805609 TI - Towards parsimonious ecophysiological models that bridge ecology and agronomy. PMID- 26805610 TI - Risk of unintended pregnancy based on intended compared to actual contraceptive use. AB - BACKGROUND: After initiating a new contraceptive method, the provider has little control of how or whether that method is used. OBJECTIVE: We sought to compare unintended pregnancy rates by the initial chosen contraceptive method after counseling to traditional contraceptive effectiveness in the same study population. STUDY DESIGN: The Contraceptive CHOICE Project provided reversible contraception to 9252 women at no cost during 2-3 years of follow-up. We performed 2 analyses of contraceptive efficacy in this prospective cohort: (1) intent-to-use (ITU), grouping participants based on their chosen method at enrollment; and (2) as-used, categorizing participant time according to the method used. In ITU analysis, switching of methods and method continuation were not considered, as we wanted to assess outcomes based on the method chosen at baseline. We used Cox proportional hazards models to compare rates of unintended pregnancy. RESULTS: During 20,017 person-years, we identified 615 unintended pregnancies. In ITU analysis, pregnancy rates were 5.3, 5.5, 2.0, 1.7, and 1.9 per 100 person-years for women initiating oral, injectable, implantable, copper, and hormonal intrauterine contraception (IUC) at baseline, respectively. The adjusted hazard ratio for injectable contraception compared to hormonal IUC was 2.4 (95% confidence interval, 1.8-3.3). Delaying initiation of IUC or implantable contraception increased unintended pregnancies by 60% (adjusted hazard ratio, 1.6; 95% confidence interval, 1.2-2.0). In as-used analysis, pregnancy rates were 6.7, 1.6, 0.2, 0.6, and 0.2 per 100 person-years for women using oral, injectable, implantable, copper, and hormonal IUC, respectively. CONCLUSION: Although highly effective in the as-used analysis, women initially choosing injectable contraception had pregnancy rates similar to oral contraception and significantly worse than IUC or implantable contraception. Despite switching and discontinuation, women choosing an IUC or implantable contraception at baseline were much less likely to have an unintended pregnancy compared to those selecting other methods. PMID- 26805611 TI - European operative registry to avoid complications in operative gynecology. AB - The aim of this study is to determine how complications can be avoided in gynecological minimally invasive surgery in Europe. The Norwegian Gynecological Endoscopic Registry (NGER) facilitates medical research over a long duration. Can experiences from the Norwegian registry be used to develop a European registry to avoid complications? To answer this question, we used the NGER data from February 2013 until March 2015 to analyze the complications of gynecological endoscopy. The registry includes sociodemographic factors, related comorbidity, previous surgery, present procedure, and intraoperative complications. Postoperative complications were identified with a questionnaire administered 4 weeks after surgery. The risk factors leading to complications in gynecological endoscopy were found to be obesity, diabetes mellitus, heart disease, hypertension, previous surgery due to cervical carcinoma in situ, and low educational level. Regional differences in the complication rate were noted. National web-based operation registries such as the NGER can identify the risk factors for complications of gynecological endoscopic surgery and can help improve the outcome after surgery. The experience from NGER can be used to establish a European register. PMID- 26805612 TI - Induction of Calcium Influx in Cortical Neural Networks by Nanomagnetic Forces. AB - Nanomagnetic force stimulation with ferromagnetic nanoparticles was found to trigger calcium influx in cortical neural networks without observable cytotoxicity. Stimulated neural networks showed an average of 20% increment in calcium fluorescence signals and a heightened frequency in calcium spiking. These effects were also confined spatially to areas with engineered high magnetic field gradients. Furthermore, blockage of N-type calcium channels inhibited the stimulatory effects of the nanomagnetic forces, suggesting the role of mechano sensitive ion channels in mediating calcium influx. PMID- 26805613 TI - Proteomic response of the phytopathogen Phyllosticta citricarpa to antimicrobial volatile organic compounds from Saccharomyces cerevisiae. AB - Volatile organic compounds (VOCs) released by Saccharomyces cerevisiae inhibit plant pathogens, including the filamentous fungus Phyllosticta citricarpa, causal agent of citrus black spot. VOCs mediate relevant interactions between organisms in nature, and antimicrobial VOCs are promising, environmentally safer fumigants to control phytopathogens. As the mechanisms by which VOCs inhibit microorganisms are not well characterized, we evaluated the proteomic response in P. citricarpa after exposure for 12h to a reconstituted mixture of VOCs (alcohols and esters) originally identified in S. cerevisiae. Total protein was extracted and separated by 2D-PAGE, and differentially expressed proteins were identified by LC-MS/MS. About 600 proteins were detected, of which 29 were downregulated and 11 were upregulated. These proteins are involved in metabolism, genetic information processing, cellular processes, and transport. Enzymes related to energy generating pathways, particularly glycolysis and the tricarboxylic acid cycle, were the most strongly affected. Thus, the data indicate that antimicrobial VOCs interfere with essential metabolic pathways in P. citricarpa to prevent fungal growth. PMID- 26805614 TI - Gibberellins in Penicillium strains: Challenges for endophyte-plant host interactions under salinity stress. AB - The genus Penicillium is one of the most versatile "mycofactories", comprising some species able to produce gibberellins, bioactive compounds that can modulate plant growth and development. Although plants have the ability to synthesize gibberellins, their levels are lower when plants are under salinity stress. It has been recognized that detrimental abiotic conditions, such as saline stress, have negative effects on plants, being the availability of bioactive gibberellins a critical factor for their growth under this conditions. This review summarizes the interplay existing between endophytic Penicillium strains and plant host interactions, with focus on bioactive gibberellins production as a fungal response that allows plants to overcome salinity stress. PMID- 26805615 TI - Localization and characterization of two putative TMH family proteins in Chlamydia psittaci. AB - Chlamydia psittaci (C. psittaci), an obligate intracellular agent of psittacosis, causes an atypical pneumonia in humans. The transmembrane head proteins (TMH) of C. psittaci, putatively belong to the Inc family and presumably play similar roles. CPSIT_0844 and CPSIT_0846 were the putative TMH proteins of C. psittaci. To identify these two proteins, antisera were raised with fusion proteins which were prokaryotic expressed in Escherichia coli and purified. By immunofluorescence assay, CPSIT_0844 and CPSIT_0846 were localized in the inclusion membrane of C. psittaci-infected cells. By RT-PCR and western blot analysis to detect the temporal expression, CPSIT_0844 and CPSIT_0846 were detected as early as 12h post-infection (p.i.) and 6h p.i., separately; meanwhile, in secretions monitored with immunofluorescence assay, these proteins were observed in the inclusion membrane at 18h p.i. and remained in the inclusion membrane throughout the growth cycle. CPSIT_0844 and CPSIT_0846 could specifically be recognized by the antiserum of C. psittaci but failed to react with the antiserums of Chlamydia trachomatis and Chlamydia pneumoniae, which is consistent with the fact that they had no significant orthologs in C. trachomatis and C. pneumoniae. These results revealed that CPSIT_0844 and CPSIT_0846, the putative TMH family proteins, might be unique to C. psittaci and could be used to diagnose the infection caused by C. psittaci. Moreover, CPSIT_0844 and CPSIT_0846 could induce the expression of the inflammatory cytokines IL-1beta, IL-6 and TNF alpha in THP-1 cells, which might contribute to chlamydia-induced inflammatory pathologies. PMID- 26805616 TI - Bacteria and fungi can contribute to nutrients bioavailability and aggregate formation in degraded soils. AB - Intensive agricultural practices and cultivation of exhaustive crops has deteriorated soil fertility and its quality in agroecosystems. According to an estimate, such practices will convert 30% of the total world cultivated soil into degraded land by 2020. Soil structure and fertility loss are one of the main causes of soil degradation. They are also considered as a major threat to crop production and food security for future generations. Implementing safe and environmental friendly technology would be viable solution for achieving sustainable restoration of degraded soils. Bacterial and fungal inocula have a potential to reinstate the fertility of degraded land through various processes. These microorganisms increase the nutrient bioavailability through nitrogen fixation and mobilization of key nutrients (phosphorus, potassium and iron) to the crop plants while remediate soil structure by improving its aggregation and stability. Success rate of such inocula under field conditions depends on their antagonistic or synergistic interaction with indigenous microbes or their inoculation with organic fertilizers. Co-inoculation of bacteria and fungi with or without organic fertilizer are more beneficial for reinstating the soil fertility and organic matter content than single inoculum. Such factors are of great importance when considering bacteria and fungi inocula for restoration of degraded soils. The overview of presented mechanisms and interactions will help agriculturists in planning sustainable management strategy for reinstating the fertility of degraded soil and assist them in reducing the negative impact of artificial fertilizers on our environment. PMID- 26805617 TI - Diversity of bacterial endophytes in 3 and 15 year-old grapevines of Vitis vinifera cv. Corvina and their potential for plant growth promotion and phytopathogen control. AB - This study represents the first investigation on ecology of endophytic bacteria isolated from 3 and 15 year-old vine stems of Vitis vinifera cv. Corvina. The analysis was performed by means of culture-dependent techniques. The obtained results showed that new grapevine endophytic genera are being discovered. Moreover, Bacilli and Actinobacteria are frequently isolated from 3 year-old plants, whereas Alpha- and Gamma- Proteobacteria classes are more prevalent in the 15 year-old plants. Shannon-Wiener (H) index and analysis of rarefaction curves revealed greater genus richness in young grapevine plants. Furthermore, results evidenced an increase of genotypic group number within specific genera (e.g., Rhizobium and Pantoea). Among isolated strains from 3 and 15 year-old stems, respectively, 34 and 39% produce siderophores; 22 and 15% secrete ammonia; 22 and 21% produce indole-3-acetic acid; 8.7 and 41% solubilize phosphate. Besides, two strains isolated from 15 year-old grapevines showed 1 aminocyclopropane-1-carboxylate deaminase activity. Antifungal activity analysis evidenced that two Bacillus strains possess growth antagonistic effect toward all the tested fungal strains. Therefore, the present study extends our knowledge of the diversity of the endophytic bacteria by providing new insights into the complexity of the grapevine microbiome. PMID- 26805618 TI - Immunodiagnosis and molecular validation of Toxoplasma gondii-recombinant dense granular (GRA) 7 protein for the detection of toxoplasmosis in patients with cancer. AB - Serological assays for the diagnosis of toxoplasmosis mostly rely on the tachyzoite specific antigens of Toxoplasma gondii, which are difficult to produce by conventional methods. The aim of this study was to clone and express of GRA7 protein of T. gondii and evaluate its potential for immunodiagnosis of toxoplasmosis in cancer patients. As well as validate the results using a new molecular assay, LAMP technique. The GRA7 gene was successfully cloned, expressed and purified by affinity chromatography and the production was evaluated by SDS PAGE, dot blot and western blot analyses. The rGRA7 was used for developing an ELISA based on the rGRA7 using sera from patients with toxoplasmosis and healthy controls. Furthermore, 50 serum samples from leukemic children infected with toxoplasmosis and 50 seronegative controls were included to evaluate the sensitivity and specificity of rGRA7 based ELISA. Finally, the LAMP technique was used to assess the accuracy and validity of the results obtained by rGRA7 based ELISA. The consistency of the results of two tests was determined by using the Kappa coefficient of agreement. The rGRA7 showed higher and optimum immunoreactivity with 1:100 dilution of serum from Toxoplasma infected patients. The sensitivity and specificity of test were calculated as 92 and 94%, respectively. According to the Kappa coefficient of agreement, there was a significant conformance between the results obtained by ELISA based on the rGRA7 and the results of LAMP technique (~96%, P<0.001). Findings of the present study showed that rGRA7 can be used as a potential immunogenic antigen for developing immunodiagnostic tools for immunodiagnosis of toxoplasmosis in patients including patients with cancer. PMID- 26805619 TI - AdeR protein regulates adeABC expression by binding to a direct-repeat motif in the intercistronic spacer. AB - Overexpression of the efflux pump AdeABC is associated with tigecycline resistance of multi-drug resistant Acinetobacter baumannii (MDRAB). A two component regulatory system, sensor AdeS and regulator AdeR proteins regulate the pump. However, the detailed mechanism of the AdeR protein to enhance the expression of adeABC operon is not well defined. We illustrated the biological characteristics of AdeR proteins by comparing a mutant AdeR protein of a tigecycline resistant MDRAB to the wild AdeR protein. By analyzing a series of deletion constructs, a minimal gene cassette of the intercistronic spacer DNA fragment specifically bound with the adeR protein and resulted in band shifting in electrophoresis mobility shifting assays (EMSA). A conserve direct repeat motif was observed in the intercistronic spacer DNA. We demonstrated the AdeR protein was a direct-repeat-binding protein. Two common residue mutations on the AdeR proteins of tigecycline resistant MDRAB isolates could reduce their binding affinity with the intercistronic spacer. The free intercistronic spacer may then more efficiently support the read-through of the adeABC operon during the co transcriptional translation in tigecycline resistant MDRAB isolates. PMID- 26805620 TI - Multifunctionality and diversity of culturable bacterial communities strictly associated with spores of the plant beneficial symbiont Rhizophagus intraradices. AB - Arbuscular Mycorrhizal Fungi (AMF) live in symbiosis with most crop plants and represent essential elements of soil fertility and plant nutrition and productivity, facilitating soil mineral nutrient uptake and protecting plants from biotic and abiotic stresses. These beneficial services may be mediated by the dense and active spore-associated bacterial communities, which sustain diverse functions, such as the promotion of mycorrhizal activity, biological control of soilborne diseases, nitrogen fixation, and the supply of nutrients and growth factors. In this work, we utilised culture-dependent methods to isolate and functionally characterize the microbiota strictly associated to Rhizophagus intraradices spores, and molecularly identified the strains with best potential plant growth promoting (PGP) activities by 16S rDNA sequence analysis. We isolated in pure culture 374 bacterial strains belonging to different functional groups-actinobacteria, spore-forming, chitinolytic and N2-fixing bacteria-and screened 122 strains for their potential PGP activities. The most common PGP trait was represented by P solubilization from phytate (69.7%), followed by siderophore production (65.6%), mineral P solubilization (49.2%) and IAA production (42.6%). About 76% of actinobacteria and 65% of chitinolytic bacteria displayed multiple PGP activities. Nineteen strains with best potential PGP activities, assigned to Sinorhizobium meliloti, Streptomyces spp., Arthrobacter phenanthrenivorans, Nocardiodes albus, Bacillus sp. pumilus group, Fictibacillus barbaricus and Lysinibacillus fusiformis, showed the ability to produce IAA and siderophores and to solubilize P from mineral phosphate and phytate, representing suitable candidates as biocontrol agents, biofertilisers and bioenhancers, in the perspective of targeted management of beneficial symbionts and their associated bacteria in sustainable food production systems. PMID- 26805621 TI - Role of phosphate solubilizing Burkholderia spp. for successful colonization and growth promotion of Lycopodium cernuum L. (Lycopodiaceae) in lateritic belt of Birbhum district of West Bengal, India. AB - Profuse growth of Lycpodium cernuum L. was found in phosphate deficient red lateritic soil of West Bengal, India. Interaction of vesicular-arbuscular mycorrhiza (VAM) with Lycopodium rhizoids were described earlier but association of PGPR with their rhizoids were not studied. Three potent phosphate solubilizing bacterial strains (P4, P9 and P10) associated with L. cernuum rhizoids were isolated and identified by 16S rDNA homologies on Ez-Taxon database as Burkholderia tropica, Burkholderia unamae and Burkholderia cepacia respectively. Day wise kinetics of phosphate solubilization against Ca3(PO4)2 suggested P4 (580.56+/-13.38 MUg ml(-1)) as maximum mineral phosphate solubilizer followed by P9 (517.12+/-17.15 MUg ml(-1)) and P10 (485.18+/-14.23 MUg ml(-1)) at 28 degrees C. Release of bound phosphates by isolated strains from ferric phosphate (FePO4), aluminum phosphate (AlPO4) and four different complex rock phosphates indicated their very good phosphate solubilizng efficacy. Nitrogen independent solubilizition also supports their nitrogen fixing capabilities. Inhibition of P solubilization by calcium salts and induction by EDTA suggested pH dependent chelation of metal cations by all of the isolates. Rhizoidal colonization potentials of Burkholderia spp. were confirmed by in planta experiment and also using scanning electron microscope (SEM). Increases of total phosphate content in Lycopodium plants upon soil treatment with these isolates were also recorded. In addition siderophore production on CAS agar medium, tryptophan dependent IAA production and antifungal activities against pathogenic fungi by rhizospheric isolates deep-rooted that they have definite role in nutrient mobilization for successful colonization of L. cernuum in nutrient deficient lateritic soil. PMID- 26805622 TI - Plant growth-promoting bacterial endophytes. AB - Bacterial endophytes ubiquitously colonize the internal tissues of plants, being found in nearly every plant worldwide. Some endophytes are able to promote the growth of plants. For those strains the mechanisms of plant growth-promotion known to be employed by bacterial endophytes are similar to the mechanisms used by rhizospheric bacteria, e.g., the acquisition of resources needed for plant growth and modulation of plant growth and development. Similar to rhizospheric plant growth-promoting bacteria, endophytic plant growth-promoting bacteria can act to facilitate plant growth in agriculture, horticulture and silviculture as well as in strategies for environmental cleanup (i.e., phytoremediation). Genome comparisons between bacterial endophytes and the genomes of rhizospheric plant growth-promoting bacteria are starting to unveil potential genetic factors involved in an endophytic lifestyle, which should facilitate a better understanding of the functioning of bacterial endophytes. PMID- 26805623 TI - Antagonistic activity of fungi of Olea europaea L. against Colletotrichum acutatum. AB - Fungi naturally present in olive trees were identified and tested for their antagonistic potential against Colletotrichum acutatum. A total of 14 isolates were identified, 12 belonged to genera Alternaria, Epicoccum, Fusarium, Aspergillus, Anthrinium, Chaetomium, Diaporthe, Nigrospora, one to family Xylariaceae and one was unclassified. All fungal isolates showed some inhibitory action over the growth of C. acutatum during dual culture growth, however, when agar-diffusible tests were performed only five fungal isolates caused C. acutatum growth inhibition: Alternaria sp. isolate 2 (26.8%), the fungus from Xylariaceae family (14.3%), Alternaria sp. isolate 1 (10.7%); Diaporthe sp. (10.7%), Nigrospora oryzae (3.5%). Volatile substances produced by these isolates were identified through gas-chromatography techniques, as phenylethyl alcohol, 4 methylquinazoline, benzothiazole, benzyl alcohol, lilial, galaxolide, among others. These inhibitory volatiles could play a significant role in reduction of C. acutatum expansion in olive and their study as potential biocontrol agents should be further explored. PMID- 26805624 TI - Biochemical and molecular tools reveal two diverse Xanthomonas groups in bananas. AB - Xanthomonas campestris pv. musacearum (Xcm) causing the banana Xanthomonas wilt (BXW) disease has been the main xanthomonad associated with bananas in East and Central Africa based on phenotypic and biochemical characteristics. However, biochemical methods cannot effectively distinguish between pathogenic and non pathogenic xanthomonads. In this study, gram-negative and yellow-pigmented mucoid bacteria were isolated from BXW symptomatic and symptomless bananas collected from different parts of Uganda. Biolog, Xcm-specific (GspDm), Xanthomonas vasicola species-specific (NZ085) and Xanthomonas genus-specific (X1623) primers in PCR, and sequencing of ITS region were used to identify and characterize the isolates. Biolog tests revealed several isolates as xanthomonads. The GspDm and NZ085 primers accurately identified three isolates from diseased bananas as Xcm and these were pathogenic when re-inoculated into bananas. DNA from more isolates than those amplified by GspDm and NZ085 primers were amplified by the X1623 primers implying they are xanthomonads, these were however non-pathogenic on bananas. In the 16-23 ITS sequence based phylogeny, the pathogenic bacteria clustered together with the Xcm reference strain, while the non-pathogenic xanthomonads isolated from both BXW symptomatic and symptomless bananas clustered with group I xanthomonads. The findings reveal dynamic Xanthomonas populations in bananas, which can easily be misrepresented by only using phenotyping and biochemical tests. A combination of tools provides the most accurate identity and characterization of these plant associated bacteria. The interactions between the pathogenic and non-pathogenic xanthomonads in bananas may pave way to understanding effect of microbial interactions on BXW disease development and offer clues to biocontrol of Xcm. PMID- 26805625 TI - Synthesis of vinylphosphines and unsymmetric diphosphines: iron-catalyzed selective hydrophosphination reaction of alkynes and vinylphosphines with secondary phosphines. AB - Iron complex-catalyzed regioselective single hydrophosphination of terminal arylalkynes with secondary phosphines was achieved. Unsymmetric 1,2 bis(phosphino)ethanes with different phosphino groups were obtained by using our catalytic systems. The structures of the obtained vinylphosphine, unsymmetric 1,2 bis(phosphino)ethane, and iron catalyst precursors were confirmed by single crystal X-ray diffraction studies. PMID- 26805628 TI - Involvement of MicroRNA-210 Demethylation in Steroid-associated Osteonecrosis of the Femoral Head. AB - Angiogenesis is an important event in steroid-associated osteonecrosis of the femoral head (SONFH). Here we performed miRNA microarray with SONFH tissues (ONs) and the adjacent normal tissues (NLs) to select the angiogenic miRNA. The results showed that miR-210 was differentially expressed in SONFH versus normal tissues. Unexpectedly, its specific transcription factor, hypoxia-inducible factor-1alpha, was shown of no significant changes in ONs compared with NLs. Further Bisulfite sequencing revealed that miR-210 is embedded in a CpG island and miR-210 gene has 2 CpG sites with lower methylation percentage in ONs compared with NLs. Additionally, ONs with lower miR-210 gene methylation exhibited higher miR-210 expression. Next, we found that the endothelial cells treated with demethylating agents could significantly increase the expression of miR-210, along with promoted cell viability and differentiation. Some angiogenic genes (VEGF, bFGF, TNF-alpha and PCNA) were up-regulated as well. In addition, the supernatant of the cells after demethylation treatment displayed an enhanced ability of recruiting new microvessels in vivo. Taken together, our study not only provides novel insights into the regulation of angiogenesis in this disease, but also reveals a therapeutic opportunity for treatment of SONFH patients with demethylating agents. PMID- 26805629 TI - Enhanced isolation of lymphoid cells from human skin. AB - Studying skin immune cells under various pathophysiological conditions is vital for understanding the nature of cutaneous inflammatory responses. Available methods of isolating cells from the skin have relatively low yield or require in vitro culture. To increase the effective isolation of skin immune cells, we used collagenase P treatment. The number of T cells obtained ex vivo using this technique was dramatically greater than that obtained with conventional methods, without the need for long-term culture. The phenotype and function of isolated cells were comparable with those of cells isolated by EDTA treatment. Collagenase P-based methods will enhance the ability to investigate lymphoid cell function in both healthy and diseased skin. PMID- 26805631 TI - Large Brunner's gland hamartoma with annular stricture causing gastric outlet obstruction. PMID- 26805632 TI - Wernicke encephalopathy as initial presentation of lymphoma. PMID- 26805633 TI - Bleeding complications in critically ill patients with liver cirrhosis. AB - BACKGROUND/AIMS: Patients with liver cirrhosis (LC) are at risk for critical events leading to Intensive Care Unit (ICU) admission. Coagulopathy in cirrhotic patients is complex and can lead to bleeding as well as thrombosis. The aim of this study was to investigate bleeding complications in critically ill patients with LC admitted to a medical ICU (MICU). METHODS: All adult patients admitted to our MICU with a diagnosis of LC from January 2006 to December 2012 were retrospectively assessed. Patients with major bleeding at the time of MICU admission were excluded from the analysis. RESULTS: A total of 205 patients were included in the analysis. The median patient age was 62 years, and 69.3% of the patients were male. The most common reason for MICU admission was acute respiratory failure (45.4%), followed by sepsis (27.3%). Major bleeding occurred in 25 patients (12.2%). The gastrointestinal tract was the most common site of bleeding (64%), followed by the respiratory tract (20%). In a multivariate analysis, a low platelet count at MICU admission (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99) and sepsis (OR, 8.35; 95% CI, 1.04 to 67.05) were independent risk factors for major bleeding. The ICU fatality rate was significantly greater among patients with major bleeding (84.0% vs. 58.9%, respectively; p = 0.015). CONCLUSIONS: Major bleeding occurred in 12.2% of critically ill cirrhotic patients admitted to the MICU. A low platelet count at MICU admission and sepsis were associated with an increased risk of major bleeding during the MICU stay. Further study is needed to better understand hemostasis in critically ill patients with LC. PMID- 26805635 TI - Dysregulation of granulosal bone morphogenetic protein receptor 1B density is associated with reduced ovarian reserve and the age-related decline in human fertility. AB - Reproductive ageing is linked to the depletion of ovarian primordial follicles, which causes an irreversible change to ovarian cellular function and the capacity to reproduce. The current study aimed to profile the expression of bone morphogenetic protein receptor, (BMPR1B) in 53 IVF patients exhibiting different degrees of primordial follicle depletion. The granulosa cell receptor density was measured in 403 follicles via flow cytometry. A decline in BMPR1B density occurred at the time of dominant follicle selection and during the terminal stage of folliculogenesis in the 23-30 y good ovarian reserve patients. The 40+ y poor ovarian reserve patients experienced a reversal of this pattern. The results demonstrate an association between age-induced depletion of the ovarian reserve and BMPR1B receptor density at the two critical time points of dominant follicle selection and pre-ovulatory follicle maturation. Dysregulation of BMP receptor signalling may inhibit the normal steroidogenic differentiation required for maturation in older patients. PMID- 26805634 TI - Tadalafil reduces visceral adipose tissue accumulation by promoting preadipocytes differentiation towards a metabolically healthy phenotype: Studies in rabbits. AB - Development of metabolically healthy adipocytes within dysfunctional adipose tissue may represent an attractive way to counteract metabolic syndrome (MetS). In an experimental animal model of high fat diet (HFD)-induced MetS, in vivo, long- and short-term tadalafil treatments were able to reduce visceral adipose tissue (VAT) accumulation and hypertriglyceridemia, and to induce the expression in VAT of the brown fat-specific marker, uncoupling protein 1 (UCP1). VAT preadipocytes (PAD), isolated from the tadalafil-treated HFD rabbits, showed: i) a multilocular morphology; ii) an increased expression of brown fat-specific genes (such as UCP1 and CIDEA); iii) improved mitochondrial structure and dynamic and reduced superoxide production; iv) improved insulin sensitivity. Similar effects were obtained after in vitro tadalafil treatment in HFD rPAD. In conclusion, tadalafil counteracted HFD-associated VAT alterations, by restoring insulin-sensitivity and prompting preadipocytes differentiation towards a metabolically healthy phenotype. PMID- 26805636 TI - High VEGF serum values are associated with locoregional spread of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). AB - Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are highly vascularized neoplasms, capable of synthethisizing VEGF-A, a key mediator of angiogenesis. In pancreatic neuroendocrine tumors (pNETs) VEGF expression is higher in benign and low-grade tumors and associated with good prognosis (neuroendocrine paradox) while the VEGF role in gastrointestinal NETs (GI-NETs) is still unclear. In this study, we examined the VEGF-1154A/G polymorphism in 145 GEP-NET patients and 150 controls. Next, we measured VEGF serum levels and VEGF tumor protein expression, comparing it with Ki67 and tumor grade. Patients' VEGF serum levels were compared with VEGF -1145A/G genotypes and metastatic status as well as with chromogranin A (CgA) and 5-hydroxyindolacetic acid (5-HIAA) in case of GI-NET patients. In this study GEP-NET patients had elevated VEGF serum values when compared to healthy controls (p = 0.0013). VEGF-1145G allele correlated with higher VEGF serum levels (p = 0.002). Patients with metastatic tumors had higher VEGF serum values when compared to patients without metastases (p = 0.033), and highest levels were observed in case of lymph node metastases (p = 0.008). VEGF-1145G allele was more frequent in non-functional GI-NET patients than in healthy controls (p = 0.041). CgA was superior to VEGF in tumor detection, while VEGF was superior to 5-HIAA. A correlation was observed between VEGF immunohistochemical staining and Ki-67 (p = 0.028). Tumours with weaker VEGF protein expression were more aggressive than tumours with stronger VEGF expression, confirming a "neuroendocrine paradox" in GI-NETs. Our results suggest the role of VEGF in GI-NETs locoregional spread. PMID- 26805638 TI - [Facing our knowledge for improving patient care]. PMID- 26805639 TI - [Dialysis in the elderly, daily support]. PMID- 26805640 TI - [Diagnosis and management of chronic renal failure in the elderly]. AB - The incidence of chronic renal failure in the elderly is rising due to the ageing of the general population. Its management, and notably nephroprotective therapies, must be adapted to the elderly person who is often frail and with multiple pathologies. The decision to start extra-renal purification does not depend on the patient's chronological age but on their physiological age and requires dialogue between the patient and their family, the geriatrician and the nephrologist. PMID- 26805641 TI - [Peritoneal dialysis today and tomorrow]. AB - Peritoneal dialysis was first used in the 1980s. Less well-known than haemodialysis, it represents an important treatment option for elderly patients at home. PMID- 26805642 TI - [The support of the elderly person on hemodialysis]. AB - The ageing of the population is associated with an increase in the incidence of chronic renal failure. Management of the condition must be adapted to the specificities linked to ageing. With end-stage renal failure, haemodialysis is a substitution technique offered under certain conditions. The central role of the caregivers is to support and guide the elderly person along their care pathway. Faced with a reduced life expectancy, the aim of all concerned is to strike a balance between an effective treatment and quality of life. PMID- 26805643 TI - [Hemodialysis, sociological analysis of caregivers and patients]. AB - The trajectory of elderly patients undergoing haemodialysis is different from that of younger patients. A detailed description of these trajectories has resulted in the identification of certain characteristics inherent to the elderly. A study suggests moving beyond the perceptual knowledge of the professional in order to objectify the factors influencing these interpersonal relationships. PMID- 26805644 TI - [The diet of the elderly person undergoing dialysis]. AB - The elderly patient undergoing dialysis is often at risk of undernutrition. The condition may already be present at the pre-dialysis stage and can worsen once dialysis starts. Aside from the impact on the patient's quality of life and general health status, undernutrition exposes them to serious risk of complications and can be life-threatening. It is therefore essential that it is diagnosed early. PMID- 26805645 TI - ["I believe that dialysis has improved my health status"]. AB - For JM, dialysis is not a battle but a life contract which requires a time of adaptation both on a physical as well as an organisational level. After a few months of treatment, he describes here in simple terms how he feels about this new and unknown world, one which he is getting to grips with little by little thanks to the confidence he has in the professionals surrounding with him. PMID- 26805646 TI - [Anorexia and refusal to eat in the elderly]. AB - The question of the links between anorexia and the refusal to eat in the elderly is often the cause of major difficulties with regard to therapeutic strategies within caregiving teams. Likewise, few studies have been carried out into the diachronic links between teenage anorexia and that of the elderly. The role of the multi-disciplinary team is essential. PMID- 26805647 TI - [Orthostatic hypotension in elderly: a case-control study]. AB - Orthostatic hypotension is common in the elderly and is often associated with increased morbidity and mortality. Compression bandages are recommended as a first-line treatment but there is little evidence of their efficacy in literature. A case-control study involving 52 patients was carried out to test the efficacy of the bandages. In the group with orthostatic hypotension, compression improved the symptoms without correcting the blood pressure readings. PMID- 26805648 TI - [Falls, balance, and the future]. PMID- 26805649 TI - [Acute pain in the elderly]. PMID- 26805651 TI - Interim Prosthesis Options for Dental Implants. AB - Dental implants have become a popular treatment modality for replacing missing teeth. In this regard, the importance of restoring patients with function during the implant healing period has grown in recent decades. Esthetic concerns, especially in the anterior region of the maxilla, should also be considered until the definitive restoration is delivered. Another indication for such restorations is maintenance of the space required for esthetic and functional definitive restorations in cases where the implant site is surrounded by natural teeth. Numerous articles have described different types of interim prostheses and their fabrication techniques. This article aims to briefly discuss all types of implant related interim prostheses by different classification including provisional timing (before implant placement, after implant placement in unloading and loading periods), materials, and techniques used for making the restorations, the type of interim prosthesis retention, and definitive restoration. Furthermore, the abutment torque for such restorations and methods for transferring the soft tissue from interim to definitive prostheses are addressed. PMID- 26805650 TI - Lactose-modified DNA tile nanostructures as drug carriers. AB - BACKGROUND: DNA hybridization allows the preparation of nanoscale DNA structures with desired shape and size. DNA structures using simple base pairing can be used for the delivery of drug molecules into the cells. Since DNA carries multiple negative charges, their cellular uptake efficiency is low. Thus, the modification of the DNA structures with molecules that may enhance the cellular internalization may be an option. OBJECTIVE: The objective of this study is to construct DNA-based nanocarrier system and to investigate the cellular uptake of DNA tile with/without lactose modification. METHODS: Doxorubicin was intercalated to DNA tile and cellular uptake of drug-loaded DNA-based carrier with/without lactose modification was investigated in vitro. HeLa, BT-474, and MDA-MB-231 cancer cells were used for cellular uptake studies and cytotoxicity assays. Using fluorescence spectroscopy, flow cytometry, and confocal microscopy, cellular uptake behavior of DNA tile was investigated. The cytotoxicity of DNA tile structures was determined with WST-1 assay. RESULTS: The results show that modification with lactose effectively increases the intracellular uptake of doxorubicin loaded DNA tile structure by cancer cells compared with the unmodified DNA tile. CONCLUSION: The findings of this study suggest that DNA based nanostructures modified with carbohydrates can be used as suitable multifunctional nanocarriers with simple chemical modifications. PMID- 26805652 TI - Design of multi-shell Fe2O3@MnO(x)@CNTs for the selective catalytic reduction of NO with NH3: improvement of catalytic activity and SO2 tolerance. AB - Manganese based catalysts are highly active in the NH3-SCR reaction for NOx removal. Unfortunately, manganese oxides can be easily deactivated by sulfur dioxide in the flow gas, which has become the main obstacle for their practical applications. To address this problem, we presented a green and facile method for the synthesis of multi-shell Fe2O3@MnOx@CNTs. The morphology and structural properties of the catalysts were systematically investigated. The results revealed that the MnOx@CNT core-shell structure was formed during the chemical bath deposition, while the outermost MnOx species were transformed to Fe2O3 after the galvanic replacement reaction. The formation of the multi-shell structure induced the enhancement of the active oxygen species, reducible species as well as adsorption of the reactants, which brought about excellent de-NOx performance. Moreover, the Fe2O3 shell could effectively suppress the formation of the surface sulfate species, leading to the desirable SO2 resistance to the multi-shell catalyst. Hence, the synthesis protocol could provide guidance for the preparation and elevation of manganese based catalysts. PMID- 26805654 TI - Social functioning and facial expression recognition in children with neurofibromatosis type 1. AB - BACKGROUND: This study examined social functioning and facial expression recognition (FER) in children with neurofibromatosis type 1 (NF1) compared to typically developing peers. Specifically, the current research aimed to identify hypothesised relationships between neurocognitive ability, FER and social functioning. METHOD: Children, ages 8 to 16, with NF1 (n = 23) and typically developing peers (n = 23) were recruited during regularly scheduled clinic visits and through advertisements on an institutional clinical trials website, respectively. Participants completed a measure of FER, an abbreviated intelligence test and questionnaires regarding their quality of life and behavioural functioning. Parents were also asked to complete questionnaires regarding the social-emotional and cognitive functioning of their child. RESULTS: As expected, there were significant differences between children with NF1 and typically developing peers across domains of social functioning and FER. Within the sample of children with NF1, there were no significant associations observed between cognitive measures, social functioning and facial recognition skills. CONCLUSION: Children with NF1 exhibited high rates of social impairment and weak FER skills compared to controls. The absence of associations between FER with cognitive and social variables, however, suggests something unique about this skill in children with NF1. Theoretical comparisons are made to children with autism spectrum disorders, as this condition may serve as a potentially useful model in better understanding FER in children with NF1. PMID- 26805655 TI - Narrative information obtained during student selection predicts problematic study behavior. AB - INTRODUCTION: Up to now, student selection for medical schools is merely used to decide which applicants will be admitted. We investigated whether narrative information obtained during multiple mini-interviews (MMIs) can also be used to predict problematic study behavior. METHODS: A retrospective exploratory study was performed on students who were selected into a four-year research master's program Physician-Clinical Investigator in 2007 and 2008 (n = 60). First, counselors were asked for the most prevalent non-cognitive problems among their students. Second, MMI notes were analyzed to identify potential indicators for these problems. Third, a case-control study was performed to investigate the association between students exhibiting the non-cognitive problems and the presence of indicators for these problems in their MMI notes. RESULTS: The most prevalent non-cognitive problems concerned planning and self-reflection. Potential indicators for these problems were identified in randomly chosen MMI notes. The case-control analysis demonstrated a significant association between indicators in the notes and actual planning problems (odds ratio: 9.33, p = 0.003). No such evidence was found for self-reflection-related problems (odds ratio: 1.39, p = 0.68). CONCLUSIONS: Narrative information obtained during MMIs contains predictive indicators for planning-related problems during study. This information would be useful for early identification of students-at-risk, which would enable focused counseling and interventions to improve their academic achievement. PMID- 26805653 TI - Ethanol-induced GABAA receptor alpha4 subunit plasticity involves phosphorylation and neuroactive steroids. AB - GABAA receptors containing alpha4 subunits are widely implicated in acute ethanol sensitivity, and their spatial and temporal regulation prominently contributes to ethanol-induced neuroplasticity in hippocampus and cortex. However, it is unknown if alpha4-containing GABAA receptors in the thalamus, an area of high alpha4 expression, display similar regulatory patterns following ethanol administration, and if so, by which molecular mechanisms. In the current study, thalamic GABAA receptor alpha4 subunit levels were increased following a 6-week-, but not a 2 week chronic ethanol diet. Following acute high-dose ethanol administration, thalamic GABAA receptor alpha4 subunit levels were regulated in a temporal fashion, as a decrease was observed at 2h followed by a delayed transient increase. PKCgamma and PKCdelta levels paralleled alpha4 temporal expression patterns following ethanol exposure. Initial decreases in alpha4 subunit expression were associated with reduced serine phosphorylation. Delayed increases in expression were not associated with a change in phosphorylation state, but were prevented by inhibiting neuroactive steroid production with the 5alpha reductase inhibitor finasteride. Overall, these studies indicate that thalamic GABAA receptor alpha4 subunit expression following acute and chronic ethanol administration exhibits similar regulatory patterns as other regions and that transient expression patterns following acute exposure in vivo are likely dependent on both subunit phosphorylation state and neuroactive steroids. PMID- 26805656 TI - Effects of Soluble Lignin on the Formic Acid-Catalyzed Formation of Furfural: A Case Study for the Upgrading of Hemicellulose. AB - A comprehensive study is presented on the conversion of hemicellulose sugars in liquors obtained from the fractionation of Miscanthus, spruce bark, sawdust, and hemp by using formic acid. Experimental tests with varying temperature (130-170 degrees C), formic acid concentration (10-80 wt%), carbohydrate concentrations, and lignin separation were carried out, and experimental data were compared with predictions obtained by reaction kinetics developed in a previous study. The conversions of xylose and arabinose into furfural were inherently affected by the presence of polymeric soluble lignin, decreasing the maximum furfural yields observed experimentally by up to 24%. These results were also confirmed in synthetic mixtures of pentoses with Miscanthus and commercial alkali lignin. This observation was attributed to side reactions involving intermediate stable sugar species reacting with solubilized lignin during the conversion of xylose into furfural. PMID- 26805657 TI - Relation of Aortic Valve Morphologic Characteristics to Aortic Valve Insufficiency and Residual Stenosis in Children With Congenital Aortic Stenosis Undergoing Balloon Valvuloplasty. AB - Aortic valve morphology has been invoked as intrinsic to outcomes of balloon aortic valvuloplasty (BAV) for congenital aortic valve stenosis. We sought to use aortic valve morphologic features to discriminate between valves that respond favorably or unfavorably to BAV, using aortic insufficiency (AI) as the primary outcome. All patients who underwent BAV at 2 large-volume pediatric centers from 2007 to 2014 were reviewed. Morphologic features assessed on pre-BAV echo included valve pattern (unicuspid, functional bicuspid, and true bicuspid), leaflet fusion length, leaflet excursion angle, and aortic valve opening area and on post-BAV echo included leaflet versus commissural tear. Primary end point was increase in AI (AI+) of >=2 degrees . Eighty-nine patients (median age 0.2 years) were included in the study (39 unicuspid, 41 functional bicuspid, and 9 true bicuspid valves). Unicuspid valves had a lower opening area (p <0.01) and greater fusion length (p = 0.01) compared with functional and true bicuspid valves. Valve gradient pre-BAV and post-BAV were not different among valve patterns. Of the 16 patients (18%) with AI+, 14 had leaflet tears (odds ratio 13.9, 3.8 to 50). True bicuspid valves had the highest rate (33%) of AI+. On multivariate analysis, leaflet tears were associated with AI+, with larger opening area pre-BAV and lower fusion length pre-BAV. AI+ was associated with larger pre-BAV opening area. Gradient relief was associated with reduced angle of excursion. Valve morphology influences outcomes after BAV. Valves with lesser fusion and larger valve openings have higher rates of leaflet tears which in turn are associated with AI. PMID- 26805658 TI - Effect of Discontinuation of Prednisolone Therapy on Risk of Cardiac Mortality Associated With Worsening Left Ventricular Dysfunction in Cardiac Sarcoidosis. AB - Prednisolone (PSL) therapy is the gold standard treatment in patients with cardiac sarcoidosis (CS). However, clinicians often have difficulty in deciding whether to discontinue PSL therapy in long-term management. Sixty-one consecutive patients with CS were divided into 2 groups based on the discontinuation of PSL during the median follow-up period of 9.9 years. PSL was discontinued in 12 patients because of improvement of clinical findings. There were no significant differences between the 2 groups in age, gender, left ventricular ejection fraction (LVEF), findings of imaging techniques, incidence of fatal arrhythmias and heart failure, and dose of PSL. After discontinuation of PSL, 5 patients had cardiac death, and discontinuation of PSL was significantly associated with higher cardiac mortality compared with continuation (p = 0.035). Although patients with discontinuation had improvement of LVEF after PSL treatment, LVEF decreased after discontinuation of PSL. Furthermore, discontinuation of PSL was associated with greater percent decrease in LVEF compared with continuation (p = 0.037) during the follow-up period. In conclusion, in the long-term management of patients with CS, discontinuation of PSL was associated with poor clinical outcomes and decreased LVEF, suggesting the importance of PSL maintenance therapy. PMID- 26805659 TI - Usefulness of Low Cardiac Index to Predict Sleep-Disordered Breathing in Chronic Thromboembolic Pulmonary Hypertension. AB - Patients with chronic thromboembolic pulmonary hypertension (CTEPH) often have substantial right ventricular dysfunction. The resulting low cardiac index might predispose to sleep disordered breathing (SDB) by increasing ventilatory instability. The prevalence of SDB and potential association with impaired cardiac index was examined in patients with CTEPH. Patients referred for evaluation for pulmonary thromboendarterectomy surgery were recruited. Subjects underwent a sleep study, unless already using positive airway pressure therapy. Hemodynamic data were obtained from contemporaneous right-sided cardiac catheterization. A total of 49 subjects were included. SDB-defined as ongoing positive airway pressure use or apnea-hypopnea index (AHI) >=5/h-was found in 57% of subjects. SDB was generally mild in severity, with respiratory events mainly consisting of hypopneas. Cardiac index was found to be significantly lower in subjects with SDB than those without (2.19 vs 2.55 L/min/m(2); p = 0.024), whereas no differences were observed in other characteristics. Additionally, cardiac index was independently predictive of AHI. In a subgroup of subjects with an elevated percentage of central events, both cardiac index and lung to finger circulation time correlated with AHI. In conclusion, SDB is prevalent in patients with CTEPH and might decrease with treatments that improve cardiac index. PMID- 26805660 TI - Usefulness of Plasma Matrix Metalloproteinase-3 Levels to Predict Myocardial Infarction in Men With and Without Acute Coronary Syndrome. AB - Matrix metalloproteinase-3 (MMP-3), or stromelysin-1, is a matrix metalloproteinase which is expressed in atherosclerotic plaques and which has been implicated in the pathogenesis of acute coronary syndrome (ACS). Functional polymorphisms in the promoter region of the human MMP-3 gene resulting in an increased expression of MMP-3 have been shown to predict the risk of incident myocardial infarction (MI). However, there have been no studies that have specifically examined the utility of baseline plasma MMP-3 levels for the prediction of long-term MI. In this study, baseline plasma MMP-3 levels were measured in 355 male patients who were referred for coronary angiography and followed prospectively for the development of enzymatically confirmed MI out to 5 years. After adjustment for a variety of baseline clinical, angiographic, and laboratory parameters, plasma MMP-3 levels were an independent predictor of MI at 5 years (hazards ratio 1.42, 95% CI 1.13 to 1.79; p = 0.0023). Furthermore, in 5 additional multivariate models that included a variety of contemporary biomarkers associated with adverse outcomes and MI, MMP-3 remained an independent predictor of MI at 5 years. Similar results were obtained when the analyses were restricted to the subpopulation of patients presenting with ACS. In conclusion, elevated levels of MMP-3 are associated with an increased risk of long-term MI in patients with and without ACS referred for coronary angiography. Furthermore, this association is independent of a variety of clinical, angiographic, laboratory variables, including biomarkers with established prognostic efficacy for the prediction of MI. PMID- 26805661 TI - Reply. PMID- 26805662 TI - Relation of Elevated Heart Rate in Patients With Heart Failure With Reduced Ejection Fraction to One-Year Outcomes and Costs. AB - There are limited data describing outcomes associated with an elevated heart rate in patients with heart failure with reduced ejection fraction (HFrEF) in routine clinical practice. We identified patients with HFrEF at Duke University Hospital undergoing echocardiograms and heart rate assessments without paced rhythms or atrial fibrillation. Outcomes (all-cause mortality or hospitalization and medical costs per day alive) were assessed using electronic medical records, hospital cost accounting data, and national death records. Patients were stratified by heart rate (<70 and >=70 beats/min) and compared using generalized linear models specified with gamma error distributions and log links for costs and proportional hazard models for mortality/hospitalization. Of 722 eligible patients, 582 patients (81%) were treated with beta blockers. The median heart rate was 81 beats/min (25th and 75th percentiles 69 to 96) and 527 patients (73%) had a heart rate >=70 beats/min. After multivariate adjustment, a heart rate >=70 beats/min was associated with increased 1-year all-cause mortality or hospitalization, hazard ratio 1.37 (95% CI 1.07 to 1.75) and increased medical costs per day alive, cost ratio 2.03 (95% CI 1.53 to 2.69). In conclusion, at a large tertiary care center, despite broad use of beta blockers, a heart rate >=70 beats/min was observed in 73% of patients with HFrEF and associated with worse 1-year outcomes and increased direct medical costs per day alive. PMID- 26805664 TI - Non-fluoroscopic navigation systems for radiofrequency catheter ablation for supraventricular tachycardia reduce ionising radiation exposure. AB - INTRODUCTION: The use of non-fluoroscopic systems (NFS) to guide radiofrequency catheter ablation (RFCA) for the treatment of supraventricular tachycardia (SVT) is associated with lower radiation exposure. This study aimed to determine if NFS reduces fluoroscopy time, radiation dose and procedure time. METHODS: We prospectively enrolled patients undergoing RFCA for SVT. NFS included EnSiteTM NavXTM or CARTO(r) mapping. We compared procedure and fluoroscopy times, and radiation exposure between NFS and conventional fluoroscopy (CF) cohorts. Procedural success, complications and one-year success rates were reported. RESULTS: A total of 200 patients over 27 months were included and RFCA was guided by NFS for 79 patients; those with atrioventricular nodal reentrant tachycardia (AVNRT), left-sided atrioventricular reentrant tachycardia (AVRT) and right-sided AVRT were included (n = 101, 63 and 36, respectively). Fluoroscopy times were significantly lower with NFS than with CF (10.8 +/- 11.1 minutes vs. 32.0 +/- 27.5 minutes; p < 0.001). The mean fluoroscopic dose area product was also significantly reduced with NFS (NSF: 5,382 +/- 5,768 mGy*cm2 vs. CF: 21,070 +/- 23,311 mGy*cm2; p < 0.001); for all SVT subtypes. There was no significant reduction in procedure time, except for left-sided AVRT ablation (NFS: 79.2 minutes vs. CF: 116.4 minutes; p = 0.001). Procedural success rates were comparable (NFS: 97.5% vs. CF: 98.3%) and at one-year follow-up, there was no significant difference in the recurrence rates (NFS: 5.2% vs. CF: 4.2%). No clinically significant complications were observed in both groups. CONCLUSION: The use of NFS for RFCA for SVT is safe, with significantly reduced radiation dose and fluoroscopy time. PMID- 26805665 TI - First experience with robotic spleen-saving, vessel-preserving distal pancreatectomy in Singapore: a report of three consecutive cases. AB - INTRODUCTION: The use of laparoscopic distal pancreatectomy (LDP) has increased worldwide due to the reported advantages associated with this minimally invasive procedure. However, widespread adoption is hindered by its technical complexity. Robotic distal pancreatectomy (RDP) was introduced to overcome this limitation, but worldwide experience with RDP is still lacking. There is presently evidence that RDP is associated with decreased conversion rate and increased splenic preservation as compared to LDP. METHODS: We conducted a prospective study on our initial experience with robotic spleen-saving, vessel-preserving distal pancreatectomy (SSVP-DP) between July 2013 and April 2014. RESULTS: Three consecutive patients underwent attempted robotic SSVP-DP. The indications were a 2.1-cm indeterminate cystic neoplasm, 4.5-cm solid pseudopapillary neoplasm and 1.2-cm pancreatic neuroendocrine tumour. For all three patients, the procedure was completed without conversion, and the spleen, with its main vessels, was successfully conserved. The median total operation time, blood loss and postoperative stay were 350 (range 300-540) minutes, 200 (range 50-300) mL and 7 (range 6-14) days, respectively. Two patients had minor Clavien-Dindo Grade I complications (one Grade A pancreatic fistula and one postoperative ileus). One patient had a Clavien-Dindo Grade IIIa complication (Grade B pancreatic fistula requiring percutaneous drainage). All patients were well at the time of reporting after at least six months of follow-up. CONCLUSION: Our preliminary experience with robotic SSVP-DP confirmed the feasibility of the procedure. PMID- 26805666 TI - An evaluation of factors affecting adherence to antiepileptic drugs in patients with epilepsy: a cross-sectional study. AB - INTRODUCTION: Adherence to antiepileptic drug (AED) therapy is important for controlling seizures in patients with epilepsy (PWE). It is vital to identify the factors influencing adherence to AED therapy using validated tools. This study aimed to evaluate the pattern and extent of AED adherence among PWE and to identify the factors that influence adherence. METHODS: This was a cross sectional study involving PWE who had a confirmed diagnosis. Treatment adherence was assessed using the four-item Morisky Medication Adherence Scale. Univariate analysis with chi-square test was used to observe the association between different variables and AED adherence. Binary logistic regression analysis was used to identify the predictors of adherence. RESULTS: 451 PWE (mean age 27.3 +/- 8.1 years) were enrolled in the study; 251 (55.7%) were male and 198 (43.9%) were from the lower socioeconomic class. 326 (72.3%) patients had high adherence to AED therapy, while 125 (27.7%) had low adherence. AED adherence was significantly associated with socioeconomic status (p = 0.043) and type of epilepsy (p = 0.033). However, no significant difference was observed between adherence and age, gender, marital status, epilepsy duration, number and type of AEDs, and occurrence of adverse drug reactions. Patients with focal epilepsy and those from the middle/lower-middle socioeconomic classes were less likely to be nonadherent. The primary reason for nonadherence was forgetfulness. CONCLUSION: This study found that a majority of PWE have optimal rates of AED adherence and that forgetfulness is the primary reason for nonadherence among PWE. PMID- 26805667 TI - Utility of COX1 phylogenetics to differentiate between locally acquired and imported Plasmodium knowlesi infections in Singapore. AB - INTRODUCTION: Although there have been several phylogenetic studies on Plasmodium knowlesi (P. knowlesi), only cytochrome c oxidase subunit 1 (COX1) gene analysis has shown some geographical differentiation between the isolates of different countries. METHODS: Phylogenetic analysis of locally acquired P. knowlesi infections, based on circumsporozoite, small subunit ribosomal ribonucleic acid (SSU rRNA), merozoite surface protein 1 and COX1 gene targets, was performed. The results were compared with the published sequences of regional isolates from Malaysia and Thailand. RESULTS: Phylogenetic analysis of the circumsporozoite, SSU rRNA and merozoite surface protein 1 gene sequences for regional P. knowlesi isolates showed no obvious differentiation that could be attributed to their geographical origin. However, COX1 gene analysis showed that it was possible to differentiate between Singapore-acquired P. knowlesi infections and P. knowlesi infections from Peninsular Malaysia and Sarawak, Borneo, Malaysia. CONCLUSION: The ability to differentiate between locally acquired P. knowlesi infections and imported P. knowlesi infections has important utility for the monitoring of P. knowlesi malaria control programmes in Singapore. PMID- 26805668 TI - Understanding decisions leading to nonurgent visits to the paediatric emergency department: caregivers' perspectives. AB - INTRODUCTION: A significant percentage of paediatric emergency department (ED) attendances worldwide are nonurgent, adversely affecting patient outcomes and healthcare systems. This study aimed to understand the reasons behind nonurgent ED visits, in order to develop targeted and effective preventive interventions. METHODS: In-depth interviews were conducted with 49 caregivers to identify the decision-making factors related to taking children to the ED of KK Women's and Children's Hospital, Singapore. Interviews were carried out in the emergency room of the hospital after the children had been diagnosed with nonurgent conditions by the attending physician. Interview transcripts were analysed based on grounded theory principles. RESULTS: The demographics of our study cohort were representative of the target population. The main reasons given by the caregivers for attending paediatric EDs included perceived severity of the child's symptoms, availability of after-hours care, perceived advantage of a paediatric specialist hospital and mistrust of primary care physicians' ability to manage paediatric conditions. Insurance or welfare was a contributing factor for only a small portion of caregivers. CONCLUSION: The reasons provided by Singaporean caregivers for attending paediatric EDs were similar to those reported in studies conducted in Western countries. However, the former group had a unique understanding of the local healthcare system. The study's findings may be used to develop interventions to change the knowledge, attitudes and behaviours of caregivers in Singapore. PMID- 26805669 TI - Prevalence of asthma-like symptoms and assessment of lung function in schoolchildren born with low birth weight. AB - INTRODUCTION: This study aimed to determine the prevalence of asthma-like symptoms among schoolchildren with low birth weight (LBW), and to compare the lung function of these children with that of children with normal birth weight. METHODS: This was a comparative cross-sectional study. We recruited children aged 8-11 years from eight primary schools in Kota Bharu, Kelantan, Malaysia. The children were divided into two groups: those with LBW (< 2,500 g) and those with normal birth weight (>= 2,500 g). Parents of the enrolled children were asked to complete a translated version of the International Study of Asthma and Allergies in Childhood questionnaire. Lung function tests, done using a MicroLoop Spirometer, were performed for the children in both groups by a single investigator who was blinded to the children's birth weight. RESULTS: The prevalence of 'ever wheezed' among the children with LBW was 12.9%. This value was significantly higher than that of the children with normal birth weight (7.8%). Forced vital capacity (FVC), forced expiratory volume in one second, and forced expiratory flow when 50% and 75% of the FVC had been exhaled were significantly lower among the children with LBW as compared to the children with normal birth weight. CONCLUSION: LBW is associated with an increased prevalence of asthma-like symptoms and impaired lung function indices later in life. Children born with LBW may need additional follow-up so that future respiratory problems can be detected early. PMID- 26805670 TI - Cytotoxicity of a new antimicrobial coating for surgical screws: an in vivo study. AB - INTRODUCTION: The risk of surgery-related infection is a persistent problem in orthopaedics and infections involving implants are particularly difficult to treat. This study explored the responses of bone and soft tissue to antimicrobial coated screws. We investigated whether such screws, which have never been used to fix bony tissues, would result in a cytotoxic effect. We hypothesised that the coated screws would not be toxic to the bone and that the likelihood of infection would be reduced since bacteria are not able to grow on these screws. METHODS: Titanium screws were inserted into the left supracondylar femoral regions of 16 rabbits. The screws were either uncoated (control group, n = 8) or coated with a polyvinylpyrrolidone-polyurethane interpolymer with tertiary amine functional groups (experimental group, n = 8). At Week 6, histological samples were obtained and examined. The presence of necrosis, fibrosis and inflammation in the bony tissue and the tissue surrounding the screws was recorded. RESULTS: Live, cellular bone marrow was present in all the rabbits from the experimental group, but was replaced with connective tissue in four rabbits from the control group. Eight rabbits from the control group and two rabbits from the experimental group had necrosis in fatty bone marrow. Inflammation was observed in one rabbit from the experimental group and five rabbits from the control group. CONCLUSION: Titanium surgical screws coated with polyvinylpyrrolidone-polyurethane interpolymer were associated with less necrosis than standard uncoated screws. The coated screws were also not associated with any cytotoxic side effect. PMID- 26805671 TI - Human liver chimeric mice as a new model of chronic hepatitis E virus infection and preclinical drug evaluation. AB - BACKGROUND & AIMS: Hepatitis E virus (HEV) is a major cause of acute hepatitis as well as chronic infection in immunocompromised individuals; however, in vivo infection models are limited. The aim of this study was to establish a small animal model to improve our understanding of HEV replication mechanisms and permit the development of effective therapeutics. METHODS: UPA/SCID/beige mice repopulated with primary human hepatocytes were used for infection experiments with HEV genotype (GT) 1 and 3. Virological parameters were determined at the serological and intrahepatic level by real time PCR, immunohistochemistry and RNA in situ hybridization. RESULTS: Establishment of HEV infection was achieved after intravenous injection of stool-derived virions and following co-housing with HEV infected animals but not via inoculation of serum-derived HEV. GT 1 infection resulted in a rapid rise of viremia and high stable titres in serum, liver, bile and faeces of infected mice for more than 25 weeks. In contrast, viremia in GT 3 infected mice developed more slowly and displayed lower titres in all analysed tissues as compared to GT 1. HEV-infected human hepatocytes could be visualized using HEV ORF2 and ORF3 specific antibodies and HEV RNA in situ hybridization probes. Finally, six-week administration of ribavirin led to a strong reduction of viral replication in the serum and liver of GT 1 infected mice. CONCLUSION: We established an efficient model of HEV infection to test the efficacy of antiviral agents and to exploit mechanisms of HEV replication and interaction with human hepatocytes in vivo. PMID- 26805672 TI - Disentangling introspective and exteroceptive attentional control from emotional appraisal in depression using fMRI: A preliminary study. AB - The neurocognitive abnormalities in affective experience associated with depression remain incompletely understood. We examined BOLD activity in 10 healthy and 10 depressed subjects while they viewed emotional picture sets and categorized their experience in the moment as pleasant, unpleasant or neutral (introspective attention), as well as when they viewed matched pictures and judged whether they depicted indoor or outdoor scenes (exteroceptive attention). Contrasts permitted investigation of differences in neural activity between groups associated with (1) attentional control, and (2) appraisal of valence. Introspective attentional control (compared to exteroceptive attentional control) activated a common pregenual anterior cingulate (pACC) region in depressed and control subjects. Contrasts between appraised valences of attended emotional responses revealed a consistent pattern of increased BOLD activity to unpleasant emotional responses and decreased BOLD activity to pleasant emotional responses in depressed subjects relative to controls in ventromedial prefrontal cortex and insula. These findings support the conclusion that mechanisms for conscious attention to emotional experiences are intact in depressed subjects and that the affective disturbance in MDD is related to altered reactivity to pleasant vs. unpleasant stimuli. PMID- 26805674 TI - Lumbopleural Shunting as an Alternative Cerebrospinal Fluid Diversion Modality for Management of Idiopathic Intracranial Hypertension: Is It Time for a Change? PMID- 26805673 TI - Blister-Like Aneurysms: Report of Successful Surgical Treatment of Consecutive Cases and Review of the Literature. AB - INTRODUCTION: Blister-like aneurysms (BAs) are usually defined as arterial lesions arising from nonbranching sites on intracranial arteries. Because of specific peculiarities such as different pathophysiology, fragility of the aneurysmal wall, high risk of intraoperative bleeding, and high probability of losing parent vessel patency, their treatment is controversial, and both endovascular and surgical options have been reported. METHODS: From 2006 to 2015 (10 years), 7 aneurysms in 6 patients were treated. We retrospectively reviewed the records of these patients to analyze clinical pictures and outcomes, which are expressed as modified Rankin Score. RESULTS: In our sample of 7 aneurysms in 6 patients, all BAs were successfully treated (complete exclusion in 100% on follow-up angiography). A good outcome (modified Rankin Score = 0) was achieved in all patients, with no difference related to aneurysm size and location. There was no mortality. CONCLUSIONS: Surgical treatment of BAs may be effective and have acceptable complications and outcomes. PMID- 26805675 TI - Influence of Obesity on Access-Related Complications During Anterior Lumbar Spine Interbody Fusion. AB - OBJECTIVE: The anterior lumbar spine approach has gained in popularity in recent years, but the associated access-related complications for obese patients have not been clearly established. This study aimed to analyze the relationship between obesity or overweight and the safety of the anterior lumbar spine approach. METHODS: Eighty-four consecutive patients admitted for lumbar spine surgery by anterior approach between 2011 and 2014 were included. The surgical approach consisted of left lateral minilaparotomy and retroperitoneal dissection. The patients were categorized into 3 different groups according to their body mass index (BMI). The studied outcomes measures included medical history, BMI, the number of fused levels, surgery duration, blood loss, vascular injury, day of discharge, surgical revision, and wound infection. RESULTS: No significant difference was found across the BMI groups with regard to vascular or infectious complications. The duration of surgery was significantly higher in the obese group. CONCLUSIONS: Because BMI does not seem to increase the overall risk of complications, the anterior lumbar spine approach should be considered in obese or overweight patients, as in nonoverweight patients. PMID- 26805676 TI - Splitting of the Optic Nerve by a Pituitary Macroadenoma. AB - BACKGROUND: Splitting of the optic nerve by a pituitary adenoma is an extremely unusual condition with only 3 cases reported to date. CASE DESCRIPTION: A 41-year old woman presented with visual loss as a result of an aggressive pituitary macroadenoma causing the splitting of the right optic nerve. Possible mechanisms of this condition are discussed, and the literature is reviewed. CONCLUSIONS: In aneurysm and tumor cases, awareness of the exact anatomy is particularly important to preserve function. An overlooked duplication or penetration of cranial nerves may result in inadvertent injury to important structures and loss of function. PMID- 26805677 TI - Sedation with alpha2 Agonist Dexmedetomidine During Unilateral Subthalamic Nucleus Deep Brain Stimulation: A Preliminary Report. AB - OBJECTIVE: The alpha2 agonist dexmedetomidine (DEX) is an anesthetic agent that can provide sedation and analgesia without respiratory depression or changes in neuronal activity during microrecordings. The aim of our study was to confirm the efficacy and safety of anesthesia with DEX for unilateral deep brain stimulation of the subthalamic nucleus (STN) in patients with Parkinson disease. METHODS: In 2013 and 2014, a series of 11 consecutive patients received continuous low-dose DEX infusion during unilateral deep brain stimulation of the STN. Intraoperative microrecordings, stimulation results, and patient reaction times in executing verbal and motor tasks were retrospectively analyzed. Functional outcomes were evaluated by comparing preoperative and 1-year postoperative Unified Parkinson's Disease Rating Scale Part III scores. RESULTS: Typical activity of the STN was recorded in all patients, and the delay in the execution of both motor and verbal tasks was <=2 seconds. No hemorrhagic complications occurred, and no postoperative side effects were observed. The mean percentage of Unified Parkinson's Disease Rating Scale Part III improvement at last follow-up was 39.01% (range, 23.70%-55.60%). The mean percentage of levodopa equivalent dose reduction was 45.86% (range, 21.50%-65.70%). CONCLUSIONS: The results of our study confirm that the use of DEX in managing patients with Parkinson disease during unilateral deep brain stimulation of the STN is safe and effective and can be considered a promising option for sedation during this type of procedure. PMID- 26805678 TI - Minimally Invasive Transsulcal Resection of Intraventricular and Periventricular Lesions Through a Tubular Retractor System: Multicentric Experience and Results. AB - BACKGROUND: Conventional approaches to deep-seated cerebral lesions range from biopsy to transcortical or transcallosal resection. Although the former does not reduce tumor burden, the latter are more invasive and associated with greater potential for irreparable injury to normal brain. Disconnection syndrome, hemiparesis, hemianesthesia, or aphasia is not uncommon after such surgery, especially when lesion is large. By contrast, the transsulcal parafascicular approach uses naturally existing corridors and a tubular retractor to minimize brain injury. METHODS: A retrospective review of patients undergoing minimally invasive transsulcal parafascicular resection of ventricular and periventricular lesions, across 5 independent centers, was conducted. RESULTS: Twenty patients with lesions located in the lateral ventricle (n = 9), the third ventricle (n = 6) and periventricular region (n = 4) are described in this report. Average age was 64 years (8 male/12 female). The average depth from cortical surface was 4.37 cm. A 13.5-mm-diameter tubular retractor (BrainPath [NICO Corporation, Indianapolis, Indiana, USA]) of differing lengths was used, aided by neuronavigation. Gross total resection was obtained in 17 patients. Pathologies included colloid cyst, subependymoma, glioma, meningioma, central neurocytoma, lymphoma, and metastasis. Three patients experienced transient morbidity: memory loss (2), hemiparesis (1). One patient died 3 months postoperatively as a result of unrelated pulmonary illness. Follow-up ranged from 6 to 27 months (average, 12 months). CONCLUSIONS: This technique is safe and effective for the treatment of intraventricular and periventricular lesions. Surgery-related morbidity is minimal and often transient. Lesions are satisfactorily resected and residuum occurs only when the neoplasm involves vital structures. The tubular retractor minimizes trauma to brain incident in the surgeon's path. PMID- 26805679 TI - Metastatic Gastrointestinal Stromal Tumor to the Skull. AB - BACKGROUND: Gastrointestinal stromal tumors (GISTs) arising from the interstitial cells of Cajal along the gastrointestinal tract rarely metastasize to the central nervous system (CNS) but require aggressive multimodal therapies when they do. We present a case of recurrent GIST metastasis to the skull and review the literature on management, including the role of molecular profiling in determining adjuvant treatment. CASE: A 64-year-old woman presented with an enlarging palpable mass over her right eye. Magnetic resonance imaging revealed an enhancing T1-hypointense, T2-hyperintense right frontal calvarial lesion with lytic features on computed tomography. Pathology confirmed metastatic GIST to the skull with dural involvement. Molecular profiling revealed a mutation in exon 11 of KIT in her primary tumor, while the skull metastasis harbored an additional mutation in exon 17 associated with acquired drug resistance. CONCLUSION: We review the epidemiology of GIST metastases and discuss potential reasons for its rare presentation to the CNS. Additionally, we highlight the diagnostic and prognostic value of molecular profiling for metastatic GIST, as well as its influence in arbitrating targeted molecular inhibitor therapy. Evolving molecular signatures, associated with treatment resistance, may play a pivotal role in future integration with multimodality treatment strategies for CNS GIST. PMID- 26805680 TI - Long-Term Causes of Death and Excess Mortality After Carotid Artery Ligation. AB - OBJECTIVE: Carotid artery ligation (CAL) is used to treat large and complex intracranial aneurysms. However, little is known about long-term survival and causes of death in patients who undergo the procedure. This study was intended to evaluate if patients who have undergone CAL have long-term excess mortality and what the causes of death are. METHODS: All patients were treated at Helsinki University Hospital between 1937 and 2009. Patients who had undergone CAL and survived >=1 year after the procedure were included in the cohort. Follow-up was until death or 2015 (2711 patient-years). Causes of death were reviewed and relative survival ratios calculated using the Ederer II method and a matched population. RESULTS: There was 12% excess mortality in all patients 20 years after CAL and 22% after 30 years. A higher proportion of the patients who had subarachnoid hemorrhage (SAH) died during follow-up compared with unruptured patients undergoing CAL. Cardiovascular disease and cerebrovascular accident were the leading causes of death. CONCLUSIONS: Patients with unruptured aneurysms did not experience as much excess mortality as those who had an SAH. The higher proportion of deaths observed in ruptured patients may be partly because of long term excess mortality conferred by the SAH itself or SAH risk factors. Although the entire population did display excess mortality compared with the general population, this may be because of shared risk factors for aneurysm development and rupture and the cause of death. PMID- 26805681 TI - Utility of Neuronavigation in Intracranial Meningioma Resection: A Single-Center Retrospective Study. AB - OBJECTIVE: In this study, we validate the utility of navigation in intracranial meningioma excision and evaluate the effectiveness of image guidance surgery based on clinical outcome, extent of resection, and recurrence-free survival (RFS). METHODS: Information related to clinical history, use of neuronavigation, neuroimaging, microsurgical dissection, and outcomes of 517 consecutive cases with meningiomas between January 1995 and June 2015 was collected retrospectively. A Cox proportional hazards regression model was used to determine independent predictors of RFS. RESULTS: In this study, overall recurrence rate after tumor excision with or without neuronavigation was 17.7% and 31.2%, respectively (P = 0.03). Based on neuronavigation use, RFS of the patients with meningiomas in different locations also varied significantly (skull base; with, 110 months vs. without, 157 months; P = 0.02). The median RFS for patients operated on with or without use of neuronavigation during resection of tumors was 167 and 97 months, respectively, (log-rank P =0.0001). In Cox regression multivariate analysis, use of neuronavigation (P = 0.0001), gross total resection (Simpson grade I-II; P = 0.001), and World Health Organization grade I tumor (P = 0.0001) were revealed as significant predictors of RFS. In addition, mean blood loss (P = 0.005) and average length of stay (P = 0.008) in the hospital were significantly reduced and performance status was improved using neuronavigation during resection of meningiomas. CONCLUSIONS: Interactive surgical navigation is a useful tool in the operative management of intracranial meningiomas to decrease recurrence rate, blood loss, and length of stay, and to improve RFS and performance status. Therefore, use of neuronavigation should be ensured during resection of intracranial meningiomas. PMID- 26805682 TI - Restenosis After Carotid Endarterectomy: Insight Into Risk Factors and Modification of Postoperative Management. AB - BACKGROUND: Restenosis after carotid endarterectomy (CEA) is a potential complication after surgery for carotid stenosis. Stroke after CEA is a debilitating complication secondary to restenosis, and modification of postoperative care may be necessary to decrease the incidence of postoperative stroke after CEA. We sought to identify the clinical and patient factors that are associated with this complication. METHODS: A retrospective analysis of all neurosurgical patients who underwent CEA for symptomatic or asymptomatic carotid stenosis was performed. Factors were compared against the outcome variable in a univariate analysis. A multivariate logistic regression model was used to identify independent predictive variables. We used Kaplan-Meier analysis to compare the effect of the variables on long-term event-free survival. RESULTS: A total of 273 CEA procedures and their outcomes were analyzed with a mean follow up of 50.7 months. Twenty-one patients had restenosis (7.6%). Rates of restenosis and restenosis-free survival were analyzed with Kaplan-Meier curves (log-rank test). In the multivariate model, a family history of stroke was the only variable that was significantly associated with restenosis after CEA. CONCLUSIONS: Our findings suggest that a family history of stroke is an important factor that predisposes patients to restenosis after CEA. Restenosis-free survival is influenced by the presence of hyperlipidemia, age, and family history of stroke. Closer surveillance with more frequent follow-up and multidisciplinary management may be beneficial in patients who have these risk factors to prevent restenosis and prolong restenosis-free survival. PMID- 26805683 TI - Microsurgical Resection for Persistent Arteriovenous Malformations Following Gamma Knife Radiosurgery: A Case-Control Study. AB - OBJECTIVE: To explore outcomes after microsurgery of brain arteriovenous malformations (AVMs) that failed to be obliterated by Gamma Knife radiosurgery (GKRS). METHODS: From January 2000 to January 2014, 42 consecutive patients underwent surgical resection of persistent AVMs after GKRS. These 42 patients with AVMs who underwent radiosurgery (radiosurgery group) were individually matched with 42 patients with AVMs who did not undergo radiosurgery (no radiosurgery group) based on patient and AVM characteristics. The modified Rankin Scale was used to assess neurologic status of patients. The effects of GKRS on AVM resection and surgical outcomes were analyzed. RESULTS: After GKRS, the mean AVM volume was significantly reduced by 76.8% (P < 0.01), the size was reduced by 41% (P < 0.01), and the Spetzler-Martin grade was reduced in 61.9% of the patients (P < 0.01). During the time interval from radiosurgery to surgical resection, subsequent hemorrhages led to significant neurologic deterioration (P = 0.046). Compared with the control group, the frequency of preoperative embolization, operative time, and blood loss were significantly lower in the radiosurgery group (all P < 0.05). The no radiosurgery group had a significantly higher rate of worsening in mRS scores at 6 months after surgery (40.5% vs. 16.7%, P = 0.029). Good neurologic status (mRS score <3) was achieved in 81% of the radiosurgery group and 83% of the no radiosurgery group at the final follow up evaluation. CONCLUSIONS: GKRS performed several years before microsurgical resection can facilitate resectability of AVMs and decrease the rate of postoperative neurologic deterioration. For patients with persistent AVMs several years after GKRS, microsurgical resection is recommended to achieve good clinical outcomes. PMID- 26805684 TI - Impact of Resecting Radiation Necrosis and Pseudoprogression on Survival of Patients with Glioblastoma. AB - INTRODUCTION: Radiation necrosis (RN) and pseudoprogression are known as postradiation treatment effects and may simulate tumor progression. The disease course of glioblastoma patients who had developed RN and the impact of resecting RN on survival have not been evaluated. This study examines the clinical course of patients considered candidates for repeat surgery for a recurring brain mass proven to be RN and compared these with patients who had true tumor recurrence at surgery. METHODS: Of 159 patients with glioblastoma who were reoperated on because of a presumed recurrent tumor requiring repeat surgery, 18 had RN as the major component of the resected mass. The characteristics and outcome of these 18 patients were retrospectively analyzed and compared with patients in whom active and bulky tumor was found during surgery. RESULTS: Radiation necrosis occurred significantly earlier than true tumor recurrence. Patients with RN harbored larger lesions and were significantly more symptomatic before the second surgery. Most patients with RN who underwent GTR of the lesion in the second operation experienced faster resolution of the surrounding edema compared with patients who underwent STR or biopsy only. There was no significant difference in survival between the 2 groups. CONCLUSIONS: These data provide an opportunity to examine the clinical course of a selected group of patients with histologically verified RN. Although RN is associated with more severe neurologic symptoms that improve after surgery, its occurrence or surgical removal carries no survival advantage compared with patients who undergo a repeat operation for true tumor recurrence. PMID- 26805685 TI - Predictors and Rates of Delayed Symptomatic Hyponatremia after Transsphenoidal Surgery: A Systematic Review [corrected]. AB - BACKGROUND: Delayed symptomatic hyponatremia (DSH) is a known complication of transsphenoidal surgery that can lead to prolonged hospital stay, readmission, and in rare cases, death. Many potential predictors for development of DSH have been investigated. A better understanding of DSH risk can lead to better patient outcomes. We performed a systematic review to determine the rates and predictors of DSH after both endoscopic transsphenoidal surgery and microscopic transsphenoidal surgery. METHODS: A systematic search of the literature was conducted using MEDLINE/PUBMED, EMBASE, and Cochrane databases. Inclusion criteria were 1) case series with at least 10 cases reported, 2) adult patients who underwent eTSS or mTSS for pituitary tumors, and 3) reported occurrence of DSH (defined as serum sodium level <135 mEq/L with associated symptoms) after postoperative day 3. Data were analyzed using CMA V.3 Statistical Software (2014). RESULTS: Ten case series satisfied the inclusion criteria for a total of 2947 patients. Various factors including age, gender, cerebrospinal fluid leak, and tumor size were investigated as potential predictors of DSH. DSH event rates for both mTSS and eTSS fell between around 4 and 12 percent and included a variety of proposed predictors. CONCLUSIONS: Age, gender, tumor size, rate of decline of blood sodium, and Cushing disease are potential predictors of DSH. By identifying patients at high risk for DSH, preventative efforts can be implemented in the perioperative setting to reduce the incidence of potentially catastrophic hyponatremia following transsphenoidal surgery. PMID- 26805686 TI - A Case of Complete Resolution of Hemiballismus After Carotid Endarterectomy. AB - BACKGROUND: Hemiballismus is a rare presentation of symptomatic carotid stenosis that is underreported in the neurosurgical literature. It is characterized by severe large-amplitude movements that are classically caused by lesions of the subthalamic nucleus. Given the arterial border zone position of the subthalamic nucleus between the anterior and posterior circulation, hemodynamically compromising carotid stenosis can lead to hypoperfusion in this location. CASE DESCRIPTION: We describe the case of a patient who presented with acute-onset hemiballismus that had complete resolution of symptoms after carotid endarterectomy. CONCLUSIONS: We suggest that neurovascular imaging should be part of the initial workup of this condition and that prompt diagnosis and treatment of carotid artery stenosis in patients who present with new-onset hemiballismus are essential for reducing risk of imminent stroke. PMID- 26805687 TI - MiR-184 Regulates Proliferation in Nucleus Pulposus Cells by Targeting GAS1. AB - OBJECTIVE: The precise mechanism of nucleus pulposus proliferation in the degeneration of the intervertebral disk pathogenesis remains to be implicated. MicroRNAs (MiRNAs) are a class of 18-22 nucleotides, which are small, noncoding RNAs that inhibit protein translation by binding to the 3'-UTR of target gene. Recent studies have shown that miRNAs play a crucial role in various cell biologies such as cell proliferation, invasion, migration, and cell cycle. However, the role of miR-184 in nucleus pulposus proliferation is still unknown. METHOD: qRT-PCR was performed to measure the expression of miR-184. CCK-8 assay, qRT-PCR, and Western blot were used to measure the functional role of miR-184 in nucleus pulposus (NP) cells. Western blot and Luciferase assays were done to find the miR-184 target gene. RESULT: We demonstrated that expression of miR-184 was upregulated in degenerative NP tissues compared with that in the control NP tissues, and the expression of miR-184 was positively correlated with disk degeneration grade. We identified Growth Arrest Specific Gene 1 (GAS1) as a direct target gene of miR-184 in NP cells, and ectopic expression of miR-184 promoted NP cells proliferation. In addition, we found that GAS1 expression was downregulated in degenerative NP tissues compared with that in the control NP tissues and the GAS1 expression was inversely correlated with the grade of disk degeneration. Moreover, we demonstrated that miR-184 overexpression could induce AKT phosphorylation and ectopic expression of GAS1 decreased the miR-184 overexpressing NP cells proliferation. CONCLUSION: These results demonstrated that miR-184 and the GAS1/Akt pathway may be a potential therapeutic target for intervertebral disc degeneration. PMID- 26805688 TI - Cerebrospinal Fluid Infection Associated with Silver-Impregnated External Ventricular Drain Catheters. AB - OBJECTIVE: Silver-impregnated external ventricular drains (EVDs) have reduced the number of cases of ventriculitis. Risk factors for developing ventriculitis associated with plain EVD catheters have been well documented and incorporated into clinical practice, but risk factors in association with silver EVDs are unknown. Therefore, we sought to determine the risk factors for developing ventriculitis in patients with a silver EVD. METHODS: Prospectively collected data on consecutive patients undergoing insertion of a silver-impregnated EVD between October 2011 and September 2013 were analyzed. Cerebrospinal fluid (CSF) infection was defined as positive CSF microbiologic culture. Univariate and multivariate regression was performed to identify independent risk factors for CSF infection. RESULTS: There were 362 EVDs placed in 263 patients (142 women; median age 52 years; interquartile range, 40-62 years). There were 15 infections (6.4 per 1000 days of EVD drainage) recorded. Gram-negative organisms (8 of 15) were most commonly observed, although Staphylococcus was the most common genus (7 of 15; 46%) identified. Univariate analysis indicated that patients requiring EVD replacement (P < 0.0001), patients requiring bilateral EVDs (P < 0.0001), and patients with a CSF leak (P < 0.0001) were at increased risk of infection. Only need for EVD replacement remained significant on multivariate analysis (P < 0.0001, odds ratio = 15.9, confidence interval = 4.5-55.9). CONCLUSIONS: We identified an infection rate of 5.2% in this large contemporary series of patients undergoing silver EVD insertion according to a set protocol. These data suggest that targeting strategies to reduce Staphylococcus species is important, and increased vigilance for an increased incidence of gram-negative organisms is needed. Decreasing the need for EVD replacement is important in reducing infection rates further. PMID- 26805689 TI - Association of Steroid Use with Deep Venous Thrombosis and Pulmonary Embolism in Neurosurgical Patients: A National Database Analysis. AB - OBJECTIVE: Venous thromboembolism (VTE) is a major preventable cause of morbidity and mortality in hospitalized patients and is a widely accepted measure for quality of care. Prolonged corticosteroid therapy, which is common in neurosurgical patients, has been associated with VTE. Using a national database, we sought to determine whether corticosteroid use for >10 days was an independent risk factor for deep venous thrombosis (DVT) and pulmonary embolism (PE). METHODS: The well-validated American College of Surgeons National Surgical Quality Improvement Program database was queried to evaluate the rates of VTE during the period 2006-2013 in patients undergoing neurosurgical procedures. A multivariate regression model was constructed to assess the effect of prolonged corticosteroid use on the occurrence of PE and DVT by postoperative day 30. RESULTS: Of 94,620 patients identified, 565 (0.60%) developed PE and 1057 (1.12%) developed DVT within 30 days after surgery. In the multivariate model, patients receiving corticosteroids were significantly more likely to have PE (odds ratio = 1.47, 95% confidence interval = 1.13-1.90, P = 0.004) and DVT (odds ratio = 1.55, 95% confidence interval = 1.28-1.87, P < 0.001). Other factors independently associated with development of PE and DVT included the presence of malignancy, longer hospitalization, certain infections (including pneumonia and urinary tract infections), and stroke with a neurologic deficit. CONCLUSIONS: In the neurosurgical population, prolonged courses of corticosteroids are associated with an increased risk of developing postoperative DVT and PE, even when controlling for potential confounders. PMID- 26805690 TI - Risk Factors to Predict Postoperative Fever After Coil Embolization of Ruptured Intracranial Aneurysms. AB - OBJECTIVE: To investigate risk factors to predict postoperative fever after endovascular treatment of ruptured intracranial aneurysms. METHODS: Patients undergoing endovascular coiling to treat subarachnoid hemorrhage in Nantong University between November 2011 and September 2014 were retrospectively reviewed. Postoperative temperature and patient demographic data, admission status, characteristic features of aneurysms, and endovascular coiling procedure were documented and analyzed. There were 336 consecutive patients included in this study, and 111 were classified as febrile (tympanic temperature >38.3 degrees C for at least 2 consecutive days). RESULTS: Univariate analysis demonstrated that age, interval from onset of subarachnoid hemorrhage to operation, history of hypertension and smoking, Hunt and Hess grade, Fisher grade, temperature before coiling, leukocyte count on admission, and infectious complications were correlated with postoperative fever. Five variables were independent risk factors to predict fever by multivariate logistic regression: age >70 years (odds ratio [OR] = 2.6, 95% confidence interval [CI] = 1.2-5.6), Fisher grade 3 or 4 (OR = 2.2, 95% CI = 1.1-4.3), leukocyte count >10,000/mm(3) on admission (OR = 2.3, 95% CI = 1.3-4.0), temperature >37.5 degrees C before coiling (OR = 4.6, 95% CI = 2.0-10.7), and infectious complications (OR = 4.4, 95% CI = 2.2-8.6). CONCLUSIONS: Postoperative fever after coil embolization was predicted by changeable and unchangeable risk factors in subarachnoid hemorrhage. However, characteristic features of aneurysms and the coiling procedure had no impact on development of postoperative fever. Preventing any infectious complications, lowering temperature before embolization, and draining bloody cerebrospinal fluid may assist in the prevention of subsequent fever. PMID- 26805691 TI - Basic Principles of Hemodynamics and Cerebral Aneurysms. AB - BACKGROUND: Rupture is the most serious consequence of cerebral aneurysms, and its likelihood depends on nonmodifiable and modifiable risk factors. Recent efforts have focused on analyzing the effects of hemodynamic forces on the initiation, growth, and rupture of cerebral aneurysms. Studies of the role of hemodynamics in the physiopathology of intracranial aneurysms fall between mechanical engineering and molecular biology. METHODS: This review summarizes the basic principles of the effect of hemodynamic forces on the cerebral vascular wall. CONCLUSIONS: The size of the aneurysm dome is the most common parameter used in clinical practice to estimate the risk of rupture. However, relying only on aneurysm size means excessively simplifying a more complicated reality. Aneurysms emerge in areas of the vascular wall exposed to high wall shear stress. The direction in which blood flows once an aneurysm forms depends on aspects such as neck diameter, its angle with respect to the parent artery, the parent vessel caliber, the caliber or the angle of efferent vessels, and aneurysm shape. The progression and rupture of aneurysms have been associated with zones of the aneurysm wall exposed to both high and low wall shear stresses. Advances in this challenging and growing field are intended to predict more precisely the risk of rupture of aneurysms and to better understand the mechanisms of origin and growth of aneurysms. PMID- 26805692 TI - Intraoperative Supratentorial Extradural Hematoma Complicating Excision of a Giant Vestibular Schwannoma. AB - BACKGROUND: A man developed a rare and unexpected contralateral intraoperative complication during a translabyrinthine resection of a large cystic vestibular schwannoma. CASE DESCRIPTION: A 29-year-old man presented with progressive, low level right-sided tinnitus and hearing loss. Magnetic resonance imaging displayed a large multicystic lesion suggestive of a vestibular schwannoma extending into the right cerebellopontine angle and distorting the midbrain. The patient subsequently underwent translabyrinthine excision of the lesion. The operation was complicated by brain swelling that obscured the operative field. Cerebrospinal fluid drainage failed to improve operative conditions, and an urgent computed tomography scan was performed, which showed a large supratentorial extradural hematoma as the cause. This extradural collection was promptly evacuated, and the patient had a good neurologic recovery postoperatively. CONCLUSIONS: Although the development of postoperative extradural hematomas resulting from cerebrospinal fluid overdrainage is reported in the literature, this case is unique in that infratentorial surgery led to the development of a supratentorial hematoma. PMID- 26805693 TI - The Filum Terminale: A Cadaver Study of Anatomy, Histology, and Elastic Properties. AB - BACKGROUND: The filum terminale is a fibrous band, consisting of the filum terminale internum (FTI), connecting the conus medullaris (CM) with the dural sac (DS), and the filum terminale externum (FTE), connecting the DS with the coccyx. Despite its importance in tethered cord syndrome, published anatomic and physiologic data on the filum terminale remain scarce. We describe 1) the dimensions and position of the FTI and FTE; 2) the histology of the FTI-DS-FTE transition zone; and 3) the extensibility and elastic properties of the FTI and the CM. METHODS: Anatomic measurements were performed on 10 fresh and 10 embalmed human cadavers. Four other fresh cadavers were used for strain and elasticity measurements. RESULTS: The mean FTI and FTE lengths were 158.75 and 69.33 mm, respectively. From cranially to caudally, the FTI diameter decreased from 1.93 to 0.69 mm. The most frequent vertebral level of the CM-FTI and the FTI-DS-FTE junction were L1 and S2, respectively. FTE length correlates with body length (r = 0.54; P = 0.014) and with FTI-DS-FTE junction vertebral level (rho =-0.76; P < 0.001). Histologically, the FTI fuses with DS fibers and continues as FTE. The FTI and the CM show an exponential loaded weight-strain relationship, with the FTI showing higher strain than the CM and almost perfect elastic properties. The CM strain is increased when the dentate ligaments are cut. CONCLUSIONS: The FTI is an overturned oblate cone-shaped structure, showing bigger strain under weight loading compared with the CM, thereby protecting the CM from traction, together with the dentate ligaments. PMID- 26805694 TI - Time to Revive the Value of the Pseudocapsule in Endoscopic Endonasal Transsphenoidal Surgery for Growth Hormone Adenomas. AB - OBJECTIVE: To investigate the role of endoscopic endonasal transsphenoidal surgery and the pseudocapsule in the treatment of growth hormone adenomas. METHODS: The study included 43 patients (age range, 21-64 years) with growth hormone adenomas treated with an endoscopic endonasal approach. We compared the tumor characteristics and surgical outcomes of cases with (group A, 21 cases, from November 2013 to January 2015) and without (group B, 22 cases, from October 2011 to October 2013) extra-pseudocapsule resection. RESULTS: The preoperative demographics, tumor characteristics, and surgical complications were not significantly different between groups A and B. Postoperative remission without adjuvant therapy was achieved in 18 of 21 cases (85.7%) in group A, which was significantly greater than that observed in group B (12 of 22 cases [54.4%]). In group A, the pseudocapsules were verified by endoscopy and histopathology. The pseudocapsule was removed en bloc with the whole adenoma in only 5 cases (23.8%). For the remaining 16 patients (76.2%), following extra-pseudocapsule dissection, incomplete pseudocapsule removals with intracapsule procedures were achieved. CONCLUSIONS: The combination of extra-pseudocapsule resection and endoscopy led to a high rate of gross total tumor resection and endocrinologicl remission in acromegalic patients compared with the group with intracapsular resection. Extra pseudocapsule resection resulted in no additional postoperative complications. PMID- 26805695 TI - Dislocated Pacemaker Electrode Simulating Focal Epileptic State in a Patient with Subdural Hematoma-Case Report and Review of the Literature. AB - BACKGROUND: Due to demographic changes, the number of patients with traumatic brain injury carrying a cardiac resynchronization therapy device is increasing. One of the common complications of subdural hematoma (SDH) is epilepsy, whereas one of the most frequent early complications after cardiac resynchronization therapy device implantation is lead dislocation. The latter might then cause unintended skeletal muscle stimulation that might be misinterpreted in seizure prone patients. CASE DESCRIPTION: An 86-year-old female patient with an initially conservatively treated SDH on the right side presented with a tonic muscle contraction in her left arm 2 weeks after the trauma not responding to antiepileptic therapy. A computed tomography scan revealed residual hematoma on the right side with regular, time-dependent resorption. The muscle contraction was misdiagnosed as a focal epileptic state leading to evacuation of the chronic SDH. Additionally, routine postoperative chest radiographs were performed. Postoperatively, the tonic muscle contraction in her arm persisted. Chest radiographs revealed a dislocation of the left ventricular electrode, which appeared retracted into the left subclavian vein, next to the plexus brachialis. After deactivating the electrode, the alleged focal state ceased. CONCLUSIONS: In case of refractory treatment of epilepsy, dislocation of pacemaker electrodes is a, most certainly, rare but possible differential diagnosis. Confirmation of electrode position and function is easily and quickly feasible and will help prevent futile seizure-directed therapy. PMID- 26805696 TI - The Role of Conservative Management in Incidental Os Odontoideum. AB - BACKGROUND: Os odontoideum is a relatively rare but significant condition of the cervical spine that has potentially life-threatening complications, including vertebral artery dissection, leading to permanent neurologic disability and even death. Unfortunately, the literature is not clear as to the best management approach for os odontoideum. As such, clinicians and their patients are still left with difficult and uncertain treatment decisions in the absence of a clinical consensus. CASE DESCRIPTION: A 20-year-old male was brought in after an assault and found to have os odontoideum on routine investigation. He was informed of management options and elected to undergo a conservative management approach with radiologic surveillance. The patient subsequently became symptomatic and required surgical fixation. CONCLUSIONS: This case illustrates that in the event an asymptomatic case of os odontoideum with radiological instability is managed conservatively, careful clinical and radiologic follow-up is essential as such cases can become symptomatic. PMID- 26805697 TI - Intramedullary Tuberculoma Combined with Abscess: Case Report and Literature Review. AB - BACKGROUND: Intramedullary spinal tuberculoma combined with abscess has low incidence and could easily be misdiagnosed. Given the rarity of spinal intramedullary tuberculoma, there is no standardized treatment protocol for this condition. We reported the case of a 28-year-old male who was diagnosed with intramedullary tuberculoma combined with abscess and treated with antituberculosis therapy followed by surgery. CASE DESCRIPTION: A 28-year-old male was admitted to our hospital with lower back pain and lower limb sensory and motor dysfunction. The radiographic results indicated tuberculosis (TB). The patient was suggested to undergo anti-TB therapy and was later transferred to Tuberculosis Hospital for systemic treatment for 20 days. He was readmitted to our hospital because of aggravating syndromes including impaired superficial sensation below the T11 level, spastic paresis with muscle strength of 0/5 in both lower extremities, and exaggerated bilateral tendon reflexes. To alleviate the neurologic dysfunction, surgery was undertaken. The postoperative diagnosis was thoracic intramedullary TB combined with abscess. He reported marked improvement in lower limb motor and sensory function the day after surgery, and his muscle strength recovered to 3/5. CONCLUSIONS: Although intramedullary TB combined with abscess is clinically rare, it should be taken into consideration when patients present with intramedullary space-occupying lesions with TB lesions elsewhere. Most patients respond well to the anti-TB therapy, but for those with severe spinal cord compression or those irresponsive to the drug therapy, surgical intervention could facilitate neurologic recovery and improve the prognosis. PMID- 26805698 TI - Cerebral Aneurysm Clipping Surgery Simulation Using Patient-Specific 3D Printing and Silicone Casting. AB - BACKGROUND: Neurosurgery simulator development is growing as practitioners recognize the need for improved instructional and rehearsal platforms to improve procedural skills and patient care. In addition, changes in practice patterns have decreased the volume of specific cases, such as aneurysm clippings, which reduces the opportunity for operating room experience. OBJECTIVE: The authors developed a hands-on, dimensionally accurate model for aneurysm clipping using patient-derived anatomic data and three-dimensional (3D) printing. Design of the model focused on reproducibility as well as adaptability to new patient geometry. METHODS: A modular, reproducible, and patient-derived medical simulacrum was developed for medical learners to practice aneurysmal clipping procedures. Various forms of 3D printing were used to develop a geometrically accurate cranium and vascular tree featuring 9 patient-derived aneurysms. 3D printing in conjunction with elastomeric casting was leveraged to achieve a patient-derived brain model with tactile properties not yet available from commercial 3D printing technology. An educational pilot study was performed to gauge simulation efficacy. RESULTS: Through the novel manufacturing process, a patient-derived simulacrum was developed for neurovascular surgical simulation. A follow-up qualitative study suggests potential to enhance current educational programs; assessments support the efficacy of the simulacrum. CONCLUSIONS: The proposed aneurysm clipping simulator has the potential to improve learning experiences in surgical environment. 3D printing and elastomeric casting can produce patient derived models for a dynamic learning environment that add value to surgical training and preparation. PMID- 26805699 TI - Effects of strengthening and stretching exercise programmes on kinematics and kinetics of running in older adults: a randomised controlled trial. AB - The aim of this study was to investigate the effects of strengthening and stretching exercises on running kinematics and kinetics in older runners. One hundred and five runners (55-75 years) were randomly assigned to either a strengthening (n = 36), flexibility (n = 34) or control (n = 35) group. Running kinematics and kinetics were obtained using an eight-camera system and an instrumented treadmill before and after the eight-week exercise protocol. Measures of strength and flexibility were also obtained using a dynamometer and inclinometer/goniometer. A time effect was observed for the excursion angles of the ankle sagittal (P = 0.004, d = 0.17) and thorax/pelvis transverse (P < 0.001, d = 0.20) plane. Similarly, a time effect was observed for knee transverse plane impulse (P = 0.013, d = 0.26) and ground reaction force propulsion (P = 0.042, d = -0.15). A time effect for hip adduction (P = 0.006, d = 0.69), ankle dorsiflexion (P = 0.002, d = 0.47) and hip internal rotation (P = 0.048, d = 0.30) flexibility, and hip extensor (P = 0.001, d = -0.48) and ankle plantar flexor (P = 0.01, d = 0.39) strength were also observed. However, these changes were irrespective of exercise group. The results of the present study indicate that an eight-week stretching or strengthening protocol, compared to controls, was not effective in altering age-related running biomechanics despite changes in ankle and trunk kinematics, knee kinetics and ground reaction forces along with alterations in muscle strength and flexibility were observed over time. PMID- 26805700 TI - MKK3 as oncotarget. PMID- 26805701 TI - [Therapeutic restraint management in Intensive Care Units: Phenomenological approach to nursing reality]. AB - AIMS: To identify nursing experience on physical restraint management in Critical Care Units. To analyse similarities and differences in nursing experience on physical restraint management according to the clinical context that they are involved in. METHOD: A multicentre phenomenological study was carried out including 14 Critical Care Units in Madrid, classified according to physical restraint use: Common/systematic use, lacking/personalised use, and mixed use. Five focus groups (23 participants were selected following purposeful sampling) were convened, concluding in data saturation. Data analysis was focused on thematic content analysis following Colaizzi's method. FINDINGS: Six main themes: Physical restraint meaning in Critical Care Units, safety (self-retreat vital devices), contribution factors, feelings, alternatives, and pending issues. Although some themes are common to the 3 Critical Care Unit types, discourse differences are found as regards to indication, feelings, systematic use of pain and sedation measurement tools. CONCLUSIONS: In order to achieve real physical restraint reduction in Critical Care Units, it is necessary to have a deep understanding of restraints use in the specific clinical context. As self-retreat vital devices emerge as central concept, some interventions proposed in other settings could not be effective, requiring alternatives for critical care patients. Discourse variations laid out in the different Critical Care Unit types could highlight key items that determine the use and different attitudes towards physical restraint. PMID- 26805703 TI - Differences in the intensity of light-induced fluorescence emitted by resin composites. AB - BACKGROUND: The aims of this study were to compare the intensities of fluorescence emitted by different resin composites as detected using quantitative light-induced fluorescence (QLF) technology, and to compare the fluorescence intensity contrast with the color contrast between a restored composite and the adjacent region of the tooth. METHODS: Six brands of light-cured resin composites (shade A2) were investigated. The composites were used to prepare composite discs, and fill holes that had been prepared in extracted human teeth. White light and fluorescence images of all specimens were obtained using a fluorescence camera based on QLF technology (QLF-D) and converted into 8-bit grayscale images. The fluorescence intensity of the discs as well as the fluorescence intensity contrast and the color contrast between the composite restoration and adjacent tooth region were calculated as grayscale levels. RESULTS: The grayscale levels for the composite discs differed significantly with the brand (p<0.001): DenFil (10.84+/-0.35, mean+/-SD), Filtek Z350 (58.28+/-1.37), Premisa (156.94+/-1.58), Grandio (177.20+/-0.81), Charisma (207.05+/-0.77), and Gradia direct posterior (211.52+/-1.66). The difference in grayscale levels between a resin restoration and the adjacent tooth was significantly greater in fluorescence images for each brand than in white-light images, except for the Filtek Z350 (p<0.05). However, the Filtek Z350 restoration was distinguishable from the adjacent tooth in a fluorescence image. CONCLUSIONS: The intensities of fluorescence detected from the resin composites varied. The differences between the composite and adjacent tooth were greater for the fluorescence intensity contrast than for the colors observed in the white-light images. PMID- 26805702 TI - Restoration of Tricuspid Valve Mechanism at the Level of Displaced Septal and Posterior Leaflets in Ebstein's Anomaly. AB - BACKGROUND: Surgical techniques currently used for the repair of Ebstein's anomaly comprise reconstruction of the tricuspid valve mechanism at the level of the true annulus with or without plication of the atrialized right ventricle. However, performing this procedure for patients with a dysmorphic anterior leaflet (i.e., insufficient leaflet tissue and decreased mobility due to tethering) may necessitate technical modifications. METHODS: A retrospective review was performed of 31 patients (seven males and 24 females, median age at operation 31 years) with Ebstein's anomaly, who underwent tricuspid valve repair between March 2002 and December 2014. The original Hetzer technique (annulus to annulus approximation) was employed for six patients with a well-formed anterior leaflet. In 25 patients, the tricuspid valve mechanism was restored at the displaced septal leaflet by approximating the anterior leaflet attachment in the true annulus to the displaced septal leaflet attachment in the mid-septum. A bidirectional superior cavopulmonary anastomosis was added in 27 of 31 (87%) patients. RESULTS: No early or late death occurred during the median follow-up of 66 months (1-138 months). Immediate postoperative tricuspid regurgitation was trivial to mild in 22 patients, and the median preoperative, immediate postoperative, and last follow-up tricuspid regurgitation jet areas in 21 adult patients were 23.3 cm2, 10.4 cm2, and 7.0 cm2, respectively. Two patients underwent reoperation at 81 and 119 months postoperatively. Five-year freedom from severe tricuspid regurgitation or reoperation was 93.2%. CONCLUSION: Restoration of the tricuspid valve mechanism at the level of displaced septal leaflet leads to excellent long-term outcomes. The addition of the bidirectional superior cavopulmonary anastomosis has contributed to the success of this technique. PMID- 26805704 TI - Characteristic Fluctuations in Glycosidically Bound Volatiles during Tea Processing and Identification of Their Unstable Derivatives. AB - A recently developed method enabled us to simultaneously characterize and quantitate glycosidically bound volatiles (GBVs) at picomole levels using liquid chromatography-mass spectrometry (LC-MS). On the basis of the analytical data it is possible to screen tea varieties most suitable for black tea processing, in which higher concentrations of primeverosides accumulate. The primeverosides decreased at the rolling step in black tea processing, whereas the glucopyranosides did not change much. The total contents of GBVs gradually increased at the withering steps and then remarkably increased after the fixing step at 230 degrees C, during oolong tea processing. The presence of 6'-O malonyl ester type beta-D-glucopyranosides in the tea samples suggested a contribution to the increment in glucopyranosides during oolong tea processing. The method was also used to analyze GBVs and their derivatives to understand their possible role in the metabolic pathway of tea. PMID- 26805705 TI - Histologic and immunohistochemical predictors of clinical behavior for feline diffuse iris melanoma. AB - OBJECTIVE: To determine histologic and immunohistochemical predictors of metastasis of feline diffuse iris melanoma (FDIM). ANIMALS: Globes from 47 client owned cats enucleated for FDIM between January 1985 and December 2013. PROCEDURES: Hematoxylin and eosin-stained sections were evaluated for neoplastic invasiveness and cell morphology, necrosis within the neoplasm, inflammation, and glaucoma. Sections were immunolabeled with antibodies against melan-A, PNL2, E cadherin, or B-Raf, and label intensity, percentage of labeled cells, and label homogeneity were semi-quantitatively graded. Medical records were evaluated, and referring veterinarians and clients were contacted to determine whether cats developed metastasis following enucleation. The log-rank test or Cox proportional hazards model was used to determine associations between histologic or immunohistochemical parameters and metastasis. RESULTS: Metastasis was suspected or confirmed in 9/47 (19%) cats. Extrascleral extension, necrosis within the neoplasm, a mitotic index of >7 mitoses in 10 high-power (*400) fields, choroidal invasion, and increased E-cadherin and melan-A label intensity were each associated with increased rate of metastasis. PNL2 label homogeneity was associated with decreased rate of metastasis. Decreased PNL2 label intensity and an increasing percentage of neoplastic cells labeled for melan-A each approached significance for increased rate of metastasis. CONCLUSIONS: We report four histologic and three immunohistochemical parameters helpful in determining cats at risk of metastasis of FDIM. Further studies should determine if B-Raf mutations identified in human malignant melanomas are found in cats with FDIM and assess benefits of adjunctive therapy following enucleation of eyes with FDIM bearing poor prognostic indicators. PMID- 26805706 TI - Onset of particle trapping and release via acoustic bubbles. AB - Trapping and sorting of micro-sized objects is one important application of lab on a chip devices, with the use of acoustic bubbles emerging as an effective, non contact method. Acoustically actuated bubbles are known to exert a secondary radiation force (FSR) on micro-particles and stabilize them on the bubble surface, when this radiation force exceeds the external hydrodynamic forces that act to keep the particles in motion. While the theoretical expression of FSR has been derived by Nyborg decades ago, no direct experimental validation of this force has been performed, and the relationship between FSR and the bubble's ability to trap particles in a given lab on a chip device remains largely empirical. In order to quantify the connection between the bubble oscillation and the resultant FSR, we experimentally measure the amplitude of bubble oscillations that give rise to FSR and observe the trapping and release of a single microsphere in the presence of the mean flow at the corresponding acoustic parameters using an acoustofluidic device. By combining well-developed theories that connect bubble oscillations to the acoustic actuation, we derive the expression for the critical input voltage that leads to particle release into the flow, in good agreement with the experiments. PMID- 26805707 TI - The direct observation of charge separation dynamics in CdSe quantum dots/cobaloxime hybrids. AB - In this work, we investigated photoinduced charge separation dynamics in a CdSe quantum dot/cobaloxime molecular catalyst hybrid using the combination of transient optical (OTA) and X-ray absorption (XTA) spectroscopy. We show that ultrafast charge separation occurs through electron transfer (ET) from CdSe QDs to cobaloxime. In addition to the enhanced 1S exciton bleach recovery in CdSe QDs due to the presence of cobaloxime, the direct evidence for ET process, i.e. the formation of the transient charge separated state, is captured by XTA. These results not only demonstrate the capability of XTA to capture the transient species during the photoinduced reactions in hybrid nanostructures but also enhance our understanding of charge separation dynamics in semiconductor nanocrystal/molecular catalyst hybrid. PMID- 26805708 TI - Absolute standardization of the impurity (121)Te associated to the production of the radiopharmaceutical (123)I. AB - (123)I is widely used for radiodiagnostic procedures. It is produced by reaction of (124)Xe (p,2n) (123)Cs ->(123)Xe ->(123)I in cyclotrons. (121)Te and (125)I appear in a photon energy spectrum as impurities. An activity of (121)Te was calibrated absolutely by sum-peak method and its photon emitting probability was estimated, whose results were consistent with published results. PMID- 26805709 TI - Mechanochromism and Mechanical-Force-Triggered Cross-Linking from a Single Reactive Moiety Incorporated into Polymer Chains. AB - Incorporation of small reactive moieties, the reactivity of which depends on externally imposed load (so-called mechanophores) into polymer chains offers access to a broad range of stress-responsive materials. Here, we report that polymers incorporating spirothiopyran (STP) manifest both green mechanochromism and load-induced addition reactions in solution and solid. Stretching a macromolecule containing colorless STP converts it into green thiomerocyanine (TMC), the mechanically activated thiolate moiety of which undergoes rapid thiol ene click reactions with certain reactive C=C bonds to form a graft or a cross link. The unique dual mechanochemical response of STP makes it of potentially great utility both for the design of new stress-responsive materials and for fundamental studies in polymer physics, for example, the dynamics of physical and mechanochemical remodeling of loaded materials. PMID- 26805711 TI - Ag nanoparticles generated using bio-reduction and -coating cause microbial killing without cell lysis. AB - Cost-effective "green" methods of producing Ag nanoparticles (NPs) are being examined because of the potential of these NPs as antimicrobials. Ag NPs were generated from Ag ions using extracellular metabolites from a soil-borne Pythium species. The NPs were variable in size, but had one dimension less than 50 nm and were biocoated; aggregation and coating changed with acetone precipitation. They had dose-dependent lethal effects on a soil pseudomonad, Pseudomonas chlororaphis O6, and were about 30-fold more effective than Ag(+) ions. A role of reactive oxygen species in cell death was demonstrated by use of fluorescent dyes responsive to superoxide anion and peroxide accumulation. Also mutants of the pseudomonad, defective in enzymes that protect against oxidative stress, were more sensitive than the wild type strain; mutant sensitivity differed between exposure to Ag NPs and Ag(+) ions demonstrating a nano-effect. Imaging of bacterial cells treated with the biocoated Ag NPs revealed no cell lysis, but there were changes in surface properties and cell height. These findings support that biocoating the NPs results in limited Ag release and yet they retained potent antimicrobial activity. PMID- 26805712 TI - Broadband non-reciprocal transmission of sound with invariant frequency. AB - We design and experimentally demonstrate a broadband yet compact acoustic diode (AD) by using an acoustic nonlinear material and a pair of gain and lossy materials. Due to the capabilities of maintaining the original frequency and high forward transmission while blocking backscattered wave, our design is closer to the desired features of a perfect AD and is promising to play the essential diode like role in realistic acoustic systems, such as ultrasound imaging, noise control and nondestructive testing. Furthermore, our design enables improving the sensitivity and the robustness of device simultaneously by tailoring an individual structural parameter. We envision our design will take a significant step towards the realization of applicable acoustic one-way devices, and inspire the research of non-reciprocal wave manipulation in other fields. PMID- 26805714 TI - Barbed versus traditional sutures for wound closure in knee arthroplasty: a systematic review and meta-analysis. AB - Sutures are an increasing focus of research in knee arthroplasty (KA). Whether knotless barbed sutures (KBS) are safe and efficient in KA remains controversial. The objective of our study is to compare the clinical outcomes of KA according to wound closure method: KBS versus knotted traditional sutures (KTS). To clarify this, we conducted a systematic review and meta-analysis. Nine articles involving 10 studies were included in this study. The dataset consisted of 1729 patients with 1754 KA. Among these, 814 patients' wounds were closed with KBS and 915 with KTS. Our analysis indicates that KBS is preferable for KA wound closure given its shorter wound closure time and lower total cost; postoperative Knee Society scores and complication rates were similar to those of surgeries using KTS. The subgroup analysis revealed that closure of arthrotomy with KBS appears to be associated with a lower risk of complications. This meta-analysis indicates that use of KBS in KA reduces operative time and cost. KBS is the preferred option for wound closures, including arthrotomy and reattachment of subcutaneous and subcuticular tissues. Given the possible biases, adequately powered and better designed studies with longer follow-up are required to reach a firmer conclusion. PMID- 26805715 TI - Update on molecular mechanisms of corticosteroid resistance in chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is an inflammatory and irreversible pulmonary disorder that is characterized by inflammation and airway destruction. In recent years, COPD has become a global epidemic due to increased air pollution and exposure to cigarette smoke. Current therapeutics using bronchiodialator and anti-inflammatory corticosteroids are most widely used for all patients with persistent COPD, but these approaches are disappointing due to limited improvement in symptom control and survival rate. More importantly, a certain number of COPD patients are resistant to the corticosteroid treatment and their symptoms worsen. Therefore, more effective anti-inflammatory drugs and combinational treatment are required. Understanding of the underlying molecular and immunological mechanisms is critical to developing new therapeutics. Lung inflammation and the released pro-inflammatory cytokines affect glucocorticoid receptor (GR), histone deacetylase 2 (HDAC2) and surfactant protein D (SP-D) activities in many cell types. Macrophages, neutrophils, airway epithelial cells and lymphocytes are involved in the induction of corticosteroid resistance. This review updated the recent advances in molecular and immunological mechanisms of steroid resistance among patients and animal models with COPD. Meanwhile we discussed novel therapeutic approaches in controlling lung inflammation and improving corticosteroid sensitivity among the steroid resistant patients with COPD. PMID- 26805717 TI - The influence of crossbreeding on collagen solubility and tenderness of Infraspinatus and Semimembranosus muscles of semi-intensively reared young bulls. AB - The aim of the present study was to investigate the effects of crossbreeding on collagen content and solubility, shear force (WBSF) and the eating quality of Infraspinatus (INF) and Semimembranosus (SM) muscles of young bulls and the relationships between collagen content and solubility, shear force and the eating quality of beef. The experimental material comprised muscles of crossbred young bulls (about 600 days old) of Polish Holstein-Friesian (PHF) * Limousine (LM) (n = 10), PHF * Charolaise (CH) (n = 9), PHF * Hereford (HER) (n = 9) breeds. The crossbreeding influenced WBSF, aroma and taste, total, water-soluble, acid soluble, total soluble and insoluble collagen content, as well as the acid soluble, total soluble and insoluble collagen proportions. WBSF was significantly negatively correlated with sensorial tenderness and water-soluble collagen content. The eating quality of beef obtained from different crossbreds was similar; however, the meat from PHF * LM and PHF * HER bulls had lower WBSF values than PHF * CH bulls. (c) 2016 Japanese Society of Animal Science. PMID- 26805720 TI - Behavioural recovery after treatment for varicose veins. AB - BACKGROUND: The aim of this study was to assess behavioural recovery from the patient's perspective as a prespecified secondary outcome in a multicentre parallel-group randomized clinical trial comparing ultrasound-guided foam sclerotherapy (UGFS), endovenous laser ablation (EVLA) and surgery for the treatment of primary varicose veins. METHODS: Participants were recruited from 11 UK sites as part of the CLASS trial, a randomized trial of UGFS, EVLA or surgery for varicose veins. Patients were followed up 6 weeks after treatment and asked to complete the Behavioural Recovery After treatment for Varicose Veins (BRAVVO) questionnaire. This is a 15-item instrument that covers eight activity behaviours (tasks or actions an individual is capable of doing in an idealized situation) and seven participation behaviours (what the individual does in an everyday, real world situation) that were identified to be important from the patient's perspective. RESULTS: A total of 798 participants were recruited. Both UGFS and EVLA resulted in a significantly quicker recovery compared with surgery for 13 of the 15 behaviours assessed. UGFS was superior to EVLA in terms of return to full time work (hazard ratio 1.43, 95 per cent c.i. 1.11 to 1.85), looking after children (1.45, 1.04 to 2.02) and walks of short (1.48, 1.19 to 1.84) and longer (1.32, 1.05 to 1.66) duration. CONCLUSION: Both UGFS and EVLA resulted in more rapid recovery than surgery, and UGFS was superior to EVLA for one-quarter of the behaviours assessed. The BRAVVO questionnaire has the potential to provide important meaningful information to patients about their early recovery and what they may expect to be able to achieve after treatment. PMID- 26805721 TI - Reticular erythematous mucinosis on a mastectomy scar and relapse after mammary reconstruction. PMID- 26805722 TI - Mechanisms of vertebrate embryo segmentation: Common themes in trunk and limb development. AB - Various ultradian rhythms ensure proper temporal regulations during embryo development. The embryo molecular clock, which was first identified in the presomitic mesoderm (PSM) underlying periodic somite formation, is one among them. Somites are the earliest manifestation of the segmented vertebrate body and they are formed with strict temporal precision. The tetrapod limb is also a segmented structure and the formation of limb bone elements have also been associated with a molecular clock, operating in the distal limb mesenchyme. In both the PSM and the distal limb mesenchyme, the molecular clock (MC) is influenced by FGF, SHH and RA, which are also the key regulators of the development of these tissues. While somitogenesis has been continuously scrutinized to understand the mechanisms of the MC, the limb bud has served as an outstanding paradigm to study how a cohort of undifferentiated cells is organized into functional 3D structures. The fact that both the trunk and limb development are shaped by the MC and by common signaling molecules has prompted the exciting possibility of establishing parallelisms between somitogenesis and limb development. Systematically correlating various parameters during trunk and limb development will help us to appreciate the common principles underlying segmented structure formation and allow the rise of new questions in order to fill the gaps in our present understanding. In this review we have established the parallelisms between somitogenesis and limb development at the level of gene expression patterns and their regulation. Finally, we have also discussed the most evident new avenues this exercise could open to the scientific community. PMID- 26805724 TI - Thirst responses following high intensity intermittent exercise when access to ad libitum water intake was permitted, not permitted or delayed. AB - An increase in subjective feelings of thirst and ad libitum drinking caused by an increase in serum osmolality have been observed following high intensity intermittent exercise (HIIE) compared to continuous exercise. The increase in serum osmolality is closely linked to the rise in blood lactate and serum sodium concentrations. However, during an ensuing recovery period after HIIE when serum osmolality will decrease, the resultant effect on sensations of thirst and subsequent water intake is unclear. Therefore the aim of the study was to assess the sensations of thirst and subsequent effect on ad libitum water consumption when water intake was immediately allowed, delayed or prevented following a period of HIIE. METHODS: Twelve males (26+/-4 years, 80.1+/-9.3 kg, 1.81+/-0.05 m, VO2peak 60.1+/-8.9 ml.kg(-1).min(-1)) participated in three randomised trials undertaken 7-14 days apart. Participants rested for 30 min then completed a 60 min HIIE exercise period (20*1 min at 100% VO2peak with 2 min rest) followed by 60 min of recovery, during which ad libitum water intake was provided immediately (W), delayed until the final 30 min (W30) or not permitted (NW). Body mass was measured at the start and end of the trial. Blood lactate and serum sodium concentrations serum osmolality and sensation of thirst were measured at baseline, immediately post-exercise and during the recovery. RESULTS: Body mass loss was different between all trials (W: 0.25+/-0.45, W30: 0.49+/-0.37, NW: 1.29+/-0.37%; p<0.05). Sensations of thirst peaked post-exercise and decreased in W and W30 following water ingestion (p<0.05). Total voluntary water intake was greater in W trial (0.846+/-0.417 vs. 0.630+/-0.277l; p<0.05) but was similar during the first 30 min period of allowed drinking (0.618+/-0.297 vs. 0.630+/ 0.277l; p>0.05). Serum osmolality (299+/-6 vs. 298+/-5 vs. 298+/-3 mOsmol.kg( 1)), blood lactate (7.1+/-1.1 vs. 7.2+/-1.1 vs. 7.1+/-1.2 mmol.l(-1)) and serum sodium concentrations (142+/-2 vs. 145+/-2 vs. 145+/-2 mmol.l(-1)) peaked post exercise (W vs. W30 vs. NW; p<0.05) but were not different between trials (p>0.05). CONCLUSIONS: Sensations of thirst were increased following HIIE and remained until satiated by water intake. This was despite the likely primary stimulus, serum osmolality, decreasing during the recovery period following a post-exercise peak. A combined effect of reduction in blood lactate and serum sodium concentrations, restoration of plasma volume and water intake contributed to the similar decrease in serum osmolality observed throughout the trials. PMID- 26805723 TI - The Amino Acid Transporter JhI-21 Coevolves with Glutamate Receptors, Impacts NMJ Physiology, and Influences Locomotor Activity in Drosophila Larvae. AB - Changes in synaptic physiology underlie neuronal network plasticity and behavioral phenomena, which are adjusted during development. The Drosophila larval glutamatergic neuromuscular junction (NMJ) represents a powerful synaptic model to investigate factors impacting these processes. Amino acids such as glutamate have been shown to regulate Drosophila NMJ physiology by modulating the clustering of postsynaptic glutamate receptors and thereby regulating the strength of signal transmission from the motor neuron to the muscle cell. To identify amino acid transporters impacting glutmatergic signal transmission, we used Evolutionary Rate Covariation (ERC), a recently developed bioinformatic tool. Our screen identified ten proteins co-evolving with NMJ glutamate receptors. We selected one candidate transporter, the SLC7 (Solute Carrier) transporter family member JhI-21 (Juvenile hormone Inducible-21), which is expressed in Drosophila larval motor neurons. We show that JhI-21 suppresses postsynaptic muscle glutamate receptor abundance, and that JhI-21 expression in motor neurons regulates larval crawling behavior in a developmental stage specific manner. PMID- 26805725 TI - Understanding the role of personality and alexithymia in food preferences and PROP taste perception. AB - Taste perception and food preferences are influenced by a variety of factors, including personality characteristics. The aims of this study were to examine the role of personality characteristics, such as alexithymia (a personality construct characterized by inability to identify, describe, and work with one's own feelings), in: 1) taste responses to the bitter genetic taste-marker PROP and 2) food liking. We studied 649 healthy subjects residing in six genetically-isolated villages of Northeast Italy. Data on PROP taste responsiveness, food liking, personality characteristics and TAS2R28 genotypes were collected. Results showed that PROP non-tasters had higher alexithymia scores than PROP tasters. Moreover, the presence of alexithymia in heterozygous individuals for the rs1726886 polymorphism of the TAS2R38 gene was associated with a reduction in the perceived intensity of PROP. Finally, higher alexithymia scores were associated with liking of alcohol, sweets and fats/meats whereas lower alexithymia scores were related to liking of vegetables, condiments and strong cheeses, Measures of temperament, character, anxiety and depression were also related to food liking. Our findings suggest that: 1) alexithymia, in addition to the TAS2R38 polymorphism, may play a role in responsiveness to the aversive and bitter taste of PROP; and 2) alexithymia, in combination with other personality traits, may provide important insights for better understanding food liking. PMID- 26805726 TI - An Efficient Amide-Aldehyde-Alkene Condensation: Synthesis for the N-Allyl Amides. AB - The allylamine skeleton represents a significant class of biologically active nitrogen compounds that are found in various natural products and drugs with well recognized pharmacological properties. In this personal account, we will briefly discuss the synthesis of allylamine skeletons. We will focus on showing a general protocol for Lewis acid-catalyzed N-allylation of electron-poor N-heterocyclic amides and sulfonamide via an amide-aldehyde-alkene condensation reaction. The substrate scope with respect to N-heterocyclic amides, aldehydes, and alkenes will be discussed. This method is also capable of preparing the Naftifine motif from N-methyl-1-naphthamide or methyl (naphthalene-1-ylmethyl)carbamate, with paraformaldehyde and styrene in a one-pot manner. PMID- 26805727 TI - Ligand-based virtual screening and inductive learning for identification of SIRT1 inhibitors in natural products. AB - Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase, and its dysregulation can lead to ageing, diabetes, and cancer. From 346 experimentally confirmed SIRT1 inhibitors, an inhibitor structure pattern was generated by inductive logic programming (ILP) with DMax Chemistry Assistant software. The pattern contained amide, amine, and hetero-aromatic five-membered rings, each of which had a hetero-atom and an unsubstituted atom at a distance of 2. According to this pattern, a ligand-based virtual screening of 1 444 880 active compounds from Chinese herbs identified 12 compounds as inhibitors of SIRT1. Three compounds (ZINC08790006, ZINC08792229, and ZINC08792355) had high affinity (-7.3, -7.8, and -8.6 kcal/mol, respectively) for SIRT1 as estimated by molecular docking software AutoDock Vina. This study demonstrated a use of ILP and background knowledge in machine learning to facilitate virtual screening. PMID- 26805728 TI - Obstetrician-Gynecologist Practices and Beliefs Regarding External Genitalia Inspection and Speculum Examinations in Healthy Older Asymptomatic Women. AB - OBJECTIVES: To understand obstetrician-gynecologist perceptions of the value of external genitalia inspection and speculum examinations in older and younger healthy women across the life span. DESIGN: National survey from May 2010 to January 2011 asking obstetrician-gynecologists about the need for and importance of external inspection and speculum examination in four scenarios of asymptomatic healthy women aged 70, 55, 35, and 18 who present for routine health visits. Separate questions asked about the importance of various reasons for these examinations. SETTING: Mail-in survey of a national sample of obstetrician gynecologists. PARTICIPANTS: Probability sample of obstetrician-gynecologists from the American Medical Association Physician Masterfile (N = 521). MEASUREMENTS: Proportion of obstetrician-gynecologists who would perform external inspection and speculum examinations and consider these examinations to be very important. RESULTS: The response rate was 62%. In a healthy 70-year-old woman, 98% of respondents would perform external inspection, and 86% would perform a speculum examination. Ninety percent would perform a speculum examination in a healthy 55-year-old woman after removal of her uterus, cervix, and ovaries. Respondents more often indicated that the external examination was very important in the 70-year-old (63%) than in younger women (46-53%). Reasons rated as very important included identifying cancers and benign lesions, reassuring women of their health, and adhering to standard of care. CONCLUSION: Obstetrician gynecologists would commonly perform external and speculum examinations in asymptomatic women and believe the external examination to be particularly important in older women for cancer detection. Clinicians should discuss limitations of screening pelvic examination guidelines and elicit health goals from older women to provide more person-centered gynecological care. PMID- 26805729 TI - Living Kidney Donor Profile Index: Utility and Limitations. PMID- 26805730 TI - Oxidative and Non-Oxidative Metabolomics of Ethanol. AB - BACKGROUND: It is well known that ethanol can cause significant morbidity and mortality, and much of the related toxic effects can be explained by its metabolic profile. OBJECTIVE: This work performs a complete review of the metabolism of ethanol focusing on both major and minor metabolites. METHOD: An exhaustive literature search was carried out using textual and structural queries for ethanol and related known metabolizing enzymes and metabolites. RESULTS: The main pathway of metabolism is catalyzed by cytosolic alcohol dehydrogenase, which exhibits multiple isoenzymes and genetic polymorphisms with clinical and forensic implications. Another two oxidative routes, the highly inducible CYP2E1 system and peroxisomal catalase may acquire relevance under specific circumstances. In addition to oxidative metabolism, ethanol also originates minor metabolites such as ethyl glucuronide, ethyl sulfate, ethyl phosphate, ethyl nitrite, phosphatidylethanol and fatty acid ethyl esters. These metabolites represent alternative biomarkers since they can be detected several hours or days after ethanol exposure. CONCLUSION: It is expected that knowing the metabolomics of ethanol may provide additional insights to better understand the toxicological effects and the variability of dose response. PMID- 26805731 TI - Modify on the fly: triple quad to high resolution in support of a dermal clinical study requiring an ultra low LLOQ. AB - BACKGROUND: FTIH studies can be challenging due to the varying dosing regimens and rapid data delivery. Chemists are asked to provide ultra-low limits of quantitation to provide an understanding of patient efficacy and safety in order to progress drug development. In a recent dermal study it became necessary to reduce the LLOQ of a small molecule drug from 50 to 1 pg/ml due to reductions in the dose and surface area of drug application. METHODOLOGY: The 50-fold increase in assay sensitivity necessitated the use of a high-resolution mass spectrometer (LC-HRMS) to separate matrix interferences observed when using a unit resolution triple quadrupole MS. CONCLUSION: A sensitive, robust assay was validated to support of a FTIH study using a LC-HRMS. PMID- 26805733 TI - [Effect and Mechanism of Radiosensitization of Poly (ADP-Ribose) Polymerase Inhibitor n Lewis Cells and Xenografts]. AB - BACKGROUND AND OBJECTIVE: The DNA damage of the irradiated tumor cells is mainly single strand breaks (SSBs) and double strand breaks (DSBs), in which the frequency of occurrence of SSBs is dozens of times than DSBs. However, most of the SSBs could be repaired by the Poly (ADP-Ribose) Polymerase (PARP) and other related factors. Recently listed drug-Olaparib (PARP1/PARP2/PARP3 inhibitor) could target the repair pathways of single strand breaks, and recent clinical trials of PARP inhibitors combined with chemotherapy obtained encouraging results. The aim of this study is to investigate the effect and potential mechanism of radiosensitization of Poly (ADP-Ribose) polymerase inhibitor Olaparib on lewis cells and xenografts. METHODS: The inhibition concentration 10% inhibitory concentration (IC10) of Olaparib to Lewis cells was detected by methyl thiazolyltetrazolium (MTT) assay. The radiosensitization effect of Olaparib on Lewis cells was determined by classical colony forming assay. Lewis xenografts models were established, and the mice were randomly divided into four groups: Control group, Olaparib group, Radiotherapy group (RT, 2 Gy * 5 d), Olaparib combined with RT group. Xenograft volume was measured during the treatment. Flow cytometry was used to analyze the apoptosis rate of the Lewis cells in each group, and the apoptosis of xenograft tissues was observed by TUNEL stain. The ralative protein levels of gammaH2AX (associated with DNA strand breaks repair), Bax/Bcl-2, Caspase-3 (apoptosis-associated protein) were detected by Western blot in vitro and in vivo. RESULTS: The IC10 value of Olaparib was 4.4 MUmol/L. The radio-sensitivity enhancement ratio (SER) of Olaparib combined with RT was 1.211 in vitro. Compared with RT (2 Gy * 5 d) alone, the combination of Olaparib with fractionated radiotherapy significantly increased the growth delay of Lewis xenografts (P<0.001). Flow cytometry and TUNEL analysis indicated that the apoptosis rate in the combination group was significantly higher than in RT group in vitro and in vivo (P<0.05). Furthermore, Western blot results confirmed that in the combination group the expression levels of gammaH2AX, Bax, Caspase-3 were increased, while that of Bcl-2 was decreased as opposed to RT group (P<0.05). CONCLUSION: The combination of Olaprib and fractionated radiotherapy can markedly improve the radiobiological effects on lewis cells and xenografts, which may be induced by promoting the formation of DNA double strand break and upregulating the expression of Bax/Bcl-2 pro-apoptotic proteins. PMID- 26805732 TI - [China Experts Consensus on the Diagnosis and Treatment of Advanced Stage Primary Lung Cancer (2016 Version)]. PMID- 26805734 TI - [Mechanism of TRIM24 to Regulate Resistance of Gefitinib in NSCLC cells]. AB - BACKGROUND AND OBJECTIVE: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance significantly limits its use in clinical practice. Study found that TRIM24 was overexpressed in non-small cell lung cancer (NSCLC) tissues and regulate cell growth, cell cycle and apoptosis in lung cell lines. The aim of this study is to explore the mechanism of TRIM24 to regulate resistance of Gefitinib in NSCLC cells. METHODS: MTT and apoptosis were used to detect the change of cell grow and cell apoptosis with down-expression TRIM24 and ShTRIM24 with presence of Gefitinib. Meanwhile, Western blot was used to detect the expression of protein related to apoptosis and AKT signal path. RESULTS: TRIM24 interference could improve the effect of gefitinib on cell growth inhibition and upregulate the cell apoptosis in A549 cell. Down-regulated of endogenous TRIM24 and ShTRIM24 with Gifitinib could also reduce the protein related apoptosis, such as p-BAD and Bcl-2, and the protein PIK3CA related AKT signal path in A549 cell. CONCLUSIONS: TRIM24 could regulate required resistance to Gefitinib via Akt pathway in NSCLC. PMID- 26805735 TI - [Association of Inorganics Accumulation with the Activation of NF-kappaB Signaling Pathway and the iNOS Expression of Lung Tissue in Xuanwei Lung Cancer Patients]. AB - BACKGROUND AND OBJECTIVE: Indoor air pollution induces asthma, leads to chronic obstructive pulmonary disease, and may promote lung cancer. Our previous studies found that the accumulation of inorganic particulate matter that is due to indoor air pollution can lead to damage to alveolar cells and activation of signaling pathway, and ultimately provoke tumorigenesis. The aim of this study is to explore the accumulation of inorganics and activation of nuclear factor kappaB (NF-kappaB)-inducible nitric oxide synthase (iNOS) signaling pathway of lung tissue in Xuanwei lung cancer patients. METHODS: From December 2013 to November 2014, 48 cases Xuanwei patients with lung cancer who underwent surgical treatment from the Third Affiliated Hospital of Kunming Medical University were enrolled in this study and compared with lung cancer patients from other regions. The ultrastructure of postoperative specimens was observed by transmission electron microscopy (TEM) to explore the occurrence of inorganic particles. Serum cytokines were analyzed. Then, the expression levels of NF-kappaB-p65 protein and iNOS protein in postoperative specimens was explored by immunohistochemistry and Western blot. Finally, 8-OHdG accumulation in lung cancer tissues and urine was measured. RESULTS: A large number of nanoscale inorganics were observed in alveolar type II cells and macrophages located in adjacent tissues of lung cancer with Xuanwei patients. Silicon (Si) content was found in inorganic elemental analysis. The serum interleukin (IL)-1beta levels (31.50 +/- 19.16) pg/mL of Xuanwei lung-cancer patients were remarkably higher than those from other regions (11.33 +/- 6.94) pg/mL (P<0.01), with statistically significant difference. The pathological tissues of Xuanwei lung-cancer patients express NF-kappaB-p65, and iNOS expression were significantly higher than those of patients from non-Xuanwei regions. No significant difference was found between cancerous and normal adjacent tissues. Xuanwei lung-cancer tissues and urine 8-OHdG level (40.124 +/- 8.597) ng/mgCr were significantly higher than those of patients from other regions (25.673 +/- 7.986) ng/mg Cr (P<0.05), with statistically significant difference. CONCLUSIONS: The accumulation of inorganics and the activation of NF kappaB-iNOS signaling pathway may contribute to Xuanwei lung cancer.?. PMID- 26805736 TI - [Value of Immunohistochemical Methods in Detecting EML4-ALK Fusion Mutations: A Meta-analysis]. AB - BACKGROUND AND OBJECTIVE: The fusion between echinoderm microtubule-associated protein 4 (EML4) and anaplastic lymphatic tumor kinase (ALK) rearrangement is present in approximately 5% of non-small cell lung cancer (NSCLC) patients. It has been regarded as another new target gene after epidermal growth factor receptor (EGFR) and K-ras. Figures showed that the disease control rate could reach up to 80% in NSCLC patients with EML4-ALK fusion gene after treated with ALK inhibitors. Thus, exploring an accurate and rapid detecting method is the key in screening NSCLC patients with EML4-ALK expressions. The aim of this study is to analyze the specificity and sensitivity of IHC in detecting EML4-ALK fusion mutations. To evaluate the accuracy and clinical value of this method, and then provide basis for individual molecular therapy of NSCLC patients. METHODS: Using Pubmed database to search all documents required. The deadline of retrieval was February 25, 2015. Then further screening the articles according to the inclusion and exclusion criteria. Using diagnostic test meta-analysis methods to analyze the sensitivity and specificity of the immunohistochemistry (IHC) method compared with fluorescence in situ hybridization (FISH) method. RESULTS: Eleven literatures were added into the meta analysis, there were 3,234 of total cases. The diagnostic odds ratio (DOR) was 1,135.00 (95%CI: 337.10-3,821.46); the area under curve (AUC) of summary receiver operating characteristic curve (SROC) curve was 0.992,3 (SEAUC=0.003,2), the Q* was 0.964,4 (SEQ*=0.008,7). CONCLUSIONS: Immunohistochemical detection of EML4-ALK fusion gene mutation with specific antibody is feasible. It has high sensitivity and specificity. IHC can be a simple and rapid way in screening EML4-ALK fusion gene mutation and exhibits important clinical values. PMID- 26805737 TI - [Role of Interleukin 17 in Lung Carcinogenesis and Lung Cancer Progression]. AB - Interleukin 17 (IL-17) is an important pro-inflammatory cytokine. It plays a critical role in mediating pathogen defense reactions, and the pathological inflammation of autoimmune diseases. IL-17 is also involved in various inflammation-related carcinogenesis. Cigarette smoking is one of the most important risk factors of lung cancer. Chronic inflammation caused by smoking and other factors is accompanied with overexpression of IL-17 within the airway, which reveals a potential relationship between IL-17 and lung carcinogenesis. Furthermore, IL-17 also plays a role in lung cancer progression via different mechanisms. In this paper, we summarized the results of current studies on IL-17 and lung carcinogenesis, as well as lung cancer progression. PMID- 26805740 TI - Oral Squamomelanocytic Tumour in a Dog: a Unique Biphasic Cancer. AB - In human medicine, squamomelanocytic tumour is a malignant cutaneous neoplasm composed of closely intermingled neoplastic squamous cells and melanocytes. A multinodular gingival tumour in a 16-year-old, mixed breed neutered female dog was examined microscopically. Two populations of neoplastic cells, melanocytic and squamous epithelial cells were intermingled. The melanocytic cells were melan A positive and cytokeratin AE1-AE3 negative and the squamous component was cytokeratin AE1-AE3 positive and melan-A negative. Bovine papillomavirus was not identified by immunohistochemistry or polymerase chain reaction. A diagnosis of squamomelanocytic tumour was made. PMID- 26805738 TI - [Response of Erlotinib in Lung Adenocarcinoma Harboring EGFR Sensitive Mutation in Cerebrospinal Fluid: Case Report]. AB - BACKGROUND AND OBJECTIVE: One of the most often distance metastasis site of non small cell lung cancer (NSCLC) is brain and the standard treatment of brain metastasis was radiotheraphy including whole brain irradiation (WBI) and stereotactic radiotherapy (SRT). It has been reported that epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) had the active response in brain metastasis of lung cancer. In the present study, we reported one case of EGFR 19el in cerebrospinal fluid tested by ARMS got partial response given erlotinib. METHODS: Cerebrospinal fluid was collected through lumbar puncture, then cast-off cells and EGFR mutation was analysed. Erlotinib was given with dose of 150 mg, qd. Objective response was evaluated by Response Evaluation Criteriation in Solid Tumours (RECIST) v1.1 and adeverse events were evaluated according to Common Terminology Criteria for Adverse Events v4.0 (CTC AE v4.0). RESULTS: Heterocyst cells were found in cerebrospinal fluid and EGFR mutation was tested as 19del. The patient achieved partial response (PR) of brain metastasis and the effective response in lung was stable disease (SD) after 4 weeks of erlotinib. The progression-free survival (PFS) and overall survival (OS) of brain metastasis was 10.5 months and 11 months respectively. The main adverse event was rash (Grade I). CONCLUSIONS: It was feasible to test EGFR mutation in cerebrospinal fluid and the combination of erlotinib with chemotheraphy would be an appropriate choice to those lung cancer patients who had brain metastasis harboring EGFR sensitive mutation. PMID- 26805741 TI - Immunohistochemical detection of the delayed formation of nonfibrillar large amyloid-beta aggregates. AB - The occurrence of senile plaques consisting of amyloid-beta protein (Abeta) is a major neuropathological hallmark of Alzheimer's disease (AD). We previously developed and characterized monoclonal antibodies 31-2 and 75-2 that specifically bind to nonfibrillar Abeta1-42 aggregates with diameters of more than 220 and 50 nm, respectively. Here, we report the use of these antibodies to examine the aggregation of exogenous Abeta1-42 in cultured rat hippocampal neurons. From 6 to 24 h after transfection of Abeta1-42, antibody 75-2 immunolabeled almost all transfected neurons, whereas 31-2-positive cells were restricted to a part of the transfected neurons and gradually increased in number. Expression of the F19S/L34P-mutant Abeta1-42, which showed less of a tendency to aggregate, resulted in clearly reduced immunoreactivity to both antibodies. We also immunohistochemically investigated the temporal cortices of patients with AD and found that 31-2 preferentially labeled the cores of a subpopulation of large amyloid plaques. The relative number of 31-2-immunoreactive plaques was found to correlate with the Braak stages of neurofibrillary tangles, but not with that of amyloid plaques. These results suggest that 31-2-reactive Abeta aggregates develop with a delayed time course in cultured neurons and amyloid plaques of AD brains. PMID- 26805742 TI - Ozone stomatal flux and O3 concentration-based metrics for Astronium graveolens Jacq., a Brazilian native forest tree species. AB - The current levels of surface ozone (O3) are high enough to negatively affect trees in large regions of Sao Paulo State, southeastern Brazil, where standards for the protection of vegetation against the adverse effects of O3 do not exist. We evaluated three O3 metrics - phytotoxic ozone dose (POD), accumulated ozone exposure over the threshold of 40 ppb h (AOT40), and the sum of all hourly average concentrations (SUM00) - for the Brazilian native tropical tree species Astronium graveolens Jacq. We used the DO3SE (Deposition of Ozone for Stomatal Exchange) model and calculated PODY for different thresholds (from 0 to 6 mmol O3 m(-2) PLA s(-1)), evaluating the model's performance through the relationship between measured and modelled conductance. The response parameters were: visible foliar injury, considered as incidence (% injured plants), severity (% injured leaves in relation to the number of leaves on injured plants), and leaf abscission. The model performance was suitable and significant (R(2) = 0.58; p < 0.001). POD0 was better correlated to incidence and leaf abscission, and SUM00 was better correlated to severity. The highest values of O3 concentration-based metrics (AOT40 and SUM00) did not coincide with those of POD0. Further investigation may improve the model and contribute to the proposition of a national standard for the protection of native species. PMID- 26805744 TI - Hydrothermal preparation of silver telluride nanostructures and photo-catalytic investigation in degradation of toxic dyes. AB - Different morphologies of Ag2Te nanostructures were synthesized using TeCl4 as a new precursor and hydrazine hydrate as reducing agent by a hydrothermal method. Various parameters that affect on morphology and purity of nanostructures were optimized. According to our experiments the best time and temperature for preparation of this nanostructure are 12 h and 120 degrees C. The photo catalytic behaviour of nanostructures in presence of UV-visible light for degradation of methyl orange was investigated. Results show that the presence of UV light is necessary for an efficient degradation of dye in aqueous solution. On the other hand, as observations propose the Ag2Te reveal a strong photoluminescence peak at room temperature that could be attributed to high level transition in the semiconductor. Nanostructures were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) techniques and UV-visible scanning spectrometer (UV-Vis). PMID- 26805746 TI - Using an Arrhenius-type function to describe temperature response of plant developmental processes: inference and cautions. PMID- 26805748 TI - Ultralow-power switching via defect engineering in germanium telluride phase change memory devices. AB - Crystal-amorphous transformation achieved via the melt-quench pathway in phase change memory involves fundamentally inefficient energy conversion events; and this translates to large switching current densities, responsible for chemical segregation and device degradation. Alternatively, introducing defects in the crystalline phase can engineer carrier localization effects enhancing carrier lattice coupling; and this can efficiently extract work required to introduce bond distortions necessary for amorphization from input electrical energy. Here, by pre-inducing extended defects and thus carrier localization effects in crystalline GeTe via high-energy ion irradiation, we show tremendous improvement in amorphization current densities (0.13-0.6 MA cm(-2)) compared with the melt quench strategy (~50 MA cm(-2)). We show scaling behaviour and good reversibility on these devices, and explore several intermediate resistance states that are accessible during both amorphization and recrystallization pathways. Existence of multiple resistance states, along with ultralow-power switching and scaling capabilities, makes this approach promising in context of low-power memory and neuromorphic computation. PMID- 26805749 TI - Supramolecular phosphate transfer catalysis by pillar[5]arene. AB - A kinetic study on dinitrophenylphosphate monoester hydrolysis in the presence of a cationic pillararene, P5A, has been carried out. Formation of the supramolecular complex between phosphate ester and P5A has been studied by NMR showing complexation-induced upfield proton shifts indicative of aromatic ring inclusion in the pillararene cavity. Molecular dynamic calculations allow structure characterization for the 1 : 1 and 1 : 2 complexes. As a result of the supramolecular interaction both the acidity of DNPP and its hydrolysis rate constants are increased. Catalysis results from combination of both electrostatic stabilization reducing the negative electron density on the PO3(=) oxygens and monoester dianion destabilization by the steric effects of close NMe3(+) groups hindering the hydrogen-bonding with water and destabilising the monoester dianion. PMID- 26805750 TI - Long-Term Evaluation of the Ambulatory Geriatric Assessment: A Frailty Intervention Trial (AGe-FIT): Clinical Outcomes and Total Costs After 36 Months. AB - OBJECTIVE: To compare the effects of care based on comprehensive geriatric assessment (CGA) as a complement to usual care in an outpatient setting with those of usual care alone. The assessment was performed 36 months after study inclusion. DESIGN: Randomized, controlled, assessor-blinded, single-center trial. SETTING: A geriatric ambulatory unit in a municipality in the southeast of Sweden. PARTICIPANTS: Community-dwelling individuals aged >= 75 years who had received inpatient hospital care 3 or more times in the past 12 months and had 3 or more concomitant medical diagnoses were eligible for study inclusion. Participants were randomized to the intervention group (IG) or control group (CG). INTERVENTION: Participants in the IG received CGA-based care for 24 to 31 months at the geriatric ambulatory unit in addition to usual care. OUTCOME MEASURES: Mortality, transfer to nursing home, days in hospital, and total costs of health and social care after 36 months. RESULTS: Mean age (SD) of participants was 82.5 (4.9) years. Participants in the IG (n = 208) lived 69 days longer than did those in the CG (n = 174); 27.9% (n = 58) of participants in the IG and 38.5% (n = 67) in the CG died (hazard ratio 1.49, 95% confidence interval 1.05-2.12, P = .026). The mean number of inpatient days was lower in the IG (15.1 [SD 18.4]) than in the CG (21.0 [SD 25.0], P = .01). Mean overall costs during the 36-month period did not differ between the IG and CG (USD 71,905 [SD 85,560] and USD 65,626 [SD 66,338], P = .43). CONCLUSIONS: CGA-based care resulted in longer survival and fewer days in hospital, without significantly higher cost, at 3 years after baseline. These findings add to the evidence of CGA's superiority over usual care in outpatient settings. As CGA-based care leads to important positive outcomes, this method should be used more extensively in the treatment of older people to meet their needs. PMID- 26805751 TI - Burden of Potentially Harmful Medications and the Association With Quality of Life and Mortality Among Institutionalized Older People. AB - OBJECTIVES: This study investigated the overlap among 3 different definitions of potentially harmful medication (PHM) use and the corresponding associations with resident quality of life and mortality. DESIGN: Cross-sectional study with 3-year follow-up for mortality. SETTING: Assisted living facilities and nursing homes in Helsinki and Kouvola, Finland. PARTICIPANTS: A total of 326 residents. MEASUREMENTS: PHM use was defined as (1) use of medications with anticholinergic properties, (2) use of Beers Criteria medications, and (3) concomitant use 3 or more psychotropic medications. Health-related quality of life (HRQoL) was assessed using the 15D and psychological well-being (PWB) scale. Residents self rated their own health using a 4-point scale. Mortality data were obtained from central registers. RESULTS: There were 38.0%, 28.2%, and 12.6% of residents who used PHMs according to 1 (G1), 2 (G2), and 3 definitions (G3), respectively. Overall, 21.2% of residents did not use PHMs according to any of the 3 definitions (G0). There were no significant differences in comorbidity, cognition, or functioning among groups. In adjusted analyses, there was a stepwise association between use of multiple PHMs and poorer self-rated health, poorer PWB, and poorer HRQoL. There was no association in adjusted analyses between PHM use and 3-year mortality (47.8%-63.8%). CONCLUSION: PHM use is highly prevalent in institutional settings, regardless of the definition of inappropriateness. Residents who used multiple categories of PHMs were at greatest risk of poor HRQoL, poor PWB, and poor self-rated health. However, there was no apparent association with increased mortality. Given the importance of quality of life as an outcome to older people, further efforts are needed to minimize PHM use in this setting. PMID- 26805752 TI - Identification of Older People at Risk of ADL Disability Using the Life-Space Assessment: A Longitudinal Cohort Study. AB - OBJECTIVES: Life-space mobility, assessed with the Life-Space Assessment (LSA), reflects an individual's mobility in terms of the spatial area, frequency, and need for assistance. The aims were to study associations between life-space mobility and disability status in activities of daily living (ADL), and to define cutoff scores for baseline LSA and LSA change over time identifying individuals who developed ADL inability during 2 years of follow-up. Robustness of the cutoff scores was tested accounting for potential confounders. DESIGN: Longitudinal analyses of the "Life-space mobility in old age" cohort study. SETTING: Home based interviews at baseline and phone interviews 2 years later. PARTICIPANTS: A total of 755 community-dwelling 75- to 90-year-old people living in Central Finland. MEASUREMENTS: LSA score (range 0-120) and ADL disability status (no difficulty, difficulty in >=1 tasks, or inability in >=1 tasks) were determined based on self-reports. RESULTS: Participants who developed difficulty or inability in ADL over time presented lower LSA scores at baseline and larger declines compared to those who remained without task difficulty or inability during the follow-up, respectively. Sensitivity and specificity analyses showed that baseline LSA <=52.3 (0.86 and 0.74, respectively) and LSA decline of >11.7 (0.76 and 0.71, respectively) identified participants who developed ADL inability over the follow-up. Multinomial regression showed that, after adjustment for potential confounders, these cutoff scores increased the odds to develop new difficulty in ADL tasks, and the odds to develop ADL inability among those with baseline difficulty. CONCLUSION: Our results suggest that restrictions and declines in life-space mobility may be early signs of increasing vulnerability to disability in old age. These longitudinally defined cutoff points may help to find clinical applications for the LSA. PMID- 26805753 TI - Frailty: An Emerging Public Health Priority. AB - The absolute and relative increases in the number of older persons are evident worldwide, from the most developed countries to the lowest-income regions. Multimorbidity and need for social support increase with age. Age-related conditions and, in particular, disabilities are a significant burden for the person, his or her family, and public health care systems. To guarantee the sustainability of public health systems and improve the quality of care provided, it is becoming urgent to act to prevent and delay the disabling cascade. Current evidence shows that too large a proportion of community-dwelling older people present risk factors for major health-related events and unmet clinical needs. In this scenario, the "frailty syndrome" is a condition of special interest. Frailty is a status of extreme vulnerability to endogenous and exogenous stressors exposing the individual to a higher risk of negative health-related outcomes. Frailty may represent a transition phase between successful aging and disability, and a condition to target for restoring robustness in the individual at risk. Given its syndromic nature, targeting frailty requires a comprehensive approach. The identification of frailty as a target for implementing preventive interventions against age-related conditions is pivotal. Every effort should be made by health care authorities to maximize efforts in this field, balancing priorities, needs, and resources. Raising awareness about frailty and age-related conditions in the population is important for effective prevention, and should lead to the promotion of lifelong healthy behaviors and lifestyle. PMID- 26805754 TI - Health Status and Morbidities in Resident Relatives of Patients With COPD. AB - OBJECTIVES: Resident relatives of patients with chronic obstructive pulmonary disease (COPD) may play a major role in obtaining a healthy lifestyle for patients. Little is known about resident relatives. This study aimed to compare health status, morbidities, care dependency, and mobility between patients with COPD and their resident relatives. DESIGN: Cross-sectional study. PARTICIPANTS: Stable patients with moderate to very severe COPD (n = 194) and their resident relatives (n = 194) were visited in their home environment. MEASUREMENTS: Post bronchodilator spirometry was assessed and generic health status was measured using the EuroQol-5 Dimensions and the Assessment of Quality of Life with 8 dimensions. Care dependency was measured using the Care Dependency Scale. Mobility was measured using the Timed "Up and Go" test (TUG). Morbidities (COPD, hypertension, anxiety and depression, obesity, and muscle wasting) were determined using accepted disease cutoff points and/or receiving specific treatment. RESULTS: Age (patients: 66.0 [8.7], resident relatives: 64.8 [9.7]) and gender (male patients: 53%, male resident relatives: 45%) were comparable. Patients had worse generic health status, higher level of care dependency, and worse mobility. 29% of the resident relatives had airflow limitation based on the Tiffeneau index and 19% based on the lower limit of normal, 33% were current smokers, and 92% had at least one chronic condition. Resident relatives more frequently had hypertension (46% versus 69%). CONCLUSION: Resident relatives of patients with COPD are often current smokers and often have undiagnosed morbidities. Although their health status is better compared with patients, their disease management and health behavior should also be considered when advising patients in obtaining a healthier lifestyle and also when involving them as informal caregivers. PMID- 26805755 TI - Combining geometric morphometrics with molecular genetics to investigate a putative hybrid complex: a case study with barbels Barbus spp. (Teleostei: Cyprinidae). AB - This integrative study examined the morphological and genetic affinities of three endemic barbel species from Italy (brook barbel Barbus caninus, Italian barbel Barbus plebejus and horse barbel Barbus tyberinus) and of putative hybrid specimens to their species of origin. Two of the species frequently occur together with the non-native barbel Barbus barbus. DNA barcoding indicates that mitochondrial (mt) haplotypes often do not match the species expected from morphology. Linear distance measurements and meristics are not informative for discrimination of the species and putative hybrids, but a discriminant analysis of principal components (DAPC) of geometric landmark data produces reassignments largely in congruence with mt and nuclear genetic data. Cyto-nuclear conflicts confirm the presence of hybridization in B. plebejus and B. tyberinus and identify additional introgressed specimens. A comparison between mixed genotypes and their morphology-based assignment reveals no predictable pattern. The finding that most individuals of the morphologically similar B. plebejus and B. tyberinus have very high assignment probabilities to their respective species suggests that the presented approach may serve as a valuable tool to distinguish morphologically very similar taxa. PMID- 26805756 TI - Expression and purification of recombinant proteins in Escherichia coli tagged with the metal-binding protein CusF. AB - Production of recombinant proteins in Escherichia coli has been improved considerably through the use of fusion proteins, because they increase protein solubility and facilitate purification via affinity chromatography. In this article, we propose the use of CusF as a new fusion partner for expression and purification of recombinant proteins in E. coli. Using a cell-free protein expression system, based on the E. coli S30 extract, Green Fluorescent Protein (GFP) was expressed with a series of different N-terminal tags, immobilized on self-assembled protein microarrays, and its fluorescence quantified. GFP tagged with CusF showed the highest fluorescence intensity, and this was greater than the intensities from corresponding GFP constructs that contained MBP or GST tags. Analysis of protein production in vivo showed that CusF produces large amounts of soluble protein with low levels of inclusion bodies. Furthermore, fusion proteins can be exported to the cellular periplasm, if CusF contains the signal sequence. Taking advantage of its ability to bind copper ions, recombinant proteins can be purified with readily available IMAC resins charged with this metal ion, producing pure proteins after purification and tag removal. We therefore recommend the use of CusF as a viable alternative to MBP or GST as a fusion protein/affinity tag for the production of soluble recombinant proteins in E. coli. PMID- 26805757 TI - Customized humanoptics silicone iris prosthesis in eyes with posttraumatic iris loss: outcomes and complications. AB - PURPOSE: Posttraumatic partial or total iris defects often cause significant debilitating glare, photophobia, decreased vision and cosmetic problems. Currently, the best cosmetic results can be obtained with a customized silicone iris prosthesis. However, little is known about the functional results and the rate of complication if this type of iris prosthesis is implanted into severely traumatized eyes. The aim of this study is to analyse the functional and cosmetic outcomes as well as complications after Artificial Iris implantation. METHODS: A consecutive series of 34 patients who received a customized silicone iris prosthesis after severe globe injury with total or sub-total iris loss was analysed retrospectively. Additionally, patients were interviewed regarding change in subjective complaints. RESULTS: Median follow-up was 24 months (range 12.0-48.8). Mean visual acuity prior to Artificial Iris implantation was 1.1 logMAR (range 0.3-2.6). Five patients (15%) had pre-existing glaucoma and eight patients (24%) had pre-existing hypotony. Visual acuity 12 months after surgery was 1.4 logMAR (range 0.2-2.6). Complications included newly diagnosed glaucoma in three eyes (9%) and hypotony in three eyes (9%), persisting intraocular inflammation or macular oedema in seven patients (21%), and corneal endothelial decompensation requiring corneal transplantation in six patients (18%). Patients' satisfaction increased by reducing glare and enhanced cosmetic appearance. CONCLUSION: The customized silicone iris prosthesis is an individualized treatment approach with appealing cosmetic results. Therefore, especially traumatized eyes with highly different posttraumatic conditions could benefit. However, in some patients, the implantation of this device may cause an increase of intraocular pressure, corneal endothelial decompensation or persisting inflammation. PMID- 26805758 TI - Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease. AB - Multicentric Castleman disease (MCD) describes a heterogeneous group of disorders involving systemic inflammation, characteristic lymph node histopathology, and multi-organ dysfunction because of pathologic hypercytokinemia. Whereas Human Herpes Virus-8 (HHV-8) drives the hypercytokinemia in a cohort of immunocompromised patients, the etiology of HHV-8-negative MCD is idiopathic (iMCD). Recently, a limited series of iMCD cases in Japan sharing a constellation of clinical features, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been described as TAFRO syndrome. Herein, we report clinicopathological findings on 25 patients (14 males and 11 females; 23 Japanese-born and two US-born), the largest TAFRO syndrome case series, including the first report of cases from the USA. The median age of onset was 50 years old (range: 23-72). The frequency of each feature was as follows: thrombocytopenia (21/25), anasarca (24/25), fever (21/25), organomegaly (25/25), and reticulin fibrosis (13/16). These patients frequently demonstrated abdominal pain, elevated serum alkaline phosphatase levels, and acute kidney failure. Surprisingly, none of the cases demonstrated marked hypergammoglobulinemia, which is frequently reported in iMCD. Lymph node biopsies revealed atrophic germinal centers with enlarged nuclei of endothelial cells and proliferation of endothelial venules in interfollicular zone. 23 of 25 cases were treated initially with corticosteroids; 12 patients responded poorly and required further therapy. Three patients died during the observation period (median: 9 months) because of disease progression or infections. TAFRO syndrome is a unique subtype of iMCD that demonstrates characteristic clinicopathological findings. Further study to clarify prognosis, pathophysiology, and appropriate treatment is needed. PMID- 26805760 TI - Unraveling the roles of Atg4 proteases from autophagy modulation to targeted cancer therapy. AB - Atg4 proteases are cysteine proteases, which are well known for their crucial roles in the lipidation and delipidation of LC3 during the autophagy process. At least four human Atg4 homologs have been reported according to their sequence homology to the yeast Saccharomyces cerevisiae (Sc) Atg4. Accumulating evidence has recently indicated that abnormal expression levels of some human Atg4 proteins occur in several types of cancer cells, which may be closely related to tumor progression, tumor suppression and cancer therapy resistance. In this review, we focus on highlighting the pivotal roles of the human Atg4 proteases in the LC3 conjugation system and their major function in autophagy. Moreover, we further explore the roles of human Atg4 proteases as potential novel targets for cancer therapy. Taken together, these findings would shed light on elucidating the key roles of Atg4 proteases from autophagy modulation to targeted cancer therapy. PMID- 26805759 TI - Cisplatin enhances NK cells immunotherapy efficacy to suppress HCC progression via altering the androgen receptor (AR)-ULBP2 signals. AB - The aim of this study is to investigate the influence of cisplatin on the efficacy of natural killer (NK) cells immunotherapy to suppress HCC progression, and provide valuable information on better application of cisplatin in clinical settings. By using in vitro cell cytotoxicity test and in vivo liver orthotopic xenograft mice model, we identified the role of cisplatin in modulating NK cells cytotoxicity. Luciferase report assay and chromatin immunoprecipitation assay were applied for mechanism dissection. Immunohistochemistry is performed for sample staining. We found cisplatin could enhance the efficacy of NK cells immunotherapy to better suppress HCC progression via altering the androgen receptor (AR)-UL16-binding protein 2 (ULBP2) signals both in vitro and in vivo. Mechanism dissection revealed that cisplatin could suppress AR expression via two distinct ways: increasing miR-34a-5p to suppress AR expression and altering the ubiquitination to accelerate the AR protein degradation. The suppressed AR might then function through up-regulating ULBP2, a natural-killer group 2 member D ligand, to enhance the cytotoxicity of NK cells. Together, these results indicated an unrecognized favoring effect of cisplatin in HCC treatment. By suppressing AR in HCC, cisplatin could up-regulate cytotoxicity of NK cells to better target HCC. This finding may provide a potential new approach to control HCC by combining traditional chemotherapy with immunotherapy. PMID- 26805761 TI - VEGF/NRP-1axis promotes progression of breast cancer via enhancement of epithelial-mesenchymal transition and activation of NF-kappaB and beta-catenin. AB - Autocrine vascular endothelial growth factor (VEGF) can regulate the survival and progression of cancers through its various receptors. But the mechanisms and mediators for these functions are largely uncovered, especially in breast cancer. We examined the potential roles and mechanisms of VEGF/neuropilin-1 (NRP-1) axis in regulating the tumorigenesis and metastasis of breast cancer and found the expression of VEGF and NRP-1 correlated with aggressiveness of breast cancer. Knockdown of VEGF or NRP-1 inhibited the proliferation, migration and invasion, but enhanced the apoptosis of MDA-MB-231 cells. In contrast, induction of NRP-1 over-expression promoted the proliferation, migration and invasion of MCF-7 cells. VEGF or NRP-1 silencing attenuated the epithelial-mesenchymal transition (EMT) process and the activation of NF-kappaBp65, but enhanced GSK-3beta expression in MDA-MB-231 cells while NRP-1 over-expression reversed the effects in MCF-7 cells. Treatment with hVEGF165 did not change the inhibition in NRP-1 silencing MDA-MB-231 cells, but enhanced the aggressiveness of NRP-1 over expressing MCF-7 cells. In addition, VEGF-silencing inhibited the growth and metastasis of implanted MDA-MB-231 tumors in vivo. Our novel data suggest that the positive regulation of the VEGF/NRP-1 axis on the tumorigenesis and metastasis of breast cancer may be associated with enhancing the EMT process and the NF-kappaB and beta-catenin signaling. Hence, the VEGF/NRP-1 axis may be a valuable target for design of therapies for intervention of breast cancer. PMID- 26805762 TI - Mitotic regulator Nlp interacts with XPA/ERCC1 complexes and regulates nucleotide excision repair (NER) in response to UV radiation. AB - Cellular response to DNA damage, including ionizing radiation (IR) and UV radiation, is critical for the maintenance of genomic fidelity. Defects of DNA repair often result in genomic instability and malignant cell transformation. Centrosomal protein Nlp (ninein-like protein) has been characterized as an important cell cycle regulator that is required for proper mitotic progression. In this study, we demonstrate that Nlp is able to improve nucleotide excision repair (NER) activity and protects cells against UV radiation. Upon exposure of cells to UVC, Nlp is translocated into the nucleus. The C-terminus (1030-1382) of Nlp is necessary and sufficient for its nuclear import. Upon UVC radiation, Nlp interacts with XPA and ERCC1, and enhances their association. Interestingly, down regulated expression of Nlp is found to be associated with human skin cancers, indicating that dysregulated Nlp might be related to the development of human skin cancers. Taken together, this study identifies mitotic protein Nlp as a new and important member of NER pathway and thus provides novel insights into understanding of regulatory machinery involved in NER. PMID- 26805763 TI - Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer cell motility. AB - Desmoplasia and hypoxia in pancreatic cancer mutually affect each other and create a tumor-supportive microenvironment. Here, we show that microenvironment remodeling by hypoxic pancreatic stellate cells (PSCs) promotes cancer cell motility through alteration of extracellular matrix (ECM) fiber architecture. Three-dimensional (3-D) matrices derived from PSCs under hypoxia exhibited highly organized parallel-patterned matrix fibers compared with 3-D matrices derived from PSCs under normoxia, and promoted cancer cell motility by inducing directional migration of cancer cells due to the parallel fiber architecture. Microarray analysis revealed that procollagen-lysine, 2-oxoglutarate 5 dioxygenase 2 (PLOD2) in PSCs was the gene that potentially regulates ECM fiber architecture under hypoxia. Stromal PLOD2 expression in surgical specimens of pancreatic cancer was confirmed by immunohistochemistry. RNA interference mediated knockdown of PLOD2 in PSCs blocked parallel fiber architecture of 3-D matrices, leading to decreased directional migration of cancer cells within the matrices. In conclusion, these findings indicate that hypoxia-induced PLOD2 expression in PSCs creates a permissive microenvironment for migration of cancer cells through architectural regulation of stromal ECM in pancreatic cancer. PMID- 26805764 TI - Intracellular autocrine VEGF signaling promotes EBDC cell proliferation, which can be inhibited by Apatinib. AB - Tumor cells produce vascular endothelial growth factor (VEGF) which can interact with membrane or cytoplasmic VEGF receptors (VEGFRs) to promote cell growth. We aimed to investigate the role of extracellular/intracellular autocrine VEGF signaling and Apatinib, a highly selective VEGFR2 inhibitor, in extrahepatic bile duct cancer (EBDC). We found conditioned medium or recombinant human VEGF treatment promoted EBDC cell proliferation through a phospholipase C-gamma1 dependent pathway. This pro-proliferative effect was diminished by VEGF, VEGFR1 or VEGFR2 neutralizing antibodies, but more significantly suppressed by intracellular VEGFR inhibitor. The rhVEGF induced intracellular VEGF signaling by promoting nuclear accumulation of pVEGFR1/2 and enhancing VEGF promoter activity, mRNA and protein expression. Internal VEGFR2 inhibitor Apatinib significantly inhibited intracellular VEGF signaling, suppressed cell proliferation in vitro and delayed xenograft tumor growth in vivo, while anti-VEGF antibody Bevacizumab showed no effect. Clinically, overexpression of pVEGFR1 and pVEGFR2 was significantly correlated with poorer overall survival (P = .007 and P = .020, respectively). In conclusion, the intracellular autocrine VEGF loop plays a predominant role in VEGF-induced cell proliferation. Apatinib is an effective intracellular VEGF pathway blocker that presents a great therapeutic potential in EBDC. PMID- 26805765 TI - Gender differences in the clinical course of Finnish gelsolin amyloidosis. AB - PURPOSE: To investigate gender differences in Finnish gelsolin amyloidosis (AGel amyloidosis). PATIENTS AND METHODS: AGel amyloidosis patients, who were members of Finnish Amyloidosis Association (SAMY), filled in a questionnaire compiling known and suspected aspects of their disease. Telephone interviews and hospital medical records, when available, complemented the questionnaire. The data were entered to the database in order to create a national AGel amyloidosis patient registry (FIN-GAR). RESULTS: A total of 227 patients, 156 women and 71 men, participated in the study. The women in our registry noticed their first symptoms at the median age of 39 years versus 43 years for men (p = 0.01). At the age in which the diagnosis was made there was a trend to be observed between men and women (women: 39 years versus men: 43 years, p = 0.053). Corneal lattice dystrophy was diagnosed in significantly younger women than men (median ages 41 versus 49 years, respectively, p = 0.01). Of other ophthalmological manifestations, corneal ulcer, impaired vision and glaucoma were all diagnosed at least 5 years earlier in women, although differences were not statistically significant. Ophthalmological manifestations, such as dry eyes and corneal ulcer; dermatological signs, such as blepharochalasis, and also neurological symptoms, such as myokymia and carpal tunnel syndrome, were more prevalent among women. CONCLUSIONS: In the largest so far available study on AGel amyloidosis we show that women developed symptoms and signs of AGel amyloidosis at younger age. Especially eye-related problems occurred earlier and together with nerve and skin manifestations, the characteristic clinical triad in AGel amyloidosis, were more common in women. However, a clear limitation of our study was a selection bias caused by a significant underrepresentation of men in the study population. PMID- 26805766 TI - Low protein diet during gestation and lactation increases food reward seeking but does not modify sucrose taste reactivity in adult female rats. AB - INTRODUCTION: Nutritional deficiencies during neural development may lead to irreversible changes, even after nutritional rehabilitation, promoting morphological and functional adaptations of structures involved with various behaviours including feeding behaviour. However, the ability of the exposure low protein diet during gestation and lactation to affect the hedonic component of food intake is still poorly understood, especially in females. METHODS: Wistar rats were divided into two groups according to the diet offered to the dams during pregnancy and lactation: control female (CF; diet with 17% protein, n=7) and low protein female (LPF; diet with 8% protein, n=7). The following parameters were evaluated: (a) body weight during weaning, 30, 45, 60, 75, 90 days of life; (b) standard diet intake from 110 to 132 days of life; (c) fat diet and consumption of simple carbohydrates (HFHS) for 1h at 145 days of life; (d) incentive runway task 60 days after 82 days of life; (e) taste reactivity at 90 days of life; and (f) neuronal activation in the caudate putamen, amygdala, paraventricular nucleus of the hypothalamus under stimulus HFHS at 145 days of life. RESULTS: The exposure, a low protein diet during gestation and lactation, decreased the body weight throughout the study period from weaning to 90 days of life. However, there was no significant change in the body weight of low protein females from 110 to 132 days of life compared with the control females. There was an increase in the rate of the search for reward and reduced the latency of the perception of bitter taste. The exposure, a low protein diet during gestation and lactation, also promoted hypophagy in adult females compared with control animals. The low protein female had increased HFHS diet consumption compared with the control. Undernutrition increased neuronal activation in response to HFHS diet consumption compared with female controls in the amygdala and in the caudate putamen. CONCLUSION: Females subjected to the exposure, a low protein diet during gestation and lactation, exhibit hypophagy on a standard diet but a higher consumption of a diet rich in lipids and simple carbohydrates. And also were more motivated by the pursuit of reward and reduced latency of the bitter taste reactivity, and increased the number of immunoreactive cells c-fos protein activated in the caudate putamen, amygdala and paraventricular nucleus. PMID- 26805768 TI - Effect of continuous aerobic vs. interval training on selected anthropometrical, physiological and functional parameters of adults with Down syndrome. AB - BACKGROUND: A large percentage of adults with Down syndrome (DS) are overweight and have extremely low aerobic capacities compared with the general population and persons with intellectual disability without DS. Previous aerobic training intervention studies showed limited potential to significantly ameliorate anthropometrical and cardiovascular variables. The primary purpose of this study was to determine the effect of continuous aerobic training (CAT) vs. interval training (IT) on selected anthropometrical, health, physical and functional parameters of adults with DS. METHODS: Forty-two adults with DS (25 men and 17 women) and a mean age of 33.8 (+/-8.6) years were randomly allocated to one of three groups (IT, CAT and control). Training was performed for 12 weeks. The IT group performed 10-30 s all out sprints with 90 s (1:3 work-rest ratio) of low cadence, low intensity cycling or walking. The CAT group performed continuous cycling and walking at an intensity of 70-80% of VO2 peak. Heart rate monitors were used for monitoring training intensities. After 6 weeks of training, the intensity of the CAT was increased to 85% of VO2 peak, whilst the intensity of the IT group remained 'all out'. An increase of 5 min in duration was implemented after 6 weeks for both training groups. To evaluate pre-post differences between groups, a repeated analysis of covariance with post hoc Bonferroni test was performed RESULTS: After 12 weeks of training, body weight and body mass index decreased significantly more in the IT group compared with control and CAT (P < 0.05). Participants in the IT group decreased their body weight from 71.4 +/- 8 to 69.4 +/- 8 kg and their body mass index from 29.3 +/- 4 to 28.5 +/- 4 kg/m2 . Significant ameliorations for functional parameters and leg strength were shown for CAT compared with control (P < 0.05). Participants in the CAT group improved their performance in the 6 minute walk distance (499 +/- 78 to 563 +/- 75 m), 8 ft up-and-go (5.9 +/- 1.2 to 4.8 +/- 0.9) and leg strength (13.1 +/- 2 to 15.2 +/ 2). VO2 peak and time to exhaustion significantly improved in both the IT and CAT group compared with control (P < 0.01). Moreover, a significant improvement for relative VO2 peak was also determined for IT compared with CAT (P < 0.05). Participants in the IT group increased their VO2 peak from 32 +/- 8 to 37 +/- 8 mL/min/kg. Submaximal heart rate and VO2 values improved significantly within both exercise groups (P < 0.05). CONCLUSION: Interval training and CAT can both be pursued by adults with DS to positively impact on various parameters of anthropometry, fitness and functional ability, with IT more appropriate for improving body weight and aerobic capacity. PMID- 26805770 TI - Independent Association of Vitamin D With Physical Function in People With Chronic Spinal Cord Injury. AB - OBJECTIVE: To explore the relation between vitamin D and physical function outcomes in people with spinal cord injury (SCI). DESIGN: Cross-sectional study. SETTING: Rehabilitation institute. PARTICIPANTS: Consecutive patients (N=100; 72 men and 28 women) with chronic SCI admitted to a rehabilitation program. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional independence in activities of daily living (ADL) and leisure time physical activity (LTPA) were assessed as measures of physical function. RESULTS: Vitamin D deficiency (<20ng/mL) was found in 78 patients: they exhibited a significantly higher body mass index, lower functional independence in ADL, and were engaged in a significantly poorer weekly LTPA. At the linear multiple regression analysis, lower 25-hydroxyvitamin D levels showed significant independent associations with poorer functional independence in ADL (beta=.59; 95% confidence interval, .36 .82; P<.0001) and with poorer LTPA (beta=2.35; 95% confidence interval, 0.77 3.94; P=.004), after adjustment for other predictors of physical function outcomes selected by univariate analyses. CONCLUSIONS: In people with chronic SCI, a low vitamin D level represents an independent predictor of poor physical function. PMID- 26805773 TI - Self-Associating Behavior of Acetone in Liquid Krypton. AB - Acetone molecules are inclined to self-associate through dipole-dipole interactions because of their large dipole moment. Infrared spectroscopy of compounds dissolved in liquid noble gases supported by high level ab initio calculations allows investigating the self-associating behavior and determining the thermodynamical properties. In this study, infrared spectra of various concentrations of acetone dissolved in liquid krypton are recorded at constant temperature. Overlapping monomer and dimer spectra are separated by analyzing the obtained data sets with numerical methods based on least-squares fitting. Although acetone is known to self-associate, only a few spectral features have been presented in literature before. In this study, the application of new numerical approaches succeeds in resolving overlapping spectra and allows observing isolated acetone dimer absorption bands for the complete mid infrared spectrum. By use of data sets of spectra recorded at temperatures between 134 and 142 K, the experimental standard dimerization enthalpy was determined to be -10.8 kJ mol(-1). MP2/aug-cc-pVDZ calculations predicted a stacked and planar dimer geometry of which the stacked geometry is more stable. Combining MP2 energies and single point corrections involving CCSD(T) calculations and complete basis set extrapolations based on the MP2/aug-cc-pVDZ equilibrium geometry lead to complexation energy of -28.4 kJ mol(-1) for the stacked geometry and -15.1 kJ mol(-1) for the planar geometry. The corresponding values for the complexation enthalpies in solution, obtained by combining these values with corrections for thermal and solvent influences are -13.7 and -5.8 kJ mol(-1). PMID- 26805775 TI - Inkjet Color Printing by Interference Nanostructures. AB - Color printing technology is developing rapidly; in less than 40 years, it moved from dot matrix printers with an ink-soaked cloth ribbon to 3D printers used to make three-dimensional color objects. Nevertheless, what remained unchanged over this time is the fact that in each case, dye inks (CMYK or RGB color schemes) were exclusively used for coloring, which inevitably limits the technological possibilities and color reproduction. As a next step in printing color images and storing information, we propose the technology of producing optical nanostructures. In this paper, we report use of inkjet technology to create colored interference layers with high accuracy without the need for high temperature fixing. This was made possible due to using titania-based colloidal ink yielding monolithic coatings with a high refractive index (2.00 +/- 0.08 over the entire visible range) when naturally dried. By controlling the film thickness by using inkjet deposition, we produced images based on controlled interference and implementing color printing with one ink. The lack of dyes in the proposed method has good environmental prospects, because applied systems based on a crystalline anatase sol are nontoxic and biologically inert. The paper explains in detail the principle of producing interference images by the classical inkjet method and shows the advantages of this technique in depositing coatings with uniform thickness, which are required for large-scale interference color imaging even on unprepared polymer films. This article demonstrates the possibility of inkjet printing of nanostructures with a precision in thickness of up to 50 nm, we believe that the proposed approach will be the groundwork for developing interference color printing approach and allow to implement new methods of forming optical nano-objects by widely available techniques. PMID- 26805771 TI - Maternal and paternal genetic diversity of ancient sheep in Estonia from the Late Bronze Age to the post-medieval period and comparison with other regions in Eurasia. AB - Sheep were among the first domesticated animals to appear in Estonia in the late Neolithic and became one of the most widespread livestock species in the region from the Late Bronze Age onwards. However, the origin and historical expansion of local sheep populations in Estonia remain poorly understood. Here, we analysed fragments of the hypervariable D-loop of mitochondrial DNA (mtDNA; 213 bp) and the Y-chromosome SRY gene (130 bp) extracted from 31 archaeological sheep bones dated from approximately 800 BC to 1700 AD. The ancient DNA data of sheep from Estonia were compared with ancient sheep from Finland as well as a set of contemporary sheep breeds from across Eurasia in order to place them in a wider phylogeographical context. The analysis shows that: (i) 24 successfully amplified and analysed mtDNA sequences of ancient sheep cluster into two haplogroups, A and B, of which B is predominant; (ii) four of the ancient mtDNA haplotypes are novel; (iii) higher mtDNA haplotype diversity occurred during the Middle Ages as compared to other periods, a fact concordant with the historical context of expanding international trade during the Middle Ages; (iv) the proportion of rarer haplotypes declined during the expansion of sheep from the Near Eastern domestication centre to the northern European region; (v) three male samples showed the presence of the characteristic northern European haplotype, SNP G-oY1 of the Y-chromosome, and represent the earliest occurrence of this haplotype. Our results provide the first insight into the genetic diversity and phylogeographical background of ancient sheep in Estonia and provide basis for further studies on the temporal fluctuations of ancient sheep populations. PMID- 26805776 TI - Iron-catalyzed arylation of alpha-aryl-alpha-diazoesters. AB - An iron-catalyzed arylation of alpha-aryl-alpha-diazoesters with electron-rich benzene rings was developed, which provides an efficient method for the preparation of 1,1-diarylacetates with high yields and excellent chemo- and regio selectivities. PMID- 26805777 TI - From big data to deep insight in developmental science. AB - The use of the term 'big data' has grown substantially over the past several decades and is now widespread. In this review, I ask what makes data 'big' and what implications the size, density, or complexity of datasets have for the science of human development. A survey of existing datasets illustrates how existing large, complex, multilevel, and multimeasure data can reveal the complexities of developmental processes. At the same time, significant technical, policy, ethics, transparency, cultural, and conceptual issues associated with the use of big data must be addressed. Most big developmental science data are currently hard to find and cumbersome to access, the field lacks a culture of data sharing, and there is no consensus about who owns or should control research data. But, these barriers are dissolving. Developmental researchers are finding new ways to collect, manage, store, share, and enable others to reuse data. This promises a future in which big data can lead to deeper insights about some of the most profound questions in behavioral science. PMID- 26805778 TI - Injectable hybrid delivery system composed of gellan gum, nanoparticles and gentamicin for the localized treatment of bone infections. AB - OBJECTIVES: Bone infections are treated with antibiotics administered intravenously, antibiotic-releasing bone cements or collagen sponges placed directly in the infected area. These approaches render limited effectiveness due to the lack of site specificity and invasiveness of implanting cements and sponges. To address these limitations, we developed a novel polysaccharide hydrogel-based injectable system that enables controlled delivery of gentamicin (GENT). Its advantages are minimal invasiveness, and localized and finely regulated release of the drug. METHODS: GENT was incorporated both directly within the gellan gum hydrogel and into poly(L-lactide-co-glycolide) nanoparticles embedded into the hydrogel. RESULTS: We confirmed the injectability of the system and measured extrusion force was 15.6 +/- 1.0 N, which is suitable for injections. The system set properly after the injection as shown by rheological measurements. Desired burst release of the drug was observed within the first 12 h and the dose reached ~27% of total GENT. Subsequently, GENT was released gradually and sustainably: ~60% of initial dose within 90 days. In vitro studies confirmed antimicrobial activity of the system against Staphylococcus spp. and cytocompatibility with osteoblast-like cells. CONCLUSIONS: Developed injectable system enables minimally invasive, local and sustained delivery of the pharmaceutically relevant doses of GENT to combat bone infections. PMID- 26805779 TI - The Impact of Causal Explanations on Outcome in People Experiencing Psychosis: A Systematic Review. AB - : Findings suggest that the way an individual understands their experiences has important consequences on subsequent health behaviour. One aspect of an individual's understanding is what they believe has caused their experiences. This has been associated with treatment outcome and attitudes towards mental health problems. The aim of this systematic review was to examine the impact of causal beliefs on treatment outcome and stigma in people experiencing psychosis. Three main databases were searched and 21 articles that investigated various aspects of treatment outcome, and stigma in relation to causal beliefs was included in the review. Overall, there were a small number of replicated findings which limits the interpretation of results. There is an indication that causal explanations are associated with various treatment outcomes, including attitudes towards treatment and satisfaction with therapeutic relationships as well as internalized stigma. Spiritual beliefs appeared to be adopted as a coping mechanism and a way to reduce stigma but did not appear to be associated with treatment outcome. Individuals with psychosis do appear to develop causal beliefs that may be associated with engagement with services and treatment, as well as impacting on their attitudes towards themselves and others with mental illness. This may have important implications for clinical practice. Copyright (c) 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Individuals who have experience of psychosis develop their own subjective causal explanations, and these can be complex and contradictory. An individual's causal explanation may influence how they engage with services and treatment, as well as providing a way of coming to terms with their difficulties. Causal explanations may also contribute to the experience of stigma, which is often a significant barrier to recovery for this client group. PMID- 26805780 TI - Mitotic Intragenic Recombination: A Mechanism of Survival for Several Congenital Disorders of Glycosylation. AB - Congenital disorders of glycosylation (CDGs) are disorders of abnormal protein glycosylation that affect multiple organ systems. Because most CDGs have been described in only a few individuals, our understanding of the associated phenotypes and the mechanisms of individual survival are limited. In the process of studying two siblings, aged 6 and 11 years, with MOGS-CDG and biallelic MOGS (mannosyl-oligosaccharide glucosidase) mutations (GenBank: NM_006302.2; c.[65C>A; 329G>A] p.[Ala22Glu; Arg110His]; c.[370C>T] p.[Gln124(*)]), we noted that their survival was much longer than the previous report of MOGS-CDG, in a child who died at 74 days of age. Upon mutation analysis, we detected multiple MOGS genotypes including wild-type alleles in their cultured fibroblast and peripheral blood DNA. Further analysis of DNA from cultured fibroblasts of six individuals with compound heterozygous mutations of PMM2 (PMM2-CDG), MPI (MPI-CDG), ALG3 (ALG3-CDG), ALG12 (ALG12-CDG), DPAGT1 (DPAGT1-CDG), and ALG1 (ALG1-CDG) also identified multiple genotypes including wild-type alleles for each. Droplet digital PCR showed a ratio of nearly 1:1 wild-type to mutant alleles for most, but not all, mutations. This suggests that mitotic recombination contributes to the survival and the variable expressivity of individuals with compound heterozygous CDGs. This also provides an explanation for prior observations of a reduced frequency of homozygous mutations and might contribute to increased levels of residual enzyme activity in cultured fibroblasts of individuals with MPI- and PMM2-CDGs. PMID- 26805782 TI - Bi-allelic Truncating Mutations in TANGO2 Cause Infancy-Onset Recurrent Metabolic Crises with Encephalocardiomyopathy. AB - Molecular diagnosis of mitochondrial disorders is challenging because of extreme clinical and genetic heterogeneity. By exome sequencing, we identified three different bi-allelic truncating mutations in TANGO2 in three unrelated individuals with infancy-onset episodic metabolic crises characterized by encephalopathy, hypoglycemia, rhabdomyolysis, arrhythmias, and laboratory findings suggestive of a defect in mitochondrial fatty acid oxidation. Over the course of the disease, all individuals developed global brain atrophy with cognitive impairment and pyramidal signs. TANGO2 (transport and Golgi organization 2) encodes a protein with a putative function in redistribution of Golgi membranes into the endoplasmic reticulum in Drosophila and a mitochondrial localization has been confirmed in mice. Investigation of palmitate-dependent respiration in mutant fibroblasts showed evidence of a functional defect in mitochondrial beta-oxidation. Our results establish TANGO2 deficiency as a clinically recognizable cause of pediatric disease with multi-organ involvement. PMID- 26805781 TI - Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic Crises, and Cardiac Arrhythmia Due to Bi-allelic TANGO2 Mutations. AB - The underlying genetic etiology of rhabdomyolysis remains elusive in a significant fraction of individuals presenting with recurrent metabolic crises and muscle weakness. Using exome sequencing, we identified bi-allelic mutations in TANGO2 encoding transport and Golgi organization 2 homolog (Drosophila) in 12 subjects with episodic rhabdomyolysis, hypoglycemia, hyperammonemia, and susceptibility to life-threatening cardiac tachyarrhythmias. A recurrent homozygous c.460G>A (p.Gly154Arg) mutation was found in four unrelated individuals of Hispanic/Latino origin, and a homozygous ~34 kb deletion affecting exons 3-9 was observed in two families of European ancestry. One individual of mixed Hispanic/European descent was found to be compound heterozygous for c.460G>A (p.Gly154Arg) and the deletion of exons 3-9. Additionally, a homozygous exons 4-6 deletion was identified in a consanguineous Middle Eastern Arab family. No homozygotes have been reported for these changes in control databases. Fibroblasts derived from a subject with the recurrent c.460G>A (p.Gly154Arg) mutation showed evidence of increased endoplasmic reticulum stress and a reduction in Golgi volume density in comparison to control. Our results show that the c.460G>A (p.Gly154Arg) mutation and the exons 3-9 heterozygous deletion in TANGO2 are recurrent pathogenic alleles present in the Latino/Hispanic and European populations, respectively, causing considerable morbidity in the homozygotes in these populations. PMID- 26805785 TI - Competencies, milestones, and EPAs - Are those who ignore the past condemned to repeat it? AB - BACKGROUND: The idea of competency-based education sounds great on paper. Who wouldn't argue for a standardized set of performance-based assessments to assure competency in graduating students and residents? Even so, conceptual concerns have already been raised about this new system and there is yet no evidence to refute their veracity. AIMS: We argue that practical concerns deserve equal consideration, and present evidence strongly suggesting these concerns should be taken seriously. METHOD: Specifically, we share two historical examples that illustrate what happened in two disparate contexts (K-12 education and the Department of Defense [DOD]) when competency (or outcomes-based) assessment frameworks were implemented. We then examine how observation and assessment of clinical performance stands currently in medical schools and residencies, since these methodologies will be challenged to a greater degree by expansive lists of competencies and milestones. RESULTS/CONCLUSIONS: We conclude with suggestions as to a way forward, because clearly the assessment of competency and the ability to guarantee that graduates are ready for medical careers is of utmost importance. Hopefully the headlong rush to competencies, milestones, and core entrustable professional activities can be tempered before even more time, effort, frustration and resources are invested in an endeavor which history suggests will collapse under its own weight. PMID- 26805786 TI - Whole-body vibration therapy in intensive care patients: A feasibility and safety study. AB - BACKGROUND: Admission to the intensive care unit is associated with sustained loss of muscle mass, reduced quality of life and increased mortality. Early rehabilitation measures may counteract this process. New approaches to rehabilitation while the patient remains in bed are whole-body vibration alone and whole-body vibration with a dumbbell. The aims of this study are to determine the safety of whole-body vibration for patients admitted to the intensive care unit, and to compare the effects of these techniques in intensive care unit patients and healthy subjects. METHODS: Twelve intensive care unit patients and 12 healthy subjects using whole-body vibration for the first time were examined while lying in bed. First both groups performed whole body vibration over 3 min. In a second step whole body vibration with dumbbell was performed. In order to determine the safety of the training intensity, heart rate, oxygen saturation and blood pressure were measured. The study was approved by the Marburg ethics committee. RESULTS: There were minor reversible and transient increases in diastolic blood pressure (p = 0.005) and heart rate (p = 0.001) in the control group with whole-body vibration with a dumbbell. In intensive care patients receiving whole-body vibration alone, there were increases in diastolic blood pressure (p = 0.011) and heart rate (p < 0.001). CONCLUSION: This study demonstrates the feasibility of using whole-body vibration and whole-body vibration with a dumbbell for intensive care unit in-bed patients. No clinically significant safety problems were found. Whole-body vibration and whole-body vibration with a dumbbell might therefore be alternative methods for use in early in-bed rehabilitation, not only for hospitalized patients. PMID- 26805783 TI - Genome-wide Association Study of Platelet Count Identifies Ancestry-Specific Loci in Hispanic/Latino Americans. AB - Platelets play an essential role in hemostasis and thrombosis. We performed a genome-wide association study of platelet count in 12,491 participants of the Hispanic Community Health Study/Study of Latinos by using a mixed-model method that accounts for admixture and family relationships. We discovered and replicated associations with five genes (ACTN1, ETV7, GABBR1-MOG, MEF2C, and ZBTB9-BAK1). Our strongest association was with Amerindian-specific variant rs117672662 (p value = 1.16 * 10(-28)) in ACTN1, a gene implicated in congenital macrothrombocytopenia. rs117672662 exhibited allelic differences in transcriptional activity and protein binding in hematopoietic cells. Our results underscore the value of diverse populations to extend insights into the allelic architecture of complex traits. PMID- 26805784 TI - Autosomal-Recessive Hearing Impairment Due to Rare Missense Variants within S1PR2. AB - The sphingosine-1-phosphate receptors (S1PRs) are a well-studied class of transmembrane G protein-coupled sphingolipid receptors that mediate multiple cellular processes. However, S1PRs have not been previously reported to be involved in the genetic etiology of human traits. S1PR2 lies within the autosomal recessive nonsyndromic hearing impairment (ARNSHI) locus DFNB68 on 19p13.2. From exome sequence data we identified two pathogenic S1PR2 variants, c.323G>C (p.Arg108Pro) and c.419A>G (p.Tyr140Cys). Each of these variants co-segregates with congenital profound hearing impairment in consanguineous Pakistani families with maximum LOD scores of 6.4 for family DEM4154 and 3.3 for family PKDF1400. Neither S1PR2 missense variant was reported among ~120,000 chromosomes in the Exome Aggregation Consortium database, in 76 unrelated Pakistani exomes, or in 720 Pakistani control chromosomes. Both DNA variants affect highly conserved residues of S1PR2 and are predicted to be damaging by multiple bioinformatics tools. Molecular modeling predicts that these variants affect binding of sphingosine-1-phosphate (p.Arg108Pro) and G protein docking (p.Tyr140Cys). In the previously reported S1pr2(-/-) mice, stria vascularis abnormalities, organ of Corti degeneration, and profound hearing loss were observed. Additionally, hair cell defects were seen in both knockout mice and morphant zebrafish. Family PKDF1400 presents with ARNSHI, which is consistent with the lack of gross malformations in S1pr2(-/-) mice, whereas family DEM4154 has lower limb malformations in addition to hearing loss. Our findings suggest the possibility of developing therapies against hair cell damage (e.g., from ototoxic drugs) through targeted stimulation of S1PR2. PMID- 26805787 TI - Recent advances in co-amorphous drug formulations. AB - Co-amorphous drug delivery systems have recently gained considerable interest in the pharmaceutical field because of their potential to improve oral bioavailability of poorly water-soluble drugs through drug dissolution enhancement as a result of the amorphous nature of the material. A co-amorphous system is characterized by the use of only low molecular weight components that are mixed into a homogeneous single-phase co-amorphous blend. The use of only low molecular weight co-formers makes this approach very attractive, as the amount of amorphous stabilizer can be significantly reduced compared with other amorphous stabilization techniques. Because of this, several research groups started to investigate the co-amorphous formulation approach, resulting in an increasing amount of scientific publications over the last few years. This study provides an overview of the co-amorphous field and its recent findings. In particular, we investigate co-amorphous formulations from the viewpoint of solid dispersions, describe their formation and mechanism of stabilization, study their impact on dissolution and in vivo performance and briefly outline the future potentials. PMID- 26805789 TI - An Unusual Stress Metabolite from a Hydrothermal Vent Fungus Aspergillus sp. WU 243 Induced by Cobalt. AB - A novel hybrid polyketide-terpenoid, aspergstressin (1), possessing a unique fused polycyclic structure, was induced from culture broth of strain Aspergillus sp. WU 243 by cobalt ion stimulation. The strain was isolated from the digestive gland of Xenograpsus testudinatus, a unique type of crab which dwells in the Kueishantao hydrothermal vents off Taiwan. The chemical structure and relative configuration of the stress metabolite were established by spectroscopic means. Aspergillus sp. WU 243 produced aspergstressin (1) only under cobalt stressed culture conditions. The results show that stress-driven discovery of new natural products from hydrothermal vent fungi is an effective strategy to unveil the untapped reservoir of small molecules from species found in the hydrothermal vent environment. PMID- 26805790 TI - Biocompatible 3D Matrix with Antimicrobial Properties. AB - The aim of this study was to develop, characterize and assess the biological activity of a new regenerative 3D matrix with antimicrobial properties, based on collagen (COLL), hydroxyapatite (HAp), beta-cyclodextrin (beta-CD) and usnic acid (UA). The prepared 3D matrix was characterized by Scanning Electron Microscopy (SEM), Fourier Transform Infrared Microscopy (FT-IRM), Transmission Electron Microscopy (TEM), and X-ray Diffraction (XRD). In vitro qualitative and quantitative analyses performed on cultured diploid cells demonstrated that the 3D matrix is biocompatible, allowing the normal development and growth of MG-63 osteoblast-like cells and exhibited an antimicrobial effect, especially on the Staphylococcus aureus strain, explained by the particular higher inhibitory activity of usnic acid (UA) against Gram positive bacterial strains. Our data strongly recommend the obtained 3D matrix to be used as a successful alternative for the fabrication of three dimensional (3D) anti-infective regeneration matrix for bone tissue engineering. PMID- 26805788 TI - Imaging-guided delivery of RNAi for anticancer treatment. AB - The RNA interference (RNAi) technique is a new modality for cancer therapy, and several candidates are being tested clinically. In the development of RNAi-based therapeutics, imaging methods can provide a visible and quantitative way to investigate the therapeutic effect at anatomical, cellular, and molecular level; to noninvasively trace the distribution; to and study the biological processes in preclinical and clinical stages. Their abilities are important not only for therapeutic optimization and evaluation but also for shortening of the time of drug development to market. Typically, imaging-functionalized RNAi therapeutics delivery that combines nanovehicles and imaging techniques to study and improve their biodistribution and accumulation in tumor site has been progressively integrated into anticancer drug discovery and development processes. This review presents an overview of the current status of translating the RNAi cancer therapeutics in the clinic, a brief description of the biological barriers in drug delivery, and the roles of imaging in aspects of administration route, systemic circulation, and cellular barriers for the clinical translation of RNAi cancer therapeutics, and with partial content for discussing the safety concerns. Finally, we focus on imaging-guided delivery of RNAi therapeutics in preclinical development, including the basic principles of different imaging modalities, and their advantages and limitations for biological imaging. With growing number of RNAi therapeutics entering the clinic, various imaging methods will play an important role in facilitating the translation of RNAi cancer therapeutics from bench to bedside. PMID- 26805791 TI - Synthesis, Biological Evaluation and Molecular Docking of Certain Sulfones as Potential Nonazole Antifungal Agents. AB - We reported herein the synthesis, antifungal activity, docking and in silico ADME prediction studies of four novel series of sulfones 6a-f, 8a-c, 10a-f and 12a-c. All the newly synthesized sulfones were tested against four strains of Candida (including fluconazole-resistant Candida), two strains of Aspergillus, two dermatophytic fungi (Trichophytons mentagrophyte and Microsporum canis) and Syncephalastrum sp. with fluconazole as a reference drug. In general, compounds 8a and 10b showed selective and potent anticandidal activity (MIC: 0.19-0.81 uM) relative to fluconazole (MIC = 1.00 uM). Furthermore, 10e and 12a elicited a remarkable and selective antifungal activity against Aspergillus sp. and the dermatophytic fungi (MIC: 0.16-0.79 uM) relative to fluconazole (MIC: 2-2.6 uM). Moreover, the docking results of the sulfones 6a, 8a, 10a and 10b at the active site of CYT P450 14alpha-sterol demethylase showed a comparable binding interaction (interaction Energy = -34.87 to -42.43 kcal/mol) with that of fluconazole (IE = -40.37 kcal/mol). PMID- 26805792 TI - A Rapid Screening Analysis of Antioxidant Compounds in Native Australian Food Plants Using Multiplexed Detection with Active Flow Technology Columns. AB - Conventional techniques for identifying antioxidant and phenolic compounds in native Australian food plants are laborious and time-consuming. Here, we present a multiplexed detection technique that reduces analysis time without compromising separation performance. This technique is achieved using Active Flow Technology Parallel Segmented Flow (AFT-PSF) columns. Extracts from cinnamon myrtle (Backhousia myrtifolia) and lemon myrtle (Backhousia citriodora) leaves were analysed via multiplexed detection using an AFT-PSF column with underivatised UV VIS, mass spectroscopy (MS), and the 2,2-diphenyl-1-picrylhydrazyl (DPPH(*)) derivatisation for antioxidants as detection methods. A number of antioxidant compounds were detected in the extracts of each leaf extract. PMID- 26805793 TI - NHC Backbone Configuration in Ruthenium-Catalyzed Olefin Metathesis. AB - The catalytic properties of olefin metathesis ruthenium complexes bearing N heterocyclic carbene ligands with stereogenic centers on the backbone are described. Differences in catalytic behavior depending on the backbone configurations of symmetrical and unsymmetrical NHCs are discussed. In addition, an overview on asymmetric olefin metathesis promoted by chiral catalysts bearing C2-symmetric and C1-symmetric NHCs is provided. PMID- 26805794 TI - Skin Delivery and in Vitro Biological Evaluation of Trans-Resveratrol-Loaded Solid Lipid Nanoparticles for Skin Disorder Therapies. AB - The aim of this study was to evaluate the skin delivery and in vitro biological activity of trans-resveratrol (RES)-loaded solid lipid nanoparticles (SLNs). The SLNs were composed of stearic acid, poloxamer 407, soy phosphatidylcholine (SPC), an aqueous phase and 0.1% RES. The particle size, polydispersity index (PdI) and zeta potential were analyzed by dynamic light scattering (DLS). The SLNs were analyzed by scanning electron microscopy (SEM-FEG) and differential scanning calorimetry (DSC). In vitro RES-SLN skin permeation/retention assays were conducted, and their tyrosinase inhibitory activity was evaluated. An MTT reduction assay was performed on HaCat keratinocytes to determine in vitro cytotoxicity. The formulations had average diameter lower than 200 nm, the addition of SPC promoted increases in PdI in the RES-SLNs, but decreases PdI in the RES-free SLNs and the formulations exhibited zeta potentials smaller than -3 mV. The DSC analysis of the SLNs showed no endothermic peak attributable to RES. Microscopic analysis suggests that the materials formed had nanometric size distribution. Up to 45% of the RES permeated through the skin after 24 h. The RES loaded SLNs were more effective than kojic acid at inhibiting tyrosinase and proved to be non-toxic in HaCat keratinocytes. The results suggest that the investigated RES-loaded SLNs have potential use in skin disorder therapies. PMID- 26805795 TI - Synthesis, Spectroscopic, Structural and Quantum Chemical Studies of a New Imine Oxime and Its Palladium(II) Complex: Hydrolysis Mechanism. AB - In this work, we report synthesis, crystallographic, spectroscopic and quantum chemical studies of a new imine oxime, namely (4-nitro-phenyl)-(1-phenyl ethylimino)-acetaldehyde oxime (nppeieoH). Spectroscopic and X-ray diffraction studies showed that nppeieoH is hydrolyzed in aqueous solution, forming nitroisonitrosoacetophenone (ninap) and the hydrolysis product binds to Pd(II) to yield [Pd(nppeieo)(ninap)]. The mechanism of the hydrolysis reaction has been theoretically investigated in detail, using density functional theory (DFT) with the B3LYP method. The vibrational and the electronic spectra of nppeieoH and its Pd(II) complex, the HOMO and LUMO analysis, Mulliken atomic charges and molecular electrostatic potential were also performed. The predicted nonlinear optical properties of both compounds are higher than those of urea. PMID- 26805796 TI - On-Line Organic Solvent Field Enhanced Sample Injection in Capillary Zone Electrophoresis for Analysis of Quetiapine in Beagle Dog Plasma. AB - A rapid and sensitive capillary zone electrophoresis (CZE) method with field enhanced sample injection (FESI) was developed and validated for the determination of quetiapine fumarate in beagle dog plasma, with a sample pretreatment by LLE in 96-well deep format plate. The optimum separation was carried out in an uncoated 31.2 cm * 75 MUm fused-silica capillary with an applied voltage of 13 kV. The electrophoretic analysis was performed by 50 mM phosphate at pH 2.5. The detection wavelength was 210 nm. Under these optimized conditions, FESI with acetonitrile enhanced the sensitivity of quetiapine about 40-50 folds in total. The method was suitably validated with respect to stability, specificity, linearity, lower limit of quantitation, accuracy, precision and extraction recovery. Using mirtazapine as an internal standard (100 ng/mL), the response of quetiapine was linear over the range of 1-1000 ng/mL. The lower limit of quantification was 1 ng/mL. The intra- and inter-day precisions for the assay were within 4.8% and 12.7%, respectively. The method represents the first application of FESI-CZE to the analysis of quetiapine fumarate in beagle dog plasma after oral administration. PMID- 26805797 TI - Synthesis of Some Novel 2-Amino-5-arylazothiazole Disperse Dyes for Dyeing Polyester Fabrics and Their Antimicrobial Activity. AB - The present work describes the synthesis of a series of four novel biologically active 2-amino-5-arylazothiazole disperse dyes containing the sulfa drug nucleus. The structures of the synthesized thiazole derivatives are confirmed using UV spectrophotometry, infrared and nuclear magnetic resonance techniques and elemental analysis. The synthesized dyes are applied to polyester fabrics as disperse dyes and their fastness properties to washing, perspiration, rubbing, sublimation, and light are evaluated. The synthesized compounds exhibit promising biological efficiency against selected Gram-positive and Gram-negative pathogenic bacteria as well as fungi. PMID- 26805798 TI - Antiproliferative and Antioxidant Activities and Mycosporine-Like Amino Acid Profiles of Wild-Harvested and Cultivated Edible Canadian Marine Red Macroalgae. AB - Antiproliferative and antioxidant activities and mycosporine-like amino acid (MAA) profiles of methanol extracts from edible wild-harvested (Chondrus crispus, Mastocarpus stellatus, Palmaria palmata) and cultivated (C. crispus) marine red macroalgae were studied herein. Palythine, asterina-330, shinorine, palythinol, porphyra-334 and usujirene MAAs were identified in the macroalgal extracts by LC/MS/MS. Extract reducing activity rankings were (p < 0.001): wild P. palmata > cultivated C. crispus = wild M. stellatus > wild low-UV C. crispus > wild high-UV C. crispus; whereas oxygen radical absorbance capacities were (p < 0.001): wild M. stellatus > wild P. palmata > cultivated C. crispus > wild low-UV C. crispus > wild high-UV C. crispus. Extracts were antiproliferative against HeLa and U-937 cells (p < 0.001) from 0.125-4 mg/mL, 24 h. Wild P. palmata and cultivated C. crispus extracts increased (p < 0.001) HeLa caspase-3/7 activities and the proportion of cells arrested at Sub G1 (apoptotic) compared to wild-harvested C. crispus and M. stellatus extracts. HeLa cells incubated with wild P. palmata and cultivated C. crispus extracts also exhibited morphological changes characteristic of apoptosis (shrinkage, rounding). Thus, extracts rich in low polarity usujirene and polar palythine and asterina-330 MAAs were antiproliferative as inducers of apoptosis in HeLa cells. PMID- 26805799 TI - Cytotoxic Compounds from Juglans sinensis Dode Display Anti-Proliferative Activity by Inducing Apoptosis in Human Cancer Cells. AB - Phytochemical investigation of the bark of Juglans sinensis Dode (Juglandaceae) led to the isolation of two active compounds, 8-hydroxy-2-methoxy-1,4 naphthoquinone (1) and 5-hydroxy-2-methoxy-1,4-naphthoquinone (2), together with 15 known compounds 3-17. All compounds were isolated from this plant for the first time. The structures of 1 and 2 were elucidated by spectroscopic data analysis, including 1D and 2D NMR experiments. Compounds 1-17 were tested for their cytotoxicity against the A549 human lung cancer cell line; compounds 1 and 2 exhibited significant cytotoxicity and additionally had potent cytotoxicity against six human cancer cell lines, MCF7 (breast cancer), SNU423 (liver cancer), SH-SY5Y (neuroblastoma), HeLa (cervical cancer), HCT116 (colorectal cancer), and A549 (lung cancer). In particular, breast, colon, and lung cancer cells were more sensitive to the treatment using compound 1. In addition, compounds 1 and 2 showed strong cytotoxic activity towards human breast cancer cells MCF7, HS578T, and T47D, but not towards MCF10A normal-like breast cells. They also inhibited the colony formation of MCF7, A549, and HCT116 cells in a dose-dependent manner. Flow cytometry analysis revealed that the percentage of apoptotic cells significantly increased in MCF7 cells upon the treatment with compounds 1 and 2. The mechanism of cell death caused by compounds 1 and 2 may be attributed to the upregulation of Bax and downregulation of Bcl2. These findings suggest that compounds 1 and 2 may be regarded as potential therapeutic agents against cancer. PMID- 26805800 TI - Pharmacokinetics of Tyrosol Metabolites in Rats. AB - Tyrosol is considered a potential antioxidant; however, little is known regarding the pharmacokinetics of its metabolites. To study the pharmacokinetics of tyrosol derived metabolites after oral administration of a single dose of tyrosol, we attempted to identify tyrosol metabolites in rat plasma by using ultra performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Two tyrosol metabolites (M1 and M2) were detected in the plasma. M1 was identified as tyrosol-4-sulfate (T4S) with an [M - H](-) ion at m/z 217. While M2 showed an [M - H](-) ion at m/z 151.0, its metabolite was not identified. Pharmacokinetic analysis of T4S and M2 showed rapid uptake after oral administration of tyrosol within 1 h. The metabolites were rapidly distributed in most organs and tissues and eliminated within 4 h. The greatest T4S deposition by tissue weight was observed in the liver, followed by the kidney and spleen, while M2 was most concentrated in the kidney followed by the liver and spleen. These findings indicate that T4S and M2 were distributed mainly in tissues with an abundant blood supply and were rapidly excreted in urine. PMID- 26805802 TI - Serum Metabolomic Characterization of Liver Fibrosis in Rats and Anti-Fibrotic Effects of Yin-Chen-Hao-Tang. AB - Yin-Chen-Hao-Tang (YCHT) is a famous Chinese medicine formula which has long been used in clinical practice for treating various liver diseases, such as liver fibrosis. However, to date, the mechanism for its anti-fibrotic effects remains unclear. In this paper, an ultra-performance liquid chromatography-time-of-flight mass spectrometry (UPLC-TOF-MS)-based metabolomic study was performed to characterize dimethylnitrosamine (DMN)-induced liver fibrosis in rats and evaluate the therapeutic effects of YCHT. Partial least squares-discriminant analysis (PLS-DA) showed that the model group was well separated from the control group, whereas the YCHT-treated group exhibited a tendency to restore to the controls. Seven significantly changed fibrosis-related metabolites, including unsaturated fatty acids and lysophosphatidylcholines (Lyso-PCs), were identified. Moreover, statistical analysis demonstrated that YCHT treatment could reverse the levels of most metabolites close to the normal levels. These results, along with histological and biochemical examinations, indicate that YCHT has anti-fibrotic effects, which may be due to the suppression of oxidative stress and resulting lipid peroxidation involved in hepatic fibrogenesis. This study offers new opportunities to improve our understanding of liver fibrosis and the anti fibrotic mechanisms of YCHT. PMID- 26805803 TI - Quality Evaluation of Traditional Chinese Medicine Compounds in Xiaoyan Lidan Tablets: Fingerprint and Quantitative Analysis Using UPLC-MS. AB - XiaoyanLidan tablets (XYLDTs) are traditional Chinese medicines frequently used for syndromes of the liver and gallbladder, cholecystitis and cholangitis. To evaluate the consistency of the quality of commercial XYLDT preparations, we established a simple and reliable ultra-performance liquid chromatography (UPLC) method with a photodiode array (PDA) detector and mass spectrometry (MS), including a fingerprint analysis and quantification of the main pharmacologically active markers. In the UPLC-PDA detection-based fingerprint analysis of XYLDTs, approximately 39 peaks were found in the XYLDT chromatogram, 26 of which were attributed to Picrasmaquassioides, nine to Andrographis and four to Isodonserra. Subsequently, the structures of these bioactive markers were identified through ESI-MS analyses. Using the chemometricmethods of similarity analysis and principal component analysis, the five significant herbal componentswere determined as 4-methoxy-5-hydroxycanthin-6-one, andrographolide, dehydroandrographolide, neoandrographolide and rosmarinic acid, and these components were qualitatively assessed. Our experimental results demonstrated that combining the fingerprint analysis with UPLC-MS and multi-ingredient determination is useful for rapid pharmaceutical quality evaluation. Moreover, the combined approach can potentially differentiate the origin, determine the authenticity and assess the overall quality of the formulae. PMID- 26805801 TI - The Scavenging of DPPH, Galvinoxyl and ABTS Radicals by Imine Analogs of Resveratrol. AB - Resveratrol (3,5,4'-trihydroxystilbene) is a phytoalexin produced by plants. Resveratrol is known for its anti-cancer, antiviral and antioxidant properties. We prepared imine analogs of resveratrol ((hydroxyphenyliminomethyl)phenols) and tested their antioxidant activity. All prepared resveratrol analogs were able to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), galvinoxyl radical (GOR) and 2,2' azino-bis(3-ethylbenzothiazoline)-6-sulphonic acid (ABTS) radicals. The antioxidant activity efficiency correlated with the number and position of hydroxyl groups. The most effective antioxidants were resveratrol analogs containing three hydroxyl groups in the benzylidene part of their molecules. These results provide new insights into the relationship between the chemical structure and biological activity of resveratrol analogs. PMID- 26805804 TI - New alpha-Methylene-gamma-Butyrolactone Derivatives as Potential Fungicidal Agents: Design, Synthesis and Antifungal Activities. AB - In consideration of the fact that the alpha-methylene-gamma-butyrolactone moiety is a major bio-functional group in the structure of carabrone and possesses some agricultural biological activity, forty-six new ester and six new ether derivatives containing alpha-methylene-gamma-butyrolactone moieties were synthesized, and their fungicidal activities against Colletotrichum lagenarium and Botrytis cinerea were investigated. Most of the synthesized compounds showed moderate to significant fungicidal activity. Among them, halogen atom-containing derivatives showed better activity than others, especially compounds 6a,d which exhibited excellent fungicidal activity against C. lagenarium, with IC50 values of 7.68 and 8.17 MUM. The structure-activity relationship (SAR) analysis indicated that ester derivatives with electron-withdrawing groups on the benzene ring showed better fungicidal activity than those with electron-donating groups. A quantitative structure-activity relationship (QSAR) model (R2 = 0.9824, F = 203.01, S2 = 0.0083) was obtained through the heuristic method. The built model revealed a strong correlation of fungicidal activity against C. lagenarium with the molecular structures of these compounds. These results are expected to prove helpful in the design and exploration of low toxicity and high efficiency alpha methylene-gamma-butyrolactone-based fungicides. PMID- 26805805 TI - Recent Advances in the Emission and Functions of Plant Vegetative Volatiles. AB - Plants synthesize and emit a large variety of volatile organic compounds, which possess extremely important ecological functions. In most case, most plant volatiles are liquids, rather than gases, at room temperature. Some volatiles are emitted "on demand" when plants, especially vegetative parts, are exposed to abiotic or biotic stress. In this review, we summarize some of the highlights of plant vegetative volatile emission and functions research published during the past few years. PMID- 26805806 TI - Graveoline Analogs Exhibiting Selective Acetylcholinesterase Inhibitory Activity as Potential Lead Compounds for the Treatment of Alzheimer's Disease. AB - This study designed and synthesized a series of new graveoline analogs on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of these analogs was also evaluated. Results showed that the synthesized graveoline analogs displayed stronger inhibitory activity against AChE and higher selectivity than butyrylcholine esterase (BuChE) (Selectivity Index from 45 to 486). When the two sites in the graveoline parent ring substituting phenyl and amino terminal had six chemical bonds (n = 3) and the terminal amino was piperidine, compound 5c showed the best activity. Furthermore, the mechanism of action and binding mode were explored by enzyme kinetic simulation, molecular docking, and thioflavin T-based fluorometric assay. Cytotoxicity assay showed that the low concentration of the analogs did not affect the viability of the neurocyte SH-SY5Y. PMID- 26805807 TI - Protective Effect of Cleistocalyx nervosum var. paniala Fruit Extract against Oxidative Renal Damage Caused by Cadmium. AB - Cadmium nephrotoxicity is a serious environmental health problem as it will eventually end up with end stage renal disease. The pathobiochemical mechanism of this toxic heavy metal is related to oxidative stress. This study investigated whether Cleistocalyx nervosum var. paniala fruit extract (CNFE) could protect the kidney against oxidative injury caused by cadmium. Initial analysis of the extract revealed antioxidant abilities and high levels of polyphenols, particularly catechin. Its potential renal benefits was further explored in rats treated with vehicle, CNFE, cadmium (2 mg/kg), and cadmium plus CNFE (0.5, 1, 2 g/kg) for four weeks. Oxidative renal injury was developed after cadmium exposure as evidenced by blood urea nitrogen and creatinine retention, glomerular filtration reduction, renal structural damage, together with increased nitric oxide and malondialdehyde, but decreased antioxidant thiols, superoxide dismutase, and catalase in renal tissues. Cadmium-induced nephrotoxicity was diminished in rats supplemented with CNFE, particularly at the doses of 1 and 2 g/kg. It is concluded that CNFE is able to protect against the progression of cadmium nephrotoxicity, mostly via its antioxidant power. The results also point towards a promising role for this naturally-occurring antioxidant to combat other human disorders elicited by disruption of redox homeostasis. PMID- 26805808 TI - The Blood-Brain Barrier Permeability of Lignans and Malabaricones from the Seeds of Myristica fragrans in the MDCK-pHaMDR Cell Monolayer Model. AB - The blood-brain barrier (BBB) permeability of twelve lignans and three phenolic malabaricones from the seeds of Myristica fragrans (nutmeg) were studied with the MDCK-pHaMDR cell monolayer model. The samples were measured by high-performance liquid chromatography and the apparent permeability coefficients (Papp) were calculated. Among the fifteen test compounds, benzonfuran-type, dibenzylbutane type and arylnaphthalene-type lignans showed poor to moderate permeabilities with Papp values at 10(-8)-10(-6) cm/s; those of 8-O-4'-neolignan and tetrahydrofuran lignan were at 10(-6)-10(-5) cm/s, meaning that their permeabilities are moderate to high; the permeabilities of malabaricones were poor as their Papp values were at 10(-8)-10(-7) cm/s. To 5-methoxy-dehydrodiisoeugenol (2), erythro-2-(4-allyl 2,6-dimethoxyphenoxy)-1-(3,4-dimethoxyphenyl)-propan-1-ol acetate (6), verrucosin (8), and nectandrin B (9), an efflux way was involved and the main transporter for 6, 8 and 9 was demonstrated to be P-glycoprotein. The time and concentration dependency experiments indicated the main transport mechanism for neolignans dehydrodiisoeugenol (1), myrislignan (7) and 8 was passive diffusion. This study summarized the relationship between the BBB permeability and structure parameters of the test compounds, which could be used to preliminarily predict the transport of a compound through BBB. The results provide a significant molecular basis for better understanding the potential central nervous system effects of nutmeg. PMID- 26805809 TI - The Inhibitory Mechanisms Study of 5,6,4'-Trihydroxy-7,3'-Dimethoxyflavone against the LPS-Induced Macrophage Inflammatory Responses through the Antioxidant Ability. AB - The whole plant of Anisomeles ovata has been widely used in Taiwan for treating inflammation-related skin and liver diseases, however, the detailed pharmacology mechanisms have yet to be elucidated. In the present study, one of the major components, 5,6,4'-trihydroxy-7,3'-dimethoxyflavone (5-TDMF), was purified from a methanol extract of Anisomeles ovata. A pharmacological study of this compound suggests that 5-TDMF possesses potent free radical scavenging activity both in vitro and ex vivo. Furthermore, 5-TDMF reduces nitric oxide and pro-inflammatory cytokine production in LPC-treated RAW 264.7 cells through the attenuation of nitric oxide synthase and cyclooxygenase-2. Additional experiments suggest that of 5-TDMF interferes with nuclear factor-kappaB translocation and mitogen activated protein kinase pathways. These results identify 5-TDMF as an anti oxidant and anti-inflammatory compound, explain the pharmacologic function of Anisomeles ovata and suggest its great potential as a new anti-inflammatory remedy. PMID- 26805810 TI - Antiproliferative Effects of New Dimeric Ellagitannin from Cornus alba in Prostate Cancer Cells Including Apoptosis-Related S-Phase Arrest. AB - Activity-guided isolation of 80% acetone extract of Cornus alba, which is traditionally used as an anti-inflammatory, hemostatic and diuretic in Korea, yielded one novel compound, tentatively designated cornusiin H (13), together with 12 known compounds. The known compounds included four flavonoids (catechin (1), quercetin-3-O-beta-D-glucuronide (2), quercetin-3-O-beta-D-glucopyranoside (3), kaempferol-3-O-beta-D-glucopyranoside (4)) and eight hydrolysable tannins (gallic acid (5), 2,6-di-O-galloyl-hamamelofuranoside (6), 2-galloyl-4-caffeoyl-L threonic acid (7) 2,3-di-O-galloyl-4-caffeoyl-L-threonic acid (8), 1,2,3,4,6 penta-O-galloyl-beta-D-glucopyranoside (9), cornusiin B (10), cornusiin A (11) and camptothin B (12)). All compounds exhibited potent 1,1-diphenyl-2 picrylhydrazyl (DPPH)-free radical scavenging activity. Especially, the radical scavenging activities of 6 and 9-13 were higher than that of vitamin C. Compounds 9, 11, 12 and 13 inhibited the production of nitric oxide (NO) in lipopolysaccharide-stimulated RAW264.7 cells to the same degree as N(G) Monomethyl-L-arginine (L-NMMA). When the antiproliferative effects of the isolated compounds were assessed in prostate cancer cells, the dimeric ellagitannins (11-13) selectively inhibited LNCaP hormone-dependent prostate cancer cells. Flow cytometry analysis indicated that the dimeric ellagitannins induced apoptosis and S-phase arrest. These results suggest that dimeric ellagitannins from Cornus alba can be developed as functional materials or herbal medicines for prostate tumors such as benign prostate hyperplasia and early-stage prostate cancer. PMID- 26805811 TI - Coumarins as Potential Antioxidant Agents Complemented with Suggested Mechanisms and Approved by Molecular Modeling Studies. AB - Syntheses of coumarins, which are a structurally interesting antioxidant activity, was done in this article. The modification of 7-hydroxycoumarin by different reaction steps was done to yield target compounds. Molecular structures were characterized by different spectroscopical techniques (Fourier transformation infrared and nuclear magnetic resonance). Antioxidant activities were performed by using various in vitro spectrophometric assays against 1,1 diphenyl-2-picrylhydrazyl (DPPH) radical and hydrogen peroxide (H2O2). All compounds exhibited high efficiency as antioxidants compared to ascorbic acid. The highest efficiency scavenging activity was found for compound 3 (91.0 +/- 5.0), followed by compounds 2 and 4 (88.0 +/- 2.00; and 87.0 +/- 3.00). Ascorbic acid C was used as a standard drug with a percentage inhibition of 91.00 +/- 1.5. The mechanism of the synthesized compounds as antioxidants was also studied. Hartree-Fock-based quantum chemical studies have been carried out with the basis set to 3-21G, in order to obtain information about the three-dimensional (3D) geometries, electronic structure, molecular modeling, and electronic levels, namely HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital), to understand the antioxidant activity for the synthesized compounds. PMID- 26805812 TI - Antioxidant Activity of 3-[N-(Acylhydrazono)ethyl]-4-hydroxy-coumarins. AB - A series of 3-acylhydrazono-4-hydroxycoumarins were synthesized via condensation of 3-acetyl-4-hydroxycoumarin with appropriate hydrazides. The structures of the newly-synthesized compounds were characterized by spectral and elememental analysis or HRMS measurements. Their antioxidant properties were evaluated by using scavenging effects on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical as well as inhibition of lipid peroxidation. Moreover, their ability to inhibit in vitro soybean lipoxygenase has been investigated. They were found to be capable of rapid inactivation of alkylperoxy radicals. PMID- 26805813 TI - Iron Homeostasis in Health and Disease. AB - Iron is required for the survival of most organisms, including bacteria, plants, and humans. Its homeostasis in mammals must be fine-tuned to avoid iron deficiency with a reduced oxygen transport and diminished activity of Fe dependent enzymes, and also iron excess that may catalyze the formation of highly reactive hydroxyl radicals, oxidative stress, and programmed cell death. The advance in understanding the main players and mechanisms involved in iron regulation significantly improved since the discovery of genes responsible for hemochromatosis, the IRE/IRPs machinery, and the hepcidin-ferroportin axis. This review provides an update on the molecular mechanisms regulating cellular and systemic Fe homeostasis and their roles in pathophysiologic conditions that involve alterations of iron metabolism, and provides novel therapeutic strategies to prevent the deleterious effect of its deficiency/overload. PMID- 26805814 TI - VLDL from Metabolic Syndrome Individuals Enhanced Lipid Accumulation in Atria with Association of Susceptibility to Atrial Fibrillation. AB - Metabolic syndrome (MetS) represents a cluster of metabolic derangements. Dyslipidemia is an important factor in MetS and is related to atrial fibrillation (AF). We hypothesized that very low density lipoproteins (VLDL) in MetS (MetS VLDL) may induce atrial dilatation and vulnerability to AF. VLDL was therefore separated from normal (normal-VLDL) and MetS individuals. Wild type C57BL/6 male mice were divided into control, normal-VLDL (nVLDL), and MetS-VLDL (msVLDL) groups. VLDL (15 ug/g) and equivalent volumes of saline were injected via tail vein three times a week for six consecutive weeks. Cardiac chamber size and function were measured by echocardiography. MetS-VLDL significantly caused left atrial dilation (control, n = 10, 1.64 +/- 0.23 mm; nVLDL, n = 7, 1.84 +/- 0.13 mm; msVLDL, n = 10, 2.18 +/- 0.24 mm; p < 0.0001) at week 6, associated with decreased ejection fraction (control, n = 10, 62.5% +/- 7.7%, vs. msVLDL, n = 10, 52.9% +/- 9.6%; p < 0.05). Isoproterenol-challenge experiment resulted in AF in young msVLDL mice. Unprovoked AF occurred only in elderly msVLDL mice. Immunohistochemistry showed excess lipid accumulation and apoptosis in msVLDL mice atria. These findings suggest a pivotal role of VLDL in AF pathogenesis for MetS individuals. PMID- 26805816 TI - Unraveling Molecular Differences of Gastric Cancer by Label-Free Quantitative Proteomics Analysis. AB - Gastric cancer (GC) has significant morbidity and mortality worldwide and especially in China. Its molecular pathogenesis has not been thoroughly elaborated. The acknowledged biomarkers for diagnosis, prognosis, recurrence monitoring and treatment are lacking. Proteins from matched pairs of human GC and adjacent tissues were analyzed by a coupled label-free Mass Spectrometry (MS) approach, followed by functional annotation with software analysis. Nano-LC MS/MS, quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry were used to validate dysregulated proteins. One hundred forty-six dysregulated proteins with more than twofold expressions were quantified, 22 of which were first reported to be relevant with GC. Most of them were involved in cancers and gastrointestinal disease. The expression of a panel of four upregulated nucleic acid binding proteins, heterogeneous nuclear ribonucleoprotein hnRNPA2B1, hnRNPD, hnRNPL and Y-box binding protein 1 (YBX-1) were validated by Nano-LC-MS/MS, qRT-PCR, western blot and immunohistochemistry assays in ten GC patients' tissues. They were located in the keynotes of a predicted interaction network and might play important roles in abnormal cell growth. The label-free quantitative proteomic approach provides a deeper understanding and novel insight into GC-related molecular changes and possible mechanisms. It also provides some potential biomarkers for clinical diagnosis. PMID- 26805817 TI - The Clinical Significance of Phosphorylated Heat Shock Protein 27 (HSPB1) in Pancreatic Cancer. AB - Pancreatic cancer is one of most aggressive forms of cancer. After clinical detection it exhibits fast metastatic growth. Heat shock protein 27 (HSP27; HSPB1) has been characterized as a molecular chaperone which modifies the structures and functions of other proteins in cells when they are exposed to various stresses, such as chemotherapy. While the administration of gemcitabine, an anti-tumor drug, has been the standard treatment for patients with advanced pancreatic cancer, accumulating evidence shows that HSP27 plays a key role in the chemosensitivity to gemcitabine. In addition, phosphorylated HSP27 induced by gemcitabine has been associated with the inhibition of pancreatic cancer cell growth. In this review, we summarize the role of phosphorylated HSP27, as well as HSP27, in the regulation of chemosensitivity in pancreatic cancer. PMID- 26805815 TI - Structure Prediction: New Insights into Decrypting Long Noncoding RNAs. AB - Long noncoding RNAs (lncRNAs), which form a diverse class of RNAs, remain the least understood type of noncoding RNAs in terms of their nature and identification. Emerging evidence has revealed that a small number of newly discovered lncRNAs perform important and complex biological functions such as dosage compensation, chromatin regulation, genomic imprinting, and nuclear organization. However, understanding the wide range of functions of lncRNAs related to various processes of cellular networks remains a great experimental challenge. Structural versatility is critical for RNAs to perform various functions and provides new insights into probing the functions of lncRNAs. In recent years, the computational method of RNA structure prediction has been developed to analyze the structure of lncRNAs. This novel methodology has provided basic but indispensable information for the rapid, large-scale and in depth research of lncRNAs. This review focuses on mainstream RNA structure prediction methods at the secondary and tertiary levels to offer an additional approach to investigating the functions of lncRNAs. PMID- 26805818 TI - Photodynamic Therapy in Non-Gastrointestinal Thoracic Malignancies. AB - Photodynamic therapy has a role in the management of early and late thoracic malignancies. It can be used to facilitate minimally-invasive treatment of early endobronchial tumours and also to palliate obstructive and bleeding effects of advanced endobronchial tumours. Photodynamic therapy has been used as a means of downsizing tumours to allow for resection, as well as reducing the extent of resection necessary. It has also been used successfully for minimally-invasive management of local recurrences, which is especially valuable for patients who are not eligible for radiation therapy. Photodynamic therapy has also shown promising results in mesothelioma and pleural-based metastatic disease. As new generation photosensitizers are being developed and tested and methodological issues continue to be addressed, the role of photodynamic therapy in thoracic malignancies continues to evolve. PMID- 26805819 TI - Column Selection for Biomedical Analysis Supported by Column Classification Based on Four Test Parameters. AB - This article focuses on correlating the column classification obtained from the method created at the Katholieke Universiteit Leuven (KUL), with the chromatographic resolution attained in biomedical separation. In the KUL system, each column is described with four parameters, which enables estimation of the FKUL value characterising similarity of those parameters to the selected reference stationary phase. Thus, a ranking list based on the FKUL value can be calculated for the chosen reference column, then correlated with the results of the column performance test. In this study, the column performance test was based on analysis of moclobemide and its two metabolites in human plasma by liquid chromatography (LC), using 18 columns. The comparative study was performed using traditional correlation of the FKUL values with the retention parameters of the analytes describing the column performance test. In order to deepen the comparative assessment of both data sets, factor analysis (FA) was also used. The obtained results indicated that the stationary phase classes, closely related according to the KUL method, yielded comparable separation for the target substances. Therefore, the column ranking system based on the FKUL-values could be considered supportive in the choice of the appropriate column for biomedical analysis. PMID- 26805820 TI - The TEAD Family and Its Oncogenic Role in Promoting Tumorigenesis. AB - The TEAD family of transcription factors is necessary for developmental processes. The family members contain a TEA domain for the binding with DNA elements and a transactivation domain for the interaction with transcription coactivators. TEAD proteins are required for the participation of coactivators to transmit the signal of pathways for the downstream signaling processes. TEADs also play an important role in tumor initiation and facilitate cancer progression via activating a series of progression-inducing genes, such as CTGF, Cyr61, Myc and Gli2. Recent studies have highlighted that TEADs, together with their coactivators, promote or even act as the crucial parts in the development of various malignancies, such as liver, ovarian, breast and prostate cancers. Furthermore, TEADs are proposed to be useful prognostic biomarkers due to the ideal correlation between high expression and clinicopathological parameters in gastric, breast, ovarian and prostate cancers. In this review, we summarize the functional role of TEAD proteins in tumorigenesis and discuss the key role of TEAD transcription factors in the linking of signal cascade transductions. Improved knowledge of the TEAD proteins will be helpful for deep understanding of the molecular mechanisms of tumorigenesis and identifying ideal predictive or prognostic biomarkers, even providing clinical translation for anticancer therapy in human cancers. PMID- 26805821 TI - Elucidating the Diversity of Aquatic Microdochium and Trichoderma Species and Their Activity against the Fish Pathogen Saprolegnia diclina. AB - Animals and plants are increasingly threatened by emerging fungal and oomycete diseases. Amongst oomycetes, Saprolegnia species cause population declines in aquatic animals, especially fish and amphibians, resulting in significant perturbation in biodiversity, ecological balance and food security. Due to the prohibition of several chemical control agents, novel sustainable measures are required to control Saprolegnia infections in aquaculture. Previously, fungal community analysis by terminal restriction fragment length polymorphism (T-RFLP) revealed that the Ascomycota, specifically the genus Microdochium, was an abundant fungal phylum associated with salmon eggs from a commercial fish farm. Here, phylogenetic analyses showed that most fungal isolates obtained from salmon eggs were closely related to Microdochium lycopodinum/Microdochium phragmitis and Trichoderma viride species. Phylogenetic and quantitative PCR analyses showed both a quantitative and qualitative difference in Trichoderma population between diseased and healthy salmon eggs, which was not the case for the Microdochium population. In vitro antagonistic activity of the fungi against Saprolegnia diclina was isolate-dependent; for most Trichoderma isolates, the typical mycoparasitic coiling around and/or formation of papilla-like structures on S. diclina hyphae were observed. These results suggest that among the fungal community associated with salmon eggs, Trichoderma species may play a role in Saprolegnia suppression in aquaculture. PMID- 26805822 TI - An Overview of Direct Somatic Reprogramming: The Ins and Outs of iPSCs. AB - Stem cells are classified into embryonic stem cells and adult stem cells. An evolving alternative to conventional stem cell therapies is induced pluripotent stem cells (iPSCs), which have a multi-lineage potential comparable to conventionally acquired embryonic stem cells with the additional benefits of being less immunoreactive and avoiding many of the ethical concerns raised with the use of embryonic material. The ability to generate iPSCs from somatic cells provides tremendous promise for regenerative medicine. The breakthrough of iPSCs has raised the possibility that patient-specific iPSCs can provide autologous cells for cell therapy without the concern for immune rejection. iPSCs are also relevant tools for modeling human diseases and drugs screening. However, there are still several hurdles to overcome before iPSCs can be used for translational purposes. Here, we review the recent advances in somatic reprogramming and the challenges that must be overcome to move this strategy closer to clinical application. PMID- 26805824 TI - Cell Therapy Using Bone Marrow-Derived Stem Cell Overexpressing BMP-7 for Degenerative Discs in a Rat Tail Disc Model. AB - Degenerative discs can cause low back pain. Cell-based transplantation or growth factors therapy have been suggested as a strategy to stimulate disc regeneration. Bone marrow-derived mesenchymal stem cells (BMDMSC) containing bone morphogenetic protein-7 (BMP-7) gene were constructed. We evaluated the effectiveness of these BMP-7 overexpressing cells on degenerative discs in rat tails. In vitro and in vivo studies were designed. In the first stage, the rats were divided into two group according to discs punctured by different needle gauges (18 gauge and 22 gauge). In the second stage, the ideal size of needle was used to induce rat tail disc degeneration. These animals are divided into three groups according to timing of treatment (zero-week, two-week, four-week). Each group was divided into three treating subgroups: control group, BMDMSC group, and Baculo-BMP-7-BMDMSC group. Each rat undergoes radiography examination every two weeks. After eight weeks, the discs were histologically examined with hematoxylin and eosin stain and Alcian blue stain. The 18-gauge group exhibited significant decrease in disc height index (%) than 22-gauge group at eight weeks at both Co6-7 (58.1% +/- 2.8% vs. 63.7% +/- 1.0%, p = 0.020) and Co8-9 discs (62.7% +/- 2.8% vs. 62.8% +/- 1.5%, p = 0.010). Baculo-BMP-7-BMDMSCs group showed significant difference in disc height index compared to the BMDMSCs group at both Co6-7 (93.7% +/- 1.5% vs. 84.8% +/- 1.0%, p = 0.011) and Co8-9 (86.0% +/- 2.1% vs. 81.8% +/- 1.7%, p = 0.012). In Baculo-BMP-7-BMDMSCs group, the zero-week treatment subgroup showed significant better in disc height index compared to two-week treatment group (p = 0.044), and four-week treatment group (p = 0.011). The zero-week treatment subgroup in Baculo-BMP-7-BMDMSCs group also had significant lower histology score than two-week treatment (4.3 vs. 5.7, p = 0.045) and four-week treatment (4.3 vs. 6.0, p = 0.031). In conclusion, Baculo-BMP-7-BMDMSC can slow down the progression of disc degeneration, but could not provide evidence of regeneration. Early treatment might obtain more distinct results. PMID- 26805825 TI - Biodegradable Polymers Influence the Effect of Atorvastatin on Human Coronary Artery Cells. AB - Drug-eluting stents (DES) have reduced in-stent-restenosis drastically. Yet, the stent surface material directly interacts with cascades of biological processes leading to an activation of cellular defense mechanisms. To prevent adverse clinical implications, to date almost every patient with a coronary artery disease is treated with statins. Besides their clinical benefit, statins exert a number of pleiotropic effects on endothelial cells (ECs). Since maintenance of EC function and reduction of uncontrolled smooth muscle cell (SMC) proliferation represents a challenge for new generation DES, we investigated the effect of atorvastatin (ATOR) on human coronary artery cells grown on biodegradable polymers. Our results show a cell type-dependent effect of ATOR on ECs and SMCs. We observed polymer-dependent changes in IC50 values and an altered ATOR-uptake leading to an attenuation of statin-mediated effects on SMC growth. We conclude that the selected biodegradable polymers negatively influence the anti proliferative effect of ATOR on SMCs. Hence, the process of developing new polymers for DES coating should involve the characterization of material-related changes in mechanisms of drug actions. PMID- 26805826 TI - Metformin Prevents Renal Fibrosis in Mice with Unilateral Ureteral Obstruction and Inhibits Ang II-Induced ECM Production in Renal Fibroblasts. AB - Renal fibrosis is the final common pathway of chronic kidney disease (CKD), and no effective medication is available clinically for managing its progression. Metformin was initially developed as an anti-diabetic drug and recently gained attention for its potential in the treatment of other diseases. In this study, we investigated its effects on renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO) in vivo and in angiotensin II (Ang II)-treated renal fibroblast NRK-49F cells in vitro. Our data showed that UUO induced renal fibrosis and combined with the activation of ERK signaling, the upregulation of fibronectin, collagen I, and transforming growth factor-beta (TGF-beta). The administration of metformin inhibited the activation of ERK signaling and attenuated the production of extracellular matrix (ECM) proteins and collagen deposition in the obstructed kidneys. In cultured renal fibroblasts, Ang II increased the expression of fibronectin and collagen I and also activated ERK signaling and TGF-beta in a time-dependent manner. Pretreatment of the cells with metformin blocked Ang II-induced ERK signaling activation and ECM overproduction. Our results show that metformin prevents renal fibrosis, possibly through the inhibition of ERK signaling, and may be a novel strategy for the treatment of renal fibrosis. PMID- 26805823 TI - Cadmium Protection Strategies--A Hidden Trade-Off? AB - Cadmium (Cd) is a non-essential transition metal which is introduced into the biosphere by various anthropogenic activities. Environmental pollution with Cd poses a major health risk and Cd toxicity has been extensively researched over the past decades. This review aims at changing the perspective by discussing protection mechanisms available to counteract a Cd insult. Antioxidants, induction of antioxidant enzymes, and complexation of Cd to glutathione (GSH) and metallothionein (MT) are the most potent protective measures to cope with Cd induced oxidative stress. Furthermore, protection mechanisms include prevention of endoplasmic reticulum (ER) stress, mitophagy and metabolic stress, as well as expression of chaperones. Pre-exposure to Cd itself, or co-exposure to other metals or trace elements can improve viability under Cd exposure and cells have means to reduce Cd uptake and improve Cd removal. Finally, environmental factors have negative or positive effects on Cd toxicity. Most protection mechanisms aim at preventing cellular damage. However, this might not be possible without trade offs like an increased risk of carcinogenesis. PMID- 26805828 TI - A Microwave Ring-Resonator Sensor for Non-Invasive Assessment of Meat Aging. AB - The assessment of moisture loss from meat during the aging period is a critical issue for the meat industry. In this article, a non-invasive microwave ring resonator sensor is presented to evaluate the moisture content, or more precisely water holding capacity (WHC) of broiler meat over a four-week period. The developed sensor has shown significant changes in its resonance frequency and return loss due to reduction in WHC in the studied duration. The obtained results are also confirmed by physical measurements. Further, these results are evaluated using the Fricke model, which provides a good fit for electric circuit components in biological tissue. Significant changes were observed in membrane integrity, where the corresponding capacitance decreases 30% in the early aging (0D-7D) period. Similarly, the losses associated with intracellular and extracellular fluids exhibit changed up to 42% and 53%, respectively. Ultimately, empirical polynomial models are developed to predict the electrical component values for a better understanding of aging effects. The measured and calculated values are found to be in good agreement. PMID- 26805827 TI - Cissus sicyoides: Pharmacological Mechanisms Involved in the Anti-Inflammatory and Antidiarrheal Activities. AB - The objective of this study was to evaluate the pharmacological mechanisms involved in anti-inflammatory and antidiarrheal actions of hydroalcoholic extract obtained from the leaves of Cissus sicyoides (HECS). The anti-inflammatory effect was evaluated by oral administration of HECS against acute model of edema induced by xylene, and the mechanisms of action were analysed by involvement of arachidonic acid (AA) and prostaglandin E2 (PGE2). The antidiarrheal effect of HECS was observed and we analyzed the motility and accumulation of intestinal fluid. We also analyzed the antidiarrheal mechanisms of action of HECS by evaluating the role of the opioid receptor, alpha2 adrenergic receptor, muscarinic receptor, nitric oxide (NO) and PGE2. The oral administration of HECS inhibited the edema induced by xylene and AA and was also able to significantly decrease the levels of PGE2. The extract also exhibited significant anti diarrheal activity by reducing motility and intestinal fluid accumulation. This extract significantly reduced intestinal transit stimulated by muscarinic agonist and intestinal secretion induced by PGE2. Our data demonstrate that the mechanism of action involved in the anti-inflammatory effect of HECS is related to PGE2. The antidiarrheal effect of this extract may be mediated by inhibition of contraction by acting on the intestinal smooth muscle and/or intestinal transit. PMID- 26805829 TI - Construction of an Electrochemical Sensor Based on Carbon Nanotubes/Gold Nanoparticles for Trace Determination of Amoxicillin in Bovine Milk. AB - In this work, a novel electrochemical sensor was fabricated for determination of amoxicillin in bovine milk samples by decoration of carboxylated multi-walled carbon nanotubes (MWCNTs) with gold nanoparticles (AuNPs) using ethylenediamine (en) as a cross linker (AuNPs/en-MWCNTs). The constructed nanocomposite was homogenized in dimethylformamide and drop casted on screen printed electrode. Field emission scanning electron microscopy (FESEM), energy dispersive X-Ray (EDX), X-Ray diffraction (XRD) and cyclic voltammetry were used to characterize the synthesized nanocomposites. The results show that the synthesized nanocomposites induced a remarkable synergetic effect for the oxidation of amoxicillin. Effect of some parameters, including pH, buffer, scan rate, accumulation potential, accumulation time and amount of casted nanocomposites, on the sensitivity of fabricated sensor were optimized. Under the optimum conditions, there was two linear calibration ranges from 0.2-10 uM and 10-30 uM with equations of Ipa (uA) = 2.88C (uM) + 1.2017; r = 0.9939 and Ipa (uA) = 0.88C (uM) + 22.97; r = 0.9973, respectively. The limit of detection (LOD) and limit of quantitation (LOQ) were calculated as 0.015 uM and 0.149 uM, respectively. The fabricated electrochemical sensor was successfully applied for determination of Amoxicillin in bovine milk samples and all results compared with high performance liquid chromatography (HPLC) standard method. PMID- 26805830 TI - DC-Compensated Current Transformer. AB - Instrument current transformers (CTs) measure AC currents. The DC component in the measured current can saturate the transformer and cause gross error. We use fluxgate detection and digital feedback compensation of the DC flux to suppress the overall error to 0.15%. This concept can be used not only for high-end CTs with a nanocrystalline core, but it also works for low-cost CTs with FeSi cores. The method described here allows simultaneous measurements of the DC current component. PMID- 26805831 TI - Analysis of BeiDou Satellite Measurements with Code Multipath and Geometry-Free Ionosphere-Free Combinations. AB - Using GNSS observable from some stations in the Asia-Pacific area, the carrier-to noise ratio (CNR) and multipath combinations of BeiDou Navigation Satellite System (BDS), as well as their variations with time and/or elevation were investigated and compared with those of GPS and Galileo. Provided the same elevation, the CNR of B1 observables is the lowest among the three BDS frequencies, while B3 is the highest. The code multipath combinations of BDS inclined geosynchronous orbit (IGSO) and medium Earth orbit (MEO) satellites are remarkably correlated with elevation, and the systematic "V" shape trends could be eliminated through between-station-differencing or modeling correction. Daily periodicity was found in the geometry-free ionosphere-free (GFIF) combinations of both BDS geostationary Earth orbit (GEO) and IGSO satellites. The variation range of carrier phase GFIF combinations of GEO satellites is -2.0 to 2.0 cm. The periodicity of carrier phase GFIF combination could be significantly mitigated through between-station differencing. Carrier phase GFIF combinations of BDS GEO and IGSO satellites might also contain delays related to satellites. Cross correlation suggests that the GFIF combinations' time series of some GEO satellites might vary according to their relative geometries with the sun. PMID- 26805832 TI - Realtime Gas Emission Monitoring at Hazardous Sites Using a Distributed Point Source Sensing Infrastructure. AB - This paper describes a distributed point-source monitoring platform for gas level and leakage detection in hazardous environments. The platform, based on a wireless sensor network (WSN) architecture, is organised into sub-networks to be positioned in the plant's critical areas; each sub-net includes a gateway unit wirelessly connected to the WSN nodes, hence providing an easily deployable, stand-alone infrastructure featuring a high degree of scalability and reconfigurability. Furthermore, the system provides automated calibration routines which can be accomplished by non-specialized maintenance operators without system reliability reduction issues. Internet connectivity is provided via TCP/IP over GPRS (Internet standard protocols over mobile networks) gateways at a one-minute sampling rate. Environmental and process data are forwarded to a remote server and made available to authenticated users through a user interface that provides data rendering in various formats and multi-sensor data fusion. The platform is able to provide real-time plant management with an effective; accurate tool for immediate warning in case of critical events. PMID- 26805833 TI - Closed-Loop Control of Chemical Injection Rate for a Direct Nozzle Injection System. AB - To realize site-specific and variable-rate application of agricultural pesticides, accurately metering and controlling the chemical injection rate is necessary. This study presents a prototype of a direct nozzle injection system (DNIS) by which chemical concentration transport lag was greatly reduced. In this system, a rapid-reacting solenoid valve (RRV) was utilized for injecting chemicals, driven by a pulse-width modulation (PWM) signal at 100 Hz, so with varying pulse width the chemical injection rate could be adjusted. Meanwhile, a closed-loop control strategy, proportional-integral-derivative (PID) method, was applied for metering and stabilizing the chemical injection rate. In order to measure chemical flow rates and input them into the controller as a feedback in real-time, a thermodynamic flowmeter that was independent of chemical viscosity was used. Laboratory tests were conducted to assess the performance of DNIS and PID control strategy. Due to the nonlinear input-output characteristics of the RRV, a two-phase PID control process obtained better effects as compared with single PID control strategy. Test results also indicated that the set-point chemical flow rate could be achieved within less than 4 s, and the output stability was improved compared to the case without control strategy. PMID- 26805834 TI - Assessment of Three Tropospheric Delay Models (IGGtrop, EGNOS and UNB3m) Based on Precise Point Positioning in the Chinese Region. AB - Tropospheric delays are one of the main sources of errors in the Global Navigation Satellite System (GNSS). They are usually corrected by using tropospheric delay models, which makes the accuracy of the models rather critical for accurate positioning. To provide references for suitable models to be chosen for GNSS users in China, we conduct herein a comprehensive study of the performances of the IGGtrop, EGNOS and UNB3m models in China. Firstly, we assess the models using 5 years' Global Positioning System (GPS) derived Zenith Tropospheric Delay (ZTD) series from 25 stations of the Crustal Movement Observation Network of China (CMONOC). Then we study the effects of the models on satellite positioning by using various Precise Point Positioning (PPP) cases with different tropospheric delay resolutions, the observation data processed in PPP is from 21 base stations of CMONOC for a whole year of 2012. The results show that: (1) the Root Mean Square (RMS) of the IGGtrop model is about 4.4 cm, which improves the accuracy of ZTD estimations by about 24% for EGNOS and 19% for UNB3m; (2) The positioning error in the vertical component of the PPP solution obtained by using the IGGtrop model is about 15.0 cm, which is about 30% and 21% smaller than those of the EGNOS and UNB3m models, respectively. In summary, the IGGtrop model achieves the best performance among the three models in the Chinese region. PMID- 26805835 TI - A Pedestrian Detection Scheme Using a Coherent Phase Difference Method Based on 2D Range-Doppler FMCW Radar. AB - For an automotive pedestrian detection radar system, fast-ramp based 2D range Doppler Frequency Modulated Continuous Wave (FMCW) radar is effective for distinguishing between moving targets and unwanted clutter. However, when a weak moving target such as a pedestrian exists together with strong clutter, the pedestrian may be masked by the side-lobe of the clutter even though they are notably separated in the Doppler dimension. To prevent this problem, one popular solution is the use of a windowing scheme with a weighting function. However, this method leads to a spread spectrum, so the pedestrian with weak signal power and slow Doppler may also be masked by the main-lobe of clutter. With a fast-ramp based FMCW radar, if the target is moving, the complex spectrum of the range- Fast Fourier Transform (FFT) is changed with a constant phase difference over ramps. In contrast, the clutter exhibits constant phase irrespective of the ramps. Based on this fact, in this paper we propose a pedestrian detection for highly cluttered environments using a coherent phase difference method. By detecting the coherent phase difference from the complex spectrum of the range FFT, we first extract the range profile of the moving pedestrians. Then, through the Doppler FFT, we obtain the 2D range-Doppler map for only the pedestrian. To test the proposed detection scheme, we have developed a real-time data logging system with a 24 GHz FMCW transceiver. In laboratory tests, we verified that the signal processing results from the proposed method were much better than those expected from the conventional 2D FFT-based detection method. PMID- 26805836 TI - Non-Cooperative Target Imaging and Parameter Estimation with Narrowband Radar Echoes. AB - This study focuses on the rotating target imaging and parameter estimation with narrowband radar echoes, which is essential for radar target recognition. First, a two-dimensional (2D) imaging model with narrowband echoes is established in this paper, and two images of the target are formed on the velocity-acceleration plane at two neighboring coherent processing intervals (CPIs). Then, the rotating velocity (RV) is proposed to be estimated by utilizing the relationship between the positions of the scattering centers among two images. Finally, the target image is rescaled to the range-cross-range plane with the estimated rotational parameter. The validity of the proposed approach is confirmed using numerical simulations. PMID- 26805837 TI - EMD-Based Symbolic Dynamic Analysis for the Recognition of Human and Nonhuman Pyroelectric Infrared Signals. AB - In this paper, we propose an effective human and nonhuman pyroelectric infrared (PIR) signal recognition method to reduce PIR detector false alarms. First, using the mathematical model of the PIR detector, we analyze the physical characteristics of the human and nonhuman PIR signals; second, based on the analysis results, we propose an empirical mode decomposition (EMD)-based symbolic dynamic analysis method for the recognition of human and nonhuman PIR signals. In the proposed method, first, we extract the detailed features of a PIR signal into five symbol sequences using an EMD-based symbolization method, then, we generate five feature descriptors for each PIR signal through constructing five probabilistic finite state automata with the symbol sequences. Finally, we use a weighted voting classification strategy to classify the PIR signals with their feature descriptors. Comparative experiments show that the proposed method can effectively classify the human and nonhuman PIR signals and reduce PIR detector's false alarms. PMID- 26805838 TI - Vision-Based People Detection System for Heavy Machine Applications. AB - This paper presents a vision-based people detection system for improving safety in heavy machines. We propose a perception system composed of a monocular fisheye camera and a LiDAR. Fisheye cameras have the advantage of a wide field-of-view, but the strong distortions that they create must be handled at the detection stage. Since people detection in fisheye images has not been well studied, we focus on investigating and quantifying the impact that strong radial distortions have on the appearance of people, and we propose approaches for handling this specificity, adapted from state-of-the-art people detection approaches. These adaptive approaches nevertheless have the drawback of high computational cost and complexity. Consequently, we also present a framework for harnessing the LiDAR modality in order to enhance the detection algorithm for different camera positions. A sequential LiDAR-based fusion architecture is used, which addresses directly the problem of reducing false detections and computational cost in an exclusively vision-based system. A heavy machine dataset was built, and different experiments were carried out to evaluate the performance of the system. The results are promising, in terms of both processing speed and performance. PMID- 26805839 TI - Intravehicular, Short- and Long-Range Communication Information Fusion for Providing Safe Speed Warnings. AB - Inappropriate speed is a relevant concurrent factor in many traffic accidents. Moreover, in recent years, traffic accidents numbers in Spain have fallen sharply, but this reduction has not been so significant on single carriageway roads. These infrastructures have less equipment than high-capacity roads, therefore measures to reduce accidents on them should be implemented in vehicles. This article describes the development and analysis of the impact on the driver of a warning system for the safe speed on each road section in terms of geometry, the presence of traffic jams, weather conditions, type of vehicle and actual driving conditions. This system is based on an application for smartphones and includes knowledge of the vehicle position via Ground Positioning System (GPS), access to intravehicular information from onboard sensors through the Controller Area Network (CAN) bus, vehicle data entry by the driver, access to roadside information (short-range communications) and access to a centralized server with information about the road in the current and following sections of the route (long-range communications). Using this information, the system calculates the safe speed, recommends the appropriate speed in advance in the following sections and provides warnings to the driver. Finally, data are sent from vehicles to a server to generate new information to disseminate to other users or to supervise drivers' behaviour. Tests in a driving simulator have been used to define the system warnings and Human Machine Interface (HMI) and final tests have been performed on real roads in order to analyze the effect of the system on driver behavior. PMID- 26805840 TI - Parallel Imaging of 3D Surface Profile with Space-Division Multiplexing. AB - We have developed a modified optical frequency domain imaging (OFDI) system that performs parallel imaging of three-dimensional (3D) surface profiles by using the space division multiplexing (SDM) method with dual-area swept sourced beams. We have also demonstrated that 3D surface information for two different areas could be well obtained in a same time with only one camera by our method. In this study, double field of views (FOVs) of 11.16 mm * 5.92 mm were achieved within 0.5 s. Height range for each FOV was 460 um and axial and transverse resolutions were 3.6 and 5.52 um, respectively. PMID- 26805841 TI - Interferometric Laser Scanner for Direction Determination. AB - In this paper, we explore the potential capabilities of new laser scanning-based method for direction determination. The method for fully coherent beams is extended to the case when interference pattern is produced in the turbulent atmosphere by two partially coherent sources. The performed theoretical analysis identified the conditions under which stable pattern may form on extended paths of 0.5-10 km in length. We describe a method for selecting laser scanner parameters, ensuring the necessary operability range in the atmosphere for any possible turbulence characteristics. The method is based on analysis of the mean intensity of interference pattern, formed by two partially coherent sources of optical radiation. Visibility of interference pattern is estimated as a function of propagation pathlength, structure parameter of atmospheric turbulence, and spacing of radiation sources, producing the interference pattern. It is shown that, when atmospheric turbulences are moderately strong, the contrast of interference pattern of laser scanner may ensure its applicability at ranges up to 10 km. PMID- 26805842 TI - Vision-Based Georeferencing of GPR in Urban Areas. AB - Ground Penetrating Radar (GPR) surveying is widely used to gather accurate knowledge about the geometry and position of underground utilities. The sensor arrays need to be coupled to an accurate positioning system, like a geodetic grade Global Navigation Satellite System (GNSS) device. However, in urban areas this approach is not always feasible because GNSS accuracy can be substantially degraded due to the presence of buildings, trees, tunnels, etc. In this work, a photogrammetric (vision-based) method for GPR georeferencing is presented. The method can be summarized in three main steps: tie point extraction from the images acquired during the survey, computation of approximate camera extrinsic parameters and finally a refinement of the parameter estimation using a rigorous implementation of the collinearity equations. A test under operational conditions is described, where accuracy of a few centimeters has been achieved. The results demonstrate that the solution was robust enough for recovering vehicle trajectories even in critical situations, such as poorly textured framed surfaces, short baselines, and low intersection angles. PMID- 26805843 TI - A Two Fiber Bragg Gratings Sensing System to Monitor the Torque of Rotating Shaft. AB - By fixing two FBGs on the surface of a rotating shaft along the direction of +/- 45 degrees and using dynamic wavelength demodulation technology, we propose an optical fiber sensing system to monitor the driving torque and torsion angle of the rotating shaft. In theory, the dependence relation of the dynamic difference of central wavelengths on the torque and torsion angle of the rotating shaft has been deduced. To verify an optical fiber sensing system, a series of sensing experiments have been completed and the measured data are approximately consistent with the theoretical analysis. The difference of two central wavelengths can be expressed as the sum of two parts: a "DC" part and a harmonic "AC" part. The driving torque or torsion angle is linear with the "DC" part of the difference of two central wavelengths, the harmonic "AC" part, meaning the torsion angle vibration, illustrates that periodic vibration torque may be caused by inhomogeneous centrifugal forces or inhomogeneous additional torques produced by the driving system and the load. PMID- 26805844 TI - Analysis of a Segmented Annular Coplanar Capacitive Tilt Sensor with Increased Sensitivity. AB - An investigation of a segmented annular coplanar capacitor is presented. We focus on its theoretical model, and a mathematical expression of the capacitance value is derived by solving a Laplace equation with Hankel transform. The finite element method is employed to verify the analytical result. Different control parameters are discussed, and each contribution to the capacitance value of the capacitor is obtained. On this basis, we analyze and optimize the structure parameters of a segmented coplanar capacitive tilt sensor, and three models with different positions of the electrode gap are fabricated and tested. The experimental result shows that the model (whose electrode-gap position is 10 mm from the electrode center) realizes a high sensitivity: 0.129 pF/ degrees with a non-linearity of <0.4% FS (full scale of +/- 40 degrees ). This finding offers plenty of opportunities for various measurement requirements in addition to achieving an optimized structure in practical design. PMID- 26805846 TI - A Novel Photoelectrochemical Biosensor for Tyrosinase and Thrombin Detection. AB - A novel photoelectrochemical biosensor for step-by-step assay of tyrosinase and thrombin was fabricated based on the specific interactions between the designed peptide and the target enzymes. A peptide chain with a special sequence which contains a positively charged lysine-labeled terminal, tyrosine at the other end and a cleavage site recognized by thrombin between them was designed. The designed peptide can be fixed on surface of the CdTe quantum dots (QDs)-modified indium-tin oxide (ITO) electrode through electrostatic attraction to construct the photoelectrochemical biosensor. The tyrosinase target can catalyze the oxidization of tyrosine by oxygen into ortho-benzoquinone residues, which results in a decrease in the sensor photocurrent. Subsequently, the cleavage site could be recognized and cut off by another thrombin target, restoring the sensor photocurrent. The decrease or increase of photocurrent in the sensor enables us to assay tyrosinase and thrombin. Thus, the detection of tyrosinase and thrombin can be achieved in the linear range from 2.6 to 32 MUg/mL and from 4.5 to 100 MUg/mL with detection limits of 1.5 MUg/mL and 1.9 MUg/mL, respectively. Most importantly, this strategy shall allow us to detect different classes of enzymes simultaneously by designing various enzyme-specific peptide substrates. PMID- 26805845 TI - Graphene: The Missing Piece for Cancer Diagnosis? AB - This paper reviews recent advances in graphene-based biosensors development in order to obtain smaller and more portable devices with better performance for earlier cancer detection. In fact, the potential of Graphene for sensitive detection and chemical/biological free-label applications results from its exceptional physicochemical properties such as high electrical and thermal conductivity, aspect-ratio, optical transparency and remarkable mechanical and chemical stability. Herein we start by providing a general overview of the types of graphene and its derivatives, briefly describing the synthesis procedure and main properties. It follows the reference to different routes to engineer the graphene surface for sensing applications with organic biomolecules and nanoparticles for the development of advanced biosensing platforms able to detect/quantify the characteristic cancer biomolecules in biological fluids or overexpressed on cancerous cells surface with elevated sensitivity, selectivity and stability. We then describe the application of graphene in optical imaging methods such as photoluminescence and Raman imaging, electrochemical sensors for enzymatic biosensing, DNA sensing, and immunosensing. The bioquantification of cancer biomarkers and cells is finally discussed, particularly electrochemical methods such as voltammetry and amperometry which are generally adopted transducing techniques for the development of graphene based sensors for biosensing due to their simplicity, high sensitivity and low-cost. To close, we discuss the major challenges that graphene based biosensors must overcome in order to reach the necessary standards for the early detection of cancer biomarkers by providing reliable information about the patient disease stage. PMID- 26805847 TI - A Machine Learning Framework for Gait Classification Using Inertial Sensors: Application to Elderly, Post-Stroke and Huntington's Disease Patients. AB - Machine learning methods have been widely used for gait assessment through the estimation of spatio-temporal parameters. As a further step, the objective of this work is to propose and validate a general probabilistic modeling approach for the classification of different pathological gaits. Specifically, the presented methodology was tested on gait data recorded on two pathological populations (Huntington's disease and post-stroke subjects) and healthy elderly controls using data from inertial measurement units placed at shank and waist. By extracting features from group-specific Hidden Markov Models (HMMs) and signal information in time and frequency domain, a Support Vector Machines classifier (SVM) was designed and validated. The 90.5% of subjects was assigned to the right group after leave-one-subject-out cross validation and majority voting. The long term goal we point to is the gait assessment in everyday life to early detect gait alterations. PMID- 26805848 TI - A Novel Pedestrian Navigation Algorithm for a Foot-Mounted Inertial-Sensor-Based System. AB - This paper proposes a novel zero velocity update (ZUPT) method for a foot-mounted pedestrian navigation system (PNS). First, the error model of the PNS is developed and a Kalman filter is built based on the error model. Second, a novel zero velocity detection algorithm based on the variations in speed over a gait cycle is proposed. A finite state machine including three states is employed to model a gait cycle. The state transition conditions are determined based on speed using a sliding window. Third, the ZUPT software flow is illustrated and described. Finally, the performances of the proposed method and other methods are examined and compared experimentally. The experimental results show that the mean relative accuracy of the proposed method is 0.89% under various motion modes. PMID- 26805849 TI - Segmentation of Planar Surfaces from Laser Scanning Data Using the Magnitude of Normal Position Vector for Adaptive Neighborhoods. AB - Diverse approaches to laser point segmentation have been proposed since the emergence of the laser scanning system. Most of these segmentation techniques, however, suffer from limitations such as sensitivity to the choice of seed points, lack of consideration of the spatial relationships among points, and inefficient performance. In an effort to overcome these drawbacks, this paper proposes a segmentation methodology that: (1) reduces the dimensions of the attribute space; (2) considers the attribute similarity and the proximity of the laser point simultaneously; and (3) works well with both airborne and terrestrial laser scanning data. A neighborhood definition based on the shape of the surface increases the homogeneity of the laser point attributes. The magnitude of the normal position vector is used as an attribute for reducing the dimension of the accumulator array. The experimental results demonstrate, through both qualitative and quantitative evaluations, the outcomes' high level of reliability. The proposed segmentation algorithm provided 96.89% overall correctness, 95.84% completeness, a 0.25 m overall mean value of centroid difference, and less than 1 degrees of angle difference. The performance of the proposed approach was also verified with a large dataset and compared with other approaches. Additionally, the evaluation of the sensitivity of the thresholds was carried out. In summary, this paper proposes a robust and efficient segmentation methodology for abstraction of an enormous number of laser points into plane information. PMID- 26805850 TI - Next Place Prediction Based on Spatiotemporal Pattern Mining of Mobile Device Logs. AB - Due to the recent explosive growth of location-aware services based on mobile devices, predicting the next places of a user is of increasing importance to enable proactive information services. In this paper, we introduce a data-driven framework that aims to predict the user's next places using his/her past visiting patterns analyzed from mobile device logs. Specifically, the notion of the spatiotemporal-periodic (STP) pattern is proposed to capture the visits with spatiotemporal periodicity by focusing on a detail level of location for each individual. Subsequently, we present algorithms that extract the STP patterns from a user's past visiting behaviors and predict the next places based on the patterns. The experiment results obtained by using a real-world dataset show that the proposed methods are more effective in predicting the user's next places than the previous approaches considered in most cases. PMID- 26805851 TI - Real-time Imaging Orientation Determination System to Verify Imaging Polarization Navigation Algorithm. AB - Bio-inspired imaging polarization navigation which can provide navigation information and is capable of sensing polarization information has advantages of high-precision and anti-interference over polarization navigation sensors that use photodiodes. Although all types of imaging polarimeters exist, they may not qualify for the research on the imaging polarization navigation algorithm. To verify the algorithm, a real-time imaging orientation determination system was designed and implemented. Essential calibration procedures for the type of system that contained camera parameter calibration and the inconsistency of complementary metal oxide semiconductor calibration were discussed, designed, and implemented. Calibration results were used to undistort and rectify the multi camera system. An orientation determination experiment was conducted. The results indicated that the system could acquire and compute the polarized skylight images throughout the calibrations and resolve orientation by the algorithm to verify in real-time. An orientation determination algorithm based on image processing was tested on the system. The performance and properties of the algorithm were evaluated. The rate of the algorithm was over 1 Hz, the error was over 0.313 degrees , and the population standard deviation was 0.148 degrees without any data filter. PMID- 26805852 TI - A Context-Aware Mobile User Behavior-Based Neighbor Finding Approach for Preference Profile Construction. AB - In this paper, a new approach is adopted to update the user preference profile by seeking users with similar interests based on the context obtainable for a mobile network instead of from desktop networks. The trust degree between mobile users is calculated by analyzing their behavior based on the context, and then the approximate neighbors are chosen by combining the similarity of the mobile user preference and the trust degree. The approach first considers the communication behaviors between mobile users, the mobile network services they use as well as the corresponding context information. Then a similarity degree of the preference between users is calculated with the evaluation score of a certain mobile web service provided by a mobile user. Finally, based on the time attenuation function, the users with similar preference are found, through which we can dynamically update the target user's preference profile. Experiments are then conducted to test the effect of the context on the credibility among mobile users, the effect of time decay factors and trust degree thresholds. Simulation shows that the proposed approach outperforms two other methods in terms of Recall Ratio, Precision Ratio and Mean Absolute Error, because neither of them consider the context mobile information. PMID- 26805853 TI - An Adaptive INS-Aided PLL Tracking Method for GNSS Receivers in Harsh Environments. AB - As the weak link in global navigation satellite system (GNSS) signal processing, the phase-locked loop (PLL) is easily influenced with frequent cycle slips and loss of lock as a result of higher vehicle dynamics and lower signal-to-noise ratios. With inertial navigation system (INS) aid, PLLs' tracking performance can be improved. However, for harsh environments with high dynamics and signal attenuation, the traditional INS-aided PLL with fixed loop parameters has some limitations to improve the tracking adaptability. In this paper, an adaptive INS aided PLL capable of adjusting its noise bandwidth and coherent integration time has been proposed. Through theoretical analysis, the relation between INS-aided PLL phase tracking error and carrier to noise density ratio (C/N0), vehicle dynamics, aiding information update time, noise bandwidth, and coherent integration time has been built. The relation formulae are used to choose the optimal integration time and bandwidth for a given application under the minimum tracking error criterion. Software and hardware simulation results verify the correctness of the theoretical analysis, and demonstrate that the adaptive tracking method can effectively improve the PLL tracking ability and integrated GNSS/INS navigation performance. For harsh environments, the tracking sensitivity is increased by 3 to 5 dB, velocity errors are decreased by 36% to 50% and position errors are decreased by 6% to 24% when compared with other INS-aided PLL methods. PMID- 26805855 TI - Biologically Active Oxylipins from Enzymatic and Nonenzymatic Routes in Macroalgae. AB - Marine algae are rich and heterogeneous sources of great chemical diversity, among which oxylipins are a well-recognized class of natural products. Algal oxylipins comprise an assortment of oxygenated, halogenated, and unsaturated functional groups and also several carbocycles, varying in ring size and position in lipid chain. Besides the discovery of structurally diverse oxylipins in macroalgae, research has recently deciphered the role of some of these metabolites in the defense and innate immunity of photosynthetic marine organisms. This review is an attempt to comprehensively cover the available literature on the chemistry, biosynthesis, ecology, and potential bioactivity of oxylipins from marine macroalgae. For a better understanding, enzymatic and nonenzymatic routes were separated; however, both processes often occur concomitantly and may influence each other, even producing structurally related molecules. PMID- 26805856 TI - Liquid Chromatography-Mass Spectrometry-Based Rapid Secondary-Metabolite Profiling of Marine Pseudoalteromonas sp. M2. AB - The ocean is a rich resource of flora, fauna, and food. A wild-type bacterial strain showing confluent growth on marine agar with antibacterial activity was isolated from marine water, identified using 16S rDNA sequence analysis as Pseudoalteromonas sp., and designated as strain M2. This strain was found to produce various secondary metabolites including quinolone alkaloids. Using high resolution mass spectrometry (MS) and nuclear magnetic resonance (NMR) analysis, we identified nine secondary metabolites of 4-hydroxy-2-alkylquinoline (pseudane III, IV, V, VI, VII, VIII, IX, X, and XI). Additionally, this strain produced two novel, closely related compounds, 2-isopentylqunoline-4-one and 2-(2,3 dimetylbutyl)qunoline-4-(1H)-one, which have not been previously reported from marine bacteria. From the metabolites produced by Pseudoalteromonas sp. M2, 2 (2,3-dimethylbutyl)quinolin-4-one, pseudane-VI, and pseudane-VII inhibited melanin synthesis in Melan-A cells by 23.0%, 28.2%, and 42.7%, respectively, wherein pseudane-VII showed the highest inhibition at 8 ug/mL. The results of this study suggest that liquid chromatography (LC)-MS/MS-based metabolite screening effectively improves the efficiency of novel metabolite discovery. Additionally, these compounds are promising candidates for further bioactivity development. PMID- 26805857 TI - Stomach Chitinase from Japanese Sardine Sardinops melanostictus: Purification, Characterization, and Molecular Cloning of Chitinase Isozymes with a Long Linker. AB - Fish express two different chitinases, acidic fish chitinase-1 (AFCase-1) and acidic fish chitinase-2 (AFCase-2), in the stomach. AFCase-1 and AFCase-2 have different degradation patterns, as fish efficiently degrade chitin ingested as food. For a comparison with the enzymatic properties and the primary structures of chitinase isozymes obtained previously from the stomach of demersal fish, in this study, we purified chitinase isozymes from the stomach of Japanese sardine Sardinops melanostictus, a surface fish that feeds on plankton, characterized the properties of these isozymes, and cloned the cDNAs encoding chitinases. We also predicted 3D structure models using the primary structures of S. melanostictus stomach chitinases. Two chitinase isozymes, SmeChiA (45 kDa) and SmeChiB (56 kDa), were purified from the stomach of S. melanostictus. Moreover, two cDNAs, SmeChi-1 encoding SmeChiA, and SmeChi-2 encoding SmeChiB were cloned. The linker regions of the deduced amino acid sequences of SmeChi-1 and SmeChi-2 (SmeChi-1 and SmeChi-2) are the longest among the fish stomach chitinases. In the cleavage pattern groups toward short substrates and the phylogenetic tree analysis, SmeChi 1 and SmeChi-2 were classified into AFCase-1 and AFCase-2, respectively. SmeChi-1 and SmeChi-2 had catalytic domains that consisted of a TIM-barrel (beta/alpha)8 fold structure and a deep substrate-binding cleft. This is the first study showing the 3D structure models of fish stomach chitinases. PMID- 26805859 TI - Basic Characteristics and Spatial Patterns of Pseudo-Settlements--Taking Dalian as An Example. AB - A person's living behavior patterns are closely related to three types of settlements: real-life settlements, imagined settlements, and pseudo-settlements. The term "pseudo-settlement" (PS) refers to the places that are selectively recorded and represented after the mass media chose and restructure the residence information. As the mass media rapidly develops and people's way of obtaining information gradually change, PS has already become one of the main ways for people to recognize and understand real-life settlements, as well as describe their impressions of imagined settlements. PS also has a profound impact on tourism, employment, investment, migration, real estate development, etc. Thus, the study of PSs has important theoretical and practical significance. This paper proposes to put forward residential quarters where the mass media is displayed as the object of study and establishes the pseudo-settlement index system of Dalian in and elaborate analysis of the concept of PSs. From three aspects, including pseudo-buildings, pseudo-districts and pseudo-culture, this paper uses the ArcGIS 10.0 kernel density (spacial analyst) to analyze and interpret the basic characteristics and spatial patterns of 14 elements of the PS in Dalian. Through systemic clustering analysis, it identifies eight major types of PSs in Dalian. Then it systematically elaborates current situations and characteristics of the spatial pattern of PSs in Dalian, namely: regionally concentrated, widely scattered and blank spaces without pseudo-settlements. Finally, this paper discusses the mechanism of formation of PSs in Dalian. PMID- 26805858 TI - Effects of Halide Ions on the Carbamidocyclophane Biosynthesis in Nostoc sp. CAVN2. AB - In this study, the influence of halide ions on [7.7]paracyclophane biosynthesis in the cyanobacterium Nostoc sp. CAVN2 was investigated. In contrast to KI and KF, supplementation of the culture medium with KCl or KBr resulted not only in an increase of growth but also in an up-regulation of carbamidocyclophane production. LC-MS analysis indicated the presence of chlorinated, brominated, but also non-halogenated derivatives. In addition to 22 known cylindrocyclophanes and carbamidocyclophanes, 27 putative congeners have been detected. Nine compounds, carbamidocyclophanes M-U, were isolated, and their structural elucidation by 1D and 2D NMR experiments in combination with HRMS and ECD analysis revealed that they are brominated analogues of chlorinated carbamidocyclophanes. Quantification of the carbamidocyclophanes showed that chloride is the preferably utilized halide, but incorporation is reduced in the presence of bromide. Evaluation of the antibacterial activity of 30 [7.7]paracyclophanes and related derivatives against selected pathogenic Gram-positive and Gram-negative bacteria exhibited remarkable effects especially against methicillin- and vancomycin-resistant staphylococci and Mycobacterium tuberculosis. For deeper insights into the mechanisms of biosynthesis, the carbamidocyclophane biosynthetic gene cluster in Nostoc sp. CAVN2 was studied. The gene putatively coding for the carbamoyltransferase has been identified. Based on bioinformatic analyses, a possible biosynthetic assembly is discussed. PMID- 26805860 TI - Measuring Indoor Air Quality and Engaging California Indian Stakeholders at the Win-River Resort and Casino: Collaborative Smoke-Free Policy Development. AB - Most casinos owned by sovereign American Indian nations allow smoking, even in U.S. states such as California where state laws restrict workplace smoking. Collaborations between casinos and public health workers are needed to promote smoke-free policies that protect workers and patrons from secondhand tobacco smoke (SHS) exposure and risks. Over seven years, a coalition of public health professionals provided technical assistance to the Redding Rancheria tribe in Redding, California in establishing a smoke-free policy at the Win-River Resort and Casino. The coalition provided information to the casino general manager that included site-specific measurement of employee and visitor PM2.5 personal exposure, area concentrations of airborne nicotine and PM2.5, visitor urinary cotinine, and patron and staff opinions (surveys, focus groups, and a Town Hall meeting). The manager communicated results to tribal membership, including evidence of high SHS exposures and support for a smoke-free policy. Subsequently, in concert with hotel expansion, the Redding Rancheria Tribal Council voted to accept a 100% restriction of smoking inside the casino, whereupon PM2.5 exposure in main smoking areas dropped by 98%. A 70% partial-smoke-free policy was instituted ~1 year later in the face of revenue loss. The success of the collaboration in promoting a smoke-free policy, and the key element of air quality feedback, which appeared to be a central driver, may provide a model for similar efforts. PMID- 26805861 TI - Maternal and Neonatal Levels of Perfluoroalkyl Substances in Relation to Gestational Weight Gain. AB - Perfluoroalkyl substances (PFASs) are ubiquitous, persistent pollutants widely used in the production of common household and consumer goods. There is a limited body of literature suggesting that these chemicals may alter metabolic pathways and growth trajectories. The relationship between prenatal exposures to these chemicals and gestational weight gain (GWG) has received limited attention. One objective was to analyze the associations among maternal plasma levels of three common perfluoroalkyl substances (perfluorooctanoate (PFOA), perfluorooctanesulfonate (PFOS), perfluorohexanesulfanoate (PFHxS)) and GWG. Additionally, we explored whether GWG was associated with cord blood PFAS levels. This study utilized data collected in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2001 pregnant women. Our analysis quantified associations between (1) maternal PFAS concentrations and GWG and (2) GWG and cord blood PFAS concentrations. Maternal PFOS concentrations were positively associated with GWG (beta = 0.39 95% CI: 0.02, 0.75). Interquartile increases in GWG were significantly associated with elevated cord blood PFOA (OR = 1.33; 95% CI: 1.13 to 1.56) and PFOS (OR = 1.20; 95% CI: 1.03 to 1.40) concentrations. No statistically significant associations were observed between GWG and either measure of PFHxS. These findings warrant elucidation of the potential underlying mechanisms. PMID- 26805862 TI - Airborne Particulate Matter in Two Multi-Family Green Buildings: Concentrations and Effect of Ventilation and Occupant Behavior. AB - There are limited data on air quality parameters, including airborne particulate matter (PM) in residential green buildings, which are increasing in prevalence. Exposure to PM is associated with cardiovascular and pulmonary diseases, and since Americans spend almost 90% of their time indoors, residential exposures may substantially contribute to overall airborne PM exposure. Our objectives were to: (1) measure various PM fractions longitudinally in apartments in multi-family green buildings with natural (Building E) and mechanical (Building L) ventilation; (2) compare indoor and outdoor PM mass concentrations and their ratios (I/O) in these buildings, taking into account the effects of occupant behavior; and (3) evaluate the effect of green building designs and operations on indoor PM. We evaluated effects of ventilation, occupant behaviors, and overall building design on PM mass concentrations and I/O. Median PMTOTAL was higher in Building E (56 ug/m3) than in Building L (37 ug/m3); I/O was higher in Building E (1.3-2.0) than in Building L (0.5-0.8) for all particle size fractions. Our data show that the building design and occupant behaviors that either produce or dilute indoor PM (e.g., ventilation systems, combustion sources, and window operation) are important factors affecting residents' exposure to PM in residential green buildings. PMID- 26805864 TI - Rainfall-Runoff Simulations to Assess the Potential of SuDS for Mitigating Flooding in Highly Urbanized Catchments. AB - Sustainable Urban Drainage Systems (SuDS) constitute an alternative to conventional drainage when managing stormwater in cities, reducing the impact of urbanization by decreasing the amount of runoff generated by a rainfall event. This paper shows the potential benefits of installing different types of SuDS in preventing flooding in comparison with the common urban drainage strategies consisting of sewer networks of manholes and pipes. The impact of these systems on urban water was studied using Geographic Information Systems (GIS), which are useful tools when both delineating catchments and parameterizing the elements that define a stormwater drainage system. Taking these GIS-based data as inputs, a series of rainfall-runoff simulations were run in a real catchment located in the city of Donostia (Northern Spain) using stormwater computer models, in order to compare the flow rates and depths produced by a design storm before and after installing SuDS. The proposed methodology overcomes the lack of precision found in former GIS-based stormwater approaches when dealing with the modeling of highly urbanized catchments, while the results demonstrated the usefulness of these systems in reducing the volume of water generated after a rainfall event and their ability to prevent localized flooding and surcharges along the sewer network. PMID- 26805863 TI - Reliability and Construct Validity of Two Versions of Chalder Fatigue Scale among the General Population in Mainland China. AB - The 14-item Chalder Fatigue Scale (CFS) is widely used, while the 11-item version is seldom to be found in current research in mainland China. The objectives of the present study is to compare the reliability and construct validity between these two versions and to confirm which may be better for the mainland Chinese setting. Based on a cross-sectional health survey with a constructive questionnaire, 1887 individuals aged 18 years or above were selected. Socio demographic, health-related, gynecological data were collected, and 11-item and 14-item Chalder Fatigue Scale (CFS) were used to assess fatigue. Confirmatory factor analysis and exploratory structural equation modeling (ESEM) were performed to test the fit of models of the two versions. Confirmatory factor analysis of the two versions of CFS did not support the two-factor theorized models. In addition, a three-factor ESEM model of the 11-item version, but not the 14-item version, showed better factor structure and fitness than the other models examined. Both the versions had good internal consistency reliability and a satisfactory internal consistency (Omega = 0.78-0.96, omega coefficient indicates the internal consistency reliability) was obtained from the optimal model. This study provided evidence for satisfactory reliability and structural validity for the three-factor model of the 11-item version, which was proven to be superior to the 14-item version for this data. PMID- 26805865 TI - Occupational Disparities in the Association between Self-Reported Salt-Eating Habit and Hypertension in Older Adults in Xiamen, China. AB - Blood pressure responses to sodium intake are heterogeneous among populations. Few studies have assessed occupational disparities in the association between sodium intake and hypertension in older people. We used cross-sectional data from 14,292 participants aged 60 years or older in Xiamen, China, in 2013. Self reported salt-eating habit was examined with three levels: low, medium, and high. The main lifetime occupation was classified into indoor laborer and outdoor laborer. Multivariable logistic regression was used to examine associations of hypertension with self-reported salt-eating habit, main lifetime occupation, and their interactions by adjusting for some covariates, with further stratification by sex. Overall, 13,738 participants had complete data, of whom 30.22% had hypertension. The prevalence of hypertension was 31.57%, 28.63%, and 31.97% in participants who reported to have low, medium, and high salt-eating habit, respectively. Outdoor laborers presented significantly lower prevalence of hypertension than indoor laborers (26.04% vs. 34.26%, p < 0.001). Indoor laborers with high salt-eating habit had the greatest odds of hypertension (OR = 1.32, 95% CI [1.09-1.59]). An increased trend of odds in eating habit as salt-heavier was presented in indoor laborers (p-trend = 0.048), especially for women (p-trend = 0.001). No clear trend presented in men. Conclusively, sex-specific occupational disparities exist in the association between self-reported salt-eating habit and hypertension in older individuals. Overlooking the potential moderating role of sex and occupation might affect the relationship between sodium intake and hypertension. PMID- 26805866 TI - Diversity of Bacterial Communities on Four Frequently Used Surfaces in a Large Brazilian Teaching Hospital. AB - Frequently used hand-touch surfaces in hospital settings have been implicated as a vehicle of microbial transmission. In this study, we aimed to investigate the overall bacterial population on four frequently used surfaces using a culture independent Illumina massively parallel sequencing approach of the 16S rRNA genes. Surface samples were collected from four sites, namely elevator buttons (EB), bank machine keyboard buttons (BMKB), restroom surfaces, and the employee biometric time clock system (EBTCS), in a large public and teaching hospital in Sao Paulo. Taxonomical composition revealed the abundance of Firmicutes phyla, followed by Actinobacteria and Proteobacteria, with a total of 926 bacterial families and 2832 bacterial genera. Moreover, our analysis revealed the presence of some potential pathogenic bacterial genera, including Salmonella enterica, Klebsiella pneumoniae, and Staphylococcus aureus. The presence of these pathogens in frequently used surfaces enhances the risk of exposure to any susceptible individuals. Some of the factors that may contribute to the richness of bacterial diversity on these surfaces are poor personal hygiene and ineffective routine schedules of cleaning, sanitizing, and disinfecting. Strict standards of infection control in hospitals and increased public education about hand hygiene are recommended to decrease the risk of transmission in hospitals among patients. PMID- 26805867 TI - Fat Mass Centile Charts for Brazilian Children and Adolescents and the Identification of the Roles of Socioeconomic Status and Physical Fitness on Fat Mass Development. AB - This paper presents fat mass centile charts for Brazilian youth and investigates the roles of socioeconomic status and physical fitness (PF) on fat mass (FM) development. Two northeast Brazilian samples were used: a cross-sectional sample of 3659 (1921 girls) aged 8 to 16 years and a mixed-longitudinal series of cohorts (8-10, 10-12, 12-14, 14-16 years) with 250 boys and 250 girls. A measure of somatic maturity was used as a marker of biological maturation; PF comprised agility, explosive and static strength, and aerobic capacity. Socioeconomic status was based on school attended; public or private. Slaughter's anthropometric equations were used to estimate FM. Percentile charts was constructed using the LMS method. HLM (Hierarchical Linear Model) 7 software modeled FM changes, identifying inter-individual differences and their covariates. Girls and boys had different FM percentile values at each age; FM increased nonlinearly in both girls and boys. Higher PF levels reduced FM changes across time in both sexes. Sex-specific non-linear FM references were provided representing important tools for nutritionists, pediatriciann and educators. Physical fitness levels were found to act as a protective factor in FM increases. As such, we emphasize PF importance as a putative health marker and highlight the need for its systematic development across the school years. PMID- 26805869 TI - Economic Estimation of the Losses Caused by Surface Water Pollution Accidents in China From the Perspective of Water Bodies' Functions. AB - The number of surface water pollution accidents (abbreviated as SWPAs) has increased substantially in China in recent years. Estimation of economic losses due to SWPAs has been one of the focuses in China and is mentioned many times in the Environmental Protection Law of China promulgated in 2014. From the perspective of water bodies' functions, pollution accident damages can be divided into eight types: damage to human health, water supply suspension, fishery, recreational functions, biological diversity, environmental property loss, the accident's origin and other indirect losses. In the valuation of damage to people's life, the procedure for compensation of traffic accidents in China was used. The functional replacement cost method was used in economic estimation of the losses due to water supply suspension and loss of water's recreational functions. Damage to biological diversity was estimated by recovery cost analysis and damage to environmental property losses were calculated using pollutant removal costs. As a case study, using the proposed calculation procedure the economic losses caused by the major Songhuajiang River pollution accident that happened in China in 2005 have been estimated at 2263 billion CNY. The estimated economic losses for real accidents can sometimes be influenced by social and political factors, such as data authenticity and accuracy. Besides, one or more aspects in the method might be overestimated, underrated or even ignored. The proposed procedure may be used by decision makers for the economic estimation of losses in SWPAs. Estimates of the economic losses of pollution accidents could help quantify potential costs associated with increased risk sources along lakes/rivers but more importantly, highlight the value of clean water to society as a whole. PMID- 26805868 TI - High Levels of Persistent Problem Drinking in Women at High Risk for HIV in Kampala, Uganda: A Prospective Cohort Study. AB - The aim of this study was to describe the epidemiology of problem drinking in a cohort of women at high-risk of HIV in Kampala, Uganda. Overall, 1027 women at high risk of HIV infection were followed from 2008 to 2013. The CAGE and AUDIT questionnaires were used to identify problem drinkers in the cohort. Interviewer administered questionnaires were used to ascertain socio-demographic and behavioural factors. Blood and genital samples were tested for HIV and other sexually transmitted infections. At enrollment, most women (71%) reported using alcohol at least weekly and about a third reported having drunk alcohol daily for at least 2 weeks during the past 3 months. Over half (56%) were problem drinkers by CAGE at enrollment, and this was independently associated with vulnerability (being divorced/separated/widowed, less education, recruiting clients at bars/clubs, and forced sex at first sexual experience). Factors associated with problem drinking during follow-up included younger age, meeting clients in bars/clubs, number of clients, using drugs and HSV-2 infection. HIV prevalence was associated with drinking at enrollment, but not during follow-up. This longitudinal study found high levels of persistent problem drinking. Further research is needed to adapt and implement alcohol-focused interventions in vulnerable key populations in sub-Saharan Africa. PMID- 26805871 TI - Associations of Age, BMI, and Years of Menstruation with Proximal Femur Strength in Chinese Postmenopausal Women: A Cross-Sectional Study. AB - This study aimed to elucidate the associations of age, BMI, and years of menstruation with proximal femur strength in Chinese postmenopausal women, which may improve the prediction of hip fracture risk. A cross-sectional study was conducted in 1322 Chinese postmenopausal women recruited from communities. DXA images were used to generate bone mineral density (BMD) and geometric parameters, including cross-sectional area (CSA), outer diameter (OD), cortical thickness (CT), section modulus (SM), buckling ratio (BR) at the narrow neck (NN), intertrochanter (IT), and femoral shaft (FS). Relationships of age, BMI, and years of menstruation with bone phenotypes were analyzed with the adjustment of height, age at menarche, total daily physical activity, education, smoking status, calcium tablet intake, etc. Age was associated with lower BMD, CSA, CT, SM, and higher BR (p < 0.05), which indicated a weaker bone strength at the proximal femur. BMI and years of menstruation had the positive relationships with proximal femur strength (p < 0.05). Further analyses showed that the ranges of absolute value of change slope per year, per BMI or per year of menstruation were 0.14%-1.34%, 0.20%-2.70%, and 0.16%-0.98%, respectively. These results supported that bone strength deteriorated with aging and enhanced with higher BMI and longer time of years of menstruation in Chinese postmenopausal women. PMID- 26805870 TI - Association between Psychological Flexibility and Health Beliefs in the Uptake of Influenza Vaccination among People with Chronic Respiratory Diseases in Hong Kong. AB - It is common for elderly people and those with such chronic disorders as respiratory diseases to suffer severe complications from influenza, a viral infection. The voluntary uptake of vaccination is vital to the effectiveness of influenza prevention efforts. The Health Belief Model (HBM) is the most commonly used framework in the field of vaccination behavior to explain the decision that people make to accept or refuse vaccination. In addition, psychological flexibility is considered helpful in causing people to be open to adopting new practices that are consistent with their values. This study examined the role of psychological flexibility and health beliefs in predicting the uptake of influenza vaccination among people in Hong Kong. Eligible participants were Hong Kong permanent residents aged 18 years or above with a history of chronic respiratory diseases (CRD). A convenience sample of 255 patients was recruited to participate in a cross-sectional survey in which HBM components and factors of psychological flexibility were assessed. The following variables were found to be significant predictors of vaccination: age, smoking status, comorbidity, previous hospitalization, perceived susceptibility, perceived severity, and psychological flexibility. Enhancing psychological flexibility might be a potential new direction for motivating people to accept influenza vaccination. PMID- 26805872 TI - Branched Lateral Tail Fiber Organization in T5-Like Bacteriophages DT57C and DT571/2 is Revealed by Genetic and Functional Analysis. AB - The T5-like siphoviruses DT57C and DT571/2, isolated from horse feces, are very closely related to each other, and most of their structural proteins are also nearly identical to T5 phage. Their LTFs (L-shaped tail fibers), however, are composed of two proteins, LtfA and LtfB, instead of the single Ltf of bacteriophage T5. In silico and mutant analysis suggests a possible branched structure of DT57C and DT571/2 LTFs, where the LtfB protein is connected to the phage tail via the LtfA protein and with both proteins carrying receptor recognition domains. Such adhesin arrangement has not been previously recognized in siphoviruses. The LtfA proteins of our phages are found to recognize different host O-antigen types: E. coli O22-like for DT57C phage and E. coli O87 for DT571/2. LtfB proteins are identical in both phages and recognize another host receptor, most probably lipopolysaccharide (LPS) of E. coli O81 type. In these two bacteriophages, LTF function is essential to penetrate the shield of the host's O-antigens. We also demonstrate that LTF-mediated adsorption becomes superfluous when the non-specific cell protection by O-antigen is missing, allowing the phages to bind directly to their common secondary receptor, the outer membrane protein BtuB. The LTF independent adsorption was also demonstrated on an O22-like host mutant missing O-antigen O-acetylation, thus showing the biological value of this O-antigen modification for cell protection against phages. PMID- 26805873 TI - Experimental Inoculation of Egyptian Fruit Bats (Rousettus aegyptiacus) with Ebola Virus. AB - Colonized Egyptian fruit bats (Rousettus aegyptiacus), originating in South Africa, were inoculated subcutaneously with Ebola virus (EBOV). No overt signs of morbidity, mortality, or gross lesions were noted. Bats seroconverted by Day 10 16 post inoculation (p.i.), with the highest mean anti-EBOV IgG level on Day 28 p.i. EBOV RNA was detected in blood from one bat. In 16 other tissues tested, viral RNA distribution was limited and at very low levels. No seroconversion could be demonstrated in any of the control bats up to 28 days after in-contact exposure to subcutaneously-inoculated bats. The control bats were subsequently inoculated intraperitoneally, and intramuscularly with the same dose of EBOV. No mortality, morbidity or gross pathology was observed in these bats. Kinetics of immune response was similar to that in subcutaneously-inoculated bats. Viral RNA was more widely disseminated to multiple tissues and detectable in a higher proportion of individuals, but consistently at very low levels. Irrespective of the route of inoculation, no virus was isolated from tissues which tested positive for EBOV RNA. Viral RNA was not detected in oral, nasal, ocular, vaginal, penile and rectal swabs from any of the experimental groups. PMID- 26805874 TI - Docosahexaenoic Acid Ameliorates Fructose-Induced Hepatic Steatosis Involving ER Stress Response in Primary Mouse Hepatocytes. AB - The increase in fructose consumption is considered to be a risk factor for developing nonalcoholic fatty liver disease (NAFLD). We investigated the effects of docosahexaenoic acid (DHA) on hepatic lipid metabolism in fructose-treated primary mouse hepatocytes, and the changes of Endoplasmic reticulum (ER) stress pathways in response to DHA treatment. The hepatocytes were treated with fructose, DHA, fructose plus DHA, tunicamycin (TM) or fructose plus 4 phenylbutyric acid (PBA) for 24 h. Intracellular triglyceride (TG) accumulation was assessed by Oil Red O staining. The mRNA expression levels and protein levels related to lipid metabolism and ER stress response were determined by real-time PCR and Western blot. Fructose treatment led to obvious TG accumulation in primary hepatocytes through increasing expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), two key enzymes in hepatic de novo lipogenesis. DHA ameliorates fructose-induced TG accumulation by upregulating the expression of carnitine palmitoyltransferase 1A (CPT-1alpha) and acyl-CoA oxidase 1 (ACOX1). DHA treatment or pretreatment with the ER stress inhibitor PBA significantly decreased TG accumulation and reduced the expression of glucose-regulated protein 78 (GRP78), total inositol-requiring kinase 1 (IRE1alpha) and p-IRE1alpha. The present results suggest that DHA protects against high fructose-induced hepatocellular lipid accumulation. The current findings also suggest that alleviating the ER stress response seems to play a role in the prevention of fructose-induced hepatic steatosis by DHA. PMID- 26805876 TI - Chicken Essence for Cognitive Function Improvement: A Systematic Review and Meta Analysis. AB - Chicken essence (CE) is a popular traditional remedy in Asia, which is believed to improve cognitive functions. CE company claimed that the health benefits were proven with research studies. A systematic review was conducted to determine the cognitive-enhancing effects of CE. We systematically searched a number of databases for randomized controlled trials with human subjects consuming CE and cognitive tests involved. Cochrane's Risk of Bias (ROB) tool was used to assess the quality of trials and meta-analysis was performed. Seven trials were included, where six healthy subjects and one subject with poorer cognitive functions were recruited. One trial had unclear ROB while the rest had high ROB. For executive function tests, there was a significant difference favoring CE (pooled standardized mean difference (SMD) of -0.55 (-1.04, -0.06)) and another with no significant difference (pooled SMD of 0.70 (-0.001, 1.40)). For short term memory tests, no significant difference was found (pooled SMD of 0.63 ( 0.16, 1.42)). Currently, there is a lack of convincing evidence to show a cognitive enhancing effect of CE. PMID- 26805877 TI - Fish, Long-Chain n-3 PUFA and Incidence of Elevated Blood Pressure: A Meta Analysis of Prospective Cohort Studies. AB - Results from prospective cohort studies on fish or long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) intake and elevated blood pressure (EBP) are inconsistent. We aimed to investigate the summary effects. Pertinent studies were identified from PubMed and EMBASE database through October 2015. Multivariate adjusted risk ratios (RRs) for incidence of EBP in the highest verses the bottom category of baseline intake of fish or LC n-3 PUFA were pooled using a random effects meta-analysis. Over the follow-up ranging from 3 to 20 years, 20,497 EBP events occurred among 56,204 adults from eight prospective cohort studies. The summary RR (SRR) was 0.96 (95% CI: 0.81, 1.14; I2 = 44.70%) for fish in four studies, and 0.73 (95% CI: 0.60, 0.89; I2 = 75.00%) for LC n-3 PUFA in six studies (three studies for biomarker vs. three studies for diet). Circulating LC n-3 PUFA as biomarker was inversely associated with incidence of EBP (SRR: 0.67; 95% CI: 0.55, 0.83), especially docosahexaenoic acid (SRR: 0.64; 95% CI: 0.45, 0.88), whereas no significant association was found for dietary intake (SRR: 0.80; 95% CI: 0.58, 1.10). The present finding suggests that increased intake of docosahexaenoic acid to improve its circulating levels may benefit primary prevention of EBP. PMID- 26805875 TI - Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis. AB - The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. Manipulation of tryptophan levels, acutely or chronically, by depletion or supplementation, is an experimental procedure for modifying peripheral and central serotonin levels. These studies have allowed us to establish the role of serotonin in higher order brain function in both preclinical and clinical situations and have precipitated the finding that low brain serotonin levels are associated with poor memory and depressed mood. The gut-brain axis is a bi directional system between the brain and gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. An influence of gut microbiota on behaviour is becoming increasingly evident, as is the extension to tryptophan and serotonin, producing a possibility that alterations in the gut may be important in the pathophysiology of human central nervous system disorders. In this review we will discuss the effect of manipulating tryptophan on mood and cognition, and discuss a possible influence of the gut-brain axis. PMID- 26805878 TI - Effect of Cudrania tricuspidata and Kaempferol in Endoplasmic Reticulum Stress Induced Inflammation and Hepatic Insulin Resistance in HepG2 Cells. AB - In this study, we quantitated kaempferol in water extract from Cudrania tricuspidata leaves (CTL) and investigated its effects on endoplasmic reticulum (ER) stress-induced inflammation and insulin resistance in HepG2 cells. The concentration of kaempferol in the CTL was 5.07 +/- 0.08 mg/g. The HepG2 cells were treated with 300 ug/mL of CTL, 500 ug/mL of CTL, 1.5 ug/mL of kaempferol or 2.5 ug/mL of kaempferol, followed immediately by stimulation with 100 nM of thapsigargin for ER stress induction for 24 h. There was a marked increase in the activation of the ER stress and inflammation response in the thapsigargin stimulated control group. The CTL treatment interrupted the ER stress response and ER stress-induced inflammation. Kaempferol partially inhibited the ER stress response and inflammation. There was a significant increase in serine phosphorylation of insulin receptor substrate (IRS)-1 and the expression of C/EBPalpha and gluconeogenic genes in the thapsigargin-stimulated control group compared to the normal control. Both CTL and kaempferol suppressed serine phosphorylation of IRS-1, and the treatments did not interrupt the C/EBPalpha/gluconeogenic gene pathway. These results suggest that kaempferol might be the active compound of CTL and that it might protect against ER stress induced inflammation and hyperglycemia. PMID- 26805879 TI - Korean Pine Nut Oil Attenuated Hepatic Triacylglycerol Accumulation in High-Fat Diet-Induced Obese Mice. AB - Korean pine nut oil (PNO) has been reported to influence weight gain and lipid metabolism. We examined whether PNO replacement in a high-fat diet (HFD) can ameliorate HFD-induced hepatic steatosis. Five-week-old male C57BL mice were fed control diets containing 10% of the energy from fat from PNO or soybean oil (SBO) (PC, SC) or HFDs with 45% of the energy from fat, with 10% from PNO or SBO and 35% from lard (PHFD, SHFD), for 12 weeks. Body weight gain and amount of white adipose tissue were lower in PHFD (10% and 18% lower, respectively) compared with SHFD. Hepatic triacylglycerol (TG) level was significantly lower in PHFD than the SHFD (26% lower). PNO consumption upregulated hepatic ACADL mRNA levels. The hepatic PPARG mRNA level was lower in the PC than in the SC. Expression of the sirtuin (SIRT) 3 protein in white adipose tissue was down-regulated in the SHFD and restored in the PHFD to the level in the lean control mice. SIRT 3 was reported to be upregulated under conditions of caloric restriction (CR) and plays a role in regulating mitochondrial function. PNO consumption resulted in lower body fat and hepatic TG accumulation in HFD-induced obesity, which seemed to be associated with the CR-mimetic response. PMID- 26805880 TI - Dietary Changes over 25 Years in Tianjin Residents: Findings from the 1986-1988, 2000-2004, and 2008-2011 Nutrition Surveys. AB - In China, the rates of chronic diseases characteristic of countries in nutritional transition have been increasing. However, few studies have examined diet changes in recent decades. We analyzed dietary changes in Tianjin, China. The data in this descriptive, population-based study in >=18-year-old adults were collected from three surveys from 1986 to 2011. Food consumption and nutrient intake were compared among the three surveys separately for urban and rural areas. Differences in food consumption between urban and rural areas in different periods were also shown. The consumption of cereals, vegetables, and oils decreased, and that of fruits and beans increased in both urban and rural areas. Moreover, the total consumption of animal foods, especially milk, increased (0.01% in 1986-1988; 1.72% in 2008-2011) in rural areas. Although milk consumption also increased in urban areas, consumption of other animal foods decreased (19.33% in 1986-1988; 13.74% in 2008-2011). Meanwhile, cereals consumption rebounded from 22.63% in 2000-2004 to 29.75% in 2008-2011. Moreover, the lack of dairy products and some nutrients, e.g., retinol, calcium, and dietary fiber (<80% of recommended nutrient intake), in the diet persisted in both urban and rural areas. In conclusion, differences in diet between urban and rural areas decreased over time. PMID- 26805881 TI - Recombinant HSA-CMG2 Is a Promising Anthrax Toxin Inhibitor. AB - Anthrax toxin is the major virulence factor produced by Bacillus anthracis. Protective antigen (PA) is the key component of the toxin and has been confirmed as the main target for the development of toxin inhibitors. The inhibition of the binding of PA to its receptor, capillary morphogenesis protein-2 (CMG2), can effectively block anthrax intoxication. The recombinant, soluble von Willebrand factor type A (vWA) domain of CMG2 (sCMG2) has demonstrated potency against anthrax toxin. However, the short half-life of sCMG2 in vivo is a disadvantage for its development as a new anthrax drug. In the present study, we report that HSA-CMG2, a protein combining human serum albumin (HSA) and sCMG2, produced in the Pichia pastoris expression system prolonged the half-life of sCMG2 while maintaining PA binding ability. The IC50 of HSA-CMG2 is similar to those of sCMG2 and CMG2-Fc in in vitro toxin neutralization assays, and HSA-CMG2 completely protects rats from lethal doses of anthrax toxin challenge; these same challenge doses exceed sCMG2 at a sub-equivalent dose ratio and overwhelm CMG2-Fc. Our results suggest that HSA-CMG2 is a promising inhibitor of anthrax toxin and may contribute to the development of novel anthrax drugs. PMID- 26805883 TI - The Master Transcription Factor mtfA Governs Aflatoxin Production, Morphological Development and Pathogenicity in the Fungus Aspergillus flavus. AB - Aspergillus flavus produces a variety of toxic secondary metabolites; among them, the aflatoxins (AFs) are the most well known. These compounds are highly mutagenic and carcinogenic, particularly AFB1. A. flavus is capable of colonizing a number of economically-important crops, such as corn, cotton, peanut and tree nuts, and contaminating them with AFs. Molecular genetic studies in A. flavus could identify novel gene targets for use in strategies to reduce AF contamination and its adverse impact on food and feed supplies worldwide. In the current study, we investigated the role of the master transcription factor gene mtfA in A. flavus. Our results revealed that forced overexpression of mtfA results in a drastic decrease or elimination of several secondary metabolites, among them AFB1. The reduction in AFB1 was accompanied by a decrease in aflR expression. Furthermore, mtfA also regulates development; conidiation was influenced differently by this gene depending on the type of colonized substrate. In addition to its effect on conidiation, mtfA is necessary for the normal maturation of sclerotia. Importantly, mtfA positively affects the pathogenicity of A. flavus when colonizing peanut seeds. AF production in colonized seeds was decreased in the deletion mtfA strain and particularly in the overexpression strain, where only trace amounts were detected. Interestingly, a more rapid colonization of the seed tissue occurred when mtfA was overexpressed, coinciding with an increase in lipase activity and faster maceration of the oily part of the seed. PMID- 26805882 TI - The Biochemical Toxin Arsenal from Ant Venoms. AB - Ants (Formicidae) represent a taxonomically diverse group of hymenopterans with over 13,000 extant species, the majority of which inject or spray secretions from a venom gland. The evolutionary success of ants is mostly due to their unique eusociality that has permitted them to develop complex collaborative strategies, partly involving their venom secretions, to defend their nest against predators, microbial pathogens, ant competitors, and to hunt prey. Activities of ant venom include paralytic, cytolytic, haemolytic, allergenic, pro-inflammatory, insecticidal, antimicrobial, and pain-producing pharmacologic activities, while non-toxic functions include roles in chemical communication involving trail and sex pheromones, deterrents, and aggregators. While these diverse activities in ant venoms have until now been largely understudied due to the small venom yield from ants, modern analytical and venomic techniques are beginning to reveal the diversity of toxin structure and function. As such, ant venoms are distinct from other venomous animals, not only rich in linear, dimeric and disulfide-bonded peptides and bioactive proteins, but also other volatile and non-volatile compounds such as alkaloids and hydrocarbons. The present review details the unique structures and pharmacologies of known ant venom proteinaceous and alkaloidal toxins and their potential as a source of novel bioinsecticides and therapeutic agents. PMID- 26805884 TI - Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice. AB - Oxaliplatin, a chemotherapeutic drug for colorectal cancer, induces severe peripheral neuropathy. Bee venom acupuncture (BVA) has been used to attenuate pain, and its effect is known to be mediated by spinal noradrenergic and serotonergic receptors. Morphine is a well-known opioid used to treat different types of pain. Here, we investigated whether treatment with a combination of these two agents has an additive effect on oxaliplatin-induced neuropathic pain in mice. To assess cold and mechanical allodynia, acetone and von Frey filament tests were used, respectively. Significant allodynia signs were observed three days after an oxaliplatin injection (6 mg/kg, i.p.). BVA (0.25, 1, and 2.5 mg/kg, s.c., ST36) or morphine (0.5, 2, and 5 mg/kg, i.p.) alone showed dose-dependent anti-allodynic effects. The combination of BVA and morphine at intermediate doses showed a greater and longer effect than either BVA or morphine alone at the highest dose. Intrathecal pretreatment with the opioidergic (naloxone, 20 MUg) or 5-HT3 (MDL-72222, 15 MUg) receptor antagonist, but not with alpha2 adrenergic (idazoxan, 10 MUg) receptor antagonist, blocked this additive effect. Therefore, we suggest that the combination effect of BVA and morphine is mediated by spinal opioidergic and 5-HT3 receptors and this combination has a robust and enduring analgesic action against oxaliplatin-induced neuropathic pain. PMID- 26805885 TI - Differential Properties of Venom Peptides and Proteins in Solitary vs. Social Hunting Wasps. AB - The primary functions of venoms from solitary and social wasps are different. Whereas most solitary wasps sting their prey to paralyze and preserve it, without killing, as the provisions for their progeny, social wasps usually sting to defend their colonies from vertebrate predators. Such distinctive venom properties of solitary and social wasps suggest that the main venom components are likely to be different depending on the wasps' sociality. The present paper reviews venom components and properties of the Aculeata hunting wasps, with a particular emphasis on the comparative aspects of venom compositions and properties between solitary and social wasps. Common components in both solitary and social wasp venoms include hyaluronidase, phospholipase A2, metalloendopeptidase, etc. Although it has been expected that more diverse bioactive components with the functions of prey inactivation and physiology manipulation are present in solitary wasps, available studies on venom compositions of solitary wasps are simply too scarce to generalize this notion. Nevertheless, some neurotoxic peptides (e.g., pompilidotoxin and dendrotoxin-like peptide) and proteins (e.g., insulin-like peptide binding protein) appear to be specific to solitary wasp venom. In contrast, several proteins, such as venom allergen 5 protein, venom acid phosphatase, and various phospholipases, appear to be relatively more specific to social wasp venom. Finally, putative functions of main venom components and their application are also discussed. PMID- 26805886 TI - Roles of Anthrax Toxin Receptor 2 in Anthrax Toxin Membrane Insertion and Pore Formation. AB - Interaction between bacterial toxins and cellular surface receptors is an important component of the host-pathogen interaction. Anthrax toxin protective antigen (PA) binds to the cell surface receptor, enters the cell through receptor mediated endocytosis, and forms a pore on the endosomal membrane that translocates toxin enzymes into the cytosol of the host cell. As the major receptor for anthrax toxin in vivo, anthrax toxin receptor 2 (ANTXR2) plays an essential role in anthrax toxin action by providing the toxin with a high affinity binding anchor on the cell membrane and a path of entry into the host cell. ANTXR2 also acts as a molecular clamp by shifting the pH threshold of PA pore formation to a more acidic pH range, which prevents premature pore formation at neutral pH before the toxin reaches the designated intracellular location. Most recent studies have suggested that the disulfide bond in the immunoglobulin (Ig)-like domain of ANTXR2 plays an essential role in anthrax toxin action. Here we will review the roles of ANTXR2 in anthrax toxin action, with an emphasis on newly updated knowledge. PMID- 26805887 TI - The Role of G-Protein-Coupled Receptor Proteolysis Site Cleavage of Polycystin-1 in Renal Physiology and Polycystic Kidney Disease. AB - Polycystin-1 (PC1) plays an essential role in renal tubular morphogenesis, and PC1 dysfunction causes human autosomal dominant polycystic kidney disease. A fundamental characteristic of PC1 is post-translational modification via cleavage at the juxtamembrane GPCR proteolysis site (GPS) motif that is part of the larger GAIN domain. Given the considerable biochemical complexity of PC1 molecules generated in vivo by this process, GPS cleavage has several profound implications on the intracellular trafficking and localization in association with their particular function. The critical nature of GPS cleavage is further emphasized by the increasing numbers of PKD1 mutations that significantly affect this cleavage process. The GAIN domain with the GPS motif therefore represents the key structural element with fundamental importance for PC1 and might be polycystic kidney disease's (PKD) Achilles' heel in a large spectrum of PKD1 missense mutations. We highlight the central roles of PC1 cleavage for the regulation of its biogenesis, intracellular trafficking and function, as well as its significance in polycystic kidney disease. PMID- 26805888 TI - Expression Profiles and Biological Roles of miR-196a in Swine. AB - MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, which play important roles in animals by targeting mRNA transcripts for translational repression. Recent studies have demonstrated that miRNAs are involved in regulation of adipocyte development. The expression of miR-196a in different porcine tissues and developing fat tissues was detected, and gene ontology (GO) term enrichment was then used to predict the expression profiles and potential biological roles of miR-196a in swine. To further verify the roles of miR-196a in porcine adipocyte development, a recombinant adenovirus encoding miR-196a gene (Ad-miR-196a) was constructed and used to study the effect of miR-196a on preadipocyte proliferation and differentiation. Here, our data demonstrate that miR-196a displays a tissue-specific expression pattern and has comprehensive biological roles in swine, especially in adipose development. In addition, overexpression of miR-196a had no effect on preadipocyte proliferation, but induced preadipocyte differentiation by increasing expression of adipocyte specific markers, lipid accumulation and triglyceride content. These data represent the first demonstration of miR-196a expression profiles and roles in swine, thereby providing valuable insight into the functions of miR-196a in adipocyte biology. PMID- 26805889 TI - Genetics of Congenital Heart Defects: The NKX2-5 Gene, a Key Player. AB - Congenital heart defects (CHDs) represent the biggest fraction of morbid congenital anomalies worldwide. Owing to their complex inheritance patterns and multifactorial etiologies, these defects are difficult to identify before complete manifestation. Research over the past two decades has established firmly the role of genetics in the development of these congenital defects. While syndromic CHDs are more straightforward, non-syndromic CHDs are usually characterized by multiple mutations that affect intricate inter-connected developmental pathways. Knock-out and gene expression studies in mice and other genetic models have been performed to elucidate the roles of these implicated genes. Functional analysis has not been able to resolve the complete picture, as increasingly more downstream effects are continuously being assigned to CHD mutant factors. NKX2-5, a cardiac transcription factor, has received much attention for its role in cardiac dysmorphogenesis. Approximately 50 different mutations in this gene have been identified to date, and only a few have been functionally characterized. The mutant NKX2-5 factor can regulate a number of off targets downstream to facilitate CHD development. This review summarizes the genetic etiology of congenital heart defects and emphasizes the need for NKX2-5 mutation screening. PMID- 26805890 TI - Information Technology Support for Clinical Genetic Testing within an Academic Medical Center. AB - Academic medical centers require many interconnected systems to fully support genetic testing processes. We provide an overview of the end-to-end support that has been established surrounding a genetic testing laboratory within our environment, including both laboratory and clinician facing infrastructure. We explain key functions that we have found useful in the supporting systems. We also consider ways that this infrastructure could be enhanced to enable deeper assessment of genetic test results in both the laboratory and clinic. PMID- 26805891 TI - An eMERGE Clinical Center at Partners Personalized Medicine. AB - The integration of electronic medical records (EMRs) and genomic research has become a major component of efforts to advance personalized and precision medicine. The Electronic Medical Records and Genomics (eMERGE) network, initiated in 2007, is an NIH-funded consortium devoted to genomic discovery and implementation research by leveraging biorepositories linked to EMRs. In its most recent phase, eMERGE III, the network is focused on facilitating implementation of genomic medicine by detecting and disclosing rare pathogenic variants in clinically relevant genes. Partners Personalized Medicine (PPM) is a center dedicated to translating personalized medicine into clinical practice within Partners HealthCare. One component of the PPM is the Partners Healthcare Biobank, a biorepository comprising broadly consented DNA samples linked to the Partners longitudinal EMR. In 2015, PPM joined the eMERGE Phase III network. Here we describe the elements of the eMERGE clinical center at PPM, including plans for genomic discovery using EMR phenotypes, evaluation of rare variant penetrance and pleiotropy, and a novel randomized trial of the impact of returning genetic results to patients and clinicians. PMID- 26805892 TI - The Information Technology Infrastructure for the Translational Genomics Core and the Partners Biobank at Partners Personalized Medicine. AB - The Biobank and Translational Genomics core at Partners Personalized Medicine requires robust software and hardware. This Information Technology (IT) infrastructure enables the storage and transfer of large amounts of data, drives efficiencies in the laboratory, maintains data integrity from the time of consent to the time that genomic data is distributed for research, and enables the management of complex genetic data. Here, we describe the functional components of the research IT infrastructure at Partners Personalized Medicine and how they integrate with existing clinical and research systems, review some of the ways in which this IT infrastructure maintains data integrity and security, and discuss some of the challenges inherent to building and maintaining such infrastructure. PMID- 26805893 TI - Oviposition by Female Plodia interpunctella (Lepidoptera: Pyralidae): Description and Time Budget Analysis of Behaviors in Laboratory Studies. AB - The oviposition behavior of the Indian meal moth, Plodia interpunctella (Hubner) (Lepidoptera: Pyralidae), a major insect pest of durable stored foods, was studied in small experimental arenas under laboratory conditions using videography, and a time budget analysis of its behaviors was documented. Resting gravid females typically became active shortly after the start of the scotophase. The characteristic behaviors exhibited by mated females prior to oviposition included antennal movement, grooming of antennae and mouth parts using the forelegs, walking or flying, and abdomen bending and dragging. Pre-oviposition behaviors such as antennal grooming and walking or flying were observed to alternate several times before females commenced the abdominal dragging behavior that preceded egg laying. Eggs were laid singly or sometimes in groups, either freely or stuck to food material. Gravid females showed little or no movement during the photophase; however, they actively flew and oviposited during the scotophase. Females allocated only a small portion of their time to oviposition while the rest of the time was spent away from food. Females oviposited on food material by making repeated visits, predominantly during the first four hours of the scotophase. Visits and time spent on food declined as the scotophase advanced. PMID- 26805894 TI - Effects of Antioxidants in Human Cancers: Differential Effects on Non-Coding Intronic RNA Expression. AB - The notion that dietary antioxidants can help fight cancer is popular. However, the mechanism(s) behind the effect of antioxidants in cancer is still unclear. Previous studies indicate that supplements can influence gene expression; however, all of these studies were focused on the coding/exonic gene expression. Studies are now emerging to highlight critical functional roles for RNAs expressed from the non-coding regions. This project was designed to study the effect of antioxidant supplements on non-coding intronic RNA expression in human cancers. Vitamin E, N-Acetyl cysteine (NAC) and Sulforaphane are commonly used supplements to prevent diseases including cancers. We studied the effect of these antioxidant supplements on the non-coding intronic RNA expression using publicly available datasets from a mouse model for lung cancer and prostate cancer cell lines. Although high throughput polyA-enriched RNA-Seq data characterize spliced coding mRNA regions, recent studies reveal the expression of reads from the non coding intronic regions. Our analyses indicate that cancer cells have higher expression of introns compared to that of normal cells and that treatment with antioxidant supplements reduces the increased expression of introns of several genes. However, we did find high expression of introns of multiple genes including many oncogenes in the supplement treated groups compared to that of the control; this effect was distinct depending on the cell type and the supplement studied. Using RT-PCRs, we validated the expression of introns of two oncogenes, DLK1 and LRG1, known to be key players in lung cancer progression, and demonstrate changed intronic expression with supplement treatment in cancer cells. With regard to the antioxidant system, supplements did not change the intronic RNAs for endogenous antioxidant enzymes except for a significant decrease in the expression of superoxide dismutase (SOD) intronic RNA. Concurrently, we also found that a prolonged (48 h) exposure to Vitamin C, Vitamin E and Green tea extract reduced the enzymatic activity of SOD in lung cancer cells. The results from this study reveal that the antioxidant supplements have a significant effect on the intronic RNA expression of many genes including cancer genes that are not directly linked to the body's antioxidant system. It is important to study this novel effect of antioxidant supplements in detail as it may have a significant role in disease progression. PMID- 26805895 TI - Lactation Affects Isolated Mitochondria and Its Fatty Acid Composition but Has No Effect on Tissue Protein Oxidation, Lipid Peroxidation or DNA-Damage in Laboratory Mice. AB - Linking peak energy metabolism to lifespan and aging remains a major question especially when focusing on lactation in females. We studied, if and how lactation affects in vitro mitochondrial oxygen consumption and mitochondrial fatty acid composition. In addition, we assessed DNA damage, lipid peroxidation and protein carbonyls to extrapolate on oxidative stress in mothers. As model system we used C57BL/6NCrl mice and exposed lactating females to two ambient temperatures (15 degrees C and 22 degrees C) while they nursed their offspring until weaning. We found that state II and state IV respiration rates of liver mitochondria were significantly higher in the lactating animals than in non lactating mice. Fatty acid composition of isolated liver and heart mitochondria differed between lactating and non-lactating mice with higher n-6, and lower n-3 polyunsaturated fatty acids in the lactating females. Surprisingly, lactation did not affect protein carbonyls, lipid peroxidation and DNA damage, nor did moderate cold exposure of 15 degrees C. We conclude that lactation increases rates of mitochondrial uncoupling and alters mitochondrial fatty acid composition thus supporting the "uncoupling to survive" hypothesis. Regarding oxidative stress, we found no impact of lactation and lower ambient temperature and contribute to growing evidence that there is no linear relationship between oxidative damage and lactation. PMID- 26805897 TI - Anti-IgE Qb-VLP Conjugate Vaccine Self-Adjuvants through Activation of TLR7. AB - Qb bacteriophage virus-like particles (Qb-VLP) are utilized as carriers to enhance immune responses to weakly or non-immunogenic antigens such as peptides and haptens. Qb-VLPs are formed through the self-assembly of multiple Qb capsid protein monomers, a process which traps a large amount of bacterial RNA in the core of the VLP. Bacterial RNA is known to activate the innate immune system via TLR 7 and 8 found within the endosomes of certain immune cells and has been shown to contribute to the immunogenicity of Qb-VLP vaccines. Herein, we evaluated an anti-IgE vaccine comprised of two IgE peptides (Y and P) conjugated to Qb-VLP (Qb Y and Qb-P, respectively) for in vitro stimulation of human PBMCs and in vivo immunogenicity in mice. The in vitro secretion of IFN-alpha from human PBMCs exposed to Qb-Y is consistent with TLR7 activation. Immunization of mice with the IgE peptide Qb-VLP conjugates induced high titers of anti-IgE antibodies in wild type mice, but significantly lower titers in TLR7 knockout mice, supporting the self-adjuvanting role of the RNA. Inclusion of alum and alum/CpG as adjuvants partially or completely compensated for the lack of TLR7 activation in TLR7 deficient mice. Our study demonstrates the key role that TLR7 plays in the immunogenicity of the IgE peptide Qb-VLP conjugate vaccine. PMID- 26805896 TI - Hydrogen Sulfide, Oxidative Stress and Periodontal Diseases: A Concise Review. AB - In the past years, biomedical research has recognized hydrogen sulfide (H2S) not only as an environmental pollutant but also, along with nitric oxide and carbon monoxide, as an important biological gastransmitter with paramount roles in health and disease. Current research focuses on several aspects of H2S biology such as the biochemical pathways that generate the compound and its functions in human pathology or drug synthesis that block or stimulate its biosynthesis. The present work addresses the knowledge we have to date on H2S production and its biological roles in the general human environment with a special focus on the oral cavity and its involvement in the initiation and development of periodontal diseases. PMID- 26805899 TI - Clarification of Orange Press Liquors by PVDF Hollow Fiber Membranes. AB - Press liquors are typical by-products of the citrus juice processing characterized by a high content of organic compounds and associated problems of environmental impact, which imply high treatment costs. However, these wastes contain a great number of health promoting substances, including fibers, carotenoids and phenolic compounds (mainly flavonoids), whose recovery against waste-destruction technologies is very attractive for new business opportunities. In this work, the clarification of orange press liquor by using microfiltration (MF) membranes is studied as a preliminary step to obtain a permeate stream enriched in antioxidant compounds which can be further processed to produce extracts of nutraceutical and/or pharmaceutical interest. MF poly(vinylidene fluoride) (PVDF) hollow fibers were prepared by the dry/wet spinning technique. A series of fibers was produced from the same polymeric dope, in order to investigate the effect of selected spinning parameters, i.e., bore fluid composition and flowrate, on their properties. The morphology of the produced fibers was analyzed by Scanning Electron Microscopy (SEM). Fibers were further characterized for their mechanical properties, porosity, bubble point, pore size distribution and pure water permeability (PWP). Some of the produced fibers exhibited high permeability (pure water permeability ~530 L/m2.h.bar), coupled to good mechanical resistance and pore size in the range of MF membranes. These fibers were selected and used for the clarification of press liquor from orange peel processing. In optimized operating conditions, the selected fibers produced steady-state fluxes of about 41 L/m2.h with rejections towards polyphenols and total antioxidant activity of 4.1% and 1.4%, respectively. PMID- 26805900 TI - Hemophilia in the 21st century: tremendous progress, tremendous opportunity. PMID- 26805898 TI - Current Advances in Virus-Like Particles as a Vaccination Approach against HIV Infection. AB - HIV-1 virus-like particles (VLPs) are promising vaccine candidates against HIV-1 infection. They are capable of preserving the native conformation of HIV-1 antigens and priming CD4+ and CD8+ T cell responses efficiently via cross presentation by both major histocompatibility complex (MHC) class I and II molecules. Progress has been achieved in the preclinical research of HIV-1 VLPs as prophylactic vaccines that induce broadly neutralizing antibodies and potent T cell responses. Moreover, the progress in HIV-1 dendritic cells (DC)-based immunotherapy provides us with a new vision for HIV-1 vaccine development. In this review, we describe updates from the past 5 years on the development of HIV 1 VLPs as a vaccine candidate and on the combined use of HIV particles with HIV-1 DC-based immunotherapy as efficient prophylactic and therapeutic vaccination strategies. PMID- 26805901 TI - Factor VIII/factor IX prophylaxis for severe hemophilia. AB - Experience with clotting factor concentrate (CFC) replacement products over several decades has shown that regular replacement (prophylaxis) is the only way to prevent musculoskeletal damage in hemophilia and impact the natural history of hemophilia. Yet there is a lack of data on the optimal age to start such replacement therapy and the regimens to be used. While very early administration of high doses is certainly more effective in preventing bleeding, cost and compliance are major constraints all over the world. Starting prophylaxis with even lower doses comparable to that used in episodic therapies leads to major reduction in bleeding. Recognition of the clinical heterogeneity of hemophilia even among patients with a label of severe hemophilia in terms of their spontaneous bleeding has led to efforts aimed at individualizing CFC replacement, based on clinical responses or pharmacokinetic data of the CFC. The importance of long-term outcome assessment being combined with CFC replacement therapy cannot be overemphasized. PMID- 26805903 TI - Advances in the clinical management of inhibitors in hemophilia A and B. AB - Inhibitors to factor (F)VIII or FIX are the most serious and challenging complication of hemophilia treatment, increasing morbidity and mortality because bleeds no longer respond to standard clotting factor replacement therapy. For patients with high-titer inhibitors, immune tolerance induction achieved through regular factor exposure is the only proven therapy capable of Inhibitor eradication and is almost always indicated for inhibitors of recent onset. Bypassing therapy is used to treat and prevent bleeding, but neither of the two currently available bypassing agents has the predictable hemostatic efficacy of factor replacement in hemophilia patients without inhibitors. Major research efforts are focused on the development of new, more potent therapies for the management of patients with inhibitors. PMID- 26805904 TI - Laboratory monitoring of new hemostatic agents for hemophilia. AB - Prophylactic infusion of factor replacement products results in a reduction in long-term morbidity and mortality in patients with severe hemophilia. However, intravenous access is commonly through central venous access devices, which may result in complications such as infections and thrombosis. Available clinical data on extended half-life (EHL) factor replacement products indicate the potential for a significant reduction in the need for frequent infusions, eg, once per week for factor (F)IX and twice per week for FVIII. With the current generation of factor replacement products, individualized pharmacokinetics (pK) direct optimal prophylactic dosing. The available data on the EHL factor replacement products also confirm similar individualized variability. Optimal dosing of these therapies relies on accurate assays, of which there is a variety, although performance characteristics vary with the specific product being tested. Herein, the data on clinical trials and laboratory assays are reviewed. PMID- 26805902 TI - Advances and challenges in hemophilic arthropathy. AB - Hemophilic arthropathy is a form of joint disease that develops secondary to joint bleeding and presents with synovial hypertrophy, cartilage and bony destruction. The arthropathy can develop despite clotting factor replacement and is especially disabling in the aging population. Pathobiological tissue changes are triggered by release of hemoglobin and iron deposition in the joint, but the sequence of events and the molecular mechanisms resulting in joint deterioration are incompletely understood. Treatment options other than clotting factor replacement are limited. Improvements in the treatment of hemophilia necessitate a better understanding of the processes that lead to this disabling condition and better diagnostic tools. Towards that end, studies of the molecular mechanisms leading to the arthropathy, as well as the development of sensitive imaging techniques and biomarkers are needed. These will pave the way to identify the cause of acute pain such as joint bleeding or synovitis, detect early, potentially reversible structural changes, and predict progression of disease. This review describes current imaging techniques and the development of high resolution musculoskeletal ultrasound with power Doppler to afford point-of-care diagnosis and management, the potential utility of diagnostic biomarkers, and summarizes our current knowledge of the pathobiology of hemophilic arthropathy. PMID- 26805905 TI - Aging among persons with hemophilia: contemporary concerns. AB - The life expectancy of persons with hemophilia (PWH) has increased almost 10-fold over the past seven decades, largely due to access to safe factor replacement products. Concomitant with this success, however, comes the burden of aging. Older PWH are developing similar comorbidities as the general population, including increasing rates of hypertension, obesity, and diabetes, which predispose them to chronic diseases such as cardiovascular disease (CVD) and chronic kidney disease (CKD). How their coagulopathy affects the expression of these conditions remains unclear. In addition, the elderly hemophilia population must cope with chronic joint arthropathy, which provokes falls and fractures, and complications related to human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections, which greatly impact the incidence of cancer and liver disease. With a dearth of evidence-based guidelines to direct therapy, a new challenge has arisen for hematologists to optimally manage these complex age-related issues. This review will focus on common complications affecting the older hemophilia population, including joint disease, CVD, malignancy, renal insufficiency, and liver disease. PMID- 26805906 TI - Global assays in hemophilia. AB - The quest for the ideal method to study hemostasis in the evaluation and management of patients with bleeding disorders such as hemophilia is an ongoing effort. With the rapid evolution of biotechnology and the emergence of several new products for treatment of patients with hemophilia with and without inhibitors, there is a great need for tests that can be used to reliably evaluate and monitor our interventions. Global assays in coagulation allow the study of the interaction between the components involved in the process of hemostasis and are therefore considered by many to be more reflective of the in vivo hemostatic mechanism. Here we provide a brief review of the most widely used global assays in hemostasis (thrombin generation and thromboelastography) and their utility in the evaluation and management of hemophilia. PMID- 26805907 TI - Gene therapy for hemophilia: past, present and future. AB - After numerous preclinical studies demonstrated consistent success in large and small animal models, gene therapy has finally seen initial signs of clinically meaningful success. In a landmark study, Nathwani and colleagues reported sustained factor (F)IX expression in individuals with severe hemophilia B following adeno-associated virus (AAV)-mediated in vivo FIX gene transfer. As the next possible treatment-changing paradigm in hemophilia care, gene therapy may provide patients with sufficient hemostatic improvement to achieve the World Federation of Hemophilia's aspirational goal of "integration of opportunities in all aspects of life... equivalent to someone without a bleeding disorder." Although promising momentum supports the potential of gene therapy to replace protein-based therapeutics for hemophilia, several obstacles remain. The largest challenges appear to be overcoming the cellular immune responses to the AAV capsid; preexisting AAV neutralizing antibodies, which immediately exclude approximately 50% of the target population; and the ability to scale-up vector manufacturing for widespread applicability. Additional obstacles specific to hemophilia A (HA) include designing a vector cassette to accommodate a larger cDNA; avoiding development of inhibitory antibodies; and, perhaps the greatest difficulty to overcome, ensuring adequate expression efficiency. This review discusses the relevance of gene therapy to the hemophilia disease state, previous research progress, the current landscape of clinical trials, and considerations for promoting the future availability of gene therapy for hemophilia. PMID- 26805909 TI - The Effects of Combination of Robot-Assisted Therapy With Task-Specific or Impairment-Oriented Training on Motor Function and Quality of Life in Chronic Stroke. AB - BACKGROUND: Robot-assisted therapy (RT) is a promising intervention for stroke rehabilitation. RT hybridized with therapist-mediated therapy (eg, RT plus task specific or impairment-oriented training) may possibly yield functionally relevant improvements. A comparative study of the different combination regimens is needed. OBJECTIVE: To investigate the efficacy of RT combined with task specific training or impairment-oriented training on motor function and quality of life in patients with chronic stroke. DESIGN: A single-blind, randomized comparative efficacy study. SETTING: Two medical centers in Taiwan. PARTICIPANTS: Twenty-one subjects with chronic stroke. INTERVENTIONS: Participants were recruited and randomized into 1 of 2 groups: (1) RT combined with task-specific (RTT) training (enrolled, n = 11; completed, n = 11) or (2) RT combined with impairment-oriented (RTI) training (enrolled, n = 10; completed, n = 9). Participants received 20 intervention sessions (90-100 min/d, 5 d/wk for 4 weeks). OUTCOMES: The Fugl-Meyer Motor Assessment Upper Extremity subscale, Stroke Impact Scale, Action Research Arm Test, and Medical Research Council Scale were administered at baseline, posttreatment, and at 3-month follow-up. Two-way repeated-measures analysis of variance was used to investigate the treatment effects. RESULTS: The improvements of the RTT group in motor function measured by the Fugl-Meyer Motor Assessment Upper Extremity subscale and quality of life assessed by the Stroke Impact Scale were significantly superior to the RTI group after the interventions. The improvements of the RTT group were maintained for 3 months. Both groups demonstrated significant within-group improvements in motor function, muscle power, and quality of life. CONCLUSIONS: RTT may be a more compelling approach to enhance motor function and quality of life for a long-term period than RTI. The combination of RT with task-specific training and with impairment-oriented training had similar benefits on upper limb motor function and muscle strength immediately after the interventions. PMID- 26805910 TI - Presentation and Rehabilitation in a Patient With Toxoplasmosis Encephalitis: A Case Study and Review. AB - Toxoplasma gondii is an opportunistic infection that often presents in the setting of acquired immunodeficiency syndrome. The infection can cause severe and potentially fatal encephalitis because of the reactivation of latent infections in the setting of immune suppression. Diagnosing toxoplasmosis encephalitis (TE) in immunocompromised patients often is difficult because the signs and symptoms can be nonspecific, but making a diagnosis of TE is even more challenging in a patient who is not known to have human immunodeficiency virus/acquired immunodeficiency syndrome and shows no other signs of being immunocompromised. Early diagnosis and treatment can result in rapid radiologic and clinical improvement; however, no studies exist that evaluate the utility of functional rehabilitation for patients diagnosed with TE. Although previous studies report a good prognosis for patients who receive antibiotic treatment, they do not discuss the extent to which functional abilities lost during the infection are returned after their treatment. We discuss a case of stroke-like presentation of cerebral TE in a patient whose human immunodeficiency virus status was previously unknown and report the functional improvements that were made during acute inpatient rehabilitation. PMID- 26805908 TI - The Relationship Among Neuromuscular Impairments, Chronic Back Pain, and Mobility in Older Adults. AB - BACKGROUND: For older adults with mobility problems, one focus of rehabilitation is treating the underlying neuromuscular impairment(s) that lead to functional decline and disability. Knowing which neuromuscular impairments contribute to basic mobility tasks among older adults with back pain will fill an important knowledge gap and is a critical step towards developing mechanistically based rehabilitative interventions. OBJECTIVE: To evaluate the relationship of neuromuscular impairments with performance of mobility tasks among older adults with and without back pain. DESIGN: Cross-sectional analysis of baseline data from the Boston Rehabilitative Impairment Study of the Elderly. SETTING: Primary care-based population. PATIENTS: Participants (N = 430) were older primary care patients who completed assessments of neuromuscular impairments and mobility tasks. METHODS: Back pain was assessed by the use of an established comorbidity questionnaire. Neuromuscular impairments included trunk extensor muscle endurance, kyphosis, leg strength, leg strength asymmetry, leg speed, mean reaction time, leg coordination, and knee and ankle range of motion. MAIN OUTCOME MEASUREMENTS: Mobility tasks included gait speed, standing balance, chair stand, and patient-reported functional status. Analysis of covariance was used to generate adjusted means for neuromuscular impairments that differed significantly by back pain status. Separate multivariable regression models evaluated the association between neuromuscular impairments and mobility based on back pain status after we adjusted for sociodemographic factors and physiologic impairments. RESULTS: Participants had an average age of 77 years, 68% were female, and 31% reported back pain. Trunk extensor muscle endurance, leg strength, and rapid leg coordination were significantly lower among those with back pain compared to those without (P < .01, P = .01, P = .04, respectively). Patterns of neuromuscular impairments that were associated with mobility tasks differed according to back pain status. CONCLUSIONS: The neuromuscular impairment profiles associated with mobility function among older adults with back pain vary compared with older adults without back pain. PMID- 26805911 TI - Radioactive Doses - Predicted and Actual - and Likely Health Effects. AB - Five years have passed since the nuclear accident at Fukushima Daiichi Nuclear Power Stations on 11 March 2011. Here we refer to reports from international organisations as sources of predicted values obtained from environmental monitoring and dose estimation models, and reports from various institutes in Japan are used as sources of individual actual values. The World Health Organization, based on information available up to 11 September 2011 (and published in 2012), reported that characteristic effective doses in the first year after the accident, to all age groups, were estimated to be in the 10-50 mSv dose band in example locations in evacuation areas. Estimated characteristic thyroid doses to infants in Namie Town were within the 100-200 mSv dose band. A report from the United Nations Scientific Committee on the Effects of Atomic Radiation published in 2014 shows that the effective dose received by adults in evacuation areas during the first year after the accident was 1.1-13 mSv. The absorbed dose to the thyroid in evacuated settlements was 7.2-35 mSv in adults and 15-83 mSv in 1-year-old infants. Individual external radiation exposure in the initial 4 months after the accident, estimated by superimposing individual behaviour data on to a daily dose rate map, was less than 3 mSv in 93.9% of residents (maximum 15 mSv) in evacuation areas. Actual individual thyroid equivalent doses were less than 15 mSv in 98.8% of children (maximum 25 mSv) in evacuation areas. When uncertainty exists in dose estimation models, it may be sensible to err on the side of caution, and final estimated doses are often much greater than actual radiation doses. However, overestimation of the dose at the time of an accident has a great influence on the psychology of residents. More than 100 000 residents have not returned to the evacuation areas 5 years after the Fukushima accident because of the social and mental effects during the initial period of the disaster. Estimates of radiation doses placed in the public domain must be based on scientific evidence, and the way such information is communicated to residents should be carefully considered to avoid psychosocial effects that may have a greater bearing on health than the radiation itself. PMID- 26805912 TI - Resonant X-ray emission spectroscopy of platinum(II) anticancer complexes. AB - Platinum-based drugs are commonly used in cancer treatment. The biological activity of a metallodrug is obviously closely related to its chemical and stereochemical characteristics. An overlooked aspect is the effect of the ligand to the electronic structure of the metal atom (coordinated atom). We report herein a Resonant X-ray Emission Spectroscopy (RXES) study on the chemical speciation of chiral platinum complexes in which diastereomers are distinguished on the basis of their metal electronic configuration. This demonstrates RXES high chemical speciation capabilities, a necessary property to further investigate the reactivity of the Pt atom towards nucleophiles or bionucleophiles, and an important complement the previously reported RXES abilities, namely that it can be employed for in situ studies at physiological concentrations. PMID- 26805913 TI - [Long-term treatment of lower urinary tract symptoms in elderly]. PMID- 26805914 TI - [Varenicline in nicotine replacement therapy: Does it really increase the risk of cardiovascular and neuropsychiatric events?]. PMID- 26805915 TI - [Efficacy and safety of early mobilisation after stroke onset (AVERT): A randomised controlled trial]. PMID- 26805916 TI - In vivo characterization of ischemic small intestine using bioimpedance measurements. AB - The standard clinical method for the assessment of viability in ischemic small intestine is still visual inspection and palpation. This method is non-specific and unreliable, and requires a high level of clinical experience. Consequently, viable tissue might be removed, or irreversibly damaged tissue might be left in the body, which may both slow down patient recovery. Impedance spectroscopy has been used to measure changes in electrical parameters during ischemia in various tissues. The physical changes in the tissue at the cellular and structural levels after the onset of ischemia lead to time-variant changes in the electrical properties. We aimed to investigate the use of bioimpedance measurement to assess if the tissue is ischemic, and to assess the ischemic time duration. Measurements were performed on pigs (n = 7) using a novel two-electrode setup, with a Solartron 1260/1294 impedance gain-phase analyser. After induction of anaesthesia, an ischemic model with warm, full mesenteric arterial and venous occlusion on 30 cm of the jejunum was implemented. Electrodes were placed on the serosal surface of the ischemic jejunum, applying a constant voltage, and measuring the resulting electrical admittance. As a control, measurements were done on a fully perfused part of the jejunum in the same porcine model. The changes in tan delta (dielectric parameter), measured within a 6 h period of warm, full mesenteric occlusion ischemia in seven pigs, correlates with the onset and duration of ischemia. Tan delta measured in the ischemic part of the jejunum differed significantly from the control tissue, allowing us to determine if the tissue was ischemic or not (P < 0.0001, F = (1,75.13) 188.19). We also found that we could use tan delta to predict ischemic duration. This opens up the possibility of real-time monitoring and assessment of the presence and duration of small intestinal ischemia. PMID- 26805917 TI - Development of a Severe Mitral Valve Stenosis Secondary to the Treatment of Mitral Regurgitation with a Single MitraClip. AB - We report a patient with class III heart failure symptoms due to mitral regurgitation (MR) subsequent to nonischemic cardiomyopathy. The patient underwent percutaneous transcatheter mitral valve repair using a single MitraClip, which reduced the MR; however it created mild-to-moderate mitral stenosis, which progressed to severe mitral stenosis. Subsequently the patient underwent mitral valve replacement surgery. PMID- 26805918 TI - Mepiquat: A Process-Induced Byproduct in Roasted Cereal-Based Foodstuffs. AB - Mepiquat, a growth regulator widely used in agriculture, is also known as a process-induced byproduct formed in coffee from natural constituents during heat treatments such as roasting. This study examines mepiquat formation in cereal based foodstuffs treated at sufficiently high temperature to trigger methyl transfer reactions that involve glycine betaine and choline naturally present in cereals. Color measurements of roasted barley grains revealed a correlation between thermal treatment and mepiquat content. Trials at industrial scale on instant beverages composed of roasted cereals demonstrated significant increases in mepiquat during the thermal process (in the range of 140-205 MUg/kg in final products). A targeted survey of commercial products showed mepiquat in the range 69-381 MUg/kg in powdered cereal instant drinks and 42-168 MUg/kg in mugicha tea, a roasted barley infusion. These findings will not significantly affect the exposure of consumers to mepiquat due to the low amounts detected. PMID- 26805919 TI - In vivo degradation of magnesium plate/screw osteosynthesis implant systems: Soft and hard tissue response in a calvarial model in miniature pigs. AB - Biodegradable magnesium plate/screw osteosynthesis systems were implanted on the frontal bone of adult miniature pigs. The chosen implant geometries were based on existing titanium systems used for the treatment of facial fractures. The aim of this study was to evaluate the in vivo degradation and tissue response of the magnesium alloy WE43 with and without a plasma electrolytic surface coating. Of 14 animals, 6 received magnesium implants with surface modification (coated), 6 without surface modification (uncoated), and 2 titanium implants. Radiological examination of the skull was performed at 1, 4, and 8 weeks post-implantation. After euthanasia at 12 and 24 weeks, X-ray, computed tomography, and microfocus computed tomography analyses and histological and histomorphological examinations of the bone/implant blocks were performed. The results showed a good tolerance of the plate/screw system without wound healing disturbance. In the radiological examination, gas pocket formation was found mainly around the uncoated plates 4 weeks after surgery. The micro-CT and histological analyses showed significantly lower corrosion rates and increased bone density and bone implant contact area around the coated screws compared to the uncoated screws at both endpoints. This study shows promising results for the further development of coated magnesium implants for the osteosynthesis of the facial skeleton. PMID- 26805920 TI - Introducing a protocol to create bisphosphonate-related osteonecrosis of the jaw in rat animal model. AB - OBJECTIVE: Previously published animal investigations on bisphosphonate-related osteonecrosis of the jaws (BRONJ) showed a variety of methods for BRONJ induction and inconsistent findings. The aim of present study was to develop a reliable protocol for BRONJ induction in rat animal model. SUBJECTS AND METHODS: In a pilot study, 64 rats were randomly divided into 4 groups and 16 subgroups (each containing 2 experimental and 2 control rats) based on the timing of tooth extraction and euthanasia. The experimental and control rats received intraperitoneal injection of 0.06 mg/kg zoledronate and saline, respectively, once a week until sacrificed, and evaluated for presence of bone exposure clinically, and osteonecrosis and new bone formation histologically. The protocol that successfully produced BRONJ in pilot study was tested in a randomized controlled experimental investigation using 45 rats. RESULTS: In pilot investigation, the highest rate of BRONJ was obtained after four weekly zoledronate injections, at least 4 weeks after tooth extraction. The randomized controlled experimental study verified this finding with a success rate of 83%, and also showed that more prolongation of zoledronate therapy did not increase the BRONJ rate. CONCLUSION: The protocol developed in the present study could be used reliably for future BRONJ investigations on rats. PMID- 26805921 TI - Use of dermis-fat grafts in the prevention of Frey's syndrome after parotidectomy. AB - OBJECTIVE: To examine the role of dermis-fat grafts in preventing gustatory sweating and in the reconstruction of facial contour defects after parotidectomy. PATIENTS: Twenty-three patients with tumours of the parotid gland were enrolled in this prospective clinical study from January 2006 to February 2014. All of them were evaluated for wound complications, Frey's syndrome, satisfaction, and tumour relapse. Follow-up periods ranged from 6 to 72 months. RESULTS: Nineteen patients completed the study. Nine complications observed in six patients were assessed (two haematomas [10%], one seroma [5%], one sialocele [5%], and recurrent pain in five patients [26%]). None revealed Frey's syndrome. Satisfactory results were found in relation to scar, facial contour, and overall outcomes. CONCLUSION: Dermis-fat grafts appear to be an effective method of preventing Frey's syndrome after parotidectomy. The stable long-term results and high patient satisfaction lead to the application of this operation technique in daily routine. PMID- 26805922 TI - Nitrogen transport and transformation in the saturated-unsaturated zone under recharge, runoff, and discharge conditions. AB - Water level (WL) changes are an important factor in the fate and transport of nitrogen in the saturated-unsaturated zone. In this study, the fate of nitrogen was investigated under simulated conditions of replenishment, runoff, and discharge. Three patterns of water level changes of ascent, stability, and descent were simulated under laboratory conditions to study nitrogen transport and transformation. Three columns (I, II, and III) were used to simulate the conditions of replenishment, steady water level, and discharge, respectively. The nitrate-nitrogen (NO3 (-)-N), nitrite-nitrogen (NO2 (-)-N), and ammonia-nitrogen (NH4 (+)-N) concentrations observed at different depths were compared among the three columns at 46.5 and 251.5 h. The results indicated that the NO3 (-)-N concentration decreased with time in both the saturated and unsaturated zones of the three columns (columns I, II, and III). The maximum decreasing concentrations of NO3 (-)-N in the three columns were 14.3, 37.97, and 38.17 mg/L, respectively. However, NH4 (+)-N in the saturated zone increased with time, whereas the NH4 (+) N concentration decreased in both the saturated and unsaturated zones of other columns. No significant change in NO2 (-)-N concentration was observed in the experiment. These results suggest that water level changes must be considered in the remediation of groundwater nitrate pollution in the field. PMID- 26805923 TI - The aquatic fern Azolla as a natural plant-factory for ammonia removal from fish breeding fresh wastewater. AB - This study has investigated the potential of an Azolla-Anabaena symbiosis, a marriage between the cyanobacterium Anabaena azollae and the aquatic fern (Azolla), to remove ammonia from freshwater fish breeding areas. Experiments were carried out under artificial light of 20, 70, and 140 MUmol m(-2) s(-1). We investigated three different water temperatures for the growing Azolla, ranging from sub-optimal to optimal temperatures (15, 22, and 28 degrees C). The capability of Azolla to remove ammonia from wastewater was demonstrated, and the highest ammonia concentration tolerated by the symbiosis between Azolla-anabaena without any toxic effect on the aquatic ferns was ascertained. The shortest time taken to remove ammonia from wastes, 2.5 cm deep and at 28 degrees C, was 40 min. The ammonia removal rate (A RR) was both light and temperature dependent and the highest rate (6.394 h(-1)) was attained at light intensity of 140 MUmol m(-2) s(-1) and at a temperature of 28 degrees C; the lowest (0.947 h(-1)) was achieved at 20 MUmol m(-2) s(-1) and 15 degrees C. The depth of the fish wastewater pool also affected the A RR with the relation between A RR and the depth being a hyperbolic function. PMID- 26805924 TI - Tracking fluorescent dissolved organic matter in multistage rivers using EEM PARAFAC analysis: implications of the secondary tributary remediation for watershed management. AB - Profound understanding of behaviors of organic matter from sources to multistage rivers assists watershed management for improving water quality of river networks in rural areas. Ninety-one water samples were collected from the three orders of receiving rivers in a typical combined polluted subcatchment (diffuse agricultural pollutants and domestic sewage) located in China. Then, the fluorescent dissolved organic matter (FDOM) information for these samples was determined by the excitation-emission matrix coupled with parallel factor analysis (EEM-PARAFAC). Consequently, two typical humic-like (C1 and C2) and other two protein-like (C3 and C4) components were separated. Their fluorescence peaks were located at lambda ex/em = 255(360)/455, <250(320)/395, 275/335, and <250/305 nm, which resembled the traditional peaks of A + C, A + M, T, and B, respectively. In addition, C1 and C2 accounted for the dominant contributions to FDOM (>60 %). Principal component analysis (PCA) further demonstrated that, except for the autochthonous produced C4, the allochthonous components (C1 and C2) had the same terrestrial origins, but C3 might possess the separate anthropogenic and biological sources. Moreover, the spatial heterogeneity of contamination levels was noticeable in multistage rivers, and the allochthonous FDOM was gradually homogenized along the migration directions. Interestingly, the average content of the first three PARAFAC components in secondary tributaries and source pollutants had significantly higher levels than that in subsequent receiving rivers, thus suggesting that the supervision and remediation for secondary tributaries would play a prominent role in watershed management works. PMID- 26805925 TI - Drought prediction and sustainable development of the ecological environment. AB - In the 1990s ecological early warning research began with the aim of elucidating the effect of drought in dry regions of the world. Drought has been a prevalent natural disaster, ravaging the Yun'nan province of China for over 5 years since 2009. Due to the extensive range, depth and devastating losses, the drought has reached a once-in-a-century severity. Yun'nan province suffered particularly badly from the drought, which took its toll on both the ecological environment and the sustainable economic development of the province. We chose to study Pu'er city in Yun'nun province for this research, and analysed the drought traits of Pu'er city utilizing geographic information technology. We applied the Mann Kendall test for trend, linear tendency estimation and percentage of precipitation anomalies, as well as using combinations of monthly data searches of meteorological reports from 1980-2010. The results showed that except for a small rise in spring precipitation, the overall rainfall of Pu'er city showed a decreasing trend. The results of this study can provide an adequate and reliable theoretical basis and technological methods for use in government decision making, and promote research into early warning ecology. PMID- 26805926 TI - Fighting global warming by greenhouse gas removal: destroying atmospheric nitrous oxide thanks to synergies between two breakthrough technologies. AB - Even if humans stop discharging CO2 into the atmosphere, the average global temperature will still increase during this century. A lot of research has been devoted to prevent and reduce the amount of carbon dioxide (CO2) emissions in the atmosphere, in order to mitigate the effects of climate change. Carbon capture and sequestration (CCS) is one of the technologies that might help to limit emissions. In complement, direct CO2 removal from the atmosphere has been proposed after the emissions have occurred. But, the removal of all the excess anthropogenic atmospheric CO2 will not be enough, due to the fact that CO2 outgases from the ocean as its solubility is dependent of its atmospheric partial pressure. Bringing back the Earth average surface temperature to pre-industrial levels would require the removal of all previously emitted CO2. Thus, the atmospheric removal of other greenhouse gases is necessary. This article proposes a combination of disrupting techniques to transform nitrous oxide (N2O), the third most important greenhouse gas (GHG) in terms of current radiative forcing, which is harmful for the ozone layer and possesses quite high global warming potential. Although several scientific publications cite "greenhouse gas removal," to our knowledge, it is the first time innovative solutions are proposed to effectively remove N2O or other GHGs from the atmosphere other than CO2. PMID- 26805928 TI - Photoresponsive Formation of an Intermolecular Minimal G-Quadruplex Motif. AB - The ability of three different bifunctional azobenzene linkers to enable the photoreversible formation of a defined intermolecular two-tetrad G-quadruplex upon UV/Vis irradiation was investigated. Circular dichroism and NMR spectroscopic data showed the formation of G-quadruplexes with K(+) ions at room temperature in all three cases with the corresponding azobenzene linker in an E conformation. However, only the para-para-substituted azobenzene derivative enables photoswitching between a nonpolymorphic, stacked, tetramolecular G quadruplex and an unstructured state after E-Z isomerization. PMID- 26805927 TI - A comprehensive approach to actual polychlorinated biphenyls environmental contamination. AB - Worldwide polychlorinated biphenyls (PCBs) pollution is due to complex mixtures with high number of congeners, making the determination of total PCBs in the environment an open challenge. Because the bulk of PCBs production was made of Aroclor mixtures, this analysis is usually faced by the empirical mixture identification via visual inspection of the chromatogram. However, the identification reliability is questionable, as patterns in real samples are strongly affected by the frequent occurrence of more than one mixture. Our approach is based on the determination of a limited number of congeners chosen to enable objective criteria for Aroclor identification, summing up the advantages of congener-specific analysis with the ones of total PCBs determination. A quantitative relationship is established between congeners and any single mixture, or mixtures combination, leading to the identification of the actual contamination composition. The approach, due to its generality, allows the use of different sets of congeners and any technical mixture, including the non-Aroclor ones. The results confirm that PCB environmental pollution in northern Italy is based on Aroclor. Our methodology represents an important tool to understand the source and fate of the PCBs contamination. PMID- 26805932 TI - Water-mediated influence of a crowded environment on internal vibrations of a protein molecule. AB - The influence of crowding on the protein inner dynamics is examined by putting a single protein molecule close to one or two neighboring protein molecules. The presence of additional molecules influences the amplitudes of protein fluctuations. Also, a weak dynamical coupling of collective velocities of surface atoms of proteins separated by a layer of water is detected. The possible mechanisms of these phenomena are described. The cross-correlation function of the collective velocities of surface atoms of two proteins was decomposed into the Fourier series. The amplitude spectrum displays a peak at low frequencies. Also, the results of principal component analysis suggest that the close presence of an additional protein molecule influences the high-amplitude, low-frequency modes in the most prominent way. This part of the spectrum covers biologically important protein motions. The neighbor-induced changes in the inner dynamics of the protein may be connected with the changes in the velocity power spectrum of interfacial water. The additional protein molecule changes the properties of solvation water and in this way it can influence the dynamics of the second protein. It is suggested that this phenomenon may be described, at first approximation, by a damped oscillator driven by an external random force. This model was successfully applied to conformationally rigid Choristoneura fumiferana antifreeze protein molecules. PMID- 26805930 TI - Risk of prostate cancer-specific death in men with baseline metabolic aberrations treated with androgen deprivation therapy for biochemical recurrence. AB - OBJECTIVES: To investigate the associations of host metabolic factors and metabolic syndrome on prostate cancer-specific death (PCSD) and overall survival (OS) in patients treated with androgen deprivation therapy (ADT) for biochemically recurrent disease. PATIENTS AND METHODS: The analysis included 273 patients with prostate cancer treated with ADT for rising prostate-specific antigen level after surgery or radiotherapy. Patients were assessed for the presence of diabetes, hypertension, dyslipidaemia and obesity before commencing ADT, and Adult Treatment Panel III criteria were used to assess the presence of the composite diagnosis of metabolic syndrome. A competing risks regression model was used to assess associations of time to PCSD with the metabolic conditions, while a multivariable Cox regression model was used to assess associations of OS with metabolic syndrome and metabolic conditions. RESULTS: During a median follow up of 11.6 years, 157 patients (58%) died, of whom 58 (21%) died from prostate cancer. At the start of ADT the median (range) patient age was 74 (46-92) years and the median PSA level was 3.0 ng/mL. Metabolic syndrome was observed in 31% of patients; hypertension (68%) and dyslipidaemia (47%) were the most common metabolic conditions. No association of PCSD and metabolic syndrome status was observed. Patients with hypertension tended to have a higher cumulative incidence of PCSD than those without hypertension (sub-distribution hazard ratio [HR] 1.59, 95% confidence interval [CI] 0.89, 2.84; P = 0.11) although the difference was not statistically significant. Patients with metabolic syndrome had an increased risk of death from all causes (HR 1.56, 95% CI 1.07, 2.29; P = 0.02) when compared with patients without metabolic syndrome, as did patients with hypertension (HR 1.72, 95% CI 1.18, 2.49; P = 0.004). CONCLUSIONS: No association of PCSD and metabolic syndrome was observed in this cohort of men receiving ADT for biochemically recurrent prostate cancer. Metabolic syndrome was associated with an increased risk of death from all causes and a similar effect was also observed for patients with prostate cancer with hypertension alone. PMID- 26805936 TI - Temporal Succession of Ancient Phytoplankton Community in Qinghai Lake and Implication for Paleo-environmental Change. AB - Tibetan lake sediments in NW China are sensitive recorders of climate change. However, many important plankton members do not leave any microscopic features in sedimentary records. Here we used ancient DNA preserved in Qinghai Lake sediments to reconstruct the temporal succession of plankton communities in the past 18,500 years. Our results showed that seven classes and sixteen genera of phytoplankton in the lake underwent major temporal changes, in correlation with known climatic events. Trebouxiophyceae and Eustigmatophyceae were predominant during the cold periods, whereas Chlorophyceae, Phaeophyceae, Xanthophyceae, Bacillariophyceae, and Cyanophyceae were abundant during the warm periods. The inferred changes in temperature, nutrients, precipitation, and salinity, as driven by the Westerlies and summer Monsoon strength, likely contributed to these observed temporal changes. Based on these correlations, we propose the phytoplankton index as a proxy to reconstruct the stadial versus interstadial climate change history in Qinghai Lake. This taxon-specific index is free of terrestrial contamination, sensitive to short-term climatic oscillations, and continuous in recording all climatic events in the lake. The validity of this index and its applicability to other lakes is demonstrated by its good correlations with multiple climate records of Qinghai Lake and another lake on the Tibetan Plateau, Kusai Lake. PMID- 26805933 TI - Common SNP in hsa-miR-196a-2 increases hsa-miR-196a-5p expression and predisposes to idiopathic male infertility in Chinese Han population. AB - MicroRNA plays an important role in spermatogenesis. Whether pre-miRNAs polymorphisms are associated with idiopathic male infertility remains obscure. In this study, 1378 idiopathic infertile males and 486 fertile controls were included between 2006 and 2014. Genotype of three polymorphisms (hsa-mir-146a rs2910164, hsa-mir-196a-2 rs11614913, and hsa-mir-499 rs3746444) and expression of miRNA in seminal plasma were examined by TaqMan method. The role of hsa-miR 196a-5p in cell proliferation, apoptosis and cell cycle were also examined in GC 2 cells. Our results demonstrated that rs11614913 of hsa-miR-196a-2 was significantly associated with idiopathic infertility (TT vs. CT: P = 0.014; TT vs. CC: P = 0.005; TT vs. CT + CC: P = 0.003). In following stratified analysis, we found that rs11614913 exhibited a significantly higher risk of asthenospermia, oligozoospermia and azoospermia. However, no significant association was observed between the other two polymorphisms and idiopathic male infertility risk. In a genotype-expression correlation analysis, rs11614913 CC was significantly associated with elevated expression of hsa-miR-196a-5p (P < 0.05). Additionally, apoptosis levels were significantly increased in hsa-miR-196a-5p mimic treated GC 2 cells, while decreased in hsa-miR-196a-5p inhibitor treated GC-2 cells. Our data revealed a significant relationship between hsa-miR-196a-2 polymorphism and idiopathic male infertility. PMID- 26805937 TI - Tissue-specific expression of ghrelinergic and NUCB2/nesfatin-1 systems in goldfish (Carassius auratus) is modulated by macronutrient composition of diets. AB - The macronutrient composition of diets is a very important factor in the regulation of body weight and metabolism. Several lines of research in mammals have shown that macronutrients differentially regulate metabolic hormones, including ghrelin and nesfatin-1 that have opposing effects on energy balance. This study aimed to determine whether macronutrients modulate the expression of ghrelin and the nucleobindin-2 (NUCB2) encoded nesfatin-1 in goldfish (Carassius auratus). Fish were fed once daily on control, high-carbohydrate, high-protein, high-fat and very high-fat diets for 7 (short-term) or 28 (long-term) days. The expression of preproghrelin, ghrelin O-acyl transferase (goat), growth hormone secretagogue receptor 1 (ghs-r1) and nucb2/nesfatin-1 mRNAs was quantified in the hypothalamus, pituitary, gut and liver. Short-term feeding with fat-enriched diets significantly increased nucb2 mRNA levels in hypothalamus and liver, preproghrelin, goat and ghs-r1 expression in pituitary, and ghs-r1 expression in gut. Fish fed on a high-protein diet exhibited a significant reduction in preproghrelin and ghs-r1 mRNAs in the liver. After long-term feeding, fish fed on high-carbohydrate and very high-fat diets had significantly increased preproghrelin, goat and ghs-r1 expression in pituitary. Feeding on a high carbohydrate diet also upregulated goat and ghs-r1 transcripts in gut, while feeding on a high-fat diet elicited the same effect only for ghs-r1 in liver. Nucb2 expression increased in pituitary, while it decreased in gut after long term feeding of a high-protein diet. Collectively, these results show for the first time in fish that macronutrients differentially regulate the expression of ghrelinergic and NUCB2/nesfatin-1 systems in central and peripheral tissues of goldfish. PMID- 26805938 TI - Understanding the functional impact of copy number alterations in breast cancer using a network modeling approach. AB - Copy number alterations (CNAs) are thought to account for 85% of the variation in gene expression observed among breast tumours. The expression of cis-associated genes is impacted by CNAs occurring at proximal loci of these genes, whereas the expression of trans-associated genes is impacted by CNAs occurring at distal loci. While a majority of these CNA-driven genes responsible for breast tumourigenesis are cis-associated, trans-associated genes are thought to further abet the development of cancer and influence disease outcomes in patients. Here we present a network-based approach that integrates copy-number and expression profiles to identify putative cis- and trans-associated genes in breast cancer pathogenesis. We validate these cis- and trans-associated genes by employing them to subtype a large cohort of breast tumours obtained from the METABRIC consortium, and demonstrate that these genes accurately reconstruct the ten subtypes of breast cancer. We observe that individual breast cancer subtypes are driven by distinct sets of cis- and trans-associated genes. Among the cis associated genes, we recover several known drivers of breast cancer (e.g. CCND1, ERRB2, MDM2 and ZNF703) and some novel putative drivers (e.g. BRF2 and SF3B3). siRNA-mediated knockdown of BRF2 across a panel of breast cancer cell lines showed significant reduction in cell viability for ER-/HER2+ (MDA-MB-453) cells, but not in normal (MCF10A) cells thereby indicating that BRF2 could be a viable therapeutic target for estrogen receptor-negative/HER2-enriched (ER-/HER2+) cancers. Among the trans-associated genes, we identify modules of immune response (CD2, CD19, CD38 and CD79B), mitotic/cell-cycle kinases (e.g. AURKB, MELK, PLK1 and TTK), and DNA-damage response genes (e.g. RFC4 and FEN1). siRNA-mediated knockdown of RFC4 significantly reduced cell proliferation in ER-negative normal breast and cancer lines, thereby indicating that RFC4 is essential for both normal and cancer cell survival but could be a useful biomarker for aggressive (ER-negative) breast tumours. AVAILABILITY: under NetStrat. PMID- 26805939 TI - Sub-Coronal Inflatable Penile Prosthesis Placement With Modified No-Touch Technique: A Step-by-Step Approach With Outcomes. AB - INTRODUCTION: The surgical treatment of disorders of male sexual function requires specific exposure to correct the underlying problem safely and efficiently. Currently, sub-coronal exposure is used for treatment of phimosis, Peyronie's disease plaque (PDP), and semirigid penile prosthesis insertion. Infra pubic and scrotal incisions are used for inflatable penile prosthesis (IPP) placement. However, men who present with several disorders might require multiple procedures and surgical incisions. AIM: To report a prospective review of our surgical experience and outcomes with a single sub-coronal incision for IPP placement with a modified no-touch technique. This approach allows for access to the entire corporal body for multiple reconstructive procedures. METHODS: Two hundred men had IPPs placed through a sub-coronal incision using our modified no touch technique. The penis was degloved to the level of the penoscrotal junction and the dartos muscle was everted and secured to the drapes. This allowed exclusion of the scrotal and penile skin from the operative field. After artificial erection, the patient's corpora were inspected for PDP and other abnormalities. Penoscrotal IPP models were placed in all cases with insertion proximal to the penoscrotal junction. After placement of the IPP, the abnormalities were repaired. MAIN OUTCOME MEASURES: Feasibility of the procedure, operative times, complication rate, utilization of accessory, reconstructive procedures, and post-operative penile length. RESULTS: Of the 200 men who had IPP placement, 92 had PDP that was treated, 106 (53%) consented to circumcision, 24 (12%) had their reservoir placed ectopically, and 31 (16%) had a prosthesis exchanged through the sub-coronal technique. Mean operative time was 73 minutes (39-161 minutes). CONCLUSION: Specialists in the surgical treatment of disorders of male sexual function can perform multiple procedures safely and easily through a modified no-touch single sub-coronal incision. This approach allows access to the entire corporal body, providing excellent visibility and allowing the surgeon to perform multiple penile reconstructive surgeries through a single incision. PMID- 26805940 TI - The Impact of Sacrospinous Hysteropexy and Vaginal Hysterectomy With Suspension of the Uterosacral Ligaments on Sexual Function in Women With Uterine Prolapse: A Secondary Analysis of a Randomized Comparative Study. AB - INTRODUCTION: Studies on pelvic organ prolapse (POP) surgery show conflicting evidence regarding the impact of uterus preservation and hysterectomy on sexual function and no large randomized trials with long-term follow-up have been published on this topic. AIMS: The aim of this secondary analysis was to evaluate and compare sexual function after sacrospinous hysteropexy and vaginal hysterectomy with suspension of the uterosacral ligaments in women with uterine prolapse. METHODS: This is a secondary analysis of the SAVE U trial data, a multicenter trial in 4 nonuniversity hospitals in the Netherlands comparing sacrospinous hysteropexy and vaginal hysterectomy with suspension of the uterosacral ligaments in primary surgery of uterine prolapse stage II or higher. Primary outcome of the original study was recurrent prolapse stage II or higher of the uterus or vaginal vault (apical compartment) evaluated by POP-Q examination in combination with bothersome bulge symptoms or repeat surgery for recurrent apical prolapse at 12 months follow-up. Secondary outcomes were overall anatomical recurrences, functional outcome, complications, hospital stay, postoperative recovery, and sexual functioning. Data from patients who had completed the POP/urinary incontinence sexual questionnaire (PISQ-12) at baseline and 24 months after surgery were used in the present trial. Total, subscale, and individual question analyses were performed. The SAVE U trial is registered in the Dutch trial registry, number NTR1866. MAIN OUTCOME MEASURES: Differences and changes in sexual function 24 months after surgery, measured by the PISQ-12 questionnaire. RESULTS: Between November 2009 and March 2012, 208 women were randomized between sacrospinous hysteropexy (n = 103) and vaginal hysterectomy with suspension of the uterosacral ligaments (n = 105). Of these, 99 women completed questionnaires at baseline and after 24 months follow-up and were included in the present study. During a follow-up period of 24 months, no significant differences in total PISQ-12 scores were observed between the groups. After both interventions the item "avoidance of intercourse due to prolapse" significantly improved, as did the physical subscale of the PISQ-12 questionnaire. CONCLUSION: There was no statistically significant difference in overall sexual functioning (total PISQ-12 scores) between uterus-preserving sacrospinous hysteropexy and vaginal hysterectomy with suspension of the uterosacral ligaments after a follow-up period of 24 months. PMID- 26805941 TI - Comparison of Treatment Emergent Adverse Events in Men With Premature Ejaculation Treated With Dapoxetine and Alternate Oral Treatments: Results From a Large Multinational Observational Trial. AB - INTRODUCTION: Dapoxetine (DPX) has a pharmacokinetic profile suggesting a low rate of class-related adverse events (AEs). AIM: To assess the incidence of treatment emergent AEs (TEAEs) of special interest (known associations with selective serotonin reuptake inhibitors and/or potential clinically relevant AEs), and the related discontinuation rate in patients with premature ejaculation (PE) treated with DPX or alternate oral treatment (AOT), in routine clinical practice. METHODS: In a prospective, 12-week, open-label, postmarketing observational, multinational study (PAUSE), 7545 patients were enrolled and divided into 2 groups: DPX 30-60 mg and AOT. MAIN OUTCOME MEASURES: The incidence rate of predefined TEAEs of special interest (mood and related, neurocognitive related, cardiovascular, urogenital and sexual function, accidental injury, and abnormal bleeding) in the DPX and the AOT groups, and the rate of AEs leading to study discontinuation. RESULTS: The safety analysis was performed on 6128 patients treated with DPX and 1417 with AOT. The incidence of TEAEs of special interest in each AE category was greater for patients treated with AOT than with DPX. The higher differences were observed in the neurocognitive-related category (DPX 1.9% vs. AOT 4.7%; P < .001), in the mood and related category (DPX 0.4% vs. AOT 1.1%; P < .001), and in the urogenital system/sexual function (DPX 0.4% vs. AOT 0.8%; P = .04). Cardiovascular TEAEs were the only AEs numerically greater in the DPX group (1.3 vs. 1.6%, P = .34). The overall discontinuation rate was 10.9% in the DPX group and 6.9% in the AOT group). CONCLUSION: DPX has a favorable safety profile in terms of class-related TEAEs and clinically relevant AEs of special interest. In particular, it shows a significantly better safety profile in mood and related AEs, neurocognitive-related AEs, urogenital system, and sexual function, compared to the AOT group in the study population. PMID- 26805942 TI - Differences in the Biometry of the Levator Hiatus at Rest, During Contraction, and During Valsalva Maneuver Between Women With and Without Provoked Vestibulodynia Assessed by Transperineal Ultrasound Imaging. AB - INTRODUCTION: Pelvic floor muscle (PFM) involvement is suspected in the pathophysiology of provoked vestibulodynia (PVD); however, the underlying mechanisms are unclear. PFM morphology can be inferred from the biometry of the levator hiatus determined through dynamic ultrasound imaging. AIMS: The aim of this study was to determine the nature of PFM involvement in women with PVD via an evaluation of the biometry of the levator hiatus at rest, upon maximal voluntary contraction (MVC) of the PFMs, and upon maximal Valsalva maneuver (MVM). METHODS: Thirty-eight women with PVD and 39 asymptomatic controls were imaged using 3D transperineal ultrasound. Levator hiatal dimensions (area; left right [LR] and anteroposterior [AP] diameters) were measured at rest, on MVC, and on MVM. Differences in hiatal dimensions and in relative changes in dimensions from rest to MVC and from rest to MVM were compared between groups using separate 1-way analyses of variance for each measure and task. Analysis of covariance models were used to investigate the impact of levator hiatal dimensions at rest on the relative changes in the levator hiatal dimensions during MVC and MVM. MAIN OUTCOME MEASURES: Levator hiatal area, LR, and AP diameters, at rest, on MVC, and on MVM were the main outcome measures. Relative changes in hiatal dimensions were assessed as the percent change in hiatal area, LR diameter, and AP diameter. RESULTS: In comparison with controls, women with PVD had smaller hiatal areas at rest, on MVC, and on MVM, concurrent with smaller LR diameters on MVM. Women with PVD had a significantly smaller change in hiatal area on MVM than controls, but no differences were evident on MVC. In both groups, smaller levator hiatal dimensions at rest were associated with smaller relative decreases in dimensions on MVC and larger relative increases in dimensions on MVM. CONCLUSION: In comparison to controls, women with PVD appear to have narrower levator hiatus' and less capacity to distend their hiatus on Valsalva. The state of the PFMs at rest appears to significantly influence biometric changes in the PFMs during contraction and Valsalva. PMID- 26805944 TI - Colorectal adenomatous polyposis syndromes: Genetic determinism, clinical presentation and recommendations for care. AB - Colorectal adenomatous polyposis constitutes a diverse group of disorders with different modes of inheritance. Molecular diagnosis of this condition has become more complex. In fact, somatic mosaicism for APC mutations now appears to be more frequent than previously thought and rare germline alterations of this gene may be implicated in patients tested negative for "classical" APC mutations (point mutations and large genomic rearrangements). Moreover, the knowledge concerning several aspects of the MUTYH-associated polyposis has improved since its first description in 2002 and germline mutations in new genes have recently been implicated in some cases of unexplained adenomatous polyposis. Genetic testing in probands and their relatives should be conducted in the context of pre- and post test genetic counseling. The recent advent of New Generation Sequencing (NGS) techniques affords the opportunity to rapidly screen patients for a comprehensive panel of colorectal cancer susceptibility genes in a cost-effective fashion. This type of approach will probably replace the classical sequential approach based on clinical presumptive diagnoses in the near future. The risk of colorectal cancer is very high in affected patients in the absence of appropriate care. Clinical management is complex and should be provided in centers with special expertise in these diseases. This review focuses on the various colorectal adenomatous polyposis syndromes with special attention to more innovative and important aspects. PMID- 26805947 TI - Abstracts of the 4th European Confederation of Medical Mycology Educational Symposium, 14-16 February 2016, Tel Aviv, Israel. PMID- 26805945 TI - Massive sigmoid volvulus. PMID- 26805948 TI - Performance of the revised Atlanta and determinant-based classifications for severity in acute pancreatitis. AB - BACKGROUND: Severity classification systems aim to stratify patients with acute pancreatitis reliably into coherent risk groups. Recently, the Atlanta 1992 classification has been revised (Atlanta 2012) and a novel determinant-based classification (DBC) system developed. This study assessed the ability of the three systems to stratify disease severity among patients with acute pancreatitis. METHODS: This was an observational cohort study of patients with acute pancreatitis identified from an institutional database. Cohort characteristics, investigations, interventions and outcomes were identified. Systems were compared using receiver operating characteristic (ROC) analysis and Spearman's correlation coefficients. RESULTS: The in-hospital mortality rate was 6.6 per cent (15 of 228 patients). All of the outcomes considered correlated significantly with the three systems, with the exception of the need for surgery in Atlanta 1992. Atlanta 2012 and the DBC had higher area under the curve (AUC) values than Atlanta 1992 for all outcomes. The revised Atlanta and DBC systems both performed similarly with regard to ICU admission (AUC 0.927 and 0.917 respectively; both P < 0.001), need for percutaneous drainage (AUC 0.879 and 0.891; both P < 0.001), need for surgery (AUC 0.827 and 0.845; P = 0.006 and P = 0.004 respectively) and in-hospital mortality (0.955 and 0.931; both P < 0.001). However, the critical category in the DBC system identified patients with the most severe disease; seven of eight patients in this group died in hospital, compared with 15 of 34 with severe pancreatitis according to Atlanta 2012. CONCLUSION: The Atlanta 2012 and DBC perform equally well for classification of disease severity in acute pancreatitis. The addition of a critical category in the DBC identifies patients with the most severe disease. PMID- 26805949 TI - Accelerated soil carbon turnover under tree plantations limits soil carbon storage. AB - The replacement of native forests by tree plantations is increasingly common globally, especially in tropical and subtropical areas. Improving our understanding of the long-term effects of this replacement on soil organic carbon (SOC) remains paramount for effectively managing ecosystems to mitigate anthropogenic carbon emissions. Meta-analyses imply that native forest replacement usually reduces SOC stocks and may switch the forest from a net sink to a net source of atmospheric carbon. Using a long-term chronosequence during which areas of subtropical native forest were replaced by Chinese fir, we show by direct measurement that plantations have significantly accelerated SOC turnover compared with native forest, an effect that has persisted for almost a century. The immediate stimulation of SOC decomposition was caused by warmer soil before the closure of the plantation's canopy. Long-term reductions in SOC mean residence times were coupled to litter inputs. Faster SOC decomposition was associated with lower soil microbial carbon use efficiency, which was due to smaller litter inputs and reduced nutrient availabilities. Our results indicate a previously unelucidated control on long-term SOC dynamics in native forests and demonstrate a potential constraint on climate mitigation when such forests are replaced by plantations. PMID- 26805950 TI - Localization and role of MYO-1, an endocytic protein in hyphae of Neurospora crassa. AB - The subapical endocytic collar is a prominent feature of hyphae of Neurospora crassa. It comprises a dynamic collection of actin patches associated with a number of proteins required for endocytosis, namely, ARP-2/3 complex, fimbrin, coronin, etc. We presently show that MYO-1 is another key component of this endocytic collar. A myo-1 sequence was identified in the genome of N. crassa and used it to generate a strain with a myo-1-sgfp allele under the ccg1 promoter. Examination of living hyphae by confocal microscopy, revealed MYO-1-GFP located mainly as a dynamic collection of small patches arranged in collar-like fashion in the hyphal subapex. Dual tagging showed MYO-1-GFP partially colocalized with two other endocytic proteins, fimbrin and coronin. MYO-1 was also present during septum formation. By recovering a viable strain, albeit severely inhibited, after deletion of myo-1, it was possible to investigate the phenotypic consequences of the elimination of MYO-1. Deletion of myo-1 caused a severe reduction in growth rate (95%), near absence of aerial mycelium and no conidiation. A reduced uptake of the lipophilic dye FM4-64 indicated a deficiency in endocytosis in the Deltamyo-1 mutant. Hyphae were produced by the Deltamyo-1 mutant but their morphogenesis was severely affected; hyphal morphology was distorted displaying irregular periods of isotropic and polarized growth. The morphological alterations were accompanied, and presumably caused, by a disruption in the organization and dynamics of a myosin-deprived actin cytoskeleton that, ultimately, compromised the stability and function of the Spitzenkorper as a vesicle supply center. PMID- 26805951 TI - Noble Metal-Iron Oxide Hybrid Nanomaterials: Emerging Applications. AB - This account provides an overview of current research activities that focus on the synthesis and applications of nanomaterials from noble metal (e.g., Au, Ag, Pd) and iron oxide (Fe3O4) hybrids. An introduction to the synthetic strategies that have been developed for generating M-Fe3O4 nanomaterials with different novel structures is presented. Surface functionalization and bioconjugation of these hybrid nanoparticles and nanocomposites are also reviewed. The utilization of the advantageous properties of both noble metals and iron oxide for a variety of applications, such as theranostics, gene delivery, biosensing, cell sorting, bioseparation, and catalysis, is discussed and highlighted. Finally, future trends and perspectives of these sophisticated nanocomposites are outlined. The fundamental requirements underpinning the effective preparation of M-Fex Oy hybrid nanomaterials shed light on the future development of heterogeneous catalysts, nanotheranostics, nanomedicines, and other chemical technologies. PMID- 26805952 TI - Rapid responses to steroid hormones light up daily life. PMID- 26805953 TI - Does the primate pattern hold up? Testing the functional significance of infraorbital foramen size variation among marsupials. AB - OBJECTIVES: The relative size of the infraorbital foramen (IOF) has been used to infer the ecology of extinct primates for several decades. Primates have relatively smaller IOFs than most other mammals, which may result from the fact that they pre-process and manipulate food with their hands rather than their muzzles. In primates, relative IOF area co-varies with diet, where insectivores and folivores have relatively smaller IOFs than frugivores. We wanted to determine whether the observed patterns associated with IOF variation hold across other orders. MATERIALS AND METHODS: We examined how relative IOF area differs among marsupials occupying different ecological niches. Marsupials were chosen because they converge with primates in both ecology and morphology, but unlike primates, some marsupials approach and pre-process foods only with their muzzles. We measured IOF area and cranial lengths from 72 marsupial species, and behavioral feeding data were obtained from a subset of this sample (N = 20). RESULTS: Relative IOF area did not vary significantly between substrate preferences. However, relative IOF area differed significantly by diet category (P < 0.001). Species that specialize in feeding on non-grassy leaves have significantly smaller relative IOF areas than species which primarily feed on grasses, insects, vertebrates, or some combination thereof. Behavioral analyses support that folivorous marsupials approach and remove food with the hands more often than marsupials from other dietary groups. DISCUSSION: Results suggest that relatively small IOF area may reflect increased reliance on the hands while feeding, and that relative IOF size can be used as an indicator of feeding behavior. PMID- 26805955 TI - Separation Science in Latin America. PMID- 26805954 TI - Population Connectivity Measures of Fishery-Targeted Coral Reef Species to Inform Marine Reserve Network Design in Fiji. AB - Coral reef fish serve as food sources to coastal communities worldwide, yet are vulnerable to mounting anthropogenic pressures like overfishing and climate change. Marine reserve networks have become important tools for mitigating these pressures, and one of the most critical factors in determining their spatial design is the degree of connectivity among different populations of species prioritized for protection. To help inform the spatial design of an expanded reserve network in Fiji, we used rapidly evolving mitochondrial genes to investigate connectivity patterns of three coral reef species targeted by fisheries in Fiji: Epinephelus merra (Serranidae), Halichoeres trimaculatus (Labridae), and Holothuria atra (Holothuriidae). The two fish species, E. merra and Ha. trimaculatus, exhibited low genetic structuring and high amounts of gene flow, whereas the sea cucumber Ho. atra displayed high genetic partitioning and predominantly westward gene flow. The idiosyncratic patterns observed among these species indicate that patterns of connectivity in Fiji are likely determined by a combination of oceanographic and ecological characteristics. Our data indicate that in the cases of species with high connectivity, other factors such as representation or political availability may dictate where reserves are placed. In low connectivity species, ensuring upstream and downstream connections is critical. PMID- 26805956 TI - Simultaneous determination and pharmacokinetics of five alkaloids in rat plasma by ultra high performance liquid chromatography with tandem mass spectrometry after the oral administration of Corydalis bungeana Turcz extract. AB - Pharmacokinetic studies were conducted on rats for protopine, corynoline, 7' (3',4'-dihydroxyphenyl)-N-[(4-methoxyphenyl)-ethyl]propenamide, acetylcorynoline, and 8-oxocorynoline, five main active components from Corydalis bungeana Turcz (C. bungeana Turcz). An ultra high performance liquid chromatography with tandem mass spectrometry method has been developed and validated for the simultaneous determination of the pharmacokinetic characteristics of these components in rat plasma. Chromatographic separation was achieved on an Agilent SB-C18 column (1.8 MUm, 150 * 2.1 mm) using a gradient elution program with a mobile phase consisting of acetonitrile and water containing 0.1% acetic acid at a flow rate of 0.3 mL/min. The analytes were detected in the multiple reaction monitoring mode with positive electrospray ionization. Lower limits of quantification were >0.680 ng/mL and matrix effects ranged from 91.26 to 100.38%. The mean extraction recoveries of quality control samples were less than 79.32%, and the precision and accuracy were within the acceptable limits. All analytes were proven to be stable during sample storage and analysis procedures. The validated method was successfully applied to the pharmacokinetic study of five alkaloid components after oral administration of C. bungeana Turcz extract to rats. The obtained results may be helpful to reveal the mechanism of action and to guide the clinical application of C. bungeana Turcz. PMID- 26805957 TI - Determination of volatile chlorinated hydrocarbons in water samples by static headspace gas chromatography with electron capture detection. AB - A simple, efficient, solvent-free, and commercial readily available approach for determination of five volatile chlorinated hydrocarbons in water samples using the static headspace sampling and gas chromatography with electron capture detection has been described. The proposed static headspace sampling method was initially optimized and the optimum experimental conditions found were 10 mL water sample containing 20% w/v sodium chloride placed in a 20 mL vial and stirred at 50oC for 20 min. The linearity of the method was in the range of 1.2 240 MUg/L for dichloromethane, 0.2-40 MUg/L for trichloromethane, 0.005-1 MUg/L for perchloromethane, 0.025-5 MUg/L for trichloroethylene, and 0.01-2 MUg/L for perchloroethylene, with coefficients of determination ranging between 0.9979 and 0.9990. The limits of detection were in the low MUg/L level, ranging between 0.001 and 0.3 MUg/L. The relative recoveries of spiked five volatile chlorinated hydrocarbons with external calibration method at different concentration levels in pure, tap, sea water of Jiaojiang Estuary, and sea water of waters of Xiaomendao were in the range of 91-116, 96-105, 86-112, and 80-111%, respectively, and with relative standard deviations of 1.9-3.6, 2.3-3.5, 1.5-2.7, and 2.3-3.7% (n = 5), respectively. The performance of the proposed method was compared with traditional liquid-liquid extraction on the real water samples (i.e., pure, tap, and sea water, etc.) and comparable efficiencies were obtained. It is concluded that this method can be successfully applied for the determination of volatile chlorinated hydrocarbons in different water samples. PMID- 26805958 TI - Recovery and separation of erythromycin from industrial wastewater by imprinted magnetic nanoparticles that exploit beta-cyclodextrin as the functional monomer. AB - A type of surface imprinting over magnetic Fe3 O4 nanoparticles utilizing erythromycin-A as a template for use in the separation and recovery of erythromycin was developed and investigated. As the intermolecular forces play a key role in the performance of imprinted materials, differential scanning calorimetry, and (1) H NMR spectroscopy was employed to evaluate the interactions between erythromycin and the functional monomer beta-cyclodextrin. To synthesize the surface imprinted polymers, magnetic Fe3 O4 nanoparticles, the core materials, were modified with a free radical initiator to initialize polymerization in a "grafting from" manner. Then using acryloyl-modified beta cyclodextrin as the functional monomer and ethyleneglycol dimethacrylate as the cross-linker, thin erythromycin-imprinted films were fabricated by the radical induced graft copolymerization of monomers on the surface of the Fe3 O4 nanoparticles. Selectivity experiments showed that the erythromycin-A-imprinted materials had recognition ability toward erythromycin derivatives. Finally, these magnetic molecularly imprinted particles were successfully used for the separation and enrichment of erythromycin from the mother liquor. The recovery, detected by high-performance liquid chromatography and differential pulse voltammetry, approached 97%. The combination of the specific selectivity of the imprinted material and the magnetic separation provided a powerful tool that is simple, flexible, and selective for the separation and recovery of erythromycin. PMID- 26805961 TI - A current perspective of supercharging reagents and peptide bioanalysis. PMID- 26805963 TI - Induction of protumoral CD11c(high) macrophages by glioma cancer stem cells through GM-CSF. AB - Cancer stem cells (CSCs) are maintained under special microenvironment called niche, and elucidation and targeting of the CSC niche will be a feasible strategy for cancer eradication. Tumor-associated macrophages (TAMs) are known to be involved in cancer progression and thus can be a component of CSC niche. Although TAMs are known to play multiple roles in tumor progression, involvement of CSCs in TAM development fully remains to be elucidated. Using rat C6 glioma side population (SP) cells as a model of glioma CSCs, we here show that CSCs induce the TAM development by promoting survival and differentiation of bone marrow derived monocytes. CSC-induced macrophages can be separated into two distinct subsets of cells, CD11c(low) and CD11c(high) cells. Interestingly, only the CD11c(high) subset of cells have protumoral activity, as shown by intracranial transplantation into immune-deficient mice together with CSCs. These CD11c(high) macrophages were observed in the tumor formed by co-transplantation with CSCs. Furthermore, CSCs produced GM-CSF and anti-GM-CSF antibody inhibited CSC-induced TAM development. In conclusion, CSCs have the ability to self-create their own niche involving TAMs through CSC-derived GM-CSF, which can thus be a therapeutic target in view of CSC niche disruption. PMID- 26805964 TI - Effects of rutin and buckwheat seeds on energy metabolism and methane production in dairy cows. AB - Flavonoids are secondary plant metabolites with several health promoting effects. As dairy cows often suffer from metabolic imbalance and health problems, interest is growing in health improvements by plant substances such as flavonoids. Our group has recently shown that the flavonoids quercetin and rutin (a glucorhamnoside of quercetin) are bioavailable in cows when given via a duodenal fistula or orally, respectively, affect glucose metabolism, and have beneficial effects on liver health. Furthermore, flavonoids may reduce rumen methane production in vitro through their antibacterial properties. To test the hypothesis that rutin has effects on energy metabolism, methane production, and production performance in dairy cows, we fed rutin trihydrate at a dose of 100mg/kg of body weight to a group of 7 lactating dairy cows for 2 wk in a crossover design. In a second experiment, 2 cows were fed the same ration but were supplemented with buckwheat seeds (Fagopyrum tartaricum), providing rutin at a dose comparable to the first experiment. Two other cows receiving barley supplements were used as controls in a change-over mode. Blood samples were taken weekly and respiration measurements were performed at the end of each treatment. Supplementation of pure rutin, but not of rutin contained in buckwheat seeds, increased the plasma quercetin content. Methane production and milk yield and composition were not affected by rutin treatment in either form. Plasma glucose, beta-hydroxybutyrate, and albumin were increased by pure rutin treatment, indicating a possible metabolic effect of rutin on energy metabolism of dairy cows. In addition, we did not show that in vivo ruminal methane production was reduced by rutin. In conclusion, we could not confirm earlier reports on in vitro methane reduction by rutin supplementation in dairy cows in established lactation. PMID- 26805965 TI - Comparative activities of milk components in reversing chronic colitis. AB - Inflammatory bowel disease (IBD) is a poorly understood chronic immune disorder for which there is no medical cure. Milk and colostrum are rich sources of bioactives with immunomodulatory properties. Here we compared the therapeutic effects of oral delivery of bovine milk-derived iron-saturated lactoferrin (Fe bLF), angiogenin, osteopontin (OPN), colostrum whey protein, Modulen IBD (Nestle Healthsciences, Rhodes, Australia), and cis-9,trans-11 conjugated linoleic acid (CLA)-enriched milk fat in a mouse model of dextran sulfate-induced colitis. The CLA-enriched milk fat significantly increased mouse body weights after 24d of treatment, reduced epithelium damage, and downregulated the expression of proinflammatory cytokines and nitrous oxide. Modulen IBD most effectively decreased the clinical score at d 12, and Modulen IBD and OPN most effectively lowered the inflammatory score. Myeloperoxidase activity that denotes neutrophil infiltration was significantly lower in mice fed Modulen IBD, OPN, angiogenin, and Fe-bLF. A significant decrease in the numbers of T cells, natural killer cells, dendritic cells, and a significant decrease in cytokine expression were observed in mice fed the treatment diets compared with dextran sulfate administered mice. The Fe-bLF, CLA-enriched milk fat, and Modulen IBD inhibited intestinal angiogenesis. In summary, each of the milk components attenuated IBD in mice, but with differing effectiveness against specific disease parameters. PMID- 26805967 TI - Efficiency and rumen responses in younger and older Holstein heifers limit-fed diets of differing energy density. AB - The objective of this study was to evaluate the effects of limit feeding diets of different predicted energy density on the efficiency of utilization of feed and nitrogen and rumen responses in younger and older Holstein heifers. Eight rumen cannulated Holstein heifers (4 heifers beginning at 257 +/- 7 d, hereafter "young," and 4 heifers beginning at 610 +/- 16 d, hereafter "old") were limit-fed high [HED; 2.64 Mcal/kg of dry matter (DM), 15.31% crude protein (CP)] or low (LED; 2.42 Mcal/kg of DM, 14.15% CP) energy density diets according to a 4 period, split-plot Latin square design with 28-d periods. Diets were limit-fed to provide isonitrogenous and isoenergetic intake on a rumen empty body weight (BW) basis at a level predicted to support approximately 800 g/d of average daily gain. During the last 7d of each period, rumen contents were subsampled over a 24 h period, rumen contents were completely evacuated, and total collection of feces and urine was made over 4d. Intakes of DM and water were greater for heifers fed LED, although, by design, calculated intake of metabolizable energy did not differ between age groups or diets when expressed relative to rumen empty BW. Rumen pH was lower, ammonia (NH3-N) concentration tended to be higher, and volatile fatty acids (VFA) concentration was not different for HED compared with LED and was unaffected by age group. Rumen content mass was greater for heifers fed LED and for old heifers, so when expressing rumen fermentation responses corrected for this difference in pool size, NH3-N pool size was not different between diets and total moles of VFA in the rumen were greater for heifers fed LED, whereas these pool sizes were greater for old heifers. Total-tract digestibility of potentially digestible neutral detergent fiber (NDF) was greater in heifers fed LED and for young heifers, whereas the fractional rate of ruminal passage and digestion of NDF were both greater in heifers fed LED. Digestibility of N was greater for heifers fed HED, but was unaffected by age group, whereas the efficiency of N retention was greater for heifers fed HED and for young heifers. Manure output was reduced in heifers fed HED, but the effect was largest in old heifers. Results confirm previous studies in which young heifers utilize N more efficiently than old heifers, primarily through greater efficiency of postabsorptive metabolism. Results also support the concept of limit feeding HED diets as a potential means to reduce manure excretion and increase nitrogen efficiency. PMID- 26805966 TI - Economic and environmental effects of providing increased amounts of solid feed to veal calves. AB - Traditionally, veal calves receive most of their nutrients from milk replacer (MR). Nowadays, however, solid feed (SF; i.e., concentrates and roughages) increasingly substitutes for MR. Studies have shown that providing SF reduces different types of nonnutritive oral behaviors. The objective of this study was to assess the economic and environmental effects of substituting SF for MR in veal calf diets. With respect to environmental effects, we considered the emission of greenhouse gases and land occupation. Substitution rates were based on an experiment in which 160 calves were provided 2 mixtures of SF at 4 levels of dry matter (DM) intake. Mixtures of SF contained either 80% concentrates, 10% corn silage, and 10% straw on DM basis (C80) or 50% concentrates, 25% corn silage, and 25% straw (C50). The 4 levels of SF during the last 17 wk of the fattening period were 20, 100, 180, and 260 kg of DM SF. Additionally, provision of MR was adjusted to achieve equal rates of carcass gain. Substitution rates, representing the SF equivalent needed to substitute for 1 kg of DM MR, were 1.43 kg of DM for C80 and 1.61 kg of DM for C50. Economic effects were assessed based on prices and substitution rates of SF for MR and the possible penalty for carcass color. Environmental effects were assessed based on effects related to the production of feed ingredients, substitution rates, and changes in enteric methane emission and energy use for feed preparation. Costs of feeding SF needed to substitute for 1 kg of DM MR were ?0.68 lower for C80 and ?0.71 lower for C50, compared with the costs of feeding 1 kg of DM MR. When carcass color scores became too high, however, lower feeding costs were offset by lower revenues from meat. Emissions of greenhouse gases were hardly affected when SF intake was increased. In general, increased enteric methane emission were offset by lower emissions from feed production and energy use. Land occupation increased when intake of SF was increased, mostly because of the high land occupation associated with some concentrate ingredients. In conclusion, this study only showed a negative effect on land occupation when substituting SF for part of the MR in diets of veal calves. Effects on costs and greenhouse gas emissions were neutral or positive. PMID- 26805968 TI - Short communication: Lactational responses to palmitic acid supplementation when replacing soyhulls or dry ground corn. AB - The objective of this study was to evaluate the response of mid-lactation dairy cows to a palmitic acid (C16:0)-enriched fatty acid supplement when replacing soyhulls or dry ground corn in the diet. Twenty-four multiparous Holstein cows (182 +/- 60 d in milk; mean +/- SD) were blocked by preliminary 3.5% fat corrected milk and randomly assigned to treatment sequence in a replicated 3 * 3 Latin square design with 21-d periods. Treatments consisted of a control diet containing no supplemental fat (CON), and 2 C16:0-enriched fatty acid supplemented treatments (PA; BergaFat F100, Berg & Schmidt, Hanover, Germany) as a replacement for either soyhulls (PA-SH) or dry ground corn (PA-CG). The C16:0 enriched supplement was fed at 1.5% of diet dry matter. The PA treatments did not affect dry matter intake, but PA-SH increased dry matter intake by 1.4 kg/d compared with PA-CG. The PA treatments did not affect milk yield; however, PA-SH increased milk yield by 2.4 kg/d compared with PA-CG. The PA treatments tended to decrease milk protein content (3.12 vs. 3.15%). In contrast, PA-SH increased milk protein content (3.14 vs. 3.10%) and milk protein yield (1.27 vs. 1.19 kg/d) compared with PA-CG. The PA treatments increased milk fat concentration (3.68 vs. 3.55%) and milk fat yield (1.46 vs. 1.38 kg/d). The increase in milk fat yield with PA treatments was due to the increase in the yield of 16-carbon fatty acid in milk fat. Furthermore, PA-SH tended to increase yield of de novo fatty acids and yield of 16-carbon fatty acids compared with PA-CG. The PA treatments tended to increase feed efficiency (3.5% fat-corrected milk/dry matter intake) compared with CON (1.51 vs. 1.46). The PA-SH treatment tended to increase insulin concentration compared with PA-CG (1.58 vs. 1.49 MUg/L) and PA treatments increased nonesterified fatty acids compared with CON (110 vs. 99 MUEq/L). Overall, PA treatments improved feed efficiency and increased milk fat yield and the response to the C16:0-enriched fatty acid supplement was greater when it replaced soyhulls compared with when it replaced dry ground corn in the diet. PMID- 26805969 TI - Short communication: Role of Streptococcus pluranimalium in Mediterranean buffaloes (Bubalus bubalis) with different udder health statuses. AB - The aims of the current study were to describe presence and clinical role over time of Streptococcus pluranimalium isolated in milk samples of Mediterranean buffalo (MB). Two hundred composite milk samples originating from 40 primiparous MB were collected at 10, 30, 60, 90, and 150d in milk (DIM) and from 20 pluriparous MB at 77 to 120 DIM. Milk samples were used for analysis of somatic cell counts, bacteriological cultures, and identification (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry). Nine of 200 (4.5%) samples of primiparous MB and 3 of 20 (15%) samples of pluriparous MB were positive for Strep. pluranimalium. The prevalence of the bacterium in primipari was 0% (0/40) at 10, 30, and 150 DIM, whereas it was 5 (2/40) and 17.5% (7/40) at 60 and 90 DIM, respectively. Eight primipari were positive only once, whereas 1 was positive at 2 different samplings. Mono-infection was not detected in any of the age categories or udder health status. Infections were transient in primipari. Clinical mastitis was observed in primipari once at 90 DIM, subclinical mastitis detected twice in the same animals at 60 and 90 DIM, and intramammary infections were diagnosed 1 and 5 times at 60 and 90 DIM in primipari, respectively, whereas 3 infections were diagnosed in pluripari. The clinical reflections demonstrate for the first time the presence of Strep. pluranimalium in MB and its association with different udder health status. Nevertheless, it cannot be excluded that the bacterium may simply follow a pattern of commensal or opportunistic behavior, taking advantage of a preexisting bacterial udder infection. PMID- 26805970 TI - Reduced-fat dried distillers grains with solubles reduces the risk for milk fat depression and supports milk production and ruminal fermentation in dairy cows. AB - Twenty Holstein cows, 12 primiparous and 8 multiparous, with (mean +/- SD) 91 +/- 19 d in milk and 595 +/- 81 kg were used in replicated 4 * 4 Latin squares to compare the effects of feeding conventional dried distillers grains with solubles (DDGS) and reduced-fat DDGS (RFDDGS) in combination with rumen-inert fat (RIF) on milk production and rumen fermentation; one square contained rumen cannulated animals for rumen measurements. In each 21-d period, cows were randomly assigned to 1 of 4 dietary treatments (values on a dry matter basis): (1) control (CON) that contained 0% DDGS; (2) DG contained 30% DDGS; (3) RFDG contained 30% RFDDGS in substitution of DDGS; and (4) RFDG+RIF was similar to RFDG with the addition of 1.9% RIF. Unlike most practical diets in the dairy field, our diets had <22% forage neutral detergent fiber and >18.0% crude protein. Dry matter intake was similar across treatments with any form of DDGS averaging 26.0 +/- 0.6 kg/d, whereas the CON diet resulted in less dry matter intake, 21.6 +/- 0.6 kg/d. Milk yield tended to be 1.7 kg/d greater for diets with either type of DDGS. Concentration of milk protein was greatest for the DG and RFDG diets, intermediate for the RFDG+RIF diet, and least for the CON diet, namely 3.22, 3.21, 3.12, and 3.07 +/- 0.05%. Reduced milk fat percentage and yield were observed when cows consumed the DG diet, 3.27 +/- 0.10% and 1.11 +/- 0.04 kg/d, respectively, whereas these responses were similar among CON, RFDG, and RFDG+RIF, which averaged 3.68 +/- 0.10% and 1.22 +/- 0.04 kg/d. The presence of trans 10,cis-12 conjugated linoleic acid was only detected in milk from cows consuming the DG diet; similarly, concentration and yield of trans-10 18:1 were greater for cows consuming this diet. Rumen ammonia was similar across treatments averaging 27.0 +/- 2.1mg/dL. The CON and RFDG+RIF diets had similar mean pH, 6.1 +/- 0.11, whereas DG and RFDG resulted in lower pH averaging 5.79 +/- 0.11. No effect on total concentration of volatile fatty acids was observed; the overall mean was 121 +/- 4.11 mM; molar proportion of acetate was affected by treatment resulting in 67.3, 63.2, 61.4, and 60.9 +/- 0.93 mol/100 mol for CON, RFDG+RIF, RFDG, and DG, respectively. Results from DNA sequencing showed that rumen bacterial community structure was relatively stable with minor changes at the family and genus levels; these changes may be associated with low starch diets, and hence reduced amylolytic bacteria populations. Feeding high proportions of RFDDGS resulted in greater dry matter intake with low risk for milk fat depression while supporting ruminal fermentation. PMID- 26805971 TI - Individual responses of dairy cows to a 24-hour milking interval. AB - Some dairy farmers opt to omit one milking, either incidentally or weekly, without changing other milking times. This practice entails an extended milking interval of 24h (24h-MI), which is associated with a decrease in milk yield. This decrease varies among cows and could be partly due to factors such as stage of lactation and milk yield level. The aim of this study was to describe the average and individual responses in terms of loss and carryover effects of a 24h-MI on milk yield. The influence of factors such as parity, stage of lactation, and milk yield potential were investigated, together with response repeatability. Our trial used 292 Holstein-Friesian cows, and consisted of 3 successive periods: 1 wk of twice-daily milking (TDM) as a control, one 24h-MI, and then 13d of TDM. The number of observations per cow ranged from 1 to 9, with no more than three 24h-MI per lactation. The 24h-MI reduced milk yield by 23% (7.8 kg on average) and milk lactose content by 2.6g/kg on the 24h-MI day. Milk fat and protein content, and somatic cell score increased by 3.0 g/kg, 0.5 g/kg, and 0.4 units, respectively. No significant carryover effect was found of a 24h-MI on milk yield or milk composition 2 wk after resumption of TDM. Milk yield loss and recovery varied widely (coefficient of variation 62%), and the relationship between milk loss and milk recovery showed substantial variation (residual standard deviation 2.1 kg/d). Cows with a greater milk potential level lost more milk yield but recovered more milk, with no influence on recovery:loss ratio. Cows in early lactation recovered the lost milk yield faster. Repeatability of the responses to a 24h-MI was 44% for milk yield loss (kg/d), 57% for relative milk yield loss (%), 33% for milk yield recovery (kg/d), and 0% for milk recovery:loss ratio (%), suggesting a genetically determined ability to limit loss when one milking is omitted. To conclude, a 24h-MI caused higher milk yield losses than reported in previous studies. Stage of lactation, estimated potential milk yield level, and parity explained the cows' response to the 24h-MI, but did not account for all the individual variability. PMID- 26805972 TI - Short communication: Methicillin-resistant Staphylococcus aureus in bulk tank milk of dairy cows and effect of swine population density. AB - The methicillin-resistant Staphylococcus aureus (MRSA) has recently frequently been reported in dairy cattle, usually with low prevalence. The livestock associated MRSA (LA-MRSA) ST398 is especially involved in cases of subclinical and clinical mastitis. Swine carry LA-MRSA without clinical symptoms and are considered its reservoir and shedder. People exposed to swine are particularly at risk of LA-MRSA colonization. Environments with relevant livestock density are a demonstrated risk factor for humans to be carriers of a LA-MRSA. This work investigated dairy farms located in an area with a high livestock density, mainly represented by swine. Bulk tank milk samples from 224 dairy farms were collected, and their status was defined as MRSA-positive or MRSA-negative based on culture on chromogenic medium. The number of fattening swine and of fattening swine herds was calculated in an area of 3 km around each dairy farm through georeferencing. The probability of a Staphylococcus aureus-positive dairy farm to be MRSA positive based on the extent of potential infective pressure due to swine density was calculated. Both the number of swine herds and the number of swine were associated with the MRSA status of dairy herds. The 9 MRSA isolated were typed by multi-locus sequence typing and spa-typing, and characterized for their virulence factors and antimicrobial resistance profiles. The ST and spa-types detected are consistent with those present in the Italian swine population. Virulence and resistance profiles are mostly consistent with the types detected. This work provides the first evidence of the epidemiological challenge exerted by the density of the swine population on MRSA in dairy cows. PMID- 26805973 TI - Short communication: Electrospinning of casein/pullulan blends for food-grade applications. AB - Electrospinning is a complex process that produces fibers with diameters on the micrometer or nano-scale from an electrified jet of a polymer solution. The objective of this study was to create electrospun fibers for food use from aqueous solutions of calcium (CaCAS) or sodium caseinate (NaCAS). Fibers were not formed from electrospinning of solutions of either caseinate (CAS) at 50 degrees C, but were formed from blends of either CAS solution with aqueous solutions of the food-grade polysaccharide, pullulan (PUL), when using mass ratios from 2:1 to 1:4 of PUL/CAS. The CAS in the spinning solutions ranged from 3 to 15% (wt/wt) and the PUL ranged from 5 to 15% (wt/wt). The PUL/CaCAS 1:2 fibers showed the lowest fiber diameter sizes (FDS) of 172 +/- 43 nm, as determined by scanning electron microscopy, and were smaller in size than fibers electrospun from 15% (wt/wt) PUL solution. The PUL/NaCAS solutions were more viscous and formed fibers with occasional branching and less uniform FDS at higher NaCAS contents. Reductions in NaCAS in these solutions reduced viscosity and improved jet stabilities with consequent improvement in fiber morphology leading to more uniform FDS. Fibers with less defects and more homogeneous FDS were formed from PUL/CaCAS blends with more CaCAS, showing that each CAS interacted differently with PUL and formed the best fibers at different solution conditions. Calcium bridging may also underlie the anomalous behavior of the PUL/CaCAS blends by forming crosslinks with the phosphoserine residues, further enabling chain entanglements for fiber formation. The PUL/NaCAS fibers tended to be larger than the PUL/CaCAS fibers, which may also be due to other factors such as solution surface tension and conductivity, which also affect fiber quality and size. The shear viscosities at 100 s(-1) of the solutions producing fibers were within the range of 0.07 to 0.16 Pa/s, with the smallest standard deviations in FDS noted for solutions with viscosities within about 25% that of PUL. This is the first example of caseinate fibers prepared using a food-grade carrier rendering a product with potential use in food and packaging applications. PMID- 26805974 TI - Evaluation of probiotic properties of Lactobacillus plantarum WLPL04 isolated from human breast milk. AB - Lactobacillus plantarum WLPL04, a specific strain isolated from human breast milk, was investigated for its survival capacity (acid and bile salt tolerance, survival in simulated gastrointestinal tract, inhibition of pathogens, antibiotic susceptibility, yield of exopolysaccharides) and probiotic properties (antiadhesion of pathogens, protection from harmful effect of sodium dodecyl sulfate, and antiinflammatory stress on Caco-2 cells). The results showed that Lb. plantarum WLPL04 had broad-spectrum activity against gram-positive strains (Listeria monocytogenes CMCC54007, Bacillus cereus ATCC14579, and Staphylococcus aureus CMCC26003) and gram-negative strains (Pseudomonas aeruginosa MCC10104, Shigella sonnei ATCC25931, Enterobacter sakazakii ATCC29544, Salmonella typhimurium ATCC13311, and Escherichia coli O157:H7). Antibiotic susceptibility tests showed that Lb. plantarum WLPL04 was susceptible to 8 of 14 antibiotics (e.g., erythromycin and nitrofurantoin) and resistant to 6 of 14 antibiotics (e.g., kanamycin and bacitracin). Lactobacillus plantarum WLPL04 was able to survive at pH 2.5 for 3h and at 0.45% bile salt for 12h, suggesting that it can survive well in the gastrointestinal tract. In addition, the exopolysaccharide yield of Lb. plantarum WLPL04 reached 426.73 +/- 65.56 mg/L at 24h. With strategies of competition, inhibition, and displacement, Lb. plantarum WLPL04 reduced the adhesion of E. coli O157:H7 (35.51%), Sal. typhimurium ATCC 13311 (8.10%), and Staph. aureus CMCC 26003 (40.30%) on Caco-2 cells by competition, and subsequently by 59.80, 62.50, and 42.60%, respectively, for the 3 pathogens through inhibition, and by 75.23, 39.97, and 52.88%, respectively, through displacement. Lactobacillus plantarum WLPL04 attenuated the acute stress induced by sodium dodecyl sulfate on Caco-2 cells and significantly inhibited the expression of inflammatory cytokines (IL-6, IL-8 and tumor necrosis factor-alpha) on Caco-2 cells but increased IL-10 expression in vitro compared with the Salmonella-treated group. In summary, Lb. plantarum WLPL04 from breast milk could be considered as a probiotic candidate for dairy products to promote human health. PMID- 26805975 TI - Effects of fractionated colostrum replacer and vitamins A, D, and E on haptoglobin and clinical health in neonatal Holstein calves challenged with Mycobacterium avium ssp. paratuberculosis. AB - Thirty Holstein calves were obtained from 2 dairy farms in central Iowa at birth and randomly assigned to 1 of 6 treatment groups: (1) colostrum deprived (CD), no vitamins; (2) colostrum replacer (CR), no vitamins; (3) CR, vitamin A; (4) CR, vitamin D3; (5) CR, vitamin E; and (6) CR, vitamins A, D3, E, with 5 calves per treatment in a 14-d study. Calves were fed pasteurized whole milk (CD) or fractionated colostrum replacer (CR) at birth (d 0) and injected with vitamins according to treatment group. From d 1 through d 14 of the study, all calves were fed pasteurized whole milk (PWM) supplemented with vitamins as assigned. All calves were inoculated with Mycobacterium avium ssp. paratuberculosis on d 1 and 3 of age. Calves fed CR acquired IgG1 and haptoglobin in serum within 24 h of birth, whereas CD calves did not. The CR-fed calves were 2.5 times less likely to develop scours, and CR calves supplemented with vitamins D3 and E also demonstrated a decreased incidence of scours. Serum vitamin levels of A, D, and E increased within treatment group by d 7 and 14 of the study. Interestingly, synergistic effects of supplemental vitamins A, D3, and E on serum 25-(OH) vitamin D were observed at d 7, resulting in higher levels than in calves administered vitamin D only. Further, vitamin D3 deficiency was observed in CD and CR calves fed a basal diet of pasteurized whole milk and no supplemental vitamins. Colonization of tissues with Mycobacterium avium ssp. paratuberculosis was negligible and was not affected by colostrum feeding or vitamin supplementation. Results demonstrated passive transfer of haptoglobin to neonatal calves, and potential health benefits of supplemental vitamins D3 and E to calves fed pasteurized whole milk. PMID- 26805976 TI - Effect of incorporation of antioxidants on the chemical, rheological, and sensory properties of probiotic petit suisse cheese. AB - This work investigated the effect of the addition of different antioxidants (ascorbic acid, glucose oxidase, cysteine, and jabuticaba extract) on the rheological and sensorial properties of the probiotic petit suisse cheese. Absence of influence of the antioxidants at the physico-chemical characteristics of the petit suisse cheese was observed. Overall, the petit suisse cheeses presented weak gel characteristics and behaved as pseudoplastic material, except for control. All treatments exhibited a thixotropic non-Newtonian behavior; however, higher hysteresis area was obtained for control sample, which indicates that antioxidants incorporated to petit suisse had a protective effect on the typical thixotropic behavior of the Quark gel. The commercial sample presented higher scores for all aspects by consumers, whereas the probiotic petit suisse samples presented opposite behavior. Projective mapping was able to generate a vocabulary where the sample containing jabuticaba skin extract obtained by supercritical extraction was characterized by the panelists as presenting grape flavor and purple color. PMID- 26805977 TI - Technical note: A method for isolating glycogen granules from ruminal protozoa for further characterization. AB - Evaluation of physical, chemical, and enzymatic hydrolysis characteristics of protozoal glycogen is best performed on a pure substrate to avoid interference from other cell components. A method for isolating protozoal glycogen granules without use of detergents or other potentially contaminating chemicals was developed. Rumen inoculum was incubated anerobically in vitro with glucose. Glycogen-laden protozoa produced in the fermentation, primarily isotrichids, were allowed to sediment in a separatory funnel and were dispensed. The protozoa were processed through repeated centrifugations and sonication to isolate glycogen granules largely free of feed and cellular debris. The final water-insoluble lyophilized product analyzed as 98.3% alpha-glucan with very rare starch granules and 1.9% protein. Observed losses of glycogen granules during the clean-up process indicate that this procedure should not be used for quantitative assessment of protozoal glycogen from fermentations. Further optimization of this procedure to enhance the amount of glycogen obtained per fermentation may be possible. PMID- 26805978 TI - Heritability estimates for enteric methane emissions from Holstein cattle measured using noninvasive methods. AB - The objective of this study was to estimate heritability of enteric methane emissions from dairy cattle. Methane (CH4) and CO2 were measured with a portable air-sampler and analyzer unit based on Fourier transform infrared detection. Data were collected on 3,121 Holstein dairy cows from 20 herds using automatic milking systems. Three CH4 phenotypes were acquired: the ratio between CH4 and CO2 in the breath of the cows (CH4_RATIO), the estimated quantified amount of CH4 (in g/d) measured over a week (CH4_GRAMSw), and CH4 intensity, defined as grams of CH4 per liter of milk produced (CH4_MILK). Fat- and protein-corrected milk (FPCM) and live weight data were also derived for the analysis. Data were analyzed using several univariate and bivariate linear animal models. The heritability of CH4_GRAMSw and CH4_MILK was 0.21 with a standard error of 0.06, and the heritability of CH4_RATIO was 0.16 with a standard error of 0.04. The 2 CH4 traits CH4_GRAMSw and CH4_RATIO were genetically highly correlated (rg=0.83) and they were strongly correlated with FPCM, meaning that, in this study, a high genetic potential for milk production will also mean a high genetic potential for CH4 production. The genetic correlation between CH4_MILK and FPCM and live weight showed similar patterns as the other CH4 phenotypes, although the correlations in general were closer to zero. The genetic correlations between the 3 CH4 phenotypes and live weight were low and only just significantly different from zero, meaning there is less indication of a genetic relationship between CH4 emission and live weight of the cow. None of the residual correlations between the ratio of CH4 and CO2, CH4 production in grams per day, FPCM, and live weight were significantly different from zero. The results from this study suggest that CH4 emission is partly under genetic control, that it is possible to decrease CH4 emission from dairy cattle through selection, and that selection for higher milk yield will lead to higher genetic merit for CH4 emission/cow per day. PMID- 26805979 TI - Two approaches to improve fertility of subclinical mastitic dairy cows. AB - Mastitis, particularly in its subclinical form, is a widely spread disease that reduces the fertility of lactating cows. A major cause of poor conception risk has been associated with delayed ovulation of a large subgroup of subclinical mastitic cows. This study examined 2 approaches to improve fertility in this subgroup. Subclinical mastitic cows were defined by somatic cell count elevated above a threshold of 150,000 cells/mL of milk determined in all monthly test day samples collected before AI. Uninfected (control) cows were defined by somatic cell count below threshold. In experiment 1, we examined a hormonal approach aimed to correct the timing of ovulation in mastitic cows in which it would otherwise be delayed. The probability of conception of mastitic and uninfected groups following Ovsynch (OVS) and timed AI versus AI following detected estrus (E) was examined (n=1,553 AI) and analyzed by a multivariable, logistic model statement using the GLIMMIX procedure of SAS. The OVS protocol significantly elevated the probability of conception of mastitic cows to a level similar to that of their uninfected counterparts. Actual mean conception risks for uninfected-E, subclinical-E, uninfected-OVS, and subclinical-OVS groups were 41.8, 26.4, 39.3, and 40.5%, respectively. The OVS protocol did not improve probability of conception in cows diagnosed with uterine disease postpartum. In experiment 2, a management approach aimed to better synchronize timing of ovulation with timing of AI in subclinical mastitic cows was examined. A second AI was added 24h after the first (routine) AI, following detection of natural estrus. Probability of conception did not differ between subclinical mastitic cows inseminated once or twice. Lack of improvement in conception risk might be related to low preovulatory LH surge in mastitic cows, which is likely to induce not only delayed ovulation but also disruption of oocyte maturation. Thus the OVS protocol can improve fertility of subclinical mastitic cows, probably due to "corrected" timing of ovulation in cows in which it would otherwise be delayed. PMID- 26805980 TI - Short communication: Effect of storage temperature on the solubility of milk protein concentrate 80 (MPC80) treated with NaCl or KCl. AB - A previous study in our laboratory showed that addition of 150 mM NaCl or KCl into diafiltration water improved the solubility of freshly made milk protein concentrate 80 (MPC80). In the present study, the objectives were (1) to evaluate the solubility of NaCl- or KCl-treated MPC80 samples kept at varying temperatures and then stored for extensive periods at room temperature (21 degrees C +/- 1 degrees C); and (2) to determine if MPC80 samples stored at different temperatures and protein conformation can be grouped or categorized together. Freshly manufactured MPC80 samples were untreated (control), processed with NaCl, or processed with KCl. One set of sample bags was stored at 4 degrees C; second and third sets of bags were kept at 25 degrees C and 55 degrees C for 1 mo (31 d) and then transferred to room temperature (21 degrees C +/- 1 degrees C) storage conditions for 1 yr (365 d). Samples were tested for nitrogen solubility index (NSI) and for protein changes by Fourier-transform infrared (FTIR) spectroscopy. Analysis of variance results for NSI showed 2 significantly different groupings of MPC80 samples. The more soluble group contained samples treated with NaCl or KCl and stored at either 4 degrees C or 25 degrees C. These samples had mean NSI >97.5%. The less soluble groups contained all control samples, regardless of storage temperature, and NaCl- or KCl-treated samples stored at 55 degrees C. These samples had mean NSI from 39.5 to 58%. Within each of these groups (more soluble and less soluble), no significant differences in solubility were detected. Pattern recognition analysis by soft independent modeling of class analogy (SIMCA) was used to assess protein changes during storage by monitoring the amide I and amide II (1,700(-1) to 1,300 cm(-1)) regions. Dominant bands were observed at 1,385 cm(-1) for control, 1,551 cm(-1) for KCl-treated samples, and 1,694 cm(-1) for NaCl-treated samples. Moreover, SIMCA clustered the MPC80 samples stored at 4 degrees C separately from samples stored at 25 degrees C and 55 degrees C. This study demonstrates that (1) the addition of NaCl or KCl during MPC80 manufacture reduces the deleterious changes in solubility upon prolonged storage at 4 degrees C or 25 degrees C, and (2) the solubility of samples stored at 55 degrees C is poor irrespective of salt treatment. PMID- 26805981 TI - Nonambulatory cows: Duration of recumbency and quality of nursing care affect outcome of flotation therapy. AB - Cows that are unable or unwilling to stand and remain recumbent for >= 12 h are defined as nonambulatory. Care and management of nonambulatory cattle is considered a major animal welfare concern facing the livestock industry, particularly the dairy sector. Flotation therapy has gained interest as a means to promote recovery in nonambulatory cows and is based on the concept that by floating the cow in warm water, secondary pressure damage to muscles and nerves will be reduced. The objective of this study was to assess the physiological responses to stress related to the flotation therapy and to evaluate the effect of recumbency duration and nursing care on the outcome of the flotation therapy. The outcomes of 34 nonambulatory Holstein dairy cows were analyzed after they were subjected to flotation therapy. The duration of recumbency and quality of nursing care provided before initiation of the flotation treatment were assessed based on producer responses to survey questions, and from on-site observations by the researchers. A veterinarian examined all cows before flotation therapy began. The treatment was divided into 5 phases: baseline (before filling), manipulation (placing the cow into the tank), filling (the tank was filled with water), flotation (the cow was confined in the filled tank), and draining (water was removed from the tank). Stress responses to the procedure, excluding the manipulation portion, were assessed using heart rate variability. The high frequency component (HF normalized units) decreased during the filling and draining phases (2.8 +/- 0.2 and 3.1 +/- 0.4, respectively) compared with the baseline and floating phase (5.1 +/- 0.6 and 4.9 +/- 0.3, [corrected] respectively). These results indicate that the stress related to the flotation therapy is greatest during the filling and draining phases of the treatment, when cows likely have to exert increased effort to transition to a standing position. The flotation therapy was less likely to be successful on cows that had been recumbent for longer periods (odds ratio=0.96; 95% CI=0.93-0.99, for every 1-h increase in time recumbent before the therapy began). Higher quality of nursing care provided to nonambulatory cows increased the chance of recovery. In conclusion, cows subjected to flotation therapy were more likely to recover if they were treated at early stage of recumbency and if good nursing care was provided while recumbent. PMID- 26805982 TI - Associations between lying behavior and lameness in Canadian Holstein-Friesian cows housed in freestall barns. AB - Lying behavior is an important measure of comfort and well-being in dairy cattle, and changes in lying behavior are potential indicators and predictors of lameness. Our objectives were to determine individual and herd-level risk factors associated with measures of lying behavior, and to evaluate whether automated measures of lying behavior can be used to detect lameness. A purposive sample of 40 Holstein cows was selected from each of 141 dairy farms in Alberta, Ontario, and Quebec. Lying behavior of 5,135 cows between 10 and 120 d in milk was automatically and continuously recorded using accelerometers over 4 d. Data on factors hypothesized to influence lying behavior were collected, including information on individual cows, management practices, and facility design. Associations between predictor variables and measures of lying behavior were assessed using generalized linear mixed models, including farm and province as random and fixed effects, respectively. Logistic regression models were used to determine whether lying behavior was associated with lameness. At the cow-level, daily lying time increased with increasing days in milk, but this effect interacted with parity; primiparous cows had more frequent but shorter lying bouts in early lactation, changing to mature-cow patterns of lying behavior (fewer and longer lying bouts) in late lactation. In barns with stall curbs >22 cm high, the use of sand or >2 cm of bedding was associated with an increased average daily lying time of 1.44 and 0.06 h/d, respectively. Feed alleys >= 350 cm wide or stalls >= 114 cm wide were associated with increased daily lying time of 0.39 and 0.33 h/d, respectively, whereas rubber flooring in the feed alley was associated with 0.47 h/d lower average lying time. Lame cows had longer lying times, with fewer, longer, and more variable duration of bouts compared with nonlame cows. In that regard, cows with lying time >= 14 h/d, <= 5 lying bouts per day, bout duration >= 110 min/bout, or standard deviations of bout duration over 4 d >= 70 min had 3.7, 1.7, 2.5, and 3.0 higher odds of being lame, respectively. Factors related to comfort of lying and standing surfaces significantly affected lying behavior. Finally, we inferred that automated measures of lying behavior could contribute to lameness detection, especially when interpreted in the context of other factors known to affect lying behavior, including those associated with the individual cow (e.g., parity and stage of lactation) or environment (e.g., stall surface). PMID- 26805983 TI - Effect of milk replacer program on calf performance and digestion of nutrients with age of the dairy calf. AB - Calves fed large amounts of milk replacer (MR) gain more body weight preweaning than calves fed less-aggressive programs; however, postweaning growth may be reduced. Limited research suggests that less than optimal digestion of the postweaned diet due to large amounts of MR with reduced dry feed intake preweaning may contribute to growth impairment postweaning. Current research was conducted to compare growth and postweaning digestion in 3-d-old male Holstein calves fed various MR programs. The MR programs were a conventional [CON; 0.44 kg of dry matter (DM) 21% crude protein (CP), 21% fat powder fed for 42d], moderate (MOD; 0.66 kg of DM 27% CP, 17% fat powder fed for 42d), and aggressive program (AGG; up to 0.87 kg of DM 27% CP, 17% fat powder fed for 49d). All calves were fed a 20% CP textured starter and water ad libitum for 56d. The trial used 96 calves (initially 41 +/- 1.9 kg of body weight) received 5 wk apart in 2 groups of 48 calves. During d 51 to 56, fecal samples were collected from 5 calves per treatment randomly selected from calves in the first group. Selected nutrients and acid-insoluble ash (used as an internal flow marker) were analyzed in the starter and feces to estimate digestibility. Data were analyzed as a randomized complete block design with starting time of each group of calves as a block. Repeated measure analysis was performed on overall (0 to 56d) data. Means were separated with a protected least significant difference test. Pen was the experimental unit. Calves fed CON had the least average daily gain [CON=0.35, MOD=0.51, and AGG=0.55 kg/d; standard error of the mean (SEM)=0.018], feed efficiency (CON=0.35, MOD=0.49, and AGG=0.48 gain/feed, SEM=0.016), and change in hip width (CON=3.3, MOD=4.1, and AGG=4.1cm, SEM=0.20) compared with calves fed other programs. Calves fed AGG had the greatest change in BCS and least starter intake compared with calves fed the other programs. Digestibility of organic matter was 79, 78, and 68% and neutral detergent fiber was 54, 51, and 26% for calves fed programs CON, MOD, and AGG, respectively, and were least for calves fed AGG. These results indicate that postweaning digestion is lower than optimal and contributes to lower postweaning growth in calves fed aggressive compared with conventional or moderate MR programs. PMID- 26805984 TI - A novel behavioral model of the pasture-based dairy cow from GPS data using data mining and machine learning techniques. AB - A better understanding of the behavior of individual grazing dairy cattle will assist in improving productivity and welfare. Global positioning systems (GPS) applied to cows could provide a means of monitoring grazing herds while overcoming the substantial efforts required for manual observation. Any model of behavioral prediction using GPS needs to be accurate and robust by accounting for inter-cow variation as well as atmospheric effects. We evaluated the performance using a series of machine learning algorithms on GPS data collected from 40 pasture-based dairy cows over 4 mo. A feature extraction step was performed on the collected raw GPS data, which resulted in 43 different attributes. The evaluated behaviors were grazing, resting, and walking. Classifier learners were built using 10 times 10-fold cross validation and tested on an independent test set. Results were evaluated using a variety of statistical significance tests across all parameters. We found that final model selection depended upon level of performance and model complexity. The classifier learner deemed most suitable for this particular problem was JRip, a rule-based learner (classification accuracy=0.85; false positive rate=0.10; F-measure=0.76; area under the receiver operating curve=0.87). This model will be used in further studies to assess the behavior and welfare of pasture-based dairy cows. PMID- 26805985 TI - Compromised Lactobacillus helveticus starter activity in the presence of facultative heterofermentative Lactobacillus casei DPC6987 results in atypical eye formation in Swiss-type cheese. AB - Nonstarter lactic acid bacteria are commonly implicated in undesirable gas formation in several varieties, including Cheddar, Dutch-, and Swiss-type cheeses, primarily due to their ability to ferment a wide variety of substrates. This effect can be magnified due to factors that detrimentally affect the composition or activity of starter bacteria, resulting in the presence of greater than normal amounts of fermentable carbohydrates and citrate. The objective of this study was to determine the potential for a facultatively heterofermentative Lactobacillus (Lactobacillus casei DPC6987) isolated from a cheese plant environment to promote gas defects in the event of compromised starter activity. A Swiss-type cheese was manufactured, at pilot scale and in triplicate, containing a typical starter culture (Streptococcus thermophilus and Lactobacillus helveticus) together with propionic acid bacteria. Lactobacillus helveticus populations were omitted in certain vats to mimic starter failure. Lactobacillus casei DPC6987 was added to each experimental vat at 4 log cfu/g. Cheese compositional analysis and X-ray computed tomography revealed that the failure of starter bacteria, in this case L. helveticus, coupled with the presence of a faculatively heterofermentative Lactobacillus (L. casei) led to excessive eye formation during ripening. The availability of excess amounts of lactose, galactose, and citrate during the initial ripening stages likely provided the heterofermentative L. casei with sufficient substrates for gas formation. The accrual of these fermentable substrates was notable in cheeses lacking the L. helveticus starter population. The results of this study are commercially relevant, as they demonstrate the importance of viability of starter populations and the control of specific nonstarter lactic acid bacteria to ensure appropriate eye formation in Swiss-type cheese. PMID- 26805986 TI - Lactose in milk replacer can partly be replaced by glucose, fructose, or glycerol without affecting insulin sensitivity in veal calves. AB - Calf milk replacer (MR) contains 40 to 50% lactose. Lactose strongly fluctuates in price and alternatives are desired. Also, problems with glucose homeostasis and insulin sensitivity (i.e., high incidence of hyperglycemia and hyperinsulinemia) have been described for heavy veal calves (body weight >100 kg). Replacement of lactose by other dietary substrates can be economically attractive, and may also positively (or negatively) affect the risk of developing problems with glucose metabolism. An experiment was designed to study the effects of replacing one third of the dietary lactose by glucose, fructose, or glycerol on glucose homeostasis and insulin sensitivity in veal calves. Forty male Holstein-Friesian (body weight=114 +/- 2.4 kg; age=97 +/- 1.4 d) calves were fed an MR containing 462 g of lactose/kg (CON), or an MR in which 150 g of lactose/kg of MR was replaced by glucose (GLU), fructose (FRU), or glycerol (GLY). During the first 10d of the trial, all calves received CON. The CON group remained on this diet and the other groups received their experimental diets for a period of 8 wk. Measurements were conducted during the first (baseline) and last week of the trial. A frequently sampled intravenous glucose tolerance test was performed to assess insulin sensitivity and 24 h of urine was collected to measure glucose excretion. During the last week of the trial, a bolus of 1.5 g of [U-(13)C] substrates was added to their respective meals and plasma glucose, insulin, and (13)C-glucose responses were measured. Insulin sensitivity was low at the start of the trial and remained low [1.2 +/- 0.1 and 1.0 +/- 0.1 (mU/L)(-1) * min(-1)], and no treatment effect was noted. Glucose excretion was low at the start of the trial (3.4 +/- 1.0 g/d), but increased in CON and GLU calves (26.9 +/- 3.9 and 43.0 +/- 10.6g/d) but not in FRU and GLY calves. Postprandial glucose was higher in GLU, lower in FRU, and similar in GLY compared with CON calves. Postprandial insulin was lower in FRU and GLY and similar in GLU compared with CON calves. Postprandial (13)C-glucose increased substantially in FRU and GLY calves, indicating that calves are able to partially convert these substrates to glucose. We concluded that replacing one third of lactose in MR by glucose, fructose, or glycerol in MR differentially influences postprandial glucose homeostasis but does not affect insulin sensitivity in veal calves. PMID- 26805987 TI - Implementation of genomic recursions in single-step genomic best linear unbiased predictor for US Holsteins with a large number of genotyped animals. AB - The objectives of this study were to develop and evaluate an efficient implementation in the computation of the inverse of genomic relationship matrix with the recursion algorithm, called the algorithm for proven and young (APY), in single-step genomic BLUP. We validated genomic predictions for young bulls with more than 500,000 genotyped animals in final score for US Holsteins. Phenotypic data included 11,626,576 final scores on 7,093,380 US Holstein cows, and genotypes were available for 569,404 animals. Daughter deviations for young bulls with no classified daughters in 2009, but at least 30 classified daughters in 2014 were computed using all the phenotypic data. Genomic predictions for the same bulls were calculated with single-step genomic BLUP using phenotypes up to 2009. We calculated the inverse of the genomic relationship matrix GAPY(-1) based on a direct inversion of genomic relationship matrix on a small subset of genotyped animals (core animals) and extended that information to noncore animals by recursion. We tested several sets of core animals including 9,406 bulls with at least 1 classified daughter, 9,406 bulls and 1,052 classified dams of bulls, 9,406 bulls and 7,422 classified cows, and random samples of 5,000 to 30,000 animals. Validation reliability was assessed by the coefficient of determination from regression of daughter deviation on genomic predictions for the predicted young bulls. The reliabilities were 0.39 with 5,000 randomly chosen core animals, 0.45 with the 9,406 bulls, and 7,422 cows as core animals, and 0.44 with the remaining sets. With phenotypes truncated in 2009 and the preconditioned conjugate gradient to solve mixed model equations, the number of rounds to convergence for core animals defined by bulls was 1,343; defined by bulls and cows, 2,066; and defined by 10,000 random animals, at most 1,629. With complete phenotype data, the number of rounds decreased to 858, 1,299, and at most 1,092, respectively. Setting up GAPY(-1) for 569,404 genotyped animals with 10,000 core animals took 1.3h and 57 GB of memory. The validation reliability with APY reaches a plateau when the number of core animals is at least 10,000. Predictions with APY have little differences in reliability among definitions of core animals. Single-step genomic BLUP with APY is applicable to millions of genotyped animals. PMID- 26805988 TI - Short communication: Multi-trait estimation of genetic parameters for milk protein composition in the Danish Holstein. AB - Genetic parameters were estimated for the major milk proteins using bivariate and multi-trait models based on genomic relationships between animals. The analyses included, apart from total protein percentage, alphaS1-casein (CN), alphaS2-CN, beta-CN, kappa-CN, alpha-lactalbumin, and beta-lactoglobulin, as well as the posttranslational sub-forms of glycosylated kappa-CN and alphaS1-CN-8P (phosphorylated). Standard errors of the estimates were used to compare the models. In total, 650 Danish Holstein cows across 4 parities and days in milk ranging from 9 to 481d were selected from 21 herds. The multi-trait model generally resulted in lower standard errors of heritability estimates, suggesting that genetic parameters can be estimated with high accuracy using multi-trait analyses with genomic relationships for scarcely recorded traits. The heritability estimates from the multi-trait model ranged from low (0.05 for beta CN) to high (0.78 for kappa-CN). Genetic correlations between the milk proteins and the total milk protein percentage were generally low, suggesting the possibility to alter protein composition through selective breeding with little effect on total milk protein percentage. PMID- 26805989 TI - Effects of late-gestation heat stress on immunity and performance of calves. AB - Lactating cows that experience heat stress will have reduced dry matter intake and milk yield and shift metabolism, which ultimately reduces the efficiency of milk production. Dry cows that are heat stressed similarly experience lower intake, reduced mammary growth, and compromised immune function that ultimately results in a poorer transition into lactation and lower milk yield in the next lactation. A recent focus in our laboratory is on the effects of late gestation, in utero heat stress on calf survival and performance. We have completed a series of studies to examine preweaning growth and health, and later reproductive and productive responses, in an attempt to quantify acute and persistent effects of in utero heat strain. Late gestation heat stress results in calves with lower body weight at birth, shorter stature at weaning, and failure to achieve the same weight or height at 12 mo of age observed in calves from dams that are cooled when dry. A portion of the reduced growth may result from the lower immune status observed in calves heat stressed in utero, which begins with poorer apparent efficiency of immunoglobulin absorption and extends to lower survival rates through puberty. Heat-stressed calves, however, have permanent shifts in metabolism that are consistent with greater peripheral accumulation of energy and less lean growth relative to those from cooled dams. Comparing reproductive performance in calves heat stressed versus those cooled in utero, we observe that the cooled heifers require fewer services to attain pregnancy and become pregnant at an earlier age. Tracking the milk production in calves that were heat stressed in utero versus those cooled in late gestation revealed a significant reduction of yield in the first lactation, approximately 5 kg/d through 35 wk of lactation, despite similar body weight and condition score at calving. These observations indicate that a relatively brief period of heat stress in late gestation dramatically alters the health, growth, and ultimate performance of dairy calves. Thus, it is critical to effectively manage heat stress of dry cows to avoid negative effects on the calf. PMID- 26805990 TI - Udder infections with Staphylococcus aureus, Streptococcus dysgalactiae, and Streptococcus uberis at calving in dairy herds with suboptimal udder health. AB - Udder infections with Staphylococcus aureus, Streptococcus dysgalactiae, and Streptococcus uberis are common causes of bovine mastitis. To study these pathogens in early lactation, a 12-mo longitudinal, observational study was carried out in 13 herds with suboptimal udder health. The aims of the study were to investigate the occurrence of these pathogens and to identify if presence of the 3 pathogens, and of genotypes within the pathogens, differed with respect to herd, season, and parity. Quarter milk samples, collected at calving and 4 d in milk (DIM), were cultured for the 3 pathogens. Genotyping of staphylococcal and streptococcal isolates was performed using spa typing and pulsed-field gel electrophoresis, respectively. For each of the 3 pathogens, cows with an udder infection at calving or 4 DIM were allocated to 1 of 4 infection types: cleared (pathogen present only at calving), persistent (pathogen present in the same quarter at calving and 4 DIM), new (pathogen present only at 4 DIM), or cleared/new (pathogen present in 1 quarter at calving and in another quarter at 4 DIM). Associations between season or parity and overall occurrence of pathogens or infection types were determined using univariable mixed-effect logistic regression models and the Fisher's exact test, respectively. The most commonly occurring pathogen was Staph. aureus, followed by Strep. dysgalactiae and Strep. uberis. Persistent infections were the most common infection type among Staph. aureus-infected cows, whereas cleared infections were the most common among Strep. dysgalactiae- and Strep. uberis-positive cows. The proportion of cows with persistent Staph. aureus infections and the proportion of cows having a Strep. uberis infection at calving or 4 DIM were higher in the multiparous cows than in primiparous cows. Infections with Strep. dysgalactiae were less common during the early housing season than during the late housing or pasture seasons, whereas persistent Strep. uberis infections were less common during the pasture season than during the late housing season. The relative occurrence of the 3 pathogens, infection types of each pathogen, and genotype diversity of each pathogen throughout the year or in different seasons and parities varied among the herds, indicating that underlying factors predisposing for udder infections at calving differ between herds. Genotyping of bacterial isolates gave important insight into how such infection patterns differed within and between herds. These findings emphasize the need to choose preventive strategies for each individual herd. PMID- 26805991 TI - Short communication: Influence of labeling on Australian and Chinese consumers' liking of milk with short (pasteurized) and long (UHT) shelf life. AB - Sixty percent of milk consumed in China has a long shelf life (UHT), presumably because milk with a short shelf life (pasteurized) is comparatively expensive. This in contrast to Australia, where 10% of consumed milk is UHT and the price between UHT and pasteurized milk is equivalent. Whether UHT is actually more liked than pasteurized milk by Chinese consumers is unknown. However, the potential positive halo around the expensive pasteurized milk might result in Chinese consumers liking milk more when it is labeled as "short shelf-life milk." To test these hypotheses, Chinese (n=48, 20 males, 28 females, 23 +/- 7.2 yr) and Australian (n=93, 11 males, 82 females, 24 +/- 5.6 yr) consumers tasted and rated (9-point hedonic scale), in a randomized order, 3 * 30-mL samples of UHT milk (labeled as "long shelf-life milk," "short shelf-life milk," or "milk") and 3 * 30-mL samples of pasteurized milk (also labeled as "long shelf-life milk," "short shelf-life milk," or "milk"). Australian participants' liking of milk was not influenced by labeling. Regardless of what the label stated, they always preferred the taste of pasteurized milk over the taste of UHT milk. This was different for Chinese participants, who preferred the taste of UHT milk over the taste of pasteurized milk, but in general had a higher liking for any milk that was labeled "short shelf-life milk." Both Australian and Chinese were more positive about pasteurized than UHT milk. In conclusion, Chinese, but not Australian, consumers' liking of milk was guided by the positive expectations of pasteurized milk and the negative expectations of UHT milk. Further research is needed to investigate if the present findings can be extrapolated to a larger and more varied group of Chinese and Australian consumers. PMID- 26805992 TI - Short communication: Plasma progesterone concentration and ovarian dynamics of lactating Jersey cows treated with 1 or 2 intravaginal progesterone inserts. AB - The objectives of the current experiment were to determine circulating progesterone concentrations and ovarian follicle development of lactating Jersey cows treated with 1 or 2 controlled internal drug release (CIDR) insert containing 1.38 g of progesterone during proestrus. Cows were enrolled in the experiment at 34 +/- 3 d in milk and were paired by parity, body condition score, body weight, and milk yield. Estrous cycles were presynchronized with an injection of GnRH concurrent with a new CIDR insert (study d -7) and 2 injections of PGF2alpha given 5 and 6 d after the GnRH injection (study d -2 and -1, respectively). Cows assigned to the 1CIDR treatment (n=30) or 2CIDR treatment (n=30) received 1 and 2 CIDR inserts, respectively, from study d 0 through 7. Control cows (n=10) did not receive further treatment. On study d -2 and daily from study d 0 through 7, ovaries were examined by transrectal ultrasound and blood samples were collected for determination of progesterone. On study d 7, CIDR inserts were removed after ultrasound exam and blood sample collection. Progesterone concentration from study d 0 through 7 was greatest for 2CIDR cows (2.17 +/- 0.09 ng/mL), followed by 1CIDR cows (1.37 +/- 0.10 ng/mL) and control cows (0.62 +/- 0.21 ng/mL). The interaction between treatment and study day affected progesterone concentration from study d 0 through 7. The average increase in progesterone concentration from study d 1 through 7 was 0.80 ng/mL for 1CIDR and 1.72 ng/mL for 2CIDR cows compared with control cows. The percentage of cows that ovulated between study d 0 and 7 was greatest for control cows (80%), but it did not differ between 1CIDR (12%) and 2CIDR (3.7%) cows. Growth of class III follicles (10-17 mm) identified on study d 0 was affected by treatment because 1CIDR cows had larger class III follicles than 2CIDR cows on study d 5, 6 and 7. A larger proportion of control cows developed a new follicular wave between study d 0 and 7 (control=60.0%, 1CIDR=12.0%, 2CIDR=7.4%). Treatment of lactating Jersey cows with 1 and 2 CIDR inserts resulted in a 1 and 2 fold increase, respectively, in circulating progesterone concentration. Growth class III follicles from cows treated with 2 CIDR inserts was reduced compared with untreated cows and cows treated with 1 CIDR insert. PMID- 26805993 TI - Stress, immunity, and the management of calves. AB - Despite many advances in management and housing of dairy calves, 1 in 10 US dairy heifers die before weaning. A better understanding of the internal and external stimuli that contribute to the physiological and behavioral responses of calves to stressors is needed to reduce the risk of morbidity and mortality. Feeding calves their first meal is crucial, as successful passive transfer reduces the risk of mortality and morbidity. Sexually dimorphic immune and stress responses appear to be present in young cattle, but more research is needed to determine if this is caused by human bias for female calves. After that first feeding, 1 in 10 heifers and most bull calves in the United States are transported to specialized calf-raising facilities, yet information is lacking on the newborn calf stress response during transit. Whether calves are raised on site or at a calf ranch, individual housing systems are commonly used in the United States to reduce the risk of pathogen exposure and provide individual feeding and healthcare. However, health, growth, and social implications may be present for calves in alternative systems with greater space allowance than conventional systems or group housing. Disbudding and castration are typically performed at an early age for dairy calves during the pre-wean stage. These stressors often take place when the calf has decreased passive transfer of Ig and immunity is developing. Availability of pain mitigation through anesthetics and analgesics is limited, but evidence indicates that analgesics attenuate suppressed leukocyte function during these procedures. Solid-feed intake is a primary measure for determining weaning readiness, but some milk replacer formulas may influence the calf's oral behaviors before weaning; therefore, alternate weaning methods may need to coincide with alternate milk replacer formulas. The calf's behavioral and stress response at weaning may influence its immunity during the transition from individual to group housing (commingling). Alternate commingling strategies and nutritional supplements may help with this transition, but more research is needed to explore feasible alternatives. Optimizing the calf's health and well being at these early stages may improve its long-term health and welfare. PMID- 26805994 TI - Seasonality of fertility measured by physical activity traits in Holstein cows. AB - Seasonality of female fertility traits, including the interval from calving to first high activity (CFHA), duration of high activity episode (DHA), and strength of high activity episode (SHA) of first estrus, were studied. The physical activity traits were derived from electronic activity tags for 20,794 Holstein cows in 135 commercial Holstein herds in Denmark. Data were categorized in 3 ways: (1) into 4 seasons of calving: winter (January-March), spring (April-June), summer (July-September), and fall (October-December); (2) into 2 seasons: a cold season (October-March) and a warm season (April-September); and (3) into an increasing light season (IL; January-June), where daylight hours gradually increased, and a decreasing light season (DL; July-December), where daylight hours gradually decreased. At the phenotypic level, least squares means of CFHA were highest at 55d for cows calving in December and lowest at 31d for cows calving in September. The highest least squares means of DHA and SHA were recorded for cows calving in November and lowest for cows calving in May and June. Genetic parameters for all traits were estimated using average information REML in a bivariate animal model that treated the same trait in different calving seasons as different traits. Heritability estimates for CFHA were highest for the winter season (0.13) and low for the other seasons (0.03-0.04), whereas heritability estimates for DHA and SHA were lowest for winter and highest for fall. Heritability estimates for CFHA for the cold season (0.17) was higher than that for the warm season (0.10). Heritability estimates of CFHA for the IL season (0.12) was higher than for the DL season (0.07), but the opposite pattern was found for DHA and SHA. Genetic correlations (rA) of CFHA between winter and summer (rA=0.34 +/- 0.27), and winter and fall (rA=0.65 +/- 0.20) were significantly lower than unity. The corresponding correlations of DHA and SHA between seasons were all close to unity, except for the correlation of SHA between winter and fall (rA=0.36 +/- 0.34). When the year was split into only 2 seasons, the genetic correlation of CFHA between cold and warm seasons was only moderate (rA=0.46 +/- 0.15) but was slightly stronger between IL and DL seasons (rA=0.63 +/- 0.16); both significantly deviated from unity. These results indicate the existence of a genotype by environment interaction for CFHA regardless of calving season classification. PMID- 26805995 TI - Milk yield and estrous behavior during eight consecutive estruses in Holstein cows fed standardized or high energy diets and grouped according to live weight changes in early lactation. AB - Cows managed for extended lactation go through several estruses before rebreeding. The aims of this study were (1) to quantify the effect of the first 8 estruses after calving on milk yield, milking frequency, and estrous behavioral activity, and (2) to determine the effects of early lactation live weight gain (LWG) as an indication of energy balance on milk yield, plasma insulin-like growth factor 1 (IGF-1) concentration, estrous behavioral activity, interval from calving to first estrus, between-estrus intervals, and pregnancy risk. Milk yield, live weight, and estrous behavioral activity were measured daily in 62 Holstein cows, 17 primiparous and 45 multiparous, managed for an 18-mo calving interval. Blood plasma obtained at wk 3, 5, 12, and 24 after calving was analyzed for IGF-1. Estrus was detected by use of milk progesterone profiles combined with visual observations (i.e., mounting behavior and other). The cows were divided into 2 groups: the cows having a negative LWG in each of the first 5 wk postpartum and the cows having a positive LWG in at least 1 of the first 5 wk after calving. The results indicate a similar decrease of 0.56 kg of milk per day of estrus during each of the 8 consecutive estruses. The activity level was 17 +/ 1 movements per hour higher during the 8 estruses compared with the basic activity level. More cows expressed mounting behavior at estrus 8 than at estrus 2 (63.3 and 45.9%, respectively). The negative LWG cows had lower IGF-1 and higher milk production than the positive LWG cows. Both LWG groups had similar interval from calving to first estrus, on average 55 d. To conclude, the decrease in milk yield during estrus is marginal and similar in consecutive estruses. Moreover, estrous behavior is more highly expressed in the later estruses compared with the earlier estruses. Reproductive parameters (frequency of mounting, pregnancy risk, interval to first estrus, and between-estrus intervals) were not influenced by the live weight change during early lactation. PMID- 26805996 TI - Genetic and environmental relationships of different measures of individual cheese yield and curd nutrients recovery with coagulation properties of bovine milk. AB - The aim of this study was to elucidate the relationships between various cheesemaking-related traits, namely the well-known traditional milk coagulation properties (MCP), the new curd firming and syneresis traits, the cheese yield, and the curd nutrient recoveries or whey losses (all measured at the individual level). Data were obtained from 1,167 Brown Swiss cows reared in 85 herds. A 2-L milk sample was collected once from each animal and assessed for 10 phenotypes related to changes in curd firmness (CF) over time, plus 7 cheesemaking traits. The CF-related traits included 4 traditional single-point lactodynamographic properties [rennet coagulation time (RCT, min); time to a CF of 20mm, min; and the CF 30 and 45 min after rennet addition (a30 and a45, respectively)], 4 parameters used to model the 360 CF data recorded over time for each milk sample [the potential asymptotic CF at infinite time (CFP, mm); the CF instant rate constant, % * min(-1); the syneresis instant rate constant, % * min(-1); and the RCT obtained from modeling individual samples], and 2 traits calculated from individual equations [the maximum CF(CFmax, mm); and the time at CFmax, min]. The cheesemaking traits included 3 cheese yield traits (weights of the fresh curd, curd solids and curd moisture as percent of the weights of the processed milk) and 4 milk nutrient recoveries in the curd (calculated as the percent ratios between a given nutrient in the curd versus that in the processed milk). Bayesian methodology-based multivariate analyses were used to estimate the phenotypic, additive genetic, herd/date, and residual relationships between the aforementioned traits, whereas statistical inferences were based on the marginal posterior distributions of the parameters of concern. The a45, CFP, and CFmax traits were genetically associated with all of the percent cheese yield traits (the additive genetic correlations varied from 0.752 to 0.855 for a45; 0.496 to 0.583 for CFP; and 0.750 to 0.801 for CFmax) and the nutrient recovery traits (additive genetic correlations varied from 0.296 to 0.901 for a45; 0.428 to 0.697 for CFP; and 0.412 to 0.941 for CFmax). Moreover, the nutrient recoveries for fat, solids, and energy exhibited large additive genetic correlations with the other coagulation and curd firming traits. In particular, recovery of protein and fat were found to be powerful instruments for understanding the relationships between milk technological properties and cheese quantity or quality. We observed only weak genetic relationships with the milk quality and MCP traits, suggesting that the highly heritable trait of protein recovery should perhaps be included as a genetic index when seeking to improve cheesemaking efficiency at the population level. In contrast, we found that fat recovery exhibited moderate genetic variation and could be improved through the CF over time traits, especially using those recorded during the late phase of the curd firming process. Moreover, our results demonstrated that the traditional MCP have limited relevance for predicting individual cheese yield. Therefore, their use for this purpose in the dairy industry and breeding programs seems questionable. PMID- 26805997 TI - Morphological adaptation of rumen papillae during the dry period and early lactation as affected by rate of increase of concentrate allowance. AB - Knowledge of the morphological adaptation of rumen papilla, which plays an important role in volatile fatty acid absorption, in dry and early lactation dairy cattle is limited. Therefore, macro- and microscopic changes in papilla morphology during the dry period and lactation and the effect of rate of increase of concentrate allowance were studied. Samples were collected from 12 rumen cannulated Holstein Friesian dairy cows during a pretreatment period, 50, 30, and 10 d antepartum (the dry period) and 3 d postpartum (pp), and a treatment period, 9, 16, 30, 44, 60, and 80 d pp. Cows had free access to either a dry period ration [27% grass silage, 27% corn silage, 35% wheat straw, and 11% soybean meal on a dry matter (DM) basis] or a basal lactation ration (42% grass silage, 41% corn silage, and 17% soybean meal on a DM basis, and 0.9 kg of DM/d concentrate). Treatment consisted of either a rapid (1.0 kg of DM/d; RAP; n=6) or gradual (0.25 kg of DM/d; GRAD; n=6) increase of concentrate allowance (up to 10.9 kg of DM/d), starting at d 4 pp, aimed at creating a contrast in rumen-fermentable organic matter (FOM) intake. Papillae were collected from the ventral, ventral blind, and dorsal blind rumen sacs and measured digitally. Intake of DM (11.9 kg/d) and FOM (5.7 kg/d) did not change during the pretreatment period, but increased during the treatment period to 24.5 and 15.0 kg/d at 80 d pp, respectively. Concentrate treatment and sampling day interacted for FOM intake, which was 22% greater in RAP at 16 d pp compared with GRAD. Papilla surface area decreased during the pretreatment period by 19% to 28.0mm(2) at 3 d pp, thereafter increasing to 63.0mm(2) at 80 d pp. Concentrate treatment and sampling day interacted for surface area, which was greater in RAP compared with GRAD at 16 (46.0 vs. 33.2mm(2)), 30 (55.4 vs. 41.2mm(2)), and 44 (60.5 vs. 49.7 mm(2)) days pp, showing that papillae can respond to a rapid rate of increase of FOM intake by increasing growth rate. Microscopic morphology was affected by sampling day, but neither by concentrate treatment nor by their interaction, with a decrease in papilla and epithelium thickness during the lactation. In conclusion, the rumen papillae respond to changes in FOM intake and the magnitude of this response depends on the rate of increase of FOM intake. This response in surface area of the rumen papillae potentially facilitates the absorption of the volatile fatty acids. PMID- 26805998 TI - Effect of concentrate feeding method on the performance of dairy cows in early to mid lactation. AB - The objective of the current study was to determine the effects of concentrate feeding method on milk yield and composition, dry matter (DM) intake (DMI), body weight and body condition score, reproductive performance, energy balance, and blood metabolites of housed (i.e., accommodated indoors) dairy cows in early to mid lactation. Eighty-eight multiparous Holstein-Friesian cows were managed on 1 of 4 concentrate feeding methods (CFM; 22 cows per CFM) for the first 21 wk postpartum. Cows on all 4 CFM were offered grass silage plus maize silage (in a 70:30 ratio on a DM basis) ad libitum throughout the study. In addition, cows had a target concentrate allocation of 11 kg/cow per day (from d 13 postpartum) via 1 of 4 CFM, consisting of (1) offered on a flat-rate basis via an out-of-parlor feeding system, (2) offered based on individual cow's milk yields in early lactation via an out-of-parlor feeding system, (3) offered as part of a partial mixed ration (target intake of 5 kg/cow per day) with additional concentrate offered based on individual cow's milk yields in early lactation via an out-of parlor feeding system, and (4) offered as part of a partial mixed ration containing a fixed quantity of concentrate for each cow in the group. In addition, all cows were offered 1 kg/cow per day of concentrate pellets via an in parlor feeding system. We detected no effect of CFM on concentrate or total DMI, mean daily milk yield, concentrations and yields of milk fat and protein, or metabolizable energy intakes, requirements, or balances throughout the study. We also found no effects of CFM on mean or final body weight, mean or final body condition score, conception rates to first service, or any of the blood metabolites examined. The results of this study suggest that CFM has little effect on the overall performance of higher-yielding dairy cows in early to mid lactation when offered diets based on conserved forages. PMID- 26805999 TI - Short communication: Ovine leukocyte telomere length is associated with variation in the cortisol response to systemic bacterial endotoxin challenge. AB - Stress has been associated with biological aging and numerous age-related diseases. This may be due, in part, to accelerated shortening of telomeres, which are critical genomic structures that cap and protect chromosomal ends. Dysfunction of the hypothalamic-pituitary-adrenal axis may indirectly contribute to telomere shortening if an animal reacts too strongly or weakly to a stressor, leading to accelerated biological aging. In this study, outbred Rideau-Arcott sheep were stress challenged with Escherichia coli endotoxin and classified as high, middle, or low cortisol responders to investigate a potential relationship between cortisol response and age, and telomere length. In the present study, no association was found between age and telomere length. The study, however, revealed shorter telomeres in high and low cortisol responders compared with the middle cortisol responders, which suggests that health and longevity may be compromised in extreme high- and low-stress-responding sheep. PMID- 26806000 TI - Treponema denticola invasion into human gingival epithelial cells. AB - Host cell invasion is important for periodontal pathogens in evading host defenses and spreading into deeper areas of the periodontal tissue. Treponema denticola has been implicated in a number of potentially pathogenic processes, including periodontal tissue penetration. Here we tested the ability of T. denticola strains to invade human gingival epithelial cells (HGEC). After 2 h infection, intracellular location of T. denticola cells was confirmed by confocal laser scanning microscopy (CLSM). Results from an antibiotic protection assay following [(3)H]uridine labeling indicated that invasion efficiency reached a maximum at 2 h after infection. Internalized T. denticola cells were still observed in HGEC at 24 h by CLSM. A dentilisin deficient mutant exhibited significantly decreased invasion (p < 0.05) compared with the wild-type strain. In inhibition assays, phenylmethylsulfonyl fluoride and metabolic inhibitors such as methyl-beta-cyclodextrin and staurosporine significantly reduced T. denticola invasion. Under CLSM, T. denticola colocalized with GM-1 ganglioside-containing membrane microdomains in a cholesterol-dependent manner. These results indicated that T. denticola has the ability to invade into and survive within HGECs. Dentilisin activity of T. denticola and lipid rafts on HGEC appear to play important roles in this process. PMID- 26806002 TI - Patiromer for Hyperkalemia in Diabetic CKD: A New Kid on the Block. PMID- 26806003 TI - Nephrologist-Facilitated Advance Care Planning for Hemodialysis Patients: A Quality Improvement Project. AB - BACKGROUND: The Renal Physicians Association's clinical practice guideline recommends that physicians address advance care planning with dialysis patients. However, data are lacking about how best to implement this recommendation. STUDY DESIGN: Quality improvement project. SETTINGS & PARTICIPANTS: Nephrologists caring for patients treated with maintenance hemodialysis at 2 dialysis facilities identified patients who might benefit most from advance care planning using the "surprise" question ("Would I be surprised if this patient died in the next year?"). QUALITY IMPROVEMENT PLAN: Patients identified with a "no" response to the surprise question were invited to participate in nephrologist-facilitated advance care planning, including completion of a Medical Orders for Life Sustaining Treatment (MOLST) form. OUTCOMES: Change in MOLST completion rate and identification of preferences for limits on life-sustaining treatment. MEASUREMENTS: Pre- and postintervention code status, MOLST completion rate, and vital status at 1 year. RESULTS: Nephrologists answered "no" to the surprise question for 50 of 201 (25%) hemodialysis patients. Of these, 41 (82%) patients had a full-code status and 9 (18%) had a do-not-resuscitate (DNR) status. Encounters lasted 15 to 60 minutes. Following the encounter, 21 (42%) patients expressed preference for a DNR status and 29 (58%) maintained full-code status (P=0.001). The MOLST completion rate increased from 10% to 90%. One-year survival for patients whose nephrologists answered "no" to the surprise question was 58% compared to 92% for those with a "yes" answer (P<0.001). LIMITATIONS: Sample size and possible nonrepresentative dialysis population. CONCLUSIONS: Nephrologist facilitated advance care planning targeting hemodialysis patients with limited life expectancy led to significant changes in documented patient preferences for cardiopulmonary resuscitation and limits on life-sustaining treatment. These changes demonstrate the benefit of advance care planning with dialysis patients and likely reflect better understanding of end-of-life treatment options. PMID- 26806004 TI - Advances in Urine Microscopy. AB - Urine microscopy is an important tool for the diagnosis and management of several conditions affecting the kidneys and urinary tract. In this review, we describe the automated instruments, based either on flow cytometry or digitized microscopy, that are currently in use in large clinical laboratories. These tools allow the examination of large numbers of samples in short periods. We also discuss manual urinary microscopy commonly performed by nephrologists, which we encourage. After discussing the advantages of phase contrast microscopy over bright field microscopy, we describe the advancements of urine microscopy in various clinical conditions. These include persistent isolated microscopic hematuria (which can be classified as glomerular or nonglomerular on the basis of urinary erythrocyte morphology), drug- and toxin-related cystalluria (which can be a clue for the diagnosis of acute kidney injury associated with intrarenal crystal precipitation), and some inherited conditions (eg, adenine phosphoribosyltransferase deficiency, which is associated with 2,8 dihydroxyadenine crystalluria, and Fabry disease, which is characterized by unique urinary lamellated fatty particles). Finally, we describe the utility of identifying "decoy cells" and atypical malignant cells, which can be easily done with phase contrast microscopy in unfixed samples. PMID- 26806006 TI - Multicomponent reactions of phosphines, enynedioates and benzylidene malononitriles generated highly substituted cyclopentenes through an unexpected phosphine alpha-addition-delta-evolvement of an anion pathway. AB - Multicomponent reactions of phosphines, enynedioates and benzylidene malononitriles provide highly substituted syn-selective cyclopentenes appending the phosphorus ylide moiety in good yield with a diastereoselectivity of up to 100% through resonance-derived 1,5-dipolar species as the key intermediates, via the nucleophilic alpha(delta')-attack of phosphines toward enynedioates followed by addition to benzylidene malononitriles and 5-exo-dig cyclization. Through computational analyses, the overall reactions for the formation of syn- and anti diastereomers are both exothermic with 65.6 and 66.3 kcal mol(-1) at the B3LYP D3/6-31G(d) level of theory and were found to be kinetically controlled, which favours the formation of syn-diastereomers. PMID- 26806005 TI - Monitoring an epidemic of Theileria-associated bovine anaemia (Ikeda) in cattle herds in New Zealand. AB - Monitoring an epidemic of an emerging vector-borne disease can be problematic; particularly in a country where vector-borne disease has previously had minimal impact on livestock. This paper describes methods of past and current surveillance of the Theileria-associated bovine anaemia (Ikeda; TABA) epidemic in New Zealand, and the resulting inferences made. Over the three year period of the TABA epidemic a portfolio of surveillance methods has been used: case reporting (with subsidised PCR testing), syndromic surveillance, sentinel surveillance, testing convenience samples for herd infection, as well as specific active surveillance initiatives to understand the tick vector distribution. Surveillance data have shown that the number of affected cattle herds has continued to increase over time with seasonal peaks in spring and autumn coinciding with peak activity of nymph and adult ticks respectively. In spring 2014, the epidemic extended south into areas that were previously considered to be unsuitable for the tick vector. As a result a survey was initiated that showed that ticks were present in areas outside of the known distribution. Testing pooled blood samples from cattle herds across New Zealand showed there still remained a significant percentage of herds where only non-Ikeda type infections were present, indicating that these herds were at risk of future TABA (Ikeda) outbreaks. For some regions there had been a noticeable increase in the percentage of herds infected, yet with only a small increase in the number of outbreaks compared with the previous year. Thus, outbreaks had either gone unobserved or had not been confirmed by testing. In these regions extensive low-input beef farming could explain the non detection observed. There was a close relationship between the number of syndromic reports of anaemia and the number of confirmed cases of TABA (Ikeda), (P<0.01, adjusted R-squared=0.74). Active monitoring of the epidemic for a three year period has provided valuable insight into seasonal nature of the disease and its continuing impact. Information from multiple surveillance sources can help build up an understanding of the epidemiology, even when data from each individual surveillance stream are limited. The TABA (Ikeda) epidemic in New Zealand represents a useful case study of long term monitoring where disease is caused by an emerging pathogen. PMID- 26806007 TI - Automatic and objective oral cancer diagnosis by Raman spectroscopic detection of keratin with multivariate curve resolution analysis. AB - We have developed an automatic and objective method for detecting human oral squamous cell carcinoma (OSCC) tissues with Raman microspectroscopy. We measure 196 independent Raman spectra from 196 different points of one oral tissue sample and globally analyze these spectra using a Multivariate Curve Resolution (MCR) analysis. Discrimination of OSCC tissues is automatically and objectively made by spectral matching comparison of the MCR decomposed Raman spectra and the standard Raman spectrum of keratin, a well-established molecular marker of OSCC. We use a total of 24 tissue samples, 10 OSCC and 10 normal tissues from the same 10 patients, 3 OSCC and 1 normal tissues from different patients. Following the newly developed protocol presented here, we have been able to detect OSCC tissues with 77 to 92% sensitivity (depending on how to define positivity) and 100% specificity. The present approach lends itself to a reliable clinical diagnosis of OSCC substantiated by the "molecular fingerprint" of keratin. PMID- 26806011 TI - Creating Change. PMID- 26806010 TI - A time and motion study of subcutaneous versus intravenous trastuzumab in patients with HER2-positive early breast cancer. AB - Within PrefHer (NCT01401166), patients and healthcare professionals (HCPs) preferred subcutaneous (SC) over intravenous (IV) trastuzumab. We undertook a prospective, observational time and motion study to quantify patients' time in infusion chairs and active HCP time in PrefHer. Patients with HER2-positive early breast cancer received four adjuvant cycles of SC trastuzumab (600 mg fixed dose via SC single-use injection device [SID, Cohort 1] or SC handheld syringe [HHS, Cohort 2]) then four cycles of standard IV trastuzumab or the reverse sequence. Generic case report forms for IV and SC management, both in the treatment room and the drug preparation area, were tailored to reflect center practices. Patient chair time and active HCP time were recorded. We compared pooled Cohort 1 + 2 IV with Cohort 1 SC SID and Cohort 2 SC HHS mean times across eight countries and individually within them utilizing a random intercept generalized linear mixed effects model. Per session, the SC SID saved a mean of 57 min of patient chair time versus IV (range across countries: 47-86; P < 0.0001); the SC HHS saved 55 min (40-81; P < 0.0001). Active HCP time was reduced by a mean of 13 min per session with the SC SID (range across countries: 4-16; P < 0.0001) and 17 min with the SC HHS (5-28; P < 0.0001) versus IV. SC trastuzumab, delivered via SID or HHS, saved patient chair and active HCP times versus IV infusion, supporting a transition to either SC method. PMID- 26806013 TI - Abnormal brain activation and connectivity to standardized disorder-related visual scenes in social anxiety disorder. AB - Our understanding of altered emotional processing in social anxiety disorder (SAD) is hampered by a heterogeneity of findings, which is probably due to the vastly different methods and materials used so far. This is why the present functional magnetic resonance imaging (fMRI) study investigated immediate disorder-related threat processing in 30 SAD patients and 30 healthy controls (HC) with a novel, standardized set of highly ecologically valid, disorder related complex visual scenes. SAD patients rated disorder-related as compared with neutral scenes as more unpleasant, arousing and anxiety-inducing than HC. On the neural level, disorder-related as compared with neutral scenes evoked differential responses in SAD patients in a widespread emotion processing network including (para-)limbic structures (e.g. amygdala, insula, thalamus, globus pallidus) and cortical regions (e.g. dorsomedial prefrontal cortex (dmPFC), posterior cingulate cortex (PCC), and precuneus). Functional connectivity analysis yielded an altered interplay between PCC/precuneus and paralimbic (insula) as well as cortical regions (dmPFC, precuneus) in SAD patients, which emphasizes a central role for PCC/precuneus in disorder-related scene processing. Hyperconnectivity of globus pallidus with amygdala, anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) additionally underlines the relevance of this region in socially anxious threat processing. Our findings stress the importance of specific disorder-related stimuli for the investigation of altered emotion processing in SAD. Disorder-related threat processing in SAD reveals anomalies at multiple stages of emotion processing which may be linked to increased anxiety and to dysfunctionally elevated levels of self-referential processing reported in previous studies. PMID- 26806014 TI - The impact of robotic cholecystectomy on private practice in a community teaching hospital. AB - BACKGROUND: Recently, through aggressive marketing, robotic cholecystectomy has been gaining popularity. The purpose of this study was to evaluate the impact of this technology on private practice and hospital cost and volume. METHODS: From November 2012 to April 2014, all elective cholecystectomies were evaluated for procedure type, operative time (OR), insurance type and payment, hospital length of stay, and volume. Data were analyzed using the Chi-square test, Student t test and the Mann-Whitney U test. RESULTS: Of 338 patients, 246 had complete financial records. Of these patients, 84.1% (207) patients were female with mean age of 45.4 +/- 17.1 years. Patients were divided into 2 groups; group 1: 220(89.4%) patients had laparoscopic cholecystectomy (LC) and group 2: 26(10.6%) patients had robotic cholecystectomy (RC). The mean direct cost was higher in the robotic group $2,704.08 +/- 308.40 vs $1,712.51 +/- 379.50; P < .0001. The median gross margin; however, was not statically different (RC: $1,593.00 (Interquartile range $3,936) vs LC: $1,726.00 (Interquartile range $1,480); P = .85). Both case time and OR were higher in the robotic group; case time (RC: 121 +/- 15.4 vs LC: 98.4 +/- 27.5 minutes, P < .0001); OR (RC: 86.6 +/- 14.3 vs LC: 63.9 +/- 25.9 minutes, P < .0001). There was no appreciable change over time in either surgeon or hospital volume. CONCLUSIONS: There was a statistically significant increase in direct cost in RC vs. LC but not in margin. There was no impact in private practice on the number of cases being done robotically, nor there was an increase in hospital volume. This analysis did not include the purchase cost or maintenance of the robot. PMID- 26806016 TI - A practical cobalt-catalyzed cross-coupling of benzylic zinc reagents with aryl and heteroaryl bromides or chlorides. AB - A catalytic system consisting of 5 mol% CoCl2 and 10 mol% isoquinoline allows a convenient cross-coupling of benzylic zinc reagents with various aryl and heteroaryl bromides or chlorides leading to polyfunctionalized diaryl- and aryl heteroaryl-methane derivatives. PMID- 26806017 TI - What is an optimal sequential OSCE model? PMID- 26806015 TI - Functional annotation of rare gene aberration drivers of pancreatic cancer. AB - As we enter the era of precision medicine, characterization of cancer genomes will directly influence therapeutic decisions in the clinic. Here we describe a platform enabling functionalization of rare gene mutations through their high throughput construction, molecular barcoding and delivery to cancer models for in vivo tumour driver screens. We apply these technologies to identify oncogenic drivers of pancreatic ductal adenocarcinoma (PDAC). This approach reveals oncogenic activity for rare gene aberrations in genes including NAD Kinase (NADK), which regulates NADP(H) homeostasis and cellular redox state. We further validate mutant NADK, whose expression provides gain-of-function enzymatic activity leading to a reduction in cellular reactive oxygen species and tumorigenesis, and show that depletion of wild-type NADK in PDAC cell lines attenuates cancer cell growth in vitro and in vivo. These data indicate that annotating rare aberrations can reveal important cancer signalling pathways representing additional therapeutic targets. PMID- 26806018 TI - Physical exercise training for cystic fibrosis. PMID- 26806020 TI - Multilayer Nanoporous Graphene Membranes for Water Desalination. AB - While single-layer nanoporous graphene (NPG) has shown promise as a reverse osmosis (RO) desalination membrane, multilayer graphene membranes can be synthesized more economically than the single-layer material. In this work, we build upon the knowledge gained to date toward single-layer graphene to explore how multilayer NPG might serve as a RO membrane in water desalination using classical molecular dynamic simulations. We show that, while multilayer NPG exhibits similarly promising desalination properties to single-layer membranes, their separation performance can be designed by manipulating various configurational variables in the multilayer case. This work establishes an atomic level understanding of the effects of additional NPG layers, layer separation, and pore alignment on desalination performance, providing useful guidelines for the design of multilayer NPG membranes. PMID- 26806022 TI - Life histories of two deep-water Australian endemic elasmobranchs: Argus skate Dipturus polyommata and eastern spotted gummy shark Mustelus walkeri. AB - Two Australian endemic elasmobranchs, the Argus skate Dipturus polyommata and the eastern spotted gummy shark Mustelus walkeri, were collected from the by-catch of a prawn Melicertus plebejus trawl fishery off Queensland. Age and growth parameters were estimated from growth band counts in vertebral sections of 220 D. polyommata and 44 M. walkeri. Dipturus polyommata males and females had an observed maximum age of 10 years and reached maximum sizes of 369 and 371 mm total length (LT ), respectively. Mustelus walkeri lived longer, with the oldest female aged 16 years and measuring 1050 mm stretched total length (LST ), and oldest male aged 9 years and 805 mm LST . Dipturus polyommata grew relatively fast with a von Bertalanffy growth completion parameter of k = 0.208 year(-1) with males reaching maturity at 4.0 years (c. 278 mm LT ) and females at 5.1 years (c. 305 mm LT ). Mustelus walkeri grew more slowly with k = 0.033 year(-1) with males estimated to mature at 7-9 years (670-805 mm LST ) and females at 10 14 years (833-1012 mm LST ). Length at birth inferred from neonate D. polyommata was 89-111 mm LT while for M. walkeri it was estimated to be 273 LST based on the value of L0 from the von Bertalanffy growth model. Both species appeared to have continuous reproductive cycles and low fecundity with an average ovarian fecundity of eight follicles for D. polyommata and a litter size of five to seven pups for M. walkeri. Based on these life-history traits, D. polyommata is more resilient to fishing pressure than M. walkeri. PMID- 26806019 TI - Tectorins crosslink type II collagen fibrils and connect the tectorial membrane to the spiral limbus. AB - All inner ear organs possess extracellular matrix appendices over the sensory epithelia that are crucial for their proper function. The tectorial membrane (TM) is a gelatinous acellular membrane located above the hearing sensory epithelium and is composed mostly of type II collagen, and alpha and beta tectorins. TM molecules self-assemble in the endolymph fluid environment, interacting medially with the spiral limbus and distally with the outer hair cell stereocilia. Here, we used immunogold labeling in freeze-substituted mouse cochleae to assess the fine localization of both tectorins in distinct TM regions. We observed that the TM adheres to the spiral limbus through a dense thin matrix enriched in alpha- and beta-tectorin, both likely bound to the membranes of interdental cells. Freeze-etching images revealed that type II collagen fibrils were crosslinked by short thin filaments (4+/-1.5nm, width), resembling another collagen type protein, or chains of globular elements (15+/-3.2nm, diameter). Gold-particles for both tectorins also localized adjacent to the type II collagen fibrils, suggesting that these globules might be composed essentially of alpha- and beta tectorins. Finally, the presence of gold-particles at the TM lower side suggests that the outer hair cell stereocilia membrane has a molecular partner to tectorins, probably stereocilin, allowing the physical connection between the TM and the organ of Corti. PMID- 26806023 TI - Radiosynthesis of the iodine-124 labeled Hsp90 inhibitor PU-H71. AB - Heat shock protein 90 (Hsp90) is an ATP dependent molecular chaperone protein whose function is critical for maintaining several key proteins involved in survival and proliferation of cancer cells. PU-H71 (1), is a potent purine scaffold based ATP pocket binding Hsp90 inhibitor which has been shown to have potent activity in a broad range of in vivo cancer models and is currently in Phase I clinical trials in patients with advanced solid malignancies, lymphomas, and myeloproliferative neoplasms. In this report, we describe the radiosynthesis of [(124)I]-PU-H71(5); this was synthesized from the corresponding Boc-protected stannane precursor 3 by iododestannylation with [(124)I]-NaI using chloramine-T as an oxidant for 2 min, followed by Boc deprotection with 6 N HCl at 50 degrees C for 30 min to yield the final compound. The final product 5 was purified using HPLC and was isolated with an overall yield of 55 +/- 6% (n = 6, isolated) from 3, and >98% purity and an average specific activity of 980 mCi/umol. Our report sets the stage for the introduction of [(124)I]-PU-H71 as a potential non invasive probe for understanding biodistribution and pharmacokinetics of PU-H71 in living subjects using positron emission tomography imaging. PMID- 26806024 TI - Age-related macular degeneration in Portugal: prevalence and risk factors in a coastal and an inland town. The Coimbra Eye Study - Report 2. AB - PURPOSE: To determine the age- and sex-specific prevalence of early and late age related macular degeneration (AMD) in two Portuguese population-based samples and to identify its risk factors. POPULATION: A population of 6023 adults aged >=55 years was recruited from two Portuguese primary healthcare units in the central region of Portugal - one from a coastal (n = 3000) and another from an inland town (n = 3023). METHODS: Cross-sectional population-based study. Participants were enrolled in the two locations between August 2009 and October 2013. Responders underwent standardized interviews and ophthalmologic examination, including digital fundus imaging. All fundus photographs were graded according to an International Classification and Grading System. The main outcome measures consisted of age- and sex-adjusted prevalence of early and late AMD. Potential epidemiologic risk factors were also evaluated using logistic regression analysis. RESULTS: Of the 6023 subjects enrolled, 5996 had gradable fundus images and were included in the analysis. The crude prevalence of early and late AMD was 6.99 and 0.67%, respectively, for the coastal town and 15.39 and 1.29% for the inland town. Age- and sex-adjusted prevalence of any AMD for the Portuguese population was 12.48% (95% CI: 11.61-13.33) with late AMD accounting for 1.16% (95% CI: 0.85-1.46). Neovascular AMD (NV-AMD) and geographic atrophy (GA) accounted for 0.55% (95% CI: 0.36-0.75) and 0.61% (95% CI: 0.37-0.84) of individuals, respectively. After adjusting for possible confounding factors, prevalence of early and late AMD increased with increasing age (OR = 1.35; 95% CI: 1.23-1.49 for early and OR = 3.01; 95% CI: 2.22-4.08 for late AMD, per each decade of age increase, p < 0.001). After adjustment for age, sex, family history, smoking history, hypertension, diabetes and BMI, subjects from the inland town presented a significantly higher OR of early and late AMD than subjects from the coastal town (OR = 2.57, 95% CI: 2.12-3.12, p < 0.001 for early and OR = 2.06, 95% CI: 1.07-3.95, p = 0.029 for late AMD). CONCLUSIONS: The prevalence of early and late AMD in this Portuguese population was similar to other large-scale population-based cohorts. After controlling for confounders, age and study site of inclusion were significant independent predictors for both early and late forms of the disease. Further analysis will be needed to completely unravel the underlying reasons for this difference regarding geographic location. PMID- 26806025 TI - Safety of heat generated by endoscope light sources in simulated transcanal endoscopic ear surgery. AB - OBJECTIVE: To determine whether heat generated by endoscope light sources during ear surgery is safe. METHODS: Transcanal endoscopic ear surgery (TEES) was simulated using 2.7-mm or 4-mm endoscopes coupled to xenon or LED light sources and a 3D model of human temporal bone. The endoscope tip was fixed at the center of tympanic annulus. Light sources were tested at clinical (30% for xenon and 40% for LED) and 100% settings. Temperatures were measured using thermocouples attached to the endoscope tip and three points within the middle ear cavity: promontory, horizontal portion of the facial nerve and lateral semicircular canal. RESULTS: Maximum temperatures measured within the middle ear cavity were below 31 degrees C at clinical settings, while the temperatures rose to 44.1 degrees C using a 4-mm endoscope with a xenon light source set at 100%. Temperatures measured at the tip were all safe at clinical settings, but rose dramatically to 110.1 degrees C for the 4-mm endoscope with xenon at 100%. CONCLUSION: Endoscopes can be safely used within the middle ear at clinical settings. However, operators should not exceed clinical settings, particularly with 4-mm endoscopes with a xenon light source, to ensure temperatures generated within the middle ear cavity are safe. PMID- 26806026 TI - Not appropriate dinner table conversation? Talking to children about meat production. AB - Although Australians on average consume large quantities of meat, their attitudes to farm animal welfare are poorly understood. We know little about how farm animal production is discussed in Australian households or how children learn about the origins of meat. This study consisted of an online survey completed by 225 primary carers throughout Australia recruited through social media. Findings include that conversations about the origin of meat were generally stimulated by meal preparation within the home rather than visits to agricultural shows or similar activities. Parents preferred to initiate conversations with children about meat production before they were 5 years of age. Urban parents were more likely than rural parents to reveal that they were conflicted about eating meat and would be more empathetic to children who chose to stop eating meat. Rural parents were more likely than urban parents to feel that children should eat what they are given and that talking about meat is not a major issue. Both groups felt that it was important that children should know where their food comes from. The findings of this study suggest that parental attitudes to meat production and consumption influence conversations about meat origins with children. PMID- 26806028 TI - Transthyretin-related hereditary amyloid polyneuropathy presenting with large fibre involvement and cardiomyopathy. PMID- 26806029 TI - Site-Specific Difunctionalization of Structured RNAs Yields Probes for microRNA Maturation. AB - Modified oligonucleotides bearing multiple functional labels are valuable tools in RNA biology. Efficient synthetic access to singly modified short DNAs and RNAs has been developed in the past years and paved the way to a first generation of oligonucleotide tools. Here, we describe an efficient procedure for the site specific hetero bis-labeling of long RNAs. We exemplified the method with the preparation of Cy3/Cy5 pre-microRNAs labeled at selected internal sites as probes for microRNA maturation. PMID- 26806030 TI - Comparing the quality of life of adults with and without intellectual disability. AB - BACKGROUND: Quality of life (QOL) is an important issue for all citizens, comprising equity, equality, inclusion and participation of each person in society. The research purposes driving this investigation were (1) to compare QOL among people with and without intellectual disability (ID) and (2) to examine the predictors of QOL in both groups of participants. METHODS: Data were collected from 1929 adults, including 1264 individuals with an ID and the remainder (n = 665) were participants without a disability. QOL was assessed by the Portuguese version of the Personal Outcomes Scale. RESULTS: The findings supported significantly higher QOL for adults without ID. Furthermore, QOL is influenced by individual and environmental variables, stressing that the health status was the highest mutual predictor of QOL among those with and without ID. CONCLUSION: The gaps among both groups of participants should be addressed in service provision and policies. Taking into account the research findings, the personalised supports should enable the full inclusion and participation of adults with ID in community-based settings. PMID- 26806033 TI - Structural and functional characterization of phosphomimetic mutants of cytochrome c at threonine 28 and serine 47. AB - Protein function is frequently modulated by post-translational modifications of specific residues. Cytochrome c, in particular, is phosphorylated in vivo at threonine 28 and serine 47. However, the effect of such modifications on the physiological functions of cytochrome c - namely, the transfer of electrons in the respiratory electron transport chain and the triggering of programmed cell death - is still unknown. Here we replace each of these two residues by aspartate, in order to mimic phosphorylation, and report the structural and functional changes in the resulting cytochrome c variants. We find that the T28D mutant causes a 30-mV decrease on the midpoint redox potential and lowers the affinity for the distal site of Arabidopsis thaliana cytochrome c1 in complex III. Both the T28D and S47D variants display a higher efficiency as electron donors for the cytochrome c oxidase activity of complex IV. In both protein mutants, the peroxidase activity is significantly higher, which is related to the ability of cytochrome c to leave the mitochondria and reach the cytoplasm. We also find that both mutations at serine 47 (S47D and S47A) impair the ability of cytoplasmic cytochrome c to activate the caspases cascade, which is essential for triggering programmed cell death. PMID- 26806032 TI - Bladder ultrasonography for diagnosing detrusor overactivity: test accuracy study and economic evaluation. AB - BACKGROUND: Urodynamics (UDS) has been considered the gold standard test for detrusor overactivity (DO) in women with an overactive bladder (OAB). Bladder ultrasonography to measure bladder wall thickness (BWT) is less invasive and has been proposed as an alternative test. OBJECTIVES: To estimate the reliability, reproducibility, accuracy and acceptability of BWT in women with OAB, measured by ultrasonography, in the diagnosis of DO; to explore the role of UDS and its impact on treatment outcomes; and to conduct an economic evaluation of alternative care pathways. DESIGN: A cross-sectional test accuracy study. SETTING: 22 UK hospitals. PARTICIPANTS: 687 women with OAB. METHODS: BWT was measured using transvaginal ultrasonography, and DO was assessed using UDS, which was performed blind to ultrasonographic findings. Intraobserver and interobserver reproducibility were assessed by repeated measurements from scans in 37 and 57 women, respectively, and by repeated scans in 27 women. Sensitivity and specificity were computed at pre-specified thresholds. The smallest real differences detectable of BWT were estimated using one-way analysis of variance. The pain and acceptability of both tests were evaluated by a questionnaire. Patient symptoms were measured before testing and after 6 and 12 months using the International Consultation on Incontinence modular Questionnaire Overactive Bladder (short form) (ICIQ-OAB) questionnaire and a global impression of improvement elicited at 12 months. Interventions and patient outcomes were analysed according to urodynamic diagnoses and BWT measurements. A decision analytic model compared the cost-effectiveness of care strategies using UDS, ultrasonography or clinical history, estimating the cost per woman successfully treated and the cost per quality-adjusted life-year (QALY). RESULTS: BWT showed very low sensitivity and specificity at all pre-specified cut-off points, and there was no evidence of discrimination at any threshold (p = 0.25). Extensive sensitivity and subgroup analyses did not alter the interpretation of these findings. The smallest detectable difference in BWT was estimated to be 2 mm. Pain levels following both tests appeared relatively low. The proportion of women who found the test 'totally acceptable' was significantly higher with ultrasonography than UDS (81% vs. 56%; p < 0.001). Overall, subsequent treatment was highly associated with urodynamic diagnosis (p < 0.0001). There was no evidence that BWT had any relationship with the global impression of improvement responses at 20 months (p = 0.4). Bladder ultrasonography was more costly and less effective than the other strategies. The incremental cost-effectiveness ratio (ICER) of basing treatment on the primary clinical presentation compared with UDS was L491,500 per woman successfully treated and L60,200 per QALY. Performing a UDS in those women with a clinical history of mixed urinary incontinence had an ICER of L19,500 per woman successfully treated and L12,700 per QALY compared with the provision of urodynamic to all women. For DO cases detected, UDS was the most cost-effective strategy. CONCLUSION: There was no evidence that BWT had any relationship with DO, regardless of the cut-off point, nor any relationship to symptoms as measured by the ICIQ-OAB. Bladder ultrasonography has no diagnostic or prognostic value as a test in this condition. Furthermore, despite its greater acceptability, BWT measurement was not sufficiently reliable or reproducible. TRIAL REGISTRATION: Current Controlled Trials ISRCTN46820623. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 7. See the NIHR Journals Library website for further project information. PMID- 26806034 TI - Investigation of faecal volatile organic metabolites as novel diagnostic biomarkers in inflammatory bowel disease. AB - BACKGROUND: The aetiology of inflammatory bowel disease (IBD) remains poorly understood. Recent evidence suggests an important role of gut microbial dysbiosis in IBD, and this may be associated with changes in faecal volatile organic metabolites (VOMs). AIM: To describe the changes in the faecal VOMs of patients with IBD and establish their diagnostic potential as non-invasive biomarkers. METHODS: Faecal samples were obtained from 117 people with Crohn's disease (CD), 100 with ulcerative colitis (UC), and 109 healthy controls. Faecal VOMs were extracted using solid-phase micro-extraction and analysed by gas chromatography mass spectrometry. Data analysis was carried out using partial least squares discriminate analysis (PLS-DA) to determine class membership based on distinct metabolomic profiles. RESULTS: The PLS-DA model showed clear separation of active CD from inactive disease and healthy controls (P < 0.001). Heptanal, 1-octen-3 ol, 2-piperidinone and 6-methyl-2-heptanone were up-regulated in the active CD group [variable important in projection (VIP) score 2.8, 2.7, 2.6 and 2.4, respectively], while methanethiol, 3-methyl-phenol, short-chain fatty acids and ester derivatives were found to be less abundant (VIP score of 3.5, 2.6, 1.5 and 1.2, respectively). The PLS-DA model also separated patients with small bowel CD from healthy controls and those with colonic CD from UC (P < 0.001). In contrast, less distinct separation was observed between active UC, inactive UC and healthy controls. CONCLUSIONS: Analysis of faecal volatile organic metabolites can provide an understanding of gut metabolomic changes in IBD. It has the potential to provide a non-invasive means of diagnosing IBD, and can differentiate between UC and CD. PMID- 26806035 TI - Novel environment influences the effect of paradoxical sleep deprivation upon brain and peripheral cytokine gene expression. AB - Sleep loss increases inflammatory mediators in brain and peripheral tissues, but the mechanisms underlying this association are not fully understood. Male C57BL/6j mice were exposed to paradoxical sleep deprivation (PSD) for 24h using the modified multiple platform (MMP) technique (platforms over water) or two different controls: home cage or a dry platform cage, which constituted a novel environment. PSD mice exhibited increased IL-1beta and TNF-alpha pro-inflammatory gene expression in brain (hypothalamus, hippocampus, pre-frontal cortex), as well as in peripheral tissues (liver, spleen), when compared with home-cage controls. In addition, among PSD mice, TGFbeta1, an anti-inflammatory cytokine, was increased in pre-frontal cortex, liver, and spleen in conjunction with elevated serum corticosterone concentration relative to home-cage controls. However, these differences were nearly abolished when PSD mice were compared with control mice subjected to a dry MMP cage, suggesting that simply exposing mice to a novel environment can induce an acute inflammatory response. PMID- 26806037 TI - Influence of repetitive transcranial magnetic stimulation on tibialis anterior activity during walking in humans. AB - OBJECTIVE: To determine whether or not modulation of the excitability of the M1 region controlling the lower limb (using repetitive transcranial magnetic stimulation; TMS) would change the TA's activity during gait and the effect of aging on this change. METHODS: In three separate sessions, participants underwent different repetitive TMS (rTMS) protocols (sham stimulation, intermittent theta burst stimulation (TBS) and continuous TBS) delivered over the M1 region controlling the lower limb muscles, using a focal, figure-of-eight coil. Before and after rTMS, the TA's activity was recorded using surface electrodes while participants walked at a freely chosen speed and at an imposed speed on a treadmill. Cortical excitability was assessed by characterizing input-output (IO) curves, after fitting the relationship between motor evoked potential amplitude and stimulus intensity with a Boltzmann sigmoidal equation. RESULTS: We did not observe any effects of rTMS in terms of TA activation during locomotion, gait parameters or IO curves in either healthy young adults or elderly adults. Elderly patients presented lower excitability of cortical TA representation area. CONCLUSION: Modulation of TA activity by TBS was ineffective contrary to what is observed for upper limbs. Interindividual variability in the effects of rTMS on TA activation, activation of the TA before the rTMS and/or differences in the depth of the cortical representation of the TA could have influenced the results and should be taken into account for further studies. PMID- 26806036 TI - Effect of spinal monoaminergic neuronal system dysfunction on pain threshold in rats, and the analgesic effect of serotonin and norepinephrine reuptake inhibitors. AB - Dysfunction in the central serotonin (5-HT) and norepinephrine (NE) systems cause depression and pain. Descending spinal pain modulatory pathways are important in the analgesic mechanisms of antidepressants, particularly serotonin and norepinephrine reuptake inhibitors (SNRIs). While many non-clinical studies have demonstrated the roles of central monoaminergic systems in pain, there is little evidence to illuminate the direct contribution of spinal descending pain modulatory systems independently of depressive-like behavior. To examine the effects of dysfunction of spinal monoaminergic systems on pain sensitivity, we established a rat chronic pain model by administering lumbar-intrathecal reserpine to minimize its influence on brain. Lumbar-intrathecal reserpine evoked persistent mechanical hypersensitivity and corresponding reductions in spinal 5 HT and NE concentrations (from 767.2 to 241.6ng/g and from 455.9 to 41.7ng/g, respectively after reserpine 30nmol). Lumbar-intrathecal reserpine did not deplete brain monoamines or bring about depressive-like behavior in the forced swim test. Spinal monoamines depletion-induced pain sensitivity was ameliorated by lumbar-intrathecal administration of the SNRIs (duloxetine and milnacipran) in dose-dependent manners. These suggest that increased pain sensitivity could be induced by dysfunction solely of the descending pain modulatory system, regardless of depressive-like behavior, and lumbar-intrathecal administration of SNRIs could ameliorate the pain sensitivity which might be mediated by affecting the descending pain modulatory system in the spinal cord, not via their antidepressant effects. PMID- 26806038 TI - The role of active DNA demethylation and Tet enzyme function in memory formation and cocaine action. AB - Active DNA modification is a major epigenetic mechanism that regulates gene expression in an experience-dependent manner, which is thought to establish stable changes in neuronal function and behavior. Recent discoveries regarding the Ten eleven translocation (Tet1-3) family of DNA hydroxylases have provided a new avenue for the study of active DNA demethylation, and may thus help to advance our understanding of how dynamic DNA modifications lead to long-lasting changes in brain regions underlying learning and memory, as well as drug-seeking and propensity for relapse following abstinence. Drug addiction is a complex, relapsing disorder in which compulsive drug-seeking behavior can persist despite aversive consequences. Therefore, understanding the molecular mechanisms that underlie the onset and persistence of drug addiction, as well as the pronounced propensity for relapse observed in addicts, is necessary for the development of selective treatments and therapies. In this mini-review, we provide an overview of the involvement of active DNA demethylation with an emphasis on the Tet family of enzymes and 5-hydroxymethylcytosine (5-hmC) in learning and memory, as well as in drug-seeking behavior. Memory and addiction share overlapping molecular, cellular, and circuit functions allowing research in one area to inform the other. Current discrepancies and directions for future studies focusing on the dynamic interplay between DNA methylation and demethylation, and how they orchestrate gene expression required for neuronal plasticity underlying memory formation, are discussed. PMID- 26806040 TI - Preventive and Therapeutic Effects of the Retinoid X Receptor Agonist Bexarotene on Tumors. AB - We present a review of recent investigations of anticancer drug bexarotene in this article. As one of the novel synthetic analogs of retinoids, bexarotene selectively binds to and activates the retinoid X receptor (RXRs) subfamilies, exerting a prophylactic and therapeutic effect on a large series of tumors in vitro and in vivo covering cutaneous lesions, lung and breast cancers, nervous system diseases etc. Bexarotene has been proved to have a specifically favorable therapeutic profile in clinical dermatology or oncology with mild or absent retinoids side effects, especially in combination with other therapies. It is noteworthy that numerous previous outstanding researches have contributed to the chemical, biological, preclinical and clinical examinations of bexarotene during the past decades, with a relatively deficient progress of bexarotene in the field of pharmacy. In this review, the positive therapeutic results of bexarotene used as a monotherapy or combination therapy both in preclinical and clinical studies are reported based on relevant medical data; the distinct acting mechanisms of bexarotene are described; the potential studies and prospects of bexarotene in pharmaceutical domain are discussed. All the reports above collectively present bexarotene as a promising anti-cancer agent. PMID- 26806039 TI - Nestin-positive/SOX2-negative cells mediate adult neurogenesis of nigral dopaminergic neurons in mice. AB - The primary clinical motor symptoms of Parkinson's disease (PD) result from loss of dopaminergic (DA) neurons in the substantia nigra (SN). Consequently, neurogenesis of this group of neurons in the adult brain has drawn considerable interest for the purpose of harnessing endogenous neurogenerative potential as well as devising better strategies for stem cell therapy for PD. However, the existence of adult neurogenesis for DA neurons within the SN remains controversial. To overcome technical and design limitations associated with previous studies, our group has developed a novel genetic mouse model for assessing adult nigral DA neurogenesis. This system utilizes transgenic mice that express a tamoxifen-activatable Cre recombinase (Cre(ERT2)) under the control of the neuronal progenitor cell promoters nestin or Sox2 leading to suppression of the DA neuron marker tyrosine hydroxylase (TH) via excision of exon 1 by flanking loxP sites in adult animals. This study reports that six months following initiation of a six week treatment with tamoxifen mice with nestin-mediated Th excision displayed a significant reduction in TH+ neurons in the SN. This finding indicates that nestin-expressing cells regenerate DA neurons within the SN of adult animals. Interestingly, no reduction was observed in TH+ cells following Sox2-mediated Th excision suggesting that a nestin+/SOX2- precursor cell population drives DA neurogenesis in the adult SN. This information represents a substantial leap in current knowledge of adult DA neurogenesis, will enable improved in vitro and in vivo modeling, as well as facilitate the harnessing of this process for therapeutic intervention for PD. PMID- 26806041 TI - Neuroprotective Role of Nanoparticles Against Alzheimer's Disease. AB - BACKGROUND: Alzheimer's disease (AD) is a devastative neurodegenerative disorder with a complex etiology. Despite numerous novel nanotechnology methods targeted against cancer and neurodegenerative diseases such as AD in the past decade, several challenges impeded their success. OBJECTIVE: We ventured to circumvent these challenges by synthesizing redox nanoparticles (RNP) such as Nitroxide radical, 2,2,6,6 tetramethylpiperidinyl-N-oxyl (TEMPO). Piperine in association with RNP successfully scavenges reactive oxygen species (ROS). Our studies have also shown that the piperine associated with RNP confers enhanced protection against AD in vitro. CONCLUSION: This review summarizes our recent findings on the protective roles of redox nanoparticles both in vitro and in vivo. In addition, vital role of nanoparticles employed to encapsulate natural compounds such as curcumin and metal chelators has been summarized. We warrant further studies in animal models using these protective nanoparticles. PMID- 26806044 TI - Mitochondrial drug targets in neurodegenerative diseases. AB - Growing evidence suggests that mitochondrial dysfunction is the main culprit in neurodegenerative diseases. Given the fact that mitochondria participate in diverse cellular processes, including energetics, metabolism, and death, the consequences of mitochondrial dysfunction in neuronal cells are inevitable. In fact, new strategies targeting mitochondrial dysfunction are emerging as potential alternatives to current treatment options for neurodegenerative diseases. In this review, we focus on mitochondrial proteins that are directly associated with mitochondrial dysfunction. We also examine recently identified small molecule modulators of these mitochondrial targets and assess their potential in research and therapeutic applications. PMID- 26806042 TI - Digestive Enzyme Supplementation in Gastrointestinal Diseases. AB - BACKGROUND: Digestive enzymes are able to break down proteins and carbohydrates and lipids, and their supplementation may play a role in the management of digestive disorders, from lactose intolerance to cystic fibrosis. To date, several formulations of digestive enzymes are available on the market, being different each other in terms of enzyme type, source and origin, and dosage. METHODS: This review, performed through a non-systematic search of the available literature, will provide an overview of the current knowledge of digestive enzyme supplementation in gastrointestinal disorders, discussion of the use of pancreatic enzymes, lactase (beta-galactosidase) and conjugated bile acids, and also exploring the future perspective of digestive enzyme supplementation. RESULTS: Currently, the animal-derived enzymes represent an established standard of care, however the growing study of plant-based and microbe-derived enzymes offers great promise in the advancement of digestive enzyme therapy. CONCLUSION: New frontiers of enzyme replacement are being evaluated also in the treatment of diseases not specifically related to enzyme deficiency, whereas the combination of different enzymes might constitute an intriguing therapeutic option in the future. PMID- 26806045 TI - Increases in plasma plant sterols stabilize within four weeks of plant sterol intake and are independent of cholesterol metabolism. AB - BACKGROUND AND AIMS: Plant sterols (PS) lower plasma LDL-cholesterol through partial inhibition of intestinal cholesterol absorption. Although PS themselves are poorly absorbed, increased intakes of PS result in elevated plasma concentrations. In this paper, we report time curves of changes in plasma PS during 12 weeks of PS intake. Furthermore, the impact of cholesterol synthesis and absorption on changes in plasma PS is explored. METHODS AND RESULTS: The study was a double-blind, randomized, placebo-controlled, parallel-group study with the main aim to investigate the effects of PS on vascular function (clinicaltrials.gov: NCT01803178). Hypercholesterolemic but otherwise healthy men and women (n = 240) consumed low-fat spreads without or with added PS (3 g/d) for 12 weeks after a 4-week run-in period. Blood sampling was performed at week 0, 4, 8 and 12. Basal cholesterol-standardized concentrations of lathosterol and sitosterol + campesterol were used as markers of cholesterol synthesis and absorption, respectively. In the PS group, plasma sitosterol and campesterol concentrations increased within the first 4 weeks of intervention by 69% (95%CI: 58; 82) starting at 7.2 MUmol/L and by 28% (95%CI: 19; 39) starting at 11.4 MUmol/L, respectively, and remained stable during the following 8 weeks. Placebo corrected increases in plasma PS were not significantly different between high and low cholesterol synthesizers (P-values >0.05). Between high and low cholesterol absorbers, no significant differences were observed, except for the cholesterol-standardized sum of four major plasma PS (sitosterol, campesterol, brassicasterol and stigmasterol) showing larger increases in low absorbers (78.3% (95%CI: 51.7; 109.5)) compared to high absorbers (40.8% (95%CI: 19.9; 65.5)). CONCLUSIONS: Increases in plasma PS stabilize within 4 weeks of PS intake and do not seem impacted by basal cholesterol synthesis or absorption efficiency. This study was registered at clinicaltrials.gov (NCT01803178). PMID- 26806046 TI - Human nasal epithelial cells derived from multiple subjects exhibit differential responses to H3N2 influenza virus infection in vitro. PMID- 26806047 TI - Cluster analysis and prediction of treatment outcomes for chronic rhinosinusitis. AB - BACKGROUND: Current clinical classifications of chronic rhinosinusitis (CRS) have weak prognostic utility regarding treatment outcomes. Simplified discriminant analysis based on unsupervised clustering has identified novel phenotypic subgroups of CRS, but prognostic utility is unknown. OBJECTIVE: We sought to determine whether discriminant analysis allows prognostication in patients choosing surgery versus continued medical management. METHODS: A multi institutional prospective study of patients with CRS in whom initial medical therapy failed who then self-selected continued medical management or surgical treatment was used to separate patients into 5 clusters based on a previously described discriminant analysis using total Sino-Nasal Outcome Test-22 (SNOT-22) score, age, and missed productivity. Patients completed the SNOT-22 at baseline and for 18 months of follow-up. Baseline demographic and objective measures included olfactory testing, computed tomography, and endoscopy scoring. SNOT-22 outcomes for surgical versus continued medical treatment were compared across clusters. RESULTS: Data were available on 690 patients. Baseline differences in demographics, comorbidities, objective disease measures, and patient-reported outcomes were similar to previous clustering reports. Three of 5 clusters identified by means of discriminant analysis had improved SNOT-22 outcomes with surgical intervention when compared with continued medical management (surgery was a mean of 21.2 points better across these 3 clusters at 6 months, P < .05). These differences were sustained at 18 months of follow-up. Two of 5 clusters had similar outcomes when comparing surgery with continued medical management. CONCLUSION: A simplified discriminant analysis based on 3 common clinical variables is able to cluster patients and provide prognostic information regarding surgical treatment versus continued medical management in patients with CRS. PMID- 26806048 TI - The microbial environment and its influence on asthma prevention in early life. AB - There is accumulating evidence to suggest that the environmental microbiome plays a significant role in asthma development. The very low prevalence of asthma in populations highly exposed to microbial environments (farm children and Amish populations) highlights its preventive potential. This microbial diversity might be necessary to instruct a well-adapted immune response and regulated inflammatory responses to other inhaled and ingested environmental elements, such as allergens, particles, and viruses. Like the internal gut microbiome, which is increasingly recognized as an important instructor of immune maturation, the external environmental microbiome might shape immune responses on the skin, airway mucosal surfaces, and potentially also the gut early in life. The diversity of the external microbial world will ensure that of the many maladapted pathways leading to asthma development, most, if not all, will be counterbalanced. Likewise, important contributors to asthma, such as allergen sensitization and allergic manifestations early in life, are being suppressed. Thus the facets of innate immunity targeted by microbes and their compounds and metabolites might be the master switch to asthma and allergy protection, which has been found in environments rich in microbial exposures. PMID- 26806049 TI - Anaphylaxis in children and adolescents: The European Anaphylaxis Registry. AB - BACKGROUND: Anaphylaxis in children and adolescents is a potentially life threatening condition. Its heterogeneous clinical presentation and sudden occurrence in virtually any setting without warning have impeded a comprehensive description. OBJECTIVE: We sought to characterize severe allergic reactions in terms of elicitors, symptoms, emergency treatment, and long-term management in European children and adolescents. METHODS: The European Anaphylaxis Registry recorded details of anaphylaxis after referral for in-depth diagnosis and counseling to 1 of 90 tertiary allergy centers in 10 European countries, aiming to oversample the most severe reactions. Data were retrieved from medical records by using a multilanguage online form. RESULTS: Between July 2007 and March 2015, anaphylaxis was identified in 1970 patients younger than 18 years. Most incidents occurred in private homes (46%) and outdoors (19%). One third of the patients had experienced anaphylaxis previously. Food items were the most frequent trigger (66%), followed by insect venom (19%). Cow's milk and hen's egg were prevalent elicitors in the first 2 years, hazelnut and cashew in preschool-aged children, and peanut at all ages. There was a continuous shift from food- to insect venom- and drug-induced anaphylaxis up to age 10 years, and there were few changes thereafter. Vomiting and cough were prevalent symptoms in the first decade of life, and subjective symptoms (nausea, throat tightness, and dizziness) were prevalent later in life. Thirty percent of cases were lay treated, of which 10% were treated with an epinephrine autoinjector. The fraction of intramuscular epinephrine in professional emergency treatment increased from 12% in 2011 to 25% in 2014. Twenty-six (1.3%) patients were either admitted to the intensive care unit or had grade IV/fatal reactions. CONCLUSIONS: The European Anaphylaxis Registry confirmed food as the major elicitor of anaphylaxis in children, specifically hen's egg, cow's milk, and nuts. Reactions to insect venom were seen more in young adulthood. Intensive care unit admissions and grade IV/fatal reactions were rare. The registry will serve as a systematic foundation for a continuous description of this multiform condition. PMID- 26806053 TI - Comparison of Superb Micro-Vascular Ultrasound Imaging (SMI) and Contrast Enhanced Ultrasound (CEUS) for Detection of Endoleaks After Endovascular Aneurysm Repair (EVAR). AB - BACKGROUND: High-resolution contrast-enhanced ultrasound is one of methods used in the detection and characterization of endoleaks, which is a frequent complication after EVAR. A new technology provided by Toshiba's AplioTM 500 ultrasound system, called Superb Micro-Vascular Imaging (SMI), is dedicated specifically to imaging very low flow states and appears to be a promising new method for detection of endoleaks. CASE REPORT: After endovascular treatment, a 68-year-old patient who had stent-graft implantation underwent clinical examinations, including contrast-enhanced ultrasound (CEUS), superb micro vascular imaging (SMI), and computed tomographic angiography (CTA), revealing additional information about abnormal blood flow localized in the periphery of the sack of the left common iliac artery aneurysm. By using CEUS and SMI, the endoleak was clearly visible. CONCLUSIONS: This case report illustrates the potential clinical value of this advanced Doppler technology (SMI) and how it could influence clinical management. PMID- 26806052 TI - Cortical and trabecular deterioration in mouse models of Roux-en-Y gastric bypass. AB - Roux-en-Y gastric bypass (RYGB) is a profoundly effective treatment for severe obesity, but results in significant bone loss in patients. Developing a murine model that recapitulates this skeletal phenotype will provide a robust tool with which to study the physiologic mechanisms of this bone loss. We studied adult male C57BL/6J mice who underwent either RYGB or sham operation. Twelve weeks after surgery, we characterized biochemical bone markers (parathyroid hormone, PTH; C-telopeptide, CTX; and type 1 procollagen, P1NP) and bone microarchitectural parameters as measured by microcomputed tomography. RYGB treated mice had significant trabecular and cortical bone deficits compared with sham-operated controls. Although adjustment for final body weight eliminated observed cortical differences, the trabecular bone volume fraction remained significantly lower in RYGB mice even after weight adjustment. PTH levels were similar between groups, but RYGB mice had significantly higher indices of bone turnover than sham controls. These data demonstrate that murine models of RYGB recapitulate patterns of bone loss and turnover that have been observed in human clinical studies. Future studies that exploit this murine model will help delineate the alterations in bone metabolism and mechanisms of bone loss after RYGB. PMID- 26806055 TI - Maculopapular type drug eruption caused by silodosin. PMID- 26806056 TI - Right middle lobe atelectasis in children with asthma and prognostic factors. AB - BACKGROUND: Although right middle lobe (RML)-atelectasis of the lungs is a common complication of asthma, the relevant data is limited. The aim of this study is to define the characteristics of RML atelectasis in asthma during childhood. METHODS: Children with asthma who had recently developed RML atelectasis were included; anti-inflammatory medications, clarithromycin, and inhaled salbutamol were prescribed, chest-physiotherapy (starting on the sixth day) was applied. Patients were reevaluated on the sixth, fourteenth, thirtieth, and ninetieth days, chest X-rays were taken if the atelectasis had not resolved at the time of the previous visit. RESULTS: Twenty-seven patients (6.8 (4.8-8.3) years, 48.1% male) with RML atelectasis were included. Symptoms started 15 (7-30) days before admission. The thickness of the atelectasis was 11.8 +/- 5.8 mm; FEV1% was 75.9 +/- 14.2 and Childhood Asthma Control Test scores were 11.8 +/- 5.6 at the time of admission. The atelectasis had been resolved by the sixth (n = 3), fourteenth (n = 9), thirtieth (n = 10), and ninetieth days (n = 3). The treatment response of the patients whose atelectasis resolved in fourteen days was better on the sixth-day (atelectasis thickness: 4.7 +/- 1.7 vs. 11.9 +/- 7.3 mm, p = 0.021) compared to those whose atelectasis resolved later. Nearly half (54.5%) of the patients whose atelectasis had resolved by fourteen days were using controller medications at the time of admission. However, only two patients (13.3%) were on controller treatment in the latter group (p = 0.032). Regression analysis didn't reveal any prognostic factors for the early resolution of atelectasis. CONCLUSIONS: Early diagnosis and treatment of RML atelectasis prevents complications. Patients who had early resolution of atelectasis had already been on anti-inflammatory medications, and responded better to aggressive treatment within the first week. PMID- 26806057 TI - Increase in autoimmune pulmonary alveolar proteinosis after the 2011 Fukushima disaster. PMID- 26806058 TI - Leptin expression in mandarin fish Siniperca chuatsi (Basilewsky): Regulation by postprandial and short-term fasting treatment. AB - Most fish species possess duplicate leptin genes (LEP). Mandarin fish (Siniperca chuatsi) leptin A gene (sLEP-A) have been cloned in the previous study. In the present study, we cloned and characterized leptin B gene (sLEP-B) in mandarin fish, including a 471bp open reading frame (ORF) encoding a 158-amino acid protein. The three-dimensional (3D) structural model of sLEP-B protein showed a highly conserved of tertiary structure similar to that of other vertebrates. Genomic sequencing results indicated that sLEP-B possessed only one intron. This is the first report of the loss of an intron in LEP-B in Perciformes. The different distribution patterns of sLEPs suggest different physiological roles of these two genes. The presence of HNF3beta, a liver-enriched transcription factor, only in sLEP-A indicated abundant expression and metabolic function of sLEP-A in the liver. In an in vivo experiment, the expressions of brain sLEP-A and sLEP-B were observed to increase after a meal. During the short-term fasting, the expressions of sLEPs in mandarin fish brain were decreased significantly. A persistent and significant increase in hepatic sLEP-A expression supported a relationship between leptin and food intake in mandarin fish. These results suggest that sLEP-A plays an important role in the regulation of energy homeostasis in this carnivorous fish, and sLEP-B is probably a specialized gene responsible for the central nervous system (CNS) control of energy regulation. PMID- 26806059 TI - Water deprivation up-regulates urine osmolality and renal aquaporin 2 in Mongolian gerbils (Meriones unguiculatus). AB - To better understand how desert rodents adapt to water scarcity, we examined urine osmolality, renal distribution and expression of aquaporins (AQPs) in Mongolian gerbils (Meriones unguiculatus) during 7 days of water deprivation (WD). Urine osmolality of the gerbils during WD averaged 7503 mOsm kg(-1). Renal distributions of AQP1, AQP2, and AQP3 were similar to that described in other rodents. After the 7 day WD, renal AQP2 was up-regulated, while resting metabolic rate and total evaporative water loss decreased by 43% and 36%, respectively. Our data demonstrated that Mongolian gerbils showed high urine concentration, renal AQPs expression and body water conservation to cope with limited water availability, which may be critical for their survival during dry seasons in cold deserts. PMID- 26806060 TI - Multidisciplinary Approach for Acromegaly: A Single Tertiary Center's Experience. AB - BACKGROUND: Acromegaly is a multisystemic disease that requires a multidisciplinary approach. The aim of this study was to determine early and late remissions of patients who underwent surgery at our center and to evaluate relations between pathologic and radiologic properties of adenoma and medical and radiosurgical treatments with remissions. METHODS: The medical records of 103 patients with acromegaly who underwent endoscopic endonasal transsphenoidal surgery in Cerrahpasa Medical Faculty, Istanbul University, between 2007 and 2014 were reviewed. Clinical, biochemical, radiologic, and pathologic properties were determined. RESULTS: The total median follow-up time was 38 months [interquartile range: 24-53.5 months]. Thirty-two percent of the adenomas were microadenomas and 68% were macroadenomas The early remission rate was 51.5% and late remission was 75.2%. The sellar floor invasion was significantly lower in patients with early and late remissions (P = 0.01 and P = 0.009, respectively). The initial growth hormone (GH; P < 0.001), first-day GH (P = 0.03), 3-month GH (P = 0.001), insulin like growth factor-1 (P = 0.004), and 6-month insulin-like growth factor-1 (P = 0.02) levels were significantly greater in patients with sellar floor invasion. The late remission rates (P = 0.004) were greter and reoperation needs (P = 0.05) were lower in patients with Ki-67 <3% than in patients with >=3%. Seventy (68.6%) patients needed medical therapy during follow-up. CONCLUSIONS: Late remission was achieved using a multidiciplinary approach in 75.2% of 103 patients with acromegaly, and young age, male sex, high Ki-67 and mitosis indices, and cavernous sinus and sellar-floor invasion had negative effects on clinical and biochemical control of the disease. PMID- 26806061 TI - Simultaneous or Early Sequential Rupture of Multiple Intracranial Aneurysms: A Rare and Insufficiently Understood Entity. AB - BACKGROUND: Simultaneous or early sequential rupture of multiple intracranial aneurysms (MIAs) is encountered rarely, with no more than 10 cases having been reported. As a result of its rarity, there are a lot of questions concerning this entity need to be answered. CASE DESCRIPTION: A 67-year-old woman was admitted to the First Hospital of Jilin University (Eastern Division) from a local hospital after a sudden onset of severe headache, nausea, and vomiting. Head computed tomography (CT) at the local hospital revealed diffuse subarachnoid hemorrhage (SAH) that was concentrated predominately in the suprasellar cistern and interhemispheric fissure. During her transfer to our hospital, she experienced another episode of sudden headache. CT on admission to our hospital revealed that the SAH was increased with 2 isolated hematomas both in the interhemispheric fissure and the left paramedian frontal lobe. Further CT angiography and intraoperative findings were in favor of early sequential rupture of 2 intracranial aneurysms. To further elucidate the characteristics, mechanism, management, and prognosis of this specific entity, we conducted a comprehensive review of the literature. CONCLUSIONS: The mechanism of simultaneous or early sequential rupture of MIAs is still obscure. Transient elevation of blood pressure might play a role in the process, and preventing the sudden elevation of blood pressure might be beneficial for patients with aneurysmal SAH and MIAs. The management of simultaneously or early sequentially ruptured aneurysms is more complex for its difficulty in responsible aneurysm determination, urgency in treatment, toughness in intraoperative manipulation and poorness in prognosis. PMID- 26806062 TI - Retrograde Suction Decompression for Clip Occlusion of Internal Carotid Artery Communicating Segment Aneurysms. AB - BACKGROUND: Retrograde suction decompression (RSD) can achieve proximal parent vessel control, improve aneurysm neck visualization, and allow parent vessel reconstruction for direct clipping of internal carotid artery (ICA) aneurysms. The aim of the present study was to describe the technique and surgical results of RSD for direct clipping of ICA communicating segment (C1) aneurysms. METHODS: The clinical data and treatment summaries of 20 patients who underwent RSD assisted clipping of ICA C1 aneurysms were retrospectively reviewed. Pre- and postoperative three- or four-dimensional computed tomography angiograms, postoperative magnetic resonance images, surgical notes, operative complications, and outcomes were assessed. RESULTS: All patients except one harbored unruptured C1 aneurysms. Extracranial-intracranial graft bypass using the radial artery was performed in five patients. Fifteen patients required temporary clipping of the posterior communicating artery for further reduction of blood back-flow into the aneurysm. All aneurysms were successfully clipped and postoperative three- or four-dimensional computed tomography angiography revealed no major branch occlusion or residual aneurysm. At the 6-month follow-up examination, 19 patients had a good outcome and 1 patient had poor outcome associated with anterior choroidal artery ischemia. No death had occurred at 6-month follow-up examination. CONCLUSIONS: The RSD technique is a useful procedure to achieve proximal vascular control, to soften and shrinkage the aneurysm sac, and to provide a wide and clean operative field allowing safe clip placement. The RSD technique requires special attention to the relationship between the perforators and the aneurysm, and close cooperation between the surgeon and the assistant. PMID- 26806063 TI - Clinical and Angiographic Features of Patients with Moyamoya Disease and the p.R4810K Heterozygous Variant. AB - OBJECTIVE: To elucidate the clinical and angiographic features in patients with moyamoya disease (MMD) and the p.R4810K heterozygous variant and present an angiographic grading system to evaluate disease severity. METHODS: We retrospectively reviewed 87 patients with MMD and the p.R4810K variant treated at Beijing Tiantan Hospital. Clinical features, stroke subtype, and angiographic characteristics were analyzed. RESULTS: The median age at diagnosis was 25 years (range, 3-59). The ratio of women to men was 1.2:1. The familial occurrence of MMD was 14.9%. The primary symptom at diagnosis was ischemia, hemorrhage, or other in 67, 16, and 4 patients, respectively. Angiographic features correlating with ischemic stroke or stroke, including Suzuki grade, external carotid artery collaterals, leptomeningeal collaterals, and Mugikura grade, were identified. A binary logistic regression model demonstrated a significant correlation of Suzuki grade (P = 0.008) and posterior cerebral artery grade (P = 0.029) with ischemic stroke (142 hemispheres). A modified Suzuki-Mugikura grading system was developed. The areas under the receiver operating characteristic curves used to predict ischemic stroke based on the Suzuki grading, Mugikura grading, and modified Suzuki-Mugikura grading systems were 0.736, 0.69, and 0.741, respectively. Furthermore, the modified Suzuki-Mugikura grades were significantly correlated with infarction in posterior circulation and the number of infarcted regions. CONCLUSIONS: The clinical and angiographic features of a Chinese MMD population with the p.R4810K variant were similar to those of a Japanese MMD population; they might be a distinct cerebrovascular disease entity and represent a separate subgroup. A modified Suzuki-Mugikura grading system was valuable for predicting stroke and evaluating disease severity. PMID- 26806064 TI - Measuring Quality of Neurosurgical Care: Readmission Is Affected by Patient Factors. AB - OBJECTIVE: The Hospital Readmission Reduction Program section of the Patient Protection and Affordable Care Act uses readmission rates as a proxy for measuring quality of care. Multiple studies have demonstrated that readmission rates are highly imprecise proxies for quality of care because readmission rates contain large amounts of statistical noise and are dependent on disease type, insurance type, severity, population, and a multitude of other factors. The current study was conducted to investigate characteristics associated with readmission and the quality of neurosurgical care. METHODS: Admissions data were gleaned from the University Health System Consortium database for neurosurgical patient (both cranial and spine) readmissions to assess patient-related factors relating to readmission from January 2011 to December 2014. RESULTS: Among 257,212 admissions for neurosurgical disease analyzed, patients with Medicaid and private payers as a primary insurance source had increased rates of readmission (odds ratio for readmission of 1.38 and 1.17, respectively) compared with patients with Medicare or other primary insurers. Patients with greater severity of disease and emergent or urgent admission also had statistically significant rates of readmission. CONCLUSIONS: The findings suggest that readmission is affected by patient factors that are beyond the control of treating physicians. These findings also suggest that readmission rates may not be a good proxy for measurement of quality of care in neurosurgical patients. PMID- 26806065 TI - Guideline Adherence and Outcomes in Severe Adult Traumatic Brain Injury for the CHIRAG (Collaborative Head Injury and Guidelines) Study. AB - We examined the effect of early intensive care unit (ICU) adherence to 2007 Brain Trauma Foundation Guideline indicators after traumatic brain injury (TBI) on inpatient mortality at a level 1 trauma center in India (Jay Prakash Narayan Apex Trauma Center [JPNATC]) and Harborview Medical Center (HMC) in U.S. among adults older than 18 years with severe TBI. At each site, ICU Guideline adherence in first 72 hours for 17 indicators was determined and expressed as a percentage. Outcomes were in-hospital mortality and Glasgow Outcome Scale (GOS) scores at 3, 6, and 12 months after discharge. JPNATC and HMC Guideline adherence rates were 74.9% [11.0] and 71.6 % (SD +/-10.4), and overall in-hospital mortality was 24% and 27%, respectively. At JPNATC, less than 65% ICU Guideline adherence was associated with higher inpatient mortality (adjusted relative risk [aRR], 1.92; 95% confidence interval [CI], 1.11-3.33) and an increase in ICU Guideline adherence rate by 1% was associated with a 3% lower in-hospital mortality (aRR, 0.97; 95% CI, 0.95-0.99). Among patients discharged with a GOS score of 2-4 at JPNATC, 67% improved at 12 months (R(2) = 0.991; P < 0.01; 99% follow-up rate) compared with discharge, but 35%, 25%, and 14% of patients discharged with a GOS score of 3-5 deteriorated at 3, 6, and 12 months to a lower GOS at home. Achieving early ICU adherence to guideline indicators was feasible and associated with significantly lower in-hospital mortality at JPNATC. Although the intracranial pressure (ICP) monitoring rates varied, in-hospitals deaths were similar between the two institutions. Although long-term outcomes generally improved, patients discharged with favorable GOS score often deteriorated at home. PMID- 26806066 TI - The Expanded Endoscopic Endonasal Approach to Anterior Communicating Artery Aneurysms: A Cadaveric Morphometric Study. AB - OBJECTIVE: The purpose of this study was to explore the endoscopic endonasal approach to the anterior communicating artery complex. DESIGN: Anatomic, morphometric analysis of human cadaver heads. SUBJECTS: Fifteen latex-injected adult cadaver heads. MAIN OUTCOME MEASURES: The anatomic boundaries of the operative field and the dimensions of exposure of the anterior communicating artery (ACoA) complex were measured and clip placement feasibility was assessed. RESULTS: Exposure of the ACoA and bilateral A1 and A2 segments was accomplished in all 15 cadaver heads. Average length of the exposed ACoA was 3 +/- 1 mm, the left A1 was 5 +/- 3 mm and right A1 was 5 +/- 1 mm, while the A2 segment was 5 +/ 2 mm bilaterally. The average distance from the alar floor to the ACoA was 95 mm, while proximal lateral limit measured between the alar floor margins was 36 mm. The distal lateral limit as defined by the distance between the lateral most exposed margins of the chiasm was 19 mm. Clip placement was accomplished for the ACoA and the A1 and A2 segments bilaterally in all specimens. CONCLUSION: The endoscopic, endonasal transtuberculum, transplanum approach is an anatomically feasible alternative to treating select aneurysms of the ACoA complex. PMID- 26806067 TI - Flow Diversion and Middle Cerebral Artery Aneurysms: Is Successful Aneurysm Occlusion Dependent on Branch Occlusion? PMID- 26806068 TI - Basic Statistical Shortcomings Can Induce Mistaken Interpretation of Neurosurgical Articles. PMID- 26806069 TI - Anisotropic magnetic entropy change in RFeO3 single crystals (R = Tb, Tm, or Y). AB - Compared with traditional gas-compression/expansion refrigeration, magnetic refrigeration based on magnetocaloric effect (MCE) exhibits the advantages of high energy efficiency and environment friendliness. Here, we created large MCE in RFeO3 (R = Tb or Tm) single crystals by the magnetization vector rotation of single crystal with strong magnetocrystalline anisotropy (MCA), rather than merely via the order-disorder magnetic phase transition or magnetic structural transition. Owing to the difference in charge distribution of 4f-electrons between Tb(3+) and Tm(3+) ions, the rotating field entropy with different signs, DeltaSM(R) = 17.42 J/kg K, and -DeltaSM(R) = -9.01 J/kg K are achieved at 9 K and 17 K for TbFeO3 and TmFeO3 single crystals from b axis to c axis, at 50 kOe, respectively. The finding of the large anisotropic MCE not only advances our understanding of the anisotropy of MCE, but also extends the application for single crystals to magnetic refrigeration. PMID- 26806071 TI - Genetically anchored fluorescent probes for subcellular specific imaging of hydrogen sulfide. AB - Imaging hydrogen sulfide (H2S) at the subcellular resolution will greatly improve the understanding of functions of this signaling molecule. Taking advantage of the protein labeling technologies, we report a general strategy for the development of organelle specific H2S probes, which enables sub-cellular H2S imaging essentially in any organelles of interest. PMID- 26806073 TI - Simultaneous measurements of on-road/in-vehicle nanoparticles and NOx while driving: Actual situations, passenger exposure and secondary formations. AB - Simultaneous measurements of on-road and in-vehicle NO and NO2 levels, particle number concentrations (PNCs), and particles size distributions were performed while driving using a test vehicle equipped with real-time sensors. The results obtained on regional roads showed that heavy-duty vehicles in traffic seem to have a major impact on on-road air quality. Measurements on highways that included a 10km tunnel and a 2km uphill section of road indicated that sub-50nm particles have different features from the other species because of their higher volatility. The other species showed quite high on-road concentrations in the tunnel. In-vehicle conditions were made similar to the on-road ones by setting the air conditioning (AC) mode to the fresh air mode. The in-vehicle NO2 concentration in the tunnel was over 0.50ppmV, which is almost five times higher than the 1-hour ambient air quality standard proposed by the World Health Organization (WHO). In sections other than the tunnel, the in-vehicle NO2 concentration was almost the same as the 1-hour WHO standard. Higher on-road NO2/NOx ratios than those of exhaust gases and different behavior of sub-50nm particles from other species suggested that NO2 and sub-50nm particles were mainly due to secondary products formed by atmospheric reactions. PMID- 26806072 TI - Magnetite nanoparticle (NP) uptake by wheat plants and its effect on cadmium and chromium toxicological behavior. AB - The aim of this work was to assess the uptake of citrate-coated magnetite nanoparticles (NPs) by wheat plants and its effect on the bioaccumulation and toxicity of individual and joint Cd(2+) and Cr(6+) levels. Seven-day assays were conducted using quartz sand as the plant growth substrate. The endpoints measured were seed germination, root and shoot lengths, and heavy metal accumulation. Magnetite exhibited very low toxicity, regardless of the wheat seedling NP uptake and distribution into roots and shoots. The seed germination and shoot length were not sensitive enough, while the root length was a more sensitive toxicity endpoint. The root length of wheat seedlings exposed to individual metals decreased by 50% at 2.67mgCd(2)(+)kg(-1) and 5.53mgCr(6+)kg(-1). However, when magnetite NPs (1000mgkg(-1)) were added, the root length of the plants increased by 25 and 50%. Cd(2+) and Cr(6+) showed similar and noninteractive joint action, but strongly impaired the wheat seedlings. In contrast, an interactive infra additive or antagonistic effect was observed upon adding magnetite NPs. Thus, cadmium and chromium accumulation in vegetable tissues was considerately diminished and the toxicity alleviated. PMID- 26806074 TI - Are lichens potential natural reservoirs for plant pathogens? PMID- 26806075 TI - Duncan F. Gregory, William Walton and the development of British algebra: 'algebraical geometry', 'geometrical algebra', abstraction. AB - This paper provides a detailed account of the period of the complex history of British algebra and geometry between the publication of George Peacock's Treatise on Algebra in 1830 and William Rowan Hamilton's paper on quaternions of 1843. During these years, Duncan Farquharson Gregory and William Walton published several contributions on 'algebraical geometry' and 'geometrical algebra' in the Cambridge Mathematical Journal. These contributions enabled them not only to generalize Peacock's symbolical algebra on the basis of geometrical considerations, but also to initiate the attempts to question the status of Euclidean space as the arbiter of valid geometrical interpretations. At the same time, Gregory and Walton were bound by the limits of symbolical algebra that they themselves made explicit; their work was not and could not be the 'abstract algebra' and 'abstract geometry' of figures such as Hamilton and Cayley. The central argument of the paper is that an understanding of the contributions to 'algebraical geometry' and 'geometrical algebra' of the second generation of 'scientific' symbolical algebraists is essential for a satisfactory explanation of the radical transition from symbolical to abstract algebra that took place in British mathematics in the 1830s-1840s. PMID- 26806076 TI - The nomological image of nature: explaining the tide in the thirteenth century. AB - The paper examines the relevance of the nomological view of nature to three discussions of tide in the thirteenth century. A nomological conception of nature assumes that the basic explanatory units of natural phenomena are universally binding rules stated in quantitative terms. (1) Robert Grosseteste introduced an account of the tide based on the mechanism of rarefaction and condensation, stimulated by the Moon's rays and their angle of incidence. He considered the Moon's action over the sea an example of the general efficient causality exerted through the universal activity of light or species. (2) Albert the Great posited a plurality of causes which cannot be reduced to a single cause. The connaturality of the Moon and the water is the only principle of explanation which he considered universal. Connaturality, however, renders neither formulation nor quantification possible. While Albert stressed the variety of causes of the tide, (3) Roger Bacon emphasized regularity and reduced the various causes producing tides into forces. He replaced the terminology of 'natures' by one of 'forces'. Force, which in principle can be accurately described and measured, thus becomes a commensurable aspect of a diverse cosmos. When they reasoned why waters return to their place after the tide, Grosseteste argued that waters return in order to prevent a vacuum, Albert claimed that waters 'follow their own nature', while Bacon held that the 'proper force' of the water prevails over the distant force of the first heaven. I exhibit, for the thirteenth century, moments of the move away from the Aristotelian concerns. The basic elements of these concerns were essences and natures which reflect specific phenomena and did not allow for an image of nature as a unified system. In the new perspective of the thirteenth century the key was a causal link between the position of the Moon and the tide cycle, a link which is universal and still qualitative, yet expressed as susceptible to quantification. PMID- 26806077 TI - Use of a lyophilized bovine pericardium graft to repair tunical defect in patients with Peyronie's disease: experience in a clinical setting. AB - Many different materials are available for grafting during surgery for Peyronie's disease (PD). To study the outcomes associated with the use of a lyophilized bovine pericardium graft (Peri-Guard(r)) to repair tunical defects in patients with PD, descriptive study of 43 patients with disabling penile curvature was performed. Curvature was measured before and after the intervention using a standardized procedure. Surgical technique was plaque excision and grafting of the tunical defect carried out by a single surgeon. A lyophilized bovine pericardium patch was used for grafting. We measured the change in penile curvature and length, the ability to perform successful sexual intercourse without further pharmacological or surgical treatment, and the satisfaction with treatment. Follow-up data were available for a total of 41 patients. Median age was 50 years (IQR 48-52); mean follow-up time was 14 +/- 6 months. Complete penile straightening was achieved in 33 patients (80.5%) and five patients (12.2%) had curvature under 20 degrees . Three months after surgery and stretching therapy, mean (s.d.) flaccid penile length increased from 11.2 +/- 2.8 cm to 12.1 +/- 2.9 cm (P = 0.062). Seventy-five percentage of patients reported being able to achieve successful intercourse without further treatment. Eighty five percentage of patients reported to be satisfied with the treatment. There was no evidence of tissue rejection or infection, and only four patients suffered an adverse event. Plaque excision and grafting of the tunical defect with lyophilized bovine pericardium seems to be a safe and effective treatment for patients with PD. PMID- 26806078 TI - Recurrent varicocele. AB - Varicocele recurrence is one of the most common complications associated with varicocele repair. A systematic review was performed to evaluate varicocele recurrence rates, anatomic causes of recurrence, and methods of management of recurrent varicoceles. The PubMed database was evaluated using keywords "recurrent" and "varicocele" as well as MESH criteria "recurrent" and "varicocele." Articles were not included that were not in English, represented single case reports, focused solely on subclinical varicocele, or focused solely on a pediatric population (age <18). Rates of recurrence vary with the technique of varicocele repair from 0% to 35%. Anatomy of recurrence can be defined by venography. Management of varicocele recurrence can be surgical or via embolization. PMID- 26806079 TI - Bibliometrics: tracking research impact by selecting the appropriate metrics. AB - Traditionally, the success of a researcher is assessed by the number of publications he or she publishes in peer-reviewed, indexed, high impact journals. This essential yardstick, often referred to as the impact of a specific researcher, is assessed through the use of various metrics. While researchers may be acquainted with such matrices, many do not know how to use them to enhance their careers. In addition to these metrics, a number of other factors should be taken into consideration to objectively evaluate a scientist's profile as a researcher and academician. Moreover, each metric has its own limitations that need to be considered when selecting an appropriate metric for evaluation. This paper provides a broad overview of the wide array of metrics currently in use in academia and research. Popular metrics are discussed and defined, including traditional metrics and article-level metrics, some of which are applied to researchers for a greater understanding of a particular concept, including varicocele that is the thematic area of this Special Issue of Asian Journal of Andrology. We recommend the combined use of quantitative and qualitative evaluation using judiciously selected metrics for a more objective assessment of scholarly output and research impact. PMID- 26806080 TI - Summary evidence on the effects of varicocele treatment to improve natural fertility in subfertile men. AB - The objective of this review was to summarize the evidence concerning the benefit of varicocele treatment to improve natural fertility in subfertile males. We also analyzed the effect of varicocele treatment on conventional semen parameters and sperm functional tests. An electronic search to collect the data was performed using the PubMed/MEDLINE databases until July 2015. Data pooled from a variety of study designs indicate that varicocelectomy improves semen parameters in the majority of the treated men with clinical varicocele and abnormal semen parameters regardless of the chosen surgical method. Surgical varicocele repair was beneficial not only for alleviating oxidative stress-associated infertility but also to improve sperm nuclear DNA integrity. However, given the low magnitude of the effect size in sperm DNA integrity, further research is needed to elucidate its clinical significance. Conflicting results on the effect of varicocele treatment on natural fertility seem to be due to heterogeneous study designs and, more importantly, patient selection criteria. When these issues are controlled, current evidence indicates that treatment of subclinical varicocele is not warranted, as it does not seem to improve fertility. On the contrary, fair evidence indicates that varicocele treatment should be offered to infertile patients with palpable varicocele and abnormal semen parameters. This evidence supports the current guidelines issued by the American Urological Association and European Association of Urology, which state that varicocele treatment should be offered to male partners of infertile couples presenting for evaluation with clinical varicocele and semen parameters alterations. PMID- 26806082 TI - Asymptomatic male currently not desiring fertility with bilateral subclinical varicocele found on ultrasound evaluation and borderline semen analysis results. PMID- 26806081 TI - The significance of clinical practice guidelines on adult varicocele detection and management. AB - Varicoceles are the most common correctable etiology of male factor infertility. However, the detection and management of varicoceles have not been standardized. This has led to decades of debate regarding the effect of varicocele on male infertility and subsequently whether repair leads to an improved fertility status. The current body of evidence investigating the role of varicocele and varicocelectomy is weak and conflicting. The stance taken by the AUA and ASRM suggests that there is insufficient outcomes data to support evidenced-based guidelines, citing evidence used to provide current recommendations are generally of a low quality level. On the other hand, the EAU Guidelines give a level 1a of evidence for management of varicoceles that are clinically palpable, associated with subnormal semen analyses and having otherwise unexplained fertility. Besides aiding with clinical varicocele detection and management, clinical practice opinion statements and guidelines aim to direct and strengthen the infrastructure of future studies. We review the current status of opinion statements and guidelines in varicocele and management detection with focus on their application in practice. PMID- 26806083 TI - Resolution of erectile dysfunction after an andrological visit in a selected population of patients affected by psychogenic erectile dysfunction. AB - The aim of this study was to ascertain whether some patients with psychogenic erectile dysfunction (PED) who chose psychotherapy spontaneously improved their sexual function immediately after diagnosis. Two hundred eighty-five patients with PED were retrospectively studied. Complete resolution of PED was analyzed regarding age, primary or secondary PED, marital status, domestic status, prevailing attitude of the female partner to the dysfunction, duration of their partnership, social status, duration of PED, International Index of Erectile Function score, and prevailing attitude of the patient after a diagnosis of PED. The data were analyzed using post-hoc tests. PED was resolved in 32.3% of the patients immediately after diagnosis. These patients were older, more frequently affected by secondary ED, more frequently living with their partner, and more frequently resigned or happy with the diagnosis of PED than the patients who did not resolve their PED. A nonchalant or cooperative female attitude to PED improved the possibility of PED resolution. The other variables did not influence PED resolution. Our data showed that a clear-cut diagnosis of psychogenic erectile deficiency and some psychosocial factors were critical for the management of some patients with PED. PMID- 26806084 TI - A missense mutation in the androgen receptor gene causing androgen insensitivity syndrome in a Chinese family. PMID- 26806085 TI - Comparison of the patient and partner satisfaction with 700CX and Titan penile prostheses. AB - Most widespread three-component penile prosthesis models are 700CXTM and Titan (r) . Our purpose is to assess patient and partner satisfaction after the first implant. This is a multicenter, retrospective, nonrandomized study in which all patients who met the inclusion criteria between 2009 and 2013 were included. In total, 248 patients agreed to participate. To evaluate patient satisfaction, a validated but modified 11-question questionnaire was completed (EDITS); and a nonvalidated two-item questionnaire was given to the partner. Statistical analysis used an ordinal logistic regression model. Two hundred and forty-eight patients (194 with 700CXTM vs 54 with Titan(r)) and 207 couples completed the questionnaire (165 with 700CXTM vs 42 with Titan(r)). Overall satisfaction was high. Both showed great reliability for sexual intercourse and high compliance with prior expectations. Most patients were able to manage the penile prosthesis correctly within 6 months. Postoperative penile shortening led to some dissatisfaction in 42% and 46% of cases (700CXTM /Titan(r)). Significant differences were found in three questions of patients' questionnaire. There were more patients satisfied with the 700CXTM (P = 0.0001). No patient with Titan(r) implant took longer than 6 months to optimal management. Only 4% of patients with 700CXTM implant were dissatisfied with the deflation, in contrast to 24% with the Titan(r) (P = 0.0031). Of the two partners' questions, one showed a statistically significant difference (P = 0.0026). It seems that group 700CXTM would recommend to re-implant the prosthesis with a greater tendency. The overall satisfaction was very high for both prostheses. The final aspect of the erected and flaccid penis was satisfactory, but both groups showed significant discontent with its final size. Partners' overall satisfaction was high. PMID- 26806086 TI - Damage to Olfactory Progenitor Cells Is Involved in Cigarette Smoke-Induced Olfactory Dysfunction in Mice. AB - Exposure to cigarette smoke is a major cause of olfactory dysfunction. However, the underlying mechanisms by which cigarette smoke interferes with the highly regenerative olfactory nerve system remain unclear. To investigate whether cigarette smoke induces olfactory dysfunction by disrupting cell proliferation and cell survival in the olfactory epithelium (OE), we developed a mouse model of smoking that involved intranasal administration of a cigarette smoke solution (CSS). Immunohistological analyses and behavioral testing showed that CSS administration during a period of 24 days reduced the number of olfactory marker protein-positive mature olfactory receptor neurons (ORNs) in the OE and induced olfactory dysfunction. These changes coincided with a reduction in the number of SOX2(+) ORN progenitors and Ki-67(+) proliferating cells in the basal layer of the OE, an increase in the number of caspase-3(+) apoptotic cells, and an increase in the expression of mRNA for the inflammatory cytokines IL-1beta and IL 6. Notably, the proliferating ORN progenitor population recovered after cessation of treatment with CSS, resulting in the subsequent restoration of mature ORN numbers and olfaction. These results suggest that SOX2(+) ORN progenitors are targets of CSS-induced impairment of the OE, and that by damaging the ORN progenitor population and increasing ORN death, CSS exposure eventually overwhelms the regenerative capacity of the epithelium, resulting in reduced numbers of mature ORNs and olfactory dysfunction. PMID- 26806088 TI - Selenium Alleviates Aflatoxin B1-Induced Immune Toxicity through Improving Glutathione Peroxidase 1 and Selenoprotein S Expression in Primary Porcine Splenocytes. AB - Selenium (Se) is generally known as an essential micronutrient and antioxidant for humans and animals. Aflatoxin B1 (AFB1) is a frequent contaminant of food and feed, causing immune toxicity and hepatotoxicity. Little has been done about the mechanisms of how Se protects against AFB1-induced immune toxicity. The aim of this present study is to investigate the protective effects of Se against AFB1 and the underlying mechanisms. The primary splenocytes isolated from healthy pigs were stimulated by anti-pig-CD3 monoclonal antibodies and treated by various concentrations of different Se forms and AFB1. The results showed that Se supplementation alleviated the immune toxicity of AFB1 in a dose-dependent manner, as demonstrated by increasing T-cell proliferation and interleukin-2 production. Addition of buthionine sulfoximine abrogated the protective effects of SeMet against AFB1. SeMet enhanced mRNA and protein expression of glutathione peroxidase 1 (GPx1), selenoprotein S (SelS), and thioredoxin reductase 1 without and with AFB1 treatments. Furthermore, knockdown of GPx1 and SelS by GPx1 specific siRNA and SelS-specific siRNA diminished the protective effects of SeMet against AFB1-induced immune toxicity. It is concluded that SeMet diminishes AFB1 induced immune toxicity through increasing antioxidant ability and improving GPx1 and SelS expression in splenocytes. This study suggests that organic selenium may become a promising supplementation to protect humans and animals against the decline in immunity caused by AFB1. PMID- 26806087 TI - Dermatomyositis With or Without Anti-Melanoma Differentiation-Associated Gene 5 Antibodies: Common Interferon Signature but Distinct NOS2 Expression. AB - The anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody is specifically associated with dermatomyositis (DM). Nevertheless, anti-MDA5(+) patients experience characteristic symptoms distinct from classic DM, including severe signs of extramuscular involvement; however, the clinical signs of myopathy are mild or even absent. The morphological and immunological features are not yet described in adulthood. Data concerning the pathophysiology of anti MDA5 DM are sparse; however, the importance of the interferon (IFN) type I pathway involved in DM has been shown. Our aim was to define morphological alterations of the skeletal muscle and the intrinsic immune response of anti-MDA5 positive DM patients. Immunohistological and RT-PCR analysis of muscle biopsy specimens from anti-MDA5 and classic DM were compared. Those with anti-MDA5 DM did not present the classic features of perifascicular fiber atrophy and major histocompatibility complex class I expression. They did not show significant signs of capillary loss; tubuloreticular formations were observed less frequently. Inflammation was focal, clustering around single vessels but significantly less intense. Expression of IFN-stimulated genes was up-regulated in anti-MDA5 DM; however, the IFN score was significantly lower. Characteristic features were observed in anti-MDA5 DM and not in classic DM patients. Only anti MDA5 DM showed numerous nitric oxide synthase 2-positive muscle fibers with sarcoplasmic colocalization of markers of regeneration and cell stress. Anti-MDA5 positive patients demonstrate a morphological pattern distinct from classic DM. PMID- 26806090 TI - Identification of Au-S complexes on Au(100). AB - Using a combination of scanning tunneling microscopy and density functional theory (DFT) calculations, we have identified a set of related Au-S complexes that form on Au(100), when sulfur adsorbs and lifts the hexagonal surface reconstruction. The predominant complex is diamond-shaped with stoichiometry Au4S5. All of the complexes can be regarded as combinations of S-Au-S subunits. The complexes exist within, or at the edges of, p(2 * 2) sulfur islands that cover the unreconstructed Au regions, and are observed throughout the range of S coverage examined in this study, 0.009 to 0.12 monolayers. A qualitative model is developed which incorporates competitive formation of complexes, Au rafts, and p(2 * 2) sulfur islands, as Au atoms are released by the surface structure transformation. PMID- 26806089 TI - Obstetrical brachial plexus palsy: Can excision of upper trunk neuroma and nerve grafting improve function in babies with adequate elbow flexion at nine months of age? AB - Accepted indications for exploration in obstetrical brachial plexus palsy (OBPP) vary by center. Most agree that full elbow flexion against gravity at nine months of age implies high chance of spontaneous recovery and thus excludes a baby from surgical intervention. However, there are certain movements of the shoulder and forearm that may not be used frequently by the infant, but are extremely important functionally as they grow. These movements are difficult to assess in a baby and may lead to some clinicians to recommend conservative treatment, when this cohort of infants may in fact benefit substantially from surgery. A retrospective review was conducted on all infants managed surgically at the Brachial Plexus Center of a major children's hospital from 2009 to 2014. Further analysis identified five patients who had near-normal AMS scores for elbow flexion but who had weakness of shoulder abduction, flexion, external rotation, and/or forearm supination. In contrast to standard conservative management, this cohort underwent exploration, C5-6 neuroma excision, and sural nerve grafting. Data analysis was performed on this group to look for overall improvement in function. During an average follow-up period of 29 months, all patients made substantial gains in motor function of the shoulder and forearm, without loss of elbow flexion or extension, or worsening of overall outcome. In select infants with brachial plexus injuries but near-normal AMS scores for elbow flexion, surgical intervention may be indicated to achieve the best functional outcome. PMID- 26806091 TI - Special Needs: Scholastic Disability Accommodations from K-12 and Transitions to Higher Education. AB - The number of students entering post-secondary education with already diagnosed disabilities is on the rise and mirrors the percentage of children in primary and secondary public schools with registered disabilities. Requirements governed by civil rights laws fundamentally change when comparing the support schools have to provide to students during primary and secondary school with disability access in postsecondary higher education. Psychiatrists may be asked to assist with scholastic disability at any stage of education and need to know about available supports and the parameters of disability in schools. Specifically, special attention should to be made in preparation for transition to postsecondary education when prior accommodations exist. PMID- 26806092 TI - The Likelihood of Recent Record Warmth. AB - 2014 was nominally the warmest year on record for both the globe and northern hemisphere based on historical records spanning the past one and a half centuries. It was the latest in a recent run of record temperatures spanning the past decade and a half. Press accounts reported odds as low as one-in-650 million that the observed run of global temperature records would be expected to occur in the absence of human-caused global warming. Press reports notwithstanding, the question of how likely observed temperature records may have have been both with and without human influence is interesting in its own right. Here we attempt to address that question using a semi-empirical approach that combines the latest (CMIP5) climate model simulations with observations of global and hemispheric mean temperature. We find that individual record years and the observed runs of record-setting temperatures were extremely unlikely to have occurred in the absence of human-caused climate change, though not nearly as unlikely as press reports have suggested. These same record temperatures were, by contrast, quite likely to have occurred in the presence of anthropogenic climate forcing. PMID- 26806093 TI - Molybdenum induces pancreatic beta-cell dysfunction and apoptosis via interdependent of JNK and AMPK activation-regulated mitochondria-dependent and ER stress-triggered pathways. AB - Molybdenum (Mo), a well-known toxic environmental and industrial pollutant, causes adverse health effects and diseases in humans and has received attention as a potential risk factor for DM. However, the roles of Mo in the mechanisms of the toxicological effects in pancreatic beta-cells are mostly unclear. In this study, the results revealed dysfunction of insulin secretion and apoptosis in the pancreatic beta-cell-derived RIN-m5F cells and the isolated mouse islets in response to Mo. These effects were accompanied by a mitochondria-dependent apoptotic signals including a decreased in the MMP, an increase in cytochrome c release, and the activation of caspase cascades and PARP. In addition, ER stress was triggered as indicated by several key molecules of the UPR. Furthermore, exposure to Mo induced the activation of ERK1/2, JNK, AMPKalpha, and GSK3 alpha/beta. Pretreatment with specific pharmacological inhibitors (in RIN-m5F cells and isolated mouse islets) of JNK (SP600125) and AMPK (Compound C) or transfection with si-RNAs (in RIN-m5F cells) specific to JNK and AMPKalpha effectively prevented the Mo-induced apoptosis and related signals, but inhibitors of ERK1/2 and GSK3-alpha/beta (PD98059 and LiCl, respectively) did not reverse the Mo-induced effects. Additionally, both the inhibitors and specific si RNAs could suppress the Mo-induced phosphorylation of JNK and AMPKalpha each other. Taken together, these results suggest that Mo exerts its cytotoxicity on pancreatic beta-cells by inducing dysfunction and apoptosis via interdependent JNK and AMPK activation downstream-regulated mitochondrial-dependent and ER stress-triggered apoptosis pathways. PMID- 26806095 TI - Inner ear morphology of the cioclovina early modern European calvaria from Romania. AB - OBJECTIVES: The morphology of the human bony labyrinth is thought to preserve a strong phylogenetic signal and to be minimally, if at all, affected by postnatal processes. The form of the semicircular canals is considered a derived feature of Neanderthals and different from the modern human anatomy. Among other hominins, European Middle Pleistocene humans have been found to be most similar to Neanderthals. Early modern humans have been proposed to show a pattern that is distinct, but most similar to that of Holocene people. Here we examine the inner ear structures of the Cioclovina calvaria, one of the earliest reliably dated and relatively complete modern human crania from Europe, in the context of recent and fossil human variation. MATERIALS AND METHODS: Bony labyrinths were virtually extracted from CT scans of recent Europeans and Cioclovina. Using univariate and multivariate methods, measurements of the semicircular canals were compared with published measurements of other fossil specimens. RESULTS: Our results show that Cioclovina's inner ear morphology falls within the range of modern variation, with affinities to both Late Pleistocene modern humans and recent Europeans. Using discriminant functions, the sex of the Cioclovina specimen is estimated as male. DISCUSSION: Results agree with previous work showing that Cioclovina exhibits fully modern cranial morphology. PMID- 26806094 TI - Role of NLRC5 in progression and reversal of hepatic fibrosis. AB - BACKGROUND: NLRC5, as the largest member of NLRs family, has recently been identified as a critical regulator of immune responses through negatively regulating NF-kappaB which is associated with the development of hepatic fibrosis. However, the expression and potential roles of NLRC5 in hepatic fibrosis and its reversal are still to be defined. METHODS: C57BL/6 mice were treatment with carbon tetrachloride (CCl4) induce hepatic fibrosis and its reversal. In vitro, models of hepatic fibrosis and its reversal are established by the treatment with TGF-beta and MDI. The expression of NLRC5 was determined by RT-PCR, Western blot and immunohistochemistry. Consequently, NLRC5 was overexpressed or knockdown by transfecting PEGFP-C2-NLRC5 or NLRC5-siRNA respectively in the reversal of hepatic fibrosis, and the expression of fibrogenic genes such as alpha-SMA and Col1alpha1 was quantified. The NF-kappaB activity was detected as well. RESULTS: Immunohistochemistry, RT-PCR and Western blot analysis with liver tissues and primary HSCs showed that NLRC5 was highly expressed in hepatic fibrosis and correspondingly decreased in the reversal stage. The differential expression of NLRC5 was confirmed in vitro. Enforced NLRC5 expression increased the expression of alpha-SMA and Col1alpha1, and blockade of NLRC5 reduced the fibrotic response. While the opposite expression of phosphorylated NF-kB p65 and phospho-IkappaBalpha was found. CONCLUSION: NLRC5 is differentially expressed in hepatic tissues and hepatic stellate cells during hepatic fibrosis and its reversal. All the data indicated that NLRC5 may play a crucial role in regulating the reversal of hepatic fibrosis through NF-kappaB signaling pathway. PMID- 26806096 TI - pH monitoring of gastro-oesophageal reflux before and after laparoscopic sleeve gastrectomy. AB - BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a common obesity-related co-morbidity that is assessed objectively by 24-h pH monitoring. Some concerns have been raised regarding the risk of de novo GORD or exacerbation of pre existing GORD after laparoscopic sleeve gastrectomy. Here, 24-h pH monitoring was used to assess the influence of laparoscopic sleeve gastrectomy on postoperative GORD in obese patients with or without preoperative GORD. METHODS: From July 2012 to September 2014, all patients scheduled for laparoscopic sleeve gastrectomy were invited to participate in a prospective follow-up. Patients who underwent preoperative 24-h pH monitoring were asked to repeat the examination 6 months after operation. GORD was defined as an oesophageal pH < 4 for at least 4.2 per cent of the total time recorded. RESULTS: Of 89 patients, 76 had preoperative pH monitoring for GORD evaluation and 50 had postoperative reassessment. Patients without (group 1, 29 patients) or with (group 2, 21 patients) preoperative GORD were similar regarding age, sex ratio and body mass index. In group 1, the median (i.q.r.) total time at pH < 4 was significantly higher after surgery than before: 5.6 (2.5-9.5) versus 1.6 (0.7-2.9) per cent (P < 0.001). Twenty of the 29 patients experienced de novo GORD as determined by 24-h pH monitoring (P < 0.001). In group 2, total time at pH < 4 after surgery was no different from the preoperative value: 5.9 (3.9-10.7) versus 7.7 (5.2-10.3) per cent (P = 0.296). CONCLUSION: Laparoscopic sleeve gastrectomy was associated with de novo GORD in over two-thirds of patients, but did not seem to exacerbate existing GORD. PMID- 26806097 TI - Search for the missing lncs: gene regulatory networks in neural crest development and long non-coding RNA biomarkers of Hirschsprung's disease. AB - Hirschsprung's disease (HSCR), a birth defect characterized by variable aganglionosis of the gut, affects about 1 in 5000 births and is a consequence of abnormal development of neural crest cells, from which enteric ganglia derive. In the companion article in this issue (Shen et al., Neurogasterenterol Motil 28: 266-73), the authors search for long non-coding RNAs (lncRNAs) differentially expressed in bowel tissues of infants with HSCR. Microarray analysis of over 37 000 lncRNAs and 34 000 mRNAs was done. The key result was identification of a set of 5 lncRNAs that is a potential diagnostic biomarker of HSCR. In this minireview, I provide an overview of neural crest development and the gene regulatory networks involved in specification, epithelial-mesenchymal transition, and migration of neural crest cells. Genes involved in later development, proliferation, and differentiation of neural crest cells as they migrate into the gut are also reviewed. Many of these genes are associated with HSCR, including RET, GDNF, GFRalpha, EDN3, and EDNRB. LncRNAs and their roles in development and disease and their use as biomarkers are discussed. The authors of the companion article previously used a multipronged approach to elucidate the etiology of HSCR by examining the effects of specific miRNAs or lncRNAs and target genes on cell migration, proliferation, cell cycle, and apoptosis in vitro. These studies are discussed in terms of their elegance and limitations. The companion article identifies many new lncRNAs that, in addition to providing potential biomarkers of HSCR, may be a treasure trove for future investigations. PMID- 26806098 TI - Corrigendum. PMID- 26806099 TI - Mycobacterium Lysine epsilon-aminotransferase is a novel alarmone metabolism related persister gene via dysregulating the intracellular amino acid level. AB - Bacterial persisters, usually slow-growing, non-replicating cells highly tolerant to antibiotics, play a crucial role contributing to the recalcitrance of chronic infections and treatment failure. Understanding the molecular mechanism of persister cells formation and maintenance would obviously inspire the discovery of new antibiotics. The significant upregulation of Mycobacterium tuberculosis Rv3290c, a highly conserved mycobacterial lysine epsilon-aminotransferase (LAT) during hypoxia persistent model, suggested a role of LAT in persistence. To test this, a lat deleted Mycobacterium smegmatis was constructed. The expression of transcriptional regulator leucine-responsive regulatory protein (LrpA) and the amino acids abundance in M. smegmatis lat deletion mutants were lowered. Thus, the persistence capacity of the deletion mutant was impaired upon norfloxacin exposure under nutrient starvation. In summary, our study firstly reported the involvement of mycobacterium LAT in persister formation, and possibly through altering the intracellular amino acid metabolism balance. PMID- 26806101 TI - Epidemiology, risk factor, species distribution, antifungal resistance and outcome of Candidemia at a single French hospital: a 7-year study. AB - Candidemia remains a major cause of disease worldwide and is associated with a high mortality rate. We conducted a retrospective study of candidemia at Nantes Hospital, France, between 2004 and 2010. A total of 191 episodes (n = 188 patients) were reviewed. Incidence, demographics, risk factors, antifungal management, species identification, in vitro susceptibility and 12 weeks survival were analysed. Global incidence of candidemia was 0.370/00 admissions. Higher incidences were observed in haematology (6.650/00) and intensive care units (20/00). Central venous catheter and antibiotic exposure were the most frequent risk factors (77% and 76% respectively). Candida albicans was the predominant species (51.8%) followed by C. parapsilosis (14.5%), C. glabrata (9.8%), C. tropicalis (9.8%) and C. krusei (4.1%). However, species distribution differed significantly between medical units with frequency of C. tropicalis being higher in haematology compared to other medical units. Fluconazole and caspofungin were the main antifungals given as first-line therapy. Although not significant, 12 weeks mortality rate was 30.9%, being higher for C. tropicalis (44.4%) than for C. parapsilosis (16%). Acquired azole or echinocandin resistance was noted in some isolates, underlining the need for systematic antifungal susceptibility testing in patients with candidemia. These epidemiological findings will be of interest for antifungal stewardship at our hospital. PMID- 26806100 TI - Evaluation of [11C]TAZA for amyloid beta plaque imaging in postmortem human Alzheimer's disease brain region and whole body distribution in rodent PET/CT. AB - OBJECTIVE: Alzheimer's disease (AD) is a neurodegenerative disease characterized by Abeta plaques in the brain. The aim of this study was to evaluate the effectiveness of a novel radiotracer, 4-[(11) C]methylamino-4'-N,N dimethylaminoazobenzene ([(11)C]TAZA), for binding to Abeta plaques in postmortem human brain (AD and normal control (NC)). METHODS: Radiosyntheses of [(11)C]TAZA, related [(11)C]Dalene ((11)C-methylamino-4'-dimethylaminostyrylbenzene), and reference [(11)C]PIB were carried out using [(11)C]methyltriflate prepared from [(11) C]CO(2) and purified using HPLC. In vitro binding affinities were carried out in human AD brain homogenate with Abeta plaques labeled with [(3) H]PIB. In vitro autoradiography studies with the three radiotracers were performed on hippocampus of AD and NC brains. PET/CT studies were carried out in normal rats to study brain and whole body distribution. RESULTS: The three radiotracers were produced in high radiochemical yields (>40%) and had specific activities >37 GBq/MUmol. TAZA had an affinity, K(i) = 0.84 nM and was five times more potent than PIB. [(11)C]TAZA bound specifically to Abeta plaques present in AD brains with gray matter to white matter ratios >20. [(11)C]TAZA was displaced by PIB (>90%), suggesting similar binding site for [(11)C]TAZA and [(11)C]PIB. [(11)C]TAZA exhibited slow kinetics of uptake in the rat brain and whole body images showed uptake in interscapular brown adipose tissue (IBAT). Binding in brain and IBAT were affected by preinjection of atomoxetine, a norepinephrine transporter blocker. CONCLUSION: [(11)C]TAZA exhibited high binding to Abeta plaques in human AD hippocampus. Rat brain kinetics was slow and peripheral binding to IBAT needs to be further evaluated. PMID- 26806103 TI - Direct Synthesis of Multicolor Fluorescent Hollow Carbon Spheres Encapsulating Enriched Carbon Dots. AB - Multicolor fluorescent hollow carbon spheres (HCSs) are fabricated by an easy one step route of in situ pyrolysis process with the use of natural scales and collagen powders as the precursor. The gas blow forming mechanism and photoluminescence (PL) emission mechanism of HCSs have been thoroughly discussed and proved that HCSs represent the first examples of three-dimensional multicolor fluorescent nanomaterials based on carbon dots (CDs). The HCSs encapsulate enriched carbon dots with high quantum yields (QYs) of 38%, and thus are applied in inkjet printing and sensitized solar cells. This strategy offers a promising avenue for preparing multicolor fluorescent hollow carbon materials on an industrial scale. PMID- 26806104 TI - Evaporation-induced Self-assembly Process Controlled for Obtaining Highly Ordered Mesoporous Materials with Demanded Morphologies. AB - A large number of periodic mesoporous materials have been reported using amphiphilic organic molecules with increasing development of synthetic methods for mesostructural, morphological, and compositional designs. The evaporation induced self-assembly (ESIA) process to fabricate ordered mesoporous films is one of the most essential synthetic methods, which has extensively been applied for obtaining a wide variety of samples (e.g., films and monoliths, including powders). It contains complicated physical variations and chemical reactions, but has been simply explained by several research groups. However, a current, exact understanding of such complicated systems should be given with respect to all the variations and reactions. In this article, I have mainly surveyed the exact EISA process by considering the difference between simple and controlled EISA processes on the basis of my own experiments. I believe that the insights are consequently helpful for obtaining highly ordered mesoporous materials with demanded morphologies. PMID- 26806106 TI - Mechanical Reversibility of Strain-Promoted Azide-Alkyne Cycloaddition Reactions. AB - Mechanophores, that is, molecules that show a defined response to force, are crucial building blocks of mechanoresponsive materials. The possibility of mechanically induced cycloreversion for a series of triazoles formed via strain promoted azide-alkyne cycloaddition reactions was investigated by density functional theory calculations, and these triazoles were compared to the 1,4- and 1,5-regioisomers formed in the reaction of an azide with a terminal alkyne. We show that cycloreversion is in principal possible and that the pulling geometry is the most important parameter that determines the probability of cycloreversion. We further compared triazole stability to the mechanical stability of polymers that are frequently used as force transducers in mechanochemical experiments and identified DIBAC (azadibenzylcyclooctyne) as a promising mechanophore for future applications. PMID- 26806107 TI - Pathogenic mutation R959W alters recognition dynamics of dysferlin inner DysF domain. AB - Dysferlin, a 220 kD protein, plays a major role in regulating plasma membrane repair in muscle cells. Mutations in the dysferlin inner DysF domain are known to cause different types of muscular dystrophy, including limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM). Replacement of arginine in position 959 by tryptophan has been frequently associated with both LGMD2B and MM, but the molecular mechanisms by which this mutation alters dysferlin function remain unknown. In this study, we have used protein binding site predictions and microsecond molecular dynamics (MD) simulations to determine the effects pathogenic mutation R959W on the structural dynamics of dysferlin inner DysF domain. Analysis of 2 MUs long MD trajectories revealed that mutation R959W does not induce local destabilization, unfolding or misfolding of the domain. We used a binding site predictor to discover a protein-binding site (residues T958-I966 and E1031-H1037) that resembles pincers in shape. Cartesian principal component analysis and interresidue distance distributions of the wild-type domain showed that the predicted protein-binding site undergoes a pincer motion, and populates two structural states, open and closed. We found that mutation R959W inhibits the pincer motion of the protein-binding site and completely shifts the equilibrium toward the open state. These differences in the structural dynamics of the predicted binding site suggest that mutation R959W alters recognition dynamics of the inner DysF domain. Based on these findings and on previous experimental studies, we propose a novel role for the inner DysF domain in muscle membrane repair through recruitment of dysferlin to plasma membrane. In conclusion, these findings have important implications for our understanding of the structural aspects of muscular dystrophies in atomic-level resolution. PMID- 26806111 TI - Trans-Omics: How To Reconstruct Biochemical Networks Across Multiple 'Omic' Layers. AB - We propose 'trans-omic' analysis for reconstructing global biochemical networks across multiple omic layers by use of both multi-omic measurements and computational data integration. We introduce technologies for connecting multi omic data based on prior knowledge of biochemical interactions and characterize a biochemical trans-omic network by concepts of a static and dynamic nature. We introduce case studies of metabolism-centric trans-omic studies to show how to reconstruct a biochemical trans-omic network by connecting multi-omic data and how to analyze it in terms of the static and dynamic nature. We propose a trans ome-wide association study (trans-OWAS) connecting phenotypes with trans-omic networks that reflect both genetic and environmental factors, which can characterize several complex lifestyle diseases as breakdowns in the trans-omic system. PMID- 26806112 TI - The Closure of the Cycle: Enzymatic Synthesis and Functionalization of Bio-Based Polyesters. AB - The polymer industry is under pressure to mitigate the environmental cost of petrol-based plastics. Biotechnologies contribute to the gradual replacement of petrol-based chemistry and the development of new renewable products, leading to the closure of carbon circle. An array of bio-based building blocks is already available on an industrial scale and is boosting the development of new generations of sustainable and functionally competitive polymers, such as polylactic acid (PLA). Biocatalysts add higher value to bio-based polymers by catalyzing not only their selective modification, but also their synthesis under mild and controlled conditions. The ultimate aim is the introduction of chemical functionalities on the surface of the polymer while retaining its bulk properties, thus enlarging the spectrum of advanced applications. PMID- 26806114 TI - Late rectal toxicity determined by dose-volume parameters in computed tomography based brachytherapy for locally advanced cervical cancer. AB - The aim of this study was to observe the relationship between dose-volume histogram (DVH) parameters and rectal late side effects (LSE) in computed tomography (CT)-based brachytherapy (BT) for patients with locally advanced cervical cancer. In total, 144 cervical cancer patients received external beam radiotherapy and CT-based BT. The data from 111 survival cases with pelvic local control (LC) were used to analyze the relationship between DVH parameters and rectal LSE. The total doses, manifesting 2, 1, and 0.1 cm(3) (D2cc , D1cc , and D0.1cc ) of the rectum, and D90 for high-risk clinical target volume (HR CTV) were computed and normalized to 2 Gy fractions (EQD2) using a linear-quadratic model. The rectal LSE were evaluated by the late effects in normal tissues subjective, objective, management, and analytic (LENT-SOMA) scale. A dose response relationship was evaluated by probit analyses. For all patients, the total rate of rectal LSE was 56%, and the rate of >=Grade 2 LSE was 27.4%. For the 111 survival cases with pelvic LC, the total mean for D2cc was 71.23 +/- 5.54 Gy for the rectum, and the D2cc , D1cc , and D0.1cc values for Grades 2 and 3 were higher than those for Grades 0 and 1. In addition, the number of complications increased, and the complications became more severe as the dose increased, with a dose of 73.5 Gy resulting in a 10% probability of >=Grade 3 LSE. In conclusion, DVH parameters could predict the incidence and grades of rectal LSE in CT-based BT. D2cc showed an excellent predictive value, and 73.5 Gy for D2cc of the rectum might be considered as an alternative dose limit. PMID- 26806115 TI - New Potent SARS-CoV 3C-Like Protease Inhibitors Derived from Thieno[2,3-d] pyrimidine Derivatives. AB - 2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (1) condensed with carbaldehydes 2a,b to give the respective thienopyrimidines (3a,b), which reacted with phosphoryl chloride and hydrazine hydrate to afford the respective pyrimidinohydrazines (4a,b). Compound 4a condensed with acetophenone under Vilsmeier conditions to afford the formylated pyrazolopyrimidine 6. Condensation of 4a with active methylenes produced the respective pyrazolopyrimidines (7-11). Besides, 4a condensed with succinic anhydride and with phthalic anhydride, yielding the pyrrolidine-2,5-dione 12 and the isoindoline-1,3-dione 13, respectively. Moreover, 4a reacted with isatin to afford the hydrazono-indolin-2 one 14. Structural elucidations for the new thienopyrimidines were based upon compatible analytical and spectroscopic results. Eleven of the new compounds were tested and found active against influenza A neuraminidase virus (H3N2). Compounds 12 and 13 were the most potent. PMID- 26806116 TI - Rectangular Co3O4 with micro-/nanoarchitectures: charge-driven PDDA-assisted synthesis and excellent lithium storage performance. AB - For the first time, two dimensional (2D) rectangular Co3O4 with micro /nanoarchitectures is successfully synthesized by a facile hydrothermal treatment with the assistance of poly(diallyldimethylammonium chloride) (PDDA). Owing to the strong electrostatic interaction, positively charged PDDA molecules are considered as structure directing agents and play a crucial role in the formation of the unique 2D rectangular structure. Material characterization suggests that rectangular Co3O4 is typically endowed with a side length of 3-5 MUm and a thickness of around 85 nm, and is composed of numerous interconnected nanocrystals about 15 nm in size. The interconnected nanocrystals provide few trap numbers for the electron transport process and contribute to the mesoporous structure with an average pore size of 18 nm. Thus, the distinctive micro /nanoarchitectures effectively address the formidable challenges of Co3O4-based anode materials, highly favourable for enhancing lithium ion diffusion, improving electron transport pathways and alleviating volume variation during charge discharge processes. When rectangular Co3O4 (FST-1) is evaluated as anode material for lithium ion batteries, a high reversible capacity of 1076.9 mA h g( 1) and an excellent first cycle Coulombic efficiency of 88.6% are achieved at a current density of 500 mA g(-1), thus delivering a capacity retention of nearly 100% after 100 cycles. Moreover, when tested at current densities as high as 1000 mA g(-1) and 2000 mA g(-1) for 100 cycles, lithium storage capacities can still be retained at 1020.2 mA h g(-1) and 616.4 mA h g(-1), respectively. Interestingly, by simply varying the reaction conditions or types of positively charged polymers, the polyelectrolyte-assisted hydrothermal route can be successfully extended to synthesize other novel micro-/nanoarchitectures, such as straw-tied-like and urchin-like structures, demonstrating great potential in developing next-generation anode materials for high performance lithium ion batteries. PMID- 26806113 TI - 4R- and 4S-iodophenyl hydroxyproline, 4R-pentynoyl hydroxyproline, and S propargyl-4-thiolphenylalanine: conformationally biased and tunable amino acids for bioorthogonal reactions. AB - Bioorthogonal reactions allow the introduction of new functionalities into peptides, proteins, and other biological molecules. The most readily accessible amino acids for bioorthogonal reactions have modest conformational preferences or bases for molecular interactions. Herein we describe the synthesis of 4 novel amino acids containing functional groups for bioorthogonal reactions. (2S,4R)- and (2S,4S)-iodophenyl ethers of hydroxyproline are capable of modification via rapid, specific Suzuki and Sonogashira reactions in water. The synthesis of these amino acids, as Boc-, Fmoc- and free amino acids, was achieved through succinct sequences. These amino acids exhibit well-defined conformational preferences, with the 4S-iodophenyl hydroxyproline crystallographically exhibiting beta-turn (phi, psi~-80 degrees , 0 degrees ) or relatively extended (phi, psi~-80 degrees , +170 degrees ) conformations, while the 4R-diastereomer prefers a more compact conformation (phi~-60 degrees ). The aryloxyproline diastereomers present the aryl groups in a highly divergent manner, suggesting their stereospecific use in molecular design, medicinal chemistry, and catalysis. Thus, the 4R- and 4S iodophenyl hydroxyprolines can be differentially applied in distinct structural contexts. The pentynoate ester of 4R-hydroxyproline introduces an alkyne functional group within an amino acid that prefers compact conformations. The propargyl thioether of 4-thiolphenylalanine was synthesized via copper-mediated cross-coupling reaction of thioacetic acid with protected 4-iodophenylalanine, followed by thiolysis and alkylation. This amino acid combines an alkyne functional group with an aromatic amino acid and the ability to tune aromatic and side chain properties via sulfur oxidation. These amino acids provide novel loci for peptide functionalization, with greater control of conformation possible than with other amino acids containing these functional groups. PMID- 26806118 TI - Cholangiocarcinoma--current classification and challenges towards personalised medicine. PMID- 26806119 TI - Frank vectorcardiographic system from standard 12 lead ECG: An effort to enhance cardiovascular diagnosis. AB - BACKGROUND: Vectorcardiogram (VCG) has been repeatedly found useful for clinical investigations. It may not substitute but complement Standard 12-Lead (S12) ECG. There was tremendous research between 1950s to mid-1980s on VCG in general and Frank's System in particular, however, in last three decades it has been dropped as a routine cardiac test, the major reasons being unconventional electrode placements which required training of the physicians, greater number of electrodes involved when used to supplement S12 system and additional hardware complexity involved, at least in the early days. Although it lost the interest of cardiologists, the engineering community has adopted the VCG as a tool for interdisciplinary research. We envisage that, if accurate Frank's VCG system is made available avoiding the aforementioned limitations, VCG will complement S12 system in diagnosis of cardiovascular diseases (CVDs). METHODS AND RESULTS: In this paper, we propose a methodology to construct Frank VCG from S12 system using Principal Component Analysis (PCA). We have compared our work with state-of-the art Inverse Dower Transform (IDT) and Kors Transform (KT). Mean R(2) statistics and correlation coefficient values, obtained upon comparison of reconstructed and originally measured Frank's leads, for CSE multilead (CSEDB) and PhysioNet's PTBDB databases using our proposed method, IDT and KT were found to be (73.7%,0.869), (57.6%,0.788) and (56.2%,0.781) respectively. From remote healthcare perspective, a reduced 2-3 lead system is desired and Frank lead system seems to be promising as shown by previous works. However, cardiologists are accustomed to S12 system due to its widespread usage and derived Frank lead system might not be sufficient. Hence, to bridge the gap, we have presented the results of personalized reconstruction of S12 system from derived VCG, obtained using proposed PCA-based method and compared it with results obtained when originally measured Frank leads were used. CONCLUSIONS: The proposed methodology, without any modification in the current acquisition system, can be used to obtain Frank VCG from S12 system to complement it in CVD diagnosis. Omnipresent computerized machines can readily apply the proposed methodology and thus, can find widespread clinical application. PMID- 26806122 TI - Functional neuroimaging and diagnostic reasoning. PMID- 26806120 TI - Catheter ablation of atrial fibrillation in patients with concomitant sinus bradycardia-Insights from the German Ablation Registry. AB - AIMS: This investigation addresses procedural characteristics of catheter ablation in patients with atrial fibrillation (AF) and sinus bradycardia. METHODS: From the prospective, multi-center German Ablation Registry 1073 patients with sinus rhythm at the time of AF ablation were divided into two groups according to heart rate at start of procedure (A, <60 beats per minute (bpm), n=197; B, 60-99bpm, n=876). RESULTS: Acute procedural success was high (>=98%) and similar between groups. Procedure duration and energy application time were increased in group A (180min vs. 155min and 2561s vs. 1879s, respectively). Major complications were more frequent in group A (2.2% vs. 0.5%), and a greater proportion of these patients was discharged under antiarrhythmic medication (64% vs. 52%). CONCLUSION: Catheter ablation of AF with concomitant sinus bradycardia is associated with high procedural efficacy, longer procedure- and energy application durations, and a slightly elevated complication rate. PMID- 26806123 TI - Developmental trajectories of body mass index and emotional-behavioral functioning of underweight children: A longitudinal study. AB - Although several studies have addressed developmental trajectories from childhood to adolescence of internalizing/externalizing problems, limited attention has been given to underweight children. Two groups were recruited for this study from a community sample: underweight (Ug, N = 80, 50% female) and normal weight (NWg, N = 80, 50% female) to examine the developmental trajectories of body mass index and emotional-behavioral functioning of underweight children from the age two years, and their risk of eating disorder at early adolescence. The study was organized over four waves, each of three years. Pediatricians measured BMI, parents completed the Child Behavior Checklist (CBCL) and the Eating Disorders Inventory-Referral Form (EDI-3-RF). Our results showed that children in the two groups recorded different BMI trajectories over time. In NWg, male and female subjects started from a higher BMI at T1 than their peers. In Ug, internalizing and externalizing problems in males and females remained higher than their peers at all points of assessment. Males and females in Ug scored higher than those in NWg on EDI-3-RF total score. Our results indicate a need for effective physical and psychological assessment of underweight children in community samples to prevent psychological difficulties and eating disorders in adolescence. PMID- 26806124 TI - Systematic review with meta-analysis: coffee consumption and the risk of cirrhosis. AB - BACKGROUND: Liver cirrhosis is a large burden on global health, causing over one million deaths per year. Observational studies have reported an inverse association between coffee and cirrhosis. AIMS: To perform a systematic review and meta-analysis to characterise the relationship between coffee consumption and cirrhosis. METHODS: We searched for studies published until July 2015 that reported odds ratios, relative risks (RR) or hazard ratios for cirrhosis stratified by coffee consumption. We calculated RRs of cirrhosis for an increase in daily coffee consumption of two cups for each study and overall. We performed analyses by study design, type of cirrhosis and mortality. We assessed the risk of bias in each study and the overall quality of evidence for the effect of coffee on cirrhosis. RESULTS: We identified five cohort studies and four case control studies involving 1990 cases and 432 133 participants. We observed a dose response in most studies and overall. The pooled RR of cirrhosis for a daily increase in coffee consumption of two cups was 0.56 (95% CI 0.44-0.68; I(2) 83.3%). The RR pooled from cohort studies for a daily increase of two cups was 0.58 (95% CI 0.41-0.76; I(2) 91.1%) and from case-control studies it was 0.52 (95% CI 0.40-0.63; I(2) 0.0%). The pooled RR of alcoholic cirrhosis for a daily increase of two cups was 0.62 (95% CI 0.51-0.73; I(2) 0%) and of death from cirrhosis it was 0.55 (95% CI 0.35-0.74; I(2) 90.3%). CONCLUSION: This meta analysis suggests that increasing coffee consumption may substantially reduce the risk of cirrhosis. PMID- 26806126 TI - Long-term Outcome of Daylight Photodynamic Therapy with Amino-5-laevulinate Nanoemulsion vs. Methyl-5-aminolaevulinate for Actinic Keratoses. PMID- 26806127 TI - De Novo Evolutionary Emergence of a Symmetrical Protein Is Shaped by Folding Constraints. AB - Molecular evolution has focused on the divergence of molecular functions, yet we know little about how structurally distinct protein folds emerge de novo. We characterized the evolutionary trajectories and selection forces underlying emergence of beta-propeller proteins, a globular and symmetric fold group with diverse functions. The identification of short propeller-like motifs (<50 amino acids) in natural genomes indicated that they expanded via tandem duplications to form extant propellers. We phylogenetically reconstructed 47-residue ancestral motifs that form five-bladed lectin propellers via oligomeric assembly. We demonstrate a functional trajectory of tandem duplications of these motifs leading to monomeric lectins. Foldability, i.e., higher efficiency of folding, was the main parameter leading to improved functionality along the entire evolutionary trajectory. However, folding constraints changed along the trajectory: initially, conflicts between monomer folding and oligomer assembly dominated, whereas subsequently, upon tandem duplication, tradeoffs between monomer stability and foldability took precedence. PMID- 26806128 TI - Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection. AB - Recent studies have suggested that antibody-mediated protection against the Ebolaviruses may be achievable, but little is known about whether or not antibodies can confer cross-reactive protection against viruses belonging to diverse Ebolavirus species, such as Ebola virus (EBOV), Sudan virus (SUDV), and Bundibugyo virus (BDBV). We isolated a large panel of human monoclonal antibodies (mAbs) against BDBV glycoprotein (GP) using peripheral blood B cells from survivors of the 2007 BDBV outbreak in Uganda. We determined that a large proportion of mAbs with potent neutralizing activity against BDBV bind to the glycan cap and recognize diverse epitopes within this major antigenic site. We identified several glycan cap-specific mAbs that neutralized multiple ebolaviruses, including SUDV, and a cross-reactive mAb that completely protected guinea pigs from the lethal challenge with heterologous EBOV. Our results provide a roadmap to develop a single antibody-based treatment effective against multiple Ebolavirus infections. PMID- 26806129 TI - Mutational Strand Asymmetries in Cancer Genomes Reveal Mechanisms of DNA Damage and Repair. AB - Mutational processes constantly shape the somatic genome, leading to immunity, aging, cancer, and other diseases. When cancer is the outcome, we are afforded a glimpse into these processes by the clonal expansion of the malignant cell. Here, we characterize a less explored layer of the mutational landscape of cancer: mutational asymmetries between the two DNA strands. Analyzing whole-genome sequences of 590 tumors from 14 different cancer types, we reveal widespread asymmetries across mutagenic processes, with transcriptional ("T-class") asymmetry dominating UV-, smoking-, and liver-cancer-associated mutations and replicative ("R-class") asymmetry dominating POLE-, APOBEC-, and MSI-associated mutations. We report a striking phenomenon of transcription-coupled damage (TCD) on the non-transcribed DNA strand and provide evidence that APOBEC mutagenesis occurs on the lagging-strand template during DNA replication. As more genomes are sequenced, studying and classifying their asymmetries will illuminate the underlying biological mechanisms of DNA damage and repair. PMID- 26806130 TI - Cancer Immunosurveillance by Tissue-Resident Innate Lymphoid Cells and Innate like T Cells. AB - Malignancy can be suppressed by the immune system in a process termed immunosurveillance. However, to what extent immunosurveillance occurs in spontaneous cancers and the composition of participating cell types remains obscure. Here, we show that cell transformation triggers a tissue-resident lymphocyte response in oncogene-induced murine cancer models. Non-circulating cytotoxic lymphocytes, derived from innate, T cell receptor (TCR)alphabeta, and TCRgammadelta lineages, expand in early tumors. Characterized by high expression of NK1.1, CD49a, and CD103, these cells share a gene-expression signature distinct from those of conventional NK cells, T cells, and invariant NKT cells. Generation of these lymphocytes is dependent on the cytokine IL-15, but not the transcription factor Nfil3 that is required for the differentiation of tumor infiltrating NK cells, and IL-15 deficiency, but not Nfil3 deficiency, results in accelerated tumor growth. These findings reveal a tumor-elicited immunosurveillance mechanism that engages unconventional type-1-like innate lymphoid cells and type 1 innate-like T cells. PMID- 26806131 TI - Intrathecal Sufentanil Does Not Reduce Shivering During Neuraxial Anesthesia: A Meta-Analysis. AB - BACKGROUND: We performed this meta-analysis to evaluate the efficacy of intrathecal sufentanil in preventing shivering during neuraxial anesthesia. MATERIAL/METHODS: We searched the Cochrane Library, PubMed, and Embase for all randomized controlled trials (RCT) on use of intrathecal sufentanil for preventing shivering during neuraxial anesthesia. References of retrieved articles were also screened. The quality of the studies was evaluated by the method recommended by the Cochrane Collaboration. Meta-analysis was conducted using the Cochrane Collaboration's RevMan 5.3 software. The primary outcome was incidence and severity of shivering, and the secondary outcomes were drug-related complications of pruritus, nausea, vomiting, hypotension, and bradycardia. RESULTS: Eight original RCTs investigating a total of 1032 patients, of whom 599 received sufentanil and 473 received placebo, met the inclusion criteria. Compared to the placebo group, sufentanil did not reduce incidence of shivering (OR, 0.60; 95% CI, 0.35 to 1.01; P=0.06), but it increased the incidence of pruritus (OR, 12.52; 95% CI, 5.07 to 30.91; P<0.00001). Compared to the placebo group, sufentanil did not increase the incidence of nausea (OR, 0.69; 95% CI, 0.41 to 1.16; P=0.16), hypotension (OR, 0.93; 95% CI, 0.62 to 1.41; P=0.74), or bradycardia (OR, 0.86; 95% CI, 0.41 to 1.82; P=0.70). In addition, sufentanil reduced the incidence of vomiting during neuraxial anesthesia (OR, 0.45; 95% CI, 0.22 to 0.92; P=0.03). CONCLUSIONS: Neither epidural nor subarachnoid intrathecal sufentanil reduced shivering during neuraxial anesthesia, but it did increase the incidence of pruritus. PMID- 26806133 TI - The worldwide spread of ciprofloxacin-resistant Shigella sonnei among HIV infected men who have sex with men, Taiwan. AB - Ciprofloxacin-resistant shigellosis outbreaks among men who have sex with men (MSM) have not been reported in Asia. During 3 March to 6 May 2015, the Notifiable Disease Surveillance System detected nine non-imported Shigella sonnei infections among human immunodeficiency virus (HIV) -infected Taiwanese MSM. We conducted a molecular epidemiological investigation using a 1 : 5 matched case control study and laboratory characterizations for the isolates. Of the nine patients, four reported engagement in oral-anal sex before illness onset. Shigellosis was associated with a syphilis report within 12 months (adjusted odds ratio (aOR) 8.6; 95% CI 1.05-70.3) and no HIV outpatient follow-up within 12 months (aOR 22.3; 95% CI 2.5-201). Shigella sonnei isolates from the nine patients were all ciprofloxacin-resistant and the resistance was associated with S83L and D87G mutations in gyrA and S80I mutation in parC. The nine outbreak isolates were discriminated into two closely related pulsed-field gel electrophoresis (PFGE) genotypes and seven 8-locus multilocus variable-number tandem repeat analysis (MLVA8) types that suggest multiple sources of infections for the outbreak and possible under-recognition of infection among Taiwanese MSM. The outbreak isolates were characterized to be variants of the intercontinentally transmitted SS18.1 clone, which falls into the globally prevalent phylogenetic sub-lineage IIIb. Inter-database pattern similarity searching indicated that the two PFGE genotypes had emerged in the USA and Japan. The epidemiological characteristics of this outbreak suggest roles of risky sexual behaviours or networks in S. sonnei transmission. We urge enhanced surveillance and risk reduction interventions regionally against the interplay of HIV and shigellosis among MSM. PMID- 26806134 TI - Validation of a treatment algorithm for orthopaedic implant-related infections with device-retention-results from a prospective observational cohort study. AB - Success rates for treatment regimens involving retention of an infected implant are conflicting and failure rates of up to 80% have been reported. We aimed to validate a proposed treatment algorithm, based on strict selection criteria, by assessing long-term outcome of treatment for orthopaedic device-related infection (ODRI) with retention. From January 1999 to December 2009, all patients diagnosed with ODRI at the University Hospital Basel, Switzerland were eligible for treatment with open surgical debridement, implant-retention and antibiotics, if duration of clinical symptoms was <=3 weeks, the implant was stable, the soft tissue had no abscess or sinus tract, and the causative pathogen was susceptible to antimicrobial agents with activity against surface-adhering microorganisms. Antimicrobial treatment was administered according to a predefined algorithm. The primary outcome was treatment failure after 2-year follow up. A total of 455 patients were diagnosed with an ODRI, of whom 233 (51.2%) patients were eligible for treatment involving implant-retention. Causative pathogens were mainly Staphylococcus aureus (41.6%) and coagulase-negative staphylococci (33.9%). Among patients with ODRIs related to prostheses, failure was documented in 10.8% (12/111) and in patients with ODRIs related to osteosyntheses, failure occurred in 9.8% (12/122) after 2 years of follow up. In all, 90% of ODRIs were successfully cured with surgical debridement and implant-retention in addition to long-term antimicrobial therapy according to a predefined treatment algorithm: if patients fulfilled strict selection criteria and there was susceptibility to rifampin for Gram-positive pathogens and ciprofloxacin for Gram-negative pathogens. PMID- 26806135 TI - Laboratory automation in clinical bacteriology: what system to choose? AB - Automation was introduced many years ago in several diagnostic disciplines such as chemistry, haematology and molecular biology. The first laboratory automation system for clinical bacteriology was released in 2006, and it rapidly proved its value by increasing productivity, allowing a continuous increase in sample volumes despite limited budgets and personnel shortages. Today, two major manufacturers, BD Kiestra and Copan, are commercializing partial or complete laboratory automation systems for bacteriology. The laboratory automation systems are rapidly evolving to provide improved hardware and software solutions to optimize laboratory efficiency. However, the complex parameters of the laboratory and automation systems must be considered to determine the best system for each given laboratory. We address several topics on laboratory automation that may help clinical bacteriologists to understand the particularities and operative modalities of the different systems. We present (a) a comparison of the engineering and technical features of the various elements composing the two different automated systems currently available, (b) the system workflows of partial and complete laboratory automation, which define the basis for laboratory reorganization required to optimize system efficiency, (c) the concept of digital imaging and telebacteriology, (d) the connectivity of laboratory automation to the laboratory information system, (e) the general advantages and disadvantages as well as the expected impacts provided by laboratory automation and (f) the laboratory data required to conduct a workflow assessment to determine the best configuration of an automated system for the laboratory activities and specificities. PMID- 26806136 TI - Impact of PNPLA3 variants on liver histology of 168 patients with HIV infection and chronic hepatitis C. AB - This study analysed the impact of PNPLA3 variants on liver histology of 168 HIV/hepatitis C virus (HCV)-coinfected patients who were naive for HCV treatment. A athologist unaware of the patients' condition graded liver fibrosis and necroinflammation (Ishak) and steatosis (Kleiner). Patients were tested for PNPLA3 variants and genotyped for the PNPLA3 rs738409 C to G variant underlying the I148M substitution. All were hepatitis B surface antigen negative and stated no alcohol abuse. The mean age was 40.6 (37.6-44.1) years, 72.6% were males, 42% had HCV genotype 3, 38.9% HCV genotype 1 and 79.2% were receiving highly active antiretroviral therapy. The 79 patients with the PNPLA3 p.148I/M or M/M variants more frequently showed severe steatosis (score 3-4) than the 89 with PNPLA3 p.148I/I (43% vs. 24.7%, p 0.001), whereas no difference was observed in the degree of necroinflammation or fibrosis. Compared with 112 patients with lower scores, 56 with severe steatosis showed higher body mass index (p 0.03), higher rate of HCV genotype 3 (55.6% vs. 35.2%, p 0.01), PNPLA3 p.148I/M or M/M (60.7% vs. 39.3%, p 0.01) and lower CD4(+) cells/mm(3) (514.00 (390.5-673.0) vs. 500.00 (399.0-627.0); p 0.002). At multivariate analysis, body mass index (p 0.01), HCV genotype 3 (p 0.006), CD4(+) cell count (p 0.005) and PNPLA3 p.148I/M or M/M variants (p 0.01) were found to be independent predictors of severe liver steatosis. The PNPLA3 p.148 I/M or M/M variants and CD4(+) cell count were the only independent predictors of severe steatosis in patients with HCV non-3 genotypes. This is the first study to show that among HIV/HCV-coinfected patients the PNPLA3 p.148I/M or M/M variant have substantially less impact on steatosis for those with HCV genotype 3 than non-genotype 3. PMID- 26806137 TI - Healthcare-associated Crimean-Congo haemorrhagic fever in Turkey, 2002-2014: a multicentre retrospective cross-sectional study. AB - Healthcare-related transmission of Crimean-Congo haemorrhagic fever (CCHF) is a well-recognized hazard. We report a multicentre retrospective cross-sectional study undertaken in Turkey in 2014 in nine hospitals, regional reference centres for CCHF, covering the years 2002 to 2014 inclusive. Data were systematically extracted from charts of all personnel with a reported health care injury/accident related to CCHF. Blood samples were tested for CCHF IgM/IgG by enzyme-linked immunosorbent assay and/or viral nucleic acid detection by PCR after the injury. Fifty-one healthcare-related exposures were identified. Twenty five (49%) of 51 resulted in laboratory-confirmed infection, with a 16% (4/25) overall mortality. The main route of exposure was needlestick injury in 32/51 (62.7%). A potential benefit of post-exposure prophylaxis with ribavirin was identified. PMID- 26806138 TI - Treatment of complicated skin and skin structure infections in areas with low incidence of antibiotic resistance-a retrospective population based study from Finland and Sweden. AB - Complicated skin and skin-structure infections (cSSSI) are a common reason for hospitalization and practically all new antimicrobial agents against Gram positive bacteria are studied in cSSSI. The aim of this population-based observational study was to assess the treatment of patients with cSSSI in areas with a low incidence of antibiotic resistance. The study population consisted of adult residents who were treated because of cSSSI during 2008-2011 from two Nordic cities, Helsinki and Gothenburg. In the final analysis population (460 patients; mean age 60.8 years; 60.9% male) 13.3% of patients had bacteraemia, 15.9% were admitted to an Intensive Care Unit and 51.5% underwent at least one surgical intervention. Treatment failure occurred in 28.2%, initial antibiotic treatment modification to another intravenous drug in 38.5% and streamlining in 5.0% of the cases. Gram-positive bacteria were predominantly isolated, with staphylococci (24.5%) and streptococci (16.0%) being the most common aetiologies. Median overall durations of hospital stay and antimicrobial treatment were 13 and 17 days, respectively, and on average 3.5 (SD 2.1) different antibiotics were used per patient. Oral antimicrobial treatment was continued in 64.3% of patients after discharge. The overall mortality rates in 30 days and in 12 months were 4.1% and 11.8%, respectively, and 16.4% of patients had a recurrence of SSSI within 12 months. In conclusion, in this population-based study antimicrobial treatment modifications were frequent and the treatment time was longer than recommended. However, bacteraemia, clinical failure and recurrences were more common than in previous non-population-based studies. PMID- 26806139 TI - Mucormycosis in Australia: contemporary epidemiology and outcomes. AB - Mucormycosis is the second most common cause of invasive mould infection and causes disease in diverse hosts, including those who are immuno-competent. We conducted a multicentre retrospective study of proven and probable cases of mucormycosis diagnosed between 2004-2012 to determine the epidemiology and outcome determinants in Australia. Seventy-four cases were identified (63 proven, 11 probable). The majority (54.1%) were caused by Rhizopus spp. Patients who sustained trauma were more likely to have non-Rhizopus infections relative to patients without trauma (OR 9.0, p 0.001, 95% CI 2.1-42.8). Haematological malignancy (48.6%), chemotherapy (42.9%), corticosteroids (52.7%), diabetes mellitus (27%) and trauma (22.9%) were the most common co-morbidities or risk factors. Rheumatological/autoimmune disorders occurred in nine (12.1%) instances. Eight (10.8%) cases had no underlying co-morbidity and were more likely to have associated trauma (7/8; 87.5% versus 10/66; 15.2%; p <0.001). Disseminated infection was common (39.2%). Apophysomyces spp. and Saksenaea spp. caused infection in immuno-competent hosts, most frequently associated with trauma and affected sites other than lung and sinuses. The 180-day mortality was 56.7%. The strongest predictors of mortality were rheumatological/autoimmune disorder (OR = 24.0, p 0.038 95% CI 1.2-481.4), haematological malignancy (OR = 7.7, p 0.001, 95% CI 2.3-25.2) and admission to intensive care unit (OR = 4.2, p 0.02, 95% CI 1.3-13.8). Most deaths occurred within one month. Thereafter we observed divergence in survival between the haematological and non-haematological populations (p 0.006). The mortality of mucormycosis remains particularly high in the immuno-compromised host. Underlying rheumatological/autoimmune disorders are a previously under-appreciated risk for infection and poor outcome. PMID- 26806140 TI - [Pubertal maturation, physical self-esteem and sexuality in a sample of French adolescents]. AB - AIM: The aim of this study was to explore the links between pubertal maturation, physical self-esteem and sexuality in adolescence, differentiating between boys and girls. METHOD: The sample was comprised of 312 French secondary school children (seventh and ninth grades); 52.6 % (n=164) of whom were girls. Participants answered three self-evaluation questionnaires: the scale of sexuality (interests, emotions, relationships: IERS) in prime adolescence (12 to 15 years); (b) the self-administered rating scale for pubertal development and (c) the Physical Self-Description Questionnaire (PSDQ). RESULTS: Pubertal maturation was associated with higher scores on "Flirting with the aim of having sexual relations" and "Going out with someone", and a drop in overall and physical self-esteem, mainly in socially valued domains, namely "Body fat" for girls, and "Strength" and "Health" for boys. Overall physical self-esteem was associated with "Going out with someone" and "Flirting with the aim of having sexual relations" in boys. DISCUSSION: Physical changes at puberty induce two distinct trends in adolescents: sexual exploration and discovery (genitalized body), and self-depreciation (social body). PMID- 26806141 TI - [The assessment of spirituality and religiousness in patients with psychosis]. AB - OBJECTIVES: There is evidence that psychiatrists are rarely aware of how religion may intervene in their patient's life. That is particularly obvious concerning patients with psychosis. Yet, even for patients featuring delusions with religious content, religious activities and spiritual coping may have a favourable influence. Indeed, patients with psychosis can use religion to cope with life difficulties related to their psychotic condition, in a social perspective but also in order to gain meaning in their lives. Also, religion may be part of explanatory models about their disorder with, in some cases, a significant influence on treatment adhesion. PATIENTS AND METHODS: This paper describes a prospective randomized study about a spiritual assessment performed by the psychiatrists of patients with schizophrenia. The outpatient clinics in which the sample was collected are affiliated with the department of psychiatry at the university hospitals of Geneva. Eighty-four outpatients with psychosis were randomized into two groups: an experimental group receiving both traditional treatment and spiritual assessment with their psychiatrist and a control group of patients receiving only their usual treatment. Psychiatrists were supervised by a clinician (PH) and a psychologist of religions (PYB) for each patient in the spiritual assessment group. Data were collected from both groups before and after 3 months of clinical follow-up. RESULTS: Spiritual assessment was well-tolerated by all patients. Moreover, their wish to discuss religious matters with their psychiatrist persisted following the spiritual assessment. Even though clinicians acknowledged the usefulness of the supervision for some patients, especially when religion was of importance for clinical care, they reported being moderately interested in applying spiritual assessments in clinical settings. Compared to the control group, there were no differences observed in the 3 months' outcome in terms of primary outcome measures for satisfaction with care, yet the attendance at the appointments was significantly increased in the group with spiritual assessment. The same result was found when restricting analyses to patients for whom an intervention was suggested or patients who invested more in religion. Areas of potential intervention were frequent both in a psychiatric and psychotherapeutical perspective. CONCLUSIONS: Spiritual assessment appears to be useful for patients with psychosis. This is in accordance with the recommendations of the World Psychiatric Association which promotes considering the whole person in clinical care. Spiritual assessment is quite simple to perform, providing that clinicians do not prescribe or promote religion, and that no critical comments are made concerning religious issues. Clinicians do not need to know in depth the religious domains of each of their patients, as it appears that each patient accommodates his/her religious background his/her own way. PMID- 26806142 TI - [Burnout and psychosocial risk factors in the career of flight attendants: Descriptive study of a population of Lebanese flight attendants]. AB - OBJECTIVE: The aim of our study was to investigate the influence of demographic factors (gender and age), work related factors (the position and years of practice) and psychosocial risk factors (cognitive demands, demands to hide emotions, work-family conflict, offensive behaviors...) on the development of burnout among flight attendants, and the nature of psychosocial factors to which they are exposed. METHODS: The sample was divided into two groups: 67 flight attendants and 67 persons in various jobs. Our sampling units were informed and consented to fill in two questionnaires: the Copenhagen burnout inventory (CBI) and the Copenhagen Psychosocial Questionnaire (COPSOQ II). RESULTS: The burnout syndrome affected both groups equally. It affected equally the women as well as men, whatever their age categories and their years of experience. The flight attendants occupying an intermediate position in the hierarchy had the highest score on the burnout syndrome. The psychosocial factors significantly found in flight attendants compared to the control group were: demands for hiding emotions, quantitative demands, emotional demands, temporal demands, lack of influence at work, of rewards, of possibility for development and variation of work, poor quality of leadership, exposure to sexual harassment, lack of social support from supervisors, colleagues, social community at work and work-family conflict. Four of them correlated positively with the development of burnout: quantitative demands, temporal demands, emotional demands and work-family conflict. Their expected work volume is very high (quantitative demands). They have to perform their tasks quickly in a limited time without forgetting the technical constraints (temporal demands). They have to work with an average of three hundred passengers besides colleagues and subordinates, which requires diligent control of the emotions promoted by the airline code of conduct based on repression of emotions (emotional demands). These demands affect the workers once they find themselves in their family environment and can have a negative effect on their private life (work-family conflict). However, the predictability seems to allow them to be aware of decisions and changes and protect them against burnout. CONCLUSION: The profession of flight attendants appears to be characterized by some psychosocial risk factors, some of which are positively correlated with burnout. Improved working conditions can prevent these risks and protect these employees from burnout. PMID- 26806143 TI - [Suicide and evaluation. Review of French tools: Non-dimensional approach and self-assessment]. AB - Suicide prevention represents a major challenge to public health, and the suicide risk is a permanent concern in psychiatry. But the main difficulty is its diagnosis. What resources are available in French which seem to help therapists in this process? We can distinguish the non-dimensional approach, the use of self administered questionnaires or interviewer-administrated questionnaires. In this paper, for reasons of editing constraints, we are interested only in a non dimensional approach and direct assessment measures by self-assessment, analysing the strengths and limitations of each and taking into account scientific studies that have been devoted to them and their clinical relevance. We first considered various aspects of non-dimensional approach through suicidal risk factors research, suicidal emergency and suicidal potential concepts, Shea approach, the model of Mann and some recommended evaluations. This type of approach has a number of advantages, but also limitations. Dimensional approach allows going further. In this article, we also discuss the existing self-assessment tools in French as for example dedicated item for Beck Depression Inventory (BDI) or specific scales such as Reasons for Living Inventory (RFL), Suicidal Probability Scale (SPS), Beck Hopelessness Scale (BHS) and self-administered Suicide Risk Assessment Scale of Ducher (aRSD). These last two seem to be used as a priority regarding result of their validation studies. The strong correlation between the self-administered questionnaire aRSD and the interviewer-administered Suicide Risk Assessment Scale of Ducher RSD (r=0.92; P<10(-7)) shows the ability of patients to express their suicidal ideation if we want to invite them to do so. PMID- 26806144 TI - New insights into transfusion-related iron toxicity: Implications for the oncologist. AB - Iron overload is a potentially life-threatening consequence of multiple red-blood cell transfusions. Here, we review factors affecting excess iron distribution and its damage to specific tissues, as well as mechanisms of oncogenesis by iron. Although consequences of transfusional iron overload are best described in thalassemia major and related inherited anemias, they are increasingly recognized in acquired conditions, such as myelodysplastic syndromes (MDS). Iron overload in MDS not only impacts on certain tissues, but may affect the clonal evolution of MDS through generation of reactive oxygen species. Iron overload may also influence hematopoietic-stem-cell-transplantation outcomes. Novel MRI methods for assessing body iron have impacted significantly on outcome in inherited anemias by allowing monitoring of iron burden and iron chelation therapy. This approach is increasingly being used in MDS and stem-cell-transplant procedures. Knowledge gained from managing transfusional iron overload in inherited anemias may be translated to general oncology, with potential for improved patient outcomes. PMID- 26806145 TI - Opioid switching in cancer pain: From the beginning to nowadays. AB - Opioid switching is the process of changing from one opioid to another to obtain a satisfactory clinical balance between analgesia and adverse effects. This pharmacological technique has been introduced about 20 years ago to enhance the opioid response in advanced cancer patients with chronic pain. More information is now available. This review will examine many different aspects of opioid switching, including the history and evolution through the last decades, some clinical aspects based on the most recent experience, controversies on the indications, conversion ratios and modalities of switching in some specific circumstances, and evidence based recommendations. PMID- 26806146 TI - Immunomodulatory drugs in AL amyloidosis. AB - Immunoglobulin light chain amyloidosis (AL amyloidosis) is indeed a rare plasma cell disorder, yet the most common of the systemic amyloidoses. The choice of adequate treatment modality is complicated and depends dominantly on the risk stratification of these fragile patients. Immunomodulatory drugs (IMiDs) are currently used in newly diagnosed patients as well as in salvage therapy in relapsed/refractory patients. IMiDs have a pleiotropic effect on malignant cells and the exact mechanism of their action has been described recently. Thalidomide is the most ancient representative, effective but toxic. Lenalidomide seems to be more effective, nevertheless the toxicity remains high, especially in patients with renal insufficiency. Pomalidomide is the newest IMiD used in this indication with a good balance between efficacy and tolerable toxicity and represents the most promising compound. This review is focused on the evaluation of all three representatives of IMiDs and their roles in the treatment of this malignant disorder. PMID- 26806147 TI - Preterm labor and neonatal sepsis caused by intrauterine Helicobacter cinaedi infection. AB - Helicobacter cinaedi is a rare pathogen but known to cause bacteremia, cellulitis and enterocolitis. Recently, cases of involving various organs are increasingly reported such as endocarditis, meningitis, and kidney cyst infection. We report a case of intrauterine H. cinaedi infection leading preterm birth and neonatal sepsis. A 29-year-old pregnant women who was no underlying disease hospitalized due to threatened preterm labor at 22 weeks of gestation. Clinical findings showed uterine tenderness, fever, leukocytosis and elevated C-reactive protein. H. cinaedi was isolated from amniotic fluid obtained by transabdominal amniocentesis. We diagnosed as intrauterine H. cinaedi infection and administered intravenous ampicillin followed by oxytocin to terminate pregnancy. A live 446 g male infant was delivered. The patient was no signs of infection throughout postpartum course and discharged on post-delivery day 5. The neonate was admitted in neonatal intensive care unit and administered ampicillin and amikacin. H. cinaedi was isolated from umbilical cord blood culture. He has no signs of infection on day 5 but died from uncontrollable hyperglycemia and ketoacidosis on 15 days of age. H. cinaedi can cause intrauterine infection during pregnancy and lead preterm labor and neonatal sepsis. PMID- 26806148 TI - Imbalance of peripheral blood Th17 and Treg responses in children with refractory Mycoplasma pneumoniae pneumonia. AB - Mycoplasma pneumoniae (MP) pneumonia is usually a benign self-limiting disease, but some patients suffer from acute lung injury in MP infections who need to use immune-modulators with conventional antibiotic treatment. The imbalance between CD4+CD25+Foxp3+regulatory T (Treg) cells and T helper (Th17) cells has been found in a number of different inflammation and autoimmune disease, while the role of the Th17/Treg balance in MP pneumonia remains largely unknown. The aim of this study was to investigate the Th17/Treg pattern and its impact on disease severity in patients with MP pneumonia. This study involved 36 healthy control and 83 patients including 25 patients with refractory MP pneumonia and 58 patients with macrolide responsive MP pneumonia. The percentages of circulating Th17 cells and Tregs were determined by flow cytometry. The concentrations of serum Th17- and Treg-related cytokines were measured by enzyme-linked immunosorbent assay (ELISA). In comparison with that in the patients with macrolide responsive MP pneumonia and healthy control, significantly higher frequencies of Th17 cells and higher levels of IL-17 were detected in patients with refractory MP pneumonia. But there are no significant difference with the frequencies of Tregs and the levels of TGF-beta1 in the patients with refractory MP pneumonia and patients with macrolide responsive MP pneumonia. However the Th17/Treg ratio was found to be significantly higher in the patients with refractory MP pneumonia than the patients with macrolide responsive MP pneumonia. An imbalance of circulating Th17 cells and Tregs is associated with the deterioration of pulmonary injury in patients with MP infections. PMID- 26806149 TI - Diabetic foot infection in hospitalized adults. AB - BACKGROUND: Acute infections of the diabetic foot (DFI) are a common and complex condition. Patients are generally managed in the ambulatory setting and epidemiological data pertaining to hospitalized patients is lacking. The aim of this study was to analyze the epidemiology, microbiology and outcomes of hospitalized patients with DFI, who are managed at a referral center equipped with hyperbaric oxygen (HBO) therapy. METHODS: A retrospective cohort study of adult patients admitted to a tertiary referral center with DFI over a six-month period in 2013 was undertaken. Predictors of clinical outcomes and efficacy of treatment modalities were analyzed by Cox regression. RESULTS: Sixty-one patients with DFI were identified. Most patients were elderly (67 +/- 13 years), with long standing (17 +/- 9 years), poorly controlled (HbA1c 9 +/- 3%) diabetes. Most patients had polymicrobial infection (80%); specifically, anaerobic (39%) and multi or extensively-drug resistant organisms (61%). Administration of appropriate antimicrobials was delayed for >48 h in 83%. Advanced age was associated with worse outcomes. Sicker patients with severe peripheral vascular disease were managed with HBO. The use of HBO was associated with higher costs and increased functional deterioration, and did not prevent future limb amputation. CONCLUSIONS: Our study illustrates the descriptive epidemiology of hospitalized adults with DFI predominantly of polymicrobial etiology. MDROs and anaerobic organisms are common causative pathogens, and appropriate antibiotics were frequently delayed. HBO treatment may delay the need for limb amputation, but not obviate this eventual outcome. PMID- 26806150 TI - In vitro antimicrobial activity of benzoyl peroxide against Propionibacterium acnes assessed by a novel susceptibility testing method. AB - Benzoyl peroxide (BPO), a therapeutic agent for acne vulgaris, was assessed for in vitro antimicrobial activity against Propionibacterium acnes using a novel broth microdilution testing that improved BPO solubility. We searched for a suitable culture medium to measure the minimum inhibitory concentration (MIC) of BPO against P. acnes and finally found the Gifu anaerobic medium (GAM) broth supplemented with 0.1(v/v)% glycerol and 2(v/v)% Tween 80, in which BPO dissolved up to 1250 MUg/mL and P. acnes grew well. The MICs and minimum bactericidal concentrations (MBCs) of BPO against 44 clinical isolates of P. acnes collected from Japanese patients with acne vulgaris were determined by our testing method using the supplemented GAM broth. The MICs of BPO were 128 or 256 MUg/mL against all isolates of P. acnes regardless of susceptibility to nadifloxacin or clindamycin. The MBCs of BPO were also 128 or 256 MUg/mL against the same isolates. Moreover, BPO at the MIC showed a rapid bactericidal activity against P. acnes ATCC11827 in time-kill assay. In conclusion, we could develop a novel assay for the MIC and MBC determinations of BPO against P. acnes, which is reliable and reproducible as a broth microdilution testing and the present results suggest that BPO has a potent bactericidal activity against P. acnes. PMID- 26806151 TI - Evaluation of antimicrobial prophylaxis against postoperative infection after spine surgery: Limit of the first generation cephem. AB - In our department, first-generation cephem (CEZ) are generally administered for 2 days as antimicrobial prophylaxis (AMP) for spinal surgery. However, the incidence of surgical site infection (SSI) has recently increased, particularly cases involving coagulase-negative Staphylococci (CNS) as an etiologic agent. The objective was to elucidate the problems with the current AMP and the risk factors of SSI through a retrospective investigation of affected cases. The subjects were patients who underwent spine surgery at our department between August 2007 and June 2013. The subjects were divided into those who developed SSI (S group) and who did not develop SSI (non-SSI (N) group), patients who developed CNS infection in the S group was subdivided as C group, and the risk factors were investigated. The significance of each factor was analyzed using cross tabulation, and multivariate logistic regression analyses were performed with 22 of the investigation factors as explanatory variables. The incidence of SSI was 2.55%, and the etiologic agent was CNS in 17 patients. Upon comparison between the S and N groups, the presence of 3 or more underlying diseases and blood loss were extracted as significant risk factors. Upon comparison between the C and N groups, emergency surgery and intra- and postoperative steroid administration were extracted as significant risk factors, in addition to the presence of 3 or more underlying diseases and blood loss. The effect of the current AMP using first generation cephem is limited, and reconsideration of the protocol may be necessary. PMID- 26806152 TI - Genotypic characterization of multi-drug-resistant Mycobacterium tuberculosis isolates in Myanmar. AB - The number of multi-drug-resistant tuberculosis (MDR-TB) cases is rising worldwide. As a countermeasure against this situation, the implementation of rapid molecular tests to identify MDR-TB would be effective. To develop such tests, information on the frequency and distribution of mutations associating with phenotypic drug resistance in Mycobacterium tuberculosis is required in each country. During 2010, the common mutations in the rpoB, katG and inhA of 178 phenotypically MDR M. tuberculosis isolates collected by the National Tuberculosis Control Program (NTP) in Myanmar were investigated by DNA sequencing. Mutations affecting the 81-bp rifampicin (RIF) resistance-determining region (RRDR) of the rpoB were identified in 127 of 178 isolates (71.3%). Two of the most frequently affected codons were 531 and 526, with percentages of 48.3% and 14.0% respectively. For isoniazid (INH) resistance, 114 of 178 MDR-TB isolates (64.0%) had mutations in the katG in which a mutation-conferring amino acid substitution at codon 315 from Ser to Thr was the most common. Mutations in the inhA regulatory region were also detected in 20 (11.2%) isolates, with the majority at position -15. Distinct mutation rate and pattern from surrounding countries might suggest that MDR-TB has developed and spread domestically in Myanmar. PMID- 26806154 TI - Mutated MCM9 is associated with predisposition to hereditary mixed polyposis and colorectal cancer in addition to primary ovarian failure. AB - Mutations in MCM9, which encodes DNA helicase, were recently shown to cause a clinical phenotype of primary ovarian failure and chromosomal instability. MCM9 plays an essential role in homologous recombination-mediated double-strand break repair. We describe a multiplex family with early colorectal carcinoma and mixed polyposis associated with primary hypergonadotropic hypogonadism. A combination of whole genome homozygosity mapping as well as exome sequencing and targeted gene sequencing identified a homozygous c.672_673delGGinsC mutation that predicts a truncated protein, p.Glu225Lysfs*4. Our data expand the phenotypic spectrum of MCM9 mutations and suggest a link between MCM9 and inherited predisposition to mixed polyposis and early-onset colorectal cancer. PMID- 26806153 TI - The relationship between handling time and cortisol release rates changes as a function of brain parasite densities in California killifish Fundulus parvipinnis. AB - This study validated a technique for non-invasive hormone measurements in California killifish Fundulus parvipinnis, and looked for associations between cortisol (a stress hormone) and 11-ketotestosterone (KT, an androgen) release rates and the density or intensity of the trematode parasites Euhaplorchis californiensis (EUHA) and Renicola buchanani (RENB) in wild-caught, naturally infected F. parvipinnis. In experiment 1, F. parvipinnis were exposed to an acute stressor by lowering water levels to dorsal-fin height and repeatedly handling the fish over the course of an hour. Neither parasite was found to influence cortisol release rates in response to this acute stressor. In experiment 2, different F. parvipinnis were exposed on four consecutive days to the procedure for collecting water-borne hormone levels and release rates of 11-KT and cortisol were quantified. This design examined whether F. parvipinnis perceived the water borne collection procedure to be a stressor, while also exploring how parasites influenced hormone release rates under conditions less stressful than those in experiment 1. No association was found between RENB and hormone release rates, or between EUHA and 11-KT release rates. The interaction between EUHA density and handling time, however, was an important predictor of cortisol release rates. The relationship between handling time and cortisol release rates was negative for F. parvipinnis harbouring low or intermediate density infections, and became positive for fish harbouring high densities of EUHA. PMID- 26806155 TI - Iterative categorization (IC): a systematic technique for analysing qualitative data. AB - The processes of analysing qualitative data, particularly the stage between coding and publication, are often vague and/or poorly explained within addiction science and research more broadly. A simple but rigorous and transparent technique for analysing qualitative textual data, developed within the field of addiction, is described. The technique, iterative categorization (IC), is suitable for use with inductive and deductive codes and can support a range of common analytical approaches, e.g. thematic analysis, Framework, constant comparison, analytical induction, content analysis, conversational analysis, discourse analysis, interpretative phenomenological analysis and narrative analysis. Once the data have been coded, the only software required is a standard word processing package. Worked examples are provided. PMID- 26806156 TI - Circulating Fibroblast Growth Factor 21 Is A Sensitive Biomarker for Severe Ischemia/reperfusion Injury in Patients with Liver Transplantation. AB - Hepatic ischemia/reperfusion (I/R) injury is a major cause of morbidity and mortality after liver surgery. Therefore, it is important to identity reliable biomarkers to assist early diagnosis of hepatic I/R injury. This study aimed to investigate the potential of serum levels of fibroblast growth factor 21 (FGF21) as a biomarker for hepatic I/R injury in patients with liver transplantation. Two independent cohorts of liver transplantation patients were recruited for determination of serum levels of FGF21, ALT, and AST. The results demonstrated that serum FGF21 at 2 hours post-reperfusion in cohort-1 exhibited an approximately 20-fold elevation relative to those in healthy subjects. In blood samples dynamically collected in cohort-2, a dramatic increase in serum FGF21 levels (~25-fold) was observed at two hours after surgery, whereas the peak levels of serum ALT and AST were detected only after 24 hours. Temporal correlation analysis demonstrated a significant association of peak serum levels of FGF21 at 2 hours with the magnitude of the increase in both serum ALT and AST levels at 24 hours post transplantation. In conclusion, serum FGF21 may represent a sensitive and specific prognostic biomarker for early detection of I/R injury in patients with liver transplantation. PMID- 26806157 TI - Computational approaches to detect allosteric pathways in transmembrane molecular machines. AB - Many of the functions of transmembrane proteins involved in signal processing and transduction across the cell membrane are determined by allosteric couplings that propagate the functional effects well beyond the original site of activation. Data gathered from breakthroughs in biochemistry, crystallography, and single molecule fluorescence have established a rich basis of information for the study of molecular mechanisms in the allosteric couplings of such transmembrane proteins. The mechanistic details of these couplings, many of which have therapeutic implications, however, have only become accessible in synergy with molecular modeling and simulations. Here, we review some recent computational approaches that analyze allosteric coupling networks (ACNs) in transmembrane proteins, and in particular the recently developed Protein Interaction Analyzer (PIA) designed to study ACNs in the structural ensembles sampled by molecular dynamics simulations. The power of these computational approaches in interrogating the functional mechanisms of transmembrane proteins is illustrated with selected examples of recent experimental and computational studies pursued synergistically in the investigation of secondary active transporters and GPCRs. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. PMID- 26806159 TI - A computational study of ion current modulation in hVDAC3 induced by disulfide bonds. AB - The human VDAC channel exists in three isoforms characterized by high sequence homology and structural similarity. Yet the function and mode of action of hVDAC3 are still elusive. The presence of six surface cysteines exposed to the oxidizing environment of the mitochondrial inter-membrane space suggests the possible establishment of intramolecular disulfide bonds. Two natural candidates for disulfide bridge formation are Cys2 and Cys8 that, located on the flexible N terminal domain, can easily come in contact. A third potentially important residue is Cys122 that is close to Cys2 in the homology model of VDAC3. Here we analyzed the impact of SS bonds through molecular dynamics simulations of derivatives of hVDAC3 (dubbed SS-2-8, SS-2-122, SS-8-122) including a single disulfide bond. Simulations showed that in SS-8-122, the fragment 1-7 crosses the top part of the barrel partially occluding the pore and causing a 20% drop of conductance. In order to identify other potential channel-occluding disulfide bonds, we used a set of neural networks and structural bioinformatics algorithms, after filtering with the steric constraints imposed by the 3D-structure. We identified other three species, namely SS-8-65, SS-2-36 and SS-8-36. While the conductance of SS-8-65 and SS-2-36 is about 30% lower than that of the species without disulfide bonds, the conductance of SS-8-36 was 40-50% lower. The results show how VDAC3 is able to modulate its pore size and current by exploiting the mobility of the N-terminal and forming, upon external stimuli, disulfide bridges with cysteine residues located on the barrel and exposed to the inter-membrane space. PMID- 26806158 TI - Polyglutamine aggregates impair lipid membrane integrity and enhance lipid membrane rigidity. AB - Lipid membranes are suggested as the primary target of amyloid aggregates. We study aggregates formed by a polyglutamine (polyQ) peptide, and their disruptive effect on lipid membranes. Using solution atomic force microscopy (AFM), we observe polyQ oligomers coexisting with short fibrils, which have a twisted morphology that likely corresponds to two intertwined oligomer strings. Fourier transform infrared spectroscopy reveals that the content of beta-sheet enriched aggregates increases with incubation time. Using fluorescence microscopy, we find that exposure to polyQ aggregates results in deflated morphology of giant unilamellar vesicles. PolyQ aggregates induced membrane disruption is further substantiated by time-dependent calcein leakage from the interior to the exterior of lipid vesicles. Detailed structural and mechanical perturbations of lipid membranes are revealed by solution AFM. We find that membrane disruption by polyQ aggregates proceeds by a two-step process, involving partial and full disruption. In addition to height contrast, the resulting partially and fully disrupted bilayers have distinct rigidity and adhesion force properties compared to the intact bilayer. Specifically, the bilayer rigidity increases as the intact bilayer becomes partially and fully disrupted. Surprisingly, the adhesion force first decreases and then increases during the disruption process. By resolving individual fibrils deposited on bilayer surface, we show that both the length and the number of fibrils can increase with incubation time. Our results highlight that membrane disruption could be the molecular basis of polyQ aggregates induced cytotoxicity. PMID- 26806161 TI - Viral channel forming proteins--How to assemble and depolarize lipid membranes in silico. AB - Viral channel forming proteins (VCPs) have been discovered in the late 70s and are found in many viruses to date. Usually they are small and have to assemble to form channels which depolarize the lipid membrane of the host cells. Structural information is just about to emerge for just some of them. Thus, computational methods play a pivotal role in generating plausible structures which can be used in the drug development process. In this review the accumulation of structural data is introduced from a historical perspective. Computational performances and their predictive power are reported guided by biological questions such as the assembly, mechanism of function and drug-protein interaction of VCPs. An outlook of how coarse grained simulations can contribute to yet unexplored issues of these proteins is given. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. PMID- 26806160 TI - Studies on the interactions of bisphenols with anionic phospholipids of decomposer membranes in model systems. AB - Bisphenol A (BPA) and other bisphenols constitute a class of organic pollutants, which because of their estrogenic properties, low dose activity and bioaccumulation pose considerable risk for public health as well as for the environment. Accumulated in the sediment bisphenols can endanger the decomposers' populations being incorporated into their cellular membranes; however, the mechanism of their membrane activity is unknown. Therefore, to study these phenomena we applied anionic phospholipid Langmuir monolayers as simple but versatile models of decomposers biomembranes. Phosphatidylglycerols and cardiolipins are not only the main components of bacterial membranes but also of crucial importance in mitochondrial and thylakoid membranes in eukaryotic cells. In our investigations we applied five compounds of the bisphenol class most commonly detected in the environment. To characterize the bisphenols-model membrane interactions we applied multiple mutually independent methods of physical chemistry; namely: the Langmuir monolayer technique, surface potential measurements, Brewster angle microscopy for the visualization of the monolayers' texture and grazing incidence X-ray diffraction for the discussion of the phospholipids packing within the monolayers. Our studies indicated that all the investigated bisphenols interact with the model membrane, but the strength of the interactions is dependent on the bisphenol structure and hydrophobicity and the fluidity of the model membranes. We proved that bisphenol S often treated as the least toxic BPA analog can also be incorporated to the model membranes changing their structure and fluidity. PMID- 26806162 TI - Stomatin-like protein 2 of turbot Scopthalmus maximus: Gene cloning, expression profiling and immunoregulatory properties. AB - Stomatin-like protein 2 (SLP-2) is a novel and unusual member of the stomatin gene superfamily. In this study, we obtained a full-length SLP-2 (SmSLP-2) cDNA from turbot (Scopthalmus maximus) spleen cDNA library. The cDNA sequence of SmSLP 2 contains a 5'-UTR of 107 bp, an ORF of 1050 bp, and a 3'-UTR of 959 bp. The ORF encodes a putative protein of 349 residues, which has a calculated molecular mass of 38.7 kDa. The SmSLP-2 protein possesses a prohibitin-homology (PHB) domain (residues 40 to 198) and shares 72.4-87.6% overall sequence identity with that of the teleost species. The highest expression of SmSLP-2 mRNA was found in the skin, followed by the head kidney, gut, spleen, liver, heart, gill and muscle. Moreover, both viral and bacterial pathogen infection resulted in the up regulation of SmSLP-2 mRNA in the turbot head kidney and spleen in vivo. Subcellular localization analysis indicated that the SmSLP-2 proteins are mainly located in the peripheral membrane of ZF4 cells. This study also demonstrated that SmSLP-2 modulates IL-2 expression via active NFkappaB signaling pathway, and is possibly involved in host immune defense against bacterial and viral pathogens. PMID- 26806163 TI - Development and characterization of a cell line from tilapia head kidney with melanomacrophage characteristics. AB - A novel cell line THK, derived from the tilapia head kidney, was developed and characterized. The THK cell line comprised fibroblastoid cells that markedly proliferated in Leibovitz L-15 medium containing 2%-15% fetal bovine serum (FBS) at 20 degrees C-35 degrees C. Cell proliferation was dependent on the FBS concentration, and the optimal temperature for proliferation ranged between 25 degrees C and 30 degrees C. THK cells were characterized for the presence of phagocytic activity, acid phosphatase, alkaline phosphatase, alpha-naphthyl acetate esterase, lipofuscin, and tyrosinase. Transcripts of CD33, CD53, CD82, CD205, macrophage colony stimulating factor receptor, GATA2, and GATA3 that are specific for leucocytes or monocytes/macrophages or both were detected in the THK cells through PCR. However, THK cells lacked for CD83, a specific marker for dendritic cells. The results indicated that the fibroblastoid THK cells were melanomacrophage-related progenitors. PCR revealed that the THK cells exhibited the transcripts of toll-like receptor 1 (TLR1), TLR2, TLR3, and CD200, of which concern with immunity as well as the transcripts of vascular endothelial growth factor receptor 3, angiomotin, and angiopoietin-like protein 2 that associate with angiogenesis regulation and macrophage proliferation. THK cells were subcultured more than 90 times and can be useful for investigating the development and functioning of the teleostean innate immune system. PMID- 26806164 TI - Down-regulation apoptosis signal-regulating kinase 1 gene reduced the Litopenaeus vannamei hemocyte apoptosis in WSSV infection. AB - Apoptosis signal-regulating kinase 1 (ASK1), a mitogen-activated protein kinase kinase kinase, is crucial in various cellular responses. In the present study, we identified and characterized an ASK1 homolog from Litopenaeus vannamei (LvASK1). The full-length cDNA of LvASK1 was 5400 bp long, with an open reading frame encoding a putative 1420 amino acid protein. LvASK1 was highly expressed in muscle, hemocyte, eyestalk and heart. Real-time RT-PCR analysis showed that the expression of the LvASK1 was upregulated during the white spot syndrome virus (WSSV) challenge. The knocked-down expression of LvASK1 by RNA interference significantly reduced the apoptotic ratio of the hemocytes collected from WSSV infected L. vannamei. Furthermore, the down-regulation of LvASK1 also decreased the cumulative mortality of WSSV-infected L. vannamei. These results suggested that down-regulation of LvASK1 decreased the apoptotic rate of hemocytes in WSSV infected shrimp, and that it could contribute to the reduction of cumulative mortality in WSSV-infected L. vannamei. PMID- 26806165 TI - Identification and function analysis of the three dsRBMs in the N terminal dsRBD of grass carp (Ctenopharyngodon idella) PKR. AB - The protein kinase R (PKR) can inhibit protein translation and lead to apoptosis under the circumstances of virus invasion and multiple other stress conditions. PKR is a dsRNA binding protein with a dsRBD and a kinase domain (KD). dsRBD is mostly composed of two (in mammal PKR) or three (in some fish PKR) dsRNA binding motifs (dsRBMs). Multiple sequences alignment and Phylogenetic analysis indicate that the three dsRBMs of fish PKR share analogous structure but show to be divergence origination. In this study, we have identified and analyzed the three dsRBMs from grass carp (Ctenopharyngodon idellus) PKR (CiPKR), which was cloned previously in our laboratory. dsRBMs of CiPKR have two or three conserved regions involved in dsRNA binding. Among the three dsRBMs, dsRBM1 was peculiar to some fish PKRs, while dsRBM2 and dsRBM3 were closely related to the dsRBM1 and dsRBM2 of mammal PKRs respectively. Dimerization assay indicated that dsRBM1 and dsRBM2 formed not only homo-dimer but also homo-multimer; whereas dsRBM3 formed merely homo-dimer. Meanwhile, dsRBM1-2, dsRBM2-3 and dsRBM1-2-3 could homo-dimerize and homo-multimerize also. Poly I:C pull-down assay showed that the binding of dsRBM to Poly I:C needed two or three dsRBMs to cooperate in vitro, meaning one dsRBM from CiPKR could not bind to dsRNA efficiently. To further investigate the effect of dsRBM on the function of CiPKR, we constructed pcDNA3.1/CiPKR-wt and a series of CiPKR mutants recombined plasmids including pcDNA3.1/CiPKR-DeltadsRBM2-3, pcDNA3.1/CiPKR-DeltadsRBM1,3, pcDNA3.1/CiPKR-DeltadsRBM1-2, pcDNA3.1/CiPKR DeltadsRBM3, pcDNA3.1/CiPKR-DeltadsRBM1. The recombined plasmids respectively were co-transfected with plasmid PGL3 promoter into CIK cells. In comparison with the control group, the luciferase translation inhibitions were 78.7%, 15%, 0, 0.5%, 61.8%, 67.3% respectively. The results indicated that the protein translation inhibition caused by CiPKR mutants with only one dsRBM were very weak, while those with two or three dsRBMs inhibited the protein translation powerfully. Cell viability were 34.2%, 98.2%, 112%, 108%, 50.3%, 47.5% respectively after transfected with pcDNA3.1/CiPKR-wt, pcDNA3.1/CiPKR-DeltadsRBM2 3, pcDNA3.1/CiPKR-DeltadsRBM1,3, pcDNA3.1/CiPKR-DeltadsRBM1-2, pcDNA3.1/CiPKR DeltadsRBM3, pcDNA3.1/CiPKR-DeltadsRBM1 in order into CIK cells for 48 h. The results from cell counting also indicated that transfection of CiPKR-wt and the mutants CiPKR-DeltadsRBM3, CiPKR-DeltadsRBM1 could inhibit the protein translation and facilitated the decrease of CIK cells number. In conclusion, our observations suggested that two dsRBMs ranking in tandem at N terminal were essential for the function of CiPKR, and the presence of the extra dsRBM1 enhanced its function. PMID- 26806166 TI - The immunological capacity in the larvae of Pacific oyster Crassostrea gigas. AB - As the immune system has not fully developed during early developmental stages, bivalve larvae are more susceptible for pathogens, which frequently leads to the significant mortality in hatcheries. In the present study, the development of immune system and its response against bacteria challenge were investigated in order to characterize the repertoire of immunological capacity of Pacific oyster Crassostrea gigas during the ontogenesis. The phagocytosis was firstly observed in the early D-veliger larvae (17 hpf), especially in their velum site, which indicated the appearance of functional hemocytes during early D-veliger larvae stage. The whole-mount immunofluorescence assay of three pattern recognition receptors (integrin beta-1, caspase-3 and C-type lectin 3) and one immune effector gene (IL17-5) was performed in blastula, early D-veliger and umbo larvae, suggested that velum and digestive gland were the potential sites of immune system in the larvae. The lowest activities of antioxidant enzymes (superoxide dismutase and catalase) and hydrolytic enzyme (lysozyme), as well as descended expression levels of 12 immune genes at the transition between embryogenesis and planktonic, indicated that the larvae at hatching (9 hpf) were in hypo-immunity. While the ascending activities of enzymes and expression levels of seven immune genes during the trochophore stage (15 hpf) suggested the initiation of immune system. The steadily increasing trend of all the 12 candidate genes at the early umbo larvae (120 h) hinted that the immune system was well developed at this stage. After bacterial challenge, some immune recognition (TLR4) and immune effector (IL17-5 and defh2) genes were activated in blastula stage (4 hpf), and other immune genes were up regulated in D-veliger larvae, indicating that the zygotic immune system could respond earlier against the bacterial challenge during its development. These results indicated that the cellular and humoral immune components appeared at trochophore stage, and the cellular immune system was activated with its occurrence, while the humoral immune system executed until the early umbo larval stage. The immune system emerged earlier to aid larvae in defending bacterial challenge during the early stages of oyster development. PMID- 26806167 TI - Bat consumption in Thailand. AB - BACKGROUND: Human consumption of bats poses an increasing public health threat globally. Communities in which bat guano is mined from caves have extensive exposure to bat excreta, often harvest bats for consumption, and are at risk for bat-borne diseases. METHODS: This rapid ethnographic study was conducted in four provinces of Thailand (Ratchaburi, Sakaeo, Nakorn Sawan, and Phitsanulok), where bat guano was mined and sold during the period April-August 2014. The aim of this study was to understand behaviors and risk perceptions associated with bat conservation, exposure to bats and their excreta, and bat consumption. Sixty seven respondents playing various roles in bat guano mining, packaging, sale, and use as fertilizer participated in the study. Data were collected through interviews and/or focus group discussions. RESULTS: In spite of a bat conservation program dating back to the 1980s, the benefits of conserving bats and the risks associated with bat consumption were not clear and infrequently articulated by study respondents. DISCUSSION: Since bat consumption continues, albeit covertly, the risk of bat-borne diseases remains high. There is an opportunity to reduce the risk of bat-borne diseases in guano-mining communities by strengthening bat conservation efforts and raising awareness of the health risks of bat consumption. Further research is suggested to test behavior change strategies for reducing bat consumption. PMID- 26806168 TI - Long-Term Durability of Carpentier-Edwards Magna Ease Valve: A One Billion Cycle In Vitro Study. AB - BACKGROUND: Durability and hemodynamic performance are top considerations in selecting a valve for valve replacement surgery. This study was conducted in order to evaluate the long-term mechanical durability and hydrodynamic performance of the Carpentier-Edwards PERIMOUNT Magna Ease Bioprostheses, through 1 billion cycles (equivalent to 25 years). METHODS: In vitro valve hydrodynamic performance, durability, and quantitative flow visualization were conducted in accordance with ISO 5840:2005 heart valve standard. The study valves were subjected to accelerated valve cycling to an equivalent of 25 years of wear. Hydrodynamic evaluations at intervals of 100 million cycles (2.5 years) were performed on the study valves. New uncycled Magna Ease valves were used as hydrodynamic controls in this study. A quantitative assessment of the fluid motion downstream of the control and study valves was performed using particle image velocimetry. The results between the test and control valves were compared to assess valve performance after an equivalent of 25 years of wear. RESULTS: All study valves met the ISO 5840 requirements for effective orifice area, 1.81 +/- 0.06 cm(2) and 2.06 +/- 0.17 cm(2), and regurgitant fraction, 1.11% +/- 0.87% and 2.5% +/- 2.34%, for the 21 mm and 23 mm study valves, respectively. The flow characterization of the control valves and the billion-cycle valves demonstrated that the valves exhibited similar flow characteristics. The velocity and shear stress fields were similar between the control and study valves. CONCLUSIONS: The Magna Ease valves demonstrated excellent durability and hydrodynamic performance after an equivalent of 25 years of simulated in vitro wear. All study valves successfully endured 1 billion cycles of simulated wear, 5 times longer than the standard requirement for a tissue valve as stipulated in ISO 5840. PMID- 26806169 TI - Video-Assisted Mediastinoscopic Lymphadenectomy for Staging Non-Small Cell Lung Cancer. AB - BACKGROUND: The aim of this study was to evaluate the results of video-assisted mediastinoscopic lymphadenectomy (VAMLA) for staging of non-small cell lung cancer (NSCLC). METHODS: This was a prospective observational study of all consecutive VAMLAs performed from January 2010 to April 2015 for staging NSCLC. For left lung cancers, extended cervical videomediastinoscopy was added to explore the subaortic and paraaortic nodes. Patients with negative VAMLA results underwent tumor resection and lymphadenectomy of the remaining nodes. Those with N2-3 disease underwent chemoradiation. The rate of unsuspected pathologic (p)N2-3 was analyzed in the global series and in the subgroups of patients according to their nodal status diagnosed by imaging and metabolic techniques. RESULTS: One hundred sixty VAMLAs were performed for staging NSCLC (138 tumors were clinical (c)N0-1 based on imaging techniques). The rate of unsuspected N2-3 disease was 18% for the whole series: 40.7% for cN1, 22.2% for cN0 and tumor size greater than or equal to 3 cm, and 6.4% for cN0 and tumor size less than 3 cm. Staging values were sensitivity, 0.96 (95% confidence interval [CI], 0.81-99.3); specificity, 1 (95% CI, 0.97-1); positive predictive value, 1 (95% CI, 0.87-1); negative predictive value, 0.99 (95% CI, 0.95-0.99); and diagnostic accuracy, 0.99 (95% CI, 0.96-0.99). The complication rate was 5.9%. CONCLUSIONS: VAMLA is a feasible and highly accurate technique. The high rate of unsuspected mediastinal node disease diagnosed by VAMLA in patients with cN1 or cN0 disease and tumor size larger than 3 cm suggests that preresection lymphadenectomies should be included in the current staging algorithms. PMID- 26806172 TI - Delivering anti-cancer drugs with endosomal pH-sensitive anti-cancer liposomes. AB - Numerous prior studies have been reported on the use of pH-sensitive drug carriers such as micelles, liposomes, peptides, polymers, nanoparticles, etc. that are sensitive to the acidic (pH = ~6.5) microenvironments of tumor tissues. Such systems have been primarily used in the past as effective drug/gene/microRNA carriers for releasing their anti-cancer payloads selectively to tumor cells/tissues. Herein, we report on the development of new liposomal drug carriers prepared from glutamic acid backbone-based cationic amphiphiles containing both endosomal pH-sensitive histidine as well as cellular uptake & solubility enhancing guanidine moieties in their polar head-group regions. The most efficient one among the four presently described endosomal pH-sensitive liposomal drug carriers not only effectively delivers potent anti-cancer drugs (curcumin & paclitaxel) to mouse tumor, but also significantly contributes to inhibiting mouse tumor growth. The findings in the in vitro mechanistic studies are consistent with apoptosis of tumor cells being mediated through increased cell cycle arrest in the G2/M phase. Findings in the FRET assay and in vitro drug release studies conducted with the liposomes of the most efficient pH-sensitive lipid demonstrated its pH dependent fusogenic and controlled curcumin release properties. Importantly, the presently described liposomal formulation of curcumin & paclitaxel enhanced overall survivability of tumor bearing mice. To the best of our knowledge, the presently described system (curcumin, paclitaxel and liposomal carrier itself) is the first of its kind pH-sensitive liposomal formulation of potent chemotherapeutics in which the liposomal drug itself exhibits significant mouse tumor growth inhibition properties. PMID- 26806170 TI - Perceived Appropriateness of Shared Decision-making in the Emergency Department: A Survey Study. AB - OBJECTIVES: The objective was to describe perceptions of practicing emergency physicians (EPs) regarding the appropriateness and medicolegal implications of using shared decision-making (SDM) in the emergency department (ED). METHODS: We conducted a cross-sectional survey of EPs at a large, national professional meeting to assess perceived appropriateness of SDM for different categories of ED management (e.g., diagnostic testing, treatment, disposition) and in common clinical scenarios (e.g., low-risk chest pain, syncope, minor head injury). A 21 item survey instrument was iteratively developed through review by content experts, cognitive testing, and pilot testing. Descriptive and multivariate analyses were conducted. RESULTS: We approached 737 EPs; 709 (96%) completed the survey. Two-thirds (67.8%) of respondents were male; 51% practiced in an academic setting and 44% in the community. Of the seven management decision categories presented, SDM was reported to be most frequently appropriate for deciding on invasive procedures (71.5%), computed tomography (CT) scanning (56.7%), and post ED disposition (56.3%). Among the specific clinical scenarios, use of thrombolytics for acute ischemic stroke was felt to be most frequently appropriate for SDM (83.4%), followed by lumbar puncture to rule out subarachnoid hemorrhage (73.8%) and CT head for pediatric minor head injury (69.9%). Most EPs (66.8%) felt that using and documenting SDM would decrease their medicolegal risk while a minority (14.2%) felt that it would increase their risk. CONCLUSIONS: Acceptance of SDM among EPs appears to be strong across management categories (diagnostic testing, treatment, and disposition) and in a variety of clinical scenarios. SDM is perceived by most EPs to be medicolegally protective. PMID- 26806173 TI - Improvement and transcriptome analysis of root architecture by overexpression of Fraxinus pennsylvanica DREB2A transcription factor in Robinia pseudoacacia L. 'Idaho'. AB - Transcription factors play a key role to enable plants to cope with abiotic stresses. DREB2 regulates the expression of several stress-inducible genes and constitutes major hubs in the water stress signalling webs. We cloned and characterized a novel gene encoding the FpDREB2A transcription factor from Fraxinus pennsylvanica, and a yeast activity assay confirmed its DRE binding and transcription activation. Overexpression of FpDREB2A in R. pseudoacacia showed enhanced resistance to drought stress. The transgenic plant survival rate was significantly higher than that of WT in soil drying and re-watering treatments. Transgenic lines showed a dramatic change in root architecture, and horizontal and vertical roots were found in transgenic plants compared to WT. The vertical roots penetrated in the field soil to more than 60 cm deep, while horizontal roots expanded within the top 20-30 cm of the soil. A physiological test demonstrated that chlorophyll contents were more gradually reduced and that soluble sugars and proline levels elevated more sharply but malondialdehyde level stayed the same (P < 0.05). Plant hormone levels of abscisic acid and IAA were higher than that of WT, while gibberellins and zeatin riboside were found to be lower. The root transcriptomes were sequenced and annotated into 2011 differential expression genes (DEGs). The DEGs were categorized in 149 pathways and were found to be involved in plant hormone signalling, transcription factors, stimulus responses, phenylalanine, carbohydrate and other metabolic pathways. The modified pathways in plant hormone signalling are thought to be the main cause of greater horizontal and vertical root development, in particular. PMID- 26806174 TI - Comparative effectiveness of standard CPR vs active compression-decompression CPR with CardioPump for treatment of cardiac arrest. AB - BACKGROUND: Despite all of the studies conducted on cardiopulmonary resuscitation (CPR), the mortality rate of cardiac arrest patients is still high. This has led to a search for alternative methods. One of these methods is active compression decompression CPR (ACD-CPR) performed with the CardioPump. OBJECTIVE: The differences in the restoration of spontaneous circulation; the 1-, 7-, and 30-day survival rates; and hospital discharge rates between conventional CPR and ACD-CPR performed with CardioPump were investigated. In addition, the differences between the 2 methods with respect to complications were also investigated. METHODS: Our study was a prospective, randomized medical device study with a case-control group. Cardiac arrest cases brought to our emergency medicine clinic by the 112 emergency ambulances from out of hospital and patients who had developed cardiac arrest inhospital clinics between April 2015 and September 2015 were included in our study. For randomization, standard CPR was performed on odd days of each month, and CPR using CardioPump was performed on the even days of each month. RESULTS: A total of 181 patients were included in our study. The number of patients who received conventional CPR was determined as 86 (47.5%), and the number of patients who received CPR using the CardioPump was determined as 95 (52.5%). We did not identify any difference between conventional CPR and CardioPump ACD-CPR with respect to restoration of spontaneous circulation, discharge rates, and the 1-, 7-, and 30-day survival rates. (P=.384, P=.601, P=.997, P=.483, and P=.803, respectively) The complication rate was higher in the patient group that received conventional CPR (P<.001). CONCLUSION: As a result of our study, we did not obtain any evidence supporting the replacement of conventional CPR with ACD-CPR performed using CardioPump. PMID- 26806175 TI - Thrombotic complications following the administration of high-dose prothrombin complex concentrate for acute warfarin reversal. PMID- 26806176 TI - Renal impairment and outcome in patients with takotsubo cardiomyopathy. AB - OBJECTIVES: The objectives were to ascertain the prevalence of renal impairment among patients with a takotsubo cardiomyopathy (TTC) episode and whether clinical outcomes are related to renal function. METHODS: A total of 108 consecutive subjects with TTC were enrolled in a multicenter registry and followed for a mean period of 429 days. Renal function was evaluated during hospitalization in terms of acute kidney injury/failure and estimated glomerular filtration rate (eGFR). Incidence of death, rehospitalization, and recurrence of TTC during follow-up was recorded. RESULTS: Raised creatinine levels can be found during hospitalizations for TTC episodes (analysis of variance P<.001). Incidence of acute kidney injury was 10%; that of acute kidney failure was 1%. Admission eGFR levels were proportional to the duration of hospitalization (r = -0.28, P<.01). Estimated GFR nadir values were related to adverse events at follow-up (log-rank P<.001). The hazard ratio of adverse events at follow-up in subjects with severe renal impairment (nadir eGFR <30 mL/[min 1.73 m(2)]) vs those with eGFR >60 mL/(min 1.73 m(2)) was 1.817 (95% confidence interval, 1.097-3.009; P<.05). CONCLUSIONS: Raised creatinine levels and impaired renal function may be found in patients with TTC. Lower eGFR values during hospitalization are associated with longer hospitalizations and higher rates of adverse events at follow-up. Renal function during a TTC episode should be carefully evaluated. PMID- 26806177 TI - The impact of body mass index on patient survival after therapeutic hypothermia after resuscitation. AB - OBJECTIVES: Therapeutic hypothermia improves survival in patients after cardiac arrest, yet the impact of body mass index (BMI) on survival is lesser known. We hypothesized that nonobese patients would have greater survival post-therapeutic hypothermia than obese patients. METHODS: We retrospectively evaluated 164 patients who underwent therapeutic hypothermia after resuscitation for cardiac arrest from January 2012 to September 2014. Logistic regression analysis was used to assess for survival based upon BMI and comorbidities (odds ratio, 95% confidence interval). RESULTS: Forty-one percent of patients were obese. Obese patients presented less frequently with ventricular fibrillation (P=.046) but had similar rates of pulseless electrical activity (P=.479) and ventricular tachycardia (P=.262) to nonobese patients. In multivariable analysis, BMI less than 30 kg/m(2), hypertension, presence of pacemaker/implantable cardioverter defibrillator, high glomerular filtration rate, and low neuron-specific enolase were all associated with increased survival post-therapeutic hypothermia, respectively: 0.36 (0.16-0.78), 0.28 (0.12-0.66), 0.23 (0.08-0.62), 0.25 (0.11 0.56), and 0.37 (0.14-0.96). Other comorbidities demonstrated no association with survival. CONCLUSIONS: Body mass index at least 30 kg/m(2) compared with BMI less than 30 kg/m(2) was a significant risk factor for mortality post-therapeutic hypothermia protocol. Absence of history of hypertension, lack of pacemaker/implantable cardioverter-defibrillator, high neuron-specific enolase, and renal disease had greater associations with death. Larger studies will be needed to validate these findings. PMID- 26806178 TI - Plesiomonas shigelloides meningitis in an adult in the ED. PMID- 26806179 TI - Green tea and cardiac arrest: just in case! PMID- 26806180 TI - Brucella-induced sublingual abscess causes acute shortness of breath. PMID- 26806181 TI - A novel mechanism for the biogenesis of outer membrane vesicles in Gram-negative bacteria. AB - Bacterial outer membrane vesicles (OMVs) have important biological roles in pathogenesis and intercellular interactions, but a general mechanism of OMV formation is lacking. Here we show that the VacJ/Yrb ABC (ATP-binding cassette) transport system, a proposed phospholipid transporter, is involved in OMV formation. Deletion or repression of VacJ/Yrb increases OMV production in two distantly related Gram-negative bacteria, Haemophilus influenzae and Vibrio cholerae. Lipidome analyses demonstrate that OMVs from VacJ/Yrb-defective mutants in H. influenzae are enriched in phospholipids and certain fatty acids. Furthermore, we demonstrate that OMV production and regulation of the VacJ/Yrb ABC transport system respond to iron starvation. Our results suggest a new general mechanism of OMV biogenesis based on phospholipid accumulation in the outer leaflet of the outer membrane. This mechanism is highly conserved among Gram-negative bacteria, provides a means for regulation, can account for OMV formation under all growth conditions, and might have important pathophysiological roles in vivo. PMID- 26806183 TI - Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. AB - The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm recommends intra-articular (IA) hyaluronic acid (HA) for management of knee osteoarthritis (OA) as second-line treatment in patients who remain symptomatic despite use of non-steroidal anti inflammatory drugs (NSAIDs). This recommendation is based upon accumulating evidence that IA HA provides a significant benefit in knee OA. There is good evidence that IA HA injections reduce pain and increase function in knee OA, and the benefits are long-lasting as compared with IA corticosteroids. Evidence from real-life studies of repeat courses of IA HA demonstrates an improvement in pain or function lasting up to 40 months (12 months after the last injection cycle), a reduction in use of concomitant analgesia by up to 50%, and suggests that there may be a delay in the need for total knee replacement (TKR) of around 2 years. The clinical benefit of IA HA on knee OA may be 2-fold: (i) mechanical viscosupplementation of the joint (allowing lubrication and shock absorption) and (ii) the re-establishment of joint homeostasis through induction of endogenous HA production, which continues long after the exogenous injection has left the joint. The magnitude of the clinical effect may be different for different HA products, but this has not been proven so far and requires further investigation. IA HA injections are generally considered to be safe, although a slightly higher number of cases of local reactions and post-injection non-septic arthritis has been reported with high molecular weight cross-linked HAs. The use of IA HA in knee OA patients with mild-moderate disease, and for more severe patients wishing to delay TKR surgery, is recommended by the ESCEO task force. Further investigation into the OA patient types most likely to benefit from IA HA is warranted. Viscosupplementation with IA HA is a safe and effective component of the multi-modal management of knee OA. PMID- 26806182 TI - Retinal vessel diameters in a Japanese population: the Locomotive Syndrome and Health Outcome in Aizu Cohort Study. AB - PURPOSE: To describe the relationship between retinal vascular calibre and cardiovascular risk factors in a Japanese population. METHODS: The Locomotive Syndrome and Health Outcome in Aizu Cohort Study is a population-based, cross sectional survey that included 2346 persons (56.1% of the eligible population) aged 40 to 74 years old. Retinal vascular calibre was measured from digital retinal photographs using a validated standardized protocol. Data on major cardiovascular risk factors were collected from all participants. RESULTS: Of the 1787 participants with available retinal vascular calibre data, the mean retinal arteriolar calibre (CRAE) was 141.6 +/- 18.6 MUm, the mean venular calibre (CRVE) was 209.3 +/- 26.1 MUm, and the mean arteriole-to-venule ratio was 0.68 +/- 0.08. A smaller CRAE was associated with male sex, increasing quartiles of systolic blood pressure and diastolic blood pressure, history of hypertension, current alcohol intake and higher quartiles of serum creatinine. A larger CRAE was associated with increasing quartiles of total cholesterol. A larger CRVE was associated with current cigarette smoking. Multivariate analyses showed that a smaller CRAE was associated with male sex, elevated mean arterial blood pressure and a history of hypertension; and a larger CRVE was associated with cigarette smoking. CONCLUSIONS: The results of this study suggest that a narrowed diameter of the retinal arteriole in Japanese people is related to hypertension and sex (male) and that an enlarged retina venular diameter is related to a history of smoking. The pattern of these associations is similar to that in white populations and other Asian populations. PMID- 26806184 TI - Efficacy and safety of oral NSAIDs and analgesics in the management of osteoarthritis: Evidence from real-life setting trials and surveys. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are at the cornerstone of treatment for osteoarthritis (OA). In recent years, the widespread use of oral NSAIDs has been called into question due to the appearance of significant upper gastrointestinal (GI) complications and cardiovascular (CV) adverse events (AEs). However, NSAIDs are non-homogeneous, and there are noticeable differences between them in AE risk for GI and CV events. Nevertheless, if properly prescribed oral NSAIDs can provide an effective and safe treatment for OA in real-life situations. The identification of patients with significant CV and/or GI risk is critical, and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm provides guidance on appropriate treatments for OA patients with elevated risk. Among non-selective NSAIDs, ibuprofen and naproxen seem preferable to diclofenac, the latter being associated with higher CV risk. Recommendation has been made by some that naproxen may be the preferred agent in patients at high CV risk because of its lower risk of CV events. Low dose celecoxib (200mg/day) is also associated with a lower risk of CV events compared with other coxibs. In addition, drugs with a demonstrated low GI risk profile may be of benefit, such as coxibs and nabumetone. Among patients who fail to respond adequately to sequential ESCEO algorithm Step 1 and Step 2 treatments, the short-term use of weak opioids, such as tramadol, for severely symptomatic OA patients is recommended. Although studies exploring the efficacy of tramadol in OA are limited, there is good evidence that tramadol works if prescribed properly. The sustained-release (SR) formulation of tramadol is preferred as it avoids the peak plasma concentrations reached with immediate-release tramadol, and is believed to reduce the incidence of AEs. Furthermore, slow upwards titration of tramadol SR is recommended to improve tolerability and minimize treatment discontinuations. PMID- 26806186 TI - Optimizing the management of osteoarthritis-Transitioning evidence-based guidelines into practical guidance for real-world clinical practice. PMID- 26806185 TI - The role of diet and exercise and of glucosamine sulfate in the prevention of knee osteoarthritis: Further results from the PRevention of knee Osteoarthritis in Overweight Females (PROOF) study. AB - BACKGROUND AND OBJECTIVES: The PRevention of knee Osteoarthritis in Overweight Females (PROOF) study (ISRCTN 42823086) described a trend for a decrease in the incidence of knee osteoarthritis (OA) by a tailored diet and exercise program (DEP) or by oral glucosamine sulfate in women at risk for the disease, using a composite clinical and/or radiological outcome. The aim of this updated post-hoc analysis was to re-assess the results according to more precise techniques and take advantage of the 2*2 factorial design. METHODS: A total of 407 overweight (BMI >= 27kg/m(2)) women of 50-60 years of age with no diagnosis of knee OA were randomized to: (1) no DEP + placebo (Control, N = 102), (2) DEP + placebo (DEP, N = 101), (3) glucosamine sulfate + no DEP (GS, N = 102), and (4) DEP + glucosamine sulfate (DEP + GS, N =102) and followed for 2.5 years, with standardized postero anterior, semiflexed (MTP) view knee radiographs at baseline and end of the study. DEP consisted of a tailored low fat and/or low caloric diet and easy to implement physical activities. Glucosamine was given as oral crystalline glucosamine sulfate 1500mg once daily, double-blinded vs. placebo. Incident knee OA was defined as radiographic progression of >=1mm minimum joint space narrowing (mJSN) in the medial tibiofemoral compartment, as previously assessed by the visual (manual) technique and by a new semi-automated method. Logistic regression analysis was used to calculate the odds ratio for the effect of the interventions. RESULTS: After 2.5 years, 11.8% of control subjects developed knee OA. This incidence was decreased with glucosamine sulfate, either alone or in combination with the DEP, but not by the DEP alone. Since there was no statistical interaction between treatments, the 2*2 factorial design allowed analysis of patients receiving glucosamine sulfate (N = 204) vs. those not receiving it (N = 203), similarly for those on the DEP (N = 203) or not (N = 204). Glucosamine sulfate significantly decreased the risk of developing knee OA: odds ratio (OR) = 0.41 (95% CI: 0.20-0.85, P = 0.02) by the manual JSN assessment method and OR = 0.42 (95% CI: 0.20-0.92, P = 0.03) by the semi-automated technique. Conversely, there was no decrease in risk with the DEP. CONCLUSIONS: Glucosamine sulfate decreased the risk of developing radiographic knee OA over 2.5 years in overweight, middle-aged women at risk, as determined by medial mJSN progression. Conversely a tailored diet and exercise program exerted no preventive effect, possibly because of the lower than expected effect on weight loss. PMID- 26806187 TI - Efficacy and safety of glucosamine sulfate in the management of osteoarthritis: Evidence from real-life setting trials and surveys. AB - The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm recommends chronic symptomatic slow acting drugs for osteoarthritis (SYSADOAs) including glucosamine sulfate (GS) and chondroitin sulfate (CS) as first-line therapy for knee osteoarthritis (OA). Numerous studies are published on the use of SYSADOAs in OA; however, the efficacy of this class is still called into question largely due to the regulatory status, labeling and availability of these medications which differ substantially across the world. Examination of the evidence for the prescription patented crystalline GS (pCGS) formulation at a dose of 1500mg once-daily demonstrates superiority over other GS and glucosamine hydrochloride (GH) formulations and dosage regimens. Thus, the ESCEO task force advocates differentiation of prescription pCGS over other glucosamine preparations. Long term clinical trials and real-life studies show that pCGS may delay joint structural changes, suggesting potential benefit beyond symptom control when used early in the management of knee OA. Real-life pharmacoeconomic studies demonstrate a long-term reduction in the need for additional pain analgesia and non-steroidal anti-inflammatory drugs (NSAIDs) with pCGS, with a significant reduction of over 50% in costs associated with medications, healthcare consultations and examinations over 12 months. Furthermore, treatment with pCGS for at least 12 months leads to a reduction in the need for total joint replacement for at least 5 years following treatment cessation. Thus, pCGS (1500mg od) is a logical choice to maximize clinical benefit in OA patients, with demonstrated medium-term control of pain and lasting impact on disease progression. PMID- 26806188 TI - A consensus statement on the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis-From evidence-based medicine to the real-life setting. AB - The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) published a treatment algorithm for the management of knee osteoarthritis (OA) in 2014, which provides practical guidance for the prioritization of interventions. Further analysis of real-world data for OA provides additional evidence in support of pharmacological interventions, in terms of management of OA pain and function, avoidance of adverse events, disease modifying effects and long-term outcomes, e.g., delay of total joint replacement surgery, and pharmacoeconomic factors such as reduction in healthcare resource utilization. This article provides an updated assessment of the literature for selected interventions in OA, focusing on real-life data, with the aim of providing easy-to-follow advice on how to establish a treatment flow in patients with knee OA in primary care clinical practice, in support of the clinicians' individualized assessment of the patient. In step 1, background maintenance therapy with symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) is recommended, for which high-quality evidence is provided only for the prescription formulations of patented crystalline glucosamine sulfate and chondroitin sulfate. Paracetamol may be added for rescue analgesia only, due to limited efficacy and increasing safety signals. Topical non-steroidal anti inflammatory drugs (NSAIDs) may provide additional symptomatic treatment with the same degree of efficacy as oral NSAIDs without the systemic safety concerns. Oral NSAIDs maintain a central role in step 2 advanced management of persistent symptoms. However, oral NSAIDs are highly heterogeneous in terms of gastrointestinal and cardiovascular safety profile, and patient stratification with careful treatment selection is advocated to maximize the risk:benefit ratio. Intra-articular hyaluronic acid as a next step provides sustained clinical benefit with effects lasting up to 6 months after a short-course of weekly injections. As a last step before surgery, the slow titration of sustained release tramadol, a weak opioid, affords sustained analgesia with improved tolerability. PMID- 26806189 TI - Efficacy and safety of topical NSAIDs in the management of osteoarthritis: Evidence from real-life setting trials and surveys. AB - Topical non-steroidal anti-inflammatory drugs (NSAIDs) are recommended in international and national guidelines as an early treatment option for the symptomatic management of knee and hand osteoarthritis (OA), and may be used ahead of oral NSAIDs due to their superior safety profile. The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm recommends topical NSAIDs for knee OA in addition to the pharmacological background of symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) and rescue analgesia with paracetamol and non-pharmacological treatment, if the patient is still symptomatic. Topical NSAIDs have a moderate effect on pain relief, with efficacy similar to that of oral NSAIDs, with the advantage of a better risk:benefit ratio. In real-life studies, topical and oral NSAIDs demonstrate an equivalent effect on knee pain over 1 year of treatment, with fewer adverse events due to lower systemic absorption of topical NSAIDs compared with oral NSAIDs. As a result, topical NSAIDs may be the preferred treatment option, especially in OA patients aged >=75 years, and those with co morbidities or at an increased risk of cardiovascular, gastrointestinal, or renal side effects. Furthermore, using topical NSAIDs in inflammatory rheumatic diseases leads to a 40% reduction in the need for concomitant oral NSAIDs. When selecting a topical NSAID, absorption and bioavailability are important because of heterogeneity among topical drug formulations. Molecules like etofenamate have a bioavailability of >20% and evidence for accumulation in synovial tissues, with efficacy demonstrated as improvement in pain and function in real-life studies of OA patients. Diclofenac also shows good efficacy alongside evidence that diclofenac accumulates in the synovium. PMID- 26806190 TI - Effect of Water Adsorption on Carrier Trapping Dynamics at the Surface of Anatase TiO2 Nanoparticles. AB - Charge carrier trapping plays a vital role in heterogeneous photocatalytic water splitting because it strongly affects the dynamics of photogenerated charges and hence the photoconversion efficiency. Although hole trapping by water at water/photocatalyst interface is the first step of oxygen evolution in water splitting, little has been known on how water adsorbate itself is involved in hole trapping dynamics. To clarify this point, we have performed infrared transient and steady-state absorption spectroscopy of anatase TiO2 nanoparticles as a function of the number of water adsorbate layers. Here, we demonstrate that water molecules reversibly adsorbed in the first layer on TiO2 nanoparticles are capable to trap photogenerated holes, while water in the second layer hydrogen bonding to the first-layer water makes hole trapping less effective. PMID- 26806192 TI - Ultrasonographic features and clinical characteristics of Warthin-like variant of papillary thyroid carcinoma. AB - Warthin-like variant of papillary thyroid carcinoma (WVPTC) is a rare entity recently characterized. We evaluated ultrasonographic (US) features and clinical characteristics of WVPTC. Nine patients were diagnosed with WVPTC through surgery in our institution from May 2005 to January 2015. Eight of nine patients had available preoperative US images. A retrospective review of the US and clinical characteristics was performed. WVPTC compromised of 0.06% of 14,071 PTCs surgically confirmed. A mean age of nine patients was 53.2 years (range, 32-75 years). The mean nodule size of nine WVPTCs was 0.9 cm (range, 0.5-1.5 cm). Two patients showed central nodal metastasis and one patient with conventional PTC as an index tumor underwent central and lateral neck dissection. No one showed recurrence or distant metastasis during the follow-up period (mean, 4.6 years; range, 0.6-10 years). The most common US features of WVPTCs were solid composition (62.5%), hypoechogenicity (75%), and wider-than-tall shape (100%), respectively. Four (50%) of eight nodules showed well-defined margin and three (37.5%) of them had cystic component. One of eight resembled focal thyroiditis. Three nodules were considered as probably benign with US. All nine cases demonstrated underlying heterogeneous parenchymal echogenicity and accompanied chronic lymphocytic thyroiditis in permanent sections. Thyroid function tests in all patients were normal except for one with subclinical hypothyroidism. WVPTC is an uncommon subtype of PTC and has favorable prognosis, which can be misdiagnosed as a probably benign nodule or focal thyroiditis with US. All cases are associated with heterogeneous parenchyma in the background. PMID- 26806193 TI - Fibroblast growth factor 1 levels are elevated in newly diagnosed type 2 diabetes compared to normal glucose tolerance controls. AB - Fibroblast growth factor 1 (FGF1) has been recently characterized as a potent insulin sensitizer that regulates adipose tissue remodeling, but the physiological role of FGF1 remains unclear. This study measured serum FGF1 levels for the first time in patients with newly diagnosed type 2 diabetes mellitus (T2DM), and further explored the correlations between FGF1 levels and various metabolic parameters in T2DM. Serum FGF1 levels were determined using ELISA in age-, sex- and BMI- matched subjects with normal glucose tolerance (NGT) (n=80) and newly diagnosed T2DM (n=80). Oral glucose tolerance test (OGTT), glycosylated hemoglobin (HbA1C), blood lipids, and insulin secretion were also measured. Insulin resistance and pancreatic beta-cell function were assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta cell function (HOMA-beta), respectively. Serum FGF1 levels were significantly higher in T2DM patients than in normal glucose tolerance subjects (74.52 [55.91~101.34] vs. 60.31 [48.99~83.91] pg/mL; P<0.05). In addition, serum FGF1 level positively correlated with body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), fasting plasma glucose (FPG), 2-h post-OGTT glucose (2h PG), and HbA1C (all P values <0.05) in T2DM subjects. Multivariate regression analyses showed that BMI and HbA1C were the independent factors influencing serum FGF1 levels. Logistic regression analyses demonstrated that serum FGF1 was significantly associated with type 2 diabetes (P<0.01). Circulating concentrations of FGF1 are significantly increased in T2DM patients. Our results suggest that FGF1 may play a role in the pathogenesis of T2DM. PMID- 26806194 TI - Methods of mesophyll conductance estimation: its impact on key biochemical parameters and photosynthetic limitations in phosphorus-stressed soybean across CO2. AB - Despite the development of various methods, the rapid estimation of mesophyll conductance (gm ) for a large number of samples is still a daunting challenge. Although the accurate estimation of gm is critical to partition photosynthetic limitations by stomatal (Ls ) and mesophyll (Lm ) conductance and by photo biochemical (Lb ) processes, the impact of various gm estimation methods on this is ambiguous. As phosphorus (P) starvation and elevated CO2 (eCO2 ) strongly affect photosynthetic processes, their combined effect on the proportional changes in these limitations are not well understood. To investigate this, while also evaluating distinct recent methods of gm estimation sharing few common theories and assumptions, soybean was grown under a range of P nutrition at ambient and eCO2 . Methods significantly affected gm and carboxylation efficiency (VCmax ) but not other photosynthetic parameters. In all the methods, all photosynthetic parameters responded similarly to treatments. However, the percentage difference between VCmax assuming finite and infinite gm was highly inconsistent among methods. The primary mechanism responsible for P limitation to soybean photosynthesis was not CO2 diffusion limitations but Lb comprised of reduced chlorophyll, photochemistry and biochemical processes. The eCO2 decreased Lb but increased Lm without affecting Ls across leaf P concentration. Although each method explored advances of our understanding about gm variability, they all require assumptions of varying degrees, which lead to the discrepancy in the gm values. Among the methods, the oxygen sensitivity-based gm estimation appeared to be suitable for the quick assessment of a large number of samples or genotypes. Digital tools are provided for the easy estimation of gm for some methods. PMID- 26806195 TI - [Improving secondary hyperparathyroidism treatment in Maghreb to get rid of brown tumors]. PMID- 26806196 TI - Comparisons of the transferability of plasmids pCAR1, pB10, R388, and NAH7 among Pseudomonas putida at different cell densities. AB - The transferability of plasmids pCAR1, pB10, R388, and NAH7 was compared using the same donor-recipient system at different cell density combinations in liquid or on a solid surface. pCAR1 was efficiently transferred in liquid, whereas the other plasmids were preferentially transferred on a solid surface. Difference of liquid or solid affected the transfer frequency especially at lower cell densities. PMID- 26806197 TI - Quantitation of Thioprolines in Grape Wine by Isotope Dilution-Liquid Chromatography-Tandem Mass Spectrometry. AB - Cysteine reacts with reactive carbonyls to form thioprolines, which have been demonstrated to possess various pharmaceutical properties. Therefore, thioproline formation is considered as a major detoxification pathway for carcinogenic reactive carbonyls. In this study, we report the initial identification of thiazolidine-4-carboxylic acid (1) and 2-methylthiazolidine-4-carboxylic acid (2), two very common thioprolines, formed by reacting formaldehyde and acetaldehyde with cysteine in grape wine samples. We have developed an isotope dilution-liquid chromatography-tandem mass spectrometry method featuring high sensitivity (limit of detection of <=1.5 ng/mL) and selectivity to quantitate compounds 1 and 2. The method after validated to be highly accurate (recovery of >=92%) and precise [intraday relative standard deviation (RSD) of <=4.1% and interday RSD of <=9.7%] was applied to determine the varying compound 1 and 2 contents in grape wine samples. Results revealed the grape type and storage duration-dependent formation of thioprolines in grape wines. Overall, the results are expected to facilitate compound-dependent investigations of the health benefits of grape wine, and our findings could be adopted to predict the age of grape wine. PMID- 26806199 TI - High resolution triple resonance micro magic angle spinning NMR spectroscopy of nanoliter sample volumes. AB - To be able to study mass-limited samples and small single crystals, a triple resonance micro-magic angle spinning (MUMAS) probehead for the application of high-resolution solid-state NMR of nanoliter samples was developed. Due to its excellent rf performance this allows us to explore the limits of proton NMR resolution in strongly coupled solids. Using homonuclear decoupling we obtain unprecedented (1)H linewidths for a single crystal of glycine (Deltanu(CH2) = 0.14 ppm) at high field (20 T) in a directly detected spectrum. The triple channel design allowed the recording of high-resolution MUMAS (13)C-(15)N correlations of [U-(13)C-(15)N] arginine HCl and shows that the superior (1)H resolution opens the way for high-sensitivity inverse detection of heteronuclei even at moderate spinning speeds and rf-fields. Efficient decoupling leads to long coherence times which can be exploited in many correlation experiments. PMID- 26806198 TI - Proteomic profiling of dextran sulfate sodium induced acute ulcerative colitis mice serum exosomes and their immunomodulatory impact on macrophages. AB - Macrophages are essential for the maintenance of intestinal homeostasis, and their activation has been proposed to be critical to the pathogenesis of inflammatory bowel disease (IBD). Although there are many recognized mediators of macrophage activation, increasing evidence suggests that macrophages respond to exosome stimulation. Exosomes are 40-150 nm microvesicles released from different cell types and are found in a variety of physiological fluids, including serum. As studies have shown that circulating exosomes participate in intercellular communication and can mediate the immune response, we hypothesized that exosomes may play a role in the pathogenesis of IBD though modulation of macrophage activity. In this study, we used the dextran sulfate sodium (DSS) induced acute colitis mice model to investigate the effect of serum exosomes on macrophages and identify exosome proteins potentially involved in macrophage activation. We treated RAW264.7 macrophages with serum exosomes isolated from dextran sulfate sodium induced mice and found that treatment induced phosphorylation of p38 and ERK and production of tumor necrosis factor alpha when compared to treatment with exosomes isolated from control mice. Subsequent proteomic analysis identified 56 differentially expressed proteins, a majority of which were acute-phase proteins and immunoglobulins. Bioinformatics analysis suggested these proteins were mainly involved in the complement and coagulation cascade, which has been implicated in macrophage activation. Our findings provide new insight into the role of circulating serum exosomes in acute colitis and contribute to the understanding of macrophage activation in the pathogenesis of IBD. PMID- 26806200 TI - Inhibition of malaria parasite Plasmodium falciparum development by crotamine, a cell penetrating peptide from the snake venom. AB - We show here that crotamine, a polypeptide from the South American rattlesnake venom with cell penetrating and selective anti-fungal and anti-tumoral properties, presents a potent anti-plasmodial activity in culture. Crotamine inhibits the development of the Plasmodium falciparum parasites in a dose dependent manner [IC50 value of 1.87 MUM], and confocal microscopy analysis showed a selective internalization of fluorescent-labeled crotamine into P. falciparum infected erythrocytes, with no detectable fluorescence in uninfected healthy erythrocytes. In addition, similarly to the crotamine cytotoxic effects, the mechanism underlying the anti-plasmodial activity may involve the disruption of parasite acidic compartments H(+) homeostasis. In fact, crotamine promoted a reduction of parasites organelle fluorescence loaded with the lysosomotropic fluorochrome acridine orange, in the same way as previously observed mammalian tumoral cells. Taken together, we show for the first time crotamine not only compromised the metabolism of the P. falciparum, but this toxin also inhibited the parasite growth. Therefore, we suggest this snake polypeptide as a promising lead molecule for the development of potential new molecules, namely peptidomimetics, with selectivity for infected erythrocytes and ability to inhibit the malaria infection by its natural affinity for acid vesicles. PMID- 26806201 TI - Hypercoagulation and hyperkinetic blood pressure indicative of physiological loss of-control despite behavioural control in Africans: The SABPA study. AB - OBJECTIVES: A dissociation between behavioural (in-control) and physiological parameters (indicating loss-of-control) is associated with cardiovascular risk in defensive coping (DefS) Africans. We evaluated relationships between DefS, sub clinical atherosclerosis, low-grade inflammation and hypercoagulation in a bi ethnic sex cohort. METHODS: Black (Africans) and white Africans (Caucasians) (n = 375; aged 44.6 +/- 9.7 years) were included. Ambulatory BP, vascular structure (left carotid cross-sectional wall area (L-CSWA) and plaque counts), and markers of coagulation and inflammation were quantified. Ethnicity/coping style interaction was revealed only in DefS participants. RESULTS: A hypertensive state, less plaque, low-grade inflammation, and hypercoagulation were more prevalent in DefS Africans (27-84%) than DefS Caucasians (18-41%). Regression analyses demonstrated associations between L-CSWA and 24 hour systolic BP (R(2) = 0.38; beta = 0.78; p < 0.05) in DefS African men but not in DefS African women or Caucasians. No associations between L-CSWA and coagulation markers were evident. CONCLUSION: Novel findings revealed hypercoagulation, low-grade inflammation and hyperkinetic BP (physiological loss-of-control responses) in DefS African men. Coupled to a self-reported in-control DefS behavioural profile, this reflects dissociation between behaviour and physiology. It may explain changes in vascular structure, increasing cerebrovascular disease risk in a state of hyper-vigilant coping. PMID- 26806203 TI - Infantile Systemic Hyalinosis with Mutation in ANTXR2. PMID- 26806204 TI - Isolated Multiple Subepicardiac and Epicardiac Echinococcosis. PMID- 26806205 TI - Kawasaki Disease in a 2-year-old Child with Dengue Fever: Correspondence. PMID- 26806206 TI - Kawasaki Disease in a 2-year-old Child with Dengue Fever: Author's Reply. PMID- 26806208 TI - Blood Group Change in Pediatric Leukemia: A Rare Phenomena. PMID- 26806207 TI - Succinic Semialdehyde Dehydrogenase Deficiency Presenting as Autism Spectrum Disorder. PMID- 26806209 TI - Effect of the industrial canning on the toxicity of mussels contaminated with diarrhetic shellfish poisoning (DSP) toxins. AB - The effect of canning in pickled sauce and autoclaving on weight, toxin content, toxin concentration and toxicity of steamed mussels was studied. Weight decreased by 25.5%. Okadaic acid (OA) and DTX2 content of mussel meat decreased by 24.1 and 42.5%, respectively. The estimated toxicity of the mussel remained nearly unchanged (increased by 2.9%). A part of the toxins lost by the mussels was leached to the sauce but the remaining part should have been thermally degraded. DTX2 underwent more degradation than OA and, in both toxins, free forms more than conjugated ones. This process, therefore, cannot be responsible for the large increments of toxicity of processed mussels -relative to the raw ones-sometimes detected by food processing companies. The final product could be monitored in several ways, but analysing the whole can content or the mussel meat once rehydrated seems to be the most equivalents to the raw mussel controls. PMID- 26806210 TI - Proteomic and Real-Time PCR analyses of Saccharomyces cerevisiae VL3 exposed to microcystin-LR reveals a set of protein alterations transversal to several eukaryotic models. AB - Some of the most common toxins present in freshwater, in particular microcystins (MCs), are produced by cyanobacteria. These toxins have a negative impact on human health, being associated with episodes of acute hepatotoxicity and being considered potentially carcinogenic to humans. To date the exact mechanisms of MC induced toxicity and tumor promotion were not completely elucidated. To get new insights underlying microcystin-LR (MCLR) molecular mechanisms of toxicity we have performed the proteomic profiling using two-dimensional electrophoresis and MALDI-TOF/TOF of Saccharomyces cerevisiae cells exposed for 4 h-1 nM and 1 MUM of MCLR, and compared them to the control (cells not exposed to MCLR). We identified 14 differentially expressed proteins. The identified proteins are involved in metabolism, genotoxicity, cytotoxicity and stress response. Furthermore, we evaluated the relative expression of yeast's PP1 and PP2A genes and also of genes from the Base Excision Repair (BER) DNA-repair system, and observed that three out of the five genes analyzed displayed dose-dependent responses. Overall, the different proteins and genes affected are related to oxidative stress and apoptosis, thus reinforcing that it is probably the main mechanism of MCLR toxicity transversal to several organisms, especially at lower doses. Notwithstanding these MCLR responsive proteins could be object of further studies to evaluate their suitability as biomarkers of exposure to the toxin. PMID- 26806211 TI - Structural and evolutionary insights into endogenous alpha-phospholipase A2 inhibitors of Latin American pit vipers. AB - Phospholipases A2 are major components of snake venoms (svPLA2s) and are able to induce multiple local and systemic deleterious effects upon envenomation. Several snake species are provided with svPLA2 inhibitors (sbPLIs) in their circulating blood, which confer a natural resistance against the toxic components of homologous and heterologous venoms. The sbPLIs belong to any of three structural classes named alpha, beta and gamma. In the present study, we identified, characterized and performed structural and evolutionary analyses of sbalphaPLIs transcripts and the encoded proteins, in the most common Latin American pit vipers belonging to Crotalus, Bothrops and Lachesis genera. Mutation data indicated that sbalphaPLIs from Latin American snakes might have evolved in an accelerated manner, similarly to that reported for sbalphaPLIs from Asian snakes, and possibly co-evoluted with svPLA2s in response to the diversity of target enzymes. The importance of sbalphaPLI trimerization for the effective binding and inhibition of acidic svPLA2s is discussed and conserved cationic residues located at the central pore of the inhibitor trimer are suggested to be a significant part of the binding site of sbalphaPLIs to acidic svPLA2s. Our data contribute to the current body of knowledge on the structural and evolutionary characteristics of sbPLIs, in general, and may assist in the future development of selective inhibitors for secretory PLA2 from several sources. PMID- 26806212 TI - Cyclophosphamide in dermatology. AB - Cyclophosphamide is a chemotherapeutic agent which was first discovered in experimental tumours in rats, and it has since been widely used to treat malignancies and severe manifestations of various auto-immune diseases. High-dose chemotherapy and continuous daily oral regimens are associated with significant toxicity profiles, but i.v. pulsed regimens have lowered the rates of adverse effects in rheumatological studies. Cyclophosphamide has been shown to be useful in the treatment of severe autoimmune conditions due to its powerful immunosuppressive ability; however, it remains a relatively underused modality in dermatology. This article reviews the current literature on cyclophosphamide and its clinical applications in dermatology. PMID- 26806214 TI - Hunting for Monolayer Oxide Nanosheets and Their Architectures. AB - In two-dimensional materials, thickness identification with a sufficient characterization range is essential to fundamental study and practical applications. Here, we report a universal optical method for rapid and reliable identification of single- to quindecuple-layers in oxide nanosheets (Ti0.87O2, Ca2Nb3O10, Ca2NaNb4O13). Because of their wide bandgap nature (Eg = ~4 eV) and zero opacity, most oxide nanosheets exhibit a weak white-light contrast (<1.5%), which precludes optical identification. Through a systematic study of the optical reflectivity of Ti0.87O2 nanosheets on SiO2/Si substrates, we show that the use of thinner SiO2 (~100 nm) offers optimum visualization conditions with a contrast of >5%; the contrast is a nonmonotonic function of wavelength and changes its sign at ~550 nm; the nanosheets are brighter than the substrate at short wavelengths and darker at long ones. Such a nonmonotonic optical response is common to semiconducting oxide nanosheets, including Ca2Nb3O10 and Ca2NaNb4O13. The optical contrast differences between the substrates and nanosheets with different numbers of layers were collected, serving as a standard reference from which the number of layers can be determined by optical microscopy. Our method will facilitate the thickness-dependent study of various oxide nanosheets and their architectures, as well as expedite research toward practical applications. PMID- 26806213 TI - Controlled growth of CH3NH3PbI3 nanowires in arrays of open nanofluidic channels. AB - Spatial positioning of nanocrystal building blocks on a solid surface is a prerequisite for assembling individual nanoparticles into functional devices. Here, we report on the graphoepitaxial liquid-solid growth of nanowires of the photovoltaic compound CH3NH3PbI3 in open nanofluidic channels. The guided growth, visualized in real-time with a simple optical microscope, undergoes through a metastable solvatomorph formation in polar aprotic solvents. The presently discovered crystallization leads to the fabrication of mm(2)-sized surfaces composed of perovskite nanowires having controlled sizes, cross-sectional shapes, aspect ratios and orientation which have not been achieved thus far by other deposition methods. The automation of this general strategy paves the way towards fabrication of wafer-scale perovskite nanowire thin films well-suited for various optoelectronic devices, e.g. solar cells, lasers, light-emitting diodes and photodetectors. PMID- 26806215 TI - All-photonic drying and sintering process via flash white light combined with deep-UV and near-infrared irradiation for highly conductive copper nano-ink. AB - We developed an ultra-high speed photonic sintering method involving flash white light (FWL) combined with near infrared (NIR) and deep UV light irradiation to produce highly conductive copper nano-ink film. Flash white light irradiation energy and the power of NIR/deep UV were optimized to obtain high conductivity Cu films. Several microscopic and spectroscopic characterization techniques such as scanning electron microscopy (SEM), a x-ray diffraction (XRD), and Fourier transform infrared (FT-IR) spectroscopy were employed to characterize the Cu nano films. Optimally sintered Cu nano-ink films produced using a deep UV-assisted flash white light sintering technique had the lowest resistivity (7.62 MUOmega.cm), which was only 4.5-fold higher than that of bulk Cu film (1.68 MUOmega*cm). PMID- 26806216 TI - Non-motor symptoms in patients with hereditary spastic paraplegia caused by SPG4 mutations. AB - BACKGROUND AND PURPOSE: Non-motor manifestations are frequently overlooked in degenerative disorders and little is known about their frequency and clinical relevance in SPG4 hereditary spastic paraplegia (SPG4-HSP). METHODS: Thirty patients with SPG4-HSP and 30 healthy controls answered the Modified Fatigue Impact Scale, Epworth Sleepiness Scale, Brief Pain Inventory and Beck Depression Inventory. Student's t test was used to compare groups and linear regression was used to assess correlations. RESULTS: Patients had higher fatigue scores than controls (31.0 +/- 16.5 vs. 14.5 +/- 16.0, P = 0.002) as well as pain (3.4 +/- 2.7 vs. 1.0 +/- 1.6, P = 0.001) and depression (12.7 +/- 8.9 vs. 4.4 +/- 3.8, P < 0.001, respectively). Fatigue was associated with depression and possibly with disease severity (P = 0.008 and 0.07, respectively). CONCLUSIONS: Fatigue, pain and depression are frequent and often severe manifestations in patients with SPG4 HSP. PMID- 26806217 TI - Daclizumab high-yield process reduced the evolution of new gadolinium-enhancing lesions to T1 black holes in patients with relapsing-remitting multiple sclerosis. AB - BACKGROUND AND PURPOSE: In the SELECT study, treatment with daclizumab high-yield process (DAC HYP) versus placebo reduced the frequency of gadolinium-enhancing (Gd(+) ) lesions in patients with relapsing-remitting multiple sclerosis (RRMS). The objective of this post hoc analysis of SELECT was to evaluate the effect of DAC HYP on the evolution of new Gd(+) lesions to T1 hypointense lesions (T1 black holes). METHODS: SELECT was a randomized double-blind study of subcutaneous DAC HYP 150 or 300 mg or placebo every 4 weeks. Magnetic resonance imaging (MRI) scans were performed at baseline and weeks 24, 36 and 52 in all patients and monthly between weeks 4 and 20 in a subset of patients. MRI scans were evaluated for new Gd(+) lesions that evolved to T1 black holes at week 52. Data for the DAC HYP groups were pooled for analysis. RESULTS: Daclizumab high-yield process reduced the number of new Gd(+) lesions present at week 24 (P = 0.005) or between weeks 4 and 20 (P = 0.014) that evolved into T1 black holes at week 52 versus placebo. DAC HYP treatment also reduced the percentage of patients with Gd(+) lesions evolving to T1 black holes versus placebo. CONCLUSIONS: Treatment with DAC HYP reduced the evolution of Gd(+) lesions to T1 black holes versus placebo, suggesting that inflammatory lesions that evolved during DAC HYP treatment are less destructive than those evolving during placebo treatment. PMID- 26806218 TI - Amyotrophic lateral sclerosis causes small fiber pathology. AB - BACKGROUND AND PURPOSE: Our aim was to address the correlation between small fiber loss and amyotrophic lateral sclerosis (ALS) for disease onset, phenotype, genotype, duration, severity and sensory findings. METHODS: Consecutive patients referred for suspected ALS were screened. Exclusion criteria were possible ALS and previous diagnosis or known risk factors for small fiber neuropathies. A sural nerve conduction study (NCS) was bilaterally recorded. The ALS functional rating scale revised was administered and loss of functions were calculated using the Milano-Torino staging (MITOS) system. Sensory symptoms and signs were recorded. Genetic analysis was performed by the next-generation sequencing approach. Skin biopsy was performed at the distal leg and intraepidermal nerve fiber (IENF) density was quantified in three non-consecutive sections following published guidelines. Findings were referred to age- and sex-adjusted normative values. RESULTS: Fifty-seven patients including six with facial onset sensory and motor neuronopathy (FOSMN) were enrolled. Eight (15.7%) pure ALS patients and five (83%) FOSMN patients complained of sensory disturbances with different distributions. Sural NCS was normal in all except two patients. IENF density was reduced in 75.4% of pure ALS and 50% of FOSMN patients, without correlation with any disease features. IENF density was similarly reduced in bulbar (78.5%), flail limb (87.5%), pyramidal (100%), and spinal (68.2%) onset, as well as in genetic (83.3%) and sporadic (82%) ALS. There was no correlation with genotype, disease duration and severity. CONCLUSIONS: Intraepidermal nerve fiber loss is a feature of most ALS patients. It does not correlate with onset, phenotype, course and severity of the disease, and cannot be considered a clinical or prognostic biomarker. PMID- 26806219 TI - A large silent cysticercus occupying most of the medulla oblongata. PMID- 26806220 TI - Controversies about irreversible loss of brain functions and cerebral perfusion in brain death. PMID- 26806221 TI - Type 2 diabetes and amyotrophic lateral sclerosis. PMID- 26806226 TI - Quantifying the Electrocatalytic Turnover of Vitamin B12-Mediated Dehalogenation on Single Soft Nanoparticles. AB - We report the electrocatalytic dehalogenation of trichloroethylene (TCE) by single soft nanoparticles in the form of Vitamin B12 -containing droplets. We quantify the turnover number of the catalytic reaction at the single soft nanoparticle level. The kinetic data shows that the binding of TCE with the electro-reduced vitamin in the Co(I) oxidation state is chemically reversible. PMID- 26806224 TI - Super-resolution microscopy as a potential approach to diagnosis of platelet granule disorders. AB - BACKGROUND: Many platelet functions are dependent on bioactive molecules released from their granules. Deficiencies of these granules in number, shape or content are associated with bleeding. The small size of these granules is such that imaging them for diagnosis has traditionally required electron microscopy. However, recently developed super-resolution microscopes provide sufficient spatial resolution to effectively image platelet granules. When combined with automated image analysis, these methods provide a quantitative, unbiased, rapidly acquired dataset that can readily and reliably reveal differences in platelet granules between individuals. OBJECTIVE: To demonstrate the ability of structured illumination microscopy (SIM) to efficiently differentiate between healthy volunteers and three patients with Hermansky-Pudlak syndrome. METHODS: Blood samples were taken from three patients with Hermansky-Pudlak syndrome and seven controls. Patients 1-3 have gene defects in HPS1, HPS6 and HPS5, respectively; all controls were healthy volunteers. Platelet-rich plasma was isolated from blood and the platelets fixed, stained for CD63 and processed for analysis by immunofluorescence microscopy, using a custom-built SIM microscope. RESULTS: SIM can successfully resolve CD63-positive structures in fixed platelets. A determination of the number of CD63-positive structures per platelet allowed us to conclude that each patient was significantly different from all of the controls with 99% confidence. CONCLUSIONS: A super-resolution imaging approach is effective and rapid in objectively differentiating between patients with a platelet bleeding disorder and healthy volunteers. CD63 is a useful marker for predicting Hermansky-Pudlak syndrome and could be used in the diagnosis of patients suspected of other platelet granule disorders. PMID- 26806227 TI - Corrigendum. PMID- 26806228 TI - Optimising the diagnostic strategy for onychomycosis from sample collection to FUNGAL identification evaluation of a diagnostic kit for real-time PCR. AB - Onychomycosis is a common nail disorder mainly due to dermatophytes for which the conventional diagnosis requires direct microscopic observation and culture of a biological sample. Nevertheless, antifungal treatments are commonly prescribed without a mycological examination having been performed, partly because of the slow growth of dermatophytes. Therefore, molecular biology has been applied to this pathology, to support a quick and accurate distinction between onychomycosis and other nail damage. Commercial kits are now available from several companies for improving traditional microbiological diagnosis. In this paper, we present the first evaluation of the real-time PCR kit marketed by Bio Evolution for the diagnosis of dermatophytosis. Secondly, we compare the efficacy of the kit on optimal and non-optimal samples. This study was conducted on 180 nails samples, processed by conventional methods and retrospectively analysed using this kit. According to our results, this molecular kit has shown high specificity and sensitivity in detecting dermatophytes, regardless of sample quality. On the other hand, and as expected, optimal samples allowed the identification of a higher number of dermatophytes by conventional mycological diagnosis, compared to non-optimal samples. Finally, we have suggested several strategies for the practical use of such a kit in a medical laboratory for quick pathogen detection. PMID- 26806230 TI - Physical Activity Improves Borderline Ankle-Brachial Index Values in a Cardiovascular Risk Population. AB - BACKGROUND: Peripheral arterial disease (PAD) is an underdiagnosed and undertreated disease because it remains asymptomatic for so long. The ankle brachial index (ABI) is a valid method for detecting PAD in lower extremities. ABI <=0.90 indicates incident PAD. Recent studies have found that subjects with borderline ABI values (0.91-1.00) have increased mortality rates. The objective of our 7-year follow-up study was to investigate the progression of PAD in borderline ABI subjects, who underwent a multifactorial cardiovascular intervention. METHODS: A total of 193 subjects with borderline ABI were examined in 2005-2006. None of them had previously diagnosed diabetes, cardiovascular or renal disease or intermittent claudication. They were given conventional treatment for multiple risk factors of cardiovascular diseases (hypertension, hypercholesterolemia, elevated blood glucose, smoking, and overweight). Sixty four percent of these subjects (n = 123) attended a follow-up visit in 2012. RESULTS: Of the 123 subjects with borderline ABI (mean age 59.0 +/- 6.5 years, 62% female) at baseline, 18 (15%, 95% confidence intervals [CI]: 9%-22%) developed incident PAD during the follow-up. The mean ABI was 0.97 +/- 0.03 at baseline and 1.01 +/- 0.12 at 7-year follow-up visit. The change in mean ABI was +0.04 (95% CI: 0.03-0.07), P < 0.001. ABI improved significantly in 25 (20%) subjects. In multivariate ordered logistic regression analyses high and even moderate leisure-time physical activity (LTPA; odds ratio 6.15; 95% CI: 1.99 19.1) predicted a rise in ABI in comparison to low LTPA. CONCLUSIONS: Physical activity seems to improve significantly ABI values among men and women with borderline ABI (0.91-1.00). PMID- 26806229 TI - Caring for patients with rabies in developing countries - the neglected importance of palliative care. AB - Although limited publications address clinical management of symptomatic patients with rabies in intensive care units, the overwhelming majority of human rabies cases occur in the rural setting of developing countries where healthcare workers are few, lack training and drugs. Based on our experience, we suggest how clinicians in resource-limited settings can make best use of essential drugs to provide assistance to patients with rabies and their families, at no risk to themselves. Comprehensive and compassionate patient management of furious rabies should aim to alleviate thirst, anxiety and epileptic fits using infusions, diazepam or midazolam and antipyretic drugs via intravenous or intrarectal routes. Although the patient is dying, respiratory failure must be avoided especially if the family, after being informed, wish to take the patient home alive for funereal rites to be observed. Healthcare staff should be trained and clinical guidelines should be updated to include palliative care for rabies in endemic countries. PMID- 26806231 TI - Open Removal of Penetrating Inferior Vena Cava Filter with Repair of Secondary Aortic Dissection: Case Report. AB - Inferior vena cava (IVC) filters are indicated for the management of venous thromboembolism in patients who are not candidates for anticoagulation, have a contraindication to anticoagulation or who have recurrent thromboembolism despite anticoagulation. As IVC filter usage has increased, there has been a corresponding increase in presentation of filter-related complications. Filter leg penetration is commonly seen although is infrequently associated with complications. But in a small percentage of patients, penetration can result in damage to adjacent structures: duodenum, lumbar spine, and rarely the aorta. We report the case of a 77-year-old man with a chronic aortoiliac dissection secondary to aortic IVC filter penetration who underwent open filter retrieval and aortic repair. PMID- 26806232 TI - Complicated Fenestrated Endovascular Repair of a Pararenal Aortic Aneurysm. AB - We report the case of a 77-year-old man treated with a custom-made fenestrated endograft for pararenal aortic aneurysm repair. Fenestrations for the superior mesenteric and both the renal arteries and augmented anterior valley and/or scallop for the celiac trunk were performed. The procedure was complicated by the superior mesenteric artery stent-graft entrapment from the endograft delivery system release wires and total dislodgement into the endograft main body. Superior mesenteric artery restenting and displaced stent-graft removal completed the intervention. Fenestrated-endograft deployment should be performed by a team familiar with the device, deployment system, and bail out solutions. PMID- 26806233 TI - Endovascular Surgery, Open Surgery, and Primary Amputation in Nonagenarians Presenting with Critical Limb Ischemia. AB - BACKGROUND: The aim was to report the midterm outcome for nonagenarians with critical limb ischemia (CLI) and to identify factors affecting survival or limb salvage rates. METHODS: Nonagenarians who underwent endovascular surgery (ES), open surgery (OS), or primary amputation (PA) for CLI between 2005 and 2014 were included. Cox regression model identified factors affecting survival and limb salvage. RESULTS: ES was performed in 116 patients (119 limbs), OS in 73 patients (73 limbs), and PA in 54 patients (57 limbs). Mean follow-up was 10.38 months. There was no difference in survival between ES, OS, and PA groups: survival rate was 51.2% at 1 year and 38.9% at 2 years after ES, 48.3% at 1 year and 39.6% at 2 years after OS, and 50.6% at 1 years and 40.8% at 2 years after PA (P = 0.58). There was no difference in limb salvage between ES and OS groups: limb salvage rate was 88.2% and 77.8% at 1 and 2 years after ES and 87.3% and 77.6% at 1 and 2 years after OS. Coronary artery disease (hazard ratio [HR] 1.54; confidence interval [CI] 1.04-1.08; P = 0.01) was risk factor for death. Fully dependent state was risk factor for death (HR 4.2; CI 3.55-4.87; P < 0.001) and major amputation (HR 5.3; CI 1.32-1.67; P < 0.001). In fully dependent patients, 1-year and 2-year survival rate was 28.9% and 20.6%, respectively, and 1-year and 2-year limb salvage rate was 61.2% and 44.5%, respectively. CONCLUSIONS: With acceptable early and late mortality, limb salvage and maintenance of functional status and level of independent living, revascularization in nonagenarians is effective as long as the patient is not fully dependent. PMID- 26806234 TI - Acute Ischemia due to Superficial Femoral Artery Thrombosis: Results of In Situ Fibrinolysis. AB - BACKGROUND: The management of acute ischemia due to the thrombosis superficial femoral artery (SFA) stents is complex. In situ arterial fibrinolysis, still not evaluated in this indication, would allow, by lifting the ischemia and uncovering its cause, to avoid thrombectomy, endovascular recanalization, or arterial bypass. The purpose of the study was to evaluate the effectiveness, the complications, and the assisted secondary patency of in situ fibrinolysis for thrombosis of SFA stents. METHODS: We conducted a retrospective monocentric study with prospective collection of the data. Between October 2011 and December 2014, 86 in situ fibrinolysis procedures were carried out for acute lower limb ischemia. Twelve procedures were carried out for acute ischemia due to the thrombosis of SFA stents. Clinical success was defined by the lifting of acute ischemia. The causes of thromboses, the complications related to the fibrinolysis, and the secondary assisted patency were analyzed. RESULTS: The mean age of the patients was 66.3 (55-90) years. The average length of the stents was 119.3 (18-270) mm. In 10 patients, the thrombosis extended in the full length of the artery. The average time between the implantation of the stent and the initiation of the fibrinolysis was 180 (11-369) days. The average time between the beginning of the symptoms and fibrinolysis was 5 (0-12) days. The average duration of treatment was 46 (24-72) hr. Clinical success was obtained in all the patients. Diagnosed isolated or associated lesions were a progression of the atheromatous disease upstream or downstream of the stent in 6 cases, and an isolated intrastent restenosis in 3 cases. In 2 cases, no obvious cause was found. One or more additional endovascular procedures were carried out in 9 cases at the end of the fibrinolysis, and consisted of a transluminal intrastent angioplasty with an active balloon in 5 cases, an additional stenting in 3 cases, and the stenting of upstream or downstream arteries in 5 cases. Secondary assisted patency was 100% at 5 months. No major hemorrhagic complication was observed. Two false aneurysms at the site of femoral puncture were observed. CONCLUSION: Our results suggest that ischemia due to the thrombosis of SFA stents can be dealt with first intention in situ fibrinolysis which allows the endovascular treatment of the causal lesion, thus avoiding thrombectomy or bypass. PMID- 26806235 TI - Efficacy of Retrievable Inferior Vena Cava Filter Placement in the Prevention of Pulmonary Embolism during Catheter-Directed Thrombectomy for Proximal Lower Extremity Deep Vein Thrombosis. AB - BACKGROUND: Inferior vena cava (IVC) filter placement is not indicated for thrombolytic interventional treatment for deep vein thrombosis (DVT). We analyzed the efficacy and feasibility of retrievable IVC filter placement for the preventive management of embolic shedding during catheter-directed thrombectomy (CDT) for DVT of lower extremity. METHODS: Seventy patients (35 males and 35 females) who underwent retrievable IVC filter placement to prevent thrombus dislodgement during CDT in all symptomatic DVT with thrombus age suspected within 4 weeks of the lower extremity between March 2008 and January 2014 were included in this study. All patients underwent laboratory blood study, duplex ultrasound and/or computed tomography for diagnosis, treatment, and follow-up in accordance with treatment policy of our Uijeongbu St. Mary's hospital. Two types of retrievable IVC filters (OptEase Filter, Cordis, Roden, The Netherlands; Gunther Tulip Filter, Cook, Bloomington, IN) were used to prevent thromboembolic events during CDT. After filter placement, subcutaneous low-molecular-weight heparin and overlapped to warfarin or new oral anticoagulant tried to achieve a target international normalized ratio (INR) of 2.0-3.0 in warfarin patients. RESULTS: The thrombus was dislodged through the IVC filter during catheter-directed thrombolytic therapy in 22 patients (31.4%). In 22 cases, the thromboses were trapped by the retrievable IVC filter, and follow-up images showed thrombus capture. Thirty-four patients (48.6%) received percutaneous transluminal angioplasty (PTA). Additional stents were inserted in 23 patients (32.8%). Pulmonary embolism (PE) was not observed in patients implanted with retrievable IVC filters. CONCLUSIONS: Our study findings suggest that retrieval IVC filter placement during interventional treatments of DVT of lower extremity such as thrombectomy of vein thrombus with or without stent insertion at compressed deep vein is favorable and effective for protecting against PE or lethal complications. We recommend carefully that before the management of DVT thrombus of lower extremity, retrieval IVC filter placement should be considered for preventing morbidity related with the PE. PMID- 26806236 TI - What We Can Learn from Cases of Synchronous Acute Mesenteric Obstruction and Nonocclusive Mesenteric Ischemia: How to Reduce the Acute Mesenteric Ischemia Related Mortality Rate. AB - Although the survival rate of patients with ischemic heart disease has recently increased, it remains unknown why the mortality rate of acute mesenteric ischemia (AMI) remains high. Here, we report a possible method of improving the survival rate of patients with AMI obtained through 2 cases of simultaneous acute mesenteric obstruction (AMO) and nonocclusive mesenteric ischemia (NOMI). Case 1 was a 74-year-old woman with atrial fibrillation, hypertension, and dyslipidemia as underlying diseases who developed NOMI immediately after undergoing SMA thrombolysis. Case 2 was a 69-year-old man with atrial fibrillation, hypertension, chronic heart failure, chronic renal failure, and old myocardial infarction who was diagnosed with SMA occlusion complicated by NOMI on the basis of abdominal angiography findings during the first visit. Cure was achieved by thrombolytic therapy, resection of the necrotic intestine, and continuous intra arterial and/or intravenous injection of prostaglandin E1 (PGE1) in case 1 and by resection of the necrotic intestine and continuous intra-arterial and/or intravenous injection of PGE1 in case 2. AMO and NOMI have many background similarities (e.g., atherosclerosis, hypertension, and ischemic heart disease), making their coexistence very likely. However, no case of AMO plus NOMI has been reported until now. It is highly probable that concomitant NOMI is overlooked in cases of AMO. When managing AMO, NOMI should be considered as a complication, which may lower the patient's potential risk of developing NOMI and contribute to improved prognosis of both AMO and AMI. PMID- 26806237 TI - Comparison of Nonpenetrating Titanium Clips versus Continuous Polypropylene Suture in Dialysis Access Creation. AB - BACKGROUND: Nonpenetrating titanium surgical clips (clips) offer a theoretical advantage of inducing less intimal hyperplasia at an anastomosis because of less endothelial injury. Whether this translates into improved outcomes when used in the creation of arteriovenous fistulas (AVFs) remains unclear. We sought to compare the maturation, patency, and failure rates of anastomoses created using traditional continuous polypropylene suture and clips. METHODS: All primary AVF created at a single Veterans Administration Medical Center were reviewed over a 6 year period. Anastomoses were created with either clips or suture based on surgeon preference. Patient characteristics and surgical outcomes were collected. Comparisons were made between the 2 groups. RESULTS: Over a 6-year period, 334 fistulas were created (29% suture and 71% clips) in 326 patients. The mean age was 64.8 +/- 11 years with 98% males. Comorbidities included diabetes (70%), hypertension (96.1%), and tobacco use (52.9% previous or current). Approximately half the patients were predialysis. Comparison of patient characteristics showed no differences between the suture and clip groups. There was no significant difference in maturation rate (suture 79% versus clips 72%, P = 0.25), median time to maturation (suture 62 +/- 35 versus clips 71 +/- 13 days, P = 0.07), 1 year primary patency rate (suture 37.4% versus clips 39.6, P = 0.72), 1 year assisted primary patency rate (suture 82.4% versus clips 76.3%, P = 0.31), or overall failure rates (suture 62% versus clips 58%, P = 0.56). Median time to initial failure or reintervention was not significantly different in the clip group (suture 615 [range, 239-991] versus clips 812 [range, 635-989] days, P = 0.72). CONCLUSIONS: Compared to traditional polypropylene suture creation of upper extremity AVFs, nonpenetrating clips had equivalent maturation, 1-year patency, and overall failure rates. Neither clips nor suture offers any clear advantage in the creation of AVF. PMID- 26806238 TI - The Use of AngioVac for Symptomatic Aortic Thrombus Complicated by Mesenteric Ischemia. AB - Aortic thrombus complicated by mesenteric ischemia is a rare but rather challenging entity. With the recent advancements of endovascular techniques, there is a trend to replace the traditional open surgery with an endovascular approach. We report a patient with paravisceral aortic thrombus involving the celiac artery and superior mesenteric artery (SMA). The patient was complaining of worsening abdominal pain, with clinical findings of leukocytosis, normal lactate, and diagnostic laparoscopy demonstrating a segment of threatened jejunum. We describe the novel use of vacuum-assisted suction filtration device in combination with over-the-wire thrombectomy and stenting to successfully restore blood flow within the SMA. The patient had resolution of her symptoms with improved blood flow to the bowel and no need for resection. PMID- 26806239 TI - Concept of Angiosome Does Not Affect Limb Salvage in Infrapopliteal Angioplasty. AB - BACKGROUND: The purpose of this study was to evaluate the importance of the "angiosome" concept in patients with critical limb ischemia treated with infrapopliteal angioplasty, analyzing limb salvage, secondary function, and survival rates between those treated with and without reference to the concept of the angiosome (groups 1 and 2, respectively). METHODS: This was a retrospective, consecutive cohort study that evaluated 95 patients with critical limb ischemia who underwent infrapopliteal angioplasty at the Division of Vascular and Endovascular Surgery, Sao Paulo State Public Servants' Hospital, Brazil, between January 2009 and January 2013. Of the total 92 patients (109 limbs) who underwent angioplasty, 48 (52.2%) patients were in group 1 and 44 (47.8%) patients were in group 2. RESULTS: There was no difference between groups 1 and 2 in terms of the location, lesion severity, or active infection of the infrapopliteal angioplasty. However, groups 1 and 2 differed in their postoperative ankle-brachial indices, which were 0.95 +/- 0.18 and 0.85 +/- 0.18, respectively (P = 0.001). The estimates of limb salvage were similar in groups 1 and 2 (87% and 92.3%, respectively, at 360 days; P = 0.241). The analysis of secondary function did not differ between the 2 groups (65.1% and 58.3%, respectively, within 360 days; P = 0.92). Operative mortality was 8.3% in group 1 and 8% in group 2 (P = 0.60), and survival at 360 days was 78.5% in group 1 and 78.3% in group 2 (P = 0.86), which were not significantly different. CONCLUSIONS: In this study, we found no evidence to support revascularization based on the concept of the angiosome in preference to revascularization of the artery that is most amenable to endovascular treatment for limb salvage and secondary function. PMID- 26806240 TI - Efficacy of the Ulnar-Basilic Arteriovenous Fistula for Hemodialysis: A Systematic Review. AB - BACKGROUND: The fistula first initiative has promoted arteriovenous fistulas (AVFs) as the vascular access of choice. To preserve as many future access options as possible, multiple guidelines advocate that the most distal AVF possible should be created in the first place. Generally, snuff box and radiocephalic (RC) are accepted and well-described sites for AVFs; however, the forearm ulnar-basilic (UB) AVF is seldom used or recommended. The aim of this study is to assess and systematically review the evidence base for the creation of the UB fistula and to critically appraise whether more attention should be given to this site. METHODS: Electronic databases were searched for studies involving the creation of UB fistulas for dialysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcomes for this study were 1-year primary and secondary patency rates. Secondary outcomes were rates of hemodialysis access-induced distal ischemia (HAIDI) and infection. RESULTS: After strict inclusion and/or exclusion criteria by 2 reviewers, 8 studies were included in our review. Weighted-pooled data reveal 1-year primary patency rate for UB AVFs of 53.0% (95% confidence interval [CI]: 40.1-65.8%) with a secondary patency rate of 72.0% (95% CI: 59.2-83.3). HAIDI and infection rates were low. CONCLUSIONS: Our review has shown that the UB AVF may be a viable alternative when a RC AVF is not possible, and dialysis is not required urgently. It has adequate 1-year primary and secondary patency rates and extremely low risk of HAIDI. While it may be more challenging for both surgeons and dialysis nurses to make it a successful vascular access it offers a further option of distal access which may be overlooked. PMID- 26806241 TI - Intravascular Ultrasound-Assisted Crosser System Through the Retrograde Approach to Treat a Trans-Atlantic Inter-Society Consensus D Lesion in the Superficial Femoral Artery After Graft Failure. AB - BACKGROUND: The crosser system is useful to treat chronic total occlusion (CTO) lesions refractory to guidewire recanalization. However, the Inter-Society Consensus for the Management of Peripheral Arterial Disease recommends bypass graft surgery for Trans-Atlantic Inter-Society Consensus (TASC) type D femoropopliteal (FP) lesions. This approach may not be practical in patients with previous graft failure. In these patients, endovascular therapy with the crosser system may be appropriate. However, there are few reports of the crosser system to treat CTO after failure of FP bypass grafts. CASE REPORT: A 74-year-old man with a history of 2 FP bypass grafts presented with left lower-limb ischemic rest pain. Ankle-brachial pressure index (ABPI) in the left leg was 0.45. Angiography revealed a TASC type D lesion in the left superficial femoral artery (SFA). A bidirectional approach was used, but the very stiff dedicated CTO guidewire could not pass through the lesion. Therefore, after confirming that the guidewire was in the true lumen by intravascular ultrasound (IVUS), we used a CROSSER((r)) 14S catheter (Bard Peripheral Vascular Inc., Tempe, AZ) through the retrograde route in the popliteal artery. The lesion was crossed, and a stent was successfully implanted. The patient's symptoms of rest pain resolved with an improved ABPI in the left leg of 0.82 after the procedure. CONCLUSIONS: The crosser system assisted by IVUS through the retrograde approach was useful to treat CTO in the SFA after failure of FP bypass grafts. PMID- 26806242 TI - Clinical Outcomes after Carotid Endarterectomy in Patients with Contralateral Carotid Occlusion. AB - BACKGROUND: Severe carotid stenosis is typically treated with carotid endarterectomy (CEA), but there is debate about the safety of this procedure in patients with contralateral carotid occlusion (CCO). To compare 30-day outcomes after CEA in patients with severe carotid stenosis or without CCO. METHODS: This retrospective, single-institution analysis included 434 patients who underwent CEA. All CEAs were performed under general anesthesia, and carotid shunts were used in 32 patients. Patients were categorized into 2 groups according to patency of the contralateral carotid artery: groups I (no CCO, n = 394) and II (with CCO, n = 40). Demographics, preoperative symptomatic status, and frequency of early (<30 days) symptomatic neurologic complications and death were compared. RESULTS: Total mortality after CEA was 1.6% (n = 7), 7 and 0 in groups I and II, respectively (P = 0.39). Overall stroke rate was 3.5% (n = 15), 15 and 0 in groups I and II, respectively (P = 0.20). Rate of transient ischemic attacks was 1.4% (n = 6), 5 and 1 in groups I and II, respectively (P = 0.37). Symptomatic group I patients had a higher rate of stroke and/or death (6.7% vs. 0%) (P = 0.85). In asymptomatic patients, the stroke and/or death rate was higher in group II (3.4% vs. 8.3%, P < 0.05). In group II, the frequency of shunt placement was higher (3% vs. 53%, P = 0.001). At mean follow-ups of 75.4 +/- 47.5 months (group I) and 72.7 +/- 49.9 months (group II), 157 and 13 additional deaths had occurred in groups I and II, respectively (P = 0.21). CONCLUSIONS: Patients with CCO who undergo CEA do not appear to be at increased risk for perioperative incidence of stroke and/or death, or any neurologic event. PMID- 26806243 TI - Obesity is Not an Independent Factor for Adverse Outcome after Abdominal Aortic Aneurysm Repair. AB - BACKGROUND: The prevalence of obesity is increasing, and its impact on the outcome of open and endovascular abdominal aortic aneurysm (AAA) repair remains unclear, particularly in the European population. We herein assessed the impact of obesity on the postoperative course for both techniques. METHODS: From a database that consecutively collects all patients undergoing AAA repair; we selected all patients undergoing elective surgery for open or endovascular AAA repair, between January 2003 and December 2011. We considered obese patients (body mass index >30 kg/m(2)), overweight (25.1-30 kg/m(2)), and normal-weight patients (18.7-25 kg/m(2)), and compared mortality and/or severe complications at 30 days between obese and nonobese patients (overweight and normal weight) separately for each type of surgery by logistic regression analysis. We analyzed wound complications in the 2 groups. RESULTS: We included 748 patients, 174 obese, and 574 nonobese patients. Obese patients were younger (P < 0.001) and were less likely to have renal failure (P < 0.001) in both techniques. Obese patients in the open repair (OR) group showed a trend toward lower mortality and/or complication rates than in nonobese patients (4.8% vs. 7.5%, P = 0.34). In contrast, in the endovascular aortic aneurysm repair (EVAR) group, obese patients showed a trend toward higher mortality and/or complication rates than nonobese patients (7.1% vs. 3.2%, P = 0.17). In multivariate analysis, obesity was not an independent predictor of outcomes in OR (P = 0.18) or in EVAR (P = 0.20). Wound complications were not higher in obese patients in OR and in EVAR. CONCLUSIONS: Obesity should not be considered an independent risk factor of death and severe complications at 30 days in either open or endovascular AAA repair. Therefore, obesity should not systematically lead to the decision to use EVAR. PMID- 26806244 TI - Old and New Techniques as a Safe Hybrid Approach for Carotid Tandem Lesions. AB - BACKGROUND: Carotid revascularization is performed to prevent stroke. Carotid tandem lesions represent a challenge for treatment, and a hybrid approach may result effective. CASE REPORT: A high-risk 65-year-old woman presented with a "tandem lesion" of left common and internal carotid artery. She was deemed unfit for "simple" standard carotid endarterectomy (CEA). A "single-step" safe hybrid procedure was scheduled for the patient. A "Cormier" carotid vein graft bypass with a retrograde stenting was performed under local anesthesia. CONCLUSIONS: The "safe hybrid procedure" for tandem lesions of the common and internal carotid artery is effective and suitable in high-risk patients in a high-volume centers. PMID- 26806245 TI - Social Media Use among United Kingdom Vascular Surgeons: A Cross-Sectional Study. AB - BACKGROUND: Engagement with social media (SM) is increasing within the general population and medical professionals. Overall, SM engagement is divided between closed, private networks and open, public platforms, such as LinkedIn and Twitter. As engagement with SM is known to vary between specialties, this study was undertaken to evaluate the uptake of SM among vascular surgeons and to describe user demographics associated with SM engagement. METHODS: Vascular surgeons were identified from the 2013 Vascular Society of Great Britain and Ireland Quality Improvement Project and cross-referenced with the General Medical Council registry. Identified individual surgeons were manually searched for on common SM platforms and via Google to identify both SM profiles and personal/partnership practice websites. RESULTS: In total, 472 surgeons (442 men, 93.6%) from 112 National Health Service Trusts were identified. Three hundred forty (63.7%) graduated from UK universities with a mean graduating year of 1987 (range 1969-2000). Cumulatively, they performed 36,300 procedures (mean 72/surgeon; range 3-257). Overall, SM engagement was 47.4%; 217 (46.0%) had LinkedIn accounts and 23 (4.8%) had Twitter profiles. LinkedIn users had a mean of 69 connections (range 0-500+) and had a mean graduating year of 1988 (range 1969-2000). Twitter users had a mean of 258 followers (range 2-2424) and had tweeted a mean of 450 times (range 0-2865); they graduated more recently than their non-Twitter engaged colleagues (mean graduation 1991 vs. 1987, P = 0.006). Overall, SM usage was associated with a more recent graduation (P = 0.038) and with working in the private sector (21.4% vs. 13.7%, P = 0.029). There were demographic differences between those who had LinkedIn and Twitter accounts. CONCLUSIONS: Twitter and LinkedIn engagement among vascular surgeons is higher than that of other surgical specialties. There is a significant link between the experience of the surgeon and with SM use. PMID- 26806246 TI - Do Medications Commonly Prescribed to Patients with Peripheral Arterial Disease Have an Effect on Nutritional Status? A Review of the Literature. AB - BACKGROUND: Polypharmacy is common among patients with peripheral arterial disease (PAD) with a combination of medications used for risk-factor modification and medical management of the disease itself. Interaction between commonly prescribed medications and nutritional status has not previously been well described. This review aims to critically appraise evidence exploring associations between medications commonly prescribed to patients with PAD and nutritional status and provide recommendations for practice. METHODS: A comprehensive literature search was conducted to locate studies relating to nutrient interactions among lipid-lowering, antihypertensive, antiplatelet, and oral hypoglycemic drug classes. Quality of the evidence was rated on the basis of recommendations by the National Health and Medical Research Council. RESULTS: A total of 25 articles were identified as suitable and included in the review. No studies were specific to patients with PAD, and hence findings highlighting risk of ubiquinone (coenzyme Q10 [CoQ10]) depletion with lipid-lowering medications, zinc depletion with antihypertensive medications, and vitamin B12 depletion with oral hypoglycemic medications are extrapolated from heterogeneous groups of patients and healthy adults. The body of evidence ranged in quality from satisfactory to poor. CONCLUSIONS: High-quality research is required to confirm the interactions suggested by the included studies in patients with PAD specifically. It is, however, recommended that patients with PAD that are long term consumers of the selected medications are monitored for CoQ10, zinc, and vitamin B12 to facilitate early identification of deficiencies and initiation of treatment. Treatment may involve dietary intervention and/or supplementation. PMID- 26806247 TI - Simultaneous Open Surgical Treatment of Aortic Coral Reef and Leriche Syndrome: Case Report and Literature Review. AB - The coral reef aorta (CRA) is a rare syndrome commonly referred to a distribution of calcified plaques in the visceral part of the aorta. Because those plaques can cause malperfusion of the lower limbs, visceral ischemia or renovascular hypertension, surgical treatment is recommended. Transaortic endarterectomy is accepted as a standard repair and it is often performed through an extensive thoracoabdominal approach. CRA has been reported in association with polidistrectual atherosclerotic disease, such as Leriche syndrome. When these 2 conditions coexist, surgical invasivity increases raising several issues concerning the type of surgical access and the revascularization techniques. We report the case of a patient with CRA and Leriche syndrome treated by simultaneous aortic endarterectomy and aortibifemoral bypass at our institution. Intervention was performed through left lumbotomy at 10th intercostal space extended by a left pararectal abdominal incision with section of 11th rib. Through extraperitoneal access visceral vessels were isolated. Aortic cross clamping was performed at supraceliac and infrarenal levels and a longitudinal arteriotomy was performed on the posterolateral wall of visceral aorta for an overall 4-cm extension. Aortic endarterectomy was then performed and complete plaque excision was easily achieved. Superior mesenteric artery angioplasty was then performed by a DeBakey dilator, gaining an optimal backflow. The aortotomy was then closed with running 3-0 polypropylene suture. Subsequently, through a transperitoneal access an aortobi-femoral bypass was performed by a Dacron knitted graft. Postoperative course was uneventful. At a 6-month follow-up, the patient is in good clinical condition with normal patency of visceral vessels. PMID- 26806248 TI - Learning Curve of Robotic-Assisted Anastomosis: Shorter than the Laparoscopic Technique? An Educational Study. AB - BACKGROUND: Achieving aortic anastomosis in laparoscopic surgery remains a technical challenge. The Da Vinci robot could theoretically counteract this issue by minimizing the technical challenge. The aim of this study was to compare the learning curves of performing vascular anastomoses by trainees without any experience using purely laparoscopic versus robotic-assisted techniques. METHODS: Surgery residents were randomly included in the laparoscopic group (group A, n = 3) and the robotic group (group B, n = 3). They performed 10 end-to-end anastomoses on 18-mm-diameter tubular expanded polytetrafluoroethylene grafts. The parameters recorded were duration to complete the anastomosis and an indirect sealing quality evaluation (ISQE) defined as the following ratio: number of stitches with a distance of less than 4 mm/total number of stitches. RESULTS: The mean duration to perform the anastomosis decreased from 2340 s (+/-64) for the first anastomosis to 651 s (+/-248) for the last in group A (P < 0.05) and from 1989 s (+/-556) to 801 s (+/-120) in group B (P < 0.05). The mean ISQE increased from 74% (+/-18) for the first anastomosis to 98% (+/-3) for the last in group A (P < 0.05) and decreased from 100% to 98% (+/-2) in group B (nonsignificant). The mean duration to perform the first anastomosis was lower in group B than in group A (P < 0.05). The mean duration to perform the last anastomosis was not significantly different between the groups. Sealing tended to be better in group B for the first anastomosis compared with group A. CONCLUSIONS: Minimally invasive laparoscopic technique training demonstrates a learning curve to perform vascular anastomoses. The robotic-assisted technique tended to improve suturing skills and should be considered as a valuable tool to reduce the technical learning curve. PMID- 26806249 TI - Fenestrated and Branched Endograft after Previous Aortic Repair. AB - BACKGROUND: Para-anastomotic aneurysms (P-AAA) and proximal aortic aneurysmal degeneration after previous aortic open repair (OR) or endovascular repair (EVAR) are challenging clinical scenarios. OR is technically demanding, and standard EVAR could be impossible due to the absence of proximal landing zone. The aim of the study is to report midterm results of fenestrated and branched endografts (FB EVAR) to treat proximal aortic lesions after previous aortic repair. METHODS: Since 2010, patients that underwent FB-EVAR after previous aortic repair were prospectively enrolled. Clinical or morphologic or intraoperative or postoperative data were collected and retrospectively analyzed. Primary end points were technical success and clinical success. Secondary end points were procedure-related events (endoleaks, target visceral vessels occlusion, mortality), midterm survival and freedom from FB-EVAR-related reinterventions. RESULTS: Twenty patients (Male: 98%, age: 75 +/- 6 years, American Society of Anesthesiologists [ASA] >= III: 100%) were enrolled. Fifteen patients (75%) underwent previous aortic OR and 5 (25%) standard EVAR. The mean time since the previous treatment was 12 +/- 10 years. Present aortic lesions included thoracoabdominal aneurysms 12 (60%) and juxtarenal and pararenal aneurysms 8 (40%). The mean aortic aneurysm diameter was 67 +/- 15 mm. All patients were at high risk for OR and had anatomies precluding standard EVAR. Seventy-two visceral vessels (renal arteries: 34, superior mesenteric artery: 20, celiac trunk: 18) were targeted: 49 fenestrations, 19 branches, and 4 scallops. An FB-EVAR tube and trimodular endograft was planned in 17 and 3 cases, respectively. Technical success was 95%; operative target vessel perfusion was 98.5%. Thirty-day mortality was 0%. Clinical success was 80% because there was a transient renal function worsening in 4 patients (>30% of baseline). One distal type I endoleak was detected and treated at 1-month. The mean follow-up was 15 +/- 11 months. There were not proximal type I endoleaks, target visceral vessel occlusions, or aneurismal-related mortality. Survival at 1 year was 85 +/- 5%. One late FEVAR related reintervention occurred. CONCLUSIONS: According to the reported data, FB EVAR for treating P-AAA or proximal aneurysmal degeneration after previous aortic OR/EVAR in high-risk patients is a safe and/or effective solution. PMID- 26806250 TI - Mechanism and Management of Retrograde Type A Aortic Dissection Complicating TEVAR for Type B Aortic Dissection. AB - BACKGROUND: This study is to investigate the causes, treatment methods, and preventive measures of retrograde type A aortic dissection (RAAD) complicating thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). METHODS: From January 2005 to December 2013, 360 TBAD patients receiving TEVAR were enrolled in this study. Among them, 304 cases were male and 56 cases were female. They were from 19 to 85 years old, with a mean age of 52 +/- 12.8 years old. The average follow-up time was 32 +/- 11.3 months (3-63 months), the follow up rate was 69.1% (249 cases), and the lost rate was 30.9% (111 cases). The reasons and the treatment methods of RAAD complicating TEVAR for TBAD were analyzed. RESULTS: There were 5 cases of RAAD complicating TEVAR in TBAD (1.4%) patients, among them, 4 cases were male and 1 case was female. TEVAR operation failed in 1 case because of RAAD occurrence during TEVAR. This case was treated with open operation. In the other 4 cases, TEVAR operation was successfully carried out. During follow-up, RAAD was found in 3 cases within 1 month after TEVAR and in 1 case at 1 year after TEVAR. Conservative treatment was applied to 2 cases, whereas surgical operation treatment was performed in the other 3 cases. One case of conservative treatment patient was dead, and the other 4 cases are still alive. CONCLUSIONS: Incomplete design of stent-graft system, rough handling and presence of vascular wall lesions are the main reasons of RAAD complicating TEVAR for TBAD. Surgical operation is the most effective treatment measure for RAAD complicating TEVAR for TBAD. PMID- 26806251 TI - Thoracic Endovascular Aortic Repair Combined with Assistant Techniques and Devices for the Treatment of Acute Complicated Stanford Type B Aortic Dissections Involving Aortic Arch. AB - BACKGROUND: The present study retrospectively reviewed and evaluated the effectiveness of thoracic endovascular aortic repair (TEVAR) combined with assistant techniques and devices for the treatment of acute complicated Stanford type B aortic dissections involving aortic arch. METHODS: Fifty-six patients with acute complicated Stanford type B aortic dissection involving aortic arch were treated with TEVAR combined with hybrid procedure, chimney-graft technique, and branched stent grafts from January 2009 to March 2014. RESULTS: Seventeen patients undergone TEVAR combined with hybrid technique. Technical success was achieved in 94.1% with 5.8% of early mortality. Strokes occurred in a patient developing paraplegia, who completely recovered after lumbar drainage. Cardiocirculatory and pulmonary complications, bypass dysfunction or severe endoleak was not observed. Thirty patients undergone TEVAR combined with chimney technique with 100% technical success rate. Chimney-stent compression was observed in 1 patient, and another bare stent was deployed inside the first one. Three patients (10%) died during the study period. Immediate postoperative type I endoleak was detected in 4 cases (13.3%). TEVAR assisted by Castor branched aortic stent grafts in 9 patients was successful. Mortality during perioperative period and 30 days after TEVAR was null. No serious complications such as strokes, acute myocardial infarction, and ischemia of arms occurred. CONCLUSIONS: The results indicate that TEVAR combined with hybrid technique, chimney technique, and branched stent grafts is proven to be a technically feasible and effective treatment for acute complicated Stanford type B aortic dissection involving aortic arch in small cohort. PMID- 26806252 TI - Osteochondromas: An Unusual Cause of Vascular Disease in Young Patients: 2 Clinical Cases. AB - Osteochondroma is the most common benign tumor of bones in young patients. It is an unusual cause of nonatherosclerotic peripheral arteriopathy. It is mostly detected in youth and, thus, diagnosis can be delayed since symptoms such as claudication can be confused with muscular cramps. In case of clinical suspicion of peripheral artery disease in the young, the presence of an exostosis should be suspected. We reported our experience of 2 young patients with limb ischemia due to ab extrinseco compression of popliteal artery. In both cases, surgical exeresis of a lower limb exostosis was performed. In the first case, bypass surgery was not required since arterial wall was not damaged. In the second case, an autologous inverted saphenous vein femoro popliteal bypass was performed. PMID- 26806253 TI - LA-ICP-MS imaging in multicellular tumor spheroids - a novel tool in the preclinical development of metal-based anticancer drugs. AB - A novel application of advanced elemental imaging offers cutting edge in vitro assays with more predictive power on the efficacy of anticancer drugs in preclinical development compared to two dimensional cell culture models. We propose LA-ICP-MS analysis of multicellular spheroids, which are increasingly being used as three dimensional (3D) models of tumors, for improving the in vitro evaluation of anticancer metallodrugs. The presented strategy is very well suited for screening drug-tumor penetration, a key issue for drug efficacy. A major advantage of tumor spheroid models is that they enable us to create a tissue-like structure and function. With respect to 2D culture on the one hand and in vivo models on the other, multicellular spheroids thus show intermediate complexity, still allowing high repeatability and adequate through-put for drug research. This strongly argues for the use of spheroids as bridging models in preclinical anticancer drug development. Probing the lateral platinum distribution within these tumor models allows visualizing the penetration depth and targeting of platinum-based complexes. In the present study, we show for the first time that spatially-resolved metal accumulation in tumor spheroids upon treatment with platinum compounds can be appropriately assessed. The optimized LA-ICP-MS setup allowed discerning the platinum localization in different regions of the tumor spheroids upon compound treatment at biologically relevant (low micromolar) concentrations. Predominant platinum accumulation was observed at the periphery as well as in the center of the spheroids. This corresponds to the proliferating outermost layers of cells and the necrotic core, respectively, indicating enhanced platinum sequestration in these regions. PMID- 26806254 TI - Emergency and elective pulmonary surgical resection in haematological patients with invasive fungal infections: a report of 50 cases in a single centre. AB - Invasive fungal infections (IFI) remain life-threatening complications in haematological patients. The aim of the study was to present the experience of a single centre in the surgical treatment of pulmonary IFI. Between 1992 and 2014, 50 haematological patients with IFI underwent pulmonary resection. In 27 cases it was an emergency procedure to avoid haemoptysis (if the lesion threatened pulmonary vessels). The remaining 23 patients underwent elective surgery before new chemotherapy or stem-cell transplantation. Among these patients (median age: 54 years; range: 5-70 years), 92% had acute leukaemia and 68% were on haematological first-line therapy (receiving induction or consolidation chemotherapies). Invasive pulmonary aspergillosis and pulmonary mucormycosis were diagnosed in 37 and 12 patients, respectively. One patient had IFI due to Trichoderma longibrachiatum. All of the patients received antifungal agents. In the month preceding IFI diagnosis, 94% of patients had been neutropenic. At the time of surgery, 30% of patients were still neutropenic and 54% required platelet transfusions. Lobectomy or segmentectomy were performed in 80% and 20% of cases, respectively. Mortality at 30 and 90 days post-surgery was 6% and 10%, respectively. After surgery, median overall survival was 21 months; median overall survival was similar between patients with emergency or elective surgery and between the types of IFI (invasive pulmonary aspergillosis or pulmonary mucormycosis). However, overall survival was far better in haematological first line patients or in those achieving a haematological complete response than in other patients (p <0.001). In pulmonary IFI, lung resection could be an effective complement to medical treatment in selected haematological patients. PMID- 26806256 TI - Hospitalization in double-occupancy rooms and the risk of hospital-acquired influenza: a prospective cohort study. AB - Hospitalization in double-occupancy rooms and the risk of hospital-acquired influenza were assessed prospectively. The incidence was 2.0 for 100 patient-days in double- vs. 0.7 in single-occupancy rooms (p 0.028). The adjusted hazard ratio of hospital-acquired influenza was 2.67 (95% confidence interval 1.05-6.76) in patients hospitalized in double- compared to single-occupancy rooms. PMID- 26806255 TI - Celecoxib does not alter intestinal microbiome in a longitudinal diet-controlled study. PMID- 26806257 TI - Maraviroc contributes to the restoration of the homeostasis of regulatory T-cell subsets in antiretroviral-naive HIV-infected subjects. AB - Regulatory T (Treg) cells comprise different functional subsets with different CCR5 expression. Treg homeostasis is disrupted by HIV but the effect of treatment has barely been explored. In a longitudinal design, we compared the effect of a maraviroc-containing (n = 9) or sparing (n = 12) therapy in antiretroviral-naive HIV-positive participants on peripheral FoxP3(low) CD45RA(+) (nTreg), FoxP3(high) CD45RA(-) (eTreg) and FoxP3(low) CD45RA(-) (non-Treg) cells. Maraviroc significantly reduced all subsets in the short-term and, except for nTreg cells, also normalized them in the long-term. The correlation between eTreg cells and CD4 counts, lost before treatment, was only restored by maraviroc. The differential effect of maraviroc on Treg subsets contributes to understanding its immunomodulatory effects. PMID- 26806259 TI - Why is antibiotic resistance a deadly emerging disease? AB - Evolution of bacteria towards resistance to antimicrobial agents, including multidrug resistance, is unavoidable because it represents a particular aspect of the general evolution of bacteria that is unstoppable. Therefore, the only means of dealing with this situation is to delay the emergence and subsequent dissemination of resistant bacteria or resistance genes. In this review, we will consider the biochemical mechanisms and the genetics that bacteria use to offset antibiotic selective pressure. The data provided are mainly, if not exclusively, taken from the work carried out in the laboratory, although there are numerous other examples in the literature. PMID- 26806258 TI - Comparison of community-onset Staphylococcus argenteus and Staphylococcus aureus sepsis in Thailand: a prospective multicentre observational study. AB - Staphylococcus argenteus is a globally distributed cause of human infection, but diagnostic laboratories misidentify this as Staphylococcus aureus. We determined whether there is clinical utility in distinguishing between the two. A prospective cohort study of community-onset invasive staphylococcal sepsis was conducted in adults at four hospitals in northeast Thailand between 2010 and 2013. Of 311 patients analysed, 58 (19%) were infected with S. argenteus and 253 (81%) with S. aureus. Most S. argenteus (54/58) were multilocus sequence type 2250. Infection with S. argenteus was more common in males, but rates of bacteraemia and drainage procedures were similar in the two groups. S. argenteus precipitated significantly less respiratory failure than S. aureus (5.2% versus 20.2%, adjusted OR 0.21, 95% CI 0.06-0.74, p 0.015), with a similar but non significant trend for shock (6.9% versus 12.3%, adjusted OR 0.46, 95% CI 0.15 1.44, p 0.18). This did not translate into a difference in death at 28 days (6.9% versus 8.7%, adjusted OR 0.80, 95% CI 0.24-2.65, p 0.72). S. argenteus was more susceptible to antimicrobial drugs compared with S. aureus, and contained fewer toxin genes although pvl was detected in 16% (9/58). We conclude that clinical differences exist in association with sepsis due to S. argenteus versus S. aureus. PMID- 26806260 TI - Prospective assessment of rapid diagnostic tests for the detection of antibodies to hepatitis C virus, a tool for improving access to care. AB - Large-scale hepatitis C screening is required to prevent further spread of the infection, improve access to care in the context of new hepatitis C virus (HCV) drug regimens without interferon-alpha and subsequently reduce the risk of long term complications of chronic liver disease. Rapid diagnostic tests (RDTs) represent an attractive alternative to enzyme immunoassay using blood from venepuncture. The aim of the present study was to prospectively assess the clinical performance of CE-marked RDTs detecting anti-HCV antibodies in fingerstick capillary whole blood and/or oral fluid. A total of 513 individuals, including 318 patients with chronic HCV infection, 25 patients with resolved HCV infection and 170 HCV-seronegative individuals, were prospectively enrolled. The specificity of RDTs with fingerstick whole blood varied from 98.8% to 100%. The clinical sensitivity was high for the OraQuick((r)) and Toyo((r)) tests (99.4% and 95.8%, respectively), but low for the Labmen((r)) test (63.1%). The specificity and clinical sensitivity in crevicular fluid were both satisfactory for the OraQuick((r)) test (100% and 97.6%, respectively). HCV antibody RDTs were easy and rapid to perform in the context of patient care. They were highly specific. Both the OraQuick((r)) and Toyo((r)) tests reached the expected level of performance for wide-scale use, with a performance advantage for the OraQuick((r)) HCV test. RDTs appear to be a promising new tool for wide-scale screening of HCV infection in high-risk to medium-risk populations. Hence, careful assessment of the performance of HCV RDTs must be recommended before they can be implemented in clinical practice. PMID- 26806262 TI - Erratum. PMID- 26806261 TI - Update on Canine and Feline Blood Donor Screening for Blood-Borne Pathogens. AB - An update on the 2005 American College of Veterinary Internal Medicine (ACVIM) Consensus Statement on blood donor infectious disease screening was presented at the 2015 ACVIM Forum in Indianapolis, Indiana, followed by panel and audience discussion. The updated consensus statement is presented below. The consensus statement aims to provide guidance on appropriate blood-borne pathogen testing for canine and feline blood donors in North America. PMID- 26806265 TI - Early lesion-specific (18)F-FDG PET response to chemotherapy predicts time to lesion progression in locally advanced non-small cell lung cancer. AB - BACKGROUND AND PURPOSE: We hypothesize that the lesion-to-lesion variability in FDG-PET response after one cycle of chemotherapy for NSCLC in an individual patient may inform radiation dose redistribution. To test this hypothesis, we investigate if time to lesion-progression in patients with multiple lesions is dependent on lesion-specific response to chemotherapy. MATERIALS AND METHODS: We analyzed 81 patients with 184 lesions referred to curative chemo-radiotherapy for NSCLC 2010-2012. (18)F-FDG PET scans were performed at diagnosis and after one series of chemotherapy. Response of each lesion was assessed as the change in FDG peak standardized uptake value. Variance of lesion response was compared within and between patients. Time to progression for each lesion was analyzed using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: Within patient variability in lesion responses was of the same magnitude as the between patient variability. Lesion-specific time to progression was longer in lesions with a better response (log-rank p=0.038). Nodal lesions had a much lower risk of progression than T-site lesions (HR=0.09, p<0.0001). CONCLUSIONS: Recording an overall patient response involves a loss of biological information on heterogeneity between lesions. Poor lesion-specific response after one cycle chemotherapy may identify lesions that would benefit from an individualized radiotherapy strategy. PMID- 26806264 TI - Risk factors for vertebral compression fractures in preoperative chemoradiotherapy with gemcitabine for pancreatic cancer. AB - BACKGROUND AND PURPOSE: Preoperative chemoradiotherapy (CRT) with gemcitabine (GEM) for pancreatic cancer is often accompanied by vertebral compression fractures (VCFs). This study aimed to establish the incidence of VCFs and identify the related risk factors (RFs) to elucidate how to decrease the overall incidence of VCF. MATERIAL AND METHODS: We investigated 220 patients with resectable or borderline-resectable pancreatic cancers who had completed preoperative CRT between 2006 and 2011. The RFs associated with VCF were analyzed in a total of 1308 thoracolumbar vertebral bodies. RESULTS: Thirty-seven VCFs occurred in 25 patients (11%); the cumulative incidence at two years was 18.9%. Univariate analysis revealed female sex, age and high daily GEM concentration during radiotherapy as RFs for VCF. The multivariate mixed effects logistic regression model demonstrated that the most responsible factor was radiation dose (p<0.001). We estimated the radiation condition resulting in a fracture incidence of ?5% by counting the patient's number of the three RFs. For patients with three factors, the mean vertebral dose was 22.0 Gy. CONCLUSIONS: The RFs for VCF after CRT were identified. The side effect of VCF might be avoided by regulating the radiation dose to neighboring vertebral bodies after considering the RFs. PMID- 26806268 TI - A convenient domino Ferrier rearrangement-intramolecular cyclization for the synthesis of novel benzopyran-fused pyranoquinolines. AB - The Ferrier rearrangement and the Povarov reaction have proven indispensable tools in carbohydrate chemistry and the synthesis of N-heterocycles, respectively. We hereby report a one-pot cyclization sequence involving the Ferrier and Povarov-like reactions in the synthesis of novel pentacyclic N heterocycles: benzopyran-fused pyranoquinolines. The reaction entails three component condensation of a glycal with a variety of anilines and 2 hydroxybenzaldehydes under Lewis acid catalysis to yield the title compounds in 4 24 hours of reaction time, in moderate to high yields and excellent diastereoselectivity. Of the Lewis acid catalysts deployed [Sc(OTf)3, Al(OTf)3, Cu(OTf)2, CuOTf, I2, InCl3, and La(OTf)3] in various solvents (acetonitrile, THF, dichloromethane, 1,2-dichloroethane and diethyl ether) at room and elevated temperatures, Sc(OTf)3 (10 mol%) in acetonitrile at 70 degrees C gave the best results, with excellent diastereoselectivity. CAN-mediated oxidative ring opening of the pentacyclic N-heterocycle gave the corresponding enantiometrically pure chromenoquinoline bearing a pendant sugar moiety. PMID- 26806266 TI - Radiation sparing of cerebral cortex in brain tumor patients using quantitative neuroimaging. AB - BACKGROUND AND PURPOSE: Neurocognitive decline in brain tumor patients treated with radiotherapy (RT) may be linked to cortical atrophy. We developed models to determine radiation treatment-planning objectives for cortex, which were tested on a sample population to identify the dosimetric cost of cortical sparing. MATERIAL AND METHODS: The relationship between the probability of cortical atrophy in fifteen high-grade glioma patients at 1-year post-RT and radiation dose was fit using logistic mixed effects modeling. Cortical sparing was implemented using two strategies: region-specific sparing using model parameters, and non-specific sparing of all normal brain tissue. RESULTS: A dose threshold of 28.6 Gy was found to result in a 20% probability of severe atrophy. Average cortical sparing at 30 Gy was greater for region-specific dose avoidance (4.6%) compared to non-specific (3.6%). Cortical sparing resulted in an increase in heterogeneity index of the planning target volume (PTV) with an average increase of 1.9% (region-specific) and 0.9% (non-specific). CONCLUSIONS: We found RT doses above 28.6 Gy resulted in a greater than 20% probability of cortical atrophy. Cortical sparing can be achieved using region-specific or non-specific dose avoidance strategies at the cost of an increase in the dose heterogeneity of the PTV. PMID- 26806271 TI - Process improvement in surgery. PMID- 26806274 TI - Synthesis of MOF templated Cu/CuO@TiO2 nanocomposites for synergistic hydrogen production. AB - A copper metal-organic framework (Cu-MOF) provides access to Cu/CuO@TiO2 hybrid nanocomposites with highly dispersive copper species adsorbed on a TiO2 semiconducting system. This novel nanostructure exhibits efficient hydrogen evolution performance under solar illumination of intensity ~1 Sun. The rate of H2 production was systematically optimized under different operational parameters. Experimental observation reveals that mesoporous Cu/CuO@TiO2 nanocomposite with 0.5 wt% Cu loading showed the highest rate of H2 production (286 mmol g(-1) h(-1)), which is considerably higher than that of CuO loaded TiO2 prepared using a conventional impregnation method. This high photocatalytic H2 production activity is attributed predominantly to the presence of surface deposited Cu(0) species and the small size of the heterojunction (1-2 nm) between CuO and TiO2, which facilitate interfacial charge carrier transfer from the TiO2 nanoparticles. The catalyst showed good recyclability under prolonged exposure (30 h) to solar irradiation. Unlike many Pt decorated TiO2 photocatalysts, this hybrid photocatalyst provides an inexpensive means of harnessing solar energy. PMID- 26806273 TI - Worries About Labor and Birth: A Population-Based Study of Outcomes for Young Primiparous Women. AB - BACKGROUND: Pregnancy at a young age is a continuing public health concern strongly associated with socioeconomic deprivation, social isolation, and stigma. The objectives were to see whether, compared with women aged 21 or more, women aged 20 years or younger worried more about labor and birth, and had poorer maternal outcomes. Another objective was to investigate the extent to which worries about labor and birth mediated the associations between young age and outcomes. METHODS: A secondary analysis of data was conducted relating to 2,598 primiparous women's experience of maternity care in England in 2010. The survey collected data on care in the antenatal, intrapartum, and postnatal periods, and sociodemographic factors. A validated checklist measured worries about labor and birth. RESULTS: Compared with women aged 21 or more, women aged 20 years or younger worried more about labor and birth. The pain and duration of labor worried all women and those aged 20 years or younger were particularly worried about the uncertainty of labor onset, cesarean section birth, and about embarrassment. In logistic regression, after adjusting for potential confounders, young age was a significant independent risk factor for worries about pain and distress in labor, and self-reported depression at 1 and 3 months. However, young age was also significantly associated with having a normal vaginal delivery. CONCLUSIONS: It may be appropriate to focus support on women experiencing multiple disadvantage, rather than young age alone. PMID- 26806272 TI - Preliminary treatment results of proton beam therapy with chemoradiotherapy for stage I-III esophageal cancer. AB - The effect of proton beam therapy (PBT) on various cancers is controversial. We aimed to evaluate the efficacy and safety of PBT with alternating chemoradiotherapy (ACRT) for patients with stage I-III esophageal cancer. Two cycles of systemic chemotherapy with a continuous infusion of 5-fluorouracil (5 FU) on days 1-5 and a 5h infusion of nedaplatin (NDP) on day 6 were accompanied by thoracic irradiation using X-ray therapy and PBT. During the first half of the treatment, X-rays were delivered to the prophylactic area. During the second half of the treatment, proton beams were used to irradiate the involved field. To reduce the dose of cardiac irradiation, proton beams were delivered with posterior and posterior oblique angles. Between January 2009 and December 2012, 47 patients were enrolled in this study. The median follow-up duration was 29 months for all patients and 40 months for survivors. The 3 year overall survival rate, progression-free survival rate, and local control rate were 59.2%, 56.3%, and 69.8%, respectively. With respect to grade 3-4 late toxicities, there were no pleural or pericardial effusions, but two patients (4.3%) had esophageal stenosis, one patient (2.1%) had fistula, and two patients (4.3%) developed radiation pneumonitis. PBT with ACRT might have the potential to reduce the risk of cardiac damage and might become one of the primary methods of esophageal cancer treatment. PMID- 26806276 TI - Isolated ileitis associated with primary sclerosing cholangitis in three patients with Crohn's disease. AB - BACKGROUND: Primary sclerosing cholangitis (PSC) is associated with ulcerative colitis and extensive colonic involvement or ileocolitis in Crohn's disease (CD). To our knowledge, no specific report of isolated ileitis associated with PSC in CD patients has been published in CD patients. AIM AND METHODS: We report three cases of patients with isolated Crohn's ileitis associated with PSC and in whom colonic inflammation was never documented. RESULTS: Patients were followed up 10 23 years and each patient underwent 6-7 ileocolonoscopies: inflammation was located only in the terminal ileum, which was confirmed on surgical specimens in two patients. Small-duct PSC led to diagnosis of CD ileitis in one patient, while small and large-ducts PSC were evidenced after CD diagnosis in the other 2. PSC were regularly followed for 9-10 years. CONCLUSIONS: Our three cases of PSC with isolated CD ileitis and long-term follow-up without any sign of colonic involvement argue against the concept that colonic mucosal inflammation is critical for the pathogenesis of PSC in inflammatory bowel disease. PMID- 26806279 TI - Twelve tips for medical curriculum design from a cognitive load theory perspective. AB - During their course, medical students have to become proficient in a variety of competencies. For each of these competencies, educational design can use cognitive load theory to consider three dimensions: task fidelity: from literature (lowest) through simulated patients (medium) to real patients (highest); task complexity: the number of information elements in a learning task; and instructional support: from worked examples (highest) through completion tasks (medium) to autonomous task performance (lowest). One should integrate any competency into a medical curriculum such that training in that competency facilitates the students' journey that starts from high instructional support on low-complexity low-fidelity learning tasks all the way to high complexity tasks in high-fidelity environments carried out autonomously. This article presents twelve tips on using cognitive load theory or, more specifically, a set of four tips for each of task fidelity, task complexity, and instructional support, to achieve that aim. PMID- 26806277 TI - Glycine blocks long-term potentiation of GABAergic synapses in the ventral tegmental area. AB - The mesocorticolimbic dopamine system, originating in the ventral tegmental area (VTA) is normally constrained by GABA-mediated synaptic inhibition. Accumulating evidence indicates that long-term potentiation of GABAergic synapses (LTPGABA) in VTA dopamine neurons plays an important role in the actions of drugs of abuse, including ethanol. We previously showed that a single infusion of glycine into the VTA of rats strongly reduces ethanol intake for 24h. In the current study, we examined the effect of glycine on the electrophysiological activities of putative dopamine VTA neurons in midbrain slices from ethanol-naive rats. We report here that a 15-min exposure to 10 MUM glycine prevented trains of high-frequency stimulation (HFS) from producing LTPGABA, which was rescued by the glycine receptor (GlyR) antagonist strychnine. Glycine also concentration-dependently decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs). By contrast, glycine pretreatment did not prevent potentiation of inhibitory postsynaptic currents (IPSCs) during a continuous exposure to the nitric oxide (NO) donor, SNAP (S-nitroso-N-acetylpenicillamine), or a brief exposure to 10 MUM glycine and 10 MUM NMDA (N-methyl-D-aspartate), an agonist of NMDA-type glutamate receptors. Thus, the blockade of LTPGABA by glycine is probably resulted from suppressing glutamate release by activating the GlyRs on the glutamatergic terminals. This effect of glycine may contribute to the reduction in ethanol intake induced by intra-VTA glycine observed in vivo. PMID- 26806282 TI - Clinical and Pathological Aspects of Melanoma among Children in Finland. PMID- 26806281 TI - Genetic basis of TNF-alpha antagonist associated psoriasis in inflammatory bowel diseases: a genotype-phenotype analysis. AB - BACKGROUND: Anti-tumour necrosis factor (anti-TNF) biologic associated psoriasis has been reported in inflammatory bowel disease (IBD) patients. However, little is known regarding its pathogenesis. AIM: To identify potential genetic predispositions to anti-TNF associated psoriasis in IBD patients. METHODS: This retrospective chart review included IBD patients enrolled in a prospective registry. Cases of anti-TNF associated psoriasis and idiopathic psoriasis unrelated to anti-TNF exposure were confirmed by an expert dermatologist. All patients were genotyped on the Illumina Immunochip. A weighted genetic risk score ascertaining genetic pre-disposition towards psoriasis was calculated and overall genetic pre-disposition as well as differential distribution of individual polymorphisms was compared across the three groups. RESULTS: Our study included 724 IBD patients who initiated anti-TNF therapy and did not develop psoriasis, 35 patients with anti-TNF associated psoriasis, and 38 patients with idiopathic psoriasis. Anti-TNF users who developed psoriasis had a modest but statistically significantly greater psoriasis genetic risk score than anti-TNF controls (mean 0.64 vs. 0.61, P = 0.04), and had a similar genetic risk score as those with idiopathic psoriasis (0.64 vs. 0.62, P = 0.22). Two loci associated with NOS2 and ETS1 genes achieved P < 0.05 when comparing anti-TNF associated psoriasis to anti TNF controls. Three loci were significantly different between anti-TNF associated psoriasis and idiopathic psoriasis including a polymorphism near NOS2 encoding for inducible nitric oxide synthase that is produced by dendritic cells in skin lesions in psoriasis. CONCLUSION: Patients with anti-TNF associated psoriasis had a modestly greater genetic pre-disposition towards psoriasis but no single causative polymorphism was identified. PMID- 26806283 TI - Electrochemical hydrogen sulfide biosensors. AB - The measurement of sulfide, especially hydrogen sulfide, has held the attention of the analytical community due to its unique physiological and pathophysiological roles in biological systems. Electrochemical detection offers a rapid, highly sensitive, affordable, simple, and real-time technique to measure hydrogen sulfide concentration, which has been a well-documented and reliable method. This review details up-to-date research on the electrochemical detection of hydrogen sulfide (ion selective electrodes, polarographic hydrogen sulfide sensors, etc.) in biological samples for potential therapeutic use. PMID- 26806284 TI - Evidence of multimicrometric coherent gamma' precipitates in a hot-forged gamma gamma' nickel-based superalloy. AB - This paper demonstrates the existence of large gamma' precipitates (several micrometres in diameter) that are coherent with their surrounding matrix grain in a commercial gamma-gamma' nickel-based superalloy. The use of combined energy dispersive X-ray spectrometry and electron backscattered diffraction (EBSD) analyses allowed for revealing that surprising feature, which was then confirmed by transmission electron microscopy (TEM). Coherency for such large second-phase particles is supported by a very low crystal lattice misfit between the two phases, which was confirmed thanks to X-ray diffractograms and TEM selected area electron diffraction patterns. Dynamic recrystallization of polycrystalline gamma gamma' nickel-based superalloys has been extensively studied in terms of mechanisms and kinetics. As in many materials with low stacking fault energy, under forging conditions, the main softening mechanism is discontinuous dynamic recrystallization. This mechanism occurs with preferential nucleation on the grain boundaries of the deformed matrix. The latter is then being consumed by the growth of the newly formed grains of low energy and by nucleation that keeps generating new grains. In the case of sub-solvus forging, large gamma' particles usually pin the migrating boundaries and thus limit grain growth to a size which is determined by the distribution of second-phase particles, in good agreement with the Smith-Zener model. Under particular circumstances, the driving force associated with the difference in stored energy between the growing grains and the matrix can be large enough that the pinning forces can be overcome, and some grains can then reach much larger grain sizes. In the latter exceptional case, some intragranular primary gamma' particles can be observed, although they are almost exclusively located on grain boundaries and triple junctions otherwise. In both cases, primary precipitates have no special orientation relationship with the surrounding matrix grain(s). This paper demonstrates the existence of high fractions of large gamma' precipitate (several micrometres in diameter) that are coherent with their surrounding matrix grain, in a commercial gamma-gamma' nickel based superalloy. Such a configuration is very surprising, because there is apparently no reason for the coherency of such particles. PMID- 26806285 TI - Increased intake of vegetables, but not fruits, may be associated with reduced risk of hip fracture: A meta-analysis. AB - Association between dietary intake of vegetables and fruits and risk of hip fracture has been reported for many years. However, the findings remain inconclusive. We conducted a meta-analysis to evaluate the relationship between intake of vegetables and fruits, and risk of hip fracture. Literature search for relevant studies was performed on PubMed and Embase databases. Five observational studies were included in the meta-analysis. Summary hazard ratio (HR) with corresponding 95% confidence interval (CI) was calculated from pooled data using the random-effects model irrespective of heterogeneity. Sensitivity and subgroup analysis were performed to explore possible reasons for heterogeneity. The summary HR for hip fracture in relation to high intake vs. low intake of only vegetables, only fruits, and combined intake of fruits and vegetables, was 0.75 (95% CI, 0.61-0.92), 0.87 (95% CI, 0.74-1.04), and 0.79 (95% CI, 0.61-1.03), respectively. Subgroup analyses based on study design, geographical location, number of cases, and gender showed similar results. Increased intake of vegetables, but not fruits, was found to be associated with a lower risk of hip fracture. Large prospective clinical trials with robust methodology are required to confirm our findings. PMID- 26806287 TI - [Low sensibility to the action of thrombomodulin in cirrhotic patients. Interest of thrombinography]. AB - Cirrhosis is associated with complex hemostatic modifications. Most coagulation factors, either procoagulants or anticoagulants, are reduced. Conventional coagulation tests (prothrombin time, activated partial thromboplastin time) don't allow to precisely identify the thrombotic risk as they are not sensible to coagulation inhibitors deficiencies. The aim of this study was to evaluate the coagulation in a population of cirrhotic patients using thrombinography. We analyzed the plasma samples from 30 cirrhotic patients (10 Child A, 10 Child B, Child C 10) compared to 10 healthy controls using thrombinography with and without thrombomodulin to sensiblise this test at the activated protein C pathway. The results of endogenous thrombin potential, the main parameter, expressed as a ratio (thrombinography with/without thrombomodulin) were significantly higher in cirrhotic patients (0.69 +/- 0.16) than in controls (0.49 +/- 0.10) which reflects a low sensibility to the action of thrombomodulin. This resistance increases with the severity of the disease assessed by the Child-Pugh score, demonstrating a potential hypercoagulable state. The results of the thrombinography challenge the dogma that cirrhotic patients are naturally "anticoagulated." These results highlight the potential interest of the thrombinography in the detection and monitoring of hypercoagulability in cirrhotic patient. Increasing hypercoagulability with the severity of the disease seems to be correlated with clinical observations since the occurrence of thrombosis is more common when cirrhosis is at an advanced stage. PMID- 26806288 TI - Task complexity and location specific changes of cortical thickness in executive and salience networks after working memory training. AB - Novel activities and experiences shape the brain's structure and organisation and, hence, our behaviour. However, evidence from structural plasticity studies remains mixed and the neural correlates of learning and practice are still poorly understood. We conducted a robustly designed study into grey matter plasticity following 2 months of working memory training. We generated a priori hypotheses regarding the location of plastic effects across three cognitive control networks (executive, anterior salience and basal ganglia networks), and compared the effects of adaptive training (n=20) with a well-matched active control group (n=20) which differed in training complexity and included extensive cognitive assessment before and after the training. Adaptive training relative to control activities resulted in a complex pattern of subtle and localised structural changes: Training was associated with increases in cortical thickness in right lateralised executive regions, notably the right caudal middle frontal cortex, as well as increases in the volume of the left pallidum. In addition the training group showed reductions of thickness in the right insula, which were correlated with training-induced improvements in backward digit span performance. Unexpectedly, control activities were associated with reductions in thickness in the right pars triangularis. These results suggest that the direction of activity induced plastic changes depend on the level of training complexity as well as brain location. These observations are consistent with the view that the brain responds dynamically to environmental demands by focusing resources on task relevant networks and eliminating irrelevant processing for the purpose of energy reduction. PMID- 26806289 TI - Evaluating cognitive models of visual word recognition using fMRI: Effects of lexical and sublexical variables. AB - In this study predictions of the dual-route cascaded (DRC) model of word reading were tested using fMRI. Specifically, patterns of co-localization were investigated: (a) between pseudoword length effects and a pseudowords vs. fixation contrast, to reveal the sublexical grapho-phonemic conversion (GPC) system; and (b) between word frequency effects and a words vs. pseudowords contrast, to reveal the orthographic and phonological lexicon. Forty four native speakers of Greek were scanned at 3T in an event-related lexical decision task with three event types: (a) 150 words in which frequency, length, bigram and syllable frequency, neighborhood, and orthographic consistency were decorrelated; (b) 150 matched pseudowords; and (c) fixation. Whole-brain analysis failed to reveal the predicted co-localizations. Further analysis with participant-specific regions of interest defined within masks from the group contrasts revealed length effects in left inferior parietal cortex and frequency effects in the left middle temporal gyrus. These findings could be interpreted as partially consistent with the existence of the GPC system and phonological lexicon of the model, respectively. However, there was no evidence in support of an orthographic lexicon, weakening overall support for the model. The results are discussed with respect to the prospect of using neuroimaging in cognitive model evaluation. PMID- 26806290 TI - Representational dynamics of object recognition: Feedforward and feedback information flows. AB - Object perception involves a range of visual and cognitive processes, and is known to include both a feedfoward flow of information from early visual cortical areas to higher cortical areas, along with feedback from areas such as prefrontal cortex. Previous studies have found that low and high spatial frequency information regarding object identity may be processed over different timescales. Here we used the high temporal resolution of magnetoencephalography (MEG) combined with multivariate pattern analysis to measure information specifically related to object identity in peri-frontal and peri-occipital areas. Using stimuli closely matched in their low-level visual content, we found that activity in peri-occipital cortex could be used to decode object identity from ~80ms post stimulus onset, and activity in peri-frontal cortex could also be used to decode object identity from a later time (~265ms post stimulus onset). Low spatial frequency information related to object identity was present in the MEG signal at an earlier time than high spatial frequency information for peri-occipital cortex, but not for peri-frontal cortex. We additionally used Granger causality analysis to compare feedforward and feedback influences on representational content, and found evidence of both an early feedfoward flow and later feedback flow of information related to object identity. We discuss our findings in relation to existing theories of object processing and propose how the methods we use here could be used to address further questions of the neural substrates underlying object perception. PMID- 26806291 TI - Controlled ice nucleation--Is it really needed for large-volume sperm cryopreservation? AB - Controlled ice nucleation (CIN) is an integral stage of slow freezing process when relatively large volumes (usually 1 mL or larger) of biological samples in suspension are involved. Without it, a sample will supercool to way below its melting point before ice crystals start forming, resulting in multiple damaging processes. In this study, we tested the hypothesis that when freezing large volumes by the directional freezing technique, a CIN stage is not needed. Semen samples collected from ten bulls were frozen in 2.5-mL HollowTubes in a split sample manner with and without a CIN stage. Thawed samples were evaluated for viability, acrosome integrity, rate of normal morphology, and, using computer aided sperm analysis system, for a wide range of motility parameters that were also evaluated after 3 hours of incubation at 37 degrees C. Analysis of the results found no difference between freezing with and without CIN stage in any and all of the 29 parameters compared (P > 0.1 for all). This similarity was maintained through 3 hours of incubation at 37 degrees C. Possibly, because of its structure, the directional freezing device promotes continuous ice nucleation so a specific CIN stage is no longer needed, thus reducing costs, energy use, and carbon footprint. PMID- 26806292 TI - Dynamic epigenetic mechanisms regulate age-dependent SOX9 expression in mouse articular cartilage. AB - While the developmental role of the SOX9 transcription factor in chondrocyte differentiation and cartilage formation is well documented, age-dependent SOX9 expression in articular chondrocytes (ACs) and its regulatory mechanisms remain unclear. This study aimed to explore epigenetic regulatory mechanisms for age related changes in SOX9 expression in ACs of mice, spanning from the developmental stage to 18 months of age. Sox9 mRNA and protein were highly expressed in ACs during joint development but significantly decreased after 2 months of age. Histopathological features of osteoarthritis were not observed in examined hip and shoulder joints by 18 months of age. Epigenetic studies revealed that DNA methylation levels were increased at specific CpG islands of the Sox9 gene at 6 and 12 months; treatment of cultured ACs from 6-month-old mice with 5 azacytidine (an inhibitor of DNA methylation) elevated the level of Sox9 expression in ACs by lowering DNA methylation levels in the Sox9 promoter region. Histone 3 lysine 4 dimethylation (H3K4me2, a histone modification for transcriptional activation) in the Sox9 promoter region was decreased with age, which was associated with the age-dependent decrease in SOX9 expression in ACs. Knockdown of lysine-specific demethylase-1 up-regulated SOX9 expression in ACs of adult mice through increased recruitment of H3K4me2 in the Sox9 promoter region. Our results suggest that SOX9 expression in mouse ACs is significantly decreased after the completion of joint development. These age-dependent changes in SOX9 expression are dynamically regulated by DNA methylation and histone methylation. PMID- 26806293 TI - Global profiling of lysine acetylation in human histoplasmosis pathogen Histoplasma capsulatum. AB - Histoplasma capsulatum is the causative agent of human histoplasmosis, which can cause respiratory and systemic mycosis in immune-compromised individuals. Lysine acetylation, a protein posttranslational protein modification, is widespread in both eukaryotes and prokaryotes. Although increasing evidence suggests that lysine acetylation may play critical roles in fungus physiology, very little is known about its extent and function in H. capsulatum. To comprehensively profile protein lysine acetylation in H. capsulatum, we performed a global acetylome analysis through peptide prefractionation, antibody enrichment, and LC-MS/MS analysis, identifying 775 acetylation sites on 456 acetylated proteins; and functionally analysis showing their involvement in different biological processes. We defined six types of acetylation site motifs, and the results imply that lysine residue of polypeptide with tyrosine at the -1 and +1 positions, histidine at the +1 position, and phenylalanine (F) at the +1 and +2 position is a preferred substrate of lysine acetyltransferase. Moreover, some virulence factors candidates including calmodulin and DnaK are acetylated. In conclusion, our data set may serve as an important resource for the elucidation of associations between functional protein lysine acetylation and virulence in H. capsulatum. PMID- 26806294 TI - Assessment of mercury exposure in human populations: A status report from Augusta Bay (southern Italy). AB - Here we investigate mercury concentrations in the blood (HgB), urine (HgU) and human hair (HgH) of 224 individuals from a coastal area (Eastern Sicily, SE Italy) strongly affected by Hg contamination from one of the largest chlor-alkali plants in Europe. The factors affecting the distribution of Hg and the extent of the exposure of individuals have been explored with a multidisciplinary approach. Multiple regression analyses, together with evidence of high levels of HgB (exceeding the HBMI recommended levels in 50% of cases) and HgH (exceeding the EPA reference dose in 70% of cases), primarily suggest that the consumption of local fish is the main source of Hg for humans. no. significant exposure to inorganic mercury was identified. Toxicokinetic calculations produced a provisional tolerable weekly intake (PTWI) level that, in most cases, exceeds international recommendations, particularly for residents in the studied area. PMID- 26806295 TI - Over-expression of microRNA-375 inhibits papillary thyroid carcinoma cell proliferation and induces cell apoptosis by targeting ERBB2. AB - MicroRNAs (miRs) played important roles in the cell proliferation, apoptosis and other biological processes in cancer. In the present study we found that miR-375 was significantly down-regulated in human papillary thyroid carcinoma (PTC) tissues and cell lines. In this study we try to investigate the biological activity of miR-375 in human PTC cells and try to find the potential target of miR-375. Our study indicated that over-expression of miR-375 could inhibit the PTC cells proliferation and this inhibition was caused by the induction of cell apoptosis. In vivo animal study indicated that over-expression of miR-375 could significantly decrease the migration and invasion of human PTC cell in vivo. These results exhibit over-expression of miR-375 in human PTC cells could inhibit the process of human PTC. Further study demonstrated ERBB2 was a direct target of miR-375, over-expression of miR-375 decrease the both mRNA and protein expression of ERBB2 in human PTC cells. These data indicate miR-375 play important roles in the process and development of human PTC. These finds suggested that appropriate application of miR-375 regulation might be a new sight for the treatment of human PTC in the future. PMID- 26806296 TI - Perceptions of unmet needs for community social care services in England. A comparison of working carers and the people they care for. AB - Previous UK research has found expressed unmet need for services by unpaid working carers and among disabled and older people. There are, however, suggestions from research that views on unmet needs for services differ between carers and care-recipients. Working carers in the UK say that the care-recipient is sometimes reluctant to accept services and the few international comparative dyad studies that have been carried out find that carers perceive higher unmet need than care-recipients. Recent policy discussions in England have also recognised that there may be differences of opinion. We collected data in 2013 from working carer/care-recipient dyads in England about perceived need for services for the care-recipient, disability, unpaid care hour provision and individual and socio-demographic characteristics. We find that care-recipients as well as their carers perceive high unmet need for services, although carers perceive higher unmet need. For carers, unmet need is associated with the disability of the carer-recipient and being the daughter or son of the care recipient; for care-recipients it is associated with unpaid care hours, carers' employment status and carers' health. The majority of dyads agree on need for services, and agreement is higher when the working carer provides care for 10 hours or more hours a week. Services for care-recipients may enable working carers to remain in employment so agreement on needs for services supports the implementation of legislation, policy and practice that has a duty to, or aims to, support carer's employment. PMID- 26806298 TI - Genetic variants of CDH13 determine the susceptibility to chronic obstructive pulmonary disease in a Chinese population. AB - AIM: Adiponectin has been implicated in the development of chronic obstructive pulmonary disease (COPD). The CDH13 gene encodes T-cadherin that is an adiponectin receptor, and genetic variants of CDH13 determine blood adiponectin levels. The aim of this study was to investigate the effects of CDH13 variants on COPD susceptibility in a Chinese population. METHODS: Ten single-nucleotide polymorphisms (SNP) in CDH13 were screened using the SNaPshot method in 279 COPD patients and 367 control subjects. Association of genotypes or haplotypes constructed from these loci with COPD was analyzed in different genetic models. RESULTS: Among the 10 SNPs tested, rs4783244 and rs12922394 exhibited significant differences in allele or genotype frequencies between COPD patients and control subjects, whereas 8 other SNPs did not. The minor allele T was associated with decreased risk of COPD in the recessive model at rs4783244 (OR=0.42, P=0.023) and in the dominant model at rs12922394 (OR=0.70, P=0.022). The genotype TT at either rs4783244 or rs12922394 was associated with a significantly low level of plasma adiponectin when compared to genotypes GG and CC (P<0.05). Haplotypes GC in block 1 (rs4783244-rs12922394) as well as GTAC and ATGT in block 3 (rs4783266 rs11640522-rs11646849-rs11860282) significantly increased the risk of COPD, whereas haplotypes TT in block 1, TG in block 2 (rs11646011- rs11640875) and ATGC in block 3 were protective against COPD. CONCLUSION: CDH13 genetic variants determine Chinese individuals' susceptibility to COPD and thus are efficient genetic biomarkers for early detection of COPD. PMID- 26806299 TI - Berberine protects rat heart from ischemia/reperfusion injury via activating JAK2/STAT3 signaling and attenuating endoplasmic reticulum stress. AB - AIM: Berberine (BBR), an isoquinoline-derived alkaloid isolated from Rhizoma coptidis, exerts cardioprotective effects. Because endoplasmic reticulum (ER) stress plays a pivotal role in myocardial ischemia/reperfusion (MI/R)-induced apoptosis, it was interesting to examine whether the protective effects of BBR resulted from modulating ER stress levels during MI/R injury, and to define the signaling mechanisms in this process. METHODS: Male rats were treated with BBR (200 mg . kg(-1) . d(-1), ig) for 2 weeks, and then subjected to MI/R surgery. Cardiac dimensions and function were assessed using echocardiography. Myocardial infarct size and apoptosis was examined. Total serum LDH levels and CK activities, superoxide production, MDA levels and the antioxidant SOD activities in heart tissue were determined. An in vitro study was performed on cultured rat embryonic myocardium-derived cells H9C2 exposed to simulated ischemia/reperfusion (SIR). The expression of apoptotic, ER stress-related and signaling proteins were assessed using Western blot analyses. RESULTS: Pretreatment with BBR significantly reduced MI/R-induced myocardial infarct size, improved cardiac function, and suppressed myocardial apoptosis and oxidative damage. Furthermore, pretreatment with BBR suppressed MI/R-induced ER stress, evidenced by down regulating the phosphorylation levels of myocardial PERK and eIF2alpha and the expression of ATF4 and CHOP in heart tissues. Pretreatment with BBR also activated the JAK2/STAT3 signaling pathway in heart tissues, and co-treatment with AG490, a specific JAK2/STAT3 inhibitor, blocked not only the protective effects of BBR, but also the inhibition of BBR on MI/R-induced ER stress. In H9C2 cells, treatment with BBR (50 MUmol/L) markedly reduced SIR-induced cell apoptosis, oxidative stress and ER stress, which were abolished by transfection with JAK2 siRNA. CONCLUSION: BBR ameliorates MI/R injury in rats by activating the AK2/STAT3 signaling pathway and attenuating ER stress-induced apoptosis. PMID- 26806300 TI - DW10075, a novel selective and small-molecule inhibitor of VEGFR, exhibits antitumor activities both in vitro and in vivo. AB - AIM: Targeting the VEGF/VEGF receptor (VEGFR) pathway has proved to be an effective antiangiogenic approach for cancer treatment. Here, we identified 6-((2 ((3-acetamidophenyl)amino)pyrimidin-4-yl)oxy)-N-phenyl-1-naphthamide (designated herein as DW10075) as a novel and highly selective inhibitor of VEGFRs. METHODS: In vitro tyrosine kinase activity was measured using ELISA, and intracellular signaling pathway proteins were detected by Western blot analysis. Endothelial cell proliferation was examined with CCK-8 assays, and tumor cell proliferation was determined with SRB assays. Cell migration, tube formation and rat aortic ring assays were used to detect antiangiogenic activity. Antitumor efficacy was further evaluated in U87-MG human glioblastoma xenograft tumors in nude mice receiving DW10075 (500 mg . kg(-1) . d(-1), po) for two weeks. RESULTS: Among a panel of 21 kinases tested, DW10075 selectively inhibited VEGFR-1, VEGFR-2 and VEGFR-3 (the IC50 values were 6.4, 0.69 and 5.5 nmol/L, respectively), but did not affect 18 other kinases including FGFR and PDGFR at 10 MUmol/L. DW10075 significantly blocked VEGF-induced activation of VEGFR and its downstream signaling transduction in primary human umbilical vein endothelial cells (HUVECs), thus inhibited VEGF-induced HUVEC proliferation. DW10075 (1-100 nmol/L) dose-dependently inhibited VEGF-induced HUVEC migration and tube formation and suppressed angiogenesis in both the rat aortic ring model and the chicken chorioallantoic membrane model. Furthermore, DW10075 exhibited anti-proliferative activity against 22 different human cancer cell lines with IC50 values ranging from 2.2 MUmol/L (for U87-MG human glioblastoma cells) to 22.2 MUmol/L (for A375 melanoma cells). In U87-MG xenograft tumors in nude mice, oral administration of DW10075 significantly suppressed tumor growth, and reduced the expression of CD31 and Ki67 in the tumor tissues. CONCLUSION: DW10075 is a potent and highly selective inhibitor of VEGFR that deserves further development. PMID- 26806301 TI - Inhibition of hepatic cytochrome P450 enzymes and sodium/bile acid cotransporter exacerbates leflunomide-induced hepatotoxicity. AB - AIM: Leflunomide is an immunosuppressive agent marketed as a disease-modifying antirheumatic drug. But it causes severe side effects, including fatal hepatitis and liver failure. In this study we investigated the contributions of hepatic metabolism and transport of leflunomide and its major metabolite teriflunomide to leflunomide induced hepatotoxicity in vitro and in vivo. METHODS: The metabolism and toxicity of leflunomide and teriflunomide were evaluated in primary rat hepatocytes in vitro. Hepatic cytochrome P450 reductase null (HRN) mice were used to examine the PK profiling and hepatotoxicity of leflunomide in vivo. The expression and function of sodium/bile acid cotransporter (NTCP) were assessed in rat and human hepatocytes and NTCP-transfected HEK293 cells. After Male Sprague Dawley (SD) rats were administered teriflunomide (1,6, 12 mg . kg(-1) . d(-1), ig) for 4 weeks, their blood samples were analyzed. RESULTS: A nonspecific CYPs inhibitor aminobenzotriazole (ABT, 1 mmol/L) decreased the IC50 value of leflunomide in rat hepatocytes from 409 to 216 MUmol/L, whereas another nonspecific CYPs inhibitor proadifen (SKF, 30 MUmol/L) increased the cellular accumulation of leflunomide to 3.68-fold at 4 h. After oral dosing (15 mg/kg), the plasma exposure (AUC0-t) of leflunomide increased to 3-fold in HRN mice compared with wild type mice. Administration of leflunomide (25 mg.kg(-1) . d( 1)) for 7 d significantly increased serum ALT and AST levels in HRN mice; when the dose was increased to 50 mg.kg(-1) . d(-1), all HRN mice died on d 6. Teriflunomide significantly decreased the expression of NTCP in human hepatocytes, as well as the function of NTCP in rat hepatocytes and NTCP transfected HEK293 cells. Four-week administration of teriflunomide significantly increased serum total bilirubin and direct bilirubin levels in female rats, but not in male rats. CONCLUSION: Hepatic CYPs play a critical role in detoxification process of leflunomide, whereas the major metabolite teriflunomide suppresses the expression and function of NTCP, leading to potential cholestasis. PMID- 26806302 TI - Schisandrol B protects against acetaminophen-induced acute hepatotoxicity in mice via activation of the NRF2/ARE signaling pathway. AB - AIM: The nuclear factor erythroid 2-related factor 2 (NRF2) acts through the antioxidant response element (ARE) to regulate the expression of many detoxifying and antioxidant genes responsible for cytoprotective processes. We previously reported that Schisandrol B (SolB) isolated from Schisandra sphenanthera produced a protective effect against acetaminophen (APAP)-induced liver injury. In this study we investigated whether the NRF2/ARE signaling pathway was involved in this hepato-protective effect. METHODS: Male C57BL/6 mice were treated with SolB (200 mg . kg(-1) . d(-1), ig) for 3 d before injection of APAP (400 mg/kg, ip). Serum and liver tissue samples were collected 6 h later. The mRNA and protein expression were measured using qRT-PCR and Western blot assay, respectively. The activation of NRF2 was examined in HepG2 cells using luciferase reporter gene assay. RESULTS: SolB pretreatment significantly alleviated the hepatic injury (large patchy necrosis and hyperemia of the hepatic sinus), the increase of serum AST, ALT levels and hepatic MDA contents, and the decrease of liver and mitochondrial glutathione levels in APAP-treated mice. Furthermore, SolB pretreatment significantly increased nuclear accumulation of NRF2 and increased hepatic expression of NRF2 downstream proteins, including GCLC, GSR, NQO1, GSTs, MRP2, MRP3 and MRP4 in APAP-treated mice. Moreover, treatment with SolB (2.5-20 MUmol/L) dose-dependently increased the activity of NRF2 reporter gene in HepG2 cells. CONCLUSION: SolB exhibits a remarkable protective effect against APAP induced hepatotoxicity, partially via activation of the NRF2/ARE pathway and regulation of NRF2 target genes, which induce detoxification and increase antioxidant capacity. PMID- 26806303 TI - Eukaryotic elongation factor 2 kinase as a drug target in cancer, and in cardiovascular and neurodegenerative diseases. AB - Eukaryotic elongation factor 2 kinase (eEF2K) is an unusual protein kinase that regulates the elongation stage of protein synthesis by phosphorylating and inhibiting its only known substrate, eEF2. Elongation is a highly energy consuming process, and eEF2K activity is tightly regulated by several signaling pathways. Regulating translation elongation can modulate the cellular energy demand and may also control the expression of specific proteins. Growing evidence links eEF2K to a range of human diseases, including cardiovascular conditions (atherosclerosis, via macrophage survival) and pulmonary arterial hypertension, as well as solid tumors, where eEF2K appears to play contrasting roles depending on tumor type and stage. eEF2K is also involved in neurological disorders and may be a valuable target in treating depression and certain neurodegenerative diseases. Because eEF2K is not required for mammalian development or cell viability, inhibiting its function may not elicit serious side effects, while the fact that it is an atypical kinase and quite distinct from the vast majority of other mammalian kinases suggests the possibility to develop it into compounds that inhibit eEF2K without affecting other important protein kinases. Further research is needed to explore these possibilities and there is an urgent need to identify and characterize potent and specific small-molecule inhibitors of eEF2K. In this article we review the recent evidence concerning the role of eEF2K in human diseases as well as the progress in developing small-molecule inhibitors of this enzyme. PMID- 26806304 TI - Differential modulation of GABAA and NMDA receptors by alpha7-nicotinic receptor desensitization in cultured rat hippocampal neurons. AB - AIM: To explore the modulatory effect of desensitized alpha7-containing nicotinic receptors (alpha7-nAChRs) on excitatory and inhibitory amino acid receptors in cultured hippocampal neurons and to identify the mechanism underlying this effect. METHODS: Whole-cell patch-clamp recordings were performed on cultured rat hippocampal neurons to measure alpha7-nAChR currents and to determine the role of desensitized alpha7-nAChRs on brain amino acid receptor activity. RESULTS: Pulse and perfusion applications of the alpha7-nAChR agonist choline were applied to induce different types of alpha7-nAChR desensitization in cultured hippocampal neurons. After a brief choline pulse, alpha7-nAChR was desensitized as a result of receptor activation, which reduced the response of the A type gamma aminobutyric acid (GABAA) receptor to its agonist, muscimol, and enhanced the response of the NMDA receptor to its agonist NMDA. By contrast, the responses of glycine or AMPA receptors to their agonists, glycine or AMPA, respectively, were not affected. Pretreatment with the alpha7-nAChR antagonist methyllycaconitine (MLA, 10 nmol/L) blocked the choline-induced negative modulation of the GABAA receptor and the positive modulation of the NMDA receptor. The regulation of the GABAA and NMDA receptors was confirmed using another type of alpha7-nAChR desensitization, which was produced by a low concentration of choline perfusion. The negative modulation of the GABAA receptor was characterized by choline duration dependency and intracellular calcium dependency, but the positive modulation of the NMDA receptor was not associated with cytoplasmic calcium. CONCLUSION: Brain GABAA and NMDA receptors are modulated negatively and positively, respectively, by desensitized alpha7-nAChR as a result of choline pretreatment in cultured hippocampal neurons. PMID- 26806306 TI - MD-2 binds cholesterol. AB - Cholesterol is a structural component of cellular membranes, which is transported from liver to peripheral cells in the form of cholesterol esters (CE), residing in the hydrophobic core of low-density lipoprotein. Oxidized CE (OxCE) is often found in plasma and in atherosclerotic lesions of subjects with cardiovascular disease. Our earlier studies have demonstrated that OxCE activates inflammatory responses in macrophages via toll-like receptor-4 (TLR4). Here we demonstrate that cholesterol binds to myeloid differentiation-2 (MD-2), a TLR4 ancillary molecule, which is a binding receptor for bacterial lipopolysaccharide (LPS) and is indispensable for LPS-induced TLR4 dimerization and signaling. Cholesterol binding to MD-2 was competed by LPS and by OxCE-modified BSA. Furthermore, soluble MD-2 in human plasma and MD-2 in mouse atherosclerotic lesions carried cholesterol, the finding supporting the biological significance of MD-2 cholesterol binding. These results help understand the molecular basis of TLR4 activation by OxCE and mechanisms of chronic inflammation in atherosclerosis. PMID- 26806307 TI - LncRNA-HOTAIR promotes TNF-alpha production in cardiomyocytes of LPS-induced sepsis mice by activating NF-kappaB pathway. AB - BACKGROUND: Mounting studies have illustrated an important role of HOTAIR in cancer progress, but few studies have reported its function in cardiac disease, including cardiac-associated sepsis. This study aimed to investigate the function of HOTAIR in sepsis, involving its association with the level of tumor necrosis factor-alpha (TNF-alpha), an important inducer of myocardial dysfunction during LPS-induced sepsis. METHODS: Sepsis mice model was established by LPS administration, and myocardial dysfunction was evaluated with hemodynamic parameters. HOTAIR expression in isolated cardiomyocytes and TNF-alpha production in the circulation were detected, as well as the protein levels of phosphorylated p65. HL-1 cells were subjected to LPS treatment in vitro for functional studies, including luciferase report assays for NF-kappaB activity. RESULTS: HOTAIR expression was significantly upregulated in cardiomyocytes from sepsis mice, in line with increased TNF-alpha production and p65 phosphorylation, while similar results were also observed in LPS treated HL-1 cells, which was then reversed by HOTAIR interference. Functional studies demonstrated that HOTAIR showed positive regulation on p65 phosphorylation and NF-kappaB activation, while HOTAIR-induced TNF-alpha production was repressed by NF-kappaB inhibitor. Further in vivo studies confirmed that HOTAIR silence can improve cardiac function of sepsis mice, and markedly decreased TNF-alpha production in the circulation. CONCLUSION: HOTAIR upregulation in cardiomyocytes of LPS-induced sepsis mice promoted TNF alpha production in the circulation by activating NF-kappaB, involving the phosphorylation of NF-kappaB p65 subunit. Moreover, HOTAIR silence preserved cardiac function of sepsis mice during LPS-induced sepsis. PMID- 26806305 TI - Pharmacokinetics and pharmacodynamics of SCT800, a new recombinant FVIII, in hemophilia A mice. AB - AIM: SCT800 is a new third-generation recombinant FVIII agent that is undergoing promising preclinical study. This study aimed to investigate the pharmacokinetic and pharmacodynamic profiles of SCT800 in hemophilia A mice. METHODS: After hemophilia A mice were intravenously injected with single dose of SCT800 (80, 180, and 280 IU/kg) or the commercially available product Xyntha (280 IU/kg), pharmacokinetics profiles were evaluated based on measuring plasma FVIII: C. For pharmacodynamics study, dose-response curves of SCT800 and Xyntha (1-200 IU/kg) were constructed using a tail bleeding model monitoring both bleeding time and blood loss. RESULTS: Pharmacokinetics profile analysis showed a dose independency of SCT800 ranging from 80 to 280 IU/kg and comparable pharmacokinetic profiles between SCT800 and Xyntha at the doses tested. Pharmacodynamics study revealed comparable ED50 values of SCT800 and Xyntha in the tail bleeding model: 14.78 and 15.81 IU/kg for bleeding time, respectively; 13.50 and 13.58 IU/kg for blood loss, respectively. Moreover, at the doses tested, the accompanying dose-related safety evaluation in the tail bleeding model showed lower hypercoagulable tendency and wider dosage range potential for SCT800 than Xyntha. CONCLUSION: In hemophilia A mice, SCT800 shows comparable pharmacokinetics and pharmacodynamics to Xyntha at the doses tested, and possibly with better safety properties. PMID- 26806308 TI - miR-625 suppresses cell proliferation and migration by targeting HMGA1 in breast cancer. AB - Dysregulation of microRNA contributes to the high incidence and mortality of breast cancer. Here, we show that miR-625 was frequently down-regulated in breast cancer. Decrease of miR-625 was closely associated with estrogen receptor (P = 0.004), human epidermal growth factor receptor 2 (P = 0.003) and clinical stage (P = 0.001). Kaplan-Meier and multivariate analyses indicated miR-625 as an independent factor for unfavorable prognosis (hazard ratio = 2.654, 95% confident interval: 1.300-5.382, P = 0.007). Re-expression of miR-625 impeded, whereas knockdown of miR-625 enhanced cell viabilities and migration abilities in breast cancer cells. HMGA1 was confirmed as a direct target of miR-625. The expressions of HMGA1 mRNA and protein were induced by miR-625 mimics, but reduced by miR-625 inhibitor. Re-introduction of HMGA1 in cells expressing miR-625 distinctly abrogated miR-625-mediated inhibition of cell growth. Taken together, our data demonstrate that miR-625 suppresses cell proliferation and migration by targeting HMGA1 and suggest miR-625 as a promising prognostic biomarker and a potential therapeutic target for breast cancer. PMID- 26806309 TI - Local fibroblast proliferation but not influx is responsible for synovial hyperplasia in a murine model of rheumatoid arthritis. AB - Synovial fibroblasts play crucial roles in inflammation and joint destruction in rheumatoid arthritis (RA). How they accumulate in the RA joints remains unclear. This study was conducted to discern whether cellular influx from the outside of the joints and local proliferation are responsible for synovial fibroblast accumulation in an animal model of RA. We found that synovial fibroblasts were identified as GFP+ cells using collagen type I alpha 2 (Col1a2)-GFP transgenic reporter mice. Then, bone marrow transplantation and parabiosis techniques were utilized to study the cellular influx. Irradiated wild-type mice were transplanted with bone marrow from Col1a2-GFP mice. Col1a2-GFP and wild-type mice were conjoined for parabiosis. The transplanted mice and the parabionts were subjected to collagen antibody-induced arthritis (CAIA). We found no GFP+ cells in the hyperplastic synovial tissues from the transplanted mice with CAIA and from the wild-type parabionts with CAIA. Furthermore, normal and CAIA synovial tissues from Col1a2-GFP mice and from fluorescent ubiquitination-based cell cycle indicator (Fucci) transgenic mice, in which cells in S/G2/M phases of the cell cycle express Azami-Green, were studied for Ki67, a cellular proliferation marker, and vimentin, a fibroblast marker, expression. The percentages of Ki67+/GFP+ and Azami-Green+/vimentin+ cells in the CAIA synovial tissues were higher than those in the untreated synovial tissues (34% vs. 0.40% and 19% vs. 0.26%, respectively). These findings indicate that local fibroblast proliferation but not cellular influx is responsible for the synovial hyperplasia in CAIA. Suppression of proliferation of the local synovial fibroblasts should be a promising treatment for RA. PMID- 26806310 TI - Usability of the Massachusetts Prescription Drug Monitoring Program in the Emergency Department: A Mixed-methods Study. AB - OBJECTIVES: Prescription drug monitoring programs (PDMPs) are underutilized, despite evidence showing that they may reduce the epidemic of opioid-related addiction, diversion, and overdose. We evaluated the usability of the Massachusetts (MA) PDMP by emergency medicine providers (EPs), as a system's usability may affect how often it is used. METHODS: This was a mixed-methods study of 17 EPs. We compared the time and number of clicks required to review one patient's record in the PDMP to three other commonly performed computer-based tasks in the emergency department (ED: ordering a computed tomography [CT] scan, writing a prescription, and searching a medication history service integrated within the electronic medical record [EMR]). We performed semistructured interviews and analyzed participant comments and responses regarding their experience using the MA PDMP. RESULTS: The PDMP task took a longer time to complete (mean = 4.22 minutes) and greater number of mouse clicks to complete (mean = 50.3 clicks) than the three other tasks (CT-pulmonary embolism = 1.42 minutes, 24.8 clicks; prescription = 1.30 minutes, 19.5 clicks; SureScripts = 1.45 minutes, 9.5 clicks). Qualitative analysis yielded four main themes about PDMP usability, three negative and one positive: 1) difficulty accessing the PDMP, 2) cumbersome acquiring patient medication history information within the PDMP, 3) nonintuitive display of patient medication history information within the PDMP, and 4) overall perceived value of the PDMP despite an inefficient interface. CONCLUSIONS: The complicated processes of gaining access to, logging in, and using the MA PDMP are barriers to preventing its more frequent use. All states should evaluate the PDMP usability in multiple practice settings including the ED and work to improve provider enrollment, login procedures, patient information input, prescription data display, and ultimately, PDMP data integration into EMRs. PMID- 26806311 TI - General Base-General Acid Catalysis in Human Histone Deacetylase 8. AB - Histone deacetylases (HDACs) regulate cellular processes such as differentiation and apoptosis and are targeted by anticancer therapeutics in development and in the clinic. HDAC8 is a metal-dependent class I HDAC and is proposed to use a general acid-base catalytic pair in the mechanism of amide bond hydrolysis. Here, we report site-directed mutagenesis and enzymological measurements to elucidate the catalytic mechanism of HDAC8. Specifically, we focus on the catalytic function of Y306 and the histidine-aspartate dyads H142-D176 and H143-D183. Additionally, we report X-ray crystal structures of four representative HDAC8 mutants: D176N, D176N/Y306F, D176A/Y306F, and H142A/Y306F. These structures provide a useful framework for understanding enzymological measurements. The pH dependence of kcat/KM for wild-type Co(II)-HDAC8 is bell-shaped with two pKa values of 7.4 and 10.0. The upper pKa reflects the ionization of the metal-bound water molecule and shifts to 9.1 in Zn(II)-HDAC8. The H142A mutant has activity 230-fold lower than that of wild-type HDAC8, but the pKa1 value is not altered. Y306F HDAC8 is 150-fold less active than the wild-type enzyme; crystal structures show that Y306 hydrogen bonds with the zinc-bound substrate carbonyl, poised for transition state stabilization. The H143A and H142A/H143A mutants exhibit activity that is >80000-fold lower than that of wild-type HDAC8; the buried D176N and D176A mutants have significant catalytic effects, with more subtle effects caused by D183N and D183A. These enzymological and structural studies strongly suggest that H143 functions as a single general base-general acid catalyst, while H142 remains positively charged and serves as an electrostatic catalyst for transition state stabilization. PMID- 26806313 TI - Quality of interactions influences everyday life in psychiatric inpatient care- patients' perspectives. AB - Everyday life consists of daily activities that are taken for granted. It forms the foundation for human efforts and contains elements of both comfort and boredom. Because everyday life escapes no one, life in a psychiatric ward will become ordinary while staying there. This study aims to explore everyday life in psychiatric inpatient care based on patients' experiences. We individually interviewed 16 participants with experiences of psychiatric inpatient care and analysed the data in accordance with the methods of grounded theory. Data collection and analysis continued in parallel in accordance with the method. Our results showed that everyday life is linked to the core category quality of interactions influences everyday life, and three constructed categories-staff makes the difference, looking for shelter in a stigmatizing environment, and facing a confusing care content-were related to the core category. Our results highlight the importance of ordinary relationships between staff and patients in psychiatric inpatient care. These results can be used to develop nursing interventions to improve psychiatric inpatient care and might also be used as a basis for reflective dialogues among staff. PMID- 26806314 TI - Stimuli-responsive dendrimers in drug delivery. AB - Dendrimers have shown great promise as carriers in drug delivery due to their unique structures and superior properties. However, the precise control of payload release from a dendrimer matrix still presents a great challenge. Stimuli responsive dendrimers that release payloads in response to a specific trigger could offer distinct clinical advantages over those dendrimers that release payloads passively. These smart polymers are designed to specifically release their payloads at targeted regions or at constant release profiles for specific therapies. They represent an attractive alternative to targeted dendrimers and enable dendrimer-based therapeutics to be more effective, more convenient, and much safer. The wide range of stimuli, either endogenous (acid, enzyme, and redox potentials) or exogenous (light, ultrasound, and temperature change), allows great flexibility in the design of stimuli-responsive dendrimers. In this review article, we will highlight recent advances and opportunities in the development of stimuli-responsive dendrimers for the treatment of various diseases, with emphasis on cancer. Specifically, the applications of stimuli-responsive dendrimers in drug delivery as well as their mechanisms are intensively reviewed. PMID- 26806315 TI - How health navigators legitimize the Affordable Care Act to the uninsured poor. AB - Health navigators are a new health care workforce created by the Affordable Care Act (ACA) to assist low-income minority populations with acquiring health insurance. Given the high levels of distrust among the poor toward government and the medical profession, this article asks: How do health navigators build the legitimacy necessary to persuade low-income uninsured clients to enroll in health insurance? Through ethnography of face-to-face interaction between navigators and the uninsured poor in Chicago, this study shows that successful navigators deployed a combination of cultural repertoires for building trust and legitimacy. These repertoires included ceding control of the conversation, creating ethnic solidarity, and disassociating themselves from government bureaucrats or self serving insurance employees. These findings demonstrate the usefulness of cultural sociology for understanding health insurance provision to the poor, ACA outreach efforts, and the more general study of how occupations legitimize themselves to clients. PMID- 26806317 TI - Predicting Which Patients will Likely Benefit from Subglottic Secretion Drainage Endotracheal Tubes: A Retrospective Study. AB - BACKGROUND: Subglottic secretion drainage endotracheal tubes (SSD ETTs) have been shown to decrease ventilator-associated pneumonia and are recommended for patients intubated > 48 h or 72 h. However, it is difficult to determine which patients will be intubated > 48 h or 72 h at the time of intubation. OBJECTIVE: We attempted to determine which patient characteristics were associated with intubations >= 48 h or 72 h in order to guide proper placement of SSD ETTs. METHODS: The medical records of 2,159 ventilated patients at a single institution were retrospectively reviewed for intubation duration, age, sex, race, body mass index, weight, intubation reason, whether the intubation was emergent, operative status, intensive care unit (ICU) diagnosis, intubation location, ICU location, comorbidities (e.g., congestive heart failure, chronic obstructive pulmonary disorder, coronary artery disease, dementia, and liver disease), acute kidney injury (AKI), and chronic renal injury. A multivariate regression analysis was then performed with all reliable data. RESULTS: The following were associated with intubation >= 48 h: neuroscience critical care unit (NCCU) admission (risk ratio [RR] = 1.85; 95% confidence interval [CI] 1.34-2.56), emergent intubation (RR = 1.97; 95% 1.28-3.03), comorbid dementia (RR = 2.31; 95% 1.28-4.18), nonoperative intubation (RR = 1.77; 95% 1.28-4.18), and AKI (RR = 3.32; 95% 2.56 4.3). The following were independently associated with intubation >= 72 h: NCCU admission (RR = 2.2; 95 CI 1.57-3.08), nonoperative intubation (RR = 3.38; 95% CI 2.63-4.35), comorbid dementia (RR = 3.03; 95% CI 1.67-5.48), and AKI (RR = 3.11; 95% CI 2.38-4.07). CONCLUSION: Nonoperative intubation, emergent intubation, history of dementia, admission to NCCU and AKI all appear to be independently associated with increased RRs for either >= 48 h or 72 h of ventilation. PMID- 26806316 TI - Metabolic engineering of proanthocyanidin production by repressing the isoflavone pathways and redirecting anthocyanidin precursor flux in legume. AB - MtPAR is a proanthocyanidin (PA) biosynthesis regulator; the mechanism underlying its promotion of PA biosynthesis is not fully understood. Here, we showed that MtPAR promotes PA production by a direct repression of biosynthesis of isoflavones, the major flavonoids in legume, and by redirecting immediate precursors, such as anthocyanidins, flux into PA pathway. Ectopic expression of MtPAR repressed isoflavonoid production by directly binding and suppressing isoflavone biosynthetic genes such as isoflavone synthase (IFS). Meanwhile, MtPAR up-regulated PA-specific genes and decreased the anthocyanin levels without altering the expression of anthocyanin biosynthetic genes. MtPAR may shift the anthocyanidin precursor flux from anthocyanin pathway to PA biosynthesis. MtPAR complemented PA-deficient phenotype of Arabidopsis tt2 mutant seeds, demonstrating their similar action on PA production. We showed the direct interactions between MtPAR, MtTT8 and MtWD40-1 proteins from Medicago truncatula and Glycine max, to form a ternary complex to trans-activate PA-specific ANR gene. Finally, MtPAR expression in alfalfa (Medicago sativa) hairy roots and whole plants only promoted the production of small amount of PAs, which was significantly enhanced by co-expression of MtPAR and MtLAP1. Transcriptomic and metabolite profiling showed an additive effect between MtPAR and MtLAP1 on the production of PAs, supporting that efficient PA production requires more anthocyanidin precursors. This study provides new insights into the role and mechanism of MtPAR in partitioning precursors from isoflavone and anthocyanin pathways into PA pathways for a specific promotion of PA production. Based on this, a strategy by combining MtPAR and MtLAP1 co-expression to effectively improve metabolic engineering performance of PA production in legume forage was developed. PMID- 26806318 TI - Impact of Video Discharge Instructions for Pediatric Fever and Closed Head Injury from the Emergency Department. AB - BACKGROUND: Lack of understanding of diagnosis and disease process remains a major complaint of caregivers who bring their children to the pediatric emergency department (PED). Misunderstanding of diagnosis and discharge instructions can lead to unnecessary return visits and health disparities. OBJECTIVE: We attempted to determine if video discharge instructions when added to standard of care written and verbal instruction improved caregivers' comprehension of their child's diagnosis, disease process, and discharge instructions. METHODS: Caregivers who presented to the PED with a child's chief complaint of fever or closed head injury (CHI) were included and randomized into a control or intervention group. Each group received standard discharge instructions, and the intervention group additionally viewed a video. Participants completed a post test on knowledge and were followed 2 weeks post-visit to determine follow-up care. RESULTS: Sixty-three caregivers participated in the study. Eleven participants had less than a high school (HS) education and 52 had more than a HS education. Thirty-one children presented with fever and 32 with CHI. The intervention group had significantly higher percentage of correct answers on postintervention tests (median [Mdn] = 88.89) than the control (Mdn = 75.73; p < 0.0001). Participants in the intervention group with less than a HS education (Mdn = 89.47) and more than HS education (Mdn = 88.89) had similar test scores (p = 0.13), whereas those in the control group with less than a HS education (Mdn = 66.67) had significantly lower test scores than those with more than a HS education (Mdn = 77.78; p = 0.03). CONCLUSION: For caregivers with children who presented to the PED with fever and CHI, video discharge instructions improved caregiver comprehension of the child's diagnosis and disease process when added to verbal and written instructions. PMID- 26806319 TI - The Use of Internal Jugular Vein Ultrasonography to Anticipate Low or High Central Venous Pressure During Mechanical Ventilation. AB - BACKGROUND: Critically low or high central venous pressure (CVP) values, together with systemic hypotension, can indicate hypovolemia or acute heart failure. However, measuring CVP requires the insertion of a central venous catheter, a time-consuming procedure that can be associated with severe complications. OBJECTIVE: We sought to evaluate the use of ultrasonography of the internal jugular vein (IJV) to estimate low or high CVP values in patients who were on ventilation. METHODS: Ultrasonography of IJV dimensions and the collection of hemodynamic data was performed in 47 patients, and the ratio between IJV diameter in the 30 degrees and 0 degrees position was calculated (ratio(30/0)). The predictive value of ratio(30/0) for estimating low and high CVP levels was analyzed using receiver operating characteristic curves. RESULTS: The median IJV diameter ratio(30/0) was 0.49. CVP ranged from 1 to 13 mm Hg (median 7 mm Hg). Seventeen patients had a CVP <= 5 mm Hg or lower (defined as "low"), and in 11 patients, values of >= 10 mm Hg were measured (defined as "high"). The corresponding IJV diameter ratios increased significantly from 0.34 (in the low CVP group) to 0.9 (in the high CVP group). Receiver operating characteristic analysis revealed a good predictive value of the ratio(30/0) for the prediction of low or high CVP values, respectively. A ratio(30/0) of < 0.45 optimally indicated a low CVP, while > 0.65 was the cutoff value to detect a CVP >= 10 mm Hg. CONCLUSION: The estimation of low or high CVP values by IJV ultrasonography in different patient positions can be a helpful instrument for the rapid hemodynamic assessment of the critically ill patient. PMID- 26806320 TI - Lung cancer: Resolving resistance to ALK-targeted therapy. PMID- 26806321 TI - Photon Cascade from a Single Crystal Phase Nanowire Quantum Dot. AB - We report the first comprehensive experimental and theoretical study of the optical properties of single crystal phase quantum dots in InP nanowires. Crystal phase quantum dots are defined by a transition in the crystallographic lattice between zinc blende and wurtzite segments and therefore offer unprecedented potential to be controlled with atomic layer accuracy without random alloying. We show for the first time that crystal phase quantum dots are a source of pure single-photons and cascaded photon-pairs from type II transitions with excellent optical properties in terms of intensity and line width. We notice that the emission spectra consist often of two peaks close in energy, which we explain with a comprehensive theory showing that the symmetry of the system plays a crucial role for the hole levels forming hybridized orbitals. Our results state that crystal phase quantum dots have promising quantum optical properties for single photon application and quantum optics. PMID- 26806322 TI - Effects of focal/grid laser treatment on the central visual field in diabetic macular oedema: a 2-year follow-up study. AB - PURPOSE: To assess the long-term effects of focal/grid laser treatment on the central visual field in subjects with clinically significant diabetic macular oedema (CSMO). METHODS: Twenty-six subjects with CSMO were included in the study. Fundus photography, assessment of retinal thickness by time-domain optical coherence tomography (OCT), measurement of visual acuity (VA) and standard automated perimetry of the central 10 degrees of the visual field were performed at baseline before focal/grid laser treatment and thereafter at four follow-up visits 6 months apart, when the laser treatment was also repeated in subjects with persistent oedema. Changes in VA and retinal thickness between baseline and study end at 24-month follow-up were calculated. Trends in changes in the visual field were assessed by linear regression of number of significantly depressed test points over time. RESULTS: On average after the laser treatment, retinal thickness decreased by 17% and VA decreased by three letters. In most eyes, visual fields were stable over time: the mean of the trend slopes (0.05 points/month) did not differ significantly from 0 (p = 0.63). The number of depressed test points at follow-up was not correlated with either the total number of laser effects or the number of laser sessions. CONCLUSION: Focal/grid laser treatment for CSMO did not affect retinal sensitivity in the central visual field in the subjects included in this 2-year follow-up study. PMID- 26806323 TI - The combination of a novel 2 bp deletion mutation and p.D63H in CYP11B1 cause congenital adrenal hyperplasia due to steroid 11beta-hydroxylase deficiency. AB - Deficiency of steroid 11beta-hydroxylase activity occurs in 5-8% of patients with congenital adrenal hyperplasia (CAH). The aim of the current study was to identify mutations in the CYP11B1 gene of a patient with CAH due to deficiency of steroid 11beta-hydroxylase activity, and to study the functional and structural consequences of these mutations. A molecular genetic analysis of the CYP11B1 gene in this patient and her parents identified a known missense mutation g.5194G>C (p.D63H) and a novel 2 bp deletion mutation (g.9525_9526delCT, corresponding to p.L380V...R420X) in the patient. In vitro expression studies in COS7 cells revealed a decreased 11beta-hydroxylase activity in the p.D63H mutant to 2.0+/ 0.8% and in the p.L380V...R420X mutant to 0.2+/-2.2% for the conversion of 11 deoxycortisol to cortisol. Three dimensional homology models for the normal and mutant proteins were built by using the recently published x-ray structure of the human CYP11B2 as a template. Presumably, the g.9525_9526delCT mutation in CYP11B1 resulted in a truncated protein with a misfolded C-terminal domain that could not efficiently bind heme iron, substrate, and adrenodoxin and had lost its biochemical function. In summary, CAH due to steroid 11beta-hydroxylase deficiency can be attributed to both the novel deletion mutation (g.9525_9526delCT, corresponding to p.L380V...R420X) and known missense mutation (g.5194G>C corresponding to p.D63H) in CYP11B1. PMID- 26806325 TI - Genome-wide identification and characterization of Eutrema salsugineum microRNAs for salt tolerance. AB - Eutrema salsugineum, a close relative of Arabidopsis thaliana, is a valuable halophytic model plant that has extreme tolerance to salinity. As posttranscriptional gene regulators, microRNAs (miRNAs) control gene expression and a variety of biological processes, including plant-stress responses. To identify salt-stress responsive miRNAs in E. salsugineum and reveal their possible roles in the adaptive response to salt stress, we chose the Solexa sequencing platform to screen the miRNAs in 4-week-old E. salsugineum seedlings under salt treatment. A total of 82 conserved miRNAs belonging to 27 miRNA families and 17 novel miRNAs were identified and 11 conserved miRNA families and 4 novel miRNAs showed a significant response to salt stress. To investigate the possible biological roles of miRNAs, 1060 potential targets were predicted. Moreover, 35 gene ontology (GO) categories and 1 pathway, including a few terms that were directly and indirectly related to salt stress, were significantly enriched in the salt-stress-responsive miRNAs targets. The relative expression analysis of six target genes was analyzed using quantitative real-time polymerase chain reaction (PCR) and showed a negative correlation with their corresponding miRNAs. Many stress regulatory and phytohormone regulatory cis-regulatory elements were widely present in the promoter region of the salt-responsive miRNA precursors. This study describes the large-scale characterization of E. salsugineum miRNAs and provides a useful resource for further understanding of miRNA functions in the regulation of the E. salsugineum salt-stress response. PMID- 26806326 TI - Lipid peroxidation is associated with poor control of type-2 diabetes mellitus. AB - BACKGROUND: Hyperglycemia increases oxidative stress through the overproduction of reactive oxygen species, which results in an imbalance between free radicals and the antioxidant defense system of the cells. A positive correlation was reported between lipid peroxide levels and diabetic complication. OBJECTIVES: The aim of the present study was to investigate the state of oxidative stress in controlled and uncontrolled diabetic patients. METHODS: One hundred thirty nine participants were included in this study, grouped as: Group-I: Healthy Control group of non-diabetic normal subjects, Group-II: Controlled type-2 DM group of subjects with type-2 DM and HbA1c<=8% and Group-III: Uncontrolled type-2 DM group of subjects with type-2 DM and HbA1c>8%. Fasting blood glucose, 2h postprandial glucose, MDA and HbA1c were quantified. The association between diabetic control and lipid peroxidation (malondialdehyde) was evaluated. RESULTS: The mean HbA1c increased significantly in uncontrolled type-2 DM subjects compared to controlled type-2 DM group. Lipid peroxidation as expressed in MDA was significantly increased in uncontrolled type-2 DM group compared to controlled type-2 DM, both groups show significant elevation in this parameter compared to healthy subjects. There is a significant positive correlation between MDA and HbA1c in the studied subjects. CONCLUSION: The core problem during diabetes is poor glycemic control, which leads to protein glycation, lipid peroxidation, oxidative stress and finally varieties of complications. Periodic evaluation of lipid peroxidation products in diabetes mellitus is recommended as it could contribute to the early identification and management of oxidative stress. PMID- 26806327 TI - Incidence and risk factors of hypoglycemia among Type 2 diabetic patients in a South Indian hospital. AB - AIM: The study was aimed at assessing the cumulative incidence of hypoglycemia and precipitating risk factors among type 2 diabetes mellitus in-patients of a tertiary care hospital in South India. METHODS: The prospective cross sectional study spanning 14 months was conducted in a tertiary care hospital in Kerala. All T2DM patients who were administered any form of insulin during the length of hospital stay was monitored for assessing the hypoglycemic episodes. Any patient with a GRBS value less than 70mg/dL was defined to be hypoglycemic as per the ADA guidelines. The statistical analysis of collected data was performed using SPSS 18 for windows version. RESULTS: Of the 1650 subjects enrolled in the study, 204 subjects developed hypoglycemia. The sample composed of 60.8% females and 39.2% males and the difference was significant with p=0.02. A significant positive correlation was observed between HbA1c values and GRBS value, with a 2 tailed Pearson correlation coefficient of 0.027. On stratifying as per the modality of insulin dose prescribed, 72.5% of the hypoglycemic patients were found to have been administered fixed dose insulin. CONCLUSION: The cumulative incidence of institutional hypoglycemia among type 2 diabetic inpatients was gauged as 12.36%; among which, 26.96% had asymptomatic episodes. PMID- 26806328 TI - Biological activities of unique isoflavones prepared from Apios americana Medik. AB - Four unique isoflavone aglycones (barpisoflavone A (1), 2'-hydroxygenistein (2), 5-methylgenistein (3), and gerontoisoflavone A (4)) whose structures were related to genistein were prepared from the tuber of Apios americana Medik. We examined the estrogen receptor and androgen receptor binding activities, estrogen agonistic activities, antioxidant activities, and alpha-glucosidase inhibitory activities of 1-4. The results obtained showed that 2 possessed potent and 1, 3, and 4 possessed moderate estrogen partial agonistic activities, 1 and 2 possessed moderate antioxidant activities, and 2 and 3 possessed moderate alpha-glucosidase inhibitory activities. PMID- 26806330 TI - Development and Validation of a Near-Infrared Spectroscopy Method for the Prediction of Acrylamide Content in French-Fried Potato. AB - This study investigated the ability of near-infrared spectroscopy (NIRS) to predict acrylamide content in French-fried potato. Potato flour spiked with acrylamide (50-8000 MUg/kg) was used to determine if acrylamide could be accurately predicted in a potato matrix. French fries produced with various pretreatments and cook times (n = 84) and obtained from quick-service restaurants (n = 64) were used for model development and validation. Acrylamide was quantified using gas chromatography-mass spectrometry, and reflectance spectra (400-2500 nm) of each freeze-dried sample were captured on a Foss XDS Rapid Content Analyzer-NIR spectrometer. Partial least-squares (PLS) discriminant analysis and PLS regression modeling demonstrated that NIRS could accurately detect acrylamide content as low as 50 MUg/kg in the model potato matrix. Prediction errors of 135 MUg/kg (R(2) = 0.98) and 255 MUg/kg (R(2) = 0.93) were achieved with the best PLS models for acrylamide prediction in Russet Norkotah French-fried potato and multiple samples of unknown varieties, respectively. The findings indicate that NIRS can be used as a screening tool in potato breeding and potato processing research to reduce acrylamide in the food supply. PMID- 26806331 TI - Validation of the reliability of the Thai version of the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). AB - BACKGROUND: The Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) was developed to resolve problems associated with the original evaluation of cervical myelopathic patients. The aim of this study was to translate the JOACMEQ into Thai as per international recommendations, and to test its reliability and validity in the Thai context METHODS: The JOACMEQ was translated into Thai, using international guidelines. Cervical myelopathy patients (n = 70; 31 males) were asked to complete the Thai version JOACMEQ twice (4 weeks apart). Test-retest reliability was analyzed using the intra-class correlation coefficient (ICC). Internal consistencies were analyzed using Cronbach's alpha, while the construct validity was compared with the Thai version modified SF-36; using the Spearman's rank correlation coefficient. RESULTS: The Thai JOACMEQ produced good reliability (i.e., the ICC was >0.9 in 2 parameters and >0.8 in one). Overall the Cronbach's alpha for the 24 questions showed very high internal consistency (Cronbach's alpha > 0.8) and almost all Cronbach's alpha showed satisfactory internal consistency except for bladder function. The Spearman's rank correlation for all the JOACMEQ parameters had a positive correlation with all Thai SF 36 subscales, especially the quality of life parameter, which showed a strong correlation with all SF-36 subscales. CONCLUSION: The Thai version of the JOACMEQ had satisfactory internal consistency and test-retest reliability: it also had good construct validity. It can therefore be used as a reliable tool for assessing quality of life for cervical myelopathy patients in Thailand. PMID- 26806333 TI - Calcific myonecrosis arising in the bilateral deltoid muscles: A case report. PMID- 26806332 TI - Epidemiologic survey of locomotive syndrome in Japan. AB - BACKGROUND: The authors have developed a screening tool, the 25-Geriatric Locomotive Function Scale (GLFS-25), for the early detection of locomotive syndrome (LS). However, few studies have examined the prevalence of LS in the general population. This study estimated the prevalence of LS in Japan using the GLSF-25 and investigated age specific mean values for this scale. METHODS: A nationwide cross-sectional questionnaire survey was conducted to reveal standard values for the GLFS-25 and to estimate the total number of individuals with LS in Japan. Subjects were individuals selected from residents aged 40-79 years in Japan by a stratified, two-stage random sampling method in 2014. The survey period was from February to March 2014. A total of 9028 subjects were invited to participate. The GLFS-25 was used to estimate the prevalence of LS. We also investigated the degree of recognition of LS. RESULTS: Answers for the questionnaire were obtained from 5162 subjects (57.2%); 22.1% of responders had heard of LS. According to the GLSF-25, 614 subjects were regarded as having LS, representing a prevalence of 11.9%. When standardizing this value with the age distribution of the Japanese population, the total number of individuals with LS between the 40s and 70s in Japan was estimated to be approximately 7.5 million. Age specific standard values on the GLFS-25 were 4.4 in the 40s, 5.5 in the 50s, 7.1 in the 60s, and 12.7 in the 70s. The prevalence of LS increased with age and was particularly high in subjects aged 70-79. CONCLUSIONS: The degree of recognition of LS was 22%. This study demonstrated sex- and age specific standard values of the GLFS-25 and estimated the total number of individuals with LS in Japan based on a representative population. PMID- 26806334 TI - Spinal sagittal balance substantially influences locomotive syndrome and physical performance in community-living middle-aged and elderly women. AB - OBJECTIVES: Spinal sagittal imbalance has been well known risk factor of decreased quality of life in the field of adult spinal deformity. However, the impact of spinal sagittal balance on locomotive syndrome and physical performance in community-living elderly has not yet been clarified. The present study investigated the influence of spinal sagittal alignment on locomotive syndrome (LS) and physical performance in community-living middle-aged and elderly women. METHODS: A total of 125 women between the age of 40-88 years (mean 66.2 +/- 9.7 years) who completed the questionnaires, spinal mouse test, physical examination and physical performance tests in Yakumo study were enrolled in this study. Participants answered the 25-Question Geriatric Locomotive Function Scale (GLFS 25), the visual analog scale (VAS) for low back pain (LBP), knee pain. LS was defined as having a score of >16 points on the GLFS-25. Using spinal mouse, spinal inclination angle (SIA), thoracic kyphosis angle (TKA), lumbar lordosis angle (LLA), sacral slope angle (SSA), thoracic spinal range of motion (TSROM), lumbar spinal range of motion (LSROM) were measured. Timed-up-and-go test (TUG), one-leg standing time with eyes open (OLS), and maximum stride, back muscle strength were also measured. The relationship between spinal sagittal parameters and GLFS-25, VAS and physical performance tests were analyzed. RESULTS: 26 people were diagnosed as LS and 99 were diagnosed as non-LS. LBP and knee pain were greater, physical performance tests were poorer, SIA were greater, LLA were smaller in LS group compared to non-LS group even after adjustment by age. SIA significantly correlated with GLFS-25, TUG, OLS and maximum stride even after adjustment by age. The cutoff value of SIA for locomotive syndrome was 6 degrees . People with a SIA of 6 degrees or greater were grouped as "Inclined" and people with a SIA of less than 6 degrees were grouped as "Non-inclined". 21 people were "Inclined" and 104 were "Non-inclined". Odds ratio to fall in LS of Inclined group compared to Non-inclined group is 5.0. GLFS-25 were significantly higher, VAS for LBP were greater, TUG, OLS and maximum stride were poorer in Inclined group compared to Non-inclined group even after adjustment by age. CONCLUSIONS: The present study demonstrated that spinal sagittal balance influences the LS and physical performance in community-living middle-aged and elderly women. SIA is a useful spinal parameter to evaluate the risk of LS, and its cutoff value is 6 degrees . PMID- 26806336 TI - Quantitative Comparison of the Antimicrobial Efficiency of Leaching versus Nonleaching Polymer Materials. AB - New antimicrobial materials will be more and more in the focus for hygienic and clinical disease control. Antimicrobial materials have to be distinguished in leaching and nonleaching materials. For many applications of antimicrobial materials on implants the use of nonleaching materials is essential. Therefore, the antimicrobial efficiency of leaching and nonleaching polymers has been investigated quantitatively in vitro in direct comparison on a highly relevant implant of central venous catheters (CVCs) using a well-established called Certika test. This test is especially designed to test antimicrobial properties of leachable and nonleachable materials. This contribution demonstrates that newly developed nonleaching antimicrobial CVCs are equivalent to conventional leaching CVC systems in their antimicrobial performance against gram-positive and gram-negative bacteria, as well as Candida species. The use of new nonleaching antimicrobial polymers as shown here for CVCs represents a different mode of action with the aim to prevent infections also with antibiotic-resistant strains and reduced side effects. PMID- 26806337 TI - Carrier separation and charge transport characteristics of reduced graphene oxide supported visible-light active photocatalysts. AB - Extending the absorption to the visible region by tuning the optical band-gap of semiconductors and preventing charge carrier recombination are important parameters to achieve a higher efficiency in the field of photocatalysis. The inclusion of reduced graphene oxide (rGO) support in photocatalysts is one of the key strategies to address the above-mentioned issues. In this study, rGO supported AgI-mesoTiO2 photocatalysts were synthesized using a sonochemical approach. The physical effects of ultrasound not only improved the crystallinity of AgI-mesoTiO2 but also increased the surface area and loading of the AgI mesoTiO2 nanocomposite on rGO sheets. The low intense oxygen functionalities (C-O C and COOH groups) peak observed in the high resolution C1s spectrum of a hybrid AgI-mesoTiO2-rGO photocatalyst clearly confirmed the successful reduction of graphene oxide (GO) to rGO. The interfacial charge transfer between the rGO and the p-n junction of heterostructured photocatalysts has decreased the band-gap of the photocatalyst from 2.80 to 2.65 eV. Importantly, the integration of rGO into AgI-mesoTiO2 composites serves as a carrier separation centre and provides further insight into the electron transfer pathways of heterostructured nanocomposites. The individual effects of photo-generated electrons and holes over rGO on the photocatalytic degradation efficiency of rhodamine (RhB) and methyl orange (MO) using AgI-mesoTiO2-rGO photocatalysts were also studied. Our experimental results revealed that photo-generated superoxide (O2(-)) radicals are the main reactive species for the degradation of MO, whereas photo-generated holes (h(+)) are responsible for the degradation of RhB. As a result, 60% enhancement in MO degradation was observed in the presence of rGO in comparison to that of the pure AgI-mesoTiO2 photocatalyst. This is due to the good electron acceptor and the ultrafast electron transfer properties of rGO that can effectively reduce the molecular oxygen to produce a large amount of reactive O2( ) radicals. However, in the case of RhB degradation, h(+) is the main reactive species which showed a slightly increased photocatalytic activity (12%) in the presence of rGO support where the role of rGO is almost negligible. This study suggests the effective roles of rGO for the degradation of organics, i.e., the rate of photocatalytic degradation also depends on the nature of compound rather than rGO support. PMID- 26806339 TI - The mechanisms regulating cyclin-dependent kinase 5 in hippocampus during systemic inflammatory response: The effect on inflammatory gene expression. AB - Cyclin-dependent kinase 5 (Cdk5) is critical for nervous system's development and function, and its aberrant activation contributes to pathomechanism of Alzheimer's disease and other neurodegenerative disorders. It was recently suggested that Cdk5 may participate in regulation of inflammatory signalling. The aim of this study was to analyse the mechanisms involved in regulating Cdk5 activity in the brain during systemic inflammatory response (SIR) as well as the involvement of Cdk5 in controlling the expression of inflammatory genes. Genetic and biochemical alterations in hippocampus were analysed 3 and 12 h after intraperitoneal injection of lipopolysaccharide. We observed an increase in both Cdk5 gene expression and protein level. Moreover, phosphorylation of Cdk5 on Ser159 was significantly enhanced. Also transcription of Cdk5-regulatory protein (p35/Cdk5r1) was augmented, and the level of p25, calpain-dependent cleavage product of p35, was increased. All these results demonstrated rapid activation of Cdk5 in the brain during SIR. Hyperactivity of Cdk5 contributed to enhanced phosphorylation of tau and glycogen synthase kinase 3beta. Inhibition of Cdk5 with Roscovitine reduced activation of NF-kappaB and expression of inflammation related genes, demonstrating the critical role of Cdk5 in regulation of gene transcription during SIR. PMID- 26806341 TI - Computer vision for high content screening. AB - High Content Screening (HCS) technologies that combine automated fluorescence microscopy with high throughput biotechnology have become powerful systems for studying cell biology and drug screening. These systems can produce more than 100 000 images per day, making their success dependent on automated image analysis. In this review, we describe the steps involved in quantifying microscopy images and different approaches for each step. Typically, individual cells are segmented from the background using a segmentation algorithm. Each cell is then quantified by extracting numerical features, such as area and intensity measurements. As these feature representations are typically high dimensional (>500), modern machine learning algorithms are used to classify, cluster and visualize cells in HCS experiments. Machine learning algorithms that learn feature representations, in addition to the classification or clustering task, have recently advanced the state of the art on several benchmarking tasks in the computer vision community. These techniques have also recently been applied to HCS image analysis. PMID- 26806338 TI - Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma. AB - Ampullary carcinomas are highly malignant neoplasms that can have either intestinal or pancreatobiliary differentiation. To characterize somatic alterations in ampullary carcinomas, we performed whole-exome sequencing and DNA copy-number analysis on 60 ampullary carcinomas resected from clinically well characterized Japanese and American patients. We next selected 92 genes and performed targeted sequencing to validate significantly mutated genes in an additional 112 cancers. The prevalence of driver gene mutations in carcinomas with the intestinal phenotype is different from those with the pancreatobiliary phenotype. We identified a characteristic significantly mutated driver gene (ELF3) as well as previously known driver genes (TP53, KRAS, APC, and others). Functional studies demonstrated that ELF3 silencing in normal human epithelial cells enhances their motility and invasion. PMID- 26806342 TI - Albumin-Based Nanodevices as Drug Carriers. AB - Nanomedicine, the application of nanotechnology to medicine, is being increasingly used to improve and exploit the advantages of efficient drug delivery. Different nanodevices have been developed in recent years, among them protein-based nanoparticles which have gained considerable interest. Albumin is a versatile protein carrier with several characteristics that make it an ideal candidate for drug delivery, such as its availability, its biocompatibility, its biodegradability, and its lack of toxicity and immunogenicity. This review embodies an overview of different methods available for production of albumin based nanoparticles, with focus on high-energy emulsification methods. A comparison between production by using sonication, which involves acoustic cavitation, and the high pressure homogenization method, where occurs hydrodynamic cavitation, is presented. Taking into account important properties of nanoparticles required for intravenous administration, the use of poloxamers, tri-block copolymer surfactants is discussed as it improves blood circulation time and bioavailability of nanoparticles. Thus, nanoparticles can be engineered to provide adequate features to therapeutic applications, in which can be included surface functionalization with targeting agents. Different albumin-based formulations and their therapeutic applications are presented in this review, with emphasis on applications in cancer therapy, where albumin-based strategies are promising for targeted drug delivery in innovative clinical strategies. PMID- 26806343 TI - Liposome-Nanogel Structures for Future Pharmaceutical Applications: An Updated Review. AB - Nature uses combination of lipid bilayers and cross-linked macromolecular networks to achieve workability, multifunctionality, and dynamism in living cells of different types. Despite the concept of liposome-nanogel structures (lipobeads) is known for about 30 years, lipobead-based drug delivery systems are still largely experimental. The data available on nano- and giant lipobeads are reviewed to demonstrate technological achievability of lipobeads and to support the expectations that additional expenses on their production will be reimbursed by the potential advantages of their use. Indeed, lipobeads exhibit the properties attractive for the next generation of drug delivery systems: (i) retaining all the important benefits of polymeric and liposomal drug carriers, the hydrogel core brings mechanical stability and environmental responsiveness to the formulation in one construct, (ii) lipobeaddelivered combination therapy shows no toxicity on intravenously administered mice, accumulation of drug-loaded lipobeads both in the area surrounding tumor and within the tumor itself outside the vasculature, high therapeutic activity at the targeted site, and drastically increased survival, (iii) bipartite structure of lipobeads can provide a number of novel and unique options (e.g., consecutive multistep triggering and combined drug delivery systems). In addition, some ideas on the conceptually new drug delivery systems, new mechanisms of lipobead internalization into the cell and new schemes of drug release regulated by specific signaling are discussed. PMID- 26806344 TI - Statins and Type 2 Diabetes Mellitus: An Update After 1 Year. AB - In a review [1] published in this journal in 2014 we updated the role of statin treatment in patients with type 2 diabetes mellitus (T2DM). This is an important topic because the prevalence of T2DM is increasing and this disease is associated with a high risk of cardiovascular disease (CVD) as well as microvascular complications [1]. The relationship between T2DM and statins is further complicated since these drugs can cause new onset diabetes (NOD) although there is an overall benefit in terms of preventing vascular events [1, 2]. The cost implications of T2DM in terms of quality of life as well as providing healthcare are obvious. This is a brief update of our earlier review [1] based on recently published data. PMID- 26806345 TI - Insights Into Effects of Ellagic Acid on the Nervous System: A Mini Review. AB - Multiple lines of evidence suggest that disease-related neurodegeneration seems to be a multifactorial process that involves different cytotoxic pathways converging in cell death. Neuropathological evidence indicates that neuroinflammation, excitotoxicity, redox-active metals, increased reactive oxygen and nitrogen species, abnormalities in the activity of the ubiquitin-proteasome system, impairments in endogenous antioxidant defense mechanisms, mitochondrial dysfunction, as well as a reduction in the expression of trophic factors in neuronal tissues might play a role in the pathobiology of disease. In addition, increased expression of proapoptotic proteins, which leads to neuronal cell death, plays an important role in the onset and progression of neurodegeneration. With respect to the inefficacy of single-target drugs for the treatment of numerous neurodegenerative disorders, much attention has been paid to natural products with pluripharmacological properties as well as negligible adverse effects. Ellagic acid is known as an important natural phenolic antioxidant, that is widely found in different fruits and vegetables. Recent studies have shown that ellagic acid may invoke a spectrum of cell signaling pathways to attenuate or slow down the development of neurodegenerative disorders. Ellagic acid possesses potent neuroprotective effects through its free radical scavenging properties, iron chelation, activation of different cell signaling pathways, and mitigation of mitochondrial dysfunction. The aim of this review is to critically summarize and analyze the available literature regarding the neuroprotective effects of ellagic acid with emphasis on its molecular mechanisms of action. In addition, we also discuss the biosynthesis, sources, bioavailability, and metabolism, of ellagic acid to provide as accurately as possible the much needed information for assessment of the overall protective effects of this compound in the central nervous system. PMID- 26806346 TI - Opioid and Cannabinoid System in Food Intake. AB - Energy intake and expenditure are regulated by a complex network of neurochemical systems. The results of numerous studies have provided information about receptors involved, the sites of action within the brain and interactions between various systems, including opioid and cannabinoid, in regulation of energy balance. This review summarizes our present knowledge on the opioid and cannabinoid system appetite and satiety pathways. The involvement of the three main types of opioid receptors (MOR, DOR and KOR) and CB1 cannabinoid receptor, as well as the endogenous ligands of these receptors in food intake is documented. Finally, the use of opioid-cannabinoid system interactions as a new approach in the search for the next generation therapeutics controlling food intake disorders is discussed. PMID- 26806347 TI - Mechanistic Support for Combined MET and AR Blockade in Castration-Resistant Prostate Cancer. AB - A recent phase III trial of the MET kinase inhibitor cabozantinib in men with castration-resistant prostate cancer (CRPC) failed to meet its primary survival end point; however, most men with CRPC have intact androgen receptor (AR) signaling. As previous work supports negative regulation of MET by AR signaling, we hypothesized that intact AR signaling may have limited the efficacy of cabozantinib in some of these patients. To assess the role of AR signaling on MET inhibition, we first performed an in silico analysis of human CRPC tissue samples stratified by AR signaling status ((+) or (-)), which identified MET expression as markedly increased in AR(-) samples. In vitro, AR signaling inhibition in AR(+) CRPC models increased MET expression and resulted in susceptibility to ligand (HGF) activation. Likewise, MET inhibition was only effective in blocking cancer phenotypes in cells with MET overexpression. Using multiple AR(+) CRPC in vitro and in vivo models, we showed that combined cabozantinib and enzalutamide (AR antagonist) treatment was more efficacious than either inhibitor alone. These data provide a compelling rationale to combine AR and MET inhibition in CRPC and may explain the negative results of the phase III cabozantinib study in CRPC. Similarly, the expression of MET in AR(-) disease, whether due to AR inhibition or loss of AR signaling, suggests potential utility for MET inhibition in select patients with AR therapy resistance and in AR(-) prostate cancer. PMID- 26806348 TI - AMOTL1 Promotes Breast Cancer Progression and Is Antagonized by Merlin. AB - The Hippo signaling network is a key regulator of cell fate. In the recent years, it was shown that its implication in cancer goes well beyond the sole role of YAP transcriptional activity and its regulation by the canonical MST/LATS kinase cascade. Here we show that the motin family member AMOTL1 is an important effector of Hippo signaling in breast cancer. AMOTL1 connects Hippo signaling to tumor cell aggressiveness. We show that both canonical and noncanonical Hippo signaling modulates AMOTL1 levels. The tumor suppressor Merlin triggers AMOTL1 proteasomal degradation mediated by the NEDD family of ubiquitin ligases through direct interaction. In parallel, YAP stimulates AMOTL1 expression. The loss of Merlin expression and the induction of Yap activity that are frequently observed in breast cancers thus result in elevated AMOTL1 levels. AMOTL1 expression is sufficient to trigger tumor cell migration and stimulates proliferation by activating c-Src. In a large cohort of human breast tumors, we show that AMOTL1 protein levels are upregulated during cancer progression and that, importantly, the expression of AMOTL1 in lymph node metastasis appears predictive of the risk of relapse. Hence we uncover an important mechanism by which Hippo signaling promotes breast cancer progression by modulating the expression of AMOTL1. PMID- 26806349 TI - Isolation of Human CD138(+) Microparticles from the Plasma of Patients with Multiple Myeloma. AB - The confinement of multiple myeloma (MM) to the bone marrow microenvironment requires an invasive bone marrow biopsy to monitor the malignant compartment. The existing clinical tools used to determine treatment response and tumor relapse are limited in sensitivity mainly because they indirectly measure tumor burden inside the bone marrow and fail to capture the patchy, multisite tumor infiltrates associated with MM. Microparticles (MPs) are 0.1- to 1.0-MUm membrane vesicles, which contain the cellular content of their originating cell. MPs are functional mediators and convey prothrombotic, promalignant, proresistance, and proinflammatory messages, establishing intercellular cross talk and bypassing the need for direct cell-cell contact in many pathologies. In this study, we analyzed plasma cell-derived MPs (CD138(+)) from deidentified MM patients (n = 64) and normal subjects (n = 18) using flow cytometry. The morphology and size of the MPs were further analyzed using scanning electron microscopy. Our study shows the proof of a systemic signature of MPs in MM patients. We observed that the levels of MPs were significantly elevated in MM corresponding to the tumor burden. We provide the first evidence for the presence of MPs in the peripheral blood of MM patients with potential applications in personalized MM clinical monitoring. PMID- 26806350 TI - Synthesis, Characterization, and In Vitro and In Vivo Evaluations of 4-(N) Docosahexaenoyl 2', 2'-Difluorodeoxycytidine with Potent and Broad-Spectrum Antitumor Activity. AB - In this study, a new compound, 4-(N)-docosahexaenoyl 2', 2'-difluorodeoxycytidine (DHA-dFdC), was synthesized and characterized. Its antitumor activity was evaluated in cell culture and in mouse models of pancreatic cancer. DHA-dFdC is a poorly soluble, pale yellow waxy solid, with a molecular mass of 573.3Da and a melting point of about 96 degrees C. The activation energy for the degradation of DHA-dFdC in an aqueous Tween 80-based solution is 12.86kcal/mol, whereas its stability is significantly higher in the presence of vitamin E. NCI-60 DTP Human Tumor Cell Line Screening revealed that DHA-dFdC has potent and broad-spectrum antitumor activity, especially in leukemia, renal, and central nervous system cancer cell lines. In human and murine pancreatic cancer cell lines, the IC50 value of DHA-dFdC was up to 10(5)-fold lower than that of dFdC. The elimination of DHA-dFdC in mouse plasma appeared to follow a biexponential model, with a terminal phase t1/2 of about 58minutes. DHA-dFdC significantly extended the survival of genetically engineered mice that spontaneously develop pancreatic ductal adenocarcinoma. In nude mice with subcutaneously implanted human Panc-1 pancreatic tumors, the antitumor activity of DHA-dFdC was significantly stronger than the molar equivalent of dFdC alone, DHA alone, or the physical mixture of them (1:1, molar ratio). DHA-dFdC also significantly inhibited the growth of Panc 1 tumors orthotopically implanted in the pancreas of nude mice, whereas the molar equivalent dose of dFdC alone did not show any significant activity. DHA-dFdC is a promising compound for the potential treatment of cancers in organs such as the pancreas. PMID- 26806351 TI - Targeting of CCL2-CCR2-Glycosaminoglycan Axis Using a CCL2 Decoy Protein Attenuates Metastasis through Inhibition of Tumor Cell Seeding. AB - The CCL2-CCR2 chemokine axis has an important role in cancer progression where it contributes to metastatic dissemination of several cancer types (e.g., colon, breast, prostate). Tumor cell-derived CCL2 was shown to promote the recruitment of CCR2(+)/Ly6C(hi) monocytes and to induce vascular permeability of CCR2(+) endothelial cells in the lungs. Here we describe a novel decoy protein consisting of a CCL2 mutant protein fused to human serum albumin (dnCCL2-HSA chimera) with enhanced binding affinity to glycosaminoglycans that was tested in vivo. The monocyte-mediated tumor cell transendothelial migration was strongly reduced upon unfused dnCCL2 mutant treatment in vitro. dnCCL2-HSA chimera had an extended serum half-life and thus a prolonged exposure in vivo compared with the dnCCL2 mutant. dnCCL2-HSA chimera bound to the lung vasculature but caused minimal alterations in the leukocyte recruitment to the lungs. However, dnCCL2-HSA chimera treatment strongly reduced both lung vascular permeability and tumor cell seeding. Metastasis of MC-38GFP, 3LL, and LLC1 cells was significantly attenuated upon dnCCL2-HSA chimera treatment. Tumor cell seeding to the lungs resulted in enhanced expression of a proteoglycan syndecan-4 by endothelial cells that correlated with accumulation of the dnCCL2-HSA chimera in the vicinity of tumor cells. These findings demonstrate that the CCL2-based decoy protein effectively binds to the activated endothelium in lungs and blocks tumor cell extravasation through inhibition of vascular permeability. PMID- 26806353 TI - Blind aspiration biopsy versus a guided hysteroscopic technique for investigation of the endometrium in infertile women. AB - Embryo implantation failure and recurrent abortion are common indications for endometrial evaluation to determine the implantation window and diagnose endometrial anomalies. There are few research studies comparing the efficacy of different techniques used for endometrial sampling in infertile females during the luteal phase. Likewise, morphometric studies of the endometrium through aspiration biopsy are scant. A cross-sectional study of 30 infertile and 10 fertile females was carried out. The study participants underwent hysteroscopic and aspiration biopsies (pipelle) at the midluteal phase. Computer-assisted morphometric and pathological anatomy analyses were conducted independently by two pathologists blinded to the study. The two endometrial sampling biopsy techniques were compared through morphometric and pathological anatomy analyses using three parameters: a) the amount of material collected for the endometrial studies; b) the scope and origin of sampled materials; and c) the quality of the sample. Both biopsy techniques produced sufficient material for analysis. The directed biopsies yielded higher quality samples from targeted segments of the uterine cavity because samples were homogeneous and had no architectural distortion (p<0.05). Blood was present only in the samples obtained through a Pipelle. Endometritis was detected in 10% of the infertile women. Our findings suggest that hysteroscopic biopsies are superior to blinded aspiration biopsies. PMID- 26806352 TI - A Novel Mouse Model of Diffuse Intrinsic Pontine Glioma Initiated in Pax3 Expressing Cells. AB - Diffuse intrinsic pontine glioma (DIPG) is a rare and incurable brain tumor that arises predominately in children and involves the pons, a structure that along with the midbrain and medulla makes up the brainstem. We have previously developed genetically engineered mouse models of brainstem glioma using the RCAS/Tv-a system by targeting PDGF-B overexpression, p53 loss, and H3.3K27M mutation to Nestin-expressing brainstem progenitor cells of the neonatal mouse. Here we describe a novel mouse model targeting these same genetic alterations to Pax3-expressing cells, which in the neonatal mouse pons consist of a Pax3+/Nestin+/Sox2+ population lining the fourth ventricle and a Pax3+/NeuN+ parenchymal population. Injection of RCAS-PDGF-B into the brainstem of Pax3-Tv-a mice at postnatal day 3 results in 40% of mice developing asymptomatic low-grade glioma. A mixture of low- and high-grade glioma results from injection of Pax3-Tv a;p53(fl/fl) mice with RCAS-PDGF-B and RCAS-Cre, with or without RCAS-H3.3K27M. These tumors are Ki67+, Nestin+, Olig2+, and largely GFAP- and can arise anywhere within the brainstem, including the classic DIPG location of the ventral pons. Expression of the H3.3K27M mutation reduces overall H3K27me3 as compared with tumors without the mutation, similar to what has been previously shown in human and mouse tumors. Thus, we have generated a novel genetically engineered mouse model of DIPG, which faithfully recapitulates the human disease and represents a novel platform with which to study the biology and treatment of this deadly disease. PMID- 26806354 TI - Dmy initiates masculinity by altering Gsdf/Sox9a2/Rspo1 expression in medaka (Oryzias latipes). AB - Despite identification of several sex-determining genes in non-mammalian vertebrates, their detailed molecular cascades of sex determination/differentiation are not known. Here, we used a novel RNAi to characterise the molecular mechanism of Dmy (the sex-determining gene of medaka) mediated masculinity in XY fish. Dmy knockdown (Dmy-KD) suppressed male pathway (Gsdf, Sox9a2, etc.) and favoured female cascade (Rspo1, etc.) in embryonic XY gonads, resulting in a fertile male-to-female sex-reversal. Gsdf, Sox9a2, and Rspo1 directly interacted with Dmy, and co-injection of Gsdf and Sox9a2 re established masculinity in XY-Dmy-KD transgenics, insinuating that Dmy initiates masculinity by stimulating and suppressing Gsdf/Sox9a2 and Rspo1 expression, respectively. Gonadal expression of Wt1a starts prior to Dmy and didn't change upon Dmy-KD. Furthermore, Wt1a stimulated the promoter activity of Dmy, suggesting Wt1a as a regulator of Dmy. These findings provide new insights into the role of vertebrate sex-determining genes associated with the molecular interplay between the male and female pathways. PMID- 26806355 TI - A new basal bird from China with implications for morphological diversity in early birds. AB - The Chinese Lower Cretaceous Jehol Group is the second oldest fossil bird-bearing deposit, only surpassed by Archaeopteryx from the German Upper Jurassic Solnhofen Limestones. Here we report a new bird, Chongmingia zhengi gen. et sp. nov., from the Jehol Biota. Phylogenetic analyses indicate that Chongmingia zhengi is basal to the dominant Mesozoic avian clades Enantiornithes and Ornithuromorpha, and represents a new basal avialan lineage. This new discovery adds to our knowledge regarding the phylogenetic differentiation and morphological diversity in early avian evolution. The furcula of Chongmingia is rigid (reducing its efficiency), consequently requiring more power for flight. However, the elongated forelimb and the large deltopectoral crest on the humerus might indicate that the power was available. The unique combination of features present in this species demonstrates that numerous evolutionary experimentations took place in the early evolution of powered flight. The occurrence of gastroliths further confirms that herbivory was common among basal birds. The Jehol birds faced competition with pterosaurs, and occupied sympatric habitats with non-avian theropods, some of which consumed birds. Thus, avialan herbivory may have reduced ecological competition from carnivorous close relatives and other volant vertebrates early in their evolutionary history. PMID- 26806356 TI - Scale-up of industrial biodiesel production to 40 m(3) using a liquid lipase formulation. AB - In this work, we demonstrate the scale-up from an 80 L fed-batch scale to 40 m(3) along with the design of a 4 m(3) continuous process for enzymatic biodiesel production catalyzed by NS-40116 (a liquid formulation of a modified Thermomyces lanuginosus lipase). Based on the analysis of actual pilot plant data for the transesterification of used cooking oil and brown grease, we propose a method applying first order integral analysis to fed-batch data based on either the bound glycerol or free fatty acid content in the oil. This method greatly simplifies the modeling process and gives an indication of the effect of mixing at the various scales (80 L to 40 m(3) ) along with the prediction of the residence time needed to reach a desired conversion in a CSTR. Suitable process metrics reflecting commercial performance such as the reaction time, enzyme efficiency, and reactor productivity were evaluated for both the fed-batch and CSTR cases. Given similar operating conditions, the CSTR operation on average, has a reaction time which is 1.3 times greater than the fed-batch operation. We also showed how the process metrics can be used to quickly estimate the selling price of the enzyme. Assuming a biodiesel selling price of 0.6 USD/kg and a one time use of the enzyme (0.1% (w/woil ) enzyme dosage); the enzyme can then be sold for 30 USD/kg which ensures that that the enzyme cost is not more than 5% of the biodiesel revenue. Biotechnol. Bioeng. 2016;113: 1719-1728. (c) 2016 Wiley Periodicals, Inc. PMID- 26806358 TI - Proteomic response of methicillin-resistant S. aureus to a synergistic antibacterial drug combination: a novel erythromycin derivative and oxacillin. AB - The use of antibacterial drug combinations with synergistic effects is increasingly seen as a critical strategy to combat multi-drug resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). In this work, the proteome responses in MRSA under the stress of a sub-inhibitory dose of a synergistic drug combination of a novel erythromycin derivative, SIPI-8294, and oxacillin, were studied by label-free quantitative proteomics. Several control treatment groups were designed to isolate proteome responses potentially related to the synergy: (1) the non-synergistic drug combination of erythromycin and oxacillin, (2) SIPI-8294 only, (3) oxacillin only and (4) erythromycin only. Results showed that 200 proteins were differentially expressed in SIPI 8294/oxacillin-treated cells. Among these proteins, the level of penicillin binding protein 2a, the protein mainly responsible for oxacillin resistance in MRSA, was four times lower in the SIPI-8294/oxacillin group than in the erythromycin/oxacillin group, suggesting that SIPI-8294 may interfere with this known oxacillin resistance mechanism. Moreover, hierarchical clustering analysis of differentially expressed proteins under different treatments revealed that SIPI-8294/oxacillin elicits very different responses than the individual drugs or the non-synergistic erythromycin/oxacillin combination. Bioinformatic analysis indicated that the synergistic effect can be further traced to a disruption in oxidation-reduction homeostasis and cell wall biosynthesis. PMID- 26806360 TI - Quantitation of intrathecal immunoglobulin synthesis - a new empirical formula. AB - BACKGROUND AND PURPOSE: Intrathecal immunoglobulin (Ig) synthesis occurs in various chronic inflammatory neurological diseases. Different formulae have been developed for quantitative determination of Ig synthesis within the cerebrospinal fluid (CSF) compartment. The hyperbolic formula of Reiber is frequently used which, however, returns a considerable number of false positive results in empirical observations. METHODS: A computerized database of more than 19 000 paired CSF and serum samples was screened for patients presumed negative for local Ig synthesis and a new formula characterizing this collective was calculated. The validity of this formula was confirmed by several validation steps. RESULTS: A cohort of 1173 patients with normal CSF findings was used for quantile regression. The 97.5th quantile of the formula Qlim(IgX)=a*Qalbb was considered as the cut-off curve for intrathecal Ig synthesis using different constants a and b for IgG, IgA and IgM. Compared to the Reiber formula, a lower level of false positive results was produced especially for IgM and IgA which was confirmed in a separate clinically well defined validation cohort. In 77 patients with discrepant findings between Reiber and our formula no specific diagnoses were found confirming the low diagnostic value of borderline Ig synthesis. CONCLUSIONS: A new approximation formula was developed for determination of intrathecal Ig synthesis which produces fewer false positive results without reducing diagnostic sensitivity. PMID- 26806361 TI - Australia and the Australian Cerebral Palsy Register for the birth cohort 1993 to 2006. AB - This is a brief background paper for a supplementary issue of Developmental Medicine & Child Neurology by the Australian Cerebral Palsy Register Group. It provides context for the reader of the supplement including a description of the establishment and development of state and territory cerebral palsy registers in Australia. PMID- 26806362 TI - Breast Cancer Stem Cell Potent Copper(II)-Non-Steroidal Anti-Inflammatory Drug Complexes. AB - The breast cancer stem cell (CSC) potency of a series of copper(II) phenanthroline complexes containing the nonsteroidal anti-inflammatory drug (NSAID), indomethacin, is reported. The most effective copper(II) complex in this series, 4, selectivity kills breast CSC-enriched HMLER-shEcad cells over breast CSC-depleted HMLER cells. Furthermore, 4 reduces the formation, size, and viability of mammospheres, to a greater extent than salinomycin, a potassium ionophore known to selectively inhibit CSCs. Mechanistic studies revealed that the CSC-specificity observed for 4 arises from its ability to generate intracellular reactive oxygen species (ROS) and inhibit cyclooxygenase-2 (COX-2), an enzyme that is overexpressed in breast CSCs. The former induces DNA damage, activates JNK and p38 pathways, and leads to apoptosis. PMID- 26806363 TI - Risk of Death in Bullous Pemphigoid: A Retrospective Database Study in Finland. AB - Bullous pemphigoid (BP) is an autoimmune skin disease of elderly people, which is associated with increased mortality. The aim of this study was to investigate the standardized mortality ratio (SMR) for BP in Finland, and concomitant comorbidities and medications. This was a retrospective database study of all cases of BP diagnosed at the Department of Dermatology, Oulu University Hospital, Finland, between 1985 and 2012. A total of 198 immunologically confirmed cases of BP were found. One-year mortality was 16.7%, and SMR 7.56 (95% confidence interval (CI) 4.98-10.14). The most common comorbidities were cardiovascular diseases (76.3%) and neurodegenerative diseases (40.9%). Malignancies (8.6%) were associated with increased mortality (hazard ratio = 2.4, 95% CI 1.1-5.5, p = 0.047). A novel finding was that polypharmacy was very common in patients with BP, and the higher the number of drugs, the greater the mortality. In conclusion, the mortality for BP in Finland is 7.6-fold that of a reference population, and malignancies and polypharmacy are associated with increased mortality. PMID- 26806364 TI - Altered Cholesterol Metabolism and Hypocholesterolemia in Patients with Single Ventricle following Fontan Palliation. AB - OBJECTIVE: To assess whether an abnormality in cholesterol absorption or synthesis may be associated with hypocholesterolemia in patients with single ventricle anatomy following Fontan palliation. STUDY DESIGN: This is a cross sectional study of 21 patients with hypocholesterolemia following Fontan procedure and age/sex-matched healthy controls, with median age of 13.4 (IQR 10.6 16.1) years. Laboratory values of several biomarkers, including phytosterols and 5-alpha-cholestanol (for cholesterol absorption) and lathosterol (for cholesterol biosynthesis), as well as cholesterol levels, inflammatory markers, and indices of liver function were compared between patients following Fontan procedure and controls. RESULTS: The Fontan cohort had significantly lower total cholesterol (mean 117 +/- SD 13.9, vs 128 +/- 19.2 mg/dL, P = .03) and free cholesterol (35.5 +/- 4.5 vs 39.2 +/- 5.4 mg/dL, P = .02) compared with control patients. There was an increase in normalized 5-alpha-cholestanol (1.51 +/- 0.6 vs 1.14 +/- 0.37 MUg/mL, P = .02), and a significantly lower lathosterol/5-alpha-cholestanol ratio (0.70 +/- 0.38 vs 1.11 +/- 0.76, P = .04). There was a strong correlation (r = 0.78, P < .0001) between lathosterol and cholesterol levels in the Fontan cohort, not seen in controls (r = 0.47, P = .04). The Fontan cohort also had significantly higher C-reactive protein, transaminases, total bilirubin, and gamma-glutamyl transferase levels. CONCLUSIONS: Patients with hypocholesterolemia following Fontan procedure have evidence of increased cholesterol absorption and decreased cholesterol synthesis. As cholesterol absorption efficiency is a regulated process, this finding suggests an upregulation of cholesterol absorption as a result of decreased cholesterol production. In the setting of elevated liver indices and possible inflammation, this finding supports a growing body of data suggesting development of liver disease in patients receiving Fontan. PMID- 26806365 TI - Computer-based cognitive interventions for people living with dementia: a systematic literature review and meta-analysis. AB - OBJECTIVES: To estimate the efficacy of computer-based cognitive interventions for improving cognition in people with dementia (PWD). METHOD: Online literature databases were searched for relevant studies. Interventions were categorised as follows: cognitive recreation, cognitive rehabilitation, cognitive stimulation or cognitive training. A systematic review, quality assessment and meta-analyses were conducted. RESULTS: Twelve studies were identified. Their methodological quality was acceptable according to Downs & Black criteria, the weakest methodological area being the external validity. The meta-analyses indicated cognitive interventions lead to beneficial effects on cognition in PWD (SMD 0.69; 95% CI = 1.02-0.37; P < 0.0001; I(2) = 29%), [corrected] depression (SMD 0.47; 95% CI = 0.16-0.78; P = 0.003; I(2) = 0%) and anxiety (SMD 0.55; 95% CI = 0.07 1.04; P < 0.03; I(2) = 42%). [corrected]. They benefited significantly more from the computer-based cognitive interventions than from the non-computer-based interventions in cognition (SMD 0.48; 95% CI = 0.09-0.87; [corrected] P = 0.02; I(2) = 2%). CONCLUSION: Computer-based cognitive interventions have moderate effects in cognition and [corrected] anxiety and small effects in depression in PWD. No significant effects were found on activities of daily living. They led to superior results compared to non-computer-based interventions in cognition. Further research is needed on cognitive recreation and cognitive stimulation. There is also a need for longer term [corrected] follow-up to examine the potential retention of treatment effects, and for the design of specific outcome measures. PMID- 26806366 TI - Corrigendum. PMID- 26806369 TI - Pregnancy outcome after tocilizumab therapy in early pregnancy-a case series from the German Embryotox Pharmacovigilance Center. AB - Tocilizumab (TCZ) is not recommended for use during pregnancy due to limited data, but pregnancies nevertheless occur and pregnant women need to be counseled about potential fetal risks. Participants of this study were recruited from the pool of callers who spontaneously contact the pharmacovigilance center "Embryotox" Berlin for risk assessment during pregnancy. Of 22 identified cases with TCZ exposure during pregnancy, 16 prospectively enrolled cases with maternal and two cases with paternal TCZ therapy could be completed. The outcomes of the 16 maternal cases were: four spontaneous abortions (SAB), one induced abortion for personal reasons and 11 live-born infants. Congenital malformations were not recorded, but one SAB at week 15+3 days was complicated by hydrops fetalis of unknown origin. An incidental continuation of TCZ into early pregnancy does not justify an elective termination. However, a detailed prenatal ultrasound should be offered. PMID- 26806370 TI - Multifaceted roles of neuroinflammation: the need to consider both sides of the coin. PMID- 26806372 TI - Enantiopure titanocene complexes--direct evidence for paraptosis in cancer cells. AB - Tolerated by normal tissues, anti-cancer therapies based on titanium compounds are limited by low efficacy/selectivity and lack of understanding of their mode(s) of action. In vitro antitumour activity and mode of cell death incurred by enantiopure TiCl2{eta-C5H4CHEt(2-MeOPh)}2 (abbreviated Cp(R)2TiCl2) has been investigated. The in vitro anti-tumour activity of Cp(R)2TiCl2 is selective for cancer cells; in clonogenic assays, (S,S)-Cp(R)2TiCl2 was twice as effective at inhibiting colony formation than other stereoisomers after 24 h exposure. HPLC, MS and NMR techniques determined hydrolysis of Cp(R)2TiCl2; data strongly correlate with soluble [Cp(R)2Ti(OH)(OH2)](+) being the biological trigger. Treatment of cells with Cp(R)2TiCl2 provoked extensive cytoplasmic vacuolization, endoplasmic reticulum (ER) swelling and activation of MAPKinase signal transduction, consistent with ligand-induced paraptosis, type III cell death, which is morphologically distinct from, and independent of apoptosis. Indeed, distinct from cisplatin, Cp(R)2TiCl2 failed to perturb cell cycle dynamics, induce gammaH2AX foci or evoke apoptosis in MDA-MB-468 and HCT-116 cells. PMID- 26806371 TI - Differential detection of impact site versus rotational site injury by magnetic resonance imaging and microglial morphology in an unrestrained mild closed head injury model. AB - Seventy-five percent of all traumatic brain injuries are mild and do not cause readily visible abnormalities on routine medical imaging making it difficult to predict which individuals will develop unwanted clinical sequelae. Microglia are brain-resident macrophages and early responders to brain insults. Their activation is associated with changes in morphology or expression of phenotypic markers including P2Y12 and major histocompatibility complex class II. Using a murine model of unrestrained mild closed head injury (mCHI), we used microglia as reporters of acute brain injury at sites of impact versus sites experiencing rotational stress 24 h post-mCHI. Consistent with mild injury, a modest 20% reduction in P2Y12 expression was detected by quantitative real-time PCR (qPCR) analysis but only in the impacted region of the cortex. Furthermore, neither an influx of blood-derived immune cells nor changes in microglial expression of CD45, TREM1, TREM2, major histocompatibility complex class II or CD40 were detected. Using magnetic resonance imaging (MRI), small reductions in T2 weighted values were observed but only near the area of impact and without overt tissue damage (blood deposition, edema). Microglial morphology was quantified without cryosectioning artifacts using ScaleA(2) clarified brains from CX3CR1-green fluorescence protein (GFP) mice. The cortex rostral to the mCHI impact site receives greater rotational stress but neither MRI nor molecular markers of microglial activation showed significant changes from shams in this region. However, microglia in this rostral region did display signs of morphologic activation equivalent to that observed in severe CHI. Thus, mCHI-triggered rotational stress is sufficient to cause injuries undetectable by routine MRI that could result in altered microglial surveillance of brain homeostasis. Acute changes in microglial morphology reveal brain responses to unrestrained mild traumatic brain injury In areas subjected to rotational stress distant from impact site In the absence of detectable changes in standard molecular indicators of brain damage, inflammation or microglial activation. That might result in decreased surveillance of brain function and increased susceptibility to subsequent brain insults. PMID- 26806373 TI - Assessment of neonatal platelet adhesion, activation, and aggregation. AB - BACKGROUND: Acquired and inherited bleeding disorders may present in the neonatal period with devastating lifelong effects. Diagnosing bleeding disorders in the neonatal population could aid in preventing and treating the associated complications. However, currently available platelet function testing is limited in neonates, owing to difficulties in obtaining an adequate blood volume, a lack of normal reference ranges, and an incomplete understanding of the neonatal platelet functional phenotype. OBJECTIVE: To develop small-volume, whole blood platelet function assays in order to quantify and compare neonatal and adult platelet function. METHODS AND RESULTS: Peripheral blood was obtained from healthy, full-term neonates at 24 h of life. Platelet activation, secretion and aggregation were measured via flow cytometry. Platelet adhesion and aggregation were assessed under static and flow conditions. As compared with adult platelets, peripheral neonatal platelet P-selectin expression and integrin glycoprotein IIbIIIa activation were significantly reduced in response to the G-protein coupled receptor (GPCR) agonists thrombin receptor activator peptide-6 (TRAP-6), ADP, and U46619, and the immunoreceptor tyrosine-based activation motif (ITAM) signaling pathway agonists collagen-related peptide (CRP) and rhodocytin. Neonatal platelet aggregation was markedly reduced in response to TRAP-6, ADP, U46619, CRP and rhodocytin as compared with adult platelets. The extents of neonatal and adult platelet adhesion and aggregate formation under static and shear conditions on collagen and von Willebrand factor were similar. CONCLUSIONS: As compared with adult platelets, we found that neonatal platelet activation and secretion were blunted in response to GPCR or ITAM agonists, whereas the extent of neonatal platelet adhesion and aggregate formation was similar to that of adult platelets. PMID- 26806376 TI - Echinocandin resistance and population structure of invasive Candida glabrata isolates from two university hospitals in Germany and Austria. AB - Echinocandin resistance in Candida glabrata is emerging and is associated with the presence of FKS mutations. In this study, we analysed the antifungal susceptibility, presence of FKS mutations and clonality of C. glabrata blood culture isolates from two hospitals in Germany and Austria. Susceptibility testing of 64 C. glabrata bloodstream isolates from two university hospitals was performed with broth microdilution method according to EUCAST. In addition, all isolates were screened for FKS mutations. Molecular fingerprinting was performed by microsatellite PCR with three separate primer pairs and semiautomated repetitive sequenced-based PCR (rep-PCR). One C. glabrata isolate from Germany (1.5%) was echinocandin resistant, with a corresponding mutation in FKS2 gene hot spot 1. The discriminatory power of microsatellite PCR was higher than that of rep-PCR (Simpson Index of 0.94 vs. 0.88); microsatellite PCR created 31 separate genotypes, whereas rep-PCR created 17. Predominant genotypes or clusters of isolates from Germany and Austria were present, with no epidemiological evidence of nosocomial transmissions. Although we found a low incidence of echinocandin resistance in C. glabrata in our settings, further surveillance projects in central Europe are warranted for monitoring future epidemiological trends. The genetic population structure of C. glabrata demonstrates overrepresented geographical clusters. PMID- 26806374 TI - Inflammatory Airway Disease of Horses--Revised Consensus Statement. AB - The purpose of this manuscript is to revise and update the previous consensus statement on inflammatory airway disease (IAD) in horses. Since 2007, a large number of scientific articles have been published on the topic and these new findings have led to a significant evolution of our understanding of IAD. PMID- 26806377 TI - Diagnostic value of thyroid transcription factor-1 for pleural or other serous metastases of pulmonary adenocarcinoma: a meta-analysis. AB - The role of thyroid transcription factor 1 (TTF-1) in the diagnosis of metastatic pulmonary adenocarcinomas in pleural, pericardial, and peritoneal effusions has not been defined. This study aimed to assess the overall diagnostic accuracy of TTF-1 for metastatic pulmonary adenocarcinomas in pleural or other effusions. Literature search was conducted in PubMed, EMBASE, and other databases to find eligible publications. Quality was assessed according to standardized QUADAS-2 criteria. Sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR) were pooled. Summary receiver operating characteristic (SROC) curves were used to assess overall performance of the TTF-1 assay. A systematic search revealed 20 studies comprising a total of 1,213 subjects in this meta-analysis. The summary estimates were listed as follows: sensitivity, 0.74 (95% CI: 0.69-0.79); specificity, 0.99 (95% CI: 0.97-1.00); PLR, 78.16 (95% CI: 27.15-225.05); NLR, 0.26 (95% CI: 0.22-0.32); and diagnostic odds ratio, 297.75 (95% CI: 104.16-851.19). Estimated positive and negative post probability values for metastatic pulmonary adenocarcinomas prevalence of 20% were 95% and 6%, respectively. The area under the SROC curve was 0.96. TTF-1 shows significant potential as a diagnostic marker to differentiate metastatic pulmonary from non-pulmonary adenocarcinomas in pleural or other effusions. These results justify larger, more rigorous studies to confirm such a diagnostic role. PMID- 26806378 TI - Lost opportunities to identify and treat HIV-positive patients: results from a baseline assessment of provider-initiated HIV testing and counselling (PITC) in Malawi. AB - OBJECTIVE: To assess implementation of provider-initiated testing and counselling (PITC) for HIV in Malawi. METHODS: A review of PITC practices within 118 departments in 12 Ministry of Health (MoH) facilities across Malawi was conducted. Information on PITC practices was collected via a health facility survey. Data describing patient visits and HIV tests were abstracted from routinely collected programme data. RESULTS: Reported PITC practices were highly variable. Most providers practiced symptom-based PITC. Antenatal clinics and maternity wards reported widespread use of routine opt-out PITC. In 2014, there was approximately 1 HIV test for every 15 clinic visits. HIV status was ascertained in 94.3% (5293/5615) of patients at tuberculosis clinics, 92.6% (30,675/33,142) of patients at antenatal clinics and 49.4% (6871/13,914) of patients at sexually transmitted infection clinics. Reported challenges to delivering PITC included test kit shortages (71/71 providers), insufficient physical space (58/71) and inadequate number of HIV counsellors (32/71) while providers from inpatient units cited the inability to test on weekends. CONCLUSIONS: Various models of PITC currently exist at MoH facilities in Malawi. Only antenatal and maternity clinics demonstrated high rates of routine opt-out PITC. The low ratio of facility visits to HIV tests suggests missed opportunities for HIV testing. However, the high proportion of patients at TB and antenatal clinics with known HIV status suggests that routine PITC is feasible. These results underscore the need to develop clear, standardised PITC policy and protocols, and to address obstacles of limited health commodities, infrastructure and human resources. PMID- 26806381 TI - A fragment merging approach towards the development of small molecule inhibitors of Mycobacterium tuberculosis EthR for use as ethionamide boosters. AB - With the ever-increasing instances of resistance to frontline TB drugs there is the need to develop novel strategies to fight the worldwide TB epidemic. Boosting the effect of the existing second-line antibiotic ethionamide by inhibiting the mycobacterial transcriptional repressor protein EthR is an attractive therapeutic strategy. Herein we report the use of a fragment based drug discovery approach for the structure-guided systematic merging of two fragment molecules, each binding twice to the hydrophobic cavity of EthR from M. tuberculosis. These together fill the entire binding pocket of EthR. We elaborated these fragment hits and developed small molecule inhibitors which have a 100-fold improvement of potency in vitro over the initial fragments. PMID- 26806384 TI - Candida albicans biofilms: development, regulation, and molecular mechanisms. AB - A major virulence attribute of Candida albicans is its ability to form biofilms, densely packed communities of cells adhered to a surface. These biofilms are intrinsically resistant to conventional antifungal therapeutics, the host immune system, and other environmental factors, making biofilm-associated infections a significant clinical challenge. Here, we review current knowledge on the development, regulation, and molecular mechanisms of C. albicans biofilms. PMID- 26806385 TI - Blood metabolite markers of preclinical Alzheimer's disease in two longitudinally followed cohorts of older individuals. AB - INTRODUCTION: Recently, quantitative metabolomics identified a panel of 10 plasma lipids that were highly predictive of conversion to Alzheimer's disease (AD) in cognitively normal older individuals (n = 28, area under the curve [AUC] = 0.92, sensitivity/specificity of 90%/90%). METHODS: Quantitative targeted metabolomics in serum using an identical method as in the index study. RESULTS: We failed to replicate these findings in a substantially larger study from two independent cohorts-the Baltimore Longitudinal Study of Aging ([BLSA], n = 93, AUC = 0.642, sensitivity/specificity of 51.6%/65.7%) and the Age, Gene/Environment Susceptibility-Reykjavik Study ([AGES-RS], n = 100, AUC = 0.395, sensitivity/specificity of 47.0%/36.0%). In analyses applying machine learning methods to all 187 metabolite concentrations assayed, we find a modest signal in the BLSA with distinct metabolites associated with the preclinical and symptomatic stages of AD, whereas the same methods gave poor classification accuracies in the AGES-RS samples. DISCUSSION: We believe that ours is the largest blood biomarker study of preclinical AD to date. These findings underscore the importance of large-scale independent validation of index findings from biomarker studies with relatively small sample sizes. PMID- 26806386 TI - Beta-amyloid and cognitive decline in late middle age: Findings from the Wisconsin Registry for Alzheimer's Prevention study. AB - INTRODUCTION: The present study investigated the relationship between beta amyloid (Abeta) and cognition in a late middle-aged cohort at risk for Alzheimer's disease (AD). METHODS: One eighty-four participants (mean age = 60; 72% parental history of AD) completed a [C-11]Pittsburgh compound B positron emission tomography scan and serial cognitive evaluations. A global measure of Abeta burden was calculated, and composite scores assessing learning, delayed memory, and executive functioning were computed. RESULTS: Higher Abeta was associated with classification of psychometric mild cognitive impairment (MCI) at follow-up (P < .01). Linear mixed effects regression results indicated higher Abeta was associated with greater rates of decline in delayed memory (P < .01) and executive functioning (P < .05). Apolipoprotein E (APOE) epsilon4 status moderated the relationship between Abeta and cognitive trajectories (P values <.01). DISCUSSION: In individuals at risk for AD, greater Abeta in late middle age is associated with increased likelihood of MCI at follow-up and steeper rates of cognitive decline. PMID- 26806387 TI - Validating Alzheimer's disease micro RNAs using next-generation sequencing. AB - INTRODUCTION: Molecular biomarkers for Alzheimer's disease (AD) can support detection and improved care for patients, but novel candidates require verification. We previously reported a 12-micro RNA (miRNA) blood-based signature using next-generation sequencing (NGS) of 54 AD cases and 22 controls. METHODS: We performed validation of 49 AD cases and 55 controls using NGS and also included 20 mild cognitive impairment and 90 multiple sclerosis samples to identify nonspecific markers. Thus, 103 AD cases, 77 unaffected controls, and 110 diseased controls were sequenced. Although the initial cohort came predominantly from the United States, the validation samples were collected in Germany. RESULTS: Five hundred eighty miRNAs were detected in the blood. In the initial cohort, we observed 203, in the validation cohort, 146 dysregulated miRNAs at a significance level of 0.05. With 68 miRNAs, the overlap was significant (P = .0003). Likewise, the area under the receiver operator characteristic curve values of the miRNAs correlated (correlation of 0.93; 95% confidence interval 0.89-0.96; P <10(-16)). DISCUSSION: MiRNAs have the potential to support AD diagnosis and patient care. PMID- 26806388 TI - Mitochondrial DNA differentiates Alzheimer's disease from Creutzfeldt-Jakob disease. AB - INTRODUCTION: Low content of cell-free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) is a biomarker of early stage Alzheimer's disease (AD), but whether mtDNA is altered in a rapid neurodegenerative dementia such as Creutzfeldt-Jakob disease is unknown. METHODS: CSF mtDNA was measured using digital polymerase chain reaction (dPCR) in two independent cohorts comprising a total of 112 patients diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD), probable AD, or non-Alzheimer's type dementia. RESULTS: Patients with AD exhibit low mtDNA content in CSF compared with patients diagnosed with sCJD or with non-Alzheimer's type dementias. The CSF concentration of mtDNA does not correlate with Abeta, t tau, p-tau, and 14-3-3 protein levels in CSF. DISCUSSION: Low-CSF mtDNA is not a consequence of brain damage and allows the differential diagnosis of AD from sCJD and other dementias. These results support the hypothesis that mtDNA in CSF is a pathophysiological biomarker of AD. PMID- 26806389 TI - Endogenous sex hormones and cognitive function in older women. AB - INTRODUCTION: We examined the association between endogenous sex hormones and both objective and subjective measures of cognitive function. METHODS: We followed 3044 women up to 23 years in a prospective cohort study. We measured plasma levels of estrone, estrone sulfate, estradiol, androstenedione, testosterone, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEA-S) in 1989-1990, conducted neuropsychologic testing in 1999-2008, and inquired about subjective cognition in 2012. RESULTS: Overall, we observed little relation between plasma levels of hormones and either neuropsychologic test performance or subjective cognition. However, after adjustment for age and education, we observed a borderline significant association of higher levels of plasma estrone with higher scores for both overall cognition (P trend = .10) and verbal memory (P trend = .08). DISCUSSION: There were no clear associations of endogenous hormone levels at midlife and cognition in later life, although a suggested finding of higher levels of plasma estrone associated with better cognitive function merits further research. PMID- 26806390 TI - Driving forces for home-based reablement; a qualitative study of older adults' experiences. AB - As a result of the ageing population worldwide, there has been a growing international interest in a new intervention termed 'reablement'. Reablement is an early and time-limited home-based intervention with emphasis on intensive, goal-oriented and interdisciplinary rehabilitation for older adults in need of rehabilitation or at risk of functional decline. The aim of this qualitative study was to describe how older adults experienced participation in reablement. Eight older adults participated in semi-structured interviews. A qualitative content analysis was used as the analysis strategy. Four main themes emerged from the participants' experiences of participating in reablement: 'My willpower is needed', 'Being with my stuff and my people', 'The home-trainers are essential', and 'Training is physical exercises, not everyday activities'. The first three themes in particular reflected the participants' driving forces in the reablement process. Driving forces are intrinsic motivation in interaction with extrinsic motivation. Intrinsic motivation was based on the person's willpower and responsibility, and extrinsic motivation was expressed to be strengthened by being in one's home environment with 'own' people, as well as by the co-operation with the reablement team. The reablement team encouraged and supported the older adults to regain confidence in performing everyday activities as well as participating in the society. Our findings have practical significance for politicians, healthcare providers and healthcare professionals by contributing to an understanding of how intrinsic and extrinsic motivation influence reablement. Some persons need apparently more extrinsic motivational support also after the time-limited reablement period is completed. The municipal health and care services need to consider individualised follow-up programmes after the intensive reablement period in order to maintain the achieved skills to perform everyday activities and participate in society. PMID- 26806391 TI - The cytochrome b5 reductase HPO-19 is required for biosynthesis of polyunsaturated fatty acids in Caenorhabditis elegans. AB - Polyunsaturated fatty acids (PUFAs) are fatty acids with backbones containing more than one double bond, which are introduced by a series of desaturases that insert double bonds at specific carbon atoms in the fatty acid chain. It has been established that desaturases need flavoprotein-NADH-dependent cytochrome b5 reductase (simplified as cytochrome b5 reductase) and cytochrome b5 to pass through electrons for activation. However, it has remained unclear how this multi enzyme system works for distinct desaturases. The model organism Caenorhabditis elegans contains seven desaturases (FAT-1, -2, -3, -4, -5, -6, -7) for the biosynthesis of PUFAS, providing an excellent model in which to characterize different desaturation reactions. Here, we show that RNAi inactivation of predicted cytochrome b5 reductases hpo-19 and T05H4.4 led to increased levels of C18:1n-9 but decreased levels of PUFAs, small lipid droplets, decreased fat accumulation, reduced brood size and impaired development. Dietary supplementation with different fatty acids showed that HPO-19 and T05H4.4 likely affect the activity of FAT-1, FAT-2, FAT-3, and FAT-4 desaturases, suggesting that these four desaturases use the same cytochrome b5 reductase to function. Collectively, these findings indicate that cytochrome b5 reductase HPO-19/T05H4.4 is required for desaturation to biosynthesize PUFAs in C. elegans. PMID- 26806392 TI - MicroRNA transport in cardiovascular complication of diabetes. AB - MicroRNAs (miRNAs) are post-transcriptional inhibitory regulators of gene expression by binding to complementary messenger RNA (mRNA) transcripts. Extracellular miRNAs are transported by membrane-derived vesicles (exosomes and microparticles), lipoproteins, and other ribonucleoprotein complexes. Extracellular microRNAs are emerging as important mediators of intercellular communications, being involved in the transmission of biological signals between cells. Several miRNAs have been identified as having a primary impact on many biological processes that are of direct relevance to cardiovascular complications of diabetes. Whether the extracellular miRNAs are directly involved in the regulation of these processes is yet to be established. Here, we review recent progresses in extracellular miRNA biology and the role of extracellular miRNA in diabetes induced cardiovascular disease, describing the regulators affecting miRNA transport and the mechanisms for different miRNA transporters. In addition, we discuss the advancement of the research in this field and identify the associated challenges. This article is part of a Special Issue entitled: MicroRNAs and lipid/energy metabolism and related diseases edited by Carlos Fernandez-Hernando and Yajaira Suarez. PMID- 26806393 TI - Negative predictive value of procalcitonin in medullary thyroid carcinoma. AB - Calcitonin (CT), the major biochemical marker in medullary thyroid carcinoma (MTC) is prone to in vitro instability and suffers from scarcity of clinical laboratory platforms. Procalcitonin (PCT), the precursor of CT, free of these shortcomings, has been reported as a potential MTC marker. The aim of this study was to assess the negative predictive value (NPV) of PCT as a first-line marker in MTC. 476 serum samples referred to our laboratory for CT measurements were analyzed for PCT. NPVs of PCT were assessed at 3 cut-offs (0.05, 0.10 and 0.15 ng/mL) and the diagnosis of MTC was based on CT levels. PCT and CT levels were correlated (r=0.7554 for CT levels above 10 pg/mL, n=66). Accepting the CT cut off based on the upper reference limit the NPV of PCT were 98.1% (0.05 ng/mL), 96.3% (0.10 ng/mL) and 95.4% (0.15 ng/mL) respectively. For a CT cut-off of 100 pg/mL the NPVs of PCT were 100% for all PCT thresholds. Serum PCT has a strong NPV and could be a good candidate for a first-line screening test to exclude MTC in patients with suspicious thyroid nodules or suggestive symptoms. Larger prospective studies are necessary to confirm our results. PMID- 26806394 TI - Prognostic value of analysing the bioimpedance vector for patients hospitalised for acute decompensated heart failure: A validation cohort. AB - OBJECTIVES: To assess the prognostic impact of the bioimpedance vector (bioelectrical impedance vector analysis [BIVA]) for patients hospitalized for heart failure (HF). MATERIAL AND METHODS: A prospective cohort of 105 patients hospitalized for HF. BIVA was performed prior to discharge, and the final sample was divided into 3 groups according to the value obtained: hyperhydration [hyperH] (>74.3%), normal hydration [normoH] (72.7-74.3%) and dehydration [desH] (<72.7%). In the follow-up, total mortality and readmissions for HF were considered adverse events. RESULTS: A higher incidence of events was observed among the patients with hyperH and desH compared with those with normoH (Kaplan Meier: log-rank, 2.1; p=.04), with an increase in independent risk in the multivariate analysis (HR, 2.6 [1.05-6.44]; p=.039). CONCLUSIONS: BIVA helps stratify the risk of readmission for HF and total mortality in the long-term follow-up of patients hospitalized for HF. PMID- 26806395 TI - Key concepts in community-acquired pneumonia. PMID- 26806396 TI - Up-Down Chair: A novel mechatronic device to assess otolith function in patients with vestibular disorders. AB - This paper describes a novel mechatronic platform, named "Up-Down Chair" (UDC), aimed at investigating otolith function in patients with vestibular disorders. The UDC was designed to provide a wide range of repeatable and controllable vertical oscillations of the head whose kinematic features match those encountered during daily activities. The following parameters were assessed to characterize the performance of the UDC: accordance between expected and measured kinematics in both loaded and unloaded conditions; Dynamic Visual Acuity (DVA) of a group of 15 healthy subjects who were asked to identify a set of Snellen optotypes while being repeatedly moved at different perturbation intensities. Results revealed a good agreement between expected and measured kinematic patterns, and excellent reliability of DVA assessed across enrolled participants. In addition, we observed that the proposed paradigm was effective in inducing oscillopsia in enrolled subjects and that the frequency of the oscillation significantly induced blurred vision during the experimental tests. The UDC appears to be usable as a complementary vestibular clinical test to investigate the effects of therapeutic treatments while applying a wide range of physiological stimuli compatible with those encountered during daily activities. PMID- 26806401 TI - Cardiovascular genetics. PMID- 26806399 TI - Negative pressure wound therapy for the management of flaps with venous congestion. AB - PURPOSE: The aim of this report is to evaluate the utility of negative pressure wound therapy (NPWT) for rescuing flaps with venous congestion not attributable to a mechanical etiology and that cannot be surgically salvaged. PATIENTS AND METHODS: A total of 12 patients suffered from partial or total flap congestion after pedicle or free-flap reconstruction was included. All patients underwent NPWT between 3 and 10 days postoperatively. RESULTS: All congested flaps survived after the application of NPWT. Nine patients suffered partial flap loss and this was addressed through debridement of the devitalized tissue and primary closure. Three patients required blood transfusions during the course of their management. All patients presented complete coverage of the defects without further problems in the flaps after the treatment. CONCLUSION: NPWT may be considered an alternative management strategy for flaps, which has undergone venous congestion not due to a mechanical cause. (c) 2016 Wiley Periodicals, Inc. Microsurgery 36:467-473, 2016. PMID- 26806402 TI - Insight into the light-induced spin crossover of [Fe(bpy)3](2+) in aqueous solution from molecular dynamics simulation of d-d excited states. AB - Molecular dynamics (MD) simulations are performed for d-d excited states of the aqueous [Fe(bpy)3](2+) system using a previously developed model Hamiltonian. Specifically, the characters of d-d excited states and of transitions among these states are explored to gain clues about electronic relaxation during the photo excited metal-to-ligand charge transfer (MLCT) to the lowest quintet d-d states. By evaluating the spin-orbit couplings in various nuclear configurations through MD simulations, strong mixing among low-lying d-d states with different spin multiplicities is found not to be expected in most of the sampled nuclear configurations except for surface crossing regions. The lifetimes of triplet d-d states are evaluated by Fermi's golden rule using equilibrium MD simulations. The internal conversion from upper-lying triplet to lower-lying triplet states is estimated to occur with a lifetime of order 100 fs accompanied by the distortion of the [Fe(bpy)3](2+) complex structure. This result is consistent with the discussion in another computational study, which evaluated the intersystem crossing rates by Fermi's golden rule using electronic structure calculations. In contrast, the present MD simulations cannot provide a clear picture of intersystem crossings from the lowest triplet d-d state after the above-mentioned internal conversion. Based on this result, possible relaxation mechanisms are discussed. PMID- 26806398 TI - Immune-Inflammatory Cell Profile and Receptor Activator of Nuclear Factor Kappa B Ligand/Osteoprotegerin Expression in Persistent Apical Periodontitis after Root Canal Retreatment Failure. AB - INTRODUCTION: This study assessed the immune-inflammatory profile and the expression of bone resorption activators receptor activator of nuclear factor kappa B ligand (RANKL) and inhibitor osteoprotegerin (OPG) in apical periodontitis (n = 20) that persisted after root canal retreatment. METHODS: Immunohistochemistry was used to characterize lymphocyte populations (CD3+, CD45RO+, CD8+, and FoxP3+ cells), macrophages (CD68+), RANKL+ and OPG+ cells in persistent apical periodontitis (PAP) and primary periapical lesions (PPLs). By using quantitative real-time polymerase chain reaction, the mRNA expression of RANKL and OPG in PAP and periodontal ligament from healthy teeth was comparatively analyzed. The data were analyzed by Mann-Whitney, Pearson chi2, and Wilcoxon tests (5% level). RESULTS: PAP showed an elevated number of FoxP3+ cells compared with PPL (P < .001). The number of CD68+ cells was reduced in the PAP samples compared with the PPLs (P < .001). Similar number of other lymphocyte populations was observed in PAP and PPLs (P > .05 for all comparisons). No differences in the RANKL, OPG, and immune-inflammatory cells were demonstrated when comparing PAP microscopically classified as cyst with those classified as granulomas (P > .05 for all comparisons). The assessment of mRNA expression revealed higher levels of RANKL and OPG in PAP compared with the periodontal ligament from healthy teeth (control) samples (P < .001). Also, a greater expression of RANKL in comparison with OPG was observed in PAP (P < .001). CONCLUSIONS: These findings indicate that PAP consists of biologically active lesions that demonstrate potential of bone resorption (higher expression of RANKL) and is characterized by an immune-inflammatory cell profile that suggests a suppressive and regulatory environment (higher number of FoxP3+ cells and lower number of macrophages) favorable to more chronic clinical behavior. PMID- 26806397 TI - PEPCOL: a GERCOR randomized phase II study of nanoliposomal irinotecan PEP02 (MM 398) or irinotecan with leucovorin/5-fluorouracil as second-line therapy in metastatic colorectal cancer. AB - A multicenter, open-label, noncomparative, randomized phase II study (PEPCOL) was conducted to evaluate the efficacy and safety of the irinotecan or PEP02 (MM-398, nanoliposomal irinotecan) with leucovorin (LV)/5-fluorouracil (5-FU) combination as second-line treatment in patients with metastatic colorectal cancer (mCRC). Patients with unresectable mCRC who had failed one prior oxaliplatin-based first line therapy were randomized toirinotecan with LV/5-FU (FOLFIRI) or PEP02 with LV/5-FU (FUPEP; PEP02 80 mg/m(2) with LV 400 mg/m(2) on day 1 and 5-FU 2400 mg/m(2) on days 1-2). Bevacizumab (5 mg/kg, biweekly) was allowed in both arms. The primary endpoint was 2-month response rate (RR). Fifty-five patients were randomized (FOLFIRI, n = 27; FUPEP, n = 28). In the intent-to-treat population (n = 55), 2-month RR response rate was observed in two (7.4%) and three (10.7%) patients in the FOLFIRI and FUPEP arms, respectively. The most common grade 3-4 adverse events reported in the respective FOLFIRI and FUPEP arms were diarrhea (33% vs. 21%), neutropenia (30% vs. 11%), mucositis (11% vs. 11%), and grade 2 alopecia (26% vs. 25%). FUPEP has activity and acceptable safety profile in oxaliplatin-pretreated mCRC patients. PMID- 26806403 TI - Complementary and alternative medicine (CAM) following traumatic brain injury (TBI): Opportunities and challenges. AB - Traumatic brain injury (TBI) is highly prevalent and occurs in a variety of populations. Because of the complexity of its sequelae, treatment strategies pose a challenge. Given this complexity, TBI provides a unique target of opportunity for complementary and alternative medicine (CAM) treatments. The present review describes and discusses current opportunitites and challenges associated with CAM research and clinical applications in civilian, veteran and military service populations. In addition to a brief overview of CAM, the translational capacity from basic to clinical research to clinical practice will be described. Finally, a systematic approach to developing an adoptable evidence base, with proof of effectiveness based on the literature will be discussed. Inherent in this discussion will be the methodological and ethical challenges associated with CAM research in those with TBI and associated comorbidities, specifically in terms of how these challenges relate to practice and policy issues, implementation and dissemination. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID- 26806404 TI - Effects of adenosine metabolism in astrocytes on central nervous system oxygen toxicity. AB - Hyperbaric oxygen (HBO) is widely used in military operations, especially underwater missions. However, prolonged and continuous inhalation of HBO can cause central nervous system oxygen toxicity (CNS-OT), which greatly limits HBO's application. The regulation of astrocytes to the metabolism of adenosine is involved in epilepsy. In our study, we aimed to observe the effects of HBO exposure on the metabolism of adenosine in the brain. Furthermore, we aimed to confirm the possible mechanism underlying adenosine's mediation of the CNS-OT. Firstly, anesthetized rats exposed to 5 atm absolute HBO for 80 min. The concentrations of extracellular adenosine, ATP, ADP, and AMP were detected. Secondly, free-moving rats were exposed to HBO at the same pressure for 20 min, and the activities of 5'-nucleotidase and ADK in brain tissues were measured. For the mechanism studies, we observed the effects of a series of different doses of drugs related to adenosine metabolism on the latency of CNS-OT. Results showed HBO exposure could increase adenosine content by inhibiting ADK activity and improving 5'-nucleotidase activity. And adenosine metabolism during HBO exposure may be a protective response against HBO-induced CNS-OT. Moreover, the improvement of adenosine concentration, activation of adenosine A1R, or suppression of ADK and adenosine A2AR, which are involved in the prevention of HBO-induced CNS-OT. This is the first study to demonstrate HBO exposure regulated adenosine metabolism in the brain. Adenosine metabolism and adenosine receptors are related to HBO-induced CNS-OT development. These results will provide new potential targets for the termination or the attenuation of CNS-OT. PMID- 26806405 TI - Early attempts to visualize cortical monoamine nerve terminals. AB - The Falck-Hillarp, formaldehyde fluorescence method for the demonstration of monoamine neurons in a microscope was established in Lund, Sweden and published in 1962. In the same year Hillarp moved to Karolinska Institutet in Stockholm. Two years later Dahlstrom and Fuxe published the famous supplement in Acta Physiologica Scandinavica, describing the distribution of the dopamine, noradrenaline and serotonin cell groups in the rat brain. This landmark paper also represented an important contribution to an emerging discipline in neuroscience - chemical neuroanatomy. During the following years several modifications of the original method were developed, attempting to solve some shortcomings, one being the reproducible demonstration of noradrenaline nerve terminals in cortical regions. One result was the paper focused on in the present article, which also describes other efforts in the same direction going on in parallel, primarily, in Lund and Stockholm. As a result there was, in the mid 1970s, a fairly complete knowledge of the catecholamine systems in the rat brain. This article is part of a Special Issue entitled SI:50th Anniversary Issue. PMID- 26806406 TI - A Novel Tool for Evaluation of Mild Traumatic Brain Injury Patients in the Emergency Department: Does Robotic Assessment of Neuromotor Performance Following Injury Predict the Presence of Postconcussion Symptoms at Follow-up? AB - OBJECTIVES: Postconcussion symptoms (PCS) are a common complication of mild traumatic brain injury (TBI). Currently, there is no validated clinically available method to reliably predict at the time of injury who will subsequently develop PCS. The purpose of this study was to determine if PCS following mild TBI can be predicted during the initial presentation to an emergency department (ED) using a novel robotic-assisted assessment of neurologic function. METHODS: All patients presenting to an urban ED with a chief complaint of head injury within the preceding 24 hours were screened for inclusion from March 2013 to April 2014. The enrollment criteria were as follows: 1) age of 18 years or greater, 2) ability and willingness to provide written informed consent, 3) blunt head trauma and clinical diagnosis of isolated mild TBI by the treating physician, and 4) blood alcohol level of <100 mg/dL. Eligible mild TBI patients were enrolled and their neuromotor function was assessed in the ED using a battery of five tests that cover a range of proprioceptive, visuomotor, visuospatial, and executive function performance metrics. At 3 weeks postinjury, participants were contacted via telephone to complete the Rivermead Post-Concussion Symptoms Questionnaire to assess the presence of significant PCS. RESULTS: A total of 66 mild TBI patients were enrolled in the study with 42 of them completing both the ED assessment and the follow-up; 40 patients were included in the analyses. The area under the receiver operating characteristic curve (AUC) for the entire test battery was 0.72 (95% confidence interval [CI] = 0.54 to 0.90). The AUC for tests that primarily measure visuomotor and proprioceptive performance were 0.80 (95% CI = 0.65 to 0.95) and 0.71 (95% CI = 0.53 to 0.89), respectively. CONCLUSIONS: The robotic-assisted test battery has the ability to discriminate between subjects who developed PCS and those who did not. Additionally, poor visuomotor and proprioceptive performance were most strongly associated with subsequent PCS. PMID- 26806408 TI - Bifunctional bioceramics stimulating osteogenic differentiation of a gingival fibroblast and inhibiting plaque biofilm formation. AB - Gingival recession is a common clinical problem that results in esthetic deficiencies and poor plaque control and predominantly occurs in aged patients. In order to restore the cervical region, ideal biomaterials should possess the ability to stimulate proliferation and osteogenesis/cementogenesis of human gingival fibroblasts (HGF) and have a strong antibiofilm effect. The aim of the present study was to investigate the interactions of HGF and oral multispecies biofilms with Ca, Mg and Si-containing bredigite (BRT, Ca7MgSi4O16) bioceramics. BRT extract induced osteogenic/cementogenic differentiation of HGF and its inhibition of plaque biofilm formation were systematically studied. BRT extract in concentrations lower than <200 mg mL(-1) presented high biocompatibility to HGF cells in 3 days. Ion extracts from BRT also stimulated a series of bone related gene and protein expressions in HGF cells. Furthermore, BRT extract significantly inhibited oral multispecies plaque biofilm growth on its surface and contributed to over 30% bacterial cell death without additional antibacterial agents in two weeks. A planktonic killing test showed that BRT suppressed 98% plaque bacterial growth compared to blank control in 3 days. The results also revealed that BRT extract has an osteostimulation effect on HGF. The suppression effect on plaque biofilms suggested that BRT might be used as a bioactive material for cervical restoration and that the synergistic effect of bioactive ions, such as Ca, Mg and Si ions, played an important role in the design and construction of bifunctional biomaterials in combination with tissue regeneration and antibiofilm activity. PMID- 26806409 TI - Down-regulation of OsSPX1 caused semi-male sterility, resulting in reduction of grain yield in rice. AB - OsSPX1, a rice SPX domain gene, involved in the phosphate (Pi)-sensing mechanism plays an essential role in the Pi-signalling network through interaction with OsPHR2. In this study, we focused on the potential function of OsSPX1 during rice reproductive phase. Based on investigation of OsSPX1 antisense and sense transgenic rice lines in the paddy fields, we discovered that the down-regulation of OsSPX1 caused reduction of seed-setting rate and filled grain number. Through examination of anthers and pollens of the transgenic and wild-type plants by microscopy, we found that the antisense of OsSPX1 gene led to semi-male sterility, with lacking of mature pollen grains and phenotypes with a disordered surface of anthers and pollens. We further conducted rice whole-genome GeneChip analysis to elucidate the possible molecular mechanism underlying why the down regulation of OsSPX1 caused deficiencies in anthers and pollens and lower seed setting rate in rice. The down-regulation of OsSPX1 significantly affected expression of genes involved in carbohydrate metabolism and sugar transport, anther development, cell cycle, etc. These genes may be related to pollen fertility and male gametophyte development. Our study demonstrated that down regulation of OsSPX1 disrupted rice normal anther and pollen development by affecting carbohydrate metabolism and sugar transport, leading to semi-male sterility, and ultimately resulted in low seed-setting rate and grain yield. PMID- 26806410 TI - Structure and Function of CW Domain Containing Proteins. AB - The CW domain is a zinc binding domain, composed of approximately 50- 60 amino acid residues with four conserved cysteine (C) and two to four conserved tryptophan (W) residues. The members of the superfamily of CW domain containing proteins, comprised of 12 different eukaryotic nuclear protein families, are extensively expressed in vertebrates, vertebrate-infecting parasites and higher plants, where they are often involved in chromatin remodeling, methylation recognition, epigenetic regulation and early embryonic development. Since the first CW domain structure was determined 5 years ago, structures of five CW domains have been solved so far. In this review, we will discuss these recent advances in understanding the identification, definition, structure, and functions of the CW domain containing proteins. PMID- 26806411 TI - Craving and Withdrawal Symptoms During Smoking Cessation: Comparison of Pregnant and Non-Pregnant Smokers. AB - Although pregnant smokers are aware of the negative peri- and postnatal health consequences of smoking, the cessation rate in pregnancy is low, raising the question of why pregnant smokers have difficulty quitting. Reasons might be that pregnant smokers experience more intense craving and withdrawal symptoms than non pregnant smokers. We compared craving and withdrawal in 306 pregnant smokers versus 93 non-pregnant women using data from two smoking cessation trials. Complete data were analyzed using pre-quit and post-quit (2 weeks after quit date) craving and withdrawal measured by the 12-item French Tobacco Craving Questionnaire (FTCQ-12) and French Minnesota Nicotine Withdrawal Scale (FMNWS). Pregnant smokers started smoking and smoked regularly earlier and succeeded far less at quitting smoking by week 2 than the general population of smokers (11% versus 43%). Post-quit date FTCQ-12 general score was higher in pregnant smokers compared to comparison groups, and was driven by elevated emotionality and expectancy. FMNWS decreased significantly less among pregnant smokers than among non-pregnant smokers. Insufficient reduction of craving and withdrawal symptoms in response to a quit attempt may partially explain why pregnant smokers may have more difficulty quitting than non-pregnant smokers. Because this was a historical comparison, findings are preliminary; however, they might foster further investigation of differences in craving and withdrawal symptoms in pregnant versus non-pregnant smokers. PMID- 26806413 TI - Cancer genomics: A nucleosome footprint reveals the source of cfDNA. PMID- 26806414 TI - Epigenomics: Parallel single-cell sequencing. PMID- 26806412 TI - Single-cell genome sequencing: current state of the science. AB - The field of single-cell genomics is advancing rapidly and is generating many new insights into complex biological systems, ranging from the diversity of microbial ecosystems to the genomics of human cancer. In this Review, we provide an overview of the current state of the field of single-cell genome sequencing. First, we focus on the technical challenges of making measurements that start from a single molecule of DNA, and then explore how some of these recent methodological advancements have enabled the discovery of unexpected new biology. Areas highlighted include the application of single-cell genomics to interrogate microbial dark matter and to evaluate the pathogenic roles of genetic mosaicism in multicellular organisms, with a focus on cancer. We then attempt to predict advances we expect to see in the next few years. PMID- 26806415 TI - Nanotools and molecular techniques to rapidly identify and fight bacterial infections. AB - Reducing the emergence and spread of antibiotic-resistant bacteria is one of the major healthcare issues of our century. In addition to the increased mortality, infections caused by multi-resistant bacteria drastically enhance the healthcare costs, mainly because of the longer duration of illness and treatment. While in the last 20years, bacterial identification has been revolutionized by the introduction of new molecular techniques, the current phenotypic techniques to determine the susceptibilities of common Gram-positive and Gram-negative bacteria require at least two days from collection of clinical samples. Therefore, there is an urgent need for the development of new technologies to determine rapidly drug susceptibility in bacteria and to achieve faster diagnoses. These techniques would also lead to a better understanding of the mechanisms that lead to the insurgence of the resistance, greatly helping the quest for new antibacterial systems and drugs. In this review, we describe some of the tools most currently used in clinical and microbiological research to study bacteria and to address the challenge of infections. We discuss the most interesting advancements in the molecular susceptibility testing systems, with a particular focus on the many applications of the MALDI-TOF MS system. In the field of the phenotypic characterization protocols, we detail some of the most promising semi-automated commercial systems and we focus on some emerging developments in the field of nanomechanical sensors, which constitute a step towards the development of rapid and affordable point-of-care testing devices and techniques. While there is still no innovative technique that is capable of completely substituting for the conventional protocols and clinical practices, many exciting new experimental setups and tools could constitute the basis of the standard testing package of future microbiological tests. PMID- 26806416 TI - European Spirometry Driving License in Poland--first Polish spirometry training in the framework of ERS HERMES Spirometry project. PMID- 26806418 TI - Pulmonary lesions in the course of gastric cancer--two cases of Bard's syndrome. AB - The Bard's syndrome is a medical condition related to miliary dissemination of gastric cancer to the lungs. Difficulties in diagnosis are associated with the need of differentiation between numerous diseases, which may manifest as disseminated lesions in the lung parenchyma on chest X-ray. Despite the advanced proliferative process, primary focus of neoplasm frequently remains subclinical. Metastatic lesions cause many symptoms in the respiratory system, suggesting primary pulmonary pathology. The Bard's syndrome should be always taken into account in differential diagnosis of disseminated lesions, particularly due to prevalence of gastric cancer. The study presents two cases of patients with disseminated pulmonary lesions, corresponding to gastric cancer metastases on radiological imaging. PMID- 26806417 TI - Typing safe antibiotics in amoxicillin hypersensitive patients--development of a stepwise protocol. AB - INTRODUCTION: A history of an adverse reaction to amoxicillin, irrespective of the mechanism involved, significantly elevates patients' anxiety and affects therapeutic decisions in the future, leading to unnecessary avoidance of antibiotics. As a consequence, it would be useful to find a safe and reliable protocol for typing safe alternative antibiotics. The aim of the study was to determine negative predictive value of typing safe antibiotic in patients with a history of hypersensitivity reaction to amoxicillin. MATERIAL AND METHODS: 71 patients, aged 20-83, with a history of an adverse reaction to amoxicillin were retrospectively analysed. On the basis of the reaction type they were divided into three groups: A - symptoms not typical for hypersensitivity reactions, B - allergy manifested by urticaria and/or angioedema, C - anaphylaxis. In group A amoxicillin was tested, in group B - cefuroxime, and in group C - macrolide: azithromycin or clarithromycin. Telephone follow-up visits were performed twice: 6-12 months and 3-5 years after the clinical assessment to evaluate tolerance of antibiotics. On the basis of the follow-up results, the negative predictive value (NPV) of the protocol was calculated. RESULTS: The full diagnostic protocol was applied in 62 participants. Amoxicillin was found safe in 22, cefuroxime - in 21 and macrolide - in 19 patients. No anaphylactic reactions were observed during the tests. On the basis of the telephone follow-up, the NPV of the protocol was 96% in the first follow-up and 97% in the second one. CONCLUSION: A stepwise approach including SPTs, ICTs and provocations with amoxicillin / cefuroxime/macrolide - depending on a patient's history - is safe and allows typing an antibiotic in the vast majority of patients. PMID- 26806420 TI - Identification and Organoleptic Contribution of Vanillylthiol in Wines. AB - Vanillylthiol, a chemical compound reminiscent of clove and smoke, has been identified for the first time in young red and dry white wines. The chemical structure of this new aroma was confirmed by original chemical synthesis. Vanillylthiol was prepared by a two-step procedure from vanillin. The conversion of vanillin to divanillyl disulfide was easily achieved by treatment with an inorganic sulfur-donor reagent. Reduction of the disulfide gave the target thiol in good yield. The quantification of vanillylthiol in wine was performed by nonspecific liquid/liquid extraction (CH2Cl2), separation of the volatile compounds using gas chromatography, and specific detection using tandem mass spectrometry (triple quadrupole). Vanillylthiol was found particularly in young wines aged in new oak barrels. These wines contained between a few 50 ng/L to more than 8300 ng/L. The highest levels were found in red wines aged 12 months in new oak barrels. Given its perception threshold in a wine model solution (3.8 MUg/L), vanillylthiol may contribute to the spicy, clove-like flavor of red wines aged in oak barrels. PMID- 26806421 TI - Time-lapse monitoring reveals that vitrification increases the frequency of contraction during the pre-hatching stage in mouse embryos. AB - Contraction during the blastocyst stage is observed during embryonic development of various mammals, including humans, but the physiological role of this process is not well understood. Using time-lapse monitoring (TLM), we studied the influence of vitrification and contractions on embryonic development in mice. Mouse embryos were cultured at the 2-cell stage. At the 8-cell stage, embryos were randomly divided into a fresh group (FG) and vitrified group (VG) and observed for up to 144 h. Strong contractions (i.e., contractions causing a decrease in volume of more than 20% and expansion of the perivitelline space) occurred significantly more often in unhatched embryos than hatching embryos in both groups. Regarding hatching embryos, contractions in the pre-hatching stage were significantly more frequent in the VG than the FG. Furthermore, mRNA expression levels of genes related to contractions were determined at three time points, the 8-cell stage, early blastocyst stage, and 20 h after blastocoel formation, with quantitative reverse transcription-polymerase chain reaction. There was no significant difference in Hspa1a expression between the FG and VG, but Hspa1a overexpression was observed just after thawing and tended to decrease gradually thereafter in some blastocysts. Furthermore, in the VG, Atp1a1 tended to show higher expression in the strong contraction group than in the weak contraction group. Overall, vitrification is an excellent method for cryopreservation but could increase contractions in the pre-hatching stage and may increase energy demands of the embryo. Observation of contraction by TLM may improve the evaluation of embryo quality. PMID- 26806422 TI - Use of Serial Quantitative PCR of the vapA Gene of Rhodococcus equi in Feces for Early Detection of R. equi Pneumonia in Foals. AB - BACKGROUND: Current screening tests for Rhodococcus equi pneumonia in foals lack adequate accuracy for clinical use. Real-time, quantitative PCR (qPCR) for virulent R. equi in feces has not been systematically evaluated as a screening test. OBJECTIVE: The objective of this study was to evaluate the accuracy of qPCR for vapA in serially collected fecal samples as a screening test for R. equi pneumonia in foals. ANIMALS: One hundred and twenty-five foals born in 2011 at a ranch in Texas. METHODS: Fecal samples were collected concurrently with thoracic ultrasonography (TUS) screening examinations at ages 3, 5, and 7 weeks. Affected (pneumonic) foals (n = 25) were matched by age and date-of-birth to unaffected (n = 25) and subclinical (ie, having thoracic TUS lesions but no clinical signs of pneumonia) foals (n = 75). DNA was extracted from feces using commercial kits and concentration of virulent R. equi in feces was determined by qPCR. RESULTS: Subsequently affected foals had significantly greater concentrations of vapA in feces than foals that did not develop pneumonia (unaffected and subclinical foals) at 5 and 7 weeks of age. Accuracy of fecal qPCR, however, was poor as a screening test to differentiate foals that would develop clinical signs of pneumonia from those that would remain free of clinical signs (including foals with subclinical pulmonary lesions attributed to R. equi) using receiver operating characteristic (ROC) methods. CONCLUSIONS AND CLINICAL IMPORTANCE: In the population studied, serial qPCR on feces lacked adequate accuracy as a screening test for clinical R. equi foal pneumonia. PMID- 26806423 TI - Comments regarding: Lucchetti MC, Fratto G, Valeriani F, De Vittori E, Giampaoli S, Papetti P, et al. Cobalt-chromium alloys in dentistry: An evaluation of metal ion release. J Prosthet Dent 2015;114:602-8. PMID- 26806424 TI - Chondroitin sulfate beta-1,4-N-acetylgalactosaminyltransferase-1 (ChGn-1) polymorphism: Association with progression of multiple sclerosis. AB - Chondroitin sulfate proteoglycans (CSPGs) are a constituent of the matrix of the central nervous system (CNS), likely participating as regulatory molecules in the process of demyelination, remyelination, axonal degeneration and regeneration in the CNS. ChGn-1 is a key enzyme for production of CSPGs and knock-out mice of this gene showed better recovery from spinal cord injury. We hypothesized that the clinical course of multiple sclerosis (MS) is influenced by the level of expression of ChGn-1 gene. We recruited 147 patients with MS and 181 healthy control subjects and analyzed single nucleotide polymorphisms (SNPs) of this gene. We found the coding SNP (cSNP: rs140161612) in approximately 10% of patients with MS as well as normal controls. The cSNP is changed from serine to leucine at position 126 (p.S126L). The expressed ChGn-1 mutant proteins exhibited no enzyme activities in COS-1 cells. In men, patients who had MS with S126L had a slower disease progression. This cSNP might be associated with the sex differences in clinical course of MS. PMID- 26806425 TI - Bringing light into the dark side of identity: theoretical and clinical applications: a case study. AB - In the final part, a clinical reflection is presented on the dark side of identity formation and the empirical papers of this special issue. It is important that both researchers and clinicians ask themselves how theory and evidence about identity development can be used in clinical practice. Therefore, a relevant case study is presented about an emerging adult struggling with identity formation, Tim. Various facets of Tim's struggling are illustrated based on findings from this special issue. Starting from identity diffusion, Tim's transition to moratorium and achievement was examined from three complementary theoretical frameworks and related research on these topics as outlined in this special issue. Finally, change processes throughout therapy were discussed from various clinical frameworks. PMID- 26806428 TI - The lower medial thigh perforator (LMTP) flap for lower extremity reconstruction: Preliminary results. AB - BACKGROUND: The lower medial thigh perforator (LMTP) flap is an alternative source for lower extremity reconstruction. In this article, we report the preliminary results of reconstruction of the lower extremity with a series of patients by the lower medial thigh perforator flap. PATIENTS AND METHODS: From January 2015 until August 2015, we performed six cases of lower extremity reconstruction with the LMTP flap. The defect locations included the distal leg (1 case) and the proximal leg (2 cases), the left foot (2 cases), and the right foot (1 case). The perforators of the flap design were detected at the distal third of the line, which was drawn from the midpoint of inguinal ligament to medial upper border of patella. The dorsalis pedis artery (2 cases), anterior tibia artery (2 cases), posterior tibial artery (2 cases) were dissected as recipient vessels. RESULTS: The average size of flap was 10.5 * 5 cm (range 10-15 cm and 4-6.5 cm), and the average pedicle length was 7.6 cm (range 5-9.5 cm). 83% of the perforators (5 of 6) were musculocutaneous type, and 17% (1 of 6) were septocutaneous type. The flap survival rate was 100%; the venous congestion was observed in one flap and was successfully salvaged by performing revised venous anastomosis. The donor sites were all closed primarily with minimal morbidity. Follow-up observations were conducted for 2-6 months, and all patients had good functional recovery with satisfactory cosmetic results. CONCLUSION: The lower medial thigh perforator flap has some advantage in lower extremity reconstruction, including adequate length and vessel diameter of pedicle for microvascular anastomosis to the lower extremities recipient vessels. The LMTP flap indicates a low donor-site morbidity and it could be a safe, reliable, and aesthetically appealing new option for lower extremity reconstruction. (c) 2016 Wiley Periodicals, Inc. Microsurgery 36:474-479, 2016. PMID- 26806429 TI - Head-to-Head Comparison of Ultra-High-Performance Liquid Chromatography with Diode Array Detection versus Quantitative Nuclear Magnetic Resonance for the Quantitative Analysis of the Silymarin Complex in Silybum marianum Fruit Extracts. AB - Quantitative nuclear magnetic resonance (qNMR) spectroscopy is known as an excellent alternative to chromatography-based mixture analysis. NMR spectroscopy is a non-destructive method, needs only limited sample preparation, and can be readily automated. A head-to-head comparison of qNMR to an ultra-high-performance liquid chromatography with diode array detection (uHPLC-DAD)-based quantitative analysis of six flavonolignan congeners (silychristin, silydianin, silybin A, silybin B, isosilybin A, and isosilybin B) of the Silybum marianum silymarin complex is presented. Both assays showed similar performance characteristics (linear range, accuracy, precision, and limits of quantitation) with analysis times below 30 min/sample. The assays were applied to industrial S. marianum extracts (AC samples) and to extracts locally prepared from S. marianum fruits (PL samples). An assay comparison by Bland-Altman plots (relative method bias AC samples, -0.1%; 2SD range, +/-5.1%; relative method bias PL samples, -0.3%; 2SD range, +/-7.8%) and Passing-Bablok regression analysis (slope and intercept for AC and PL samples not significantly different from 1.00 and 0.00, respectively; Spearman's coefficient of rank correlation, >0.99) did show that qNMR and uHPLC DAD can be used interchangeably to quantitate flavonolignans in the silymarin complex. PMID- 26806430 TI - Whole-genome sequencing of the endangered bovine species Gayal (Bos frontalis) provides new insights into its genetic features. AB - Gayal (Bos frontalis) is a semi-wild and endangered bovine species that differs from domestic cattle (Bos taurus and Bos indicus), and its genetic background remains unclear. Here, we performed whole-genome sequencing of one Gayal for the first time, with one Red Angus cattle and one Japanese Black cattle as controls. In total, 97.8 Gb of sequencing reads were generated with an average 11.78-fold depth and >98.44% coverage of the reference sequence (UMD3.1). Numerous different variations were identified, 62.24% of the total single nucleotide polymorphisms (SNPs) detected in Gayal were novel, and 16,901 breed-specific nonsynonymous SNPs (BS-nsSNPs) that might be associated with traits of interest in Gayal were further investigated. Moreover, the demographic history of bovine species was first analyzed, and two population expansions and two population bottlenecks were identified. The obvious differences among their population sizes supported that Gayal was not B. taurus. The phylogenic analysis suggested that Gayal was a hybrid descendant from crossing of male wild gaur and female domestic cattle. These discoveries will provide valuable genomic information regarding potential genomic markers that could predict traits of interest for breeding programs of these cattle breeds and may assist relevant departments with future conservation and utilization of Gayal. PMID- 26806431 TI - Vertebral level and measurements of conus medullaris and dural sac termination with special reference to the apex of the sacral hiatus: anatomical and magnetic resonance imaging radiologic study. AB - BACKGROUND: Anatomical orientation of the caudal space and termination level of conus medullaris (CMT) and dural sac (DST) has great significance for anaesthetists and neurosurgeons. This study aimed to explore the anatomical landmarks important to perform save spinal anaesthesia, lumber puncture and caudal analgesia through the correlation between the vertebral level of CMT, DST and sacral hiatus apex (SHA) in human cadavers and by using magnetic resonance imaging (MRI). MATERIALS AND METHODS: Sixty adult cadavers (40 males, 20 females) and 200 (100 males, 100 females) MR lumbosacral images of 16-69-year-old persons were used in this study. Vertebral level of CMT, DST and SHA and their linear distances were determined in cadavers and MRI. Also, anteroposterior diameter at SHA, length and thickness of sacrococcygeal membrane were measured as well, and correlate these levels and their distances with age and sex. RESULTS: Mean and highest frequent number of MRI vertebral level of CMT was observed at lower third of L1 in men and L1-2 disc in women, that of DST at upper third of S2 in men and middle third of S2 in women, while SHA was seen at middle third of S4 in both men and women with no significant (p > 0.05) age or gender differences. In 5% of cases, CMT, DST and SHA were seen at vertebral level below L2, below S2-3 and above S3, respectively. However, mean vertebral level of CMT, DST, SHA was observed at L1L, S2M and S4U without sex differen-ce in cadaveric specimens, respectively. All linear distances of men MRI revealed significant difference (p < 0.05) compared with those of women except thickness of sacrococcygeal membrane and anterposterior diameter at SHA. CONCLUSIONS: Accurate knowledge of vertebral level of CMT, DST and SHA and the distances in-between might decrease the iatrogenic injury of dural sac, spinal cord and cauda equina. PMID- 26806432 TI - Craniofacial structure in patients with obstructive sleep apnoea. AB - BACKGROUND: Obstructive sleep apnoea (OSA) is characterised by at least five 10-s episodes of apnoea or markedly shallow breathing per 1 h of sleep, which can lead to severe, sometimes life-threatening complications. It is essential to determine the specific features of the affected patients' craniofacial structure, thus enabling their allocation to risk groups. The aim of the study was to assess the craniofacial structure in OSA patients, comparing the findings with Hasund's and Segner's cephalometric normal values. In addition, the sagittal dimensions of the upper airways, measured at two levels, were compared to McNamara's normal values. MATERIALS AND METHODS: The study covered 41 patients diagnosed polysomno graphically with OSA. Lateral cephalograms with cephalometric analysis and the measurements of the upper and lower sagittal dimensions of the upper airways were taken for each patient. RESULTS: The only feature of the patents' facial skeleton that significantly diverged from the normal range was the SNB angle (p = 0.004). Other angles, i.e. SNA, ANB, NL/NSL, NL/ML and NSL/ML, were not significantly different from normal. The average upper cross-sectional area of the upper airways was 10.4 mm; in 97.6% patients, this measurement was below McNamara's normal values. In the majority of patients (75.6%), the average lower sagittal dimension of the upper airways (10.4 mm) was also below the normal. CONCLUSIONS: Mandibular retrognathia, manifested by the reduced SNB angle, and the narrowed upper and lower sagittal dimensions of the upper airways can be considered one of OSA prognostic factors. PMID- 26806433 TI - Interstitial cells of Cajal - systematic review. AB - This paper reviews the distribution of interstitial cells of Cajal (ICC) in the human gastro-intestinal (GI) tract, based on ultrastructural and immunohistochemical evidence. The distribution and morphology of ICC at each level of the normal GI tracts is addressed from the perspective of their functional significance. Alterations of ICC reported in as well as in GI stromal tumours are reviewed, with emphasis on the place of ICC in the pathophysiology of disease. PMID- 26806434 TI - The impact of type 1 diabetes on the development of the craniofacial mineralised tissues (bones and teeth): literature review. AB - BACKGROUND: There are many reports on the impact of diabetes on periodontium as well as the state of organs in diabetics; however, there is little research on the impact of the disease on morphological and anatomical changes in the mineralised tissues like teeth and craniofacial bones. The aim of this study was to present a review of literature on morphological and anatomical changes of mineralised tissues in the course of type 1 diabetes. MATERIALS AND METHODS: A review of PubMed database was made using the keywords: morphological changes, anatomical changes, enamel hypoplasia, type 1 diabetes, induced diabetes and the names of individual anatomical and morphological structures of the teeth. RESULTS: The analysis of experimental studies have shown that in induced type 1 diabetes in rats there is a substantial reduction in the thickness of the enamel and dentin, compared with the control group. The changes in the content of indivi dual minerals in the tissues of the tooth have been shown - a decrease in the concentration of calcium and fluoride ions and an increase in the concentration of magnesium. In a study conducted on embryos of rats born of diabetic dams, defects were observed in enamel organ, which can cause delayed enamel hypo plasia. Literature analysis revealed morphological disorders also in some clinical cases of patients with type 1 diabetes. CONCLUSIONS: Type 1 diabetes mellitus as a metabolic disorder may affect changes in the structure of mineralised tissues, thereby increasing their susceptibility to caries development and orthognathic disorders. PMID- 26806436 TI - How does self stigma differ across people with psychiatric diagnoses and rheumatoid arthritis, and how does it impact on self-esteem and empowerment? AB - Self stigmatising attitudes have been found in people who have psychiatric diagnoses, however, research assessing self stigma in physical illnesses is rare. It is known that receiving a diagnosis of rheumatoid arthritis (RA) can affect a person's identity and self esteem. This study aimed to compare levels of self stigma, self esteem and empowerment between people diagnosed with psychiatric illnesses and people diagnosed with RA to establish whether self stigma, and specifically endorsement of negative stereotypes, is associated with self esteem and empowerment across these two groups. A total of 202 participants (psychiatric group n = 102; RA group n = 100) were interviewed using the Internalised Stigma of Mental Illness scale (ISMI), or the Internalized Stigma of Mental Illness scale- Rheumatoid Arthritis (ISMI-RA), the Index of Self Esteem (ISE) and the Mental Health Confidence Scale (MHCS). Overall, the psychiatric group had higher self stigma scores (2.5 vs. 2.2, p < .01), lower self esteem (48.7 vs. 36.8, p < .001) and lower empowerment scores (3.8 vs. 4.3, p < .001) than the RA group. However, sizable proportions of both groups had high self stigma scores. ISMI/ISMI-RA was associated with the ISE and the MHCS. The stereotype endorsement subscale of the ISMI/ISMI-RA was not related to self esteem or empowerment in either group. Interventions that aim to decrease self stigma and increase self esteem could focus on alienation. PMID- 26806435 TI - Donor-specific antibodies after pediatric liver transplantation: a cross sectional study of 50 patients. AB - The role of donor-specific HLA antibodies (DSAs) after pediatric liver transplantation (LT) is inadequately established. We conducted a cross-sectional study on the prevalence of DSAs and their association with liver histology and biochemical variables after pediatric LT. Serum samples were drawn for HLA antibody analyses from 50 patients (76% of 66 eligible patients) operated on at age <18 years between 1987 and 2007 with a median of 10.0 (interquartile range 4.0-16.4) years after deceased donor LT. Mixed and single-antigen beads with Luminex were used for HLA antibody screening and detection. A mean fluorescence intensity (MFI) value of 1000 was used for positive cutoff. Twenty-six patients (52%; 95% confidence interval (CI) 39% to 65%) had DSAs. In 22 (85%) patients, DSAs were against class II HLA antigens with a mean (standard deviation) MFI of 13,481 (4727). The unadjusted prevalence ratio for portal inflammation in DSA positive compared to DSA-negative patients (n = 47; 9/24 vs. 1/23) was 8.6 (95% CI 1.6 to 50.9). Laboratory values at the time of study were comparable between DSA-positive and DSA-negative patients. In conclusion, approximately half of patients studied had DSAs after pediatric LT. Portal inflammation was associated with DSA positivity although the wide confidence interval around the ratio estimate warrants cautious interpretation. PMID- 26806437 TI - Acute pancreatitis in elderly patients: A retrospective evaluation at hospital admission. AB - BACKGROUND AND AIMS: Acute pancreatitis (AP) in elderly may have an aggressive course due to co-morbidity high rate and severe presentation. We retrospectively evaluated AP severity and its underlying factors in a group of elderly patients compared with an adult population sample. METHODS: Forty-two elderly patients (65 102years) and 48 controls (19-64years) admitted at our Unit for biliary or alcoholic AP were retrospectively enrolled. AP severity was evaluated by the Atlanta classification and Ransom score. Laboratory investigations and demographic data were collected. Comparison between the two groups was performed by t-test, ANOVA or Fisher's exact test. A multinomial logistic regression was used to determine factors affecting AP severity. RESULTS: Elderly patients showed more severe Atlanta (1.81+/-0.75 vs 1.29+/-0.46; p=0.007) and higher Ransom (2.52+/-1.57 vs 0.75+/-0.73; p<0.0001) scores. No death was observed. Elderly patients consumed more drugs than controls, had higher rates of cardiovascular, pulmonary and renal co-morbidity, showed higher creatinine (1.09+/-0.41 vs 0.81+/ 0.18; p=0.004) and lower calcium levels (8.43+/-0.48 vs 8.88+/-0.44; p=0.002). We observed only one case of fluid necrosis in an old patient. Non-necrotic fluid collections were more common in the elderly (40.5% vs 12.5%; p=0.003). At multivariate analysis, AP severity was influenced by white blood cell-count (WBC: OR=1.94; p=0.048), aspartate-transaminase-levels (AST: OR=1.97; p=0.02), serum lactate-dehydrogenase (LDH: OR=1.07; p=0.047) and Ransom score (OR=70.4; p=0.036) in elderly, while only Ransom score correlated in controls (OR=66.04; p<0.001). The etiology (biliary/alcoholic) did not influence the severity. CONCLUSIONS: Elderly patients usually undergo a severe AP course, but without increase of mortality. High WBC, LDH, AST and Ransom score at the onset may predict AP severity. PMID- 26806438 TI - Movement disorders induced by deep brain stimulation. AB - Deep brain stimulation represents a major advance in the treatment of several types of movement disorders. However, during stimulation new movement disorders may emerge, thus limiting the positive effects of this therapy. These movement disorders may be induced by: 1) stimulation of the targeted nucleus, 2) stimulation of surrounding tracts and nuclei, and 3) as a result of dose adjustment of accompanying medications, such as reduction of dopaminergic drugs in patients with Parkinson's disease. Various dyskinesias, blepharospasm, and apraxia of eyelid opening have been described mainly with subthalamic nucleus stimulation, whereas hypokinesia and freezing of gait have been observed with stimulation of the globus pallidus internus. Other deep brain stimulation-related movement disorders include dyskinesias associated with stimulation of the globus pallidus externus and ataxic gait as a side effect of chronic bilateral stimulation of the ventral intermediate nucleus of thalamus. These movement disorders are generally reversible and usually resolved once the stimulation is reduced or turned off. This, however, typically leads to loss of benefit of the underlying movement disorder which can be re-gained by using different contacts, changing targets or stimulation parameters, and adjusting pharmacological therapy. New and innovative emerging technologies and stimulation techniques may help to prevent or overcome the various deep brain stimulation-induced movement disorders. In this review we aim to describe the clinical features, frequency, pathophysiology, and strategies for treatment of these iatrogenic movement disorders. PMID- 26806439 TI - A New Class of Phantom Materials for Poroelastography Imaging Techniques. AB - Poroelastography is an elastographic technique used to image the temporal mechanical behavior of tissues. One of the major challenges in determining experimental potentials and limitations of this technique has been the lack of complex and realistic controlled phantoms that could be used to corroborate the limited number of theoretical and simulation studies available in the literature as well as to predict its performance in complex experimental situations and in a variety of conditions. In the study described here, we propose and analyze a new class of phantom materials for temporal elastography imaging. The results indicate that, by using polyacrylamide, we can generate inhomogeneous elastographic phantoms with controlled fluid content and fluid flow properties, while maintaining mechanical and ultrasonic properties similar to those of soft tissues. PMID- 26806440 TI - Contrast-Enhanced Ultrasonography of Pancreatic Carcinoma: Correlation with Pathologic Findings. AB - We concluded that contrast-enhanced ultrasound (CEUS) has clinical value in identifying the pathologic changes of pancreatic carcinomas. Forty-three patients diagnosed with pancreatic carcinoma through surgery were retrospectively investigated. CEUS examinations were performed on all patients before surgery. Enhancement patterns on CEUS were observed. Time-intensity curves of CEUS were generated for the regions of interest in the pancreas, and quantitative parameters were obtained. Resected cancer specimens were stained with hematoxylin and eosin for histologic analysis, and the microvascular density (MVD) of the specimens was determined by CD34 immunohistochemical staining. Enhancement patterns of CEUS were compared with histopathologic findings in pancreatic carcinomas. Correlations between time-intensity curve parameters and microvascular density were analyzed. Twenty cases manifested centripetal enhancement, and 23 cases, global enhancement. The amount of tumor necrosis or mucus in the centripetally enhanced pancreatic carcinomas was greater than that in the globally enhanced pancreatic carcinomas (p = 0.027). Thirty-eight of 43 (88.4%) pancreatic carcinomas manifested hypo-enhancement with a maximum intensity (IMAX) <90%. Contrast arrival time in pancreatic carcinoma was longer than that in adjacent pancreatic tissue (p < 0.05). IMAX was positively correlated with microvascular density (r = 0.577, p < 0.05). We concluded that CEUS manifestations could reflect the histologic changes of pancreatic carcinomas and CEUS can be used to evaluate blood perfusion of tumors, as IMAX is positively correlated with microvascular density. PMID- 26806441 TI - Computer-Aided Diagnosis for Breast Ultrasound Using Computerized BI-RADS Features and Machine Learning Methods. AB - This work identifies effective computable features from the Breast Imaging Reporting and Data System (BI-RADS), to develop a computer-aided diagnosis (CAD) system for breast ultrasound. Computerized features corresponding to ultrasound BI-RADs categories were designed and tested using a database of 283 pathology proven benign and malignant lesions. Features were selected based on classification performance using a "bottom-up" approach for different machine learning methods, including decision tree, artificial neural network, random forest and support vector machine. Using 10-fold cross-validation on the database of 283 cases, the highest area under the receiver operating characteristic (ROC) curve (AUC) was 0.84 from a support vector machine with 77.7% overall accuracy; the highest overall accuracy, 78.5%, was from a random forest with the AUC 0.83. Lesion margin and orientation were optimum features common to all of the different machine learning methods. These features can be used in CAD systems to help distinguish benign from worrisome lesions. PMID- 26806442 TI - Longitudinal Transient Elastography Measurements Used in Follow-up for Patients with Cystic Fibrosis. AB - Cystic fibrosis-related liver disease (CFLD) is diagnosed using a combination of criteria. Transient elastography (TE), an ultrasonographic method to evaluate liver stiffness, can differentiate patients with and without liver disease. This retrospective study (2007-2013) aimed to detect developing CFLD using consequent TE measurements. All cystic fibrosis patients with TE measurements between 2007 and 2013 (n = 150, median age 17 (9-24) y) were included, of which 118 had a median of three (range, 2-4) measurements with an interval of 1 (1-2) y. Twenty (14%) had CFLD at the first TE measurement; five (3%) developed CFLD during follow-up. The median TE value in CFLD was 14 kPa (8.7-32.2) compared with 5.3 (4.9-5.7) in cystic fibrosis patients without liver disease (CFnoLD; p = 0.0001). In CFnoLD, TE was correlated with age (p = 0.031). A TE result >6.8 kPa had a sensitivity of 91.5% and a specificity of 91.7% in predicting CFLD, according to the receiver operating characteristics analysis. It also has a positive predictive value of 88.6% and a negative predictive value of 86.9%, increasing to 91.7% and 98%, respectively, in patients at risk (<14 y) for developing CFLD. Patients with developing CFLD had progressively increasing consecutive TE measurements. PMID- 26806443 TI - The injecting use of image and performance-enhancing drugs (IPED) in the general population: a systematic review. AB - Injecting use of image and performance-enhancing drugs (IPED) in the general population is a public health concern. A wide and varied range of IPED are now easily accessible to all through the online market. A comprehensive literature review was undertaken according to Critical Appraisal Skills Programme (CASP) guidelines for systematic review, to identify the relevant literature. No date restrictions were placed on the database search in the case of human growth hormone melanotan I and II, and oil and cosmetic injectables. In the case of anabolic androgenic steroids search dates were restricted to January 2014-2015. Publications not in English and with a lack of specificity to the topic were excluded. The review yielded 133 relevant quantitative and qualitative papers, clinical trials, clinical case presentations and editorials/reports. Findings were examined/reviewed under emergent themes which identified/measured extent of use, user profiling, sourcing, product endorsement, risk behaviours and health outcomes in users. Motivation for IPED use may be grounded in appearance, pursuit of health and youth, and body image disturbance. IPED users can practice moderated use, with pathological use linked to high-risk behaviours, which may be normalised within IPED communities. Many IPED trajectories and pathways of use are not scientifically documented. Much of this information may be available online in IPED specific discussion forums, an underutilised setting for research, where uncensored discourse takes place among users. This review underscores the need for future internet and clinical research to investigate prevalence and patterns of injecting use, and to map health outcomes in IPED users. This paper provides community-based clinical practice and health promotion services with a detailed examination and analysis of the injecting use of IPED, highlighting the patterns of this public health issue. It serves to disseminate updated publication information to health and social policy makers and those in health service practice who are involved in harm reduction intervention. PMID- 26806444 TI - Strategies to improve the fertility of fresh and frozen donkey semen. AB - Fertility rates of donkey semen in jennies are lower compared to mares. The aims of this study were to evaluate different sperm cryopreservation methods and insemination strategies to improve the fertility of donkey semen in jennies. Three experiments were performed: (1) the comparison of two freezing methods of donkey semen (conventional method and automated method); (2) the determination of a suitable insemination dose of fresh donkey semen for jennies and mares; and (3) the influence of the semen deposition site on fertility of jennies inseminated with frozen donkey semen. For experiment 1, no differences were observed in total motility, angular velocity, curvilinear velocity, straight-line velocity, and plasma membrane integrity between samples frozen with the conventional (Styrofoam box) and the automated method (TK 4000C). However, the automated method provided higher values of progressive motility and rapid cells in frozen-thawed samples in comparison with the conventional method (P < 0.05). For experiment 2, mares were bred using 500 * 10(6) fresh sperm (M); and jennies using 1 * 10(9) (J1) or 500 * 10(6) fresh sperm (J5). Pregnancy rates in M, J1, and J5 were 93% (14/15), 73% (11/15), and 40% (6/15), respectively. When using different insemination doses, 500 * 10(6) or 1 * 10(9) sperm, no significant difference was observed in pregnancy rates of mares (M, 14/15) and jennies (J1, 11/15). Furthermore, there was no significant difference between the two insemination doses in jennies. However, with an insemination dose of 500 * 10(6) fresh sperm, the pregnancy rates were significantly higher in mares (M, 14/15) than in jennies (J5, 6/15; P < 0.05). For experiment 3, the inseminations were carried out in the uterine body (UB) or in the uterine horn of jennies with frozen-thawed donkey semen. No pregnancies were achieved with inseminations performed in the UB (0/12). The pregnancy rate for uterine horn group was 28.26% (13/46) and thus significantly higher than the UB group (0%; 0/12; P < 0.05). In conclusion, the automated method showed higher values on progressive motility and rapid cells parameters compared to the conventional method and can be used as an alternative for freezing donkey semen. The increase in the number of sperm cells per insemination dose using fresh donkey semen improved the fertility rates in jennies. The deep horn inseminations using frozen-thawed donkey semen increased the pregnancy rate in jennies, and the multiple inseminations may be an option to improve the fertility rates of donkey semen in jennies. PMID- 26806445 TI - Homocysteine in embryo culture media as a predictor of pregnancy outcome in assisted reproductive technology. AB - The aim of this study was to determine whether homocysteine (hcy) concentrations in embryo culture media correlate with pregnancy outcome in assisted reproductive technology (ART) cycles. Forty patients who underwent single embryo transfer at the infertility clinic of a tertiary care center were recruited for this case control study. Spent embryo culture media from all patients were collected after single embryo transfer on day 3 (n = 40). Hcy concentrations in embryo culture media were analyzed by enzyme cycling method. Patients were grouped according to the diagnosis of a clinical pregnancy. Sixteen patients were pregnant while 24 patients failed to achieve conception. Mean Hcy levels in the culture media were significantly different between the groups (p < 0.003), as 4.58 +/- 1.31 MUmol/l in the non-pregnant group and 3.37 +/- 0.92 MUmol/l in the pregnant group. Receiver operator curve analysis for determining the diagnostic potential of Hcy for pregnancy revealed an area under the curve of 0.792 (confidence interval: 0.65-0.94; p < 0.05). A cut-off value of 3.53 MUmol/l was determined with a sensitivity of 83.3%, and a specificity of 68.8%. Lower hcy levels were associated with a better chance of pregnancy and better embryo grades. Hcy may be introduced as an individual metabolomic profiling marker for embryos. PMID- 26806446 TI - Erythema Induratum in a Patient with Pulmonary Mycobacterium avium Infection. PMID- 26806447 TI - 'Complementary & Alternative Medicine' (CAM): Ethical And Policy Issues. PMID- 26806448 TI - Pediatric Chiropractic Care: The Subluxation Question And Referral Risk. AB - Chiropractors commonly treat children for a variety of ailments by manipulating the spine to correct a 'vertebral subluxation' or a 'vertebral subluxation complex' alleged to be a cause of disease. Such treatment might begin soon after a child is born. Both major American chiropractic associations - the International Chiropractic Association and the American Chiropractic Association support chiropractic care for children, which includes subluxation correction as a treatment or preventive measure. I do not know of any credible evidence to support chiropractic subluxation theory. Any attempt to manipulate the immature, cartilaginous spine of a neonate or a small child to correct a putative chiropractic subluxation should be regarded as dangerous and unnecessary. Referral of a child to a chiropractor for such treatment should not be considered lest a bad outcome harms the child or leads to a charge of negligence or malpractice. PMID- 26806449 TI - No Understanding, No Consent: The Case Against Alternative Medicine. AB - The demand for informed consent in clinical medicine is usually justified on the basis that it promotes patient autonomy. In this article I argue that the most effective way to promote autonomy is to improve patient understanding in order to reduce the epistemic disparity between patient and medical professional. Informed consent therefore derives its moral value from its capacity to reduce inequalities of power as they derive from epistemic inequalities. So in order for a patient to have given informed consent, she must understand the treatment. I take this to mean that she has sufficient knowledge of its causal mechanisms and has accepted the explanations in which the treatment is implicated. If this interpretation of informed consent is correct, it is unethical for medical professionals to offer or endorse 'alternative medicine' treatments, for which there is no known causal mechanism, for if they do, they may end up widening the epistemic disparity. In this way, informed consent may be understood as an effective way of ruling out particular treatments in order to improve patient autonomy and maintain trust in the medical profession. PMID- 26806450 TI - Alternative Medicine and the Ethics Of Commerce. AB - Is it ethical to market complementary and alternative medicines? Complementary and alternative medicines (CAM) are medical products and services outside the mainstream of medical practice. But they are not just medicines (or supposed medicines) offered and provided for the prevention and treatment of illness. They are also products and services - things offered for sale in the marketplace. Most discussion of the ethics of CAM has focused on bioethical issues - issues having to do with therapeutic value, and the relationship between patients and those purveyors of CAM. This article aims instead to consider CAM from the perspective of commercial ethics. That is, we consider the ethics not of prescribing or administering CAM (activities most closely associated with health professionals) but the ethics of selling CAM. PMID- 26806451 TI - Moral Legitimacy: The Struggle Of Homeopathy in the NHS. AB - This article deploys a well-established theoretical model from the accountability literature to the domain of bioethics. Specifically, homeopathy is identified as a controversial industry and the strategic action of advocates to secure moral legitimacy and attract public funding is explored. The Glasgow Homeopathic Hospital (GHH) is used as the location to examine legitimizing strategies, from gaining legitimacy as a National Health Service (NHS) hospital in 1948, followed by maintaining and repairing legitimacy in response to government enquires in 2000 and 2010. An analysis of legitimizing strategies leads to the conclusion that advocates have been unsuccessful in maintaining and repairing moral legitimacy for homeopathy, thus threatening continued public funding for this unscientific medical modality. This is an encouraging development towards open and transparent NHS accountability for targeting limited public resources in pursuit of maximizing society's health and well-being. Policy implications and areas for future research are suggested. PMID- 26806453 TI - Social Media Editor: Dr. Ranjith Ramasamy. PMID- 26806454 TI - Association studies on the bovine lipoprotein lipase gene polymorphism with growth and carcass quality traits in Qinchuan cattle. AB - Lipoprotein lipase (LPL) is considered as an essential enzyme in lipid deposition and tissue metabolism. It has been proposed to be a lead candidate gene for genetic markers of lipid deposition and energy balance. In this paper, polymorphisms in the LPL gene were investigated in 554 Chinese Qinchuan cattle by PCR-RFLP and DNA sequencing. Seven single nucleotide polymorphisms (SNPs) were identified, which included one mutation (g.91C > T) in the 5'untranslated region (UTR), four synonymous mutations (g.17015A > G, g.18362G > A, g.18377T > C and g.19873T > C) and two mutations (g.25225A > G and g.25316T > G) in the 3'UTR. The frequencies of SNP g.18377T > C and g.25316T > G were skewed from Hardy-Weinberg equilibrium in all the samples (chi-square test, P < 0.05). An association analysis showed that five loci (except for g.91C > T and g.18377T > C) were significantly correlated with some growth and carcass quality traits. These results demonstrate that LPL might be a potential candidate gene for marker assisted selection (MAS). PMID- 26806455 TI - Dissecting striatal adenosine-cannabinoid receptor interactions. New clues from rats over-expressing adenosine A2A receptors. AB - This Editorial highlights a study by Chiodi et al. () showing that the effects mediated by cannabinoid CB1 receptor (CB1R) activation in the striatum are significantly reduced in rats with neuronal over-expression of adenosine A2A receptors (A2AR). Two hypotheses are derived from that study. Hypothesis A: two subpopulations of pre-synaptic CB1R in corticostriatal glutamatergic terminals exist, one forming and another not forming heteromers with A2AR. Hypothesis B: CB1R are predominantly forming heteromers with A2AR. In the case of hypothesis A, the A2AR might be required for CB1R-A2AR heteromeric signaling, whereas non heteromeric CB1R activity is inhibited by A2ARs. In the case of hypothesis B, up regulation of A2ARs may perturb heteromeric stoichiometry, thus reducing CB1R functioning. In any case, pre-synaptic striatal A2AR-CB1R heteromers emerge as important targets of the effects of cannabinoids demonstrated at the neuronal and behavioral level. Read the highlighted article 'Striatal adenosine-cannabinoid receptor interactions in rats over-expressing adenosine A2A receptors' on page 907. PMID- 26806456 TI - Plasma markers of inflammation and prediction of cardiovascular disease and mortality in African Americans with type 1 diabetes. AB - BACKGROUND: To determine whether plasma levels of markers of inflammation are predictive of the incidence of cardiovascular disease (CVD), hypertension, or mortality in African Americans with type 1 diabetes mellitus. METHODS: A total of 484 African Americans with type 1 diabetes were included. At baseline and 6-year follow-up, a clinical interview and examination were conducted to document CVD and systemic hypertension. Venous blood for glycated hemoglobin and cholesterol was obtained and albumin excretion rate measured. Mortality was assessed annually between baseline and 6-year follow-up by review of the social security death index. Baseline plasma levels of 28 inflammatory biomarkers were measured using multiplex bead analysis system. RESULTS: After adjusting for baseline age and other confounders, African Americans with type 1 diabetes in the highest quartile of plasma interferon-inducible protein 10 (IP-10) were three times more likely to develop CVD than those in the lowest quartile. African Americans with type 1 diabetes in the lowest quartiles of plasma stromal derived factor-1 (SDF-1) had a 75% higher risk of death than patients in the highest quartile, independently of age, low density lipoprotein cholesterol, body mass index, hypertension, and albuminuria. CONCLUSION: In African Americans with type 1 diabetes, high plasma IP-10 is an independent predictor for incident CVD and low SDF-1 an independent predictor for mortality. PMID- 26806457 TI - Effect of systemically increasing human full-length Klotho on glucose metabolism in db/db mice. AB - The metabolic effects of antiaging Klotho were previously investigated in vivo by genetic manipulation. We have here studied the metabolic effect of physiologic levels of circulating full length Klotho in db/db mice. Increasing the full length human Klotho levels has a positive effect on blood glucose through increasing insulin secretion. PMID- 26806460 TI - The mysterious case of the public health guideline that is (almost) entirely ignored: call for a research agenda on the causes of the extreme avoidance of physical activity in obesity. AB - Physical activity and exercise guidelines for weight management call for at least 60 min of daily activity. However, these documents fail to acknowledge that almost no obese adults meet this target and that non-adherence and dropout are even higher among obese individuals than the general population. The reasons for this level of activity avoidance among obese individuals remain poorly understood, and there are no evidence-based methods for addressing the problem. Opinions among exercise scientists are polarized. Some advocate moderate intensity and long duration, whereas others call for high intensity and shorter duration. The latter approach attributes the inactivity and high dropout to limited discretionary time and the slow accrual of visible benefits. However, higher intensity has been associated with non-adherence and dropout, whereas longer duration has not. A conceptual model is then proposed, according to which obesity interacts with intensity, causing physical activity and exercise to be associated with reduced pleasure among obese individuals. We theorize that, in turn, repeated experiences of reduced pleasure lead to avoidance. On this basis, we call for a research agenda aimed at identifying the causes of activity associated and exercise-associated displeasure in obesity and, by extension, the causes of the extreme physical inactivity among obese individuals. PMID- 26806461 TI - Microgranular acute promyelocytic leukemia presenting with leukopenia and an unusual immunophenotype. AB - The microgranular variant (M3v) of acute promyelocytic leukemia (APL) is rare, and the diagnosis can be delayed due to variability in how this condition presents. M3v blasts often have folded nuclei, but unlike traditional APL blasts, they often possess faint granules without Auer rods. In addition, microgranular APL often presents with an elevated or normal white blood cell count in contrast with the leukopenia seen in traditional APL. In APL, delayed diagnosis can lead to early death from disseminated intravascular coagulation (DIC), which is the main cause of mortality in an otherwise treatable, and often curable, leukemia. We describe a 19-year-old male with microgranular APL who presented with leukopenia and many blasts resembling non-APL AML blasts with an unexpected immunophenotypic pattern. He was treated for DIC and initiated on all-trans retinoic acid and arsenic trioxide; he achieved complete molecular remission after induction therapy. Suspicion for APL should always remain high in the presence of clinical manifestations of the disease in order that appropriate treatment can be initiated rapidly to prevent early death. PMID- 26806462 TI - Could the mosaic pattern of chromosomal abnormality predict overall survival of patients with myelodysplastic syndrome? AB - OBJECTIVE/BACKGROUND: Myelodysplastic syndromes (MDSs) are a group of monoclonal hematopoietic diseases consisting of a number of various entities. The presence of differences in chromosomal content of cells within the same individual is known as chromosomal mosaicism. The impact of mosaic pattern on the prognosis of MDS has been unclear. In this study, we aimed to determine the impact of mosaic pattern on the survival of patients with MDS. METHODS: We retrospectively evaluated 119 patients diagnosed with MDS at the Trakya University Faculty of Medicine, Department of Hematology. Giemsa-Trypsin-Giemsa banding was used to evaluate chromosomal abnormality. The effect of chromosomal abnormality mosaicism on overall survival and transformation to acute leukemia was evaluated by Kaplan Meier survival analysis. RESULTS: The mean age at diagnosis was 66.3years, and the mean disease duration was 24.2months. Chromosomal abnormality was observed in 32.5% of patients. Patients with chromosomal abnormalities comprising at least 50% metaphases had significantly lower overall survival than patients with abnormality comprising up to 50% of all abnormal metaphases (p=.003). There were no differences in transformation to acute leukemia among patients with higher and lower chromosomal mosaicism (p=.056). CONCLUSION: The most important outcome of this study was to demonstrate worse overall survival rates in MDS patients with higher abnormal chromosomal mosaicism than patients with lesser abnormal chromosomal mosaicism. Higher levels of abnormal chromosomal mosaicism did not predict transformation to acute leukemia. The cause of worse outcomes of patients with higher abnormal chromosomal mosaicism may be related to clonal mass. PMID- 26806464 TI - Evaluating the sensitivity, reproducibility and flexibility of a method to test hard shell capsules intended for use in dry powder inhalers. AB - Pharmaceutical tests for hard shell capsules are designed for orally administered capsules. The use of capsules in dry powder inhalers is widespread and increasing and therefore more appropriate tests are required to ensure quality and determine if these capsules are fit for purpose. This study aims to determine the flexibility, reproducibility and sensitivity of a quantitative method that is designed to evaluate the puncture characteristics of different capsule shell formulations under different climatic conditions. A puncture testing method was used to generate force displacement curves for five capsule formulations that were stored and tested at two different temperatures (5 degrees C and 19 degrees C). Force-displacement puncture profiles were reproducible for individual capsule shell formulations. The methodology was able to discriminate between capsules produced using different primary materials i.e. gelatin versus hypromellose, as well as more minor changes to capsule formulation i.e. different material grades and excipients. Reduced temperature increased the forces required for capsule puncture however further work is required to confirm its significance. Results indicate the method provides a reproducible and sensitive means of evaluating capsule puncture. Future studies should validate the methodology at different test sites, using different operators and with different capsule shell formulations. PMID- 26806463 TI - Essential proteins and possible therapeutic targets of Wolbachia endosymbiont and development of FiloBase--a comprehensive drug target database for Lymphatic filariasis. AB - Lymphatic filariasis (Lf) is one of the oldest and most debilitating tropical diseases. Millions of people are suffering from this prevalent disease. It is estimated to infect over 120 million people in at least 80 nations of the world through the tropical and subtropical regions. More than one billion people are in danger of getting affected with this life-threatening disease. Several studies were suggested its emerging limitations and resistance towards the available drugs and therapeutic targets for Lf. Therefore, better medicine and drug targets are in demand. We took an initiative to identify the essential proteins of Wolbachia endosymbiont of Brugia malayi, which are indispensable for their survival and non-homologous to human host proteins. In this current study, we have used proteome subtractive approach to screen the possible therapeutic targets for wBm. In addition, numerous literatures were mined in the hunt for potential drug targets, drugs, epitopes, crystal structures, and expressed sequence tag (EST) sequences for filarial causing nematodes. Data obtained from our study were presented in a user friendly database named FiloBase. We hope that information stored in this database may be used for further research and drug development process against filariasis. URL: http://filobase.bicpu.edu.in. PMID- 26806465 TI - AN in vitro evaluation of a carmustine-loaded Nano-co-Plex for potential magnetic targeted intranasal delivery to the brain. AB - Targeted delivery of carmustine (BCNU), an efficient brain tumor therapeutic, has been challenged with bioavailability issues due to the Blood Brain Barrier (BBB). The currently effective delivery approach is by implants at the site of the tumor, but this is highly invasive. The intranasal route, which is non-invasive and bypasses the BBB, may be alternative route for delivering BCNU to the brain. In this work, polyvinyl alcohol/polyethyleneimine/fIuorecein isothiocyanate complex (Polyplex) coated iron-oxide nanoparticles (Magnetite) were synthesized employing co-precipitation, epoxidation and EDC/NHS coupling reactions. The Polyplex coated magnetite (Nano-co-Plex) was loaded with BCNU for potential magnetically targeted delivery to the brain following intranasal administration. The Nano-co-Plex was characterized employing Thermogravimetric analysis (TGA), Superconducting Quantum Interference Device (SQUID) magnetometry, Fourier Transform Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR), X-ray Diffractometry (XRD), Transmission Electron Microscopy (TEM) and Zetasize analysis. Results revealed superparamagnetic hexagonally shaped "core-shell" nanoparticles with cell labeling attributes, of size ranging between 30-50 nm, and a zeta potential value of + 32 +/- 2 mV. The Nano-co-Plex synthesized was found to possess high degree of crystallinity with 32% Polyplex coating. The loading and release studies indicated a time-dependent loading with maximum loading capacity of 176.82 MUg BCNU/mg of the carrier and maximum release of 75.8% of the loaded BCNU. Cytotoxicity of the BCNU-loaded Nano-co-Plex displayed superiority over the conventional BCNU towards human glioblastoma (HG) cells. Cell studies revealed enhanced uptake and internalization of BCNU-loaded Nano-co plex in HG cells in the presence of an external magnetic field. These Nano-co Plexes may be ideal as an intranasal magnetic drug targeting device for BCNU delivery. PMID- 26806466 TI - An elastic liposomal formulation for RNAi-based topical treatment of skin disorders: Proof-of-concept in the treatment of psoriasis. AB - RNA interference (RNAi) is a rapidly emerging approach for targeted gene silencing to alleviate disease pathology. However, lack of efficient carriers for targeted delivery delays the clinical translation of RNAi. An interesting target for local RNAi therapeutics is the skin as it allows direct access to target cells. Still, applications are limited due to the effective skin barrier which hinders penetration. Herein, a description is given of a liposomal carrier, called 'DDC642', capable of delivering RNAi molecules to the epidermis of impaired and intact human skin, without targeting the dermis or circulatory system. In a psoriasis tissue model, down-regulation of the psoriasis marker human beta-defensin 2 by DDC642-delivered siRNA was confirmed, providing proof-of concept. These liposomes thus hold great potential as topical delivery system for RNAi therapeutics in the treatment of numerous skin diseases. PMID- 26806467 TI - Effect of the product type, of the amount of applied sunscreen product and the level of protection in the UVB range on the level of protection achieved in the UVA range. AB - Using a topical product is part of the overall strategy for skin cancer prevention. The level of protection attainable when using commercial products is indicated by the Sun Protection Factor (SPF) value, in use everywhere. This value reflects the level of protection primarily in the UVB range. However, UVA radiation also has deleterious effects on the skin, and it is essential to prevent it, which is why products must offer a wide spectrum of protection. Tests conducted in vivo, before any marketing, are done by applying the studied product at a rate of 2.0 mg cm(-2), while users, in practice, only use 1.0-1.5 mg cm(-2). We now know that this reduction in the amount of applied product greatly affects the SPF. To complete the state of knowledge in this area, we sought to evaluate the effect of a decrease in the amount of applied sunscreen product by studying sunscreen creams and oils on the level of protection attainable in the UVA range. We have shown that the PF-UVA is divided by a factor of 2.2, on average, when the amount of applied product is reduced by half, with differences depending on the product type under consideration (cream or oil) and depending on the SPF of the preparation. PMID- 26806468 TI - Use of a Dedicated, Non-Physician-led Mental Health Team to Reduce Pediatric Emergency Department Lengths of Stay. AB - OBJECTIVES: Utilization of emergency departments (EDs) for pediatric mental health (MH) complaints is increasing. These patients require more resources and have higher admission rates than those with nonpsychiatric complaints. METHODS: A multistage, multidisciplinary process to reduce length of stay (LOS) and improve the quality of care for patients with psychiatric complaints was performed at a tertiary care children's hospital's ED using Lean methodology. This process resulted in the implementation of a dedicated MH team, led by either a social worker or a psychiatric nurse, to evaluate patients, facilitate admissions, and arrange discharge planning. We conducted a retrospective, before-and-after study analyzing data 1 year before through 1 year after new process implementation (March 28, 2011). Our primary outcome was mean ED LOS. RESULTS: After process implementation there was a statistically significant decrease in mean ED LOS (332 minutes vs. 244 minutes, p < 0.001). An x-bar chart of mean LOS shows special cause variation. Significant decreases were seen in median ED LOS (225 minutes vs. 204 minutes, p = 0.001), security physical interventions (2.0% vs. 0.4%, p = 0.004), and restraint use (1.7% vs. 0.1%, p < 0.001). No significant change was observed in admission rate, 72-hour return rate, or patient elopement/agitation events. Staff surveys showed improved perception of patient satisfaction, process efficacy, and patient safety. CONCLUSIONS: Use of quality improvement methodology led to a redesign that was associated with a significant reduction in mean LOS of patients with psychiatric complaints and improved ED staff perception of care. PMID- 26806469 TI - Phosphorescent columnar hybrid materials containing polyionic inorganic nanoclusters. AB - The ternary polyionic inorganic compound Cs2Mo6Br14 and 18-crown-6 ethers bearing two o-terphenyl units have been combined to design phosphorescent columnar liquid crystalline hybrid materials. The obtained host-guest complexes are very stable even at high temperatures. Depending on their surrounding atmosphere, these hybrids switch reversibly from a high-to-low luminescence state and show a very stable emission intensity up to 140 degrees C. PMID- 26806471 TI - Extensive juvenile "babysitting" facilitates later adult maternal responsiveness, decreases anxiety, and increases dorsal raphe tryptophan hydroxylase-2 expression in female laboratory rats. AB - Pregnancy and parturition can dramatically affect female neurobiology and behavior. This is especially true for laboratory-reared rodents, in part, because such rearing prevents a host of developmental experiences that females might undergo in nature, including juvenile alloparenting. We examined the effect of chronic exposure to pups during post-weaning juvenile life (days 22-36) on adult maternal responsiveness, anxiety-related behaviors, and dorsal raphe tryptophan hydroxylase-2 (TPH2) and serotonin transporter (SERT) levels in nulliparous rats. Adult females with juvenile alloparental experience showed significantly faster sensitized maternal responsiveness, less anxiety, and more dorsal raphe TPH2. Juvenile alloparenting did not affect females' later social novelty and preference behaviors toward adults, suggesting their increased interest in pups did not extend to all social partners. In a second experiment, suckling a pregnant dam (achieved by postpartum estrus reinsemination), interacting with her after standard laboratory weaning age, and a 3-day exposure to younger siblings also reduced juvenile females' later anxiety but did not affect maternal responsiveness or TPH2. Thus, extensive juvenile "babysitting" can have long-term effects reminiscent of pregnancy and parturition on maternal responsiveness and anxiety, and these effects may be driven by upregulated serotonin. (c) 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 492-508, 2016. PMID- 26806472 TI - Cooperative Reductive Elimination: The Missing Piece in the Oxidative-Coupling Mechanistic Puzzle. AB - The reaction between benzoic acid and methylphenylacetylene to form an isocoumarin is catalyzed by Cp*Rh(OAc)2 in the presence of Cu(OAc)2 (H2 O) as an oxidant and a leading example of oxidative-coupling reactions. Its mechanism was elucidated by DFT calculations with the B97D functional. The conventional mechanism, with separate reductive-elimination and reoxidation steps, was found to yield a naphthalene derivative as the major product by CO2 extrusion, contradicting experimental observations. The experimental result was reproduced by an alternative mechanism with a lower barrier: In this case, the copper acetate oxidant plays a key role in the reductive-elimination step, which takes place through a transition state containing both rhodium and copper centers. This cooperative reductive-elimination step would not be accessible with a generic oxidant, which, again, is in agreement with available experimental data. PMID- 26806473 TI - Plasma Vasoprotective Eicosanoid Concentrations in Healthy Greyhounds and Non Greyhound Dogs. AB - BACKGROUND: Hypertension and albuminuria often coexist in Greyhounds, suggesting generalized vascular dysfunction that could contribute to the development of a variety of diseases in this breed. Eicosanoid metabolites of arachidonic acid (AA) mediate endothelial function, vascular reactivity, and proteinuria in humans and in rodent models. HYPOTHESIS: The eicosanoid profile of Greyhounds is shifted toward metabolites that promote vascular dysfunction, hypertension, and proteinuria. ANIMALS: Healthy Greyhounds (n = 20) and non-Greyhound (n = 20) dogs that were consecutively enrolled in a blood donor program. METHODS: Prospective study. Plasma eicosanoid metabolites were assayed by liquid chromatography/electrospray ionization mass spectrometry (LC/ESI/MS) and compared to systolic blood pressure (SP) measurements and urine albumin concentration. RESULTS: Isomers of hydroxyeicosatetraenoic acid (HETE) were higher in Greyhounds than non-Greyhounds (median, range in pmol/mL: 5(S)HETE 19.82, 8.55-32.95 versus 13.54, 4.33-26.27, P = .033; 8(S)HETE 9.39, 3.28-19.84 versus 5.80, 2.25-17.66, P = .002; 9(S)HETE 9.46, 2.43-13.79 versus 5.82, 1.50-17.16, P = .026; 12(S)HETE 10.17, 3.81-40.06 versus 7.24, 2.9-16.16, P = .022). Dihydroxyeicosatrienoic acid (DHET) isomers also were higher in Greyhounds compared to non-Greyhounds (mean +/ SD in pmol/mL: 8,9DHET 5.78 +/- 2.13 versus 4.03 +/- 1.36, P = .004; 11,12DHET 11.98 +/- 2.86 versus 8.90 +/- 3.48, P = .004; 14,15DHET 7.23 +/- 2.19 versus 5.76 +/- 1.87, P = .028). Albuminuria correlated with total DHET (rs = 0.46, P = .003). SP was positively correlated with 11,12EET (rs = 0.42, P = .006) and 20(S)HETE (rs = 0.38, P = .017). SP and 8,9EET were inversely correlated (rs = 0.49, P = .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma eicosanoid profile in Greyhounds was consistent with activation of metabolic pathways known to promote vascular dysfunction and might contribute to higher blood pressures and albuminuria. Inhibition of these eicosanoid pathways should be evaluated as therapeutic targets in Greyhounds. PMID- 26806475 TI - The perils of the body count. PMID- 26806474 TI - The American College of Rheumatology Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis. AB - OBJECTIVE: Early diffuse cutaneous systemic sclerosis (dcSSc) is characterized by rapid changes in the skin and internal organs. The objective of this study was to develop a composite response index in dcSSc (CRISS) for use in randomized controlled trials (RCTs). METHODS: We developed 150 paper patient profiles with standardized clinical outcome elements (core set items) using patients with dcSSc. Forty scleroderma experts rated 20 patient profiles each and assessed whether each patient had improved or not improved over a period of 1 year. Using the profiles for which raters had reached a consensus on whether the patients were improved versus not improved (79% of the profiles examined), we fit logistic regression models in which the binary outcome referred to whether the patient was improved or not, and the changes in the core set items from baseline to followup were entered as covariates. We tested the final index in a previously completed RCT. RESULTS: Sixteen of 31 core items were included in the patient profiles after a consensus meeting and review of test characteristics of patient-level data. In the logistic regression model in which the included core set items were change over 1 year in the modified Rodnan skin thickness score, the forced vital capacity, the patient and physician global assessments, and the Health Assessment Questionnaire disability index, sensitivity was 0.982 (95% confidence interval 0.982-0.983) and specificity was 0.931 (95% confidence interval 0.930-0.932), and the model with these 5 items had the highest face validity. Subjects with a significant worsening of renal or cardiopulmonary involvement were classified as not improved, regardless of improvements in other core items. With use of the index, the effect of methotrexate could be differentiated from the effect of placebo in a 1-year RCT (P = 0.02). CONCLUSION: We have developed a CRISS that is appropriate for use as an outcome assessment in RCTs of early dcSSc. PMID- 26806476 TI - The present day potential role of fractional flow reserve-guided coronary artery bypass graft surgery. AB - The favorable impact of fractional flow reserve measurements on the decision making and overall outcomes of percutaneous coronary artery intervention is well established. However, the clinical application of fractional flow reserve in surgical revascularizations is still debated. The purpose of this article is to provide a comprehensive review on the current potential role of fractional flow reserve guidance in coronary artery bypass grafting. PMID- 26806477 TI - Preoperative PFTs: The answer is blowing in the wind. PMID- 26806478 TI - Hypoplastic left heart syndrome: What's next? PMID- 26806479 TI - Why women bypass front-line health facility services in pursuit of obstetric care provided elsewhere: a case study in three rural districts of Tanzania. AB - OBJECTIVES: In the Tanzanian health system, women are expected to first visit their nearest front-line health facility (FLF) for delivery. However, women frequently bypass these FLF. Our study estimates the extent of bypassing for childbirth and assesses factors associated with this behaviour. METHODS: Data describing the experiences of 597 women who recently delivered at a facility and the EmONC service capability at 107 health facilities were collected in 2011. Women who did not deliver at their nearest FLF were considered 'bypassers'. Factors associated with bypassing were assessed using multivariate logistic regression models. Three sets of analyses were conducted: among 597 women who delivered at the first facility they visited, among 521 women with no previous complications, and among 407 women not primigravida and without previous complications. RESULTS: More than 75.4% of women bypassed. In the fully adjusted model of all 597 women those who had experienced complications were more likely to bypass for delivery [OR = 6.31 (2.36, 16.86)]. In the fully adjusted model excluding women with previous complications, primigravida women were more likely to bypass [OR = 3.70 (1.71, 8.01)]. Fully adjusted models for each set of analysis found that, for each additional emergency obstetric and newborn care signal function (EmONC SF) available at the nearest FLF, women's odds of bypassing almost halved. CONCLUSIONS: Bypassing is highly associated with EmONC SF score at nearest FLF, controlling for individual and community-level factors. PMID- 26806480 TI - Immune memory: ILC2s drive allergen recall. PMID- 26806481 TI - Mucosal immunology: Neuroendocrine cells regulate lung inflammation. PMID- 26806482 TI - Immune memory: Lingering human T cells. PMID- 26806483 TI - The bigger B cell picture. PMID- 26806485 TI - T cell signalling: TCR takedown in TH2 cells. PMID- 26806484 TI - Natural killer cell memory in infection, inflammation and cancer. AB - Immunological memory can be defined as a quantitatively and qualitatively enhanced immune response upon rechallenge. For natural killer (NK) cells, two main types of memory exist. First, similarly to T cells and B cells, NK cells can exert immunological memory after encounters with stimuli such as haptens or viruses, resulting in the generation of antigen-specific memory NK cells. Second, NK cells can remember inflammatory cytokine milieus that imprint long-lasting non antigen-specific NK cell effector function. The basic concepts derived from studying NK cell memory provide new insights about innate immunity and could lead to novel strategies to improve treatments for infectious diseases and cancer. PMID- 26806486 TI - Immune memory: Sequential evolution of B cell memory. PMID- 26806487 TI - Complete genome sequence of Klebsiella pneumoniae J1, a protein-based microbial flocculant-producing bacterium. AB - Klebsiella pneumoniae J1 is a Gram-negative strain, which belongs to a protein based microbial flocculant-producing bacterium. However, little genetic information is known about this species. Here we carried out a whole-genome sequence analysis of this strain and report the complete genome sequence of this organism and its genetic basis for carbohydrate metabolism, capsule biosynthesis and transport system. PMID- 26806488 TI - Complete genome sequence of strain Lentibacillus amyloliquefaciens LAM0015(T) isolated from saline sediment. AB - The type strain Lentibacillus amyloliquefaciens LAM0015(T) with considerably highly NaCl tolerance is a member of halophiles. Here we report its genome sequence, the first to publish complete genome sequence of the Lentibacillus genus. It contains 3,858,520bp with an average GC content of 42.12%, encoding multiple valuable proteins academically and industrially. The genome sequence of strain LAM0015(T) provides basic information for further elucidation of halophilic mechanism and wider exploitation of functional genes. PMID- 26806489 TI - Complete genome sequence of Arthrobacter alpinus ERGS4:06, a yellow pigmented bacterium tolerant to cold and radiations isolated from Sikkim Himalaya. AB - Arthrobacter alpinus ERGS4:06, a yellow pigmented bacterium which exhibited tolerance to cold and UV radiations was isolated from the glacial stream of East Rathong glacier in Sikkim Himalaya. Here we report the 4.3Mb complete genome assembly that has provided the basis for potential role of pigments as a survival strategy to combat stressed environment of cold and high UV-radiation and additionally the ability to produce cold active industrial enzymes. PMID- 26806490 TI - Improvement of in vitro stability and pharmacokinetics of hIFN-alpha by fusing the carboxyl-terminal peptide of hCG beta-subunit. AB - Improving in vivo half-life and in vitro stability of protein-based therapeutics is a current challenge for the biopharmaceutical industry. In particular, recombinant human interferon alpha-2b (rhIFN-alpha2b), which belongs to a group of cytokines extensively used for the treatment of viral diseases and cancers, shows a poor stability in solution and an extremely short plasma half-life which determines a strict therapeutic regimen comprising high and repeated doses. In this work, we have used a strategy based on the fusion of the carboxyl-terminal peptide (CTP) of human chorionic gonadotropin (hCG) beta-subunit, bearing four O linked oligosaccharide recognition sites, to each or both N- and C-terminal ends of rhIFN-alpha2b. Molecules containing from 5 (CTP-IFN and IFN-CTP) to 9 (CTP-IFN CTP) O-glycosylation sites were efficiently expressed and secreted to CHO cells supernatants, and exhibited antiviral and antiproliferative bioactivities in vitro. Significant improvements in pharmacokinetics in rats were achieved through this approach, since the doubly CTP-modified IFN variant showed a 10-fold longer elimination half-life and a 19-fold decreased plasma apparent clearance compared to the wild-type cytokine. Moreover, CTP-IFN-CTP demonstrated a significant increase in in vitro thermal resistance and a higher stability against plasma protease inactivation, both features attributed to the stabilizing effects of the O-glycans provided by the CTP moiety. These results constitute the first report that postulates CTP as a tag for improving both the in vitro and in vivo stability of rhIFN-alpha2b which, in turn, would positively influence its in vivo bioactivity. PMID- 26806491 TI - Quantum algorithms for topological and geometric analysis of data. AB - Extracting useful information from large data sets can be a daunting task. Topological methods for analysing data sets provide a powerful technique for extracting such information. Persistent homology is a sophisticated tool for identifying topological features and for determining how such features persist as the data is viewed at different scales. Here we present quantum machine learning algorithms for calculating Betti numbers--the numbers of connected components, holes and voids--in persistent homology, and for finding eigenvectors and eigenvalues of the combinatorial Laplacian. The algorithms provide an exponential speed-up over the best currently known classical algorithms for topological data analysis. PMID- 26806492 TI - New insights: A role for O-GlcNAcylation in diabetic complications. AB - Diabetes is a debilitating metabolic disease that is riddled with complications that can cause blindness, renal failure, nerve damage, and cardiovascular disease. Poor glycemic control is thought to be a key initiator in the progression of diabetic complications. Hyperglycemia has been shown to increase flux through the hexosamine biosynthetic pathway (HBP) to initiate many of the toxic effects of glucose. The major endpoint of the HBP is the formation of uridine diphosphate beta-D-N-acetylglucosamine (UDP-GlcNAc), the donor for protein O-GlcNAcylation, and complex extracellular glycosylation. O-GlcNAcylation is a dynamic nutrient sensitive post-translational modification that is characterized by the addition of single beta-D-N-acetylglucosamine to the serine and/or threonine residues of almost every functional class of protein. O-GlcNAc is extremely abundant and cycles on and off proteins by the concerted action of a transferase and a hydrolase. O-GlcNAc serves as a nutrient/stress sensor regulating several processes, such as signaling, transcription, cytoskeletal dynamics, and cell division. Altered O-GlcNAc signaling is directly involved in the pathogenesis of diabetes and new insights are revealing the importance of O GlcNAc in diabetic complications. The goal of this review is to summarize O GlcNAcylation, to present the current evidence for the role of O-GlcNAc in diabetic complications, and discuss conclusions and future directions for research on O-GlcNAc in the progression of diabetic complications. PMID- 26806493 TI - Mixed Micelles for Targeted and Efficient Doxorubicin Delivery to Multidrug Resistant Breast Cancer Cells. AB - For efficient treatment of multidrug-resistance (MDR) breast cancer cells, design of biocompatible mixed micelles with diverse functional moieties and superior stability is needed for targeted delivery of chemical drugs. In this study, polypropylene glycol (PPG)-grafted hyaluronic acid (HA) copolymers (PPG-g-HA) are used to make mixed micelles with different amounts of pluronic L61, named PPG-g HA/L61 micelles. Optimized PPG-g-HA/L61 micelles with 3% pluronic L61 exhibit great stability in aqueous solution, superior biocompatibility, and significantly increased uptake into MCF-7 MDR cells via HA-CD44-specific interactions when compared to free doxorubicin (DOX) and other types of micelles. In addition, DOX in PPG-g-HA/L61 micelles with 3% pluronic L61 have toxicity in MCF-7 MDR cells but significantly lower toxicity in fibroblast L929 cells compared to free DOX. Thus, PPG-g-HA/L61 micelles with 3% pluronic L61 content can be a promising nanocarrier to overcome MDR and release DOX in a hyaluronidase-sensitive manner without any toxicity to normal cells. PMID- 26806494 TI - [Regional registry of pulmonary embolism]. AB - INTRODUCTION: Pulmonary embolism (PE) together with coronary heart disease and arterial hypertension are most common diseases of cardiovascular system. Due to its high mortality rate it is worth of attention. AIM: to describe characteristics of patients with PE, provide data about treatment and inpatient mortality rate. Also to identify an occurence of right-sided heart thrombi in patients with PE and efficiency/safety of thrombolytic therapy in this subpopulation. To evaluate effectiveness/importance of basic oncology screening in patients with PE (meaning efficiency of provided examinations to uncover hidden malignancy). METHODS: Our registry is based on observation of consecutive patients with PE hospitalized in our hospital (catchment area of Znojmo region, 130,000 inhabitants) since July 2011 until April 2014. We collected data about 188 patients diagnosed with acute or subacute PE by perfusion lung scan, CT angiography or typical symptoms with echocardiography findings. RESULTS: In the cohort there were 71 men (37.8%) and 117 women (62.2%), average age 66 years (16 94), 72.9% of patients were older than 60 years of age. History of thromboembolic disease was present in 37 patients (19.7%), malignancy in 36 of them (19.1%), signs of deep vein thrombosis in 36 patients (19.1%), hereditary thrombophilia in 11 (5.9%), recent injury with immobilisation in 10 (5.3%), recent surgery in 14 patients (7.4%) and atrial fibrillation in 22 patients (11.7%). Right heart thrombi were found in 3 patients (1.6%) out of 176 who were examined. Hospital mortality rate reached 5.6%, 3 months mortality rate was 9.4% (data collected from 85.1% of all patients) and 1 year mortality rate was 19.1% (data from 61.2% of all patients). An occult cancer was diagnosed during hospital stay only in 3 patients (1.6%), another 6 malignancies manifested themselves after longer period of time. Median length of hospital stay was 7 days. Thrombolysis was used in 14 patients (7.4%). Bleeding complications of anticoagulant or thrombolytic therapy occured in 4 patients (2.1%) during hospital care--epistaxis, severe haematoma of extremities with necessity of surgical treatment and haematemesis in 2 patients. Cerebral hemorrhage was not present in our cohort of patients. CONCLUSION: PE isnt rare condition, we can encounter it in various medical fields, but due to its diversity of symptoms and unclear prognosis, it continues to be serious clinical problem. Hospital mortality rate is higher in patients with PE than in those with acute coronary syndrome, which is in accordance with published data. Detection of right-sided heart thrombi is about half of that described in literature. Prevalence of dyspnoe and chest pain are consistent with reported data, but occurence of syncope and hemoptysis in our registry is far less common. Screening of occult cancer could be more effective. The therapy seems to be safe, a life threatening bleeding was not present even when thrombolysis was used. PMID- 26806495 TI - [Antithrombotic therapy and nonvariceal upper gastrointestinal bleeding]. AB - BACKGROUND: The incidence of acute upper gastrointestinal bleeding is about 85 108/100,000 inhabitants per year, nonvariceal bleeding accounts for 80-90%. Antiplatelet and anticoagulation treatment are the significant risk factors for upper gastrointestinal bleeding. OBJECTIVES: To evaluate the occurrence of upper gastrointestinal bleeding in the general community of patients in a county hospital. And to compare the role played by antiplatelet and anticoagulation drugs and other risk medication. DESIGN AND METHODS: Retrospective analysis of patients over 18 years of age who underwent endoscopy for acute upper gastrointestinal bleeding or anaemia (haemoglobin<100 g/l) with proved source of blood losses in upper gastrointestinal tract during a hospital stay in 2013 (from January to June). RESULTS: We included 111 patients of average age 69+/-15 years, men 60%. Nonvariceal bleeding accounted for 90% of the cases. None of the patients with variceal bleeding (10% of patients) took antiplatelet or anticoagulation therapy. There were 100 patients with nonvariceal bleeding of average age 70+/-15, 61% men. With the symptoms of acute bleeding (hematemesis, melena) presented in 73% of patients. The most frequent cause of bleeding was gastric and duodenal ulcer (54%). 32% of patients with nonvariceal bleeding had antiplatelets, 19% anticoagulants and 10% used nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors or corticosteroids. 30-days mortality of patients with nonvariceal bleeding was 11%, annual mortality was 23%. There was no significant difference in mortality, blood transfusion requirements or surgical intervention between the patients with antithrombotic agents and without them. 25% of patients (8 patients) using acetylsalicylic acid did not fulfil the indication for this treatment. CONCLUSION: Among the patients examined by endoscopy for symptomatic nonvariceal bleeding and/or anaemia (haemoglobin<100 g/l) significantly higher portions of patients are taking antiplatelet rather than anticoagulation therapy. This may be caused by greater use of these drugs in the population, but on the other hand it may reflect an association with greater risk of gastrointestinal bleeding. With regard to that, it is alarming, that there still exists a nonnegligible percentage of patients taking acetylsalicylic acid even though they do not meet the indication for the prescription according to the guidelines. PMID- 26806496 TI - [Ventilatory function in patients with silicosis or coal workers' pneumoconiosis]. AB - OBJECTIVES: The aim of the study was to determine ventilatory function in a group of patients with silicosis and coal workers pneumoconisos (CWP) newly granted as occupational disease. METHODS: The authors have undertaken the analysis of all cases of occupational silicosis and CWP which were diagnosed in men in the South Moravia region. Information on ventilatory function, chest symptoms, age, working and smoking history was collected during the medical surveys, including spirometry testing and chest radiography. Diagnosis was based on history of occupational exposure to coal or silica dust, chest x-ray findings, using International Labour Office classification. RESULTS: In the years 1997-2014, 116 occupational silicosis and coal workers' pneumoconiosis have been notified. There were diagnosed 42 cases of simple and 17 cases of complicated silicosis, 40 cases of the simple and 17 cases of complicated CWP. Duration of exposure to respiratory hazards, smoking history and prevalence of ventilatory impairment were not significantly different between these groups. The mean age of persons at diagnosing occupational disease was 61.0 (SD 11.2) years, the mean duration of exposure to respirable dust was 24.7 (SD 10.2) years. Abnormal spirometry results were detected in 51.7% of pneumoconiotics--8.6% with restrictive, 11.2% with obstructive, and 31.9 with mixed impairment. The prevalence of ventilatory function impairment was found to be significantly associated with chronic obstructive pulmonary disease and age. CONCLUSIONS: Testing of ventilatory function has an important role in the evaluation of lung disease in employees exposed to various respirable hazards. Although such testing was not useful for diagnosing silicosis or CWP, it was important for evaluating compensation amount for occupational disease in 51.7% pneumoconiotic patiens. PMID- 26806497 TI - [Lenalidomide treatment in myelodysplastic syndrome with 5q deletion--Czech MDS group experience]. AB - Myelodysplastic syndrome (MDS) is a common hematological disease in patients over sixty. Despite intensive research, the therapy of this heterogeneous blood disease is complicated. In recent years, two new therapeutic approaches have been proposed: immunomodulation and demethylation therapy. Immunomodulation therapy with lenalidomide represents a meaningful advance in the treatment of anemic patients, specifically those with 5q- aberrations. As much as 60-70% of patients respond and achieve transfusion independence. We present the initial lenalidomide experience of the Czech MDS group. We analyze Czech MDS register data of 34 (31 female; 3 male; median age 69 years) chronically transfused low risk MDS patients with 5q- aberration treated by lenalidomide. Twenty-seven (79.4%) patients were diagnosed with 5q- syndrome, 5 patients with refractory anemia with multilineage dysplasia, 1 patient with refractory anemia with excess of blasts 1, and 1 patient with myelodysplastic/myeloproliferative unclassified. Response, as represented by achieving complete transfusion independence, was achieved in 91% of patients. A true 5q- syndrome diagnosis in most our patients may be responsible for such a high response rate. Complete cytogenetic response was reached in 15% of patients and partial cytogenetic response in 67%, within a median time of 12 months. TP53 mutation was detected in 15% (3 from 18 tested) and 2 of these patients progressed to higher grade MDS. The majority of patients tolerated lenalidomide very well. Based on this albeit small study, we present our findings of high lenalidomide efficacy as well as the basic principles and problems of lenalidomide therapy. PMID- 26806498 TI - [Investigation of tubular reabsorption of phosphates in patients with chronic kidney disease]. AB - INTRODUCTION: Moderate to medium decrease in glomerular filtration (GFR) in individuals with chronic kidney disease (CKD) does not need to be associated with hyperphosphatemia due to an adaptive decrease in tubular reabsorption of phosphates (TRPi) in residual nephrons. The clinical assessment of this function is performed based on the measurement of fractional phosphate excretion (FEPi), which is a quantity specifying the proportion of the filtered amount of phosphates which is excreted in the urine. This quantity may provide useful information about the involvement of kidneys in phosphate homeostasis of the internal environment. This study focuses on the comparison of a kr(FEPi) value examined based on a ratio of a phosphate clearance (CPi) and a creatinine clearance (CKr) marked kr(FEPi), and a value calculated based on a ratio of CPi and an exactly measured GFR as an inulin clearance (Cin), marked as in(FEPi).The goal of comparing the two methods of examining FEPi was to establish to what extent it is possible to evaluate the degree of inhibition of tubular phosphate transport in residual nephrons based on a simple examination of kr(FEPi) . METHODOLOGY: The examination of in(FEPi) and kr(FEPi) was carried out for 53 patients with CKD. The values of the examined quantities were as follows: SKr 199+/-45 umol/l; SPi 1.41+/-0.29 mmol/l; CKr 0,95+/-0.36 ml/s/1.73 m2; Cin 0.71+/ 0.25 ml/s/1.73 m2. For the purpose of comparison a cohort of 18 healthy volunteers was examined. RESULTS: For individuals with CKD an average value of kr(FEPi) equalled 29.1+/-10.9% and in(FEPi) 52.4+/-4.3%. The values of in(FEPi) were higher than kr(FEPi) (p<0.001) for all patients, although an average CPi value for patients with CKD did not significantly differ from the control cohort (0.22 vs 0.21 ml/s/1.73 m2). The values of in(FEPi) increased proportionally to SKr values and at higher values SKr (>300 umol/l) they gradually approached 100% (indicating the complete inhibition of tubular reabsorption of phosphates in residual nephrons). The values of in(FEPi) were higher in all patients with CKD than kr(FEPi) as expected, likely because the value CKr decreases at a slower rate than Cin (GFR) in individuals with CKD as a result of increased tubular secretion of creatinine in residual nephrons. CONCLUSION: The results of this study support the assumption that, provided the values of kr(FEPi) which are easily measurable in clinical practice have reached 50-60%, almost complete inhibition of tubular reabsorption of phosphates in residual nephrons must be assumed and no favourable effect of phosphatonins on renal phosphate excretion can be expected. When looking for new possibilities of inhibition of tubular phosphate reabsorption, potential adverse effects of phosphatonins on organs must be considered. PMID- 26806499 TI - [Role of soluble receptor ST2 measurment in diagnosis and prognostic stratification in patients with heart failure]. AB - ST2 is a member of the interleukin 1 (IL1) receptor family and consists of a trans-membrane ligand (STL2) and a soluble form (sST2). sST2 is released from cardiomyocytes and fibroblasts after mechanical strain and has been identified as a novel biomarker of cardiac stress, fibrosis and remodelling. Many studies showed that sST2 brings important prognostic information in patients with heart failure. Elevated sST2 concentrations predicted risk of hospitalization and mortality independently on natriuretic peptides levels and on other clinical variables. Some stu-dies showed diagnostic role of sST2 u patients with heart failure and normal ejection fraction. PMID- 26806500 TI - [Geriatric multimorbidity--one of the key problem of contemporary medicine]. AB - In the elderly population there are common permanent decrease of functional capacity, gradual emergence of various diseases leading to the wider multimorbidity and increased problems in the social sphere, which can develop frailty and social dependency. The paper analyzes the complex issue of geriatric multimorbidity and emphasizes its pitfalls, the need of an interdisciplinary approach and thinking of doctors, including the risks of modern pharmacotherapy. The aim of geriatric medicine is to optimize residual functions despite the decline in total functional capacity with increasing multimorbidity. The authors want to direct the attention of the professional community to the permanently growing numbers of the elderly and to emphasize the need of awareness of the problem so that they could understand and cope with this absolutely new reality. PMID- 26806501 TI - [Carotid stenosis--diagnosis and treatment]. AB - Diagnosis and treatment of carotid stenosis is under incessant development. Especially in last years, we have noticed significant changes in opinions based on the results of meta-analyses of old evidence and the new evidence as well. Important factor involved is the fast development of new endovascular therapies. In reaction to these changes, several medical societies published their guidelines for the management of carotid stenosis. Even though, all of them are based practically on the same published medical evidence, they are not always similar in recommendations. The aim of our work was to summarize actual recommendations regarding management of carotid stenosis. The management of asymptomatic and symptomatic patients is being discussed separately where appropriate because these two groups of patients are very different. The recommendations for selection of type of intervention between carotid endarterectomy and carotid stenting were covered in detail as well. PMID- 26806502 TI - [PATHWAY-2 Study: spironolactone vs placebo, bisoprolol and doxazosin to determine optimal treatment of resistant hypertension. Spironolactone high effective in lowering blood pressure in drug resistant hypertension]. AB - The PATHWAY-2 study, funded by the British Heart Foundation, randomised 335 patients with resistant hypertension (already treated according to guidelines) to sequentially receive 12 weeks of spironolactone (25-50 mg), bisoprolol (5-10 mg), doxazosin (4-8 mg modified release) and placebo. The study design allowed drug comparisons in each patient, with 230 patients completing all cycles. Results showed that spironolactone reduced home systolic BP by 8.70 mm Hg more than placebo (<0.001), 4.26 mmHg more than bisoprolol/doxazosin (<0.001), 4.03 mm Hg more than doxazosin (<0.001), and by 4.48 mm Hg more than bisoprolol. By the end of the trial, there would only be 15 patients considered eligible for renal denervation trials in uncontrolled hypertension. PATHWAY-2 will have significant implications for patient recruitment in to other trials. PMID- 26806503 TI - [Monoclonal immunoglobulin (M-Ig) and skin diseases from the group of mucinoses- scleredema adultorum Buschke and scleromyxedema. Description of four cases and an overview of therapies]. AB - INTRODUCTION: The mucinoses of the type of scleredema and scleromyxedema are diseases marked by excessive production of mucin deposits in the skin and subcutaneous tissue, which causes skin hardening. The skin and subcutaneous deposits hamper the movement of limbs, the thorax as well as mouth. The same mechanism also damages other organs (the heart, lungs, oesophagus). It is probably caused by the stimulation of mucin production in fibroblasts by immunoglobulins, frequently monoclonal immunoglobulin. Therefore these diseases are typically associated with monoclonal gammopathy. CASE REPORTS: We describe a cohort of 4 patients, skin manifestations were twice identified as scleredema and twice as scleromyxedema. All the four patients had type IgG monoclonal immunoglobulin and had clonal plasma cells in the bone marrow proven by histologic examination and flow cytometry. Therefore we commenced chemotherapy in all of them. In one case this chemotherapy was ended by a high-dose chemotherapy with transplanting of autologous red blood cells. This therapy attained the complete disappearance of monoclonal immunoglobulin as well as cutaneous and extracutaneous manifestations of scleredema (obstipation). In one case chemotherapy led to partial hematologic remission and partial improvement of skin manifestations. The other two patients did not respond to standard chemotherapy. The condition of one of them resulted in dermato-neuro syndrome (confusion, somnolence passing into coma and grand mal seizure) and improved following an intensive treatment including also intravenous application of immunoglobulins in a dose of 2 g/per 1 kg weight. This patient has now been under long-term treatment with these immunoglobulins, during which the skin symptoms have significantly diminished, but the concentration of monoclonal immunoglobulin has not changed. The fourth patient not responding to standard chemotherapy was treated with intravenous immunoglobulins also in a dose of 2 g/per 1 kg of weight 1* in a month. After 4 applications the thickening of skin and subcutaneous tissue moderately diminished, so the range of possible movement of the upper limbs and neck became larger and the itchy skin morphs which accompanied the disease disappeared completely. CONCLUSION: It is possible to use chemotherapy and high-dose chemotherapy in the treatment of mucinosis associated with monoclonal gammopathy, as in the treatment of multiple myeloma. If such treatment is not possible or it has not attained disappearance of monoclonal immunoglobulin, improvement can be achieved through repeated application of intravenous immunoglobulins. The treatment with intravenous immunoglobulins in an immunomodulation dose of 2 g/per 1 kg of weight effects the moderation of skin manifestations, but it does not lead to the decrease in monoclonal immunoglobulin. PMID- 26806504 TI - [Uncorrected Tetralogy of Fallot--a case report of a 69-year-old patient]. AB - Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart defect. The actual treatment relies on cardio-surgery--complete correction within the infant age. Without surgery only 10% of subjects survived 3rd decade and only 3 5% of subjects were able to survive until their 40th. This particular paper is dedicated to case of a 69-years old male subject with positive history of uncorrected ToF due to his refusal of surgery, ischemic cardiac disease NYHA III IV and chronic kidney failure. This subject was hospitalized within the department of internal medicine due to several days of chest pain connected with lower extremities oedemas and dyspnoeic syndrome after minimal physical load. Provided echocardiography revealed pulmonary artery stenosis, severe tricuspid insufficiency, concentric hypertrophy of ventricles, ventricular septal defect, dextroposition of aorta and severe pericardial effusion. Chest X-ray proved massive pleura effussion. The actual conditions of subject improved significantly after onset of diuretics, antiarrhytmics and providing of pleural punction. Subject has been discharged. Cases of ToF presented within available sources in older population were associated with left ventricular hypertrophy and hypoplastic pulmonary artery and slow subpulmonal obstruction development which also presented within our subject. Left ventricular hypertrophy has a potential to develop continuously and therefore its benefits can be visible within adult age. PMID- 26806505 TI - [Medicine at a polar station in Antarctica]. AB - The paper describes specific aspects of work of a scientific expedition doctor and the stay and life at a polar research station in Antarctica. Apart from the outline of everyday problems, the first named author also learns about the history of medical practitioners working in Antarctica, writes about the results of the biomedical research activities conducted in the period of 2011-2014 and briefly describes the daily routine at a scientific polar station in Antarctica. PMID- 26806506 TI - What's new in pulmonary transplantation: Finding the right lung for every patient. PMID- 26806507 TI - Novel effect of rapamycin on experimental obliterative bronchiolitis. PMID- 26806508 TI - Journal changes and initiatives. PMID- 26806509 TI - Can multicenter registries determine the optimal timing of extubation after congenital heart surgery? PMID- 26806511 TI - Ex vivo lung perfusion: The magic bullet to cure sick donor lungs? PMID- 26806510 TI - Durability and clinical impact of tricuspid valve procedures in patients receiving a continuous-flow left ventricular assist device. AB - OBJECTIVE: Patients evaluated for a continuous-flow left ventricular assist device frequently present with severe right ventricular dysfunction with tricuspid regurgitation. Long-term outcomes of concurrent tricuspid valve procedures in continuous-flow left ventricular assist device implantation are unclear. METHODS: From May 2004 to December 2013, 336 patients received continuous-flow left ventricular assist devices. Among these, 8 patients with prior tricuspid valve procedures were excluded. At continuous-flow left ventricular assist device implantation, 76 patients underwent tricuspid valve procedures (group A), including 68 repairs and 8 replacements. The remaining 252 patients did not receive concurrent tricuspid valve procedures (group B). RESULTS: Preoperatively, group A had higher central venous pressure/pulmonary capillary wedge pressure (P = .032), total bilirubin (P = .009), and percentage of moderate or greater tricuspid regurgitation (98.7% vs 18.8%; P < .001). In group A, cardiopulmonary bypass time (136 +/- 52.0 minutes vs 83.9 +/- 38.8 minutes; P < .001), intraoperative platelet use (13.6 +/- 6.70 units vs 11.7 +/- 5.92 units; P = .042), and bleeding requiring reoperation (27.5% vs 16.7%; P = .046) were significantly increased. In-hospital mortality was similar (10.5% vs 6.4%; P = .22). On-device 2-year survival was 73.9% in group A and 74.2% in group B (P = .24). At 2 years, mean cumulative readmissions for right heart failure was 0.21 in group A and 0.27 in group B (P = .95). A generalized linear mixed-effects model showed that tricuspid valve procedures are protective for developing future significant tricuspid regurgitation (odds ratio, 0.38; 95% confidence interval, 0.19-0.76; P = .006). CONCLUSIONS: Concomitant tricuspid valve procedures at continuous-flow left ventricular assist device implantation can be performed safely and are protective against worsening tricuspid regurgitation during the first 2 years of support. PMID- 26806512 TI - Topical amiodarone to prevent postoperative atrial fibrillation: Need for further study. PMID- 26806513 TI - Considerations for the success of topical amiodarone to prevent postoperative atrial fibrillation. PMID- 26806514 TI - Something old, something new: Marrying 2 approaches to resect an ectopic parathyroid adenoma. PMID- 26806515 TI - Impaired ergosterol biosynthesis mediated fungicidal activity of Co(II) complex with ligand derived from cinnamaldehyde. AB - In this study, we have used aldehyde function of cinnamaldehyde to synthesize N, N'-Bis (cinnamaldehyde) ethylenediimine [C20H20N2] and Co(II) complex of the type [Co(C40H40N4)Cl2]. The structures of the synthesized compounds were determined on the basis of physiochemical analysis and spectroscopic data ((1)H NMR, FTIR, UV visible and mass spectra) along with molar conductivity measurements. Anticandidal activity of cinnamaldehyde its ligand [L] and Co(II) complex was investigated by determining MIC80, time-kill kinetics, disc diffusion assay and ergosterol extraction and estimation assay. Ligand [L] and Co(II) complex are found to be 4.55 and 21.0 folds more efficient than cinnamaldehyde in a liquid medium. MIC80 of Co(II) complex correlated well with ergosterol inhibition suggesting ergosterol biosynthesis to be the primary site of action. In comparison to fluconazole, the test compounds showed limited toxicity against H9c2 rat cardiac myoblasts. In confocal microscopy propidium iodide (PI) penetrates the yeast cells when treated with MIC of metal complex, indicating a disruption of cell membrane that results in imbibition of dye. TEM analysis of metal complex treated cells exhibited notable alterations or damage to the cell membrane and the cell wall. The structural disorganization within the cell cytoplasm was noted. It was concluded that fungicidal activity of Co(II) complex originated from loss of membrane integrity and a decrease in ergosterol content is only one consequence of this. PMID- 26806516 TI - Cardiac gene therapy: a call for basic methods development. PMID- 26806517 TI - Pharmacogenetics of lithium response: close to clinical practice? PMID- 26806521 TI - The effect of an Enhanced Recovery Program in elective retroperitoneal abdominal aortic aneurysm repair. AB - OBJECTIVE: Enhanced Recovery Programs (ERPs) have been introduced to accelerate postoperative recovery and are mainly focused on decreasing the surgical stress response. Limited data are available regarding the implementation of ERPs in patients who undergo abdominal aortic aneurysm (AAA) repair using the retroperitoneal approach. The aims of this study were: (1) to evaluate the implementation of an ERP in patients who underwent elective retroperitoneal AAA repair; and (2) to define independent predictors of prolonged hospital length of stay (LOS) in these patients. METHODS: This was a retrospective cohort study on 221 patients who underwent elective AAA repair via a retroperitoneal approach from 2005 through 2013 at an Italian university hospital. Patients who received surgery from 2008 through 2013 and enrolled in an ERP (n = 130) were compared with those who received surgery from 2005 through 2007 and managed with traditional perioperative care (n = 91). RESULTS: Patient characteristics were comparable between groups. Intensive care unit admissions were prevalent among patients who received traditional care vs patients in the ERP (P < .01). ERP patients had fewer major (P < .01) and minor (P = .019) complications, and mortality was similar between groups. Complete functional recovery was achieved earlier in ERP patients vs controls (P < .01). Patients in the ERP group left the hospital earlier than controls (P < .01). No readmission <=30 days were reported in the ERP group. Age >=65 years and being in a conventional care protocol were found to be independent predictors of prolonged hospital LOS. CONCLUSIONS: The implementation of an ERP after elective AAA repair using a retroperitoneal approach reduced postoperative intensive care unit admission, accelerated functional recovery, and decreased morbidity and LOS with no readmission <=30 days. Age >=65 years and conventional perioperative care were the only independent predictors of prolonged LOS. PMID- 26806522 TI - Minimal correlation between physical exercise capacity and daily activity in patients with intermittent claudication. AB - BACKGROUND: Walking capacity measured by a treadmill test (TT) reflects the patient's maximal capacity in a controlled setting and is part of the physical exercise capacity (PEC). Daily physical activity (PA) is defined as the total of actively freely produced movements per day. A lower PA level has been increasingly recognized as a strong predictor of increased morbidity and mortality in patients with intermittent claudication (IC). Recent insights suggested that an increased PEC does not automatically lead to an increase in daily PA. However, the precise relation between PEC and PA in patients with IC is still unclear. METHODS: A cross-sectional study was conducted to assess the association between several PEC outcomes and PA in a general IC population. PEC was determined by well-established tests (Gardner-Skinner TT, a physical performance battery, a timed up-and-go test, and a 6-minute walk test distance). PA was obtained during 7 consecutive days using a triaxial accelerometer (Dynaport MoveMonitor; McRoberts BV, The Hague, The Netherlands). Five PA components (lying, sitting, standing, shuffling, and locomotion) and four parameters (total duration, number of periods, mean duration per period, and mean movement intensity per period) were analysed. Correlation coefficients between PEC and PA components were calculated. RESULTS: Data of 46 patients were available for analysis. Patients were sedentary (sitting and lying) during 81% of the day and were physically active (standing, shuffling, and locomotion) for the remaining 19% of the time. Correlations between PEC outcomes and PA ranged from very weak (0.025) to moderate (0.663). Moderate correlations (as therefore assumed to be relevant) were only found for outcomes of both the TT and 6-minute walk test and the locomotion components of PA. For instance, functional claudication distance (measured by TT) and number of steps per day correlated reasonably well (Spearman correlation rho = 0.663; P < .01). CONCLUSIONS: Exercise capacity and PA correlate minimally in patients with IC. PA may be preferred as a novel outcome measure and future treatment target in patients with IC. PMID- 26806523 TI - Volume analysis of true and false lumens in acute complicated type B aortic dissections after thoracic endovascular aortic repair with stent grafts alone or with a composite device design. AB - OBJECTIVE: This study compared the 12-month evolution of the aortic volume in patients who underwent thoracic endovascular aortic repair (TEVAR) with stent grafts alone or a composite device (Zenith TX2 stent graft and Zenith Dissection stent; Cook Medical, Bloomington, Ind) for acute (<=2 weeks from onset) complicated type B aortic dissection. METHODS: This was a retrospective analysis comparing prospectively collected data from 45 patients who underwent standard TEVAR repair at three European institutions (TEVAR group) and 39 patients in the Study of Thoracic Aortic type B Dissection using Endoluminal Repair (STABLE I) study who received a composite device (STABLE group). The analysis included consecutive patients treated for acute, complicated type B dissection and with available baseline and 12-month computed tomography imaging. Volume analysis was performed by using a semiautomated centerline algorithm. RESULTS: Baseline demographics, medical history, extent of dissection, and clinical indications were largely similar between the two groups. There was no difference in the length of aorta covered by stent grafts (167 +/- 47 mm in STABLE and 184 +/- 49 mm in TEVAR; P = .11). The STABLE group had an initial larger false lumen volume in the thoracic (203 +/- 72 cm(3) vs 162 +/- 74 cm(3); P = .01) and abdominal aorta (63 +/- 29 cm(3) vs 36 +/- 27 cm(3); P < .001). In the thoracic aorta, each group exhibited a significant increase in true lumen volume and a significant decrease in false lumen volume through 12 months. The total aortic volume increased significantly in the STABLE group (P < .001) but not in the TEVAR group. In the abdominal aorta, only the STABLE group exhibited a significant increase in the true lumen volume (P < .001) and a significant decrease in the false lumen volume (P = .004) postoperatively. At 12 months, the true lumen continued to increase significantly in the STABLE group (P = .03). However, no statistically significant difference was detected when the two groups were compared for the overall changes in the true lumen and false lumen volumes from preprocedure to 12 months, and both groups exhibited a statistically significant increase in total abdominal aortic volume at 12 months. There was no statistical difference between the two groups in the proportions of patients who experienced >10% changes in the thoracic or abdominal total lumen volume after TEVAR. Patients in the two groups (all survived 12 months) had similar clinical outcomes, including rupture, conversion, and reinterventions. CONCLUSIONS: According to this volume analysis, thoracic endografting for acute complicated type B dissections promotes significant thoracic aortic remodeling. The use of bare-metal dissection stents leads to significant true lumen expansion and false lumen regression in the early follow-up and to subsequent continued true lumen expansion in the abdominal aorta; however, a definitive benefit in aortic remodeling over TEVAR alone was not demonstrated at 1 year. PMID- 26806525 TI - Accelerated 3D echo-planar imaging with compressed sensing for time-resolved hyperpolarized 13 C studies. AB - PURPOSE: To enable large field-of-view, time-resolved volumetric coverage in hyperpolarized 13 C metabolic imaging by implementing a novel data acquisition and image reconstruction method based on the compressed sensing framework. METHODS: A spectral-spatial pulse for single-resonance excitation followed by a symmetric echo-planar imaging (EPI) readout was implemented for encoding a 72 * 18 cm2 field of view at 5 * 5 mm2 resolution. Random undersampling was achieved with blipped z-gradients during the ramp portion of the echo-planar imaging readout. The sequence and reconstruction were tested with phantom studies and consecutive in vivo hyperpolarized 13 C scans in rats. Retrospectively and prospectively undersampled data were compared on the basis of structural similarity in the reconstructed images and the quantification of the lactate-to pyruvate ratio in rat kidneys. RESULTS: No artifacts or loss of resolution are evident in the compressed sensing reconstructed images acquired with the proposed sequence. Structural similarity analysis indicate that compressed sensing reconstructions can accurately recover spatial features in the metabolic images evaluated. CONCLUSION: A novel z-blip acquisition sequence for compressed sensing accelerated hyperpolarized 13 C 3D echo-planar imaging was developed and demonstrated. The close agreement in lactate-to-pyruvate ratios from both retrospectively and prospectively undersampled data from rats shows that metabolic information is preserved with acceleration factors up to 3-fold with the developed method. Magn Reson Med 77:538-546, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26806526 TI - Pathogenesis-Related Proteins Limit the Retention of Condensed Tannin Additions to Red Wines. AB - Exogenous additions of condensed tannin (CT) to must or wine are a common winemaking practice, but many studies have reported inexplicably low and variable retention of added CT. We observed that additions of purified CT to red wines can result in the formation of an insoluble precipitate with high nitrogen content. Proteomic analysis of the precipitant identified several classes of pathogenesis related proteins. Proteins in juices and red wines were quantitated by SDS-PAGE and were highest in native Vitis spp., followed by interspecific hybrids and Vitis vinifera. Wine protein was positively correlated with the ratio of juice protein to the quantity of tannin derived from fruit. The binding of added CT by wine protein could be well modeled by the Freundlich equation. These observations may explain the poor CT retention in previous studies, particularly for interspecific hybrids, and also indicate that protein removal during winemaking may improve exogenous CT retention. PMID- 26806518 TI - Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study. AB - BACKGROUND: Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified. METHODS: Here, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis. FINDINGS: A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1.37 * 10(-8); rs78015114, p=1.31 * 10(-8); rs74795342, p=3.31 * 10(-9); and rs75222709, p=3.50 * 10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0.03268, hazard ratio 3.8, 95% CI 1.1-13.0). INTERPRETATION: The response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings. FUNDING: Deutsche Forschungsgemeinschaft, National Institute of Mental Health Intramural Research Program. PMID- 26806527 TI - Strategies for target identification of antimicrobial natural products. AB - Covering: 2000 to 2015Despite a pervasive decline in natural product research at many pharmaceutical companies over the last two decades, natural products have undeniably been a prolific and unsurpassed source for new lead antibacterial compounds. Due to their inherent complexity, natural extracts face several hurdles in high-throughout discovery programs, including target identification. Target identification and validation is a crucial process for advancing hits through the discovery pipeline, but has remained a major bottleneck. In the case of natural products, extremely low yields and limited compound supply further impede the process. Here, we review the wealth of target identification strategies that have been proposed and implemented for the characterization of novel antibacterials. Traditionally, these have included genomic and biochemical based approaches, which, in recent years, have been improved with modern-day technology and better honed for natural product discovery. Further, we discuss the more recent innovative approaches for uncovering the target of new antibacterial natural products, which have resulted from modern advances in chemical biology tools. Finally, we present unique screening platforms implemented to streamline the process of target identification. The different innovative methods to respond to the challenge of characterizing the mode of action for antibacterial natural products have cumulatively built useful frameworks that may advocate a renovated interest in natural product drug discovery programs. PMID- 26806530 TI - Preparation of graphene oxide and polymer-like quantum dots and their one- and two-photon induced fluorescence properties. AB - A simple, effective and green bottom-up method for the synthesis of highly fluorescent N doped graphene oxide quantum dots (GOQDs) and polymer-like quantum dots (PQDs) was developed on the basis of rapid one-step microwave assisted pyrolysis of citric acid (CA) and diethylenetriamine (DETA) in different reaction solvents. Both one-photon-induced and two-photon-induced photoluminescence (PL) properties of the resultant GOQDs and PQDs were characterized and analyzed. The one-photon-induced PL quantum yields (QY) of GOQDs and PQDs reached 39.8 and 74.0%, respectively, which are high enough to exhibit strong photoluminescence (PL) emission even under daylight excitation. The origin of the PL behavior and PL quenching mechanism was explored in terms of the interaction between the functional groups on the surfaces of GOQDs or PQDs and Hg(2+). Furthermore, due to the excellent selectivity and sensitivity of the GOQDs and PQDs to Hg(2+), the quantum dots might be used for quantitative detection of Hg(2+) in aqueous solution. PMID- 26806528 TI - Biofortified indica rice attains iron and zinc nutrition dietary targets in the field. AB - More than two billion people are micronutrient deficient. Polished grains of popular rice varieties have concentration of approximately 2 MUg g(-1) iron (Fe) and 16 MUg g(-1) zinc (Zn). The HarvestPlus breeding programs for biofortified rice target 13 MUg g(-1) Fe and 28 MUg g(-1) Zn to reach approximately 30% of the estimated average requirement (EAR). Reports on engineering Fe content in rice have shown an increase up to 18 MUg g(-1) in glasshouse settings; in contrast, under field conditions, 4 MUg g(-1) was the highest reported concentration. Here, we report on selected transgenic events, field evaluated in two countries, showing 15 MUg g(-1) Fe and 45.7 MUg g(-1) Zn in polished grain. Rigorous selection was applied to 1,689 IR64 transgenic events for insert cleanliness and, trait and agronomic performances. Event NASFer-274 containing rice nicotianamine synthase (OsNAS2) and soybean ferritin (SferH-1) genes showed a single locus insertion without a yield penalty or altered grain quality. Endosperm Fe and Zn enrichment was visualized by X-ray fluorescence imaging. The Caco-2 cell assay indicated that Fe is bioavailable. No harmful heavy metals were detected in the grain. The trait remained stable in different genotype backgrounds. PMID- 26806533 TI - Analysis of the in vivo proliferative capacity of a whole cell cancer vaccine. AB - A polyvalent therapeutic cancer cell vaccine containing three viable, irradiated, replication-incompetent melanoma cell lines (Canvaxin) was administered to over 2500 patients in various clinical studies. This study examines the fate of Canvaxin cells in 16 patients with Stage II, III or IV melanoma, with special attention on assessing the capacity of the vaccine cells to replicate. The survival time and the potential proliferative capacity of irradiated Canvaxin cells in humans was studied by histologic examination of biopsies of injection sites over a two-week period. The overall results show that the vaccine cell mitotic index in skin biopsies (0.12%) was approximately 6 times lower than the control value (0.71%). Similarly, there was an overall trend toward a decrease in mitotic figures during the two week observation periods. Also, there was a trend towards a decrease in the number of vaccine cells and mitotic figures with increasing cycles. The data indicate that Canvaxin cells do not proliferate after intra-dermal injection, and that cells typically associated with an immune response are present at the inoculation sites. PMID- 26806534 TI - Tone regulation in giraffe retinal arterioles. PMID- 26806535 TI - Direct conjugate alkylation of alpha,beta-unsaturated carbonyls by Ti(III) catalysed reductive umpolung of simple activated alkenes. AB - The titanium(iii)-catalysed cross-selective reductive umpolung of Michael acceptors represents a unique direct conjugate beta-alkylation reaction. It allows the cross-selective preparation of 1,6- and 1,4-difunctionalised building blocks without the requirement of stoichiometric organometallic reagents. In this full paper, the development and scope of the titanium(iii)-catalysed cross selective reductive umpolung of Michael-acceptors is described. Based on the observed selectivities and additional mechanistic experiments a refined mechanistic proposal is presented. PMID- 26806536 TI - Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats. AB - Rat cytochrome P450 (CYP) exhibits inter-strain differences, but their analysis has been scattered across studies under different conditions. To identify these strain differences in CYP more comprehensively, mRNA expression, protein expression and metabolic activity among Wistar (WI), Sprague Dawley (SD), Dark Agouti (DA) and Brown Norway (BN) rats were compared. The mRNA level and enzymatic activity of CYP1A1 were highest in SD rats. The rank order of Cyp3a2 mRNA expression mirrored its protein expression, i.e., DA>BN>SD>WI, and was similar to the CYP3A2-dependent warfarin metabolic activity, i.e., DA>SD>BN>WI. These results suggest that the strain differences in CYP3A2 enzymatic activity are caused by differences in mRNA expression. Cyp2b1 mRNA levels, which were higher in DA rats, did not correlate with its protein expression or enzymatic activity. This suggests that the strain differences in enzymatic activity are not related to Cyp2b1 mRNA expression. In conclusion, WI rats tended to have the lowest CYP1A1, 2B1 and 3A2 mRNA expression, protein expression and enzymatic activity among the strains. In addition, SD rats had the highest CYP1A1 mRNA expression and activity, while DA rats had higher CYP2B1 and CYP3A2 mRNA and protein expression. These inter-strain differences in CYP could influence pharmacokinetic considerations in preclinical toxicological studies. PMID- 26806537 TI - Babesia gibsoni internal transcribed spacer 1 region is highly conserved amongst isolates from dogs across Japan. AB - Babesia gibsoni is a tick-borne apicomplexan parasite of dogs that often causes fever and hemolytic anemia with highly variable clinical outcome. In this study, we sequenced the 254bp Internal Transcribed Spacer 1 region (ITS1) of 54 B. gibsoni isolates from 14 different geographical regions of Japan. The 54 isolates shared high sequence identity with each other and with B. gibsoni isolates reported in GenBank database (97.2-100%). Consistent with previous reports, phylogenetic analysis showed that B. gibsoni isolates from Japan formed the same clade with those from U.S.A., Australia, India and Taiwan. Our finding indicates that B. gibsoni ITS1 region is highly conserved among isolates from dogs in Japan, making it a useful genetic marker for molecular epidemiology of the parasite. PMID- 26806538 TI - The impact of non-motor symptoms on the quality of life of Parkinson's disease patients: a longitudinal study. AB - BACKGROUND AND PURPOSE: Non-motor symptoms (NMSs) are common amongst patients with Parkinson's disease (PD); however, little is known about their influence on the health-related quality of life (QoL) over a defined follow-up period. The study was aimed to establish the impact of NMSs on the QoL of patients with PD over a 2-year follow-up period. METHOD: A total of 227 newly referred PD patients were prospectively recruited between 2013 and 2014. The Non-Motor Symptoms Scale was used to evaluate NMSs burden whilst QoL was assessed with the Parkinson's Disease Questionnaire-39 items. Motor disabilities were assessed using the Part III (motor) Unified Parkinson's Disease Rating Scale (UPDRSm). RESULTS: The mean age was 64.37 (10.18) years; 59.9% were males and a majority (89.0%) were ethnic Chinese. Almost 65% were unemployed and 84.6% had attained no more than secondary level of education. In the univariate analysis, total NMSs burden, age, gender, subsequent visit, Hoehn and Yahr staging, disease duration and UPDRSm score were individually predictive of change in the Parkinson's Disease Questionnaire Summary Index score from baseline to follow-up visit. However, in the multivariate analysis, total NMSs burden significantly predicted the QoL scores whilst motor scores did not. Specifically, NMS domains 2 (sleep/fatigue), 3 (mood/apathy) and 5 (attention/memory) were most significantly predictive of QoL change. CONCLUSION: Unlike motor disabilities, NMSs burden, in particular sleep, mood and attention, have a significant impact on the QoL of PD patients over a 2 year follow-up period. PMID- 26806539 TI - A single short session of media perfusion induces osteogenesis in hBMSCs cultured in porous scaffolds, dependent on cell differentiation stage. AB - Perfusing culture media through porous cell-seeded scaffolds is now a common approach within many tissue engineering strategies. Human bone-marrow derived mesenchymal stem cells (hBMSC) are a clinically valuable source of osteoprogenitors that respond to mechanical stimuli. However, the optimal mechanical conditions for their osteogenic stimulation in vitro have not been defined. Whereas the effects of short durations of media fluid flow have been studied in monolayers of osteoblastic cells, in 3D culture continuous or repeated perfusion is usually applied. Here, we investigated whether a short, single perfusion session applied to hBMSCs cultured in 3D would enhance their osteogenesis in vitro. We cultured hBMSCs on gelatine-coated, porous polyurethane scaffolds with osteogenic supplements and stimulated them with a single 2-h session of unidirectional, steady, 2.5 mL/min media perfusion, at either early or late stages of culture in 3D. Some cells were pre-treated in monolayer with osteogenic supplements to advance cell differentiation, followed by 3D culture also with the osteogenic supplements. We report that this single, short session of media perfusion can markedly enhance the expression of bone-related transcription and growth factors, and matrix components, by hBMSCs but that it is more effective when cells reach the pre-osteoblast or osteoblast differentiation stage. These findings could aid in the optimization of 3D culture protocols for efficient bone tissue engineering. Biotechnol. Bioeng. 2016;113: 1814-1824. (c) 2016 Wiley Periodicals, Inc. PMID- 26806541 TI - Foreword: Thoracic Insufficiency Syndrome. PMID- 26806540 TI - Activation of transient receptor potential ankyrin 1 by quercetin and its analogs. AB - The agonistic activity of quercetin and its analogs towards the transient receptor potential ankyrin 1 (TRPA1) has been experimentally investigated. The human TRPA1 was expressed in HEK293T cells using a tetracycline-inducible system. The activation of TRPA1 was evaluated by a fluo-4 fluorescence assay based on calcium sensing. The results of a structure-activity relationship study led to the selection of six flavonoids, all of which activated the TRPA1 channel in a dose-dependent manner. Notably, the activation of TRPA1 by these flavonoid aglycones was completely inhibited by the co-treatment of the HEK293T cells with the TRPA1-specific antagonist, HC-030031. Several flavonoid glycosides and metabolites were also evaluated, but did not activate the TRPA1 except for methylated quercetin. On the other hand, TRPV1 (vanilloid receptor) did not respond to any of the flavonoids evaluated in this study. Therefore, these data suggest that the flavonoids would be promising ligands for the TRPA1. PMID- 26806542 TI - An investigation into the effects of applying a lumbar Maitland mobilisation at different frequencies on sympathetic nervous system activity levels in the lower limb. AB - BACKGROUND: Oscillatory Maitland mobilisations are commonly used in the management of lower back pain with research suggesting that mobilisations at 2 Hz may excite the sympathetic nervous system (SNS) more than sustained pressure glides or 0.5 Hz oscillatory mobilisations. OBJECTIVES: Investigate the effects of increasing the oscillation frequency greater than 2 Hz. DESIGN: A double blind, placebo-controlled, independent group experimental design. METHOD: Sixty healthy male volunteers were randomly allocated to one of four groups; a control group (no contact), placebo group (sustained static pressure to L4 vertebra), and two intervention groups receiving a centrally applied postero-anterior mobilisation applied at either 2 Hz or 3 Hz for three 1-min periods. SNS activity was recorded by a blinded data collector by continuous skin conductance (SC) activity levels in the feet using a Biopac MP35 electrodermal amplifier. Participants were blinded to their group allocation which was further validated by a post-experiment questionnaire (p > 0.05). RESULTS: The magnitude of sympathoexcitatory response was greatest for the 3 Hz mobilisation (20%) compared with the 2 Hz mobilisation (12%), placebo (-1%) and control conditions (3%). Only the 3 Hz group demonstrated statistical significance when compared to placebo intervention (p = 0.002), and the control group (p = 0.02). CONCLUSION: SC changes reflect those of previous studies using lumbar mobilisations at 2 Hz, however the 3 Hz group was found to have a greater magnitude of effect worthy of consideration within research and clinical settings. These findings provide preliminary evidence to support the use of 3 Hz oscillatory mobilisations to affect a greater magnitude of SNS activity than those previously reported (0.5, 1.5 and 2 Hz). PMID- 26806544 TI - Engineering carpel-specific cold stress tolerance: a case study in Arabidopsis. AB - Climate change predictions forecast an increase in early spring frosts that could result in severe damage to perennial crops. For example, the Easter freeze of April 2007 left several states in the United States reporting a complete loss of that year's peach crop. The most susceptible organ to early frost damage in fruit trees is the carpel, particularly during bloom opening. In this study, we explored the use of a carpel-specific promoter (ZPT2-10) from petunia (Petunia hybrida var. Mitchell) to drive expression of the peach dehydrin PpDhn1. In peach, this gene is exceptionally responsive to low temperature but has not been observed to be expressed in carpels. This study examined carpel-specific properties of a petunia promoter driving the expression of the GUS gene (uidA) in transgenic Arabidopsis flowers and developed a carpel-specific ion leakage test to assess freezing tolerance. A homozygous Arabidopsis line (line 1-20) carrying the petunia ZPT2-10 promoter::PpDhn1 construct was obtained and freezing tolerance in the transgenic line was compared with an untransformed control. Overexpression of PpDhn1 in line 1-20 provided as much as a 1.9 degrees C increase in carpel freezing tolerance as measured by electrolyte leakage. PMID- 26806545 TI - Transition from freshwater to seawater reshapes the skin-associated microbiota of Atlantic salmon. AB - Knowledge concerning shifts in microbiota is important in order to elucidate the perturbations in the mucosal barrier during the transitional life stages of the host. In the present study, a 16S rRNA gene sequencing technique was employed to examine the compositional changes and presumptive functions of the skin associated bacterial communities of Atlantic salmon reared under controlled laboratory conditions and transferred from freshwater to seawater. Proteobacteria was the dominant phylum in salmon from both freshwater (45%) and seawater (above 89%). Bacteroidetes, Actinobacteria, Firmicutes, Cyanobacteria and Verrucomicrobia were the most abundant phyla in salmon from freshwater. The transition to seawater influenced the OTU richness and evenness. The high abundance (~62%) of the genus Oleispira made Proteobacteria the most significantly abundant phylum in salmon from seawater. The predictive functional profile suggested that the communities had the ability to extract energy from amino acids in order to maintain their metabolism and scavenge and biosynthesise compounds to make structural changes and carry out signalling for their survival. These findings need to be further explored in relation to metabolic processes, the fish genotype, and the environment. PMID- 26806546 TI - Impact of a soy drink on climacteric symptoms: an open-label, crossover, randomized clinical trial. AB - OBJECTIVES: The objective of this study is to evaluate the effects of a soy drink with a high concentration of isoflavones (ViveSoy(r)) on climacteric symptoms. METHODS: An open-label, controlled, crossover clinical trial was conducted in 147 peri- and postmenopausal women. Eligible women were recruited from 13 Spanish health centers and randomly assigned to one of the two sequence groups (control or ViveSoy(r), 500 mL per day, 15 g of protein and 50 mg of isoflavones). Each intervention phase lasted for 12 weeks with a 6-week washout period. Changes on the Menopause Rating Scale and quality of life questionnaires, as well as lipid profile, cardiovascular risk and carbohydrate and bone metabolism were assessed. Statistical analysis was performed using a mixed-effects model. RESULTS: A sample of 147 female volunteers was recruited of which 90 were evaluable. In both sequence groups, adherence to the intervention was high. Regular consumption of ViveSoy(r) reduced climacteric symptoms by 20.4% (p = 0.001) and symptoms in the urogenital domain by 21.3% (p < 0.05). It also improved health-related quality life by 18.1%, as per the MRS questionnaire (p <0.05). CONCLUSION: Regular consumption of ViveSoy(r) improves both the somatic and urogenital domain symptoms of menopause, as well as health-related quality of life in peri- and postmenopausal women. PMID- 26806547 TI - TIMAP-protein phosphatase 1-complex controls endothelin-1 production via ECE-1 dephosphorylation. AB - Endothelin induced signaling pathways can affect blood pressure and vascular tone, but the influence of endothelins on tumor cells is also significant. We have detected elevated endothelin-1 secretion from TIMAP (TGF-beta inhibited membrane associated protein) depleted vascular endothelial cells. The autocrine signaling activated by the elevated endothelin-1 level through the ETB receptors evoked an angiogenic-like phenotype, the cells assumed an elongated morphology, and enhanced tube formation and wound healing abilities. The depleted protein, TIMAP, is a highly specific and abundant protein in the endothelial cells, and it is a regulatory/targeting subunit for the catalytic subunit of protein phosphatase 1 (PP1c). Protein-protein interaction between the TIMAP-PP1c complex and the endothelin converting enzyme-1 (ECE-1) was detected, the latter of which is a transmembrane protein that produces the biologically active 21-amino acid form of endothelin-1 from proendothelin. The results indicate that silencing of TIMAP induces a reduction in TIMAP-PP1c activity connected to ECE-1. This leads to an increase in the amount of ECE-1 protein in the plasma membrane and a consequent increase in endothelin-1 secretion. Similarly, activation of PKC, the kinase responsible for ECE-1 phosphorylation increased ECE-1 protein level in the membrane fraction of the endothelial cells. The elevated ECE-1 level was mitigated in time in normal cells, but was clearly preserved in TIMAP-depleted cells. Overall, our results indicate that PKC-phosphorylated ECE-1 is a TIMAP PP1c substrate and this phosphatase complex has an important role in endothelin-1 production of EC through the regulation of ECE-1 activity. PMID- 26806548 TI - Response to immunotherapy in a patient with Landau-Kleffner syndrome and GRIN2A mutation. AB - Landau-Kleffner syndrome (LKS) has been demonstrated in the past to respond to immunotherapy. Recently, some cases of LKS have been shown to be secondary to glutamate receptor (GRIN2A) mutations. Whether such cases respond to immunotherapy is not known. Here, we present the case of a 3-year-old boy with LKS found to have a GRIN2A heterozygous missense mutation, whose clinical symptoms and EEG responded to a course of combination oral steroids and monthly infusions of intravenous immunoglobulin. He then relapsed after discontinuation of this therapy, and responded again after a second course of intravenous immunoglobulin. We conclude that immunotherapy should be considered as a therapeutic option in patients with LKS who are also found to harbour GRIN2A mutations. PMID- 26806550 TI - Variceal Hemorrhage in a Patient With Hepatitis C Virus Cirrhosis in Whom Liver Synthetic Function had Normalized After Viral Elimination. PMID- 26806551 TI - DDAH1 deficiency promotes intracellular oxidative stress and cell apoptosis via a miR-21-dependent pathway in mouse embryonic fibroblasts. AB - Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, is degraded by dimethylarginine dimethylaminohydrolase 1 (DDAH1). Emerging evidence suggests that plasma ADMA accumulation, DDAH1 activity/expression reduction, and microRNA-21 (miR-21) upregulation are linked to disease pathology, but the mechanisms remain largely unknown. In the present study, we assessed the potential role of the ADMA-DDAH1-miR-21 pathway in the regulation of the cellular redox state and apoptosis using wild-type (WT) and DDAH1-knockout (KO) immortalized mouse embryonic fibroblasts (MEFs). DDAH1 deficiency significantly increased ADMA levels, enhanced cellular oxidative stress, and rendered cells more vulnerable to apoptosis induced by tert-butyl hydroperoxide (tBHP) or A23187. However, treatment with exogenous ADMA (1-80MUM) for 24h or for a prolonged period (10MUM, 10 passages) in WT MEFs had no marked effect on intracellular reactive oxygen species (ROS) and apoptosis sensitivity. Interestingly, miR-21 expression was significantly increased, by 4 fold, in DDAH1(-/-) MEFs, and the induction of miR-21 by DDAH1 deficiency was dependent on oxidative stress and NF-kappaB activation. Inhibition of DDAH1 activity by PD 404182 also increased miR-21 expression. Furthermore, inhibition of miR-21 with a lentiviral vector in DDAH1(-/-) MEFs significantly upregulated SOD2 expression and the attenuated oxidative stress and apoptosis induced by tBHP or A23187. Taken together, our results suggest that DDAH1 not only acts as an enzyme degrading ADMA but also controls cellular oxidative stress and apoptosis via a miR-21-dependent pathway. PMID- 26806552 TI - Factors that determine catastrophic expenditure for tuberculosis care: a patient survey in China. AB - BACKGROUND: Tuberculosis (TB) often causes catastrophic economic effects on both the individual suffering the disease and their households. A number of studies have analyzed patient and household expenditure on TB care, but there does not appear to be any that have assessed the incidence, intensity and determinants of catastrophic health expenditure (CHE) relating to TB care in China. That will be the objective of this paper. METHODS: The data used for this study were derived from the baseline survey of the China Government - Gates Foundation TB Phase II program. Our analysis included 747 TB cases. Catastrophic health expenditure for TB care was estimated using two approaches, with households defined as experiencing CHE if their annual expenditure on TB care: (a) exceeded 10 % of total household income; and (b) exceeded 40 % of their non-food expenditure (capacity to pay). Chi-square tests were used to identify associated factors and logistic regression analysis to identify the determinants of CHE. RESULTS: The incidence of CHE was 66.8 % using the household income measure and 54.7 % using non-food expenditure (capacity to pay). An inverse association was observed between CHE rates and household income level. Significant determinants of CHE were: age, household size, employment status, health insurance status, patient income as a percentage of total household income, hospitalization and status as a minimum living security household. Factors including gender, marital status and type of TB case had no significant associations with CHE. CONCLUSIONS: Catastrophic health expenditure incidence from TB care is high in China. An integrated policy expanding the free treatment package and ensuring universal coverage, especially the height of UHC for TB patients, is needed. Financial and social protection interventions are essential for identified at-risk groups. PMID- 26806553 TI - Mouthpart structure in the woolly apple aphid Eriosoma lanigerum (Hausmann) (Hemiptera: Aphidoidea: Pemphigidae). AB - Mouthparts are important sensory and feeding structures in insects and differences in mouthpart structure reflect differences among lineages in feeding strategy and behavior. The woolly apple aphid (WAA), Eriosoma lanigerum (Hausmann), is an important pest of apple orchards worldwide, causing direct damage through feeding by the highly specialized piercing-sucking mouthparts. To obtain a better understanding of feeding, the morphology of mouthparts of the WAA was examined using scanning electron microscopy (SEM). The mouthparts of E. lanigerum are similar to those of previously studied aphid species in most aspects and composed of a cone-shaped labrum, a tube-like, four-segmented labium with a deep groove on the anterior side, and a stylet fascicle consisting of two mandibular and two maxillary stylets. The sculpturing on the lateral margin of the distal extremity of the maxillary stylets and a dentate protuberance at the very sharp tip are newly observed features that distinguish E. lanigerum from other aphids and Auchenorrhyncha. Also, there is a common duct in E. lanigerum as based on SEM. Two types of sensilla trichodea and three types of sensilla basiconica occur at different locations on the labium; the labial tip has eight pairs of small sensilla basiconica. The morphology of the mouthparts and the distribution of sensilla located on the labium in E. lanigerum are discussed with respect to their possible taxonomic and functional significance. PMID- 26806554 TI - Introduction: Fossils as Living Beings. PMID- 26806555 TI - Levo-tetrahydropalmatine, a natural, mixed dopamine receptor antagonist, inhibits methamphetamine self-administration and methamphetamine-induced reinstatement. AB - Despite the high prevalence of methamphetamine (METH) use, no FDA-approved pharmacological treatment is currently available for individuals with a METH addiction. Levo-tetrahydropalmatine (l-THP) is an alkaloid substance derived from corydalis and stephania that has been used in traditional Asian medicine for its analgesic, sedative and hypnotic properties. Previous pharmacological studies of l-THP indicated that it not only binds to D1 and D2 receptors but also has a low affinity for D3 receptors and may function as an antagonist. The unique pharmacological profile of l-THP suggests that it may have potential therapeutic effects on drug addiction; however, the effects of l-THP in individuals with METH addictions are largely unknown. In this study, we investigated the effects of l THP on METH self-administration and METH-induced reinstatement. In our experiments, l-THP (1.25, 2.50 and 5.00 mg/kg, i.p.) decreased METH self administration under the fixed-ratio 1 schedule. l-THP (2.50 and 5.00 mg/kg, i.p) also prevented the METH-induced reinstatement of METH-seeking behaviors. Interestingly, l-THP (1.25 and 2.50mg/kg, i.p) did not affect locomotor activity following METH injection (1mg/kg) suggesting that the observed effects of l-THP (2.50mg/kg) on METH-induced reinstatement were not due to motor impairments. Thus, l-THP (a natural, mixed dopamine (DA) receptor antagonist) attenuates METH self-administration and METH-induced reinstatement. PMID- 26806557 TI - Population pharmacokinetics of plasma-derived factor IX: procedures for dose individualization. AB - BACKGROUND: Population pharmacokinetic (POPPK) models describing factor IX (FIX) activity levels in plasma, in combination with individual FIX measurements, may be used to individualize dosing in the treatment of hemophilia B. OBJECTIVES: The aim was to reevaluate a previously developed POPPK model for FIX activity and to explore the number and timing of FIX samples required in pharmacokinetic (PK) dose individualization. METHODS: The POPPK model was reevaluated using an extended data set. Several sampling schedules, varying with respect to the timing and number of samples, were evaluated in a simulation study with relative dose errors compared between schedules. The performance of individually calculated doses was compared with commonly prescribed FIX doses with respect to the number of patients with a trough FIX activity > 0.01 U mL(-1) . RESULTS AND CONCLUSIONS: A three-compartment PK model best described the FIX activity levels. The number and timing of samples greatly influenced imprecision in dose prediction. Schedules with single samples taken on both day 2 and day 3 were identified as being convenient schedules with an acceptable performance level. Individually calculated doses performed better with respect to patient target attainment than a fixed 40 U kg(-1) dose regardless of how many samples were available to calculate individual doses. The results of this study suggest that PK dose tailoring with limited sampling may be applicable for plasma-derived FIX products. PMID- 26806559 TI - Electrolyte composition of retro-oil fluid and silicone oil-related visual loss. AB - PURPOSE: Up to one-third of patients with intra-ocular silicone oil (SO) tamponade for complex macula-on retinal detachment may experience an unexplained visual loss during or after SO tamponade. Although the underlying mechanism is unknown, previous studies suggested that accumulation of retinal potassium could be involved. Hence, this study tested the hypothesis that intra-ocular potassium levels are elevated during SO tamponade. METHODS: A prospective cohort study was carried out from 13 October 2013 through 5 March 2015. Potassium, sodium, magnesium, chloride, calcium, lactate dehydrogenase (LDH) and glucose levels were measured in retro-oil fluid and paired serum from 16 patients undergoing oil removal, including two patients with SO-related visual loss (SORVL). Vitreous humour and paired serum from 27 patients with macular hole (n = 19) or floaters (n = 8) served as controls. RESULTS: Median potassium levels in retro-oil fluid and vitreous humour were similar. Magnesium and chloride levels were lower in retro-oil fluid compared with vitreous humour (p < 0.01) and LDH levels were elevated in retro-oil fluid (p < 0.0001). One of the two patients with SORVL revealed abnormal high potassium and magnesium levels. The other patient had normal levels. CONCLUSION: Potassium levels are not increased in retro-oil fluid during SO tamponade, making the 'potassium accumulation' hypothesis unlikely. The disturbance in magnesium concentration during SO tamponade warrants further investigation. PMID- 26806558 TI - AMPK Suppresses Connexin43 Expression in the Bladder and Ameliorates Voiding Dysfunction in Cyclophosphamide-induced Mouse Cystitis. AB - Bladder voiding dysfunction is closely related to local oxidation, inflammation, and enhanced channel activities. Given that the AMP-activated protein kinase (AMPK) has anti-oxidative, anti-inflammatory and channel-inhibiting properties, we examined whether and how AMPK affected bladder activity. AMPK activation in rat bladder smooth muscle cells (BSMCs) using three different AMPK agonists resulted in a decrease in connexin43 (Cx43) expression and function, which was associated with reduced CREB phosphorylation, Cx43 promoter activity and mRNA expression, but not Cx43 degradation. Downregulation of CREB with siRNA increased Cx43 expression. A functional analysis revealed that AMPK weakened BSMC contraction and bladder capacity. AMPK also counteracted the IL-1beta- and TNFalpha-induced increase in Cx43 in BSMCs. In vivo administration of the AMPK agonist AICAR attenuated cyclophosphamide-initiated bladder oxidation, inflammation, Cx43 expression and voiding dysfunction. Further analysis comparing the responses of the wild-type (Cx43(+/+)) and heterozygous (Cx43(+/-)) Cx43 mice to cyclophosphamide revealed that the Cx43(+/-) mice retained a relatively normal micturition pattern compared to the Cx43(+/+) mice. Taken together, our results indicate that AMPK inhibits Cx43 in BSMCs and improves bladder activity under pathological conditions. We propose that strategies that target AMPK can be developed as novel therapeutic approaches for treating bladder dysfunction. PMID- 26806560 TI - Tobacco-specific N-nitrosamines NNN and NNK levels in cigarette brands between 2000 and 2014. AB - The evolution of the levels of tobacco-specific N-nitrosamines (TSNA), N nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in mainstream (MS) cigarette smoke is investigated based on smoke and tobacco chemistry data of cigarette brands sold by Philip Morris International (PMI) between 2000 and 2014. A total of 315 cigarette samples representing a wide range of product and design characteristics manufactured by PMI between 2008 and 2014 were analyzed and compared to a previously published dataset of PMI brands manufactured in 2000. The data indicate that there is a substantial reduction of NNN and NNK levels in tobacco fillers and MS cigarette smoke per mg of tar and per mg of nicotine using Health Canada Intense (HCI) machine-smoking regime. This observed reduction in NNN and NNK levels in MS cigarette smoke is also supported by the downward trend observed on NNN and NNK levels in USA flue-cured Virginia and Burley tobacco lots from 2000 to 2014 crops, reflecting effectiveness of measures taken on curing and agricultural practices designed to minimize TSNA formation in tobacco. PMID- 26806561 TI - Panel-based NGS Reveals Novel Pathogenic Mutations in Autosomal Recessive Retinitis Pigmentosa. AB - Retinitis pigmentosa (RP) is a group of inherited progressive retinal dystrophies (RD) characterized by photoreceptor degeneration. RP is highly heterogeneous both clinically and genetically, which complicates the identification of causative genes and mutations. Targeted next-generation sequencing (NGS) has been demonstrated to be an effective strategy for the detection of mutations in RP. In our study, an in-house gene panel comprising 75 known RP genes was used to analyze a cohort of 47 unrelated Spanish families pre-classified as autosomal recessive or isolated RP. Disease-causing mutations were found in 27 out of 47 cases achieving a mutation detection rate of 57.4%. In total, 33 pathogenic mutations were identified, 20 of which were novel mutations (60.6%). Furthermore, not only single nucleotide variations but also copy-number variations, including three large deletions in the USH2A and EYS genes, were identified. Finally seven out of 27 families, displaying mutations in the ABCA4, RP1, RP2 and USH2A genes, could be genetically or clinically reclassified. These results demonstrate the potential of our panel-based NGS strategy in RP diagnosis. PMID- 26806562 TI - Incorrect inference in prevalence trend analysis due to misuse of the odds ratio. AB - Because public health agencies usually monitor health outcomes over time for surveillance, program evaluation, and policy decisions, a correct health outcome trend analysis is vital. If the analysis is done incorrectly and/or results are misinterpreted, a faulty trend analysis could jeopardize key aspects of public health initiatives such as program planning, implementations, policy development, and clinical decision making. It is essential then that accurate health outcome trend analysis be implemented in any data-driven decision-making process. Unfortunately, there continues to be common statistical mistakes in prevalence trend analysis. In this article, using recently published results from the Pediatric Nutrition Surveillance System, we will show the effect that an incorrect trend analysis and subsequent interpretation of results can have. We will also propose more appropriate statistical processes, such as the log binomial model, for these situations. PMID- 26806563 TI - Recent advances in transition metal phosphide nanomaterials: synthesis and applications in hydrogen evolution reaction. AB - The urgent need of clean and renewable energy drives the exploration of effective strategies to produce molecular hydrogen. With the assistance of highly active non-noble metal electrocatalysts, electrolysis of water is becoming a promising candidate to generate pure hydrogen with low cost and high efficiency. Very recently, transition metal phosphides (TMPs) have been proven to be high performance catalysts with high activity, high stability, and nearly ~100% Faradic efficiency in not only strong acidic solutions, but also in strong alkaline and neutral media for electrochemical hydrogen evolution. In this tutorial review, an overview of recent development of TMP nanomaterials as catalysts for hydrogen generation with high activity and stability is presented. The effects of phosphorus (P) on HER activity, and their synthetic methods of TMPs are briefly discussed. Then we will demonstrate the specific strategies to further improve the catalytic efficiency and stability of TMPs by structural engineering. Making use of TMPs as cocatalysts and catalysts in photochemical and photoelectrochemical water splitting is also discussed. Finally, some key challenges and issues which should not be ignored during the rapid development of TMPs are pointed out. These strategies and challenges of TMPs are instructive for designing other high-performance non-noble metal catalysts. PMID- 26806564 TI - Feasible induction of coronary artery vasospasm occurred during cardiac catheterization in a microminipig. AB - A 14 month-old intact microminipig, weighing 8 kg, showed ST-segment elevation in A-B lead electrocardiogram during cardiac catheterization followed by ventricular tachycardia, which degenerated into ventricular fibrillation. Although a direct current defibrillation of 360 J was applied, ventricular tachycardia re-occurred for another 2 times and the direct defibrillation was repeated. After returning to normal sinus rhythm, a marked ST-segment elevation was still observed on leads II, III and aVF together with a remarkable decrease in contractility of inferior wall. The heart was excised for precise macroscopic and histological examinations, but there was no dissection, embolus or thrombus in the coronary arteries. These findings suggest that right coronary artery vasospasm could have caused the ischemic attack, leading to lethal arrhythmias. PMID- 26806565 TI - The Safety of Drug Therapy in Children. AB - BACKGROUND: 1.7% of children taking medication on an outpatient basis in Germany have at least one adverse drug reaction (ADR). The corresponding figure for hospitalized children is estimated at 10% . METHODS: This review is based on pertinent literature retrieved by a selective search in PubMed. RESULTS: According to reports submitted to the Drug Commission of the German Medical Association (Arzneimittelkommission der deutschen Arzteschaft, AkdA), serious ADRs can arise, for example, after the administration of dimenhydrinate, alpha adrenergic nose drops, enemas containing phosphate, ACE inhibitors, angiotensin-2 receptor antagonists (sartans), and methylphenidate. The causes of ADRs include overdoses, drug administration despite contraindications, and inadequate monitoring of long-term treatment. Errors can also be made in communication, labeling, and drug administration. The risk of ADRs is especially high in off label use. Computerized physician order entry systems, individual packaging and labeling of single doses, and the use of bar codes for patient and drug identification can help prevent such errors. CONCLUSION: The process of drug administration should be optimized through suitable interventions and electronic support, with due consideration of local circumstances. Clinical trials on children should be encouraged as a means of improving drug safety, and additional financial incentives should be created for trials concerning drugs that are off patent. Physicians and pharmacists should take care to report adverse reactions as they are required to do by professional code, particularly in the case of new drugs, off-label use, or medication errors. A recognized national standard for dosing that can be implemented in computerized physician order entry systems is needed so that evidence-based pediatric dosages can be calculated. PMID- 26806566 TI - Music Therapy in Palliative Care. AB - BACKGROUND: Music therapy has been used successfully for over 30 years as part of palliative care programs for severely ill patients. There is nonetheless a lack of high-quality studies that would enable an evidence-based evaluation of its psychological and physiological effects. METHODS: In a randomized controlled trial, 84 hospitalized patients in palliative care were assigned to one of two treatment arms--music therapy and control. The music therapy intervention consisted of two sessions of live music-based relaxation exercises; the patients in the control group listened to a verbal relaxation exercise. The primary endpoints were self-ratings of relaxation, well-being, and acute pain, assessed using visual analog scales. Heart rate variability and health-related quality of life were considered as secondary outcomes. The primary data analysis was performed according to the intention-to-treat principle. RESULTS: Analyses of covariance revealed that music therapy was more effective than the control treatment at promoting relaxation (F = 13.7; p <0.001) and well-being (F = 6.41; p = 0.01). This effect was supported by a significantly greater increase in high frequency oscillations of the heart rate (F = 8.13; p = 0.01). Music therapy did not differ from control treatment with respect to pain reduction (F = 0.4; p = 0.53), but it led to a significantly greater reduction in the fatigue score on the quality-of-life scale (F = 4.74; p = 0.03). CONCLUSION: Music therapy is an effective treatment with a low dropout rate for the promotion of relaxation and well-being in terminally ill persons undergoing palliative care. PMID- 26806568 TI - Metabolomics study on the effects of Buchang Naoxintong capsules for treating cerebral ischemia in rats using UPLC-Q/TOF-MS. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Buchang Naoxintong Capsules (BNC) are widely prescribed in Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases. However, the therapeutic effects and mechanisms are not yet well understood. MATERIALS AND METHODS: In this study, a UPLC/TOF-MS-based metabolomic study was conducted to explore potential biomarkers that will increase our understanding of cerebral ischemia and to assess the integral efficacy of BNC in a middle cerebral artery occlusion (MCAO) rat model. Plasma metabolic profiles were analyzed and metabolic biomarkers were identified through multivariate data analysis. RESULTS: Clear separations were observed between the sham, MCAO and BNC-treated groups. We identified 28 biomarkers in the MCAO rats using variable importance for the projections (VIP) values (VIP>1) and a t-test (P<0.05). The identified biomarkers were mainly related to disturbances in monoamine neurotransmitter metabolism, amino acid metabolism, energy metabolism and lipid metabolism. Moreover, a correlation network diagram of the plasma biomarkers perturbed by MCAO was constructed. Some biomarkers, such as glutamine, PE (17:0), LysoPE (20:1), LysoPE (24:0), and the ratios of LysoPE (24:1) to LysoPE (24:0), LysoPE (24:2) to LysoPE (24:0), showed obvious changes and a tendency for returning to baseline values in BNC-treated MCAO rats. In addition, MCAO rats receiving BNC treatment had improved neurological deficits and reduced cerebral infarct size demonstrating the therapeutic potential of BNC for treating cerebral ischemia. CONCLUSION: This study provides a useful approach for exploring the mechanism of MCAO-induced cerebral ischemia and evaluating the efficacy of BNC. PMID- 26806569 TI - Effects of Morus root bark extract and active constituents on blood lipids in hyperlipidemia rats. AB - OBJECTIVE: Chinese crude drug Mori Cortex Radicis (the root cortex of Morus species) has been used as a folk medicine to treat hypertension, diabetes, as well as in expectorant, diuretic agents. This investigation aims to study the anti-hyperlipidemia effects of Mori Cortex Radicis (MCR) extracts in hyperlipidemic rat models and the potential therapeutic activities of compounds isolated from the extracts. MATERIALS AND METHODS: The effects of MCR on hypolipidemic parameters were investigated using Wistar rats induced by high lipid emulsion. Sixty healthy Wistar rats were randomly divided into 6 groups: normal group, hyperlipidaemia model group, simvastatin, and high-, medium- and low-dose MCR extracts. After four weeks, body weight, total cholesterol (TC), triglycerides (TG), high and low-density lipoproteins (HDL, LDL), as well as aspartate aminotransferase (AST), alanine aminotransferase (ALT) were measured. To further investigation, four major active compounds were isolated from extracts through high performance liquid chromatography (HPLC) and their diacylglycerol acyltransferase 1 (DGAT1) inhibitory activity was evaluated. RESULTS: MCR dose dependently reduced serum TC, TG, LDL-C, inhibited the activity of ALT, AST, and increased HDL-C. Furthermore, in vitro biochemistry tests revealed that four active isolates showed moderate inhibitory activity against DGAT1 with IC50 values ranging from 62.1 +/- 1.2 to 99.3 +/- 2.3 uM. CONCLUSIONS: The results demonstrated that MCR could effectively ameliorate hyperlipidaemia and inhibit DGAT1 that a key enzyme closely related to hyperlipidaemia and type 2 diabetes. It may provide a new pharmacological basis for treating hyperlipidaemia and related diseases using MCR. PMID- 26806567 TI - Microglandular adenosis associated with triple-negative breast cancer is a neoplastic lesion of triple-negative phenotype harbouring TP53 somatic mutations. AB - Microglandular adenosis (MGA) is a rare proliferative lesion of the breast composed of small glands lacking myoepithelial cells and lined by S100-positive, oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2 negative epithelial cells. There is evidence to suggest that MGA may constitute a non-obligate precursor of triple-negative breast cancer (TNBC). We sought to define the genomic landscape of pure MGA and of MGA, atypical MGA (AMGA) and associated TNBCs, and to determine whether synchronous MGA, AMGA, and TNBCs would be clonally related. Two pure MGAs and eight cases of MGA and/or AMGA associated with in situ or invasive TNBC were collected, microdissected, and subjected to massively parallel sequencing targeting all coding regions of 236 genes recurrently mutated in breast cancer or related to DNA repair. Pure MGAs lacked clonal non-synonymous somatic mutations and displayed limited copy number alterations (CNAs); conversely, all MGAs (n = 7) and AMGAs (n = 3) associated with TNBC harboured at least one somatic non-synonymous mutation (range 3-14 and 1-10, respectively). In all cases where TNBCs were analyzed, identical TP53 mutations and similar patterns of gene CNAs were found in the MGA and/or AMGA and in the associated TNBC. In the MGA/AMGA associated with TNBC lacking TP53 mutations, somatic mutations affecting PI3K pathway-related genes (eg PTEN, PIK3CA, and INPP4B) and tyrosine kinase receptor signalling-related genes (eg ERBB3 and FGFR2) were identified. At diagnosis, MGAs associated with TNBC were found to display subclonal populations, and clonal shifts in the progression from MGA to AMGA and/or to TNBC were observed. Our results demonstrate the heterogeneity of MGAs, and that MGAs associated with TNBC, but not necessarily pure MGAs, are genetically advanced, clonal, and neoplastic lesions harbouring recurrent mutations in TP53 and/or other cancer genes, supporting the notion that a subset of MGAs and AMGAs may constitute non-obligate precursors of TNBCs. PMID- 26806570 TI - Improvement of the liver pathology by the aqueous extract and the n-butanol fraction of Sida pilosa Retz in Schistosoma mansoni-infected mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Sida pilosa Retz (Malvaceae) is a plant used in Africa for the treatment of intestinal helminthiasis, lower abdominal pains and dysmenorrhea. AIM OF THE STUDY: In order to determine the potential use of S. pilosa in the treatment of schistosomiasis mansoni, we evaluated the schistosomicidal, antioxidant and anti-fibrotic properties of the aqueous extract and the n-butanol fraction of its aerial parts. MATERIAL AND METHODS: S. pilosa aqueous extract (SpAE) at 100, 200 and 400mg/kg and n-butanol fraction (SpBF) at 50, 100 and 200mg/kg were administered per os to Schistosoma mansoni-infected mice for 4 weeks. Praziquantel (100mg/kg * 5 days) was used as reference drug. After sacrifice, worm burden and egg count, transaminases and proteins levels were evaluated. Malondialdehyde (MDA), lipid hydroperoxydes (LOOH), catalase (CAT), superoxide dismutase (SOD), eosinophil peroxidase (EPO) and myeloperoxidase (MPO) were also measured. The anti-fibrotic effect of the plant was evaluated by the determination of hydroxyproline and gamma-interferon (IFN gamma). RESULTS: The treatment of S. mansoni-infected mice by SpAE or SpBF resulted in a moderate reduction of worm burden and egg load in the liver and intestine. Both SpAE and SpBF significantly reversed the increasing liver proteins, MDA, LOOH and CAT levels induced by the infection. Moreover, SOD activity was improved by SpAE and SpBF. Schistosomiasis mansoni considerably increased the EPO (p<0.001) and MPO activities (p<0.001). SpAE treatment significantly reduced EPO and MPO activities at all doses. SpBF failed to reduce the increasing MPO and decreased EPO only at the highest dose. S. mansoni infection induced an increase in hydroxyproline content (p<0.001) and a decrease in IFN-gamma level (p<0.001). Both SpAE and SpBF significantly reduced hepatic hydroxyproline content, while only SpAE (p<0.05) improved IFN-gamma level. CONCLUSION: These results suggest that the liver pathology in schistosomiasis mansoni is improved by S. pilosa aqueous extract, which disclosed a moderate schistosomicidal, but strong antioxidant and anti-fibrotic activities. The n butanol fraction was however less active than the aqueous extract. PMID- 26806571 TI - The ethyl acetate fraction from Physalis alkekengi inhibits LPS-induced pro inflammatory mediators in BV2 cells and inflammatory pain in mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Physalis alkekengi is an edible herb whose fruit and calyx are traditionally used to treat a wide range of diseases including inflammation, toothache, and rheumatism. However, the effects of Physalis alkekengi fruit along with its calyx (PAF) on neuroinflammation and inflammatory pain behavior have not been reported yet. AIM OF THE STUDY: This study evaluated the anti-inflammatory effect of PAF on lipopolysaccharide (LPS)-induced neuroinflammation and several in vivo model of inflammatory pain in mice. MATERIALS AND METHODS: Here, first we studied the effects of PAF fractions on the production of pro-inflammatory mediators in LPS-treated BV2 microglial cells using enzyme-linked immunosorbent assay. The translocation of nuclear factor kappa B (NF-kappaB) and the involvements of Akt and mitogen-activated protein (MAP) kinases in ethyl acetate fraction of PAF (PAF-EA)-mediated anti inflammatory effect were measured using Western blotting. In in vivo experiments, the efficacy of PAF-EA was evaluated at the doses of 100 and 200mg/kg using several chemical-induced models of inflammatory pain such as acetic acid-induced writhing, formalin-induced paw licking and edema. RESULTS: We found that compared to other fractions, the PAF-EA more potently inhibited the LPS-induced generation of nitric oxide, tumor necrosis factor-alpha, interleukin-6 and reactive oxygen species. It also inhibited LPS-induced nuclear translocation of NF-kappaB. These actions of EA fraction were found to be associated with a disruption of Akt and MAP kinases signaling pathways. The EA fraction also significantly inhibited acetic acid-induced writhing, formalin-induced licking time and edema in mice. CONCLUSIONS: Our findings support the ethnopharmacological use of P. alkekengi fruit along with its calyx as an anti-inflammatory agent and suggest that the EA fraction of PAF may serve as a potential candidate to treat different neurological disorders and pain associated with inflammation. PMID- 26806572 TI - Amelioration of acute myocardial infarction by saponins from flower buds of Panax notoginseng via pro-angiogenesis and anti-apoptosis. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The root of Panax notoginseng is traditionally used as an anti-hemorrhagic agent to promote blood circulation without causing "congealed" blood. Furthermore, the flower of P. notoginseng is a popular, traditional medicine taken daily for the preventing of hypertension and for reducing blood cholesterol profiles. Besides, the flower of P. notoginseng contains a higher level of saponins, particularly protopanaxadiol-type ginsenosides, as compared to the root. However, detailed pharmacological studies on this flower have rarely been conducted. MATERIAL AND METHODS: In this study, the saponins extracted from the flower of P. notoginseng (FS) were examined on the endothelial cell migration assay, chemically induced vascular insufficiency model in zebrafish larvae and myocardial infraction (MI) model in rats, for determination of their pro-angiogenic and therapeutic effects on MI treatment. RESULTS: Our results demonstrate that FS significantly promoted VEGF-induced migration of human umbilical vein endothelial cells (HUVECs) and partially restored defective intersegmental vessels (ISV) in a chemically induced vascular insufficiency model of zebrafish larvae. When compared to MI group, two weeks post-treatment of FS (25-50mg/kg/day) induced approximately 3-fold upregulation of VEGF mRNA expression and a concomitant increase in blood vessel density in the peri-infarct area of the heart. Moreover, TUNEL analysis indicates a reduction in the mean apoptotic nuclei per field in peri-infarct myocardium upon FS treatment. CONCLUSIONS: The pro-angiogenic effects of FS demonstrated in in vitro and in vivo experimental models suggest that the purified saponin preparation from flowers of P. notoginseng may potentially provide preventive and therapeutic agent for cardiovascular diseases. PMID- 26806573 TI - Effects of salvianolic acid B and tanshinone IIA on the pharmacokinetics of losartan in rats by regulating the activities and expression of CYP3A4 and CYP2C9. AB - Losartan (LST) is a common chemical drug used to treat high blood pressure and reduce the risk of stroke in certain people with heart disease. Danshen, prepared from the dried root and rhizome of Salvia miltiorrhiza Bunge, has been widely used for prevention and treatment of various cardiovascular and cerebrovascular diseases. There are more than 35 formulations containing Danshen indexed in the 2010 Chinese Pharmacopoeia, which are often combined with LST to treat cardiovascular and cerebrovascular diseases in the clinic. The effects of the two major components of Danshen, salvianolic acid B (SA-B) and tanshinone IIA (Tan IIA), on the pharmacokinetics of losartan and its metabolite, EXP3174, in rats were investigated by liquid chromatography coupled with mass spectrometry (LC MS). Male Sprague-Dawley rats were randomly assigned to 3 groups: LST, LST+SA-B and LST+Tan IIA, and the main pharmacokinetic parameters were estimated after oral administration of LST, LST+SA-B and LST+Tan IIA. It was found that there are significant differences in the pharmacokinetic parameters among the three groups: Cmax, t1/2, AUC, AUMC in the LST+SA-B group was smaller than those in group LST, while larger in group LST+Tan IIA. Further, the effects of SA-B and Tan IIA on the metabolism of losartan was also investigated using rat liver microsomes in vitro. The results indicated that SA-B can induce the metabolism of LST, while Tan IIA can inhibit the metabolism of LST in rat liver microsomes in vitro by regulating activities of CYP450 enzymes. In addition, the effect of SA-B and Tan IIA on CYP3A4 and CYP2C9 expression was studied in Chang liver cells by western blotting and Real-time PCR. It was concluded that the two components of Danshen, SA-B and Tan IIA have different influences on the metabolism of LST: SA-B can obviously speed up the metabolism of LST by inducing CYP3A4/CYP2C9 activities and expression, however, Tan IIA can slow down the metabolism of LST by inhibiting CYP3A4/CYP2C9 activities. PMID- 26806574 TI - Aqueous extract from Aconitum carmichaelii Debeaux reduces liver injury in rats via regulation of HMGB1/TLR4/NF-KappaB/caspase-3 and PCNA signaling pathways. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii Debeaux is a well-known Chinese herb that has been used to treat liver diseases for many years in China. We investigated the effects of aqueous extract from Aconitum carmichaelii Debeaux (AEACD) on acute liver failure and identified the possible mechanisms of these effects. MATERIAL AND METHODS: Specific pathogen-free (SPF) male Wistar rats were used to establish acute liver failure model by intraperitoneal injection of D galactosamine (D-GalN) and treated with Stronger Neo-Minophagen C (SNMC) and AEACD by gavage. Then, the serum biochemical parameters, the pathological scores in the liver tissue, the mRNA expressions of toll- like receptor 4 (TLR4), nuclear factor kappa B (NF-kappaB), high mobility group box 1 (HMGB1) and caspase 3, the proliferating cell nuclear antigen (PCNA) positive rates were analyzed. RESULTS: The liver function was improved, the pathological scores were decreased, the expressions the TLR4, NF-kappaB, HMGB1, and caspase-3 were inhibited, and the PCNA positive rates were increased by both SNMC and AEACD, but AEACD induced greater effects. CONCLUSIONS: AEACD protected liver function by inhibiting inflammatory reaction, apoptosis and promoting liver tissue regeneration in the acute liver failure rats induced by D-galactosamine. PMID- 26806575 TI - Nauclea officinalis inhibits inflammation in LPS-mediated RAW 264.7 macrophages by suppressing the NF-kappaB signaling pathway. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Nauclea officinalis has been traditionally used in China for the treatment of fever, pneumonia and enteritidis etc. This study aims to investigate effects of N. officinalis on the inflammatory response as well as the possible molecular mechanism in LPS-stimulated RAW 264.7 murine macrophage cells. MATERIALS AND METHODS: Anti-inflammatory activity of N. officinalis (10, 20, 50, and 100ug/mL) was investigated by using LPS-induced RAW 264.7 macrophages. The NO production was determined by assaying nitrite in culture supernatants with the Griess reagent. The levels of TNF-alpha, IL-6 and IL-1beta in culture media were measured with ELISA kits. Real time fluorescence quantitative PCR was detected for mRNA expression of iNOS, TNF-alpha, IL-6 and IL 1beta. Western blot assay was performed to illustrate the inhibitory effects of N. officinalis on phosphorylation of IkappaB-alpha and NF-kappaB p65. RESULTS: Treatment with N. officinalis (10-100ug/mL) dose-dependently inhibited the production as well as mRNA expression of NO, TNF-alpha, IL-6 and IL-1beta in RAW 264.7 macrophages. Western blot assay suggested that the mechanism of the anti inflammatory effect was associated with the inhibition of phosphorylation of IkappaB-alpha and NF-kappaB p65. CONCLUSIONS: The results indicated that N. officinalis potentially inhibited the activation of upstream mediator NF-kappaB signaling pathway via suppressing phosphorylation of IkappaB-alpha and NF-kappaB p65 to inhibit LPS-stimulated inflammation. PMID- 26806576 TI - The pharmacokinetics and bioavailability of three canthinone alkaloids after administration of Kumu injection to rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Kumu injection (KMI) is made from the branches and stems of Picrasma quassiodes (D. Don) Benn. and has been used clinically for the treatment of upper respiratory tract infection, acute tonsillitis, enteritis and bacillary dysentery. 3-methylcanthin-2,6-dione, 5-hydroxy-4-methoxycanthin-6 one, 4,5-dimethoxycanthin-6-one are the active ingredients of KMI because of its therapeutic effects. AIM OF THE STUDY: To develop a LC-MS/MS method for simultaneous determination of three active canthinone alkaloids (4,5 dimethoxycanthin-6-one, 5-hydroxy-4-methoxycanthin-6-one and 3-methylcanthin-2,6 dione) in rat plasma and for the pharmacokinetic study of them after administered of KMI to rats. MATERIALS AND METHODS: Rats were divided into 5 groups (n=5 per group), 3 groups administered intramuscularly with a single dose of KMI at 0.30, 0.45 and 0.90mL/kg respectively, and the other 2 groups administered intragastically or intravenously a single dose of KMI at 0.9mL/kg respectively. The concentrations of 4,5-dimethoxycanthin-6-one, 5-hydroxy-4-methoxycanthin-6 one and 3-methylcanthin-2,6-dione in plasma were determined by the established LC MS/MS method at different time points and the pharmacokinetic parameters were estimated by non-compartmental analysis. RESULTS: Pharmacokinetic results indicated that all of the alkaloids were absorbed rapidly and 3-methylcanthin-2,6 dione was eliminated fastest in rats. After intramuscular administration of KMI to rats, the absolute bioavailability is excellent, and the pharmacokinetic profiles are characterized by the first order kinetics. CONCLUSION: The established method is suitable for the quantitation of the three alkaloids in rat plasma. And this pharmacokinetic study suggested that intramuscular injection of KMI was suitable in clinical usage. PMID- 26806577 TI - Effects of Shenfu injection on macrocirculation and microcirculation during cardiopulmonary resuscitation. AB - AIM OF THE STUDY: To examine the effects of Shenfu injection (SFI) on macrocirculation and microcirculation during ventricular fibrillation (VF) and cardiopulmonary resuscitation (CPR). MATERIALS AND METHODS: Sixteen female Landrace pigs were used in this study. After anesthesia, coronary perfusion pressure (CPP) was measured, and then the abdominal cavity was opened to observe the mesenteric microcirculation with the aid of sidestream dark field imaging. Following the guidelines, we determined microvascular flow index, perfused vessel density and proportion of perfused vessels both for large (diameter>20 MUm) and small (diameter<20 MUm) microvessels. SFI (1 ml/kg) or saline was given by vein injection at 1h before inducing VF. CPR was initiated after 4 min VF. RESULTS: The shocks and duration of CPR were less in the SFI group compared with saline group. As the occurrence of VF, the CPP suddenly dropped to near zero, and cannot be measured in the both groups. However, there was greater CPP during CPR and at 1h after return of spontaneous circulation in the SFI group than saline group. Compared with saline, SFI significantly improved the microcirculation parameters of large and small microvessels during VF and CPR. CONCLUSIONS: SFI can improve the microvascular blood flow and CPP during VF and CPR, and reduce the shocks and duration of CPR. PMID- 26806578 TI - Contact allergy to essential oils cannot always be predicted from allergy to fragrance markers in the baseline series. AB - BACKGROUND: Essential oils are fragrance substances that are labelled on cosmetic products by their INCI names, potentially confusing consumers. OBJECTIVES: To establish whether contact allergy to essential oils might be missed if not specifically tested for. METHODS: We tested 471 patients with 14 essential oils and 2104 patients with Melaleuca alternifolia oil between January 2008 and June 2014. All patients were tested with fragrance mix I, fragrance mix II, hydroxyisohexyl 3-cyclohexene carboxaldehyde, and Myroxylon pereirae. Three hundred and twenty-six patients were tested with hydroperoxides of limonene and linalool. RESULTS: Thirty-four patients had a +/++/+++ reaction to at least one essential oil. Eleven had no reaction to any of the six marker fragrance substances. Thus, 4 of 11 positive reactions to M. alternifolia oil, 2 of 7 reactions to Cymbopogon flexuosus oil, 1 of 5 reactions to Cananga odorata oil, 3 of 4 reactions to Santalum album oil and 2 of 3 reactions to Mentha piperita oil would have been missed without individual testing. CONCLUSION: A small number of patients who are allergic to essential oils could be missed if these are not specifically tested. Labelling by INCI names means that exposure may not be obvious. Careful inspection of so-called 'natural' products and targeted testing is recommended. PMID- 26806580 TI - Inflammatory markers associated with seizures. AB - Seizures can produce systemic changes, including elevated body temperature, white blood cell count, and C-reactive protein levels, which raises concern for potential infection. We describe seizure-induced inflammation-like responses and discuss how these changes may be distinguished from those associated with infection. We prospectively investigated 140 consecutive visits to the emergency room, in which patients presented with seizures. We defined elevated body temperature, white blood cell count, or C-reactive protein levels as inflammation like responses. We investigated the occurrence of inflammation-like responses, characteristics of the seizures, neurological status at the initial visit, outcomes, and clinical findings to determine the presence of infection. We ascertained whether the patients had infection or not based on the overall information post-discharge. An inflammation-like response was observed in 56.3% of all visits and 19.3% were diagnosed with concurrent infection. Among the visits with inflammation-like response, 34.7% were shown to have an infection. Increases in body temperature and C-reactive protein levels were milder (<39 degrees C and <6 mg/dl, respectively) in patients without infection compared to those with infection, whereas there was no difference in leukocytosis, with regard to the presence or absence of infection. Increased body temperature occurred only in cases of generalized tonic-clonic seizures, whereas leukocytosis and elevated C-reactive protein levels were reported in patients with any type of seizure. Body temperatures returned to normal within eight hours in uncomplicated cases. Seizures frequently induce an increase in body temperature, white blood cell count, or C-reactive protein levels, making it challenging to distinguish these changes from those associated with infection. Nonetheless, elevated body temperature in the absence of generalized tonic-clonic seizures, above 39C, or persisting for more than eight hours after recovery of consciousness, and C reactive protein levels above 6 mg/dl warrant close observation and consideration for concurrent infection. PMID- 26806581 TI - Impact of revascularization in patients with sustained ventricular arrhythmias, prior myocardial infarction, and preserved left ventricular ejection fraction. AB - BACKGROUND: The impact of revascularization on recurrent ventricular arrhythmias (VAs) in patients with coronary artery disease and relatively preserved left ventricular ejection fraction (LVEF) is unknown. OBJECTIVE: The purpose of this study was to determine the impact of revascularization on recurrent VAs or death. METHODS: A cohort study was conducted on consecutive patients with prior myocardial infarction and LVEF >=40% presenting with a first clinical sustained VA in the absence of an acute coronary syndrome. The impact of revascularization on recurrent VAs and all-cause mortality was assessed. RESULTS: A total of 274 patients (mean age 66.1 +/- 9.7 years, 85.4% male, mean LVEF 48.3% +/- 7.2%) were included in the study. Eight-eight patients (32.1%) underwent coronary revascularization. During mean follow-up of 6.2 +/- 5.1 years, 140 (51.1%) died or had recurrent sustained VAs or appropriate implantable-cardioverter defibrillator therapy. Revascularization was not associated with a significantly lower rate of recurrent VAs or death (multivariable hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.60-1.24, P = .43) regardless of whether it was complete or incomplete (HR 0.65, 95% CI 0.25-1.69, P = .37) or was performed by percutaneous or surgical means (HR 1.02, 95% CI 0.53-1.94, P = .96). An implantable-cardioverter defibrillator was associated with a significant reduction in mortality (HR 0.23, 95% CI 0.09-0.55, P = .001). CONCLUSION: Patients with prior myocardial infarction and LVEF >=40% who present with sustained VAs in the absence of an acute coronary syndrome remain at high risk for recurrent VAs and all-cause death. Coronary revascularization does not systemically mitigate this risk. PMID- 26806584 TI - Psychometric properties of the General Health Questionnaire-12 in a sample of Hong Kong employees. AB - The General Health Questionnaire-12 (GHQ-12) is a widely used instrument for measuring psychological strain, but the factor structure of the GHQ-12 is inconclusive. The present study examined one-factor, two- and three-factor models of the GHQ-12 using structural equations modelling in a longitudinal data-set of Hong Kong employees. The findings supported a two-factor model consisting of a 'Social Dysfunction' factor measured by three items, and an 'Anxiety/Depression' factor measured by four items. Implications and limitations are discussed. PMID- 26806582 TI - The need for and the challenges of measuring renal sympathetic nerve activity. AB - Renal denervation (RDN) was primarily developed to treat hypertension and is potentially a new method for treating arrhythmias. Because of the lack of a standardized protocol to measure renal sympathetic nerve activity, RDN is administered in a blind manner. This inability to assess efficacy at the time of treatment delivery may be a large contributor to the ambiguity of RDN outcomes reported in the hypertension literature. The advancement of RDN as a treatment of hypertension or arrhythmias will be hampered by the lack of delivery assessment, a deficiency that the cardiovascular electrophysiology community, with its expertise in recording and mapping, may have a role in addressing and overcoming. The development of endovascular recording of renal nerve action potentials may provide a useful accessory tool for RDN. Innovation in this area will be crucial as we as a community reconsider the therapeutic value of RDN. PMID- 26806585 TI - Proceedings from the Second Haploidentical Stem Cell Transplantation Symposium Haplo2014, San Francisco, California, December 4, 2014. AB - Significant progress has been made over the past decade in haploidentical transplantation, with the development of novel methods to control intense alloreactive reactions generated in the major HLA-mismatched setting. Application of post-transplantation cyclophosphamide has gained worldwide acceptance as an effective and low-cost way to perform this type of transplantation, with outcomes now similar to those from HLA-matched unrelated donors. These advances have resulted in improved treatment-related mortality, whereas disease relapse has emerged as the most common cause of treatment failure. In addition, improvements in immunologic reconstitution after transplantation are much needed, not only in haploidentical transplantation but in all forms of stem cell transplantation. This symposium has focused on some of the most promising methods to control alloreactivity in this form of transplantation and application of cellular therapy to prevent disease relapse after transplantation, as well as understanding immunologic reconstitution and foreseeable approaches to improve immune recovery after transplantation. PMID- 26806590 TI - Prevalence and Characteristics of the Maxillary C-shaped Molar. AB - INTRODUCTION: The anatomy of the maxillary C-shaped molar has been the subject of several case reports although no true prevalence research has ever been conducted. The aim of this observational study was to evaluate and characterize the incidence of these morphologies using cone-beam computed tomographic (CBCT) technology. METHODS: Patients having presurgical CBCT examination were selected. CBCT analysis was performed at 5 different axial levels, and the teeth were classified as maxillary molar C shapes according to the inclusion criteria for the present investigation. The prevalence of C-shaped anatomy was calculated. The z test for proportions in independent groups was used to analyze the differences between proportions. Intrarater reliability was also tested. RESULTS: A total of 2227 teeth (928 upper first molars and 1299 upper second molars) from 895 patients were included in this research. Five different types of C-shaped molars were found, which included fusion between mesiobuccal and palatal roots (type A), mesiobuccal and distobuccal roots (type B), distobuccal and palatal roots (type C), 2 possible palatal roots (type D), and mesiobuccal and palatal roots connecting with an independent distobuccal root canal at apical or between distobuccal and palatal roots connecting with an independent mesiobuccal root canal at apical (type E). The global prevalence was 1.1% for first molars and 3.8% for second molars. Differences were observed between sex, teeth, and some types of C shapes at P < .05. CONCLUSIONS: Maxillary C-shaped molars have low prevalence but high anatomic complexity. An understanding of their anatomic configuration and variations is important in ensuring that they are treated properly. Distinct differences exist between C-shaped configurations of upper and lower molars. PMID- 26806586 TI - Loss of T Follicular Helper Cells in the Peripheral Blood of Patients with Chronic Graft-versus-Host Disease. AB - B cell antihost antibody production plays a central role in chronic graft-versus host disease (cGVHD). T follicular helper (TFH) cells drive B cell responses and are implicated in this process. Given differences in cGVHD incidence between umbilical cord blood (UCB) and adult donor transplant recipients, we evaluated TFH cell reconstitution kinetics to define graft source differences and their potential pathogenic role in cGVHD. Although we observed significantly fewer TFH cells in the blood of UCB recipients (versus matched related donors [MRD]) early after transplantation, by 1 year the numbers of TFH cells were similar. Additionally, at both early (day 60) and late (1 year) time points, TFH cell phenotype was predominantly central memory cells in both cohorts. TFH cells were functional and able to produce multiple cytokines (INF-gamma, TNF-alpha, IL-2, IL 17, and IL-21) after stimulation. In contrast to mouse models, where an enhanced frequency of splenic TFH cells contributes to cGVHD, patients with cGVHD showed significantly depleted circulating TFH cells after both UCB and MRD transplantation. Low numbers of TFH cells early after UCB transplantation could directly contribute to less cGVHD in this cohort. Additionally, systemic therapy (including steroids and calcineurin inhibitors) may contribute to decreases in TFH cells in patients with cGVHD. These data provide further evidence supporting the importance of TFH cells in cGVHD pathogenesis. PMID- 26806591 TI - What is the Effect of No Endodontic Debridement on Postoperative Pain for Symptomatic Teeth with Pulpal Necrosis? AB - INTRODUCTION: Patients without a dentist or access to care may present to emergency rooms with pain. They are often prescribed medications until they can be treated. There are no studies to show if emergency endodontic debridement is better than giving medications during this symptomatic period. The purpose of this prospective, randomized study was to compare debridement versus no debridement on postoperative pain in emergency patients with symptomatic teeth, a pulpal diagnosis of necrosis, and a periapical radiolucency. METHODS: Ninety-five patients presenting with moderate to severe pain were analyzed. The patients were randomly divided into 2 groups: group 1 received anesthesia and endodontic debridement, and group 2 received anesthesia but no debridement. At the end of the appointment, all patients were given ibuprofen/acetaminophen. If needed, they could receive an escape medication. Patients received a 5-day diary to record their pain levels and medication taken. Success was defined as no or mild postoperative pain and no use of escape medication. Success data were analyzed using a logistic regression. RESULTS: Both groups had a decrease in postoperative pain and medication use over the 5 days. The debridement group had a significantly higher success rate than the no debridement group. There was no significant difference between the 2 groups with respect to escape drug use. CONCLUSIONS: Patients receiving debridement or no debridement had a decrease in postoperative pain over the 5 days. Debridement resulted in a statistically higher success rate, but there was no significant difference in the need for escape medication. PMID- 26806593 TI - Parasite biology: Virulence packages. PMID- 26806592 TI - Interactions between dietary oil treatments and genetic variants modulate fatty acid ethanolamides in plasma and body weight composition. AB - Fatty acid ethanolamides (FAE), a group of lipid mediators derived from long chain fatty acids (FA), mediate biological activities including activation of cannabinoid receptors, stimulation of fat oxidation and regulation of satiety. However, how circulating FAE levels are influenced by FA intake in humans remains unclear. The objective of the present study was to investigate the response of six major circulating FAE to various dietary oil treatments in a five-period, cross-over, randomised, double-blind, clinical study in volunteers with abdominal obesity. The treatment oils (60 g/12 552 kJ per d (60 g/3000 kcal per d)) provided for 30 d were as follows: conventional canola oil, high oleic canola oil, high oleic canola oil enriched with DHA, flax/safflower oil blend and corn/safflower oil blend. Two SNP associated with FAE degradation and synthesis were studied. Post-treatment results showed overall that plasma FAE levels were modulated by dietary FA and were positively correlated with corresponding plasma FA levels; minor allele (A) carriers of SNP rs324420 in gene fatty acid amide hydrolase produced higher circulating oleoylethanolamide (OEA) (P=0.0209) and docosahexaenoylethanolamide (DHEA) levels (P=0.0002). In addition, elevated plasma DHEA levels in response to DHA intake tended to be associated with lower plasma OEA levels and an increased gynoid fat mass. In summary, data suggest that the metabolic and physiological responses to dietary FA may be influenced via circulating FAE. Genetic analysis of rs324420 might help identify a sub population that appears to benefit from increased consumption of DHA and oleic acid. PMID- 26806594 TI - Bacterial genomics: Legionella's toolbox of effectors. PMID- 26806596 TI - Maternal positioning to correct occiput posterior fetal position during the first stage of labour: a randomised controlled trial. AB - OBJECTIVE: To evaluate the efficacy of the hands and knees position during the first stage of labour to facilitate the rotation of the fetal head to the occiput anterior position. DESIGN: Randomised controlled trial. SETTING: Geneva University Hospitals, Switzerland. POPULATION: A total of 439 women with a fetus in the occiput posterior position during the first stage of labour. METHODS: The women in the intervention group were invited to take a hands and knees position for at least for 10 minutes. Women allocated to the control group received the usual care. For both groups, 15 minutes after randomisation, women completed a short questionnaire to report their perceived pain and the comfort of their position. MAIN OUTCOME MEASURES: The rotation of the fetal head in occiput anterior position confirmed by ultrasonography 1 hour after randomisation. RESULTS: One hour after the randomisation, 35 of 203 (17%) fetuses were diagnosed as being in the occiput anterior position in the intervention group compared with 24 of 209 (12%) in the control group. This difference was not statistically significant (relative risk 1.50; 95% CI 0.93-2.43; P = 0.13). The change in the evaluation of comfort between the randomisation and 15 minutes after showed an improvement in 70 and 39 women, no change in 82 and 78 women and a decrease in 56 and 86 women in the intervention and control groups, respectively (P = 0.02). CONCLUSIONS: This study could not demonstrate a benefit of the hands and knees position to correct the occiput posterior position of the fetus during the first stage of labour, but the women reported an increase in their comfort level. TWEETABLE ABSTRACT: Hands and knees position does not facilitate rotation into occiput anterior but increases the comfort level of women. PMID- 26806597 TI - Severity of community acquired pneumonia in asthma patients. How and what are linked? PMID- 26806599 TI - Fundamentals and applications of self-assembled plasmonic nanoparticles at interfaces. AB - This tutorial review will introduce and explore fundamental and applied aspects of electrolytic interfaces incorporating nanoscale building blocks for use in novel applications such as sensors and tunable optics. In order to do this, it is important to understand the principles behind even the simplest of immiscible interfaces such as those of the liquid|liquid and solid|liquid. Qualitatively, the picture is simple however the complexity is easily compounded by the addition of electrolyte, and further compounded by the addition of more complex entities such as nanoparticles. Nevertheless combining all these components surprisingly results in an elegant solution, where the nanoparticles have the ability to self assemble at the interface with a high level of control. Importantly, this opens up the door to the development of new types of materials with a range of applications which have only recently been exploited. Initially we begin with a description of the fundamentals related to liquid|liquid and solid|liquid interfaces both with and without electrolyte. The discussion then shifts to a description of biasing the interface by the application of an electric field. This is followed by an exploration of nanoparticle assembly and disassembly at the interface by controlling parameters such as ligand composition, charge, pH, and electric field. Finally a description of the state-of-the-art is given in terms of current applications and possible future directions. It is perhaps fair to say that these new frontiers have caused great excitement within the sensing community not only due to the simplicity of the technique but also due to the unprecedented levels of sensitivity and control. PMID- 26806600 TI - Nursing Activity Score for estimating nursing care need in intensive care units: findings from a face and content validity study. AB - AIM: To re-evaluate the face and content validity of the Nursing Activity Score currently adopted in evaluating activities that best describe workloads in intensive care units and their weight in describing average nursing time consumption. BACKGROUND: The Nursing Activity Score calculates the amount of nursing time that each patient will require over the next 24 hours. It has been widely used around the world since its first validation in 2003. However, no re evaluation of its validity with regard to the advancements achieved in intensive care units nursing care has been documented to date. METHOD: A research project was undertaken from 2012 to 2015, aimed at critically evaluating and validating this tool in the current context of Italian intensive care units nursing care. The 23 items were translated forward and backward into the Italian language, then a panel of 10 experts in critical care evaluated the face validity. Content validity was evaluated through focus groups involving seven critical care expert registered nurses. FINDINGS: The Nursing Activity Score instrument has been considered as not fully adequate to measure current intensive care units nursing activities and their weightings have been considered not fully adequate to score average nursing time consumption. From the content validity process, lack of adequacy has emerged with respect to the concept of nursing care underpinning the tool, the interventions included, its capability to predict the nursing resources needed, advancements achieved in intensive care units nurses' roles and competences, and the contextual factors that may influence consumption of nursing time. CONCLUSIONS: Development of the Nursing Activity Score tool both conceptually and in its structure, in view of the innovations that have occurred in the context of intensive care units, is necessary to continue to have a common tool to help clinicians and managers to capture accurately and compare nursing care required by patients in critical care settings. IMPLICATIONS FOR NURSING MANAGEMENT: There is a need to revise the Nursing Activity Score tool, enabling its use in estimating nursing workloads in current Italian intensive care units practice. A taskforce of clinical nurses and nursing managers, capable of protecting the valuable original Nursing Activity Score project and to advance its further development is recommended. PMID- 26806595 TI - Within-host evolution of bacterial pathogens. AB - Whole-genome sequencing has opened the way for investigating the dynamics and genomic evolution of bacterial pathogens during the colonization and infection of humans. The application of this technology to the longitudinal study of adaptation in an infected host--in particular, the evolution of drug resistance and host adaptation in patients who are chronically infected with opportunistic pathogens--has revealed remarkable patterns of convergent evolution, suggestive of an inherent repeatability of evolution. In this Review, we describe how these studies have advanced our understanding of the mechanisms and principles of within-host genome evolution, and we consider the consequences of findings such as a potent adaptive potential for pathogenicity. Finally, we discuss the possibility that genomics may be used in the future to predict the clinical progression of bacterial infections and to suggest the best option for treatment. PMID- 26806601 TI - Motor delays in MDMA (ecstasy) exposed infants persist to 2 years. AB - BACKGROUND: Recreational use of 3,4 methylenedioxymethamphetamine (ecstasy, MDMA) is increasing worldwide. Its use by pregnant women causes concern due to potentially harmful effects on the developing fetus. MDMA, an indirect monoaminergic agonist and reuptake inhibitor, affects the serotonin and dopamine systems. Preclinical studies of fetal exposure demonstrate effects on learning, motor behavior, and memory. In the first human studies, we found prenatal MDMA exposure related to poorer motor development in the first year of life. In the present study we assessed the effects of prenatal exposure to MDMA on the trajectory of child development through 2 years of age. We hypothesized that exposure would be associated with poorer mental and motor outcomes. MATERIALS AND METHODS: The DAISY (Drugs and Infancy Study, 2003-2008) employed a prospective longitudinal cohort design to assess recreational drug use during pregnancy and child outcomes in the United Kingdom. Examiners masked to drug exposures followed infants from birth to 4, 12, 18, and 24 months of age. MDMA, cocaine, alcohol, tobacco, cannabis, and other drugs were quantified through a standardized clinical interview. The Bayley Scales (III) of Mental (MDI) and Motor (PDI) Development and the Behavior Rating Scales (BRS) were primary outcome measures. Statistical analyses included a repeated measures mixed model approach controlling for multiple confounders. RESULTS: Participants were pregnant women volunteers, primarily white, of middle class socioeconomic status, average IQ, with some college education, in stable partner relationships. Of 96 women enrolled, children of 93 had at least one follow-up assessment and 81 (87%) had >= two assessments. Heavier MDMA exposure (M=1.3+/-1.4 tablets per week) predicted lower PDI (p<.002), and poorer BRS motor quality from 4 to 24 months of age, but did not affect MDI, orientation, or emotional regulation. Children with heavier exposure were twice as likely to demonstrate poorer motor quality as lighter and non-exposed children (O.R.=2.2, 95%, CI=1.02-4.70, p<.05). DISCUSSION: Infants whose mothers reported heavier MDMA use during pregnancy had motor delays from 4 months to two years of age that were not attributable to other drug or lifestyle factors. Women of child bearing age should be cautioned about the use of MDMA and MDMA-exposed infants should be screened for motor delays and possible intervention. PMID- 26806602 TI - What are narratives good for? AB - Narratives may be easy to come by, but not everything is worth narrating. What merits a narrative? Here, I follow the lead of narratologists and literary theorists, and focus on one particular proposal concerning the elements of a story that make it narrative-worthy. These elements correspond to features of the natural world addressed by the historical sciences, where narratives figure so prominently. What matters is contingency. Narratives are especially good for representing contingency and accounting for contingent outcomes. This will be squared with a common view that narratives leave no room for chance. On the contrary, I will argue, tracing one path through a maze of alternative possibilities, and alluding to those possibilities along the way, is what a narrative does particularly well. PMID- 26806603 TI - Pharmacological treatment with mirtazapine rescues cortical atrophy and respiratory deficits in MeCP2 null mice. AB - Loss of MeCP2 (Methyl CpG binding protein 2) in Rett syndrome (RTT) causes brain weight decrease, shrinkage of the cortex with reduced dendritic arborization, behavioral abnormalities, seizures and cardio-respiratory complications. The observed monoamine neurotransmitters reduction in RTT suggested antidepressants as a possible therapy. We treated MeCP2-null mice from postnatal-day 28 for two weeks with desipramine, already tested in RTT, or mirtazapine, an antidepressant with limited side-effects, known to promote GABA release. Mirtazapine was more effective than desipramine in restoring somatosensory cortex thickness by fully rescuing pyramidal neurons dendritic arborization and spine density. Functionally, mirtazapine treatment normalized heart rate, breath rate, anxiety levels, and eliminated the hopping behavior observed in MeCP2-null mice, leading to improved phenotypic score. These morphological and functional effects of mirtazapine were accompanied by reestablishment of the GABAergic and glutamatergic receptor activity recorded in cortex and brainstem tissues. Thus, mirtazapine can represent a new potential pharmacological treatment for the Rett syndrome. PMID- 26806605 TI - Chronic subcutaneous brain natriuretic peptide therapy in asymptomatic systolic heart failure. AB - AIMS: We have previously reported that asymptomatic systolic heart failure (HF) is characterized by an impaired renal response to volume expansion due to lack of activation of urinary cGMP which is corrected by subcutaneous (SQ) BNP. In the current study, we sought to define the cardiorenal response to intravascular volume expansion after 12 weeks of SQ BNP therapy. METHODS AND RESULTS: We utilized a double-blinded, placebo-controlled study to compare 12 weeks of twice daily SQ BNP 10 ug/kg (n = 22) or placebo (n = 12) in asymptomatic systolic HF. Subjects underwent two study visits: baseline and after 12 weeks of therapy. At each study visit, echocardiography, renal, and neurohumoral assessments were performed before and after intravascular volume expansion. The primary endpoint was change in urinary sodium excretion in response to volume expansion at 12 weeks, and we observed a greater increase in urinary sodium excretion [166 (77, 290) vs. 15 (-39, 72) mEq/min; P = 0.02] with SQ BNP treatment vs. placebo. Secondary endpoints included change in urine flow and glomerular filtration rate (GFR) in response to volume expansion at 12 weeks. We observed a significant increase in urine flow (P < 0.01) and trend for differential response in GFR (P = 0.08) with SQ BNP treatment vs. placebo. CONCLUSION: Among patients with asymptomatic systolic HF, twice-daily SQ BNP therapy improved the cardiorenal response to volume expansion at 12-week follow-up. Further studies are warranted to determine if these beneficial physiological observations with chronic natriuretic peptide administration translate into a delay in the progression to symptomatic HF. PMID- 26806606 TI - Social and novel contexts modify hippocampal CA2 representations of space. AB - The hippocampus supports a cognitive map of space and is critical for encoding declarative memory (who, what, when and where). Recent studies have implicated hippocampal subfield CA2 in social and contextual memory but how it does so remains unknown. Here we find that in adult male rats, presentation of a social stimulus (novel or familiar rat) or a novel object induces global remapping of place fields in CA2 with no effect on neuronal firing rate or immediate early gene expression. This remapping did not occur in CA1, suggesting this effect is specific for CA2. Thus, modification of existing spatial representations might be a potential mechanism by which CA2 encodes social and novel contextual information. PMID- 26806607 TI - The tumour hypoxia induced non-coding transcriptome. AB - Recent investigations have highlighted the importance of the non-coding genome in regions of hypoxia in tumours. Such regions are frequently found in solid tumours, and are associated with worse patient survival and therapy resistance. Hypoxia stabilises the transcription factors, hypoxia inducible factors (HIF1alpha and HIF2alpha) which coordinate transcriptomic changes that occur in hypoxia. The changes in gene expression induced by HIF1alpha and HIF2alpha contribute to many of the hallmarks of cancer phenotypes and enable tumour growth, survival and invasion in the hypoxic tumour microenvironment. Non-coding RNAs, in particular microRNAs (miRNAs), which regulate mRNA stability and translation, and long-non-coding RNAs (lncRNAs), which have diverse functions including chromatin modification and transcriptional regulation, are also important in enabling the key hypoxia regulated processes. They have roles in the regulation of metabolism, angiogenesis, autophagy, invasion and metastasis in the hypoxic microenvironment. Furthermore, HIF1alpha and HIF2alpha expression and stabilisation are also regulated by both miRNAs and lncRNAs. Here we review the recent developments in the expression, regulation and functions of miRNAs, lncRNAs and other non-coding RNA classes in tumour hypoxia. PMID- 26806608 TI - Long-term Follow-up of Longitudinal Melanonychia in Children and Adolescents Using an Objective Discrimination Index. PMID- 26806609 TI - Challenge accepted: Confronting readmissions for our patients with cirrhosis. PMID- 26806610 TI - Influenza Virus Shedding in Laninamivir-Treated Children upon Returning to School. AB - The current School Health and Safety Act in Japan states that children with influenza infection should stay home until day 6(th) after symptoms onset. This was an amendment of a previous version recommending school return on day 3 after defervescence. Here, we investigated the duration of fever and virus shedding after laninamivir treatment in 7 children infected with influenza A(H3N2) virus and 21 children with influenza B virus in relation to the school return timing recommended by the School Health and Safety Act during the 2011-2012 influenza season. Nasal discharge was collected on the first, second, and third hospital visits and virus titers were assessed by virus culture and real-time PCR. Duration of fever after laninamivir treatment was 1 day longer for influenza B than for influenza A(H3N2). Virus detection rates with 50% tissue culture infectious dose and viral RNA were highest at the first visit and gradually decreased at subsequent visits. Virus positivity rates were detectable at the time of defervescence in less than half of the enrolled patients (14.3-42.9%). Virus shedding rates were similarly low (0.0-19.0%) on day 3 or later from defervescence and on day 6 or later from fever onset (school return dates per the old and current School Health and Safety Act) regardless of the influenza type. In conclusion, despite the higher efficacy of laninamivir against A(H3N2) viruses than B viruses, viral shedding is low after return to school for both types, regardless of the version of the School Health and Safety Act. PMID- 26806611 TI - Identification of Biomarkers by Proteomics for Prenatal Screening for Neural Tube Defects. AB - Neural tube defect (NTD) is a serious congenital defect, but current methods for identifying NTD are limited. We used proteomic analysis of maternal serum to identify NTD-specific proteins whose levels differed between women with NTD fetuses (n = 50) and those with healthy fetuses (n = 40). Three NTD-specific protein peaks (8,130.6, 15,941.7, and 3,960.3 m/z) were identified using MALDI TOF-mass spectrophotemetry, and were included in a diagnostic model developed using Biomarker Patterns software. The model used cut-offs for the relative intensity of the three peaks to indicate if a case had or did not have NTD. The model identified 48 of the 50 NTD cases and 36 of the 40 control cases correctly, resulting in the sensitivity of 96.0% (48/50) and the specificity of 90.0% (36/40). The diagnostic model was also tested on 105 clinical cases at high risk for NTD, as determined by having high alpha-fetoprotein levels, resulting in the sensitivity of 100% (101/101) and the specificity of 75.0% (3/4). Using the International Protein Index database, we identified proteins with a molecular mass of 8,130.6 Da as ADP-ribosylation factor 1 and a protein similar to cold agglutinin FS-1 antibody light-chain. The 15,941.7-Da peak corresponded to vitamin K3 protein, and the identity of the 3,960.3-Da protein was unclear. Thus, this study developed a diagnostic model consisting of the three peaks which may be indicators of NTD. This new assay may be at least as accurate for diagnosing NTD compared with the commonly used clinical test that assesses alpha-fetoprotein levels. PMID- 26806612 TI - Enhanced upconversion luminescence through core/shell structures and its application for detecting organic dyes in opaque fishes. AB - Here, we report the enhanced upconversion luminescence of NaLuF4:18%Yb(3+),2%Er(3+) through core/shell structures. Among NaYF4, NaGdF4, and NaLuF4 shells, the first one presents the highest efficiency. These upconversion fluorescent nanoprobes with an oleic acid/PEG hybrid ligand can efficiently capture Rhodamine B (RB) and sodium fluorescein (SF) in opaque fishes to present their residues in vivo through luminescence resonant energy transfer (LRET) processes. It can be confirmed based on LRET technology that no RB is absorbed by opaque fishes after incubating in the aqueous solution of 1 MUg ml(-1) RB for one day, while SF residue can be obviously detected after incubating in the aqueous solution of 1 MUg ml(-1) SF for one day. The merit of this LRET technology with the upconversion nanoparticle (UCNP) donor is ascribed to the deep penetration depth of the infrared pumping laser and high signal to noise ratio. PMID- 26806613 TI - DNA damage in dab (Limanda limanda) and haddock (Melanogrammus aeglefinus) from European seas. AB - Dab (Limanda limanda) and haddock (Melanogrammus aeglefinus) were collected from coastal and offshore locations in the Baltic (dab only), North Sea (haddock from one location only) and Iceland. Blood was analysed for DNA strand breaks using the comet assay and liver samples for DNA adduct concentrations. DNA strand breaks were at background levels in dab from the two Iceland locations and from the Dogger Bank. The highest levels were observed in dab from the Firth of Forth, Ekofisk and the German Bight. Hepatic DNA adducts in dab were highest at Ekofisk, in the Baltic and Dogger Bank, below detection limit in dab from Iceland and low in dab from the Firth of Forth and German Bight. There was large variation in DNA strand breaks between locations and individuals for haddock, particularly from Iceland. Adduct concentrations were elevated in haddock from both Iceland and the Firth of Forth. A general linear model (GLM) suggested that, in addition to location, the size of dab and its general condition contributed to explaining the observed variability in DNA strand breaks. A GLM for adducts in dab similarly allocated most of the variability to location, but with a possible contribution from CYP1A activity. There were no apparent differences between male and female dab for any of the methods. There was no obvious relationship between strand breaks and adducts in the same fish although dab from Ekofisk and Iceland had respectively high and low responses using both methods. The results from this large-scale study showed pollution-related genotoxicity for dab, that fish blood samples can be conserved prior to comet analyses and that there are clear species differences in genotoxic responses even when collected at the same location. PMID- 26806614 TI - Serum Metabolomic Profiling in a Rat Model Reveals Protective Function of Paeoniflorin Against ANIT Induced Cholestasis. AB - Cholestasis is a leading cause of hepatic accumulation of bile acids resulting in liver injury, fibrosis, and liver failure. Paeoniflorin displays bright prospects in liver protective effect. However, its molecular mechanism has not been well explored. This study was designed to assess the effects and possible mechanisms of paeoniflorin against alpha-naphthylisothiocyanate-induced liver injury. Ultraperformance liquid chromatography coupled with quadrupole time-of-flight combined with principle component analysis and partial least squares discriminant analysis were integrated to obtain differentiating metabolites for the pathways and clarify mechanisms of disease. The results indicated that paeoniflorin could remarkably downregulate serum biochemical indexes and alleviate the histological damage of liver tissue. Different expression of 14 metabolites demonstrated that paeoniflorin mainly regulated the dysfunctions of glycerophospholipid metabolism and primary bile acid biosynthesis. Moreover, several pathways such as arginine and proline metabolism, ether lipid metabolism, and arachidonic acid metabolism were also related to the efficacy. In conclusion, paeoniflorin has indicated favorable pharmacological effect on serum biochemical indexes and pathological observation on cholestatic model. And metabolomics is a promising approach to unraveling hepatoprotective effects by partially regulating the perturbed pathways, which provide insights into mechanisms of cholestasis. PMID- 26806617 TI - 2-Nitrobenzyl Borate Based Photolabile Linker for Breakable Polymer Vesicles. AB - Fluorescent photolabile groups undergoing convenient synthesis and fast cleavage are being explored because of their increasing utility in both synthetic and biological chemistry. Herein, a model photosensitive poly(ethylene glycol)-lipid of NP-B-PEG with a 2-nitrobenzyl 2-pyridinylmethyl borate hydrophobic tail is synthesized. The (1) H-NMR and absorption spectra analysis of NP-B-PEG upon 365 nm irradiation in water supports a rapid photocleavage of nitrobenzyl borate with the concomitant hydrolysis of 2-pyridinylmethyl borate. It is also shown that the borate tail hydrolyzes slowly in water. Fortunately, when the polymer aqueous solution is loaded with the hydrophobic doxorubicin (DOX), the borate hydrolysis can be much retarded. The phototriggered experiment shows a two-stage DOX release: first, the slow leakage as a result of the photocleavage of 2 nitrobenzyl borate before the vesicle disintegration; second, the quick DOX precipitation from the disintegrated vesicles induced by the speeding up hydrolysis of 2-pyridinylmethyl borate. PMID- 26806619 TI - Cell migration towards CXCL12 in leukemic cells compared to breast cancer cells. AB - Chemotaxis or directed cell migration is mediated by signalling events initiated by binding of chemokines to their cognate receptors and the activation of a complex signalling cascade. The molecular signalling pathways involved in cell migration are important to understand cancer cell metastasis. Therefore, we investigated the molecular mechanisms of CXCL12 induced cell migration and the importance of different signalling cascades that become activated by CXCR4 in leukemic cells versus breast cancer cells. We identified Src kinase as being essential for cell migration in both cancer types, with strong involvement of the Raf/MEK/ERK1/2 pathway. We did not detect any involvement of Ras or JAK2/STAT3 in CXCL12 induced migration in Jurkat cells. Preventing PKC activation with inhibitors does not affect migration in Jurkat cells at all, unlike in the adherent breast cancer cell line MCF-7 cells. However, in both cell lines, knock down of PKCalpha prevents migration towards CXCL12, whereas the expression of PKCzeta is less crucial for migration. PI3K activation is essential in both cell types, however LY294002 usage in MCF-7 cells does not block migration significantly. These results highlight the importance of verifying specific signalling pathways in different cell settings and with different approaches. PMID- 26806620 TI - Phosphodiesterase 4 in inflammatory diseases: Effects of apremilast in psoriatic blood and in dermal myofibroblasts through the PDE4/CD271 complex. AB - Phosphodiesterases 4 (PDE4) act as proinflammatory enzymes via degradation of cAMP, whereas PDE4 inhibitors play an anti-inflammatory role in vitro and in vivo. In particular, apremilast has been recently approved for the treatment of psoriasis and psoriatic arthritis. However, little is known on the expression pattern of PDE4 in psoriasis. We report that PDE4B and PDE4D mRNA are overexpressed in peripheral blood mononuclear cells (PBMC) from psoriasis, as compared with normal controls, while apremilast reduces PBMC production of a number of pro-inflammatory cytokines and increases the levels of anti inflammatory mediators. PDE4 expression is up-regulated in psoriatic dermis as compared with normal skin, with particular regard to fibroblasts. This is confirmed in vitro, where both dermal fibroblasts (DF) and, to a greater extent, myofibroblasts (DM) express all PDE4 isoforms at the mRNA and protein level. Because PDE4 interacts with the nerve growth factor (NGF) receptor CD271 in lung fibroblasts, we evaluated the relationship and function of PDE4 and CD271 in normal human skin fibroblasts. All PDE4 isoforms co-immunoprecipitate with CD271 in DM, while apremilast inhibits apoptosis induced by beta-amyloid, a CD271 ligand, in DM. Furthermore, apremilast significantly reduces NGF- and transforming growth factor-beta1 (TGF-beta1)-induced fibroblast migration, and inhibits DF differentiation into DM mediated by NGF or TGF-beta1. Finally, in DM, apremilast significantly reduces cAMP degradation induced by treatment with beta amyloid. Taken together, these results indicate that PDE4 play an important role in psoriasis. In addition, the study reveals that the PDE4/CD271 complex could be important in modulating fibroblast functions. PMID- 26806621 TI - Techniques: Wide of the mark. PMID- 26806625 TI - Neurological disorders: A second wave. PMID- 26806627 TI - The right time to learn: mechanisms and optimization of spaced learning. AB - For many types of learning, spaced training, which involves repeated long inter trial intervals, leads to more robust memory formation than does massed training, which involves short or no intervals. Several cognitive theories have been proposed to explain this superiority, but only recently have data begun to delineate the underlying cellular and molecular mechanisms of spaced training, and we review these theories and data here. Computational models of the implicated signalling cascades have predicted that spaced training with irregular inter-trial intervals can enhance learning. This strategy of using models to predict optimal spaced training protocols, combined with pharmacotherapy, suggests novel ways to rescue impaired synaptic plasticity and learning. PMID- 26806630 TI - Should I stop or should I go? The role of complexin in neurotransmitter release. AB - When it comes to fusion with the neuronal cell membrane, does a synaptic vesicle have a choice whether to stop or to go? Recent work suggests that complexin, a tiny protein found within the synaptic terminal, contributes to the mechanism through which this choice is made. How complexin plays this consulting part and which synaptic vesicle proteins it interacts with remain open questions. Indeed, studies in mice and flies have led to the proposal of different models of complexin function. We suggest that understanding the modular nature of complexin will help us to unpick its role in synaptic vesicle release. PMID- 26806631 TI - Are women benefiting from the Affordable Care Act? A real-world evaluation of the impact of the Affordable Care Act on out-of-pocket costs for contraceptives. AB - OBJECTIVES: The Affordable Care Act (ACA) mandated that, starting between August 1, 2012 and July 31, 2013, health plans cover most Food and Drug Administration (FDA)-approved contraceptive methods for women without cost sharing. This study examined the impact of the ACA on out-of-pocket expenses for contraceptives. STUDY DESIGN: Women (ages 15-44years) with claims for any contraceptives in years 2011, 2012 and 2013 were identified from the MarketScan Commercial database. The proportions of women using contraceptives [including permanent contraceptives (PCs) and non-PCs: oral contraceptives (OCs), injectables, patches, rings, implants and intrauterine devices (IUDs)] in study years were determined, as well as changes in out-of-pocket expenses for contraceptives during 2011-2013. Demographics, including age, U.S. geographic region of residence and health plan type, were also evaluated. RESULTS: The number of women identified with any contraceptive usage in 2011 was 2,447,316 (mean age: 27.6years), in 2012 was 2,515,296 (mean age: 27.4years) and in 2013 was 2,243,253 (mean age: 27.4years). In 2011, 2012 and 2013, the proportions of women with any contraceptive usage were 26.3%, 26.2% and 26.9%, respectively. Over the three study years, mean total out-of-pocket expenses for PCs and non-PCs decreased from $298 to $82 and from $94 to $30, respectively. For non-PCs, mean total out-of-pocket expenses for OCs and IUDs decreased from $86 to $26 and from $83 to $20. CONCLUSIONS: Implementation of the ACA has saved women a substantial amount in out-of-pocket expenses for contraceptives. IMPLICATIONS: Mean total out-of-pocket expenses for FDA-approved contraceptives decreased approximately 70% from 2011 to 2013. Implementation of the ACA has saved women a substantial amount in out-of-pocket expenses for contraceptives. Longer-term studies, including clinical outcomes, are warranted. PMID- 26806632 TI - Relationship between coumarin-induced hepatocellular toxicity and mitochondrial function in rats. AB - The manifestation of coumarin-induced hepatocellular toxicity may differ and depends on the frequency of administration to rats. A single coumarin dose induces hepatocellular necrosis while repeated doses induce only hepatocyte degeneration. However, the mechanism underlying these effects remains unclear. Therefore, we investigated the mechanism of coumarin-induced hepatotoxicity in rats. Coumarin was administered to male rats as a single dose or for 4 consecutive days, and samples were obtained 4 or 24 h after a single dose or 24 h after the repeated doses. A single coumarin dose significantly induced hepatocellular necrosis in rats; however, toxicity was attenuated after repeated dosing. With a single dose, hepatocellular necrosis was preceded by increased mitochondrial number and size and decreased mitochondrial function. An increased expression of granular cytochrome P450 (CYP) 2E1 protein was observed in the cytoplasm and mitochondria of coumarin-treated rats compared to the expression in the untreated controls. Nevertheless, repeated dosing showed mitochondrial function that was equivalent to that of the control while enlarged CYP2E1 protein droplets were distributed outside the mitochondria. These results suggest that mitochondrial function and CYP2E1 expression might be involved in coumarin induced hepatocellular toxicity in rats. A reduction in mitochondrial CYP2E1 might be implicated in the acquisition of coumarin resistance after repeated doses. PMID- 26806629 TI - Autoimmune synaptopathies. AB - Autoantibodies targeting proteins at the neuromuscular junction are known to cause several distinct myasthenic syndromes. Recently, autoantibodies targeting neurotransmitter receptors and associated proteins have also emerged as a cause of severe, but potentially treatable, diseases of the CNS. Here, we review the clinical evidence as well as in vitro and in vivo experimental evidence that autoantibodies account for myasthenic syndromes and autoimmune disorders of the CNS by disrupting the functional or structural integrity of synapses. Studying neurological and psychiatric diseases of autoimmune origin may provide new insights into the cellular and circuit mechanisms underlying a broad range of CNS disorders. PMID- 26806628 TI - Rediscovering area CA2: unique properties and functions. AB - Hippocampal area CA2 has several features that distinguish it from CA1 and CA3, including a unique gene expression profile, failure to display long-term potentiation and relative resistance to cell death. A recent increase in interest in the CA2 region, combined with the development of new methods to define and manipulate its neurons, has led to some exciting new discoveries on the properties of CA2 neurons and their role in behaviour. Here, we review these findings and call attention to the idea that the definition of area CA2 ought to be revised in light of gene expression data. PMID- 26806633 TI - The effect of a low iron diet and early life methylmercury exposure in Daphnia pulex. AB - Iron (Fe) deficiency increases risk for adverse health outcomes in humans; however little is known about the potential interaction with methylmercury (MeHg) exposure. Studies testing multiple stressor hypotheses are expensive and time consuming in mammalian model systems; therefore, determining relevance of alternative models is important. Daphnia pulex were fed standard or low-Fe diets of freshwater algae, Ankistrodesmus falcatus. MeHgCl (1600 ng/L) or vehicle was added to culture media for 24 h during early life, and the combinatorial effects of a low-Fe diet and MeHg exposure on lifespan, maturation time, and reproduction were evaluated. Lipid storage effects were measured using image analysis of Oil Red O staining and triacylglyceride quantification. Our results show a dose dependent reduction in lifespan in D. pulex fed low Fe diets. Lipid analysis suggests an interactive effect of diet and MeHg exposure, with MeHg exposure increasing lipid storage in D. pulex fed a low-Fe diet. These findings suggest the effects of dietary iron intake and early life MeHg exposure in D. pulex may be mediated by changes in energetics that result in differential lipid storage. Therefore, lipid storage in D. pulex may be a useful screen for detecting long term effects of multiple stressors early in life. PMID- 26806634 TI - Xenopus as a model system for studying pancreatic development and diabetes. AB - Diabetes is a chronic disease caused by the loss or dysfunction of the insulin producing beta-cells in the pancreas. To date, much of our knowledge about beta cells in humans comes from studying rare monogenic forms of diabetes. Importantly, the majority of mutations so far associated to monogenic diabetes are in genes that exert a regulatory role in pancreatic development and/or beta cell function. Thus, the identification and study of novel mutations open an unprecedented window into human pancreatic development. In this review, we summarize major advances in the genetic dissection of different types of monogenic diabetes and the insights gained from a developmental perspective. We highlight future challenges to bridge the gap between the fast accumulation of genetic data through next-generation sequencing and the need of functional insights into disease mechanisms. Lastly, we discuss the relevance and advantages of studying candidate gene variants in vivo using the Xenopus as model system. PMID- 26806635 TI - The X factor: X chromosome dosage compensation in the evolutionarily divergent monotremes and marsupials. AB - Marsupials and monotremes represent evolutionarily divergent lineages from the majority of extant mammals which are eutherian, or placental, mammals. Monotremes possess multiple X and Y chromosomes that appear to have arisen independently of eutherian and marsupial sex chromosomes. Dosage compensation of X-linked genes occurs in monotremes on a gene-by-gene basis, rather than through chromosome-wide silencing, as is the case in eutherians and marsupials. Specifically, studies in the platypus have shown that for any given X-linked gene, a specific proportion of nuclei within a cell population will silence one locus, with the percentage of cells undergoing inactivation at that locus being highly gene-specific. Hence, it is perhaps not surprising that the expression level of X-linked genes in female platypus is almost double that in males. This is in contrast to the situation in marsupials where one of the two X chromosomes is inactivated in females by the long non-coding RNA RSX, a functional analogue of the eutherian XIST. However, marsupial X chromosome inactivation differs from that seen in eutherians in that it is exclusively the paternal X chromosome that is silenced. In addition, marsupials appear to have globally upregulated X-linked gene expression in both sexes, thus balancing their expression levels with those of the autosomes, a process initially proposed by Ohno in 1967 as being a fundamental component of the X chromosome dosage compensation mechanism but which may not have evolved in eutherians. PMID- 26806636 TI - Becoming a crossover-competent DSB. AB - The proper execution of meiotic recombination (or crossing over) is essential for chromosome segregation during the first meiotic division, and thus this process is regulated by multiple, and often elaborate, mechanisms. Meiotic recombination begins with the programmed induction of DNA double-strand breaks (DSBs), of which only a subset are selected to be repaired into crossovers. This crossover selection process is carried out by a number of pro-crossover proteins that regulate the fashion in which DSBs are repaired. Here, we highlight recent studies regarding the process of DSB fate selection by a family of pro-crossover proteins known as the Zip-3 homologs. PMID- 26806637 TI - Molecular control of fission yeast cytokinesis. AB - Cytokinesis gives rise to two independent daughter cells at the end of the cell division cycle. The fission yeast Schizosaccharomyces pombe has emerged as one of the most powerful systems to understand how cytokinesis is controlled molecularly. Like in most eukaryotes, fission yeast cytokinesis depends on an acto-myosin based contractile ring that assembles at the division site under the control of spatial cues that integrate information on cell geometry and the position of the mitotic apparatus. Cytokinetic events are also tightly coordinated with nuclear division by the cell cycle machinery. These spatial and temporal regulations ensure an equal cleavage of the cytoplasm and an accurate segregation of the genetic material in daughter cells. Although this model system has specificities, the basic mechanisms of contractile ring assembly and function deciphered in fission yeast are highly valuable to understand how cytokinesis is controlled in other organisms that rely on a contractile ring for cell division. PMID- 26806638 TI - Prediction models in obstetrics: understanding the treatment paradox and potential solutions to the threat it poses. PMID- 26806639 TI - High prevalence of risky income generation among street-involved youth in a Canadian setting. AB - BACKGROUND: Previous research has found a range of barriers to mainstream employment among street-involved youth; however, less is known about the characteristics of street-involved youth who engage in risky income generation and the potential role of substance use in perpetuating engagement in these activities. METHODS: Data were collected between 2005 and 2012 from the At-Risk Youth Study (ARYS), which is a prospective cohort study of street-involved youth aged 14-26 in Vancouver, Canada. Generalized estimating equations were used to identify factors associated with risky quasi-legal and illegal income generation. Participants also reported their willingness to give up these sources of income if they were not using drugs. RESULTS: Among 1008 participants, 826 (82%) reported engaging in risky income generation activities during the study period. Factors associated with risky income generation included: homelessness, binge drug use, injection drug use, crack use, crystal methamphetamine, overdose, interactions with police, and experiencing violence; regular employment was negatively associated with this outcome (all p<0.05). Among those who reported risky income generation, 440 (53%) were willing to give up these income sources if they were not using drugs. CONCLUSION: Risky income generation was alarmingly prevalent in our sample, and associated with higher intensity drug use and other markers of vulnerability. The majority of participants (53%) reported willingness to give up their risky income sources if they were not using drugs; however, a substantial proportion of youth (47%) indicated that they would continue to engage in risk income generation regardless of their substance use suggesting that both substance use and economic insecurity likely perpetuate risky income generation among our sample. Findings highlight opportunities to reduce risky income generation by addressing problematic substance use through better access and engagement with evidence-based addiction treatment, and exploring, monitoring and evaluating innovative interventions to improve the overall economic security of street-involved youth. PMID- 26806640 TI - Producing alcohol and other drugs as a policy 'problem': A critical analysis of South Africa's 'National Drug Master Plan' (2013-2017). AB - BACKGROUND: The strong symbolic value of illicit drug use makes it a contested issue, which attracts mixed public opinion, intense media attention and close political scrutiny. This means that the formulation of plausible, authoritative policies governing illicit drugs must navigate fraught political terrain. In a country like South Africa with its long unique history of institutionalised oppression of the black majority, the issues confronting drug policy are particularly complex and the need for carefully formulated policy responses especially urgent. Yet despite this, the area of drug policy development in South Africa has received little scholarly attention to date. METHODS: This paper explores the complexities of policymaking in the South African context by drawing on feminist scholar Carol Bacchi's poststructuralist approach to policy analysis, which focuses on how policy helps to produce the problems it purports to solve. Taking as its empirical focus, South Africa's current drug policy, the third National Drug Master Plan (NDMP), 2013-2017, the paper analyses how the policy constitutes the 'problem of alcohol and other drugs' (AODs). RESULTS: We identify three central policy proposals through which specific problematisations emerge: (1) the proposal that drug use is a global issue requiring a coordinated policy response, (2) appeals to evidence-based policy proposals and (3) the proposal that AOD 'use' and 'abuse' be treated interchangeably. We suggest that these proposals reveal a tendency towards inflating the 'problem of AODs' and thus work to justify punitive policy measures. CONCLUSIONS: In an effort to explore the implications of particular problematisations for effecting social change, we clarify the ways in which the policy may work to undermine the interests of those it seeks to aid by reinforcing stigma and marginalisation. PMID- 26806644 TI - Selective hydrogenation of levulinic acid to gamma-valerolactone using in situ generated ruthenium nanoparticles derived from Ru-NHC complexes. AB - Hydrogenation of levulinic acid (LA) to gamma-valerolactone (GVL) was studied by using mono- and bidentate p-cymene ruthenium(ii) N-heterocyclic carbene (NHC) complexes as catalyst precursors. In water, all complexes were found to be reduced in situ to form ruthenium nanoparticles (RuNPs) with a high hydrogenation activity. In organic solvents, complexes with monodentate NHC ligands also formed nanoparticles, while complexes with bidentate ligands gave rise to stable homogeneous catalysts with moderate hydrogenation activities. PMID- 26806642 TI - Targeting and retention enhancement of quantum dots decorated with amino acids in an invertebrate model organism. AB - The use of quantum dots (QDs) in biological imaging applications and targeted drug delivery is expected to increase. However, the efficiency of QDs in drug targeting needs to be improved. Here, we show that amino acids linked to CdTe QDs significantly increased the targeted transfer efficiency and biological safety in the invertebrate model Bombyx mori. Compared with bare QDs530, the transfer efficiency of Ala- and Gly-conjugated QDs (QDs530-Ala and QDs530-Gly) in circulatory system increased by 2.6 +/- 0.3 and 1.5 +/- 0.3 times, and increased by 7.8 +/- 0.9 and 2.9 +/- 0.2 times in target tissue silk glands, respectively, after 24 h of QDs exposure. Meanwhile, the amount of conjugated QDs decreased by (68.4 +/- 4.4)% and (46.7 +/- 9.1)% in the non-target tissue fat body, and the speed at which they entered non-target circulating blood cells significantly decreased. The resultant QDs530-Ala revealed a better structural integrity in tissues and a longer retention time in hemolymph than that of QDs530 after exposure via the dorsal vessel. On the other hand, QDs530-Ala significantly reduced the toxicity to hemocytes, silk gland, and fat body, and reduced the amount of reactive oxygen species (ROS) in tissues. PMID- 26806645 TI - Backbone assignment for minimal protein amounts of low structural homogeneity in the absence of deuteration. AB - NMR characterization of many proteins is limited by low expression, hurdles for deuteration, and poor sample homogeneity. We introduce a set of high dimensionality proton-detected experiments developed for unambiguous resonance assignments of such proteins, which we could successfully apply to a 1 mg amount of non-deuterated Tau paired helical filaments. PMID- 26806646 TI - AST-to-platelet ratio index in non-invasive assessment of long-term graft fibrosis following pediatric liver transplantation. AB - Long-term graft fibrosis occurs in the majority of pediatric liver transplant recipients. Serial biopsies to monitor graft health are impractical and invasive. The APRI has been evaluated in pediatric liver disease, but not in the context of post-transplantation fibrosis. We aimed to investigate the validity of APRI as a predictor of long-term graft fibrosis in pediatric liver transplant recipients. This was a retrospective, observational study of a cohort of children who underwent liver transplantation at King's College Hospital between 1989 and 2003, with a relevant dataset available. Protocol liver biopsies were performed at 10 yr follow-up and fibrosis was graded using the Ishak scoring system, with S3-6 denoting "significant fibrosis." APRI was calculated concurrently with biopsy. A total of 39 asymptomatic patients (20 males; median age at transplant, 1.43 yr) underwent protocol liver biopsies at a median of 10.39 yr post-transplantation. APRI was associated with significant fibrosis (p = 0.012). AUROC for APRI as a predictor of significant fibrosis was 0.74 (p = 0.013). The optimal cutoff APRI value for significant fibrosis was 0.45 (sensitivity = 0.67; specificity = 0.79; PPV = 0.67; NPV = 0.79). APRI appears to be a useful non-invasive adjunct in the assessment of significant graft fibrosis in the long-term follow-up of pediatric liver transplant survivors. PMID- 26806647 TI - Thermo-sensitive complex micelles from sodium alginate-graft-poly(N isopropylacrylamide) for drug release. AB - Polymer micelles with environmentally sensitive properties have potential applications in biomedicine. In this paper, thermo-sensitive complex micelles assembled from biocompatible graft copolymers sodium alginate-graft-poly(N isopropylacrylamide) (SA-g-PNIPAM) and divalent metal ions were prepared for controlled drug release. The polymer micelles had core-corona structure, which was constituted by metal ions (Ba(2+), Zn(2+), Co(2+)) cross-linked sodium alginate as the core and thermo-sensitive PNIPAM chains as the corona. Formation of polymer micelles was determined by Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The polymer micelles were observed as regular spheres with good polydispersity and excellent performance on drug encapsulation and release ability. The cumulative release of 5-fluorouracil (5-FU) from micelles was controlled by pH, ionic strength or temperature of surroundings. The superior properties of sensitive polymer micelles induced by metal ions are expected to be utilized in controlled drug delivery systems. PMID- 26806648 TI - Extraction, characterization and antioxidant activities of polysaccharides of Chuanminshen violaceum. AB - A single factor experiment and Box-Behnken design were applied to optimize the microwave-assisted extraction (MAE) of Chuanminshen violaceum polysaccharides (CVPs). The CVPs yield was 34.59 +/- 0.51%, which was in accordance with the predicted value of 35.54%, under the following optimum conditions: microwave power of 466 W, extraction temperature of 64.5 degrees C, extraction time of 15 min, and water-raw material ratio of 40 mL/g. Two CVPs fractions (CVPs-I and CVPs II) were obtained via stepwise ethanol precipitation. CVPs-II was further purified using DEAE cellulose-52 chromatography to obtain the major fraction of CVPs-IIa. Fourier transform infrared spectroscopy (FTIR) and GC-MS analysis revealed that crude CVPs, CVPs-I, and CVPs-II were neutral polysaccharides and were mainly composed of glucose and galactose. The molecular weights of CVPs-I and CVPs-IIa were 233.69 and 11.02 kDa, respectively. Furthermore, all samples exhibited certain antioxidant activity or reducing power to scavenge the DPPH and ABTS radicals, among which CVPs-II was the strongest. In conclusion, MAE is an efficient method for extracting CVPs of C. violaceum, and this plant root has the potential to be explored as a source of natural antioxidants. PMID- 26806649 TI - Optimization of folic acid nano-emulsification and encapsulation by maltodextrin whey protein double emulsions. AB - Due to susceptibility of folic acid like many other vitamins to environmental and processing conditions, it is necessary to protect it by highly efficient methods such as micro/nano-encapsulation. Our aim was to prepare and optimize real water in oil nano-emulsions containing folic acid by a low energy (spontaneous) emulsification technique so that the final product could be encapsulated within maltodextrin-whey protein double emulsions. A non ionic surfactant (Span 80) was used for making nano-emulsions at three dispersed phase/surfactant ratios of 0.2, 0.6, and 1.0. Folic acid content was 1.0, 2.0, and 3.0mg/mL of dispersed phase by a volume fraction of 5.0, 8.5, and 12%. The final optimum nano-emulsion formulation with 12% dispersed phase, a water to surfactant ratio of 0.9 and folic acid content of 3mg/mL in dispersed phase was encapsulated within maltodextrin-whey protein double emulsions. It was found that the emulsification time for preparing nano-emulsions was between 4 to 16 h based on formulation variables. Droplet size decreased at higher surfactant contents and final nano emulsions had a droplet size<100 nm. Shear viscosity was higher for those formulations containing more surfactant. Our results revealed that spontaneous method could be used successfully for preparing stable W/O nano-emulsions containing folic acid. PMID- 26806651 TI - Unexpected role of linker position on ammonium gemini surfactant lyotropic gyroid phase stability. AB - Arising from the water-driven self-assembly of amphiphiles over generally narrow temperature and composition phase windows, aqueous lyotropic liquid crystal (LLC) network phases are useful in applications as therapeutic delivery vehicles and templates for mesoporous material syntheses. While a clear set of amphiphile design rules that enables access to these intricate three-dimensional structures has yet to emerge, recent work indicates that bis(ammonium), bis(phosphonium), and dicarboxylate gemini ("twin tail") surfactants enable enhanced access to LLC network phases such as the double gyroid (G). In order to better understand the scope of this amphiphile design strategy, we investigated the synthesis and aqueous LLC self-assembly behaviors of a homologous series of quaternary gemini bis(ammonium) dichloride surfactants, in which we varied the position of the hydrophobic linker that connects the constituent single tail surfactants. These experiments demonstrate that the position of the linker directly impacts the maximum counterion-headgroup hydration capacity and the extent of counterion headgroup association, all of which contribute to the aqueous lyotropic double gyroid network phase stability. Thus, judicious selection of the linker position in ionic gemini surfactants provides a new molecular design tool for manipulating LLC network phase stability. PMID- 26806650 TI - Carboxylesterase 2 prevents liver steatosis by modulating lipolysis, endoplasmic reticulum stress, and lipogenesis and is regulated by hepatocyte nuclear factor 4 alpha in mice. AB - Nonalcoholic fatty liver disease (NAFLD) is a common liver disease that ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). So far, the underlying mechanism remains poorly understood. Here, we show that hepatic carboxylesterase 2 (CES2) is markedly reduced in NASH patients, diabetic db/db mice, and high-fat diet (HFD)-fed mice. Restoration of hepatic CES2 expression in db/db or HFD-fed mice markedly ameliorates liver steatosis and insulin resistance. In contrast, knockdown of hepatic CES2 causes liver steatosis and damage in chow- or Western diet-fed C57BL/6 mice. Mechanistically, we demonstrate that CES2 has triglyceride hydrolase activity. As a result, gain of hepatic CES2 function increases fatty acid oxidation and inhibits lipogenesis, whereas loss of hepatic CES2 stimulates lipogenesis by inducing endoplasmic reticulum stress. We further show that loss of hepatic CES2 stimulates lipogenesis in a sterol regulatory element-binding protein 1 (SREBP-1)-dependent manner. Finally, we show that hepatocyte nuclear factor 4 alpha (HNF-4alpha) plays a key role in controlling hepatic CES2 expression in diabetes, obesity, or NASH. CONCLUSION: CES2 plays a protective role in development of NAFLD. Targeting the HNF 4alpha/CES2 pathway may be useful for treatment of NAFLD. (Hepatology 2016;63:1860-1874). PMID- 26806652 TI - Click-Crosslinked Injectable Gelatin Hydrogels. AB - Injectable gelatin hydrogels formed with bioorthogonal click chemistry (ClickGel) are cell-responsive ECM mimics for in vitro and in vivo biomaterials applications. Gelatin polymers with pendant norbornene (GelN) or tetrazine (GelT) groups can quickly and spontaneously crosslink upon mixing, allowing for high viability of encapsulated cells, establishment of 3D elongated cell morphologies, and biodegradation when injected in vivo. PMID- 26806653 TI - Hydroxy-Safflower Yellow A inhibits the TNFR1-Mediated Classical NF-kappaB Pathway by Inducing Shedding of TNFR1. AB - Hydroxy-safflower yellow A (HSYA) is the major active component of safflower, a traditional Asia herbal medicine well known for its cardiovascular protective activities. The purpose of this study was to investigate the effect of HSYA on TNF-alpha-induced inflammatory responses in arterial endothelial cells (AECs) and to explore the mechanisms involved. The results showed that HSYA suppressed the up-regulation of ICAM-1 expression in TNF-alpha-stimulated AECs in a dose dependent manner. High concentration (120 MUM) HSYA significantly inhibited the TNF-alpha-induced adhesion of RAW264.7 cells to AECs. HSYA blocked the TNFR1 mediated phosphorylation and degradation of IkappaBalpha and also prevented the nuclear translocation of NF-kappaB p65. Moreover, HSYA reduced the cell surface level of TNFR1 and increased the content of sTNFR1 in the culture media. TNF alpha processing inhibitor-0 (TAPI-0) prevented the HSYA inhibition of TNFR1 induced IkappaBalpha degradation, implying the occurrence of TNFR1 shedding. Furthermore, HSYA induced phosphorylation of TNF-alpha converting enzyme (TACE) at threonine 735, which is thought to be required for its activation. Conclusively, HSYA suppressed TNF-alpha-induced inflammatory responses in AECs, at least in part by inhibiting the TNFR1-mediated classical NF-kappaB pathway. TACE-mediated TNFR1 shedding can be involved in this effect. Our study provides new evidence for the antiinflammatory and anti-atherosclerotic effects of HSYA. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26806654 TI - Removal of extracellular Toxoplasma gondii tachyzoites from suspended cell culture. AB - Tachyzoites of Toxoplasma gondii, an obligate intracellular parasite, actively invade a broad spectrum of cell types. T. gondii infects leukocytes and spreads to distant organs such as the brain, lungs and muscles. However, the mechanism of T. gondii transmission from infected leukocytes to peripheral organs is unknown. To show the dynamics of infected leukocytes and intracellular parasites in vivo, previous studies have prepared T. gondii-infected leukocytes and injected them into circulation in experimental animals. However, when the infected leukocytes are prepared in vitro, some extracellular tachyzoites remain in the leukocyte cell culture because it is almost impossible to wash out these extracellular tachyzoites. These extracellular tachyzoites may distort experimental results. In this study, we report a method for removing extracellular tachyzoites from leukocyte culture suspension using antibody-conjugated magnetic beads. Using this method, extracellular tachyzoites in suspension cell culture can be effectively eliminated. PMID- 26806655 TI - Latest Evidence on the Use of Phosphodiesterase Type 5 Inhibitors for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia. AB - CONTEXT: Several preclinical reports, randomized controlled trials, systematic reviews, and posthoc analyses corroborate the role of phosphodiesterase type 5 inhibitors (PDE5-Is) in the treatment of men with lower urinary tract symptoms (LUTS) associated with benign prostatic enlargement (BPE). OBJECTIVE: Update of the latest evidence on the mechanisms of action, evaluate the current meta analyses, and emphasize the results of pooled data analyses of PDE5-Is in LUTS/BPE. EVIDENCE ACQUISITION: Literature analysis of basic researches on PDE5 Is, systematic literature search in PubMed and Scopus until May 2015 on reviews of trials on PDE5-Is, and collection of pooled data available on tadalafil 5mg. EVIDENCE SYNTHESIS: Latest evidences on the pathophysiology of LUTS/BPE has provided the rationale for use of PDE5-Is: (1) improvement of LUT oxygenation, (2) smooth muscle relaxation, (3) negative regulation of proliferation and transdifferentiation of LUT stroma, (4) reduction of bladder afferent nerve activity, and (5) down-regulation of prostate inflammation are the proven mechanisms of action of PDE5-Is. Data from eight systematic reviews demonstrated that PDE5-Is allow to improve LUTS (International Prostate Symptom Score mean difference vs placebo: 2.35-4.21) and erectile function (International Index of Erectile Function mean difference vs placebo: 2.25-5.66), with negligible change in flow rate (Qmax mean difference vs placebo: 0.01-1.43). Pooled data analyses revealed that tadalafil 5mg once daily allows the clinically-meaningful improvement of LUTS and nocturnal voiding frequency independent of both erectile dysfunction severity and improvement. CONCLUSIONS: PDE5-Is are safe and effective in improving both LUTS and erectile function in appropriately selected men with LUTS/BPE. Data on the reduction of disease progression, long-term outcomes, and cost-effectiveness analyses are still lacking. PATIENT SUMMARY: We reviewed recent literature on phosphodiesterase type 5 inhibitors in men with lower urinary tract symptoms associated with prostatic enlargement. We found evidence to confirm that phosphodiesterase type 5 inhibitors are a valid treatment option for men affected by bothersome urinary symptoms with or without erectile dysfunction. PMID- 26806657 TI - En Bloc Resection of Bladder Tumors: Ready for Prime Time? PMID- 26806659 TI - Association between eye position on brain scan and hospital mortality in acute intracerebral hemorrhage. AB - BACKGROUND AND PURPOSE: Conjugate eye deviation (CED) and horizontal skew deviation are often seen in patients with intracerebral hemorrhage (ICH), but its prognostic significance is unclear. In this study, the association between brain scan assessed eye position and hospital mortality in patients with supratentorial ICH was tested. METHODS: A retrospective analysis was performed in 316 patients with supratentorial ICH. Eye position was measured on first brain computed tomography or magnetic resonance imaging. Patients with CED, horizontal skew deviation or no deviation were distinguished. The association between eye position and hospital mortality was assessed using logistic regression analysis. RESULTS: Conjugate eye deviation was present in 96 (30.4%), skew deviation in 44 (13.9%) and no deviation in 176 (55.7%) patients. In patients with CED, 81.3% had an eye position to the ipsilateral side of the hemorrhage. In univariable regression analysis, skew deviation was associated with mortality (odds ratio 3.10, 95% confidence interval 1.57-6.11; P = 0.001). In multivariable regression analysis, adjusting for age, ICH volume, intraventricular extension and Glasgow Coma Scale, eye position was not independently associated with mortality. CONCLUSION: Horizontal skew eyes were found to be an unfavorable prognostic factor. However, this was not independent of other important predictors of ICH mortality and is most probably explained by its association with worse initial clinical presentation. PMID- 26806658 TI - Utilization of a Genomic Classifier for Prediction of Metastasis Following Salvage Radiation Therapy after Radical Prostatectomy. AB - BACKGROUND: Despite salvage radiation therapy (SRT) for recurrent prostate cancer (PCa) after radical prostatectomy (RP), some patients still progress to metastases. Identifying these men would allow them to undergo systemic therapy including testing novel therapies to reduce metastases risk. OBJECTIVE: To test whether the genomic classifier (GC) predicts development of metastatic disease. DESIGN, SETTING, AND PARTICIPANTS: Retrospective multi-center and multi-ethnic cohort study from two academic centers and one Veterans Affairs Medical Center in the United States involving 170 men receiving SRT for recurrent PCa post-RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time from SRT to development of metastatic disease tested using Cox regression, survival c-index, and decision curve analysis. Performance of GC was compared to the Cancer of the Prostate Risk Assessment Score and Briganti risk models based on these metrics. RESULTS AND LIMITATIONS: With a median 5.7 yr follow-up after SRT, 20 patients (12%) developed metastases. On multivariable analysis, for each 0.1 unit increase in GC (scaled from 0 to 1), the hazard ratio for metastasis was 1.58 (95% confidence interval 1.16-2.17; p=0.002). Adjusting for androgen deprivation therapy did not materially change the results. The c-index for GC was 0.85 (95% confidence interval 0.73-0.88) versus 0.63-0.65 for published clinico-pathologic risk models. The 5-yr cumulative incidence of metastasis post-SRT in patients with low, intermediate, and high GC scores was 2.7%, 8.4%, and 33.1%, respectively (p<0.001). CONCLUSIONS: While validation in larger, prospectively collected cohorts is required, these data suggest GC is a strong predictor of metastases among men receiving SRT for recurrent PCa post-RP, accurately identifying men who are excellent candidates for systemic therapy due to their very high-risk of metastases. PATIENT SUMMARY: Genomic classifier and two clinico-pathologic risk models were evaluated on their ability to predict metastases among men receiving salvage radiation therapy for recurrent prostate cancer. Genomic classifier was able to identify candidates for further therapies due to their very high-risk of metastases. PMID- 26806656 TI - The Potential of MicroRNAs as Prostate Cancer Biomarkers. AB - CONTEXT: Short noncoding RNAs known as microRNAs (miRNAs) control protein expression through the degradation of RNA or the inhibition of protein translation. The miRNAs influence a wide range of biologic processes and are often deregulated in cancer. This family of small RNAs constitutes potentially valuable markers for the diagnosis, prognosis, and therapeutic choices in prostate cancer (PCa) patients, as well as potential drugs (miRNA mimics) or drug targets (anti-miRNAs) in PCa management. OBJECTIVE: To review the currently available data on miRNAs as biomarkers in PCa and as possible tools for early detection and prognosis. EVIDENCE ACQUISITION: A systematic review was performed searching the PubMed database for articles in English using a combination of the following terms: microRNA, miRNA, cancer, prostate cancer, miRNA profiling, diagnosis, prognosis, therapy response, and predictive marker. EVIDENCE SYNTHESIS: We summarize the existing literature regarding the profiling of miRNA in PCa detection, prognosis, and response to therapy. The articles were reviewed with the main goal of finding a common recommendation that could be translated from bench to bedside in future clinical practice. CONCLUSIONS: The miRNAs are important regulators of biologic processes in PCa progression. A common expression profile characterizing each tumor subtype and stage has still not been identified for PCa, probably due to molecular heterogeneity as well as differences in study design and patient selection. Large-scale studies that should provide additional important information are still missing. Further studies, based on common clinical parameters and guidelines, are necessary to validate the translational potential of miRNAs in PCa clinical management. Such common signatures are promising in the field and emerge as potential biomarkers. PATIENT SUMMARY: The literature shows that microRNAs hold potential as novel biomarkers that could aid prostate cancer management, but additional studies with larger patient cohorts and common guidelines are necessary before clinical implementation. PMID- 26806661 TI - Occurrence and distribution of polycyclic aromatic hydrocarbons in mussels from the gulf of Naples, Tyrrhenian Sea, Italy. AB - To assess the potential impact of the industrial activity on food safety and risk for consumers, the aim of the study was to evaluate the levels of 14 polycyclic aromatic hydrocarbons (PAH) in 69 samples of wild and farm Mytilus galloprovincialis, collected in sites of coast of Gulf of Naples, Tyrrhenian Sea. All hydrocarbons were found in samples. Higher levels of pyrolytic PAHs were in wild than in farm mussels. Benzo(a)pyrene exceeded the Regulation (EC) n.835/11 levels of 1 MUg/kg in 15 samples (71.42%) of wild and 25 samples (65.79%) of farm mussels. System of sum of 4 hydrocarbons exceeded the law level in 15 samples (71.42%) of wild and 21 samples (55.26%) of farm mussels. Wild mussel levels showed a potential impact of pyrolytic sources of PAH on food safety. Occurrence of carcinogenic PAHs should be a cause for concern, in areas where the mussels are being farmed for human consumption. PMID- 26806660 TI - Trace metals in the surface sediments of the intertidal Jiaozhou Bay, China: Sources and contamination assessment. AB - The major (Al) and trace metal (Cu, Pb, Zn, Cr, Cd, and As) concentrations in 29 surface sediment samples from the intertidal Jiaozhou Bay (JZB) are evaluated to assess the contamination level. The results show that the overall sediment quality in the area has been obviously impacted by trace metal contamination. The geoaccumulation index and the enrichment factor values indicate that no Cr or Cu contamination has occurred on the whole, only a few stations have been polluted by As, and some areas have been polluted by Cd, Pb, and Zn. Principal component analysis suggests that the Cu, Pb, Zn, and Cd are derived from anthropogenic inputs and that Cr, As, Cu, and Zn are influenced by natural weathering processes. Cu and Zn may originate from both natural and anthropogenic sources. The contamination in the northeastern JZB is higher than that in other areas of the bay. PMID- 26806662 TI - Distribution and sources of polycyclic aromatic hydrocarbons in surface sediments from the Bering Sea and western Arctic Ocean. AB - To analyze the distribution and sources of polycyclic aromatic hydrocarbons (PAHs) and evaluate their potential ecological risks, the concentrations of 16 PAHs were measured in 43 surface sediment samples from the Bering Sea and western Arctic Ocean. Total PAH (tPAH) concentrations ranged from 36.95 to 150.21 ng/g (dry weight). In descending order, the surface sediment tPAH concentrations were as follows: Canada Basin>northern Chukchi Sea>Chukchi Basin>southern Chukchi Sea>Aleutian Basin>Makarov Basin>Bering Sea shelf. The Bering Sea and western Arctic Ocean mainly received PAHs of pyrogenic origin due to pollution caused by the incomplete combustion of fossil fuels. The concentrations of PAHs in the sediments of the study areas did not exceed effects range low (ERL) values. PMID- 26806663 TI - WITHDRAWN: First record and distribution of the black pygmy mussel, Limnoperna securis (Lamarck, 1819) in the eastern Adriatic and Ionian seas. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 26806664 TI - A Model Longitudinal Observation Medicine Curriculum for an Emergency Medicine Residency. AB - The role of observation services for emergency department patients has increased in recent years. Driven by changing health care practices and evolving payer policies, many hospitals in the United States currently have or are developing an observation unit (OU) and emergency physicians are most often expected to manage patients in this setting. Yet, few residency programs dedicate a portion of their clinical curriculum to observation medicine. This knowledge set should be integrated into the core training curriculum of emergency physicians. Presented here is a model observation medicine longitudinal training curriculum, which can be integrated into an emergency medicine (EM) residency. It was developed by a consensus of content experts representing the observation medicine interest group and observation medicine section, respectively, from EM's two major specialty societies: the Society for Academic Emergency Medicine (SAEM) and the American College of Emergency Physicians (ACEP). The curriculum consists of didactic, clinical, and self-directed elements. It is longitudinal, with learning objectives for each year of training, focusing initially on the basic principles of observation medicine and appropriate observation patient selection; moving to the management of various observation appropriate conditions; and then incorporating further concepts of OU management, billing, and administration. This curriculum is flexible and designed to be used in both academic and community EM training programs within the United States. Additionally, scholarly opportunities, such as elective rotations and fellowship training, are explored. PMID- 26806665 TI - Iris cavernous haemangioma associated with recurrent hyphaema treated by laser photocoagulation. PMID- 26806666 TI - Retraction notice to "Protein dynamics by neutron scattering" [Biophysical Chemistry 182 (2013) 16-22]. PMID- 26806667 TI - Latent polyglandular autoimmune syndrome type 2 case diagnosed during a shock manifestation. AB - There are many types of polyglandular autoimmune syndrome (PAS). PAS type 2 is the most common type among adults. For PAS type 2 (PAS-2) diagnosis, detection of Addison's disease with autoimmune thyroid disease and/or type 1 diabetes mellitus are required. Premature ovarian insufficiency, pernicious anemia, vitiligo, alopecia, myasthenia gravis, celiac disease and autoimmune diabetes insipidus may be comorbidities of this condition. Contrary to the common belief, latent PAS is more common than the manifest forms. Here, we present a PAS-2 case diagnosed via adrenal crisis. At the time of diagnosis, the case was observed to have thyroid, adrenal and ovarian involvement. Therefore, PAS-2 and possible immunologic disorders were discussed. PMID- 26806668 TI - Lessons learned from a clinical trial: Design, rationale, and insights from The Cardiovascular Improvements with Minute Ventilation-targeted Adaptive Sero Ventilation (ASV) Therapy in Heart Failure (CAT-HF) Study. AB - OBJECTIVE: The CAT-HF Study was designed to evaluate the safety and efficacy of minute ventilation-targeted adaptive servo-ventilation (MV-ASV) during sleep in addition to optimized medical therapy (active therapy) versus optimized medical therapy alone (usual care) at 6 months, initiated in patients after hospitalization for acute decompensated heart failure (ADHF). This paper outlines the rationale, design and information learned at the time of study discontinuation. BACKGROUND: Sleep disordered breathing (SDB) is common in heart failure patients and is associated with worse outcomes in this patient population. Based on a belief that MV-ASV was safe in stable HF patients, CAT-HF was designed to examine whether MV-ASV improved outcomes in hospitalized HF patients During the course of CAT-HF, new results from SERVE-HF indicated that ASV therapy may be harmful in patients with left ventricular ejection fractions (LVEF)<=45% and central sleep apnea, a subgroup of patients enrolled in CAT-HF. METHODS: CAT-HF was a prospective, randomized, controlled, multicenter clinical trial (NCT: 01953874) in HF patients with either reduced or preserved ejection fraction and an Apnea-Hypopnea Index >=15 events per hour randomized to usual care or active treatment in a 1:1 ratio. 215 patients were intended to be randomized following a hospitalization for ADHF. At the time of discontinuation, 126 patients were randomized. The primary endpoint is a global rank composite endpoint of death, CV hospitalizations, and Six minute walk distance (6MWD). Secondary endpoints will include changes in functional parameters, biomarkers, quality of life (QOL), sleep, and breathing. CONCLUSIONS: The CAT-HF study was designed to assess the efficacy and safety of MV ASV treatment in patients after hospitalization for ADHF, but was stopped early due to safety concerns in HF patients with (LVEF)<=45% and predominant central sleep apnea. PMID- 26806669 TI - Measuring free-living physical activity in COPD patients: Deriving methodology standards for clinical trials through a review of research studies. AB - This article presents a review of the research literature to identify the methodology used and outcome measures derived in the use of accelerometers to measure free-living activity in patients with COPD. Using this and existing empirical validity evidence we further identify standards for use, and recommended clinical outcome measures from continuous accelerometer data to describe pertinent measures of sedentary behaviour and physical activity in this and similar patient populations. We provide measures of the strength of evidence to support our recommendations and identify areas requiring continued research. Our findings support the use of accelerometry in clinical trials to understand and measure treatment-related changes in free-living physical activity and sedentary behaviour in patient populations with limited activity. PMID- 26806670 TI - Rana grylio virus TK and DUT gene locus could be simultaneously used for foreign gene expression. AB - Ranaviruses (family Iridoviridae, genus Ranavirus) have been recognized as emerging infectious pathogens and caused a great loss to the global biodiversity. Thymidine kinase (TK) and deoxyuridine triphosphatase (dUTPase, DUT, encoded by ORF 67R) are ubiquitous, existing in iridoviruses and other organisms. Previous studies showed that TK and DUT could be individually knocked out without impeding viral replication. In this study, we tried to insert two fluorescence genes into the above loci. We started with Delta67R-RGV, a recently generated recombinant Rana grylio virus (RGV) with the whole DUT replaced by enhanced green fluorescence protein (EGFP) gene. Then, a red fluorescence protein (RFP) gene initiated by RGV immediate-early (IE) ICP18 gene promoter was inserted into TK locus through homologous recombination. A novel recombinant virus, DeltaDUT, TK RGV, was generated by nine successive rounds of plaque isolation using RFP selection. All of the plaques produced by this recombinant virus could emit both green and red fluorescence. Furthermore, one-step and multiple-step growth curves of DeltaDUT, TK-RGV were similar to those of wt-RGV and Delta67R-RGV. In conclusion, a novel dual-fluorescence labeled recombinant iridovirus in which DUT and TK gene locus were simultaneously used for foreign gene expression was constructed. PMID- 26806671 TI - Prediction of radiation-induced toxicity by in vitro radiosensitivity of lymphocytes in prostate cancer patients. AB - AIM: To identify predictive assays for radiation-induced toxicity in prostate cancer patients. PATIENTS & METHODS: Patients have been surveyed prospectively before and up to 16 months after radiotherapy using a validated questionnaire. Subgroups of 25 patients with minor and larger score changes, respectively, were selected for gamma-H2AX, G2 and Annexin V assays. RESULTS: A significantly higher spontaneous chromatid aberration yield (HR: 1.46 [95% CI: 1.02-2.09]; p = 0.04), higher levels of early apoptotic (HR: 1.12 [95% CI: 1.01-1.24]; p = 0.04) and late apoptotic and necrotic (HR: 1.10 [95% CI: 0.99-1.23]; p = 0.08) lymphocytes 24 h post-irradiation were found in patients with a bowel bother score decrease greater than 20 points more than 1 year after treatment. CONCLUSION: Chromatid aberration and apoptosis/necrosis assays appear to be suitable for the prediction of radiation-induced toxicity. PMID- 26806673 TI - Layering effects on low frequency modes in n-layered MX2 transition metal dichalcogenides. AB - n-Layered (n = 2, 3, 4) MX2 transition metal dichalcogenides (M = Mo, W; X = S, Se, Te) have been studied using DFT techniques. Long-range van der Waals forces have been modeled using the Grimme correction to capture interlayer interactions. We study the dynamic and electronic dependence of atomic displacement on the number of layers. We find that the displacement patterns mainly affected by a change in the layer number are low-frequency modes at Gamma and A k-points; such modes are connected with the intrinsic tribological response. We disentangle electro-phonon coupling by combining orbital polarization, covalency and cophonicity analysis with phonon band calculations. We find that the frequency dependence on the number of layers and the atomic type has a non-trivial relation with the electronic charge distribution in the interlayer region. We show that the interlayer electronic density can be adjusted by appropriately tuning M-X cophonicity, acting as a knob to control vibrational frequencies, hence the intrinsic frictional response. The present results can be exploited to study the electro-phonon coupling effects in TMD-based materials beyond tribological applications. PMID- 26806675 TI - [New therapies for cystic fibrosis targeting the CFTR gene or the CFTR protein]. AB - BACKGROUND: The treatment of cystic fibrosis has been symptom-based for a number of years. New therapies that aim to improve CFTR protein function are now emerging. CURRENT SCIENTIFIC KNOWLEDGE: The results of gene therapy has been modest but a recent clinical trial shows a positive effect on FEV1. Recent research has focused primarily on CFTR protein function. Significant respiratory improvement (an average 10% FEV1 increase and a decrease in the frequency of exacerbations) has been achieved with ivacaftor, a CFTR potentiator, in patients with gating mutations, resulting in its marketing authorization (in 2012 for the G551D mutation and in 2015 for rarer mutations). In phe508del homozygous patients, the combination of ivacaftor with a CFTR corrector (lumacaftor) has also led to respiratory improvement, albeit less impressive. The effectiveness of ataluren in patients with nonsense mutations is being evaluated. OUTLOOK: New CFTR correctors and potentiators are being developed. CFTR protein therapy could change the course of the disease but cost/effectiveness issues should not be overlooked. CONCLUSION: Ivacaftor can be prescribed in CF patients with a class 3 mutation from the age of 6 years. The Orkambi(r) will soon be available for homozygous phe508del patients from the age of 12 years. PMID- 26806676 TI - High cost pool or high cost groups-How to handle high(est) cost cases in a risk adjustment mechanism? AB - Competitive social health insurance systems (at least) in Western Europe have implemented systems of morbidity based risk adjustment to set a level playing field for insurers. However, many high cost insured still are heavily underfunded despite risk adjustment, leaving incentives for risk selection. In most of these health care systems, there is an ongoing debate about how to deal with such underpaid high cost cases. This study develops four distinct concepts by adding variables to risk adjustment or by setting up a high cost pool for underpaid insured besides the risk adjustment system. Their features, incentives and distributional effects are discussed. With a data set of 6 million insured, performance is demonstrated for Germany. All models achieve a substantial improvement in model fit, measured in terms of R(2) as well as CPM. As the results of the various models are different in different dimensions, the trade offs that have to be dealt with and should be addressed, when implementing a model to reduce underfunding of high cost cases. PMID- 26806677 TI - Influenza vaccination policy-making processes in France and The Netherlands: Framework and determinants. AB - OBJECTIVES: Target groups for seasonal influenza vaccination are nationally defined based on several factors. However, few studies have explored the policy making processes at the country-level. We investigated key differences in the policy-making process for the development of vaccination recommendations between France (FR) and The Netherlands (NL). This paper presents preliminary results on the evidence used in the decision-making process and focuses on the interactions between the experts and stakeholders. METHODS: A documentary analysis identified the stakeholders of this process as governmental authorities, research institutions, associations, and manufacturers. This qualitative study included at least one expert from each stakeholder group. Thirty-three semi-structured interviews were performed in 2013 (16 FR, 17 NL). We used NVivo10(r) to perform a thematic content analysis on the data. RESULTS: National Immunization Technical Advisory Groups (NITAGs) were the key stakeholders in the development of recommendations. There was no systematic standard evaluation of evidence during the decision-making process in both countries. Likewise, voting was not systematic, although it did occur more often in FR. A declaration of interests was obligatory in both countries. Experts with no conflicts of interest were rare because many depend on private funding for their research on influenza vaccination. CONCLUSIONS: The transparency of the NITAGs' procedures for the development of recommendations should be improved. We believe improvements might be achieved by the systematic standard evaluation of evidence, consistent voting, clear declarations of interest, and increased public funding for vaccination research. PMID- 26806678 TI - Forgone care among chronically ill patients in Germany-Results from a cross sectional survey with 15,565 individuals. AB - The decision not to seek health care although one feels that care is needed (forgone care), is influenced by various factors. Within the study "Responsiveness in ambulatory care" 15,565 chronically ill (coronary heart disease and/or type 2 diabetes) patients in Germany were surveyed in 2013. The survey included questions on forgone care, perceived discrimination when seeking care, net-income, subjective health status and subjective socioeconomic status (subSES). Survey data were linked on patient-level with administrative claims data by a German sickness fund. We applied multivariate binomial logistic regression analyses to assess the association between age, sex, comorbidities, living area, subjective health status, subSES, experienced discrimination, net equivalent income and reported forgone care. The majority in the sample are men (71.4%), the average age is 69.4 (SD: 10.2) years and 14.1% reported forgone care. In the multivariate model, we find that younger age, female gender, perceived discrimination, depression, and a poor subjective health status increase the odds of reporting forgone care. Overall, our results suggest that a negative experience with the health care system, i.e. perceived discrimination/unfair treatment, are strong predictors of forgone care among the chronically ill. PMID- 26806681 TI - Diffusion tensor imaging of the optic chiasm in patients with intra- or parasellar tumor using readout-segmented echo-planar. AB - PURPOSE: To evaluate the impact of surgery on the optic pathway of patients with intra- or parasellar mass lesions, as evidenced by readout-segmented DTI. MATERIALS AND METHODS: Twenty-four patients with intra- or parasellar mass lesions were included in the study. Readout-segmented DTI and T2WI were obtained before and after surgery. The ROIs were set on the optic chiasm as well as the anterior and posterior optic tracts. For each ROI, axial diffusivity (AD), radial diffusivity (RD), fractional anisotropy (FA), and ADC values were calculated. DTI parameters in preoperative studies of all patients were compared and related to the presence of tumor compression. In patients who underwent surgery, pre- and postoperative DTI parameters were compared. The correlation between DTI parameters and visual function was determined. RESULTS: In the preoperative studies, the optic chiasm of patients with tumor compression showed significant lower AD and RD values. The optic chiasm of patients with visual field disorder showed significantly lower AD and RD values compared to patients without the disorder. There was a negative correlation with a trend toward significance between FA values and visual field disorder scores. The comparative analysis of patients in pre- and postoperative studies showed that the optic chiasm of patients with tumor compression presented a significant lower FA (0.41 versus 0.30, p=0.0068) and higher RD values after surgery. CONCLUSIONS: DTI is a useful tool to assess the impact of surgery on the optic chiasm and nerve. PMID- 26806683 TI - Atmospheric controls on the precipitation isotopes over the Andaman Islands, Bay of Bengal. AB - Isotopic analysis of precipitation over the Andaman Island, Bay of Bengal was carried out for the year 2012 and 2013 in order to study the atmospheric controls on rainwater isotopic variations. The oxygen and hydrogen isotopic compositions are typical of the tropical marine sites but show significant variations depending on the ocean-atmosphere conditions; maximum depletion was observed during the tropical cyclones. The isotopic composition of rainwater seems to be controlled by the dynamical nature of the moisture rather than the individual rain events. Precipitation isotopes undergo systematic depletions in response to the organized convection occurring over a large area and are modulated by the integrated effect of convective activities. Precipitation isotopes appear to be linked with the monsoon intraseasonal variability in addition to synoptic scale fluctuations. During the early to mid monsoon the amount effect arose primarily due to rain re-evaporation but in the later phase it was driven by moisture convergence rather than evaporation. Amount effect had distinct characteristics in these two years, which appeared to be modulated by the intraseasonal variability of monsoon. It is shown that the variable nature of amount effect limits our ability to reconstruct the past-monsoon rainfall variability on annual to sub-annual time scale. PMID- 26806684 TI - Appraisals of psychotic experiences: an experimental investigation of symptomatic, remitted and non-need-for-care individuals. AB - BACKGROUND: Appraisals are suggested to play a determining role in the clinical outcome of psychotic experiences (PEs). We used experimental tasks that mimic PEs to investigate appraisals in individuals with PEs with and without a 'need-for clinical-care', and psychosis patients whose symptoms have remitted. We predicted that patients would appraise the tasks as threatening regardless of current symptom level, while non-clinical and control groups would appraise them as non threatening. METHOD: Appraisals following three anomalous experiences-inducing tasks [Telepath, Cards task, Virtual acoustic space paradigm (VASP)] were examined in 71 individuals: symptomatic (n = 18) and remitted (n = 16) psychosis patients; non-clinical group with PEs (n = 16); controls without PEs (n = 21). RESULTS: As predicted, symptomatic patients endorsed more threatening appraisals for all tasks than non-clinical and control groups, who did not differ from each other. However, remitted patients were less likely to endorse threatening appraisals of the Cards and Telepath than their symptomatic counterparts, although they did not differ in global ratings of how striking, threatening and distressing they found the tasks. Moreover, remitted participants endorsed more threatening appraisals of the Telepath and VASP than non-clinical participants, and of the VASP than controls. Remitted participants also rated all three tasks as globally more threatening than the non-clinical group and controls. CONCLUSIONS: Clinical outcome may not necessarily be driven by the presence of symptoms, with threatening appraisals of PEs representing a key factor. The remitted group's intermediate appraisal scores imply that the relationship between appraisal and clinical outcome is not straightforward, and potential mediating factors need to be determined. PMID- 26806685 TI - Diminished ovarian reserve: is it a neglected cause in the assessment of recurrent miscarriage? A cohort study. AB - OBJECTIVE: To study whether diminished ovarian reserve is associated with recurrent miscarriage. DESIGN: Cross-sectional clinical study. SETTING: Tertiary care center. PATIENT(S): Women with history of recurrent miscarriage (RM; n = 71) and sequentially selected age-matched fertile women who were seeking contraception (control; n = 70). INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURES(S): Serum levels of FSH, LH, E2, and antimullerian hormone (AMH); FSH/LH ratio; ovarian volumes; and antral follicle count (AFC). RESULT(S): The levels of FSH were 8.6 +/- 3.7 U/L in the RM group and 7.1 +/- 3.9 U/L in the control group; this difference was statistically significant. The levels of AMH were significantly lower in the RM group than in the control group (2.9 +/- 1.7 ng/mL vs. 3.6 +/- 1.7 ng/mL). The percentage of women with levels of FSH >=11 U/L was significantly higher in the RM group than in the control group (18.3% vs. 4.3%). In the RM group, the percentage of women with levels of AMH <=1 ng/mL was significantly higher than in the control group (19.7% vs. 5.7%). CONCLUSION(S): Recurrent miscarriage may be associated with diminished ovarian reserve. Larger prospective randomized controlled trials are warranted to better determine the predictive potential of ovarian reserve markers in recurrent miscarriage. PMID- 26806686 TI - To delay or not to delay a frozen embryo transfer after a failed fresh embryo transfer attempt? AB - OBJECTIVE: To evaluate if increasing the interval between a failed fresh embryo transfer and a subsequent frozen embryo transfer (FET) cycle has any effect on clinical pregnancy rates (CPRs). DESIGN: Retrospective cohort study. SETTING: University-based tertiary referral center. PATIENT(S): Women who underwent at least one FET after ovarian stimulation for in vitro fertilization (IVF) and a failed fresh embryo transfer attempt from January 2010 to November 2014. We divided our sample according to the "timing" of the first FET (TF-FET), defined by the interval between oocyte retrieval and the FET cycle start date. The start of the FET was classified as either immediate (<=22 days after oocyte retrieval) or delayed (>22 days after oocyte retrieval). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): CPR after the first FET. RESULT(S): A total of 1,183 FET cycles (performed in 1,087 women) were included in our study. No significant differences were found between the immediate and delayed FET groups regarding age, number of oocytes retrieved, number of good-quality embryos produced, embryo developmental stage at FET, and number of frozen embryos transferred. Most importantly, the CPRs of the first FET did not differ significantly according to the TF-FET (32.5% after immediate FET vs. 31.7% after delayed FET), even after adjusting for potential confounding with the use of multivariable logistic regression. CONCLUSION(S): FETs performed immediately after fresh IVF cycles had CPRs similar to those postponed to a later time. Therefore, deferring FETs may unnecessarily prolong time to pregnancy. PMID- 26806687 TI - Low-density lipoprotein transport through an arterial wall under hyperthermia and hypertension conditions--An analytical solution. AB - An analytical solution for Low-Density Lipoprotein transport through an arterial wall under hyperthermia conditions is established in this work. A four-layer model is used to characterize the arterial wall. Transport governing equations are obtained as a combination between Staverman-Kedem-Katchalsky membrane equations and volume-averaged porous media equations. Temperature and solute transport fields are coupled by means of Ludwig-Soret effect. Results are in excellent agreement with numerical and analytical literature data under isothermal conditions, and with numerical literature data for the hyperthermia case. Effects of hypertension combined with hyperthermia, are also analyzed in this work. PMID- 26806688 TI - Particle deposition in a realistic geometry of the human conducting airways: Effects of inlet velocity profile, inhalation flowrate and electrostatic charge. AB - Understanding the multitude of factors that control pulmonary deposition is important in assessing the therapeutic or toxic effects of inhaled particles. The use of increasingly sophisticated in silico models has improved our overall understanding, but model realism remains elusive. In this work, we use Large Eddy Simulations (LES) to investigate the deposition of inhaled aerosol particles with diameters of dp=0.1,0.5,1,2.5,5 and 10MUm (particle density of 1200kg/m(3)). We use a reconstructed geometry of the human airways obtained via computed tomography and assess the effects of inlet flow conditions, particle size, electrostatic charge, and flowrate. While most computer simulations assume a uniform velocity at the mouth inlet, we found that using a more realistic inlet profile based on Laser Doppler Anemometry measurements resulted in enhanced deposition, mostly on the tongue. Nevertheless, flow field differences due to the inlet conditions are largely smoothed out just a short distance downstream of the mouth inlet as a result of the complex geometry. Increasing the inhalation flowrate from sedentary to activity conditions left the mean flowfield structures largely unaffected. Nevertheless, at the higher flowrates turbulent intensities persisted further downstream in the main bronchi. For dp>2.5MUm, the overall Deposition Fractions (DF) increased with flowrate due to greater inertial impaction in the oropharynx. Below dp=1.0MUm, the DF was largely independent of particle size; it also increased with flowrate, but remained significantly lower. Electrostatic charge increased the overall DF of smaller particles by as much as sevenfold, with most of the increase located in the mouth-throat. Moreover, significant enhancement in deposition was found in the left and right lung sub regions of our reconstructed geometry. Although there was a relatively small impact of inhalation flowrate on the deposition of charged particles for sizes dp<2.5MUm, impaction prevailed over electrostatic deposition for larger particles as the flowrate was increased. Overall, we report a significant interplay between particle size, electrostatic charge, and flowrate. Our results suggest that in silico models should be customized for specific applications, ensuring all relevant physical effects are accounted for in a self-consistent fashion. PMID- 26806689 TI - Soft tissues store and return mechanical energy in human running. AB - During human running, softer parts of the body may deform under load and dissipate mechanical energy. Although tissues such as the heel pad have been characterized individually, the aggregate work performed by all soft tissues during running is unknown. We therefore estimated the work performed by soft tissues (N=8 healthy adults) at running speeds ranging 2-5 m s(-1), computed as the difference between joint work performed on rigid segments, and whole-body estimates of work performed on the (non-rigid) body center of mass (COM) and peripheral to the COM. Soft tissues performed aggregate negative work, with magnitude increasing linearly with speed. The amount was about -19 J per stance phase at a nominal 3 m s(-1), accounting for more than 25% of stance phase negative work performed by the entire body. Fluctuations in soft tissue mechanical power over time resembled a damped oscillation starting at ground contact, with peak negative power comparable to that for the knee joint (about 500 W). Even the positive work from soft tissue rebound was significant, about 13 J per stance phase (about 17% of the positive work of the entire body). Assuming that the net dissipative work is offset by an equal amount of active, positive muscle work performed at 25% efficiency, soft tissue dissipation could account for about 29% of the net metabolic expenditure for running at 5 m s(-1). During running, soft tissue deformations dissipate mechanical energy that must be offset by active muscle work at non-negligible metabolic cost. PMID- 26806690 TI - Rotational kinematics of pelvis and upper trunk at butterfly stroke: Can fins affect the dynamics of the system? AB - The purpose of the present study was to investigate the rotational kinematics pattern of the upper trunk and the pelvis and the complexity-variability of their movement, during the sprint butterfly stroke between male and female swimmers with long fins (18-26 cm) and without fins. Two pairs of 3D accelerometers and gyroscopes were used to measure segments' flexion-extension angles. There were no gender differences apart from the record. The amplitude values at the pelvis were significantly larger when swimming without fins while at the C7 they were significantly larger when swimming with them. Autocorrelation coefficients of angles' time histories were higher when swimming with fins for both segments. The power spectrums revealed a dominant frequency representing the stroke period which grew significantly stronger for the fin condition. Correlation Dimension verified a lower dimensionality for the fin condition for the C7 segment movement pattern. Overall fin use seems to offer "strength" to the swimmer's movement pattern. This does not imply better movement coordination, but rather a trend toward a more stable attractor. PMID- 26806691 TI - Layer-by-Layer Assembly of Metal-Organic Frameworks in Macroporous Polymer Monolith and Their Use for Enzyme Immobilization. AB - New monolithic materials comprising zeolitic imidazolate framework (ZIF-8) located on the pore surface of poly(glycidyl methacrylate-co-ethylene dimethacrylate) monolith previously functionalized with N-(3-aminopropyl) imidazole have been prepared via a layer-by-layer self-assembly strategy. These new ZIF-8@monolith hybrids are used as solid-phase carriers for enzyme immobilization. Their performance is demonstrated with immobilization of a model proteolytic enzyme trypsin. The best of the conjugates enable very efficient digestion of proteins that can be achieved in mere 43 s. PMID- 26806692 TI - Technically Successful Geniculate Artery Embolization Does Not Equate Clinical Success for Treatment of Recurrent Knee Hemarthrosis after Knee Surgery. AB - PURPOSE: To evaluate technical details, clinical outcomes, and complications in patients undergoing geniculate artery embolization for treatment of spontaneous hemarthrosis after knee surgery. MATERIALS AND METHODS: During 2009-2014, 10 consecutive patients (seven women; mean age, 57.4 y) underwent geniculate artery embolization at a single tertiary care center. All patients except one had hemarthrosis after total knee replacement (TKR). One patient presented with hemarthrosis after cartilage surgery. Two patients in the TKR group had a history of TKR revisions before the embolization. Embolization was performed with polyvinyl alcohol particles (range, 300-700 um). In one patient requiring repeat embolization, N-butyl cyanoacrylate/ethiodized oil was used. The endpoint for embolization was stasis in the target artery and elimination of the hyperemic blush. RESULTS: In 10 patients, 14 embolizations were performed with 100% technical success. Hemarthrosis resolved in six patients. Four patients required repeat embolization for recurrent hemarthrosis, which subsequently resolved in two of four patients. Three of the four patients who required repeat embolization had serious comorbidities, either blood dyscrasias or therapeutic anticoagulation. There were two minor skin complications that resolved with conservative management. The average length of follow-up after embolization was 545 days (range, 50-1,655 d). One patient was lost to follow-up. CONCLUSIONS: Geniculate artery embolization is a safe, minimally invasive treatment option for spontaneous and refractory knee hemarthrosis after knee surgery with 100% technical success. However, limited clinical success and higher repeat embolization rates were noted in patients with serious comorbidities. PMID- 26806693 TI - Uterine Artery Embolization before Delivery to Prevent Postpartum Hemorrhage. AB - PURPOSE: To assess the safety and outcomes of uterine artery embolization (UAE) performed before delivery in patients with placental implant anomalies at high risk for peripartum or postpartum hemorrhage. MATERIALS AND METHODS: From January 2013 to January 2015, 50 consecutive patients with placental implant anomalies at 35-36 weeks of pregnancy were recruited. UAE was performed superselectively by injecting reabsorbable pledgets. We applied 5 dosimeters to patients' backs to measure the uterine radiation dose, considered to be the same radiation dose that the fetus received. Newborns were assessed immediately after birth and at 6-month follow-up. RESULTS: All procedures were technically successful. Of patients, 64% did not require transfusions. Mean blood units transfused was 0.7 U (range, 0-4 U). No patient was transferred to the intensive care unit. Hysterectomy was performed in 13 patients (26%). Mean fluoroscopy operative time was 3 minutes 42 seconds (range, 1 min 21 s-6 min 58 s), and mean uterine radiation dose was 15.61 mGy (range, 8.15-38.18 mGy). Mean time between embolization and delivery was 6 minutes 4 seconds (range, 4 min 18 s-8 min 12 s). The 1-minute and 5-minute Apgar scores were 8-9 in all newborns; 8 newborns were lost to follow-up at 6 months. A normal cognitive outcome was evident in all 42 children studied. CONCLUSIONS: UAE before delivery appeared to reduce bleeding during cesarean sections in this consecutive series of patients with placental implant anomalies. In the hands of experienced staff, radiation dose to the fetus was minimal. PMID- 26806694 TI - Better Outcomes if Percutaneous Drainage Is Used Early and Proactively in the Course of Necrotizing Pancreatitis. AB - PURPOSE: To compare outcomes after percutaneous catheter drainage (PCD) for acute necrotizing pancreatitis versus those in a randomized controlled trial as a reference standard. MATERIALS AND METHODS: Between September 2010 and August 2014, CT-guided PCD was the primary treatment for 39 consecutive patients with pancreatic necrosis. The indication for PCD was the clinical finding of uncontrolled pancreatic juice leakage rather than infected necrosis. Subsequent to PCD, the drains were proactively studied with fluoroscopic contrast medium every 3 days to ensure patency and position. Drains were ultimately maneuvered to the site of leakage. These 39 patients were compared with 43 patients from the Pancreatitis, Necrosectomy versus Step-up Approach (PANTER) trial. RESULTS: The CT severity index was similar between studies (median of 8 in each). Time from onset of acute pancreatitis to PCD was shorter in the present series (median, 23 d vs 30 d). The total number of procedures (PCD and subsequent fluoroscopic drain studies) per patient was greater in the present series (mean, 14 vs 2). More patients in the PANTER trial had organ failure (62% vs 84%), required open or endoscopic necrosectomy (0% vs 60%), and experienced in-hospital mortality (0% vs 19%; P < .05 for all). CONCLUSIONS: Even though patients in the present series had a similar CT severity index as those in the PANTER trial, the former group showed lower incidences of organ failure, need for necrosectomy, and in-hospital mortality. The use of a proactive PCD protocol early, before the development of severe sepsis, appeared to be effective. PMID- 26806695 TI - Influence of type and proportion of lyoprotectants on lyophilized ginsenoside Rg3 liposomes. AB - OBJECTIVES: To improve stability and shelf life, lyophilized formulations of 20(R)-Ginsenoside Rg3 liposomes (G-Rg3-Ls) were prepared. METHODS: Glucose, trehalose, sucrose, maltose, lactose, mannitol, inositol, hydroxypropyl-beta cyclodextrin and polyethylene glycol were used as single lyoprotectant and then compared in terms of their ability to protect lyophilized G-Rg3-Ls. Further, a glucose-mannitol complex was used to determine the optimal lyophilized preparation. The analysis of lyophilized liposomes or lyoprotectant was further investigated by scanning electron microscopy, thermogravimetry-differential thermal analysis, X-ray diffractometry and Fourier transform infrared spectroscopy. Cytotoxicity assay was used to assess the cyto-inhibition of freshly prepared and lyophilized liposomes. KEY FINDINGS: When the ratio of glucose-mannitol to phospholipids was 4 : 2 : 1 (w/w) the lyophilized G-Rg3-Ls exhibited good appearance, high DRR (86.52% +/- 5.02%), small change in particle size (45.83 +/- 0.50%) and short rehydration reconstruction time (8.3 +/- 1.5 s). All indices were considerably better than those of each single protective agent. Results indicated that when the two lyoprotectants were combined, the stabilizing effect of glucose and shaping effect of mannitol were well maintained. The cyto inhibition of freshly prepared and lyophilized G-Rg3 liposomes showed that lyophilization did not affect the bioactivity of G-Rg3. CONCLUSIONS: The application of glucose-mannitol composite lyoprotectants can obtain a good G-Rg3 lyophilized preparation. PMID- 26806696 TI - Biodistribution, hypouricemic efficacy and therapeutic mechanism of morin phospholipid complex loaded self-nanoemulsifying drug delivery systems in an experimental hyperuricemic model in rats. AB - OBJECTIVES: This study aimed to compare the biodistribution and hypouricemic efficacy of morin and morin-phospholipid complex loaded self-nanoemulsifying drug delivery systems (MPC-SNEDDS), as well as to explore their therapeutic mechanisms. METHODS: We studied the biodistribution of morin and MPC-SNEDDS after they were orally administered to rats. The hypouricemic efficacy and the therapeutic mechanisms of morin and MPC-SNEDDS were evaluated using potassium oxonate-induced hyperuricemic model in rats. KEY FINDINGS: With enhanced morin concentration in liver and kidney, oral delivery of MPC-SNEDDS exhibited significantly stronger urate-lowering effect in hyperuricemic rats than morin. The hypouricemic efficacy of morin was due to reduced production of uric acid via inhibiting the mRNA expression of hepatic xanthine dehydrogenase/xanthine oxidase (XDH/XO), as well as decreased urate reabsorption via modulating the alteration of mRNA levels of glucose transporter (mGLUT9), renal organic anion transporter 1 (mOAT1) and uric acid transporter (mURAT1). MPC-SNEDDS dually inhibited mRNA expression and activity of hepatic XDH/XO and restored the dysregulation of renal mGLUT9, mOAT1 and mURAT1, contributing to its superior urate-lowering efficacy. CONCLUSION: The results demonstrated the great potential of MPC-SNEDDS as an alternative oral strategy for active agents in treating hyperuricemia. PMID- 26806697 TI - The C-terminal tails of 4,4'-diphenylmethane-bis(methyl) carbamate are essential for binding to receptor for advanced glycation end products to attenuate advanced glycation end products-induced inflammation and apoptosis responses in human umbilical vein endothelial cells. AB - OBJECTIVES: A novel compound 4,4'-diphenylmethane-bis(methyl) carbamate (CM1) was shown to possess preventive activity on AGEs-induced human umbilical vein endothelial cells (HUVECs) damage via binding to RAGE. However, the underlying structural basis of CM1 on binding to RAGE was not fully understood. METHODS: In the present study, CM1 analogues were designed and synthesized to compare the activity differences on inhibiting AGEs-induced inflammatory response including TGF-beta1, RAGE protein expression in HUVECs, and macrophages migration and adhesion to HUVECs. In addition, the cell viability and anti-apoptosis activities of CM1 analogues were also examined. KEY FINDINGS: These results indicated that CM1 had higher activities on preventing AGEs-induced HUVECs damage (inflammation, cell viability and apoptosis) than other analogues. The bioaffinity assay was conducted by CMC and demonstrated that the IC50 and dissociation equilibrium constants (Kd) of CM1 were lower whereas the Bmax was higher than other analogues. The incubation of RAGE protein with CM1 analogues by equilibrium dialysis method showed CM1 had a stronger binding rate than other CM1 analogues. CONCLUSION: Our findings suggested that the C-terminal tails (methoxycarbonyl groups) of CM1 were the active groups for binding to RAGE and then led to the attenuation on RAGE-mediated endothelial dysfunction. PMID- 26806698 TI - Wild ginseng cambial meristematic cells ameliorate hepatic steatosis and mitochondrial dysfunction in high-fat diet-fed mice. AB - OBJECTIVES: The aim of this study was to determine the protective mechanisms of wild ginseng cambial meristematic cells (CMCs) on non-alcoholic fatty liver disease in high-fat diet (HFD)-fed mice. METHODS: Male C57BL/6 mice received either normal-fat diet or HFD for 10 weeks along with wild ginseng CMCs (75, 150 and 300 mg/kg) or vehicle (0.5% carboxyl methyl cellulose) by oral administration once a day. Triglyceride and total cholesterol contents were measured in liver and serum samples. Parameters for hepatic lipid metabolism and mitochondria biogenesis were assessed. KEY FINDINGS: Treatment with wild ginseng CMCs markedly attenuated body weight, serum and hepatic lipid contents, and serum aminotransferase activity. While wild ginseng CMCs attenuated the increases in sterol regulatory element-binding transcription factor 1 (SREBP-1) and carbohydrate-responsive element-binding protein (ChREBP) expression, it enhanced the increases in carnitine palmitoyltransferase 1A (CPT1A) and peroxisome proliferator-activated receptor alpha (PPAR-alpha) expression. HFD decreased glutamate dehydrogenase activity and glutathione content, and increased lipid peroxidation, which were all attenuated by wild ginseng CMCs. Furthermore, wild ginseng CMCs enhanced mitochondrial biogenesis-related factors, including peroxisome proliferator-activated receptor-gamma co activator 1alpha (PGC1alpha), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM). CONCLUSIONS: Wild ginseng CMCs protect against HFD-induced liver injury, which prevents lipid accumulation and mitochondrial oxidative stress, and enhances mitochondrial biogenesis. PMID- 26806702 TI - A quantitative validated model reveals two phases of transcriptional regulation for the gap gene giant in Drosophila. AB - Understanding eukaryotic transcriptional regulation and its role in development and pattern formation is one of the big challenges in biology today. Most attempts at tackling this problem either focus on the molecular details of transcription factor binding, or aim at genome-wide prediction of expression patterns from sequence through bioinformatics and mathematical modelling. Here we bridge the gap between these two complementary approaches by providing an integrative model of cis-regulatory elements governing the expression of the gap gene giant (gt) in the blastoderm embryo of Drosophila melanogaster. We use a reverse-engineering method, where mathematical models are fit to quantitative spatio-temporal reporter gene expression data to infer the regulatory mechanisms underlying gt expression in its anterior and posterior domains. These models are validated through prediction of gene expression in mutant backgrounds. A detailed analysis of our data and models reveals that gt is regulated by domain-specific CREs at early stages, while a late element drives expression in both the anterior and the posterior domains. Initial gt expression depends exclusively on inputs from maternal factors. Later, gap gene cross-repression and gt auto-activation become increasingly important. We show that auto-regulation creates a positive feedback, which mediates the transition from early to late stages of regulation. We confirm the existence and role of gt auto-activation through targeted mutagenesis of Gt transcription factor binding sites. In summary, our analysis provides a comprehensive picture of spatio-temporal gene regulation by different interacting enhancer elements for an important developmental regulator. PMID- 26806701 TI - The SWI/SNF BAF-A complex is essential for neural crest development. AB - Growing evidence indicates that chromatin remodeler mutations underlie the pathogenesis of human neurocristopathies or disorders that affect neural crest cells (NCCs). However, causal relationships among chromatin remodeler subunit mutations and NCC defects remain poorly understood. Here we show that homozygous loss of ARID1A-containing, SWI/SNF chromatin remodeling complexes (BAF-A) in NCCs results in embryonic lethality in mice, with mutant embryos succumbing to heart defects. Strikingly, monoallelic loss of ARID1A in NCCs led to craniofacial defects in adult mice, including shortened snouts and low set ears, and these defects were more pronounced following homozygous loss of ARID1A, with the ventral cranial bones being greatly reduced in size. Early NCC specification and expression of the BRG1 NCC target gene, PLEXINA2, occurred normally in the absence of ARID1A. Nonetheless, mutant embryos displayed incomplete conotruncal septation of the cardiac outflow tract and defects in the posterior pharyngeal arteries, culminating in persistent truncus arteriosus and agenesis of the ductus arteriosus. Consistent with this, migrating cardiac NCCs underwent apoptosis within the circumpharyngeal ridge. Our data support the notion that multiple, distinct chromatin remodeling complexes govern genetically separable events in NCC development and highlight a potential pathogenic role for NCCs in the human BAF complex disorder, Coffin-Siris Syndrome. PMID- 26806700 TI - Stroke injury, cognitive impairment and vascular dementia. AB - The global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25-30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood-brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID- 26806703 TI - Early preimplantation cells expressing Cdx2 exhibit plasticity of specification to TE and ICM lineages through positional changes. AB - The establishment of the trophectoderm (TE) and the inner cell mass (ICM) is the first cell lineage segregation to occur in mouse preimplantation development. These two cell lineages arise in a position-dependent manner at the blastocyst stage: the outer cells form TE, which will generate the future placenta, while the inner cells give rise to the ICM, from which the epiblast (EPI) and primitive endoderm (PrE) arise. Previous studies have shown that a portion of cells relocate from the outside position to the inside during this preimplantation stage, but few studies have investigated the correlation between cell relocation and the expression of key transcription factors critical for cell differentiation. To monitor cell movement and the status of the TE-specification pathway in living embryos, we established Cdx2-GFP reporter mice allowing us to visualize the expression of Caudal-type transcriptional factor (Cdx2), a key regulator of the initiation of TE differentiation. Observation of Cdx2-GFP preimplantation embryos by live cell imaging revealed that all cells localized in an initial outer position initiated the expression of Cdx2. Subsequently, cells that changed their position from an outer to an inner position downregulated Cdx2 expression and contributed to the ICM. Finally we showed that internalized cells likely contribute to both the EPI and PrE. Our datas indicate that cells expressing even high levels of Cdx2 can internalize, deactivate an activated TE specification molecular pathway and integrate into the pluripotent cell population. PMID- 26806704 TI - Hmga2 is required for neural crest cell specification in Xenopus laevis. AB - HMGA proteins are small nuclear proteins that bind DNA by conserved AT-hook motifs, modify chromatin architecture and assist in gene expression. Two HMGAs (HMGA1 and HMGA2), encoded by distinct genes, exist in mammals and are highly expressed during embryogenesis or reactivated in tumour progression. We here addressed the in vivo role of Xenopus hmga2 in the neural crest cells (NCCs). We show that hmga2 is required for normal NCC specification and development. hmga2 knockdown leads to severe disruption of major skeletal derivatives of anterior NCCs. We show that, within the NCC genetic network, hmga2 acts downstream of msx1, and is required for msx1, pax3 and snail2 activities, thus participating at different levels of the network. Because of hmga2 early effects in NCC specification, the subsequent epithelial-mesenchymal transition (EMT) and migration of NCCs towards the branchial pouches are also compromised. Strictly paralleling results on embryos, interfering with Hmga2 in a breast cancer cell model for EMT leads to molecular effects largely consistent with those observed on NCCs. These data indicate that Hmga2 is recruited in key molecular events that are shared by both NCCs and tumour cells. PMID- 26806705 TI - PLD1 regulates Xenopus convergent extension movements by mediating Frizzled7 endocytosis for Wnt/PCP signal activation. AB - Phospholipase D (PLD) is involved in the regulation of receptor-associated signaling, cell movement, cell adhesion and endocytosis. However, its physiological role in vertebrate development remains poorly understood. In this study, we show that PLD1 is required for the convergent extension (CE) movements during Xenopus gastrulation by activating Wnt/PCP signaling. Xenopus PLD1 protein is specifically enriched in the dorsal region of Xenopus gastrula embryo and loss or gain-of-function of PLD1 induce defects in gastrulation and CE movements. These defective phenotypes are due to impaired regulation of Wnt/PCP signaling pathway. Biochemical and imaging analysis using Xenopus tissues reveal that PLD1 is required for Fz7 receptor endocytosis upon Wnt11 stimulation. Moreover, we show that Fz7 endocytosis depends on dynamin and regulation of GAP activity of dynamin by PLD1 via its PX domain is crucial for this process. Taken together, our results suggest that PLD1 acts as a new positive mediator of Wnt/PCP signaling by promoting Wnt11-induced Fz7 endocytosis for precise regulation of Xenopus CE movements. PMID- 26806706 TI - Health information exchanges--Unfulfilled promise as a data source for clinical research. AB - OBJECTIVE: To determine the use of health information exchange organizations (HIEs) to support and conduct clinical research. MATERIALS AND METHODS: This scoping review included US-based studies published between January 2003 and March 2014 that used data from an HIE to address at least one of three categories of research: clinical or epidemiological research, financial evaluation, or utilization of health services. Eligibility was not restricted to research on HIEs. Studies with research questions outside of the evaluation of HIEs themselves were sought. RESULTS: Eighteen articles met final study inclusion criteria from an initial list of 847 hits. Fifteen studies addressed a clinical or epidemiological research question, 6 addressed a financial consideration, and 8 addressed a utilization issue. Considerable overlap was found among the research categories: 13 articles addressed more than one category. Of the eighteen included studies, only two used HIE data to answer a research objective that was NOT specific to HIE use. Research designs were varied and ranged from observational studies, such as cohort and cross-sectional studies, to randomized trials. The 18 articles represent the involvement of a small number of HIEs; 7 of the studies were from a single HIE. DISCUSSION: This review demonstrates that HIE provided information is available and used to answer clinical or epidemiological, financial, or utilization-based research questions; however, the majority of the studies using HIE data are done with the primary goal of evaluating the use and impact of HIEs on health care delivery and outcomes. As HIEs mature and become integrated parts of the health care industry, the authors anticipate that fewer studies will be published that describe or validate the role of HIEs, and more will use HIEs as multi-institutional data sources for conducting clinical research and improving health services and clinical outcomes. CONCLUSION: Articles identified in this review indicate the limited extent that HIE data are being used for clinical research outside of the evaluation of HIEs themselves, as well as the limited number of specific HIEs that are involved in generating published research. Significant barriers exist that prevent HIEs from developing into an invaluable resource for clinical research including technological infrastructure limitations, business processes limiting secondary use of data, and lack of participating provider support. Research to better understand challenges to developing the necessary infrastructure and policies to foster HIE engagement in research would be valuable as HIEs represent an opportunity to engage non-traditional health care provider research partners. PMID- 26806707 TI - Barriers to patient participation in a self-management and education website Renal PatientView: A questionnaire-based study of inactive users. AB - OBJECTIVES: The Renal PatientView (RPV) website is an information and education tool aimed at increasing patient involvement in their care. We have conducted this study to elucidate why some users remain inactive on RPV despite initially signing up for the service. METHODS: Patients at a teaching hospital in United Kingdom, who originally signed up for RPV but are no longer active (no logins during previous 6 months), were sent paper questionnaires. Responses were collected for up to 6 months. RESULTS: Of the 190 questionnaires, 69 (39%) were returned partially or fully completed. Majority of respondents could access computer (94%) and internet (91%) from home. Reasons for inactivity among survey respondents included: loss of login credentials (45%), perception that it did not add anything to existing care (37%), being too busy (13%) and anxiety of viewing results from home (10%). Thirty-seven respondents provided free-text comments. Thematic analysis of these reinforced above findings and also indicated that despite infrequent use, some patients valued RPV availability. Patients made very little reference to using sections of the website other than test results. CONCLUSIONS: Patients find RPV a valuable resource. It is, however, mainly seen as a portal to check blood test results; other sections of the website aimed at promoting self-management remain underutilized. Several local and central level changes, such as a robust system of user accounts handling, improved promotion, and emphasis on further development of self-management sections of RPV may help improve participation. PMID- 26806708 TI - Optimizing the user interface of a data entry module for an electronic patient record for cardiac rehabilitation: A mixed method usability approach. AB - INTRODUCTION: Cumbersome electronic patient record (EPR) interfaces may complicate data-entry in clinical practice. Completeness of data entered in the EPR determines, among other things, the value of computerized clinical decision support (CCDS). Quantitative usability evaluations can provide insight into mismatches between the system design model of data entry and users' data entry behavior, but not into the underlying causes for these mismatches. Mixed method usability evaluation studies may provide these insights, and thus support generating redesign recommendations for improving an EPR system's data entry interface. AIM: To improve the usability of the data entry interface of an EPR system with CCDS in the field of cardiac rehabilitation (CR), and additionally, to assess the value of a mixed method usability approach in this context. METHODS: Seven CR professionals performed a think-aloud usability evaluation both before (beta-version) and after the redesign of the system. Observed usability problems from both evaluations were analyzed and categorized using Zhang et al.'s heuristic principles of good interface design. We combined the think-aloud usability evaluation of the system's beta-version with the measurement of a new usability construct: users' deviations in action sequence from the system's predefined data entry order sequence. Recommendations for redesign were implemented. We assessed whether the redesign improved CR professionals' (1) task efficacy (with respect to the completeness of data they collected), and (2) task efficiency (with respect to the average number of mouse clicks they needed to complete data entry subtasks). RESULTS: With the system's beta version, 40% of health care professionals' navigation actions through the system deviated from the predefined next system action. The causes for these deviations as revealed by the think-aloud method mostly concerned mismatches between the system design model for data entry action sequences and users expectations of these action sequences, based on their paper-based daily routines. This caused non completion of data entry tasks (31% of main tasks completed), and more navigation actions than minimally required (146% of the minimum required). In the redesigned system the data entry navigational structure was organized in a flexible way around an overview screen to better mimic users' paper-based daily routines of collecting patient data. This redesign resulted in an increased number of completed main tasks (70%) and a decrease in navigation actions (133% of the minimum required). The think-aloud usability evaluation of the redesigned system showed that remaining problems concerned flexibility (e.g., lack of customization options) and consistency (mainly with layout and position of items on the screen). CONCLUSION: The mixed method usability evaluation was supportive in revealing the magnitude and causes of mismatches between the system design model of data-entry with users' data entry behavior. However, as both task efficacy and efficiency were still not optimal with the redesigned EPR, we advise to perform a cognitive analysis on end users' mental processes and behavior patterns in daily work processes specifically during the requirements analysis phase of development of interactive healthcare information systems. PMID- 26806709 TI - The moderating effects of demographic and individual characteristics on nurses' acceptance of information systems: A canadian study. AB - OBJECTIVES: The purpose of this study was to educate on the moderating effects of demographic (i.e., educational level and age) and individual characteristics (i.e., years of nursing experience and computer knowledge) on nurses' acceptance of information systems (IS). The technology acceptance model (TAM) with its constituent variables such as perceived usefulness (PUSS) and perceived ease of use (PEOU) was the theoretical framework used for this study. METHODS: A cross sectional study was conducted in Nova Scotia, Canada. Usable data was collected from 197 registered nurses (RNs). Relevant hypotheses were formulated and the partial least squares (PLS) technique was used for data analysis. RESULTS: The results of the hypothesized relationships showed that education and computer knowledge have positive moderating effects on the influences of PEOU and PUSS on nurses' attitudes toward IS (ATTI). The factors of nurses' years of nursing experience and age did not yield meaningful results. ATTI impacted behavioral intentions to use IS, which positively impacted nurses' use of IS. The nurses sampled in the study have positive IS use behaviors. CONCLUSIONS: This study demonstrates that relevant demographic factors and individual characteristics, if incorporated into frameworks used for investigating nurses' acceptance of IS, could permit the emergence of useful insights for practitioners and researchers. Specifically, this study showed that nurses with higher educational attainments and more basic computer knowledge readily accept implemented IS at work. Hospital administrators benefit from insights such as the one presented in this study. PMID- 26806710 TI - The effect of registry-based performance feedback via short text messages and traditional postal letters on prescribing parenteral steroids by general practitioners--A randomized controlled trial. AB - BACKGROUND: It is conjectured that providing feedback on physicians' prescribing behavior improves quality of drug prescriptions. However, the effectiveness of feedback provision and mode of feedback delivery is not well understood. The objective of this study was to assess and compare the effect of traditional paper letters (TPL) and short text message (STM) feedback on general practitioners' prescribing behavior of parenteral steroids (PSs). METHODS: In a single-blind randomized controlled trial, 906 general practitioners (GPs) having at least 10 monthly prescriptions were randomly recruited into two interventions and one control study arms with 1:1 allocation, stratified by percentage of prescriptions. The intervention was the provision of 3 feedback messages containing prescribing indices in TPL and STM (in the first two arms) versus the control arm (CG) with an interval of 3 months between these messages. We calculated the PS Defined Daily Dose (DDD) for every GP, every month, and compared between the 3 arms, before and after the interventions. The expected primary outcome was to reduce prescription of parenteral steroids by participants. The study was performed in the Kerman Social Security Organization in Iran. RESULTS: A total of 906 GPs were selected for the trial, but only 721 of them (TPL=191, STM=228, CG=302) were recruited for the 1st feedback. The mean age of GPs was 44 and 59% of them were male. The prescribed parenteral steroid DDDs at baseline were similar (TPL=121.62, STM=127.49, CG=115.68, P>0.5). At the end of the study, DDDs in the TPL and STM arms were similar (TPL=104.38, STM=101.90, P>0.9) but DDDs in each intervention arm was statistically significantly lower than in CG (CG=156.17, P<0.0001). Being in TPL and STM arms resulted in 36.1 and 41.7 units of decrease in DDD respectively, compared to the control arm (P<0.02 and P<0.005) after the one-year duration of the study. CONCLUSION: Feedback by TPLs and STMs on prescribing performance effectively reduced prescribing PSs by GPs. STM, being a cheap and fast tool, is potentially powerful and efficient for drug prescription rationalization. PMID- 26806711 TI - Factors affecting physicians' use of a dedicated overview interface in an electronic health record: The importance of standard information and standard documentation. AB - BACKGROUND: It remains a continual challenge to present information in user interfaces in large IT systems to support overview in the best possible way. We here examine how an electronic health record (EHR) supports the creation of overview among hospital physicians with a particular focus on the use of an interface designed to provide clinicians with a patient information overview. The overview interface integrates information flexibly from diverse places in the EHR and presents this information in one screen display. Our study revealed widespread non-use of the overview interface. We explore the reasons for its use and non-use. METHOD: We conducted exploratory ethnographic fieldwork among physicians in two hospitals and gathered statistical data on their use of the overview interface. From the quantitative data, we identified where the interface was used most and conducted 18 semi-structured, open-ended interviews framed by the theoretical framework and the findings of the initial ethnographic fieldwork. We interviewed both physicians and employees from the IT units in different hospitals. We then analysed notes from the ethnographic fieldwork and the interviews and ordered these into themes forming the basis for the presentation of findings. RESULTS: The overview interface was most used in departments or situations where the problem at hand and the need for information could be standardized-in particular, in anesthesiological departments and outpatient clinics. However, departments with complex and long patient histories did not make much use of the overview interface. Design and layout were not mentioned as decisive factors affecting its use or non-use. Many physicians questioned the completeness of data in the overview interface-either because they were skeptical about the hospital's or the department's documentation practices, or because they could not recognize the structure of the interface. This uncertainty discouraged physicians from using the overview interface. CONCLUSION: Dedicating a specific function or interface to supporting overview works best where information needs can be standardized. The narrative and contextual nature of creating clinical overview is unlikely to be optimally supported by using the overview interface alone. The use of these kinds of interfaces requires trust in data completeness and other clinicians' and administrative staff's documentation practices, as well as an understanding of the underlying structure of the EHR and how information is filtered when data are aggregated for the interface. PMID- 26806713 TI - Health information exchange and information gaps in referrals to a pediatric emergency department. AB - OBJECTIVE: to assess the extent of information gaps between three information sources available at admission to a pediatric Emergency Department (ED): Health Information Exchange (HIE) system, physicians' referral letters and information collected from patients/parents at admission to the ED (patient's medical history). MATERIALS AND METHODS: A retrospective cohort study of 170 medical records of children aged 6 months to 18 years referred to a pediatric ED for a common childhood disease. Each record was reviewed for information on lab and imaging tests, vaccinations, allergies, previous diagnoses, recent and chronic medical treatment in the HIE system and referral letter, or from the patient's medical history taken on admission to the ED. The percent overlap between information sources and information gaps was assessed. RESULTS: The most informative source, in terms of addressing all key areas, was the patient's medical history, with an average of 73.5% indication of each information key area. Next was the HIE system, with 54.1% indication of each key area; the least informative was the referral letter (43.9%). The overall overlap in data availability among all information sources occurred on average in 23% of the cases. HIE's ability to provide data missing from other routinely available sources was mainly in the area of chronic medication dosages (37% of cases). CONCLUSIONS: Each of the three major information sources available at admission to a pediatric ED lack important data and each makes its own unique contribution. Improving documentation in electronic health records, on which HIE systems feed from can narrow significant information gaps at the most critical time-point admission to a pediatric ED. PMID- 26806712 TI - Effects of eHealth for patients and informal caregivers confronted with cancer: A meta-review. AB - BACKGROUND: eHealth can be defined as information provision about illness or health care and/or support for patients and/or informal caregivers, using the computer or related technologies. eHealth interventions are increasingly being used in cancer care, e.g. to support patients and informal caregivers in managing symptoms and problems in daily life. OBJECTIVES: To synthesize evidence from systematic reviews on the effects of eHealth for cancer patients or their informal caregivers. MATERIALS AND METHODS: A systematic meta-review, in the sense of a systematic review of reviews, was conducted. Searches were performed in PubMed, Embase, CINAHL, PsycINFO, and the Cochrane Library. All steps in the review process were either performed by two reviewers independently or checked by a second reviewer. Disagreements were resolved by consensus. RESULTS: Ten systematic reviews were included. All reviews focused on the effects of eHealth for patients and none on effects for informal caregivers. Except for one review of high methodological quality, all reviews were of moderate methodological quality. Evidence was found for effects on perceived support, knowledge levels, and information competence of cancer patients. Indications of evidence were found for health status and healthcare participation. Findings were inconsistent for outcomes related to decision-making, psychological wellbeing, depression and anxiety, and quality of life. No evidence was found for effects on physical and functional wellbeing. CONCLUSION: There is evidence for positive effects of eHealth on perceived support, knowledge, and information competence of cancer patients. For effects on other outcomes in cancer patients, findings are mainly inconsistent or lacking. This meta-review did not find relevant reviews focusing on or including the effects of eHealth on informal caregivers, which seems a rather unexplored area. PMID- 26806714 TI - The impact of post-adoption beliefs on the continued use of health apps. AB - BACKGROUND: Recently, there has been a rapid increase in the development and use of health apps on smartphones. In spite of research on such technologies, there exist considerable gaps between health app use and our understandings of such technology. Therefore, this study explored the process of leading people to keep using health apps, mainly based on the post-acceptance model (PAM). PURPOSE: Despite significant previous research on health apps, few studies have focused on the post-adoption behaviors of using these technologies. To address and fill the gaps in health app research, this study has developed and tested a model to explain the micro-mechanism that determines the continuance intention to use health apps, theoretically relying on the post-acceptance model (PAM) and the technology acceptance model (TAM). METHODS: A sample consisting of 343 Korean adults who were currently using health apps on smartphones participated in an online survey. A path analysis was conducted to test the proposed model composed of the main factors from PAM and TAM. RESULTS: The results from the path analysis indicated that the following perceptual and emotional factors-perceived usefulness, perceived ease of use, confirmation, and satisfaction-were significantly associated with the continuance intention to use health apps on smartphones. DISCUSSION/CONCLUSION: Main findings from this present study contribute to developing and empirically testing a model of explaining the basic process of motivating health app users to keep using those apps. This model will be helpful for researchers to further examine health-related technologies, particularly mHealth-oriented ones. PMID- 26806715 TI - Attitudes toward medical and genetic confidentiality in the Saudi research biobank: An exploratory survey. AB - Achieving a balance between giving access to information and respecting donors' confidentiality is a crucial issue for any biobank, with its large number of samples and associated information. Despite the existence of much empirical literature on confidentiality, there are too few surveys in the Middle East about the topic, particularly in the Saudi context. A survey was conducted of 200 respondents at King Abdulaziz Medical City in Riyadh, Saudi Arabia, among 5 groups of equal size, comprised of researchers, physicians, medical students, donors and laypersons, respectively. The majority of participants agreed that confidentiality is an important issue and that it is well protected in the Saudi biobank. All 5 groups showed different attitudes toward disclosing information to various third parties. They were in favor of allowing treating physicians, and to a certain extent family members, to have access to medical and genetic results from research. No significant differences were found between views on medical and genetic confidentiality. The majority of respondents agreed that confidentiality might be breached in cases with specific justified reasons. Even considering differences in religion, culture and other factors, the results of the study were consistent with those reported in the literature and research conducted in other countries. We therefore place emphasis on the importance of protecting and promoting patient/donor confidentiality and privacy. PMID- 26806716 TI - A review of randomized controlled trials of medical record powered clinical decision support system to improve quality of diabetes care. AB - BACKGROUND: A gap between current diabetes care practice and recommended diabetes care standards has consistently been reported in the literature. Many IT-based interventions have been developed to improve adherence to the quality of care standards for chronic illness like diabetes. OBJECTIVE: The widespread implementation of electronic medical/health records has catalyzed clinical decision support systems (CDSS) which may improve the quality of diabetes care. Therefore, the objective of the review is to evaluate the effectiveness of CDSS in improving quality of type II diabetes care. Moreover, the review aims to highlight the key indicators of quality improvement to assist policy makers in development of future diabetes care policies through the integration of information technology and system. SELECTION OF STUDY: Setting inclusion criteria, a systematic literature search was conducted using Medline, Web of Science and Science Direct. Critical Appraisal Skills Programme (CASP) tools were used to evaluate the quality of studies. Eight randomized controlled trials (RCTs) were selected for the review. In the selected studies, seventeen clinical markers of diabetes care were discussed. Three quality of care indicators were given more importance in monitoring the progress of diabetes care, which is consistent with National Institute for Health and Care Excellence (NICE) guidelines. The presence of these indicators in the studies helped to determine which studies were selected for review. Clinical- and process-related improvements are compared between intervention group using CDSS and control group with usual care. Glycated hemoglobin (HbA1c), low density lipid cholesterol (LDL C) and blood pressure (BP) were the quality of care indicators studied at the levels of process of care and clinical outcome. FINDINGS: The review has found both inconsistent and variable results for quality of diabetes care measures. A significant improvement has been found in the process of care for all three measures of quality of diabetes care. However, weak to modest positive results are observed for the clinical measures of the diabetes care indicators. In addition to this, technology adoption of CDSS is found to be consistently low. CONCLUSION: The review suggests the need to conduct further empirical research using the critical diabetes care indicators (HbA1c, LDL-C and BP) to ascertain if CDSS improves the quality of diabetes care. Research designs should be improved, especially with regard to baseline characteristics, sample size and study period. With respect to implementation of CDSS, rather than a sudden change of clinical work practice, there should instead be an incremental, gradual adoption of technology that minimizes the disruption in clinical workflow. PMID- 26806717 TI - Use of a remote clinical decision support service for a multicenter trial to implement prediction rules for children with minor blunt head trauma. AB - OBJECTIVE: To evaluate the architecture, integration requirements, and execution characteristics of a remote clinical decision support (CDS) service used in a multicenter clinical trial. The trial tested the efficacy of implementing brain injury prediction rules for children with minor blunt head trauma. MATERIALS AND METHODS: We integrated the Epic((r)) electronic health record (EHR) with the Enterprise Clinical Rules Service (ECRS), a web-based CDS service, at two emergency departments. Patterns of CDS review included either a delayed, near real-time review, where the physician viewed CDS recommendations generated by the nursing assessment, or a real-time review, where the physician viewed recommendations generated by their own documentation. A backstopping, vendor based CDS triggered with zero delay when no recommendation was available in the EHR from the web-service. We assessed the execution characteristics of the integrated system and the source of the generated recommendations viewed by physicians. RESULTS: The ECRS mean execution time was 0.74 +/-0.72 s. Overall execution time was substantially different at the two sites, with mean total transaction times of 19.67 and 3.99 s. Of 1930 analyzed transactions from the two sites, 60% (310/521) of all physician documentation-initiated recommendations and 99% (1390/1409) of all nurse documentation-initiated recommendations originated from the remote web service. DISCUSSION: The remote CDS system was the source of recommendations in more than half of the real-time cases and virtually all the near-real-time cases. Comparisons are limited by allowable variation in user workflow and resolution of the EHR clock. CONCLUSION: With maturation and adoption of standards for CDS services, remote CDS shows promise to decrease time to-trial for multicenter evaluations of candidate decision support interventions. PMID- 26806718 TI - Eliciting end-user expectations to guide the implementation process of a new electronic health record: A case study using concept mapping. AB - OBJECTIVE: To evaluate the usability of concept mapping to elicit the expectations of healthcare professionals regarding the implementation of a new electronic health record (EHR). These expectations need to be taken into account during the implementation process to maximize the chance of success of the EHR. SETTING: Two university hospitals in Amsterdam, The Netherlands, in the preparation phase of jointly implementing a new EHR. During this study the hospitals had different methods of documenting patient information (legacy EHR vs. paper-based records). METHOD: Concept mapping was used to determine and classify the expectations of healthcare professionals regarding the implementation of a new EHR. A multidisciplinary group of 46 healthcare professionals from both university hospitals participated in this study. Expectations were elicited in focus groups, their relevance and feasibility were assessed through a web-questionnaire. Nonmetric multidimensional scaling and clustering methods were used to identify clusters of expectations. RESULTS: We found nine clusters of expectations, each covering an important topic to enable the healthcare professionals to work properly with the new EHR once implemented: usability, data use and reuse, facility conditions, data registration, support, training, internal communication, patients, and collaboration. Average importance and feasibility of each of the clusters was high. CONCLUSION: Concept mapping is an effective method to find topics that, according to healthcare professionals, are important to consider during the implementation of a new EHR. The method helps to combine the input of a large group of stakeholders at limited efforts. PMID- 26806719 TI - Different hydrogen isotope fractionations during lipid formation in higher plants: Implications for paleohydrology reconstruction at a global scale. AB - Leaf wax deltaDn-alkane values have shown to differ significantly among plant life forms (e.g., among grasses, shrubs, and trees) in higher plants. However, the underlying causes for the differences in leaf wax deltaDn-alkane values among different plant life forms remain poorly understood. In this study, we observed that leaf wax deltaDn-alkane values between major high plant lineages (eudicots versus monocots) differed significantly under the same environmental conditions. Such a difference primarily inherited from different hydrogen biosynthetic fractionations (epsilonwax-lw). Based upon a reanalysis of the available leaf wax deltaDn-alkane dataset from modern plants in the Northern Hemisphere, we discovered that the apparent hydrogen fractionation factor (epsilonwax-p) between leaf wax deltaDn-alkane values of major angiosperm lineages and precipitation deltaD values exhibited distinguishable distribution patterns at a global scale, with an average of -1400/00 for monocotyledonous species, -1070/00 for dicotyledonous species. Additionally, variations of leaf wax deltaDn-alkane values and the epsilonwax-p values in gymnosperms are similar to those of dicotyledonous species. Therefore, the data let us believe that biological factors inherited from plant taxonomies have a significant effect on controlling leaf wax deltaDn-alkane values in higher plants. PMID- 26806721 TI - Differential effect of elevated intralabyrinthine pressure on ocular vestibular evoked myogenic potentials elicited by air conducted sound and bone conducted vibration. PMID- 26806722 TI - Orthostatic hypertension: An underestimated cause of orthostatic intolerance. AB - OBJECTIVE: To investigate the frequency and mechanism of orthostatic hypertension (OHT) in patients with orthostatic intolerance. METHODS: We retrospectively reviewed 1033 consecutive case series of orthostatic intolerance that underwent autonomic function tests including a head-up tilt test. OHT was defined as a paradoxical orthostatic increase in systolic blood pressure (BP) of at least 20 mmHg during the tilt. We collected autonomic parameters during the standardized autonomic function tests, which included the beat-to-beat derived hemodynamic parameters during the tilt table test and compared them with age and sex-matched normal controls and the orthostatic hypotension (OH) group with orthostatic symptoms. RESULTS: We identified 38 (3.7%) patients who showed OHT during the tilt. The increase in mean systolic BP during the tilt was 26.5 mmHg. Approximately 87% (33/38) of the OHT patients showed an increase in total peripheral resistance during the tilt. The mean increase in total peripheral resistance from a supine baseline was significantly higher in OHT patients compared to normal controls, but the OH group showed a decrease in mean total peripheral resistance during the tilt. CONCLUSION: A select few patients with orthostatic dizziness can show OHT during the tilt and they have signs of increased peripheral resistance. SIGNIFICANCE: OHT may be considered in the differential diagnosis of orthostatic intolerance. PMID- 26806720 TI - Macrophages: Key regulators of steady-state and demand-adapted hematopoiesis. AB - Hematopoietic stem cell (HSC) function is required for balanced blood production throughout life; it is thus essential to understand the mechanisms regulating this highly dynamic process. Bone marrow-resident macrophages (Mphis) have recently emerged as an important component of the HSC niche, where they contribute to regulating HSC and progenitor cell (HSPC) mobilization and function. Here we review the role of macrophages (Mphis) on immune cell production, HSPC pool size, and mobilization at steady state and under inflammatory conditions. Inflammation induces marked changes in hematopoiesis to restrict or promote generation of specific cell lineages, and this often has a negative impact on HSC function. Cytokines and growth factors induced during inflammation influence hematopoiesis by acting directly on HSPCs and/or by modulating niche cell function. We focus particular attention on the opposing effects of two key inflammatory proteins, interferon-gamma and granulocyte-colony stimulating factor, in regulating bone marrow-resident macrophages (Mphis) and HSPCs. Macrophages (Mphis) are essential for tissue homeostasis, and here we highlight their emerging role as a central regulator of both steady-state and demand-adapted hematopoiesis. PMID- 26806723 TI - Development and use of microsatellite markers to study diversity, reproduction and population genetic structure of the cereal pathogen Ramularia collo-cygni. AB - Ramularia collo-cygni (Rcc) is a major pathogen of barley that causes economically serious yield losses. Disease epidemics during the growing season are mainly propagated by asexual air-borne spores of Rcc, but it is thought that Rcc undergoes sexual reproduction during its life cycle and may also disperse by means of sexual ascospores. To obtain population genetic information from which to infer the extent of sexual reproduction and local genotype dispersal in Rcc, and by implication the pathogen's ability to adapt to fungicides and resistant cultivars, we developed ten polymorphic microsatellite markers, for which primers are presented. We used these markers to analyse the population genetic structure of this cereal pathogen in two geographically distant populations from the Czech Republic (n=30) and the United Kingdom (n=60) that had been sampled in a spatially explicit manner. Genetic diversity at the microsatellite loci was substantial, Ht=0.392 and Ht=0.411 in the Czech and UK populations respectively, and the populations were moderately differentiated at these loci (Theta=0.111, P<0.01). In both populations the multilocus genotypic diversity was very high (one clonal pair per population, resulting in >96% unique genotypes in each of the populations) and there was a lack of linkage disequilibrium among loci, strongly suggesting that sexual reproduction is an important component of the life cycle of Rcc. In an analysis of spatial genetic structure, kinship coefficients in all distance classes were very low (-0.0533 to 0.0142 in the Czech and -0.0268 to 0.0042 in the Scottish population) and non-significant (P>0.05) indicating lack of subpopulation structuring at the field scale and implying extensive dissemination of spores. These results suggest that Rcc possesses a high evolutionary potential for developing resistance to fungicides and overcoming host resistance genes, and argue for the development of an integrated disease management system that does not rely solely on fungicide applications. PMID- 26806724 TI - Impact of point-of-care international normalized ratio monitoring on quality of treatment with vitamin K antagonists in non-self-monitoring patients: a cohort study. AB - BACKGROUND: Point-of-care (POC) international normalized ratio (INR) monitoring by healthcare professionals could eliminate the need for venous blood sampling in non-self-monitoring (NSM) patients on vitamin K antagonists (VKA). However, few studies have investigated the impact of POC INR monitoring on the quality of treatment in these patients and real-world data on this issue are lacking. OBJECTIVES: To investigate the safety, efficacy and quality of anticoagulant control during POC INR monitoring as compared with laboratory INR monitoring in NSM patients. METHODS: We performed a retrospective cohort study using data from the anticoagulation clinic of the Star-Medical Diagnostic Center (Rotterdam, the Netherlands). Patients who received treatment with VKA between 29 May 2012 and 29 May 2014 were eligible. Percentage of time in therapeutic range (TTR) and incidence rates of major clinical events (all-cause mortality, hospitalization, major bleeding and ischemic stroke) were compared for the year before and year after introduction of POC monitoring. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals for major clinical events between exposure groups. RESULTS: In total, 1973 patients during the 1-year laboratory-monitoring observation period and 1959 patients during the 1-year POC monitoring observation period were included. Median TTR was significantly lower during POC monitoring (77.9%; 95% CI, 67.2-87.4) than during laboratory INR monitoring (81.0%; 95% CI, 71.1-90.5). Adjusted hazard ratios for major clinical events were all around unity. CONCLUSIONS: Although associated with lower TTR, POC INR monitoring is a safe and effective alternative to laboratory INR monitoring in NSM patients on VKA. PMID- 26806725 TI - Sorbitan sesquioleate; a rare cause of contact allergy in consecutively patch tested dermatitis patients. AB - BACKGROUND: Sorbitan sesquioleate (SSO) has been added to fragrance mix I (FM I) as an emulsifier since the 1990s. Being a contact allergen itself, SSO has the potential to cause false-positive reactions to FM I. Recent results obtained with selected FM I-positive patients have shown that 5% have concomitant positive reactions to SSO. OBJECTIVES: To investigate the 5-year prevalence of contact allergy to SSO and evaluate the importance of SSO allergy when patch test results for FM I are interpreted. METHODS: This was a retrospective database study of consecutively patch tested eczema patients (n = 4,637) from 2010 to 2014. All patients were tested with our baseline series including FM I and SSO 20% in pet. RESULTS: Sensitization to SSO was identified in 9 (0.2%) patients. The proportion of FM I-positive patients with concomitant positive reactions to SSO was 1.4%. CONCLUSIONS: SSO is a rare cause of contact allergy, with a 5-year prevalence of 0.2% in consecutively tested patients. Contact allergy to the emulsifier does not play a major role when the overall frequency of contact allergy to FM I is evaluated. However, to correctly diagnose individual patients, concomitant patch testing with FM I and SSO is encouraged. PMID- 26806726 TI - Preoperative predictors of adherence to multidisciplinary follow-up care postbariatric surgery. AB - BACKGROUND: Long-term multidisciplinary care after bariatric surgery is important for weight maintenance and management of co-morbidities. Despite this, the rate of attendance to follow-up appointments is universally low. OBJECTIVE: To identify patient factors that contribute to adherence to follow-up care after bariatric surgery. SETTING: Three university-affiliated hospitals in Canada METHODS: A cohort study of 388 patients who underwent bariatric surgery from January 2011 to December 2011 was performed. This program mandates multidisciplinary follow-up care at 3, 6, and 12 months, and annually thereafter. Patients' socioeconomic, psychosocial, and medical and psychiatric co-morbidities were recorded prospectively. Adherence to follow-up care was defined as having attended the majority of clinic visits (3 or 4 out of 4); all other patients were considered nonadherent. RESULTS: The mean age of patients was 45.0 years, 81.2% were female, and the majority underwent a gastric bypass (91.8%) versus a sleeve gastrectomy (8.2%); 62.1% of patients were adherent to follow-up appointments. Patients older than 25 years had a higher adherence rate than those who were younger (63.2% versus 37.5%, P = .040). Patients with full-time or part-time employment had a significantly higher adherence rate than those who were unemployed or retired (65.6% versus 50.0%, P = .017, odds ratio 1.9). Patients with obstructive sleep apnea (OSA) before surgery had higher follow-up adherence than those without OSA (62.2% versus 37.8%, P = .044). In multivariate analysis, employment remained an independent predictor of follow-up adherence (P = .017). CONCLUSION: Employment was the strongest predictor of attendance to follow-up clinic. Patients with OSA and older patients were also more likely to return consistently for scheduled follow-up. PMID- 26806727 TI - Long-term results after laparoscopic sleeve gastrectomy in a large monocentric series. AB - BACKGROUND: Laparoscopic sleeve gastrectomy (SG) has gained great popularity as a stand-alone bariatric procedure because short- and mid-term outcomes in terms of weight loss and resolution of co-morbidities have been very positive. However, long-term results from large series still are sparse. OBJECTIVES: To evaluate the long-term clinical outcomes of SG in a large series of patients undergoing SG as a stand-alone procedure. SETTING: University hospital in Italy. METHODS: A retrospective analysis of prospectively collected data from 182 patients undergoing SG between 2006 and 2008 in the authors' institution. Long-term outcomes at 6 and 7 years were analyzed in terms of weight loss and co morbidities resolution. RESULTS: Mean initial body mass index (BMI) was 45.9+/ 7.3 kg/m(2). Major postoperative complications occurred in 8 patients (5.4%): 4 leaks, 2 bleeding, 1 abdominal collection, and 1 dysphagia. All complications were managed conservatively. One hundred forty-eight patients (81.4%) completed the 72-month (6-year) follow-up. Thirty-seven patients (25%) reached a follow-up of 84 months. At year 6 follow-up the mean BMI and the mean percentage of excess weight loss (%EWL) were 30.2 kg/m(2) and 67.3%, respectively. Mean total body weight loss was 44.9 kg, while a %EWL >50 was registered in 123 patients (83.1%). Preoperative BMI did not significantly influence postoperative %EWL. Remission of type 2 diabetes mellitus, arterial hypertension, obstructive sleep apnea syndrome, and gastroesophageal reflux disease symptoms occurred in 83.8%, 59.7%, 75.6%, and 64.7% of patients, respectively. CONCLUSION: %EWL and resolution of co morbidities appear to be sustained 6 and 7 years after SG. Preoperative BMI is not predictive for weight loss outcomes. PMID- 26806729 TI - Comment on: Comparative physiogenomic analyses of weight loss in response to two modes of bariatric surgery: demonstration with candidate neuropsychiatric and cardiometabolic genes. PMID- 26806728 TI - Influence of diet and supplements on iron status after gastric bypass surgery. AB - BACKGROUND: Iron deficiency is common after Roux-en-Y gastric bypass (RYGB) surgery, but there is no consensus on the optimal diet quality and quantity for restoring and preserving iron status. OBJECTIVES: The authors explored the impact of dietary and supplemental sources of iron and absorptive factors on iron status. SETTING: Academic, United States. METHODS: In a cross-sectional cohort of individuals who underwent RYGB, nutrient intakes from food and supplements were measured using 3-day food records. Blood biomarkers of iron status, including concentrations of ferritin, total iron binding capacity, serum transferrin receptor (sTfR), and the sTfR:ferritin ratio, were assessed by a reference laboratory; iron deficiency was defined as having at least 2 abnormal measures. Associations between iron status biomarkers and dietary predictors were determined using regression analysis. RESULTS: Of the 36 participants, 97% were female, the mean age was 45 years (95% confidence interval, 41-48 years), and body mass index was 32 (30-35) kg/m(2). Iron deficiency was found in 42% of participants. Dietary intake of heme iron, found in meats, was favorably associated with 3 iron status biomarkers (ferritin, beta = .366; sTfR:ferritin ratio, beta = -.459; and total iron binding capacity, beta = -18.26; all P<.05), independent of obesity-induced inflammation. Intake of vitamin C from food contributed to iron status (ferritin, beta = .010 and sTfR:ferritin ratio, beta = -.011; P<.05). Use of supplementary non-heme iron, at doses recommended for prophylaxis (45 mg/d), was positively associated with serum ferritin (beta = .964; P = .029). CONCLUSIONS: For patients who have undergone RYGB, consuming high, but realistic amounts of heme iron in meat, vitamin C from food, and adherence to recommended iron supplements can prevent iron deficiency. PMID- 26806730 TI - Equol protects PC12 neuronal cells against hypoxia/reoxygenation injury in vitro by reducing reactive oxygen species production. AB - OBJECTIVE: Both of gp91(phox) (an isoform of nicotinamide adenine dinucleotide phosphate-reduced oxidases) and Src (a non-receptor protein tyrosine kinase) play a prominent role in mediating hypoxia/reoxygenation injury of neurons. The present study was designed to investigate the neuroprotective effect of equol, a predominant active metabolite of daidzein, against hypoxia/reoxygenation injury in rat pheochromocytoma cell line (PC12) and explore the underlying mechanisms. METHODS: PC12 cells exposed to hypoxia/reoxygenation injury were examined for reactive oxygen species (ROS) using dihydroethidium and 2', 7' dichlorofluorescein diacetate and analyzed for changes in lactate dehydrogenase (LDH) activity and malondialdehyde (MDA) content. The expression levels of gp91(phox) and phosphorylated Src-Tyr416 (p-Src) were measured using Western blotting. RESULTS: Equol dose-dependently restored the cell viability and decreased LDH activity and MDA content in culture medium of PC12 cells exposed to hypoxia/reoxygenation. Pretreatment of the cells with 10(-5) and 10(-6) mol/L equol inhibited hypoxia/reoxygenation-induced increase of ROS. PC12 cells treated with equol prior to hypoxia/reoxygenation injury showed significant enhancement of the protein levels of gp91(phox) and p-Src. CONCLUSION: Equol confers neuroprotection against hypoxia/reoxygenation injury in PC12 cells by inhibiting the generation of ROS very likely as a result of down-regulation of gp91(phox) and inhibition of Src phosphorylation. PMID- 26806731 TI - [Role of nuclear factor of activated T cells-2 in high mobility protein box-1 release in human monocytic THP-1 cells in vitro]. AB - OBJECTIVE: To investigate the role of nuclear factor of activated T cells -2 (NFAT2) in release of high mobility protein box-1 (HMGB1) from human monocytic THP-1 cells in vitro. METHODS: The level of HMGB1 release from THP-1 cells in response to lipopolysaccharide (LPS) stimulation was examined by Western blotting and enzyme-linked immunosorbent assay (ELISA). The effect of LPS stimulation on NFAT2 and HMGB1 interaction in the cytoplasm was observed by immunoprecipitation assay. HMGB1 production and release was detected in cells with specific small interfering RNA (siRNA)-mediated suppression of NFAT2 expression. RESULTS: LPS stimulated HMGB1 release from THP-1 cells. As LPS stimulation prolonged, HMGB1 concentration increased in the cell culture supernatant and decreased in the cytoplasm, and the binding between NFAT2 and HMGB1 was not detected in the cell nuclei. NFAT2 suppression by the siRNA plasmid resulted in increased HMGB1 level in the cell culture supernatant. CONCLUSION: NFAT2 can inhibit HMGB1 release from THP-1 cells in vitro. PMID- 26806732 TI - [Annular electrode lacrimal duct reconstruction for improving the safety and efficacy of lacrimal stent implantation: a randomized clinical trial]. AB - OBJECTIVE: To evaluate the effect of annular electrode lacrimal duct reconstruction in improving the safety and efficacy of nasolacrimal duct stent implantation for treatment of nasolacrimal duct obstruction. METHODS: This randomized clinical trial was performed to compare the efficacy, success rate of intubation, time used for stent implantation, intraoperative pain, and extubation assciated complications between nasolacrimal stent implantation with and without annular electrode lacrimal duct reconstruction. RESULTS: A total of 119 eligible patients were enrolled in this trial. The total curative rate at 6 months of follow up after extubation was 70.9% (83/117) in these patients, and was significnatly higher in pateinets with lacrimal duct reconstruction than in those without [80.6% (54/67) vs 58.0% (29/50); chi(2)=7.093, P<0.05]. The total success rate of stent implantation was 98.3% (117/119) in all the patients initially enrolled, and two patients experienced failure of stent implantation and were excluded; the success rate was signfiicantly higher in patients initially enrolled in the lacrimal duct reconstruction group (chi(2)=6.282, P<0.05). The median time required for intubation was shorter in lacrimal duct reconstruction group (12 s vs 33 s; Z=-36.722, P<0.05). The intendity of intraoperative pain was comparable between the two groups (t=0.833, P=0.405). The total rate of puncta injury was 43.6% (51/117) in these patients and similar between the two groups (chi(2)=1.459, P=0.227). The total rate of extubation difficulty was 9.4% (11/117) in all the patients, and was lower in lacrimal duct reconstruction group [4.5% (3/67) vs 16% (8/50); chi(2)=4.463, P<0.05]. Stent breakage in extubation occurred in 4.3% (11/117) of the patients with similar rates between the two groups (chi(2)=2.964, P=0.085). Spearman bivariate correlation analysis showed that the time required for intubation was inversely correlated with the treatment efficacy (r=-0.584, P<0.05) and positively with the occurrence of extubation difficulty (r=0.491, P<0.05); extubation difficulty was inversely correlated with the curative effect (r=-0.511, P<0.05). CONCLUSION: Annular electrode nasolacrimal duct reconstruction can increase the safety and efficacy of nasolacrimal duct stent implantation for treatment of nasolacrimal duct obstruction. PMID- 26806733 TI - [Establishment of a diet-induced obesity model in zebrafish larvae]. AB - OBJECTIVE: To establish a diet-induced obesity model in zebrafish larvae. METHODS: At 7 days post-fertilization (dpf), 200 zebrafish larvae with normal development were randomly allocated to two groups with the feeding quantity of 30 mg per day (normal feeding group) or 180 mg per day (overfed group) for 20 days. The weight, length, BMI, triglyceride (TG) and total cholesterol (TCH) of each group were measured. Whole-mount Oil Red O staining, frozen Oil Red O staining and hematoxylin-eosin (HE) staining were used to estimate the rate of hepatic steatosis and liver histology of the zebrafish. The dynamic change of hepatic lipid droplets and distribution of adipose tissue were observed with Nile Red staining in overfed zebrafish in vivo. RESULTS: The weight, length, BMI and TG of overfed zebrafish were significantly increased compared with those in normal feeding group. Whole-mount Oil Red O staining showed that the percent of hepatic steatosis in overfed group (89.4%) was markedly higher than that in normal feeding group (20.7%). Macrovesicular steatosis was observed in the liver of the overfed larvae. Nile Red staining visualized hepatic lipid droplets and the distribution of larval adipose tissue, which increased with feeding time in the overfed zebrafish. Starving larvae showed depletion of fat and hepatic lipid, and adipose tissue was induced after refeeding. CONCLUSIONS: We successfully established an diet-induced obesity model in zebrafish larva, in which Nile Red staining allows in vivo observation of the adipocytes and hepatic lipid droplets. PMID- 26806734 TI - [Three-dimensional classification of the right portal vein and liver segmentation based on three-dimensional visualization technology]. AB - OBJECTIVE: To investigate the anatomy of right portal vein based on three dimensional (3D) visualization technology and provide a morphological basis for computer-assisted individualized liver segmentation and anatomical hepatectomy. METHODS: Liver CT data of 83 cases were segmented and reconstructed using the medical image three-dimensional visualization system (MI-3DVS), and 3D classifications of the right portal vein were established according to its branch number, direction and distribution. Individualized liver segmentation was performed based on the 3D typing results. RESULTS: The reconstructed portal vein models were capable of visualizing the fourth-order portal branches. Generally, the third-order right portal branches were classified into P5, P6, P7 and P8 branches. According to the 3D distribution of the branches, P5 branches were classified into types A, B, C, D, and E [in 16 (19.3%), 5 (6%), 30 (36.1%), 7(8.5%), and 25 (30.1%) cases, respectively], P8 branches into types A, B, C, and D [in 29 (34.9%), 29 (34.9%), 10 (12.1%), and 15 (18.1%) cases, respectively], P6 branches into types A, B, C, and D [in 35 (42.2%), 12 (14.5%), 33 (39.7%), and 3 (3.6%) cases, respectively], and P7 branches into types A, B, C, D, E, and F [in 27 (32.5%), 11(33.3%), 27 (32.5%), 4(4.8%), 12 (14.5%), and 2 (2.4%) cases, respectively]. Individualized liver segmentation was achieved based on liver segments supplied by the third-order portal branches. CONCLUSION: 3D classifications of the complex and highly variant anatomy of third-order right portal vein and individualized liver segmentation based on this classification before the operation facilitates successful performance of anatomical hepatectomy. PMID- 26806735 TI - [Therapeutic effect of GDNF gene-modified mesencephalic neural stem cell transplantation in a rat model of Parkinson disease]. AB - OBJECTIVE: To evaluate the therapeutic effect of transplantation of mesencephalic neural stem cells (mNSCs) genetically modified by glial cell line-derived neurotrophic factor (GDNF) gene in a rat model of Parkinson disease. METHODS: mNSCs isolated from the lateral component of the midbrain of fetal rats at gestational age of 14 or 15 days were cultured for 5 days before genetic modification with GFP or GDNF gene. Rat models of Parkinson disease established by stereotactic injection of 6-hydroxy dopamine in the ventral area of the midbrain and the medial forebrain bundle were randomized into 3 groups to receive PBS injection, GFP gene-modified mNSCs transplantation, or GDNF gene-modified mNSCs transplantation into the right stratum. The behavioral changes of the rats were evaluated by observing rotations induced by intraperitoneal injection of apomorphine after the transplantation, and the survival, migration and differentiation of the transplanted cells were identified by immunohistochemistry. RESULTS: Transplantation with GDNF gene-modified mNSCs significantly improved the behavioral abnormalities of the rat models as compared with PBS injection and GFP gene-modified mNSCs transplantation. At 56 days after the transplantation, a greater number of the transplanted cells survived in the rat brain and more differentiated dopaminergic neurons were detected in GDNF gene modified mNSCs transplantation group than in GFP gene-modified mNSCs transplantation group. CONCLUSION: GDNF gene-modified mNSCs transplantation can significantly improve dyskinesia in rat models of Parkinson disease, but the molecular mechanism needs further clarification. PMID- 26806736 TI - [Low-dose methotrexate combined with vinorelbine for inoperable desmoid tumor: efficacy and the prognostic factors]. AB - OBJECTIVE: To characterize the clinical features of desmoid tumor, assess the efficacy of conservative chemotherapy for inoperable desmoid tumor and analyze the prognostic factors. METHODS: From August 2009 to December 2013, 52 patients with inoperable desmoid tumor were treated in our department and received chemotherapy with vinorelbine combined with low-dose methotrexate. The clinical data of the patients were analyzed retrospectively. RESULTS: The patients studied included 22 male and 30 female patients with the age of disease onset ranging from 2 to 46 years (mean 18.7 years). The lesions occurred most frequently in the lower limbs (36.5%, 19/52) and the tumor size ranged from 2.7 to 37 cm (mean 9.5 cm). The patients were followed up for a median of 29 months (7 to 64 months). The chemotherapy lasted for 4 to 30 months (median 12 months). After completion of the chemotherapy, 1 patient had a complete response (CR), 18 showed partial responses (PR), 27 cases had stable disease (SD), and 6 had progressive disease (PD), with an overall response rate (ORR) of 88.5%. The progression-free survival (PFS) time of the patients ranged from 4 to 63 months (median 26.5 months) with a 2-year PFS rate of 76.7% and 5-year PFS rate of 41.9%. A longer chemotherapy duration (over 12 months) was associated with a more favorable prognosis. No significant differences in PFS were found between the patients stratified by gender, age of disease onset, age when receiving chemotherapy, tumor site, or tumor size. CONCLUSION: For recurrent, inoperable and progressive desmoid tumor, long enough cycles of vinorelbine combined with low-dose methotrexate can be an effective and safe option for tumor control. PMID- 26806737 TI - [Occupational, educational and residential factors are associated with the outcomes of in vitro fertilization-embryo transfer]. AB - OBJECTIVE: To investigate the associations of occupational, educational and residential factors with the outcomes of in vitro fertilization -embryo transfer (IVF-ET). METHODS: A retrospective analysis was conducted among 3998 patients undergoing the first treatment with IVF-ET and 3064 perinatal infants in our center between January, 2010 and June, 2014. The relation of the patients' occupation, educational background, and residence registry with IVF-ET outcomes was analyzed. RESULTS: The risk of abortion in the first trimester was significantly higher in female patients engaged in agriculture (OR=4.319, P=0.047). Occupation and educational background of the patients and their spouse were related with the incidence of ectopic pregnancy following IVF-ET. The total incidence rate of perinatal birth defects was 2.1% in this cohort, and was the highest in Shenzhen (5.5%) but this difference was not statistically significant (P>0.05). CONCLUSION: The patients' occupation and educational background are related with the outcomes of IVF-ET, suggesting the importance of health education and prenatal examination. PMID- 26806738 TI - [Expressions of SMG-1, ATM and P53 in laryngeal squamous cell carcinoma and their clinical significance]. AB - OBJECTIVE: To detect the expression of SMG-1, ATM and P53 in laryngeal squamous cell carcinoma (LSCC) and their correlation with the clinicopathological features and outcomes of the patients. METHODS: Sixty-three specimens of surgically resected LSCC tissues and 30 specimens of adjacent normal tissue were examined for the expressions of ATM, SMG-1 and P53 using immunohistochemistry. The correlation of ATM, SMG-1 and P53 expressions with the clinicopathological factors and their interactions were analyzed. RESULTS: The positive expression rates of SMG-1, ATM and P53 in LSCC were 36.5% (23/63) , 41.3% (26/63) and 57.1% (36/63) respectively, significantly different from those in the adjacent tissue (73.3%, 83.3% and 20.0%, respectively; P<0.05). The expression of SMG-1 in LSCC was positively correlated with the pathological grade and T stage of the tumors (P<0.05), and ATM and P53 were not related to the clinicopathological factors (P>0.05). The 5-year survival rate of patients negative for SMG-1 expression was significantly higher than that of SMG-1-positive patients (P<0.05). The expression of SMG-1 was negatively correlated with that of P53 (r=-0.476, P<0.01). CONCLUSION: SMG-1, ATM and P53 are closely related to the occurrence of LSCC. SMG-1 expression is an important factor associated with the clinicopathological features and prognosis of LSCC patients, and may play an important role in the development of LSCC by regulating P53 expression. PMID- 26806739 TI - [Cabozantinib inhibits Listeria monocytogenes infection in mice]. AB - OBJECTIVE: To test the effect of the c-Met inhibitor cabozantinib in inhibiting infections by Listeria monocytogenes (LM) in mice. METHODS: C57BL/6 mice at 6 weeks of age were subjected to intraperitoneal injection of LM and randomized into 4 groups for treatment with intraperitoneal injection of PBS, intragastric administration of cabozantinib (20 ug/g), intraperitoneal injection of ampicillin (Amp, 20 ug/g), or cabozantinib plus Amp. The survival curves were drawn for each group, and the number of bacteria in the blood and brain tissues was determined; serum IL-10 level and NF-kappaB p65 level in the cerebrospinal fluid (CSF) were assayed, and Evans Blue (EB) content and pathological changes in brain were examined. RESULTS: Compared with PBS-treated mice, the mice treated with cabozantinib showed a significantly higher survival rate, lower bacterial counts in the blood and brain (P<0.05 or 0.001), lower IL-10 (P<0.05) and NF-kappaB p65 levels (P<0.01), lower brain EB content (P<0.001), and milder pathological changes in the brain. The blood and brain bacterial counts (P<0.001), IL-10 (P<0.01) and NF-kappaB p65 levels (P<0.001), and brain EB content (P<0.001) were all significantly lower in mice treated with the combination of drugs than in mice treated with cabozantinib alone. CONCLUSION: Cabozantinib can inhibit LM infection in mice and has important values in developing new anti-intracellular infection drug. PMID- 26806740 TI - [Automatic segmentation of lung fields in chest radiographs based on dense matching of local features]. AB - OBJECTIVE: Accurate segmentation of lung fields in chest radiographs (CXR) is very useful for automatic analysis of CXR. In this work, we propose to use dense matching of local features and label fusion to automatically segment the lung fields in CXR. METHODS: For an input CXR, the dense Scale Invariant Feature Transform (SIFT) descriptors and raw image patches were extracted as the local features for each pixel. The nearest neighbors of the local features were then quickly searched by dense matching directly from the whole feature dataset of the reference images. The dense matching included three steps: limited random initialization, propagation of nearest neighbor field, and limited random search, with iteration of the last two steps for several times. The label image patches for each pixel were extracted according to the nearest neighbor field and weighted by the matching similarity. Finally, the weighted label patches were rearranged as the label class probability image of the input CXR, from which thresholds were obtained for segmentation of the lung fields. RESULTS: The Jaccard index of the proposed method reached 95.5% on the public JSRT dataset. CONCLUSION: A high accuracy and robustness can be obtained by adopting dense matching of local features and label fusion to segment the lung fields in CXR, and the result is better than that of current segmentation method. PMID- 26806741 TI - [Rapid selection of recombinant orf virus expression vectors using green fluorescent protein]. AB - OBJECTIVE: To construct a universal, highly attenuated orf virus expression vector for exogenous genes using green fluorescent protein (GFP) as the reporter gene. METHODS: The flanking regions of the ORFV132 of orf virus DNA were amplified by PCR to construct the shuttle plasmid pSPV-132LF-EGFP-132RF. The shuttle plasmid was transfected into OFTu cells and GFP was incorporated into orf virus IA82Delta 121 by homologous recombination. The recombinant IA82Delta121-V was selected by green fluorescent signal. The deletion gene was identified by PCR and sequencing. The effects of ORFV132 knockout were evaluated by virus titration and by observing the proliferation of the infected vascular endothelial cells in vitro. RESULTS: The recombinant orf virus IA82Delta121-V was obtained successfully and quickly, and the deletion of ORFV132 did not affect the replication of the virus in vitro but reduced its virulence. CONCLUSION: Green fluorescent protein is a selectable marker for rapid, convenient and stable selection of the recombinant viruses. Highly attenuated recombinant orf virus IA82Delta121-V can serve as a new expression vector for exogenous genes. PMID- 26806742 TI - [Role of platelet-activating factor receptor in adhesion and invasion of Aggregatibacter actinomycetemcomitans in human umbilical vein endothelial cells]. AB - OBJECTIVE: To explore the role of platelet-activating factor receptor (PAFR) in adhesion and invasion of phospho- rylcholine (PC)-positive Aggregatibacter actinomycetemcomitans in cultured human umbilical vein endothelial cells (HUVEC). METHDOS: Cultured HUVECs were pretreated with the PAFR antagonist CV3988 or anti human PAFR monoclonal antibody for 30 min before infection with PC-positive or negative A. actinomycetemcomitans strains. The bacterial adhesion and invasion and cytotoxicity in the cells were examined using MTT assay. RESULTS: Pretreatment with PAFR antagonists at 100, 200 and 500 nmol/L significantly reduced the adhesion rate (36.29?3.52)%, (19.04?3.35)% and (7.69?3.19%), respectively] and invasion rate [(12.12?1.58)%, (7.08?0.29)% and (2.60?2.26)%, respectively] of PC-positive A.actinomycetemcomitans in HUVECs. Similarly, pretreatment with anti-PAFR antibody also significantly reduced A.actinomycetemcomitans adhesion and invasion in HUVECs [(50.05?5.28)% and (39.09?6.50)%, respectively]. Pretreatment with PAFR antagonist (200 and 500 nmol/L) and anti-PAFR antibody (25 ug/mL) significantly increased the viability of HUVECs incubated with PC-positive A.actinomycetemcomitans from (25.39?9.33)% to (91.12?3.14)%, (94.12?2.15)% and (65.5?1.87)%, respectively, but such pretreatments did not increase the viability of cells incubated with PC-negative A.actinomycetemcomitans. CONCLUSIONS: PAFR plays an important role in the adhesion, invasion, and cytotoxicity of PC-positive A.actinomycetemcomitans in cultured HUVECs. PMID- 26806743 TI - [Tal1 promotes proliferation of acute lymphoblastic leukemia Jurkat cells in vitro]. AB - OBJECTIVE: To investigate the role of Tal1 gene, which is aberrantly expressed in 40%-60% of patients with T lymphocytic leukemia (T-ALL), in the proliferation of T-ALL cells. METHODS: We established stable Jurkat-siTal1 and Jurkat-T1 cell lines by trasnfecting T-ALL Jurkat cells with lentiviral vectors to knock-down or overexpress Tal1. Jurkat cells transfected with negative control siRNAs for Tal1 knock-down (Jurkat-mock1) and over-expression(Jurkat-mock2) served as the control cells. The proliferation of the cells lines was assessed using CCK-8 assay, and the cell cycle distribution was determined by flow cytometry. The mRNA and protein expressions of cyclin-dependent kinase inhibitor 2 (CDKN2A) and cyclin dependent kinase inhibitor 1 (CDKN2B) were measured by real-time RT-PCR and Western blotting, respectively. RESULTS: Jurkat-T1 cells showed more active proliferation in vitro than Jurkat-mock2 cells, while Jurkat-siTal1 cells showed slower growth than Jurkat-mock1 cells. In Jurkat-T1 cells, G0/G1 phase cells were decreased and S phase cells increased compared with Jurkat-mock2 cells, and Jurkat-siTal1 cells showed increased G0/G1 phase cells and decreased S phase cells compared with Jurkat-mock1 cells. Real-time RT-PCR and Western blotting showed that Tal1 inhibited the cellular expression of CDKN2A and CDKN2B at both mRNA and protein levels. CONCLUSION: Tal1 promotes the growth and the transition from G0/G1 phase to S phase in T-ALL cells Jurkat by inhibiting the expressions of G0/G1 and S phase negative regulatory proteins CDKN2A and CDKN2B. PMID- 26806744 TI - [Correlation between waist circumference and organ damage in patients with cardiovascular disease after cardiac rehabilitation program]. AB - OBJECTIVE: To clarify the role of waist circumference (WC) in estimating organ damage and assessing the prognosis in young and middle-aged patients with cardiovascular disease undergoing cardiac rehabilitation program (CRP). METHODS: We recruited 147 young and middle-aged patients with cardiovascular disease to participate in the CRP for 4 or 5 weeks. The baseline clinical data and results of routine fasting blood test and ultrasonic cardiography were evaluated for these patients. RESULTS: WC had a linear correlation with the indices reflecting cardiac structure alteration (LVSd and LVPWd) of the patients after CRP but showed a negative correlation with their HDL-C levels. The fasting blood glucose (FBG) and serum uric acid (UA) levels showed a positive correlation with WC before CRP but not after CRP. CONCLUSION: WC monitoring allows accurate assessment of organ damage in patients undergoing CRP after cardiovascular disease and has special value in evaluating the changes in cardiac structure and function. PMID- 26806745 TI - [Pharmacokinetics and bioequivalence assessment of a self-assembled asparaginase nanocapsule in rats]. AB - OBJECTIVE: To study the pharmacokinetics and bioequivalence of asparaginase loaded in hyaluronic acid-graft-poly(ethylene glycol)/ sulfobutylether-beta cyclodextrin nanocapsules (AHSP) in SD rats. METHODS: The morphology of AHSP was observed under the transmission electron microscope and the particle size and zeta potential were measured. AHSP and free asparaginase were intravenously injected in rats, and the plasma asparaginase activity was measured at different time points after the injections. The pharmacokinetic parameters were calculated using the software DAS 2.1.1 to assess the bioequivalence of AHSP and free asparaginase. RESULTS: AHSP had an average particle size of 413.80?10.97 nm with a zeta potential of -20.37?2.38 mV. The AUC(0-48 h) of AHSP and free asparaginase was 137.34?1.82 U/mL and 46.38 ?1.98 U/mL, and their AUC(0-infinity) was 164.66?6.88 U/mL and 51.44?3.01 U/mL with half-lives of 4.62?0.60 h and 1.86?0.38 h, respectively. Compared with free AN, AHSP exhibited increased AUC(0-48 h), AUC(0-infinity), and half-life by 2.24, 2.55 and 2.32 folds, respectively. The 90% confidential intervals of AUC(0-48 h), AUC(0-infinity) and Cmax of the tested formulation were 75.0%-76.5%, 74.3%-76.1%, and 95.1%-96.7%, respectively. CONCLUSION: AHSP can improve the bioavailability and extend the biological half life of asparaginase in rats, and AHSP and free asparaginase are not bioequivalent. PMID- 26806746 TI - [Expression pattern of membrane type-1 matrix metalloproteinase in primary breast carcinomas]. AB - OBJECTIVE: To examine the expression pattern of membrane type-1 matrix metalloproteinase (MT1-MMP) in breast carcinomas. METHODS: Forty-three breast cancer tissues were collected and examined for MT1-MMP protein and mRNA expressions using immunohistochemistry, semi-quantitative RT-PCR and in situ hybridization. RESULTS: Immunohistochemistry of the breast cancer specimens showed MT1-MMP immunoreactivity on the cancer cell membrane. MT1-MMP mRNA was located in the stromal cells surrounding the breast cancer nest as shown by in situ hybridization. MT1-MMP mRNA expression was detected in all of the carcinomas, but its level was significantly lower in immunohistochemically negative specimens than in positive ones (0.547=0.0886 vs 0.759=0.0802, Plt;0.01). CONCLUSION: MT1-MMP is very likely produced by stromal cells surrounding the breast cancer nest and anchored on the cell membrane after activation. PMID- 26806747 TI - [Modulation of TLR-4/MyD88 signaling cascade by miR-21 is involved in airway immunologic dysfunction induced by cold air exposure]. AB - OBJECTIVE: To investigate the role of miR-21 in airway immunologic dysfunction induced by cold air irritation. METHODS: Immortalized human airway epithelial cell lines BEAS-2B and 16HBE cells were cultured in air-liquid phases. The differential expressions of endogenous miR-21, miR-164, and miR-155 in the cells induced by cold air exposure for different time were detected by real-time PCR. The reporter plasmid containing wild-type or mutated 3'UTR of TLR-4 were constructed and co-transfected into BEAS-2B cells or 16HBE cells together with miR-21 mimic, miR-21 mimic control, miR-21 inhibitor, or miR-21 inhibitor control. Following the transfection, dual luciferase reporter assay was performed to verify the action of miR-21 on TLR-4. miR-21 mimic, miR-21 mimic control, miR 21 inhibitor, and miR-21 inhibitor control were transfected via lipofectamine 2000 in BEAS-2B or 16HBE cells that were subsequently exposed to a temperature at 37 degrees celsius; or cold irritation (30 degrees celsius;), and the protein levels of TLR-4/MyD88 were detected by Western blotting. RESULTS: Cold irritation caused a time- dependent up-regulation of miR-21 in both BEAS-2B and 16HBE cells (P<0.05) without obviously affecting the expressions of miR-164 and miR-155. Dual luciferase reporter assay demonstrated a direct combination of miR-21 and its target protein TLR-4. The synthesis levels of TLR-4/MyD88 protein were decreased in miR-21 mimic group even at a routine culture temperature (P<0.05), as also seen in cells with cold irritation (P<0.05). Treatment with the miR-21 inhibitor partially attenuated cold irritation-induced down-regulation of TLR-4/MyD88 protein (P<0.05). CONCLUSION: Cold air irritation-induced airway immunologic dysfunction is probably associated with TLR-4/MyD88 down-regulation by an increased endogenic miR-21. PMID- 26806748 TI - [Restriction landmark genomic scanning for screening aberrant CpG methylations in prostate cancer]. AB - OBJECTIVE: To screen methylations of CpG islands in prostate cancer using restriction landmark genomic scanning (RLGS). METHODS: The DNA was extracted from homogeneous cells captured by laser capture microdissection in 20 prostate cancer and 18 benign prostatic hyperplasia (BPH) tissues for scanning the CpG islands using RLGS. The methylation status of each CpG island was compared between the cancer and BPH samples to screen the genes involved in prostate cancer development. The screened genes were uploaded to DAVID database for GO analysis, and the genes with the most significant methylation were analyzed by pyrosequencing. RESULTS AND CONCLUSION: Among all the tested CpG islands, 10245 (37.2%) in prostate cancer and 8658 (30.3%) in BPH samples were found to be abnormally methylated, and >60% of the methylated CpG islands were in the promoter region. Compared with BPH samples, the prostate cancer samples showed differential methyation in 735 CpG islands, including 458 hepermethyated and 256 hypomethelated ones. Seven genes (DPYS, P16, APC, GSTP1, TMEM122, RARB, and ARHGAP20) in prostate cancer were identified to have distinct methylations. Bioinformatics analysis suggested that these genes were associated with several biomolecular and biological processes, and among them DPYS gene was involved in 13 GO anotated biologic functions, development of 50 diseases and 47 protein interactions. Pyrosequencing of 7 sites of the CPG island in DPYS gene showed a methylation frequency of 32.7%, suggesting the importance of DPYS gene in the carcinogenesis and progression of prostate cancer. PMID- 26806749 TI - [Evaluation of in vitro insulin release from nanoparticles assembled by polyethylene glycol, polycaprolactone and polyethyleneimine]. AB - OBJECTIVE: To prepare insulin-loaded polymeric nanoparticles based on polyethyleneimine-polycaprolactone- polyethylene glycol-polycaprolactone polyethyleneimine pentablock copolymers and evaluate its in vitro release of insulin. METHODS: Polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG PCL) triblock copolymer was synthesized by ring-opening polymerization method, and the pentablock copolymer was prepared by Michael addition reaction. The copolymers obtained were characterized by Fourier-transform infrared (FT-IR) spectroscopy and (1)H-NMR and their critical aggregation concentration (CAC) was measured by fluorescence technique with pyrene as the probe. Insulin-loaded polymeric nanoparticles based on the pentablock copolymers were prepared by solvent evaporation method that exploited the cationic nature of PEI-PCL-PEG-PCL PEI to allow the formation of ionic complexes with anionic biomolecules such as insulin. The prepared nanoparticles were further characterized by Malvern laser particle sizer and transmittion electron microscopy (TEM). The drug loading, encapsulation efficiency and in vitro release profile of the nanoparticles were analyzed using Bradford method. RESULTS: Using copolymer PEI10K-PCL4K-PEG2K-PCL4K PEI10K as the drug carrier, the spherical nanoparticles prepared with an optimal insulin-coplymer mass ratio of 40% allowed the maximum insulin loading of (18.63?0.07)% and had an average particle size of 175.30?19.51 nm. The prepared nanoparticles was capable of sustained release of insulin for as long as 48 h in vitro, and the burst release could be minimized by incorporation of PEI in the triblock copolymer. CONCLUSION: The insulin-loaded polymeric nanoparticles based on the pentablock copolymers allow sustained release of insulin in vitro, and PEI can enhance sustained drug release and reduce burst drug release. PMID- 26806750 TI - [Role of p38MAPK/eNOS signaling pathway in the inhibition of AGEs-induced apoptosis of human umbilical vein endothelial cells by glucagon-like peptide-1]. AB - OBJECTIVE: To investigate the role of p38MAPK signaling pathway in the mechanism by which glucagon-like peptide-1 (GLP-1) inhibits endothelial cell damage induced by AGEs. METHODS: Human umbilical vein endothelial cells were divided into control group, AGEs group, GLP-1 group, AGEs+GLP-1 group, AGEs+inhibitor group, and AGEs+GLP-1+inhibitor group. The expressions of p-p38MAPK/p38MAPK and p eNOS/eNOS protein were examined by Western blotting, and the cell apoptosis rates were tested by flow cytometry. RESULTS: Compared with the control group, AGEs significantly enhanced the expression of p-p38 MAPK protein (P=0.001) while GLP-1 significantly inhibited its expression (P<0.001). AGEs significantly inhibited the expression of p-eNOS protein (P=0.007), which was enhanced by GLP-1 and p38 MAPK inhibitor (SB203580) (P=0.004). Both SB203580 and GLP-1 treatment decreased the apoptosis rate of AGEs-treated cells (P<0.001). CONCLUSION: GLP-1 can protect human umbilical vein endothelial cells against AGEs-induced apoptosis partially by inhibiting the phosphorylation of p38MAPK protein and promoting the expression of p-eNOS protein. PMID- 26806751 TI - [Ultrasound-guided laser thermal ablation for treatment of small liver cancer at high-risk sites]. AB - OBJECTIVE: To investigate the clinical value of ultrasound-guided laser thermal ablation (LTA) in the treatment of small liver cancer at high-risk sites. METHODS: A total of 73 lesions ablated with LTA in 68 patients with small liver cancer. After the operation, the rates of complete ablation were compared between patients with lesions of different sizes and at different sites using contrast enhanced ultrasound and the complications were recorded during the follow-up. RESULTS: The complete ablation rates for carcinomas <=1 cm, 1-2 cm, and 2-3 cm were 100%, 86.4%, and 82.7%, respectively, showing no significant differences among them (P>0.05). The complete ablation rates of lesions were similar between the high-risk and low-risk groups (85.7% vs 92.1%; P>0.05). The two groups showed no significant difference in the incidence of complications (9.1% vs 5.7%; P>0.05). CONCLUSION: Ultrasound-guided LTA can be a good option for treatment of small liver cancers at high-risk sites. PMID- 26806752 TI - [Effect of DPP4 inhibitor sitagliptin on expressions of early growth response-1 and fibronectin in the kidney of ApoE gene knockout mice]. AB - OBJECTIVE: To investigate the effects of the DPP4 inhibitor sitagliptin on the expressions of early growth response-1 (Egr-1) and fibronectin in the kidney of ApoE gene knockout mice. METHODS: Eight-week-old male ApoE gene knockout mice were randomly divided into sitagliptin + apoE(-/-) group and apoE(-/-) group (n=6), with 6 C57BL mice as the normal control group. After feeding with high-fat diet and drug treatment for 16 weeks, the mice underwent intraperitoneal glucose tolerance test (IPGTT) and were measured for 24-h urinary albumin using ELISA. All the mice were then sacrificed to examine the changes of blood lipid profile and for detection of Egr-1 and fibronectin mRNA and proteins in the renal tissue using real-time PCR and Western blotting. RESULTS: The mice in both apoE(-/-) group and sitagliptin+apoE(-/-) group all showed prominently increased blood lipids as compared with the control group (P<0.05) without significant differences between the two apoE(-/-) groups. The level of HDL was significantly higher in sitagliptin +apoE(-/-) group than in apoE(-/-) group (P<0.001) and control group (P<0.001). IPGTT showed no significant differences in the levels of blood glucose among the 3 groups. The excretion of urinary albumin was increased in apoE(-/-) group compared with the control group (P<0.01), but was significantly lower in sitagliptin+ apoE(-/-) group than in apoE(-/-) group (P<0.01). Real-time PCR and Western blotting showed significantly decreased mRNA and protein expressions of renal cortical Egr-1 and fibronectin in sitagliptin+apoE(-/-) group compared with apoE(-/-) group. CONCLUSION: Sitagliptin can reduce the renal expression of fibronectin by regulating the expression of Egr-1 to achieve renal protection. PMID- 26806753 TI - [Value of suprapubic cystostomy in bipolar transurethral resection of the prostate for benign prostatic hyperplasia below 80 gram]. AB - OBJECTIVE: To investigate the perioperative benefit of suprapubic cystostomy in bipolar transurethral resection of the prostate (B-TURP) for treatment of benign prostatic hyperplasia (BPH) below 80 g. METHODS: This retrospective study was conducted in patients undergoing B-TURP for BPH below 80 g, who were stratified with respect of suprapubic cystostomy in B-TURP. The end points including the safety, efficiency, complications and nursing care were compared between the two groups. RESULTS: A total of 585 patients were enrolled, including 366 in cystostomy group and 219 in non-cystostomy group. The two groups showed similar postoperative reduction of serum sodium (0.06 vs 0.54 mmol/L, P>0.05), hematocrict (2.44% vs 2.89%, P>0.05), and blood hemoglobin concentration (9.62 vs 10.42 g/L, P>0.05), with comparable weight of resected prostate (42.50 vs 43.76 g, P>0.05). The operation time was significantly longer in cystostomy group than in non-cystostomy group (90.75 vs 76.28 min, P<0.05), but the rate of blood transfusion and incidences of postoperative fever and catheter blocking were comparable between the two groups. Compared with the non-cystostomy group, cystostomy group had significantly longer time for bladder washing (3.15 vs 2.57 days, P<0.05), catheter indwelling time (5.19 vs 4.15 days, P<0.05), and hospital stay after the operation (7.36 vs 5.65 days, P<0.05). CONCLUSIONS: In B-TURP for BPH below the weight of 80 g, suprapubic cystostomy is associated with a longer time for operation, bladder washing, catheter indwelling and postoperative hospital stay, and thus provides no obvious benefits for the patients. PMID- 26806754 TI - [Correlation of IL-8 and IL-6 in prostatic fluid with serum prostate-specific antigen level in patients with benign prostatic hyperplasia complicated by prostatitis]. AB - OBJECTIVE: To investigate the correlation of the levels of interleukin-8 (IL-8) and IL-6 in the prostatic fluid with serum levels of serum prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH) complicated by prostatitis. METHODS: A series of 211 patients undergoing surgery of BPH were divided into BPH group (n=75) and BPH with prostatitis group (n=136) according to the white blood cell count in the prostatic fluid. The clinical and laboratory findings were compared between the two groups, and stepwise regression analysis was used to assess the association of IL-8 and IL-6 with serum PSA level. RESULTS: No significant differences were found in age, BMI, blood pressure, blood glucose, blood lipids, IPSS score, PSA-Ratio, or prostate volume between the two groups (P<0.05). The patients with prostatitis had significantly increased serum PSA and prostate fluid IL-8 and IL-6 levels compared with those without prostatitis (P<0.001). Multiple linear regression analysis showed that IL-8 and IL-6 levels and white blood cell count in the prostatic fluid were all positively correlated with serum PSA level. CONCLUSION: Prostatitis is an important risk factor for elevated serum PSA level in patients with BPH, and both IL-8 and IL-6 levels in the prostatic fluid are correlated with serum PSA level. PMID- 26806755 TI - [Impact of sperm DNA and acrosome integrity and acrosome reaction rate on outcomes of rescue intracytoplasmic sperm injection]. AB - Objective To explore the effects of sperm DNA integrity rate, acrosome integrity rate and acrosome reaction rate on the outcomes of rescue intracytoplasmic sperm injection (ICSI). METHODS: This retrospective analysis was conducted among 97 infertile couples receiving rescue ICSI due to failure of in vitro fertilization procedures in our Reproductive Medicine Center. Of these 97 women, 41 had clinical pregnancy and 56 did not, and the effects of sperm DNA integrity rate (estimated by DNA fragmentation index, DFI), acrosome integrity rate and acrosome reaction rate on rescue ICSI outcomes were analyzed. RESULTS: No significant difference was found in paternal age, testosterone value, testicular volume, FSH, female patient' age or the number of eggs retrieved between the two groups (P>0.05), but the infertility years was significantly shorter in the pregnancy group than in the non-pregnancy group (P<0.05). The fertilization rate and cleavage rate were similar between the two groups (P>0.05), but the good embryo rate was significantly higher in the pregnancy group (P<0.05). The sperm DNA integrity or acrosome reaction rate did not differ significantly between the two groups (P>0.05), but the acrosome integrity rate was significantly higher in the pregnancy group (P<0.05). The sperm DNA integrity rate, acrosome integrity or acrosome reaction rate were not correlated with the fertilization rate, cleavage rate or good embryo rate (P>0.05). The pregnancy rate, twin and single fetus rates were 42.3%, 10.3% and 32.0% in this cohort after recue ICSI, respectively. CONCLUSION: Rescue ICSI is an effective treatment after failed in vitro fertilization procedure, and sperm acrosome integrity rate is associated with the outcome of rescue ICSI. PMID- 26806756 TI - [Application of three-dimensional laparoscopic cholecystectomy for complicated gallstone disease]. AB - OBJECTIVE: To investigate the clinical value of three-dimensional (3D) laparoscopic cholecystectomy in the treatment of complicated gallstone disease. METHODS: From March 2014 to March 2015, 46 patients underwent cholecystectomy for complicated gallstone disease under 3D laparoscopy (3D group) and 43 received 2D laparoscopic cholecystectomy (2D group). The surgical data including the operative time, intraoperative blood loss, the rate of conversion to open laparotomy, recovery time of postoperative bowel motion and hospital stay were compared between the 2 groups. RESULTS: Laparoscopic cholecystectomy was successfully completed in 43 patients in 3D group and in 39 patients in 2D group, and the rates of conversion to open laparotomy were similar between the two groups (P>0.05). The median operation time was significantly shorter in 3D group than in 2D group (50.5?15.2 vs 65.4?18.1 min, P<0.05), and the median volume of intraoperative blood loss was significantly smaller in 3D group (34.1?13.6 vs 44.5?22.3 mL, P>0.05). No significant differences were found in the recovery time of postoperative bowel motion and postoperative hospital stays between the two groups (P>0.05). CONCLUSION: 3D laparoscopy, which provides three-dimensional vision with a good sense of depth to allow precise surgical manipulation, can shorten the operation time and reduce the rate of conversion to open laparotomy for patients undergoing 3D laparoscopic cholecystectomy for complicated gallstone disease. PMID- 26806757 TI - [Comparison of the effect of three-dimensional versus two-dimensional retroperitoneal laparoscopic ureter lithotomy]. AB - OBJECTIVE: To compare the surgical effect of three-dimensional (3D) versus 2D laparoscopic surgery in ureter lithotomy. METHODS: From January 2014 to 2015 May, 45 patients with ureteral calculi were randomly allocated into 2 groups to undergo ureter lithotomy under 3D laparoscopy (25 cases) and 2D laparoscopy (20 cases). The time used for each surgical process (including the exposure, D-J tube discharge, suture and other surgical procedures) was recorded and compared between the two groups. RESULTS: The operation was completed smoothly in all the 45 patients. In this cohort, the wound drainage tube was removed in a mean of 3.0mnplus;0.8 days after the operation, the catheter was removed after a week, and the double J tube was removed at 1 month. Follow-up intravenous pyelography at 3 months after the operation reveal ureteral stricture in none of the cases. Comparison of the surgical data showed that the time used in each surgical process was significantly shorter in the 3D group than in the 2D group (P<0.05). 3D laparoscopic surgery allowed more precise operation by providing a good sense of depth as in an open surgery to reduce the operation time. CONCLUSIONS: As a minimally invasive surgical technique, 3D laparoscopic surgery facilitates more precise and easier operation compared with 2D laparoscopy in ureter lithotomy. PMID- 26806758 TI - A new ratiometric fluorescent probe for rapid, sensitive and selective detection of endogenous hydrogen sulfide in mitochondria. AB - We have developed a new ratiometric fluorescent probe composed of a coumarin merocyanine dyad based on the FRET mechanism. The probe showed clear dual emission signal changes in blue and red spectral windows upon addition of H2S in a dose dependent manner under a single wavelength excitation. The probe targeted mitochondria with high selectivity and sensitivity toward H2S. PMID- 26806759 TI - Hematopoietic stem cell transplantation for inborn errors of metabolism: A report from the Research Committee on Transplantation for Inborn Errors of Metabolism of the Japanese Ministry of Health, Labour and Welfare and the Working Group of the Japan Society for Hematopoietic Cell Transplantation. AB - A total of 216 patients with IEM were treated by allogeneic HSCT in Japan from 1985 until 2010. The results of UCBT have improved, and the OS rate of UCBT (81.9%) was not different from those of RBMT (87.2%) or UBMT (73.9%) in 2000 2010. However, EFS rates in RBMT (73.2%) and UBMT (62.2%) were better than that in UCBT (49.5%), and the difference between RBMT and UCBT was significant (p = 0.01). The EFS rate of patients conditioned by RIC (74.6%) was comparable or slightly better than in those who underwent MAC with irradiation (57.9%) or without irradiation (54.2%) in 2000-2010. A more pronounced trend was observed toward differential EFS for UCBT in 2000-2010: RIC (62.9%), MAC with irradiation (20.0%), and MAC without irradiation (42.1%). The difference between RIC and MAC with irradiation was significant (p < 0.03). In summary, we report a Japanese registry analysis of HSCT for IEM with improving survival in UCBT. The introduction of RIC after 2000 was considered to contribute to this improvement. UCBT could be recommended for those who lack an HLA-identical sibling donor. PMID- 26806760 TI - The M2 macrophages induce autophagic vascular disorder and promote mouse sensitivity to urethane-related lung carcinogenesis. AB - Tumor vessels are known to be abnormal, with typically aberrant, leaky and disordered vessels. Here, we investigated whether polarized macrophage phenotypes are involved in tumor abnormal angiogenesis and what is its mechanism. We found that there was no difference in chemotaxis of polarized M1 and M2 macrophages to lewis lung carcinoma (LLC) cells and that either M1 or M2 macrophage-conditioned media had no effect on LLC cell proliferation. Unexpectedly, the M2 but not M1 macrophage-conditioned media promoted the proliferation of human umbilical vein endothelial cells (HUVECs) and simultaneously increased endothelial cell permeability in vitro and angiogenic index in the chick embryo chorioallantoic membrane (CAM). The treatment with M2 but not M1 macrophage-conditioned media increased autophagosomes as well as microtubule-associated protein light chain 3B (LC3-B) expression (a robust marker of autophagosomes) but decreased p62 protein expression (a selective autophagy substrate) in HUVECs, the treatment with chloroquine that blocked autophagy abrogated the abnormal angiogenic efficacy of M2 macrophage-conditioned media. These results were confirmed in urethane-induced lung carcinogenic progression. Urethane-induced lung carcinogenesis led to more M2 macrophage phenotype and increased abnormal angiogenesis concomitant with the upregulation of LC3-B and the downregulation of p62. Clodronate liposome-induced macrophage depletion, chloroquine-induced autophagic prevention or salvianolic acid B-induced vascular protection decreased abnormal angiogenesis and lung carcinogenesis. In addition, we found that the tendency of age-related M2 macrophage polarization also promoted vascular permeability and carcinogenesis in urethane carcinogenic progression. These findings indicate that the M2 macrophages induce autophagic vascular disorder to promote lung cancer progression, and the autophagy improvement represents an efficacious strategy for abnormal angiogenesis and cancer prevention. PMID- 26806762 TI - Stability of a double twisted structure in spherical cholesteric droplets. AB - We found for the first time the stabilization of a double twisted structure in cholesteric liquid crystals confined to small spherical droplets under weak anchoring conditions. The direct observation of the droplets using a polarized microscope revealed the physical properties of the structure. The experimental results showed that the stability of the double twisted structure is determined by the relationship between the helical pitch length and the droplet size. We theoretically analyzed the structural stability by the calculation of the Frank elastic free energy including the surface elastic term, and succeeded in explaining the experimental results. In this paper, we concluded that the stability of the double twisted structure is determined by the competition between the surface and the bulk elasticity. PMID- 26806761 TI - Clinical characteristics of chronic lymphocytic leukemia occurring in chornobyl cleanup workers. AB - The recently demonstrated radiation-induction of chronic lymphocytic leukemia (CLL) raises the question as to whether the amount of radiation exposure influences any of the clinical characteristics of the disease. We evaluated the relationship between bone marrow radiation doses and clinical characteristics and survival of 79 CLL cases diagnosed during 1986-2006 in a cohort of 110 645 male workers who participated in the cleanup work of the Chornobyl nuclear accident in Ukraine in 1986. All diagnoses were confirmed by an independent International Hematology Panel. Patients were followed up to the date of death or end of follow up on 31 October 2010. The median age at diagnosis was 57 years. Median bone marrow dose was 22.6 milligray (mGy) and was not associated with time between exposure and clinical diagnosis of CLL (latent period), age, peripheral blood lymphocyte count or clinical stage of disease in univariate and multivariate analyses. Latent period was significantly shorter among those older at first exposure, smokers and those with higher frequency of visits to the doctor prior to diagnosis. A significant increase in the risk of death with increasing radiation dose was observed (p = 0.03, hazard ratio = 2.38, 95% confidence interval: 1.11,5.08 comparing those with doses >=22 mGy to doses <22 mGy). After adjustment for radiation dose, survival of CLL cases was significantly shorter among those with younger age at first exposure, higher peripheral blood lymphocyte count, more advanced clinical stage of disease and older age at diagnosis (all p < 0.05). This is the first study to examine association between bone marrow radiation doses from the Chornobyl accident and clinical manifestations of the CLL in Chornobyl cleanup workers. The current study provides new evidence on the association of radiation dose and younger age at first radiation exposure at Chornobyl with shorter survival after diagnosis. Future studies are necessary with more cases in order to improve the statistical power of these analyses and to determine their significance. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26806764 TI - First instar larvae morphology of Opiinae (Hymenoptera: Braconidae) parasitoids of Anastrepha (Diptera: Tephritidae) fruit flies. Implications for interspecific competition. AB - The morphology of the first instars of the Opiinae braconids Diachasmimorpha longicaudata, Doryctobracon areolatus, Doryctobracon crawfordi, Utetes anastrephae and Opius hirtus (the first is exotic, and the others are natives to Mexico), parasitoids of Anastrepha fruit flies, are described and compared. The possible implications on interspecific competition among these species are discussed. The most significant adaptations found were: (1) the mouth apparatus, where the large mandibles and fang-shaped maxillary lobes present in D. longicaudata and U. anastrephae larvae were absent in O. hirtus, D. areolatus and D. crawfordi larvae, and (2) the degree of mobility for exploration and escape, such as the lateral and caudal appendages that were only present in D. longicaudata (ventrolateral appendages in the base of the head capsule), U. anastrephae (caudal lobe with two appendages) and D. areolatus (caudal lobe with a round apex with a globular shape). The first instar larvae of the species D. longicaudata show morphological adaptations that apparently confer competitive advantages against the larvae of D. areolatus, D. crawfordi and O. hirtus. However, the first instar larvae of U. anastrephae show larger mandibles, an adaptation that could enable this species to resist competition from D. longicaudata. PMID- 26806763 TI - Water-Borne Endovascular Embolics Inspired by the Undersea Adhesive of Marine Sandcastle Worms. AB - Transcatheter embolization is used to treat vascular malformations and defects, to control bleeding, and to selectively block blood supply to tissues. Liquid embolics are used for small vessel embolization that require distal penetration. Current liquid embolic agents have serious drawbacks, mostly centered around poor handling characteristics and toxicity. In this work, a water-borne in situ setting liquid embolic agent is described that is based on electrostatically condensed, oppositely charged polyelectrolytes-complex coacervates. At high ionic strengths, the embolic coacervates are injectable fluids that can be delivered through long narrow microcatheters. At physiological ionic strength, the embolic coacervates transition into a nonflowing solid morphology. Transcatheter embolization of rabbit renal arteries demonstrated capillary level penetration, homogeneous occlusion, and 100% devascularization of the kidney, without the embolic crossing into venous circulation. The benign water-borne composition and setting mechanism avoids many of the problems of current liquid embolics, and provides precise temporal and spatial control during endovascular embolization. PMID- 26806767 TI - [Work-related stress: Implications for physical and mental health]. PMID- 26806768 TI - Neuroscience of resilience and vulnerability for addiction medicine: From genes to behavior. AB - Addiction is a complex behavioral disorder arising from roughly equal contributions of genetic and environmental factors. Behavioral traits such as novelty-seeking, impulsivity, and cue-reactivity have been associated with vulnerability to addiction. These traits, at least in part, arise from individual variation in functional neural systems, such as increased striatal dopaminergic activity and decreased prefrontal cortical control over subcortical emotional and motivational responses. With a few exceptions, genetic studies have largely failed to consistently identify specific alleles that affect addiction liability. This may be due to the multifactorial nature of addiction, with different genes becoming more significant in certain environments or in certain subsets of the population. Epigenetic mechanisms may also be an important source of risk. Adolescence is a particularly critical time period in the development of addiction, and environmental factors at this stage of life can have a large influence on whether inherited risk factors are actually translated into addictive behaviors. Knowledge of how individual differences affect addiction liability at the level of genes, neural systems, behavioral traits, and sociodevelopmental trajectories can help to inform and improve clinical practice. PMID- 26806765 TI - Unusual presentations in patients with E200K familial Creutzfeldt-Jakob disease. AB - BACKGROUND AND PROPOSE: Familial Creutzfeldt-Jakob disease (fCJD) in Jews of Libyan ancestry is caused by an E200K mutation in the PRNP gene. The typical presenting symptoms include cognitive decline, behavioral changes and gait disturbances; however, some patients may have an unusual presentation such as a stroke-like presentation, alien hand syndrome or visual disturbances. The aim of this paper is to describe uncommon presentations in our series of consecutive patients with E200K fCJD. METHODS: The study group included consecutive fCJD patients followed up as part of a longitudinal prospective study ongoing since 2003 or hospitalized since 2005. The clinical diagnosis of probable CJD was based on accepted diagnostic criteria and supported by typical magnetic resonance imaging, electroencephalographic findings, elevated cerebrospinal fluid tau protein levels and by genetic testing for the E200K mutation. Disease symptoms and signs were retrieved from the medical files. RESULTS: The study population included 77 patients (42 men) with a mean age of disease onset of 60.6 +/- 7.2 years. The most prevalent presenting symptoms were cognitive decline followed by gait impairment and behavioral changes. However, six patients had an unusual presentation including auditory agnosia, monoparesis, stroke-like presentation, facial nerve palsy, pseudobulbar syndrome and alien hand syndrome. CONCLUSIONS: Our case series illustrates the wide phenotypic variability of the clinical presentation of patients with fCJD and widens the clinical spectrum of the disease. A high level of clinical suspicion may prove useful in obtaining early diagnosis and therefore avoiding costly and inefficient diagnostic and therapeutic strategies. PMID- 26806769 TI - Drug-induced neurotoxicity in addiction medicine: From prevention to harm reduction. AB - Neurotoxicity is considered as a major cause of neurodegenerative disorders. Most drugs of abuse have nonnegligible neurotoxic effects many of which are primarily mediated by several dopaminergic and glutamatergic neurotransmitter systems. Although many researchers have investigated the medical and cognitive consequences of drug abuse, the neurotoxicity induced by these drugs still requires comprehensive attention. The science of neurotoxicity promises to improve preventive and therapeutic strategies for brain disorders such as Alzheimer disease and Parkinson's disease. However, its clinical applications for addiction medicine remain to be defined adequately. This chapter reviews the most commonly discussed mechanisms underlying neurotoxicity induced by common drugs of abuse including amphetamines, cocaine, opiates, and alcohol. In addition, the known factors that trigger and/or predispose to drug-induced neurotoxicity are discussed. These factors include drug-related, individual-related, and environmental insults. Moreover, we introduce some of the potential pharmacological antineurotoxic interventions deduced from experimental animal studies. These interventions involve various targets such as dopaminergic system, mitochondria, cell death signaling, and NMDA receptors, among others. We conclude the chapter with a discussion of addicted patients who might benefit from such interventions. PMID- 26806770 TI - Stress psychobiology in the context of addiction medicine: from drugs of abuse to behavioral addictions. AB - In this chapter, we briefly review the basic biology of psychological stress and the stress response. We propose that psychological stress and the neurobiology of the stress response play in substance use initiation, maintenance, and relapse. The proposed mechanisms for this include, on the one hand, the complex interactions between biological mediators of the stress response and the dopaminergic reward system and, on the other hand, mediators of the stress response and other systems crucial in moderating key addiction-related behaviors such as endogenous opioids, the sympathetic-adrenal-medullary system, and endocannabinoids. Exciting new avenues of study including genomics, sex as a moderator of the stress response, and behavioral addictions (gambling, hypersexuality, dysfunctional internet use, and food as an addictive substance) are also briefly presented within the context of stress as a moderator of the addictive process. PMID- 26806771 TI - Reinforcement principles for addiction medicine; from recreational drug use to psychiatric disorder. AB - The transition from recreational drug use to addiction can be conceptualized as a pathological timeline whereby the psychological mechanisms responsible for disordered drug use evolve from positive reinforcement to favor elements of negative reinforcement. Abused substances (ranging from alcohol to psychostimulants) are initially ingested at regular occasions according to their positive reinforcing properties. Importantly, repeated exposure to rewarding substances sets off a chain of secondary reinforcing events, whereby cues and contexts associated with drug use may themselves become reinforcing and thereby contribute to the continued use and possible abuse of the substance(s) of choice. Indeed, the powerful reinforcing efficacy of certain drugs may eclipse that of competing social rewards (such as career and family) and lead to an aberrant narrowing of behavioral repertoire. In certain vulnerable individuals, escalation of drug use over time is thought to drive specific molecular neuroadaptations that foster the development of addiction. Research has identified neurobiological elements of altered reinforcement following excessive drug use that comprise within-circuit and between-circuit neuroadaptations, both of which contribute to addiction. Central to this process is the eventual potentiation of negative reinforcement mechanisms that may represent the final definitive criterion locking vulnerable individuals into a persistent state of addiction. Targeting the neural substrates of reinforcement likely represents our best chances for therapeutic intervention for this devastating disease. PMID- 26806772 TI - Neuroscience of attentional processes for addiction medicine: from brain mechanisms to practical considerations. AB - The present chapter first argues how having a goal for procuring alcohol or other substances leads to the development of a time-binding, dynamic, and goal oriented motivational state termed current concern, as the origin of substance-related attentional bias. Next, it discusses the importance of attentional bias in the development, continuation of, and relapsing to substance abuse. It further proceeds with a review of selective evidence from cognitive psychology that helps account for making decisions about using an addictive substance or refraining from using it. A discussion on the various brain loci that are involved in attentional bias and other kinds of cue reactivity is followed by presenting findings from neurocognitive research. Finally, from an interdisciplinary perspective, the chapter presents new trends and ideas that can be applied to addiction-related cognitive measurement and training. PMID- 26806773 TI - Neuroscience of learning and memory for addiction medicine: from habit formation to memory reconsolidation. AB - Identifying effective pharmacological treatments for addictive disorders has remained an elusive goal. Many different classes of drugs have shown some efficacy in preclinical models, but the number of effective clinical therapeutics has remained stubbornly low. The persistence of drug use and the high frequency of relapse is at least partly attributable to the enduring ability of environmental stimuli associated with drug use to maintain behavioral patterns of drug use and induce craving during abstinence. We propose that stimuli associated with drug use exert such powerful control over behavior through the development of abnormally strong memories, and their ability to initiate subconscious sequences of motor actions (habits) that promote uncontrolled drug use. In this chapter, we will review the evidence suggesting that drugs of abuse strengthen associations with cues in the environment and facilitate habit formation. We will also discuss potential mechanisms for disrupting memories associated with drug use to help improve treatments for addiction. PMID- 26806774 TI - Neuroscience of drug craving for addiction medicine: From circuits to therapies. AB - Drug craving is a dynamic neurocognitive emotional-motivational response to a wide range of cues, from internal to external environments and from drug-related to stressful or affective events. The subjective feeling of craving, as an appetitive or compulsive state, could be considered a part of this multidimensional process, with modules in different levels of consciousness and embodiment. The neural correspondence of this dynamic and complex phenomenon may be productively investigated in relation to regional, small-scale networks, large scale networks, and brain states. Within cognitive neuroscience, this approach has provided a long list of neural and cognitive targets for craving modulations with different cognitive, electrical, or pharmacological interventions. There are new opportunities to integrate different approaches for carving management from environmental, behavioral, psychosocial, cognitive, and neural perspectives. By using cognitive neuroscience models that treat drug craving as a dynamic and multidimensional process, these approaches may yield more effective interventions for addiction medicine. PMID- 26806775 TI - Response inhibition and addiction medicine: from use to abstinence. AB - Historically, neuroscientific research into addiction has emphasized affective and reinforcement mechanisms as the essential elements underlying the pursuit of drugs, their abuse, and difficulties associated with abstinence. However, research over the last decade or so has shown that cognitive control systems, associated largely but not exclusively with the frontal lobes, are also important contributors to drug use behaviors. Here, we focus on inhibitory control and its contribution to both current use and abstinence. A body of evidence points to impaired inhibitory abilities across a range of drugs of abuse. Typically, studies suggest that substance-abusing individuals are characterized by relative hypoactivity in brain systems underlying inhibitory control. In contrast, abstinent users tend to show either normal or supernormal levels of activity in the same systems attesting to the importance of inhibitory control in suppressing the drug use urges that plague attempts at abstinence. In this chapter, the brain and behavioral basis of response inhibition will be reviewed, with a focus on neuroimaging studies of response inhibition in current and abstinent drug abusers. PMID- 26806777 TI - Neuroscience of nicotine for addiction medicine: novel targets for smoking cessation medications. AB - Morbidity and mortality associated with tobacco smoking constitutes a significant burden on healthcare budgets all over the world. Therefore, promoting smoking cessation is an important goal of health professionals and policy makers throughout the world. Nicotine is a major psychoactive component in tobacco that is largely responsible for the widespread addiction to tobacco. A majority of the currently available FDA-approved smoking cessation medications act via neuronal nicotinic receptors. These medications are effective in approximately half of all the smokers, who want to quit and relapse among abstinent smokers continues to be high. In addition to relapse among abstinent smokers, unpleasant effects associated with nicotine withdrawal are a major motivational factor in continued tobacco smoking. Over the last two decades, animal studies have helped in identifying several neural substrates that are involved in nicotine-dependent behaviors including those associated with nicotine withdrawal and relapse to tobacco smoking. In this review, first the role of specific brain regions/circuits that are involved in nicotine dependence will be discussed. Next, the review will describe the role of specific nicotinic receptor subunits in nicotine dependence. Finally, the review will discuss the role of classical neurotransmitters (dopamine, serotonin, noradrenaline, glutamate, and gamma aminobutyric acid) as well as endogenous opioid and endocannabinoid signaling in nicotine dependence. The nicotinic and nonnicotinic neural substrates involved in nicotine-dependent behaviors can serve as possible targets for future smoking cessation medications. PMID- 26806776 TI - Neuroscience of inhibition for addiction medicine: from prediction of initiation to prediction of relapse. AB - A core deficit in drug addiction is the inability to inhibit maladaptive drug seeking behavior. Consistent with this deficit, drug-addicted individuals show reliable cross-sectional differences from healthy nonaddicted controls during tasks of response inhibition accompanied by brain activation abnormalities as revealed by functional neuroimaging. However, it is less clear whether inhibition related deficits predate the transition to problematic use, and, in turn, whether these deficits predict the transition out of problematic substance use. Here, we review longitudinal studies of response inhibition in children/adolescents with little substance experience and longitudinal studies of already addicted individuals attempting to sustain abstinence. Results show that response inhibition and its underlying neural correlates predict both substance use outcomes (onset and abstinence). Neurally, key roles were observed for multiple regions of the frontal cortex (e.g., inferior frontal gyrus, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex). In general, less activation of these regions during response inhibition predicted not only the onset of substance use, but interestingly also better abstinence-related outcomes among individuals already addicted. The role of subcortical areas, although potentially important, is less clear because of inconsistent results and because these regions are less classically reported in studies of healthy response inhibition. Overall, this review indicates that response inhibition is not simply a manifestation of current drug addiction, but rather a core neurocognitive dimension that predicts key substance use outcomes. Early intervention in inhibitory deficits could have high clinical and public health relevance. PMID- 26806778 TI - Neuroscience of alcohol for addiction medicine: Neurobiological targets for prevention and intervention in adolescents. AB - Structural and functional neuroimaging studies indicate that heavy alcohol use during adolescence may be neurotoxic to the brain. This chapter reviews the neuroimaging findings in cross-sectional and longitudinal studies of adolescent heavy alcohol users. These youth exhibit reductions in prefrontal, hippocampal, and cerebellar brain volume, decreased frontoparietal, and increased frontolimbic white matter integrity, as well as alterations in blood oxygen level-dependent response during working memory, inhibitory control, verbal encoding, decision making, and reward processing-some of which appear to differ between males and females. Although some exist, additional longitudinal studies will significantly advance addiction medicine by aiding prevention scientists and treatment providers to develop neurobiologically informed ways of strengthening neural networks prior to and after the onset of heavy alcohol use, thereby promoting healthy cognitive functioning across the adolescent period. PMID- 26806779 TI - Neuroscience of opiates for addiction medicine: From stress-responsive systems to behavior. AB - Opiate addiction, similarly to addiction to other psychoactive drugs, is chronic relapsing brain disease caused by drug-induced short-term and long-term neuroadaptations at the molecular, cellular, and behavioral levels. Preclinical research in laboratory animals has found important interactions between opiate exposure and stress-responsive systems. In this review, we will discuss the dysregulation of several stress-responsive systems in opiate addiction: vasopressin and its receptor system, endogenous opioid systems (including proopiomelanocortin/mu opioid receptor and dynorphin/kappa opioid receptor), orexin and its receptor system, and the hypothalamic-pituitary-adrenal axis. A more complete understanding of how opiates alter these stress systems, through further laboratory-based studies, is required to identify novel and effective pharmacological targets for the long-term treatment of heroin addiction. PMID- 26806780 TI - Opioid neuroscience for addiction medicine: From animal models to FDA approval for alcohol addiction. AB - Alcohol addiction is one of the most common and devastating diseases in the world. Given the tremendous heterogeneity of alcohol-addicted individuals, it is unlikely that one medication will help nearly all patients. Thus, there is a clear need to develop predictors of response to existing medications. Naltrexone is a mu opioid receptor antagonist which has been approved in the United States for treatment of alcohol addiction since 1994. It has limited efficacy, in part due to noncompliance, but many patients do not respond despite high levels of compliance. There are reports that a mis-sense single-nucleotide polymorphism (rs179919 or A118G) in the mu opioid receptor gene predicts a favorable response to naltrexone if an individual carries a "G" allele. This chapter will review the evidence for this hypothesis. The data suggest that the "G" allele has a complex role in alcohol addiction, increasing the rewarding valence of alcohol. Whether the G allele increases risk for alcoholism and whether it predisposes to a beneficial naltrexone response among alcohol-addicted persons must await additional research with large sample sizes of multiple ethnicities in prospective clinical trials. PMID- 26806782 TI - Clinical neuroscience of amphetamine-type stimulants: From basic science to treatment development. AB - Abuse of amphetamine-type stimulants (ATS) poses a significant public health concern with known neurotoxic and neurocognitive effects to the user. In this chapter, we seek to integrate the latest research on ATS, particularly methamphetamine, by covering areas of pharmacology, neurocognitive effects, and the treatment of ATS use disorders with the goal of advancing the clinical neuroscience of ATS and highlighting avenues for future research. PMID- 26806783 TI - Behavioral addictions in addiction medicine: from mechanisms to practical considerations. AB - Recent progress has been made in our understanding of nonsubstance or "behavioral" addictions, although these conditions and their most appropriate classification remain debated and the knowledge basis for understanding the pathophysiology of and treatments for these conditions includes important gaps. Recent developments include the classification of gambling disorder as a "Substance-Related and Addictive Disorder" in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and proposed diagnostic criteria for Internet Gaming Disorder in Section 3 of DSM-5. This chapter reviews current neuroscientific understandings of behavioral addictions and the potential of neurobiological data to assist in the development of improved policy, prevention, and treatment efforts. PMID- 26806781 TI - Competing neurobehavioral decision systems theory of cocaine addiction: From mechanisms to therapeutic opportunities. AB - Cocaine dependence is a difficult-to-treat, chronically relapsing disorder. Multiple scientific disciplines provide distinct perspectives on this disorder; however, connections between disciplines are rare. The competing neurobehavioral decision systems (CNDS) theory posits that choice results from the interaction between two decision systems (impulsive and executive) and that regulatory imbalance between systems can induce pathology, including addiction. Using this view, we integrate a diverse set of observations on cocaine dependence, including bias for immediacy, neural activity and structure, developmental time course, behavioral comorbidities, and the relationship between cocaine dependence and socioeconomic status. From the CNDS perspective, we discuss established and emerging behavioral, pharmacological, and neurological treatments and identify possible targets for future treatments. The ability of the CNDS theory to integrate diverse findings highlights its utility for understanding cocaine dependence and supports that dysregulation between the decision systems contributes to addiction. PMID- 26806784 TI - Neural systems implicated in obesity as an addictive disorder: from biological to behavioral mechanisms. AB - Contributing factors to obesity have been identified, yet prevention and treatment efforts have had limited long-term success. It has recently been suggested that some individuals may experience an addictive-like response to certain foods, such as losing control over consumption and continued consumption despite negative consequences. In support, shared biological and behavioral features seem to exist between "food addiction" and traditional substance-use disorders. "Food addiction" may be another important contributor to obesity. The current chapter reviews existing literature regarding neural systems implicated similarly in obesity and addiction, discusses unique considerations for addictive like eating, and proposes directions for future research regarding "food addiction" as an emerging construct for addiction medicine. PMID- 26806785 TI - Preface: Neuroscience for Addiction Medicine: From Prevention to Rehabilitation. PMID- 26806786 TI - Physiological Levels of Pentraxin 3 and Albumin Attenuate Vascular Endothelial Cell Damage Induced by Histone H3 In Vitro. AB - OBJECTIVE: Extracellular histones have strong toxicity against the vascular ECs, however, the damage is significantly attenuated in the serum. Although several plasma proteins such as albumin, APC, and PTX3 are known to inhibit the actions of histones, it is still unclear as to which plasma proteins play predominant role. The purpose of this study was to search for the major inhibitors in the serum. METHODS: ECs were cultured in serum-free medium and histone H3 was added. The effects of albumin, low-, medium-, and high-concentration of APC and PTX3 were examined by time-lapse morphological observation and by immunofluorescent staining. The treatment effects were also assessed by the cell viability assay. RESULTS: Both 5% and 2.5% albumin, medium- and high-concentration APC, and medium and high-concentration PTX3 exerted significant protective effect. In case of damage induced by high-concentration histone H3, all of albumin, APC and PTX3 exerted effects in a concentration-dependent manner. Above results were also confirmed by the cell viability assay. CONCLUSION: Because albumin and PTX3 inhibited histone-induced damage at physiological levels found in serum, these proteins are expected to be major histone inhibitors in vivo. PMID- 26806787 TI - Treatment of potato farm wastewater with sand filtration. AB - This study examined sand filtration as a component of a potato farm wastewater treatment system. Two different sand filter designs, saturated flow and unsaturated flow, were evaluated at three different loading rates: 34, 68, and 136 L m(-2) d(-1). Filter design had a significant effect, with unsaturated flow sand filters having significantly (p < .05) better total suspended solids (TSS) removal (89%) than saturated flow sand filters did (79%). Loading rate also had a significant (p < .05) effect, given that the lowest loading rate had higher mass removal for TSS than the higher loading rates did. Overall, all sand filters removed TSS, 5-d biochemical oxygen demand, and total phosphorus well (62-99%). Total nitrogen removal was twice as high in unsaturated flow filters (53%) than in saturated flow filters (27%), because of the recurring cycle of aerobic and anaerobic conditions during sand saturation and drying in unsaturated flow sand filters. PMID- 26806788 TI - Evidence against ZNF469 being causative for keratoconus in Polish patients. AB - PURPOSE: Keratoconus (KTCN) is a degenerative disorder characterized by stromal thinning and protrusion of the cornea, resulting in severe impairment of visual function. A recent study proposed that rare heterozygous mutations in ZNF469 determine KTCN aetiology. METHODS: To investigate the contribution of ZNF469 to KTCN, we Sanger sequenced ZNF469 in 42 unrelated Polish patients with KTCN and 49 Polish individuals with high myopia (HM) and compared the results with whole exome sequencing (WES) data performed in 268 Polish individuals without ocular abnormalities. RESULTS: The average number of ZNF469 non-synonymous variants was 16.31 and 16.0 for individuals with KTCN and HM, respectively (p = 0.3724). All identified variants were previously reported. Alternative allele frequency (AAF) was determined based on the WES results. Among missense variants, only one (rs528085780) has AAF <= 0.001 and was identified in one patient with sporadic KTCN. However, the resulting Arg1864Lys substitution was not predicted to be deleterious. CONCLUSION: In summary, we have not found a significant enrichment of sequence variants in ZNF469 in Polish patients with KTCN. High prevalence of ZNF469 variants identified in our KTCN group is typical for a common genetic variation observed in general population. Our findings indicate that variation in ZNF469 is not responsible for KTCN and other genetic variants are involved in the development and progression of this disease in Polish patients. PMID- 26806789 TI - Self-sufficing H2O2-responsive nanocarriers through tumor-specific H2O2 production for synergistic oxidation-chemotherapy. AB - One of distinct features in tumor tissues is the elevated concentration of reactive oxygen species (ROS) during tumor immortality, proliferation and metastasis. However, ROS-responsive materials are rarely utilized in the field of in vivo tumoral ROS-responsive applications due to the fact that the intrinsic ROS level in the tumors could not escalate to an adequate level that the developed materials can possibly respond. Herein, palmitoyl ascorbate (PA) as a prooxidant for hydrogen peroxide (H2O2) production in tumor tissue is strategically compiled into a H2O2-responsive camptothecin (CPT) polymer prodrug micelle, which endowed the nanocarriers with self-sufficing H2O2 stimuli in tumor tissues. Molecular oncology manifests the hallmarks of tumoral physiology with deteriorating propensity in eliminating hazardous ROS. H2O2 production was demonstrated to specifically sustain in tumors, which not only induced tumor cell apoptosis by elevated oxidation stress but also served as autochthonous H2O2 resource to trigger CPT release for chemotherapy. Excess H2O2 and released CPT could penetrate into cells efficiently, which showed synergistic cytotoxicity toward cancer cells. Systemic therapeutic trial revealed potent tumor suppression of the proposed formulation via synergistic oxidation-chemotherapy. This report represents a novel nanomedicine platform combining up-regulation of tumoral H2O2 level and self-sufficing H2O2-responsive drug release to achieve novel synergistic oxidation-chemotherapy. PMID- 26806790 TI - Rolapitant: a pooled analysis of its efficacy and safety in the prophylaxis of chemotherapy-induced nausea and vomiting. AB - BACKGROUND: We conducted a pooled analysis of rolapitant-containing regimens versus control in the prophylaxis of chemotherapy-induced nausea and vomiting. METHODOLOGY: Eligible studies included randomized studies evaluating rolapitant containing regimens in the settings of highly emetogenic and moderately emetogenic chemotherapy. RESULTS: The pooled relative risk for complete response in the overall phase was 1.23 (95% CI: 1.18-1.33; p < 0.00001), the pooled relative risk for no significant nausea in the overall phase was 1.17 (95% CI: 1.04-1.32; p = 0.008) and the pooled RR for no emesis in the overall phase was 1.24 (95% CI: 1.18-1.31; p < 0.00001). CONCLUSION: Rolapitant-based regimens are associated with higher rates of complete response, no significant nausea and no emesis with highly/moderately emetogenic chemotherapy compared with control regimens. PMID- 26806791 TI - Mechanical behavior comparison of spider and silkworm silks using molecular dynamics at atomic scale. AB - Spider and silkworm silk proteins have received much attention owing to their inherent structural stability, biodegradability, and biocompatibility. These silk protein materials have various mechanical characteristics such as elastic modulus, ultimate strength and fracture toughness. While the considerable mechanical characteristics of the core crystalline regions of spider silk proteins at the atomistic scale have been investigated through several experimental techniques and computational studies, there is a lack of comparison between spider and silkworm fibroins in the atomistic scale. In this study, we investigated the differences between the mechanical characteristics of spider and silkworm fibroin structures by applying molecular dynamics and steered molecular dynamics. We found that serine amino acids in silkworm fibroins not only increased the number of hydrogen bonds, but also altered their structural characteristics and mechanical properties. PMID- 26806792 TI - Diastolic Hypotension in a Tertiary Care Hypertension Clinic: Have We Gone Too Far? AB - BACKGROUND: Treatment-induced diastolic hypotension has been associated with an increased risk of adverse cardiovascular events in post hoc analyses of major blood pressure (BP)-lowering trials. We undertook this retrospective study to assess the prevalence and risk factors for diastolic hypotension among patients referred to a tertiary care hypertension clinic. METHODS: Charts of all active patients were reviewed, and BP at the initial visit was compared with BP at the first visit at which the systolic BP target was achieved or the last visit if the target was not achieved. Diastolic hypotension was defined as diastolic BP < 60 mm Hg. RESULTS: Four hundred sixty-six patients were identified. The mean baseline BP was 142/77 mm Hg, and the mean number of medications was 2.9. Forty nine (10.5%) patients had diastolic hypotension at baseline, and a further 68 (16%) acquired it during follow-up. Those with baseline diastolic hypotension had no change in the number of antihypertensive medications being taken on follow-up (mean, 3.6-3.7; P = 0.46), and diastolic BP did not change (53-55 mm Hg; P = 0.07). On adjusted analysis, older age (odds ratio [OR], 1.04; P = 0.0008), diabetes (OR, 2.8; P = 0.002), higher baseline systolic BP (OR, 1.03; P < 0.001), and lower baseline diastolic BP (OR, 0.003; P < 0.001) were predictors of diastolic hypotension at follow-up. CONCLUSIONS: Treating systolic hypertension resulted in diastolic hypotension in 27% of patients followed at a tertiary care hypertension clinic. Its presence does not usually result in the reduction of antihypertensive therapy. Older patients, patients with diabetes, and patients with isolated systolic hypertension appear to be more susceptible to the development of diastolic hypotension during therapy. PMID- 26806793 TI - Association between Carotid Intima-Media Thickness and Cognitive Impairment in a Chinese Stroke Population: A Cross-sectional Study. AB - This study aimed to investigate the potential associations between carotid intima media thickness and cognitive impairment among patients with acute ischemic stroke and to identify the clinical implications. We measured carotid intima media thickness (IMT) and performed the Mini-Mental State Examination (MMSE) upon the admission of 1,826 acute ischemic stroke patients. The association between IMT and cognitive impairment evaluated by the MMSE was assessed with a multivariate regression analysis. Other clinical variables of interest were also assessed. After adjusting for potential confounders, participants in the highest IMT quartile had a higher likelihood of having cognitive impairments compared with the lowest IMT quartile (odds ratio: 3.01, 95% confidence interval: 2.07 4.37, p < 0.001). Stratified analyses indicated that this positive correlation was similar for the maxIMT and meanIMT of carotid artery measurements. A positive correlation was found between IMT and cognitive impairment in participants with acute ischemic stroke. PMID- 26806794 TI - Detecting Polygenic Evolution: Problems, Pitfalls, and Promises. AB - Unraveling the genetic basis of organismal form and function remains one of the major goals of evolutionary biology. Theory has long supported a model of polygenic evolution in which quantitative traits are underpinned by many genes of small effect, but empirical methods have lacked the power to detect causative loci when effect sizes are small or moderate. We (i) review traditional approaches used for identifying the molecular basis of phenotypic traits, to highlight the inherent problems and pitfalls that bias them towards the detection of large-effect loci. We then (ii) outline the promises of recent statistical frameworks to detect polygenic signatures of trait evolution, and discuss some of the first studies in evolutionary biology employing these approaches. Lastly, we (iii) outline future directions and point to areas that still need development. PMID- 26806796 TI - P19 contributes to Mycoplasma mycoides subsp. mycoides adhesion to EBL cells. AB - Mycoplasma mycoides subsp. mycoides (Mmm) is the causative agent of contagious bovine pleuropneumonia (CBPP). The virulent Mmm Ben-1 strain was isolated from the lung of a CBPP-infected cow in China in the 1950s. To attenuate the virulence of the Ben-1 strain and preserve its protective ability, the isolate was re isolated after inoculation into the testicles of rabbits and into the rabbit thorax. As a result, after the subsequent isolates were continuously passaged 468 times in rabbits, its pathogenicity to cattle decreased. However, the molecular mechanisms leading to attenuation of the Mmm Ben-1 remain unknown. We compared the entire genomes of the Ben-1 strain and the 468 th generation strain passaged in rabbits (Ben-468) and discovered that a putative protein gene named p19 was absent from the Ben-468 strain. The p19 gene was cloned and expressed in Escherichia coli to obtain recombinant P19 (rP19). Western blot analysis demonstrated that the P19 protein is detected in the cell-membrane fraction, the cell-soluble cytosolic fraction and whole-cell lysate of the Mmm Ben-1 strain. The rP19 can interact with international standard serum against CBPP. Immunostaining visualised via confocal laser scanning microscopy indicated that P19 is able to adhere to embryonic bovine lung (EBL) cells, and this finding was also confirmed by a sandwich ELISA. We also found that anti-rP19 serum could inhibit the adhesion of the Mmm Ben-1 total proteins to EBL cells. PMID- 26806799 TI - Vascular reactivity of rabbit isolated renal and femoral resistance arteries in renal wrap hypertension. AB - In rabbits with cellophane renal wrap hypertension, hindquarter and total vascular resistance changes to pressor and depressor agents are amplified compared to those of normotensive rabbits. The aim of the present study was to evaluate the in vitro pharmacodynamics of hypertensive and normotensive rabbit small artery segments isolated from the renal and hindquarter vascular beds. Using wire myography, the full range (Emax) and sensitivity (EC50) to a range of agonists of segments of renal interlobar (~ 600 um i.d.), renal arcuate (~ 250 um i.d.) and deep femoral branch (~ 250 um i.d.) arteries were assessed under normalised conditions of passive tension. Interlobar arteries from hypertensive rabbits were more sensitive (EC50) than those from normotensive rabbits to noradrenaline (6-fold), methoxamine (3-fold) and angiotensin II (3-fold). Arcuate artery reactivity was largely unaffected by hypertension. Deep femoral arteries from hypertensive rabbits had enhanced sensitivity only to noradrenaline (2-fold) and methoxamine (4-fold). Sensitivity to relaxation by acetylcholine was unaffected by hypertension in all arteries. Deep femoral arteries from hypertensive rabbits were more sensitive to sodium nitroprusside than normotensive counterparts. Adenosine caused little relaxation in renal arteries, but full relaxation in deep femoral arteries, unaltered by hypertension. This study found substantial heterogeneity in the pharmacodynamic profile of vessels isolated from different vascular beds and between arterial segments within the kidney. These profiles were differentially affected by hypertension suggesting that hypertension per se is not a resultant of general vascular dysfunction. PMID- 26806798 TI - Catastrophic Intracranial Hemorrhages after IV tPA in a Patient with Insidious Onset of Fever and Back Pain. AB - Infective endocarditis is associated with unstable infective vegetations, which have a propensity to embolize and cause embolic events, such as stroke. Many cases present with an embolic event as the first sign of infective endocarditis. We present a patient who had a history of recent and persistent fever, an acute ischemic stroke treated with intravenous tissue plasminogen activator (IV tPA), and severe, multifocal intracerebral hemorrhage as a complication of tPA treatment. Suspected infective endocarditis in a stroke patient should most likely be considered a contraindication to IV tPA. PMID- 26806805 TI - The impact of health anxiety in patients with relapsing remitting multiple sclerosis: Misperception, misattribution and quality of life. AB - OBJECTIVES: Multiple sclerosis (MS) is a progressive disease with an unpredictable prognosis. Previous studies have reported health anxiety within the MS population. This study examines the effect of health anxiety on MS patients' quality of life (QoL) and evaluates the potential contribution of cognitive factors in maintaining health anxiety. METHODS: A total of 84 patients with relapsing remitting multiple sclerosis (RRMS) were screened for health anxiety. From this sample, a group with relatively high and another group with low anxiety (n = 21 in each group) were identified. A further 21 healthy controls were recruited for comparison. A measure of QoL was then completed. Cognitive biases were investigated by measuring perception and attribution of common bodily symptoms as well as appraisal of performance on neuropsychological and physical fatigue tests. RESULTS: The high health anxiety group reported poorer QoL relative to the other groups, independent of level of disability. They were also more likely to misattribute common bodily changes to MS, and perceive their (objectively intact) performance on tests of cognition and fatigue as being impaired, attributing the cause of impairment to MS. CONCLUSION: Health anxiety may be a factor in mediating the psychosocial impact of MS. Skilled psychological treatment which changes misperception and misattribution may significantly benefit patients with MS and elevated health anxiety. PRACTITIONER POINTS: Clinical implications Health anxiety impacts on quality of life in patients with MS even when disability and other measures of psychological distress are taken into account. High levels of health anxiety distort perceptions of symptoms in patients with MS in line with the predictions made by the cognitive model of health anxiety. Limitations of study This study is limited to patients with RRMS within the relatively early stages of their disease and is based on a small sample size. Health anxiety is correlated with measures of generalized anxiety, depression, and worry, although it is found to have a unique impact on quality of life in patients with MS. PMID- 26806806 TI - Mining the transcriptomes of four commercially important shellfish species for single nucleotide polymorphisms within biomineralization genes. AB - Transcriptional profiling not only provides insights into patterns of gene expression, but also generates sequences that can be mined for molecular markers, which in turn can be used for population genetic studies. As part of a large scale effort to better understand how commercially important European shellfish species may respond to ocean acidification, we therefore mined the transcriptomes of four species (the Pacific oyster Crassostrea gigas, the blue mussel Mytilus edulis, the great scallop Pecten maximus and the blunt gaper Mya truncata) for single nucleotide polymorphisms (SNPs). Illumina data for C. gigas, M. edulis and P. maximus and 454 data for M. truncata were interrogated using GATK and SWAP454 respectively to identify between 8267 and 47,159 high quality SNPs per species (total=121,053 SNPs residing within 34,716 different contigs). We then annotated the transcripts containing SNPs to reveal homology to diverse genes. Finally, as oceanic pH affects the ability of organisms to incorporate calcium carbonate, we honed in on genes implicated in the biomineralization process to identify a total of 1899 SNPs in 157 genes. These provide good candidates for biomarkers with which to study patterns of selection in natural or experimental populations. PMID- 26806807 TI - Toward stratification of patients with pancreatic cancer: Past lessons from traditional approaches and future applications with physical biomarkers. AB - Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate and outcomes have not improved substantially for decades. Significant attention has focused on the biological drivers of the disease, and preclinical work has pointed to multiple biomarker candidates and therapeutic avenues. However, translation of these promising biomarkers and treatment strategies to patients has not been overwhelmingly successful. New strategies to account for the significant heterogeneity of the disease are needed so that rational treatments can be administered. Here, we focus on how physical sciences-based approaches may play a role in stratifying patients for clinical trials, and how this view of PDAC may reinvigorate treatment strategies that have been abandoned after "failing" to fulfill their potential in unselected patient populations. By complementing biological approaches, the development of physical biomarkers of PDAC may help deliver on the promise of personalized medicine for this devastating disease. PMID- 26806808 TI - Development and potential applications of CRISPR-Cas9 genome editing technology in sarcoma. AB - Sarcomas include some of the most aggressive tumors and typically respond poorly to chemotherapy. In recent years, specific gene fusion/mutations and gene over expression/activation have been shown to drive sarcoma pathogenesis and development. These emerging genomic alterations may provide targets for novel therapeutic strategies and have the potential to transform sarcoma patient care. The RNA-guided nuclease CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein-9 nuclease) is a convenient and versatile platform for site-specific genome editing and epigenome targeted modulation. Given that sarcoma is believed to develop as a result of genetic alterations in mesenchymal progenitor/stem cells, CRISPR-Cas9 genome editing technologies hold extensive application potentials in sarcoma models and therapies. We review the development and mechanisms of the CRISPR-Cas9 system in genome editing and introduce its application in sarcoma research and potential therapy in clinic. Additionally, we propose future directions and discuss the challenges faced with these applications, providing concise and enlightening information for readers interested in this area. PMID- 26806809 TI - Granzyme B-based cytolytic fusion protein targeting EpCAM specifically kills triple negative breast cancer cells in vitro and inhibits tumor growth in a subcutaneous mouse tumor model. AB - Triple-negative breast cancer (TNBC) is associated with poor prognosis and high prevalence among young premenopausal women. Unlike in other breast cancer subtypes, no targeted therapy is currently available. Overexpression of epithelial cell adhesion molecule (EpCAM) in 60% of TNBC tumors correlates with poorer prognosis and is associated with cancer stem cell phenotype. Thus, selective elimination of EpCAM(+) TNBC tumor cells is of clinical importance. Therefore, we constructed a fully human targeted cytolytic fusion protein, designated GbR201K-alphaEpCAM(scFv), in which an EpCAM-selective single-chain antibody fragment (scFv) is genetically fused to a granzyme B (Gb) mutant with reduced sensitivity to its natural inhibitor serpin B9. In vitro studies confirmed its specific binding, internalization and cytotoxicity toward a panel of EpCAM-expressing TNBC cells. Biodistribution kinetics and tumor-targeting efficacy using MDA-MB-468 cells in a human TNBC xenograft model in mice revealed selective accumulation of GbR201K-alphaEpCAM(scFv) in the tumors after i.v. injection. Moreover, treatment of tumor-bearing mice demonstrated a prominent inhibition of tumor growth of up to 50 % in this proof-of-concept study. Taken together, our results indicate that GbR201K-alphaEpCAM(scFv) is a promising novel targeted therapeutic for the treatment of TNBC. PMID- 26806810 TI - RETRACTED: MiR-143 inhibits tumor cell proliferation and invasion by targeting STAT3 in esophageal squamous cell carcinoma. AB - This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the Editor in Chief. The term miR-143 has been used instead of the term miR-143* in the introduction and discussion which is misleading. With the misuse of this term subsequent errors and misleading statements appear throughout the paper. The authors apologize for this mistake. PMID- 26806811 TI - Vitamin B12 Deficiency in Infancy: The Case for Screening. AB - The classic principles put forth by Wilson and Jungner are often applied to determine the suitability of a condition for universal newborn screening. The three cases described here portray the harmful effects of vitamin B12 deficiency in infancy. The challenges and opportunities of early recognition and treatment are highlighted. Screening newborns would allow early detection and prevention of severe neurological damage in vitamin B12 -deficient infants and enable diagnosis of unrecognized maternal pernicious anemia in asymptomatic mothers. However, lack of standardized methodology and screening cutoffs present challenges to the use of current tandem mass spectrometry technologies for screening. PMID- 26806812 TI - Utility of Pilot Studies for Predicting Ratios and Intrasubject Variability in High-Variability Drugs. AB - Pilot studies can be used to identify adequate test formulations for pivotal bioequivalence trials. The objective of this study was to evaluate the usefulness of pilot studies in predicting ratios and the intrasubject coefficient of variation (CVw ) for pivotal studies of high-variability drugs. Seven cross-over and replicate bioequivalence trials were selected. A hundred simulations of pilot studies were performed for different sample sizes and designs. The pharmacokinetic data of the selected formulations were analysed using WinNonLin based on an analysis of variance (anova). The CVw was estimated using the formula recommended by the European Medicines Agency based on the mean square of the anova. We calculated the predictivity index +/- 10% and +/- 20% of the real value. The predictivity index of +/- 20% in the 2 * 2 design with 12 volunteers was 100% for AUC0-t ratio, 87% for Cmax ratio, 50% for the CVw of AUC0-t and 52% for the CVw of Cmax . The results of the 4 * 4 design with 8 volunteers were similar to those of the 2 * 2 design with 12 volunteers. These results were worse for the predictivity index of +/- 10% in both designs. Pilot studies do not seem useful for predicting sample size. However, they were very good for predicting the AUC0-t ratio and good for predicting the Cmax ratio. The most adequate design for pilot studies seems to be the 2 * 2 design with at least 12 volunteers. PMID- 26806813 TI - Primary spinal intramedullary malignant melanoma involving the medulla oblongata. PMID- 26806814 TI - Tetraparesis from cervical intracanal aneurysm of arteriovenous fistulae. PMID- 26806815 TI - Unstable transdiscal posterior fracture-subluxation. PMID- 26806816 TI - Oxygen transfer rates in shaken culture vessels from Fernbach flasks to microtiter plates. AB - By a sulfite oxidation method, oxygen transfer rates (OTRs) were determined in 11 types of culture vessels from 2.8-L Fernbach (FB) flasks to 96-, 48-, and 24-well square deepwell microtiter plates (MTPs). OTRs ranged from 140 mM/h in 250-mL UltrayieldTM flasks shaken at 300 rpm with a 50 mm diameter shaker throw to 5 mM/h in unbaffled FBs shaken at 200 rpm with a 25 mm throw. Baffles in FBs increased OTRs 6-12-fold under various shaking conditions, and up to five-fold in 250-mL flasks, depending on the type of baffles. Corner-baffling was superior to bottom-baffling in glass, 250-mL flasks. In MTPs, OTRs increased with increasing well size and decreasing fill volume. At 50 mm throw and 300 rpm, 24-well MTPs had OTRs comparable to corner-baffled, 250-mL flasks (~100 mM/h). The OTRs in unbaffled flasks were relatively insensitive to shaking conditions, increasing less than two-fold between the most modest and the most vigorous conditions. There was no consistency across vessels as to whether the alternate incubation conditions of 70 mm throw and 250 rpm produced higher OTRs than the 50 mm throw and 300 rpm regimen. No increase in OTR was seen in any MTP when the cover hole diameter was increased beyond 4.5 mm. OTRs decreased as viscosity increased, falling smoothly in unbaffled flasks and 24-well MTPs, but 48-well and 96-well MTPs showed precipitous OTR drops as viscosity increased. Matching the OTRs of screening vessels to the oxygen uptake rates of microbial cultures can greatly reduce the number of false positive strains that are forwarded from microbial screens. Biotechnol. Bioeng. 2016;113: 1729-1735. (c) 2016 Wiley Periodicals, Inc. PMID- 26806817 TI - An Integrated Methodology to Assess Compliance with Delphi Survey Key Components of Yoga Interventions for Musculoskeletal Conditions as Applied in a Systematic Review of Fibromyalgia Studies. AB - OBJECTIVE: The objective of this article was to present a methodology incorporating existing guidelines and tools for systematic reviews and to evaluate the Delphi survey 33 key component recommendations of yoga interventions for musculoskeletal conditions as a tool for a systematic review in fibromyalgia studies. DATA SOURCES: Databases searched included PubMed, Ovid Medline, PsychINFO, the Cochrane Library, CINAHL, ALT HealthWatch, PEDro, and Web of Science. ARTICLE SELECTION: Selected were articles published between November 14, 2004 and November 13, 2014, written in English, reporting original research of yoga interventions for adults with fibromyalgia. DATA EXTRACTION AND SYNTHESIS: Six articles met the inclusion criteria, revealing that three yoga styles ("Relaxing" yoga, Yoga of Awareness, and Hatha yoga) have been assessed in persons with fibromyalgia. Overall, reporting compliance with the 33 key components ranged from 39.4% to 84.8%, with a mean adherence rate of 62.63% +/- 17.74. None of the authors used an accepted reporting guideline; specific components of asana, pranayama, relaxation, and mindfulness practices that would have been incorporated into the interventions tested were identified in only 33.33% of the articles reviewed; and none of the articles included detailed, replicable descriptions of the interventions. CONCLUSIONS: This systematic review supports the need for comprehensive yoga research guidelines. Findings reveal a lack of reporting of intervention details, the need to report a disease-specific rationale for selection of the particular yoga style used for the intervention, and that a limited number of yoga styles have been investigated in persons with fibromyalgia. PMID- 26806819 TI - Evaluation of phytotoxicity effect on selected crops using treated and untreated wastewater from different configurative domestic wastewater plants. AB - This study investigated the phytotoxicity effect of untreated and treated wastewater collected from two different configurations of domestic wastewater treatment plants in South Africa. The phytotoxicity effect on vegetable seed growth was studied in terms of germination index (GI), relative seed germination (RSG) and relative root elongation (RRE) using four commercial crop varieties, viz., tomato (Lycopersicon esculentum), radish (Raphanus sativus), carrot (Daucus carota) and onion (Allium cepa). According to phyototoxicity limits, 80% germination and above is regarded as non-toxic and less than 50% GI is regarded as highly toxic and not suitable for agricultural purposes. In our study, seeds were irrigated with concentrations of 25%, 50%, 75%, 100% of treated effluent (TE) and untreated effluent (UTE). The TE results were best with the highest GI (%) recorded as tomato, 177; carrot, 158.5; onion, 132; and lettuce, 124. The results of this study indicate that TE showed no phytotoxicty effects and recorded above 80% GI. The UTE irrigated crops reached a GI of only 50% and above which is clear evidence of the beneficial effect of waste water treatment. The overall results confirmed that treated wastewater has a beneficial effect on agricultural crops and can be used as a liquid fertilizer. PMID- 26806818 TI - Characterization of hepatic stellate cells, portal fibroblasts, and mesothelial cells in normal and fibrotic livers. AB - BACKGROUND & AIMS: Contribution of hepatic stellate cells (HSCs), portal fibroblasts (PFs), and mesothelial cells (MCs) to myofibroblasts is not fully understood due to insufficient availability of markers and isolation methods. The present study aimed to isolate these cells, characterize their phenotypes, and examine their contribution to myofibroblasts in liver fibrosis. METHODS: Liver fibrosis was induced in Collagen1a1-green fluorescent protein (Col1a1(GFP)) mice by bile duct ligation (BDL), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet, or CCl4 injections. Combining vitamin A (VitA) lipid autofluorescence and expression of GFP and glycoprotein M6a (GPM6A), we separated HSCs, PFs, and MCs from normal and fibrotic livers by fluorescence-activated cell sorting (FACS). RESULTS: Normal Col1a1(GFP) livers broadly expressed GFP in HSCs, PFs, and MCs. Isolated VitA+ HSCs expressed reelin, whereas VitA-GFP+GPM6A- PFs expressed ectonucleoside triphosphate diphosphohydrolase-2 and elastin. VitA-GFP+GPM6A+ MCs expressed keratin 19, mesothelin, and uroplakin 1b. Transforming growth factor (TGF)-beta1 treatment induced the transformation of HSCs, PFs, and MCs into myofibroblasts in culture. TGF-beta1 suppressed cyclin D1 mRNA expression in PFs but not in HSCs and MCs. In biliary fibrosis, PFs adjacent to the bile duct expressed alpha-smooth muscle actin. FACS analysis revealed that HSCs are the major source of GFP+ myofibroblasts in the injured Col1a1(GFP) mice after DDC or CCl4 treatment. Although PFs partly contributed to GFP+ myofibroblasts in the BDL model, HSCs were still dominant source of myofibroblasts. CONCLUSION: HSCs, PFs, and MCs have distinct phenotypes, and PFs partly contribute to myofibroblasts in the portal triad in biliary fibrosis. PMID- 26806820 TI - Why should medical students study Social Gerontology? AB - The General Medical Council (GMC) provides a core curriculum for all medical degrees in the UK. However, these guidelines do not provide in-depth, specific learning outcomes for the various medical specialties. Recognising our ageing population, the British Geriatrics Society in 2013 published their own supplementary guidelines to encourage and further direct teaching on Gerontology and Geriatric Medicine in medical school curricula. Although teaching on Geriatric Medicine, a sub-discipline of Gerontology, has reassuringly increased in UK medical schools, there are convincing arguments for greater emphasis to be placed on the teaching of another sub-discipline: Social Gerontology. Considering the skills and knowledge likely to be gained from the teaching of Social Gerontology, in this paper we argue for the greater universal adoption of its teaching. This would help ensure that the doctors of tomorrow are better equipped to manage more successfully and holistically the growing cohort of older patients. PMID- 26806821 TI - Anterior chamber aqueous flare and optic nerve microcirculation in eyes with rhegmatogenous retinal detachment. PMID- 26806823 TI - "Saving Young Lives" with acute kidney injury: the challenge of acute dialysis in low-resource settings. PMID- 26806824 TI - Salt and health: time to revisit the recommendations. AB - The relationship between salt and human health has been the subject of controversy over the past century. The largest study in the field demonstrates a J-curve relationship between sodium intake and adverse clinical outcomes, suggesting a need to reevaluate current recommendations to restrict sodium intake to less than 2 g/d in the general population. PMID- 26806825 TI - A SPRINT to the finish, or just the beginning? Implications of the SPRINT results for nephrologists. AB - The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated a significant reduction in major cardiovascular events and all-cause mortality with intensive blood pressure control in older individuals at high cardiovascular risk, including patients with chronic kidney disease and mild proteinuria. Nephrologists should consider the SPRINT results when determining the optimal blood pressure target for patients with chronic kidney disease. PMID- 26806826 TI - Epithelial-to-mesenchymal transition of tubular epithelial cells in renal fibrosis: a new twist on an old tale. AB - Recent publications have questioned whether epithelial-to-mesenchymal transition of tubular epithelial cells is an important contributor to renal fibrosis. Two recent publications describe an intratubular epithelial-to-mesenchymal transition like program of epithelial cell dedifferentiation that may contribute to the recruitment or proliferation of interstitial myofibroblasts after kidney injury. PMID- 26806827 TI - Upregulation of AMWAP: a novel mechanism for HDAC inhibitors to protect against cisplatin nephrotoxicity. AB - Histone deacetylases have been reported to protect against renal tubular damage in several animal models of acute renal injury, including cisplatin nephrotoxicity. However, the mechanism involved is not well defined. In this study, Ranganathan et al. identify activated microglia/macrophage WAP domain protein as the novel mediator of histone deacetylase inhibitor-mediated renal protection in a murine model of cisplatin nephrotoxicity. Activated microglia/macrophage WAP-mediated renal protection is associated with suppression of inflammation and renal epithelial cell apoptosis. PMID- 26806828 TI - Concerted efforts to combat diabetic complications. AB - Kidney disease in diabetes is an important research topic in both clinical and basic science. Genetic analysis provides key translational data. In this regard, Jiang et al. emphasize some potential concerns over and problems with former genetics analysis methods, especially in common disease conditions such as kidney disease in diabetic patients. PMID- 26806829 TI - Angiopoietin-like protein 2 and kidney fibrosis: lessons from knockout mice. AB - The angiopoietin-like protein (ANGPTL) family is homologous to angiopoietins but does not bind to the Tie2 receptor. The function of ANGPTLs has been elucidated largely in the context of angiogenesis and lipid metabolism. Morinaga et al. demonstrated that genetic depletion of Angptl2 confers amelioration of the mouse kidney fibrosis induced by a unilateral ureteral obstruction, implicating that ANGPTL2, predominantly in the renal tubular compartments, activates the transforming growth factor-beta signaling and vice versa through miR-221. PMID- 26806830 TI - Epigenetic memory in kidney diseases. AB - Epigenetic mechanisms have been the focus of intensive research. De Marinis et al. demonstrated that high glucose levels exert stimulatory effects on activation histone marks, leading to the upregulation of thioredoxin-interacting protein (TXNIP) gene expression, which is proinflammatory. They also showed that the effect was reversed by the inhibition of histone acetyltransferase, suggesting a new therapeutic approach for improving diabetic kidney disease. Epigenetic changes are memorized as epigenetic memory that could exacerbate diabetic complications. PMID- 26806831 TI - Diagnosis of complement alternative pathway disorders. AB - Kidney diseases resulting from abnormal control of the complement alternative pathway include atypical hemolytic uremic syndrome, C3 glomerulonephritis, and dense-deposit disease, as well as atypical postinfectious glomerulonephritis. Although clinically diverse, they all result from loss of surface or fluid-phase complement control, caused by acquired or genetic defects in the complement alternative pathway. As such, the diagnostic approach is similar and includes a comprehensive biochemical, genetic, and pathologic analysis of the complement pathway. The biochemical test battery includes functional activity measurements of the entire complement pathway, functional and quantitative analysis of individual components and regulators, and quantification of activation products. In patients with a thrombotic microangiopathy, ADAMTS-13 activity should be determined to exclude a thrombotic thrombocytopenic purpura. The spectrum of genes currently known to be involved in the pathogenesis of alternative pathway disorders is rapidly expanding. Pathologic analysis of a kidney biopsy specimen is sophisticated with ad hoc immunofluorescence studies and laser microdissection with mass spectrometry. The identification of the underlying defect in the alternative pathway based on this comprehensive analysis will allow treatment to be directed to the site of dysregulation. PMID- 26806832 TI - Changing bone patterns with progression of chronic kidney disease. AB - It is commonly held that osteitis fibrosa and mixed uremic osteodystrophy are the predominant forms of renal osteodystrophy in patients with chronic kidney disease. Osteitis fibrosa is a high-turnover bone disease resulting mainly from secondary hyperparathyroidism, and mixed uremic osteodystrophy is in addition characterized by a mineralization defect most often attributed to vitamin D deficiency. However, there is ancient and more recent evidence that in early chronic kidney disease stages adynamic bone disease characterized by low bone turnover occurs first, at least in a significant proportion of patients. This could be due to the initial predominance of bone turnover-inhibitory conditions such as resistance to the action of parathyroid hormone (PTH), reduced calcitriol levels, sex hormone deficiency, diabetes, and, last but not least, uremic toxins leading to repression of osteocyte Wnt/beta-catenin signaling and increased expression of Wnt antagonists such as sclerostin, Dickkopf-1, and sFRP4. The development of high-turnover bone disease would occur only later on, when serum PTH levels are able to overcome peripheral PTH resistance and the other inhibitory factors of bone formation. Whether FGF23 and Klotho play a direct role in the transition from low- to high-turnover bone disease or participate only indirectly via regulating PTH secretion remains to be seen. PMID- 26806834 TI - Angiopoietin-like protein 2 increases renal fibrosis by accelerating transforming growth factor-beta signaling in chronic kidney disease. AB - Renal fibrosis is a common pathological consequence of chronic kidney disease (CKD) with tissue fibrosis closely associated with chronic inflammation in numerous pathologies. However, molecular mechanisms underlying that association, particularly in the kidney, remain unclear. Here, we determine whether there is a molecular link between chronic inflammation and tissue fibrosis in CKD progression. Histological analysis of human kidneys indicated abundant expression of angiopoietin-like protein 2 (ANGPTL2) in renal tubule epithelial cells during progression of renal fibrosis. Numerous ANGPTL2-positive renal tubule epithelial cells colocalized with cells positive for transforming growth factor (TGF)-beta1, a critical mediator of tissue fibrosis. Analysis of M1 collecting duct cells in culture showed that TGF-beta1 increases ANGPTL2 expression by attenuating its repression through microRNA-221. Conversely, ANGPTL2 increased TGF-beta1 expression through alpha5beta1 integrin-mediated activation of extracellular signal-regulated kinase. Furthermore, ANGPTL2 deficiency in a mouse unilateral ureteral obstruction model significantly reduced renal fibrosis by decreasing TGF beta1 signal amplification in kidney. Thus, ANGPTL2 and TGF-beta1 positively regulate each other as renal fibrosis progresses. Our study provides insight into molecular mechanisms underlying chronic inflammation and tissue fibrosis and identifies potential therapeutic targets for CKD treatment. PMID- 26806835 TI - Epigenetic regulation of the thioredoxin-interacting protein (TXNIP) gene by hyperglycemia in kidney. AB - Diabetic kidney disease is the leading cause of end-stage renal disease. Genetic factors have been suggested to contribute to its susceptibility. However, results from genetic studies are disappointing possibly because the role of glucose in diabetic kidney disease predisposed by epigenetic mechanisms has not been taken into account. Since thioredoxin-interacting protein (TXNIP) has been shown to play an important role in the pathogenesis of diabetic kidney disease, we tested whether glucose could induce expression of TXNIP in the kidney by epigenetic mechanisms. In kidneys from diabetic Sur1-E1506K(+/+) mice, hyperglycemia-induced Txnip expression was associated with stimulation of activating histone marks H3K9ac, H3K4me3, and H3K4me1, as well as decrease in the repressive histone mark H3K27me3 at the promoter region of the gene. Glucose also coordinated changes in histone marks and TXNIP gene expression in mouse SV40 MES13 mesangial cells and the normal human mesangial cell line NHMC. The involvement of histone acetylation in glucose-stimulated TXNIP expression was confirmed by reversing or enhancing acetylation using the histone acetyltransferase p300 inhibitor C646 or the histone deacetylase inhibitor trichostatin A. Thus, glucose is a potent inducer of histone modifications, which could drive expression of proinflammatory genes and thereby predispose to diabetic kidney disease. PMID- 26806833 TI - The molecular mechanisms of hemodialysis vascular access failure. AB - The arteriovenous fistula has been used for more than 50 years to provide vascular access for patients undergoing hemodialysis. More than 1.5 million patients worldwide have end stage renal disease and this population will continue to grow. The arteriovenous fistula is the preferred vascular access for patients, but its patency rate at 1 year is only 60%. The majority of arteriovenous fistulas fail because of intimal hyperplasia. In recent years, there have been many studies investigating the molecular mechanisms responsible for intimal hyperplasia and subsequent thrombosis. These studies have identified common pathways including inflammation, uremia, hypoxia, sheer stress, and increased thrombogenicity. These cellular mechanisms lead to increased proliferation, migration, and eventually stenosis. These pathways work synergistically through shared molecular messengers. In this review, we will examine the literature concerning the molecular basis of hemodialysis vascular access malfunction. PMID- 26806837 TI - Crystal-storing histiocytosis. PMID- 26806836 TI - Genetic and clinical variables identify predictors for chronic kidney disease in type 2 diabetes. AB - Type 2 diabetes and chronic kidney disease (CKD) may share common risk factors. Here we used a 3-stage procedure to discover novel predictors of CKD by repeatedly applying a stepwise selection based on the Akaike information criterion to subsamples of a prospective complete-case cohort of 2755 patients. This cohort encompassed 25 clinical variables and 36 genetic variants associated with type 2 diabetes, obesity, or fasting plasma glucose. We compared the performance of the clinical, genetic, and clinico-genomic models and used net reclassification improvement to evaluate the impact of top selected genetic variants to the clinico-genomic model. Associations of selected genetic variants with CKD were validated in 2 independent cohorts followed by meta-analyses. Among the top 6 single-nucleotide polymorphisms selected from clinico-genomic data, three (rs478333 of G6PC2, rs7754840 and rs7756992 of CDKAL1) contributed toward the improvement of prediction performance. The variant rs478333 was associated with rapid decline (over 4% per year) in estimated glomerular filtration rate. In a meta-analysis of 2 replication cohorts, the variants rs478333 and rs7754840 showed significant associations with CKD after adjustment for conventional risk factors. Thus, this novel 3-stage approach to a clinico-genomic data set identified 3 novel genetic predictors of CKD in type 2 diabetes. This method can be applied to similar data sets containing clinical and genetic variables to select predictors for clinical outcomes. PMID- 26806838 TI - An unusual cause of hematuria. PMID- 26806839 TI - The Case | A man with hypertension, respiratory distress, and rapidly progressive renal failure. PMID- 26806840 TI - Screening for Cardiac Magnetic Resonance Scar Features by 12-Lead ECG, in Patients with Preserved Ejection Fraction. AB - BACKGROUND: Increased QRS score and wide spatial QRS-T angle are independent predictors of cardiovascular mortality in the general population. Our main objective was to assess whether a QRS score >= 5 and/or QRS-T angle >= 105 degrees enable screening of patients for myocardial scar features. METHODS: Seventy-seven patients of age <= 70 years with QRS score >= 5 and/or spatial QRS T angle >= 105 degrees as well as left ventricular ejection fraction (LVEF) >35% were enrolled in the study. All participants underwent complete clinical examination, signal-averaged ECG (SAECG), 30-minute ambulatory ECG recording for T-wave alternans (TWA), and late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Relationship between QRS score, QRS-T angle with scar presence and pattern, as well as gray zone, core, and total scar size by LGE-CMR were assessed. RESULTS: Myocardial scar was present in 41 (53%) patients, of whom 19 (46%) exhibited a typical ischemic pattern. QRS score but not QRS-T angle was related to total scar size and gray zone size (R(2) = 0.12, P = 0.002; R(2) = 0.17; P <= 0.0001, respectively). Patients with QRS scores >= 6 had significantly greater myocardial scar and gray zone size, increased QRS duration and QRS-T angle, a higher prevalence of late potentials (LPs) presence, increased LV end diastolic volume and decreased LVEF. There was a significant independent and positive association between TWA value and total scar (P = 0.001) and gray zone size (P = 0.01). CONCLUSION: Patients with preserved LVEF and myocardial scar by CMR also have electrocardiographic features that could be involved in ventricular arrhythmogenesis. PMID- 26806841 TI - Phylogeographic analysis of severe fever with thrombocytopenia syndrome virus from Zhoushan Islands, China: implication for transmission across the ocean. AB - From June 2011 to August 2014, 21 cases of infection by severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) were confirmed in Zhoushan Islands in the Eastern coast of China. To identify the source of SFTSV in Zhoushan Islands, the whole SFTSV genomes were amplified and sequenced from 17 of 21 patients. The L, M, and S genomic segments of these SFTSV strains were phylogenetically analyzed together with those of 188 SFTSV strains available from GenBank. Phylogenetic analysis demonstrated SFTSV could be classified into six genotypes. The genotypes F, A, and D were dominant in mainland China. Additionally, seven types of SFTSV genetic reassortants (abbreviated as AFA, CCD, DDF, DFD, DFF, FAF, and FFA for the L, M and S segments) were identified from 10 strains in mainland China. Genotype B was dominant in Zhoushan Islands, Japan and South Korea, but not found in mainland China. Phylogeographic analysis also revealed South Korea possible be the origin area for genotype B and transmitted into Japan and Zhoushan islands in the later part of 20(th) century. Therefore, we propose that genotype B isolates were probable transmitted from South Korea to Japan and Zhoushan Islands. PMID- 26806842 TI - Can lung ultrasonography predict prone positioning response in acute respiratory distress syndrome patients? AB - PURPOSE: The purpose was to assess whether lung ultrasonography (L-US) is a useful tool in prediction of prone positioning (PP) oxygenation response in patients with acute respiratory distress syndrome (ARDS). METHODS: In a prospective study, 19 ARDS patients were included for assessment of PP oxygenation response. The latter was assessed for at least 12 hours 6 different ultrasonography windows were performed on each hemithorax before prone (H0, H2, H12 before return to supine and at H14 (2 hours after return to supine). Patients were classified into 2 groups (responders / non responders) according their oxygenation response to PP. Ultrasonography videos were blindly evaluated by 3 expert clinicians to classify lung regions as "normal", "moderate loss of aeration," "severe loss of aeration," or "lung consolidation." Oxygenation parameters were collected at H0, H2, and H14. RESULTS: Association of each lung region aspect to PP oxygenation response was compared between the 2 groups. The normal aspect of the anterobasal regions was significantly associated with the oxygenation response (P = .0436), with a positive predictive value equal to or near 100%. DISCUSSION: Our results demonstrated that a simple and short L-US examination could be a useful tool in prediction of PP oxygenation response in ARDS patients. A normal L-US pattern of both anterobasal lung regions in supine position may predict a significant PaO2/FIO2 ratio improvement. PMID- 26806844 TI - The electrooxidation-induced structural changes of gold di-superatomic molecules: Au23vs. Au25. AB - The gold cluster compounds Au38(SC2H4Ph)24 and [Au25(PPh3)10(SC2H4Ph)5Cl2](2+) are known to possess bi-icosahedral Au23 and Au25 cores, respectively, inside their ligand shells. These Au cores can be viewed as quasi-molecules composed of two Au13 superatoms sharing three and one Au(+) atoms, respectively. In the present work, we studied the structural changes of these gold di-superatomic molecules upon electrooxidation via spectroelectrochemical techniques, X-ray absorption fine structure analysis, and density functional theory calculations. The Au23 core was electrochemically stable, but the Au25 core underwent irreversible structural change. This marked difference in the stability of the oxidized states is ascribed to differences in the bonding scheme of Au13 units and/or the bonding nature of the protecting ligands. PMID- 26806845 TI - A novel reactive epitope-based antigen targeted by serum autoantibodies in oligoarticular and polyarticular juvenile idiopathic arthritis and development of an electrochemical biosensor. AB - Currently, there are no specific markers for juvenile idiopathic arthritis (JIA) diagnosis, which is based on clinical symptoms and some blood tests for diseases' exclusion. Aiming to select new epitope-based antigens (mimotopes) that could recognize circulating autoantibodies in most JIA forms, we screened a phage displayed random peptide library against IgG antibodies purified from serum of JIA patients. ELISA assay was carried out to confirm immunoreactivity of selected peptides against sera IgG antibodies from JIA patients, healthy children and patients with other autoimmune diseases. The mimotope PRF+1 fused to phage particles was able to efficiently discriminate JIA patients from controls, and for this reason was chosen to be chemically synthesized for validation in a larger sample size. The synthetic peptide was immobilized onto bioelectrodes' surface for antibody detection by electrochemical analyses through differential pulse voltammetry. The PRF+1 synthetic peptide has efficiently discriminated JIA patients from control groups (p<0.0001) with a very good accuracy (AUC>0.84; sensitivity=61%; specificity=91%). The electrochemical platform proved to be fast, low cost and effective in detecting anti-PRF+1 antibodies from JIA patients compared to healthy controls (p=0.0049). Our study describes a novel and promising epitope-based biomarker for JIA diagnosis that can become a useful tool for screening tests, which was successfully incorporated onto an electrochemical biosensor and could be promptly used in field diagnostics. PMID- 26806846 TI - Doing What You're Told: It's Not That Simple. PMID- 26806847 TI - Entecavir Treatment in Children and Adolescents with Chronic Hepatitis B Virus Infection. AB - BACKGROUND: The aim of this study was to investigate the treatment response of entecavir (ETV) in children and adolescents with chronic hepatitis B (CHB) who acquired infection perinatally or during early childhood. METHODS: A total of nine treatment-naive patients [median aged 12.2 years (range: 2.6-18.0); five girls and four boys], with hepatitis B e antigen (HBeAg) seropositive > 6 months, alanine aminotransferase (ALT) > 2 times of upper limit of normal value (30 IU/L), were enrolled for ETV therapy. They received ETV therapy with a dose of 0.015 mg/kg/d, with a maximal dose of 0.5 mg daily for at least 52 weeks. Another 27 untreated CHB patients matched for age, sex, ALT levels, and HBeAg status were recruited as the control group. A complete response at 48-52 weeks was defined as follows: (1) normalization of ALT; (2) undetectable hepatitis B virus DNA; and (3) HBeAg/anti-HBe seroconversion. All 36 patients were retrospectively reviewed for their biochemical, serological, and virologic responses. RESULTS: ETV-treated patients achieved rapid ALT normalization (all before 8 months of treatment) compared with the control group (p < 0.001) and they had a greater chance of achieving undetectable HBV DNA levels at Week 52 after treatment (55.6% vs. 11.1%, p = 0.013). The cumulative incidence rates of HBeAg seroconversion were similarly high in both groups (ETV group 44% at 1 year 78% at 2 years; control group 37% at 1 year 63% at 2 years, respectively). The ETV group also had a trend of better complete response than the control group (22.2% vs. 0%, p = 0.057). None of the ETV-treated patients reported significant adverse effects. CONCLUSION: Entecavir for pediatric CHB treatment is safe and shows clinical benefits in short-term biochemical and virologic responses. Further studies to determine long-term remission and drug resistance are required. PMID- 26806848 TI - Aminophylline Therapy and the Neurodevelopment in Premature Infants. PMID- 26806850 TI - Azulenesulfonium Salts: Accessible, Stable, and Versatile Reagents for Cross Coupling. AB - Azulenesulfonium salts may be readily prepared from the corresponding azulenes by an SE Ar reaction. These azulene sulfonium salts are bench-stable species that may be employed as pseudohalides for cross-coupling. Specifically, their application in Suzuki-Miyaura reactions has been demonstrated with a diverse selection of coupling partners. These azulenesulfonium salts possess significant advantages in comparison with the corresponding azulenyl halides, which are known to be unstable and difficult to prepare in pure form. PMID- 26806849 TI - A Bayesian framework systematic review and meta-analysis of anesthetic agents effectiveness/tolerability profile in electroconvulsive therapy for major depression. AB - The aim of this study was to assess the efficacy and tolerability/acceptability of 6 anesthetic agents in ECT for depressive disorders. We systematically reviewed 14 double-blind randomized controlled trials (610 participants). Efficacy was measured by the mean scores on validated depression scales at 6 ECT (or the nearest score if not available), number of responders at the end of treatment and seizure duration. The acceptability was measured by the proportion of patients who dropped out of the allocated treatment, and the tolerability by the number of serious adverse events and post-treatment cognition assessment. After excluding the trials responsible for heterogeneity, depression scores of patients who were administered methohexital were found to be significantly more improved than those who received propofol (p = 0.001). On the contrary, those who were administered propofol had lower depression scores than those with thiopental at the end of treatment (p = 0.002). Compared to propofol, methohexital was found to be significantly associated with higher seizure duration (p = 0.018). No difference was found for the acceptability profile (all p > 0.05). In summary, ketamine and methohexital may be preferred to propofol or thiopental in regard of effectiveness in depression scores and increased seizure duration. Further studies are warranted to compare ketamine and methohexital. PMID- 26806851 TI - Acute Methanol Poisoning: Prevalence and Predisposing Factors of Haemorrhagic and Non-Haemorrhagic Brain Lesions. AB - The purpose was to study the prevalence and predisposing factors of brain lesions in survivors of acute methanol poisoning. Clinical data on 106 patients with methanol poisoning were collected during the Czech mass poisoning outbreak. Of 83 survivors, in 46 (55%) patients, follow-up examinations including magnetic resonance imaging of brain (MR) were performed 3-8 and 24-28 months after discharge from the hospital. Of 46 patients with a median age of 49 (interquartile range, 35-57) years, 24 (52%) patients had a total of 40 abnormal brain findings with haemorrhagic lesions detected in 15 (33%) and non haemorrhagic lesions found in 9 (19%) patients. The patients with haemorrhagic brain lesions were more acidemic (lower arterial blood pH, higher base deficit) and had higher glycaemia and lactacidaemia on admission than those without haemorrhages (all p < 0.05). Thirteen of 32 (41%) of patients with systemic anticoagulation and 2 of 14 (14%) of patients without it had haemorrhagic lesions (p = 0.080). Bleeding complications during the treatment occurred in 4 of 15 (27%) patients, and 5 of 15 (33%) patients had conditions predisposing to haemorrhage in the group with haemorrhagic lesions. In three cases with a series of computer tomography (CT)/MR performed during hospitalization, the necrotic lesions in the brain remained non-haemorrhagic during hospitalization and haemorrhagic lesions were detected on the follow-up MR examinations only. No association between brain haemorrhages and systemic anticoagulation during dialysis was found: brain haemorrhages might occur in severely poisoned patients treated without systemic anticoagulation, whereas treatment with high doses of heparin might not lead to brain haemorrhages. PMID- 26806854 TI - Short-Interval Retreatment With Stereotactic Body Radiotherapy (SBRT) for Pediatric Neuroblastoma Resulting in Severe Myositis. AB - We report a severe and not previously reported toxicity after short-interval retreatment with stereotactic body radiotherapy (SBRT) in a pediatric patient with neuroblastoma. This patient experienced Grade III radiation myositis after treatment with conventional radiation therapy followed by high-dose SBRT for persistent disease a short interval after the initial radiotherapy course. While SBRT shows outstanding rates of local control in adult disease, data in pediatric cancers are extremely limited. In this report, we discuss the rationale of SBRT in this patient's multimodality neuroblastoma treatment, management of the toxicity, and future perspectives on the use of SBRT in pediatric cancer. PMID- 26806853 TI - An in vitro compartmentalization-based method for the selection of bond-forming enzymes from large libraries. AB - We have developed a generalized in vitro compartmentalization-based bead display selection strategy that allows for the identification of enzymes that can perform ligation reactions. Although a number of methods have been developed to evolve such enzymes, many of them are limited in library size (10(6) -10(7) ), do not select for enzymes using a scheme that allows for multiple turnover, or only work on enzymes specific to nucleic acids. This approach is amenable to screening libraries of up to 10(12) protein variants by allowing beads to be overloaded with up to 10(4) unique mutants. Using this approach we isolated a variant of sortase A from Staphylococcus aureus that shows a 114-fold enhancement in kcat /KM in the absence of calcium compared to the wild-type and improved resistance to the inhibitory effects of cell lysates. Unlike the wild-type protein, the newly selected variant shows intracellular activity in the cytoplasm of eukaryotic cells where it may prove useful for intracellular labeling or synthetic biological applications. Biotechnol. Bioeng. 2016;113: 1647-1657. (c) 2016 Wiley Periodicals, Inc. PMID- 26806855 TI - Autophagy-related gene 5 and Wnt5 signaling pathway requires differentiation of embryonic stem cells into odontoblast-like cells. AB - We previously confirmed a unique and unanticipated role for an alpha2 integrin, extracellular matrix metalloproteinase inducer (Emmprin), and matrix metalloproteinase (MMP)-3-mediated signaling cascade, in driving the odontoblast like differentiation of mouse embryonic stem (ES) cells in a collagen type-I scaffold (CS) combined with bone morphogenetic protein (BMP)-4 (CS/BMP-4). To explore the early signaling cascade for odontoblastic differentiation, we examined the upregulation of autophagy-related gene (Atg) and Wnt signaling by CS/BMP-4 mediated odontoblast differentiation. In a screening experiment, CS/BMP 4 increased the mRNA and protein levels of Atg5, Lrp5/Fzd9 (an Atg5 receptor), and Wnt5, but not microtubule-associated protein 1 light chain (LC3; a mammalian homolog of yeast Atg8), TFE3, Beclin1, and Atg12, together with the amount of autophagosomes and autophagy fluxes. Treatment with siRNAs against Atg5 and Wnt5 individually suppressed the CS/BMP-4-induced increase in odontoblast differentiation. The odontoblastic phenotype, involving dentin matrix protein-1 and dentin sialophosphoprotein expression, decreased when autophagy was inhibited by chloroquine, but increased after treatment with rapamycin (an autophagy enhancer). Taken together with our previous findings, we have revealed a unique sequential cascade involving Atg5, Wnt5a, alpha2 integrin, Emmprin, and MMP-3. This cascade results in a potent increase in odontoblastic cell differentiation, indicating the unique involvement of Atg5, autophagy and Wnt5 signaling in CS/BMP 4-induced differentiation of ES cells into odontoblast-like cells, at a relatively early stage. PMID- 26806856 TI - Impact of particle elasticity on particle-based drug delivery systems. AB - Modification of nano/micro-particle physical parameters (e.g. size, shape, surface charge) has proven to be an effective method to enhance their delivery abilities. Recently, advances in particle synthesis have facilitated investigations into the role that particle elasticity plays in modulating drug delivery processes. This review will highlight: (i) methods to tune particle elasticity, (ii) the role particle elasticity plays in cellular internalization, (iii) the role of particle elasticity in modulating circulation times, (iv) the effect of particle elasticity on altering biodistribution and tissue targeting, and (v) the application of computational methods to explain the differences in cellular internalization of particles of different elasticities. Overall, literature reports suggest a complex relationship between particle elasticity and drug delivery processes. Despite this complex relationship, it is clear from numerous in vitro and in vivo studies that particle elasticity is an important parameter that can be leveraged to improve blood circulation, tissue targeting, and specific interactions with cells. PMID- 26806857 TI - Intra-individual stability and developmental change in hair cortisol among postpartum mothers and infants: Implications for understanding chronic stress. AB - The study goal was to determine the intra-individual stability, developmental change, and maternal-reported correlates (socio-demographic, stress experiences, hair characteristics, and care) of hair cortisol in mothers and their infants. To assess cortisol deposition in hair during the periods of 6-to-9 months and 9-to 12 months of age, 3 cm segments of hair samples deemed to represent approximately 3 months of retrospective hair cortisol were sampled longitudinally at 9- and 12 months in 41 mothers and infants. Bivariate correlations and mean level comparisons of log-transformed hair cortisol levels at 9- (T1) and 12-months (T2) in mothers and infants were examined. Hair cortisol values were positively correlated from T1 to T2 for mothers (r = .41, p < .05) and infants (r = .39, p < .05). Hair cortisol values did not significantly differ from T1 to T2 in infants but decreased for mothers (F(1,34) = 9.2, p < .01). Maternal and infant hair cortisol was not associated with each other at either time point. Self-reported measures of stress, and hair characteristics and care were not associated with hair cortisol. This is the first study to obtain hair cortisol from more than one time point within the first year after birth in mothers and infants. The intra individual stability of hair cortisol suggests that it may be a possible biomarker for detecting change in chronic stress experiences within the first year of life and in the postpartum period. PMID- 26806858 TI - Examination of England's New Medicine Service (NMS) of complex health care interventions in community pharmacy. AB - BACKGROUND: Community pharmacies are increasingly commissioned to deliver new, complex health interventions in response to the growing demands on family doctors and secondary health care services. Little is known about how these complex interventions are being accommodated and translated into the community pharmacy setting and whether their aims and objectives are realized in practice. The New Medicine Service (NMS) is a complex medicine management intervention that aims to support patients' adherence to newly prescribed medicines for a long-term condition. OBJECTIVE: This study explores the recent implementation of the NMS in community pharmacies across England. It also seeks to understand how the service is becoming manifest in practice and what lessons can be learned for future service implementation. METHODS: Structured, organizational ethnographic observations and in situ workplace interviews with pharmacists and support staff were undertaken within 23 English community pharmacies. Additionally, one-to-one, semi-structured interviews were carried out with 47 community pharmacists and 11 general practitioners (GPs). Observational and interview data were transcribed and analyzed thematically and guided by Damschroder's consolidated framework for implementation research. RESULTS: The NMS workload had been implemented and absorbed into pharmacists' daily routines alongside existing responsibilities with no extra resources and little evidence of reduction in other responsibilities. Pharmacists were pragmatic, simplifying, and adapting the NMS to facilitate its delivery and using discretion to circumvent perceived non essential paperwork. Pharmacist understanding of the NMS was found to impact on what they believed should be achieved from the service. Despite pharmacists holding positive views about the value of the NMS, not all were convinced of its perceived benefits and necessity, with reports that many consultations did not identify any problems with the patients' medicines. GPs were generally supportive of the initiative but were unaware of the service or potential benefits. Poorly developed existing pharmacist-GP relationships impeded implementation. CONCLUSIONS: This study identifies the multifaceted and complex processes involved in implementing a new community pharmacy service in England. Community pharmacy workflow, infrastructure, and public and professional relationships all affect NMS implementation. Greater prior engagement with the pharmacy workforce and GPs, robust piloting and a phased rollout together with ongoing support and updates, are potentials strategies to ensure future implementation of pharmacy services meet their intended aims in practice. PMID- 26806862 TI - Exposure to blue wavelength light modulates anterior cingulate cortex activation in response to 'uncertain' versus 'certain' anticipation of positive stimuli. AB - Blue wavelength light has been used as an effective treatment for some types of mood disorders and circadian rhythm related sleep problems. We hypothesized that acute exposure to blue wavelength light would directly affect the functioning of neurocircuity implicated in emotion regulation (i.e., ventromedial prefrontal cortex, amygdala, insula, and anterior cingulate cortex [ACC]) during 'certain' and 'uncertain' anticipation of negative and positive stimuli. Thirty-five healthy adults were randomized to receive a thirty-minute exposure to either blue (active) or amber (placebo) light, immediately followed by an emotional anticipation task during functional magnetic resonance imaging (fMRI). In contrast to placebo, participants in the blue light group showed significantly reduced activation within the rostral ACC during 'uncertain' anticipation (i.e., uncertainty regarding whether a positive or negative stimulus would be shown) in comparison to 'certain' anticipation of a positive stimulus. These findings may be explicable in terms of interactions between blue light exposure and the influence of specific neuromodulators on ACC-mediated decision-making mechanisms. PMID- 26806863 TI - Val66Met BDNF polymorphism is associated with Parkinson's disease cognitive impairment. AB - Parkinson's disease (PD) is one of the most common neurodegenerative diseases worldwide. Besides characteristic PD motor features, the disease has important non-motor characteristics such as cognitive impairment. The role of genetic factors in cognitive impairment associated with PD is still unclear. In this study, we examined whether BDNF Val66Met was associated with impaired cognition in Parkinson's disease. One hundred and seventy five patients with a clinical diagnosis of Parkinson's disease were included. Global cognitive abilities of the patients were measured by the Mini-Mental State Examination (MMSE). Poisson Regression models were used to test for association between 66Met carriers and cognitive impairment controlling for covariates. Carriers of at least one BDNF 66Met allele presented a higher prevalence of cognitive impairment (p=0.005 RR=1.45 IC=95% [1.1-1.8]). These results suggest a role for BDNF Val66Met polymorphism on cognitive impairment in PD. PMID- 26806859 TI - Prescription drug abuse communication: A qualitative analysis of prescriber and pharmacist perceptions and behaviors. AB - BACKGROUND: Interpersonal communication is inherent in a majority of strategies seeking to engage prescriber and pharmacist health care professionals (HCPs) in the reduction and prevention of prescription drug abuse (PDA). However, research on HCP PDA communication behavioral engagement and factors that influence it is limited. OBJECTIVES: This study quantitatively examined communication behaviors and trait-level communication metrics, and qualitatively described prescription drug abuse-related communication perceptions and behaviors among primary care prescribers and community pharmacists. METHODS: Five focus groups (N = 35) were conducted within the Appalachian Research Network (AppNET), a rural primary care practice-based research network (PBRN) in South Central Appalachia between February and October, 2014. Focus groups were structured around the administration of three previously validated trait-level communication survey instruments, and one instrument developed by the investigators to gauge HCP prescription drug abuse communication engagement and perceived communication importance. Using a grounded theory approach, focus group themes were inductively derived and coded independently by study investigators. Member-checking interviews were conducted to validate derived themes. RESULTS: Respondents' trait level communication self-perceptions indicated low communication apprehension, high self-perceived communication competence, and average willingness to communicate as compared to instrument specific criteria and norms. Significant variation in HCP communication behavior engagement was noted specific to PDA. Two overarching themes were noted for HCP-patient communication: 1) influencers of HCP communication and prescribing/dispensing behaviors, and 2) communication behaviors. Multiple sub-themes were identified within each theme. Similarities were noted in perceptions and behaviors across both prescribers and pharmacists. CONCLUSIONS: Despite the perceived importance of engaging in PDA communication, HCPs reported that prescription drug abuse communication is uncomfortable, variable, multifactorial, and often avoided. The themes that emerged from this analysis support the utility of communication science and health behavior theories to better understand and improve PDA communication behaviors of both prescribers and pharmacists, and thereby improve engagement in PDA prevention and treatment. PMID- 26806864 TI - Visualizer cognitive style enhances visual creativity. AB - In the last two decades, interest towards creativity has increased significantly since it was recognized as a skill and as a cognitive reserve and is now always more frequently used in ageing training. Here, the relationships between visual creativity and Visualization-Verbalization cognitive style were investigated. Fifty college students were administered the Creative Synthesis Task aimed at measuring the ability to construct creative objects and the Visualization Verbalization Questionnaire (VVQ) aimed at measuring the attitude to preferentially use either imagery or verbal strategy while processing information. Analyses showed that only the originality score of inventions was positively predicted by the VVQ score: higher VVQ score (indicating the preference to use imagery) predicted originality of inventions. These results showed that the visualization strategy is involved especially in the originality dimension of creative objects production. In light of neuroimaging results, the possibility that different strategies, such those that involve motor processes, affect visual creativity is also discussed. PMID- 26806865 TI - Serum miR-132 is a risk marker of post-stroke cognitive impairment. AB - BACKGROUND/AIMS: Recently, it has been reported that the microRNA-132(miR-132) is linked with synaptic plasticity and cognitive impairment. The present study investigates that whether miR-132 is altered in circulating blood serum samples of post-stroke cognitive impairment (PSCI) patients. METHODS: We collected samples from 39 subjects with PSCI, 37 subjects with post-stroke cognitive normality (PSCN), and 38 age-matched controls (AMC) for which ages, gender and education level were matched. MiR-132 was detected using a quantitative real-time PCR (qRT-PCR) method. To test the predictive value of miR-132 for PSCI, prediction capabilities were compared using the receiver operating characteristic (ROC) curves and area under curve (AUC) analysis. RESULTS: The level of miR-132 in PSCI patient serum was significantly elevated compared to that of PSCN and AMC subjects. The ROC curve showed that miR-132 achieved an AUC of 0.961 (p<0.0001). Importantly, the miR-132 level was correlated with the Montreal Cognitive Assessment (MoCA) score in PSCI patients. CONCLUSIONS: These results indicated that there was a substantial correlation between serum miR-132 expression and post-stroke cognitive functionality, suggesting that miR-132 may be a risk marker for PSCI. Because of the limitations of this study, the results should be treated with caution. PMID- 26806866 TI - Association of the MTHFR rs1801131 and rs1801133 variants in sporadic Parkinson's disease patients. AB - Parkinson's disease (PD) is a common age-dependent neurodegenerative movement disorder related to multiple factors, and genetic factors play an important role in the pathogenesis of PD. Variants in the methylenetetrahydrofolate reductase gene (MTHFR), a gene encoding a folate-dependent enzyme that is involved in homocysteine metabolism, have been reported to be associated with PD. To explore the role of the MTHFR gene in the development of PD in Chinese Han population, we analyzed two MTHFR variants (rs1801131 and rs1801133) in a patient cohort consisting of 512 patients with PD from mainland China and a control cohort consisting of 512 age, gender and ethnicity matched normal subjects. Statistically significant differences in genotypic and allelic frequencies were detected in the MTHFR variant rs1801133 (P=0.022 and 0.007, respectively; odds ratio=0.780, 95% confidence interval=0.651-0.934). In addition, the A-T haplotype of rs1801131-rs1801133 showed a protective role against PD development (P=0.007, odds ratio=0.779, 95% confidence interval=0.650-0.933). Our results suggested that the T allele of rs1801133 variant and A-T haplotype of rs1801131-rs1801133 in the MTHFR gene may decrease the risk of developing PD in Chinese Han population from mainland China. PMID- 26806867 TI - Expression changes of genes associated with apoptosis and survival processes in Parkinson's disease. AB - Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of the dopaminergic neurons in substantia nigra, presumably due to increased apoptosis and oxidative stress. To investigate whether PD-induced survival/apoptosis gene expression changes can serve as prognostic biomarkers of PD, we measured expression levels of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt pathway factors and additional apoptotic and anti-apoptotic factors in peripheral blood mononuclear cells (PBMC) of PD patients (n=50) and healthy controls (n=50) by real time PCR. Expression levels of apoptotic factors phosphatase and tensin homolog (PTEN) and mitochondrial apoptosis-inducing factor 1 (AIFM1) were significantly decreased, anti-apoptotic factors DJ-1 and Akt-1 were significantly increased and anti apoptotic Bcl-2 was significantly decreased in PD patients. Expression levels of AIFM1 were significantly correlated with Hoehn-Yahr scores. Moreover, PD patients with postural instability showed significantly reduced expression levels of anti apoptotic DJ-1, Akt-1 and mTOR than PD patients without postural instability. Expression profiles of brain samples of mice with rotenone-induced PD model and PBMC samples of PD patients showed remarkable resemblance. Our results indicate that the anti-apoptotic PI3K/Akt pathway is over activated in PD, presumably as an effort to compensate for increased neuronal apoptosis and oxidative stress. By contrast, patients with postural instability show reduced anti-apoptotic factor expression suggesting that this compensating mechanism fails in patients with this particular motor symptom. PBMC expression levels of AIFM1 might serve as a biomarker of disability and disease progression in PD. PMID- 26806868 TI - Resistive Switching Memory Phenomena in PEDOT PSS: Coexistence of Switchable Diode Effect and Write Once Read Many Memory. AB - We study resistive switching memory phenomena in conducting polymer PEDOT PSS. In the same film, there are two types of memory behavior coexisting; namely, the switchable diode effect and write once read many memory. This is the first report on switchable diode phenomenon based on conducting organic materials. The effect was explained as charge trapping of PEDOT PSS film and movement of proton. The same PEDOT PSS device also exhibits write once read many memory (WORM) phenomenon which arises due to redox reaction that reduces PEDOT PSS and renders it non conducting. The revelation of these two types of memory phenomena in PEDOT PSS highlights the remarkable versatility of this conducting conjugated polymer. PMID- 26806870 TI - Acute fluoxetine exposure alters crab anxiety-like behaviour, but not aggressiveness. AB - Aggression and responsiveness to noxious stimuli are adaptable traits that are ubiquitous throughout the animal kingdom. Like vertebrate animals, some invertebrates have been shown to exhibit anxiety-like behaviour and altered levels of aggression that are modulated by the neurotransmitter serotonin. To investigate whether this influence of serotonin is conserved in crabs and whether these behaviours are sensitive to human antidepressant drugs; the striped shore crab, Pachygrapsus crassipes, was studied using anxiety (light/dark test) and aggression (mirror test) paradigms. Crabs were individually exposed to acute doses of the selective serotonin reuptake inhibitor, fluoxetine (5 or 25 mg/L), commonly known as Prozac(r), followed by behavioural testing. The high dose of fluoxetine significantly decreased anxiety-like behaviour but had no impact on mobility or aggression. These results suggest that anxiety-like behaviour is more sensitive to modulation of serotonin than is aggressiveness in the shore crab. PMID- 26806871 TI - Efficient Access to Multifunctional Trifluoromethyl Alcohols through Base-Free Catalytic Asymmetric C-C Bond Formation with Terminal Ynamides. AB - The asymmetric addition of terminal ynamides to trifluoromethyl ketones with a readily available chiral zinc catalyst gives CF3 -substituted tertiary propargylic alcohols in up to 99 % yield and 96 % ee. The exclusion of organozinc additives and base as well as the general synthetic utility of the products are key features of this reaction. The value of the beta-hydroxy-beta-trifluoromethyl ynamides is exemplified by selective transformations to chiral Z- and E-enamides, an amide, and N,O-ketene acetals. The highly regioselective hydration, stereoselective reduction, and hydroacyloxylation reactions proceed with high yields and without erosion of the ee value of the parent beta-hydroxy ynamides. PMID- 26806873 TI - Prefrontal GABA Levels Measured With Magnetic Resonance Spectroscopy in Patients With Psychosis and Unaffected Siblings. AB - OBJECTIVE: The authors sought to compare GABA levels in treated and untreated patients with psychosis with levels in their unaffected siblings and healthy control subjects, and to assess the effects of antipsychotic medications on GABA levels. METHOD: GABA+ levels (i.e., including signal from unrelated proteins or macromolecules) referenced to creatine or water were studied with J-edited proton spectroscopy in the dorsal anterior cingulate cortex of 289 individuals: 184 healthy control subjects, 83 treated patients with psychosis, 25 untreated patients, 31 unaffected siblings, and 17 patients studied both while off all medications and while on a single antipsychotic. RESULTS: GABA+ levels in the dorsal anterior cingulate did not differ between untreated patients and healthy controls. For treated patients, levels were modestly lower for GABA+/creatine but did not differ for GABA+/water compared with healthy controls. For both GABA+ measures, unaffected siblings had significantly lower levels compared with controls. GABA+/creatine showed a modest degree of familiality (intraclass correlation=0.36). Antipsychotic dosage was negatively correlated with GABA+ levels, but the on-off medication studies indicated no difference in GABA+ levels on antipsychotics compared with off antipsychotics. CONCLUSIONS: GABA+/creatine in the dorsal anterior cingulate may constitute an intermediate phenotype with low effect size for psychosis, but GABA+/water measures do not fully support this conclusion. Low GABA+ levels in unaffected siblings could suggest a genetic association, but the failure to find consistent evidence of this phenotype in the patients themselves weakens genetic inference on risk for psychosis. Replication in independent samples of siblings is warranted to confirm the potential genetic risk association. PMID- 26806872 TI - Depression-Related Increases and Decreases in Appetite: Dissociable Patterns of Aberrant Activity in Reward and Interoceptive Neurocircuitry. AB - OBJECTIVE: Appetite and weight changes are common but variable diagnostic markers in major depressive disorder: some depressed individuals manifest increased appetite, while others lose their appetite. Many of the brain regions implicated in appetitive responses to food have also been implicated in depression. It is thus remarkable that there exists no published research comparing the neural responses to food stimuli of depressed patients with increased versus decreased appetites. METHOD: Using functional MRI, brain activity was compared in unmedicated depressed patients with increased or decreased appetite and healthy control subjects while viewing photographs of food and nonfood objects. The authors also measured how resting-state functional connectivity related to subjects' food pleasantness ratings. RESULTS: Within putative reward regions, depressed participants with increased appetites exhibited greater hemodynamic activity to food stimuli than both those reporting appetite decreases and healthy control subjects. In contrast, depressed subjects experiencing appetite loss exhibited hypoactivation within a region of the mid-insula implicated in interoception, with no difference observed in this region between healthy subjects and those with depression-related appetite increases. Mid-insula activity was negatively correlated with food pleasantness ratings of depressed participants with increased appetites, and its functional connectivity to reward circuitry was positively correlated with food pleasantness ratings. CONCLUSIONS: Depression-related increases in appetite are associated with hyperactivation of putative mesocorticolimbic reward circuitry, while depression-related appetite loss is associated with hypoactivation of insular regions that support monitoring the body's physiological state. Importantly, the interactions among these regions also contribute to individual differences in the depression-related appetite changes. PMID- 26806875 TI - Clinical Features and Prognosis of Generalized Lymphatic Anomaly, Kaposiform Lymphangiomatosis, and Gorham-Stout Disease. AB - BACKGROUND: Complex lymphatic anomalies are intractable lymphatic disorders, including generalized lymphatic anomaly (GLA), Gorham-Stout disease (GSD), and kaposiform lymphangiomatosis (KLA). The etiology of these diseases remains unknown and diagnosis is confused by their similar clinical findings. This study aimed to clarify the differences in clinical features and prognosis among GLA, KLA, and GSD, in Japanese patients. PROCEDURE: Clinical features, radiological and pathological findings, treatment, and prognosis of patients were obtained from a questionnaire sent to 39 Japanese hospitals. We divided the patients into three groups according to radiological findings of bone lesions and pathology. Differences in clinical findings and prognosis were analyzed. RESULTS: Eighty five patients were registered: 35 GLA, 9 KLA, and 41 GSD. Disease onset was more common in the first two decades of life (69 cases). In GSD, osteolytic lesions were progressive and consecutive. In GLA and KLA, 18 patients had osteolytic lesions that were multifocal and nonprogressive osteolysis. Thoracic symptoms, splenic involvement, and ascites were more frequent in GLA and KLA than in GSD. Hemorrhagic pericardial and pleural effusions were more frequent in KLA than GLA. GSD had a significantly favorable outcome compared with combined GLA and KLA (P = 0.0005). KLA had a significantly poorer outcome than GLA (P = 0.0268). CONCLUSIONS: This survey revealed the clinical features and prognosis of patients with GLA, KLA, and GSD. Early diagnosis and treatment of KLA are crucial because KLA has high mortality. Further prospective studies to risk-stratify complex lymphatic anomalies and optimize management for KLA are urgently needed. PMID- 26806874 TI - Common and Dissociable Mechanisms of Executive System Dysfunction Across Psychiatric Disorders in Youth. AB - OBJECTIVE: Disruption of executive function is present in many neuropsychiatric disorders. However, determining the specificity of executive dysfunction across these disorders is challenging given high comorbidity of conditions. Here the authors investigate executive system deficits in association with dimensions of psychiatric symptoms in youth using a working memory paradigm. The authors hypothesize that common and dissociable patterns of dysfunction would be present. METHOD: The authors studied 1,129 youths who completed a fractal n-back task during functional magnetic resonance imaging at 3-T as part of the Philadelphia Neurodevelopmental Cohort. Factor scores of clinical psychopathology were calculated using an item-wise confirmatory bifactor model, describing overall psychopathology as well as four orthogonal dimensions of symptoms: anxious-misery (mood and anxiety), behavioral disturbance (attention deficit hyperactivity disorder and conduct disorder), psychosis-spectrum symptoms, and fear (phobias). The effect of psychopathology dimensions on behavioral performance and executive system recruitment (2-back > 0-back) was examined using both multivariate (matrix regression) and mass-univariate (linear regression) analyses. RESULTS: Overall psychopathology was associated with both abnormal multivariate patterns of activation and a failure to activate executive regions within the cingulo opercular control network, including the frontal pole, cingulate cortex, and anterior insula. In addition, psychosis-spectrum symptoms were associated with hypoactivation of the left dorsolateral prefrontal cortex, whereas behavioral symptoms were associated with hypoactivation of the frontoparietal cortex and cerebellum. In contrast, anxious-misery symptoms were associated with widespread hyperactivation of the executive network. CONCLUSIONS: These findings provide novel evidence that common and dissociable deficits within the brain's executive system are present in association with dimensions of psychopathology in youth. PMID- 26806876 TI - Antibiotic consumption in non-teaching Lebanese hospitals: A cross-sectional study. AB - The rising threat of antibiotic resistance is linked to patterns of antibiotic use in hospital settings where global efforts are undertaken to encourage reporting and benchmarking antibiotic consumption in an attempt to improve prescription regimens. In Lebanon, where data concerning the level of antibiotic consumption in hospitals is scarce, the aim of our paper is to track the intensity of antibiotic consumption in order to identify potential evidence of antibiotic misuse or abuse. The study is conducted in 2012 for a period of 12 month using data from pharmacy records in 27 non-teaching Lebanese hospitals according to the Anatomical, Therapeutic and chemical classification system and Defined Daily Dose (ATC/DDD) recommended by the World Health Organization and compiling data on ABC Calc software version 3.1. Results show that the average antibiotic consumption excluding pediatric cases is 72.56 Defined Daily Dose per 100 Bed-Days (DDD/100BD). Total broad spectrum antibiotic consumption is 12.14 DDD/100BD with no significant difference found between public and private hospitals (p>0.05 for all). The most commonly used antibiotics were Amoxycillin/Clavulanic acid, Ceftriaxone, Amoxycillin and Cefuroxime for parenteral use. Consumption of beta-lactams, Cephalosporins, Carbapenems, Monobactams and quinolones did not vary significantly by region, occupancy rate, number of beds including the number of intensive care unit beds. Our data findings provides baseline information on patterns of antibiotic consumption in Lebanon and the issue calls for concerted efforts to encourage data reporting on national basis and to correlate future findings with results of antibiotic susceptibility testing which can provide insights and tools needed to assess the public health consequences of antimicrobial misuse and to evaluate the impact of antibiotic resistance containment interventions. PMID- 26806878 TI - Mechanisms of current fluctuation in ambipolar black phosphorus field-effect transistors. AB - Multi-layer black phosphorus has emerged as a strong candidate owing to its high carrier mobility with most of the previous research work focused on its p-type properties. Very few studies have been performed on its n-type electronic characteristics which are important not only for the complementary operation for logic, but also crucial for understanding the carrier transport through the metal black phosphorus junction. A thorough understanding and proper evaluation of the performance potential of both p- and n-types are highly desirable. In this paper, we investigate the temperature dependent ambipolar operation of both electron and hole transport from 300 K to 20 K. On-currents as high as 85 MUA MUm(-1) for a 0.2 MUm channel length BP nFET at 300 K are observed. Moreover, we provide the first systematic study on the low frequency noise mechanisms for both n-channel and p-channel BP transistors. The dominated noise mechanisms of the multi-layer BP nFET and pFET are mobility fluctuation and carrier number fluctuations with correlated mobility fluctuations, respectively. We have also established a baseline of the low electrical noise of 8.1 * 10(-9)MUm(2) Hz(-1) at 10 Hz at room temperature for BP pFETs, which is 3 times improvement over previous reports, and 7.0 * 10(-8)MUm(2) Hz(-1) for BP nFETs for the first time. PMID- 26806879 TI - Postdialysis Fatigue: A Frequent and Debilitating Symptom. AB - Postdialysis fatigue (PDF) is a frequent and debilitating symptom of patients on chronic hemodialysis that affects their daily living and quality of life. Little is known about the mechanisms underlying this symptom and its severity. Only a few studies have investigated therapeutic interventions and with conflicting results. Given the major impact of PDF on the quality of life of hemodialysis patients, a larger effort is warranted to better understand, prevent, and treat PDF. PMID- 26806881 TI - Relb acts downstream of medullary thymic epithelial stem cells and is essential for the emergence of RANK(+) medullary epithelial progenitors. AB - Thymic epithelial cells (TECs) provide essential signals for alphabetaT-cell development, and medullary TECs (mTECs) control T-cell tolerance through both negative selection and Foxp3(+) regulatory T (Treg) cell development. Although heterogeneity within the mTEC compartment is well studied, the molecular regulators of specific stages of mTEC development are still poorly understood. Given the importance of the RANK-RANKL axis in thymus medulla formation, we have used RANK Venus reporter mice to analyze the ontogeny of RANK(+) TECs during development and correlated RANK expression with mTEC stem cells defined by SSEA 1. In addition, we have investigated how requirements for the key regulators Foxn1 and Relb map to specific stages of mTEC development. Here, we show SSEA 1(+) mTEC stem cells emerge prior to RANK expression and are present in both nude and Relb(-/-) mice, providing direct evidence that mTEC lineage specification occurs independently of Foxn1 and Relb. In contrast, we show that Relb is necessary for the effective production of downstream RANK(+) mTEC progenitors. Collectively, our work defines stage-specific requirements for critical TEC regulators during medulla development, including the timing of Relb dependency, and provides new information on mechanisms controlling mTEC specification. PMID- 26806882 TI - Panniculitis as the first sign of haemophagocytic lymphohistiocytosis in a 12 year-old boy. PMID- 26806883 TI - Molecular Order of Arterial Collagen Using Circular Polarization Second-Harmonic Generation Imaging. AB - Second-harmonic generation (SHG) originates from the interaction between upconverted fields from individual scatterers. This renders SHG microscopy highly sensitive to molecular distribution. Here, we aim to take advantage of the difference in SHG between aligned and partially aligned molecules to probe the degree of molecular order during biomechanical testing, independently of the absolute orientation of the scattering molecules. Toward this goal, we implemented a circular polarization SHG imaging approach and used it to quantify the intensity change associated with collagen fibers straightening in the arterial wall during mechanical stretching. We were able to observe the delayed alignment of collagen fibers during mechanical loading, thus demonstrating a simple method to characterize molecular distribution using intensity information alone. PMID- 26806884 TI - Biothermal sensing of a torsional artificial muscle. AB - Biomolecule responsive materials have been studied intensively for use in biomedical applications as smart systems because of their unique property of responding to specific biomolecules under mild conditions. However, these materials have some challenging drawbacks that limit further practical application, including their speed of response and mechanical properties, because most are based on hydrogels. Here, we present a fast, mechanically robust biscrolled twist-spun carbon nanotube yarn as a torsional artificial muscle through entrapping an enzyme linked to a thermally sensitive hydrogel, poly(N isopropylacrylamide), utilizing the exothermic catalytic reaction of the enzyme. The induced rotation reached an equilibrated angle in less than 2 min under mild temperature conditions (25-37 degrees C) while maintaining the mechanical properties originating from the carbon nanotubes. This biothermal sensing of a torsional artificial muscle offers a versatile platform for the recognition of various types of biomolecules by replacing the enzyme, because an exothermic reaction is a general property accompanying a biochemical transformation. PMID- 26806914 TI - Carbon and nitrogen additions induce distinct priming effects along an organic matter decay continuum. AB - Decomposition of organic matter (OM) in soil, affecting carbon (C) cycling and climate feedbacks, depends on microbial activities driven by C and nitrogen (N) availability. However, it remains unknown how decomposition of various OMs vary across global supplies and ratios of C and N inputs. We examined OM decomposition by incubating four types of OM (leaf litter, wood, organic matter from organic and mineral horizons) from a decay continuum in a subtropical forest at Ailao Mountain, China with labile C and N additions. Decomposition of wood with high C:N decreased for 3.9 to 29% with these additions, while leaf decomposition was accelerated only within a narrow C:N range of added C and N. Decomposition of OM from organic horizon was accelerated by high C:N and suppressed by low C:N, but mineral soil was almost entirely controlled by high C:N. These divergent responses to C and N inputs show that mechanisms for priming (i.e. acceleration or retardation of OM decomposition by labile inputs) vary along this decay continuum. We conclude that besides C:N ratios of OM, those of labile inputs control the OM decay in the litter horizons, while energy (labile C) regulates decomposition in mineral soil. This suggests that OM decomposition can be predicted from its intrinsic C:N ratios and those of labile inputs. PMID- 26806916 TI - Effect of Component Mobility on the Properties of Macromolecular [2]Rotaxanes. AB - Macromolecular [2]rotaxanes comprising a polymer axle and crown ether wheel were synthesized to evaluate the effect of component mobility on the properties of the axle polymer, especially its crystallinity. Living ring-opening polymerization of delta-valerolactone with a pseudorotaxane initiator with a hydroxy group at the axle terminus was followed by end-capping with a bulky isocyanate. This yielded macromolecular [2]rotaxanes (M2Rs) possessing polyester axles of varying molecular weights. The crystallinity of the axle polymers of two series of M2Rs, with either fixed and movable components, was evaluated by differential scanning calorimetry. The results revealed that the effect of component mobility was significant in the fixed and movable M2Rs with a certain axle length, thus suggesting that the properties of the axle polymer depend on the mobility of the polyrotaxane components. PMID- 26806917 TI - Two-Dimensional Speckle Tracking Echocardiography in Heart Transplant Patients: Two-Year Follow-Up of Right and Left Ventricular Function. AB - BACKGROUND: Evolution of left and right ventricular (LV and RV) function after heart transplantation (HT) has not been well described. Our objective was to evaluate the evolution of echocardiographic parameters of both ventricles along the first 2 years after HT. METHODS: We followed 31 HT recipients with serial echocardiograms for up to 2 years. Echocardiograms with AR >=2R were excluded. We analyzed LV global longitudinal strain (LV GLS) by speckle tracking in 12 segments in four- and two-chamber views and RV global longitudinal strain (RV GLS) in four-chamber view. Control group included 25 healthy volunteers. RESULTS: Even though LVEF was preserved, LV GLS was reduced early post-HT (-17.7 +/- 3.0 in HT vs. -20.7 +/- 2.8 in controls, P = 0.02), improving progressively until its complete normalization 2 years after HT (-20.0 +/- 3.7 vs. -20.7 +/- 2.8, P = 0.60). TAPSE was impaired in the early post-HT period and increased progressively (11.9 +/- 2.9 mm at baseline vs. 19.0 +/- 3.6 mm at 2 years, P < 0.001). RV GLS rose during follow-up as well (-17.4 +/- 3.5 at baseline vs. -22.6 +/- 3.3 at 2 years, P = 0.001), reaching normal values 1 year after HT. CONCLUSION: In this series of HT recipients with uneventful postoperative course, LV and RV GLS values were significantly reduced early after HT and improved progressively until their complete normalization two and 1 year after HT, respectively. This is the first study to show a full recovery of LV and RV deformation parameters and offers "normal" strain values that, if confirmed in larger studies, could be useful for monitoring the evolution of HT recipients. PMID- 26806918 TI - Synergistic proinflammatory interactions of microbial toxins and structural components characteristic to moisture-damaged buildings. AB - Indoor exposure to microbes and their structural and metabolic compounds is notoriously complex. To study proinflammatory interactions between the multiple microbial agents, macrophages derived from human THP-1 monocytic cells were exposed to several concentrations of microbial toxins alone (emodin, enniatin B, physcion, sterigmatocystin, valinomycin) and in combination with microbial structural components (bacterial lipopolysaccharide [LPS] or fungal beta-glucan). While the expression of proinflammatory cytokines TNFalpha and IL-1beta to single toxins alone was modest, low-dose co-exposure with structural components increased the responses of emodin, enniatin B, and valinomycin synergistically, both at the mRNA and protein level, as measured by RT-qPCR and ELISA, respectively. Co-exposure of toxins and beta-glucan resulted in consistent synergistically increased expression of several inflammation-related genes, while some of the responses with LPS were also inhibitory. Co-exposure of toxins with either beta-glucan or LPS induced also mitochondrial damage and autophagocytosis. The results demonstrate that microbial toxins together with bacterial and fungal structural components characteristic to moisture-damaged buildings can have drastic synergistic proinflammatory interactions at low exposure levels. PMID- 26806951 TI - Traceless Synthesis of Asymmetrically Modified Bivalent Nucleosomes. AB - Nucleosomes carry extensive post-translational modifications (PTMs), which results in complex modification patterns that are involved in epigenetic signaling. Although two copies of each histone coexist in a nucleosome, they may not carry the same PTMs and are often differently modified (asymmetric). In bivalent domains, a chromatin signature prevalent in embryonic stem cells (ESCs), namely H3 methylated at lysine 4 (H3K4me3), coexists with H3K27me3 in asymmetric nucleosomes. We report a general, modular, and traceless method for producing asymmetrically modified nucleosomes. We further show that in bivalent nucleosomes, H3K4me3 inhibits the activity of the H3K27-specific lysine methyltransferase (KMT) polycomb repressive complex 2 (PRC2) solely on the same histone tail, whereas H3K27me3 stimulates PRC2 activity across tails, thereby partially overriding the H3K4me3-mediated repressive effect. To maintain bivalent domains in ESCs, PRC2 activity must thus be locally restricted or reversed. PMID- 26806954 TI - The rise and fall of anaesthesia-related neurotoxicity and the immature developing human brain. PMID- 26806952 TI - Why Are Obstetric Units in Rural Hospitals Closing Their Doors? AB - OBJECTIVES: To understand hospital- and county-level factors for rural obstetric unit closures, using mixed methods. DATA SOURCES: Hospital discharge data from Healthcare Cost and Utilization Project's Statewide Inpatient Databases, American Hospital Association Annual Survey, and Area Resource File for 2010, as well as 2013-2014 telephone interviews of all 306 rural hospitals in nine states with at least 10 births in 2010. Via interview, we ascertained obstetric unit status, reasons for closures, and postclosure community capacity for prenatal care. STUDY DESIGN: Multivariate logistic regression and qualitative analysis were used to identify factors associated with unit closures between 2010 and 2014. PRINCIPAL FINDINGS: Exactly 7.2 percent of rural hospitals in the study closed their obstetric units. These units were smaller in size, more likely to be privately owned, and located in communities with lower family income, fewer obstetricians, and fewer family physicians. Prenatal care was still available in 17 of 19 communities, but local women would need to travel an average of 29 additional miles to access intrapartum care. CONCLUSIONS: Rural obstetric unit closures are more common in smaller hospitals and communities with a limited obstetric workforce. Concerns about continuity of rural maternity care arise for women with local prenatal care but distant intrapartum care. PMID- 26806955 TI - Animal models can help us prevent nerve injuries in regional anaesthesia for patients. PMID- 26806956 TI - The influence of propofol and sevoflurane on intestinal motility during laparoscopic surgery. AB - BACKGROUND: Volatile anaesthetics have an influence on small bowel peristalsis during laparoscopic surgery. A recent study concluded that desflurane increased intestinal motility compared to sevoflurane. Hence, a desflurane-based anaesthesia protocol may reduce surgical exposure during intestinal suturing or stapling due to small bowel hyperperistalsis. The effect of propofol on intestinal motility is not well studied. We tested the hypothesis that a propofol remifentanil anaesthesia increases intestinal contractions in comparison with a sevoflurane-remifentanil anaesthesia. METHODS: Patients scheduled for laparoscopic gastric bypass surgery were randomized in this single blind randomized controlled trial to receive remifentanil combined with sevoflurane or propofol (ISRCTN 12921661). Bispectral index monitoring was used to guide depth of anaesthesia. Visual observation of peristaltic waves was performed during 1 min at the planned site of the jejunostomy. Statistical analysis was performed using Wilcoxon two-sample test. RESULTS: After obtaining written informed consent 50 patients were included. Groups were similar for demographic variables, and depth of anaesthesia during the observations. The median number of peristaltic waves was lower in the sevoflurane-remifentanil group compared to the propofol remifentanil group (0 vs. 6, P < 0.001). CONCLUSION: Propofol-remifentanil increases intestinal motility compared with sevoflurane-remifentanil during laparoscopic gastric bypass surgery. A sevoflurane-based protocol can help to avoid disturbing peristalsis. PMID- 26806957 TI - Impact of a beta-blocker and/or acute hemodilution on cerebral oxygenation during apneic hypoxia. AB - BACKGROUND: beta-blockers reduce the tolerance for acute hemodilution by decreasing cerebral oxygenation and may contribute to the incidence of stroke. We hypothesized that beta-blockers also increase the risk for cerebral hypoxia when apneic hypoxia occurs. METHODS: After induction of isoflurane, 14 swine (mean +/- SD =25.3 +/- 0.8 kg) were studied using 200 MUg/kg/min of landiolol or saline (control group) in three sequential stages: before, during, and after landiolol (saline) infusion. In each stage, after 5 min of mechanical ventilation with 100% oxygen, apnea was induced until the time to < 70% oxygen saturation. Hemodynamic and blood gas variables were measured, and the cerebral tissue oxygenation index (TOI) was recorded by near infrared spectroscopy (apnea experiment). After these steps, hemodilution was induced by hemorrhage of 600 ml and infusion of the same volume of hydroxyethylstarch, and the apnea experiments were then conducted before, during, and after landiolol (saline) infusion similarly to before hemodilution. RESULTS: Landiolol decreased TOI at 1 min after apnea and at SpO2 < 70% by 3.3% and 7.0% from each corresponding value at baseline, and by 13.1% and 20.3% during hemodilution. Landiolol shifted the relationship between TOI and arterial hemoglobin oxygen saturation (SaO2 ) or arterial partial pressure of oxygen (PaO2 ) to the left; and reduced TOI at similar arterial blood oxygenation. This phenomenon was marked during hemodilution. CONCLUSIONS: Landiolol reduces cerebral tissue oxygenation during apneic hypoxia. beta blockers increase the risk for cerebral hypoxia when apneic hypoxia occurs, especially during acute hemodilution. PMID- 26806958 TI - Perioperative aspects of abdominal aortic surgery; focus on choice of anesthetics. PMID- 26806959 TI - There is no cephalocaudal gradient of computed tomography densities or lung behavior in supine patients with acute respiratory distress syndrome. AB - BACKGROUND: There is debate whether pressure transmission within the lungs and alveolar collapse follow a hydrostatic pattern or the compression exerted by the weight of the heart and the diaphragm causes collapse localized in the areas adjacent to these structures. The second hypothesis proposes the existence of a cephalocaudal gradient in alveolar collapse. We aimed to define whether or not lung density and collapse follow a 'liquid-like' pattern with homogeneous isogravitational layers along the cephalocaudal axis in acute respiratory distress syndrome lungs. METHODS: Acute respiratory distress syndrome patients were submitted to full lung computed tomography scans at positive end-expiratory pressure (PEEP) zero (before) and 25 cmH2 O after a maximum-recruitment maneuver. PEEP was then decreased by 2 cmH2 O every 4 min, and a semi-complete scan performed at the end of each PEEP step. RESULTS: Lung densities were homogeneous within each lung layer. Lung density increased along the ventrodorsal axis toward the dorsal region (beta = 0.49, P < 0.001), while there was no increase, but rather a slight decrease, toward the diaphragm along the cephalocaudal axis and toward the heart. Higher PEEP attenuated density gradients. At PEEP 18 cmH2 O, dependent lung regions started to collapse massively, while best compliance was only reached at a lower PEEP. CONCLUSIONS: We could not detect cephalocaudal gradients in lung densities or in alveolar collapse. Likely, external pressures applied on the lung by the chest wall, organs, and effusions are transmitted throughout the lung in a hydrostatic pattern with homogeneous consequences at each isogravitational layer. A single cross-sectional image of the lung could fully represent the heterogeneous mechanical properties of dependent and non dependent lung regions. PMID- 26806960 TI - On the Mechanism of Berberine-INF55 (5-Nitro-2-phenylindole) Hybrid Antibacterials. AB - Berberine-INF55 hybrids are a promising class of antibacterials that combine berberine and the NorA multidrug resistance pump inhibitor INF55 (5-nitro-2 phenylindole) together in one molecule via a chemically stable linkage. Previous studies demonstrated the potential of these compounds for countering efflux mediated antibacterial drug resistance but they didn't establish whether the compounds function as originally intended, i.e. with the berberine moiety providing antibacterial activity and the attached INF55 component independently blocking multidrug resistance pumps, thereby enhancing the activity of berberine by reducing its efflux. We hypothesised that if the proposed mechanism is correct, then hybrids carrying more potent INF55 pump inhibitor structures should show enhanced antibacterial effects relative to those bearing weaker inhibitors. Two INF55 analogues showing graded reductions in NorA inhibitory activity compared with INF55 were identified and their corresponding berberine-INF55 hybrids carrying equivalent INF55 inhibitor structures synthesised. Multiple assays comparing the antibacterial effects of the hybrids and their corresponding berberine-INF55 analogue combinations showed that the three hybrids all show very similar activities, leading us to conclude that the antibacterial mechanism(s) of berberine-INF55 hybrids is different from berberine-INF55 combinations. PMID- 26806961 TI - What's Past is Prologue: Relations Between Early Mathematics Knowledge and High School Achievement. AB - Although previous research has established the association between early-grade mathematics knowledge and later mathematics achievement, few studies have measured mathematical skills prior to school entry, nor have they investigated the predictive power of early gains in mathematics ability. The current paper relates mathematical skills measured at 54 months to adolescent mathematics achievement using multi-site longitudinal data. We find that preschool mathematics ability predicts mathematics achievement through age 15, even after accounting for early reading, cognitive skills, and family and child characteristics. Moreover, we find that growth in mathematical ability between age 54 months and first grade is an even stronger predictor of adolescent mathematics achievement. These results demonstrate the importance of pre kindergarten mathematics knowledge and early math learning for later achievement. PMID- 26806962 TI - Comparison of percutaneous vertebroplasty and percutaneous kyphoplasty for the management of Kummell's disease: A retrospective study. AB - BACKGROUND: Post traumatic osteonecrosis of a vertebral body occurring in a delayed fashion was first described by the German doctor Kummell in 1895. Several studies have reported percutaneous vertebroplasty (PVP), or percutaneous kyphoplasty (PKP) for Kummell's disease achieves good outcomes. However, it is unknown whether a technique is superior for the treatment of this disease. The objective of the study is to compare the efficacy of PVP and PKP for the treatment of Kummell's disease. MATERIALS AND METHODS: A retrospective review was conducted for 73 patients with Kummell's disease. PVP was performed in 38 patients and PKP in 35 patients. Visual analogue score (VAS) was used to evaluate pain. The anterior vertebral height was measured. The operative time, the incidence of cement leakage and the costs were recorded. RESULTS: In both PVP group and PKP group, the VAS and anterior vertebral height significantly improved at 1-day postoperatively (P < 0.05), and the improvement sustained at the final followup (P > 0.05). Between the PVP and PKP groups, there were no significant differences in VAS and the anterior vertebral height at 1-day postoperatively and at the final followup (P > 0.05). The operating time and expense in the PKP group were higher than the PVP group (P < 0.001). Cement leakages in the PKP group were fewer than PVP group (P < 0.05). CONCLUSIONS: PVP is a faster, less expensive option that still provides a comparable pain relief and restoration of vertebral height to PKP for the treatment of Kummell's disease. PKP has a significant advantage over PVP in term of the fewer cement leakages. PMID- 26806963 TI - Morphometric and radiological assessments of dimensions of Axis in dry vertebrae: A study in Indian population. AB - BACKGROUND: The technique of intralaminar screw placement for achieving axis (C2) fixation has been recently described. The purpose of the study was to provide the morphometric and radiological measurements in Indian population and to determine the feasibility of safe translaminar screw placement in this population. To the best of our knowledge there is no study (cadaveric or radiological) done in Indian population to detect suitability of axis bone for laminar screw fixation. MATERIAL AND METHODS: 38 dry axis vertebrae from adult South Indian population were subjected to morphometric measurement and CT scan analysis. Height of posterior arch, midlaminar width(bilateral) in upper 1/3(rd), middle 1/3(rd) and lower 1/3(rd) were measured using high precision Vernier Calipers. Each vertebra was subjected to a spiral CT scan (Philips brilliance 16 slice) thin 0.5 mm slices were taken and reconstruction was done in coronal and sagittal plane. Analysis was done on a CT work station. Using axial slices, sagittal cuts were reconstructed in plane perpendicular to the lamina at the mid laminar point and upper-middle and lower 1/3(rd) width of the lamina measured. Height of the posterior arch was measured in the sagittal plane. Intralaminar angle was measured bilaterally. RESULTS: Middle 1/3(rd) lamina was the thickest portion (mean 5.17 mm +/- 1.42 mm). A total of 32 (84.2%) specimen were having midlaminar width in both lamina greater than 4 mm, however only 27 (71%) out of them had spinous process more than 9 mm. CT scan measurement in middle and lower 1/3(rd) lamina was found to be strongly correlated with the direct measurement. CONCLUSION: There is high variability in the thickness of the C2 lamina. As compared to western population, the axis bones used in the present study had smaller profiles. Hence the safety margin for translaminar screw insertion is low. PMID- 26806964 TI - Degenerated intervertebral disc prolapse and its association of collagen I alpha 1 Spl gene polymorphism: A preliminary case control study of Indian population. AB - BACKGROUND: Degenerated disc disease (DDD) is a common disorder responsible for increased morbidity in a productive age group. Its etiology is multifactorial and genetic factors have been predominantly implicated. Disc prolapse results due to tear in the annulus, which is a fibrous structure composed largely of type I collagen. Functional polymorphism at the Sp1 site of the collagen I alpha 1 (COL1A1) gene has shown a positive association with DDD in Dutch and Greek populations. The purpose of this study was to assess COL1A1 Sp1 gene polymorphism in the Indian population. MATERIALS AND METHODS: Fifty clinically and radiologically proven patients with disc prolapse requiring surgery were included as cases and 50 healthy, age-matched volunteers served as controls. After isolating DNA from their blood sample, genotyping for COL1A1 polymorphism (rs1800012) was performed and identified as GG, GT, and TT. RESULTS: The mean age and body mass index in cases and controls were similar. 76% of the patients were males. The most common site of disc degeneration was L4-L5 (36%), followed by L5 S1 (34%). Homozygous-GG, heterozygous GT, and homozygous TT genotypes were seen in 38 (76%), 10 (20%) and 2 (4%) cases respectively, controls had similar percentage of genotypes as well. The alleles in cases and the control group showed no significant difference (P = 0.6744) and followed the Hardy-Weinberg Equilibrium in the study population. CONCLUSION: The COL1A1 (rs1800012) is in Hardy-Weinberg equilibrium in the present subset of Indian population. But taken as a single factor, it was not found to be associated with DDD in this preliminary study. Disc degeneration is multifactorial and also anticipated to be a result of multiple genes involvement and gene-gene interaction. PMID- 26806965 TI - Return to sporting activity after Birmingham hip resurfacing arthroplasty: Mid term results. AB - BACKGROUND: Hip resurfacing arthroplasty (HRA) is primarily indicated for young, active patients with disabling coxarthrosis who wish to remain active and return to sports after surgery. Relatively few prospective studies have assessed return to sporting activity and impact of gender and age on this. MATERIALS AND METHODS: Seventy-nine consecutive patients treated with HRA were included. Patients were reviewed clinically and radiologically. Function was assessed using the modified University of California Los Angeles (UCLA) activity score. The Oxford, Harris and WOMAC hip scores were calculated. RESULTS: Average age at the time of surgery was 54.9 years (range 34.5-73.6 years). Average preoperative and postoperative UCLA scores were 4 and 7.6 respectively. Patients were involved in 2 (0-4) sporting activities preoperatively and 2 (0-5) postoperatively. Preoperative and postoperative Oxford Hip Scores, Harris Hip Score and WOMAC scores were 40, 46 and 51 and 16, 94 and 3 respectively (P < 0.0001). Patients returned to sports at an average of 3 months postoperatively. CONCLUSION: Patients were able to return to sports by 3 months and perform the same number of activities at preoperative intensity. Activity levels are maintained up to the medium term with few complications. PMID- 26806966 TI - Calcar femorale grafting in the hemiarthroplasty of the hip for unstable inter trochanteric fractures. AB - BACKGROUND: The sliding screw-plate devices and cephalo-medullary nail devices have performed well in stable inter-trochanteric fractures in patients with reasonably good quality of bone. However, their suboptimal performance in comminuted fractures in the presence of osteoporotic bone has prompted many surgeons to consider bipolar hemiarthroplasty as the primary modality of management of comminuted inter-trochanteric fractures in elderly patients. However, long term stability of the hemiarthroplasty implant also may be compromised due to the presence of postero-medial bone loss at the area of the calcar. MATERIALS AND METHODS: We have presented a simple and effective technique of calcar grafting by harvesting cortical bone strut from the neck of the fractured femur. A total of 34 patients with inter-trochanteric fractures of the femur were treated with calcar grafting. The mean age was 79.2 years. The graft was harvested from the calcar region of the head and neck fragment of the femur and wedged between the medial femoral cortex and medial edge of the prosthesis. The mean followup period was 54.5 months. RESULTS: In 32 of 34 (94%) patients in our series, the calcar graft healed well without dislodgement. There was graft resorption in two patients associated with subsidence of the implant and loosening. CONCLUSION: Calcar grafting using this technique provides stability to the implant in the presence of comminution and incorporates well in the majority of patients. Donor site morbidity of graft harvesting is also avoided. PMID- 26806967 TI - The reliability of ultrasonography in developmental dysplasia of the hip: How reliable is it in different hands? AB - BACKGROUND: Developmental dysplasia of the hip (DDH) is the most common skeletal dysplasia. Two principal methods used in early diagnosis of DDH are clinical examination and ultrasonographic investigation. Dogruel et al. found a low specificity of clinical examination in patients with DDH. Additionally, Kamath et al. stated that ultrasonography performed by a radiologist in routine clinical practice is more reliable than physical examination performed by the average clinician. In clinical practice, the application and assessment of hip ultrasonography are completed by a single person. This assessment determines the followup of the patient. Thus, hip ultrasonography performed on the same person by different individuals under the same conditions will yield a more accurate assessment of the reliability of ultrasonographic assessment of DDH. Although inter-observer reliability was high in many previous studies of ultrasound image evaluation, reliability rates vary among studies of the application of ultrasonography. MATERIALS AND METHODS: Inter-examiner reliability of hip ultrasonography was analyzed among four investigators who separately evaluated 100 hips (50 infants). The obtained bone structure angles alpha, cartilage structure angles beta, and distribution of hip types were compared among the investigators. All infants were brought to the hospital for a healthy child followup examination, according to the country's health policy. Babies between 0 and 6 months were included in the study. Babies with any neuromuscular disorders, neural tube defects or any type of genetic anomalies were excluded from the study. The study was explained to the families of all infants and written informed consent was obtained. RESULTS: There was a significant difference in the hip type determined by the investigators with respect to alpha and beta angles (P < 0.01, P < 0.01, P = 0.002). The average alpha measurements of the first orthopedist, second orthopedist, first radiologist, and second radiologist were 67.38 +/- 6.24, 65.60 +/- 5.84, 65.44 +/- 4.59, and 62.59 +/- 4.50, respectively. The average beta measurements of the first orthopedist, second orthopedist, first radiologist, and second radiologist were 53.85 +/- 8.86, 50.74 +/- 7.80, 44.77 +/ 6.30, and 44.39 +/- 5.81, respectively. Agreement among the results obtained by the clinicians was investigated in dual comparisons. The relative agreement according to the alpha angle ranged from 3.6% to 44.5%, and the relative concordance according to the beta angle ranged from 0.9% to 45.3%. Agreement regarding hip typing was determined to range from 19.1% to 42.6%. CONCLUSION: Sonographic evaluation of the hip appears to vary depending on the investigator. PMID- 26806968 TI - Patellar tendon or hamstring graft anterior cruciate ligament reconstructions in patients aged above 50 years. AB - BACKGROUND: The treatment of anterior cruciate ligament (ACL) injury consists of arthroscopic ACL reconstruction with patellar tendon or hamstring graft. Satisfactory results have been reported so far in the younger age group. Dilemma arises regarding the suitability of ACL reconstruction in patients aged 50 years and above. This retrospective analyses the outcome of ACL reconstruction in patients aged 50 years and above. MATERIALS AND METHODS: 55 patients aged 50 years and above presented to our institution with symptomatic ACL tear and were managed with arthroscopic reconstruction with patellar tendon/hamstring graft. 22 patients underwent ACL reconstruction with bone- patellar tendon-bone graft and the remaining 33 with a hamstring graft. Evaluation of functional outcome was performed using International Knee Documentation Committee (IKDC) and Lysholm scoring in the preoperative period, at the end of 1 year and at the final followup. Radiographic evaluation was performed using the Kellgren-Lawrence grading system. RESULTS: The mean preoperative IKDC score was 39.7 +/- 3.3. At the end of 1-year following the operation, the mean IKDC score was 73.6 +/- 4.9 and at the final followup was 67.8 +/- 7.7. The mean preoperative Lysholm score was 40.4 +/- 10.3. At the end of 1-year following the intervention, the mean Lysholm score was 89.7 +/- 2.1 and at final followup was 85.3 +/- 2.5. Overall, 14 out of 42 patients who underwent radiographic assessment showed progression of osteoarthritis changes at the final followup after the intervention. CONCLUSION: In our study, there was a statistically significant improvement in the IKDC and Lysholm scores following the intervention. There was a slight deterioration in the scores at the final followup but the overall rate of satisfaction was still high and most of the patients were able to do their routine chores and light exercises suitable for their age group. Around one-third of patients show progression of radiographic changes in the postoperative period and this requires long term evaluation. PMID- 26806969 TI - Outcome of angular stable locking plate fixation of tibial plateau fractures Midterm results in 101 patients. AB - BACKGROUND: Articular reconstruction and stable fixation of tibial plateau fractures and its various subtypes continue to represent a surgical challenge. Only few trials have studied results following angular stable plate fixation. The present study aimed to investigate the clinical, radiological, functional and quality of life results following tibial plateau fractures using angular stable plate fixation. MATERIALS AND METHODS: 101 patients were retrospectively studied using functional (ROM; KSS; VAS), radiographic (osteoarthritis score, loss of reduction) and quality of life (WOMAC; Lysholm) scores. There were 46 males and 55 females. The average of patients was 51 years (range 22-77 years). Study groups were assigned according to the AO fracture classification. RESULTS: Mean followup was 57 +/- 30 months. Fracture type distribution revealed a significantly (P < 0.001) increased number of type B- (62.4%) compared to C fractures. Functional assessment showed a significantly better total KSS (84.1 +/ 15.6 vs. 74.7 +/- 18.0; P = 0.01) as well as ROM (active: 124 degrees +/-17 degrees vs. 116 degrees +/-15 degrees , P = 0.014; passive: 126 degrees +/-18 degrees vs. 118 +/- 14 degrees , P = 0.017) in the B-fracture group. VAS was found to be markedly higher (P = 0.0039) following type C-fractures. Rating osteoarthritis secondary to a tibial plateau fracture as a function of injury severity (r = 0.485; P < 0.001) and relating the loss of reduction to the grade of evolving osteoarthritis (r = 0.643; P < 0.001) a positive correlation was found. Quality of life showed significantly improved results for Lysholm score (P = 0.004) following B-fractures with low overall values for the WOMAC score. CONCLUSION: Presented data provide sufficient evidence that anatomic restoration of tibial plateau fractures with angular stable plate fixation result in decreased loss of reduction and declined incidence of posttraumatic osteoarthritis, thereby providing acceptable mid to long term outcome. PMID- 26806970 TI - Dynamic medial patellofemoral ligament reconstruction in recurrent patellar instability: A surgical technique. AB - The medial patellofemoral ligament (MPFL) is the primary stabilizer of the patellofemoral joint; its reconstruction has been recommended in adults over the past decade after recurrent patellar instability. However, there has been no standardized technique for reconstruction, therefore, ideal graft and technique for reconstruction are yet undetermined. However, dynamic MPFL reconstruction studies claim to be superior to other procedures as it is more anatomical. This preliminary study aims at assessing the outcomes of MPFL reconstruction in a dynamic pattern using hamstring graft. We performed this procedure in four consecutive patients with chronic patellar instability following trauma. MPFL reconstruction was done with hamstring tendons detached distally and secured to patellar periosteum after being passed through a bony tunnel in the patella without an implant and using the medial collateral ligament as a pulley. In all 4 knees, the MPFL reconstruction was isolated and was not associated with any other realignment procedures. No recurrent episodes of dislocation or subluxation were reported at 24 months followup. PMID- 26806971 TI - Augmentation of bone healing in delayed and atrophic nonunion of fractures of long bones by partially decalcified bone allograft (decal bone). AB - BACKGROUND: Autograft from iliac crest is considered as gold standard for augmentation of bone healing in delayed and nonunion of fractures. Bone demineralized with 0.6N hydrochloric acid has shown to retain its osteoinductive capacity. We report the outcome of partially decalcified bone allograft (decal bone) in the treatment of delayed union and atrophic nonunions of bones. MATERIALS AND METHODS: Twenty patients with clinicoradiological diagnosis of delayed union or atrophic nonunion of long bone fractures were included in this retrospective study. Patients at extreme of ages (<18 years and >60 years), pathological fractures, metabolic bone diseases, infected nonunion, hypertrophic nonunion and those having systemic illness like diabetes mellitus and on drugs that impair fracture healing were excluded from the study. Decal bone was prepared in the bone bank and maintained in department of orthopedics. Allografting was done in 20 patients of delayed union (9/20) and atrophic nonunion (11/20) of long bone fractures with mean age of 34 years (range 18-55 years). The bones involved were humerus (8/20), tibia (7/20) and femur (5/20). Fourteen patients underwent treatment in the form of internal fixation and allografting and six patients were operated with osteoperiosteal allografting. RESULTS: Nineteen patients achieved union in mean time of 14.9 weeks range (range 8-20 weeks). Eight patients had serous discharge from the operative site that subsided in 11 days (range 4-21 days). One patient had pus discharge that required repeat debridement and antibiotics for 6 weeks. The fracture healed in 16 weeks. CONCLUSION: The partially decalcified bone allograft is an effective modality for augmentation of bone healing without complication associated with autograft like donor site morbidity, increased blood loss and increase in the surgical time. PMID- 26806972 TI - Management of segmental skeletal defects by the induced membrane technique. AB - BACKGROUND: Surgical reconstruction of segmental skeletal defects represents a true challenge for the orthopedic surgeons. Recently, Masquelet et al. described a two-stage technique for reconstruction of bone defects, known as the induced membrane technique. The aim of this study is to assess the results of the induced membrane technique in the management of segmental skeletal defects resulting from debridement of bone infection. MATERIALS AND METHODS: Seventeen patients with segmental skeletal defects were treated in our institution by the induced membrane technique. The average age of the patients was 43 years (range 26- 58 years). The causes of the defects were infected gap nonunion in 12 cases and debridement of osteomyelitis in 5 cases. The defects were located in the tibia (n = 13) and the femur (n = 4). The mean defect was 7 cm (range 4 cm - 11 cm). All cases were treated by the induced membrane technique in two-stages. RESULTS: Bone union happened in 14 patients. The limb length discrepancy did not exceed 2.5 cm in the healed cases. The mean time of healing was 10 months (range 6-19 months). The complications included nonunion of the graft in five cases, failure of graft maturation in two cases, reactivation of infection in two cases and refracture after removal of the frame in one case. These complications were managed during the course of treatment and they did not affect the final outcome in all patients except three. CONCLUSION: The induced membrane technique is a valid option for the management of segmental skeletal defects. It is a simple and straight forward procedure, but the time required for growth and maturation of the graft is relatively long. PMID- 26806973 TI - Hydroxyapatite crystals as a bone graft substitute in benign lytic lesions of bone. AB - BACKGROUND: Bone grafts are required to fill a cavity created after curettage of benign lytic lesions of the bone. To avoid the problems associated at donor site with autologous bone graft, we require allograft or bone graft substitutes. We evaluated the healing of lytic lesions after hydroxyapatite (HA) grafting by serial radiographs. MATERIALS AND METHODS: Forty cases of benign lytic lesions of bone were managed by simple curettage and grafting using HA blocks. Commercially available HA of bovine origin (Surgiwear Ltd., Shahjahanpur, India) was used for this purpose. Mean duration of followup was 34.8 months (range 12-84 months). Mean patient age was 19.05 years (range 3-55 years). Radiological staging of graft incorporation was done as per criteria of Irwin et al. 2001. RESULTS: In our series, two cases were in stage I. A total of 11 cases were in stage II and 27 were in stage III. Graft incorporation was radiologically complete by 15 months. Clinical recovery was observed before radiological healing. The average time taken to return to preoperative function was 3 months. Recurrence was observed in giant cell tumor (n = 3) and chondromyxoid fibroma (n = 1). There was no incidence of graft rejection, collapse, growth plate disturbances or antigenic response. CONCLUSIONS: We conclude that calcium HA is biologically acceptable bone graft substitute in the management of benign lytic lesions of bone. PMID- 26806974 TI - Reliability of the mangled extremity severity score in combat-related upper and lower extremity injuries. AB - BACKGROUND: Decision of limb salvage or amputation is generally aided with several trauma scoring systems such as the mangled extremity severity score (MESS). However, the reliability of the injury scores in the settling of open fractures due to explosives and missiles is challenging. Mortality and morbidity of the extremity trauma due to firearms are generally associated with time delay in revascularization, injury mechanism, anatomy of the injured site, associated injuries, age and the environmental circumstance. The purpose of the retrospective study was to evaluate the extent of extremity injuries due to ballistic missiles and to detect the reliability of mangled extremity severity score (MESS) in both upper and lower extremities. MATERIALS AND METHODS: Between 2004 and 2014, 139 Gustillo Anderson Type III open fractures of both the upper and lower extremities were enrolled in the study. Data for patient age, fire arm type, transporting time from the field to the hospital (and the method), injury severity scores, MESS scores, fracture types, amputation levels, bone fixation methods and postoperative infections and complications retrieved from the two level-2 trauma center's data base. Sensitivity, specificity, positive and negative predictive values of the MESS were calculated to detect the ability in deciding amputation in the mangled limb. RESULTS: Amputation was performed in 39 extremities and limb salvage attempted in 100 extremities. The mean followup time was 14.6 months (range 6-32 months). In the amputated group, the mean MESS scores for upper and lower extremity were 8.8 (range 6-11) and 9.24 (range 6-11), respectively. In the limb salvage group, the mean MESS scores for upper and lower extremities were 5.29 (range 4-7) and 5.19 (range 3-8), respectively. Sensitivity of MESS in upper and lower extremities were calculated as 80% and 79.4% and positive predictive values detected as 55.55% and 83.3%, respectively. Specificity of MESS score for upper and lower extremities was 84% and 86.6%; negative predictive values were calculated as 95.45% and 90.2%, respectively. CONCLUSION: MESS is not predictive in combat related extremity injuries especially if between a score of 6-8. Limb ischemia and presence or absence of shock can be used in initial decision-making for amputation. PMID- 26806975 TI - Publication trend in the Indian Journal of Orthopaedics: What is published and why? AB - BACKGROUND: Factors influencing publication of manuscripts in reputed journals have never been studied to the best of our knowledge. This study was conducted to evaluate the trend in publication within the Indian Journal of Orthopaedics (IJO). MATERIALS AND METHODS: A cross-sectional study was conducted by accessing the online database of the IJO. All the issues available online were included. Published articles were classified into one of the following thirteen categories: (i) Basic Sciences (ii) trauma (upper limb and lower limb) (iii) infections (iv) pediatric orthopedics (v) arthroplasty (vi) arthroscopy (vii) spine surgery (viii) musculoskeletal oncology (ix) hand and microvascular surgery (x) adult reconstruction (including the Ilizarov technique) (xi) general orthopedics and miscellaneous (xii) letter to editor (xiii) book review. A scatter diagram was plotted to study the individual trends. RESULTS: A total of 2213 articles from 110 issues published between 1967 and 2014 were studied. Total number of articles per issue have increased over the years. Publications in the fields of trauma, adult reconstruction, arthroscopy and hand and microvascular surgery have increased steadily. Arthroplasty and spine surgery have recorded dramatic increase in publication. On the other hand, publications in the rest of the fields have declined of which the greatest fall is noted in the field of musculoskeletal oncology. CONCLUSIONS: Trend in publication with the IJO has changed over years with more articles being published in arthroplasty and Spine surgery. Despite advances, publication in the field of musculoskeletal oncology has fallen. PMID- 26806976 TI - The chondroprotective effects of intraarticular application of statin in osteoarthritis: An experimental study. AB - BACKGROUND: Osteoarthritis (OA) is the most frequent chronic joint disease causing pain and disability. Recent reports have shown that statin may have the potential to inhibit osteoarthritis. This study of early stage OA developed in an experimental rabbit model, aimed to evaluate the chondroprotective effects of intraarticularly applied atorvastatin on cartilage tissue macroscopically and histopathologically by examining intracellular and extracellular changes by light and electron microscope. MATERIALS AND METHODS: The experimental knee OA model was created by cutting the anterior cruciate ligament of the 20 mature New Zealand rabbits. The rabbits were randomly allocated into two groups of 10. STUDY GROUP: The group that received intraarticular statin therapy; CONTROL GROUP: The group that did not receive any intraarticular statin therapy. The control group received an intraarticular administration of saline and the study group atorvastatin from the 1(st) week postoperatively, once a week for 3 weeks. The knee joints were removed including the femoral and tibial joint surfaces for light and electron microscopic studies of articular cartilages. RESULTS: The mean total points obtained from the evaluation of the lesions that developed in the medial femoral condyle were 11.33 +/- 0.667 for the control group and 1.5 +/- 0.687 for the study group. The mean total points obtained from the evaluation of the lesions that developed in medial tibial plateau cartilage tissue were 11.56 +/- 0.709 for the control group and 1.40 +/- 0.618 for the study group. Electron microscopic evaluation revealed healthy cartilage tissue with appropriate chondrocyte and matrix structure in study group and impaired cartilage tissue in control group. CONCLUSION: Chondroprotective effect of statin on cartilage tissue was determined in this experimental OA model evaluated macroscopically and by light and electron microscope. There are some evidences to believe that the chondroprotective effect of the statin is that, by protecting the structure of the endoplasmic reticulum and the Golgi complex. PMID- 26806977 TI - Transradicular lumbar disc herniation: An extreme variant of intraradicular disc herniation. AB - Intradural or intraradicular lumbar disc herniation (IDH) is a relatively rare condition often diagnosed intraoperatively. We encountered an extreme variant of IDH - a transradicular herniation as the disc material extruded through the lumbar nerve root through a split essentially transecting the nerve root. While failure to recognize intradural and intraradicular disc herniation can lead to failed back surgery, the variant described in the present case could lead to iatrogenic injury and complication if not recognized. A unique case of transradicular lumbar disc herniation in a 25-year-old patient is presented with the depiction of intraoperative images supplementing the text. PMID- 26806978 TI - Isolated dorsal dislocation of the tarsal naviculum. AB - Isolated dislocation of the tarsal naviculum is an unusual injury, scarcely reported in the literature. The naviculum is surrounded by the rigid bony and ligamentous support hence fracture dislocation is more common than isolated dislocation. The mechanism and treatment options remain unclear. In this case report, we describe a 31 year old man who sustained an isolated dorsal dislocation of the left tarsal naviculum, without fracture, when he was involved in a motor vehicle collision. The reported mechanism of the dislocation is a hyper plantar flexion force applied to the midfoot, resulting in a transient disruption of the ligamentous support of the naviculum bone, with dorsal displacement of the bone. The patient was treated with open reduction and Krischner-wire fixation of the navicular after the failure of closed reduction. The wires were removed after 6 weeks postoperatively. Physiotherapy for stiffness and midfoot pain was recommended for 2 months. At 6 months postoperatively, limping, midfoot pain and weakness were reported, no X-ray abnormalities were found. The patient returned to his obvious activities with a normal range of motion. PMID- 26806979 TI - Management of implant-stable distal femoral periprosthetic fractures by distal femoral locking plate: A retrospective study. PMID- 26806980 TI - Author's reply. PMID- 26806981 TI - Erratum: Obituary - Prof T K Shanmugasundaram (1929 - 2008). AB - [This corrects the article on p. 484 in vol. 42.]. PMID- 26806982 TI - Application of ATP-based bioluminescence for bioaerosol quantification: effect of sampling method. AB - An adenosine triphosphate (ATP)-based bioluminescence has potential to offer a quick and affordable method for quantifying bioaerosol samples. Here we report on our investigation into how different bioaerosol aerosolization parameters and sampling methods affect bioluminescence output per bacterium, and implications of that effect for bioaerosol research. Bacillus atrophaeus and Pseudomonas fluorescens bacteria were aerosolized by using a Collison nebulizer (BGI Inc., Waltham, MA) with a glass or polycarbonate jar and then collected for 15 and 60 min with: (1) Button Aerosol Sampler (SKC Inc., Eighty Four, PA) with polycarbonate, PTFE, and cellulose nitrate filters, (2) BioSampler (SKC Inc.) with 5 and 20 mL of collection liquid, and (3) our newly developed Electrostatic Precipitator with Superhydrophobic Surface (EPSS). For all aerosolization and sampling parameters we compared the ATP bioluminescence output per bacterium relative to that before aerosolization and sampling. In addition, we also determined the ATP reagent storage and preparation conditions that that do not affect the bioluminescence signal intensity. Our results show that aerosolization by a Collison nebulizer with a polycarbonate jar yields higher bioluminescence output per bacterium compared to the glass jar. Interestingly enough, the bioluminescence output by P. fluorescens increased substantially after its aerosolization compared to the fresh liquid suspension. For both test microorganisms, the bioluminescence intensity per bacterium after sampling was significantly lower than that before sampling suggesting negative effect of sampling stress on bioluminescence output. The decrease in bioluminescence intensity was more pronounces for longer sampling times and significantly and substantially depended on the sampling method. Among the investigated method, the EPSS was the least injurious for both microorganisms and sampling times. While the ATP-based bioluminescence offers a quick bioaerosol sample analysis method, this works demonstrates that the method output depends on bioaerosol generation and sampling methods, as well as reagent storage. PMID- 26806983 TI - Closing the Communal Gap: The Importance of Communal Affordances in Science Career Motivation. AB - To remain competitive in the global economy, the United States (and other countries) is trying to broaden participation in science, technology, engineering, and mathematics (STEM) by graduating an additional 1 million people in STEM fields by 2018. Although communion (working with, helping, and caring for others) is a basic human need, STEM careers are often (mis)perceived as being uncommunal. Across three naturalistic studies we found greater support for the communal affordance hypothesis, that perceiving STEM careers as affording greater communion is associated with greater STEM career interest, than two alternative hypotheses derived from goal congruity theory. Importantly, these findings held regardless of major (Study 1), college enrollment (Study 2), and gender (Studies 1-3). For undergraduate research assistants, mid-semester beliefs that STEM affords communion predicted end of the semester STEM motivation (Study 3). Our data highlight the importance of educational and workplace motivational interventions targeting communal affordances beliefs about STEM. PMID- 26806984 TI - Iron-Catalyzed Diastereoselective Intramolecular Olefin Aminobromination with Bromide Ion. AB - A new iron-catalyzed diastereoselective aminobromination method is reported for both internal and terminal olefins (yield up to 90% and dr up to >20:1). In this transformation, a functionalized hydroxylamine and bromide ion were used as the nitrogen and bromine source, respectively. This method is compatible with a broad range of olefins and provides a convenient approach to synthetically valuable vicinal bromo primary amines. Our studies suggest that both the diastereoselectivity and enantioselectivity for the olefin aminobromination can be controlled by iron catalysts. PMID- 26806985 TI - Mercury in marine fish, mammals, seabirds, and human hair in the coastal zone of the southern Baltic. AB - Mercury (Hg), aside from having high toxicity, is characterized by its ability to biomagnify in the marine trophic chain. This is an important problem especially in estuaries, or in the coastal zone, particularly near the mouths of large rivers. This study was conducted in the years 2001-2011, in the coastal zone of the Baltic Sea near to the mouth of the River Vistula, which is the second biggest river discharging into the Baltic. Mercury concentration was measured in the tissues and organs of cod, flounder, herring, seals (living in the wild and in captivity), great black-backed gulls, and African penguins from Gdansk Zoo, and also in human hair. Penguins and seals at the seal sanctuary in Hel were fed only herring. In marine birds and mammals and in the pelagic herring, the highest Hg concentration was observed in the kidney and in the liver, while in cod and flounder (located on a higher trophic level) the muscles were the most contaminated with mercury. In gray seals living in the seal sanctuary, Hg concentration in all analyzed tissues and organs except the kidneys was lower in comparison with seals living in the wild. The comparatively small share of fish in the diet of local Polish people and their preference towards the consumption of herring contributed to low concentration of Hg in their hair. The protective mechanisms related to detoxification and elimination of mercury were shown to be more effective in the seals than in the penguins, despite the former consuming around 10 times more food per day. PMID- 26806986 TI - ESTIMATION OF FUNCTIONALS OF SPARSE COVARIANCE MATRICES. AB - High-dimensional statistical tests often ignore correlations to gain simplicity and stability leading to null distributions that depend on functionals of correlation matrices such as their Frobenius norm and other l r norms. Motivated by the computation of critical values of such tests, we investigate the difficulty of estimation the functionals of sparse correlation matrices. Specifically, we show that simple plug-in procedures based on thresholded estimators of correlation matrices are sparsity-adaptive and minimax optimal over a large class of correlation matrices. Akin to previous results on functional estimation, the minimax rates exhibit an elbow phenomenon. Our results are further illustrated in simulated data as well as an empirical study of data arising in financial econometrics. PMID- 26806987 TI - Localized Functional Principal Component Analysis. AB - We propose localized functional principal component analysis (LFPCA), looking for orthogonal basis functions with localized support regions that explain most of the variability of a random process. The LFPCA is formulated as a convex optimization problem through a novel Deflated Fantope Localization method and is implemented through an efficient algorithm to obtain the global optimum. We prove that the proposed LFPCA converges to the original FPCA when the tuning parameters are chosen appropriately. Simulation shows that the proposed LFPCA with tuning parameters chosen by cross validation can almost perfectly recover the true eigenfunctions and significantly improve the estimation accuracy when the eigenfunctions are truly supported on some subdomains. In the scenario that the original eigenfunctions are not localized, the proposed LFPCA also serves as a nice tool in finding orthogonal basis functions that balance between interpretability and the capability of explaining variability of the data. The analyses of a country mortality data reveal interesting features that cannot be found by standard FPCA methods. PMID- 26806988 TI - Codes of Commitment to Crime and Resistance: Determining Social and Cultural Factors over the Behaviors of Italian Mafia Women. AB - This article categorizes thirty-three women in four main Italian Mafia groups and explores social and cultural behaviors of these women. This study introduces the feminist theory of belief and action. The theoretical inquiry investigates the sometimes conflicting behaviors of women when they are subject to systematic oppression. I argue that there is a cultural polarization among the categorized sub-groups. Conservative radicals give their support to the Mafia while defectors and rebels resist the Mafia. After testing the theory, I assert that emancipation of women depends on the strength of their beliefs to perform actions against the Mafiosi culture. PMID- 26806989 TI - Family Resources in Two Generations and School Readiness among Children of Teen Parents. AB - Overall, children born to teen parents experience disadvantaged cognitive achievement at school entry compared to children born to older parents. However, within this population there is variation, with a significant fraction of teen parents' children acquiring adequate preparation for school entry during early childhood. We ask whether the family background of teen parents explains this variation. We use data on children born to teen mothers from three waves of the Early Childhood Longitudinal Study-Birth Cohort (N~700) to study the association of family background with children's standardized reading and mathematics achievement scores at kindergarten entry. When neither maternal grandparent has completed high school, children's scores on standardized assessments of math and reading achievement are one-quarter to one-third of a standard deviation lower compared to families where at least one grandparent finished high school. This association is net of teen mothers' own socioeconomic status in the year prior to children's school entry. PMID- 26806990 TI - Realizing Racial and Ethnic Neighborhood Preferences? Exploring the Mismatches Between What People Want, Where They Search, and Where They Live. AB - The housing search process is an overlooked mechanism in the scholarly research that seeks to understand the causes of persistent racial residential segregation in the United States. Past research has explored in detail the preferences people hold in terms of the racial and ethnic composition of their neighborhoods, and more recently some have also examined the correspondence between racial and ethnic neighborhood preferences and current neighborhood racial/ethnic composition. But an intermediate stage-the racial/ethnic composition of where people search-has not been investigated. We analyze a subsample (n = 382) from the 2004-2005 Chicago Area Study to demonstrate the value of systematically studying the matches-or mismatches-between preferences, search locations, and neighborhood outcomes. We find that for whites, not only their current neighborhoods but also the neighborhoods in which they search for housing have larger percentages of whites than they say they prefer. In contrast, blacks-and to a lesser extent Latinos-search in neighborhoods that correspond to their preferences, but reside in neighborhoods with a larger percentage own group. Logistic regression analyses reveal that mismatches are associated with both a lack of information and inadequate finances, but also may be due to socially desirable responding for whites in particular. Our results provide suggestive evidence of the importance of unpacking the search process more generally and draw attention to what are likely to be productive new future data collection efforts as well as an area potentially ripe for policy interventions. PMID- 26806991 TI - Partially Linear Single Index Cox Regression Model in Nested Case-Control Studies. AB - The nested case-control (NCC) design is widely used in epidemiologic studies as a cost-effective subcohort sampling method to study the association between a disease and its potential risk factors. NCC data are commonly analyzed using Thomas' partial likelihood approach under the Cox proportional hazards model assumption. However, the linear modeling form in the Cox model may be insufficient for practical applications, especially when there are a large number of risk factors under investigation. In this paper, we consider a partially linear single index proportional hazard model, which includes a linear component for covariates of interest to yield easily interpretable results and a nonparametric single index component to adjust for multiple confounders effectively. We propose to approximate the nonparametric single index function by polynomial splines and estimate the parameters of interest using an iterative algorithm based on the partial likelihood. Asymptotic properties of the resulting estimators are established. The proposed methods are evaluated using simulations and applied to an NCC study of ovarian cancer. PMID- 26806992 TI - Different methods to alter surface morphology of high aspect ratio structures. AB - In various applications such as neural prostheses or solar cells, there is a need to alter the surface morphology of high aspect ratio structures so that the real surface area is greater than geometrical area. The change in surface morphology enhances the devices functionality. One of the applications of altering the surface morphology is of neural implants such as the Utah electrode array (UEA) that communicate with single neurons by charge injection induced stimulation or by recording electrical neural signals. For high selectivity between single cells of the nervous system, the electrode surface area is required to be as small as possible, while the impedance is required to be as low as possible for good signal to noise ratios (SNR) during neural recording. For stimulation, high charge injection and charge transfer capacities of the electrodes are required, which increase with the electrode surface. Traditionally, researchers have worked with either increasing the roughness of the existing metallization (Platinum grey, black) or other materials such as Iridium Oxide and PEDOT. All of these previously investigated methods lead to more complicated metal deposition processes that are difficult to control and often have a critical impact on the mechanical properties of the metal films. Therefore, a modification of the surface underneath the electrode's coating will increase its surface area while maintaining the standard and well controlled metal deposition process. In this work, the surfaces of the Silicon micro-needles were engineered by creating a defined microstructure on the electrodes surface using several methods such as Laser ablation, focused ion beam, sputter etching, reactive ion etching (RIE) and deep reactive ion etching (DRIE). The surface modification processes were optimized for the high aspect ratio Silicon structures of the UEA. The increase in real surface area while maintaining the geometrical surface area was verified using scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). The best results were obtained by DRIE induced surface morphology. Decreases in impedance values of electrodes up to 76 % indicate the successful surface engineering of the high aspect ratio Silicon structures. PMID- 26806993 TI - Outlier Identification in Model-Based Cluster Analysis. AB - In model-based clustering based on normal-mixture models, a few outlying observations can influence the cluster structure and number. This paper develops a method to identify these, however it does not attempt to identify clusters amidst a large field of noisy observations. We identify outliers as those observations in a cluster with minimal membership proportion or for which the cluster-specific variance with and without the observation is very different. Results from a simulation study demonstrate the ability of our method to detect true outliers without falsely identifying many non-outliers and improved performance over other approaches, under most scenarios. We use the contributed R package MCLUST for model-based clustering, but propose a modified prior for the cluster-specific variance which avoids degeneracies in estimation procedures. We also compare results from our outlier method to published results on National Hockey League data. PMID- 26806994 TI - Household Incarceration in Early Adolescence and Risk of Premarital First Birth. AB - In the second half of the 20th century, the United States experienced a massive increase in incarceration. In response to this growth, a burgeoning scholarship has sought to explore the collateral consequences of incarceration for young children. However, this scholarship has less frequently explored the impact of incarceration on long-term outcomes, how incarceration experienced in periods other than early childhood impacts children, and whether the incarceration of family members other than parents has negative implications for children. Using data from the children of the mothers in the National Longitudinal Survey of Youth, I explore whether household incarceration experienced in early adolescence is associated with a child's risk of growing up to have a premarital first birth. The results suggest that, even after including a rich set of covariates, children who experience household incarceration in early adolescence are at greater risk of having a premarital first birth, particularly when the father or an external household member is incarcerated. PMID- 26806995 TI - The Effect of Race/Ethnicity on the Relation between Substance Use Disorder Diagnosis and Substance Use Treatment Receipt among Male Serious Adolescent Offenders. AB - The high rates of substance disorders in the juvenile justice system, as well as the relation between substance use and reoffending, suggest the importance of substance use treatment service and understanding the factors that influence treatment provision. The current study tested whether race/ethnicity affects the relation between substance use disorder diagnosis and the receipt of substance use treatment services among a sample of male serious juvenile offenders (N=638). Findings showed that among adolescents with a substance use disorder diagnosis, there were no race/ethnicity differences in substance use treatment receipt. However, among adolescents without a substance use disorder diagnosis, non Hispanic Caucasians were more likely to receive substance use treatment than were Hispanics or African-Americans. Additionally, findings showed that there were race/ethnicity differences in service receipt at moderate levels of substance use problems, such that non-Hispanic Caucasians were more likely to receive substance use treatment than Hispanics or African-Americans. There were no race/ethnicity differences in treatment receipt when substance use problems were either very severe or very low. Results suggest that race/ethnicity may play a role in service provision in the juvenile justice system when levels of need are less clear. PMID- 26806996 TI - Displacement-length scaling of brittle faults in ductile shear. AB - Within a low-grade ductile shear zone, we investigated exceptionally well exposed brittle faults, which accumulated antithetic slip and rotated into the shearing direction. The foliation planes of the mylonitic host rock intersect the faults approximately at their centre and exhibit ductile reverse drag. Three types of brittle faults can be distinguished: (i) Faults developing on pre-existing K feldspar/mica veins that are oblique to the shear direction. These faults have triclinic flanking structures. (ii) Wing cracks opening as mode I fractures at the tips of the triclinic flanking structures, perpendicular to the shear direction. These cracks are reactivated as faults with antithetic shear, extend from the parent K-feldspar/mica veins and form a complex linked flanking structure system. (iii) Joints forming perpendicular to the shearing direction are deformed to form monoclinic flanking structures. Triclinic and monoclinic flanking structures record elliptical displacement-distance profiles with steep displacement gradients at the fault tips by ductile flow in the host rocks, resulting in reverse drag of the foliation planes. These structures record one of the greatest maximum displacement/length ratios reported from natural fault structures. These exceptionally high ratios can be explained by localized antithetic displacement along brittle slip surfaces, which did not propagate during their rotation during surrounding ductile flow. PMID- 26806997 TI - Polyhalite microfabrics in an Alpine evaporite melange: Hallstatt, Eastern Alps. AB - In the Hallstatt salt mine (Austria), polyhalite rocks occur in 0.5-1 m thick and several metre long tectonic lenses within the protocataclasite to protomylonite matrix of the Alpine Haselgebirge Fm.. Thin section analysis of Hallstatt polyhalites reveals various fabric types similar to metamorphic rocks of crust forming minerals, e.g. quartz and feldspar. Polyhalite microfabrics from Hallstatt include: (1) polyhalite mylonites, (2) metamorphic reaction fabrics, (3) vein-filling, fibrous polyhalite and (4) cavity-filling polyhalite. The polyhalite mylonites contain a wide range of shear fabrics commonly known in mylonitic quartzo-feldspathic shear zones within the ductile crust and developed from a more coarse-grained precursor rock. The mylonites are partly overprinted by recrystallised, statically grown polyhalite grains. Metamorphic reaction fabrics of polyhalite fibres between blodite (or astrakhanite) [Na2Mg(SO4)2.4H2O] and anhydrite have also been found. According to previous reports, blodite may occur primarily as nodules or intergrown with loweite. Reaction fabrics may have formed by exsolution, (re-)crystallisation, parallel growth or replacement. This fabric type was only found in one sample in relation with the decomposition of blodite at ca. 61 degrees C in the presence of halite or slightly above, testifying, therefore, a late stage prograde fabric significantly younger than the main polyhalite formation. PMID- 26806998 TI - The structure of the Hallstatt evaporite body (Northern Calcareous Alps, Austria): A compressive diapir superposed by strike-slip shear? AB - Based on old detailed mining maps and own observations in the Hallstatt salt mine, we reinterpret the structure of the Hallstatt evaporite body of the Upper Permian to Lower Triassic Haselgebirge Fm. within the Northern Calcareous Alps (NCA). The Haselgebirge Fm. represents a rocksalt mylonite with abundant lenses of sulphates, mudstones and limestones. In comparison to published results of analogue modeling we interpret the present shape of the Hallstatt body as a WNW ESE elongated compressive teardrop-like diapir. This is overprinted by NNE-SSW shortening and dominantly sinistral shearing along a W-trending shear zone. The internal structure shows steeply dipping rock units and foliation. Earlier dextral ductile shear fabrics of likely late Early Cretaceous age are preserved in sulphate rocks and are subsequently overprinted by mylonitic fabrics in rocksalt and cataclastic fabrics in other rocks. The low strength of halite results in recent subvertical shortening and a strain rate [Formula: see text] of 8 * 10-10 [s-1] is deduced from deformed subhorizontal boreholes. This value is similar to such strain rates (10-10 to 10-9 s-1) estimated by the halite grain size distribution from other salt mines in the NCA and thus indicative of sub recent formation of the halite microfabrics. PMID- 26806999 TI - Sources of water column methylmercury across multiple estuaries in the Northeast U.S. AB - Estuarine water column methylmercury (MeHg) is an important driver of mercury (Hg) bioaccumulation in pelagic organisms and thus it is necessary to understand the sources and processes affecting environmental levels of MeHg. Increases in water column MeHg concentrations can ultimately be transferred to fish consumed by humans, but despite this, the sources of MeHg to the estuarine water column are still poorly understood. Here we evaluate MeHg sources across 4 estuaries and 10 sampling sites and examine the distributions and partitioning of sediment and water column MeHg across a geographic range (Maine to New Jersey). Our study sites present a gradient in the concentrations of sediment, pore water and water column Hg species. Suspended particle MeHg ranged from below detection to 187 pmol g-1, dissolved MeHg from 0.01 to 0.68 pM, and sediment MeHg from 0.01 to 109 pmol g-1. Across multiple estuaries, dissolved MeHg correlated with Hg species in the water column, and sediment MeHg correlated with sediment total Hg (HgT). Water column MeHg did not correlate well with sediment Hg across estuaries, indicating that sediment concentrations were not a good predictor of water MeHg concentrations. This is an unexpected finding since it has been shown that MeHg production from inorganic Hg2+ within sediment is the primary source of MeHg to coastal waters. Additional sources of MeHg regulate water column MeHg levels in some of the shallow estuaries included in this study. PMID- 26807000 TI - Exploration of the Oxazolidinthione Protecting System for the Synthesis of Sialic Acid Glycosides. AB - An N-acetyl oxazolidinthione protected sialyl thioglycoside was synthesized and its use as a sialyl donor studied. The strongly electron-withdrawing nature of the oxazolidinthione moiety is such that activation could not be achieved at -78 degrees C. Couplings were therefore conducted at the lowest convenient temperature (-50 degrees C). Glycosides were formed in good yield but in two out three cases studied selectivities were lower than those seen with the corresponding N-acetyl oxazoldinone protected donor. The resulting N-acetyl oxazolidinthione protectd disaccharides were converted to the corresponding N acetyl oxazolidinones by treatment with N-iodosuccinimide and triflic acid in the presence of water at 0 degrees C. PMID- 26807001 TI - Serving Transgender Youth: Challenges, Dilemmas and Clinical Examples. AB - Historically, many gender variant individuals have lived in a chronic state of conflict between self-understanding and physical being, one in which there was a continual misalignment between others' perceptions of them and their internal self-perception of gender. Only recently have professionals from mental health and medical realms come together to provide services to these youth. This paper describes an innovative program: the first mental health and medical multidisciplinary clinic housed in a pediatric academic center in North America to serve the needs of gender variant youth. We describe our model of care, focusing on the psychologist's role within a multidisciplinary team and the mental health needs of the youth and families assisted. We highlight clinical challenges and provide practice clinical vignettes to illuminate the psychologist's critical role. PMID- 26807002 TI - Cross-Language Associations in the Development of Preschoolers' Receptive and Expressive Vocabulary. AB - The increasing population of dual language learners (DLLs) entering preschool classrooms highlights a continued need for research on the development of dual language acquisition, and specifically vocabulary skills, in this age group. This study describes young DLL children's (N = 177) vocabulary development in both English and Spanish simultaneously, and how vocabulary skills in each language relate to one another, during a contextual shift that places greater emphasis on the acquisition of academic English language skills. Findings demonstrated that DLL preschoolers made gains in vocabulary in both languages with more change evidenced in receptive, in comparison to expressive, vocabulary as well as in English in comparison to Spanish. When examining whether children's vocabulary scores in one language at the beginning of preschool interact with their vocabulary scores in the other language to predict vocabulary growth, no significant associations were found for receptive vocabulary. In contrast, the interaction between initial English and Spanish expressive vocabulary scores was negatively related to growth in English expressive vocabulary. This cross language association suggests that children who have low expressive vocabulary skills in both languages tend to grow faster in their English expressive vocabulary. The study extends previous work on dual language development by examining growth in expressive and receptive vocabulary in both English and Spanish. It also provides suggestions for future work to inform a more comprehensive understanding of DLL children's development in both languages. PMID- 26807003 TI - One-to-One Assistant Engagement in Autism Support Classrooms. AB - Classroom assistants and one-to-one assistants are an important part of the staffing structure of many autism support classrooms. Limited studies, however, have examined how one-to-one assistants spend their time in the classroom. The purpose of this article was to examine the percentage of time one-to-one assistants were engaged in instruction or support of students with autism and to determine the factors associated with their engagement. Direct observations were conducted in 46 autism support classrooms. Teachers and classroom assistants were engaged in instruction or support 98% and 91% of the time, respectively. One-to one assistants were engaged in instruction or support 57% of the time. Classroom assistants' and one-to-one assistants' engagement was significantly correlated. The low rate of one-to-one assistants' engagement suggests an inefficient use of an important resource. PMID- 26807004 TI - Standards of Medical Care in Diabetes-2016 Abridged for Primary Care Providers. PMID- 26807005 TI - Modern Medicine Nearly Killed Me. PMID- 26807006 TI - Incorrect Insulin Administration: A Problem That Warrants Attention. AB - In Brief Incorrect administration of insulin (e.g., too little, too much, or at wrong times) can result in transient and serious hypo- and hyperglycemia, wide glycemic excursions, and diabetic ketoacidosis. The authors systematically assessed the insulin-related knowledge and injection skills of a sample of adults with diabetes and found that errors in self-administering insulin, including choosing an incorrect insulin dose, were common. Injection site selection and diabetes numeracy were also concerns. Correct timing of injections and confidence in choosing correct doses, but not skills scores, related to better A1C and blood glucose levels. PMID- 26807007 TI - Role of Emerging Insulin Technologies in the Initiation and Intensification of Insulin Therapy for Diabetes in Primary Care. AB - In Brief This article explores some of the reasons for the delay in insulin initiation in primary care and evaluates new approaches to insulin therapy that may address these barriers and, therefore, improve insulin use by primary care providers. PMID- 26807009 TI - Concurrence of Lipoatrophy and Lipohypertrophy in Children With Type 1 Diabetes Using Recombinant Human Insulin: Two Case Reports. PMID- 26807008 TI - Overcoming Weight Bias in the Management of Patients With Diabetes and Obesity. PMID- 26807010 TI - Oral Manifestations of Diabetes. PMID- 26807011 TI - The Affordable Care Act Insurance Reforms: Where Are We Now, and What's Next? PMID- 26807012 TI - Analysis of Protein-protein Interaction Interface between Yeast Mitochondrial Proteins Rim1 and Pif1 Using Chemical Cross-linking Mass Spectrometry. AB - Defining protein-protein contacts is a challenging problem and cross-linking is a promising solution. Here, we present a case of mitochondrial single strand binding protein Rim1 and helicase Pif1, an interaction first observed in immuno affinity pull-down from yeast cells using Pif1 bait. We found that only the short succinimidyl-diazirine cross-linker or formaldehyde captured the interaction between recombinant Rim1 and Pif1. In addition, Pif1 needed to be stripped of its N-terminal and C-terminal domains, and Rim1's C-terminus needed to be modified for the cross-linked product to become visible. Our report is an example of a non trivial analysis, where a previously identified stable interaction escapes initial capture with cross-linking agents and requires substantial modification to recombinant proteins and fine-tuning of the mass spectrometry-based methods for the cross-links to become detectable. We used high resolution mass spectrometry to detect the cross-linked peptides. A 1:1 mixture of 15N and 14N labeled Rim1 was used to validate the cross-links by their mass shift in the LC MS profiles. Two sites on Rim1 were confirmed: 1) the N-terminus, and 2) the K29 residue. Performing cross-linking with a K29A variant visibly reduced the cross linked product. Further, K29A-Rim1 showed a five-fold lower affinity to single stranded DNA compared to wild-type Rim1. Both the K29A variant and wild type Rim1 showed similar degrees of stimulation of Pif1 helicase activity. We propose structural models of the Pif1-Rim1 interaction and discuss its functional significance. Our work represents a non-trivial protein-protein interface analysis and demonstrates utility of short and non-specific cross-linkers. PMID- 26807013 TI - Multidimensional Separation Using HILIC and SCX Pre-fractionation for RP LC-MS/MS Platform with Automated Exclusion List-based MS Data Acquisition with Increased Protein Quantification. AB - Liquid chromatography-mass spectrometry (LC-MS) based proteomics is one of the most widely used analytical platforms for global protein discovery and quantification. One of the challenges is the difficulty of identifying low abundance biomarker proteins from limited biological samples. Extensive fractionation could expand proteomics dynamic range, however, at the cost of high sample and time consumption. Extensive fractionation would increase the sample need and the labeling cost. Also quantitative proteomics depending on high resolution MS have the limitation of spectral acquisition speed. Those practical problems hinder the in-depth quantitative proteomics analysis such as tandem mass tag (TMT) experiments. We found the joint use of hydrophilic interaction liquid chromatography (HILIC) and strong cation exchange Chromatography (SCX) prefractionation at medium level could improve MS/MS efficiency, increase proteome coverage, shorten analysis time and save valuable samples. In addition, we scripted a program, Exclusion List Convertor (ELC), which automates and streamlines data acquisition workflow using the precursor ion exclusion (PIE) method. PIE reduces redundancy of high abundance MS/MS analyses by running replicates of the sample. The precursor ions detected in the initial run(s) are excluded for MS/MS in the subsequent run. We compared PIE methods with standard data dependent acquisition (DDA) methods running replicates without PIE for their effectiveness in quantifying TMT-tagged peptides and proteins in mouse tears. We quantified a total of 845 proteins and 1401 peptides using the PIE workflow, while the DDA method only resulted in 347 proteins and 731 peptides. This represents a 144% increase of protein identifications as a result of PIE analysis. PMID- 26807014 TI - Empirically Estimable Classification Bounds Based on a Nonparametric Divergence Measure. AB - Information divergence functions play a critical role in statistics and information theory. In this paper we show that a non-parametric f-divergence measure can be used to provide improved bounds on the minimum binary classification probability of error for the case when the training and test data are drawn from the same distribution and for the case where there exists some mismatch between training and test distributions. We confirm the theoretical results by designing feature selection algorithms using the criteria from these bounds and by evaluating the algorithms on a series of pathological speech classification tasks. PMID- 26807015 TI - Vascular Perfusion of Implanted Human Engineered Cardiac Tissue. AB - Regeneration of muscle tissue in the heart after a myocardial infarction requires delivering human cardiomyocytes that will survive and integrate with the host myocardium. Of primary importance is the development of a vascular bed to nourish the implanted cardiomyocytes, whether delivered via injection or in engineered tissues. Co-culture of hESC-derived cardiomyocytes, human endothelial cells, and human stromal cells provides a prevascular network in scaffold-free engineered tissue patches. As a result, the density of lumen structures in the graft increases by histological analysis, but perfusion of these vessels must be assessed. In this study, we develop a method for perfusing the host heart and engineered human cardiac tissue graft that is compatible with confocal microscopy for obtaining 2D images and 3D reconstructions of the graft vasculature. We demonstrate that, although vascular density is substantial in the grafts, flow remains sluggish. Further improvements in arterial remodeling or vascular engineering are required for physiological levels of blood flow. PMID- 26807016 TI - Barriers to Effective Implementation of Programs for the Prevention of Workplace Violence in Hospitals. AB - Effective workplace violence (WPV) prevention programs are essential, yet challenging to implement in healthcare. The aim of this study was to identify major barriers to implementation of effective violence prevention programs. After reviewing the related literature, the authors describe their research methods and analysis and report the following seven themes as major barriers to effective implementation of workplace violence programs: a lack of action despite reporting; varying perceptions of violence; bullying; profit-driven management models; lack of management accountability; a focus on customer service; and weak social service and law enforcement approaches to mentally ill patients. The authors discuss their findings in light of previous studies and experiences and offer suggestions for decreasing WPV in healthcare settings. They conclude that although many of these challenges to effective implementation of workplace violence programs are both within the program itself and relate to broader industry and societal issues, creative innovations can address these issues and improve WPV prevention programs. PMID- 26807017 TI - Neural circuit remodeling and structural plasticity in the cortex during chronic pain. AB - Damage in the periphery or spinal cord induces maladaptive plastic changes along the somatosensory nervous system from the periphery to the cortex, often leading to chronic pain. Although the role of neural circuit remodeling and structural synaptic plasticity in the 'pain matrix' cortices in chronic pain has been thought as a secondary epiphenomenon to altered nociceptive signaling in the spinal cord, progress in whole brain imaging studies on human patients and animal models has suggested a possibility that plastic changes in cortical neural circuits may actively contribute to chronic pain symptoms. Furthermore, recent development in two-photon microscopy and fluorescence labeling techniques have enabled us to longitudinally trace the structural and functional changes in local circuits, single neurons and even individual synapses in the brain of living animals. These technical advances has started to reveal that cortical structural remodeling following tissue or nerve damage could rapidly occur within days, which are temporally correlated with functional plasticity of cortical circuits as well as the development and maintenance of chronic pain behavior, thereby modifying the previous concept that it takes much longer periods (e.g. months or years). In this review, we discuss the relation of neural circuit plasticity in the 'pain matrix' cortices, such as the anterior cingulate cortex, prefrontal cortex and primary somatosensory cortex, with chronic pain. We also introduce how to apply long-term in vivo two-photon imaging approaches for the study of pathophysiological mechanisms of chronic pain. PMID- 26807018 TI - cAMP induction by ouabain promotes endothelin-1 secretion via MAPK/ERK signaling in beating rabbit atria. AB - Adenosine 3',5'-cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the Na(+)-K(+)-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain (3.0 umol/L) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabain-increased atrial dynamics was blocked by KB-R7943 (3.0 umol/L), an inhibitor for reverse mode of Na(+)-Ca(2+) exchangers (NCX), but did not by L type Ca(2+) channel blocker nifedipine (1.0 umol/L) or protein kinase A (PKA) selective inhibitor H-89 (3.0 umol/L). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline (100.0 umol/L), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP (0.5 umol/L) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 (30 umol/L), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds. PMID- 26807019 TI - Carnosic acid protects against acetaminophen-induced hepatotoxicity by potentiating Nrf2-mediated antioxidant capacity in mice. AB - Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure. The study aimed to investigate the protective effect of carnosic acid (CA) on APAP-induced acute hepatotoxicity and its underlying mechanism in mice. To induce hepatotoxicity, APAP solution (400 mg/kg) was administered into mice by intraperitoneal injection. Histological analysis revealed that CA treatment significantly ameliorated APAP-induced hepatic necrosis. The levels of both alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced by CA treatment. Moreover, CA treatment significantly inhibited APAP induced hepatocytes necrosis and lactate dehydrogenase (LDH) releasing. Western blot analysis showed that CA abrogated APAP-induced cleaved caspase-3, Bax and phosphorylated JNK protein expression. Further results showed that CA treatment markedly inhibited APAP-induced pro-inflammatory cytokines TNF-alpha, IL-1beta, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated IkappaBalpha and p65 protein in the liver. In addition, CA treatment reduced APAP- induced hepatic malondialdehyde (MDA) contents and reactive oxygen species (ROS) accumulation. Conversely, hepatic glutathione (GSH) level was increased by administration of CA in APAP-treated mice. Mechanistically, CA facilitated Nrf2 translocation into nuclear through blocking the interaction between Nrf2 and Keap1, which, in turn, upregulated anti-oxidant genes mRNA expression. Taken together, our results indicate that CA facilitates Nrf2 nuclear translocation, causing induction of Nrf2-dependent genes, which contributes to protection from acetaminophen hepatotoxicity. PMID- 26807020 TI - Activation of K(+) channel by 1-EBIO rescues the head and neck squamous cell carcinoma cells from Ca(2+) ionophore-induced cell death. AB - Ion channels in carcinoma and their roles in cell proliferation are drawing attention. Intracellular Ca(2+) ([Ca(2+)]i)-dependent signaling affects the fate of cancer cells. Here we investigate the role of Ca(2+)-activated K(+) channel (SK4) in head and neck squamous cell carcinoma cells (HNSCCs) of different cell lines; SNU-1076, OSC-19 and HN5. Treatment with 1 uM ionomycin induced cell death in all the three cell lines. Whole-cell patch clamp study suggested common expressions of Ca(2+)-activated Cl(-) channels (Ano-1) and Ca(2+)-activated nonselective cation channels (CAN). 1-EBIO, an activator of SK4, induced outward K(+) current (ISK4) in SNU-1076 and OSC-19. In HN5, ISK4 was not observed or negligible. The 1-EBIO-induced current was abolished by TRAM-34, a selective SK4 blocker. Interestingly, the ionomycin-induced cell death was effectively prevented by 1-EBIO in SNU-1076 and OSC-19, and the rescue effect was annihilated by combined TRAM-34. Consistent with the lower level of ISK4, the rescue by 1 EBIO was least effective in HN5. The results newly demonstrate the role of SK4 in the fate of HNSCCs under the Ca(2+) overloaded condition. Pharmacological modulation of SK4 might provide an intriguing novel tool for the anti-cancer strategy in HNSCC. PMID- 26807021 TI - Toxicokinetics of paraquat in Korean patients with acute poisoning. AB - To conduct a kinetic study of paraquat (PQ), we investigated 9 patients with acute PQ intoxication. All of them ingested more than 20 ml of undiluted PQ herbicide to commit suicide and arrived at our hospital early, not later than 7 h after PQ ingestion. The urine dithionite test for PQ in all of the nine patients was strongly positive at emergency room. Blood samples were obtained every 30 min for the first 2~3 h and then every 1 or 2 h, as long as the clinical progression was stable among the patients for 30 h after PQ ingestion. The area under the plasma concentration-time curve (AUCinf), which was extrapolated to infinity, was calculated using the trapezoidal rule. Toxicokinetic parameters, such as the terminal elimination half-life, apparent oral clearance, and apparent volume of distribution (Vd/F) were calculated. The maximum PQ concentration (Cmax) and the time to reach maximum PQ concentration (Tmax) were also obtained. Plasma PQ concentrations in nine patients were well described by a bi-exponential curve with a mean terminal elimination half-life of 13.1+/-6.8 h. Cmax and AUCinf were 20.8+/-25.7 mg/l and 172.5+/-160.3 h.mg/l, respectively. Apparent volume of distribution and apparent oral clearance were 50.9+/-61.3 l/kg and 173.4+/-111.2 l/h, respectively. There were a significant correlation (r =0.84; p<0.05) between the PQ amount ingested and Cmax. AUCinf also showed a significant correlation (r =0.83; p<0.05) with the PQ amount ingested. These correlations provide evidence that PQ has dose-linear toxicokinetic characteristics. PMID- 26807022 TI - Epigallocatechin-3-gallate rescues LPS-impaired adult hippocampal neurogenesis through suppressing the TLR4-NF-kappaB signaling pathway in mice. AB - Adult hippocampal dentate granule neurons are generated from neural stem cells (NSCs) in the mammalian brain, and the fate specification of adult NSCs is precisely controlled by the local niches and environment, such as the subventricular zone (SVZ), dentate gyrus (DG), and Toll-like receptors (TLRs). Epigallocatechin-3-gallate (EGCG) is the main polyphenolic flavonoid in green tea that has neuroprotective activities, but there is no clear understanding of the role of EGCG in adult neurogenesis in the DG after neuroinflammation. Here, we investigate the effect and the mechanism of EGCG on adult neurogenesis impaired by lipopolysaccharides (LPS). LPS-induced neuroinflammation inhibited adult neurogenesis by suppressing the proliferation and differentiation of neural stem cells in the DG, which was indicated by the decreased number of Bromodeoxyuridine (BrdU)-, Doublecortin (DCX)- and Neuronal Nuclei (NeuN)-positive cells. In addition, microglia were recruited with activatingTLR4-NF-kappaB signaling in the adult hippocampus by LPS injection. Treating LPS-injured mice with EGCG restored the proliferation and differentiation of NSCs in the DG, which were decreased by LPS, and EGCG treatment also ameliorated the apoptosis of NSCs. Moreover, pro inflammatory cytokine production induced by LPS was attenuated by EGCG treatment through modulating the TLR4-NF-kappaB pathway. These results illustrate that EGCG has a beneficial effect on impaired adult neurogenesis caused by LPSinduced neuroinflammation, and it may be applicable as a therapeutic agent against neurodegenerative disorders caused by inflammation. PMID- 26807024 TI - Allogeneic clonal mesenchymal stem cell therapy for refractory graft-versus-host disease to standard treatment: a phase I study. AB - Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose (1*10(6) cells/kg), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial. PMID- 26807023 TI - Effects of CoCl2 on multi-lineage differentiation of C3H/10T1/2 mesenchymal stem cells. AB - Mesenchymal stem cells (MSCs) in the bone marrow and other somatic tissues reside in an environment with relative low oxygen tension. Cobalt chloride (CoCl2) can mimic hypoxic conditions through transcriptional changes of some genes including hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF). This study evaluated the potential role of CoCl2 preconditioning on multi-lineage differentiation of C3H/10T1/2, a murine MSC line to understand its possible molecular mechanisms in vitro. CoCl2 treatment of MSCs markedly increased HIF-1alpha and VEGF mRNA, and protein expression of HIF-1alpha. Temporary preconditioning of MSCs with CoCl2 induced up-regulation of osteogenic markers including alkaline phosphatase, osteocalcin, and type I collagen during osteogenic differentiation, followed by enhanced mineralization. CoCl2 also increased chondrogenic markers including aggrecan, sox9, and type II collagen, and promoted chondrocyte differentiation. CoCl2 suppressed the expression of adipogenic markers including PPARgamma, aP2, and C/EBPalpha, and inhibited adipogenesis. Temporary preconditioning with CoCl2 could affect the multi-lineage differentiation of MSCs. PMID- 26807025 TI - Cardamonin inhibits agonist-induced vascular contractility via Rho-kinase and MEK inhibition. AB - The present study was undertaken to investigate the influence of cardamonin on vascular smooth muscle contractility and to determine the mechanism(s) involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Cardamonin significantly relaxed fluoride-, phenylephrine-, and phorbol ester-induced vascular contractions, suggesting that it has an anti-hypertensive effect on agonist induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, cardamonin significantly inhibited the fluoride-induced increase in pMYPT1 level and phenylephrine-induced increase in pERK1/2 level, suggesting inhibition of Rho-kinase and MEK activity and subsequent phosphorylation of MYPT1 and ERK1/2. This study provides evidence that the relaxing effect of cardamonin on agonist-induced vascular contraction regardless of endothelial function involves inhibition of Rho-kinase and MEK activity. PMID- 26807026 TI - Blockade of Kv1.5 by paroxetine, an antidepressant drug. AB - Paroxetine, a selective serotonin reuptake inhibitor (SSRI), has been reported to have an effect on several ion channels including human ether-a-go-go-related gene in a SSRI-independent manner. These results suggest that paroxetine may cause side effects on cardiac system. In this study, we investigated the effect of paroxetine on Kv1.5, which is one of cardiac ion channels. The action of paroxetine on the cloned neuronal rat Kv1.5 channels stably expressed in Chinese hamster ovary cells was investigated using the whole-cell patch-clamp technique. Paroxetine reduced Kv1.5 whole-cell currents in a reversible concentration dependent manner, with an IC 50 value and a Hill coefficient of 4.11 uM and 0.98, respectively. Paroxetine accelerated the decay rate of inactivation of Kv1.5 currents without modifying the kinetics of current activation. The inhibition increased steeply between -30 and 0 mV, which corresponded with the voltage range for channel opening. In the voltage range positive to 0 mV, inhibition displayed a weak voltage dependence, consistent with an electrical distance delta of 0.32. The binding (k+1) and unbinding (k-1) rate constants for paroxetine-induced block of Kv1.5 were 4.9 uM(-1)s(-1) and 16.1 s(-1), respectively. The theoretical K D value derived by k-1/k+1 yielded 3.3 uM. Paroxetine slowed the deactivation time course, resulting in a tail crossover phenomenon when the tail currents, recorded in the presence and absence of paroxetine, were superimposed. Inhibition of Kv1.5 by paroxetine was use-dependent. The present results suggest that paroxetine acts on Kv1.5 currents as an open-channel blocker. PMID- 26807027 TI - Effect of D-glucose feeding on mortality induced by sepsis. AB - Sepsis is the life-threatening response to infection which can lead to tissue damage, organ failure, and death. In the current study, the effect of orally administered D-glucose on the mortality and the blood glucose level induced by D Galactosamine (GaLN)/lipopolysaccharide (LPS)-induced sepsis was examined in ICR mice. After various amounts of D-glucose (from 1 to 8 g/kg) were orally fed, sepsis was induced by injecting intraperitoneally (i.p.) the mixture of GaLN /LPS. Oral pre-treatment with D-glucose dose-dependently increased the blood glucose level and caused a reduction of sepsis-induced mortality. The oral post treatment with D-glucose (8 g/kg) up to 3 h caused an elevation of the blood glucose level and protected the mortality observed in sepsis model. However, D glucose post-treated at 6, 9, or 12 h after sepsis induction did not affect the mortality and the blood glucose level induced by sepsis. Furthermore, the intrathecal (i.t.) pretreatment once with pertussis toxin (PTX; 0.1 ug/5 ml) for 6 days caused a reduction of D-glucose-induced protection of mortality and hyperglycemia. Furthermore, once the hypoglycemic state is continued up to 6 h after sepsis initiated, sepsis-induced mortality could not be reversed by D glucose fed orally. Based on these findings, it is assumed that the hypoglycemic duration between 3 and 6 h after the sepsis induction may be a critical time of period for the survival. D-glucose-induced protective effect against sepsis induced mortality appears to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Finally, the production of hyperglycemic state may be critical for the survival against the sepsis-induced mortality. PMID- 26807028 TI - (E)-3-(3-methoxyphenyl)-1-(2-pyrrolyl)-2-propenone displays suppression of inflammatory responses via inhibition of Src, Syk, and NF-kappaB. AB - (E)-3-(3-methoxyphenyl)-1-(2-pyrrolyl)-2-propenone (MPP) is an aldol condensation product resulting from pyrrole-2-carbaldehyde and m- and p- substituted acetophenones. However, its biological activity has not yet been evaluated. Since it has been reported that some propenone-type compounds display anti-inflammatory activity, we investigated whether MPP could negatively modulate inflammatory responses. To do this, we employed lipopolysaccharide (LPS)-stimulated macrophage like RAW264.7 cells and examined the inhibitory levels of nitric oxide (NO) production and transcriptional activation, as well as the target proteins involved in the inflammatory signaling cascade. Interestingly, MPP was found to reduce the production of NO in LPS-treated RAW264.7 cells, without causing cytotoxicity. Moreover, this compound suppressed the mRNA levels of inflammatory genes, such as inducible NO synthase (iNOS) and tumor necrosis factor (TNF) alpha. Using luciferase reporter gene assays performed in HEK293 cells and immunoblotting analysis with nuclear protein fractions, we determined that MPP reduced the transcriptional activation of nuclear factor (NF)-kappaB. Furthermore, the activation of a series of upstream signals for NF-kappaB activation, composed of Src, Syk, Akt, and IkappaBalpha, were also blocked by this compound. It was confirmed that MPP was able to suppress autophosphorylation of overexpressed Src and Syk in HEK293 cells. Therefore, these results suggest that MPP can function as an anti-inflammatory drug with NF-kappaB inhibitory properties via the suppression of Src and Syk. PMID- 26807029 TI - Brief low [Mg(2+)]o-induced Ca(2+) spikes inhibit subsequent prolonged exposure induced excitotoxicity in cultured rat hippocampal neurons. AB - Reducing [Mg(2+)]o to 0.1 mM can evoke repetitive [Ca(2+)]i spikes and seizure activity, which induces neuronal cell death in a process called excitotoxicity. We examined the issue of whether cultured rat hippocampal neurons preconditioned by a brief exposure to 0.1 mM [Mg(2+)]o are rendered resistant to excitotoxicity induced by a subsequent prolonged exposure and whether Ca(2+) spikes are involved in this process. Preconditioning by an exposure to 0.1 mM [Mg(2+)]o for 5 min inhibited significantly subsequent 24 h exposure-induced cell death 24 h later (tolerance). Such tolerance was prevented by both the NMDA receptor antagonist D AP5 and the L-type Ca(2+) channel antagonist nimodipine, which blocked 0.1 mM [Mg(2+)]o-induced [Ca(2+)]i spikes. The AMPA receptor antagonist NBQX significantly inhibited both the tolerance and the [Ca(2+)]i spikes. The intracellular Ca(2+) chelator BAPTA-AM significantly prevented the tolerance. The nonspecific PKC inhibitor staurosporin inhibited the tolerance without affecting the [Ca(2+)]i spikes. While Go6976, a specific inhibitor of PKCalpha had no effect on the tolerance, both the PKCepsilon translocation inhibitor and the PKCzeta pseudosubstrate inhibitor significantly inhibited the tolerance without affecting the [Ca(2+)]i spikes. Furthermore, JAK-2 inhibitor AG490, MAPK kinase inhibitor PD98059, and CaMKII inhibitor KN-62 inhibited the tolerance, but PI-3 kinase inhibitor LY294,002 did not. The protein synthesis inhibitor cycloheximide significantly inhibited the tolerance. Collectively, these results suggest that low [Mg(2+)]o preconditioning induced excitotoxic tolerance was directly or indirectly mediated through the [Ca(2+)]i spike-induced activation of PKCepsilon and PKCxi, JAK-2, MAPK kinase, CaMKII and the de novo synthesis of proteins. PMID- 26807030 TI - Inducibility of human atrial fibrillation in an in silico model reflecting local acetylcholine distribution and concentration. AB - Vagal nerve activity has been known to play a crucial role in the induction and maintenance of atrial fibrillation (AF). However, it is unclear how the distribution and concentration of local acetylcholine (ACh) promotes AF. In this study, we investigated the effect of the spatial distribution and concentration of ACh on fibrillation patterns in an in silico human atrial model. A human atrial action potential model with an ACh-dependent K(+) current (IKAch) was used to examine the effect of vagal activation. A simulation of cardiac wave dynamics was performed in a realistic 3D model of the atrium. A model of the ganglionated plexus (GP) and nerve was developed based on the "octopus hypothesis". The pattern of cardiac wave dynamics was examined by applying vagal activation to the GP areas or randomly. AF inducibility in the octopus hypothesis-based GP and nerve model was tested. The effect of the ACh concentration level was also examined. In the single cell simulation, an increase in the ACh concentration shortened APD90 and increased the maximal slope of the restitution curve. In the 3D simulation, a random distribution of vagal activation promoted wavebreaks while ACh secretion limited to the GP areas did not induce a noticeable change in wave dynamics. The octopus hypothesis-based model of the GP and nerve exhibited AF inducibility at higher ACh concentrations. In conclusion, a 3D in silico model of the GP and parasympathetic nerve based on the octopus model exhibited higher AF inducibility with higher ACh concentrations. PMID- 26807031 TI - Comparison of electrophysiological effects of calcium channel blockers on cardiac repolarization. AB - Dihydropyridine (DHP) calcium channel blockers (CCBs) have been widely used to treat of several cardiovascular diseases. An excessive shortening of action potential duration (APD) due to the reduction of Ca(2+) channel current (I Ca) might increase the risk of arrhythmia. In this study we investigated the electrophysiological effects of nicardipine (NIC), isradipine (ISR), and amlodipine (AML) on the cardiac APD in rabbit Purkinje fibers, voltage-gated K(+) channel currents (I Kr, I Ks) and voltage-gated Na(+) channel current (I Na). The concentration-dependent inhibition of Ca(2+) channel currents (I Ca) was examined in rat cardiomyocytes; these CCBs have similar potency on I Ca channel blocking with IC50 (the half-maximum inhibiting concentration) values of 0.142, 0.229, and 0.227 nM on NIC, ISR, and AML, respectively. However, ISR shortened both APD50 and APD90 already at 1 uM whereas NIC and AML shortened APD50 but not APD90 up to 30 uM. According to ion channel studies, NIC and AML concentration-dependently inhibited I Kr and I Ks while ISR had only partial inhibitory effects (<50% at 30 uM). Inhibition of I Na was similarly observed in the three CCBs. Since the I Kr and I Ks mainly contribute to cardiac repolarization, their inhibition by NIC and AML could compensate for the AP shortening effects due to the block of I Ca. PMID- 26807033 TI - Taxonomic interpretation of chromosomal and mitochondrial DNA variability in the species complex close to Polyommatus (Agrodiaetus) dama (Lepidoptera, Lycaenidae). AB - In this paper, by using combination of molecular and chromosomal markers, populations of Polyommatus (Agrodiaetus) karindus (Riley, 1921) from north-west and central Iran are analyzed. It has been found that taxon usually identified as Polyommatus (Agrodiaetus) karindus is represented in Iran by two geographically separated groups of individuals, strongly differentiated by their karyotypes and mitochondrial haplotypes. It is demonstrated that populations from NW Iran have the haploid chromosome number n = 68, while the haploid chromosome number of Polyommatus (Agrodiaetus) karindus from central Iran is found to be n = 73. Phylogenetic analysis revealed that these groups also differ by at least eight nucleotide substitutions in a 690 bp fragment of the mitochondrial COI gene and form separated groups of clusters in Bayesian inference tree. Thus, population entities from central Iran are described here as a new subspecies Polyommatus (Agrodiaetus) karindus saravandi ssp. n. Strong chromosomal and molecular differentiation are confirmed between Polyommatus (Agrodiaetus) karindus and its sister species, Polyommatus (Agrodiaetus) dama (Staudinger, 1892). PMID- 26807032 TI - The effects of intra-articular resiniferatoxin on monosodium iodoacetate-induced osteoarthritic pain in rats. AB - This study was performed to investigate whether an intra-articular injection of transient receptor potential vanilloid 1 (TRPV1) receptor agonist, resiniferatoxin (RTX) would alleviate behavioral signs of arthritic pain in a rat model of osteoarthritis (OA). We also sought to determine the effect of RTX treatment on calcitonin gene-related peptide (CGRP) expression in the spinal cord. Knee joint inflammation was induced by intra-articular injection of monosodium iodoacetate (MIA, 8 mg/50 ul) and weight bearing percentage on right and left hindpaws during walking, paw withdrawal threshold to mechanical stimulation, and paw withdrawal latency to heat were measured to evaluate pain behavior. Intra-articular administration of RTX (0.03, 0.003 and 0.0003%) at 2 weeks after the induction of knee joint inflammation significantly improved reduction of weight bearing on the ipsilateral hindlimb and increased paw withdrawal sensitivity to mechanical and heat stimuli. The reduction of pain behavior persisted for 3~10 days according to each behavioral test. The MIA induced increase in CGRP immunoreactivity in the spinal cord was decreased by RTX treatment in a dose-dependent manner. The present study demonstrated that a single intra-articular administration of RTX reduced pain behaviors for a relatively long time in an experimental model of OA and could normalize OA associated changes in peptide expression in the spinal cord. PMID- 26807034 TI - Interpretation of mitochondrial diversity in terms of taxonomy: a case study of Hyponephele lycaon species complex in Israel (Lepidoptera, Nymphalidae, Satyrinae). AB - It is difficult to interpret mitochondrial diversity in terms of taxonomy even in cases in which a concordance exists between mitochondrial, ecological and morphological markers. Here we demonstrate this difficulty through a study of Israeli Hyponephele butterflies. We show that samples commonly identified as Hyponephele lycaon are represented on Mount Hermon in Israel by two sympatric groups of individuals distinct both in mitochondrial DNA-barcodes (uncorrected p distance = 3.5%) and hindwing underside pattern. These two groups were collected in different biotopes. They also tended to be different in length of brachia in male genitalia, although the latter character is variable. We reject the hypothesis that the discovered COI haplogroups are selectively neutral intraspecific characters. We hypothesize that they represent: either (1) two different biological species, or (2) a consequence of a strong positive selection acting at intraspecific level and resulting in two intraspecific clusters adapted to low and to high elevations. If we accept the first hypothesis, then provisionally these two haplogroups can be attributed to transpalearctic Hyponephele lycaon sensu stricto and to Hyponephele lycaonoides, previously known from Iran and East Turkey. PMID- 26807035 TI - DNA barcoding reveals twelve lineages with properties of phylogenetic and biological species within Melitaea didyma sensu lato (Lepidoptera, Nymphalidae). AB - The complex of butterfly taxa close to Melitaea didyma includes the traditionally recognized species Melitaea didyma, Melitaea didymoides and Melitaea sutschana, the taxa that were recognized as species only relatively recently (Melitaea latonigena, Melitaea interrupta, Melitaea chitralensis and Melitaea mixta) as well as numerous described subspecies and forms with unclear taxonomic status. Here analysis of mitochondrial DNA barcodes is used to demonstrate that this complex is monophyletic group consisting of at least 12 major haplogroups strongly differentiated with respect to the gene COI. Six of these haplogroups are shown to correspond to six of the above-mentioned species (Melitaea didymoides, Melitaea sutschana, Melitaea latonigena, Melitaea interrupta, Melitaea chitralensis and Melitaea mixta). It is hypothesized that each of the remaining six haplogroups also represents a distinct species (Melitaea mauretanica, Melitaea occidentalis, Melitaea didyma, Melitaea neera, Melitaea liliputana and Melitaea turkestanica), since merging these haplogroups would result in a polyphyletic assemblage and the genetic distances between them are comparable with those found between the other six previously recognized species. PMID- 26807036 TI - Chromosome numbers in antlions (Myrmeleontidae) and owlflies (Ascalaphidae) (Insecta, Neuroptera). AB - A short review of main cytogenetic features of insects belonging to the sister neuropteran families Myrmeleontidae (antlions) and Ascalaphidae (owlflies) is presented, with a particular focus on their chromosome numbers and sex chromosome systems. Diploid male chromosome numbers are listed for 37 species, 21 genera from 9 subfamilies of the antlions as well as for seven species and five genera of the owlfly subfamily Ascalaphinae. The list includes data on five species whose karyotypes were studied in the present work. It is shown here that antlions and owlflies share a simple sex chromosome system XY/XX; a similar range of chromosome numbers, 2n = 14-26 and 2n = 18-22 respectively; and a peculiar distant pairing of sex chromosomes in male meiosis. Usually the karyotype is particularly stable within a genus but there are some exceptions in both families (in the genera Palpares and Libelloides respectively). The Myrmeleontidae and Ascalaphidae differ in their modal chromosome numbers. Most antlions exhibit 2n = 14 and 16, and Palparinae are the only subfamily characterized by higher numbers, 2n = 22, 24, and 26. The higher numbers, 2n = 20 and 22, are also found in owlflies. Since the Palparinae represent a basal phylogenetic lineage of the Myrmeleontidae, it is hypothesized that higher chromosome numbers are ancestral for antlions and were inherited from the common ancestor of Myrmeleontidae + Ascalaphidae. They were preserved in the Palparinae (Myrmeleontidae), but changed via chromosomal fusions toward lower numbers in other subfamilies. PMID- 26807037 TI - Comparative cytogenetics of Auchenorrhyncha (Hemiptera, Homoptera): a review. AB - A comprehensive review of cytogenetic features is provided for the large hemipteran suborder Auchenorrhyncha, which currently contains approximately 42,000 valid species. This review is based on the analysis of 819 species, 483 genera, and 31 families representing all presently recognized Auchenorrhyncha superfamilies, e.i. Cicadoidea (cicadas), Cercopoidea (spittle bugs), Membracoidea (leafhoppers and treehoppers), Myerslopioidea (ground-dwelling leafhoppers), and Fulgoroidea (planthoppers). History and present status of chromosome studies are described, as well as the structure of chromosomes, chromosome counts, trends and mechanisms of evolution of karyotypes and sex determining systems, their variation at different taxonomic levels and most characteristic (modal) states, occurrence of parthenogenesis, polyploidy, B chromosomes and chromosome rearrangements, and methods used for cytogenetic analysis of Auchenorrhyncha. PMID- 26807038 TI - Achiasmate male meiosis in two Cymatia species (Hemiptera, Heteroptera, Corixidae). AB - The karyotype and male meiosis, with a particular focus on the presence or absence of chiasmata between the homologs, were studied in the water boatman species Cymatia rogenhoferi (Fieber) and Cymatia coleoptrata (Fabricius) (Corixidae, Cymatiainae). It is shown that the species have 2n = 33 (28A+2m+X1X2Y) and 2n = 24 (20A+2m+XY) respectively, post-reduction of sex chromosomes, and achiasmate meiosis of an alignment type in males. Cytogenetic and some morphological diagnostic characters separating Cymatia Flor from the rest of Corixidae are discussed. PMID- 26807039 TI - Dimethylamine as a major alkyl amine species in particles and cloud water: Observations in semi-arid and coastal regions. AB - Aerosol and cloud water measurements of dimethylamine (DMA), the most abundant amine in this study, were conducted in semi-arid (Tucson, Arizona) and marine (Nucleation in California Experiment, NiCE; central coast of California) areas. In both regions, DMA exhibits a unimodal aerosol mass size distribution with a dominant peak between 0.18 and 0.56 MUm. Particulate DMA concentrations increase as a function of marine biogenic emissions, sulfate, BVOC emissions, and aerosol phase water. Such data supports biogenic sources of DMA, aminium salt formation, and partitioning of DMA to condensed phases. DMA concentrations exhibit positive correlations with various trace elements and most especially vanadium, which warrants additional investigation. Cloud water DMA levels are enhanced significantly during wildfire periods unlike particulate DMA levels, including in droplet residual particles, due to effective dissolution of DMA into cloud water and probably DMA volatilization after drop evaporation. DMA:NH+4 molar ratios peak between 0.18 and 1.0 MUm depending on the site and time of year, suggesting that DMA competes better with NH3 in those sizes in terms of reactive uptake by particles. PMID- 26807040 TI - A study of snake-like locomotion through the analysis of a flexible robot model. AB - We examine the problem of snake-like locomotion by studying a system consisting of a planar inextensible elastic rod with adjustable spontaneous curvature, which provides an internal actuation mechanism that mimics muscular action in a snake. Using a Cosserat model, we derive the equations of motion in two special cases: one in which the rod can only move along a prescribed curve, and one in which the rod is constrained to slide longitudinally without slipping laterally, but the path is not fixed a priori (free-path case). The second setting is inspired by undulatory locomotion of snakes on flat surfaces. The presence of constraints leads in both cases to non-standard boundary conditions that allow us to close and solve the equations of motion. The kinematics and dynamics of the system can be recovered from a one-dimensional equation, without any restrictive assumption on the followed trajectory or the actuation. We derive explicit formulae highlighting the role of spontaneous curvature in providing the driving force (and the steering, in the free-path case) needed for locomotion. We also provide analytical solutions for a special class of serpentine motions, which enable us to discuss the connection between observed trajectories, internal actuation and forces exchanged with the environment. PMID- 26807041 TI - Sensitivity of forces to wall transpiration in flow past an aerofoil. AB - The adjoint-based sensitivity analyses well explored in hydrodynamic stability studies are extended to calculate the sensitivity of forces acting on an aerofoil with respect to wall transpiration. The magnitude of the sensitivity quantifies the controllability of the force, and the distribution of the sensitivity represents a most effective control when the control magnitude is small enough. Since the sensitivity to streamwise control is one order smaller than that to the surface-normal one, the work is concentrated on the normal control. In direct numerical simulations of flow around a NACA0024 aerofoil, the unsteady controls are far less effective than the steady control owing to the lock-in effect. At a momentum coefficient of 0.0008 and a maximum control velocity of 3.6% of the free stream velocity, the steady surface-normal control reduces drag by 20% or enhances lift by up to 140% at Re=1000. A suction around the low-pressure region on the upper surface upstream of the separation point is found to reduce drag and enhance lift. At higher Reynolds numbers, the uncontrolled flow becomes three dimensional and the sensitivity diverges owing to the chaotic dynamics of the flow. Then the mechanism identified at lower Reynolds numbers is exploited to obtain the control, which is localized and can be generated by a limited number of actuators. The control to reduce drag or enhance lift is found to suppress unsteadiness, e.g. vortex shedding and three-dimensional developments. For example, at Re=2000 and alpha=10 degrees , the control with a momentum coefficient of 0.0001 reduces drag by 20%, enhances lift by up to 200% and leads to a steady controlled flow. PMID- 26807042 TI - Verification of cardiac mechanics software: benchmark problems and solutions for testing active and passive material behaviour. AB - Models of cardiac mechanics are increasingly used to investigate cardiac physiology. These models are characterized by a high level of complexity, including the particular anisotropic material properties of biological tissue and the actively contracting material. A large number of independent simulation codes have been developed, but a consistent way of verifying the accuracy and replicability of simulations is lacking. To aid in the verification of current and future cardiac mechanics solvers, this study provides three benchmark problems for cardiac mechanics. These benchmark problems test the ability to accurately simulate pressure-type forces that depend on the deformed objects geometry, anisotropic and spatially varying material properties similar to those seen in the left ventricle and active contractile forces. The benchmark was solved by 11 different groups to generate consensus solutions, with typical differences in higher-resolution solutions at approximately 0.5%, and consistent results between linear, quadratic and cubic finite elements as well as different approaches to simulating incompressible materials. Online tools and solutions are made available to allow these tests to be effectively used in verification of future cardiac mechanics software. PMID- 26807043 TI - Non-unions treated with bone morphogenic protein 7: introducing the quantitative measurement of human serum cytokine levels as promising tool in evaluation of adjunct non-union therapy. AB - BACKGROUND: In this study we sought to determine if application of bone morphogenic protein 7 (BMP-7) promotes physiological bone healing of non-unions and to investigate if serum cytokine analysis may serve as a promising tool in the analysis of adjunct non-union therapy. Therefore we analyzed the influence of BMP-7 application on the serum cytokine expression patterns on patients with impaired bone healing compared to patients that showed proper bone healing. METHODS: Our study involved analyzing blood samples from 208 patients with long bone fractures together with patients that subsequently developed non-unions. From this large pool, 15 patients with atrophic non-union were matched to 15 patients with atrophic non-union treated with local application of BMP-7 as well as normal bone healing. Changes in the cytokine expression patterns were monitored during the 1st, 2nd, 4th, 8th, 12th and 52nd week. The patients were followed both clinically and radiologically for the entire duration of the study. Serum cytokine expression levels of transforming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) were analyzed and compared. RESULTS: Serum expression of TGF-beta were nearly parallel in all three groups, however serum concentrations were significantly higher in patients with proper bone healing and those treated with BMP-7 than in patients with non-unions (p < 0.05). bFGF serum concentrations increased initially in patients with proper bone healing and in those treated with BMP-7. Afterwards, values decreased; bFGF serum concentrations in the BMP-7 group were significantly higher than in the other groups (p < 0.05). PDGF serum concentration levels were nearly parallel in all groups, serum concentrations were significantly higher in patients with proper bone healing and those treated with BMP-7 than in patients with non-unions (p < 0.05). CONCLUSION: Treatment with BMP-7 in patients with former non-unions led to similar cytokine expression patterns after treatment as those found in patients with proper bone healing. Our results suggest that treatment with BMP-7 promote healing of non-unions. Furthermore, quantitative measurement of serum cytokine expression is a promising tool for evaluating the effectiveness of additional non-union therapies such as adjunct application of growth factors. PMID- 26807044 TI - Exploring the influence of context and policy on health district productivity in Cambodia. AB - BACKGROUND: Cambodia has been reconstructing its economy and health sector since the end of conflict in the 1990s. There have been gains in life expectancy and increased health expenditure, but Cambodia still lags behind neighbours One factor which may contribute is the efficiency of public health services. This article aims to understand variations in efficiency and the extent to which changes in efficiency are associated with key health policies that have been introduced to strengthen access to health services over the past decade. METHODS: The analysis makes use of data envelopment analysis (DEA) to measure relative efficiency and changes in productivity and regression analysis to assess the association with the implementation of health policies. Data on 28 operational districts were obtained for 2008-11, focussing on the five provinces selected to represent a range of conditions in Cambodia. DEA was used to calculate efficiency scores assuming constant and variable returns to scale and Malmquist indices to measure productivity changes over time. This analysis was combined with qualitative findings from 17 key informant interviews and 19 in-depth interviews with managers and staff in the same provinces. RESULTS: The DEA results suggest great variation in the efficiency scores and trends of scores of public health services in the five provinces. Starting points were significantly different, but three of the five provinces have improved efficiency considerably over the period. Higher efficiency is associated with more densely populated areas. Areas with health equity funds in Special Operating Agency (SOA) and non-SOA areas are associated with higher efficiency. The same effect is not found in areas only operating voucher schemes. We find that the efficiency score increased by 0.12 the year any of the policies was introduced. CONCLUSIONS: This is the first study published on health district productivity in Cambodia. It is one of the few studies in the region to consider the impact of health policy changes on health sector efficiency. The results suggest that the recent health financing reforms have been effective, singly and in combination. This analysis could be extended nationwide and used for targeting of new initiatives. The finding of an association between recent policy interventions and improved productivity of public health services is relevant for other countries planning similar health sector reforms. PMID- 26807045 TI - Is a Bird an Apple? The Effect of Speaker Labeling Accuracy on Infants' Word Learning, Imitation, and Helping Behaviors. AB - This study examined infants' sensitivity to a speaker's verbal accuracy and whether the reliability of the speaker had an effect on their selective trust. Forty-nine 18-month-old infants were exposed to a speaker who either accurately or inaccurately labeled familiar objects. Subsequently, the speaker administered a series of tasks in which infants had an opportunity to: learn a novel word, imitate the speaker's "irrational" actions, and help the speaker obtain an out-of reach object. In contrast to infants in the accurate (reliable) condition, those in the inaccurate (unreliable) condition performed more poorly on a word-learning task and were less likely to imitate. All infants demonstrated high rates of instrumental helping behavior. These results are the first to demonstrate that infants as young as 18 months of age cannot only detect a speaker's verbal inaccuracy but also use this information to attenuate their word recognition and learning of novel actions. PMID- 26807046 TI - Perceived Discrimination and Social Relationship Functioning among Sexual Minorities: Structural Stigma as a Moderating Factor. AB - Work on structural stigma shows how public policy affects health outcomes for members of devalued groups, including sexual minorities. In the current research, structural stigma is proposed as a moderating variable that strengthens deleterious associations between perceived discrimination and social relationship functioning. Hypotheses were tested in two cross-sectional studies, including both online (N = 214; Study 1) and community (N = 94; Study 2) samples of sexual minority men and women residing throughout the United States. Structural stigma was coded from policy related to sexual minority rights within each state. Confirming hypotheses, support for the moderating role of structural stigma was found via multilevel models across studies. Specifically, associations between perceived discrimination and friendship strain, loneliness (Study 1) and familial strain (Study 2) were increased for those who resided in states with greater levels of structural stigma and attenuated for those who resided in states with lesser levels. In Study 1, these results were robust to state-level covariates (conservatism and religiosity), but conservatism emerged as a significant moderator in lieu of structural stigma in Study 2. Results are discussed in the context of the shifting landscape of public policy related to sexual minority rights within the United States. PMID- 26807047 TI - In their own words: oral histories of Medical Library Association past presidents. AB - OBJECTIVE: The purpose of this lecture was to review the development of the Medical Library Association (MLA) oral history program and to highlight the oral histories of thirty-seven past MLA presidents to identify themes of common interest and relevance to current MLA members. METHODS: The lecture focused on three main topics discussed in many of the interviews: the presidents' backgrounds and how they came to be medical librarians, how MLA developed as an organization as a reflection of the growth of medical libraries, and the presidents' predictions and advice about the future. RESULTS: MLA presidents came from varied backgrounds and locales. As MLA grew from a small, intimate group into a multifaceted organization with a professional management staff, the workload of the presidents changed in scope. One recurring theme in the presidential oral histories was the power differential between men and women in the organization and the profession. MLA presidents reminisced about notable annual meetings and praised the positive impact of the organization on members' professional and personal lives. CONCLUSIONS: The lecture concludes with recommendations to the organization to increase the availability of the oral histories by providing online access for future interviews and to pay careful attention to their long-term preservation. PMID- 26807048 TI - Scanning technology selection impacts acceptability and usefulness of image-rich content. AB - OBJECTIVE: Clinical and research usefulness of articles can depend on image quality. This study addressed whether scans of figures in black and white (B&W), grayscale, or color, or portable document format (PDF) to tagged image file format (TIFF) conversions as provided by interlibrary loan or document delivery were viewed as acceptable or useful by radiologists or pathologists. METHODS: Residency coordinators selected eighteen figures from studies from radiology, clinical pathology, and anatomic pathology journals. With original PDF controls, each figure was prepared in three or four experimental conditions: PDF conversion to TIFF, and scans from print in B&W, grayscale, and color. Twelve independent observers indicated whether they could identify the features and whether the image quality was acceptable. They also ranked all the experimental conditions of each figure in terms of usefulness. RESULTS: Of 982 assessments of 87 anatomic pathology, 83 clinical pathology, and 77 radiology images, 471 (48%) were unidentifiable. Unidentifiability of originals (4%) and conversions (10%) was low. For scans, unidentifiability ranged from 53% for color, to 74% for grayscale, to 97% for B&W. Of 987 responses about acceptability (n=405), 41% were said to be unacceptable, 97% of B&W, 66% of grayscale, 41% of color, and 1% of conversions. Hypothesized order (original, conversion, color, grayscale, B&W) matched 67% of rankings (n=215). CONCLUSIONS: PDF to TIFF conversion provided acceptable content. Color images are rarely useful in grayscale (12%) or B&W (less than 1%). Acceptability of grayscale scans of noncolor originals was 52%. Digital originals are needed for most images. Print images in color or grayscale should be scanned using those modalities. PMID- 26807049 TI - Evaluating the appropriateness of electronic information resources for learning. AB - OBJECTIVES: Current US medical students have begun to rely on electronic information repositories-such as UpToDate, AccessMedicine, and Wikipedia-for their pre-clerkship medical education. However, it is unclear whether these resources are appropriate for this level of learning due to factors involving information quality, level of evidence, and the requisite knowledgebase. This study evaluated appropriateness of electronic information resources from a novel perspective: amount of mental effort learners invest in interactions with these resources and effects of the experienced mental effort on learning. METHODS: Eighteen first-year medical students read about three unstudied diseases in the above-mentioned resources (a total of fifty-four observations). Their eye movement characteristics (i.e., fixation duration, fixation count, visit duration, and task-evoked pupillary response) were recorded and used as psychophysiological indicators of the experienced mental effort. Post reading, students' learning was assessed with multiple-choice tests. Eye metrics and test results constituted quantitative data analyzed according to the repeated Latin square design. Students' perceptions of interacting with the information resources were also collected. Participants' feedback during semi-structured interviews constituted qualitative data and was reviewed, transcribed, and open coded for emergent themes. RESULTS: Compared to AccessMedicine and Wikipedia, UpToDate was associated with significantly higher values of eye metrics, suggesting learners experienced higher mental effort. No statistically significant difference between the amount of mental effort and learning outcomes was found. More so, descriptive statistical analysis of the knowledge test scores suggested similar levels of learning regardless of the information resource used. CONCLUSIONS: Judging by the learning outcomes, all three information resources were found appropriate for learning. UpToDate, however, when used alone, may be less appropriate for first-year medical students' learning as it does not fully address their information needs and is more demanding in terms of cognitive resources invested. PMID- 26807050 TI - Rural providers' access to online resources: a randomized controlled trial. AB - OBJECTIVE: The research determined the usage and satisfaction levels with one of two point-of-care (PoC) resources among health care providers in a rural state. METHODS: In this randomized controlled trial, twenty-eight health care providers in rural areas were stratified by occupation and region, then randomized into either the DynaMed or the AccessMedicine study arm. Study participants were physicians, physician assistants, and nurses. A pre- and post-study survey measured participants' attitudes toward different information resources and their information-seeking activities. Medical student investigators provided training and technical support for participants. Data analyses consisted of analysis of variance (ANOVA), paired t tests, and Cohen's d statistic to compare pre- and post-study effects sizes. RESULTS: Participants in both the DynaMed and the AccessMedicine arms of the study reported increased satisfaction with their respective PoC resource, as expected. Participants in both arms also reported that they saved time in finding needed information. At baseline, both arms reported too little information available, which increased to "about right amounts of information" at the completion of the study. DynaMed users reported a Cohen's d increase of +1.50 compared to AccessMedicine users' reported use of 0.82. DynaMed users reported d2 satisfaction increases of 9.48 versus AccessMedicine satisfaction increases of 0.59 using a Cohen's d. CONCLUSION: Participants in the DynaMed arm of the study used this clinically oriented PoC more heavily than the users of the textbook-based AccessMedicine. In terms of user satisfaction, DynaMed users reported higher levels of satisfaction than the users of AccessMedicine. PMID- 26807051 TI - Limits of search filter development. AB - OBJECTIVE: The research attempted to develop search filters for biomedical literature databases that improve retrieval of studies of clinical relevance for the nursing and rehabilitation professions. METHODS: Diagnostic testing framework compared machine-culled and practitioner-nominated search terms with a hand tagged clinical literature database. RESULTS: We were unable to: (1) develop filters for nursing, likely because of the overlapping and expanding scope of practice for nurses in comparison with medical professionals, or (2) develop filters for rehabilitation, because of its broad scope and the profession's multifaceted understanding of "health and ability." CONCLUSIONS: We found limitations on search filter development for these health professions: nursing and rehabilitation. PMID- 26807052 TI - Performance of a mixed filter to identify relevant studies for mixed studies reviews. AB - OBJECTIVE: Mixed studies reviews include empirical studies with diverse designs. Given that identifying relevant studies for such reviews is time consuming, a mixed filter was developed. METHODS: The filter was used for six journals from three disciplines. For each journal, database records were coded "empirical" (relevant) when they mentioned a research question or objective, data collection, analysis, and results. We measured precision (proportion of retrieved documents being relevant), sensitivity (proportion of relevant documents retrieved), and specificity (proportion of nonrelevant documents not retrieved). RESULTS: Records were coded with and without the filter, and descriptive statistics were performed, suggesting the mixed filter has high sensitivity. PMID- 26807053 TI - Data literacy training needs of biomedical researchers. AB - OBJECTIVE: The research investigated topic priorities for data literacy training for biomedical researchers and staff. METHODS: An electronic survey was used to assess researchers' level of knowledge related to data literacy skills and the relevance of these skills to their work. RESULTS: Most respondents did not have any formal training in data literacy. Respondents considered most tasks highly relevant to their work but rated their expertise in tasks lower. CONCLUSION: Among this group, researchers have diverse data literacy training needs. Librarians' expertise makes them well suited to provide such training. PMID- 26807054 TI - Evaluation of popular drug information resources on clinically useful and actionable pharmacogenomic information. AB - BACKGROUND: Pharmacogenomics is the study of how genes affect a person's response to drugs. This descriptive study assessed whether popular drug information resources provide clinically useful pharmacogenomic (PGx) information. METHODS: Four resources (package inserts, Lexicomp, Micromedex 2.0, and Epocrates) were evaluated for information about twenty-seven drugs. RESULTS: There was wide variability of PGx information. Whereas Lexicomp included relevant PGx biomarker information for all 27 drugs, Epocrates did in less than 50% of the drugs. None of the resources had monographs that fully incorporated Clinical Pharmacogenomics Implementation Consortium (CPIC) recommendations in more than 30% of the drugs. CONCLUSION: Lexicomp appears to be most useful PGx drug information resource, but none of the resources are sufficient. PMID- 26807055 TI - Evolution of an academic-public library partnership. AB - A partnership to improve access to health information via an urban public library system was established in St. Louis, Missouri, in 2011. A multiyear project was outlined that included an information needs assessment, a training class for public library staff, information kiosks at library branches for delivering printed consumer health materials, and a series of health-related programming. The partnership evolved to include social service and community organizations to carry out project goals and establish a sustainable program that met the health and wellness interests of the community. PMID- 26807056 TI - Evolution of biomedical communication as reflected by the National Library of Medicine. PMID- 26807057 TI - Simple export of journal citation data to Excel using any reference manager. PMID- 26807058 TI - What is a "mapping study?". PMID- 26807059 TI - Mapping studies. PMID- 26807060 TI - Major bibliographic errors in PubMed: personal experience among 240 publications and proposed remediation process for errors. PMID- 26807061 TI - National Library of Medicine response. PMID- 26807062 TI - Proceedings, 115th Annual Meeting, Medical Library Association, Inc. Austin, TX. PMID- 26807063 TI - Measuring Ability, Speed, or Both? Challenges, Psychometric Solutions, and What Can Be Gained From Experimental Control. AB - The main challenge of ability tests relates to the difficulty of items, whereas speed tests demand that test takers complete very easy items quickly. This article proposes a conceptual framework to represent how performance depends on both between-person differences in speed and ability and the speed-ability compromise within persons. Related measurement challenges and psychometric models that have been proposed to deal with the challenges are discussed. It is argued that addressing individual differences in the speed-ability trade-off requires the control of item response times. In this way, response behavior can be captured exclusively with the response variable remedying problems in traditional measurement approaches. PMID- 26807064 TI - The Kidney Dysfunction Epidemic, Part 1: Causes. PMID- 26807065 TI - When Is a Disease a "Disease"? PMID- 26807066 TI - Harvard Team Finds 43% Reduction in Use of Health Care Services via Mind-Body Intervention ... plus more. PMID- 26807067 TI - Bernard Fox, phd: The Promise of Immunotherapy in Curing Cancer. PMID- 26807068 TI - Sixteen-year-old Female With Acute Abdominal Pain: A Case Report. AB - A 16-y-old girl presented with abdominal pain in the lower right quadrant, ranging in intensity from 2 to 10 on a visual analog scale (VAS) that prevented her from attending school. The pain was not associated with reflux, a fever, or blood in her stools. Eosinophilic esophagitis (EE) had been previously diagnosed, but treatment with a proton pump inhibitor (PPI) was not successful. The patient's medical history was significant for allergies to fruit; trees, including birch; weeds; and pollen. She had also suffered an anaphylactic reaction to a raw apple. The treatment approach commonly used for EE is suppression of inflammation with steroid therapy with short-term removal of offending foods. However, an attempt to reduce allergic bias and inflammation and treat intestinal permeability is not a part of the standard approach and may explain the high rate of relapse with the condition. Treatment included an elimination diet paired with a supplement regimen designed to reduce inflammation, support healing of the gut and reduce type 2 helper T (Th2) bias of her allergic response. As a result of treatment, the patient's severe pain episodes abated and she was thereafter able to resume attendance at school. PMID- 26807069 TI - Cannabidiol Oil for Decreasing Addictive Use of Marijuana: A Case Report. AB - This case study illustrates the use of cannabidiol (CBD) oil to decrease the addictive use of marijuana and provide anxiolytic and sleep benefits. Addiction to marijuana is a chronic, relapsing disorder, which is becoming a prevalent condition in the United States. The most abundant compound in the marijuana, which is called tetrahydrocannabinol (THC), has been widely studied and known for its psychoactive properties. The second most abundant component-CBD-has been suggested to have the medicinal effects of decreasing anxiety, improving sleep, and other neuro-protective effects. The mechanism of action for CBD has been suggested to be antagonistic to the psychoactive properties of THC in many locations within the central nervous system. Such action raises the issue of whether it might be beneficial to use CBD in isolation to facilitate withdrawal of marijuana use. The specific use of CBD for marijuana reduction has not been widely studied. The patient was a 27-y-old male who presented with a long standing diagnosis of bipolar disorder and a daily addiction to marijuana use. In the described intervention, the only change made to the patient's treatment was the addition of CBD oil with the dosage gradually decreasing from 24 to 18 mg. With use of the CBD oil, the patient reported being less anxious, as well as settling into a regular pattern of sleep. He also indicated that he had not used any marijuana since starting the CBD oil. With the decrease in the dosage to 18 mg, the patient was able to maintain his nonuse of marijuana. PMID- 26807070 TI - Kara N. Fitzgerald, nd: Case Reports-Informing the Practice of Systems Medicine. PMID- 26807071 TI - Confessions of a Narcissist. PMID- 26807072 TI - ENOX2-based early detection (ONCOblot) of asbestos-induced malignant mesothelioma 4-10 years in advance of clinical symptoms. AB - BACKGROUND: Malignant mesothelioma is an aggressive, almost uniformly fatal tumor, caused primarily by exposure to asbestos. In this study, serum presence of mesothelioma-specific protein transcript variants of ecto-nicotinamide adenine dinucleotide oxidase disulfide-thiol exchanger 2 (ENOX2), a recently identified marker of malignancy, were investigated using the ONCOblot tissue of origin cancer detection test. METHODS: Sequential serum samples collected from asbestos exposed individuals prior to the development of frank mesothelioma were assayed for ENOX2 presence by 2-D gel immunoblot analysis to determine how long in advance of clinical symptoms mesothelioma-specific ENOX2 transcript variants could be detected. RESULTS: Two mesothelioma-specific ENOX2 protein transcript variants were detected in the serum of asbestos-exposed individuals 4-10 years prior to clinical diagnosis of malignant mesothelioma (average 6.2 years). Either one or both ENOX2 protein transcript variants indicative of malignant mesothelioma were absent in 14 of 15 subjects diagnosed with benign pleural plaques either with or without accompanying asbestosis. CONCLUSIONS: In a population of asbestos-exposed subjects who eventually developed malignant mesothelioma, ENOX2 protein transcript variants characteristic of malignant mesothelioma were present in serum 4-10 years in advance of clinical symptoms. As with all biomarker studies, these observations require validation in a larger, independent cohort of patients and should include prospective as well as retrospective sampling. PMID- 26807075 TI - Patient Access to Personal Health Information: Regulation vs. Reality. AB - Patient-centered healthcare initiatives are underway to enable patients to take more responsibility for their healthcare. To do so, patients must be able to access, utilize, and share their health information. Access to health information through patient portals and other electronic means is increasing with the adoption of electronic health records (EHRs), but not all providers have EHRs or patient portals and not all information may be available electronically. Patients are expected to continue to request paper and electronic copies of their medical records. This research project was initiated to obtain up-to-date data regarding health information management (HIM) practices related to patients' access to their health information. PMID- 26807074 TI - Physicians' Outlook on ICD-10-CM/PCS and Its Effect on Their Practice. AB - BACKGROUND: The United States is one of the last countries to change from ICD-9 CM to ICD-10-CM/PCS. The compliance date for implementation of ICD-10-CM/PCS is expected to fall on October 1, 2015. OBJECTIVES: Evaluate physicians' perceptions on the change from ICD-9-CM to ICD-10-CM/PCS and its effect on their practice, determine how HIM professionals can assist in this transition, and assess what resources are needed to aid in the transition. RESULTS: Twenty physicians were asked to participate in one of three focus groups. Twelve physicians (60 percent) agreed to participate. Top concerns included electronic health record software readiness, increase in documentation specificity and time, ability of healthcare professionals to learn a new language, and inadequacy of current training methods and content. CONCLUSION: Physicians expressed that advantages of ICD-10-CM/PCS were effective data analytics and complexity of patient cases with more specific codes. Health information management professionals were touted as needed during the transition to create simple, clear specialty guides and crosswalks as well as education and training tools specific for physicians. PMID- 26807076 TI - Older Adults' Perceptions of E-Prescribing: Impact on Patient Care. AB - OBJECTIVES: To describe older adult patients' perceptions and experiences with e prescribing; and to explore the impact of e-prescribing on patient care, including patient-provider communication. METHODS: Seventy-five participants' aged 50 and older and living within one hour of Pittsburgh, Pennsylvania, completed a telephone survey that included items regarding basic demographics, general medication-taking behavior, and experiences with e-prescribing. RESULTS: A majority of participants expected e-prescriptions (84 percent) and preferred e prescriptions to paper prescriptions (81 percent). Of the 57 participants whose doctors sent their prescriptions electronically, 93 percent reported being very satisfied with their doctor and 84 percent reported being very satisfied with their pharmacist in dealing with e-prescribed medications. Participants who received e-prescriptions reported more communication regarding medication-related topics with their doctor. CONCLUSIONS: E-prescribing is generally preferred to paper prescribing, and participants who use e-prescribing are satisfied with the e-prescribing process. E-prescribing may influence patient medication-taking behaviors through increased convenience, increased patient-provider communication, and the perception of improved care compared to traditional paper prescribing. PMID- 26807077 TI - Implementing EHRs: An Exploratory Study to Examine Current Practices in Migrating Physician Practice. AB - Implementation of electronic health record (EHR) systems in physician practices is challenging and complex. In the past, physicians had little incentive to move from paper-based records. With the passage of the Health Information Technology for Economic and Clinical Health (HITECH) Act in 2009, Medicare and Medicaid incentive payments are now available for physicians who implement EHRs for meaningful use. The Office of the National Coordinator for Health Information Technology (ONC) has ample detail on clinical data needed for meaningful use in order to assess the quality of patient care. Details are lacking, however, on how much clinical data, if any, should be transferred from the old paper records during an EHR implementation project. The purpose of this exploratory study was to investigate and document the elements of longitudinal clinical data that are essential for inclusion in the EHR of physicians in a clinical practice setting, as reported by the office managers of the physicians in the study group. PMID- 26807078 TI - Evaluation of PHI Hunter in Natural Language Processing Research. AB - OBJECTIVES: We introduce and evaluate a new, easily accessible tool using a common statistical analysis and business analytics software suite, SAS, which can be programmed to remove specific protected health information (PHI) from a text document. Removal of PHI is important because the quantity of text documents used for research with natural language processing (NLP) is increasing. When using existing data for research, an investigator must remove all PHI not needed for the research to comply with human subjects' right to privacy. This process is similar, but not identical, to de-identification of a given set of documents. MATERIALS AND METHODS: PHI Hunter removes PHI from free-form text. It is a set of rules to identify and remove patterns in text. PHI Hunter was applied to 473 Department of Veterans Affairs (VA) text documents randomly drawn from a research corpus stored as unstructured text in VA files. RESULTS: PHI Hunter performed well with PHI in the form of identification numbers such as Social Security numbers, phone numbers, and medical record numbers. The most commonly missed PHI items were names and locations. Incorrect removal of information occurred with text that looked like identification numbers. DISCUSSION: PHI Hunter fills a niche role that is related to but not equal to the role of de-identification tools. It gives research staff a tool to reasonably increase patient privacy. It performs well for highly sensitive PHI categories that are rarely used in research, but still shows possible areas for improvement. More development for patterns of text and linked demographic tables from electronic health records (EHRs) would improve the program so that more precise identifiable information can be removed. CONCLUSIONS: PHI Hunter is an accessible tool that can flexibly remove PHI not needed for research. If it can be tailored to the specific data set via linked demographic tables, its performance will improve in each new document set. PMID- 26807079 TI - An Analytic Hierarchy Process-based Method to Rank the Critical Success Factors of Implementing a Pharmacy Barcode System. AB - Pharmacy barcode scanning is used to reduce errors during the medication dispensing process. However, this technology has rarely been used in hospital pharmacies in Saudi Arabia. This article describes the barriers to successful implementation of a barcode scanning system in Saudi Arabia. A literature review was conducted to identify the relevant critical success factors (CSFs) for a successful dispensing barcode system implementation. Twenty-eight pharmacists from a local hospital in Saudi Arabia were interviewed to obtain their perception of these CSFs. In this study, planning (process flow issues and training requirements), resistance (fear of change, communication issues, and negative perceptions about technology), and technology (software, hardware, and vendor support) were identified as the main barriers. The analytic hierarchy process (AHP), one of the most widely used tools for decision making in the presence of multiple criteria, was used to compare and rank these identified CSFs. The results of this study suggest that resistance barriers have a greater impact than planning and technology barriers. In particular, fear of change is the most critical factor, and training is the least critical factor. PMID- 26807080 TI - Metabolomics of chronic obstructive pulmonary disease and obstructive sleep apnea syndrome: response to Maniscalco and Motta. PMID- 26807081 TI - EXPERIENCE OF INTIMATE PARTNER VIOLENCE AS A PREDICTOR OF SEXUALLY TRANSMITTED INFECTIONS AMONG MARRIED WOMEN IN NIGERIA. AB - BACKGROUND: Intimate partner violence (IPV) is an important public health issue that is associated with adverse sexual and reproductive health outcomes including sexually transmitted infections (STIs). STIs have recently gained more recognition worldwide because they increase the risk for HIVinfection. However, there is dearth of information on the association between IPV and STIs particularly among married women in Nigeria. OBJECTIVE: To determine the association between IPV and STIs among married women in Nigeria. METHOD: This was a secondary data analysis of the 2008 Nigeria Demographic and Health Survey (NDHS) dataset. A total of 18,402 married women aged between 15 and 49 years were included. Questions about intimate partner violence were adapted from the Conflict Tactic Scale (CTS). Multiple logistic regression models were used to determine relationship between IPV and self-reported STIs. RESULTS: The prevalence of IPV among married women in Nigeria was 29.3%. Majority of the women experienced emotional violence (22.1%), 17.3% of the women experienced physical violence while the least experienced form of violence was sexual IPV (4.4%). Majority (60.1%) of the women experienced just one type of IPV, 30.0% two types, 9.9% all three types. The prevalence of self-reported sexually transmitted infections was 7.2%. Logistic regression demonstrated that after controlling for other covariates, women who experienced any form of IPV were found to be more likely to report STI than women who did not [OR 1.357 (95% CI 1.188-1.551)]. In addition, experience of physical and sexual IPV was significantly associated with history of STIs [OR 1.699 (95% CI 1.420-2.034); OR 1.414 (95% CI 1.085-1.843) respectively]. Experiencing two or more types of IPV was significantly associated with history of STIs [OR 1.759 (95% CI 1.446-2.139); OR 2.193 (95% CI 1.636 2.941) respectively]. CONCLUSION: There is a need to incorporate IPV screening and services in STI clinics. Also, it is important to screen for STIs among women who present with IPV particularly those with multiple types of violence. PMID- 26807082 TI - HOW ACCEPTABLE ARE THE PREVENTION OF MOTHER TO CHILD TRANSMISSION (PMTCT) OF HIV SERVICES AMONG PREGNANT WOMEN IN A SECONDARY HEALTH FACILITY IN IBADAN, NIGERIA? AB - BACKGROUND: Prevention of mother to child transmission of HIV (PMTCT) programme was designed to reduce mother to child transmission (MTCT) of HIV and it has been shown to be effective. However, the uptake of the services is still very low in Nigeria. OBJECTIVE: This study was designed to determine how acceptable the different services of PMTCT are to pregnant women in Ibadan, Nigeria. METHOD: Systematic random sampling was used to recruit 500 pregnant women attending antenatal clinic in a secondary health facility. Questionnaires were used to obtain data regarding socio-demographic characteristics, knowledge about MTCT of HIV and prevention, the awareness and attitude towards infant feeding options for HIV positive mothers. Data were analysed using student's t test and Chi-square test with p set at 0.05. RESULTS: Mean age of respondents was 27.4+/-6.1years. Most known routes of MTCT of HIV were during pregnancy (86.0%) and from breastfeeding (86.0%). More than 80% knew that having good antenatal care, appropriate supervised delivery, taking antiretroviral drugs and not breast feeding a baby are ways of PMTCT. About two thirds had a positive attitude towards HIV testing and counselling (HTC). Only 18.4% were aware of the exclusive breast feeding option for feeding infants of HIV positive mothers while 52.2% would not comply if asked not to breast feed. Women aged 35 years and above had better attitude towards non breast feeding. CONCLUSION: Intensified health education on the importance of HTC and promotion of exclusive breast feeding for infants of HIV positive mothers is recommended. PMID- 26807083 TI - TIME OF PRESENTATION OF STROKE PATIENTS FOR CT IMAGING IN A NIGERIAN TERTIARY HOSPITAL. AB - BACKGROUND: Neuroimaging is the cornerstone for guiding thrombolytic and interventional therapy for stroke. Beneficial outcome can only be obtained within a rather short time of less than 3-4.5 hours of symptom onset. Challenges in developing countries like Nigeria often lead to delayed presentation of stroke patients in hospitals. We sought to study the time and pattern of presentation of stroke patients for CT imaging in a Nigerian tertiary hospital. METHODS: Of the 271 stroke patients who had cranial CT between 2008 and 2010, eighty-three (30.6%) with full retrievable CT records, were included in this study. They were categorized into six time groups cross-tabulated with their CT findings. RESULTS: Forty-two patients (50.6%) had cerebral infarction while 23 (27.7%) had haemorrhagic stroke. However, 18 (21.7%) patients had apparently normal CT findings. The mean presentation time for CT imaging was 70 hours (SD +/-94 hours). Only 31% of all stroke patients presented for CT imaging within 12 hours, and none, within 3 hours. Forty-six percent did not present within 24 hours of symptom onset. Significantly more patients with ischemic stroke (72.3%) than hemorrhagic stroke (27.7%) presented after 12 hours of ictus (X(2) = 4.027 d=1, P =0.045). Age (X(2)=0.008, P =0.931) and gender (X(2)1.742, d=1,P =0.187) had no statistically significant relationship with the time of presentation for CT imaging. CONCLUSION: None of our patients met the time criteria for thrombolytic therapy. Ischemic stroke patients presented for imaging later than patients with intracerebral haemorrhage. There is a need to increase the awareness regarding early recognition, presentation and diagnosis of stroke for timely intervention in Nigeria. PMID- 26807084 TI - BLOOD TRANSFUSION REQUIREMENT DURING CAESAREAN DELIVERY: RISK FACTORS. AB - BACKGROUND: Group specific blood is often cross-matched ready for all patients scheduled for caesarean section in anticipation of haemorrhage during the surgery. This study was conducted to determine the risk factors for blood transfusion during anaesthesia for caesarean section. METHODS: This was a prospective cross-sectional study. A total of 706 pregnant patients scheduled for emergency or elective Caesarean section at the University College Hospital, Ibadan, Nigeria between March and August 2011 were recruited. Participants were followed-up from the date of delivery till the end point of the study which could fall into either of the following conditions: satisfactory post-operative clinical status up to 48 hours post-delivery or death. Transfusion rate was determined and Chi-square test was used to determine if there exist an association between blood transfusion status and preoperative haematocrit level, years of experience of obstetrician, indication for Caesarean Section(CS), CS type (primary or repeat) and HIV status. RESULTS: Transfusion rate was 9.1 %; variables found to be significantly associated with blood transfusion were; preoperative haematocrit less than 26%, increasing parity, years of experience of resident obstetrician, indication for CS (bleeding or not bleeding) and estimated blood loss. Being HIV positive does not increase the need for blood transfusion. CONCLUSION: Preoperative anaemia, increasing parity and severe blood loss at surgery significantly contribute to the requirement for blood transfusion in patients undergoing caesarean section. PMID- 26807085 TI - BARRIERS TO AN EFFECTIVE DIABETIC RETINOPATHY SERVICE IN IBADAN, NIGERIA (SUB SAHARAN AFRICA) - A PILOT QUALITATIVE STUDY. AB - BACKGROUND: Diabetic retinopathy is an increasing cause of blindness. The prevalence of retinopathy in hospital attending diabetics in Ibadan is reported to be 42 %. This study assessed the barriers identified by patients and service providers to delivering good services for diabetic retinopathy in Ibadan, Nigeria, Sub-Saharan Africa. METHODS: A qualitative survey using non participatory observation, in-depth interviews (patients and healthcare providers), and focus group discussion for diabetic patients in the eye clinic in University College Hospital, Ibadan was done. Semistructured interview and topic guides were used to evaluate the barriers to effective service. The participants were selected using a non-probability, purposive sampling strategy. Twenty participants were involved in the pilot study. There were ten in-depth interviews of patients and two focus group discussions of patients (3 in each group). Four healthcare providers were interviewed (a retinal surgeon, a senior registrar, an endocrinologist and a public health nurse). RESULTS: Lack of awareness that diabetes causes irreversible blindness was identified as a major barrier by both patients and providers. Cost of treatment of diabetes and treatment of retinopathy was also an important barrier. The long waiting time before consultation, staff attitudes to patients and appointment scheduling problems deterred patients from using the service. CONCLUSIONS: More diabetic patients can be encouraged to use eye service by providing more detailed information/counselling and making clinic attendance less costly and more convenient. PMID- 26807086 TI - ADDICTION OR PSEUDOADDICTION IN SICKLE CELL DISEASE PATIENTS: TIME TO DECIDE - A CASE SERIES. AB - OBJECTIVE: The objective of this report is to highlight the background factors associated with opioid abuse among Sickle Cell Disease (SCD) patients. PATIENTS: Eleven patients aged 13-53 years (mean, 26.1yrs) which included six female and five male were seen in the last six year at a tertiary health facility. The modes of abuse ranged from obtaining analgesic prescription from multiple sources, injecting analgesics and sharing analgesics between patients in the hospital. RESULTS: Five female had either avascular necrosis of the femoral head or pathological fracture secondary to chronic osteomyelitis, so were classified as pseudoaddiction while five male and one female without any identifiable cause of chronic pain were adjudged to be addicted to opioids. The role of a dysfunctional family background in the response of SCD patients to pain treatment and substance abuse is highlighted. CONCLUSION: These cases reveal drug abuse as an emerging or understudied problem among SCD patients and its association with chronic pain in some patients. It is therefore necessary for pain physicians and SCD experts to address the use of opioid in chronic sickle cell pain and provide alternatives and a suitable guideline for their use. PMID- 26807087 TI - FIRST REPORTS OF CLINICAL PHARMACOKINETICS IN NIGERIA. AB - The German Friedrich Hartmut Dost (1910-1985) introduced the word Pharmacokinetics. Clinical pharmacokinetics is the direct application of knowledge regarding a drug's pharmacokinetics to a therapeutic situation in an individual or a population. It is the basis of therapeutic drug monitoring with the ultimate goal of keeping drugs safe. This branch of pharmacology has become the most relevant to the sub-specialty of clinical pharmacology. First reports of Clinical Pharmacokinetics in Nigeria can be credited to two gifted Nigerians, Prof Ayodele O. Iyun and Prof Lateef A. Salako, both of whom were affiliated to the great institutions- University of Ibadan (UI) and the Teaching Hospital, University College Hospital (UCH). Prof A.O Iyun was Nigeria's first home-trained Clinical Pharmacologist, while Prof L.A. Salako played a most significant role in the creation of the Department of Clinical Pharmacology, UCH. This edition of the Chronicles highlights a few of the first reports of this exciting branch of pharmacology in Nigeria. This historical review is based on publications listed on the United States National Library of Medicine database (PUBMED). PMID- 26807088 TI - Use of sensory substitution devices as a model system for investigating cross modal neuroplasticity in humans. PMID- 26807089 TI - Studying neurological disorders using induced pluripotent stem cells and optogenetics. PMID- 26807090 TI - Efficacy of glucagon-like peptide-1 mimetics for neural regeneration. PMID- 26807091 TI - VEGF in the nervous system: an important target for research in neurodevelopmental and regenerative medicine. PMID- 26807092 TI - Intracellular sorting pathways of the amyloid precursor protein provide novel neuroprotective strategies. PMID- 26807093 TI - Brain protein oxidation: what does it reflect? PMID- 26807094 TI - Animal model of repetitive mild traumatic brain injury for human traumatic axonal injury and chronic traumatic encephalopathy. PMID- 26807095 TI - Immunization with Cop-1 promotes neuroprotection and neurogenesis after ischemic stroke. PMID- 26807096 TI - Who is who after spinal cord injury and repair? Can the brain stem descending motor pathways take control of skilled hand motor function? PMID- 26807097 TI - Propriospinal interneurons in the spotlight for anatomical and functional recovery after spinal cord injury. PMID- 26807098 TI - Sensory regeneration in dorsal root avulsion. PMID- 26807099 TI - Compliant semiconductor scaffolds: building blocks for advanced neural interfaces. PMID- 26807100 TI - Novel approaches for the development of peripheral nerve regenerative therapies. PMID- 26807101 TI - pFTAA: a high affinity oligothiophene probe that detects filamentous tau in vivo and in cultured neurons. PMID- 26807102 TI - A role for mitogen-activated protein kinase phosphatase 1 (MKP1) in neural cell development and survival. PMID- 26807103 TI - Antiglycative activity of sulforaphane: a new avenue to counteract neurodegeneration? PMID- 26807104 TI - The neuroprotective and regenerative potential of parkin and GDNF/Ret signaling in the midbrain dopaminergic system. PMID- 26807105 TI - Cognitive training in neurodegenerative diseases: a way to boost neuroprotective molecules? PMID- 26807106 TI - Polyphenols for the prevention and treatment of dementia diseases. PMID- 26807107 TI - Perspectives on neuroreparative therapies for treating multiple sclerosis. PMID- 26807108 TI - Chemotactic signaling and beyond: link between interleukin-16 and axonal degeneration in multiple sclerosis. PMID- 26807109 TI - Fetal alcohol spectrum disorder: molecular insights into neural damage reduction. PMID- 26807110 TI - Two sides of the same coin: tyrosine kinase inhibition in cancer and neurodegeneration. PMID- 26807111 TI - Physiotherapeutic techniques used in the management of patients with peripheral nerve injuries. PMID- 26807112 TI - Factors influencing the spinal motoneurons in development. AB - The development of the spinal cord needs a concerted interaction of transcription factors activating diverse genes and signals from outside acting on the specification of the different cells. Signals have to act on the segments of the embryo as well as on the cranial-caudal axis and the dorso-ventral axis. Additionally the axons of the motoneurons have to cross the central nervous system barrier to connect to the periphery. Intensive anatomical studies have been followed by molecular characterization of the different subsets of transcription factors that are expressed by cells of the developing spinal cord. Here, intensive studies for the most important appearing cells, the motoneurons, have resulted in a good knowledge on the expression patterns of these proteins. Nonetheless motoneurons are by far not the only important cells and the concert activity of all cells besides them is necessary for the correct function and integrity of motoneurons within the spinal cord. This article will briefly summarize the different aspects on spinal cord development and focuses on the differentiation as well as the functionalization of motoneurons. PMID- 26807115 TI - Correction: Potential of the use of an antioxidant compound to promote peripheral nerve regeneration after injury. AB - [This corrects the article on p. 1063 in vol. 10, PMID: 26330825.]. PMID- 26807113 TI - Repair, protection and regeneration of peripheral nerve injury. PMID- 26807114 TI - MicroRNAs: a novel promising therapeutic target for cerebral ischemia/reperfusion injury? AB - To determine the molecular mechanism of cerebral ischemia/reperfusion injury, we examined the microRNA (miRNA) expression profile in rat cortex after focal cerebral ischemia/reperfusion injury using miRNA microarrays and bioinformatic tools to systematically analyze Gene Ontology (GO) function classifications, as well as the signaling pathways of genes targeted by these differentially expressed miRNAs. Our results show significantly changed miRNA expression profiles in the reperfusion period after focal cerebral ischemia, with a total of 15 miRNAs up-regulated and 44 miRNAs down-regulated. Target genes of these differentially expressed miRNAs were mainly involved in metabolic and cellular processes, which were identified as hub nodes of a miRNA-GO-network. The most correlated pathways included D-glutamine and D-glutamate metabolism, the renin angiotensin system, peroxisomes, the PPAR signaling pathway, SNARE interactions in vesicular transport, and the calcium signaling pathway. Our study suggests that miRNAs play an important role in the pathological process of cerebral ischemia/reperfusion injury. Understanding miRNA expression and function may shed light on the molecular mechanism of cerebral ischemia/reperfusion injury. PMID- 26807116 TI - Correlating interleukin-10 promoter gene polymorphisms with human cerebral infarction onset. AB - Evidence suggests that interleukin-10 (IL-10) deficiency exacerbates inflammation and worsens the outcome of brain ischemia. In view of the critical role of the single nucleotide polymorphic sites -1082 (A/G) and -819 (C/T) in the promoter region of the IL-10 gene, we hypothesized that they are associated with cerebral infarction morbidity in the Chinese Han population. We genotyped these allelic gene polymorphisms by amplification refractory mutation system-polymerase chain reaction methods in 181 patients with cerebral infarction (cerebral infarction group) and 115 healthy subjects (control group). We identified significant differences in genotype distribution and allele frequency of the IL-10-1082 A/G allele between cerebral infarction and control groups (chi (2) = 6.643, P = 0.010). The IL-10-1082 A allele frequency was significantly higher in the cerebral infarction group (92.3%) than in the control group (86.1%) (P = 0.015). Moreover, cerebral infarction risk of the AA genotype was 2-fold higher than with the AG genotype (OR = 2.031, 95%CI: 1.134-3.637). In addition, AA genotype together with hypertension was the independent risk factor of cerebral infarction (OR = 2.073, 95%CI: 1.278-3.364). No statistical difference in genotype distribution or allele frequency of IL-10-819 C/T was found between cerebral infarction and control groups (P > 0.05). These findings suggest that the IL-10 1082 A/G gene polymorphism is involved in cerebral infarction, and increased A allele frequency is closely associated with occurrence of cerebral infarction. PMID- 26807118 TI - Leuprolide acetate induces structural and functional recovery of injured spinal cord in rats. AB - Gonadotropin-releasing hormone (GnRH) and its synthetic analog leuprolide acetate, a GnRH agonist, have neurotrophic properties. This study was designed to determine whether administration of leuprolide acetate can improve locomotor behavior, gait, micturition reflex, spinal cord morphology and the amount of microglia in the lesion epicenter after spinal cord injury in rats. Rats with spinal cord compression injury were administered leuprolide acetate or saline solution for 5 weeks. At the 5(th) week, leuprolide acetate-treated rats showed locomotor activity recovery by 38%, had improvement in kinematic gait and exhibited voiding reflex recovery by 60%, as compared with the 1(st) week. By contrast, saline solution-treated rats showed locomotor activity recovery only by 7%, but voiding reflex did not recover. More importantly, leuprolide acetate treatment reduced microglial immunological reaction and induced a trend towards greater area of white and gray matter in the spinal cord. Therefore, leuprolide acetate has great potential to repair spinal cord injury. PMID- 26807117 TI - Lentivirus-mediated Persephin over-expression in Parkinson's disease rats. AB - Persephin, together with glial cell line-derived neurotrophic factor and neurturin, has a neurotrophic effect and promotes the survival of motor neurons cultured in vitro. In this study, dopaminergic neurons in the substantia nigra of rats were transfected with the Persephin gene. One week later 6-hydroxydopamine was injected into the anterior medial bundle to establish a Parkinson's disease model in the rats. Results found that the number of dopaminergic neurons in the substantia nigra increased, tyrosine hydroxylase expression was upregulated and concentrations of dopamine and its metabolites in corpus striatum were increased after pretreatment with Persephin gene. In addition, the rotating effect of the induced Parkinson's disease rats was much less in the group pretreated with the Persephin gene. Persephin has a neuroprotective effect on the 6-hydroxydopamine induced Parkinson's disease through protecting dopaminergic neurons. PMID- 26807119 TI - Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia? AB - The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 ug) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia. PMID- 26807120 TI - Serine-threonine protein kinase activation may be an effective target for reducing neuronal apoptosis after spinal cord injury. AB - The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, including extracellular signal-regulated kinase (ERK), serine-threonine protein kinase (Akt) and c-Jun N-terminal kinase (JNK) signaling pathways. We established a rat model of acute spinal cord injury by inserting a catheter balloon in the left subclavian artery for 25 minutes. Rat models exhibited notable hindlimb dysfunction. Apoptotic cells were abundant in the anterior horn and central canal of the spinal cord. The number of apoptotic neurons was highest 48 hours post injury. The expression of phosphorylated Akt (p-Akt) and phosphorylated ERK (p ERK) increased immediately after reperfusion, peaked at 4 hours (p-Akt) or 2 hours (p-ERK), decreased at 12 hours, and then increased at 24 hours. Phosphorylated JNK expression reduced after reperfusion, increased at 12 hours to near normal levels, and then showed a downward trend at 24 hours. Pearson linear correlation analysis also demonstrated that the number of apoptotic cells negatively correlated with p-Akt expression. These findings suggest that activation of Akt may be a key contributing factor in the delay of neuronal apoptosis after spinal cord ischemia, particularly at the stage of reperfusion, and thus may be a target for neuronal protection and reduction of neuronal apoptosis after spinal cord injury. PMID- 26807121 TI - Combination of fasudil and celecoxib promotes the recovery of injured spinal cord in rats better than celecoxib or fasudil alone. AB - Resistance mechanisms of rho-associated kinase (ROCK) inhibitors are associated with the enhanced expression of cyclooxygenase-2 (COX-2). The therapeutic effects of ROCK on nervous system diseases might be enhanced by COX-2 inhibitors. This study investigated the synergistic effect of the combined use of the ROCK inhibitor fasudil and a COX-2 inhibitor celecoxib on spinal cord injury in a rat model established by transecting the right half of the spinal cord at T11. Rat models were orally administrated with celecoxib (20 mg/kg) and/or intramuscularly with fasudil (10 mg/kg) for 2 weeks. Results demonstrated that the combined use of celecoxib and fasudil significantly decreased COX-2 and Rho kinase II expression surrounding the lesion site in rats with spinal cord injury, improved the pathomorphology of the injured spinal cord, and promoted the recovery of motor function. Moreover, the effects of the drug combination were better than celecoxib or fasudil alone. This study demonstrated that the combined use of fasudil and celecoxib synergistically enhanced the functional recovery of injured spinal cord in rats. PMID- 26807122 TI - Autologous mesenchymal stem cells applied on the pressure ulcers had produced a surprising outcome in a severe case of neuromyelitis optica. AB - Recent studies provided evidence that mesenchymal stem cells (MSCs) have regenerative potential in cutaneous repair and profound immunomodulatory properties making them a candidate for therapy of neuroimmunologic diseases. Neuromyelitis optica (NMO) is an autoimmune, demyelinating central nervous system disorder characterized by a longitudinally extensive spinal cord lesion. A 46 year-old male diagnosed with NMO had relapses with paraplegia despite treatment and developed two stage IV pressure ulcers (PUs) on his legs. The patient consented for local application of autologous MSCs on PUs. MSCs isolated from the patient's bone marrow aspirate were multiplied in vitro during three passages and embedded in a tridimensional collagen-rich matrix which was applied on the PUs. Eight days after MSCs application the patient showed a progressive healing of PUs and improvement of disability. Two months later the patient was able to walk 20 m with bilateral assistance and one year later he started to walk without assistance. For 76 months the patient had no relapse and no adverse event was reported. The original method of local application of autologous BM-MSCs contributed to healing of PUs. For 6 years the patient was free of relapses and showed an improvement of disability. The association of cutaneous repair, sustained remission of NMO and improvement of disability might be explained by a promotion/optimization of recovery mechanisms in the central nervous system even if alternative hypothesis should be considered. Further studies are needed to assess the safety and efficacy of mesenchymal stem cells in NMO treatment. PMID- 26807123 TI - Neuroprotective effects of ultrasound-guided nerve growth factor injections after sciatic nerve injury. AB - Nerve growth factor (NGF) plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half life; it is therefore important to identify an effective mode of administration. High-frequency ultrasound (HFU) is increasingly used in the clinic for high resolution visualization of tissues, and has been proposed as a method for identifying and evaluating peripheral nerve damage after injury. In addition, HFU is widely used for guiding needle placement when administering drugs to a specific site. We hypothesized that HFU guiding would optimize the neuroprotective effects of NGF on sciatic nerve injury in the rabbit. We performed behavioral, ultrasound, electrophysiological, histological, and immunohistochemical evaluation of HFU-guided NGF injections administered immediately after injury, or 14 days later, and compared this mode of administration with intramuscular NGF injections. Across all assessments, HFU guided NGF injections gave consistently better outcomes than intramuscular NGF injections administered immediately or 14 days after injury, with immediate treatment also yielding better structural and functional results than when the treatment was delayed by 14 days. Our findings indicate that NGF should be administered as early as possible after peripheral nerve injury, and highlight the striking neuroprotective effects of HFU-guided NGF injections on peripheral nerve injury compared with intramuscular administration. PMID- 26807124 TI - Single injection of platelet-rich plasma as a novel treatment of carpal tunnel syndrome. AB - Both in vitro and in vivo experiments have confirmed that platelet-rich plasma has therapeutic effects on many neuropathies, but its effects on carpal tunnel syndrome remain poorly understood. We aimed to investigate whether single injection of platelet-rich plasma can improve the clinical symptoms of carpal tunnel syndrome. Fourteen patients presenting with median nerve injury who had suffered from mild carpal tunnel syndrome for over 3 months were included in this study. Under ultrasound guidance, 1-2 mL of platelet-rich plasma was injected into the region around the median nerve at the proximal edge of the carpal tunnel. At 1 month after single injection of platelet-rich plasma, Visual Analogue Scale results showed that pain almost disappeared in eight patients and it was obviously alleviated in three patients. Simultaneously, the disabilities of the arm, shoulder and hand questionnaire showed that upper limb function was obviously improved. In addition, no ultrasonographic manifestation of the carpal tunnel syndrome was found in five patients during ultrasonographic measurement of the width of the median nerve. During 3-month follow-up, the pain was not greatly alleviated in three patients. These findings show very encouraging mid-term outcomes regarding use of platelet-rich plasma for the treatment of carpal tunnel syndrome. PMID- 26807125 TI - Changes in lumbosacral spinal nerve roots on diffusion tensor imaging in spinal stenosis. AB - Lumbosacral degenerative disc disease is a common cause of lower back and leg pain. Conventional T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) scans are commonly used to image spinal cord degeneration. However, these modalities are unable to image the entire lumbosacral spinal nerve roots. Thus, in the present study, we assessed the potential of diffusion tensor imaging (DTI) for quantitative assessment of compressed lumbosacral spinal nerve roots. Subjects were 20 young healthy volunteers and 31 patients with lumbosacral stenosis. T2WI showed that the residual dural sac area was less than two-thirds that of the corresponding normal area in patients from L3 to S1 stenosis. On T1WI and T2WI, 74 lumbosacral spinal nerve roots from 31 patients showed compression changes. DTI showed thinning and distortion in 36 lumbosacral spinal nerve roots (49%) and abruption in 17 lumbosacral spinal nerve roots (23%). Moreover, fractional anisotropy values were reduced in the lumbosacral spinal nerve roots of patients with lumbosacral stenosis. These findings suggest that DTI can objectively and quantitatively evaluate the severity of lumbosacral spinal nerve root compression. PMID- 26807126 TI - Endogenous neurotrophin-3 promotes neuronal sprouting from dorsal root ganglia. AB - In the present study, we investigated the role of endogenous neurotrophin-3 in nerve terminal sprouting 2 months after spinal cord dorsal root rhizotomy. The left L1-5 and L7-S2 dorsal root ganglia in adult cats were exposed and removed, preserving the L6 dorsal root ganglia. Neurotrophin-3 was mainly expressed in large neurons in the dorsal root ganglia and in some neurons in spinal lamina II. Two months after rhizotomy, the number of neurotrophin-3-positive neurons in the spared dorsal root ganglia and the density of neurite sprouts emerging from these ganglia were increased. Intraperitoneal injection of an antibody against neurotrophin-3 decreased the density of neurite sprouts. These findings suggest that endogenous neurotrophin-3 is involved in spinal cord plasticity and regeneration, and that it promotes axonal sprouting from the dorsal root ganglia after spinal cord dorsal root rhizotomy. PMID- 26807127 TI - Mechanical properties of nerve roots and rami radiculares isolated from fresh pig spinal cords. AB - No reports have described experiments designed to determine the strength characteristics of spinal nerve roots and rami radiculares for the purpose of explaining the complexity of symptoms of medullary cone lesions and cauda equina syndrome. In this study, to explain the pathogenesis of cauda equina syndrome, monoaxial tensile tests were performed to determine the strength characteristics of spinal nerve roots and rami radiculares, and analysis was conducted to evaluate the stress-strain relationship and strength characteristics. Using the same tensile test device, the nerve root and ramus radiculares isolated from the spinal cords of pigs were subjected to the tensile test and stress relaxation test at load strain rates of 0.1, 1, 10, and 100 s(-1) under identical settings. The tensile strength of the nerve root was not rate dependent, while the ramus radiculares tensile strength tended to decrease as the strain rate increased. These findings provide important insights into cauda equina symptoms, radiculopathy, and clinical symptoms of the medullary cone. PMID- 26807128 TI - Injury of corticoreticular pathway and corticospinal tract caused by ventriculoperitoneal shunting. PMID- 26807129 TI - Severe bilateral anterior cingulum injury in patients with mild traumatic brain injury. PMID- 26807130 TI - Susceptibility weighted imaging in the evaluation of hemorrhagic diffuse axonal injury. PMID- 26807133 TI - Bayesian estimation of the discrete coefficient of determination. AB - The discrete coefficient of determination (CoD) measures the nonlinear interaction between discrete predictor and target variables and has had far reaching applications in Genomic Signal Processing. Previous work has addressed the inference of the discrete CoD using classical parametric and nonparametric approaches. In this paper, we introduce a Bayesian framework for the inference of the discrete CoD. We derive analytically the optimal minimum mean-square error (MMSE) CoD estimator, as well as a CoD estimator based on the Optimal Bayesian Predictor (OBP). For the latter estimator, exact expressions for its bias, variance, and root-mean-square (RMS) are given. The accuracy of both Bayesian CoD estimators with non-informative and informative priors, under fixed or random parameters, is studied via analytical and numerical approaches. We also demonstrate the application of the proposed Bayesian approach in the inference of gene regulatory networks, using gene-expression data from a previously published study on metastatic melanoma. PMID- 26807131 TI - Targeting brain microvascular endothelial cells: a therapeutic approach to neuroprotection against stroke. AB - Brain microvascular endothelial cells form the interface between nervous tissue and circulating blood, and regulate central nervous system homeostasis. Brain microvascular endothelial cells differ from peripheral endothelial cells with regards expression of specific ion transporters and receptors, and contain fewer fenestrations and pinocytotic vesicles. Brain microvascular endothelial cells also synthesize several factors that influence blood vessel function. This review describes the morphological characteristics and functions of brain microvascular endothelial cells, and summarizes current knowledge regarding changes in brain microvascular endothelial cells during stroke progression and therapies. Future studies should focus on identifying mechanisms underlying such changes and developing possible neuroprotective therapeutic interventions. PMID- 26807132 TI - The role of the Rho/ROCK signaling pathway in inhibiting axonal regeneration in the central nervous system. AB - The Rho/Rho-associated coiled-coil containing protein kinase (Rho/ROCK) pathway is a major signaling pathway in the central nervous system, transducing inhibitory signals to block regeneration. After central nervous system damage, the main cause of impaired regeneration is the presence of factors that strongly inhibit regeneration in the surrounding microenvironment. These factors signal through the Rho/ROCK signaling pathway to inhibit regeneration. Therefore, a thorough understanding of the Rho/ROCK signaling pathway is crucial for advancing studies on regeneration and repair of the injured central nervous system. PMID- 26807134 TI - Anaphylaxis following a transvaginal ultrasound. AB - Polyethylene glycol is a ubiquitous, water-soluble, organic compound found in a wide variety of commercially available products. While generally a benign substance, in rare instances, it can induce hypersensitivity reactions. Herein, we describe a case of anaphylaxis to polyethylene glycol-containing lubricating gel used for a transvaginal ultrasound. This case highlights the importance of early recognition of a rare cause of anaphylaxis that may occur in the health care setting. It is of particular importance given the widespread use of similar lubricating materials in multiple practice settings for the use of internal examinations and ultrasonography. PMID- 26807136 TI - Association between allergic rhinitis and metabolic conditions: a nationwide survey in Korea. AB - BACKGROUND: Accumulating evidence indicates a strong correlation between allergic disease and cardiovascular risks. In spite of this, the data concerning the association between allergic rhinitis (AR) and cardiovascular risks is sparse and conflicting. This study aimed to investigate the association between AR prevalence and metabolic syndrome (MetS) in a large-scale, population-based survey, while considering the relevant risk factors. METHODS: A nationwide cross sectional study was conducted based on data from 30,590 subjects aged 19 years and older, from the Korean National Health and Nutrition Survey 2007-2013. The odds ratios (ORs) and 95 % confidence intervals (CIs) of AR prevalence, based on MetS status and the presence of any MetS component, were calculated using multiple logistic regression analyses. RESULTS: Regarding the characteristics of patients with AR and/or MetS, some variables had significant associations with disease in inverse directions for AR and MetS. Multivariate logistic analysis, with adjustments for demographic variables and health habits, indicated that AR prevalence was significantly lower in subjects with MetS (OR 0.84; 95 % CI 0.76 0.93), high blood pressure (OR 0.85; 95 % CI 0.77-0.94), or impaired fasting glucose (OR 0.81; 95 % CI 0.73-0.89). Furthermore, high blood pressure and impaired fasting glucose were significant predictors for reduced AR prevalence, independently of other MetS components. CONCLUSION: In this population, AR was diagnosed less frequently in subjects with metabolic conditions. Well-designed prospective studies allowing for medical service utilization and collaborative basic research are warranted to elucidate the mechanism responsible for this inverse relationship. PMID- 26807135 TI - The role of cytokines in the pathogenesis and staging of Trypanosoma brucei rhodesiense sleeping sickness. AB - Human African trypanosomiasis due to Trypanosoma brucei rhodesiense is invariably fatal if untreated with up to 12.3 million people at a risk of developing the disease in Sub-Saharan Africa. The disease is characterized by a wide spectrum of clinical presentation coupled with differences in disease progression and severity. While the factors determining this varied response have not been clearly characterized, inflammatory cytokines have been partially implicated as key players. In this review, we consolidate available literature on the role of specific cytokines in the pathogenesis of T. b. rhodesiense sleeping sickness and further discuss their potential as stage biomarkers. Such information would guide upcoming research on the immunology of sleeping sickness and further assist in the selection and evaluation of cytokines as disease stage or diagnostic biomarkers. PMID- 26807137 TI - Randomised trials for the Fitbit generation. AB - Data from activity trackers and mobile phones can be used to craft personalised health interventions. But measuring the efficacy of these "treatments" requires a rethink of the traditional randomised trial. PMID- 26807138 TI - Burnout among young physicians and its association with physicians' wishes to leave: results of a survey in Saxony, Germany. AB - BACKGROUND: Concerns about burnout, and its consequences, among German physicians are rising. However, data on burnout among German physicians are scarce. Also, a suspected association between burnout and German physicians' wishes to leave remains to be studied. Therefore, the extent of burnout, and the association between burnout and wishes to leave clinical practice or to go abroad for clinical work was studied in a sample of young physicians in Saxony. METHODS: In a cross-sectional survey, all physicians <=40 years and registered with the State Chamber of Physicians of Saxony, Germany (n = 5956) received a paper-pencil questionnaire inquiring about socio-demographics, job satisfaction, and wishes to leave clinical practice or to go abroad for clinical work. Response rate was 40 % (n = 2357). Burnout was measured with the German version of the Maslach Burnout Inventory - Human Services Survey (MBI) consisting of the subscales emotional exhaustion (feeling emotionally drained), depersonalization (feelings of cynicsm) and personal accomplishment (feelings of personal achievement in job). Variables associated with burnout, and the association between burnout and wishes to leave were assessed in multivariate logistic regression analyses. RESULTS: For emotional exhaustion participants reached a mean of 21.3 [standard deviation = 9.74], for depersonalization a mean of 9.9 [5.92], and for personal accomplishment a mean of 36.3 [6.77]. Men exhibited significantly higher depersonalization than women (11.3 [6.11] versus 9 [5.62], p < 0.001). Eleven percent of participants showed a high degree of burnout on all subscales, while 35 % did not show a high degree of burnout on any subscale. Confirming that one would become a physician again, and higher satisfaction with the components "work environment" and "humaneness", were associated with a lower chance for a high degree of burnout on all subscales. Higher emotional exhaustion and lower personal accomplishment were associated with an increased chance of wishing to leave clinical practice. Higher emotional exhaustion and higher depersonalization were associated with an increased chance of wishing to go abroad for clinical work. CONCLUSIONS: Preventing physician burnout may not only benefit the affected individual. It may also benefit the health care system by potentially preventing physicians from leaving clinical practice or from going abroad for clinical work. PMID- 26807139 TI - A novel method to characterize silica bodies in grasses. AB - BACKGROUND: The deposition of silicon into epidermal cells of grass species is thought to be an important mechanism that plants use as a defense against pests and environmental stresses. There are a number of techniques available to study the size, density and distribution pattern of silica bodies in grass leaves. However, none of those techniques can provide a high-throughput analysis, especially for a great number of samples. RESULTS: We developed a method utilizing the autofluorescence of silica bodies to investigate their size and distribution, along with the number of carbon inclusions within the silica bodies of perennial grass species Koeleria macrantha. Fluorescence images were analyzed by image software Adobe Photoshop CS5 or ImageJ that remarkably facilitated the quantification of silica bodies in the dry ash. We observed three types of silica bodies or silica body related mineral structures. Silica bodies were detected on both abaxial and adaxial epidermis of K. macrantha leaves, although their sizes, density, and distribution patterns were different. No auto-fluorescence was detected from carbon inclusions. CONCLUSIONS: The combination of fluorescence microscopy and image processing software displayed efficient utilization in the identification and quantification of silica bodies in K. macrantha leaf tissues, which should applicable to biological, ecological and geological studies of grasses including forage, turf grasses and cereal crops. PMID- 26807140 TI - Inoculation insensitive promoters for cell type enriched gene expression in legume roots and nodules. AB - BACKGROUND: Establishment and maintenance of mutualistic plant-microbial interactions in the rhizosphere and within plant roots involve several root cell types. The processes of host-microbe recognition and infection require complex signal exchange and activation of downstream responses. These molecular events coordinate host responses across root cell layers during microbe invasion, ultimately triggering changes of root cell fates. The progression of legume root interactions with rhizobial bacteria has been addressed in numerous studies. However, tools to globally resolve the succession of molecular events in the host root at the cell type level have been lacking. To this end, we aimed to identify promoters exhibiting cell type enriched expression in roots of the model legume Lotus japonicus, as no comprehensive set of such promoters usable in legume roots is available to date. RESULTS: Here, we use promoter:GUS fusions to characterize promoters stemming from Arabidopsis, tomato (Lycopersicon esculentum) or L. japonicus with respect to their expression in major cell types of the L. japonicus root differentiation zone, which shows molecular and morphological responses to symbiotic bacteria and fungi. Out of 24 tested promoters, 11 showed cell type enriched activity in L. japonicus roots. Covered cell types or cell type combinations are epidermis (1), epidermis and cortex (2), cortex (1), endodermis and pericycle (2), pericycle and phloem (4), or xylem (1). Activity of these promoters in the respective cell types was stable during early stages of infection of transgenic roots with the rhizobial symbiont of L. japonicus, Mesorhizobium loti. For a subset of five promoters, expression stability was further demonstrated in whole plant transgenics as well as in active nodules. CONCLUSIONS: 11 promoters from Arabidopsis (10) or tomato (1) with enriched activity in major L. japonicus root and nodule cell types have been identified. Root expression patterns are independent of infection with rhizobial bacteria, providing a stable read-out in the root section responsive to symbiotic bacteria. Promoters are available as cloning vectors. We expect these tools to help provide a new dimension to our understanding of signaling circuits and transcript dynamics in symbiotic interactions of legumes with microbial symbionts. PMID- 26807141 TI - Gesture for Linguists: A Handy Primer. AB - Humans communicate using language, but they also communicate using gesture - spontaneous movements of the hands and body that universally accompany speech. Gestures can be distinguished from other movements, segmented, and assigned meaning based on their forms and functions. Moreover, gestures systematically integrate with language at all levels of linguistic structure, as evidenced in both production and perception. Viewed typologically, gesture is universal, but nevertheless exhibits constrained variation across language communities (as does language itself ). Finally, gesture has rich cognitive dimensions in addition to its communicative dimensions. In overviewing these and other topics, we show that the study of language is incomplete without the study of its communicative partner, gesture. PMID- 26807142 TI - Current Outcomes of Laparoscopic Duodenal Switch. AB - BACKGROUND: Biliopancreatic diversion with duodenal switch (BPD-DS) has long been considered as the bariatric procedure with the highest peri-operative and long term complication rate. However, modern peri-operative care, including laparoscopic and staged-approach, has significantly reduced the complication rate related to this procedure. The goal of this article is to provide an overview of the current outcomes of laparoscopic BPD-DS in a high volume centre. METHODS: All patients who had a laparoscopic BPD-DS with a hand-sewn anastomosis performed between 2011 and 2015 (N = 566) were reviewed. Data were obtained from our prospectively maintained electronic database and are reported as a Mean +/- standard deviation. RESULTS: The mean age of the 566 patients was 41 +/- 10 years, with 78 % women. Initial body mass index was 49 +/- 6 kg/m(2). There was no 90-days mortality. Hospital stay was 4.5 +/- 3 days. Major 30-days complications occurred in 3.0 % (n = 17) of the patients and minor complications in 2.5 % (N = 14). Excess weight loss was 81 +/- 14 % at 12 m, 88 +/- 13 % at 24 m, 83 +/- 14 % at 36 months. Total body weight loss (kg) was 57 +/- 13 kg at 12 months, 63 +/- 14 kg at 24 months and 61 +/- 17 kg at 36 months. Hemoglobin A1C (HbA1C) dropped from 6.1 +/- 1 % to 4.7 +/- 0.5 % (p < 0.005) and the percentage of patients with an HbA1C above 6 % decreased from 38 to 1.4 % (p < 0.005). Over 21 +/- 12 months follow-up, readmission was required in 3.5 % and reoperation in 0.5 % of the patients. CONCLUSION: The current short and medium-term complication rate of laparoscopic BPD-DS are similar to other mixed bariatric procedures with excellent metabolic outcomes. PMID- 26807144 TI - Disposable screen printed sensor for the electrochemical detection of delta-9 tetrahydrocannabinol in undiluted saliva. AB - BACKGROUND: Cannabis has an adverse effect on the ability to drive safely, therefore a rapid disposable test for Delta(9)-tetrahydrocannabinol (Delta(9) THC), the psychoactive component of cannabis, is highly desirable for roadside testing. RESULTS: A screen printed carbon electrode is used for the N-(4-amino-3 methoxyphenyl)-methanesulfonamide mediated detection of Delta(9)-THC in saliva. Mediator placed in an overlayer was galvanostatically oxidized and reacted with Delta(9)-THC to give an electrochemically active adduct which could be detected by chronoamperometric reduction. Detection of 25-50 ng/mL Delta(9)-THC spiked into undiluted saliva was achieved with a response time of 30 s. A trial of the sensors with four cannabis smokers showed sensitivity of 28 %, specificity of 99 % and accuracy of 52 %. CONCLUSIONS: Rapid electrochemical detection of Delta(9) THC in undiluted saliva has been demonstrated using a disposable sensor, however the sensitivity is lower than acceptable. Further optimization of the assay and sensor format is required to improve the sensitivity of response to Delta(9)-THC. PMID- 26807143 TI - A systematic review of school-based interventions targeting physical activity and sedentary behaviour among older adolescents. AB - Lack of physical activity (PA) and high levels of sedentary behaviour (SB) have been associated with health problems. This systematic review evaluates the effectiveness of school-based interventions to increase PA and decrease SB among 15-19-year-old adolescents, and examines whether intervention characteristics (intervention length, delivery mode and intervention provider) and intervention content (i.e. behaviour change techniques, BCTs) are related to intervention effectiveness. A systematic search of randomised or cluster randomised controlled trials with outcome measures of PA and/or SB rendered 10 results. Risk of bias was assessed using the Cochrane risk of bias tool. Intervention content was coded using Behaviour Change Technique Taxonomy v1. Seven out of 10 studies reported significant increases in PA. Effects were generally small and short-term (Cohen's d ranged from 0.132 to 0.659). Two out of four studies that measured SB reported significant reductions in SB. Interventions that increased PA included a higher number of BCTs, specific BCTs (e.g., goal setting, action planning and self monitoring), and were delivered by research staff. Intervention length and mode of delivery were unrelated to effectiveness. More studies are needed that evaluate long-term intervention effectiveness and target SBs among older adolescents. PMID- 26807145 TI - A Ten year review of alcohol use and major trauma in a Canadian province: still a major problem. AB - BACKGROUND: Alcohol plays a significant role in major traumatic injuries. While the role of alcohol in motor vehicle trauma (MVT) is well described, its role and approaches to prevention in other injury mechanisms is less defined. METHODS: A 10 year retrospective examination of Alberta Trauma Registry (ATR) data was conducted on all major trauma patients (age >= 9 and ISS >= 12) from 2001-2010. The role and prevalence of alcohol is examined. RESULTS: Of 22,457 patients included in our study, only 60 %(n = 13,552) were screened for alcohol use. Of those screened, 38 %(n = 5,170) tested positive for alcohol with a mean blood alcohol concentration (BAC) of 39.4 +/- 21.1 mmol/L. Of the positive screening tests, 82.3 % had BAC levels greater than the common legal driving limit of 17.4 mmol/L (0.08 %). Testing positive was associated with male gender (p < 0.001) and younger age (p < 0.001). The rate of positive alcohol use in major trauma increased from 20.3 % in 2001 to 24.3 % in 2010, corresponding with a screening rate increase from 51.3 % to 61.2 % over the same period. Railway incidents have the highest rate of alcohol involvement (65 %), followed by undetermined-if accidental/self-inflicted (53.5 %) and assault (49 %); motor vehicle traffic (MVT) incidents had a frequency of 25.4 %. CONCLUSIONS: The prevalence of alcohol use in major trauma appears to be increasing in Alberta but the true extent is still underappreciated. Furthermore, the role of alcohol in non-MVT injuries is significant and deserves further attention. The vast majority of patients involved in alcohol-related trauma are legally intoxicated. Alcohol use continues to be a substantial contributor to major trauma in Alberta, and represents an important opportunity to reduce preventable injuries. PMID- 26807146 TI - Attitudes and beliefs about mental illness among church-based lay health workers: experience from a prevention of mother-to-child HIV transmission trial in Nigeria. AB - Common mental disorders are prevalent in Nigeria. Due to stigma and a limited number of trained specialists, only 10% of adults with mental illness in Nigeria receive any care. The Healthy Beginning Initiative is a community-based maternal/child health program that includes screening for perinatal depression and was implemented by lay, volunteer, church-based health advisors (CHAs). The aim of the study was to assess the beliefs and attitudes about mental illness among the CHAs. The study used a cross-sectional survey of 57 CHAs, who completed a 43-item, self-administered questionnaire that assessed their beliefs and attitudes about mental illness. The response rate was 71%. Respondents were mostly female (79%), married (83%) and aged 40-49 years (M = 41.16 SD = 10.48). Most endorsed possession by evil spirits (84%), traumatic events (81%) and witchcraft (60%) as causes of mental illness. A majority (69%) believed that people with mental illness were a nuisance, and less than half (46%) believed that mental disorders were illnesses like any other illness. It is concluded that stigmatizing attitudes and beliefs about mental illness are common among the CHAs. Training for lay health workers in Nigeria should include education on the known bio-psycho-social basis of mental disorders and the role of social inclusion in recovery. PMID- 26807147 TI - A mental health needs assessment of children and adolescents in post-conflict Liberia: results from a quantitative key-informant survey. AB - Between 1989 and 2004, Liberia experienced a devastating civil war that resulted in widespread trauma with almost no mental health infrastructure to help citizens cope. In 2009, the Liberian Ministry of Health and Social Welfare collaborated with researchers from Massachusetts General Hospital to conduct a rapid needs assessment survey in Liberia with local key informants (n = 171) to examine the impact of war and post-war events on emotional and behavioral problems of, functional limitations of, and appropriate treatment settings for Liberian youth aged 5-22. War exposure and post-conflict sexual violence, poverty, infectious disease and parental death negatively impacted youth mental health. Key informants perceived that youth displayed internalizing and externalizing symptoms and mental health-related functional impairment at home, school, work and in relationships. Medical clinics were identified as the most appropriate setting for mental health services. Youth in Liberia continue to endure the harsh social, economic and material conditions of everyday life in a protracted post conflict state, and have significant mental health needs. Their observed functional impairment due to mental health issues further limited their access to protective factors such as education, employment and positive social relationships. Results from this study informed Liberia's first post-conflict mental health policy. PMID- 26807148 TI - Environmental assessment of mild bisulfite pretreatment of forest residues into fermentable sugars for biofuel production. AB - BACKGROUND: Sugar production via pretreatment and enzymatic hydrolysis of cellulosic feedstock, in this case softwood harvest residues, is a critical step in the biochemical conversion pathway towards drop-in biofuels. Mild bisulfite (MBS) pretreatment is an emerging option for the breakdown and subsequent processing of biomass towards fermentable sugars. An environmental assessment of this process is critical to discern its future sustainability in the ever changing biofuels landscape. RESULTS: The subsequent cradle-to-gate assessment of a proposed sugar production facility analyzes sugar made from woody biomass using MBS pretreatment across all seven impact categories (functional unit 1 kg dry mass sugar), with a specific focus on potential global warming and eutrophication impacts. The study found that the eutrophication impact (0.000201 kg N equivalent) is less than the impacts from conventional beet and cane sugars, while the global warming impact (0.353 kg CO2 equivalent) falls within the range of conventional processes. CONCLUSIONS: This work discusses some of the environmental impacts of designing and operating a sugar production facility that uses MBS as a method of treating cellulosic forest residuals. The impacts of each unit process in the proposed facility are highlighted. A comparison to other sugar-making process is detailed and will inform the growing biofuels literature. PMID- 26807149 TI - Predicting compositions of microbial communities from stoichiometric models with applications for the biogas process. AB - BACKGROUND: Microbial communities are ubiquitous in nature and play a major role in ecology, medicine, and various industrial processes. In this study, we used stoichiometric metabolic modeling to investigate a community of three species, Desulfovibrio vulgaris, Methanococcus maripaludis, and Methanosarcina barkeri, which are involved in acetogenesis and methanogenesis in anaerobic digestion for biogas production. RESULTS: We first constructed and validated stoichiometric models of the core metabolism of the three species which were then assembled to community models. The community was simulated by applying the previously described concept of balanced growth demanding that all organisms of the community grow with equal specific growth rate. For predicting community compositions, we propose a novel hierarchical optimization approach: first, similar to other studies, a maximization of the specific community growth rate is performed which, however, often leads to a wide range of optimal community compositions. In a secondary optimization, we therefore also demand that all organisms must grow with maximum biomass yield (optimal substrate usage) reducing the range of predicted optimal community compositions. Simulating two-species as well as three-species communities of the three representative organisms, we gained several important insights. First, using our new optimization approach we obtained predictions on optimal community compositions for different substrates which agree well with measured data. Second, we found that the ATP maintenance coefficient influences significantly the predicted community composition, especially for small growth rates. Third, we observed that maximum methane production rates are reached under high-specific community growth rates and if at least one of the organisms converts its substrate(s) with suboptimal biomass yield. On the other hand, the maximum methane yield is obtained at low community growth rates and, again, when one of the organisms converts its substrates suboptimally and thus wastes energy. Finally, simulations in the three-species community clarify exchangeability and essentiality of the methanogens in case of alternative substrate usage and competition scenarios. CONCLUSIONS: In summary, our study presents new methods for stoichiometric modeling of microbial communities in general and provides valuable insights in interdependencies of bacterial species involved in the biogas process. PMID- 26807151 TI - Prediction of donor splice sites using random forest with a new sequence encoding approach. AB - BACKGROUND: Detection of splice sites plays a key role for predicting the gene structure and thus development of efficient analytical methods for splice site prediction is vital. This paper presents a novel sequence encoding approach based on the adjacent di-nucleotide dependencies in which the donor splice site motifs are encoded into numeric vectors. The encoded vectors are then used as input in Random Forest (RF), Support Vector Machines (SVM) and Artificial Neural Network (ANN), Bagging, Boosting, Logistic regression, kNN and Naive Bayes classifiers for prediction of donor splice sites. RESULTS: The performance of the proposed approach is evaluated on the donor splice site sequence data of Homo sapiens, collected from Homo Sapiens Splice Sites Dataset (HS3D). The results showed that RF outperformed all the considered classifiers. Besides, RF achieved higher prediction accuracy than the existing methods viz., MEM, MDD, WMM, MM1, NNSplice and SpliceView, while compared using an independent test dataset. CONCLUSION: Based on the proposed approach, we have developed an online prediction server (MaLDoSS) to help the biological community in predicting the donor splice sites. The server is made freely available at http://cabgrid.res.in:8080/maldoss. Due to computational feasibility and high prediction accuracy, the proposed approach is believed to help in predicting the eukaryotic gene structure. PMID- 26807150 TI - Cytogenetically visible copy number variations (CG-CNVs) in banding and molecular cytogenetics of human; about heteromorphisms and euchromatic variants. AB - BACKGROUND: Copy number variations (CNVs) having no (obvious) clinical effects were rediscovered as major part of human genome in 2004. However, for every cytogeneticist microscopically visible harmless CNVs (CG-CNVs) are well known since decades. Harmless CG-CNVs can be present as heterochromatic or even as euchromatic variants in clinically healthy persons. RESULTS: Here I provide a review on what is known today on the still too little studied harmless human CG CNVs, point out which can be mixed up with clinically relevant pathological CG CNVs and shortly discuss that the artificial separation of euchromatic submicroscopic CNVs (MG-CNVs) and euchromatic CG-CNVs is no longer timely. CONCLUSION: Overall, neither so-called harmless heterochromatic nor so-called harmless euchromatic CG-CNVs are considered enough in evaluation of routine cytogenetic analysis and reporting. This holds especially true when bearing in mind the so-called two-hit model suggesting that combination of per se harmless CNVs may lead to clinical aberrations if they are present together in one patient. PMID- 26807152 TI - A network of activists for community-oriented integrated care. PMID- 26807153 TI - Holistic General Practice: A Student's Perspective. AB - This patient was a lady in her 50s who had previously been diagnosed with anxiety, depression and rectal cancer. She had undergone neo-adjuvant chemotherapy designed to shrink the tumour before it was removed surgically. However, the cancer responded better than expected to the chemotherapy, and the oncologists could no longer find evidence of active cancer within the patient. The oncologist had recently been speaking with the patient about whether or not she should continue with the surgery they had originally planned. The oncologist was keen to go ahead with the surgery, as it offered the best chance of long term disease free survival. The patient, however, was extremely nervous about going through major surgery, and was less sure that it was the right option now that she had been told that there was no evidence of active cancer. However, she had been unable to come to a definitive decision despite 3 consultations with her oncologist and the surgeons ready to perform the operation and the oncologist had written to the patients GP to this effect. This patient taught me a variety of things. Firstly, the background given to me about this patients' first consultation opened my eyes to the importance of certain parts of the medical history. For example, the rectal cancer was only picked up due to additional symptoms found during the review of systems. The patient consultation that I witnessed was regarding a decision the patient was struggling to make over whether or not to have surgery following seemingly successful neo-adjuvant chemotherapy. The patient was struggling to make this decision due to a lack of support and the GP had scheduled this appointment to help her come to terms with the decision that she needed to make. PMID- 26807154 TI - Promoting healthy behaviours - do we need to practice what we preach? AB - The UK faces a public health challenge arising from unhealthy behaviours. Some health care workers engage in the same unhealthy behaviours as the general population. This paper explores the issues arising from some primary care staff adopting unhealthy behaviours upon healthcare organisations, professional practice and patient perceptions in terms of the promotion of health in the primary care setting. PMID- 26807155 TI - Wally Neuzil : a special woman and a therapist. PMID- 26807156 TI - vSDC: a method to improve early recognition in virtual screening when limited experimental resources are available. AB - BACKGROUND: In drug design, one may be confronted to the problem of finding hits for targets for which no small inhibiting molecules are known and only low throughput experiments are available (like ITC or NMR studies), two common difficulties encountered in a typical academic setting. Using a virtual screening strategy like docking can alleviate some of the problems and save a considerable amount of time by selecting only top-ranking molecules, but only if the method is very efficient, i.e. when a good proportion of actives are found in the 1-10 % best ranked molecules. RESULTS: The use of several programs (in our study, Gold, Surflex, FlexX and Glide were considered) shows a divergence of the results, which presents a difficulty in guiding the experiments. To overcome this divergence and increase the yield of the virtual screening, we created the standard deviation consensus (SDC) and variable SDC (vSDC) methods, consisting of the intersection of molecule sets from several virtual screening programs, based on the standard deviations of their ranking distributions. CONCLUSIONS: SDC allowed us to find hits for two new protein targets by testing only 9 and 11 small molecules from a chemical library of circa 15,000 compounds. Furthermore, vSDC, when applied to the 102 proteins of the DUD-E benchmarking database, succeeded in finding more hits than any of the four isolated programs for 13-60 % of the targets. In addition, when only 10 molecules of each of the 102 chemical libraries were considered, vSDC performed better in the number of hits found, with an improvement of 6-24 % over the 10 best-ranked molecules given by the individual docking programs.Graphical abstractIn drug design, for a given target and a given chemical library, the results obtained with different virtual screening programs are divergent. So how to rationally guide the experimental tests, especially when only a few number of experiments can be made? The variable Standard Deviation Consensus (vSDC) method was developed to answer this issue. Left panel the vSDC principle consists of intersecting molecule sets, chosen on the basis of the standard deviations of their ranking distributions, obtained from various virtual screening programs. In this study Glide, Gold, FlexX and Surflex were used and tested on the 102 targets of the DUD-E database. Right panel Comparison of the average percentage of hits found with vSDC and each of the four programs, when only 10 molecules from each of the 102 chemical libraries of the DUD-E database were considered. On average, vSDC was capable of finding 38 % of the findable hits, against 34 % for Glide, 32 % for Gold, 16 % for FlexX and 14 % for Surflex, showing that with vSDC, it was possible to overcome the unpredictability of the virtual screening results and to improve them. PMID- 26807157 TI - The development of models to predict melting and pyrolysis point data associated with several hundred thousand compounds mined from PATENTS. AB - BACKGROUND: Melting point (MP) is an important property in regards to the solubility of chemical compounds. Its prediction from chemical structure remains a highly challenging task for quantitative structure-activity relationship studies. Success in this area of research critically depends on the availability of high quality MP data as well as accurate chemical structure representations in order to develop models. Currently, available datasets for MP predictions have been limited to around 50k molecules while lots more data are routinely generated following the synthesis of novel materials. Significant amounts of MP data are freely available within the patent literature and, if it were available in the appropriate form, could potentially be used to develop predictive models. RESULTS: We have developed a pipeline for the automated extraction and annotation of chemical data from published PATENTS. Almost 300,000 data points have been collected and used to develop models to predict melting and pyrolysis (decomposition) points using tools available on the OCHEM modeling platform (http://ochem.eu). A number of technical challenges were simultaneously solved to develop models based on these data. These included the handing of sparse data matrices with >200,000,000,000 entries and parallel calculations using 32 * 6 cores per task using 13 descriptor sets totaling more than 700,000 descriptors. We showed that models developed using data collected from PATENTS had similar or better prediction accuracy compared to the highly curated data used in previous publications. The separation of data for chemicals that decomposed rather than melting, from compounds that did undergo a normal melting transition, was performed and models for both pyrolysis and MPs were developed. The accuracy of the consensus MP models for molecules from the drug-like region of chemical space was similar to their estimated experimental accuracy, 32 degrees C. Last but not least, important structural features related to the pyrolysis of chemicals were identified, and a model to predict whether a compound will decompose instead of melting was developed. CONCLUSIONS: We have shown that automated tools for the analysis of chemical information have reached a mature stage allowing for the extraction and collection of high quality data to enable the development of structure-activity relationship models. The developed models and data are publicly available at http://ochem.eu/article/99826. PMID- 26807158 TI - The chronic care model for type 2 diabetes: a systematic review. AB - The chronic care model (CCM) uses a systematic approach to restructure health care systems. The aim of this systematic review was to examine studies that evaluated different elements of the CCM in patients with type 2 diabetes mellitus (T2DM) and to assess the influence of the CCM on different clinical outcomes. There view was performed in the Medline and Cochrane Library electronic databases. The search was limited to randomized controlled trials conducted with T2DM patients. Studies were eligible for inclusion if they compared usual care with interventions that use done or more elements of the CCM and assessed the impact on clinical outcomes. After applying the eligibility criteria, 12 studies were included for data extraction. Of these, six showed evidence of effectiveness of the CCM for T2DM management in primary care as well as significant improvements in clinical outcomes. In the other six studies, no improvements regarding clinical outcomes were observed when comparing the intervention and control groups. Some limitations, such as a short follow-up period and a low number of patients, were observed. Some studies showed that the reorganization of health systems can improveT2DM care. However, it is possible that greater benefits could be obtained through combing all 6 elements of CCM. PMID- 26807159 TI - Jucara pulp supplementation improves glucose tolerance in mice. AB - BACKGROUND: The consumption of hyperlipidic and hypercaloric diet is considered a major factor to promote obesity and the consumption of food with antioxidant properties, like Jucara (Euterpe edulis Mart), could be a tool to prevent the deleterious effect of high white adipose deposition. The aim of the present study was to evaluate the effect of administration of jucara pulp in mice fed a high fat, high-calorie diet on glucose tolerance and adipose tissue inflammatory status. METHODS: Mice were distributed into the following groups: control diet; control diet plus 0.5 % of jucara; control diet plus 2 % of jucara; hypercaloric and hyperlipidic diet; hypercaloric and hyperlipidic diet plus 0.5 % of jucara and hypercaloric and hyperlipidic diet plus 2 % of jucara. Treatments started when mice were 8 weeks old and carried on for a total period of 10 weeks. The serum glucose, triacylglycerol, total cholesterol, insulin, adiponectin, lipopolysaccharides and free fatty acids concentrations were measured. Oral glucose tolerance test was performed. TNF-alpha, IL-6, and IL-10 protein level were determined by ELISA on mesenteric and epididymal white adipose tissues. Determination of catalase activity was realized in the same tissues. Data were analysed using one-way analysis of variance and post hoc analysis was performed with the Tukey's test. RESULTS: The addition of 0.5 % jucara improved glycemic response in animals that consumed normocaloric as well as hypercaloric and hyperlipidic diets (HC). Supplementation with 0.5 and 2 % did not change the body composition of animals that received the HC diet; however, the animals fed the normocaloric diet with 2 % jucara gained body mass. An intake of 2 % jucara in the HC diet promoted a reduction of catalase activity and IL-10 level in epididymal adipose tissue. CONCLUSIONS: These results suggest that with the administration of 0.5 % jucara, the beneficial effects of polyphenols overcome the deleterious effects of macronutrient composition of jucara, whereas with the administration of 2 % jucara promotes damage by the composition of the fruit and overshadows the beneficial effects of polyphenols on glucose metabolism. On the other hand, higher jucara supplementation improves the inflammatory status targeted by the HC diet. PMID- 26807160 TI - Maternal B vitamins: effects on offspring weight and DNA methylation at genomically imprinted domains. AB - BACKGROUND: Inadequate maternal nutrition during early fetal development can create permanent alterations in the offspring, leading to poor health outcomes. While nutrients involved in one-carbon cycle metabolism are important to fetal growth, associations with specific nutrients remain inconsistent. This study estimates associations between maternal vitamins B12, B6 (pyridoxal phosphate [PLP] and 4-pyridoxic acid [PA]), and homocysteine (Hcy) concentrations, offspring weight (birth weight and 3-year weight gain), and DNA methylation at four differentially methylated regions (DMRs) known to be involved in fetal growth and development (H19, MEG3, SGCE/PEG10, and PLAGL1). METHODS: Study participants (n = 496) with biomarker and birth weight data were enrolled as part of the Newborn Epigenetics STudy. Weight gain data were available for 273 offspring. Among 484 mother-infant pairs, DNA methylation at regulatory sequences of genomically imprinted genes was measured in umbilical cord blood DNA using bisulfite pyrosequencing. We used generalized linear models to estimate associations. RESULTS: Multivariate adjusted regression models revealed an inverse association between maternal Hcy concentration and male birth weight (beta = -210.40, standard error (SE) = 102.08, p = 0.04). The offspring of the mothers in the highest quartile of B12 experienced lower weight gain between birth and 3 years compared to the offspring of the mothers in the lowest (beta = 2203.03, SE = 722.49, p = 0.003). Conversely, maternal PLP was associated with higher weight gain in males; higher maternal PLP concentrations were also associated with offspring DNA methylation levels at the MEG3 DMR (p < 0.01). CONCLUSIONS: While maternal concentrations of B12, B6, and Hcy do not associate with birth weight overall, they may play an important role in 3-year weight gain. This is the first study to report an association between maternal PLP and methylation at the MEG3 DMR which may be an important epigenetic tag for maternal B vitamin adequacy. PMID- 26807161 TI - Prognostic factors in Polish patients with BRCA1-dependent ovarian cancer. AB - BACKGROUND: Treatment outcomes appear to be better for ovarian cancer (OC) patients carrying the BRCA1/2 germline mutation than for patients with sporadic OC. However, most published data are for North American, British and Jewish populations. There have been very few studies on treatment outcomes in Central and Eastern European patients with OC. The aim of this study was to analyse prognostic factors in Polish patients with BRCA1-dependent OC (BRCA1-OC). METHODS: The records of patients with OC treated with surgery and chemotherapy at the Centre of Oncology in Krakow, Poland, between 2004 and 2009 were reviewed. Based on family history, a group of 249 consecutive patients fulfilling the criteria for risk of hereditary OC were selected and tested for the germline BRCA1 mutation. Response to combination therapy (surgery and chemotherapy) in the BRCA1-OC group was assessed based on clinical examination, imaging and serum CA125. RESULTS: Germline BRCA1 mutations were detected in 69 of the 249 patients, but three of these patients failed to complete the study. Finally, 66 patients with BRCA1-OC were included in the study group. The median age of the study patients was 49.5 years. All had undergone primary or interval cytoreductive surgery and chemotherapy. Progression occurred in 48 (72.7 %) of the 66 patients and median time to progression was 20 months. The 5-year overall survival rate in was 43.9 % and median survival time was 32.3 months. On multivariate analysis, the endometrial subtype of OC and serum CA125 < 12.5 U/ml at the end of treatment were independent, positive prognostic factors for 5-year overall survival. CONCLUSION: Prognostic factors for favourable treatment outcomes in Polish patients with BRCA1-OC do not appear to differ from those in patients with sporadic OC. The incidence of the endometrial subtype of OC was relatively high (34.9 %) among women in the study. This was unexpected and has not been reported previously. This subtype of OC was an independent prognostic factor for favourable treatment outcomes. PMID- 26807162 TI - A Kalman Filtering Perspective for Multiatlas Segmentation. AB - In multiatlas segmentation, one typically registers several atlases to the novel image, and their respective segmented label images are transformed and fused to form the final segmentation. In this work, we provide a new dynamical system perspective for multiatlas segmentation, inspired by the following fact: The transformation that aligns the current atlas to the novel image can be not only computed by direct registration but also inferred from the transformation that aligns the previous atlas to the image together with the transformation between the two atlases. This process is similar to the global positioning system on a vehicle, which gets position by inquiring from the satellite and by employing the previous location and velocity-neither answer in isolation being perfect. To solve this problem, a dynamical system scheme is crucial to combine the two pieces of information; for example, a Kalman filtering scheme is used. Accordingly, in this work, a Kalman multiatlas segmentation is proposed to stabilize the global/affine registration step. The contributions of this work are twofold. First, it provides a new dynamical systematic perspective for standard independent multiatlas registrations, and it is solved by Kalman filtering. Second, with very little extra computation, it can be combined with most existing multiatlas segmentation schemes for better registration/segmentation accuracy. PMID- 26807163 TI - Epigenetic regulation in chondrocyte phenotype maintenance for cell-based cartilage repair. AB - Loss of hyaline chondrocyte phenotype during the monolayer culture in vitro is a major obstacle for cell-based articular cartilage repair. Increasing evidence implicates an important role of the epigenetic regulation in maintaining the chondrocyte phenotype. DNA methylation, histone modifications and microRNAs have all been shown to contribute to chondrocyte dedifferentiation and hypertrophy. Moreover, the interplay among epigenetic regulators forms a complicated epigenetic network in regulating chondrocyte dedifferentiation. This review provides a detailed overview of the epigenetic regulation in maintaining the chondrocyte phenotype for chondrocyte-based cartilage repair. PMID- 26807164 TI - Epithelial-mesenchymal transition in gastric cancer. AB - Gastric cancer (GC) is one of the most common malignancies worldwide with poor prognosis for lack of early detection and effective treatment modalities. The significant influence of tumor microenvironment on malignant cells has been extensively investigated in this targeted-therapy era. Epithelial-mesenchymal transition (EMT) is a highly conserved and fundamental process that is critical for embryogenesis and some other pathophysiological processes, especially tumor genesis and progression. Aberrant gastric EMT activation could endow gastric epithelial cells with increased mesenchymal characteristics and less epithelial features, and promote cancer cell stemness, initiation, invasion, metastasis, and chemo-resistance with cellular adhesion molecules especially E-cadherin concomitantly repressed, which allows tumor cells to disseminate and spread throughout the body. Some pathogens, stress, and hypoxia could induce and aggravate GC via EMT, which is significantly correlated with prognosis. GC EMT is modulated by diverse micro-environmental, membrane, and intracellular cues, and could be triggered by various overexpressed transcription factors, which are downstream of several vital cross-talking signaling pathways including TGF-beta, Wnt/beta-catenin, Notch, etc. microRNAs also contribute significantly to GC EMT modulation. There are currently some agents which could suppress GC EMT, shedding light on novel anti-malignancy strategies. Investigating potential mechanisms modulating GC cell EMT and discovering novel EMT regulators will further elucidate GC biology, and may provide new biomarkers for early GC detection and potentially efficient targets for preventative and curative anti-GC intervention approaches to prevent local and distant invasions. PMID- 26807166 TI - Effects of human umbilical cord mesenchymal stem cell transplantation combined with minimally invasive hematoma aspiration on intracerebral hemorrhage in rats. AB - This study is to investigate the effects of human umbilical cord-mesenchymal stem cells (HUC-MSCs) transplantation combined with minimally invasive hematoma aspiration on neural functional recovery and p53 gene expression in rats with intracerebral hemorrhage (ICH). Collagenase type-IV was injected to the caudate nucleus of the rats to make ICH models. One hundred and twenty Sprague-Dawley rats with successful modeling were randomly divided into 4 groups, including the ICH group, hematoma aspiration group, HUC-MSCs transplantation group and HUC-MSCs transplantation combined with hematoma aspiration group (combination group). Neural functional status of the rats was assessed by modified neurological severity score (mNSS). Expression of p53 in the cerebral tissues surrounding ICH was detected by immunohistochemical assays. The scores of mNSS and the expression of p53 gene in the hematoma aspiration group, the HUC-MSCs transplantation group and the combination group were significantly lower than those in the ICH group at each indicated time point (p < 0.05). Intriguingly, mNSS scores and p53 expression in the combination group were significantly lower than those in the hematoma aspiration group on day 7, 14 and 30 (p < 0.05), and significantly lower than those in the HUC-MSCs transplantation group on day 14 and 30 (p < 0.05). HUC MSCs transplantation combined with minimally invasive hematoma aspiration is more effective than either therapy alone in rats with ICH and could distinctly reduce the damage of nerve cells. PMID- 26807165 TI - Histone methyltransferases: novel targets for tumor and developmental defects. AB - Histone lysine methylation plays a critical role in epigenetic regulation of eukaryotes. To date, studies have shown that lysine residues of K4, K9, K27, K36 and K79 in histone H3 and K20 in histone H4 can be modified by histone methyltransferases (HMTs). Such histone methylation can specifically activate or repress the transcriptional activity to play a key role in gene expression/regulation and biological genetics. Importantly, abnormities of patterns or levels of histone methylation in higher eukaryotes may result in tumorigenesis and developmental defects, suggesting histone methylation will be one of the important targets or markers for treating these diseases. This review will outline the structural characteristics, active sites and specificity of HMTs, correlation between histone methylation and human diseases and lay special emphasis on the progress of the research on H3K36 methylation. PMID- 26807167 TI - Identification of biomechanical force as a novel inducer of epithelial mesenchymal transition features in mechanical stretched skin. AB - Biomechanical cues of the microenvironment are recognized as potent regulators of cell behaviors. Skin regeneration induced by tissue expansion has been confirmed by results of experimental and clinical studies. However, it is still unknown whether skin regeneration induced by mechanical factor is the same biological process as skin morphogenesis during embryonic development. In order to explore the potential role of biomechanical force (BioF) in skin regeneration and whether epithelial-mesenchymal transition (EMT) is induced by BioF, continuous mechanical tension (CMT) at 10% elongation was applied to human keratinocytes in vitro for 12, 24, 48 and 72 hours. Cell proliferation and differentiation were analyzed, including the expression of markers of EMT: vimentin, FSP1, E-cadherin and N cadherin. Normal and mechanical stretched skin specimens collected from mice were examined by immunofluorescence analysis and RT-PCR. We found that BioF promoted the proliferation and inhibited differentiation of keratinocytes in vitro. The expression of markers of EMT vimentin, FSP1, E-cadherin and N-cadherin were transiently up-regulated by BioF. Keratinocytes activation, epidermal thickening and EMT features were also observed in the stretched epidermis of mice, compared to normal mice. Furthermore, the mechanism of BioF induced EMT was found to be the enhanced autocrine effect of TNF-alpha, in part, and direct activation of the NF-kappaB pathway. Collectively, BioF promoted the proliferation of keratinocytes by transiently inducing some EMT features. BioF, as a vital biomechanical cue of the microenvironment of skin, was identified to be a novel inducer of EMT, regulating keratinocytes' proliferation, differentiation and homeostasis of skin tissue. PMID- 26807168 TI - Norcantharidin inhibits renal interstitial fibrosis by downregulating PP2Ac expression. AB - Norcantharidin (NCTD) has been proven to be able to attenuate renal interstitial fibrosis, but the exact molecular mechanism is still unknown. This study investigated the relationship between the anti-fibrotic effect of NCTD and its inhibition on PP2Ac expression. Here, PP2Ac was found to be positively correlated with extracellular matrix accumulation in the rat unilateral ureteral obstruction (UUO) model. Additional experiments showed that the PP2A inhibitor (okadaic acid) can ameliorate renal interstitial fibrosis by inhibiting the expression of fibronectin (FN) and collagen I (Col-I) and reversing tubular epithelial-to mesenchymal transition in vivo and in vitro. In vitro experiments also demonstrated that ectopic over-expression of PP2Ac has a profibrotic effect in HK 2 cells. Moreover, NCTD was able to downregulate PP2Ac expression, decrease FN, Col-I, alpha-SMA expression, and increase E-cadherin expression in a dose dependent manner both in vivo and in vitro. In particular, it was demonstrated that NCTD induced no evident changes in the expression of FN, Col-I, alpha-SMA and E-cadherin in HK-2 cells after PP2Ac was knocked down by shRNA. These results indicated that NCTD exerts an anti-fibrosis effect via inhibition of PP2Ac expression. Thus, PP2Ac could be a promising target for intervention in renal interstitial fibrosis. PMID- 26807169 TI - miR-485-5p acts as a negative regulator in gastric cancer progression by targeting flotillin-1. AB - MicroRNAs (miRNAs) play important roles in cancer progression including gastric cancer. miR-485-5p is reported as a potential suppressor in breast cancer, but its expression, cellular function and clinic features in gastric cancer is not known. In our study, we found that miR-485-5p expression was down-regulated in gastric cancer cell lines. miR-485-5p could inhibit gastric cancer cell growth in vitro and in vivo. We also found that miR-485-5p suppressed gastric cancer cell metastasis and sphere formation. It was confirmed flotillin-1 (Flot1) as a direct target of miR-485-5p, and up-regulation of miR-485-5p could decrease expression of Flot1 in gastric cancer cells. Further investigation showed that ectopic expression of Flot1 partially reversed the inhibition effect of enforced miR-485 5p expression on the malignant phenotypes of gastric cancer cells. The low expression of miR-485-5p in gastric cancer tissues was related to advanced clinical features and poorer prognosis. Our study suggested that miR-485-5p could be a potential prognostic marker and functions as a tumor suppressor in human gastric cancer by post-transcriptionally targeting Flot1. PMID- 26807170 TI - The change tendency of PI3K/Akt pathway after spinal cord injury. AB - Spinal cord injury (SCI) refers to the damage of spinal cord's structure and function due to a variety of causes. At present, many scholars have confirmed that apoptosis is the main method of secondary injury in spinal cord injury. In view of understanding the function of PI3K/Akt pathway on spinal cord injury, this study observed the temporal variation of key molecules (PI3K, Akt, p-Akt) in the PI3K/Akt pathway after spinal cord injury by immunohistochemistry and Western blot. The results showed that the expression of PI3K, Akt and p-Akt display a sharp increase one day after the spinal cord injury, and then it decreased gradually with the time passing by, but the absolute expression was certainly higher than the normal group. These results indicate that the PI3K/Akt signaling pathway is involved in the spinal cord injury and the mechanism may be related to apoptosis. PMID- 26807171 TI - TNF receptor-associated factor 6 (TRAF6) mediates the angiotensin-induced non canonical TGF-beta pathway activation of c-kit(+) cardiac stem cells. AB - Cardiac stem cells (CSCs) can differentiate into cardiac muscle-like cells upon stimulation by angiotensin II (Ang II). TNF receptor-associated factor 6 (TRAF6) has been shown to promote JNK- and p38-induced myogenic differentiation and mediate Smad-independent activation of TGF-beta. However, the detailed mechanisms underlying the activation of these signaling pathways are not entirely known. Herein, we hypothesized that Ang II could promote the differentiation of CSCs into cardiac muscle-like cells by non-canonical TGF-beta/TRAF6 signaling pathway, and sought to test the hypothesis. C-kit(+) CSCs were isolated from neonatal Sprague Dawley (SD) rats, and their c-kit status was confirmed with immunofluorescence staining. A TGF-beta type I receptor inhibitor (SB431542) was used to inhibit SMAD2/3 phosphorylation. The small interfering RNA (siRNA) mediated knockdown of TRAF6 was used to investigate the role of TRAF6 in TGF-beta signaling. Rescue of TRAF6 siRNA transfected cells with a 3'UTR-deleted siRNA insensitive construct was performed to rule out any off-target effects of the siRNA. TRAF6 dominant-negative (TRAF6DN) vector was constructed and used to infect c-kit(+) CSCs. Our results showed that the increase in JNK and p38 activation by Ang-II was blocked by siRNA. After transfection by TRAF6-siRNA or Ad-TRAF6, the cardiac specific markers and Wnt signaling proteins were tested by Western blotting. Physical interactions between TRAF6 and TGF-beta receptors were studied by co-immunoprecipitation. Forced expression of TRAF6 enhanced the expression of cTnT and Cx-43 but inhibited the expression of Wnt3a.Our data suggested that TRAF6 mediated Ang II-induced differential responses in c-kit(+) CSCs via the non-canonical TGF-beta signaling pathway. PMID- 26807172 TI - A novel silk fibroin nanofibrous membrane for guided bone regeneration: a study in rat calvarial defects. AB - A novel membrane for guided bone regeneration (GBR), constituting silk fibroin (SF) nanofiber from native silk nanofibril solution, was prepared by electrospinning process. Another barrier membrane, a collagen-type membrane (Bio Gide(r)), was used as a comparative sample. Twelve healthy male Sprague-Dawley rats were used in this study. Bilateral round defects were created in the calvarial bone. The bone regenerative efficacy was evaluated in rat calvarial defects. Animals were killed at 4 and 12 weeks. Bone regeneration was analyzed using micro-computed tomography and histological analysis. The SF nanofibrous membrane showed superior results with regard to mechanical tensile properties. At 4 weeks, the bone volume and collagen I positive areas in the SF group were greater than in the Bio-Gide group. At 12 weeks, the defect had completely healed with new bone in both the groups. In conclusion, the SF nanofibrous membranes showed satisfactory mechanical stability, good biocompatibility, slow degradability, and improved new bone regeneration without any adverse inflammatory reactions. Considering the low cost and low risk of disease transmission, the SF nanofibrous membrane is a potential candidate for GBR therapy compared with the widely used collagen membranes. PMID- 26807173 TI - Loss of miR-532-5p in vitro promotes cell proliferation and metastasis by influencing CXCL2 expression in HCC. AB - MicroRNAs (miRNAs) have been widely reported, which play important roles in cancer development. CXCL2 acts as an oncogene, however, its regulation by miRNAs is not clear in hepatocellular carcinoma (HCC). In our research, it is aimed to study the role of CXCL2 in HCC and the regulation of its expression by miRNAs. Firstly, we found that CXCL2 was up-regulated in the blood of patients with HCC and cell lines compared with the normal controls. CXCL2 could enhance HCC cell proliferation and metastasis. miR-532-5p was predicted as a regulatory miRNA of CXCL2 in HCC, and negatively associated with CXCL2 in HCC samples. It was also verified that miR-532-5p inhibited cell proliferation and metastasis of HCC cells by inhibition CXCL2. Collectively, our findings suggested that miR-532-5p may function as a tumor suppressor in HCC by targeting CXCL2. PMID- 26807174 TI - Linc-POU3F3 promotes cell proliferation in gastric cancer via increasing T-reg distribution. AB - Long noncoding RNA (lncRNA) have been proved to participate in the oncogenesis or development of gastrointestinal tumors. In this study, we aimed to identify the function of lncRNAs in the differentiation of peripheral blood T cells especially the distribution of regulatory T cells (T-reg) in gastric cancer. The distribution of T-reg was detected by flow cytometry. Peripheral blood T-reg cells were significantly up-regulated in plasma samples of gastric cancer patients. LncRNA microarray detection indicated an aberrant expression profiling of lncRNAs in T-reg cells between gastric cancer patients and controls in which linc-POU3F3 was selected as a potential biomarker with the highest fold change value as well as the most stable expression level in each group. In addition, over-expression of linc-POU3F3 elevated Treg distribution in vitro and promoted tumor cell proliferation in the co-culture system. We further found that linc POU3F3 could recruit TGF-beta which increased the phosphorylation of SMAD2/3. In conclusion, we found that linc-POU3F3 could promote the distribution of Tregs in peripheral blood T cell which caused an enhanced cell proliferation of gastric cancer cells by recruiting TGF-beta as well as activating TGF-beta signal pathway. This finding may provide a theoretical basis for the further exploration of lncRNAs function in immune cell cells of gastric cancer. PMID- 26807175 TI - The anti-apoptosis effect of MLAA-34 in leukemia and the beta-catenin/T cell factor 4 protein pathway. AB - Objective This study aims to observe the effects of MLAA-34 gene in leukemia and explore its mechanism. Methods MLAA-34 RNAi vector was constructed. NOD/SCID mice and 293T cells, K562 cells, HL60 cells and U937 cells were used in this study. They were divided into MLAA-34-siRNA group and control group. The proliferation ability and apoptosis of cells were detected. The expression levels of beta Catenin and TCF 4 were determined using western blotting and immunohistochemical methods. Results There was significant correlation between MLAA-34 gene and U937 cell proliferation, the apoptosis rates of U937 cells with siRNA infection were higher than that of control group. There were significant differences in the expression levels of beta-Catenin and TCF 4 between U937 cells and U937 with MLAA 34-siRNA cells group. Conclusions MLAA-34 gene had anti-apoptotic effect in leukemia, which maybe through the beta-Catenin/TCF 4 pathway. PMID- 26807176 TI - Healing of cancellous fracture in a novel mouse model. AB - Fractures are one of the most prevalent clinical conditions worldwide. Among them, cancellous fracture is a major cause of extremities fractures. Unfortunately, it is largely unknown about how is the healing of cancellous fracture. In the current study, we present a novel cancellous fracture mice model, which successfully mimic clinical cancellous fracture scenario. Next, we showed that the newly repaired trabeculae in fracture healing zone were thicker than normal bone tissue with more sufficient local blood supply. There are more osteoclasts reside in the fracture healing zone than normal bone tissue and these osteoclasts distributed more closely and densely. Moreover, the early repairing bone mass in fracture healing zone was not fully collagen loaded as normal bone tissue. Comparing to similar cell proliferation activity, upregulated local cell function play more important role in the cancellous fracture repair. PMID- 26807177 TI - Dysregulated expression of microRNAs and mRNAs in myocardial infarction. AB - Acute myocardial infarction (AMI) is a major cause of mortality in the general population. However, the molecular phenotypes and therapeutic targets of AMI patients remain unclear. By profiling genome-wide transcripts and microRNAs (miRNAs) in a cohort of 23 AMI patients and 23 non-AMI patients, we found 218 dysregulated genes identified in the infarcted heart tissues from AMI patients relative to non-AMI controls. Pathway enrichment analysis of the dysregulated genes pointed to cell signaling/communication, cell/organism defense and cell structure/motility. We next compared the expression profiles of potential regulating miRNAs, suggesting that dysregulation of a number of AMI-associated genes (e.g., IL12A, KIF1A, HIF1alpha and CDK13) may be attributed to the dysregulation of their respective regulating miRNAs. One potentially pathogenic miRNA-mRNA pair, miR-210-HIF1alpha, was confirmed in a mouse model of myocardial infarction (MI). Inhibition of miR-210 expression improved the survival and cardiac function of MI mice. In conclusion, we presented the pathologic relationships between miRNAs and their gene targets in AMI. Such deregulated microRNAs and mRNAs like miR-210 serve as novel therapeutic targets of AMI. PMID- 26807178 TI - Erythropoietin regulates Treg cells in asthma through TGFbeta receptor signaling. AB - Asthma is a chronic inflammatory disorder of the airways, the development of which is suppressed by regulatory T cells (Treg). Erythropoietin (EPO) is originally defined as a hematopoietic growth factor. Recently, the anti inflammatory effects of EPO in asthma have been acknowledged. However, the underlying mechanisms remain ill-defined. Here, we showed that EPO treatment significantly reduced the severity of an ovalbumin (OVA)-induced asthma in mice, seemingly through promoting Foxp3-mediated activation of Treg cells in OVA treated mouse lung. The activation of Treg cells resulted from increases in transforming growth factor beta1 (TGFbeta1), which were mainly produced by M2 macrophages (M2M). In vitro, Co-culture with M2M increased Foxp3 levels in Treg cells and the Treg cell number, in a TGFbeta receptor signaling dependent manner. Moreover, elimination of macrophages abolished the therapeutic effects of EPO in vivo. Together, our data suggest that EPO may increase M2M, which activate Treg cells through TGFbeta receptor signaling to mitigate the severity of asthma. PMID- 26807179 TI - Regulation of beta-catenin-mediated esophageal cancer growth and invasion by miR 214. AB - The malignancy of esophageal cancer (EC) is largely due to its fast growth and invasion, in which WNT/beta-catenin signaling plays a critical role. Hence, suppression of beta-catenin signal transduction in EC cells may inhibit cancer growth and metastases. Among all microRNAs (miRNAs), miR-214 has been shown as a tumor suppressor in many cancers, but has yet studied in EC. Here we found that EC specimens had significant higher levels of beta-catenin, and significantly lower levels of miR-214, compared to paired non-EC tissue. The levels of beta catenin and miR-214 were inversely correlated in EC specimens. Bioinformatics analyses showed that miR-214 bound to 3'-UTR of beta-catenin mRNA in EC cells to inhibit its translation. Overexpression of miR-214 decreased beta-catenin protein, while depletion of miR-214 increased beta-catenin protein in EC cells, without altering beta-catenin mRNA levels. Overexpression of miR-214 in EC cells inhibited cell growth and invasion, while depletion of miR-214 in EC lines increased cell growth and invasion. Taken together, our data demonstrate a previously unappreciated role for miR-214 in suppression of beta-catenin-mediated EC cell growth and invasion, and highlight miR-214 as a potent suppressor of EC. PMID- 26807180 TI - Factor Xa induces pro-inflammatory cytokine expression in RAW 264.7 macrophages via protease-activated receptor-2 activation. AB - Coagulation proteases have been suggested to trigger a diversity of inflammatory responses in addition to their critical role in the coagulation cascade. It has been well established that the inflammatory and coagulation pathways are invariably linked. However, the mechanisms through which coagulation protease factor Xa (FXa) causes inflammation remain unclear. Thus, we assessed the pro inflammatory effects of FXa in RAW 264.7 macrophages. We show that FXa elicits signal transduction in RAW 264.7 macrophages. FXa-induced signal transduction was dependent on the activation of protease-activated receptor 2 (PAR-2), PAR-2 desensitization but not PAR-1 desensitization abolished FXa-induced ERK1/2 phosphorylation. The PAR-2-dependent cellular effects of FXa led to the expression of pro-inflammatory cytokines IL-6, IL-8, TNF-alpha and IFN-gamma in RAW 264.7 macrophages. Furthermore, a specific inhibitor of the ERK1/2 pathway, U0126, decreased the FXa-induced pro-inflammatory cytokines expression significantly. Taken together, our data indicate that FXa induces PAR-2-dependent pro-inflammatory activity in RAW 264.7 macrophages through the ERK1/2 pathway. PMID- 26807181 TI - Chloroquine attenuates LPS-mediated macrophage activation through miR-669n regulated SENP6 protein translation. AB - Chloroquine (CQ) has been shown to inhibit Toll-like receptor 4 (TLR4)-mediated monocyte and macrophage activation induced by lipopolysaccharide (LPS). However, the underlying mechanisms have not been completely elucidated. Recently, SUMO specific protease 6 (SENP6) has been reported to suppress LPS-induced activation of macrophages through deSUMOlation of NF-kappaB essential modifier (NEMO). Here, we studied whether this molecular pathway may also be involved in CQ/LPS model. We found that CQ dose-dependently increased SENP6 protein, but not mRNA, in mouse macrophages, RAW264.7 cells. Overexpression of SENP6 in RAW264.7 cells significantly decreased the LPS-induced release of pro-inflammatory proteins, TNF alpha, IL-6 and IFN-gamma, while depletion of SENP6 in RAW264.7 cells significantly increased these proteins. Moreover, in LPS-treated RAW264.7 cells, CQ dose-dependently decreased the levels of microRNA-669n (miR-669n), which bound to 3'-UTR of SENP6 mRNA to inhibit its translation. Overexpression of miR-669n decreased SENP6, resulting in increased production of TNF-alpha, IL-6 and IFN gamma in RAW264.7 cells, while depletion of miR-669n increased SENP6, resulting in decreased production of TNF-alpha, IL-6 and IFN-gamma in RAW264.7 cells. In vivo, delivery of miR-669n plasmids augmented the effects of LPS, while delivery of antisense of miR-669n (as-miR-669n) plasmids abolished the effects of LPS. Taken together, our data demonstrate a previously unappreciated molecular control of LPS-induced macrophage activation by CQ, through miR-669n-regulated SENP6 protein translation. PMID- 26807182 TI - MiRNA-125b inhibits proliferation and migration by targeting SphK1 in bladder cancer. AB - BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNAs (18-25 nucleotides) that post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs.The purpose of this study was to investigate the expression levels of miR-125b in human bladder cancer and its potential role in disease pathogenesis. METHODS: The expression level of miR-125b was measured in 40 bladder cancer specimens and adjacent normal breast tissues by quantitative polymerase chain reaction (qPCR). MTT and colony formation assays, transwell, cell cycle assays were conducted to explore the potential function of miR-125b in human T24 bladder cancer cells. Luciferase reporter assays were performed to analyze the regulation of putative target of miR-125b. The effects of modulating miR-125b on endogenous levels of this target were subsequently confirmed via qRT-PCR and Western blot. RESULTS: The expression of miR-125b in bladder cancer specimens was lower than adjacent normal tissues (P < 0.05). Overexpression of miR-125b inhibited cellular growth, suppressed cellular migration and caused an accumulation of cells in the G1 phase of the cell cycle, Luciferase assays revealed that miR-125b directly targeted the 3'UTR of SphK1. Overexpression of miR-125b led to the downregulation of SphK1 and protein level as assessed by qRT-PCR and Western blot. Targeted knockdown of SphK1 by siRNA significantly inhibited the proliferation of T24 bladder cancer cells. CONCLUSIONS: These findings suggest that miR-125b may act as a tumor suppressor gene in bladder cancer and that, in the future, targeting of this miRNA may provide a novel strategy for the diagnosis and treatment of patients with this lethal disease. PMID- 26807183 TI - Role of MK2 signaling pathway in the chronic compression of cervical spinal cord. AB - OBJECTIVE: In this study, chronic compression of cervical spinal cord was introduced into twy/twy mice and the role of MK2 signaling pathway was investigated in this disease. METHODS: twy/twy mice aged 6-24 weeks were used and the inflammatory response in the cervical spinal cord was observed. The Institute of Cancer Research (ICR) mice were used as controls. MK2 inhibitor (PF-3644022, 30 mg/kg) was administered intragastrically to twy/twy mice. The motor behavior was firstly observed in these three groups by Catwalk gait analysis. And the cervical spinal cord between C2 and C3 of vertebral segments was analyzed by MRI and Western blot assay. RESULTS: The stride length of paws and interlimb coordination reduced in twy/twy mice. However, at 4 weeks after PF-3644022 treatment, a marked improvement was observed in the motor function. The expressions of inflammation related factors (such as IL-1beta, NF-kappaB, TNF alpha, MK2 and p-MK2) and apoptosis related proteins (such as cleaved caspase-8 and bax/bcl-2) in the spinal cord of twy/twy mice significantly increased as compared to controls, but 4-week treatment with PF-3644022 markedly reduced the expressions of these factors and apoptotic proteins in the cervical spinal cord. CONCLUSION: MK2 signaling pathway is involved in the chronic compression induced inflammation of the cervical spinal cord. Thus, to inhibit the MK2 pathway may used to improve the outcome and prevent the deterioration of neurological dysfunction. PMID- 26807184 TI - Cross regulation between hypoxia-inducible transcription factor-1alpha (HIF 1alpha) and transforming growth factor (TGF)-beta1 mediates nickel oxide nanoparticles (NiONPs)-induced pulmonary fibrosis. AB - Numerous analyses including in vivo and in vitro experiments have demonstrated that inhalation exposure of NiONPs can result in pulmonary fibrosis. However, the potential mechanisms of this pathological process remain elusive. Here, we investigate the role of HIF-1alpha and TGF-beta1 in NiONPs-induced pulmonary fibrosis with a focus on the interplay of the above two proteins. In vivo, male Sprague&Dawley rats were exposed to NiONPs and pulmonary fibrosis was demonstrated using H&E staining and immunochemistry of alphaSMA. In vitro, NiONPs contributed to cell proliferation and increased expressions of collagen-1 and alphaSMA in human fetal lung fibroblasts. Both HIF-1alpha and TGF-beta1 were upregulated by NiONPs treatment. Inhibition of HIF-1alpha reduced TGF-beta1 expression and downregulation of TGF-beta1 reduced HIF-1alpha protein level. Mechanism investigation revealed that TGF-beta1 affects nuclear translocation activity of HIF-1alpha. Taken together, these finding provide evidence that HIF 1alpha and TGF-beta1 act in synergy to foster NiONPs-induced pulmonary fibrosis, and the cross talk between them is a pivotal mechanism of pulmonary fibrosis. PMID- 26807185 TI - Dspp mutations disrupt mineralization homeostasis during odontoblast differentiation. AB - The main pathological feature in isolated hereditary dentin disorders is the abnormality of dentin mineralization. Dentin sialophosphoprotein (DSPP) gene is the only identified causative gene for the disorders. The present study aims to explore the molecular association between Dspp mutations and the disrupted mineralization homeostasis during odontoblast differentiation. We generated lentivirus constructs with the mouse full-length wild type Dspp cDNA and 3 Dspp mutants and transfected them into mouse odontoblast-lineage cells (OLCs) which were then performed 21-day mineralization inducing differentiation. The formation of mineralized nodules was obviously fewer in mutants. Digital Gene Expression (DGE) showed that Dspp mutation affected the OLC differentiation in a degree. Further examination validated that Dspp (LV-Dspp) overexpressing OLCs possessed the ability to strictly orchestrate framework for mineralization inductors like Bmp2, Col1 and Runx2, and proliferative markers for mineralization like Alp and Ocn, as well as mineral homeostasis feedback regulators Mgp and Htra1. However, the missense mutation in Dspp signal peptide region (LV-M2) and the nonsense mutation (LV-M5) broke this orchestration. The results suggested that the mutant Dspp disrupt the dynamic homeostasis of mineralization during OLC differentiation. We are the first to use full-length mouse Dspp gene expression system to explore the mineralization mechanism by which inductors and inhibitors adjust each other during odontoblast differentiation. Our findings shed new light on association between Dspp and the dynamic homeostasis of mineralization inductors and inhibitors, and indicate the disruption of mineralization homeostasis might be a crucial reason for Dspp mutations resulting in dentin disorders. PMID- 26807186 TI - Effects of siRNA-mediated silencing of myeloid cell leukelia-1 on the biological behaviors and drug resistance of gastric cancer cells. AB - OBJECTIVE: This study was to investigate the effects of siRNA mediated silencing of myeloid cell leukelia-1 (Mcl-1) on the biological behaviors and drug resistance of human drug-resistant gastric cancer (GC) cell lines, and to explore the potential mechanisms. METHODS: siRNA targeting Mcl-1 mRNA were designed and independently transfected into SGC-7901/VCR and SGC-7901/DDP. Cell proliferation and drug sensitivity were examined by MTT assay. Cell apoptosis and cell cycle were detected by flow cytometry. Cell Invasion and migration abilities were detected by transwell chamber assays. The expressions of drug-resistance-related genes and apoptosis-related proteins were detected by quantitative real-time PCR and Western blot assay, respectively. RESULTS: siRNA effectively inhibited the Mcl-1 expression, lowered the proliferation rate (P<0.05), raised the apoptosis rate (P<0.05), and arrested cells in S-phase (P<0.05). After inhibiting Mcl-1, the cell migration and invasion decreased (P<0.05), the resistance to VCR, DDP and 5-Fu was reversed to different extents (P<0.05), TS mRNA expression increased significantly (P<0.05), MDR1 remained unchanged (P>0.05), but DPD and TOP2A decreased significantly (P<0.05). Following Mcl-1 silencing, Bcl-2 was over expressed in VCR-siRNA group, but the expressions of Fas and survivin reduced markedly (P<0.05); Bcl-2 and Fas expressions decreased significantly in DDP-siRNA group (P<0.05), but survivin expression remained unchanged. CONCLUSION: Mcl-1 is implicated in the proliferation, invasion, apoptosis and drug resistance of GC cells, and may be a promising target for the therapy of GC. PMID- 26807187 TI - Increased matrix metalloproteinase-2 expression and reduced tissue factor pathway inhibitor-2 expression correlate with angiogenesis and early postoperative recurrence of pancreatic carcinoma. AB - Matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 are known to influence tumor angiogenesis and progression. This work aimed to describe the levels of MMP-2 and TFPI-2 expression associated with tumor angiogenesis and early postoperative recurrence in patients with pancreatic carcinoma. Expression of MMP-2 and TFPI-2 in carcinoma tissues and paracarcinomatous tissues was assayed by immunostaining. Expression of vascular endothelial growth factor (VEGF) and CD34 in tumor tissues was also assayed by immunostaining. The correlations of MMP-2 and TFPI-2 with VEGF, microvessel density (MVD), and early postoperative recurrence were analyzed. The results showed that MMP-2 expression was significantly increased (P < 0.05) and TFPI-2 expression was significantly decreased (P < 0.001) in carcinoma tissues compared with paracarcinomatous tissues. MMP-2 expression was positively correlated with VEGF (r = 0.594, P < 0.001) and MVD (r = 0.432, P < 0.001) in carcinoma tissues. TFPI-2 expression was negatively correlated with VEGF (r = -0.654, P < 0.001) and MVD (r = -0.360, P < 0.001) in carcinoma tissues. Multivariate logistic regression analysis showed that up-regulated MMP-2 and down-regulated TFPI-2 were independent predictors of early postoperative recurrence of pancreatic carcinoma. Receiver operating characteristic curve analysis showed that the combination of MMP-2 and TFPI-2 was a reliable predictive model of early recurrence. We conclude that increased MMP-2 expression and reduced TFPI-2 expression are closely linked to angiogenesis and early postoperative recurrence of pancreatic carcinoma. Immunohistochemical assay of MMP-2 and TFPI-2 may be useful for predicting early relapse of pancreatic carcinoma after surgery. PMID- 26807188 TI - Low thrombospondin 2 expression is predictive of low tumor regression after neoadjuvant chemoradiotherapy in rectal cancer. AB - BACKGROUND: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is the mainstay of treatment for locally advanced rectal cancer. Several heparin binding associated proteins have been reported to play a critical role in cancer progression. However, the clinical relevancies of such proteins and their associations with CCRT response in rectal cancer have not yet to be fully elucidated. METHODS: The analysis of a public transcriptome of rectal cancer indicated that thrombospondin 2 (THBS2) is a predictive factor for CCRT response. Immunohistochemical analyses were conducted to evaluate the expression of THBS2 in pretreatment biopsy specimens from rectal cancer patients without distant metastasis. Furthermore, the relationships between THBS2 expression and various clinicopathological factors or survival were analyzed. RESULTS: Low expression of THBS2 was significantly associated with advanced pretreatment tumor (P<0.001) and nodal status (P=0.004), post-treatment tumor (P<0.001) and nodal status (P<0.001), increased vascular invasion (P=0.003), increased perineural invasion (P=0.023) and inferior tumor regression grade (P=0.015). In univariate analysis, low THBS2 expression predicted worse outcomes for disease-free survival, local recurrence-free survival and metastasis-free survival (all P<0.001). In multivariate analysis, low expression of THBS2 still served as a negative prognostic factor for disease-free survival (Hazard ratio=3.057, P=0.002) and metastasis-free survival (Hazard ratio=3.362, P=0.012). CONCLUSION: Low THBS2 expression was correlated with advanced disease status and low tumor regression after preoperative CCRT and that it acted as an independent negative prognostic factor in rectal cancer. THBS2 may represent a predictive biomarker for CCRT response in rectal cancer. PMID- 26807189 TI - Long non-coding RNA derived miR-205-5p modulates human endometrial cancer by targeting PTEN. AB - OBJECTIVE: This study was to investigate the roles of lncRNA associated competitive endogenous RNAs (ceRNAs) network in the endometrial cancer (EC). METHODS: StarbaseV2.0 online software was used to predict the most probable lncRNAs which contain miR-205-5p binding site and are competent to interact with miR-205-5p. Then, lncRNAs which had decreased expression in EC compared with normal endometrium and conformed to the polyadenylated characteristics of lncRNAs were selected and then lncRNAs associated with miR-205-5p-PTEN network were identified. RESULTS: Two novel genes RP11-395G23.3 and LA16c-313D11.11 associated with endometrial cancer were identified and proved to be non-coding RNAs. They were more effective ceRNAs associated with the miR-205-5p-PTEN network. CONCLUSION: Our results suggest that lncRNAs harbor MREs (miRNA response elements) and play important roles in the post-transcriptional regulation in EC. PMID- 26807191 TI - Effects of acute or chronic administration of novel 3,4-dimethoxyphenylethylamine derivates on anxiety-like behavior. AB - Novel anxiolytic medications are necessary to broaden treatment therapy. Thus, the aim of the present study was to compare the clinically effective anxiolytic, diazepam with the novel 3,4-dimethoxyphenylethylamine derivates. The novel 3,4 dimethoxyphenylethylamine derivates (PK, 0.1, 1.0, 10.0 mg/kg, i.p.) and diazepam (1.0 mg/kg) were injected acutely or chronically in animals subjected to the black-white model and the open field test. The acute administration of PK-2122 (0.1 mg/kg, i.p.) exerted anxiogenic-like effect, while in the middle or high doses PK-2122 exerted anxiolytic-like effect compared with the control group (p<0.05). The repeated treatment with PK-2111 was followed by anxiolytic-like effect in doses of 0.1 or 1.0 mg/kg which was more significant compared not only with control group, but with comparison to group treated with diazepam (p<0.05). Chronic treatment with PK-2123 or PK-2122 in all tested doses produced anxiolytic like effect (p<0.05), compared with control group and diazepam group. These results demonstrate that PK-2126, but not PK-2122, is dose independent and may be effective in experimental model of anxiety in rats when administered acutely or repeatedly. PMID- 26807190 TI - A SILAC-based proteomics elicits the molecular interactome of alisertib (MLN8237) in human erythroleukemia K562 cells. AB - Alisertib (MLN8237, ALS), an Aurora kinase A (AURKA) inhibitor, exerts potent anti-tumor effects in the treatment of solid tumor and hematologic malignancies in preclinical and clinical studies. However, the fully spectrum of molecular targets of ALS and its anticancer effect in the treatment of chronic myeloid leukemia (CML) are not clear. This study aimed to examine the proteomic responses to ALS treatment and unveil the molecular interactome and possible mechanisms for its anticancer effect in K562 cells using stable-isotope labeling by amino acids in cell culture (SILAC) approach. The proteomic data identified that ALS treatment modulated the expression of 1541 protein molecules (570 up; 971 down). The pathway analysis showed that 299 signaling pathways and 459 cellular functional proteins directly responded to ALS treatment in K562 cells. These targeted molecules and signaling pathways were mainly involved in cell growth and proliferation, cell metabolism, and cell survival and death. Subsequently, the effects of ALS on cell cycle distribution, apoptosis, and autophagy were verified. The flow cytometric analysis showed that ALS significantly induced G2/M phase arrest and the Western blotting assays showed that ALS induced apoptosis via mitochondria-dependent pathway and promoted autophagy with the involvement of PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways in K562 cells. Collectively, this study provides a clue to quantitatively evaluate the proteomic responses to ALS and assists in globally identifying the potential molecular targets and elucidating the underlying mechanisms of ALS for CML treatment, which may help develop new efficacious and safe therapies for CML treatment. PMID- 26807192 TI - Catalpol induces oligodendrocyte precursor cell-mediated remyelination in vitro. AB - In demyelinating diseases such as multiple sclerosis, one of the treatment strategies includes remyelination using oligodendrocyte precursor cells (OPC). Catalpol, the extract of radix rehmanniae, is neuroprotective. Using an OPC culture model, we showed that 10 MUM catalpol promotes OPC proliferation, cell migration and differentiation into mature oligodendrocytes. The 10 MUM catalpol displayed stronger effects on OPCs migration and oligodendrocyte differentiation. These results suggest that catalpol has a potential role in promoting remyelination in demyelinating diseases, and is of therapeutic interest. PMID- 26807193 TI - Chromophobe renal cell carcinoma with and without sarcomatoid change: a clinicopathological, comparative genomic hybridization, and whole-exome sequencing study. AB - Chromophobe renal cell carcinomas (CRCC) with and without sarcomatoid change have different outcomes; however, fewstudies have compared their genetic profiles. Therefore, we identified the genomic alterationsin CRCC common type (CRCC C) (n=8) and CRCC with sarcomatoid change (CRCC S) (n=4) using comparative genomic hybridization (CGH) and whole-exome sequencing. The CGH profiles showed that the CRCC C group had more chromosomal losses (72 vs. 18) but fewer chromosomal gains (23 vs. 57) than the CRCC S group. Losses of chromosomes 1p, 8p21-23, 10p16-20, 10p12-ter, 13p20-30, and 17p13 and gains of chromosomes 1q11, 1q21-23, 1p13-15, 2p23-24, and 3p21-ter differed between the groups. Whole-exome sequencing showed that the mutational status of 270 genes differed between CRCC (n=12) and normal renal tissues (n=18). In the functional enrichment analysis, the missense-mutated genes were classified into 6 biological processes (38 functions) and 5 pathways. The biological processes included cell adhesion, cell motility, ATP metabolism, sensory perception, carbohydrate and lipid metabolism and transport. The pathways included ATP-binding cassette transporter, extracellular matrix-receptor interaction, olfactory transduction, chondroitin sulfate biosynthesis, and hypertrophic cardiomyopathy. Whole-exome sequencing analysis revealed that the missense mutation statuses of 49 genes differed between the CRCC C and CRCC S groups. Furthermore, genetic alterations in metastasis suppressor 1, serine peptidase inhibitor Kazal type 8, transient receptor potential cation channel super family M member 6, Rh family B glycoprotein, and mannose receptor C type 1 were located in different chromosomal regions. These alterations may provide clues regarding CRCC tumorigenesis and provide a basis for future targeted therapies. PMID- 26807194 TI - A non-invasive miRNA based assay to detect bladder cancer in cell-free urine. AB - RNA from cell-free urine was analyzed in an attempt to identify a microRNA (miRNA) profile that could be used as a non-invasive diagnostic assay to detect the presence of urothelial carcinoma of the bladder (UCB) and provide a discriminatory signature for different stages of progression. In addition, the presence of specific miRNAs co-isolating with urinary extracellular vesicles/exosomes was investigated. RNA was isolated from cell-free urine of patients diagnosed with UCB (TaG1, T1G3, >=T2, CIS) and control patients (healthy control and UCB patients with no evidence of disease). MiRNAs were profiled by qRT-PCR array on pooled samples within each group. Validation of the miRNAs was performed on individual samples using qRT-PCR. Extracellular vesicles were isolated via ultracentrifugation. 236 miRNAs were detected in at least one of the pooled samples. Seven of the miRNAs validated on individual samples had significantly higher levels in the cancer group. A panel of miRNAs discriminated between cancer and cancer-free patients with a sensitivity of 88% and specificity of 78%, (AUC=88.8%). We recorded a sensitivity of 80% for TaG1, 95% for T1G3, 90% for >=T2 with specificity of 77% for healthy controls and 80% for no evidence of disease. Select miRNAs were detected in extracellular vesicles of UCB patients and healthy controls, albeit at different levels. Utilizing this non-invasive assay, we identified miRNA capable of detecting UCB and distinguishing different stages of progression, providing evidence that miRNA profiling in cell-free urine holds promise for the development of valuable clinical diagnostic tools. PMID- 26807195 TI - Silybin-vitamin E-phospholipids complex reduces liver fibrosis in patients with chronic hepatitis C treated with pegylated interferon alpha and ribavirin. AB - Chronic hepatitis C is both a virologic and a fibrotic disease, with mortality resulting mainly from the complications of cirrhosis and HCC. The aim was to evaluate the impact on of supplementation with a new pharmaceutical complex of silybinvitamin E-phospholipids in patients with chronic hepatitis C treated with Pegylated-Interferon-alpha2b plus Ribavirin. In this prospective, randomized, placebo controlled, double blind clinical trial, 32 subjects with chronic hepatitis, received Pegylated-Interferon-alpha2b (1.5 mg/kg per week) plus Ribavirin and placebo, while 32 subjects received the same dosage of Pegylated Interferon-alpha2b plus Ribavirin plus association of Silybin 47 mg + vitamin E 15 mg + phospholipids 97 mg in two pill for 12 months. Serum levels of the following markers of liver fibrosis were evaluated: transforming growth factor beta, hyaluronic acid, metalloproteinase 2, amino-terminal pro-peptide of type III procollagen, tissue inhibitor of matrix metalloproteinase type I. The comparison between group A and group B showed a significant difference in ALT (P<0.001), and viremia (P<0.05) after 12 months; in TGF beta levels after 12 months and at follow up (P<0.05); in MMP-2 after 6 months (P<0.05); in PIIINP after 6, 12 months and at follow up (P<0.05); in TIMP-1 after 6, 12 months and at follow up (P<0.001). In conclusion, the supplementation with silybin-vitamin E phosholipids complex ameliorated the response to Peg-IFN plus RBV treatment and reduced serum levels of markers of liver fibrosis. The ameliorative effect of the complex maybe related to a direct effect on the activation of hepatic stellate cells, or mediated via antioxidants. PMID- 26807196 TI - miR-873 induces lung adenocarcinoma cell proliferation and migration by targeting SRCIN1. AB - microRNAs (miRNAs) are endogenously expressed, conserved and small noncoding RNA that regulate gene expression by the post-transcriptional level. In this study, we aim to examine the role of miR-873 in lung adenocarcinoma. We found that the expression of miR-873 was upregulated in four lung adenocarcinoma cell lines and tissues. In addition, the expression levels of SRCIN1 were inversely correlated with the expression levels of miR-873 in lung adenocarcinoma tissues. Furthermore, SRCIN1 was confirmed asthe direct target of miR-873 by luciferase reporter assay and Western blotting. Overexpression of miR-873 promoted the proliferation and migration of lung adenocarcinoma cells, while SRCIN1 upregulation inhibited their proliferation and migration. Restoration of SRCIN1 could significantly reverse the proliferation and migration promotion imposed by miR-873. In summary, this study reveals for the first time that miR-873 increase the lung adenocarcinoma cell proliferation and migration through directly inhibiting SRCIN1 expression. PMID- 26807197 TI - Genetic variants within the hTERT gene and the risk of colorectal cancer in Lynch syndrome. AB - Lynch syndrome is an inherited cancer-predisposing disorder caused by germline mutations in the DNA mismatch repair (MMR) genes but there is a high degree of variability in cancer risk observed among carriers, suggesting the existence of modifying factors. Our aim was to investigate variants within the hTERT gene as a potential colorectal cancer (CRC) risk modifier for MMR gene mutation carriers. We identified 1098 MMR gene mutation carriers (420 MLH1, 481 MSH2, 126 MSH6, 53 PMS2 and 18 EPCAM) from 330 families recruited from either family cancer clinics or population cancer registries of the Australasian Colorectal Cancer Family Registry between 1997 and 2012. Using weighted Cox regression after adjusting for ascertainment bias, we estimated associations between 23 SNPs within the hTERT gene and CRC risk. During 46,836 person-years observation, 392 (36%) carriers were diagnosed with CRC at a mean age of 42.2 (standard deviation 11.4) years. There was no evidence of association between any of the hTERT SNPs and CRC risk, overall and stratified by sex and MMR gene mutated, after adjustment for multiple testing. Our findings suggest no evidence for clinical utility of the SNPs within the hTERT gene in Lynch syndrome. PMID- 26807198 TI - The role of FLI-1-EWS, a fusion gene reciprocal to EWS-FLI-1, in Ewing sarcoma. AB - Ewing sarcoma is a cancer of bone and soft tissue in children that is characterized by a chromosomal translocation involving EWS and an Ets family transcription factor, most commonly FLI-1. The EWS-FLI-1 fusion oncogene is widely believed to play a central role in Ewing sarcoma. The EWS-FLI-1 gene product regulates the expression of a number of genes important for cancer progression, can transform mouse cells such as NIH3T3 and C3H10T1/2, and is necessary for proliferation and tumorigenicity of Ewing sarcoma cells, suggesting that EWS-FLI-1 is the causative oncogene. However, a variety of evidence also suggest that EWS-FLI-1 alone cannot fully explain the Ewing sarcomagenesis. Here we report that FLI-1-EWS, a fusion gene reciprocal to EWS-FLI-1, is frequently expressed in Ewing sarcoma. We present evidence suggesting that endogenous FLI-1 EWS is required for Ewing sarcoma growth and that FLI-1-EWS cooperates with EWS FLI-1 in human mesenchymal stem cells, putative cells of origin of Ewing sarcoma, through abrogation of the proliferation arrest induced by EWS- FLI-1. PMID- 26807199 TI - Multiple myeloma cell lines and primary tumors proteoma: protein biosynthesis and immune system as potential therapeutic targets. AB - Despite great advance in multiple myeloma (MM) treatment since 2000s, it is still an incurable disease and novel therapies are welcome. Therefore, the purpose of this study was to explore MM plasma cells' (MM-PC) proteome, in comparison with their normal counterparts (derived from palatine tonsils of normal donors, ND PC), in order to find potential therapeutic targets expressed on the surface of these cells. We also aimed to evaluate the proteome of MM cell lines with different genetic alterations, to confirm findings obtained with primary tumor cells. Bone marrow (BM) samples from eight new cases of MM and palatine tonsils from seven unmatched controls were submitted to PC separation and, in addition to two MM cell lines (U266, RPMI-8226), were submitted to protein extraction for mass spectrometry analyses. A total of 81 proteins were differentially expressed between MM-PC and ND-PC - 72 upregulated and nine downregulated; U266 vs. RPMI 8226 cell lines presented 61 differentially expressed proteins - 51 upregulated and 10 downregulated. On primary tumors, bioinformatics analyses highlighted upregulation of protein biosynthesis machinery, as well as downregulation of immune response components, such as MHC class I and II, and complement receptors. We also provided comprehensive information about U266 and RPMI-8226 cell lines' proteome and could confirm some patients' findings. PMID- 26807200 TI - Distinct cholesterogenic and lipidogenic gene expression patterns in ovarian cancer - a new pool of biomarkers. AB - Cancer cells display different metabolic requirements compared to nonmalignant cells imposed by their need for rapid proliferation. Alterations in cellular metabolic pathways of lipid and cholesterol synthesis have been linked to tumorigenesis and cancer progression but have not been exploited in clinical diagnosis. Here, the expression of genes related to cholesterol/lipid metabolism was measured with semiquantitative and real-time RT-PCR in RNA isolated from normal, benign and cancer ovarian tissues. We found that both SREBF2 and its target gene DHCR7 are downregulated in ovarian cancer tissues. On the contrary, SREBF1c and its target SCD1 were upregulated. The steroidogenesis regulator PDE8B was found downregulated. Oncomine analysis supported these findings, and further revealed that in ovarian cancers, the SREBF1-regulated lipidogenic pathway is activated while the SREBF2-regulated cholesterogenic pathway is repressed based on expression profiles of HMGCR and DHCR7. In conclusion, we show that ovarian cancer cells display distinct lipidogenic and cholesterogenic gene expression profiles with potential applications in the development of new biomarkers and/or treatment of ovarian cancer. Reduced cholesterol and enhanced lipid synthesis and SCD1 expression may provide an explanation for the previously reported increased membrane fluidity of ovarian cancer cells, a finding that merits further investigation. PMID- 26807201 TI - Tumor cell expression of MMP3 as a prognostic factor for poor survival in pancreatic, pulmonary, and mammary carcinoma. AB - Breast, lung, and pancreatic cancers collectively represent one third of all diagnosed tumors and are responsible for almost 40% of overall cancer mortality. Despite improvements in current treatments, efforts to develop more specific therapeutic options are warranted. Here we identify matrix metalloproteinase 3 (MMP3) as a potential target within all three of these tumor types. MMP3 has previously been shown to induce expression of Rac1b, a tumorigenic splice isoform of Rac1. In this study we find that MMP3 and Rac1b proteins are both strongly expressed by the tumor cells of all three tumor types and that expression of MMP3 protein is prognostic of poor survival in pancreatic cancer patients. We also find that MMP3 gene expression can serve as a prognostic marker for patient survival in breast and lung cancer. These results suggest an oncogenic MMP3-Rac1b signaling axis as a driver of tumor progression in three common poor prognosis tumor types, further suggesting that new therapies to target these pathways could have substantial therapeutic benefit. PMID- 26807202 TI - High expression of cellular retinol binding protein-1 in lung adenocarcinoma is associated with poor prognosis. AB - PURPOSE: Adenocarcinoma, the most common non-small cell lung cancer is a leading cause of death worldwide, with a low overall survival (OS) despite increasing attempts to achieve an early diagnosis and accomplish surgical and multimodality treatment strategies. Cellular retinol binding protein-1 (CRBP-1) regulates retinol bioavailability and cell differentiation, but its role in lung cancerogenesis remains uncertain. EXPERIMENTAL DESIGN: CRBP-1 expression, clinical outcome and other prognostic factors were investigated in 167 lung adenocarcinoma patients. CRBP-1 expression was evaluated by immunohistochemistry of tissue microarray sections, gene copy number analysis and tumor methylation specific PCR. Effects of CRBP-1 expression on proliferation/apoptosis gene array, protein and transcripts were investigated in transfected A549 lung adenocarcinoma cells. RESULTS: CRBP-1(High) expression was observed in 62.3% of adenocarcinomas and correlated with increased tumor grade and reduced OS as an independent prognostic factor. CRBP-1 gene copy gain also associated with tumor CRBP-1(High) status and dedifferentiation. CRBP-1-transfected (CRBP-1(+)) A549 grew more than CRBP-1(-) A549 cells. At >1MUM concentrations, all trans-retinoic acid and retinol reduced viability more in CRBP-1(+) than in CRBP-1(-) A549 cells. CRBP 1(+) A549 cells showed up-regulated RARalpha/ RXRalpha and proliferative and transcriptional genes including pAkt, pEGFR, pErk1/2, creb1 and c-jun, whereas RARbeta and p53 were strongly down-regulated; pAkt/pErk/ pEGFR inhibitors counteracted proliferative advantage and increased RARalpha/RXRalpha, c-jun and CD44 expression in CRBP-1(+) A549 cells. CONCLUSION: CRBP-1(High) expression in lung adenocarcinoma correlated with increased tumor grade and reduced OS, likely through increased Akt/Erk/EGFR-mediated cell proliferation and differentiation. CRBP-1(High) expression can be considered an additional marker of poor prognosis in lung adenocarcinoma patients. PMID- 26807203 TI - MEK inhibition induces apoptosis in osteosarcoma cells with constitutive ERK1/2 phosphorylation. AB - Conventional high-grade osteosarcoma is the most common primary bone cancer with relatively high incidence in young people. Recurrent and metastatic tumors are difficult to treat. We performed a kinase inhibitor screen in two osteosarcoma cell lines, which identified MEK1/2 inhibitors. These inhibitors were further validated in a panel of six osteosarcoma cell lines. Western blot analysis was performed to assess ERK activity and efficacy of MEK inhibition. A 3D culture system was used to validate results from 2D monolayer cultures. Gene expression analysis was performed to identify differentially expressed gene signatures in sensitive and resistant cell lines. Activation of the AKT signaling network was explored using Western blot and pharmacological inhibition. In the screen, Trametinib, AZD8330 and TAK-733 decreased cell viability by more than 50%. Validation in six osteosarcoma cell lines identified three cell lines as resistant and three as sensitive to the inhibitors. Western blot analysis of ERK activity revealed that sensitive lines had high constitutive ERK activity. Treatment with the three MEK inhibitors in a 3D culture system validated efficacy in inhibition of osteosarcoma viability. MEK1/2 inhibition represents a candidate treatment strategy for osteosarcomas displaying high MEK activity as determined by ERK phosphorylation status. PMID- 26807204 TI - Hepatitis C virus infection and thyroid autoimmune disorders: A model of interactions between the host and the environment. AB - The hepatitis C virus (HCV) infection is an important public health problem and it is associated with hepatic and extrahepatic manifestations. Autoimmune thyroid diseases are common in HCV infected patients and the standard interferon-based treatment is associated with an increase of the immune-mediated thyroid damage. Recent evidence in the literature analyzed critical points of the mechanisms of thyroid damage, focusing on the balance between the two sides of the interaction: The environment (virus infection with potential cross-reaction) and the host (susceptibility genes with consistent immune response). The spectrum of antiviral treatment for chronic HCV infection is rapidly expanding for the development of dual o triple therapy. The availability of interferon-free combined treatment with direct antiviral agents for HCV is very promising, in order to ameliorate the patient compliance and to reduce the development of thyroid autoimmunity. PMID- 26807205 TI - Chronic hepatitis C: This and the new era of treatment. AB - Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan genotypic drugs with high efficacy but without side effects. PMID- 26807206 TI - Hepatitis C virus and non-Hodgkin's lymphomas: Meta-analysis of epidemiology data and therapy options. AB - Hepatitis C virus (HCV) is a global health problem affecting a large fraction of the world's population: This virus is able to determine both hepatic and extrahepatic diseases. Mixed cryoglobulinemia, a B-cell "benign" lymphoproliferative disorders, represents the most closely related as well as the most investigated HCV-related extrahepatic disorder. Since this virus is able to determine extrahepatic [non-Hodgkin's lymphoma (NHL)] as well as hepatic malignancies (hepatocellular carcinoma), HCV has been included among human cancer viruses. The most common histological types of HCV-associated NHL are the marginal zone, the lymphoplasmacytic and diffuse large cell lymphomas. The role of the HCV in the pathogenesis of the B-cell lymphoproliferative disorders is confirmed also by the responsiveness of the NHL to antiviral therapy. The purpose of this review is to provide an overview of the recent literature and a meta analysis of the epidemiology data, to explain the role of HCV in the development of NHL's lymphoma. Furthermore, the possibility to treat these HCV-related NHL with the antiviral therapy or with other therapeutic options, like chemotherapy, is also discussed. PMID- 26807207 TI - Hepatitis E virus infection in the liver transplant recipients: Clinical presentation and management. AB - Hepatitis E virus (HEV) is an emerging pathogen and an increasingly recognized cause of graft hepatitis, especially in the post-orthotopic liver transplantation immunocompromised population. The exact incidence and prevalence of HEV infection in this population remains unclear but is certainly greater than historical estimates. Identifying acute HEV infection in this population is imperative for choosing the right course of management as it is very difficult to distinguish histologically from acute rejection on liver biopsy. Current suggested approach to manage acute HEV involves modifying immunosuppression, especially discontinuing calcineurin inhibitors which are the preferred immunosuppressive agents post-orthotopic liver transplantation. The addition of ribavirin monotherapy has shown promising success rates in clearing HEV infection and is used commonly in reported cases. PMID- 26807208 TI - Ribavirin: Past, present and future. AB - Before the advent of direct acting antiviral agents (DAAs) ribavirin, associated to pegylated-interferon played a crucial role in the treatment of chronic hepatitis C, preventing relapses and breakthroughs. In the present era of new potent DAAs, a place is still devoted to the drug. Ribavirin associated with sofosbuvir alone is efficient in the treatment of most cases of G2 infected patients. All options currently available for the last difficult-to-treat cirrhotic G3 patients contain ribavirin. Reducing treatment duration to 12 wk in G1 or G4 cirrhotic compensated patients is feasible thanks to ribavirin. Retreating patients with acquired anti NS5A resistance-associated variants using ribavirin-based strategies could be useful. The addition of ribavirin with DAAs combinations however, leads to more frequent but mild adverse events especially in cirrhotic patients. Preliminary data with interferon-free second generation DAAs combinations without ribavirin suggest that future of the drug is jeopardized even in difficult-to-treat patients: The optimization of ribavirin dosage according to an early monitoring of blood levels has been suggested to be relevant in double therapy with peginterferon or sofosbuvir but not with very potent combinations of more than two DAAs. PMID- 26807210 TI - Identification of Differentially Expressed miRNAs in Appendiceal Mucinous Cystadenocarcinoma from Mucinous Cystadenoma. AB - OBJECTIVE: Mucinous cystadenocarcinoma of appendix is a rare entity. Differentiating mucinous cystadenocarcinoma from mucinous cystadenoma is very challenging and depends on establishing the presence of malignant cells in the appendix wall. The invasion may be very difficult to assess in some cases, especially in early stages of the disease, which could have devastating prognostic effects on patients. Therefore, it is necessary to develop an ancillary test that can differentiate the mucinous cystadenocarcinoma from mucinous cystadenoma. So far, there is no report available about the role of differentially expressed miRNAs in the diagnosis of appendiceal mucinous cystadenocarcinoma. MATERIALS AND METHODS: Six confirmed mucinous appendiceal cystadenocarcinoma and twelve mucinous appendiceal cystadenoma cases were selected. The total RNAs were extracted from the formalin-fixed paraffin-embedded specimen of these cases. The comprehensive miRNA microarray expression profiling from pooled aliquots of RNA samples from these two entities were analyzed to detect the differentially expressed miRNAs in mucinous cystadenocarcinoma. The best seven differentially expressed miRNAs were validated in individual cases by quantitative reverse transcriptase PCR (qRT-PCR). RESULTS: The microarray miRNA expression profiling analysis revealed 646 miRNAs that were differentially expressed in the mucinous cystadenocarcinoma. Among these differentially expressed miRNAs, the expression of 80 miRNAs showed statistical difference (p<0.01). The quantitative RT-PCR validated that the expression of miR-1, miR 4328 was significantly down regulated in mucinous cystadenocarcinoma compared to the mucinous cystadenoma (p<0.05). On the other hand, the expression of miR-200b, miR-200c, miR-451, miR-223 and miR-21 were significantly upregulated in mucinous cystadenocarcinoma (p<0.05). CONCLUSION: The expression levels of miRNAs tested were significantly altered in the appendiceal mucinous cystadenocarcinoma samples compared to the mucinous cystadenoma. These data suggest that the miRNA expression in mucinous appendiceal neoplasm may help to supplement the morphological evaluation in distinguishing benign from malignant tumors. PMID- 26807209 TI - Hepatitis C and insulin action: An intimate relationship. AB - Chronic hepatitis C virus (HCV) infection has been shown to be linked to a higher prevalence of type 2 diabetes compared with the general population or with patients with chronic hepatitis B infection and diabetes is the most common extra hepatic manifestation of HCV. The HCV-diabetes association is due to insulin resistance (IR) that occurs early in the course of the disease even in patients without or with minimal fibrosis. The mechanisms for HCV-induced IR are only partly understood and include a direct inhibitory effect of HCV on insulin signaling pathway. IR in chronic HCV results in an increased progression rate of hepatic fibrosis, cirrhosis and hepatocellular carcinoma. Some but not all studies found that IR reduces the response rate to interferon/ribavirin therapy. Whether IR affects the response to the new direct-acting antiviral treatments is still unknown. PMID- 26807212 TI - Preclinical studies of sex differences: a clinical perspective. AB - The new policy from the National Institutes of Health to encourage grant applicants to consider studying both females and males in preclinical biological experiments has been met with support and opposition. Here, we will discuss implications of preclinical studies of sex differences on clinical research. PMID- 26807211 TI - Iron(II)-catalyzed asymmetric intramolecular olefin aminochlorination using chloride ion. AB - An iron-catalyzed enantioselective and diastereoselective intramolecular olefin aminochlorination reaction is reported (ee up to 92%, dr up to 15 : 1). In this reaction, a functionalized hydroxylamine and chloride ion are utilized as nitrogen and chlorine sources, respectively. This new method tolerates a range of synthetically valuable internal olefins that are all incompatible with existing asymmetric olefin aminochlorination methods. PMID- 26807213 TI - What proportion of adult allergy referrals to secondary care could be dealt with in primary care by a GP with special interest? AB - BACKGROUND: The concept of a General Practitioner with Special Interest (GPwSI) was first proposed in the 2000 National Health Service Plan, as a way of providing specialised treatment closer to the patient's home and reducing hospital waiting times. Given the patchy and inadequate provision of allergy services in the UK the introduction of GPwSIs might reduce the pressure on existing specialist services. OBJECTIVES: This study assessed what proportion of referrals to a specialist allergy clinic could be managed in a GPwSI allergy service with a predefined range of facilities and expertise (accurate diagnosis and management of allergy; skin prick testing; provision of advice on allergen avoidance; ability to assess suitability for desensitisation). METHODS: 100 consecutive GP referrals to a hospital allergy clinic were reviewed to determine whether patients could be seen in a community-based clinic led by a general practitioner with special interest (GPwSI) allergy. The documentation relating to each referral was independently assessed by three allergy specialists. The referrals were judged initially on the referral letter alone and then re-assessed with the benefit of information summarised in the clinic letter, to determine whether appropriate triage decisions could be made prospectively. The proportion of referrals suitable for a GPwSI was calculated and their referral characteristics identified. RESULTS: 29 % referrals were judged unanimously appropriate for management by a GPwSI and an additional 30 % by 2 of the 3 reviewers. 18 % referrals were unsuitable for a GPwSI service because of the complexity of the presenting problem, patient co-morbidity or the need for specialist knowledge or facilities. CONCLUSIONS AND CLINICAL RELEVANCE: At least a quarter, and possibly half, of allergy referrals to our hospital-based service could be dealt with in a GPwSI clinic, thereby diversifying the patient pathway, allowing specialist services to focus on more complex cases and reducing the waiting time for first appointments. PMID- 26807214 TI - A case report of Mycoplasma wenyonii associated immune-mediated haemolytic anaemia in a dairy cow. AB - BACKGROUND AND CASE PRESENTATION: A three year old, second lactation Holstein dairy cow presented to the Scottish Centre for Production Animal Health and Food Safety, Glasgow University Veterinary School in November 2014 with a history of post-calving vulval/vaginal bleeding nine days prior to presentation, followed by a sudden reduction in milk yield. Subsequent investigations resulted in a diagnosis of immune-mediated haemolytic anaemia secondary to infection with Mycoplasma wenyonii. CONCLUSION: This report of a novel presentation of Mycoplasma wenyonii in a dairy cow illustrates the need to consider M.wenyonii as a potential differential diagnosis when a cow presents with anaemia and will discuss the potential implications of the condition at herd-level. PMID- 26807215 TI - Effect of dietary canthaxanthin and 25-hydroxycholecalciferol supplementation on the performance of duck breeders under two different vitamin regimens. AB - BACKGROUND: Dietary canthaxanthin (CX), 25-hydroxycholecalciferol (25-OH-D 3 ) and vitamins have been widely reported to be involved in productive and reproductive performance of broiler breeders. However, limited information is available for duck breeders. In this study, a total of 1,560 Cherry Valley SM3 duck breeder females and 312 males were used to assess if the addition of CX and 25-OH-D3 could increase the performance of duck breeders under two different dietary vitamin regimens. Four diets were used under a 2 * 2 factorial arrangement with 2 kinds of vitamin premixes (REGULAR and HIGH; HIGH premix had higher levels of all vitamins except K3 than REGULAR premix), and with or without the supplementation of the mixture of CX (6 mg/kg) and 25-OH-D3 (0.069 mg/kg). The ducks were fed ad libitum with pelleted diets based on corn-soybean meal from 38 to 77 wk of age. RESULTS: HIGH vitamin premix decreased malondialdehyde (MDA) level (P < 0.001) of egg yolk, increased hatchability of fertile eggs (P = 0.029), increased hatchability of total eggs (P = 0.029), and decreased serum protein carbonyl level (P = 0.037) of breeder males. The mixture of CX and 25-OH D3 increased serum calcium of breeder females (P = 0.010), decreased the cracked egg rate (P = 0.001), increased the pigmentation of egg yolk (P < 0.001) and male bill (P < 0.001), and decreased MDA level of egg yolk (P < 0.001) and male serum (P = 0.034). Interactive effects were observed in cracked egg rate (P = 0.038), shell thickness (P = 0.011) and serum phosphorus (P = 0.026) of breeder females. HIGH vitamin premix together with the mixture of CX and 25-OH-D3 decreased cracked egg rate and increased shell thickness of duck breeders. Serum phosphorus was decreased in duck breeder females fed REGULAR vitamin premix without the addition of the CX and 25-OH-D3 mixture. CONCLUSIONS: Dietary HIGH vitamin premix increased antioxidant status of eggs and breeder males, and increased hatchability. The mixture of CX and 25-OH-D3 enhanced egg shell quality, and promoted pigmentation and antioxidant status of eggs and breeder males. PMID- 26807216 TI - Prevalence of using non prescribed medications in economically deprived rural population of Pakistan. AB - BACKGROUND: Self medication is described as an act of procurement and consumption of medical drugs without the advice of medical physician for diagnosis, prescription and surveillance of treatment. There is a paucity of literature with regards to self medication among rural dwellers of Pakistan and no initiatives have been taken to resolve this issue. Therefore, the study aimed to evaluate frequency, practice and prevalence of self medication among economically deprived rural population of Karachi (South Pakistan). METHODS: This was the descriptive, epidemiological cross sectional survey which was conducted at the two largest tertiary care government based teaching hospitals of Karachi, Civil hospital and Jinnah Postgraduate Medical Centre, from January 2015 until March 2015. Seven hundred rural dwellers were recruited; who were the residents of outskirts of Karachi city were enrolled in the above mentioned period through the outpatient department (OPD) of the respective hospitals. RESULTS: According to the survey, 595 (85 %) subjects practiced self medication. The most common reasons evaluated for self medication were cost of consultation (90.3 %) and availability of transport (81.0 %) from rural area to health care facility. The paracetamol as a painkiller (93.0 %), acetylsalicylic acid as an anti pyretic (69.0 %), anti biotic (52.0 %) and anti allergic (51.0 %) were the commonest drug used without prescription of a health care physician. A significant difference was obtained in carrying out self medication between participants earning less than 50,000 PKR and greater than this amount (p = 0.029; 61 % vs. 24 %) and for the self medicated patients having education less than graduation with the participants having education of graduation or above it (p = 0.03; 63 % vs. 22 %). CONCLUSION: The self medication among rural dwellers of Karachi is high . As a result, urgent steps must be taken to initiate the awareness and educational programs regarding potential risks of self medication. Secondly, strict measures must be introduced to stop supply of prescription drugs from pharmacies without prescription. Thirdly, provision of cost effective treatment from public sector hospitals to rural population can help to reduce self medication among rural population of Pakistan. PMID- 26807217 TI - Validity and reliability of a modified english version of the physical activity questionnaire for adolescents. AB - BACKGROUND: Adaptation of physical activity self-report questionnaires is sometimes required to reflect the activity behaviours of diverse populations. The processes used to modify self-report questionnaires though are typically underreported. This two-phased study used a formative approach to investigate the validity and reliability of the Physical Activity Questionnaire for Adolescents (PAQ-A) in English youth. Phase one examined test content and response process validity and subsequently informed a modified version of the PAQ-A. Phase two assessed the validity and reliability of the modified PAQ-A. METHODS: In phase one, focus groups (n = 5) were conducted with adolescents (n = 20) to investigate test content and response processes of the original PAQ-A. Based on evidence gathered in phase one, a modified version of the questionnaire was administered to participants (n = 169, 14.5 +/- 1.7 years) in phase two. Internal consistency and test-retest reliability were assessed using Cronbach's alpha and intra-class correlations, respectively. Spearman correlations were used to assess associations between modified PAQ-A scores and accelerometer-derived physical activity, self-reported fitness and physical activity self-efficacy. RESULTS: Phase one revealed that the original PAQ-A was unrepresentative for English youth and that item comprehension varied. Contextual and population/cultural-specific modifications were made to the PAQ-A for use in the subsequent phase. In phase two, modified PAQ-A scores had acceptable internal consistency (alpha = 0.72) and test-retest reliability (ICC = 0.78). Modified PAQ-A scores were significantly associated with objectively assessed moderate-to-vigorous physical activity (r = 0.39), total physical activity (r = 0.42), self-reported fitness (r = 0.35), and physical activity self-efficacy (r = 0.32) (p <= 0.01). CONCLUSIONS: The modified PAQ-A had acceptable internal consistency and test-retest reliability. Modified PAQ-A scores displayed weak-to-moderate correlations with objectively measured physical activity, self-reported fitness, and self-efficacy providing evidence of satisfactory criterion and construct validity, respectively. Further testing with more diverse English samples is recommended to provide a more complete assessment of the tool. PMID- 26807218 TI - Particulate matters from diesel heavy duty trucks exhaust versus cigarettes emissions: a new educational antismoking instrument. AB - BACKGROUND: Indoor smoking in public places and workplaces is forbidden in Italy since 2003, but some health concerns are arising from outdoor secondhand smoke (SHS) exposure for non-smokers. One of the biggest Italian Steel Manufacturer, with several factories in Italy and abroad, the Marcegaglia Group, recently introduced the outdoor smoking ban within the perimeter of all their factories. In order to encourage their smoker employees to quit, the Marcegaglia management decided to set up an educational framework by measuring the PM1, PM2.5 and PM10 emissions from heavy duty trucks and to compare them with the emissions of cigarettes in an indoor controlled environment under the same conditions. METHODS: The exhaust pipe of two trucks powered by a diesel engine of about 13.000/14.000 cc(3) were connected with a flexible hose to a hole in the window of a container of 36 m(3) volume used as field office. The trucks operated idling for 8 min and then, after adequate office ventilation, a smoker smoked a cigarette. Particulate matter emission was thereafter analyzed. RESULTS: Cigarette pollution was much higher than the heavy duty truck one. Mean of the two tests was: PM1 truck 125.0(47.0), cigarettes 231.7(90.9) p = 0.002; PM2.5 truck 250.8(98.7), cigarettes 591.8(306.1) p = 0.006; PM10 truck 255.8(52.4), cigarettes 624.0(321.6) p = 0.002. CONCLUSIONS: Our findings may be important for policies that aim reducing outdoor SHS exposure. They may also help smokers to quit tobacco dependence by giving them an educational perspective that rebuts the common alibi that traffic pollution is more dangerous than cigarettes pollution. PMID- 26807219 TI - Advantages of the avian model for human ovarian cancer. AB - Ovarian cancer (OC) is the most lethal gynecological cancer. Early detection of OC is crucial for providing efficient treatment, whereas high mortality rates correlate with late detection of OC, when the tumor has already metastasized to other organs. The most prevalent type of OC is epithelial OC (EOC). Models that have been used to study EOC include the fruit fly, mouse and laying hen, in addition to human EOC cells in 3D culture in vitro. These models have helped in the elucidation of the genetic component of this disease and the development of drug therapies. However, the histological origin of EOC and early markers of the disease remain largely unknown. In this study, we aimed to review the relative value of each of the different models in EOC and their contributions to understanding this disease. It was concluded that the spontaneous occurrence of EOC in the adult hen, the prolific ovulation, the similarity of metastatic progression with that in humans and the advantages of using the chicken embryo for modelling the development of the reproductive system, renders the hen particularly suitable for studying the early development of EOC. Further investigation of this avian model may contribute to a better understanding of EOC, improve clinical insight and ultimately contribute to decreasing its mortality rates among humans. PMID- 26807220 TI - Reasons for cancer metastasis: A holistic perspective. AB - Over several years, scientists investigating cancer have focused their efforts on elucidating the mechanisms underlying cancer metastasis, with the aim of finding a way to inhibit this process. These mechanisms, however, only explain the process of cancer metastasis, but do not explain why cancer would metastasize in the first place. Cancer metastasizes due to several factors, namely attack by the immune system, lack of oxygen and necessary nutrients, large amounts of lactic acid produced by glycolysis and increased cell death. Therefore, the majority of the presently available treatments for cancer also bear the potential to induce metastasis. Thus, it is crucial in medical practice to minimize the risk of cancer metastasis during a time when there are no effective means to inhibit this process. PMID- 26807221 TI - Roles of sex-determining region Y-box 2 in cell pluripotency and tumor-related signaling pathways. AB - The sex-determining region Y-box 2 (SOX2) gene, a member of the Sry-like high mobility group box (SOX) gene family, encodes the transcription factor Sox2, which significantly contributes to the regulation of cell pluripotency. Sox2 is closely associated with early embryonic development, neural differentiation and other biological processes. An inreasing number of recent studies suggest that Sox2 exerts a positive effect on malignant tumors. According to these results, Sox2 is expected to become a novel target for cancer therapy by unveiling the mechanism through which it affects the biological behavior of tumors. Therefore, it is crucial to elucidate the detailed association of Sox2 with malignant tumors. The aim of this study was to review the role of Sox2 in pluripotency maintenance, early embryonic development and neural differentiation, as well as investigate the detailed mechanism through which Sox2 regulates cancer stem cells and tumorigenesis. PMID- 26807222 TI - Carboplatin-etoposide combination chemotherapy in metastatic castration-resistant prostate cancer: A retrospective study. AB - The combination of cisplatin or carboplatin and etoposide is the standard treatment for certain poorly differentiated neuroendocrine cancers, such as small cell lung cancer. The aim of this study was to assess the efficacy and tolerability of the carboplatin-etoposide regimen in metastatic castration resistant prostate cancer (mCRPC). A total of 27 patients treated by carboplatin [area under the curve (AUC)=5] and etoposide (100 mg/m2 intravenous infusion on days 1-3 or 75 mg orally/day for 10 days) for mCRPC were included for analysis. The median progression-free survival was 3.3 months [95% confidence interval (CI): 1.9-4.2] and the median overall survival (OS) was 8.1 months (95% CI: 4.06 12.36). The main grade 3-4 toxicities were haematological, namely anemia (33.3%), neutropenia (25.9%) and thrombocytopenia (22.2%), whereas the most common non hematological toxicity was asthenia (22.2%). The efficacy, compliance and safety profile were generally similar between the oral and intravenous etoposide groups. Pretreated patients with mCRPC may benefit from the carboplatin-etoposide regimen in terms of OS. The toxicities were acceptable, without reported treatment related mortality. Therefore, the oral etoposide regimen may be an viable alternative for improving the quality of life of the patients. However, this regimen requires further prospective investigation to confirm its efficacy. PMID- 26807223 TI - Upregulation of circulating cytokeratin 20, urokinase plasminogen activator and C reactive protein is associated with poor prognosis in gastric cancer. AB - Gastric cancer is one of the most common types of cancer, with a high mortality rate. The aim of this study was to investigate the role of several key molecules, including cytokeratin (CK) 19 and CK20, urokinase plasminogen activator (uPA), C reactive protein (CRP) and matrix metalloproteinase (MMP)-9, which are involved in cancer invasion and metastasis, in order to determine whether they may be considered as novel prognostic factors for gastric cancer. Peripheral blood was collected from 165 patients with gastric adenocarcinoma who underwent curative surgical resection at Zhejiang Cancer Hospital (Hangzhou, China) between 2010 and 2011. The mRNA levels of CK19, CK20, uPA and MMP-9 were detected by reverse transcription-quantitative polymerase chain reaction. The protein expression of CRP was measured by immunoturbidimetry. The Students t-test was used in the univariate analyses and the Kaplan-Meier method was used to analyze the survival curves. The relative mRNA expression of CK19 and MMP-9 was not found to be significantly associated with gender, age or cancer stage, whereas that of CK20 and uPA was associated with gastric cancer stage: The low-expression group was associated with early-stage and the high-expression group with more advanced stage disease (P<0.05). The CRP protein level was associated with gender and cancer stage: The low-expression group was predominantly associated with male gender and early-stage disease, whereas the high-expression group was associated with female gender and advanced-stage disease (P<0.05). The expression of CK19, CK20, uPA and CRP, but not MMP-9, was negatively associated with overall survival (OS): The OS rate in the high-expression groups was significantly lower compared with that in the low-expression groups (P<0.05). In conclusion, the upregulation of CK20, uPA and CRP was found to be a negative prognostic factor for gastric cancer. PMID- 26807224 TI - Resident training in single-incision laparoscopic colectomy. AB - Single-incision laparoscopic colectomy (SLC) is touted as an improved approach to minimally invasive surgery, although no data currently exist regarding the acquisition of this technique. The aim of this study was to evaluate resident performance and outcomes in patients undergoing SLC performed by residents vs. staff colorectal surgeons. A retrospective case-control study was conducted, including 220 patients who underwent elective surgical intervention with multiport laparoscopic colectomy (MLC, n=141) or SLC (n=79) for colon cancer over a 24-month period at Yao Municipal Hospital (Yao, Japan). Data on patient demographics, operative data, oncological outcomes and short-term outcomes were evaluated for statistical significance. To investigate issues regarding the surgical procedures, the entire operation was recorded on video for all patients and was divided into 6 procedures, with each procedure measured in seconds. Senior-level residents were able to safely perform MLC under appropriate experienced supervision. For SLC, 1 case required conversion to an open procedure. No case required additional trocar placement. The mean operative times were similar for the staff and resident groups for total colon cancer (192.5 and 217.5 min, respectively; P=0.88), whereas the operative times of the staff group for right-sided colon cancer were significantly longer, and the operative times of the resident group for left-sided colon cancer were significantly longer. In addition, the overall perioperative outcomes, including blood loss, number of harvested lymph nodes, length of the surgical margin and complications, were similar between the two groups. When video recordings were evaluated by dividing the surgical process for the right colon into 4 procedures and that for the left colon into 6 procedures, the results demonstrated that the residents required more time to close the mesenteric margin for the left colon compared with the staff performing the same procedure (3,470.1+/-1,258.5 vs. 5,218.6+/-2,341.2 sec; P=0.01). Therefore, senior-level residents were able to safely perform SLC under appropriate experienced supervision. For the left colon, the main challenge for the residents appeared to be the closure of the mesenteric margin. Our data support that it is possible to train senior residents to complete a SLC safely and with the same efficacy as staff surgeons. PMID- 26807225 TI - Role of CXC chemokine receptor type 7 in carcinogenesis and lymph node metastasis of colon cancer. AB - Upregulated expression of the CXC chemokine receptor type 7 (CXCR7) promotes breast, lung and prostate cancer progression and metastasis. However, the role of CXCR7 in colon cancer has not been determined. We hypothesized that increased CXCR7 expression may contribute to human colon cancer occurrence and progression. Reverse transcription quantitative polymerase chain reaction and western blot analysis were performed on 34 malignant and 18 normal colon tissue specimens. The specimens were obtained from 19 male and 15 female patients, with a mean age of 52 years (range, 34-79 years). Of the 34 patients, 20 had lymph node metastases. None of the patients had received adjuvant radiotherapy or chemotherapy prior to surgery. This study demonstrated that CXCR7 levels were significantly higher in colon tumors compared with those in normal colon tissue (P<0.01). In addition, lymph node metastatic colon tumors exhibited significantly higher CXCR7 expression compared with non-metastatic tumors (P<0.01); however, there were no differences in CXCR7 expression among distinct histopathological types (well differentiated vs. moderately-to-poorly differentiated adenocarcinoma, P>0.01). Therefore, the evidence obtained from the present study supports involvement of the upregulated CXCR7 expression in colon tumorigenesis and lymph node metastasis. PMID- 26807226 TI - Enhanced antitumor effect of combining chemotherapy with Epstein-Barr virus (EBV) specific cytotoxic T lymphocytes in mice with EBV-related non-Hodgkin's lymphoma. AB - Epstein-Barr virus (EBV)-related non-Hodgkin's lymphoma (NHL) represents a major problem in hematological clinical studies due to its drug tolerance and refractoriness. EBV infection is a key factor driving the process of tumor growth. Immune therapy is an important biotherapeutic method of treating cancer, which is attracting increasing attention. We hypothesized that combining conventional chemotherapy with immune therapy in the treatment of EBV-related NHL may achieve better outcomes. First, we successfully cloned large numbers of EBV specific T cells by immune stimulation ex vivo. Subsequently, the combined therapy was applied in a murine model of human EBV-related NHL. As expected, combined therapy inhibited tumor growth more effectively compared with monotherapy. In addition, we continuously tested the tumor-associated immune microenvironment and observed that the numbers of tumor-infiltrating cytotoxic T lymphocytes (CTLs) and macrophages were elevated following combined therapy. These effects suggest that EBV-specific CTLs may indirectly promote an innate immune reaction in lymphoma by activating tumor-infiltrating macrophage proliferation. Our findings may provide a guide for the prospective treatment of EBV-related NHL. PMID- 26807227 TI - Antiviral therapy improves the survival rate and decreases recurrences and fatalities in liver cancer patients following curative resection: A meta analysis. AB - The present study aimed to investigate the impact of postoperative antiviral treatment on tumor recurrence, fatalities and survival of patients with chronic hepatitis B virus (HBV) infection-related primary hepatocellular carcinoma (HCC). A systematic meta-analysis was performed. All the studies comparing nucleos(t)ide analogues (NAs) versus placebo or no treatment were considered. The results were expressed as relative ratio (RR) for 1-, 3- and 5-year recurrence-free survival (RFS) and overall survival (OS), recurrence HCC and fatalities with 95% confidence intervals (CI) using STATA 11.0. In total, 15 trials with 7,619 patients were included. There were significant improvements for 1-, 3- and 5-year RFS (RR, 1.09; P=0.003; RR, 1.202; P<0.001; and RR, 1.219; P=0.02; respectively) and in 3- and 5-year OS (RR, 1.087, P=0.006; and RR, 1.186; P<0.001) in the NAs group compared with the control group. Sensitivity analyses confirmed the robustness of the results. In addition, the significantly high rate of recurrence HCC and fatalities existed in the control group (RR, 1.301; P=0.002; and RR, 1.816, P<0.001). One study was for an entecavir (ETV)-treated group compared with an adefovir (ADV)-treated group and lamivudine (LAM)-treated group. The 3-year disease-free survival rate for the ETV group was significantly better compared with the ADV and LAM groups [hazard ratio (HR), 0.810; P=0.049; and HR, 0.737; P=0.007]. The present study demonstrated the beneficial effects of NAs therapy following curative treatment of HBV-related HCC. ETV may be the superior choice compared to ADV or LAM for the antiviral treatment. PMID- 26807228 TI - Radiation therapy following targeted therapy in oligometastatic renal cell carcinoma. AB - Up to 40% of patients with renal cell carcinoma (RCC) with initially localized disease eventually develop metastasis following nephrectomy. The current standard of care for metastatic RCC (mRCC) is targeted therapy. However, complete response remains rare. A state of oligometastatic disease may exist, in which metastases are present in a limited number of locations; such cases may benefit from metastasis-directed local therapy, based on the evidence supporting resection of limited-volume metastases, allowing for improved disease control. We retrospectively analyzed 7 cases of response of RCC metastases, in patients treated with targeted therapies followed by radiation therapy (RT) of residual metastatic lesions in Paoli-Calmettes Institute (Marseille, France). We analyzed disease response rates, response to sequential strategy, relapse at the irradiated locations and disease evolution. The median follow-up was 34.1 months (range, 19.2-54.5 months). No progression at the irradiated sites was observed. A total of 5 patients had stable disease at the irradiated locations at the last follow-up; 3 remained in complete remission at the assessment, and 2 were stable. Excellent local response and clinical benefit may be achieved without added toxicity. In conclusion, sequential therapeutic strategies with RT following systemic treatment using sunitinib appear to be highly effective in patients with progressive mRCC and prompt the conduction of further confirmatory trials. PMID- 26807229 TI - Microsurgical approach for unusual and unexpected malignant fibrous histiocytoma of the forearm: A case report. AB - Soft tissue sarcomas are rare tumors with a dismal prognosis. Among the most common histological types of sarcomas of the extremities, malignant fibrous histiocytoma (MFH) is the one with the highest incidence. Surgery is considered to be the first choice of treatment for MFH. To the best of our knowledge, this is the first case report in the literature of a patient with MFH within the abductor pollicis longus (APL) muscle. This unusual location was also unexpected by the treating surgeons, as the preoperative magnetic resonance imaging localized the tumor inside a different muscle. A 79-year-old Caucasian man presented with a swelling in the middle third of the dorsal aspect of the left forearm. MFH was diagnosed following biopsy and instrumental diagnostic examinations. Surgical excision and simultaneous reconstruction was performed by the same microsurgical team, achieving an excellent functional outcome. The present case highlights the significance of microsurgical approach for improving strategic planning in oncologic surgery. Accurate surgical dissection, performed by a team of microsurgeons, allowed for the identification of the unusual and unexpected tumor localization within the APL muscle. For this reason, a change of surgical strategy allowed for preservation of the extensor digitorum communis muscle, which would otherwise have to be resected, with tendon transfer and successful restoration of the thumb abduction function. PMID- 26807230 TI - Clinical significance of serum claudin-1 and claudin-7 levels in patients with colorectal cancer. AB - The present study aimed to investigate the serum levels and clinical relevance of claudin (CLDN) 1 and CLDN7 in patients with colorectal cancer (CRC). A total of 140 patients with a pathologically confirmed diagnosis of CRC were enrolled in this study. The serum levels of CLDN1 and CLDN7 were determined using the solid phase sandwich ELISA method. A total of 40 healthy age- and gender-matched controls were included in the analysis. The median age of the patients was 60 years (range, 24-84 years). The localization of the tumor in the majority of the patients was the colon (n=81, 58%). Of the 55 metastatic patients who received palliative chemotheraphy, 31% were chemotherapy-responsive. The baseline median serum CLDN1 and CLDN7 levels were significantly lower in non-metastatic and metastatic patients compared with those in healthy controls (CLND1, P=0.008 and 0.002; and CLND7, P=0.002 and 0.002, respectively). Moreover, known clinical variables, including poor performance status and high carcinoembryonic antigen (CEA) levels were found to be associated with lower serum CLDN1 concentrations for all patients (P=0.03 and P=0.03, respectively). High T stage and high CEA levels were found to be correlated with lower serum CLDN7 concentrations for all patients (P=0.04 and 0.03, respectively). A correlation was identified between CLDN1 and CLDN7 levels in non-metastatic and metastatic CRC patients (both P values <0.001). Our study results did not reveal any statistical significance for serum CLDN1 or CLND7 concentrations regarding progression-free and overall survival rate. Therefore, reduced serum levels of CLDN1 and CLND7 may be useful markers in the differential diagnosis of CRC. PMID- 26807231 TI - Pertuzumab for the treatment of patients with human epidermal growth factor receptor 2-positive breast cancer in Japan. AB - Pertuzumab, a novel anti-human epidermal growth factor receptor 2 (HER2) agent, is effective for metastatic HER2-positive breast cancer when used in combination with taxane and trastuzumab. The aim of the present study was to describe the use of pertuzumab in Japan. A phase I clinical trial of pertuzumab for HER2-positive metastatic breast cancer was first conducted in the United States in 2001 (study ID no. TOC2297g) and for HER2-positive solid cancers in Japan in 2004 (study ID no. JO17076). However, Japanese patients were not enrolled in a global phase II trial for metastatic breast cancer (study ID no. BO17929) and no phase II trial of pertuzumab for Japanese patients has yet been conducted. A phase III trial on pertuzumab for metastatic breast cancer (CLEOPATRA study), which included 53 Japanese patients, revealed that pertuzumab significantly prolonged progression free and overall survival. However, the superiority of the pertuzumab group was not verified in the subgroup analysis of Japanese patients, which was not a preplanned analysis. Therefore, a postmarketing clinical trial for Japanese patients with HER2-positive metastatic breast cancer (COMACHI study) was initiated in November, 2013, to investigate the clinical effectiveness of pertuzumab in Japanese patients. As of December, 2014, global trials on pertuzumab in the metastatic and adjuvant settings are currently ongoing. These trials included Japanese patients with HER2-positive breast cancer. Pertuzumab was approved in Japan in August, 2013 due to the positive findings of the CLEOPATRA study. Unlike the United States and Europe, the Japanes Pharmaceutical and Medical Devices Agency approved the administration of pertuzumab as second- or later-line treatment for HER2-positive metastatic breast cancer, as well as first-line treatment. Furthermore, pertuzumab may be used in combination with other chemotherapeutic agents, with the exception of docetaxel. The approval of the expanded use of pertuzumab is likely to accelerate the market penetration of pertuzumab in Japan more quickly compared with other countries. PMID- 26807232 TI - Prevalence of K-Ras mutations in hepatocellular carcinoma: A Turkish Oncology Group pilot study. AB - Hepatocellular carcinoma (HCC) is the fifth most common male-predominant type of cancer worldwide. There is no effective treatment regimen available for advanced stage disease and chemotherapy is generally ineffective in these patients. The number of studies on the prevalence of K-Ras mutations in HCC patients is currently limited. A total of 58 patients from 6 comprehensive cancer centers in 4 metropolitan cities of Turkey were enrolled in this study. Each center committed to enroll approximately 10 random patients whose formalin-fixed paraffin-embedded tumor tissues were available for K-Ras, exon 2 genotyping. Two methods were applied based on the availability of adequate amounts of tumor DNA. In the first method, the samples were processed using TheraScreen. The genomic DNA was further used to detect the 7 most frequent somatic mutations (35G>A; 35G>C; 35G>T; 34G>A; 34G>C; 34G>T and 38G>A) in codons 12 and 13 in exon 2 of the K-Ras oncogene by quantitative polymerase chain reaction (PCR). In the second method, the genomic DNA was amplified by PCR using primers specific for K-Ras exon 2 with the GML SeqFinder Sequencing System's KRAS kit. The identified DNA sequence alterations were confirmed by sequencing both DNA strands in two independent experiments with forward and reverse primers. A total of 40 samples had adequate tumor tissue for the mutation analysis. A total of 33 (82.5%) of the investigated samples harbored no mutations in exon 2. All the mutations were identified via a direct sequencing technique, whereas none were identified by TheraScreen. In conclusion, in our patients, HCC exhibited a remarkably low (<20%) K-Ras mutation rate. Patients harboring K-Ras wild-type tumors may be good candidates for treatment with epidermal growth factor inhibitors, such as cetuximab. PMID- 26807233 TI - Endothelial protein C receptor gene 6936A/G single-nucleotide polymorphism as a possible biomarker of thrombotic risk in acute myeloid leukemia. AB - Protein C (PC) is a natural anticoagulant, which interacts with the endothelial PC receptor (EPCR). EPCR single-nucleotide polymorphism (SNP) 6936A/G results in high levels of a free soluble form of EPCR (sEPCR) and may affect the risk of coagulation. The objective of this study was to assess whether the 6936A/G SNP of the EPCR gene is involved in the procoagulant activity displayed by hematological malignancies. EPCR 6936A/G polymorphism analysis was performed in 205 patients with hematological malignancies and in 63 healthy controls. All the subjects were genotyped for the EPCR 6936A/G SNP (AA, AG and GG genotypes). The 6936A/G polymorphism distribution was similar between healthy donors and patients. The association between EPCR 6936A/G SNP and thrombosis was investigated in 110 patients. The disease-wise break-up revealed that 55 of the patients suffered from acute myeloid leukemia (AML). In AML patients, the incidence of thrombosis was 28.3% and significantly higher in the 6936AG compared with that in the 6936AA genotype (50 vs. 22%, respectively). In conclusion, this study revealed a significant association of the 6936AG genotype of EPCR with thrombotic events in AML. Therefore, the presence of the 6936AG genotype in AML patients may be considered as a risk indicator of thrombosis. PMID- 26807234 TI - Clinical implications of human leukocyte antigen class I expression in endometrial cancer. AB - Decreased expression of human leukocyte antigen (HLA) class I molecules, which is found in several types of cancer, is associated with worse clinical prognosis in cancer patients. The present study was undertaken to investigate the association of immunohistochemical HLA class I expression patterns with clinicopathological factors and prognosis in 96 endometrial cancer patients. HLA class I is composed of a heavy chain (HC-10) and a beta2-microglobulin (beta2-m) light chain. The HLA class I expression patterns were classified as positive when both HC-10 and beta2 m were strongly stained and negative in all other cases. The negative staining pattern was associated with advanced International Federation of Gynecology and Obstetrics stage (P<0.001), lymphovascular space involvement (LVSI) (P=0.003) and lymph node metastasis (P=0.005). Moreover, these cases exhibited worse progression-free survival (PFS) and overall survival (OS) rates compared with positive cases (P=0.005 and P=0.014, respectively). However, the multivariate analysis did not identify HLA class I expression as an independent predictive factor for PFS and OS. In conclusion, HLA class I expression may be useful for predicting postoperative outcome in endometrial cancer, as well as well-known predictive prognostic factors, such as lymph node metastasis and LVSI. PMID- 26807235 TI - Amplification of the bromodomain-containing protein 4 gene in ovarian high-grade serous carcinoma is associated with worse prognosis and survival. AB - High-grade serous carcinoma (HGSC) of the ovary is an aggressive and devastating neoplasm and the identification of novel therapeutic targets may result in a significant decrease in patient morbidity and mortality. Over the last few years, chromatin regulators have become attractive targets for cancer therapy. More specifically, bromodomain-containing protein 4 (BRD4), a protein that is associated with acetylated chromatin and transcriptional activation, has been shown to selectively regulate the transcription of key oncogenic drivers, such as CMYC, in several tumor types. The Cancer Genome Atlas (TCGA) Project has molecularly characterized the genome of ovarian serous carcinomas, which enabled us to study the association of genomic alterations of BRD4 with patient survival and clinicopathological characteristics. Our analysis using clinical and genomic data from the TCGA ovarian carcinoma samples revealed that somatic amplification of BRD4 (observed in 12% of the cases) was correlated with increased BRD4 mRNA levels and is significantly associated with worse overall and progression-free survival compared to wild-type cases. These findings support the hypothesis that future studies and trials investigating newly developed BRD4 inhibitors are required in a subset of patients with ovarian HGSC. PMID- 26807236 TI - Angiotensin II type-1 receptor blockers enhance the effects of bevacizumab-based chemotherapy in metastatic colorectal cancer patients. AB - The local renin-angiotensin system promotes angiogenesis and vascular proliferation via expression of vascular endothelial growth factor or epidermal growth factor receptor. We hypothesized that angiotensin II type-1 receptor blockers (ARBs) in combination with bevacizumab (Bev) may improve clinical outcomes in patients with metastatic colorectal cancer (mCRC). A total of 181 patients with histopathologically confirmed mCRC treated with first-line oxaliplatin-based chemotherapy in combination with Bev were enrolled between June, 2007 and September, 2010. The patients were divided into two groups based on the presence or absence of treatment with ARBs prior to the initiation of second-line chemotherapy. Kaplan-Meier analysis and Cox proportional hazard modeling were used in the statistical analysis. The median progression-free survival (PFS) in patients undergoing second-line chemotherapy in combination with Bev and ARBs (n=56) vs. those treated in the absence of ARBs (n=33) was 8.3 vs. 5.7 months, respectively [hazard ratio (HR)=0.57, 95% confidence interval (CI): 0.35-0.94, P=0.028]. The median overall survival (OS) was 26.5 vs. 15.2 months, respectively (HR=0.47, 95% CI: 0.25-0.88, P=0.019). In the multivariate analysis, the use of ARBs was independently associated with prolongation of OS and PFS. In conclusion, the use of ARBs prolonged survival in mCRC patients. PMID- 26807237 TI - Low prevalence of Merkel cell polyomavirus with low viral loads in oral and maxillofacial tumours or tumour-like lesions from immunocompetent patients: Absence of Merkel cell polyomavirus-associated neoplasms. AB - It was recently demonstrated that ~80% of Merkel cell carcinomas (MCCs) harbour a novel polyomavirus, Merkel cell polyomavirus (MCPyV). MCPyV has been detected in various human tissue samples. However, previous studies on the prevalence of MCPyV in oral tumours or tumour-like lesions are incomplete. To address this issue, we measured MCPyV DNA quantity using quantitative polymerase chain reaction (qPCR) in 327 oral tumours or tumour-like lesions and 54 jaw tumours or cyst lesions from 381 immunocompetent patients, as well as in 4 oral lesions from 4 immunosuppressed patients. qPCR revealed a low MCPyV prevalence (25/381, 6.6%) with low viral loads (0.00024-0.026 copies/cell) in oral and maxillofacial tumours and tumour-like lesions from immunocompetent patients. The prevalence was 7/176 (4.0%) in invasive squamous cell carcinomas (SCCs) [2/60 (3.33%) SCCs of the tongue, 4/52 (7.7%) SCCs of the gingiva and 1/19 (5.3%) SCCs of the floor of the mouth], 1/10 (10%) in dysplasias, 1/5 (20%) in adenocarcinomas, 2/13 (15.4%) in adenoid cystic carcinomas, 1/10 (10%) in non-Hodgkin's lymphomas, 3/10 (30%) in lipomas, 3/5 (60%) in neurofibromas, 1/3 (33.3%) in Schwannomas, 2/12 (16.7%) in Warthin's tumours, 2/11 (18.2%) in pyogenic granulomas, 1/14 (7.1%) in radicular cysts and 1/12 (8.3%) in ameloblastomas. The prevalence in lesions from immunosuppressed patients (1/4, 25%) was higher compared with that in lesions from immunocompetent patients (25/381, 6.6%), but the difference was not statistically significant. To the best of our knowledge, this study was the first to report prevalence data of MCPyV in tumours and cysts of the jaws (2/54, 3.7%). These data indicated absence of MCPyV-related tumours or tumour-like lesions in the oral cavity and jaws and suggested that the detected MCPyV DNA was derived from non-neoplastic background tissues with widespread low-level MCPyV infection. PMID- 26807238 TI - Laparoscopic jejunostomy for obstructing upper gastrointestinal malignancies. AB - The aim of this study was to describe a minimally invasive laparoscopic jejunostomy (Lap-J) technique for obstruction due to upper gastrointestinal malignancies and evaluate the nutritional benefit of Lap-J during neoadjuvant chemotherapy (NAC) in cases with obstructing esophageal cancer. Under general anesthesia, the jejunum 20-30 cm distant from the Treitz ligament was pulled out through an extended umbilical laparoscopic incision and a jejunal tube was inserted to 30 cm. The loop of bowel was gently returned to the abdomen and the feeding tube was drawn through the abdominal wall via the left lower incision. The jejunum was then laparoscopically sutured to the anterior abdominal wall. Lap J was performed in 26 cases. The median operative time was 82 min. The postoperative course was uneventful. Lap-J prior to NAC was not associated with a decrease in body weight or serum total protein during NAC, compared with patients who received NAC without Lap-J. This minimally invasive jejunostomy technique may be particularly useful in patients in whom endoscopic therapy is not feasible due to obstruction from upper gastrointestinal malignancies. PMID- 26807239 TI - Computed tomography imaging characteristics of synchronous gastrointestinal stromal tumors in patients with gastric cancer and correlation with clinicopathological findings. AB - This study was conducted to analyze the computed tomography (CT) imaging and clinicopathological characteristics of synchronous gastrointestinal stromal tumors (GISTs) in patients with gastric cancer. We retrospectively reviewed the CT images in 18 cases of immunohistochemically confirmed synchronous GISTs in patients with primary gastric cancer. Relevant histology and clinical data were also obtained. Multi-slice CT (MSCT) identified suspected synchronous GISTs in 26 patients, of which 18 were finally confirmed. Of the 18 patients, 12 were male and 6 female, with a mean age of 69.2 years. All 18 lesions were discovered as a solitary mass, ranging in size from 1.0 to 6.5 cm (mean, 2.2 cm). The lesions were predominantly located in the gastric fundus and were characterized by an ovoid shape, well-defined margins and isodensity, with slight to moderate gradual enhancement on MSCT. There was no evidence of necrosis, hemorrhage or cystic degeneration, irrespective of the tumor size. Synchronous GISTs exhibited spindle cell morphological characteristics and specific immunohistochemical properties, and were classified as being of low or very low malignant potential. In conclusion, since gastric cancer patients with a synchronous GIST are rare, a solitary, ovoid and well-defined mass with slight to moderate gradual enhancement following contrast agent injection may be suggestive of this diagnosis, although detection of synchronous GISTs does not appear to significantly affect therapy and outcome. PMID- 26807240 TI - Combined assays for serum carcinoembryonic antigen and microRNA-17-3p offer improved diagnostic potential for stage I/II colon cancer. AB - Colorectal cancer is among the leading causes of cancer-related mortality, one of the main reasons for which is the lack of an effective screening method for early stage disease. The levels of carcinoembryonic antigen (CEA) and microRNA (miR)-17 3p in the serum of 70 patients with stage I/II colon cancer and 70 healthy volunteers were determined, and the diagnostic value of CEA plus miR-17-3p detection for colon cancer was assessed. The levels of CEA were measured by a radioimmunoassay method, and those of miR-17-3p using the reverse transcription quantitative polymerase chain reaction method. miR-16 was used as the endogenous control, as it displayed high stability, high abundance and low variability in the analyzed serum samples. The receiver operating characteristic (ROC) curve analysis indicated the potential diagnostic value of the two markers and the area under the ROC curve (AUC) for CEA and miR-17-3p was 0.719 (95% CI: 0.658-0.843) and 0.807 (95% CI: 0.748-0.906), respectively. At a threshold of 9.6 ng/ml for CEA, the optimal sensitivity and specificity were 74.6 and 84.3%, respectively, in discriminating colon cancer patients from healthy controls. At a threshold of 2.98 for miR-17-3p, the sensitivity and the specificity were 83.6 and 72.9%, respectively. A combined ROC analysis using CEA and miR-17-3p revealed an AUC of 0.929 (95% CI: 0.834-0.978) with a sensitivity of 96.4% and a specificity of 95.7% in discriminating colon cancer patients from healthy controls. In conclusion, both CEA and miR-17-3p were highly expressed in the serum of our series of colon cancer patients. CEA plus miR-17-3p detection significantly increased the sensitivity and specificity in discriminating stage I/II colon cancer patients from healthy controls. Therefore, combined detection of serum CEA and miR-17-3p levels may have the potential to become a new laboratory method for the early clinical diagnosis of colon cancer. PMID- 26807241 TI - Extramedullary blast crisis as initial presentation in chronic myeloid leukemia with the e1a2 BCR-ABL1 transcript: A case report. AB - A 23-year-old woman presented with enlarged right inguinal lymph nodes. The pathological examination of the nodes revealed infiltration by myeloid sarcoma. A bone marrow smear and biopsy revealed cytogenetic abnormalities, with 46,XX,t(9;22) and chronic myeloid leukemia (CML) was diagnosed. The e1a2 BCR-ABL1 fusion transcript was detected. The patient received imatinib-based combined chemotherapy, allogeneic hematopoietic stem cell transplantation, donor lymphocyte infusions and dasatinib treatment. The patient achieved complete response and has remained leukemia-free for >48 months. To the best of our knowledge, this is the first case report of CML with the e1a2 BCR-ABL1 transcript, with extramedullary blast crisis as the initial presentation. The aim of the present study was to discuss this special case with reference to the literature. PMID- 26807242 TI - Clinical characteristics and prognostic analysis of Krukenberg tumor. AB - Krukenberg tumor is a rare metastastic tumor of the ovary, characterized by poor prognosis. In order to analyze the clinical characteristics and prognostic factors, we retrospectively investigated 128 patients who were diagnosed with Krukenberg tumor between January, 1990 and December, 2010. The median patient age was 48 years. The median overall survival (OS) of Krukenberg tumor for all patients was 16 months (95% CI: 15-19 months). The median OS among patients with Krukenberg tumors of gastric, colorectal, breast and other origins (including appendix, gallbladder, small intestine and unknown primary) was 11, 21.5, 31 and 19.5 months, respectively (P<0.0001). In the univariate analysis, synchronous metastasis, no chemotherapy, ovarian metastasis beyond the pelvis, ascites and no metastasectomy were identified as significant poor prognostic factors. The multivariate analysis suggested that synchronous metastasis (P=0.0080), pelvic invasion (P=0.0138), ascites (P<0.0001) and no metastasectomy (P=0.0060) were independent factors for predicting unfavorable OS. It was suggested that the prognosis of Krukenberg tumor is dismal and ovarian metastasectomy may prove beneficial. Adequate treatment planning is required for this group of patients. PMID- 26807243 TI - Promoter mutation of tumor suppressor microRNA-7 is associated with poor prognosis of lung cancer. AB - The significance of promoter mutations of microRNAs (miRNAs) in lung cancer is poorly understood. Recent evidence demonstrated that miRNA-7 (miR-7), a unique member of the miRNA family, exhibited decreased expression and has emerged as an important regulator in lung tumorigenesis. However, the mechanism underlying the downregulation of miR-7 in lung cancer remains largely unknown. In this study, we investigated the sites of mutation of the miR-7 promoter in lung cancer tissues using DNA sequencing. We identified a G->C change at the -617 site (25/39, 64.1%) and an A->G change at the -604 site (20/39, 51.3%) in the miR-7 promoter region in lung cancer tissues. Moreover, the expression of miR-7 in cancer tissue with promoter site mutations was lower compared with that in cancer tissue without mutations (P<0.05). Furthermore, we demonstrated that mutations at these sites may decrease the activity of the miR-7 promoter and alter the expression of miR 7. Notably, mutations at these sites of the miR-7 promoter were found to be closely associated with poor prognosis of lung cancer patients (P=0.037). These data may provide novel insight on the altered expression of specific miRNA molecules in lung cancer and ultimately prove to be helpful in the development of prognostic and therapeutic strategies against lung cancer. PMID- 26807244 TI - Clinicopathological characteristics of infiltrating lobular breast carcinoma in elderly women: Preliminary results. AB - This study was conducted to investigate the clinicopathological parameters in elderly women (aged >70 years) with infiltrating lobular carcinoma (ILC) of the breast and compare the results with those obtained from younger patients (aged 55 70 years). The study sample included a total of 46 women with ILCs, 10 aged >70 and 36 aged 55-70 years. The parameters analysed were tumor size, histological grade (HG), axillary lymph node involvement, distant metastasis and immunohistochemical expression of estrogen, progesterone and androgen receptors, Ki67, p53 and B cell lymphoma 2. Compared to women aged 55-70 years, ILCs in women aged >70 years were commonly of larger size (P=0.068) and were more frequently HG3 (P=0.024). There were no statistically significant differences in the other parameters analysed. Furthermore, we were unable to determine differences in cancer recurrence and mortality in the two patient subgroups during our follow-up. In conclusion, our preliminary results, based on the limited number of cases included in this study, indicate that i) ILCs in women aged >70 years tended to be larger compared to those in women aged 55-70 years and were more frequently of grade 3; and ii) there were no significant differences in terms of recurrence and mortality between the two patient subgroups during our follow-up. PMID- 26807245 TI - Detection of early renal injury in children with solid tumors undergoing chemotherapy by urinary neutrophil gelatinase-associated lipocalin. AB - Acute kidney injury (AKI) is a complication in children with solid tumors undergoing chemotherapy, as it may prevent the use of therapy protocols and also hinder the supportive and diagnostic procedures. Thus, there is an urgent requirement for early predictive biomarkers of AKI. The most promising novel AKI biomarker is neutrophil gelatinase-associated lipocalin (NGAL). The aim of the present study was to compare the predictability of NGAL as a biomarker of AKI with creatinine as a traditional biomarker in children with solid tumors under chemotherapy. The study was performed on 30 patients with different types of solid tumors (reuroblastoma, Wilms tumor, medulloblastoma, rhabdomyosarcoma and Ewing sarcoma) and 20 control subjects. Urinary NGAL (uNGAL) and serum creatinine samples were taken three times: Baseline before the beginning of the treatment, one week after chemotherapy and at the end of the chemotherapy protocol. AKI is defined as a change in creatinine level by >50% of the baseline. The creatinine level only rises to this level in the third sample, while uNGAL increases significantly in the second and third samples with percentage of change 376.8 and 698.2%, respectively, which is highly significant (P<0.001). When comparing the predictive value of serum creatinine for AKI depending on the receiver operating characteristic curve with that of uNGAL, the area under the curve (AUC) for creatinine was 0.60 with a standard error (SE) of 0.086 and 95% confidence interval (CI) between 0.432 and 0.768, while that of uNGAL was highly predictive with an AUC of 0.847, SE 0.55 and 95% CI between 0.739 and 0.955. Depending only on the creatinine level for detecting the AKI will markedly delay the diagnosis; however, uNGAL is detected earlier, and is easier and more reliable as a marker for AKI in children with solid tumors undergoing chemotherapy. PMID- 26807246 TI - Flap endonuclease 1 polymorphisms (rs174538 and rs4246215) contribute to an increased cancer risk: Evidence from a meta-analysis. AB - Flap endonuclease-1 (FEN1) is a key factor during the maintenance of genomic stability and protection against tumorigenesis. Since the identification of functional polymorphisms of FEN1 (rs174538 and rs4246215), numerous studies have evaluated the association between the two single-nucleotide polymorphisms and cancer risk. To derive a more precise estimation, a meta-analysis was performed on the association between the FEN1 polymorphisms (rs174538 and rs4246215) and cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of the associations. Thirteen case-control studies, including 5,108 cases and 6,382 case-free controls, were identified. For rs174538, individuals with the GG or GA genotype had an increased risk of cancer when compared to the -69AA genotype (AA vs. GG: OR, 1.85; 95% CI, 1.65-2.08; P<0.00001; AA vs. GA: OR, 1.43; 95% CI, 1.27-1.60; P<0.00001; AA vs. GG+GA: OR, 1.28; 95% CI, 1.16-1.42; P<0.00001). For rs4246215, similar results were identified, as the GG or GT genotype was significantly associated with the increased cancer risk when compared to TT (TT vs. GG: OR, 1.71; 95% CI, 1.52 1.92; P<0.00001; TT vs. GT: OR, 1.34; 95% CI, 1.20-1.50; P<0.00001; TT vs. GG+GT: OR, 1.50; 95% CI, 1.35-1.67; P<0.00001). The present meta-analysis indicated that FEN1 rs174538 and rs4246215 polymorphisms may contribute to an increased risk of cancer. PMID- 26807247 TI - Promoter methylation of BRCA1 is associated with estrogen, progesterone and human epidermal growth factor receptor-negative tumors and the prognosis of breast cancer: A meta-analysis. AB - Aberrant methylation of the breast cancer susceptibility gene 1 (BRCA1) promoter is a mechanism for its functional inactivation. It may potentially be used as a prognostic marker in studies for patients with breast cancer and plays an important role in tumorigenesis. Numerous studies have suggested that the methylation of the BRCA1 promoter is associated with the prognosis of breast cancer. However, the prognosis of BRCA1 promoter methylation in breast cancer patients of different ethnicities remains ambiguous. The present meta-analysis was performed to adjust and augment a previously published study, which estimated the correlations between promoter methylation of BRCA1 and the clinical outcomes of breast cancer patients. These results indicated that BRCA1 methylation was significantly correlated with a poor prognosis of breast cancer, particularly for Asian patients, but the correlation was over-estimated in the previous study. The combined hazard ratios (HRs) in the present study were 1.76 (1.15-2.68) and 1.97 (1.12-3.44) for univariate and multivariate analysis of overall survival, which were different from 2.02 (1.35-3.03) and 1.38 (1.04-1.84) in the previous study. For studies of disease-free survival, the univariate and multivariate analyses also have different pooled HRs: 2.89 (1.73-4.83) and 3.92 (1.49-10.32) in the previously published study and 1.28 (0.68-2.43) and 1.64 (0.64-4.19) in the present study. In addition, the BRCA1 promoter regions used to detect the hypermethylation were different. All the studies using the Baldwin's primer reported that breast cancer patients with BRCA1 promoter methylation had a better prognosis. There were also correlations between BRCA1 promoter methylation and receptor-negativity of the estrogen receptors, progesterone receptor, human epidermal growth factor receptor 2 and a triple-negative status. Patients with the estrogen, progesterone and epidermal growth factor-related receptor-negative status were more likely to be negative for the BRCA1 protein. PMID- 26807248 TI - Evaluation of prognostic scoring systems for bone metastases using single-center data. AB - Recent progress in cancer treatment has improved patient survival, but has increased the number of patients with metastatic bone tumors. Data were collected from all bone metastasis patients at Kagoshima University, where almost all patients with metastatic bone tumors who reside in Kagoshima province are treated surgically. The scoring systems used in bone metastasis patients were then evaluated to identify those most suitable for our patients. Clinical data were collected from 145 patients with bone metastases. The patients were assigned prognostic scores based on four scoring systems, namely those described by the Ratasvuori, Mizumoto, Tokuhashi and Katagiri groups. Statistical examinations were performed to assess patient distribution regarding prognostic factors and the four data sets reported in the literature. The patient distributions for all prognostic factors were significantly different between the Scandinavian Sarcoma Group (SSG) and Kagoshima data. The distributions of patients for 3 of 5 and for 5 of 7 prognostic factors were statistically different between the Kagoshima data and the Katagiri and Tokuhashi data, respectively. Additionally, the distribution of patients in each scoring group was statistically different between the Kagoshima data and the Katagiri, Tokuhashi and Mizumoto data. The predictions of prognosis were significantly different between the results of each group and ours. The Tokuhashi scoring system detected the highest survival at 6 months (88.8%) in the Kagoshima data. Patients with a life expectancy of >6 months benefited from tumor excision and reconstruction. These findings suggest that the Tokuhashi scoring system is the most suitable for identifying patients who should be assessed for curative surgical intervention. SSG scoring, however, was suitable for identifying patients expected to survive for <6 months (91.3%). Prior to selecting a scoring system to predict prognosis, it is important to determine which scoring system is the most appropriate, based on each hospital's particular characteristics. PMID- 26807249 TI - Patterns of epidermal growth factor receptor mutation in non-small-cell lung cancers in the Gulf region. AB - The aim of the present study was to determine the prevalence of epidermal growth factor receptor mutations (EGFRmut) in the Gulf region (GR) and its correlation with demographic and clinical characteristics. A multisite retrospective study was conducted, including institutions from Saudi Arabia, the United Arab Emirates and Qatar. All consecutive patients with non-small-cell lung cancer tested for EGFRmut were eligible. Data collected included demographic information, disease characteristics and EGFR test results. Data on 230 patients were obtained. The median age of the patients was 61 years (range, 26-87 years); 169 patients (69.83%) were male and 204 (88.7%) were Arab. The histological subtype was adenocarcinoma in 191 (83.4%) and squamous cell carcinoma in 21 cases (9.17%). Overall, EGFRmut were detected in 66 patients (28.7%), with a prevalence of 32.46% in adenocarcinoma. No squamous cell carcinomas were found to harbor EGFRmut. The univariate and multivariate analyses revealed that female gender, non-smoking status and adenocarcinoma subtype were significant predictors for EGFRmut. There was no difference between Arabs and non-Arabs. In conclusion, to the best of our knowledge, this is the first multisite study to report the prevalence of EGFRmut in the GR population, which was found to be higher compared with that in Western, but lower compared with that in Far Eastern populations. Studies evaluating the efficacy of targeted therapy in this population are underway. PMID- 26807250 TI - A phase I multicenter study of antroquinonol in patients with metastatic non small-cell lung cancer who have received at least two prior systemic treatment regimens, including one platinum-based chemotherapy regimen. AB - Antroquinonol is isolated from Antrodia camphorata, a camphor tree mushroom, and is a valuable traditional Chinese herbal medicine that exhibits pharmacological activities against several diseases, including cancer. This first-in-human phase I study of antroquinonol included patients with metastatic non-small-cell lung cancer who had received at least two prior systemic treatment regimens. An open label, dose escalation, pharmacokinetic (PK) study was conducted to determine the maximum tolerable dose (MTD), dose-limiting toxicities (DLTs), and safety/tolerability and preliminary efficacy profiles of antroquinonol. The patients received escalating doses of once-daily antroquinonol in 4-week cycles (up to 3 cycles). The escalated doses were 50-600 mg. PKs were evaluated on day 1 and 28 of cycle 1. Between January, 2011 and October, 2012, 13 patients with metastatic adenocarcinoma were enrolled. No DLTs occurred in any patient at any dose level. Tmax was observed between 1.00 and 3.70 h under single-dose conditions, and at 1.92-4.05 h under multiple-dose conditions. The mean elimination half-life ranged between 1.30 and 4.33 h, independent of the treatment dose. Antroquinonol at all dose levels had a mild toxicity profile, with no reported treatment-related mortality. The most common treatment-related adverse events were diarrhea, vomiting and nausea. The best tumor response was stable disease in 3 patients. In conclusion, antroquinonol at all dose levels, administered daily for 4 weeks, was generally safe and well tolerated, without DLTs. The recommended dose level for a phase II study is >=600 mg daily. PMID- 26807251 TI - Role of ventriculoperitoneal shunting in patients with neoplasms of the central nervous system: An analysis of 59 cases. AB - Approximately 1-5% of patients with cerebral metastasis and ~40% of patients with primary brain tumors suffer from hydrocephalus. These patients often exhibit a poor prognosis. The aim of the present study was to reassess the validity of ventriculoperitoneal shunting (VPS) with the assistance of the general surgeon in oncological patients. A total of 59 patients underwent first-time VPS at the Beth Israel Deaconess Medical Center (Boston, USA) between 2004 and 2012; 40 patients had hydrocephalus from brain metastasis and 19 from primary tumors. The analyzed independent variables included demographics, body mass index, past medical history, clinical presentation, indication for surgery, Karnofsky performance status (KPS) score and surgical technique; the dependent variables were postoperative symptoms and occurrence, cause and time of shunt failure. The outcomes were analyzed with the t-test and Kaplan-Meier estimates for shunt survival. The mean age of the patients was 57.2 years and the mean operative time was 50.4 min. Symptomatic palliation was achieved in 93% of the cases; patients with severe symptoms, such as debilitating headaches, nausea and vomiting, benefited significantly from VPS. The mean follow-up time was 6.3 months; complications occurred in only 7 patients (11.8%) during follow-up: 2 in the proximal shunt (1 infection and 1 obstruction), both requiring revision, 1 infection in the distal catheter requiring shunt removal, 2 cases of intracerebral bleeding that were monitored with computed tomography scans, 1 wound infection treated with antibiotics and 1 valve complication that required temporary revision. The initial and 3-month KPS scores were 65+/-16.4 and 75+/ 16.0, respectively. The mean overall shunt survival was 6.4 months (range, 1.0 day-76.0 months) from the placement of the VP shunt. At 3 months after VPS, 93.5% of the patients remained alive with functioning shunts and at 1 year 87% of the shunts were still functioning. In conclusion, VPS remains a valid option for cancer patients with low KPS, as it improves the quality of life in such patients, even in the setting of previous infection, hemorrhage, or leptomeningeal disease, since shunt patency outlasts the overall survival of nearly all patients. PMID- 26807252 TI - Chemotherapy for urothelial carcinoma in renal transplantation patients: Initial results from a single center. AB - The aim of this study was to assess the safety and efficacy of gemcitabine plus cisplatin/carboplatin (GC/GCa) chemotherapy in renal transplantation (RT) patients with urothelial carcinoma (UC). We reviewed the records of 12 RT patients with metastatic or locally advanced UC who received chemotherapy at our institution since January, 2013. All the patients received intravenous gemcitabine (800 mg/m2) on days 1, 8 and 15, plus cisplatin (70 mg/m2) or carboplatin (area under the curve = 5) on day 2, every 28 days. A total of 10 patients completed all the cycles, while 1 patient discontinued treatment due to disease progression and 1 patient discontinued due to non-medical reasons. In total, 12 patients received a median of four cycles of chemotherapy. The overall response rate was 50% (4/8 cases) in patients with measurable lesions. At the time of the study, 5 patients had succumbed to the disease (overall survival, 9.2 months), while 7 patients remained alive (follow-up time, 13.3 months). The most common toxicities were myelosuppression and gastrointestinal effects. Therefore, the GC/GCa regimen was found to be effective and tolerable in RT patients with UC. However, further studies involving more patients and control groups are required to confirm our results. PMID- 26807253 TI - Neuroendocrine differentiation in castration-resistant prostate cancer: A case report. AB - The most common type of prostate cancer is acinar adenocarcinoma, which is androgen-dependent and, therefore, treated with chemical or surgical castration and androgen receptor inhibition. However, the disease usually progresses to castration-resistant prostate cancer (CRPC). A neuroendocrine pattern is frequently observed in the cellular composition of CRPC, which is considered to emerge as an effect of androgen deprivation therapy. This is the case report of a 69-year-old patient with prostate adenocarcinoma, who, after an initial period of disease control with radiotherapy and antiandrogens, was diagnosed with CRPC with high levels of prostate-specific antigen (PSA), unresponsive to androgen inhibition, with accompanying lung and osseous metastases. Bronchial biopsy of the lung metastasis revealed infiltration by non-small-cell adenocarcinoma of prostatic origin with neuroendocrine characteristics. On somatostatin receptor scintigraphy with 99mTc-octreotide, there was high uptake by almost all known lung and osseous metastases. The patient was subsequently treated with a combination of docetaxel and octreotide, and a partial response was observed 6 months later, with reduction of the PSA level and the size of the lung metastasis. The aim of the present study was to provide a clinical example of the previously demonstrated, in vitro and in vivo, synergistic antitumor activities of docetaxel and octreotide in cases of CRPC selected by means of histological confirmation of their neuroendocrine nature and somatostatin receptor scintigraphy. PMID- 26807254 TI - Benign pelvic masses masquerading as adnexal cancer during pregnancy on ultrasound: A retrospective study of 5 years. AB - This study was conducted to investigate the sonographic characteristics of benign adnexal masses misdiagnosed as malignancy, and determine whether sonographic findings may help distinguish these lesions from malignant tumors during pregnancy at a single center. We herein present our experience with pregnant women with benign adnexal masses misdiagnosed as malignancy by ultrasound and operated on during pregnancy or after delivery. A total of 4 cases of benign pelvic masses were misdiagnosed as adnexal cancer over a 5-year period, including an ovarian theca cell tumor with luteinization, an obsolete ectopic pregnancy of fallopian tube, an ovarian mature teratoma with abundant nervous tissue and a uterine myoma with degeneration. The masses were characterized by abundant blood flow and heterogeneous echo on ultrasound. In conclusion, adnexal masses identified during pregnancy exhibiting abundant blood flow and heterogeneous echo may not represent malignancy, even in the presence of increased carbohydrate antigen 125 levels. In certain cases, benign adnexal masses may be initially misdiagnosed as malignant during pregnancy. PMID- 26807255 TI - Severe ileitis associated with capecitabine: Two case reports and review of the literature. AB - Capecitabine is a commonly used anticancer drug, which has been associated with adverse events, including skin and gastrointestinal symptoms, such as vomiting and diarrhea. We herein present treated two rare cases of capecitabine-associated ileitis. In one of the patients, ileitis occurred during combination chemotherapy for metastatic colon cancer, despite previous good tolerance to this drug; the other patient developed ileitis following adjuvant single-agent treatment. The first case is unlike previously reported cases, in which patients had no past exposure to capecitabine. Ileitis may be severe but reversible with early diagnosis and proper supportive treatment, and patients may resume chemotherapy following capecitabine discontinuation. PMID- 26807256 TI - Association of Wilms' tumor 1 gene single-nucleotide polymorphism rs16754 with colorectal cancer. AB - Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Our recent study demonstrated that the expression of Wilms' tumor 1 gene (WT1) is associated with surgical outcome in CRC patients. The present study aimed to investigate the genetic association of the single-nucleotide polymorphism rs16754 in the WT1 gene with the occurrence of CRC, using an age matched case-control study design. In addition, the correlation between genotype and WT1 expression was investigated. Genomic DNA samples from 104 CRC cases, aged 15-65 years, and 208 healthy controls, were genotyped for rs16754 using the TaqMan genotyping method. The genotype distribution conformed to the Hardy Weinberg equilibrium (P=0.80). The overall minor allele frequency (MAF) of rs16754 (allele A) was 0.33. The MAF among CRC cases was significantly higher compared with that in controls (0.39 vs. 0.31, respectively; P=0.03). The AA genotype was significantly associated with the disease (odds ratio = 2.51, 95% confidence interval: 1.24-5.07, P=0.01). Cases with the AA genotype exhibited a significantly poorer 3-year overall survival (60%), compared with those with the GG or GA genotypes (80%) (log-rank test, P<0.01). Reverse transcription quantitative polymerase chain reaction analysis demonstrated that the expression of WT1 in tumor tissues was higher compared with that in normal tissue; however, there were no significant differences in its expression among different genotypes. Therefore, rs16754 was found to be associated with the occurrence and prognosis of CRC in our subjects. PMID- 26807258 TI - Foraging ecology of three sympatric ungulate species - Behavioural and resource maps indicate differences between chamois, ibex and red deer. AB - BACKGROUND: The spatial distribution of forage resources is a major driver of animal movement patterns. Understanding where animals forage is important for the conservation of multi-species communities, since interspecific competition can emerge if different species use the same depletable resources. However, determining forage resources in a spatially continuous fashion in alpine grasslands at high spatial resolution was challenging up to now, because terrain heterogeneity causes vegetation characteristics to vary at small spatial scales, and methods for detection of behavioural phases in animal movement patterns were not widely available. We delineated areas coupled to the foraging behaviour of three sympatric ungulate species (chamois, ibex, red deer) using Time Local Convex Hull (T-LoCoH), a non-parametric utilisation distribution method incorporating spatial and temporal autocorrelation structure of GPS data. We used resource maps of plant biomass and plant nitrogen content derived from high resolution airborne imaging spectroscopy data, and multinomial logistic regression to compare the foraging areas of the three ungulate species. RESULTS: We found significant differences in plant biomass and plant nitrogen content between the core foraging areas of chamois, ibex and red deer. Core foraging areas of chamois were characterised by low plant biomass and low to medium plant nitrogen content. Core foraging areas of ibex were, in contrast, characterised by high plant nitrogen content, but varied in plant biomass, and core foraging areas of red deer had high plant biomass, but varied in plant nitrogen content. CONCLUSIONS: Previous studies carried out in the same study area found no difference in forage consumed by chamois, ibex and red deer. Methodologically, those studies were based on micro-histological analysis of plant fragments identifying them to plant family or functional type level. However, vegetation properties such as productivity (biomass) or plant nutrient content can vary within vegetation communities, especially in highly heterogeneous landscapes. Thus, the combination of high spatial resolution resource maps with a utilisation distribution method allowing to generate behavioural maps (T-LoCoH) provides new insights into the foraging ecology of the three sympatric species, important for their conservation and to monitor expected future changes. PMID- 26807257 TI - Focused ultrasound-aided immunomodulation in glioblastoma multiforme: a therapeutic concept. AB - Patients with glioblastoma multiforme (GBM) exhibit a deficient anti-tumor immune response. Both arms of the immune system were shown to be hampered in GBM, namely the local cellular immunity mediated by the Th1 subset of helper T cells and the systemic humoral immunity mediated by the Th2 subset of helper T cells. Immunotherapy is rapidly becoming one of the pillars of anti-cancer therapy. GBM has not received similar clinical successes as of yet, which may be attributed to its relative inaccessibility (the blood-brain barrier (BBB)), its poor immunogenicity, few characterized cancer antigens, or any of the many other immune mechanisms known to be hampered. Focused ultrasound (FUS) is emerging as a promising treatment approach. The effects of FUS on the tissue are not merely thermal. Mounting evidence suggests that in addition to thermal ablation, FUS induces mechanical acoustic cavitation and immunomodulation plays a key role in boosting the host anti-tumor immune responses. We separately discuss the different pertinent immunosuppressive mechanisms harnessed by GBM and the immunomodulatory effects of FUS. The effect of FUS and microbubbles in disrupting the BBB and introducing antigens and drugs to the tumor milieu is discussed. The FUS-induced pro-inflammatory cytokines secretion and stress response, the FUS induced change in the intra-tumoral immune-cells populations, the FUS-induced augmentation of dendritic cells activity, and the FUS-induced increased cytotoxic cells potency are all discussed. We next attempt at offering a conceptual synopsis of the synergistic treatment of GBM utilizing FUS and immunotherapy. In conclusion, it is increasingly apparent that no single treatment modality will triumph on GBM. The reviewed FUS-induced immunomodulation effects can be harnessed to current and developing immunotherapy approaches. Together, these may overcome GBM-induced immune-evasion and generate a clinically relevant anti-tumor immune response. PMID- 26807259 TI - Comparative dissolution of electrospun Al2O3 nanofibres in artificial human lung fluids. AB - Sub-micron sized alumina fibres were fabricated by electrospinning and calcination of a polymer template fibre. In the calcination step, different controlled temperature heating cycles were conducted to obtain fibres of different crystalline structures. Their biodurabilities were tested at pH 7.4 with lung airway epithelial lining fluid or serum ultrafiltrate (SUF) and at pH 4.5 with macrophage phagolysosomal simulant fluid (PSF). Potential to generate free radicals was tested in vitro. Through the variation in the soak temperature from 650 degrees C to 950 degrees C (experiments S650-S950), the heating protocol affected the morphological characteristics, crystal structure, surface area, and density of the alumina fibres while their dissolution half-times were not significantly affected in SUF or PSF. Fibre samples formed at different heating ramp rates (experiments R93-R600) showed significant variation in the dissolution rates with the highest ramp rate corresponding to the highest dissolution rate. Thus, by increasing the calcination temperature ramp rate the alumina fibres may be produced that have reduced biodurability and lower inflammogenic potential. The fibres with the highest dissolution rated had the least aluminium content. The solubility half-times of the alumina fibres were shortest for fibres calcined at the fastest temperature ramp rate (though soak temperature did not have an effect). The ramp rates also affected the aluminium content of the fibres suggesting that the content may affect the structural strength of the fibres and control the dissolution. PMID- 26807260 TI - Adrenaline aggravates lung injury caused by liver ischemia-reperfusion and high tidal-volume ventilation in rats. AB - BACKGROUND: We often administer adrenaline to improve hypotension of patients undergoing systemic inflammation that is not treated with volume resuscitation. The effects of adrenaline on injured lungs during shock status have not been elucidated. We previously demonstrated that hepatic ischemia-reperfusion followed by high-tidal-volume ventilation-induced systemic inflammation, hypotension, and lung injury in rats. Using this animal model, we investigated the effects of adrenaline on lung injury and hemodynamics. METHODS: Anesthetized rats were ventilated and underwent hepatic inflow interruption for 15 min twice. After the second liver ischemia-reperfusion, the tidal volume was increased to 24 ml . kg( 1) body weight from 6 ml . kg(-1), and 12 rats in each group were observed for 360 min after reperfusion with or without continuous intravenous adrenaline administration. Extra fluid was administered according to the decline in the arterial blood pressure. RESULTS: Adrenaline administration significantly reduced the volume of intravenous resuscitation fluid. The wet-to-dry weight ratio of the lungs was higher (7.53 +/- 0.37 vs. 4.63 +/- 0.35, P < 0.001), the partial oxygen pressure in arterial blood was lower (213 +/- 48 vs. 411 +/- 33, P = 0.004), and the tumor necrosis factor-alpha concentration in bronchoalveolar lavage (BAL) fluid was higher (10(2.64) +/- 10(0.22) vs. 10(1.91) +/- 10(0.27), P = 0.015), with adrenaline. Histopathological examinations revealed marked exudation in the alveolar spaces in rats receiving adrenaline. CONCLUSIONS: Continuous administration of adrenaline partially prevented a rapid decline in blood pressure but deteriorated lung injury in a rat model of liver ischemia reperfusion with high-tidal-volume ventilation. A possibility that adrenaline administration aggravate ventilator-induced lung injury during systemic inflammation should be considered. PMID- 26807261 TI - Risk factors and clinical outcomes of arrhythmias in the medical intensive care unit. AB - BACKGROUND: The clinical impact of arrhythmias on the continuum of critical illness is unclear, and data in medical intensive care units (ICU) is lacking. In this study, we distinguish between different types of arrhythmias and evaluate if their distinction is of clinical importance based on ICU length of stay and mortality outcomes. METHODS: We performed a retrospective analysis of 215 patients in a community-based teaching hospital medical ICU. Variables gathered include sociodemographic data, arrhythmias identified and interpreted by the study team, and admission diagnoses coded into clinical mediator categories based on theorized common risk pathways. Univariable and multivariable Poisson regression models were used to identify risk factors for developing arrhythmias by type, prolonged length of stay, and hospital mortality. RESULTS: Significant arrhythmia was detected in 28.8 % of subjects with most new arrhythmia events developing within the first 3 days of ICU stay. Acute myocardial ischemia and acute kidney injury at the time of ICU admission were associated with an increased risk of developing supraventricular arrhythmias (SVA) (RR = 2.02; 95 % CI 1.08-3.78 and RR = 1.93; 95 %CI 1.09-3.37, respectively). SVA in the first 3 days of ICU stay was associated with an increased risk of prolonged ICU stay (RR = 1.47; 95 % CI 1.09-1.97). After controlling for clinical mediators, development of SVA was not independently associated with in-hospital mortality. No mediators significantly increased the risk of developing ventricular arrhythmias (VA). VA were not associated to prolonged ICU stay but were associated with increased risk of hospital mortality (RR = 1.93; 95 % CI 1.18-3.15). CONCLUSIONS: It is important to distinguish between supraventricular and ventricular arrhythmias for outcomes in the medical ICU setting. Developing a new VA increases the risk of in hospital mortality independently. Developing a new SVA increases the risk of having a prolonged ICU stay but does not appear to increase in-hospital mortality independently. These findings suggest that the development of a VA should be considered an independent morbid event and not necessarily the end result of a complicated clinical course, while a new SVA may be considered a cardiac complication of the disease continuum which may add complexity to an ICU stay. PMID- 26807262 TI - Pseudohypoaldosteronism type 1 due to novel variants of SCNN1B gene. AB - Autosomal recessive pseudohypoaldosteronism type 1 (PHA1) is a rare disorder characterized by sodium wasting, failure to thrive, hyperkalemia, hypovolemia and metabolic acidosis. It is due to mutations in the amiloride-sensitive epithelial sodium channel (ENaC) and is characterized by diminished response to aldosterone. Patients may present with life-threatening hyperkalemia, which must be recognized and appropriately treated. A 32-year-old female was referred to the National Institutes of Health (NIH) for evaluation of hyperkalemia and muscle pain. Her condition started in the second week of life, when she was brought to an outside hospital lethargic and unresponsive. At that time, she was hypovolemic, hyperkalemic and acidotic, and was eventually treated with sodium bicarbonate and potassium chelation. At the time of the presentation to the NIH, her laboratory evaluation revealed serum potassium 5.1 mmol/l (reference range: 3.4-5.1 mmol/l), aldosterone 2800 ng/dl (reference range: <=21 ng/dl) and plasma renin activity 90 ng/ml/h (reference range: 0.6-4.3 ng/ml per h). Diagnosis of PHA1 was suspected. Sequencing of the SCNN1B gene, which codes for ENaC, revealed that the patient is a compound heterozygote for two novel variants (c.1288delC and c.1466+1 G>A), confirming the suspected diagnosis of PHA1. In conclusion, we report a patient with novel variants of the SCNN1B gene causing PHA1 with persistent, symptomatic hyperkalemia. LEARNING POINTS: PHA1 is a rare genetic condition, causing functional abnormalities of the amiloride-sensitive ENaC.PHA1 was caused by previously unreported SCNN1B gene mutations (c.1288delC and c.1466+1 G>A).Early recognition of this condition and adherence to symptomatic therapy is important, as the electrolyte abnormalities found may lead to severe dehydration, cardiac arrhythmias and even death.High doses of sodium polystyrene sulfonate, sodium chloride and sodium bicarbonate are required for symptomatic treatment. PMID- 26807263 TI - Successful fertility treatment with gonadotrophin therapy for male hypogonadotrophic hypogonadism. AB - Gonadotrophin therapy with human chorionic gonadotrophin and recombinant FSH is indicated for use in men with reduced spermatogenesis due to hypogonadotrophic hypogonadism (HH). Patients require regular monitoring for side effects and desired response to treatment. We present a man with HH, azoospermia and a history of previous anabolic steroid usage who had undergone gonadotrophin therapy, had subsequently achieved conception and has now fathered a child. LEARNING POINTS: In total, 15% of couples do not achieve pregnancy within 1 year and seek medical treatment for infertility: male factors contribute to 50% of these.The evaluation of male infertility should include a full history and examination, an endocrine profile and a quality-controlled semen analysis.HH with defective spermatogenesis is an important cause of male infertility in a small percentage of cases.Gonadotrophin therapy requires regular monitoring for side effects and desired response to treatment.Any sustained rise in prostate specific antigen levels should prompt urological assessment for possible prostate biopsy.A multidisciplinary approach is required for gonadotrophin therapy, especially if assisted fertilisation techniques are required once, spermatogenesis is achieved. PMID- 26807264 TI - Response surface modeling of lead (??) removal by graphene oxide-Fe3O4 nanocomposite using central composite design. AB - BACKGROUND: Magnetic graphene oxide (Fe3O4@SiO2-GO) nanocomposite was fabricated through a facile process and its application as an excellent adsorbent for lead (II) removal was also demonstrated by applying response surface methodology (RSM). METHODS: Fe3O4@SiO2-GO nanocomposite was synthesized and characterized properly. The effects of four independent variables, initial pH of solution (3.5 8.5), nanocomposite dosage (1-60 mg L(-1)), contact time (2-30 min), and initial lead (II) ion concentration (0.5-5 mg L(-1)) on the lead (II) removal efficiency were investigated and the process was optimized using RSM. Using central composite design (CCD), 44 experiments were carried out and the process response was modeled using a quadratic equation as function of the variables. RESULTS: The optimum values of the variables were found to be 6.9, 30.5 mg L(-1), 16 min, and 2.49 mg L(-1) for pH, adsorbent dosage, contact time, and lead (II) initial concentration, respectively. The amount of adsorbed lead (II) after 16 min was recorded as high as 505.81 mg g(-1) for 90 mg L(-1) initial lead (II) ion concentration. The Sips isotherm was found to provide a good fit with the adsorption data (KS = 256 L mg(-1), nS = 0.57, qm = 598.4 mg g(-1), and R(2) = 0.984). The mean free energy Eads was 9.901 kJ/mol which confirmed the chemisorption mechanism. The kinetic study determined an appropriate compliance of experimental data with the double exponential kinetic model (R(2) = 0.982). CONCLUSIONS: Quadratic and reduced models were examined to correlate the variables with the removal efficiency of Fe3O4@SiO2-GO. According to the analysis of variance, the most influential factors were identified as pH and contact time. At the optimum condition, the adsorption yield was achieved up to nearly 100 %. PMID- 26807265 TI - Evaluation of mercury exposure level, clinical diagnosis and treatment for mercury intoxication. AB - Mercury occurs in various chemical forms, and it is different to health effects according to chemical forms. In consideration of the point, the evaluation of the mercury exposure to human distinguished from occupational and environmental exposure. With strict to manage occupational exposure in factory, it is declined mercury intoxication cases by metallic and inorganic mercury inhalation to occupational exposure. It is increasing to importance in environmental exposure and public health. The focus on the health impact of exposure to mercury is more on chronic, low or moderate grade exposure-albeit a topic of great controversy-, not high concentration exposure by methylmercury, which caused Minamata disease. Recently, the issue of mercury toxicity according to the mercury exposure level, health effects as well as the determination of what mercury levels affect health are in the spotlight and under active discussion. Evaluating the health effects and Biomarker of mercury exposure and establishing diagnosis and treatment standards are very difficult. It can implement that evaluating mercury exposure level for diagnosis by a provocation test uses chelating agent and conducting to appropriate therapy according to the result. but, indications for the therapy of chelating agents with mercury exposure have not yet been fully established. The therapy to symptomatic patients with mercury poisoning is chelating agents, combination therapy with chelating agents, plasma exchange, hemodialysis, plasmapheresis. But the further evaluations are necessary for the effects and side effects with each therapy. PMID- 26807266 TI - Rumen fermentation and performance of Hanwoo steers fed total mixed ration with Korean rice wine residue. AB - BACKGROUND: This study was conducted to evaluate the effects of adding Korean rice wine residue (RWR) in total mixed ration (TMR) on in vitro ruminal fermentation and growth performance of growing Hanwoo steers. METHODS: For in vitro fermentation, the experimental treatments were Control (Con: 0 % RWR + TMR), Treatment 1 (T1: 10 % RWR + TMR), and Treatment 2 (T2: 15 % RWR + TMR). The rumen fluid was collected from three Hanwoo steers and mixed with buffer solution, after which buffered rumen fluid was transferred into serum bottles containing 2 g dry matter (DM) of TMR added with or without RWR. The samples were then incubated for 0 h, 12 h, 24 h, or 48 h at 39 degrees C and 100 rpm. For the in vivo experiment, 27 Hanwoo steers (6 months old) with an average weight of 196 +/- 8.66 kg were subjected to a 24-week feeding trial. The animals were randomly selected and equally distributed into three groups. After which the body weight, feed intake and blood characteristics of each group were investigated. RESULTS: The pH of the treatments decreased significantly relative to the control during the 12 h of incubation. Total gas production and ammonia nitrogen (NH3-N) was not affected by RWR addition. The total volatile fatty acid (VFA) was lower after 24 h of incubation but at other incubation times, the concentration was not affected by treatments. Feed cost was 8 % and 15 % lower in T1 and T2 compared to control. Blood alcohol was not detected and a significant increase in total weight gain and average daily gain were observed in Hanwoo steers fed with RWR. CONCLUSION: Overall, the results of this study suggest that TMR amended with 15 % RWR can be used as an alternative feed resource for ruminants to reduce feed cost. PMID- 26807268 TI - Report of ITMIG 2015 Meeting. PMID- 26807267 TI - NO supplementation for transfusion medicine and cardiovascular applications. AB - Blood transfusions are used to treat reduced O2-carrying capacity consequent to anemia. In many cases anemia is caused by a major blood loss, which also creates a state of hypovolemia. Whereas O2 transport capacity is restored by increasing levels of circulating Hb, transfusion does not resolve the hypoperfusion, the hypoxia and the inflammatory cascades initiated during the anemia and hypovolemia. This explains why blood transfusion is not always an effective treatment and why transfusion of stored blood has been associated with increased morbidity and mortality, especially in patient populations receiving multiple transfusions. Epidemiologic data indicate that adverse events after transfusion are relatively common, having a great impact on the patients outcome and on the costs of public health. In this chapter, we explain why classical transfusion strategies target the reversal of hypoxia only, but do not address the inflammatory cascades initiated during anemic states and the importance of the flow and vascular endothelium interactions. We also establish the relation between red blood cells storage lesions, limited NO bioavailability and transfusion-associated adverse events. Lastly, we explain the potential use of long-lived sources of bioactive NO to reverse the hypoxic inflammatory cascades, promote a sustained increase in tissue perfusion and thereby allow transfusions to achieve their intended goal. The underlying premise is that adverse effects associated with transfusions are intimately linked to vascular dysfunction. Understanding of these mechanisms would lead to novel transfusion medicine strategies to preserve red cell function and to correct for functional changes induced by hemoglobinopathies that affect cell structure and function. PMID- 26807269 TI - Evolution of transbronchial needle aspiration technique. AB - Transbronchial needle aspiration (TBNA) is an established technique to collect cell and tissue specimens from lesions outside the airway wall, generally guided by flexible bronchoscope under the direct visualization of the puncture site. TBNA has been utilized for 30 years, and now there is renewed interest in utilizing it in conjunction with endobronchial ultrasound. Although the basic operational principles have remained the same, conventional TBNA (cTBNA) and endobronchial ultrasound-guided TBNA (EBUS-TBNA) have been greatly improved over the years with the increased application in clinic and the advance of new technology. In this article we briefly discussed the evolution of TBNA technique and its future. PMID- 26807270 TI - Evaluation of lymph node metastasis in lung cancer: who is the chief justice? AB - Accurate determination of the diagnosis and the stage of lung cancer play a critical role to ensure that patients are provided the optimal treatment. However, the process is usually beyond complex. Early studies have suggested lymph nodes (LNs) >1.0 cm in size on computed tomography (CT) are considered as metastatic nodes, while the sensitivity of this criterion is not satisfied. Subsequently, positron emission tomography-computed tomography (PET-CT) was shown to be superior to CT alone on assessment of nodal involvement and was widely used to estimate suitability for resection with curative intent, but the dependability also remains controversial. Furthermore, transbronchial needle aspiration (TBNA) with and without endobronchial ultrasound (EBUS), as a well-accepted minimally invasive approach for LN biopsy, has been documented as an efficient tool in evaluation of CT and PET-CT negative LNs. Additionally, radiographic features including ground-glass/solid nodules ratio, referring as imaging biomarker, were indicated to be correlated with metastasis. Hence, we highlight the importance of comprehensive estimation of mediastinal and hilar LNs, and we suggested the judgment of LNs by radiographic tools alone might not be reliable and TBNA is indispensable in certain circumstances. PMID- 26807271 TI - Insight into the differences in classification of mediastinal and hilar lymph nodes between Wang's lymph node map and the International Association for the Study of Lung Cancer lymph node map. AB - Lung cancer is the leading cause of malignant-tumor-related morbidity and mortality worldwide. Transbronchial needle aspiration (TBNA) has for the past 30 years been an effective technique for the diagnosis and staging of lung cancer. Understanding the anatomy of mediastinal and hilar lymph nodes is essential to improve the yield of TBNA. Wang's lymph node map is based on the lymph node map of the American Thoracic Society (ATS), and on the TBNA technique; it was published in 1994, and has promoted the development of both conventional TBNA (cTBNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). In 2009, the International Association for the Study of Lung Cancer (IASLC) developed a new chest lymph node map to reconcile the differences between the Naruke and The Mountain-Dresler (MD)-ATS lymph node maps. The IASLC lymph node map was incorporated into the seventh edition of the tumor, node, metastasis (TNM) staging system for lung cancer, which directly affected the treatment and prognosis of lung cancer. There are significant differences between Wang's lymph node map and the IASLC lymph node map in TNM staging, and it is imperative to understand these differences and correlate these maps for the prognosis and staging of lung cancer using cTBNA or EBUS-TBNA. PMID- 26807272 TI - Conventional transbronchial needle aspiration in community practice. AB - Conventional transbronchial needle aspiration (C-TBNA) provides an opportunity to diagnose mediastinal lesions and stage bronchogenic carcinoma in a minimally invasive fashion. The procedure is easy to learn and requires zero upfront cost. Any community pulmonologist can acquire and maintain the skills of C-TBNA without undergoing formal interventional pulmonary fellowship training. Besides being used for the diagnosis and staging of lung cancer, C-TBNA can be used in patients suspected to have benign conditions such as sarcoidosis and tuberculosis. It also contributes in improving the diagnostic yield of flexible bronchoscopy while dealing with endobronchial, submucosal, peribronchial, or peripheral lesions. C TBNA may be the only diagnostic modality that can be performed in patients in whom mediastinoscopy is contraindicated due to a bleeding diathesis. The procedure is safe and has great potential to augment the welfare of patients with pulmonary ailments. The learning curve of the procedure is short and steep. Every community pulmonologist should be able to perform C-TBNA. PMID- 26807273 TI - Standardized transbronchial needle aspiration procedure for intrathoracic lymph node staging of non-small cell lung cancer. AB - BACKGROUND: Thoracic lymph node (LN) metastasis is the determining factor for NSCLC staging. However, enlargement in thoracic LNs, which can be detected by chest computed tomography (CT), may not be adequate for NSCLC staging. This study aimed to investigate the effectiveness of a new transbronchial needle aspiration (TBNA) procedure to improve the sensitivity and accuracy of lung cancer diagnosis and staging. METHODS: A standardized TBNA procedure was performed on enlarged and non-enlarged LNs in the order of N3 to N1 station according to Wang's LN map. The status of LN metastasis determined by the standardized TBNA procedure was compared with the results from CT scan. RESULTS: The TBNA biopsy revealed that 21.43% of non-enlarged LNs were malignant. Compared with chest CT, the standardized TBNA procedure improved the accuracy of LN metastasis staging and discovered skip LN metastasis. CONCLUSIONS: The standardized TBNA procedure of this study may be recommended to be used as a routine TBNA procedure, in which LNs should be biopsied in the order of N3 to N1 station and both enlarged and non enlarged LNs should be included to improve the accuracy of lung cancer staging. PMID- 26807274 TI - Endobronchial ultrasound elastography: a new method in endobronchial ultrasound guided transbronchial needle aspiration. AB - BACKGROUND: TBNA through the flexible bronchoscope is a 37-year-old technology that utilizes a TBNA needle to puncture the bronchial wall and obtain specimens of peribronchial and mediastinal lesions through the flexible bronchoscope for the diagnosis of benign and malignant diseases in the mediastinum and lung. METHODS: Since 2002, the Olympus Company developed the first generation ultrasound equipment for use in the airway, initially utilizing an ultrasound probe introduced through the working channel followed by incoroporation of a fixed linear ultrasound array at the distal tip of the bronchoscope. This new bronchoscope equipped with a convex type ultrasound probe on the tip was subsequently introduced into clinical practice. The convex probe (CP)-EBUS allows real-time endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA) of mediastinal and hilar lymph nodes. EBUS-TBNA is a minimally invasive procedure performed under local anesthesia that has been shown to have a high sensitivity and diagnostic yield for lymph node staging of lung cancer. RESULTS: In 10 years of EBUS development, the Olympus Company developed the second generation EBUS bronchoscope (BF-UC260FW) with the ultrasound image processor (EU M1), and in 2013 introduced a new ultrasound image processor (EU-M2) into clinical practice. FUJI company has also developed a curvilinear array endobronchial ultrasound bronchoscope (EB-530 US) that makes it easier for the operator to master the operation of the ultrasonic bronchoscope. Also, the new thin convex probe endobronchial ultrasound bronchoscope (TCP-EBUS) is able to visualize one to three bifurcations distal to the current CP-EBUS. CONCLUSIONS: The emergence of EBUS-TBNA has also been accompanied by innovation in EBUS instruments. EBUS elastography is, then, a new technique for describing the compliance of structures during EBUS, which may be of use in the determination of metastasis to the mediastinal and hilar lymph nodes. This article describes these new EBUS techniques and reviews the relevant literature. PMID- 26807275 TI - Transbronchial needle aspiration: development history, current status and future perspective. AB - BACKGROUND: Transbronchial needle aspiration (TBNA) technology was underutilized by clinicians because it is "blind". Recent development of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) renewed the interest and confident of TBNA. TBNA without EBUS is referred as conventional transbronchial needle aspiration (C-TBNA). METHODS: This paper focuses on C-TBNA technology development history, present situation and future development to do a detailed introduction. RESULTS: TBNA is a simple, cost effective and minimally invasive technique for diagnosing disease of the mediastinum and lung in adult as well as children patients. CONCLUSIONS: More improvements of TBNA technology should be made, including employing technological advances to perfect the instruments and techniques, focusing on patient comfort, optimizing yield, simplifying instruments, maximizing ease of use and minimizing training requirements for the pulmonologist. The ideal TBNA scope deserves further evaluation and study. PMID- 26807276 TI - Endobronchial ultrasound transbronchial needle aspiration: a hybrid method. AB - BACKGROUND: Conventional transbronchial needle aspiration (cTBNA) was first performed approximately 30 years ago; however TBNA was not widely adopted until the development of endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA). Current EBUS-TBNA needle sizes are limited to 21- and 22-gauge. In order to determine whether a 19-gauge (19G) needle in EBUS-TBNA can further improve the diagnostic yield and simplify the methodology of EBUS-TBNA we developed a hybrid method. Here we report our initial experience in assessing the feasibility of performing EBUS-TBNA using a conventional 19G TBNA needle. METHODS: Ten patients with diagnosed or suspected lung cancer with or without lymphadenopathy (LAD) were sampled for diagnostic and/or staging purposes. Patients with suspected benign processes were sampled only for diagnosis. A 19G cTBNA needle was deployed through the working channel of the EBUS bronchoscope. Samples obtained were evaluated for cyto- and histopathologic adequacy. RESULTS: All 10 patients successfully underwent hybrid 19G EBUS-TBNA. All samples were considered adequate for cyto- and histopathologic evaluation. CONCLUSIONS: Hybrid EBUS-TBNA utilizing a 19G cTBNA needle through an EBUS scope is feasible and may be able to reliably acquire histologic specimens. PMID- 26807277 TI - Transthoracic needle aspiration: the past, present and future. AB - Transthoracic needle aspiration (TTNA) has been used to diagnose disease in the lung for many decades. Thanks to advances in technology and cytopathology, the diagnostic power, accuracy, safety, and efficacy of TTNA are constantly improving. The transition from fluoroscopy to computed tomography (CT) has yielded better visualization, and ability to enhance sophistication of tools used to biopsy. In addition, needles are being refined for obtaining better biopsy samples and increased capabilities. Because of the minimally invasive nature of TTNA, it is becoming a strong alternative to surgical intervention. In the future, these developments will continue and TTNA will become more efficient, and potentially open a door to personalized medicine. However, there are complications due to this procedure, which include pneumothorax, hemorrhage, air embolism, and others which are very rare. Probability of complication increases when patients are older, have significant past medical history, have larger lesions, and are uncooperative during procedure. Indications, contraindications, and other considerations should be contemplated before a patient is elected for TTNA. PMID- 26807278 TI - Transbronchial needle aspirations vs. percutaneous needle aspirations. AB - Over the last decade, the increasing diffusion of innovative and more powerful imaging guided techniques has further broadened the bronchoscopist's horizons in the diagnostic work-up of peripheral pulmonary nodules/masses (PPN/M). However, in most of institutions worldwide, due to the lack of resources and specific skills, the routinely diagnostic approach to PPN/M is still represented by imaging-guided transbronchial needle aspirations (TBNA) and percutaneous needle aspirations (PCNA). So far, no randomized clinical trials directly comparing the accuracy of the two procedures are available, and a standardized strategy that defines the proper role of each technique has yet to be established. In fact, the choice between these procedures is mostly influenced by "environmental" factors, such as operator's experience and local resources, rather than by an established algorithm, based on selected clinical scenarios. Data from literature indirectly suggest a higher sensitivity of PCNA compared to transbronchial approach, especially when lesions are peripheral and less than 2 cm. On the other hand, the transbronchial approach has been shown to have a better safety profile. Moreover, it offers the advantages to provide, during a single examination, a pathological diagnosis of nodules, information on mediastinal staging and airways involvement, and to identify potential synchronous lesions. In this context, it would be reasonable to firstly perform flexible bronchoscopy with TBNA, and, in case of inconclusive results, PCNA. In conclusions, both the techniques have been shown to be useful in the diagnostic pre-operative work-up of PPN/M. In order to optimize the diagnostic yield and to minimize the risk of patients they should not to be considered as two alternative options, but, rather, as two complementary techniques integrated in a standardized algorithm. PMID- 26807279 TI - Transthoracic needle biopsy of the lung. AB - BACKGROUND: Image guided transthoracic needle aspiration (TTNA) is a valuable tool used for the diagnosis of countless thoracic diseases. Computed tomography (CT) is the most common imaging modality used for guidance followed by ultrasound (US) for lesions abutting the pleural surface. Novel approaches using virtual CT guidance have recently been introduced. The objective of this review is to examine the current literature for TTNA biopsy of the lung focusing on diagnostic accuracy and safety. METHODS: MEDLINE was searched from inception to October 2015 for all case series examining image guided TTNA. Articles focusing on fluoroscopic guidance as well as influence of rapid on-site evaluation (ROSE) on yield were excluded. The diagnostic accuracy, defined as the number of true positives divided by the number of biopsies done, as well as the complication rate [pneumothorax (PTX), bleeding] was examined for CT guided TTNA, US guided TTNA as well as CT guided electromagnetic navigational-TTNA (E-TTNA). Of the 490 articles recovered 75 were included in our analysis. RESULTS: The overall pooled diagnostic accuracy for CT guided TTNA using 48 articles that met the inclusion and exclusion criteria was 92.1% (9,567/10,383). A similar yield was obtained examining ten articles using US guided TTNA of 88.7% (446/503). E-TTNA, being a new modality, only had one pilot study citing a diagnostic accuracy of 83% (19/23). Pooled PTX and hemorrhage rates were 20.5% and 2.8% respectively for CT guided TTNA. The PTX rate was lower in US guided TTNA at a pooled rate of 4.4%. E TTNA showed a similar rate of PTX at 20% with no incidence of bleeding in a single pilot study available. CONCLUSIONS: Image guided TTNA is a safe and accurate modality for the biopsy of lung pathology. This study found similar yield and safety profiles with the three imaging modalities examined. PMID- 26807280 TI - Navigational transbronchial needle aspiration, percutaneous needle aspiration and its future. AB - Peripheral lung nodule evaluation represents a clinical challenge. Given that many nodules will be incidentally found with lung cancer screening following the publication of the National Lung Screening Trial (NLST), the goal is to find an accurate, safe and minimally-invasive diagnostic modality to biopsy the concerning lesions. Unfortunately, conventional bronchoscopic techniques provide a poor diagnostic yield of 18-62%. In recent years advances in technology have led to the introduction of electromagnetic navigational bronchoscopy (ENB) as a tool to guide sampling of peripheral lung nodules. The same principle has also recently been expanded and applied to the transthoracic needle biopsy, referred to as electromagnetic transthoracic needle aspiration (E-TTNA). An improved diagnostic yield has afforded this technology a recommendation by the 2013 3(rd) Edition ACCP Guidelines for the Diagnosis and Management of Lung Cancer which state that "in patients with peripheral lung lesions difficult to reach with conventional bronchoscopy, ENB is recommended if the equipment and the expertise are available (Grade 1C)". In this review we will discuss the technology, devices that are available, techniques and protocols, diagnostic yield, safety, cost effectiveness and more. PMID- 26807281 TI - The past, current and future of diagnosis and management of pleural disease. AB - Pleural disease is frequently encountered by the chest physician. Pleural effusions arise as the sequelae of underlying disease processes including pressure/volume imbalances, infection and malignancy. In addition to pleural effusions, persistent air leaks after surgery and bronchopleural fistulae remain a challenge. Our understanding of pleural disease including its diagnosis and management, have made tremendous strides. The introduction of the molecular detection of organism specific infection, risk stratification and improvements in the non-surgical treatment of patients with pleural infection are all within reach and may be the standard of care in the very near future. Malignant pleural effusion management continues to evolve with the introduction of tunneled pleural catheters and procedures combining that and chemical pleurodesis. These advances in the diagnostic and therapeutic evaluation of pleural disease as well as what seems to be an increasing multidisciplinary interest in the space foretell a bright future. PMID- 26807282 TI - Thoracoscopy: medical versus surgical-in the management of pleural diseases. AB - Diseases of the pleura continue to affect a large population of patients worldwide and in the United States. Pleural fluid analysis and accompanying imaging of the pleura including chest X-rays, chest computed tomography (CT) scan and chest ultrasonography are among the first steps in the management of pleural effusions. When further diagnostic or therapeutic work up is necessary, open thoracotomy and thoracoscopy come to mind. However, given the significant morbidity and mortality associated with open thoracotomy, and the advances in medicine and medical instruments, thoracoscopy has now become a routine procedure in the management of the disease of the chest including pleura. Debates about surgical vs. medical thoracoscopy (MT) are ongoing. In the following pages we review the literature and discuss the similarities and differences between the two procedures, as well as their indications, contraindications, complications and efficacy in the management of pleural diseases. PMID- 26807283 TI - Rigid bronchoscopy and silicone stents in the management of central airway obstruction. AB - The field of interventional pulmonology has grown significantly over the past several decades now including the diagnosis and therapeutic treatment of complex airway disease. Rigid bronchoscopy is an invaluable tool in the diagnosis and management of several malignant and non-malignant causes of central airway obstruction (CAO) and has become integral after the inception of airway stenting. The management of CAO can be a complicated endeavor with significant risks making the understanding of basic rigid bronchoscopy techniques, ablative technologies, anesthetic care and stenting of utmost importance in the care of these complex patients. This review article will focus on the history of rigid bronchoscopy, the technical aspects of performing a rigid bronchoscopy as well as the use of silicone stents their indications, complications and placement techniques. PMID- 26807285 TI - Past, present, and future of endobronchial laser photoresection. AB - Laser photoresection of central airway obstruction is a useful tool for an Interventional Pulmonologist (IP). Endobronchial therapy of the malignant airway obstruction is considered as a palliative measure or a bridge therapy to the definite treatment of cancer. Several ablative therapies such as electrocautery, argon plasma coagulation (APC), cryotherapy and laser photoresection exist in the armamentarium of IP to tackle such presentations. Besides Neodymium-Yttrium, Aluminum, Garnet (Nd:YAG) laser, there are several different types of laser that have been used by the pulmonologist with different coagulative and cutting properties. This chapter focuses on the historical perspective, current status, and potentials of lasers in the management of central airway lesions. PMID- 26807286 TI - The treatment strategy for tracheoesophageal fistula. AB - With the development of endoscopic techniques, the treatment of tracheoesophageal fistula (TEF) has made marked progress. As surgical intervention is often not an advisable option due to advanced malignancy and poor performance status of the patients, bronchoscopic intervention provides a good choice to palliate symptoms and reconstruct the airway and esophagus. In this review, we focus on the application of interventional therapy of TEF, especially the application of airway stenting, and highlight some representative cases referred to our department for treatment. PMID- 26807284 TI - From electrocautery, balloon dilatation, neodymium-doped:yttrium-aluminum-garnet (Nd:YAG) laser to argon plasma coagulation and cryotherapy. AB - Over the past decade, there has been significant advancement in the development/application of therapeutics in thoracic diseases. Ablation methods using heat or cold energy in the airway is safe and effective for treating complex airway disorders including malignant and non-malignant central airway obstruction (CAO) without limiting the impact of future definitive therapy. Timely and efficient use of endobronchial ablative therapies combined with mechanical debridement or stent placement results in immediate relief of dyspnea for CAO. Therapeutic modalities reviewed in this article including electrocautery, balloon dilation (BD), neodymium-doped:yttrium-aluminum-garnet (Nd:YAG) laser, argon plasma coagulation (APC), and cryotherapy are often combined to achieve the desired results. This review aims to provide a clinically oriented review of these technologies in the modern era of interventional pulmonology (IP). PMID- 26807288 TI - Spray cryotherapy (SCT): institutional evolution of techniques and clinical practice from early experience in the treatment of malignant airway disease. AB - BACKGROUND: Spray cryotherapy (SCT) was initially developed for gastroenterology (GI) endoscopic use in the esophagus. In some institutions where a device has been utilized by GI, transition to use in the airways by pulmonologists and thoracic surgeons occurred. Significant differences exist, however, in the techniques for safely using SCT in the airways. METHODS: We describe the early experience at Walter Reed National Military Medical Center from 2011 to 2013 using SCT in patients with malignant airway disease and the evolution of our current techniques and clinical practice patterns for SCT use in patients. In November 2013 enrollment began in a multi-institutional prospective SCT registry in which we are still enrolling and will be reported on separately. RESULTS: Twenty-seven patients that underwent 80 procedures (2.96 procedures/patient). The average age was 63 years with a range of 20 to 87 years old. The average Eastern Cooperative Oncology Group (ECOG) status was 1.26. All malignancies were advanced stage disease. All procedures were performed in the central airways. Other modalities were used in combination with SCT in 31 (39%) of procedures. Additionally 45 of the 80 (56%) procedures were performed in proximity to a silicone, hybrid, or metal stent. Three complications occurred out of the 80 procedures. All three were transient hypoxia that limited continued SCT treatments. These patients were all discharged from the bronchoscopy recovery room to their pre-surgical state. CONCLUSIONS: SCT can be safely used for treatment of malignant airway tumor (MAT) in the airways. Understanding passive venting of the nitrogen gas produced as the liquid nitrogen changes to gas is important for safe use of the device. Complications can be minimized by adopting strict protocols to maximize passive venting and to allow for adequate oxygenation in between sprays. PMID- 26807287 TI - Temporary placement of metallic stent could lead to long-term benefits for benign tracheobronchial stenosis. AB - BACKGROUND: The permanent placement of metallic stent for benign tracheobronchial stenosis (BTS) was controversial. This study was conducted to evaluate the long term outcomes of temporary placement of metallic stent for BTS. METHODS: The BTS patients who received temporary placement of retrievable self-expanded metallic stents were included between 2008 and 2011. Pre-stenting and follow-up respiratory status was analyzed. And symptom recurrence-free survival (SRFS) was assessed. RESULTS: A total of 49 stents were successfully temporarily placed in 40 consecutive BTS patients whose etiologies included endobronchial tuberculosis (EBTB) (n=22), post-tracheostomy stenosis (n=10), post-intubation stenosis (n=6) and post radiotherapy stricture (n=2). All stents were removed integrally after a median 18 days' stenting period, without major complications. During the median 27 months follow-up period after stent removal, a total of 22 patients were free of recurrence. And the overall 3-year SRFS rate was 52.0%. According to the etiology, the 3-year SRFS rates were 59.1% and 42.9% in the patients with EBTB and non-EBTB, respectively. Compared with pre-stenting, the follow-up internal diameter of stricture, Hugh-Jones scale, 6-minute walk test (6MWT) and percentage of forced expiratory volume in one second (FEV1%) were significantly improved. Multivariate analysis suggested that granulation tissue growth and tracheobronchial malacia might be independent factors of poor prognosis. CONCLUSIONS: Temporary placement of retrievable metallic stent may be an alternative treatment for BTS patients. PMID- 26807289 TI - Training program of interventional pulmonology fellowships: USA. AB - Interventional pulmonary (IP) is an emerging subspecialty of pulmonary medicine which focuses on procedures of the airway, lung, and pleura. As the number of advance procedures increases with the growth of this field, additional formal training is required to offer the full complement of techniques. IP fellowship is a dedicated 12 months fellowship in the United States which occurs after pulmonary/critical care fellowship. There have been several recent milestones in this field which include validated exams based on didactic knowledge and structural organization of fellowship organizations. PMID- 26807290 TI - Improved diagnostic yield of bronchoscopy in peripheral pulmonary lesions: combination of radial probe endobronchial ultrasound and rapid on-site evaluation. AB - BACKGROUND: Rapid on-site evaluation (ROSE) of cytologic specimens is a useful ancillary technique in needle aspiration procedures of pulmonary/mediastinal lesions, but few reports had been carried out to confirm the utility in the diagnosis of peripheral pulmonary lesions (PPLs) by radial probe endobronchial ultrasound (R-EBUS). METHODS: To evaluate the impact of ROSE on the diagnostic yield of R-EBUS for PPLs, we retrospectively analyzed the diagnostic yields of transbronchial biopsy (TBB) or brushing using R-EBUS for patients with PPLs in a tertiary university hospital from December 2012 to December 2014. RESULTS: A total of 815 patients with PPLs were included. A definite diagnosis was made by R EBUS-guided TBB or brushing for 627 patients (76.9%). A total of 279 patients (34.2%) were examined by a ROSE technique. The combination of R-EBUS guided TBB or brushing with ROSE raised the diagnostic yield in the diagnosis of PPLs, especially difficult cases: right apical and left apical-posterior segment locations, small PPLs <3 cm without bronchus signs on computed tomography (CT) scan, PPLs with pleural effusions, and the position of probe is not within. CONCLUSIONS: ROSE can improve the PPLs diagnostic yield when using R-EBUS guided TBB or brushing. PMID- 26807291 TI - Molecular Genetic Testing in Pain and Addiction: Facts, Fiction and Clinical Utility. AB - The Brain Reward Cascade (BRC) is an interaction of neurotransmitters and their respective genes to control the amount of dopamine released within the brain. Any variations within this pathway, whether genetic or environmental (epigenetic), may result in addictive behaviors as well as altered pain tolerance. While there are many studies claiming a genetic association with addiction and other behavioral infractions, defined as Reward Deficiency Syndrome (RDS), not all are scientifically accurate and in some case just wrong. Albeit our bias, we discuss herein the facts and fictions behind molecular genetic testing in RDS (including pain and addiction) and the significance behind the development of the Genetic Addiction Risk Score (GARSPREDXTM), the first test to accurately predict one's genetic risk for RDS. PMID- 26807292 TI - An additional ultrasonographic sign of Hashimoto's lymphocytic thyroiditis in children. AB - We present an additional sonographic sign of Hashimoto's thyroiditis (HLT), increasing the specificity of this method in pediatric populations. METHODS: A total of 98 children (mean age 12.7 years, range 7-17 years) were selected from the registry of the endocrinology outpatient department. All subjects met the diagnostic criteria for HLT. All children underwent a prospective thyroid ultrasound examination with special attention paid to the presence of lymph nodes adjacent to the thyroid gland. In order to form a control group, we analyzed 102 healthy volunteers and 94 children with cervical lymphadenopathy, age- and sex matched with the main study group. RESULTS: The ultrasound of the thyroid revealed typical sonographic signs of autoimmune thyroid disease in all children with HLT and in none of the individuals in the control groups. In 96 children (98%) from the HLT group, at least 2 lymph nodes adjacent to the lower part of the thyroid gland lobes localized on one or both sides of the thyroid were detected. No lymph nodes adjacent to the lower part of the thyroid lobes were found in healthy children or children with cervical lymphadenopathy. CONCLUSIONS: Lymph nodes adjacent to the lower part of the thyroid lobes are an additional ultrasound sign of pediatric Hashimoto's lymphocytic thyroiditis, with 98% sensitivity and 100% specificity. PMID- 26807293 TI - Shear wave elastography in medullary thyroid carcinoma diagnostics. AB - Shear wave elastography (SWE) is a modern method for the assessment of tissue stiffness. There has been a growing interest in the use of this technique for characterizing thyroid focal lesions, including preoperative diagnostics. AIM: The aim of the study was to assess the clinical usefulness of SWE in medullary thyroid carcinoma (MTC) diagnostics. MATERIALS AND METHODS: A total of 169 focal lesions were identified in the study group (139 patients), including 6 MTCs in 4 patients (mean age: 45 years). B-mode ultrasound and SWE were performed using Aixplorer (SuperSonic, Aix-en-Provence), with a 4-15 MHz linear probe. The ultrasound was performed to assess the echogenicity and echostructure of the lesions, their margin, the halo sign, the height/width ratio (H/W ratio), the presence of calcifications and the vascularization pattern. This was followed by an analysis of maximum and mean Young's (E) modulus values for MTC (EmaxLR, EmeanLR) and the surrounding thyroid tissues (EmaxSR, EmeanSR), as well as mean E values (EmeanLRz) for 2 mm region of interest in the stiffest zone of the lesion. The lesions were subject to pathological and/or cytological evaluation. RESULTS: The B-mode assessment showed that all MTCs were hypoechogenic, with no halo sign, and they contained micro- and/ or macrocalcifications. Ill-defined lesion margin were found in 4 out of 6 cancers; 4 out of 6 cancers had a H/W ratio > 1. Heterogeneous echostructure and type III vascularity were found in 5 out of 6 lesions. In the SWE, the mean value of EmaxLR for all of the MTCs was 89.5 kPa and (the mean value of EmaxSR for all surrounding tissues was) 39.7 kPa Mean values of EmeanLR and EmeanSR were 34.7 kPa and 24.4 kPa, respectively. The mean value of EmeanLRz was 49.2 kPa. CONCLUSIONS: SWE showed MTCs as stiffer lesions compared to the surrounding tissues. The lesions were qualified for fine needle aspiration biopsy based on B-mode assessment. However, the diagnostic algorithm for MTC is based on the measurement of serum calcitonin levels, B-mode ultrasound and FNAB. PMID- 26807294 TI - Echogenicity of benign adrenal focal lesions on imaging with new ultrasound techniques - report with pictorial presentation. AB - AIM: The aim of the research was to assess the echogenicity of benign adrenal focal lesions using new ultrasound techniques. MATERIAL AND METHOD: 34 benign adrenal masses in 29 patients were analyzed retrospectively. The examinations were conducted using Aplio XG (Toshiba, Japan) ultrasound scanner with a convex probe 1-6 MHz in the B-mode presentation with the combined use of new ultrasound techniques: harmonic imaging and spatial compound sonography. The size of the adrenal tumors, their echogenicity and homogeneity were analyzed. Statistical analysis was conducted using the STATISTICA 10 software. RESULTS: The following adrenal masses were assessed: 12 adenomas, 10 nodular hyperplasias of adrenal cortex, 7 myelolipomas, 3 pheochromocytomas, a hemangioma with hemorrhage and a cyst. The mean diameter of nodular hyperplasia of adrenal cortex was not statistically different from that of adenomas (p = 0.075). The possibility of differentiating between nodular hyperplasia and adenoma using the parameter of hypoechogenicity or homogeneity of the lesion was demonstrated with the sensitivity and specificity of 100% and 41.7%, respectively. The larger the benign adrenal tumor was, the more frequently did it turn out to have a mixed and inhomogenous echogenicity (p < 0.05; ROC areas under the curve: 0.832 and 0.805, respectively). CONCLUSIONS: A variety of echogenicity patterns of benign adrenal focal lesions was demonstrated. The image of an adrenal tumor correlates with its size. The ultrasound examination, apart from its indisputable usefulness in detecting and monitoring adrenal tumors, may also allow for the differentiation between benign lesions. However, for lesions found incidentally an algorithm for the assessment of adrenal incidentalomas is applicable, which includes computed tomography and magnetic resonance imaging. PMID- 26807295 TI - Standards of ultrasound imaging of the adrenal glands. AB - Adrenal glands are paired endocrine glands located over the upper renal poles. Adrenal pathologies have various clinical presentations. They can coexist with the hyperfunction of individual cortical zones or the medulla, insufficiency of the adrenal cortex or retained normal hormonal function. The most common adrenal masses are tumors incidentally detected in imaging examinations (ultrasound, tomography, magnetic resonance imaging), referred to as incidentalomas. They include a range of histopathological entities but cortical adenomas without hormonal hyperfunction are the most common. Each abdominal ultrasound scan of a child or adult should include the assessment of the suprarenal areas. If a previously non-reported, incidental solid focal lesion exceeding 1 cm (incidentaloma) is detected in the suprarenal area, computed tomography or magnetic resonance imaging should be conducted to confirm its presence and for differentiation and the tumor functional status should be determined. Ultrasound imaging is also used to monitor adrenal incidentaloma that is not eligible for a surgery. The paper presents recommendations concerning the performance and assessment of ultrasound examinations of the adrenal glands and their pathological lesions. The article includes new ultrasound techniques, such as tissue harmonic imaging, spatial compound imaging, three-dimensional ultrasound, elastography, contrast-enhanced ultrasound and parametric imaging. The guidelines presented above are consistent with the recommendations of the Polish Ultrasound Society. PMID- 26807296 TI - Doppler imaging of orbital vessels in the assessment of the activity and severity of thyroid-associated orbitopathy. AB - Patients with symptoms of thyroid-associated orbitopathy are classified on the basis of the clinical activity score (CAS) proposed by Mourits in 1989. Despite its undoubted clinical usefulness, it has several limitations which can decide about the success or failure of the implemented treatment. Numerous reports mention the presence of hemodynamic changes in orbital and bulbar vessels in the course of an orbitopathy called Graves' disease. The usage of Doppler sonography in the diagnosis of numerous ophthalmologic vascular diseases suggests that changes in thyroid-associated orbitopathy can correlate with the activity and severity of the disease. This paper presents the overview of the state-of-the-art concerning the usefulness of Doppler imaging in patient selection for the treatment of thyroid-associated orbitopathy. It has been shown that the velocity of blood flow in the superior ophthalmic vein, which is the most susceptible to changes in anatomical conditions in the enclosed orbital space, decreases in a statistically significant way. A decrease in blood flow velocity is closely associated with the active stage of the disease whereas reverse flow or its absence attest to severe orbitopathy and constitute a risk factor of ocular neuropathy. The activity of the inflammatory process in the eyeball is also confirmed by an increase in peak systolic velocity (PSV) in the ophthalmic artery and central retinal artery as well as end-diastolic velocity (EDV) in the ophthalmic artery. Resistance index values decrease in the ophthalmic artery and increase in the central retinal artery mainly in cases with considerable expansion of the extraocular muscles. PMID- 26807297 TI - The role of ultrasound and nuclear medicine methods in the preoperative diagnostics of primary hyperparathyroidism. AB - Primary hyperparathyroidism (PH) represents one of the most common endocrine diseases. In most cases, the disorder is caused by parathyroid adenomas. Bilateral neck exploration has been a widely used treatment method for adenomas since the 20's of the twentieth century. In the last decade, however, it has been increasingly replaced by a minimally invasive surgical treatment. Smaller extent, shorter duration and lower complication rate of such a procedure are emphasized. Its efficacy depends on a precise location of parathyroid tissue during the preoperative imaging. Scintigraphy and ultrasound play a major role in the diagnostic algorithms. The efficacy of both methods has been repeatedly verified and compared. The still-current guidelines of the European Association of Nuclear Medicine (2009) emphasize the complementary role of scintigraphy and ultrasonography in the preoperative diagnostics in patients with primary hyperparathyroidism. At the same time, attempts are made to improve both these techniques by implementing new study protocols or innovative technologies. Publications have emerged in the recent years in the field of ultrasonography, whose authors pointed out the usefulness of elastography and contrast media. Nuclear medicine studies, on the other hand, focus mainly on the assessment of new radiotracers used in the positron emission tomography (PET). The aim of this article is to present, based on literature data, the possibilities of ultrasound and scintigraphy in the preoperative diagnostics in patients with primary hyperparathyroidism. Furthermore, the main directions in the development of imaging techniques in PH patients were evaluated. PMID- 26807298 TI - Value of ultrasonography in the diagnosis of polycystic ovary syndrome - literature review. AB - Polycystic ovary syndrome is a multi-factorial disease. Its etiopathogenesis has not been elucidated in detail. It is the most common endocrine disorder in women of child-bearing age. This disease entity is primarily characterized by disrupted ovulation and hyperandrogenism, but the clinical picture can be diversified and symptom intensity can vary. Currently, the sonographic assessment of ovaries is one of the obligatory criteria for the diagnosis of PCOS according to the Rotterdam consensus (2003) and Androgen Excess & PCOS Society (2006). This criterion is determined by the presence of >=12 follicles within the ovary with a diameter of 2-9 mm and/or ovarian volume >=10 cm(3). Such an ultrasound image in one gonad only is sufficient to define polycystic ovaries. The coexistence of polycystic ovaries with polycystic ovary syndrome is confirmed in over 90% of cases irrespective of ethnic factors or race. However, because of the commonness of ultrasound features of polycystic ovaries in healthy women, the inclusion of this sign to the diagnostic criteria of polycystic ovary syndrome is still questioned. The development of new technologies has an undoubted influence on the percentage of diagnosed polycystic ovaries. This process has caused an increase in the percentage of polycystic ovary diagnoses since the Rotterdam criteria were published. It is therefore needed to prepare new commonly accepted diagnostic norms concerning the number of ovarian follicles and the standardization of the technique in which they are counted. The assessment of anti-Mullerian hormone levels as an equivalent of ultrasound features of polycystic ovaries is a promising method. However, analytic methods have to be standardized in order to establish commonly accepted diagnostic norms. PMID- 26807299 TI - Ultrasound image of the thyroid gland in obese children. AB - Obesity as a disease of affluence also affects younger children. Numerous observations suggest a link between excessive body weight and thyroid function disorders. Subclinical hypothyroidism has been diagnosed increasingly frequently in patients with obesity. A growing number of papers also point to morphological changes of the thyroid gland in the ultrasound examination in obese children. These reports mainly concern changes in echogenicity. The present paper discusses the most important aspects of this topic on the basis of the literature as well as containing a brief analysis based on own experiences. PMID- 26807300 TI - Adrenal abscess in a 3-week-old neonate - a case report. AB - The authors present a case of a 6-year-old boy operated on in the 4th week of life because of adrenal abscess. The diagnosis of an adrenal abscess in the neonatal period is challenging due to its rare occurrence and non-specific signs. Adrenal abscesses can develop via two mechanisms: as a result of a hematogenic infection and a spread of bacteria to "normal" adrenal glands or, which is much more common, a complication of an adrenal hematoma. Early and accurate diagnosis is crucial for appropriate therapeutic management. Imaging, including ultrasound, can be problematic. The final diagnosis is frequently established on the basis of a histological examination of a surgical specimen. PMID- 26807301 TI - Contralateral adrenal metastasis from renal cell carcinoma with tumor thrombus in the adrenal vein: a case report. AB - A 64-year-old woman presented with contralateral right adrenal metastasis with adrenal vein thrombus, which was diagnosed many years after left nephrectomy with adrenalectomy due to renal cell cancer. The patient underwent right adrenalectomy with adrenal vein tumor thrombectomy for treatment. The pathologic examination confirmed metastatic clear cell carcinoma. The remote but existing risk of developing contralateral adrenal metastasis (CAM) after primary radical nephrectomy supports the idea of sparing the adrenal gland in suitable patients who undergo radical nephrectomy. Contralateral adrenal metastasis from RCC is a rare finding with the potential benefit of cure after resection. Care must be taken in preoperative diagnostics, as this metastasis is capable of causing inferior vena cava tumor thrombus via the suprarenal venous route. According to our knowledge, our case is the second similar entity described in literature so far. PMID- 26807303 TI - A new species of Agaricus section Minores from China. AB - Agaricus gemloides sp. nov. is characterised by its reddish brown fibrillose squamose on the pileus, relatively slender basidiome and broader basidiospores. In this article, it is introduced based on its distinguished morphological features and molecular phylogenetic position. PMID- 26807302 TI - Primary Biliary Cirrhosis Overlapping with Autoimmune Hepatitis in an HIV Infected Patient on Antiretroviral Therapy. AB - Liver disease in HIV-infected patients is complex and multifactorial. Drug toxicity and infections are common causes of elevations in liver-associated enzymes. Immune reconstitution and unmasking of autoimmune disease may also play a role, particularly in the era of effective combination antiretroviral therapy. In this case report, we describe the first reported biopsy-confirmed case of autoimmune hepatitis and primary biliary cirrhosis overlap syndrome presenting in an HIV-infected patient following initiation of antiretroviral therapy. PMID- 26807304 TI - Methotrexate as a Corticosteroid-Sparing Agent for Thyroid Eye Disease. AB - OBJECTIVE: Thyroid eye disease (TED) is generally treated with oral corticosteroid therapy. A steroid sparing drug could be a useful adjunct. We reviewed our experience with methotrexate as a corticosteroid sparing agent to treat TED. METHODS: Retrospective chart review from two eye inflammation clinics. Patients with TED who were unable to discontinue prednisone therapy without disease recurrence were included. RESULTS: 14 patients who were receiving an average of 32 mg/day of prednisone were treated with methotrexate, usually 15 mg/week orally or 20 mg/week subcutaneously. Five patients discontinued therapy for a lack of benefit or intolerance. Of the 9 patients who remained on methotrexate, all were able to discontinue prednisone completely after an average duration of 7.5 months. Improved visual acuity by at least two lines on the Snellen chart was achieved by 7 of 12 patients with reduced acuity and partial improvement in ocular motility was achieved in 5 of 14 patients. CONCLUSIONS: Methotrexate provided an effective steroid sparing effect in a subset of patients with TED. PMID- 26807305 TI - Imbalance of the Nerve Growth Factor and Its Precursor: Implication in Diabetic Retinopathy. AB - Diabetic retinopathy is the leading cause of blindness in working age in US and worldwide. Neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) are known to be essential for growth, differentiation and survival of neurons in the developing and mature retina. Nevertheless, a growing body of evidence supports an emerging role of neurotrophins in retinal diseases and in particular, diabetic retinopathy. Neurotrophins are initially synthesized in a pro-form and undergo proteolytic cleavage to produce the mature form that activates two distinctive receptors, the tyrosine kinase tropomycin receptor (Trk) and, to lesser extent, the common low affinity p75 neurotrophin receptor (p75NTR). Despite tight glycemic and metabolic control, many diabetic patients continue to experience progressive retinal damage. Understanding the molecular events involved in diabetic retinopathy is extremely important to identify novel therapeutic strategies to halt the disease progression. Diabetes induces imbalance in neurotrophins by increasing its proform, which is associated with upregulation of the p75NTR receptor in the retina. A growing body of evidence supports a link between the imbalance of pro-neurotrophins and early retinal inflammation, neuro and microvascular degeneration. Therefore, examining changes in the levels of neurotrophins and its receptors might provide a therapeutically beneficial target to combat disease progression in diabetic patients. This commentary aims to highlight the impact of diabetes-impaired balance of neurotrophins and in particular, the NGF and its receptors; TrkA and p75NTR in the pathology of DR. PMID- 26807306 TI - Pressure-Induced Alterations in PEDF and PEDF-R Expression: Implications for Neuroprotective Signaling in Glaucoma. AB - INTRODUCTION: Alterations in neuron-glia signaling are implicated in glaucoma, a neurodegenerative disease characterized by retinal ganglion cell (RGC) death. Pigment epithelium derived factor (PEDF) is a secreted protein with potential neuroprotective qualities in retinal disease, including chronic ocular hypertension. Here we sought to determine whether moderate, short-term elevations in IOP alter PEDF signaling and whether pressure-induced PEDF signaling directly impacts RGC apoptosis. METHODS: In retina from naive mice and mice with unilateral, microbead-induced glaucoma, we examined expression and cell type specific localization of PEDF and its receptor (PEDF-R), using quantitative PCR and immunohistochemistry. Using primary cultures of purified RGCs and Muller cells, we examined cell type-specific expression of PEDF in response to 48 hours of elevated hydrostatic pressure, using multiplex ELISA and immunocytochemistry. We also measured pressure-induced apoptosis of RGCs in the presence or absence of atglistatin, a potent and selective inhibitor of PEDF-R, and recombinant PEDF, using TUNEL assays. RESULTS: PEDF and PEDF-R are constitutively expressed in naive retina, primarily in the ganglion cell and nerve fiber layers. Elevated IOP increases PEDF and PEDF-R expression, particularly associated with RGCs and Muller cells. Elevated pressure in vitro increased PEDF secretion by 6-fold in RGCs and trended towards an increase in expression by Muller cells, as compared to ambient pressure. This was accompanied by changes in the subcellular localization of PEDF-R in both cell types. Inhibition of PEDF signaling with atglistatin increased pressure-induced apoptosis in RGCs and treatment with recombinant PEDF inhibited pressure-induced apoptosis, both in a dose-dependent manner. CONCLUSION: Our findings suggest that moderate, short-term elevations in IOP promote PEDF signaling via up-regulation of both PEDF and PEDF-R. Based on in vivo and in vitro studies, this PEDF signaling likely arises from both Muller cells and RGCs, and has the potential to directly inhibit RGC apoptosis. PMID- 26807307 TI - Staphylococcal Enterotoxin B (SEB) Induces Memory CD4 T Cell Anergy in vivo and Impairs Recall Immunity to Unrelated Antigens. AB - INTRODUCTION: Naive and memory T cells can utilize unique regulatory pathways to promote protection but prevent self-reactivity. A bacterial superantigen SEB exploits unique TCR proximal signaling processes in memory CD4 T cells to induce clonal anergy. The aim of this study was to determine if SEB could antagonize memory CD4 T cells in vivo and whether there would be consequences on recall immune responses. We evaluated Ab responses to a T-dependent antigen as a measurement of memory T cell helper function. METHOD: BALB/c mice were primed with TNP-RGG to elicit memory B cells and also immunized with an ovalbumin peptide to elicit memory helper T cells. Another group of TNP-RGG immunized mice were used as adoptive transfer recipients of exogenous DO11.10 memory T cells. Mice were challenged with TNP-OVA with or without prior administration of SEB. B cells secreting IgM or IgG TNP-specific Ab were enumerated by ELISPOT as indicators of primary versus secondary humoral immunity. RESULTS: Comparing the SEB and non-SEB-treated groups, the SEB-treated group failed to produce TNP specific IgG in response to challenge with TNP-OVA, even if they were previously immunized with OVA. All groups produced IgM, indicating that the primary Ab responses and naive helper T cells were not impacted by SEB. SEB had no negative impact when DO11.10 * Fyn-/- memory T cells were used as donor cells. CONCLUSION: The present study indicated that SEB selectively targeted memory CD4 T cells in vivo and prevented helper function. Consequently, recall humoral immunity was lost. The data are most consistent with in vivo T cell anergy as opposed to indirect suppression as elimination of Fyn kinase restored helper function. These data suggest that bacterial superantigens can impair post-vaccination memory cell responses to unrelated antigens via their ability to target Vb families and antagonize memory cell activation. PMID- 26807309 TI - miR-24 Regulates Macrophage Polarization and Plasticity. AB - OBJECTIVE: MicroRNAs (miRNA) are ubiquitous regulators of human biology and immunity. Previously, we have demonstrated an inhibitory role for miR-24 in the phagocytosis of Escherichia coli and Staphylococcus aureus bioparticles and the induction of cytokine secretion in response to lipopolysaccharide (LPS) of the same origin; also, we have identified divergent and convergent miRNA responses to LPS from the periodontopathic pathogens Aggregatibacter actinomycetemcomitams (Aa) and Porphyromonas gingivalis (Pg), and revealed cigarette smoke extract as an environmental modifier of Pg LPS structure (Pg CSE) impacting macrophage miRNA responses. This study was designed to investigate the role of miR-24 on macrophage polarization and plasticity. METHODS: Primary human macrophages were differentiated from CD14+ monocytes isolated from peripheral blood mononuclear cells (PBMCs) by MACS positive selection and transfected with miR-24 miRNA mimics, inhibitors, or negative control mimic; followed by stimulation with cytokines and/or LPS under various conditions representing key stages of macrophage activation. Macrophage activation and polarization was assessed using assays for cytokine production (ELISA) and protein expression (flow cytometry, immunoblot). MiR-24 expression was assessed by RT-PCR. RESULTS: Stimulation of macrophages with LPSs of Aa, Pg, and Pg CSE origin resulted in dissimilar levels of cytokine expression and differential expression of miR-24. Overexpression of miR-24 inhibited cytokine secretion in response to LPS. Priming of macrophages with interferon gamma (IFN-gamma) did not overcome this inhibitory effect, but classical activation of macrophages with IFN-gamma plus TNF-alpha, TNF-beta, or IL-17, modulated the pattern of miR-24 mediated suppression in a cytokine specific fashion. Overexpression of miR-24 enhanced CD206 upregulation during alternative macrophage activation and inhibited its downregulation in macrophage transitioning from alternative to classical activation states. Overexpression of miR-24 resulted in reduced expression of the Class 1A PI 3-kinase subunit p110 delta (p110delta). CONCLUSION: Pathogen- and environment-specific modifications in LPS alter the expression of cytokines and miR-24 in human macrophages. MiR-24 is a negative regulator of macrophage classical activation by LPS and promotes alternative activation under conditions of polarization and plasticity. MiR-24 mediated inhibition of LPS-induced cytokine secretion is dependent upon macrophage activation state at the point of stimulation, and this may be due to the degree to which p110delta is involved in the intracellular signaling pathway/s that transduce receptor ligation into cytokine induction. While important differences were observed in the effect of miR-24 on macrophages, these data indicate that overexpression of miR-24 would be predominantly anti inflammatory. PMID- 26807308 TI - Prostate Cancer Immunotherapy: Exploiting the HLA Class II Pathway in Vaccine Design. AB - Prostate cancer is the second most diagnosed cancer in men and current treatment of advanced prostate cancer is ineffective. Immunotherapy has emerged as a promising treatment option for metastatic prostate cancer but its clinical application is still in the early stages of development. In order to treat metastatic prostate tumors, new directions must be taken to improve current immunotherapeutic strategies. These include the identification of effective tumor antigens (Ags), the induction of the HLA class II pathway for Ag processing and CD4+ T cell activation, and the ability of tumor cells to act like Ag presenting cells. In this review, we suggest a model for tumor Ag selection, epitope modification and self-processing for presentation by class II proteins as a means of restoring immune activation and tumor clearance. We also outline the importance of a Gamma-IFN-inducible Lysosomal Thiol reductase (GILT) in Ag and modified peptide processing by tumor cells, generation of functional epitopes for T cell recognition, and inclusion of immune checkpoint blockers in cancer immunotherapy. Taken together, this review provides a framework for the future development of novel cancer vaccines and the improvement of existing immunotherapeutics in prostate cancer. PMID- 26807310 TI - Effects of radiation on T regulatory cells in normal states and cancer: mechanisms and clinical implications. AB - Radiation remains an important component of cancer treatment. In addition to inducing tumor cell death through direct cytotoxic effects, radiation can also promote the regression of tumor via augment of immune response. Regulatory T cells (Tregs) are a unique subpopulation of CD4 positive cells, which are characterized by expression of the forkhead box P3 (Foxp3) transcription factor and high levels of CD25. Mounting evidence has shown that Tregs are implicated in the development and progression of various types of cancer, which makes Tregs an important target in cancer therapeutics. Generally, lymphocytes are regarded as radiosensitive. However, Tregs have been demonstrated to be relatively resistant to radiotherapy, which is partly mediated by downregulation of pro-apoptotic proteins and upregulation of anti-apoptotic proteins. Moreover, radiotherapy can increase the production of Tregs and the recruitment of Tregs to local tumor microenvironment. Tregs can attenuate radiation-induced tumor death, which cause the resistance of tumor to radiotherapy. Recent experimental studies and clinical trails have demonstrated that the combination of radiation with medications that target Tregs is promising in the treatment of several types of neoplasms. In this review, we discussed the effect of radiation on Tregs in physiological states and cancer. Further, we presented an overview of therapies that target Tregs to enhance the efficacy of radiation in cancer therapeutics. PMID- 26807311 TI - Impact of prospero homeobox-1 on tumor cell behavior and prognosis in colorectal cancer. AB - Prospero homeobox 1 (PROX1) is up-regulated in colorectal cancer and plays an oncogenic role. In the present study, we sought to investigate the impact of PROX1 on oncogenic processes and to assess the prognostic value of PROX1 expression in colorectal cancer. A small interfering RNA or pcDNA6-myc vector was used to control PROX1 gene expression in colorectal cancer DLD1 and SW480 cell lines. The expression of PROX1 in colorectal cancer tissues was investigated by immunohistochemistry. Angiogenesis, lymphangiogenesis, and tumor cell proliferation were assessed by analyzing the expression of respective markers of these phenomena, CD34, D2-40, and Ki-67 after immunohistochemical staining. PROX1 knockdown decreased both umbilical vein endothelial cell invasion and tube formation, down-regulated the expression of VEGF-A and HIF-1alpha, and up regulated the expression of angiostatin. Lymphatic endothelial cell invasion and tube formation as well as the expression of VEGF-C were also suppressed by PROX1 knockdown. PROX1 knockdown suppressed tumor cell proliferation, migration, invasion, and epithelial-mesenchymal transition. In contrast, PROX1 overexpression enhanced tumor cell angiogenesis, lymphangiogenesis, proliferation, migration, invasion, and epithelial-mesenchymal transition. Levels of phosphorylated Akt, GSK3beta, and MAPK were decreased by PROX1 knockdown and increased by PROX1 overexpression. PROX1 expression positively correlated with tumor size, extent of differentiation, lymphovascular invasion, depth of invasion, lymph node metastasis, stage, and poor survival. The mean microvessel density and Ki-67 labeling index values of PROX1-positive tumors were significantly higher than those of PROX1-negative tumors. However, there was no significant correlation between PROX1 expression and lymphatic vessel density. These results indicate that PROX1 influences tumor progression in colorectal cancer by regulating angiogenesis and tumor cell proliferation. PMID- 26807312 TI - Radiolabeling and evaluation of (64)Cu-DOTA-F56 peptide targeting vascular endothelial growth factor receptor 1 in the molecular imaging of gastric cancer. AB - Noninvasive imaging of vascular endothelial growth factor receptor 1 (VEGFR1) remains a great challenge in early diagnosis of gastric cancer. Here we reported the synthesis, radiolabeling, and evaluation of a novel (64)Cu-radiolabeled peptide for noninvasive positron emission tomography (PET) imaging of VEGFR1 positive gastric cancer. The binding of modified peptide WHSDMEWWYLLG (termed as F56) to VEGER-1 expressed in gastric cancer cell BCG823 has been confirmed by immune-fluorescence overlap. DOTA-F56 was designed and prepared by solid-phase synthesis and folded in vitro. (64)Cu-DOTA-F56 was synthesized in high radiochemical yield and high specific activity (S.A. up to 255.6 GBq/mmol). It has excellent in vitro stability. Micro-PET imaging of (64)Cu-DOTA-F56 identifies tumor in BCG823 tumor-bearing mice, while that of (18)F-FDG does not. Immunohistochemical analysis of excised BCG823 xenograft showed colocalization between the PET images and the staining of VEGFR1. These results demonstrated that (64)Cu-DOTA-F56 peptide has potential as a noninvasive imaging agent in VEGFR1 positive tumors. PMID- 26807313 TI - Sildenafil inhibits the growth of human colorectal cancer in vitro and in vivo. AB - Colorectal cancer is the third most common human cancer with frequent overexpression of the cGMP-specific phosphodiesterase 5 (PDE5). In the present study, we investigated that the anticancer effect of sildenafil on human colorectal cancer in vitro and in vivo, which is a potent and selective inhibitor of PDE5 for the treatment of erectile dysfunction and pulmonary arterial hypertension in the clinic. Sildenafil significantly induced cell growth inhibition, cell cycle arrest and apoptosis of human colorectal cancer with increased intracellular reactive oxidative specie (ROS) levels, which were accompanied by obvious alterations of related proteins such as CDKs, Cyclins and PARP etc. Pretreatment with ROS scavenger N-acetyl-L-cysteine could reverse sildenafil-induced ROS accumulation and cell apoptosis. Inhibition of the activity of protein kinase G with KT-5823 could enhance sildenafil-induced apoptosis. Furthermore, sildenafil caused the reduction of xenograft models of human colorectal cancer in nude mice. Overall, these findings suggest that sildenafil has the potential to be used for treatment of human colorectal cancer. PMID- 26807314 TI - Therapeutic intervention of proanthocyanidins on the migration capacity of melanoma cells is mediated through PGE2 receptors and beta-catenin signaling molecules. AB - Melanoma is a highly aggressive form of skin cancer and a leading cause of death from skin diseases mainly due to its propensity to metastasis. Due to metastatic tendency, melanoma is often associated with activation of Wnt/beta-catenin signaling mechanism. Blocking beta-catenin activation may be a good strategy to block melanoma-associated mortality. We have shown earlier that grape seed proanthocyanidins (GSPs) inhibit melanoma cell migration via targeting cyclooxygenase-2 (COX-2) overexpression. Here we explored further whether inhibition of inflammatory mediators-mediated activation of beta-catenin by GSPs is associated with the inhibition of melanoma cell migration. Our study revealed that PGE2 receptors (EP2 and EP4) agonists promote melanoma cell migration while PGE2 receptor antagonist suppressed the migration capacity of melanoma cells. GSPs treatment inhibit butaprost (EP2 agonist) or Cay10580 (EP4 agonist) induced migration of melanoma cells. Western blot analysis revealed that GSPs reduced cellular accumulation of beta-catenin, and decreased the expressions of matrix metalloproteinase (MMP)-2, MMP-9 and MITF, downstream targets of beta-catenin in melanoma cells. GSPs also reduced the protein expressions of PI3K and p-Akt in the same set of experiment. To verify that beta-catenin is a specific molecular target of GSPs, we compared the effect of GSPs on cell migration of beta-catenin activated (Mel1241) and beta-catenin-inactivated (Mel1011) melanoma cells. GSPs inhibit cell migration of Mel1241 cells but not of Mel1011 cells. Additionally, in vivo bioluminescence imaging data indicate that dietary administration of GSPs (0.5%, w/w) in supplementation with AIN76A control diet inhibited the migration/extravasation of intravenously injected melanoma cells in lungs of immune-compromised nude mice, and that this effect of GSPs was associated with an inhibitory effect on the activation of beta-catenin and its downstream targets, such as MMPs, in lungs as a target organ. PMID- 26807315 TI - Targeting oncogenic KRAS in non-small cell lung cancer cells by phenformin inhibits growth and angiogenesis. AB - Tumors require a vascular supply to grow and can achieve this via the expression of pro-angiogenic growth factors. Many potential oncogenic mutations have been identified in tumor angiogenesis. Somatic mutations in the small GTPase KRAS are the most common activating lesions found in human cancer, and are generally associated with poor response to standard therapies. Biguanides, such as the diabetes therapeutics metformin and phenformin, have demonstrated anti-tumor activity both in vitro and in vivo. The extracellular regulated protein kinases (ERK) signaling is known to be a major cellular target of biguanides. Based on KRAS activates several down-stream effectors leading to the stimulation of the RAF/mitogen-activated protein kinase/extracellular signal-regulated kinase (RAF/MEK/ERK) and phosphatidylinositol-3-kinase (PI3K) pathways, we investigated the anti-tumor effects of biguanides on the proliferation of KRAS-mutated tumor cells in vitro and on KRAS-driven tumor growth in vivo. In cancer cells harboring oncogenic KRAS, phenformin switches off the ERK pathway and inhibit the expression of pro-angiogenic molecules. In tumor xenografts harboring the KRAS mutation, phenformin extensively modifies the tumor growth causing abrogation of angiogenesis. These results strongly suggest that significant therapeutic advantage may be achieved by phenformin anti-angiogenesis for the treatment of tumor. PMID- 26807316 TI - MLN4924, a Novel NEDD8-activating enzyme inhibitor, exhibits antitumor activity and enhances cisplatin-induced cytotoxicity in human cervical carcinoma: in vitro and in vivo study. AB - MLN4924, an inhibitor of NEDD8 activating enzyme (NAE), has been reported to have activity against various malignancies. Here, we investigated the antitumor properties of MLN4924 and MLN4924 in combination with cisplatin on human cervical carcinoma (CC) in vitro and in vivo. Two human CC cell lines, ME-180 and HeLa, were used in this study. The cytotoxic effects of MLN4924 and/or cisplatin were measured by cell viability (MTT), proliferation (BrdU incorporation), apoptosis (flow cytometry with annexin V-FITC labeling), and the expression of cell apoptosis-related proteins (Western blotting). In vivo efficacy was determined in Nu/Nu nude mice with ME-180 and HeLa xenografts. The results showed that MLN4924 elicited viability inhibition, anti-proliferation and apoptosis in human CC cells, accompanied by activations of apoptosis-related molecules and Bid, Bcl-2 phosphorylation interruption, and interference with cell cycle regulators. Moreover, MLN4924 caused an endoplasmic reticulum stress response (caspase-4, ATF 4 and CHOP activations) and expression of other cellular stress molecules (JNK and c-Jun activations). Additionally, MLN4924 suppressed growth of CC xenografts in nude mice. Furthermore, we demonstrated that MLN4924 potentiated cisplatin induced cytotoxicity in CC cells with activation of caspases. Consistently with this, MLN4924 significantly enhanced cisplatin-induced growth inhibition of CC xenografts. Together, these findings suggest that MLN4924 alone or in combination with cisplatin is of value in treating human CCs. PMID- 26807317 TI - The added value of circulating tumor cells examination in ovarian cancer staging. AB - Delayed diagnosis of ovarian cancer (OC) is usually a cause of its high mortality. OC counts for one of the most aggressive gynecological malignancies. Noninvasive biomarkers may be used to help with diagnostic and treatment decisions in OC management. The incidence and clinical significance of occult OC cells (circulating tumor cells-CTCs) in the peripheral blood of patients with newly diagnosed or nondiagnosed OC at the time of surgical intervention were examined in our study. The objective of the study was to isolate and cultivate CTCs in OC patients (mainly stage IIIB-C) by a recently introduced size-based separation method (MetaCell((r))). CTCs were successfully isolated in patients with OC capturing cells with proliferation potential. The cells were enriched in good fitness, which enabled the short term in vitro culture of the CTCs. The CTCs may be used for further downstream applications (e.g. gene expression analysis) even if in the majority of the in vitro CTC cultures no confluence was reached. The CTCs were detected in 77 out of 118 patients (65.2%). CTC positivity was given to the relationship with different disease stage parameters with special focus on CA125 marker levels. The results show that the information on CTC presence may provide new and independent prognosis staging information to the patient description. Several interesting relationships of CA125, age and ascites presence are reported. As shown in our patient sample, patients with ascites tend to have higher CA125 levels, even if the CTCs were not found in the peripheral blood. It suggests that hematogenous dissemination is fully represented by the CTCs while lymphogenic dissemination is represented by elevated CA125. In this context, easy access to CTCs provided by the method applied in our study, both at the time of diagnosis and relapse, may become an increasingly valuable tool in future. This methodology may provide an opportunity for more personalized medicine where treatment for OC may be guided by information from an individual's CTC molecular profile. PMID- 26807318 TI - The distinct signatures of VEGF and soluble VEGFR2 increase prognostic implication in gastric cancer. AB - Recently, an anti-angiogenic strategy to treat gastric cancer (GC) has been successful with the use of ramucirumab. The comprehensive network of VEGF, soluble VEGF receptor-2 (sVEGFR2) and cytokines and other angiogenic factors (CAF) in GC has not been reported. We aimed to reveal the CAF signature associated with VEGF and sVEGFR2, and to explore their prognostic implication in GC. We measured pretreatment serum levels of 52 CAFs, including VEGF and sVEGFR2, using multiplex bead immunoassays and ELISA, in 70 GC patients treated with palliative chemotherapy. Linear regression analysis for correlating CAFs with VEGF and sVEGFR2, and survival analysis were performed. Results from the current analysis showed the VEGF signature was shown to be associated with seven CAFs (IL 7, IL-12p70, IL-2Ra, IL-10, stem cell factor, FGF2b, IL-3). The sVEGFR2 signature was associated with IL-4 and PDGFb. VEGF and sVEGFR2 showed no association with each other. High VEGF was associated with worse OS (11.2 months, high-VEGF versus 16.7 months, low-VEGF; P = 0.061). However, among patients with high-sVEGFR2, OS was not different according to VEGF (12.1 months, high-VEGF versus 15.1 months, low-VEGF; P = 0.546). In patients with low-sVEGFR2, OS was significantly different according VEGF (10.9 months, high-VEGF versus 16.8 months, low-VEGF, P = 0.036). In multivariate analysis, a high VEGF/sVEGFR2 ratio was significantly correlated with worse OS (HR 1.78 [95% CI 1.08-2.94], P = 0.024). In conclusion, VEGF and sVEGFR2 had distinct CAF signatures in GC. Consideration of both VEGF and sVEGFR2 confers more accurate prognostic implication compared with VEGF alone in GC. PMID- 26807319 TI - Association of EP2 receptor and SLC19A3 in regulating breast cancer metastasis. AB - Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer patients have higher metastatic rate than patients with other breast cancer subtypes. Distant metastasis is one of the causes leading to the high mortality rates. Cyclooxygenase-2 (COX2) is associated with breast cancer metastasis and the downstream prostaglandin E2 (PGE2) exerted its effect through EP receptors (EP1-EP4). However, the exact molecular events of EP receptors in breast cancer metastasis remain undefined. Expressions of EP receptors were determined during cancer development in NOD-SCID mice inoculated with MB-231 and MB-231-EP2 clone. EP2 overexpressing stable clone was constructed to investigate the proliferation and invasion potentials in vivo and in vitro. Drug transporter array was used to identify EP2 receptor-associated drug transported genes in breast cancer metastasis. Localization of EP2 receptor in primary tissues and xenografts were examined by immunostaining. Stable EP2-expression cells formed larger tumors than parental cells in mice model and was highly expressed in both primary and metastatic tissues. Silencing of EP2 receptor by siRNA and antagonist (AH 6809) significantly decreased cell proliferation and invasion, concomitant with reduced MMP-2 and MMP-9 expressions. Results from array data showed that expression of SLC19A3 was markedly increased in EP2 siRNA transfected cells. Ectopic expression of SLC19A3 retarded cell proliferation, invasion and MMPs expressions. Notably, SLC19A3 had a lower expression in primary tissues and was negatively correlated with EP2 receptor expression. Our novel finding revealed that EP2 receptor regulated metastasis through downregulation of SLC19A3. Thus, targeting EP2-SLC19A3 signaling is a potential therapeutic therapy for treating metastatic breast cancer. PMID- 26807320 TI - Molecular dynamics simulation on the low sensitivity of mutants of NEDD-8 activating enzyme for MLN4924 inhibitor as a cancer drug. AB - MLN4924 is an experimental cancer drug known as inhibitor of NEDD8-activating enzyme (NAE). This anti-tumor candidate is a selective small-molecule inhibitor of NAE which is conjugated to cullin protein on Cullin-RING ligases (CRLs). This covalent modification actives cullin complex to recruit an ubiquitin-charged E2 and leads to downstream target protein polyubiquitination and proteasomal degradation. MLN4924, which can form a covalent adduct with NEDD8, and block NAE at the first step in this pathway, has shown anti-tumor activity in many kinds of cancer cell lines and also xenograft models, including lung cancer, colon cancer, melanoma and lymphoma. The anti-tumor activity of MLN4924 results from inactivation of CLRs, which causes DNA re-replication and inhibition of nuclear factor (NF)-kappaB signaling, thus leading to cancer cell death. A mutation can reduce the enzyme's sensitivity to MLN4924. Verma et al. in 2013 studied on molecular dynamics simulation of a mutant A171T and consequently found out that this mutation reduce MLN4924 interaction with DNA Binding site of enzyme as a result of reduction of enzyme affinity to ATP. One year later, in 2014, Wei Xu et al. carried out a research on inhibitor resistant cell lines and revealed that a couple of mutations so called Y352H and I310N leads to enzyme resistance to MLN4924 inhibitor, interestingly, the cause reported was the increase of enzyme affinity to ATP. As in Wei Xu et al. experiment the molecular dynamics simulation was not considered, present study is conducted to identify enzyme mutation mechanism by molecular dynamics approach using advantages of Gromacs software version 4.5.6. PMID- 26807321 TI - Basic helix loop helix (bHLH) transcription factor 3 (TCF3, E2A) is regulated by androgens in prostate cancer cells. AB - TCF3 (E2A) is a multifunctional basic helix loop helix (bHLH) transcription factor that is over-expressed in prostate cancer (PCa) as compared to normal prostate and that it acts as a tumor promoter in PCa. Given the diverse biological pathways regulated/influenced by TCF3, little is known about the mechanisms that regulate its expression. TCF3 expression in androgen sensitive LNCaP and insensitive C81 PCa cell lines was determined following treatments with androgen receptor (AR) agonist R1881 and antagonist Casodex. In silico analysis was used to discover putative Androgen Response Elements (ARE) in the TCF3 promoter/intron region. Chromatin Immunoprecipitation (ChIP) with AR antibody and luciferase reporter assays on the above mentioned cell lines was used to confirm AR biding and AR dependent transcriptional activity respectively. The results were confirmed by demonstrating TCF3 expression in LNCaP PCa xenograft models. The results suggested that TCF3 transcript increased in response to R1881 in LNCaP cells but was constitutively expressed in C-81 cell lines. The promoter/Intron region of the TCF3 gene was predicted to contain two putative ARE sites ARE1 and ARE2. ChIP after treatment of LNCaP and C81 cells with R1881 and Casodex showed that the ARE1 and ARE2 were bound by AR in LNCaP cells only in the presence of R1881, whereas C81 cells showed constitutive AR binding. Similar results were observed in luciferase reporter assays indicating that TCF3 is activated by AR in LNCaP cell lines whereas it is independent of androgens in C81 cell line. Luciferase reporter assays also confirmed that ARE1 alone drives androgen dependent transcription. TCF3 expression was only observed in castration resistant LNCaP xenografts in castrated mice. In conclusion, we demonstrate that in PCa androgen receptor regulates the expression of TCF3 which is mediated in part via a consensus androgen response element. The shift in TCF3 expression from androgen regulated to androgen independent during prostate cancer progression, together with lack of expression in normal prostate may provide mechanistic basis underlying the transition of androgen receptor from a tumor suppressor to an oncogene in prostate cancer. PMID- 26807322 TI - Tumor-selective anti-cancer effects of the synthetic alkyl phosphocholine analog CLR1404 in neuroblastoma. AB - Neuroblastoma (NB) is the most common extracranial solid tumor in children and is associated with high mortality in advanced stages. Survivors suffer from long term treatment-related sequelae. Thus, new targeted treatment options are urgently needed. 18-(p-[(127)I] iodophenyl) octadecyl phosphocholine (CLR1404) is a novel, broadly tumor targeted small molecule drug suitable for intravenous injection with highly selective tumor uptake. As a carrier molecule for radioactive iodine, CLR1404 is in clinical trials as cancer imaging agent and radiotherapeutic drug. Chemically, CLR1404 belongs to the anti-tumor alkyl phospholipids, a class of drugs known to have intrinsic cytotoxic effects on cancer cells. Therefore, we hypothesized that CLR1404 could be a tumor-targeted anti-cancer agent for neuroblastoma, and investigated its effect in vitro and in vivo. CLR1404 was taken up by NB cells in a highly tumor-selective manner both in vitro and in vivo, confirmed by flow cytometry and PET/CT imaging of mouse flank xenografts with (124)I-CLR1404, respectively. Using flow cytometry, MTT assay, Western blotting and caspase 3/7 assay, we confirm that in vitro treatment with CLR1404 leads to robust apoptosis and cell death in multiple NB cell lines and is associated with Akt inhibition, while sparing normal cells. Treatment with CLR1404 in doses of 10 or 30 mg/kg administered by intravenous injection once weekly for 7 weeks significantly inhibited the tumor growth rate in a mouse flank xenograft model of NB (P<0.001) when compared to control cohorts, without causing drug-related hematotoxicity or other noticeable adverse effects, which was determined by serial tumor volume measurements, complete blood counts, and monitoring of animal-specific health parameters. We conclude that CLR1404 warrants clinical exploration as a novel, tumor selective anticancer agent in NB and potentially other cancers. PMID- 26807323 TI - Impaired TGF-beta induced growth inhibition contributes to the increased proliferation rate of neural stem cells harboring mutant p53. AB - Gliomas have been classified according to their histological properties. However, their respective cells of origin are still unknown. Neural progenitor cells (NPC) from the subventricular zone (SVZ) can initiate tumors in murine models of glioma and are likely cells of origin in the human disease. In both, p53 signaling is often functionally impaired which may contribute to tumor formation. Also, TGF beta, which under physiological conditions exerts a strong control on the proliferation of NPCs in the SVZ, is a potent mitogen on glioma cells. Here, we approach on the crosstalk between p53 and TGF-beta by loss of function experiments using NPCs derived from p53 mutant mice, as well as pharmacological inhibition of TGF-beta signaling using TGF-beta receptor inhibitors. NPC derived from p53 mutant mice showed increased clonogenicity and more rapid proliferation than their wildtype counterparts. Further, NPC derived from p53(mut/mut) mice were insensitive to TGF-beta induced growth arrest. Still, the canonical TGF-beta signaling pathway remained functional in the absence of p53 signaling and expression of key proteins as well as phosphorylation and nuclear translocation of SMAD2 were unaltered. TGF-beta-induced p21 expression could, in contrast, only be detected in p53(wt/wt) but not in p53(mut/mut) NPC. Conversely, inhibition of TGF-beta signaling using SB431542 increased proliferation of p53(wt/wt) but not of p53(mut/mut) NPC. In conclusion, our data suggest that the TGF-beta induced growth arrest in NPC depends on functional p53. Mutational inactivation of p53 hence contributes to increased proliferation of NPC and likely to the formation of hyperplasia of the SVZ observed in p53 deficient mice in vivo. PMID- 26807324 TI - Tissue and serum IGFBP7 protein as biomarker in high-grade soft tissue sarcoma. AB - Soft-tissue sarcomas (STS) are a heterogeneous group of mesenchymal tumors whose classification and treatment is complicated by molecular heterogeneity within the histological subtypes and by the lack of prognostic/therapeutic biomarkers. This study analyses expression of target proteins involved in insulin-like growth factor pathway (IGF1Rbeta, IRS1 S612 and IGFBP7) in high-grade STS to stratify patients with the worst prognosis. Tissue microarray analysis performed on 145 high-grade STS samples revealed a uniform expression of IGF1Rbeta and IRS1 S612, while IGFBP7 was more strongly expressed in metastatic than in metastasis-free patients. This was confirmed by multivariate regression analysis that demonstrated the independent poor prognostic role of IGFBP7 overexpression with a significant increase of risk of metastasis (HR = 6.358, 95% CI = 2.946-13.721; P < 0.0005). Given the evidence that circulating protein may generate from tissue tumor cells, in 59/145 patients who had available serum we measured IGFBP7 concentration. The ELISA assay revealed significantly higher levels in tumor patients than in the control with a possible threshold value of 25 ng/ml. Differentiating sera according to primary tumor histotype, significantly higher IGFBP7 concentration was found in synovial sarcoma and liposarcoma than in other STS histotypes. This study revealed that tissue expression of IGFBP7, considered a tumor stroma marker in mesenchymal derived cells, was highly prognostic in poor metastasis-free survival. In parallel, the determination of serum protein levels might contribute to STS diagnosis. Subsequent analyses will be crucial to understand the clinical relevance of IGFBP7 protein in STS. PMID- 26807325 TI - Noninvasive urinary miRNA biomarkers for early detection of pancreatic adenocarcinoma. AB - Currently, the majority of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) present with locally invasive and/or metastatic disease, resulting in five-year survival of less than 5%. The development of an early diagnostic test is, therefore, expected to significantly impact the patient's prognosis. In this study, we successfully evaluated the feasibility of identifying diagnostic cell free microRNAs (miRNAs) for early stage PDAC, through the analysis of urine samples. Using Affymetrix microarrays, we established a global miRNA profile of 13 PDAC, six chronic pancreatitis (CP), and seven healthy (H) urine specimens. Selected differentially expressed miRNAs were subsequently investigated using an independent technique (RT-PCR) on 101 urine samples including 46 PDAC, 29 CP and 26 H. Receiver operating characteristic (ROC) and logistic regression analyses were applied to determine the discriminatory potential of the candidate miRNA biomarkers. Three miRNAs (miR-143, miR-223, and miR-30e) were significantly over-expressed in patients with Stage I cancer when compared with age-matched healthy individuals (P=0.022, 0.035 and 0.04, respectively); miR-143, miR-223 and miR-204 were also shown to be expressed at higher levels in Stage I compared to Stages II-IV PDAC (P=0.025, 0.013 and 0.008, respectively). Furthermore, miR-223 and miR-204 were able to distinguish patients with early stage cancer from patients with CP (P=0.037 and 0.036). Among the three biomarkers, miR-143 was best able to differentiate Stage I (n=6) from healthy (n=26) with area under the curve (AUC) of 0.862 (95% CI 0.695-1.000), with sensitivity (SN) of 83.3% (95% CI 50.0-100.0), and specificity (SP) of 88.5% (95% CI 73.1-100.0). The combination of miR-143 with miR-30e was significantly better at discriminating between these two groups, achieving an AUC of 0.923 (95% CI 0.793-1.000), with SN of 83.3% (95% CI 50.0-100.0) and SP of 96.2% (95% CI 88.5-100.0). In this feasibility study, we demonstrate for the first time the utility of miRNA biomarkers for non-invasive, early detection of PDAC in urine specimens. PMID- 26807326 TI - Correlations between U.S. county annual cancer incidence and population density. AB - Population density implicitly involves specific distances between living individuals who exhibit biophysical forces and energies. Objective was to investigate major data bases of cancer incidence and population data to help understand the emergent properties of diseases that become apparent only when large populations and areas are considered. Correlation analyses of the annual incidence (years 2007 to 2011) of cancer in counties (2,885) of the U.S. and population densities were convergent with these quantitative predictions and suggested an inflection threshold around 50 people per square mile. The potential role of subtle or even "non-local" factors coupled to averaged population density in the viability and mortality of the human species may serve as alternative explanations to the attribution of malignancy to "chance" factors. Calculations indicated average distances between the electric force dipole of the brains or bodies of human beings generate forces known to affect DNA extension and when distributed over the Compton wavelength of the electron could produce energies sufficient to affect the binding of base nucleotides. An inclusive science of human ecology might benefit from considering subtle forces and energies associated with the individual members within the habitat that could determine the probability of cellular anomalies. PMID- 26807327 TI - Effects of EZH2 promoter polymorphisms and methylation status on oral squamous cell carcinoma susceptibility and pathology. AB - Oral squamous cell carcinoma (OSCC), which is malignant tumors in oral cavity, is the fourth most common male cancer in Taiwan. EZH2 plays a key role in transcriptional repression through chromatin remodeling and in cancer development. Although the EZH2 expression in OSCC is highly correlated with tumorigenesis, it has not been determined if specific EZH2 genetic variants are associated with OSCC risk. The aim of this study was to investigate the relationship between genetic polymorphisms of EZH2 and susceptibility to OSCC in Taiwan. Here, four SNPs of EZH2 (rs6950683, rs2302427, rs3757441, and rs41277434) were analyzed by a real-time PCR genotyping in 576 patients with oral cancer and 552 cancer-free controls. After adjusting for other co-variants, we found that carrying CC genotype at EZH2 rs6950683 and rs3757441 had a lower risk of developing OSCC than did wild-type carriers. The CCCA or CCTA haplotype among the four EZH2 sites was also associated with a reduced risk of OSCC. Furthermore, OSCC patients who carried CC genotype at EZH2 rs6950683 had a higher methylation than TC genotype. Our results suggest that the two SNPs of EZH2 (rs6950683 and rs3757441) might contribute to the prediction of OSCC susceptibility. Moreover, rs6950683 CC genotype exhibits hypermethylation in EZH2 promoter. This is the first study to provide insight into risk factors associated with EZH2 variants and epigenetic changes in carcinogenesis of OSCC in Taiwan. PMID- 26807328 TI - Mediated coalescence: a possible mechanism for tumor cellular heterogeneity. AB - Recently, we demonstrated that tumorigenic cell lines and fresh tumor cells seeded in a 3D Matrigel model, first grow as clonal islands (primary aggregates), then coalesce through the formation and contraction of cellular cables. Non tumorigenic cell lines and cells from normal tissue form clonal islands, but do not form cables or coalesce. Here we show that as little as 5% tumorigenic cells will actively mediate coalescence between primary aggregates of majority non tumorigenic or non-cancerous cells, by forming cellular cables between them. We suggest that this newly discovered, specialized characteristic of tumorigenic cells may explain, at least in part, why tumors contain primarily non-tumorigenic cells. PMID- 26807329 TI - Differential Properties of Human ALP+ Periodontal Ligament Stem Cells vs Their ALP- Counterparts. AB - Characterizing subpopulations of stem cells is important to understand stem cell properties. Tissue-nonspecific alkaline phosphatase (ALP) is associated with mineral tissue forming cells as well as stem cells. Information regarding ALP subpopulation of human periodontal ligament stem cells (hPDLSCs) is limited. In the present study, we examined ALP+ and ALP- hPDLSC subpopulations, their surface markers STRO-1 and CD146, and the expression of stemness genes at various cell passages. We found that ALP+ subpopulation had higher levels of STRO-1 (30.6 +/- 5.6%) and CD146 (90.4 +/- 3.3%) compared to ALP- (STRO-1: 0.5 +/- 0.1%; CD146: 75.3 +/- 7.2%). ALP+ cells expressed significantly higher levels of stemness associated genes, NANOG, OCT4 and SOX than ALP- cells at low cell passages of 2-3 (p<0.05). ALP+ and ALP- cells had similar osteogenic, chondrogenic and neurogenic potential while ALP-, not ALP+ cells, lacked adipogenic potential. Upon continuous culturing and passaging, ALP+ continued to express higher stemness genes and STRO-1 and CD146 than ALP- cells at >=passage 19. Under conditions (over-confluence and vitamin C treatment) when ALP+ subpopulation was increased, the stemness gene levels of ALP+ was no longer significantly higher than those in ALP- cells. In conclusion, ALP+ hPDLSCs possess differential properties from their ALP- counterparts. PMID- 26807330 TI - Sources of Disability in Tourette Syndrome: Children vs. Adults. AB - BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by tics and neuropsychiatric co-morbidities like Obsessive Compulsive Disorder (OCD) and Attention Deficit Disorder (ADHD), among others. In many instances tics get better with age but this is not always true regarding the psychiatric co morbidities. METHODS: This manuscript reviews the disease-specific Quality of Life (QOL) instruments used to measure disability in TS and the existing literature on sources of functional impairment in children and adults with TS. RESULTS: Traditionally, disability in TS has been recorded using objective measures. In recent years there has been a development of disease-specific instruments to measure subjectively the impact of the different aspects of TS on the patient's daily function. The differential impact of tics vs. the psychiatric co-morbidities in children with TS is an issue of debate in the existing literature. In adults with TS, the literature is scant, therefore the sources of disability in this group are even less defined compared to children. DISCUSSION: As clinicians, we need to focus on determining the sources of disability in children and adults with TS so we can target our interventions successfully. PMID- 26807331 TI - Epigenomic Indicators of Age in African Americans. AB - Age is a well-established risk factor for chronic diseases. However, the cellular and molecular changes associated with aging processes that are related to chronic disease initiation and progression are not well-understood. Thus, there is an increased need to identify new markers of cellular and molecular changes that occur during aging processes. In this study, we use genome-wide DNA methylation from 26,428 CpG sites in 13,877 genes to investigate the relationship between age and epigenetic variation in the peripheral blood cells of 972 African American adults from the Genetic Epidemiology Network of Arteriopathy (GENOA) study (mean age=66.3 years, range=39-95). Age was significantly associated with 7,601 (28.8%) CpG sites after Bonferroni correction for alpha=0.05 (p<1.89*10-6). Due to the extraordinarily strong associations between age and many of the CpG sites (>7,000 sites with p-values ranging from 10-6 to 10-43), we investigated how well the DNA methylation markers predict age. We found that 2,095 (7.9%) CpG sites were significant predictors of age after Bonferroni correction. The top five principal components of the 2,095 age-associated CpG sites accounted for 69.3% of the variability in these CpG sites, and they explained 26.8% of the variation in age. The associations between methylation markers and adult age are so ubiquitous and strong that we hypothesize that DNA methylation patterns may be an important measure of cellular aging processes. Given the highly correlated nature of the age-associated epigenome (as evidenced by the principal components analysis), whole pathways may be regulated as a consequence of aging. PMID- 26807333 TI - Characterization of intracranial atherosclerotic stenosis using high-resolution MRI study--rationale and design. AB - BACKGROUND: Intracranial atherosclerosis is a leading cause of stroke, but little is known about the composition of the intracranial atherosclerotic lesion and how intracranial plaque morphology is related to the risk of stroke. High-resolution magnetic resonance imaging (HR MRI) has been used in patients with extracranial carotid atherosclerosis as an in vivo tool to identify, with high-interrater agreement, histologically defined plaque components (i.e., intraplaque hemorrhage, fibrous cap, and lipid core), which have been shown to be predictors of recurrent stroke. With careful imaging the components of atherosclerotic plaque can be visualized in the intracranial arteries using HR MRI, but there are no reports of reproducibility or interrater reliability. METHODS/STUDY DESIGN: The Characterization of intracranial atherosclerotic stenosis using high resolution MRI (CHIASM) study is a single-center NIH-funded prospective observational study, to (1) demonstrate high -interrater agreement for identifying intracranial plaque components on HR MRI, (2) determine the frequency of these components in symptomatic versus asymptomatic plaques, and (3) estimate the 1-year rate of stroke in the territory of high-risk plaque components. CHIASM will recruit 90 patients with 50-99% intracranial atherosclerosis to undergo HRMRI of the intracranial artery plaque at enrollment and 1-year follow-up. Both symptomatic and asymptomatic subjects will be recruited. CONCLUSION: Determination of good interrater reliability is an important first step in the development of HR MRI as a tool to predict risk in patients with intracranial atherosclerosis. This study will inform the design of future multicenter studies to determine the prevalence and prognosis of intracranial atherosclerotic plaque components. Such studies could lead to new understanding of the pathophysiological mechanisms of cerebral ischemia in patients with atherosclerotic intracranial stenosis, improvements in risk stratification, and potentially to new treatments of this common and serious disease. PMID- 26807332 TI - A semi-supervised Support Vector Machine model for predicting the language outcomes following cochlear implantation based on pre-implant brain fMRI imaging. AB - INTRODUCTION: We developed a machine learning model to predict whether or not a cochlear implant (CI) candidate will develop effective language skills within 2 years after the CI surgery by using the pre-implant brain fMRI data from the candidate. METHODS: The language performance was measured 2 years after the CI surgery by the Clinical Evaluation of Language Fundamentals-Preschool, Second Edition (CELF-P2). Based on the CELF-P2 scores, the CI recipients were designated as either effective or ineffective CI users. For feature extraction from the fMRI data, we constructed contrast maps using the general linear model, and then utilized the Bag-of-Words (BoW) approach that we previously published to convert the contrast maps into feature vectors. We trained both supervised models and semi-supervised models to classify CI users as effective or ineffective. RESULTS: Compared with the conventional feature extraction approach, which used each single voxel as a feature, our BoW approach gave rise to much better performance for the classification of effective versus ineffective CI users. The semi supervised model with the feature set extracted by the BoW approach from the contrast of speech versus silence achieved a leave-one-out cross-validation AUC as high as 0.97. Recursive feature elimination unexpectedly revealed that two features were sufficient to provide highly accurate classification of effective versus ineffective CI users based on our current dataset. CONCLUSION: We have validated the hypothesis that pre-implant cortical activation patterns revealed by fMRI during infancy correlate with language performance 2 years after cochlear implantation. The two brain regions highlighted by our classifier are potential biomarkers for the prediction of CI outcomes. Our study also demonstrated the superiority of the semi-supervised model over the supervised model. It is always worthwhile to try a semi-supervised model when unlabeled data are available. PMID- 26807335 TI - Sonographic examination of the median nerve in dialysis patients and after renal transplantation. AB - OBJECTIVE: Patients with renal insufficiency are predisposed to develop CTS (carpal tunnel syndrome). In particular, long-term dialysis seems to contribute to changes in median nerve texture which lead to an increased risk for CTS. The current study was designed to evaluate if these structural changes can be detected by HRS (high-resolution sonography). Additionally, the current study aimed to determine if changes are reversible after termination of dialysis. METHODS: Fifty patients (98 hands) were included in the study. The study population was subdivided into three groups: patients without any history of renal disease (H, n = 20), patients with long-term dialysis (D, n = 10), and patients after renal transplantation (TX, n = 20). None of the patients had any clinical symptoms for a median nerve compression syndrome. The CSA (cross sectional area) of the median nerve was evaluated both 12 cm proximally of the carpal tunnel inlet and directly at the carpal tunnel inlet. The ratio of those two values, the WFR (wrist forearm ratio), was calculated and analyzed. RESULTS: The CSA demonstrated significantly higher values in dialysis (D) and transplanted (TX) patients compared to the healthy (H) control group (P < 0.001). No significant differences were detectable between the D and TX groups. Specifically, there was no significant difference in the WFR. CONCLUSION: Patients with chronic renal disease demonstrate significantly higher CSA values compared to their healthy counterparts. Termination of dialysis does not seem to reverse these morphological changes. PMID- 26807334 TI - A postnatal peak in microglial development in the mouse hippocampus is correlated with heightened sensitivity to seizure triggers. AB - BACKGROUND: Explosive synaptogenesis and synaptic pruning occur in the hippocampus during the first two weeks of postnatal life, coincident with a heightened susceptibility to seizures in rodents. To determine the temporal correlation between microglial development and age-dependent susceptibility and response to seizures, we quantified developmental changes in basal microglia levels and seizure-induced microglial activation in the hippocampus of Cx3Cr1(GFP /+) transgenic mice. METHODS: Basal levels of microglia were quantified in the hippocampi of Cx3Cr1(GFP /+) mice at P0, P5, P10, P15, P20, P25, P30, P40, and P60. Seizure susceptibility and seizure-induced microglial activation were assessed in response to febrile seizures (lipopolysaccharide followed by hyperthermia) and kainic acid-induced status epilepticus. RESULTS: The density of microglia within the hippocampus increased rapidly after birth, reaching a peak during the second week of life - the age at which the animals became most vulnerable to seizure triggers. In addition, this peak of microglial development and seizure vulnerability during the second postnatal week represented the time of maximal seizure-induced microglia activation. CONCLUSIONS: Overreactive innate immunity mediated by activated microglia may exacerbate acute injury to neuronal synapses and contribute to the long-term epileptogenic effects of early-life seizures. Anti-inflammatory therapy targeting excessive production of inflammatory mediators by activated microglia, therefore, may be an effective age specific therapeutic strategy to minimize neuronal dysfunction and prevent increases in susceptibility to subsequent seizures in developing animals. PMID- 26807336 TI - Neural correlates of different self domains. AB - INTRODUCTION: The neural substrates of states devoted to processing self-related information ("self-related states") remain not fully elucidated. Besides the complexity of the problem, there is evidence suggesting that self-related states vary according to the information domain being considered. Here, we investigated brain correlates for self-related states concerning historical aspects of one's life (autobiographical self), and one's ongoing body status (core self). We focused on memory-related regions, body-related regions, CMSs (cortical midline structures), and ICs (insular cortices). METHODS: This was a block-design fMRI study contrasting brain activity for core self (interoception and exteroception) and autobiographical self (personality traits and biographic facts) information domains. It involved 19 participants, who answered questions about each domain (four conditions). RESULTS: All conditions appeared to engage the regions of interest. Nonetheless, autobiographical self compared with core self showed greater activity in memory-related regions (e.g., hippocampus), MPFC (medial prefrontal cortex), superior PMC (posteromedial cortex), and anterior ICs. Core self compared with autobiographical self was associated with greater activity in body-related regions (e.g., somatosensory cortices, and EBA [extrastriate body area]), superior PMC, and posterior ICs. In addition, (1) facts compared with traits showed greater activity in body-related regions, memory-related regions, MPFC, and PMC; (2) traits compared with facts were associated with greater activity in the posterior part of the anterior cingulate cortex; (3) interoception compared with exteroception was associated with greater activity in body-related regions (e.g. postcentral gyrus), memory-related regions, MPFC, inferior PMC and ICs; (4) exteroception compared with interoception showed greater activity in some body-related regions (e.g., premotor cortices and EBA) and superior PMC. CONCLUSIONS: The results support the notion that the neural correlates of self-related states depend on the information domain. Those states seem distinguishable in terms of activity in memory-related and body-related regions, and activity in regions that have been associated with self processes (CMSs and the ICs). PMID- 26807337 TI - Attachment and maternal sensitivity are related to infants' monitoring of animated social interactions. AB - BACKGROUND: Infants have been shown to possess remarkable competencies in social understanding. Little is known, however, about the interplay between the quality of infants' social-emotional experiences with their caregivers and social cognitive processes in infancy. METHOD: Using eye-tracking we investigated the relation of infant attachment quality and maternal sensitivity with 12-month-old infants' monitoring patterns during the observation of abstractly depicted interactions of a "parent" and a "baby" figure. RESULTS: We found that secure infants focused their attention on the "parent" figure relative to the "baby" figure more than insecure infants when the two figures got separated. Infants with more sensitive mothers focused their attention more on the ongoing behavior of the "parent" figure after the separation than infants with less sensitive mothers when distress of the "baby" figure was implied by accompanying baby crying sounds. CONCLUSION: Our findings support the notion that early social emotional experiences with the caregiver are related to social information processing and that these social information processing patterns might be markers of infants' developing internal working models of attachment. PMID- 26807338 TI - Correlations between arm motor behavior and brain function following bilateral arm training after stroke: a systematic review. AB - BACKGROUND: Bilateral training (BT) of the upper limb (UL) might enhance recovery of arm function after stroke. To better understand the therapeutic potential of BT, this study aimed to determine the correlation between arm motor behavior and brain structure/function as a result of bilateral arm training poststroke. METHODS: A systematic review of quantitative studies of BT evaluating both UL motor behavior and neuroplasticity was conducted. Eleven electronic databases were searched. Two reviewers independently selected studies, extracted data and assessed methodological quality, using the Effective Public Health Practice Project (EPHPP) tool. RESULTS: Eight studies comprising 164 participants met the inclusion criteria. Only two studies rated "strong" on the EPHPP tool. Considerable heterogeneity of participants, BT modes, comparator interventions and measures contraindicated pooled outcome analysis. Modes of BT included: in phase and anti-phase; functional movements involving objects; and movements only. Movements were mechanically coupled, free, auditory-cued, or self-paced. The Fugl Meyer Assessment (UL section) was used in six of eight studies, however, different subsections were used by different studies. Neural correlates were measured using fMRI and TMS in three and five studies, respectively, using a wide variety of variables. Associations between changes in UL function and neural plasticity were inconsistent and only two studies reported a statistical correlation following BT. CONCLUSIONS: No clear pattern of association between UL motor and neural response to BT was apparent from this review, indicating that the neural correlates of motor behavior response to BT after stroke remain unknown. To understand the full therapeutic potential of BT and its different modes, further investigation is required. PMID- 26807339 TI - Neural basis of hierarchical visual form processing of Japanese Kanji characters. AB - INTRODUCTION: We investigated the neural processing of reading Japanese Kanji characters, which involves unique hierarchical visual processing, including the recognition of visual components specific to Kanji, such as "radicals." METHODS: We performed functional MRI to measure brain activity in response to hierarchical visual stimuli containing (1) real Kanji characters (complete structure with semantic information), (2) pseudo Kanji characters (subcomponents without complete character structure), (3) artificial characters (character fragments), and (4) checkerboard (simple photic stimuli). RESULTS: As we expected, the peaks of the activation in response to different stimulus types were aligned within the left occipitotemporal visual region along the posterior-anterior axis in order of the structural complexity of the stimuli, from fragments (3) to complete characters (1). Moreover, only the real Kanji characters produced functional connectivity between the left inferotemporal area and the language area (left inferior frontal triangularis), while pseudo Kanji characters induced connectivity between the left inferotemporal area and the bilateral cerebellum and left putamen. CONCLUSIONS: Visual processing of Japanese Kanji takes place in the left occipitotemporal cortex, with a clear hierarchy within the region such that the neural activation differentiates the elements in Kanji characters' fragments, subcomponents, and semantics, with different patterns of connectivity to remote regions among the elements. PMID- 26807340 TI - Rationale, design and methodology of the image analysis protocol for studies of patients with cerebral small vessel disease and mild stroke. AB - RATIONALE: Cerebral small vessel disease (SVD) is common in ageing and patients with dementia and stroke. Its manifestations on magnetic resonance imaging (MRI) include white matter hyperintensities, lacunes, microbleeds, perivascular spaces, small subcortical infarcts, and brain atrophy. Many studies focus only on one of these manifestations. A protocol for the differential assessment of all these features is, therefore, needed. AIMS: To identify ways of quantifying imaging markers in research of patients with SVD and operationalize the recommendations from the STandards for ReportIng Vascular changes on nEuroimaging guidelines. Here, we report the rationale, design, and methodology of a brain image analysis protocol based on our experience from observational longitudinal studies of patients with nondisabling stroke. DESIGN: The MRI analysis protocol is designed to provide quantitative and qualitative measures of disease evolution including: acute and old stroke lesions, lacunes, tissue loss due to stroke, perivascular spaces, microbleeds, macrohemorrhages, iron deposition in basal ganglia, substantia nigra and brain stem, brain atrophy, and white matter hyperintensities, with the latter separated into intense and less intense. Quantitative measures of tissue integrity such as diffusion fractional anisotropy, mean diffusivity, and the longitudinal relaxation time are assessed in regions of interest manually placed in anatomically and functionally relevant locations, and in others derived from feature extraction pipelines and tissue segmentation methods. Morphological changes that relate to cognitive deficits after stroke, analyzed through shape models of subcortical structures, complete the multiparametric image analysis protocol. OUTCOMES: Final outcomes include guidance for identifying ways to minimize bias and confounds in the assessment of SVD and stroke imaging biomarkers. It is intended that this information will inform the design of studies to examine the underlying pathophysiology of SVD and stroke, and to provide reliable, quantitative outcomes in trials of new therapies and preventative strategies. PMID- 26807341 TI - Prolonged fatigue in Ukraine and the United States: Prevalence and risk factors. AB - BACKGROUND: Prolonged, severe, unalleviated fatigue may be disabling whether it occurs on its own or in conjunction with medical or psychiatric conditions. This paper compares the prevalence and correlates of prolonged fatigue in general population samples in Ukraine versus the U.S. METHODS: Population surveys were conducted in 2002 in both Ukraine (Ukraine World Mental Health [WMH] Survey) and the U.S. (National Comorbidity Survey-Replication; NCS-R). Both surveys administered the Composite International Diagnostic Interview (CIDI 3.0), which contained modules assessing: neurasthenia (prolonged fatigue); mood, anxiety, and alcohol/drug use disorders; chronic medical conditions; and demographic characteristics. Multivariable logistic regression was used to examine risk factors in each country. RESULTS: The lifetime prevalence of prolonged fatigue was higher in Ukraine (5.2%) than the U.S. (3.7%). In both countries, one-fifth of individuals with prolonged fatigue had no medical or DSM-IV psychiatric condition. Also in both settings, fatigue was significantly associated with sociodemographic characteristics (being female, not working, and married before) as well as early onset and adult episodes of mood/anxiety disorder. Fatigue prevalence in Ukraine increased with age, but decreased in the U.S. at age 70. Unique risk factors for fatigue in Ukraine included lower socio-economic status, Ukrainian vs Russian ethnicity, and cardiovascular disease. Unique risk factors in the U.S. were parental depression/anxiety, adult episodes of alcohol/drugs, pain conditions, and other health problems. CONCLUSIONS: The lifetime prevalence of prolonged fatigue in Ukraine was 40% higher than that found in U.S. data. In addition, fatigue prevalence increased sharply with age in Ukraine perhaps due to limited social and medical resources and greater comorbidity. PMID- 26807342 TI - Anti-inflammatory therapies of amyotrophic lateral sclerosis guided by immune pathways. AB - Sporadic ALS patients display heterogeneous immune pathways in peripheral blood mononuclear cells (PBMCs). We tested nine sALS patients and one unaffected identical twin of an index case by RNA-Seq of PBMCs. The inflammatory patients (n = 3) clustered into a subset with an inflammatory Th1/Th17 signature and the non inflammatory patients (n = 7) into another subset with a B cell signature. The inflammatory subset was remarkable for granulocyte and agranulocyte diapedesis, hepatic fibrosis, roles of cytokines and metalloproteases. The non-inflammatory subset was highlighted by degradation of vitamin E, serotonin and nucleotides, altered T cell and B cell signaling, agranulocyte diapedesis, and up regulation of B cell genes. Identification of these differentially regulated pathways in sALS patients may guide the choice of anti-inflammatory therapies. PMID- 26807343 TI - Transcription factor Sp1 inhibition, memory, and cytokines in a mouse model of Alzheimer's disease. AB - Transcription factors are involved to varying extents in the health and survival of neurons in the brain and a better understanding of their roles with respect to the pathogenesis of Alzheimer's disease (AD) could lead to the development of additional treatment strategies. Sp1 is a transcription factor that responds to inflammatory signals occurring in the AD brain. It is known to regulate genes with demonstrated importance in AD, and we have previously found it upregulated in the AD brain and in brains of transgenic AD model mice. To better understand the role of Sp1 in AD, we tested whether we could affect memory function (measured with a battery of behavioral tests discriminating different aspects of cognitive function) in a transgenic model of AD by pharmaceutical modulation of Sp1. We found that inhibition of Sp1 function in transgenic AD model mice increased memory deficits, while there were no changes in sensorimotor or anxiety tests. Abeta42 and Abeta40 peptide levels were significantly higher in the treated mice, indicating that Sp1 elevation in AD could be a functionally protective response. Circulating levels of CXCL1 (KC) decreased following treatment with mithramycin, while a battery of other cytokines, including IL 1alpha, IL-6, INF-gamma and MCP-1, were unchanged. Gene expression levels for several genes important to neuronal health were determined by qRT-PCR, and none of these appeared to change at the transcriptional level. PMID- 26807344 TI - Erratum: Development, appraisal, validation and implementation of a consensus protocol for the assessment of cerebral amyloid angiopathy in post-mortem brain tissue. AB - In a collaboration involving 11 groups with research interests in cerebral amyloid angiopathy (CAA), we used a two-stage process to develop and in turn validate a new consensus protocol and scoring scheme for the assessment of CAA and associated vasculopathic abnormalities in post-mortem brain tissue. Stage one used an iterative Delphi-style survey to develop the consensus protocol. The resultant scoring scheme was tested on a series of digital images and paraffin sections that were circulated blind to a number of scorers. The scoring scheme and choice of staining methods were refined by open-forum discussion. The agreed protocol scored parenchymal and meningeal CAA on a 0-3 scale, capillary CAA as present/absent and vasculopathy on 0-2 scale, in the 4 cortical lobes that were scored separately. A further assessment involving three centres was then undertaken. Neuropathologists in three centres (Bristol, Oxford and Sheffield) independently scored sections from 75 cases (25 from each centre) and high inter rater reliability was demonstrated. Stage two used the results of the three centre assessment to validate the protocol by investigating previously described associations between APOE genotype (previously determined), and both CAA and vasculopathy. Association of capillary CAA with or without arteriolar CAA with APOE epsilon4 was confirmed. However APOE epsilon2 was also found to be a strong risk factor for the development of CAA, not only in AD but also in elderly non demented controls. Further validation of this protocol and scoring scheme is encouraged, to aid its wider adoption to facilitate collaborative and replication studies of CAA.[This corrects the article on p. 19 in vol. 3, PMID: 24754000.]. PMID- 26807345 TI - Acute Effects of Enhanced Eccentric and Concentric Resistance Exercise on Metabolism and Inflammation. AB - This study compared the metabolic, cardiopulmonary and inflammatory responses of novel acute machine based concentrically-focused resistance exercise (CON RX) and eccentrically-focused resistance exercise (ECC RX). Twenty healthy adults (26.8 +/- 5.9 yrs; 25.4 +/- 4.0 kg/m2) performed two work-matched RX exercise sessions. Cardiopulmonary responses, rating of perceived exertion (RPE), soreness, oxygen consumption; (VO2) were collected during each session. Blood lactate and levels of inflammatory cytokines interleukin-1 alpha (IL1alpha), interleukin-6 (IL6) and tumor necrosis factor-alpha (TNFalpha) were analyzed pre, post ad 24 hours post exercise. HR were higher (5-15bpm) during ECC RX (p<.05). Soreness ratings were consistently higher post-ECC RX compared to CON RX. VO2 area under the curve was higher during ECC than CON (31,905 ml/kg/min vs 25,864 ml/kg/min; p<.0001). Post ECC RX, TNFalpha levels increased compared to CON RX 23.2 +/- 23.9% versus 6.3 +/ 16.2% ( p=.021). ECC RX induced greater metabolic, cardiopulmonary and soreness responses compared to matched CON RX. This may be due to recruitment of additional stabilizer muscles and metabolic stress during the ECC RX. These factors should be considered when designing ECC RX programs particularly for untrained persons, older adults or those with history of cardiovascular disease. PMID- 26807349 TI - Does Activity Space Size Influence Physical Activity Levels of Adolescents? - A GPS study of an urban environment. AB - BACKGROUND: Physical activity (PA) is closely linked with child and youth health, and active travel may be a solution to enhancing PA levels. Activity spaces depict the geographic coverage of one's travel. Little is known about activity spaces and PA in adolescents. OBJECTIVE: To explore the relation between adolescent travel (using a spatial measure of activity space size) and daily moderate-to-vigorous PA (MVPA), with a focus on school days. METHODS: In Fall 2012, we used Global Positioning Systems to manually identify trips and generate activity spaces for each person-day; quantified by area for 39 students (13.8+/ 0.6 years, 38% female) attending high school in urban Downtown Vancouver, Canada. We assessed the association between activity space area and MVPA using multi level regression. We calculated total, school-day and trip-based MVPA for each valid person-day (accelerometry; >= 600 min wear time). RESULTS: On school days, students accrued 68.2 min/day (95% CI 60.4-76.0) of MVPA. Daily activity spaces averaged 2.2 km2 (95% CI 1.3-3.0). There was no association between activity space size and school-day MVPA. Students accrued 21.8 min/day (95% CI 19.2-24.4) of MVPA during school hours, 19.4 min/day (95% CI 15.1-23.7) during travel, and 28.3 min/day (95% CI 22.3-34.3) elsewhere. CONCLUSION: School and school travel are important sources of PA in Vancouver adolescents, irrespective of activity space area covered. PMID- 26807348 TI - Does Relative Age Affect Career Length in North American Professional Sports? AB - BACKGROUND: Relative age effects (RAEs) typically favour older members within a cohort; however, research suggests that younger players may experience some long term advantages, such as longer career length. The purposes of this study were to replicate previous findings on RAEs among National Hockey League (NHL) ice hockey players, National Basketball Association (NBA) basketball players and National Football League (NFL) football players and to investigate the influence of relative age on career length in all three sports. METHODS: Using official archives, birthdates and number of games played were collected for players drafted into the NBA (N = 407), NFL (N = 2380) and NHL (N = 1028) from 1980 to 1989. We investigated the possibility that younger players might be able to maximize their career length by operationalizing career length as players' number of games played throughout their careers. RESULTS: There was a clear RAE for the NHL, but effects were not significant for the NBA or NFL. Moreover, there was a significant difference in matches played between birth quartiles in the NHL favouring relatively younger players. There were no significant quartiles by career length effects in the NBA or NFL. CONCLUSIONS: The significant relationship between relative age and career length provides further support for relative age as an important constraint on expertise development in ice hockey but not basketball or football. Currently, the reason why relatively younger players have longer careers is not known. However, it may be worth exploring the influence of injury risk or the development of better playing skills. PMID- 26807347 TI - Sleep and Early Cortical Development. AB - Sleep is increasingly recognized as a key process in neurodevelopment. Animal data show that sleep is essential for the maturation of fundamental brain functions, and growing epidemiological findings indicate that children with early sleep disturbance suffer from later cognitive, attentional, and psychosocial problems. Still, major gaps exist in understanding processes underlying links between sleep and neurodevelopment. One challenge is to translate findings from animal research to humans. In this review, we describe parallels and differences in sleep and development of the cortex in humans and animals and discuss emerging questions. PMID- 26807350 TI - How to approach the pediatric flatfoot. AB - The most difficult aspect regarding treatment of the pediatric flatfoot is understanding who needs surgery, when it is necessary, and what procedure to be done. A thorough history, clinical examination, and imaging should be performed to guide the surgeon through an often complex treatment path. Surgical technique can be divided in three categories: Soft tissue, bony, and arthroereisis. This paper will describe the joint preserving techniques and their application to treat the pediatric flatfoot deformity. PMID- 26807351 TI - Football injuries of the ankle: A review of injury mechanisms, diagnosis and management. AB - Football is the most popular sport worldwide and is associated with a high injury rate, most of which are the result of trauma from player contact. Ankle injuries are among the most commonly diagnosed injuries in the game. The result is reduced physical activity and endurance levels, lost game time, and considerable medical cost. Sports medicine professionals must employ the correct diagnostic tools and effective treatments and rehabilitation protocols to minimize the impact of these injuries on the player. This review examines the diagnosis, treatment, and postoperative rehabilitation for common football injuries of the ankle based on the clinical evidence provided in the current literature. PMID- 26807352 TI - Mechanical and cellular processes driving cervical myelopathy. AB - Cervical myelopathy is a well-described clinical syndrome that may evolve from a combination of etiological mechanisms. It is traditionally classified by cervical spinal cord and/or nerve root compression which varies in severity and number of levels involved. The vast array of clinical manifestations of cervical myelopathy cannot fully be explained by the simple concept that a narrowed spinal canal causes compression of the cord, local tissue ischemia, injury and neurological impairment. Despite advances in surgical technology and treatment innovations, there are limited neuro-protective treatments for cervical myelopathy, which reflects an incomplete understanding of the pathophysiological processes involved in this disease. The aim of this review is to provide a comprehensive overview of the key pathophysiological processes at play in the development of cervical myelopathy. PMID- 26807353 TI - Role of negative pressure wound therapy in total hip and knee arthroplasty. AB - Negative-pressure wound therapy (NPWT) has been a successful modality of wound management which is in widespread use in several surgical fields. The main mechanisms of action thought to play a role in enhancing wound healing and preventing surgical site infection are macrodeformation and microdeformation of the wound bed, fluid removal, and stabilization of the wound environment. Due to the devastating consequences of infection in the setting of joint arthroplasty, there has been some interest in the use of NPWT following total hip arthroplasty and total knee arthroplasty. However, there is still a scarcity of data reporting on the use of NPWT within this field and most studies are limited by small sample sizes, high variability of clinical settings and end-points. There is little evidence to support the use of NPWT as an adjunctive treatment for surgical wound drainage, and for this reason surgical intervention should not be delayed when indicated. The prophylactic use of NPWT after arthroplasty in patients that are at high risk for postoperative wound drainage appears to have the strongest clinical evidence. Several clinical trials including single-use NPWT devices for this purpose are currently in progress and this may soon be incorporated in clinical guidelines as a mean to prevent periprosthetic joint infections. PMID- 26807354 TI - Direct anterior total hip arthroplasty: Literature review of variations in surgical technique. AB - The direct anterior approach to the hip has been suggested to have several advantages compared to previously popular approaches through its use of an intra muscular and intra-nervous interval between the tensor fasciae latae and sartorius muscles. Recent increased interest in tissue-sparing and minimally invasive arthroplasty has given rise to a sharp increase in the utilization of direct anterior total hip arthroplasty. A number of variations of the procedure have been described and several authors have published their experiences and feedback to successfully accomplishing this procedure. Additionally, improved understanding of relevant soft tissue constraints and anatomic variants has provided improved margin of safety for patients. The procedure may be performed using specially-designed instruments and a fracture table, however many authors have also described equally efficacious performance using a regular table and standard arthroplasty tools. The capacity to utilize fluoroscopy intra operatively for component positioning is a valuable asset to the approach and can be of particular benefit for surgeons gaining familiarity. Proper management of patient and limb positioning are vital to reducing risk of intra-operative complications. An understanding of its limitations and challenges are also critical to safe employment. This review summarizes the key features of the direct anterior approach for total hip arthroplasty as an aid to improving the understanding of this important and effective method for modern hip replacement surgeons. PMID- 26807356 TI - Review of management of unstable elbow fractures. AB - Stable and painless elbow motion is essential for activities of daily living. The elbow joint is the second most commonly dislocated joint in adults. The goals of treatment are to perform a stable fixation of all fractures, to achieve concentric and stable reduction of the elbow and to provide early motion. The treatment modality for complex elbow instability is almost always surgical. The treatment objectives are anatomic reduction, stable fixation, and early rehabilitation of the elbow. The common complications of these unstable fractures include recurrent instability, stiffness, myositis ossifications, heterotopic calcification, and neurovascular dysfunction. We analyzed the management of complex elbow fractures and instabilities on the basis of recent literature and suggested possible guidelines for the treatment in this paper. In conclusion, recognition of the injury pattern and restoration of the joint stability are the prerequisites for any successful treatment of an unstable elbow injury. PMID- 26807355 TI - Total elbow arthroplasty is moving forward: Review on past, present and future. AB - The elbow joint is a complex joint, which, when impaired in function, leads to severe disability. In some cases however, an arthroplasty might be an appropriate treatment. In the past four decades, large steps have been taken to optimize this treatment in order to achieve better post-operative outcomes. To understand these progresses and to discover aspects for upcoming improvements, we present a review on the past developments, the present state of affairs and future developments which may improve patient care further. PMID- 26807357 TI - Calcific tendinitis of the rotator cuff. AB - Calcific tendinitis within the rotator cuff tendon is a common shoulder disorder that should be differentiated from dystrophic calcification as the pathogenesis and natural history of both is totally different. Calcific tendinitis usually occurs in the fifth and sixth decades of life among sedentary workers. It is classified into formative and resorptive phases. The chronic formative phase results from transient hypoxia that is commonly associated with repeated microtrauma causing calcium deposition into the matrix vesicles within the chondrocytes forming bone foci that later coalesce. This phase may extend from 1 to 6 years, and is usually asymptomatic. The resorptive phase extends from 3 wk up to 6 mo with vascularization at the periphery of the calcium deposits causing macrophage and mononuclear giant cell infiltration, together with fibroblast formation leading to an aggressive inflammatory reaction with inflammatory cell accumulation, excessive edema and rise of the intra-tendineous pressure. This results in a severely painful shoulder. Radiological investigations confirm the diagnosis and suggest the phase of the condition and are used to follow its progression. Although routine conventional X-ray allows detection of the deposits, magnetic resonance imaging studies allow better evaluation of any coexisting pathology. Various methods of treatment have been suggested. The appropriate method should be individualized for each patient. Conservative treatment includes pain killers and physiotherapy, or "minimally invasive" techniques as needling or puncture and aspiration. It is almost always successful since the natural history of the condition ends with resorption of the deposits and complete relief of pain. Due to the intolerable pain of the acute and severely painful resorptive stage, the patient often demands any sort of operative intervention. In such case arthroscopic removal is the best option as complete removal of the deposits is unnecessary. PMID- 26807358 TI - Patient specific guides for total knee arthroplasty are ready for primetime. AB - AIM: To present the radiological results of total knee arthroplasty (TKA) with use of patient specific matched guides (PSG) from different manufacturer in patients suffering from severe osteoarthritis of the knee joint. METHODS: This study describes the results of 57 knees operated with 4 different PSG systems and a group operated with conventional instrumentation (n = 60) by a single surgeon. The PSG systems were compared with each other and subdivided into cut- and pin PSG. The biomechanical axis [hip-knee-ankle angle (HKA)], varus/valgus of the femur [frontal femoral component (FFC)] and tibia (frontal tibial component) component, flexion/extension of the femur [flexion/extension of the femur component (LFC)] and posterior slope of the tibia [lateral tibial component (LTC)] component were evaluated on long-leg standing and lateral X-rays. A percentage of > 3( degrees ) deviation was seen as an outlier. RESULTS: The inter class correlation coefficient (ICC) revealed that radiographic measurements between both assessors were reliable (ICC > 0.8). Fisher exact test was used to test differences of proportions. The percentage of outliers of the HKA-axis was comparable between both the PSG and conventional groups (12.28% vs 18.33%, P < 0.424) and the cut- and pin PSG groups (14.3% vs 10.3%, P < 1.00). The percentage of outliers of the FFC (0% vs 18.33%, P < 0.000), LFC (15.78% vs 58.33%, P < 0.000) and LTC (15.78% vs 41.67%, P < 0.033) were significant different in favour of the PSG group. There were no significant differences regarding the outliers between the individual PSG systems and the PSG group subdivided into cut- and pin PSG. CONCLUSION: PSG for TKA show significant less outliers compared to the conventional technique. These single surgeon results suggest that PSG are ready for primetime. PMID- 26807359 TI - Surgical treatment of sacral fractures following lumbosacral arthrodesis: Case report and literature review. AB - Sacral fractures following posterior lumbosacral fusion are an uncommon complication. Only a few case series and case reports have been published so far. This article presents a case of totally displaced sacral fracture following posterior L4-S1 fusion in a 65-year-old patient with a 15-year history of corticosteroid use who underwent open reduction and internal fixation using iliac screws. The patient was followed for 2 years. A thorough review of the literature was conducted using the Medline database between 1994 and 2014. Immediately after the revision surgery, the patient's pain in the buttock and left leg resolved significantly. The patient was followed for 2 years. The weakness in the left lower extremity improved gradually from 3/5 to 5/5. In conclusion, the incidence of postoperative sacral fractures could have been underestimated, because most of these fractures are not visible on a plain radiograph. Computed tomography has been proved to be able to detect most such fractures and should probably be performed routinely when patients complain of renewed buttock pain within 3 mo after lumbosacral fusion. The majority of the patients responded well to conservative treatments, and extending the fusion construct to the iliac wings using iliac screws may be needed when there is concurrent fracture displacement, sagittal imbalance, neurologic symptoms, or painful nonunion. PMID- 26807360 TI - Liver fat content is negatively associated with atherosclerotic carotid plaque in type 2 diabetic patients. AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is independently associated with atherosclerosis in nondiabetic individuals. In type 2 diabetic patients, the link between fatty liver and atherosclerosis is less clear. Here, we assessed whether liver fat content evaluated using (1)H-magnetic resonance spectroscopy ((1)H-MRS) was independently associated with prevalent carotid plaque as a marker of atherosclerosis in type 2 diabetic patients. METHODS: One hundred and forty four prospectively enrolled patients with type 2 diabetes underwent liver fat content measurement using (1)H-MRS and carotid plaque assessment using ultrasound. Multiple logistic regressions were used to identify factors associated with carotid plaque. RESULTS: Mean +/- SD liver fat content was 9.86+/ 8.12%. Carotid plaque prevalence was 52.1% (75/144). Patients without plaque were younger (P=0.006) and had a smaller visceral fat area (P=0.015), lower reported prevalence of previous cardiovascular events or current statin therapy (P=0.002), and higher liver fat content than those with plaque (P=0.009). By multivariable logistic regression, increased liver fat content independently predicted the absence of carotid plaque [odds ratios (ORs), 0.94; 95% confidence intervals (CIs), 0.89-0.99; P=0.017]. CONCLUSIONS: Liver fat content measured by (1)H-MRS is higher in type 2 diabetic patients without carotid plaque compared to those with plaque. This study suggests that increased liver fat content could be associated with a relative protection against carotid atherosclerosis in patients with type 2 diabetes mellitus. PMID- 26807361 TI - Optimization and comparison of two practical dual-tuned birdcage configurations for quantitative assessment of articular cartilage with sodium magnetic resonance imaging. AB - BACKGROUND: In this study, two practical dual-tuned birdcage configurations for quantitative assessment of articular cartilage with sodium magnetic resonance imaging (MRI) were designed and compared. METHODS: Two 1.5 T dual-tuned birdcages, a four-ring birdcage (FRB) and an alternating rungs birdcage (ARB), were built and then characterized by bench and MRI measurements. The relative uniformity (RU) and the efficiency of the coils were compared using (23)Na and (1)H B1 maps. In vivo images of a volunteer were acquired. RESULTS: Bench measurements showed matching and decoupling coefficients of the quadrature channels lower than -20 dB. The RUs and 180 degrees pulse amplitudes of the FRB/ARB were determined as: (1)H RU =94.4/74.4%, (23)Na RU =95.2/93.6%, (1)H 180 degrees pulse amplitude =69.2/75.4 V and (23)Na 180 degrees pulse amplitude =45.1/45.9 V. The in vivo (23)Na images acquired with the FRB show a signal-to noise ratio (SNR) of 6 to 14 in the cartilage. CONCLUSIONS: Due to its superior (1)H homogeneity and efficiency and its slightly better (23)Na homogeneity, the FRB is the overall preferred coil for the given requirements of this study. The achieved in vivo SNR is adequate for quantitative (23)Na and high resolution (1)H imaging. PMID- 26807362 TI - Comparison of three different embolic materials for varicocele embolization: retrospective study of tolerance, radiation and recurrence rate. AB - BACKGROUND: To evaluate pain, radiation and recurrence rates in patients undergoing varicocele embolization with three different embolic materials. METHODS: Retrospective study of 182 consecutive patients who underwent transcatheter retrograde varicocele embolization from July 2011 to May 2015 with glue (Glubran((r))2) (group 1, n=63), mechanical agents (coils and/or plugs) (group 2, n=53) or a sclerosing agent (polidocanol) (group 3, n=66). Patients were asked by telephone interview to evaluate pain during embolization and at 1, 7 and 30 days using a quantitative pain scale ranging from 0 to 10. Duration of scopy, kinetic energy released per unit mass (kerma) and dose area product (DAP) were assessed as radiation parameters during embolization procedures. Recurrence rates after treatment were also evaluated. Statistical analyses were performed using parametric and non-parametric tests. RESULTS: Patients in the three study groups were comparable for age, clinical indication and embolization side. No difference was noted for significant pain (pain score >=3) during embolization and at 1, 7 and 30 days after treatment. Discomfort (pain score <3) was more frequent in group 1 than in groups 2 and 3 at 7 days after the procedure (P=0.049). No difference in discomfort was noted during embolization or at 1 and 30 days. Duration of scopy was shorter (P<0.0001) and kerma was lower (P=0.0087) in group 1 than in groups 2 and 3. DAP was lower in group 1 than in group 2 (P=0.04) but no difference was noted between groups 1 and 3, and groups 2 and 3. The recurrence rate at a mean follow-up of 24.4 months (range, 2-53 months) was significantly lower in group 1 than in the two other groups (P=0.032). CONCLUSIONS: The use of Glubran((r))2 acrylic glue for varicocele embolization is safe and leads to less radiation and lower recurrence rates than is the case for other embolic materials without any more significant pain. PMID- 26807363 TI - Changes in mitral annular morphology and function in young patients with type 1 diabetes mellitus-results from the three-dimensional speckle tracking echocardiographic MAGYAR-Path Study. AB - BACKGROUND: Alterations in mitral annular size and function could be demonstrated in cardiomyopathies and ischaemic heart disease. The present study was designed to evaluate mitral annulus (MA) morphology and function in young type 1 diabetes mellitus (T1DM) patients by three-dimensional speckle tracking echocardiography (3DSTE) and to compare their results to matched healthy controls. METHODS: The study comprised 18 patients with T1DM (mean age: 33.0+/-8.0 years). Their results were compared to that of 20 age- and gender-matched healthy controls (mean age: 37.8+/-10.9 years). Complete two-dimensional (2D) Doppler echocardiography and 3DSTE have been performed in all cases. RESULTS: No significant differences could be demonstrated in demographic and standard echocardiographic parameters between the groups. Significantly enlarged diastolic MA diameter (2.87+/-0.27 mm vs. 2.58+/-0.32 mm, P=0.01), MA diameter index 1.61+/-0.20 cm/m(2) vs. 1.30+/-0.39 cm/m(2), P=0.008, and MA area index (4.81+/-0.88 cm(2)/m(2) vs. 3.91+/-1.35 cm(2)/m(2), P=0.03) could be demonstrated in T1DM together with augmented MA fractional shortening (28.64+/-9.63% vs. 20.35+/-12.50%, P=0.05). CONCLUSIONS: Early alterations in MA size and function could be demonstrated in young patients with T1DM by 3DSTE. PMID- 26807364 TI - Impact of obesity and acquisition protocol on (123)I-metaiodobenzylguanidine indexes of cardiac sympathetic innervation. AB - BACKGROUND: This study was designed to assess the impact of obesity and acquisition protocol on (123)I-metaiodobenzylguanidine (MIBG) indexes of cardiac sympathetic innervation. METHODS: Forty-five patients with heart failure (HF) (38 men, age 58+/-15 years) underwent (123)I-MIBG cardiac imaging. Of these patients, 10 were obese [body mass index (BMI) >=30 kg/m(2)]. Ten-minute planar images of the thorax in anterior view were performed 15 minutes ("early" image) and 3 hours and 50 minutes ("late" image) after tracer administration in both supine- and prone-position. Early and late (123)I-MIBG heart-to-mediastinum (H/M) ratios and washout rate were computed. RESULTS: In overall study population, early and late (123)I-MIBG H/M ratios and washout rate were comparable between supine- and prone position acquisitions. Obese patients had a lower early and late (123)I-MIBG H/M ratios both in supine (P<0.01) and prone (P<0.05) positions compared to non-obese subjects. CONCLUSIONS: Our results indicate that in HF patients, obesity has a significant impact on (123)I-MIBG indexes of cardiac sympathetic innervation. Prone-position did not change early and late (123)I-MIBG H/M ratios and washout rate compared to supine position both in obese and non-obese HF patients. PMID- 26807365 TI - Antral gastritis caused by Helicobacter pylori infection in the pediatric age group is associated with increased mesenteric lymph node dimension observed by ultrasonography. AB - BACKGROUND: To find out if transabdominal ultrasonography (US) may have a predictive role for detection of antral gastritis and Helicobacter pylori (HP) infection in the antrum of pediatric age group. METHODS: A total of 91 (63.6%) patients and 52 (36.4%) controls were allocated into two groups as follows: Group 1 (n=91): patients with complaints and endoscopic findings consistent with gastritis and documented HP infection; Group 2 (n=52): patients with complaints and endoscopic findings consistent with gastritis in the absence of documented HP infection. These two groups were compared in terms of demographics and biggest mesenteric lymph node detected, muscularis mucosa thickness, submucosal thickness, muscularis propria thickness, and total gastric wall thickness. RESULTS: The two groups exhibited no statistically significant difference with respect to age (P=0.747), and presenting symptoms (P=0.982). However, the mesenteric lymph node dimension was significantly increased in Group 1 (P=0.039). Median mesenteric lymph node dimension was 12.9 (+/-15.4) mm in Group 1, while 11.0 (+/-12.8) mm in Group 2. No significant difference was observed between groups in terms of muscularis mucosa thickness (P=0.243), submucosal thickness (P=0.174), muscularis propria thickness (P=0.356), and total gastric wall thickness (P=0.223). CONCLUSIONS: Antral gastritis caused by HP infection in the pediatric age group is associated with increased mesenteric lymph node dimension observed by US. PMID- 26807366 TI - Mean apparent diffusion coefficient values in defining radiotherapy planning target volumes in glioblastoma. AB - BACKGROUND: To evaluate mean apparent diffusion coefficient (ADC) values on pre radiotherapy magnetic resonance (MR) at sites that gave rise to glioblastoma (GBM) recurrence compared to similar surrounding background tissue that did not progress to tumor. METHODS: Twenty out of 110 consecutive patients with pathology proven GBM treated at our institution from 1/1/2009 to 5/31/2012 had definitive recurrence 6 months following radiotherapy. In this single-center retrospective cohort study, pre- and post-radiotherapy MR brain exams were evaluated. Sites of tumor recurrence on post-therapy exams were co-localized to pre-therapy exams and the background tissue type which gave rise to tumor was noted (i.e., T2 hyperintensity, normal appearing white or gray matter). Similar surrounding background tissue not progressing to tumor was also selected. Two radiologists compared mean ADC values on pre-radiotherapy MR for sites which gave rise to future tumor recurrence and sites of similar background tissue. RESULTS: Pre radiotherapy mean ADC values were significantly lower in regions of future tumor recurrence than in regions of surrounding background tissue not progressing to tumor (P=0.003). There were no significant quantitative differences on T1 weighted pre contrast (P=0.50) or T2-weighted (P=0.10) sequences between sites. There was strong interobserver agreement with an intraclass correlation of 0.867 for ADC values at sites of future tumor recurrence and background tissue. CONCLUSIONS: Mean ADC values may help predict sites of future gross tumor recurrence in GBM, which could be helpful in radiation therapy planning. PMID- 26807367 TI - Are there any novel radiological diagnostic clues in magnetic resonance imaging for vertebrobasilar insufficiency? AB - BACKGROUND: The aim of the current study was to investigate whether signal intensities on magnetic resonance imaging (MRI) views and radiological findings on Doppler ultrasonography may have a diagnostic value for vertebrobasilar insufficiency (VBI). METHODS: This case-control study was performed on demographic and radiologic data derived from 18 VBI patients and 58 healthy controls in the radiology department of a tertiary care center. The blood flow characteristics including peak systolic and end diastolic flow rates, resistance and pulsatility indices, mean velocities, flow rates, diameters and intensity pattern of vertebral arteries on cervical and cranial MRI sequences were noted. The association between blood flow characteristics and signal patterns on MRI views was investigated in VBI patients and controls. RESULTS: Blood flow and vessel diameter were significantly decreased in VBI patients compared to controls on both sides (P<0.001). In contrast, other parameters did not exhibit any remarkable difference between VBI and control groups. The distribution of hypo- or hyperintense signals in VBI and control groups was similar. No remarkable variabilities were detected in blood flow characteristics of cases presenting with signals having different intensities on MRI sequences. CONCLUSIONS: In conclusion, results of the current study have demonstrated that assessment of blood flow and vascular diameter may be important for ruling in VBI. Nevertheless, the intensity of signals derived from vessels seems not reveal any data of diagnostic significance in these cases. Further studies on larger populations may allow development and exploration of newer diagnostic techniques and clues for VBI. PMID- 26807368 TI - Different patterns of left ventricular rotational mechanics in cardiac amyloidosis-results from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study. AB - Cardiac amyloidosis (CA) is an infiltrative disease primarily caused by extracellular tissue deposition of amyloid fibrils in the myocardial interstitium. The aim of the present study was to examine left ventricular (LV) rotational mechanics in biopsy-proven CA by three-dimensional (3D) speckle tracking echocardiography (STE). Ten patients (65.3+/-11.5 years, 6 males) with CA entered the study. The mean basal LV rotations were 0.3+/-3.8 degrees , while mean apical LV rotations proved to be 7.0+/-3.3 degrees . LV basal and apical rotations were in the same counterclockwise direction in 6 out of 10 CA patients demonstrating near absence of LV twist [LV rigid body rotation (RBR)]. Apico basal difference was near 3 or less degrees in three patients with LV-RBR, and 6 10 degrees in the other three subjects with LV-RBR. One another patient showed normal rotational mechanics, while two patients had significant hyporotations and one had significant hyperrotations in normal directions. To conclude with, different patterns of LV rotational mechanics could be demonstrated in CA. LV RBR, the near absence of LV twist seems to be a frequent phenomenon in CA. PMID- 26807370 TI - Vascular anomalies of the head and neck in children. AB - Sixty percent of vascular anomalies in children are found in the head and neck. These lesions can present throughout antenatal, perinatal and childhood development. They broadly fall into two categories: vascular tumours and vascular malformations. Their clinical and, often, psychological impact is determined by both pathological type and location: many lesions follow an uncomplicated natural course and other more complex, extensive or progressive lesions can present a threat to life from mass effect, haemorrhage or large volume arteriovenous shunting. Vascular tumours include infantile haemangioma (IH), congenital haemangioma (CH) and kaposiform hemangioendothelioma (KH); of which IH is the most common. Management options for vascular tumours include conservative approaches, oral medications and surgical intervention as determined by tumour type, location and associated complications. Vascular malformations can be categorised into low flow and high flow lesions. Low flow lesions include capillary, venous and lymphatic malformations (LMs). High flow lesions describe the arteriovenous malformations (AVMs), a highly heterogeneous group of lesions which can present in a variety of ways-the mainstay of treatment for these dynamic lesions is endovascular or surgical obliteration. We provide a practical framework for clinical classification of vascular anomalies of the head and neck in children. We also explore principles of their clinical and radiological assessment along with management, highlighting the importance of a multi disciplinary approach. PMID- 26807371 TI - Keratoameloblastoma or Kerato-odontoameloblastoma: report of its soft tissue recurrence with literature review. AB - Keratoameloblastoma (KA) is a rare histological variant of the ameloblastoma with extensive keratin production within the odontogenic islands as well as in the fibrous stroma. Pindborg first reported it in 1970, since then only 18 cases have been reported in the literature. We report a soft tissue recurrence of KA, involving right posterior region of the lower jaw in a 27-year-old female. PMID- 26807369 TI - T1rho magnetic resonance: basic physics principles and applications in knee and intervertebral disc imaging. AB - T1rho relaxation time provides a new contrast mechanism that differs from T1- and T2-weighted contrast, and is useful to study low-frequency motional processes and chemical exchange in biological tissues. T1rho imaging can be performed in the forms of T1rho-weighted image, T1rho mapping and T1rho dispersion. T1rho imaging, particularly at low spin-lock frequency, is sensitive to B0 and B1 inhomogeneity. Various composite spin-lock pulses have been proposed to alleviate the influence of field inhomogeneity so as to reduce the banding-like spin-lock artifacts. T1rho imaging could be specific absorption rate (SAR) intensive and time consuming. Efforts to address these issues and speed-up data acquisition are being explored to facilitate wider clinical applications. This paper reviews the T1rho imaging's basic physic principles, as well as its application for cartilage imaging and intervertebral disc imaging. Compared to more established T2 relaxation time, it has been shown that T1rho provides more sensitive detection of proteoglycan (PG) loss at early stages of cartilage degeneration. T1rho has also been shown to provide more sensitive evaluation of annulus fibrosis (AF) degeneration of the discs. PMID- 26807372 TI - Late postpartum eclampsia complicated with posterior reversible encephalopathy syndrome: a case report and a literature review. AB - Posterior reversible encephalopathy syndrome (PRES) is a rare but serious clinical-neuroradiological entity characterized by headache, vomiting, visual disturbances, altered mental status, seizures, and unconsciousness associated with the characteristic imaging findings including sub-cortical vasogenic edema at the bilateral parietal and occipital lobes. We describe a case of 28-year-old PRES patient secondary to delayed maternal postpartum eclampsia. This patient was not initially diagnosed with pre-eclampsia and PRES. The diagnosis was established after magnetic resonance imaging. After treatment this patient's PRES resolved. Early diagnosis and treatment are the keys to reverse PRES. A literature review for PRES is provided in this report. PMID- 26807373 TI - AME survey-003 A1-part 2: the motivation factors of medical doctors in China. AB - BACKGROUND: The professional moral and job satisfaction of medical profession remain highly disputed in media in China. On the other hand, there is wide disaffection of patients toward doctors in China. This survey aims to obtain a better understanding of the motivation of Chinese medical professionals. METHODS: An anonymous online cross-sectional survey, AME survey III, was conducted using the platform provided by DXY (www.dxy.cn) during the period of September 10-23, 2015. In total 2,356 DXY users completed the survey, including 1,740 males and 617 females, with a mean age of 31.96+/-7.03 yrs. RESULTS: The reasons (multiple choices) for career disaffection included poor patient/doctor relationship (88.6%), imbalance between workload and pay (79.5%), could not enter the preferred specialty (14.14%), and working in small clinics with no career progress (11.17%). If given the choice to enter the specialty as well as the hospital grade of their choice, 73.8% dissatisfied respondents replied they would like to be a doctor. For the dis-satisfied respondents, university teacher appeared to be the most popular career choice. The cited high workload was considered to be due to (I) imbalance in geographical allocation of doctors and insufficient training of doctors; (II) many red-tapism formalities; (III) Chinese patients often have unreasonable requests; (IV) over-examination and over treatment; (V) high pressure to publish papers. One hundred and twelve respondents have their child/children attending university or graduated from university, 25.0% of them are pursuing a career in medicine. Nine hundred and ninety respondents have child/children while did not reach university age yet, among them 23.62% would like their child/children to study medicine. 64.87% of the 2,356 participants favor China to open up medical market to qualified foreign medical organizations to take part in fair competition, and 57.91% favor the government supporting regulated private hospitals. CONCLUSIONS: The moral and motivation of medical doctors in China are likely to be similar to other continuously evolving societies. Cost-effective use of existing resources should be explored as the first priority. PMID- 26807374 TI - Spontaneous spinal epidural haematoma mimicking acute coronary syndrome. AB - Spontaneous spinal epidural hematoma (SSEH) is an acute neurological emergency which carries significant morbidity unless diagnosed and treated in a timely fashion. Some cases of SSEH are idiopathic but there is a well-recognised association with deranged coagulation and abnormalities of clotting. In recent years there has been increasing availability of novel anti-platelet agents, often prescribed in the setting of suspected acute coronary syndromes (ACS) and following percutaneous coronary interventions and these agents also present an increased risk of SSEH. We present a case of SSEH following an acute presentation with chest pain and treatment with dual anti-platelet therapy. PMID- 26807375 TI - Bilateral reversible basal ganglia changes associated with dystonia and hemifacial spasms in central nervous system lupus. AB - We report a 40-year-old woman with systemic lupus erythematosus (SLE) and associated inflammatory polyarthritis who presented with acute facial dystonic spasms. Her speech was also affected. An MRI brain showed bilateral symmetrical basal ganglia signal change on T2. This movement disorder was due to an acute manifestation of her lupus. Her symptoms resolved rapidly following treatment with (oral) steroids. Repeat MRI brain at 1 month showed complete resolution of the basal ganglia signal change. This is the first time that facial spasms and dystonia with corresponding MRI changes are reported as a presentation of lupus affecting the central nervous system (CNS lupus). PMID- 26807376 TI - Traumatic right diaphragmatic rupture with hepatothorax: a diagnostic challenge! PMID- 26807377 TI - Axonotmesis of the femoral and sciatic nerves mimicking lumbar radiculopathy. PMID- 26807378 TI - Acute Hepatic Phenotype of Wilson Disease: Clinical Features of Acute Episodes and Chronic Lesions Remaining in Survivors. AB - BACKGROUND AND AIMS: Wilson disease (WD) is an inherited disorder of copper metabolism, and an international group for the study of WD (IGSW) has proposed three phenotypes for its initial presentation: acute hepatic, chronic hepatic, and neurologic phenotypes. Characterization of the acute hepatic phenotype may improve our understanding of the disease. METHODS: Clinical features of 10 WD patients with the acute hepatic phenotype and characteristics of chronic lesions remaining in survivors were assessed by the European Association for the Study of the Liver (EASL) guidelines. RESULTS: All six patients younger than 30 years had survived an acute episode of hemolytic anemia with residual liver disease of cirrhosis or chronic hepatitis. The acute episode was self-limiting in two of the four patients over the age of 30 years and progressed to acute liver failure in the other two patients. One of the two survivors had residual liver disease of chronic hepatitis, while the other had chronic hepatitis and neurologic disease. Neurologic disease remained in a patient who successfully received a liver transplantation. During acute episodes, serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) changed rapidly along with anemia. Liver-specific ALT levels were age-dependently correlated with hemoglobin (Hb) concentrations. Enzyme reduction was milder for AST than ALT, which resulted in a high AST/ALT ratio in the anemic stage. The anemic stage in two patients transformed to acute liver failure. CONCLUSIONS: All survivors of an acute episode of the acute hepatic phenotype had residual liver disease or both liver and neurologic diseases. The rapid changes in liver enzymes during the acute episode and the liver and neurologic diseases remaining in survivors may provide a better understanding of WD. PMID- 26807379 TI - Identification of Nonalcoholic Fatty Liver Disease following Pancreatic Surgery in a Western Cohort Using a Novel Radiographic Technique. AB - BACKGROUND AND AIMS: While traditional risk factors for the development of nonalcoholic fatty liver disease (NAFLD) relate to metabolic syndrome, several Asian studies have suggested a high rate of de novo NAFLD following pancreaticoduodenectomy (PD). The aim of this study is to identify de novo NAFLD after pancreatic surgery and its associated risk factors. METHODS: A retrospective cohort of patients at a single center that underwent PD or distal pancreatectomy (DP) over 7 years was identified. Pre- and postoperative contrast enhanced computed tomography scans of the abdomen were reviewed, including attenuation measurements of the liver, spleen, and muscle. Primary outcomes included hepatic attenuation, liver to muscle ratio (LMR), and liver to spleen ratio (LSR). RESULTS: Of the 96 patients (mean age 64.3) included, 70% underwent PD, and 30% underwent DP. The mean LMR decreased significantly from 1.81 to 1.66 (p=0.02), noted only in men. No interaction effect with LMR was observed with surgical type, chemotherapy, blood loss, pancreatic enzyme replacement, or transaminases. LMR decreased in 55% of subjects. CONCLUSIONS: Increased fatty infiltration, as evidence by decreased LMR, was found among men that underwent PD and DP within a year of surgery. This may be related to weight loss and malabsorption and deserves further investigation. PMID- 26807380 TI - Patients with Gastric Antral Vascular Ectasia (GAVE) Are at a Higher Risk of Gastrointestinal Bleeding in the Absence of Cirrhosis. AB - BACKGROUND AND AIMS: Gastric antral vascular ectasia (GAVE) is commonly found in patients with cirrhosis, but it is also associated with other diseases in the absence of cirrhosis. Whether GAVE confers a different severity of gastrointestinal (GI) bleeding between patients with and without cirrhosis remains unknown. We aim to examine whether there is a difference in clinically significant GI bleeding due to GAVE in patients with or without cirrhosis. METHODS: This is a retrospective case-control study of patients who were diagnosed with GAVE between January 2000 and June 2014. Patients were categorized into cirrhosis and noncirrhosis groups, and those with an additional GI bleeding source were excluded. Univariate comparisons and multivariable models were constructed using logistic regression. RESULTS: In total, 110 patients diagnosed with GAVE on esophagogastroduodenoscopy (EGD) were included in our analysis; 84 patients had cirrhosis (76.4%) and 26 (23.6%) did not. Active GI bleeding was more prevalent in patients without cirrhosis (63.4% vs. 32.1%, p=0.003) despite similar indications for EGD, and endoscopic treatment with argon plasma coagulation (APC) was required more often in this group, approaching statistical significance (27% vs. 10.7%, p=0.056). There was no difference in bleeding severity, as evidenced by similar re-bleeding rates, surgery, or death attributed to uncontrolled bleeding. The strongest independent risk factor for GI bleeding was the absence of cirrhosis (odds ratio (OR): 5.151 (95% confidence interval (CI): 1.08-24.48, p=0.039). CONCLUSIONS: Patients with GAVE in the absence of cirrhosis are at higher risk for active GI bleeding and require more frequent endoscopic treatment than similar patients with cirrhosis. It may be worthwhile to treat GAVE in this population even in the absence of active bleeding. PMID- 26807381 TI - Hepatocellular Carcinoma Related to Schistosoma mansoni Infection: Case Series and Literature Review. AB - BACKGROUND AND AIMS: Schistosomiasis is a major chronic disease of humans in endemic regions, and infected individuals may develop a spectrum of pathology, including hepatic fibrosis, hepatosplenomegaly, and portal hypertension. Hepatocellular carcinoma (HCC) is considered the fifth most common cancer in the world, and there is limited and controversial evidence suggesting that Schistosoma mansoni infection may be a possible risk factor for HCC. The aim of this study was to report a case series of patients with HCC and S. mansoni infection and to conduct a literature review on the topic. METHODS: From January 2002 to January 2015, an institutional database was screened retrospectively to identify patients with HCC and S. mansoni infection at a single center in the Department of Gastroenterology of University of Sao Paulo School of Medicine and Hospital das Clinicas, Brazil. RESULTS: Seven cases were included. The mean age of patients was 62.1+/-10.3 years; six (85.7%) were male and one (14.3%) was female. All cases had positive epidemiology, coming from endemic areas of S. mansoni infection in Brazil, and four (57.1%) had previous complications (upper gastrointestinal bleeding) related to portal hypertension or surgery intervention (splenectomy) performed more than 10 years before the HCC diagnosis. Nontumoral portal vein thrombosis was identified in five (71.4%) patients. All patients had negative serology for HCV, and four (57.1%) had positivity of HBVcore antibodies without evidence of viral replication. According to BCLC staging, one (14.3%) patient was BCLC A and received TACE instead of RFA because HCC size was >30 mm; three (42.8%) BCLC B patients received sorafenib instead of local regional treatment due to the presence of nontumoral TPV. During follow-up, all patients developed tumoral progression and died. CONCLUSIONS: It remains unclear if S. mansoni infection alone has carcinogenic potential. The available literature indicates that S. Mansoni, in the presence of HBV and HCV infections, likely acts as a cofactor for the hepatic lesion and potentiates injury. PMID- 26807382 TI - TM6SF2 E167K Variant, a Novel Genetic Susceptibility Variant, Contributing to Nonalcoholic Fatty Liver Disease. AB - Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of liver dysfunction worldwide, and its prevalence is highly associated with genetic susceptibility. The transmembrane 6 superfamily member 2 (TM6SF2) E167K variant represents a general genetic determinant of hepatic triglyceride content and lobular inflammation, and its presence appears to be directly involved in the pathogenesis and development of NAFLD. Although this variant appears to be a novel powerful modifier in the development of NAFLD, whether it is associated with an increased risk of NAFLD-related liver fibrosis and hepatocellular carcinoma (HCC) remains to be determined. The aim of this review is to describe the functions of the TM6SF2 E167K variant and its association with NAFLD, with particular emphasis on the underlying mechanisms of its role in the development and progression of NAFLD. Additionally, the links between the TM6SF2 E167K variant and NAFLD-related liver fibrosis and HCC will be discussed. PMID- 26807383 TI - IL-6 Plays a Crucial Role in HBV Infection. AB - Interleukin-6 (IL-6), a cytokine mainly produced by activated monocytes, has broad pleiotropic actions that affect the functions of a variety of lymphoid cells. The roles of IL-6 in regulating immunity to infections are currently being defined. Remarkably, IL-6-mediated cellular and humoral immune responses play a crucial role in determining the outcome of viral infection. This article reviews the current knowledge on the critical role of IL-6 in hepatitis B virus (HBV) infection. As a competent intermediary, IL-6 derived from activated monocytes plays an important role in promoting lymphocytes responses that are essential for effective viral control. However, as a mediator of inflammation, IL-6 is also involved in the development of HBV-induced liver cirrhosis and exacerbating liver injury. Overall, the current data point to IL-6 as an immunoregulatory cytokine in HBV infection. Immunotherapeutic strategies aimed at optimizing the beneficial effects of IL-6 in HBV infection may prove to be an ordeal in the future, as they should foster the strengths of IL-6 while circumventing potential drawbacks. PMID- 26807385 TI - De novo Hepatocellular Carcinoma after Liver Transplantation. AB - Liver transplantation is the definitive therapy for patients with advanced liver disease and its complications. Patients who are transplanted with a diagnosis of hepatocellular carcinoma (HCC) are at risk of recurrent cancer, and these patients are monitored on a regular basis for recurrence. In contrast, de novo HCC following liver transplantation is a very rare complication, and recipients without HCC at the time of transplantation are not screened. We describe the clinical features of de novo HCC over a decade after achieving a sustained viral response with treatment of hepatitis C and two decades after liver transplantation. Our case highlights the necessity of screening for HCC in the post-transplant patient with advanced liver disease even after viral clearance. PMID- 26807386 TI - Hepatitis E: An Underdiagnosed, Emerging Infection in Nonendemic Regions. AB - Although hepatitis E virus (HEV) is the primary cause of enterically transmitted acute hepatitis and jaundice in developing countries, locally acquired HEV infections are increasing in nonendemic countries. As such, HEV is emerging as an underdiagnosed cause of infection. This report describes three clinically variable cases of HEV infection with unusual clinical presentations. These cases highlight the fact that HEV should be considered in the differential diagnosis of patients with unexplained hepatitis (acute or chronic) with or without extrahepatic manifestations. HEV should also be considered in patients with persistently elevated liver enzymes who have not travelled to known HEV-endemic regions. Lack of knowledge among physicians and an absence of standardized diagnostic tests may result in increased morbidity and mortality from HEV infection. PMID- 26807384 TI - The Role of Immune Cells in Chronic HBV Infection. AB - Hepatitis B virus (HBV) infection is a major cause of chronic liver diseases that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses are important factors that determine whether HBV infection is cleared or persists. After infection, viral replication occurs inside hepatocytes, and the secretion of infectious virions can take place at high rates for decades. Consequently, HBV DNA and viral proteins, like HBV early antigen (HBeAg) and HBV surface antigen (HBsAg), can be easily detected in serum. Chronic infection with HBV is the result of an ineffective antiviral immune response towards the virus. In this review, we discuss the role of immune cells in chronic HBV infection. PMID- 26807387 TI - Correlation of Sperm Associated Antigen 11 (SPAG11) and its Isoforms with Varicocele in Rats. AB - BACKGROUND: We undertook this study to investigate the variation relationship of sperm associated antigen 11 (Spag11) mRNA expression and SPAG11E protein in the epididymis and spermatozoa of experimental left varicocele (ELV) rats. These findings could contribute to the understanding of the role of epididymal proteins in sperm functions and the mechanism of male infertility induced by varicocele. METHODS: The ELV model was established in adolescent male Sprague-Dawley rats. Four weeks after the operation, tissue distribution and changes in the expressions of Spag11 mRNA and SPAG11E protein caused by ELV in the whole of left epididymis and spermatozoa were studied using quantitative reverse transcription polymerase chain reaction (RT-QPCR), immunohistochemistry and immunofluorescence. Significant differences were identified using one-way ANOVA followed by Student Newman-Keuls test. Significance level (p) was fixed at 0.05. RESULTS: The expected product of Spag11 was 96 bp that amplified by RT-QPCR was detected in the epididymal tissue and spermatozoa. SPAG11E protein was confined mainly to the supranuclear region of the principal cells and the stereocilium of the epididymal epithelium, it was concentrated on the acrosome and the tail of spermatozoa except the terminal piece. Statistical analyses of the images and the data indicated that Spag11 mRNA and SPAG11E protein expressions in the left epididymis and spermatozoa of ELV rats presented a considerable decrease (p<0.001) compared with that of the corresponding control group. CONCLUSION: The expressions of Spag11 mRNA and SPAG11E protein declined markedly in ELV rats, which suggest that SPAG11E may not only play an important role in sperm maturation, but it may also be influenced by varicocele. PMID- 26807388 TI - What's new in critical illness and injury science? Nonaccidental burn injuries, child abuse awareness and prevention, and the critical need for dedicated pediatric emergency specialists: Answering the global call for social justice for our youngest citizens. PMID- 26807389 TI - Compound elevated skull fracture: Should we incorporate in skull fracture classification? PMID- 26807390 TI - Does erythropoietin reactivate bone marrow dysfunction in trauma hemorrhagic shock? PMID- 26807391 TI - Postoperative sciatic and femoral or saphenous nerve blockade for lower extremity surgery in anesthetized adults. AB - BACKGROUND: Guidelines warn of increased risks of injury when placing regional nerve blocks in the anesthetized adult but complications occurred in patients that received neither sedation nor local anesthetic. This restriction of nerve block administration places vulnerable categories of patients at risk of severe opioid induced side effects. Patient and operative technical factors can preclude use of preoperative regional anesthesia. The purpose of this study was to assess complications following sciatic popliteal and femoral or saphenous nerve blockade administered to anesthetized adult patients following foot and ankle surgery. MATERIALS AND METHODS: Postoperative patients administered general anesthesia received popliteal sciatic nerve blockade and either femoral or saphenous nerve blockade if operative procedures included medial incisions. Nerve blocks were placed with nerve stimulator or ultrasound guidance. A continuous nerve catheter was inserted if hospital admission was over 24 hours. Opioid analgesic supplementation was administered for inadequate pain relief. Postoperative pain scores and total analgesic requirements for 24 hours were recorded. Nerve block related complications were monitored for during the hospital admission and at follow up surgical clinic evaluation. RESULTS: 190 anesthetized adult patients were administered 357 nerve blocks. No major nerve injury or deficit was reported. One patient had numbness in the toes not ascribed to a specific nerve of the lower extremity. Perioperative opioid dose differences were noted between male and female and between opioid naive and tolerant patients. PMID- 26807392 TI - Endotracheal cuff pressure changes with change in position in neurosurgical patients. AB - BACKGROUND: Placement of a cuffed endotracheal tube for the administration of general anesthesia is routine. The cuff of the endotracheal tube is inflated with air to achieve an adequate seal to prevent micro-aspiration. Over inflation of the cuff can decrease the mucosal perfusion, leading to pressure necrosis and nerve palsies. Inadequate seal can lead to micro aspiration. So the cuff pressure has to be monitored and kept within the prescribed limits of 20-30 cms of water. AIM OF THE STUDY: To observe the effect of different positions on the endotracheal cuff pressure in patients undergoing neurosurgical procedures. MATERIALS AND METHODS: This is an observational study conducted on 70 patients undergoing neurosurgical procedures in various positions. After intubation, the cuff pressure was checked with a cuff pressure manometer, Endotest (Teleflex Medical, Rush) and adjusted to be within the allowable pressure limits as is the routine practice. The cuff pressure was checked again at three time points after achieving the final position with the head on pins, at the end of the procedure and before extubation. Various factors such as the age, position, duration of surgery were studied. There were no major complications like aspiration, stridor or hoarseness of voice post extubation in any of the patients. RESULTS: A significant decline in the cuff pressures were noted from the initial supine position to extubation (P < .001) in the supine group. Also a significant decline in the cuff pressures were found in the prone group from their initial intubated supine position to all the other three corresponding time points namely after final positioning (P < .001), at the end of the procedure (P < .001) and before extubation (P < .001). CONCLUSION: Cuff pressure has to be checked after achieving the final positioning of the patient and adjusted to the prescribed limits to prevent micro aspiration. PMID- 26807393 TI - Factors affecting adherence to treatment and follow-up of burns in children: A single centre experience. AB - AIM: Children are prone to burn injury. Burns can be seen as a part of child abuse. The aim of this study was to investigate the factors affecting adherence to the treatment of burn patients, and to emphasize the role of the physician in identifying children's non-accidental burn injuries. MATERIALS AND METHODS: Children who were hospitalized in the burn unit were analyzed retrospectively. Results were assessed for significance using the Chi-square test. RESULTS: A total of 189 patients were included. Some patients (n = 52; 27.5%) were discharged against medical advice (DAMA) before completion of treatment. Although we could not demonstrate a relationship between non-accidental etiology and DAMA group, it was significant that these patients did not contact the outpatient clinic after discharge. It was evident from records that two of these cases were abused. The reasoning of the parents in the DAMA group for the early discharge was siblings at home, financial and accommodation problems. CONCLUSION: Although burns in children commonly occur due to an accident, each burn case should be examined for a non-accidental etiology and findings suggesting abuse should be noted. Physicians should be alert for the detection of signs of burn related child abuse. PMID- 26807394 TI - The 2015 Academic College of Emergency Experts in India's INDO-US Joint Working Group White Paper on Establishing an Academic Department and Training Pediatric Emergency Medicine Specialists in India. AB - The concept of pediatric emergency medicine (PEM) is virtually nonexistent in India. Suboptimally, organized prehospital services substantially hinder the evaluation, management, and subsequent transport of the acutely ill and/or injured child to an appropriate facility. Furthermore, the management of the ill child at the hospital level is often provided by overburdened providers who, by virtue of their training, lack experience in the skills required to effectively manage pediatric emergencies. Finally, the care of the traumatized child often requires the involvement of providers trained in different specialities, which further impedes timely access to appropriate care. The recent recognition of Doctor of Medicine (MD) in Emergency Medicine (EM) as an approved discipline of study as per the Indian Medical Council Act provides an unprecedented opportunity to introduce PEM as a formal academic program in India. PEM has to be developed as a 3-year superspeciality course (in PEM) after completion of MD/Diplomate of National Board (DNB) Pediatrics or MD/DNB in EM. The National Board of Examinations (NBE) that accredits and administers postgraduate and postdoctoral programs in India also needs to develop an academic program - DNB in PEM. The goals of such a program would be to impart theoretical knowledge, training in the appropriate skills and procedures, development of communication and counseling techniques, and research. In this paper, the Joint Working Group of the Academic College of Emergency Experts in India (JWG-ACEE-India) gives its recommendations for starting 3-year DM/DNB in PEM, including the curriculum, infrastructure, staffing, and training in India. This is an attempt to provide an uniform framework and a set of guiding principles to start PEM as a structured superspeciality to enhance emergency care for Indian children. PMID- 26807395 TI - Complications during intrahospital transport of critically ill patients: Focus on risk identification and prevention. AB - Intrahospital transportation of critically ill patients is associated with significant complications. In order to reduce overall risk to the patient, such transports should well organized, efficient, and accompanied by the proper monitoring, equipment, and personnel. Protocols and guidelines for patient transfers should be utilized universally across all healthcare facilities. Care delivered during transport and at the site of diagnostic testing or procedure should be equivalent to the level of care provided in the originating environment. Here we review the most common problems encountered during transport in the hospital setting, including various associated adverse outcomes. Our objective is to make medical practitioners, nurses, and ancillary health care personnel more aware of the potential for various complications that may occur during patient movement from the intensive care unit to other locations within a healthcare facility, focusing on risk reduction and preventive strategies. PMID- 26807396 TI - Lip leishmaniasis: Clinical characteristics of 621 patients. PMID- 26807397 TI - High voltage electrical shock with multiple life-threatening injuries. PMID- 26807398 TI - Osborn waves in normothermic patient with hydropneumothorax and myocardial ischemia. PMID- 26807399 TI - Bioethical Issues in Providing Financial Incentives to Research Participants. AB - Offering research subjects financial incentives for their participation is a common practice that boosts recruitment but also raises ethical concerns, such as undue inducement, exploitation, and biased enrollment. This article reviews the arguments for providing participants with financial incentives, ethical concerns about payment, and approaches to establishing appropriate compensation levels. It also makes recommendations for investigators, institutions, and oversight committees. PMID- 26807400 TI - Retrospective study on factors affecting the prognosis in oral cancer patients who underwent surgical treatment only. AB - BACKGROUND: This study was performed to evaluate their 5-year survival rates and identify the factors affecting the prognosis of oral cancer patients who had undergone surgical treatment only. METHODS: Among 130 patients who were diagnosed with malignant tumor of oral, maxillofacial, and surgical treated in the Department of Oral and Maxillofacial Surgery at Chonnam National University Hospital within a period from January 2000 to December 2010, for 11 years, 84 patients were investigated who were followed up for more than 5 years after radical surgery; oral cancer is primary and received only surgical treatment. The survival rate according to gender, age, type and site of cancer, TNM stage, cervical lymph node metastasis and its stage, recurrence or metastasis, time of recurrence and metastasis, and differentiation were investigated and analyzed. RESULTS: Overall, 5-year survival rate in patients who received only surgical treatment was 81.2 %, and disease-specific 5-year survival rate was 83.1 %. The disease-specific 5-year survival rate based on TNM stage, metastasis of cervical lymph node, N stage, and presence of recurrence/metastasis was a significant difference (p < 0.05). The disease-specific 5-year survival rate based on sex, age, type of tumor, primary site, and differentiation was not a significant difference (p > 0.05). CONCLUSIONS: These results suggest that good survival rate can be obtained with surgical treatment only, and stage of oral cancer, cervical lymph node metastasis and stage, recurrence or metastasis, time of recurrence, and metastasis have a significant effect on survival rate in oral cancer patients. PMID- 26807401 TI - Tuning the mitochondrial rotary motor with light. AB - Skin surface temperature has been proposed as an in vivo clinical biomarker for monitoring the detrimental effect of biostimulatory laser applications. In some cases, such as wound healing and cosmetic applications, the target of the irradiation is the skin surface. In other cases, the light has to reach deeper tissues, for instance, during the irradiation of internal body organs. Prerequisite for reproducible biostimulatory effects is that the light intensity surpasses a minimum threshold. Because of the loss of light intensity caused by absorption and scattering, targeting deeper tissues always implies that the intensity at the skin surface will be much higher than that at the target site. Derived from laboratory experiments which showed that virtually the same light which produces biostimulatory effects in cells in vitro and tissues in vivo is instrumental in reducing the viscous friction in nanoconfined systems, we arrive to a new understanding of the effect of biostimulatory levels of light on mitochondria. One immediate result is insight into strategies which promise to maximize the biostimulatory effect and minimize potential phototoxic effects during treatment of deeper tissues. Such optimization strategies are also promising for experimental and therapeutic in vitro applications, in particular in combination with cell-friendly microenvironments. PMID- 26807402 TI - Raman spectroscopy in biomedicine: new advances in SERRS cancer imaging. PMID- 26807403 TI - Genetic modulation of oxytocin's effects in social functioning. PMID- 26807404 TI - Induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa. PMID- 26807405 TI - Is spread through alveolar spaces, the newly recognized pattern of invasion, a potential game changer in lung adenocarcinoma? PMID- 26807406 TI - Analytical assessment of the novel Maglumi squamous cell carcinoma antigen (SCCA) immunoluminometric assay. AB - BACKGROUND: The demand for routine measurement of squamous cell carcinoma antigen (SCCA) is rapidly increasing in clinical laboratories, due to the central role that this biomarker plays in staging and monitoring patients with various forms of squamous cell carcinomas (SCCs). METHODS: The present analytical evaluation of Maglumi SCCA was aimed to assess the imprecision, linearity and comparability against a widely used technique. RESULTS: The intra- and inter-assay imprecision was comprised between 2.6-4.2% and between 5.0-7.3%, respectively. The linearity of the test was excellent in the range of SCC values comprised between 1.0 and 18.0 ng/mL (r=0.998; P<0.001). A highly significant correlation was observed between Maglumi SCCA and BRAHMS Kryptor SCC in the range of values comprised between 0.44 and 15.18 ng/mL (r=0.960; P<0.001). The mean bias was 0.79 ng/mL (95% CI, 0.61-0.97) and the diagnostic agreement at the respective diagnostic cut offs was 95%. CONCLUSIONS: The results of this study confirm that Maglumi SCCA may be regarded as a suitable alternative to Kryptor SCC for routine and fully automated assessment of SCCA in clinical laboratories. PMID- 26807408 TI - Pre-operatively misdiagnosed undifferentiated embryonal sarcoma of the liver: analysis of 16 cases. AB - BACKGROUND: To investigate the clinical features of undifferentiated embryonal sarcoma of the liver (UESL) to improve its preoperative diagnostic accuracy. METHODS: The clinical, imaging, and histopathologic findings of 16 UESL patients whose disease was pathologically confirmed but preoperatively misdiagnosed were retrospectively analyzed. RESULTS: Among these 16 patients, 9 were clinically misdiagnosed as primary liver cancer, 3 as hepatoblastoma, and 4 as malignant hepatic mass. In 12 patients who were presented due to abdominal discomfort, ultrasound showed that predominantly solid lesions, whereas computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated predominantly cystic masses within irregular soft tissue. Contrast-enhanced imaging showed enhancement intralesional foci, multiple internal septations, and edges. The postoperative pathology showed the cutting surface of tumors was variegated, with solid and cystic gelatinous areas, hemorrhage, and necrosis. Intracytoplasmic hyaline globules were commonly present among cancer cells. CONCLUSIONS: UESL is a rare clinical condition without specific clinical manifestations. The inconsistencies between ultrasound and CT/MRI findings may be helpful to improve the preoperative diagnosis accuracy. PMID- 26807407 TI - A preliminary study on the relationship between circulating tumor cells count and clinical features in patients with non-small cell lung cancer. AB - BACKGROUND: To evaluate the clinical value of circulating tumor cells (CTC) count in peripheral venous blood of patients with non-small cell lung carcinoma (NSCLC). METHODS: A total of 50 NSCLC patients who were diagnosed in Wuxi No. 2 People's Hospital from January 2013 to December 2013 were selected as the NSCLC group, 35 patients with lung benign tumor as the benign group, and 28 healthy subjects as the normal control group. Venous blood samples (3 mL) were collected in all subjects for counting the CTC, and a result of >=8.7 was judged to be positive. The relationships between the positive rate of CTC and the age, sex, pathological type, and clinical stage of NSCLC were analyzed. RESULTS: CTC count was significantly higher in NSCLC group than in benign group and normal control group. In NSCLC patients, CTC count was not significantly correlated with sex, age, or the pathological type (P>0.05) but was closely related to clinical stage (P<0.01). Among NSCLC patients, CTC count significantly increased along with tumor progression. CONCLUSIONS: CTC count shows certain correlation with the clinical features of NSCLC and thus can, to certain extent, reflect the status of the disease. PMID- 26807409 TI - Clinical correlation between serum YKL-40 protein level and recurrence of non muscle invasive bladder cancer. AB - BACKGROUND: To explore the clinical correlation between serum YKL-40 protein level and recurrence of non-muscle invasive bladder cancer (NMIBC). METHODS: Totally 76 NMIBC patients (including 34 patients with confirmed recurrence and 42 patients without recurrence during the 2-year post-operative follow-up) and 31 healthy volunteers were recruited in this study. Blood samples were collected early in the morning, and serum YKL-40 protein levels of all these patients were analysed by using enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum YKL 40 protein levels were significantly higher in NMIBC patients than in healthy controls (P<0.001). Meanwhile, serum YKL-40 protein levels were found to be significantly higher in patients with recurrent NMIBC than those without tumor recurrence (P=0.001). CONCLUSIONS: Serum YKL-40 protein can be a reliable molecular marker for the clinical diagnosis of NMIBC recurrence. In particular, it can inform the post-operative management. PMID- 26807410 TI - Changes of center of rotation and femoral offset in total hip arthroplasty. AB - BACKGROUND: It is a challenge to reconstruct the center of rotation (COR) and femoroacetabular offset anatomically in total hip arthroplasty (THA). We addressed the controversy how we manage to preserve the COR and femoroacetabular offset with an uncemented total hip prosthesis implanted with free hand technique. METHODS: We analyzed a prospective series of 73 patients who underwent primary THA. The series was composed of 40 females and 33 males, mean age 64 years (range, 35-90 years). The reasons for THA were primary osteoarthritis (n=63) and developmental dysplasia of the hip (n=10). Pre- and postoperative X rays were done in a standardized format for anterior-posterior (AP) radiographs of the pelvis, and digitalized measurements were done using SectraTM. We compared preoperative measurements with the final outcome to determine changes in COR and femoral offset. RESULTS: We found that 40 patients had their COR and 34 patients had their femoral offset preserved within preoperative 5.0 mm limits. Twenty three patients had both their values of COR and femoral offset preserved within 5.0 mm limits. While a significant correlation was found between changes of femoral and global offset (r=0.786, P<0.001), there were no correlation between changes of acetabular and femoral offset (r=-0.027, P=0.822). CONCLUSIONS: Using an uncemented THA and free hand technique, there is a fair reproducibility of anatomy. The variations were mostly minor, but our results indicate a potential for better restoring the location of COR and femoral offset when planning and implanting an uncemented THA. PMID- 26807411 TI - Missing data exploration: highlighting graphical presentation of missing pattern. AB - Functions shipped with R base can fulfill many tasks of missing data handling. However, because the data volume of electronic medical record (EMR) system is always very large, more sophisticated methods may be helpful in data management. The article focuses on missing data handling by using advanced techniques. There are three types of missing data, that is, missing completely at random (MCAR), missing at random (MAR) and not missing at random (NMAR). This classification system depends on how missing values are generated. Two packages, Multivariate Imputation by Chained Equations (MICE) and Visualization and Imputation of Missing Values (VIM), provide sophisticated functions to explore missing data pattern. In particular, the VIM package is especially helpful in visual inspection of missing data. Finally, correlation analysis provides information on the dependence of missing data on other variables. Such information is useful in subsequent imputations. PMID- 26807412 TI - Nonintubated bilateral single port thoracoscopic sympathectomy in the context of an outpatient program, the least invasive management for hyperhidrosis surgery. AB - Primary hyperhidrosis is a frequent dysfunctional disorder characterized by excessive sweating in amounts greater than required for physiological needs. Surgery remains the mainstay of treatment when there is no response to medical therapies. Traditionally, thoracoscopic sympathectomy is performed routinely by means of general anesthesia with endotracheal intubation. Here we report the least invasive management for hyperhidrosis surgery, a nonintubated bilateral single port thoracoscopic sympathectomy in the context of an outpatient program. PMID- 26807414 TI - Highlighting the medical applications of 3D printing in Egypt. AB - Computer-assisted designing/computer-assisted manufacturing (CAD/CAM) technology has enabled medical practitioners to tailor physical models in a patient and purpose-specific fashion. It allows the designing and manufacturing of templates, appliances and devices with a high range of accuracy using biocompatible materials. The technique, nevertheless, relies on digital scanning (e.g., using intraoral scanners) and/or digital imaging (e.g., CT and MRI). In developing countries, there are some technical and financial limitations of implementing such advanced tools as an essential portion of medical applications. This paper focuses on the surgical and dental use of 3D printing technology in Egypt as a developing country. PMID- 26807413 TI - SOS response and its regulation on the fluoroquinolone resistance. AB - Bacteria can survive fluoroquinolone antibiotics (FQs) treatment by becoming resistant through a genetic change-mutation or gene acquisition. The SOS response is widespread among bacteria and exhibits considerable variation in its composition and regulation, which is repressed by LexA protein and derepressed by RecA protein. Here, we take a comprehensive review of the SOS gene network and its regulation on the fluoroquinolone resistance. As a unique survival mechanism, SOS may be an important factor influencing the outcome of antibiotic therapy in vivo. PMID- 26807415 TI - Niemann-Pick disease treatment: a systematic review of clinical trials. AB - The aim of this systematic review was to analyse all the published clinical trials assessing treatments for Niemann-Pick (NP) disease. At present there are only trials investigating the treatment of NP disease type C. Furthermore, there is no uniformity among studies in treatment outcomes or in data analysis and presentation of results. Miglustat is able to delay neurodegeneration, with greater benefits in patients with a late onset of the disease and beta cyclodextrin-hydroxypropyl (HBP-CD) can attenuate clinical symptoms. As for cholesterol-lowering drugs, the combination of lovastatin, cholestyramine and nicotinic acid is the most effective one for lowering cholesterolemia. Further research is much needed, and ongoing trials using enzyme replacement therapy might hopefully show promising results in the foreseeable future. PMID- 26807416 TI - Double segmentectomy for T4 lung cancer in a pulmonary-compromised patient. AB - Complete resection is the optimal treatment for primary lung cancer. The choice of surgical methods varies depending on tumor size, tumor location, and each patient's respiratory reserve. Currently, lobectomy with lymph node dissection is the gold standard for the surgical management of lung cancer. However, many thoracic surgical candidates also have chronic obstructive pulmonary disease or emphysema and thus present with minimal lung reserve. In the past few years, more reports have been published on the outcomes of patients who underwent anatomic segmentectomy for lung cancer. Herein we report the surgical outcomes of a patient with limited respiratory reserve, who underwent double segmentectomy. PMID- 26807417 TI - Robotic adrenalectomy for sigmoid colon cancer oligometastasis. AB - Solitary adrenal metastasis from colorectal cancer is rare with reported incidence from 3.1% to 14.4% in the literature. Conventionally, adrenal metastasis is considered as indicative of widespread systemic disease and hence treated with palliative intent. Surgical resection remains controversial although a median survival of 32 months was found in the largest reported case series. It has been postulated that surgical resection should be offered when the adrenal metastasis develops more than 6 months after the treatment of the primary tumor. For the metastatic lesions and potentially malignant lesions, role of minimally invasive surgery is still considered controversial. We are presenting a case of metachronous, solitary adrenal metastasis from sigmoid colon carcinoma treated surgically with curative intent. PMID- 26807418 TI - Charged particles for liver cancer. PMID- 26807419 TI - The evolving evidence for the efficacy and safety of charged particle therapy for hepatocellular carcinoma-a commentary. PMID- 26807420 TI - Charged particle therapy for hepatocellular carcinoma: a commentary on a recently published meta-analysis. PMID- 26807421 TI - Achievements and challenges for childhood cancer in China. PMID- 26807422 TI - Effect of age on cost-effectiveness of unicompartimental knee arthroplasty compared with total knee arthroplasty in the US. PMID- 26807423 TI - Biological characterization of soft tissue sarcomas. AB - Soft tissue sarcomas are neoplastic malignancies that typically arise in tissues of mesenchymal origin. The identification of novel molecular mechanisms leading to mesenchymal transformation and the establishment of new therapies and diagnostic biomarker has been hampered by several critical factors. First, malignant soft tissue sarcomas are rarely observed in the clinic with fewer than 15,000 newly cases diagnosed each year in the United States. Another complicating factor is that soft tissue sarcomas are extremely heterogeneous as they arise in a multitude of tissues from many different cell lineages. The scarcity of clinical materials coupled with its inherent heterogeneity creates a challenging experimental environment for clinicians and scientists. Faced with these challenges, there has been extremely limited advancement in clinical treatment options available to patients as compared to other malignant tumours. In order to glean insight into the pathobiology of soft tissue sarcomas, scientists are now using mouse models whose genomes have been specifically tailored to carry gene deletions, gene amplifications, and somatic mutations commonly observed in human soft tissue sarcomas. The use of these model organisms has been successful in increasing our knowledge and understanding of how alterations in relevant oncogenic and/or tumour suppressive signal cascades, i.e., interferon-gamma (IFN gamma), tumour protein 53 (TP53) and/or retinoblastoma (RB) pathway directly impact sarcomagenesis. It is the goal of many in the physiological community that the use of several mouse models will serve as powerful in vivo tools for further understanding of sarcomagenesis and potentially identify new diagnostic biomarker and therapeutic strategies against human soft tissue sarcomas. PMID- 26807424 TI - THE COP9 SIGNALOSOME, A NOVEL, ESSENTIAL REGULATOR OF SKELETAL DEVELOPMENT AND TUMORIGENESIS. AB - In recent years, the evolutionarily conserved complex named COP9 signalosome has emerged as an essential and versatile regulator of biological and pathological responses across species. Various components of COP9 signalosome, including CSN5 (also named JAB1), play critical roles in a wide array of developmental process. Using genetically engineered mouse models, our laboratory has recently identified CSN5/JAB1 as an essential regulator of skeletal development, in part through negatively regulating BMP signaling. BMP signaling is important for fracture healing and bone regeneration. BMPs have been used for treating acute fractures and for improving the success of spinal fusions. Therefore, harnessing the CSN5/JAB1-mediated inhibition of BMP signaling might be a novel strategy to improve the efficacy of BMP treatment and to reduce medical costs in the future. Furthermore, the up-regulation of COP9 signalosome has been associated with various cancers, including osteosarcoma. Thus, the COP9 signalosome can also be a valid target for treating osteosarcoma and other tumors. PMID- 26807425 TI - MESENCHYMAL STROMAL CELLS AND THEIR ORTHOPAEDIC APPLICATIONS. PMID- 26807426 TI - Human Immune Response Varies by the Degree of Relative Cryptococcal Antigen Shedding. AB - Background. Cerebrospinal fluid (CSF) cryptococcal glucuronoxylomannan antigen (CrAg) titers generally correlate with quantitative fungal culture burden; however, correlation is not precise. Some patients have higher CrAg titers with lower fungal burdens and vice versa. We hypothesized that the relative discordancy between CrAg titer and quantitative culture burden reflects the relative degree of CrAg shedding by Cryptococcus neoformans and is associated with human immune responses. Methods. One hundred ninety human immunodeficiency virus-infected individuals with cryptococcal meningitis were enrolled in Uganda and South Africa. We compared initial CSF CrAg titers relative to their CSF quantitative cultures to determine low (n = 58), intermediate (n = 68), or high (n = 64) CrAg shedders. We compared cytokines measured by Luminex multiplex assay on cryopreserved CSF and 10-week mortality across shedding groups using linear and logistic regression and distribution of genotypes by multilocus sequence typing. Results. The relative degree of CrAg shedding was positively associated with increasing CSF levels of the following: interleukin (IL)-6, IL-7, IL-8, and tumor necrosis factor-alpha (each P < 0.01), which are all secreted by antigen presenting cells and negatively associated with vascular endothelial growth factor (P = .01). In addition, IL-5, IL-13, granulocyte colony-stimulating factor, and macrophage chemotactic protein were decreased in low-CrAg shedders compared with intermediate shedders (each P <= .01). Type 1 T-helper cells (Th1) cytokine responses and 10-week mortality did not differ between the shedding groups. Cryptococcal genotypes were equally distributed across shedding groups. Conclusions. Discordancy between CrAg shedding and expected shedding based on quantitative fungal burden is associated with detectable immunologic differences in CSF, primarily among secreted cytokines and chemokines produced by antigen presenting cells and Th2. PMID- 26807427 TI - A Case Series of Acquired Drug Resistance-Associated Mutations in Human Immunodeficiency Virus-Infected Children: An Emerging Public Health Concern in Rural Africa. AB - The acquisition of drug-resistance mutations among African children living with in human immunodeficiency virus on antiretroviral treatment has been scarcely reported. This threatens the overall success of antiretroviral programs and the clinical outcomes of children in care. We present a well characterized series of children from rural Tanzania with acquired drug-resistance mutations to contribute to the better understanding of this emerging public health concern. PMID- 26807428 TI - Why Are Women Law Enforcement Officers More Burned-Out and What Might Help Them? PMID- 26807429 TI - The regulation of leukemia inhibitory factor. AB - Leukemia inhibitory factor (LIF), a secreted cytokine, plays an important role in a wide array of biological processes including inducing differentiation of leukemia cell, inflammatory response, neuronal development, embryonic implantation, stem cell self-renewal and cancer progression, etc. LIF exerts its biological functions mainly through the activation and regulation of JAK/STAT3, AKT, EKR1/2 and mTOR signal pathways. The expression levels of LIF are regulated by many different factors under different conditions in different tissue/cell types. For example, estrogen and p53 are important regulators for the high LIF production in uterine tissues at the implantation stage. Hypoxia plays a critical role in LIF overexpression in solid tumors. Many cytokines, including IL-6, IL 1beta, can also induce the LIF expression and production. In this review, we summarize the current understanding on the transcriptional regulation of LIF under various conditions. PMID- 26807430 TI - DNA Damage Sensitivity Assays in Caenorhabditis elegans. AB - C. elegans has served as a genetically tractable multicellular model system to examine DNA damage-induced genotoxic stress which threatens genome integrity. Importantly, the high degree of conservation shared between worms and humans offers the advantage that findings about DNA damage-induced cell cycle arrest/checkpoint response and DNA double-strand break repair in worms are applicable to human studies. Here, we describe simple DNA damage sensitivity assays to quantify the response of C. elegans to diverse types of DNA damaging agents. These assays have provided important insights into the mechanisms of function for factors such as ZTF-8 that are involved in DNA damage repair and response in the C. elegans germline. These DNA damage sensitivity assays rely on the straightforward readouts of either egg or larval lethality and involve the use of various DNA damaging agents. We use gamma-irradiation (gamma-IR), which produces DNA double-strand breaks (DSBs), camptothecin (CPT), which induces single-strand breaks, nitrogen mustard (HN2), which produces interstrand crosslinks (ICLs), hydroxyurea (HU), which results in replication fork arrest thus preventing DNA synthesis, and UV-C, which causes photoproducts (pyrimidine dimers). See Table 1. Comparisons between the relative sensitivity/resistance observed in, for example, mutants compared to wild type, for various DNA damaging agents allows for inferences regarding potential repair pathways being affected. PMID- 26807431 TI - To Grab and To Hold: Cultivating communal goals to overcome cultural and structural barriers in first generation college students' science interest. AB - Homogeneity within science limits creativity and discovery, and can feed into a perpetuating cycle of underrepresentation. From enhancing social justice to alleviating health and economic disadvantages, broadening participation in science is imperative. We focus here on first-generation students (FGS) and identify factors which grab and hold science interest among this underrepresented group. Might the culture and norms within science unintentionally limit FGS' participation? We argue that two distinct aspects of communal goals contribute to FGS' underrepresentation at different stages of the STEM pipeline: cultural perceptions of science as uncommunal (little emphasis on prosocial behavior and collaboration) and the uncommunal structure of STEM graduate education and training. Across 2 studies we investigated factors that catch (Study 1) and hold (Study 2) FGS' science interest. In Study 1, we find only when FGS believe that working in science will allow them to fulfill prosocial communal purpose goals are they more intrinsically interested in science. Yet, later in the pipeline science education devalues prosocial communal goals creating a structural mobility barrier among FGS. Study 2 found that FGS generally want to stay close to home instead of relocating to pursue a graduate education. For FGS (versus continuing-generation students), higher prosocial communal goal orientation significantly predicted lower residential mobility. We discuss implications for interventions to counteract the uncommunal science education and training culture to help improve access to FGS and other similarly situated underrepresented populations. PMID- 26807432 TI - Slot-Mode Optomechanical Crystals: A Versatile Platform for Multimode Optomechanics. AB - Cavity optomechanical systems are being studied for their potential in areas such as metrology, communications, and quantum information science. For a number of recently proposed applications in which multiple optical and mechanical modes interact, an outstanding challenge is to develop multimode architectures that allow flexibility in the optical and mechanical sub-system designs while maintaining the strong interactions that have been demonstrated in single-mode systems. To that end, we demonstrate slot-mode optomechanical crystals, devices in which photonic and phononic crystal nanobeams separated by a narrow slot are coupled via optomechanical interactions. These nanobeam pairs are patterned to confine a mechanical breathing mode at the center of one beam and a low-loss optical mode in the slot between the beams. This architecture affords great design flexibility towards multimode optomechanics, as well as substantial optomechanical coupling rates. We show this by producing slot-mode devices in stoichiometric Si3N4, with optical modes in the 980 nm band coupled to mechanical modes at 3.4 GHz, 1.8 GHz, and 400 MHz. We exploit the Si3N4 tensile stress to achieve slot widths down to 24 nm, which leads to enhanced optomechanical coupling, sufficient for the observation of optomechanical self-oscillations at all studied frequencies. We then develop multimode optomechanical systems with triple-beam geometries, in which two optical modes couple to a single mechanical mode, and two mechanical modes couple to a single optical mode. Taken together, these results demonstrate great flexibility in the design of multimode chip-scale optomechanical systems with large optomechanical coupling. PMID- 26807434 TI - Clarification of Bladder Cancer Disease States Following Treatment of Patients with Intravesical BCG. PMID- 26807433 TI - Reduction of p53 by knockdown of the UGT1 locus in colon epithelial cells causes an increase in tumorigenesis. AB - BACKGROUND & AIMS: The UDP-glucuronosyltransferases (UGTs) are part of the cells machinery that protects the tissues from a toxicant insult by environmental and host cell metabolites. We have investigated the mechanism behind tumor growth and UGT repression. METHODS: We initially silenced the Ugt1 locus in human colon cell lines and investigated markers and responses linked to p53 activation. To examine the role of the Ugt1 locus in p53-directed apoptosis and tumorigenesis, experiments were conducted to induce acute colon inflammation and chemical induced colon cancer in mice where we have selectively deleted the Ugt1 locus in the intestinal epithelial cells (Ugt1DeltaIEC mice). RESULTS: Knockdown of the UGT1A proteins by RNAi in human colon cancer cells and knockout of the Ugt1 locus in intestinal crypt stem cells reduces phosphorylated p53 activation and compromises the ability of p53 to control apoptosis. Targeted deletion of intestinal Ugt1 expression in Ugt1DeltaIEC mice represses colon inflammation induced p53 production and pro-apoptotic protein activation. When we induced colon cancer, the size and number of the tumors were significantly greater in the Ugt1DeltaIEC mice when compared to wild type mice. Furthermore, analysis of endoplasmic reticulum (ER) stress-related markers indicated that lack of UGT1A expression causes higher ER stress in intestinal epithelial cells and tissue, which may account for the lower expression of p53. CONCLUSIONS: Our results demonstrate that UGT1A expression is required to maintain and sustain p53 activation in stress-induced colon epithelial cells and has a significant impact on p53-mediated apoptosis and tumor suppression, thus protecting the colon tissue from neoplastic transformation. PMID- 26807435 TI - Internet Use and Adolescent Binge Drinking: Findings from the Monitoring the Future Study. AB - OBJECTIVE: To investigate the relation between Internet use and binge drinking during early and middle adolescence. METHODS: This is a cross-sectional study of a sub-sample of 8th and 10th graders from the Monitoring the Future (MtF) study, which annually surveys a nationally representative sample of U.S. youth on their attitudes, behaviors, and values. This study includes data from 21,170 8th and 24,362 10th graders who participated between 2007 and 2012 and were asked questions about Internet use and binge drinking. RESULTS: In fully adjusted models, we found a dose response relation between hours of recreational Internet use (i.e. outside work or school) and binge drinking which was stronger for 8th than 10th graders. Compared to <1 h of Internet use per week, odds ratios estimates for 1-5 h/week, 6-19 h/week, and 20 or more h/week were 1.24 (99% CI: 0.85, 1.82), 1.83 (1.28, 2.61), and 2.78 (1.99, 3.87) for 8th graders, respectively. For 10th graders, this same association was attenuated [estimated OR=1.06 (99% CI: 0.96, 1.16); 1.20 (1.03, 1.40); and 1.30 (1.07, 1.58), respectively]. CONCLUSIONS: Drawing on a nationally representative sample of U.S. youth, we find a significant, dose-response relation between Internet use and binge drinking. This relation was stronger in 8th graders versus 10th graders. Given that alcohol is the most abused substance among adolescents and binge drinking confers many health risks, longitudinal studies designed to examine the mediators of this relation are necessary to inform binge drinking prevention strategies, which may have greater impact if targeted at younger adolescents. PMID- 26807436 TI - Structure-Based Design and Biological Evaluation of Triphenyl Scaffold-Based Hybrid Compounds as Hydrolytically Stable Modulators of a LuxR-Type Quorum Sensing Receptor. AB - Many common bacterial pathogens utilize quorum sensing to coordinate group behaviors and initiate virulence at high cell densities. The use of small molecules to block quorum sensing provides a means of abrogating pathogenic phenotypes, but many known quorum sensing modulators have limitations, including hydrolytic instability and displaying non-monotonic dose curves (indicative of additional targets and/or modes of action). To address these issues, we undertook a structure-based scaffold-hopping approach to develop new chemical modulators of the LasR quorum sensing receptor in Pseudomonas aeruginosa. We combined components from a triphenyl derivative known to strongly agonize LasR with chemical moieties known for LasR antagonism and generated potent LasR antagonists that are hydrolytically stable across a range of pH values. Additionally, many of these antagonists do not exhibit non-monotonic dose effects, delivering probes that inhibit LasR across a wider range of assay conditions relative to known lactone-based ligands. PMID- 26807437 TI - High-Throughput Screen in Cryptococcus neoformans Identifies a Novel Molecular Scaffold That Inhibits Cell Wall Integrity Pathway Signaling. AB - Cryptococcus neoformans is one of the most important human fungal pathogens; however, no new therapies have been developed in over 50 years. Fungicidal activity is crucially important for an effective anticryptococal agent and, therefore, we screened 361,675 molecules against C. neoformans using an adenylate kinase release assay that specifically detects fungicidal activity. A set of secondary assays narrowed the set of hits to molecules that interfere with fungal cell wall integrity and identified three benzothioureas with low in vitro mammalian toxicity and good in vitro anticryptococcal (minimum inhibitory concentration = 4 MUg/mL). This scaffold inhibits signaling through the cell wall integrity MAP kinase cascade. Structure-activity studies indicate that the thiocarbonyl moiety is crucial for activity. Genetic and biochemical data suggest that benzothioureas inhibit signaling upstream of the kinase cascade. Thus, the benzothioureas appear to be a promising new scaffold for further exploration in the search for new anticryptococcal agents. PMID- 26807438 TI - Trehalose-Based Block Copolycations Promote Polyplex Stabilization for Lyophilization and in Vivo pDNA Delivery. AB - The development and thorough characterization of nonviral delivery agents for nucleic acid and genome editing therapies are of high interest to the field of nanomedicine. Indeed, this vehicle class offers the ability to tune chemical architecture/biological activity and readily package nucleic acids of various sizes and morphologies for a variety of applications. Herein, we present the synthesis and characterization of a class of trehalose-based block copolycations designed to stabilize polyplex formulations for lyophilization and in vivo administration. A 6-methacrylamido-6-deoxy trehalose (MAT) monomer was synthesized from trehalose and polymerized via reversible addition-fragmentation chain transfer (RAFT) polymerization to yield pMAT43. The pMAT43 macro-chain transfer agent was then chain-extended with aminoethylmethacrylamide (AEMA) to yield three different pMAT-b-AEMA cationic-block copolymers, pMAT-b-AEMA-1 (21 AEMA repeats), -2 (44 AEMA repeats), and -3 (57 AEMA repeats). These polymers along with a series of controls were used to form polyplexes with plasmids encoding firefly luciferase behind a strong ubiquitous promoter. The trehalose coated polyplexes were characterized in detail and found to be resistant to colloidal aggregation in culture media containing salt and serum. The trehalose polyplexes also retained colloidal stability and promoted high gene expression following lyophilization and reconstitution. Cytotoxicity, cellular uptake, and transfection ability were assessed in vitro using both human glioblastoma (U87) and human liver carcinoma (HepG2) cell lines wherein pMAT-b-AEMA-2 was found to have the optimal combination of high gene expression and low toxicity. pMAT-b AEMA-2 polyplexes were evaluated in mice via slow tail vein infusion. The vehicle displayed minimal toxicity and discouraged nonspecific internalization in the liver, kidney, spleen, and lungs as determined by quantitative polymerase chain reaction (qPCR) and fluorescence imaging experiments. Hydrodynamic infusion of the polyplexes, however, led to very specific localization of the polyplexes to the mouse liver and promoted excellent gene expression in vivo. PMID- 26807439 TI - Intraluminal Release of an Antifungal beta-Peptide Enhances the Antifungal and Anti-Biofilm Activities of Multilayer-Coated Catheters in a Rat Model of Venous Catheter Infection. AB - Candida albicans is the most prevalent cause of hospital-acquired fungal infections and forms biofilms on indwelling medical devices that are notoriously difficult to treat or remove. We recently demonstrated that the colonization of C. albicans on the surfaces of catheter tube segments can be reduced in vitro by coating them with polyelectrolyte multilayers (PEMs) that release a potent antifungal beta-peptide. Here, we report on the impact of polymer structure and film composition on both the inherent and beta-peptide-mediated ability of PEM coated catheters to prevent or reduce the formation of C. albicans biofilms in vitro and in vivo using a rat model of central venous catheter infection. Coatings fabricated using polysaccharide-based components [hyaluronic acid (HA) and chitosan (CH)] and coatings fabricated using polypeptide-based components [poly-l-lysine (PLL) and poly-l-glutamic acid (PGA)] both served as reservoirs for the loading and sustained release of beta-peptide, but differed substantially in loading and release profiles and in their inherent antifungal properties (e.g., the ability to prevent colonization and biofilm growth in the absence of beta-peptide). In particular, CH/HA films exhibited inherent antifungal and antibiofilm behaviors in vitro and in vivo, a result we attribute to the incorporation of CH, a weak polycation demonstrated to exhibit antimicrobial properties in other contexts. The antifungal properties of both types of films were improved substantially when beta-peptide was incorporated. Catheter segments coated with beta-peptide-loaded CH/HA and PLL/PGA films were both strongly antifungal against planktonic C. albicans and the formation of surface-associated biofilms in vitro and in vivo. Our results demonstrate that PEM coatings provide a useful platform for the design of new antifungal materials, and suggest opportunities to design multifunctional or dual-action platforms to prevent or reduce the severity of fungal infections in applied biomedical contexts or other areas in which fungal biofilms are endemic. PMID- 26807440 TI - Analyzing historical trends in breast cancer biomarker expression: a feasibility study (1947-2009). AB - BACKGROUND/OBJECTIVES: Determining long-term trends in tumor biomarker expression is essential for understanding aspects of tumor biology amenable to change. Limiting the availability of such data, currently used assays for biomarkers are relatively new. For example, assays for the estrogen receptor (ER), which are the oldest, extend back only to the 1970s. METHODS: To extend scant knowledge about the feasibility of obtaining long-term data on tumor biomarkers, we randomly selected 60 breast cancer cases (10 per decade) diagnosed between 1947-2009 among women members of the Kaiser Permanente Northern California health plan to obtain and analyze their formalin-fixed paraffin-embedded (FFPE) tumor specimens. For each tumor specimen, we created duplicate tissue microarrays for analysis. RESULTS: We located tumor blocks and pathology reports for 50 of the 60 cases (83%), from which we randomly sampled 5 cases per decade for biomarker analysis (n = 30). All 30 cases displayed excellent morphology and exhibited biomarkers compatible with histologic type and grade. Test-retest reliability was also excellent: 100% for ER; 97% for human epidermal growth factor receptor 2 and epidermal growth factor receptor; 93% for progesterone receptor and cytokeratin 5/6; and 90% for Ki67 and molecular phenotype; the kappa statistic was excellent (>0.9) for 4 of the 7 biomarkers, strong (0.6-0.8) for 2, and fair for only 1 (owing to low prevalence). CONCLUSIONS: These results indicate immunostaining for biomarkers commonly used to evaluate breast cancer biology and assign surrogate molecular phenotypes can reliably be employed on archival FFPE specimens up to 60 years old. PMID- 26807441 TI - A d-Amino Acid at the N-Terminus of a Protein Abrogates Its Degradation by the N End Rule Pathway. AB - Eukaryotes have evolved the ubiquitin (Ub)/proteasome system to degrade polypeptides. The Ub/proteasome system is one way that cells regulate cytosolic protein and amino acids levels through the recognition and ubiquitination of a protein's N-terminus via E1, E2, and E3 enzymes. The process by which the N terminus stimulates intracellular protein degradation is referred to as the N-end rule. Characterization of the N-end rule has been limited to only the natural l amino acids. Using a cytosolic delivery platform derived from anthrax lethal toxin, we probed the stability of mixed chirality proteins, containing one d amino acid on the N-terminus of otherwise all l-proteins. In all cases, we observed that one N-terminal d-amino acid stabilized the cargo protein to proteasomal degradation with respect to the N-end rule. We found that since the mixed chirality proteins were not polyubiquitinated, they evaded N-end-mediated proteasomal degradation. Evidently, a subtle change on the N-terminus of a natural protein can enhance its intracellular lifetime. PMID- 26807443 TI - Effect of 18F-FDG uptake time on lesion detectability in PET imaging of early stage breast cancer. AB - Prior reports have suggested that delayed FDG-PET oncology imaging can improve the contrast-to-noise ratio (CNR) for known lesions. Our goal was to estimate realistic bounds for lesion detectability for static measurements with one to four hours between FDG injection and image acquisition. Tumor and normal tissue kinetic model parameters were estimated from dynamic PET studies of patients with early stage breast cancer. These were used to generate time-activity curves (TACs) out to four hours, for which we assumed both nonreversible and reversible models with different rates of FDG dephosphorylation (k4). For each pair of tumor and normal tissue TACs, 600 PET sinogram realizations were generated, and images were reconstructed using OSEM. Test statistics for each tumor and normal tissue region of interest were output from the computer model observers and evaluated using an ROC analysis with the calculated AUC providing a measure of lesion detectability. For the nonreversible model (k4 = 0), the AUC increased in 11/23 (48%) of patients for one to two hours after the current standard post radiotracer injection imaging window of one hour. This improvement was driven by increased tumor/normal tissue contrast before the impact of increased noise due to radiotracer decay began to dominate the imaging signal. As k4 was increased from 0 to 0.01 min-1, the time of maximum detectability shifted earlier, as the decreasing FDG concentration in the tumor lowered the CNR. These results imply that delayed PET imaging may reveal low-conspicuity lesions that would have otherwise gone undetected. PMID- 26807445 TI - Using Dust Assessment Technology to Leverage Mine Site Manager-Worker Communication and Health Behavior: A Longitudinal Case Study. AB - Research continues to investigate barriers to managing occupational health and safety behaviors among the workforce. Recent literature argues that (1) there is a lack of consistent, multilevel communication and application of health and safety practices, and (2) social scientific methods are absent when determining how to manage injury prevention in the workplace. In response, the current study developed and tested a multilevel intervention case study at two industrial mineral mines to help managers and workers communicate about and reduce respirable silica dust exposures at their mine sites. A dust assessment technology, the Helmet-CAM, was used to identify and encourage communication about potential problem areas and tasks on site that contributed to elevated exposures. The intervention involved pre- and post-assessment field visits, four weeks apart that included multiple forms of data collection from workers and managers. Results revealed that mine management can utilize dust assessment technology as a risk communication tool to prompt and communicate about healthier behaviors with their workforce. Additionally, when workers were debriefed with the Helmet-CAM data through the device software, the dust exposure data can help improve the knowledge and awareness of workers, empowering them to change subtle behaviors that could reduce future elevated exposures to respirable silica dust. This case study demonstrates that incorporating social scientific methods into the application of health and safety management strategies, such as behavioral modification and technology integration, can leverage managers' communication practices with workers, subsequently improving health and safety behaviors. PMID- 26807444 TI - Uptake of 18F-DCFPyL in Paget's Disease of Bone, an Important Potential Pitfall in Clinical Interpretation of PSMA PET Studies. AB - Prostate-specific membrane antigen (PSMA)-targeted PET imaging is an emerging technique for evaluating patients with prostate cancer (PCa) in a variety of clinical contexts. As with any new imaging modality, there are interpretive pitfalls that are beginning to be recognized. In this image report, we describe the findings in a 63-year-old male with biochemically recurrent PCa after radical prostatectomy who was imaged with 18F-DCFPyL, a small molecule inhibitor of PSMA. Diffuse radiotracer uptake was noted throughout the sacrum, corresponding to imaging findings on contrast-enhanced CT, bone scan, and pelvic MRI consistent with Paget's disease of bone. The uptake of 18F-DCFPyL in Paget's disease is most likely due to hyperemia and increased radiotracer delivery. In light of the overlap in patients affected by PCa and Paget's, it is important for nuclear medicine physicians and radiologists interpreting PSMA PET/CT scans to be aware of the potential for this diagnostic pitfall. Correlation to findings on conventional imaging such as diagnostic CT and bone scan can help confirm the diagnosis. PMID- 26807447 TI - The Chronic Migraineur and Health Services: National Survey Results. AB - Chronic migraine is a costly and highly disabling condition that impacts millions of people in the United States. While chronic migraine is hypothesized to result from more infrequent forms of migraine, the precise mechanism by which this develops is still being researched. This study sought to better characterize the treatment patterns, disorder characteristics, and medical and disability profile of the chronic migraine population using the largest dataset of chronic migraineurs ever collected. The survey was started by 8,359 individuals and 4,787 met the inclusion criteria for diagnosed chronic migraine The number of stressful life events participants experienced due to their migraines related to number of therapies tried (p<0.00, eta2=0.215), depression (p<0.00, eta2=0.178), number of comorbidities (p<0.00, eta2=0.172), anxiety (p<0.00, eta2=0.162), number of physician visits in the past year (p<0.00, eta2=0.103), and chronic pain levels (p<0.00, eta2=0.077).. The results of this survey suggest that chronic migraineurs may misattribute aspects of psychiatric or medical comorbidities to their chronic migraines. Further, the sample underutilized mental health services and were unsatisfied with their migraine treatments. Providers to chronic migraineurs should ensure that patients are receiving appropriate mental health care in order to alleviate psychological distress as well as to potentially lessen negative life events previously associated with migraine symptoms. PMID- 26807448 TI - Guest Editors' Introduction to the Special Section on Award-Winning Papers from the IEEE Conference on Computer Vision and Pattern Recognition 2009 (CVPR 2009). PMID- 26807446 TI - Paediatric HIV infection in the 'omics era: defining transcriptional signatures of viral control and vaccine responses. AB - Modern technologies and their increased accessibility have shifted 'benchtop' medical research to the larger dimension of 'omics. The huge amount of data derived from gene expression and sequencing experiments has propelled physicians, basic scientists and bioinformaticians towards a common goal to transform 'big data' into predictive constructs that are readily available and will offer clinical utility. Although most of the studies available in the literature have been performed on healthy subjects and in peripheral blood mononuclear cells (PBMC), which are a heterogenous and extremely variable pool of cells, scientists are now trying to address mechanistic questions in purified cell subsets in pathological conditions. In the field of HIV, few attempts have been made to comprehensively evaluate gene-expression profiles of infected patients with different disease status. With the view of discovering a path towards remission or viral eradication, perinatally HIV-infected children represent a unique model. In fact the well-defined time of infection and the resulting opportunity to start early treatment, thereby generating a smaller size of viral reservoir and a more intact immune system, allow for investigation of therapeutic strategies to defeat the virus. In this scenario, 'transcriptomic' or gene expression technologies and supporting bioinformatics applications need to be strategically integrated to provide novel information about immune correlates of virus control following treatment interruption. Here we review modern techniques for gene expression analysis and discuss the best transcriptomic strategies applicable to the field of functional cure in paediatric HIV infection. PMID- 26807449 TI - First, Don't Be a Tourist. PMID- 26807450 TI - Annals Q&A With Dr. Steven Stack. PMID- 26807451 TI - Infectious Disease/CDC Update. Update on Emerging Infections: News From the Centers for Disease Control and Prevention. PMID- 26807453 TI - Latest trends in the pet food industry. PMID- 26807452 TI - William Erwin Paul (1936-2015). PMID- 26807454 TI - Little things count. PMID- 26807442 TI - Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC). AB - Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68-0.90, p = 5.59 * 10-4]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1, may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways. PMID- 26807455 TI - Supporting the journey is our business. PMID- 26807456 TI - Graduate Mentoring Program hits the ground running. PMID- 26807457 TI - Gearing up for Antibiotic Awareness Week. PMID- 26807458 TI - Risks associated with clients seeing multiple veterinarians. PMID- 26807459 TI - Emergency Animal Diseases Bulletin--protecting Australia from CSF. PMID- 26807460 TI - Wildlife forensic science. PMID- 26807461 TI - Case study: law and the illegal wildlife trade in China. PMID- 26807462 TI - The Koala Genome Project. PMID- 26807463 TI - Best in the West for vets. PMID- 26807464 TI - Keeping Australia rabies free. PMID- 26807465 TI - Rabies awareness in Kathmandu Valley, Nepal. PMID- 26807467 TI - A leap forward for SASH. PMID- 26807466 TI - Angus Adkins, equine surgeon. PMID- 26807468 TI - Business restructuring and how it affects you: part 2. PMID- 26807469 TI - ASCO, Others Design Tools To Measure the Worth of Drugs. PMID- 26807470 TI - Philadelphia's Fox Chase In Pursuit of Fewer Readmissions. PMID- 26807471 TI - On or off track? 2016 could be the year that value-based payment arrives--or maybe not. PMID- 26807472 TI - Sticker shock waves: Players to respond to drug priciness. PMID- 26807474 TI - Too much of a good thing: Overdiagnosis to get its due. PMID- 26807473 TI - The hunger gains: Appetite for quality to grow. PMID- 26807475 TI - Growing testiness: Disagreements between insurers, labs about new molecular tests. PMID- 26807476 TI - Shape Modification of Water-in-CO2 Microemulsion Droplets through Mixing of Hydrocarbon and Fluorocarbon Amphiphiles. AB - An oxygen-rich hydrocarbon (HC) amphiphile has been developed as an additive for supercritical CO2 (scCO2). The effects of this custom-designed amphiphile have been studied in water-in-CO2 (w/c) microemulsions stabilized by analogous fluorocarbon (FC) surfactants, nFG(EO)2, which are known to form spherical w/c microemulsion droplets. By applying contrast-variation small-angle neutron scattering (CV-SANS), evidence has been obtained for anisotropic structures in the mixed systems. The shape transition is attributed to the hydrocarbon additive, which modifies the curvature of the mixed surfactant films. This can be considered as a potential method to enhance physicochemical properties of scCO2 through elongation of w/c microemulsion droplets. More importantly, by studying self-assembly in these mixed systems, fundamental understanding can be developed on the packing of HC and FC amphiphiles at water/CO2 interfaces. This provides guidelines for the design of fluorine-free CO2 active surfactants, and therefore, practical industrial scale applications of scCO2 could be achieved. PMID- 26807477 TI - Cytoplasmic Heme-Binding Protein (HutX) from Vibrio cholerae Is an Intracellular Heme Transport Protein for the Heme-Degrading Enzyme, HutZ. AB - HutZ is a cytoplasmic heme-binding protein from Vibrio cholerae. Although we have previously identified HutZ as a heme-degrading enzyme [Uchida, T., et al. (2012) Chem. Commun. 48, 6741-6743], the heme transport protein for HutZ remained unknown. To identify the heme transport protein for HutZ, we focused on the heme utilization operon, hutWXZ. To this end, we constructed an expression system for HutX in Escherichia coli and purified it to homogeneity. An absorption spectral analysis demonstrated that HutX binds heme with a 1:1 stoichiometry and a dissociation constant of 7.4 nM. The crystal structure of HutX displays a fold similar to that of the homologous protein, ChuX, from E. coli O157:H7. A structural comparison of HutX and ChuX, and resonance Raman spectra of heme-HutX, suggest that the axial ligand of the ferric heme is Tyr90. The heme bound to HutX is transferred to HutZ with biphasic dissociation kinetics of 8.3 * 10(-2) and 1.5 * 10(-2) s(-1), values distinctly larger than those for transfer from HutX to apomyoglobin. Surface plasmon resonance experiments confirmed that HutX interacts with HutZ with a dissociation constant of ~400 MUM. These results suggest that heme is transferred from HutX to HutZ via a specific protein-protein interaction. Therefore, we can conclude that HutX is a cytoplasmic heme transport protein for HutZ. PMID- 26807478 TI - Prevention of vascular smooth muscle cell proliferation and injury-induced neointimal hyperplasia by CREB-mediated p21 induction: An insight from a plant polyphenol. AB - Cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element (CRE)-binding protein (CREB) signaling cascade negatively regulates platelet-derived growth factor BB (PDGF-BB)-induced smooth muscle cell (SMC) proliferation, which is a critical event in the initiation and development of restenosis and atherosclerotic lesions. Salvianolic acid A (SAA) is one of the most abundant polyphenols extracted from salvia. The aim of this study is to investigate whether SAA exerts an action on PDGF-BB-induced proliferation via cAMP/PKA/CREB mechanism. SAA blunts PDGF-BB-induced human umbilical artery smooth muscle cell (hUASMC) proliferation via p21 induction, as evidenced by its increased mRNA and protein expression levels. The SAA-induced upregulation of p21 involves the cAMP/PKA signaling pathway; a cAMP analog mimicked the effects of SAA and a specific cAMP/PKA inhibitor opposed these effects. SAA also activated CREB, including phosphorylation at Ser133, and induced its nuclear translocation. Deletion and mutational analysis of p21 promoters, co-immunoprecipitation, and western blot analysis showed that CRE is essential for SAA-induced p21 protein expression. Transfection of dominant-negative CREB (mutated Ser133) plasmids into hUASMCs attenuated SAA-stimulated p21 expression. SAA upregulated p21 expression and activated CREB in the neointima of balloon-injured arteries in vivo. Our results indicate that SAA promotes p21 expression in SMCs through the cAMP/PKA/CREB signaling cascade in vitro and prevents injury-induced neointimal hyperplasia. PMID- 26807479 TI - Interactions of human P-glycoprotein transport substrates and inhibitors at the drug binding domain: Functional and molecular docking analyses. AB - Rhodamine 123 (R123) transport substrate sensitizes P-glycoprotein (P-gp) to inhibition by compound 2c (cis-cis) N,N-bis(cyclohexanolamine)aryl ester isomer in a concentration-dependent manner in human MDR1-gene transfected mouse T lymphoma L5178 cells as shown previously. By contrast, epirubicin (EPI) concentration changes left unaltered 2c IC50 values of EPI efflux. To clarify this discrepancy, defined molecular docking (DMD) analyses of 12 N,N bis(cyclohexanolamine)aryl esters, the highly flexible aryl ester analog 4, and several P-gp substrate/non-substrate inhibitors were performed on human P-gp drug or nucleotide-binding domains (DBD or NBD). DMD measurements yielded lowest binding energy (LBE, kcal/mol) values (mean +/- SD) ranging from -11.8 +/- 0.54 (valspodar) to -3.98 +/- 0.01 (4). Lys234, Ser952 and Tyr953 residues formed H bonds with most of the compounds. Only 2c docked also at ATP binding site (LBE value of -6.9 +/- 0.30 kcal/mol). Inhibition of P-gp-mediated R123 efflux by 12 N,N-bis(cyclohexanolamine)aryl esters and 4 significantly correlated with LBE values. DMD analysis of EPI, (3)H-1EPI, (3)H-2EPI, (14)C-1EPI, (14)C-2EPI, R123 and 2c before and after previous docking of each of them indicated that pre docking of either 2c or EPI significantly reduced LBE of both EPI and R123, and that of both (3)H-2EPI and (14)C-2EPI, respectively. Since the clusters of DBD amino acid residues interacting with EPI were different, if EPI docked alone or after pre-docking of EPI or 2c, the existence of alternative secondary binding site for EPI on P-gp is credible. In conclusion, 2c may allocate the drug-binding pocket and reduce strong binding of EPI and R123 in agreement with P-gp inhibition experiments, where 2c reduced efflux of EPI and R123. PMID- 26807481 TI - Correction to Phenyl Ether- and Aniline-Containing 2-Aminoquinolines as Potent and Selective Inhibitors of Neuronal Nitric Oxide Synthase. PMID- 26807480 TI - Glucagon-like peptide-1 inhibits vascular smooth muscle cell dedifferentiation through mitochondrial dynamics regulation. AB - Glucagon-like peptide-1 (GLP-1) is a neuroendocrine hormone produced by gastrointestinal tract in response to food ingestion. GLP-1 plays a very important role in the glucose homeostasis by stimulating glucose-dependent insulin secretion, inhibiting glucagon secretion, inhibiting gastric emptying, reducing appetite and food intake. Because of these actions, the GLP-1 peptide mimetic exenatide is one of the most promising new medicines for the treatment of type 2 diabetes. In vivo treatments with GLP-1 or exenatide prevent neo-intima layer formation in response to endothelial damage and atherosclerotic lesion formation in aortic tissue. Whether GLP-1 modulates vascular smooth muscle cell (VSMC) migration and proliferation by controlling mitochondrial dynamics is unknown. In this report, we showed that GLP-1 increased mitochondrial fusion and activity in a PKA-dependent manner in the VSMC cell line A7r5. GLP-1 induced a Ser-637 phosphorylation in the mitochondrial fission protein Drp1, and decreased Drp1 mitochondrial localization. GLP-1 inhibited PDGF-BB-induced VSMC migration and proliferation, actions inhibited by overexpressing wild type Drp1 and mimicked by the Drp1 inhibitor Mdivi-1 and by overexpressing dominant negative Drp1. These results show that GLP-1 stimulates mitochondrial fusion, increases mitochondrial activity and decreases PDGF-BB-induced VSMC dedifferentiation by a PKA/Drp1 signaling pathway. Our data suggest that GLP-1 inhibits vascular remodeling through a mitochondrial dynamics-dependent mechanism. PMID- 26807482 TI - Identification of important genes associated with total cholesterol using bioinformatics analysis. AB - AIM: The aim of this study was to identify related genes for total cholesterol (TC) and evaluate the functional relevance to provide evidences for prioritizing these genes. MATERIALS & METHODS: We performed an initial gene-based association study in about 188,578 individuals. Furthermore, we performed bioinformatics analyses to support the identified genes. RESULTS: A total of 22,098 genes were analyzed for TC levels in gene-based association analysis and 433 of them were found to be significant after Bonferroni correction (p < 2.3 * 10(-6)). CONCLUSION: The evidence obtained from the analyses of this study signified the importance of many known genes as well as some novel genes, for example, NR1I2, STARD3 and FN1. The findings might provide more insights into the genetic basis of lipid metabolism. PMID- 26807483 TI - Diverse Natural Products from Dichlorocyclobutanones: An Evolutionary Tale. AB - 11-Nor PGE2 was prepared in our laboratory several years ago and used to obtain the corresponding ring-expanded gamma-butyrolactam, gamma-butyrolactone, and cyclopentanone derivatives. The conversion of a cyclobutanone into a cyclopentanone had relatively little precedent and merited further study. It was soon found that the presence of a single chlorine adjacent to the carbonyl not only greatly accelerated the reaction with ethereal diazomethane, but also substantially enhanced its regioselectivity; not surprisingly, a second chlorine further increased both. The confluence of this finding and the discovery by Krepski and Hassner that the presence of phosphorus oxychloride significantly improved the Zn-mediated dehalogenation procedure for the preparation of alpha,alpha-dichlorocyclobutanones from olefins provided the starting point for decades' worth of exciting adventures in natural product synthesis. A wide variety of naturally occurring 5-membered carbocycles (e.g., hirsutanes, cuparenones, bakkanes, guaianolides, azulenes) could thus be prepared by using dichloroketene-olefin cycloaddition, followed by regioselective one-carbon ring expansion with diazomethane. Importantly, it was also found that natural gamma butyrolactones (e.g., beta-oxygenated gamma-butyrolactones, lactone fatty acids) could be secured through regioselective Baeyer-Villiger oxidation of cycloadducts with m-CPBA and that naturally occurring gamma-butyrolactam derivatives (e.g., amino acids, pyrrolidines, pyrrolizidines, indolizidines) could be efficiently obtained by regioselective Beckmann ring expansion of the adducts with O (mesitylenesulfonyl)hydroxylamine (Tamura's reagent). These 5-membered carbocycles, gamma-butyrolactones, and gamma-butyrolactam derivatives were generally secured in enantiopure form through the use of either intrinsically chiral olefins or olefins bearing Stericol, a highly effective chiral auxiliary developed specifically for this "three-atom olefin annelation" approach. In addition, considerable useful chemistry has been developed in the context of this synthesis program. This includes new methods for olefin vicinal dicarboxylation, beta-methylene-gamma-butyrolactonization, gamma-butyrolactone and delta valerolactone alpha-methylenations, transesterification, angelic ester synthesis, chiral enol and ynol ether preparations, dichloroacetylene synthesis, and trans, trans hydroxy triad introduction. This versatile dichlorocyclobutanone-centered approach to natural product synthesis, together with the attendant new methods that have been developed, forms the basis of this Account, which is presented as an evolutionary tale. It is hoped that the Account will stimulate other research groups to seek to exploit the rich chemistry of dichlorocyclobutanones for possible solutions to problems in organic synthesis. PMID- 26807484 TI - Evolving a Nelder-Mead Algorithm for Optimization with Genetic Programming. AB - We used genetic programming to evolve a direct search optimization algorithm, similar to that of the standard downhill simplex optimization method proposed by Nelder and Mead ( 1965 ). In the training process, we used several ten dimensional quadratic functions with randomly displaced parameters and different randomly generated starting simplices. The genetically obtained optimization algorithm showed overall better performance than the original Nelder-Mead method on a standard set of test functions. We observed that many parts of the genetically produced algorithm were seldom or never executed, which allowed us to greatly simplify the algorithm by removing the redundant parts. The resulting algorithm turns out to be considerably simpler than the original Nelder-Mead method while still performing better than the original method. PMID- 26807485 TI - Chemical Structures of Plant Hydrolyzable Tannins Reveal Their in Vitro Activity against Egg Hatching and Motility of Haemonchus contortus Nematodes. AB - The use of synthetic drugs against gastrointestinal nematodes of ruminants has led to a situation where resistance to anthelmintics is widespread, and there is an urgent need for alternative solutions for parasite control. One promising approach is to use polyphenol-rich bioactive plants in animal feeds as natural anthelmintics. In the present work, the in vitro activity of a series of 33 hydrolyzable tannins (HTs) and their hydrolysis product, gallic acid, against egg hatching and motility of L1 and L2 stage Haemonchus contortus larvae was studied. The effect of the selected compounds on egg and larval structure was further studied by scanning electron microscopy. The results indicated clear relationships between HT structure and anthelmintic activity. While HT size, overall flexibility, the types and numbers of functional groups, together with the linkage types between monomeric HTs affected the activity differently, the optimal structure was found with pentagalloylglucose. PMID- 26807486 TI - Biostable insect kinin analogs reduce blood meal and disrupt ecdysis in the blood gorging Chagas' disease vector, Rhodnius prolixus. AB - Rhodnius prolixus is a blood-gorging hemipteran that takes blood meals that are approximately 10 times its body weight. This blood meal is crucial for growth and development and is needed to ensure a successful molt into the next instar. Kinins are a multifunctional family of neuropeptides which have been shown to play a role in the control of feeding in a variety of insects. In this study, two biostable Aib-containing kinin analogs were tested to see if they interfere with blood-feeding and subsequent development into the next instar. One of the analogs, 1729 (Ac-R[Aib]FF[Aib]WGa), had no effect on the size of the blood meal or on the subsequent molting of the insect into the next instar. This analog also did not interfere with either short-term or long-term diuresis. The second analog, 1728 ([Aib]FF[Aib]WGa), appeared to be an antifeedant. Insects feeding on blood containing this analog (15MUM) only consumed 60% of the blood meal taken by insects fed on blood without analog. Insects feeding on blood containing 1728 had a slower rate of rapid diuresis (diuresis in the first 3-5h after feeding) leading to less urine being excreted by 5days post feeding. The consequence of these effects was that insects fed on 1728 did not molt. This data indicates that the biostable Aib-containing analog 1728 disrupts normal growth and development in the blood-feeding insect, R. prolixus. PMID- 26807487 TI - The European Society of Gynecologic Oncology (ESGO) 19th biannual meeting: Overview and summary of selected topics. PMID- 26807488 TI - Operability and chemotherapy responsiveness in advanced low-grade serous ovarian cancer. An analysis of the AGO Study Group metadatabase. AB - OBJECTIVE: Since almost two decades standard 1st-line chemotherapy for advanced ovarian cancer (AOC) has been a platinum/taxane combination. More recently, this general strategy has been challenged because different types of AOC may not benefit homogenously. Low-grade serous ovarian cancer (LGSOC) is one of the candidates in whom efficacy of standard chemotherapy should be revised. METHODS: This study is an exploratory case control study of the AGO-metadatabase of 4 randomized phase III trials with first-line platinum combination chemotherapy without any targeted therapy. Patients with advanced FIGO IIIBIV low-grade serous ovarian cancer were included and compared with control cases having high-grade serous AOC. RESULTS: Out of 5114 patients in this AGO database 145 (2.8%) had LGSOC and of those thirty-nine (24.1%) had suboptimal debulking with post operative residual tumor >1cm, thus being eligible for response evaluation. An objective response was observed in only 10 patients and this 23.1% response rate (RR) was significantly lower compared to 90.1% RR in the control cohort of high grade serous ovarian cancer (HGSOC) (p<0.001). Both, LGSOC and HGSOC patients who underwent complete cytoreduction had significantly better progression free survival (PFS) and overall survival (OS) in comparison to those with residuals after primary surgery, accordingly (p<0.001). CONCLUSIONS: Our observation indicates that low-grade serous cancer is not as responsive to platinum-taxane based chemotherapy as high-grade serous AOC. In contrast, surgical debulking showed a similar impact on outcome in both types of AOC thus indicating different roles for both standard treatment modalities. Systemic treatment of low grade serous AOC urgently warrants further investigations. PMID- 26807489 TI - Self-rated health in patients with rheumatoid arthritis is associated with health related quality of life but not with clinical variables. AB - OBJECTIVES: Self-rated health (SRH) is a well-known overall health status measure used in the general population but it is rarely examined in a clinical setting. We assessed SRH-related factors in clinic-based patients with rheumatoid arthritis (RA). METHOD: The study included 123 consecutive outpatients treated in 1998-1999. Patient questionnaires, including a single SRH item, sociodemographics, the Health Assessment Questionnaire (HAQ) for functional ability, and the Nottingham Health Profile (NHP) for health-related quality of life (QoL), were collected at baseline. Comorbidities were measured by the Charlson Comorbidity Index (CCI) and data on the use of drugs and surgery for RA were verified from medical records and by querying patients. Factors associated with SRH were examined using regression models with the propensity score as the covariate. Mortality rates were collected up to 31 December 2014. Hazard ratios (HRs) were used to estimate SRH-associated mortality. RESULTS: In univariate analysis, poor SRH was associated with higher age and poorer patient-reported outcomes (PROs) but not with gender and clinical variables. After adjustment for the propensity score, the NHP dimensions for pain, energy, emotional reactions, and mobility remained significantly associated with SRH. The age- and sex adjusted HR for death was 2.38 [95% confidence interval (CI) 1.13-5.04, p = 0.034] for the patients with poor vs. good SRH. The propensity score-adjusted HR for death was 1.69 (95% CI 0.74-3.86, p = 0.21). Conclusions In patients with RA, SRH was associated with health-related QoL dimensions, reflecting patients' well-being rather than clinical factors. During the 16 years of follow-up, SRH had no independent association with mortality. PMID- 26807490 TI - Bystander Intervention Prior to The Arrival of Emergency Medical Services: Comparing Assistance across Types of Medical Emergencies. AB - OBJECTIVE: To determine the situational circumstances associated with bystander interventions to render aid during a medical emergency. METHODS: This study examined 16.2 million Emergency Medical Service (EMS) events contained within the National Emergency Medical Services Information System. The records of patients following a 9-1-1 call for emergency medical assistance were analyzed using logistic regression to determine what factors influenced bystander interventions. The dependent variable of the model was whether or not a bystander intervened. RESULTS: EMS providers recorded bystander assistance 11% of the time. The logistic regression model correctly predicted bystander intervention occurrence 71.4% of the time. Bystanders were more likely to intervene when the patient was male (aOR = 1.12, 95% CI = 1.12-1.3) and if the patient was older (progressive aOR = 1.10, 1.46 age group 20-29 through age group 60-99). Bystanders were less likely to intervene in rural areas compared to urban areas (aOR = 0.58, 95% CI = 0.58-0.59). The highest likelihood of bystander intervention occurred in a residential institution (aOR = 1.86, 95% CI = 1.85-1.86) and the lowest occurred on a street or a highway (aOR = 0.96, 95% CI = 0.95-0.96). Using death as a reference group, bystanders were most likely to intervene when the patient had cardiac distress/chest pain (aOR = 11.38, 95% CI = 10.93-11.86), followed by allergic reaction (aOR = 7.63, 95% CI = 7.30-7.99), smoke inhalation (aOR = 6.65, 95% CI = 5.98-7.39), and respiration arrest/distress (aOR = 6.43, 95% CI = 6.17 6.70). A traumatic injury was the most commonly recorded known event, and it was also associated with a relatively high level of bystander intervention (aOR = 5.81, 95% CI = 5.58-6.05). The type of injury/illness that prompted the lowest likelihood of bystander assistance was Sexual Assault/Rape (aOR = 1.57, 95% CI = 1.32-1.84) followed by behavioral/psychiatric disorder (aOR = 1.64, 95% CI = 1.57 1.71). CONCLUSION: Bystander intervention varies greatly on situational factors and the type of medical emergency. A higher risk of patient death is likely to prompt bystander action. These novel study results can lead to more effective first aid training programs. KEY WORDS: bystander; EMS; rural; cardiac distress; trauma. PMID- 26807491 TI - Novel bioadhesive polymers as intra-articular agents: Chondroitin sulfate cysteine conjugates. AB - The aim of this study was to generate and characterize a chondroitin sulfate cysteine conjugate (CS-cys) as a novel bioadhesive agent for intra-articular use. Mucoadhesive properties of synthesized CS-cys were investigated by rheological measurement of polymer-mucus mixture and rotating cylinder method, while bioadhesive features of CS-cys on porcine articular cartilage were evaluated via tensile studies. Thiolation was achieved by attachment of l-cysteine to CS via amide bond formation mediated by carbodiimide as a coupling reagent. The conjugate exhibited 421.17+/-35.14 MUmol free thiol groups per gram polymer. The reduced CS-cys displayed 675.09+/-39.67 MUmol free thiol groups per gram polymer after disulfide bonds reduction using tris(2-carboxyethyl)phosphine hydrochloride. The increase in dynamic viscosity of thiolated CS due to oxidative disulfide bond formation was demonstrated using capillary viscometer. The combination of CS-cys and mucus led to 4.57-fold increase in dynamic viscosity in comparison with mucus control. Furthermore, adhesion time to porcine mucosa of CS cys-based test disk was enhanced by 2.48-fold compared to unmodified CS as measured by rotating cylinder method suggesting the interaction between thiomers and mucus gel layer via disulfide bonds formation. Tensile studies of thiolated CS on porcine articular cartilage showed 5.37- and 1.76-fold increase in the total work of adhesion and the maximum detachment force, respectively, in comparison with unmodified CS indicating bioadhesive features of CS-cys. Cytotoxicity of CS-cys was assessed in Caco-2 cells and rat primary articular chondrocytes using MTT and LDH release assay, thereby showing the safety of CS cys at a concentration of 0.25% (w/v) in Caco-2 cells. Furthermore, 0.1% of CS cys was found non-toxic to rat primary articular chondrocytes. According to these results, CS-cys provides improved bioadhesive properties that might be useful as an intra-articular agent for treatment of osteoarthritis. PMID- 26807492 TI - Identification of Ion-Pair Structures in Solution by Vibrational Stark Effects. AB - Ion pairing is a fundamental consideration in many areas of chemistry and has implications in a wide range of sciences and technologies that include batteries and organic photovoltaics. Ions in solution are known to inhabit multiple possible states, including free ions (FI), contact ion pairs (CIP), and solvent separated ion pairs (SSIP). However, in solutions of organic radicals and nonmetal electrolytes, it is often difficult to distinguish between these states. In the first part of this work, we report evidence for the formation of SSIPs in low-polarity solvents and distinct measurements of CIP, SSIP, and FI, by using the nu(C=N) infrared (IR) band of a nitrile-substituted fluorene radical anion. Use of time-resolved IR detection following pulse radiolysis allowed us to unambiguously assign the peak of the FI. In the presence of nonmetal electrolytes, two distinct red-shifted peaks were observed and assigned to the CIP and SSIP. The assignments are interpreted in the framework of the vibrational Stark effect (VSE) and are supported by (1) the solvent dependence of ion-pair populations, (2) the observation of a cryptand-separated sodium ion pair that mimics the formation of SSIPs, and (3) electronic structure calculations. In the second part of this work, we show that a blue-shift of the nu(C=N) IR band due to the VSE can be induced in a nitrile-substituted fluorene radical anion by covalently tethering it to a metal-chelating ligand that forms an intramolecular ion pair upon reduction and complexation with sodium ion. This adds support to the conclusion that the shift in IR absorptions by ion pairing originates from the VSE. These results combined show that we can identify ion-pair structures by using the VSE, including the existence of SSIPs in a low-polarity solvent. PMID- 26807493 TI - Veliparib for the treatment of ovarian cancer. AB - INTRODUCTION: Ovarian cancer represents the sixth most commonly diagnosed cancer among women, with an incidence of 6.1 cases per 100.000 women and a cumulative lifetime risk of 0.5%. Treatment is based on debulking surgery and platinum-based chemotherapy, with the potential combination with taxane. However, the recently available data on the genetic basis and aetiology of ovarian cancer has led to the development of new anticancer drugs. Poly(ADP-ribose) polymerase (PARP) inhibitors are one of the most promising new classes of targeted agents currently under investigation for the treatment of ovarian cancer. Veliparib is a small molecule that inhibits both PARP-1 and PARP-2 and was originally shown to be efficacious in BRCA-associated tumors. AREAS COVERED: This manuscript reviews the Phase I and II studies investigating the use of veliparib in ovarian cancer. This article also provides and discusses the pharmacokinetics and pharmacodynamics of veliparib. EXPERT OPINION: It is still being discussed whether PARP inhibitors should be used in a front-line or relapsed setting, alone or in combination with cytotoxic chemotherapy or as maintenance treatment. In terms of veliparib, further investigations are needed to explore its full potential in ovarian cancer. It is hoped that the ongoing phase 3 trials will help to further elucidate it potential as a treatment option. PMID- 26807494 TI - Assessing disease activity in psoriasis and psoriatic arthritis: impact on management and therapy. AB - The management of psoriatic arthritis (PsA) and psoriasis has undergone major advancements over the last decade. This has been made possible, in part, due to the introduction of new therapies for their management, as well as global collaboration in the development of outcome measures and "treat- to- target" paradigms. In this review article, we discuss how disease activity is measured and the outcome measures that have been recently developed for the management of PsA. The importance of assessing the individual domains as well as global assessments both from the physician and patient perspective, and the development of composite measures are discussed. The newer PsA specific measures are expected to be more commonly used in clinical trials as well as clinical practice. PMID- 26807495 TI - NEAR-INFRARED AUTOFLUORESCENCE IN BILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION ASSOCIATED WITH ESOPHAGEAL CARCINOMA AND CHOROIDAL METASTASIS. AB - PURPOSE: To investigate the advantage of near-infrared autofluorescence (787 nm) for the detection of melanocytic lesions in a patient with bilateral diffuse uveal melanocytic proliferation in association with esophageal carcinoma complicated by most likely unilateral choroidal metastasis. METHODS: In this retrospective case report, a 55-year-old woman referred for the evaluation of sudden visual loss underwent normal ophthalmological evaluation and, in addition, was examined with near-infrared reflectance, near-infrared autofluorescence, fundus autofluorescence (Heidelberg Retina Angiograph II [HRA2; Heidelberg Engineering]), spectral domain optical coherence tomography (Spectralis OCT; Heidelberg Engineering), and multifocal electroretinography (RetiScan; Roland Consult). RESULTS: The patient had been diagnosed with esophageal carcinoma 3 months before the onset of visual symptoms. The visual acuity was 20/40 in the right eye and 20/20 in the left eye. Bilateral patchy melanocytic proliferation was detected on ophthalmoscopy. The extent of lesions was best detected with near infrared reflectance and near-infrared autofluorescence, whereas fundus autofluorescence and spectral domain optical coherence tomography did not reveal alterations of the outer retina or retinal pigment epithelium in this early stage of bilateral diffuse uveal melanocytic proliferation. The right eye showed in addition to the findings on the left eye choroidal folds in the fovea and an elevated lesion inferotemporal of the fovea suspicious of a choroidal metastasis. In the B-scan ultrasonography, a homogenous lesion was seen. Spectral domain optical coherence tomography demonstrated a mild accumulation of subretinal fluid adjacent to and over the choroidal metastasis. Transretinal biopsy of this elevated lesion revealed a low differentiated carcinoma of squamous epithelium, compatible with choroidal metastasis of the esophageal carcinoma. The choroidal metastasis increased within 3 months after the first visit. The visual acuity dropped in both eyes. The patient died 6 months after her first visit. CONCLUSIONS: Bilateral diffuse uveal melanocytic proliferation can be associated with esophageal carcinoma as a systemic malignancy. Near-infrared imaging can be helpful to detect early stages of BDUMP and can help offer recently reported treatment options at an early stage of disease. PMID- 26807497 TI - OCULAR INVOLVEMENT IN HEMOPHAGOCYTIC SYNDROME: A NOVEL FUNDUSCOPIC MANIFESTATION AND REVIEW OF THE LITERATURE. AB - PURPOSE: Hemophagocytic syndrome (HS) is a rare disease with a spectrum of ocular findings. The authors report a unique funduscopic presentation of HS in a neonate and a discussion of diagnosis, typical features, management, and outcome. METHODS: Single case report with retrospective analysis of the published literature of patients with HS and ocular findings from 1950 to present using the key terms hemophagocytic, lymphohistiocytosis, ocular, and ophthalmic. Literature search from 1950 to the present was performed through PubMed/MEDLINE and the Cochrane database. Requirement for inclusion was that the article or abstract was written in English. RESULTS: A 4-week-old neonate with HS demonstrated bilateral discrete white dots within the retina, which resolved incompletely over the course of the next months but showed increased pigmentation. CONCLUSION: With so few documented ophthalmic cases of HS in existence, the ocular findings at this point can be seen as diverse and variable. However as more cases are reported, hopefully this will allow for increased recognition of the ophthalmic manifestations and sequelae and in turn lead to improved treatment of this disease. PMID- 26807496 TI - SPONTANEOUS REGRESSION OF SEROUS RETINAL DETACHMENT ASSOCIATED WITH CIRCUMSCRIBED CHOROIDAL HEMANGIOMA AFTER CHILDBIRTH. AB - PURPOSE: To report a case of circumscribed choroidal hemangioma complicated by retinal detachment and regressed spontaneously after childbirth. METHODS: Clinical examination, fundus photography, spectral domain optical coherence tomography with enhanced depth imaging, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and microperimetry. RESULTS: A 41 year-old woman was referred with a 2-week history of decreased vision and scotoma in the left eye. She was in her sixth month of pregnancy. Fundus examination revealed a circumscribed choroidal hemangioma appearing as a solitary orange-red mass in the upper peripapillary area and neurosensory retinal detachment of the macula. After the birth, spontaneous regression of the retinal detachment was observed. CONCLUSION: Pregnancy may cause exacerbation of choroidal hemangioma, and regression of the exudation may occur spontaneously after delivery. Treatment is not indicated when symptoms or signs of exudation disappear. PMID- 26807498 TI - Role of vertical transmission of Toxoplasma gondii in prevalence of infection. AB - The parasite, Toxoplasma gondii, is a highly successful pathogen that infects around 30% of the global human population. Additionally, it is able to infect all warm blooded animals with high prevalence. This is surprising as it is a parasite of the cat and can only complete its full sexual cycle in that host. This review examines the important key routes of transmission: infective oocysts from the cat, ingestion of raw infected tissue and vertical transmission. The latter route of transmission has traditionally been thought to be rare. In this review, this assumption is examined and discussed in the light of the current literature. The available evidence points to the possibility that vertical transmission occurs frequently in natural populations of mice however the evidence in sheep is currently ambivalent and controversial. In humans, the situation appears as though vertical transmission may be rare although there is still much that is unexplained. PMID- 26807499 TI - Increased p53 and decreased p21 accompany apoptosis induced by ultraviolet radiation in the nervous system of a crustacean. AB - Ultraviolet (UV) radiation can produce biological damage, leading the cell to apoptosis by the p53 pathway. This study evaluated some molecular markers of the apoptosis pathway induced by UVA, UVB and UVA+ UVB (Solar Simulator, SIM) in environmental doses, during five consecutive days of exposure, in the brain of the crab Ucides cordatus. We evaluated the central nervous system (CNS) by immunoblotting the content of proteins p53, p21, phosphorylated AKT, BDNF, GDNF, activated caspase-3 (C3) and phosphohistone H3 (PH3); and by immunohistochemical tests of the cells labeled for PH3 and C3. After the fifth day of exposure, UVB radiation and SIM increased the protein content of p53, increasing the content of AKT and, somehow, blocking p21, increasing the content of activated caspase-3, which led the cells to apoptosis. The signs of death affected the increase in neurotrophins, such as BDNF and GDNF, stimulating the apoptotic cascade of events. Immunohistochemical assays and immunoblotting showed that apoptosis was present in the brains of all UV groups, while the number of mitotic cells in the same groups decreased. In conclusion, environmental doses of UV can cause apoptosis by increasing p53 and decreasing p21, revealing an UV-damage pathway for U. cordatus. PMID- 26807500 TI - Visual input signaling threat gains preferential access to awareness in a breaking continuous flash suppression paradigm. AB - Visual input that signals threat is inherently relevant for survival. Accordingly, it has been demonstrated that threatening visual input elicits faster behavioral responses than non-threatening visual input. Considering that awareness is a prerequisite for performing demanding tasks and guiding novel behavior, we hypothesized that threatening visual input would gain faster access to awareness than non-threatening visual input. In the present study, we associated one of two basic visual stimuli, that were devoid of intrinsic relevance (colored annuli), with aversive stimulation (i.e., electric shocks) following a classical fear conditioning procedure. In the subsequent test phase no more electric shocks were delivered, and a breaking continuous flash suppression task was used to measure how fast these stimuli would access awareness. The results reveal that stimuli that were previously paired with an electric shock break through suppression faster than comparable stimuli that were not paired with an electric shock. PMID- 26807501 TI - Stimulation over primary motor cortex during action observation impairs effector recognition. AB - Recent work suggests that motor cortical processing during action observation plays a role in later recognition of the object involved in the action. Here, we investigated whether recognition of the effector making an action is also impaired when transcranial magnetic stimulation (TMS) - thought to interfere with normal cortical activity - is applied over the primary motor cortex (M1) during action observation. In two experiments, single-pulse TMS was delivered over the hand area of M1 while participants watched short clips of hand actions. Participants were then asked whether an image (experiment 1) or a video (experiment 2) of a hand presented later in the trial was the same or different to the hand in the preceding video. In Experiment 1, we found that participants' ability to recognise static images of hands was significantly impaired when TMS was delivered over M1 during action observation, compared to when no TMS was delivered, or when stimulation was applied over the vertex. Conversely, stimulation over M1 did not affect recognition of dot configurations, or recognition of hands that were previously presented as static images (rather than action movie clips) with no object. In Experiment 2, we found that effector recognition was impaired when stimulation was applied part way through (300ms) and at the end (500ms) of the action observation period, indicating that 200ms of action-viewing following stimulation was not long enough to form a new representation that could be used for later recognition. The findings of both experiments suggest that interfering with cortical motor activity during action observation impairs subsequent recognition of the effector involved in the action, which complements previous findings of motor system involvement in object memory. This work provides some of the first evidence that motor processing during action observation is involved in forming representations of the effector that are useful beyond the action observation period. PMID- 26807503 TI - Characterization of Soybean Storage and Allergen Proteins Affected by Environmental and Genetic Factors. AB - There is limited information on the influence of genetic and environmental variability on soybean protein composition. This study aimed to determine the role of genotype (G), environments (E), and the interrelationship of genotype and environment (G*E) on soybean seed protein. Three sets of nine soybean genotypes were grown in replicated trials at Maryland, South Carolina, and South Dakota. At each location, the nine genotypes were grown with two planting/sowing dates. We applied two-dimensional gel electrophoresis and mass spectrometry to study the variability of soybean storage and allergen proteins. Statistical analysis of 47 storage and 8 allergen proteins, in terms of differentially expressed protein spots significant at the p<0.005 level, was performed. We found more spots that showed statistically significant differences in expression among E compared to G and G*E interaction. PMID- 26807504 TI - Multifrequency force microscopy using flexural and torsional modes by photothermal excitation in liquid: atomic resolution imaging of calcite (1014). AB - We introduce a new multifrequency atomic force microscopy (AFM) method which involves the excitation of flexural and torsional eigenmodes of the microcantilever probe in liquid environments. The flexural and torsional deflection signals are mostly decoupled in the majority of commercial AFM setups, so they can be relatively easily recorded and processed. The use of torsional modes provides additional surface information at the atomic scale, with respect to flexural mode imaging alone, although the flexural modes are the only ones capable of 'true' atomic resolution imaging. In our experiments, the torsional modes are shown to be particularly sensitive to protruding oxygen surface atoms on the calcite (1014) plane. The high lateral resolution capability of the flexural modes, combined with the high sensitivity of the torsional modes to specific surface features in liquid environments, can thus offer the means of observing chemical contrast at the atomic level using purely mechanical measurement AFM techniques, even in the absence of tip functionalization. PMID- 26807502 TI - Short term omega-3 polyunsaturated fatty acid supplementation induces favorable changes in right ventricle function and diastolic filling pressure in patients with chronic heart failure; A randomized clinical trial. AB - INTRODUCTION: Omega-3 polyunsaturated fatty acids (omega 3-PUFAs) seem to favorably affect cardiac hemodynamics and may benefit the clinical course of heart failure patients. The role of omega 3-PUFAs supplementation on the left and right ventricular function of patients with chronic compensated systolic heart failure, under optimal treatment, was studied. METHODS: 205 consecutive patients with chronic compensated heart failure, due to ischemic (IHF) or dilated cardiomyopathy (DCM)-NYHA classification I-III, under optimal medical treatment, were enrolled. Participants were 1-to-1 randomized on 1000 mg omega 3-PUFA supplementation or no supplementation, in a non-blinded fashion. Echocardiographic assessment was performed at first visit and 6 months after. Plasma BNP and serum creatinine levels were also measured. RESULTS: As compared with the control group, BNP levels in omega 3-PUFA intervention group were 34.6% lower (p=0.001); end-diastolic and end-systolic left ventricle dimensions were decreased by 2.5% (p=0.047) and 3.7% (p=0.01), maximum diameter of left atrium was decreased by 8.4% (p=0.004), left atrium ejection fraction was ameliorated by 6.03% (p=0.021) and as regards tissue Doppler parameters, TDI_Etv/Atv was decreased in omega 3-PUFA intervention group by 6.3% (p=0.038). Moreover, improvement in diastolic indices was more prominent in subjects with DCM as compared to IHF patients. CONCLUSION: Omega 3-PUFA supplementation was associated with improved left diastolic function and decreased BNP levels in patients with chronic heart failure. These findings suggest a beneficial role of omega 3-PUFAs on the hemodynamic course of patients with systolic heart failure. PMID- 26807505 TI - Psychosocial Profile of Children Having Participated in an Intervention Program for Their Sexual Behavior Problems: The Predictor Role of Maltreatment. AB - This study sought to verify if a history of maltreatment may predict the psychosocial profile of children who participated in an intervention program aiming at reducing sexual behavior problems. Data were collected at both the beginning and the end of the intervention program using a clinical protocol and standardized tests selected on the basis of the intervention targets. In general, the results indicate that children who had experienced maltreatment display a psychosocial profile that is similar to that of children who had not experienced maltreatment. However, children who had experienced psychological abuse or neglect may display greater externalized or sexualized behaviors, whereas children who have a parent who had been a victim of sexual abuse may display fewer sexualized behaviors. PMID- 26807506 TI - Fluorination Induced the Surface Segregation of High Voltage Spinel on Lithium Rich Layered Cathodes for Enhanced Rate Capability in Lithium Ion Batteries. AB - This study is aimed to explore the effect of fluoride doping and the associated structural transformation on lithium-rich layered cathode materials. The polymeric fluoride source is first adopted for synthesizing lithium intercalated oxide through a newly developed organic precipitation process. A heterostructured spinel/layered composite cathode material is obtained after appreciable fluorination and a superior rate capability is successfully achieved. The fluoride dopant amount and the surface spinel phase are evidenced and systematically examined by various structural spectroscopy and electrochemical analysis. It appears the reversible Ni(2+/4+) redox couple at high voltage regime around 4.8 V because of the formation of spinel LiNi1/2Mn3/2O4 phase. The mechanism of "layer to spinel" phase transformation is discussed in detail. PMID- 26807507 TI - Physician perceptions of GLP-1 receptor agonists in the UK. AB - Objectives Glucagon-like peptide-1 (GLP-1) receptor agonists have been used to treat type 2 diabetes for almost a decade, and new treatments in this class have recently been introduced. The purpose of this study was to examine perceptions of GLP-1 receptor agonists among physicians who treat patients with type 2 diabetes in the UK. Methods A total of 670 physicians (226 diabetes specialists; 444 general practice [GP] physicians) completed a survey in 2014. Results Almost all physicians had prescribed GLP-1 receptor agonists (95.4% total sample; 99.1% specialists; 93.5% GP), most frequently to patients whose glucose levels are not adequately controlled with oral medications (85.9% of physicians) and obese/overweight patients (83.7%). Physicians' most common reasons for prescribing a GLP-1 receptor agonist were: associated with weight loss (65.8%), good efficacy (55.7%), less hypoglycemia risk than insulin (55.2%), not associated with weight gain (34.5%), and better efficacy than oral medications (32.7%). Factors that most commonly cause hesitation when prescribing this class were: not considered first line therapy according to guidelines (56.9%), injectable administration (44.6%), cost (36.7%), gastrointestinal side effects (33.4%), and risk of pancreatitis (26.7%). Almost all specialists (99.1%) believed they had sufficient knowledge to prescribe a GLP-1 receptor agonist, compared with 76.1% of GPs. Conclusions Results highlight the widespread use of GLP-1 receptor agonists for treatment of type 2 diabetes in the UK. However, almost a quarter of GPs reported that they do not have enough knowledge to prescribe GLP-1s, suggesting a need for increased dissemination of information to targeted groups of physicians. Study limitations were that the generalizability of the clinician sample is unknown; survey questions required clinicians to select answers from multiple response options rather than generating the responses themselves; and responses to this survey conducted in 2014 do not reflect perceptions of the most recently introduced GLP-1 receptor agonists. PMID- 26807508 TI - Impaired Antiviral Stress Granule and IFN-beta Enhanceosome Formation Enhances Susceptibility to Influenza Infection in Chronic Obstructive Pulmonary Disease Epithelium. AB - Chronic obstructive pulmonary disease (COPD) is a serious lung disease that progressively worsens lung function. Those affected are highly susceptible to influenza virus infections that result in exacerbations with exaggerated symptoms with increased mortality. The mechanisms underpinning this increased susceptibility to infection in COPD are unclear. In this study, we show that primary bronchial epithelial cells (pBECs) from subjects with COPD have impaired induction of type I IFN (IFN-beta) and lead to heightened viral replication after influenza viral infection. COPD pBECs have reduced protein levels of protein kinase (PK) R and decreased formation of PKR-mediated antiviral stress granules, which are critical in initiating type I IFN inductions. In addition, reduced protein expression of p300 resulted in decreased activation of IFN regulatory factor 3 and subsequent formation of IFN-beta enhanceosome in COPD pBECs. The decreased p300 induction was the result of enhanced levels of microRNA (miR)-132. Ectopic expression of PKR or miR-132 antagomiR alone failed to restore IFN-beta induction, whereas cotreatment increased antiviral stress granule formation, induction of p300, and IFN-beta in COPD pBECs. This study reveals that decreased induction of both PKR and p300 proteins contribute to impaired induction of IFN beta in COPD pBECs upon influenza infection. PMID- 26807509 TI - Hepatic adenylate cyclase 3 is upregulated by Liraglutide and subsequently plays a protective role in insulin resistance and obesity. AB - OBJECTIVE: Recent studies have demonstrated that adenylate cyclase 3 (AC3) has a protective role in obesity. This gene resides at the pathway with glucagon-like peptide (GLP)-1. Liraglutide is a GLP-1 analog and has independent glucose and body weight (BW)-reducing effects. In the present study, we aimed to examine whether hepatic AC3 activity was regulated by Liraglutide and to further understand the effect of AC3 in reduction of BW and insulin resistance. SUBJECTS: The diabesity and obese mice were induced from db/db and C57BL/6 J mice, respectively, by high-fat diet. Liraglutide (0.1 mg kg(-1) per 12 h) was given to the mice twice daily for 12 weeks. C57BL/6 J mice fed with chow diet and obese or diabesity mice treated with saline were used as the controls. Hepatic AC3 gene expression at mRNA and protein levels was analyzed with real-time reverse transcription-PCR and western blot. Fasting blood glucose and serum insulin levels were measured and followed insulin resistance index (HOMA-IR) was evaluated according to the homeostasis model assessment. RESULTS: After administration of Liraglutide, BW and HOMA-IR in obese and diabesity mice were decreased, whereas hepatic AC3 mRNA and protein expression levels were upregulated. The AC3 gene expression was negatively correlated with BW, HOMA-IR and the area ratio of hepatic fat deposition in the liver. CONCLUSIONS: The present study thus provides the evidence that hepatic AC3 gene expression is upregulated by Liraglutide. The reduction of BW and improvement of insulin resistance with Liraglutide may be partially explained by AC3 activation. PMID- 26807510 TI - Serum S-adenosylmethionine, but not methionine, increases in response to overfeeding in humans. AB - BACKGROUND: Plasma concentration of the methyl donor S-adenosylmethionine (SAM) is linearly associated with body mass index (BMI) and fat mass. As SAM is a high energy compound and a sensor of cellular nutrient status, we hypothesized that SAM would increase with overfeeding. METHODS: Forty normal to overweight men and women were overfed by 1250 kcal per day for 28 days. RESULTS: Serum SAM increased from 106 to 130 nmol/l (P=0.006). In stratified analysis, only those with weight gain above the median (high-weight gainers; average weight gain 3.9+/-0.3 kg) had increased SAM (+42%, P=0.001), whereas low-weight gainers (weight gain 1.5+/-0.2 kg) did not (Pinteraction=0.018). Overfeeding did not alter serum concentrations of the SAM precursor, methionine or the products, S-adenosyl-homocysteine and homocysteine. The SAM/SAH (S-adenosylhomocysteine) ratio was unchanged in the total population, but increased in high-weight gainers (+52%, P=0.006, Pinteraction =0.005). Change in SAM correlated positively with change in weight (r=0.33, P=0.041) and fat mass (r=0.44, P=0.009), but not with change in protein intake or plasma methionine, glucose, insulin or low-density lipoprotein (LDL) cholesterol. CONCLUSION: Overfeeding raised serum SAM in proportion to the fat mass gained. The increase in SAM may help stabilize methionine levels, and denotes a responsiveness of SAM to nutrient state in humans. The role of SAM in human energy metabolism deserves further attention. PMID- 26807511 TI - A systematic comparison of sugar content in low-fat vs regular versions of food. AB - Obesity remains a significant public health concern. One of the primary messages from providers and health-care organizations is to eat healthier foods with lower fat. Many in the lay press, however, have suggested that lower fat versions of foods contain more sugar. To our knowledge, a systematic comparison of the sugar content in food with lower fat alternatives has not been performed. In this study, we compared fat free, low fat and regular versions of the same foods using data collected from the USDA National Nutrient Database. We found that the amount of sugar is higher in the low fat (that is, reduced calorie, light, low fat) and non-fat than 'regular' versions of tested items (Friedman P=0.00001, Wilcoxon P=0.0002 for low fat vs regular food and P=0.0003 for non-fat vs regular food). Our data support the general belief that food that is lower in fat may contain more sugar. PMID- 26807513 TI - Hepatocellular cancer as indication for liver transplantation: pushing beyond Milan. AB - PURPOSE OF REVIEW: The Milan criteria have been considered the gold standard for the selection of patients with hepatocellular cancer (HCC) for liver transplantation. However, there is growing evidence that tumor burden is just one of many factors that predict HCC recurrence after liver transplantation. RECENT FINDINGS: Modest expansion beyond Milan criteria, including the University of California, San Francisco and up-to-7 criteria, appear to yield acceptable posttransplantation outcomes, but their implementation should achieve a minimal survival threshold to not harm non-HCC patients awaiting liver transplantation. Down-staging of HCC patients into Milan criteria appears to produce excellent posttransplant outcomes similar to those always within Milan criteria. Incorporating alpha-fetoprotein into the selection scheme may further improve posttransplant outcome. Response to local regional therapy (LRT) may help identify candidates who would do well after liver transplantation even if their initial tumor burden exceeds Milan criteria. Conversely, tumor progression despite LRT is a poor prognostic factor for tumors within or beyond Milan criteria. Under the 'ablate and wait' principle, a sufficient length of time to observe tumor behavior is essential to avoid transplanting those with aggressive tumors too quickly, as these patients would likely do poorly after liver transplantation. SUMMARY: Tumor size and number tell only a partial tale of the characteristics that predict posttransplant outcomes. To this end, successful down-staging appears to carry equivalent posttransplantation outcomes to those always within Milan criteria. Accounting for tumor biology with alpha-fetoprotein and response to LRT as well as assessing modifiable risk factors such as wait time is crucial to improve selection criteria and improve posttransplantation outcomes. PMID- 26807512 TI - Isolation of a Novel Insect-Specific Flavivirus from Culiseta melanura in the Northeastern United States. AB - The genus Flavivirus includes a number of newly recognized viruses that infect and replicate only within mosquitoes. To determine whether insect-specific flaviviruses (ISFs) may infect Culiseta (Cs.) melanura mosquitoes, we screened pools of field-collected mosquitoes for virus infection by RT-PCR targeting conserved regions of the NS5 gene. NS5 nucleotide sequences amplified from Cs. melanura pools were genetically similar to other ISFs and most closely matched Calbertado virus from Culex tarsalis, sharing 68.7% nucleotide and 76.1% amino acid sequence identity. The complete genome of one virus isolate was sequenced to reveal a primary open reading frame (ORF) encoding a viral polyprotein characteristic of the genus Flavivirus. Phylogenetic analysis showed that this virus represents a distinct evolutionary lineage that belongs to the classical ISF group. The virus was detected solely in Cs. melanura pools, occurred in sampled populations from Connecticut, New York, New Hampshire, and Maine, and infected both adult and larval stages of the mosquito. Maximum likelihood estimate infection rates (MLE-IR) were relatively stable in overwintering Cs. melanura larvae collected monthly from November of 2012 through May of 2013 (MLE IR = 0.7-2.1/100 mosquitoes) and in host-seeking females collected weekly from June through October of 2013 (MLE-IR = 3.8-11.5/100 mosquitoes). Phylogenetic analysis of viral sequences revealed limited genetic variation that lacked obvious geographic structure among strains in the northeastern United States. This new virus is provisionally named Culiseta flavivirus on the basis of its host association with Cs. melanura. PMID- 26807514 TI - Life cycle assessment of lignocellulosic ethanol: a review of key factors and methods affecting calculated GHG emissions and energy use. AB - Lignocellulosic ethanol has potential for lower life cycle greenhouse gas emissions compared to gasoline and conventional grain-based ethanol. Ethanol production 'pathways' need to meet economic and environmental goals. Numerous life cycle assessments of lignocellulosic ethanol have been published over the last 15 years, but gaps remain in understanding life cycle performance due to insufficient data, and model and methodological issues. We highlight key aspects of these issues, drawing on literature and a case study of corn stover ethanol. Challenges include the complexity of feedstock/ecosystems and market-mediated aspects and the short history of commercial lignocellulosic ethanol facilities, which collectively have led to uncertainty in GHG emissions estimates, and to debates on LCA methods and the role of uncertainty in decision making. PMID- 26807515 TI - Histologic and Phenotypic Factors and MC1R Status Associated with BRAF(V600E), BRAF(V600K), and NRAS Mutations in a Community-Based Sample of 414 Cutaneous Melanomas. AB - Cutaneous melanomas arise through causal pathways involving interplay between exposure to UV radiation and host factors, resulting in characteristic patterns of driver mutations in BRAF, NRAS, and other genes. To gain clearer insights into the factors contributing to somatic mutation genotypes in melanoma, we collected clinical and epidemiologic data, performed skin examinations, and collected saliva and tumor samples from a community-based series of 414 patients aged 18 to 79, newly diagnosed with cutaneous melanoma. We assessed constitutional DNA for nine common polymorphisms in melanocortin-1 receptor gene (MC1R). Tumor DNA was assessed for somatic mutations in 25 different genes. We observed mutually exclusive mutations in BRAF(V600E) (26%), BRAF(V600K) (8%), BRAF(other) (5%), and NRAS (9%). Compared to patients with BRAF wild-type melanomas, those with BRAF(V600E) mutants were significantly younger, had more nevi but fewer actinic keratoses, were more likely to report a family history of melanoma, and had tumors that were more likely to harbor neval remnants. BRAF(V600K) mutations were also associated with high nevus counts. Both BRAF(V600K) and NRAS mutants were associated with older age but not with high sun exposure. We also found no association between MC1R status and any somatic mutations in this community sample of cutaneous melanomas, contrary to earlier reports. PMID- 26807516 TI - Increased, but Functionally Impaired, CD14(+) HLA-DR(-/low) Myeloid-Derived Suppressor Cells in Psoriasis: A Mechanism of Dysregulated T Cells. AB - The clinical extent of psoriasis pathology is regulated in part by defects in immune networks, including a defect in the suppressive actions of regulatory T cells. Recently, CD14(+) HLA-DR(-/low) monocytic myeloid-derived suppressor cells (Mo-MDSCs) have been shown to suppress T-cell activation as one of their suppressive mechanisms. However, little is known about the role of Mo-MDSCs and their functional relationship to T-cell suppression in relation to human chronic immune-mediated inflammatory diseases, including psoriasis. Despite psoriasis being a hyperinflammatory condition, Mo-MDSCs were elevated in psoriatic patient peripheral blood mononuclear cells compared to nonpsoriatic healthy controls (2.6% vs. 0.9%, P < 0.002). Freshly isolated psoriatic Mo-MDSCs directly suppressed CD8 T-cell proliferation less efficiently than healthy control Mo MDSCs. In addition, psoriatic Mo-MDSCs expressed reduced surface expression of programmed cell death protein 1 compared to healthy controls. Additional in vitro assays also demonstrated that psoriatic and control Mo-MDSCs both induce regulatory T-cell conversion from naive T effector cells, but, importantly, the regulatory T cells induced by psoriatic Mo-MDSCs displayed decreased suppressive functionality. These results suggest that aberrations in psoriatic Mo-MDSCs prevent proper suppression of effector T-cell expansion and hamper the immune system's ability to correctly self-regulate. PMID- 26807517 TI - DNA methyltransferase detection based on digestion triggering the combination of poly adenine DNA with gold nanoparticles. AB - DNA methyltransferase (MTase) has received a large amount of attention due to its catalyzation of DNA methylation in both eukaryotes and prokaryotes, which has a close relationship to cancer and bacterial diseases. Herein, a novel electrochemical strategy based on Dpn I digestion triggering the combination of poly adenine (polyA) DNA with a gold nanoparticles functioned glassy carbon electrode (AuNPs/GCE), is developed for the simple and efficient detection of DNA MTase and inhibitor screening. Only one methylene blue (MB)-labeled DNA hairpin probe and two enzymes are involved in this designed method. In the presence of Dam MTase, the hairpin probe can be methylated and then cleaved by the restriction endonuclease. Thus, a MB-labeled polyA signal-stranded DNA product is introduced to the surface of AuNPs/GCE through the effect between polyA and AuNPs, resulting in an obvious electrochemical signal. On the contrary, in the absence of Dam MTase, the DNA probe cannot be cleaved and a relatively small electrochemical response can be observed. As a result, the as-proposed biosensor offered an efficient way for Dam MTase activity monitoring with a low detection of 0.27 U/mL, a wide linear range and good stability. Additionally, this assay holds great potential for further application in real biological matrices and inhibitors screening, which is expected to be useful in disease diagnosis and drug discovery. PMID- 26807518 TI - Paper-based fluorescence resonance energy transfer assay for directly detecting nucleic acids and proteins. AB - Paper-based fluorescence resonance energy transfer assay (FRET) is gaining great interest in detecting macro-biological molecule. It is difficult to achieve conveniently and fast detection for macro-biological molecule. Herein, a graphene oxide (GO)-based paper chip (glass fiber) integrated with fluorescence labeled single-stranded DNA (ssDNA) for fast, inexpensive and direct detection of biological macromolecules (proteins and nucleic acids) has been developed. In this paper, we employed the Cy3/FAM-labeled ssDNA as the reporter and the GO as quencher and the original glass fiber paper as data acquisition substrates. The chip which was designed and fabricated by a cutting machine is a miniature biosensor that monitors fluorescence recovery from resonance energy transfer. The hybridization assays and fluorescence detection were all simplified, and the surface of the chip did not require immobilization or washing. A Nikon Eclipse was employed as excited resource and a commercial digital camera was employed for capturing digital images. This paper-based microfluidics chip has been applied in the detection of proteins and nucleic acids. The biosensing capability meets many potential requirements for disease diagnosis and biological analysis. PMID- 26807519 TI - Modified nanoporous titanium dioxide as a novel carrier for enzyme immobilization. AB - epsilon-Poly-L-lysine (EPL)-modified mesoporous titanium dioxide (M-TiO2) was assembled through the electrostatic attraction between EPL and M-TiO2. Through modification, the M-TiO2 surface tends to form multilayered and complex architectures, which can be used as artificial matrices to change the microenvironment of carriers for enzyme immobilization. The modified M-TiO2 was characterized through scanning electron microscopy, Fourier transform infrared spectroscopy, zeta potential analysis, and thermogravimetric analysis. All of the immobilized enzymes with negative charges display strong storage stability, thermal stability, and good reusability. Results indicate that EPL can self assemble onto the surface of M-TiO2 and form a considerable number of active coatings. Our results also demonstrate that this simple and novel method can be potentially used to immobilize negatively charged enzymes for biosensor applications. PMID- 26807520 TI - Isothermal RNA detection through the formation of DNA concatemers containing HRP mimicking DNAzymes on the surface of gold nanoparticles. AB - An enzyme-free signal amplification strategy for colorimetric detection of RNA molecules was developed. The detecting process was started by the hybridization of the target RNA via two helper oligonucleotides to bi-functionalized (initiator and linker oligonucleotides-modified) gold nanoparticles. Afterwards, in presence of two auxiliary oligonucleotides, the nanoparticle-confined initiators triggered the formation of DNA concatemers containing hemin-binding aptamers through a modified hybridization chain reaction [HCR] strategy. In addition to the mediatory role, the helper oligonucleotides, with a toehold-mediated strand displacement [TMSD] ability, helped unwind the secondary structures of the RNA molecule and provided a binding site for a biotinylated capture probe. Upon binding, the complex was harvested on the streptavidin-coated microwell, and subsequently the formation of HRP-mimicking DNAzymes was stimulated by adding hemin molecules. The assay was successfully employed for detecting target nucleic acids, which bears secondary structures, in isothermal conditions (room temperature) without heat denaturation. The assay detected DNA molecule with LOD value of 1 pM with the ability to differentiate a spurious target containing a single-nucleotide substitution. On real RNA samples, the assay truly discriminated Escherichia coli O157:H7's 16s rRNA from closely related bacteria with a detection limit of >= 5 * 10(5)CFU. Compared to enzyme-based signal amplifications, the assay can detect the target RNA with a sensitivity similar to the one already found for RT-PCR, NASBA, and RT-LAMP assays. Overall, the analytical platform eliminates the need for enzymatic reactions, heat denaturation, and complicated instruments during the detection process. PMID- 26807521 TI - Low-fouling surface plasmon resonance biosensor for multi-step detection of foodborne bacterial pathogens in complex food samples. AB - Recent outbreaks of foodborne illnesses have shown that foodborne bacterial pathogens present a significant threat to public health, resulting in an increased need for technologies capable of fast and reliable screening of food commodities. The optimal method of pathogen detection in foods should: (i) be rapid, specific, and sensitive; (ii) require minimum sample preparation; and (iii) be robust and cost-effective, thus enabling use in the field. Here we report the use of a SPR biosensor based on ultra-low fouling and functionalizable poly(carboxybetaine acrylamide) (pCBAA) brushes for the rapid and sensitive detection of bacterial pathogens in crude food samples utilizing a three-step detection assay. We studied both the surface resistance to fouling and the functional capabilities of these brushes with respect to each step of the assay, namely: (I) incubation of the sensor with crude food samples, resulting in the capture of bacteria by antibodies immobilized to the pCBAA coating, (II) binding of secondary biotinylated antibody (Ab2) to previously captured bacteria, and (III) binding of streptavidin-coated gold nanoparticles to the biotinylated Ab2 in order to enhance the sensor response. We also investigated the effects of the brush thickness on the biorecognition capabilities of the gold-grafted functionalized pCBAA coatings. We demonstrate that pCBAA-compared to standard low fouling OEG-based alkanethiolate self-assemabled monolayers-exhibits superior surface resistance regarding both fouling from complex food samples as well as the non-specific binding of S-AuNPs. We further demonstrate that a SPR biosensor based on a pCBAA brush with a thickness as low as 20 nm was capable of detecting E. coli O157:H7 and Salmonella sp. in complex hamburger and cucumber samples with extraordinary sensitivity and specificity. The limits of detection for the two bacteria in cucumber and hamburger extracts were determined to be 57 CFU/mL and 17 CFU/mL for E. coli and 7.4 * 10(3) CFU/mL and 11.7 * 10(3)CFU/mL for Salmonella sp., respectively. In addition, we demonstrate the simultaneous detection of E. coli and Salmonella sp. in hamburger sample using a multichannel SPR biosensor having appropriate functional coatings. PMID- 26807522 TI - Cyclic up-regulation fluorescence of pyrene excimer for studying polynucleotide kinase activity based on dual amplification. AB - Due to its important biological and clinical roles of polynucleotide kinase (PNK), accurate monitoring of PNK activity and inhibition is highly desirable. Herein, a homogeneous and sensitive fluorescence assay has been proposed for the detection of PNK activity by integrating target recycling signal amplification of DNA toehold strand displacement reaction (TSDR) with gamma-cyclodextrin (gamma CD) enhancement of pyrene excimer. A label-free hairpin DNA1 (H1) and two singly pyrene-labelled DNA, H2 and H3, are designed. Accompanying the occurrence of the efficient enzyme reactions, namely phosphorylation-actuated lambda exonuclease reaction, a single-stranded DNA as a trigger DNA (tDNA) of TSDR can be released from H1. Then, tDNA drives circulatory interactions between H2 and H3 to continuously form H2/H3 duplex, resulting in formation of pyrene excimer and a "turn on" fluorescence signal of pyrene excimer. Furthermore, the fluorescence of pyrene excimer is further amplified by introducing gamma-cyclodextrin (gamma-CD), which can regulate the space proximity of two pyrene molecules. Thus, TSDR induced cyclic formation of pyrene excimer and gamma-CD enhancement can specifically up-regulate the fluorescence of pyrene excimer for detection of PNK activity, the detection limit is 9.3 * 10(-5)UmL(-1), which is superior to those of most existing approaches. Moreover, the proposed strategy can also be successfully utilized to study inhibition efficiency of different PNK inhibitors as well. Therefore, a dual amplification approach is provided for nucleic acid phosphorylation related researches. PMID- 26807523 TI - A novel surface plasmon resonance biosensor for enzyme-free and highly sensitive detection of microRNA based on multi component nucleic acid enzyme (MNAzyme) mediated catalyzed hairpin assembly. AB - MicroRNAs (miRNAs) are potentially useful biomarkers for early diagnosis of human diseases. Here, a simple surface plasmon resonance (SPR) biosensor has been developed for highly sensitive detection of miRNA by designing a new enzyme-free and isothermal amplification strategy, named multi component nucleic acid enzyme mediated mismatched catalyzed hairpin assembly (MNAzyme-CHA). The partial MNAzymes co-recognized the target to form a stable active MNAzyme, which continued to digest multiple hairpin H0 substrates, concomitantly generating a lot of fragments. The H0 fragments could initiate the mismatched CHA cycles, resulting in the generation of massive hairpin H1-H2 complexes. As a result, the H1-H2 complexes and streptavidin were attached to the sensor surface, leading to a significantly amplified SPR signal readout. The established biosensor showed high sensitivity and selectivity with a wide dynamic range from 1 pM to 100 nM. It was also successfully applied to the determination of target miRNA spiked into human total RNA samples. Thus, this developed biosensing strategy presents a simple and stable platform toward sensitive and convenient miRNA detection, and has great potential in assays of many other nucleic acids analytes for biomedical research and early clinical diagnosis. PMID- 26807524 TI - Highly sensitive and selective electrochemical detection of Hg(2+) through surface-initiated enzymatic polymerization. AB - A Hg(2+) electrochemical biosensor is developed by integrating thymine-Hg(2+) thymine (T-Hg(2+)-T) base pairs for the high selectivity with surface-initiated enzymatic polymerization (SIEP) for signal amplification. The fabrication begins with the covalent conjugation of capture DNA probe labeled with thiol at its 3'terminal onto the gold electrode. The presence of Hg(2+) leads to DNA hybridization, in which complementary DNA was captured onto the biosensor surface, which subsequently catalyzed the addition of deoxynucleotides (dNTP) containing biotinlated 2'-deoxyadenosine 5'-triphosphate (biotin-dATP) by terminal deoxynucleotidyl transferase (TdT). The binding between biotin and strepavidin leads to the attachment of a large number of strepavidin functionalized silver nanoparticles (strepavidin-AgNPs), which could generate electrochemical stripping signal of silver to monitor the concentration of Hg(2+) in KCl solution. Through utilizing the T-Hg(2+)-T selectivity and SIEP amplification, this assay method can detect aqueous Hg(2+) with a wide linear range from 0.05 nM to 100 nM and a detection limit of 0.024 nM. The application of this sensor in the analysis of drinking water demonstrates that the proposed method works well for real samples. PMID- 26807525 TI - Enhancing sensitivity and selectivity in a label-free colorimetric sensor for detection of iron(II) ions with luminescent molybdenum disulfide nanosheet-based peroxidase mimetics. AB - In the present study, we demonstrated that the luminescent molybdenum disulfide (MoS2) nanosheets, which were prepared hydrothermally by using sodium molybdate and thiourea as precursors, possessed peroxidase-like activity, and could catalyze the oxidation of peroxidase substrate o-phenylenediamine (OPD) in the presence of hydrogen peroxide (H2O2) to produce a yellow color reaction. Further addition of Fe(2+) into the nanosheets led to peroxidase mimetics with greatly enhanced catalytic activity. The observation was exploited to develop a label free colorimetric nanozyme sensor for detection of Fe(2+). The fabricated MoS2/OPD/H2O2 sensor showed a wide linear range of 0.01-0.8 uM with a detection limit of 7 nM. Moreover, it was found that the MoS2/OPD/H2O2 sensor displayed enhanced sensitivity and selectivity toward Fe(2+) compared with the OPD/H2O2 sensor, suggesting that the MoS2 nanosheets could improve the performance of the Fe(2+) sensor. An advanced chemometrics algorithm, multivariate curve resolution by alternating least squares (MCR-ALS), was further applied to interpret the origin of enhancing sensitivity and selectivity in the Fe(2+) sensor with the MoS2 nanosheets. The time-dependent UV-vis spectral data of the studied systems were collected, and submitted to the MCR-ALS. The results showed that the increased sensitivity and selectivity of the MoS2/OPD/H2O2 sensor for Fe(2+) detection likely arose from its large reaction rate constant. Finally, the proposed MoS2/OPD/H2O2 sensor was successfully applied for detection of Fe(2+) in water samples. PMID- 26807526 TI - Enhanced hydrogen production in microbial electrolysis cell with 3D self-assembly nickel foam-graphene cathode. AB - In comparison to precious metal catalyst especially Platinum (Pt), nickel foam (NF) owned cheap cost and unique three-dimensional (3D) structure, however, it was scarcely applied as cathode material in microbial electrolysis cell (MEC) as the intrinsic laggard electrochemical activity for hydrogen recovery. In this study, a self-assembly 3D nickel foam-graphene (NF-G) cathode was fabricated by facile hydrothermal approach for hydrogen evolution in MECs. Electrochemical analysis (linear scan voltammetry and electrochemical impedance spectroscopy) revealed the improved electrochemical activity and effective mass diffusion after coating with graphene. NF-G as cathode in MEC showed a significant enhancement in hydrogen production rate compared with nickel foam at a variety of biases. Noticeably, NF-G showed a comparable averaged hydrogen production rate (1.31 +/- 0.07 mL H2 mL(-1) reactor d(-1)) to Platinum/carbon (Pt/C) (1.32 +/- 0.07 mL H2 mL(-1) reactor d(-1)) at 0.8 V. Profitable energy recovery could be achieved by NF-G cathode at higher applied voltage, which performed the best hydrogen yield of 3.27 +/- 0.16 mol H2 mol(-1) acetate at 0.8 V and highest energy efficiency of 185.92 +/- 6.48% at 0.6 V. PMID- 26807529 TI - Towards better understanding of patient centric drug product development in an increasingly older patient population. AB - The substantial reduction in premature death and longevity is an achievement of modern societies and advances in technology, medical and pharmaceutical sciences. Derived from the effective management of acute and chronic diseases throughout the lifetime the typical age related, later life stage diseases will become more dominant characteristics in future patients as well as other age related impairments or life conditions. Naturally, this leads to patients with complex clinical and functional patterns that are accompanied by the necessity of therapeutic interventions and polypharmacy. With the increasing number of older people and especially those with very high age in the society, new distinct older patient populations are evolving that require patient centered therapies and drug products to maintain safety and efficacy as well as effectiveness. Understanding how the patient populations and their characteristics change from a clinical, daily functioning and a patient perspective is crucial to move towards patient centric drug products. PMID- 26807528 TI - High-throughput mapping of regulatory DNA. AB - Quantifying the effects of cis-regulatory DNA on gene expression is a major challenge. Here, we present the multiplexed editing regulatory assay (MERA), a high-throughput CRISPR-Cas9-based approach that analyzes the functional impact of the regulatory genome in its native context. MERA tiles thousands of mutations across ~40 kb of cis-regulatory genomic space and uses knock-in green fluorescent protein (GFP) reporters to read out gene activity. Using this approach, we obtain quantitative information on the contribution of cis-regulatory regions to gene expression. We identify proximal and distal regulatory elements necessary for expression of four embryonic stem cell-specific genes. We show a consistent contribution of neighboring gene promoters to gene expression and identify unmarked regulatory elements (UREs) that control gene expression but do not have typical enhancer epigenetic or chromatin features. We compare thousands of functional and nonfunctional genotypes at a genomic location and identify the base pair-resolution functional motifs of regulatory elements. PMID- 26807527 TI - Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. AB - The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response. PMID- 26807530 TI - Novel methods of drug administration for the treatment and care of older patients. AB - The number of older people globally is increasing, contributing to a growing burden of morbidity and mortality. With this shift in population demographic, comes a new challenge in terms of appropriate healthcare for the over 65 years age group. As medication is the principal therapeutic intervention, it is essential that it be fully optimised, to meet the needs of this heterogeneous population. The most common routes of drug administration are oral and injectable, which may display some limitations for older people, in cases of dysphagia or frailty for example. This review considers alternative methods of drug delivery to the norm, specifically discussing the nasal, pulmonary and transdermal routes, as well as novel orally disintegrating tablets. The changing physiology as ageing occurs must be considered in the development of novel drug delivery devices. This review considers the various aspects of ageing that will influence future drug formulation design and development. PMID- 26807531 TI - Solution Observation of Dimerization and Helix Handedness Induction in a Human Carbonic Anhydrase-Helical Aromatic Amide Foldamer Complex. AB - The design of synthetic foldamers to selectively bind proteins is currently hindered by the limited availability of molecular data to establish key features of recognition. Previous work has described dimerization of human carbonic anhydrase II (HCA) through self-association of a quinoline oligoamide helical foldamer attached to a tightly binding HCA ligand. A crystal structure of the complex provided atomic details to explain the observed induction of single foldamer helix handedness and revealed an unexpected foldamer-mediated dimerization. Here, we investigated the detailed behavior of the HCA-foldamer complex in solution by using NMR spectroscopy. We found that the ability to dimerize is buffer-dependent and uses partially distinct intermolecular contacts. The use of a foldamer variant incapable of self-association confirmed the ability to induce helix handedness separately from dimer formation and provided insight into the dynamics of enantiomeric selection. PMID- 26807532 TI - Pulmonary Embolism As a Consequence of Ultrasonographic Examination of Extremities for Suspected Venous Thrombosis: A Systematic Review. AB - Ultrasonographic examination for deep vein thrombosis (DVT) appears to be a safe diagnostic method, but a theoretical concern has been raised for dislodgment of thrombi during examination. We conducted a systematic review of the literature to identify reports of possible or confirmed pulmonary embolism (PE) as a consequence of ultrasonographic assessment of extremities in patients with suspected DVT. We searched PubMed for studies published in English from January 1, 1960, to April 10, 2015. We included all cohort studies, case series, and case reports that described PE as a consequence of ultrasonographic assessment of extremities. We excluded studies that reported assessment of areas other than extremities. We screened 3,626 articles, 15 of which reported the issue of clot dislodgement and embolization following ultrasonographic examination of the extremities, including 8 original case reports (7 men and 1 woman). DVTs were in the lower extremities in all eight cases: five in right and three in left lower extremity. In six cases, the femoral veins were involved, and a free-floating thrombus was reported in two cases. Compression ultrasonography was used in all cases, with or without adjunct techniques. Overall, there were seven confirmed and one probable PE cases, two of which had fatal outcomes. Clot embolization is a rare but potential complication of ultrasonic examination for DVT that can lead into PE. Radiologists and clinicians should be aware of this potentially serious phenomenon and avoid excessive pressure when performing ultrasonographic studies of the extremities. PMID- 26807533 TI - Spin phonon interactions and magnetodielectric effects in multiferroic BiFeO3 PbTiO3. AB - Here, we report the observation of magneto-dielectric and magneto-structural coupling in (1 - x)BiFeO3-xPbTiO3 i.e.(1 - x)BF-xPT) solid solutions with compositions in the vicinity of morphotropic phase boundary, as manifested by a combination of temperature dependent magnetic, Raman and dielectric measurements. Whilst x-ray diffraction and Raman spectroscopy suggest absence of any structural phase transition between 90-300 K, temperature dependent magnetic studies reveal magnetic anomalies in the solid solutions. These results are complemented by identical observations in the dielectric measurements at similar temperatures indicating a coupling between magnetic and electric order parameters. Further, Raman studies on rhombohedral i.e. x = 0.20 samples reveal a coupling between the magnetic structure and the lattice, causing spin-phonon interactions that are possibly responsible for observed magneto-dielectric effects. Our results illustrate that the phase transitions in BiFeO3-PbTiO3 system are fewer than expected and are attributed to a spatial averaging in an inhomogeneous albeit single-phase material due to clustering of Fe- or Ti-ions on different length scales. PMID- 26807535 TI - Prevalence and Characteristics of Enterotoxin B-Producing Staphylococcus aureus Isolated from Food Sources: A Particular Cluster of ST188 Strains was Identified. AB - The aim of this study was to investigate the prevalence and characteristics of staphylococcal enterotoxin B (SEB) producing Staphylococcus aureus (S. aureus) isolated from food sources. A total of 412 S. aureus isolates were recovered from 1970 milk and dairy samples (n = 236) and 2450 meat samples (n = 176) in China from 2009 to 2014. Of the 412 isolates, 124 isolates were tested positive for 1 or more classical staphylococcal enterotoxin (SE) genes using PCR, and 31 isolates were positive for seb gene and further proved to be SEB-producing. Four SE profiles were observed among 31 SEB-producing isolates when investigated using ELISA kit, that is, SEB (16 isolates), SEA+SEB (6 isolates), SEB+SEC (6 isolates), and SEB+SED (3 isolates). Thirteen sequence types (STs) were identified in the 31 SEB-producing S. aureus isolates using multilocus sequence typing (MLST). The 3 most detected STs were ST1 (7 isolates), ST188 (6 isolates), ST59 (3 isolates). Two distinct clusters were identified by pulsed-field gel electrophoresis (PFGE), each of which showed excellent consistency with ST188 and ST1 achieved by MLST, respectively. In summary, this study reveals that various SE profiles are observed in SEB-producing S. aureus isolates and the great part of SEB-producing S. aureus isolates are showed as clusters. Especially, a particular cluster of ST188 strains was observed in SEB-producing S. aureus isolates which was associated with outbreaks of SFP and needs further attention. PMID- 26807534 TI - Effect of Remote Ischaemic Conditioning in Oncology Patients Undergoing Chemotherapy: Rationale and Design of the ERIC-ONC Study--A Single-Center, Blinded, Randomized Controlled Trial. AB - Cancer survival continues to improve, and thus cardiovascular consequences of chemotherapy are increasingly important determinants of long-term morbidity and mortality. Conventional strategies to protect the heart from chemotherapy have important hemodynamic or myelosuppressive side effects. Remote ischemic conditioning (RIC) using intermittent limb ischemia-reperfusion reduces myocardial injury in the setting of percutaneous coronary intervention. Anthracycline cardiotoxicity and ischemia-reperfusion injury share common biochemical pathways in cardiomyocytes. The potential for RIC as a novel treatment to reduce subclinical myocyte injury in chemotherapy has never been explored and will be investigated in the Effect of Remote Ischaemic Conditioning in Oncology (ERIC-ONC) trial (clinicaltrials.gov NCT 02471885). The ERIC-ONC trial is a single-center, blinded, randomized, sham-controlled study. We aim to recruit 128 adult oncology patients undergoing anthracycline-based chemotherapy treatment, randomized in a 1:1 ratio into 2 groups: (1) sham procedure or (2) RIC, comprising 4, 5-minute cycles of upper arm blood pressure cuff inflations and deflations, immediately before each cycle of chemotherapy. The primary outcome measure, defining cardiac injury, will be high-sensitivity troponin-T over 6 cycles of chemotherapy and 12 months follow-up. Secondary outcome measures will include clinical, electrical, structural, and biochemical endpoints comprising major adverse cardiovascular clinical events, incidence of cardiac arrhythmia over 14 days at cycle 5/6, echocardiographic ventricular function, N terminal pro-brain natriuretic peptide levels at 3 months follow-up, and changes in mitochondrial DNA, micro-RNA, and proteomics after chemotherapy. The ERIC-ONC trial will determine the efficacy of RIC as a novel, noninvasive, nonpharmacological, low-cost cardioprotectant in cancer patients undergoing anthracycline-based chemotherapy. PMID- 26807536 TI - Comparative Responsiveness of the PROMIS Pain Interference Short Forms, Brief Pain Inventory, PEG, and SF-36 Bodily Pain Subscale. AB - PURPOSE: To compare the sensitivity to change and the responsiveness to intervention of the PROMIS Pain Interference short forms, Brief Pain Inventory (BPI), 3-item PEG scale, and SF-36 Bodily Pain subscale in a sample of patients with persistent musculoskeletal pain of moderate severity. METHODS: Standardized response means, standardized effect sizes, and receiver operating curve analyses were used to assess change between baseline and 3-month assessments in 250 participants who participated in a randomized clinical effectiveness trial of collaborative telecare management for moderate to severe and persistent musculoskeletal pain. RESULTS: The BPI, PEG, and SF-36 Bodily Pain measures were more sensitive to patient-reported global change than the PROMIS Pain Interference short forms, especially for the clinically improved group, for which the change detected by the PROMIS short forms was not statistically significant. The BPI was more responsive to the clinical intervention than the SF-36 Bodily Pain and PROMIS Pain Interference measures. Post hoc analyses exploring these findings did not suggest that differences in content or rating scale structure (number of response options or anchoring language) adequately explained the observed differences in the detection of change. CONCLUSIONS: In this clinical trial, the BPI and PEG measures were better able to detect change than the SF-36 Bodily Pain and PROMIS Pain Interference measures. PMID- 26807537 TI - Poststroke Rehabilitation and Restorative Care Utilization: A Comparison Between VA Community Living Centers and VA-contracted Community Nursing Homes. AB - BACKGROUND: Effective poststroke rehabilitation care can speed patient recovery and minimize patient functional disabilities. Veterans affairs (VA) community living centers (CLCs) and VA-contracted community nursing homes (CNHs) are the 2 major sources of institutional long-term care for Veterans with stroke receiving care under VA auspices. OBJECTIVES: This study compares rehabilitation therapy and restorative nursing care among Veterans residing in VA CLCs versus those Veterans in VA-contracted CNHs. RESEARCH DESIGN: Retrospective observational. SUBJECTS: All Veterans diagnosed with stroke, newly admitted to the CLCs or CNHs during the study period who completed at least 2 Minimum Data Set assessments postadmission. MEASURES: The outcomes were numbers of days for rehabilitation therapy and restorative nursing care received by the Veterans during their stays in CLCs or CNHs as documented in the Minimum Data Set databases. RESULTS: For rehabilitation therapy, the CLC Veterans had lower user rates (75.2% vs. 76.4%, P=0.078) and fewer observed therapy days (4.9 vs. 6.4, P<0.001) than CNH Veterans. However, the CLC Veterans had higher adjusted odds for therapy (odds ratio=1.16, P=0.033), although they had fewer average therapy days (coefficient= 1.53+/-0.11, P<0.001). For restorative nursing care, CLC Veterans had higher user rates (33.5% vs. 30.6%, P<0.001), more observed average care days (9.4 vs. 5.9, P<0.001), higher adjusted odds (odds ratio=2.28, P<0.001), and more adjusted days for restorative nursing care (coefficient=5.48+/-0.37, P<0.001). CONCLUSION: Compared with their counterparts at VA-contracted CNHs, Veterans at VA CLCs had fewer average rehabilitation therapy days (both unadjusted and adjusted), but they were significantly more likely to receive restorative nursing care both before and after risk adjustment. PMID- 26807539 TI - The Interplay Between Continuity of Care, Multimorbidity, and Adverse Events in Patients With Diabetes. AB - OBJECTIVES: To evaluate the impact of continuity of care and multimorbidity on health outcomes in patients with diabetes. RESEARCH DESIGN: Using a US claims database of insured patients, we identified those with incident diabetes between 2004 and 2008 and followed them until death, disenrollment, or December 31, 2010. Continuity of care was defined using Breslau's Usual Provider of Continuity (UPC; proportion of visits to the usual or predominant provider within 2 y of diabetes diagnosis). Multivariable logistic regression was used to determine the association between UPC in the first 2 years after diabetes diagnosis and subsequent 1-year composite primary outcome of all-cause hospitalization or death in year 3 in patients with/without multimorbidity. RESULTS: Of the 285,231 patients with incident diabetes, 74% had multimorbidity; their average age was 53 years (SD=10.5) and 49% were female. A total of 77,270 (27%) individuals had a mean UPC>=75% in the first 2 years. During year 3 of follow-up, 33,632 (12%) patients died or were hospitalized for any cause. Greater continuity of care (UPC>=75%) was associated with reduced risk of subsequent death or hospitalization [7.2% vs. 13.5%; adjusted odds ratio (aOR)=0.72; 95% CI, 0.70 0.75]. Although multimorbidity was independently associated with an increased risk of our primary composite endpoint (13.4% vs. 7.2%; aOR=1.26; 95% CI, 1.21 1.30), the association between greater continuity and better outcomes was similar in those with multimorbidity (aOR=0.71; 95% CI, 0.69-0.71) as in those without (aOR=0.75; 95% CI, 0.71-0.80). CONCLUSIONS: In patients with incident diabetes, greater continuity of care is associated with improved outcomes, irrespective of whether or not they have multimorbidity. PMID- 26807540 TI - A Detailed Exploration Into the Association of Prescribed Opioid Dosage and Overdose Deaths Among Patients With Chronic Pain. AB - BACKGROUND: High opioid dosage has been associated with overdose, and clinical guidelines have cautioned against escalating dosages above 100 morphine equivalent mg (MEM) based on the potential harm and the absence of evidence of benefit from high dosages. However, this 100 MEM threshold was chosen somewhat arbitrarily. OBJECTIVE: To examine the association of prescribed opioid dosage as a continuous measure in relation to risk of unintentional opioid overdose to identify the range of dosages associated with risk of overdose at a detailed level. METHODS: In this nested case-control study with risk-set sampling of controls, cases (opioid overdose decedents) and controls were identified from a population of patients of the Veterans Health Administration who were prescribed opioids and who have a chronic pain diagnosis. Unintentional fatal opioid analgesic overdose was measured from National Death Index records and prescribed opioid dosage from pharmacy records. RESULTS: The average prescribed opioid dosage was higher (P<0.001) for cases (mean=98.1 MEM, SD=112.7; median=60, interquartile range, 30-120), than controls (mean=47.7 MEM, SD=65.2; median=25, interquartile range, 15-45). In a ROC analysis, dosage was a moderately good "predictor" of opioid overdose death, indicating that, on average, overdose cases had a prescribed opioid dosage higher than 71% of controls. CONCLUSIONS: A clear cut-point in opioid dosage to distinguish between overdose cases and controls was not found. However, lowering the recommended dosage threshold below the 100 MEM used in many recent guidelines would affect proportionately few patients not at risk for overdose while potentially benefitting many of those at risk for overdose. PMID- 26807541 TI - Pyrrole: An emerging scaffold for construction of valuable therapeutic agents. AB - Pyrrole derivatives comprise a class of biologically active heterocyclic compounds which can serve as promising scaffolds for antimicrobial, antiviral, antimalarial, antitubercular, anti-inflammatory and enzyme inhibiting drugs. Due to their inimitable anticancer and anti-tubercular properties, researchers were inspired to develop novel pyrrole derivatives for the treatment of MDR pathogens. In the present review the main target is to focus on the development of pyrrole mimics, with emphasis based on their structure activity relationship (SAR). The present review is being obliging for the future development of pyrrole therapeutics. PMID- 26807542 TI - Synthesis and evaluation of dual antiplatelet activity of bispidine derivatives of N-substituted pyroglutamic acids. AB - N-aralkylpyroglutamides of substituted bispidine were prepared and evaluated for their ability to inhibit collagen induced platelet aggregation, both in vivo and in vitro. Some compounds showed high anti-platelet efficacy (in vitro) of which six inhibited both collagen as well as U46619 induced platelet aggregation with concentration dependent anti-platelet efficacy through dual mechanism. In particular, the compound 4j offered significant protection against collagen epinephrine induced pulmonary thromboembolism as well as ferric chloride induced arterial thrombosis, without affecting bleeding tendency in mice. Therefore, the present study suggests that the compound 4j displays a remarkable antithrombotic efficacy much better than aspirin and clopidogrel. PMID- 26807543 TI - Galactose conjugated platinum(II) complex targeting the Warburg effect for treatment of non-small cell lung cancer and colon cancer. AB - Malignant neoplasms exhibit a higher rate of glycolysis than normal cells; this is known as the Warburg effect. To target it, a galactose-conjugated (trans-R,R cyclohexane-1,2-diamine)-2-chloromalonato-platinum(II) complex (Gal-Pt) was designed, synthesized, and evaluated in five human cancer cell lines and against two different xenograft tumour models. Gal-Pt exhibits much higher aqueous solubility (over 25 times) and improved cytotoxicity than oxaliplatin, especially in human colon (HT29) and lung (H460) cancer cell lines. The safety profile of Gal-Pt was investigated in vivo by exploring the maximum tolerated dose (MTD) and animal mortality rate. The ratios of the animal lethal dosage values to the cytotoxicity in HT29 (LD50/IC50) showed that Gal-Pt was associated with an increased therapeutic index by over 30-fold compared to cisplatin and oxaliplatin. We evaluated in vivo antitumor activity by single agent intravenous treatment comparison studies of Gal-Pt (50 mg/kg as 65% MTD) and cisplatin (3 mg/kg, as 80% MTD) in a H460 lung cancer xenograft model, and with oxaliplatin (7 mg/kg, as 90% MTD) in a HT29 colon cancer xenograft model. The results show that Gal-Pt was more efficacious against H460 than cisplatin, and had superior potency in HT29 cells compared to oxaliplatin under nontoxic dosage conditions. The dependency between cytotoxicity of Gal-Pt and glucose transporters (GLUTs) was investigated by using quercetin as an inhibitor of GLUTs in HT29 cells. The cytotoxic potency of Gal-Pt was highly reduced by the inhibitor, suggesting that the uptake of Gal-Pt was regulated by glucose transporters. The GLUT mediated transportability and cellular uptake of Gal-Pt was also demonstrated using a fluorescent glucose bioprobe in HT29 competition assay. PMID- 26807544 TI - Potent dual inhibitors of Plasmodium falciparum M1 and M17 aminopeptidases through optimization of S1 pocket interactions. AB - Malaria remains a global health problem, and though international efforts for treatment and eradication have made some headway, the emergence of drug-resistant parasites threatens this progress. Antimalarial therapeutics acting via novel mechanisms are urgently required. Plasmodium falciparum M1 and M17 are neutral aminopeptidases which are essential for parasite growth and development. Previous work in our group has identified inhibitors capable of dual inhibition of PfA-M1 and PfA-M17, and revealed further regions within the protease S1 pockets that could be exploited in the development of ligands with improved inhibitory activity. Herein, we report the structure-based design and synthesis of novel hydroxamic acid analogues that are capable of potent inhibition of both PfA-M1 and PfA-M17. Furthermore, the developed compounds potently inhibit Pf growth in culture, including the multi-drug resistant strain Dd2. The ongoing development of dual PfA-M1/PfA-M17 inhibitors continues to be an attractive strategy for the design of novel antimalarial therapeutics. PMID- 26807545 TI - Novel dihydropyrazole-chromen: Design and modulates hTERT inhibition proliferation of MGC-803. AB - Dominant-negative mutant of telomerase hTERT was demonstrated to show selective anticancer effects in tumor cells. But, an effective hTERT inhibitor with high selectivity has not been developed so far. Focused on hTERT, a novel dihydropyrazole-chromen (13k) controlling hTERT was designed. Title compound 13k occupied high antiproliferative activity against MGC-803 cells with IC50 value 1.41 MUM, but it manifested obvious un-toxic effect on human normal gastric mucosa cells with the IC50 2.3 mM. Treated with compound 13k, the further inhibition mechanisms by modulating hTERT was explored, the results showed that expression of hTERT was clearly modulated, and then beta-catenin activation was decreased, thereby the expression of downstream signaling molecules including c myc and cyclin D1 was modulated, leading to inhibition MGC-803 cells proliferation. PMID- 26807546 TI - Design, synthesis and biological evaluation of novel asperphenamate derivatives. AB - A series of novel asperphenamate derivatives were designed and synthesized, including series I (the A-phenyl group replaced with various aromatic heterocycles) and series II (the acyl group substituted by sulfonyl group). All compounds have been screened for their antiproliferative activity in vitro against MCF-7, HeLa, and BEL-7402 cell lines by the standard MTT method. Structure-activity relationship studies displayed the heterocycle type played an important role in activity. Six-membered ring derivatives displayed more potency than five-membered ring and the sulfonyl group in A-ring region made an important contribution to activity. Among all derivatives, tosyl derivative 8c exhibited the greatest potency in three human cancer cell lines. Especially in MCF-7 cells, the cellular potency of 8c was approximately 3.0-fold more potent than that of cisplatin. Firstly, the mechanism of cell death induced by 8c in MCF-7 cells was investigated. The results showed that the cell death was induced by autophagy instead of apoptosis or cell cycle arrest. Further studies indicated that 8c might induce autophagic cell death in HeLa and BEL-7402 cell lines. PMID- 26807547 TI - Discovery of antiviral molecules for dengue: In silico search and biological evaluation. AB - BACKGROUND: Dengue disease is a global disease that has no effective treatment. The dengue virus (DENV) NS2B/NS3 protease complex is a target for designing specific antivirals due to its importance in viral replication and its high degree of conservation. METHODS: NS2B/NS3 protease complex structural information was employed to find small molecules that are capable of inhibiting the activity of the enzyme complex. This inhibitory activity was probed with in vitro assays using a fluorescent substrate and the complex NS2B/NS3 obtained by recombinant DNA techniques. HepG2 cells infected with dengue virus serotype 2 were used to test the activity against dengue virus replication. RESULTS: A total of 210,903 small molecules from PubChem were docked in silico to the NS2B/NS3 structure (PDB: 2FOM) to find molecules that were capable of inhibiting this protein complex. Five of the best 500 leading compounds, according to their affinity values (-11.6 and -13.5 kcal/mol), were purchased. The inhibitory protease activity on the recombinant protein and antiviral assays was tested. CONCLUSIONS: Chemicals CID 54681617, CID 54692801 and CID 54715399 were strong inhibitors of NS2B/NS3, with IC50 values (MUM) and percentages of viral titer reductions of 19.9, 79.9%; 17.5, 69.8%; and 9.1, 73.9%, respectively. Multivariate methods applied to the molecular descriptors showed two compounds that were structurally different from other DENV inhibitors. GENERAL SIGNIFICANCE: This discovery opens new possibilities for obtaining drug candidates against Dengue virus. PMID- 26807548 TI - Unique Use of Alkylation for Chemo-Redox Activity by a Pt(IV) Prodrug. AB - Resistance towards chemotherapeutics displayed by cancer cells is a significant stumbling block against fruitful cisplatin-based therapy. A unique dual-acting chemotherapeutic modality, Platin-B, a prodrug of cisplatin and pipobroman mimicking alkylating agent, was constructed to circumvent tumor resistance. Platin-B exhibited a superior cytotoxicity profile in cisplatin-resistant cancer cells. Enhanced activity and the ability to overcome cancer-induced resistance of Platin-B was related to adduct formation with intracellular glutathione, followed by the activity of Platin-B on the mitochondria of cells, along with its conventional nuclear activity. Alkylating moieties present on Platin-B enhanced its cellular and subcellular concentration and protected it from early drug sequestration by biological thiols. PMID- 26807549 TI - The Subcutaneous Implantable Cardioverter Defibrillator. AB - The subcutaneous implantable cardioverter defibrillator (S-ICD) is a subcutaneous alternative to conventional transvenous ICD (TV-ICD) systems, which have previously been shown to treat life-threatening ventricular tachyarrhythmias in cardiac disease patients. A review of the literature reveals that S-ICDs have similar shock efficacy rates for both induced and spontaneous ventricular tachyarrhythmias when compared with TV-ICDs. Furthermore, S-ICDs seem to have a higher specificity for withholding therapy when supraventricular tachycardia is present compared with TV-ICDs. The advantages of the S-ICD system are numerous: fewer vascular complications including thrombosis and hemothorax, avoidance of fluoroscopy, and an easier means of lead replacement. These advantages make the S ICD system most suitable for younger patients who may require replacements in later life, those with abnormal venous anatomy, and individuals prone to infection and/or central vein thrombosis. However, S-ICDs are not without their complications and are associated with a higher incidence of inappropriate shocks secondary to T wave oversensing. S-ICDs also lack antitachycardia pacing, making them a suboptimal device in patients with recurrent monomorphic ventricular tachycardia who would otherwise benefit from the antitachycardia pacing offered in TV-ICDs. Lastly, the limited number of long-term randomized, head-to-head studies involving direct comparison with TV-ICDs poses a challenge in the implementation of the S-ICD. PMID- 26807550 TI - Sabril(r) registry 5-year results: Characteristics of adult patients treated with vigabatrin. AB - Vigabatrin (Sabril(r)), approved in the US in 2009, is currently indicated as adjunctive therapy for refractory complex partial seizures (rCPS) in patients >= 10 years old who have responded inadequately to several alternative treatments and as monotherapy for infantile spasms (IS) in patients 1 month to 2 years of age. Because of reports of vision loss following vigabatrin exposure, FDA approval required a risk evaluation mitigation strategy (REMS) program. Vigabatrin is only available in the US through Support, Help, And Resources for Epilepsy (SHARE), which includes a mandated registry. This article describes 5 years of demographic and treatment exposure data from adult patients (>= 17 years old) in the US treated with vigabatrin and monitored in the ongoing Sabril(r) registry. Registry participation is mandatory for all US Sabril(r) prescribers and patients. A benefit-risk assessment must be documented by the physician for a patient to progress to maintenance therapy, defined as 1 month of vigabatrin treatment for patients with IS and 3 months for patients with rCPS. Ophthalmologic assessments must be documented during and after completion of therapy. As of August 26, 2014, a total of 6823 patients were enrolled in the registry, of which 1200 were adults at enrollment. Of these patients, 1031 (86%) were naive to vigabatrin. The majority of adult patients (n=783, 65%) had previously been prescribed >= 4 AEDs, and 719 (60%) were receiving >= 3 concomitant AEDs at vigabatrin initiation. Prescribers submitted an initial ophthalmological assessment form for 863 patients; an ophthalmologic exam was not completed for 300 (35%) patients and thus, were considered exempted from vision testing. Of these patients, 128 (43%) were exempted for neurologic disabilities. Clinicians discontinued treatment in 8 patients because of visual field deficits (VFD) (5 patients naive to vigabatrin and 3 patients previously exposed). Based on Kaplan-Meier survival estimates, it is estimated that approximately 71%, 55%, and 40% of adult patients naive to vigabatrin would remain in the registry at 3, 6, and 12 months, respectively. These demographic data suggest that a proportion of adult patients remain on vigabatrin long-term despite the risks of adverse events and significant underlying AED resistance and neurologic disease. PMID- 26807551 TI - Prolonged Dye Release from Mesoporous Silica-Based Imaging Probes Facilitates Long-Term Optical Tracking of Cell Populations In Vivo. AB - Nanomedicine is gaining ground worldwide in therapy and diagnostics. Novel nanoscopic imaging probes serve as imaging tools for studying dynamic biological processes in vitro and in vivo. To allow detectability in the physiological environment, the nanostructure-based probes need to be either inherently detectable by biomedical imaging techniques, or serve as carriers for existing imaging agents. In this study, the potential of mesoporous silica nanoparticles carrying commercially available fluorochromes as self-regenerating cell labels for long-term cellular tracking is investigated. The particle surface is organically modified for enhanced cellular uptake, the fluorescence intensity of labeled cells is followed over time both in vitro and in vivo. The particles are not exocytosed and particles which escaped cells due to cell injury or death are degraded and no labeling of nontargeted cell populations are observed. The labeling efficiency is significantly improved as compared to that of quantum dots of similar emission wavelength. Labeled human breast cancer cells are xenotransplanted in nude mice, and the fluorescent cells can be detected in vivo for a period of 1 month. Moreover, ex vivo analysis reveals fluorescently labeled metastatic colonies in lymph node and rib, highlighting the capability of the developed probes for tracking of metastasis. PMID- 26807552 TI - Latent class analysis of the Apathy Scale does not identify subtypes of apathy in general population-based older persons. AB - OBJECTIVES: To identify clinically relevant subtypes of apathy in older persons using latent class analysis (LCA) and investigate the distribution of different characteristics across these subtypes. MEASUREMENTS: Cross-sectional data of 122 older persons (mean age 84 years, 60% female) participating in the general population-based PROactive Management Of Depression in the Elderly study, with apathy according to a score of 14 or higher on the Apathy Scale, were included for LCA. All 14 items of the Apathy Scale were used as indicator variables. Several characteristics were examined including sociodemographics, depressive, and anxiety symptoms; global cognitive function; quality of life indicators; hazardous alcohol intake (drinking >= 14 consumptions per week); and perceived chronic pain. RESULTS: Three distinct LCA classes were found classifying 17%, 7%, and 76% of the participants respectively. Individuals in the first class had a higher level of education and were less likely to live alone. Those in the second class had higher apathy and depression scores, lived more frequently alone and used more alcohol. Individuals in the third class showed a lower level of education and worse cognitive function. In multivariable multinomial analyses, only a lower educational level and higher scores on the Apathy Scale were significant predictors for class membership. CONCLUSION: Differences between LCA derived classes were minimal, suggesting that in a general population-based cohort the Apathy Scale measures a homogeneous construct. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26807553 TI - General Assembly of Twisted Trigonal-Prismatic Nonanuclear Silver(I) Clusters. AB - A general class of C3 -symmetric Ag9 clusters, [Ag9 S(tBuC6 H4 S)6 (dpph)3 (CF3 SO3 )] (1), [Ag9 (tBuC6 H4 S)6 (dpph)3 (CF3 SO3 )2 ]?CF3 SO3 (2), [Ag9 (tBuC6 H4 S)6 (dpph)3 (NO3 )2 ] ?NO3 (3), and [Ag9 (tBuC6 H4 S)7 (dpph)3 (Mo2 O7 )0.5 ]2 ?2 CF3 COO (4) (dpph=1,6-bis(diphenylphosphino)hexane), with a twisted trigonal prism geometry was isolated by the reaction of polymeric {(HNEt3 )2 [Ag10 (tBuC6 H4 S)12 ]}n , 1,6-bis(diphenylphosphino)hexane, and various silver salts under solvothermal conditions. The structures consist of discrete clusters constructed from a girdling Ag9 twisted trigonal prism with the top and bottom trigonal faces capped by diverse anions (i.e., S(2-) and CF3 SO3 (-) for compound 1, 2*CF3 SO3 ( ) for compound 2, 2*NO3 (-) for compound 3, and tBuC6 H4 S(-) and Mo2 O7 (2-) for compound 4). This trigonal prism is bisected by another shrunken Ag3 trigon at its waist position. Interestingly, two inversion-related Ag9 trigonal-prismatic clusters are dimerized by the Mo2 O7 (2-) ion in compound 4. The twist is amplified by the bulkier thiolate, which also introduces high steric-hindrance for the capping ligand, that is, the longer dpph ligand. Four more silver-sulfur clusters (namely, compounds 5-8) with their nuclearity ranging from 6-10 were solely characterized by single-crystal X-ray diffraction to verify the above described synergetic effect of mixed ligands in the construction of Ag9 twisted trigonal prisms. Surprisingly, only cluster 1 emits yellow luminescence at lambda=584 nm at room temperature, which may be attributed to a charge transfer from the S 3p orbital to the Ag 5s orbital, or mixed with metal-centered (MC) d(10) ->d(9) s(1) transitions. Upon cooling from 300 to 80 K, the emission intensity was enhanced along with a hypsochromic shift. The good linear relationship between the maximum emission intensity and the temperature for compound 1 in the range of 180-300 K indicates that this is a promising molecular luminescent thermometer. Furthermore, cyclic voltammetric studies indicated that the diffusion- and surface-controlled redox processes were determined for compounds 1 and 3 as well as compound 4, respectively. PMID- 26807554 TI - Teens' Self-Efficacy to Deal with Dating Violence as Victim, Perpetrator or Bystander. AB - Multiple studies have demonstrated that adolescent dating violence is highly prevalent and associated with internalizing and externalizing problems. A number of prevention initiatives are being implemented in North-American high schools. Such initiatives do not only aim to raise awareness among potential victims and offenders but also among peer bystanders. Since teenagers mainly reach out to their peers when experiencing adversity, it is important to address adolescents' efficiency to deal with witnessing dating violence or with friends disclosing dating abuse, in addition to increasing ability to deal with experienced dating violence victimization or perpetration. The aim of this study is to explore adolescents' self-efficacy to deal with dating violence victimization and perpetration in their relationships and those of their peers. A paper-and-pencil questionnaire was completed by 259 14-18 years olds in Quebec, Canada. The data allows building insight into adolescents' confidence to reach out for help or to help others in a situation of dating violence victimization and perpetration. We also considered the impact of gender and dating victimization history. Results suggest that dating violence prevention can build on teens' self-efficacy to deal with dating violence and offer them tools to do so efficiently. PMID- 26807555 TI - Surface Antigen Profiling of Helicobacter pylori-Infected and -Uninfected Gastric Cancer Cells Using Antibody Microarray. AB - BACKGROUND: Comprehensive immunophenotyping cluster of differentiation (CD) antigens in gastric adenocarcinoma, specifically between Helicobacter pylori infected and -uninfected gastric cancer patients by using DotScan(TM) antibody microarray has not been conducted. Current immunophenotyping techniques include flow cytometry and immunohistochemistry are limited to the use of few antibodies for parallel examination. We used DotScan(TM) antibody microarray consisting 144 CD antibodies to determine the distribution of CD antigens in gastric adenocarcinoma cells and to elucidate the effect of H. pylori infection toward CD antigen expression in gastric cancer. METHODS: Mixed leukocytes population derived from gastric adenocarcinoma patients were immunophenotyped using DotScan(TM) antibody microarray. AGS cells were infected with H. pylori strains and cells were captured on DotScan(TM) slides. RESULTS: Cluster of differentiation antigens involved in perpetuating the tolerance of immune cells to tumor cells was upregulated in gastric adenocarcinoma cells compared to normal cells. CD279 which is essential in T cells apoptosis was found to be upregulated in normal cells. Remarkably, H. pylori-infected gastric cancer patients exhibited upregulated expression of CD27 that important in maintenance of T cells. Infection of cagA+ H. pylori with AGS cells increased CD antigens expression which involved in cancer stem cell while cagA- H. pylori polarized AGS cells to express immune-regulatory CD antigens. Increased CD antigens expression in AGS cells infected with cagA+ H. pylori were also detected in H. pylori-infected gastric cancer patients. CONCLUSION: This study suggests the tolerance of immune system toward tumor cells in gastric cancer and distinct mechanisms of immune responses exploited by different H. pylori strains. PMID- 26807556 TI - Hyperviscosity in primary Sjogren's syndrome: clinical implications. AB - AIM: Increased serum viscosity is recognized in primary Sjogren's syndrome (pSS); however, a classic hyperviscosity syndrome (HVS) is rare. We compared the clinical and serological profile among three groups of pSS patients: (i) with HVS; (ii) with high serum viscosity (>= 1.9 cP [centipoises]) but without HVS; and (iii) with normal viscosity (< 1.9 cP). METHODS: We identified four pSS patients with HVS and retrospectively assessed their clinical/serological features. We included as controls 62 pSS patients and registered their clinical features. We also measured the serum viscosity, C3, C4, immunoglobulins and evaluated the European League Against Rheumatism SS Disease Activity Index (ESSDAI) score at the last visit. We used chi2 , Mann-Whitney U-tests and logistic regression analysis. RESULTS: Patients were predominantly female (95%), mean age 54 +/- 14.2 years, median disease duration 9 years. All the HVS cases were diagnosed concomitantly with the onset of SS and had higher titers of immunoglobulin G (IgG), IgM, IgA and a higher prevalence of vasculitis, neutropenia, lymphopenia and splenomegaly. At the multivariate analysis, the variables vasculitis odds ratio (OR) 14.8 (95% CI 1.3-99, P = 0.02) and splenomegaly OR 25.3 (95% CI 1.68-380, P = 0.01) remained associated with HSV. Viscosity levels correlated with rheumatoid factor titers. Thirty (48.3%) patients had high viscosity but without HSV; this group had higher median ESSDAI scores and more vasculitis than patients with normal viscosity. CONCLUSION: High viscosity was present in almost half of the patients and was associated with vasculitis and higher activity scores. Conversely, HVS was infrequent and was associated with vasculitis and splenomegaly. It seems that both conditions have different physiopathological, clinical and treatment implications. PMID- 26807557 TI - Letter From the Editor. PMID- 26807558 TI - Regarding: Vulvar Reconstruction by Perforator Flaps. Algorithm for Flap Choice Based on the Topography of the Defect. PMID- 26807559 TI - Letter to the Editor on "Should All Cases of High-Grade Serous Ovarian, Tubal, and Primary Peritoneal Carcinomas Be Reclassified as Tubo-Ovarian Serous Carcinoma?" Int J Gynecol Cancer 2015;25: 1201-1207. PMID- 26807560 TI - Loss of Mismatch Repair Protein Expression in Unselected Endometrial Adenocarcinoma Precursor Lesions. AB - OBJECTIVE: The benefit of evaluating the precursor of endometrial carcinoma, endometrial hyperplasia (intraepithelial neoplasia [EIN]), for loss of mismatch repair (MMR) protein expression and Lynch syndrome has yet to be determined. The present study aims to establish the incidence and type of loss of MMR protein expression in unselected premalignant lesions of endometrial adenocarcinoma, as well as the agreement of immunohistochemical staining in pretreatment endometrial biopsy (EMB) specimens with subsequent uterine resections. METHODS: A retrospective review identified 112 endometrial biopsies meeting criteria for endometrial EIN. Slides made from tissue microarray blocks were evaluated using antibodies against MLH1, PMS2, MSH2, and MSH6. Cases with a deficit in MLH1 were evaluated for gene promoter hypermethylation by polymerase chain reaction analysis. Fifty-four subsequent hysterectomy specimens were retrieved and assessed for MMR protein expression. RESULTS: Of the 112 endometrial biopsies with EIN, 4.5% (5/112) exhibited loss of MMR protein expression. The majority (4/5) demonstrated a deficit of MLH1, of which all exhibited inactivation via promoter hypermethylation. A single case displayed an absence of MSH6. Age was not significantly associated with MMR deficiency. There was no significant association between MMR status in the EMB and a subsequent diagnosis of cancer. Immunohistochemical staining in all successive hysterectomy cases was concordant with the pattern observed in the EMB specimen. CONCLUSIONS: Sporadic hypermethylation of MLH1 seems to be the primary mechanism underlying defective MMR protein expression in EIN. Among our cohort, only 1 patient (<1%) had a mutation suggestive of a hereditary inheritance. Hence, the utility of evaluating EIN for MMR protein expression as a screen for Lynch syndrome is limited, regardless of age. PMID- 26807561 TI - Clinical and Pathological Characteristics of Incidental Diagnostic Early Occult Malignancy After Risk-Reducing Salpingo-Oophorectomy in BRCA Mutation Carriers. AB - OBJECTIVE: Carriers of familial BRCA mutations are at high risk of early development of ovarian tubal or peritoneal cancers. The definite preventative treatment for these cases is early, risk-reducing, bilateral salpingo oophorectomy (BSO). The aims of the study were to describe the incidence and source of early occult malignancy after risk-reducing salpingo-oophorectomy in carriers of Ashkenazi Jewish BRCA mutations and to characterize the clinical and pathological features of this unique population. METHODS: Data were collected retrospectively regarding women who underwent BSO in our gynecologic oncology unit from January 2002 through July 2012, after a positive test for a BRCA1 or BRCA2 mutation. RESULTS: The following 92 cases of BRCA mutations were included: 53 BRCA1, 37 BRCA2, and 2 with both mutations. After risk-reducing salpingo oophorectomy, 5 (5.4%) of the patients were found to have early occult adnexal malignancy upon pathology study. All 5 had the BRCA1 185 del-AG mutation. Three of the 5 malignancies originated from the ovaries and 2 in the fallopian tubes with no involvement of the ovaries. CONCLUSIONS: A 5.4% incidence of early occult malignancy in adnexal pathology of BSO was found in carriers of Ashkenazi Jewish BRCA mutations. Two cases with malignant origins within the fallopian tube, while sparing the ovaries in their entirety, support the fallopian tubes as the originating organ for some ovarian or peritoneal malignancies in BRCA mutation carriers. PMID- 26807562 TI - Impact of Chemotherapy Beyond the Third Line in Patients With Recurrent Epithelial Ovarian Cancer. AB - OBJECTIVES: The goal of this study was to determine the benefit in terms of time disease control (TDC) achieved by the succession of chemotherapy beyond the third line in patients treated for recurrent epithelial ovarian cancer. Secondary objectives were to identify patients who benefited from treatments beyond 3 lines and to estimate overall survival and disease-free progression lengths. MATERIALS AND METHODS: The cohort of 122 patients was identified from a pharmacy database of patients treated with chemotherapy between 1992 and 2010. The evaluation of benefit obtained by each line was based on TDC duration, defined as the interval between the beginning of the treatment and the date of progressive disease or death. RESULTS: Median TDC durations was 4.15 (0-54.7), 4 (0-21.7), 3.34 (0 29.6), 4.97 (0-29.2), and 3.13 months (0-15) for the fourth to eighth lines, respectively. Time to disease control was longer than 6 months in 34% to 40% of patients treated by lines 4 to 8. The most important factor influencing TDC length beyond the third line was the TDC duration observed in the 2 previous lines of therapy. Median overall survival after the third line was 15.3 months (95% confidence interval, 12-20 months). Factors associated with longer overall survival after 3 lines were performance status lower than 2 (P = 0.0058), no hepatic metastasis (P = 0.0098), no pulmonary metastasis (P = 0.0003), and platinum sensitivity (P = 0.04) CONCLUSIONS: These results may justify the administration of chemotherapy beyond the third line, in particular when the 2 previous lines are effective and resulted in disease control longer than 6 months. PMID- 26807563 TI - The Impact of Obesity on the 30-day Morbidity and Mortality After Surgery for Ovarian Cancer. AB - OBJECTIVES: To examine the effect of body mass index (BMI) on postoperative 30 day morbidity and mortality after surgery for ovarian cancer (OC). METHODS: Patients with OC were identified from the American College of Surgeons National Surgical Quality Improvement Program from 2005 to 2011. Women were divided into 3 groups: nonobese (BMI <30 kg/m), obese (30 to <40 kg/m), and morbidly obese (>=40 kg/m). Multivariable logistic regression models were performed. RESULTS: Of 2061 women included in this study, 1336 (65%) were nonobese, 560 (27%) were obese, and 165 (8%) were morbidly obese. The overall 30-day mortality and morbidity rates for the entire cohort were 2% and 31%, respectively. In multivariate analyses adjusting for confounders, both obese (odds ratio [OR], 0.9; 95% confidence interval [CI], 0.4-2.0; P = 0.87) and morbid obesity (OR, 0.8; 95% CI, 0.1-3.0; P = 0.73) were not significant predictors of increased 30-day postoperative mortality. Likewise, rates of any complication in 30 days were comparable between nonobese, obese, and morbidly obese patients (31% vs. 28% vs. 33%, respectively; P = 0.35) with no significant difference even after adjusting for other confounders (OR, 0.9; 95% CI, 0.7-1.1; P = 0.26 and OR, 1.1; 95% CI, 0.7-1.6; P = 0.70, respectively). Obese and morbidly obese patients were more likely to have diabetes, hypertension requiring medications, cardiac morbidities, higher American Society of Anesthesiologists class, and leukocytosis and less likely to have weight loss before surgery. CONCLUSIONS: With appropriate control for confounding comorbidities, the 30-day morbidity and mortality rates for the obese and morbidly obese patients undergoing surgery for OC do not seem to differ. Therefore, reported inferior long-term survival for these patients is likely related to a different phase of their disease and treatment process and is deserving of further investigation. PMID- 26807564 TI - Comparison of Serum Human Epididymis Protein 4 and Carbohydrate Antigen 125 as Markers in Endometrial Cancer: A Meta-Analysis. AB - OBJECTIVES: For patients with endometrial cancer (EC), the screening value of serum human epididymis protein 4 (HE4) remains controversial. We performed meta analyses to compare the screening accuracy of serum HE4 and carbohydrate antigen 125 (CA125) for EC. MATERIALS AND METHODS: A search of diagnostic test studies was performed in 5 English databases: Pubmed, Cochrane Library, Web of Science, Science Direct, and Elton Bryan Stephens Co or EBSCO; and 2 Chinese databases including China National Knowledge Infrastructure or CNKI and VIP (Weipu Database), from their inception dates to early July 2015. Two reviewers independently selected trials, conducted critical appraisal, and extracted data. Meta-analyses were performed to compare the screening accuracy between HE4 and CA125. Summary receiver operating characteristic curve and the area under the summary receiver operating characteristic curve were performed. Subgroup analysis, meta-regression, sensitivity analysis, and Egger plot and the Egger test were also conducted. RESULTS: Twenty-one studies were identified, and the methodological quality was generally fair. Meta-analyses revealed that the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratios for HE4 in screening EC were 0.56, 0.89, 6.41, 0.49, and 14.82, respectively, whereas the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for CA125 in screening EC were 0.32, 0.81, 2.15, 0.83, and 2.74, respectively. The areas under the summary receiver operating characteristic curves for HE4 and CA125 were 0.7778 and 0.5474, respectively. CONCLUSIONS: This study indicates that serum HE4 may be superior to CA125 in screening accuracy of EC. This conclusion has to be interpreted cautiously owing to high heterogeneity and some limitations. PMID- 26807565 TI - Evaluation of Preoperative Chest Imaging in Low-Risk Endometrial Cancer Patients. AB - OBJECTIVE: Current national guidelines recommend preoperative thoracic imaging for all patients undergoing surgery for endometrial cancer. The objective of this project was to report the incidence of pulmonary metastasis in endometrial cancer patients and describe tumor and patient characteristics to better identify a low risk population for thoracic involvement. We evaluated the ideal modality of preoperative imaging for both low-risk and high-risk populations based on the risk of pulmonary involvement. METHODS: A retrospective cross-sectional study of patients undergoing surgical evaluation for endometrial cancer at a single institution from 2010 to 2014 was performed. Low-risk patients were defined as having a preoperative pathology sample showing grade 1 or 2 endometrioid endometrial cancer and a physical examination not concerning for extrauterine disease spread. RESULTS: A total of 352 patients were evaluated, of which 327 (92.9%) had preoperative thoracic imaging. Twenty-six patients had benign pathology or no preoperative sampling, leaving 301 patients for analysis. There were 228 (75.7%) of 301 patients classified as low-risk by our criteria. There were 20 (8.8%) of 228 low-risk patients with initial imaging concerning for pulmonary metastasis, but follow-up showed no evidence of disease. No low-risk patients (0/228; 95% confidence interval [CI], 0%-0.02%) had pulmonary metastasis. There were 4 (1.3%) of 301 (95% CI, 0%-0.04%) patients diagnosed with pulmonary metastasis based on preoperative imaging, and 4 (1.3%) of 301 (95% CI, 0.01%-0.04%) patients with recurrent pulmonary disease. Median time to pulmonary recurrence was 20 months. CONCLUSIONS: The incidence of pulmonary metastasis found on preoperative imaging is exceptionally low in our defined low-risk population. All of the patients with pulmonary involvement either initially or upon recurrence had high-risk features. Given our findings, we would recommend that providers consider chest x-ray as the appropriate screening modality for the low-risk population and chest computed tomography for the high-risk population. PMID- 26807566 TI - Surgical Scar Site Recurrence in Patients With Cervical Cancer on 18F-FDG PET-CT: A Case-Control Study. AB - PURPOSE: The purpose of this study was to assess the role of fluorine 18 ((18)F) fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) in evaluating various parameters in patients with surgical scar site recurrence in cervical carcinoma. METHODS: Data of all patients with cervical cancer (n = 329) who underwent PET-CT at our institute between 2005 and 2013 was reviewed. Of these 329 patients, 132 patients who were surgically treated and underwent restaging/follow-up PET-CT were included in the present study for final analysis. Tumor recurrence at the abdominal surgical scar site was looked for. Abnormal uptakes suggestive of active disease at other sites were also noted. Maximum standardized uptake value was measured for all the lesions. Patients with scar site recurrence were taken as cases (n = 6), whereas the remaining patients served as controls (n = 126). Comparison with conventional imaging modalities was made wherever available. Histopathological examination was always sought for. RESULTS: The incidence of scar site recurrence after surgery was found to be 4.5% (6/117). A total of 56 of 132 patients had recurrent disease, including 6 patients with scar site recurrence. All of the patients with scar site recurrence also had recurrent disease at other sites (local, nodal, or distant). Conventional imaging modalities were available in 4 of these 6 patients and detected scar site recurrence in 3 of those 4 patients. In patients with scar site recurrence, the mean +/- SD time to scar site recurrence was 14.0 +/- 10.9 months (median, 10 months; range, 7-36 months). Significant difference was seen between cases and control for International Federation of Genecology and Oncology stage (P = 0.001) and nodal recurrence (P = 0.007). Additionally, age, nodal recurrence, distant recurrence, and scar site recurrence were significantly associated with death. CONCLUSIONS: Scar site recurrence carries a poor prognosis, and the incidence is much higher than previously known when PET-CT is used as a modality for its detection. PMID- 26807567 TI - The Value of Diffusion-Weighted Imaging in Predicting the Prognosis of Stage IB IIA Cervical Squamous Cell Carcinoma After Radical Hysterectomy. AB - OBJECTIVE: The aim of the study was to investigate the value of mean apparent diffusion coefficient (ADC(mean)) value in predicting the prognosis of stage IB IIA cervical squamous cell carcinoma (SCC) patients after radical hysterectomy. MATERIALS AND METHODS: A total of 126 patients who were with stage IB-IIA cervical SCC and underwent magnetic resonance imaging examination and radical hysterectomy were retrospectively investigated. Receiver operating characteristic curve was used to determine the cutoff values of ADC(mean) for predicting earlier recurrence (2 consecutive increases in the SCC antigen value of more than 1 ng/mL or elevation of greater than 1.5 ng/mL). Disease-free survival and overall survival were analyzed using the Kaplan-Meier method, and differences between the survival curves were examined using the log-rank test. RESULTS: Earlier recurrence was observed in 46 patients (36.2%) during a median follow-up of 22 months. The ADC(mean) value (P = 0.005), parametrial invasion (P = 0.049), and lymphovascular space invasion (P = 0.037) were significantly associated with earlier recurrence. Receiver operating characteristic curve identified that the cutoff value of ADC(mean) for predicting earlier recurrence was 0.785 * 10( 3)mm(2)/s. The ADC(mean) value, parametrial invasion, and lymphovascular space invasion were significantly associated with earlier recurrence. The hazard ratios were 7.33 (95% confidence interval [95% CI], 1.854-28.99), 4.88 (95% CI, 1.00 23.73), and 2.53 (95% CI, 1.058-6.052), respectively. Disease-free survival and overall survival rates of patients with the ADC(mean) less than 0.785 * 10( 3)mm(2)//s were significantly worse than those of patients with the ADC(mean) greater than or equal to 0.785 * 10(-3)mm(2)/s. CONCLUSIONS: Mean ADC was a good biomarker in predicting the prognosis of stage IB-IIA cervical SCC after radical hysterectomy. PMID- 26807568 TI - Functional Impairment and Physical Activity Adherence Among Gynecologic Cancer Survivors: A Population-Based Study. AB - OBJECTIVE: Adherence to physical activity guidelines after cancer diagnosis improves physical functioning. The purpose of this study was to estimate the prevalence of physical activity in a population-based sample of gynecologic cancer survivors (GCSs) and to examine the association between functional impairment and adherence to physical activity guidelines. METHODS: Using the 2009 Behavioral Risk Factor Surveillance System survey, we identified 5,015 GCSs aged 20 years or older who were 1 year or more after diagnosis. We used multinomial logistic regression with survey weighting to examine the association between functional impairment and adherence to physical activity guidelines (using 3 levels: sedentary, somewhat active, and meeting physical activity guidelines), controlling for demographic and clinical factors. RESULTS: We found that 55% of GCSs did not adhere to physical activity guidelines and that 38% reported functional impairment. Gynecologic cancer survivors with functional impairment were less likely to meet guidelines (adjusted odds ratio [AOR], 0.34; 95% confidence interval [CI], 0.25-0.47) or to be somewhat active (AOR, 0.43; 95% CI, 0.31-0.59) compared with those without impairment. Having more than high school education (AOR, 1.66; 95% CI, 1.15-2.40), fewer comorbidities (AOR, 0.55; 95% CI, 0.33-0.91), and not being obese (OR, 0.53; 95% CI, 0.36-0.77) were associated with meeting physical activity guidelines compared with being sedentary. CONCLUSIONS: Gynecologic cancer survivors do not meet physical activity guidelines and experience functional impairment, which is associated with lower adherence to physical activity recommendations. Prospective studies are needed to better elucidate the relation between functional impairment and physical activity. PMID- 26807569 TI - Intraoperative Gross Examination and Intraoperative Frozen Section in Patients With Endometrial Cancer for Detecting Deep Myometrial Invasion: A Systematic Review and Meta-analysis. AB - OBJECTIVE: The aim of this study was to perform a meta-analysis comparing diagnostic performance of intraoperative gross evaluation (IGE) and intraoperative frozen section (IFS) for the assessment of myometrial invasion in patients with endometrial cancer. METHODS: An extensive search was performed in several databases from January 1989 to May 2015. Eligibility criteria were studies using intraoperative gross evaluation or intraoperative frozen section to determine deep myometrial invasion in patients with endometrial cancer using the final histopathology report with reference standard. Quality was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Quality Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: Forty seven articles were identified. Of these, 35 studies were selected and included in the meta-analysis. A total of 6387 women were evaluated intraoperatively with any of the 2 methods mentioned. Pooled sensitivity and specificity for IGE were 71% (95% confidence interval [CI], 63%-77%) and 91% (95% CI, 89%-93%), respectively. Heterogeneity was found high for sensitivity (I2: 83.6%; Cochran Q: 79.4; P < 0.001) and moderate for specificity (I, 51.4%; Cochran Q, 29.8; P =0.01). Pooled sensitivity and specificity for IFS were 85% (95% CI, 81%-88%) and 97% (95% CI, 96%-98%), respectively. Heterogeneity was found moderate for sensitivity (I, 56.4%; Cochran Q, 45.9; P < 0.001) and high for specificity (I, 83.2%; Cochran Q, 118.9; P < 0.001). Both sensitivity (P = 0.0008) and specificity (P = 0.0021) were significantly higher for IFS compared to IGE. CONCLUSION: Intraoperative frozen section has better diagnostic performance than intraoperative gross evaluation for the intraoperative diagnosis of deep myometrial invasion in patients with endometrial cancer. PMID- 26807570 TI - The Hidden Costs of Financial Conflicts of Interest in Medicine. PMID- 26807571 TI - Global Expanded Nutrient Supply (GENuS) Model: A New Method for Estimating the Global Dietary Supply of Nutrients. AB - Insufficient data exist for accurate estimation of global nutrient supplies. Commonly used global datasets contain key weaknesses: 1) data with global coverage, such as the FAO food balance sheets, lack specific information about many individual foods and no information on micronutrient supplies nor heterogeneity among subnational populations, while 2) household surveys provide a closer approximation of consumption, but are often not nationally representative, do not commonly capture many foods consumed outside of the home, and only provide adequate information for a few select populations. Here, we attempt to improve upon these datasets by constructing a new model--the Global Expanded Nutrient Supply (GENuS) model--to estimate nutrient availabilities for 23 individual nutrients across 225 food categories for thirty-four age-sex groups in nearly all countries. Furthermore, the model provides historical trends in dietary nutritional supplies at the national level using data from 1961-2011. We determine supplies of edible food by expanding the food balance sheet data using FAO production and trade data to increase food supply estimates from 98 to 221 food groups, and then estimate the proportion of major cereals being processed to flours to increase to 225. Next, we estimate intake among twenty-six demographic groups (ages 20+, both sexes) in each country by using data taken from the Global Dietary Database, which uses nationally representative surveys to relate national averages of food consumption to individual age and sex-groups; for children and adolescents where GDD data does not yet exist, average calorie-adjusted amounts are assumed. Finally, we match food supplies with nutrient densities from regional food composition tables to estimate nutrient supplies, running Monte Carlo simulations to find the range of potential nutrient supplies provided by the diet. To validate our new method, we compare the GENuS estimates of nutrient supplies against independent estimates by the USDA for historical US nutrition and find very good agreement for 21 of 23 nutrients, though sodium and dietary fiber will require further improvement. PMID- 26807572 TI - Influence of Adjuvant Therapy in Cancer Survivors on Endothelial Function and Skeletal Muscle Deoxygenation. AB - The cardiotoxic effects of adjuvant cancer treatments (i.e., chemotherapy and radiation treatment) have been well documented, but the effects on peripheral cardiovascular function are still unclear. We hypothesized that cancer survivors i) would have decreased resting endothelial function; and ii) altered muscle deoxygenation response during moderate intensity cycling exercise compared to cancer-free controls. A total of 8 cancer survivors (~70 months post-treatment) and 9 healthy controls completed a brachial artery FMD test, an index of endothelial-dependent dilation, followed by an incremental exercise test up to the ventilatory threshold (VT) on a cycle ergometer during which pulmonary VO2 and changes in near-infrared spectroscopy (NIRS)-derived microvascular tissue oxygenation (TOI), total hemoglobin concentration ([Hb]total), and muscle deoxygenation ([HHb] ~ fractional O2 extraction) were measured. There were no significant differences in age, height, weight, and resting blood pressure between cancer survivors and control participants. Brachial artery FMD was similar between groups (P = 0.98). During exercise at the VT, TOI was similar between groups, but [Hb]total and [HHb] were significantly decreased in cancer survivors compared to controls (P < 0.01) The rate of change for TOI (DeltaTOIDelta/VO2) and [HHb] (Delta[HHb]/DeltaVO2) relative to DeltaVO2 were decreased in cancer survivors compared to controls (P = 0.02 and P = 0.03 respectively). In cancer survivors, a decreased skeletal muscle microvascular function was observed during moderate intensity cycling exercise. These data suggest that adjuvant cancer therapies have an effect on the integrated relationship between O2 extraction, VO2 and O2 delivery during exercise. PMID- 26807573 TI - Ursodeoxycholic Acid (UDCA) Exerts Anti-Atherogenic Effects by Inhibiting RAGE Signaling in Diabetic Atherosclerosis. AB - A naturally occurring bile acid, ursodeoxycholic acid (UDCA), is known to alleviate endoplasmic reticulum (ER) stress at the cellular level. However, the detailed action mechanisms of UDCA in atherosclerosis are not fully understood. In this study, we demonstrated whether UDCA exerts anti-atherogenic activity in diabetic atherosclerosis by targeting ER stress and "receptor for advanced glycation endproduct" (RAGE) signaling. UDCA markedly reduced ER stress, RAGE expression, and pro-inflammatory responses [including NF-kappaB activation and reactive oxygen species (ROS) production] induced in endothelial cells (ECs) by high glucose (HG). In particular, UDCA inhibited HG-induced ROS production by increasing the Nrf2 level. In macrophages, UDCA also blocked HG-induced RAGE and pro-inflammatory cytokine expression and inhibited foam cell formation via upregulation of the ATP-binding cassette (ABC) transporters, ABCA1 and ABCG1. In the diabetic mouse model, UDCA inhibited atheromatous plaque formation by decreasing ER stress, and the levels of RAGE and adhesion molecules. In conclusion, UDCA exerts an anti-atherogenic activity in diabetic atherosclerosis by targeting both ER stress and RAGE signaling. Our work implicates UDCA as a potential therapeutic agent for prevention or treatment of diabetic atherosclerosis. PMID- 26807574 TI - Correction: Feasibility of Elective Nodal Irradiation (ENI) and Involved Field Irradiation (IFI) in Radiotherapy for the Elderly Patients (Aged >= 70 Years) with Esophageal Squamous Cell Cancer: A Retrospective Analysis from a Single Institute. PMID- 26807575 TI - Whole-Genome Sequencing Analysis from the Chikungunya Virus Caribbean Outbreak Reveals Novel Evolutionary Genomic Elements. AB - BACKGROUND: Chikungunya virus (CHIKV), an alphavirus and member of the Togaviridae family, is capable of causing severe febrile disease in humans. In December of 2013 the Asian Lineage of CHIKV spread from the Old World to the Americas, spreading rapidly throughout the New World. Given this new emergence in naive populations we studied the viral genetic diversity present in infected individuals to understand how CHIKV may have evolved during this continuing outbreak. METHODOLOGY/PRINCIPLE FINDINGS: We used deep-sequencing technologies coupled with well-established bioinformatics pipelines to characterize the minority variants and diversity present in CHIKV infected individuals from Guadeloupe and Martinique, two islands in the center of the epidemic. We observed changes in the consensus sequence as well as a diverse range of minority variants present at various levels in the population. Furthermore, we found that overall diversity was dramatically reduced after single passages in cell lines. Finally, we constructed an infectious clone from this outbreak and identified a novel 3' untranslated region (UTR) structure, not previously found in nature, that led to increased replication in insect cells. CONCLUSIONS/SIGNIFICANCE: Here we preformed an intrahost quasispecies analysis of the new CHIKV outbreak in the Caribbean. We identified novel variants present in infected individuals, as well as a new 3'UTR structure, suggesting that CHIKV has rapidly evolved in a short period of time once it entered this naive population. These studies highlight the need to continue viral diversity surveillance over time as this epidemic evolves in order to understand the evolutionary potential of CHIKV. PMID- 26807576 TI - Association between Anti-Ganglionic Nicotinic Acetylcholine Receptor (gAChR) Antibodies and HLA-DRB1 Alleles in the Japanese Population. AB - BACKGROUND/AIMS: Anti-ganglionic nicotinic acetylcholine receptor (gAChR) antibodies are observed in autoimmune diseases, as well as in patients with autoimmune autonomic ganglionopathy. However, the genetic background of anti gAChR antibodies is unclear. Here, we investigated HLA alleles in autoimmune hepatitis (AIH) patients with or without anti-gAChR antibodies. METHODOLOGY/PRINCIPAL FINDINGS: Genomic DNA from 260 patients with type-1 autoimmune hepatitis (AIH) were genotyped for HLA-A, B, DRB1, and DQB1 loci. Anti gAChR antibodies in the sera form AIH patients were measured using the luciferase immunoprecipitation system, and examined allelic association in patients with or without anti-gAChR antibodies. METHODOLOGY/ METHODS: We detected anti-alpha3 or beta4 gAChR antibodies in 11.5% (30/260) of patients with AIH. Among AIH patients there was no significant association between HLA-A, B DQB1 alleles and the positivity for anti-gAChR antibodies. Whereas the HLA-DRB1*0403 allele showed a significantly increased frequency in AIH patients with anti-gAChR antibodies compared with those without anti-gAChR antibodies. CONCLUSIONS/SIGNIFICANCE: The frequency of the HLA-DRB1*0403 allele differed among Japanese patients with AIH according to the presence or absence of anti-gAChR antibodies. Our findings suggest that particular HLA class II molecules might control the development of anti-gAChR antibodies in the autoimmune response to gAChR. PMID- 26807577 TI - Patient and System-Related Delays of Emergency Medical Services Use in Acute ST Elevation Myocardial Infarction: Results from the Third Gulf Registry of Acute Coronary Events (Gulf RACE-3Ps). AB - BACKGROUND: Little is known about Emergency Medical Services (EMS) use and pre hospital triage of patients with acute ST-elevation myocardial infarction (STEMI) in Arabian Gulf countries. METHODS: Clinical arrival and acute care within 24 h of STEMI symptom onset were compared between patients transferred by EMS (Red Crescent and Inter-Hospital) and those transferred by non-EMS means. Data were retrieved from a prospective registry of 36 hospitals in 6 Arabian Gulf countries, from January 2014 to January 2015. RESULTS: We enrolled 2,928 patients; mean age, 52.7 (SD +/-11.8) years; 90% men; and 61.7% non-Arabian Gulf citizens. Only 753 patients (25.7%) used EMS; which was mostly via Inter-Hospital EMS (22%) rather than direct transfer from the scene to the hospital by the Red Crescent (3.7%). Compared to the non-EMS group, the EMS group was more likely to arrive initially at a primary or secondary health care facility; thus, they had longer median symptom-onset-to-emergency department arrival times (218 vs. 158 min; p?.001); they were more likely to receive primary percutaneous coronary interventions (62% vs. 40.5%, p = 0.02); they had shorter door-to-needle times (38 vs. 42 min; p = .04); and shorter door-to-balloon times (47 vs. 83 min; p?.001). High EMS use was independently predicted mostly by primary/secondary school educational levels and low or moderate socioeconomic status. Low EMS use was predicted by a history of angina and history of percutaneous coronary intervention. The groups had similar in-hospital deaths and outcomes. CONCLUSION: Most acute STEMI patients in the Arabian Gulf region did not use EMS services. Improving Red Crescent infrastructure, establishing integrated STEMI networks, and launching educational public campaigns are top health care system priorities. PMID- 26807578 TI - Dynamic Frequency Analyses of Lower Extremity Muscles during Sit-To-Stand Motion for the Patients with Knee Osteoarthritis. AB - OBJECTIVE: Muscle activities during the sit-to-stand motion (STS) are characterized by coordinated movements between hip extensors and knee extensors. However, previous reports regarding the STS and lower extremity muscle activities have focused on some quantitative assessment, but little qualitative research. This study aimed to examine the muscle activities of the lower extremity both quantitatively and qualitatively. METHODS: Study participants included 13 patients with knee osteoarthritis (knee OA) and 11 age-matched asymptomatic controls. The task was STS from a chair with a height-adjustable seat. EMG activities were acquired using surface electromyogram. The root mean square signals normalized as a percentage of maximum voluntary isometric contraction values (RMS%MVC) and the mean power frequency (MPF) were calculated. RESULTS: During STS, knee OA patients had increased RMS%MVC of the vastus medialis and raised MPF of the rectus femoris before buttocks-off. CONCLUSION: These findings suggest that STS of knee OA patients not only increased relative muscle activity of the vastus medialis, but also enlisted the rectus femoris in knee extension to improve muscle contraction force by activating more type II fibers to accomplish buttocks-off. PMID- 26807579 TI - Improving Estimations of Spatial Distribution of Soil Respiration Using the Bayesian Maximum Entropy Algorithm and Soil Temperature as Auxiliary Data. AB - Soil respiration inherently shows strong spatial variability. It is difficult to obtain an accurate characterization of soil respiration with an insufficient number of monitoring points. However, it is expensive and cumbersome to deploy many sensors. To solve this problem, we proposed employing the Bayesian Maximum Entropy (BME) algorithm, using soil temperature as auxiliary information, to study the spatial distribution of soil respiration. The BME algorithm used the soft data (auxiliary information) effectively to improve the estimation accuracy of the spatiotemporal distribution of soil respiration. Based on the functional relationship between soil temperature and soil respiration, the BME algorithm satisfactorily integrated soil temperature data into said spatial distribution. As a means of comparison, we also applied the Ordinary Kriging (OK) and Co Kriging (Co-OK) methods. The results indicated that the root mean squared errors (RMSEs) and absolute values of bias for both Day 1 and Day 2 were the lowest for the BME method, thus demonstrating its higher estimation accuracy. Further, we compared the performance of the BME algorithm coupled with auxiliary information, namely soil temperature data, and the OK method without auxiliary information in the same study area for 9, 21, and 37 sampled points. The results showed that the RMSEs for the BME algorithm (0.972 and 1.193) were less than those for the OK method (1.146 and 1.539) when the number of sampled points was 9 and 37, respectively. This indicates that the former method using auxiliary information could reduce the required number of sampling points for studying spatial distribution of soil respiration. Thus, the BME algorithm, coupled with soil temperature data, can not only improve the accuracy of soil respiration spatial interpolation but can also reduce the number of sampling points. PMID- 26807580 TI - Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis. AB - The Drosophila testis is a well-established system for studying stem cell self renewal and competition. In this tissue, the niche supports two stem cell populations, germ line stem cells (GSCs), which give rise to sperm, and somatic stem cells called cyst stem cells (CySCs), which support GSCs and their descendants. It has been established that CySCs compete with each other and with GSCs for niche access, and mutations have been identified that confer increased competitiveness to CySCs, resulting in the mutant stem cell and its descendants outcompeting wild type resident stem cells. Socs36E, which encodes a negative feedback inhibitor of the JAK/STAT pathway, was the first identified regulator of niche competition. The competitive behavior of Socs36E mutant CySCs was attributed to increased JAK/STAT signaling. Here we show that competitive behavior of Socs36E mutant CySCs is due in large part to unbridled Mitogen Activated Protein Kinase (MAPK) signaling. In Socs36E mutant clones, MAPK activity is elevated. Furthermore, we find that clonal upregulation of MAPK in CySCs leads to their outcompetition of wild type CySCs and of GSCs, recapitulating the Socs36E mutant phenotype. Indeed, when MAPK activity is removed from Socs36E mutant clones, they lose their competitiveness but maintain self-renewal, presumably due to increased JAK/STAT signaling in these cells. Consistently, loss of JAK/STAT activity in Socs36E mutant clones severely impairs their self-renewal. Thus, our results enable the genetic separation of two essential processes that occur in stem cells. While some niche signals specify the intrinsic property of self-renewal, which is absolutely required in all stem cells for niche residence, additional signals control the ability of stem cells to compete with their neighbors. Socs36E is node through which these processes are linked, demonstrating that negative feedback inhibition integrates multiple aspects of stem cell behavior. PMID- 26807581 TI - Role of Proteolipid Protein in HSV-1 Entry in Oligodendrocytic Cells. AB - Herpes simplex virus type 1 (HSV-1) has the ability to enter many different hosts and cell types by several strategies. This highly prevalent alphaherpesvirus can enter target cells using different receptors and different pathways: fusion at a neutral pH, low-pH-dependent and low-pH-independent endocytosis. Several cell receptors for viral entry have been described, but several observations suggest that more receptors for HSV-1 might exist. In this work, we propose a novel role for the proteolipid protein (PLP) in HSV-1 entry into the human oligodendrocytic cell line HOG. Cells transfected with PLP-EGFP showed an increase in susceptibility to HSV-1. Furthermore, the infection of HOG and HOG-PLP transfected cells with the R120vGF virus--unable to replicate in ICP4-defficient cells--showed an increase in viral signal in HOG-PLP, suggesting a PLP involvement in viral entry. In addition, a mouse monoclonal antibody against PLP drastically inhibited HSV-1 entry into HOG cells. PLP and virions colocalized in confocal immunofluorescence images, and in electron microscopy images, which suggest that PLP acts at the site of entry into HOG cells. Taken together these results suggest that PLP may be involved in HSV-1 entry in human oligodendrocytic cells. PMID- 26807582 TI - Giving Is Nicer than Taking: Preschoolers Reciprocate Based on the Social Intentions of the Distributor. AB - Recent research has found that even preschoolers give more resources to others who have previously given resources to them, but the psychological bases of this reciprocity are unknown. In our study, a puppet distributed resources between herself and a child by taking some from a pile in front of the child or else by giving some from a pile in front of herself. Although the resulting distributions were identical, three- and five-year-olds reciprocated less generously when the puppet had taken rather than given resources. This suggests that children's judgments about resource distribution are more about the social intentions of the distributor and the social framing of the distributional act than about the amount of resources obtained. In order to rule out that the differences in the children's reciprocal behavior were merely due to experiencing gains and losses, we conducted a follow-up study. Here, three- and-five year olds won or lost resources in a lottery draw and could then freely give or take resources to/from a puppet, respectively. In this study, they did not respond differently after winning vs. losing resources. PMID- 26807583 TI - Corticospinal Excitability of Trunk Muscles during Different Postural Tasks. AB - Evidence suggests that the primary motor cortex (M1) is involved in both voluntary, goal-directed movements and in postural control. Trunk muscles are involved in both tasks, however, the extent to which M1 controls these muscles in trunk flexion/extension (voluntary movement) and in rapid shoulder flexion (postural control) remains unclear. The purpose of this study was to investigate this question by examining excitability of corticospinal inputs to trunk muscles during voluntary and postural tasks. Twenty healthy adults participated. Transcranial magnetic stimulation was delivered to the M1 to examine motor evoked potentials (MEPs) in the trunk muscles (erector spinae (ES) and rectus abdominis (RA)) during dynamic shoulder flexion (DSF), static shoulder flexion (SSF), and static trunk extension (STE). The level of background muscle activity in the ES muscles was matched across tasks. MEP amplitudes in ES were significantly larger in DSF than in SSF or in STE; however, this was not observed for RA. Further, there were no differences in levels of muscle activity in RA between tasks. Our findings reveal that corticospinal excitability of the ES muscles appears greater during dynamic anticipatory posture-related adjustments than during static tasks requiring postural (SSF) and goal-directed voluntary (STE) activity. These results suggest that task-oriented rehabilitation of trunk muscles should be considered for optimal transfer of therapeutic effect to function. PMID- 26807584 TI - Correlates of HIV Testing among Female Sex Workers in Iran: Findings of a National Bio-Behavioural Surveillance Survey. AB - INTRODUCTION: Female sex workers (FSWs) are the second most affected population by HIV in Iran. However, their HIV testing practices are poorly understood. The aim of this study was to investigate testing and its associated factors among HIV negative FSWs. MATERIALS AND METHODS: Using facility based sampling, 1005 FSWs were recruited in 14 cities of Iran in 2010. Biological and survey data were collected through dried blood spot testing and standardized risk assessment questionnaire, respectively. In this paper, the prevalence of HIV testing and its correlates were explored among 714 HIV-negative FSWs using descriptive statistics and logistic regression models. RESULTS: Overall 65.4% had not tested in the past year. Only 27.5% had tested in the past year and received their results. FSWs who perceived themselves at risk of HIV (Adjusted Odds Ratio (AOR) = 8.35, 95% CI: 1.46, 47.6), had received free condom during past year (AOR = 3.90, 95% CI: 1.67, 9.14), started sex work at an older age (AOR18-24 = 2.83, 95% CI: 1.14, 7.0; AOR >24 = 2.76, 95% CI: 1.11, 6.84), and knew an HIV testing site (AOR = 5.67, 95% CI: 2.60, 12.4) had a significantly higher chance of having a recent HIV test result. CONCLUSIONS: Less than one third of FSWs in Iran knew their recent HIV status. Interventions to help FSWs evaluate their potential risk for HIV and integrate HIV testing services in condom distribution programs, could be viable strategies in increasing HIV testing uptake among FSWs. Health policy makers should also try to de-stigmatize HIV testing, identify the barriers to HIV testing, and make HIV testing sites more visible to FSWs. PMID- 26807585 TI - Azilsartan Improves Salt Sensitivity by Modulating the Proximal Tubular Na+-H+ Exchanger-3 in Mice. AB - A potent angiotensin II type-1 receptor blocker, azilsartan, has been reported to reduce blood pressure more effectively than candesartan. Interestingly, azilsartan can also restore the circadian rhythm of blood pressure. We hypothesized that azilsartan could also improve salt sensitivity; thus, we examined the effect of azilsartan on sodium handling in renal tubules. Subtotal nephrectomized C57BL/6 mice received azilsartan (1.0 mg/kg/day), candesartan (0.3 mg/kg/day), or vehicle via the oral route in conjunction with a normal- (0.3%) or high-salt (8.0%) diet. Two weeks later, the azilsartan group showed significantly lower blood pressure during the light period than the candesartan and vehicle groups (azilsartan: 103.1 +/- 1.0; candesartan: 111.7 +/- 2.7; vehicle: 125.5 +/- 2.5 mmHg; P < 0.05; azilsartan or candesartan vs. vehicle). The azilsartan group also showed higher urinary fractional excretion of sodium during the dark period than the candesartan and vehicle groups (azilsartan: 21.37 +/- 3.69%; candesartan: 14.17 +/- 1.42%; vehicle: 13.85 +/- 5.30%; P < 0.05 azilsartan vs. candesartan or vehicle). A pressure-natriuresis curve demonstrated that azilsartan treatment restored salt sensitivity. Immunofluorescence and western blotting showed lower levels of Na+-H+ exchanger-3 (NHE3) protein (the major sodium transporter in renal proximal tubules) in the azilsartan group, but not in the candesartan or vehicle groups. However, azilsartan did not affect NHE3 transcription levels. Interestingly, we did not observe increased expression of downstream sodium transporters, which would have compensated for the increased flow of sodium and water due to non-absorption by NHE3. We also confirmed the mechanism stated above using cultured opossum kidney proximal tubular cells. Results revealed that a proteasomal inhibitor (but not a lysosomal inhibitor) blocked the azilsartan-induced decrease in NHE3 protein expression, suggesting that azilsartan increases NHE3 ubiquitination. In conclusion, azilsartan (but not candesartan) improved salt sensitivity possibly by decreasing NHE3 expression via ubiquitin-proteasomal degradation. PMID- 26807586 TI - Aqueous Angiography: Real-Time and Physiologic Aqueous Humor Outflow Imaging. AB - PURPOSE: Trabecular meshwork (TM) bypass surgeries attempt to enhance aqueous humor outflow (AHO) to lower intraocular pressure (IOP). While TM bypass results are promising, inconsistent success is seen. One hypothesis for this variability rests upon segmental (non-360 degrees uniform) AHO. We describe aqueous angiography as a real-time and physiologic AHO imaging technique in model eyes as a way to simulate live AHO imaging. METHODS: Pig (n = 46) and human (n = 6) enucleated eyes were obtained, orientated based upon inferior oblique insertion, and pre-perfused with balanced salt solution via a Lewicky AC maintainer through a 1mm side-port. Fluorescein (2.5%) was introduced intracamerally at 10 or 30 mm Hg. With an angiographer, infrared and fluorescent (486 nm) images were acquired. Image processing allowed for collection of pixel information based on intensity or location for statistical analyses. Concurrent OCT was performed, and fixable fluorescent dextrans were introduced into the eye for histological analysis of angiographically active areas. RESULTS: Aqueous angiography yielded high quality images with segmental patterns (p<0.0001; Kruskal-Wallis test). No single quadrant was consistently identified as the primary quadrant of angiographic signal (p = 0.06-0.86; Kruskal-Wallis test). Regions of high proximal signal did not necessarily correlate with regions of high distal signal. Angiographically positive but not negative areas demonstrated intrascleral lumens on OCT images. Aqueous angiography with fluorescent dextrans led to their trapping in AHO pathways. CONCLUSIONS: Aqueous angiography is a real-time and physiologic AHO imaging technique in model eyes. PMID- 26807588 TI - Correction: Pyocycanin, a Contributory Factor in Haem Acquisition and Virulence Enhancement of Porphyromonas gingivalis in the Lung. PMID- 26807587 TI - Novel Neuroprotective Multicomponent Therapy for Amyotrophic Lateral Sclerosis Designed by Networked Systems. AB - Amyotrophic Lateral Sclerosis is a fatal, progressive neurodegenerative disease characterized by loss of motor neuron function for which there is no effective treatment. One of the main difficulties in developing new therapies lies on the multiple events that contribute to motor neuron death in amyotrophic lateral sclerosis. Several pathological mechanisms have been identified as underlying events of the disease process, including excitotoxicity, mitochondrial dysfunction, oxidative stress, altered axonal transport, proteasome dysfunction, synaptic deficits, glial cell contribution, and disrupted clearance of misfolded proteins. Our approach in this study was based on a holistic vision of these mechanisms and the use of computational tools to identify polypharmacology for targeting multiple etiopathogenic pathways. By using a repositioning analysis based on systems biology approach (TPMS technology), we identified and validated the neuroprotective potential of two new drug combinations: Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine. In addition, we estimated their molecular mechanisms of action in silico and validated some of these results in a well-established in vitro model of amyotrophic lateral sclerosis based on cultured spinal cord slices. The results verified that Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine promote neuroprotection of motor neurons and reduce microgliosis. PMID- 26807589 TI - A Single-Nucleotide Polymorphism in ABCC4 Is Associated with Tenofovir-Related Beta2-Microglobulinuria in Thai Patients with HIV-1 Infection. AB - BACKGROUND: In Thailand, the combined generic anti-retroviral drug stavudine/lamivudine/nevirapine (d4T/3TC/NVP) has been used to treat human immunodeficiency virus (HIV)-infected individuals since 2001. Due to relatively frequent adverse effects, d4T gradually has been replaced with tenofovir disoproxil fumarate (TDF). Although the frequency of adverse drug effects with TDF is lower than that with d4T, TDF is known to induce kidney dysfunction, especially in the proximal tubules. It has been reported that renal tubular transporters, including members of the multi-drug resistant (MDR) protein family, are implicated in tenofovir extrusion and may, therefore, confer susceptibility to TDF-induced kidney tubular dysfunction (KTD). We have explored the association between KTD and polymorphisms in genes that encode adenosine triphosphate-binding cassette (ABC)-type MDRs. METHODS: HIV-infected patients receiving TDF-containing antiretroviral regimens for at least one year were enrolled in the study. The levels of beta2-microglobulin in urine and creatinine (Cr) were measured. Three single-nucleotide polymorphisms, ABCC2 C-24T (rs717620), ABCC2 G1429A (rs2273697), and ABCC4 T4976C (rs1059751), were analyzed using TaqMan SNP genotyping assays. RESULTS: A total of 273 HIV-infected patients were recruited. The median number of years of TDF treatment was 5.04 with interquartile range (IQR) of 3.9-6.7. Despite the length of treatment with TDF, 98.5% patients maintained an estimated glomerular filtration rate (eGFR) of >60 mL/min as calculated by the CKD-EPI formula. Fifty-four patients (19.8%) showed beta2 microglobulinuria (median 2636 MUg/g Cr with IQR of 1519-13197 MUg/g Cr). The allele frequency of ABCC4 T4976C among those 54 patients was 0.602, compared to 0.475 among the 219 remaining patients (p = 0.018). CONCLUSIONS: Approximately 20% of HIV-infected patients receiving TDF showed beta2-microglobulinuria. The C allele at position 4976 of the ABCC4 gene was associated with beta2 microglobulinuria in this population. This polymorphism may help to identify patients at greater risk for developing TDF-associated KTD. PMID- 26807590 TI - Cardiac Dysfunction in the BACHD Mouse Model of Huntington's Disease. AB - While Huntington's disease (HD) is classified as a neurological disorder, HD patients exhibit a high incidence of cardiovascular events leading to heart failure and death. In this study, we sought to better understand the cardiovascular phenotype of HD using the BACHD mouse model. The age-related decline in cardiovascular function was assessed by echocardiograms, electrocardiograms, histological and microarray analysis. We found that structural and functional differences between WT and BACHD hearts start at 3 months of age and continue throughout life. The aged BACHD mice develop cardiac fibrosis and ultimately apoptosis. The BACHD mice exhibited adaptive physiological changes to chronic isoproterenol treatment; however, the medication exacerbated fibrotic lesions in the heart. Gene expression analysis indicated a strong tilt toward apoptosis in the young mutant heart as well as changes in genes involved in cellular metabolism and proliferation. With age, the number of genes with altered expression increased with the large changes occurring in the cardiovascular disease, cellular metabolism, and cellular transport clusters. The BACHD model of HD exhibits a number of changes in cardiovascular function that start early in the disease progress and may provide an explanation for the higher cardiovascular risk in HD. PMID- 26807592 TI - Telomeres open a window on stem cell division. AB - Measuring the length distribution of telomeres can reveal information about biological processes that are otherwise difficult to analyze experimentally. PMID- 26807593 TI - A Long-Term View on Perovskite Optoelectronics. AB - Recently, metal halide perovskite materials have become an exciting topic of research for scientists of a wide variety of backgrounds. Perovskites have found application in many fields, starting from photovoltaics and now also making an impact in light-emitting applications. This new class of materials has proven so interesting since it can be easily solution processed while exhibiting materials properties approaching the best inorganic optoelectronic materials such as GaAs and Si. In photovoltaics, in only 3 years, efficiencies have rapidly increased from an initial value of 3.8% to over 20% in recent reports for the commonly employed methylammonium lead iodide (MAPI) perovskite. The first light emitting diodes and light-emitting electrochemical cells have been developed already exhibiting internal quantum efficiencies exceeding 15% for the former and tunable light emission spectra. Despite their processing advantages, perovskite optoelectronic materials suffer from several drawbacks that need to be overcome before the technology becomes industrially relevant and hence achieve long-term application. Chief among these are the sensitivity of the structure toward moisture and crystal phase transitions in the device operation regime, unreliable device performance dictated by the operation history of the device, that is, hysteresis, the inherent toxicity of the structure, and the high cost of the employed charge selective contacts. In this Account, we highlight recent advances toward the long-term viability of perovskite photovoltaics. We identify material decomposition routes and suggest strategies to prevent damage to the structure. In particular, we focus on the effect of moisture upon the structure and stabilization of the material to avoid phase transitions in the solar cell operating range. Furthermore, we show strategies to achieve low-cost chemistries for the development of hole transporters for perovskite solar cells, necessary to be able to compete with other established technologies. Additionally, we explore the application of perovskite materials in optoelectronic applications. We show that perovskite materials can function efficiently both as a film in light emitting diodes and also in the form of nanoparticles in light-emitting electrochemical cells. Perovskite materials have indeed a very bright future. PMID- 26807591 TI - Clostridium perfringens Delta-Toxin Induces Rapid Cell Necrosis. AB - Clostridium perfringens delta-toxin is a beta-pore-forming toxin and a putative pathogenic agent of C. perfringens types B and C. However, the mechanism of cytotoxicity of delta-toxin remains unclear. Here, we investigated the mechanisms of cell death induced by delta-toxin in five cell lines (A549, A431, MDCK, Vero, and Caco-2). All cell lines were susceptible to delta-toxin. The toxin caused rapid ATP depletion and swelling of the cells. Delta-toxin bound and formed oligomers predominantly in plasma membrane lipid rafts. Destruction of the lipid rafts with methyl beta-cyclodextrin inhibited delta-toxin-induced cytotoxicity and ATP depletion. Delta-toxin caused the release of carboxyfluorescein from sphingomyelin-cholesterol liposomes and formed oligomers; toxin binding to the liposomes declined with decreasing cholesterol content in the liposomes. Flow cytometric assays with annexin V and propidium iodide revealed that delta-toxin treatment induced an elevation in the population of annexin V-negative and propidium iodide-positive cells. Delta-toxin did not cause the fragmentation of DNA or caspase-3 activation. Furthermore, delta-toxin caused damage to mitochondrial membrane permeability and cytochrome c release. In the present study, we demonstrate that delta-toxin produces cytotoxic activity through necrosis. PMID- 26807594 TI - Palladium-Catalyzed Carbonylative alpha-Arylation of tert-Butyl Cyanoacetate with (Hetero)aryl Bromides. AB - A three-component coupling protocol has been developed for the generation of 3 oxo-3-(hetero)arylpropanenitriles via a carbonylative palladium-catalyzed alpha arylation of tert-butyl 2-cyanoacetates with (hetero)aryl bromides followed by an acid-mediated decarboxylation step. Through the combination of only a stoichiometric loading of carbon monoxide and mild basic reaction conditions such as MgCl2 and dicyclohexylmethylamine for the deprotonation step, an excellent functional group tolerance was ensured for the methodology. Through the use of (13)C-labeled carbon monoxide generated from (13)COgen, the corresponding (13)C isotopically labeled beta-ketonitriles were obtained, and these products could subsequently be converted into cyanoalkynes and 3-cyanobenzofurans with site specific (13)C-isotope labeling. PMID- 26807595 TI - The Effect of Milk Constituents and Crowding Agents on Amyloid Fibril Formation by kappa-Casein. AB - When not incorporated into the casein micelle, kappa-casein, a major milk protein, rapidly forms amyloid fibrils at physiological pH and temperature. In this study, the effects of milk components (calcium, lactose, lipids, and heparan sulfate) and crowding agents on reduced and carboxymethylated (RCM) kappa-casein fibril formation was investigated using far-UV circular dichroism spectroscopy, thioflavin T binding assays, and transmission electron microscopy. Longer-chain phosphatidylcholine lipids, which form the lining of milk ducts and milk fat globules, enhanced RCM kappa-casein fibril formation irrespective of whether the lipids were in a monomeric or micellar state, whereas shorter-chain phospholipids and triglycerides had little effect. Heparan sulfate, a component of the milk fat globule membrane and catalyst of amyloid deposition in extracellular tissue, had little effect on the kinetics of RCM kappa-casein fibril formation. Major nutritional components such as calcium and lactose also had no significant effect. Macromolecular crowding enhances protein-protein interactions, but in contrast to other fibril-forming species, the extent of RCM kappa-casein fibril formation was reduced by the presence of a variety of crowding agents. These data are consistent with a mechanism of kappa-casein fibril formation in which the rate-determining step is dissociation from the oligomer to give the highly amyloidogenic monomer. We conclude that the interaction of kappa-casein with membrane-associated phospholipids along its secretory pathway may contribute to the development of amyloid deposits in mammary tissue. However, the formation of spherical oligomers such as casein micelles is favored over amyloid fibrils in the crowded environment of milk, within which the occurrence of amyloid fibrils is low. PMID- 26807596 TI - Enhanced Collective Magnetic Properties in 2D Monolayers of Iron Oxide Nanoparticles Favored by Local Order and Local 1D Shape Anisotropy. AB - Magnetic nanoparticle arrays represent a very attractive research field because their collective properties can be efficiently modulated as a function of the structure of the assembly. Nevertheless, understanding the way dipolar interactions influence the intrinsic magnetic properties of nanoparticles still remains a great challenge. In this study, we report on the preparation of 2D assemblies of iron oxide nanoparticles as monolayers deposited onto substrates. Assemblies have been prepared by using the Langmuir-Blodgett technique and the SAM assisted assembling technique combined to CuAAC "click" reaction. These techniques afford to control the formation of well-defined monolayers of nanoparticles on large areas. The LB technique controls local ordering of nanoparticles, while adjusting the kinetics of CuAAC "click" reaction strongly affects the spatial arrangement of nanoparticles in monolayers. Fast kinetics favor disordered assemblies while slow kinetics favor the formation of chain-like structures. Such anisotropic assemblies are induced by dipolar interactions between nanoparticles as no magnetic field is applied and no solvent evaporation is performed. The collective magnetic properties of monolayers are studied as a function of average interparticle distance, local order and local shape anisotropy. We demonstrate that local control on spatial arrangement of nanoparticles in monolayers significantly strengthens dipolar interactions which enhances collective properties and results in possible super ferromagnetic order. PMID- 26807597 TI - Distributive O-GlcNAcylation on the Highly Repetitive C-Terminal Domain of RNA Polymerase II. AB - O-GlcNAcylation is a nutrient-responsive glycosylation that plays a pivotal role in transcriptional regulation. Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. One approach to understanding the function of glycosylated Pol II is to determine the mechanism of dynamic O GlcNAcylation on the CTD. Here, we discovered that the Pol II CTD can be extensively O-GlcNAcylated in vitro and in cells. Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N terminal domain of O-GlcNAc transferase (OGT). Under conditions of saturated sugar donor, we monitored the attachment of more than 20 residues of O-GlcNAc to the full-length CTD. Surprisingly, glycosylation on the periodic CTD follows a distributive mechanism, resulting in highly heterogeneous glycoforms. Our data suggest that initial O-GlcNAcylation can take place either on the proximal or on the distal region of the CTD, and subsequent glycosylation occurs similarly over the entire CTD with nonuniform distributions. Moreover, removal of O-GlcNAc from glycosylated CTD is also distributive and is independent of O-GlcNAcylation level. Our results suggest that O-GlcNAc cycling enzymes can employ a similar mechanism to react with other protein substrates on multiple sites. Distributive O-GlcNAcylation on Pol II provides another regulatory mechanism of transcription in response to fluctuating cellular conditions. PMID- 26807598 TI - A Highly-Durable CO-Tolerant Poly(vinylphosphonic acid)-Coated Electrocatalyst Supported on a Nanoporous Carbon. AB - For direct methanol fuel cells (DMFCs) to be commercialized, the durability of the anodic electrocatalyst needs to be highly considered, especially under high temperature and methanol concentration conditions. Low durability caused by carbon corrosion as well as carbon monoxide (CO) poisoning of the platinum nanoparticles (Pt-NP) leads to a decrease in active Pt-NPs and increases inactive Pt-NPs covered by CO species. In this study, we deposited Pt-NPs on poly[2,2' (2,6-pyridine)-5,5'-bibenzimidazole] (PyPBI)-wrapped nanoporous carbon (NanoPC) and coated the as-synthesized electrocatalyst with poly(vinylphosphonic acid) (PVPA). The durability of the as-synthesized NanoPC/PyPBI/Pt/PVPA was tested in 0.1 M HClO4 electrolyte at 60 degrees C by cycling the potential from 1.0 to 1.5 V relative to RHE, and the results indicated that NanoPC/PyPBI/Pt/PVPA showed ~5 times better durability relative to that of the commercial CB/Pt. The methanol oxidation reaction (MOR) of the electrocatalyst was tested before and after the potential cycling in the presence of 4 or 8 M methanol at 60 degrees C and found that the CO tolerance of the electrocatalyst was ~3 times higher than that of the commercial CB/Pt. Such a higher CO tolerance is due to the coating of the PVPA, which was proven by an EDX mapping measurement. The NanoPC/PyPBI/Pt/PVPA showed a high durability and CO tolerance under high temperature and high methanol concentration conditions, indicating that the electrocatalyst could be used in real fuel applications. PMID- 26807600 TI - Anisotropic Growth of TiO2 onto Gold Nanorods for Plasmon-Enhanced Hydrogen Production from Water Reduction. AB - Plasmonic metal/semiconductor heterostructures show promise for visible-light driven photocatalysis. Gold nanorods (AuNRs) semi-coated with TiO2 are expected to be ideally structured systems for hydrogen evolution. Synthesizing such structures by wet-chemistry methods, however, has proved challenging. Here we report the bottom-up synthesis of AuNR/TiO2 nanodumbbells (NDs) with spatially separated Au/TiO2 regions, whose structures are governed by the NRs' diameter, and the higher curvature and lower density of CnTAB surfactant at the NRs' tips than on their lateral surfaces, as well as the morphology's dependence on concentration, and alkyl chain length of CnTAB. The NDs show plasmon-enhanced H2 evolution under visible and near-infrared light. PMID- 26807599 TI - High Affinity Macrocycle Threading by a Near-Infrared Croconaine Dye with Flanking Polymer Chains. AB - Croconaine dyes have narrow and intense absorption bands at ~800 nm, very weak fluorescence, and high photostabilities, which combine to make them very attractive chromophores for absorption-based imaging or laser heating technologies. The physical supramolecular properties of croconaine dyes have rarely been investigated, especially in water. This study focuses on a molecular threading process that encapsulates a croconaine dye inside a tetralactam macrocycle in organic or aqueous solvent. Macrocycle association and rate constant data are reported for a series of croconaine structures with different substituents attached to the ends of the dye. The association constants were highest in water (Ka ~ 10(9) M(-1)), and the threading rate constants (kon) increased in the solvent order H2O > MeOH > CHCl3. Systematic variation of croconaine substituents located just outside the croconaine/macrocycle complexation interface hardly changed Ka but had a strong influence on kon. A croconaine dye with N-propyl groups at each end of the structure exhibited a desirable mixture of macrocycle threading properties; that is, there was rapid and quantitative croconaine/macrocycle complexation at relatively high concentrations in water, and no dissociation of the preassembled complex when it was diluted into a solution of fetal bovine serum, even after laser-induced photothermal heating of the solution. The combination of favorable near-infrared absorption properties and tunable mechanical stability makes threaded croconaine/macrocycle complexes very attractive as molecular probes or as supramolecular composites for various applications in absorption-based imaging or photothermal therapy. PMID- 26807601 TI - Is matching ruthenium with dithiocarbamato ligands a potent chemotherapeutic weapon in oncology? AB - In the last years, several metal-based compounds have been designed and biologically investigated worldwide in order to obtain chemotherapeutics with a better toxicological profile and comparable or higher antiblastic activity than the clinically-established platinum-based drugs. In this context, researchers have addressed their attention to alternative nonplatinum derivatives able to maximize the anticancer activity of the new drugs and to minimize the side effects. Among them, a number of ruthenium complexes have been developed, including the compounds NAMI-A and KP1019, now in clinical trials. Here, we report the results collected so far for a particular class of ruthenium complexes - the ruthenium(II/III)-dithiocarbamates - which proved more potent than cisplatin in vitro, even at nanomolar concentrations, against a wide panel of human tumor cell lines. PMID- 26807602 TI - Lost in translation? Ten years of development of histone deacetylase inhibitors in acute myeloid leukemia and myelodysplastic syndromes. AB - INTRODUCTION: Epigenetic changes and mutations in epigenetic modifiers characterize and likely drive many cases of acute myeloid leukemia and myelodysplastic syndrome. Development of DNA methyltransferase inhibitors has been most successful in these diseases. While many epigenetic marks are potential targets of cancer therapies, histone deacetylase inhibitors (HDACi) have undergone the most advanced development to date. AREA COVERED: In this review, the authors describe and discuss the biology and the clinical results of HDAC inhibitors in the settings of myeloid malignancies. EXPERT OPINION: While significant results have been achieved in lymphoma and myeloma, efficacy remains limited in myeloid malignancies for both single agent and HDACi based combination regimens. The redundancy and the pleiotropic activity of HDACi (on both histone and non-histone proteins) are key factors that have limited to date the selection of patients and the design of robust biomarkers. Recent advances in biology (mechanisms of resistance, immunology) and the design of a more specific third generation of HDACi are two important features that will drive the future clinical development of HDACi in myeloid malignancies. PMID- 26807603 TI - Onychomycosis - a small step for quality of care. AB - Onychomycosis is a fungal infection of the nail unit, representing the most common nail disorder and accounting for 50% all nail diseases. Unfortunately, many patients are mismanaged, as physicians routinely treat onychomycosis empirically, falsely believing that they can make the diagnosis based on history and clinical inspection alone. We propose and provide evidence for why the diagnosis of onychomycosis should be confirmed by objective methods in each patient before initiating treatment. PMID- 26807604 TI - Long-term symptomatic control of Zenker diverticulum by flexible endoscopic mucomyotomy with the hook knife and predisposing factors for clinical recurrence. AB - OBJECTIVE: Flexible endoscopic treatment for Zenker diverticulum (ZD) is well established. Although recurrence of symptoms is relatively frequent, it has hardly been studied. In the present study, we analyse the long-term development of ZD patients' symptoms after successful endoscopic mucomyotomy, as well as interventional safety, sustainability of success, and predisposing factors for clinical recurrence. METHODS: Forty-six consecutive patients (54% male, mean age 67 years) with symptomatic ZD were treated using a hook knife and soft diverticuloscope. Follow-up interviews at 1 and 6 months inquired about a broad pool of symptoms and the dysphagia score. For further analysis, patients were retrospectively stratified into a 'recurrence' and 'no recurrence' group. RESULTS: After 100% initial success, 30% of patients reported recurrence of symptoms after 4.4 months (range 1-40) and were re-treated (mean 1.39 sessions/patient). Though the 'recurrence' group showed a higher dysphagia score and frequency past intervention, endoscopic re-treatment achieved equally good results as in the 'no recurrence' group. Before treatment, 'recurrence' patients had more severe symptoms, such as vomiting (frequency score 2.13 vs. 0.92; p < 0.05), ZD-related insomnia (1.65 vs. 1.08, n.s.), and a higher dysphagia score (2.25 vs. 1.59, n.s.). Also, the 'recurrence' group had larger diverticula, more men, slightly younger age and a longer duration of symptoms. CONCLUSIONS: Endoscopic treatment of ZD with hook knife and soft diverticuloscope is safe and effective. Despite considerable clinical recurrence, re-treatment achieved a long lasting freedom of symptoms. Male patients with a high dysphagia score and severe symptoms were more likely to experience recurrence. PMID- 26807605 TI - Needle Thoracostomy in the Prehospital Setting: A Retrospective Observational Study. AB - BACKGROUND: The use of needle thoracostomy (NT) is a common prehospital intervention for patients in extremis or cardiac arrest due to trauma; however, controversy surrounds its use. The purpose of this study is to compare outcomes, effectiveness, and complications of NT in an Emergency Medical Services (EMS) system that includes urban, rural, and wilderness environments. METHODS: This is a retrospective observational study of all patients who had NT performed in a four county EMS system with a catchment area of greater than 1.6 million people. All prehospital records where NT was performed were queried for demographics, mechanism of injury, initial status, and clinical change following NT. Hospital records were queried for exam findings on arrival to the hospital, any complications from NT, and final outcome. The Trauma Registry was accessed to obtain Injury Severity Scores. Information was manually abstracted by study investigators and univariate analysis utilizing chi-squared and two-tailed t tests were initially conducted before a multivariate analysis was conducted utilizing a binary logistic regression model. RESULTS: A total of 169 patients with a mean age of 38 years were included in this study; 87% were male and 61% sustained blunt trauma. The overall mortality rate was 79%; 77% in the blunt trauma group; and 83% in the penetrating group, with no significant difference between the two groups relative to mortality (p = 0.336). There was a significant difference in survival between patients who were initially presented as a stat trauma versus as a trauma arrest (52% versus 99%, p > 0.001). The multivariate model with regard to survival supported that reported clinical change after NT (p = 0.001) and status (p = 0.0001) are important indicators of survival. No complications from NT were reported. CONCLUSIONS: NT can safely be performed by paramedics in an EMS system that includes urban, rural, and wilderness settings. Its efficacy does not differ between patients suffering from blunt versus penetrating trauma; however, it appears most beneficial for patients who are unstable but still have vital signs. PMID- 26807606 TI - Potential economic losses to the US corn industry from aflatoxin contamination. AB - Mycotoxins, toxins produced by fungi that colonise food crops, can pose a heavy economic burden to the US corn industry. In terms of economic burden, aflatoxins are the most problematic mycotoxins in US agriculture. Estimates of their market impacts are important in determining the benefits of implementing mitigation strategies within the US corn industry, and the value of strategies to mitigate mycotoxin problems. Additionally, climate change may cause increases in aflatoxin contamination in corn, greatly affecting the economy of the US Midwest and all sectors in the United States and worldwide that rely upon its corn production. We propose two separate models for estimating the potential market loss to the corn industry from aflatoxin contamination, in the case of potential near-future climate scenarios (based on aflatoxin levels in Midwest corn in warm summers in the last decade). One model uses the probability of acceptance based on operating characteristic (OC) curves for aflatoxin sampling and testing, while the other employs partial equilibrium economic analysis, assuming no Type 1 or Type 2 errors, to estimate losses due to proportions of lots above the US Food and Drug Administration (USFDA) aflatoxin action levels. We estimate that aflatoxin contamination could cause losses to the corn industry ranging from US$52.1 million to US$1.68 billion annually in the United States, if climate change causes more regular aflatoxin contamination in the Corn Belt as was experienced in years such as 2012. The wide range represents the natural variability in aflatoxin contamination from year to year in US corn, with higher losses representative of warmer years. PMID- 26807607 TI - Occipital nerve stimulation and beyond: when is invasive peripheral stimulation for headaches appropriate? PMID- 26807608 TI - Molecular Analysis of Sarcoidosis Granulomas Reveals Antimicrobial Targets. AB - Sarcoidosis is a granulomatous disease of unknown cause. Prior molecular and immunologic studies have confirmed the presence of mycobacterial virulence factors, such as catalase peroxidase and superoxide dismutase A, within sarcoidosis granulomas. Molecular analysis of granulomas can identify targets of known antibiotics classes. Currently, major antibiotics are directed against DNA synthesis, protein synthesis, and cell wall formation. We conducted molecular analysis of 40 sarcoidosis diagnostic specimens and compared them with 33 disease control specimens for the presence of mycobacterial genes that encode antibiotic targets. We assessed for genes involved in DNA synthesis (DNA gyrase A [gyrA] and DNA gyrase B), protein synthesis (RNA polymerase subunit beta), cell wall synthesis (embCAB operon and enoyl reductase), and catalase peroxidase. Immunohistochemical analysis was conducted to investigate the locale of mycobacterial genes such as gyrA within 12 sarcoidosis specimens and 12 disease controls. Mycobacterial DNA was detected in 33 of 39 sarcoidosis specimens by quantitative real-time polymerase chain reaction compared with 2 of 30 disease control specimens (P < 0.001, two-tailed Fisher's test). Twenty of 39 were positive for three or more mycobacterial genes, compared with 1 of 30 control specimens (P < 0.001, two-tailed Fisher's test). Immunohistochemistry analysis localized mycobacterial gyrA nucleic acids to sites of granuloma formation in 9 of 12 sarcoidosis specimens compared with 1 of 12 disease controls (P < 0.01). Microbial genes encoding enzymes that can be targeted by currently available antimycobacterial antibiotics are present in sarcoidosis specimens and localize to sites of granulomatous inflammation. Use of antimicrobials directed against target enzymes may be an innovative treatment alternative. PMID- 26807609 TI - The role of pharmacogenetics and advances in gene therapy in the treatment of diabetic retinopathy. AB - Diabetic retinopathy (DR) and its complications such as diabetic macular edema continue to remain a major cause for legal blindness in the developed world. While the introduction of anti-tVEGF agents has significantly improved visual outcomes of patients with DR, unpredictable response, largely due to genetic polymorphisms, appears to be a challenge with this therapy. With advances in identification of various genetic biomarkers, novel therapeutic strategies consisting of gene transfer are being developed and tested for patients with DR. Application of pharmacogenetic principles appears to be a promising futuristic strategy to attenuate diabetes-mediated retinal vasculopathy. In this comprehensive review, data from recent studies in the field of pharmacogenomics for the treatment of DR have been provided. PMID- 26807611 TI - Novel magneto-luminescent effect in LSMO/ZnS:Mn nanocomposites at near-room temperature. AB - We report the tuning of the internal Mn photoluminescence (PL) transition of magnetically-ordered Sr-doped lanthanum manganite (LSMO)/Mn-doped zinc sulfide (ZnS:Mn) nanocomposites (NCs) by applying a static magnetic field in the range of 0-1 T below the critical temperature of ~225 K. To do that, we have systematically fabricated LSMO/ZnS:Mn at different concentrations (1:1, 1:3, 1:5 and 1:10 wt%) via a straightforward solid-state reaction. X-ray diffraction and Raman analyses reveal that both phases coexist with a high degree of crystallinity and purity. Electron microscopy indicates that the NCs are almost spherical with an average crystal size of ~6 nm, and that their surfaces are clean and smooth. The bifunctional character of LSMO/ZnS:Mn was evidenced by vibrating sample magnetometry and PL spectroscopy analyses, which show a marked ferromagnetic behavior and a broad, intense Mn orange emission band at room temperature. Moreover, the LSMO/ZnS:Mn at 1:3 wt% exhibits magneto-luminescent (ML) coupling below 225 K, and reaches the largest suppression of Mn-band PL intensity (up to ~10%) at 150 K, when a magnetic field of 1.0 T is applied. The ML effect persists at magnetic fields as low as 0.2 T at 8 K, which can be explained by evoking a magnetic-ordering-induced spin-dependent restriction of the energy transfer to Mn states. No ML effect was observed in bare ZnS:Mn nanoparticles under the same experimental parameters. Our findings suggest that this NC can be considered as a new ML compound, similar to FeCo/InGaN-GaN and LSMO/ZnO NCs, useful as q-bits for quantum computation. The results presented here bring forth new avenues to better understand the interaction between semiconductors and perovskites, and exploit their synergistic effects in magneto optics, spintronics and nanoelectronics. PMID- 26807610 TI - Complete Genome Characterization of the Arumowot Virus (Unclassified Phlebovirus) Isolated from Turdus libonyanus Birds in the Central African Republic. AB - The Bunyaviridae family is currently composed of five genera, including Phlebovirus, in which several phleboviruses are associated with human diseases. Using high-throughput sequencing, we obtained and characterized one complete genome of the Arumowot virus (AMTV) isolated in 1978 from Turdus libonyanus, the Kurrichane Thrush, in the Central African Republic (CAR). The genomic segment of the new strain of AMTV isolated in the CAR had 75.4-83.5% sequence similarity and 82-98.4% amino acid similarity to the prototype sequence of AMTV. The different conserved proteins of the small (S) and large (L) segments (Nc, NSP, and RNA polymerase) showed close similarity at the amino acid level, whereas the polyprotein of the medium (M) segment was highly divergent, with 18% and 37.7%, respectively, for the prototype sequence of AMTV and the Odrenisrou virus (ODRV) isolated from Culex (Cx.) albiventris mosquitoes in the Tai forest, Ivory Coast. Phylogenetic analysis confirmed the sequence homology analysis and indicated that AMTV-CAR clustered into the Salehabad virus antigenic complex. The two closest viruses were the prototype sequences of AMTV originally isolated from Cx. antennatus mosquitoes and ODRV. These molecular data suggest the need for a deep genetic characterization of the diversity of this viral species to enhance its detection in the Central African region and to understand better its behavior and life cycle so that its potential spread to the human population can be prevented. PMID- 26807612 TI - Muon-spin relaxation study of the double perovskite insulators Sr2 BOsO6 (B = Fe, Y, ln). AB - We present the results of zero-field muon-spin relaxation measurements made on the double perovskite insulators Sr2 BOsO6 (B = Fe,Y, In). Spontaneous muon-spin precession indicative of quasistatic long range magnetic ordering is observed in Sr2FeOsO6 within the AF1 antiferromagnetic phase for temperatures below [Formula: see text] K. Upon cooling below T2~67 K the oscillations cease to be resolvable owing to the coexistence of the AF1 and AF2 phases, which leads to a broader range of internal magnetic fields. Using density functional calculations we identify a candidate muon stopping site within the unit cell, which dipole field simulations show to be consistent with the proposed magnetic structure. The possibility of incommensurate magnetic ordering is discussed for temperatures below TN = 53 K and 25 K for Sr2YOsO6 and Sr2InOsO6, respectively. PMID- 26807613 TI - Aneurysms Encased in Meningiomas: A Case Report and Review of the Literature. AB - The coexistence of aneurysms and meningiomas is rare, and encasement of an aneurysm within a meningioma even more so. We report a case of an optic nerve sheath meningioma encasing an aneurysm of the internal carotid artery and present a brief review of the literature. PMID- 26807614 TI - Navigable 3D-Ultrasound Facilitates Supra-Radical Resections beyond the Contrast Enhancing Boundaries in Malignant Gliomas. PMID- 26807615 TI - Ten-Day Response to CT-Guided Spinal Infiltration Therapy in More Than a Thousand Patients. AB - BACKGROUND AND STUDY AIMS: Infiltration therapy (IT) for degenerative spine disease is considered a valuable nonsurgical treatment option in the absence of severe neurologic deficits. The aim of this study was to evaluate the 10-day response to computed tomography (CT)-guided IT and to identify parameters that are positively or negatively associated with short-term outcome. PATIENTS AND METHODS: We conducted a prospective study on 1327 consecutive patients that received CT-guided IT for various spinal disorders between February 2007 and June 2013. Different steroids (betamethasone, dexamethasone, triamcinolone) with or without bupivacaine were applied using different approaches (direct and indirect for cervical nerve roots; transforaminal and interlaminar as well as combined approaches for lumbar nerve roots; facet joint and sacroiliac joint infiltration). The primary end point was the patients' response 10 days after IT, which was graded as better, the same, or worse. The chi-square test was used for subgroup comparisons. RESULTS: A total of 1002 patients provided 10-day follow up. Clinically meaningful pain relief was achieved in 65 of 107 patients treated for cervical disk herniation (60.8%), 27 of 60 for cervical foraminal stenosis (45%), 295 of 412 for lumbar disk herniation (71.6%), 134 of 199 for lumbar spinal stenosis (LSS) (67.3%), 35 of 61 for cervical facet joint pain (57.4%), 87 of 128 for lumbar facet joint pain (68%), and 25 of 35 for sacroiliac joint syndrome (SIJS) (71.4%). There was no difference with regard to the infiltration technique, types, and doses of steroids administered or the add-on of local anesthetics. An age-dependent difference was shown for elderly patients with LSS and SIJS. Repeated infiltrations were equally effective in alleviating pain compared with the first infiltration. CONCLUSIONS: CT-guided IT for various spinal disorders has an overall positive response rate of 66.7% after 10 days. Outcome was not unduly influenced by technical variations in technique, types, and doses of steroids administered and probably relates better to the correct indication than to technical aspects. PMID- 26807616 TI - Bedside Treatment of Chronic Subdural Hematoma: Using Radiographic Characteristics to Revisit the Twist Drill. AB - BACKGROUND AND STUDY AIMS: Conventional treatment strategies for the management of symptomatic chronic subdural hematoma (cSDH) in the elderly include observation, operative burr holes or craniotomy, and bedside twist drill drainage. The decision on which technique to use should be determined by weighing the comorbidities and symptoms of the patient with the potential risks and benefits. The goal of this study was to identify radiographic characteristics on computed tomography scan that might be used to guide surgical decision making in terms of operative versus bedside removal of cSDH. METHODS: We retrospectively reviewed clinical and radiographic features in patients who underwent bedside twist drill evacuation of a cSDH and those for a cohort of patients who underwent operative intervention via burr holes. RESULTS: We did not identify any clinical features or preoperative imaging characteristics to suggest an advantage of one procedure over the other. Additionally, complete radiographic resolution of cSDH on postoperative imaging is not required to relieve patient symptoms. CONCLUSION: Although bedside twist drill evacuation may avoid operating room costs and anesthetic complications in an elderly patient population and allow earlier resumption of anticoagulation treatment if necessary, there is also a risk of morbidity if uncontrolled bleeding is encountered or the patient is unable to tolerate the bedside procedure. However, bedside twist drill craniostomy is a reasonable and effective option for the treatment of subacute/chronic SDH in patients who may not be optimal surgical candidates. PMID- 26807617 TI - Outcome after In-Hospital Rebleeding of Rupture of Intracranial Aneurysms. AB - BACKGROUND: After initial subarachnoidal hemorrhage (SAH), due to an intracranial aneurysm, rebleeding is known as a factor influencing the devastating outcome. This complication has been reported to occur in ~ 4% of the patients admitted with aneurysmal SAH. Moreover, ultra-early rebleeding within the first 24 hours might occur in 9 to 17% of the cases (40-87% appearing in the first 6 hours). Risk factors influencing this situation include increasing aneurysm size, deterioration of neurologic deficits, angiography within 3 hours of bleeding, sentinel symptoms, and the loss of consciousness at initial bleeding. The aim of this retrospective study was to assess factors and potential risk factors related to rebleeding, specifically the interval from initial SAH to rebleeding. MATERIAL AND METHODS: From a consecutive series of 243 patients who experienced aneurysmal SAH, we identified 28 patients (11.5%; 12 men, 16 women; mean age: 58 +/- 10 years) who developed in-hospital rebleeding during this 49-month study (2009 2013). Demographic, radiologic, and clinical characteristics including hemodynamic parameters were analyzed. RESULTS: Rebleeding was fatal in 20 of the 28 patients (71%) and caused severe neurologic deficits (Glasgow Outcome Scale: 3; modified Rankin Scale: 5) in 3 (29%) of the remaining 8 survivors. Rebleeding occurred within the first 4 hours in 15 patients (54%) within 7, 24, and 48 hours in 17 (61%), 6 (21%), and 1 (4%) patient, respectively. In this series, the medium arterial blood pressure was 98 +/- 11 mm Hg at arrival at the emergency department, 88 +/- 10 mm Hg before rebleeding, and it dramatically increased to 124 +/- 22 mm Hg at rebleeding. For the patients with rebleeding after aneurysmal SAH, initial sentinel headache (79%) and loss of consciousness (68%) were the common presenting symptoms. The World Federation of Neurological Societies grade was documented on admission as follows: 1-3 (n = 14 [50%]); 4-5 (n = 14 [50%]). A Fisher grade 4 was documented in 82% of the cases on the initial computed tomography (CT) scan. Overall, 42% of the cases underwent endovascular (n = 6) or microsurgical occlusion of the aneurysm (n = 6). The rest of the patients (n = 16, 58%) did not underwent occlusion of the aneurysm because of poor clinical status. Digital substraction angiography was performed in 61% of the cases. CONCLUSION: Possible factors increasing the risk of in-hospital rebleeding after aneurysmal SAH are high systolic blood pressure, sentinel headache, initial loss of consciousness, poor Hunt and Hess grade, high Fisher grade on initial CT, large aneurysm size, and the performance of angiography. Most of the rebleedings in patients in our center are likely to occur within 7 hours after admission. Based on our findings, we suggest that mobilization of the patient and maneuvers including invasive procedures should be restricted to a minimum during intensive care unit treatment prior to the occlusion of the ruptured aneurysm. Stabilization of blood pressure with adequate sedation and analgesia prior to occlusion can be considered preventive strategies against rebleeding. PMID- 26807618 TI - Oncologic Outcomes of Invasive Squamous Cell Carcinoma of the Scalp Requiring Resection of Cranial Bone. AB - Objectives To identify the recurrence rates and survival outcomes of patients with invasive squamous cell carcinoma of the scalp. Methods This study was a retrospective chart review of eight patients that had squamous cell carcinoma of the scalp with either periosteal or skull invasion on clinical and/or radiographic evaluation. Results The disease-free survival was 62.5% (5/8 patients) with a local control rate of 75% (6/8 patients) for the entire group. The two patients with full-thickness craniectomy had a local control rate of 100% (2/2 patients); the patients with outer cortex removal had a local control rate of 66.7% (4/6 patients). The disease-free survival of the full-thickness group was 50% (1/2 patients ), and the disease-free survival of the outer cortex removal patients was 66.7% (4/6 patients). Conclusion Despite the invasive nature of this disease, a high degree of local control can be achieved in this high-risk group with multiple comorbidities using outer cortex drilldown, and, in properly selected patients, full-thickness calvarial resection. We conclude that for patients without evidence of medullary involvement that outer table drilldown offers a well-tolerated approach with reasonable oncologic control. PMID- 26807619 TI - Endovascular Management of Spinal Dural Arteriovenous Fistulas. AB - Spinal vascular malformations, although rare, cause devastating disease. These malformations are commonly categorized as follows: spinal arteriovenous malformations (AVMs), dural arteriovenous fistulas (DAVFs), spinal hemangiomas, cavernous angiomas, and aneurysms. Spinal DAVFs (SDAVFs), or type 1 spinal AVMs, occur most frequently, representing ~ 60 to 80% of vascular malformations of the spinal cord. While previously microsurgical treatment was considered the gold standard in the treatment of SDAVFs, recent advancements in technology advancements of magnetic resonance imaging as a screening examination, contrast enhanced magnetic resonance angiography, multidetector computed tomography as preangiographic evaluations, digital subtraction angiography, diagnostic catheters, and embolization materials-have made endovascular treatment a possible option. We review the treatment of SDAVFs, primarily discussing the endovascular management of these lesions. PMID- 26807620 TI - Rectangular Tubular Retractor for Microendoscopic Lumbar Decompression. AB - Background A cylindrical working tube with a diameter of 16 mm has been used for endoscopic posterior lumbar spinal surgery. However, intraoperative muscle resection is significant when using the current conventional tubular retractor. Objective To describe a novel tubular retractor for microendoscopic surgery and to analyze the outcomes of lumbar decompressive laminotomy using this retractor. Materials and Methods We devised a novel tubular retractor by changing the medial and lateral sides of the conventional 16-mm cylindrical tubular retractor to planes with a mediolateral dimension of 10 mm (rectangular tubular retractor hereafter). The amount of muscle resection, osteotomy angle on the approach side, and operating time were compared between 25 intervertebral levels treated by bilateral decompression through a unilateral approach using the rectangular tubular retractor and 31 intervertebral levels treated with the same surgery using a 16-mm cylindrical tubular retractor. Results Due to the short mediolateral dimension, muscle resection decreased by 86%. The rectangular tubular retractor also decreased early postoperative wound pain. Because the craniocaudal dimension of the tubular retractor was maintained, surgical difficulty did not increase, resulting in only a slight increase in operating time. The facet joint on the approach side could be sufficiently preserved. Conclusions The rectangular tubular retractor reduced surgical invasiveness without increasing surgical difficulty. PMID- 26807621 TI - Long-term outcome of intravascular ultrasound application in patients with moderate coronary lesions and grey-zone fractional flow reserve. AB - OBJECTIVE: This study aimed to assess the long-term outcome of intravascular ultrasound (IVUS) application in patients with a fractional flow reserve (FFR) of 0.75-0.80. BACKGROUND: Scientifically evaluating anatomical structures is vital because structure influences both physiological function and decision-making in moderate coronary lesions, especially for those with an FFR of 0.75-0.80. MATERIALS AND METHODS: Patients (n=128) were divided into three groups based on treatment: the drug control group (n=40), the IVUS-percutaneous coronary intervention (PCI) group (n=40) and the IVUS-drug group (n=48). A PCI was performed when a patient had a minimum lumen area less than 4 mm(2) and a plaque burden of 70% or greater. Major adverse clinical events were defined as cardiac death, nonfatal myocardial infarction, target vessel revascularization, including PCI or coronary artery bypass grafting, and unstable angina, all of which were also evaluated during follow-up. RESULTS: Kaplan-Meier curves indicated that the incidence of major adverse clinical events did not differ between the IVUS-PCI and IVUS-drug groups (5 vs. 6.3%, P=0.810), but the levels in both of these groups significantly decreased compared with the drug control group (5 vs. 22.5%, P=0.024, and 6.5 vs. 22.5%, P=0.026, respectively). CONCLUSION: The long-term outcome of the application of IVUS in patients with a grey-zone FFR of 0.75-0.80 was superior to that of patients who were treated only with drugs without IVUS measurement. Patients with a grey-zone FFR should receive an individualized treatment strategy according to their IVUS parameters. Patients with the same FFR values may require different treatment strategies. PMID- 26807622 TI - A recurrent coronary honeycomb-like structure: insights from angioscopy and optical coherence tomography. PMID- 26807623 TI - Evaluation and management of hydronephrosis in the neonate. AB - PURPOSE OF REVIEW: The prenatal detection of congenital anomalies of the kidney and urinary tract (CAKUT) has permitted the early management of these conditions. The aim of this review is to provide an overview of the management of neonates with antenatal hydronephrosis (ANH). RECENT FINDINGS: In spite of the continuous advances in the understanding of the genetic basis, clinical course, and outcomes of CAKUT, there are still many controversies regarding the clinical significance, postnatal evaluation, and management of neonates with ANH. Mild ANH will often resolve spontaneously, whereas moderate to severe ANH is frequently associated with CAKUT. SUMMARY: ANH is a surrogate marker of potential congenital renal anomalies, but usually cannot identify a specific disease. A multidisciplinary team approach is required to diagnose and treat these complex disorders. Currently nonsurgical management of CAKUT should be considered whenever possible for infants with ANH. PMID- 26807624 TI - Cortisol Levels in a Catatonic Patient Treated Daily With Electroconvulsive Therapy Using Etomidate Narcosis. PMID- 26807625 TI - Improving the Medical Assessment of Patients Before Electroconvulsive Therapy: An Audit Across Two Sites. AB - OBJECTIVE: It is essential that a medical assessment is completed before commencing electroconvulsive therapy (ECT) to identify possible risk factors that may complicate anesthesia. This audit aimed to improve the physical examination and documented medical history of this assessment usually performed by referring psychiatrists. METHODS: Patients from 2 sites (A and B) were retrospectively audited against standards from the Scottish ECT Accreditation Network. The timing and systems examined for the physical examination were noted. Site A used an examination sheet; at site B there was no standard way of recording examination. Documented medical histories were compared with comprehensive histories obtained using multiple sources. Discrepancies were noted. Site A was reaudited after amending the examination sheet and adding prompts to use multiple sources when gathering histories. RESULTS: There were repeat examinations for ECT in 30 patients (100%) at site A and 6 (23%) of 26 at site B. Physical examinations were incomplete in 47% of patients at A and 100% at B. Oral examination was frequently missed at both sites. Medical histories were accurate in 20% at A and 38% at B. In the reaudit of site A, all 12 patients had a complete repeat examination; histories were accurate in 8 (67%), with multiple sources used in 11 (92%). CONCLUSIONS: Incomplete or inaccurate assessments put patients at risk. Oral examinations should be part of initial medical assessments. This audit shows the benefits of using a physical examination sheet to ensure a repeat complete examination. Using multiple sources to gather medical histories is encouraged. PMID- 26807626 TI - ANALYSIS OF THREE-DIMENSIONAL CHOROIDAL VOLUME WITH ENHANCED DEPTH IMAGING FINDINGS IN PATIENTS WITH BIRDSHOT RETINOCHOROIDOPATHY. AB - PURPOSE: To describe changes in three-dimensional choroidal volume and thickness with full raster scans of enhanced depth imaging optical coherence tomography in patients with birdshot retinochoroidopathy. METHODS: This prospective case series collected spectral domain optical coherence tomography images with the enhanced depth imaging technique from eight eyes of eight patients with birdshot retinochoroidopathy including four active patients (four eyes) and four quiet patients (four eyes). Fifty scans of each patient were manually segmented before automated built-in calibration software was used. RESULTS: Of all active patients, there were no statistically significant differences in the total choroidal volume and mean central choroidal thickness between the active and inactive phase over 6 months of follow-up. Alterations in choroidal parameters were evident and consistent after amelioration of inflammation, whereas the retinal volume and thickness remained stable. Regarding the eight inactive eyes at 6 months, the mean total choroidal volume and mean central choroidal thickness were significantly less than historical controls (P = 0.03 and P < 0.001, respectively). Persistent suprachoroidal hyporeflective space in two patients was noted despite the fact that clinical inflammation completely subsided at 6 months. CONCLUSION: Choroidal volume and thickness changes were consistent with inflammation in patients with birdshot retinochoroidopathy. Patients with inactive birdshot retinochoroidopathy have significant reduction in choroidal volume and thickness than do normal patients. PMID- 26807627 TI - SMARTPHONE-BASED DILATED FUNDUS PHOTOGRAPHY AND NEAR VISUAL ACUITY TESTING AS INEXPENSIVE SCREENING TOOLS TO DETECT REFERRAL WARRANTED DIABETIC EYE DISEASE. AB - PURPOSE: To compare clinical assessment of diabetic eye disease by standard dilated examination with data gathered using a smartphone-based store-and-forward teleophthalmology platform. METHODS: 100 eyes of 50 adult patients with diabetes from a health care safety-net ophthalmology clinic. All patients underwent comprehensive ophthalmic examination. Concurrently, a smartphone was used to estimate near visual acuity and capture anterior and dilated posterior segment photographs, which underwent masked, standardized review. Quantitative comparison of clinic and smartphone-based data using descriptive, kappa, Bland-Altman, and receiver operating characteristic analyses was performed. RESULTS: Smartphone visual acuity was successfully measured in all eyes. Anterior and posterior segment photography was of sufficient quality to grade in 96 and 98 eyes, respectively. There was good correlation between clinical Snellen and smartphone visual acuity measurements (rho = 0.91). Smartphone-acquired fundus photographs demonstrated 91% sensitivity and 99% specificity to detect moderate nonproliferative and worse diabetic retinopathy, with good agreement between clinic and photograph grades (kappa = 0.91 +/- 0.1, P < 0.001; AUROC = 0.97, 95% confidence interval, 0.93-1). CONCLUSION: The authors report a smartphone-based telemedicine system that demonstrated sensitivity and specificity to detect referral-warranted diabetic eye disease as a proof-of-concept. Additional studies are warranted to evaluate this approach to expanding screening for diabetic retinopathy. PMID- 26807628 TI - A NOVEL P.ASP304GLY MUTATION IN BEST1 GENE ASSOCIATED WITH ATYPICAL BEST VITELLIFORM MACULAR DYSTROPHY PHENOTYPE AND HIGH INTRAFAMILIAL VARIABILITY. AB - PURPOSE: To report the atypical phenotypic characteristics of patients with a novel p.Asp304Gly mutation in BEST1. METHODS: Affected individuals underwent a complete ophthalmic examination, including best-corrected visual acuity, fundus autofluorescence, spectral domain optical coherence tomography, and electrophysiologic testing. All individuals were screened for mutations in the BEST1 gene. RESULTS: Five patients of the same Italian family were clinically examined. All patients complained of decreased vision as the initial symptom. Best-corrected visual acuity ranged from 20/800 to 20/32. On fundus examination, all patients showed atypical Best vitelliform macular dystrophy phenotype with multifocal macular and extramacular involvement. The spectral domain optical coherence tomography characteristics of central macular and extramacular lesions varied in each patient and included "giant" choroidal excavation, extensive flat macular elevation with hyporeflective subretinal material accumulation surrounded by hyperautofluorescent spots/annulus, and extensive hypoautofluorescent extramacular atrophic areas. Electrooculogram was always abnormal with Arden ratio lower than 1.55, whereas electroretinogram was normal in the two younger patients and abnormal (low amplitude) in the three older patients. Genetic analysis revealed a novel missense mutation in BEST1, substituting aspartate for glycine at amino acid 304. CONCLUSION: We describe the atypical phenotype and high intrafamilial variability associated with a new mutation in the BEST1 gene in an Italian family affected with Best vitelliform macular dystrophy. Clinicians should consider screening the BEST1 gene even in the absence of the typical phenotype and in case of high intrafamilial variability. PMID- 26807629 TI - RETINAL VASCULAR PLEXUSES' CHANGES IN DRY AGE-RELATED MACULAR DEGENERATION, EVALUATED BY MEANS OF OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY. AB - PURPOSE: To investigate alteration in superficial and deep retinal vascular densities and choroidal thickness, in patients affected by early and intermediate age-related macular degeneration (AMD). METHODS: All patients had undergone optical coherence tomography angiography (OCTA). All eyes were grouped into two stages: "early AMD" and "intermediate AMD." Outcome measures were superficial vessel density, deep vessel density, and choroidal thickness. A control group of healthy subjects was selected for the statistical comparisons. RESULTS: A total of 37 eyes of 37 dry AMD patients were enrolled for the study. Fourteen of 37 eyes were classified as having early AMD, the remaining 23 of 37 eyes were classified as being affected by intermediate AMD. Superficial and deep vessel densities were 39.21% +/- 10.67% and 43.84% +/- 11.57%, respectively, in the control group and 28.30% +/- 10.73% and 36.41% +/- 12.30%, respectively, in AMD patients (P = 0.001 and P = 0.017, respectively). Choroidal thickness was significantly reduced in AMD patients. CONCLUSION: In the last years, several studies have reported vascular factors playing an important role in AMD pathogenesis. We demonstrated that both superficial and deep retinal plexuses are altered among patients affected by AMD. Interestingly, this alteration starts immediately at the intermediate AMD stage and also the choroidal thickness reduction. PMID- 26807630 TI - SURGICAL MANAGEMENT OF ADVANCED FAMILIAL EXUDATIVE VITREORETINOPATHY WITH COMPLICATIONS. AB - PURPOSE: To report the management of complicated advanced familial exudative vitreoretinopathy in a predominantly young population. METHODS: This retrospective study was performed on 34 eyes of 25 patients with severe complications of advanced familial exudative vitreoretinopathy, including retinal detachment, corneal opacity, shallow or flat anterior chamber, cataract, posterior pupillary adhesion, secondary glaucoma, vitreous hemorrhage, and preretinal hemorrhage. Preoperative and postoperative clinical information was reviewed. RESULTS: The average age of the patients was 3.52 +/- 5.94 years. Of the 34 eyes, 22 underwent lensectomy, 9 underwent lensectomy combined with vitrectomy, 2 underwent staged lensectomy and vitrectomy, and 1 underwent lens sparing vitrectomy. After surgery, the shallow or flat anterior chamber became normal in 26/28 eyes; corneal opacity disappeared or improved in 10/22 eyes; and secondary glaucoma was controlled in 22/24 eyes. Among the 12 eyes operated by vitrectomy, the retina was attached in 5 eyes and partly attached in 7. Final visual acuity ranged from no light perception to 30/200 (n = 17). All 5 eyes with preoperative and postoperative visual acuity records showed improvement. CONCLUSION: Surgical intervention is recommended to resolve complications of advanced familial exudative vitreoretinopathy and to preserve visual function. Staged lensectomy and vitrectomy is an alternative for advanced familial exudative vitreoretinopathy with corneal complications and/or vascularly active fibrovascular proliferation. PMID- 26807631 TI - INTRAVITREAL VERSUS SUBRETINAL ADMINISTRATION OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR COMBINED WITH GAS FOR ACUTE SUBMACULAR HEMORRHAGES DUE TO AGE-RELATED MACULAR DEGENERATION: An Exploratory Prospective Study. AB - PURPOSE: Current management of submacular hemorrhage (SMH) favors vitrectomy and gas with subretinal administration of recombinant tissue plasminogen activator (rtPA) over mere intravitreal rtPA injections and gas. In this study, we aimed to compare the effectiveness of both treatment modalities to displace submacular blood. METHODS: Twenty-four patients with SMH secondary to age-related macular degeneration were included. The SMH had to exist <=14 days at time of surgery and SMH thickness had to be between 250 MUm and 1,250 MUm. Patients were randomized to either intravitreal injections of rtPA, perfluoropropane (C3F8) gas, and bevacizumab (n = 12) or vitrectomy with subretinal rtPA administration, intravitreal C3F8 gas, and bevacizumab (n = 12). The SMH volume change was measured on spectral domain optical coherence tomography postoperatively within a 2.5-mm cylinder centered at the fovea. RESULTS: Median relative volume reduction of subretinal blood at 6 weeks postoperatively was 97% (95% confidence interval: 91-99%) in the intravitreal rtPA group and 100% (95-100%) in the subretinal rtPA group and did not differ significantly between groups (P = 0.56). CONCLUSION: Both treatment modalities effectively displaced SMH in this exploratory clinical trial. To more definitely study the noninferiority of intravitreal rtPA with gas to subretinal rtPA, vitrectomy with gas, a larger clinical trial would be necessary. PMID- 26807632 TI - WIDE-FIELD INFRARED IMAGING: A Descriptive Review of Characteristics of Retinoschisis, Retinal Detachment, and Schisis Detachments. AB - PURPOSE: Retinoschisis and retinal detachments are primarily differentiated based on characteristic examination findings. In diagnostically challenging cases, noncontact wide-field infrared imaging can help diagnosis and visualize the extent/margins of retinoschisis, retinal detachment, or combined schisis detachments by comparing reflectivity patterns. METHODS: This is a retrospective, observational, descriptive case series of 14 eyes of 14 nonconsecutive patients, ranging from 28 to 89 years old (mean 61), diagnosed with retinoschisis, retinal detachment, or schisis detachment from May 5, 2014 to March 4, 2015. Patients with secondary retinoschisis and/or retinal detachment from other causes were not included in the study. Heidelberg Wide-Field Module lens and Heidelberg Spectralis HRA+OCT machine (Heidelberg Engineering, Heidelberg, Germany) were used to obtain noncontact, wide-field infrared images on each study eye. RESULTS: Seven eyes with retinal detachments, four with retinoschises, and three with schisis detachments were imaged using this novel wide-field infrared technique. Retinoschisis appears light and translucent with prominent vasculature, retinal detachments appear dark and opaque, and combined retinoschisis/retinal detachment exhibit mixed reflectivity patterns. CONCLUSION: Wide-field infrared imaging provides a quick, noncontact, noninvasive method to accurately diagnose and to monitor for progression of retinoschisis, retinal detachment, or combined schisis detachments. PMID- 26807633 TI - CORRELATION BETWEEN SUBFOVEAL CHOROIDAL THICKNESS AND FOVEAL THICKNESS IN THALASSEMIC PATIENTS. AB - PURPOSE: To assess the impact of two iron chelation modalities in thalassemic patients on foveal and subfoveal choroidal thickness. METHODS: The study included 60 beta-thalassemia major patients. They included 30 patients on oral deferasirox after a period of subcutaneous deferoxamine (Group 2) and 30 patients on subcutaneous deferoxamine (Group 3). Thirty age- and sex-matched healthy children were included as a control group (Group 1). All participants underwent a complete ophthalmologic evaluation and Spectral Domain Optical Coherence Tomography. RESULTS: Age, gender, intraocular pressure, best-corrected visual acuity, and refraction were not statistically different between the three studied groups. Ferritin level, pretransfusion hemoglobin, serum iron, and duration of thalassemia were not statistically different between the two thalassemic groups. Foveal thickness in Group 1 (225.15 +/- 17.35 MUm) was statistically higher than in Group 2 (210.53 +/- 21.73 MUm) (P < 0.001) and Group 3 (200.15 +/- 7.34 MUm) (P < 0.001). It was statistically higher in Group 2 than in Group 3 (P = 0.001). Subfoveal choroidal thickness in Group 1 (279.70 +/- 32.54 MUm) was statistically higher than in Group 2 (255.80 +/- 19.20 MUm) (P < 0.001) and Group 3 (248.28 +/- 20.43 MUm) (P < 0.001). It was statistically higher in Group 2 than in Group 3 (P < 0.05). CONCLUSION: Thalassemic patients can develop a significant decrease in foveal thickness because of the inevitable use of chelation therapy. Deferoxamine as a chelating agent can affect foveal thickness more than the oral form (deferasirox). PMID- 26807634 TI - A Simple Hydraulic Analog Model of Oxidative Phosphorylation. AB - Mitochondrial oxidative phosphorylation is the primary source of cellular energy transduction in mammals. This energy conversion involves dozens of enzymatic reactions, energetic intermediates, and the dynamic interactions among them. With the goal of providing greater insight into the complex thermodynamics and kinetics ("thermokinetics") of mitochondrial energy transduction, a simple hydraulic analog model of oxidative phosphorylation is presented. In the hydraulic model, water tanks represent the forward and back "pressures" exerted by thermodynamic driving forces: the matrix redox potential (DeltaGredox), the electrochemical potential for protons across the mitochondrial inner membrane (DeltaGH), and the free energy of adenosine 5'-triphosphate (ATP) (DeltaGATP). Net water flow proceeds from tanks with higher water pressure to tanks with lower pressure through "enzyme pipes" whose diameters represent the conductances (effective activities) of the proteins that catalyze the energy transfer. These enzyme pipes include the reactions of dehydrogenase enzymes, the electron transport chain (ETC), and the combined action of ATP synthase plus the ATP adenosine 5'-diphosphate exchanger that spans the inner membrane. In addition, reactive oxygen species production is included in the model as a leak that is driven out of the ETC pipe by high pressure (high DeltaGredox) and a proton leak dependent on the DeltaGH for both its driving force and the conductance of the leak pathway. Model water pressures and flows are shown to simulate thermodynamic forces and metabolic fluxes that have been experimentally observed in mammalian skeletal muscle in response to acute exercise, chronic endurance training, and reduced substrate availability, as well as account for the thermokinetic behavior of mitochondria from fast- and slow-twitch skeletal muscle and the metabolic capacitance of the creatine kinase reaction. PMID- 26807635 TI - Older Women with Controlled Isolated Systolic Hypertension: Exercise and Blood Pressure. AB - INTRODUCTION: Exercise is generally regarded as beneficial for health, but the consequent increases in blood pressure might pose a risk for hypertensive subjects. The purpose of this study was to determine blood pressure responses to dynamic exercise and sustained handgrip in patients with isolated systolic hypertension (ISH) who were stable on medication. METHODS: Nineteen female ISH patients (66 +/- 5 yr) and 19 age-matched normotensive (NT) female controls undertook a 5-min cycle exercise (60% heart rate reserve [HRR]) and a 2-min handgrip exercise (30% maximum voluntary contraction). Blood pressure responses were measured using an oscillometric cuff, together with heart rate and resting brachial pulse transit times. RESULTS: Systolic blood pressure (SBP) levels after cycle exercise were 194 +/- 18 and 153 +/- 19 mm Hg for ISH and NT, respectively, with the increase above resting being greater for ISH (P < 0.001), and only small changes were found in diastolic blood pressure (DBP). During handgrip exercise, SBP rose to 168 +/- 19 and 140 +/- 8 mm Hg for ISH and NT, respectively. The increases above baseline were greater for ISH both during the exercise and postexercise circulatory occlusion (P = 0.017). The increase in DBP levels during exercise and postexercise occlusion were similar in ISH and NT, suggesting little difference in metaboreflex sensitivity. Pulse transit time was shorter for ISH compared with NT (166 +/- 6 ms and 242 +/- 24 ms, respectively, P < 0.001), indicating stiffer arteries, which would increase SBP but not DBP. CONCLUSION: Despite being well controlled and normotensive control subjects at rest, ISH patients had high SBP responses to both dynamic and static exercises, which may constitute a risk for cardiovascular incidents. PMID- 26807636 TI - High Incidence of Erysipelas After Surgical Treatment for Vulvar Carcinoma: An Observational Study. AB - OBJECTIVES: Vulvar carcinoma is mainly treated surgically and has an overall good prognosis. Despite the development of minimally invasive surgical procedures in recent years, morbidity remains significant. The aim of the study was to determine the incidence and risk factors of erysipelas after surgical treatment for vulvar carcinoma. METHODS: This retrospective observational study was performed within the Comprehensive Cancer Centre South. The study included patients (N = 116) who underwent surgery for primary vulvar carcinoma between 2005 and 2012. Patients with International Federation of Gynecology and Obstetrics stage IA and IV were excluded. Clinical and histopathological data were analyzed using logistic regression, chi(2) tests, Fisher exact tests, independent t tests, and nonparametric tests. Primary outcome was the incidence of postoperative erysipelas and determination of risk factors for erysipelas. Secondary outcome included other comorbidities. RESULTS: A total of 23 patients (20%) with vulvar carcinoma had 1 or more episodes of erysipelas. The risk of developing erysipelas was significantly higher in patients who underwent lymph node dissection than in those who underwent sentinel node biopsy (36% [n = 12] and 14% [n = 11], respectively, P = 0.008) and in patients with lymphedema than in those without (30% [n = 7] and 12% [n = 11], respectively, P = 0.048). Patients with diabetes tended to have a higher incidence of erysipelas than those without (28% vs 18%, P = 0.27). CONCLUSIONS: Erysipelas occurs frequently in patients who undergo surgical treatment for vulvar carcinoma. The risk of erysipelas is 3 times higher in patients who undergo lymph node dissection and in those with lymphedema than in those without, and it tends to be high in patients with diabetes. PMID- 26807637 TI - Cavitron Ultrasonic Surgical Aspirator in Laparoscopic Nerve-Sparing Radical Hysterectomy: A Pilot Study. AB - OBJECTIVE: Pelvic autonomic nerve preservation during radical hysterectomy for cervical cancer has become a priority in recent years. This pilot study was undertaken to evaluate laparoscopic nerve-sparing radical hysterectomy (L-NSRH) using the Cavitron Ultrasonic Surgical Aspirator (CUSA) in women with cervical cancer. METHODS: Patients with stage IB1 or IIA1 cervical cancer underwent L-NSRH with pelvic lymphadenectomy. The patients were randomly assigned to receive L NSRH using a CUSA (CUSA group; n = 24) or using other techniques (non-CUSA group; n = 21). Recovery of bladder function (indwelling catheter time and time to spontaneous voiding) blood loss, duration of hospital stay, lymph node harvesting, and postoperative complications were compared between the 2 groups. Patients were followed for up to 3 years to determine the maintenance of effect. RESULTS: All patients underwent L-NSRH successfully. Intraoperative blood loss was significantly less in the CUSA than in the non-CUSA group (P = 0.005). Length of hospital stay (P = 0.006) and indwelling catheter time (P = 0.008) were both significantly reduced in the CUSA group compared with that in the non-CUSA group. The spontaneous voiding rate 10 days postoperatively was 95.8% with CUSA and 85.7% with non-CUSA techniques. Two patients developed postoperative complications in the CUSA group as did 3 patients in the non-CUSA group. These were cases of lymphocyst formation or urinary tract infection. CONCLUSIONS: Laparoscopic nerve-sparing radical hysterectomy using CUSA was safe and feasible in patients with cervical cancer. Our results provide initial evidence that L NSRH using CUSA preserves pelvic autonomic nerve function. PMID- 26807638 TI - Recurrence of Early Stage Cervical Cancer After Laparoscopic Versus Open Radical Surgery. AB - OBJECTIVE: The aim of the study was to compare site and time to recurrence in patients affected by early stage cervical cancer (CC) treated with laparoscopy radical hysterectomy (LRH) versus abdominal radical hysterectomy (ARH). METHODS: This retrospective study was conducted in a university teaching, tertiary referral center hospital. We included patients undergoing either LRH or open ARH to treat CC. RESULTS: One hundred fifty patients were included, 82 submitted to LRH and 68 submitted to ARH. Baseline characteristics of the 2 groups were comparable, except for body mass index higher in ARH group. Patients undergoing LRH experienced less blood loss (100 vs 400 mL, P < 0.0001), less lymph nodes removed (20 vs 31, P = 0.001), and shorter recovery (4 vs 8 days, P = 0.0005) in comparison with the ARH group. No significant differences were found regarding recurrence rate (9 vs 13, P = 0.17) and time to recurrence (8 vs 17 months, P = 0.066) between LRH and ARH group.Sites of recurrence were also comparable between the 2 groups: 2/9 versus 2/13 (P = 1) local recurrence, 4/9 versus 8/13 (P = 0.66) pelvic recurrence, 4/9 versus 7/13 (P = 1) distant recurrence in LRH and ARH groups, respectively. The most frequent sites of recurrence were pelvic and distant (44.4%) in LRH group and pelvic (61.5%) in ARH group. CONCLUSIONS: Our data demonstrate that early stage CC can be treated with LRH with similar recurrence rates and patterns in comparison with ARH, reassuring its continuing clinical use. PMID- 26807639 TI - Quality of Life in Women After Pelvic Exenteration for Gynecological Malignancies: A Multicentric Study. AB - OBJECTIVES: This retrospective, multicentric study investigates quality-of-life issues and emotional distress in gynecological cancer survivors submitted to pelvic exenteration (PE). METHODS: The Global Health Status scale of European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30; the EORTC QLQ-CX24 (CX24), and EORTC QLQ-OV28 questionnaires were administered at least 12 months from surgery only in women with no evidence of further recurrence after PE. Statistical analysis was performed by the analysis of variance (for repeated measures. RESULTS: Ninety-six subjects affected by gynecological malignancies receiving PE were enrolled in the study. Anterior PE was performed in 47 patients (49%), posterior PE was performed in 29 cases (30.2%), and total PE performed in 20 women (20.8%). In 38 cases (39.6%), a definitive colostomy was performed. Urinary diversion with continent pouch was created in 11 patients. (11.5%), whereas in the remaining cases, a noncontinent pouch was reconstructed. Patients showed a significant discomfort in attitude to disease (71.5 +/- 4.7), body image (48.9 +/- 6.4), financial difficulties (56.2 +/- 5.8), gastrointestinal symptoms (constipation, 47.8 +/- 5.1; diarrhea, 62.4 +/- 6.6; appetite loss, 43.6 +/- 6.7), insomnia (64.5 +/- 6.6), Global Health Status (64.6 +/- 3.8), physical functioning (65.8 +/- 4.6), role functioning (58.8 +/- 5.8), and emotional functioning (67.4 +/- 4.2). A higher number of ostomies (hazard rate [HR], 7.613; P = 0.012), the creation of a noncontinent bladder (HR, 8.230; P = 0.009), and of definitive colostomy (HR, 8.516; P = 0.008) emerged as independent predictors of poorer Global Health Status scores. Older age (HR, 11.235; P = 0.003), vaginal/vulvar cancer (HR, 7.369; P = 0.013), total/posterior PE (HR, 7.393; P = 0.013), higher number of ostomies (HR, 7.613; P = 0.012), the creation of a noncontinent bladder (HR, 8.230; P = 0.009), and of definitive colostomy (HR, 8.516; P = 0.008) emerged as independent predictors of lower body image levels. CONCLUSIONS: Long-term psycho oncological support is strongly recommended. The reduction of ostomies seems the most effective way to improve patients' quality of life. PMID- 26807640 TI - The Efficacy of Low-Dose Paclitaxel Added to Combination Chemotherapy of Carboplatin and Gemcitabine or Pegylated Liposomal Doxorubicin. AB - OBJECTIVE: Paclitaxel is known to produce the "platelet-sparing effect" that prevents the carboplatin-induced decrease in platelet count. We conducted a pilot study to assess whether the addition of low-dose paclitaxel to carboplatin-based combination chemotherapy prevents thrombocytopenia. METHODS: Patients with platinum-sensitive recurrent ovarian cancer received intravenous (IV) paclitaxel at 60 mg/m(2) followed by IV carboplatin at an area under the curve of 6 and IV pegylated liposomal doxorubicin at 30 mg/m(2) on day 1 in a 28-day cycle (DC-LOP) or IV gemcitabine at 1000 mg/m(2) on days 1 and 8 in a 21-day cycle (GC-LOP). RESULTS: During May 2011 to December 2011, 7 patients received 29 cycles of DC LOP; during January 2012 to May 2013, 15 patients received 88 cycles of GC-LOP. Grade 3/4 thrombocytopenia occurred in 2 (33%) of 6 and 9 (56%) of 16 patients in the DC-LOP and GC-LOP groups, respectively. No grade 3/4 nonhematological toxicity was observed. Only one patient who received GC-LOP had grade 2 sensory and motor peripheral neuropathy. Paclitaxel-related toxicities, including muscle pain, arthralgia, and peripheral neuropathy, were consistently rare and mild. The response rates of DC-LOP and GC-LOP were 33% (0, complete response; 2, partial response; 3, stable disease; 1, progression disease) and 50% (2, complete response; 6, partial response; 7, stable disease; 1, progression disease), respectively. CONCLUSIONS: Although low-dose paclitaxel addition did not alleviate thrombocytopenia in the setting of this pilot study, the results do not deny the existence of the "platelet-sparing effect" by low-dose paclitaxel. Further investigation of the carboplatin-based combination chemotherapy including a drug with mild hematological toxicity is warranted. PMID- 26807641 TI - Gemcitabine and Docetaxel Compared With Observation, Radiation, or Other Chemotherapy Regimens as Adjuvant Treatment for Stage I-to-IV Uterine Leiomyosarcoma. AB - OBJECTIVES: We aimed to compare progression-free survival (PFS) and overall survival (OS) among patients with stage I-to-IV uterine leiomyosarcoma (uLMS) who received adjuvant gemcitabine-docetaxel, were observed, received radiation only, or were treated with a chemotherapy regimen other than gemcitabine-docetaxel. METHODS/MATERIALS: This is a retrospective cohort study of 128 women with uLMS. Data included age, body mass index, race, stage, mitotic count, residual disease, adjuvant treatment, PFS, and OS. Variables were compared by Fisher exact or Wilcoxon rank-sum tests. Time to progression or death was plotted using Kaplan Meier curves. Cox proportional hazards regression was used to estimate hazard ratios for progression or death by patient and tumor characteristics. RESULTS: Fifty-six (44%) women received adjuvant chemotherapy, 41 (32%) received adjuvant radiation, and 31 (24%) were observed. Of those receiving chemotherapy, 30 received gemcitabine-docetaxel, and 26 received other chemotherapy. Disease stage for the chemotherapy groups was evenly distributed. In the radiation group, 80% of patients had early-stage disease. Age, body mass index, and residual disease were similar between the groups. Mitotic count was uniformly 10 or greater only in the gemcitabine-docetaxel group. Age, stage, and residual disease were associated with worst PFS and OS. After adjusting for these variables, there was no difference in PFS or OS between gemcitabine-docetaxel and the other treatment groups. CONCLUSIONS: There was no difference in PFS or OS in women with uLMS treated with adjuvant gemcitabine-docetaxel versus those who were observed or received radiation only or a chemotherapy regimen other than gemcitabine docetaxel. There is a need to identify novel therapies to treat this aggressive disease. PMID- 26807642 TI - Clinical Characteristics and Prognosis of Unexpected Uterine Sarcoma After Hysterectomy for Presumed Myoma With and Without Transvaginal Scalpel Morcellation. AB - OBJECTIVE: To identify the prevalence of unexpected uterine sarcoma after total laparoscopic or abdominal hysterectomy for presumed leiomyoma and compare clinical consequences after hysterectomy with and without transvaginal scalpel morcellation (TVSM). METHODS: In this retrospective study, the medical records of patients who had unexpected uterine sarcoma after total laparoscopic or abdominal hysterectomy for presumed leiomyoma between 2009 and 2013 were reviewed. RESULTS: Among 3021 patients who underwent total hysterectomy for presumed leiomyoma, 18 (1/168, 0.60%) had unexpected uterine sarcoma (5 [1/604, 0.17%] had leiomyosarcoma and 13 [1/232, 0.43%] had low-grade endometrial stromal sarcoma). The risk of unexpected leiomyosarcoma increased steadily in ages from the 40s to the 50s, whereas the risk of unexpected endometrial stromal sarcoma (ESS) decreased steadily in the same period. The unexpected sarcoma was identified in 7 (1/158, 0.63%) of 1104 patients treated by laparoscopy and 11 (1/174, 0.57%) of 1917 patients by laparotomy. Transvaginal scalpel morcellation was performed to extract the uterus in majority (78.53%) of the patients with total laparoscopic hysterectomy. Sixteen (88.89%) cases were low grade, and 2 (11.11%) were high grade: 17 at stage I and 1 at stage II. Nine patients underwent a secondary operation, and 11 patients received adjuvant therapy postoperatively. Except for 1 patient with additional power morcellation, all patients with unexpected ESS survived without recurrence after total hysterectomy with and without TVSM, with mean follow-ups of 25.20 (16-36) months and 32.57 (21-50) months, respectively. CONCLUSIONS: The overall incidence of unexpected uterine sarcoma after total hysterectomy for presumed leiomyoma was low. Low-grade endometrial stromal sarcoma was the dominant subtype of unexpected uterine sarcoma in the present study. Currently, incidental TVSM of unexpected ESS during total laparoscopic hysterectomy seemed to cause no additional increase in sarcoma dissemination in the short-term. PMID- 26807643 TI - Outcomes of Incidental Fallopian Tube High-Grade Serous Carcinoma and Serous Tubal Intraepithelial Carcinoma in Women at Low Risk of Hereditary Breast and Ovarian Cancer. AB - OBJECTIVES: The natural history and optimal management of serous tubal intraepithelial carcinoma (STIC), regardless of BRCA status, is unknown. We report the follow-up findings of a series of incidental fallopian tube high-grade serous carcinomas (HGSCs) and STICs identified in women at low risk for hereditary breast and ovarian cancer (HBOC), undergoing surgery for other indications. MATERIALS AND METHODS: Cases of incidental STIC and HGSC were identified from 2008. Patients with known BRCA1 or BRCA2 mutations, or a family history of ovarian or breast cancer before the diagnosis of STIC or HGSC were excluded. A retrospective chart review was conducted to obtain clinical data. RESULTS: Eighteen cases were identified with a median follow-up of 25 months (range, 4-88 months). Twelve of 18 patients had a diagnosis of STIC with no associated invasive HGSC and 6 had STIC associated with other invasive malignancies. Completion staging surgery was performed on 7 of the 18 patients, including 5 of 12 in which there was STIC only identified on primary surgery; 3 cases were upstaged from STIC only to HGSC based on the staging surgery. Recurrence of HGSC occurred in 2 of the 18 patients. BRCA testing was performed on 3 patients, 1 of whom tested positive for a pathogenic BRCA1 mutation. CONCLUSIONS: Our study suggests that completion staging surgery for incidental STICs in non-BRCA patients may be considered. These patients should be offered hereditary testing. The Pelvic-Ovarian cancer INTerception (POINT) Project is an international registry set up to add to our understanding of STICs. PMID- 26807644 TI - Lipid metabolic reprogramming in cancer cells. AB - Many human diseases, including metabolic, immune and central nervous system disorders, as well as cancer, are the consequence of an alteration in lipid metabolic enzymes and their pathways. This illustrates the fundamental role played by lipids in maintaining membrane homeostasis and normal function in healthy cells. We reviewed the major lipid dysfunctions occurring during tumor development, as determined using systems biology approaches. In it, we provide detailed insight into the essential roles exerted by specific lipids in mediating intracellular oncogenic signaling, endoplasmic reticulum stress and bidirectional crosstalk between cells of the tumor microenvironment and cancer cells. Finally, we summarize the advances in ongoing research aimed at exploiting the dependency of cancer cells on lipids to abolish tumor progression. PMID- 26807645 TI - Hypoxia and metabolic adaptation of cancer cells. AB - Low oxygen tension (hypoxia) is a pervasive physiological and pathophysiological stimulus that metazoan organisms have contended with since they evolved from their single-celled ancestors. The effect of hypoxia on a tissue can be either positive or negative, depending on the severity, duration and context. Over the long-term, hypoxia is not usually consistent with normal function and so multicellular organisms have had to evolve both systemic and cellular responses to hypoxia. Our reliance on oxygen for efficient adenosine triphosphate (ATP) generation has meant that the cellular metabolic network is particularly sensitive to alterations in oxygen tension. Metabolic changes in response to hypoxia are elicited through both direct mechanisms, such as the reduction in ATP generation by oxidative phosphorylation or inhibition of fatty-acid desaturation, and indirect mechanisms including changes in isozyme expression through hypoxia responsive transcription factor activity. Significant regions of cancers often grow in hypoxic conditions owing to the lack of a functional vasculature. As hypoxic tumour areas contain some of the most malignant cells, it is important that we understand the role metabolism has in keeping these cells alive. This review will outline our current understanding of many of the hypoxia-induced changes in cancer cell metabolism, how they are affected by other genetic defects often present in cancers, and how these metabolic alterations support the malignant hypoxic phenotype. PMID- 26807647 TI - Effects of Light and Electron Beam Irradiation on Halide Perovskites and Their Solar Cells. AB - Hybrid alkylammonium lead halide perovskite solar cells have, in a very few years of research, exceeded a light-to-electricity conversion efficiency of 20%, not far behind crystalline silicon cells. These perovskites do not contain any rare element, the amount of toxic lead used is very small, and the cells can be made with a low energy input. They therefore already conform to two of the three requirements for viable, commercial solar cells-efficient and cheap. The potential deal-breaker is their long-term stability. While reasonable short-term (hours) and even medium term (months) stability has been demonstrated, there is concern whether they will be stable for the two decades or more expected from commercial cells in view of the intrinsically unstable nature of these materials. In particular, they have a tendency to be sensitive to various types of irradiation, including sunlight, under certain conditions. This Account focuses on the effect of irradiation on the hybrid (and to a small degree, all-inorganic) lead halide perovskites and their solar cells. It is split up into two main sections. First, we look at the effect of electron beams on the materials. This is important, since such beams are used for characterization of both the perovskites themselves and cells made from them (electron microscopy for morphological and compositional characterization; electron beam-induced current to study cell operation mechanism; cathodoluminescence for charge carrier recombination studies). Since the perovskites are sensitive to electron beam irradiation, it is important to minimize beam damage to draw valid conclusions from such measurements. The second section treats the effect of visible and solar UV irradiation on the perovskites and their cells. As we show, there are many such effects. However, those affecting the perovskite directly need not necessarily always be detrimental to the cells, while those affecting the solar cells, which are composed of several other phases as well as the perovskite light absorber, are not always due to the perovskite itself. While we cannot yet say whether perovskite solar cells will or will not be stable over the long-term, the information in this Account should be a useful source to help achieve this goal. PMID- 26807646 TI - EXD2 promotes homologous recombination by facilitating DNA end resection. AB - Repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is critical for survival and genome stability of individual cells and organisms, but also contributes to the genetic diversity of species. A vital step in HR is MRN CtIP-dependent end resection, which generates the 3' single-stranded DNA overhangs required for the subsequent strand exchange reaction. Here, we identify EXD2 (also known as EXDL2) as an exonuclease essential for DSB resection and efficient HR. EXD2 is recruited to chromatin in a damage-dependent manner and confers resistance to DSB-inducing agents. EXD2 functionally interacts with the MRN complex to accelerate resection through its 3'-5' exonuclease activity, which efficiently processes double-stranded DNA substrates containing nicks. Finally, we establish that EXD2 stimulates both short- and long-range DSB resection, and thus, together with MRE11, is required for efficient HR. This establishes a key role for EXD2 in controlling the initial steps of chromosomal break repair. PMID- 26807648 TI - Role of Molecular Dynamics and Related Methods in Drug Discovery. AB - Molecular dynamics (MD) and related methods are close to becoming routine computational tools for drug discovery. Their main advantage is in explicitly treating structural flexibility and entropic effects. This allows a more accurate estimate of the thermodynamics and kinetics associated with drug-target recognition and binding, as better algorithms and hardware architectures increase their use. Here, we review the theoretical background of MD and enhanced sampling methods, focusing on free-energy perturbation, metadynamics, steered MD, and other methods most consistently used to study drug-target binding. We discuss unbiased MD simulations that nowadays allow the observation of unsupervised ligand-target binding, assessing how these approaches help optimizing target affinity and drug residence time toward improved drug efficacy. Further issues discussed include allosteric modulation and the role of water molecules in ligand binding and optimization. We conclude by calling for more prospective studies to attest to these methods' utility in discovering novel drug candidates. PMID- 26807649 TI - Production of renewable fuels by the photohydrogenation of CO2: effect of the Cu species loaded onto TiO2 photocatalysts. AB - The efficient gas phase photocatalytic hydrogenation of CO2 into a desirable renewable fuel was achieved using a Cu-loaded TiO2 photocatalyst system. Enhancing the amount of Ti(3+) relative to Ti(4+) in a Cu-loaded TiO2 photocatalyst provided an excellent opportunity to promote the photohydrogenation of CO2. The coexistence of Cu and Cu(+) species during the photoreaction was shown to efficiently enhance the photocatalytic activity by prolonging the lifetime of the electrons. To achieve the best photoactivity, the Cu species must be maintained at an appropriately low concentration (<=1 wt%). The highest CH4 yield obtained was 28.72 MUmol g(-1). This approach opens a feasible route not only to store hydrogen by converting it into a desirable renewable fuel, but also to reduce the amount of the greenhouse gas CO2 in the atmosphere. PMID- 26807650 TI - Palladium-Catalyzed Sequential Acylation/Cyanation of Aryl Iodides: A Regiospecific Synthesis of 2-Cyanoaryl Ketones. AB - A palladium-catalyzed, norbornene-mediated acylation/cyanation reaction of iodobenzene was developed by the use of acyl chlorides as acylation reagents and cuprous cyanide. The reaction gave the 2-cyanoaryl ketones efficiently by using readily available starting materials. PMID- 26807651 TI - Structure of Particle Networks in Capillary Suspensions with Wetting and Nonwetting Fluids. AB - The mechanical properties of a suspension can be dramatically altered by adding a small amount of a secondary fluid that is immiscible with the bulk phase. The substantial changes in the strength of these capillary suspensions arise due to the capillary force inducing a percolating particle network. Spatial information on the structure of the particle networks is obtained using confocal microscopy. It is possible, for the first time, to visualize the different types of percolating structures of capillary suspensions in situ. These capillary networks are unique from other types of particulate networks due to the nature of the capillary attraction. We investigate the influence of the three-phase contact angle on the structure of an oil-based capillary suspension with silica microspheres. Contact angles smaller than 90 degrees lead to pendular networks of particles connected with single capillary bridges or clusters comparable to the funicular state in wet granular matter, whereas a different clustered structure, the capillary state, forms for angles larger than 90 degrees . Particle pair distribution functions are obtained by image analysis, which demonstrate differences in the network microstructures. When porous particles are used, the pendular conformation also appears for apparent contact angles larger than 90 degrees . The complex shear modulus can be correlated to these microstructural changes. When the percolating structure is formed, the complex shear modulus increases by nearly three decades. Pendular bridges lead to stronger networks than the capillary state network conformations, but the capillary state clusters are nevertheless much stronger than pure suspensions without the added liquid. PMID- 26807652 TI - Cross-Species Analysis of Protein Dynamics Associated with Hydride and Proton Transfer in the Catalytic Cycle of the Light-Driven Enzyme Protochlorophyllide Oxidoreductase. AB - Experimental interrogation of the relationship between protein dynamics and enzyme catalysis is challenging. Light-activated protochlorophyllide oxidoreductase (POR) is an excellent model for investigating this relationship because photoinitiation of the reaction cycle enables coordinated turnover in a "dark-assembled" ternary enzyme-substrate complex. The catalytic cycle involves sequential hydride and proton transfers (from NADPH and an active site tyrosine residue, respectively) to the substrate protochlorophyllide. Studies with a limited cross-species subset of POR enzymes (n = 4) have suggested that protein dynamics associated with hydride and proton transfer are distinct [Heyes, D. J., Levy, C., Sakuma, M., Robertson, D. L., and Scrutton, N. S. (2011) J. Biol. Chem. 286, 11849-11854]. Here, we use steady-state assays and single-turnover laser flash spectroscopy to analyze hydride and proton transfer dynamics in an extended series of POR enzymes taken from many species, including cyanobacteria, algae, embryophytes, and angiosperms. Hydride/proton transfer in all eukaryotic PORs is faster compared to prokaryotic PORs, suggesting active site architecture has been optimized in eukaryotic PORs following endosymbiosis. Visible pump-probe spectroscopy was also used to demonstrate a common photoexcitation mechanism for representative POR enzymes from different branches of the phylogenetic tree. Dynamics associated with hydride transfer are localized to the active site of all POR enzymes and are conserved. However, dynamics associated with proton transfer are variable. Protein dynamics associated with proton transfer are also coupled to solvent dynamics in cyanobacterial PORs, and these networks are likely required to optimize (shorten) the donor-acceptor distance for proton transfer. These extended networks are absent in algal and plant PORs. Our analysis suggests that extended networks of dynamics are disfavored, possibly through natural selection. Implications for the evolution of POR and more generally for other enzyme catalysts are discussed. PMID- 26807653 TI - Materials Properties and Solvated Electron Dynamics of Isolated Nanoparticles and Nanodroplets Probed with Ultrafast Extreme Ultraviolet Beams. AB - We present ultrafast photoemission measurements of isolated nanoparticles in vacuum using extreme ultraviolet (EUV) light produced through high harmonic generation. Surface-selective static EUV photoemission measurements were performed on nanoparticles with a wide array of compositions, ranging from ionic crystals to nanodroplets of organic material. We find that the total photoelectron yield varies greatly with nanoparticle composition and provides insight into material properties such as the electron mean free path and effective mass. Additionally, we conduct time-resolved photoelectron yield measurements of isolated oleylamine nanodroplets, observing that EUV photons can create solvated electrons in liquid nanodroplets. Using photoemission from a time delayed 790 nm pulse, we observe that a solvated electron is produced in an excited state and subsequently relaxes to its ground state with a lifetime of 151 +/- 31 fs. This work demonstrates that femotosecond EUV photoemission is a versatile surface-sensitive probe of the properties and ultrafast dynamics of isolated nanoparticles. PMID- 26807654 TI - ZIF-8 Cooperating in TiN/Ti/Si Nanorods as Efficient Anodes in Micro-Lithium-Ion Batteries. AB - Zeolite imidazolate framework-8 (ZIF-8) nanoparticles embedded in TiN/Ti/Si nanorod (NR) arrays without pyrolysis have shown increased energy storage capacity as anodes for lithium ion batteries (LIBs). A high capacity of 1650 MUAh cm(-2) has been achieved in this ZIF-8 composited multilayered electrode, which is ~100 times higher than the plain electrodes made of only silicon NR. According to the electrochemical impedance spectroscopy (EIS) and (1)H nuclear magnetic resonance (NMR) characterizations, the improved diffusion of lithium ions in ZIF 8 and boosted electron/Li(+) transfer by the ZIF-8/TiN/Ti multilayer coating are proposed to be responsible for the enhanced energy storage ability. The first principles calculations further indicate the favorable accessibility of lithium with appropriate size to diffuse in the open pores of ZIF-8. This work broadens the application of ZIF-8 to silicon-based LIBs electrodes without the pyrolysis and provides design guidelines for other metal-organic frameworks/Si composite electrodes. PMID- 26807655 TI - Influence of Alcohols on the Lateral Diffusion in Phospholipid Membranes. AB - The effects of hexanol and octanol on the lateral mobility of 1,2-dimyristoyl-sn glycero-3-phosphatidylcholine (DMPC) bilayer are investigated by means of pulsed gradient stimulated-echo NMR spectroscopy. Three distinct diffusions are identified for the DMPC/alcohol systems. They are ascribed to the water, the alcohol, and the lipid. We find that the presence of alcohols promotes the lipid diffusion process both in the liquid and in the interdigitated phases. Furthermore, using the Arrhenius approach, the activation energies are calculated. An explanation in terms of a free volume model, that takes into account also the observed increase of the activation energy in both phases, is proposed. The results obtained here are compared with those presented in our previous work on 1,2-palmitoyl-sn-glycero-3-phosphocholine (DPPC) in order to examine the dependence of the lipid translational diffusion process upon the membrane acyl chain length. A peculiar influence of alcohols on different membranes is found. PMID- 26807656 TI - Combined effects of mineral trioxide aggregate and human placental extract on rat pulp tissue and growth, differentiation and angiogenesis in human dental pulp cells. AB - OBJECTIVE: The aim of this study was to evaluate the combined effects of mineral trioxide aggregate (MTA) and human placental extract (HPE) on cell growth, differentiation and in vitro angiogenesis of human dental pulp cells (HDPCs) and to identify underlying signal transduction mechanisms. In vivo dental pulp responses in rats for a pulp-capping agent were examined. MATERIALS AND METHODS: MTS assay. ALP activity test, alizarin red S staining and RT-PCR for marker genes were carried out to evaluate cell growth and differentiation. HUVEC migration, mRNA expression and capillary tube formation were measured to evaluate angiogenesis. Signal transduction was analysed using Western blotting and confocal microscopy. The pulps of rat maxillary first molars were exposed and capped with either MTA or MTA plus HPE. Histologic observation and scoring were performed. RESULTS: Compared to treatment of HDPCs with either HPE or MTA alone, the combination of HPE and MTA increased cell growth, ALP activity, mineralized nodules and expression of marker mRNAs. Combination HPE and MTA increased migration, capillary tube formation and angiogenic gene expression compared with MTA alone. Activation of Akt, mammalian target of rapamycin (mTOR), p38, JNK and ERK MAPK, Akt, and NF-kappaB were significantly increased by combining HPE and MTA compared with MTA alone. Pulp capping with MTA plus HPE in rats showed superior dentin bridge formation, odontoblastic layers and dentinal tubules and lower inflammatory cell response, compared to the MTA alone group. CONCLUSIONS: This study demonstrates for the first time that the use of MTA with HPE promotes cell growth, differentiation and angiogenesis in HDPCs, which were associated with mTOR, MAPK and NF-kappaB pathways. Direct pulp capping with HPE plus MTA showed superior results when compared with MTA alone. Thus, the combination of MTA and HPE may be useful for regenerative endodontics. PMID- 26807657 TI - Mechanism of Synergistic Cu(II)/Cu(I)-Mediated Alkyne Coupling: Dinuclear 1,2 Reductive Elimination after Minimum Energy Crossing Point. AB - An in-depth theoretical study of synergistic Cu(II)/Cu(I)-mediated alkyne coupling was performed to reveal the detailed mechanism for C-C bond formation, which proceeded via an unusual dinuclear 1,2-reductive elimination. Because the reactant for dinuclear 1,2-reductive elimination was calculated to be triplet while the products were singlet, the minimum energy crossing point (MECP) was introduced to the Cu/TMEDA/alkyne system to clarify the spin crossing between triplet state and singlet state potential energy surfaces. Computational results suggest that C-H bond cleavage solely catalyzed by the Cu(I) cation is the rate determining step of this reaction and Cu(II)-mediated dinuclear 1,2-reductive elimination after the MECP is a facile process. These conclusions are in good agreement with our previous experimental results. PMID- 26807658 TI - Interaction between Polymeric Additives and Secondary Fluids in Capillary Suspensions. AB - Capillary suspensions are ternary systems including a solid and two liquid phases representing a novel formulation platform for pastes with unique processing and end-use properties. Here we have investigated aqueous suspensions of non-Brownian graphite particles including different polymers commonly used as thickening agents or binders in paste formulations. We have studied the interaction between these additives and organic solvents in order to elucidate its effect on the characteristic formation of a particle network structure in corresponding ternary capillary suspension systems. Organic solvents with different polarity have been employed, and in the presence of nonadsorbing poly(ethylene oxide), all of them, whether they preferentially wet the graphite surface or not, induce the formation of a network structure within the suspension as indicated by a strong change in rheological properties. However, when the adsorbing polymers carboxymethylcellulose and poly(vinylpyrrolidone) are included, the drastic change in rheological behavior occurs only when polar organic solvents are used as secondary liquids. Obviously, these solvents can form pendular bridges, finally resulting in a sample-spanning particle network. Vibrational sum frequency spectroscopy provides evidence that these polar liquids remove the adsorbed polymer from the graphite particles. In contrast, nonpolar and nonwetting solvents do not force polymer desorption. In these cases, the formation of a percolating network structure within the suspensions is presumably prevented by the strong steric repulsion among graphite particles, not allowing for the formation of particle clusters encapsulating the secondary liquid. Accordingly, polymeric additives and secondary fluids have to be carefully selected in capillary suspension formulations, then offering a new pathway to customize paste formulations. The polymer may serve to adjust an appropriate viscosity level, and the capillary bridging induces the desired degree of shear thinning. Alternatively, the polymer may be selected with respect to its binding properties in the final dry product, and capillary bridging may be used to control the flow and processing behavior of the wet paste. PMID- 26807659 TI - Nonplasmonic Hot-Electron Photocurrents from Mn-Doped Quantum Dots in Photoelectrochemical Cells. AB - We report the measurement of the hot-electron current in a photoelectrochemical cell constructed from a glass/ITO/Al2 O3 (ITO=indium tin oxide) electrode coated with Mn-doped quantum dots, where hot electrons with a large excess kinetic energy were produced through upconversion of the excitons into hot electron hole pairs under photoexcitation at 3 eV. In our recent study (J. Am. Chem. Soc. 2015, 137, 5549), we demonstrated the generation of hot electrons in Mn-doped II-VI semiconductor quantum dots and their usefulness in photocatalytic H2 production reaction, taking advantage of the more efficient charge transfer of hot electrons compared with band-edge electrons. Here, we show that hot electrons produced in Mn-doped CdS/ZnS quantum dots possess sufficient kinetic energy to overcome the energy barrier from a 5.4-7.5 nm thick Al2 O3 layer producing a hot-electron current in photoelectrochemical cell. This work demonstrates the possibility of harvesting hot electrons not only at the interface of the doped quantum dot surface, but also far away from it, thus taking advantage of the capability of hot electrons for long-range electron transfer across a thick energy barrier. PMID- 26807660 TI - Extremely low frequency magnetic fields regulate differentiation of regulatory T cells: Potential role for ROS-mediated inhibition on AKT. AB - Our previous studies showed that extremely low frequency magnetic fields (ELF MFs) inhibited tumor growth and change proportion of splenic regulatory T cells (Treg cells). Here, we focus on the effect of ELF-MFs on lung metastatic melanoma mouse model and the regulatory mechanism of ELF-MFs on the differentiation of Treg cells. Tumor-bearing mice were exposed to sham ELF-MFs and ELF-MFs (0.4 T, 7.5 Hz) 2 h/day for 27 days. Metastatic tumor burden of lung was significantly decreased after ELF-MF treatment. Compared to the control group, expressions of matrix metalloproteinase (MMP2, MMP9) and forkhead box P3 (Foxp3) in lung nodules significantly decreased in the ELF-MF group. Moreover, in vitro, after stimulated with anti-CD3, anti-CD28 antibodies and transforming growth factor-beta (TGF beta) and treated with ELF-MFs for 2 h, expression of Foxp3 in total T cells was significantly decreased. Differentiation rate of Treg cells was inhibited from 32.0% to 22.1% by ELF-MFs. Furthermore, reactive oxygen species (ROS) was increased and phospho-serine/threonine protein kinase (p-AKT) was inhibited in both T cells and Jurkat cells. ROS scavenger N-acetyl-l-cysteine reversed inhibition of AKT pathway and expression of Foxp3 from 18.6% to 26.6% in T cells. Taken together, our data show that ELF-MF exposure promoted the inhibitory effect of ROS on AKT pathway and decreased Foxp3 expression, which provides an explanation for why ELF-MF exposure can inhibit differentiation of Treg cells and enhance antitumor effect in metastatic melanoma mouse model. PMID- 26807661 TI - Emergence of the First Catalytic Oligonucleotides in a Formamide-Based Origin Scenario. AB - 50 years after the historical Miller-Urey experiment, the formamide-based scenario is perhaps the most powerful concurrent hypothesis for the origin of life on our planet besides the traditional HCN-based concept. The information accumulated during the last 15 years in this topic is astonishingly growing and nowadays the formamide-based model represents one of the most complete and coherent pathways leading from simple prebiotic precursors up to the first catalytically active RNA molecules. In this work, we overview the major events of this long pathway that have emerged from recent experimental and theoretical studies, mainly concentrating on the mechanistic, methodological, and structural aspects of this research. PMID- 26807663 TI - Biomass-Derived Porous Carbon with Micropores and Small Mesopores for High Performance Lithium-Sulfur Batteries. AB - Biomass-derived porous carbon BPC-700, incorporating micropores and small mesopores, was prepared through pyrolysis of banana peel followed by activation with KOH. A high specific BET surface area (2741 m2 g-1 ), large specific pore volume (1.23 cm3 g-1 ), and well-controlled pore size distribution (0.6-5.0 nm) were obtained and up to 65 wt % sulfur content could be loaded into the pores of the BPC-700 sample. When the resultant C/S composite, BPC-700-S65, was used as the cathode of a Li-S battery, a large initial discharge capacity (ca. 1200 mAh g 1 ) was obtained, indicating a good sulfur utilization rate. An excellent discharge capacity (590 mAh g-1 ) was also achieved for BPC-700-S65 at the high current rate of 4 C (12.72 mA cm-2 ), showing its extremely high rate capability. A reversible capacity of about 570 mAh g-1 was achieved for BPC-700-S65 after 500 cycles at 1 C (3.18 mA cm-2 ), indicating an outstanding cycling stability. PMID- 26807662 TI - Development of Food-Grade Curcumin Nanoemulsion and its Potential Application to Food Beverage System: Antioxidant Property and In Vitro Digestion. AB - Curcumin nanoemulsions (Cur-NEs) were developed with various surfactant concentrations by using high pressure homogenization and finally applied to the commercial milk system. Characterization of Cur-NEs was performed by measuring the droplet size and polydispersity index value at different Tween 20 concentrations. The morphology of the Cur-NEs was observed by confocal laser scanning microscopy and transmission electron microscopy. Antioxidant activity and in vitro digestion ability were tested using 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, pH-stat method, and thiobarbituric acid reactive substances assays. Cur-NEs were found to be physically stable for 1 mo at room temperature. The surfactant concentration affects particle formation and droplet size. The mean droplet size decreased from 122 to 90 nm when surfactant concentration increased 3 times. Cur-NEs had shown an effective oxygen scavenging activity. Cur-NEs-fortified milk showed significantly lower lipid oxidation than control (unfortified) milk and milk containing curcumin-free nanoemulsions. These properties make Cur-NEs suitable systems for the beverage industry. PMID- 26807664 TI - Thermally Diffused Al:ZnO Thin Films for Broadband Transparent Conductor. AB - Here, we report an approach to realize highly transparent low resistance Al-doped ZnO (AZO) films for broadband transparent conductors. Thin Al films are deposited on ZnO surfaces, followed by thermal diffusion processes, introducing the Al doping into ZnO thin films. By utilizing the interdiffusion of Al, Zn, and O, the chemical state of Al on the surfaces can be converted to a fully oxidized state, resulting in a low sheet resistance of 6.2 Omega/sq and an excellent transparency (i.e., 96.5% at 550 nm and higher than 85% up to 2500 nm), which is superior compared with some previously reported values for indium tin oxide, solution processed AZO, and many transparent conducting materials using novel nanostructures. Such AZO films are also applied as transparent conducting layers for AZO/Si heterojunction solar cells, demonstrating their applications in optoelectronic devices. PMID- 26807665 TI - Tuning of Coupling and Surface Quality of PbS Nanocrystals via a Combined Ammonium Sulfide and Iodine Treatment. AB - Surface states of colloidal nanocrystals are typically created when organic surfactants are removed. We report a chemical process that reduces surface traps and tunes the interparticle coupling in PbS nanocrystal thin films after the surfactant ligands have been stripped off. This process produces PbS/PbI2 core/shell nanocrystal thin films via a combined ammonium sulfide and iodine treatment. These all-inorganic nanocrystal thin films are air-stable and exhibit bright emission with optimum photoluminescence quantum yield close to that of pristine PbS nanocrystals passivated by oleate ligands. Interparticle coupling of post-treatment nanocrystal thin films is continuously tunable by varying the iodine treatment process. Optical studies reveal that this method can produce PbS nanocrystal thin films superior in both coupling and surface quality to nanocrystals linked by small molecules such as ethanedithiol or 3 mercaptopropionic acid. PMID- 26807666 TI - Cognitive performance in depressed older persons: the impact of vascular burden and remission. A two-year follow-up study. AB - OBJECTIVES: Depression is associated with an increased risk of cognitive decline. The present study compared two-year change in cognitive performance between depressed older persons and a non-depressed control group, between remitted and non-remitted patients, and evaluated whether vascular burden at baseline was associated with more cognitive decline in depressed older persons. METHODS: Depressed patients (n = 378) aged >=60 were recruited from mental healthcare institutes and general practices, and a non-depressed control group (n = 132) was recruited from general practices. A DSM-IV depressive episode was established with the Composite International Diagnostic Interview, and processing speed, working memory, verbal memory and interference control were evaluated with three neurocognitive tasks at baseline and 2 years later. A modified Framingham Risk Score, ankle-brachial index, and history of a vascular event defined vascular burden at baseline. RESULTS: After adjusting for baseline cognitive performance, age, sex, and education level, depressed older persons had worse processing speed and verbal memory scores at follow-up than controls (regression coefficients: 0.172; p = 0.042 and -0.309; p = 0.001, respectively) but did not differ in the other two-cognitive outcomes. In the sample of depressed patients, remission status at 2 years follow-up and baseline vascular burden did not predict cognitive performance at follow-up, after adjustment for baseline cognitive performance, age, sex and education level. CONCLUSIONS: Our findings suggest that cognitive deficits in depressed older persons are not just a manifestation of depression. In addition, vascular burden was not associated with worse cognitive decline in a sample of depressed older persons. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26807667 TI - Applications of microfluidics in microalgae biotechnology: A review. AB - Microalgae have been one of the important sources for biofuel production owing to their competitive advantages such as no need to tap into the global food supply chain, higher energy density, and absorbing carbon dioxide to mitigate global warming. One of the key factors to ensure successful biofuel production is that it requires not only bioprospecting of the microalgae with high lipid content, high growth rate and tolerance to environmental parameters but also on-site monitoring of the cultivation process and optimization of the culturing conditions. However, as the conventional techniques usually involve in complicated procedures, or are time-consuming or labor intensive, microfluidics technology offers an attractive alternative to resolve these issues. In this review, applications of microfluidics to bioprospecting in microalgae biotechnology were discussed such as cell identification, cell sorting/screening, cell culturing and cell disruption. In addition, utilization of microalgae in micro-sized fuel cells and microfluidic platforms for biosensing was addressed. This review reports the recent studies and offers a look into how microfluidics is exploited to tackle the issues encountered in the microalgae biotechnology. PMID- 26807668 TI - Rifabutin Containing Triple Therapy and Rifabutin with Bismuth Containing Quadruple Therapy for Third-Line Treatment of Helicobacter pylori Infection: Two Pilot Studies. AB - AIM: To evaluate the therapeutic gain of the addition of bismuth to a rifabutin containing triple therapy with amoxicillin and pantoprazole at standard dosages for the treatment of third-line Helicobacter pylori infection after a preliminary susceptibility test. METHODS: Two separate groups of patients in two pilot studies which were carried out simultaneously. One group was treated with rifabutin 150 mg b.i.d., pantoprazole 20 mg b.i.d., and amoxicillin 1 g b.i.d. for 10 days and the other group with rifabutin 150 mg b.i.d., pantoprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and bismuth subcitrate 240 mg b.i.d. for 10 days. All patients underwent to culture and susceptibility testing prior to their inclusion in the study. A successful outcome was confirmed with an Urea Breath test performed 8 weeks after the end of treatment. A blood cell count was performed for all patients at the start and after 5 days of treatment since rifabutin has been shown to inhibit the growth of leucocytes. RESULTS: Twenty nine patients were recruited in the pantoprazole, amoxicillin, rifabutin group and 30 in the pantoprazole, amoxicillin, rifabutin, and bismuth subcitrate group. All patients had a positive H. pylori culture and the susceptibility test used showed H. pylori sensitivity to rifabutin and amoxicillin. H. pylori eradication during follow-up was 18/27 (66.7%, 95% CI: 47.7-85.7%) in the pantoprazole, amoxicillin, rifabutin group and 28/29 (96.6%, 95% CI: 89.5-100.0%) in the pantoprazole, amoxicillin, rifabutin, and bismuth subcitrate group. Both treatments were well-tolerated with no reported side effects. Blood cell count remained normal in all patients. CONCLUSION: The addition of bismuth subcitrate to a triple therapy that includes proton pump inhibitors, amoxicillin, and rifabutin in patients who are treated for the third time for H. pylori infection resulted in a 30% therapeutic gain. PMID- 26807669 TI - Comment on "Reaction Coordinates and Pathways of Mechanochemical Transformations". PMID- 26807670 TI - Obesity, metabolic syndrome and Mediterranean diet: Impact on depression outcome. AB - OBJECTIVE: Obesity, metabolic syndrome (MetS) and low adherence to Mediterranean diet are frequent in major depression patients and have been separately related with prognosis. The aim of this study is to analyse their predictive power on major depression outcome, at 6 and 12 months. METHODS: 273 Major depressive patients completed the Beck Depression Inventory for depressive symptoms and the 14-item Mediterranean diet adherence score. MetS was diagnosed according to the International Diabetes Federation (IDF). RESULTS: At the baseline Mediterranean diet adherence was inversely associated with depressive symptoms (p=0.007). Depression response was more likely in those patients with normal weight (p=0.006) and not MetS (p=0.013) but it was not associated with Mediterranean diet adherence (p=0.625). Those patients with MetS and obesity were less likely to improve symptoms of depression than patients with obesity but not MetS. CONCLUSIONS: Obesity and MetS, but not low adherence to the Mediterranean diet at baseline, predicted a poor outcome of depression at 12 months. Our study suggests that MetS is the key factor that impacts negatively in depression prognosis, rather than obesity or diet. If this finding is confirmed, clinicians should be aware about MetS diagnosis and treatment in overweight depressed patients, especially if outcome is not being satisfactory enough. PMID- 26807671 TI - Preliminary comparison of plasma notch-associated microRNA-34b and -34c levels in drug naive, first episode depressed patients and healthy controls. AB - BACKGROUND: Major depressive disorder (MDD) is a common debilitating disease of unknown etiology. The expression of miRNA is closely related to depression and efficacy of antidepressant therapy. However, whether Notch-associated miRNAs expressions involved in first-episode of MDD are still unknown. METHODS: In this study, the expression levels of Notch1, Hes1 mRNA and 5 miRNAs (miR-369-3p, miR 34b-5p, miR-34c-5p, miR-381 and miR-107) in peripheral blood leukocytes of 32 MDD patients and 32 healthy controls were detected using qRT-PCR method. We also assessed the severity of depressive symptom, suicide risk level, negative life events and event-related potential P300. RESULTS: The expression levels of miR 34b-5p (62.49 as the median of cases group and 38.62 as median of control group) and miR-34c-5p (7.17 as the median of cases group and 5.45 as median of control group) in MDD patients were significantly higher than these in control subjects. NOTCH1 gene were significantly lower in MDD patients (5.35 as the median of cases group and 6.80 as median of control group), and was negatively correlated with the expression miR-34c-5p and miR-34b-5p. The expression level of miR-34b-5p and miR-369-3p were significantly lower in patients with suicide idea. N1 latency of P300 were positive correlated with miR-34c-5p, miR-107 and miR-381, and P2 latency of P300 were positive correlated with miR-34c-5p, miR-107 and miR-381. LIMITATIONS: The sample size was small and the role of candidate miRNAs in the regulation of Notch1 gene and cognitive function are still need to be further investigated. CONCLUSIONS: Differentially Notch-associated miRNAs expressions in peripheral blood might be involved in MDD, and the miR-34b-5p and miR-34c-5p levels in peripheral blood leukocytes are closely related to MDD, suicide idea and cognitive function, further studies with large sample size are warranted to test the feasibility of these miRNAs serving as biomarkers for MDD. PMID- 26807673 TI - Modified maximum tangential stress criterion for fracture behavior of zirconia/veneer interfaces. AB - The veneering porcelain sintered on zirconia is widely used in dental prostheses, but repeated mechanical loadings may cause a fracture such as edge chipping or delamination. In order to predict the crack initiation angle and fracture toughness of zirconia/veneer bi-layered components subjected to mixed mode loadings, the accuracy of a new and traditional fracture criteria are investigated. A modified maximum tangential stress criterion considering the effect of T-stress and critical distance theory is introduced, and compared to three traditional fracture criteria. Comparisons to the recently published fracture test data show that the traditional fracture criteria are not able to properly predict the fracture initiation conditions in zirconia/veneer bi material joints. The modified maximum tangential stress criterion provides more accurate predictions of the experimental results than the traditional fracture criteria. PMID- 26807672 TI - An assessment of the anti-fatigue effects of ketamine from a double-blind, placebo-controlled, crossover study in bipolar disorder. AB - BACKGROUND: Fatigue is a multidimensional condition that is difficult to treat with standard monoaminergic antidepressants. Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist produces rapid and robust improvements in depressive symptoms in treatment-resistant depression. However, there is a dearth of literature examining the anti-fatigue effects of ketamine. We hypothesize that ketamine will rapidly improve fatigue symptoms in treatment-resistant depressed patients. METHODS: This is an exploratory analysis of data obtained from two double-blind, randomized, placebo-controlled, crossover trials. A total of 36 participants with treatment-resistant bipolar I or II disorder in a depressive episode (maintained on therapeutic levels of lithium or valproate) received a single infusion of ketamine hydrochloride intravenously (0.5 mg/kg over 40 min) or placebo. A post-hoc analysis compared fatigue scores on ketamine vs. placebo at 10 time points from baseline through 14 days post-treatment using the National Institute of Health-Brief Fatigue Inventory. RESULTS: A linear mixed model showed that ketamine significantly lowered fatigue scores compared to placebo from 40 min post-treatment to Day 14 with the exception of Day 7. The largest difference in anti-fatigue effects between placebo and ketamine was at day 2 (d=0.58, p<0.05). The effect remained significant after controlling for changes in non fatigue depressive symptoms. LIMITATION: The retrospective nature and a small sample size are study limitations. CONCLUSIONS: Ketamine rapidly improved fatigue relative to placebo in a group of individuals with treatment-resistant bipolar depression. NMDAR is a glutamate receptor; hence, glutamate may represent a valuable target to study the clinical efficacy of new anti-fatigue approaches in multiple disorders. PMID- 26807674 TI - Targeted and non-targeted detection of lemon juice adulteration by LC-MS and chemometrics. AB - Economically motivated adulteration (EMA) of lemon juice was detected by LC-MS and principal component analysis (PCA). Twenty-two batches of freshly squeezed lemon juice were adulterated by adding an aqueous solution containing 5% citric acid and 6% sucrose to pure lemon juice to obtain 30%, 60% and 100% lemon juice samples. Their total titratable acidities, degrees Brix and pH values were measured, and then all the lemon juice samples were subject to LC-MS analysis. Concentrations of hesperidin and eriocitrin, major phenolic components of lemon juice, were quantified. The PCA score plots for LC-MS datasets were used to preview the classification of pure and adulterated lemon juice samples. Results showed a large inherent variability in the chemical properties among 22 batches of 100% lemon juice samples. Measurement or quantitation of one or several chemical properties (targeted detection) was not effective in detecting lemon juice adulteration. However, by using the LC-MS datasets, including both chromatographic and mass spectrometric information, 100% lemon juice samples were successfully differentiated from adulterated samples containing 30% lemon juice in the PCA score plot. LC-MS coupled with chemometric analysis can be a complement to existing methods for detecting juice adulteration. PMID- 26807675 TI - Spectrum of Choroidal Involvement in Presumed Ocular Tuberculosis: Report from a Population with Low Endemic Setting for Tuberculosis. AB - OBJECTIVE: To describe the clinical spectrum and outcome of patients with presumed tubercular uveitis and choroidal involvement. METHODS: A retrospective case series nested in a cohort study was enrolled at a tertiary referral eye care center in the UK. Failure was defined as recurrence of lesion within 6 months of completion of antitubercular therapy (ATT) or corticosteroid therapy. RESULTS: Seventy-seven patients with presumed ocular tuberculosis and choroidal involvement were included in the study. Mean age was 45.5 +/- 15.7 years, 44 (57.1%) patients were male, and 51 (66.2%) presented with bilateral disease. Choroidal granuloma was the most frequent clinical presentation (n = 27, 35.07%), followed by multifocal choroiditis (n = 24, 31.17%) and serpiginous-like choroiditis (n = 18, 23.38%). Quantiferon Gold in Tube Test (QFT) was positive in 64 (83.11%) patients. Fifty (64.94%) patients received ATT. CONCLUSIONS: Choroidal involvement in presumed ocular tuberculosis can present with a variable spectrum. Treatment failure rates were equivalent between ATT and non-ATT treated groups. PMID- 26807676 TI - Inter-comparison of radon detectors for one to four week measurement periods. AB - Seven different types of radon detectors (Atmos 12 dpx, RAD7, RStone, Sun Nuclear 1028, Ramon 2.2, Canary and CR-39) were compared for exposure periods of 1, 2, 3 and 4 weeks. The comparison was conducted under two conditions: (a) in a purpose built radon chamber with an average radon concentration of 2560 Bq m(-3) (b) in a home environment with a radon concentration of 57 Bq m(-3), in both cases measured by the reference detector (Atmos 12 dpx) with a +/-10% uncertainty range. In (a) 5 out of 8 detectors recorded radon concentrations within the Atmos uncertainty range and all detectors recorded within +/-15%; in (b) 3 out of 9 detectors recorded within the Atmos uncertainty range and 6 out of 9 measured within +/-20%, for a 4 week measurement. The results from this study show that radon surveys can be conducted for shorter periods than the recommended 3 months where a rapid indication is needed of whether the radon concentration is above the reference level, such as when assessing the concentration during and after remediation work. PMID- 26807677 TI - Substituted Septithiophenes with End Groups of Different Size: Packing and Frustration in Bulk and Thin Films. AB - We report on three different liquid crystalline compounds with a central septithiophene core and alkylated end groups of strongly increasing bulkiness. In principle, the thiophene cores prefer to pack parallel to optimize their pi-pi interactions, which becomes sterically impossible for the bulkier end groups. Using X-ray diffraction, we find that the way out of this packing dilemma is toward liquid-crystal phases of higher dimensionality in the order smectic -> columnar <-> bicontinuous cubic. For the smectic phase, packing in a monolayer is no problem; for the other ones packing considerations become more stringent in films due to the boundaries. Surface X-ray techniques and atomic force microscopy indicate an appreciable difference between monolayer and three-layer films, in which the monolayers appear to escape from packing frustration by generating superstructures. We propose a basic structure of columns parallel to the substrate that provides a compromise between preserving some pi-pi interactions and packing the bulky alkyl groups. PMID- 26807678 TI - Preparation of Inert Polystyrene Latex Particles as MicroRNA Delivery Vectors by Surfactant-Free RAFT Emulsion Polymerization. AB - We present the preparation of 11 nm polyacrylamide-stabilized polystyrene latex particles for conjugation to a microRNA model by surfactant-free RAFT emulsion polymerization. Our synthetic strategy involved the preparation of amphiphilic polyacrylamide-block-polystyrene copolymers, which were able to self-assemble into polymeric micelles and "grow" into polystyrene latex particles. The surface of these sterically stabilized particles was postmodified with a disulfide bearing linker for the attachment of the microRNA model, which can be released from the latex particles under reducing conditions. These nanoparticles offer the advantage of ease of preparation via a scaleable process, and the versatility of their synthesis makes them adaptable to a range of applications. PMID- 26807679 TI - Hydrodynamic fabrication of structurally gradient ZnO nanorods. AB - We studied a new approach where structurally gradient nanostructures were fabricated by means of hydrodynamics. Zinc oxide (ZnO) nanorods were synthesized in a drag-driven rotational flow in a controlled manner. The structural characteristics of nanorods such as orientation and diameter were determined by momentum and mass transfer at the substrate surface. The nucleation of ZnO was induced by shear stress which plays a key role in determining the orientation of ZnO nanorods. The nucleation and growth of such nanostructures were modeled theoretically and analyzed numerically to understand the underlying physics of the fabrication of nanostructures controlled by hydrodynamics. The findings demonstrated that the precise control of momentum and mass transfer enabled the formation of ZnO nanorods with a structural gradient in diameter and orientation. PMID- 26807680 TI - A DFT Study on the Conversion of Aryl Iodides to Alkyl Iodides: Reductive Elimination of R-I from Alkylpalladium Iodide Complexes with Accessible beta Hydrogens. AB - DFT calculations have been performed on the palladium-catalyzed carboiodination reaction. The reaction involves oxidative addition, alkyne insertion, C-N bond cleavage, and reductive elimination. For the alkylpalladium iodide intermediate, LiOtBu stabilizes the intermediate in non-polar solvents, thus promoting reductive elimination and preventing beta-hydride elimination. The C-N bond cleavage process was explored and the computations show that PPh3 is not bound to the Pd center during this step. Experimentally, it was demonstrated that LiOtBu is not necessary for the oxidative addition, alkyne insertion, or C-N bond cleavage steps, lending support to the conclusions from the DFT calculations. The turnover-limiting steps were found to be C-N bond cleavage and reductive elimination, whereas oxidative addition, alkyne insertion, and formation of the indole ring provide the driving force for the reaction. PMID- 26807681 TI - Long-Term Outcomes in Critically Ill Septic Patients Who Survived Cardiopulmonary Resuscitation. AB - OBJECTIVE: To evaluate the long-term survival rate of critically ill sepsis survivors following cardiopulmonary resuscitation on a national scale. DESIGN: Retrospective and observational cohort study. SETTING: Data were extracted from Taiwan's National Health Insurance Research Database. PATIENTS: A total of 272,897 ICU patients with sepsis were identified during 2000-2010. Patients who survived to hospital discharge were enrolled. Post-discharge survival outcomes of ICU sepsis survivors who received cardiopulmonary resuscitation were compared with those of patients who did not experience cardiopulmonary arrest using propensity score matching with a 1:1 ratio. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Only 7% (n = 3,207) of sepsis patients who received cardiopulmonary resuscitation survived to discharge. The overall 1-, 2-, and 5-year postdischarge survival rates following cardiopulmonary resuscitation were 28%, 23%, and 14%, respectively. Compared with sepsis survivors without cardiopulmonary arrest, sepsis survivors who received cardiopulmonary resuscitation had a greater risk of all-cause mortality after discharge (hazard ratio, 1.38; 95% CI, 1.34-1.46). This difference in mortality risk diminished after 2 years (hazard ratio, 1.11; 95% CI, 0.96-1.28). Multivariable analysis showed that independent risk factors for long-term mortality following cardiopulmonary resuscitation were male sex, older age, receipt of care in a nonmedical center, higher Charlson Comorbidity Index score, chronic kidney disease, cancer, respiratory infection, vasoactive agent use, and receipt of renal replacement therapy during ICU stay. CONCLUSION: The long-term outcome was worse in ICU survivors of sepsis who received in-hospital cardiopulmonary resuscitation than in those who did not, but this increased risk of mortality diminished at 2 years after discharge. PMID- 26807682 TI - A Pilot Randomized Trial Comparing Weaning From Mechanical Ventilation on Pressure Support Versus Proportional Assist Ventilation. AB - OBJECTIVES: Despite protocols incorporating spontaneous breathing trials, 31% of ICU patients experience difficult or prolonged weaning from mechanical ventilation. Nonfatiguing modes such as pressure support ventilation are recommended. Proportional assist ventilation provides assistance in proportion to patient effort, which may optimize weaning. However, it is not known how proportional assist ventilation performs relative to pressure support ventilation over a prolonged period in the complex ICU setting. The purpose of this study was to compare the physiologic and clinical performance (failure rate), safety, and feasibility of protocols using daily spontaneous breathing trial plus pressure support ventilation versus proportional assist ventilation until ventilation discontinuation. DESIGN: Single-center, unblinded pilot randomized controlled trial. SETTING: Medical-surgical ICU of a tertiary-care hospital. PATIENTS: Adult patients intubated greater than 36 hours were randomized if they met eligibility criteria for partial ventilatory support, tolerated pressure support ventilation greater than or equal to 30 minutes, and either failed or did not meet criteria for a spontaneous breathing trial. INTERVENTIONS: Patients were randomized to the pressure support ventilation or proportional assist ventilation protocol (PAV+, Puritan Bennett 840; Covidien, Boulder, CO). Both protocols used progressive decreases in level of assistance as tolerated, coupled with daily assessment for spontaneous breathing trials. MEASUREMENTS AND MAIN RESULTS: Of 54 patients randomized, outcome data are available for 50 patients; 27 were randomized to receive proportional assist ventilation and 23 to receive pressure support ventilation. There were no adverse events linked to the study interventions, and protocol violations were infrequent. Recruitment was slower than projected (1.3 patients per month). The median (interquartile range) time from randomization to successful extubation was 3.9 days (2.8-8.4 d) on proportional assist ventilation versus 4.9 days (2.9-26.3 d) on pressure support ventilation (p = 0.39). Time to live ICU discharge was 7.3 days (5.2-11.4 d) on proportional assist ventilation versus 12.4 days (7.5-30.8 d) on pressure support ventilation (p = 0.03). CONCLUSION: This pilot study demonstrates the utility, safety, and feasibility of the weaning protocols and provides important information to guide the design of a future randomized controlled trial comparing weaning from mechanical ventilation on pressure support ventilation versus proportional assist ventilation. PMID- 26807684 TI - Outcomes of Protocol-Driven Care of Critically Ill Severely Anemic Patients for Whom Blood Transfusion Is Not an Option. AB - OBJECTIVE: To compare the outcomes of severely anemic critically ill patients for whom transfusion is not an option ("bloodless" patients) with transfused patients. DESIGN: Cohort study with propensity score matching. SETTING: ICU of a referral center. PATIENTS: One hundred seventy-eight bloodless and 441 transfused consecutive severely anemic, critically ill patients, admitted between May 1996 and April 2011, and having at least one hemoglobin level less than or equal to 8 g/dL within 24 hours of ICU admission. Patients with diagnosis of brain injury, acute myocardial infarction, or status postcardiac surgery were excluded. INTERVENTIONS: Allogeneic RBC transfusion during ICU stay. MEASUREMENTS AND MAIN RESULTS: Primary outcome was in-hospital mortality. Other outcomes were ICU mortality, readmission to ICU, new electrocardiographic or cardiac enzyme changes suggestive of cardiac ischemia or injury, and new positive blood culture result. Transfused patients were older, had higher hemoglobin level at admission, and had higher Acute Physiology and Chronic Health Evaluation II score. Hospital mortality rates were 24.7% in bloodless and 24.5% in transfused patients (odds ratio, 1.01; 95% CI, 0.68-1.52; p = 0.95). Adjusted odds ratio of hospital mortality was 1.52 (95% CI, 0.95-2.43; p = 0.08). No significant difference in ICU readmission or positive blood culture results was observed. Analysis of propensity score-matched cohorts provided similar results. CONCLUSIONS: Overall risk of mortality in severely anemic critically ill bloodless patients appeared to be comparable with transfused patients, albeit the latter group had older age and higher Acute Physiology and Chronic Health Evaluation II score. Use of a protocol to manage anemia in these patients in a center with established patient blood management and bloodless medicine and surgery programs is feasible and likely to contribute to improved outcome, whereas more studies are needed to better delineate the impact of such programs. PMID- 26807683 TI - Epidemiology of Acute Respiratory Distress Syndrome Following Hematopoietic Stem Cell Transplantation. AB - OBJECTIVES: Pulmonary complications are common following hematopoietic stem cell transplantation. Numerous idiopathic post-transplantation pulmonary syndromes have been described. Patients at the severe end of this spectrum may present with hypoxemic respiratory failure and pulmonary infiltrates, meeting criteria for acute respiratory distress syndrome. The incidence and outcomes of acute respiratory distress syndrome in this setting are poorly characterized. DESIGN: Retrospective cohort study. SETTING: Mayo Clinic, Rochester, MN. PATIENTS: Patients undergoing autologous and allogeneic hematopoietic stem cell transplantation between January 1, 2005, and December 31, 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were screened for acute respiratory distress syndrome development within 1 year of hematopoietic stem cell transplantation. Acute respiratory distress syndrome adjudication was performed in accordance with the 2012 Berlin criteria. In total, 133 cases of acute respiratory distress syndrome developed in 2,635 patients undergoing hematopoietic stem cell transplantation (5.0%). Acute respiratory distress syndrome developed in 75 patients (15.6%) undergoing allogeneic hematopoietic stem cell transplantation and 58 patients (2.7%) undergoing autologous hematopoietic stem cell transplantation. Median time to acute respiratory distress syndrome development was 55.4 days (interquartile range, 15.1-139 d) in allogeneic hematopoietic stem cell transplantation and 14.2 days (interquartile range, 10.5-124 d) in autologous hematopoietic stem cell transplantation. Twenty eight-day mortality was 46.6%. At 12 months following hematopoietic stem cell transplantation, 89 patients (66.9%) who developed acute respiratory distress syndrome had died. Only 7 of 133 acute respiratory distress syndrome cases met criteria for engraftment syndrome and 15 for diffuse alveolar hemorrhage. CONCLUSIONS: Acute respiratory distress syndrome is a frequent complication following hematopoietic stem cell transplantation, dramatically influencing patient-important outcomes. Most cases of acute respiratory distress syndrome following hematopoietic stem cell transplantation do not meet criteria for a more specific post-transplantation pulmonary syndrome. These findings highlight the need to better understand the risk factors underlying acute respiratory distress syndrome in this population, thereby facilitating the development of effective prevention strategies. PMID- 26807685 TI - Intracardiac Right-to-Left Shunt Impeding Liberation From Veno-Venous Extracorporeal Membrane Oxygenation: Two Case Studies. AB - OBJECTIVES: Veno-venous extracorporeal membrane oxygenation is an increasingly used form of advanced respiratory support, but its effects on the physiology of the right heart are incompletely understood. We seek to illustrate the impact of veno-venous extracorporeal membrane oxygenation return blood flow upon the right atrium by considering the physiologic effects during interatrial shunting. PATIENTS: Two veno-venous extracorporeal membrane oxygenation patients in whom an extracorporeal membrane oxygenation induced right-to-left interatrial shunt appears to have created a barrier to liberation from extracorporeal support. CONCLUSIONS: Veno-venous extracorporeal membrane oxygenation return flow generates a high-pressure jet that has potential to exert focal pressure upon the intra-atrial septum. In patients with potential for interatrial flow, this may lead to a right-to-left shunt, which becomes physiologically apparent only when sweep gas flow is ceased. PMID- 26807687 TI - Withdrawal of Life-Sustaining Therapy in Patients With Intracranial Hemorrhage: Self-Fulfilling Prophecy or Accurate Prediction of Outcome? AB - OBJECTIVES: Withdrawal of life-sustaining therapy may lead to premature limitations of life-saving treatments among patients with intracranial hemorrhage, representing a self-fulfilling prophecy. We aimed to determine whether our algorithm for the withdrawal of life-sustaining therapy decision would accurately identify patients with a high probability of poor outcome, despite aggressive treatment. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Tertiary-care Neuro-ICU. PATIENTS: Intraparenchymal, subdural, and subarachnoid hemorrhage patients. INTERVENTIONS: Baseline demographics, clinical status, and hospital course were assessed to determine the predictors of in-hospital mortality and 12-month death/severe disability among patients receiving maximal therapy. Multivariable logistic regression models developed on maximal therapy patients were applied to patients who underwent withdrawal of life-sustaining therapy to predict their probable outcome had they continued maximal treatment. A validation cohort of propensity score-matched patients was identified from the maximal therapy cohort, and their predicted and actual outcomes compared. MEASUREMENTS AND MAIN RESULTS: Of 383 patients enrolled, there were 128 subarachnoid hemorrhage (33.4%), 134 subdural hematoma (35.0%), and 121 intraparenchymal hemorrhage (31.6%). Twenty-six patients (6.8%) underwent withdrawal of life-sustaining therapy and died, 41 (10.7%) continued maximal therapy and died in hospital, and 316 (82.5%) continued maximal therapy and survived to discharge. The median predicted probability of in-hospital death among withdrawal of life-sustaining therapy patients was 35% had they continued maximal therapy, whereas the median predicted probability of 12-month death/severe disability was 98%. In the propensity-matched validation cohort, 16 of 20 patients had greater than or equal to 80% predicted probability of death/severe disability at 12 months, matching the observed outcomes and supporting the strength and validity of our prediction models. CONCLUSIONS: The withdrawal of life-sustaining therapy decision may contribute to premature in hospital death in some patients who may otherwise have been expected to survive to discharge. However, based on probability models, nearly all of the patients who underwent withdrawal of life-sustaining therapy would have died or remained severely disabled at 12 months had maximal therapy been continued. Withdrawal of life-sustaining therapy may not represent a self-fulfilling prophecy. PMID- 26807688 TI - Denim production and silicosis. AB - PURPOSE OF REVIEW: Silicosis because of denim sandblasting emerged as a new cause of silicosis in Turkey in the mid-2000s, and the following years have brought new cases constituting an epidemic with fatal outcomes. Because silicosis is a preventable disease, all efforts should be focused on preventing exposure to crystalline silica and thus development of the disease. RECENT FINDINGS: Denim sandblasters are at a high risk of silicosis. Patients with silicosis because of denim sandblasting exhibit rapid disease progression, and many of the complications associated with silicosis, including death, appear to be unavoidable. Thus, understanding the damage mechanism underlying silicosis in the lungs may help introduce treatment options to delay or reverse the progression of the disease. Silicosis because of denim sandblasting remains an important global health concern, particularly in low and middle-income countries. SUMMARY: Clinicians should be aware of potential occupational diseases, such as silicosis because of denim sandblasting, in unrecognized areas. To achieve success in the prevention of silicosis, occupational hygiene measures for crystalline silica should be supported by campaigns to not use sandblasted jeans worldwide. PMID- 26807689 TI - Lung volume reduction of pulmonary emphysema: the radiologist task. AB - PURPOSE OF REVIEW: Several lung volume reduction (LVR) techniques have been increasingly evaluated in patients with advanced pulmonary emphysema, especially in the last decade. Radiologist plays a pivotal role in the characterization of parenchymal damage and, thus, assessment of eligibility criteria. This review aims to discuss the most common LVR techniques, namely LVR surgery, endobronchial valves, and coils LVR, with emphasis on the role of computed tomography (CT). RECENT FINDINGS: Several trials have recently highlighted the importance of regional quantification of emphysema by computerized CT-based segmentation of hyperlucent parenchyma, which is strongly recommended for candidates to any LVR treatment. In particular, emphysema distribution pattern and fissures integrity are evaluated to tailor the choice of the most appropriate LVR technique. Furthermore, a number of CT measures have been tested for the personalization of treatment, according to imaging detected heterogeneity of parenchymal disease. SUMMARY: CT characterization of heterogeneous parenchymal abnormalities provides criteria for selection of the preferable treatment in each patient and improves outcome of LVR as reflected by better quality of life, higher exercise tolerance, and lower mortality. PMID- 26807690 TI - Desmin, desminopathy and the complexity of genetics. PMID- 26807686 TI - Psychiatric Symptoms in Acute Respiratory Distress Syndrome Survivors: A 1-Year National Multicenter Study. AB - OBJECTIVE: To evaluate prevalence, severity, and co-occurrence of and risk factors for depression, anxiety, and posttraumatic stress disorder symptoms over the first year after acute respiratory distress syndrome. DESIGN: Prospective longitudinal cohort study. SETTINGS: Forty-one Acute Respiratory Distress Syndrome Network hospitals across the United States. PATIENTS: Six hundred ninety eight acute respiratory distress syndrome survivors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Psychiatric symptoms were evaluated by using the Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised at 6 and 12 months. Adjusted prevalence ratios for substantial symptoms (binary outcome) and severity scores were calculated by using Poisson and linear regression, respectively. During 12 months, a total of 416 of 629 patients (66%) with at least one psychiatric outcome measure had substantial symptoms in at least one domain. There was a high and almost identical prevalence of substantial symptoms (36%, 42%, and 24% for depression, anxiety, and posttraumatic stress disorder) at 6 and 12 months. The most common pattern of co-occurrence was having symptoms of all three psychiatric domains simultaneously. Younger age, female sex, unemployment, alcohol misuse, and greater opioid use in the ICU were significantly associated with psychiatric symptoms, whereas greater severity of illness and ICU length of stay were not associated. CONCLUSIONS: Psychiatric symptoms occurred in two thirds of acute respiratory distress syndrome survivors with frequent co-occurrence. Sociodemographic characteristics and in-ICU opioid administration, rather than traditional measures of critical illness severity, should be considered in identifying the patients at highest risk for psychiatric symptoms during recovery. Given high co-occurrence, acute respiratory distress syndrome survivors should be simultaneously evaluated for a full spectrum of psychiatric sequelae to maximize recovery. PMID- 26807691 TI - Increased fibroblast chymase production mediates procollagen autophagic digestion in volume overload. AB - BACKGROUND: Previous work has identified mast cells as the major source of chymase largely associated with a profibrotic phenotype. We recently reported increased fibroblast autophagic procollagen degradation in a rat model of pure volume overload (VO). Here we demonstrate a connection between increased fibroblast chymase production and autophagic digestion of procollagen in the pure VO of aortocaval fistula (ACF) in the rat. METHODS AND RESULTS: Isolated LV fibroblasts taken from 4 and 12week ACF Sprague-Dawley rats have significant increases in chymase mRNA and chymase activity. Increased intracellular chymase protein is documented by immunocytochemistry in the ACF fibroblasts compared to cells obtained from age-matched sham rats. To implicate VO as a stimulus for chymase production, we show that isolated adult rat LV fibroblasts subjected to 24h of 20% cyclical stretch induces chymase mRNA and protein production. Exogenous chymase treatment of control isolated adult cardiac fibroblasts demonstrates that chymase is internalized through a dynamin-dependent mechanism. Chymase treatment leads to an increased formation of autophagic vacuoles, LC3-II production, autophagic flux, resulting in increased procollagen degradation. Chymase inhibitor treatment reduces cyclical stretch-induced autophagy in isolated cardiac fibroblasts, demonstrating chymase's role in autophagy induction. CONCLUSION: In a pure VO model, chymase produced in adult cardiac fibroblasts leads to autophagic degradation of newly synthesized intracellular procollagen I, suggesting a new role of chymase in extracellular matrix degradation. PMID- 26807693 TI - Radioprotective Agents: Strategies and Translational Advances. AB - Radioprotectors are agents required to protect biological system exposed to radiation, either naturally or through radiation leakage, and they protect normal cells from radiation injury in cancer patients undergoing radiotherapy. It is imperative to study radioprotectors and their mechanism of action comprehensively, looking at their potential therapeutic applications. This review intimately chronicles the rich intellectual, pharmacological story of natural and synthetic radioprotectors. A continuous effort is going on by researchers to develop clinically promising radioprotective agents. In this article, for the first time we have discussed the impact of radioprotectors on different signaling pathways in cells, which will create a basis for scientific community working in this area to develop novel molecules with better therapeutic efficacy. The bright future of exceptionally noncytotoxic derivatives of bisbenzimidazoles is also described as radiomodulators. Amifostine, an effective radioprotectant, has been approved by the FDA for limited clinical use. However, due to its adverse side effects, it is not routinely used clinically. Recently, CBLB502 and several analog of a peptide are under clinical trial and showed high success against radiotherapy in cancer. This article reviews the different types of radioprotective agents with emphasis on the strategies for the development of novel radioprotectors for drug development. In addition, direction for future strategies relevant to the development of radioprotectors is also addressed. PMID- 26807694 TI - Migratory diversity predicts population declines in birds. AB - Declines in migratory species are a pressing concern worldwide, but the mechanisms underpinning these declines are not fully understood. We hypothesised that species with greater within-population variability in migratory movements and destinations, here termed 'migratory diversity', might be more resilient to environmental change. To test this, we related map-based metrics of migratory diversity to recent population trends for 340 European breeding birds. Species that occupy larger non-breeding ranges relative to breeding, a characteristic we term 'migratory dispersion', were less likely to be declining than those with more restricted non-breeding ranges. Species with partial migration strategies (i.e. overlapping breeding and non-breeding ranges) were also less likely to be declining than full migrants or full residents, an effect that was independent of migration distance. Recent rates of advancement in Europe-wide spring arrival date were greater for partial migrants than full migrants, suggesting that migratory diversity may also help facilitate species responses to climate change. PMID- 26807695 TI - Persistent Premature Atrial Contraction as the Sole Presentation of Trigeminocardiac Reflex during Radiofrequency Thermocoagulation. PMID- 26807692 TI - Targeting therapeutic liabilities engendered by PIK3R1 mutations for cancer treatment. AB - The regulatory subunit of PI3K, p85alpha (encoded by PIK3R1), binds, stabilizes and inhibits the PI3K p110 catalytic subunit. Functional characterization of PIK3R1 mutations has identified not only hypomorphs with reduced inhibition of p110, but also hypomorphs and dominant negative mutants that disrupt a novel regulatory role of p85alpha on PTEN or neomorphs that activate unexpected signaling pathways. The diverse phenotypic spectrum of these PIK3R1 driver mutations underscores the need for different treatment strategies targeting tumors harboring these mutations. This article describes the functional consequences of the spectrum of PIK3R1 driver mutations and therapeutic liabilities they may engender. PMID- 26807696 TI - Laryngeal Mask Ventilation During Lumbar Spine Neurosurgery in Knee-Chest Position is Feasible. AB - BACKGROUND: This study describes our experience with laryngeal mask (LM) inserted after anesthetic induction in patients already in knee-chest position for lumbar neurosurgery. METHODS: Airway management (need for LM repositioning, orotracheal intubation because of failed LM insertion), anticipated difficult airway, and airway complications were registered. Statistics were compared between groups with the t test or the chi test, as appropriate. RESULTS: A total of 358 cases were reviewed from 2008 to 2013. Tracheal intubation was performed in 108 patients and LM was chosen for 250 patients (69.8%). Intubated patients had a higher mean age and rate of anticipated difficult airway; duration of surgery was longer (P<0.001, all comparisons). LM insertion and anesthetic induction proved effective in 97.2% of the LM-ventilated patients; 7 patients (2.8%) were intubated because of persistent leakage. Incidences with airway management were resolved without compromising patient safety. CONCLUSION: LM airway management during lumbar neurosurgery in knee-chest position is feasible for selected patients when the anesthetist is experienced. PMID- 26807697 TI - Degenerative Pathways of Lumbar Motion Segments--A Comparison in Two Samples of Patients with Persistent Low Back Pain. AB - BACKGROUND: Magnetic resonance imaging (MRI) is used to identify spinal pathoanatomy in people with persistent low back pain. However, the clinical relevance of spinal degenerative MRI findings remains uncertain. Although multiple MRI findings are almost always present at the same time, research into the association with clinical outcomes (such as pain) has predominantly focused on individual MRI findings. This study aimed to: (i) investigate how multiple MRI lumbar spine findings cluster together within two different samples of patients with low back pain, (ii) classify these clusters into hypothetical pathways of degeneration based on scientific knowledge of disco-vertebral degeneration, and (iii) compare these clusters and degenerative pathways between samples. METHODS: We performed a secondary cross-sectional analysis on two dissimilar MRI samples collected in a hospital department: (1) data from the spinal MRI reports of 4,162 low back pain patients and (2) data from an MRI research protocol of 631 low back pain patients. Latent Class Analysis was used in both samples to cluster MRI findings from lumbar motion segments. Using content analysis, each cluster was then categorised into hypothetical pathways of degeneration. RESULTS: Six clusters of MRI findings were identified in each of the two samples. The content of the clusters in the two samples displayed some differences but had the same overall pattern of MRI findings. Although the hypothetical degenerative pathways identified in the two samples were not identical, the overall pattern of increasing degeneration within the pathways was the same. CONCLUSIONS: It was expected that different clusters could emerge from different samples, however, when organised into hypothetical pathways of degeneration, the overall pattern of increasing degeneration was similar and biologically plausible. This evidence of reproducibility suggests that Latent Class Analysis may provide a new approach to investigating the relationship between MRI findings and clinically important characteristics such as pain and activity limitation. PMID- 26807698 TI - Detection of Different DNA Animal Species in Commercial Candy Products. AB - Candy products are consumed all across the world, but there is not much information about their composition. In this study we have used a DNA-based approach for determining the animal species occurring in 40 commercial candies of different types. We extracted DNA and performed PCR amplification, cloning and sequencing for obtaining species-informative DNA sequences. Eight species were identified including fish (hake and anchovy) in 22% of the products analyzed. Bovine and porcine were the most abundant appearing in 27 samples each one. Most products contained a mixture of species. Marshmallows (7), jelly-types, and gummies (20) contained a significantly higher number of species than hard candies (9). We demonstrated the presence of DNA animal species in candy product which allow consumers to make choices and prevent allergic reaction. PMID- 26807699 TI - Moral-up first, immoral-down last: the time course of moral metaphors on a vertical dimension. AB - Many abstract bipolar concepts are usually represented by metaphors on vertical dimensions (e.g. positive-up, negative-down). However, several studies have found an asymmetry in the way in which individuals process bipolar dimensions, with +polarities being stronger than -polarities. The current research focused on moral metaphors on a vertical dimension (e.g. moral-up and immoral-down) and examined the asymmetric representation of moral and immoral concepts. The first experiment showed a distinct metaphorical association between morality and vertical space, consistent with earlier research. The second experiment showed that moral and immoral words are processed differently depending on whether they are used as metaphorically congruent or incongruent vertical cues. 'Moral-up' association modulated the amplitudes of the N1, P2, and late positive-going potential during the processing of moral words, whereas the 'immoral-down' association only modulated the amplitudes of the late positive-going potential induced during the processing of immoral words. These results suggest that asymmetry in the processing of vertically represented morality metaphors is reflected in the time course of the representation of these bipolar concepts, with the 'moral-up' association having an earlier effect than the 'immoral-down' association. PMID- 26807700 TI - Kudos to COPE. PMID- 26807701 TI - Our Senior Editorial Reviewers: A Centerpiece. PMID- 26807702 TI - Direct detection of Mycobacterium tuberculosis in sputum: A validation study using solid phase extraction-gas chromatography-mass spectrometry. AB - Tuberculosis (TB) remains a worldwide health problem, especially in developing countries. Correct identification of Mycobacterium tuberculosis (MTB) infection is extremely important for providing appropriate treatment and care to patients. Here we describe a solid phase extraction-gas chromatography-mass spectrometry method (SPE-THM-GC-MS) for the detection of five biomarkers for M. tuberculosis. The method for classification is developed and validated through the analysis of 112 sputum samples from patients suspected of having TB. Twenty of twenty-five MTB culture-positive sputum samples were correctly classified as positive by our improved SPE-THM-GC-MS method. Eighty-five of eighty-seven MTB culture-negative samples were also negative by SPE-THM-GC-MS. The overall sensitivity of the new SPE-THM-GC-MS method is 80% (20/25) and the specificity is 98% (85/87) compared with culture. The method proved to be reliable and, although complex in principle, easy to operate due to the high degree of automation. PMID- 26807703 TI - Affinity purification of egg yolk immunoglobulins (IgY) using a human mycoplasma protein. AB - Egg yolk immunoglobulin (IgY) is a superior functional equivalent to mammalian IgG. However, the preparation of refined and highly purified IgY is still attributed as difficult task. Protein M (a transmembrane protein from human mycoplasma) has been newly demonstrated as an ideal affinity regent for mammalian antibody purification. This study aimed to evaluate the interaction between protein M and IgY. The results showed protein M could be a superior affinity reagent for IgY, scFv as well as IgYDeltaFc, based on pull down and western blot investigations; in addition, it was found that ~125 times increase of effective IgY in the elutent was obtained using protein M affinity chromatography column compared with traditional IgY extraction methods. This indicates, the purification strategy of protein M is entirely different to traditional IBPs and the salient purification feature of protein M would be a breakthrough for purifying not only non-mammalian antibodies, but also monoclonal antibodies and engineered antibodies based on variable region. PMID- 26807704 TI - Preparative separation of polyphenols from water-soluble fraction of Chinese propolis using macroporous absorptive resin coupled with preparative high performance liquid chromatography. AB - In this study, a preparative separation method was developed for isolation of eleven polyphenols from water-soluble fraction of Chinese propolis using macroporous absorptive resin (MAR) coupled with preparative high performance liquid chromatography (PHPLC). Water-soluble fraction of Chinese propolis was first "prefractioned" using MAR, which yielded four subfractions. The four subfractions were then isolated by PHPLC with an isocratic elution of methanol water. Finally, eleven polyphenols were purified from Chinese propolis including caffeic acid, ferulic acid, isoferulic acid, 3,4-dimethoxy cinnamic acid, pinobanksin, caffeic acid benzyl ester, caffeic acid phenethyl ester, apigenin, pinocembrin, chrysin and galangin. The purities of the compounds were determined by HPLC and the chemical structures were confirmed by UV and NMR analysis. The method developed was simple, effective, rapid, scalable and economical, and it was a promising basis for large-scale preparation of multiple components from natural products. PMID- 26807705 TI - Determination of ribavirin in chicken muscle by quick, easy, cheap, effective, rugged and safe method and liquid chromatography-tandem mass spectrometry. AB - A new analytical method for the determination of ribavirin in chicken muscle using a QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method and liquid chromatography-tandem mass spectrometry (LC-MS-MS) was developed and validated. Samples were extracted with acidified methanol (methanol:acetic acid, 99:1, v/v). The extract was further purified by QuEChERS method using primary secondary amine (PSA) and C18. Finally, the extract was dried by nitrogen under 45 degrees C and reconstituted in water. The separation was performed on a Hypercarb analytical column under a gradient elution. The mobile phase was composed of water buffered with ammonium acetate (2.0mM) and acetonitrile. The proposed method was validated according to the European Commission Decision 2002/657/EC. The values of the decision limit (CCalpha) and the detection capability (CCbeta) were 1.1 and 1.5MUg/kg, respectively. The mean recoveries of ribavirin ranged from 94.2% to 99.2%. The repeatability (expressed as coefficient of variation, CVr) of the method ranged from 4.5% to 4.9% and the reproducibility (CVR) of the method ranged from 4.8% to 5.4%. The method is demonstrated to be suitable for the determination of ribavirin in chicken muscle in conformity with the current EU performance requirements through validation. The total time required for the analysis of one sample, including sample preparation, was about 45min. PMID- 26807706 TI - UPLC-QTOFMS based metabolomics followed by stepwise partial least square discriminant analysis (PLS-DA) explore the possible relation between the variations in secondary metabolites and the phylogenetic divergences of the genus Panax. AB - Phylogenetic and metabolomic approaches have long been employed to study evolutionary relationships among plants. Nonetheless, few studies have examined the difference in metabolites within a clade and between clades of the phylogenetic tree. We attempted to relate phylogenetic studies to metabolomics using stepwise partial least squares-discriminant analysis (PLS-DA) for the genus Panax. Samples were analyzed by ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOFMS) to obtain metabolite profiles. Initially, conventional principal component analysis was subsequently applied to the metabolomic data to show the limitations in relating the expression of metabolites to divisions in the phylogenetic tree. Thereafter, we introduced stepwise PLS-DA with optimized scaling methods, which were properly applied according to the branches of the phylogenetic tree of the four species. Our approach highlighted metabolites of interest by elucidating the directions and degrees of metabolic alterations in each clade of the phylogenetic tree. The results revealed the relationship between metabolic changes in the genus Panax and its species' evolutionary adaptations to different climates. We believe our method will be useful to help understand the metabolite-evolution relationship. PMID- 26807707 TI - Application of alkyl polyglycoside surfactant in ultrasonic-assisted extraction followed by macroporous resin enrichment for the separation of vitexin-2"-O rhamnoside and vitexin from Crataegus pinnatifida leaves. AB - An alkyl polyglycoside (APG) surfactant was used in ultrasonic-assisted extraction to effectively extract vitexin-2"-O-rhamnoside (VOR) and vitexin (VIT) from Crataegus pinnatifida leaves. APG0810 was selected as the surfactant. The extraction process was optimized for ultrasonic power, the APG concentration, ultrasonic time, soaking time, and liquid-solid ratio. The proposed approach showed good recovery (99.80-102.50% for VOR and 98.83-103.19% for VIT) and reproducibility (relative standard deviation, n=5; 3.7% for VOR and 4.2% for VIT) for both components. The proposed sample preparation method is both simple and effective. The use of APG for extraction of key herbal ingredients shows great potential. Ten widely used commercial macroporous resins were evaluated in a screening study to identify a suitable resin for the separation and purification of VOR and VIT. After comparing static and dynamic adsorption and desorption processes, HPD100B was selected as the most suitable resin. After column adsorption and desorption on this resin, the target compounds VOR and VIT can be effectively separated from the APG0810 extraction solution. Recoveries of VOR and VIT were 89.27%+/-0.42% and 85.29%+/-0.36%, respectively. The purity of VOR increased from 35.0% to 58.3% and the purity of VIT increased from 12.5% to 19.9%. PMID- 26807708 TI - Self-Powered Broadband Photodetector using Plasmonic Titanium Nitride. AB - We report the demonstration of plasmonic titanium nitride (TiN) for fabrication of an efficient hybrid photodetector. A novel synthesis method based on plasma nanotechnology is utilized for producing air stable plasma polymerized aniline TiN (PPA-TiN) nanocomposite and its integration in photodetector geometry. The device performs as a self-powered detector that responds to ultraviolet and visible light at zero bias. The photodetector has the advantage of broadband absorption and outcomes an enhanced photoresponse including high responsivity and detectivity under low light conditions. This work opens up a new direction for plasmonic TiN-based hybrid nanocomposite and its exploitation in optoelectronic applications including imaging, light-wave communication and wire-free route for artificial vision. PMID- 26807709 TI - Prevalence of Neutralizing Antibodies to Japanese Encephalitis Virus among High Risk Age Groups in South Korea, 2010. AB - After an extensive vaccination policy, Japanese encephalitis (JE) was nearly eliminated since the mid-1980s in South Korea. Vaccination in children shifted the affected age of JE patients from children to adults. However, an abrupt increase in JE cases occurred in 2010, and this trend has continued. The present study aimed to investigate the prevalence of neutralizing antibodies to the JE virus (JEV) among high-risk age groups (>=40 years) in South Korea. A plaque reduction neutralization test was conducted to evaluate the prevalence of neutralizing antibodies to JEV in 945 subjects within four age groups (30-39, 40 49, 50-59, and 60-69 years) in 10 provinces. Of the 945 enrolled subjects, 927 (98.1%) exhibited antibodies against JEV. No significant differences were found in the prevalence of neutralizing antibodies according to sex, age, or occupation. However, there were significant differences in the plaque reduction rate according to age and occupation; oldest age group had a higher reduction rate, and subjects who were employed in agriculture or forestry also had a higher value than the other occupations. We also found that three provinces (Gangwon, Jeonnam, and Gyeongnam) had a relatively lower plaque reduction rate than the other locations. In addition, enzyme-linked immunosorbent assays were conducted to determine recent viral infections and 12 (1.3%) subjects were found to have been recently infected by the virus [corrected]. In conclusion, the present study clearly indicated that the prevalence of neutralizing antibodies has been maintained at very high levels among adult age groups owing to vaccination or natural infections, or both. In the future, serosurveillance should be conducted periodically using more representative samples to better understand the population-level immunity to JE in South Korea. PMID- 26807710 TI - A Simple and Non-Destructive Method for Assessing the Incorporation of Bipyridine Dicarboxylates as Linkers within Metal-Organic Frameworks. AB - As a novel avenue for applications, metal-organic frameworks (MOFs) are increasingly used for heterogenizing catalytic molecular species as linkers into their crystalline framework. These multifunctional compounds can be accessed with mixed linkers synthesis or postsynthetic-exchange strategies. Major limitations still reside in their challenging characterization; in particular, to provide evidence of the genuine incorporation of the functionalized linkers into the framework and their quantification. Herein, we demonstrate that a combination of computational chemistry, spectroscopy and X-ray diffraction allows access to a non-destructive analysis of mixed-linker UiO-67-type materials featuring biphenyl and bipyridine-dicarboxylates. Our UV/Vis-based methodology has been further applied to characterize a series of Rh-functionalized UiO-67-type catalysts. The proposed approach allows a recurrent key issue in the characterization of similar supported organometallic systems to be solved. PMID- 26807711 TI - Towards Plant Species Identification in Complex Samples: A Bioinformatics Pipeline for the Identification of Novel Nuclear Barcode Candidates. AB - Monitoring of the food chain to fight fraud and protect consumer health relies on the availability of methods to correctly identify the species present in samples, for which DNA barcoding is a promising candidate. The nuclear genome is a rich potential source of barcode targets, but has been relatively unexploited until now. Here, we show the development and use of a bioinformatics pipeline that processes available genome sequences to automatically screen large numbers of input candidates, identifies novel nuclear barcode targets and designs associated primer pairs, according to a specific set of requirements. We applied this pipeline to identify novel barcodes for plant species, a kingdom for which the currently available solutions are known to be insufficient. We tested one of the identified primer pairs and show its capability to correctly identify the plant species in simple and complex samples, validating the output of our approach. PMID- 26807713 TI - A Mobile Sensing Approach for Regional Surveillance of Fugitive Methane Emissions in Oil and Gas Production. AB - This paper addresses the need for surveillance of fugitive methane emissions over broad geographical regions. Most existing techniques suffer from being either extensive (but qualitative) or quantitative (but intensive with poor scalability). A total of two novel advancements are made here. First, a recursive Bayesian method is presented for probabilistically characterizing fugitive point sources from mobile sensor data. This approach is made possible by a new cross plume integrated dispersion formulation that overcomes much of the need for time averaging concentration data. The method is tested here against a limited data set of controlled methane release and shown to perform well. We then present an information-theoretic approach to plan the paths of the sensor-equipped vehicle, where the path is chosen so as to maximize expected reduction in integrated target source rate uncertainty in the region, subject to given starting and ending positions and prevailing meteorological conditions. The information-driven sensor path planning algorithm is tested and shown to provide robust results across a wide range of conditions. An overall system concept is presented for optionally piggybacking of these techniques onto normal industry maintenance operations using sensor-equipped work trucks. PMID- 26807712 TI - Kidney Function Decline and Apparent Treatment-Resistant Hypertension in the Elderly. AB - BACKGROUND: Cross-sectional studies show a strong association between chronic kidney disease and apparent treatment-resistant hypertension, but the longitudinal association of the rate of kidney function decline with the risk of resistant hypertension is unknown. METHODS: The population-based Three-City included 8,695 participants older than 65 years, 4265 of them treated for hypertension. We estimated the odds ratios (OR) of new-onset apparent treatment resistant hypertension, defined as blood pressure >= 140/90 mmHg despite use of 3 antihypertensive drug classes or >= 4 classes regardless of blood pressure, associated with the mean estimated glomerular filtration rate (eGFR) level and its rate of decline over 4 years, compared with both controlled hypertension and uncontrolled nonresistant hypertension with <= 2 drugs. GFR was estimated with three different equations. RESULTS: Baseline prevalence of apparent treatment resistant hypertension and of controlled and uncontrolled nonresistant hypertension, were 6.5%, 62.3% and 31.2%, respectively. During follow-up, 162 participants developed apparent treatment-resistant hypertension. Mean eGFR decline with the MDRD equation was 1.5+/-2.9 mL/min/1.73 m2 per year: 27.7% of the participants had an eGFR >=3 and 10.1% >= 5 mL/min/1.73 m2 per year. After adjusting for age, sex, obesity, diabetes, and cardiovascular history, the ORs for new-onset apparent treatment-resistant hypertension associated with a mean eGFR level, per 15 mL/min/1.73 m2 drop, were 1.23 [95% confidence interval 0.91 1.64] compared to controlled hypertension and 1.10 [0.83-1.45] compared to uncontrolled nonresistant hypertension; ORs associated with a decline rate >= 3 mL/min/1.73 m2 per year were 1.89 [1.09-3.29] and 1.99 [1.19-3.35], respectively. Similar results were obtained when we estimated GFR with the CKDEPI and the BIS1 equations. ORs tended to be higher for an eGFR decline rate >= 5 mL/min/1.73 m2 per year. CONCLUSION: The speed of kidney function decline is associated more strongly than kidney function itself with the risk of apparent treatment resistant hypertension in the elderly. PMID- 26807714 TI - A pyridoxal phosphate-dependent enzyme that oxidizes an unactivated carbon-carbon bond. AB - Pyridoxal 5'-phosphate (PLP)-dependent enzymes have wide catalytic versatility but are rarely known for their ability to react with oxygen to catalyze challenging reactions. Here, using in vitro reconstitution and kinetic analysis, we report that the indolmycin biosynthetic enzyme Ind4, from Streptomyces griseus ATCC 12648, is an unprecedented O2- and PLP-dependent enzyme that carries out a four-electron oxidation of L-arginine, including oxidation of an unactivated carbon-carbon (C-C) bond. We show that the conjugated product of this reaction, which is susceptible to nonenzymatic deamination, is efficiently intercepted and stereospecifically reduced by the partner enzyme Ind5 to give D-4,5 dehydroarginine. Thus, Ind4 couples the redox potential of O2 with the ability of PLP to stabilize anions to efficiently oxidize an unactivated C-C bond, with the subsequent stereochemical inversion by Ind5 preventing off-pathway reactions. Altogether, these results expand our knowledge of the catalytic versatility of PLP-dependent enzymes and enrich the toolbox for oxidative biocatalysis. PMID- 26807717 TI - Vibrational Quantum Decoherence in Liquid Water. AB - Traditional descriptions of vibrational energy transfer consider a quantum oscillator interacting with a classical environment. However, a major limitation of this simplified description is the neglect of quantum decoherence induced by the different interactions between two distinct quantum states and their environment, which can strongly affect the predicted energy-transfer rate and vibrational spectra. Here, we use quantum-classical molecular dynamics simulations to determine the vibrational quantum decoherence time for an OH stretch vibration in liquid heavy water. We show that coherence is lost on a sub 100 fs time scale due to the different responses of the first shell neighbors to the ground and excited OH vibrational states. This ultrafast decoherence induces a strong homogeneous contribution to the linear infrared spectrum and suggests that resonant vibrational energy transfer in H2O may be more incoherent than previously thought. PMID- 26807715 TI - A cellular chemical probe targeting the chromodomains of Polycomb repressive complex 1. AB - We report the design and characterization of UNC3866, a potent antagonist of the methyllysine (Kme) reading function of the Polycomb CBX and CDY families of chromodomains. Polycomb CBX proteins regulate gene expression by targeting Polycomb repressive complex 1 (PRC1) to sites of H3K27me3 via their chromodomains. UNC3866 binds the chromodomains of CBX4 and CBX7 most potently, with a K(d) of ~100 nM for each, and is 6- to 18-fold selective as compared to seven other CBX and CDY chromodomains while being highly selective over >250 other protein targets. X-ray crystallography revealed that UNC3866's interactions with the CBX chromodomains closely mimic those of the methylated H3 tail. UNC4195, a biotinylated derivative of UNC3866, was used to demonstrate that UNC3866 engages intact PRC1 and that EED incorporation into PRC1 is isoform dependent in PC3 prostate cancer cells. Finally, UNC3866 inhibits PC3 cell proliferation, consistent with the known ability of CBX7 overexpression to confer a growth advantage, whereas UNC4219, a methylated negative control compound, has negligible effects. PMID- 26807716 TI - A two-state activation mechanism controls the histone methyltransferase Suv39h1. AB - Specialized chromatin domains contribute to nuclear organization and regulation of gene expression. Gene-poor regions are di- and trimethylated at lysine 9 of histone H3 (H3K9me2 and H3K9me3) by the histone methyltransferase Suv39h1. This enzyme harnesses a positive feedback loop to spread H3K9me2 and H3K9me3 over extended heterochromatic regions. However, little is known about how feedback loops operate on complex biopolymers such as chromatin, in part because of the difficulty in obtaining suitable substrates. Here we describe the synthesis of multidomain 'designer chromatin' templates and their application to dissecting the regulation of human Suv39h1. We uncovered a two-step activation switch where H3K9me3 recognition and subsequent anchoring of the enzyme to chromatin allosterically promotes methylation activity and confirmed that this mechanism contributes to chromatin recognition in cells. We propose that this mechanism serves as a paradigm in chromatin biochemistry, as it enables highly dynamic sampling of chromatin state combined with targeted modification of desired genomic regions. PMID- 26807718 TI - Reduction of Oxidative Stress in Chronic Kidney Disease Does Not Increase Circulating alpha-Klotho Concentrations. AB - The CKD-associated decline in soluble alpha-Klotho levels is considered detrimental. Some in vitro and in vivo animal studies have shown that anti oxidant therapy can upregulate the expression of alpha-Klotho in the kidney. We examined the effect of anti-oxidant therapy on alpha-Klotho concentrations in a clinical cohort with mild tot moderate chronic kidney disease (CKD). We performed a post-hoc analysis of a prospective randomized trial involving 62 patients with mild to moderate CKD (the ATIC study), all using an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) for 12 months. On top of that, the intervention group received anti-oxidative therapy consisting of the combination of pravastatin (40 mg/d) and vitamin E (alpha-tocopherol acetate, 300 mg/d) while the placebo was not treated with anti-oxidants. alpha-Klotho concentrations were measured at baseline and after 12 months of anti-oxidant therapy. Data were analysed using T-tests and Generalized Estimating Equations, adjusting for potential confounders such as vitamin D, parathyroid hormone, fibroblast-growth-factor 23 (FGF23) and eGFR. The cohort existed of 62 patients with an eGFR (MDRD) of 35 +/- 14 ml/min/1.72 m2, 34 were male and mean age was 53.0 +/- 12.5 years old. Anti-oxidative therapy did successfully reduce oxLDL and LDL concentrations (P <0.001). alpha-Klotho concentrations did not change in patients receiving either anti-oxidative therapy (476.9 +/- 124.3 to 492.7 +/- 126.3 pg/mL, P = 0.23) nor in those receiving placebo 483.2 +/- 142.5 to 489.6 +/ 120.3 pg/mL, P = 0.62). Changes in alpha-Klotho concentrations were not different between both groups (p = 0.62). No evidence was found that anti oxidative therapy affected alpha-Klotho concentrations in patients with mild moderate CKD. PMID- 26807719 TI - The Effects of Empagliflozin, an SGLT2 Inhibitor, on Pancreatic beta-Cell Mass and Glucose Homeostasis in Type 1 Diabetes. AB - The novel sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin has recently been reported to improve glycemic control in streptozotocin-induced type 1 diabetic rats in an insulin-independent manner, via an increase in urinary glucose output. We investigated the potential of empagliflozin to recover insulin pathways in type 1 diabetes by improving pancreatic beta-cell mass. Blood glucose homeostasis was assessed by an intraperitoneal glucose tolerance test. Serum insulin levels and insulin mRNA expression were determined using commercial insulin ELISA kits and real-time quantitative polymerase chain reaction, respectively. Immunohistochemistry was used to investigate beta-cell areas, beta cell proliferation, apoptosis of pancreatic beta-cells, and reactive oxygen species production in the pancreatic beta-cells. Results showed that glucose tolerance was significantly improved in streptozotocin-induced type 1 diabetic mice treated with empagliflozin. Empagliflozin-treated mice also showed an increase in insulin mRNA expression. Higher serum insulin levels were detected in mice treated with empagliflozin compared with the vehicle group. Immunohistochemistry indicated that beta-cell area/total pancreatic area and the expression of cell proliferation marker Ki-67 (co-stained with insulin) were significantly enhanced by empagliflozin treatment. These effects were due, probably, to a reduction in apoptosis and reactive oxygen species in the pancreatic beta-cells. Taken together, the results of this study indicate that empagliflozin may have a beneficial effect on preserving beta-cell regeneration, thus improving blood glucose homeostasis in type 1 diabetes mellitus, probably via the protection of pancreatic beta-cell from glucotoxicity-induced oxidative stress. PMID- 26807720 TI - High Prevalence of West Nile Virus in Domestic Birds and Detection in 2 New Mosquito Species in Madagascar. AB - West Nile virus is an arthropod-borne zoonosis transmitted by a large number of mosquito species, and birds play a key role as reservoir of the virus. Its distribution is largely widespread over Africa, Asia, the Americas and Europe. Since 1978, it has frequently been reported in Madagascar. Studies described a high seroprevalence level of the virus in humans in different areas of the island and a human fatal case of WNV infection was reported in 2011. Despite these reports, the epidemiology of WNV in Madagascar, in particular, viral circulation remains unclear. To explore the transmission of WNV in two rural human populations of Madagascar, we investigated local mosquitoes and poultry for evidence of current infections, and determined seroprevalence of candidate sentinel species among the local poultry. These 2 areas are close to lakes where domestic birds, migratory wild birds and humans coexist. Serological analysis revealed WNV antibodies in domestic birds (duck, chicken, goose, turkey and guinea fowl) sampled in both districts (Antsalova 29.4% and Mitsinjo 16.7%). West Nile virus nucleic acid was detected in one chicken and in 8 pools of mosquitoes including 2 mosquito species (Aedeomyia madagascarica and Anopheles pauliani) that have not been previously described as candidate vectors for WNV. Molecular analysis of WNV isolates showed that all viruses detected were part of the lineage 2 that is mainly distributed in Africa, and were most closely matched by the previous Malagasy strains isolated in 1988. Our study showed that WNV circulates in Madagascar amongst domestic birds and mosquitoes, and highlights the utility of poultry as a surveillance tool to detect WNV transmission in a peri-domestic setting. PMID- 26807721 TI - Deletion of ASK1 Protects against Hyperoxia-Induced Acute Lung Injury. AB - Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAPK kinase kinase kinase (MAP3K) family, is activated by various stimuli, which include oxidative stress, endoplasmic reticulum (ER) stress, calcium influx, DNA damage-inducing agents and receptor-mediated signaling through tumor necrosis factor receptor (TNFR). Inspiration of a high concentration of oxygen is a palliative therapy which counteracts hypoxemia caused by acute lung injury (ALI)-induced pulmonary edema. However, animal experiments so far have shown that hyperoxia itself could exacerbate ALI through reactive oxygen species (ROS). Our previous data indicates that ASK1 plays a pivotal role in hyperoxia-induced acute lung injury (HALI). However, it is unclear whether or not deletion of ASK1 in vivo protects against HALI. In this study, we investigated whether ASK1 deletion would lead to attenuation of HALI. Our results show that ASK1 deletion in vivo significantly suppresses hyperoxia-induced elevation of inflammatory cytokines (i.e. IL-1beta and TNF-alpha), cell apoptosis in the lung, and recruitment of immune cells. In summary, the results from the study suggest that deletion of ASK1 in mice significantly inhibits hyperoxic lung injury. PMID- 26807722 TI - Fine-Scale Ecological and Genetic Population Structure of Two Whitefish (Coregoninae) Species in the Vicinity of Industrial Thermal Emissions. AB - Thermal pollution from industrial processes can have negative impacts on the spawning and development of cold-water fish. Point sources of thermal effluent may need to be managed to avoid affecting discrete populations. Correspondingly, we examined fine-scale ecological and genetic population structure of two whitefish species (Coregonus clupeaformis and Prosopium cylindraceum) on Lake Huron, Canada, in the immediate vicinity of thermal effluent from nuclear power generation. Niche metrics using delta13C and delta15N stable isotopes showed high levels of overlap (48.6 to 94.5%) in resource use by adult fish captured in areas affected by thermal effluent compared to nearby reference locations. Isotopic niche size, a metric of resource use diversity, was 1.3- to 2.8-fold higher than reference values in some thermally affected areas, indicative of fish mixing. Microsatellite analyses of genetic population structure (Fst, STRUCTURE and DAPC) indicated that fish captured at all locations in the vicinity of the power plant were part of a larger population extending beyond the study area. In concert, ecological and genetic markers do not support the presence of an evolutionarily significant unit in the vicinity of the power plant. Thus, future research should focus on the potential impacts of thermal emissions on development and recruitment. PMID- 26807723 TI - Lifitegrast, a Novel Integrin Antagonist for Treatment of Dry Eye Disease. AB - The etiology of dry eye disease (DED) is complex and not yet fully understood, but the disease is now recognized as being associated with ocular surface inflammation. The latest advances in the understanding of the pathophysiology of DED have directed the focus of recent drug development to target the inflammatory pathways involved in the disease. Lifitegrast is a novel small molecule integrin antagonist that inhibits T cell-mediated inflammation by blocking the binding of two important cell surface proteins (lymphocyte function-associated antigen 1 and intercellular adhesion molecule 1), thus lessening overall inflammatory responses. This review highlights the role of T cells and integrins in the inflammatory process involved in the pathophysiology of DED and outlines the scientific rationale for the role of lifitegrast. In addition, the preclinical development, pharmacological properties, clinical efficacy, and safety of lifitegrast are described. PMID- 26807724 TI - Dry Eye Profiles in Patients with a Positive Elevated Surface Matrix Metalloproteinase 9 Point-of-Care Test Versus Negative Patients. AB - PURPOSE: To compare dry eye (DE) symptoms and signs in subjects who tested positive versus those who tested negative for ocular surface matrix metalloproteinase 9 (MMP-9) using the InflammaDry point-of-care test (RPS, Sarasota, FL). METHODS: In this cross-sectional study, individuals seen in the Miami Veterans Affairs eye clinic with DE symptoms, as evidenced by DE questionnaire 5 (DEQ5) >=6, were given standardized questionnaires to assess DE symptoms and ocular and non-ocular pain complaints. Also, a complete evaluation was conducted to measure ocular surface signs of DE. MMP-9 testing was performed using the InflammaDry once in each eye, per the manufacturer's instructions. The main outcome measure was a comparison of DE symptoms and signs in MMP-9 positive versus negative subjects. RESULTS: Of 128 subjects, 50 (39%) were positive for MMP-9 for InflammaDry testing in either eye. No statistically significant differences in mental health indices, DE symptoms, or ocular surface signs were seen in subjects based on MMP-9 status. CONCLUSION: In our population, there was no difference in the DE profile by both symptoms and signs between those testing positive versus negative for MMP-9 on the ocular surface. This suggests that clinical exam alone cannot predict patients with clinically significant inflammation. PMID- 26807725 TI - Sp1 and Sp3 Are the Transcription Activators of Human ek1 Promoter in TSA-Treated Human Colon Carcinoma Cells. AB - BACKGROUND: Ethanolamine kinase (EK) catalyzes the phosphorylation of ethanolamine, the first step in the CDP-ethanolamine pathway for the biosynthesis of phosphatidylethanolamine (PE). Human EK exists as EK1, EK2alpha and EK2beta isoforms, encoded by two separate genes, named ek1 and ek2. EK activity is stimulated by carcinogens and oncogenes, suggesting the involvement of EK in carcinogenesis. Currently, little is known about EK transcriptional regulation by endogenous or exogenous signals, and the ek gene promoter has never been studied. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we mapped the important regulatory regions in the human ek1 promoter. 5' deletion analysis and site directed mutagenesis identified a Sp site at position (-40/-31) that was essential for the basal transcription of this gene. Treatment of HCT116 cells with trichostatin A (TSA), a histone deacetylase inhibitor, significantly upregulated the ek1 promoter activity through the Sp(-40/-31) site and increased the endogenous expression of ek1. Chromatin immunoprecipitation assay revealed that TSA increased the binding of Sp1, Sp3 and RNA polymerase II to the ek1 promoter in HCT116 cells. The effect of TSA on ek1 promoter activity was cell line specific as TSA treatment did not affect ek1 promoter activity in HepG2 cells. CONCLUSION/SIGNIFICANCE: In conclusion, we showed that Sp1 and Sp3 are not only essential for the basal transcription of the ek1 gene, their accessibility to the target site on the ek1 promoter is regulated by histone protein modification in a cell line dependent manner. PMID- 26807726 TI - Risk Factors for Normal and High-Tension Glaucoma in Poland in Connection with Polymorphisms of the Endothelial Nitric Oxide Synthase Gene. AB - AIM: The purpose of this study was to evaluate the influence of polymorphisms of the eNOS gene on the clinical status of patients with normal and high tension glaucoma. METHODS: 266 Polish Caucasian patients with primary open angle glaucoma were studied. Of the 266, 156 had normal tension glaucoma (NTG) and 110 high tension glaucoma (HTG). DNA material was isolated from peripheral venous blood using commercial kits. Real-time PCR reaction was used to amplify the promoter site of the endothelial nitric oxide synthase (eNOS) gene, including the single nucleotide polymorphism (SNP) site T-786C and part of the 7th exon of eNOS, including G894T SNP. Genotypes were determined with TaqMan SNP Genotyping Assays. RESULTS: There were no significant differences in frequencies of the allelic variants of both polymorphisms. In G894T SNP, however, the wild GG form was more common in the HTG group. The SNP of the eNOS gene did not significantly influence the progression rate in either of the groups studied. There were no differences in variants of the eNOS gene regarding the necessity for and success of surgery and the progression of the disease. In the NTG group, no statistical correlation was observed between G894T, T786C polymorphism variants, and risk factors such as optic disc haemorrhages, optic disc notches, and peripapillary atrophy. Mean diastolic and systolic pressure during the day and night were lowest in NTG patients with the CC variant of the T786C polymorphism. No statistical correlation was observed between the G894T and T786C polymorphisms and capillaroscopic examination results. CONCLUSIONS: Genotype frequencies are similar for both the eNOS G894T and T-786C polymorphisms in NTG and HTG patients. These polymorphisms do not correlate with risk factors and do not influence the state of the capillary system in NTG patients. Systolic blood pressure is lower in NTG patients with mutated alleles of both polymorphisms. PMID- 26807727 TI - Innovation of a Regulatory Mechanism Modulating Semi-determinate Stem Growth through Artificial Selection in Soybean. AB - It has been demonstrated that Terminal Flowering 1 (TFL1) in Arabidopsis and its functional orthologs in other plants specify indeterminate stem growth through their specific expression that represses floral identity genes in shoot apical meristems (SAMs), and that the loss-of-function mutations at these functional counterparts result in the transition of SAMs from the vegetative to reproductive state that is essential for initiation of terminal flowering and thus formation of determinate stems. However, little is known regarding how semi-determinate stems, which produce terminal racemes similar to those observed in determinate plants, are specified in any flowering plants. Here we show that semi-determinacy in soybean is modulated by transcriptional repression of Dt1, the functional ortholog of TFL1, in SAMs. Such repression is fulfilled by recently enabled spatiotemporal expression of Dt2, an ancestral form of the APETALA1/FRUITFULL orthologs, which encodes a MADS-box factor directly binding to the regulatory sequence of Dt1. In addition, Dt2 triggers co-expression of the putative SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (GmSOC1) in SAMs, where GmSOC1 interacts with Dt2, and also directly binds to the Dt1 regulatory sequence. Heterologous expression of Dt2 and Dt1 in determinate (tfl1) Arabidopsis mutants enables creation of semi-determinacy, but the same forms of the two genes in the tfl1 and soc1 background produce indeterminate stems, suggesting that Dt2 and SOC1 both are essential for transcriptional repression of Dt1. Nevertheless, the expression of Dt2 is unable to repress TFL1 in Arabidopsis, further demonstrating the evolutionary novelty of the regulatory mechanism underlying stem growth in soybean. PMID- 26807728 TI - Microbial Community Profiles in Wastewaters from Onsite Wastewater Treatment Systems Technology. AB - The aim of the study was to determine the potential of community-level physiological profiles (CLPPs) methodology as an assay for characterization of the metabolic diversity of wastewater samples and to link the metabolic diversity patterns to efficiency of select onsite biological wastewater facilities. Metabolic fingerprints obtained from the selected samples were used to understand functional diversity implied by the carbon substrate shifts. Three different biological facilities of onsite wastewater treatment were evaluated: fixed bed reactor (technology A), trickling filter/biofilter system (technology B), and aerated filter system (the fluidized bed reactor, technology C). High similarities of the microbial community functional structures were found among the samples from the three onsite wastewater treatment plants (WWTPs), as shown by the diversity indices. Principal components analysis (PCA) showed that the diversity and CLPPs of microbial communities depended on the working efficiency of the wastewater treatment technologies. This study provided an overall picture of microbial community functional structures of investigated samples in WWTPs and discerned the linkages between microbial communities and technologies of onsite WWTPs used. The results obtained confirmed that metabolic profiles could be used to monitor treatment processes as valuable biological indicators of onsite wastewater treatment technologies efficiency. This is the first step toward understanding relations of technology types with microbial community patterns in raw and treated wastewaters. PMID- 26807729 TI - Correction: A Kinetic and Factorial Approach to Study the Effects of Temperature and Salinity on Growth and Toxin Production by the Dinoflagellate Alexandrium ostenfeldii from the Baltic Sea. PMID- 26807730 TI - Characterization of Heterogeneous Prostate Tumors in Targeted Pten Knockout Mice. AB - Previously, we generated a preclinical mouse prostate tumor model based on PSA Cre driven inactivation of Pten. In this model homogeneous hyperplastic prostates (4-5m) developed at older age (>10m) into tumors. Here, we describe the molecular and histological characterization of the tumors in order to better understand the processes that are associated with prostate tumorigenesis in this targeted mouse Pten knockout model. The morphologies of the tumors that developed were very heterogeneous. Different histopathological growth patterns could be identified, including intraductal carcinoma (IDC), adenocarcinoma and undifferentiated carcinoma, all strongly positive for the epithelial cell marker Cytokeratin (CK), and carcinosarcomas, which were negative for CK. IDC pattern was already detected in prostates of 7-8 month old mice, indicating that it could be a precursor stage. At more than 10 months IDC and carcinosarcoma were most frequently observed. Gene expression profiling discriminated essentially two molecular subtypes, denoted tumor class 1 (TC1) and tumor class 2 (TC2). TC1 tumors were characterized by high expression of epithelial markers like Cytokeratin 8 and E Cadherin whereas TC2 tumors showed high expression of mesenchyme/stroma markers such as Snail and Fibronectin. These molecular subtypes corresponded with histological growth patterns: where TC1 tumors mainly represented adenocarcinoma/intraductal carcinoma, in TC2 tumors carcinosarcoma was the dominant growth pattern. Further molecular characterization of the prostate tumors revealed an increased expression of genes associated with the inflammatory response. Moreover, functional markers for senescence, proliferation, angiogenesis and apoptosis were higher expressed in tumors compared to hyperplasia. The highest expression of proliferation and angiogenesis markers was detected in TC2 tumors. Our data clearly showed that in the genetically well defined PSA-Cre;Pten-loxP/loxP prostate tumor model, histopathological, molecular and biological heterogeneity occurred during later stages of tumor development. PMID- 26807731 TI - Amyloid deposition in semantic dementia: a positron emission tomography study. AB - BACKGROUND: Pittsburgh compound B ([11C]-PIB) identifies amyloid-beta (Abeta) deposition in vivo. Asymptomatic Abeta deposition has been reported consistently in some healthy older subjects. Of patients with frontotemporal dementia, those who have later onset have a higher potential for Abeta deposition. OBJECTIVE: Comparison of Abeta deposition in Alzheimer's disease (AD), healthy older controls, and patients with early- and late-onset semantic dementia (SD), a subtype of frontotemporal dementia. METHODS: Subjects were recruited from tertiary academic care centers specializing in assessment and management of patients with neurodegenerative disease. We used the radiotracer [11C]-PIB in a high-resolution positron emission tomography scanner to evaluate 11 participants with SD (six with onset before age 65 and five with later onset), 9 with probable AD, and 10 controls over age 60. The main outcome measures were frontal, temporal, parietal, and total [11C]-PIB standardized uptake value ratios to establish PIB-positive (PIB+) cutoff. RESULTS: The five patients with late-onset SD were PIB-negative. Two of six with early-onset SD, seven of nine with AD, and 1 of 10 controls were PIB+. The SD participants who were PIB+ did not have memory or visuospatial deficits that are typical in AD. CONCLUSIONS: Abeta deposition does not seem to be associated with late-onset SD. Future larger studies might confirm whether a significant minority of early-onset SD patients exhibit Abeta deposition. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26807732 TI - A Rare Glimpse of Paleoarchean Life: Geobiology of an Exceptionally Preserved Microbial Mat Facies from the 3.4 Ga Strelley Pool Formation, Western Australia. AB - Paleoarchean rocks from the Pilbara Craton of Western Australia provide a variety of clues to the existence of early life on Earth, such as stromatolites, putative microfossils and geochemical signatures of microbial activity. However, some of these features have also been explained by non-biological processes. Further lines of evidence are therefore required to convincingly argue for the presence of microbial life. Here we describe a new type of microbial mat facies from the 3.4 Ga Strelley Pool Formation, which directly overlies well known stromatolitic carbonates from the same formation. This microbial mat facies consists of laminated, very fine-grained black cherts with discontinuous white quartz layers and lenses, and contains small domical stromatolites and wind-blown crescentic ripples. Light- and cathodoluminescence microscopy, Raman spectroscopy, and time of flight-secondary ion mass spectrometry (ToF-SIMS) reveal a spatial association of carbonates, organic material, and highly abundant framboidal pyrite within the black cherts. Nano secondary ion mass spectrometry (NanoSIMS) confirmed the presence of distinct spheroidal carbonate bodies up to several tens of MUm that are surrounded by organic material and pyrite. These aggregates are interpreted as biogenic. Comparison with Phanerozoic analogues indicates that the facies represents microbial mats formed in a shallow marine environment. Carbonate precipitation and silicification by hydrothermal fluids occurred during sedimentation and earliest diagenesis. The deciphered environment, as well as the delta13C signature of bulk organic matter (-35.30/00), are in accord with the presence of photoautotrophs. At the same time, highly abundant framboidal pyrite exhibits a sulfur isotopic signature (delta34S = +3.050/00; Delta33S = 0.2680/00; and Delta36S = -0.2820/00) that is consistent with microbial sulfate reduction. Taken together, our results strongly support a microbial mat origin of the black chert facies, thus providing another line of evidence for life in the 3.4 Ga Strelley Pool Formation. PMID- 26807733 TI - Mitochondrial Protein PGAM5 Regulates Mitophagic Protection against Cell Necroptosis. AB - Necroptosis as a molecular program, rather than simply incidental cell death, was established by elucidating the roles of receptor interacting protein (RIP) kinases 1 and 3, along with their downstream partner, mixed lineage kinase-like domain protein (MLKL). Previous studies suggested that phosphoglycerate mutase family member 5 (PGAM5), a mitochondrial protein that associates with RIP1/RIP3/MLKL complex, promotes necroptosis. We have generated mice deficient in the pgam5 gene and surprisingly found PGAM5-deficiency exacerbated rather than reduced necroptosis in response to multiple in vitro and in vivo necroptotic stimuli, including ischemic reperfusion injury (I/R) in the heart and brain. Electron microscopy, biochemical, and confocal analysis revealed that PGAM5 is indispensable for the process of PINK1 dependent mitophagy which antagonizes necroptosis. The loss of PGAM5/PINK1 mediated mitophagy causes the accumulation of abnormal mitochondria, leading to the overproduction of reactive oxygen species (ROS) that worsen necroptosis. Our results revise the former proposal that PGAM5 acts downstream of RIP1/RIP3 to mediate necroptosis. Instead, PGAM5 protects cells from necroptosis by independently promoting mitophagy. PGAM5 promotion of mitophagy may represent a therapeutic target for stroke, myocardial infarction and other diseases caused by oxidative damage and necroptosis. PMID- 26807735 TI - Microbial production of mammalian melatonin - a promising solution to melatonin industry. PMID- 26807734 TI - Surveillance for Western Equine Encephalitis, St. Louis Encephalitis, and West Nile Viruses Using Reverse Transcription Loop-Mediated Isothermal Amplification. AB - Collection of mosquitoes and testing for vector-borne viruses is a key surveillance activity that directly influences the vector control efforts of public health agencies, including determining when and where to apply insecticides. Vector control districts in California routinely monitor for three human pathogenic viruses including West Nile virus (WNV), Western equine encephalitis virus (WEEV), and St. Louis encephalitis virus (SLEV). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) offers highly sensitive and specific detection of these three viruses in a single multiplex reaction, but this technique requires costly, specialized equipment that is generally only available in centralized public health laboratories. We report the use of reverse transcription loop-mediated isothermal amplification (RT-LAMP) to detect WNV, WEEV, and SLEV RNA extracted from pooled mosquito samples collected in California, including novel primer sets for specific detection of WEEV and SLEV, targeting the nonstructural protein 4 (nsP4) gene of WEEV and the 3' untranslated region (3'-UTR) of SLEV. Our WEEV and SLEV RT-LAMP primers allowed detection of <0.1 PFU/reaction of their respective targets in <30 minutes, and exhibited high specificity without cross reactivity when tested against a panel of alphaviruses and flaviviruses. Furthermore, the SLEV primers do not cross react with WNV, despite both viruses being closely related members of the Japanese encephalitis virus complex. The SLEV and WEEV primers can also be combined in a single RT-LAMP reaction, with discrimination between amplicons by melt curve analysis. Although RT-qPCR is approximately one order of magnitude more sensitive than RT-LAMP for all three targets, the RT-LAMP technique is less instrumentally intensive than RT-qPCR and provides a more cost-effective method of vector-borne virus surveillance. PMID- 26807736 TI - Clear Cell Adenocarcinoma of the Female Urethra: Four Case Presentations of a Clinical and Pathological Entity Requiring Radical Surgery. AB - Clear cell adenocarcinoma of the female urethra is a rare tumour of unknown origin. Here, we report 4 patients with such malignancy and argue for proper identification of the disease entity and radical surgery based on the available literature. PMID- 26807737 TI - The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long Term Kidney Function in Wistar Rats. AB - BACKGROUND: Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation (EUGR) could be a modulator. METHODS: Wistar rats were cross-fostered in normal food or food restricted litters at postnatal day (PND) 2 and treated daily with 0.9% NaCl, 5 mg/kg furosemide or 5 mg/kg hydrochlorothiazide (HCTZ) up to PND 8. Kidneys were evaluated on proliferation, apoptosis and a set of mRNA target genes at PND 8, glomerular- and glomerular generation count at PND 35, clinical pathology parameters at 3- and 9 months, neutrophil gelatinase-associated lipocalin at PND 8, 3 and 6 months, monthly blood pressure from 3 months onward and histopathology at study end. RESULTS: Treatment with furosemide or HCTZ did not have relevant effects on measured parameters. EUGR resulted in lower body weight from day 3 onwards (-29% at weaning; p < 0.001, -10% at necropsy; p < 0.001), less glomerular generations (4.4 +/- 0.32 vs. 5.0 +/- 0.423; p = 0.025, males only), decreased glomerular numbers (27,861 +/- 3,468 vs. 30,527 +/- 4,096; p = 0.026), higher creatinine clearance (0.84 +/- 0.1 vs. 0.77 +/- 0.09 ml/min/kg; p = 0.047) at 3 months and lower plasma creatinine (25.7 +/- 1.8 vs. 27.5 +/- 2.8 umol/l; p = 0.043) at 9 months. CONCLUSION: Furosemide and HCTZ did not influence kidney development or function when administered in a clinically relevant dose to rat pups at a stage of ongoing nephrogenesis. EUGR led to impaired kidney development but did not modify furosemide or HCTZ findings. PMID- 26807738 TI - Individual FEV1 Trajectories Can Be Identified from a COPD Cohort. AB - OBJECTIVE: We aim to make use of clinical spirometry data in order to identify individual COPD-patients with divergent trajectories of lung function over time. STUDY DESIGN AND SETTING: Hospital-based COPD cohort (N = 607) was followed on average 4.6 years. Each patient had a mean of 8.4 spirometries available. We used a Hierarchical Bayesian Model (HBM) to identify the individuals presenting constant trends in lung function. RESULTS: At a probability level of 95%, one third of the patients (180/607) presented rapidly declining FEV1 (mean -78 ml/year, 95% CI -73 to -83 ml) compared to that in the rest of the patients (mean -26 ml/year, 95% CI -23 to -29 ml, p <= 2.2 * 10(-16)). Constant improvement of FEV1 was very rare. The rapid decliners more frequently suffered from exacerbations measured by various outcome markers. CONCLUSION: Clinical data of unique patients can be utilized to identify diverging trajectories of FEV1 with a high probability. Frequent exacerbations were more prevalent in FEV1-decliners than in the rest of the patients. The result confirmed previously reported association between FEV1 decline and exacerbation rate and further suggested that in clinical practice HBM could improve the identification of high-risk individuals at early stages of the disease. PMID- 26807739 TI - Peritoneal dialysis practice in Australia and New Zealand: A call to sustain the action. AB - This paper updates a previous 'Call to Action' paper (Nephrology 2011; 16: 19-29) that reviewed key outcome data for Australian and New Zealand peritoneal dialysis patients and made recommendations to improve care. Since its publication, peritonitis rates have improved significantly, although they have plateaued more recently. Peritoneal dialysis patient and technique survival in Australian and New Zealand have also improved, with a reduction in the proportion of technique failures attributed to 'social reasons'. Despite these improvements, technique survival rates overall remain lower than in many other parts of the world. This update includes additional practical recommendations based on published evidence and emerging initiatives to further improve outcomes. PMID- 26807740 TI - Does Radiotherapy for the Primary Tumor Benefit Prostate Cancer Patients with Distant Metastasis at Initial Diagnosis? AB - PURPOSE/OBJECTIVES: Treatment of the primary tumor reportedly improves survival in several types of metastatic cancer. We herein evaluated the efficacy and toxicity of radiotherapy for the primary tumor in prostate cancer with metastasis. MATERIALS/METHODS: The study cohort included 140 men with metastatic prostate cancer at initial diagnosis. Metastatic sites were divided into 4 groups as follows: solitary bone, 2-4 bones, >=5 bones, and visceral organs. Patient, tumor, and treatment characteristics, and clinical outcomes were compared between patients treated with (prostate radiotherapy [PRT] group) or without radiotherapy to the primary tumor. RESULTS: Patients in PRT group presented with a statistically significantly younger age (p = .02), whereas other characteristics showed no significant difference. Overall survival (OS) and biochemical failure free survival (BCFFS) were improved in PRT patients (3-year OS: 69% vs. 43%, p = 0.004; 3-year BCFFS: 52% vs. 16%, p = 0.002). Multivariate analysis identified PRT as a significant predictor of both OS (hazard ratio [HR] = 0.43, p = 0.015). None of the 38 PRT patients experienced severe (grade >=3) genitourinary or gastrointestinal toxicity. CONCLUSIONS: Our data suggest that radiotherapy to the primary tumor was associated with improved OS and BCFFS in metastatic prostate cancer. The results of this study warrant prospective controlled clinical trials of this approach in stage IV prostate cancer patients with limited extent of bone metastasis and good performance status. PMID- 26807741 TI - Correction: Dimethyl Fumarate Ameliorates Lewis Rat Experimental Autoimmune Neuritis and Mediates Axonal Protection. PMID- 26807742 TI - Endovascular Treatment with Stent-Retriever Devices for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials. AB - IMPORTANCE: Acute ischemic stroke is a leading cause of death and disability worldwide. Several recent clinical trials have shown that endovascular treatment improves clinical outcomes among patients with acute ischemic stroke. OBJECTIVE: To provide an overall and precise estimate of the efficacy of endovascular treatment predominantly using second-generation mechanical thrombectomy devices (stent-retriever devices) compared to medical management on clinical and functional outcomes among patients with acute ischemic stroke. DATA SOURCES: MEDLINE, EMBASE, Cochrane Collaboration Central Register of Controlled Clinical Trials, Web of Science, and NIH ClinicalTrials.gov were searched through November 2015. STUDY SELECTION: Searches returned 3,045 articles. After removal of duplicates, two authors independently screened titles and abstracts to assess eligibility of 2,495 potentially relevant publications. From these, 38 full-text publications were more closely assessed. Finally, 5 randomized controlled trials of endovascular treatment with predominant use of retrievable stents were selected. DATA EXTRACTION AND SYNTHESIS: Three authors independently extracted information on participant and trial characteristics and clinical events using a standardized protocol. Random effects models were used to pool endovascular treatment effects across outcomes. MAIN OUTCOMES AND MEASURES: The primary outcome was better functional outcome as measured on the modified Rankin Scale at 90 days of follow-up. Secondary outcomes included all-cause mortality and symptomatic intra-cerebral hemorrhage. RESULTS: Five trials representing 1,287 patients were included. Overall, patients randomized to endovascular therapy experienced 2.22 times greater odds of better functional outcome compared to those randomized to medical management (95% CI, 1.66 to 2.98; P < 0.0001). Endovascular therapy was not associated with mortality [OR (95% CI), 0.78 (0.54, 1.12); P = 0.1056] or symptomatic intracerebral hemorrhage [OR (95% CI), 1.19 (0.69, 2.05); P = 0.5348]. Meta-regression analysis suggested that shorter times from stroke onset to groin puncture and from stroke onset to reperfusion result in better functional outcomes in ischemic stroke patients (P = 0.0077 and P = 0.0089). There were no significant differences in the beneficial effects of endovascular treatment on functional outcomes across categories of gender, age, stroke severity, ischemic changes on computed tomography, or intravenous tissue plasminogen activator administration. CONCLUSIONS AND RELEVANCE: This meta analysis demonstrated superior functional outcomes in subjects receiving endovascular treatment compared to medical management. Further, this analysis showed that acute ischemic stroke patients may receive enhanced functional benefit from earlier endovascular treatment. PMID- 26807743 TI - Erinacine S, a Rare Sesterterpene from the Mycelia of Hericium erinaceus. AB - A new sesterterpene, erinacine S, and one cyathane diterpene xyloside, erinacine A, were isolated from the ethanol extract of the mycelia of Hericium erinaceus. Their structures were elucidated by spectroscopic and X-ray analysis. A 30-day oral course of erinacines A and S attenuated Abeta plaque burden in the brains of 5-month-old female APP/PS1 transgenic mice. Moreover, erinacines A and S significantly increased the level of insulin-degrading enzyme in cerebral cortex. PMID- 26807744 TI - How Resource Phenology Affects Consumer Population Dynamics. AB - Climate change drives uneven phenology shifts across taxa, and this can result in changes to the phenological match between interacting species. Shifts in the relative phenology of partner species are well documented, but few studies have addressed the effects of such changes on population dynamics. To explore this, we develop a phenologically explicit model describing consumer-resource interactions. Focusing on scenarios for univoltine insects, we show how changes in resource phenology can be reinterpreted as transformations in the year-to-year recursion relationships defining consumer population dynamics. This perspective provides a straightforward path for interpreting the long-term population consequences of phenology change. Specifically, by relating the outcome of phenological shifts to species traits governing recursion relationships (e.g., consumer fecundity or competitive scenario), we demonstrate how changes in relative phenology can force systems into different dynamical regimes, with major implications for resource management, conservation, and other areas of applied dynamics. PMID- 26807745 TI - The Effects of Plant Compensatory Regrowth and Induced Resistance on Herbivore Population Dynamics. AB - Outbreaks of herbivorous insects are detrimental to natural and agricultural systems, but the mechanisms driving outbreaks are not well understood. Plant responses to herbivory have the potential to produce outbreaks, but long-term effects of plant responses on herbivore dynamics are understudied. To quantify these effects, we analyze mathematical models of univoltine herbivores consuming annual plants with two responses: (1) compensatory regrowth, which affects herbivore survival in food-limited situations by increasing the amount of food available to the herbivore; and (2) induced resistance, which reduces herbivore survival proportional to the strength of the response. Compensatory regrowth includes tolerance, where plants replace some or all of the consumed biomass, and overcompensation, where plants produce more biomass than was consumed. We found that overcompensation can cause bounded fluctuations in the herbivore density (called outbreaks here) by itself, whereas neither tolerance nor induced resistance can cause an outbreak on its own. Food limitation and induced resistance can also drive outbreaks when they act simultaneously. Tolerance damps these outbreaks, but overcompensation, by contrast, qualitatively changes the conditions under which the outbreaks occur. Not properly accounting for these interactions may explain why it has been difficult to document plant-driven insect outbreaks and could undermine efforts to control herbivore populations in agricultural systems. PMID- 26807746 TI - Artificial Selection Reveals High Genetic Variation in Phenology at the Trailing Edge of a Species Range. AB - Species responses to climate change depend on the interplay of migration and adaptation, yet we know relatively little about the potential for adaptation. Genetic adaptations to climate change often involve shifts in the timing of phenological events, such as flowering. If populations at the edge of a species range have lower genetic variation in phenological traits than central populations, then their persistence under climate change could be threatened. To test this hypothesis, we performed artificial selection experiments using the scarlet monkeyflower (Mimulus cardinalis) and compared genetic variation in flowering time among populations at the latitudinal center, northern edge, and southern edge of the species range. We also assessed whether selection on flowering time yielded correlated responses in functional traits, potentially representing a cost associated with early or late flowering. Contrary to prediction, southern populations exhibited greater responses to selection on flowering time than central or northern populations. Further, selection for early flowering resulted in correlated increases in specific leaf area and leaf nitrogen, whereas selection for late flowering led to decreases in these traits. These results provide critical insights about how spatial variation in the potential for adaptation may affect population persistence under changing climates. PMID- 26807747 TI - Inaccurate Color Discrimination by Pollinators Promotes Evolution of Discrete Color Polymorphism in Food-Deceptive Flowers. AB - Many plant species employing a food-deceptive pollination strategy show discrete or continuous floral polymorphism within their populations. Previous studies have suggested that negative frequency-dependent selection (NFDS) caused by the learning behavior of pollinators was responsible for the maintenance of floral polymorphism. However, NFDS alone does not explain why and when discrete or continuous polymorphism evolves. In this study, we use an evolutionary simulation model to propose that inaccurate discrimination of flower colors by pollinators results in evolution of discrete flower color polymorphism. Simulations showed that associative learning based on inaccurate discrimination in pollinators caused disruptive selection of flower colors. The degree of inaccuracy determined the number of discrete flower colors that evolved. Our results suggest that animal behavior based on inaccurate discrimination may be a general cause of disruptive selection that promotes discrete trait polymorphism. PMID- 26807748 TI - Mimetic Divergence and the Speciation Continuum in the Mimic Poison Frog Ranitomeya imitator. AB - While divergent ecological adaptation can drive speciation, understanding the factors that facilitate or constrain this process remains a major goal in speciation research. Here, we study two mimetic transition zones in the poison frog Ranitomeya imitator, a species that has undergone a Mullerian mimetic radiation to establish four morphs in Peru. We find that mimetic morphs are strongly phenotypically differentiated, producing geographic clines with varying widths. However, distinct morphs show little neutral genetic divergence, and landscape genetic analyses implicate isolation by distance as the primary determinant of among-population genetic differentiation. Mate choice experiments suggest random mating at the transition zones, although certain allopatric populations show a preference for their own morph. We present evidence that this preference may be mediated by color pattern specifically. These results contrast with an earlier study of a third transition zone, in which a mimetic shift was associated with reproductive isolation. Overall, our results suggest that the three known mimetic transition zones in R. imitator reflect a speciation continuum, which we have characterized at the geographic, phenotypic, behavioral, and genetic levels. We discuss possible explanations for variable progress toward speciation, suggesting that multifarious selection on both mimetic color pattern and body size may be responsible for generating reproductive isolation. PMID- 26807749 TI - Aggregation of Infective Stages of Parasites as an Adaptation and Its Implications for the Study of Parasite-Host Interactions. AB - The causes and consequences of aggregation among conspecifics have received much attention. For infecting macroparasites, causes include variation among hosts in susceptibility and whether infective stages are aggregated in the environment. Here, we link these two phenomena and explore whether aggregation of infective stages in the environment is adaptive to parasites encountering host condition linked defenses and what effect such aggregations have for parasite-host interactions. Using simulation models, we show that parasite fitness is increased by aggregates attacking a host, particularly when investment into defenses is high. The fitness benefit of aggregation remains despite inclusion of factors that should curb the benefits of aggregation, namely, mortality of low-condition hosts (those hosts expected to be most susceptible to parasitism) and costs of high coinfection. For sample sizes common in studies, aggregation of infective stages reduces the likelihood of detecting host condition-parasitism relations, even when host condition is the only other factor in models affecting parasitism. Thus, it is not surprising that the expected inverse relations between host condition and parasitism, commonly a premise in studies of parasite-host interactions, are inconsistently found. An understanding of how parasites encounter hosts is thus needed for developing theory for parasite-host ecological and evolutionary interactions. PMID- 26807750 TI - The Effect of Immigration on the Adaptation of Microbial Communities to Warming. AB - Theory predicts that immigration can either enhance or impair the rate at which species and whole communities adapt to environmental change, depending on the traits of genotypes and species in the source pool relative to local conditions. These responses, in turn, will determine how well whole communities function in changing environments. We tested the effects of immigration and experimental warming on microbial communities during an 81-day field experiment. The effects of immigration depended on the warming treatment. In warmed communities, immigration was detrimental to community growth, whereas in ambient communities it was beneficial. This result is explained by colonists coming from a local species pool preadapted to ambient conditions. Loss of metabolic diversity, however, was buffered by immigration in both environments. Communities showed increasing local adaptation to temperature conditions during the experiment, and this was independent of whether they received immigration. Genotypes that comprised the communities were not locally adapted, however, indicating that community local adaptation can be independent of adaptation of component genotypes. Our results are consistent with a greater role for species interactions rather than adaptation of constituent species in determining local adaptation of whole communities and confirm that immigration can either enhance or impair community responses to environmental change depending on the environmental context. PMID- 26807751 TI - Hybrid Incompatibilities, Local Adaptation, and the Genomic Distribution of Natural Introgression between Species. AB - Under allopatric speciation, geographic barriers eliminate gene flow between eventual species at all loci in the genome simultaneously. There is increasing evidence, however, that speciation can be complex, with some loci experiencing gene flow during speciation or during bouts of secondary contact. In taxa with heteromorphic sex chromosomes-birds, butterflies, mammals, and Drosophila-the X (or Z) chromosome generally shows reduced levels of gene flow compared to autosomes. To investigate why, we develop population genetic models of secondary contact and gene flow at a neutral locus that is genetically linked to selected loci involved in hybrid incompatibilities and/or local adaptation. Using models that assume weak migration and strong selection, we compare gene flow at X-linked versus autosomal neutral loci as a function of linkage, dominance, sex-specific selection, and sex-specific recombination. For most cases, gene flow at neutral loci on the X is reduced relative to autosomes, as the greater efficacy of hemizygous selection in XY hybrids reduces the opportunity for neutral migrant alleles to escape their genetically linked, locally disfavored alleles via recombination. There are some circumstances, however, involving sex-limited selection and sex-limited recombination that allow neutral loci on the X to introgress more readily than those on autosomes. PMID- 26807752 TI - Hidden in Plain Sight: How Ventral Line Markings in Chameleons May Enhance Camouflage. AB - Chameleons, lizards often synonymous with camouflage for their color-changing abilities, possess a variety of permanent coloration patterns whose evolutionary significance remains largely unknown. In this study, we explore the potential for white ventral line markings in species across the genus Chamaeleonidae to function as a camouflage pattern against diurnal predators. Diurnal behavioral field studies of the white-lined chameleon Furcifer viridis showed that individuals typically exposed ventral line markings during the characteristic ring-flip antipredator behavior in response to a predatory threat. These ventral line markings are largely inconspicuous in other postures. Comparative morphological analyses of 86 species found that there was a significant positive correlation between ventral line markings with arboreal habitat type, even when accounting for phylogeny. These results suggest that ventral line markings (and the ring-flip behavior) could act as a disruptive or mimetic coloration marking for arboreal chameleons against visual diurnal predators. Further work testing differential predation rates is necessary in order to verify the proposed function of these line markings. PMID- 26807753 TI - Out-Group Threat Promotes Within-Group Affiliation in a Cooperative Fish. AB - In social species, conflict with outsiders is predicted to affect within-group interactions and thus influence group dynamics and the evolution and maintenance of sociality. Although empirical evidence exists for a relationship between out group conflict and intragroup behavior in humans, experimental tests in other animals are rare. In a model fish system, we show that simulated out-group intrusions cause postconflict increases in intragroup affiliation but no changes in postconflict intragroup aggression. Postconflict affiliation was greater following intrusions by neighboring compared with nonneighboring individuals; neighbors represent greater threats to the dominance rank and breeding success of residents, and they are visible in the aftermath of the intrusion. By providing strong evidence of a link between out-group conflict and postconflict intragroup behavior and demonstrating that intragroup affiliation is affected by the nature of the out-group intrusion, our study shows the importance of considering postconflict behavior for our understanding of cooperation and social structure. PMID- 26807754 TI - Energetic Constraints on Fungal Growth. AB - Saprotrophic fungi are obliged to spend energy on growth, reproduction, and substrate digestion. To understand the trade-offs involved, we developed a model that, for any given growth rate, identifies the strategy that maximizes the fraction of energy that could possibly be spent on reproduction. Our model's predictions of growth rates and bioconversion efficiencies are consistent with empirical findings, and it predicts the optimal investment in reproduction, resource acquisition, and biomass recycling for a given environment and timescale of reproduction. Thus, if the timescale of reproduction is long compared to the time required for the fungus to double in size, the model suggests that the total energy available for reproduction is maximal when a very small fraction of the energy budget is spent on reproduction. The model also suggests that fungi growing on substrates with a high concentration of low-molecular-weight compounds will not benefit from recycling: they should be able to grow more rapidly and allocate more energy to reproduction without recycling. In contrast, recycling offers considerable benefits to fungi growing on recalcitrant substrates, where the individual hyphae are not crowded and the time taken to consume resource is significantly longer than the fungus doubling time. PMID- 26807755 TI - Quantifying Global Drivers of Zoonotic Bat Viruses: A Process-Based Perspective. AB - Emerging infectious diseases (EIDs), particularly zoonoses, represent a significant threat to global health. Emergence is often driven by anthropogenic activity (e.g., travel, land use change). Although disease emergence frameworks suggest multiple steps from initial zoonotic transmission to human-to-human spread, there have been few attempts to empirically model specific steps. We create a process-based framework to separate out components of individual emergence steps. We focus on early emergence and expand the first step, zoonotic transmission, into processes of generation of pathogen richness, transmission opportunity, and establishment, each with its own hypothesized drivers. Using this structure, we build a spatial empirical model of these drivers, taking bat viruses shared with humans as a case study. We show that drivers of both viral richness (host diversity and climatic variability) and transmission opportunity (human population density, bushmeat hunting, and livestock production) are associated with virus sharing between humans and bats. We also show spatial heterogeneity between the global patterns of these two processes, suggesting that high-priority locations for pathogen discovery and surveillance in wildlife may not necessarily coincide with those for public health intervention. Finally, we offer direction for future studies of zoonotic EIDs by highlighting the importance of the processes underlying their emergence. PMID- 26807756 TI - New frontiers in fibrotic disease therapies: The focus of the Joan and Joel Rosenbloom Center for Fibrotic Diseases at Thomas Jefferson University. AB - Fibrotic diseases constitute a world-wide major health problem, but research support remains inadequate in comparison to the need. Although considerable understanding of the pathogenesis of fibrotic reactions has been attained, no completely effective therapies exist. Although fibrotic disorders are diverse, it is universally appreciated that a particular cell type with unique characteristics, the myofibroblast, is responsible for replacement of functioning tissue with non-functional scar tissue. Understanding the cellular and molecular mechanisms responsible for the creation of myofibroblasts and their activities is central to the development of therapies. Critical signaling cascades, initiated primarily by TGF-beta, but also involving other cytokines which stimulate pro fibrotic reactions in the myofibroblast, offer potential therapeutic targets. However, because of the multiplicity and complex interactions of these signaling pathways, it is very unlikely that any single drug will be successful in modifying a major fibrotic disease. Therefore, we have chosen to examine the effectiveness of administration of several drug combinations in a mouse pneumoconiosis model. Such treatment proved to be effective. Because fibrotic diseases that tend to be chronic, are difficult to monitor, and are patient variable, implementation of clinical trials is difficult and expensive. Therefore, we have made efforts to identify and validate non-invasive biomarkers found in urine and blood. We describe the potential utility of five such markers: (i) the EDA form of fibronectin (Fn(EDA)), (ii) lysyl oxidase (LOX), (iii) lysyl oxidase-like protein 2 (LoxL2), (iv) connective tissue growth factor (CTGF, CCNII), and (v) the N-terminal propeptide of type III procollagen (PIIINP). PMID- 26807757 TI - The cartilage extracellular matrix as a transient developmental scaffold for growth plate maturation. AB - The cartilage growth plate is a specialized developmental tissue containing characteristic zonal arrangements of chondrocytes. The proliferative and differentiative states of chondrocytes are tightly regulated at all stages including the initial limb bud and rudiment cartilage stages of development, the establishment of the primary and secondary ossification centers, development of the growth plates and laying down of bone. A multitude of spatio-temporal signals, including transcription factors, growth factors, morphogens and hormones, control chondrocyte maturation and terminal chondrocyte differentiation/hypertrophy, cell death/differentiation, calcification and vascular invasion of the growth plate and bone formation during morphogenetic transition of the growth plate. This involves hierarchical, integrated signaling from growth and factors, transcription factors, mechanosensory cues and proteases in the extracellular matrix to regulate these developmental processes to facilitate progressive changes in the growth plate culminating in bone formation and endochondral ossification. This review provides an overview of selected components which have particularly important roles in growth plate biology including collagens, proteoglycans, glycosaminoglycans, growth factors, proteases and enzymes. PMID- 26807758 TI - Inflammation, fibrosis, and modulation of the process by mesenchymal stem/stromal cells. AB - Fibrosis and scarring are the end stage of many disease processes. In effect, the collagen fibers that initially provide a necessary strength during the repair of injured tissues are frequently synthesized in excessive amounts and become irreversible fibrotic deposits that limit regeneration of the endogenous cells of a tissue. This review will focus on the potential of mesenchymal stem/stromal cells for treatment of fibrotic diseases, with emphasis on the role of TSG-6 as a mediator of anti-inflammatory effects. PMID- 26807759 TI - Intrinsically disordered proteins and biomineralization. AB - In vertebrates and invertebrates, biomineralization is controlled by the cell and the proteins they produce. A large number of these proteins are intrinsically disordered, gaining some secondary structure when they interact with their binding partners. These partners include the component ions of the mineral being deposited, the crystals themselves, the template on which the initial crystals form, and other intrinsically disordered proteins and peptides. This review speculates why intrinsically disordered proteins are so important for biomineralization, providing illustrations from the SIBLING (small integrin binding N-glycosylated) proteins and their peptides. It is concluded that the flexible structure, and the ability of the intrinsically disordered proteins to bind to a multitude of surfaces is crucial, but details on the precise interactions, energetics and kinetics of binding remain to be determined. PMID- 26807760 TI - Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of Systemic Sclerosis-associated pulmonary fibrosis and pulmonary arterial hypertension. Myth or reality? AB - Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and multiple internal organs and severe functional and structural microvascular alterations. SSc is considered to be the prototypic systemic fibrotic disorder. Despite currently available therapeutic approaches SSc has a high mortality rate owing to the development of SSc-associated interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), complications that have emerged as the most frequent causes of disability and mortality in SSc. The pathogenesis of the fibrotic process in SSc is complex and despite extensive investigation the exact mechanisms have remained elusive. Myofibroblasts are the cells ultimately responsible for tissue fibrosis and fibroproliferative vasculopathy in SSc. Tissue myofibroblasts in SSc originate from several sources including expansion of quiescent tissue fibroblasts and tissue accumulation of CD34+ fibrocytes. Besides these sources, myofibroblasts in SSc may result from the phenotypic conversion of endothelial cells into activated myofibroblasts, a process known as endothelial to mesenchymal transition (EndoMT). Recently, it has been postulated that EndoMT may play a role in the development of SSc-associated ILD and PAH. However, although several studies have described the occurrence of EndoMT in experimentally induced cardiac, renal, and pulmonary fibrosis and in several human disorders, the contribution of EndoMT to SSc-associated ILD and PAH has not been generally accepted. Here, the experimental evidence supporting the concept that EndoMT plays a role in the pathogenesis of SSc-associated ILD and PAH will be reviewed. PMID- 26807762 TI - Introduction to mini-review cluster on fibrotic diseases: A Festschrift to Joel Rosenbloom, M.D., Ph.D. PMID- 26807763 TI - TGF-beta signalling and liver disease. AB - The transforming growth factor-beta (TGF-beta) family signalling pathways play essential roles in the regulation of different cellular processes, including proliferation, differentiation, migration or cell death, which are essential for the homeostasis of tissues and organs. Because of the diverse and pleiotropic TGF beta functions, deregulation of its pathways contributes to human disease. In the case of the liver, TGF-beta signalling participates in all stages of disease progression, from initial liver injury through inflammation and fibrosis, to cirrhosis and cancer. TGF-beta has cytostatic and apoptotic effects in hepatocytes, promoting liver differentiation during embryogenesis and physiological liver regeneration. However, high levels of TGF-beta, as a consequence of chronic liver damage, result in activation of stellate cells to myofibroblasts and massive hepatocyte cell death, which contributes to the promotion of liver fibrosis and later cirrhosis. During liver tumorigenesis, TGF beta may behave as a suppressor factor at early stages; however, there is strong evidence that overactivation of TGF-beta signalling might contribute to later tumour progression, once cells escape from its cytostatic effects. For these reasons, targeting the TGF-beta signalling pathway is being explored to counteract liver disease progression. In this review, we aim to shed light on the state-of-the-art in the signalling pathways induced by TGF-beta that are involved in different stages of liver physiology and pathology. PMID- 26807761 TI - Matricellular proteins as regulators of cancer metastasis to bone. AB - Metastasis is the major cause of death in cancer patients, and a frequent site of metastasis for many cancers is the bone marrow. Therefore, understanding the mechanisms underlying the metastatic process is necessary for future prevention and treatment. The tumor microenvironment is now known to play a role in the metastatic cascade, both at the primary tumor and in metastatic sites, and includes both cellular and non-cellular components. The extracellular matrix (ECM) provides structural support and signaling cues to cells. One particular group of molecules associated with the ECM, known as matricellular proteins, modulate multiple aspects of tumor biology, including growth, migration, invasion, angiogenesis and metastasis. These proteins are also important for normal function in the bone by regulating bone formation and bone resorption. Recent studies have described a link between some of these proteins and metastasis of various tumors to the bone. The aim of this review is to summarize what is currently known about matricellular protein influence on bone metastasis. Particular attention to the contribution of both tumor cells and non-malignant cells in the bone has been given. PMID- 26807764 TI - Anticancer activity of synthetic bis(indolyl)methane-ortho-biaryls against human cervical cancer (HeLa) cells. AB - Bis(indolyl)methane appended biaryls were designed, synthesized and evaluated in human cervical cancer cell lines (HeLa) for their anticancer activities and compared against normal rat cardiac myoblasts (H9C2) cells. Compounds 1-12 were synthesized, with variations in one of the phenyl unit, in a single step by condensation of biaryl-2-carbaldehydes with indole in the presence of para toluenesulfonic acid. Compound 1 exhibited a GI50 value of 11.00 +/- 0.707 MUM and the derivatives, compounds 4 and 11 showed a GI50 value of 8.33 +/- 0.416 MUM and 9.13 +/- 0.177 MUM respectively in HeLa cells and was found to be non-toxic to H9C2 cells up to 20 MUM. Furthermore, compounds 1, 4 and 11 induced caspase dependent cellular apoptosis in a concentration-dependent manner, reduced mitochondrial membrane potential, inhibited the cell migration and downregulated the production of MMP-2 and MMP-9 in HeLa cells. PMID- 26807765 TI - Crocin protects against doxorubicin-induced myocardial toxicity in rats through down-regulation of inflammatory and apoptic pathways. AB - AIM: The clinical application of the chemotherapeutic agent; Doxorubicin (DOX) is limited by its toxic effects on several body organs. The current study was conducted to evaluate the cardiao-protective effects of crocin, a predominant bioactive constituent of Saffron against DOX-induced myocardial toxicity. METHODS: Adult male Sprague Dawley rats received DOX (3.5 mg/kg twice weekly) for 3 weeks with and without daily crocin (10 and 20 mg/kg, orally) for 3 weeks. RESULTS: DOX injection significantly elevated serum levels of aspartate aminotransferase (AST), cardiac specific-creatine kinase (CK-MB), cardiac Troponin T and lactate dehydrogenase (LDH) with impaired electrocardiogram (ECG) profile, indicating DOX-induced myocardial toxicity. Moreover, cardiac specimen examination revealed myocardial inflammatory infiltration with multifocal areas of myocardial degeneration/necrosis. DOX injection significantly increased numbers of active anti-Cd 68 positivity stained cells and significantly-induced myocardial apoptosis. Finally, there was a significant increase in cardiac TNF alpha, IL-1beta and caspase-3 expression associated with significant decrease in IL-10. Crocin treatment resulted in a significant dose dependent attenuation of DOX-induced myocardial toxicity. It improved ECG profile and restored normal cardiac architecture. Furthermore, crocin reduced oxidative stress, enhanced host anti-oxidant defenses and decreased apoptosis as well. Additionally, crocin restored the balance between pro-and anti-inflammatory cytokines. The improvement in biochemical parameters was accompanied by significant myocardial improvement as seen in histopathological specimen. CONCLUSION: Crocin has a cardioprotective effect against DOX-induced cardiomayopathy. Anti-inflammatory, antioxidant and antiapoptic properties of crocin are thought to be involved in the observed cardioprotective effect. PMID- 26807766 TI - Measurement of lacunar bone strains and crack formation during tensile loading by digital volume correlation of second harmonic generation images. AB - The maintenance of healthy bone tissue depends upon the ability of osteocytes to respond to mechanical cues on the cellular level. The combination of digital volume correlation and second harmonic generation microscopy offers the opportunity to investigate the mechanical microenvironment of intact bone on the scale of individual osteocytes. Adult human femurs were imaged under tensile loads of 5 and 15MPa and volumes of approximately 492*429*31MUm(3) were analyzed, along with an image of a bone microcrack under the same loading conditions. Principal strains were significantly higher in three-dimensional digital volume correlation when compared to two-dimensional digital image correlation. The average maximum principal strain magnitude was 5.06-fold greater than the applied global strain, with peak strains of up to 23.14-fold over global strains measured at the borders of osteocyte lacunae. Finally, a microcrack that initiated at an osteocyte lacunae had its greatest tensile strain magnitudes at the crack expansion front in the direction of a second lacunae, but strain at the crack border was reduced to background strain magnitudes upon breaching the second lacunae. This serveed to demonstrate the role of lacunae in initiating, mediating and terminating microcrack growth. PMID- 26807767 TI - Micromechanics and constitutive modeling of connective soft tissues. AB - In this paper, a micromechanical model for connective soft tissues based on the available histological evidences is developed. The proposed model constituents i.e. collagen fibers and ground matrix are considered as hyperelastic materials. The matrix material is assumed to be isotropic Neo-Hookean while the collagen fibers are considered to be transversely isotropic hyperelastic. In order to take into account the effects of tissue structure in lower scales on the macroscopic behavior of tissue, a strain energy density function (SEDF) is developed for collagen fibers based on tissue hierarchical structure. Macroscopic response and properties of tissue are obtained using the numerical homogenization method with the help of ABAQUS software. The periodic boundary conditions and the proposed constitutive models are implemented into ABAQUS using the DISP and the UMAT subroutines, respectively. The existence of the solution and stable material behavior of proposed constitutive model for collagen fibers are investigated based on the poly-convexity condition. Results of the presented micromechanics model for connective tissues are compared and validated with available experimental data. Effects of geometrical and material parameters variation at microscale on macroscopic mechanical behavior of tissues are investigated. The results show that decrease in collagen content of the connective tissues like the tendon due to diseases leads 20% more stretch than healthy tissue under the same load which can results in connective tissue malfunction and hypermobility in joints. PMID- 26807768 TI - Influence of geometry and materials on the axial and torsional strength of the head-neck taper junction in modular hip replacements: A finite element study. AB - The assembly force is important in establishing the mechanical environment at the head-neck taper junction of modular hip replacements. Previous experimental results of the assembled taper junctions with different material combinations (Co 28Cr-6Mo and Ti-6Al-4V) reported similar axial strengths (pull-off loads), but lower torsional strengths (twist-off moments) for the CoCr/CoCr junction. However, mechanics of the junction and the strength behaviour have not been understood yet. A three dimensional finite element model of an isolated femoral head-neck junction was developed to explore the assembly and disassembly procedures, particularly the axial and torsional strengths for different material combinations and geometries. Under the same assembly load, the contacting length between the CoCr head and titanium neck was greater than that of in CoCr/CoCr. The contact length in the titanium neck was more sensitive to the assembly force when compared to the CoCr neck. For instance, with increasing the assembly force from 1890 to 3700N, the contact length increased by 88% for CoCr/Ti and 59% for CoCr/CoCr junctions. The torsional strength of the junction was related to the lateral deformation of the neck material due to the applied moment. The angular mismatch existing between the head and neck components was found to play the main role in the torsional strength of the junction. The smaller mismatch angle the higher torsional strength. It is suggested to consider reducing the mismatch angle, particularly in CoCr/CoCr junctions, and ensure a sufficiently high assembly force is applied by impaction for this combination. PMID- 26807769 TI - Characterization of Ti6Al7Nb alloy foams surface treated in aqueous NaOH and CaCl2 solutions. AB - Ti6Al7Nb alloy foams having 53-73% porosity were manufactured via evaporation of magnesium space holders. A bioactive 1um thick sodium hydrogel titanate layer, NaxH2-xTiyO2y+1, formed after 5M NaOH treatment, was converted to crystalline sodium titanate, Na2TiyO2y+1, as a result of post-heat treatment. On the other hand, subsequent CaCl2 treatment of NaOH treated specimens induced calcium titanate formation. However, heat treatment of NaOH-CaCl2 treated specimens led to the loss of calcium and disappearance of the titanate phase. All of the aforementioned surface treatments reduced yield strengths due to the oxidation of the cell walls of the foams, while elastic moduli remained mostly unchanged. Accordingly, equiaxed dimples seen on the fracture surfaces of as-manufactured foams turned into relatively flat and featureless fracture surfaces after surface treatments. On the other hand, Ca- and Na-rich coating preserved their mechanical stabilities and did not spall during fracture. The relation between mechanical properties of foams and macro-porosity fraction were found to obey a power law. The foams with 63 and 73% porosity met the desired biocompatibility requirements with fully open pore structures and elastic moduli similar to that of bone. In vitro tests conducted in simulated body fluid (SBF) showed that NaOH-heat treated surfaces exhibit the highest bioactivity and allow the formation of Ca-P rich phases having Ca/P ratio of 1.3 to form within 5 days. Although Ca-P rich phases formed only after 15 days on NaOH-CaCl2 treated specimens, the Ca/P ratio was closer to that of apatite found in bone. PMID- 26807770 TI - Fabrication, tribological and corrosion behaviors of ultra-fine grained Co-28Cr 6Mo alloy for biomedical applications. AB - Nickel and carbides free Co-28Cr-6Mo alloy was fabricated by combination of mechanical alloying and warm pressing. The microstructure, mechanical properties, pin-on-disk dry sliding wear and corrosion behavior in simulated physiological solution were investigated. The produced Co-28Cr-6Mo alloy has elongated ultra fine grained (UFG) structure of epsilon-phase with average grain size of 600nm in length and 150nm in thickness. The hardness and modulus were determined to be 8.87+/-0.56GPa and 198.27+/-7.02GPa, respectively. The coefficient of friction upon dry sliding against alumina is pretty close to that of the forged Co-29Cr 6Mo alloy. The initial epsilon-phase and UFG microstructure contribute to reduce the depth of severe plastic deformation region during wear and enable the alloy with excellent wear resistance. The corrosion potential of such UFG Co-Cr-Mo alloy has more positive corrosion potential and much lower corrosion current density than those of ASTM alloy. PMID- 26807771 TI - An exploration of plastic deformation dependence of cell viability and adhesion in metallic implant materials. AB - The relationship between cell viability and adhesion behavior, and micro deformation mechanisms was investigated on austenitic 316L stainless steel samples, which were subjected to different amounts of plastic strains (5%, 15%, 25%, 35% and 60%) to promote a variety in the slip and twin activities in the microstructure. Confocal laser scanning microscopy (CLSM) and field emission scanning electron microscopy (FESEM) revealed that cells most favored the samples with the largest plastic deformation, such that they spread more and formed significant filopodial extensions. Specifically, brain tumor cells seeded on the 35% deformed samples exhibited the best adhesion performance, where a significant slip activity was prevalent, accompanied by considerable slip-twin interactions. Furthermore, maximum viability was exhibited by the cells seeded on the 60% deformed samples, which were particularly designed in a specific geometry that could endure greater strain values. Overall, the current findings open a new venue for the production of metallic implants with enhanced biocompatibility, such that the adhesion and viability of the cells surrounding an implant can be optimized by tailoring the surface relief of the material, which is dictated by the micro-deformation mechanism activities facilitated by plastic deformation imposed by machining. PMID- 26807772 TI - Failure modes of Y-TZP abutments with external hex implant-abutment connection determined by fractographic analysis. AB - Yttria-stabilized tetragonal zirconia (Y-TZP) was introduced as ceramic implant abutments due to its excellent mechanical properties. However, the damage patterns for Y-TZP abutments are limited in the literature. Fractographic analyses can provide insights as to the failure origin and related mechanisms. The purpose of this study was to analyze fractured Y-TZP abutments to establish fractographic patterns and then possible reasons for failure. Thirty two prefabricated Y-TZP abutments on external hex implants were retrieved from a single-load-to failure test according to the ISO 14801. Fractographic analyses were conducted under polarized-light estereo and scanning electro microscopy. The predominant fracture pattern was abutment fracture at the connecting region. Classic fractographic features such as arrest lines, hackle, and twist hackle established that failure started where Y-TZP abutments were in contact with the retention screw edges. The abutment screw design and the loading point were the reasons for localized stress concentration and fracture patterns. PMID- 26807773 TI - Monitoring of hardening and hygroscopic induced strains in a calcium phosphate bone cement using FBG sensor. AB - This study initially deals with the investigation of the induced strains during hardening stage of a self-setting calcium phosphate bone cement using fiber-Bragg grating (FBG) optical sensors. A complementary Scanning Electron Microscopy (SEM) investigation was also conducted at different time intervals of the hardening period and its findings were related to the FBG recordings. From the obtained results, it is demonstrated that the FBG response is affected by the microstructural changes taking place when the bone cement is immersed into the hardening liquid media. Subsequently, the FBG sensor was used to monitor the absorption process and hygroscopic response of the hardened and dried biocement when exposed to a liquid/humid environment. From the FBG-based calculated hygric strains as a function of moisture concentration, the coefficient of moisture expansion (CME) of the examined bone cement was obtained, exhibiting two distinct linear regions. PMID- 26807774 TI - The mechanical influences of the graded distribution in the cross-sectional shape, the stiffness and Poisson's ratio of palm branches. AB - The branching system plays an important role in maintaining the survival of palm trees. Due to the nature of monocots, no additional vascular bundles can be added in the palm tree tissue as it ages. Therefore, the changing of the cross sectional area in the palm branch creates a graded distribution in the mechanical properties of the tissue. In the present work, this graded distribution in the tissue mechanical properties from sheath to petiole were studied with a multi scale modeling approach. Then, the entire palm branch was reconstructed and analyzed using finite element methods. The variation of the elastic modulus can lower the level of mechanical stress in the sheath and also allow the branch to have smaller values of pressure on the other branches. Under impact loading, the enhanced frictional dissipation at the surfaces of adjacent branches benefits from the large Poisson's ratio of the sheath tissue. These findings can help to link the wind resistance ability of palm trees to their graded materials distribution in the branching system. PMID- 26807775 TI - First Use of a New Device for Administration of Buspirone and Acetaminophen to Suppress Shivering During Therapeutic Hypothermia. AB - Therapeutic hypothermia or targeted temperature management has been used after cardiac arrest to improve neurological outcomes and mortality. However, a side effect of temperature modulation is a centrally mediated shivering response. The Columbia Anti-Shivering Protocol sets up a systematic method of intravenous (IV) and oral medication escalation to suppress this response and preserve the benefits of this therapy. We present the case of a 59-year-old male who began shivering after therapeutic hypothermia for cardiac arrest, leading to a persistent rise in core temperature despite adequate sedation. He was also found to have gastric contents similar to coffee grounds through nasogastric tube suction. The shivering was effectively suppressed and the rising core temperature plateaued using rectal acetaminophen and buspirone administered by means of a novel device, the Macy Catheter. Also, when used in conjunction with other protocol-driven medications, the patient was able to achieve a core temperature of 33 degrees C. The Macy Catheter appears to be a useful approach to rectally administer buspirone and acetaminophen, using an easy-to-place, nonsterile atraumatic device that requires no radiographic confirmation of placement. PMID- 26807776 TI - Computer-based magnetic resonance imaging as a tool in clinical diagnosis in neurodegenerative diseases. AB - Magnetic resonance imaging (MRI) is one of the core elements within the differential diagnostic work-up of patients with neurodegenerative diseases such as dementia syndromes, Parkinsonian syndromes, and motor neuron diseases. Currently, computerized MRI analyses are not routinely used for individual diagnosis; however, they have improved the anatomical understanding of pathomorphological alterations in various neurodegenerative diseases by quantitative comparisons between patients and controls at the group level. For multiparametric MRI protocols, including T1-weighted MRI, diffusion-weighted imaging, and intrinsic functional connectivity MRI, the potential as a surrogate marker is a subject of investigation. The additional value of MRI with respect to diagnosis at the individual level and for future disease-modifying multicentre trials remains to be defined. Here, we give an overview of recent applications of multiparametric MRI to patients with various neurodegenerative diseases. Starting from applications at the group level, continuous progress of a transfer to individual diagnostic classification is ongoing. PMID- 26807778 TI - Intense-Field Double Detachment of Electrostatically Bound F(-)(NF3)n Cluster Anions. AB - The interaction of intense laser pulses with size-selected F(-)(NF3)n clusters is experimentally studied. Intense-field double- and multiple-detachment processes in the isolated atomic F(-) anion and in electrostatically bound F(-)(NF3) dimer and F(-)(NF3)2 trimer systems are directly compared. Both dimer and trimer systems are found to exhibit similar enhancement of the highly nonlinear processes, with respect to the atomic system, as reflected in significantly lower saturation intensities. The dependencies of different product channels as a function of laser peak intensity, polarization ellipticity, and laser pulse shape are presented, indicating an efficient nonrescattering mechanism. PMID- 26807777 TI - Near-Stasis in the Long-Term Diversification of Mesozoic Tetrapods. AB - How did evolution generate the extraordinary diversity of vertebrates on land? Zero species are known prior to ~380 million years ago, and more than 30,000 are present today. An expansionist model suggests this was achieved by large and unbounded increases, leading to substantially greater diversity in the present than at any time in the geological past. This model contrasts starkly with empirical support for constrained diversification in marine animals, suggesting different macroevolutionary processes on land and in the sea. We quantify patterns of vertebrate standing diversity on land during the Mesozoic-early Paleogene interval, applying sample-standardization to a global fossil dataset containing 27,260 occurrences of 4,898 non-marine tetrapod species. Our results show a highly stable pattern of Mesozoic tetrapod diversity at regional and local levels, underpinned by a weakly positive, but near-zero, long-term net diversification rate over 190 million years. Species diversity of non-flying terrestrial tetrapods less than doubled over this interval, despite the origins of exceptionally diverse extant groups within mammals, squamates, amphibians, and dinosaurs. Therefore, although speciose groups of modern tetrapods have Mesozoic origins, rates of Mesozoic diversification inferred from the fossil record are slow compared to those inferred from molecular phylogenies. If high speciation rates did occur in the Mesozoic, then they seem to have been balanced by extinctions among older clades. An apparent 4-fold expansion of species richness after the Cretaceous/Paleogene (K/Pg) boundary deserves further examination in light of potential taxonomic biases, but is consistent with the hypothesis that global environmental disturbances such as mass extinction events can rapidly adjust limits to diversity by restructuring ecosystems, and suggests that the gradualistic evolutionary diversification of tetrapods was punctuated by brief but dramatic episodes of radiation. PMID- 26807779 TI - National Characteristics of Emergency Medical Services in Frontier and Remote Areas. AB - Although much is known about EMS care in urban, suburban, and rural settings, only limited national data describe EMS care in isolated and sparsely populated frontier regions. We sought to describe the national characteristics and outcomes of EMS care provided in frontier and remote (FAR) areas in the continental United States (US). We performed a cross-sectional analysis of the 2012 National Emergency Medical Services Information System (NEMSIS) data set, encompassing EMS response data from 40 States. We linked the NEMSIS dataset with Economic Research Service-identified FAR areas, defined as a ZIP Code >60 minutes driving time to an urban center with >50,000 persons. We excluded EMS responses resulting in intercepts, standbys, inter-facility transports, and medical transports. Using odds ratios, t-tests and the Wilcoxon rank-sum test, we compared patient demographics, response characteristics (location type, level of care), clinical impressions, and on-scene death between EMS responses in FAR and non-FAR areas. There were 15,005,588 EMS responses, including 983,286 (7.0%) in FAR and 14,025,302 (93.0%) in non-FAR areas. FAR and non-FAR EMS events exhibited similar median response 5 [IQR 3-10] vs. 5 [3-8] min), scene (14 [10-20] vs. 14 [10-20] min), and transport times (11 [5.,24] vs. 12 [7,19] min). Air medical (1.51% vs. 0.42%; OR 4.15 [95% CI: 4.03-4.27]) and Advanced Life Support care (62.4% vs. 57.9%; OR 1.25 [1.24-1.26]) were more common in FAR responses. FAR responses were more likely to be of American Indian or Alaska Native race (3.99% vs. 0.70%; OR 5.04, 95% CI: 4.97-5.11). Age, ethnicity, location type, and clinical impressions were similar between FAR and non-FAR responses. On-scene death was more likely in FAR than non-FAR responses (12.2 vs. 9.6 deaths/1,000 responses; OR 1.28, 95% CI: 1.25-1.30). Approximately 1 in 15 EMS responses in the continental US occur in FAR areas. FAR EMS responses are more likely to involve air medical or ALS care as well as on-scene death. These data highlight the unique characteristics of FAR EMS responses in the continental US. PMID- 26807780 TI - Localization of Human Copper Transporter 1 in the Eye and its Role in Eales Disease. AB - PURPOSE: Copper (Cu) is an essential trace element; however excess is toxic due to the pro-oxidant activity. Increased intracellular Cu levels in vitreous and monocyte were reported in Eales disease (ED) previously. Copper transporter1 (CTR1) maintains copper homeostasis and hence, we studied the presence of CTR1 in ocular tissues and its role in ED. METHODS: Real-time PCR, ELISA and Western blot experiments were performed in donor eyeballs tissues and PBMCs isolated from controls and ED. Immunostaining were performed for CTR1 from donor eyeballs and one ED case. RESULTS: CTR1 protein was expressed in all ocular tissues. PBMCs showed a three-fold increase in CTR1 protein in ED when compared with controls. Retinal sections from ED patients also revealed increased CTR1 protein expression in retinal tissues, compared with control. CONCLUSIONS: CTR1 was significantly increased in ED when compared with controls, indicating its considerable role in the ED pathology. PMID- 26807781 TI - Nanomaterial-based x-ray sources. AB - Following the recent global excitement and investment in the emerging, and rapidly growing, classes of one and two-dimensional nanomaterials, we here present a perspective on one of the viable applications of such materials: field electron emission based x-ray sources. These devices, which have a notable history in medicine, security, industry and research, to date have almost exclusively incorporated thermionic electron sources. Since the middle of the last century, field emission based cathodes were demonstrated, but it is only recently that they have become practicable. We outline some of the technological achievements of the past two decades, and describe a number of the seminal contributions. We explore the foremost market hurdles hindering their roll-out and broader industrial adoption and summarise the recent progress in miniaturised, pulsed and multi-source devices. PMID- 26807782 TI - In Situ Growth of Prussian Blue Nanostructures at Reduced Graphene Oxide as a Modified Platinum Electrode for Synergistic Methanol Oxidation. AB - Herein, we report a facile synthetic strategy for the in situ growth of Prussian blue nanostructures (PB NSs) at the amine-functionalized silicate sol-gel matrix (TPDT)-RGO composite via the electrostatic interaction. Subsequently, Pt nanostructures are electrodeposited onto the preformed ITO/TPDT-RGO-PB electrode to prepare the RGO/PB/Pt catalyst. The significance of the present method is that the PB NSs are in situ grown by interconnecting the RGO layers, leading to 3D cage-like porous nanostructure. The modified electrodes are characterized by FESEM, EDAX, XRD, XPS, and electrochemical techniques. The RGO/PB/Pt catalyst exhibits synergistic electrocatalytic activity and high stability toward methanol oxidation. The porous nature of the TPDT and PB and unique electron-transfer mediating behavior of PB integrated with RGO in the presence of Pt nanostructures facilitated synergistic electrocatalytic activity for methanol oxidation. PMID- 26807783 TI - Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell. AB - All soluble proteins populate conformational ensembles that together constitute the native state. Their fluctuations in water are intrinsic thermodynamic phenomena, and the distributions of the states on the energy landscape are determined by statistical thermodynamics; however, they are optimized to perform their biological functions. In this review we briefly describe advances in free energy landscape studies of protein conformational ensembles. Experimental (nuclear magnetic resonance, small-angle X-ray scattering, single-molecule spectroscopy, and cryo-electron microscopy) and computational (replica-exchange molecular dynamics, metadynamics, and Markov state models) approaches have made great progress in recent years. These address the challenging characterization of the highly flexible and heterogeneous protein ensembles. We focus on structural aspects of protein conformational distributions, from collective motions of single- and multi-domain proteins, intrinsically disordered proteins, to multiprotein complexes. Importantly, we highlight recent studies that illustrate functional adjustment of protein conformational ensembles in the crowded cellular environment. We center on the role of the ensemble in recognition of small- and macro-molecules (protein and RNA/DNA) and emphasize emerging concepts of protein dynamics in enzyme catalysis. Overall, protein ensembles link fundamental physicochemical principles and protein behavior and the cellular network and its regulation. PMID- 26807784 TI - Identification of infants and preschool children at risk for asthma: predictive scores and biomarkers. AB - PURPOSE OF REVIEW: Predictive asthma scores and biomarkers are important tools that help many physicians in the identification of infants and preschool children at high risk for asthma. Our objective was to review recent data regarding this subject. RECENT FINDINGS: Recently, two new predictive asthma scores were developed with some innovative features, such as the definition of scales of asthma risk. In a systematic review, 12 asthma-predictive models were identified with heterogeneous performance. Prospective studies have shown that elevated fractional concentration of nitric oxide (FeNO) is a strong risk factor for latter asthma among early wheezers, and a predictive asthma score with FeNO values has been proposed. Plasma cytokines and exhaled volatile organic compounds were also identified as potential asthma predictors. SUMMARY: Predictive scores are simple, practical, and inexpensive tools to identify children at high risk for asthma at school age. Whereas some scores are better at identifying asthmatic children, others are better at excluding the diagnosis of asthma. Although promising, clear evidence for FeNO as a robust asthma predictor in comparison to clinical scores is still lacking. Specific IgE and eosinophil counts remain the most consistent biomarkers for the identification of children at risk for asthma, and further studies are necessary to clarify the role of other biomarkers. PMID- 26807785 TI - Empirical modelling to predict the refractive index of human blood. AB - Optical techniques used for the measurement of the optical properties of blood are of great interest in clinical diagnostics. Blood analysis is a routine procedure used in medical diagnostics to confirm a patient's condition. Measuring the optical properties of blood is difficult due to the non-homogenous nature of the blood itself. In addition, there is a lot of variation in the refractive indices reported in the literature. These are the reasons that motivated the researchers to develop a mathematical model that can be used to predict the refractive index of human blood as a function of concentration, temperature and wavelength. The experimental measurements were conducted on mimicking phantom hemoglobin samples using the Abbemat Refractometer. The results analysis revealed a linear relationship between the refractive index and concentration as well as temperature, and a non-linear relationship between refractive index and wavelength. These results are in agreement with those found in the literature. In addition, a new formula was developed based on empirical modelling which suggests that temperature and wavelength coefficients be added to the Barer formula. The verification of this correlation confirmed its ability to determine refractive index and/or blood hematocrit values with appropriate clinical accuracy. PMID- 26807787 TI - Identification of novel 2-(1H-indol-1-yl)-benzohydrazides CXCR4 ligands impairing breast cancer growth and motility. AB - BACKGROUND: Stromal-derived-factor-1 (SDF-1) and the G-protein-coupled receptor CXCR4 are involved in several physiological and pathological processes including breast cancer spread and progression. Several CXCR4 antagonists have currently reached advanced development stages as potential therapeutic agents for different diseases. RESULTS: A small series of novel CXCR4 ligands, based on a 2-(1H-indol 1-yl)-benzohydrazide scaffold, has been designed and synthesized. The interaction with CXCR4-active site was predicted by molecular docking and confirmed by whole cell-based [(125)I]-SDF-1 ligand competition binding assays. One of the synthesized compounds was particularly active in blocking SDF-1-induced breast cancer cell motility, proliferation and downstream signaling activation in different breast cancer cell models and coculture systems. CONCLUSION: The newly synthesized compounds represent suitable leads for the development of innovative therapeutic agents targeting CXCR4. PMID- 26807786 TI - Lung Infection by Human Bocavirus Induces the Release of Profibrotic Mediator Cytokines In Vivo and In Vitro. AB - Human Bocavirus subtype 1 (HBoV1) is associated with respiratory diseases and may contribute to chronic lung diseases by persisting in the infected host. Here the question was addressed if HBoV infections could contribute to fibrogenesis processes as suggested by previously published clinical observations. Cytokine profiles induced by HBoV infection in CuFi-8 air-liquid interphase cell cultures and in bronchoalveolar lavage fluid (BALF) of 20 HBoV-positive and 12 HBoV negative patients were analysed by semi-quantitative Western spot blot analyses. Although lots of cytokines were regulated independently of HBoV status, several cytokines associated with lung fibrosis and tumour development, e.g., EGF, VEGF, TARC (CCL17), TNF-alpha, TNF-beta, TIMP-1, were clearly upregulated in the HBoV positive cohort. These findings suggest that the development of lung fibrosis might be triggered by HBoV induced cytokine expression. PMID- 26807788 TI - Epidemiology and health-related services. AB - PURPOSE OF REVIEW: This article presents recent epidemiologic contributions focusing on gout-related conditions, especially if controversial, to find plausible, despite hypothetical, mechanistic explanations from the clinician perspective. RECENT FINDINGS: The prevalence of gout is increasing, but it is only partially clear that the incidence may be increasing as well. Direct associations of gout with increased risk of diabetes, black races, neurodegenerative disorders, and sugar-enriched foods have been recently questioned. A negative association with smoking has been reported, and new evidence shows that the impact of diet may be independent of obesity. Kidney disease and diuretics have been confirmed to be associated with gout, whereas new data on aging and menopause have come to challenge apparently established disease mechanisms. Regarding treatments, increase in bladder cancer associated with chronic allopurinol use has been reported, and the positive effect of urate lowering treatment on cardiovascular events has been contested. SUMMARY: Epidemiological data in gout-related conditions are still evolving and claim for future cohort or intervention studies to prove causality. Controversies in epidemiological results fertilize the ground for studies to prove mechanisms and causality and provides a unique opportunity for clinical intervention to improve outcomes, especially with regard to treatments. PMID- 26807789 TI - Emerging technologies with potential for objectively evaluating speech recognition skills. AB - Work-related exposure to noise and other ototoxins can cause damage to the cochlea, synapses between the inner hair cells, the auditory nerve fibers, and higher auditory pathways, leading to difficulties in recognizing speech. Procedures designed to determine speech recognition scores (SRS) in an objective manner can be helpful in disability compensation cases where the worker claims to have poor speech perception due to exposure to noise or ototoxins. Such measures can also be helpful in determining SRS in individuals who cannot provide reliable responses to speech stimuli, including patients with Alzheimer's disease, traumatic brain injuries, and infants with and without hearing loss. Cost effective neural monitoring hardware and software is being rapidly refined due to the high demand for neurogaming (games involving the use of brain-computer interfaces), health, and other applications. More specifically, two related advances in neuro-technology include relative ease in recording neural activity and availability of sophisticated analysing techniques. These techniques are reviewed in the current article and their applications for developing objective SRS procedures are proposed. Issues related to neuroaudioethics (ethics related to collection of neural data evoked by auditory stimuli including speech) and neurosecurity (preservation of a person's neural mechanisms and free will) are also discussed. PMID- 26807790 TI - Methylmalonic Acid and Homocysteine as Indicators of Vitamin B-12 Deficiency in Cancer. AB - BACKGROUND/AIMS: Normal or high serum vitamin B-12 levels can sometimes be seen in a B-12 deficient state, and can therefore be misleading. High levels of Methymalonic Acid (MMA) and Homocysteine (HC) have been identified as better indicators of B-12 deficiency than the actual serum B-12 level itself. We evaluated the prevalence of vitamin B-12 deficiency using appropriate cut-off levels of vitamin B-12, MMA and HC, and determined the relationship between serum levels of vitamin B-12, MMA and HC in cancer. METHODS: This is a cross-sectional study using a consecutive case series of 316 cancer patients first seen at Cancer Treatment Centers of America(r) (CTCA) at Midwestern Regional Medical Center between April 2014 and June 2014. All patients were evaluated at baseline for vitamin B-12 (pg/mL), MMA (nmol/L) and HC (MUmol/L) levels. In accordance with previously published research, the following cut-offs were used to define vitamin B-12 deficiency: <300 pg/mL for vitamin B-12, >260 nmol/L for MMA and >12 MUmol/L for HC. The relationship between B-12, MMA and HC was evaluated using Spearman's rho correlation coefficient and cross-tabulation analysis. Receiver Operating Characteristic (ROC) curves were estimated using the non-parametric method to further evaluate the diagnostic accuracy of vitamin B-12 using Fedosov quotient as the "gold standard". RESULTS: Mean age at presentation was 52.5 years. 134 (42.4%) patients were males while 182 (57.6%) were females. Median vitamin B-12, MMA and HC levels were 582.5 pg/mL, 146.5 nmol/L and 8.4 MUmol/L respectively. Of 316 patients, 28 (8.9%) were vitamin B-12 deficient based on vitamin B-12 (<300 pg/mL), 34 (10.8%) were deficient based on MMA (>260 nmol/L) while 55 (17.4%) were deficient based on HC (>12 MUmol/L). Correlation analysis revealed a significant weak negative correlation between vitamin B-12 and MMA (rho = -0.22) as well as B-12 and HC (rho = -0.35). ROC curves suggested MMA to have the best discriminatory power in predicting B-12 deficiency. CONCLUSION: Vitamin B-12 is poorly correlated with MMA and HC in cancer. Using serum vitamin B-12 alone to evaluate B-12 status in cancer may fail to identify those with functional deficiency. A thorough clinical assessment is important to identify patients that may have risk factors and/or symptoms suggestive of deficiency. These patients should have additional testing of MMA and HC regardless of their B-12 levels. PMID- 26807791 TI - Backscattered electron image of osmium-impregnated/macerated tissues as a novel technique for identifying the cis-face of the Golgi apparatus by high-resolution scanning electron microscopy. AB - The osmium maceration method with scanning electron microscopy (SEM) enabled to demonstrate directly the three-dimensional (3D) structure of membranous cell organelles. However, the polarity of the Golgi apparatus (that is, the cis-trans axis) can hardly be determined by SEM alone, because there is no appropriate immunocytochemical method for specific labelling of its cis- or trans-faces. In the present study, we used the osmium impregnation method, which forms deposits of reduced osmium exclusively in the cis-Golgi elements, for preparation of specimens for SEM. The newly developed procedure combining osmium impregnation with subsequent osmium maceration specifically visualised the cis-elements of the Golgi apparatus, with osmium deposits that were clearly detected by backscattered electron-mode SEM. Prolonged osmication by osmium impregnation (2% OsO4 solution at 40 degrees C for 40 h) and osmium maceration (0.1% OsO4 solution at 20 degrees C for 24 h) did not significantly impair the 3D ultrastructure of the membranous cell organelles, including the Golgi apparatus. This novel preparation method enabled us to determine the polarity of the Golgi apparatus with enough information about the surrounding 3D ultrastructure by SEM, and will contribute to our understanding of the global organisation of the entire Golgi apparatus in various differentiated cells. PMID- 26807792 TI - Therapeutic Effects of Tangshen Formula on Diabetic Nephropathy in Rats. AB - OBJECTIVE: Inflammation and fibrosis are essential promoters in the pathogenesis of diabetic nephropathy (DN) in type 2 diabetes. The present study examined the anti-inflammation and anti-fibrosis effect of Tangshen Formula (TSF), a traditional Chinese medicine, on DN. RESEARCH DESIGN AND METHODS: Protective role of TSF in DN was examined in a rat model of type 2 DN that was established by high-fat diet-fed and low-dose-streptozotocin injection. TSF was suspended in 0.5% CMC-Na solution and delivered by oral gavage at a dosage of 1.67g/Kg body weight/day. The therapeutic effects and mechanisms of TSF on diabetic kidney injury were examined. RESULTS: We found that TSF treatment for 20 weeks attenuated DN by significantly inhibiting urinary excretion of albumin and renal histological injuries. These beneficial effects were associated with an inactivation of NF-kappaB signaling, thereby blocking the upregulation of pro inflammatory cytokines (IL-1beta, TNFalpha), chemokine (MCP-1), and macrophage infiltration in the TSF-treated rats with type 2 DN. In addition, TSF treatment also inactivated TGF-beta/Smad3 signaling and therefore suppressed renal fibrosis including expressions of fibronectin, collagen I, and collagen IV. Further studies revealed that the inhibitory effect of TSF on TGF-beta/Smad3 and NF kappaB signaling in DN was associated with inhibition of Smurf2-dependent ubiquitin degradation of Smad7. CONCLUSIONS: The present study reveals that TSF has therapeutic potential for type 2 DN in rats. Blockade of NF-kappaB-driven renal inflammation and TGF-beta/Smad3-mediated renal fibrosis by preventing the Smurf2-mediated Smad7 degradation pathway may be mechanisms through which TSF inhibits type 2 DN. PMID- 26807794 TI - Redo mitral valve replacement through a right mini-thoracotomy with an unclamped aorta. AB - Redo cardiac surgery represents a clinical challenge due to a higher rate of perioperative morbidity and mortality. Mitral valve (MV) re operations can particularly be demanding in patients with patent coronary grafts, previous aortic valve replacement, calcified aorta or complications following a previous operation (abscesses, leaks or thrombosis). In this article we describe our technique to manage complex mitral reoperations using a minimally invasive approach, moderate hypothermia and avoiding aortic cross-clamping. Minimally invasive procedures with an unclamped aorta have the potential to combine the benefits of less invasive access and continuous myocardial perfusion. The advantage of a right mini-thoracotomy is the avoidance of sternal re-entry and limited dissection of adhesions, reducing the risk of cardiac structures or patent graft injury. Moderate hypothermia and continuous blood perfusion can guarantee adequate myocardial protection particularly in the case of patent grafts, decreasing the dangers of an incomplete or imperfect aortic clamping at mild hypothermia and potential lesions due to demanding clamp placing. Complex MV reoperations can be safely and effectively performed through a smaller right thoracotomy in the fourth intercostal space with an unclamped aorta. PMID- 26807793 TI - State Anxiety and Nonlinear Dynamics of Heart Rate Variability in Students. AB - OBJECTIVES: Clinical and experimental research studies have demonstrated that the emotional experience of anxiety impairs heart rate variability (HRV) in humans. The present study investigated whether changes in state anxiety (SA) can also modulate nonlinear dynamics of heart rate. METHODS: A group of 96 students volunteered to participate in the study. For each student, two 5-minute recordings of beat intervals (RR) were performed: one during a rest period and one just before a university examination, which was assumed to be a real-life stressor. Nonlinear analysis of HRV was performed. The Spielberger's State-Trait Anxiety Inventory was used to assess the level of SA. RESULTS: Before adjusting for heart rate, a Wilcoxon matched pairs test showed significant decreases in Poincare plot measures, entropy, largest Lyapunov exponent (LLE), and pointwise correlation dimension (PD2), and an increase in the short-term fractal-like scaling exponent of detrended fluctuation analysis (alpha1) during the exam session, compared with the rest period. A Pearson analysis indicated significant negative correlations between the dynamics of SA and Poincare plot axes ratio (SD1/SD2), and between changes in SA and changes in entropy measures. A strong negative correlation was found between the dynamics of SA and LLE. A significant positive correlation was found between the dynamics of SA and alpha1. The decreases in Poincare plot measures (SD1, complex correlation measure), entropy measures, and LLE were still significant after adjusting for heart rate. Corrected alpha1 was increased during the exam session. As before, the dynamics of adjusted LLE was significantly correlated with the dynamics of SA. CONCLUSIONS: The qualitative increase in SA during academic examination was related to the decrease in the complexity and size of the Poincare plot through a reduction of both the interbeat interval and its variation. PMID- 26807795 TI - Interaction between osseous and non-osseous vibratory stimulation of the human cadaveric head. AB - Bone conduction (BC) stimulation can be applied by vibration to the bony or skin covered skull (osseous BC), or on soft tissue such as the neck (non-osseous BC). The interaction between osseous and non-osseous bone conduction pathways is assessed in this study. The relation between bone vibrations measured at the cochlear promontory and the intracranial sound pressure for stimulation directly on the dura and for stimulation at the mastoid between 0.2 and 10 kHz was compared. First, for stimulation on the dura, varying the static coupling force of the BC transducer on the dura had only a small effect on promontory vibration. Second, the presence or absence of intracranial fluid did not affect promontory vibration for stimulation on the dura. Third, stimulation on the mastoid elicited both promontory vibration and intracranial sound pressure. Stimulation on the dura caused intracranial sound pressure to a similar extent above 0.5 kHz compared to stimulation on the mastoid, while promontory vibration was less by 20 40 dB. From these findings, we conclude that intracranial sound pressure (non osseous BC) only marginally affects bone vibrations measured on the promontory (osseous BC), whereas skull vibrations affect intracranial sound pressure. PMID- 26807796 TI - Mechanical damage of tympanic membrane in relation to impulse pressure waveform - A study in chinchillas. AB - Mechanical damage to middle ear components in blast exposure directly causes hearing loss, and the rupture of the tympanic membrane (TM) is the most frequent injury of the ear. However, it is unclear how the severity of injury graded by different patterns of TM rupture is related to the overpressure waveforms induced by blast waves. In the present study, the relationship between the TM rupture threshold and the impulse or overpressure waveform has been investigated in chinchillas. Two groups of animals were exposed to blast overpressure simulated in our lab under two conditions: open field and shielded with a stainless steel cup covering the animal head. Auditory brainstem response (ABR) and wideband tympanometry were measured before and after exposure to check the hearing threshold and middle ear function. Results show that waveforms recorded in the shielded case were different from those in the open field and the TM rupture threshold in the shielded case was lower than that in the open field (3.4 +/- 0.7 vs. 9.1 +/- 1.7 psi or 181 +/- 1.6 vs. 190 +/- 1.9 dB SPL). The impulse pressure energy spectra analysis of waveforms demonstrates that the shielded waveforms include greater energy at high frequencies than that of the open field waves. Finally, a 3D finite element (FE) model of the chinchilla ear was used to compute the distributions of stress in the TM and the TM displacement with impulse pressure waves. The FE model-derived change of stress in response to pressure loading in the shielded case was substantially faster than that in the open case. This finding provides the biomechanical mechanisms for blast induced TM damage in relation to overpressure waveforms. The TM rupture threshold difference between the open and shielded cases suggests that an acoustic role of helmets may exist, intensifying ear injury during blast exposure. PMID- 26807797 TI - Comparison of mouse minimum audible angle determined in prepulse inhibition and operant conditioning procedures. AB - Both reward based operant conditioning (OC) and reflex-based prepulse inhibition (PPI) procedures are used in sound localisation studies in mice. Since the results of both procedures are compared in the literature, it is important to assess whether they provide similar results if the same stimulus paradigm is applied. Here, we compare the sensitivity of C57BL/6 mice in OC and PPI procedures for detecting a switch in speaker location using broadband and narrowband noise stimuli and determined their minimum audible angle (MAA). In the OC procedure, we calculated d' values from the hit and false alarm rates. In the PPI procedure, we calculated the area under ROC curves from the startle response amplitudes and derived da values to obtain a sensitivity measure that corresponds to d'. For both procedures, the mean sensitivity to the speaker switch increased with an increase in angular separation. For broadband noise stimuli, a d' of up to 3.3 (OC) and a da of up to 1.1 (PPI) were observed at large speaker separations. Narrowband noise stimuli resulted in lower sensitivities in both procedures, resulting in a maximum d' of 2.0 (OC) and a maximum da of 0.3 (PPI). Using a sensitivity of 1.0 as the threshold criterion, broadband noise MAAs in the range from 32 degrees to 46 degrees were observed in the OC procedure whereas a broadband noise MAAs of 108 degrees or higher were observed in the PPI procedure. In the OC procedure, narrowband noise MAAs in the range from 37 degrees to 62 degrees were observed. In the PPI procedure, no narrowband noise MAA could be determined since none of the subjects reached the threshold. Thus, OC procedures result in a better performance of the subjects in the sound localization task than PPI procedures, challenging the view that both procedures can be used interchangeably. PMID- 26807798 TI - Occurrence, Virulence Factors, Antimicrobial Resistance, and Genotyping of Staphylococcus aureus Strains Isolated from Chicken Products and Humans. AB - Staphylococcus aureus in food is a consequence of inadequate hygienic handling and processing, posing a potential risk to public health. The current study aimed to characterize virulence factors, as well as antimicrobial resistance of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) isolated from retail chicken products and hand swabs from vendors in Egypt. In addition, genetic relatedness of the isolates from chicken and humans was evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using protein A as a target. A total of 110 samples were collected from chicken products (n = 80) and vendors (n = 30). Overall, 30 (37.5%) chicken products samples were positive for S. aureus, whereas hand swabs from meat handlers revealed that 18 (60%) were positive. Ten MRSA strains were characterized by the presence of the mecA gene, comprising seven isolates from chicken and three from humans. Virulence-associated factors were evaluated by PCR, revealing that 31.3% of S. aureus isolates harbored the Panton-Valentine leukocidin (PVL) gene, whereas 10.4% were positive for the sea and sed genes each, and only two isolates were positive for gamma-hemolysin-associated gene. Genotyping using spa PCR-RFLP showed identical restriction banding patterns of MRSA isolates of human and chicken meat origin, indicating the genetic relatedness of the isolates. To the best of our knowledge, this is the first study to characterize PVL-positive MRSA from chicken products and to utilize spa-RFLP for evaluating the genetic relatedness between MRSA of human and chicken origin in Egypt. PMID- 26807800 TI - Reversible Cerebral Vasoconstriction Syndrome Presenting With Visual Field Defects. AB - A 45-year-old woman with a history of depression and anxiety, treated with selective serotonin reuptake inhibitors (SSRIs), experienced acute, recurrent, and severe bifrontal headaches. Over time, she developed a left homonymous hemianopia and mental status changes. MRA revealed segmental vasoconstriction of cerebral arteries in multiple vascular distributions. She was treated with a calcium-channel blocker and magnesium, and there was resolution of her symptoms and cerebrovascular changes. Her clinical course and neuroimaging findings were consistent with reversible cerebral vasoconstriction syndrome. Although rare, this disorder frequently manifests with visual complaints. Although the prognosis is generally favorable, patients with this syndrome require prompt diagnosis and care directed to avoid complications including stroke, seizure, and subarachnoid hemorrhage. PMID- 26807799 TI - Delineating the Association between Heavy Postpartum Haemorrhage and Postpartum Depression. AB - OBJECTIVES: To explore the association between postpartum haemorrhage (PPH) and postpartum depression (PPD), taking into account the role of postpartum anaemia, delivery experience and psychiatric history. METHODS: A nested cohort study (n = 446), based on two population-based cohorts in Uppsala, Sweden. Exposed individuals were defined as having a bleeding of >=1000 ml (n = 196) at delivery, and non-exposed individuals as having bleeding of <650 ml (n = 250). Logistic regression models with PPD symptoms (Edinburgh Postnatal Depression scale (EPDS) score >= 12) as the outcome variable and PPH, anaemia, experience of delivery, mood during pregnancy and other confounders as exposure variables were undertaken. Path analysis using Structural Equation Modeling was also conducted. RESULTS: There was no association between PPH and PPD symptoms. A positive association was shown between anaemia at discharge from the maternity ward and the development of PPD symptoms, even after controlling for plausible confounders (OR = 2.29, 95%CI = 1.15-4.58). Path analysis revealed significant roles for anaemia at discharge, negative self-reported delivery experience, depressed mood during pregnancy and postpartum stressors in increasing the risk for PPD. CONCLUSION: This study proposes important roles for postpartum anaemia, negative experience of delivery and mood during pregnancy in explaining the development of depressive symptoms after PPH. PMID- 26807801 TI - The Latin American laws of correct nutrition: Review, unified interpretation, model and tools. AB - BACKGROUND: The "Laws of Correct Nutrition": the Law of Quantity, the Law of Quality, the Law of Harmony and the Law of Adequacy, provide the basis of a proper diet, i.e. one that provides the body with the energy required and nutrients it needs for daily activities and maintenance of vital functions. For several decades, these Laws have been the basis of nourishing menus designed in Latin America; however, they are stated in a colloquial language, which leads to differences in interpretation and ambiguities for non-experts and even experts in the field. METHODS: We present a review of the different interpretations of the Laws and describe a consensus. We represent concepts related to nourishing menu design employing the Unified Modeling Language (UML). We formalize the Laws using the Object Constraint Language (OCL). We design a nourishing menu for a particular user through enforcement of the Laws. RESULTS: We designed a domain model with the essential elements to plan a nourishing menu and we expressed the necessary constraints to make the model's behavior conform to the four Laws. We made a formal verification and validation of the model via USE (UML-based Specification Environment) and we developed a software prototype for menu design under the Laws. CONCLUSION: Diet planning is considered as an art but consideration should be given to the need for a set of strict rules to design adequate menus. Thus, we model the "Laws of Nutrition" as a formal basis and standard framework for this task. PMID- 26807802 TI - A patient-specific EMG-driven neuromuscular model for the potential use of human inspired gait rehabilitation robots. AB - A patient-specific electromyography (EMG)-driven neuromuscular model (PENm) is developed for the potential use of human-inspired gait rehabilitation robots. The PENm is modified based on the current EMG-driven models by decreasing the calculation time and ensuring good prediction accuracy. To ensure the calculation efficiency, the PENm is simplified into two EMG channels around one joint with minimal physiological parameters. In addition, a dynamic computation model is developed to achieve real-time calculation. To ensure the calculation accuracy, patient-specific muscle kinematics information, such as the musculotendon lengths and the muscle moment arms during the entire gait cycle, are employed based on the patient-specific musculoskeletal model. Moreover, an improved force-length velocity relationship is implemented to generate accurate muscle forces. Gait analysis data including kinematics, ground reaction forces, and raw EMG signals from six adolescents at three different speeds were used to evaluate the PENm. The simulation results show that the PENm has the potential to predict accurate joint moment in real-time. The design of advanced human-robot interaction control strategies and human-inspired gait rehabilitation robots can benefit from the application of the human internal state provided by the PENm. PMID- 26807804 TI - How residency duration affects the outcome of a territorial contest: Complementary game-theoretic models. AB - While the first individuals to discover and maintain territories are generally respected as owners, under some conditions there may be ambiguity as to who got there first. Here we attempt to understand the evolutionary consequences of this ambiguity by developing a pair of game-theoretic models in which we explicitly consider rival residency-based claims to ownership. Following earlier qualitative explanations for residency effects, we assume that either the value of the territory (Model A) or an interloper's self-belief that it is the owner (Model B) increases with duration of residency. Model A clearly demonstrates that if the value of a territory increases to a resident over time, so should its motivation to fight in terms of the effort it invests in fighting. Indeed, only a small increase in territory value with residency duration can be sufficient for longer established residents to win disputes, even without any arbitrary convention or other form of priority effect. Likewise, Model B shows that the observed increase in fighting persistence with residency duration can be readily explained as a consequence of increasing confidence on behalf of the interloper that it is the rightful owner. Collectively, the models help to explain some general findings long observed by empiricists, and shed light on the nature of conflicts that can arise when individuals do not have complete information about rival claims to ownership. PMID- 26807803 TI - Individual-Based Model of Microbial Life on Hydrated Rough Soil Surfaces. AB - Microbial life in soil is perceived as one of the most interesting ecological systems, with microbial communities exhibiting remarkable adaptability to vast dynamic environmental conditions. At the same time, it is a notoriously challenging system to understand due to its complexity including physical, chemical, and biological factors in synchrony. This study presents a spatially resolved model of microbial dynamics on idealised rough soil surfaces represented as patches with different (roughness) properties that preserve the salient hydration physics of real surfaces. Cell level microbial interactions are considered within an individual-based formulation including dispersion and various forms of trophic dependencies (competition, mutualism). The model provides new insights into mechanisms affecting microbial community dynamics and gives rise to spontaneous formation of microbial community spatial patterns. The framework is capable of representing many interacting species and provides diversity metrics reflecting surface conditions and their evolution over time. A key feature of the model is its spatial scalability that permits representation of microbial processes from cell-level (micro-metric scales) to soil representative volumes at sub-metre scales. Several illustrative examples of microbial trophic interactions and population dynamics highlight the potential of the proposed modelling framework to quantitatively study soil microbial processes. The model is highly applicable in a wide range spanning from quantifying spatial organisation of multiple species under various hydration conditions to predicting microbial diversity residing in different soils. PMID- 26807805 TI - A monoecious and diploid Moran model of random mating. AB - An exact Markov chain is developed for a Moran model of random mating for monoecious diploid individuals with a given probability of self-fertilization. The model captures the dynamics of genetic variation at a biallelic locus. We compare the model with the corresponding diploid Wright-Fisher (WF) model. We also develop a novel diffusion approximation of both models, where the genotype frequency distribution dynamics is described by two partial differential equations, on different time scales. The first equation captures the more slowly varying allele frequencies, and it is the same for the Moran and WF models. The other equation captures departures of the fraction of heterozygous genotypes from a large population equilibrium curve that equals Hardy-Weinberg proportions in the absence of selfing. It is the distribution of a continuous time Ornstein Uhlenbeck process for the Moran model and a discrete time autoregressive process for the WF model. One application of our results is to capture dynamics of the degree of non-random mating of both models, in terms of the fixation index fIS. Although fIS has a stable fixed point that only depends on the degree of selfing, the normally distributed oscillations around this fixed point are stochastically larger for the Moran than for the WF model. PMID- 26807806 TI - pSuc-Lys: Predict lysine succinylation sites in proteins with PseAAC and ensemble random forest approach. AB - Being one type of post-translational modifications (PTMs), protein lysine succinylation is important in regulating varieties of biological processes. It is also involved with some diseases, however. Consequently, from the angles of both basic research and drug development, we are facing a challenging problem: for an uncharacterized protein sequence having many Lys residues therein, which ones can be succinylated, and which ones cannot? To address this problem, we have developed a predictor called pSuc-Lys through (1) incorporating the sequence coupled information into the general pseudo amino acid composition, (2) balancing out skewed training dataset by random sampling, and (3) constructing an ensemble predictor by fusing a series of individual random forest classifiers. Rigorous cross-validations indicated that it remarkably outperformed the existing methods. A user-friendly web-server for pSuc-Lys has been established at http://www.jci bioinfo.cn/pSuc-Lys, by which users can easily obtain their desired results without the need to go through the complicated mathematical equations involved. It has not escaped our notice that the formulation and approach presented here can also be used to analyze many other problems in computational proteomics. PMID- 26807807 TI - Comparative modeling of combined transport of water and graded-size molecules across the glomerular capillary wall. AB - Chronic kidney disease is a common and growing problem worldwide that necessitates recognition of individual risk and appropriate laboratory testing before its progression to end-stage renal failure, requiring dialysis or transplantation for survival. Clearance studies using various graded-size probe molecules established that the passage of molecules/proteins across the glomerular capillary barrier of mammalian kidneys is increasingly restricted as their size increase. Few mathematical models were developed to describe the dynamics of the size-selective functions of macromolecules across membranes and gelatins. In the present study, we compare the behavior of three mathematical descriptions for the Fiber Matrix theory, an Extended Fiber Matrix theory, and an Alternative Statistical Physics analysis to describe the size-selective function of the glomerular capillary barrier; using mainly its hemodynamic, morphometric and hydrodynamic variables; in two experimental rat models. The glomerular basement membrane was represented as a homogeneous three-dimensional network of fibers of uniform length (Lf), radius (Rf), total fractional solid volume of fibers (Vf) and characteristic Darcy permeability. The models were appropriate for simulating in vivo fractional clearance data of neutral Dextran and Ficoll macromolecules from two experimental rat models. We believe that the Lf, Rf and Vf best-fit numerical values may signify new insights for the diagnosis of human nephropathies. PMID- 26807808 TI - Mathematical models of radiation action on living cells: From the target theory to the modern approaches. A historical and critical review. AB - Cell survival is conventionally defined as the capability of irradiated cells to produce colonies. It is quantified by the clonogenic assays that consist in determining the number of colonies resulting from a known number of irradiated cells. Several mathematical models were proposed to describe the survival curves, notably from the target theory. The Linear-Quadratic (LQ) model, which is to date the most frequently used model in radiobiology and radiotherapy, dominates all the other models by its robustness and simplicity. Its usefulness is particularly important because the ratio of the values of the adjustable parameters, alpha and beta, on which it is based, predicts the occurrence of post-irradiation tissue reactions. However, the biological interpretation of these parameters is still unknown. Throughout this review, we revisit and discuss historically, mathematically and biologically, the different models of the radiation action by providing clues for resolving the enigma of the LQ model. PMID- 26807809 TI - Invasion speeds of Triatoma dimidiata, vector of Chagas disease: An application of orthogonal polynomials method. AB - Demographic processes and spatial dispersal of Triatoma dimidiata, a triatomine species vector of Chagas disease, are modeled by integrodifference equations to estimate invasion capacity of this species under different ecological conditions. The application of the theory of orthogonal polynomials and the steepest descent method applied to these equations, allow a good approximation of the abundance of the adult female population and the invasion speed. We show that: (1) under the same mean conditions of demography and dispersal, periodic spatial dispersal results in an invasion speed 2.5 times larger than the invasion speed when spatial dispersal is continuous; (2) when the invasion speed of periodic spatial dispersal is correlated to adverse demographic conditions, it is 34.7% higher as compared to a periodic dispersal that is correlated to good demographic conditions. From our results we conclude, in terms of triatomine population control, that the invasive success of T. dimidiata may be most sensitive to the probability of transition from juvenile to adult stage. We discuss our main theoretical predictions in the light of observed data in different triatomines species found in the literature. PMID- 26807811 TI - Spectrum of Microbial Diseases and Resistance Patterns at a Private Teaching Hospital in Kenya: Implications for Clinical Practice. AB - BACKGROUND: Accurate local prevalence of microbial diseases and microbial resistance data are vital for optimal treatment of patients. However, there are few reports of these data from developing countries, especially from sub-Saharan Africa. The status of Aga Khan University Hospital Nairobi as an internationally accredited hospital and a laboratory with an electronic medical record system has made it possible to analyze local prevalence and antimicrobial susceptibility data and compare it with other published data. METHODS: We have analyzed the spectrum of microbial agents and resistance patterns seen at a 300 bed tertiary private teaching hospital in Kenya using microbial identity and susceptibility data captured in hospital and laboratory electronic records between 2010 and 2014. RESULTS: For blood isolates, we used culture collection within the first three days of hospitalization as a surrogate for community onset, and within that group, Escherichia coli was the most common, followed by Staphylococcus aureus. In contrast, Candida spp. and Klebsiella pneumoniae were the most common hospital onset causes of bloodstream infection. Antimicrobial resistance rates for the most commonly isolated Gram negative organisms was higher than many recent reports from Europe and North America. In contrast, Gram positive resistance rates were quite low, with 94% of S. aureus being susceptible to oxacillin and only rare isolates of vancomycin-resistant enterococci. CONCLUSIONS: The current report demonstrates high rates of antimicrobial resistance in Gram negative organisms, even in outpatients with urinary tract infections. On the other hand, rates of resistance in Gram positive organisms, notably S. aureus, are remarkably low. A better understanding of the reasons for these trends may contribute to ongoing efforts to combat antimicrobial resistance globally. PMID- 26807810 TI - Endoplasmic reticulum-resident Rab8A GTPase is involved in phagocytosis in the protozoan parasite Entamoeba histolytica. AB - Phagocytosis is indispensable for the pathogenesis of the intestinal protozoan parasite Entamoeba histolytica. Here, we showed that in E. histolytica Rab8A, which is generally involved in trafficking from the trans-Golgi network to the plasma membrane in other organisms but was previously identified in phagosomes of the amoeba in the proteomic analysis, primarily resides in the endoplasmic reticulum (ER) and participates in phagocytosis. We demonstrated that down regulation of EhRab8A by small antisense RNA-mediated transcriptional gene silencing remarkably reduced adherence and phagocytosis of erythrocytes, bacteria and carboxylated latex beads. Surface biotinylation followed by SDS-PAGE analysis revealed that the surface expression of several proteins presumably involved in target recognition was reduced in the EhRab8A gene-silenced strain. Further, overexpression of wild-type EhRab8A augmented phagocytosis, whereas expression of the dominant-negative form of EhRab8A resulted in reduced phagocytosis. These results indicated that EhRab8A regulates transport of surface receptor(s) for the prey from the ER to the plasma membrane. To our knowledge, this is the first report that the ER-resident Rab GTPase is involved in phagocytosis through the regulation of trafficking of a surface receptor, supporting a premise of direct involvement of the ER in phagocytosis. PMID- 26807812 TI - Sex and age differences in the antidepressant-like effect of fluoxetine in the forced swim test. AB - This study compared in males and females of three representative ages: young adults (3-5months old), middle-aged (12-15months old) and senescent (23-25months old) the antidepressant-like effect of fluoxetine (FLX, 5.0 and 10mg/kg) in the forced swim test (FST). Intact (non gonadectomized) rats were evaluated. Young adult females were chosen in proestrus/estrus or in metestrus/diestrus, while middle-aged and senescent females were selected in metestrus/diestrus. Locomotion and motor coordination were also recorded. Under basal conditions (without FLX), young adult and middle-aged females showed less immobility than males. This sex difference disappeared at senescence because males diminished their levels of immobility. Thus, senescent males showed lower immobility than middle-aged and young males. FLX (5 and 10mg/kg) produced similar actions in young females irrespective of their estrous cycle phase, therefore, these subgroups were pooled in a single one. Young adult and middle aged females clearly responded to 5 and 10mg/kg of FLX with a reduction in immobility, while young adult and middle-aged males only did to 10mg/kg. In senescent females 10mg/kg FLX reduced immobility. Remarkably, in senescent males this FLX dose did not produce an antidepressant like effect. FLX marginally affected locomotion; however, at its highest dose (10mg/kg), and only in senescent males, interfered with motor coordination tested in the rotarod. These data show that sex and aging influence behavioral despair without treatment and after FLX. PMID- 26807813 TI - Effect of Ocean Acidification on Organic and Inorganic Speciation of Trace Metals. AB - Rising concentrations of atmospheric carbon dioxide are causing acidification of the oceans. This results in changes to the concentrations of key chemical species such as hydroxide, carbonate and bicarbonate ions. These changes will affect the distribution of different forms of trace metals. Using IPCC data for pCO2 and pH under four future emissions scenarios (to the year 2100) we use a chemical speciation model to predict changes in the distribution of organic and inorganic forms of trace metals. Under a scenario where emissions peak after the year 2100, predicted free ion Al, Fe, Cu, and Pb concentrations increase by factors of up to approximately 21, 2.4, 1.5, and 2.0 respectively. Concentrations of organically complexed metal typically have a lower sensitivity to ocean acidification induced changes. Concentrations of organically complexed Mn, Cu, Zn, and Cd fall by up to 10%, while those of organically complexed Fe, Co, and Ni rise by up to 14%. Although modest, these changes may have significance for the biological availability of metals given the close adaptation of marine microorganisms to their environment. PMID- 26807814 TI - Linking existing in vitro dermal absorption data to physicochemical properties: Contribution to the design of a weight-of-evidence approach for the safety evaluation of cosmetic ingredients with low dermal bioavailability. AB - To characterize the risk of cosmetic ingredients when threshold toxicity is assumed, often the "margin of safety" (MoS) is calculated. This uncertainty factor is based on the systemic no observable (adverse) effect level (NO(A)EL) which can be derived from in vivo repeated dose toxicity studies. As in vivo studies for the purpose of the cosmetic legislation are no longer allowed in Europe and a validated in vitro alternative is not yet available, it is no longer possible to derive a NO(A)EL value for a new cosmetic ingredient. Alternatively, cosmetic ingredients with a low dermal bioavailability might not need repeated dose data, as internal exposure will be minimal and systemic toxicity might not be an issue. This study shows the possibility of identifying compounds suspected to have a low dermal bioavailability based on their physicochemical properties (molecular weight, melting point, topological polar surface area and log P) and their in vitro dermal absorption data. Although performed on a limited number of compounds, the study suggests a strategic opportunity to support the safety assessor's reasoning to omit a MoS calculation and to focus more on local toxicity and mutagenicity/genotoxicity for ingredients for which limited systemic exposure is to be expected. PMID- 26807815 TI - Experimental Endoscopic Angular Domains of Transnasal and Transoral Routes to the Craniovertebral Junction: Light and Shade. AB - STUDY DESIGN: We investigate on the surgical reliability of nasal palatine line for the transnasal approach and introduce a conceptually analogue radiological line as a reliable predictor of the maximal superior extension of the transoral approach. We have also compared radiological and surgical lines to find possible radiological references points to predict preoperatively the maximal extent of superior dissection for the transoral approach. OBJECTIVE: After comparing the surgical exposition angle and the working channel volume of both the approaches in our previous article, now we compare the radiological (theoretical) with the "surgical" (effective) Nasopalatine line and the latter with the recently introduced Nasal Axial Line. We conceived a radiological line with a similar significance for the transoral approach and we called it Mandibulopalatine line; then we compared the radiological with the "surgical" one. SUMMARY OF BACKGROUND DATA: Endoscopy represents both an alternative and a useful complement to the standard microsurgical approach to the anterior craniovertebral junction (CVJ). Both the surgical routes have a limitation caused by the hard palate. METHODS: Ten fresh nonperfused cadavers were studied. Transnasal and transoral linear and angled exposure of the CVJ were evaluated by means of X-ray and CT scan in the sagittal plane. RESULTS: The angular difference between the radiological and surgical transoral endoscopic lines was significantly smaller compared with the difference between the radiological and surgical transnasal lines. Finally we found how to calculate preoperatively the "surgical" (effective) Mandibulopalatine line by a simple lateral preoperative radiological study of the CVJ. CONCLUSION: Naso-axial line is confirmed to be a reliable preoperative predictor of the maximal extent of inferior dissection for transnasal approach. Surgical Palatine Inferior dental Arch line will draw the maximal extent of superior dissection for the transoral approach with simple lateral head X-ray examination by open mouth. LEVEL OF EVIDENCE: 3. PMID- 26807817 TI - Influence of Implant Neck Design on Bone Formation Under Mechanical Repetitive Loading: Histomorphometric and Microcomputed Tomographic Studies in Rabbit Tibiae. AB - PURPOSE: The aim of this study was to investigate effects of implant neck design on the original concept of osseointegration and bone formation when applying mechanical repetitive loading by bone-integrated implants. MATERIALS AND METHODS: Twenty-eight anodized Ti-6Al-4V alloy implants with +60 degrees or -60 degrees grooves in the implant neck were placed in the proximal tibial metaphysis of 14 rabbits. Fourteen implants received mechanical repetitive loading along the long axis of the implant for 8 weeks at 12 weeks after implant placement. The remaining 14 implants received no loading. Histomorphometric and microcomputed tomographic analyses were then performed. RESULTS: No effect of neck design was observed without mechanical loading, whereas osseointegration around the +60 degrees grooves was upregulated with mechanical loading. Calculated load effects on bone structure around the implant neck with +60 degrees grooves were larger when compared with the -60 degrees grooves under mechanical loading. CONCLUSIONS: These findings indicate that the establishment of osseointegration and bone formation around the implant neck with +60 degrees grooves is superior to those with -60 degrees grooves under loaded conditions. PMID- 26807816 TI - Real-Time Investigation of Tuberculosis Transmission: Developing the Respiratory Aerosol Sampling Chamber (RASC). AB - Knowledge of the airborne nature of respiratory disease transmission owes much to the pioneering experiments of Wells and Riley over half a century ago. However, the mechanical, physiological, and immunopathological processes which drive the production of infectious aerosols by a diseased host remain poorly understood. Similarly, very little is known about the specific physiological, metabolic and morphological adaptations which enable pathogens such as Mycobacterium tuberculosis (Mtb) to exit the infected host, survive exposure to the external environment during airborne carriage, and adopt a form that is able to enter the respiratory tract of a new host, avoiding innate immune and physical defenses to establish a nascent infection. As a first step towards addressing these fundamental knowledge gaps which are central to any efforts to interrupt disease transmission, we developed and characterized a small personal clean room comprising an array of sampling devices which enable isolation and representative sampling of airborne particles and organic matter from tuberculosis (TB) patients. The complete unit, termed the Respiratory Aerosol Sampling Chamber (RASC), is instrumented to provide real-time information about the particulate output of a single patient, and to capture samples via a suite of particulate impingers, impactors and filters. Applying the RASC in a clinical setting, we demonstrate that a combination of molecular and microbiological assays, as well as imaging by fluorescence and scanning electron microscopy, can be applied to investigate the identity, viability, and morphology of isolated aerosolized particles. Importantly, from a preliminary panel of active TB patients, we observed the real-time production of large numbers of airborne particles including Mtb, as confirmed by microbiological culture and polymerase chain reaction (PCR) genotyping. Moreover, direct imaging of captured samples revealed the presence of multiple rod-like Mtb organisms whose physical dimensions suggested the capacity for travel deep into the alveolar spaces of the human lung. PMID- 26807818 TI - Transmission and Propagation of 'Candidatus Liberibacter asiaticus' by Grafting with Individual Citrus Leaves. AB - Huanglongbing (HLB) is a chronic, progressive decline disease in citrus associated with a systemic infection by the bacterium 'Candidatus Liberibacter asiaticus'. Transmission of the bacterium in the field is by the Asian citrus psyllid, Diaphorina citri Kuwayama. Experimental propagation of 'Ca. L. asiaticus' is done primarily by grafting pieces of bud wood from an infected plant. To produce a small-scale model system for investigation of pathogen biology, we investigated grafting single leaves from infected citrus plants as sources of inoculum for propagation of the bacterium. In total, 162 plants ranging in age from 3 to 18 months were grafted. Grafting with intact asymptomatic and HLB-symptomatic leaves resulted in 61 of 78 (78%) and 35 of 41 (85%) of the plants infected with 'Ca. L. asiaticus', respectively. Inoculum consisting of the leaf petiole only or only an inoculum tissue remnant under the bark of the receptor tree resulted in 6 of 12 (50%) and 7 of 31 (23%) infected trees, respectively. Real-time polymerase chain reaction (qPCR) assays verified the infection in plants, a majority of which developed the foliar blotchy mottle symptom considered diagnostic for HLB, while some plants also displayed the stunted, chlorotic shoots for which the disease is named. The qPCR data together with the symptoms displayed demonstrated that individual leaves from infected trees can serve as effective inoculum sources for transmission and propagation of 'Ca. L. asiaticus' via grafting. PMID- 26807819 TI - Factors Associated With High Levels of Perceived Prenatal Stress Among Inner-City Women. AB - OBJECTIVE: To explore the factors associated with high rates of perceived prenatal stress among inner-city women. DESIGN: Observational cross-sectional study. SETTING/PARTICIPANTS: We conducted a secondary analysis of data from 603 inner-city women. In our study, 330 participants (54.7%) self-identified as First Nations, Metis, or First Nations/Metis. METHODS: Prenatal stress was measured with Cohen's Perceived Stress Scale. A social ecological model provided the theoretical framework for the study, and variables representing all levels of the model were selected for study. Data analyses included t tests to compare women with high stress and low/moderate stress, univariable logistic regression analysis to determine the association of selected factors with maternal stress, and multivariable logistic regression analysis to provide adjusted odds ratios and 95% confidence intervals for the factors. RESULTS: Of the 603 participants, 17.2% (104) reported high levels of perceived stress, and 82.8% (499) reported low/moderate levels. The high-stress group included a significantly greater proportion of First Nations, Metis, or First Nations/Metis women (76.0%) than the low/moderate-stress group (50.3%). Low rates of self-esteem and social support, residential mobility, abuse before/during pregnancy, and experiencing discrimination were significantly associated with high levels of perceived prenatal stress. CONCLUSION: Our findings demonstrated that factors that influence prenatal stress occur at all levels of the social ecological model. The identified factors are amenable to change, and implications for practice include the need for psychosocial risk assessment, alternative forms of prenatal care, relational care, and advocacy initiatives. A greater understanding of the complex factors associated with high rates of perceived prenatal stress can inform the development of effective interventions for inner-city women. PMID- 26807820 TI - Protective Factors, Risk Indicators, and Contraceptive Consistency Among College Women. AB - OBJECTIVE: To explore risk and protective factors associated with consistent contraceptive use among emerging adult female college students and whether effects of risk indicators were moderated by protective factors. DESIGN: Secondary analysis of National Longitudinal Study of Adolescent to Adult Health Wave III data. SETTING: Data collected through in-home interviews in 2001 and 2002. PARTICIPANTS: National sample of 18- to 25-year-old women (N = 842) attending 4-year colleges. METHODS: We examined relationships between protective factors, risk indicators, and consistent contraceptive use. Consistent contraceptive use was defined as use all of the time during intercourse in the past 12 months. Protective factors included external supports of parental closeness and relationship with caring nonparental adult and internal assets of self-esteem, confidence, independence, and life satisfaction. Risk indicators included heavy episodic drinking, marijuana use, and depression symptoms. Multivariable logistic regression models were used to evaluate relationships between protective factors and consistent contraceptive use and between risk indicators and contraceptive use. RESULTS: Self-esteem, confidence, independence, and life satisfaction were significantly associated with more consistent contraceptive use. In a final model including all internal assets, life satisfaction was significantly related to consistent contraceptive use. Marijuana use and depression symptoms were significantly associated with less consistent use. With one exception, protective factors did not moderate relationships between risk indicators and consistent use. CONCLUSION: Based on our findings, we suggest that risk and protective factors may have largely independent influences on consistent contraceptive use among college women. A focus on risk and protective factors may improve contraceptive use rates and thereby reduce unintended pregnancy among college students. PMID- 26807821 TI - Can a GIS toolbox assess the environmental risk of oil spills? Implementation for oil facilities in harbors. AB - Oil spills are one of the most widespread problems in port areas (loading/unloading of bulk liquid, fuel supply). Specific environmental risk analysis procedures for diffuse oil sources that are based on the evolution of oil in the marine environment are needed. Diffuse sources such as oil spills usually present a lack of information, which makes the use of numerical models an arduous and occasionally impossible task. For that reason, a tool that can assess the risk of oil spills in near-shore areas by using Geographical Information System (GIS) is presented. The SPILL Tool provides immediate results by automating the process without miscalculation errors. The tool was developed using the Python and ArcGIS scripting library to build a non-ambiguous geoprocessing workflow. The SPILL Tool was implemented for oil facilities at Tarragona Harbor (NE Spain) and validated showing a satisfactory correspondence (around 0.60 RSR error index) with the results obtained using a 2D calibrated oil transport numerical model. PMID- 26807822 TI - Efficiency evaluation for remediating paddy soil contaminated with cadmium and arsenic using water management, variety screening and foliage dressing technologies. AB - Paddy soils in many regions of China have been seriously polluted by multiple heavy metals or metalloids, such as arsenic (As), cadmium (Cd) and lead (Pb). In order to ensure the safety of food and take full advantage of the limited farmland resources of China, exploring an effective technology to repair contaminated soils is urgent and necessary. In this study, three technologies were employed, including variety screening, water management and foliage dressing, to assess their abilities to reduce the accumulation of Cd and As in the grains of different rice varieties, and meanwhile monitor the related yields. The results of variety screening under insufficient field drying condition showed that the As and Cd contents in the grains of only four varieties [Fengliangyouxiang 1 (P6), Zhongzheyou 8 (P7), Guangliangyou 1128 (P10), Y liangyou 696 (P11)] did not exceed their individual national standard. P6 gained a relatively high grain yield but accumulated less As and Cd in the grains despite of the relatively high As and Cd concentrations in the rhizosphere soil. However, long-playing field drying in water management trial significantly increased Cd but decreased As content in the grains of all tested three varieties including P6, suggesting an important role of water supply in controlling the accumulation of grain As and Cd. Selenium (Se) showed a stronger ability than silicon (Si) to reduce As and Cd accumulation in the grains of Fengliangyou 4 (P2) and Teyou 524 (P13), and keep the yields. The results of this study suggest that combined application of water management and foliage dressing may be an efficient way to control As and Cd accumulation in the grains of paddy rice exposing to As- and Cd-contaminated soils. PMID- 26807824 TI - Thermally Cured Dual Functional Viologen-Based All-in-One Electrochromic Devices with Panchromatic Modulation. AB - Vinyl benzyl viologen (VBV) was synthesized and utilized to obtain all-in-one thermally cured electrochromic devices (ECDs). The vinyl moiety of VBV monomer could react with methyl methacrylate (MMA) to yield bulky VBV/poly(methyl methacrylate) (PMMA) chains and even cross-linked network without the assistance of additional cross-linker. Both the bulky VBV/PMMA chains and the resulting polymer network can hinder the aggregation of the viologens and reduce the possibility of dimerization, rendering enhanced cycling stability. Large transmittance changes (DeltaT) over 60% at both 570 and 615 nm were achieved when the VBV-based ECD was switched from 0 V to a low potential bias of 0.5 V. Ultimately, the dual functional of VBV molecules, serving simultaneously as a promising electrochromic material and a cross-linker, is fully utilized in the proposed electrochromic system, making its fabrication process much easier. Negligible decays in DeltaT at both wavelengths were observed for the cured ECD after being subjected to 1000 repetitive cycles, while 17.1% and 22.0% decays were noticed at 570 and 615 nm, respectively, for the noncured ECD. In addition, the low voltage-driven feature of the VBV-based ECD enables it to be incorporated with phenyl viologen (PV), further expanding the absorption range of the ECD. Panchromatic characteristic of the proposed PV/VBV-based ECD was demonstrated while exhibiting DeltaT over 60% at both wavelengths. Only 5.3% and 6.9% decays, corresponding at 570 and 615 nm, respectively, were observed in the PV/VBV-based ECD after 10 000 continuous cycles at bleaching/coloring voltages of 0/0.5 V with an interval of 10 s for both bleaching and coloring processes. PMID- 26807823 TI - Genetics of Aldosterone-Producing Adenoma in Korean Patients. AB - OBJECTIVES: Recently, somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D genes were found to be associated with the pathogenesis of aldosterone-producing adenoma (APA). This study aimed to investigate the prevalence of somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D and examine the correlations between these mutations and the clinical and biochemical characteristics in Korean patients with APA. METHODS: We performed targeted gene sequencing in 66 patients with APA to detect somatic mutations in these genes. RESULTS: Somatic KCNJ5 mutations were found in 47 (71.2%) of the 66 patients with APA (31 cases of p.G151R and 16 cases of p.L168R); these two mutations were mutually exclusive. Somatic mutations in the ATP1A1, ATP2B3, and CACNA1D genes were not observed. Somatic KCNJ5 mutations were more prevalent in female patients (66% versus 36.8%, respectively; P = 0.030). Moreover, patients with KCNJ5 mutations comprised a significantly higher proportion of patients younger than 35 years of age (19.1% versus 0%, respectively; P = 0.040). There were no significant differences in pre operative blood pressure, plasma aldosterone, serum potassium, lateralization index, and adenoma size according to mutational status. Patients with KCNJ5 mutations were less likely to need antihypertensive medications after adrenalectomy compared with those without mutation (36.2% versus 63.2%; P = 0.045). CONCLUSIONS: The present study demonstrated the high prevalence of somatic KCNJ5 mutations in Korean patients with APA. Carriers of somatic KCNJ5 mutations were more likely to be female. Early diagnosis and better therapeutic outcomes were associated with somatic KCNJ5 mutations in APA. PMID- 26807825 TI - A Comprehensive Study of the Polypropylene Fiber Reinforced Fly Ash Based Geopolymer. AB - As a cementitious material, geopolymers show a high quasi-brittle behavior and a relatively low fracture energy. To overcome such a weakness, incorporation of fibers to a brittle matrix is a well-known technique to enhance the flexural properties. This study comprehensively evaluates the short and long term impacts of different volume percentages of polypropylene fiber (PPF) reinforcement on fly ash based geopolymer composites. Different characteristics of the composite were compared at fresh state by flow measurement and hardened state by variation of shrinkage over time to assess the response of composites under flexural and compressive load conditions. The fiber-matrix interface, fiber surface and toughening mechanisms were assessed using field emission scan electron microscopy (FESEM) and atomic force microscopy (AFM). The results show that incorporation of PPF up to 3 wt % into the geopolymer paste reduces the shrinkage and enhances the energy absorption of the composites. While, it might reduce the ultimate flexural and compressive strength of the material depending on fiber content. PMID- 26807826 TI - Asymmetric Bronsted Base Catalyzed and Directed [3+2] Cycloaddition of 2-Acyl Cycloheptatrienes with Azomethine Ylides. AB - Conjugated cyclic trienes have the potential for different types of cycloaddition reactions. In the present work, we will, in a novel asymmetric cycloaddition reaction, demonstrate that the organocatalytic reaction of 2-acyl cycloheptatrienes with azomethine ylides proceeds as a [3+2] cycloaddition, which is in contrast to the Lewis acid-catalyzed reaction, in which a [3+6] cycloaddition takes place. In the presence of a chiral organosuperbase, 2-acyl cycloheptatrienes react in a highly enantioselective manner in the [3+2] cycloaddition with azomethine ylides, providing the 1,3-dipolar cycloaddition product in high yields and up to 99 % ee. It is also shown that the diene formed by the reaction can undergo stereoselective dihydroxylation, bromination, and cycloaddition reactions. Finally, based on experimental observations, some mechanistic considerations are discussed. PMID- 26807829 TI - Liability issues: Transfer to long-term care. PMID- 26807830 TI - The intersection of policy and informatics. PMID- 26807827 TI - Caspr3-Deficient Mice Exhibit Low Motor Learning during the Early Phase of the Accelerated Rotarod Task. AB - Caspr3 (Contactin-associated protein-like 3, Cntnap3) is a neural cell adhesion molecule belonging to the Caspr family. We have recently shown that Caspr3 is expressed abundantly between the first and second postnatal weeks in the mouse basal ganglia, including the striatum, external segment of the globus pallidus, subthalamic nucleus, and substantia nigra. However, its physiological role remains largely unknown. In this study, we conducted a series of behavioral analyses on Capsr3-knockout (KO) mice and equivalent wild-type (WT) mice to investigate the role of Caspr3 in brain function. No significant differences were observed in most behavioral traits between Caspr3-KO and WT mice, but we found that Caspr3-KO mice performed poorly during the early phase of the accelerated rotarod task in which latency to falling off a rod rotating with increasing velocity was examined. In the late phase, the performance of the Caspr3-KO mice caught up to the level of WT mice, suggesting that the deletion of Caspr3 caused a delay in motor learning. We then examined changes in neural activity after training on the accelerated rotarod by conducting immunohistochemistry using antibody to c-Fos, an indirect marker for neuronal activity. Experience of the accelerated rotarod task caused increases in the number of c-Fos-positive cells in the dorsal striatum, cerebellum, and motor cortex in both Caspr3-KO and WT mice, but the number of c-Fos-positive cells was significantly lower in the dorsal striatum of Caspr3-KO mice than in that of WT mice. The expression of c Fos in the ventral striatum of Caspr3-KO and WT mice was not altered by the training. Our findings suggest that reduced activation of neural cells in the dorsal striatum in Caspr3-KO mice leads to a decline in motor learning in the accelerated rotarod task. PMID- 26807831 TI - Constructing a nursing budget using a patient classification system. PMID- 26807832 TI - Population health: The importance of social determinants. PMID- 26807833 TI - APRN transformational leadership. PMID- 26807834 TI - When seconds matter: Rapid response teams and nurse decision making. PMID- 26807835 TI - A subjective view: Nurse satisfaction and the review process. PMID- 26807837 TI - Peer coaching for nurse managers. PMID- 26807838 TI - Peer interviews: A hiring best practice. PMID- 26807839 TI - Improvements in the method of radiation anomaly detection by spectral comparison ratios. AB - We present a new procedure for configuring the Nuisance-rejection Spectral Comparison Ratio Anomaly Detection (N-SCRAD) method. The procedure minimizes detectable count rates of source spectra at a specified false positive rate using simulated annealing. We also present a new method for correcting the estimates of background variability used in N-SCRAD to current conditions of the total count rate. The correction lowers detection thresholds for a specified false positive rate, enabling greater sensitivity to targets. PMID- 26807840 TI - Hippocampal Context Processing during Acquisition of a Predictive Learning Task Is Associated with Renewal in Extinction Recall. AB - Renewal is defined as the recovery of an extinguished response if extinction and retrieval contexts differ. The context dependency of extinction, as demonstrated by renewal, has important implications for extinction-based therapies. Persons showing renewal (REN) exhibit higher hippocampal activation during extinction in associative learning than those without renewal (NOREN), demonstrating hippocampal context processing, and recruit ventromedial pFC in retrieval. Apart from these findings, brain processes generating renewal remain largely unknown. Conceivably, processing differences in task-relevant brain regions that ultimately lead to renewal may occur already in initial acquisition of associations. Therefore, in two fMRI studies, we investigated overall brain activation and hippocampal activation in REN and NOREN during acquisition of an associative learning task in response to presentation of a context alone or combined with a cue. Results of two studies demonstrated significant activation differences between the groups: In Study 1, a support vector machine classifier correctly assigned participants' brain activation patterns to REN and NOREN groups, respectively. In Study 2, REN and NOREN showed similar hippocampal involvement during context-only presentation, suggesting processing of novelty, whereas overall hippocampal activation to the context-cue compound, suggesting compound encoding, was higher in REN. Positive correlations between hippocampal activation and renewal level indicated more prominent hippocampal processing in REN. Results suggest that hippocampal processing of the context-cue compound rather than of context only during initial learning is related to a subsequent renewal effect. Presumably, REN participants use distinct encoding strategies during acquisition of context-related tasks, which reflect in their brain activation patterns and contribute to a renewal effect. PMID- 26807841 TI - The Semantics of Syntax: The Grounding of Transitive and Intransitive Constructions. AB - Embodied theories of language maintain that brain areas associated with perception and action are also involved in the processing and representation of word meaning. A number of studies have shown that sentences with action verbs elicit activation within sensory-motor brain regions, arguing that sentence induced mental simulations provide a means for grounding their lexical-semantic meaning. Constructionist theories argue, however, that form-meaning correspondence is present not only at the lexical level but also at the level of constructions. We investigated whether sentence-induced motor resonance is present for syntactic constructions. We measured the BOLD signal while participants read sentences with (di)transitive (caused motion) or intransitive constructions that contained either action or abstract verbs. The results showed a distinct neuronal signature for caused motion and intransitive syntactic frames. Caused motion frames activated regions associated with reaching and grasping actions, including the left anterior intraparietal sulcus and the parietal reach region. Intransitive frames activated lateral temporal regions commonly associated with abstract word processing. The left pars orbitalis showed an interaction between the syntactic frame and verb class. These findings show that sensory-motor activation elicited by sentences entails both motor resonance evoked by single words as well as at the level of syntactic constructions. PMID- 26807842 TI - Bilateral Transcranial Direct Current Stimulation Language Treatment Enhances Functional Connectivity in the Left Hemisphere: Preliminary Data from Aphasia. AB - Several studies have already shown that transcranial direct current stimulation (tDCS) is a useful tool for enhancing recovery in aphasia. However, no reports to date have investigated functional connectivity changes on cortical activity because of tDCS language treatment. Here, nine aphasic persons with articulatory disorders underwent an intensive language therapy in two different conditions: bilateral anodic stimulation over the left Broca's area and cathodic contralesional stimulation over the right homologue of Broca's area and a sham condition. The language treatment lasted 3 weeks (Monday to Friday, 15 sessions). In all patients, language measures were collected before (T0) and at the end of treatment (T15). Before and after each treatment condition (real vs. sham), each participant underwent a resting-state fMRI study. Results showed that, after real stimulation, patients exhibited the greatest recovery not only in terms of better accuracy in articulating the treated stimuli but also for untreated items on different tasks of the language test. Moreover, although after the sham condition connectivity changes were confined to the right brain hemisphere, real stimulation yielded to stronger functional connectivity increase in the left hemisphere. In conclusion, our data provide converging evidence from behavioral and functional imaging data that bilateral tDCS determines functional connectivity changes within the lesioned hemisphere, enhancing the language recovery process in stroke patients. PMID- 26807843 TI - Intracellular repair of oxidation-damaged alpha-synuclein fails to target C terminal modification sites. AB - Cellular oxidative stress serves as a common denominator in many neurodegenerative disorders, including Parkinson's disease. Here we use in-cell NMR spectroscopy to study the fate of the oxidation-damaged Parkinson's disease protein alpha-synuclein (alpha-Syn) in non-neuronal and neuronal mammalian cells. Specifically, we deliver methionine-oxidized, isotope-enriched alpha-Syn into cultured cells and follow intracellular protein repair by endogenous enzymes at atomic resolution. We show that N-terminal alpha-Syn methionines Met1 and Met5 are processed in a stepwise manner, with Met5 being exclusively repaired before Met1. By contrast, C-terminal methionines Met116 and Met127 remain oxidized and are not targeted by cellular enzymes. In turn, persisting oxidative damage in the C-terminus of alpha-Syn diminishes phosphorylation of Tyr125 by Fyn kinase, which ablates the necessary priming event for Ser129 modification by CK1. These results establish that oxidative stress can lead to the accumulation of chemically and functionally altered alpha-Syn in cells. PMID- 26807844 TI - Transcriptomic Determinants of Scrapie Prion Propagation in Cultured Ovine Microglia. AB - Susceptibility to infection by prions is highly dependent on the amino acid sequence and host expression of the cellular prion protein (PrPC); however, cellular expression of a genetically susceptible PrPC is insufficient. As an example, it has been shown in cultured cells that permissive and resistant sublines derived from the same parental population often have similar expression levels of PrPC. Thus, additional cellular factors must influence susceptibility to prion infection. The aim of this study was to elucidate the factors associated with relative permissiveness and resistance to scrapie prions in cultured cells derived from a naturally affected species. Two closely related ovine microglia clones with different prion susceptibility, but no detectable differences in PrPC expression levels, were inoculated with either scrapie-positive or scrapie negative sheep brainstem homogenates. Five passages post-inoculation, the transcriptional profiles of mock and infected clones were sequenced using Illumina technology. Comparative transcriptional analyses identified twenty-two differentially transcribed genes, most of which were upregulated in poorly permissive microglia. This included genes encoding for selenoprotein P, endolysosomal proteases, and proteins involved in extracellular matrix remodeling. Furthermore, in highly permissive microglia, transforming growth factor beta-induced, retinoic acid receptor response 1, and phosphoserine aminotranspherase 1 gene transcripts were upregulated. Gene Set Enrichment Analysis identified proteolysis, translation, and mitosis as the most affected pathways and supported the upregulation trend of several genes encoding for intracellular proteases and ribosomal proteins in poorly permissive microglia. This study identifies new genes potentially involved in scrapie prion propagation, corroborates results from other studies, and extends those results into another cell culture model. PMID- 26807845 TI - Post-transcriptional Control of Tumor Cell Autonomous Metastatic Potential by CCR4-NOT Deadenylase CNOT7. AB - Accumulating evidence supports the role of an aberrant transcriptome as a driver of metastatic potential. Deadenylation is a general regulatory node for post transcriptional control by microRNAs and other determinants of RNA stability. Previously, we demonstrated that the CCR4-NOT scaffold component Cnot2 is an inherited metastasis susceptibility gene. In this study, using orthotopic metastasis assays and genetically engineered mouse models, we show that one of the enzymatic subunits of the CCR4-NOT complex, Cnot7, is also a metastasis modifying gene. We demonstrate that higher expression of Cnot7 drives tumor cell autonomous metastatic potential, which requires its deadenylase activity. Furthermore, metastasis promotion by CNOT7 is dependent on interaction with CNOT1 and TOB1. CNOT7 ribonucleoprotein-immunoprecipitation (RIP) and integrated transcriptome wide analyses reveal that CNOT7-regulated transcripts are enriched for a tripartite 3'UTR motif bound by RNA-binding proteins known to complex with CNOT7, TOB1, and CNOT1. Collectively, our data support a model of CNOT7, TOB1, CNOT1, and RNA-binding proteins collectively exerting post-transcriptional control on a metastasis suppressive transcriptional program to drive tumor cell metastasis. PMID- 26807846 TI - Time to diagnosis in young-onset dementia and its determinants: the INSPIRED study. AB - OBJECTIVE: The objective of this study is to identify factors determining the time to diagnosis for young-onset dementia (YOD), defined as dementia with symptom onset before age 65 years, by mapping the diagnostic pathways. METHODS: Participants were recruited via healthcare professionals, community support organisations or were self-referred. Information was obtained by interviews with the person with YOD and their carer, and medical record reviews. Clinical dementia diagnoses were independently ratified by consensus review. RESULTS: Participants included 88 people with YOD (mean age of onset = 55.4 years), due to Alzheimer's disease (AD) (53.4%, n = 47), frontotemporal dementia (FTD) (15.9%, n = 14) and other causes (30.7%, n = 27). Median time from symptom onset to first consultation was 2.3 years, to dementia diagnosis 3.2 years, to family awareness of dementia diagnosis 3.5 years and to final diagnosis of the type of dementia 4.7 years. Non-dementia diagnoses occurred in 48.9%, including depression (30.7%) and mild cognitive impairment (MCI) (17.0%). Participants with younger age of onset had significantly longer time to first consultation and family awareness of the dementia diagnosis. The time to dementia diagnosis was significantly longer when the participant presented with MCI or depression and when the dementia was other than AD or FTD. MCI was associated with significantly longer time to family awareness of dementia diagnosis. CONCLUSIONS: Factors impacting on time to diagnosis vary with the stage of diagnosis in YOD. Longer time to dementia diagnosis occurred in people who were younger at symptom onset, when MCI or depression was present, and in dementias other than AD and FTD. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26807847 TI - Effects of Silicon vs. Hydroxytyrosol-Enriched Restructured Pork on Liver Oxidation Status of Aged Rats Fed High-Saturated/High-Cholesterol Diets. AB - BACKGROUND: Pork is an essential component of the diet that has been linked with major degenerative diseases and development of non-alcoholic steatohepatitis (NASH). Previous studies have. Previous studies have demonstrated the in vitro antioxidant activity of silicon (Si). Furthermore, when Si is added to restructured pork (RP) strongly counterbalances the negative effect of high cholesterol-ingestion, acting as an active hypocholesterolemic and hypolipemic dietary ingredient in aged rats. OBJECTIVE: This study was designed to evaluate the effects of Si vs hydroxytyrosol (HxT) RP on liver antioxidant defense in aged rats fed cholesterol-enriched high saturated/high cholesterol diets as a NASH model. METHODS: Four diets were prepared: Control RP diet (C) with non-added cholesterol; Cholesterol-enriched high-saturated/high-cholesterol control RP diet (CHOL-C) with added cholesterol and cholic acid; Si- or HxT-RP cholesterol enriched high-saturated/high-cholesterol diets (CHOL-Si and CHOL-HxT). Groups of six male Wistar rats (1-yr old) were fed these modified diets for eight weeks. Total cholesterol, hepatosomatic index, liver Nrf2 and antioxidant (CAT, SOD, GSH, GSSG, GR, GPx) markers were determined. RESULTS: Both CHOL-Si and CHOL-HxT diets enhanced the liver antioxidant status, reduced hepatosomatic index and increased SOD actvity. Hydrogen peroxide removal seemed to be involved, explaining that the value of redox index was even lower than C without changing the CAT activity. CHOL-Si results were quite better than CHOL-HxT in most measured parameters. CONCLUSIONS: Our study suggests that Si incorporated into RP matrix was able to counterbalance, more efficiently than HxT, the deleterious effect of consuming a high-saturated/high-cholesterol diet, by improving the liver antioxidant defenses in the context of NASH. PMID- 26807848 TI - Sustainability in Supply Chain Management: Aggregate Planning from Sustainability Perspective. AB - Supply chain management that considers the flow of raw materials, products and information has become a focal issue in modern manufacturing and service systems. Supply chain management requires effective use of assets and information that has far reaching implications beyond satisfaction of customer demand, flow of goods, services or capital. Aggregate planning, a fundamental decision model in supply chain management, refers to the determination of production, inventory, capacity and labor usage levels in the medium term. Traditionally standard mathematical programming formulation is used to devise the aggregate plan so as to minimize the total cost of operations. However, this formulation is purely an economic model that does not include sustainability considerations. In this study, we revise the standard aggregate planning formulation to account for additional environmental and social criteria to incorporate triple bottom line consideration of sustainability. We show how these additional criteria can be appended to traditional cost accounting in order to address sustainability in aggregate planning. We analyze the revised models and interpret the results on a case study from real life that would be insightful for decision makers. PMID- 26807849 TI - Zfrp8/PDCD2 Interacts with RpS2 Connecting Ribosome Maturation and Gene-Specific Translation. AB - Zfrp8/PDCD2 is a highly conserved protein essential for stem cell maintenance in both flies and mammals. It is also required in fast proliferating cells such as cancer cells. Our previous studies suggested that Zfrp8 functions in the formation of mRNP (mRNA ribonucleoprotein) complexes and also controls RNA of select Transposable Elements (TEs). Here we show that in Zfrp8/PDCD2 knock down (KD) ovaries, specific mRNAs and TE transcripts show increased nuclear accumulation. We also show that Zfrp8/PDCD2 interacts with the (40S) small ribosomal subunit through direct interaction with RpS2 (uS5). By studying the distribution of endogenous and transgenic fluorescently tagged ribosomal proteins we demonstrate that Zfrp8/PDCD2 regulates the cytoplasmic levels of components of the small (40S) ribosomal subunit, but does not control nuclear/nucleolar localization of ribosomal proteins. Our results suggest that Zfrp8/PDCD2 functions at late stages of ribosome assembly and may regulate the binding of specific mRNA-RNPs to the small ribosomal subunit ultimately controlling their cytoplasmic localization and translation. PMID- 26807851 TI - A 3,7-Dihydroxyphenoxazine-based Fluorescent Probe for Selective Detection of Intracellular Hydrogen Peroxide. AB - A novel N-borylbenzyloxycarbonyl-3,7-dihydroxyphenoxazine fluorescent probe (NBCD) for detecting H2O2 in living cells is described. The probe could achieve high selectivity for detecting H2O2 over other biological reactive oxygen species (ROS). In addition, upon addition of H2O2, NBCD exhibited color change from colorless to pink, which makes it a "naked-eye" probe for H2O2 detection. NBCD could not only be used to detect enzymatically generated H2O2 but also to detect H2O2 in living systems by using fluorescence spectroscopy, with a detection limit of 2 MUm. Importantly, NBCD enabled the visualization of epidermal growth factor (EGF)-stimulated H2O2 generation inside the cells. PMID- 26807850 TI - Visual Cross-Modal Re-Organization in Children with Cochlear Implants. AB - BACKGROUND: Visual cross-modal re-organization is a neurophysiological process that occurs in deafness. The intact sensory modality of vision recruits cortical areas from the deprived sensory modality of audition. Such compensatory plasticity is documented in deaf adults and animals, and is related to deficits in speech perception performance in cochlear-implanted adults. However, it is unclear whether visual cross-modal re-organization takes place in cochlear implanted children and whether it may be a source of variability contributing to speech and language outcomes. Thus, the aim of this study was to determine if visual cross-modal re-organization occurs in cochlear-implanted children, and whether it is related to deficits in speech perception performance. METHODS: Visual evoked potentials (VEPs) were recorded via high-density EEG in 41 normal hearing children and 14 cochlear-implanted children, aged 5-15 years, in response to apparent motion and form change. Comparisons of VEP amplitude and latency, as well as source localization results, were conducted between the groups in order to view evidence of visual cross-modal re-organization. Finally, speech perception in background noise performance was correlated to the visual response in the implanted children. RESULTS: Distinct VEP morphological patterns were observed in both the normal hearing and cochlear-implanted children. However, the cochlear-implanted children demonstrated larger VEP amplitudes and earlier latency, concurrent with activation of right temporal cortex including auditory regions, suggestive of visual cross-modal re-organization. The VEP N1 latency was negatively related to speech perception in background noise for children with cochlear implants. CONCLUSION: Our results are among the first to describe cross modal re-organization of auditory cortex by the visual modality in deaf children fitted with cochlear implants. Our findings suggest that, as a group, children with cochlear implants show evidence of visual cross-modal recruitment, which may be a contributing source of variability in speech perception outcomes with their implant. PMID- 26807852 TI - The Effect of Laser Trabeculoplasty on Posture-Induced Intraocular Pressure Changes in Patients with Open Angle Glaucoma. AB - PURPOSE: To investigate the effect of argon laser trabeculoplasty (ALT) on posture-induced intraocular pressure (IOP) changes in patients with open angle glaucoma (OAG). METHODS: Thirty eyes of 30 consecutive patients with OAG who underwent ALT were prospectively analyzed. The IOP was measured using Icare PRO in the sitting position, supine position, and dependent lateral decubitus position (DLDP) before ALT and at 1 week, 1 month, 2 months, and 3 months after ALT. RESULTS: Compared to the baseline values, the IOP in each position was significantly decreased after ALT (all P < 0.001). During follow-up, the mean percentage of IOP reduction was similar in the sitting and supine positions, but was significantly lower in DLDP than in the sitting or supine positions (all P < 0.05). In terms of postural IOP changes, the IOP in the supine position and DLDP was significantly higher than that in the sitting position at the same time points during the follow-up period (all P < 0.001). The difference between the IOP in the supine position and DLDP during follow-up was significant (all P < 0.001). The extent of IOP differences between any positions did not show significant changes during the follow-up period (all P > 0.05). CONCLUSIONS: ALT appears to be effective in lowering the IOP in various body positions, but the degree of this effect was significantly lower in DLDP. In addition, ALT seemed to have limited effects on posture-induced IOP changes. PMID- 26807853 TI - Improving COPD Care in a Medically Underserved Primary Care Clinic: A Qualitative Study of Patient Perspectives. AB - We conducted a focus group study in an urban hospital-based primary care teaching clinic serving an indigent and Hispanic (predominantly Puerto Rican) population in New England in order to learn how patients with Chronic Obstructive Lung Disease (COPD) perceive their disease, how they experience their medical care, and the barriers they face managing their disease and following medical recommendations. The research team included medical doctors, nurses, a medical anthropologist, a clinical pharmacist, a hospital interpreter, and a systems analyst. Four focus groups were conducted in Spanish and English in April and May 2014. The demographic characteristics of the 25 focus group participants closely reflected the demographics of the total COPD clinic patients. The participants were predominantly female (72%) and Hispanic (72%) and had a median age of 63. The major themes expressed in the focus groups included: problems living with COPD; coping with complexities of comorbid illnesses; challenges of quitting smoking and maintaining cessation; dealing with second-hand smoke; beliefs and myths about quitting smoking; difficulty paying for and obtaining medications; positive experiences obtaining and managing medications; difficulties in using sleep machines at home; expressions of disappointment with the departure of their doctors; and overall satisfaction with the clinic health care providers. The study led to the creation of an action plan that addresses the concerns expressed by the focus study participants. The action plan is spearheaded by a designated bilingual and bicultural nurse and is now in operation. PMID- 26807854 TI - Treatment of cT1a Renal Tumours in Germany: A Nationwide Survey. AB - OBJECTIVE: To identify clinical parameters influencing German urologists treating cT1a renal tumours, we performed a nationwide survey among members of the German urological associations (DGU and BDU). MATERIAL AND METHODS: In spring 2012, DGU and BDU members were invited to complete our survey. For 8 cases and 3 index patients, participants were asked about their preferred treatment. Multivariate analyses were used to identify significant parameters leading the responders to favour radical nephrectomy (RN) over nephron sparing surgery (NSS) as well as active surveillance (AS) over invasive treatment. RESULTS: Three hundred six (7.4%) forms were included in our analysis. In patients with larger tumours (4 vs. 2 cm, OR 3.16), endophytic growth (endophytic vs. exophytic, OR 2.70), hilar tumour location (perihilar vs. polar, OR 14.37), normal renal function (normal vs. decreased, OR 1.92) and elderly patients (elderly vs. young, OR 2.14) RN was preferred. Based on decreased renal function (decreased vs. normal, OR 12.74), elderly (elderly vs. young, OR 14.31) and hilar tumour location (perihilar vs. polar, OR 2.14), 77.2% of respondents recommended AS for selected patients. Treating physician factors had no influence on the treatment preference. CONCLUSIONS: Elderly patients with small tumours and impaired renal function were candidates for AS. Younger patients mainly underwent NSS. However, when the tumours' location was endophytic or hilar, RN was recommended. PMID- 26807856 TI - Do Diagnostic Criteria for Psychosomatic Research Explain Diagnosis of Medically Unexplained Somatic Symptoms. PMID- 26807855 TI - Effect of birth weight on adulthood renal function: A bias-adjusted meta-analytic approach. AB - While the association between low birth weight (LBW; <2500 g) and development of adult chronic renal disease (CKD) is inconsistently reported, less information is available regarding association of high birth weight (HBW; >=4000 g) with CKD. We undertook a systematic review and meta-analysis on studies published before 30 September 2015 and report associations between birth weight and renal function. Blood (glomerular filtration rate (GFR)) and urine (microalbuminuria/albumin excreation rate (AER)/urinary albumin creatinine ratio (ACR)) parameters were used to define CKD. Three different effect size estimates were used (odds ratio, regression coefficient and mean difference). The odds of developing CKD in the life course among those born LBW was 1.77 (95% CI: 1.42, 2.20) times and 1.68 (1.27, 2.33) times, assessed by blood and urine parameters respectively. Higher risk was also observed among Asian and Australian populations (blood: OR 2.68; urine: OR 2.28), individuals aged <=30 years (blood: OR 2.30; urine: OR 1.26), and >=50 years (blood: OR 3.66; urine: OR 3.10), people with diabetes (blood: OR 2.51), and aborigines (urine: OR 2.32). There was no significant association between HBW and CKD. For every 1 kg increase in BW, the estimated GFR increased by 2.09 mL/min per 1.73 m(2) (1.33-2.85), and it was negatively associated with LogACR (beta -0.07, 95% CI: -0.14, 0.00). LBW inborn had lower mean GFR -4.62 ( 7.10, -2.14) compared with normal BW. Findings of this study suggest that LBW increased the risk of developing CKD, and HBW did not show any significant impact. PMID- 26807857 TI - Chemotherapy Agents Alter Plasma Lipids in Breast Cancer Patients and Show Differential Effects on Lipid Metabolism Genes in Liver Cells. AB - Cardiovascular complications have emerged as a major concern for cancer patients. Many chemotherapy agents are cardiotoxic and some appear to also alter lipid profiles, although the mechanism for this is unknown. We studied plasma lipid levels in 12 breast cancer patients throughout their chemotherapy. Patients received either four cycles of doxorubicin and cyclophosphamide followed by weekly paclitaxel or three cycles of epirubicin, cyclophosphamide and 5' fluorouracil followed by three cycles of docetaxel. Patients demonstrated a significant reduction (0.32 mmol/L) in high density lipoprotein cholesterol (HDL C) and apolipoprotein A1 (apoA1) levels (0.18 g/L) and an elevation in apolipoprotein B (apoB) levels (0.15 g/L) after treatment. Investigation of the individual chemotherapy agents for their effect on genes involved in lipoprotein metabolism in liver cells showed that doxorubicin decreased ATP binding cassette transporter A1 (ABCA1) via a downregulation of the peroxisomal proliferator activated receptor gamma (PPARgamma) and liver X receptor alpha (LXRalpha) transcription factors. In contrast, ABCA1 levels were not affected by cyclophosphamide or paclitaxel. Likewise, apoA1 levels were reduced by doxorubicin and remained unaffected by cyclophosphamide and paclitaxel. Doxorubicin and paclitaxel both increased apoB protein levels and paclitaxel also decreased low density lipoprotein receptor (LDLR) protein levels. These findings correlate with the observed reduction in HDL-C and apoA1 and increase in apoB levels seen in these patients. The unfavourable lipid profiles produced by some chemotherapy agents may be detrimental in the longer term to cancer patients, especially those already at risk of cardiovascular disease (CVD). This knowledge may be useful in tailoring effective follow-up care plans for cancer survivors. PMID- 26807858 TI - Intralimb Coordination Patterns in Absent, Mild, and Severe Stages of Diabetic Neuropathy: Looking Beyond Kinematic Analysis of Gait Cycle. AB - AIM: Diabetes Mellitus progressively leads to impairments in stability and joint motion and might affect coordination patterns, mainly due to neuropathy. This study aims to describe changes in intralimb joint coordination in healthy individuals and patients with absent, mild and, severe stages of neuropathy. METHODS: Forty-seven diabetic patients were classified into three groups of neuropathic severity by a fuzzy model: 18 without neuropathy (DIAB), 7 with mild neuropathy (MILD), and 22 with moderate to severe neuropathy (SVRE). Thirteen healthy subjects were included as controls (CTRL). Continuous relative phase (CRP) was calculated at each instant of the gait cycle for each pair of lower limb joints. Analysis of Variance compared each frame of the CRP time series and its standard deviation among groups (alpha = 5%). RESULTS: For the ankle-hip CRP, the SVRE group presented increased variability at the propulsion phase and a distinct pattern at the propulsion and initial swing phases compared to the DIAB and CTRL groups. For the ankle-knee CRP, the 3 diabetic groups presented more anti-phase ratios than the CTRL group at the midstance, propulsion, and terminal swing phases, with decreased variability at the early stance phase. For the knee hip CRP, the MILD group showed more in-phase ratio at the early stance and terminal swing phases and lower variability compared to all other groups. All diabetic groups were more in-phase at early the midstance phase (with lower variability) than the control group. CONCLUSION: The low variability and coordination differences of the MILD group showed that gait coordination might be altered not only when frank evidence of neuropathy is present, but also when neuropathy is still incipient. The ankle-knee CRP at the initial swing phase showed distinct patterns for groups from all degrees of neuropathic severity and CTRLs. The ankle-hip CRP pattern distinguished the SVRE patients from other diabetic groups, particularly in the transitional phase from stance to swing. PMID- 26807859 TI - TLR2-Modulating Lipoproteins of the Mycobacterium tuberculosis Complex Enhance the HIV Infectivity of CD4+ T Cells. AB - Co-infection with Mycobacterium tuberculosis accelerates progression from HIV to AIDS. Our previous studies showed that M. tuberculosis complex, unlike M. smegmatis, enhances TLR2-dependent susceptibility of CD4+ T cells to HIV. The M. tuberculosis complex produces multiple TLR2-stimulating lipoproteins, which are absent in M. smegmatis. M. tuberculosis production of mature lipoproteins and TLR2 stimulation is dependent on cleavage by lipoprotein signal peptidase A (LspA). In order to determine the role of potential TLR2-stimulating lipoproteins on mycobacterial-mediated HIV infectivity of CD4+ T cells, we generated M. smegmatis recombinant strains overexpressing genes encoding various M. bovis BCG lipoproteins, as well as a Mycobacterium bovis BCG strain deficient in LspA (DeltalspA). Exposure of human peripheral blood mononuclear cells (PBMC) to M. smegmatis strains overexpressing the BCG lipoproteins, LprF (p<0.01), LprH (p<0.05), LprI (p<0.05), LprP (p<0.001), LprQ (p<0.005), MPT83 (p<0.005), or PhoS1 (p<0.05), resulted in increased HIV infectivity of CD4+ T cells isolated from these PBMC. Conversely, infection of PBMC with DeltalspA reduced HIV infectivity of CD4+ T cells by 40% relative to BCG-infected cells (p<0.05). These results may have important implications for TB vaccination programs in areas with high mother-to-child HIV transmission. PMID- 26807860 TI - Titanium deposition from ionic liquids - appropriate choice of electrolyte and precursor. AB - In this study titanium isopropoxide was dissolved in 1-butyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)imide (BMITFSI) and further in a custom-made guanidinium-based ionic liquid (N11N11NpipGuaTFSI). Electrochemical investigations were carried out by means of cyclic voltammetry (CV) and the initial stages of metal deposition were followed by in situ scanning tunneling microscopy (STM). For BMITFSI we found one large cathodic reduction peak at a potential of -1.2 V vs. Pt, corresponding to the growth of monoatomic high islands. The obtained deposit was identified as elemental titanium by Auger Electron Spectroscopy (AES). Furthermore, we found a corresponding anodic peak at -0.3 V vs. Pt, which is associated with the dissolution of the islands. This observation leads to the assumption that titanium deposition from the imidazolium based room-temperature ionic liquid (RTIL) proceeds in a one-step electron transfer. In contrast, for the guanidinium-based RTIL we found several peaks during titanium reduction and oxidation, which indicates a multi-step electron transfer in this alternative electrolyte. PMID- 26807861 TI - Discovery of Dual Inhibitors for Wild Type and D816V Mutant of c-KIT Kinase through Virtual and Biochemical Screening of Natural Products. AB - Although stem cell factor receptor (c-KIT) kinase is responsible for various malignant human cancers, the presence of constitutively active gain-of-function mutants has made it difficult to discover new anticancer agents using c-KIT as the target protein. To identify the common inhibitors of wild-type c-KIT and the most abundant gain-of-function mutant (D816V), the virtual screening of natural products was performed for the two target proteins in parallel with the scoring function improved by implementing a sophisticated solvation free energy term. As a result, four common inhibitors of natural origin are found with biochemical potencies ranging from low micromolar to submicromolar levels. The results of extensive docking simulations show that although the natural-product inhibitors establish weaker hydrophobic interactions with the D816V mutant than with the wild type, they exhibit a little higher inhibitory activity for the former than the latter by strengthening the hydrogen-bond interactions to a sufficient extent. Of the four natural-product inhibitors, (Z)-6-hydroxy-2-(4 methoxybenzylidene)benzofuran-3(2H)-one (3) is anticipated to serve as a new molecular core for the structure-activity relationship studies to optimize the biochemical potencies because it exhibits good inhibitory activity against both the wild type and D816V mutant despite its low molecular weight (268.3 amu). PMID- 26807862 TI - SMAD7 prevents heterotopic ossification in a rat Achilles tendon injury model via regulation of endothelial-mesenchymal transition. AB - The endothelial-mesenchymal transition (EndMT) is known to play a central role in the pathological process of heterotopic ossification (HO). Based on the ability of SMAD7 (mothers against decapentaplegic homolog 7) to block EndMT-related processes such as myofibroblast transformation, we hypothesized that SMAD7 may be a potential therapeutic target for HO. We constructed a lentivirus overexpressing SMAD7 and tested on rat aortic endothelial cells for optimal titre and transduction efficiency. The lentivirus was then injected into a surgical rat model of Achilles tendon injury. Expression of endothelial markers and mesenchymal markers at the injury sites was subsequently quantified by qPCR and western analysis. Lentiviral delivery of SMAD7 in vivo resulted in an upregulation of endothelial markers (CD31, VE-cadherin) and a downregulation of mesenchymal markers (N-cadherin and vimentin), suggesting that EndMT is blocked due to local SMAD7 overexpression. The difference is more apparent at 10 weeks than at 6 weeks after surgery. X-ray imaging and histological staining further confirmed the absence of ossified structure in the tendon tissue injected with SMAD7-delivering lentivirus, as opposed to the control groups. Post-surgical HO may be prevented in vivo by local delivery of SMAD7 without affecting the normal wound-healing process. These data advance our understanding of the HO process at the molecular level, and provide additional avenues for the prevention and treatment of postoperative HO. PMID- 26807863 TI - PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways inhibitors as anticancer agents: Structural and pharmacological perspectives. AB - The protein kinases regulate cellular functions such as transcription, translation, proliferation, growth and survival by the process of phosphorylation. Over activation of signaling pathways play a major role in oncogenesis. The PI3K signaling pathway is dysregulated almost in all cancers due to the amplification, genetic mutation of PI3K gene and the components of the PI3K pathway themselves. Stimulation of the PI3K/Akt/mTOR and Ras/Raf/MEK/ERK pathways enhances growth, survival, and metabolism of cancer cells. Recently, the PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways have been identified as promising therapeutic targets for cancer therapy. The kinase inhibitors with enhanced specificity and improved pharmacokinetics have been considered for design and development of anticancer agents. This review focuses primarily on the Ras/Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways as therapeutic targets of anticancer drugs, their specific and dual inhibitors, structure activity relationships (SARs) and inhibitors under clinical trials. PMID- 26807864 TI - Inhibition of tau aggregation using a naturally-occurring cyclic peptide scaffold. AB - Disulfide-rich macrocyclic peptides are emerging as versatile scaffolds for the development of stable biochemical tools. This potential is due to the combination of their structural stability and range of bioactivities. Here, we explored the activity of these peptides on fibril growth of the hexapeptide Ac-VQIVYK-NH2 (AcPHF6), which is a tau-derived peptide that has been widely used to understand the pathological mechanism of numerous tauopathies, including Alzheimer's disease. Of the cyclic peptides tested, SFTI-1 and kB1 showed an inherent ability to inhibit AcPHF6 fibril formation. Using an end-capping strategy and combining it with a molecular grafting approach, we demonstrated that SFTI-1 could be used as a starting point to design more potent fibril inhibitors. We further identified chemical and structural features of SFTI-1 and its analogues that underpin their inhibitory activity. The ability to inhibit fibril growth using the strategy employed herein supports the 'steric zipper' model of AcPHF6 fibril formation and shows that naturally-occurring cyclic peptides have potential as drug leads or molecular probes for understanding fibril formation. PMID- 26807865 TI - Induction of targeted osteogenesis with 3-aryl-2H-benzopyrans and 3-aryl-3H benzopyrans: Novel osteogenic agents. AB - Development of target oriented chemotherapeutics for treatment of chronic diseases have been considered as an important approach in drug development. Following this approach, in our efforts for exploration of new osteogenic leads, substituted 3-aryl-2H-benzopyran and 3-aryl-3H-benzopyran derivatives (19, 20a-e, 21, 22a-e, 26, 27, 28a-e, 29, 31a-b, 32 and 33) have been characterized as estrogen receptor-beta selective osteogenic (bone forming) agents. The synthesized compounds were evaluated for osteogenic activity using mouse calvarial osteoblast cells. Four compounds viz20b, 22a, 27and 32 showed significant osteogenic activity at EC50 values 1.35, 34.5, 407 and 29.5pM respectively. Out of these, 20b and 32 were analyzed for their bone mineralization efficacy and osteogenic gene expression by qPCR. The results showed that 20b and 32 significantly increased mineral nodule formation and the transcript levels of BMP-2, RUNX-2 and osteocalcin at 100pM concentrations respectively. Further mechanistic studies of 20b and 32 using transiently knocked down expression of ER-alpha and beta in mouse osteoblast (MOBs) showed that 20b and 32 exerts osteogenic efficacy via activation of estrogen receptor-beta preferentially. Additionally, compounds showed significant anticancer activity in a panel of cancer cell lines within the range of (IC50) 6.54-27.79MUM. The most active molecule, 22b inhibited proliferation of cells by inducing apoptosis and arresting cell cycle at sub-G0 phase with concomitant decrease in cells at S phase. PMID- 26807866 TI - Disruption of steroidogenesis: Cell models for mechanistic investigations and as screening tools. AB - In the modern world, humans are exposed during their whole life to a large number of synthetic chemicals. Some of these chemicals have the potential to disrupt endocrine functions and contribute to the development and/or progression of major diseases. Every year approximately 1000 novel chemicals, used in industrial production, agriculture, consumer products or as pharmaceuticals, are reaching the market, often with limited safety assessment regarding potential endocrine activities. Steroids are essential endocrine hormones, and the importance of the steroidogenesis pathway as a target for endocrine disrupting chemicals (EDCs) has been recognized by leading scientists and authorities. Cell lines have a prominent role in the initial stages of toxicity assessment, i.e. for mechanistic investigations and for the medium to high throughput analysis of chemicals for potential steroidogenesis disrupting activities. Nevertheless, the users have to be aware of the limitations of the existing cell models in order to apply them properly, and there is a great demand for improved cell-based testing systems and protocols. This review intends to provide an overview of the available cell lines for studying effects of chemicals on gonadal and adrenal steroidogenesis, their use and limitations, as well as the need for future improvements of cell-based testing systems and protocols. PMID- 26807867 TI - WITHDRAWN: The combination of tacrolimus and entecavir improves the remission of HBV-associated glomerulonephritis without enhancing viral replication. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 26807869 TI - Wear study of Total Ankle Replacement explants by microstructural analysis. AB - The implantation of Total Ankle Replacement (TAR) prostheses generally gives satisfactory results. However, a high revision rate is associated with the Ankle Evolutive System (AES) implant, due to periprosthetic osteolysis that generates significant cortical lesions and bone cysts in the periprosthetic region. Radioclinical and histological analyses of peri-implant tissues show the presence of numerous foreign particles that may come from the implant. It is known that a precocious wear of materials may lead to an important rate of foreign body in tissues and may generate osteolysis lesions and inflammatory reactions. Thus the objectives of this retrospective study of 10 AES TAR implants (recovered after revision surgeries) are to understand how the prostheses wear out, which part is the most stressed and to determine the nature and size of foreign body particles. A better understanding of friction mechanisms between the three parts of the implant and of the nature and morphology of foreign particles generated was needed to explain the in vivo behavior of the implant. This was achieved using microstuctural and tomographic analysis of both implants parts and periprosthetic tissues. PMID- 26807868 TI - Evaluation of an Algorithm to Predict Menstrual-Cycle Phase at the Time of Injury. AB - CONTEXT: Women are 2 to 8 times more likely to sustain an anterior cruciate ligament (ACL) injury than men, and previous studies indicated an increased risk for injury during the preovulatory phase of the menstrual cycle (MC). However, investigations of risk rely on retrospective classification of MC phase, and no tools for this have been validated. OBJECTIVE: To evaluate the accuracy of an algorithm for retrospectively classifying MC phase at the time of a mock injury based on MC history and salivary progesterone (P4) concentration. DESIGN: Descriptive laboratory study. SETTING: Research laboratory. PARTICIPANTS: Thirty one healthy female collegiate athletes (age range, 18-24 years) provided serum or saliva (or both) samples at 8 visits over 1 complete MC. MAIN OUTCOME MEASURE(S): Self-reported MC information was obtained on a randomized date (1-45 days) after mock injury, which is the typical timeframe in which researchers have access to ACL-injured study participants. The MC phase was classified using the algorithm as applied in a stand-alone computational fashion and also by 4 clinical experts using the algorithm and additional subjective hormonal history information to help inform their decision. To assess algorithm accuracy, phase classifications were compared with the actual MC phase at the time of mock injury (ascertained using urinary luteinizing hormone tests and serial serum P4 samples). Clinical expert and computed classifications were compared using kappa statistics. RESULTS: Fourteen participants (45%) experienced anovulatory cycles. The algorithm correctly classified MC phase for 23 participants (74%): 22 (76%) of 29 who were preovulatory/anovulatory and 1 (50%) of 2 who were postovulatory. Agreement between expert and algorithm classifications ranged from 80.6% (kappa = 0.50) to 93% (kappa = 0.83). Classifications based on same-day saliva sample and optimal P4 threshold were the same as those based on MC history alone (87.1% correct). Algorithm accuracy varied during the MC but at no time were both sensitivity and specificity levels acceptable. CONCLUSIONS: These findings raise concerns about the accuracy of previous retrospective MC-phase classification systems, particularly in a population with a high occurrence of anovulatory cycles. PMID- 26807870 TI - An update on the comorbidity of ADHD and ASD: a focus on clinical management. AB - Attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) commonly co-occur. With the DSM-5, clinicians are permitted to make an ASD diagnosis in the context of ADHD. In earlier versions of the DSM, this was not acceptable. Both ASD and ADHD are reported to have had substantial increases in prevalence within the past 10 years. As a function of both the increased prevalence of both disorders as well as the ability to make an ASD diagnosis in ADHD, there has been a significant amount of research focusing on the comorbidity between ADHD and ASD in the past few years. Here, we provide an update on the biological, cognitive and behavioral overlap/distinctiveness between the two neurodevelopmental disorders with a focus on data published in the last four years. Treatment strategies for the comorbid condition as well as future areas of research and clinical need are discussed. PMID- 26807871 TI - Correction to "Freeing" Graphene from Its Substrate: Observing Intrinsic Velocity Saturation with Rapid Electrical Pulsing. PMID- 26807872 TI - [In Process Citation]. PMID- 26807873 TI - Strategies Used by Prehospital Providers to Overcome Language Barriers. AB - OBJECTIVE: Language barriers are commonly encountered in the prehospital setting but there is a paucity of research on how prehospital providers address language discordance. We sought to identify the communication strategies, and the limitations of those strategies, used by emergency medical services (EMS) providers when confronted with language barriers in a variety of linguistic and cultural contexts. METHODS: EMS providers were queried regarding communication strategies to overcome language barriers as part of an international, multi-site, sequential explanatory, qualitative-predominant, mixed methods study of prehospital language barriers. A survey of EMS telecommunicators was administered at dispatch centers in New Mexico (United States) and Western Cape (South Africa). Semi-structured qualitative interviews of EMS field providers were conducted at agencies who respond to calls from participating dispatch centers. Survey data included quantitative data on demographics and communication strategies used to overcome language barriers as well as qualitative free-text responses on the limitations of strategies. Interviews elicited narratives of encounters with language-discordant patients and the strategies used to communicate. Data from the surveys and interviews were integrated at the point of analysis. RESULTS: 125 telecommunicators (overall response rate of 84.5%) and a purposive sample of 27 field providers participated in the study. The characteristics of participants varied between countries and between agencies, consistent with variations in participating agencies' hiring and training practices. Telecommunicators identified 3rd-party telephonic interpreter services as the single most effective strategy when available, but also described time delays and frustration with interpreter communications that leads them to preferentially try other strategies. In the field, all providers reported using similar strategies, relying heavily on bystanders, multilingual coworkers, and non-verbal communication. Prehospital providers described significant limitations to these strategies, including time delays, breaches of patient confidentiality, and inaccurate interpretation. Participants suggested various resources to improve communication with language-discordant patients. CONCLUSIONS: Prehospital providers rely upon similar, informal strategies for overcoming language barriers across a variety of locations, provider types, and linguistic and cultural contexts. PMID- 26807875 TI - Modulating macrophage polarization with divalent cations in nanostructured titanium implant surfaces. AB - Nanoscale topographical modification and surface chemistry alteration using bioactive ions are centrally important processes in the current design of the surface of titanium (Ti) bone implants with enhanced bone healing capacity. Macrophages play a central role in the early tissue healing stage and their activity in response to the implant surface is known to affect the subsequent healing outcome. Thus, the positive modulation of macrophage phenotype polarization (i.e. towards the regenerative M2 rather than the inflammatory M1 phenotype) with a modified surface is essential for the osteogenesis funtion of Ti bone implants. However, relatively few advances have been made in terms of modulating the macrophage-centered early healing capacity in the surface design of Ti bone implants for the two important surface properties of nanotopography and and bioactive ion chemistry. We investigated whether surface bioactive ion modification exerts a definite beneficial effect on inducing regenerative M2 macrophage polarization when combined with the surface nanotopography of Ti. Our results indicate that nanoscale topographical modification and surface bioactive ion chemistry can positively modulate the macrophage phenotype in a Ti implant surface. To the best of our knowledge, this is the first demonstration that chemical surface modification using divalent cations (Ca and Sr) dramatically induces the regenerative M2 macrophage phenotype of J774.A1 cells in nanostructured Ti surfaces. In this study, divalent cation chemistry regulated the cell shape of adherent macrophages and markedly up-regulated M2 macrophage phenotype expression when combined with the nanostructured Ti surface. These results provide insight into the surface engineering of future Ti bone implants that are harmonized between the macrophage-governed early wound healing process and subsequent mesenchymal stem cell-centered osteogenesis function. PMID- 26807876 TI - Emerging drugs for psoriatic arthritis. AB - INTRODUCTION: The majority of Psoriatic Arthritis patients experience a good clinical response to anti-Tumor Necrosis Factor (TNF)-alpha therapies. However, treatment failure with anti-TNF-alpha can represent a relevant clinical problem. AREAS COVERED: We review the efficacy and safety profile of biological therapies that have been reported from randomized, controlled trials in phase II and phase III available in Pubmed Database for agents targeting IL-12/23p40 antibody (ustekinumab) and IL-17 (secukinumab), inhibitor of phosphodiesterase 4, (apremilast), and of JAK/STAT pathways (tofacitinib) and CTLA4 co-stimulation (abatacept) in Psoriatic Arthritis. EXPERT OPINION: In Psoriatic Arthritis, main emerging drugs are represented by the fully human monoclonal IL-12/23p40 antibody, ustekinumab, the agent targeting IL-17, secukinumab, and the inhibitor of phosphodiesterase 4, apremilast. Results on T cell co-stimulation inhibition by abatacept are insufficient both in psoriasis and in PsA. In vitro investigations on JAK/STAT pathways in PsA suggest that tofacitinib could represent a further valuable therapeutic option. Emerging biological treatments other than anti-TNF agents, ustekinumab, secukinumab and apremilast appear promising for Psoriatic Arthritis and recent studies have showed a good efficacy and an acceptable safety profile; however, further and long-term studies are advocated. PMID- 26807874 TI - The Role of Alpha-MSH as a Modulator of Ocular Immunobiology Exemplifies Mechanistic Differences between Melanocortins and Steroids. AB - Melanocortins are a highly conserved family of peptides and receptors that includes multiple proopiomelanocortin-derived peptides and five defined melanocortin receptors. The melanocortins have an important role in maintaining immune homeostasis and in suppressing inflammation. Within the healthy eye, the melanocortins have a central role in preventing inflammation and maintaining immune privilege. A central mediator of the anti-inflammatory activity is the non steroidogenic melanocortin peptide alpha-melanocyte stimulating hormone. In this review we summarize the major findings of melanocortin regulation of ocular immunobiology with particular interest in the ability of melanocortin to induce immune tolerance and cytoprotection. The melanocortins have therapeutic potential because their mechanisms of action in regulating immunity are distinctly different from the actions of steroids. PMID- 26807877 TI - Correction: A Novel Role for the TIR Domain in Association with Pathogen-Derived Elicitors. AB - [This corrects the article DOI: 10.1371/journal.pbio.0050068.]. PMID- 26807878 TI - Effect of Base-Pairing Partner on the Thermodynamic Stability of the Diastereomeric Spiroiminodihydantoin Lesion. AB - Oxidation of guanine by reactive oxygen species and high valent metals produces damaging DNA base lesions like 8-oxo-7,8-dihydroguanine (8-oxoG). 8-oxoG can be further oxidized to form the spiroiminodihydantoin (Sp) lesion, which is even more mutagenic. DNA polymerases preferentially incorporate purines opposite the Sp lesion, and DNA glycosylases excise the Sp lesion from the duplex, although the rate of repair is different for the two Sp diastereomers. To further understand the biological processing of the Sp lesion, differential scanning calorimetry studies were performed on a series of 15-mer DNA duplexes. The thermal and thermodynamic stabilities of each of the Sp diastereomers paired to the four standard DNA bases were investigated. It was found that, regardless of the base-pairing partner, the Sp lesion was always highly destabilizing in terms of DNA melting temperature, enthalpic stability, and overall duplex free energy. We found no significant differences between the two Sp diastereomers, but changing the base-pairing partner of the Sp lesion produced slight differences in stability. Specifically, duplexes with Sp:C pairings were always the most destabilized, whereas pairing the Sp lesion with a purine base modestly increased stability. Overall, these results suggest that, although the stability of the Sp diastereomers cannot explain the differences in the rates of repair by DNA glycosylases, the most stable base-pairing partners do correspond with the nucleotide preference of DNA polymerases. PMID- 26807879 TI - Photosensitizers binding to nucleic acids as anticancer agents. AB - Cationic porphyrins (Prs) and phthalocyanines (Pcs) are strong photosensitizers that have drawn much attention for their potential in photodynamic therapy. These compounds have the interesting property of binding to nucleic acids, in particular G-rich quadruplex-forming sequences in DNA and RNA. In this review, we highlight their potential as anticancer drugs. PMID- 26807880 TI - Investigation of a Suicide Ideation Risk Profile in People With Co-occurring Depression and Substance Use Disorder. AB - Disengagement from services is common before suicide, hence identifying factors at treatment presentation that predict future suicidality is important. This article explores risk profiles for suicidal ideation among treatment seekers with depression and substance misuse. Participants completed assessments at baseline and 6 months. Baseline demographics, psychiatric history, and current symptoms were entered into a decision tree to predict suicidal ideation at follow-up. Sixty-three percent of participants at baseline and 43.5% at follow-up reported suicidal ideation. Baseline ideation most salient when psychiatric illness began before adulthood, increasing the rate of follow-up ideation by 16%. Among those without baseline ideation, dysfunctional attitudes were the most important risk factor, increasing rates of suicidal ideation by 35%. These findings provide evidence of factors beyond initial diagnoses that increase the likelihood of suicidal ideation and are worthy of clinical attention. In particular, providing suicide prevention resources to those with high dysfunctional attitudes may be beneficial. PMID- 26807881 TI - The Association of Social Inhibition and Posttraumatic Stress Disorder: A Vicious Circle?: Results From the Population-Based KORA F4 Study With 1232 Participants With Trauma Exposure. AB - This cross-sectional analysis investigated the association between posttraumatic stress disorder (PTSD) and social inhibition (SI). A total of 1232 individuals aged 32-71 years with a history of traumatic experience were identified from the population-based Cooperative Health Research in the Region of Augsburg F4 study conducted in 2006-2008. PTSD was assessed by the Impact of Event Scale, Posttraumatic Diagnostic Scale, and interview data. SI was measured by the SI subscale of the German version of the Type-D scale and dichotomized in a high (score of >=10) and nonhigh group. Even in the fully adjusted multinomial logistic regression model (adjusted for age, sex, sociodemographic and metabolic risk factors, anxiety, depression), high levels of SI were significantly associated with PTSD (partial: odds ratio, 1.58; 95% confidence interval, 1.19 2.09; p = 0.002; full: odds ratio, 2.45; 95% confidence interval, 1.25-4.82; p = 0.009). Our findings suggest a dose-response relationship between PTSD and SI and should be integrated in individual therapy plans, especially of patients with interpersonal violence experience. PMID- 26807882 TI - The Influence of Urbanism and Information Consumption on Political Dimensions of Social Capital: Exploratory Study of the Localities Adjacent to the Core City from Brasov Metropolitan Area, Romania. AB - BACKGROUND: The last two decades have seen a growing trend towards the research of voting behavior in post-communist countries. Urban sociology theorists state that not only space structures influence political participation, but also space structures are changing under the influence of global, local, and individual factors. The growing role played by information in the globalised world has accelerated the paradigm shift in urban sociology: from central place model (based on urban-rural distinction and on monocentric metropolitan areas) to network society (based on space of flows and polycentric metropolitan areas). However, recent studies have mainly focused on countries with solid democracies, rather than on former communist countries. The present study aims to analyze the extent to which a new emerging spatial structure can be envisaged within a metropolitan area of Romania and its consequences for the political dimensions of social capital. METHODS: The Transilvania University Ethics Commission approved this study (S1 Aprouval). The research is based upon individual and aggregate empirical data, collected from the areas adjacent to the core city in Brasov metropolitan area. Individual data has been collected during October 2012, using the oral survey technique (S1 Survey), based on a standardized questionnaire (stratified simple random sample, N = 600). The National Institute of Statistics and the Electoral Register provided the aggregate data per locality. Unvaried and multivariate analyses (hierarchical regression method) were conducted based on these data. RESULTS: Some dimensions of urbanism, identified as predictors of the political dimensions of social capital, suggest that the area under analysis has a predominantly monocentric character, where the rural-urban distinction continues to remain relevant. There are also arguments favoring the dissolution of the rural-urban distinction and the emergence of polycentric spatial structures. The presence of some influences related to the information consumption on all six indicators of the political dimensions of social capital under analysis suggests the occurrence of emerging forms of a space of flows. The identified effects of social problems associated with transport infrastructure and of migration experience on the political dimensions of social capital, also support the emergence of space of flows. CONCLUSIONS: We recommend that, in the urban studies in former communist countries, conceptualization of urbanism as predictor of the political dimensions of social capital should consider both the material dimensions of space, as well as the dimensions of information consumption and migration experience. PMID- 26807883 TI - School bullying and susceptibility to smoking among never-tried cigarette smoking students. AB - INTRODUCTION: Bullying involvement has been linked with substance use; however, less is known about its relationship with pre-initiation stages of adolescent cigarette smoking behavior. This study examined the association between bullying involvement and smoking susceptibility among never tried or experimented with cigarette smoking students. Susceptibility to cigarette smoking in adolescence is a strong predictor of subsequent smoking initiation. METHODS: A cross-sectional data on Canadian adolescent and youth were drawn from the 2012/2013 Youth Smoking Survey (n=28,843). Logistic regression analysis was used to examine the association between bullying and smoking susceptibility among never-smoking students. RESULTS: About 21% self-reported involvement in bullying (as a bully, victim or both). Middle school students (grades 6-8) reported more involvement in bullying (24%) than those in grades 9-12 (16%). The multivariable analyses showed that the association between bullying and smoking susceptibility was significantly different by grade level. Middle school students involved in bullying had higher odds of smoking susceptibility compared to uninvolved students (bully, adjusted odds ratio [AOR]=2.54, 95% CI=1.73-3.74; victim, AOR=1.29, 95% CI=1.11-1.48; bully-victim, AOR=2.19, 95% CI=1.75-2.74). There were no significant associations between all subgroups of bullying and smoking susceptibility for grades 9-12 students. CONCLUSIONS: Students involved in bullying were more susceptible to smoking, although patterns of association varied by grade level. In particular, the findings highlight that non-smoking middle school students involved in bullying were susceptible to future smoking. PMID- 26807884 TI - Impacts of Groundwater Constraints on Saudi Arabia's Low-Carbon Electricity Supply Strategy. AB - Balancing groundwater depletion, socioeconomic development and food security in Saudi Arabia will require policy that promotes expansion of unconventional freshwater supply options, such as wastewater recycling and desalination. As these processes consume more electricity than conventional freshwater supply technologies, Saudi Arabia's electricity system is vulnerable to groundwater conservation policy. This paper examines strategies for adapting to long-term groundwater constraints in Saudi Arabia's freshwater and electricity supply sectors with an integrated modeling framework. The approach combines electricity and freshwater supply planning models across provinces to provide an improved representation of coupled infrastructure systems. The tool is applied to study the interaction between policy aimed at a complete phase-out of nonrenewable groundwater extraction and concurrent policy aimed at achieving deep reductions in electricity sector carbon emissions. We find that transitioning away from nonrenewable groundwater use by the year 2050 could increase electricity demand by more than 40% relative to 2010 conditions, and require investments similar to strategies aimed at transitioning away from fossil fuels in the electricity sector. Higher electricity demands under groundwater constraints reduce flexibility of supply side options in the electricity sector to limit carbon emissions, making it more expensive to fulfill climate sustainability objectives. The results of this analysis underscore the importance of integrated long-term planning approaches for Saudi Arabia's electricity and freshwater supply systems. PMID- 26807885 TI - Risk assessment of the cumulative acute exposure of Hungarian population to organophosphorus pesticide residues with regard to consumers of plant based foods. AB - Based on the Hungarian pesticide residues monitoring data of the last five years and the consumption data collected within a 3-day dietary record survey in 2009 (more than 2 million pesticide residue results and almost 5000, 0-101-year-old consumers 3 non-consecutive-day personal fruit and vegetable consumption data), the cumulative acute exposure of organophosphorus pesticide residues was evaluated. The relative potency factor approach was applied, with acephate chosen as index compound. According to our conservative calculation method, applying the measured residues only, the 99.95% of the 99th percentiles of calculated daily intakes was at or below 87 MUg/kgbwday, indicating that the cumulative acute exposure of the whole Hungarian population (including all age classes) to organophosphorus compounds was not a health concern. PMID- 26807886 TI - Estimated exposure to zearalenone, ochratoxin A and aflatoxin B1 through the consume of bakery products and pasta considering effects of food processing. AB - The objective of this research was to estimate the processing effect on mycotoxins levels and the exposure to zearalenone (ZEA), ochratoxin (OTA) and aflatoxin B1 (AFB1) through the consumption of pasta and bakery products. The higher reduction percentage of mycotoxins was observed in cake production (95, 90 and 70% for ZEA, OTA and AFB1, respectively). Bread and biscuit showed similar reduction in mycotoxins levels (89 and 90% for ZEA; 80 and 85% for OTA; 36 and 40% for AFB1, respectively). The lower reduction in the levels of mycotoxins has been observed for pasta (75, 65 and 10% for ZEA, OTA and AFB1, respectively). The consumption of these products could represent 12.6% of the maximum tolerable daily intake of ZEA and 30.5% of the tolerable weekly intake of OTA. The margin of exposure value related to the exposure to AFB1 was 24.6. The exposure to ZEA and OTA through the consumption of bakery products and pasta would not represent risk for consumer health, (although conjugated forms were not determined). However, the exposure to AFB1 represents a risk (even without considering the AFB1-conjugated forms). PMID- 26807888 TI - Modified Sublimis Tenodesis: Surgical Technique for Treating Chronic Traumatic Proximal Interphalangeal Joint Hyperextension Instability. AB - Many surgical techniques for treating chronic posttraumatic hyperextension instability of the proximal interphalangeal (PIP) joint involve exploration of the PIP joint, often leading to stiffness in an already traumatized joint. This article outlines the indications, contraindications, surgical technique, and postoperative management for a modified flexor digitorum sublimis tenodesis that utilizes 2 small incisions, a slip of flexor digitorum sublimis, a suture anchor, and temporary pinning of the PIP joint, while avoiding violation of the PIP capsule. PMID- 26807887 TI - Hydroquinone stimulates cell invasion through activator protein-1-dependent induction of MMP-9 in HepG2 human hepatoma cells. AB - Hydroquinone (HQ) is a well-known environmental carcinogen and exposure of humans to HQ can also occur through plant foods, cosmetics, and tobacco products. Although liver is a major organ metabolizing HQ and susceptible to its toxicity, role of HQ in metastatic progression of human hepatocellular carcinoma (HCC) remains unclear. In this study, we examined the effect of HQ on the invasion of HCC cells and its underlying molecular mechanisms. HQ strongly induced matrix metalloproteinase-9 (MMP-9) expression and secretion in HepG2 human hepatoma cells, which were well correlated with increased cell invasion. Mechanistic studies further demonstrated that HQ induced transcriptional activity of MMP-9 gene by activating activator protein-1 (AP-1), the well-known key element mediating MMP-9 gene expression, via MAP kinase (MAPK) signaling pathways. These results suggest that HQ may promote metastatic progression of HCC, although data on in vivo hydroquinone exposure and risk for HCC are contradictory. PMID- 26807889 TI - Assessing the Relative Contributions of Active Ankle and Knee Assistance to the Walking Mechanics of Transfemoral Amputees Using a Powered Prosthesis. AB - Powered knee-ankle prostheses are capable of providing net-positive mechanical energy to amputees. Yet, there are limitless ways to deliver this energy throughout the gait cycle. It remains largely unknown how different combinations of active knee and ankle assistance affect the walking mechanics of transfemoral amputees. This study assessed the relative contributions of stance phase knee swing initiation, increasing ankle stiffness and powered plantarflexion as three unilateral transfemoral amputees walked overground at their self-selected walking speed. Five combinations of knee and ankle conditions were evaluated regarding the kinematics and kinetics of the amputated and intact legs using repeated measures analyses of variance. We found eliminating active knee swing initiation or powered plantarflexion was linked to increased compensations of the ipsilateral hip joint during the subsequent swing phase. The elimination of knee swing initiation or powered plantarflexion also led to reduced braking ground reaction forces of the amputated and intact legs, and influenced both sagittal and frontal plane loading of the intact knee joint. Gradually increasing prosthetic ankle stiffness influenced the shape of the prosthetic ankle plantarflexion moment, more closely mirroring the intact ankle moment. Increasing ankle stiffness also corresponded to increased prosthetic ankle power generation (despite a similar maximum stiffness value across conditions) and increased braking ground reaction forces of the amputated leg. These findings further our understanding of how to deliver assistance with powered knee-ankle prostheses and the compensations that occur when specific aspects of assistance are added/removed. PMID- 26807890 TI - Temporal Doppler Effect and Future Orientation: Adaptive Function and Moderating Conditions. AB - The objectives of this study were to examine whether the temporal Doppler effect exists in different time intervals and whether certain individual and environmental factors act as moderators of the effect. Using hierarchical linear modeling, we examined the existence of the temporal Doppler effect and the moderating effect of future orientation among 139 university students (Study 1), and then the moderating conditions of the temporal Doppler effect using two independent samples of 143 and 147 university students (Studies 2 and 3). Results indicated that the temporal Doppler effect existed in all of our studies, and that future orientation moderated the temporal Doppler effect. Further, time interval perception mediated the relationship between future orientation and the motivation to cope at long time intervals. Finally, positive affect was found to enhance the temporal Doppler effect, whereas control deprivation did not influence the effect. The temporal Doppler effect is moderated by the personality trait of future orientation and by the situational variable of experimentally manipulated positive affect. We have identified personality and environmental processes that could enhance the temporal Doppler effect, which could be valuable in cases where attention to a future task is necessary. PMID- 26807891 TI - Are there too many "times-to-pregnancy"? AB - The time between marriage and the birth of the first child has been used by demographers as a measure of fecundity, but such a measure only works if cohabitation and wanting to have a child are closely linked to marriage. In a world where pregnancies can be planned for those who have access to safe contraception methods, couples may know their "time-to-pregnancy" (TTP) as the waiting time from when they stopped using contraceptive methods until becoming pregnant or being classified as infertile (a period of >= 12 months). This TTP measure was first used in 1981 (1) as a measure of couple fecundity and it has been applied widely with success and failure in many areas of research including work-related fecundity problems (2, 3, 4). In this letter, some less well-known limitations of the TTP measure are discussed. PMID- 26807892 TI - US Findings in Patients at Risk for Pancreas Transplant Failure. AB - Purpose To determine if ultrasonographic (US) findings, including Doppler US findings, are associated with subsequent pancreas transplant failure. Materials and Methods A cohort of adult patients who underwent pancreas transplantation at a tertiary institution over the course of 10 years (from 2003 to 2012) was retrospectively evaluated for failure, which was defined as return to insulin therapy or surgical graft removal. The institutional review board provided a waiver of informed consent. All US images obtained within the 1st postoperative year were reviewed for three findings: arterial flow (presence or absence of intraparenchymal forward diastole flow), splenic vein thrombus, and edema. These findings were correlated with pancreas graft failure within 1-year after surgery by using Cox proportional hazards models and hazard ratios. Results A total of 228 transplants were included (mean patient age, 41.6 years; range, 19-57 years; 122 men, 106 women). Absent or reversed arterial diastolic flow was identified in nine of 20 failed transplants (sensitivity, 45%; 95% confidence interval [CI]: 23, 68) and in 15 of 208 transplants that survived (specificity, 93% [193 of 208]; 95% CI: 89, 96). The Cox proportional hazard ratio was 6.2 (95% CI: 3.1, 12.4). Splenic vein thrombus was identified in 10 of 20 failed transplants (sensitivity, 50%; 95% CI: 27, 73) and in 25 of 208 transplants that survived (specificity, 88% [183 of 208]; 95% CI: 83, 92). The Cox proportional hazard ratio was 4.2 (95% CI: 2.4, 7.4). Edema had the lowest specificity (Cox proportional hazard ratio, 2.0; 95% CI: 1.3, 2.9). In the multivariate analysis, only absent or reversed arterial diastolic flow remained significantly associated with transplant failure (adjusted hazard ratio, 3.6; 95% CI: 1.0, 12.8; P = .045). Conclusion Absent or reversed diastolic arterial Doppler flow has a stronger association with transplant failure than does splenic vein thrombus or edema. ((c)) RSNA, 2016. PMID- 26807893 TI - Accuracy of Unenhanced MR Imaging in the Detection of Acute Appendicitis: Single Institution Clinical Performance Review. AB - PURPOSE: To determine the accuracy of unenhanced magnetic resonance (MR) imaging in the detection of acute appendicitis in patients younger than 50 years who present to the emergency department with right lower quadrant (RLQ) pain. MATERIALS AND METHODS: The institutional review board approved this retrospective study of 403 patients from August 1, 2012, to July 30, 2014, and waived the informed consent requirement. A cross-department strategy was instituted to use MR imaging as the primary diagnostic modality in patients aged 3-49 years who presented to the emergency department with RLQ pain. All MR examinations were performed with a 1.5- or 3.0-T system. Images were acquired without breath holding by using multiplanar half-Fourier single-shot T2-weighted imaging without and with spectral adiabatic inversion recovery fat suppression without oral or intravenous contrast material. MR imaging room time was measured for each patient. Prospective image interpretations from clinical records were reviewed to document acute appendicitis or other causes of abdominal pain. Final clinical outcomes were determined by using (a) surgical results (n = 77), (b) telephone follow-up combined with review of the patient's medical records (n = 291), or (c) consensus expert panel assessment if no follow-up data were available (n = 35). Logistic regression analysis was performed to evaluate the sensitivity and specificity of MR imaging in the detection of acute appendicitis, and corresponding 95% confidence intervals were determined. RESULTS: Of the 403 patients, 67 had MR imaging findings that were positive for acute appendicitis, and 336 had negative findings. MR imaging had a sensitivity of 97.0% (65 of 67) and a specificity of 99.4% (334 of 336). The mean total room time was 14 minutes (range, 8-62 minutes). An alternate diagnosis was offered in 173 (51.5%) of 336 patients. CONCLUSION: MR imaging is a highly sensitive and specific test in the evaluation of patients younger than 50 years with acute RLQ pain that uses a rapid imaging protocol performed without intravenous or oral contrast material. PMID- 26807894 TI - Volume of Bone Metastasis Assessed with Whole-Body Diffusion-weighted Imaging Is Associated with Overall Survival in Metastatic Castration-resistant Prostate Cancer. AB - Purpose To determine the correlation between the volume of bone metastasis as assessed with diffusion-weighted (DW) imaging and established prognostic factors in metastatic castration-resistant prostate cancer (mCRPC) and the association with overall survival (OS). Materials and Methods This retrospective study was approved by the institutional review board; informed consent was obtained from all patients. The authors analyzed whole-body DW images obtained between June 2010 and February 2013 in 53 patients with mCRPC at the time of starting a new line of anticancer therapy. Bone metastases were identified and delineated on whole-body DW images in 43 eligible patients. Total tumor diffusion volume (tDV) was correlated with the bone scan index (BSI) and other prognostic factors by using the Pearson correlation coefficient (r). Survival analysis was performed with Kaplan-Meier analysis and Cox regression. Results The median tDV was 503.1 mL (range, 5.6-2242 mL), and the median OS was 12.9 months (95% confidence interval [CI]: 8.7, 16.1 months). There was a significant correlation between tDV and established prognostic factors, including hemoglobin level (r = -0.521, P < .001), prostate-specific antigen level (r = 0.556, P < .001), lactate dehydrogenase level (r = 0.534, P < .001), alkaline phosphatase level (r = 0.572, P < .001), circulating tumor cell count (r = 0.613, P = .004), and BSI (r = 0.565, P = .001). A higher tDV also showed a significant association with poorer OS (hazard ratio, 1.74; 95% CI: 1.02, 2.96; P = .035). Conclusion Metastatic bone disease from mCRPC can be evaluated and quantified with whole-body DW imaging. Whole-body DW imaging-generated tDV showed correlation with established prognostic biomarkers and is associated with OS in mCRPC. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 26807895 TI - Comparison of Diffusion-Weighted Imaging in the Human Brain Using Readout Segmented EPI and PROPELLER Turbo Spin Echo With Single-Shot EPI at 7 T MRI. AB - OBJECTIVES: The purpose of the present study was to compare periodically rotated overlapping parallel lines with enhanced reconstruction-type turbo spin echo diffusion-weighted imaging (pTSE-DWI) and readout-segmented echo planar imaging (rsEPI-DWI) with single-shot echo planar imaging (ssEPI-DWI) in a 7 T human MR system. We evaluated the signal-to-noise ratio (SNR), image distortion, and apparent diffusion coefficient values in the human brain. MATERIALS AND METHODS: Six healthy volunteers were included in this study. The study protocol was approved by our institutional review board. All measurements were performed at 7 T using pTSE-DWI, rsEPI-DWI, and ssEPI-DWI sequences. The spatial resolution was 1.2 * 1.2 mm in-plane with a 3-mm slice thickness. Signal-to-noise ratio was measured using 2 scans. RESULTS: The ssEPI-DWI sequence showed significant image blurring, whereas pTSE-DWI and rsEPI-DWI sequences demonstrated high image quality with low geometrical distortion compared with reference T2-weighted, turbo spin echo images. Signal loss in ventral regions near the air-filled paranasal sinus/nasal cavity was found in ssEPI-DWI and rsEPI-DWI but not pTSE DWI. The apparent diffusion coefficient values for ssEPI-DWI were 824 +/- 17 * 10 and 749 +/- 25 * 10 mm/s in the gray matter and white matter, respectively; the values obtained for pTSE-DWI were 798 +/- 21 * 10 and 865 +/- 40 * 10 mm/s; and the values obtained for rsEPI-DWI were 730 +/- 12 * 10 and 722 +/- 25 * 10 mm/s. The pTSE-DWI images showed no additional distortion comparison to the T2-weighted images, but had a lower SNR than ssEPI-DWI and rsEPI-DWI. The rsEPI-DWI sequence provided high-quality images with minor distortion and a similar SNR to ssEPI DWI. CONCLUSIONS: Our results suggest that the benefits of the rsEPI-DWI and pTSE DWI sequences, in terms of SNR, image quality, and image distortion, appear to outweigh those of ssEPI-DWI. Thus, pTSE-DWI and rsEPI-DWI at 7 T have great potential use for clinical diagnoses. However, it is noteworthy that both sequences are limited by the scan time required. In addition, pTSE-DWI has limitations on the number of slices due to specific absorption rate. Overall, rsEPI-DWI is a favorable imaging sequence, taking into account the SNR and image quality at 7 T. PMID- 26807896 TI - The Short Breath-Hold Technique, Controlled Aliasing in Parallel Imaging Results in Higher Acceleration, Can Be the First Step to Overcoming a Degraded Hepatic Arterial Phase in Liver Magnetic Resonance Imaging: A Prospective Randomized Control Study. AB - OBJECTIVE: The aim of this study was to assess whether a short breath-hold technique can improve hepatic arterial phase (HAP) image quality in gadoxetic acid-enhanced magnetic resonance (MR) imaging compared with a conventional long breath-hold technique. MATERIALS AND METHODS: Institutional review board approval and patient consent were obtained for this prospective randomized control study. One hundred nineteen patients undergoing gadoxetic acid-enhanced MR imaging were randomly assigned to groups A or B. Group A patients underwent an 18-second long breath-hold MR technique (conventional VIBE [volumetric interpolated breath-hold examination] technique with GRAPPA [generalized autocalibrating partially parallel acquisition]), and group B patients underwent a 13-second short breath hold MR technique (VIBE technique with CAIPIRINHA [controlled aliasing in parallel imaging results in higher acceleration]). Respiratory-related graphs of the precontrast and HAP were acquired. The breath-hold degree was graded based on the standard deviation (SD) value of respiratory waveforms. Gadoxetic acid related dyspnea was defined as when the SD value of the HAP was 200 greater than that of the precontrast phase without degraded image quality in the portal and transitional phases (SD value of the HAP - SD value of the precontrast phase). The overall image quality and motion artifacts of the precontrast and HAP images were evaluated. The groups were compared using the Student t or Fisher exact test, as appropriate. RESULTS: The incidence of breath-holding difficulty (breath hold grades 3 and 4) during the HAP was 43.6% (27/62) and 36.8% (21/57) for group A and B, respectively. The SD value during the precontrast phase and the SD value difference between the precontrast and HAP were both significantly higher in group A than in group B (P = 0.047 and P = 0.023, respectively). Gadoxetic acid related dyspnea was seen in 19.4% (12/62) of group A and 7.0% (4/57) of group B. Group B showed better precontrast and HAP image quality than group A (P < 0.001). Degraded HAP (overall image quality >=4) was observed in 9.7% (6/62) and 3.5% (2/57) of group A and B, respectively. CONCLUSIONS: The short breath-hold MR technique, CAIPIRINHA, showed better HAP image quality with less degraded HAP and a lower incidence of breath-hold difficulty and gadoxetic acid-related dyspnea than the conventional long breath-hold technique. PMID- 26807897 TI - Cryopreserved Ultra-Thick Human Amniotic Membrane for Conjunctival Surface Reconstruction After Excision of Conjunctival Tumors. AB - PURPOSE: Cryopreserved ultra-thick human amniotic membrane (AM) is used for glaucoma surgery. We evaluated the use of cryopreserved ultra-thick human AM for conjunctival surface reconstruction after excision of a conjunctival tumor. METHODS: We retrospectively reviewed the medical records of 28 patients who underwent conjunctival surface reconstruction with cryopreserved ultra-thick human AM after excision of the tumor. The AM was secured to the surrounding conjunctiva and underlying sclera with interrupted 8-0 Vicryl sutures. Clinical data regarding demographics, diagnosis, size and location of conjunctival tumors, patient outcome, and complications were gathered. RESULTS: Of 28 patients, 6 (21.4%) had malignant melanoma, 4 (14.3%) had squamous cell carcinoma, 6 (21.4%) had conjunctival intraepithelial neoplasia, 1 (3.6%) had sebaceous carcinoma, 1 (3.6%) had mucoepidermoid carcinoma, 1 (3.6%) had conjunctival intraepithelial dysplasia, 5 (17.9%) had pterygium, 2 (7.1%) had compound nevus, 1 (3.6%) had a large epithelial inclusion cyst, and 1 (3.6%) patient had a granuloma. The mean area of graft size was 156 +/- 120 mm2. Postoperatively, the graft was well tolerated with no failure, discomfort, or dehiscence. During the 17-month mean follow-up, symblepharon, which was clinically nonsignificant, developed in 3 (11%) patients and partial stem cell deficiency was noted in 5 (18%) patients. CONCLUSIONS: Cryopreserved ultra-thick human AM is a well-tolerated, effective graft material that is easy to handle. It is a viable alternative for conjunctival surface reconstruction after excision of a conjunctival tumor. PMID- 26807898 TI - Randomized Trial Comparing Amniotic Membrane Transplantation with Lamellar Corneal Graft for the Treatment of Corneal Thinning. AB - PURPOSE: There are few studies comparing different surgical procedures for the treatment of corneal thinning. Lamellar corneal transplantation (LCT) has been reported to be efficient, but its results can be jeopardized by allograft rejection, opacification, or high astigmatism. Amniotic membrane transplantation (AMT) has been considered a good alternative, but it is not as resistant as LCT and the tissue can be reabsorbed after surgery. METHODS: A prospective, randomized, interventional, and comparative study of consecutive patients with corneal thinning over 6 months was performed. Ophthalmological examination was performed before transplant surgery and then repeated 1, 7, 15, 30, 90, and 180 days after surgery and ultrasound biomicroscopy was performed before and then 30, 90, and 180 days after surgery to assess corneal thinning. RESULTS: Herpes simplex infection was the main cause of corneal thinning (9 eyes), followed by surgery (cataract, glaucoma, 5 cases), rheumatoid arthritis (1), chemical burn (1), perforating trauma (1), previous band keratopathy treatment (1), and Stevens Johnson syndrome (1). Although all patients showed significant increase in final thickness in the area of thinning, it was higher in those submitted to LCT at 180 days postoperatively. Regardless of the surgical technique, all patients showed epithelialization. Patients undergoing AMT showed an 89% decrease in neovascularization. Final corrected distance visual acuity was better in patients submitted to AMT. CONCLUSIONS: LCT proved to be the best option for treating corneal thinning. AMT represents an alternative that allows good visual recovery but does not restore corneal thickness as efficiently as LCT. PMID- 26807899 TI - Effects of Capsaicin and Carbachol on Secretion From Transplanted Submandibular Glands and Prevention of Duct Obstruction. AB - PURPOSE: To investigate whether capsaicin and carbachol promote secretion from and prevent duct obstruction in transplanted submandibular glands (SMGs). METHODS: This retrospective cohort study included consecutive patients with severe keratoconjunctivitis sicca and successful SMG transplantation. Patients were divided into 2 groups: an exposed group receiving both capsaicin and carbachol after surgery and an unexposed group receiving neither. Secretion changes in response to capsaicin and carbachol administration were recorded in the exposed group. The main outcome measures were the secretory flow rate and duct obstruction rate in the transplanted SMGs. RESULTS: Forty-four patients (44 eyes) in the unexposed group and 115 patients (128 eyes) in the exposed group were followed up for more than 3 months postoperatively. The baseline characteristics were similar between the groups. The secretory flow rate before and 5, 25, 55 minutes after administration was 1 mm (0-2 mm) (median with interquartile range), 3 mm (1-5 mm), 4 mm (2-5 mm), 1 mm (0-2.5 mm), respectively, for capsaicin and 1 mm (0-3 mm), 1050 mm (450-1500 mm), 375 mm (150 600 mm), 0 mm (0-150 mm), respectively, for carbachol (P < 0.001 for both). In the exposed group, 6.2% of eyes had duct obstruction, whereas 18.2% of eyes in the unexposed group had duct obstruction (P = 0.031) (odds ratio = 0.3, 95% confidence interval, 0.105-0.856). CONCLUSIONS: This study provides evidence that capsaicin and carbachol effectively promote secretion from and prevent duct obstruction in transplanted SMGs during at least 3 months after transplantation. PMID- 26807900 TI - Comparison of Topical Application of TSG-6, Cyclosporine, and Prednisolone for Treating Dry Eye. AB - PURPOSE: To compare the therapeutic effects of topical tumor necrosis factor (TNF)-alpha-stimulated gene/protein-6 (TSG-6) with those of cyclosporine and prednisolone eye drops in NOD.B10.H2 mice, a model for inflammation-mediated dry eye. METHODS: The 12-week-old NOD.B10.H2 mice were topically administered recombinant TSG-6 (0.1%) 4 times a day, 0.05% cyclosporine (Restasis) twice a day, or 1% prednisolone (Pred Forte) 4 times a day for 1 week. Aqueous tear production was measured by phenol red thread test, and corneal epithelial damage was observed with lissamine green and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Conjunctival goblet cell number was evaluated with periodic acid-Schiff staining. The levels of inflammatory cytokines were analyzed in the ocular surface (cornea and conjunctiva) and intraorbital gland. The dose dependent effects of topical TSG-6 (0.001, 0.01, and 0.1%) were tested. RESULTS: Tear production and goblet cell density were significantly increased in all groups receiving TSG-6, cyclosporine, and prednisolone. Corneal epithelial staining was markedly reduced by TSG-6 and cyclosporine but not by prednisolone. In prednisolone-treated eyes, corneal epithelial thickness was decreased, and apoptosis of corneal epithelial cells was increased. The levels of interferon gamma and TNF-alpha in the ocular surface and intraorbital gland were significantly repressed by TSG-6 and cyclosporine, and prednisolone treatment significantly reduced the level of interferon gamma. The effects of TSG-6 on the ocular surface and tear production were dose dependent. CONCLUSIONS: Topical TSG 6 was as effective in inflammation-mediated dry eye as cyclosporine eye drops. Topical prednisolone suppressed inflammation but induced apoptosis in the corneal epithelium. PMID- 26807901 TI - Anterior Chamber Air Bubble to Achieve Graft Attachment After DMEK: Is Bigger Always Better? AB - PURPOSE: To analyze the influence of the size of the air bubble subsequent to Descemet membrane endothelial keratoplasty (DMEK) surgery on the rate of graft detachment and need for rebubbling, the incidence of pupillary block, and the observed endothelial cell loss. METHODS: This is a single-center, retrospective, consecutive case series of 74 cases undergoing DMEK and fulfilling the inclusion criteria concerning the size of the air bubble at the end of surgery. Based on the medical records, patients were divided into 2 groups (n = 37, respectively). The first group had an air bubble with a volume of approximately 50% and the second group of approximately 80% of the anterior chamber (AC) volume, respectively. Patients who did not comply with instructions to remain in the supine position until complete resorption of AC air or cases in which difficulties in graft preparation (eg, radial breaks) occurred were excluded from data analysis. The central corneal thickness and endothelial cell density were measured 6 months after surgery. RESULTS: Ten of 37 patients (27.0%) in the 50% air bubble group and 3 of 37 patients (8.1%) in the 80% air bubble group needed 1 rebubbling procedure (P = 0.032). There was no difference between the groups after 6 months regarding endothelial cell density and central corneal thickness. No pupillary block was observed. CONCLUSIONS: Larger air bubbles of 80% anterior chamber volume decrease the risk of graft detachment after DMEK with no detrimental effect on the outcome and risk for pupillary block. PMID- 26807902 TI - Novel Technique for Rebubbling DMEK Grafts at the Slit Lamp Using Intravenous Extension Tubing. AB - PURPOSE: To describe a novel technique for rebubbling DMEK grafts at the slit lamp using a cannula coupled to a syringe with intravenous (IV) extension tubing. METHODS: We present a retrospective case series of eyes that underwent rebubbling using a novel technique at the slit lamp. The rebubbling apparatus is assembled using a standard 43-inch IV extension tube, a 5-cc luer lock syringe, and a 27 gauge cannula. The cannula is screwed onto one end of the extension tubing, and a 5-cc syringe that has been filled with air is screwed onto the opposite end. With the patient seated at the slit lamp, the cannula is positioned in the anterior chamber by the surgeon with one hand while the other hand operates the syringe and the joystick. RESULTS: We performed 5 rebubbling procedures at the slit lamp using a standard syringe and cannula. Despite suboptimal ergonomics with this approach, all of these cases achieved sufficient air fills without any complications. Four rebubbling procedures were subsequently performed at the slit lamp using our novel rebubbling technique. All of these cases also attained sufficient air fills without complications, but they were noted to be much easier to perform by the surgeon. CONCLUSIONS: Using IV extension tubing to couple a syringe to a cannula for rebubbling DMEK grafts at the slit lamp is ergonomically superior to the conventional alternative of using a standard cannula on a syringe. The technique is also simple and inexpensive to adopt. PMID- 26807903 TI - Electrical Stimulation of the Trigeminal Ganglion and Intrathecal Drug Delivery Systems for the Management of Corneal Neuropathic Pain. AB - PURPOSE: This case study reports on 2 novel neuromodulatory approaches in the management of a particularly recalcitrant case of corneal neuropathic pain. METHODS: Report of a case RESULTS: : A 32-year-old woman presented with intractable bilateral dry eye-like symptoms and corneal neuropathic pain after undergoing laser in situ keratomileusis surgery. Extensive ocular and systemic therapies were unsuccessful. Implantation of an electrode for the electrical stimulation of the trigeminal ganglion resulted in complete resolution of symptoms, but pain recurred after lead migration. Implantation of an intrathecal infusion system for fentanyl and bupivacaine delivery at the C1-C2 level resulted in control of her symptoms with excellent pain relief for more than 1 year. CONCLUSIONS: Electrical stimulation of the trigeminal ganglion and a high cervical intrathecal pain pump can be used in the management of corneal neuropathic pain unresponsive to ocular and systemic approaches. PMID- 26807904 TI - Evaluation of Time to Donor Lenticule Apposition Using Intraoperative Optical Coherence Tomography in Descemet Stripping Automated Endothelial Keratoplasty. AB - PURPOSE: To evaluate the time to donor lenticule apposition in cases of Descemet stripping automated endothelial keratoplasty (DSAEK) using microscope-integrated intraoperative optical coherence tomography (iOCT). METHODS: Thirty eyes of 27 patients planned to undergo Descemet stripping automated endothelial keratoplasty were enrolled in this prospective study. In group I (n = 10), continuous intracameral positive pressure was maintained for 8 minutes. In group II (n = 10) and group III (n = 10), external corneal massage was initiated simultaneously with positive intracameral air pressure. The external corneal massage was continued till complete resolution of interface fluid; the positive intracameral pressure was maintained for 8 minutes in group II and for 5 minutes in group III. The host-donor relationship was continuously monitored with the iOCT. The main outcome measure was time to complete donor lenticule apposition. RESULTS: In group I, the interface fluid persisted after 8 minutes of positive intracameral pressure in all eyes (10/10); hence an external corneal massage was required to achieve optimal donor adherence. In groups II and III, all eyes (20/20) had complete resolution of the interface fluid at the end of 3 minutes. In 100% of the eyes (30/30), the grafts were attached after anterior chamber decompression as seen on the iOCT. In all cases, the donor lenticules were adhered in the postoperative period. CONCLUSIONS: iOCT helps in understanding that the donor lenticule is well apposed within 1 to 3 minutes with the technique of simultaneous positive intracameral pressure and external corneal massage. This knowledge minimizes the waiting time for graft apposition and prevents prolonged intraocular pressure elevation. PMID- 26807905 TI - Evaluating the Toxicity/Fixation Balance for Corneal Cross-Linking With Sodium Hydroxymethylglycinate (SMG) and Riboflavin-UVA (CXL) in an Ex Vivo Rabbit Model Using Confocal Laser Scanning Fluorescence Microscopy. AB - PURPOSE: To develop methods to delineate the relationship between endothelial cell toxicity and tissue fixation (toxicity/fixation) using sodium hydroxymethylglycinate (SMG), a formaldehyde releaser, and riboflavin-UVA photochemical corneal cross-linking (CXL) for therapeutic tissue cross-linking of the cornea. METHODS: Eleven fresh cadaveric rabbit heads were used for ex vivo corneal cross-linking simulation. After epithelial debridement, the tissue was exposed to 1/4 max (9.8 mM) or 1/3 max (13 mM) SMG at pH 8.5 for 30 minutes or riboflavin-UVA (CXL). The contralateral cornea served as a paired control. Postexposure, cross-linking efficacy was determined by thermal denaturation temperature (Tm) and endothelial damage was assessed using calcein AM and ethidium homodimer staining (The Live/Dead Kit). Confocal laser scanning fluorescence microscopy was used to generate live/dead cell counts using a standardized algorithm. RESULTS: The DeltaTm after CXL, 1/3 SMG, and 1/4 SMG was 2.2 +/- 0.9 degrees C, 1.3 +/- 0.5 degrees C, and 1.1 +/- 0.5 degrees C, respectively. Endothelial cell damage was expressed as the percent of dead cells/live + dead cells counted per high-power field. The values were 3 +/- 1.7% (control) and 8.9 +/- 11.1% (CXL) (P = 0.390); 1 +/- 0.2% (control) and 19.5 +/- 32.2% (1/3 max SMG) (P = 0.426); and 2.7 +/- 2.4% (control) and 2.8 +/- 2.2% (1/4 max SMG) (P = 0.938). The values for endothelial toxicity were then indexed over the shift in Tm to yield a toxicity/fixation index. The values were as follows: 2.7 for CXL, 14 for 1/3 max, and 0.1 for 1/4 max. CONCLUSIONS: Quarter max (1/4 max = 9.8 mM) SMG effectively cross-linked tissue and was nontoxic to endothelial cells. Thus, SMG is potentially a compound that could achieve both desired effects. PMID- 26807906 TI - Dry Eye Disease Is Already Present in Hematological Patients Before Hematopoietic Stem Cell Transplantation. AB - PURPOSE: To analyze ocular surface parameters in patients before hematopoietic stem cell transplantation (HSCT) and to correlate them with hematological characteristics. METHODS: This is a retrospective analysis of prospectively collected data from 203 patients undergoing HSCT. Demographic data and hematological parameters (disorder type and stage) were collected from clinical charts. Ocular surface parameters (ocular surface disease index; Schirmer test I; tear film break-up time; corneal esthesiometry; and corneal and conjunctival staining) were analyzed the day before beginning the conditioning treatment for HSCT preparation. RESULTS: A high prevalence of dry eye (DE) was found: 116 patients (57.2%) were diagnosed as not suffering from DE, whereas 87 patients (42.8%) were diagnosed as having DE. Of these, 26 were classified as dry eye workshot (DEWS) severity score 1, 46 as DEWS score 2, and 15 as DEWS score 3. Tear film break-up time was found to be the only parameter statistically worse in the chronic lymphoproliferative disorder group compared with the stem cell malignancy group. Older age [odds ratio (OR) 1.03], female sex (OR 2.03), advanced stage of hematological disease (OR 1.4), and previous auto- or allo-HSCT (OR 1.9) showed a significant positive association in predicting DE onset before transplantation. CONCLUSIONS: DE was already present in a significant number of patients suffering from hematological disease before HSCT. Some hematological parameters seemed to influence this percentage. These results highlight the role of ocular surface examination by an ophthalmologist in hematological patients before HSCT, with the aim of diagnosing and, if necessary, treating DE patients early. PMID- 26807907 TI - Reply. PMID- 26807909 TI - Tuning the Electronic Coupling and Electron Transfer in Mo2 Donor-Acceptor Systems by Variation of the Bridge Conformation. AB - Assembling two quadruply bonded dimolybdenum units [Mo2 (DAniF)3 ](+) (DAniF=N,N' di(p-anisyl)formamidinate) with 1,4-naphthalenedicarboxylate and its thiolated derivatives produced three complexes [{Mo2 (DAniF)3 }2 (MU-1,4-O2 CC10 H6 CO2 )], [{Mo2 (DAniF)3 }2 (MU-1,4-OSCC10 H6 COS)], and [{Mo2 (DAniF)3 }2 (MU-1,4-S2 CC10 H6 CS2 )]. In the X-ray structures, the naphthalene bridge deviates from the plane defined by the two Mo-Mo bond vectors with the torsion angle increasing as the chelating atoms of the bridging ligand vary from O to S. The mixed-valent species exhibit intervalence transition absorption bands with high energy and very low intensity. In comparison with the data for the phenylene analogues, the optically determined electronic coupling matrix elements (Hab =258-345 cm(-1) ) are lowered by a factor of two or more, and the electron-transfer rate constants (ket ~10(11) s(-1) ) are reduced by about one order of magnitude. These results show that, when the electron-transporting ability of the bridge and electron donating (electron-accepting) ability of the donor (acceptor) are both variable, the former plays a dominant role in controlling the intramolecular electron transfer. DFT calculations revealed that increasing the torsion angle enlarges the HOMO-LUMO energy gap by elevating the (bridging) ligand-based LUMO energy. Therefore, our experimental results and theoretical analyses verify the superexchange mechanism for electronic coupling and electron transfer. PMID- 26807908 TI - Low Serum 25-Hydroxyvitamin D Levels Are Associated with Dry Eye Syndrome. AB - BACKGROUND: Dry eye syndrome (DES) is a common tear film and ocular surface disease that results in discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. Systemic diseases associated with DES include diabetes mellitus, rheumatoid arthritis, depression, anxiety, thyroid disease, allergic diseases, irritable bowel syndrome, chronic pain syndrome, and hyperlipidemia. Interestingly, it has been found that most of these are associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) or inadequate sunlight exposure. METHODS: In this cross-sectional data analysis, noninstitutionalized adults aged >=19 years (N = 17,542) who participated in Korean National Health and Nutrition Examination Survey 2010-2012 were included. Information regarding duration of sunlight exposure was collected from the survey participants. Serum 25(OH)D and zinc levels were measured. The confounding variables were age, gender, sunlight exposure time, region of residence, obesity, serum 25(OH)D level, diabetes mellitus, rheumatoid arthritis, depression, thyroid disorder, atopic dermatitis, history of ocular surgery, regular exercise, and walking exercise. RESULTS: Mean serum 25(OH)D levels of subjects with and without DES were 16.90 +/- 6.0 and 17.52 +/- 6.07 (p<0.001). Inadequate sunlight exposure time (odds ratio [OR], 1.554; 95% confidence interval [CI], 1.307-1.848), urban residence (OR, 1.669; 95% CI, 1.456-1.913), indoor occupation (OR, 1.578; 95% CI, 1.389-1.814), and low serum 25(OH)D level (OR, 1.158; 95% CI, 1.026-1.308) were the risk factors for DES. After adjusting for age, sex, obesity, diabetes mellitus, rheumatoid arthritis, depression, thyroid disorder, atopic dermatitis, history of ocular surgery, regular exercise, and occupation, low serum 25(OH)D level (OR, 1.178; 95% CI, 1.010-1.372) and deficient sunlight exposure time (OR, 1.383; 95% CI, 1.094-1.749) were the risk factors for diagnosed DES. CONCLUSION: Low serum 25(OH)D levels and inadequate sunlight exposure are associated with DES in Korean adults. These results suggest that sufficient sunlight exposure or vitamin D supplementation may be useful in DES treatment. PMID- 26807910 TI - Development of a Genomic Resource and Quantitative Trait Loci Mapping of Male Calling Traits in the Lesser Wax Moth, Achroia grisella. AB - In the study of sexual selection among insects, the Lesser Waxmoth, Achroia grisella (Lepidoptera: Pyralidae), has been one of the more intensively studied species over the past 20 years. Studies have focused on how the male calling song functions in pair formation and on the quantitative genetics of male song characters and female preference for the song. Recent QTL studies have attempted to elucidate the genetic architecture of male song and female preference traits using AFLP markers. We continued these QTL studies using SNP markers derived from an EST library that allowed us to measure both DNA sequence variation and map loci with respect to the lepidopteran genome. We report that the level of sequence variation within A. grisella is typical among other Lepidoptera that have been examined, and that comparison with the Bombyx mori genome shows that macrosynteny is conserved. Our QTL map shows that a QTL for a male song trait, pulse-pair rate, is situated on the Z chromosome, a prediction for sexually selected traits in Lepidoptera. Our findings will be useful for future studies of genetic architecture of this model species and may help identify the genetics associated with the evolution of its novel acoustic communication. PMID- 26807911 TI - CERENA: ChEmical REaction Network Analyzer--A Toolbox for the Simulation and Analysis of Stochastic Chemical Kinetics. AB - Gene expression, signal transduction and many other cellular processes are subject to stochastic fluctuations. The analysis of these stochastic chemical kinetics is important for understanding cell-to-cell variability and its functional implications, but it is also challenging. A multitude of exact and approximate descriptions of stochastic chemical kinetics have been developed, however, tools to automatically generate the descriptions and compare their accuracy and computational efficiency are missing. In this manuscript we introduced CERENA, a toolbox for the analysis of stochastic chemical kinetics using Approximations of the Chemical Master Equation solution statistics. CERENA implements stochastic simulation algorithms and the finite state projection for microscopic descriptions of processes, the system size expansion and moment equations for meso- and macroscopic descriptions, as well as the novel conditional moment equations for a hybrid description. This unique collection of descriptions in a single toolbox facilitates the selection of appropriate modeling approaches. Unlike other software packages, the implementation of CERENA is completely general and allows, e.g., for time-dependent propensities and non mass action kinetics. By providing SBML import, symbolic model generation and simulation using MEX-files, CERENA is user-friendly and computationally efficient. The availability of forward and adjoint sensitivity analyses allows for further studies such as parameter estimation and uncertainty analysis. The MATLAB code implementing CERENA is freely available from http://cerenadevelopers.github.io/CERENA/. PMID- 26807912 TI - Ethnobotany and herbal medicine in modern complementary and alternative medicine: An overview of publications in the field of I&C medicine 2001-2013. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotanical knowledge and traditional medicinal practices from different parts of the world are of global importance and documentation of ethnobotanical, and ethnopharmacological data is a key prerequisite for further research in the area of herbal medicine and its implementation in clinical practice. AIMS: An attempt was made to evaluate the scientific output of research related to ethnobotany and herbal medicine in journals indexed in the subject area "Integrative and Complementary Medicine" in the period 2001-2013, in order to ascertain research trends in both subdisciplines. MATERIALS AND METHODS: All articles related to ethnobotany and herbal medicine, extracted from journals included in the field of I&C Medicine and published in the period 2001-2013, have been analyzed for general bibliometric data, and specific data: ethnobotanical data (geographic, floristic, pharmacological, sociological and other relevant data) and phytotherapeutic data (type of applied herbal medicine, plant species studied, pharmacological activity of studied plant species and disease and disorder type studied on a particular model). RESULTS: In the studied period, the number of articles dealing with ethnobotany and herbal medicine increased 6.3-fold. Articles related to ethnobotanical studies documented medicinal flora from 81 countries, either giving an overview of overall medicinal flora, or presenting the ethnomedicinal aspect of the use of plants for the treatment of ailments typical to the studied area. Additionally, the authors provided significant information on the methods of use and herbal preparations. In herbal medicine studies, plants, traditional plant remedies, herbal medicinal products and active herbal compounds were tested for many of pharmacological activities (146), with the curative activity emerging as most frequently tested. Out of 39 model systems, most of the studies were carried out under controlled in vitro conditions (4589 articles), followed by rat in vivo (2320), human in vivo (1285), mouse in vivo (955), and on agents of pathogenic diseases (887); more than 800 medical disorders were treated. CONCLUSIONS: The study revealed the regions most studied for new records of floristic and ethnomedicinal diversity, the most frequently studied plant species, and the most promising therapeutic indications for the integration of herbal remedies in the curative process, as ascertained from the selected bibliographic databases. PMID- 26807913 TI - Herb pairs containing Angelicae Sinensis Radix (Danggui): A review of bio-active constituents and compatibility effects. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Herb compatibility is one of the most important characteristics of traditional Chinese medicine (TCM). Rather than being used singly, Chinese herbs are often used in formulae to obtain synergistic effects or to diminish possible adverse reactions. Herb pair, the most fundamental and simplest form of multi-herb formulae, is a centralized representative of herb compatibility. Danggui (Angelicae Sinensis Radix), a widely used Chinese medicine, is usually combined with another herb to treat women's diseases in the clinic. A series of herb pairs containing Danggui have gradually become a focus of modern research, and they exhibit encouraging prospects for development. MATERIALS AND METHODS: A systematic search for studies related to herb pairs containing Danggui was performed via a library search (books, theses, reports, newspapers, magazines, and conference proceedings) and an electronic search (Web of Science, PubMed, and Google Scholar). These sources were scrutinized for information on Danggui herb pairs. RESULTS: Based on a previous statistical analysis, a database containing 16,529 formulae of Danggui from the "Dictionary of Traditional Chinese Medicine Formulae" was reviewed. The results showed a high frequency of compatibility between Danggui and other 22 herbs. The most common ratio among these chosen herb pairs was 1:1, and a majority of the pairs were applied for the treatment of diseases in internal medicine. The present paper reviews ethnopharmacology and advances in variations of the bio-active components and compatibility effects of the herb pairs containing Danggui, especially Danggui-Huangqi, Danggui-Chuanxiong, and Danggui-Shaoyao, which are used at high frequency. It was also observed that there were fewer studies of Danggui-Fuzi, Danggui-Huanglian, Danggui-Gancao, Danggui-Fangfeng and Danggui-Ganjiang, although they have been recorded in classical books as commonly used herb pairs. Moreover, some herb pairs such as Danggui-Niuxi and Danggui-Chaihu have been used at high frequency according to the statistical analysis, however, they were not recognized as herb pairs in many relevant books. CONCLUSIONS: Recently, several TCM researchers have become interested in investigating the bio-active constituents and compatibility effects of herb pairs. Thus, some methods for in depth study of herb pairs are essential to be established. The in vitro or in vivo bio-active constituents of herb pairs may differ from those of the single herbs. Additionally, comparative methods should be applied to study not only the bio-active constituents but also the effects of herb pairs. Study of component compatibility may be considered when the bio-active constituents and effects of an herb pair have been definitively demonstrated. Overall, the goal of our basic study of herb pairs should be their clinical application and the development of new drugs. PMID- 26807914 TI - A Serological Survey About Zoonoses in the Verkhoyansk Area, Northeastern Siberia (Sakha Republic, Russian Federation). AB - In 2012, a seroprevalence survey concerning 10 zoonoses, which were bacterial (Lyme borreliosis and Q fever), parasitic (alveolar echinococcosis [AE] and cystic echinococcosis [CE], cysticercosis, toxoplasmosis, toxocariasis, and trichinellosis), or arboviral (tick-borne encephalitis and West Nile virus infection), was conducted among 77 adult volunteers inhabiting Suordakh and Tomtor Arctic villages in the Verkhoyansk area (Yakutia). Following serological testing by enzyme-linked immunosorbent assay and/or western blot, no positive result was found for cysticercosis, CE, toxocariasis, trichinellosis, and both arboviral zoonoses. Four subjects (5.2%) had anti-Toxoplasma IgG, without the presence of specific IgM. More importantly, eight subjects (10.4%) tested positive for Lyme borreliosis, two (2.6%) for recently acquired Q fever, and one (1.3%) for AE. Lyme infection and Q fever, whose presence had not been reported so far in Arctic Yakutia, appeared therefore to be a major health threat for people dwelling, sporting, or working in the Arctic area of the Sakha Republic. PMID- 26807915 TI - Structure of bacterial respiratory complex I. AB - Complex I (NADH:ubiquinone oxidoreductase) plays a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation. It is the largest protein assembly of respiratory chains and one of the most elaborate redox membrane proteins known. Bacterial enzyme is about half the size of mitochondrial and thus provides its important "minimal" model. Dysfunction of mitochondrial complex I is implicated in many human neurodegenerative diseases. The L-shaped complex consists of a hydrophilic arm, where electron transfer occurs, and a membrane arm, where proton translocation takes place. We have solved the crystal structures of the hydrophilic domain of complex I from Thermus thermophilus, the membrane domain from Escherichia coli and recently of the intact, entire complex I from T. thermophilus (536 kDa, 16 subunits, 9 iron-sulphur clusters, 64 transmembrane helices). The 95A long electron transfer pathway through the enzyme proceeds from the primary electron acceptor flavin mononucleotide through seven conserved Fe-S clusters to the unusual elongated quinone-binding site at the interface with the membrane domain. Four putative proton translocation channels are found in the membrane domain, all linked by the central flexible axis containing charged residues. The redox energy of electron transfer is coupled to proton translocation by the as yet undefined mechanism proposed to involve long-range conformational changes. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt. PMID- 26807916 TI - Estimating the Incidence of Acute Infectious Intestinal Disease in the Community in the UK: A Retrospective Telephone Survey. AB - OBJECTIVES: To estimate the burden of intestinal infectious disease (IID) in the UK and determine whether disease burden estimations using a retrospective study design differ from those using a prospective study design. DESIGN/SETTING: A retrospective telephone survey undertaken in each of the four countries comprising the United Kingdom. Participants were randomly asked about illness either in the past 7 or 28 days. PARTICIPANTS: 14,813 individuals for all of whom we had a legible recording of their agreement to participate. OUTCOMES: Self reported IID, defined as loose stools or clinically significant vomiting lasting less than two weeks, in the absence of a known non-infectious cause. RESULTS: The rate of self-reported IID varied substantially depending on whether asked for illness in the previous 7 or 28 days. After standardising for age and sex, and adjusting for the number of interviews completed each month and the relative size of each UK country, the estimated rate of IID in the 7-day recall group was 1,530 cases per 1,000 person-years (95% CI: 1135-2113), while in the 28-day recall group it was 533 cases per 1,000 person-years (95% CI: 377-778). There was no significant variation in rates between the four countries. Rates in this study were also higher than in a related prospective study undertaken at the same time. CONCLUSIONS: The estimated burden of disease from IID varied dramatically depending on study design. Retrospective studies of IID give higher estimates of disease burden than prospective studies. Of retrospective studies longer recall periods give lower estimated rates than studies with short recall periods. Caution needs to be exercised when comparing studies of self-reported IID as small changes in study design or case definition can markedly affect estimated rates. PMID- 26807917 TI - Cottonseed Oil in Diets for Broilers in the Pre-Starter and Starter Phases. AB - The objective of this study was to evaluate the effect of different levels of crude cottonseed oil in isoenergetic diets, with or without supplementation of ferrous sulfate, on performance variables, relative weight of organs, and blood parameters of broilers, and on the economic viability of diets in the periods from 1 to 7 and 1 to 21 days of age. A total of 600 male birds of the Ross line were distributed in a completely randomized design in a (4*2) factorial arrangement with eight treatments (0, 2, 4, and 6% cottonseed oil with and without ferrous sulfate), and five replicates. The following variables were studied: feed intake, weight gain, feed conversion, weight of organs, blood parameters, and yield of carcass and cuts at 21 days. No effects of the levels of cottonseed oil were found on the performance of animals aged 1 to 7 days, or on the relative weights of the organs. In this same period, the weight gain, and the relative weights of heart, liver, and intestine of the animals that received ferrous sulfate were decreased, and feed conversion was worsened. In the period from 1 to 21 days, weight gain increased linearly with the increase in the levels of cottonseed oil. Blood parameters were not influenced by the diets. Crude cottonseed oil can be utilized in diets for broilers in the periods from 1 to 7 and 1 to 21 days of age at up to 6% of inclusion, and supplementation with ferrous sulfate is unnecessary if the differences in metabolization of the cottonseed oil are considered, with and without, it during the diet formulation process. PMID- 26807918 TI - How does the chemical potential of the substrate drive a uniporter? AB - Uniporters are a large class of transporters mediating facilitated diffusion of substrates along the direction of the substrate concentration gradient. Recently, structures of several important uniporters have been reported; however, the precise mechanisms of uniporter function remain subject of debate. Here, we present a series of general thermodynamic descriptions of uniporters, aimed at understanding the structure-function relationship of uniporters, and in particular to reconcile biochemical phenomena of uniporters with our previously proposed thermodynamic model of general transporters. PMID- 26807919 TI - Probing Ternary Solvent Effect in High V(oc) Polymer Solar Cells Using Advanced AFM Techniques. AB - This work describes a simple method to develop a high V(oc) low band gap PSCs. In addition, two new atomic force microscopy (AFM)-based nanoscale characterization techniques to study the surface morphology and physical properties of the structured active layer are introduced. With the help of ternary solvent processing of the active layer and C60 buffer layer, a bulk heterojunction PSC with V(oc) more than 0.9 V and conversion efficiency 7.5% is developed. In order to understand the fundamental properties of the materials ruling the performance of the PSCs tested, AFM-based nanoscale characterization techniques including Pulsed-Force-Mode AFM (PFM-AFM) and Mode-Synthesizing AFM (MSAFM) are introduced. Interestingly, MSAFM exhibits high sensitivity for direct visualization of the donor-acceptor phases in the active layer of the PSCs. Finally, conductive-AFM (cAFM) studies reveal local variations in conductivity in the donor and acceptor phases as well as a significant increase in photocurrent in the PTB7:ICBA sample obtained with the ternary solvent processing. PMID- 26807920 TI - The GATA3 gene is involved in leprosy susceptibility in Brazilian patients. AB - Leprosy outcome is a complex trait and the host-pathogen-environment interaction defines the emergence of the disease. Host genetic risk factors have been successfully associated to leprosy. The 10p13 chromosomal region was linked to leprosy in familial studies and GATA3 gene is a strong candidate to be part of this association. Here, we tested tag single nucleotide polymorphisms at GATA3 in two case-control samples from Brazil comprising a total of 1633 individuals using stepwise strategy. The A allele of rs10905284 marker was associated with leprosy resistance. Then, a functional analysis was conducted and showed that individuals carrying AA genotype express higher levels of GATA-3 protein in lymphocytes. So, we confirmed that the rs10905284 is a locus associated to leprosy and influences the levels of this transcription factor in the Brazilian population. PMID- 26807921 TI - First genome characterization of a novel hepatitis C virus genotype 5 variant. AB - We report a new hepatitis C virus (HCV) genotype 5 variant from a woman living in Burkina Faso. Phylogenetic analysis of the near full-length genome sequence suggests that this isolate HCV5_BF16 could be the first reported strain belonging to a new HCV 5 subtype, distinct from the 5a subtype. PMID- 26807922 TI - Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART. AB - Although Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, thus low abundance antiretroviral drug-resistant mutations (DRM's) at levels under limit of detection of conventional genotyping (<20% of quasispecies) could increase the risk of virologic failure. In this work, we analyzed the protease and reverse transcriptase regions of the pol gene by ultra-deep sequencing in pediatric patients under STI with the aim of determining the presence of high- and low abundance DRM's in the viral rebounds generated by the STI. High-abundance mutations in protease and high- and low-abundance mutations in reverse transcriptase were detected but no one of these are directly associated with resistance to antiretroviral drugs. The results could suggest that the evaluated STI program is virologically safe, but strict and carefully planned studies, with greater numbers of patients and interruption/restart cycles, are still needed to evaluate the selection of DRM's during STI. PMID- 26807923 TI - Elm Tree (Ulmus parvifolia) Bark Bioprocessed with Mycelia of Shiitake (Lentinus edodes) Mushrooms in Liquid Culture: Composition and Mechanism of Protection against Allergic Asthma in Mice. AB - Mushrooms can break down complex plant materials into smaller, more digestible and bioactive compounds. The present study investigated the antiasthma effect of an Ulmus parvifolia bark extract bioprocessed in Lentinus edodes liquid mycelium culture (BPUBE) against allergic asthma in chicken egg ovalbumin (OVA) sensitized/challenged mice. BPUBE suppressed total IgE release from U266B1 cells in a dose-dependent manner without cytotoxicity. Inhibitory activity of BPUBE against OVA-specific IgE secretion in bronchoalveolar lavage fluid (BALF) was observed in OVA-sensitized/challenged asthmatic mice. BPUBE also inhibited OVA specific IgG and IgG1 secretion into serum from the allergic mice, suggesting the restoration of a Th2-biased immune reaction to a Th1/Th2-balanced status, as indicated by the Th1/Th2 as well as regulatory T cell (Treg) cytokine profile changes caused by BPUBE in serum or BALF. Inflammatory cell counts in BALF and lung histology showed that leukocytosis and eosinophilia induced by OVA sensitization/challenge were inhibited by the oral administration of BPUBE. Amelioration of eosinophil infiltration near the trachea was associated with reduced eotaxin and vascular cell adhesion molecule-1 (VCAM-1) levels. Changes in proinflammatory mediator levels in BALF suggest that BPUBE decreased OVA sensitization-induced elevation of leukotriene C4 (LTC4) and prostaglandin D2 (PGD2). The finding that asthma-associated biomarker levels of OVA sensitized/challenged mice were much more inhibited with BPUBE treatment than NPUBE (not-bioprocessed Ulmus parvifolia extract) treatment suggested the production of new bioactive compounds by the mushroom mycelia that may be involved in enhancing the observed antiasthmatic properties. The possible relation of the composition determined by proximate analysis and GC/MS to observed bioactivity is discussed. The results suggest that the elm tree (Ulmus parvifolia) bark bioprocessed with mycelia of shiitake (Lentinus edodes) mushrooms has the potential to prevent and/or treat allergic asthma. PMID- 26807924 TI - Testosterone is Protective Against Cardiac Disease: Con. PMID- 26807925 TI - Predicting Risk of Chronic Renal Disease in Children with Vesicoureteral Reflux How Good or Bad are We Doing? PMID- 26807926 TI - Redefining Healthy Urine: A Cross-Sectional Exploratory Metagenomic Study of People With and Without Bladder Dysfunction. AB - PURPOSE: We used the PathoScope platform to perform species level analyses of publicly available, 16S rRNA pyrosequenced, asymptomatic urine data to determine relationships between microbiomes, and clinical and functional phenotypes. MATERIALS AND METHODS: We reanalyzed previously reported, cross-sectionally acquired urine samples from 47 asymptomatic subjects, including 23 controls and 24 subjects with neuropathic bladder. Urine was originally collected by the usual method of bladder drainage and analyzed by urinalysis, culture and pyrosequencing. Urinalysis and culture values were stratified as leukocyte esterase (0, or 1 or greater), nitrite (positive or negative), pyuria (fewer than 5, or 5 or greater white blood cells per high power field), cloudy urine (positive or negative) and urine culture bacterial growth (less than 50,000, or 50,000 or greater cfu/ml). PathoScope was used for next generation sequencing alignment, bacterial classification and microbial diversity characterization. RESULTS: Subjects with neuropathic bladder were significantly more likely to have positive leukocyte esterase and pyuria, cloudy urine and bacterial growth. Of 47 samples 23 showed bacterial growth on culture and in all samples bacteria were identified by pyrosequencing. Nonneuropathic bladder urine microbiomes included greater proportions of Lactobacillus crispatus in females and Staphylococcus haemolyticus in males. The Lactobacillus community differed significantly among females depending on bladder function. Irrespective of gender the subjects with neuropathic bladder had greater proportions of Enterococcus faecalis, Proteus mirabilis and Klebsiella pneumonia. In 4 subjects with neuropathic bladder Actinobaculum sp. was detected by sequencing and by PathoScope but not by cultivation and in all cases it was associated with pyuria. CONCLUSIONS: Using PathoScope plus 16S pyrosequencing we were able to identify unique, phenotype dependent, species level microbes. Novel findings included absent L. crispatus in the urine of females with neuropathic bladder and the presence of Actinobaculum only in subjects with neuropathic bladder. PMID- 26807927 TI - Is Ureteroscopy as Good as We Think? PMID- 26807928 TI - The Timing of Radical Cystectomy for bacillus Calmette-Guerin Failure: Comparison of Outcomes and Risk Factors for Prognosis. AB - PURPOSE: We compared the pathological and survival outcomes of patients who underwent radical cystectomy soon after bacillus Calmette-Guerin failure with those of patients who received additional salvage intravesical chemotherapy before cystectomy for nonmuscle invasive bladder cancer. We also identified predictors of prognosis in the entire cohort. MATERIALS AND METHODS: We retrospectively analyzed the records of 117 patients who underwent radical cystectomy for recurrent nonmuscle invasive bladder cancer at our institution from 1990 to 2012. The cohort was divided into group 1 of 61 patients treated only with bacillus Calmette-Guerin with or without interferon-alpha and group 2 of 56 who received at least 1 additional salvage intravesical chemotherapy after bacillus Calmette-Guerin. RESULTS: Final pathology and survival outcomes did not differ significantly between the groups. Five-year overall and cancer specific survival was similar in groups 1 and 2 at 80% and 85%, respectively, at approximately equivalent followups. Median bladder retention was 1.7 years longer in group 2 (p <0.001). On multivariate Cox regression analysis delayed cystectomy in group 2 did not convey a significant hazard for all cause mortality after cystectomy (HR 1.08, p = 0.808). Only up-staging to cT1 (HR 1.88, p = 0.045), lymph node invasion (HR 2.58, p = 0.023) and prostatic urethra involvement (HR 1.95, p = 0.029) achieved significance. CONCLUSIONS: With appropriate selection for salvage intravesical chemotherapy patients who elect bladder sparing treatment instead of earlier radical cystectomy after bacillus Calmette-Guerin fails do not sacrifice positive pathological or oncologic outcomes while retaining bladder function for a significantly longer duration. PMID- 26807929 TI - Testosterone is Protective against Cardiac Disease: Pro. PMID- 26807930 TI - In Vivo Dynamic Deformation of Articular Cartilage in Intact Joints Loaded by Controlled Muscular Contractions. AB - When synovial joints are loaded, the articular cartilage and the cells residing in it deform. Cartilage deformation has been related to structural tissue damage, and cell deformation has been associated with cell signalling and corresponding anabolic and catabolic responses. Despite the acknowledged importance of cartilage and cell deformation, there are no dynamic data on these measures from joints of live animals using muscular load application. Research in this area has typically been done using confined and unconfined loading configurations and indentation testing. These loading conditions can be well controlled and allow for accurate measurements of cartilage and cell deformations, but they have little to do with the contact mechanics occurring in a joint where non-congruent cartilage surfaces with different material and functional properties are pressed against each other by muscular forces. The aim of this study was to measure in vivo, real time articular cartilage deformations for precisely controlled static and dynamic muscular loading conditions in the knees of mice. Fifty and 80% of the maximal knee extensor muscular force (equivalent to approximately 0.4N and 0.6N) produced average peak articular cartilage strains of 10.5+/-1.0% and 18.3+/ 1.3% (Mean +/- SD), respectively, during 8s contractions. A sequence of 15 repeat, isometric muscular contractions (0.5s on, 3.5s off) of 50% and 80% of maximal muscular force produced cartilage strains of 3.0+/-1.1% and 9.6+/-1.5% (Mean +/- SD) on the femoral condyles of the mouse knee. Cartilage thickness recovery following mechanical compression was highly viscoelastic and took almost 50s following force removal in the static tests. PMID- 26807931 TI - Correction for human head motion in helical x-ray CT. AB - Correction for rigid object motion in helical CT can be achieved by reconstructing from a modified source-detector orbit, determined by the object motion during the scan. This ensures that all projections are consistent, but it does not guarantee that the projections are complete in the sense of being sufficient for exact reconstruction. We have previously shown with phantom measurements that motion-corrected helical CT scans can suffer from data insufficiency, in particular for severe motions and at high pitch. To study whether such data-insufficiency artefacts could also affect the motion-corrected CT images of patients undergoing head CT scans, we used an optical motion tracking system to record the head movements of 10 healthy volunteers while they executed each of the 4 different types of motion ('no', slight, moderate and severe) for 60 s. From these data we simulated 354 motion-affected CT scans of a voxelized human head phantom and reconstructed them with and without motion correction. For each simulation, motion-corrected (MC) images were compared with the motion-free reference, by visual inspection and with quantitative similarity metrics. Motion correction improved similarity metrics in all simulations. Of the 270 simulations performed with moderate or less motion, only 2 resulted in visible residual artefacts in the MC images. The maximum range of motion in these simulations would encompass that encountered in the vast majority of clinical scans. With severe motion, residual artefacts were observed in about 60% of the simulations. We also evaluated a new method of mapping local data sufficiency based on the degree to which Tuy's condition is locally satisfied, and observed that areas with high Tuy values corresponded to the locations of residual artefacts in the MC images. We conclude that our method can provide accurate and artefact-free MC images with most types of head motion likely to be encountered in CT imaging, provided that the motion can be accurately determined. PMID- 26807932 TI - Finding Meaning: HIV Self-Management and Wellbeing among People Taking Antiretroviral Therapy in Uganda. AB - The health of people living with HIV (PLWH) and the sustained success of antiretroviral therapy (ART) programmes depends on PLWH's motivation and ability to self-manage the condition over the long term, including adherence to drugs on a daily basis. PLWH's self-management of HIV and their wellbeing are likely to be interrelated. Successful self-management sustains wellbeing, and wellbeing is likely to motivate continued self-management. Detailed research is lacking on PLWH's self-management processes on ART in resource-limited settings. This paper presents findings from a study of PLWH's self-management and wellbeing in Wakiso District, Uganda. Thirty-eight PLWH (20 women, 18 men) were purposefully selected at ART facilities run by the government and by The AIDS Support Organisation in and around Entebbe. Two in-depth interviews were completed with each participant over three or four visits. Many were struggling economically, however the recovery of health and hope on ART had enhanced wellbeing and motivated self management. The majority were managing their condition well across three broad domains of self-management. First, they had mobilised resources, notably through good relationships with health workers. Advice and counselling had helped them to reconceptualise their condition and situation more positively and see hope for the future, motivating their work to self-manage. Many had also developed a new network of support through contacts they had developed at the ART clinic. Second, they had acquired knowledge and skills to manage their health, a useful framework to manage their condition and to live their life. Third, participants were psychologically adjusting to their condition and their new 'self': they saw HIV as a normal disease, were coping with stigma and had regained self-esteem, and were finding meaning in life. Our study demonstrates the centrality of social relationships and other non-medical aspects of wellbeing for self-management which ART programmes might explore further and encourage. PMID- 26807933 TI - Psycho-Socio-Economic Issues Challenging Multidrug Resistant Tuberculosis Patients: A Systematic Review. AB - BACKGROUND: Limited treatment options, long duration of treatment and associated toxicity adversely impact the physical and mental well-being of multidrug resistant tuberculosis (MDR-TB) patients. Despite research advances in the microbiological and clinical aspects of MDR-TB, research on the psychosocial context of MDR-TB is limited and less understood. METHODOLOGY: We searched the databases of PubMed, MEDLINE, Embase and Google Scholar to retrieve all published articles. The final manuscripts included in the review were those with a primary focus on psychosocial issues of MDR-TB patients. These were assessed and the information was thematically extracted on the study objective, methodology used, key findings, and their implications. Intervention studies were evaluated using components of the methodological and quality rating scale. Due to the limited number of studies and the multiple methodologies employed in the observational studies, we summarized these studies using a narrative approach, rather than conducting a formal meta-analysis. We used 'thematic synthesis' method for extracting qualitative evidences and systematically organised to broader descriptive themes. RESULTS: A total of 282 published articles were retrieved, of which 15 articles were chosen for full text review based on the inclusion criteria. Six were qualitative studies; one was a mixed methods study; and eight were quantitative studies. The included studies were divided into the following issues affecting MDR-TB patients: a) psychological issues b) social issues and economic issues c) psychosocial interventions. It was found that all studies have documented range of psychosocial and economic challenges experienced by MDR-TB patients. Depression, stigma, discrimination, side effects of the drugs causing psychological distress, and the financial constraints due to MDR-TB were some of the common issues reported in the studies. There were few intervention studies which addressed these psychosocial issues most of which were small pilot studies. There is dearth of large scale randomized psychosocial intervention studies that can be scaled up to strengthen management of MDR-TB patients which is crucial for the TB control programme. CONCLUSION: This review has captured the psychosocial and economic issues challenging MDR patients. However there is urgent need for feasible, innovative psychosocial and economic intervention studies that help to equip MDR-TB patients cope with their illness, improve treatment adherence, treatment outcomes and the overall quality of life of MDR-TB patients. PMID- 26807934 TI - Comparative photosynthetic and metabolic analyses reveal mechanism of improved cold stress tolerance in bermudagrass by exogenous melatonin. AB - Melatonin (N-acetyl-5-methoxytryptamine) has been reported to participate in plant development and abiotic stress responses. The main objective of this study was to investigate the role of melatonin in the cold-sensitive (S) and the cold tolerant (T) bermudagrass genotypes' response to cold stress. The genotypes were treated with 100 MUM melatonin and exposed to 4 degrees C temperature for 3 days. In both genotypes, cold stress increased the endogenous melatonin levels, and more prominently in T than S. Physiological responses indicated that exogenous melatonin triggered antioxidant activities in both genotypes, while it alleviated cell damage in the T genotype response to cold stress. Melatonin treatment under cold stress increased fluorescence curve levels for both genotypes, and higher in T than S genotypes. In both genotypes, the alterations in photosynthetic fluorescence parameters after melatonin treatment highlighted the participation of melatonin in improving photosystem response to cold stress, particularly for the cold-tolerant genotype. The metabolic analyses revealed the alterations of 44 cold-responsive metabolites in the two genotypes, mainly including carbohydrates, organic acids and amino acids. After exogenous melatonin treatment under cold condition, there was high accumulation of metabolites in the cold-tolerant regimes than their cold-sensitive counterparts. Collectively, the present study revealed differential modulations of melatonin between the cold sensitive and the cold-tolerant genotypes in response to cold stress. This was mainly by impacting antioxidant system, photosystem II, as well as metabolic homeostasis. PMID- 26807935 TI - Chloride stress triggers maturation and negatively affects the postharvest quality of persimmon fruit. Involvement of calyx ethylene production. AB - In recent years many hectares planted with persimmon trees in E Spain have been diagnosed with chloride toxicity. An effect of this abiotic stress on fruit quality has been reported in different crops. However, the impact of chloride stress on persimmon fruit quality is unknown. The harvest and postharvest quality of persimmons harvested from trees that manifest different intensities of chloride toxicity foliar symptoms was evaluated herein. Our results revealed that fruits from trees under chloride stress conditions underwent chloride accumulation in the calyx, which was more marked the greater the salt stress intensity trees were exposed to. Increased chloride concentrations in the calyx stimulated ethylene production in this tissue. In the fruits affected by slight and moderate chloride stress, calyx ethylene production accelerated the maturity process, as reflected by increased fruit colour and diminished fruit firmness. In the fruits under severe chloride stress, the high ethylene levels in the calyx triggered autocatalytic ethylene production in other fruit tissues, which led fruit maturity to drastically advance. In these fruits effectiveness of CO2 deastringency treatment was not complete and fruit softening enhanced during the postharvest period. Moreover, chloride stress conditions had a marked effect on reducing fruit weight, even in slightly stressed trees. PMID- 26807936 TI - The effects of mariculture on heavy metal distribution in sediments and cultured fish around the Pearl River Delta region, south China. AB - Thirty-six sediment samples were collected from six mariculture sites and corresponding reference sites (approximately 200-300 m away from each mariculture site) to study the effects of mariculture on heavy metal: copper (Cu), zinc (Zn), chromium (Cr) and lead (Pb) distribution in sediments and cultured fish around the Pearl River Delta region, south China. The mean concentrations of Cu, Zn, Cr and Pb in all mariculture sediment samples were 109, 273, 99 and 33 mg/kg, compared with 63, 209, 56 and 23 mg/kg for reference sediment samples, respectively. The Pollution Load Index of sediment for each site was over 1, implying substantial heavy metal pollution. The results of principal component analysis and hierarchical clustering analysis indicate that marine aquaculture activities have enriched the surface sediments underneath mariculture rafts with Cu, Zn and Pb, possibly due to the accumulation of unconsumed fish feeds, fish excreta and antifouling paints (except Cr). Two kinds of fish feeds, feed pellets and trash fish commonly used in Hong Kong were analyzed. The concentrations of Zn and Cu contained in feed pellets were significantly higher (p < 0.05) than in trash fish due to addition of these elements as growth promoters during pellet production. However, the Pb content in trash fish (due to contamination) was significantly higher (p < 0.05) than in feed pellets. Three cultured fish species, namely red snapper (Lutjanus campechanus), orange-spotted grouper (Epinephelus coioides) and snubnose pompano (Trachinotus blochii), were collected from each mariculture site for metal analysis. Lead concentrations in 21 fish samples exceeded the Chinese safety guideline (0.5 mg/kg, GB18406.4-2001), indicating that Pb contamination in cultured fish would be a public health concern. PMID- 26807937 TI - Effects of nickel exposure on testicular function, oxidative stress, and male reproductive dysfunction in Spodoptera litura Fabricius. AB - Nickel is an environmental pollutant that adversely affects the male reproductive system. In the present study, the effects of nickel exposure on Spodoptera litura Fabricius were investigated by feeding larvae artificial diets containing different doses of nickel for three generations. Damage to testes and effects on male reproduction were examined. The amount of nickel that accumulated in the testes of newly emerged males increased as the nickel dose in the diet increased during a single generation. Nickel exposure increased the amount of thiobarbituric acid reactive substances and decreased the amount of glutathione in treatment groups compared with the control. The activity levels of the antioxidant response indices superoxide dismutases, catalase, and glutathione peroxidase in the testes showed variable dose-dependent relationships with nickel doses and duration of exposure. Nickel doses also disrupted the development of the testes by decreasing the weight and volume of testes and the number of eupyrene and apyrene sperm bundles in treatment groups compared with the control. When the nickel-treated males mated with normal females, fecundity was inhibited by the higher nickel doses in all three generations, but fecundity significantly increased during the second generation, which received 5 mg kg(-1) nickel. Hatching rates in all treatments significantly decreased in a dose-dependent manner in the three successive generations. The effects of nickel on these parameters correlated with the duration of nickel exposure. Results indicate assays of testes may be a novel and efficient means of evaluating the effects of heavy metals on phytophagous insects in an agricultural environment. PMID- 26807938 TI - Bacterial reduction of highly concentrated perchlorate: Kinetics and influence of co-existing electron acceptors, temperature, pH and electron donors. AB - Perchlorate reduction kinetics and effects of various environmental conditions on removal of perchlorate from synthetic water were investigated to seek high strength perchlorate removal using mixed perchlorate reducing bacteria. Results demonstrated that perchlorate (50-1500 mg L(-1)) could be degraded rapidly within 28 h under the optimal conditions. The maximum specific perchlorate reduction rate (qmax) and half saturation constant (Ks) were 0.92 mg-perchlorate (mg-dry weight)(-1) h(-1) and 157.7 mg L(-1), respectively. In the ClO4(-)-NO3(-) systems obvious but recoverable lags were caused in perchlorate reduction and the lag time increased with the ratio of nitrate to perchlorate concentration increasing from 0.5 to 3. While in the ClO4(-)-SO4(2-) systems inhibitions didn't occur until the ratio of sulfate to perchlorate concentration exceeded 10. The optimum temperature and pH value were 35 degrees C and 6.85, respectively. The optimal acetate-to-perchlorate ratio that could consume all perchlorate and acetate simultaneously was about 2. Dechloromonas, one of the most prominent perchlorate reducing bacteria, was identified as the dominant bacterium in the acclimated culture (69.33% of the whole clones). The study demonstrated that the perchlorate acclimated mixed microorganisms can readily and efficiently realize reduction of highly concentrated perchlorate in wastewater. PMID- 26807939 TI - Concentrations of legacy and emerging flame retardants in air and soil on a transect in the UK West Midlands. AB - Passive air samples were collected monthly for 6 months from 8 sites along a transect of Birmingham, United Kingdom between June 2012 and January 2013. Soil samples were collected once at each site. Average concentrations of BDE-209, SigmaPBDEs17:183 and SigmaPBDEs in ambient air were 150, 49, and 180 pg m(-3), respectively. Atmospheric concentrations of PBDEs were negatively correlated with distance from the city centre, exhibiting an "urban pulse". The average SigmaHBCDD air concentration was 100 pg m(-3), however concentrations were not correlated with distance from the city centre. Several emerging flame retardants (EFRs) were identified in air and/or soil samples: 2,3,4,5-tetrabromo-bis(2 ethylhexyl) phthalate (BEH-TEBP), 1,2-dibromo-4-(1,2 dibromoethyl)cyclohexane (TBECH or DBE-DBCH), allyl 2,4,6-tribromophenyl ether (ATE), 2-bromoallyl 2,4,6 tribromophenyl ether (BATE), decabromodiphenyl ethane (DBDPE), and dechlorane plus (DP or DDC-CO). Average concentrations of BDE-209, SigmaPBDEs17:183 and SigmaPBDEs in soil were 11, 3.6, and 15 ng g(-1) soil organic matter. PBDE concentrations in soil were higher at sites closest to the city centre, however correlations with distance from the city centre were not significant. BDEs-47 and -99 contributed more to SigmaPBDEs in soil samples than air samples, but in both, the predominant congener was BDE-209. BATE was more abundant in air than soil but ATE was abundant in soil but not air. PMID- 26807940 TI - Freeze-drying as suitable method to achieve ready-to-use yeast biosensors for androgenic and estrogenic compounds. AB - Recombinant yeast assays (RYAs) have been proved to be a suitable tool for the fast screening of compounds with endocrine disrupting activities. However, ready to-use versions more accessible to less equipped laboratories and field studies are scarce and far from optimal throughputs. Here, we have applied freeze-drying technology to optimize RYA for the fast assessment of environmental compounds with estrogenic and androgenic potencies. The effects of different cryoprotectants, initial optical density and long-term storage were evaluated. The study included detailed characterization of sensitivity, robustness and reproducibility of the new ready-to-use versions, as well as comparison with the standard assays. Freeze-dried RYAs showed similar dose-responses curves to their homolog standard assays, with Lowest Observed Effect Concentration (LOEC) and Median effective Concentration (EC50) of 1 nM and 7.5 nM for testosterone, and 0.05 nM and 0.5 nM for 17beta-estradiol, respectively. Freeze-dried cells stored at 4 degrees C retained maximum sensitivity up to 2 months, while cells stored at -18 degrees C showed no decrease in sensitivity throughout the study (10 months). This ready-to-use RYA is easily accessible and may be potentially used for on-site applications. PMID- 26807941 TI - Historical trends of anthropogenic metals in Eastern Tibetan Plateau as reconstructed from alpine lake sediments over the last century. AB - Reconstructing trace metal historical trends are essential for better understanding anthropogenic impact on remote alpine ecosystems. We present results from an alpine lake sediment from the Eastern Tibetan Plateau to decipher the accumulation history of cadmium (Cd), lead (Pb) and zinc (Zn) over last century, from the preindustrial to the modern period. Cd, Pb and Zn in the sediment of Caohaizi Lake clearly suffered from atmospheric deposition, and the mining and smelting were regarded as the main anthropogenic sources. Since the mid-1990s, over 80% of trace metals were quantified from anthropogenic emissions. The temporal trends of anthropogenic metal fluxes showed that the contamination history of Pb was earlier than that of Cd and Zn, which was in agreement with the regional Pb emission history, but lagged behind the Pb decline in Europe and North America. The fluxes of anthropogenic Cd and Zn were relatively constant until the 1980s, increased sharply between the 1980s and the mid-1990s, and then kept the high values. The anthropogenic fluxes of Pb showed a marked rise around 1950, and increased sharply in the 1980s. In the mid-1990s, this flux reached the peak, and then decreased gradually. The Pb deposition flux at present in comparison with other lake records in the areas of Tibetan Plateau further demonstrated that trace metals in the Caohaizi Lake region were probably from Southwest China and South Asia. Economic development in these regions still puts pressure on the remote alpine ecosystems, and thus the impact of trace metals merits more attention. PMID- 26807942 TI - Optimizing the combined application of amendments to allow plant growth in a multielement-contaminated soil. AB - This study was aimed to 1) properly understand the dynamics of toxic elements (Al, Fe, Mn, Cu, Pb, Zn and As) in a sulphide-mine soil after combined application of compost from urban sewage sludge (SVC) and bottom ashes from biomass combustion (BA) and to 2) optimize the combination of both amendments for vegetation growth. Soil was amended following a D-optimal design and the mixtures (15 in total) were incubated during 30 d. At the end of the incubation, the effects of amendments on the assessed variables as well as the process modelling were evaluated by Response Surface Methodology (RSM). The process modelling confirmed that quadratic models were adequate to explain the behaviour of the assessed variables (R(2) >= 0.94 and Q(2) >= 0.75). Both amendments significantly increased pH and electrical conductivity, while reduced metal extractability. A different behaviour of As respect to metals was observed and high doses of BA sharply increased its extractability. The optimization process indicated that adequate conditions for vegetation growth would be reached adding the soil with 6.8% of SVC and 3.1% of BA (dry weight). After amendments application the germination and root elongation of three energy crops were significantly increased while lipid peroxidation was decreased. Therefore, the combined application of SVC and BA to a contaminated soil could improve soil conditions and might be expected to have an advantage during plant growth. Moreover, the RSM could be a powerful technique for the assessment of combined amendment effects on soil properties and their effective application in multielement-contaminated soils. PMID- 26807943 TI - Enhanced sequestration of Cr(VI) by nanoscale zero-valent iron supported on layered double hydroxide by batch and XAFS study. AB - Herein, the reduction of nanoscale zero-valent iron (NZVI) and adsorption of layered double hydroxides (LDH) to sequester Cr(VI) were well combined by the immobilization of NZVI onto LDH surface (NZVI/LDH). The characterization results revealed that LDH decreased NZVI aggregation and thus increased Cr(VI) sequestration. The batch results indicated that Cr(VI) sequestration by NZVI/LDH was higher than that of NZVI, and superior to the sum of reduction and adsorption. The LDH with good anion exchange property allowed the adsorption of Cr(VI), facilitating interfacial reaction by increasing the local concentration of Cr(VI) in the NZVI vicinity. X-ray absorption near edge structure (XANES) results indicated that Cr(VI) was almost completely reduced to Cr(III) by NZVI/LDH, but Cr(VI) was partly reduced to Cr(III) by NZVI with a trace of Cr(VI) adsorbed on corrosion products. The coordination environment of Cr from extended X-ray absorption fine structure (EXAFS) analysis revealed that LDH could be a good scavenger for the insoluble products produced during reaction. So, the insoluble products on NZVI could be reduced, and its reactivity could be maintained. These results demonstrated that NZVI/LDH exhibits multiple functionalities relevant to the remediation of Cr(VI)-contaminated sites. PMID- 26807944 TI - Use of orbitrap-MS/MS and QSAR analyses to estimate mutagenic transformation products of iopamidol generated during ozonation and chlorination. AB - The effects of two water purification processes (ozonation, and chlorination after ozonation) on the mutagenicity of a solution containing iopamidol (X-ray contrast medium) were investigated by using the Ames assay. No mutagenicity was observed during ozonation. In contrast, mutagenicity was induced by the ozone treated iopamidol-containing solution after subsequent chlorination, indicating that mutagenic transformation-products (TPs) were generated. Ten of 70 peaks detected on the LC/MS total ion chromatogram (TIC) of the ozone-treated iopamidol containing solution after chlorination had a positive correlation (r(2) > 0.6) between their peak areas and the observed mutagenicity, suggesting that TPs detected as these peaks may induce mutagenicity. To narrow down the possible contributors to the observed mutagenicity, we compared the areas of the peaks on the TIC-charts with and without chlorination. Of the ten peaks, six were also detected in the ozone-treated iopamidol-containing solution without chlorination, which did not induce mutagenicity, indicating that these peaks were not related to the observed mutagenicity. Accurate m/z values and MS/MS analysis with an orbitrap MS of the remaining four peaks revealed that two of them represented the same TP in the negative and positive ion modes. The three remaining TPs were assessed in four quantitative structure-activity relationship models for predicting Ames mutagenicity. At least one model predicted that two of the three TPs were mutagenic, whereas none of the models predicted that the other TP was a mutagen, suggesting that the former TPs, estimated as N1-acetyl-5-amino-6-chloro 2-iodobenzene-1,3-dicarboxamide and 3-hydroxy-2-{3-[(2-hydroxyethoxy)carbonyl] 2,4,6-triiodo-5-nitrobenzoyl}amino)propanoic acid, could be the candidate compounds that contributed to the observed mutagenicity. PMID- 26807945 TI - Evaluation of the toxicity of ionic liquids on trypsin: A mechanism study. AB - The toxicity of ionic liquids (ILs) was evaluated by using trypsin as biomarker. Experimental results indicated that the trypsin activity was inhibited by ILs and the degree of inhibition highly depended on the chemical structures of ILs. Primary analysis illustrated that hydrophobicity of ILs was one of the driven forces ruling the ILs-trypsin interaction. Thermodynamic parameters, Gibbs free energy change (DeltaG), enthalpy change (DeltaH) and entropy change (DeltaS) were obtained by analyzing the fluorescence behavior of trypsin in the presence of ILs. Both negative DeltaH and DeltaS suggested hydrogen bonding was the major driven force underlying the IL-trypsin interaction. To assess the toxicity of ILs, it should be considered the combination of the hydrogen bonding ability and hydrophobicity of ILs. A regression based model was established to correlate the relationship of the inhibitory ability, hydrophobicity and hydrogen bonding ability of ILs. PMID- 26807946 TI - Heavy metals in soils from a typical county in Shanxi Province, China: Levels, sources and spatial distribution. AB - The concentrations of As, Cd, Cr, Cu, Pb, Ni, Zn, and Hg in 128 surface soil samples from Xiangfen County, Shanxi Province, China were measured. The concentrations of these eight heavy metals were lower than the critical values in the national soil quality standard. However, these concentrations were found to be slightly higher than their background values in soils in Shanxi Province, indicating enrichment of these metals in soils in Xiangfen County, especially for Hg and Cd. Principal component analysis coupled with cluster analysis was used to analyze the data and identify possible sources of these heavy metals; the results showed that the eight heavy metals in soils from Xiangfen County came from three different sources. Lead, Cd, Cu and Zn mainly arose from agricultural practices and vehicle emissions. Arsenic and Ni arose mainly from parent materials. Industrial practices were the main sources of Cr and Hg. The spatial distribution of the heavy metals varied greatly, and was closely correlated to local anthropogenic activities. This study will be helpful not only for improving local soil environmental quality but will also provide a basis for effectively targeting policies to protect soils from long-term heavy metal accumulation. PMID- 26807947 TI - Simulation of the transfer and fate of gamma-HCH in epikarst system. AB - The thin surface soil layer and karst features in karst terrains lead to poor filtration, poor pre-purification and rapid infiltration, so that karst groundwater systems are particularly vulnerable to contamination. Due to its extensive use in past, gamma-hexachlorocyclohexane (gamma-HCH) is ubiquitous in various environmental compartments of China, even though it has been prohibited since 1984. However, very little is known about its movement and behavior in special karst system. In this study, a dynamic fugacity model was established for gamma-HCH in epikarst system via dividing the karst soil into multiple layers coupled with the physical-chemical properties of gamma-HCH. The simulated results in soil profile were in good agreement with the measured values of gamma-HCH. The modeled results predict that only 18 g gamma-HCH will be left in the studied area in 2020, which is only 0.4% of the largest reserves in 1983, and about 99.99% of gamma-HCH will remains in soil. The concentrations of gamma-HCH in air, plant and 0-20 cm layer soil in the studied area descended quickly after HCHs was prohibited in 1984, while its concentration in soil layer deeper than 20 cm (deeper soil) increased continuously till 1997. The dominant transfer process of gamma-HCH between the adjacent compartments in the studied area was from 0-20 cm layer to the deeper soil. Sensitivity analysis results showed that emission rate, infiltration coefficient, total organic carbon of soil, degradation rate in soil, compartment area and volume were the top six influential parameters for predicting gamma-HCH concentration. PMID- 26807948 TI - Directed Assembly of Single Wall Carbon Nanotube Field Effect Transistors. AB - The outstanding electronic properties of single wall carbon nanotubes (SWCNTs) have made them prime candidates for future nanoelectronics technologies. One of the main obstacles to the implementation of advanced SWCNT electronics to date is the inability to arrange them in a manner suitable for complex circuits. Directed assembly of SWCNT segments onto lithographically patterned and chemically functionalized substrates is a promising way to organize SWCNTs in topologies that are amenable to integration for advanced applications, but the placement and orientational control required have not yet been demonstrated. We have developed a technique for assembling length sorted and chirality monodisperse DNA-wrapped SWCNT segments on hydrophilic lines patterned on a passivated oxidized silicon substrate. Placement of individual SWCNT segments at predetermined locations was achieved with nanometer accuracy. Three terminal electronic devices, consisting of a single SWCNT segment placed either beneath or on top of metallic source/drain electrodes were fabricated. Devices made with semiconducting nanotubes behaved as typical p-type field effect transistors (FETs), whereas devices made with metallic nanotubes had a finite resistance with little or no gate modulation. This scalable, high resolution approach represents an important step forward toward the potential implementation of complex SWCNT devices and circuits. PMID- 26807949 TI - A Modern Approach to the Surgical Treatment of Gastroesophageal Reflux Disease. AB - Gastroesophageal reflux disease (GERD) is a common disorder that can cause a variety of typical and atypical symptoms. Although most patients can be rendered asymptomatic with medical treatment, some experience persistent breakthrough symptoms. A long history of GERD is associated with the risk for the development of Barrett's esophagus and ultimately esophageal carcinoma. Although often underutilized, minimally invasive antireflux surgery can help manage these patients. However, thorough evaluation and accurate diagnosis of GERD and its underlying pathophysiology are critical in ensuring successful surgical treatment. This review offers a stepwise approach to the diagnostic workup of GERD and how to appropriately tailor available surgical treatments to specific patient subgroups. PMID- 26807950 TI - Separate circuitries encode the hedonic and nutritional values of sugar. AB - Sugar exerts its potent reinforcing effects via both gustatory and post-ingestive pathways. It is, however, unknown whether sweetness and nutritional signals engage segregated brain networks to motivate ingestion. We found in mice that separate basal ganglia circuitries mediated the hedonic and nutritional actions of sugar. During sugar intake, suppressing hedonic value inhibited dopamine release in ventral, but not dorsal, striatum, whereas suppressing nutritional value inhibited dopamine release in dorsal, but not ventral, striatum. Consistently, cell-specific ablation of dopamine-excitable cells in dorsal, but not ventral, striatum inhibited sugar's ability to drive the ingestion of unpalatable solutions. Conversely, optogenetic stimulation of dopamine-excitable cells in dorsal, but not ventral, striatum substituted for sugar in its ability to drive the ingestion of unpalatable solutions. Our data indicate that sugar recruits a distributed dopamine-excitable striatal circuitry that acts to prioritize energy-seeking over taste quality. PMID- 26807951 TI - Epigenomic annotation of gene regulatory alterations during evolution of the primate brain. AB - Although genome sequencing has identified numerous noncoding alterations between primate species, which of those are regulatory and potentially relevant to the evolution of the human brain is unclear. Here we annotated cis-regulatory elements (CREs) in the human, rhesus macaque and chimpanzee genomes using chromatin immunoprecipitation followed by sequencing (ChIP-seq) in different anatomical regions of the adult brain. We found high similarity in the genomic positioning of rhesus macaque and human CREs, suggesting that the majority of these elements were already present in a common ancestor 25 million years ago. Most of the observed regulatory changes between humans and rhesus macaques occurred before the ancestral separation of humans and chimpanzees, leaving a modest set of regulatory elements with predicted human specificity. Our data refine previous predictions and hypotheses on the consequences of genomic changes between primate species and allow the identification of regulatory alterations relevant to the evolution of the brain. PMID- 26807952 TI - PV plasticity sustained through D1/5 dopamine signaling required for long-term memory consolidation. AB - Long-term consolidation of memories depends on processes occurring many hours after acquisition. Whether this involves plasticity that is specifically required for long-term consolidation remains unclear. We found that learning-induced plasticity of local parvalbumin (PV) basket cells was specifically required for long-term, but not short/intermediate-term, memory consolidation in mice. PV plasticity, which involves changes in PV and GAD67 expression and connectivity onto PV neurons, was regulated by cAMP signaling in PV neurons. Following induction, PV plasticity depended on local D1/5 dopamine receptor signaling at 0 5 h to regulate its magnitude, and at 12-14 h for its continuance, ensuring memory consolidation. D1/5 dopamine receptor activation selectively induced DARPP 32 and ERK phosphorylation in PV neurons. At 12-14 h, PV plasticity was required for enhanced sharp-wave ripple densities and c-Fos expression in pyramidal neurons. Our results reveal general network mechanisms of long-term memory consolidation that requires plasticity of PV basket cells induced after acquisition and sustained subsequently through D1/5 receptor signaling. PMID- 26807953 TI - HCN1 Channels Enhance Rod System Responsivity in the Retina under Conditions of Light Exposure. AB - PURPOSE: Vision originates in rods and cones at the outer retina. Already at these early stages, diverse processing schemes shape and enhance image information to permit perception over a wide range of lighting conditions. In this work, we address the role of hyperpolarization-activated and cyclic nucleotide-gated channels 1 (HCN1) in rod photoreceptors for the enhancement of rod system responsivity under conditions of light exposure. METHODS: To isolate HCN1 channel actions in rod system responses, we generated double mutant mice by crossbreeding Hcn1-/- mice with Cnga3-/- mice in which cones are non-functional. Retinal function in the resulting Hcn1-/- Cnga3-/- animals was followed by means of electroretinography (ERG) up to the age of four month. Retinal imaging via scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) was also performed to exclude potential morphological alterations. RESULTS: This study on Hcn1-/- Cnga3-/- mutant mice complements our previous work on HCN1 channel function in the retina. We show here in a functional rod-only setting that rod responses following bright light exposure terminate without the counteraction of HCN channels much later than normal. The resulting sustained signal elevation does saturate the retinal network due to an intensity-dependent reduction in the dynamic range. In addition, the lack of rapid adaptational feedback modulation of rod photoreceptor output via HCN1 in this double mutant limits the ability to follow repetitive (flicker) stimuli, particularly under mesopic conditions. CONCLUSIONS: This work corroborates the hypothesis that, in the absence of HCN1-mediated feedback, the amplitude of rod signals remains at high levels for a prolonged period of time, leading to saturation of the retinal pathways. Our results demonstrate the importance of HCN1 channels for regular vision. PMID- 26807954 TI - Correction: fMiRNA-192 and miRNA-204 Directly Suppress lncRNA HOTTIP and Interrupt GLS1-Mediated Glutaminolysis in Hepatocellular Carcinoma. AB - [This corrects the article DOI: 10.1371/journal.pgen.1005726.]. PMID- 26807956 TI - Effect of animal-assisted interventions on depression, agitation and quality of life in nursing home residents suffering from cognitive impairment or dementia: a cluster randomized controlled trial. AB - OBJECTIVES: The prevalence of neuropsychiatric symptoms in cognitively impaired nursing home residents is known to be very high, with depression and agitation being the most common symptoms. The possible effects of a 12-week intervention with animal-assisted activities (AAA) in nursing homes were studied. The primary outcomes related to depression, agitation and quality of life (QoL). METHOD: A prospective, cluster randomized multicentre trial with a follow-up measurement 3 months after end of intervention was used. Inclusion criteria were men and women aged 65 years or older, with a diagnosis of dementia or having a cognitive deficit. Ten nursing homes were randomized to either AAA with a dog or a control group with treatment as usual. In total, 58 participants were recruited: 28 in the intervention group and 30 in the control group. The intervention consisted of a 30-min session with AAA twice weekly for 12 weeks in groups of three to six participants, led by a qualified dog handler. Norwegian versions of the Cornell Scale for Depression, the Brief Agitation Rating Scale and the Quality of Life in Late-stage Dementia scale were used. RESULTS: A significant effect on depression and QoL was found for participants with severe dementia at follow-up. For QoL, a significant effect of AAA was also found immediately after the intervention. No effects on agitation were found. CONCLUSIONS: Animal-assisted activities may have a positive effect on symptoms of depression and QoL in older people with dementia, especially those in a late stage. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26807955 TI - Ceramide Induces Human Hepcidin Gene Transcription through JAK/STAT3 Pathway. AB - Changes in lipid metabolism and iron content are observed in the livers of patients with fatty liver disease. The expression of hepcidin, an iron-regulatory and acute phase protein synthesized by the liver, is also modulated. The potential interaction of lipid and iron metabolism is largely unknown. We investigated the role of lipid intermediate, ceramide in the regulation of human hepcidin gene, HAMP. Human hepatoma HepG2 cells were treated with cell-permeable ceramide analogs. Ceramide induced significant up-regulation of HAMP mRNA expression in HepG2 cells. The effect of ceramide on HAMP expression was mediated through transcriptional mechanisms because it was completely blocked with actinomycin D treatment. Reporter assays also confirmed the activation of 0.6 kb HAMP promoter by ceramide. HepG2 cells treated with ceramide displayed increased phosphorylation of STAT3, JNK, and NF-kappaB proteins. However, ceramide induced the binding of STAT3, but not NF-kappaB or c-Jun, to HAMP promoter, as shown by the chromatin immunoprecipitation assays. The mutation of STAT3 response element within 0.6 kb HAMP promoter region significantly inhibited the stimulatory effect of ceramide on HAMP promoter activity. Similarly, the inhibition of STAT3 with a pan-JAK kinase inhibitor and STAT3 siRNA pool also diminished the induction of both HAMP promoter activity and mRNA expression by ceramide. In conclusion, we have shown a direct role for ceramide in the activation of hepatic HAMP transcription via STAT3. Our findings suggest a crosstalk between lipid and iron metabolism in the liver, which may contribute to the pathogenesis of obesity related fatty liver disease. PMID- 26807957 TI - Chlamydia trachomatis Frequency in a Cohort of HPV-Infected Colombian Women. AB - BACKGROUND: Chlamydia trachomatis (C. trachomatis), an obligate intracellular bacterium, is the commonest infectious bacterial agent of sexual transmission throughout the world. It has been shown that the presence of this bacteria in the cervix represents a risk regarding HPV persistence and, thereafter, in developing cervical cancer (CC). Prevalence rates may vary from 2% to 17% in asymptomatic females, depending on the population being analysed. This study reports the identification of C. trachomatis in a cohort of 219 HPV-infected Colombian females. METHODS: C. trachomatis infection frequency was determined during each of the study's follow-up visits; it was detected by amplifying the cryptic plasmid sequence by polymerase chain reaction (PCR) using two sets of primers: KL5/KL6 and KL1/KL2. Infection was defined as a positive PCR result using either set of primers at any time during the study. Cox proportional risk models were used for evaluating the association between the appearance of infection and a group of independent variables. RESULTS: Base line C. trachomatis infection frequency was 28% (n = 61). Most females infected by C. trachomatis were infected by multiple types of HPV (77.42%), greater prevalence occurring in females infected with HPV-16 (19.18%), followed by HPV-58 (17.81%). It was observed that females having had the most sexual partners (HR = 6.44: 1.59-26.05 95%CI) or infection with multiple types of HPV (HR = 2.85: 1.22-6.63 95%CI) had the greatest risk of developing C. trachomatis. CONCLUSIONS: The study provides data regarding the epidemiology of C. trachomatis /HPV coinfection in different population groups of Colombian females and contributes towards understanding the natural history of C. trachomatis infection. PMID- 26807958 TI - Population Genetic Structure and Reproductive Strategy of the Introduced Grass Centotheca lappacea in Tropical Land-Use Systems in Sumatra. AB - Intensive transformation of lowland rainforest into oil palm and rubber monocultures is the most common land-use practice in Sumatra (Indonesia), accompanied by invasion of weeds. In the Jambi province, Centotheca lappacea is one of the most abundant alien grass species in plantations and in jungle rubber (an extensively used agroforest), but largely missing in natural rainforests. Here, we investigated putative genetic differentiation and signatures for adaptation in the introduced area. We studied reproductive mode and ploidy level as putative factors for invasiveness of the species. We sampled 19 populations in oil palm and rubber monocultures and in jungle rubber in two regions (Bukit Duabelas and Harapan). Amplified fragment length polymorphisms (AFLP) revealed a high diversity of individual genotypes and only a weak differentiation among populations (FST = 0.173) and between the two regions (FST = 0.065). There was no significant genetic differentiation between the three land-use systems. The metapopulation of C. lappacea consists of five genetic partitions with high levels of admixture; all partitions appeared in both regions, but with different proportions. Within the Bukit Duabelas region we observed significant isolation by-distance. Nine AFLP loci (5.3% of all loci) were under natural diversifying selection. All studied populations of C. lappacea were diploid, outcrossing and self-incompatible, without any hints of apomixis. The estimated residence time of c. 100 years coincides with the onset of rubber and oil palm planting in Sumatra. In the colonization process, the species is already in a phase of establishment, which may be enhanced by efficient selection acting on a highly diverse gene pool. In the land-use systems, seed dispersal might be enhanced by adhesive spikelets. At present, the abundance of established populations in intensively managed land-use systems might provide opportunities for rapid dispersal of C. lappacea across rural landscapes in Sumatra, while the invasion potential in rainforest ecosystems appears to be moderate as long as they remain undisturbed. PMID- 26807959 TI - How toxic is ibogaine? AB - CONTEXT: Ibogaine is a psychoactive indole alkaloid found in the African rainforest shrub Tabernanthe Iboga. It is unlicensed but used in the treatment of drug and alcohol addiction. However, reports of ibogaine's toxicity are cause for concern. OBJECTIVES: To review ibogaine's pharmacokinetics and pharmacodynamics, mechanisms of action and reported toxicity. METHODS: A search of the literature available on PubMed was done, using the keywords "ibogaine" and "noribogaine". The search criteria were "mechanism of action", "pharmacokinetics", "pharmacodynamics", "neurotransmitters", "toxicology", "toxicity", "cardiac", "neurotoxic", "human data", "animal data", "addiction", "anti-addictive", "withdrawal", "death" and "fatalities". The searches identified 382 unique references, of which 156 involved human data. Further research revealed 14 detailed toxicological case reports. PHARMACOKINETICS AND PHARMACODYNAMICS: Ibogaine is metabolized mainly by CYP2D6 to the primary metabolite noribogaine (10-hydroxyibogamine). Noribogaine is present in clinically relevant concentrations for days, long after ibogaine has been cleared. MECHANISMS OF ACTION: Ibogaine and noribogaine interact with multiple neurotransmitter systems. They show micromolar affinity for N-methyl-D-aspartate (NMDA), kappa- and MU opioid receptors and sigma-2 receptor sites. Furthermore, ibogaine has been shown to interact with the acetylcholine, serotonin and dopamine systems; it alters the expression of several proteins including substance P, brain-derived neurotrophic factor (BDNF), c-fos and egr-1. NEUROTOXICITY: Neurodegeneration was shown in rats, probably mediated by stimulation of the inferior olive, which has excitotoxic effects on Purkinje cells in the cerebellum. Neurotoxic effects of ibogaine may not be directly relevant to its anti-addictive properties, as no signs of neurotoxicity were found following doses lower than 25 mg/kg intra peritoneal in rats. Noribogaine might be less neurotoxic than ibogaine. CARDIOTOXICITY: Ether-a-go-go-related gene (hERG) potassium channels in the heart might play a crucial role in ibogaine's cardiotoxicity, as hERG channels are vital in the repolarization phase of cardiac action potentials and blockade by ibogaine delays this repolarization, resulting in QT (time interval between the start of the Q wave and the end of the T wave in the electrical cycle of the heart) interval prolongation and, subsequently, in arrhythmias and sudden cardiac arrest. Twenty-seven fatalities have been reported following the ingestion of ibogaine, and pre-existing cardiovascular conditions have been implicated in the death of individuals for which post-mortem data were available. However, in this review, 8 case reports are presented which suggest that ibogaine caused ventricular tachyarrhythmias and prolongation of the QT interval in individuals without any pre-existing cardiovascular condition or family history. Noribogaine appears at least as harmful to cardiac functioning as ibogaine. TOXICITY FROM DRUG-DRUG INTERACTION: Polymorphism in the CYP2D6 enzyme can influence blood concentrations of both ibogaine and its primary metabolite, which may have implications when a patient is taking other medication that is subject to significant CYP2D6 metabolism. CONCLUSIONS: Alternative therapists and drug users are still using iboga extract, root scrapings, and ibogaine hydrochloride to treat drug addiction. With limited medical supervision, these are risky experiments and more ibogaine-related deaths are likely to occur, particularly in those with pre-existing cardiac conditions and those taking concurrent medications. PMID- 26807960 TI - Hybrid Coordination Networks Constructed from E-Keggin-Type Polyoxometalates and Rigid Imidazole-Based Bridging Ligands as New Carriers for Noble-Metal Catalysts. AB - Three hybrid coordination networks that were constructed from E-Keggin polyoxometalate building units and imidazole-based bridging ligands were prepared under hydrothermal conditions, that is, H[(Hbimb)2 (bimb){Zn4 PMo(V8) Mo(VI) 4O40}]?6 H2O(1), [Zn(Hbimbp)(bimbp)3 {Zn4 PMo(V8) Mo(VI) 4O40}]?DMF?3.5 H2O(2), and H[Zn2 (timb)2 (bimba)2 Cl2 {Zn4 PMo(V8) Mo(VI) 4O40}]?7 H2O(3) (bimb=1,4 bis(1-imidazolyl)benzene, bimbp=4,4'-bis(imidazolyl)biphenyl, timb=1,3,5-tris(1 imidazolyl)benzene, bimba=3,5-bis(1-imidazolyl)benzenamine). All three compounds were characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, and single-crystal X-ray diffraction. The mixed valence of the Mo centers was analyzed by XPS spectroscopy and bond-valence sum calculations. In all three compounds, the E-Keggin polyoxometalate (POM) units acted as nodes that were connected by rigid imidazole-based bridging ligands to form hybrid coordination networks. In compound 1, 1D zigzag chains extended to form a 3D supramolecular architecture through intermolecular hydrogen-bonding interactions. Compound 2 consisted of 2D curved sheets, whilst compound 3 contained chiral 2D networks. Because of the intrinsic reducing properties of E-Keggin POM species, noble-metal nanoparticles were loaded onto these POM-based coordination networks. Thus, compounds 1-3 were successfully loaded with Ag nanoparticles, and the corresponding composite materials exhibited high catalytic activities for the reduction of 4-nitrophenol. PMID- 26807961 TI - Neo-adjuvant chemotherapy plus surgery versus surgery alone for cervical cancer: Meta-analysis of randomized controlled trials. AB - The aim of this study was to evaluate the efficacy and safety of neo-adjuvant chemotherapy (NACT) versus radical surgery (RS) for patients with cervical cancer. A meta-analysis of randomized controlled trials (RCT) of NACT + RS versus RS alone for patients with cervical cancer was performed according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta analyses (PRISMA) statement. The following electronic databases were searched from their inception to April 2015: PUBMED, EMBASE and Cochrane Library. Statistical analysis was done using REVIEW MANAGER 5.3. Five RCT involving 739 patients were studied. There were significant differences between the NACT + RS and the RS-alone groups for positive lymph nodes (OR, 0.45; 95%CI: 0.29-0.70) and parametrial infiltration (OR, 0.48; 95% CI: 0.25-0.92), while treatment efficacy did not differ significantly for 5-year overall survival rate (OR, 1.17; 95% CI: 0.85-1.61), 5-year disease-free survival rate (OR, 1.09; 95% CI: 0.77-1.56) or recurrence rate (OR, 1.17; 95% CI: 0.85-1.61). The results also indicated that chemotherapy-related toxicity was well tolerated. For patients with cervical cancer, NACT could significantly reduce the number of positive lymph nodes and the level of parametrial infiltration compared with RS alone, and be well tolerated. PMID- 26807962 TI - Combined large-cell neuroendocrine carcinoma and endometrioid adenocarcinoma of the endometrium: A case report and survey of related literature. AB - Primary large-cell neuroendocrine carcinoma of the endometrium is extremely rare and has a poor prognosis. This report describes a case of combined large-cell neuroendocrine carcinoma and endometrioid adenocarcinoma of the endometrium diagnosed as stage IIIA. The patient underwent surgery and chemotherapy and has been well with no evidence of disease for 20 months. The optimal treatment for this rare tumor has not been established. Considering its rarity and variability, it is difficult to establish an evidence-based therapeutic regimen. PMID- 26807963 TI - Non-Peutz-Jeghers syndrome-associated ovarian sex cord tumor with annular tubules: Report of a malignant case. AB - A sex cord tumor with annular tubules (SCTAT) is a rare but distinctive subtype of sex cord stromal tumor of the ovary. Its clinical features depend on an association with Peutz-Jeghers syndrome (PJS). SCTAT associated with PJS typically manifests as bilateral, multifocal, and small lesions and is clinically benign. In contrast, SCTAT not associated with PJS often manifests as a unilateral large mass and 20% of such tumors have malignant potential. Most patients with SCTAT are diagnosed at stage I, and metastasis is rare. Here we present a case of malignant SCTAT of stage III A1(ii) (retroperitoneal lymph node metastasis, largest dimension of metastasis >10 mm) in a 14-year-old girl without PJS. PMID- 26807964 TI - New perspectives on nanotechnology and antiretroviral drugs: a 'small' solution for a big promise in HIV treatment? PMID- 26807966 TI - c-SRC protein tyrosine kinase regulates early HIV-1 infection post-entry. AB - OBJECTIVE: We investigated whether HIV-1 inhibition by SRC-family kinase inhibitors is through the non-receptor tyrosine kinase pp60 (c-SRC) and its binding partner, protein tyrosine kinase 2 beta (PTK2B). DESIGN: CD4 T lymphocytes were infected with R5 (JR-FL) or X4 (HXB2) HIV-1. We used SRC-family kinase inhibitors or targeted siRNA knockdown of c-SRC and PTK2B, then monitored effects on the early HIV-1 lifecycle. METHODS: Four SRC-family kinase inhibitors or targeted siRNA knockdown were used to reduce c-SRC or PTK2B protein expression. Activated CD4 T-lymphocytes were infected with recombinant, nef deficient, or replication-competent infectious viruses. Knockdown experiments examined early infection by monitoring: luciferase activity, expression of host surface receptors, reverse transcriptase activity, p24 levels and qPCR of reverse transcripts, integrated HIV-1, and two-long terminal repeat (2-LTR) circles. RESULTS: All SRC-family kinase inhibitors inhibited R5 and X4 HIV-1 infection. Neither c-SRC nor PTK2B siRNA knockdown had an effect on cell surface receptors (CD4, CXCR4, and CCR5) nor on reverse transcriptase activity. However, using JR FL both decreased luciferase activity while increasing late reverse transcripts (16-fold) and 2-LTR circles (eight-fold) while also decreasing viral integration (four-fold). With HXB2, c-SRC but not PTK2B siRNA knockdown produced similar results. CONCLUSIONS: Our results suggest c-SRC tyrosine kinase is a major regulator of HIV-1 infection, participating in multiple stages of infection post entry: Reduced proviral integration with increased 2-LTR circles is reminiscent of integrase inhibitors used in combination antiretroviral therapy. Decreasing c SRC expression and/or activity provides a new target for antiviral intervention and the potential for repurposing existing FDA-approved kinase inhibitors. PMID- 26807965 TI - Mitochondrial injury and cognitive function in HIV infection and methamphetamine use. AB - OBJECTIVE: In this work, we evaluated the association of human immunodeficiency virus (HIV) infection and methamphetamine (METH) use with mitochondrial injury in the brain and its implication on neurocognitive impairment. DESIGN: Mitochondria carry their genome (mtDNA) and play a critical role in cellular processes in the central nervous system. METH is commonly used in HIV-infected populations. HIV infection and METH use can cause damage to mtDNA and lead to neurocognitive morbidity. We evaluated HIV infection and METH use with mitochondrial injury in the brain. METHODS: We obtained white and gray matter from Brodmann areas 7, 8, 9, 46 of the following: HIV-infected individuals with history of past METH use (HIV+METH+, n = 16), HIV-infected individuals with no history of past METH use (HIV+METH-, n = 11), and HIV-negative controls (HIV-METH-, n = 30). We used the 'common deletion', a 4977 bp mutation, as a measurement of mitochondrial injury, and quantified levels of mtDNA and 'common deletion' by droplet digital PCR, and evaluated in relation to neurocognitive functioning [Global Deficit Score (GDS)]. RESULTS: Levels of mtDNA and mitochondrial injury were highest in white matter of Brodmann area 46. A higher relative proportion of mtDNA carrying the 'common deletion' was associated with lower GDS (P < 0.01) in HIV+METH+ but higher GDS (P < 0.01) in HIV+METH-. CONCLUSIONS: Increased mitochondrial injury was associated with worse neurocognitive function in HIV+METH- individuals. Among HIV+METH+ individuals, an opposite effect was seen. PMID- 26807967 TI - The Meanings in the messages: how SMS reminders and real-time adherence monitoring improve antiretroviral therapy adherence in rural Uganda. AB - OBJECTIVE: To understand how a pilot intervention combining SMS reminders with real-time adherence monitoring improved adherence to HIV antiretroviral therapy (ART) for adults initiating treatment in rural Uganda. DESIGN: Qualitative study, conducted with a pilot randomized controlled trial. METHODS: Sixty-two pilot intervention study participants took part in qualitative interviews on: preferences for content; frequency and timing of SMS adherence reminders; understandings and experiences of SMS reminders; and understandings and experiences of real-time adherence monitoring. Analysis of interview data was inductive and derived categories describing how participants experienced the intervention, and what it meant to them. RESULTS: SMS reminders prompted taking individual doses of antiretroviral therapy, and helped to develop a 'habit' of adherence. Real-time adherence monitoring was experienced as 'being seen'; participants interpreted 'being seen' as an opportunity to demonstrate seriousness of commitment to treatment and 'taking responsibility' for adherence. Both SMS reminders and real-time monitoring were interpreted as signs of 'caring' by the healthcare system. Feeling 'cared about' offset depressed mood and invigorated adherence. CONCLUSION: Although serving as reminders, SMS messages and real-time adherence monitoring also had larger emotional and moral meanings for participants that they felt improved their adherence. Understanding the larger 'meanings in the messages,' as well as their more literal content and function, will be central in delineating how SMS reminders and other adherence interventions using cellular technology work or do not work in varying contexts. PMID- 26807968 TI - Treatment options after virological failure of first-line tenofovir-based regimens in South Africa: an analysis by deep sequencing. AB - In a South African cohort of participants living with HIV developing virological failure on first-line tenofovir disoproxyl fumarate (TDF)-based regimens, at least 70% of participants demonstrated TDF resistance according to combined Sanger and MiSeq genotyping. Sanger sequencing missed the K65R mutation in 30% of samples. Unless HIV genotyping is available to closely monitor epidemiological HIV resistance to TDF, its efficacy as second-line therapy will be greatly compromised. PMID- 26807969 TI - Ensuring quality: a key consideration in scaling-up HIV-related point-of-care testing programs. AB - OBJECTIVE: The objective of the WHO/US President's Emergency Plan for AIDS Relief consultation was to discuss innovative strategies, offer guidance, and develop a comprehensive policy framework for implementing quality-assured HIV-related point of-care testing (POCT). METHODS: The consultation was attended by representatives from international agencies (WHO, UNICEF, UNITAID, Clinton Health Access Initiative), United States Agency for International Development, Centers for Disease Control and Prevention/President's Emergency Plan for AIDS Relief Cooperative Agreement Partners, and experts from more than 25 countries, including policy makers, clinicians, laboratory experts, and program implementers. MAIN OUTCOMES: There was strong consensus among all participants that ensuring access to quality of POCT represents one of the key challenges for the success of HIV prevention, treatment, and care programs. The following four strategies were recommended: implement a newly proposed concept of a sustainable quality assurance cycle that includes careful planning; definition of goals and targets; timely implementation; continuous monitoring; improvements and adjustments, where necessary; and a detailed evaluation; the importance of supporting a cadre of workers [e.g. volunteer quality corps (Q-Corps)] with the role to ensure that the quality assurance cycle is followed and sustained; implementation of the new strategy should be seen as a step-wise process, supported by development of appropriate policies and tools; and joint partnership under the leadership of the ministries of health to ensure sustainability of implementing novel approaches. CONCLUSION: The outcomes of this consultation have been well received by program implementers in the field. The recommendations also laid the groundwork for developing key policy and quality documents for the implementation of HIV-related POCT. PMID- 26807970 TI - Human papilloma virus prevalence in HIV patients with head and neck squamous cell carcinoma. AB - OBJECTIVE: The implication of human papilloma virus (HPV) in head and neck squamous cell carcinoma (HNSCC) is well established, especially in oropharyngeal SCC. HIV patients have a higher risk of persistent HPV infection. We investigated the role of HPV in HNSCC carcinogenesis in HIV population. DESIGN: Retrospective monocentric study. METHODS: We studied HIV patients who presented with HNSCC between 1994 and 2014. For each patient, tumor characteristics, HIV disease, and survival information were collected. Tumor HPV testing was performed using p16 immunohistochemistry (IHC), in-situ hybridization and PCR. We assessed the percentage of HPV in this population of HIV patients with HNSCC and compared HIV disease characteristics based on HPV status. RESULTS: Forty-seven patients were included: 11 women/36 men, the median age was 50 years. Tumor HPV testing was performed in 40 patients. Tumors were located in oropharynx (32%), oral cavity (32%), larynx (21%), and hypopharynx (11%). At the time of diagnosis, median CD4 level was 385 cells/MUl, 31% of the patients were stage (Centers for Disease Control, stage C). The percentage of HPV linked to HNSCC for all locations in HIV patients was 30% (n = 12). HPV16 accounted for 50% of all HPV genotypes. HPV positive status was associated with a CD4 nadir of less than 200 (P = 0.026), but not with CD4 level at time of diagnosis (P = 0.414). HPV-negative tumors tend to be associated with poorer 5-year overall survival (hazard ratio = 2.9, P = 0.0711). CONCLUSION: HPV plays a critical role in HNSCC development in HIV population. HIV immunodeficiency may increase HPV persistence and progression of HNSCC. PMID- 26807972 TI - Hypovitaminosis D and hyperparathyroidism: effects on bone turnover and bone mineral density among perinatally HIV-infected adolescents. AB - OBJECTIVES: The impact of hypovitaminosis D and secondary hyperparathyroidism on bone mineral density (BMD) in the setting of pediatric HIV infection remains unclear. This study aimed to determine the prevalence of hypovitaminosis D and hyperparathyroidism and their effects on bone turnover and BMD among HIV-infected adolescents in Southeast Asia. DESIGN: A multicenter, cross-sectional study evaluating bone health and vitamin D metabolism in HIV-infected adolescents in Thailand and Indonesia. METHODS: Perinatally HIV-infected adolescents aged 10-18 years on antiretroviral therapy with virologic suppression were enrolled. Serum 25-hydroxyvitamin D, intact parathyroid hormone, and bone turnover markers (C terminal cross-linked telopeptide of type I collagen and procollagen type I amino terminal propeptide) were assessed; serum 25-hydroxyvitamin D less than 20 ng/ml and intact parathyroid hormone more than 65 pg/ml were defined as hypovitaminosis D and hyperparathyroidism, respectively. Lumbar spine (L2-L4) BMD Z-score -2 or less was defined as low BMD. RESULTS: Of 394 adolescents, 57% were women. The median age [interquartile range (IQR)] was 15.0 (13.3-16.9) years. The prevalence of hypovitaminosis D, hyperparathyroidism, and both conditions were 21% [95% confidence interval (CI): 17-25%], 17% (95% CI: 13-20%), and 5% (95% CI: 3-7%), respectively. Adolescents with hypovitaminosis D and secondary hyperparathyroidism had the highest median bone resorption (C-terminal cross linked telopeptide of type I collagen: 1610 vs. 1270 ng/l; P = 0.04) and bone formation (procollagen type I amino-terminal propeptide: 572 vs. 330 MUg/l; P = 0.02) markers, and the greatest proportion of low BMD (42 vs. 15%; P = 0.01) compared with the rest of the cohort. CONCLUSION: Hypovitaminosis D complicated with secondary hyperparathyroidism was associated with increased bone turnover and bone loss. Early treatment of hypovitaminosis D before hyperparathyroidism occurs may be important to prevent bone mass deterioration. PMID- 26807971 TI - Persistence of integrated HIV DNA in CXCR3 + CCR6 + memory CD4+ T cells in HIV infected individuals on antiretroviral therapy. AB - BACKGROUND: HIV latent infection can be established in vitro by treating resting CD4 T cells with chemokines that bind to chemokine receptors (CKR), CCR7, CXCR3, and CCR6, highly expressed on T cells. OBJECTIVE: To determine if CKR identify CD4 T cells enriched for HIV in HIV-infected individuals receiving suppressive antiretroviral therapy (ART). DESIGN: A cross-sectional study of CKR expression and HIV persistence in blood from HIV-infected individuals on suppressive ART for more than 3 years (n = 48). A subset of 20 individuals underwent leukapheresis and sorting of specific CD4 T-cell subsets. METHODS: We used flow cytometry to quantify CCR5, CCR6, CXCR3, and CXCR5 expression on CD4 T cells. HIV persistence was quantified using real-time Polymerase Chain Reaction to detect total, integrated HIV DNA, 2-long terminal repeat circles and cell-associated unspliced (CA-US) HIV RNA in total CD4 T cells from blood or sorted T-cell subsets. Associations between CKR and HIV persistence in CD4 T cells in blood were determined using regression models and adjusted for current and nadir CD4 T-cell counts. RESULTS: The frequency of cells harbouring integrated HIV DNA was inversely associated with current CD4 T-cell count and positively associated with CCR5+ CD4 T cells, CXCR3+CCR6+ and CXCR3+CCR6- expression on total memory CD4 T cells (P < 0.001, 0.048, 0.015, and 0.016, respectively). CXCR3+CCR6+ CM CD4 T cells contained the highest amount of integrated HIV DNA and lowest ratio of CA US HIV RNA to DNA compared to all T-cell subsets examined. CONCLUSION: CXCR3 and CCR6 coexpression defines a subset of CD4 T cells that are preferentially enriched for HIV DNA in HIV-infected individuals on ART. PMID- 26807973 TI - How many people are living with undiagnosed HIV infection? An estimate for Italy, based on surveillance data. AB - OBJECTIVE: To estimate the size and characteristics of the undiagnosed HIV population in Italy in 2012 applying a method that does not require surveillance data from the beginning of the HIV epidemic. METHODS: We adapted the method known as 'London method 2'; the undiagnosed population is estimated as the ratio between the estimated annual number of simultaneous HIV/clinical AIDS diagnoses and the expected annual progression rate to clinical AIDS in the undiagnosed HIV population; the latter is estimated using the CD4+ cell count distribution of asymptomatic patients reported to surveillance. Under-reporting/ascertainment of new diagnoses was also considered. Also, the total number of people living with HIV was estimated. RESULTS: The undiagnosed HIV population in 2012 was 13,729 (95% confidence interval: 12,152-15,592), 15,102 (13,366-17,151) and 16,475 (14,581-18,710), assuming no under-reporting/ascertainment, 10 and 20% of under reporting/ascertainment, respectively. The percentage of undiagnosed cases was higher among HIV people aged below 25 years (25-28%), MSM (16-19%) and people born abroad (16-19%), whereas it was small among injection drug users (3%). CONCLUSION: The estimate of people in Italy with undiagnosed HIV in 2012 was in a plausible range of 12,000-18,000 cases, corresponding to 11-13% of the overall prevalence. The method is straightforward to implement only requiring annual information from the HIV surveillance system about CD4+ cell count and clinical stage at HIV diagnosis. Thus, it could be used to monitor if a certain prevention initiative lead to the reduction of the undiagnosed HIV population over time. It can also be easily implemented in other countries collecting the same basic information from the HIV surveillance system. PMID- 26807974 TI - "Trees Live on Soil and Sunshine!"--Coexistence of Scientific and Alternative Conception of Tree Assimilation. AB - Successful learning is the integration of new knowledge into existing schemes, leading to an integrated and correct scientific conception. By contrast, the co existence of scientific and alternative conceptions may indicate a fragmented knowledge profile. Every learner is unique and thus carries an individual set of preconceptions before classroom engagement due to prior experiences. Hence, instructors and teachers have to consider the heterogeneous knowledge profiles of their class when teaching. However, determinants of fragmented knowledge profiles are not well understood yet, which may hamper a development of adapted teaching schemes. We used a questionnaire-based approach to assess conceptual knowledge of tree assimilation and wood synthesis surveying 885 students of four educational levels: 6th graders, 10th graders, natural science freshmen and other academic studies freshmen. We analysed the influence of learner's characteristics such as educational level, age and sex on the coexistence of scientific and alternative conceptions. Within all subsamples well-known alternative conceptions regarding tree assimilation and wood synthesis coexisted with correct scientific ones. For example, students describe trees to be living on "soil and sunshine", representing scientific knowledge of photosynthesis mingled with an alternative conception of trees eating like animals. Fragmented knowledge profiles occurred in all subsamples, but our models showed that improved education and age foster knowledge integration. Sex had almost no influence on the existing scientific conceptions and evolution of knowledge integration. Consequently, complex biological issues such as tree assimilation and wood synthesis need specific support e.g. through repeated learning units in class- and seminar-rooms in order to help especially young students to handle and overcome common alternative conceptions and appropriately integrate scientific conceptions into their knowledge profile. PMID- 26807975 TI - A Murine Model of Candida glabrata Vaginitis Shows No Evidence of an Inflammatory Immunopathogenic Response. AB - Candida glabrata is the second most common organism isolated from women with vulvovaginal candidiasis (VVC), particularly in women with uncontrolled diabetes mellitus. However, mechanisms involved in the pathogenesis of C. glabrata associated VVC are unknown and have not been studied at any depth in animal models. The objective of this study was to evaluate host responses to infection following efforts to optimize a murine model of C. glabrata VVC. For this, various designs were evaluated for consistent experimental vaginal colonization (i.e., type 1 and type 2 diabetic mice, exogenous estrogen, varying inocula, and co-infection with C. albicans). Upon model optimization, vaginal fungal burden and polymorphonuclear neutrophil (PMN) recruitment were assessed longitudinally over 21 days post-inoculation, together with vaginal concentrations of IL-1beta, S100A8 alarmin, lactate dehydrogenase (LDH), and in vivo biofilm formation. Consistent and sustained vaginal colonization with C. glabrata was achieved in estrogenized streptozotocin-induced type 1 diabetic mice. Vaginal PMN infiltration was consistently low, with IL-1beta, S100A8, and LDH concentrations similar to uninoculated mice. Biofilm formation was not detected in vivo, and co infection with C. albicans did not induce synergistic immunopathogenic effects. This data suggests that experimental vaginal colonization of C. glabrata is not associated with an inflammatory immunopathogenic response or biofilm formation. PMID- 26807976 TI - Working Alliance in Internet-Based Cognitive-Behavioral Therapy for Obsessive Compulsive Disorder. PMID- 26807977 TI - Minimum size for a nanoscale temperature discriminator based on a thermochemical system. AB - What are the limits of size reduction for information processing devices based on chemical reactions? In this paper, we partially answer this question. We show that a thermochemical system can be used to design a discriminator of the parameters associated with oscillations of the ambient temperature. Depending on the amplitude and frequency of the oscillations, the system exhibits sharp transitions between different types of its time evolutions. This phenomenon can be used to discriminate between different parameter values describing the oscillating environment. We investigate the reliability of the thermochemical discriminator as a function of the number of molecules involved in the reactions. A stochastic model of chemical reactions and heat exchange with the neighborhood, in which the number of molecules explicitly appears, is introduced. For the selected values of the parameters, thermochemical discriminators operating with less than 10(5) molecules appear to be unreliable. PMID- 26807978 TI - Immune checkpoint blockade in lymphoid malignancies. AB - Malignant cells may subvert and escape endogenous host immune surveillance by up regulation of immune inhibitory signals known as immune checkpoints. These checkpoints are important therapeutic targets, and antibodies that block checkpoint signaling have shown remarkable efficacy in some solid tumors as well as in some refractory hematologic malignancies. In hematologic cancers, the mechanism of these checkpoints is complex, as the tumor and immune system are one and the same. In this review, we evaluate the biology of checkpoint inhibition, review the current data on its efficacy in lymphoid tumors, and explore uncertainties in the field, including those involving the precise mechanisms of action, the appropriate timing of therapy, and the differences in response rate between lymphoid tumor types. PMID- 26807979 TI - Comparative Study of the Effect of Sample Pretreatment and Extraction on the Determination of Flavonoids from Lemon (Citrus limon). AB - BACKGROUND: Flavonoids have shown to exert multiple beneficial effects on human health, being also appreciated by both food and pharmaceutical industries. Citrus fruits are a key source of flavonoids, thus promoting studies to obtain them. Characteristics of these studies are the discrepancies among sample pretreatments and among extraction methods, and also the scant number of comparative studies developed so far. OBJECTIVE: Evaluate the effect of both the sample pretreatment and the extraction method on the profile of flavonoids isolated from lemon. RESULTS: Extracts from fresh, lyophilized and air-dried samples obtained by shaking extraction (SE), ultrasound-assisted extraction (USAE), microwave assisted extraction (MAE) and superheated liquid extraction (SHLE) were analyzed by LC-QTOF MS/MS, and 32 flavonoids were tentatively identified using MS/MS information. ANOVA applied to the data from fresh and dehydrated samples and from extraction by the different methods revealed that 26 and 32 flavonoids, respectively, were significant (p<=0.01). The pairwise comparison (Tukey HSD; p<=0.01) showed that lyophilized samples are more different from fresh samples than from air-dried samples; also, principal component analysis (PCA) showed a clear discrimination among sample pretreatment strategies and suggested that such differences are mainly created by the abundance of major flavonoids. On the other hand, pairwise comparison of extraction methods revealed that USAE and MAE provided quite similar extracts, being SHLE extracts different from the other two. In this case, PCA showed a clear discrimination among extraction methods, and their position in the scores plot suggests a lower abundance of flavonoids in the extracts from SHLE. In the two PCA the loadings plots revealed a trend to forming groups according to flavonoid aglycones. CONCLUSIONS: The present study shows clear discrimination caused by both sample pretreatments and extraction methods. Under the studied conditions, liophilization provides extracts with higher amounts of flavonoids, and USAE is the best method for isolation of these compounds, followed by MAE and SE. On the contrary, the SHLE method was the less favorable to extract flavonoids from citrus owing to degradation. PMID- 26807980 TI - Ribosomal Synthesis of Peptides with Multiple beta-Amino Acids. AB - The compatibility of beta-amino acids with ribosomal translation was studied for decades, but it has been still unclear whether the ribosome can accept various beta-amino acids, and whether the ribosome can introduce multiple beta-amino acids in a peptide. In the present study, by using the Escherichia coli reconstituted cell-free translation system with a reprogramed genetic code, we screened beta-amino acids that give high single incorporation efficiency and used them to synthesize peptides containing multiple beta-amino acids. The experiments of single beta-amino acid incorporation into a peptide revealed that 13 beta amino acids are compatible with ribosomal translation. Six of the tested beta amino acids (betahGly, l-betahAla, l-betahGln, l-betahPhg, l-betahMet, and d betahPhg) showed high incorporation efficiencies, and seven (l-betahLeu, l betahIle, l-betahAsn, l-betahPhe, l-betahLys, d-betahAla, and d-betahLeu) showed moderate incorporation efficiencies; whereas no full-length peptide was produced using other beta-amino acids (l-betahPro, l-betahTrp, and l-betahGlu). Subsequent double-incorporation experiments using beta-amino acids with high single incorporation efficiency revealed that elongation of peptides with successive beta-amino acids is prohibited. Efficiency of the double-incorporation of the beta-amino acids was restored by the insertion of Tyr or Ile between the two beta amino acids. On the basis of these experiments, we also designed mRNA sequences of peptides, and demonstrated the ribosomal synthesis of peptides containing different types of beta-amino acids at multiple positions. PMID- 26807981 TI - Alcohol Dehydrogenase Protects against Endoplasmic Reticulum Stress-Induced Myocardial Contractile Dysfunction via Attenuation of Oxidative Stress and Autophagy: Role of PTEN-Akt-mTOR Signaling. AB - BACKGROUND: The endoplasmic reticulum (ER) plays an essential role in ensuring proper folding of the newly synthesized proteins. Aberrant ER homeostasis triggers ER stress and development of cardiovascular diseases. ADH is involved in catalyzing ethanol to acetaldehyde although its role in cardiovascular diseases other than ethanol metabolism still remains elusive. This study was designed to examine the impact of ADH on ER stress-induced cardiac anomalies and underlying mechanisms involved using cardiac-specific overexpression of alcohol dehydrogenase (ADH). METHODS: ADH and wild-type FVB mice were subjected to the ER stress inducer tunicamycin (1 mg/kg, i.p., for 48 hrs). Myocardial mechanical and intracellular Ca(2+) properties, ER stress, autophagy and associated cell signaling molecules were evaluated. RESULTS: ER stress compromised cardiac contractile function (evidenced as reduced fractional shortening, peak shortening, maximal velocity of shortening/relengthening, prolonged relengthening duration and impaired intracellular Ca(2+) homeostasis), oxidative stress and upregulated autophagy (increased LC3B, Atg5, Atg7 and p62), along with dephosphorylation of PTEN, Akt and mTOR, all of which were attenuated by ADH. In vitro study revealed that ER stress-induced cardiomyocyte anomaly was abrogated by ADH overexpression or autophagy inhibition using 3-MA. Interestingly, the beneficial effect of ADH was obliterated by autophagy induction, inhibition of Akt and mTOR. ER stress also promoted phosphorylation of the stress signaling ERK and JNK, the effect of which was unaffected by ADH transgene. CONCLUSIONS: Taken together, these findings suggested that ADH protects against ER stress-induced cardiac anomalies possibly via attenuation of oxidative stress and PTEN/Akt/mTOR pathway-regulated autophagy. PMID- 26807982 TI - Comparative Study of Injury Models for Studying Muscle Regeneration in Mice. AB - BACKGROUND: A longstanding goal in regenerative medicine is to reconstitute functional tissues or organs after injury or disease. Attention has focused on the identification and relative contribution of tissue specific stem cells to the regeneration process. Relatively little is known about how the physiological process is regulated by other tissue constituents. Numerous injury models are used to investigate tissue regeneration, however, these models are often poorly understood. Specifically, for skeletal muscle regeneration several models are reported in the literature, yet the relative impact on muscle physiology and the distinct cells types have not been extensively characterised. METHODS: We have used transgenic Tg:Pax7nGFP and Flk1GFP/+ mouse models to respectively count the number of muscle stem (satellite) cells (SC) and number/shape of vessels by confocal microscopy. We performed histological and immunostainings to assess the differences in the key regeneration steps. Infiltration of immune cells, chemokines and cytokines production was assessed in vivo by Luminex(r). RESULTS: We compared the 4 most commonly used injury models i.e. freeze injury (FI), barium chloride (BaCl2), notexin (NTX) and cardiotoxin (CTX). The FI was the most damaging. In this model, up to 96% of the SCs are destroyed with their surrounding environment (basal lamina and vasculature) leaving a "dead zone" devoid of viable cells. The regeneration process itself is fulfilled in all 4 models with virtually no fibrosis 28 days post-injury, except in the FI model. Inflammatory cells return to basal levels in the CTX, BaCl2 but still significantly high 1-month post-injury in the FI and NTX models. Interestingly the number of SC returned to normal only in the FI, 1-month post-injury, with SCs that are still cycling up to 3-months after the induction of the injury in the other models. CONCLUSIONS: Our studies show that the nature of the injury model should be chosen carefully depending on the experimental design and desired outcome. Although in all models the muscle regenerates completely, the trajectories of the regenerative process vary considerably. Furthermore, we show that histological parameters are not wholly sufficient to declare that regeneration is complete as molecular alterations (e.g. cycling SCs, cytokines) could have a major persistent impact. PMID- 26807983 TI - Impact of soil pH and organic matter on the chemical bioavailability of vanadium species: The underlying basis for risk assessment. AB - The main objective of this study was to unravel the chemical reactions and processes dictating the potential bioavailability of vanadium (V). In environmental solutions V exists in two stable oxidation states, +IV and +V, of which + V is considered to be more toxic. In this study, the effect of speciation and soil pH on the chemical accessibility of V was investigated with two soils: 1) field soil rather rich in soil organic matter (SOM) and 2) coarse mineral soil low in SOM. Fresh soil samples treated with V(+V) (added as NaVO3) or V(+IV) (added as VOSO4) (pH adjusted to the range 4.0-6.9) were incubated for 3 months at 22 degrees C. The adsorption tendency of V species was explored by water extraction (Milli-Q water, 1:50 dw/V) and by sequential extraction (0.25 M KCl; 0.1 M KH2/K2HPO4; 0.1 M NaOH; 0.25 M H2SO4, 1:10 dw/V). The potential bioavailability of V was found to be dictated by soil properties. SOM reduced V(+V) to V(+IV) and acted as a sorbent for both species, which lowered the bioaccessibility of V. A high pH, in turn, favored the predominance of the V(+V) species and thus increased the chemical accessibility of V. PMID- 26807984 TI - Urbanization is a major influence on microplastic ingestion by sunfish in the Brazos River Basin, Central Texas, USA. AB - Microplastics, degraded and weathered polymer-based particles, and manufactured products ranging between 50 and 5000 MUm in size, are found within marine, freshwater, and estuarine environments. While numerous peer-reviewed papers have quantified the ingestion of microplastics by marine vertebrates, relatively few studies have focused on microplastic ingestion by freshwater organisms. This study documents microplastic and manufactured fiber ingestion by bluegill (Lepomis macrochirus) and longear (Lepomis megalotis) sunfish (Centrarchidae) from the Brazos River Basin, between Lake Whitney and Marlin, Texas, USA. Fourteen sample sites were studied and categorized into urban, downstream, and upstream areas. A total of 436 sunfish were collected, and 196 (45%) stomachs contained microplastics. Four percent (4%) of items sampled were debris on the macro size scale (i.e. >5 mm) and consisted of masses of plastic, metal, Styrofoam, or fishing material, while 96% of items sampled were in the form of microplastic threads. Fish length was statistically correlated to the number of microplastics detected (p = 0.019). Fish collected from urban sites displayed the highest mean number of microplastics ingested, followed by downstream and upstream sites. Microplastics were associated with the ingestion of other debris items (e.g. sand and wood) and correlated to the ingestion of fish eggs, earthworms, and mollusks, suggesting that sunfish incidentally ingest microplastics during their normal feeding methods. The high frequency of microplastic ingestion suggest that further research is needed to determine the residence time of microplastics within the stomach and gut, potential for food web transfer, and adverse effects on wildlife and ecosystemic health. PMID- 26807985 TI - Toxicity assessment of perfluorooctane sulfonate using acute and subchronic male C57BL/6J mouse models. AB - Perfluorooctane sulfonate (PFOS) is a principal representative and the final degradation product of several commercially produced perfluorinated compounds. However, PFOS has a high bioaccumulation potential and therefore can exert toxicity on aquatic organisms, animals, and cells. Considering the widespread concern this phenomenon has attracted, we examined the acute and subchronic toxic effects of varying doses of PFOS on adult male C57BL/6 mice. The acute oral LD50 value of PFOS in male C57BL/6J mice was 0.579 g/kg body weight (BW). Exposure to the subchronic oral toxicity of PFOS at 2.5, 5, and 10 mg PFOS/kg BW/day for 30 days disrupted the homeostasis of antioxidative systems, induced hepatocellular apoptosis (as revealed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay), triggered liver injury (as evidenced by the increased serum levels of aspartate aminotransferase, alanine amino transferase, alkaline phosphatase, and gamma-glutamyl transpeptidase and by the altered histology), and ultimately increased the liver size and relative weight of the mice. PFOS treatment caused liver damage but only slightly affected the kidneys and spleen of the mice. This study provided insights into the toxicological effects of PFOS. PMID- 26807986 TI - Physiological and genotype-specific factors associated with grain quality changes in rice exposed to high ozone. AB - Rising tropospheric ozone concentrations in Asia affect the yield and quality of rice. This study investigated ozone-induced changes in rice grain quality in contrasting rice genotypes, and explored the associated physiological processes during the reproductive growth phase. The ozone sensitive variety Nipponbare and a breeding line (L81) containing two tolerance QTLs in Nipponbare background were exposed to 100 ppb ozone (8 h per day) or control conditions throughout their growth. Ozone affected grain chalkiness and protein concentration and composition. The percentage of chalky grains was significantly increased in Nipponbare but not in L81. Physiological measurements suggested that grain chalkiness was associated with a drop in foliar carbohydrate and nitrogen levels during grain filling, which was less pronounced in the tolerant L81. Grain total protein concentration was significantly increased in the ozone treatment, although the albumin fraction (water soluble protein) decreased. The increase in protein was more pronounced in L81, due to increases in the glutelin fraction in this genotype. Amino acids responded differently to the ozone treatment. Three essential amino acids (leucine, methionine and threonine) showed significant increases, while seven showed significant treatment by genotype interactions, mostly due to more positive responses in L81. The trend of increased grain protein was in contrast to foliar nitrogen levels, which were negatively affected by ozone. A negative correlation between grain protein and foliar nitrogen in ozone stress indicated that higher grain protein cannot be explained by a concentration effect in all tissues due to lower biomass production. Rather, ozone exposure affected the nitrogen distribution, as indicated by altered foliar activity of the enzymes involved in nitrogen metabolism, such as glutamine synthetase and glutamine-2-oxoglutarate aminotransferase. Our results demonstrate differential responses of grain quality to ozone due to the presence of tolerance QTL, and partly explain the underlying physiological processes. PMID- 26807987 TI - Distribution of polychlorinated biphenyls, phthalic acid esters, polycyclic aromatic hydrocarbons and organochlorine substances in the Moscow River, Russia. AB - The purpose of this study was to investigate the levels of polychlorinated biphenyl (PCB), phthalic acid esters (PAE), polycyclic aromatic hydrocarbons (PAH) and organochlorine substances (OCP) in the Moscow River water. Some studies have reported the occurrence of these substances in the soil of the Moscow region; however, no study has yet established an overview for these compounds in the Moscow River water. In this study the Moscow River water contamination with PAEs, PAHs and OCPs was determined. Obtained results were associated with the resident area located on the river bank, and the possible contamination sources were considered. The obtained data were compared with the data on the contamination of the different world-wide rivers. This research indicates the further study necessity of the Moscow region to cover more contaminated sites and environmental compartments. PMID- 26807989 TI - D-dimer concentration outliers are not rare in at-term pregnant women. AB - OBJECTIVES: To determine the D-dimer levels in pregnant women at term and the differences between pregnant women with different D-dimer levels. DESIGN AND METHODS: The plasma D-dimer concentrations in pregnant women at term were identified in a cross-sectional study. The clinical indicators that are potentially relevant to D-dimer levels were compared between the pregnant women with different D-dimer levels (i.e., normal, mildly increased, and severely increased). RESULTS: There were always some D-dimer concentration outliers in the pregnant women at term regardless of the presence or absence of complications, and there were no significant differences in maternal age, gestational age, gravidity, parity, blood count, blood coagulation, or liver function between the pregnant women with different D-dimer levels. CONCLUSIONS: D-dimer levels may vary significantly during pregnancy for unknown reasons. This variation, particularly in pregnant women at term, might lead to questionable diagnostic information regarding coagulation. PMID- 26807988 TI - Single amino acid deletion in transmembrane segment D4S6 of sodium channel Scn8a (Nav1.6) in a mouse mutant with a chronic movement disorder. AB - Mutations of the neuronal sodium channel gene SCN8A are associated with lethal movement disorders in the mouse and with human epileptic encephalopathy. We describe a spontaneous mouse mutation, Scn8a(9J), that is associated with a chronic movement disorder with early onset tremor and adult onset dystonia. Scn8a(9J) homozygotes have a shortened lifespan, with only 50% of mutants surviving beyond 6 months of age. The 3 bp in-frame deletion removes 1 of the 3 adjacent isoleucine residues in transmembrane segment DIVS6 of Nav1.6 (p.Ile1750del). The altered helical orientation of the transmembrane segment displaces pore-lining amino acids with important roles in channel activation and inactivation. The predicted impact on channel activity was confirmed by analysis of cerebellar Purkinje neurons from mutant mice, which lack spontaneous and induced repetitive firing. In a heterologous expression system, the activity of the mutant channel was below the threshold for detection. Observations of decreased nerve conduction velocity and impaired behavior in an open field are also consistent with reduced activity of Nav1.6. The Nav1.6Delta1750 protein is only partially glycosylated. The abundance of mutant Nav1.6 is reduced at nodes of Ranvier and is not detectable at the axon initial segment. Despite a severe reduction in channel activity, the lifespan and motor function of Scn8a(9J/9J) mice are significantly better than null mutants lacking channel protein. The clinical phenotype of this severe hypomorphic mutant expands the spectrum of Scn8a disease to include a recessively inherited, chronic and progressive movement disorder. PMID- 26807990 TI - Rett syndrome: An autoimmune disease? AB - Rett syndrome (RTT) is a devastating neurodevelopmental disease, previously included into the autistic spectrum disorders, affecting almost exclusively females (frequency 1:10,000). RTT leads to intellective deficit, purposeful hands use loss and late major motor impairment besides featuring breathing disorders, epilepsy and increased risk of sudden death. The condition is caused in up to 95% of the cases by mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene. Our group has shown a number of previously unrecognized features, such as systemic redox imbalance, chronic inflammatory status, respiratory bronchiolitis associated interstitial lung disease-like lung disease, and erythrocyte morphology changes. While evidence on an intimate involvement of MeCP2 in the immune response is cumulating, we have recently shown a cytokine dysregulation in RTT. Increasing evidence on the relationship between MeCP2 and an immune dysfunction is reported, with, apparently, a link between MECP2 gene polymorphisms and autoimmune diseases, including primary Sjogren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. Antineuronal (i.e., brain proteins) antibodies have been shown in RTT. Recently, high levels of anti-N-glucosylation (N-Glc) IgM serum autoantibodies [i.e., anti CSF114(N-Glc) IgMs] have been detected by our group in a statistically significant number of RTT patients. In the current review, the Authors explore the current evidence, either in favor or against, the presence of an autoimmune component in RTT. PMID- 26807991 TI - Ultrasensitive quantitative LC-MS/MS of an inhibitor of apoptosis protein's antagonist in plasma using protein target affinity extraction. AB - BACKGROUND: A target protein-based affinity extraction LC-MS/MS method was developed to enable plasma level determination following ultralow dosing (0.1-3 ug/kg) of an inhibitor of apoptosis proteins molecule. Methodology & results: Affinity extraction (AE) utilizing immobilized target protein BIR2/BIR3 was used to selectively capture the inhibitor of apoptosis proteins molecule from dog plasma and enable removal of background matrix components. Pretreatment of plasma samples using protein precipitation was found to provide an additional sensitivity gain. A LLOQ of 7.8 pM was achieved by combining protein precipitation with AE. The method was used to support an ultralow dose dog toxicity study. CONCLUSION: AE-LC-MS/MS, utilizing target protein, is a highly sensitive methodology for small molecule quantification with potential for broader applicability. PMID- 26807992 TI - Driven Liouville von Neumann Equation in Lindblad Form. AB - The Driven Liouville von Neumann approach [J. Chem. Theory Comput. 2014, 10, 2927 2941] is a computationally efficient simulation method for modeling electron dynamics in molecular electronics junctions. Previous numerical simulations have shown that the method can reproduce the exact single-particle dynamics while avoiding density matrix positivity violation found in previous implementations. In this study we prove that in the limit of infinite lead models the underlying equation of motion can be cast in Lindblad form. This provides a formal justification for the numerically observed density matrix positivity conservation. PMID- 26807993 TI - Deaths resulting from the use of firearms by police against motor vehicles: Study of cases in Porto, Portugal. AB - The objective of this study was to investigate the terminal ballistics of police shootings in which the bullets went through any motor vehicle structure before fatally wounding the occupants. 6 cases that occurred in Porto district between 1998 and 2013 were studied. The firearms used were 7.65 mm (n = 1) or 9 mm (n = 3) calibre semi-automatic pistols and 9 mm calibre submachine guns (n = 2); the bullets were full metal jacket type. The metal jacket of the collected projectiles was totally or partially destroyed in 3 cases. It exhibited a deformed structure in all cases. The trajectories of the bullets in the vehicles were always more or less linear, even when initial impact was at an oblique angle. The entry holes in the victims' bodies were larger or much larger in size than the calibre of the bullets. They were located, with the exception of one of the cases, in the left half of the body. The trajectories in the victims' bodies were from front to back, in one case, and from back to front in all others. Exit wounds were only found in two cases. Death occurred immediately after the victim was shot only in one case, despite a vital structure has been hit in all cases. The cases studied support the idea that the use of firearms against vehicles with the sole intention of immobilisation entails uncontrollable danger to the lives of the occupants, and especially when done by police forces not specifically trained for that purpose. Therefore, such use of firearms should be avoided. PMID- 26807994 TI - Quantitative analysis of the endogenous GHB level in the hair of the Chinese population using GC/MS/MS. AB - Endogenous production complicates interpretation when gamma-hydroxybutyrate (GHB) is measured in hair for forensic purposes. A method capable of quantifying the endogenous concentration of GHB in human head hair was developed and validated using GC/MS/MS. Hair was digested under alkaline conditions (1 mol/L NaOH, 90 degrees C 10 min), and GHB-d6 was used as an internal standard. Before derivatization with BSTFA and ethyl acetate, a liquid-liquid extraction with ethyl acetate under acidic conditions was performed. GHB-TMS derivatives were detected using GC/MS/MS in the multiple-reaction monitoring mode. This method exhibited good linearity (y = 0.018x + 0.038, R(2) = 0.9998), and the limit of detection was 0.02 ng/mg. The extraction recoveries were more than 60%, and the inter-day and intra-day relative standard deviations (RSD) were less than 15%. This method has been applied for the analysis of the endogenous GHB in hair samples from 66 drug-free Chinese donors. The mean measured concentration for 0-3 cm hair was 1.93 +/- 1.40 ng/mg (n = 66), and extreme values were in the range of 0.28-4.91 ng/mg. The mean male endogenous GHB level was 2.95 ng/mg (0.92-4.91 ng/mg, n = 35), while the mean female level was 0.77 ng/mg (0.28-1.95 ng/mg, n = 31). This method was applied to a forensic case for the determination of GHB in hair samples but it is hard to make a reasonable "cut off" in hair. The solution is to use each subject as his own control. PMID- 26807995 TI - Custody and prison deaths autopsied in Istanbul between 2010 and 2012. AB - The occurred death of a convict in prison, police custody cell or in a hospital always attracts public attention and can be considered as a complex phenomenon. The aim of this study is to evaluate the data obtained from autopsies performed to the custody and prison deaths in Istanbul and to discuss the possible solutions by comparing with the literature. It is also aimed to discuss the postponement of the sentence and presidential amnesty facts in Turkey. Deaths of inmates, which occurred in hospitals, prisons, prison medical rooms, police vans and police custody cells between 2010 and 2012 in Istanbul, Turkey were included in the study. Totally 125 cases were found and 98.4% of them were male. Natural deaths accounted for a great majority of deaths (83.2%). The most common natural cause was cardiovascular diseases. Unnatural deaths accounted for 15.2% of the deaths. Death reason cannot be determined for 1.6% of the cases. More than half of the cases (56%) were died at the hospital, 34.4% were died at the prison, 4% of them at the police van, 3.2% were died under police custody and 2.4% were died at the prison medical room. Moreover, twelve of these cases had applied to Third Specialization Board previously for postponement of the sentence or Presidential amnesty. Totally five of these cases found suitable for postponement of the sentence. Prison conditions should be improved, prisoners with chronic diseases should be examined periodically and if appropriate their sentences should be postponed until they heal. PMID- 26807996 TI - Haematic silicon in drowning. AB - The aim of this paper was to evaluate silicon (Si) concentration in human whole ventricular blood as a further potential chemical marker in the diagnosis of drowning. We employed an acidic digestion for the extraction of soluble Si, and an alkaline digestion for the determination of total Si, including particulate matter, both arising from drowning medium. 29 suspected drowning situations, 24 in fresh water (Fw) and 5 in seawater (Sw), were examined. The difference in Si concentration between the left and right ventricular blood (Si DeltaL-R) was measured and alkaline Si DeltaL-R seems, indeed, a potentially significant complementary tool in the diagnosis of Fw drowning, because insoluble silicon fraction does not undergo hemo-dilution or hemo-concentration, and the DeltaL-R is not affected by exogenous factors. In spite of the limited number of cases investigated, a good correlation was observed between the analytical results and the macro-microscopic autoptic findings. PMID- 26807997 TI - Dental age assessment of Maltese children and adolescents. Development of a reference dataset and comparison with a United Kingdom Caucasian reference dataset. AB - The purpose of this study was to develop and validate a Reference Data Set for Dental Age Assessment of the Maltese population and compare the mean Age of Attainment to a UK Caucasian Reference Data Set. The Maltese Reference Data Set was developed from 1593 Dental Panoramic Tomograms of patients aged between 4 and 26 years, taken from the radiographic archives of the Dental Department, Mater Dei Hospital, Malta. Tooth Development Stages were recorded for all 16 maxillary and mandibular permanent teeth on the left side and both permanent third molars on the right, according to Demirjian's staging method. Summary and percentile data were calculated for each Tooth Development Stage, including the mean Age of Attainment. These means were used to estimate the Dental Age of each subject in the study sample using the simple unweighted average method. The estimated Dental Age was compared to the gold standard of the Chronological Age. Comparison of the Maltese and UK Caucasian Reference Data Set was by a series of t-tests, carried out for each paired Tooth Development Stage by gender. The mean Age of Attainment was slightly higher for the Maltese than the UK Caucasians in both males and females. However there was no statistically significant difference between the Chronological Age and Dental Age for either sex. PMID- 26807998 TI - Dependency of Electrochemical Performances of Silicon Lithium-Ion Batteries on Glycosidic Linkages of Polysaccharide Binders. AB - Molecular structures of polysaccharide binders determining mechanical properties were correlated to electrochemical performances of silicon anodes for lithium-ion batteries. Glycosidic linkages (alpha and beta) and side chains (-COOH and -OH) were selected and proven as the major factors of the molecular structures. Three different single-component polysaccharides were compared: pectin for alpha linkages versus carboxylic methyl cellulose (CMC) for beta-linkages from the linkage's standpoint, and pectin as a COOH-containing polymer and amylose as its non-COOH counterpart from the side chain's standpoint. Pectin was remarkably superior to CMC and amylose in cyclability and rate capability of battery cells based on silicon anodes. The pectin binder allowed volume expansion of silicon electrodes with keeping high porosity during lithiation due to the elastic nature caused by the chair-to-boat conformation in alpha-linkages of its backbone. Physical integrity of pectin-based electrodes was not challenged during repeated lithiation/delithiation cycles without crack development that was observed in rigid CMC-based electrodes. Covalent bonds formed between carboxylic side chains of pectin and silicon surface oxide prevented active silicon mass from being detached away from electric pathways. However, hydrogen bonds between hydroxyl side chains of amylose and silicon surface oxide were not strong enough to keep the silicon mass electrochemically active after cyclability tests. PMID- 26808000 TI - Development of a Pediatric Mass Casualty Triage Algorithm Validation Tool. AB - BACKGROUND: Rapid, accurate evaluation and sorting of victims in a mass casualty incident (MCI) is crucial, as over-triage of victims may overwhelm a trauma system and under-triage may lead to an increase in morbidity and mortality. At this time, there is no validation tool specifically developed for the pediatric population to test an MCI algorithm's inherent capabilities to correctly triage children. OBJECTIVE: To develop a set of criteria for outcomes and interventions to be used as a validation tool for testing an MCI algorithm's ability to correctly triage patients from a cohort of pediatric trauma patients. METHODS: Expert opinion and literature review was used to formulate an initial Criteria Outcomes Tool (COT) that retrospectively categorizes pediatric (<=14 years of age) MCI victims based on resource utilization and clinical outcomes using the classic Red to Black MCI triage designations: Red - cardiopulmonary or mental status compromise needing intervention, Yellow - stable cardiopulmonary status but may require life or limb therapy, Green - minimally injured, and Black - deceased or likely to die given the circumstances. Using an anatomic approach, a list of criteria were defined and a modified-Delphi approach was used to create a summative COT that was reviewed by the American Academy of Pediatrics Disaster Preparedness Advisory Council. The resulting COT was independently applied to a weighted retrospective cohort of 25 pediatric victims from a single Level I trauma center by two reviewers to determine reproducibility. RESULTS: We created a Criteria Outcomes Tool (COT) with 47 outcomes and interventions to validate an MCI algorithm's triage designation. When the COT was applied to a cohort of 25 weighted pediatric charts, we identified the following resource utilization and outcome based triage designations: six Red, six Yellow, six Green, and seven Black triage outcomes. The 100% agreement was obtained between the two reviewers in each of the four categories. CONCLUSIONS: We designed an outcomes and resource utilization tool, the COT, to evaluate the ability of an MCI algorithm to correctly triage pediatric patients. Our tool has good reproducibility on initial study. KEY WORDS: pediatric; disaster; validation tools; triage algorithms; emergency. PMID- 26807999 TI - A Computational Model for the AMPA Receptor Phosphorylation Master Switch Regulating Cerebellar Long-Term Depression. AB - The expression of long-term depression (LTD) in cerebellar Purkinje cells results from the internalisation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) from the postsynaptic membrane. This process is regulated by a complex signalling pathway involving sustained protein kinase C (PKC) activation, inhibition of serine/threonine phosphatase, and an active protein tyrosine phosphatase, PTPMEG. In addition, two AMPAR-interacting proteins glutamate receptor-interacting protein (GRIP) and protein interacting with C kinase 1 (PICK1)-regulate the availability of AMPARs for trafficking between the postsynaptic membrane and the endosome. Here we present a new computational model of these overlapping signalling pathways. The model reveals how PTPMEG cooperates with PKC to drive LTD expression by facilitating the effect of PKC on the dissociation of AMPARs from GRIP and thus their availability for trafficking. Model simulations show that LTD expression is increased by serine/threonine phosphatase inhibition, and negatively regulated by Src-family tyrosine kinase activity, which restricts the dissociation of AMPARs from GRIP under basal conditions. We use the model to expose the dynamic balance between AMPAR internalisation and reinsertion, and the phosphorylation switch responsible for the perturbation of this balance and for the rapid plasticity initiation and regulation. Our model advances the understanding of PF-PC LTD regulation and induction, and provides a validated extensible platform for more detailed studies of this fundamental synaptic process. PMID- 26808001 TI - Functional nanoemulsion-hybrid lipid nanocarriers enhance the bioavailability and anti-cancer activity of lipophilic diferuloylmethane. AB - The purpose of this study was to assess the enhanced physicochemical characteristics, in vitro release behavior, anti-lung cancer activity, gastrointestinal absorption, in vivo bioavailability and bioequivalence of functional nanoemulsion-hybrid lipid nanocarriers containing diferuloylmethane (DNHLNs). The DNHLNs were first fabricated by loading water-in-oil nanoemulsions into hybrid lipid nanosystems using nanoemulsion-thin film-sonication dispersion technologies. The in situ absorption and in vitro and in vivo kinetic features of DNHLNs were measured using an in situ unidirectional perfusion method, a dynamic dialysis method and a plasma concentration-time profile-based method, respectively. The cytotoxic effects of DNHLNs in lung adenocarcinoma A549 cells were examined using MTT colorimetric analysis. The absorptive constants and permeabilities of DNHLNs in four gastrointestinal sections increased by 1.43-3.23 times and by 3.10-7.76 times that of diferuloylmethane (DIF), respectively. The relative bioavailability of DNHLNs to free DIF was 855.02%. DNHLNs inhibited cancer cell growth in a time- and dose-dependent manner. DNHLNs markedly improved the absorption and bioavailability of DIF after oral administration. DNHLNs had stronger inhibitory effects on the viability of A549 cells than that of free DIF. DNHLNs might be potentially promising nanocarriers for DIF delivery via the oral route to address unmet clinical needs. PMID- 26808002 TI - Glycyrrhetinic Acid Mediated Drug Delivery Carriers for Hepatocellular Carcinoma Therapy. AB - Glycyrrhetinic acid (GA), the main hydrolysate of glycyrrhizic acid extracted from the root of licorice, has been used in hepatocellular carcinoma (HCC) therapy. Particularly, GA as a ligand in HCC therapy has been widely explored in different drug delivery systems, including liposomes, micelles, and nanoparticles. There is considerable interest worldwide with respect to the development of GA-modified drug delivery systems due to the extensive presence of GA receptors on the surface of hepatocyte. Up until now, much work has been focused on developing GA-modified drug delivery systems which bear good liver- or hepatocyte-targeted efficiency both in vitro and in vivo. Owing to its contribution in overcoming the limitations of low lipophilicity and poor bioavailability as well as its ability to promote receptor-mediated endocytosis, GA-modified drug delivery systems play an important role in enhancing liver targeting efficacy and thus are focused on the treatment of HCC. Moreover, since GA-modified delivery systems present more favorable pharmacokinetic properties and hepatocyte-targeting effects, they may be a promising formulation for GA in the treatment of HCC. In this review, we will give an overview of GA-modified novel drug delivery systems, paying attention to their efficacy in treating HCC and discussing their mechanism and the treatment effects. PMID- 26808003 TI - Changes in Inflammatory Activity after Glaucoma Filtration Surgery in Children with Chronic Anterior Uveitis. AB - PURPOSE: To evaluate changes in inflammatory activity over time in patients with juvenile idiopathic arthritis (JIA)-associated anterior uveitis after two different types of glaucoma surgery. METHODS: Retrospective analysis of 32 patients with JIA who had trabeculectomy (TE, 21 eyes) or Ahmed glaucoma valve implantation (AGV, 11 eyes). Inflammatory activity and use of anti-inflammatory medication were evaluated 1 year prior to surgery and in the first, third, and fifth years after surgery. RESULTS: In both groups IOP decreased significantly from pre-surgery to 2 years after surgery (TE, 31.1 +/- 6.7 to 12.8 +/- 6.1 mmHg, p<0.0001; AGV, 28.5 +/- 8.5 to 14.9 +/- 6.6 mmHg, p<0.001). In the TE group flare, anterior chamber cells, and uveitis activity decreased significantly after surgery, whereas with AGV there was no sustained reduction of flare. CONCLUSIONS: The degree of inflammation in JIA-associated uveitis is significantly reduced after trabeculectomy. PMID- 26808004 TI - Target-oriented therapy: Emerging drugs for atopic dermatitis. AB - INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a life-time prevalence of 10 - 20% in western countries. Patients suffer from stigmatizing eczematous skin lesions, persisting itch and sleep disorders. Starting usually in early childhood the course of AD is heterogeneous. While most frequently AD disappears before adolescence, about 30% of patients show a chronic persisting course. There is an urgent need for new therapeutic options as until now, specific drugs are missing. AREAS COVERED: Over the last years research has made enormous progress in understanding mechanisms involved in AD pathogenesis. Th2 cells and their key cytokines IL-4 and IL-13 as well as TSLP, CRTH2 and IgE are targets for new compounds currently being tested in clinical trials. This review highlights new drugs for AD at all stages of development as well as current promising scientific approaches. EXPERT OPINION: After decades of silence the market for AD drugs has recently become highly active. Amongst all new compounds, dupilumab--an antibody directed against IL-4 and IL-13 receptors--is the most advanced candidate showing convincing efficacy in several phase III studies. The availability of specific drugs for AD will open up a new era in dermatological therapy. PMID- 26808005 TI - DNA Adduct Formation from Metabolic 5'-Hydroxylation of the Tobacco-Specific Carcinogen N'-Nitrosonornicotine in Human Enzyme Systems and in Rats. AB - N'-Nitrosonornicotine (NNN) is carcinogenic in multiple animal models and has been evaluated as a human carcinogen. NNN can be metabolized by cytochrome P450s through two activation pathways: 2'-hydroxylation and 5'-hydroxylation. While most previous studies have focused on 2'-hydroxylation in target tissues of rats, available evidence suggests that 5'-hydroxylation is a major activation pathway in human enzyme systems, in nonhuman primates, and in target tissues of some other rodent carcinogenicity models. In the study reported here, we investigated DNA damage resulting from NNN 5'-hydroxylation by quantifying the adduct 2-(2-(3 pyridyl)-N-pyrrolidinyl)-2'-deoxyinosine (py-py-dI). In rats treated with NNN in the drinking water (7-500 ppm), py-py-dI was the major DNA adduct resulting from 5'-hydroxylation of NNN in vivo. Levels of py-py-dI in the lung and nasal cavity were the highest, consistent with the tissue distribution of CYP2A3. In rats treated with (S)-NNN or (R)-NNN, the ratios of formation of (R)-py-py-dI to (S) py-py-dI were not the expected mirror image, suggesting that there may be a carrier for one of the unstable intermediates formed upon 5'-hydroxylation of NNN. Rat hepatocytes treated with (S)- or (R)-NNN or (2'S)- or (2'R)-5' acetoxyNNN exhibited a pattern of adduct formation similar to that of live rats. In vitro studies with human liver S9 fraction or human hepatocytes incubated with NNN (2-500 MUM) demonstrated that py-py-dI formation was greater than the formation of pyridyloxobutyl-DNA adducts resulting from 2'-hydroxylation of NNN. (S)-NNN formed more total py-py-dI adducts than (R)-NNN in human liver enzyme systems, which is consistent with the critical role of CYP2A6 in the 5' hydroxylation of NNN in human liver. The results of this study demonstrate that the major DNA adduct resulting from NNN metabolism by human enzymes is py-py-dI and provide potentially important new insights into the metabolic activation of NNN in rodents and humans. PMID- 26808006 TI - Inhibition of bacterial and fungal pathogens by the orphaned drug auranofin. AB - BACKGROUND: We identified auranofin as an antimicrobial compound utilizing a high throughput screen using a Caenorhabditis elegans-Staphylococcus aureus infection model. Results/methodology: Treatment of infected nematodes with auranofin resulted in a prolonged survival rate of 95%, reached with 0.78 MUg/ml. Further investigation of the antimicrobial activity of auranofin found inhibition against S. aureus, Enterococcus faecium and Enterococcus faecalis. Importantly, the fungal pathogens Cryptococcus neoformans was also effectively inhibited with an MIC at 0.5 MUg/ml. Auranofin appears to target the thioredoxin system. CONCLUSION: This work provides extensive additional data on the antibacterial effects of auranofin that includes both reference and clinical isolates and reports a novel inhibition of fungal pathogens by this compound. PMID- 26808008 TI - Heart failure with multiple comorbidities. AB - PURPOSE OF REVIEW: It is well known that patients with heart failure also suffer from a large number of comorbid conditions, which confound their heart failure management and adversely affect the prognosis. The purpose of this review is to evaluate the latest developments of these conditions. RECENT FINDINGS: Chronic lung disease commonly coexists with heart failure. It is more prevalent and worsens prognosis more in patients with preserved (heart failure with preserved ejection fraction) than with reduced ejection fraction (heart failure with reduced ejection fraction). Patients with diabetes have increased risk of incident heart failure, and as a comorbid condition it adversely affects prognosis. The relative impact on mortality and heart failure hospitalization remains controversial. Renal dysfunction is also common in patients with heart failure, with similar prevalence among those with preserved ejection fraction and those with reduced ejection fraction. The prognosis seems mainly related to long term changes in kidney function, rather than to short-term changes in serum creatinine. Anemia and iron deficiency have a similar profile in terms of prevalence and impact on prognosis. Recent data suggest a benefit of intravenous iron infusion in patients who are iron deficient. SUMMARY: As patients with comorbid conditions are frequently excluded from clinical trials, future clinical trials should recruit these patients and include endpoints that will be reflective of these conditions. PMID- 26808007 TI - Year in review: bicuspid aortopathy. AB - PURPOSE OF REVIEW: This article outlines the key research contribution to bicuspid aortic valve (BAV) aortopathy over the past 18 months. RECENT FINDINGS: Investigators have further defined the current gaps in knowledge and the scope of the clinical problem of BAV aortopathy. Support for aggressive resection strategies is waning as evidence mounts to suggest that BAV is not similar to genetic connective tissue disorders with respect to aortic risks. The role of cusp fusion patterns and valve-mediated hemodynamics in disease progression is a major area of discovery. Molecular and cellular mechanisms remain elusive and contradictory. SUMMARY: BAV aortopathy is a major public health problem that remains poorly understood. New insights on valve-mediated hemodynamics using novel imaging modalities may lead to more individualized resection strategies and improved clinical guidelines. PMID- 26808009 TI - Year in review: transcatheter aortic valve replacement. AB - PURPOSE OF REVIEW: Transcatheter aortic valve replacement (TAVR) has been effective in prohibitive/high-risk patients. Expansion toward intermediate or even low-risk patients has been proposed. A review of recent developments will help understand current trends and issues. RECENT FINDINGS: The 5-year results from the PARTNER I trial and 2-year results of the CoreValve US Pivotal Trial, together with national registries, confirmed the long-term efficacy and durability of TAVR. Studies including PARTNER II, ADVANCE, and The German Aortic Valve Registry showed short-to mid-term success in intermediate-risk patients. Comparison of balloon-expandable and self-expanding valves in the CHOICE trial associated specific outcome differences with specific valve types, suggesting a more customized approach in valve selection. Short-term results of newer generation valves have demonstrated excellent safety and efficacy with improved designs. Studies on TAVR-specific complications, such as conduction block and arrhythmia, paravalvular aortic regurgitation, and stroke, have renewed ideas about their prognosis, treatment, and prevention. Conscious sedation percutaneous TAVR has become more popular, with excellent outcomes and improved cost savings. SUMMARY: TAVR has been accepted as an effective treatment even for intermediate risk patients. This article aims to review the most recent results and essential issues. PMID- 26808010 TI - A novel Meloidogyne enterolobii effector MeTCTP promotes parasitism by suppressing programmed cell death in host plants. AB - Meloidogyne enterolobii is one of the most important plant-parasitic nematodes that can overcome the Mi-1 resistance gene and damage many economically important crops. Translationally controlled tumour protein (TCTP) is a multifunctional protein that exists in various eukaryotes and plays an important role in parasitism. In this study, a novel M. enterolobii TCTP effector, named MeTCTP, was identified and functionally characterized. MeTCTP was specifically expressed within the dorsal gland and was up-regulated during M. enterolobii parasitism. Transient expression of MeTCTP in protoplasts from tomato roots showed that MeTCTP was localized in the cytoplasm of the host cells. Transgenic Arabidopsis thaliana plants overexpressing MeTCTP were more susceptible to M. enterolobii infection than wild-type plants in a dose-dependent manner. By contrast, in planta RNA interference (RNAi) targeting MeTCTP suppressed the expression of MeTCTP in infecting nematodes and attenuated their parasitism. Furthermore, MeTCTP could suppress programmed cell death triggered by the pro-apoptotic protein BAX. These results demonstrate that MeTCTP is a novel plant-parasitic nematode effector that promotes parasitism, probably by suppressing programmed cell death in host plants. PMID- 26808011 TI - Can patients' daily behaviour patterns contribute to overuse of opioids? PMID- 26808012 TI - Effect of endocannabinoid degradation on pain: role of FAAH polymorphisms in experimental and postoperative pain in women treated for breast cancer. AB - Fatty acid amide hydrolase (FAAH) metabolizes the endocannabinoid anandamide, which has an important role in nociception. We investigated the role of common FAAH single-nucleotide polymorphisms (SNPs) in experimentally induced and postoperative pain. One thousand women undergoing surgery for breast cancer participated in the study. They were tested for cold (n = 900) and heat pain (n = 1000) sensitivity. After surgery, their pain intensities and analgesic consumption were carefully registered. FAAH genotyping was performed using MassARRAY platform and genome-wide chip (n = 926). Association between 8 FAAH SNPs and 9 pain phenotypes was analyzed using linear regression models. The results showed that carrying 2 copies of a missense variant converting proline at position 129 to threonine (rs324420) resulted in significantly lower cold pain sensitivity and less need for postoperative analgesia. More specifically, rs324420 and another highly correlated SNP, rs1571138, associated significantly with cold pain intensity (corrected P value, 0.0014; recessive model). Patients homozygous for the minor allele (AA genotype) were less sensitive to cold pain (beta = -1.48; 95% CI, -2.14 to -0.8). Two other SNPs (rs3766246 and rs4660928) showed nominal association with cold pain, and SNPs rs4141964, rs3766246, rs324420, and rs1571138 nominal association with oxycodone consumption. In conclusion, FAAH gene variation was shown to associate with cold pain sensitivity with P129T/rs324420 being the most likely causal variant as it is known to reduce the FAAH enzyme activity. The same variant showed nominal association with postoperative oxycodone consumption. Our conclusions are, however, limited by the lack of replication and the results should be replicated in an independent cohort. PMID- 26808013 TI - Chronic widespread pain after motor vehicle collision typically occurs through immediate development and nonrecovery: results of an emergency department-based cohort study. AB - Motor vehicle collision (MVC) can trigger chronic widespread pain (CWP) development in vulnerable individuals. Whether such CWP typically develops through the evolution of pain from regional to widespread or through the early development of widespread pain with nonrecovery is currently unknown. We evaluated the trajectory of CWP development (American College of Rheumatology criteria) among 948 European-American individuals who presented to the emergency department (ED) for care in the early aftermath of MVC. Pain extent was assessed in the ED and 6 weeks, 6 months, and 1 year after MVC on 100%, 91%, 89%, and 91% of participants, respectively. Individuals who reported prior CWP at the time of ED evaluation (n = 53) were excluded. Trajectory modeling identified a 2-group solution as optimal, with the Bayes Factor value (138) indicating strong model selection. Linear solution plots supported a nonrecovery model. Although the number of body regions with pain in the non-CWP group steadily declined, the number of body regions with pain in the CWP trajectory group (192/895, 22%) remained relatively constant over time. These data support the hypothesis that individuals who develop CWP after MVC develop widespread pain in the early aftermath of MVC, which does not remit. PMID- 26808015 TI - The passing of a pioneer in pain research. PMID- 26808014 TI - Contextual modulation of pain in masochists: involvement of the parietal operculum and insula. AB - Pain can be modulated by contextual stimuli, such as emotions, social factors, or specific bodily perceptions. We presented painful laser stimuli together with body-related masochistic visual stimuli to persons with and without preferred masochistic sexual behavior and used neutral, positive, and negative pictures with and without painful stimuli as control. Masochists reported substantially reduced pain intensity and unpleasantness in the masochistic context compared with controls but had unaltered pain perception in the other conditions. Functional magnetic resonance imaging revealed that masochists activated brain areas involved in sensory-discriminative processing rather than affective pain processing when they received painful stimuli on a masochistic background. The masochists compared with the controls displayed attenuated functional connectivity of the parietal operculum with the left and right insulae, the central operculum, and the supramarginal gyrus. Masochists additionally showed negative correlations between the duration of interest in masochistic activities and activation of areas involved in motor activity and affective processing. We propose that the parietal operculum serves as an important relay station that attenuates the affective-motivational aspects of pain in masochists. This novel mechanism of pain modulation might be related to multisensory integration and has important implications for the assessment and treatment of pain. PMID- 26808016 TI - Interpenetrated Three-Dimensional Copper-Iodine Cluster-Based Framework with Enantiopure Porphyrin-like Templates. AB - Presented here is an interpenetrated three-dimensional copper-iodine cluster based framework with dia topology based on two different kinds of Cu4I4 subunits that is templated by an enantiopure porphyrin-like Cu(I)(5-eatz)2 unit and shows excellent photocatalytic activity to degrade methylene blue under visible light. PMID- 26808017 TI - Gelatin-hydroxypropyl methylcellulose water-in-water emulsions as a new bio-based packaging material. AB - Gelatin and hydroxypropyl methylcellulose (HPMC) are two incompatible and immiscible biopolymers which cannot form homogeneous composite films using usual methods. In this study, to prevent phase separation, gelatin-HPMC water-in-water (W/W) emulsion was utilized to from transparent composite films by entrapment the HPMC dispersed droplets in gelatin continuous network. The physicochemical and mechanical properties of emulsion-based films containing different amounts (5 30%) of dispersed phase were determined and compared with those of individual polymer-based films. Incorporating HPMC into W/W emulsion-based films had no significant effect on the tensile strength. The flexibility of composite films decreased at HPMC concentrations below 20%. The depletion layer at the droplets interface reduced the diffusion of water vapor molecules because of its hydrophobic nature, so the water vapor permeability remained constant. Increasing the HPMC content in the emulsion films increased the swelling and decreased the transparency. The entrapment of HPMC in continuous gelatin phase decreased its solubility. Therefore, W/W emulsions are capable of holding two incompatible polymers alongside each other within a homogeneous film network without weakening the physical properties. PMID- 26808018 TI - A critical review of algal biomass: A versatile platform of bio-based polyesters from renewable resources. AB - Algal biomass is an excellent renewable resource for the production of polymers and other products due to their higher growth rate, high photosynthetic efficiency, great potential for carbon dioxide fixation, low percentage of lignin and high amount of carbohydrates. Algae contain unique metabolites which are transformed into monomers suitable for development of novel polyesters. This review article mainly focuses on algal bio-refinery concept for polyester synthesis and on exploitation of algae-based biodegradable polyester blends and composites in tissue engineering and controlled drug delivery system. Algae derived hybrid polyester scaffolds are extensively used for bone, cartilage, cardiac and nerve tissue regeneration due to their biocompatibility and tunable biodegradability. Microcapsules and microspheres of algae-derived polyesters have been used for controlled and continuous release of several pharmaceutical agents and macromolecules to produce humoral and cellular immunity with efficient intracellular delivery. PMID- 26808019 TI - Enhanced thermostability of mesophilic endoglucanase Z with a high catalytic activity at active temperatures. AB - This is the first study for therrmostable mutants of mesophilic endoglucanase EngZ from Clostridium cellulovorans using by site-directed mutagenesis. K94R, S365P and their double mutant K94R/S365P had a wide range of active temperatures (30-60 degrees C). In addition, the optimal temperature of K94R/S365P was increased by 7.5 degrees C. K94R/S365P retained 78.3% relative activity at 70 degrees C, while the wild type retained only 5.8%. Especially, K94R/S365P remained 45.1-fold higher activity than the wild type at 70 degrees C. In addition, K94R/S365P was 3.1-fold higher activity than the wild type at 42.5 degrees C, which is the optimal temperature of the wild type. K94R/S365P showed also stimulated in 2.5-fold lower concentration of CaCl2 and delayed aggregation temperature in the presence of CaCl2 compared to the wild type. In pH stability, K94R/S365P was not influenced, but the optimum pH was transferred from pH 7 to pH 6. In long-term hydrolysis, K94R/S365P reduced the newly released reducing sugar yields after 12h reaction; however, the yields consistently increased until 72h. Finally, the total reducing sugar of K94R/S365P was 5.0-fold higher than the wild type at 50 degrees C, pH6. EngZ (K94R/S365P) can support information to develop thermostability of GH9 endoglucanase with a high catalytic efficiency as the potential industrial bioprocess candidate. PMID- 26808020 TI - IL-17A- and IFNgamma-Producing T Cells in Healthy Skin. PMID- 26808021 TI - Predictive Factors and Risk Mapping for Rift Valley Fever Epidemics in Kenya. AB - BACKGROUND: To-date, Rift Valley fever (RVF) outbreaks have occurred in 38 of the 69 administrative districts in Kenya. Using surveillance records collected between 1951 and 2007, we determined the risk of exposure and outcome of an RVF outbreak, examined the ecological and climatic factors associated with the outbreaks, and used these data to develop an RVF risk map for Kenya. METHODS: Exposure to RVF was evaluated as the proportion of the total outbreak years that each district was involved in prior epizootics, whereas risk of outcome was assessed as severity of observed disease in humans and animals for each district. A probability-impact weighted score (1 to 9) of the combined exposure and outcome risks was used to classify a district as high (score >= 5) or medium (score >=2 - <5) risk, a classification that was subsequently subjected to expert group analysis for final risk level determination at the division levels (total = 391 divisions). Divisions that never reported RVF disease (score < 2) were classified as low risk. Using data from the 2006/07 RVF outbreak, the predictive risk factors for an RVF outbreak were identified. The predictive probabilities from the model were further used to develop an RVF risk map for Kenya. RESULTS: The final output was a RVF risk map that classified 101 of 391 divisions (26%) located in 21 districts as high risk, and 100 of 391 divisions (26%) located in 35 districts as medium risk and 190 divisions (48%) as low risk, including all 97 divisions in Nyanza and Western provinces. The risk of RVF was positively associated with Normalized Difference Vegetation Index (NDVI), low altitude below 1000m and high precipitation in areas with solonertz, luvisols and vertisols soil types (p <0.05). CONCLUSION: RVF risk map serves as an important tool for developing and deploying prevention and control measures against the disease. PMID- 26808023 TI - Nontrauma open abdomens: A prospective observational study. AB - BACKGROUND: Damage-control surgery with open abdomen (OA) is described for trauma, but little exists regarding use in the emergency general surgery. This study aimed to better define the following: demographics, indications for surgery and OA, fascial and surgical site complications, and in-hospital/long-term mortality. We hypothesize that older patients will have increased mortality, patients will have protracted stays, they will require specialized postdischarge care, and the indications for OA will be varied. METHODS: A prospective observational study of emergency general surgery OA patients from June 2013 to June 2014 was performed. Demographics, clinical/operative variables, comorbidities, indications for procedure and OA, wound/fascial complications, and disposition were collected. Patients were stratified into age groups (<= 60, 61 79, and >= 80 years). Six-month and 1-year mortality was determined by query of the Social Security Death Index. RESULTS: A total of 338 laparotomies were performed, of which 96 (28%) were managed with an OA. Median age was 61 years (interquartile range [IQR], 0-68 years), and 51% were male. The median Charlson Comorbidity Index was 2 (IQR, 1.5-5.1), and the median hospital stay was 25 days (IQR, 15-50 days). The most common indications for operation were perforated viscus/free air (20%), mesenteric ischemia (17%), peritonitis (16%), and gastrointestinal hemorrhage (12%). The most common indication for OA was damage control (37%). In the 63 patients with fascial closure, there were 9 (14%) wound infections and 6 (10%) fascial dehiscences. A total of 30% of the patients died in the hospital, and an additional six patients died 6 months after discharge. Patients in the oldest age stratum were more likely to die at 6 months than those in the lower strata. CONCLUSION: Older patients were more likely to die by 6 months, the median hospital stay was 3 weeks, and there were multiple indications for OA management. With a 6-month mortality of 36% and 70% of survivors requiring postdischarge care, this population represents a critically ill population meriting additional study. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III. PMID- 26808024 TI - Penetrating neck trauma in children: An uncommon entity described using the National Trauma Data Bank. AB - BACKGROUND: Penetrating neck trauma is uncommon in children; consequently, data describing epidemiology, injury pattern, and management are sparse. The aim of this study was to use the National Trauma Data Bank (NTDB) to describe pediatric penetrating neck trauma (PPNT). METHODS: The NTDB was queried for children (defined as <15 years old) with PPNT between years 2008 and 2012. Descriptive analysis was used to describe age groups (0-5, 6-10, and 11-14 years) and injury type categorized as aerodigestive, vascular, cervical spine, and nerve. RESULTS: A total of 1,238 patients with penetrating neck trauma were identified among 434,788 children in the NTDB (0.28%). Mean age was 7.9 years, and 70.6% of patients were male. The most common mechanisms of injury were stabbing (44%) and gunshot/firearm (24%). Most patients were treated at a pediatric trauma center (65.8%). Computed tomographic scan was the most frequent (42.2%) diagnostic study performed, followed by laryngoscopy (27.0%) and esophagoscopy (27.4%). Almost a quarter of patients (23.7%) went directly to the operating room from the emergency department (ED). Aerodigestive injuries were most common and occurred more frequently in the youngest age group (p < 0.001). Operative procedures for aerodigestive type injuries were most common (82.7%). There were 69 deaths, yielding a mortality rate of 5.6%. When adjusting for age, admission to a pediatric trauma center, and injury type, only vascular injury (odds ratio, 3.92; 95% confidence interval, 2.19-7.24; p < 0.0001) and ED hypotension (odds ratio, 27.12; 95% confidence interval, 15.11-48.67; p < 0.0001) were found to be independently associated with death. CONCLUSION: PPNT is extremely rare--0.28% reported NTDB incidence. Age seems to influence injury type but does not affect mortality. Computed tomographic scan is the dominant diagnostic study used for selective management. Vascular injury type and hypotension on presentation to the ED were independently associated with mortality. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III. PMID- 26808022 TI - The role of biotransformation and oxidative stress in 3,5-dichloroaniline (3,5 DCA) induced nephrotoxicity in isolated renal cortical cells from male Fischer 344 rats. AB - Among the mono- and dichloroanilines, 3,5-dichloroaniline (3,5-DCA) is the most potent nephrotoxicant in vivo and in vitro. However, the role of renal biotransformation in 3,5-DCA induced nephrotoxicity is unknown. The current study was designed to determine the in vitro nephrotoxic potential of 3,5-DCA in isolated renal cortical cells (IRCC) obtained from male Fischer 344 rats, and the role of renal bioactivation and oxidative stress in 3,5-DCA nephrotoxicity. IRCC (~ 4 million cells/ml) from male rats were exposed to 3,5-DCA (0-1.0mM) for up to 120 min. In IRCC, 3,5-DCA was cytotoxic at 1.0mM by 60 min as evidenced by the increased release of lactate dehydrogenase (LDH), but 120 min was required for 3,5-DCA 0.5mM to increase LDH release. In subsequent studies, IRCC were exposed to a pretreatment (antioxidant or enzyme inhibitor) prior to exposure to 3,5-DCA (1.0mM) for 90 min. Cytotoxicity induced by 3,5-DCA was attenuated by pretreatment with inhibitors of flavin-containing monooxygenase (FMO; methimazole, N-octylamine), cytochrome P450 (CYP; piperonyl butoxide, metyrapone), or peroxidase (indomethacin, mercaptosuccinate) enzymes. Use of more selective CYP inhibitors suggested that the CYP 2C family contributed to 3,5-DCA bioactivation. Antioxidants (glutathione, N-acetyl-l-cysteine, alpha-tocopherol, ascorbate, pyruvate) also attenuated 3,5-DCA nephrotoxicity, but oxidized glutathione levels and the oxidized/reduced glutathione ratios were not increased. These results indicate that 3,5-DCA may be activated via several renal enzyme systems to toxic metabolites, and that free radicals, but not oxidative stress, contribute to 3,5-DCA induced nephrotoxicity in vitro. PMID- 26808025 TI - Defining Zone I of penetrating neck trauma: A surgical controversy in the light of clinical anatomy. PMID- 26808026 TI - Building community resilience to dynamic mass casualty incidents: A multiagency white paper in support of the first care provider. PMID- 26808027 TI - The impact of short prehospital times on trauma center performance benchmarking: An ecologic study. AB - BACKGROUND: Emergency medical service (EMS) prehospital times vary between regions, yet the impact of local prehospital times on trauma center (TC) performance is unknown. To inform external benchmarking efforts, we explored the impact of EMS prehospital times on the risk-adjusted rate of emergency department (ED) death and overall hospital mortality at urban TCs across the United States. METHODS: We used a novel ecologic study design, linking EMS data from the National EMS Information System to TCs participating in the American College of Surgeons' Trauma Quality Improvement Program (TQIP) by destination zip code. This approach provided EMS times for populations of injured patients transported to TQIP centers. We defined the exposure of interest as the 90th percentile total prehospital time (PHT) for each TC. TCs were then stratified by PHT quartile. Analyses were limited to adult patients with severe blunt or penetrating trauma, transported directly by land to urban TQIP centers. Random-intercept multilevel modeling was used to evaluate the risk-adjusted relationship between PHT quartile and the outcomes of ED death and overall hospital mortality. RESULTS: During the study period, 119,740 patients met inclusion criteria at 113 TCs. ED death occurred in 1% of patients, and overall mortality was 7.2%. Across all centers, the median PHT was 61 minutes (interquartile range, 53-71 minutes). After risk adjustment, TCs in regions with the shortest quartile of PHTs (<53 minutes) had significantly greater odds of ED death compared with those with the longest PHTs (odds ratio, 2.00; 95% confidence interval, 1.43-2.78). However, there was no association between PHT and overall TC mortality. CONCLUSION: At urban TCs, local EMS prehospital times are a significant predictor of ED death. However, no relationship exists between prehospital time and overall TC risk-adjusted mortality. Therefore, there is no evidence for the inclusion of EMS prehospital time in external benchmarking analyses. PMID- 26808028 TI - Early propranolol after traumatic brain injury is associated with lower mortality. AB - BACKGROUND: beta-Adrenergic receptor blockers (BBs) administered after trauma blunt the cascade of immune and inflammatory changes associated with injury. BBs are associated with improved outcomes after traumatic brain injury (TBI). Propranolol may be an ideal BB because of its nonselective inhibition and ability to cross the blood-brain barrier. We determined if early administration of propranolol after TBI is associated with lower mortality. METHODS: All adults (age >= 18 years) with moderate-to-severe TBI (head Abbreviated Injury Scale [AIS] score, 3-5) requiring intensive care unit (ICU) admission at a Level I trauma center from January 1, 2013, to May 31, 2015, were prospectively entered into a database. Administration of early propranolol was dosed within 24 hours of admission at 1 mg intravenous every 6 hours. Patients who received early propranolol after TBI (EPAT) were compared with those who did not (non-EPAT). Data including demographics, hospital length of stay (LOS), ICU LOS, and mortality were collected. RESULTS: Over 29 months, 440 patients with moderate-to severe TBI met inclusion criteria. Early propranolol was administered to 25% (109 of 440) of the patients. The EPAT cohort was younger (49.6 years vs. 60.4 years, p < 0.001), had lower Glasgow Coma Scale (GCS) score (11.7 vs. 12.4, p = 0.003), had lower head AIS score (3.6 vs. 3.9, p = 0.001), had higher admission heart rate (95.8 beats/min vs. 88.4 beats/min, p = 0.002), and required more days on the ventilator (5.9 days vs. 2.6 days, p < 0.001). Similarities were noted in sex, Injury Severity Score (ISS), admission systolic blood pressure, hospital LOS, ICU LOS, and mortality rate. Multivariate regression showed that EPAT was independently associated with lower mortality (adjusted odds ratio, 0.25; p = 0.012). CONCLUSION: After adjusting for predictors of mortality, early administration of propranolol after TBI was associated with improved survival. Future studies are needed to identify additional benefits and optimal dosing regimens. LEVEL OF EVIDENCE: Therapeutic study, level IV. PMID- 26808029 TI - Re: Sepsis and trauma resuscitation have significant differences. PMID- 26808030 TI - Aspirin as added prophylaxis for deep vein thrombosis in trauma: A retrospective case-control study. AB - BACKGROUND: Current prophylaxis does not completely prevent deep vein thrombosis (DVT) in trauma patients. Recent data suggest that platelets may be a major contributor to hypercoagulability after trauma, indicating a potential role for antiplatelet medications in prophylaxis for DVT. We sought to determine if preinjury aspirin use was associated with a reduced incidence of lower extremity DVT in trauma patients. METHODS: Using a retrospective case-control design, we matched 110 cases of posttrauma lower extremity DVT one-to-one with controls using seven covariates: age, admission date, probability of death, number of DVT risk factors, sex, mechanism of injury, and presence of head injury. Data collected included 26 risk factors for DVT, prehospital medications, and in hospital prophylaxis. Logistic regression models were created to examine the relationship between prehospital aspirin use and posttrauma DVT. RESULTS: Preinjury aspirin was used by 7.3% of cases (patients diagnosed with in-hospital DVT) compared with 13.6% of controls (p = 0.1). Aspirin was associated with a significant protective effect in multivariate analysis, with an odds ratio of 0.17 (95% confidence interval, 0.04-0.68; p = 0.012) in the most complete model. When stratified by other antithrombotic use, aspirin showed a significant effect only when used in combination with heparinoid prophylaxis (odds ratio, 0.35; 95% confidence interval, 0.13-0.93; p = 0.036). CONCLUSION: Preinjury aspirin use seems to significantly lower DVT rate following injury. This association is strongest when heparinoid prophylaxis is prescribed after patients on preinjury aspirin therapy are admitted. Aspirin as added prophylaxis for DVT in trauma patients needs to be further evaluated. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III. PMID- 26808031 TI - Sepsis and trauma resuscitation have significant differences. PMID- 26808032 TI - Computed tomography in hemodynamically unstable severely injured blunt and penetrating trauma patients. AB - BACKGROUND: Dynamic and efficient resuscitation strategies are now being implemented in severely injured hemodynamically unstable (HU) patients as blood products become readily and more immediately available in the trauma room. Our ability to maintain aggressive resuscitation schemes in HU patients allows us to complete diagnostic imaging studies before rushing patients to the operating room (OR). As the criteria for performing computed tomography (CT) scans in HU patients continue to evolve, we decided to compare the outcomes of immediate CT versus direct admission to the OR and/or angio suite in a retrospective study at a government-designated regional Level I trauma center in Cali, Colombia. METHODS: During a 2-year period (2012-2013), blunt and penetrating trauma patients (>= 15 years) with an Injury Severity Score (ISS) greater than 15 who met criteria of hemodynamic instability (systolic blood pressure [SBP] <100 mm Hg and/or heart rate >100 beats/min and/or >= 4 U of packed red blood cells transfused in the trauma bay) were included. Isolated head trauma and patients who experienced a prehospital cardiac arrest were excluded. The main study outcome was mortality. RESULTS: We reviewed 171 patients. CT scans were performed in 80 HU patients (47%) immediately upon arrival (CT group); the remaining 91 patients (53%) went directly to the OR (63 laparotomies, 20 thoracotomies) and/or 8 (9%) to the angio suite (OA group). Of the CT group, 43 (54%) were managed nonoperatively, 37 (46%) underwent surgery (15 laparotomies, 3 thoracotomies), and 2 (5%) underwent angiography (CT OA subgroup). None of the mortalities in the CT group occurred in the CT suite or during their intrahospital transfers. CONCLUSION: There was no difference in mortality between the CT and OA groups in HU patients. CT scan was attainable in 47% of HU patients and avoided surgery in 54% of the cases. Furthermore, CT scan was helpful in deciding definitive/specific surgical management in 46% scanned HU patients who necessitated surgery after CT. LEVEL OF EVIDENCE: Therapy/care management study, level IV. PMID- 26808033 TI - Helicopters and injured kids: Improved survival with scene air medical transport in the pediatric trauma population. AB - BACKGROUND: Helicopter emergency medical services (HEMS) are frequently used to transport injured children, despite unclear evidence of benefit. The study objective was to evaluate the association of HEMS compared with ground emergency medical services (GEMS) transport with outcomes in a national sample of pediatric trauma patients. METHODS: Patients 15 years or younger undergoing scene transport by HEMS or GEMS in the National Trauma Data Bank from 2007 to 2012 were included. Propensity score matching was used to match HEMS and GEMS patients for likelihood of HEMS transport based on demographics, prehospital physiology and time, injury severity, and geographic region. Absolute standardized differences of less than 0.1 indicated adequate covariate balance between groups after matching. The primary outcome was in-hospital survival, while the secondary outcome was discharge disposition in survivors. Conditional logistic regression determined the association between HEMS versus GEMS transport with outcomes while controlling for demographics, admission physiology, injury severity, nonaccidental trauma, and in-hospital complications not accounted for in the propensity score. Subgroup analysis was performed in patients with a transport time of greater than 15 minutes to capture patients with the potential for HEMS transport. RESULTS: A total of 25,700 HEMS/GEMS pairs were matched from 166,594 patients. Groups were well matched, with all propensity score variables having absolute standardized differences of less than 0.1. In matched patients, HEMS was associated with a 72% increase in odds of survival compared with GEMS (adjusted odds ratio, 1.72; 95% confidence interval, 1.26-2.36; p < 0.01). Transport mode was not associated with discharge disposition (p = 0.47). Subgroup analysis included 17,657 HEMS/GEMS pairs. HEMS was again associated with a significant increase in odds of survival (adjusted odds ratio, 1.81; 95% confidence interval, 1.24-2.65; p < 0.01), while transport mode was not associated with discharge disposition (p = 0.58). CONCLUSION: Scene transport by HEMS was associated with improved odds of survival compared with GEMS in pediatric trauma patients. Further study is warranted to understand the underlying mechanisms and develop specific triage criteria for HEMS transport in this population. LEVEL OF EVIDENCE: Therapeutic study, level III. PMID- 26808035 TI - Surgery or stenting for colonic obstruction: A practice management guideline from the Eastern Association for the Surgery of Trauma. AB - BACKGROUND: Colonic obstruction is a surgical emergency, and delay in decompression results in added morbidity and mortality. Advances have led to less invasive procedures such as stenting as a bridge for definitive surgery. The aim of this article was to perform a systematic review regarding colon obstruction (malignant or benign) and to provide recommendations following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. METHODS: A systematic literature review was conducted using the PubMed, EMBASE, and the Cochrane Library databases of published studies. The search was last performed on January 2, 2015. Two independent reviewers extracted the desired variables from the studies. For our meta-analysis, we used Review Manager X.6 (RevMan). Recommendations are provided using GRADE methodology. A single POPULATION, Intervention, Comparator, Outcome (PICO) question with two outcomes was addressed as follows: POPULATION: in adult patients with a colonic obstruction (malignant or benign). INTERVENTION: should surgery be performed.Comparator: versus endoscopic stenting. OUTCOMES: decreased mortality and decreased emergency, nonplanned procedures? RESULTS: The search yielded 210 results. Screening of the titles excluded 102 articles, leaving 108 for review. After abstract review, 71 additional articles were excluded because of failure to address the PICO questions of this guideline. Thirty-seven articles were reviewed in their entirety, of those six randomized control trials that evaluated the use of stents versus emergency surgery in colonic obstruction caused by malignant disease were included in the final qualitative review. CONCLUSION: We conditionally recommend endoscopic, colonic stenting (if available) as initial therapy for colonic obstruction. In our review, stent use was associated with decreased mortality and rates for emergency, nonplanned procedures to include reoperations. This conditional recommendation is limited to those with malignancy because of the lack of literature supporting this practice in benign colonic disease. PMID- 26808036 TI - Alone we can do so little, together we can do so much. PMID- 26808037 TI - Purpose. PMID- 26808038 TI - Control of severe intra-abdominal hemorrhage with an infusible platelet-derived hemostatic agent in a nonhuman primate (rhesus macaque) model. AB - BACKGROUND: Hemorrhage remains the leading cause of potentially survivable trauma mortality. Recent reports indicate that injuries sustained in noncompressible anatomic locations (i.e., truncal and junctional) account for 86.5% of hemorrhage related deaths. Infusible human platelet-derived hemostatic agents (hPDHAs) represent a promising strategy to reduce blood loss from noncompressible injuries. Here, we evaluate the hemostatic efficacy of a lyophilized hPDHA in a rhesus macaque model of severe, uncontrolled hemorrhage. METHODS: Hemorrhage was induced via laparoscopic 60% left-lobe hepatectomy in anesthetized rhesus macaques (T = 0 minute). Treatment infusion began with an 11-mL bolus (T = 5-6 minutes) of either 5% albumin solution (control; n = 8) or hPDHA (1.2 * 10(10) platelet equivalents, n = 8), followed by 2.8-mL/min 0.9% normal saline at T = 6 20 minutes. Resuscitation continued with normal saline (0.22 mL/kg/min) to a total volume of 20 mL/kg at T = 120 minutes, at which time surgical hemostasis was achieved and percent blood loss quantified. Animals were monitored until T = 480 minutes and then euthanized, and necropsy was performed with emphasis on intravascular and end-organ thrombi. Data are expressed as mean +/- SEM; significance, p < 0.05. RESULTS: Both groups exhibited a ~70% decrease in mean arterial pressure (MAP) from T = 0-5 minutes. Percent blood loss was 44.2 +/- 3.9% in hPDHA animals, and 44.3 +/- 3.3% in controls. Survival rates were 4 of 8 for hPDHA animals and 7 of 8 for controls. Regardless of treatment, percent blood loss was greater (p < 0.02) in nonsurviving animals (55 +/- 2%, n = 5) compared with surviving animals (42% +/- 3%, n = 11). No pathologic intravascular thrombi were observed in either group. CONCLUSION: The isolated administration of hPDHA did not significantly reduce blood loss; however, thrombocytopenia was not present in the model, and clinically, platelets would be administered in combination with plasma. Mortality was not statistically different between groups (p = 0.14) but was related to blood loss. Future studies should consider the use of hPDHA in combination with additional therapeutics (e.g., factors) and a model that incorporates thrombocytopenia or platelet dysfunction. PMID- 26808034 TI - Damage-control resuscitation and emergency laparotomy: Findings from the PROPPR study. AB - BACKGROUND: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial has demonstrated that damage-control resuscitation, a massive transfusion strategy targeting a balanced delivery of plasma-platelet-red blood cell in a ratio of 1:1:1, results in improved survival at 3 hours and a reduction in deaths caused by exsanguination in the first 24 hours compared with a 1:1:2 ratio. In light of these findings, we hypothesized that patients receiving 1:1:1 ratio would have improved survival after emergency laparotomy. METHODS: Severely injured patients predicted to receive a massive transfusion admitted to 12 Level I North American trauma centers were randomized to 1:1:1 versus 1:1:2 as described in the PROPPR trial. From these patients, the subset that underwent an emergency laparotomy, defined previously in the literature as laparotomy within 90 minutes of arrival, were identified. We compared rates and timing of emergency laparotomy as well as postsurgical survival at 24 hours and 30 days. RESULTS: Of the 680 enrolled patients, 613 underwent a surgical procedure, 397 underwent a laparotomy, and 346 underwent an emergency laparotomy. The percentages of patients undergoing emergency laparotomy were 51.5% (174 of 338) and 50.3% (172 of 342) for 1:1:1 and 1:1:2, respectively (p = 0.20). Median time to laparotomy was 28 minutes in both treatment groups. Among patients undergoing an emergency laparotomy, the proportions of patients surviving to 24 hours and 30 days were similar between treatment arms; 24-hour survival was 86.8% (151 of 174) for 1:1:1 and 83.1% (143 of 172) for 1:1:2 (p = 0.29), and 30-day survival was 79.3% (138 of 174) for 1:1:1 and 75.0% (129 of 172) for 1:1:2 (p = 0.30). CONCLUSION: We found no evidence that resuscitation strategy affects whether a patient requires an emergency laparotomy, time to laparotomy, or subsequent survival. LEVEL OF EVIDENCE: Therapeutic study, level IV. PMID- 26808039 TI - Resuscitative endovascular balloon occlusion of the aorta might be dangerous in patients with severe torso trauma: A propensity score analysis. AB - BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a key procedure in early trauma care that provides hemorrhage control in hemodynamically unstable torso trauma patients. However, the clinical efficacy of REBOA remains uncertain. The objective of this study was to estimate the efficacy of REBOA in surgically treated severe torso trauma patients. METHODS: We obtained data from the nationwide trauma registry in Japan (the Japan Trauma Data Bank) for trauma subjects who had undergone emergency surgery or transcatheter embolization against torso trauma. A logistic regression analysis estimated a propensity score to predict REBOA use from available predictors of in-hospital mortality. We then used a propensity score matching analysis to compare in hospital mortality and door-to-primary surgery time in subjects who underwent REBOA and those who did not. In addition, we used an instrumental variable method to adjust for unmeasured confounding variables as a sensitivity analysis. RESULTS: Overall, 12,053 of the 183,457 trauma patients registered in the Japan Trauma Data Bank were eligible based on selection criteria. Propensity score matching selected 625 patients each for the with-REBOA and without-REBOA groups. The in-hospital mortality was significantly higher in subjects who underwent REBOA (61.8% vs. 45.3%; absolute difference, +16.5%; 95% confident interval, +10.9% to +22.0%). Door-to-primary surgery time was shorter in subjects who underwent REBOA than in those who did not (97 minutes vs. 110 minutes; absolute difference, -14 minutes; 95% confidence interval, -25 minutes to -3 minutes). The sensitivity analysis with the instrumental variable method did not alter the results and estimated nonsignificantly higher in-hospital mortality in REBOA subjects (+16.4%; 95% confidence interval, -0.6% to 33.3%). CONCLUSION: This study showed an association between the use of REBOA and excess mortality in patients with hemodynamically unstable torso trauma that had a median door-to primary surgery time of 97 minutes. Further observational studies with detailed REBOA data are necessary to assess whether selected trauma subgroups could benefit from REBOA. LEVEL OF EVIDENCE: Therapeutic study, level III. PMID- 26808040 TI - Modulating the endotheliopathy of trauma: Factor concentrate versus fresh frozen plasma. AB - BACKGROUND: Transfusion of balanced ratios of plasma to platelets and red blood cells has been shown to reduce early death from exsanguination in trauma patients. Aside from hemostasis, recent work has shown that plasma reduces vascular endothelial permeability, inflammation, and organ edema after hemorrhagic shock (HS), all components of the endotheliopathy of trauma. We hypothesized that Kcentra could have protective effects on the endotheliopathy of trauma comparable with fresh frozen plasma (FFP). METHODS: In vitro, endothelial cell (EC) barrier function was assessed by measuring changes in transendothelial electrical resistance for Kcentra, FFP, and albumin. In vivo, a modified Miles assay was used on mice to study the effects of Kcentra, FFP, and albumin on vascular permeability induced by VEGF-A. The same groups were studied in a second in vivo model of pulmonary vascular leak induced by HS and laparotomy. The identification of proteins in Kcentra was assessed by liquid chromatography/mass spectrometry. RESULTS: We found that FFP and Kcentra inhibit EC permeability. We also found that Kcentra and FFP have equivalent capacity to restore EC adherens junction breakdown induced by VEGF-A. In vivo, we found that Kcentra and FFP, but not albumin, significantly inhibited vascular permeability induced by VEGF-A and HS-induced vascular permeability in mice. Investigation of the protein content of Kcentra by mass spectroscopy revealed that there are a number of proteins in Kcentra, derived from plasma that may have contributory roles in the noted effects of Kcentra on vascular leak. CONCLUSION: Taken together, we have demonstrated that FFP and Kcentra inhibit vascular permeability in vivo and in vitro. These beneficial effects of Kcentra may be due in part to the modulation of vascular function by soluble factors present in Kcentra aside from the known clotting factors II, VII, IX, and X. The clinical implications of these findings are unknown and warrant further investigation. PMID- 26808041 TI - Rapid assessment of shock in a nonhuman primate model of uncontrolled hemorrhage: Association of traditional and nontraditional vital signs to mortality risk. AB - BACKGROUND: Heart rate (HR), systolic blood pressure (SBP) and mean arterial pressure (MAP) are traditionally used to guide patient triage and resuscitation; however, they correlate poorly to shock severity. Therefore, improved acute diagnostic capabilities are needed. Here, we correlated acute alterations in tissue oxygen saturation (StO2) and end-tidal carbon dioxide (ETCO2) to mortality in a rhesus macaque model of uncontrolled hemorrhage. METHODS: Uncontrolled hemorrhage was induced in anesthetized rhesus macaques by a laparoscopic 60% left lobe hepatectomy (T = 0 minute). StO2, ETCO2, HR, as well as invasive SBP and MAP were continuously monitored through T = 480 minutes. At T = 120 minutes, bleeding was surgically controlled, and blood loss was quantified. Data analyses compared nonsurvivors (expired before T = 480 minutes, n = 5) with survivors (survived to T = 480 minutes, n = 11) using repeated-measures analysis of variance with Bonferroni correction. All p < 0.05 was considered statistically significant. Results were reported as mean +/- SEM. RESULTS: Baseline values were equivalent between groups for each parameter. In nonsurvivors versus survivors at T = 5 minutes, StO2 (55% +/- 10% vs. 78% +/- 3%, p = 0.02) and ETCO2 (15 +/- 2 vs. 25 +/- 2 mm Hg, p = 0.0005) were lower, while MAP (18 +/- 1 vs. 23 +/- 2 mm Hg, p = 0.2), SBP (26 +/- 2 vs. 34 +/- 3 mm Hg, p = 0.4), and HR (104 +/- 13 vs. 105 +/- 6 beats/min, p = 0.3) were similar. Association of values over T = 5-30 minutes to mortality demonstrated StO2 and ETCO2 equivalency with a significant group effect (p <= 0.009 for each parameter; R(2) = 0.92 and R(2) = 0.90, respectively). MAP and SBP associated with mortality later into the shock period (p < 0.04 for each parameter; R(2) = 0.91 and R(2) = 0.89, respectively), while HR yielded the lowest association (p = 0.8, R(2) = 0.83). CONCLUSION: Acute alterations in StO2 and ETCO2 strongly associated with mortality and preceded those of traditional vital signs. The continuous, noninvasive aspects of Food and Drug Administration-approved StO2 and ETCO2 monitoring devices provide logistical benefits over other methodologies and thus warrant further investigation. PMID- 26808042 TI - A severe traumatic juxtahepatic blunt venous injury. PMID- 26808044 TI - Transphyseal Fracture of the Distal Humerus. AB - Transphyseal fractures of the distal humerus typically occur in children younger than 3 years secondary to birth trauma, nonaccidental trauma, or a fall from a small height. Prompt and accurate diagnosis of the injury is crucial for a successful outcome. Recognizing that the forearm is not aligned with the humerus on plain radiography can aid in the diagnosis of the injury. Surgical management is most commonly performed with the aid of an arthrogram. Closed reduction and percutaneous pinning techniques similar to those used for supracondylar humerus fractures are employed. The most common complication is cubitus varus caused by a malunion, osteonecrosis of the medial condyle, or growth arrest. A corrective lateral closing wedge osteotomy can be performed to restore a nearly normal carrying angle. PMID- 26808043 TI - The HIV Care Continuum among Female Sex Workers: A Key Population in Lilongwe, Malawi. AB - OBJECTIVE: The HIV care continuum among female sex workers (FSW), a key population, has not been well characterized, especially within the generalized epidemics of sub-Saharan Africa. This was the first study to characterize the HIV care continuum among FSW in Lilongwe, Malawi. METHODS: From July through September 2014, we used venue-based sampling to enroll 200 adult FSW in Lilongwe, Malawi into a cross-sectional evaluation assessing HIV care continuum outcomes. Seropositive FSW, identified using HIV rapid testing, received rapid CD4 counts in addition to viral loads using dried blood spots. We calculated proportions of HIV-infected FSW who had history of care, were on ART, and had suppressed viral load and we used Poisson regression to estimate the associations of demographic characteristics and transmission risk behaviors with each outcome. RESULTS: HIV seroprevalence was 69% (n = 138). Among all FSW the median age was 24 years (IQR: 22-28). Among the 20% who were newly diagnosed and reported previously testing negative, the median time since last HIV test was 11 months (interquartile range: 3-17). The majority (69%) of HIV-infected FSW had a history of HIV care, 52% reported current ART use, and 45% were virally suppressed. Of the FSW who reported current ART use, 86% were virally suppressed. Transmission risk behaviors were not associated with continuum outcomes. CONCLUSIONS: FSW in Lilongwe were predominately young and have a high HIV prevalence. Only half of HIV-infected FSW reported current ART use, but the majority of those on ART were virally suppressed. To reduce ongoing transmission and improve health outcomes, increased HIV testing, care engagement, and ART coverage is urgently needed among FSW. Universal testing and treatment strategies for all FSW in Malawi must be strongly considered. PMID- 26808045 TI - Associations between Passive Maternal Smoking during Pregnancy and Preterm Birth: Evidence from a Meta-Analysis of Observational Studies. AB - Previous studies investigating the relationship between passive maternal smoking and preterm birth reveal inconsistent results. We conducted the current meta analysis of observational studies to evaluate the relationship between passive maternal smoking and preterm birth. We identified relevant studies by searching PubMed, EMBASE, and ISI Web of Science databases. We used random-effects models to estimate summary odds ratios (SORs) and 95% confidence intervals (CIs) for aforementioned association. For the analysis, we included 24 studies that involved a total of 5607 women who experienced preterm birth. Overall, the SORs of preterm birth for women who were ever exposed to passive smoking versus women who had never been exposed to passive smoking at any place and at home were 1.20 (95%CI = 1.07-1.34,I(2) = 36.1%) and 1.16 (95%CI = 1.04-1.30,I(2) = 4.4%), respectively. When we conducted a stratified analysis according to study design, the risk estimate was slightly weaker in cohort studies (SOR = 1.10, 95%CI = 1.00 1.21,n = 16) than in cross-sectional studies (SOR = 1.47, 95%CI = 1.23-1.74,n = 5). Additionally, the associations between passive maternal smoking and preterm birth were statistically significant for studies conducted in Asia (SOR = 1.26, 95%CI = 1.05-1.52), for studies including more than 100 cases of preterm birth (SOR = 1.22, 95%CI = 1.05-1.41), and for studies adjusted for maternal age (SOR = 1.27,95%CI = 1.09-1.47), socioeconomic status and/or education (SOR = 1.28, 95%CI = 1.10-1.49), body mass index (SOR = 1.33, 95%CI = 1.04-1.71), and parity (SOR = 1.27, 95%CI = 1.13-1.43). Our findings demonstrate that passive maternal smoking is associated with an increased risk of preterm birth. Future prospective cohort studies are warranted to provide more detailed results stratified by passive maternal smoking during different trimesters of pregnancy and by different types and causes of preterm birth. PMID- 26808046 TI - Serum folate, vitamin B-12 and cognitive function in middle and older age: The HAPIEE study. AB - BACKGROUND: Nutrient status of B vitamins, particularly folate and vitamin B-12, may be related to cognitive ageing but epidemiological evidence remains inconclusive. OBJECTIVE: The aim of this study was to estimate the association of serum folate and vitamin B-12 concentrations with cognitive function in middle aged and older adults from three Central and Eastern European populations. METHODS: Men and women aged 45-69 at baseline participating in the Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) study were recruited in Krakow (Poland), Kaunas (Lithuania) and six urban centres in the Czech Republic. Tests of immediate and delayed recall, verbal fluency and letter search were administered at baseline and repeated in 2006-2008. Serum concentrations of biomarkers at baseline were measured in a sub-sample of participants. Associations of vitamin quartiles with baseline (n=4166) and follow-up (n=2739) cognitive domain-specific z-scores were estimated using multiple linear regression. RESULTS: After adjusting for confounders, folate was positively associated with letter search and vitamin B-12 with word recall in cross sectional analyses. In prospective analyses, participants in the highest quartile of folate had higher verbal fluency (p<0.01) and immediate recall (p<0.05) scores compared to those in the bottom quartile. In addition, participants in the highest quartile of vitamin B-12 had significantly higher verbal fluency scores (beta=0.12; 95% CI=0.02, 0.21). CONCLUSIONS: Folate and vitamin B-12 were positively associated with performance in some but not all cognitive domains in older Central and Eastern Europeans. These findings do not lend unequivocal support to potential importance of folate and vitamin B-12 status for cognitive function in older age. Long-term longitudinal studies and randomised trials are required before drawing conclusions on the role of these vitamins in cognitive decline. PMID- 26808047 TI - Self-Reported Cancer Prevalence among Hispanics in the US: Results from the Hispanic Community Health Study/Study of Latinos. AB - Cancer has surpassed heart disease as the leading cause of death among Hispanics in the U.S., yet data on cancer prevalence and risk factors in Hispanics in regard to ancestry remain scarce. This study sought to describe (a) the prevalence of cancer among Hispanics from four major U.S. metropolitan areas, (b) cancer prevalence across Hispanic ancestry, and (c) identify correlates of self reported cancer prevalence. Participants were 16,415 individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), who self-identified as Cuban, Dominican, Mexican, Puerto Rican, Central or South American. All data were collected at a single time point during the HCHS/SOL baseline clinic visit. The overall self-reported prevalence rate of cancer for the population was 4%. The rates varied by Hispanic ancestry group, with individuals of Cuban and Puerto Rican ancestry reporting the highest cancer prevalence. For the entire population, older age (OR = 1.47, p < .001, 95% CI, 1.26-1.71) and having health insurance (OR = 1.93, p < .001, 95% CI, 1.42-2.62) were all significantly associated with greater prevalence, whereas male sex was associated with lower prevalence (OR = 0.56, p < .01, 95% CI, .40-.79). Associations between study covariates and cancer prevalence also varied by Hispanic ancestry. Findings underscore the importance of sociodemographic factors and health insurance in relation to cancer prevalence for Hispanics and highlight variations in cancer prevalence across Hispanic ancestry groups. Characterizing differences in cancer prevalence rates and their correlates is critical to the development and implementation of effective prevention strategies across distinct Hispanic ancestry groups. PMID- 26808048 TI - Gelation of Soy Milk with Hagfish Exudate Creates a Flocculated and Fibrous Emulsion- and Particle Gel. AB - Hagfish slime is an ultra dilute, elastic and cohesive hydrogel that deploys within milliseconds in cold seawater from a glandularly secreted exudate. The slime is made of long keratin-like fibers and mucin-like glycoproteins that span a network which entraps water and acts as a defense mechanism against predators. Unlike other hydrogels, the slime only confines water physically and is very susceptible to mechanical stress, which makes it unsuitable for many processing operations and potential applications. Despite its huge potential, little work has been done to improve and functionalize the properties of this hydrogel. To address this shortcoming, hagfish exudate was mixed with a soy protein isolate suspension (4% w/v) and with a soy emulsion (commercial soy milk) to form a more stable structure and combine the functionalities of a suspension and emulsion with those of the hydrogel. Hagfish exudate interacted strongly with the soy systems, showing a markedly increased viscoelasticity and water retention. Hagfish mucin was found to induce a depletion and bridging mechanism, which caused the emulsion and suspension to flocculate, making "soy slime", a cohesive and cold-set emulsion- and particle gel. The flocculation network increases viscoelasticity and substantially contributes to liquid retention by entrapping liquid in the additional confinements between aggregated particles and protein fibers. Because the mucin-induced flocculation resembles the salt- or acid induced flocculation in tofu curd production, the soy slime was cooked for comparison. The cooked soy slime was similar to conventional cooked tofu, but possessed a long-range cohesiveness from the fibers. The fibrous, cold-set, and curd-like structure of the soy slime represents a novel way for a cold coagulation and fiber incorporation into a suspension or emulsion. This mechanism could be used to efficiently gel functionalized emulsions or produce novel tofu like structured food products. PMID- 26808049 TI - Quantitative Modeling of Microbial Population Responses to Chronic Irradiation Combined with Other Stressors. AB - Microbial population responses to combined effects of chronic irradiation and other stressors (chemical contaminants, other sub-optimal conditions) are important for ecosystem functioning and bioremediation in radionuclide contaminated areas. Quantitative mathematical modeling can improve our understanding of these phenomena. To identify general patterns of microbial responses to multiple stressors in radioactive environments, we analyzed three data sets on: (1) bacteria isolated from soil contaminated by nuclear waste at the Hanford site (USA); (2) fungi isolated from the Chernobyl nuclear-power plant (Ukraine) buildings after the accident; (3) yeast subjected to continuous gamma irradiation in the laboratory, where radiation dose rate and cell removal rate were independently varied. We applied generalized linear mixed-effects models to describe the first two data sets, whereas the third data set was amenable to mechanistic modeling using differential equations. Machine learning and information-theoretic approaches were used to select the best-supported formalism(s) among biologically-plausible alternatives. Our analysis suggests the following: (1) Both radionuclides and co-occurring chemical contaminants (e.g. NO2) are important for explaining microbial responses to radioactive contamination. (2) Radionuclides may produce non-monotonic dose responses: stimulation of microbial growth at low concentrations vs. inhibition at higher ones. (3) The extinction-defining critical radiation dose rate is dramatically lowered by additional stressors. (4) Reproduction suppression by radiation can be more important for determining the critical dose rate, than radiation-induced cell mortality. In conclusion, the modeling approaches used here on three diverse data sets provide insight into explaining and predicting multi-stressor effects on microbial communities: (1) the most severe effects (e.g. extinction) on microbial populations may occur when unfavorable environmental conditions (e.g. fluctuations of temperature and/or nutrient levels) coincide with radioactive contamination; (2) an organism's radioresistance and bioremediation efficiency in rich laboratory media may be insufficient to carry out radionuclide bioremediation in the field--robustness against multiple stressors is needed. PMID- 26808051 TI - Providing palliative care for cardiovascular disease from a perspective of sociocultural diversity: a global view. AB - PURPOSE OF REVIEW: This article discusses the available information on providing palliative care for cardiovascular disease (CVD) for individuals from culturally and linguistically diverse populations, and argues the need for cultural competence and awareness of healthcare providers. RECENT FINDINGS: The burden of CVD is increasing globally and access to palliative care for individuals and populations is inconsistent and largely driven by policy, funding models, center based expertise and local resources. Culture is an important social determinant of health and moderates health outcomes across the life trajectory. Along with approachability, availability, accommodation, affordability and appropriateness, culture moderates access to services. Health disparities and inequity of access underscore the importance of ensuring services meet the needs of diverse populations and that care is provided by individuals who are culturally competent. In death and dying, the vulnerability of individuals, families and communities is most pronounced. Using a social-ecological model as an organising framework, we consider the evidence from the literature in regard to the interaction between the individual, interpersonal relationships, community and society in promoting access to individuals with cardiovascular disease. SUMMARY: This review highlights the need for considering individual, provider and system factors to tailor and target healthcare services to the needs of culturally diverse populations. Beyond translation of materials, there is a need to understand the cultural dimensions influencing health-seeking behaviors and acceptance of palliative care and ensuring the cultural competence of health professionals in both primary and specialist palliative care. PMID- 26808050 TI - Osmolality of Cerebrospinal Fluid from Patients with Idiopathic Intracranial Hypertension (IIH). AB - INTRODUCTION: Idiopathic intracranial hypertension (IIH) is a disorder of increased intracranial fluid pressure (ICP) of unknown etiology. This study aims to investigate osmolality of cerebrospinal fluid (CSF) from patients with IIH. METHODS: We prospectively collected CSF from individuals referred on suspicion of IIH from 2011-2013. Subjects included as patients fulfilled Friedman and Jacobson's diagnostic criteria for IIH. Individuals in whom intracranial hypertension was refuted were included as controls. Lumbar puncture with ICP measurement was performed at inclusion and repeated for patients after three months of treatment. Osmolality was measured with a Vapor Pressure Osmometer. RESULTS: We collected 90 CSF samples from 38 newly diagnosed patients and 28 controls. At baseline 27 IIH-samples and at 3 months follow-up 35 IIH-samples were collected from patients. We found no significant differences in osmolality between 1) patients at baseline and controls (p = 0. 86), 2) patients at baseline and after 3 months treatment (p = 0.97), and 3) patients with normalized pressure after 3 months and their baseline values (p = 0.79). Osmolality in individuals with normal ICP from 6-25 cmH2O (n = 41) did not differ significantly from patients with moderately elevated ICP from 26-45 cmH2O (n = 21) (p = 0.86) and patients with high ICP from 46-70 cmH2O (n = 4) (p = 0.32), respectively. There was no correlation between osmolality and ICP, BMI, age and body height, respectively. Mean CSF osmolality was 270 mmol/kg (+/- 1 SE, 95% confidence interval 267-272) for both patients and controls. CONCLUSIONS: CSF osmolality was normal in patients with IIH, and there was no relation to treatment, ICP, BMI, age and body height. Mean CSF osmolality was 270 mmol/kg and constitutes a reference for future studies. Changes in CSF osmolality are not responsible for development of IIH. Other underlying pathophysiological mechanisms must be searched. PMID- 26808052 TI - Erectile dysfunction after radical prostatectomy: prevalence, medical treatments, and psychosocial interventions. AB - PURPOSE OF REVIEW: This review will discuss erectile dysfunction in prostate cancer patients following radical prostatectomy . It will focus on the prevalence and current treatments for erectile dysfunction as well as the emotional impact of erectile dysfunction and the current psychosocial interventions designed to help patients cope with this side effect. RECENT FINDINGS: Although there is a large discrepancy in prevalence rates of erectile dysfunction after radical prostatectomy, several recent studies have cited rates as high as 85%. The concept of 'penile rehabilitation' is now the standard of practice to treat erectile dysfunction following radical prostatectomy. However, many men avoid seeking help or utilizing erectile dysfunction treatments. This avoidance is related to the shame, frustration, and distress many men with erectile dysfunction and their partners experience. Recent psychosocial interventions have been developed to facilitate the use of treatments and help men cope with erectile dysfunction. These interventions have shown initial promise, however, continued intervention development is needed to reduce distress and improve long term erectile function outcomes. SUMMARY: Erectile dysfunction is a significant problem following prostate cancer surgery. Although there are effective medical treatments, the development of psychosocial interventions should continue to evolve to maximize the assistance we can give to men and their partners. PMID- 26808053 TI - Perfectionistic Concerns, Social Negativity, and Subjective Well-Being: A Test of the Social Disconnection Model. AB - Partner-specific perfectionistic concerns (PC) include concern over mistakes, self-criticism, and socially prescribed perfectionism as it pertains to one's partner. The social disconnection model proposes that PC influences well-being indirectly through interpersonal problems. Thus, we hypothesized that social negativity (expressed anger, hostility, and rejection) would mediate the relationship between dyadic PC and subjective well-being. Data from 203 romantic dyads (92.1% heterosexual) were collected using self-report surveys and a four wave, 4-week longitudinal design. Participants were predominantly female (53.1%), young (M = 22.69 years), and Caucasian (82.3%). Data were analyzed using an actor partner interdependence model with multilevel structural equation modeling. There were significant actor effects at the between-subjects and within-subjects levels, and significant partner effects for the relationship between PC and social negativity at the within-subject level. Social negativity mediated the relationships between PC and both negative affect and life satisfaction. However, positive affect was more weakly related to PC and social negativity. The social disconnection model was supported. PC was positively associated with one's own social negativity and evoked hostile behaviors from one's partner. Hostile, rejecting behaviors reduced the well-being of the actor, but not the partner. Results suggest perfectionism may be best understood within an interpersonal context. PMID- 26808054 TI - First Report of Rickettsia Identical to R. slovaca in Colony-Originated D. variabilis in the United States: Detection, Laboratory Animal Model, and Vector Competence of Ticks. AB - Ticks of the genus Dermacentor are known vectors of rickettsial pathogens in both the Old World and New World. In North America, Dermacentor variabilis and D. andersoni are vectors of Rickettsia rickettsii, while in Europe, D. marginatus and D. reticulatus transmit R. slovaca and R. raoultii, respectively. Neither the presence of R. slovaca in the Americas nor the ability of American tick species to maintain this pathogen have been reported. Here we describe detection of Rickettsia genetically identical to R. slovaca in D. variabilis, its molecular characterization, assessment of pathogenicity to guinea pigs, and vector competence of D. variabilis ticks. Ticks from a laboratory colony of D. variabilis, established from wild ticks and maintained on naive NZW rabbits, tested positive for spotted fever group (SFG) Rickettsia by PCR. Analysis of 17 kDa gltA, rpoB, ompA, ompB, and sca4 genes revealed 100% identity to R. slovaca sequences available in the GenBank. New Zealand white rabbits fed upon by infected ticks seroconverted to SFG Rickettsia. Guinea pigs inoculated with the Rickettsia culture or infested by the infected ticks developed antibodies to SFG Rickettsia. The intensity of clinical signs and immune response were dependent on dose and route of infection. The identified Rickettsia was detected in all life stages of D. variabilis ticks, confirming transstadial and transovarial transmission. Thirty-six percent of uninfected larvae co-fed with infected nymphs on guinea pigs were PCR-positive and able to pass rickettsia to at least 11.7% of molted nymphs. To our knowledge, this is a first report of identification of a European pathogen R. slovaca or a highly similar agent in the American dog tick, D. variabilis. Considering pathogenicity of R. slovaca in humans, further laboratory and field studies are warranted to assess the relevance of the above findings to the public health and epidemiology of SFG rickettsioses in the United States. PMID- 26808057 TI - Patch-based anisotropic diffusion scheme for fluorescence diffuse optical tomography--part 1: technical principles. AB - Fluorescence diffuse optical tomography (fDOT) provides 3D images of fluorescence distributions in biological tissue, which represent molecular and cellular processes. The image reconstruction problem is highly ill-posed and requires regularisation techniques to stabilise and find meaningful solutions. Quadratic regularisation tends to either oversmooth or generate very noisy reconstructions, depending on the regularisation strength. Edge preserving methods, such as anisotropic diffusion regularisation (AD), can preserve important features in the fluorescence image and smooth out noise. However, AD has limited ability to distinguish an edge from noise. In this two-part paper, we propose a patch-based anisotropic diffusion regularisation (PAD), where regularisation strength is determined by a weighted average according to the similarity between patches around voxels within a search window, instead of a simple local neighbourhood strategy. However, this method has higher computational complexity and, hence, we wavelet compress the patches (PAD-WT) to speed it up, while simultaneously taking advantage of the denoising properties of wavelet thresholding. The proposed method combines the nonlocal means (NLM), AD and wavelet shrinkage methods, which are image processing methods. Therefore, in this first paper, we used a denoising test problem to analyse the performance of the new method. Our results show that the proposed PAD-WT method provides better results than the AD or NLM methods alone. The efficacy of the method for fDOT image reconstruction problem is evaluated in part 2. PMID- 26808055 TI - Selection on protein structure, interaction, and sequence. AB - Characterizing the probabilities of observing amino acid substitutions at specific sites in a protein over evolutionary time is a major goal in the field of molecular evolution. While purely statistical approaches at different levels of complexity exist, approaches rooted in underlying biological processes are necessary to characterize both the context-dependence of sequence changes (epistasis) and to extrapolate to sequences not observed in biological databases. To develop such approaches, an understanding of the different selective forces that act on amino acid substitution is necessary. Here, an overview of selection on and corresponding modeling of folding stability, folding specificity, binding affinity and specificity for ligands, the evolution of new binding sites on protein surfaces, protein dynamics, intrinsic disorder, and protein aggregation as well as the interplay with protein expression level (concentration) and biased mutational processes are presented. PMID- 26808056 TI - Comparative Analysis of Substrate-Free Cultured Oral Mucosal Epithelial Cell Sheets from Cells of Subjects with and without Stevens-Johnson Syndrome for Use in Ocular Surface Reconstruction. AB - PURPOSE: To compare the regenerative potential of cultured oral mucosal epithelial cells sheets (COMECs) from Stevens-Johnson syndrome (SJS) subjects with those from non-SJS subjects. METHODS: Human oral mucosal epithelial cells from SJS and non-SJS subjects were cultured, and colony-forming efficiency (CFE), proliferative and migration potential, expression of cytokines/growth factors and stem cells were compared. COMECs from SJS and non-SJS subjects were transplanted into 12 limbal stem cell-deficient rabbits, and their regenerative potential was analyzed at 1 week after transplantation. RESULTS: CFE (p>0.05, student's t test), cell proliferation potential (p>0.05, two-way ANOVA) and expression of the cytokeratins (K3, K4, K13, K19) in the oral mucosal epithelial cells from SJS subjects were similar to those of the cells from non-SJS subjects. The initial migratory potential of SJS cells was delayed compared to that of non-SJS cells (p <0.05, RM two-way ANOVA). The SJS cells expressed lower levels of EGF and higher levels of VEGF compared to that of non-SJS cells (p<0.05, one-way ANOVA). In vivo transplanted SJS-COMECs showed similar expression of K3, K4, and K13, proliferation markers (Ki-67; p>0.05, Mann-Whitney U test), and stem cell markers (p63; p>0.05, Mann-Whitney U test) compared to non-SJS COMECs. The initial epithelial defects in vivo were larger in the eyes treated with SJS-COMECs on day 3 (p<0.01, RM two-way ANOVA), but no differences were observed by day 7 between SJS- and non-SJS-COMECs. CONCLUSIONS: These results suggest that, aside from differences in migratory potential, oral mucosal epithelial cells from SJS and non-SJS subjects are comparable in their regeneration potential in treating limbal stem cell deficiency. PMID- 26808058 TI - Water-Soluble Luminescent Hybrid Composites Consisting of Oligosilsesquioxanes and Lanthanide Complexes and their Sensing Ability for Cu(2.). AB - Water-soluble hybrid composites with great potential for selective and sensitive sensing and that are obtained through simple, rapid, and environmentally friendly methods are highly desirable and remain a challenging task. Herein, we present luminescent hybrid composites that were realized by linking Na3 [Ln(dpa)3 ] (dpa=2,6-pyridinedicarboxylic acid) to octa-amino functionalized polyhedral oligomeric silsesquioxane (POSS-NH2 ) through hydrogen-bonding interactions between the oxygen atoms of the carboxylate groups of dpa and the hydrogen-bond donor amino groups. The resulting hybrid composites Ln(dpa)3 @POSS-NH2 are highly soluble in aqueous solutions and the quantum yield of Eu(dpa)3 @POSS-NH2 is as high as 56.5 % or 46.3 % in the solid state and in aqueous solution, respectively, as determined by using the integrating sphere method. The novel water-soluble luminescent hybrid composites exhibit high thermal and photostability, and the emitted colors of the resulting hybrid composite can be finely tuned by changing the Eu(3+) /Tb(3+) ratio. Interestingly, Eu(dpa)3 @POSS NH2 hybrid composites exhibited an effective switch-off fluorescence response to Cu(2+) over other common metal ions in aqueous media. PMID- 26808059 TI - Self-Healing Glassy Thin Coating for High-Temperature Applications. AB - Glass thin films (with nanometer to micrometer thicknesses) are promising in numerous applications, both as passive coatings and as active components. Self healing is a feature of many current technological developments as a means of increasing the lifetime of materials. In the context of these developments, we report on the elaboration of the first self-healing glassy thin-film coating developed specifically for high-temperature applications. This coating is obtained by pulsed laser deposition of alternating layers of vanadium boride (VB) and a multicomponent oxide glass. Self-healing is obtained through the oxidation of VB at the operating temperature. The investigation of the effect of elaboration parameters on the coating composition and morphology made it possible to obtain up to seven-layer coatings, with good homogeneity and perfect interfaces, and with a total thickness of less than 1 MUm. The autonomic self healing capacity of the coating has been demonstrated by an in situ experiment, which shows that a crack of nanometric dimension can be healed within a few minutes at 700 degrees C. PMID- 26808060 TI - Development of an Automated and Sensitive Microfluidic Device for Capturing and Characterizing Circulating Tumor Cells (CTCs) from Clinical Blood Samples. AB - Current analysis of circulating tumor cells (CTCs) is hindered by sub-optimal sensitivity and specificity of devices or assays as well as lack of capability of characterization of CTCs with clinical biomarkers. Here, we validate a novel technology to enrich and characterize CTCs from blood samples of patients with metastatic breast, prostate and colorectal cancers using a microfluidic chip which is processed by using an automated staining and scanning system from sample preparation to image processing. The Celsee system allowed for the detection of CTCs with apparent high sensitivity and specificity (94% sensitivity and 100% specificity). Moreover, the system facilitated rapid capture of CTCs from blood samples and also allowed for downstream characterization of the captured cells by immunohistochemistry, DNA and mRNA fluorescence in-situ hybridization (FISH). In a subset of patients with prostate cancer we compared the technology with a FDA approved CTC device, CellSearch and found a higher degree of sensitivity with the Celsee instrument. In conclusion, the integrated Celsee system represents a promising CTC technology for enumeration and molecular characterization. PMID- 26808062 TI - Detection of CEA in human serum using surface-enhanced Raman spectroscopy coupled with antibody-modified Au and gamma-Fe2O3@Au nanoparticles. AB - In this present work, a rapid and simple method to detect carcinoembryonic antigen (CEA) was developed by using surface-enhanced Raman spectroscopy (SERS) coupled with antibody-modified Au and gamma-Fe2O3@Au nanoparticles. First, Au@Raman reporter and gamma-Fe2O3@Au were prepared, and then modified with CEA antibody. When CEA was present, the immuno-Au@Raman reporter and immuno-gamma Fe2O3@Au formed a complex through antibody-antigen-antibody interaction. The selective and sensitive detection of CEA could be achieved by SERS after magnetic separation. Under the optimal conditions, a linear relationship was observed between the Raman peak intensity and the concentration of CEA in the range of 1 50 ng mL(-1) with an excellent correlation coefficient of 0.9942. The limit of detection based on two times ratio of signal to noise was 0.1 ng/mL. The recoveries of CEA standard solution spiked with human serum samples were in the range of 88.5-105.9% with the relative standard deviations less than 17.4%. The method built was applied to the detection of CEA in human serum, and the relative deviations of the analysis results between the present method and electrochemiluminescence immunoassay were all less than 16.6%. The proposed method is practical and has a potential for clinic test of CEA. PMID- 26808061 TI - Confidence as a Common Currency between Vision and Audition. AB - The idea of a common currency underlying our choice behaviour has played an important role in sciences of behaviour, from neurobiology to psychology and economics. However, while it has been mainly investigated in terms of values, with a common scale on which goods would be evaluated and compared, the question of a common scale for subjective probabilities and confidence in particular has received only little empirical investigation so far. The present study extends previous work addressing this question, by showing that confidence can be compared across visual and auditory decisions, with the same precision as for the comparison of two trials within the same task. We discuss the possibility that confidence could serve as a common currency when describing our choices to ourselves and to others. PMID- 26808063 TI - UHPLC/Q-TOFMS-based plasma metabolomics of polycystic ovary syndrome patients with and without insulin resistance. AB - Polycystic ovary syndrome (PCOS), characterized with menstrual irregularities, hyperandrogenism and ovulatory abnormalities, is usually companied with insulin resistance (IR) and accounts for one of the most prevalent reproductive dysfunction of premenopausal women. Despite accumulating investigations, diagnostic standards of this pathological condition remain obscure. The aim of present study is to characterize the plasma metabolic characteristics of PCOS patients with and without IR, and subsequently identify the potential biomarkers for the diagnosis of PCOS and its IR complication. A total of 59 plasma samples from eligible healthy controls (CON, n=19), PCOS patients without IR (non-IR PCOS, n=19) and PCOS patients with IR (IR PCOS, n=21) were profiled by an ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOFMS) followed by multivariate statistical analysis. Compared to the healthy controls, significant decrease in the levels of phosphocholines (PCs) and lyso PC (18:2), and increase in trilauric glyceride level were observed in the plasma of IR PCOS. Meanwhile, the significant increase in the levels of saturated fatty acids (palmitic acid and stearic acid) and decanoylcarnitine, and decrease in PC (36:2) and PS (36:0) were found in non-IR PCOS patients. Trilauric glyceride and decanoylcarnitine were identified as the potential biomarkers with the highest sensitivity and specificity for the diagnosis of PCOS patients with and without IR, respectively. Furthermore, based on these alterations of metabolites, MetPA network pathway analysis suggested a profound involvement of the abnormalities of glycerophospholipid, glycerolipid and fatty acid metabolisms in the pathogenesis of PCOS and IR complications. Collectively, LC-MS-based metabolomics provides a promising strategy for complementary diagnosis of PCOS and its IR complication and offers a new insight to understand their pathogenesis mechanisms. PMID- 26808064 TI - Quality control evaluation of nutraceutical products from Ginkgo biloba using liquid chromatography coupled to high resolution mass spectrometry. AB - Analysis of 11 commercial nutraceutical products obtained from ginkgo has been performed using ultra-high performance liquid chromatography coupled to single stage Orbitrap high resolution mass spectrometry (UHPLC-Orbitrap-MS). The main phytochemicals present in these samples were detected and quantified, utilizing a database containing 65 compounds. Phytochemicals were extracted using a mixture of an aqueous solution of methanol:water (80:20, v/v) in two sequential solid liquid extractions. Adequate validation parameters were obtained. The validated compounds exhibited suitable linearity with determination coefficients (R(2)) higher than 0.99, and intra and inter-day precision were lower than 17 and 22%, respectively. Limits of detection (LODs) and quantification (LOQs) were calculated, ranging from 2 to 10 MUg L(-1), except for myricetin (LOD, 150 MUg L( 1) and LOQ, 300 MUg L(-1)). Results indicate that the amount of terpenoids greatly varies among samples, ranging from 1133 (C7) to 12706 mg kg(-1) (C11). This emphasizes the importance of improve quality control in ginkgo-based products. Moreover, retrospective analysis allowed the detection of some undesirable substances as ginkgolic acid in the samples evaluated. PMID- 26808065 TI - Practical method development for the separation of monoclonal antibodies and antibody-drug-conjugate species in hydrophobic interaction chromatoraphy, part 2: Optimization of the phase system. AB - The goal of this second part was (i) to evaluate the performance of commercially available HIC columns and (ii) to develop a fast and automated "phase system" (i.e. stationary phase and salt type) optimization procedure for the analytical characterization of protein biopharmaceuticals. For this purpose, various therapeutic mAbs (denosumab, palivizumab, pertuzumab, rituximab and bevacizumab) and a cysteine linked ADC (brentuximab-vedotin) were selected as model substances. Several HIC column chemistries (butyl, ether and alkylamide) from different providers were evaluated in four different buffer systems (sodium acetate, sodium chloride, ammonium acetate and ammonium sulfate). As stationary phases, the historical TSK gel Butyl NPR phase and the brand new Thermo MAbPac HIC-10 were found to be the most versatile ones in terms of hydrophobicity, peak capacity and achievable selectivity. As salt types, ammonium sulfate and sodium acetate were found to be particularly well adapted for the analytical characterization of mAbs and ADCs, but it is important to keep in mind that a concentration 2 to 3-times higher of sodium acetate versus ammonium sulfate is required to achieve a similar retention in HIC. After selection of the most appropriate phase systems, the optimization of the separation can be carried out by computer assisted retention modeling in a high throughput manner. PMID- 26808066 TI - Identification of metabolites of selected benzophenanthridine alkaloids and their toxicity evaluation. AB - Selected benzo[c]phenathridine alkaloids were biotransformed using rat liver microsomes and identified by liquid chromatography and mass spectrometry. While the metabolites of commercially available sanguinarine and chelerythrine have been studied in detail, data about the metabolism of the minor alkaloids remained unknown. Reactions involved in transformation include single and/or double O demethylation, demethylenation, reduction, and hydroxylation. Two metabolites, when isolated, purified and tested for toxicity, were found to be less toxic than the original compounds. PMID- 26808067 TI - Detection by LC-MS/MS of HIF stabilizer FG-4592 used as a new doping agent: Investigation on a positive case. AB - Stabilizing the labile factor HIF (hypoxia inducible factor) for therapeutic use has led to the development of various molecules by pharmaceutical companies. These HIF stabilizers show promising erythropoiesis stimulating capacities and are of great interest for patients with chronical kidney disease and anemia. Amongst them FG-4592 from FibroGen is now under phase 3 of clinical studies. While this drug is still under investigation, a parallel market already allows to buy this product, which could be tempting for some athletes willing to increase their performances. To avoid such a use for doping purpose, WADA has listed HIF stabilizers and FG-4592 in particular as prohibited substances since 2011 and some anti-doping laboratories have developed a technique of identification of FG 4592 in urine. Here, we described the first case ever identified by an anti doping laboratory of an athlete using FG-4592. Detection and confirmation in urinary samples was performed by LC-MS/MS. In addition, potential indirect markers erythropoietin (EPO) and hematological parameters followed in the Athlete Biological Passport (ABP) were analyzed during and after the period of use but showed no profound alterations. Only ABPS (abnormal blood profile score) reached (but did not exceed) the upper limit proposed by the ABP adaptive model just after the period of use of FG-4592. Altogether this case sends a warning for anti doping laboratories which now must strengthen surveillance on HIF stabilizers and develop sensitive methods of detection for this new class of drugs. PMID- 26808068 TI - Rapid determination of sildenafil and its analogues in dietary supplements using gas chromatography-triple quadrupole mass spectrometry. AB - Application of gas chromatography-triple quadrupole mass spectrometry for identification, confirmation and quantification of 6 phosphodiesterase-5 (PDE-5) inhibitors (sildenafil, dimethylsildenafil, homosildenafil, thiosildenafil, thiodimethylsildenafil and thiohomosildenafil) in dietary supplements was investigated. The MS was operated in multiple reaction monitoring mode, for better sensitivity and selectivity. In this manner, the method is adequate to reduce background noise with less interference from co-eluting compounds in the samples. Two different ionisation techniques, electron ionisation (EI) and chemical ionisation (CI), were studied and compared. The chromatographic separation was performed on a short 10 m non-polar capillary column without any derivatisation step. This permitted fast analysis for all analogues with retention time less than 11 min, for both techniques. Use of backflushing can aid method retention time reduction and improves column maintenance. Evaluation of method validation included limit of detection (LOD), lower limit of quantitation (LLOQ), linearity, precision and recovery were performed for both EI and CI techniques. The LOD obtained varied from 0.03 to 1.50 MUg/g and the LLOQ ranged from 0.10 to 5.00 MUg/g. Good calibration linearity was obtained for all analogues for both techniques, with correlation coefficients (r(2)) higher than 0.99. Mean recoveries of all analogues using CI show higher values (83.4-108.8%) than that of EI (61.9-91.1%). The intra- and inter-assay precisions were evaluated for all analogues at spiked concentration of 10 MUg/g and the relative standard deviation was less than 15% for both methods. These methods were then successfully applied to dietary supplement samples without prior derivatisation, confirming that the samples were adulterated with sildenafil and/or its analogues. PMID- 26808069 TI - Development of a simple HPLC-UV method for the determination of the hepatitis C virus inhibitor simeprevir in human plasma. AB - A simple high-performance liquid chromatography method for the determination of the hepatitis C virus protease inhibitor simeprevir in human plasma was developed and validated. The method involved a rapid and simple solid-phase extraction of simeprevir using Oasis HLB 1cc cartridges, isocratic reversed-phase liquid chromatography on an XTerra RP18 (150 mm*4.6 mm, 3.5 MUm) column, and ultraviolet detection at 225 nm. The mobile phase consisted of phosphate buffer (pH 6, 52.5 mM) and acetonitrile (30:70, v/v). This assay proved to be sensitive (lower limit of quantification of 0.05 MUg/mL), linear (correlation coefficients >=0.99), specific (no interference with various potentially co-administrated drugs), reproducible (both intra-day and inter-day coefficients of variation <=8.3%), and accurate (deviations ranged from -8.0 to 1.2% and from -3.3 to 6.0% for intra-day and inter-day analysis, respectively). The method was applied to therapeutic monitoring of patients undergoing simeprevir treatment for hepatitis C and proved to be robust and reliable. Thus, this method provides a simple, sensitive, precise and reproducible assay for dosing simeprevir that can be readily adaptable to routine use by clinical laboratories with standard equipment. PMID- 26808071 TI - Three distinct open-pore morphologies from a single particle-filled polymer blend. AB - Ternary mixtures composed of polyisobutylene (PIB), polyethylene oxide (PEO), and silica particles yield three distinct open-pore morphologies depending on the mixture composition: (1) pendular network (particles bonded together by menisci of PEO); (2) capillary aggregate network (particles and PEO form a combined phase with strongly solid-like properties which forms a percolating network); (3) cocontinuous morphology (silica and the PEO form a highly viscous combined phase which retards interfacial tension-driven coarsening). Remarkably, interfacial tension plays altogether different roles in stabilizing these three morphologies: stabilizing the first, not affecting the second, and destabilizing the last. The first two of these morphologies appear to be generalizable to other systems, e.g. to oil/water/particle mixtures. In all three cases, the pores do not collapse even after flow, i.e. all three porous morphologies are amenable to processing. PMID- 26808070 TI - Induction of Viable but Nonculturable State in Rhodococcus and Transcriptome Analysis Using RNA-seq. AB - Viable but nonculturable (VBNC) bacteria, which maintain the viability with loss of culturability, universally exist in contaminated and non-contaminated environments. In this study, two strains, Rhodococcus sp. TG13 and TN3, which were isolated from PCB-contaminated sediment and non-contaminated sediment respectively, were investigated under low temperature and oligotrophic conditions. The results indicated that the two strains TG13 and TN3 could enter into the VBNC state with different incubation times, and could recover culturability by reversal of unfavourable factors and addition of resuscitation promoting factor (Rpf), respectively. Furthermore, the gene expression variations in the VBNC response were clarified by Illumina high throughput RNA-sequencing. Genome-wide transcriptional analysis demonstrated that up-regulated genes in the VBNC cells of the strain TG13 related to protein modification, ATP accumulation and RNA polymerase, while all differentially expressed genes (DEGs) in the VBNC cells of the strain TN3 were down-regulated. However, the down-regulated genes in both the two strains mainly encoded NADH dehydrogenase subunit, catalase, oxidoreductase, which further verified that cold-induced loss of ability to defend oxidative stress may play an important role in induction of the VBNC state. This study further verified that the molecular mechanisms underlying the VBNC state varied with various bacterial species. Study on the VBNC state of non pathogenic bacteria will provide new insights into the limitation of environmental micro-bioremediation and the cultivation of unculturable species. PMID- 26808072 TI - Gelatin-coated Gold Nanoparticles as Carriers of FLT3 Inhibitors for Acute Myeloid Leukemia Treatment. AB - This study presents the design of a gold nanoparticle (AuNPs)-drug system with improved efficiency for the treatment of acute myeloid leukemia. The system is based on four different FLT3 inhibitors, namely midostaurin, sorafenib, lestaurtinib, and quizartinib, which were independently loaded onto gelatin coated gold nanoparticles. Detailed investigation of the physicochemical properties of the formed complexes lead to the selection of quizartinib-loaded AuNPs for the in vitro evaluation of the biological effects of the formed complex against OCI-AML3 acute myeloid leukemia cells. Viability tests by MTT demonstrated that the proposed drug complex has improved efficacy when compared with the drug alone. The obtained results constitute a premise for further in vivo investigation of such drug vehicles based on AuNPs. To the best of our knowledge, this is the first study that investigates the delivery of the above mentioned FLT3 inhibitors via gelatin-coated gold nanoparticles. PMID- 26808073 TI - Ultrathin Icosahedral Pt-Enriched Nanocage with Excellent Oxygen Reduction Reaction Activity. AB - Cost-efficient utilization of Pt in the oxygen reduction reaction (ORR) is of great importance for the potential industrial scale demand of proton-exchange membrane fuel cells. Designing a hollow structure of a Pt catalyst offers a great opportunity to enhance the electrocatalytic performance and maximize the use of precious Pt. Herein we report a routine to synthesize ultrathin icosahedral Pt enriched nanocages. In detail, the Pt atoms were conformally deposited on the surface of Pd icosahedral seeds, followed by selective removal of the Pd core by a concentrated HNO3 solution. The icosahedral Pt-enriched nanocage that is a few atomic layers thick includes the merits of abundant twin defects, an ultrahigh surface/volume ratio, and an ORR-favored Pt{111} facet, all of which have been demonstrated to be promoting factors for ORR. With a 10 times higher specific activity and 7 times higher mass activity, this catalyst shows more extraordinary ORR activity than the commercial Pt/C. The ORR activity of icosahedral Pt enriched nanocages outperforms the cubic and octahedral nanocages reported in the literature, demonstrating the superiority of the icosahedral nanocage structure. PMID- 26808074 TI - Impact of obesity on the clinical outcome of rheumatologic patients in biotherapy. AB - There is raising interest in the scientific community about the impact of body mass on different rheumatologic diseases. A growing body of evidence suggests that the effect of obesity on joint structure goes beyond the simply overload but is based on a complex interwinding of cytokines, hormones, growth factors, and intracellular regulators that at different stages can modify the course of a rheumatologic disease and the clinical response to biotherapies. In these settings, psoriatic arthritis (PsA) and rheumatoid arthritis (RA) have been the more extensively studied. Intriguing is the finding that the interaction between obesity and diseases seems different for PsA or RA. Concerning PsA, epidemiologic studies have provided robust data about the association between obesity and prevalence of psoriasis or PsA. Yet obesity is associated with an increase in degree of disability and poor clinical outcome on treatment with anti-tumor necrosis factor (TNF) drugs. Nevertheless, there are clues suggesting that weight reduction above 5% from baseline increases the probability of achieving a good clinical response in PsA patients on anti-TNF drugs. On the contrary, the epidemiological association between obesity and RA seems to be restricted to some categories of patients with peculiar demographic and autoimmune status. Furthermore, obesity definitely impairs the clinical response of RA patients to anti-TNF treatment, and this might be an effect limited to TNF-blocking agents, as preliminary studies are not confirming these findings for abatacept or tocilizumab. However, the most puzzling aspect of the impact of obesity on RA is that obese patients tend to have a more clinical active disease, an impaired response to biotherapies, and a less radiographically evident joint damage over time. The latter is a very stimulating issue and the knowledge of the underlying mechanisms should be an auspicious challenge for the researchers, which will provide further insights on the overall management of RA. PMID- 26808075 TI - Coexistence of ischemic heart disease and rheumatoid arthritis patients-A case control study. AB - BACKGROUND: Over the last few decades, several studies have demonstrated the connection between Rheumatoid Arthritis (RA) and Ischemic Heart Disease (IHD). The additional risk for RA patients to also suffer from IHD varies based on the definition of the diseases in question, the populations evaluated, and the variables included in the studies. OBJECTIVES: To quantify the association between RA and IHD according to certain demographics as well as traditional cardiovascular risk factors in order to determine their roles in the development of coronary artery disease among patients with RA. METHODS: Using data from the largest HMO in Israel, the Clalit Health Services, we selected for patients with RA. These patients were compared with age and sex matched controls with regards to the prevalence of IHD in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. RESULTS: The study included 11,782 patients with RA and 57,973 age and sex matched controls. The prevalence of IHD in patients with RA was increased compared with the prevalence in controls (16.6% and 12.8% respectively, P<0.001). In a multivariate analysis, RA was associated with higher proportions of IHD (OR 1.346, 95% confidence interval 1.255-1.431). PMID- 26808076 TI - Radiological and clinical results of patients after ACDF with and without preoperative software-assisted cage selection. AB - OBJECTIVE: Comparison of software facilitated preoperatively-selected cages versus standard intraoperatively-selected cages, assessing radiological and clinical outcomes of patients after single level cervical discectomy and fusion (ACDF). METHODS: Cages of study group patients were preoperatively chosen via software-aided dimensioning. Controls obtained cages determined by intraoperative trail implants. Primary endpoints were segmental height (SH), regional angulation (RA) and global cervical angulation (GCA) measured on plain radiographs before, immediately and 12 months after surgery. Neck pain on the visual analogue scale, the neck disability index, and patient satisfaction index recorded at 12 months follow up (FU) were the secondary endpoints. RESULTS: Each group comprised of 20 patients and both depicted similar demographics and operated segmental levels. Mean postoperative SH was significantly increased in both study and control groups, p<0.001* and p=0.006* respectively. Immediate postoperative gain of lordosis was only significant for the study group p<0.001*. At 12 months FU, SH and RA decreased significantly in both groups. GCA and all secondary endpoints were similar for various measured time points. The two groups did not show any significant difference for all investigated parameters. CONCLUSION: The radiographical and clinical outcomes of patients receiving cages preoperatively selected by software-assistance are similar to that of patients obtaining conventionally chosen cages. However the former allows for better regional gain/restoration of lordosis. PMID- 26808077 TI - The benefit of early lumbar drain insertion in reducing the length of CSF leak in traumatic rhinorrhea. AB - OBJECTIVE: In traumatic CSF leaks, the early lumbar drain (LD) placement could significantly shorten the rhinorrhea period. METHODS: Included were patients presenting CSF rhinorrhea subsequent to closed head trauma, admitted within 24h. Patients were randomly allocated into two treatment arms: 30 patients within Group A with CSF diversion via LD and 30 patients in Group B managed conservatively with bed rest and head elevation. Primary outcome was length of CSF rhinorrhea. Secondary outcomes were recurrent CSF leaks and meningitis occurrence. RESULTS: In Group A leak stopped within 10 days, in Group B leak persisted beyond 10 days in 2 patients. In Group A CSF leak time was 4.83+/-1.88 days while in Group B was 7.03+/-2.02 days. The difference is statistically significant: 2.2 days (95% CI 3.05-1.35), p<0.0001. During follow-up recurrent CSF leak developed in 7 patients (23%) in Group A and in 8 patients (27%) in Group B (p=0.63, not significant). Meningitis occurred in 3 patients in Group A (10%) and in 4 cases in Group B (13%) (p=0.61, not significant). CONCLUSIONS: The initial use of LDs in highly selected patients with traumatic CSF rhinorrhea resulted in a significant decrease of leakage. Nevertheless, the benefits should be carefully weighted with drawbacks. PMID- 26808078 TI - TBI prognosis calculator: A mobile application to estimate mortality and morbidity following traumatic brain injury. AB - OBJECTIVE: Traumatic Brain Injury (TBI) is a significant public health problem and a leading cause of worldwide mortality and morbidity. Although effective evidence-based guidelines are available to help with management, the first question clinicians and family face is whether or not it is appropriate to intervene at all. To facilitate prognostic assessment and family counseling, we developed mobile application integrating validated TBI prognostic models. METHODS: The medical literature was reviewed to identify existing and validated prognostic models of mortality and morbidity following TBI. After approbation by the selected original model authors, a mobile application incorporating these models was developed. RESULTS: Of more than 100 published models, we identified the MRC CRASH trial-derived models as the most appropriate TBI prognosis tools for mobile use. These were integrated into an application we called "TBI Prognosis Calculator", which allows quick and interactive estimation of 14-days mortality and 6-months mortality and morbidity using demographic, clinical and radiologic variables. The application was programmed both for iOS-and Android compatible devices and released as free applications in the platforms' respective distribution channels. CONCLUSIONS: Prompt and accurate prognosis estimation in TBI is promising. Mobile applications have the potential to enable easier and quicker point-of-care access to validated models, providing additional information to improve management and family counseling. We anticipate that clinicians will find "TBI Prognosis Calculator" useful as an adjunct in their prognostic assessment and family counseling. PMID- 26808079 TI - Time-Dependent Decay of mRNA and Ribosomal RNA during Platelet Aging and Its Correlation with Translation Activity. AB - Previous investigations have indicated that RNAs are mostly present in the minor population of the youngest platelets, whereas translation in platelets could be biologically important. To attempt to solve this paradox, we studied changes in the RNA content of reticulated platelets, i.e., young cells brightly stained by thiazole orange (TObright), a fluorescent probe for RNAs. We provoked in mice strong thrombocytopenia followed by dramatic thrombocytosis characterized by a short period with a vast majority of reticulated platelets. During thrombocytosis, the TObright platelet count rapidly reached a maximum, after which TOdim platelets accumulated, suggesting that most of the former were converted into the latter within 12 h. Experiments on platelets, freshly isolated or incubated ex vivo at 37 degrees C, indicated that their "RNA content", here corresponding to the amounts of extracted RNA, and the percentage of TObright platelets were positively correlated. The "RNA Content" normalized to the number of platelets could be 20 to 40 fold higher when 80-90% of the cells were reticulated (20-40 fg/platelet), than when only 5-10% of control cells were TObright (less than 1fg/platelet). TObright platelets, incubated ex vivo at 37 degrees C or transfused into mice, became TOdim within 24 h. Ex vivo at 37 degrees C, platelets lost about half of their ribosomal and beta actin RNAs within 6 hours, and more than 98% of them after 24 hours. Accordingly, fluorescence in situ hybridization techniques confirmed the presence of beta actin mRNAs in most reticulated-enriched platelets, but detected them in only a minor subset of control platelets. In vitro, constitutive translation decreased considerably within less than 6 hours, questioning how protein synthesis in platelets, especially in non-reticulated ones, could have a biological function in vivo. Nevertheless, constitutive transient translation in young platelets under pathological conditions characterized by a dramatic increase in circulating reticulated platelets could deserve to be investigated. PMID- 26808080 TI - The endogenous cannabinoid anandamide increases human airway epithelial cell permeability through an arachidonic acid metabolite. AB - Injury to the bronchial epithelium in respiratory diseases such as asthma and COPD results in the loss of barrier function and an elevated sensitivity to environmental insults. An increased release of the endogenous cannabinoid, anandamide in response to inhalation of allergen in asthmatic patients has been reported. The aim of this study was, therefore, to determine the effects of endocannabinoids on bronchial epithelial cell permeability and to investigate the mechanisms involved. Calu-3 human bronchial epithelial cells were cultured at air liquid interface to allow development of tight junctions. Changes in Transepithelial Electrical Resistance (TEER), a reflection of epithelial permeability, were measured at various time points post-treatment, and expression of the tight junction proteins, occludin and ZO-1, were determined using Western immunoblotting. Anandamide produced a significant reduction in TEER, which was unaffected by cannabinoid receptor antagonists, but attenuated by URB597, an inhibitor of fatty acid amide hydrolase, and by a combination of cyclooxygenase (COX) and lipoxygenase (LOX) blockade. The anandamide metabolite, arachidonic acid, showed similar TEER decrease that was also prevented in the presence of COX and LOX inhibitor. Expression of occludin and ZO-1 were also reduced by anandamide. These findings indicate a pro-inflammatory-like effect of anandamide on bronchial epithelial permeability, mediated by cyclooxygenase and lipoxygenase metabolites, and suggest that inhibition of anandamide degradation might provide a novel approach to treat airway inflammation. PMID- 26808081 TI - The untapped potential of tyrosine-based G protein signaling. AB - Tyrosine-based and trimeric G protein-based signaling are the two most widely studied and distinct mechanisms for signal transduction in eukaryotes. How each of them relay signals across the plasma membrane independently of each other has been extensively characterized; however, an understanding of how they work together remained obscure. Recently, a rapidly emerging paradigm has revealed that tyrosine based signals are relayed via G proteins, and that the cross-talk between the two hubs are more robustly and sophisticatedly integrated than was previously imagined. More importantly, by straddling the two signaling hubs that are most frequently targeted for their therapeutic significance, the tyrosine based G-protein signaling pathway has its own growing list of pathophysiologic importance, both as therapeutic target in a variety of disease states, and by paving the way for personalized medicine. The fundamental principles of this emerging paradigm and its pharmacologic potential are discussed. PMID- 26808082 TI - Pharmacological opportunities to control inflammatory diseases through inhibition of the leukocyte recruitment. AB - Leukocyte recruitment to tissues is a highly orchestrated process and is one of the pillars of the inflammatory process. The contribution of leukocytes to tissue damage is very clear, suggesting that targeting leukocyte accumulation in tissue to be relevant for the development of novel therapies to treat chronic inflammatory diseases. Here, we review briefly known mechanisms of leukocyte recruitment and suggest potential targets for the development of novel anti inflammatory therapies. PMID- 26808083 TI - Plumbagin, a naphthaquinone derivative induces apoptosis in BRCA 1/2 defective castrate resistant prostate cancer cells as well as prostate cancer stem-like cells. AB - Eventhough the role of BRCA1/2 in hereditary prostatic cancer is being unleashed at a rapid rate; their optimal clinical management remains undefined. Cancer stem cells are thought to be responsible for cancer chemoresistance and relapse, thus they represent a significant concern for cancer prognosis and therapy. In this study, we have analyzed the effect of Plumbagin (PB) and structurally related naphthaquinones on BRCA1/2 silenced prostate cancer cells and the ability of PB to target stem cells. Our cell proliferation studies showed that both PC-3 and DU145 cells were more sensitive to PB, though all the compounds induced mitochondrial potential loss, DNA fragmentation and morphological changes which are indicative of apoptosis. Both BRCA1/2 siRNA transfected PC-3 and DU145 cells exhibited increased sensitivity to PB. Gene expression profiling post PB treatment in BRCA1/2 silenced cells revealed that PB has a putative role in tumor suppression in BRCA defective cancers. Using flow cytometric analysis we have proved that PB has the putative ability to directly target CSCs. Overall studies suggest that PB's antitumour mechanisms holds promise for novel therapeutic approaches against BRCA mutated cancers as well as CSCs. PMID- 26808084 TI - Melatonin's role in preventing toxin-related and sepsis-mediated hepatic damage: A review. AB - The liver is a central organ in detoxifying molecules and would otherwise cause molecular damage throughout the organism. Numerous toxic agents including aflatoxin, heavy metals, nicotine, carbon tetrachloride, thioacetamide, and toxins derived during septic processes, generate reactive oxygen species followed by molecular damage to lipids, proteins and DNA, which culminates in hepatic cell death. As a result, the identification of protective agents capable of ameliorating the damage at the cellular level is an urgent need. Melatonin is a powerful endogenous antioxidant produced by the pineal gland and a variety of other organs and many studies confirm its benefits against oxidative stress including lipid peroxidation, protein mutilation and molecular degeneration in various organs, including the liver. Recent studies confirm the benefits of melatonin in reducing the cellular damage generated as a result of the metabolism of toxic agents. These protective effects are apparent when melatonin is given as a sole therapy or in conjunction with other potentially protective agents. This review summarizes the published reports that document melatonin's ability to protect hepatocytes from molecular damage due to a wide variety of substances (aflatoxin, heavy metals, nicotine, carbon tetrachloride, chemotherapeutics, and endotoxins involved in the septic process), and explains the potential mechanisms by which melatonin provides these benefits. Melatonin is an endogenously-produced molecule which has a very high safety profile that should find utility as a protective molecule against a host of agents that are known to cause molecular mutilation at the level of the liver. PMID- 26808085 TI - The anti-metastatic effect of 8-MOP on hepatocellular carcinoma is potentiated by the down-regulation of bHLH transcription factor DEC1. AB - Despite progress in diagnostics and treatment of hepatocellular carcinoma (HCC), its prognosis remains poor. 8-Methoxypsoralen (8-MOP), a formerly considered photosensitizing agent, has been reported to induce cell apoptosis in HepG2 cells in a modest way when used alone. In this study, it was demonstrated that 8-MOP inhibited HCC HepG2 cells and SMMC-7721 cells migratory and invasive potentiality, as well as modulated the expression of various EMT-associated genes such as enhancing E-cadherin and reducing N-cadherin, vimentin, alpha-SMA and MMP9 in a concentration-dependent way. Differentiated embryonic chondrocyte expressed gene 1, DEC1 (BHLHE40/Stra13/Sharp2), is a basic helix-loop-helix (bHLH) transcription factor that regulates cell growth, differentiation, apoptosis and tumorigenesis. 8-MOP suppressed the expression of DEC1 in a concentration- and time-dependent manner. Overexpression of DEC1 endorsed the HepG2 cells a higher metastatic phenotype, while totally abolished 8-MOP repressed metastatic capability. In the meanwhile, overexpression of DEC1 promoted EMT process by suppressing expression of epithelial protein and enhancing expression of mesenchymal proteins, while potently antagonized the regulation of EMT-associated genes by 8-MOP. In vivo experiments revealed that the treatment of 8-MOP (5 or 20mg/kg) resulted in a dose-dependent decreases in the lung metastasis of hepatoma H22-transplanted mice without any obvious toxicity to the organs, as well as increased expression of E-cadherin in lung tissues. Consistently, 8-MOP down-regulated the expression of DEC1 in the lungs of tumor-bearing mice, which further confirms that DEC1 was correlated with 8-MOP induced anti-metastatic effect. The present findings establish a function for DEC1 in HCC metastatic progression and suggest its candidacy as a novel target for the anti-metastasis effect of 8-MOP. PMID- 26808086 TI - Thinking Big or Small: Does Mental Abstraction Affect Social Network Organization? AB - Four studies examined how mental abstraction affects how people perceive their relationships with other people, specifically, how these relationships may be categorized in social groups. We expected that individuals induced to think abstractly would report fewer more global social groups, compared to those induced to think concretely, who would report more specific groups. However, induced abstract mindset did not affect how people structured their social groups (Study 2-4), despite evidence that the mindset manipulation changed the level of abstraction in their thoughts (Study 3) and evidence that it changed how people structured groups for a control condition (household objects, Study 4). Together, these studies suggest that while the way people organize their relationships into groups is malleable; cognitive abstraction does not seem to affect how people categorize their relationships into social groups. PMID- 26808087 TI - Understanding Perceptions of Climate Change, Priorities, and Decision-Making among Municipalities in Lima, Peru to Better Inform Adaptation and Mitigation Planning. AB - Climate change poses multiple risks to the population of Lima, the largest city and capital of Peru, located on the Pacific coast in a desert ecosystem. These risks include increased water scarcity, increased heat, and the introduction and emergence of vector-borne and other climate sensitive diseases. To respond to these threats, it is necessary for the government, at every level, to adopt more mitigation and adaptation strategies. Here, focus groups were conducted with representatives from five Lima municipalities to determine priorities, perception of climate change, and decision-making processes for implementing projects within each municipality. These factors can affect the ability and desire of a community to implement climate change adaptation and mitigation strategies. The results show that climate change and other environmental factors are of relatively low priority, whereas public safety and water and sanitation services are of highest concern. Perhaps most importantly, climate change is not well understood among the municipalities. Participants had trouble distinguishing climate change from other environmental issues and did not fully understand its causes and effects. Greater understanding of what climate change is and why it is important is necessary for it to become a priority for the municipalities. Different aspects of increased climate change awareness seem to be connected to having experienced extreme weather events, whether related or not to climate change, and to higher socioeconomic status. PMID- 26808088 TI - Trends in direct-to-consumer advertising of prescription contraceptives. AB - OBJECTIVE: Despite much speculation about the role of direct-to-consumer advertising (DTCA) in increasing demand for prescription contraceptives in the United States, there is little published research on this topic. We sought to quantify the prevalence and magnitude of DTCA for prescription contraceptives over the last decade. STUDY DESIGN: Using cross-sectional data from January 2005 through December 2014, we performed descriptive analyses on trends in DTCA expenditure for prescription contraceptives. We also quantified the amount of DTCA according to contraceptive method category and individual brand. RESULTS: During the study period, pharmaceutical companies spent a total of US$1.57 billion in the United States on DTCA of prescription contraceptives. Annual expenditure for contraceptive DTCA reached a peak value of US$260 million in 2008, with a progressive decline to a nadir of US$69 million by 2013. Of the contraceptive methods, oral contraceptive pills (OCPs) have been the most heavily promoted, with Yaz (drospirenone/ethinyl estradiol) - the most advertised brand - accounting for US$347 million of cumulative DTCA expenditure. However, DTCA spending on OCPs peaked in 2007 and was overtaken in 2012 by the DTCA of long acting reversible contraceptives (LARCs), the contraceptive method now receiving the largest amount of DTCA promotion. CONCLUSIONS: DTCA is a major form of promotion for prescription contraceptives. Recent trends in DTCA expenditure indicate a shift from promotion of the OCPs to the LARCs. DTCA's effect on provider and patient utilization of various contraceptive methods has yet to be determined. IMPLICATIONS: This study provides the first quantitative evaluation of DTCA of prescription contraceptive methods and reveals DTCA's importance as a form of promotion. Recent DTCA trends indicate increased promotion of LARCs, coinciding with greater uptake of LARC methods by patients and prescribers. PMID- 26808089 TI - Theory of materials for solar energy conversion. PMID- 26808090 TI - The responses of pulmonary and systemic circulation and airway to anaphylactic mediators in anesthetized BALB/c mice. AB - AIMS: Anaphylactic shock sometimes accompanies pulmonary vaso- and broncho constriction. We previously reported the hemodynamic features of mouse anaphylaxis (Life Sci. 2014; 116: 98-105). However, the effects of anaphylactic chemical mediators on the hemodynamics of in vivo mice are not well known. Furthermore, it is uncertain whether the mediators exert the same directional actions. Therefore, we determined their effects systematically on total peripheral resistance (TPR), pulmonary vascular resistance (PVR), or airway pressure (AWP) in anesthetized mice. MAIN METHODS: We measured directly pulmonary arterial pressure, left atrial pressure, systemic arterial pressure, central venous pressure and aortic blood flow to determine PVR and TPR, as well as AWP, following injections of platelet-activating factor (PAF), histamine, serotonin, leukotriene (LT) C4, and prostaglandin (PG) D2 in anesthetized open-chest artificially ventilated BALB/c mice. KEY FINDINGS: Consecutive administration of any agents increased PVR dose-dependently with the maximal responsiveness being PAF>LTC4>serotonin>>histamine=PGD2. Histamine caused a biphasic PVR response, an initial decrease, which was abolished by L-NAME, followed by an increase at high doses. PAF, serotonin, and histamine decreased TPR dose-dependently, while LTC4 or PGD2 yielded an increase or no change in TPR, respectively. Serotonin, but not the other agents, increased AWP. SIGNIFICANCE: Anaphylactic mediators exert non uniform actions on the pulmonary and systemic circulation and airway in anesthetized BALB/c mice: PAF, LTC4 and serotonin cause substantial pulmonary vasoconstriction, while histamine biphasic responses of the initial nitric oxide dependent vasodilation followed by vasoconstriction; PAF, serotonin, and histamine, but not LTC4 or PGD2, evoke systemic vasodilatation; only serotonin induces airway constriction. PMID- 26808091 TI - An investigation of the comparability of commercially sourced plasma and pharmaceutical study plasma, using total protein concentration. AB - BACKGROUND: Control blood plasma is regularly used in bioanalysis, biomarkers and proteomics, and is often obtained from commercial sources. It has always been assumed that this plasma will be comparable to plasma drawn during a drug development study. RESULTS: When compared using total protein concentrations, plasma from only one species (dog) demonstrated statistical comparability, plasma from all other species tested (human, rabbit, mouse and rat) shows a statistically significant difference. CONCLUSION: If endogenous components of blood plasma are being measured, or if an assay technique does not significantly limit matrix effects, any assay controls should be prepared using control plasma from the drug development site, or using commercial plasma that has been screened against drug development site plasma. PMID- 26808092 TI - Emotional dysregulation, internalizing symptoms, and self-injurious and suicidal behavior: Structural equation modeling analysis. AB - This study used structural equation modeling to examine the relationships between emotion dysregulation, internalizing symptoms, nonsuicidal self-injury (NSSI), and suicide. One hundred forty-eight undergraduates completed a brief structured interview and self-report measures of emotion dysregulation, internalizing symptoms, and NSSI and suicidal behaviors. Results indicated a significant indirect effect of emotion dysregulation on NSSI via internalizing symptoms and on suicide attempts via NSSI. Findings provide a more nuanced understanding of the indirect association between emotion dysregulation and NSSI and suicidal behaviors. Implications for the potential utility of targeting internalizing symptoms as well as emotion dysregulation in interventions addressing NSSI and suicidal behaviors are discussed. PMID- 26808093 TI - Graphene Ambipolar Nanoelectronics for High Noise Rejection Amplification. AB - In a modern wireless communication system, signal amplification is critical for overcoming losses during multiple data transformations/processes and long distance transmission. Common mode and differential mode are two fundamental amplification mechanisms, and they utilize totally different circuit configurations. In this paper, we report a new type of dual-gate graphene ambipolar device with capability of operating under both common and differential modes to realize signal amplification. The signal goes through two stages of modulation where the phase of signal can be individually modulated to be either in-phase or out-of-phase at two stages by exploiting the ambipolarity of graphene. As a result, both common and differential mode amplifications can be achieved within one single device, which is not possible in the conventional circuit configuration. In addition, a common-mode rejection ratio as high as 80 dB can be achieved, making it possible for low noise circuit application. These results open up new directions of graphene-based ambipolar electronics that greatly simplify the RF circuit complexity and the design of multifunction device operation. PMID- 26808094 TI - Relationship of Body Anthropometry with Cardiovascular Risk Factors in a Random Community Sample: The Phoenix Lifestyle Project. AB - BACKGROUND: We studied the prevalence of metabolic syndrome (MetS) among Indians from a low-income community and evaluated the relationship between physical behavior patterns and anthropometric measures and the presence of MetS. METHODS: The modified WHO STEPS questionnaire was used to collect data from a randomized sample of 1154 subjects from the Indian community of Phoenix, Durban. MetS was classified according to the harmonized criteria. RESULTS: The median age of the sample was 47 (37-55) years, and 72% were predominantly females. There was a high prevalence of elevated body mass index (BMI) in 757 subjects (66%), which increased to 901 subjects (82%) when the ethnic-specific Asian cutoff (BMI >= 23) was applied. Overall increase in waist circumferences was noted from 60% to 79% when ethnic cutoffs were applied. Vigorous exercise was associated with a significant decrease in waist and BMI measurements (P < 0.0001). The prevalence of MetS increased from 30% and 57% (NCEP) to 45% and 60% in males and females, respectively, when the harmonized criteria (IDF and WHO) were applied. Fasting insulin and total cholesterol emerged as independent determinants of MetS for both genders. Neck circumference and HbA1c were also significant predictors of MetS in males. In females, midarm circumference (IDF/WHO) and HbA1c (modified NCEP) emerged as additional predictors of MetS. CONCLUSION: There was a high prevalence of obesity and MetS in this sample, related to sedentary behavior patterns. Neck and arm circumferences as well as total cholesterol may also serve as screening measures to increase the detection rate of MetS. PMID- 26808095 TI - Heterogeneous WSx/WO3 Thorn-Bush Nanofiber Electrodes for Sodium-Ion Batteries. AB - Heterogeneous electrode materials with hierarchical architectures promise to enable considerable improvement in future energy storage devices. In this study, we report on a tailored synthetic strategy used to create heterogeneous tungsten sulfide/oxide core-shell nanofiber materials with vertically and randomly aligned thorn-bush features, and we evaluate them as potential anode materials for high performance Na-ion batteries. The WSx (2 <= x <= 3, amorphous WS3 and crystalline WS2) nanofiber is successfully prepared by electrospinning and subsequent calcination in a reducing atmosphere. To prevent capacity degradation of the WSx anodes originating from sulfur dissolution, a facile post-thermal treatment in air is applied to form an oxide passivation surface. Interestingly, WO3 thorn bundles are randomly grown on the nanofiber stem, resulting from the surface conversion. We elucidate the evolving morphological and structural features of the nanofibers during post-thermal treatment. The heterogeneous thorn-bush nanofiber electrodes deliver a high second discharge capacity of 791 mAh g(-1) and improved cycle performance for 100 cycles compared to the pristine WSx nanofiber. We show that this hierarchical design is effective in reducing sulfur dissolution, as shown by cycling analysis with counter Na electrodes. PMID- 26808096 TI - Efficacy of salicylic acid to reduce Penicillium expansum inoculum and preserve apple fruits. AB - Apples are among the most commonly consumed fruits worldwide. Blue mold (Penicillium expansum) is one of the major diseases in apples postharvest, leading to wide use of fungicides and the search for alternative products to control the pathogen. In this context, this study aimed to evaluate the potential of salicylic acid (SA) as an alternative product to control blue mold and to preserve the physicochemical characteristics of apple fruit postharvest. The antimicrobial effect of SA was determined both in vitro and in situ, by directly exposing conidia to solutions of different concentrations SA or by inoculating the fruit with P. expansum and treating them curatively, eradicatively, or preventively with a 2.5mM SA solution. The physiological effects of SA on fruit were determined by quantifying the weight loss, total soluble solids content, and titratable acidity. In addition, the accumulation of SA in the fruit was determined by HPLC. SA (2.5mM) inhibited 100% of fungal germination in vitro and also controlled blue mold in situ when applied eradicatively. In addition, HPLC analysis demonstrated that SA did not persist in apple fruit. SA also maintained the physicochemical characteristics of fruit of different quality categories. Thus, SA may be an alternative to the commercial fungicides currently used against P. expansum. PMID- 26808097 TI - Is the EQ-5D suitable for use in oncology? An overview of the literature and recent developments. AB - The European Quality of Life-5 Dimensions (EQ-5D) questionnaire is widely used in oncology to generate quality of life weights (utilities). The typical purpose is to inform health economic evaluation studies. The EQ-5D is generally suitable for this purpose; it has shown a reasonable degree of reliability, content validity, construct validity and responsiveness in the majority of the available studies. In situations of doubt, combination with other quality-of-life instruments may be an option. The authors expect that the five-level version of the EQ-5D will gradually replace the three-level version, due to reduced ceiling effects and more appropriate responsiveness. Further research should address the benefits achievable through additional dimensions or patient-based valuation, and the validity of EQ-5D versions for proxy respondents. PMID- 26808098 TI - Sickle cell disease. AB - INTRODUCTION: Sickle cell disease causes chronic haemolytic anaemia, dactylitis, and painful acute crises. It also increases the risk of stroke, organ damage, bacterial infections, and complications of blood transfusion. In sub-Saharan Africa, up to one third of adults are carriers of the defective sickle cell gene, and 1% to 2% of babies are born with the disease. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of pharmaceutical interventions to prevent sickle cell crisis and other acute complications in people with sickle cell disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2015 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 369 studies. After deduplication and removal of conference abstracts, 136 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 99 studies and the further review of 37 full publications. Of the 37 full articles evaluated, three already included systematic reviews were updated, two systematic reviews, two RCTs, and one subsequent RCT were added at this update. We performed a GRADE evaluation for 12 PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for five interventions based on information about the effectiveness and safety of antibiotic prophylaxis in children aged under 5 years, antibiotic prophylaxis in children aged 5 years or older, hydroxyurea, malaria chemoprophylaxis, and pneumococcal vaccines. PMID- 26808100 TI - Food mechanical properties and dietary ecology. AB - Interdisciplinary research has benefitted the fields of anthropology and engineering for decades: a classic example being the application of material science to the field of feeding biomechanics. However, after decades of research, discordances have developed in how mechanical properties are defined, measured, calculated, and used due to disharmonies between and within fields. This is highlighted by "toughness," or energy release rate, the comparison of incomparable tests (i.e., the scissors and wedge tests), and the comparison of incomparable metrics (i.e., the stress and displacement-limited indices). Furthermore, while material scientists report on a myriad of mechanical properties, it is common for feeding biomechanics studies to report on just one (energy release rate) or two (energy release rate and Young's modulus), which may or may not be the most appropriate for understanding feeding mechanics. Here, I review portions of materials science important to feeding biomechanists, discussing some of the basic assumptions, tests, and measurements. Next, I provide an overview of what is mechanically important during feeding, and discuss the application of mechanical property tests to feeding biomechanics. I also explain how 1) toughness measures gathered with the scissors, wedge, razor, and/or punch and die tests on non-linearly elastic brittle materials are not mechanical properties, 2) scissors and wedge tests are not comparable and 3) the stress and displacement-limited indices are not comparable. Finally, I discuss what data gathered thus far can be best used for, and discuss the future of the field, urging researchers to challenge underlying assumptions in currently used methods to gain a better understanding between primate masticatory morphology and diet. PMID- 26808101 TI - Sexual Selection and the differences between the sexes in Mandrills (Mandrillus sphinx). AB - Sexual selection has become a major focus in evolutionary and behavioral ecology. It is also a popular research topic in primatology. I use studies of mandrills (Mandrillus sphinx), a classic example of extravagant armaments and ornaments in animals, to exemplify how a long-term, multidisciplinary approach that integrates field observations with laboratory methods can contribute to on-going theoretical debates in the field of sexual selection. I begin with a brief summary of the main concepts of sexual selection theory and the differences between the sexes. I then introduce mandrills and the study population and review mandrill life history, the ontogeny of sex differences, and maternal effects. Next, I focus on male-male competition and female choice, followed by the less well-studied questions of female-female competition and male choice. This review shows how different reproductive priorities lead to very different life histories and divergent adaptations in males and females. It demonstrates how broadening traditional perspectives on sexual selection beyond the ostentatious results of intense sexual selection on males leads to an understanding of more subtle and cryptic forms of competition and choice in both sexes and opens many productive avenues in the study of primate reproductive strategies. These include the potential for studies of postcopulatory selection, female intrasexual competition, and male choice. These studies of mandrills provide comparison and, I hope, inspiration for studies of both other polygynandrous species and species with mating systems less traditionally associated with sexual selection. PMID- 26808102 TI - Bone morphologies and histories: Life course approaches in bioarchaeology. AB - The duality of the skeleton as both a biological and cultural entity has formed the theoretical basis of bioarchaeology. In recent years bioarchaeological studies have stretched the early biocultural concept with the adoption of life course approaches in their study design and analyses, making a significant contribution to how we think about the role of postnatal plasticity. Life course theory is a conceptual framework used in several scientific fields of biology and the social sciences. Studies that emphasize life course approaches in the examination of bone morphology in the past are united in their interrogation of human life as a result of interrelated and cumulative events over not only the timeframe of individuals, but also over generations at the community level. This article provides an overview of the theoretical constructs that utilize the life course concept, and a discussion of the different ways these theories have been applied to thinking about trajectories of bone morphology in the past, specifically highlighting key recent studies that have used life course approaches to understand the influence of growth, stress, diet, activity, and aging on the skeleton. The goal of this article is to demonstrate the scope of contemporary bioarchaeological studies that illuminate the importance of environmental and behavioral influence on bone morphology. Understanding how trajectories of bone growth and morphology can be altered and shaped over the life course is critical not only for bioarchaeologists, but also researchers studying bone morphology in living nonhuman primates and fossil primate skeletons. PMID- 26808103 TI - Biocultural perspectives on maternal mortality and obstetrical death from the past to the present. AB - Global efforts to improve maternal health are the fifth focus goal of the Millennium Development Goals adopted by the international community in 2000. While maternal mortality is an epidemic, and the death of a woman in childbirth is tragic, certain assumptions that frame the risk of death for reproductive aged women continue to hinge on the anthropological theory of the "obstetric dilemma." According to this theory, a cost of hominin selection to bipedalism is the reduction of the pelvic girdle; in tension with increasing encephalization, this reduction results in cephalopelvic disproportion, creating an assumed fragile relationship between a woman, her reproductive body, and the neonates she gives birth to. This theory, conceived in the 19th century, gained traction in the paleoanthropological literature in the mid-20th century. Supported by biomedical discourses, it was cited as the definitive reason for difficulties in human birth. Bioarchaeological research supported this narrative by utilizing demographic parameters that depict the death of young women from reproductive complications. But the roles of biomedical and cultural practices that place women at higher risk for morbidity and early mortality are often not considered. This review argues that reinforcing the obstetrical dilemma by framing reproductive complications as the direct result of evolutionary forces conceals the larger health disparities and risks that women face globally. The obstetrical dilemma theory shifts the focus away from other physiological and cultural components that have evolved in concert with bipedalism to ensure the safe delivery of mother and child. It also sets the stage for a framework of biological determinism and structural violence in which the reproductive aged female is a product of her pathologized reproductive body. But what puts reproductive aged women at risk for higher rates of morbidity and mortality goes far beyond the reproductive body. Moving beyond reproduction as the root causes of health inequalities reveals gendered-based oppression and inequality in health analyses. In this new model, maternal mortality can be seen as a sensitive indicator of inequality and social development, and can be explored for what it is telling us about women's health and lives. This article reviews the research in pelvic architecture and cephalopelvic relationships from the subfields of evolutionary biology, paleoanthropology, bioarchaeology, medical anthropology, and medicine, juxtaposing it with historical, ethnographic, and global maternal health analyses to offer a biocultural examination of maternal mortality and reproductive risk management. It reveals the structural violence against reproductive aged women inherent in the biomedical management of birth. By reframing birth as normal, not pathological, global health initiatives can consider new policies that focus on larger issues of disparity (e.g., poverty, lack of education, and poor nutrition) and support better health outcomes across the spectrum of life for women globally. PMID- 26808104 TI - The reproductive ecology of iron in women. AB - Reproductive ecology focuses on the sensitivity of human reproduction to environmental variation. While reproductive ecology has historically focused on the relationship between energy status and reproductive outcomes, iron status is equally critical to women's reproductive health, given the wide-ranging detrimental effects of iron-deficiency anemia on maternal and infant well-being. This review interprets the vast literature on iron status and women's reproduction through an evolutionary framework. First, it will critique the evidence for iron deficiency caused by blood loss during menstruation, reinterpreting the available data as ecological variation in menses within and between populations of women. Second, it will highlight the scant but growing evidence that iron status is implicated in fertility, a relationship that has deep evolutionary roots. Third, this review proposes a new hypothesis for the transfer of iron from mother to infant via pregnancy and breastfeeding: reproductive iron withholding. In this hypothesis, mothers transfer iron to infants in a manner that helps infants avoid iron-mediated infection and oxidative stress, but trades off with potential risk of maternal and infant iron deficiency. Finally, this review explores two main factors that can modify the relationship between iron status and the gestation-lactation cycle: (1) the relationship between long-term reproductive effort (parity) and iron status and (2) supplementation schemes before and during pregnancy. The review concludes by suggesting continued research into iron homeostasis in women using evolutionary, ecological, and biocultural frameworks. PMID- 26808105 TI - Vertebral numbers and human evolution. AB - Ever since Tyson (1699), anatomists have noted and compared differences in the regional numbers of vertebrae among humans and other hominoids. Subsequent workers interpreted these differences in phylogenetic, functional, and behavioral frameworks and speculated on the history of vertebral numbers during human evolution. Even in a modern phylogenetic framework and with greatly expanded sample sizes of hominoid species, researchers' conclusions vary drastically, positing that hominins evolved from either a "long-backed" (numerically long lumbar column) or a "short-backed" (numerically short lumbar column) ancestor. We show that these disparate interpretations are due in part to the use of different criteria for what defines a lumbar vertebra, but argue that, regardless of which lumbar definition is used, hominins are similar to their great ape relatives in possessing a short trunk, a rare occurrence in mammals and one that defines the clade Hominoidea. Furthermore, we address the recent claim that the early hominin thoracolumbar configuration is not distinct from that of modern humans and conclude that early hominins show evidence of "cranial shifting," which might explain the anomalous morphology of several early hominin fossils. Finally, we evaluate the competing hypotheses on numbers of vertebrae and argue that the current data support a hominin ancestor with an African ape-like short trunk and lower back. PMID- 26808106 TI - Incorporating the gut microbiota into models of human and non-human primate ecology and evolution. AB - The mammalian gut is home to a diverse community of microbes. Advances in technology over the past two decades have allowed us to examine this community, the gut microbiota, in more detail, revealing a wide range of influences on host nutrition, health, and behavior. These host-gut microbe interactions appear to shape host plasticity and fitness in a variety of contexts, and therefore represent a key factor missing from existing models of human and non-human primate ecology and evolution. However, current studies of the gut microbiota tend to include limited contextual data or are clinical, making it difficult to directly test broad anthropological hypotheses. Here, I review what is known about the animal gut microbiota and provide examples of how gut microbiota research can be integrated into the study of human and non-human primate ecology and evolution with targeted data collection. Specifically, I examine how the gut microbiota may impact primate diet, energetics, disease resistance, and cognition. While gut microbiota research is proliferating rapidly, especially in the context of humans, there remain important gaps in our understanding of host gut microbe interactions that will require an anthropological perspective to fill. Likewise, gut microbiota research will be an important tool for filling remaining gaps in anthropological research. PMID- 26808107 TI - Identifications of ancient Egyptian royal mummies from the 18th Dynasty reconsidered. AB - For centuries, ancient Egyptian Royal mummies have drawn the attention both of the general public and scientists. Many royal mummies from the New Kingdom have survived. The discoveries of the bodies of these ancient rulers have always sparked much attention, yet not all identifications are clear even nowadays. This study presents a meta-analysis to demonstrate the difficulties in identifying ancient Egyptian royal mummies. Various methods and pitfalls in the identification of the Pharaohs are reassessed since new scientific methods can be used, such as ancient DNA-profiling and CT-scanning. While the ancestors of Tutankhamun have been identified, some identities are still highly controversial (e.g., the mystery of the KV-55 skeleton, recently most likely identified as the genetic father of Tutankhamun). The meta-analysis confirms the suggested identity of some mummies (e.g., Amenhotep III, Thutmosis IV, and Queen Tjye). PMID- 26808109 TI - Preface. PMID- 26808108 TI - Accepting, understanding, teaching, and learning (human) evolution: Obstacles and opportunities. AB - Questions about our origin as a species are universal and compelling. Evolution and in particular human evolution-is a subject that generates intense interest across the world, evidenced by the fact that fossil and DNA discoveries grace the covers of major science journals and magazines as well as other popular print and online media. However, virtually all national polls indicate that the majority of Americans strongly reject biological evolution as a fact-based, well-tested, and robust understanding of the history of life. In the popular mind, no topic in all of science is more contentious or polarizing than evolution and media sources often only serve to magnify this polarization by covering challenges to the teaching of evolution. In the realm of teaching, debates about evolution have shaped textbooks, curricula, standards, and policy. Challenges to accepting and understanding evolution include mistrust and denial of science, cognitive obstacles and misconceptions, language and terminology, and a religious worldview, among others. Teachers, who are on the front lines of these challenges, must be armed with the tools and techniques to teach evolution in formal education settings across grades K-16 in a straightforward, thorough, and sensitive way. Despite the potentially controversial topic of human evolution, growing research is demonstrating that a pedagogical focus on human examples is an effective and engaging way to teach core concepts of evolutionary biology. PMID- 26808110 TI - Hominin taxic diversity: Fact or fantasy? AB - In this review of the evidence for and against taxic diversity within the hominin clade, we begin by looking at the logic and the history of simple "ladder-like" interpretations of the hominin fossil record. We then look at the hominin fossil record in a series of time intervals and use current published evidence about the first and last appearance dates of each taxon to decide whether a species or specimens should be included in one, or more, of the intervals. Within each time interval, we consider the strength of the evidence that more than one hominin species is sampled. Decisions about whether taxonomic diversity exists depend on what alpha taxonomic hypotheses are used and although we use a relatively speciose interpretation of the hominin fossil record, we also explore what impact more inclusive interpretations of alpha taxonomy would have on assessments of hominin taxic diversity. With the exception of the oldest (7-5 Ma) all of the other time intervals have in our judgment at least one well-supported example of taxic diversity and several have multiple examples. In summary, not all new hominin taxa are created equally, but while taxic diversity may not be as prevalent as some have claimed, it is a feature of the hominin clade from 4 Ma until c.40 ka years ago. PMID- 26808111 TI - The evolutionary origin and population history of the grauer gorilla. AB - Gorillas living in western central Africa (Gorilla gorilla) are morphologically and genetically distinguishable from those living in eastern central Africa (Gorilla beringei). Genomic analyses show eastern gorillas experienced a significant reduction in population size during the Pleistocene subsequent to geographical isolation from their western counterparts. However, how these results relate more specifically to the recent biogeographical and evolutionary history of eastern gorillas remains poorly understood. Here we show that two rare morphological traits are present in the hands and feet of both eastern gorilla subspecies at strikingly high frequencies (>60% in G. b. graueri; ~28% in G. b. beringei) in comparison with western gorillas (<1%). The intrageneric distribution of these rare traits suggests that they became common among eastern gorillas after diverging from their western relatives during the early to middle Pleistocene. The extremely high frequencies observed among grauer gorillas-which currently occupy a geographic range more than ten times the size of that of mountain gorillas-imply that grauers originated relatively recently from a small founding population of eastern gorillas. Current paleoenvironmental, geological, and biogeographical evidence supports the hypothesis that a small group of eastern gorillas likely dispersed westward from the Virungas into present-day grauer range in the highlands just north of Lake Kivu, either immediately before or directly after the Younger Dryas interval. We propose that as the lowland forests of central Africa expanded rapidly during the early Holocene, they became connected with the expanding highland forests along the Albertine Rift and enabled the descendants of this small group to widely disperse. The descendant populations significantly expanded their geographic range and population numbers relative to the gorillas of the Virunga Mountains and the Bwindi-Impenetrable Forest, ultimately resulting in the grauer gorilla subspecies recognized today. This founder-effect hypothesis offers some optimism for modern conservation efforts to save critically endangered eastern gorillas from extinction. PMID- 26808112 TI - Genes with monoallelic expression contribute disproportionately to genetic diversity in humans. AB - An unexpectedly large number of human autosomal genes are subject to monoallelic expression (MAE). Our analysis of 4,227 such genes uncovers surprisingly high genetic variation across human populations. This increased diversity is unlikely to reflect relaxed purifying selection. Remarkably, MAE genes exhibit an elevated recombination rate and an increased density of hypermutable sequence contexts. However, these factors do not fully account for the increased diversity. We find that the elevated nucleotide diversity of MAE genes is also associated with greater allelic age: variants in these genes tend to be older and are enriched in polymorphisms shared by Neanderthals and chimpanzees. Both synonymous and nonsynonymous alleles of MAE genes have elevated average population frequencies. We also observed strong enrichment of the MAE signature among genes reported to evolve under balancing selection. We propose that an important biological function of widespread MAE might be the generation of cell-to-cell heterogeneity; the increased genetic variation contributes to this heterogeneity. PMID- 26808114 TI - Clinicopathological factors predictive of postoperative seizures in patients with gliomas. AB - PURPOSE: Epilepsy is one of the most common manifestations in gliomas and has a severe effect on the life expectancy and quality of life of patients. The aim of our study was to assess the potential connections between clinicopathological factors and postoperative seizure. METHOD: We retrospectively investigated a group of 147 Chinese high-grade glioma (HGG) patients with preoperative seizure to examine the correlation between postoperative seizure and clinicopathological factors and prognosis. Univariate analyses and multivariate logistic regression analyses were performed to identify factors associated with postoperative seizures. Survival function curves were calculated using the Kaplan-Meier method. RESULTS: 53 patients (36%) were completely seizure-free (Engel class I), and 94 (64%) experienced a postoperative seizure (Engel classes II, III, and IV). A Chi squared analysis showed that anaplastic oligodendroglioma/anaplastic oligoastrocytoma (AO/AOA) (P=0.05), epidermal growth factor receptor (EGFR) expression (P=0.0004), O(6)-methylguanine DNA methyltransferase (MGMT) expression (P=0.011), and phosphatase and tensin homolog (PTEN) expression (P=0.045) were all significantly different. A logistic regression analysis showed that MGMT expression (P=0.05), EGFR expression (P=0.001), and AO/AOA (P=0.038) are independent factors of postoperative seizure. Patients with lower MGMT and EGFR expression and AO/AOA showed more frequent instances of postoperative seizure. Postoperative seizure showed no statistical significance on overall survival (OS) and progression-free survival (PFS). CONCLUSION: Our study identified clinicopathological factors related to postoperative seizure in HGGs and found two predictive biomarkers of postoperative seizure: MGMT and EGFR. These findings provided insight treatment strategies aimed at prolonging survival and improving quality of life. PMID- 26808115 TI - In Situ Packaging FeFx into Sack-like Carbon Nanoreactors: A Smart Way To Make Soluble Fluorides Applicable to Aqueous Batteries. AB - Ferruginous materials have long attracted great interest in aqueous batteries since Fe is an earth-abundant and low toxic element. However, their practical application is severely hindered by their poor structural stability during deep cycling. To maximize their cyclability, we herein propose a simple and effective method, by in situ packaging Fe-based materials into carbon nanosacks via a facile CVD approach. To verify our strategy, we purposely choose water-soluble Fe2F5 as a study paradigm. The in situ formed Fe2F5@C nanosacks product exhibits prominent anodic performance with high electrochemical activity and capacity, obviously prolonged cyclic lifetime, and outstanding rate capabilities. Besides, by pairing with the cathode of alpha-Co(OH)2 nanowire arrays@carbon cloth, a full device of rechargeable aqueous batteries has been developed, capable to deliver both high specific energy and power densities (Max. values reaching up to ~163 Wh kg(-1) and ~14.2 kW kg(-1)), which shows great potential in practical usage. Our present work may not only demonstrate the feasibility of using soluble fluorides as anodes for aqueous batteries but also provide a smart way to upgrade cyclic behaviors of Fe-based anodes. PMID- 26808116 TI - National Prehospital Evidence-Based Guidelines Strategy: A Summary for EMS Stakeholders. AB - Multiple national organizations have recommended and supported a national investment to increase the scientific evidence available to guide patient care delivered by Emergency Medical Services (EMS) and incorporate that evidence directly into EMS systems. Ongoing efforts seek to develop, implement, and evaluate prehospital evidence-based guidelines (EBGs) using the National Model Process created by a multidisciplinary panel of experts convened by the Federal Interagency Committee on EMS (FICEMS) and the National EMS Advisory Council (NEMSAC). Yet, these and other EBG efforts have occurred in relative isolation, with limited direct collaboration between national projects, and have experienced challenges in implementation of individual guidelines. There is a need to develop sustainable relationships among stakeholders that facilitate a common vision that facilitates EBG efforts. Herein, we summarize a National Strategy on EBGs developed by the National Association of EMS Physicians (NAEMSP) with involvement of 57 stakeholder organizations, and with the financial support of the National Highway Traffic Safety Administration (NHTSA) and the EMS for Children program. The Strategy proposes seven action items that support collaborative efforts in advancing prehospital EBGs. The first proposed action is creation of a Prehospital Guidelines Consortium (PGC) representing national medical and EMS organizations that have an interest in prehospital EBGs and their benefits to patient outcomes. Other action items include promoting research that supports creation and evaluates the impact of EBGs, promoting the development of new EBGs through improved stakeholder collaboration, and improving education on evidence based medicine for all prehospital providers. The Strategy intends to facilitate implementation of EBGs by improving guideline dissemination and incorporation into protocols, and seeks to establish standardized evaluation methods for prehospital EBGs. Finally, the Strategy proposes that key stakeholder organizations financially support the Prehospital Guidelines Consortium as a means of implementing the Strategy, while together promoting additional funding for continued EBG efforts. PMID- 26808113 TI - High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry. AB - Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,478 SLE cases and 12,656 controls from six East Asian cohorts to identify new SLE susceptibility loci and better localize known loci. We identified ten new loci and confirmed 20 known loci with genome-wide significance. Among the new loci, the most significant locus was GTF2IRD1-GTF2I at 7q11.23 (rs73366469, Pmeta = 3.75 * 10(-117), odds ratio (OR) = 2.38), followed by DEF6, IL12B, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6. We identified the most likely functional variants at each locus by analyzing epigenetic marks and gene expression data. Ten candidate variants are known to alter gene expression in cis or in trans. Enrichment analysis highlights the importance of these loci in B cell and T cell biology. The new loci, together with previously known loci, increase the explained heritability of SLE to 24%. The new loci share functional and ontological characteristics with previously reported loci and are possible drug targets for SLE therapeutics. PMID- 26808117 TI - Controlling Peptide Self-Assembly through a Native Chemical Ligation/Desulfurization Strategy. AB - Self-assembled peptides were synthesized by using a native chemical ligation (NCL)/desulfurization strategy that maintained the chemical diversity of the self assembled peptides. Herein, we employed oxo-ester-mediated NCL reactions to incorporate cysteine, a cysteine-based dipeptide, and a sterically hindered unnatural amino acid (penicillamine) into peptides. Self-assembly of the peptides resulted in the formation of self-supporting gels. Microscopy analysis indicated the formation of helical nanofibers, which were responsible for the formation of gel matrices. The self-assembly of the ligated peptides was governed by covalent and non-covalent interactions, as confirmed by FTIR, CD, fluorescence spectroscopy, and MS (ESI) analyses. Peptide disassembly was induced by desulfurization reactions with tris(2-carboxyethyl)phosphine (TCEP) and glutathione at 80 degrees C. Desulfurization reactions of the ligated peptides converted the Cys and penicillamine functionalities into Ala and Val moieties, respectively. The self-supporting gels showed significant shear-thinning and thixotropic properties. PMID- 26808118 TI - Ag doped hollow TiO2 nanoparticles as an effective green fungicide against Fusarium solani and Venturia inaequalis phytopathogens. AB - Chemical-based pesticides are widely used in agriculture to protect crops from insect infestation and diseases. However, the excessive use of highly toxic pesticides causes several human health (neurological, tumor, cancer) and environmental problems. Therefore nanoparticle-based green pesticides have become of special importance in recent years. The antifungal activities of pure and Ag doped (solid and hollow) TiO2 nanoparticles are studied against two potent phytopathogens, Fusarium solani (which causes Fusarium wilt disease in potato, tomato, etc) and Venturia inaequalis (which causes apple scab disease) and it is found that hollow nanoparticles are more effective than the other two. The antifungal activities of the nanoparticles were further enhanced against these two phytopathogens under visible light exposure. The fungicidal effect of the nanoparticles depends on different parameters, such as particle concentration and the intensity of visible light. The minimum inhibitory dose of the nanoparticles for V. inaequalis and F. solani are 0.75 and 0.43 mg/plate. The presence of Ag as a dopant helps in the formation of stable Ag-S and disulfide bonds (R-S-S-R) in cellular protein, which leads to cell damage. During photocatalysis generated (*)OH radicals loosen the cell wall structure and this finally leads to cell death. The mechanisms of the fungicidal effect of nanoparticles against these two phytopathogens are supported by biuret and triphenyl tetrazolium chloride analyses and field emission electron microscopy. Apart from the fungicidal effect, at a very low dose (0.015 mg/plate) the nanoparticles are successful in arresting production of toxic napthoquinone pigment for F. solani which is related to the fungal pathogenecity. The nanoparticles are found to be effective in protecting potatoes affected by F. solani or other fungi from spoiling. PMID- 26808120 TI - Coral snake bites (Micrurus spp.) in Brazil: a review of literature reports. AB - CONTEXT: In the Americas, the main representatives of the family Elapidae are coral snakes of the genus Micrurus, of which 33 species are in Brazil. They are the smallest cause of venomous snakebite in Brazil. We analyzed literature reports of coral snake bites in Brazil from 1867 to 2014, and provide a brief review of case series and reports of coral snake bites in the Americas in general. METHODS: Only reports with clinical descriptions of envenomation were included. The variables recorded included identification of the offending snake, patient's age, sex, bite site, clinical manifestations, treatment, including antivenom and anticholinesterase drugs, and general evolution of the cases. 30 published reports describing bites caused by Micrurus spp. in Brazil were identified and involved 194 distinct cases. Since no information on the clinical manifestations was available in 44 cases, the analysis was restricted to 25 reports (150 cases). RESULTS: Most patients were from southern (61.3%; primarily Santa Catarina state, 60%) and southeastern (20%) Brazil and were male (70.7%), with a median age of 27 years (interquartile interval = 18 to 40 years). The offending snakes were described in 59 cases (M. corallinus 36, M. frontalis 12, M. lemniscatus 5, M. hemprichi 2, M. filiformis 1, M. ibiboboca 1, M. spixii 1 and M. surinamensis 1); in 22 cases only the genus (Micrurus spp.) was reported. Of the 143 cases in which the bite site was recorded, most involved the hands (46.2%) and feet (26.6%). The main clinical features were local numbness/paresthesia (52.7%), local pain (48%), palpebral ptosis (33.3%), dizziness (26.7%), blurred vision (20.7%), weakness (20%), slight local edema (16%), erythema (16%), dysphagia (14.7%), dyspnea (11.3%), inability to walk (10.7%), myalgia (9.3%), salivation (8%) and respiratory failure (4.3%). Fang marks were described in 47.3% of cases and 14% of bites were classified as asymptomatic. A slight increase in total blood creatine kinase was reported in 3 children, suggesting mild myotoxicity. Therapeutic procedures included coral snake antivenom (77.3%), anticholinesterase drugs (6%), and mechanical ventilation (3.3%). Two patients reported in 1933 developed paralysis/respiratory failure and died 6 h and 17 h post-bite. Four more deaths probably caused by coral snakes were reported (2 in 1867, 1 in 1959, 1 in 1962), but no clinical information was available. DISCUSSION: Neuromuscular blockade was the hallmark of systemic envenomation by Micrurus spp., with signs of myasthenia such as weakness and ptosis that may evolve to paralysis and respiratory failure. Local features, mainly numbness/paresthesia and pain, were frequently reported, with the pain being intense in some cases. Although myotoxicity has been detected in experimental studies with Micrurus spp. venoms, few human reports described laboratory findings compatible with myotoxicity. CONCLUSION: Most coral snake bites reported in Brazil were caused by M. corallinus and M. frontalis, with several patients showing signs of acute myasthenia. Serious complications such as paralysis with respiratory failure were observed but comparatively rare. The deaths occurred where respiratory support (mechanical ventilation) was unavailable when needed. PMID- 26808121 TI - Long-Term Drug-Free Remission and Visual Outcomes in Sympathetic Ophthalmia. AB - PURPOSE: To assess corticosteroid- and immunosuppressive therapy (IST)-free long term remission in the treatment of patients with sympathetic ophthalmia (SO), a vision-robbing disease that can span a lifetime. METHODS: The medical records of 19 patients with SO aged 16.1 to 94.95 years (median age 58.56 years) with median follow-up of 7.10 years (mean, 6.41; range, 2.5 to 8.63 years) were retrospectively examined. RESULTS: All patients achieved control of inflammation, 13 of them for 2 years or more. Three (15.78%) of the 19 patients maintained remission without IST and corticosteroids for more than 5 years with vision of 20/25 or better in the sympathizing eye. Thirteen patients (68.42%) were inactive on IST or corticosteroids or in combination therapy. Eleven patients (57.9%) maintained visual acuity of 20/40 or better at the end of follow-up. CONCLUSION: Even with a devastating and possibly lifelong disease like sympathetic ophthalmia, long-term remission off all IST and corticosteroids, and perhaps even cure, is possible. PMID- 26808122 TI - Adenoviral Mediated Expression of BMP2 by Bone Marrow Stromal Cells Cultured in 3D Copolymer Scaffolds Enhances Bone Formation. AB - Selection of appropriate osteoinductive growth factors, suitable delivery method and proper supportive scaffold are critical for a successful outcome in bone tissue engineering using bone marrow stromal cells (BMSC). This study examined the molecular and functional effect of a combination of adenoviral mediated expression of bone morphogenetic protein-2 (BMP2) in BMSC and recently developed and characterized, biodegradable Poly(L-lactide-co-e-caprolactone){poly(LLA-co CL)}scaffolds in osteogenic molecular changes and ectopic bone formation by using in vitro and in vivo approaches. Pathway-focused custom PCR array, validation using TaqMan based quantitative RT-PCR (qRT-PCR) and ALP staining showed significant up-regulation of several osteogenic and angiogenic molecules, including ALPL and RUNX2 in ad-BMP2 BMSC group grown in poly(LLA-co-CL) scaffolds both at 3 and 14 days. Micro CT and histological analyses of the subcutaneously implanted scaffolds in NOD/SCID mice revealed significantly increased radiopaque areas, percentage bone volume and formation of vital bone in ad-BMP2 scaffolds as compared to the control groups both at 2 and 8 weeks. The increased bone formation in the ad-BMP2 group in vivo was paralleled at the molecular level with concomitant over-expression of a number of osteogenic and angiogenic genes including ALPL, RUNX2, SPP1, ANGPT1. The increased bone formation in ad-BMP2 explants was not found to be associated with enhanced endochondral activity as evidenced by qRT-PCR (SOX9 and FGF2) and Safranin O staining. Taken together, combination of adenoviral mediated BMP-2 expression in BMSC grown in the newly developed poly(LLA-co-CL) scaffolds induced expression of osteogenic markers and enhanced bone formation in vivo. PMID- 26808123 TI - The inhibitory effects of phenolic Mannich bases on carbonic anhydrase I and II isoenzymes. AB - Phenolic mono Mannich bases [2-[4-hydroxy-3-(aminomethyl)benzylidene]-2,3-dihydro 1H-inden-1-one (8-15)] and bis Mannich bases [2-[4-hydroxy-3,5 bis(aminomethyl)benzylidene]-2, 3-dihydro-1H-inden-1-one (2-7)] were synthesized starting from 2-(4-hydroxybenzylidene)-2, 3-dihydro-inden-1-one (1). This study was designed in order to investigate the carbonic anhydrase (CA, EC 4.2.1.1) inhibitory properties of a library of compounds incorporating the phenol functional group. All prepared compounds showed a low inhibition percentages on both human (h) isoforms hCA I and hCA II compared to the reference sulfonamide acetazolamide. Mannich bases 2-15 had lower inhibition percentages than the compound 1 on hCA I and hCA II, except compound 14, which is a Mannich base derivative of dipropylamine, which had a similar inhibitory power as compound 1 on hCA II. All compounds synthesized 1-15 were 1.3-1.9 times more effective on hCA II comparing with the effectivenes of the compounds on hCA I. PMID- 26808119 TI - Vitamin C: the known and the unknown and Goldilocks. AB - Vitamin C (Ascorbic Acid), the antiscorbutic vitamin, cannot be synthesized by humans and other primates, and has to be obtained from diet. Ascorbic acid is an electron donor and acts as a cofactor for fifteen mammalian enzymes. Two sodium dependent transporters are specific for ascorbic acid, and its oxidation product dehydroascorbic acid is transported by glucose transporters. Ascorbic acid is differentially accumulated by most tissues and body fluids. Plasma and tissue vitamin C concentrations are dependent on amount consumed, bioavailability, renal excretion, and utilization. To be biologically meaningful or to be clinically relevant, in vitro and in vivo studies of vitamin C actions have to take into account physiologic concentrations of the vitamin. In this paper, we review vitamin C physiology; the many phenomena involving vitamin C where new knowledge has accrued or where understanding remains limited; raise questions about the vitamin that remain to be answered; and explore lines of investigations that are likely to be fruitful. PMID- 26808125 TI - Clinicopathologic and Prognostic Significance of Metalloproteinase Tissue Inhibitor-2 Promoters in Tunisian Colorectal Cancer: A Case-Control Study. AB - Tissue inhibitors of metalloproteinases (TIMPs) appear to affect many aspects of cancer biology, playing a crucial role in cell signaling by regulating cell growth, apoptosis, invasion, metastasis, angiogenesis, and genomic instability. In the present study, we investigate whether TIMP-2 SNP, TIMP-2 mRNAs, and TIMP-2 protein is associated with susceptibility to colorectal cancer (CRC) in Tunisian population. Taqman and DNA sequencing techniques were used for genotyping, TIMP-2 expression of each genotype was analyzed using semiquantitative RT-PCR and TIMP-2 protein expression was analyzed using immunohistochemistry staining. Our results showed that significantly elevated CRC risk was found in individuals with CC genotype (odds ratio 1.959; 95% confidence interval, 1.055-3.637). Moreover TIMP 2 mRNA expression in the colorectal cell carcinomas was significantly higher compared with the normal colorectal tissue (0.487+/-0.015 vs. 0.210+/-0.013) (P<0.05). In addition, serum levels of TIMP-2 were significantly lower in CRC patients than in adenoma patients (P=0.01) and healthy controls (P=0.003). Serum levels of TIMP-2 correlated significantly with tumor stage and TNM stage and were the lowest in CRC patients with stage D,T4,(N1,N2,N3),M(+). In conclusion, our study demonstrate for the first time the distribution and the clinical significance of TIMP-2 promoter polymorphisms, mRNA, protein expression, and serum level in CRC Tunisian patients suggesting that the genotyping and serum level of TIMP-2 as potential markers for susceptibility to CRC will allow a precise and early identification of individuals at high risk and will aid the design of therapeutic modalities and evaluation of treatment outcome. PMID- 26808124 TI - Coenzyme Q Biosynthesis: Evidence for a Substrate Access Channel in the FAD Dependent Monooxygenase Coq6. AB - Coq6 is an enzyme involved in the biosynthesis of coenzyme Q, a polyisoprenylated benzoquinone lipid essential to the function of the mitochondrial respiratory chain. In the yeast Saccharomyces cerevisiae, this putative flavin-dependent monooxygenase is proposed to hydroxylate the benzene ring of coenzyme Q (ubiquinone) precursor at position C5. We show here through biochemical studies that Coq6 is a flavoprotein using FAD as a cofactor. Homology models of the Coq6 FAD complex are constructed and studied through molecular dynamics and substrate docking calculations of 3-hexaprenyl-4-hydroxyphenol (4-HP6), a bulky hydrophobic model substrate. We identify a putative access channel for Coq6 in a wild type model and propose in silico mutations positioned at its entrance capable of partially (G248R and L382E single mutations) or completely (a G248R-L382E double mutation) blocking access to the channel for the substrate. Further in vivo assays support the computational predictions, thus explaining the decreased activities or inactivation of the mutated enzymes. This work provides the first detailed structural information of an important and highly conserved enzyme of ubiquinone biosynthesis. PMID- 26808126 TI - Comprehensive Histologic Scoring to Maximize the Predictability of Pathology generated Equation of Breast Cancer Oncotype DX Recurrence Score. AB - BACKGROUND: Pathology-generated equations have been introduced to predict Oncotype DX recurrence score (ORS) in breast cancer. The purpose of the study is to improve these equations. MATERIALS AND METHODS: Slides from 416 (test set) consecutive breast cancers with available Oncotype DX were reviewed. A validation set (n=91) was prospectively scored using the generated formulas from the test set. The following histopathologic features were graded: Nottingham grade (designated as current Nottingham grade), necrosis, and degree of tumor infiltrating lymphocytes. The following data were extracted from the pathology report: Nottingham grade (designated as reported Nottingham grade), tumor size, ER/PR Allred scores, HER2 status, and ORS. Equations were calculated, one included the reported Nottingham grade, one included the current Nottingham grade, and one included the current Nottingham grade with the other significant histopathologic variables. RESULTS: In the equation that included the reported Nottingham grade, ER, PR, and HER2, the overall concordance with the ORS was 64.86%. After excluding the intermediate category detected by the formula, the concordance rate was 95.28%. When the current Nottingham grade was included, the concordance rate became 69.61% and 98.62%, respectively. When necrosis and the degree of tumor-infiltrating lymphocytes were added to the previous equation, these rates became 70.1% and 98.63%, respectively. CONCLUSIONS: Our equation has better correlation with ORS than previously published results. PMID- 26808127 TI - Breast Carcinoma-associated Fibroblasts Share Similar Biomarker Profiles in Matched Lymph Node Metastasis. AB - This study sought to understand the role of breast carcinoma-associated fibroblasts in the progression of cancer cells into lymph nodes. We compared fibroblasts of primary tumors and matched the involved lymph nodes to select fibroblast activation markers, namely alpha-smooth muscle actin (alpha-SMA), S100A4, and vimentin, as well as to determine the frequency of transforming growth factor beta1, a pleiotropic cytokine that induces the differentiation of fibroblasts to myofibroblasts, and its downstream effectors: CXCR4 and p-AKT. We disposed samples of 80 primary invasive ductal carcinomas and matched the involved lymph nodes from 43 cases into 3 tissue microarrays, and analyzed stromal and tumor epithelial cells separately by immunohistochemistry. Control uninvolved lymph nodes were analyzed by whole-tissue sections. Cancer-associated fibroblast in lymph nodes with macrometastasis expressed similar profiles of vimentin, alpha-SMA, and S100A4 as those found in primary tumors. Cancer associated fibroblast were uniformly estrogen receptor, progesterone receptor, HER-2, Ki-67, and p53 negative, but expressions of transforming growth factor beta1 (TGFbeta1), CXCR4, and p-AKT staining (62.3%, 52.4%, 65%, respectively) were equivalent between primary and lymph node metastasis (LNM) fibroblasts. A significant coexpression of TGFbeta1 with p-AKT and CXCR4 in LNMs suggested the involvement of these proteins with TGFbeta1 signaling. These biomarkers, including alpha-SMA and S100A4, were negative in fibroblasts of cancer-free lymph nodes, with the exception of vimentin. Our finding that expressions of biological markers were similar in fibroblasts of the primary tumors and in matched LNMs, but were absent in cancer-free lymph nodes, supports the assumption that the lymph node stroma mimics the microenvironment observed in primary tumors. PMID- 26808128 TI - Granuloma Faciale and Eosinophilic Angiocentric Fibrosis: Similar Entities in Different Anatomic Sites. AB - BACKGROUND: Eosinophilic angiocentric fibrosis (EAF) and granuloma faciale (GF) share several histopathologic features, including eosinophil-rich inflammation, microangiitis, and progressive fibrosis. Concurrent presentation of EAF and GF suggests a pathogenetic link between them. OBJECTIVES: To identify histologic findings that tell them apart and construe the pathogenetic mechanisms behind each morphologic variable, 14 immunohistochemical markers were used to study the cells subpopulations in 14 cases of GF and 3 cases of EAF. MATERIALS AND METHODS: The lesions were classified according to their stage of development. The antibodies studied were: CD4, Foxp3, CD8, granzymes A and B, perforin, granulysin, CD20, CD56, CD68, ICAM-1, CD34, CD105, and 1A4. RESULTS: The intensity of the sclerotic response and the density of 1A4-immunostained cells were significantly higher in EAF. In both diseases, CD68 cells were the most numerous, followed by CD20, CD8, and CD4 cells. About 30% of cells expressed ICAM 1. Among cells with cytotoxic granules, granulysin-positive cells were the most frequent. CONCLUSIONS: Differences between GF and EAF were found to be mostly like due to anatomic site (usually skin of the face vs. sinonasal cavity) and stage of the disease development (usually earlier in cutaneous lesions because of their visibility). Innate and adaptive immunity, including B cells, T cells, and cytotoxic granules have a role in their pathogenesis. PMID- 26808129 TI - Two Cases of Chronic Intestinal Pseudo-obstruction: A Comparison of Staining Characteristics of Enteric Visceral Myopathy With Hirschsprung Disease. AB - Chronic intestinal pseudo-obstruction (CIPO), a rare, debilitating disorder of bowel motility dysfunction, is largely a clinical diagnosis, without any universally accepted diagnostic criteria. Three subgroups are generally acknowledged based on the cell-type affected: enteric visceral myopathy (the most common subgroup), neuropathy, and mesenchymopathy. A fourth subgroup includes abnormalities of neurohormonal peptides. Although immunohistochemical staining is reportedly useful for identifying the mesenchymopathic type, its role in diagnosing enteric visceral myopathy and neuropathy has been fraught with difficulties. We present two cases of chronic intestinal pseudo-obstruction that are clinically and histopathologically suggestive of type III visceral enteric myopathy, aiming to expound upon the diagnostic and pathogenic features. We found that the outer-longitudinal layer of the muscularis propria was more severely affected as compared with the inner circular layer. To investigate the value of this finding, we performed immunostains in the one case in which a paraffin block was available. We found increased peripherin and calretinin immunopositive nerve fibers in the outer layer as compared with inner, but without any significant increase in S-100 positivity or alteration in neuronal morphology of myenteric plexus, a novel finding. This differential staining pattern was completely different from Hirschsprung disease, in which we found rare to absent peripherin and calretinin staining. It is unclear if this increase in the outer layer in visceral myopathy reflects a reactive change or dysfunctional axons. In addition, the history of volvulus in one patient and transmural inflammatory changes in the second raise concerns about the higher propensity of clinical complications secondary to the attenuated outer muscular layer. This study suggests that enteric visceral myopathy has histologic and staining characteristics different from Hirschsprung disease, a finding of diagnostic significance in the differential diagnosis of bowel obstruction. Moreover, these features may have pathogenic value and need further confirmation. PMID- 26808130 TI - Reduced E-Cadherin and Aberrant beta-Catenin Expression are Associated With Advanced Disease in Signet-Ring Cell Carcinomas. AB - Signet-ring cell carcinomas (SRCCs) tend to present at higher stages and thus are generally associated with a worse prognosis. It has been postulated that a deficiency of E-cadherin may be causal in the pathogenesis of SRCC in animal models. In this study, we systemically analyzed the expression of E-cadherin and beta-catenin, a key component of the cadherin complex, in 137 consecutive SRCCs of various organ systems to explore the significance of these molecules in the pathogenesis and progression of SRCCs. Seventy-six percent of SRCCs showed loss or reduced E-cadherin expression. Aberrant beta-catenin expression, defined as loss of membranous expression and nuclear/cytoplasmic subcellular localization, was observed in 60% of these cases, with the altered beta-catenin expression observed most commonly in the breast (93%) and least in the lung (38%) primaries. Further, the aberrant beta-catenin was significantly associated with pathologic nodal stage (P=0.002) and clinical stage (P=0.02). Our findings demonstrated that reduced membranous E-cadherin and aberrant beta-catenin expression were frequent events in SRCCs of various organs, and that the altered beta-catenin expression was significantly associated with advanced disease. The observations further support the importance of these molecules in the pathogenesis of SRCCs, and indicate the fundamental role of the Wnt/beta-catenin signaling pathway in the progression of these tumors. Further investigations of the downstream molecules in this cascade may provide potential novel therapeutic targets for this aggressive tumor type. PMID- 26808131 TI - A New Hitherto Unreported Histopathologic Manifestation of Mammary Analogue Secretory Carcinoma: "Masked MASC" Associated With Low-grade Mucinous Adenocarcinoma and Low-grade In Situ Carcinoma Components. AB - We present a salivary gland tumor of the parotid gland in a 54-year-old woman, which contained a minor mammary analogue secretory carcinoma (MASC) component (20%) intermixed with a morphologically entirely different mucinous adenocarcinomatous component that comprised 80% of the tumor mass and a morphologically nondescript low-grade intraductal carcinoma (in situ) component. On fluorescence in situ hybridization, a break in the ETV6 gene was documented in the mucinous adenocarcinomatous, the conventional MASC, and the intraductal (in situ) components. RT-PCR failed to reveal an ETV6-NTRK3 fusion. The entire conventional MASC and only rare mucinous adenocarcinoma tumor cells were mammaglobin positive, whereas the low-grade intraductal carcinoma (in-situ) component was negative. S-100 protein stained only the MASC component. PMID- 26808132 TI - D2-40 Antibody is a Specific Marker for B2 Thymomas. AB - The correlation between the worse outcome of thymomas and expression of podoplanin (D2-40 antibody) in neoplastic cells has been proved in recent studies. We investigated the expression of podoplanin in thymic epithelial tumors of different histologic types and stages resected in our institution. The presence and type of reaction (membranous or cytoplasmic) with D2-40 antibody were assessed. Analyzed group consisted of 72 tumors: 3 type A, 19 type AB, 5 type B1, 24 type B2, 4 type B3, 2 micronodular, 1 metaplastic, and 9 combined B2B3 thymomas and 5 thymic carcinomas. Positive reaction with D2-40 was detected in 7 cases (37%) of AB type, 2 (40%) of B1, 28 (85%) of B2, 3 (23%) of B3, and 1 case (100%) of metaplastic thymoma. All positive B2 and 2 cases of B3 thymomas revealed membranous type of reaction, whereas other subtypes showed less conspicuous cytoplasmic reactivity. A correlation between B2 thymoma and membranous type of reaction was statistically significant (P<0.0001). There was also a slight relationship between cytoplasmic type of reaction and AB or B1 thymomas (P=0.0256). No correlation was detected between D2-40-reactivity and stage (P=0.4) or myasthenic symptoms (P=0.21). In conclusion, membranous type of reaction with D2-40 antibody in thymomas is highly specific for B2 subtype, but antipodoplanin immunoreactivity has no relationship with the tumor stage. PMID- 26808133 TI - Application of Targeted Next-generation Sequencing, TruSeq Custom Amplicon Assay for Molecular Pathology Diagnostics on Formalin-fixed and Paraffin-embedded Samples. AB - The implementation of targeted therapies revolutionized oncology. As the number of new oncogenic driver mutations, which provide molecular targets for prediction of effective and selective therapies, is increasing, the implementation of fast and reliable methods by molecular pathology labs is very important. Here we report our results with TruSeq Custom Amplicon assay performed on formalin-fixed and paraffin-embedded material. The oligo capture probes targeted the hotspot regions of 10 well-known oncogenes linked to clinical diagnosis and treatment of lung and colorectal adenocarcinomas, melanomas, and gastrointestinal stromal tumors. Fifteen previously genotyped formalin-fixed and paraffin-embedded DNA samples from different tumor types were selected for massively parallel sequencing. A bioinformatics pipeline was developed to identify high-quality variants and remove sequence artifacts. With the exception of 1 sample, which was of lower quality than the others, relevant mutations corresponding to tumor types could be reliable detected by the developed bioinformatical pipeline. This study indicates that the application of TruSeq Custom Amplicon assay is a promising tool in molecular pathology diagnostics, but it is important to standardize sample processing (including fixation, isolation procedure, sample selection based on quality assessment, and rigorous variant calling) to achieve the highest success rate and avoid false results. PMID- 26808134 TI - Napsin A Expression in Anaplastic Lymphoma Kinase-positive Diffuse Large B-Cell Lymphoma: A Diagnostic Pitfall. AB - BACKGROUND: Napsin A is frequently used to classify a tumor of unknown origin as lung primary. Recent studies have shown that Napsin A positivity occurs in adenocarcinomas of nonpulmonary origin such as renal cell carcinomas, endometrial carcinomas, and clear cell carcinomas of ovary. Nonspecific reactivity has been reported with polyclonal Napsin A antibody. On the basis of an index case of anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma (ALK-DLBCL) expressing Napsin A, which was misdiagnosed as poorly differentiated carcinoma of pulmonary origin, we studied Napsin A expression in our archived cases of ALK DLBCL. MATERIALS AND METHODS: A total of 3 cases of ALK-DLBCL were studied for Napsin A immunohistochemistry along with typical immunophenotypic profile of these cases. Archived paraffin-embedded tissue blocks and cytology aspiration smears were used for morphologic interpretation and immunohistochemistry. Rabbit monoclonal Napsin A antibody has been used. RESULTS AND CONCLUSIONS: All 3 cases were positive for Napsin A exhibiting strong cytoplasmic positivity. To the best of our knowledge, expression of monoclonal Napsin A in lymphomas has never been reported. ALK-DLBCL should be considered in the differential diagnosis when evaluating a Napsin A-positive tumor of poorly differentiated morphology and of unknown primary. As Napsin A has not been described in the lymphoid tissue development, the significance of Napsin A positivity in hematolymphoid neoplasms is unknown and warrants further investigation. PMID- 26808135 TI - Correlation of Classic and Molecular Cytogenetic Alterations in Soft-Tissue Sarcomas: Analysis of 46 Tumors With Emphasis on Adipocytic Tumors and Synovial Sarcoma. AB - INTRODUCTION: Sarcomas are heterogeneous, and their treatment and prognosis are driven by the morphologic subtype and the clinical stage. Classic cytogenetics and fluorescence in situ hybridization (FISH) analysis play an important role in their diagnostic work up. MATERIALS AND METHODS: Forty-six cases of soft-tissue sarcoma were reviewed that underwent karyotyping and simultaneous FISH analysis at initial diagnosis. They included 10 dedifferentiated liposarcomas, 10 myxoid liposarcomas, and 14 synovial sarcomas. Six tumors were investigated for EWSR1 rearrangement. Six high-grade miscellaneous sarcomas were also examined. RESULTS: The dedifferentiated liposarcoma had complex karyotypes and MDM2 amplification by FISH, and of these, 5 tumors with myxoid changes also had complex signals for DDIT3. All but 4 myxoid liposarcomas had complex karyotypes, in addition to the characteristic translocation. FISH analysis displayed DD1T3 rearrangement. All synovial sarcomas except 1 recurrence had a t(X;18) translocation by karyotyping and FISH. The EWSR1 rearrangement was present in all extraskeletal myxoid chondrosarcomas, angiomatoid fibrous histiocytoma, atypical Ewing sarcoma, and a clear-cell sarcoma, all of which had characteristic karyotypes. Seven high-grade sarcomas had no specific karyotype or rearrangements for DDIT3, SS18, and EWSR1 by FISH. CONCLUSIONS: There is good correlation between karyotyping and FISH. Complex FISH signals found in dedifferentiated liposarcomas may be related to an increased chromosome 12 copy number and ploidy. Karyotyping is an important baseline standard for the quality assurance of newly developed FISH probes. It also provides a global view of chromosomal changes and the opportunity to investigate the role of other genetic alterations and potential therapeutic targets. PMID- 26808136 TI - Is Long-Term Low-Dose Aspirin Therapy Associated with Renal Dysfunction in Patients with Type 2 Diabetes? JPAD2 Cohort Study. AB - BACKGROUND: Low-dose aspirin is widely recommended for patients at high risk for cardiovascular disease (CVD); however, it remains uncertain whether long-term treatment adversely affects renal function in patients with diabetes. We investigated whether long-term low-dose aspirin affects renal dysfunction in patients with diabetes. METHODS: We conducted a randomized controlled trial (RCT), the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, to evaluate low-dose aspirin as primary prevention for CVD in patients with type 2 diabetes. We followed the patients with negative urine dipstick albumin of the JPAD trial in a cohort study after the RCT period was completed. Patients were randomly allocated to receive aspirin (81 mg or 100 mg daily, aspirin group) or no aspirin (no aspirin group). After the RCT, the treating physician decided whether to administer aspirin. We evaluated the incidence of positive urine dipstick albumin and annual changes in estimated glomerular filtration rate (eGFR). RESULTS: Positive urine dipstick albumin developed in 297 patients in the aspirin group (n = 1,075) and 270 patients in the no aspirin group (n = 1,098) during follow-up (median, 8.5 years). Intention to-treat analysis showed low-dose aspirin did not increase the incidence of positive urine dipstick albumin (hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.995-1.38). On-treatment analysis yielded similar results (HR, 1.08; 95% CI, 0.92-1.28). Multivariable analysis showed the incidence of positive urine dipstick albumin was higher among the elderly and those with elevated serum creatinine, high hemoglobin A1c, or high blood pressure; however, low-dose aspirin did not increase the risk of positive urine dipstick albumin. There were no significant differences in annual changes in eGFR between the groups (aspirin, -0.8 +/- 2.9; no aspirin, -0.9 +/- 2.5 ml/min/1.73 m(2)/year). CONCLUSION: Long term low-dose aspirin does not affect eGFR and positive urine dipstick albumin in patients with type 2 diabetes. PMID- 26808137 TI - Comparative Cost Analysis of Sequential, Adaptive, Behavioral, Pharmacological, and Combined Treatments for Childhood ADHD. AB - We conducted a cost analysis of the behavioral, pharmacological, and combined interventions employed in a sequential, multiple assignment, randomized, and adaptive trial investigating the sequencing and enhancement of treatment for children with attention deficit hyperactivity disorder (ADHD; Pelham et al., 201X; N = 146, 76% male, 80% Caucasian). The quantity of resources expended on each child's treatment was determined from records that listed the type, date, location, persons present, and duration of all services provided. The inputs considered were the amount of physician time, clinician time, paraprofessional time, teacher time, parent time, medication, and gasoline. Quantities of these inputs were converted into costs in 2013 USD using national wage estimates from the Bureau of Labor Statistics, the prices of 30-day supplies of prescription drugs from the national Express Scripts service, and mean fuel prices from the Energy Information Administration. Beginning treatment with a low-dose/intensity regimen of behavior modification (large-group parent training) was less costly for a school year of treatment ($961) than beginning treatment with a low dose of stimulant medication ($1,669), regardless of whether the initial treatment was intensified with a higher "dose" or if the other modality was added. Outcome data from the parent study (Pelham et al., 201X) found equivalent or superior outcomes for treatments beginning with low-intensity behavior modification compared to intervention beginning with medication. Combined with the present analyses, these findings suggest that initiating treatment with behavior modification rather than medication is the more cost-effective option for children with ADHD. PMID- 26808138 TI - Biomarkers of gut barrier failure in the ICU. AB - PURPOSE OF REVIEW: Gut barrier failure is associated with bacterial translocation, systemic inflammation, and is presumed to be associated with the development of multiple organ dysfunction syndrome. As the gut barrier function is carried out by a monolayer of enterocytes, a minimum requirement is the integrity of the enterocytes, and controlled paracellular permeability between adjacent enterocytes. Many factors can cause critically ill patients to lose gut barrier function by a mechanism of enterocyte damage; for example, small bowel ischemia or hypoxia, sepsis, systemic inflammatory response syndrome, or absence of enteral feeding. RECENT FINDINGS: Two enterocyte biomarkers may help the intensivist to identify enterocyte damage and dysfunction, namely plasma citrulline, a biomarker of functional enterocyte mass, and plasma or urinary intestinal fatty acid-binding protein, a marker of enterocyte damage. This review focuses on results obtained with these biomarkers in the context of critical care, in particular: prevalence of enterocyte biomarker abnormalities; mechanisms associated with enterocyte damage and dysfunction; link with systemic inflammation, bacterial translocation, and clinical intestinal dysfunction; prognostic value of enterocyte biomarkers. Lastly, we also review the limits of these biomarkers. SUMMARY: Enterocyte biomarkers may help the intensivist to identify patients presenting with intestinal damage, and who are at risk of bacterial translocation and systemic inflammatory response syndrome, as well as those with decreased enterocyte function, at risk of malabsorption. Enterocyte biomarkers should be interpreted with caution in the critically ill and should be interpreted within the overall clinical context of the patient. PMID- 26808139 TI - Development of broad virus resistance in non-transgenic cucumber using CRISPR/Cas9 technology. AB - Genome editing in plants has been boosted tremendously by the development of CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats) technology. This powerful tool allows substantial improvement in plant traits in addition to those provided by classical breeding. Here, we demonstrate the development of virus resistance in cucumber (Cucumis sativus L.) using Cas9/subgenomic RNA (sgRNA) technology to disrupt the function of the recessive eIF4E (eukaryotic translation initiation factor 4E) gene. Cas9/sgRNA constructs were targeted to the N' and C' termini of the eIF4E gene. Small deletions and single nucleotide polymorphisms (SNPs) were observed in the eIF4E gene targeted sites of transformed T1 generation cucumber plants, but not in putative off target sites. Non-transgenic heterozygous eif4e mutant plants were selected for the production of non-transgenic homozygous T3 generation plants. Homozygous T3 progeny following Cas9/sgRNA that had been targeted to both eif4e sites exhibited immunity to Cucumber vein yellowing virus (Ipomovirus) infection and resistance to the potyviruses Zucchini yellow mosaic virus and Papaya ring spot mosaic virus W. In contrast, heterozygous mutant and non-mutant plants were highly susceptible to these viruses. For the first time, virus resistance has been developed in cucumber, non-transgenically, not visibly affecting plant development and without long-term backcrossing, via a new technology that can be expected to be applicable to a wide range of crop plants. PMID- 26808140 TI - Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof of-Concept Study. AB - BACKGROUND AND AIMS: Early detection of fibrosis is important in identifying individuals at risk for advanced liver disease in non-alcoholic fatty liver disease (NAFLD). We tested whether second-harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) microscopy, detecting fibrillar collagen and fat in a label-free manner, might allow automated and sensitive quantification of early fibrosis in NAFLD. METHODS: We analyzed 32 surgical biopsies from patients covering histological fibrosis stages 0-4, using multimodal label-free microscopy. Native samples were visualized by SHG and CARS imaging for detecting fibrillar collagen and fat. Furthermore, we developed a method for quantitative assessment of early fibrosis using automated analysis of SHG signals. RESULTS: We found that the SHG mean signal intensity correlated well with fibrosis stage and the mean CARS signal intensity with liver fat. Little overlap in SHG signal intensities between fibrosis stages 0 and 1 was observed. A specific fibrillar SHG signal was detected in the liver parenchyma outside portal areas in all samples histologically classified as having no fibrosis. This signal correlated with immunohistochemical location of fibrillar collagens I and III. CONCLUSIONS: This study demonstrates that label-free SHG imaging detects fibrillar collagen deposition in NAFLD more sensitively than routine histological staging and enables observer-independent quantification of early fibrosis in NAFLD with continuous grading. PMID- 26808142 TI - The University of Rhode Island Change Assessment as Predictor of Treatment Outcome and Dropout in Outpatients with Obsessive-Compulsive Disorder Treated with Exposure and Response Prevention. PMID- 26808141 TI - Synaptic Vesicle Recycling Is Unaffected in the Ts65Dn Mouse Model of Down Syndrome. AB - Down syndrome (DS) is the most common genetic cause of intellectual disability, and arises from trisomy of human chromosome 21. Accumulating evidence from studies of both DS patient tissue and mouse models has suggested that synaptic dysfunction is a key factor in the disorder. The presence of several genes within the DS trisomy that are either directly or indirectly linked to synaptic vesicle (SV) endocytosis suggested that presynaptic dysfunction could underlie some of these synaptic defects. Therefore we determined whether SV recycling was altered in neurons from the Ts65Dn mouse, the best characterised model of DS to date. We found that SV exocytosis, the size of the SV recycling pool, clathrin-mediated endocytosis, activity-dependent bulk endocytosis and SV generation from bulk endosomes were all unaffected by the presence of the Ts65Dn trisomy. These results were obtained using battery of complementary assays employing genetically encoded fluorescent reporters of SV cargo trafficking, and fluorescent and morphological assays of fluid-phase uptake in primary neuronal culture. The absence of presynaptic dysfunction in central nerve terminals of the Ts65Dn mouse suggests that future research should focus on the established alterations in excitatory / inhibitory balance as a potential route for future pharmacotherapy. PMID- 26808143 TI - Long-term patterns of chronic complaints of the arms, neck, and shoulders and their determinants--the Doetinchem Cohort Study. AB - Complaints of the arms, neck, and shoulders (CANS) represent a major public health problem but the long-term course is largely unknown. Our objective was to explore the 15-year course of chronic CANS and its determinants in a population based cohort. During 1993 to 2012, 3050 men and women aged 26 to 65 years at baseline were measured every 5 years, up to 4 times. Complaints of the arms, neck, and shoulders and sociodemographic, lifestyle, mental health, and physical load determinants were obtained by self-reported questionnaires and physical examinations. Information on chronic CANS was used to create patterns of the 15 year course: persistence, recovery, variable, no CANS, and the development of CANS. Only 47% were free of chronic CANS throughout the total 15-year period. The prevalence of other patterns was development (18.3%), persistence (8.5%), recovery (7.5%), and variable (18.7%). In multivariable logistic regression analyses, female gender, age 46 to 55 years, being not employed, former smoking, physical inactivity, an episode of CANS during the past 12 months, and high physical load in daily life (eg, often adopting awkward postures, frequent lifting, carrying, pushing, or pulling) were associated with the development of chronic CANS. Female gender, age 36 to 45 years, being not employed, and awkward postures in daily life were associated with persistent CANS. We conclude that chronic CANS represent a dynamic condition and affect the majority of the general population at least once in 15 years. Determinants associated with chronic CANS, especially physical load in daily life, can be used to develop preventive interventions and give guidance to treatment. PMID- 26808144 TI - Distinct TRPV1- and TRPA1-based mechanisms underlying enhancement of oral ulcerative mucositis-induced pain by 5-fluorouracil. AB - In many patients with cancer, chemotherapy-induced severe oral ulcerative mucositis causes intractable pain, leading to delays and interruptions in therapy. However, the pain mechanism in oral ulcerative mucositis after chemotherapy has not been extensively studied. In this study, we investigated spontaneous pain and mechanical allodynia in a preclinical model of oral ulcerative mucositis after systemic administration of the chemotherapy drug 5 fluorouracil, using our proprietary pain assay system for conscious rats. 5 Fluorouracil caused leukopenia but did not induce pain-related behaviors. After 5 fluorouracil administration, oral ulcers were developed with topical acetic acid treatment. Compared with saline-treated rats, 5-fluorouracil-exposed rats showed more severe mucositis with excessive bacterial loading due to a lack of leukocyte infiltration, as well as enhancements of spontaneous pain and mechanical allodynia. Antibacterial drugs, the lipid A inhibitor polymyxin B and the TRPV1/TRPA1 channel pore-passing anesthetic QX-314, suppressed both the spontaneous pain and the mechanical allodynia. The cyclooxygenase inhibitor indomethacin and the TRPV1 antagonist SB-366791 inhibited the spontaneous pain, but not the mechanical allodynia. In contrast, the TRPA1 antagonist HC-030031 and the N-formylmethionine receptor FPR1 antagonist Boc MLF primarily suppressed the mechanical allodynia. These results suggest that 5-fluorouracil-associated leukopenia allows excessive oral bacterial infection in the oral ulcerative region, resulting in the enhancement of spontaneous pain through continuous TRPV1 activation and cyclooxygenase pathway, and mechanical allodynia through mechanical sensitization of TRPA1 caused by neuronal effects of bacterial toxins. These distinct pain mechanisms explain the difficulties encountered with general treatments for oral ulcerative mucositis-induced pain in patients with cancer and suggest more effective approaches. PMID- 26808145 TI - iPeer2Peer program: a pilot feasibility study in adolescents with chronic pain. AB - Adolescents with chronic pain are often socially isolated, having never met others with chronic pain, and often feel misunderstood by healthy peers. Adolescence is a sensitive period for developing one's sense of self and autonomy, which often occurs in the context of peer relationships. This developmental process is disrupted in adolescents when their chronic pain interferes with their social interactions. Peer mentoring is proposed as a developmentally timely intervention. The aim of this study is to develop and test the feasibility, acceptability, and impact of the iPeer2Peer program. The iPeer2Peer program is a tailored peer mentorship program that provides modeling and reinforcement by peers (trained young adults with chronic pain aged 18-25 years who have learned to successfully manage their pain). This program aimed to enhance self-management of chronic pain in adolescents through 10 Skype video calls over the course of 8 weeks. A pilot randomized controlled trial design using waitlist controls was used in an adolescent chronic pain sample. Twenty eight adolescents aged 14.8 +/- 1.6 years (93% female) completed the trial (intervention: n = 12; control n = 16). Three adolescents completed the intervention after completing their participation in the control arm. The iPeer2Peer program was feasible and acceptable, provided the adolescents were given more time to complete all 10 calls. When compared with controls, adolescents who completed the iPeer2Peer program had significant improvement in self-management skills and their coping efforts were more successful. The iPeer2Peer program is a promising peer mentoring intervention that complements standard care for adolescents with chronic pain. PMID- 26808146 TI - Pressure-induced referred pain is expanded by persistent soreness. AB - Several chronic pain conditions are accompanied with enlarged referred pain areas. This study investigated a novel method for assessing referred pain. In 20 healthy subjects, pressure pain thresholds (PPTs) were recorded and pressure stimuli (120% PPT) were applied bilaterally for 5 and 60 seconds at the infraspinatus muscle to induce local and referred pain. Moreover, PPTs were measured bilaterally at the shoulder, neck, and leg before, during, and after hypertonic saline-induced referred pain in the dominant infraspinatus muscle. The pressure and saline-induced pain areas were assessed on drawings. Subsequently, delayed onset muscle soreness was induced using eccentric exercise of the dominant infraspinatus muscle. The day-1 assessments were repeated the following day (day 2). Suprathreshold pressure stimulations and saline injections into the infraspinatus muscle caused referred pain to the frontal aspect of the shoulder/arm in all subjects. The 60-second pressure stimulation caused larger referred pain areas compared with the 5-second stimulation (P < 0.01). Compared with pressure stimulation, the saline-induced referred pain area was larger (P < 0.02). After saline-induced pain, the PPTs at the infraspinatus and supraspinatus muscles were reduced (P < 0.05), and the 5-second pressure-induced referred pain area was larger than baseline. Pressure pain thresholds at the infraspinatus and supraspinatus muscles were reduced at day 2 in the delayed onset muscle soreness side (P < 0.05). Compared with day 1, larger pressure and saline-induced referred pain areas were observed on day 2 (P < 0.05). Referred pain to the shoulder/arm was consistently induced and enlarged after 1 day of muscle soreness, indicating that the referred pain area may be a sensitive biomarker for sensitization of the pain system. PMID- 26808147 TI - Palladium(II), Ruthenium(II), and Ruthenium(III) Complexes of 23 Thiaazuliporphyrin: The Case of Coordination-Induced Contraction. AB - 5,10,15,20-Tetraaryl-23-thiaazuliporphyrin (SAz) was synthesized starting from nonfunctionalized azulene using a "1 + 3" method to be applied as a monoanionic macrocyclic ligand that provides a peculiar [CNSN] coordination cavity. An insertion of palladium(II) afforded the cationic [Pd(II)(SAz)](+), which readily undergoes the seven-membered ring contraction to form palladium(II) 23 thiabenzocarbaporphyrin [Pd(SBzC)] providing the first example of metal azuliporphyrinoid contraction. A reaction of SAz and a ruthenium source ([RuCl2(CO)3]2, [RuCl2(p-cymene)]2, or [RuCl2(cod)]) yielded ruthenium(II) 23 thiaazuliporphyrin [Ru(II)(SAz)Cl(CO)]. As shown by X-ray crystallography the thiophene ring in [Ru(SAz)Cl(CO)] is sharply tilted out of the plane of the two pyrrole nitrogen and carbon atoms being bound to the ruthenium through the pyramidal sulfur in the eta(1) fashion. In solution, as demonstrated by variable temperature (1)H NMR investigations, [Ru(SAz)Cl(CO)] exists as an equilibrium mixture of two isomers that are differentiated by the direction of thiophene folding (toward or outward of the axial chloride ligand). Apart of [Ru(II)(SAz)Cl(CO)], ruthenium(III) 23-thiaazuliporphyrin [Ru(III)(SAz)Cl2] was obtained when [RuCl2(p-cymene)]2 or [RuCl2(cod)]n were used for insertion. The most characteristic (1)H NMR features of paramagnetic [Ru(SAz)Cl2] are negative isotropic shifts of resonances assigned to meso-aryl, azulene, and pyrrolic hydrogen atoms. The analysis of contact shifts and the parallel density functional theory calculations of spin density distribution documented that in [Ru(SAz)Cl2] the metal ion acquires the d(xy)(2)(d(xz)d(yz))(3) ground electronic state. This C(s) symmetry complex has singly occupied d(xz) or d(yz) orbitals that are symmetrically unequivalent. The resulting two different spin density distributions, when merged, reflect the spectroscopic image with the very specific pi-spin delocalization, also including the azulene moiety. PMID- 26808148 TI - Learning to Produce Syllabic Speech Sounds via Reward-Modulated Neural Plasticity. AB - At around 7 months of age, human infants begin to reliably produce well-formed syllables containing both consonants and vowels, a behavior called canonical babbling. Over subsequent months, the frequency of canonical babbling continues to increase. How the infant's nervous system supports the acquisition of this ability is unknown. Here we present a computational model that combines a spiking neural network, reinforcement-modulated spike-timing-dependent plasticity, and a human-like vocal tract to simulate the acquisition of canonical babbling. Like human infants, the model's frequency of canonical babbling gradually increases. The model is rewarded when it produces a sound that is more auditorily salient than sounds it has previously produced. This is consistent with data from human infants indicating that contingent adult responses shape infant behavior and with data from deaf and tracheostomized infants indicating that hearing, including hearing one's own vocalizations, is critical for canonical babbling development. Reward receipt increases the level of dopamine in the neural network. The neural network contains a reservoir with recurrent connections and two motor neuron groups, one agonist and one antagonist, which control the masseter and orbicularis oris muscles, promoting or inhibiting mouth closure. The model learns to increase the number of salient, syllabic sounds it produces by adjusting the base level of muscle activation and increasing their range of activity. Our results support the possibility that through dopamine-modulated spike-timing dependent plasticity, the motor cortex learns to harness its natural oscillations in activity in order to produce syllabic sounds. It thus suggests that learning to produce rhythmic mouth movements for speech production may be supported by general cortical learning mechanisms. The model makes several testable predictions and has implications for our understanding not only of how syllabic vocalizations develop in infancy but also for our understanding of how they may have evolved. PMID- 26808149 TI - Sensitivity and Specificity of Cardiac Tissue Discrimination Using Fiber-Optics Confocal Microscopy. AB - Disturbances of the cardiac conduction system constitute a major risk after surgical repair of complex cases of congenital heart disease. Intraoperative identification of the conduction system may reduce the incidence of these disturbances. We previously developed an approach to identify cardiac tissue types using fiber-optics confocal microscopy and extracellular fluorophores. Here, we applied this approach to investigate sensitivity and specificity of human and automated classification in discriminating images of atrial working myocardium and specialized tissue of the conduction system. Two-dimensional image sequences from atrial working myocardium and nodal tissue of isolated perfused rodent hearts were acquired using a fiber-optics confocal microscope (Leica FCM1000). We compared two methods for local application of extracellular fluorophores: topical via pipette and with a dye carrier. Eight blinded examiners evaluated 162 randomly selected images of atrial working myocardium (n = 81) and nodal tissue (n = 81). In addition, we evaluated the images using automated classification. Blinded examiners achieved a sensitivity and specificity of 99.2 +/- 0.3% and 98.0 +/- 0.7%, respectively, with the dye carrier method of dye application. Sensitivity and specificity was similar for dye application via a pipette (99.2 +/- 0.3% and 94.0 +/- 2.4%, respectively). Sensitivity and specificity for automated methods of tissue discrimination were similarly high. Human and automated classification achieved high sensitivity and specificity in discriminating atrial working myocardium and nodal tissue. We suggest that our findings facilitate clinical translation of fiber-optics confocal microscopy as an intraoperative imaging modality to reduce the incidence of conduction disturbances during surgical correction of congenital heart disease. PMID- 26808150 TI - Transcriptome Sequencing in Response to Salicylic Acid in Salvia miltiorrhiza. AB - Salvia miltiorrhiza is a traditional Chinese herbal medicine, whose quality and yield are often affected by diseases and environmental stresses during its growing season. Salicylic acid (SA) plays a significant role in plants responding to biotic and abiotic stresses, but the involved regulatory factors and their signaling mechanisms are largely unknown. In order to identify the genes involved in SA signaling, the RNA sequencing (RNA-seq) strategy was employed to evaluate the transcriptional profiles in S. miltiorrhiza cell cultures. A total of 50,778 unigenes were assembled, in which 5,316 unigenes were differentially expressed among 0-, 2-, and 8-h SA induction. The up-regulated genes were mainly involved in stimulus response and multi-organism process. A core set of candidate novel genes coding SA signaling component proteins was identified. Many transcription factors (e.g., WRKY, bHLH and GRAS) and genes involved in hormone signal transduction were differentially expressed in response to SA induction. Detailed analysis revealed that genes associated with defense signaling, such as antioxidant system genes, cytochrome P450s and ATP-binding cassette transporters, were significantly overexpressed, which can be used as genetic tools to investigate disease resistance. Our transcriptome analysis will help understand SA signaling and its mechanism of defense systems in S. miltiorrhiza. PMID- 26808151 TI - Understanding Statin Non-Adherence: Knowing Which Perceptions and Experiences Matter to Different Patients. AB - BACKGROUND: Non-adherence to statins is substantial and is associated with numerous perceptions and experiences. However, time limits in clinical practice constrain in depth explorations of these perceptions and experiences. OBJECTIVES: To propose and examine a strategy aimed at an efficient assessment of a wide array of perceptions and experiences regarding the efficacy, side effects, and practical problems of statins. Furthermore, to assess associations between this wide array of experiences and perceptions and non-adherence and to examine whether patients' 'perceived self-efficacy' moderated these associations. METHODS: Patients were recruited through community pharmacies. A wide array of specific patient perceptions and experiences was efficiently assessed using the electronic Tailored Medicine Inventory that allows people to skip irrelevant questions. Adherence was measured through self-report and pharmacy refill data. RESULTS: Of the two-hundred twenty-nine patients who participated (mean age 63.9, standard deviation 10.2), 40%-70% doubted the necessity of or lacked knowledge about the efficacy of statins, 20%-35% of the patients were worried about joint and muscle side effects or had experienced these, and 23% had encountered practical problems regarding information about statins, intake of tablets, the package, or the blister. Experiencing more practical problems was associated with increased unintentional non-adherence (Odds ratio 1.54, 95%CI:1.13-2.10, P < 0.01), whereas worrying about side effects was associated with increased intentional non-adherence (Odds ratio 1.90, 95%CI:1.17-3.08, P < 0.01). Higher 'perceived self-efficacy' did not moderate these associations. CONCLUSIONS: Insight into patients' specific barriers with regard to appropriate statin use may reveal personal reasons for being non-adherent. The Tailored Medicine Inventory is a promising tool to devise individualized intervention strategies aimed at improving adherence by the clinician-patient alliance. PMID- 26808153 TI - Correction: Methionine Mistranslation Bypasses the Restraint of the Genetic Code to Generate Mutant Proteins with Distinct Activities. AB - [This corrects the article DOI: 10.1371/journal.pgen.1005745.]. PMID- 26808152 TI - Network-Based Meta-Analyses of Associations of Multiple Gene Expression Profiles with Bone Mineral Density Variations in Women. AB - BACKGROUND: Existing microarray studies of bone mineral density (BMD) have been critical for understanding the pathophysiology of osteoporosis, and have identified a number of candidate genes. However, these studies were limited by their relatively small sample sizes and were usually analyzed individually. Here, we propose a novel network-based meta-analysis approach that combines data across six microarray studies to identify functional modules from human protein-protein interaction (PPI) data, and highlight several differentially expressed genes (DEGs) and a functional module that may play an important role in BMD regulation in women. METHODS: Expression profiling studies were identified by searching PubMed, Gene Expression Omnibus (GEO) and ArrayExpress. Two meta-analysis methods were applied across different gene expression profiling studies. The first, a nonparametric Fisher's method, combined p-values from individual experiments to identify genes with large effect sizes. The second method combined effect sizes from individual datasets into a meta-effect size to gain a higher precision of effect size estimation across all datasets. Genes with Q test's p-values < 0.05 or I(2) values > 50% were assessed by a random effects model and the remainder by a fixed effects model. Using Fisher's combined p-values, functional modules were identified through an integrated analysis of microarray data in the context of large protein-protein interaction (PPI) networks. Two previously published meta analysis studies of genome-wide association (GWA) datasets were used to determine whether these module genes were genetically associated with BMD. Pathway enrichment analysis was performed with a hypergeometric test. RESULTS: Six gene expression datasets were identified, which included a total of 249 (129 high BMD and 120 low BMD) female subjects. Using a network-based meta-analysis, a consensus module containing 58 genes (nodes) and 83 edges was detected. Pathway enrichment analysis of the 58 module genes revealed that these genes were enriched in several important KEGG pathways including Osteoclast differentiation, B cell receptor signaling pathway, MAPK signaling pathway, Chemokine signaling pathway and Insulin signaling pathway. The importance of module genes was replicated by demonstrating that most module genes were genetically associated with BMD in the GWAS data sets. Meta-analyses were performed at the individual gene level by combining p-values and effect sizes. Five candidate genes (ESR1, MAP3K3, PYGM, RAC1 and SYK) were identified based on gene expression meta analysis, and their associations with BMD were also replicated by two BMD meta analysis studies. CONCLUSIONS: In summary, our network-based meta-analysis not only identified important differentially expressed genes but also discovered biologically meaningful functional modules for BMD determination. Our study may provide novel therapeutic targets for osteoporosis in women. PMID- 26808154 TI - A New Data Analysis System to Quantify Associations between Biochemical Parameters of Chronic Kidney Disease-Mineral Bone Disease. AB - BACKGROUND: In hemodialysis patients, deviations from KDIGO recommended values of individual parameters, phosphate, calcium or parathyroid hormone (PTH), are associated with increased mortality. However, it is widely accepted that these parameters are not regulated independently of each other and that therapy aimed to correct one parameter often modifies the others. The aim of the present study is to quantify the degree of association between parameters of chronic kidney disease and mineral bone disease (CKD-MBD). METHODS: Data was extracted from a cohort of 1758 adult HD patients between January 2000 and June 2013 obtaining a total of 46.141 records (10 year follow-up). We used an advanced data analysis system called Random Forest (RF) which is based on self-learning procedure with similar axioms to those utilized for the development of artificial intelligence. This new approach is particularly useful when the variables analyzed are closely dependent to each other. RESULTS: The analysis revealed a strong association between PTH and phosphate that was superior to that of PTH and Calcium. The classical linear regression analysis between PTH and phosphate shows a correlation coefficient is 0.27, p<0.001, the possibility to predict PTH changes from phosphate modification is marginal. Alternatively, RF assumes that changes in phosphate will cause modifications in other associated variables (calcium and others) that may also affect PTH values. Using RF the correlation coefficient between changes in serum PTH and phosphate is 0.77, p<0.001; thus, the power of prediction is markedly increased. The effect of therapy on biochemical variables was also analyzed using this RF. CONCLUSION: Our results suggest that the analysis of the complex interactions between mineral metabolism parameters in CKD MBD may demand a more advanced data analysis system such as RF. PMID- 26808157 TI - Relationship between enamel fluorosis severity and fluoride content. AB - OBJECTIVES: Enamel fluorosis is a hypomineralization caused by chronic exposure to high levels of fluoride during tooth development. Previous research on the relationship between enamel fluoride content and fluorosis severity has been equivocal. The current study aimed at comparing visually and histologically assessed fluorosis severity with enamel fluoride content. METHODS: Extracted teeth (n=112) were visually examined using the Thylstrup and Fejerskov Index for fluorosis. Eruption status of each tooth was noted. Teeth were cut into 100 MUm slices to assess histological changes with polarized light microscopy. Teeth were categorized as sound, mild, moderate, or severe fluorosis, visually and histologically. They were cut into squares (2 * 2 mm) for the determination of fluoride content (microbiopsy) at depths of 30, 60 and 90 MUm from the external surface. RESULTS: Erupted teeth with severe fluorosis had significantly greater mean fluoride content at 30, 60 and 90 MUm than sound teeth. Unerupted teeth with mild, moderate and severe fluorosis had significantly greater mean fluoride content than sound teeth at 30 MUm; unerupted teeth with mild and severe fluorosis had significantly greater mean fluoride content than sound teeth at 60 MUm, while only unerupted teeth severe fluorosis had significantly greater mean fluoride content than sound teeth at 90 MUm. CONCLUSIONS: Both erupted and unerupted severely fluorosed teeth presented higher mean enamel fluoride content than sound teeth. CLINICAL SIGNIFICANCE: Data on fluoride content in enamel will further our understanding of its biological characteristics which play a role in the management of hard tissue diseases and conditions. PMID- 26808155 TI - The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort. AB - BACKGROUND: In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). METHODS AND FINDINGS: We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for >= 15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). CONCLUSIONS: Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors. PMID- 26808156 TI - Impact of Azithromycin on the Quorum Sensing-Controlled Proteome of Pseudomonas aeruginosa. AB - The macrolide antibiotic, azithromycin (AZM), has been reported to improve the clinical outcome of cystic fibrosis patients, many of whom are chronically infected with Pseudomonas aeruginosa. However, the highest clinically-achievable concentrations of this drug are well-below the minimum inhibitory concentration for P. aeruginosa, raising the question of why AZM exhibits therapeutic activity. One possibility that has been raised by earlier studies is that AZM inhibits quorum sensing (QS) by P. aeruginosa. To explicitly test this hypothesis the changes brought about by AZM treatment need to be compared with those associated with specific QS mutants grown alongside in the same growth medium, but this has not been done. In this work, we used quantitative 2D-difference gel electrophoresis and 1H-NMR spectroscopy footprint analysis to examine whether a range of clinically-relevant AZM concentrations elicited proteomic and metabolomic changes in wild-type cultures that were similar to those seen in cultures of defined QS mutants. Consistent with earlier reports, over half of the AZM-induced spot changes on the 2D gels were found to affect QS-regulated proteins. However, AZM modulated very few protein spots overall (compared with QS) and collectively, these modulated proteins comprised only a small fraction (12-13%) of the global QS regulon. We conclude that AZM perturbs a sub-regulon of the QS system but does not block QS per se. Reinforcing this notion, we further show that AZM is capable of attenuating virulence factor production in another Gram-negative species that secretes copious quantities of exoenzymes (Serratia marcescens), even in the absence of a functional QS system. PMID- 26808158 TI - Effects of water-aging on self-healing dental composite containing microcapsules. AB - OBJECTIVES: The objectives of this study were to develop a self-healing dental composite containing poly(urea-formaldehyde) (PUF) shells with triethylene glycol dimethacrylate (TEGDMA) and N,N-dihydroxyethyl-p-toluidine (DHEPT) as healing liquid, and to investigate the mechanical properties of the composite and its self-healing efficacy after water-aging for 6 months. METHODS: PUF microspheres were synthesized encapsulating a TEGDMA-DHEPT healing liquid. Composite containing 30% of a resin matrix and 70% of glass fillers by mass was incorporated with 0%, 2.5%, 5%, 7.5% and 10% of microcapsules. A flexural test was used to measure flexural strength and elastic modulus. A single edge V notched beam method was used to measure fracture toughness (KIC) and self-healing efficacy. Specimens were water-aged at 37 degrees C for 1 day to 6 months and then tested for self-healing. Fractured specimens were healed while being immersed in water to examine self-healing efficacy, in comparison with that in air. RESULTS: Incorporation of up to 7.5% of microcapsules into the resin composite achieved effective self-healing, without adverse effects on the virgin mechanical properties of the composite (p>0.1). An excellent self-healing efficacy of 64-77% recovery was obtained (mean+/-sd; n=6). Six months of water aging did not decrease the self-healing efficacy compared to 1 day (p>0.1). Exposure to water did not decrease the healing efficacy, compared to that healed in air (p>0.1). CONCLUSIONS: A composite was developed with excellent self healing efficacy even while being immersed in water. The self-healing efficacy did not decrease with increasing water-aging time for 6 months. CLINICAL SIGNIFICANCE: The novel self-healing composite may be promising for dental applications to heal cracks, resist fracture, and increase the durability and longevity. PMID- 26808159 TI - The effect of air-abrasion on the susceptibility of sound enamel to acid challenge. AB - OBJECTIVE: To evaluate the effect of air-abrasion using three abrasive powders, on the susceptibility of sound enamel to an acid challenge. METHODS: 40 human enamel samples were flattened, polished and assigned to 4 experimental groups (n=10); a: alumina air-abrasion, b: sodium bicarbonate air-abrasion, c: bioactive glass (BAG) air-abrasion and d: no surface treatment (control). White light confocal profilometry was used to measure the step height enamel loss of the abraded area within each sample at three stages; after sample preparation (baseline), after air-abrasion and finally after exposing the samples to pH cycling for 10 days. Data was analysed statistically using one-way ANOVA with Tukey's HSD post-hoc tests (p<0.05). Unique prismatic structures generated by abrasion and subsequent pH cycling were imaged using multiphoton excitation microscopy, exploiting strong autofluorescence properties of the enamel without labelling. Z-stacks of treated and equivalent control surfaces were used to generate non-destructively 3-dimensional surface profiles similar to those produced by scanning electron microscopy. RESULTS: There was no significant difference in the step height enamel loss after initial surface air-abrasion compared to the negative control group. However, a significant increase in the step height enamel loss was observed in the alumina air-abraded samples after pH cycling compared to the negative control (p<0.05). Sodium bicarbonate as well as BAG air-abrasion exhibited similar enamel surface loss to that detected in the negative control group (p>0.05). Surface profile examination revealed a deposition effect across sodium bicarbonate and BAG-abraded groups. CONCLUSION: This study demonstrates the importance of powder selection when using air abrasion technology in clinical dentistry. Pre-treating the enamel surface with alumina air-abrasion significantly increased its susceptibility to acid challenge. Therefore, when using alumina air-abrasion clinically, clinicians must be aware that abrading sound enamel excessively renders that surface more susceptible to the effects of acid erosion. BAG and sodium bicarbonate powders were less invasive when compared to the alumina powder, supporting their use for controlled surface stain removal from enamel where indicated clinically. PMID- 26808160 TI - Effects of Ageing on the Immune System: Infants to Elderly. AB - Physiological ageing is accompanied by decline in immune system function and immune alteration during ageing increases susceptibility to infections. We retrospectively analysed the data for complete blood count (CBC) and lymphocyte subsets from infant to elderly age groups to determine changes during ageing. Data from dual-platform flow cytometry and CBC were analysed to determine the percentage (%) and absolute cell counts (Abs) of peripheral blood lymphocyte subsets (CD3, CD4, CD8, CD19 and CD56+16+ cells) in infants (1 month to 1 year), children (1 year to 6 years), adolescents (12 years to 18 years), adults (21 years to 50) and elderly (70 years to 92 years). Differences in plasma cytokine levels in adults and elderly were also analysed using Randox system. Comparisons among age groups from infants through adults revealed progressive declines in the percentage of total lymphocytes and absolute numbers of T and B cells. The NK cells declined from infancy to adulthood but increased in elderly participants. The percentages of T cells increased with age from infant to adulthood and then declined. Pro-inflammatory cytokines, TNF-alpha and IL-6, were higher in elderly people compared to adults. The elderly group had significantly higher levels of monocyte chemoattractant protein-1 (MCP-1) and lower levels of epidermal growth factor (EGF) compared to adults. Our findings confirm and extend earlier reports on age-related changes in lymphocyte subpopulations and data generated from this study is useful for clinicians and researchers, patient management in various age groups for the interpretation of disease-related changes, as well as therapy dependent alterations. PMID- 26808161 TI - The role of glucuronidation in drug resistance. AB - The final therapeutic effect of a drug candidate, which is directed to a specific molecular target strongly depends on its absorption, distribution, metabolism and excretion (ADME). The disruption of at least one element of ADME may result in serious drug resistance. In this work we described the role of one element of this resistance: phase II metabolism with UDP-glucuronosyltransferases (UGTs). UGT function is the transformation of their substrates into more polar metabolites, which are better substrates for the ABC transporters, MDR1, MRP and BCRP, than the native drug. UGT-mediated drug resistance can be associated with (i) inherent overexpression of the enzyme, named intrinsic drug resistance or (ii) induced expression of the enzyme, named acquired drug resistance observed when enzyme expression is induced by the drug or other factors, as food-derived compounds. Very often this induction occurs via ligand binding receptors including AhR (aryl hydrocarbon receptor) PXR (pregnane X receptor), or other transcription factors. The effect of UGT dependent resistance is strengthened by coordinate action and also a coordinate regulation of the expression of UGTs and ABC transporters. This coupling of UGT and multidrug resistance proteins has been intensively studied, particularly in the case of antitumor treatment, when this resistance is "improved" by differences in UGT expression between tumor and healthy tissue. Multidrug resistance coordinated with glucuronidation has also been described here for drugs used in the management of epilepsy, psychiatric diseases, HIV infections, hypertension and hypercholesterolemia. Proposals to reverse UGT-mediated drug resistance should consider the endogenous functions of UGT. PMID- 26808162 TI - Aberrant lysine acetylation in tumorigenesis: Implications in the development of therapeutics. AB - The 'language' of covalent histone modifications translates environmental and cellular cues into gene expression. This vast array of post-translational modifications on histones are more than just covalent moieties added onto a protein, as they also form a platform on which crucial cellular signals are relayed. The reversible lysine acetylation has emerged as an important post translational modification of both histone and non-histone proteins, dictating numerous epigenetic programs within a cell. Thus, understanding the complex biology of lysine acetylation and its regulators is essential for the development of epigenetic therapeutics. In this review, we will attempt to address the complexities of lysine acetylation in the context of tumorigenesis, their role in cancer progression and emphasize on the modalities developed to target lysine acetyltransferases towards cancer treatment. PMID- 26808164 TI - Insight into SUCNR1 (GPR91) structure and function. AB - SUCNR1 (or GPR91) belongs to the family of G protein-coupled receptors (GPCR), which represents the largest group of membrane proteins in human genome. The majority of marketed drugs targets GPCRs, directly or indirectly. SUCNR1 has been classified as an orphan receptor until a landmark study paired it with succinate, a citric acid cycle intermediate. According to the current paradigm, succinate triggers SUCNR1 signaling pathways to indicate local stress that may affect cellular metabolism. SUCNR1 implication has been well documented in renin-induced hypertension, ischemia/reperfusion injury, inflammation and immune response, platelet aggregation and retinal angiogenesis. In addition, the SUCNR1-induced increase of blood pressure may contribute to diabetic nephropathy or cardiac hypertrophy. The understanding of SUCNR1 activation, signaling pathways and functions remains largely elusive, which calls for deeper investigations. SUCNR1 shows a high potential as an innovative drug target and is probably an important regulator of basic physiology. In order to achieve the full characterization of this receptor, more specific pharmacological tools such as small-molecules modulators will represent an important asset. In this review, we describe the structural features of SUCNR1, its current ligands and putative binding pocket. We give an exhaustive overview of the known and hypothetical signaling partners of the receptor in different in vitro and in vivo systems. The link between SUCNR1 intracellular pathways and its pathophysiological roles are also extensively discussed. PMID- 26808163 TI - Tumor cell vascular mimicry: Novel targeting opportunity in melanoma. AB - In 1999, the American Journal of Pathology published an article, entitled "Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry" by Maniotis and colleagues, which ignited a spirited debate for several years and earned the journal's distinction of a "citation classic" (Maniotis et al., 1999). Tumor cell vasculogenic mimicry (VM), also known as vascular mimicry, describes the plasticity of aggressive cancer cells forming de novo vascular networks and is associated with the malignant phenotype and poor clinical outcome. The tumor cells capable of VM share the commonality of a stem cell-like, transendothelial phenotype, which may be induced by hypoxia. Since its introduction as a novel paradigm for melanoma tumor perfusion, many studies have contributed new findings illuminating the underlying molecular pathways supporting VM in a variety of tumors, including carcinomas, sarcomas, glioblastomas, astrocytomas, and melanomas. Of special significance is the lack of effectiveness of angiogenesis inhibitors on tumor cell VM, suggesting a selective resistance by this phenotype to conventional therapy. Facilitating the functional plasticity of tumor cell VM are key proteins associated with vascular, stem cell, extracellular matrix, and hypoxia-related signaling pathways--each deserving serious consideration as potential therapeutic targets and diagnostic indicators of the aggressive, metastatic phenotype. This review highlights seminal findings pertinent to VM, including the effects of a novel, small molecular compound, CVM-1118, currently under clinical development to target VM, and illuminates important molecular pathways involved in the suppression of this plastic, aggressive phenotype, using melanoma as a model. PMID- 26808165 TI - Target identification of natural and traditional medicines with quantitative chemical proteomics approaches. AB - Natural and traditional medicines, being a great source of drugs and drug leads, have regained wide interests due to the limited success of high-throughput screening of compound libraries in the past few decades and the recent technology advancement. Many drugs/bioactive compounds exert their functions through interaction with their protein targets, with more and more drugs showing their ability to target multiple proteins, thus target identification has an important role in drug discovery and biomedical research fields. Identifying drug targets not only furthers the understanding of the mechanism of action (MOA) of a drug but also reveals its potential therapeutic applications and adverse side effects. Chemical proteomics makes use of affinity chromatography approaches coupled with mass spectrometry to systematically identify small molecule-protein interactions. Although traditional affinity-based chemical proteomics approaches have made great progress in the identification of cellular targets and elucidation of MOAs of many bioactive molecules, nonspecific binding remains a major issue which may reduce the accuracy of target identification and may hamper the drug development process. Recently, quantitative proteomics approaches, namely, metabolic labeling, chemical labeling, or label-free approaches, have been implemented in target identification to overcome such limitations. In this review, we will summarize and discuss the recent advances in the application of various quantitative chemical proteomics approaches for the identification of targets of natural and traditional medicines. PMID- 26808166 TI - Mechanisms behind efficacy of tumor necrosis factor inhibitors in inflammatory bowel diseases. AB - Biological treatment with tumor necrosis factor (TNF) inhibitors is successful in the management of inflammatory bowel disease (IBD). All TNF inhibitors antagonize the pro-inflammatory cytokine TNF-alpha but with varying efficacies in IBD. The variations in efficacy probably are caused by structural differences between the agents that affect their mechanisms of action and pharmacokinetic properties. Several mechanisms have been proposed, such as modulation of the expression of pro-inflammatory mediators and a reduction in the number of activated immune cells. However, it seems that clinical efficacy is the result of a number of different mechanisms and that binding of transmembrane TNF by TNF inhibitors. Knowledge of the mechanisms of action has been obtained mainly through the use of in vitro assays that may differ significantly from the situation in vivo. This review discusses the available data on TNF inhibitors in order to identify mechanisms of importance for their efficacy in IBD. Thus, a better understanding of the mechanistic basis for clinical efficacy can lead to a more rational use of TNF inhibitors in the management of IBD. PMID- 26808167 TI - beta3-Adrenoceptor agonists for overactive bladder syndrome: Role of translational pharmacology in a repositioning clinical drug development project. AB - beta3-Adrenoceptor agonists were originally considered as a promising drug class for the treatment of obesity and/or type 2 diabetes. When these development efforts failed, they were repositioned for the treatment of the overactive bladder syndrome. Based on the example of the beta3-adrenoceptor agonist mirabegron, but also taking into consideration evidence obtained with ritobegron and solabegron, we discuss challenges facing a translational pharmacology program accompanying clinical drug development for a first-in-class molecule. Challenges included generic ones such as ligand selectivity, species differences and drug target gene polymorphisms. Challenges that are more specific included changing concepts of the underlying pathophysiology of the target condition while clinical development was under way; moreover, a paucity of public domain tools for the study of the drug target and aspects of receptor agonists as drugs had to be addressed. Nonetheless, a successful first-in-class launch was accomplished. Looking back at this translational pharmacology program, we conclude that a specifically tailored and highly flexible approach is required. However, several of the lessons learned may also be applicable to translational pharmacology programs in other indications. PMID- 26808168 TI - Effects of payments for ecosystem services on wildlife habitat recovery. AB - Conflicts between local people's livelihoods and conservation have led to many unsuccessful conservation efforts and have stimulated debates on policies that might simultaneously promote sustainable management of protected areas and improve the living conditions of local people. Many government-sponsored payments for-ecosystem-services (PES) schemes have been implemented around the world. However, few empirical assessments of their effectiveness have been conducted, and even fewer assessments have directly measured their effects on ecosystem services. We conducted an empirical and spatially explicit assessment of the conservation effectiveness of one of the world's largest PES programs through the use of a long-term empirical data set, a satellite-based habitat model, and spatial autoregressive analyses on direct measures of change in an ecosystem service (i.e., the provision of wildlife species habitat). Giant panda (Ailuropoda melanoleuca) habitat improved in Wolong Nature Reserve of China after the implementation of the Natural Forest Conservation Program. The improvement was more pronounced in areas monitored by local residents than those monitored by the local government, but only when a higher payment was provided. Our results suggest that the effectiveness of a PES program depends on who receives the payment and on whether the payment provides sufficient incentives. As engagement of local residents has not been incorporated in many conservation strategies elsewhere in China or around the world, our results also suggest that using an incentive-based strategy as a complement to command-and-control, community- and norm-based strategies may help achieve greater conservation effectiveness and provide a potential solution for the park versus people conflict. PMID- 26808169 TI - Sonoelastography of Breast Lymphoma. AB - Breast lymphomas only account for approximately 0.15% of malignant breast carcinomas. Half of these are primary lymphomas, and the other half are metastatic to the breast. Ultrasound elastography has been proven to aid in the diagnosis of breast lesions as malignant or benign, with malignancy appearing stiffer compared with normal breast tissue. However, in this study, we review the findings of breast lymphoma on strain and shear wave ultrasonography. Lymphoma appears drastically different on sonoelastography than primary breast cancers, and it could easily be interpreted as benign. Therefore, the unique imaging findings in addition to the patient's clinical history are important in differentiating lymphoma of the breast from other possible diagnoses. PMID- 26808170 TI - Bioeffects of Diagnostic Dynamic 3-Dimensional (4-Dimensional) Ultrasound on Ultrastructure of Cerebral Cells of Fetal Mice in Late Pregnancy. AB - The aim of this study was to study the bioeffects of diagnostic dynamic 3 dimensional ultrasound (4D) on ultrastructure of cerebral cells of fetal mice in late pregnancy. Thirty pregnant mice carrying 18th embryonic day fetuses were randomly allocated into 6 groups, namely, control group, sham-exposed group, 5 minute-exposed group, 10 minute-exposed group, 20 minute-exposed group, and 30 minute-exposed groups (5 in each group). In exposure groups, mice were put under the dynamic 3D ultrasound system's probe for 5 to 30 minutes. Mice in sham exposed group did not receive ultrasound wave. At 24th hour after birth, 10 pups of each group were randomly selected (2 in each litter) and euthanized by decapitation, and the brains were immediately removed. Right parietal lobes were taken as specimen. The specimens were firstly fixed with glutaraldehyde and secondly with osmic acid, then sections were made and observed under the transmission electron microscope. There were no obvious abnormal ultrastructure changes in control group, sham-exposed group, and 5 minute-exposed group under transmission electron microscope. Ten minute-exposed group showed some enlarged mitochondria, broken crista, vacuolated endoplasmic resticulums, and a few apoptosis cells. More abnormal organelles and apoptosis cells were observed in 20 minute-exposed and 30 minute-exposed groups (P < 0.05). Dynamic 3D (4D) ultrasound exposure for more than 10 minutes may result in abnormal neuronal ultrastructure changes and apoptosis cells in fetal mouse cerebrum. PMID- 26808171 TI - Point Shear Wave Elastography in Assessment of Hepatic Fibrosis: Diagnostic Accuracy in Subjects With Native and Transplanted Livers Referred for Percutaneous Biopsy. AB - The objective of this study was to prospectively evaluate the use of point shear wave elastography for the assessment of liver fibrosis and to determine the usefulness and optimal location for obtaining elastography measurements in native and transplanted livers. Point shear wave elastography measurements were obtained from 100 consecutive patients presenting for percutaneous liver biopsy. Measurements were acquired within both the superior right hepatic lobe (segments VII/VIII) via an intercostal approach and the inferior right hepatic lobe (segments V/VI) via a subcostal approach. Analysis of variance was used to assess statistical differences between the degree of fibrosis on percutaneous liver biopsy and elastography measurements. No statistical difference was present when comparing elastography measurements in patients with hepatic steatosis compared with patients without steatosis (P = 0.2759). There was no difference in the accuracy of elastography measurements in native livers versus transplanted livers (P = 0.221). Point shear wave elastography can accurately differentiate between patients with no-to-mild hepatic fibrosis (F0-F1) and moderate-to-severe hepatic fibrosis (>=F2) with sensitivity of 72% and specificity of 69%. Point shear wave elastography can be used as a noninvasive method to assess fibrosis in patients with native or transplanted livers. In addition, measurements can be combined or taken separately from either the superior or inferior right hepatic lobe. The presence of hepatic steatosis does not affect the accuracy of point shear wave elastography. However, shear wave elastography values in patients with body mass index greater than 40 should be interpreted with caution. PMID- 26808172 TI - Schwannoma of the Posterior Interosseous Nerve. PMID- 26808173 TI - Orthopaedic Perspective on Barefoot and Minimalist Running. AB - In recent years, there has been a movement toward barefoot and minimalist running. Advocates assert that a lack of cushion and support promotes a forefoot or midfoot strike rather than a rearfoot strike, decreasing the impact transient and stress on the hip and knee. Although the change in gait is theorized to decrease injury risk, this concept has not yet been fully elucidated. However, research has shown diminished symptoms of chronic exertional compartment syndrome and anterior knee pain after a transition to minimalist running. Skeptics are concerned that, because of the effects of the natural environment and the lack of a standardized transition program, barefoot running could lead to additional, unforeseen injuries. Studies have shown that, with the transition to minimalist running, there is increased stress on the foot and ankle and risk of repetitive stress injuries. Nonetheless, despite the large gap of evidence-based knowledge on minimalist running, the potential benefits warrant further research and consideration. PMID- 26808174 TI - Cross-Sectional and Longitudinal Associations between Egg Consumption and Metabolic Syndrome in Adults >= 40 Years Old: The Yangpyeong Cohort of the Korean Genome and Epidemiology Study (KoGES_Yangpyeong). AB - Since the 1970s, the public has been advised to limit egg consumption even though there is little evidence of any harmful effect of eggs on blood cholesterol. The purpose of this cross-sectional and prospective study was to evaluate the potential association between egg consumption and metabolic syndrome (MetS) and MetS components in adults >= 40 years in KoGES_Yangpyeong. Yangpyeong is a rural area in South Korea. A total of 2,887 subjects (men 1,115, women 1,772) were recruited from 2005 to 2009, based on a physical examination and questionnaires administered using standardized protocol. After excluding subjects who had MetS at baseline, 1,663 subjects (675 men, 958 women) were followed for 3.20 years (range: 0.34-8.70). During the follow-up period, MetS occurred in 289 subjects. More than 3 eggs per week was significantly associated with decreased risk of MetS in both men (RR = 0.46, 95% CI, 0.26-0.82, P for trend = 0.1093) and women (RR = 0.54, 95% CI, 0.31-0.93, P for trend 0.0325) compared to non-users. There was a cross-sectional inverse relationship between egg consumption and abdominal obesity in men and women. Also, prospectively, higher egg consumption in men was associated with a decreased risk of high fasting blood glucose (RR = 0.39, 95% CI, 0.22-0.67, P for trend = 0.0042) and high triglycerides (RR = 0.42, 95% CI, 0.22-0.80, P for trend = 0.1080). In conclusion, our findings suggest that higher egg consumption may reduce the risk of MetS both in men and women, and the risk of high fasting blood glucose and high triglycerides in men. Current guidelines regarding egg consumption may need to be re-visited for healthy middle-aged and elderly people. PMID- 26808175 TI - The Mechanics of Brow-Suspension Ptosis Repair: A Comparative Study of Fox Pentagon and Crawford Triangle Techniques. AB - PURPOSE: To perform quantitative analysis of the most commonly used brow suspension configurations. METHODS: The inflection positions for Fox pentagon and Crawford triangle configurations were marked on 49 healthy volunteers (male and female) and photographs taken in 3 states: "normal," "closed," and "raised." The skin marks were measured vectorially with respect to the medial canthus, and displacement changes were evaluated for "normal-to-closed" ("blinking") and from "closed-to-raised" ("eye-opening") states. The distance between a pair of inflection marks, representing the approximate path of sling configurations, were also measured and analyzed in relation to the mechanical properties of a variety of synthetic brow-suspension materials. RESULTS: "Blinking" resulted in the greatest displacement in the medial eyelid incision, resulting in the greatest strain on the line connecting the medial eyelid and medial brow inflections. No significant differences in the strains for individual lines were found between the Fox and Crawford techniques, although the former shows a significantly lower overall strain in the whole loop than the latter. The displacements of some inflections and of the strains of a few lines differed significantly in men and women. CONCLUSIONS: Within the scope of this study, the blinking action was shown to result in the maximum strain of ~40%, which lies within the elastic region of stress-strain curves for some commonly used synthetic brow-suspension materials. No one method was statistically superior, although the Fox pentagon gave a significantly lower overall strain when the sling material was assumed to move somewhat around the inflections within a closed loop. PMID- 26808176 TI - Levator Muscle Enlargement in Thyroid Eye Disease-Related Upper Eyelid Retraction. AB - PURPOSE: To identify levator palpebrae superioris enlargement in thyroid eye disease (TED)-related upper eyelid retraction (ULR). METHODS: Retrospective case control. Subjects included 50 consecutive patients with unilateral thyroid eye disease-related ULR >= 2 mm and no previous eyelid surgery. The contralateral side was used as control. Clinical information was recorded from charts. CT scans were assessed by investigators blinded to the clinical data. A prediction of retracted side was made based on CT scan appearance and on basis of measured levator palpebrae superioris cross-sectional area at 2 defined points. Statistical analysis determined correlation between levator palpebrae superioris size and presence of ULR. The study was approved by the institutional ethics committee. RESULTS: Side with ULR predicted from CT scan review in over 85% of cases. Mean cross-sectional area of levator palpebrae superioris on retracted side was significantly larger than nonretracted side at 2 separate sites. Levator palpebrae superioris area was larger on retracted side compared with nonretracted side in over 85% of subjects. More than 30% of subjects had no enlargement of other extraocular muscles. Only 6% of patients had enlargement of the ipsilateral inferior rectus muscle. CONCLUSIONS: Levator palpebrae superioris enlargement from inflammation or scar is a factor in thyroid eye disease-related ULR. Upper eyelid retraction can be predicted from CT scan appearance in over 85% of cases. Ipsilateral inferior rectus enlargement is rare. Levator palpebrae superioris is the most commonly targeted muscle in thyroid eye disease. PMID- 26808177 TI - Central Retinal Vein Occlusion Resolving After Orbital Decompression in Thyroid Eye Disease. AB - A 49-year-old male presented with proptosis and was found to have optic nerve edema with peripapillary hemorrhages. Diagnostic testing showed a suppressed thyroid-stimulating hormone. CT orbits showed homogenous tendon-sparing enlargement of the medial and inferior rectus muscles, characteristic of thyroid eye disease. Intravenous methylprednisolone was administered given the concern for compressive optic neuropathy. He initially had improvement of his symptoms, so orbital decompression was deferred. Subsequently he presented with worsening diplopia and right proptosis, a new afferent pupillary defect, and a cecocentral visual field defect. Dilated examination revealed significant optic nerve head edema and diffuse retinal hemorrhages in all 4 quadrants consistent with a central retinal vein occlusion. The patient underwent an urgent 3-wall orbital decompression on the right. Close follow up postoperatively showed resolution of the central retinal vein occlusion and the associated optic disc edema, peripapillary hemorrhages, and macular edema. Orbital decompression is known to improve many manifestations of thyroid eye disease, but this is the first report of orbital decompression resulting in resolution of a central retinal vein occlusion. PMID- 26808178 TI - Ocular Adnexal Acne Agminata: Histopathological and Clinical Case Series. AB - PURPOSE: Acne agminata has only been rarely reported in the ocular adnexa. This study was undertaken to identify histopathological, clinical, and management features of this disorder. METHODS: A computerized database was utilized to identify cases of ocular adnexal acne agminata. Via chart review and light microscopy, clinical and histopathologic aspects of this dermatosis were collected, and statistical analyses were performed. RESULTS: Twelve cases (5 males, 7 females, mean age = 50.5 years) of clinically and histopathologically confirmed ocular adnexal acne agminata were identified. The main variant of granuloma was sarcoidal in 6 cases (50%) and tuberculoid in 5 cases (41.7%), although 9 specimens (75%) displayed greater than 1 variant of granuloma. In addition, specimens demonstrated varying degrees of fibrosis (8 cases, 66.7%), necrosis (6 cases, 50%), spongiosis (5 cases, 41.7%), and perifollicular inflammation (6 cases, 50%). All specimens showed signs of lymphstasis lymphangiectasis. At a minimum of 6-month postprocedure interval, all patients experienced complete relief of their symptoms and did not experience recurrence. CONCLUSIONS: This study represents the largest cohort of ocular adnexal acne agminata, and revealed a spectrum of granulomatous subtypes, including coexistence of different granuloma subtypes within the same specimen. Lymphangiectases is a hallmark of this disorder, and varying features of tissue reaction are typical features of acne agminata. All of these cases were successfully cured by surgical resection of lesions without recurrence at last follow-up, and this modality should be considered the standard of care in the management of this problem. PMID- 26808179 TI - Deroofing: An Effective Method for Treating Chronic Diffuse Hidradenitis Suppurativa. PMID- 26808180 TI - Rapid SOX10 Immunostain on Fresh Frozen Tissue. PMID- 26808181 TI - Analysis of 28 Chinese Cases of Bilateral Nevus of Ota and Therapeutic Results With the Q-Switched Alexandrite Laser. AB - BACKGROUND: Nevus of Ota is a dermal melanocytic lesion that presents as bluish hyperpigmentation along the first or second branch of the trigeminal nerve. It is common in Asians. However, bilateral involvement is rare. There has been no detailed report on bilateral involvement in Chinese people. OBJECTIVE: To analyze the clinical data on bilateral nevus of Ota in Chinese patients and determine the efficacy of pulsed q-switched alexandrite laser treatment. METHODS: Twenty-eight cases of bilateral nevus of Ota were diagnosed by clinical appearance, and detailed clinical data were collected. A q-switched alexandrite laser was used for treatment. RESULTS: The incidence of bilateral nevus of Ota was 1.4% (28 of 1985). More than 3 regions were involved in most patients (96.4%), and symmetrical lesions were observed in approximately 60% of cases (17 of 28). The lesion was seen at or soon after birth in 15 patients (53.6%); two-thirds of these patients (10 of 15) had ocular or mucosal involvement. The therapeutic results were excellent or good in 17 cases; the group that received more than 3 treatments and age of starting treatment being less than 6 years had better therapeutic results. CONCLUSION: The pulsed q-switched alexandrite laser is an effective treatment, and earlier intervention with more sessions achieves better results. PMID- 26808182 TI - Treatment of Persistent Facial Postinflammatory Hyperpigmentation With Novel Pulse-in-Pulse Mode Intense Pulsed Light. AB - BACKGROUND: Postinflammatory hyperpigmentation (PIH) is an acquired hypermelanosis induced by various causes including inflammatory dermatoses, injury, or cosmetic procedures, such as lasers or chemical peels, and it tends to affect dark-skinned people with greater frequency and severity. There are a variety of treatment options for PIH, including topical agents, chemical peels, laser, and light therapy. However, the results are not up to expectation. OBJECTIVE: The purpose of this study was to examine the clinical efficacy and safety of novel pulse-in-pulse mode intense pulsed light (IPL) for the treatment of persistent facial PIH in Korean patients. MATERIALS AND METHODS: Twenty-five Korean female patients (Fitzpatrick skin types III-V) with persistent facial PIH were enrolled in the study. The patients were treated with novel pulse-in-pulse mode IPL for 4 sessions at 1-week interval and 4 sessions at 2-week intervals. Treatment efficacy and patient satisfaction were evaluated using photographs and questionnaires. RESULTS: After 2 months of all treatments, 23 patients (92%) had more than 50% improvement and 22 patients (88%) were satisfied with the treatments. No adverse effects or aggravations were reported. CONCLUSION: The pulse-in-pulse mode IPL treatment is effective and safe for persistent facial PIH in dark-skinned patients. PMID- 26808183 TI - Dermatofibrosarcoma Protruberans of the Forehead With Extensive Subclinical Spread. PMID- 26808184 TI - Staged Excision in the Outpatient Setting for the Treatment of Axillary Hidradenitis Suppurativa. PMID- 26808185 TI - Intralesional Injection for Inflammatory Nail Diseases. PMID- 26808186 TI - A Novel External Approach for Buried Dermal Sutures to Close Small Skin Wounds. PMID- 26808187 TI - The Wave Flap: A Single-Stage, Modified Nasal Sidewall Rotation Flap for the Repair of Defects Involving the Mid-Alar Groove. AB - BACKGROUND: Reconstruction of defects straddling the alar groove presents the dual challenges of resurfacing the nasal sidewall and alar subunits while simultaneously recreating the alar groove. The wave flap (WF) is a modified, medially based, nasal sidewall rotation flap that uses locally recruited tissue from the nasal sidewall to facilitate color and texture match and permit camouflage of scars. OBJECTIVE: To detail a surgical repair for defects in the horizontally oriented middle third of the alar groove. MATERIALS AND METHODS: This retrospective case series describes a technique for repair of defects involving the alar groove. Using postoperative photographs, outcomes were assessed by blinded noninvestigator dermatologist raters using the Observer Scar Assessment Scale. RESULTS: Between February 2012 and June 2013, 10 patients were reconstructed using a WF design. Subjective assessment of scar vascularity, pigment, pliability, relief, and thickness by 3 independent reviewers yielded an overall cosmesis score of 11.1 (out of 50). No complications were noted. CONCLUSION: The WF provides an excellent reconstructive option for Mohs defects of the middle third of the alar groove by recruiting local tissue and permitting maximum scar camouflage. A well-designed and executed WF provides cosmetically exceptional results for defects of the alar groove. PMID- 26808188 TI - The Interpersonal Adaptiveness of Dispositional Guilt and Shame: A Meta-Analytic Investigation. AB - Despite decades of empirical research, conclusions regarding the adaptiveness of dispositional guilt and shame are mixed. We use meta-analysis to summarize the empirical literature and clarify these ambiguities. Specifically, we evaluate how guilt and shame are uniquely related to pro-social orientation and, in doing so, highlight the substantial yet under-acknowledged impact of researchers' methodological choices. A series of meta-analyses was conducted investigating the relationship between dispositional guilt (or shame) and pro-social orientation. Two main methodological moderators of interest were tested: test format (scenario vs. checklist) and statistical analysis (semi-partial vs. zero-order correlations). Among studies employing zero-order correlations, dispositional guilt was positively correlated with pro-social orientation (k = 63, Mr = .13, p < .001), whereas dispositional shame was negatively correlated, (k = 47, Mr = .05, p = .07). Test format was a significant moderator for guilt studies only, with scenario measures producing significantly stronger effects. Semi-partial correlations resulted in significantly stronger effects among guilt and shame studies. Although dispositional guilt and shame are differentially related to pro social orientation, such relationships depend largely on the methodological choices of the researcher, particularly in the case of guilt. Implications for the study of these traits are discussed. PMID- 26808189 TI - Clinically relevant analytical techniques, organizational concepts for application and future perspectives of point-of-care testing. AB - Applications of near-patient testing have developed rapidly during the last years. It offers quick test results and minimal preanalytical interference, having the potential to improve patient outcomes, even when still under scrutiny by laboratory and healthcare professionals. Near-patient diagnostics are currently also used increasingly in developing countries, due to the burden of inadequate healthcare services in resource-constrained settings. This review describes the underlying emerging techniques that are based on advanced microfluidics and nanomaterials, device miniaturization, and multiplexing the detection mode. The organizational concepts for reasonable applications, contributing significantly to the future perspectives of this nascent diagnostic modality, are supplementary portrayed. PMID- 26808190 TI - Patch-based anisotropic diffusion scheme for fluorescence diffuse optical tomography--part 2: image reconstruction. AB - Fluorescence diffuse optical tomography (fDOT) provides 3D images of fluorescence distributions in biological tissue, which represent molecular and cellular processes. The image reconstruction problem is highly ill-posed and requires regularisation techniques to stabilise and find meaningful solutions. Quadratic regularisation tends to either oversmooth or generate very noisy reconstructions, depending on the regularisation strength. Edge preserving methods, such as anisotropic diffusion regularisation (AD), can preserve important features in the fluorescence image and smooth out noise. However, AD has limited ability to distinguish an edge from noise. We propose a patch-based anisotropic diffusion regularisation (PAD), where regularisation strength is determined by a weighted average according to the similarity between patches around voxels within a search window, instead of a simple local neighbourhood strategy. However, this method has higher computational complexity and, hence, we wavelet compress the patches (PAD-WT) to speed it up, while simultaneously taking advantage of the denoising properties of wavelet thresholding. Furthermore, structural information can be incorporated into the image reconstruction with PAD-WT to improve image quality and resolution. In this case, the weights used to average voxels in the image are calculated using the structural image, instead of the fluorescence image. The regularisation strength depends on both structural and fluorescence images, which guarantees that the method can preserve fluorescence information even when it is not structurally visible in the anatomical images. In part 1, we tested the method using a denoising problem. Here, we use simulated and in vivo mouse fDOT data to assess the algorithm performance. Our results show that the proposed PAD WT method provides high quality and noise free images, superior to those obtained using AD. PMID- 26808191 TI - Fitness Effects of Food Resources on the Polyphagous Aphid Parasitoid, Aphidius colemani Viereck (Hymenoptera: Braconidae: Aphidiinae). AB - Conservation biological control involving the polyphagous aphid parasitoid, Aphidius colemani Viereck, may include provisioning resources from a variety of plant sources. The fitness of adult A. colemani was enhanced with the provision of food resources such as floral nectar from a range of both native and introduced plant species and aphid honeydew under laboratory conditions. However, enhanced fitness appeared to be species specific rather than associated with the whether the plant was a native or an introduced species. Parasitoid survival and fecundity were enhanced significantly in response to the availability of floral nectar and honeydew compared to the response to available extrafloral nectar. These positive effects on the parasitoid's reproductive activity can improve the effectiveness of conservation biological control in nursery production systems because of the abundance and diversity of floral resources within typical production areas. Additionally, surrounding areas of invasive weeds and native vegetation could serve as both floral resources and honeydew food resources for A. colemani. PMID- 26808192 TI - Molecular Characterization of the N-Acetylglucosamine Catabolic Genes in Candida africana, a Natural N-Acetylglucosamine Kinase (HXK1) Mutant. AB - BACKGROUND: In this study we report the genetic characterization, including expression analysis, of the genes involved in the uptake (NGT1) and catabolism (HXK1/NAG5, DAC1/NAG2, NAG1) of the aminosugar N-acetylglucosamine (GlcNAc) in Candida africana, a pathogenic biovariant of Candida albicans that is naturally unable to assimilate the GlcNAc. RESULTS: DNA sequence analysis of these genes revealed a number of characteristic nucleotide substitutions including a unique and distinctive guanine insertion that shifts the reading frame and generates a premature stop codon (TGA) 154 bp downstream of the ATG start codon of the HXK1 gene encoding the GlcNAc-kinase, a key enzyme of the GlcNAc catabolic pathway. However, all examined genes produced transcripts even though different levels of expression were observed among the Candida isolates examined. In particular, we found an HXK1-idependent relationship of the NGT1 gene and a considerable influence of the GlcNAc-kinase functionality on the transcription of the DAC1 and NAG1 genes. Additional phenotypic analysis revealed that C. africana isolates are hyperfilamentous in the first 24-48h of growth on filament-inducing media and revert to the yeast morphological form after 72h of incubation on these media. CONCLUSIONS: Our results show that C. africana is a natural HXK1 mutant, displaying a number of phenotypic characteristics distinct from typical C. albicans isolates. PMID- 26808193 TI - Polyphyllin VII Induces an Autophagic Cell Death by Activation of the JNK Pathway and Inhibition of PI3K/AKT/mTOR Pathway in HepG2 Cells. AB - Polyphyllin VII (PP7), a pennogenyl saponin isolated from Rhizoma Paridis, exhibited strong anticancer activities in various cancer types. Previous studies found that PP7 induced apoptotic cell death in human hepatoblastoma cancer (HepG2) cells. In the present study, we investigated whether PP7 could induce autophagy and its role in PP7-induced cell death, and elucidated its mechanisms. PP7 induced a robust autophagy in HepG2 cells as demonstrated by the conversion of LC3B-I to LC3B-II, degradation of P62, formation of punctate LC3-positive structures, and autophagic vacuoles tested by western blot analysis or InCell 2000 confocal microscope. Inhibition of autophagy by treating cells with autophagy inhibitor (chloroquine) abolished the cell death caused by PP7, indicating that PP7 induced an autophagic cell death in HepG2 cells. C-Jun N terminal kinase (JNK) was activated after treatment with PP7 and pretreatment with SP600125, a JNK inhibitor, reversed PP7-induced autophagy and cell death, suggesting that JNK plays a critical role in autophagy caused by PP7. Furthermore, our study demonstrated that PP7 increased the phosphorylation of AMPK and Bcl-2, and inhibited the phosphorylation of PI3K, AKT and mTOR, suggesting their roles in the PP7-induced autophagy. This is the first report that PP7 induces an autophagic cell death in HepG2 cells via inhibition of PI3K/AKT/mTOR, and activation of JNK pathway, which induces phosphorylation of Bcl-2 and dissociation of Beclin-1 from Beclin-1/Bcl-2 complex, leading to induction of autophagy. PMID- 26808194 TI - Optimizing Subsequent Pregnancy Outcomes for Women with a Prior Preterm Birth. AB - Women with a prior preterm birth are at increased risk of recurrent preterm delivery in a subsequent pregnancy. Interventions during the preconception and prenatal periods can decrease this risk. Review of the circumstances of the prior delivery can elucidate whether delivery was spontaneous or indicated, anticipate recurrence risk, and guide management in a subsequent pregnancy. Preconception interventions for women with prior preterm birth should include cessation of tobacco and substance abuse, control of underlying maternal comorbidities, and encouraging a healthy body mass index. Effective contraception, including use of long-acting reversible methods, should be encouraged to facilitate planned pregnancies with optimal interpregnancy intervals. Interventions during prenatal care include screening and treatment of infections, nutritional supplementation, and enhanced prenatal care. Women with prior spontaneous preterm birth may benefit from progesterone supplementation and serial cervical length screening, while women with prior indicated preterm birth may benefit from daily aspirin. PMID- 26808195 TI - Tocolysis for Acute Preterm Labor: Where Have We Been, Where Are We Now, and Where are We Going? AB - Tocolytics have been used for over 60 years for women with preterm labor, which ultimately can lead to preterm birth (PTB). Diagnosing preterm labor is challenging, but use of objective tests such as transvaginal ultrasound of cervical length assists in the identification of women at the highest risk for PTB. Once preterm labor has been diagnosed, clinicians can choose from a variety of drug classes (cyclooxygenase inhibitors, calcium channel blockers, and betamimetics) to achieve the primary goal of delaying delivery by 48 hours, thereby allowing time for administration of corticosteroids for fetal lung maturity, and if appropriate, starting magnesium sulfate for fetal neuroprotection. Cyclooxygenase inhibitors are the only class of tocolytics proven to decrease PTB < 37 weeks. Knowledge of the safety and effectiveness of these medications is paramount. Several additional agents (e.g., oxytocin receptor antagonists) have significant promise, but further studies are required before these medications can be approved for tocolysis in the United States. As we look into the future of tocolysis, we anticipate that deeper understanding of the complex physiology of preterm labor will allow us to uniquely target different etiologies that lead to the final path resulting in spontaneous preterm delivery. PMID- 26808196 TI - Templated Formation of Discrete RNA and DNA:RNA Hybrid G-Quadruplexes and Their Interactions with Targeting Ligands. AB - G-rich RNA and DNA oligonucleotides derived from the human telomeric sequence were assembled onto addressable cyclopeptide platforms through oxime ligations and copper-catalyzed azide-alkyne cycloaddition (CuAAc) reactions. The resulting conjugates were able to fold into highly stable RNA and DNA:RNA hybrid G quadruplex (G4) architectures as demonstrated by UV, circular dichroism (CD), and NMR spectroscopic analysis. Whereas rationally designed parallel RNA and DNA:RNA hybrid G4 topologies could be obtained, we could not force the formation of an antiparallel RNA G4 structure, thus supporting the idea that this topology is strongly disfavored. The binding affinities of four representative G4 ligands toward the discrete RNA and DNA:RNA hybrid G4 topologies were compared to the one obtained with the corresponding DNA G4 structure. Surface plasmon resonance (SPR) binding analysis suggests that the accessibility to G4 recognition elements is different among the three structures and supports the idea that G4 ligands might be shaped to achieve structure selectivity in a biological context. PMID- 26808197 TI - Allometric Scaling of Patrolling Rate and Nest Volume in Constrictotermes cyphergaster Termites: Hints on the Settlement of Inquilines. AB - Structural and functional traits of organisms are known to be related to the size of individuals and to the size of their colonies when they belong to one. Among such traits, propensity to inquilinism in termites is known to relate positively to colony size. Larger termitaria hold larger diversity of facultative inquilines than smaller nests, whereas obligate inquilines seem unable to settle in nests smaller than a threshold volume. Respective underlying mechanisms, however, remain hypothetical. Here we test one of such hypotheses, namely, that nest defence correlates negatively to nest volume in Constrictotermes cyphergaster termites (Termitidae: Nasutitermitinae). As a surrogate to defence, we used 'patrolling rate', i.e., the number of termite individuals attending per unit time an experimentally damaged spot on the outer wall of their termitaria. We found that patrolling rate decayed allometrically with increasing nest size. Conspicuously higher patrolling rates occurred in smaller nests, while conspicuously lower rates occurred in larger nests presenting volumes in the vicinity of the threshold value for the establishment of inquilinism. This could be proven adaptive for the host and guest. At younger nest age, host colonies are smaller and presumably more vulnerable and unstable. Enhanced defence rates may, hence, prevent eventual risks to hosts from inquilinism at the same time that it prevents inquilines to settle in a still unstable nest. Conversely, when colonies grow and maturate enough to stand threats, they would invest in priorities other than active defence, opening an opportunity for inquilines to settle in nests which are more suitable or less risky. Under this two-fold process, cohabitation between host and inquiline could readily stabilize. PMID- 26808198 TI - Dynamics of the Tec-family tyrosine kinase SH3 domains. AB - The Src Homology 3 (SH3) domain is an important regulatory domain found in many signaling proteins. X-ray crystallography and NMR structures of SH3 domains are generally conserved but other studies indicate that protein flexibility and dynamics are not. We previously reported that based on hydrogen exchange mass spectrometry (HX MS) studies, there is variable flexibility and dynamics among the SH3 domains of the Src-family tyrosine kinases and related proteins. Here we have extended our studies to the SH3 domains of the Tec family tyrosine kinases (Itk, Btk, Tec, Txk, Bmx). The SH3 domains of members of this family augment the variety in dynamics observed in previous SH3 domains. Txk and Bmx SH3 were found to be highly dynamic in solution by HX MS and Bmx was unstructured by NMR. Itk and Btk SH3 underwent a clear EX1 cooperative unfolding event, which was localized using pepsin digestion and mass spectrometry after hydrogen exchange labeling. The unfolding was localized to peptide regions that had been previously identified in the Src-family and related protein SH3 domains, yet the kinetics of unfolding were not. Sequence alignment does not provide an easy explanation for the observed dynamics behavior, yet the similarity of location of EX1 unfolding suggests that higher-order structural properties may play a role. While the exact reason for such dynamics is not clear, such motions can be exploited in intra- and intermolecular binding assays of proteins containing the domains. PMID- 26808199 TI - Phenylbutazone, a New Long-Acting Agent that can Improve the Peptide Pharmacokinetic Based on Serum Albumin as a Drug Carrier. AB - As a NPY-2 receptor agonist, PYY24-36- Leu31 is reported to suppress appetite and has a potential in obesity treatment, but its short half-life limits the clinical application. The use of chemical modification to improve interactions with human serum albumin (HSA) is an effective strategy for prolonging the half-lives of peptide analogues. So based on the characteristics that phenylbutazone has a good combination with HSA, we selected a proper linker to link with PYY24-36 -Leu31 to create long-acting and highly biologically active PYY24-36 -Leu31 conjugates, and successfully find a novel, long-acting PYY24-36 -Leu31 conjugate 8 that, when dosed every other day in diet induce obese (DIO) mice for 2 weeks, results in a significant reduction in food intake and body weight and improvement in blood parameter and hepatic steatosis. PMID- 26808200 TI - Hemoglobin E Prevalence among Ethnic Groups Residing in Malaria-Endemic Areas of Northern Thailand and Its Lack of Association with Plasmodium falciparum Invasion In Vitro. AB - Hemoglobin E (HbE) is one of the most common hemoglobin variants caused by a mutation in the beta-globin gene, and found at high frequencies in various Southeast Asian groups. We surveyed HbE prevalence among 8 ethnic groups residing in 5 villages selected for their high period malaria endemicity, and 5 for low endemicity in northern Thailand, in order to uncover factors which may affect genetic persistence of HbE in these groups. We found the overall HbE prevalence 6.7%, with differing frequencies from 0% in the Pwo Karen, the Lawa, and the Skaw Karen to 24% in the Mon. All HbE genes were heterozygous (AE). Differences in HbE prevalence among the studied ethnic groups indirectly documents that ancestries and evolutionary forces, such as drift and admixture, are the important factors in the persistence of HbE distribution in northern Thailand. Furthermore, the presence of HbE in groups of northern Thailand had no effect on the in vitro infectivity and proliferation of Plasmodium falciparum, nor the production of hemozoin, a heme crystal produced by malaria parasites, when compared to normal red-blood-cell controls. Our data may contribute to a better understanding on the persistence of HbE among ethnic groups and its association with malaria. PMID- 26808201 TI - Characterization of the Antiglioma Effect of the Oncolytic Adenovirus VCN-01. AB - Despite the recent advances in the development of antitumor therapies, the prognosis for patients with malignant gliomas remains dismal. Therapy with tumor selective viruses is emerging as a treatment option for this devastating disease. In this study we characterize the anti-glioma effect of VCN-01, an improved hyaluronidase-armed pRB-pathway-selective oncolytic adenovirus that has proven safe and effective in the treatment of several solid tumors. VCN-01 displayed a significant cytotoxic effect on glioma cells in vitro. In vivo, in two different orthotopic glioma models, a single intra-tumoral administration of VCN-01 increased overall survival significantly and led to long-term survivors free of disease. PMID- 26808202 TI - Archaeal Mo-Containing Glyceraldehyde Oxidoreductase Isozymes Exhibit Diverse Substrate Specificities through Unique Subunit Assemblies. AB - Archaea use glycolytic pathways distinct from those found in bacteria and eukaryotes, where unique enzymes catalyze each reaction step. In this study, we isolated three isozymes of glyceraldehyde oxidoreductase (GAOR1, GAOR2 and GAOR3) from the thermoacidophilic archaeon Sulfolobus tokodaii. GAOR1-3 belong to the xanthine oxidoreductase superfamily, and are composed of a molybdo-pyranopterin subunit (L), a flavin subunit (M), and an iron-sulfur subunit (S), forming an LMS hetero-trimer unit. We found that GAOR1 is a tetramer of the STK17810/STK17830/STK17820 hetero-trimer, GAOR2 is a dimer of the STK23390/STK05620/STK05610 hetero-trimer, and GAOR3 is the STK24840/STK05620/STK05610 hetero-trimer. GAOR1-3 exhibited diverse substrate specificities for their electron donors and acceptors, due to their different L subunits, and probably participate in the non-phosphorylative Entner-Doudoroff glycolytic pathway. We determined the crystal structure of GAOR2, as the first three-dimensional structure of an archaeal molybdenum-containing hydroxylase, to obtain structural insights into their substrate specificities and subunit assemblies. The gene arrangement and the crystal structure suggested that the M/S complex serves as a structural scaffold for the binding of the L-subunit, to construct the three enzymes with different specificities. Collectively, our findings illustrate a novel principle of a prokaryotic multicomponent isozyme system. PMID- 26808203 TI - Pulsed-Plasma Physical Vapor Deposition Approach Toward the Facile Synthesis of Multilayer and Monolayer Graphene for Anticoagulation Applications. AB - We demonstrate the growth of multilayer and single-layer graphene on copper foil using bipolar pulsed direct current (DC) magnetron sputtering of a graphite target in pure argon atmosphere. Single-layer graphene (SG) and few-layer graphene (FLG) films are deposited at temperatures ranging from 700 degrees C to 920 degrees C within <30 min. We find that the deposition and post-deposition annealing temperatures influence the layer thickness and quality of the graphene films formed. The films were characterized using atomic force microscopy (AFM), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and optical transmission spectroscopy techniques. Based on the above studies, a diffusion-controlled mechanism was proposed for the graphene growth. A single step whole blood assay was used to investigate the anticoagulant activity of graphene surfaces. Platelet adhesion, activation, and morphological changes on the graphene/glass surfaces, compared to bare glass, were analyzed using fluorescence microscopy and SEM techniques. We have found significant suppression of the platelet adhesion, activation, and aggregation on the graphene-covered surfaces, compared to the bare glass, indicating the anticoagulant activity of the deposited graphene films. Our production technique represents an industrially relevant method for the growth of SG and FLG for various applications including the biomedical field. PMID- 26808204 TI - Outlining a core neuropsychological phenotype for Dravet syndrome. AB - An up-to-date review on neuropsychological phenotypes in Dravet syndrome is reported. After recalling the results of various though not numerous studies in the literature, primarily retrospectively, the hypothesis of an original neuropsychological phenotype in Dravet syndrome is presented, consisting of a defect in sensorimotor integration, especially of visuoconstructive abilities. That is particularly evident in the less impaired patients and in the first several years of life. This core phenotype is eventually considered inside the analysis of the etiological multifactorial origin of the cognitive decline, which is especially expressed by the encephalopathy/channelopathy controversy. PMID- 26808205 TI - Pontine and cerebral atrophy in Lennox-Gastaut syndrome. AB - OBJECTIVES: Lennox-Gastaut syndrome (LGS) is a severe epilepsy of childhood onset associated with intellectual disability and multiple seizure types. Characteristic interictal electrographic discharges include generalized paroxysmal fast activity and slow spike and wave, which we have previously shown recruit widespread areas of association cortex. We wished to determine whether patients with Lennox-Gastaut syndrome (LGS) have changes in cerebral volumes that match this pattern of cortical recruitment. METHODS: High resolution T1 weighted structural MRI was collected from 10 patients with LGS and 10 age and sex matched controls. Voxel-based morphometry (VBM) was used to compare tissue volumes across the whole brain (grey matter, white matter and CSF) and pontine volume between patients and controls, as well as to identify other regions of maximal tissue loss. RESULTS: LGS patients showed a significant decrease in whole brain volume compared to controls. Cortical atrophy was prominent in the mesial frontal region and bilateral anterior temporal poles. White matter atrophy was widespread and included peri-central and premotor regions. Atrophy was prominent in the pons, particularly in the region of the reticular formation. Grey matter atrophy trended to progress with age. SIGNIFICANCE: Grey and white matter atrophy are a feature of Lennox-Gastaut syndrome. Grey matter atrophy is apparent in the mesial frontal lobe suggesting this region may be an important node in the epilepsy network of LGS. Atrophy maximal in the pons and cerebellum mimics the patterns of seizure spread that has been previously observed during tonic seizures. This supports the idea that the pons is a key part of the epilepsy network in LGS. PMID- 26808206 TI - Associations Between Perceived Weight Status, Body Dissatisfaction, and Self Objectification on Sexual Sensation Seeking and Sexual Risk Behaviors Among Men Who Have Sex with Men Using Grindr. AB - To date, various dimensions of body image and their associations with condom use have not been studied among men who have sex with men (MSM) who use geosocial networking smartphone applications ("apps") to meet new sexual partners. The purpose of the current study was to evaluate associations between weight perception, body dissatisfaction, and self-objectification with sexual behaviors among a sample of MSM (N = 92) recruited from Grindr, an app popular among MSM, to complete an online survey. Obese participants scored significantly higher on measures of body dissatisfaction and lower on measures of sexual sensation seeking. Decreased propensities to seek sexual sensations were associated with fewer sexual partners. By assessing associations between dimensions of body dissatisfaction and sexual risk behaviors, this study adds support to a theory of syndemics among MSM, which suggests that synergistically related biological, psychological, social, and behavioral factors disproportionately affect health and health-related behaviors in this population. PMID- 26808207 TI - Optical and photophysical properties of anisole- and cyanobenzene-substituted perylene diimides. AB - One- and two-photon absorption cross-sections and spectra and the photophysical properties of eight perylenetetracarboxy-3,4:9,10-diimide (PDI) derivatives are reported and analyzed. The investigated compounds are characterized by direct binding of the phenyl rings of the substituents to the bay positions of the perylene core. They have been designed to test the effects of differences in the electronic nature - electron donating (anisole) or accepting (cyanobenzene) - and binding topology (cis or trans, meta or para disubstitution or tetrasubstitution) of the bay substituents on the above optical and photophysical observables. (TD)DFT and Huckel MO calculations have provided theoretical information on the ground-state geometries, the MOs and the electronic spectra of several model compounds. For tetrasubstituted and cis disubstituted derivatives, strong steric interactions in the bay area determined the preferred conformations, with perylene cores distorted near the substituted bay(s) and a 42-44 degrees twisting of the substituent rings relative to the core, quite irrespective of the electronic nature of the substituents. On the other hand, in trans-disubstituted PDI steric hindrance in the bay areas was much weaker and similar in the cyanobenzene and the anisole derivatives. So, the large differences found in the conformational preferences were completely attributable to electronic effects. With electron-accepting cyanobenzene, the substituent rings were found normal to the central planar perylene core, thus enabling the assignment of the moderate spectroscopic effects to inductive interactions. The DFT analysis of the PDI trans-disubstituted with electron-donating anisoles gave quite strongly distorted perylene-core geometries and less twisted (59 degrees ) substituent rings. The corresponding increased substituent/core conjugative interactions resulted in new CT allowed electronic transitions and an extremely pronounced solvent-polarity dependence of the emission spectra and intensities. All anisole substituted PDI feature a very fast radiationless decay path in polar solvents, likely related to a relaxation to a charge-separated configuration in the lowest excited-state. PMID- 26808209 TI - Class III HD-Zip activity coordinates leaf development in Physcomitrella patens. AB - Land plant bodies develop from meristems, groups of pluripotent stem cells, which may persist throughout the life of a plant or, alternatively, have a transitory existence. Early diverging land plants exhibit indeterminate (persistent) growth in their haploid gametophytic generation, whereas later diverging lineages exhibit indeterminate growth in their diploid sporophytic generation, raising the question of whether genetic machinery directing meristematic functions was co opted between generations. Class III HD-Zip (C3HDZ) genes are required for the establishment and maintenance of shoot apical meristems in flowering plants. We demonstrate that in the moss Physcomitrella patens, C3HDZ genes are expressed in transitory meristems in both the gametophytic and sporophytic generations, but not in the persistent shoot meristem of the gametyphyte. Loss-of-function of P. patens C3HDZ was engineered using ectopic expression of miR166, an endogenous regulator of C3HDZ gene activity. Loss of C3HDZ gene function impaired the function of gametophytic transitory meristematic activity but did not compromise the functioning of the persistent shoot apical meristem during the gametophyte generation. These results argue against a wholesale co-option of meristematic gene regulatory networks from the gametophyte to the sporophyte during land plant evolution, instead suggesting that persistent meristems with a single apical cell in P. patens and persistent complex meristems in flowering plants are regulated by different genetic programs. PMID- 26808210 TI - Anti-vascular endothelial growth factor treatment induces blood flow recovery through vascular remodeling in high-fat diet induced diabetic mice. AB - Diabetes mellitus (DM) leads to the development of microvascular diseases and is associated with impaired angiogenesis. The presence of vascular endothelial growth factor (VEGF) can block PDGF-BB dependent regulation of neovascularization and vessel normalization. We tested the hypothesis that the inhibition of VEGF improves blood flow in a mouse hindlimb ischemia model produced by femoral artery ligation. In this study, we examined the effect of bevacizumab, a humanized monoclonal antibody against VEGF-A, on blood perfusion and angiogenesis after hindlimb ischemia. We showed that bevacizumab induces functional blood flow in high fat chow (HFC)-fed diabetic mice. Treatment with bevacizumab increased the expression of platelet derived growth factor-BB (PDGF-BB) in ischemic muscle, and led to vascular normalization. It also blocked vascular leakage by improving the recruitment of pericytes associated with nascent blood vessels, but it did not affect capillary formation. Furthermore, treatment with an anti-PDGF drug significantly inhibited blood flow perfusion in diabetic mice treated with bevacizumab. These results indicate that bevacizumab improves blood flow recovery through the induction of PDGF-BB in a diabetic mouse hindlimb ischemia model, and that vessel normalization may represent a useful strategy for the prevention and treatment of diabetic peripheral arterial disease. PMID- 26808212 TI - Coronene-Containing N-Heteroarenes: 13 Rings in a Row. AB - We describe the modular synthesis of three novel large N-heteroarenes, containing 9, 11, and 13 annulated rings. This modular system features fused azaacene units to a coronene nucleus. We evaluate the optical and electronic properties and the solid-state packing of the targets. The electronic properties of the 13-ring N heteroarene allow the fabrication of a proof-of-concept thin-film transistor. Electron mobilities up to 8 * 10(-4) cm/(V s) were obtained for polycrystalline films. PMID- 26808211 TI - The effect of heating rate on the cutaneous vasomotion responses of forearm and leg skin in humans. AB - We examined skin blood flow (SkBF) and vasomotion in the forearm and leg using laser-Doppler fluxmetry (LDF) and spectral analysis to investigate endothelial, sympathetic, and myogenic activities in response to slow (0.1 degrees C.10 s( 1)) and fast (0.5 degrees C.10 s(-1)) local heating. At 33 degrees C (thermoneutral) endothelial activity was higher in the legs than the forearms (P <= 0.02). Fast-heating increased SkBF more than slow heating (P=0.037 forearm; P=0.002 leg). At onset of 42 degrees C, endothelial (P=0.043 forearm; P=0.48 leg) activity increased in both regions during the fast-heating protocol. Following prolonged heating (42 degrees C) endothelial activity was higher in both the forearm (P=0.002) and leg (P<0.001) following fast-heating. These results confirm regional differences in the response to local heating and suggest that the greater increase in SkBF in response to fast local heating is initially due to increased endothelial and sympathetic activity. Furthermore, with sustained local skin heating, greater vasodilatation was observed with fast heating compared to slow heating. These data indicate that this difference is due to greater endothelial activity following fast heating compared to slow heating, suggesting that the rate of skin heating may alter the mechanisms contributing to cutaneous vasodilatation. PMID- 26808208 TI - The old and new face of craniofacial research: How animal models inform human craniofacial genetic and clinical data. AB - The craniofacial skeletal structures that comprise the human head develop from multiple tissues that converge to form the bones and cartilage of the face. Because of their complex development and morphogenesis, many human birth defects arise due to disruptions in these cellular populations. Thus, determining how these structures normally develop is vital if we are to gain a deeper understanding of craniofacial birth defects and devise treatment and prevention options. In this review, we will focus on how animal model systems have been used historically and in an ongoing context to enhance our understanding of human craniofacial development. We do this by first highlighting "animal to man" approaches; that is, how animal models are being utilized to understand fundamental mechanisms of craniofacial development. We discuss emerging technologies, including high throughput sequencing and genome editing, and new animal repository resources, and how their application can revolutionize the future of animal models in craniofacial research. Secondly, we highlight "man to animal" approaches, including the current use of animal models to test the function of candidate human disease variants. Specifically, we outline a common workflow deployed after discovery of a potentially disease causing variant based on a select set of recent examples in which human mutations are investigated in vivo using animal models. Collectively, these topics will provide a pipeline for the use of animal models in understanding human craniofacial development and disease for clinical geneticist and basic researchers alike. PMID- 26808213 TI - Immunophilin-like FKBP42/TWISTED DWARF1 Interacts with the Receptor Kinase BRI1 to Regulate Brassinosteroid Signaling in Arabidopsis. AB - Mutation of the immunophilin-like FK506-binding protein TWISTED DWARF1 (FKBP42/TWD1) causes dwarf and twisted-organ phenotypes in Arabidopsis. However, the function of FKBP42 is not fully understood at the molecular level. Using genetic, physiological, and immunological experiments, we show here that FKBP42/TWD1 is necessary for brassinosteroid (BR) signal transduction. The twd1 mutant showed reduced BR sensitivity in growth responses and activation of the BZR1 transcription factor. However, twd1 showed normal responses to an inhibitor of BIN2/GSK3, suggesting that twd1 has a defect upstream of BIN2 in the BR signaling pathway. In vitro and in vivo assays showed that TWD1 interacts physically with the kinase domains of the BR receptor kinases BRI1 and BAK1. TWD1 is not required for normal localization of BRI1-GFP to the plasma membrane or for activation of the flagellin receptor kinase FLS2. Our results suggest that FKBP42/TWD1 plays a specific role in the activation of BRI1 receptor kinase. PMID- 26808215 TI - Broadband Absorbing Exciton-Plasmon Metafluids with Narrow Transparency Windows. AB - Optical metafluids that consist of colloidal solutions of plasmonic and/or excitonic nanomaterials may play important roles as functional working fluids or as means for producing solid metamaterial coatings. The concept of a metafluid employed here is based on the picture that a single ballistic photon, propagating through the metafluid, interacts with a large collection of specifically designed optically active nanocrystals. We demonstrate water-based metafluids that act as broadband electromagnetic absorbers in a spectral range of 200-3300 nm and feature a tunable narrow (~100 nm) transparency window in the visible-to-near infrared region. To define this transparency window, we employ plasmonic gold nanorods. We utilize excitonic boron-doped silicon nanocrystals as opaque optical absorbers ("optical wall") in the UV and blue-green range of the spectrum. Water itself acts as an opaque "wall" in the near-infrared to infrared. We explore the limits of the concept of a "simple" metafluid by computationally testing and validating the effective medium approach based on the Beer-Lambert law. According to our simulations and experiments, particle aggregation and the associated decay of the window effect are one example of the failure of the simple metafluid concept due to strong interparticle interactions. PMID- 26808214 TI - Enhancement of photodynamic inactivation against Pseudomonas aeruginosa by a nano carrier approach. AB - As pathogens steadily develop resistance to widely used antibiotics, new methodologies for their efficient inactivation must be developed. Photodynamic therapy is an upcoming technique that provides an alternative option for treating pathogenic infections. The efficiency of photodynamic therapy has been limited by the use of aqueous mediums for dispersing photosensitising agents. Toluidine Blue O (TBO) was chosen for this study as a cationic photosensitiser to inhibit Gram negative bacterium Pseudomonas aeruginosa. Enhanced delivery of the photosensitiser was ensured by utilising an essential oil-based microemulsion. The efficiency of photodynamic therapy was further improved by the use of a chemical penetration enhancer to improve permeability of the bacterial outer membrane. TBO accumulation patterns in neonate pig skin were studied using confocal laser scanning microscopy. The physicochemical properties of the TBO loaded microemulsion, including UV-vis absorbance, size distribution and zeta potential, were analysed to understand the enhanced antimicrobial activity. Confocal laser scanning microscopy confirmed the formation of a TBO reservoir in the skin by the TBO-loaded microemulsions. TBO (5 MUg/mL) in the vehicles significantly inhibited the growth of P. aeruginosa. All these efforts resulted in inhibition obtained at a drug concentration and light intensity much lower than what is reported by the works of previous investigators. PMID- 26808217 TI - Diffuse Large B-cell lymphoma: Prognostic markers and their impact on therapy. AB - Diffuse large B-cell lymphoma (DLBCL) is the most common type of Non-Hodgkin lymphoma (NHL). DLBCL is clinically, pathologically and molecularly heterogeneous disease. Various clinical, pathological and molecular markers have been developed to characterize the disease. Based on these characterizations, new targeted agents are being investigated to optimize the treatment and improve the outcomes of DLBCL. Enhanced molecular understanding, invention of targeted agents and immunotherapy has opened the doors for improvement in the treatment of DLBCL. In this review, we will discuss various prognostic markers of DLBCL and their potential therapeutic implications. PMID- 26808218 TI - Validation of an LC-MS/MS method for the simultaneous quantification of dabigatran, rivaroxaban and apixaban in human plasma. AB - AIM: Novel oral anticoagulants are characterized by a wide therapeutic window, yet the determination of their plasma-drug concentrations may be useful in some clinical conditions. RESULTS: An LC-MS/MS method for the analysis of dabigatran, apixaban and rivaroxaban in human plasma has been successfully developed and validated. The analysis of plasma samples from patients given other concomitant drugs revealed no significant interference. By reanalysis of samples from patients on anticoagulant therapy, we found the percentage difference in results between the concentration of repeat and the original sample to be within the threshold limit of 20% in 60 of 63 specimens. CONCLUSION: The developed LC-MS/MS assay is easily applicable in the clinical management of patients on anticoagulation therapy. PMID- 26808219 TI - Both endoplasmic reticulum and mitochondrial pathways are involved in oligodendrocyte apoptosis induced by capsular hemorrhage. AB - OBJECTIVE: The white matter injury caused by intracerebral hemorrhage (ICH) includes demyelination and axonal injury. Oligodendrocyte apoptosis is reported to be involved in triggering demyelination. Experimental observations indicate that both endoplasmic reticulum and mitochondrial pathways could mediate cell apoptosis. The purpose of this study was to investigate the demyelination and the possible mechanisms in an autologous blood-injected rat model of internal capsule hemorrhage. METHODS: Transmission electron microscope was applied to examine the pathological changes of myelinated nerve fibers in internal capsule. Western blotting was used to detect the myelin basic protein (MBP) which was an important component of myelin sheath. Double immunofluorescence and Western blotting were used to determine the apoptosis and apoptotic pathways. The levels of caspase-12 (a representative protein of endoplasmic reticulum stress) and cytochrome c (an apoptosis factor released from mitochondria) were assessed in this study. RESULTS: Demyelination occurred on day 1, 3, and 7 after ICH onset. Myelin sheaths of internal capsule nerve fibers were swollen and broken down in ICH groups. MBP expression showed a downregulation after ICH with its minimum value occurred on day 7 post-ICH. Besides, neuron and oligodendrocyte apoptosis were observed at different time intervals post-ICH accompanied with an upregulated caspase-12 expression and enhanced cytochrome c release. CONCLUSIONS: These results suggested that oligodendrocyte and neuron apoptosis may contribute to the demyelination induced by internal capsule hemorrhage and oligodendrocyte apoptosis is positively mediated through both endoplasmic reticulum and mitochondrial pathways. PMID- 26808216 TI - Integrated Magneto-Electrochemical Sensor for Exosome Analysis. AB - Extracellular vesicles, including exosomes, are nanoscale membrane particles that carry molecular information on parental cells. They are being pursued as biomarkers of cancers that are difficult to detect or serially follow. Here we present a compact sensor technology for rapid, on-site exosome screening. The sensor is based on an integrated magneto-electrochemical assay: exosomes are immunomagnetically captured from patient samples and profiled through electrochemical reaction. By combining magnetic enrichment and enzymatic amplification, the approach enables (i) highly sensitive, cell-specific exosome detection and (ii) sensor miniaturization and scale-up for high-throughput measurements. As a proof-of-concept, we implemented a portable, eight-channel device and applied it to screen extracellular vesicles in plasma samples from ovarian cancer patients. The sensor allowed for the simultaneous profiling of multiple protein markers within an hour, outperforming conventional methods in assay sensitivity and speed. PMID- 26808220 TI - Downregulation of the spinal dorsal horn clock gene Per1 expression leads to mechanical hypersensitivity via c-jun N-terminal kinase and CCL2 production in mice. AB - Disturbances of circadian rhythm and dysregulation of clock gene expression are involved in the induction of various neurological disorder states, including chronic pain. However, the relationship between the CNS circadian-clock gene system and nociception remains poorly defined. Significant circadian oscillations of Period (Per1, Per2), Bmal1 and Cryptochrome 1 (Cry1) mRNA expression have been observed in the lumbar spinal dorsal horn of naive mice. The current study examined the expression of clock genes in the lumbar spinal dorsal horn of mice with neuropathic pain due to a partial sciatic nerve ligation (PSNL). Seven days after PSNL, the mice displayed a robust unilateral hind paw mechanical hypersensitivity. The normal circadian oscillations of Per1, Per2 and Cry1, but not Bmal1, mRNA expression were significantly suppressed in the ipsilateral lumbar spinal dorsal horn of PSNL mice 7days following surgery. The circadian expression of PER1 protein, in particular, was also significantly suppressed in the ipsilateral spinal dorsal horn of PSNL mice. Double-labeling immunohistochemistry revealed downregulation of PER1 in neurons and astrocytes, but not microglia. Knockdown of Per1 expression by intrathecal treatment with Per1 siRNA also induced mechanical hypersensitivity, phosphorylation of c-jun N terminal kinase (JNK) and the upregulation of chemokine (C-C motif) ligand 2 (CCL2) production in the lumbar spinal dorsal horn. Per1 siRNA-induced mechanical hypersensitivity was attenuated with intrathecal treatment of either the JNK inhibitor SP600125 or the selective CCL2 receptor (CCR2) antagonist RS504393, indicating that these intracellular messengers are crucial in mediating the mechanical hypersensitivity following the downregulation of PER1 expression. These results suggest that the downregulation of the spinal dorsal horn clock genes such as Per1 expressed could be crucial in the induction of neuropathic pain following peripheral nerve injury. Modulating clock gene Per1 expression could be a novel therapeutic strategy in alleviating neuropathic pain. PMID- 26808221 TI - Fyn kinase genetic ablation causes structural abnormalities in mature retina and defective Muller cell function. AB - Fyn kinase is widely expressed in neuronal and glial cells of the brain, where it exerts multiple functional roles that affect fundamental physiological processes. The aim of our study was to investigate the, so far unknown, functional role of Fyn in the retina. We report that Fyn is expressed, in vivo, in a subpopulation of Muller glia. We used a mouse model of Fyn genetic ablation and Muller-enriched primary cultures to demonstrate that Fyn deficiency induces morphological alterations in the mature retina, a reduction in the thickness of the outer and inner nuclear layers and alterations in postnatal Muller cell physiology. These include shortening of Muller cell processes, a decrease in cell proliferation, inactivation of the Akt signal transduction pathway, a reduced number of focal adhesions points and decreased adhesion of these cells to the ECM. As abnormalities in Muller cell physiology have been previously associated to a compromised retinal function we evaluated behavioral responses to visual stimulation. Our results associate Fyn deficiency with impaired visual optokinetic responses under scotopic and photopic light conditions. Our study reveals novel roles for Fyn kinase in retinal morphology and Muller cell physiology and suggests that Fyn is required for optimal visual processing. PMID- 26808222 TI - Relevance of progesterone receptor immunohistochemical staining to Oncotype DX recurrence score. AB - OBJECTIVE/BACKGROUND: Progesterone-receptor negativity (PR-) is predictive of adverse outcomes in estrogen receptor-positive (ER+) breast cancer. The Oncotype DX assay provides risk stratification for hormone receptor-positive (HR+) invasive breast cancer; however, the association of PR status and Oncotype DX recurrence scores (RSs) is less clear. METHODS: We designed an analysis to determine whether a significant difference exists in the RS for ER+/PR- tumors when compared with ER+/PR+ breast cancer. Three hundred and fifty patients with HR+ invasive breast cancer who underwent Oncotype DX testing at our institution from December 2006 to October 2013 were included. We also examined the concordance in the HR status reported by immunohistochemical (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. The data were analyzed by analysis of variance, F test, t test, and chi-square tests. Multivariate linear regression was used to determine significant predictors of Oncotype DX RS. RESULTS: A total of 301 patients had ER+/PR+ tumors and 47 patients had ER+/PR- tumors by IHC. PR- tumors had a significantly higher RS than PR+ tumors (24.7+/ 8.53 vs. 17.3+/-7.38; p<.001), predicting a greater 10-year risk of distant recurrence. Multivariate linear regression showed PR status and tumor grade to be significant predictors of Oncotype DX RS (p<.0001). A total of 284 patients had HR status reported by Oncotype DX assay. Concordance between IHC and RT-PCR was 99.3% for ER and 88.7% for PR. CONCLUSION: Our study shows that ER+/PR- breast cancer tumors are associated with a significantly higher Oncotype DX scores; this interprets into a higher risk of recurrence. Our data also show that the concordance between IHC and RT-PCR was 99.3% for ER and lower at 88.7% for PR. PMID- 26808223 TI - Biomarkers of Metabolic Syndrome: Biochemical Background and Clinical Significance. AB - Biomarkers of the metabolic syndrome are divided into four subgroups. Although dividing them in groups has some limitations, it can be used to draw some conclusions. In a first part, the dyslipidemias and markers of oxidative stress are discussed, while inflammatory markers and cardiometabolic biomarkers are reviewed in a second part. For most of them, the biochemical background and clinical significance are discussed, although here also a well-cut separation cannot always be made. Altered levels cannot always be claimed as the cause, risk, or consequence of the syndrome. Several factors are interrelated to each other and act in a concerted, antagonistic, synergistic, or modulating way. Most important conclusions are summarized at the end of every reviewed subgroup. Genetic biomarkers or influences of various food components on concentration levels are not included in this review article. PMID- 26808224 TI - The transfer of (137)Cs, Pu isotopes and (90)Sr to bird, bat and ground-dwelling small mammal species within the Chernobyl exclusion zone. AB - Protected species are the focus of many radiological environmental assessments. However, the lack of radioecological data for many protected species presents a significant international challenge. Furthermore, there are legislative restrictions on destructive sampling of protected species to obtain such data. Where data are not available, extrapolations are often made from 'similar' species but there has been little attempt to validate this approach. In this paper we present what, to our knowledge, is the first study purposefully designed to test the hypothesis that radioecological data for unprotected species can be used to estimate conservative radioecolgical parameters for protected species; conservatism being necessary to ensure that there is no significant impact. The study was conducted in the Chernobyl Exclusion Zone. Consequently, we are able to present data for Pu isotopes in terrestrial wildlife. There has been limited research on Pu transfer to terrestrial wildlife which contrasts with the need to assess radiation exposure of wildlife to Pu isotopes around many nuclear facilities internationally. Our results provide overall support for the hypothesis that data for unprotected species can be used to adequately assess the impacts for ionising radiation on protected species. This is demonstrated for a range of mammalian and avian species. However, we identify one case, the shrew, for which data from other ground-dwelling small mammals would not lead to an appropriately conservative assessment of radiation impact. This indicates the need to further test our hypothesis across a range of species and ecosystems, and/or ensure adequate conservatism within assessments. The data presented are of value to those trying to more accurately estimate the radiation dose to wildlife in the Chernobyl Exclusion Zone, helping to reduce the considerable uncertainty in studies reporting dose-effect relationships for wildlife. A video abstract for this paper is available from: http://bit.ly/1JesKPc. PMID- 26808225 TI - The pentavalent actinide solution chemistry in the environment. AB - With regard to environmental monitoring of certain nuclear facilities, pentavalent actinides, in particular neptunium and plutonium, play a key role, as the chief soluble, mobile forms of actinides. In the past five years, investigations carried out by hyphenating capillary electrophoresis to ICP-MS (CE ICP-MS) have allowed a number of hitherto unknown thermodynamic data to be determined for Np(V) and Pu(V) interactions with the chief environmentally abundant anions. For the first time, data were provided for Pu(V) interactions with carbonate, sulfate, oxalate, chloride, and nitrate ions, allowing the Np(V)/Pu(V) analogy to be verified experimentally. Knowledge of Np(V) chemistry, especially in carbonate, and sulfate media, was also refined. These CE-ICP-MS studies, combined with some earlier findings, have brought about a renewal in the knowledge of An(V) chemistry in solution. PMID- 26808226 TI - Porous Core-Shell Fe3C Embedded N-doped Carbon Nanofibers as an Effective Electrocatalysts for Oxygen Reduction Reaction. AB - The development of nonprecious-metal-based electrocatalysts with high oxygen reduction reaction (ORR) activity, low cost, and good durability in both alkaline and acidic media is very important for application of full cells. Herein, we developed a facile and economical strategy to obtain porous core-shell Fe3C embedded nitrogen-doped carbon nanofibers (Fe3C@NCNF-X, where X denotes pyrolysis temperature) by electrospinning of polyvinylidene fluoride (PVDF) and FeCl3 mixture, chemical vapor phase polymerization of pyrrole, and followed by pyrolysis of composite nanofibers at high temperatures. Note that the FeCl3 and polypyrrole acts as precursor for Fe3C core and N-doped carbon shell, respectively. Moreover, PVDF not only plays a role as carbon resources, but also provides porous structures due to hydrogen fluoride exposure originated from thermal decomposition of PVDF. The resultant Fe3C@NCNF-X catalysts, particularly Fe3C@NCNF-900, showed efficient electrocatalytic performance for ORR in both alkaline and acidic solutions, which are attributed to the synergistic effect between Fe3C and N-doped carbon as catalytic active sites, and carbon shell protects Fe3C from leaching out. In addition, the Fe3C@NCNF-X catalyst displayed a better long-term stability, free from methanol crossover and CO-poisoning effects than those of Pt/C, which is of great significance for the design and development of advanced electrocatalysts based on nonprecious metals. PMID- 26808228 TI - Modelling materials for solar fuel synthesis by artificial photosynthesis; predicting the optical, electronic and redox properties of photocatalysts. AB - In this mini-review, we discuss what insight computational modelling can provide into the working of photocatalysts for solar fuel synthesis and how calculations can be used to screen for new promising materials for photocatalytic water splitting and carbon dioxide reduction. We will extensively discuss the different relevant (material) properties and the computational approaches (DFT, TD-DFT, GW/BSE) available to model them. We illustrate this with examples from the literature, focussing on polymeric and nanoparticle photocatalysts. We finish with a perspective on the outstanding conceptual and computational challenges. PMID- 26808227 TI - On the different experimental manifestations of two-state 'induced-fit' binding of drugs to their cellular targets. AB - 'Induced-fit' binding of drugs to a target may lead to high affinity, selectivity and a long residence time, and this mechanism has been proposed to apply to many drugs with high clinical efficacy. It is a multistep process that initially involves the binding of a drug to its target to form a loose RL complex and a subsequent isomerization/conformational change to yield a tighter binding R'L state. Equations with the same mathematical form may also describe the binding of bivalent antibodies and related synthetic drugs. Based on a selected range of 'microscopic' rate constants and variables such as the ligand concentration and incubation time, we have simulated the experimental manifestations that may go along with induced-fit binding. Overall, they validate different experimental procedures that have been used over the years to identify such binding mechanisms. However, they also reveal that each of these manifestations only becomes perceptible at particular combinations of rate constants. The simulations also show that the durable nature of R'L and the propensity of R'L to be formed repeatedly before the ligand dissociates will increase the residence time. This review may help pharmacologists and medicinal chemists obtain preliminary indications for identifying an induced-fit mechanism. PMID- 26808229 TI - Epigenetic regulation of the expression of Il12 and Il23 and autoimmune inflammation by the deubiquitinase Trabid. AB - The proinflammatory cytokines interleukin 12 (IL-12) and IL-23 connect innate responses and adaptive immune responses and are also involved in autoimmune and inflammatory diseases. Here we describe an epigenetic mechanism for regulation of the genes encoding IL-12 (Il12a and Il12b; collectively called 'Il12' here) and IL-23 (Il23a and Il12b; collectively called 'Il23' here) involving the deubiquitinase Trabid. Deletion of Zranb1 (which encodes Trabid) in dendritic cells inhibited induction of the expression of Il12 and Il23 by Toll-like receptors (TLRs), which impaired the differentiation of inflammatory T cells and protected mice from autoimmune inflammation. Trabid facilitated TLR-induced histone modifications at the promoters of Il12 and Il23, which involved deubiqutination and stabilization of the histone demethylase Jmjd2d. Our findings highlight an epigenetic mechanism for the regulation of Il12 and Il23 and establish Trabid as an innate immunological regulator of inflammatory T cell responses. PMID- 26808231 TI - Analysis of infectious complications and timing for emergency liver transplantation in autoimmune acute liver failure. AB - BACKGROUND: Autoimmune hepatitis (AIH) is one of major etiologies of acute liver failure (ALF), and the survival rate without liver transplantation (LT) of patients with fulminant AIH is especially poor worldwide. We investigated the clinicopathological features of infectious complications in autoimmune ALF retrospectively and tried to determine when to continue corticosteroid (CS) treatment or abandon it for LT. METHODS: Twenty patients with autoimmune ALF, comprising five severe hepatitis, 13 fulminant hepatitis and two late onset hepatic failure, were analyzed. RESULTS: Corticosteroids were administered to 19 patients. Seventeen infectious complications were observed in 12 patients. The median (range) duration between the introduction of CS and onset of infection was 15 (10-41) days. There were no significant differences in clinicobiochemical features between patients with and without infection. Of 20 patients, eight (40%) recovered without LT, four (20%) received LT and eight (40%) died without LT. Dead or transplanted patients had more advanced liver failure on admission than recovered ones (P < 0.01). CONCLUSIONS: Two-week after the introduction of CS is a critical point for avoiding infectious complications. Therefore, we should have evaluated efficacy of CS and performed LT by then at the latest in case of failure to improve. PMID- 26808230 TI - Autophagy enforces functional integrity of regulatory T cells by coupling environmental cues and metabolic homeostasis. AB - Regulatory T (Treg) cells respond to immune and inflammatory signals to mediate immunosuppression, but how the functional integrity of Treg cells is maintained under activating environments is unclear. Here we show that autophagy is active in Treg cells and supports their lineage stability and survival fitness. Treg cell-specific deletion of Atg7 or Atg5, two essential genes in autophagy, leads to loss of Treg cells, greater tumor resistance and development of inflammatory disorders. Atg7-deficient Treg cells show increased apoptosis and readily lose expression of the transcription factor Foxp3, especially after activation. Mechanistically, autophagy deficiency upregulates metabolic regulators mTORC1 and c-Myc and glycolysis, which contribute to defective Treg function. Therefore, autophagy couples environmental signals and metabolic homeostasis to protect lineage and survival integrity of Treg cells in activating contexts. PMID- 26808232 TI - Persistence of Ebola virus in various body fluids during convalescence: evidence and implications for disease transmission and control. AB - The aim of this study was to review the current evidence regarding the persistence of Ebola virus (EBOV) in various body fluids during convalescence and discuss its implication on disease transmission and control. We conducted a systematic review and searched articles from Medline and EMBASE using key words. We included studies that examined the persistence of EBOV in various body fluids during the convalescent phase. Twelve studies examined the persistence of EBOV in body fluids, with around 800 specimens tested in total. Available evidence suggests that EBOV can persist in some body fluids after clinical recovery and clearance of virus from the blood. EBOV has been isolated from semen, aqueous humor, urine and breast milk 82, 63, 26 and 15 days after onset of illness, respectively. Viral RNA has been detectable in semen (day 272), aqueous humor (day 63), sweat (day 40), urine (day 30), vaginal secretions (day 33), conjunctival fluid (day 22), faeces (day 19) and breast milk (day 17). Given high case fatality and uncertainties around the transmission characteristics, patients should be considered potentially infectious for a period of time after immediate clinical recovery. Patients and their immediate contacts should be informed about these risks. Convalescent patients may need to abstain from sex for at least 9 months or should use condoms until their semen tests are negative. Breastfeeding should be avoided during the convalescent phase. There is a need for more research on persistence, and a uniform approach to infection control guidelines in convalescence. PMID- 26808233 TI - 2015 Pediatric Research Priorities in Prehospital Care. AB - BACKGROUND: Pediatric prehospital research has been limited, but work in this area is starting to increase particularly with the growth of pediatric-specific research endeavors. Given the increased interest in pediatric prehospital research, there is a need to identify specific research priorities that incorporate the perspective of prehospital providers and other emergency medical services (EMS) stakeholders. OBJECTIVES: To develop a list of specific research priorities that is relevant, specific, and important to the practice of pediatric prehospital care. METHODS: Three independent committees of EMS providers and researchers were recruited. Each committee developed a list of research topics. These topics were collated and used to initiate a modified Delphi process for developing consensus on a list of research priorities. Participants were the committee members. Topics approved by 80% were retained as research priorities. Topics that were rejected by more than 50% were eliminated. The remaining topics were modified and included on subsequent surveys. Each survey allowed respondents to add additional topics. The surveys were continued until all topics were either successfully retained or rejected and no new topics were suggested. RESULTS: Fifty topics were identified by the three independent committees. These topics were included on the initial electronic survey. There were 5 subsequent surveys. At the completion of the final survey a total of 29 research priorities were identified. These research priorities covered the following study areas: airway management, asthma, cardiac arrest, pain, patient-family interaction, resource utilization, seizure, sepsis, spinal immobilization, toxicology, trauma, training and competency, and vascular access. The research priorities were very specific. For example, under airway the priorities were: "identify the optimal device for effectively managing the airway in the prehospital setting" and "identify the optimal airway management device for specific disease processes." CONCLUSION: This project developed a list of relevant, specific, and important research priorities for pediatric prehospital care. Some similarities exist between this project and prior research agendas but this list represents a current, more specific research agenda and reflects the opinions of working EMS providers, researchers, and leaders. KEY WORDS: emergency medical technician; research; emergency medical services; priorities. PMID- 26808234 TI - Autobiographical memory specificity in response to verbal and pictorial cues in clinical depression. AB - BACKGROUND: Depressed individuals have been consistently shown to exhibit problems in accessing specific memories of events from their past and instead tend to retrieve categorical summaries of events. The majority of studies examining autobiographical memory changes associated with psychopathology have tended to use word cues, but only one study to date has used images (with PTSD patients). OBJECTIVE: to determine if using images to cue autobiographical memories would reduce the memory specificity deficit exhibited by patients with depression in comparison to healthy controls. METHODS: Twenty-five clinically depressed patients and twenty-five healthy controls were assessed on two versions of the autobiographical memory test; cued with emotional words and images. RESULTS: Depressed patients retrieved significantly fewer specific memories, and a greater number of categorical, than did the controls. Controls retrieved a greater proportion of specific memories to images compared to words, whereas depressed patients retrieved a similar proportion of specific memories to both images and words. LIMITATIONS: no information about the presence and severity of past trauma was collected. CONCLUSIONS: results suggest that the overgeneral memory style in depression generalises from verbal to pictorial cues. This is important because retrieval to images may provide a more ecologically valid test of everyday memory experiences than word-cued retrieval.. PMID- 26808235 TI - A multi-functional nanoplatform for tumor synergistic phototherapy. AB - Phototherapy, which mainly includes photothermal treatment (PTT) and photodynamic treatment (PDT), is a photo-initiated, noninvasive and effective approach for cancer treatment. The high accumulation of photosensitizers (PSs) in a targeted tumor is still a major challenge for efficient light conversion, to generate reactive oxygen species (ROS) and local hyperthermia. In this study, a simple and efficient hyaluronic acid (HA)-modified nanoplatform (HA-TiO2@MWCNTs) with high tumor-targeting ability, excellent phototherapy efficiency, low light-associated side effects and good water solubility was developed. It could be an effective carrier to load hematoporphyrin monomethyl ether (HMME), owing to the tubular conjugate structure. Apart from this, the as-prepared TiO2@MWCNTs nanocomposites could also be used as PSs for tumor PTT and PDT. Those results in vitro and in vivo showed that the anti-tumor effect of this system-mediated PTT/PDT were significantly better than those of single treatment manner. In addition, this drug delivery system could realize high ratio of drug loading, sustained drug release, prolonged circulation in vivo and active targeted accumulation in tumor. These results suggest that HA-TiO2@MWCNTs/HMME has high potential for tumor synergistic phototherapy as a smart theranostic nanoplatform. PMID- 26808236 TI - Particles and enzymes: Combining nanoscale zero valent iron and organochlorine respiring bacteria for the detoxification of chloroethane mixtures. AB - Nanoscale zero valent iron (nZVI) and organochlorine respiring bacteria (ORB) are two technologies used to detoxify chlorinated aliphatic hydrocarbons (CAHs). nZVI can rapidly detoxify high CAH concentrations, but is quickly oxidised and unable to degrade certain CAHs (e.g., 1,2-dichlorothane). In contrast, ORB can dechlorinate CAHs resistant to nZVI (e.g., 1,2-dichlorothane) but are inhibited by other CAHs of concern degradable by nZVI (e.g., chloroform and carbon tetrachloride). Combining the two was proposed as a unique treatment train to overcome each technology's shortcomings. In this study, this combined remedy was investigated using a mixture of 1,2-dichloroethane, degradable by ORB but not nZVI, and 1,1,2-trichloroethane, susceptible to both. Results indicated that nZVI rapidly dechlorinated 1,1,2-trichloroethane when supplied above 0.5 g/L, however ORB were inhibited and unable to dechlorinate 1,2-dichloroethane. pH increase and ionic species associated with nZVI did not significantly impact ORB, pinpointing Fe(0) particles as responsible for ORB inhibition. Below 0.05 g/L nZVI, ORB activity was stimulated. Results suggest that combining ORB and nZVI at appropriate doses can potentially treat a wider range of CAHs than each individual remedy. At field sites where nZVI was applied, it is likely that in situ nZVI concentrations were below the threshold of negative consequences. PMID- 26808237 TI - Simultaneous oxidation and adsorption of As(III) from water by cerium modified chitosan ultrafine nanobiosorbent. AB - Since most existing arsenic removal adsorbents are difficult to effectively remove arsenite (As(III)), an urgent need is to develop an efficient adsorbent for removing As(III) from contaminated water. In this study, a novel ultrafine nanobiosorbent of cerium modified chitosan (Ce-CNB) with simultaneous oxidation and adsorption As(III) performance has been successfully developed. The resulting Ce-CNB with or without As(III) adsorption was characterized by FTIR, XRD, SEM, EDS, TEM, EMI and XPS analysis. Batch of adsorption experiments were performed to investigate the effects of various conditions on the As(III) adsorption. The adsorption behaviors were well described by the Langmuir isotherm and the pseudo second-order kinetic model, with the maximum adsorption capacities of 57.5 mg g( 1). The adsorption mechanisms for As(III) were (i) formed monodentate and bidentate complexes between hydroxyl groups and arsenite; and (ii) partial As(III) oxidized to As(V) followed by simultaneously adsorbed on the surface of Ce-CNB. This novel nanocomposite can be reused while maintaining a high removal efficiency and can be applied to treat 5.8L of As(III)-polluted water with the effluent concentration lower than the World Health Organization standard, which suggests its great potential to remove As(III) from contaminated water. PMID- 26808238 TI - Synthesis of akageneite (beta-FeOOH)/reduced graphene oxide nanocomposites for oxidative decomposition of 2-chlorophenol by Fenton-like reaction. AB - In this work, the composite of reduced graphene oxide and akageneite (Ak/rGO) was synthesised by co-precipitating and reduction processes. The morphological and structural features of the synthesized composites (Ak/rGO) were characterized by XRD, SEM, BET, FTIR, Zeta potential and XPS. The results revealed that (1) beta FeOOH was successfully loaded on the reduced graphene oxide (rGO); (2) the presence of strong interfacial interactions (Fe-O-C bonds) between rGO and beta FeOOH was observed; (3) the reduction of graphene oxide may be inhabited in the formation process of beta-FeOOH, producing rGO sheets rather than rGO sphere. In the heterogeneous Fenton-like reaction, the degradation rate constants of 2 chlorophenol (2-CP) increased 2-5 times after the addition of rGO probably due to the Fe-O-C bond. The increase of the content of rGO could contribute to the removal of 2-CP, due to the synergy of catalysis and 2-CP adsorption towards Ak/rGO. In this study, the Ak/rGO composite has exhibited great potential and significant prospects for environmental application. PMID- 26808239 TI - Mechanistic understanding of reduced AgNP phytotoxicity induced by extracellular polymeric substances. AB - A knowledge gap concerning the potential effects of extracellular polymeric substances (EPS), a common organic material but highly variable in their composition of microbial origin, on the fate and phytotoxicity of silver nanoparticles (AgNP) still remains. A 48-h root elongation toxicity test showed that AgNP toxicity to wheat Triticum aestivum L. was dramatically alleviated by EPS isolated from Pseudomonas putida, as revealed by 7-59% increase in relative root elongation (RRE), 8-99% increase in root weight, 27-32% decrease in malondialdehyde (MDA) content and 11-43% decrease in H2O2 content compared to the treatment with AgNP in the absence of EPS. This was coincident with 7-69% decrease in root Ag concentrations. Our results showed that EPS could protect wheat seedlings from AgNP toxicity by reducing dissolved Ag concentration ([Ag]diss) and by forming AgNP-EPS complex. The FTIR spectra further showed that the amide, carboxyl, and phosphoryl functional groups of EPS were involved in binding with AgNP and/or Ag(+). All these processes worked simultaneously to reduce AgNP bioavailability, and subsequently mitigate AgNP toxicity. These findings highlight the importance of EPS in AgNP biogeochemistry in the terrestrial environment. EPS could be highly useful in developing strategies to counteract the phytotoxicty of metal-based nanoparticles in crops. PMID- 26808240 TI - The potential of the innovative SeMPAC process for enhancing the removal of recalcitrant organic micropollutants. AB - SeMPAC is an innovative process based on a membrane sequential batch reactor to which powdered activated carbon (PAC) is directly added. It was developed with the aim of obtaining a high quality effluent in terms of conventional pollutants and organic micropollutants (OMPs). High COD removal and nitrification efficiencies (>95%) were obtained already during the operation without PAC, although denitrification was enhanced by PAC addition. OMPs were followed in the solid and liquid matrixes so that biotransformation, sorption onto the sludge and adsorption onto the PAC could be assessed. Recalcitrant compounds, such as carbamazepine and diazepam, were readily removed only after PAC addition (>99%). Progressive saturation of PAC was observed, with increasing concentrations of OMPs in the solid phase. Removal efficiencies for recalcitrant compounds were used as indicators for new additions of PAC. An improvement in the moderately biodegradable OMPs removal was observed after PAC addition (e.g. fluoxetine, trimethoprim) which was attributed to the biofilm that grew onto the sorbent, as well as to adsorption onto PAC. PMID- 26808241 TI - Hazards of low dose flame-retardants (BDE-47 and BDE-32): Influence on transcriptome regulation and cell death in human liver cells. AB - We have evaluated the in vitro low dose hepatotoxic effects of two flame retardants (BDE-47 and BDE-32) in HepG2 cells. Both congeners declined the viability of cells in MTT and NRU cell viability assays. Higher level of intracellular reactive oxygen species (ROS) and dysfunction of mitochondrial membrane potential (DeltaPsim) were observed in the treated cells. Comet assay data confirmed the DNA damaging potential of both congeners. BDE-47 exposure results in the appearance of subG1 apoptotic peak (30.1%) at 100 nM, while BDE-32 arrested the cells in G2/M phase. Among the set of 84 genes, BDE-47 induces downregulation of majority of mRNA transcripts, whilst BDE-32 showed differential expression of transcripts in HepG2. The ultrastructural analysis revealed mitochondrial swelling and degeneration of cristae in BDE-47 and BDE-32 treated cells. Overall our data demonstrated the hepatotoxic potential of both congeners via alteration of vital cellular pathways. PMID- 26808242 TI - Bacteria capable of degrading anthracene, phenanthrene, and fluoranthene as revealed by DNA based stable-isotope probing in a forest soil. AB - Information on microorganisms possessing the ability to metabolize different polycyclic aromatic hydrocarbons (PAHs) in complex environments helps in understanding PAHs behavior in natural environment and developing bioremediation strategies. In the present study, stable-isotope probing (SIP) was applied to investigate degraders of PAHs in a forest soil with the addition of individually (13)C-labeled phenanthrene, anthracene, and fluoranthene. Three distinct phylotypes were identified as the active phenanthrene-, anthracene- and fluoranthene-degrading bacteria. The putative phenanthrene degraders were classified as belonging to the genus Sphingomona. For anthracene, bacteria of the genus Rhodanobacter were the putative degraders, and in the microcosm amended with fluoranthene, the putative degraders were identified as belonging to the phylum Acidobacteria. Our results from DNA-SIP are the first to directly link Rhodanobacter- and Acidobacteria-related bacteria with anthracene and fluoranthene degradation, respectively. The results also illustrate the specificity and diversity of three- and four-ring PAHs degraders in forest soil, contributes to our understanding on natural PAHs biodegradation processes, and also proves the feasibility and practicality of DNA-based SIP for linking functions with identity especially uncultured microorganisms in complex microbial biota. PMID- 26808243 TI - Magnetic CoFe2O4 nanoparticles supported on titanate nanotubes (CoFe2O4/TNTs) as a novel heterogeneous catalyst for peroxymonosulfate activation and degradation of organic pollutants. AB - Magnetic spinel ferrites, as heterogeneous catalysts to generate powerful radicals from peroxymonosulfate (PMS) for the degradation of organic pollutants, have received much attention in recent years due to the characteristic of environmental benefits. In this study, with titanate nanotubes (TNTs) as catalyst support, a novel CoFe2O4/TNTs hybrid was constructed by an impregnation calcination method. Characterization results revealed that TNTs support could promise small size and good dispersion of CoFe2O4 nanoparticles. Compared to the pure CoFe2O4, the as-prepared CoFe2O4/TNTs not only exhibited better performance in catalytic decomposition of Rhodamine B, but also realized higher total organic carbon removal and less cobalt leaching, which could be attributed to the enhanced catalytic ability from smaller CoFe2O4 nanoparticles and the unique ion exchange ability from TNTs support. Some influential factors, including reaction temperature, dosages of PMS and CoFe2O4/TNTs, and pH values were investigated and analyzed. Moreover, CoFe2O4/TNTs maintained its catalytic efficiency during the repeated batch experiments and also displayed functional advantages in the catalytic degradation of phenol. We believe the CoFe2O4/TNTs hybrid can be an efficient and green heterogeneous catalyst for the degradation of organic pollutants, and this study provides insights into the rational design and development of alternative catalysts for wastewater treatment. PMID- 26808244 TI - Ascorbic acid enhanced activation of oxygen by ferrous iron: A case of aerobic degradation of rhodamine B. AB - Molecular oxygen activation by ferrous ions (Fe(II)) in aqueous solution could generate reactive oxygen species (ROS) with high oxidation potential via reaction between Fe(II) and oxygen molecules (Fe(II)/air), however, ROS yielded in the Fe(II)/air process is insufficient for removal of organic pollutants due to the irreversible ferric ions (Fe(III)) accumulation. In this study, we demonstrate that ascorbic acid (AA) could enhance ROS generation via oxygen activation by ferrous irons (AA/Fe(II)/air) and thus improve the degradation of rhodamine (RhB) significantly. It was found that the first-order aerobic degradation rate of RhB in the AA/Fe(II)/air process in the presence of ascorbic acid is more than 4 times that of the Fe(II)/Air system without adding ascorbic acid. The presence of ascorbic acid could relieve the accumulation of Fe(III) by reductive accelerating the Fe(III)/Fe(II) cycles, as well as lower the redox potential of Fe(III)/Fe(II) through chelating effect, leading to enhanced ROS generation for promoting RhB degradation. This study not only sheds light on the effect of ascorbic acid on aerobic Fe(II) oxidation, but also provides a green method for effective remediation of organic pollutants. PMID- 26808245 TI - Selective removals of heavy metals (Pb(2+), Cu(2+), and Cd(2+)) from wastewater by gelation with alginate for effective metal recovery. AB - A novel method that uses the aqueous sodium alginate solution for direct gelation with metal ions is developed for effective removal and recovery of heavy metals from industrial wastewater. The experimental study was conducted on Pb(2+), Cu(2+), and Cd(2+) as the model heavy metals. The results show that gels can be formed rapidly between the metals and alginate in less than 10 min and the gelation rates fit well with the pseudo second-order kinetic model. The optimum dosing ratio of alginate to the metal ions was found to be between 2:1 and 3:1 for removing Pb(2+) and around 4:1 for removing Cu(2+) and Cd(2+) from wastewater, and the metal removal efficiency by gelation increased as the solution pH increased. Alginate exhibited a higher gelation affinity toward Pb(2+) than Cu(2+) and Cd(2+), which allowed a selective removal of Pb(2+) from the wastewater in the presence of Cu(2+) and Cd(2+) ions. Chemical analysis of the gels suggests that the gelation mainly occurred between the metal ions and the -COO(-) and -OH groups on alginate. By simple calcination of the metal-laden gels at 700 degrees C for 1 h, the heavy metals can be well recovered as valuable resources. The metals obtained after the thermal treatment are in the form of PbO, CuO, and CdO nanopowders with crystal sizes of around 150, 50, and 100 nm, respectively. PMID- 26808246 TI - Dechlorination and decomposition of chloroform induced by glow discharge plasma in an aqueous solution. AB - In this study, efficient dechlorination and decomposition of chloroform (CF) induced by glow discharge plasma (GDP) in contact with a sodium sulfate solution was investigated. Intermediate byproducts were determined by ionic chromatography and headspace gas chromatography, respectively. Results showed that CF can be effectively dechlorinated and decomposed under the action of GDP. Both removal and dechlorination of CF increased with increasing pH and with addition of hydroxyl radical scavengers to the solution. Addition of H2O2 to the solution slightly decreased the CF removal. Formic acid, oxalic acid and dichloromethane were determined as the major intermediate byproducts. Final products were carbon dioxide and hydrochloric acid. Hydrated electrons were the most likely active species responsible for initiation of the dechlorination, and hydroxyl radicals may be the ones for the oxidation of the organic intermediate byproducts. Hydrolyses of the chloromethyl radicals contributed much in the mineralization of the organic chlorine. Reaction mechanism was proposed based on the dechlorination kinetics and the distribution of intermediate byproducts. PMID- 26808247 TI - The emission of fluorine gas during incineration of fluoroborate residue. AB - The emission behaviors of wastes from fluorine chemical industry during incineration have raised concerns because multiple fluorine products might danger human health. In this study, fluorine emission from a two-stage incineration system during the combustion of fluoroborate residue was examined. In a TG-FTIR analysis BF3, SiF4 and HF were identified as the initial fluorine forms to be released, while fluorine gases of greenhouse effect such as CF4 and SF6 were not found. Below 700 degrees C, NaBF4 in the sample decomposed to generate BF3. Then part of BF3 reacted with SiO2 in the system to form SiF4 or hydrolyzed to HF. At higher temperatures, the NaF left in the sample was gradually hydrolyzed to form HF. A lab-scale two-stage tube furnace is established to simulate the typical two stage combustion chamber in China. Experimental tests proved that HF was the only fluorine gas in the flue gas, and emissions of BF3 and SiF4 can be negligible. Thermodynamic equilibrium model predicted that all SiF4 would be hydrolyzed at 1100 degrees C in the secondary-chamber, which agreed well with the experimental results. PMID- 26808248 TI - Treatment of acid rock drainage using a sulfate-reducing bioreactor with zero valent iron. AB - This study assessed the bioremediation of acid rock drainage (ARD) in flow through columns testing zero-valent iron (ZVI) for the first time as the sole exogenous electron donor to drive sulfate-reducing bacteria in permeable reactive barriers. Columns containing ZVI, limestone or a mixture of both materials were inoculated with an anaerobic mixed culture and fed a synthetic ARD containing sulfuric acid and heavy metals (initially copper, and later also cadmium and lead). ZVI significantly enhanced sulfate reduction and the heavy metals were extensively removed (>99.7%). Solid-phase analyses showed that heavy metals were precipitated with biogenic sulfide in the columns packed with ZVI. Excess sulfide was sequestered by iron, preventing the discharge of dissolved sulfide. In the absence of ZVI, heavy metals were also significantly removed (>99.8%) due to precipitation with hydroxide and carbonate ions released from the limestone. Vertical-profiles of heavy metals in the columns packing, at the end of the experiment, demonstrated that the ZVI columns still had excess capacity to remove heavy metals, while the capacity of the limestone control column was approaching saturation. The ZVI provided conditions that enhanced sulfate reduction and generated alkalinity. Collectively, the results demonstrate an innovative passive ARD remediation process using ZVI as sole electron-donor. PMID- 26808249 TI - The effects of adsorbing organic pollutants from super heavy oil wastewater by lignite activated coke. AB - The adsorption of organic pollutants from super heavy oil wastewater (SHOW) by lignite activated coke (LAC) was investigated. Specifically, the effects of LAC adsorption on pH, BOD5/COD(Cr)(B/C), and the main pollutants before and after adsorption were examined. The removed organic pollutants were characterized by Fourier transform infrared spectroscopy (FTIR), Boehm titrations, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography with organic carbon detection (LC-OCD). FTIR spectra indicated that organic pollutants containing -COOH and -NH2 functional groups were adsorbed from the SHOW. Boehm titrations further demonstrated that carboxyl, phenolic hydroxyl, and lactonic groups on the surface of the LAC increased. GC-MS showed that the removed main organic compounds are difficult to be degraded or extremely toxics to aquatic organisms. According to the results of LC-OCD, 30.37 mg/L of dissolved organic carbons were removed by LAC adsorption. Among these, hydrophobic organic contaminants accounted for 25.03 mg/L. Furthermore, LAC adsorption was found to increase pH and B/C ratio of the SHOW. The mechanisms of adsorption were found to involve between the hydrogen bonding and the functional groups of carboxylic, phenolic, and lactonic on the LAC surface. In summary, all these results demonstrated that LAC adsorption can remove bio-refractory DOCs, which is beneficial for biodegradation. PMID- 26808250 TI - Numerical analysis of thermal decomposition for RDX, TNT, and Composition B. AB - Demilitarization of waste explosives on a commercial scale has become an important issue in many countries, and this has created a need for research in this area. TNT, RDX and Composition B have been used as military explosives, and they are very sensitive to thermal shock. For the safe waste treatment of these high-energy and highly sensitive explosives, the most plausible candidate suggested has been thermal decomposition in a rotary kiln. This research examines the safe treatment of waste TNT, RDX and Composition B in a rotary kiln type incinerator with regard to suitable operating conditions. Thermal decomposition in this study includes melting, 3 condensed phase reactions in the liquid phase and 263 gas phase reactions. Rigorous mathematical modeling and dynamic simulation for thermal decomposition were carried out for analysis of dynamic behavior in the reactor. The results showed time transient changes of the temperature, components and mass of the explosives and comparisons were made for the 3 explosives. It was concluded that waste explosives subject to heat supplied by hot air at 523.15K were incinerated safely without any thermal detonation. PMID- 26808251 TI - Soil as an archive of coal-fired power plant mercury deposition. AB - Mercury pollution is a global environmental problem that has serious implications for human health. One of the most important sources of anthropogenic mercury emissions are coal-burning power plants. Hg accumulations in soil are associated with their atmospheric deposition. Our study provides the first assessment of soil Hg on the entire Spanish surface obtained from one sampling protocol. Hg spatial distribution was analysed with topsoil samples taken from 4000 locations in a regular sampling grid. The other aim was to use geostatistical techniques to verify the extent of soil contamination by Hg and to evaluate presumed Hg enrichment near the seven Spanish power plants with installed capacity above 1000 MW. The Hg concentration in Spanish soil fell within the range of 1-7564 MUg kg( 1) (mean 67.2) and 50% of the samples had a concentration below 37 MUg kg(-1). Evidence for human activity was found near all the coal-fired power plants, which reflects that metals have accumulated in the basin over many years. Values over 1000 MUg kg(-1) have been found in soils in the vicinity of the Abono, Soto de Ribera and Castellon power plants. However, soil Hg enrichment was detectable only close to the emission source, within an approximate range of only 15 km from the power plants. We associated this effect with airborne emissions and subsequent depositions as the potential distance through fly ash deposition. Hg associated with particles of ash tends to be deposited near coal combustion sources. PMID- 26808252 TI - Mitochondrial dysfunction induced by ultra-small silver nanoclusters with a distinct toxic mechanism. AB - As noble metal nanoclusters (NCs) are widely employed in nanotechnology, their potential threats to human and environment are relatively less understood. Herein, the biological effects of ultra-small silver NCs coated by bovine serum albumin (BSA) (Ag-BSA NCs) on isolated rat liver mitochondria were investigated by testing mitochondrial swelling, membrane permeability, ROS generation, lipid peroxidation and respiration. It was found that Ag-BSA NCs induced mitochondrial dysfunction via synergistic effects of two different ways: (1) inducing mitochondrial membrane permeability transition (MPT) by interacting with the phospholipid bilayer of the mitochondrial membrane (not with specific MPT pore proteins); (2) damaging mitochondrial respiration by the generation of reactive oxygen species (ROS). As far as we know, this is the first report on the biological effects of ultra-small size nanoparticles (~2 nm) at the sub-cellular level, which provides significant insights into the potential risks brought by the applications of NCs. It would inspire us to evaluate the potential threats of nanomaterials more comprehensively, even though they showed no obvious toxicity to cells or in vivo animal models. Noteworthy, a distinct toxic mechanism to mitochondria caused by Ag-BSA NCs was proposed and elucidated. PMID- 26808253 TI - Antifungal activity of rimocidin and a new rimocidin derivative BU16 produced by Streptomyces mauvecolor BU16 and their effects on pepper anthracnose. AB - AIMS: The objective of this study was to explore antifungal metabolites targeting fungal cell envelope and to evaluate the control efficacy against anthracnose development in pepper plants. METHODS AND RESULTS: A natural product library comprising 3000 microbial culture extracts was screened via an adenylate kinase (AK)-based cell lysis assay to detect antifungal metabolites targeting the cell envelope of plant-pathogenic fungi. The culture extract of Streptomyces mauvecolor strain BU16 displayed potent AK-releasing activity. Rimocidin and a new rimocidin derivative, BU16, were identified from the extract as active constituents. BU16 is a tetraene macrolide containing a six-membered hemiketal ring with an ethyl group side chain instead of the propyl group in rimocidin. Rimocidin and BU16 showed broad-spectrum antifungal activity against various plant-pathogenic fungi and demonstrated potent control efficacy against anthracnose development in pepper plants. CONCLUSIONS: Antifungal metabolites produced by S. mauvecolor strain BU16 were identified to be rimocidin and BU16. The compounds displayed potent control efficacy against pepper anthracnose. SIGNIFICANCE AND IMPACT OF THE STUDY: Rimocidin and BU16 would be active ingredients of disease control agents disrupting cell envelope of plant pathogenic fungi. The structure and antifungal activity of rimocidin derivative BU16 is first described in this study. PMID- 26808254 TI - Assessment of rehabilitation needs in colorectal cancer treatment: Results from a mixed audit and qualitative study in Denmark. AB - Background Systematic assessments of cancer patients' rehabilitation needs are a prerequisite for devising appropriate survivorship programs. Little is known about the fit between needs assessment outlined in national rehabilitation policies and clinical practice. This study aimed to explore clinical practices related to identification and documentation of rehabilitation needs among patients with colorectal cancer at Danish hospitals. Material and methods A retrospective clinical audit was conducted utilizing data from patient files randomly selected at surgical and oncology hospital departments treating colorectal cancer patients. Forty patients were included, 10 from each department. Semi-structured interviews were carried out among clinical nurse specialists. Audit data was analyzed using descriptive statistics, qualitative data using thematic analysis. Results Documentation of physical, psychological and social rehabilitation needs initially and at end of treatment was evident in 10% (n = 2) of surgical patient trajectories and 35% (n = 7) of oncology trajectories. Physical rehabilitation needs were documented among 90% (n = 36) of all patients. Referral to municipal rehabilitation services was documented among 5% (n = 2) of all patients. Assessments at surgical departments were shaped by the inherent continuous assessment of rehabilitation needs within standardized fast-track colorectal cancer surgery. In contrast, the implementation of locally developed assessment tools inspired by the distress thermometer (DT) in oncology departments was challenged by a lack of competencies and funding, impeding integration of data into patient files. Conclusion Consensus must be reached on how to ensure more systematic, comprehensive assessments of rehabilitation needs throughout clinical cancer care. Fast-track surgery ensures systematic documentation of physical needs, but the lack of inclusion of data collected by the DT in oncological departments questions the efficacy of assessment tools and points to a need for distinguishing between surgical and oncological settings in national rehabilitation policies. PMID- 26808255 TI - Pharmacokinetics and Pulmonary Distribution of Clarithromycin and Rifampicin after Concomitant and Consecutive Administration in Foals. AB - Drug interactions often result from multiple pharmacokinetic changes, such as after rifampicin (RIF) and clarithromycin (CLA) in the treatment of abscessing lung diseases. Comedication of RIF may interact with CLA disposition by either induction of presystemic elimination processes and/or inhibition of uptake mechanisms because it regulates gene transcription and modulates function of various CYP enzymes, multidrug efflux and uptake transporters for which CLA is a substrate. To distinguish the transcriptional changes from the modulating interaction components upon CLA absorption and pulmonary distribution, we initiated a repeated-dose study in 12 healthy foals with CLA (7.5 mg/kg, p.o., b.i.d.) in comedication with RIF (10 mg/kg, p.o., b.i.d.) given either concomitantly with CLA or consecutively 4 h after CLA. Affinity of CLA to human P gp, MRP2, and MRP3 and to OCT1, OCT3, and PEPT1 was measured using Sf9-derived inside-out membrane vesicles and transfected HEK293 cells, respectively. ABCB1 (P gp) induction by RIF and affinity of CLA to equine P-gp were studied using primary equine hepatocytes. Absolute bioavailability of CLA was reduced from ~40% to below 5% after comedication of RIF in both schedules of administration, and Tmax occurred ~2-3 h earlier. The loss of bioavailability was not associated with increased 14-hydroxyclarithromycin (14-OH-CLA) exposure. After consecutive dosing, absolute bioavailability and pulmonary penetration of CLA increased ~2 fold compared to concomitant use. In vitro, CLA showed affinity to human and equine P-gp. Expression of ABCB1 mRNA was upregulated by RIF in 7 of 8 duodenal biopsy specimens and in primary equine hepatocytes. In conclusion, the major undesired influence of RIF on oral absorption and pulmonary distribution of CLA is associated with induction of intestinal P-gp. Consecutive administration to avoid competition with its intestinal uptake transport results in significantly, although not clinically relevant, improved systemic exposure. PMID- 26808256 TI - Sitagliptin and other 'gliptins'--why prescribe them? AB - INTRODUCTION: In 2008, the Federal Drug Administration (FDA) required all new glucose-lowering therapies to show cardiovascular safety, and this applies to the dipeptidyl peptidase (DPP)-4 inhibitors ('gliptins'). At present, there is contradictory evidence on whether the gliptins increase hospitalizations for heart failure. AREAS COVERED: This is an evaluation of the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) in high risk cardiovascular subjects with type 2 diabetes [1]. TECOS demonstrated non-inferiority for sitagliptin over placebo for the primary outcome, which was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. There was no difference in the rate of hospitalization for heart failure between sitagliptin and placebo. EXPERT OPINION: Despite the results of TECOS, debate over the effects of sitagliptin on the rates of hospitalizations for heart failure continues with some recent studies suggesting increased rates. Recently, empagliflozin (an inhibitor of sodium-glucose cotransporter 2) has been shown to reduce cardiovascular outcomes in subjects with type 2 diabetes, including the rates of hospitalization for heart failure. In our opinion, these positive findings with empagliflozin suggest that it should be prescribed in preference to the gliptins, including sitagliptin, unless any positive cardiovascular outcomes are reported for the gliptins. PMID- 26808257 TI - Impact of Widespread Cervical Cancer Screening: Number of Cancers Prevented and Changes in Race-specific Incidence. AB - OBJECTIVES: With recent approval of standalone HPV testing and increasing uptake of HPV vaccination, some have postulated that we are moving toward a "post-Pap" era of cervical cancer prevention. However, the total number cases that have been prevented by Pap smear screening as well as its impact on racial disparities are unknown. METHODS: We estimated national cervical cancer incidence from 1976 to 2009 using the Surveillance, Epidemiology, and End Result database. Screening data were obtained from the literature and National Cancer Institute Progress Reports. We examined early, late, and race-specific trends in cancer incidence, and calculated the estimated number of cancers prevented over the past 3 decades. RESULTS: From 1976 to 2009, there was a significant decrease in the incidence of early-stage cervical cancer, from 9.8 to 4.9 cases per 100,000 women (P<0.001). Late-stage disease incidence also decreased, from 5.3 to 3.7 cases per 100,000 women (P<0.001). The incidence among black women decreased from 26.9 to 9.7 cases per 100,000 women (P<0.001), a greater decline compared with that of white women and women of other races. After adjusting for "prescreening era" rates of cervical cancer, we estimate that Pap smears were associated with a reduction of between 105,000 and 492,000 cases of cervical cancer over the past 3 decades in the United States. CONCLUSIONS: A large number of early-stage and late-stage cervical cancers were prevented and racial disparity in cancer rates were reduced during an era of widespread Pap smear screening. PMID- 26808258 TI - Late Effects After Radiotherapy for Childhood Low-grade Glioma. AB - OBJECTIVES: This single-institution report describes long-term disease control and late effects in pediatric patients with low-grade glioma (LGG) following radiotherapy (RT). MATERIALS AND METHODS: Twenty-nine pediatric patients with LGG were treated with photon-based RT from 1970 to 2004 (mean age at time of RT, 9.8 y; range, 0.6 to 19 y). One patient underwent gross total resection, 25 underwent subtotal resection or biopsy, and 3 were treated based on radiographic characteristics alone. Three patients underwent chemotherapy before RT. The median RT dose was 54 Gy (range, 40 to 55 Gy). RESULTS: The median follow-up was 17.8 years (range, 1.6 to 36.8 y) for all patients and 19.9 years (range, 1.6 to 36.8 y) for all living patients. The 5-, 10-, and 20-year local control and progression-free survival rates were equivalent at 82%, 74%, and 63%, respectively. The 5-, 10-, and 20-year cause-specific survival and overall survival rates were equivalent at 89%, 85%, and 58%, respectively. On univariate analysis, age below 4 years during treatment was associated with significantly inferior local control (P=0.0067), cause-specific survival (P=0.0021), and overall survival (P=0.0021). Of the 23 survivors analyzed for late toxicity, 15 (65%) developed grade 3+ toxicity. The most common Common Terminology Criteria for Adverse Events grade 3 toxicity (30% of survivors) was serious cognitive disability. Four patients (14%) died secondary to treatment complications, all occurring over a decade after completing RT. CONCLUSIONS: Over half of children diagnosed with LGG survive >20 years after RT; this report reveals the chronicity of toxicity beyond the typically reported follow-up. Our findings inform the therapeutic ratio of RT in this disease and may help guide late-effect screening recommendations. PMID- 26808259 TI - Smoking Decreases Survival in Locally Advanced Cervical Cancer Treated With Radiation. AB - PURPOSE: To study the prevalence and effect of smoking on cervical cancer recurrence and mortality in patients undergoing definitive treatment with radiation. MATERIALS AND METHODS: Between July 2007 and September 2013, 96 locally advanced cervical cancer patients received definitive radiation or chemoradiation followed by brachytherapy. Smoking status was obtained from prospective intake questionnaires and quantified by pack-years. Pelvic control (PC), disease-free survival (DFS), and overall survival (OS) were analyzed by multivariable Cox proportional hazards models. RESULTS: Smoking history included 51 (53.1%) nonsmokers, 45 active smokers, and former smokers: 20 (20.8%) with 1 to 20 pack-years and 25 (26%) with 21+ pack-years. With a median follow-up of 2 years on univariate analysis, the impact of 1 to 20 pack-years on PC, DFS, and OS relative to nonsmokers was hazard ratio (HR) 4.29 (95% confidence interval [CI], 1.36-14.1; P=0.014), 4.99 (95% CI, 1.21-22.4; P=0.027), and 4.77 (95% CI, 1.34 17.8; P=0.017), respectively. For patients with 21+ pack-years, the impact on PC, DFS, and OS was HR=6.13 (95% CI, 2.29-18.6; P<0.001), 7.24 (95% CI, 2.28-29.1; P=0.001), and 4.21 (95% CI, 1.26-15.4; P=0.02). On multivariate analysis, there remained a significant difference of 1 to 20 pack-years smoking history on OS relative to nonsmokers, HR=4.68 (95% CI, 1.02-29; P=0.047). For patients with 21+ pack-years smoking history, there continued to be a negative impact on PC and DFS, HR=5.66 (95% CI, 1.7-22.18; P=0.004) and HR=6.89 (95% CI, 1.54-42; P=0.011), respectively. CONCLUSIONS: Former and active tobacco smoking during radiation therapy for cervical cancer is associated with unfavorable PC, DFS, and OS outcomes. The increased number of smoking pack-years conferred a worse outcome effect in those treated with radiation. PMID- 26808260 TI - Cytoplasmic Ubiquitin-Specific Protease 19 (USP19) Modulates Aggregation of Polyglutamine-Expanded Ataxin-3 and Huntingtin through the HSP90 Chaperone. AB - Ubiquitin-specific protease 19 (USP19) is one of the deubiquitinating enzymes (DUBs) involved in regulating the ubiquitination status of substrate proteins. There are two major isoforms of USP19 with distinct C-termini; the USP19_a isoform has a transmembrane domain for anchoring to the endoplasmic reticulum, while USP19_b contains an EEVD motif. Here, we report that the cytoplasmic isoform USP19_b up-regulates the protein levels of the polyglutamine (polyQ) containing proteins, ataxin-3 (Atx3) and huntingtin (Htt), and thus promotes aggregation of their polyQ-expanded species in cell models. Our data demonstrate that USP19_b may orchestrate the stability, aggregation and degradation of the polyQ-expanded proteins through the heat shock protein 90 (HSP90) chaperone system. USP19_b directly interacts with HSP90 through its N-terminal CS (CHORD and SGT1)/P23 domains. In conjunction with HSP90, the cytoplasmic USP19 may play a key role in triage decision for the disease-related polyQ-expanded substrates, suggesting a function of USP19 in quality control of misfolded proteins by regulating their protein levels. PMID- 26808262 TI - Durable PROX catalyst based on gold nanoparticles and hydrophobic silica. AB - 3 nm gold nanoparticles obtained by direct chemical reduction of AuPPh3Cl in the presence of hydrophobic silica are highly active and selective over a prolonged period of time in the low temperature oxidation of CO in the presence of hydrogen. PMID- 26808261 TI - Social Norms of Cooperation in Small-Scale Societies. AB - Indirect reciprocity, besides providing a convenient framework to address the evolution of moral systems, offers a simple and plausible explanation for the prevalence of cooperation among unrelated individuals. By helping someone, an individual may increase her/his reputation, which may change the pre-disposition of others to help her/him in the future. This, however, depends on what is reckoned as a good or a bad action, i.e., on the adopted social norm responsible for raising or damaging a reputation. In particular, it remains an open question which social norms are able to foster cooperation in small-scale societies, while enduring the wide plethora of stochastic affects inherent to finite populations. Here we address this problem by studying the stochastic dynamics of cooperation under distinct social norms, showing that the leading norms capable of promoting cooperation depend on the community size. However, only a single norm systematically leads to the highest cooperative standards in small communities. That simple norm dictates that only whoever cooperates with good individuals, and defects against bad ones, deserves a good reputation, a pattern that proves robust to errors, mutations and variations in the intensity of selection. PMID- 26808263 TI - Differentiation between dogs with thrombosis and normal dogs using the overall hemostasis potential assay. AB - OBJECTIVE: To determine whether the overall hemostasis potential (OHP) and calibrated automated thrombogram (CAT) were significantly different between dogs with thrombosis and normal dogs. ANIMALS: Ten dogs with clinical evidence of thromboembolic disease had both OHP and CAT performed. Forty healthy control dogs had OHP performed, and 23 of these also had CAT performed. MEASUREMENTS AND MAIN RESULTS: Dogs with thrombosis had significantly higher OHP (P = 0.003), overall coagulation potential (P = 0.0001), and maximum optical density (Max OD, P < 0.0001) than normal dogs, and a significantly longer delay in the start of clot formation (P = 0.01). Max OD was higher than established reference intervals in 80% of the dogs with thrombosis. Using the CAT assay, dogs with thrombosis had a significantly longer lag time than normal dogs (P < 0.001). Plasma fibrinogen concentration correlated positively with overall coagulation potential, OHP, Max OD, and the slope of the OHP curve (P < 0.05), and was increased in 90% of dogs with thrombosis. CONCLUSIONS: The OHP assay findings were significantly different between normal dogs and those with thrombosis. CAT did not detect any significant differences between these populations of dogs, other than the lag time of the assay. PMID- 26808264 TI - Is early starvation beneficial for the critically ill patient? AB - PURPOSE OF REVIEW: Anorexia is a preserved evolutionally response that may be beneficial during acute illness. Yet current clinical practice guidelines recommend early and targeted enteral nutritional support. However, the optimal timing of the initiation of enteral nutrition and the caloric and protein requirements of critically ill patients is controversial. RECENT FINDINGS: Starvation promotes autophagy and this may play a key role in promoting host defenses and the immune response to intracellular pathogens. Because of the perceived benefits of early enteral nutrition and the lack of clinical equipoise, randomized controlled trials comparing short-term starvation to targeted normocaloric enteral nutrition have until recently not been performed. The results of the recently reported PYTHON trial (Pancreatitis, Very Early Compared with Selective Delayed Start of Enteral Feeding) dispel the notion that short term starvation is harmful. Furthermore, six recent randomized controlled trials that compared trophic and permissive underfeeding to normocaloric goals, failed to demonstrate any outcome benefit from the more aggressive approach. In addition, recent evidence suggests that intermittent enteral nutation may be preferable to continuous tube feeding. SUMMARY: Limiting nutrient intake during the first 48-72 h of acute illness may be beneficial; in those patients who are unable to resume an oral diet after this time period intermittent enteral nutrition targeting 20-25 cal/kg/day is recommended. PMID- 26808265 TI - Short update on docosapentaenoic acid: a bioactive long-chain n-3 fatty acid. AB - PURPOSE OF REVIEW: Docosapentaenoic acid (DPA) is a long-chain n-3 polyunsaturated fatty acid that is intermediary between eicosapentaenoic acid and docosahexaenoic acid in the n-3 synthesis pathway. DPA is part of our normal diet through fish and lean red meat. In recent years, DPA has received increasing attention as an important bioactive fatty acid in light of its potential beneficial health effects, which include anti-inflammatory actions, antiplatelet aggregation, and improved plasma lipid prolife. This review provides a short summary of the most recent research on DPA. RECENT FINDINGS: In this review, we report on the latest association data as well as data generated from in-vitro and in-vivo studies on DPA and cardiovascular health, mental health, inflammation, and cancer. We also report on the newly identified DPA metabolites and their effects on exacerbation of inflammation in animal models. SUMMARY: Although there is a growing body of evidence supporting DPA's role as an important bioactive fatty acid, there is a need for more 'cause and effect studies', clinical trials and studies which can reveal whether DPA plays separate roles to those identified for eicosapentaenoic acid and docosahexaenoic acid. PMID- 26808266 TI - Assessment of skeletal muscle mass in critically ill patients: considerations for the utility of computed tomography imaging and ultrasonography. AB - PURPOSE OF REVIEW: Low muscularity and skeletal muscle atrophy are commonly exhibited in critically ill patients and have major implications on patient outcomes. Typically, in the ICU, body composition is assessed through anthropometrics or bioelectrical impedance analysis, but these modalities cannot specifically quantify skeletal muscle; thus, we evaluate the merits and challenges of using computed tomography (CT) and ultrasonography to specifically measure skeletal muscle in the ICU. RECENT FINDINGS: CT-based cut points have been used to identify critically ill patients with low muscle mass, and low muscularity associates with poor clinical outcomes and function. Ultrasonography is emerging as a useful tool to quantify skeletal muscle loss and degradation in architecture, as well as prospectively track changes in these parameters over time. Rates of muscle atrophy and changes in muscle architecture has been quantified by ultrasonography and associated with poor clinical outcomes, but identification of critically ill patients with low muscularity is still in its infancy. SUMMARY: CT imaging and ultrasonography require additional comprehensive validations against accurate measures of whole body muscle mass. As these validations begin to emerge, there will be a need to translate this knowledge into a simple tool that clinicians can apply as part of routine care. PMID- 26808267 TI - Nutritional needs for the critically ill in relation to inflammation. AB - PURPOSE OF REVIEW: This review focuses on nutritional needs in critically ill patients. The inflammation corresponding to acute stress is highlighted. Simultaneously, we try to avoid limiting the perspective to only the acute phase. RECENT FINDINGS: During the last year, a number of important studies on nutritional needs in the critically ill have been published, including large randomized controlled trials. In particular studies addressing the needs for energy and proteins in the critically ill have imparted new knowledge in this field. However, there are few studies concerning the rehabilitation phase after critical illness. SUMMARY: Although the recent findings and publications contribute to a more nuanced understanding of nutrition during critical illness, the implications for clinical practice are not in discord with the current recommendations of guidelines. PMID- 26808269 TI - Unexpected Interactions of the Cyanobacterial Metallothionein SmtA with Uranium. AB - Molecules for remediating or recovering uranium from contaminated environmental resources are of high current interest, with protein-based ligands coming into focus recently. Metallothioneins either bind or redox-silence a range of heavy metals, conferring protection against metal stress in many organisms. Here, we report that the cyanobacterial metallothionein SmtA competes with carbonate for uranyl binding, leading to formation of heterometallic (UO2)(n)Zn4SmtA species, without thiol oxidation, zinc loss, or compromising secondary or tertiary structure of SmtA. In turn, only metalated and folded SmtA species were found to be capable of uranyl binding. (1)H NMR studies and molecular modeling identified Glu34/Asp38 and Glu12/C-terminus as likely adventitious, but surprisingly strong, bidentate binding sites. While it is unlikely that these interactions correspond to an evolved biological function of this metallothionein, their occurrence may offer new possibilities for designing novel multipurpose bacterial metallothioneins with dual ability to sequester both soft metal ions including Cu(+), Zn(2+), Cd(2+), Hg(2+), and Pb(2+) and hard, high-oxidation state heavy metals such as U(VI). The concomitant protection from the chemical toxicity of uranium may be valuable for the development of bacterial strains for bio remediation. PMID- 26808268 TI - Arginine- and Polyamine-Induced Lactic Acid Resistance in Neisseria gonorrhoeae. AB - Microbe-derived lactic acid protects women from pathogens in their genital tract. The purpose of this study was to determine lactic acid susceptibility of Neisseria gonorrhoeae, and identify potential acid resistance mechanisms present in this pathogen. Tested in vitro, lactic acid killed all 10 gonococcal strains analyzed in a low pH-dependent manner. Full inactivation occurred at pH 4.5. At low pH, lactic acid treatment resulted in the entry of the DNA-binding fluorochrome propidium iodide into the microbial cells, suggesting that hydrogen ions from lactic acid compromise the integrity of the bacterial cell wall/membrane. Most likely, hydrogen ions also inactivate intracellular proteins since arginine rendered significant protection against lactic acid presumably through action of the gonococcal arginine decarboxylase, an enzyme located in the bacterial cytoplasm. Surprisingly, arginine also lessened lactic acid-mediated cell wall/membrane disruption. This effect is probably mediated by agmatine, a triamine product of arginine decarboxylase, since agmatine demonstrated a stronger protective effect on GC than arginine at equal molar concentration. In addition to agmatine, diamines cadaverine and putrescine, which are generated by bacterial vaginosis-associated microbes, also induced significant resistance to lactic acid-mediated GC killing and cell wall/membrane disruption. These findings suggest that the arginine-rich semen protects gonococci through both neutralization-dependent and independent mechanisms, whereas polyamine-induced acid resistance contributes to the increased risk of gonorrhea in women with bacterial vaginosis. PMID- 26808270 TI - Z-Score-Based Modularity for Community Detection in Networks. AB - Identifying community structure in networks is an issue of particular interest in network science. The modularity introduced by Newman and Girvan is the most popular quality function for community detection in networks. In this study, we identify a problem in the concept of modularity and suggest a solution to overcome this problem. Specifically, we obtain a new quality function for community detection. We refer to the function as Z-modularity because it measures the Z-score of a given partition with respect to the fraction of the number of edges within communities. Our theoretical analysis shows that Z-modularity mitigates the resolution limit of the original modularity in certain cases. Computational experiments using both artificial networks and well-known real world networks demonstrate the validity and reliability of the proposed quality function. PMID- 26808271 TI - Pollen Organ Telangiopsis sp. of Late Devonian Seed Plant and Associated Vegetative Frond. AB - Pollen organ Telangiopsis sp., associated with but not attached to vegetative fronds, has been collected from the Upper Devonian (Famennian) Wutong Formation, Dongzhi County, Anhui Province, China. Fertile axes with terminal pollen organs are dichotomous for 2-4 times and may be proximally attached by fragmentary pinnules. Pollen organs are synangiate and borne on the top of a short stalk. Synangia are radial in symmetry and each consists of 4-8 elongate microsporangia fused at base. Microsporangia have a longitudinal dehiscence line and show a tapered apex. The associated stem is spiny and bears a vegetative frond which bifurcates once at the basalmost part. Frond rachises possess one order of pinna arranged alternately. Pinnules are borne alternately, planate, highly dissected, and equally dichotomous for 2-3 times. Comparisons among Late Devonian seed plants recognize several branching patterns in the fertile fronds/axes bearing terminal pollen organs. Telangiopsis sp. reinforces that the Late Devonian pollen organs are synangiate usually with basally fused microsporangia. It is suggested that the evolutionary divergence of radial and bilateral symmetries of pollen organs may have occurred in the Famennian, when the earliest seed plants evolved planate and sometimes laminate pinnules. PMID- 26808272 TI - Bias in Peripheral Depression Biomarkers. AB - BACKGROUND: To aid in the differentiation of individuals with major depressive disorder (MDD) from healthy controls, numerous peripheral biomarkers have been proposed. To date, no comprehensive evaluation of the existence of bias favoring the publication of significant results or inflating effect sizes has been conducted. METHODS: Here, we performed a comprehensive review of meta-analyses of peripheral nongenetic biomarkers that could discriminate individuals with MDD from nondepressed controls. PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched through April 10, 2015. RESULTS: From 15 references, we obtained 31 eligible meta-analyses evaluating biomarkers in MDD (21,201 cases and 78,363 controls). Twenty meta-analyses reported statistically significant effect size estimates. Heterogeneity was high (I2 >= 50%) in 29 meta-analyses. We plausibly assumed that the true effect size for a meta-analysis would equal the one of its largest study. A significant summary effect size estimate was observed for 20 biomarkers. We observed an excess of statistically significant studies in 21 meta analyses. The summary effect size of the meta-analysis was higher than the effect of its largest study in 25 meta-analyses, while 11 meta-analyses had evidence of small-study effects. CONCLUSIONS: Our findings suggest that there is an excess of studies with statistically significant results in the literature of peripheral biomarkers for MDD. The selective publication of 'positive studies' and the selective reporting of outcomes are possible mechanisms. Effect size estimates of meta-analyses may be inflated in this literature. PMID- 26808273 TI - Overconfidence and Career Choice. AB - People self-assess their relative ability when making career choices. Thus, confidence in their own abilities is likely an important factor for selection into various career paths. In a sample of 711 first-year students we examine whether there are systematic differences in confidence levels across fields of study. We find that our experimental confidence measures significantly vary between fields of study: While students in business related academic disciplines (Political Science, Law, Economics, and Business Administration) exhibit the highest confidence levels, students of Humanities range at the other end of the scale. This may have important implications for subsequent earnings and professions students select themselves in. PMID- 26808274 TI - Cryptic Biodiversity and the Origins of Pest Status Revealed in the Macrogenome of Simulium colombaschense (Diptera: Simuliidae), History's Most Destructive Black Fly. AB - The European black fly Simulium (Simulium) colombaschense (Scopoli), once responsible for as many as 22,000 livestock deaths per year, is chromosomally mapped, permitting its evolutionary relationships and pest drivers to be inferred. The species is 12 fixed inversions removed from the standard sequence of the subgenus Simulium. Three of these fixed inversions, 38 autosomal polymorphisms, and a complex set of 12 X and 6 Y chromosomes in 29 zygotic combinations uniquely characterize S. colombaschense and reveal 5 cytoforms: 'A' in the Danube watershed, 'B' in Italy's Adige River, 'C' in the Aliakmonas River of Greece, 'D' in the Aoos drainage in Greece, and 'E' in the Bela River of Slovakia. 'C' and 'D' are reproductively isolated from one another, and 'B' is considered a cytotype of 'A,' the probable name bearer of colombaschense. The species status of 'E' cannot be determined without additional collections. Three derived polytene sequences, based on outgroup comparisons, place S. colombaschense in a clade of species composed of the S. jenningsi, S. malyschevi, and S. reptans species groups. Only cytoforms 'A' and 'B' are pests. Within the Simuliidae, pest status is reached through one of two principal pathways, both of which promote the production of large populations of blood-seeking flies: (1) colonization of the world's largest rivers (habitat specialization) or (2) colonization of multiple habitat types (habitat generalization). Evolutionary acquisition of the ability to colonize large rivers by an ancestor of the S. jenningsi-malyschevi-reptans clade set the scene for the pest status of S. colombaschense and other big-river members of the clade. In an ironic twist, the macrogenome of S. colombaschense reveals that the name associated with history's worst simuliid pest represents a complex of species, two or more of which are nonpests potentially vulnerable to loss of their limited habitat. PMID- 26808275 TI - Comparison of the Nutritional Status of Overseas Refugee Children with Low Income Children in Washington State. AB - INTRODUCTION: The extent that the dual burden of undernutrition and overnutrition affects refugee children before resettlement in the US is not well described. OBJECTIVE: To describe the prevalence of wasting, stunting, overweight, and obesity among refugee children ages 0-10 years at their overseas medical screening examination prior to resettlement in Washington State (WA), and to compare the nutritional status of refugee children with that of low-income children in WA. METHODS: We analyzed anthropometric measurements of 1047 refugee children ages 0-10 years old to assess their nutritional status at the overseas medical screening examination prior to resettlement in WA from July 2012--June 2014. The prevalence estimates of the nutritional status categories were compared by country of origin. In addition, the nutritional status of refugee children age 0-5 years old were compared to that of low-income children in WA from the Center for Disease Control and Prevention's Pediatric Nutrition Surveillance System. RESULTS: A total of 982 children were eligible for the study, with the majority (65%) from Somalia, Iraq and Burma. Overall, nearly one-half of all refugee children had at least one form of malnutrition (44.9%). Refugee children ages 0 10 years were affected by wasting (17.3%), stunting (20.1%), overweight (7.6%) and obesity (5.9%). Among children 0-5 years old, refugee children had a significantly higher prevalence of wasting (14.3% versus 1.9%, p<0.001) and stunting (21.3% versus 5.5%, p<0.001), and a lower prevalence of obesity (6.2% versus 12.9%, p<0.001) than low-income children in WA. CONCLUSION: The dual burden of under- and over-nutrition among incoming refugee children as well as their overall difference in prevalence of nutritional status categories compared to low-income children in WA provides evidence for the importance of tailored interventions to address the nutritional needs of refugee children. PMID- 26808276 TI - Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology. AB - BACKGROUND: Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15-60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause. METHODS: We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology. RESULTS: Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001). CONCLUSIONS: Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation. PMID- 26808277 TI - "Real-Time" Monitoring of Under-Five Mortality: Lessons for Strengthened Vital Statistics Systems. PMID- 26808280 TI - Modulated photon radiotherapy (XMRT): an algorithm for the simultaneous optimization of photon beamlet energy and intensity in external beam radiotherapy (EBRT) planning. AB - This is a proof of principle study on an algorithm for optimizing external beam radiotherapy in terms of both photon beamlet energy and fluence. This simultaneous beamlet energy and fluence optimization is denoted modulated photon radiotherapy (XMRT). XMRT is compared with single-energy intensity modulated radiotherapy (IMRT) for five clinically relevant test geometries to determine whether treating beamlet energy as a decision variable improves the dose distributions. All test geometries were modelled in a cylindrical water phantom. XMRT optimized the fluence for 6 and 18 MV beamlets while IMRT optimized with only 6 MV and only 18 MV. CERR (computational environment for radiotherapy research) was used to calculate the dose deposition matrices and the resulting dose for XMRT and IMRT solutions. Solutions were compared via their dose volume histograms and dose metrics, such as the mean, maximum, and minimum doses for each structure. The homogeneity index (HI) and conformity number (CN) were calculated to assess the quality of the target dose coverage. Complexity of the resulting fluence maps was minimized using the sum of positive gradients technique. The results showed XMRT's ability to improve healthy-organ dose reduction while yielding comparable coverage of the target relative to IMRT for all geometries. All three energy-optimization approaches yielded similar HI and CNs for all geometries, as well as a similar degree of fluence map complexity. The dose reduction provided by XMRT was demonstrated by the relative decrease in the dose metrics for the majority of the organs at risk (OARs) in all geometries. Largest reductions ranged between 5% to 10% in the mean dose to OARs for two of the geometries when compared with both single-energy IMRT schemes. XMRT has shown potential dosimetric benefits through improved OAR sparing by allowing beam energy to act as a degree of freedom in the EBRT optimization process. PMID- 26808281 TI - Transparency in Biomedical Research: Clinical Trials. PMID- 26808278 TI - Genome Analysis of the Biotechnologically Relevant Acidophilic Iron Oxidising Strain JA12 Indicates Phylogenetic and Metabolic Diversity within the Novel Genus "Ferrovum". AB - BACKGROUND: Members of the genus "Ferrovum" are ubiquitously distributed in acid mine drainage (AMD) waters which are characterised by their high metal and sulfate loads. So far isolation and microbiological characterisation have only been successful for the designated type strain "Ferrovum myxofaciens" P3G. Thus, knowledge about physiological characteristics and the phylogeny of the genus "Ferrovum" is extremely scarce. OBJECTIVE: In order to access the wider genetic pool of the genus "Ferrovum" we sequenced the genome of a "Ferrovum"-containing mixed culture and successfully assembled the almost complete genome sequence of the novel "Ferrovum" strain JA12. PHYLOGENY AND LIFESTYLE: The genome-based phylogenetic analysis indicates that strain JA12 and the type strain represent two distinct "Ferrovum" species. "Ferrovum" strain JA12 is characterised by an unusually small genome in comparison to the type strain and other iron oxidising bacteria. The prediction of nutrient assimilation pathways suggests that "Ferrovum" strain JA12 maintains a chemolithoautotrophic lifestyle utilising carbon dioxide and bicarbonate, ammonium and urea, sulfate, phosphate and ferrous iron as carbon, nitrogen, sulfur, phosphorous and energy sources, respectively. UNIQUE METABOLIC FEATURES: The potential utilisation of urea by "Ferrovum" strain JA12 is moreover remarkable since it may furthermore represent a strategy among extreme acidophiles to cope with the acidic environment. Unlike other acidophilic chemolithoautotrophs "Ferrovum" strain JA12 exhibits a complete tricarboxylic acid cycle, a metabolic feature shared with the closer related neutrophilic iron oxidisers among the Betaproteobacteria including Sideroxydans lithotrophicus and Thiobacillus denitrificans. Furthermore, the absence of characteristic redox proteins involved in iron oxidation in the well-studied acidophiles Acidithiobacillus ferrooxidans (rusticyanin) and Acidithiobacillus ferrivorans (iron oxidase) indicates the existence of a modified pathway in "Ferrovum" strain JA12. Therefore, the results of the present study extend our understanding of the genus "Ferrovum" and provide a comprehensive framework for future comparative genome and metagenome studies. PMID- 26808279 TI - Personality Traits Predict the Developmental Course of Externalizing: A Four-Wave Longitudinal Study Spanning Age 17 to Age 29. AB - The objective of the present study was to determine whether and how personality predicts the developmental course of externalizing problems, including antisocial behavior and substance dependence. In a large, population-based longitudinal study (N = 1,252), the 11 personality traits assessed by the Multidimensional Personality Questionnaire were measured at age 17, and DSM diagnoses of adult antisocial behavior, alcohol dependence, and drug dependence were obtained at ages 17, 20, 24, and 29. We fit a quadratic multiple indicator latent growth model where the three diagnoses loaded onto an externalizing factor. This model fit the data well, and externalizing increased until it started to decline at age 24. High aggression and low control were the most significant predictors of the development of externalizing, with aggression playing a significant role in the development of externalizing across the 12-year time span, and control predicting the development from age 17 to 24. The findings highlight the importance of considering the developmental course of externalizing in the context of personality and suggest that the specific personality traits of aggression and control might be targeted in externalizing prevention and intervention programs. PMID- 26808282 TI - Reading Fluency in School-Aged Children with Bilateral Astigmatism. AB - PURPOSE: To compare oral reading fluency (ORF) in students with no/low astigmatism and moderate/high astigmatism and to assess the impact of spectacle correction on ORF in moderate and high astigmats. METHODS: Subjects were third- to eighth-grade students from a highly astigmatic population. Refractive error was determined through subjectively refined cycloplegic autorefraction. Data from students with ocular abnormalities, anisometropia, symptomatic binocular vision disorders, or refractive error that did not meet study criteria (no/low [cylinder < 1.00 both eyes, no significant myopia/hyperopia], moderate [cylinder >= 1.00 D both eyes, mean >= 1.00 D and < 3.00 D], or high astigmatism group [cylinder >= 1.00 D both eyes, mean >= 3.00 D]) were excluded. Oral reading fluency was tested with a modified version of the Dynamic Indicators of Basic Early Literacy Skills (DIBELS) Next test of ORF. No/low astigmats were tested without spectacles; astigmats were tested with and without spectacles. Mean ORF was compared in no/low astigmats and astigmats (with and without correction). Improvement in ORF with spectacles was compared between moderate and high astigmats. RESULTS: The sample included 130 no/low, 67 moderate, and 76 high astigmats. ORF was lower in uncorrected astigmats than in no/low astigmats (p = 0.011). ORF did not significantly differ in no/low astigmats and corrected astigmats (p = 0.10). ORF significantly improved with spectacle correction in high astigmats (p = 0.001; mean improvement, 6.55 words per minute) but not in moderate astigmats (p = 0.193; mean improvement, 1.87 words per minute). Effects of spectacle wear were observed in students who read smaller text stimuli (older grades). CONCLUSIONS: ORF is significantly reduced in students with bilateral astigmatism (>=1.00D) when uncorrected but not when best-corrected compared with their nonastigmatic peers. Improvement in ORF with spectacle correction is seen in high astigmats but not in moderate astigmats. These data support the recommendation for full-time spectacle wear in astigmatic students, particularly those with high astigmatism. PMID- 26808285 TI - Direct Revascularization with Autotransplant Technique for a True Aneurysm of the Renal Artery 20 Years after Kidney Transplantation. AB - BACKGROUND: True degenerative aneurysm of renal artery represents a very rare evolution in kidney transplantation. The cases presented in the literature are usually perianastomotic or mycotic pseudoaneurysm related to surgical technical defects or local infections. CASE REPORT: Herewith, we present the case of a voluminous true aneurysm developed in a young patient transplanted at our hospital 20 years before. All follow-up ultrasounds were always normal until the last disclosing a voluminous aneurysm of the transplanted renal artery. The subsequent angio-CT-scan confirmed the presence of a 52-mm saccular dilatation of the renal artery. For the complex anatomy, the endovascular approach was excluded, and a surgical revascularization was staged. We treated this lesion with the autotransplant technique, preserving the transplanted kidney, resecting the aneurysm, and performing a direct anastomosis after cold perfusion of the kidney. CONCLUSIONS: The autotransplant technique demonstrated to be a safe and effective approach in this challenging and very unusual situation. PMID- 26808286 TI - Preliminary Experience with the GORE((r)) EXCLUDER((r)) Iliac Branch Endoprosthesis for Common Iliac Aneurysm Endovascular Treatment. AB - BACKGROUND: The aim of this study is to assess the safety and the short-term results of endovascular treatment of common iliac artery (CIA) aneurysms using the new GORE EXCLUDER iliac branch endoprosthesis (IBE) device. METHODS: The study is a retrospective with prospective follow-up nonrandomized, single-arm evaluation. Patients with a CIA aneurysm (diameter >30 mm) extending to the iliac bifurcation underwent endovascular treatment with the Gore IBE. Anatomic and procedural data were collected. Computed tomography angiography (CTA) was performed within the 30 days after the procedure and every 6 month. Thirty-day and at least 6-months outcomes were investigated. RESULTS: From February 2014 to December 2014, 10 male patients with aneurysmal CIA (mean age 75 years old) underwent consecutive endovascular treatment with the Gore IBE. The CIA aneurysm (mean diameter 43.2 mm, range 32-49) treated with the Gore IBE was associated with an abdominal aortic aneurysm (AAA) in 5 patients. One patient had a previous AAA open repair. CIA aneurysm was bilateral in 5 patients. Preliminary procedure of internal iliac artery embolization was performed in 3 patients. Technical success rate of the Gore IBE implantation was 100% with a median fluoroscopy time of 35 min (range 12-64, +/-16) and median contrast load of 150 mL (range 100-250, +/-45). No perioperative complications were observed. Median length of stay was 4 days (range 3-7, +/-2). One aortic type Ia endoleak was observed on the postoperative CT scan requiring an aortic extension at day 3. Branch patency was observed in all 10 patients at 1 month and 9 patients at 6 month. All CIA aneurysms were excluded without type Ib or type III endoleak. CONCLUSIONS: The technical success and short-term results demonstrate encouraging results and clinical benefits of the new GORE EXCLUDER IBE. A longer follow-up is needed to assess midterm and long-term results. PMID- 26808287 TI - Validation of a French-Language Version of the Spatial Hearing Questionnaire, Cluster Analysis and Comparison with the Speech, Spatial, and Qualities of Hearing Scale. AB - OBJECTIVES: To validate a French-language version of the spatial hearing questionnaire (SHQ), including investigating its internal structure using cluster analysis and exploring its construct validity on a large population of hearing impaired (HI) and normal-hearing (NH) subjects, and to compare the SHQ with the speech, spatial, and qualities of hearing scale (SSQ) in the same population. DESIGN: The SHQ was translated in accordance with the principles of the Universalist Model of cross-cultural adaptation of patient-reported outcome instruments. The SSQ and SHQ were then presented in a counterbalanced order, in a self-report mode, in a population of 230 HI subjects (mean age = 54 years and pure-tone audiometry [PTA] on the better ear = 28 dB HL) and 100 NH subjects (mean age = 21 years). The SHQ feasibility, readability, and psychometric properties were systematically investigated using reliability indices, cluster, and factor analyses and multiregression analyses. SHQ characteristics were compared both to different literature data obtained with different language versions and to the SSQ scores obtained in the same population. RESULTS: Internal validity was high and very good reproducibility of scores and intersubject variability were obtained across the 24 items between the English and French SHQ for NH subjects. Factor and cluster analyses concurred in identifying five correlated factors, corresponding to several SHQ subscales: (1) speech in noise (corresponding to SHQ subscales 7 and 8), (2) localization of voice sounds from behind, (3) speech in quiet (corresponding to SHQ subscale 1), (4) localization of everyday sounds, and (5) localization of voices and music (corresponding to parts of the SHQ localization subscale). Correlations between SSQ subscales and SHQ factors identified the greatest correlations between SHQ factors 2, 4, and 5 and SSQ spatial subscales, whereas SHQ factor 1 had the greatest correlation with SSQ_speech. SHQ and SSQ scores were similar, whether in NH subjects (8.5 versus 8.4) or in HI subjects (6.6 for both), sharing more than 80% of variance. The SHQ localization subscale gave similar scores as the SSQ spatial subscale, sharing more than 75% of variance. Construct validity identified better ear PTA and PTA asymmetry as the two main predictors of SHQ scores, to a degree similar to that seen for the SSQ. The SHQ was shorter, easier to read and less sensitive to the number of years of formal education than the SSQ, but this came at a cost of ecological validity, which was rated higher for the SSQ than for the SHQ. CONCLUSIONS: A comparison of factor analysis outcomes among the English, Dutch, and French versions of the SHQ confirmed good conceptual equivalence across languages and robustness of the SHQ for use in international settings. In addition, SHQ and SSQ scores showed remarkable similarities, suggesting the possibility of extrapolating the results from one questionnaire to the other. Although the SHQ was originally designed in a population of cochlear implant patients, the present results show that its usefulness could easily be extended to noncochlear-implanted, HI subjects. PMID- 26808288 TI - Detection of Airborne Methicillin-Resistant Staphylococcus aureus Inside and Downwind of a Swine Building, and in Animal Feed: Potential Occupational, Animal Health, and Environmental Implications. AB - Aerosolized methicillin-resistant Staphylococcus aureus (MRSA) was sampled inside and downwind of a swine facility. Animal feed was sampled before and after entry into the swine facility. Aerosolized particles were detected using an optical particle counter for real-time measurement and with an Andersen sampler to detect viable MRSA. Molecular typing and antimicrobial susceptibility testing were performed on samples collected. Viable MRSA organisms isolated inside the swine facility were primarily associated with particles >5 um, and those isolated downwind from the swine facility were associated with particles <5 um. MRSA isolates included spa types t008, t034, and t5706 and were resistant to methicillin, tetracycline, clindamycin, and erythromycin. Animal feed both before and after entry into the swine facility tested positive for viable MRSA. These isolates were of similar spa types as the airborne MRSA organisms. Air samples collected after power washing with a biocide inside the swine facility resulted in no viable MRSA organisms detected. This pilot study showed that the ecology of MRSA is complex. Additional studies are warranted on the maximum distance that viable MRSA can be emitted outside the facility, and the possibility that animal feed may be a source of contamination. PMID- 26808289 TI - Design, Synthesis, and Biological Evaluation of Scutellarein Derivatives Based on Scutellarin Metabolic Mechanism In Vivo. AB - Three series of scutellarein derivatives have been designed and synthesized based on metabolic mechanism of scutellarin (1) in vivo. Their thrombin inhibition activities were tested through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1,1 diphenyl-2-picrylhydrazyl radical (DPPH) assay and the ability to protect PC12 cells against H2 O2 -induced cytotoxicity, and their solubilities were evaluated by ultraviolet (UV) spectrophotometer. The results showed that the two isopropyl groups substituted derivative (18c) demonstrated stronger anticoagulant activity, better water solubility, and good antioxidant activity compared with scutellarein (2), which warrants further development of 18c as a promising agent for ischemic cerebrovascular disease treatment. PMID- 26808291 TI - Complete closure of a large gastric perforation caused by percutaneous endoscopic gastrostomy using over-the-scope clips. PMID- 26808292 TI - Impacts of addition of natural zeolite or a nitrification inhibitor on antibiotic resistance genes during sludge composting. AB - Composting is commonly used for the treatment and resource utilization of sewage sludge, and natural zeolite and nitrification inhibitors can be used for nitrogen conservation during sludge composting, while their impacts on ARGs control are still unclear. Therefore, three lab-scale composting reactors, A (the control), B (natural zeolite addition) and C (nitrification inhibitor addition of 3,4 dimethylpyrazole phosphate, DMPP), were established. The impacts of natural zeolite and DMPP on the levels of ARGs were investigated, as were the roles that heavy metals, mobile genetic elements (MGEs) and the bacterial community play in ARGs evolution. The results showed that total ARGs copies were enriched 2.04 and 1.95 times in reactors A and C, respectively, but were reduced by 1.5% in reactor B due to the reduction of conjugation and co-selection of heavy metals caused by natural zeolite. Although some ARGs (blaCTX-M, blaTEM, ermB, ereA and tetW) were reduced by 0.3-2 logs, others (ermF, sulI, sulII, tetG, tetX, mefA and aac(6')-Ib cr) increased by 0.3-1.3 logs after sludge composting. Although the contributors for the ARGs profiles in different stages were quite different, the results of a partial redundancy analysis, Mantel test and Procrustes analysis showed that the bacterial community was the main contributor to the changes in ARGs compared to MGEs and heavy metals. Network analysis determined the potential host bacteria for various ARGs and further confirmed our results. PMID- 26808290 TI - Reticulate evolutionary history and extensive introgression in mosquito species revealed by phylogenetic network analysis. AB - The role of hybridization and subsequent introgression has been demonstrated in an increasing number of species. Recently, Fontaine et al. (Science, 347, 2015, 1258524) conducted a phylogenomic analysis of six members of the Anopheles gambiae species complex. Their analysis revealed a reticulate evolutionary history and pointed to extensive introgression on all four autosomal arms. The study further highlighted the complex evolutionary signals that the co-occurrence of incomplete lineage sorting (ILS) and introgression can give rise to in phylogenomic analyses. While tree-based methodologies were used in the study, phylogenetic networks provide a more natural model to capture reticulate evolutionary histories. In this work, we reanalyse the Anopheles data using a recently devised framework that combines the multispecies coalescent with phylogenetic networks. This framework allows us to capture ILS and introgression simultaneously, and forms the basis for statistical methods for inferring reticulate evolutionary histories. The new analysis reveals a phylogenetic network with multiple hybridization events, some of which differ from those reported in the original study. To elucidate the extent and patterns of introgression across the genome, we devise a new method that quantifies the use of reticulation branches in the phylogenetic network by each genomic region. Applying the method to the mosquito data set reveals the evolutionary history of all the chromosomes. This study highlights the utility of 'network thinking' and the new insights it can uncover, in particular in phylogenomic analyses of large data sets with extensive gene tree incongruence. PMID- 26808293 TI - Acquisition of Lateralized Predation Behavior Associated with Development of Mouth Asymmetry in a Lake Tanganyika Scale-Eating Cichlid Fish. AB - The scale-eating cichlid Perissodus microlepis with asymmetric mouth is an attractive model of behavioral laterality: each adult tears off scales from prey fishes' left or right flanks according to the direction in which its mouth is skewed. To investigate the development of behavioral laterality and mouth asymmetry, we analyzed stomach contents and lower jaw-bone asymmetry of various sized P. microlepis (22 <= SL<115 mm) sampled in Lake Tanganyika. The shapes of the pored scales found in each specimen's stomach indicated its attack side preference. Early-juvenile specimens (SL<45 mm) feeding mainly on zooplankton exhibited slight but significant mouth asymmetry. As the fish acquired scale eating (45 mm <= SL), attack side preference was gradually strengthened, as was mouth asymmetry. Among size-matched individuals, those with more skewed mouths ate more scales. These findings show that behavioral laterality in scale-eating P. microlepis is established in association with development of mouth asymmetry which precedes the behavioral acquisition, and that this synergistic interaction between physical and behavioral literalities may contribute to efficient scale eating. PMID- 26808294 TI - Isolation of functionally active and highly purified neuronal mitochondria from human cortex. AB - BACKGROUND: Functional and structural properties of mitochondria are highly tissue and cell dependent, but isolation of highly purified human neuronal mitochondria is not currently available. NEW METHOD: We developed and validated a procedure to isolate purified neuronal mitochondria from brain tissue. The method combines Percoll gradient centrifugation to obtain synaptosomal fraction with nitrogen cavitation mediated synaptosome disruption and extraction of mitochondria using anti mitochondrial outer membrane protein antibodies conjugated to magnetic beads. The final products of isolation are non synaptosomal mitochondria, which are a mixture of mitochondria isolated from different brain cells (i.e. neurons, astrocytes, oligodendrocytes, microglia) and synaptic mitochondria, which are of neuronal origin. This method is well suited for preparing functional mitochondria from human cortex tissue that is surgically extracted. RESULTS: The procedure produces mitochondria with minimal cytoplasmic contaminations that are functionally active based on measurements of mitochondrial respiration as well as mitochondrial protein import. The procedure requires approximately four hours for the isolation of human neuronal mitochondria and can also be used to isolate mitochondria from mouse/rat/monkey brains. COMPARISON WITH EXISTING METHODS AND CONCLUSIONS: This method will allow researchers to study highly enriched neuronal mitochondria without the confounding effect of cellular and organelle contaminants. PMID- 26808295 TI - Perceptions of Cancer Risk, Cause, and Needs in Participants from Low Socioeconomic Background at Risk for Hereditary Cancer. AB - The purpose of this study was to describe perceptions of cancer risk, cause, and needs in participants from a low socioeconomic background at risk for hereditary cancer. We surveyed 307 individuals with the Cancer Awareness and Needs survey and received 128 responses (41.6% response rate). Family history, genetics, and tobacco use were selected most frequently as a cause of cancer; 36% (n = 46) selected fate and/or God's will. A total of 87.5% (n = 112) understood that having a close family member with breast cancer could increase personal risk; however responses were varied when asked if this was related to risk for other cancers. Most participants had undergone cancer screening, half reported undergoing breast magnetic resonance imaging, which was associated with personal (p < 0.01) and family cancer history (p = 0.03). An additional 76.6% (n = 98) felt informed about cancer screening and most received information from health care providers and family or friends. Ensuring that patients and clinicians are educated about hereditary cancer risk, detection, and prevention should be priorities for future research. PMID- 26808296 TI - Helicobacter pylori induces Snail expression through ROS-mediated activation of Erk and inactivation of GSK-3beta in human gastric cancer cells. AB - Helicobacter pylori (H. pylori) infection has been known to be implicated in human gastric carcinogenesis. Snail, the zinc-finger transcription factor known as a key inducer of changes in the cell shape and morphogenetic movement, is aberrantly overexpressed and correlates with lymph node metastasis in gastric cancer. In the present study, we investigated whether H. pylori could induce Snail activation to provoke these changes. Using a cell scatter assay, we noticed that human gastric cancer AGS cells infected with H. pylori underwent morphological changes as well as disruption of cell-cell interaction, which was then reversed by silencing of Snail by use of small interfering RNA (siRNA). In addition, infection with H. pylori resulted in an increased intracellular level of Snail in gastric cancer cells, which was abrogated in the presence of U0126 and LY294002, inhibitors of MEK/Erk and PI3K/Akt pathways, respectively. Cycloheximide pulse-chase experiments coupled with immunocytochemical analysis revealed that the induction of Snail by H. pylori was regulated at multiple levels, including increased transcription of Snail mRNA, inhibition of protein degradation, and enhancement of nuclear translocation of Snail. Pre-treatment of AGS cells with N-acetylcysteine, a well-known reactive oxygen species (ROS) scavenger, attenuated the H. pylori-induced activation of Erk, its binding to Snail promoter, inactivation of GSK-3beta, and accumulation of Snail. Collectively, these findings suggest that the upregulation of Snail expression induced by H. pylori and transformation to a spindle-like shape as a consequence in gastric cancer cells are attributable to ROS-mediated activation of Erk and the inhibition of GSK-3beta signaling. (c) 2016 Wiley Periodicals, Inc. PMID- 26808297 TI - Positron emission tomography response criteria in solid tumours criteria for quantitative analysis of [18F]-fluorodeoxyglucose positron emission tomography with integrated computed tomography for treatment response assessment in metastasised solid tumours: All that glitters is not gold. AB - For solid tumours, quantitative analysis of [(18)F]-fluorodeoxyglucose positron emission tomography with integrated computed tomography potentially can have significant value in early response assessment and thereby discrimination between responders and non-responders at an early stage of treatment. Standardised strategies for this analysis have been proposed, and the positron emission tomography response criteria in solid tumours (PERCIST) criteria can be regarded as the current standard to perform quantitative analysis in a research setting, yet is not implemented in daily practice. However, several exceptions and limitations limit the feasibility of PERCIST criteria. In this article, we point out dilemmas that arise when applying proposed criteria like PERCIST on an expansive set of patients with metastasised solid tumours. Clinicians and scientists should be aware of these limitations to prevent that methodological issues impede successful introduction of research data into clinical practice. Therefore, to deliver on the high potential of quantitative imaging, consensus should be reached on a standardised, feasible and clinically useful analysis methodology. This methodology should be applicable in the majority of patients, tumour types and treatments. PMID- 26808299 TI - Characteristics of Patients with Smear-Negative Pulmonary Tuberculosis (TB) in a Region with High TB and HIV Prevalence. AB - INTRODUCTION: Smear-negative pulmonary TB (SNPT) represents 30-60% of all pulmonary TB cases. The mortality of these patients can reach 25% in populations with high prevalence of HIV infection, and 10-20% of TB transmission at the population level are attributable to SNPT cases. METHODS: We conducted a retrospective study to evaluate epidemiological, clinical, and radiological characteristics of patients with SNPT and to compare these with patients who were diagnosed as having smear-positive pulmonary TB (SPPT). All adult patients (>= 18 years old) with a positive culture for Mycobacterium tuberculosis, and a diagnosis of pulmonary TB were included in the study. RESULTS: 198 patients met the inclusion criteria (positive culture for Mycobacterium tuberculosis) and were included in the analysis. Of these patients, 69 (34.8%) were smear positive (SPPT) and 129 (65.2%) were smear negative (SNPT). In univariate analysis, cough, dyspnea, and hemoptysis were less frequent in SNPT patients in comparison with SPPT patients. In a multivariate model, having no cough and no radiographic pattern typical of TB were the characteristics independently associated with a diagnosis of SNPT. CONCLUSIONS: We found a very high prevalence of SNPT among patients with TB in a setting with high TB and HIV prevalence. The absence of cough in the presence of other symptoms suggestive of TB, and having no radiographic pattern typical of TB where independent predictors of SNPT. PMID- 26808300 TI - Copper mediated carbometalation reactions. AB - Since the first discovery of carbocupration of alkynes in the 1970s a tremendous amount of research has been carried out in this field. The exceptionally high selectivities obtained attribute to the great synthetic value of carbocupration reactions. This tutorial review will present the most important features of carbocupration of alkynes and highlight the most relevant reviews. Then a comprehensive review of copper mediated carbometalation of cyclopropenes will follow. The latter method has received much attention over the last decade as it allows the highly selective construction of poly-substituted cyclopropanes which can be transformed into acyclic derivatives bearing one or multiple tertiary or quaternary carbon stereocenters. PMID- 26808298 TI - Role of neoadjuvant treatment in clinical T2N0M0 oesophageal cancer: results from a retrospective multi-center European study. AB - AIMS: The aims of this study were to compare short- and long-term outcomes for clinical T2N0 oesophageal cancer with analysis of (i) primary surgery (S) versus neoadjuvant therapy plus surgery (NS), (ii) squamous cell carcinoma and adenocarcinoma subsets; and (iii) neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy. METHODS: Data were collected from 30 European centres from 2000 to 2010. Among 2944 included patients, 355 patients (12.1%) had cT2N0 disease; 285 (S) and 70 (NS), were compared in terms of short- and long-term outcomes. Propensity score matching analyses were used to compensate for differences in baseline characteristics. RESULTS: No significant differences between the groups were shown in terms of in hospital morbidity and mortality. Nodal disease was observed in 50% of S-group at the time of surgery, with 20% pN2/N3. Utilisation of neoadjuvant therapy was associated with significant tumour downstaging as reflected by increases in pT0, pN0 and pTNM stage 0 disease, this effect was further enhanced with neoadjuvant chemoradiotherapy. After adjustment on propensity score and confounding factors, for all patients and subset analysis of squamous cell and adenocarcinoma, neoadjuvant therapy had no significant effect upon survival or recurrence (overall, loco-regional, distant or mixed) compared to surgery alone. There were no significant differences between neoadjuvant chemotherapy and chemoradiotherapy in short- or long-term outcomes. CONCLUSION: The results of this study suggest that a surgery alone treatment approach should be recommended as the primary treatment approach for cT2N0 oesophageal cancer despite 50% of patients having nodal disease at the time of surgery. PMID- 26808301 TI - Urinary Continence in German and Brazilian Individuals With Spina Bifida: Influence of Intermittent Catheterization. AB - PURPOSE: The purpose of this study was to identify the factors associated with acquisition of urinary continence following introduction of intermittent catheterization (IC). STUDY DESIGN: Cross-sectional study. SUBJECTS AND SETTING: The study sample comprised 104 females and 84 males. Their median age was 11 years (interquartile range = 6.0-22.0 years). Data were collected in 2 settings, the Rehabilitation Hospital in Belo Horizonte Brazil and Dortmund University North-Rhine, Westphalia, Germany. METHODS: Ninety-four Brazilian and 94 German individuals who had experienced IC participated in the study. Data were collected using printed (Brazil) and online (Germany) questionnaires and analyzed using multivariate logistical regression and analysis of variance. RESULTS: Out of the 188 participants, 62.2% (117) achieved complete or partial continence. We found that increasing the frequency of IC increases the likelihood that the patient will acquire continence with IC. Using self-catheterization can increase the likelihood of acquiring continence (partial or complete) up to 2.9 times, in relation to someone who uses no self-catheterization. CONCLUSIONS: Among patients with spina bifida and neurogenic bladder dysfunction, acquisition of urinary continence after initiating IC was influenced by the use of self-catheterization and daily frequency of IC. PMID- 26808302 TI - Reduction of Catheter-Associated Urinary Tract Infections Through the Use of an Evidence-Based Nursing Algorithm and the Implementation of Shift Nursing Rounds: A Quality Improvement Project. AB - Catheter-associated urinary tract infections (CAUTIs) are the most common hospital-acquired infections. The purpose of this quality improvement (QI) project was to successfully implement a nurse-led evidence-based practice change designed to reduce CAUTIs in a cardiac intensive care and step-down unit. The QI project was implemented using a convenience sample of patients admitted to the cardiac intensive care and step-down unit.Evaluation data were collected 3 months preimplementation and 9 months postimplementation. We used Wick's Check-Plan-Do Check-Act model of continuous QI to guide the project. A statistically significant change in the number of CAUTIs (P = .009) and CAUTI occurrences (P = .005) was observed following the intervention. The number of indwelling catheter days and indwelling catheter utilization did not significantly differ following implementation of the intervention. Nurse compliance with the intervention was computed for each month; the average compliance rate was 91%. Findings from this project indicate that a nurse-led evidence-based practice project exerted a positive influence on CAUTI occurrences. PMID- 26808303 TI - Health-Related Quality of Life in Persons With Ostomies Managed in an Outpatient Care Setting. AB - PURPOSE: We examined health-related quality of life (HRQOL) in persons with ostomies receiving outpatient care. We also analyzed relationships among HRQOL, demographic, and pertinent clinical factors. DESIGN: We used a descriptive, exploratory, cross-sectional study design to collect and analyze data. Data in this article are a secondary analysis of data collected from a primary study, developed by Santos and Gomboski, on the adaptation and validation of the City of Hope-Quality of Life-Ostomy Questionnaire (COH-QOL-OQ) to the Portuguese language in Brazil. SUBJECTS AND SETTING: A convenience sample of 215 adults living with an ostomy was evaluated. Slightly more than half (51.6%) were men, 67.5% underwent colostomy surgery, and 59.1% underwent cancer-related ostomy surgery. Subjects received care in specialized health care units in 3 cities in the Brazilian state of Rio Grande do Sul. METHODS: After approval by the Research Ethics Committee and permission from health care units, data were collected using 2 instruments: the World Health Organization Quality of Life-Short Version (WHOQOL-Bref) (generic HRQOL instrument) and the COH-QOL-OQ (disease specific HRQOL instrument). Data were analyzed using chi test and logistic regression (via a stepwise forward method). Patients were classified into 3 groups according to the means and standard deviations of the scores: low, moderate, and high quality of life (QOL). RESULTS: Ostomy patients had total scores of 69.6 +/- 20.2 and 6.1 +/- 1.4 for the WHOQOL-Bref and COH-QOL-OQ instruments, respectively. Patients with shorter times since their ostomy creation had worse scores on both the specific QOL (P = .006) and generic QOL (P = .019) instruments. Patients who did not practice religion (P = .027; odds ratio [OR] = 3.39) and those without a partner/spouse (P = .007; OR = 4.90) had increased probability of having worse scores on the WHOQOL-Bref (generic instrument). CONCLUSION: Persons living with ostomies were found to have scores indicating moderate HRQOL on a disease specific and generic instrument. Shorter time since ostomy creation, lack of religious practice, and lack of a partner negatively influenced the HRQOL of these patients. PMID- 26808304 TI - The VCU Pressure Ulcer Summit-Developing Centers of Pressure Ulcer Prevention Excellence: A Framework for Sustainability. AB - Hospital-acquired pressure ulcer occurrences have declined over the past decade as reimbursement policies have changed, evidence-based practice guidelines have been implemented, and quality improvement initiatives have been launched. However, the 2006-2008 Institute for Healthcare Improvement goal of zero pressure ulcers remains difficult to achieve and even more challenging to sustain. Magnet hospitals tend to have lower hospital-acquired pressure ulcer rates than non Magnet hospitals, yet many non-Magnet hospitals also have robust pressure ulcer prevention programs. Successful programs share commonalities in structure, processes, and outcomes. A national summit of 55 pressure ulcer experts was convened at the Virginia Commonwealth University Medical Center in March 2014. The group was divided into 3 focus groups; each was assigned a task to develop a framework describing components of a proposed Magnet-designated Center of Pressure Ulcer Prevention Excellence. Systematic literature reviews, analysis of exemplars, and nominal group process techniques were used to create the framework. This article presents a framework describing the proposed Magnet designated Centers of Pressure Ulcer Prevention Excellence. Critical attributes of Centers of Excellence are identified and organized according to the 4 domains of the ANCC model for the Magnet Recognition Program: transformational leadership; structural empowerment; exemplary professional practice; and new knowledge innovation and improvements. The structures, processes, and outcome measures necessary to become a proposed Center of Pressure Ulcer Prevention Excellence are discussed. PMID- 26808305 TI - Long acting analogue of the calcitonin gene-related peptide induces positive metabolic effects and secretion of the glucagon-like peptide-1. AB - The pharmacological potential of Calcitonin gene-related peptide (CGRP) beyond vasodilation is not completely understood and studies are limited by the potent vasodilatory effect and the short half-life of CGRP. In particular, the effects of CGRP on metabolic diseases are not clarified. A peptide analogue of the alpha form of CGRP (alphaAnalogue) with prolonged half-life (10.2 +/- 0.9h) in rodents was synthesised and used to determine specific metabolic effects in 3 rodent models; normal rats, diet-induced obese rats and the Leptin deficient mouse model (ob/ob mice). The alphaAnalogue (100 nmol/kg) induced elevated energy expenditure and reduced food intake after single dosing in normal rats. In addition, the alphaAnalogue increased levels of circulating Glucagon-Like Peptide-1 (GLP-1) by >60% and a specific concentration dependent CGRP-induced GLP-1 secretion was verified in a murine L-cell line. Two weeks treatment of the type 2 diabetic ob/ob mice with the alphaAnalogue caused reduction in fasting insulin levels (199 +/- 36 pM vs 332 +/- 68 pM) and a tendency to reduce fasting blood glucose (11.2 +/- 1.1mM vs 9.5 +/- 0.5mM) and % glycosylated haemoglobin (HbA1c) (5.88 +/- 0.17 vs 5.12 +/- 0.24), demonstrating a potential anti-diabetic effect. Furthermore, two weeks treatment of diet-induced obese rats with the alphaAnalogue caused reduction in food intake and a significant decline in body weight (3.6 +/- 1.9 gvs. -36 +/- 1.1g). We have demonstrated that long-acting CGRP analogues may have a therapeutic potential for the treatment of type 2 diabetes through positive metabolic effects and effect on GLP-1 secretion. PMID- 26808306 TI - Molecular Assortment of Lens Species with Different Adaptations to Drought Conditions Using SSR Markers. AB - The success of drought tolerance breeding programs can be enhanced through molecular assortment of germplasm. This study was designed to characterize molecular diversity within and between Lens species with different adaptations to drought stress conditions using SSR markers. Drought stress was applied at seedling stage to study the effects on morpho-physiological traits under controlled condition, where tolerant cultivars and wilds showed 12.8-27.6% and 9.5-23.2% reduction in seed yield per plant respectively. When juxtaposed to field conditions, the tolerant cultivars (PDL-1 and PDL-2) and wild (ILWL-314 and ILWL-436) accessions showed 10.5-26.5% and 7.5%-15.6% reduction in seed yield per plant, respectively under rain-fed conditions. The reductions in seed yield in the two tolerant cultivars and wilds under severe drought condition were 48-49% and 30.5-45.3% respectively. A set of 258 alleles were identified among 278 genotypes using 35 SSR markers. Genetic diversity and polymorphism information contents varied between 0.321-0.854 and 0.299-0.836, with mean value of 0.682 and 0.643, respectively. All the genotypes were clustered into 11 groups based on SSR markers. Tolerant genotypes were grouped in cluster 6 while sensitive ones were mainly grouped into cluster 7. Wild accessions were separated from cultivars on the basis of both population structure and cluster analysis. Cluster analysis has further grouped the wild accessions on the basis of species and sub-species into 5 clusters. Physiological and morphological characters under drought stress were significantly (P = 0.05) different among microsatellite clusters. These findings suggest that drought adaptation is variable among wild and cultivated genotypes. Also, genotypes from contrasting clusters can be selected for hybridization which could help in evolution of better segregants for improving drought tolerance in lentil. PMID- 26808308 TI - Purification of Messenger Ribonucleoprotein Particles via a Tagged Nascent Polypeptide. AB - The cytoplasmic fates of mRNAs are influenced by interactions between RNA-binding proteins and cis regulatory motifs. In the cytoplasm, mRNAs are present as messenger ribonucleoprotein particles, which include not only proteins that bind directly to the mRNA, but also additional proteins that are recruited via protein protein interactions. Many labs have sought to purify such particles from cells, with limited success. We here describe a simple two-step procedure to purify actively translated mRNAs, with their associated proteins, from polysomes. We use a reporter mRNA that encodes a protein with three streptavidin binding peptides at the N-terminus. The polysomal reporter mRNA, with associated proteins, is purified via binding to a streptavidin matrix. The method takes four days, and can be applied in any cell that can be genetically manipulated. Using Trypanosoma brucei as a model system, we routinely purified 8% of the input reporter mRNA, with roughly 22-fold enrichment relative to un-tagged mRNAs, a final reporter mRNA:total-mRNA ratio of about 1:10, and a protein purification factor of slightly over 1000-fold. Although the overall reporter mRNP composition is masked by the presence of proteins that are associated with many polysomal mRNAs, our method can be used to detect association of an RNA-binding protein that binds to specifically to a reporter mRNA. PMID- 26808307 TI - A Systematic Review on the Use of Psychosocial Interventions in Conjunction With Medications for the Treatment of Opioid Addiction. AB - Opioid use and overdose rates have risen to epidemic levels in the United States during the past decade. Fortunately, there are effective medications (ie, methadone, buprenorphine, and oral and injectable naltrexone) available for the treatment of opioid addiction. Each of these medications is approved for use in conjunction with psychosocial treatment; however, there is a dearth of empirical research on the optimal psychosocial interventions to use with these medications. In this systematic review, we outline and discuss the findings of 3 prominent prior reviews and 27 recent publications of empirical studies on this topic. The most widely studied psychosocial interventions examined in conjunction with medications for opioid addiction were contingency management and cognitive behavioral therapy, with the majority focusing on methadone treatment. The results generally support the efficacy of providing psychosocial interventions in combination with medications to treat opioid addictions, although the incremental utility varied across studies, outcomes, medications, and interventions. The review highlights significant gaps in the literature and provides areas for future research. Given the enormity of the current opioid problem in the United States, it is critical to gain a better understanding of the most effective ways to deliver psychosocial treatments in conjunction with these medications to improve the health and well-being of individuals suffering from opioid addiction. PMID- 26808309 TI - Agreements and Discrepancies between FDA Reports and Journal Papers on Biologic Agents Approved for Rheumatoid Arthritis: A Meta-Research Project. AB - BACKGROUND: Sponsors that seek to commercialize new drugs apply to the Food and Drug Administration (FDA) which independently analyzes the raw data and reports the results on its website. OBJECTIVES: This study sought to determine if there are differences between the FDA assessments and journal reports on biologic agents developed for the treatment of rheumatoid arthritis. METHODS: Available data on FDA-approved drugs were extracted from the website, and a systematic literature search was conducted to identify matching studies in peer-reviewed medical journals. Outcome measures were the American College of Rheumatology response criteria ACR20 (efficacy) and withdrawal due to adverse events (safety). As effect size odds ratios were estimated for each active trial arm vs. control arm (i.e. for both sources: FDA and journal report), followed by calculation of the ratios of the FDA and journal report odds ratios. A ratio of odds ratios not equal to 1 was categorized as a discrepancy. RESULTS: FDA reports were available for 8 of 9 FDA-approved biologic agents for rheumatoid arthritis; all identified trials (34) except one were published in peer-reviewed journals. Overall, discrepancies were noted for 20 of the 33 evaluated trials. Differences in the apparent benefit reporting were found in 39% (24/61) pairwise comparisons and in 11 cases these were statistically significant; the FDA report showed greater benefit than the journal publication in 15 comparisons and lesser benefit in 9. Differences in the reported harms were found in 51% (28/55) pairwise comparisons and were statistically significant in 5. The "signal" in FDA reports showed a less harmful effect than the journal publication in 17 comparisons whereas a more harmful effect in 11. The differences were attributed to differences in analytic approach, patient inclusion, rounding effect, and counting discrepancies. However, no differences were categorized as critical. CONCLUSION: There was no empirical evidence to suggest biased estimates between the two sources. Increased and detailed transparency in publications would improve the understanding and credibility of published results. Further, the FDA report was found to be a useful source when data are missing in the published report (i.e. reporting bias). PMID- 26808310 TI - Autopolyreactivity Confers a Holistic Role in the Immune System. AB - In this review, we summarize and discuss some key findings from the study of naturally occurring autoantibodies. The B-cell compartment of the immune system appears to recognize almost all endogenous and environmental antigens. This ability is accomplished principally through autopolyreactive humoral and cellular immune receptors. This extended autopolyreactivity (1) along immunoglobulin gene recombination contributes to the immune system's ability to recognize a very large number of self and non-self constituents; and (2) generates a vast immune network that creates communication channels between the organism's interior and exterior. Thus, the immune system continuously evolves depending on the internal and external stimuli it encounters. Furthermore, this far-reaching network's existence implies activities resembling those of classical biological factors or activities that modulate the function of other classical biological factors. A few such antibodies have already been found. Another important concept is that natural autoantibodies are highly dependent on the presence or absence of commensal microbes in the organism. These results are in line with past and recent findings showing the fundamental influence of the microbiota on proper immune system development, and necessitate the existence of a host-microbe homeostasis. This homeostasis requires that the participating humoral and cellular receptors are able to recognize self-antigens and commensal microbes without damaging them. Autopolyreactive immune receptors expressing low affinity for both types of antigens fulfil this role. The immune system appears to play a holistic role similar to that of the nervous system. PMID- 26808311 TI - Short-Term Effects of Climatic Variables on Hand, Foot, and Mouth Disease in Mainland China, 2008-2013: A Multilevel Spatial Poisson Regression Model Accounting for Overdispersion. AB - BACKGROUND: Hand, Foot, and Mouth Disease (HFMD) is a worldwide infectious disease. In China, many provinces have reported HFMD cases, especially the south and southwest provinces. Many studies have found a strong association between the incidence of HFMD and climatic factors such as temperature, rainfall, and relative humidity. However, few studies have analyzed cluster effects between various geographical units. METHODS: The nonlinear relationships and lag effects between weekly HFMD cases and climatic variables were estimated for the period of 2008-2013 using a polynomial distributed lag model. The extra-Poisson multilevel spatial polynomial model was used to model the exact relationship between weekly HFMD incidence and climatic variables after considering cluster effects, provincial correlated structure of HFMD incidence and overdispersion. The smoothing spline methods were used to detect threshold effects between climatic factors and HFMD incidence. RESULTS: The HFMD incidence spatial heterogeneity distributed among provinces, and the scale measurement of overdispersion was 548.077. After controlling for long-term trends, spatial heterogeneity and overdispersion, temperature was highly associated with HFMD incidence. Weekly average temperature and weekly temperature difference approximate inverse "V" shape and "V" shape relationships associated with HFMD incidence. The lag effects for weekly average temperature and weekly temperature difference were 3 weeks and 2 weeks. High spatial correlated HFMD incidence were detected in northern, central and southern province. Temperature can be used to explain most of variation of HFMD incidence in southern and northeastern provinces. After adjustment for temperature, eastern and Northern provinces still had high variation HFMD incidence. CONCLUSION: We found a relatively strong association between weekly HFMD incidence and weekly average temperature. The association between the HFMD incidence and climatic variables spatial heterogeneity distributed across provinces. Future research should explore the risk factors that cause spatial correlated structure or high variation of HFMD incidence which can be explained by temperature. When analyzing association between HFMD incidence and climatic variables, spatial heterogeneity among provinces should be evaluated. Moreover, the extra-Poisson multilevel model was capable of modeling the association between overdispersion of HFMD incidence and climatic variables. PMID- 26808312 TI - Sphingosine kinase 2 deficient mice exhibit reduced experimental autoimmune encephalomyelitis: Resistance to FTY720 but not ST-968 treatments. AB - The immunomodulatory drug FTY720 is presently approved for the treatment of relapsing-remitting multiple sclerosis. It is a prodrug that requires activation by sphingosine kinase 2 (SK-2) to induce T cell homing to secondary lymphoid tissue. In this study, we have investigated the role of SK-2 in experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. We show that SK-2 deficiency reduced clinical symptoms of EAE. Furthermore, in SK-2-deficient mice, the protective effect of FTY720 on EAE was abolished, while the non-prodrug FTY720 derivative ST-968 was still fully active. Protection was paralleled by reduced numbers of T-lymphocytes in blood and a reduced blood-brain-barrier leakage. This correlated with reduced mRNA expression of ICAM-1, VCAM-1, but enhanced expression of PECAM-1. A similar regulation of permeability and of PECAM-1 was seen in primary cultures of isolated mouse brain vascular endothelial cells and in a human immortalized cell line upon SK-2 knockdown. In summary, these data demonstrated that deletion of SK-2 exerts a protective effect on the pathogenesis of EAE in C57BL/6 mice and that SK-2 is essential for the protective effect of FTY720 but not of ST-968. Thus, ST-968 is a promising novel immunomodulatory compound that may be a valuable alternative to FTY720 under conditions where SK-2 activity is limited. PMID- 26808313 TI - D2 dopamine receptors modulate neuronal resonance in subthalamic nucleus and cortical high-voltage spindles through HCN channels. AB - The high-voltage spindles (HVSs), one of the characteristic oscillations that include theta frequencies in the basal ganglia (BG)-cortical system, are involved in immobile behavior and show increasing power in Parkinson's disease (PD). Our previous results suggested that the D2 dopamine receptor might be involved in HVSs modulations in a rat model of PD. Membrane resonance is one of the cellular mechanisms of network oscillation; therefore, we investigated how dopamine modulates the theta frequency membrane resonance of neurons in the subthalamic nucleus (STN), a central pacemaker of BG, and whether such changes in STN neurons subsequently alter HVSs in the BG-cortical system. In particular, we tested whether dopamine modulates HVSs through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels-dependent membrane resonance in STN neurons. We found that an antagonist of D2 receptors, but not of D1 receptors, inhibited membrane resonance and HCN currents of STN neurons through a G-protein activity in acute brain slices. Our further in vivo experiments using local injection of a D2 receptor antagonist or an HCN blocker in STNs of free-moving rats showed an increase in HVSs power and correlation in the BG-cortical system. Local injection of lamotrigine, an HCN agonist, counteracted the effect induced by the D2 antagonist. Taken together, our results revealed a potential cellular mechanism underlying HVSs activity modulation in the BG-cortical system, i.e. tuning HCN activities in STN neurons through dopamine D2 receptors. Our findings might lead to a new direction in PD treatment by providing promising new drug targets for HVSs activity modulation. PMID- 26808314 TI - Early adolescent nicotine exposure affects later-life cocaine reward in mice. AB - Adolescence represents a unique developmental period associated with increased risk-taking behavior and experimentation with drugs of abuse, in particular nicotine. We hypothesized that exposure to nicotine during early adolescence might increase the risk for drug reward in adulthood. To test this hypothesis, male ICR mice were treated with a subchronic regimen of nicotine or saline during adolescence, and their preference for cocaine, morphine and amphetamine was examined using the conditioned place preference (CPP) test in adulthood. Long term behavioral changes induced by nicotine suggested a possible role of altered gene transcription. Thus, immunoblot for DeltaFosB, a member of the Fos family of transcription factors, was conducted in the nucleus accumbens of these mice. Mice treated with nicotine during early but not late adolescence showed an increase in CPP for cocaine, morphine and amphetamine later in adulthood. This effect was not seen in mice pretreated with a subchronic regimen of nicotine as adults, suggesting that exposure to nicotine specifically during early adolescence increases the rewarding effects of other drugs in adulthood. However, adolescent nicotine exposure did not alter highly palatable food conditioning in mice. The enhancement of cocaine CPP by nicotine was strain-dependent and was blocked by pretreatment with nicotinic antagonists. In addition, nicotine exposure during early adolescence induced DeltaFosB expression to a greater extent than identical nicotine exposure in adulthood, and enhanced cocaine-induced locomotor sensitization later in adulthood. These results suggest that nicotine exposure during early adolescence increases drug-induced reward in adulthood through mechanisms that may involve the induction of DeltaFosB. PMID- 26808315 TI - Nicotinic acetylcholine receptor-mediated GABAergic inputs to cholinergic interneurons in the striosomes and the matrix compartments of the mouse striatum. AB - The striatum consists of two neurochemically distinct compartments: the striosomes (or patches) and the extrastriosomal matrix. Although striatal neurons are strongly innervated by intrinsic cholinergic interneurons, acetylcholinesterase is expressed more abundantly in the matrix than in the striosomes. At present, little is known about the different cholinergic functions of the striatal compartments. In this study, we examined gamma-aminobutyric acidergic (GABAergic) inputs to cholinergic interneurons in both compartments. We found that nicotinic receptor-mediated GABAergic responses were evoked more frequently in the matrix than in the striosomes. Furthermore, a single action potential of cholinergic neurons induced nicotinic receptor-mediated GABAergic inputs to the cholinergic neurons themselves, suggesting mutual connections that shape the temporal firing pattern of cholinergic neurons. The nicotinic receptor mediated GABAergic responses were attenuated by continuous application of acetylcholine or the acetylcholinesterase inhibitor eserine and were enhanced by desformylflustrabromine, a positive allosteric modulator of the alpha4beta2 subunit containing a nicotinic receptor. These results suggest that the nicotinic impact on the GABAergic responses are not uniform despite the massive and continuous cholinergic innervation. It has been reported that differential activation of neurons in the striosomes and the matrix produce a repetitive behavior called stereotypy. Drugs acting on alpha4beta2 nicotinic receptors might provide potential tools for moderating the imbalanced activities between the compartments. PMID- 26808316 TI - Parity modifies the effects of fluoxetine and corticosterone on behavior, stress reactivity, and hippocampal neurogenesis. AB - The postpartum confers considerable risk for developing depression. Depressed patients have elevated cortisol concentrations and impaired hypothalamic pituitary-adrenal (HPA) axis negative feedback. Chronic stress or corticosterone (CORT) induces a depressive-like phenotype in rodents, including during the postpartum. The present study examined whether nulliparous and postpartum rats were differentially vulnerable to chronic high CORT and whether fluoxetine (FLX) would differentially alter the brain, behavior, and neuroendocrine function depending on reproductive experience. Nulliparous and postpartum female Sprague Dawley rats were divided into 4 groups that received 21 d of injections of CORT or oil plus FLX or saline. CORT reduced maternal behaviors whereas FLX reversed CORT-induced decreases in maternal care. CORT increased immobility in the forced swim test (FST), but FLX did not significantly alter immobility in either nulliparous or postpartum rats. Dams spent less time immobile and had lower CORT concentrations after the FST compared with nulliparae, indicating that aspects of the postpartum period may provide resilience against a depressive-like phenotype. Both CORT and parity reduced neurogenesis (doublecortin expression) in the dentate gyrus. FLX-treated rats had lower CORT concentrations following the FST and more immature neurons, but only in the nulliparous, and not postpartum, groups. These data suggest that the postpartum may inherently protect against some deleterious effects of high CORT but also confer resistance to the neurogenic and endocrine effects of FLX. Our findings are important for understanding how females in different reproductive states respond to glucocorticoids and antidepressants. PMID- 26808318 TI - Effect of Marine-Derived n-3 Polyunsaturated Fatty Acids on Major Eicosanoids: A Systematic Review and Meta-Analysis from 18 Randomized Controlled Trials. AB - BACKGROUND: Marine-derived n-3 polyunsaturated fatty acids (PUFA) may have a beneficial effect on inflammation via lowering pro-inflammatory eicosanoid concentrations. We aimed to assess the effect of marine-derived n-3 PUFA on prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and leukotriene B4 (LTB4) through systematic review and meta-analysis of randomized controlled trials. METHOD AND FINDINGS: A structured search strategy on PubMed, Web of Science and Cochrane up to November 2015 was undertaken in this meta-analysis. Standard mean difference was used to calculate the effect size of marine-derived n-3 PUFA on PGE2, TXB2 and LTB4 in a random-effect model. A total of 18 RCTs with 826 subjects were included in this systematic review and meta-analysis. Supplementation of marine derived n-3 PUFA significantly decreased concentrations of TXB2 in serum/plasma in subjects with high risk of cardiovascular diseases (SMD:-1.26; 95% CI: -1.65, 0.86) and LTB4 in neutrophils in unhealthy subjects (subjects with non-autoimmune chronic diseases or auto-immune diseases) (SMD:-0.59: 95% CI: -1.02, -0.16). Subgroup analyses showed a significant reduction of LTB4 in subjects with rheumatoid arthritis (SMD: -0.83; 95% CI: -1.37, -0.29), but not in non autoimmune chronic disease patients (SMD: -0.33; 95% CI: -0.97, 0.31). No significant publication bias was shown in the meta-analysis. CONCLUSIONS: Marine derived n-3 PUFA had a beneficial effect on reducing the concentration of TXB2 in blood of subjects with high risk of CVD as well as LTB4 in neutrophils in unhealthy subjects, and that subjects with RA showed lower LTB4 content with supplementation of marine-derived n-3 PUFA. PMID- 26808317 TI - Panethnic Differences in Blood Pressure in Europe: A Systematic Review and Meta Analysis. AB - BACKGROUND: People of Sub Saharan Africa (SSA) and South Asians(SA) ethnic minorities living in Europe have higher risk of stroke than native Europeans(EU). Study objective is to provide an assessment of gender specific absolute differences in office systolic(SBP) and diastolic(DBP) blood pressure(BP) levels between SSA, SA, and EU. METHODS AND FINDINGS: We performed a systematic review and meta-analysis of observational studies conducted in Europe that examined BP in non-selected adult SSA, SA and EU subjects. Medline, PubMed, Embase, Web of Science, and Scopus were searched from their inception through January 31st 2015, for relevant articles. Outcome measures were mean SBP and DBP differences between minorities and EU, using a random effects model and tested for heterogeneity. Twenty-one studies involving 9,070 SSA, 18,421 SA, and 130,380 EU were included. Compared with EU, SSA had higher values of both SBP (3.38 mmHg, 95% CI 1.28 to 5.48 mmHg; and 6.00 mmHg, 95% CI 2.22 to 9.78 in men and women respectively) and DBP (3.29 mmHg, 95% CI 1.80 to 4.78; 5.35 mmHg, 95% CI 3.04 to 7.66). SA had lower SBP than EU(-4.57 mmHg, 95% CI -6.20 to -2.93; -2.97 mmHg, 95% CI -5.45 to 0.49) but similar DBP values. Meta-analysis by subgroup showed that SA originating from countries where Islam is the main religion had lower SBP and DBP values than EU. In multivariate meta-regression analyses, SBP difference between minorities and EU populations, was influenced by panethnicity and diabetes prevalence. CONCLUSIONS: 1) The higher BP in SSA is maintained over decades, suggesting limited efficacy of prevention strategies in such group in Europe;2) The lower BP in Muslim populations suggests that yet untapped lifestyle and behavioral habits may reveal advantages towards the development of hypertension;3) The additive effect of diabetes, emphasizes the need of new strategies for the control of hypertension in groups at high prevalence of diabetes. PMID- 26808320 TI - Comparing transaxillary robotic thyroidectomy with conventional surgery in a UK population: A case control study. AB - INTRODUCTION: Transaxillary robotic thyroid surgery was pioneered in South Korea where cultural factors, anthropometry and remuneration favour this. Small thyroid nodules account for the majority of cases due to a national thyroid cancer screening programme. However, the technique has not been evaluated in the United Kingdom where larger thyroid nodules tend to undergo surgery in a patient population with a higher body mass index (BMI). METHODS: Long term prospective non-randomised study. Sixteen consecutive robotic hemithyroidectomy patients were compared to 16 open controls. RESULTS: There were no robotic conversions to open and no significant difference regarding pain, voice, or quality of life (QoL). In the robotic group, long term. scar cosmesis at 3 years was superior (p = 0.02) although the operative time was significantly longer (228 min vs. 85 min, p = 0.01). One patient had a transient recurrent laryngeal nerve paresis and another had temporary shoulder dysfunction. Both resolved in 4 weeks. DISCUSSION: This study highlights the considerable difference between a Western patient population compared to South East Asia. Despite this robotic thyroidectomy is feasible and safe in a UK population. CONCLUSIONS: Despite a low uptake in the UK compared to the Far East, robotic thyroidectomy represents a viable option for selected patients, achieving superior cosmesis compared with conventional thyroidectomy at the expense of time and cost. The key is careful patient selection. A randomised study is needed to establish the clinical efficacy compared to conventional surgery in this population. PMID- 26808321 TI - Antimicrobial treatment after laparoscopic appendectomy for preventing a post operative intraabdominal abscess: A Prospective Cohort Study of 1817 patients. AB - INTRODUCTION: Post-operative antimicrobial treatment is usually administered to prevent a post-operative intraabdominal abscess (IAA) after laparoscopic appendectomy (LA). The aim of this study was to identify the role of post operative antibiotic treatment and the optimal length for the antibiotic course to prevent post-operative IAA after LA. METHODS: Between January 2010 and December 2013, 1817 patients who underwent three-port LA were enrolled in this study. Patients were classified into four groups according to the type of appendicitis and infectious source control. The characteristics of antimicrobial treatment and the incidence of IAA were analyzed and compared among the four groups. RESULTS: The incidence of IAA after three-port LA was 1.5% (27/1817). The mean durations of post-operative antibiotic use were 3.1 days for the non-IAA group and 3.3 days for the IAA group, with no significant difference between the groups (p = 0.510). DISCUSSION: The length of post-operative antibiotic treatment and antimicrobial combination therapy did not affect the development of IAA, and prolonged antibiotic treatment did not prevent IAA. However, when source control was not completely achieved, an IAA was frequently observed in the patient group that received a short course of antibiotic treatment. CONCLUSION: The role of antibiotic treatment for preventing post-appendectomy IAA seems to be related with achieving intraperitoneal infectious source control. In the setting of incomplete source control, we recommend a 5-day course of antimicrobial combination therapy and consecutive source control such as peritoneal drainage. PMID- 26808322 TI - Does elective parathyroidectomy for primary hyperparathyroidism affect renal function? A prospective cohort study. AB - INTRODUCTION: Major surgery is associated with acute kidney injury (AKI). This study examines associations between elective parathyroid surgery and post operative renal impairment. METHODS: Consecutive patients undergoing elective parathyroidectomy were evaluated, and demographic data and relevant blood parameters collected. A renal risk score was calculated for each patient based on locally agreed criteria. RESULTS: 62 patients were evaluated. Mean +/- standard deviation creatinine increased between pre-operative and day 1 post-operative (72 +/- 19 vs. 76 +/- 20 MUmol/L; p < 0.010). Mean eGFR reduced between baseline and day 1 (78 +/- 15 vs. 75 +/- 16; p < 0.010) and baseline and follow-up (78 +/- 15 vs. 73 +/- 17; p < 0.050). 19 patients (30.7%) had a creatinine increase of >=10% on day 1 post-operatively and 7 (11.3%) a rise of >20%. At follow-up, 14 (30.4% of 46 patients with follow up creatinine measurements) and 5 (10.9%) patients had a creatinine of >10% and >20% higher than pre-operative or day 1 values respectively. Those with an increase in serum creatinine of >=10% (at any time point) had a greater renal risk score [median 2 (inter-quartile range, IQR 0-3) vs. 1 (0-2); p = 0.040]. CONCLUSION: A significant minority of patients undergoing elective parathyroid surgery demonstrate worsening renal function post operatively. A pre-operative risk stratification tool may identify those at risk in the clinical setting. PMID- 26808319 TI - Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer. AB - The head and neck squamous cell carcinoma (HNSCC) transcriptome has been profiled extensively, nevertheless, identifying biomarkers that are clinically relevant and thereby with translational benefit, has been a major challenge. The objective of this study was to use a meta-analysis based approach to catalog candidate biomarkers with high potential for clinical application in HNSCC. Data from publically available microarray series (N = 20) profiled using Agilent (4X44K G4112F) and Affymetrix (HGU133A, U133A_2, U133Plus 2) platforms was downloaded and analyzed in a platform/chip-specific manner (GeneSpring software v12.5, Agilent, USA). Principal Component Analysis (PCA) and clustering analysis was carried out iteratively for segregating outliers; 140 normal and 277 tumor samples from 15 series were included in the final analysis. The analyses identified 181 differentially expressed, concordant and statistically significant genes; STRING analysis revealed interactions between 122 of them, with two major gene clusters connected by multiple nodes (MYC, FOS and HSPA4). Validation in the HNSCC-specific database (N = 528) in The Cancer Genome Atlas (TCGA) identified a panel (ECT2, ANO1, TP63, FADD, EXT1, NCBP2) that was altered in 30% of the samples. Validation in treatment naive (Group I; N = 12) and post treatment (Group II; N = 12) patients identified 8 genes significantly associated with the disease (Area under curve>0.6). Correlation with recurrence/re-recurrence showed ANO1 had highest efficacy (sensitivity: 0.8, specificity: 0.6) to predict failure in Group I. UBE2V2, PLAC8, FADD and TTK showed high sensitivity (1.00) in Group I while UBE2V2 and CRYM were highly sensitive (>0.8) in predicting re-recurrence in Group II. Further, TCGA analysis showed that ANO1 and FADD, located at 11q13, were co-expressed at transcript level and significantly associated with overall and disease-free survival (p<0.05). The meta-analysis approach adopted in this study has identified candidate markers correlated with disease outcome in HNSCC; further validation in a larger cohort of patients will establish their clinical relevance. PMID- 26808323 TI - Complications of bariatric surgery: Presentation and emergency management. AB - The epidemic in obesity has led to an increase in number of so called bariatric procedures. Doctors are less comfortable managing an obese patient after bariatric surgery. Peri-operative mortality is less than 1%. The specific feature in the obese patient is that the classical signs of peritoneal irritation are never present as there is no abdominal wall and therefore no guarding or rigidity. Simple post-operative tachycardia in obese patients should be taken seriously as it is a WARNING SIGNAL. The most common complication after surgery is peritonitis due to anastomotic fistula formation. This occurs typically as an early complication within the first 10 days post-operatively and has an incidence of 1-6% after gastric bypass and 3-7% after sleeve gastrectomy. Post-operative malnutrition is extremely rare after restrictive surgery (ring, sleeve gastrectomy) although may occur after malabsorbative surgery (bypass, biliary pancreatic shunt) and is due to the restriction and change in absorption. Prophylactic cholecystectomy is not routinely carried out during the same procedure as the bypass. Superior mesenteric vein thrombosis after bariatric surgery is a diagnosis which should be considered in the presence of any postoperative abdominal pain. Initially a first etiological assessment is performed (measurement of antithrombin III and of protein C and protein S, testing for activated protein C resistance). If the least doubt is present, a medical or surgical consultation should be requested with a specialist practitioner in the management of obese patients as death rates increase with delayed diagnosis. PMID- 26808324 TI - Laparoscopic adjustable gastric band removal and outcome of subsequent revisional bariatric procedures: A retrospective review of 214 consecutive patients. AB - BACKGROUND: Laparoscopic adjustable gastric band (LAGB) removal is required in cases of slippage, erosion, infection, intolerance, or failure in weight loss. The aim of the study was to follow up the patients who underwent band removal and analyze the outcome of subsequent revisional bariatric procedures. PATIENTS AND METHODS: A retrospective review of consecutive patients who underwent LAGB removal during 3.5 years. All patients underwent a phone interview in early 2015. Patients were divided to three groups following band removal: without additional surgery, laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en Y gastric bypass (LRYGB), and Redo LAGB(Re-LAGB). Outcome of different revisional procedures was compared according to causes and symptoms before band removal, patient satisfaction, weight loss, quality of life (QOL) questionnaire, and the bariatric analysis and reporting outcome system II (BAROSII) score. RESULTS: Overall 214 patients (73.8% females) with mean age of 41.9 years were enrolled in the study. The mean time between LAGB placement and removal was 81.0 months. Mean % estimated weight loss (%EWL) was 29.6 at time of band removal. There was no difference between groups in patient age, gender, BMI before LAGB, and most co morbidities. Patients with 1-5 outpatient visits preferred additional surgery. Patients suffering from vomiting from 1 to 10 times per week preferred revision as LSG or LRYGB. Patients with lower BAROS score underwent LSG or LRYGB. Most of the patients with band intolerance underwent conversion to another bariatric procedure, while patients with band erosion and infected band preferred Re-LAGB. Most of the patients without band gained weight. There was a significant improvement in %EWL (39.9 vs 29.6), QOL (1.08 vs 0.07), and BAROS(2.82 vs-0.11) in patients who underwent additional bariatric surgery before and after band removal irrespective of surgery type. CONCLUSIONS: Patient selection for different revisional bariatric procedures after LAGB removal is a main point for surgery success. This results in high patient satisfaction, EWL, and QOL. All options (Re-LAGB, LSG, LRYGB) are feasible and safe. PMID- 26808325 TI - CT scan findings do not predict outcome of nonoperative management in small bowel obstruction: Retrospective analysis of 108 consecutive patients. AB - OBJECTIVES: The study purpose was to investigate the ability of Emergency Department CT scan to predict the need for operative intervention in patients hospitalized for small bowel obstruction (SBO) likely secondary to adhesions (ASBO) and initially managed nonoperatively. DESIGN: Retrospective case series. Statistical analysis was done with independent-samples t-test and chi-square to identify correlation between variables and outcome of nonoperative management. SETTING: Tertiary care academic medical center. PATIENTS AND METHODS: Of 200 consecutive patients hospitalized for SBO, 108 were included in the study with a diagnosis of ASBO and received initial nonoperative management. Exclusion criteria were need for emergency surgery (e.g. peritonitis) or other diagnoses (e.g. neoplasms, hernias, Crohn's disease). CT findings such as transition point, small bowel faeces, high grade obstruction, and abnormal vascular course were correlated with failure of nonoperative management. RESULTS: Only 18 patients (16.7%) required operative intervention, while the other 90 (83.3%) were successfully discharged after nonoperative care. There was no correlation between CT scan findings and treatment outcome. CONCLUSIONS: Emergency Department CT scan findings do not significantly alter management decisions in patients admitted for ASBO and managed initially with nonoperative care. PMID- 26808326 TI - A Comprehensive Behavioral Test Battery to Assess Learning and Memory in 129S6/Tg2576 Mice. AB - Transgenic Tg2576 mice overexpressing human amyloid precursor protein (hAPP) are a widely used Alzheimer's disease (AD) mouse model to evaluate treatment effects on amyloid beta (Abeta) pathology and cognition. Tg2576 mice on a B6;SJL background strain carry a recessive rd1 mutation that leads to early retinal degeneration and visual impairment in homozygous carriers. This can impair performance in behavioral tests that rely on visual cues, and thus, affect study results. Therefore, B6;SJL/Tg2576 mice were systematically backcrossed with 129S6/SvEvTac mice resulting in 129S6/Tg2576 mice that lack the rd1 mutation. 129S6/Tg2576 mice do not develop retinal degeneration but still show Abeta accumulation in the brain that is comparable to the original B6;SJL/Tg2576 mouse. However, comprehensive studies on cognitive decline in 129S6/Tg2576 mice are limited. In this study, we used two dementia mouse models on a 129S6 background- scopolamine-treated 129S6/SvEvTac mice (3-5 month-old) and transgenic 129S6/Tg2576 mice (11-13 month-old)-to establish a behavioral test battery for assessing learning and memory. The test battery consisted of five tests to evaluate different aspects of cognitive impairment: a Y-Maze forced alternation task, a novel object recognition test, the Morris water maze, the radial arm water maze, and a Y-maze spontaneous alternation task. We first established this behavioral test battery with the scopolamine-induced dementia model using 129S6/SvEvTac mice and then evaluated 129S6/Tg2576 mice using the same testing protocol. Both models showed distinctive patterns of cognitive impairment. Together, the non-invasive behavioral test battery presented here allows detecting cognitive impairment in scopolamine-treated 129S6/SvEvTac mice and in transgenic 129S6/Tg2576 mice. Due to the modular nature of this test battery, more behavioral tests, e.g. invasive assays to gain additional cognitive information, can easily be added. PMID- 26808327 TI - 1,1'-Carbonyldiimidazole (CDI) Mediated Coupling and Cyclization To Generate [1,2,4]Triazolo[4,3-a]pyridines. AB - An operationally efficient CDI mediated tandem coupling and cyclization reaction to generate [1,2,4]triazolo[4,3-a]pyridines has been reported. The reaction conditions and scope were investigated, and the methodology was demonstrated in batch mode as well as in a continuous process. PMID- 26808328 TI - Aging of Transition Metal Dichalcogenide Monolayers. AB - Two-dimensional sheets of transition metal dichalcogenides are an emerging class of atomically thin semiconductors that are considered to be "air-stable", similar to graphene. Here we report that, contrary to current understanding, chemical vapor deposited transition metal dichalcogenide monolayers exhibit poor long-term stability in air. After room-temperature exposure to the environment for several months, monolayers of molybdenum disulfide and tungsten disulfide undergo dramatic aging effects including extensive cracking, changes in morphology, and severe quenching of the direct gap photoluminescence. X-ray photoelectron and Auger electron spectroscopy reveal that this effect is related to gradual oxidation along the grain boundaries and the adsorption of organic contaminants. These results highlight important challenges associated with the utilization of transition metal dichalcogenide monolayers in electronic and optoelectronic devices. We also demonstrate a potential solution to this problem, featuring encapsulation of the monolayer sheet by a 10-20 nm thick optically transparent polymer (parylene C). This strategy is shown to successfully prevent the degradation of the monolayer material under accelerated aging (i.e., high temperature, oxygen-rich) conditions. PMID- 26808329 TI - Evaluation of Suitable Internal Control Genes for RT-qPCR in Yak Mammary Tissue during the Lactation Cycle. AB - The yak is primarily found throughout the Tibetan high plateau and the surrounding mountainous area of south central Asia; among its others attributes, its milk is very important for the local population. A key concern in the field of yak research is the better understanding of which genes control the production and composition of milk. The most accurate and sensitive method for gene expression analysis is quantitative reverse transcription polymerase chain reaction (RT-qPCR). It is essential for reliable RT-qPCR to be able to the normalize the data using internal control genes (ICGs). However, it is critical to assess the reliability of the normalization by testing multiple ICGs. Our objective was to uncover a reliable normalization for RT-qPCR data obtained from yak mammary tissue during the lactation cycle. We assessed the reliability of 10 ICGs (ACTB, EIF6, GAPDH, LRP10, MRPL39, MRPS15, MTG1, RPS8, RPS23, and UXT) using geNorm. The analysis revealed that all of the tested ICGs can be considered to be reliable, but the use of the 6 most stable ICGs should be applied to yield a reliable normalization factor (NF). We compared the results of 3 target genes (CSN1S1, ESR1, and MYC) normalized using 6, 3, or 1 of the best ICGs. We did not observe overall differences between the 3 normalization strategies with the exception of 1 time point in MYC. The use of only a single ICG is not recommended; thus, we concluded that the calculation of the NF using the 3 best ICGs, MRPS15, RPS23, and UXT, is a reliable normalization strategy for RT-qPCR data obtained from yak mammary tissue during pregnancy and lactation. A dilution effect of the ICGs due to a large increase in the mRNA of abundantly expressed genes in bovine and porcine mammary tissue during the lactation cycle was previously observed. To test for the presence of a dilution effect in our study, we evaluated the pattern of non-normalized RT-qPCR data of ICGs from pregnancy to lactation and compared them with the total RNA concentration, milk yield, and non normalized RT-qPCR data of 3 target genes. With a few exceptions, the non- normalized RT-qPCR data for the tested ICGs was significantly increased by lactation and had a positive correlation with total RNA and the non-normalized RT qPCR data of CSN1S1. These data clearly indicated the presence of a "concentration effect" of single mRNA that remains unexplained but needs to be accounted for during the normalization of RT-qPCR data. Based on our findings, we recommend that the NF of the MRPS15, RPS23, and UXT genes should be used in the normalization of RT-qPCR data obtained from mammary tissue of lactating yaks during pregnancy and lactation. PMID- 26808330 TI - Recovery of Leptospires in Short- and Medium-Term Cryopreservation Using Different Glycerol and Dimethyl Sulfoxide Concentrations. AB - Cryopreservation is a recognized method for the maintenance of Leptospira collections. Although cryoprotectants are commonly used in order to prevent or reduce the adverse effects of freezing, there is no consensus regarding the protocols of cryopreservation. This study aimed to compare cryopreservation protocols for Leptospira using different glycerol and dimethyl sulfoxide (DMSO) concentrations. Leptospira interrogans serovar Icterohaemorrhagiae, L. interrogans serovar Bratislava, and L. borgpetersenii serovar Hardjo were used as the experimental strains. For each strain, three protocols were tested using 5% and 10% glycerol and 2.5% DMSO. For each protocol, 12 tubes containing 1.5 mL of serovar were frozen at -70 degrees C on the same day. An aliquot of each serovar/protocol was thawed once a month throughout 1 year. The viability of leptospires was evaluated by the recovery of those at days 7, 14, and 21 after thawing. Although no significant difference was found among the leptospiral recovery rates for the 9 serovar/protocols tested, DMSO (2.5%) was shown to be slightly better than glycerol, and its use should be encouraged as a cryoprotectant for leptospires. PMID- 26808331 TI - Space, time, and numbers in the right posterior parietal cortex: Differences between response code associations and congruency effects. AB - The mental representations of space, time, and number magnitude are inherently linked. The right posterior parietal cortex (PPC) has been suggested to contain a general magnitude system that underlies the overlap between various perceptual dimensions. However, comparative studies including spatial, temporal, and numerical dimensions are missing. In a unified paradigm, we compared the impact of right PPC inhibition on associations with spatial response codes (i.e., Simon, SNARC, and STARC effects) and on congruency effects between space, time, and numbers. Prolonged cortical inhibition was induced by continuous theta-burst stimulation (cTBS), a protocol for transcranial magnetic stimulation (TMS), at the right intraparietal sulcus (IPS). Our results show that congruency effects, but not response code associations, are affected by right PPC inhibition, indicating different neuronal mechanisms underlying these effects. Furthermore, the results demonstrate that interactions between space and time perception are reflected in congruency effects, but not in an association between time and spatial response codes. Taken together, these results implicate that the congruency between purely perceptual dimensions is processed in PPC areas along the IPS, while the congruency between percepts and behavioral responses is independent of this region. PMID- 26808333 TI - Deep MRI brain extraction: A 3D convolutional neural network for skull stripping. AB - Brain extraction from magnetic resonance imaging (MRI) is crucial for many neuroimaging workflows. Current methods demonstrate good results on non-enhanced T1-weighted images, but struggle when confronted with other modalities and pathologically altered tissue. In this paper we present a 3D convolutional deep learning architecture to address these shortcomings. In contrast to existing methods, we are not limited to non-enhanced T1w images. When trained appropriately, our approach handles an arbitrary number of modalities including contrast-enhanced scans. Its applicability to MRI data, comprising four channels: non-enhanced and contrast-enhanced T1w, T2w and FLAIR contrasts, is demonstrated on a challenging clinical data set containing brain tumors (N=53), where our approach significantly outperforms six commonly used tools with a mean Dice score of 95.19. Further, the proposed method at least matches state-of-the-art performance as demonstrated on three publicly available data sets: IBSR, LPBA40 and OASIS, totaling N=135 volumes. For the IBSR (96.32) and LPBA40 (96.96) data set the convolutional neuronal network (CNN) obtains the highest average Dice scores, albeit not being significantly different from the second best performing method. For the OASIS data the second best Dice (95.02) results are achieved, with no statistical difference in comparison to the best performing tool. For all data sets the highest average specificity measures are evaluated, whereas the sensitivity displays about average results. Adjusting the cut-off threshold for generating the binary masks from the CNN's probability output can be used to increase the sensitivity of the method. Of course, this comes at the cost of a decreased specificity and has to be decided application specific. Using an optimized GPU implementation predictions can be achieved in less than one minute. The proposed method may prove useful for large-scale studies and clinical trials. PMID- 26808332 TI - Underlying sources of cognitive-anatomical variation in multi-modal neuroimaging and cognitive testing. AB - Healthy adults have robust individual differences in neuroanatomy and cognitive ability not captured by demographics or gross morphology (Luders, Narr, Thompson, & Toga, 2009). We used a hierarchical independent component analysis (hICA) to create novel characterizations of individual differences in our participants (N=190). These components fused data across multiple cognitive tests and neuroanatomical variables. The first level contained four independent, underlying sources of phenotypic variance that predominately modeled broad relationships within types of data (e.g., "white matter," or "subcortical gray matter"), but were not reflective of traditional individual difference measures such as sex, age, or intracranial volume. After accounting for the novel individual difference measures, a second level analysis identified two underlying sources of phenotypic variation. One of these made strong, joint contributions to both the anatomical structures associated with the core fronto-parietal "rich club" network (van den Heuvel & Sporns, 2011), and to cognitive factors. These findings suggest that a hierarchical, data-driven approach is able to identify underlying sources of individual difference that contribute to cognitive-anatomical variation in healthy young adults. PMID- 26808334 TI - Flow Synthesis in Hot Water: Synthesis of the Atypical Antipsychotic Iloperidone. AB - Inductively heated steel reactors continuously perform organic transformations in water under high temperature conditions, utilizing the unique physiochemical properties of water at subcritical conditions. We demonstrated the power of this set-up in the continuous synthesis of the atypical antipsychotic drug iloperidone, in which we performed four out of five steps under aqueous conditions. PMID- 26808335 TI - Systems, not pills: The options market for antibiotics seeks to rejuvenate the antibiotic pipeline. AB - Over the past decade, there has been a growing recognition of the increasing growth of antibiotic resistant bacteria and a relative decline in the production of novel antibacterial therapies. The combination of these two forces poses a potentially grave threat to global health, in both developed and developing countries. Current market forces do not provide appropriate incentives to stimulate new antibiotic development, thus we propose a new incentive mechanism: the Options Market for Antibiotics. This mechanism, modelled on the principle of financial call options, allows payers to buy the right, in early stages of development, to purchase antibiotics at a discounted price if and when they ever make it to market approval. This paper demonstrates the effect of such a model on the expected Net Present Value of a typical antibacterial project. As part of an integrated strategy to confront the impending antibiotic crisis, the Options Market for Antibiotics may effectively stimulate corporate and public investment into antibiotic research and development. PMID- 26808336 TI - Socioeconomic inequalities in informal payments for health care: An assessment of the 'Robin Hood' hypothesis in 33 African countries. AB - In almost all African countries, informal payments are frequently made when accessing health care. Some literature suggests that the informal payment system could lead to quasi-redistribution among patients, with physicians playing a 'Robin Hood' role, subsidizing the poor at the expense of the rich. We empirically tested this assumption with data from the rounds 3 and 5 of the Afrobarometer surveys conducted in 18 and 33 African countries respectively, from 2005 to 2006 for round 3 and from 2011 to 2013 for round 5. In these surveys, nationally representative samples of people aged 18 years or more were randomly selected in each country, with sizes varying between 1048 and 2400 for round 3 and between 1190 and 2407 for round 5. We used the 'normalized' concentration index, the poor/rich gap and the odds ratio to assess the level of inequality in the payment of bribes to access care at the local public health facility and implemented two decomposition techniques to identify the contributors to the observed inequalities. We obtained that: i) the socioeconomic gradient in informal payments is in favor of the rich in almost all countries, indicating a rather regressive system; ii) this is mainly due to the socioeconomic disadvantage itself, to poor/rich differences in supply side factors like lack of medicines, absence of doctors and long waiting times, as well as regional disparities. Although essentially empirical, the paper highlights the need for African health systems to undergo substantial country-specific reforms in order to better protect the worse-off from financial risk when they seek care. PMID- 26808337 TI - Do community- and individual-level social relationships contribute to the mental health of disaster survivors?: A multilevel prospective study after the Great East Japan Earthquake. AB - Disasters greatly threaten the health and lives of people all over the world. Japan experienced severe damage following the Great East Japan Earthquake on March 11, 2011, and some survivors continue to live in prefabricated temporary housing, built collectively in damaged areas. Previous studies have shown that social relationships in such communities have the potential to protect the mental health of disaster survivors. We examined the association between survivors' social support and social participation in 2012 and their psychological distress in 2013 using the K6 scale. Self-reported questionnaires were distributed to all 15,979 households in prefabricated temporary housing in eight municipalities in Miyagi prefecture in 2012, and 19,284 adults from 9366 (58.6%) households responded. One year later, 10,880 adults responded to a follow-up survey. Multivariate multilevel linear regression analyses with multiply imputed datasets showed that survivors' psychological distress at follow-up significantly differed between communities (community-level variance [standard error] = 0.38 [0.13]). The variance was reduced to 0.25 [0.09] after considering individual demographic characteristics and psychological distress at baseline. Individual- and community level social relationships of 7.1% and 15.8%, respectively, explained the difference. After adjusting for covariates including K6 scale at baseline, individual-level social support, community-level social support, and individual level social participation were significantly associated with low psychological distress at follow-up (coefficients [95% confidence intervals] were: -0.54 [ 0.79, -0.30]; -0.43 [-0.72, -0.14]; and -0.22 [-0.40, -0.04], respectively). Community-level social participation was not significantly associated with psychological distress. The present study showed that: 1) survivors' psychological distress varied between temporary housing communities in 2013; 2) individual- and community-level social relationships contributed to the difference; and 3) individual- and community-level social relationships in 2012 were protectively associated with survivors' psychological distress in 2013. Promoting social relationships in communities after disasters might decrease disaster survivors' psychological distress. PMID- 26808338 TI - Psychological pathways from social integration to health: An examination of different demographic groups in Canada. AB - RATIONALE: The health effects of social integration have been extensively studied, yet the underlying dynamics of this relationship deserves more exploration. One of the important hypothesized pathways through which social integration affects health is psychological functioning, including a sense of belonging, personal control and generalized trust. OBJECTIVE: Using a Canadian national survey, this study explored the effect of social integration on different health outcomes via psychological pathways, while incorporating network homophily as a predictor in the model. METHODS: Five distinct demographic groups of Canadians (the Native-born Whites, Native-born visible minorities, the Aboriginal people, immigrant Whites and immigrant visible minorities) were compared on their social integration, psychological functioning, and health outcomes. Structural equation models tested the mediation effects of psychological pathways, and group differences were explored by adding interaction terms. RESULTS: The study found that visible minority immigrants were least socially integrated, and the Aboriginal people had the poorest self-reported physical and mental health. Although the Aboriginal people had large networks and active network interactions, they showed stronger ethnic and linguistic homophily in their network formation than the two visible minority groups. Structural equation model results supported the mediated relationship between social integration and health via psychological pathways. A positive effect of friendship ethnic homophily on health was identified and explored. CONCLUSION: Policy makers may seek opportunities to create social environments that facilitate social interactions and formation of social ties and provide support for programs serving ethnic and immigrant groups. PMID- 26808340 TI - Neurophysiological markers of multiple facets of impulsivity. AB - Human behavior is influenced by three core personality systems: approach, avoidance, and supervisory control. The supervisory control system is inversely related to impulsivity. Although past research has related some aspects of impulsivity to frontal hemispheric asymmetry, impulsivity as a multi-faceted construct has not been studied in relation with frontal asymmetry. In addition, past work has potentially confounded impulsivity with approach-motivation. In the current study, greater relative left frontal activity was related to multiple facets of impulsivity: negative urgency, lack of premeditation, lack of perseverance, and positive urgency. Regressing both positive and negative urgency on frontal asymmetry revealed that approach-related positive urgency related to greater left frontal activity, but withdrawal-related negative urgency marginally related to greater right frontal activity. These results suggest that impulsivity, independent of affective valence, relates to greater left frontal activity. When controlling for trait approach motivation, the relationship between impulsivity and left frontal activity is unchanged. PMID- 26808339 TI - Maternal distress and child neuroendocrine and immune regulation. AB - RATIONALE: Neuroendocrine-immune regulation is essential for maintaining health. Early-life adversity may cause dysregulation in the neuroendocrine-immune network through repeated activation of the stress response, thereby increasing disease risk. OBJECTIVE: This paper examined the extent to which maternal psychological well-being moderates neuroendocrine-immune relations in children. METHODS: We used data from a laboratory-based study of mothers and their five-year old children (n = 125 mother-child pairs) conducted from 2011 to 2013 in Baltimore, Maryland. Child saliva was assayed for markers of immune function (i.e., cytokines: interleukin [IL]-1beta, IL-6, IL-8, tumor necrosis factor alpha [TNF alpha]) and hypothalamic-pituitary-adrenal activity (i.e., cortisol). A composite score for depressive symptoms, anxiety, and parenting stress characterized maternal psychological distress. Multilevel mixed models examined the relationship between maternal psychological well-being and child neuroendocrine immune relations. RESULTS: Significant cytokine * maternal distress interactions indicated that as maternal distress increased, expected inverse cytokine-cortisol relations within children became weaker for IL-1beta, IL-6, and TNF-alpha. Sex stratified models revealed that these interactions were only significant among girls. Among boys, there were inverse cytokine-cortisol relations for all cytokines, and, while in the same direction as observed among girls, the cytokine * maternal distress interactions were non-significant. CONCLUSION: The findings suggest that maternal distress is associated with child neuroendocrine-immune relations in saliva and may alter the sensitivity of inflammatory immune processes to cortisol's inhibitory effects. This desensitization may place the child at risk for inflammatory diseases. The findings support efforts for the early detection and treatment of at-risk mothers to protect maternal and child health and well-being. PMID- 26808341 TI - Liquid Crystal Droplet-Embedded Biopolymer Hydrogel Sheets for Biosensor Applications. AB - The development of simple, portable, and low-cost biosensing platforms is of great interest in the clinical diagnosis of disease. Here, we report liquid crystal (LC) droplet-embedded chitosan (CHI) hydrogel films formed by the Ag(+) ion-triggered fast gelation of the CHI/surfactant complex-stabilized LC emulsion which is cast on substrates. The small sheets cut from the LC droplet-embedded hydrogel films combine the advantages of both hydrogels and LC droplets, offering a portable and label-free sensing platform for the real-time detection of bile acids in a small amount of solution. We find that the response time and detection limit of LC droplet-embedded hydrogel sheets for bile acids depend on their chemical structures. PMID- 26808342 TI - Cancer statistics in China, 2015. AB - With increasing incidence and mortality, cancer is the leading cause of death in China and is a major public health problem. Because of China's massive population (1.37 billion), previous national incidence and mortality estimates have been limited to small samples of the population using data from the 1990s or based on a specific year. With high-quality data from an additional number of population based registries now available through the National Central Cancer Registry of China, the authors analyzed data from 72 local, population-based cancer registries (2009-2011), representing 6.5% of the population, to estimate the number of new cases and cancer deaths for 2015. Data from 22 registries were used for trend analyses (2000-2011). The results indicated that an estimated 4292,000 new cancer cases and 2814,000 cancer deaths would occur in China in 2015, with lung cancer being the most common incident cancer and the leading cause of cancer death. Stomach, esophageal, and liver cancers were also commonly diagnosed and were identified as leading causes of cancer death. Residents of rural areas had significantly higher age-standardized (Segi population) incidence and mortality rates for all cancers combined than urban residents (213.6 per 100,000 vs 191.5 per 100,000 for incidence; 149.0 per 100,000 vs 109.5 per 100,000 for mortality, respectively). For all cancers combined, the incidence rates were stable during 2000 through 2011 for males (+0.2% per year; P = .1), whereas they increased significantly (+2.2% per year; P < .05) among females. In contrast, the mortality rates since 2006 have decreased significantly for both males (-1.4% per year; P < .05) and females (-1.1% per year; P < .05). Many of the estimated cancer cases and deaths can be prevented through reducing the prevalence of risk factors, while increasing the effectiveness of clinical care delivery, particularly for those living in rural areas and in disadvantaged populations. PMID- 26808344 TI - A mechanism for the hole-mediated water photooxidation on TiO2 (1 0 1) surfaces. AB - The mechanism of water photooxidation on TiO2 surfaces is still controversial. Here we report a first-principles density functional study based on a hybrid functional method in which an adsorbed water molecule is found to directly interact with a self-trapped hole at a bridging oxygen site and to transform into an OH(*) radical species through a concerted proton/hole transfer. This study analyzes both the thermodynamics and kinetics of this step of the reaction, which is generally considered to be the rate determining one. The fate of the OH(*) radical is then investigated in terms of its reactivity with different surface species, with a second OH(*) radical, or with a second water molecule coming from the environment. We find that OH(*) radicals can either acquire a hydrogen from surrounding water molecules or, if they meet, couple to form hydrogen peroxide with highly associated energy gain. PMID- 26808343 TI - Intact recognition, but attenuated adaptation, for biological motion in youth with autism spectrum disorder. AB - Given the ecological importance of biological motion and its relevance to social cognition, considerable effort has been devoted over the past decade to studying biological motion perception in autism. However, previous studies have asked observers to detect or recognize briefly presented human actions placed in isolation, without spatial or temporal context. Research on typical populations has shown the influence of temporal context in biological motion perception: prolonged exposure to one action gives rise to an aftereffect that biases perception of a subsequently displayed action. Whether people with autism spectrum disorders (ASD) show such adaptation effects for biological motion stimuli remains unknown. To address this question, this study examined how well youth with ASD recognize ambiguous actions and adapt to recently-observed actions. Compared to typically-developing (TD) controls, youth with ASD showed no differences in perceptual boundaries between actions categories, indicating intact ability in recognizing actions. However, children with ASD showed weakened adaptation to biological motion. It is unlikely that the reduced action adaptability in autism was due to delayed developmental trajectory, as older children with ASD showed weaker adaptation to actions than younger children with ASD. Our results further suggest that high-level (i.e., action) processing weakens with age for children with ASD, but this change may be accompanied by a potentially compensatory mechanism based on more involvement of low-level (i.e., motion) processing. Autism Res 2016, 9: 1103-1113. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 26808345 TI - A ball-bearing structured triboelectric nanogenerator for nondestructive damage and rotating speed measurement. AB - A ball-bearing structure based triboelectric nanogenerator (B-TENG) with interdigitative-electrodes was developed that can not only collect energy from rotational kinetic energy, but also serve as a self-powered and multifunctional sensor. The B-TENG relies on the rolling electrification between PTFE balls on Cu interdigitative-electrodes, which delivers an open-circuit voltage of ~40 V and a short-circuit current of ~1.2 MUA at a rotating speed of 300 rpm for 4 mm PTFE balls. Using the output signals of B-TENG, a nondestructive detection for the damage of PTFE balls was realized without demounting the bearing. Besides, based on the periodic signals produced from B-TENG, the rotation speed of ball-bearing can be obtained according to the time difference between several cycles. PMID- 26808346 TI - Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. AB - The transplantation of glucose-responsive, insulin-producing cells offers the potential for restoring glycemic control in individuals with diabetes. Pancreas transplantation and the infusion of cadaveric islets are currently implemented clinically, but these approaches are limited by the adverse effects of immunosuppressive therapy over the lifetime of the recipient and the limited supply of donor tissue. The latter concern may be addressed by recently described glucose-responsive mature beta cells that are derived from human embryonic stem cells (referred to as SC-beta cells), which may represent an unlimited source of human cells for pancreas replacement therapy. Strategies to address the immunosuppression concerns include immunoisolation of insulin-producing cells with porous biomaterials that function as an immune barrier. However, clinical implementation has been challenging because of host immune responses to the implant materials. Here we report the first long-term glycemic correction of a diabetic, immunocompetent animal model using human SC-beta cells. SC-beta cells were encapsulated with alginate derivatives capable of mitigating foreign-body responses in vivo and implanted into the intraperitoneal space of C57BL/6J mice treated with streptozotocin, which is an animal model for chemically induced type 1 diabetes. These implants induced glycemic correction without any immunosuppression until their removal at 174 d after implantation. Human C peptide concentrations and in vivo glucose responsiveness demonstrated therapeutically relevant glycemic control. Implants retrieved after 174 d contained viable insulin-producing cells. PMID- 26808347 TI - Rescue of GABAB and GIRK function in the lateral habenula by protein phosphatase 2A inhibition ameliorates depression-like phenotypes in mice. AB - The lateral habenula (LHb) encodes aversive signals, and its aberrant activity contributes to depression-like symptoms. However, a limited understanding of the cellular mechanisms underlying LHb hyperactivity has precluded the development of pharmacological strategies to ameliorate depression-like phenotypes. Here we report that an aversive experience in mice, such as foot-shock exposure (FsE), induces LHb neuronal hyperactivity and depression-like symptoms. This occurs along with increased protein phosphatase 2A (PP2A) activity, a known regulator of GABAB receptor (GABABR) and G protein-gated inwardly rectifying potassium (GIRK) channel surface expression. Accordingly, FsE triggers GABAB1 and GIRK2 internalization, leading to rapid and persistent weakening of GABAB-activated GIRK-mediated (GABAB-GIRK) currents. Pharmacological inhibition of PP2A restores both GABAB-GIRK function and neuronal excitability. As a consequence, PP2A inhibition ameliorates depression-like symptoms after FsE and in a learned helplessness model of depression. Thus, GABAB-GIRK plasticity in the LHb represents a cellular substrate for aversive experience. Furthermore, its reversal by PP2A inhibition may provide a novel therapeutic approach to alleviate symptoms of depression in disorders that are characterized by LHb hyperactivity. PMID- 26808348 TI - Human 'brite/beige' adipocytes develop from capillary networks, and their implantation improves metabolic homeostasis in mice. AB - Uncoupling protein 1 (UCP1) is highly expressed in brown adipose tissue, where it generates heat by uncoupling electron transport from ATP production. UCP1 is also found outside classical brown adipose tissue depots, in adipocytes that are termed 'brite' (brown-in-white) or 'beige'. In humans, the presence of brite or beige (brite/beige) adipocytes is correlated with a lean, metabolically healthy phenotype, but whether a causal relationship exists is not clear. Here we report that human brite/beige adipocyte progenitors proliferate in response to pro angiogenic factors, in association with expanding capillary networks. Adipocytes formed from these progenitors transform in response to adenylate cyclase activation from being UCP1 negative to being UCP1 positive, which is a defining feature of the beige/brite phenotype, while displaying uncoupled respiration. When implanted into normal chow-fed, or into high-fat diet (HFD)-fed, glucose intolerant NOD-scid IL2rg(null) (NSG) mice, brite/beige adipocytes activated in vitro enhance systemic glucose tolerance. These adipocytes express neuroendocrine and secreted factors, including the pro-protein convertase PCSK1, which is strongly associated with human obesity. Pro-angiogenic conditions therefore drive the proliferation of human beige/brite adipocyte progenitors, and activated beige/brite adipocytes can affect systemic glucose homeostasis, potentially through a neuroendocrine mechanism. PMID- 26808349 TI - Unnecessary Use of Red Lights and Sirens in Pediatric Transport. AB - INTRODUCTION: Approximately 25.5 million pediatric patients are treated in Emergency Departments around the United States annually. Roughly 7% of these patients are transported by ambulance; of these, approximately 7% arrive in ambulances running red lights and sirens (RLS). Compared to those transporting without RLS, emergency vehicles employing RLS are involved in more accidents and are associated with more fatalities. OBJECTIVE: To characterize the use of RLS in pediatric transports and identify factors associated with unnecessary use of RLS. METHODS: As part of the Children's Safety Initiative (CSI-EMS), a large, multi phased National Institutes of Health-funded study, we conducted a medical record review of all pediatric RLS transports in an urban EMS system over a 4-year period (2008-11). A standardized chart abstraction tool was adapted for the out of-hospital setting and pilot tested. Charts were independently reviewed by physicians and paramedics, with disagreements arbitrated by a pediatric emergency physician. Reviewers were asked to judge whether RLS transport was necessary and to provide comments justifying their position. Descriptive statistics were used to measure the frequency of unnecessary transports and logistic regression analysis was employed to identify factors associated with unnecessary use of RLS. RESULTS: Of 490 RLS transports, experts identified 96 (19.6%) as unnecessary use of RLS. Necessary and unnecessary RLS transports had similar patient sex and duration of transport, though unnecessary use of RLS tended to increase with patient age. The call reasons that represented the largest proportion of unnecessary RLS transports were trauma (49.0%), respiratory distress (16.7%), and seizure/altered mental status (11.5%). Compared with necessary RLS transports, unnecessary RLS transports were less likely to require resuscitation, airway management, or medication administration. Univariate analysis revealed that patient vital signs within normal limits were associated with increased risk of unnecessary RLS transport, with the most pronounced effect seen in the normal GCS score group (odds ratio 7.74, p-value 0.001). CONCLUSIONS: This analysis identified patient and transport characteristics associated with unnecessary use of RLS. Our results could help serve as the basis for designing and prospectively evaluating protocols for use of RLS, potentially mitigating the risk associated with transport in pediatric patients. PMID- 26808350 TI - Patient injuries in primary total hip replacement. AB - Background and purpose - Although the results of primary total hip replacements (THRs) are generally excellent, sometimes serious complications arise. Some of these severe complications are considered to be patient injuries. We analyzed primary THR-related patient injuries in a nationwide setting. Patients and methods - We evaluated all the primary THR-related patient injury claims in Finland between 2008 and 2010. We used the original medical records and 2 nationwide registries, the Care Register for Social Welfare and Health Care and the Patient Injury Claim Register. Results - We identified 563 claims, 44% of which were compensated (n = 250). Of these 250 compensated claims, 79% were considered to be avoidable (treatment injuries) and 21% were severe unexpected infections (with a preoperative infection risk of less than 2%). The most common type of technical error was cup malposition (31%). High-volume hospitals (with an annual primary THR volume >= 400) had a lower patient injury rate. In lower volume hospitals (with an annual primary THR volume of < 400), the relative risks (RRs) of patient injury for any reason, due to technical errors, or because of cup malposition were 2-fold (95% CI: 1.6-3.1), 4-fold (95% CI: 2.3-6.2), and 9 fold (95% CI: 3-28), respectively, compared to high-volume hospitals. Interpretation - Our study provides the first comprehensive nationwide data on THR-related patient injury types. Hospital volume was associated with the quality and quantity of errors detected. An annual hospital volume of >= 400 primary THRs was established as a protective factor against patient injuries. PMID- 26808351 TI - Using Local States To Drive the Sampling of Global Conformations in Proteins. AB - Conformational changes associated with protein function often occur beyond the time scale currently accessible to unbiased molecular dynamics (MD) simulations, so that different approaches have been developed to accelerate their sampling. Here we investigate how the knowledge of backbone conformations preferentially adopted by protein fragments, as contained in precalculated libraries known as structural alphabets (SA), can be used to explore the landscape of protein conformations in MD simulations. We find that (a) enhancing the sampling of native local states in both metadynamics and steered MD simulations allows the recovery of global folded states in small proteins; (b) folded states can still be recovered when the amount of information on the native local states is reduced by using a low-resolution version of the SA, where states are clustered into macrostates; and (c) sequences of SA states derived from collections of structural motifs can be used to sample alternative conformations of preselected protein regions. The present findings have potential impact on several applications, ranging from protein model refinement to protein folding and design. PMID- 26808353 TI - Body image and face image in Asian American and white women: Examining associations with surveillance, construal of self, perfectionism, and sociocultural pressures. AB - Asian American women experience sociocultural pressures that could place them at increased risk for experiencing body and face dissatisfaction. Asian American and White women completed measures of appearance evaluation, overweight preoccupation, face satisfaction, face dissatisfaction frequency, perfectionism, surveillance, interdependent and independent self-construal, and perceived sociocultural pressures. In Study 1 (N=182), Asian American women were more likely than White women to report low appearance evaluation (24% vs. 12%; d= 0.50) and to be sometimes-always dissatisfied with the appearance of their eyes (38% vs. 6%; d=0.90) and face overall (59% vs. 34%; d=0.41). In Study 2 (N=488), they were more likely to report low appearance evaluation (36% vs. 23%; d=-0.31) and were less likely to report high eye appearance satisfaction (59% vs. 88%; d= 0.84). The findings highlight the importance of considering ethnic differences when assessing body and face image. PMID- 26808352 TI - Bacterial indicator taxa in soils under different long-term agricultural management. AB - AIMS: In this study, the species indicator test was used to identify key bacterial taxa affected by changes in the soil environment as a result of conservation agriculture or conventional practices. METHODS AND RESULTS: Soils cultivated with wheat (Triticum spp. L.) and maize (Zea mays L.) under different raised bed planting systems for 20 years, that is, varying crop residue and fertilizer management, were used. Taxonomic- and divergence-based 16S metagenomics, and IndVal analysis were used to study the bacterial communities and identify indicator taxa (genus and OTU97 ) affected by agricultural practices. Although, some phyla were affected significantly by different treatments, the taxonomic assemblages at phylum level were similar. Bacterial taxa related to different processes of the N-cycle were indicators of different fertilization rates, for example, Azorhizobium, Nostoc and Nitrosomonas. A large number of OTU97 were indicators for conventionally tilled beds and their distribution was defined by soil organic carbon. IndVal analysis identified different taxa in each of the residue management systems. This suggests that although the same organic material remains in the field, crop residue management affects specific taxa. The taxa indicator of the burned residues belonged mainly to the order SBR1031 (Anaerolineae, Chloroflexi), and the genera Bacillus and Alicyclobacillus. CONCLUSIONS: N-fertilizer application rates affected N-cycling taxa. Tillage affected Actinobacteria members and organic matter decomposers. Although the same crop residue was retained in the field, organic material management was important for specific taxa. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we report that agricultural practice affected soil bacterial communities. We also identified distinctive taxa and related their distribution to changes in the soil environment resulting from different agricultural practices. PMID- 26808354 TI - Pasireotide for the treatment of acromegaly. AB - INTRODUCTION: Acromegaly is a chronic disease with high morbidity and enhanced mortality if left untreated. Treatment options include surgery, medical therapy (somatostatin analogues (SA), dopamine agonists (DA) and growth hormone receptor antagonists) and radiotherapy. Despite these treatment options, "real-life" studies have shown that approximately 50% of patients are not controlled. In this scenario, a next-generation SA, pasireotide, has recently been approved for the treatment of acromegaly. AREAS COVERED: 1) pasireotide's pharmacokinetics and pharmacodynamics; 2) pasireotide's anti-secretory and anti-proliferative effects, from preclinical studies up to phase III clinical trials; and 3) the adverse effects of pasireotide, focusing on hyperglycemia; 4) biomarkers of response to SA treatment. EXPERT OPINION: surgery is the primary treatment for most patients with acromegaly; however, approximately half of them will need adjuvant therapy. At present, the decision of this adjuvant treatment is made on a "trial-and error" fashion. Nevertheless, in recent years, efforts have been made to establish biomarkers for the response to drugs involved in the treatment of acromegaly, which will change the treatment of acromegaly towards a more personalized therapeutic decision-making process. In the near future, the establishment of pasireotide response biomarkers will allow us to identify good candidates for first-line medical monotherapy with pasireotide. PMID- 26808355 TI - Role of Bismuth in the Eradication of Helicobacter pylori. AB - Bismuth salts exert their activity within the upper gastrointestinal tract through action of luminal bismuth. Bismuth exerts direct bactericidal effect on Helicobacter pylori by different ways: forms complexes in the bacterial wall and periplasmic space, inhibits different enzymes, ATP synthesis, and adherence of the bacteria to the gastric mucosa. Bismuth also helps ulcer healing by acting as a barrier to the aggressive factors and increasing mucosal protective factors such as prostaglandin, epidermal growth factor, and bicarbonate secretion. To date, no resistance to bismuth has been reported. Also synergism between bismuth salts and antibiotics was present. It was shown that metronidazole and clarithromycin resistant H. pylori strains become susceptible if they are administered together with bismuth. Bismuth-containing quadruple therapy was recommended both by the Second Asia-Pacific Consensus Guidelines and by the Maastricht IV/Florence Consensus Report as an alternative first choice regimen to standard triple therapy, in areas with low clarithromycin resistance, and it is recommended as the first-line therapeutic option in areas with a high prevalence of clarithromycin resistance. Greater than 90% eradication success can be obtained by bismuth-containing quadruple therapy. Choosing bismuth as an indispensable part of first-line therapy is logical as both metronidazole and clarithromycin resistances can be overcome by adding bismuth to the regimen. PMID- 26808356 TI - Constipation and Outcomes of Cecostomy. AB - Constipation, defined as delay or difficulty in defecation, present for 2 or more weeks, is a common problem encountered by both primary and specialty medical providers. There are no randomized controlled trials on the use of antegrade enemas in the pediatric population. Most published papers are based on the experience at a particular center. The aim of this article is to describe the pathophysiology of constipation, review the contribution of colonic manometry to the diagnosis of constipation, summarize the advancements in the management of constipation through the use of antegrade enemas, and study the outcomes of cecostomy at different centers. This study is a comprehensive literature review generated by computerized search of literature, supplemented by review of monographs and textbooks in pathology, gastroenterology, and surgery. Literature search was performed using the publications from 1997 to 2012. The search included publications of all types presenting or reviewing data on cecostomy. The antegrade continence enema is a therapeutic option for defecation disorders when maximal conventional therapy is not successful. Symptoms of defecation disorders in children with different underlying etiologies improve significantly after a cecostomy is created. In addition, there is a benefit on the patients' physical activity, healthcare utilization, and general well-being. Based on the review of published literature it seems that antegrade enemas are a successful therapeutic option in children with severe constipation and/or fecal incontinence. With the advent of cecostomy buttons, patient compliance and the overall cosmetic appearance have improved. PMID- 26808357 TI - Strategy for the Prediction of Steady-State Exposure of Digoxin to Determine Drug Drug Interaction Potential of Digoxin With Other Drugs in Digitalization Therapy. AB - Digoxin, a narrow therapeutic index drug, is widely used in congestive heart failure. However, the digitalization therapy involves dose titration and can exhibit drug-drug interaction. Ctrough versus area under the plasma concentration versus time curve in a dosing interval of 24 hours (AUC0-24h) and Cmax versus AUC0-24h for digoxin were established by linear regression. The predictions of digoxin AUC0-24h values were performed using published Ctrough or Cmax with appropriate regression lines. The fold difference, defined as the quotient of the observed/predicted AUC0-24h values, was evaluated. The mean square error and root mean square error, correlation coefficient (r), and goodness of the fold prediction were used to evaluate the models. Both Ctrough versus AUC0-24h (r = 0.9215) and Cmax versus AUC0-24h models for digoxin (r = 0.7781) showed strong correlations. Approximately 93.8% of the predicted digoxin AUC0-24h values were within 0.76-fold to 1.25-fold difference for Ctrough model. In sharp contrast, the Cmax model showed larger variability with only 51.6% of AUC0-24h predictions within 0.76-1.25-fold difference. The r value for observed versus predicted AUC0 24h for Ctrough (r = 0.9551; n = 177; P < 0.001) was superior to the Cmax (r = 0.6134; n = 275; P < 0.001) model. The mean square error and root mean square error (%) for the Ctrough model were 11.95% and 16.2% as compared to 67.17% and 42.3% obtained for the Cmax model. Simple linear regression models for Ctrough/Cmax versus AUC0-24h were derived for digoxin. On the basis of statistical evaluation, Ctrough was superior to Cmax model for the prediction of digoxin AUC0-24h and can be potentially used in a prospective setting for predicting drug-drug interaction or lack of it. PMID- 26808358 TI - Comparison of Famciclovir, Valaciclovir, and Brivudine Treatments in Adult Immunocompetent Patients With Herpes Zoster. AB - Herpes zoster (HZ) is a common disease characterized by the recurrence of varicella zoster, that stays dormant in sensory ganglia. The primary goal of this study was to compare efficiencies of famciclovir, valaciclovir, and brivudine in terms of pain relief in HZ patients. Records of patients who were admitted to the Dermatology Clinic of our hospital due to acute HZ between the years 2012 and 2014 were retrospectively analyzed. Treatment decisions were at the discretion of caring physicians as valaciclovir (VACV), famciclovir (FCV), and brivudine (BRV) based on the clinical observations. BRV, FCV, and VACV were effective in treating pain in acute HZ. There was no significant difference between mild and moderate HZ patients. In severe cases, a significant reduction in intensity of pain was observed on day 3 in the BRV group, on day 7 in the FCV group, and at 2-3 weeks in the VACV group. There were no significant side effects observed in any of the groups. Results of this study indicate that brivudine may be the first choice in severe HZ cases as it controls pain earlier and is easier to use because of its once daily administration. PMID- 26808359 TI - Standardization of a cytometric p24-capture bead-assay for the detection of main HIV-1 subtypes. AB - The prevailing method to assess HIV-1 replication and infectivity is to measure the production of p24 Gag protein by enzyme-linked immunosorbent assay (ELISA). Since fluorescent bead-based technologies offer a broader dynamic range and higher sensitivity, this study describes a p24 capture Luminex assay capable of detecting HIV-1 subtypes A-D, circulating recombinant forms (CRF) CRF01_AE and CRF02_AG, which together are responsible for over 90% of HIV-1 infections worldwide. The success of the assay lies in the identification and selection of a cross-reactive capture antibody (clone 183-H12-5C). Fifty-six isolates that belonged to six HIV-1 subtypes and CRFs were successfully detected with p-values below 0.021; limits of detection ranging from 3.7 to 3 * 104 pg/ml. The intra- and inter-assay variation gave coefficient of variations below 6 and 14%, respectively. The 183-bead Luminex assay also displayed higher sensitivity of 91% and 98% compared to commercial p24 ELISA and a previously described Luminex assay. The p24 concentrations measured by the 183-bead Luminex assay showed a significant correlation (R=0.92, p<0.0001) with the data obtained from quantitative real time PCR. This newly developed p24 assay leverages the advantages of the Luminex platform, which include smaller sample volume and simultaneous detection of up to 500 analytes in a single sample, and delivers a valuable tool for the field. PMID- 26808360 TI - CRITICAL APPRAISAL. Sleep Bruxism and Sleep-Disordered Breathing. AB - Sleep bruxism (SB) is a repetitive jaw muscle activity with clenching or grinding of the teeth during sleep. SB is characterized by what is known as rhythmic masticatory muscle activity (RMMA). RMMA is the laboratory polysomnographic finding that differentiates SB from other oromandibular movements seen during sleep. Most often RMMA episodes are associated with sleep arousal. Some patients will report similar complaints related to both SB and sleep disordered breathing (SDB). There are some reports that would suggest that SB is a result of SDB. It has has been postulated that SB is a compensatory mechanism to re establish muscle tone of the upper airway. While these disorders do in fact often present concomitantly, the relationship between the two is yet to be fully elucidated. This Critical Appraisal reviews 3 recent publications with the intent to better define what relationships may exists between SDB and SB. While the current evidence appears to support the notion that these are often concomitant disorders, it also makes clear that evidence to support the hypothesis that SDB is causative for SB is currently lacking. PMID- 26808361 TI - ALS Untangled No.33 Endotherapia. PMID- 26808362 TI - Nanosheet Formation in Hyperswollen Lyotropic Lamellar Phases. AB - Nanosheets (~1 nm) are formed using a nonionic hyperswollen lyotropic lamellar phase as a template. The accumulation and reaction of ingredients in the highly separated (several hundred nm) bilayers in the hyperswollen lyotropic lamellar phase should result in very thin nanosheets. This method could be applied to the synthesis of a wide variety of two-dimensional organic and inorganic materials. PMID- 26808363 TI - From coeliac disease to noncoeliac gluten sensitivity; should everyone be gluten free? AB - PURPOSE OF REVIEW: Gluten-free diets (GFDs) have seen a disproportional rise in use and popularity relative to the prevalence of established gluten-related disorders such as coeliac disease or immunoglobulin E wheat allergy. This entity has been termed noncoeliac gluten sensitivity (NCGS). This review aims to provide a current perspective on the emerging evidence for and against NCGS, along with the associated need for a GFD. RECENT FINDINGS: NCGS and the benefits of a GFD are reported amongst patients with irritable bowel syndrome, inflammatory bowel disease, and nonintestinal disorders such as neuropsychiatric diseases and fibromyalgia. However, no reliable biomarkers currently exist to diagnose NCGS and hence confirmatory testing can only be performed using double-blind placebo controlled gluten-based challenges. Unfortunately, such tests are not available in routine clinical practice. Furthermore, recent novel studies have highlighted the role of other gluten-based components in contributing to the symptoms of self reported NCGS. These include fermentable oligo, di, mono-saccharides and polyols, amylase trypsin inhibitors, and wheat germ agglutinins. Therefore, NCGS is now seen as a spectrum encompassing several biological responses and terms such as 'noncoeliac wheat sensitivity' have been suggested as a wider label to define the condition. SUMMARY: Despite the rising use of a GFD further studies are required to clearly establish the extent and exclusivity of gluten in NCGS. PMID- 26808364 TI - Relationship between Functional Visual Acuity and Useful Field of View in Elderly Drivers. AB - PURPOSE: To investigate the relationship between the functional visual acuity (FVA) and useful field of view (UFOV) in elderly drivers and assess the usefulness of the FVA test to screen driving aptitude in elderly drivers. METHODS: This study included 45 elderly drivers (31 men, 14 women; mean age, 68.1 years) and 30 younger drivers (26 men, 4 women; mean age, 34.2 years) who drive regularly. All participants underwent measurement of the binocular corrected distant visual acuity (CDVA), binocular corrected distant FVA (CDFVA), and Visual Field with Inhibitory Tasks Elderly Version (VFIT-EV) to measure UFOV. The tear function and cognitive status also were evaluated. RESULTS: The CDVA, the CDFVA, cognitive status, and the correct response rate (CAR) of the VFIT-EV were significantly worse in the elderly group than in the control group (P = 0.000 for all parameters). The cognitive status was correlated significantly with the CDVA (r = -0.301, P = 0.009), CDFVA (r = -0.402, P = 0.000), and the CAR of the VFIT EV (r = 0.348, P = 0.002) in all subjects. The results of the tear function tests were not correlated with the CDVA, CDFVA, or VFIT-EV in any subjects. Stepwise regression analysis for all subjects in the elderly and control groups showed that the CDFVA predicted the CAR most significantly among the clinical factors evaluated. CONCLUSION: The FVA test is a promising method to screen the driving aptitude, including both visual and cognitive functions, in a short time. PMID- 26808365 TI - Prevalence of Celiac Disease in Children With Iron Deficiency Anemia in Van Lake Region of Turkey. AB - We aimed to determine the prevalence of celiac disease (CD) in children with iron deficiency anemia (IDA) and compare the hematological variables of these children with those with IDA, but not with CD. A total of 250 patients aged 1 to 16 years with IDA were included. Upper gastrointestinal system endoscopy was recommended to the patients who were serologically positive for CD. According to the endoscopic biopsy results of 12 patients who have positive screening tests (57.1%), Marsh grade II histopathologic findings were detected in 1 (4.8%) and Marsh grade III histopathologic findings were detected in 11 (52%). The hemoglobin, hematocrit, iron, and ferritin levels were significantly lower in patients with CD with IDA, compared with those with IDA, but not with CD. According to Marsh classification, the percentage of Marsh grade IIIc was found to be higher than the other Marsh grades. As the Marsh grading increased, hemoglobin, hematocrit, serum iron, and ferritin levels decreased and tissue transglutaminase Ig A levels increased. Our results show that CD should be kept in mind as the underlying etiologic factor in patients with IDA. PMID- 26808366 TI - Immune Thrombocytopenic Purpura Following Postexposure Rabies Prophylaxis. PMID- 26808367 TI - Acute Leukemia in Down Syndrome Children in Hong Kong: Retrospective Review. AB - BACKGROUND: Children with Down syndrome (DS) are at higher risk of developing acute leukemia. Treatment continues to evolve as we accumulate better understanding of the distinctive clinical and biological features of acute leukemia in DS patients. PROCEDURE: A retrospective review of the clinical features, treatment outcomes, and survival of DS children with acute leukemia in Hong Kong from 1993 to 2013 was conducted. Patients were identified from the registry of the Hong Kong Pediatric Hematology and Oncology study group. RESULTS: This cohort included a total of 29 patients with DS. Ten were diagnosed with acute lymphoblastic leukemia and 19 had acute myeloid leukemia (AML). The mean follow-up duration was 8.3 years (range, 0.6 mo to 18.1 y). The 5-year overall survival and event-free survival for DS-acute lymphoblastic leukemia and DS-AML were 65.6%, 54.9%, 89.5%, and 89.5%, respectively. CONCLUSIONS: The clinical characteristics and treatment outcomes of DS patients with acute leukemia in Hong Kong were comparable with results from other international study groups. Patients with DS-AML had a better prognosis. PMID- 26808368 TI - Allopurinol Use During Maintenance Therapy for Acute Lymphoblastic Leukemia Avoids Mercaptopurine-related Hepatotoxicity. AB - 6-Mercaptopurine (6-MP) is the mainstay of treatment for acute lymphoblastic leukemia and lymphoblastic lymphoma. It is metabolized into the pharmacologically active, 6-thioguanine nucleotide (6-TGN), and 6-methyl mercaptopurine nucleotides (6-MMPN), which is associated with hepatotoxicity that jeopardizes antileukemic therapy. Allopurinol alters the metabolism of 6-MP to increase 6-TGN levels and decreases 6-methyl mercaptopurine nucleotides levels. We report 2 cases in which combination therapy of allopurinol with 6-MP was used successfully to avoid hepatotoxicity while delivering adequate 6-TGN levels. We suggest that this combination therapy can be used safely to change the metabolite production in patients who develop excessive hepatotoxicity. PMID- 26808369 TI - Complete and Repeated Response of a Metastatic ALK-rearranged Inflammatory Myofibroblastic Tumor to Crizotinib in a Teenage Girl. AB - Inflammatory myofibroblastic tumors (IMT) are rare tumors in children and young adults, considered by the World Health Organization to be intermediate malignancies and rarely metastasizing, with the presence of an anaplastic lymphoma kinase rearrangement in about 50% of the cases. We report the case of a teenager who presented with a metastatic aggressive IMT that was life-threatening despite multiple treatments, and which responded repeatedly to anaplastic lymphoma kinase-targeted crizotinib therapy. Crizotinib induced drastic primary tumor regression, which was sufficient to allow surgical resection and to control distant disease. This case shows that crizotinib is a promising therapy in IMT, even in adolescents and young adults. PMID- 26808370 TI - Safety and Efficacy Outcomes of Home and Hospital Warfarin Management Within a Pediatric Anticoagulation Clinic. AB - The complexity of managing children with chronic disease has led to an increase in the use of long-term warfarin therapy. Time in therapeutic range (TTR) is the preferred method for determining efficacy and stability of warfarin management. This study aimed to determine the TTR achievement and incidence of adverse events among pediatric warfarin patients managed by an anticoagulation clinic over 12 months and to compare TTR achievement between patients self-testing (PST) at home and those monitored using routine methods. International normalized ratio (INR) results reported for 2012 for children currently having their warfarin therapy managed by a dedicated pediatric anticoagulation clinic were analyzed. Warfarin related adverse events were recorded. A total of 164 patients were included. In total, 93 children performed PST and 71 children tested their INR at a hospital or pathology service. TTR achievement for the cohort was 67.1% (95% confidence interval, 64.4-69.7). A total of 69.2% of INR tests conducted at home were within the TTR compared with 64.3% of INR tests conducted at a hospital or pathology service (P=0.07). One major bleeding event occurred and there was 1 thrombotic episode. PST demonstrated noninferior warfarin stability compared with routine methods. Routine outcome evaluation of pediatric anticoagulation management within single institutions is necessary to confirm the success of such programs. PMID- 26808371 TI - Long-term Health Outcomes in Survivors of Childhood Cancer Diagnosed Between 1990 and 2000 in a Large US Integrated Health Care System. AB - We evaluated the long-term health outcomes of childhood cancer survivors (CCS) using data from the Kaiser Permanente Southern California (KPSC) health plan, whose members have similar health care coverage. Five-year survivors of invasive cancer diagnosed at ages 0 to 18 years between 1990 and 2000 at KPSC were identified and followed to December 31, 2010. A group of KPSC members without history of cancer were 10:1 matched to each CCS for comparison. Health outcomes of interest included mortality, second cancer, and chronic comorbidities. Incidence rate ratio (IRR) was estimated using multivariable Poisson regression. Cumulative incidence of each health condition over time was calculated. A total of 652 CCS and 6520 noncancer subjects were included. Compared with the noncancer subjects, IRR was significantly elevated among CCS for mortality (IRR=14.1), second cancer (IRR=10.0), cerebrovascular disease (IRR=10.1), dyslipidemia (IRR=1.9), hearing/vision loss (IRR=5.1), heart disease (IRR=3.9), hypogonadism (IRR=4.2), renal failure (IRR=13.4), and thyroid disorder (IRR=6.4). Approximately 40% of CCS developed at least 1 chronic health condition within 15 years of cancer diagnosis. Cumulative incidence curves showed different risk trajectories of various comorbidities which may inform screening schedule. These data suggested that CCS treated in a more contemporary era continued to experience substantial disease burden in their adolescent and young adulthood. PMID- 26808372 TI - Immune Thrombocytopenic Purpura Following Postexposure Rabies Prophylaxis. PMID- 26808373 TI - A Severe Congenital Neutropenia Type 4 Case (G6PC3 Mutation) Presented With Large Platelets in the Peripheral Smear. AB - Severe congenital neutropenia type 4 is a disorder of the hematopoietic system associated with mutations in the glucose-6-phosphatase catabolic 3 (G6PC3) gene. This disorder is characterized by neutropenia, congenital heart defects, urogenital malformations, and prominent superficial veins. To our knowledge, although intermittent thrombocytopenia is observed in this mutation, the coexistence of large thrombocytes is rarely seen. Here we present a case of severe congenital neutropenia type 4 with G6PC3 mutation and large platelets in the peripheral smear. PMID- 26808375 TI - FRIZZLED7 Is Required for Tumor Initiation and Metastatic Growth of Melanoma Cells. AB - Metastases are thought to arise from cancer stem cells and their tumor initiating abilities are required for the establishment of metastases. Nevertheless, in metastatic melanoma, the nature of cancer stem cells is under debate and their contribution to metastasis formation remains unknown. Using an experimental metastasis model, we discovered that high levels of the WNT receptor, FZD7, correlated with enhanced metastatic potentials of melanoma cell lines. Knocking down of FZD7 in a panel of four melanoma cell lines led to a significant reduction in lung metastases in animal models, arguing that FZD7 plays a causal role during metastasis formation. Notably, limiting dilution analyses revealed that FZD7 is essential for the tumor initiation of melanoma cells and FZD7 knockdown impeded the early expansion of metastatic melanoma cells shortly after seeding, in accordance with the view that tumor initiating ability of cancer cells is required for metastasis formation. FZD7 activated JNK in melanoma cell lines in vitro and the expression of a dominant negative JNK suppressed metastasis formation in vivo, suggesting that FZD7 may promote metastatic growth of melanoma cells via activation of JNK. Taken together, our findings uncovered a signaling pathway that regulates the tumor initiation of melanoma cells and contributes to metastasis formation in melanoma. PMID- 26808376 TI - Soil Respiration in Semiarid Temperate Grasslands under Various Land Management. AB - Soil respiration, a major component of the global carbon cycle, is significantly influenced by land management practices. Grasslands are potentially a major sink for carbon, but can also be a source. Here, we investigated the potential effect of land management (grazing, clipping, and ungrazed enclosures) on soil respiration in the semiarid grassland of northern China. Our results showed the mean soil respiration was significantly higher under enclosures (2.17 MUmol.m( 2).s(-1)) and clipping (2.06 MUmol.m(-2).s(-1)) than under grazing (1.65 MUmol.m (2).s(-1)) over the three growing seasons. The high rates of soil respiration under enclosure and clipping were associated with the higher belowground net primary productivity (BNPP). Our analyses indicated that soil respiration was primarily related to BNPP under grazing, to soil water content under clipping. Using structural equation models, we found that soil water content, aboveground net primary productivity (ANPP) and BNPP regulated soil respiration, with soil water content as the predominant factor. Our findings highlight that management induced changes in abiotic (soil temperature and soil water content) and biotic (ANPP and BNPP) factors regulate soil respiration in the semiarid temperate grassland of northern China. PMID- 26808374 TI - Adaptive Landscape by Environment Interactions Dictate Evolutionary Dynamics in Models of Drug Resistance. AB - The adaptive landscape analogy has found practical use in recent years, as many have explored how their understanding can inform therapeutic strategies that subvert the evolution of drug resistance. A major barrier to applications of these concepts is a lack of detail concerning how the environment affects adaptive landscape topography, and consequently, the outcome of drug treatment. Here we combine empirical data, evolutionary theory, and computer simulations towards dissecting adaptive landscape by environment interactions for the evolution of drug resistance in two dimensions-drug concentration and drug type. We do so by studying the resistance mediated by Plasmodium falciparum dihydrofolate reductase (DHFR) to two related inhibitors-pyrimethamine and cycloguanil-across a breadth of drug concentrations. We first examine whether the adaptive landscapes for the two drugs are consistent with common definitions of cross-resistance. We then reconstruct all accessible pathways across the landscape, observing how their structure changes with drug environment. We offer a mechanism for non-linearity in the topography of accessible pathways by calculating of the interaction between mutation effects and drug environment, which reveals rampant patterns of epistasis. We then simulate evolution in several different drug environments to observe how these individual mutation effects (and patterns of epistasis) influence paths taken at evolutionary "forks in the road" that dictate adaptive dynamics in silico. In doing so, we reveal how classic metrics like the IC50 and minimal inhibitory concentration (MIC) are dubious proxies for understanding how evolution will occur across drug environments. We also consider how the findings reveal ambiguities in the cross resistance concept, as subtle differences in adaptive landscape topography between otherwise equivalent drugs can drive drastically different evolutionary outcomes. Summarizing, we discuss the results with regards to their basic contribution to the study of empirical adaptive landscapes, and in terms of how they inform new models for the evolution of drug resistance. PMID- 26808379 TI - A population-based study on the association between chronic periodontitis and sialolithiasis. AB - OBJECTIVES/HYPOTHESIS: Whereas the impression that poor oral hygiene is linked to the development of sialolithiasis may be widely accepted, very few studies provide evidence to support this. This study therefore aimed to evaluate the association between chronic periodontitis (CP) and the subsequent development of salivary gland stone based on a nationwide coverage database. STUDY DESIGN: A case-control study. METHODS: A total of 987 subjects with sialolithiasis were included as cases. In a ratio of five controls per case, 4,935 controls matched in terms of sex and age group were selected. Conditional logistic regression analysis was performed to determine the possible association of sialolithiasis with previously diagnosed CP. RESULTS: The prevalence of prior CP between cases and controls demonstrated that 1,831 (30.9%) out of the 5,922 sampled subjects had prior CP. By Chi-square test, there was a significant difference in the prevalence of prior CP between the cases and controls (36.8% vs. 29.7%, P < 0.001). By conditional logistic regression analysis, the odds ratio (OR) of prior CP for cases was 1.37 (95% confidence interval [CI], 1.19-1.56) compared to the controls after adjusting for geographic location and tobacco use. Further analyzing the relationship between sialolithiasis and prior CP according to sex, sialolithiasis was associated with prior CP regardless of sex. The adjusted OR of prior CP for the cases was 1.34 (95% CI, 1.10-1.64) and 1.41 (95% CI, 1.15-1.73) for males and females, respectively, when compared to controls. CONCLUSION: This study demonstrates an association between CP and sialolithiasis. LEVEL OF EVIDENCE: 3b. PMID- 26808377 TI - Corticotropin-Releasing Hormone Receptor 2 Gene Variants in Irritable Bowel Syndrome. AB - BACKGROUND: Corticotropin-releasing hormone (CRH) plays an important role in the pathophysiology of irritable bowel syndrome (IBS) and regulates the stress response through two CRH receptors (R1 and R2). Previously, we reported that a CRHR1 gene polymorphism (rs110402, rs242924, and rs7209436) and haplotypes were associated with IBS. However, the association between the CRHR2 gene and IBS was not investigated. We tested the hypothesis that genetic polymorphisms and haplotypes of CRHR2 are associated with IBS pathophysiology and negative emotion in IBS patients. METHODS: A total of 142 IBS patients and 142 healthy controls participated in this study. Seven single nucleotide polymorphisms (SNPs) of the CRHR2 gene (rs4722999, rs3779250, rs2240403, rs2267710, rs2190242, rs2284217, and rs2284220) were genotyped. Subjects' psychological states were evaluated using the Perceived-Stress Scale, the State-Trait Anxiety Inventory, and the Self Rating Depression Scale. RESULTS: We found that rs4722999 and rs3779250, located in intronic region, were associated with IBS in terms of genotype frequency (rs4722999: P = 0.037; rs3779250: P = 0.017) and that the distribution of the major allele was significantly different between patients and controls. There was a significant group effect (controls vs. IBS), and a CRHR2 genotype effect was observed for three psychological scores, but the interaction was not significant. We found a haplotype of four SNPs (rs4722999, rs3779250, rs2240403, and rs2267710) and two SNPs (rs2284217 and rs2284220) in strong linkage disequilibrium (D' > 0.90). We also found that haplotypes of the CRHR2 gene were significantly different between IBS patients and controls and that they were associated with negative emotion. CONCLUSION: Our findings support the hypothesis that genetic polymorphisms and haplotypes of CRHR2 are related to IBS. In addition, we found associations between CRHR2 genotypes and haplotypes and negative emotion in IBS patients and controls. Further studies on IBS and the CRH system are warranted. PMID- 26808380 TI - A model for the accurate computation of the lateral scattering of protons in water. AB - A pencil beam model for the calculation of the lateral scattering in water of protons for any therapeutic energy and depth is presented. It is based on the full Moliere theory, taking into account the energy loss and the effects of mixtures and compounds. Concerning the electromagnetic part, the model has no free parameters and is in very good agreement with the FLUKA Monte Carlo (MC) code. The effects of the nuclear interactions are parametrized with a two parameter tail function, adjusted on MC data calculated with FLUKA. The model, after the convolution with the beam and the detector response, is in agreement with recent proton data in water from HIT. The model gives results with the same accuracy of the MC codes based on Moliere theory, with a much shorter computing time. PMID- 26808381 TI - Stable Isotopes Reveal Long-Term Fidelity to Foraging Grounds in the Galapagos Sea Lion (Zalophus wollebaeki). AB - Most otariids have colony-specific foraging areas during the breeding season, when they behave as central place foragers. However, they may disperse over broad areas after the breeding season and individuals from different colonies may share foraging grounds at that time. Here, stable isotope ratios in the skull bone of adult Galapagos sea lions (Zalophus wollebaeki) were used to assess the long-term fidelity of both sexes to foraging grounds across the different regions of the Galapagos archipelago. Results indicated that the stable isotope ratios (delta(13)C and delta(15)N) of sea lion bone significantly differed among regions of the archipelago, without any significant difference between sexes and with a non significant interaction between sex and region. Moreover, standard ellipses, estimated by Bayesian inference and used as a measure of the isotopic resource use area at the population level, overlapped widely for the sea lions from the southern and central regions, whereas the overlap of the ellipses for sea lions from the central and western regions was small and non-existing for those from the western and southern regions. These results suggest that males and females from the same region within the archipelago use similar foraging grounds and have similar diets. Furthermore, they indicate that the exchange of adults between regions is limited, thus revealing a certain degree of foraging philopatry at a regional scale within the archipelago. The constraints imposed on males by an expanded reproductive season (~ 6 months), resulting from the weak reproductive synchrony among females, and those imposed on females by a very long lactation period (at least one year but up to three years), may explain the limited mobility of adult Galapagos sea lions of both sexes across the archipelago. PMID- 26808382 TI - Effects of Near Addition Lenses and Prisms on Accommodative Microfluctuations in Chinese Children. AB - PURPOSE: To investigate the effects of different near addition lenses and prisms on accommodative microfluctuations (AMFs) in Chinese early-onset myopic (EOM) and emmetropic (EMM) children. METHODS: Twenty-one EMM and 27 EOM children aged between 9 and 14years participated in the study. At near, 23 children were exophoric (exo, <0 Delta), and 25 were esophoric (eso, >=0 Delta). The AMFs and phoria through multiple addition lenses (-1.00, 0, +1.00, +2.00, and +3.00D on each eye) and prisms (base-in prism power: 3 Delta, 2 Delta, 1 Delta; and base out prism power: 1 Delta and 2 Delta on each eye) were measured at 25cm under binocular viewing conditions with a Grand Seiko WAM-5500 auto-refractor and a modified Thorington card. RESULTS: Higher AMFs were found in EOM than in EMM (EOM, 0.19+/-0.06D; EMM, 0.16+/-0.03D; p=0.035). Plus additions from +1.00 to +3.00D reduced the AMFs in both EMM and EOM, except +3.00D for EMM. In both refractive groups, -1.00D additions increased AMFs. Esophores showed greater AMFs compared with exophores (esophores, 0.20+/-0.01D; exophores, 0.16+/-0.01D; p=0.012). Prisms increased the AMFs in EMM and did not alter the AMFs in EOM. CONCLUSIONS: Microfluctuations of accommodation decreased with plus addition lenses and increased with negative addition lenses. Plus addition lenses of +2.00 to +3.00D for EOM and +2.00D for EMM decreased AMFs the least at a 25-cm working distance. Esophores had higher AMFs than exophores, indicating that phoria status influences AMFs. PMID- 26808383 TI - Lack of Agreement among Electrical Impedance and Freezing-Point Osmometers. AB - PURPOSE: To assess the interchangeability of tear osmolarity measurements between electrical impedance and freezing-point depression osmometers and to analyze inter-eye tear osmolarity variability measured with these osmometers in healthy subjects. METHODS: Tear osmolarity was measured using the TearLab osmometer (OcuSense Inc., San Diego, CA) and the Fiske 210 microsample osmometer (Advanced Instruments Inc., Norwood, MA). We randomly selected one eye in 50 subjects (29 women, 21 men; mean age, 33.16 +/- 6.11 years) to analyze whether osmolarity measurements by these osmometers were interchangeable. Both eyes of 25 patients (15 women, 10 men; mean age, 34.32 +/- 6.37 years) were included to analyze inter eye osmolarity variability. RESULTS: The mean tear osmolarity values measured with the TearLab osmometer were higher (305.22 +/- 16.06 mOsm/L) than those with the Fiske 210 osmometer (293.40 +/- 12.22 mOsm/L), with the intraclass correlation coefficient being 0.23 (p = 0.051). A Bland-Altman plot showed that the systems were not interchangeable because there was a systematic difference, with the limits of agreement being -17.93 to 41.57 mOsm/L. There were no statistically significant differences (p = 0.5006 and p = 0.6533, respectively) between an individual's eyes measured with either osmometer. CONCLUSIONS: Because the TearLab tear osmolarity measurements were higher than those of the Fiske 210 measurements and the limits of agreement were too wide, the two osmolarity values cannot be used interchangeably. In healthy subjects, there is no difference in tear osmolarity between right and left eyes of the same individual measured with both instruments. PMID- 26808384 TI - Short-Term Visual Performance of Novel Extended Depth-of-Focus Contact Lenses. AB - PURPOSE: To compare the objective and subjective visual performance of a novel contact lens which extends depth of focus by deliberate manipulation of higher order spherical aberrations and a commercially available zonal-refractive multifocal lens. METHODS: A prospective, cross-over, randomized, single-masked, short-term clinical trial comprising 41 presbyopes (age 45 to 70 years) wearing novel Extended Depth of Focus lenses (EDOF) and ACUVUE OAYS for Presbyopia (AOP). Each design was assessed on different days with a minimum overnight wash-out. Objective measures comprised high-contrast visual acuity (HCVA, logMAR) at 6 m, 70 cm, 50 cm, and 40 cm; low-contrast visual acuity (LCVA, logMAR) and contrast sensitivity (log units) at 6 m; and stereopsis (seconds of arc) at 40 cm. HCVA at 70 cm, 50 cm, and 40 cm were measured as "comfortable acuity" rather than conventional resolution acuity. Subjective performance was assessed on a 1-10 numeric rating scale for clarity of vision and ghosting at distance, intermediate and near, overall vision satisfaction, ocular comfort, and lens purchase. Statistical analysis included repeated measures ANOVA and paired t tests. RESULTS: HCVA, clarity of vision, and ghosting with EDOF were significantly better than AOP (p < 0.01); however, differences were dependent on testing distances and add groups. Post hoc analysis showed EDOF was significantly better than AOP for HCVA at 70 cm (0.11 +/- 0.11 vs. 0.21 +/- 0.16, p < 0.001), 50 cm (0.26 +/- 0.17 vs. 0.36 +/- 0.18, p = 0.003), 40 cm (0.42 +/- 0.17 vs. 0.52 +/- 0.21, p = 0.001), and LCVA at 6 m (0.22 +/- 0.08 vs. 0.27 +/- 0.12, p = 0.024). EDOF was significantly better than AOP for clarity of vision at distance (7.7 +/- 1.6 vs. 6.8 +/- 2.3, p = 0.029), intermediate (8.8 +/- 1.4 vs. 7.0 +/- 2.2, p < 0.001), and near (7.4 +/- 2.4 vs. 5.2 +/- 2.7, p < 0.001), ghosting at distance (9.1 +/- 1.2 vs. 8.1 +/- 2.5, p = 0.005), and overall vision satisfaction (7.6 +/ 1.6 vs. 6.0 +/- 2.6, p < 0.001). More participants chose to purchase EDOF compared to AOP (61 vs. 39%) and significantly more chose to only-purchase EDOF compared to only-purchase AOP (27 vs. 5%, p = 0.022). CONCLUSIONS: When compared with AOP, EDOF lenses provide better intermediate and near vision performance in presbyopic participants without compromising distance vision. PMID- 26808385 TI - ssDNA Aptamer Specifically Targets and Selectively Delivers Cytotoxic Drug Doxorubicin to HepG2 Cells. AB - Hepatocellular carcinoma (HCC) is the third leading cause of death due to cancer worldwide with over 500,000 people affected annually. Although chemotherapy has been widely used to treat patients with HCC, alternate modalities to specifically deliver therapeutic cargos to cancer cells have been sought in recent years due to the severe side effects of chemotherapy. In this respect, aptamer-based tumor targeted drug delivery has emerged as a promising approach to increase the efficacy of chemotherapy and reduce or eliminate drug toxicity. In this study, we developed a new HepG2-specific aptamer (HCA#3) by a procedure known as systematic evolution of ligands by exponential enrichment (SELEX) and exploited its role as a targeting ligand to deliver doxorubicin (Dox) to HepG2 cells in vitro. The selected 76-base nucleotide aptamer preferentially bound to HepG2 hepatocellular carcinoma cells but not to control cells. The aptamer HCA#3 was modified with paired CG repeats at the 5'-end to carry and deliver a high payload of intercalated Dox molecules at the CG sites. Four Dox molecules (mol/mol) were fully intercalated in each conjugate aptamer-Dox (ApDC) molecule. Biostability analysis showed that the ApDC molecules are stable in serum. Functional analysis showed that ApDC specifically targeted and released Dox within HepG2 cells but not in control cells, and treatment with HCA#3 ApDC induced HepG2 cell apoptosis but had minimal effect on control cells. Our study demonstrated that HCA#3 ApDC is a promising aptamer-targeted therapeutic that can specifically deliver and release a high doxorubicin payload in HCC cells. PMID- 26808386 TI - The further characterization of the peptide specifically binding to gastric cancer. AB - Targeting peptide has been considered to be useful as a small molecule probe leading to multifunctional properties for both imaging detection and targeting therapy. Thus, the identification of novel targets is urgently needed to develop innovative agents to effectively control gastric cancer metastasis and progression. Previously, we reported a novel 12-mer peptide, GP-5 (IHKDKNAPSLVP), binding to gastric carcinoma (GC) cells specifically and sensitively, and it was screened by using a phage displayed peptide library and primarily analyzed. In this study, it was further identified via fluorescence microscopy, flow cytometry, tissue chip and other methods. Our results indicated that the peptide GP-5 presents a particularly high affinity and specificity to GC cells and tissues, whereas only background detection occurred with other control cancer cells, cancer tissues or normal tissues. Taken together, all results support that the peptide GP-5 is a potential candidate to be developed as a useful molecule fragment for the imaging detection and targeting therapy of GC. PMID- 26808387 TI - Soret and Dufour Effects on MHD Peristaltic Flow of Jeffrey Fluid in a Rotating System with Porous Medium. AB - The objective of present paper is to examine the peristaltic flow of magnetohydrodynamic (MHD) Jeffrey fluid saturating porous space in a channel through rotating frame. Unlike the previous attempts, the flow formulation is based upon modified Darcy's law porous medium effect in Jeffrey fluid situation. In addition the impacts due to Soret and Dufour effects in the radiative peristaltic flow are accounted. Rosseland's approximation has been utilized for the thermal radiative heat flux. Lubrication approach is implemented for the simplification. Resulting problems are solved for the stream function, temperature and concentration. Graphical results are prepared and analyzed for different parameters of interest entering into the problems. PMID- 26808388 TI - Angiotensin II Induced Cardiac Dysfunction on a Chip. AB - In vitro disease models offer the ability to study specific systemic features in isolation to better understand underlying mechanisms that lead to dysfunction. Here, we present a cardiac dysfunction model using angiotensin II (ANG II) to elicit pathological responses in a heart-on-a-chip platform that recapitulates native laminar cardiac tissue structure. Our platform, composed of arrays of muscular thin films (MTF), allows for functional comparisons of healthy and diseased tissues by tracking film deflections resulting from contracting tissues. To test our model, we measured gene expression profiles, morphological remodeling, calcium transients, and contractile stress generation in response to ANG II exposure and compared against previous experimental and clinical results. We found that ANG II induced pathological gene expression profiles including over expression of natriuretic peptide B, Rho GTPase 1, and T-type calcium channels. ANG II exposure also increased proarrhythmic early after depolarization events and significantly reduced peak systolic stresses. Although ANG II has been shown to induce structural remodeling, we control tissue architecture via microcontact printing, and show pathological genetic profiles and functional impairment precede significant morphological changes. We assert that our in vitro model is a useful tool for evaluating tissue health and can serve as a platform for studying disease mechanisms and identifying novel therapeutics. PMID- 26808389 TI - Can Immune Response Mechanisms Explain the Fecal Shedding Patterns of Cattle Infected with Mycobacterium avium Subspecies paratuberculosis? AB - Johne's disease (JD) is a chronic disease in ruminants and is caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP). At late stages of the disease, MAP bacilli are shed via feces excretion and in turn create the potential for oral-fecal transmission. The role of the host immune response in MAP bacteria shedding patterns at different stages of JD is still unclear. We employed mathematical modeling to predict if the variation in MAP shedding could be correlated to the immune response in infected animals. We used a novel inverse modeling approach that assumed biological interactions among the antigen-specific lymphocyte proliferation response (cell-mediated response), antibody/humoral immune responses, and MAP bacteria. The modeling framework was used to predict and test possible biological interactions between the measured variables and returns only the essential interactions that are relevant in explaining the observed cattle MAP experimental infection data. Through confronting the models with data, we predicted observed effects (enhancement or suppression) and extents of interactions among the three variables. This analysis enabled classification of the infected cattle into three different groups that correspond to the unique predicted immune responses that are essential to explain the data from cattle within these groups. Our analysis highlights the strong and weak points of the modeling approach, as well as the key immune mechanisms predicted to be expressed in all animals and those that were different between animals, hence giving insight into how animals exhibit different disease dynamics and bacteria shedding patterns. PMID- 26808390 TI - Rural-Urban Differences in Satisfaction with Medicare Part D: Implications for Policy. AB - Rural residents are more likely to be enrolled in traditional fee-for-service Part D Medicare prescription drug plans, and they face particular challenges in accessing pharmaceutical care. This study examines rural/urban differences in satisfaction with Medicare Part D coverage. Using data from the 2012 Medicare Current Beneficiary Survey (N = 3,107 beneficiaries aged 65 and older), we find that rural residents have significantly lower satisfaction with Part D coverage but that regional variation in satisfaction is largely explained by differences in health services use and type of Part D plan (stand-alone versus Medicare Advantage). We conclude by suggesting a multifaceted approach to improving satisfaction with Part D for rural residents. PMID- 26808391 TI - A Dual Non-ATP Analogue Inhibitor of Aurora Kinases A and B, Derived from Resorcinol with a Mixed Mode of Inhibition. AB - Aurora kinases are the most commonly targeted mitotic kinases in the intervention of cancer progression. Here, we report a resorcinol derivative, 5-methyl-4-(2 thiazolylazo) resorcinol (PTK66), a dual inhibitor of Aurora A and Aurora B kinases. PTK66 is a surface binding non-ATP analogue inhibitor that shows a mixed pattern of inhibition against both of Aurora A and B kinases. The in vitro IC50 is approximately 47 and 40 MUm for Aurora A and Aurora B kinases, respectively. In cellular systems, PTK66 exhibits a substantially low cytotoxicity at micromolar concentrations but it can induce aneuploidy under similar dosages as a consequence of Aurora kinase inhibition. This result was corroborated by a drop in the histone H3 (S10) phosphorylation level detected via Western blot analysis using three different cell types. Altogether, our findings indicate that the ligand containing resorcinol backbone is one of the novel scaffolds targeting the Aurora family of kinases, which could be a target for antineoplastic drug development. PMID- 26808392 TI - Contrast-enhanced susceptibility weighted imaging with ultrasmall superparamagnetic iron oxide improves the detection of tumor vascularity in a hepatocellular carcinoma nude mouse model. AB - PURPOSE: To evaluate the effectiveness of contrast-enhanced susceptibility weighted imaging with ultrasmall superparamagnetic iron oxide (USPIO-enhanced SWI) in the assessment of intratumoral vascularity in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Orthotopic xenograft HCC nude mouse models were established first and magnetic resonance imaging (MRI) examinations were performed on a 1.5T MR scanner 28 days later. Three groups of mice, 10 in each, were imaged using unenhanced and USPIO-enhanced SWI at doses of 4, 8, and 12 mg Fe/kg. Intratumoral susceptibility signal intensity (ITSS) was scored. ITSS-to tumor contrast-to-noise ratio (ITSST-CNR) was measured. These measurements were compared between unenhanced and USPIO-enhanced SWI at each dose and differences in the measurements between different dose groups were estimated. Correlation between ITSS and tumor microvessel density (MVD) was analyzed. RESULTS: Compared with unenhanced SWI, significantly higher ITSS was identified on USPIO-enhanced SWI at doses of 8 mg Fe/kg (Z = -2.000, P = 0.046) and 12 mg Fe/kg (Z = -2.333, P = 0.020). Significantly higher ITSST-CNR was found on USPIO-enhanced SWI than that on unenhanced SWI (P < 0.05). Significantly higher ITSST-CNR at a dose of 8 mg Fe/kg was observed than that at 4 mg Fe/kg (Z = -3.326, P = 0.001). Positive correlation between ITSS on USPIO-enhanced SWI at a dose of 8 mg Fe/kg and tumor MVD was demonstrated (r = 0.817, P = 0.004). CONCLUSION: USPIO-enhanced SWI at a dose of 8 mg Fe/kg greatly improves the detection of intratumoral vascularity in a xenograft HCC model. J. Magn. Reson. Imaging 2016;44:288-295. PMID- 26808393 TI - Screening primary sclerosing cholangitis and biliary dysplasia with endoscopic retrograde cholangiography and brush cytology: risk factors for biliary neoplasia. AB - BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is associated with increased risk of biliary dysplasia and cholangiocarcinoma (CCA). The aim of this study was to evaluate the role of early endoscopic retrograde cholangiography (ERC) with systematic brush cytology to identify risk factors associated with biliary neoplasia. PATIENTS AND METHODS: Patients who were referred for their first ERC for suspicion of PSC between January 2006 and October 2011 were included in the study. Brush cytology specimens were scored as benign, suspicious, or malignant. End points were CCA, biliary dysplasia, benign histology, or benign disease course for >= 2 years. RESULTS: PSC was diagnosed in 261 patients (125 men, 136 women), most of whom were asymptomatic (n = 211). Cholangiographic changes were mild in 57.1 %. Men presented with advanced disease more often than women. Brush cytology was benign in 243, suspicious in 16, and malignant in 2 patients. Follow-up completed in 249 patients indicated a benign disease course in 232 patients. Seven patients were diagnosed with CCA and eight had biliary dysplasia in the explanted liver. Thus, 15 patients had biliary neoplasia, and suspicious or malignant brush cytology had been detected in 8 of them at initial brushing. Advanced extrahepatic cholangiographic changes with elevated aminotransferases at diagnosis seemed to be associated with increased risk of biliary neoplasia. CONCLUSIONS: Even in mostly asymptomatic patients with PSC, 42.9 % had advanced disease and 6.9 % presented with suspicious or malignant brush cytology at first ERC. Advanced extrahepatic ERC changes with elevated aminotransferases at diagnosis might be risk factors for biliary neoplasia. PMID- 26808394 TI - Temporal trends and variability of colonoscopy performance in a gastroenterology practice. AB - BACKGROUND AND STUDY AIM: Quality measures for colonoscopy are operator dependent and vary. It is unclear whether quality measures change over time. In this study, time-dependent variation in colonoscopy performance was examined in a gastroenterology practice. PATIENTS AND METHODS: Colonoscopy and histopathology records that were collected at three hospitals (one university and two non university hospitals) over three time periods (2007, 2010, and 2013) were reviewed. Data from colonoscopists performing at least 100 procedures per year were analyzed. Inter-colonoscopist variation in performance (i. e. adjusted cecal intubation rate [aCIR], adenoma detection rate [ADR], advanced ADR, mean adenomas per procedure [MAP], proximal ADR, nonpolypoid ADR, and serrated polyp detection rate) were examined using coefficients of variation. Logistic regression analyses were also performed, adjusting for covariates. RESULTS: A total of 23 colonoscopists performing 6400 procedures were included. Overall, the mean aCIR, ADR, MAP, and proximal ADR improved significantly over time, from 91.9 %, 22.5 %, 0.37, and 10.2 % in 2007 to 95.3 %, 25.8 %, 0.45, and 13.4 %, respectively, in 2013 (P < 0.05). The inter-colonoscopist variation in ADR decreased from 37 % in 2007 to 15 % in 2013 (P < 0.05). In the non-university hospitals, mean values for quality measures increased significantly over time, whereas they remained stable in the university hospital. CONCLUSIONS: Variability in performance among colonoscopists decreased significantly within the gastroenterology clinical practice. Core quality measures improved over time, mainly through improvement of the lower performers. Measurement of inter-colonoscopist variation in performance helps to identify factors that stimulate or hinder performance, and forms the basis for interventions. TRIAL REGISTRATION: http://www.trialregister.nl. PMID- 26808395 TI - Clinicopathological, endoscopic, and molecular characteristics of the "skirt" - a new entity of lesions at the margin of laterally spreading tumors. AB - BACKGROUND AND STUDY AIM: A slightly elevated flat lesion with wide pits has occasionally been observed at the margin of laterally spreading tumors (LSTs) and is known as a "skirt." The aim of this study was to evaluate the clinicopathological, endoscopic, and genetic characteristics of a skirt. PATIENTS AND METHODS: Consecutive LSTs were examined to evaluate the pathological, endoscopic, and genetic characteristics. Pathological characteristics, including the dimension of the cryptic opening (DCO), width of the individual gland (WIG), DCO to WIG ratio, and microvessel diameter were elucidated and compared with those of hyperplastic polyps, low grade dysplasia (LGD), and normal mucosa. The endoscopic findings of pit and microvascular patterns were assessed. Gene mutation analyses were performed for the KRAS, BRAF, NRAS, and PIK3CA genes. RESULTS: A skirt was identified in 35 of 1023 LSTs, and 80 % of lesions with a skirt had a component of either intramucosal or submucosal adenocarcinoma. The DCO, WIG, and DCO to WIG ratio of the skirt were significantly larger than those of other lesions. The microvessel diameters in skirts were significantly smaller than those in LGDs. Regarding the endoscopic findings, 30 skirts showed pits with a coral reef-like appearance, and all skirt regions were found to have a type I capillary pattern. KRAS mutation at codon 146 was found in the nodular part in one of five LSTs with a skirt. CONCLUSION: The skirt is a newly identified lesion distinct from hyperplastic polyps and LGDs, suggesting the presence of a novel pathway for rectal carcinogenesis from LSTs with a skirt. PMID- 26808396 TI - Monitoring colonoscopy withdrawal time significantly improves the adenoma detection rate and the performance of endoscopists. AB - BACKGROUND AND STUDY AIMS: The recommended minimum withdrawal time for screening colonoscopy is 6 minutes. Adenoma detection rates (ADRs) increase with longer withdrawal times. We aimed to compare withdrawal times and ADRs of endoscopists unaware of being monitored vs. aware. PATIENTS AND METHODS: Seven experienced gastroenterologists prospectively performed 558 screening colonoscopies during a 9-month period in a Swiss University hospital. Colonoscopy withdrawal times were first measured without the gastroenterologists' knowledge of being monitored (n = 355 colonoscopies) and then with their knowledge (n = 203 colonoscopies). RESULTS: The median withdrawal time when gastroenterologists were unaware of being monitored was 4.5 minutes (interquartile range [IQR] 4 - 5.5 minutes) without intervention and 6 minutes (IQR 4 - 9 minutes) with intervention, increasing significantly to 7.3 minutes (IQR 6.5 - 9 minutes) and 8 minutes (IQR 7 - 11 minutes), respectively, when they were aware of being monitored (P < 0.001 both for colonoscopies with and without intervention). The ADR increased from 21.4 % when the gastroenterologists were unaware of being monitored to 36.0 % when they were aware (P < 0.001). In the multivariate regression model, the endoscopists knowing they were being monitored was the strongest factor associated with ADR (odds ratio 4.417; 95 % confidence interval [CI] 2.241 - 8.705; P < 0.001). CONCLUSIONS: Colonoscopy withdrawal time in unmonitored gastroenterologists is shorter than recommended and increases with awareness of monitoring. ADR significantly increases when gastroenterologists are aware of being monitored. Implementation of systematic monitoring, and analysis of withdrawal time and ADR for each endoscopist may help to increase the ADR. PMID- 26808397 TI - Transactional sex and sexual harassment between professors and students at an urban university in Benin. AB - This paper adds to discussion of transactional sex relationships in Africa by examining the distinction between transactional sex and sexual harassment in the context of professor-student relationships and their inherent power dynamics. By exploring the ways in which female university students in urban Benin toe the line between empowered agent and victim, I show how the power differential between professor and student obstructs the professor's ability to objectively determine consent, and examine why, in spite of this differential, male professors are frequently perceived as the victims of these relationships. Ethnographic data were gathered through participant observation on a public university campus in Benin and in-depth interviews and focus groups with 34 students and 5 professors from that university. Findings suggest that the problem of sexual harassment on campus will be difficult to address so long as transactional sex relationships between professors and students are permitted to continue. PMID- 26808398 TI - "Real-Time" Monitoring of Under-Five Mortality: A Vision Tempered by Reality. PMID- 26808399 TI - Source apportionment and risk assessment of PM1 bound trace metals collected during foggy and non-foggy episodes at a representative site in the Indo-Gangetic plain. AB - The concentration, spatial distribution and source of 13-PM1 bound trace metals (Fe, Cu, Mn, Cr, Zn, Cd, Ni, K, Mg, Na, Ca, Pb and V) and adverse health effects of 5-PM1 bound trace metals (Mn, Zn, Ni, Cr and Cd) collected during foggy and non-foggy episodes are presented. Twenty-four samples from each period (foggy and non-foggy episodes) were collected from Kanpur, a typical densely populated city and the most polluted representative site in the Indo-Gangetic plain of India, and were analyzed for carcinogenic (Ni, Cr and Cd) and non-carcinogenic metals (Mn and Zn). The average mass concentration of PM1 during foggy and non-foggy episodes was found to be 160.16+/-37.70 and 132.87+/-27.97MUg/m(3). Source identification via principle component analysis suggested that vehicular emission and anthropogenic, industrial and crustal dust were the dominant sources in this region. During both episodes the decreasing order of hazard quotient (Hq) for adult and children was as Mn>Cr>Cd>Ni>Zn. In a non-foggy episode the hazardous index (Hi) values of these 5 trace metals were found to be ~3.5 times higher than a foggy episode's exposed population, respectively. In a foggy episode, due to the exposure to total carcinogenic trace metals (Ni, Cr and Cd) present in the ambient air, 95% probability total incremental lifetime cancer risks (TIlcR) were ~687 cancer cases and ~402 cancer cases per million in the adult population and children population respectively. These cancer cases were ~1.6 times higher than a non-foggy episode's exposed population. PMID- 26808400 TI - Enhancing zero valent iron based natural organic matter removal by mixing with dispersed carbon cathodes. AB - Former studies have shown that adding granular activated carbon (GAC) cathodes could enhance the overall performance of the zero valent iron (ZVI) process for organics removal. The present study evaluates for the first time the performance of such an enhanced ZVI process to remove natural organic matter (NOM), an important water quality parameter in drinking water. Lab-scale batch tests were conducted with surface reservoir feed water from a drinking water plant. In the GAC enhanced ZVI process dissolved organic carbon (DOC) and UV254 were reduced by 61+/-3% and 70+/-2%, respectively, during 24h treatment corresponding to 1.8min empty bed contact time. The process was superior to ZVI alone, particularly during the earlier stages of the process due to the synergistically increased iron dissolution rate. Besides GAC, graphite and anthracite also prove to be suitable and potentially more cost-effective options as cathode materials for the enhanced ZVI process, whereby electrically conductive graphite clearly outperformed anthracite. The dominant mechanisms in terms of NOM removal from surface water were found to be coagulation following iron dissolution and adsorption in the case of employing GAC. Oxidation was also occurring to a lesser degree, converting some non-biodegradable into biodegradable DOC. PMID- 26808401 TI - Molybdenum and zinc stable isotope variation in mining waste rock drainage and waste rock at the Antamina mine, Peru. AB - The stable isotope composition of molybdenum (Mo) and zinc (Zn) in mine wastes at the Antamina Copper-Zn-Mo mine, Peru, was characterized to investigate whether isotopic variation of these elements indicated metal attenuation processes in mine drainage. Waste rock and ore minerals were analyzed to identify the isotopic composition of Mo and Zn sources, namely molybdenites (MoS2) and sphalerites (ZnS). Molybdenum and Zn stable isotope ratios are reported relative to the NIST SRM-3134 and PCIGR-1 Zn standards, respectively. delta(98)Mo among molybdenites ranged from -0.6 to +0.60/00 (n=9) while sphalerites showed no delta(66)Zn variations (0.11+/-0.010/00, 2 SD, n=5). Mine drainage samples from field waste rock weathering experiments were also analyzed to examine the extent of isotopic variability in the dissolved phase. Variations spanned 2.20/00 in delta(98)Mo ( 0.1 to +2.10/00) and 0.70/00 in delta(66)Zn (-0.4 to +0.30/00) in mine drainage over a wide pH range (pH2.2-8.6). Lighter delta(66)Zn signatures were observed in alkaline pH conditions, which was consistent with Zn adsorption and/or hydrozincite (Zn5(OH)6(CO3)2) formation. However, in acidic mine drainage Zn isotopic compositions reflected the value of sphalerites. In addition, molybdenum isotope compositions in mine drainage were shifted towards heavier values (0.89+/ 1.250/00, 2 SD, n=16), with some overlap, in comparison to molybdenites and waste rock (0.13+/-0.820/00, 2 SD, n=9). The cause of heavy Mo isotopic signatures in mine drainage was more difficult to resolve due to isotopic heterogeneity among ore minerals and a variety of possible overlapping processes including dissolution, adsorption and secondary mineral precipitation. This study shows that variation in metal isotope ratios are promising indicators of metal attenuation. Future characterization of isotopic fractionation associated to key environmental reactions will improve the power of Mo and Zn isotope ratios to track the fate of these elements in mine drainage. PMID- 26808402 TI - Dioxins and dl-PCBs in gull eggs from Spanish Natural Parks (2010-2013). AB - The aim of this study was to evaluate the presence and distribution of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and biphenyls (PCBs), concretely those so-called as dioxin-like PCBs, in yellow-legged gull eggs (Larus michahellis) collected from five Natural Parks (some of them National Parks) in Spain during the period 2010-2013. PCDD/Fs and dl-PCBs were detected in all the samples. Due to the proximity to important urban and industrial areas higher concentrations were determined in colonies located in the Northern Mediterranean coast than those found in the Southern Mediterranean or Atlantic colonies where a softer anthropogenic impact occurs. Mean ?PCDD/F concentrations ranged from 49 to 223pg/g lipid weight (lw) and ?dl-PCB concentrations varied from 146 to 911ng/g lw. In the Natural Park of the Ebro Delta (Northern Mediterranean coast) two gull species share habitat: yellow-legged and Audouin gull (Larus audouinii). Eggs from both species were collected and PCDD/F and dl-PCB levels compared. The species that feeds exclusively on pelagic fish (L. audouinii) had significantly higher PCDD/F and dl-PCB levels than the scavenger L. michahellis, pointing out the diet-dependent differences in the accumulation of persistent organic pollutants between similar cohabitant breeding species. Finally, mean TEQ values were in general below those considered as critical for toxicological effects in birds. PMID- 26808403 TI - Chemical composition of PM2.5 from two tunnels with different vehicular fleet characteristics. AB - The chemical compositions of PM2.5 including OC, EC, water soluble ions, elements, and organic components such as polycyclic aromatic hydrocarbons (PAHs), hopanes, and steranes, emitted in Wuzushan (WZS) and Kuixinglou (KXL) tunnels were determined. WZS tunnel is a major route for diesel vehicles traveling, while KXL tunnel has limited to diesel vehicles. The results showed that the proportions of the different constituents of PM2.5 in the Wuzushan (WZS) tunnel were OC (27.7%), EC (32.1%), elements (13.9%), and water soluble ions (9.2%). Whereas the chemical profile of PM2.5 in the Kuixinglou (KXL) tunnel was OC (17.7%), EC (10.4%), elements (8.90%), and water soluble ions (8.87%). The emission factors (EFs) of PM2.5 and proportions of SO4(2-) and Pb were decreased by vehicle emission standards and fuel quality policy in China, and the higher molecular weight PAHs (4+5+6 rings) were more abundant than the lower molecular weight PAHs (2+3 rings) in the two tunnels. The proportions of 17A(H)-21B(H)-30 Norhopane and 17A(H)-21B(H)-Hopane in the hopane and sterane were not dependent on the vehicles types. In addition, specific composition profiles for PM2.5 from gasoline-fueled vehicles (GV) and diesel-fueled vehicles (DV) emissions were drafted, which indicated that OC (0.974mg.veh(-1).km(-1)) was the most abundant component in PM2.5, followed by Fe, Cl(-), and Mg for GV. The relative proportions of the different constituents in the PM2.5 for DV were EC (35.9%), OC (27.2%), elements (12.8%), and water soluble ions (11.7%). Both the PM2.5 EFs and EC proportions in DV were higher than those in GV, and the HMW PAHs were the dominant PAHs for both GV and DV. The PM2.5 emissions from the vehicles in Yantai were 581+/-513tons to 1353+/-1197tons for GV, and 19,627+/-2477tons to 23,042+/ 2887tons for DV, respectively. PMID- 26808404 TI - Characterisation of waste derived biochar added biocomposites: chemical and thermal modifications. AB - A step towards sustainability was taken by incorporating waste based pyrolysed biochar in wood and polypropylene biocomposites. The effect of biochar particles on the chemistry and thermal makeup of the composites was determined by characterising them through an array of characterisation techniques such as 3D optical profiling, X-ray diffraction, transmission electron microscopy, electron spin/nuclear magnetic resonance spectroscopy, and differential scanning calorimetry. It was observed that addition of biochar increased the presence of free radicals in the composite while also improving its thermal conductivity. Biochar particles did not interfere with the melting behaviour of polymer in the thermal regime. However, wood and biochar acted as nucleation agents consequently increasing the crystallisation temperature. The crystal structure of polypropylene was not disrupted by biochar inclusion in composite. Transmission electron microscopy images illustrated the aggregated nature of the biochar particles at higher loading levels. Nuclear magnetic resonance studies revealed the aromatic nature of biochar and the broadening of peak intensities of composites with increasing biochar levels due to its amorphous nature and presence of free radicals. Thus, this insight into the chemical and thermal modification of biochar added composites would allow effective engineering to optimise their properties while simultaneously utilising wastes. PMID- 26808405 TI - Accounting for land use in life cycle assessment: The value of NPP as a proxy indicator to assess land use impacts on ecosystems. AB - Terrestrial land and its resources are finite, though, for economic and socio cultural needs of humans, these natural resources are further exploited. It highlights the need to quantify the impact humans possibly have on the environment due to occupation and transformation of land. As a starting point of this paper (1(st) objective), the land use activities, which may be mainly socio culturally or economically oriented, are identified in addition to the natural land-based processes and stocks and funds that can be altered due to land use. To quantify the possible impact anthropogenic land use can have on the natural environment, linked to a certain product or service, life cycle assessment (LCA) is a tool commonly used. During the last decades, many indicators are developed within the LCA framework in an attempt to evaluate certain environmental impacts of land use. A second objective of this study is to briefly review these indicators and to categorize them according to whether they assess a change in the asset of natural resources for production and consumption or a disturbance of certain ecosystem processes, i.e. ecosystem health. Based on these findings, two enhanced proxy indicators are proposed (3(rd) objective). Both indicators use net primary production (NPP) loss (potential NPP in the absence of humans minus remaining NPP after land use) as a relevant proxy to primarily assess the impact of land use on ecosystem health. As there are two approaches to account for the natural and productive value of the NPP remaining after land use, namely the Human Appropriation of NPP (HANPP) and hemeroby (or naturalness) concepts, two indicators are introduced and the advantages and limitations compared to state-of the-art NPP-based land use indicators are discussed. Exergy-based spatially differentiated characterization factors (CFs) are calculated for several types of land use (e.g., pasture land, urban land). PMID- 26808406 TI - D-Alanylation in the Assembly of Ansatrienin Side Chain Is Catalyzed by a Modular NRPS. AB - Ansatrienins are a group of ansamycins with an N-cyclohexanoyl d-alanyl side chain. Though ansatrienins have been identified for decades, the mechanism for the addition of this unique side chain was not established. Here, we report the biochemical characterization of a tridomain nonribosomal peptide synthetase (NRPS), AstC, and an N-acyltransferase, AstF1, encoded in the biosynthetic pathway of ansatrienins. We demonstrate that AstC can efficiently catalyze the transfer of d-alanine to the C-11 hydroxyl group of ansatrienins, and AstF1 is able to attach the cyclohexanoyl group to the amino group of d-alanine. Remarkably, AstC presents the first example that a modular NRPS can catalyze intermolecular d-alanylation of the hydroxyl group to form an ester bond, though alanyl natural products have been known for decades. In addition, both AstC and AstF1 have broad substrate specificity toward acyl donors, which can be utilized to create novel ansatrienins. PMID- 26808407 TI - The Physician-Patient Working Alliance in Hemodialysis Treatment. AB - Over the past 20 years, the role of psychological and social factors, including the physician-patient working alliance, have emerged as integral components of medical care for patients with a myriad of health conditions. The current study examines a model comprised of psychological-interpersonal factors and the extent to which it explains patient satisfaction with and adherence to hemodialysis treatment. One hundred and seven adults with end-stage renal disease who were receiving regular outpatient hemodialysis participated in the study. Path analyses show that the physician-patient working alliance indirectly predicts patient adherence through patient satisfaction and patients' outcome expectations. The working alliance directly predicts patients' quality of life. It is concluded that consistent with previous research, the physician-patient working alliance is a significant factor in predicting key patient behaviors in medical care. PMID- 26808408 TI - Directed Growth of Metal-Organic Frameworks and Their Derived Carbon-Based Network for Efficient Electrocatalytic Oxygen Reduction. AB - A honeycomb-like carbon-based network is obtained by in situ nucleation and directed growth of metal-organic framework (MOF) arrays on the surface of layered double hydroxide (LDH) nanoplatelets, followed by a subsequent pyrolysis process, which exhibits largely enhanced electrocatalytic ORR performances. A successful paradigm for the directed growth of highly oriented MOF arrays is demonstrated, with potential applications for energy storage and conversion. PMID- 26808409 TI - In Vitro Evaluation of Inhalable Verapamil-Rifapentine Particles for Tuberculosis Therapy. AB - Recent studies have demonstrated that efflux pumps of Mycobacterium tuberculosis (M. tb) provide a crucial mechanism in the development of drug resistant to antimycobacterial drugs. Drugs that inhibit these efflux pumps, such as verapamil, have shown the potential in enhancing the treatment success. We therefore hypothesized that the combined inhaled administration of verapamil and a first-line rifamycin antibiotic will further improve the treatment efficacy. An inhalable dry powder consisting of amorphous verapamil and crystalline rifapentine with l-leucine as an excipient was produced by spray drying. The in vitro aerosol characteristic of the powder, its microbiological activity and stability were assessed. When the powder was dispersed by an Osmohaler, the total fine particle fraction (FPFtotal, wt % of particles in aerosol <5 MUm) of verapamil and rifapentine was 77.4 +/- 1.1% and 71.5 +/- 2.0%, respectively. The combination drug formulation showed a minimum inhibitory concentration (MIC90) similar to that of rifapentine alone when tested against both M. tb H37Ra and M. tb H37Rv strains. Importantly, the combination resulted in increased killing of M. tb H37Ra within the infected macrophage cells compared to either verapamil or rifapentine alone. In assessing cellular toxicity, the combination exhibited an acceptable half maximal inhibitory concentration (IC50) values (62.5 MUg/mL) on both human monocytic (THP-1) and lung alveolar basal epithelial (A549) cell lines. Finally, the powder was stable after 3 months storage in 0% relative humidity at 20 +/- 3 degrees C. PMID- 26808410 TI - Distribution of T Cells in Rainbow Trout (Oncorhynchus mykiss) Skin and Responsiveness to Viral Infection. AB - Although the skin constitutes the first line of defense against waterborne pathogens, there is a great lack of information regarding the skin associated lymphoid tissue (SALT) and whether immune components of the skin are homogeneously distributed through the surface of the fish is still unknown. In the current work, we have analyzed the transcription of several immune genes throughout different rainbow trout (Oncorhynchus mykiss) skin areas. We found that immunoglobulin and chemokine gene transcription levels were higher in a skin area close to the gills. Furthermore, this skin area as well as other anterior sections also transcribed significantly higher levels of many different immune genes related to T cell immunity such as T cell receptor alpha (TCRalpha), TCRgamma, CD3, CD4, CD8, perforin, GATA3, Tbet, FoxP3, interferon gamma (IFNgamma), CD40L and Eomes in comparison to posterior skin sections. In agreement with these results, immunohistochemical analysis revealed that anterior skin areas had a higher concentration of CD3(+) T cells and flow cytometry analysis confirmed that the percentage of CD8(+) T lymphocytes was also higher in anterior skin sections. These results demonstrate for the first time that T cells are not homogeneously distributed throughout the teleost skin. Additionally, we studied the transcriptional regulation of these and additional T cell markers in response to a bath infection with viral hemorrhagic septicemia virus (VHSV). We found that VHSV regulated the transcription of several of these T cell markers in both the skin and the spleen; with some differences between anterior and posterior skin sections. Altogether, our results point to skin T cells as major players of teleost skin immunity in response to waterborne viral infections. PMID- 26808411 TI - MAGP2 controls Notch via interactions with RGD binding integrins: Identification of a novel ECM-integrin-Notch signaling axis. AB - Canonical Notch signaling involves Notch receptor activation via interaction with cell surface bound Notch ligand. Recent findings also indicate that Notch signaling may be modulated by cross-talk with other signaling mechanisms. The ECM protein MAGP2 was previously shown to regulate Notch in a cell type dependent manner, although the molecular details of this interaction have not been dissected. Here, we report that MAGP2 cell type specific control of Notch is independent of individual Notch receptor-ligand combinations but dependent on interaction with RGD binding integrins. Overexpressed MAGP2 was found to suppress transcriptional activity from the Notch responsive Hes1 promoter activity in endothelial cells, while overexpression of a RGD->RGE MAGP2 mutant increased Notch signaling in the same cell type. This effect was not unique to MAGP2 since the RGD domain of the ECM protein EGFL7 was also found to be an important modulator of Hes1 promoter activity. Independently of MAGP2 or EGFL7, inhibition of RGD-binding integrins with soluble RGD peptides also increased accumulation of active N1ICD fragments and Notch responsive promoter activity independently of changes in Notch1, Jag1, or Dll4 expression. Finally, beta1 or beta3 integrin blocking antibodies also enhanced Notch signaling. Collectively, these results answer the question of how MAGP2 controls cell type dependent Notch signaling, but more importantly uncover a new mechanism to understand how extracellular matrices and cellular environments impact Notch signaling. PMID- 26808412 TI - Metabolic alterations in bladder cancer: applications for cancer imaging. AB - Treatment planning, outcome and prognosis are strongly related to the adequate tumor staging for bladder cancer (BC). Unfortunately, a large discrepancy exists between the preoperative clinical and final pathologic staging. Therefore, an advanced imaging-based technique is crucial for adequate staging. Although Magnetic Resonance Imaging (MRI) is currently the best in vivo imaging technique for BC staging because of its excellent soft-tissue contrast and absence of ionizing radiation it lacks cancer-specificity. Tumor-specific positron emission tomography (PET), which is based on the Warburg effect (preferential uptake of glucose by cancer cells), exploits the radioactively-labeled glucose analogs, i.e., FDG. Although FDG-PET is highly cancer specific, it lacks resolution and contrast quality comparable with MRI. Chemical Exchange Saturation Transfer (CEST) MRI enables the detection of low concentrations of metabolites containing protons. BC is an attractive target for glucose CEST MRI because, in addition to the typical systemic administration, glucose might also be directly applied into the bladder to reduce toxicity-related complications. As a first stage of the development of a contrast-specific BC imaging technique we have studied glucose uptake by bladder epithelial cells and have observed that glucose is, indeed, consumed by BC cells with higher intensity than by non-transformed urothelial cells. This effect might be partly explained by increased expression of glucose transporters GLUT1 and GLUT3 in transformed cells as compared to normal urothelium. We also detected higher lactate production by BC cells which is another cancer-specific manifestation of the Warburg effect. In addition, we have observed other metabolic alterations in BC cells as compared to non-transformed cells: in particular, increased pyruvate synthesis. When glucose was substituted by glutamine in culture media, preferential uptake of glutamine by BC cells was observed. The preferential uptake of glucose by BC cells gives an opportunity to develop NMR based imaging procedures where glucose or its derivatives can serve as a contrasting agent. In addition, metabolic alterations observed in BC cells could provide the basis for development of new anti-cancer therapeutics. PMID- 26808413 TI - Clinical and genetic characterization of patients with hypertrophic cardiomyopathy and right atrial enlargement. AB - AIMS: Prevalence and clinical significance of right atrial enlargement (RAE) has been poorly characterized in hypertrophic cardiomyopathy. METHODS: One hundred and sixty consecutive patients with hypertrophic cardiomyopathy (35.5 +/- 20 years; 64% men) were studied. They underwent clinical examination, standard ECG, M-mode, 2D and Doppler echocardiography, stress test and ECG Holter monitoring. Major adverse cardiac events were considered: cardiac death (sudden death, heart failure death); cardiac transplant; resuscitated cardiac arrest or appropriate implantable cardioverter defibrillator discharge. Genetic analysis of eight sarcomeric genes was performed using Sanger sequencing. RESULTS: RAE was observed in 22 patients (14%), associated with left atrial enlargement in all cases. Patients with RAE were likely to have restrictive mitral pattern (P < 0.001) and had higher New York Heart Association (P < 0.001), N-terminal prohormone of brain natriuretic peptide (P < 0.001), left atrial volume index (P < 0.001), lateral (P = 0.04) and septal (P = 0.002) E/e', systolic pulmonary artery pressure (P < 0.001) and lower ejection fraction (all P < 0.001). On cardiopulmonary exercise testing, peak VO2 was lower and VE/VCO2 higher in patients with RAE (P < 0.001). During a mean follow-up of 4 +/- 2.1 years, 30 major adverse cardiac events in 24 patients (15%) were observed. Cox proportional hazards regression analysis identified RAE as an independent predictor of major adverse cardiac events (odds ratio = 2.6; confidence interval 1.5-4.6; P = 0.001). In patients with RAE who were genetically tested, there was a higher prevalence of sarcomeric gene mutations (68%), double mutations (16%) and troponin T mutations (21%). CONCLUSION: RAE is present in a small subset of patients with hypertrophic cardiomyopathy, and largely reflects increased pulmonary pressures because of severe diastolic and/or systolic left ventricular dysfunction. Patients with RAE had a higher prevalence of sarcomeric gene mutations, troponin T mutations and complex genotypes. In conclusion, RAE may serve as a very useful marker of disease progression and adverse outcome in patients with sarcomeric hypertrophic cardiomyopathy. PMID- 26808414 TI - Isolation of the left innominate artery: a question of connection. PMID- 26808415 TI - Does stem cell therapy induce myocardial neoangiogenesis? Histological evaluation in an ischemia/reperfusion animal model. AB - BACKGROUND: In an experimental model in the rabbit, a myocardial ischemia reperfusion injury was obtained. Subsequently, the effects of homologous bone marrow stem cell (BMSC) administration were studied. METHODS: In 21 New Zealand adult rabbits, ischemia/reperfusion damage was induced by temporary occlusion of the anterior descending coronary artery. Homologous BMSCs were isolated, cultured and re-suspended for injection at the level of the ischemic zone. We evaluated the proangiogenetic effect of intramyocardial injections of BMSC at the peri infarcted area. Histological evaluations were made after 20 days from the surgical procedure. RESULTS: In rabbits treated with intramyocardial BMSC administration, we demonstrated histologically capillary neoangiogenesis, without signs of tissue immunological reaction or of generation of new myocardial cells. On the contrary, only minimal neovascular supply was detected in rabbits treated with intravenous administration of BMSC. Only typical signs of ischemic myocardium injury were observed in the control group. CONCLUSION: These observations suggest that the effect of direct BMSC administration in ischemic myocardium could promote a capillary neoangiogenesis, which helps to prevent ischemic myocardial damage. PMID- 26808416 TI - What's new in 2015 ESC guidelines on pericardial diseases? PMID- 26808417 TI - Causes of death and mortality in hypertrophic cardiomyopathy patients with implantable defibrillators in Sweden. AB - AIMS: Implantable defibrillators (ICDs) successfully terminate ventricular arrhythmias in hypertrophic cardiomyopathy (HCM), protect against bradycardia, and monitor atrial arrhythmias. This may alter the natural history and causes of death. METHODS: This nationwide observational longitudinal retrospective study of all HCM patients implanted during 1995-2012 obtained data from the Swedish ICD Registry, the National Patient Register, the Cause of Death Register, and were validated by review of medical records. RESULTS: Of 342 patients (mean age 51.8 years, 70.8% males), 45 died during a total follow-up of 1847 years (mean 5.4 years). Mean age at death was 68.2 years (range 21-83 years; 12 were >=75 years). Mean follow-up time among the deceased was 4.9 years (quartiles 1.4-7.4 years). All-cause mortality was higher in HCM patients compared with the age and sex matched Swedish general population (standardized mortality ratio 3.4; 95% confidence interval 2.4-4.5; P < 0.001). Main cause of death was heart failure (n = 27), stroke (n = 5), cancer (n = 3), myocardial infarction (n = 2), sepsis (n = 2), and others (n = 4). Two patients died suddenly, one after the ICD was turned off because of inappropriate shocks, and one patient whose device system was removed after infection. HCM was the main cause of death in 76% of the cases, mainly because of progressive heart failure. CONCLUSION: For HCM patients, ICDs almost eliminate premature arrhythmic death and result in a shift to heart failure as the cause of death in the majority of cases. Still, mortality in HCM patients remains elevated and management of heart failure and comorbidities must be improved to increase survival. PMID- 26808418 TI - Triple Burden of Obesity, Undernutrition, and Cardiovascular Disease Risk among Indian Tribes. AB - BACKGROUND: Socio-cultural transitions among individuals from vulnerable groups introduce epidemiological transition, with a concomitant increase in the prevalence of undernutrition, obesity, and cardiovascular disease risks. An accepted conventional wisdom exists for Indian tribes that they are undernourished and away from lifestyle-related diseases. However, the extent of this triple burden affecting them is unknown. In this study, we assessed this triple burden among the 9 major tribes of India. METHODS AND FINDINGS: During January 2011 to December 2013, we conducted a cross-sectional study among 1066 men and 1090 women constituting a total of 2156 adults belonging to the 9 major tribal groups: Santals, Oraons, and Koras (West Bengal); Santals, Bhumijs, and Bathudis (Odisha); and Dhodias, Kuknas, and Chaudharis (Gujarat) to estimate the prevalence of the triple burden (undernutrition, overweight or obesity, and hypertension). A high prevalence of undernutrition and hypertension was observed among the Koras (51.9%and 10.6%, respectively), Bathudis (51.3% and 12.1%, respectively), and Oraons (49.6% and 16.5%, respectively). However, the prevalence of overweight and hypertension among the Bhumijs (17.7% and 14.7%, respectively), Dhodias (23.8% and 12.9%, respectively), Kuknas (15.8% and 11.3%, respectively), and Santals of West Bengal (12.2% and 11.8%, respectively) and Odisha (15% and 9.6%, respectively) was most alarming. The prevalence of overweight or obesity among the women was 10.9% and 1.5%, respectively, with 14.0% hypertensive women. The prevalence of overweight and obesity among the men was 14.8% and 1.7%, respectively, with 9.2% hypertensive men. Undernutrition was highly prevalent among men and women. However, data from the past 30 years on systolic blood pressure (SBP) and body mass index (BMI) revealed that the studied tribes were at a higher risk than the general Indian population. In addition, a vast gender disparity with relation to the disease and risk prevalence was observed. CONCLUSION: The alarming trend of an increasing prevalence of overweight/obesity, undernutrition, and hypertension is observed among indigenous populations of India, emphasizing the incorporation of a specific health management policy. PMID- 26808420 TI - Diagnostic validity of line bisection in the acute phase of stroke. AB - The line bisection task is commonly depicted as a valid diagnostic tool to help differentiate between primary visual field defects and spatial neglect. However, recent studies have addressed possible drawbacks in the acute phase after stroke onset. We investigated these critical assumptions in a large and homogeneous sample of 180 acute stroke patients. Line bisection, cancellation performance, copying, and primary visual field defects were assessed in 180 acute right hemispheric stroke patients. Effects of visual field defects and concurrent spatial neglect on line bisection were analyzed by multiple regression to account for possible additive and interactive effects. The relation between line bisection and other tests applied in spatial neglect was explored by factorial analysis. We found no evidence for the existence of a contralesional 'hemianopic line bisection error' in acute patients with primary visual field defects. Such patients even showed a more pronounced ipsilesional line bisection error. Second, the factorial analysis revealed that the line bisection task on the one hand and cancellation/copying tasks on the other were represented by different factors, indicating that they make different cognitive demands. In the acute phase of stroke, line bisection does not appear to be a valid task to diagnose neither primary visual field defects nor spatial neglect (the latter as defined by its core symptoms (cf., Karnath and Rorden, 2012) which are typically captured with cancellation/copying tasks). PMID- 26808419 TI - Scaling factors for the in vitro-in vivo extrapolation (IV-IVE) of renal drug and xenobiotic glucuronidation clearance. AB - AIM: To determine the scaling factors required for inclusion of renal drug glucuronidation clearance in the prediction of total clearance via glucuronidation (CLUGT ). METHODS: Microsomal protein per gram of kidney (MPPGK) was determined for human 'mixed' kidney (n = 5) microsomes (MKM). The glucuronidation activities of deferiprone (DEF), propofol (PRO) and zidovudine (AZT) by MKM and paired cortical (KCM) and medullary (KMM) microsomes were measured, along with the UGT 1A6, 1A9 and 2B7 protein contents of each enzyme source. Unbound intrinsic clearances (CLint,u,UGT ) for PRO and morphine (MOR; 3- and 6-) glucuronidation by MKM, human liver microsomes (HLM) and recombinant UGT1A9 and 2B7 were additionally determined. Data were scaled using in vitro-in vivo extrapolation (IV-IVE) approaches to assess the influence of renal CLint,u,UGT on the prediction accuracy of the calculated CLUGT values of PRO and MOR. RESULTS: MPPGK was 9.3 +/- 2.0 mg g(-1) (mean +/- SD). The respective rates of DEF (UGT1A6), PRO (UGT1A9) and AZT (UGT2B7) glucuronidation by KCM were 1.4-, 5.2- and 10.5-fold higher than those for KMM. UGT 1A6, 1A9 and 2B7 were the only enzymes expressed in kidney. Consistent with the activity data, the abundance of each of these enzymes was greater in KCM than in KMM. The abundance of UGT1A9 in MKM (61.3 pmol mg(-1) ) was 2.7 fold higher than that reported for HLM. CONCLUSIONS: Scaled renal PRO glucuronidation CLint,u,UGT was double that of liver. Renal CLint,u,UGT should be accounted for in the IV-IVE of UGT1A9 and considered for UGT1A6 and 2B7 substrates. PMID- 26808422 TI - The use of Zostavax in Spain: the economic case for vaccination of individuals aged 50 years and older. AB - Background Population aging brings up a number of health issues, one of which is an increased incidence of herpes zoster (HZ) and its complication, post-herpetic neuralgia (PHN). Zostavax vaccine has recently become available to prevent HZ and PHN. This study evaluates the cost-effectiveness of vaccination against HZ in Spain considering a vaccination of the population aged 50 years and older and comparing this to the current situation where no vaccination is being administered. Methods An existing, validated, and published economic model was adapted to Spain using relevant local input parameters and costs from 2013. Results Vaccinating 30% of the Spanish population aged 50 years and older resulted in ?16,577/QALY gained, ?2025/HZ case avoided, and ?5594/PHN case avoided under the third-party payer perspective. From a societal perspective, the ICERs increased by 6%, due to the higher price of the vaccine. The number needed to vaccinate to prevent one case was 20 for HZ, and 63 for PHN3. Sensitivity analyses showed that the model was most sensitive to the HZ and PHN epidemiological data, the health state utilities values, and vaccine price used. Conclusion Considering an acceptable range of cost-effectiveness of ?30,000 ?50,000 per QALY gained, vaccination of the 50+ population in Spain against HZ with a new vaccine, Zostavax, is cost-effective and makes good use of the valuable healthcare budget. PMID- 26808421 TI - Improved Pancreatic Adenocarcinoma Diagnosis in Jaundiced and Non-Jaundiced Pancreatic Adenocarcinoma Patients through the Combination of Routine Clinical Markers Associated to Pancreatic Adenocarcinoma Pathophysiology. AB - BACKGROUND: There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies. METHODS: CA 19-9, carcinoembryonic antigen (CEA), C-reactive protein, albumin, insulin growth factor-1 (IGF-1) and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls. RESULTS: The combination of CA 19 9, IGF-1 and albumin resulted in a combined area under the curve (AUC) of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19-9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients. CONCLUSIONS: Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis. PMID- 26808423 TI - Using the Hexaploid Nature of Wheat To Create Variability in Starch Characteristics. AB - In hexaploid crops, such as bread wheat, it should be possible to fine-tune phenotypic traits by identifying wild-type and null genes from each of the three genomes and combining them in a calculated manner. Here, we demonstrate this with gene combinations for two starch synthesis genes, SSIIa and GBSSI. Lines with inactive copies of both enzymes show a very dramatic change in phenotype, so to create intermediate phenotypes, we used marker-assisted selection to develop near isogenic lines (NILs) carrying homozygous combinations of null alleles. For both genes, gene dosage effects follow the order B > D >= A; therefore, we completed detailed analysis of starch characteristics for NIL 3-3, which is null for the B genome copy of the SSIIa and GBSSI genes, and NIL 5-5, which has null mutations in the B- and D-genome-encoded copies of both of these genes. The effects of the combinations on phenotypic traits followed the order expected on the basis of genotype, with NIL 5-5 showing the largest differences from the wild type, while NIL 3-3 characteristics were intermediate between NIL 5-5 and the wild type. Differences among genotypes were significant for many starch characteristics, including percent amylose, chain length distribution, gelatinization temperature, retrogradation, and pasting properties, and these differences appeared to translate into improvements in end-product quality, since bread made from type 5 5 flour showed a 3 day lag in staling. PMID- 26808424 TI - Correction: Elevated Concentrations of Serum Immunoglobulin Free Light Chains in Systemic Lupus Erythematosus Patients in Relation to Disease Activity, Inflammatory Status, B Cell Activity and Epstein-Barr Virus Antibodies. PMID- 26808425 TI - A structured assessment of motor function and behavior in patients with Kleefstra syndrome. AB - The present study aimed to further our understanding of Kleefstra syndrome, especially regarding motor function and behavioral characteristics. In total, four males and four females between two and 27 years of age with a genetically confirmed diagnosis of Kleefstra syndrome and their parents participated in this study. Four patients had 9q34.3 deletions that caused Euchromatin Histone Methyl Transferase 1 (EHMT1) haplo-insufficiency, and four patients harbored EHMT1 mutations. The motor function was evaluated via systematic observation. Standardized assessments such as the Vineland Adapted Behavior Scales II (VABS II), the Social Communication Questionnaire (SCQ) and the Child or Adult Behavior Checklist (CBCL, ABCL) were used for the behavioral assessment. All patients showed a delayed developmental status. Muscular hypotonia and its manifestations were present in all patients, regardless of their age. The mean values for all VABS II domains (communication, socialization, daily living skills, and motor skills) were significantly lower than the mean of the reference population (p < 0.001), but similar to other rare intellectual disabilities such as Smith-Magenis syndrome and Angelman syndrome. The results from the SCQ indicated that all patient values exceeded the cut-off value, suggesting the possibility of autism spectrum disorder. The behavioral and emotional problems assessed by CBCL and ABCL were less frequent. In conclusion, patients with Kleefstra syndrome present with a broad range of clinical problems in all age groups and are therefore in need of a multidisciplinary follow-up also after their transition into adulthood. PMID- 26808426 TI - Novel VIPAS39 mutation in a syndromic patient with arthrogryposis, renal tubular dysfunction and intrahepatic cholestasis. AB - ARC syndrome is a rare autosomal recessive disease, characterized by arthrogryposis, renal tubular dysfunction and cholestasis. Herein a 2.5 month old infant with dysmorphic features, including small anterior fontanel, low set ears, beaked nose and high arched palate is presented who was referred because of icterus. He also suffered from some additional anomalies, including unilateral choanal atresia, club foot, and bilateral developmental dislocation of hip, while further studies showed renal tubular acidosis and hearing impairment in addition to cholestasis. Genetic studies showed a homozygous mutation in the VIPAS39 gene. Making the definite diagnosis of the syndrome is important, while increased risk of mutation in other siblings highlights the importance of prenatal diagnosis. PMID- 26808427 TI - Belief in Food Addiction and Obesity-Related Policy Support. AB - OBJECTIVES: This study examines whether belief in the food addiction construct is associated with support for obesity-related policies (e.g., restrictions on foods served in schools and workplace cafeterias, subsidies on fruits and vegetables), while simultaneously examining other factors associated with policy support (e.g., political party affiliation). DESIGN: Cross-sectional. SETTING: Online Community. PARTICIPANTS: 200 individuals were recruited through Amazon Mechanical Turk. MEASUREMENTS: Participants (n = 193) responded to three questions about belief in food addiction and a measure evaluating support for 13 obesity-related policy initiatives. Individuals also completed the modified Yale Food Addiction Scale (mYFAS), self-reported height and weight, and provided demographic information (age, gender, race, political party affiliation). RESULTS: Belief in food addiction was significantly associated with greater support for obesity related initiatives, even when accounting for the significant associations of age, gender, and political party. Belief in food addiction and political party both had moderate effect sizes for predicting support for obesity-related policy. There was an interaction between age and belief in food addiction, with significant associations with policy support for both younger and older individuals, though the effect was larger for younger participants. CONCLUSION: The current study provides evidence that belief in food addiction is associated with increased obesity-related policy support, comparable to the influence of one's political party. Growing evidence for the role of an addictive process in obesity may have important implications for public support of obesity-related policy initiatives. PMID- 26808428 TI - Incidence and Variation of Discrepancies in Recording Chronic Conditions in Australian Hospital Administrative Data. AB - Diagnostic data routinely collected for hospital admitted patients and used for case-mix adjustment in care provider comparisons and reimbursement are prone to biases. We aim to measure discrepancies, variations and associated factors in recorded chronic morbidities for hospital admitted patients in New South Wales (NSW), Australia. Of all admissions between July 2010 and June 2014 in all NSW public and private acute hospitals, admissions with over 24 hours stay and one or more of the chronic conditions of diabetes, smoking, hepatitis, HIV, and hypertension were included. The incidence of a non-recorded chronic condition in an admission occurring after the first admission with a recorded chronic condition (index admission) was considered as a discrepancy. Poisson models were employed to (i) derive adjusted discrepancy incidence rates (IR) and rate ratios (IRR) accounting for patient, admission, comorbidity and hospital characteristics and (ii) quantify variation in rates among hospitals. The discrepancy incidence rate was highest for hypertension (51% of 262,664 admissions), followed by hepatitis (37% of 12,107), smoking (33% of 548,965), HIV (27% of 1500) and diabetes (19% of 228,687). Adjusted rates for all conditions declined over the four-year period; with the sharpest drop of over 80% for diabetes (47.7% in 2010 vs. 7.3% in 2014), and 20% to 55% for the other conditions. Discrepancies were more common in private hospitals and smaller public hospitals. Inter-hospital differences were responsible for 1% (HIV) to 9.4% (smoking) of variation in adjusted discrepancy incidences, with an increasing trend for diabetes and HIV. Chronic conditions are recorded inconsistently in hospital administrative datasets, and hospitals contribute to the discrepancies. Adjustment for patterns and stratification in risk adjustments; and furthermore longitudinal accumulation of clinical data at patient level, refinement of clinical coding systems and standardisation of comorbidity recording across hospitals would enhance accuracy of datasets and validity of case-mix adjustment. PMID- 26808429 TI - Quantifying Oldowan Stone Tool Production at Olduvai Gorge, Tanzania. AB - Recent research suggests that variation exists among and between Oldowan stone tool assemblages. Oldowan variation might represent differential constraints on raw materials used to produce these stone implements. Alternatively, variation among Oldowan assemblages could represent different methods that Oldowan producing hominins utilized to produce these lithic implements. Identifying differential patterns of stone tool production within the Oldowan has implications for assessing how stone tool technology evolved, how traditions of lithic production might have been culturally transmitted, and for defining the timing and scope of these evolutionary events. At present there is no null model to predict what morphological variation in the Oldowan should look like. Without such a model, quantifying whether Oldowan assemblages vary due to raw material constraints or whether they vary due to differences in production technique is not possible. This research establishes a null model for Oldowan lithic artifact morphological variation. To establish these expectations this research 1) models the expected range of variation through large scale reduction experiments, 2) develops an algorithm to categorize archaeological flakes based on how they are produced, and 3) statistically assesses the methods of production behavior used by Oldowan producing hominins at the site of DK from Olduvai Gorge, Tanzania via the experimental model. Results indicate that a subset of quartzite flakes deviate from the null expectations in a manner that demonstrates efficiency in flake manufacture, while some basalt flakes deviate from null expectations in a manner that demonstrates inefficiency in flake manufacture. The simultaneous presence of efficiency in stone tool production for one raw material (quartzite) and inefficiency in stone tool production for another raw material (basalt) suggests that Oldowan producing hominins at DK were able to mediate the economic costs associated with stone tool procurement by utilizing high-cost materials more efficiently than is expected and low-cost materials in an inefficient manner. PMID- 26808430 TI - Surveillance of Physicians Causing Potential Drug-Drug Interactions in Ambulatory Care: A Pilot Study in Switzerland. AB - OBJECTIVES: We analysed potential drug-drug interactions (DDI) in ambulatory care in Switzerland based on claims data from three large health insurers in 2010 to identify physicians with peculiar prescription behaviour differing from peers of the same specialty. METHODS: We analysed contraindicated or potentially contraindicated DDI from the national drug formulary and calculated for each physician the ratios of the number of patients with a potential DDI divided by the number of patients at risk and used a zero inflated binomial distribution to correct for the inflated number of observations with no DDI. We then calculated the probability that the number of caused potential DDI of physicians was unlikely (p-value < 0.05 and >= 0.01) and very unlikely (p-value <0.01) to be due to chance. RESULTS: Of 1'607'233 females and 1'525'307 males 1.3% and 1.2% were exposed to at least one potential DDI during 12 months. When analysing the 40 most common DDI, 598 and 416 of 18,297 physicians (3.3% and 2.3%) were causing potential DDI in a frequency unlikely (p<0.05 and p >= 0.01) and very unlikely (p<0.01) to be explained by chance. Patients cared by general practitioners and cardiologists had the lowest probability (0.20 and 0.26) for not being exposed to DDI. CONCLUSIONS: Contraindicated or potentially contraindicated DDI are frequent in ambulatory care in Switzerland, with a small proportion of physicians causing potential DDI in a frequency that is very unlikely to be explained by chance when compared to peers of the same specialty. PMID- 26808431 TI - Seizures as a Consequence of Hyperviscosity Syndrome in Two Dogs Naturally Infected with Leishmania infantum. AB - Serum hyperviscosity syndrome (HVS) was documented in two dogs with canine leishmaniasis (CanL) and seizures as the major clinical complaint. In both cases, laboratory abnormalities included mild non-regenerative anemia, thrombocytopenia, hypoalbuminemia, hyperproteinemia with monoclonal gammopathy, and marked serum hyperviscosity. CanL was diagnosed using cytology in one case and indirect immunofluorescence assay and conventional polymerase chain reaction in the second. Specific therapy with meglumine antimoniate and allopurinol(c) led to short-term remission in both dogs and normalization of serum viscosity. Although dogs rarely develop HVS, it should be suspected if hyperproteinemia and monoclonal gammopathy are present. Since CanL manifests with a variety of clinical presentations, including seizures resulting from HVS-induced central nervous system hypoxia, it should also be considered as a differential diagnosis in animals with seizures as a primary presenting sign. PMID- 26808432 TI - Canine Cutaneous and Subcutaneous Soft Tissue Sarcoma: An Evidence-Based Review of Case Management. AB - Canine cutaneous and subcutaneous soft tissue sarcomas (STS) account for 20.3% of malignant neoplasms of the skin. This article makes recommendations for the diagnosis, treatment, and follow-up in dogs with STS, using evidence-based medicine concepts. Although our review of the literature on the management of canine STS found many of the studies to be less than rigorous, board-certified specialists in internal medicine, surgery, pathology, oncology, and radiation oncology were able to make several recommendations based on the literature review: cytology and biopsy are important for presurgical planning; wide (>3 cm margins) surgical excision decreases the likelihood of tumor recurrence; the use of a histologic grading scale is useful in predicting biologic behavior; and, in select cases, chemotherapy and radiation therapy may be beneficial adjunct treatments to surgical excision. More research is necessary to determine minimum size of surgical margins, the impact of radiation therapy on incompletely resected tumors, the ideal chemotherapy protocol for high grade STS, and the optimal methods of monitoring dogs for tumor recurrence and metastasis. PMID- 26808433 TI - Comparison of Glucosamine Absorption After Administration of Oral Liquid, Chewable, and Tablet Formulations to Dogs. AB - Glucosamine (GS) is commonly administered as a nutritional supplement to support joint function. Although many supplements are available, the effect of formulation on oral absorption in dogs is unknown. The purpose of this study was to determine the relative bioavailability of GS for liquid, chewable, and tablet formulations containing GS sulfate or hydrochloride and chondroitin sulfate. In a randomized cross-over design, supplements were administered daily for 8 days with a 1 wk washout period between treatments. Liquid or Tablet A was administered to four dogs, whereas Liquid or Tablet B was administered to four additional dogs. When nutraceutical exposure was normalized to the administered dose of GS free base, similar relative bioavailabilities were determined for all three formulations. However, the dose-normalized maximum plasma GS concentration was higher for the liquid supplement (5.5 +/- 0.5 MUg/mL) than for the two tablets (3.1 +/- 0.6 and 2.1 +/- 0.6 MUg/mL, P < 0.001). Similarly, the time at which maximal plasma GS concentrations occurred was shorter for the liquid formulation (0.7 +/- 0.5 hr) than for the two tablets (4.2 +/- 0.6 and 5.0 +/- 0.6 hr, P < 0.001). These data show that the formulation of joint supplements affects the oral absorption of GS in dogs. PMID- 26808434 TI - Prophylactic Gastropexy Incorporating a Gastrotomy Incision in Dogs: A Retrospective Study of 21 Cases (2011-2013). AB - The objective of this retrospective study was to report any complications associated with incorporating a gastrotomy incision into a right-sided incisional prophylactic gastropexy. The medical records of dogs that underwent a gastrotomy for the removal of gastric foreign material and had a prophylactic right-sided incisional gastropexy performed at the gastrotomy site between April 2011 and February 2013 were reviewed. Two wk postoperative recheck examination and suture removal reports were reviewed and owners were contacted via phone and e-mail for long-term follow-up. In total, 21 cases were reviewed, 19 with long-term follow up. No complications of the surgery were reported. We concluded that a prophylactic right-sided incisional gastropexy could successfully be performed incorporating the gastrotomy site without significant complications. PMID- 26808435 TI - Evaluation of Bacterial Contamination of Clipper Blades in Small Animal Private Practice. AB - Nosocomial infections are a growing concern in veterinary hospitals, and identifying fomites is imperative to reducing the risk of pathogen transmission. In veterinary medicine, shaving of hair is necessary prior to many procedures. Contaminated clipper blades have been cited as potential fomites involved in the transmission of pathogens in veterinary and human medicine. The primary goal of this study was to evaluate bacterial contamination of clipper blades in veterinary practices. A secondary goal was to assess whether there was an association between bacterial contamination of clipper blades and clipper blade cleaning solutions, clipper blade cleaning protocols, clipper blade storage, and type of practice. Sixty clipper blades from 60 different practices were cultured. Information regarding blade cleaning solutions, protocols, and storage was collected from each practice. Fifty-one percent (31/60) of clipper blades sampled were contaminated with bacteria. Category of cleaning solutions had a significant association with bacterial contamination (P < 0.02). Cleaning frequency (P = 0.55), storage location (P = 0.26), and practice type (P = 0.06) had no significant association with bacterial contamination. This study documented bacterial contamination of clipper blades in veterinary practices, and clipper blades should be considered potential fomites. PMID- 26808436 TI - Evaluating Femoral-Sciatic Nerve Blocks, Epidural Analgesia, and No Use of Regional Analgesia in Dogs Undergoing Tibia-Plateau-Leveling-Osteotomy. AB - This is a retrospective study evaluating femoral-sciatic nerve blocks (FSBs), epidural analgesia, and non-regional analgesia (NRA) in dogs undergoing tibia plateau-leveling-osteotomy surgery. Thirty-five records met the criteria for each of the FSB and epidural analgesia groups. Seventeen anesthesia records met the criteria for the NRA or control group. The parameters reported were: isoflurane vaporizer setting, rescue analgesia/anesthesia drugs received, heart rate, systolic blood pressure, and recovery quality (0-4, with 0 being poor and 4 being good). Rescue analgesia-anesthesia during surgery was performed with either fentanyl, ketamine, or propofol. A larger percentage of dogs in the NRA group required rescue analgesia during surgery. The FSB group had a higher recovery quality with median (95% confidence interval of four (+/-0.3) when compared to two (+/-0.8) in NRA (p < 0.01). No difference between groups was observed on any other parameter reported. As part of a multimodal analgesia approach for tibia plateau-leveling-osteotomy surgery, the use of femoral and sciatic nerves blocks with bupivacaine appears to be an alternative technique to help with analgesia and anesthesia during surgery. PMID- 26808437 TI - Short-Term Radiographic Complications and Healing Assessment of Single-Session Bilateral Tibial Tuberosity Advancements. AB - The objective of this study is to report on the short-term radiographic complications and bone healing associated with single-session bilateral tibial tuberosity advancements (TTAs). This retrospective study consists of 74 client owned dogs with bilateral cranial cruciate ligament rupture that underwent consecutive single-session bilateral TTAs. Radiographs from 74 dogs (148 stifles) were evaluated for evidence of postoperative complications. One hundred forty three of 148 stifles were scored for radiographic healing using a previously described scoring system. Variables evaluated for a relationship with radiographic complications and healing scores were: breed, age, body weight, sex, and TTA plate type. The overall radiographic complication rate was 17.6% (13/74). Twelve of the 13 radiographic complications were considered to be minor and one was major. Increasing body weight and use of a fork implant were statistically significant factors associated with an increased risk of complication. One hundred forty-three stifle radiographs met the inclusion criteria to be assessed for healing. The mean score was 2.96 out of 4.0. The overall radiographic complication rate and healing scores associated with single-session bilateral TTAs were found to be similar to those described for unilateral TTA. PMID- 26808439 TI - Impact of Whole-Blood Processing Conditions on Plasma and Serum Concentrations of Cytokines. AB - Pre-analytical variations in plasma and serum samples can occur because of variability in whole-blood processing procedures. The aim of this study was to determine the impact of delayed separation of whole blood on the plasma and serum concentrations of cytokines. The concentrations of 16 cytokines were measured in plasma and serum samples when the centrifugation of whole blood at room temperature was delayed for 4, 6, 24, or 48 h, and the values were compared with those observed after separation within 2 h of whole-blood collection. Receiver operating characteristic (ROC) curve analysis was also performed for cytokines to determine whether cytokine levels in plasma and serum samples can be used to assess delayed separation of whole blood. Plasma concentrations of interleukin (IL)-1beta, granulocyte-macrophage colony-stimulating factor (GM-CSF), and soluble CD40 ligand (sCD40L) and serum concentrations of IL-1beta, IL-6, IL-8, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta increased significantly (>2-fold) when separation was delayed at room temperature for 24 h. The concentrations of 6 of these cytokines (all except serum IL-1beta and IL-6) demonstrated high diagnostic performance (area under the ROC curve >0.8) for delayed separation of whole blood. Furthermore, these cytokine concentrations typically exhibited high sensitivity and specificity at each optimal cutoff point. Conversely, IL-17A was stable in both plasma and serum samples, even when whole-blood centrifugation was delayed at room temperature for 48 h. This study shows that certain cytokines (IL-1beta, GM-CSF, sCD40L, IL-8, MIP-1alpha, and MIP 1beta) could be used for assessing the quality of plasma or serum samples. PMID- 26808438 TI - ChREBP Regulates Itself and Metabolic Genes Implicated in Lipid Accumulation in beta-Cell Line. AB - Carbohydrate response element binding protein (ChREBP) is an important transcription factor that regulates a variety of glucose-responsive genes in hepatocytes. To date, only two natural isoforms, Chrebpalpha and Chrebpbeta, have been identified. Although ChREBP is known to be expressed in pancreatic beta cells, most of the glucose-responsive genes have never been verified as ChREBP targets in this organ. We aimed to explore the impact of ChREBP expression on regulating genes linked to accumulation of lipid droplets, a typical feature of beta-cell glucotoxicity. We assessed gene expression in 832/13 cells overexpressing constitutively active ChREBP (caChREBP), truncated ChREBP with nearly identical amino acid sequence to Chrebpbeta, or dominant negative ChREBP (dnChREBP). Among multiple ChREBP-controlled genes, ChREBP was sufficient and necessary for regulation of Eno1, Pklr, Mdh1, Me1, Pdha1, Acly, Acaca, Fasn, Elovl6, Gpd1, Cpt1a, Rgs16, Mid1ip1,Txnip, and Chrebpbeta. Expression of Chrebpalpha and Srebp1c were not changed by caChREBP or dnChREBP. We identified functional ChREBP binding sequences that were located on the promoters of Chrebpbeta and Rgs16. We also showed that Rgs16 overexpression lead to increased considerable amounts of lipids in 832/13 cells. This phenotype was accompanied by reduction of Cpt1a expression and slight induction of Fasn and Pklr gene in these cells. In summary, we conclude that Chrebpbeta modulates its own expression, not that of Chrebpalpha; it also regulates the expression of several metabolic genes in beta-cells without affecting SREBP-1c dependent regulation. We also demonstrate that Rgs16 is one of the ChREBP-controlled genes that potentiate accumulation of lipid droplets in beta-cells. PMID- 26808440 TI - Motivation and Barriers for Leisure-Time Physical Activity in Socioeconomically Disadvantaged Women. AB - INTRODUCTION: The aim of this study was to examine cross-sectional and longitudinal associations between motivation and barriers for physical activity, and physical activity behavior in women living in socioeconomic disadvantage. This study also examined whether weight control intentions moderate those associations. METHODS: Data from 1664 women aged 18-46 years was collected at baseline and three-year follow-up as part of the Resilience for Eating and Activity Despite Inequality study. In mail-based surveys, women reported sociodemographic and neighborhood environmental characteristics, intrinsic motivation, goals and perceived family barriers to be active, weight control intentions and leisure-time physical activity (assessed through the IPAQ-L). Linear regression models assessed the association of intrinsic motivation, goals and barriers with physical activity at baseline and follow-up, adjusting for environmental characteristics and also physical activity at baseline (for longitudinal analyses), and the moderating effects of weight control intentions were examined. RESULTS: Intrinsic motivation and, to a lesser extent, appearance and relaxation goals for being physically active were consistently associated with leisure-time physical activity at baseline and follow-up. Perceived family barriers, health, fitness, weight and stress relief goals were associated with leisure-time physical activity only at baseline. Moderated regression analyses revealed that weight control intentions significantly moderated the association between weight goals and leisure-time physical activity at baseline (beta = 0.538, 99% CI = 0.057, 0.990) and between intrinsic motivation and leisure-time physical activity at follow-up (beta = 0.666, 99% CI = 0.188, 1.145). For women actively trying to control their weight, intrinsic motivation was significantly associated with leisure-time physical activity at follow-up (beta = 0.184, 99% CI = 0.097, 0.313). CONCLUSIONS: Results suggest that, especially in women trying to control their weight, intrinsic motivation plays an important role in sustaining physical activity participation over time. Also, weight goals for being physically active seem to play a role regarding short-term physical activity participation in this particular population. Addressing these motivational features may be important when promoting physical activity participation in women living in socioeconomically disadvantaged neighborhoods. PMID- 26808442 TI - Bone matrix hypermineralization in prolyl-3 hydroxylase 1 deficient mice. AB - Lack of prolyl 3-hydroxylase 1 (P3H1) due to mutations in P3H1 results in severe forms of recessive osteogenesis imperfecta. In the present study, we investigated the bone tissue characteristics of P3H1 null mice. Histomorphometric analyses of cancellous bone in the proximal tibia and lumbar vertebra in 1-month and 3-month old mice demonstrated that P3H1 deficient mice had low trabecular bone volume and low mineral apposition rate, but normal osteoid maturation time and normal osteoblast and osteoclast surfaces. Quantitative backscattered electron imaging revealed that the bone mineralization density distribution was shifted towards higher values, indicating hypermineralization of bone matrix. It thus appears that P3H1 deficiency leads to decreased deposition of extracellular matrix by osteoblasts and increased incorporation of mineral into the matrix. PMID- 26808441 TI - Revisiting propranolol and PTSD: Memory erasure or extinction enhancement? AB - Posttraumatic stress disorder (PTSD) has been described as the only neuropsychiatric disorder with a known cause, yet effective behavioral and pharmacotherapies remain elusive for many afflicted individuals. PTSD is characterized by heightened noradrenergic signaling, as well as a resistance to extinction learning. Research aimed at promoting more effective treatment of PTSD has focused on memory erasure (disrupting reconsolidation) and/or enhancing extinction retention through pharmacological manipulations. Propranolol, a beta adrenoceptor antagonist, has received considerable attention for its therapeutic potential in PTSD, although its impact on patients is not always effective. In this review, we briefly examine the consequences of beta-noradrenergic manipulations on both reconsolidation and extinction learning in rodents and in humans. We suggest that propranolol is effective as a fear-reducing agent when paired with behavioral therapy soon after trauma when psychological stress is high, possibly preventing or dampening the later development of PTSD. In individuals who have already suffered from PTSD for a significant period of time, propranolol may be less effective at disrupting reconsolidation of strong fear memories. Also, when PTSD has already developed, chronic treatment with propranolol may be more effective than acute intervention, given that individuals with PTSD tend to experience long-term, elevated noradrenergic hyperarousal. PMID- 26808443 TI - Reactions of 2-Substituted Pyridines with Titanocenes and Zirconocenes: Coupling versus Dearomatisation. AB - Reactions of group 4 metallocene sources with 2-substituted pyridines were investigated to evaluate their coordination type between innocent and reductive dearomatisation as well as to probe the possibility for couplings. A dependence on the cyclopentadienyl ligands (Cp, Cp*), the metals (Ti, Zr), and the substrates (2-phenyl-, 2-acetyl-, and 2-iminopyridine) was observed. While 2 phenylpyridine is barely reactive, 2-acetylpyridine reacts vigorously with the Cp substituted complexes and selectively with their Cp* analogues. With 2 iminopyridine, in all cases selective reactions were observed. In the isolated [Cp2 Ti], [Cp2 Zr], and [Cp*2 Zr] compounds the substrate coordinates by its pyridyl ring and the unsaturated side-chain. Subsequently, the pyridine was dearomatised, which is most pronounced in the [Cp*2 Zr] compounds. Using [Cp*2 Ti] leads to the unexpected paramagnetic complexes [Cp*2 TiIII (N,O-acpy)] and [Cp*2 TiIII (N,N'-impy)]. This highlights the non-innocent character of the pyridyl substrates. PMID- 26808445 TI - Plant-Microbe Communication Enhances Auxin Biosynthesis by a Root-Associated Bacterium, Bacillus amyloliquefaciens SQR9. AB - Mechanisms by which beneficial rhizobacteria promote plant growth include tryptophan-dependent indole-3-acetic acid (IAA) synthesis. The abundance of tryptophan in the rhizosphere, however, may influence the level of benefit provided by IAA-producing rhizobacteria. This study examined the cucumber Bacillus amyloliquefaciens SQR9 system and found that SQR9, a bacterium previously shown to enhance the growth of cucumber, increased root secretion of tryptophan by three- to fourfold. Using a split-root system, SQR9 colonization of roots in one chamber not only increased tryptophan secretion from the noninoculated roots but also increased the expression of the cucumber tryptophan transport gene but not the anthranilate synthesis gene in those roots. The increased tryptophan in isolated rhizosphere exudates was sufficient to support increased IAA production by SQR9. Moreover, SQR9 colonization of roots in one chamber in the split-root system resulted in sufficient tryptophan production by the other roots to upregulate SQR9 IAA biosynthesis genes, including a 27-fold increase in the indole-3-acetonitrilase gene yhcX during subsequent colonization of those roots. Deletion of yhcX eliminated SQR9-mediated increases in root surface area, likely by reducing IAA-stimulated lateral root growth. This study demonstrates a chemical dialogue between B. amyloliquefaciens and cucumber in which this communication contributes to bacteria-mediated plant-growth enhancement. PMID- 26808444 TI - Conserved Patterns of Microbial Immune Escape: Pathogenic Microbes of Diverse Origin Target the Human Terminal Complement Inhibitor Vitronectin via a Single Common Motif. AB - Pathogenicity of many microbes relies on their capacity to resist innate immunity, and to survive and persist in an immunocompetent human host microbes have developed highly efficient and sophisticated complement evasion strategies. Here we show that different human pathogens including Gram-negative and Gram positive bacteria, as well as the fungal pathogen Candida albicans, acquire the human terminal complement regulator vitronectin to their surface. By using truncated vitronectin fragments we found that all analyzed microbial pathogens (n = 13) bound human vitronectin via the same C-terminal heparin-binding domain (amino acids 352-374). This specific interaction leaves the terminal complement complex (TCC) regulatory region of vitronectin accessible, allowing inhibition of C5b-7 membrane insertion and C9 polymerization. Vitronectin complexed with the various microbes and corresponding proteins was thus functionally active and inhibited complement-mediated C5b-9 deposition. Taken together, diverse microbial pathogens expressing different structurally unrelated vitronectin-binding molecules interact with host vitronectin via the same conserved region to allow versatile control of the host innate immune response. PMID- 26808446 TI - A Temperature-Independent Cold-Shock Protein Homolog Acts as a Virulence Factor in Xylella fastidiosa. AB - Xylella fastidiosa, causal agent of Pierce's disease (PD) of grapevine, is a fastidious organism that requires very specific conditions for replication and plant colonization. Cold temperatures reduce growth and survival of X. fastidiosa both in vitro and in planta. However, little is known regarding physiological responses of X. fastidiosa to temperature changes. Cold-shock proteins (CSP), a family of nucleic acid-binding proteins, act as chaperones facilitating translation at low temperatures. Bacterial genomes often encode multiple CSP, some of which are strongly induced following exposure to cold. Additionally, CSP contribute to the general stress response through mRNA stabilization and posttranscriptional regulation. A putative CSP homolog (Csp1) with RNA-binding activity was identified in X. fastidiosa Stag's Leap. The csp1 gene lacked the long 5' untranslated region characteristic of cold-inducible genes and was expressed in a temperature-independent manner. As compared with the wild type, a deletion mutant of csp1 (?csp1) had decreased survival rates following cold exposure and salt stress in vitro. The deletion mutant also was significantly less virulent in grapevine, as compared with the wild type, in the absence of cold stress. These results suggest an important function of X. fastidiosa Csp1 in response to cellular stress and during plant colonization. PMID- 26808447 TI - Aeroallergens, atopy and allergic rhinitis in the Middle East. AB - The literature on the nature and prevalence of indoor and/or outdoor aeroallergens, atopy and symptoms of rhinitis and asthma in the Middle East region (defined here as Bahrain, Egypt, Iran, Iraq, Israel, Jordan, Kuwait, Lebanon, Oman, Palestine, Qatar, Kingdom of Saudi Arabia - KSA, Syria, United Arab Emirates and Yemen) was reviewed. Although documentation was poor in all countries other than Iran and the KSA, a wide range of "global" and "local" aeroallergens (grass, weed and tree pollens, fungal spores, insect allergens, dander, and house dust mites) has been observed across the region. The prevalence of current self-reported or parent-reported symptoms of rhinitis ranged from 9% to 38%. Researchers have suggested that the high atopy rates and self-reported rhinitis rates are associated with an on-going shift towards a "western" lifestyle. PMID- 26808448 TI - Acute Hemorrhagic Edema of Infancy. AB - Acute Hemorrhagic Edema of Infancy is a small vessel leucocytoclastic vasculitis affecting young infants. It is characterized by large, target-like, macular to purpuric plaques predominantly affecting the face, ear lobes and extremities. Non pitting edema of the distal extremities and low-grade fever may also be present. Extra-cutaneous involvement is very rare. Although the lesions have a dramatic onset in a twenty-four to forty-eight hour period, usually the child has a non toxic appearance. In most cases there are no changes in laboratory parameters. The cutaneous biopsy reveals an inflammatory perivascular infiltrate. It is a benign and auto-limited disease, with complete resolution within two to three weeks leaving no sequelae in the majority of cases. No recurrences are described. We report a case of a 42-day old girl admitted at our hospital with Acute Hemorrhagic Edema of Infancy. PMID- 26808449 TI - Challenge-proven immediate type multiple local anesthetic hypersensitivity in a child. AB - Adverse reactions to local anesthetics (LA) are commonly reported in patients undergoing dental procedures and other minor surgical procedures. Most of these reactions, however, originate from psychosomatic, vasovagal or toxic conditions and are not immune-mediated. True immune-mediated reactions are considered extremely rare and are estimated to account for less than 1% of all adverse reactions to LA. On the other hand, almost all of the immune-mediated LA reactions that have been reported are related to adult patients. Here, however, we will present a pediatric case proven to be hypersensitive to two different amide-derivative LA's. PMID- 26808450 TI - A case of expressive-vocal amusia in a right-handed patient with left hemispheric cerebral infarction. AB - A 53-year-old right-handed woman had an extensive lesion in the left hemisphere due to an infarction caused by vasospasm secondary to subarachnoid bleeding. She exhibited persistent expressive-vocal amusia with no symptoms of aphasia. Evaluation of the patient's musical competence using the Montreal Battery for Evaluation of Amusia, rhythm reproduction tests, acoustic analysis of pitch upon singing familiar music, Japanese standard language tests, and other detailed clinical examinations revealed that her amusia was more dominantly related to pitch production. The intactness of her speech provided strong evidence that the right hemisphere played a major role in her linguistic processing. Data from functional magnetic resonance imaging while she was singing a familiar song, a scale, and reciting lyrics indicated that perilesional residual activation in the left hemisphere was associated with poor pitch production, while right hemispheric activation was involved in linguistic processing. The localization of infarction more anterior to the left Sylvian fissure might be related to the dominant deficits in expressive aspects of the singing of the patient. Compromised motor programming producing a single tone may have made a major contribution to her poor singing. Imperfect auditory feedback due to borderline perceptual ability or improper audio-motor associations might also have played a role. PMID- 26808451 TI - Reflection enhances creativity: Beneficial effects of idea evaluation on idea generation. AB - The present study aimed to explore the neural correlates underlying the effects of idea evaluation on idea generation in creative thinking. Participants were required to generate original uses of conventional objects (alternative uses task) during EEG recording. A reflection task (mentally evaluating the generated ideas) or a distraction task (object characteristics task) was inserted into the course of idea generation. Behavioral results revealed that participants generated ideas with higher originality after evaluating the generated ideas than after performing the distraction task. The EEG results revealed that idea evaluation was accompanied with upper alpha (10-13 Hz) synchronization, most prominent at frontal cortical sites. Moreover, upper alpha activity in frontal cortices during idea generation was enhanced after idea evaluation. These findings indicate that idea evaluation may elicit a state of heightened internal attention or top-down activity that facilitates efficient retrieval and integration of internal memory representations. PMID- 26808452 TI - The potential of imogolite nanotubes as (co-)photocatalysts: a linear-scaling density functional theory study. AB - We report a linear-scaling density functional theory (DFT) study of the structure, wall-polarization absolute band-alignment and optical absorption of several, recently synthesized, open-ended imogolite (Imo) nanotubes (NTs), namely single-walled (SW) aluminosilicate (AlSi), SW aluminogermanate (AlGe), SW methylated aluminosilicate (AlSi-Me), and double-walled (DW) AlGe NTs. Simulations with three different semi-local and dispersion-corrected DFT functionals reveal that the NT wall-polarization can be increased by nearly a factor of four going from SW-AlSi-Me to DW-AlGe. Absolute vacuum alignment of the NT electronic bands and comparison with those of rutile and anatase TiO2 suggest that the NTs may exhibit marked propensity to both photo-reduction and hole scavenging. Characterization of the NTs' band-separation and optical properties reveal the occurrence of (near-)UV inside-outside charge-transfer excitations, which may be effective for electron-hole separation and enhanced photocatalytic activity. Finally, the effects of the NTs' wall-polarization on the absolute alignment of electron and hole acceptor states of interacting water (H2O) molecules are quantified and discussed. PMID- 26808453 TI - HNF1 regulates critical processes in the human epididymis epithelium. AB - The luminal environment of the epididymis participates in sperm maturation and impacts male fertility. It is dependent on the coordinated expression of many genes encoding proteins with a role in epithelial transport. We identified cis regulatory elements for critical genes in epididymis function, by mapping open chromatin genome-wide in human epididymis epithelial (HEE) cells. Bioinformatic predictions of transcription factors binding to the regulatory elements suggested an important role for hepatocyte nuclear factor 1 (HNF1) in the transcriptional program of these cells. Chromatin immunoprecipitation and deep sequencing (ChIP seq) revealed HNF1 target genes in HEE cells. In parallel, the contribution of HNF1 to the transcriptome of HEE cells was determined by RNA-seq, following siRNA mediated depletion of both HNF1alpha and HNF1beta transcription factors. Repression of these factors caused differential expression of 1892 transcripts (902 were downregulated and 990 upregulated) in comparison to non-targeting siRNAs. Differentially expressed genes with HNF1 ChIP-seq peaks within 20 kb were subject to gene ontology process enrichment analysis. Among the most significant processes associated with down-regulated genes were epithelial transport of water, phosphate and bicarbonate, all critical processes in epididymis epithelial function. Measurements of intracellular pH (pHi) confirmed a role for HNF1 in regulating the epididymis luminal environment. PMID- 26808454 TI - Colorectal cancer outcomes and treatment patterns in patients too young for average-risk screening. AB - BACKGROUND: Although colorectal cancer (CRC) screening guidelines recommend initiating screening at age 50 years, the percentage of cancer cases in younger patients is increasing. To the authors' knowledge, the national treatment patterns and outcomes of these patients are largely unknown. METHODS: The current study was a population-based, retrospective cohort study of the nationally representative Surveillance, Epidemiology, and End Results registry for patients diagnosed with CRC from 1998 through 2011. Patients were categorized as being younger or older than the recommended screening age. Differences with regard to stage of disease at diagnosis, patterns of therapy, and disease-specific survival were compared between age groups using multinomial regression, multiple regression, Cox proportional hazards regression, and Weibull survival analysis. RESULTS: Of 258,024 patients with CRC, 37,847 (15%) were aged <50 years. Young patients were more likely to present with regional (relative risk ratio, 1.3; P<.001) or distant (relative risk ratio, 1.5; P<.001) disease. Patients with CRC with distant metastasis in the younger age group were more likely to receive surgical therapy for their primary tumor (adjusted probability: 72% vs 63%; P<.001), and radiotherapy also was more likely in younger patients with CRC (adjusted probability: 53% vs 48%; P<.001). Patients younger than the recommended screening age had better overall disease-specific survival (hazards ratio, 0.77; P<.001), despite a larger percentage of these individuals presenting with advanced disease. CONCLUSIONS: Patients with CRC diagnosed at age <50 years are more likely to present with advanced-stage disease. However, they receive more aggressive therapy and achieve longer disease-specific survival, despite the greater percentage of patients with advanced-stage disease. These findings suggest the need for improved risk assessment and screening decisions for younger adults. PMID- 26808455 TI - Atypical development of the central auditory system in young children with Autism spectrum disorder. AB - The P1m component of the auditory evoked magnetic field is the earliest cortical response associated with language acquisition. However, the growth curve of the P1m component is unknown in both typically developing (TD) and atypically developing children. The aim of this study is to clarify the developmental pattern of this component when evoked by binaural human voice stimulation using child-customized magnetoencephalography. A total of 35 young TD children (32-121 months of age) and 35 children with autism spectrum disorder (ASD) (38-111 months of age) participated in this study. This is the first report to demonstrate an inverted U-shaped growth curve for the P1m dipole intensity in the left hemisphere in TD children. In addition, our results revealed a more diversified age-related distribution of auditory brain responses in 3- to 9-year-old children with ASD. These results demonstrate the diversified growth curve of the P1m component in ASD during young childhood, which is a crucial period for first language acquisition. Autism Res 2016, 9: 1216-1226. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 26808456 TI - Polydopamine Wrapping Silicon Cross-linked with Polyacrylic Acid as High Performance Anode for Lithium-Ion Batteries. AB - A robust silicon electrode for lithium-ion battery has been developed via prepolymerizing dopamine on silicon particle surface and then chemical binding with poly(acrylic acid) (PAA). In this favorable electrode, silicon nanoparticles are covered by a thin layer of polydopamine (PD) through firm hydrogen bonds between phenolic hydroxyl and hydroxyl, while the elastic polymer layer reacts with PAA binder to form three-dimensional cross-linked binding system. The Si@PD/PAA electrode exhibits more stable cycle performance than conventional electrodes. In the case of thick electrode, a capacity of 3.69 mA h cm(-2) and fairly good rechargeability for 80 cycles can be achieved. PMID- 26808457 TI - Reactions of graphene supported Co3O4 nanocubes with lithium and magnesium studied by in situ transmission electron microscopy. AB - Reaction beyond intercalation and the utilization of metal ions beyond lithium ions are two promising approaches for developing the next generation of high capacity and low cost energy storage materials. Here, we use graphene supported Co3O4 nanocubes and study their reaction with lithium, magnesium and aluminum using in situ transmission electron microscopy. On lithiation, the Co3O4 nanocubes decompose to Co metal nanoparticles (2 to 3 nm) and embed in as-formed Li2O matrix; conversely, the CoO nanoparticles form on the Co site accompanying the decomposition of Li2O in the delithiation process. The lithiation process is dominated by surface diffusion of Li(+), and graphene sheets enhance the Li(+) diffusion. However, upon charge with magnesium, the Mg(2+) diffusion is sluggish, and there is no sign of conversion reaction between Mg and Co3O4 at room temperature. Instead, a thin film consisting of metal Mg nanoparticles is formed on the surface of graphene due to a process similar to metal plating. The Al(3+) diffusion is even more sluggish and no reaction between Al and Co3O4 is observed. These findings provide insights to tackle the reaction mechanism of multivalent ions with electrode materials. PMID- 26808458 TI - Interfacial electronic effects control the reaction selectivity of platinum catalysts. AB - Tuning the electronic structure of heterogeneous metal catalysts has emerged as an effective strategy to optimize their catalytic activities. By preparing ethylenediamine-coated ultrathin platinum nanowires as a model catalyst, here we demonstrate an interfacial electronic effect induced by simple organic modifications to control the selectivity of metal nanocatalysts during catalytic hydrogenation. This we apply to produce thermodynamically unfavourable but industrially important compounds, with ultrathin platinum nanowires exhibiting an unexpectedly high selectivity for the production of N-hydroxylanilines, through the partial hydrogenation of nitroaromatics. Mechanistic studies reveal that the electron donation from ethylenediamine makes the surface of platinum nanowires highly electron rich. During catalysis, such an interfacial electronic effect makes the catalytic surface favour the adsorption of electron-deficient reactants over electron-rich substrates (that is, N-hydroxylanilines), thus preventing full hydrogenation. More importantly, this interfacial electronic effect, achieved through simple organic modifications, may now be used for the optimization of commercial platinum catalysts. PMID- 26808459 TI - Programming curvature using origami tessellations. AB - Origami describes rules for creating folded structures from patterns on a flat sheet, but does not prescribe how patterns can be designed to fit target shapes. Here, starting from the simplest periodic origami pattern that yields one-degree of-freedom collapsible structures-we show that scale-independent elementary geometric constructions and constrained optimization algorithms can be used to determine spatially modulated patterns that yield approximations to given surfaces of constant or varying curvature. Paper models confirm the feasibility of our calculations. We also assess the difficulty of realizing these geometric structures by quantifying the energetic barrier that separates the metastable flat and folded states. Moreover, we characterize the trade-off between the accuracy to which the pattern conforms to the target surface, and the effort associated with creating finer folds. Our approach enables the tailoring of origami patterns to drape complex surfaces independent of absolute scale, as well as the quantification of the energetic and material cost of doing so. PMID- 26808460 TI - Colloidal metal oxide nanocrystal catalysis by sustained chemically driven ligand displacement. AB - Surface chemistry is a key enabler for colloidal nanocrystal applications. In this respect, metal oxide nanocrystals (NCs) stand out from other NCs as carboxylic acid ligands adsorb on their surface by dissociation to carboxylates and protons, the latter proving essential in electron transfer reactions. Here, we show that this binding motif sets the stage for chemically driven ligand displacement where the binding of amines or alcohols to HfO2 NCs is promoted by the conversion of a bound carboxylic acid into a non-coordinating amide or ester. Furthermore, the sustained ligand displacement, following the addition of excess carboxylic acid, provides a catalytic pathway for ester formation, whereas the addition of esters leads to NC-catalysed transesterification. Because sustained, chemically driven ligand displacement leaves the NCs-including their surface composition-unchanged and preserves colloidal stability, metal oxide nanocrystals are thus turned into effective nanocatalysts that bypass the tradeoff between colloidal stability and catalytic activity. PMID- 26808461 TI - Biomimetic 4D printing. AB - Shape-morphing systems can be found in many areas, including smart textiles, autonomous robotics, biomedical devices, drug delivery and tissue engineering. The natural analogues of such systems are exemplified by nastic plant motions, where a variety of organs such as tendrils, bracts, leaves and flowers respond to environmental stimuli (such as humidity, light or touch) by varying internal turgor, which leads to dynamic conformations governed by the tissue composition and microstructural anisotropy of cell walls. Inspired by these botanical systems, we printed composite hydrogel architectures that are encoded with localized, anisotropic swelling behaviour controlled by the alignment of cellulose fibrils along prescribed four-dimensional printing pathways. When combined with a minimal theoretical framework that allows us to solve the inverse problem of designing the alignment patterns for prescribed target shapes, we can programmably fabricate plant-inspired architectures that change shape on immersion in water, yielding complex three-dimensional morphologies. PMID- 26808462 TI - Successful Resuscitation: Novel Partnership between Paramedics and U.S. Coast Guard. AB - In this article, we present a notable case that illustrates a novel partnership between a United States Coast Guard small boat station and a civilian paramedic response unit. Patients who experience medical emergencies in remote environments are at particularly high risk for morbidity and mortality. For the most serious conditions, delayed contact with Advanced Life Support (ALS) has grave results. Typically, these circumstances involve small groups of individuals and cannot be easily predicted. The waters off the coasts of Maui, Hawaii, however, host millions of residents and visitors annually, with activities including swimming, snorkeling, diving, parasailing, and other types of ocean recreation. As a result, medical and rescue emergencies are not uncommon, many with poor outcomes. Prior to October of 2013, a Coast Guard response boat crew with limited medical training and equipment responded to most off shore cases. Since October 2013, a paramedic from Maui County EMS co-responds aboard the Coast Guard boat with a full complement of ALS equipment. This partnership has resulted in some significant improvements in patient outcome, and strengthened a collaborative emergency services system. The experience has also indicated the need for continued improvement in early activation and communication, as well as reinforcing the importance of primary prevention. PMID- 26808463 TI - Implementation of High-Order Multireference Coupled-Cluster Methods on Intel Many Integrated Core Architecture. AB - In this paper we discuss the implementation of multireference coupled-cluster formalism with singles, doubles, and noniterative triples (MRCCSD(T)), which is capable of taking advantage of the processing power of the Intel Xeon Phi coprocessor. We discuss the integration of two levels of parallelism underlying the MRCCSD(T) implementation with computational kernels designed to offload the computationally intensive parts of the MRCCSD(T) formalism to Intel Xeon Phi coprocessors. Special attention is given to the enhancement of the parallel performance by task reordering that has improved load balancing in the noniterative part of the MRCCSD(T) calculations. We also discuss aspects regarding efficient optimization and vectorization strategies. PMID- 26808464 TI - Intranasal topical estrogen in the management of epistaxis in hereditary hemorrhagic telangiectasia. AB - CONCLUSION: Application of topical estriol ointment is an effective treatment for hereditary hemorrhagic telangiectasia (HHT) epistaxis. OBJECTIVE: HHT is an autosomal-dominant disease characterized by epistaxis in more than 96% of patients. Management of this major symptom, epistaxis, has not been standardized. This study reports experience with topical application of estriol in patients with HHT. METHODS: Five patients with a confirmed diagnosis of HHT who first visited the hospital between 2012 and 2013 received 0.1% estriol ointment and were guided to apply the ointment twice daily to the anterior part of both nasal cavities. Severity of epistaxis was valued using epistaxis severity score (ESS) before and 3 months after initiating therapy. RESULTS: Five patients (three males, two females) received treatment. After the initiation of treatment, intensity and frequency of epistaxis became moderate in all patients. ESS decreased significantly from pre- to post-treatment (p = 0.043). No adverse events were recorded during follow-up. PMID- 26808465 TI - Quercetin is an effective inhibitor of quorum sensing, biofilm formation and virulence factors in Pseudomonas aeruginosa. AB - AIMS: The study aimed to perform a systematic investigation of the effects of quercetin on biofilm formation and virulence factors in Pseudomonas aeruginosa. METHODS AND RESULTS: The Ps. aeruginosa strain PAO1 was selected as the test strain. The results indicated that quercetin did not impact the growth of PAO1 as determined by MIC and growth curve analysis. However, this compound significantly inhibited (P < 0.05) biofilm formation and production of virulence factors including pyocyanin, protease and elastase at a lower concentration than those for most previously reported plant extracts and substances. Considering the central role of quorum sensing (QS) in the regulation of biofilm and virulence factor, we further detected the transcriptional changes associated with QS and found that the expression levels of lasI, lasR, rhlI and rhlR were significantly reduced (P < 0.05) by 34, 68, 57 and 50%, respectively, in response to 16 MUg ml( 1) quercetin. CONCLUSIONS: This study indicated that quercetin is an effective inhibitor of biofilm formation and virulence factors in Ps. aeruginosa. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to demonstrate that quercetin is an effective inhibitor of QS, biofilm formation and virulence factors in Ps. aeruginosa. Furthermore, quercetin might have potential in fighting biofilm-related infections. PMID- 26808466 TI - TGF-beta gene transfer and overexpression via rAAV vectors stimulates chondrogenic events in human bone marrow aspirates. AB - Genetic modification of marrow concentrates may provide convenient approaches to enhance the chondrogenic differentiation processes and improve the repair capacities in sites of cartilage defects following administration in the lesions. Here, we provided clinically adapted recombinant adeno-associated virus (rAAV) vectors to human bone marrow aspirates to promote the expression of the potent transforming growth factor beta (TGF-beta) as a means to regulate the biological and chondrogenic activities in the samples in vitro. Successful TGF-beta gene transfer and expression via rAAV was reached relative to control (lacZ) treatment (from 511.1 to 16.1 pg rhTGF-beta/mg total proteins after 21 days), allowing to durably enhance the levels of cell proliferation, matrix synthesis, and chondrogenic differentiation. Strikingly, in the conditions applied here, application of the candidate TGF-beta vector was also capable of reducing the hypertrophic and osteogenic differentiation processes in the aspirates, showing the potential benefits of using this particular vector to directly modify marrow concentrates to generate single-step, effective approaches that aim at improving articular cartilage repair in vivo. PMID- 26808468 TI - Long-Term Care Policy: Singapore's Experience. AB - Singapore, like many developed countries, is facing the challenge of a rapidly aging population and the increasing need to provide long-term care (LTC) services for elderly in the community. The Singapore government's philosophy on care for the elderly is that the family should be the first line of support, and it has relied on voluntary welfare organizations (VWOs) or charities for the bulk of LTC service provision. For LTC financing, it has emphasized the principles of co payment and targeting of state support to the low-income population through means tested government subsidies. It has also instituted ElderShield, a national severe disability insurance scheme. This paper discusses some of the challenges facing LTC policy in Singapore, particularly the presence of perverse financial incentives for hospitalization, the pitfalls of over-reliance on VWOs, and the challenges facing informal family caregivers. It discusses the role of private LTC insurance in LTC financing, bearing in mind demand- and supply-side failures that have plagued the private LTC insurance market. It suggests the need for more standardized needs assessment and portable LTC benefits, with reference to the Japanese Long-Term Care Insurance program, and also discusses the need to provide more support to informal family caregivers. PMID- 26808467 TI - LRRK2 G2019S transgenic mice display increased susceptibility to 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mediated neurotoxicity. AB - Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common causes of late onset autosomal dominant form of Parkinson disease (PD). Gain of kinase activity due to the substitution of Gly 2019 to Ser (G2019S) is the most common mutation in the kinase domain of LRRK2. Genetic predisposition and environmental toxins contribute to the susceptibility of neurodegeneration in PD. To identify whether the genetic mutations in LRRK2 increase the susceptibility to environmental toxins in PD models, we exposed transgenic mice expressing human G2019S mutant or wild type (WT) LRRK2 to the environmental toxin 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP treatment resulted in a greater loss of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta (SNpc) in LRRK2 G2019S transgenic mice compared to the LRRK2 WT overexpressing mice. Similarly loss of dopamine levels were greater in the striatum of LRRK2 G2019S mice when compared to the LRRK2 WT mice when both were treated with MPTP. This study suggests a likely interaction between genetic and environmental risk factors in the PD pathogenesis and that the G2019S mutation in LRRK2 increases the susceptibility of dopamine neurons to PD-causing toxins. PMID- 26808469 TI - Technology assessment of innovative medical devices in Europe. PMID- 26808470 TI - Synthesis, Activity, and Docking Study of Novel Phenylthiazole-Carboxamido Acid Derivatives as FFA2 Agonists. AB - Free fatty acid receptor 2 (FFA2), also known as GPR43, is activated by short chain fatty acids (SCFAs) that are mainly produced by the gut microbiota through the fermentation of undigested carbohydrates and dietary fibers. FFA2 currently appears to be a potential target in the management of obesity, diabetes, inflammatory diseases, and cancer. In the study, a series of novel phenylthiazole carboxamido acid derivatives has been synthesized and evaluated as potential orthosteric FFA2 ligands for the study of structure-activity relationships. Compound 6e was found to exhibit the twofold potent agonistic activity in the stable hFFA2-transfected CHO-K1 cells (EC50 = 23.1 MUm) as that of positive control propionate (EC50 = 43.3 MUm). We also reported the results of mutagenesis studies based on the crystal structure of hFFA1 bound to TAK-875 at 2.3 A resolution to identify important residues for orthosteric agonist 6e inducing FFA2 activation. PMID- 26808471 TI - Extracorporeal shock waves modulate myofibroblast differentiation of adipose derived stem cells. AB - Mesenchymal stem cells are precursors of myofibroblasts, cells deeply involved in promoting tissue repair and regeneration. However, since myofibroblast persistence is associated with the development of tissue fibrosis, the use of tools that can modulate stem cell differentiation toward myofibroblasts is central. Extracorporeal shock waves are transient short-term acoustic pulses first employed to treat urinary stones. They are a leading choice in the treatment of several orthopedic diseases and, notably, they have been reported as an effective treatment for patients with fibrotic sequels from burn scars. Based on these considerations, the aim of this study is to define the role of shock waves in modulating the differentiation of human adipose-derived stem cells toward myofibroblasts. Shock waves inhibit the development of a myofibroblast phenotype; they down-regulate the expression of the myofibroblast marker alpha smooth muscle actin and the extracellular matrix protein type I collagen. Functionally, stem cells acquire a more fibroblast-like profile characterized by a low contractility and a high migratory ability. Shock wave treatment reduces the expression of integrin alpha 11, a major collagen receptor in fibroblastic cells, involved in myofibroblast differentiation. Mechanistically, the resistance of integrin alpha 11-overexpressing cells to shock waves in terms of alpha smooth muscle actin expression and cell migration and contraction suggests also a role of this integrin in the translation of shock wave signal into stem cell responses. In conclusion, this in vitro study shows that stem cell differentiation toward myofibroblasts can be controlled by shock waves and, consequently, sustains their use as a therapeutic approach in reducing the risk of skin and tissue fibrosis. PMID- 26808472 TI - Heat effects on drug delivery across human skin. AB - INTRODUCTION: Exposure to heat can impact the clinical efficacy and/or safety of transdermal and topical drug products. Understanding these heat effects and designing meaningful in vitro and in vivo methods to study them are of significant value to the development and evaluation of drug products dosed to the skin. AREAS COVERED: This review provides an overview of the underlying mechanisms and the observed effects of heat on the skin and on transdermal/topical drug delivery, thermoregulation and heat tolerability. The designs of several in vitro and in vivo heat effect studies and their results are reviewed. EXPERT OPINION: There is substantial evidence that elevated temperature can increase transdermal/topical drug delivery. However, in vitro and in vivo methods reported in the literature to study heat effects of transdermal/topical drug products have utilized inconsistent study conditions, and in vitro models require better characterization. Appropriate study designs and controls remain to be identified, and further research is warranted to evaluate in vitro-in vivo correlations and the ability of in vitro models to predict in vivo effects. The physicochemical and pharmacological properties of the drug(s) and the drug product, as well as dermal clearance and heat gradients may require careful consideration. PMID- 26808473 TI - Long-term rebleeding risk following endoscopic therapy of small-bowel vascular lesions with device-assisted enteroscopy. AB - BACKGROUND AND AIMS: The effectiveness of endoscopic therapy of small-bowel vascular lesions (SBVL) remains unclear as recent studies report high recurrence rates after 2 years of follow-up. This study aimed to evaluate the long-term rebleeding risk after endoscopic therapy of SBVL and to identify predictive factors of rebleeding. METHODS: This was a retrospective single-center series of patients with SBVL treated endoscopically between July 2007 and February 2015. Relevant data from patient files, capsule endoscopies, and enteroscopy reports were retrieved. The primary endpoint was long-term rebleeding and the secondary endpoints were risk factors for rebleeding and transfusion requirements. RESULTS: Thirty-five patients were included. Capsule endoscopies indicated angioectasias in 74.3% and blood in the remaining; angioectasias were found in 97.1% of enteroscopies. Rebleeding occurred in 40% of patients during a median follow-up of 23 months (interquartile range 9-43). The rebleeding rate at 1, 2, 3, 4, and 5 years was 32.7, 38.3, 46.0, 53.7, and 63.0%, respectively. Only the presence of high-risk comorbidities (aortic valve stenosis, chronic renal or liver disease, or Osler-Weber-Rendu syndrome) was associated with higher rebleeding (P=0.006) in the univariate and multivariate analyses, being 51.3%/67.6% at 1/3 years, compared with 6.7%/22.2% in patients without any of these comorbidities. Transfusion requirements decreased to 6.3 (0.0-6.0) packed red blood cells units the year after endoscopic therapy compared with 11.5 (2.0-17.0) in the previous year (P=0.002). CONCLUSION: More than half of the patients had rebleeding after 5 years of follow-up, although transfusion requirements decreased. Patients with high-risk comorbidities are more likely to rebleed. PMID- 26808474 TI - Effect of Metformin Treatment on Lipoprotein Subfractions in Non-Diabetic Patients with Acute Myocardial Infarction: A Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) Trial. AB - OBJECTIVE: Metformin affects low density lipoprotein (LDL) and high density (HDL) subfractions in the context of impaired glucose tolerance, but its effects in the setting of acute myocardial infarction (MI) are unknown. We determined whether metformin administration affects lipoprotein subfractions 4 months after ST segment elevation MI (STEMI). Second, we assessed associations of lipoprotein subfractions with left ventricular ejection fraction (LVEF) and infarct size 4 months after STEMI. METHODS: 371 participants without known diabetes participating in the GIPS-III trial, a placebo controlled, double-blind randomized trial studying the effect of metformin (500 mg bid) during 4 months after primary percutaneous coronary intervention for STEMI were included of whom 317 completed follow-up (clinicaltrial.gov Identifier: NCT01217307). Lipoprotein subfractions were measured using nuclear magnetic resonance spectroscopy at presentation, 24 hours and 4 months after STEMI. (Apo)lipoprotein measures were obtained during acute STEMI and 4 months post-STEMI. LVEF and infarct size were measured by cardiac magnetic resonance imaging. RESULTS: Metformin treatment slightly decreased LDL cholesterol levels (adjusted P = 0.01), whereas apoB remained unchanged. Large LDL particles and LDL size were also decreased after metformin treatment (adjusted P<0.001). After adjustment for covariates, increased small HDL particles at 24 hours after STEMI predicted higher LVEF (P = 0.005). In addition, increased medium-sized VLDL particles at the same time point predicted a smaller infarct size (P<0.001). CONCLUSION: LDL cholesterol and large LDL particles were decreased during 4 months treatment with metformin started early after MI. Higher small HDL and medium VLDL particle concentrations are associated with favorable LVEF and infarct size. PMID- 26808475 TI - Asexual Reproduction Does Not Apparently Increase the Rate of Chromosomal Evolution: Karyotype Stability in Diploid and Triploid Clonal Hybrid Fish (Cobitis, Cypriniformes, Teleostei). AB - Interspecific hybridization, polyploidization and transitions from sexuality to asexuality considerably affect organismal genomes. Especially the last mentioned process has been assumed to play a significant role in the initiation of chromosomal rearrangements, causing increased rates of karyotype evolution. We used cytogenetic analysis and molecular dating of cladogenetic events to compare the rate of changes of chromosome morphology and karyotype in asexually and sexually reproducing counterparts in European spined loach fish (Cobitis). We studied metaphases of three sexually reproducing species and their diploid and polyploid hybrid clones of different age of origin. The material includes artificial F1 hybrid strains, representatives of lineage originated in Holocene epoch, and also individuals of an oldest known age to date (roughly 0.37 MYA). Thereafter we applied GISH technique as a marker to differentiate parental chromosomal sets in hybrids. Although the sexual species accumulated remarkable chromosomal rearrangements after their speciation, we observed no differences in chromosome numbers and/or morphology among karyotypes of asexual hybrids. These hybrids possess chromosome sets originating from respective parental species with no cytogenetically detectable recombinations, suggesting their integrity even in a long term. The switch to asexual reproduction thus did not provoke any significant acceleration of the rate of chromosomal evolution in Cobitis. Asexual animals described in other case studies reproduce ameiotically, while Cobitis hybrids described here produce eggs likely through modified meiosis. Therefore, our findings indicate that the effect of asexuality on the rate of chromosomal change may be context-dependent rather than universal and related to particular type of asexual reproduction. PMID- 26808476 TI - Brugia malayi Antigen (BmA) Inhibits HIV-1 Trans-Infection but Neither BmA nor ES 62 Alter HIV-1 Infectivity of DC Induced CD4+ Th-Cells. AB - One of the hallmarks of HIV-1 disease is the association of heightened CD4+ T cell activation with HIV-1 replication. Parasitic helminths including filarial nematodes have evolved numerous and complex mechanisms to skew, dampen and evade human immune responses suggesting that HIV-1 infection may be modulated in co infected individuals. Here we studied the effects of two filarial nematode products, adult worm antigen from Brugia malayi (BmA) and excretory-secretory product 62 (ES-62) from Acanthocheilonema viteae on HIV-1 infection in vitro. Neither BmA nor ES-62 influenced HIV-1 replication in CD4+ enriched T-cells, with either a CCR5- or CXCR4-using virus. BmA, but not ES-62, had the capacity to bind the C-type lectin dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) thereby inhibiting HIV-1 trans-infection of CD4+ enriched T-cells. As for their effect on DCs, neither BmA nor ES-62 could enhance or inhibit DC maturation as determined by CD83, CD86 and HLA-DR expression, or the production of IL-6, IL-10, IL-12 and TNF-alpha. As expected, due to the unaltered DC phenotype, no differences were found in CD4+ T helper (Th) cell phenotypes induced by DCs treated with either BmA or ES-62. Moreover, the HIV-1 susceptibility of the Th-cell populations induced by BmA or ES-62 exposed DCs was unaffected for both CCR5- and CXCR4-using HIV-1 viruses. In conclusion, although BmA has the potential capacity to interfere with HIV-1 transmission or initial viral dissemination through preventing the virus from interacting with DCs, no differences in the Th-cell polarizing capacity of DCs exposed to BmA or ES-62 were observed. Neither antigenic source demonstrated beneficial or detrimental effects on the HIV-1 susceptibility of CD4+ Th-cells induced by exposed DCs. PMID- 26808477 TI - Effect of Glucuronidation on the Potential of Kaempferol to Inhibit Serine/Threonine Protein Kinases. AB - To study the effect of metabolic conjugation of flavonoids on the potential to inhibit protein kinase activity, the inhibitory effects of the dietary flavonol kaempferol and its major plasma conjugate kaempferol-3-O-glucuronide on protein kinases were studied. To this end, the inhibition of the phosphorylation activity of recombinant protein kinase A (PKA) and of cell lysate from the hepatocellular carcinoma cell line HepG2 on 141 putative serine/threonine phosphorylation sites derived from human proteins was assessed. Glucuronidation reduced the inhibitory potency of kaempferol on the phosphorylation activity of PKA and HepG2 lysate on average about 16 and 3.5 times, respectively, but did not appear to affect the target selectivity for kinases present in the lysate. The data demonstrate that, upon glucuronidation, kaempferol retains part of its intrinsic kinase inhibition potential, which implies that K3G does not necessarily need to be deconjugated to the aglycone for a potential inhibitory effect on protein kinases. PMID- 26808478 TI - HIV-1 Integrase Strand Transfer Inhibitors with Reduced Susceptibility to Drug Resistant Mutant Integrases. AB - HIV integrase (IN) strand transfer inhibitors (INSTIs) are among the newest anti AIDS drugs; however, mutant forms of IN can confer resistance. We developed noncytotoxic naphthyridine-containing INSTIs that retain low nanomolar IC50 values against HIV-1 variants harboring all of the major INSTI-resistant mutations. We found by analyzing crystal structures of inhibitors bound to the IN from the prototype foamy virus (PFV) that the most successful inhibitors show striking mimicry of the bound viral DNA prior to 3'-processing and the bound host DNA prior to strand transfer. Using this concept of "bi-substrate mimicry," we developed a new broadly effective inhibitor that not only mimics aspects of both the bound target and viral DNA but also more completely fills the space they would normally occupy. Maximizing shape complementarity and recapitulating structural components encompassing both of the IN DNA substrates could serve as a guiding principle for the development of new INSTIs. PMID- 26808479 TI - Standardizing the influenza neuraminidase inhibition assay among United States public health laboratories conducting virological surveillance. AB - BACKGROUND: Monitoring influenza virus susceptibility to neuraminidase (NA) inhibitors (NAIs) is vital for detecting drug-resistant variants, and is primarily assessed using NA inhibition (NI) assays, supplemented by NA sequence analysis. However, differences in NI testing methodologies between surveillance laboratories results in variability of 50% inhibitory concentration (IC50) values, which impacts data sharing, reporting and interpretation. In 2011, the Centers for Disease Control and Prevention (CDC), in collaboration with the Association for Public Health Laboratories (APHL) spearheaded efforts to standardize fluorescence-based NI assay testing in the United States (U.S.), with the goal of achieving consistency of IC50 data. METHODS: For the standardization process, three participating state public health laboratories (PHLs), designated as National Surveillance Reference Centers for Influenza (NSRC-Is), assessed the NAI susceptibility of the 2011-12 CDC reference virus panel using stepwise procedures, with support from the CDC reference laboratory. Next, the NSRC-Is assessed the NAI susceptibility of season 2011-12 U.S. influenza surveillance isolates (n = 940), with a large subset (n = 742) tested in parallel by CDC. Subsequently, U.S. influenza surveillance isolates (n = 9629) circulating during the next three influenza seasons (2012-15), were independently tested by the three NSRC-Is (n = 7331) and CDC (n = 2298). RESULTS: The NI assay IC50s generated by respective NSRC-Is using viruses and drugs prepared by CDC were similar to those obtained with viruses and drugs prepared in-house, and were uniform between laboratories. IC50s for U.S. surveillance isolates tested during four consecutive influenza seasons (2011-15) were consistent from season to season, within and between laboratories. CONCLUSION: These results show that the NI assay is robust enough to be standardized, marking the first time IC50 data have been normalized across multiple laboratories, and used for U.S. national NAI susceptibility surveillance. PMID- 26808480 TI - Interleukin-6 is a negative regulator of hepatic glucose production in the isolated rat liver. AB - The mechanism underlying the increased rate of endogenous glucose production from the liver during exercise remains unknown. The cytokine interleukin-6 (IL-6) is known to be released during exercise and is thought that either IL-6 directly or via a "contraction factor" stimulates the release of stored glucose from the liver. Here we show that IL-6 does not directly increase hepatic glucose output (HGO). Moreover, IL-6 infused at the same time as glucagon caused a significant reduction in HGO. IL-6 infused with epinephrine caused no synergenic increase in HGO. To test if an unknown "contraction factor" was needed along with IL-6 to increase HGO, we used human fasted and exercised plasma perfused with or without IL-6 in our isolated liver system. We found that exercised plasma increased HGO, as expected, but when infused with IL-6, reductions in HGO were found. Our results provide evidence that IL-6 works as a negative regulator of HGO. PMID- 26808481 TI - Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease. AB - BACKGROUND: Cynomolgus macaques (Macaca fascicularis) represent a feasible model for research on Chagas disease since natural T. cruzi infection in these primates leads to clinical outcomes similar to those observed in humans. However, it is still unknown whether these clinical similarities are accompanied by equivalent immunological characteristics in the two species. We have performed a detailed immunophenotypic analysis of circulating leukocytes together with systems biology approaches from 15 cynomolgus macaques naturally infected with T. cruzi (CH) presenting the chronic phase of Chagas disease to identify biomarkers that might be useful for clinical investigations. METHODS AND FINDINGS: Our data established that CH displayed increased expression of CD32+ and CD56+ in monocytes and enhanced frequency of NK Granzyme A+ cells as compared to non-infected controls (NI). Moreover, higher expression of CD54 and HLA-DR by T-cells, especially within the CD8+ subset, was the hallmark of CH. A high level of expression of Granzyme A and Perforin underscored the enhanced cytotoxicity-linked pattern of CD8+ T-lymphocytes from CH. Increased frequency of B-cells with up-regulated expression of Fc-gammaRII was also observed in CH. Complex and imbricate biomarker networks demonstrated that CH showed a shift towards cross-talk among cells of the adaptive immune system. Systems biology analysis further established monocytes and NK-cell phenotypes and the T-cell activation status, along with the Granzyme A expression by CD8+ T-cells, as the most reliable biomarkers of potential use for clinical applications. CONCLUSIONS: Altogether, these findings demonstrated that the similarities in phenotypic features of circulating leukocytes observed in cynomolgus macaques and humans infected with T. cruzi further supports the use of these monkeys in preclinical toxicology and pharmacology studies applied to development and testing of new drugs for Chagas disease. PMID- 26808482 TI - Sitting Time and Obesity or Abdominal Obesity in Older South Koreans: Korean National Health and Nutrition Examination Survey 2013. AB - We examined relationships between sitting time and obesity or abdominal obesity according to sex and socioeconomic status in elderly people. We analyzed data from the Korean National Health and Nutrition Examination Survey 2013, and 1565 participants were included in the study. Multivariate logistic regression analysis was used to examine relationships between sitting time and obesity or abdominal obesity according to sex and socioeconomic status. Sitting time was positively correlated with body mass index in men and women and waist circumference in men. When considering socioeconomic factors, men who sat for 5 hours or longer and fell within the lowest income were more likely to have obesity and abdominal obesity relative to men who sat for 5 hours or shorter and earned higher incomes (odds ratio [95% confidence interval] = 1.80 [1.14-2.84] and 1.63 [1.02-2.61] respectively), and women who sat for 5 hours or longer and fell within the lowest educational level were more likely to have obesity relative to women who sat for 5 hours or less and were educated to a higher level (1.24 [1.01-1.85]). Strategies to reduce sedentary behavior would help to prevent obesity in older men who earn low incomes and women with lower levels of educational attainment. PMID- 26808483 TI - P-Type Polar Transition of Chemically Doped Multilayer MoS2 Transistor. AB - A high-performance multilayer MoS2 p-type field-effect transistor is realized via controllable chemical doping, which shows an excellent on/off ratio of 10(9) and a maximum hole mobility of 132 cm(2) V(-1) s(-1) at 133 K. The developed technique will enable 2D materials to be used for future high-efficiency and low power semiconductor device applications. PMID- 26808484 TI - Role of Electrostatic Interactions on the Transport of Druglike Molecules in Hydrogel-Based Articular Cartilage Mimics: Implications for Drug Delivery. AB - In the field of drug delivery to the articular cartilage, it is advantageous to apply artificial tissue models as surrogates of cartilage for investigating drug transport and release properties. In this study, artificial cartilage models consisting of 0.5% (w/v) agarose gel containing 0.5% (w/v) chondroitin sulfate or 0.5% (w/v) hyaluronic acid were developed, and their rheological and morphological properties were characterized. UV imaging was utilized to quantify the transport properties of the following four model compounds in the agarose gel and in the developed artificial cartilage models: H-Ala-beta-naphthylamide, H-Lys Lys-beta-naphthylamide, lysozyme, and alpha-lactalbumin. The obtained results showed that the incorporation of the polyelectrolytes chondroitin sulfate or hyaluronic acid into agarose gel induced a significant reduction in the apparent diffusivities of the cationic model compounds as compared to the pure agarose gel. The decrease in apparent diffusivity of the cationic compounds was not caused by a change in the gel structure since a similar reduction in apparent diffusivity was not observed for the net negatively charged protein alpha lactalbumin. The apparent diffusivity of the cationic compounds in the negatively charged hydrogels was highly dependent on the ionic strength, pointing out the importance of electrostatic interactions between the diffusant and the polyelectrolytes. Solution based affinity studies between the model compounds and the two investigated polyelectrolytes further confirmed the electrostatic nature of their interactions. The results obtained from the UV imaging diffusion studies are important for understanding the effect of drug physicochemical properties on the transport in articular cartilage. The extracted information may be useful in the development of hydrogels for in vitro release testing having features resembling the articular cartilage. PMID- 26808485 TI - Street network measures and adults' walking for transport: Application of space syntax. AB - The street network underpins the walkability of local neighborhoods. We examined whether two street network measures (intersection density and street integration from space syntax) were independently associated with walking for transport (WT); and, to what extent the relationship of street integration with WT may be explained by the presence of destinations. In 2003-2004, adults living in Adelaide, Australia (n=2544) reported their past-week WT frequency and perceived distances to 16 destination types. Marginal models via generalized estimating equations tested mediation effects. Both intersection density and street integration were significantly associated with WT, after adjusting for each other. Perceived destination availability explained 42% of the association of street integration with WT; this may be because of an association between street integration and local destination availability - an important element of neighborhood walkability. The use of space syntax concepts and methods has the potential to provide novel insights into built-environment influences on walking. PMID- 26808486 TI - Non-coding RNA profiling of the developing murine lens. AB - Non-coding RNAs (ncRNAs) are emerging as an important player in the regulation of genome integrity and gene expression, and they have been implicated in the pathogenesis of many diseases. The aim of the present study is to identify the repertoire of ncRNAs expressed in the developing mouse lens. We previously reported the mouse lens transcriptome, including mRNA and microRNA (miRNA) profiling at two embryonic (E15 and E18) and four postnatal (P0, P3, P6, and P9) time points. We analyzed the data from small RNA-Seq and mRNA-Seq libraries to investigate the ncRNA profile. Our analysis revealed expression of 12 different classes of ncRNA in the murine lens at six developmental time points. Annotation of small RNA data showed expression of 1,756 antisense ncRNA (asncRNA) in the mouse lens transcriptome. Likewise, we identified 82 P-element-induced wimpy testis (PIWI)-interacting RNA (piRNA), 345 transfer RNA (tRNA), 12 small nuclear RNA (snRNA), 167 small nucleolar RNA (snoRNA), 19 small Cajal body-specific RNA (scaRNA), six ribosomal RNA (rRNA), 18 tRNA-like structures, one MALAT1 associated small cytoplasmic RNA (mascRNA), one Vault RNA (vtRNA), and one Y RNA expressed in the developing mouse lens. In parallel, bioinformatic investigation of mRNA-Seq data identified expression of 1,952 long intergenic ncRNA (lincRNA) in the developing mouse lens. In conclusion, we report a comprehensive ncRNA profile in the murine lens at six developmental time points. To the best of our knowledge, this is first report investigating different classes of ncRNAs in the developing mouse lens and will be monumental in elucidating processes essential for the development of the ocular lens and the maintenance of its transparency. PMID- 26808488 TI - Quercetin glycosides and chlorogenic acid in highbush blueberry leaf decoction prevent cataractogenesis in vivo and in vitro: Investigation of the effect on calpains, antioxidant and metal chelating properties. AB - The present study investigates whether highbush blueberry leaf polyphenols prevent cataractogenesis and the underlying mechanisms. Chlorogenic acid, quercetin, rutin, isoquercetin and hyperoside were quantified in Vaccinium corymbosum leaf decoction (BBL) using HPLC-DAD. Wistar rats were injected subcutaneously with 20 MUmol selenite (Na2SeO3)/kg body weight on postnatal (PN) day 10 (Se, n = 8-10/group) only or also intraperitoneally with 100 mg dry BBL/kg body weight on PN days 11 and 12 (SeBBL group, n = 10). Control group received only normal saline (C). Cataract evaluation revealed that BBL significantly prevented lens opacification. It, also, protected lens from selenite oxidative attack and prevented calpain activation, as well as protein loss and aggregation. In vitro studies showed that quercetin attenuated porcine lens turbidity caused by [Formula: see text] or Ca(2+) and interacted efficiently with those ions according to UV-Vis titration experiments. Finally, rutin, isoquercetin and hyperoside moderately inhibited pure human MU-calpain. Conclusively, blueberry leaf extract, a rich source of bioactive polyphenols, prevents cataractogenesis by their strong antioxidant, chelating properties and through direct/indirect inhibition of lens calpains. PMID- 26808489 TI - Peer Support Training Improved the Glycemic Control, Insulin Management, and Diabetic Behaviors of Patients with Type 2 Diabetes in Rural Communities of Central China: A Randomized Controlled Trial. AB - BACKGROUND: The efficacy of peer support in Chinese diabetes patients is still uncertain. The purpose of this study was to observe the effects of a peer support program on the outcomes of patients with type 2 diabetes who received community based insulin therapy in rural communities of central China. MATERIAL/METHODS: Two hundred and eight eligible patients with type 2 diabetes were randomly assigned into the traditional training group (control group, n=111) and peer support intervention group (peer group, n=97) between June 2013 and January 2014 in 2 rural communities of Jingzhou area, China. Both groups received 3-month traditional training, followed by another 4-month traditional training or peer support training, respectively. At baseline and 7 months after treatment, the blood glycemic level was evaluated by biochemical detection. Capacities of self management and knowledge related to insulin usage were assessed by questionnaire survey. RESULTS: Ninety-seven and ninety patients completed this study in the control group and peer group, respectively. There was no significant difference in age, gender, diabetes duration, insulin usage time, and complications between the 2 groups at baseline (P>0.05). Compared with the control group, peer group patients achieved a more significant decrease in blood glycosylated hemoglobin levels (P<0.05), increase in knowledge related to insulin usage, and increase of diabetes self-management ability (P<0.05). CONCLUSIONS: Peer support intervention effectively improves outcomes of patients with type 2 diabetes in rural communities of central China. PMID- 26808487 TI - Seasonal and post-trauma remodeling in cone-dominant ground squirrel retina. AB - With a photoreceptor mosaic containing ~85% cones, the ground squirrel is one of the richest known mammalian sources of these important retinal cells. It also has a visual ecology much like the human's. While the ground squirrel retina is understandably prominent in the cone biochemistry, physiology, and circuitry literature, far less is known about the remodeling potential of its retinal pigment epithelium, neurons, macroglia, or microglia. This review aims to summarize the data from ground squirrel retina to this point in time, and to relate them to data from other brain areas where appropriate. We begin with a survey of the ground squirrel visual system, making comparisons with traditional rodent models and with human. Because this animal's status as a hibernator often goes unnoticed in the vision literature, we then present a brief primer on hibernation biology. Next we review what is known about ground squirrel retinal remodeling concurrent with deep torpor and with rapid recovery upon re-warming. Notable here is rapidly-reversible, temperature-dependent structural plasticity of cone ribbon synapses, as well as pre- and post-synaptic plasticity throughout diverse brain regions. It is not yet clear if retinal cell types other than cones engage in torpor-associated synaptic remodeling. We end with the small but intriguing literature on the ground squirrel retina's remodeling responses to insult by retinal detachment. Notable for widespread loss of (cone) photoreceptors, there is surprisingly little remodeling of the RPE or Muller cells. Microglial activation appears minimal, and remodeling of surviving second- and third-order neurons seems absent, but both require further study. In contrast, traumatic brain injury in the ground squirrel elicits typical macroglial and microglial responses. Overall, the data to date strongly suggest a heretofore unrecognized, natural checkpoint between retinal deafferentiation and RPE and Muller cell remodeling events. As we continue to discover them, the unique ways by which ground squirrel retina responds to hibernation or injury may be adaptable to therapeutic use. PMID- 26808491 TI - Lower facial reanimation techniques following cancer resection and free flap reconstruction. AB - OBJECTIVES/HYPOTHESIS: Evaluate outcomes of the standard static sling and orthodromic temporalis tendon transfer reanimation for facial nerve paralysis. STUDY DESIGN: Retrospective case series at a tertiary care hospital of head and neck cancer patients with facial nerve palsy secondary to malignancy or resection. METHODS: From 2004 to 2014, patients undergoing resection of malignancy that involved facial nerve palsy requiring facial reanimation were identified. All procedures were performed by the senior author (e.l.r.). Demographics, methods, revision rates, combination with other procedures, and complications were evaluated. RESULTS: A total of 77 patients underwent 92 procedures, with two patients requiring more than one revision, for a total of 20 revisions. Average time to revision was 9 months. Age, sex, race, side of repair, paralysis prior to procedure, sling type or method, timing of procedure, and radiation therapy were not significantly different between those requiring revision and those who did not. There was no difference in complications between patients who received radiation and those who did not (P = .5), nor between static versus orthodromic temporalis muscle transfer (P = .5). Complication rate was low at 5.4%. CONCLUSIONS: Sling procedures can be successfully performed in patients with facial nerve palsy secondary to cancer resection with radiation therapy, with a low revision rate and few complications. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:1990-1994, 2016. PMID- 26808490 TI - The Association of Gum Bleeding with Respiratory Health in a Population Based Study from Northern Europe. AB - BACKGROUND: There is little knowledge about how oral and respiratory health is interrelated even though the mucosa of the oral cavity and airways constitutes a continuum and the exposures to these are partly similar. AIMS: To investigate whether gum bleeding is related to asthma, respiratory symptoms and self-reported COPD. METHODS: A postal questionnaire including questions about respiratory and oral health was sent to general population samples in seven Northern European centres. In 13,409 responders, gum bleeding when brushing teeth was reported always/often by 4% and sometimes by 20%. Logistic regressions accounted for age, smoking, educational level, centre and gender. Effects of BMI, cardio-metabolic diseases, early life factors, gastro-oesophageal reflux, dental hygiene, nasal congestion, and asthma medication were addressed. RESULTS: Gum bleeding always/often was significantly associated with >= 3 asthma symptoms (OR 2.58, 95% CI 2.10-3.18), asthma (1.62 [1.23-2.14]) and self-reported COPD (2.02 [1.28 3.18]). There was a dose-response relationship between respiratory outcomes and gum bleeding frequency (>= 3 symptoms: gum bleeding sometimes 1.42 [1.25-1.60], often/always 2.58 [2.10-3.18]), and there was no heterogeneity between centres (p(heterogeneity) = 0.49). None of the investigated risk factors explained the associations. The observed associations were significantly stronger among current smokers (p(interaction) = 0.004). CONCLUSIONS: A consistent link between gum bleeding and obstructive airways disease was observed, not explained by common risk factors or metabolic factors. We speculate that oral pathogens might have unfavourable impact on the airways, and that the direct continuity of the mucosa of the oral cavity and the airways reflects a pathway that might provide novel opportunities for interventions. PMID- 26808492 TI - The Incidence, Clinical Outcomes, and Risk Factors of Thrombocytopenia in Intra Abdominal Infection Patients: A Retrospective Cohort Study. AB - BACKGROUND: Studies on the incidence and risk factors of thrombocytopenia among intra-abdominal infection patients remain absent, hindering efficacy assessments regarding thrombocytopenia prevention strategies. METHODS: We retrospectively studied 267 consecutively enrolled patients with intra-abdominal infections. Occurrence of thrombocytopenia was scanned for all patients. All-cause 28-day mortality was recorded. Variables from univariate analyses that were associated with occurrence of hospital-acquired thrombocytopenia were included in a multivariable logistic regression analysis to determine thrombocytopenia predictors. RESULTS: Median APACHE II score and SOFA score of the whole cohort was 12 and 3 respectively. The overall ICU mortality was 7.87% and the 28-day mortality was 8.98%. The incidence of thrombocytopenia among intra-abdominal infection patients was 21.73%. Regardless of preexisting or hospital-acquired one, thrombocytopenia is associated with an increased ICU mortality and 28-day mortality as well as length of ICU or hospital stay. A higher SOFA and ISTH score at admission were significant hospital-acquired thrombocytopenia risk factors. CONCLUSIONS: This is the first study to identify a high incidence of thrombocytopenia in patients with intra-abdominal infections. Our findings suggest that the inflammatory milieu of intra-abdominal infections may uniquely predispose those patients to thrombocytopenia. More effective thrombocytopenia prevention strategies are necessary in intra-abdominal infection patients. PMID- 26808493 TI - Are large portions responsible for the obesity epidemic? AB - Large portion sizes are frequently blamed for the obesity epidemic. In this paper, we examine the culpability of large portion sizes. It is true that portion sizes have increased during the obesity epidemic, but there is as yet little evidence that exposure to large portions produces significant weight gain. Furthermore, some evidence argues against the role of large portions in the obesity epidemic. For instance, the epidemic is largely a matter of weight gain among the upper half of the population weight distribution, whereas large portions appear to have an indiscriminate effect on food intake. Factors other than the size of individual meals may well be responsible for a great deal of the observed population weight gain. PMID- 26808494 TI - Fast and Rigorous Computation of Gene and Pathway Scores from SNP-Based Summary Statistics. AB - Integrating single nucleotide polymorphism (SNP) p-values from genome-wide association studies (GWAS) across genes and pathways is a strategy to improve statistical power and gain biological insight. Here, we present Pascal (Pathway scoring algorithm), a powerful tool for computing gene and pathway scores from SNP-phenotype association summary statistics. For gene score computation, we implemented analytic and efficient numerical solutions to calculate test statistics. We examined in particular the sum and the maximum of chi-squared statistics, which measure the strongest and the average association signals per gene, respectively. For pathway scoring, we use a modified Fisher method, which offers not only significant power improvement over more traditional enrichment strategies, but also eliminates the problem of arbitrary threshold selection inherent in any binary membership based pathway enrichment approach. We demonstrate the marked increase in power by analyzing summary statistics from dozens of large meta-studies for various traits. Our extensive testing indicates that our method not only excels in rigorous type I error control, but also results in more biologically meaningful discoveries. PMID- 26808495 TI - Yersinia spp. Identification Using Copy Diversity in the Chromosomal 16S rRNA Gene Sequence. AB - API 20E strip test, the standard for Enterobacteriaceae identification, is not sufficient to discriminate some Yersinia species for some unstable biochemical reactions and the same biochemical profile presented in some species, e.g. Yersinia ferderiksenii and Yersinia intermedia, which need a variety of molecular biology methods as auxiliaries for identification. The 16S rRNA gene is considered a valuable tool for assigning bacterial strains to species. However, the resolution of the 16S rRNA gene may be insufficient for discrimination because of the high similarity of sequences between some species and heterogeneity within copies at the intra-genomic level. In this study, for each strain we randomly selected five 16S rRNA gene clones from 768 Yersinia strains, and collected 3,840 sequences of the 16S rRNA gene from 10 species, which were divided into 439 patterns. The similarity among the five clones of 16S rRNA gene is over 99% for most strains. Identical sequences were found in strains of different species. A phylogenetic tree was constructed using the five 16S rRNA gene sequences for each strain where the phylogenetic classifications are consistent with biochemical tests; and species that are difficult to identify by biochemical phenotype can be differentiated. Most Yersinia strains form distinct groups within each species. However Yersinia kristensenii, a heterogeneous species, clusters with some Yersinia enterocolitica and Yersinia ferderiksenii/intermedia strains, while not affecting the overall efficiency of this species classification. In conclusion, through analysis derived from integrated information from multiple 16S rRNA gene sequences, the discrimination ability of Yersinia species is improved using our method. PMID- 26808496 TI - Comparative Proteomics Reveals Important Viral-Host Interactions in HCV-Infected Human Liver Cells. AB - Hepatitis C virus (HCV) poses a global threat to public health. HCV envelop protein E2 is the major component on the virus envelope, which plays an important role in virus entry and morphogenesis. Here, for the first time, we affinity purified E2 complex formed in HCV-infected human hepatoma cells and conducted comparative mass spectrometric analyses. 85 cellular proteins and three viral proteins were successfully identified in three independent trials, among which alphafetoprotein (AFP), UDP-glucose: glycoprotein glucosyltransferase 1 (UGT1) and HCV NS4B were further validated as novel E2 binding partners. Subsequent functional characterization demonstrated that gene silencing of UGT1 in human hepatoma cell line Huh7.5.1 markedly decreased the production of infectious HCV, indicating a regulatory role of UGT1 in viral lifecycle. Domain mapping experiments showed that HCV E2-NS4B interaction requires the transmembrane domains of the two proteins. Altogether, our proteomics study has uncovered key viral and cellular factors that interact with E2 and provided new insights into our understanding of HCV infection. PMID- 26808497 TI - Prucalopride for the Treatment of Symptomatic Uncomplicated Diverticular Disease of the Colon. PMID- 26808498 TI - Hepatocyte mitochondrial DNA drives nonalcoholic steatohepatitis by activation of TLR9. AB - Nonalcoholic steatohepatitis (NASH) is the most common liver disease in industrialized countries. NASH is a progressive disease that can lead to cirrhosis, cancer, and death, and there are currently no approved therapies. The development of NASH in animal models requires intact TLR9, but how the TLR9 pathway is activated in NASH is not clear. Our objectives in this study were to identify NASH-associated ligands for TLR9, establish the cellular requirement for TLR9, and evaluate the role of obesity-induced changes in TLR9 pathway activation. We demonstrated that plasma from mice and patients with NASH contains high levels of mitochondrial DNA (mtDNA) and intact mitochondria and has the ability to activate TLR9. Most of the plasma mtDNA was contained in microparticles (MPs) of hepatocyte origin, and removal of these MPs from plasma resulted in a substantial decrease in TLR9 activation capacity. In mice, NASH development in response to a high-fat diet required TLR9 on lysozyme-expressing cells, and a clinically applicable TLR9 antagonist blocked the development of NASH when given prophylactically and therapeutically. These data demonstrate that activation of the TLR9 pathway provides a link between the key metabolic and inflammatory phenotypes in NASH. PMID- 26808499 TI - PKCdelta inhibition normalizes the wound-healing capacity of diabetic human fibroblasts. AB - Abnormal fibroblast function underlies poor wound healing in patients with diabetes; however, the mechanisms that impair wound healing are poorly defined. Here, we evaluated fibroblasts from individuals who had type 1 diabetes (T1D) for 50 years or more (Medalists, n = 26) and from age-matched controls (n = 7). Compared with those from controls, Medalist fibroblasts demonstrated a reduced migration response to insulin, lower VEGF expression, and less phosphorylated AKT (p-AKT), but not p-ERK, activation. Medalist fibroblasts were also functionally less effective at wound closure in nude mice. Activation of the delta isoform of protein kinase C (PKCdelta) was increased in postmortem fibroblasts from Medalists, fibroblasts from living T1D subjects, biopsies of active wounds of living T1D subjects, and granulation tissues from mice with streptozotocin induced diabetes. Diabetes-induced PKCD mRNA expression was related to a 2-fold increase in the mRNA half-life. Pharmacologic inhibition and siRNA-mediated knockdown of PKCdelta or expression of a dominant-negative isoform restored insulin signaling of p-AKT and VEGF expression in vitro and improved wound healing in vivo. Additionally, increasing PKCdelta expression in control fibroblasts produced the same abnormalities as those seen in Medalist fibroblasts. Our results indicate that persistent PKCdelta elevation in fibroblasts from diabetic patients inhibits insulin signaling and function to impair wound healing and suggest PKCdelta inhibition as a potential therapy to improve wound healing in diabetic patients. PMID- 26808500 TI - Targeting human melanoma neoantigens by T cell receptor gene therapy. AB - In successful cancer immunotherapy, T cell responses appear to be directed toward neoantigens created by somatic mutations; however, direct evidence that neoantigen-specific T cells cause regression of established cancer is lacking. Here, we generated T cells expressing a mutation-specific transgenic T cell receptor (TCR) to target different immunogenic mutations in cyclin-dependent kinase 4 (CDK4) that naturally occur in human melanoma. Two mutant CDK4 isoforms (R24C, R24L) similarly stimulated T cell responses in vitro and were analyzed as therapeutic targets for TCR gene therapy. In a syngeneic HLA-A2-transgenic mouse model of large established tumors, we found that both mutations differed dramatically as targets for TCR-modified T cells in vivo. While T cells expanded efficiently and produced IFN-gamma in response to R24L, R24C failed to induce an effective antitumor response. Such differences in neoantigen quality might explain why cancer immunotherapy induces tumor regression in some individuals, while others do not respond, despite similar mutational load. We confirmed the validity of the in vivo model by showing that the melan-A-specific (MART-1 specific) TCR DMF5 induces rejection of tumors expressing analog, but not native, MART-1 epitopes. The described model allows identification of those neoantigens in human cancer that serve as suitable T cell targets and may help to predict clinical efficacy. PMID- 26808501 TI - Acidic pH increases airway surface liquid viscosity in cystic fibrosis. AB - Cystic fibrosis (CF) disrupts respiratory host defenses, allowing bacterial infection, inflammation, and mucus accumulation to progressively destroy the lungs. Our previous studies revealed that mucus with abnormal behavior impaired mucociliary transport in newborn CF piglets prior to the onset of secondary manifestations. To further investigate mucus abnormalities, here we studied airway surface liquid (ASL) collected from newborn piglets and ASL on cultured airway epithelia. Fluorescence recovery after photobleaching revealed that the viscosity of CF ASL was increased relative to that of non-CF ASL. CF ASL had a reduced pH, which was necessary and sufficient for genotype-dependent viscosity differences. The increased viscosity of CF ASL was not explained by pH independent changes in HCO3- concentration, altered glycosylation, additional pH induced disulfide bond formation, increased percentage of nonvolatile material, or increased sulfation. Treating acidic ASL with hypertonic saline or heparin largely reversed the increased viscosity, suggesting that acidic pH influences mucin electrostatic interactions. These findings link loss of cystic fibrosis transmembrane conductance regulator-dependent alkalinization to abnormal CF ASL. In addition, we found that increasing Ca2+ concentrations elevated ASL viscosity, in part, independently of pH. The results suggest that increasing pH, reducing Ca2+ concentration, and/or altering electrostatic interactions in ASL might benefit early CF. PMID- 26808503 TI - Cost-Effectiveness of Single- Versus Generic Multiple-Tablet Regimens for Treatment of HIV-1 Infection in the United States. AB - BACKGROUND: The possibility of incorporating generics into combination antiretroviral therapy and breaking apart once-daily single-tablet regimens (STRs), may result in less efficacious medications and/or more complex regimens with the expectation of marked monetary savings. A modeling approach that assesses the merits of such policies in terms of lifelong costs and health outcomes using adherence and effectiveness data from real-world U.S. settings. METHODS: A comprehensive computer-based microsimulation model was developed to assess the lifetime health (life expectancy and quality adjusted life-years- QALYs) and economic outcomes in HIV-1 infected patients initiating STRs compared with multiple-table regimens including generic medications where possible (gMTRs). The STRs considered included tenofovir disoproxil fumarate/emtricitabine and efavirenz or rilpivirine or elvitegravir/cobicistat. gMTRs substitutions included each counterpart to STRs, including generic lamivudine for emtricitabine and generic versus branded efavirenz. RESULTS: Life expectancy is estimated to be 1.301 years higher (discounted 0.619 QALY gain) in HIV-1 patients initiating a single-tablet regimen in comparison to a generic-based multiple-table regimen. STRs were associated with an average increment of $26,547.43 per patient in medication and $1,824.09 in other medical costs due to longer survival which were partially offset by higher inpatients costs ($12,035.61) with gMTRs treatment. Overall, STRs presented incremental lifetime costs of $16,335.91 compared with gMTRs, resulting in an incremental cost-effectiveness ratio of $26,383.82 per QALY gained. CONCLUSIONS: STRs continue to represent good value for money under contemporary cost-effectiveness thresholds despite substantial price reductions of generic medications in the U. S. PMID- 26808505 TI - Efficacy of Intensive Short-Term Dynamic Psychotherapy for Medically Unexplained Pain: A Pilot Three-Armed Randomized Controlled Trial Comparison with Mindfulness Based Stress Reduction. PMID- 26808502 TI - Lineage-affiliated transcription factors bind the Gata3 Tce1 enhancer to mediate lineage-specific programs. AB - The transcription factor GATA3 is essential for the genesis and maturation of the T cell lineage, and GATA3 dysregulation has pathological consequences. Previous studies have shown that GATA3 function in T cell development is regulated by multiple signaling pathways and that the Notch nuclear effector, RBP-J, binds specifically to the Gata3 promoter. We previously identified a T cell-specific Gata3 enhancer (Tce1) lying 280 kb downstream from the structural gene and demonstrated in transgenic mice that Tce1 promoted T lymphocyte-specific transcription of reporter genes throughout T cell development; however, it was not clear if Tce1 is required for Gata3 transcription in vivo. Here, we determined that the canonical Gata3 promoter is insufficient for Gata3 transcriptional activation in T cells in vivo, precluding the possibility that promoter binding by a host of previously implicated transcription factors alone is responsible for Gata3 expression in T cells. Instead, we demonstrated that multiple lineage-affiliated transcription factors bind to Tce1 and that this enhancer confers T lymphocyte-specific Gata3 activation in vivo, as targeted deletion of Tce1 in a mouse model abrogated critical functions of this T cell regulatory element. Together, our data show that Tce1 is both necessary and sufficient for critical aspects of Gata3 T cell-specific transcriptional activity. PMID- 26808504 TI - A Voxel-Based Morphometric MRI Study in Young Adults with Borderline Personality Disorder. AB - BACKGROUND: Increasing evidence has documented subtle changes in brain morphology and function in patients with borderline personality disorder (BPD). However, results of magnetic resonance imaging volumetry in patients with BPD are inconsistent. In addition, few researchers using voxel-based morphometry (VBM) have focused on attachment and childhood trauma in BPD. This preliminary study was performed to investigate structural brain changes and their relationships to attachment and childhood trauma in a homogenous sample of young adults with BPD. METHOD: We examined 34 young adults with BPD and 34 healthy controls (HCs) to assess regionally specific differences in gray matter volume (GMV) and gray matter concentration (GMC). Multiple regressions between brain volumes measured by VBM and attachment style questionnaire (ASQ) and childhood trauma questionnaire (CTQ) scores were performed. RESULTS: Compared with HCs, subjects with BPD showed significant bilateral increases in GMV in the middle cingulate cortex (MCC)/posterior cingulate cortex (PCC)/precuneus. GMC did not differ significantly between groups. In multiple regression models, ASQ insecure attachment scores were correlated negatively with GMV in the precuneus/MCC and middle occipital gyrus in HCs, HCs with more severe insecure attachment showed smaller volumes in precuneus/MCC and middle occipital gyrus, whereas no negative correlations between insecure attachment and GMV in any region were found in BPD group. In addition, CTQ total scores were not correlated with GMV in any region in the two groups respectively. CONCLUSIONS: Our findings fit with those of previous reports of larger precuneus GMV in patients with BPD, and suggest that GMV in the precuneus/MCC and middle occipital gyrus is associated inversely with insecure attachment style in HCs. Our finding of increased GMV in the MCC and PCC in patients with BPD compared with HCs has not been reported in previous VBM studies. PMID- 26808506 TI - Cigarette Smoke Disturbs the Survival of CD8+ Tc/Tregs Partially through Muscarinic Receptors-Dependent Mechanisms in Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: CD8+ T cells (Cytotoxic T cells, Tc) are known to play a critical role in the pathogenesis of smoking related airway inflammation including chronic obstructive pulmonary disease (COPD). However, how cigarette smoke directly impacts systematic CD8+ T cell and regulatory T cell (Treg) subsets, especially by modulating muscarinic acetylcholine receptors (MRs), has yet to be well elucidated. METHODS: Circulating CD8+ Tc/Tregs in healthy nonsmokers (n = 15), healthy smokers (n = 15) and COPD patients (n = 18) were evaluated by flow cytometry after incubating with anti-CD3, anti-CD8, anti-CD25, anti-Foxp3 antibodies. Peripheral blood T cells (PBT cells) from healthy nonsmokers were cultured in the presence of cigarette smoke extract (CSE) alone or combined with MRs agonist/antagonist for 5 days. Proliferation and apoptosis were evaluated by flow cytometry using Ki-67/Annexin-V antibodies to measure the effects of CSE on the survival of CD8+ Tc/Tregs. RESULTS: While COPD patients have elevated circulating percentage of CD8+ T cells, healthy smokers have higher frequency of CD8+ Tregs. Elevated percentages of CD8+ T cells correlated inversely with declined FEV1 in COPD. CSE promoted the proliferation and inhibited the apoptosis of CD8+ T cells, while facilitated both the proliferation and apoptosis of CD8+ Tregs. Notably, the effects of CSE on CD8+ Tc/Tregs can be mostly simulated or attenuated by muscarine and atropine, the MR agonist and antagonist, respectively. However, neither muscarine nor atropine influenced the apoptosis of CD8+ Tregs. CONCLUSION: The results imply that cigarette smoking likely facilitates a proinflammatory state in smokers, which is partially mediated by MR dysfunction. The MR antagonist may be a beneficial drug candidate for cigarette smoke-induced chronic airway inflammation. PMID- 26808507 TI - N-Acetyl Cysteine Depletes Reactive Oxygen Species and Prevents Dental Monomer Induced Intrinsic Mitochondrial Apoptosis In Vitro in Human Dental Pulp Cells. AB - PURPOSE: To investigate the involvement of intrinsic mitochondrial apoptosis in dental monomer-induced cytotoxicity and the influences of N-acetyl cysteine (NAC) on this process. METHODS: Human dental pulp cells (hDPCs) were exposed to several dental monomers in the absence or presence of NAC, and cell viability, intracellular redox balance, morphology and function of mitochondria and key indicators of intrinsic mitochondrial apoptosis were evaluated using various commercial kits. RESULTS: Dental monomers exerted dose-dependent cytotoxic effects on hDPCs. Concomitant to the over-production of reactive oxygen species (ROS) and depletion of glutathione (GSH), differential changes in activities of superoxide dismutase, glutathione peroxidase, and catalase were detected. Apoptosis, as indicated by positive Annexin V/propidium iodide (PI) staining and activation of caspase-3, was observed after dental monomer treatment. Dental monomers impaired the morphology and function of mitochondria, and induced intrinsic mitochondrial apoptosis in hDPCs via up-regulation of p53, Bax and cleaved caspase-3, and down-regulation of Bcl-2. NAC restored cell viability, relieved oxidative stress and blocked the apoptotic effects of dental monomers. CONCLUSIONS: Dental monomers induced oxidative stress and mitochondrial intrinsic apoptosis in hDPCs. NAC could reduce the oxidative stress and thus protect hDPCs against dental monomer-induced apoptosis. PMID- 26808508 TI - A New Anaesthetic Protocol for Adult Zebrafish (Danio rerio): Propofol Combined with Lidocaine. AB - BACKGROUND: The increasing use of zebrafish model has not been accompanied by the evolution of proper anaesthesia for this species in research. The most used anaesthetic in fishes, MS222, may induce aversion, reduction of heart rate, and consequently high mortality, especially during long exposures. Therefore, we aim to explore new anaesthetic protocols to be used in zebrafish by studying the quality of anaesthesia and recovery induced by different concentrations of propofol alone and in combination with different concentrations of lidocaine. MATERIAL AND METHODS: In experiment A, eighty-three AB zebrafish were randomly assigned to 7 different groups: control, 2.5 (2.5P), 5 (5P) or 7.5 MUg/ml (7.5P) of propofol; and 2.5 MUg/ml of propofol combined with 50, (P/50L), 100 (P/100L) or 150 MUg/ml (P/150L) of lidocaine. Zebrafish were placed in an anaesthetic water bath and time to lose the equilibrium, reflex to touch, reflex to a tail pinch, and respiratory rate were measured. Time to gain equilibrium was also assessed in a clean tank. Five and 24 hours after anaesthesia recovery, zebrafish were evaluated concerning activity and reactivity. Afterwards, in a second phase of experiments (experiment B), the best protocol of the experiment A was compared with a new group of 8 fishes treated with 100 mg/L of MS222 (100M). RESULTS: In experiment A, only different concentrations of propofol/lidocaine combination induced full anaesthesia in all animals. Thus only these groups were compared with a standard dose of MS222 in experiment B. Propofol/lidocaine induced a quicker loss of equilibrium, and loss of response to light and painful stimuli compared with MS222. However zebrafish treated with MS222 recovered quickly than the ones treated with propofol/lidocaine. CONCLUSION: In conclusion, propofol/lidocaine combination and MS222 have advantages in different situations. MS222 is ideal for minor procedures when a quick recovery is important, while propofol/lidocaine is best to induce a quick and complete anaesthesia. PMID- 26808509 TI - Heterogeneous Distribution of Fetal Microchimerism in Local Breast Cancer Environment. AB - Fetal cells enter maternal circulation during pregnancy and persist in the woman's body for decades, achieving a form of physiological microchimerism. These cells were also evidenced in tumors. We investigated the frequency and concentration of fetal microchimerism in the local breast cancer environment. From 19 patients with confirmed breast neoplasia, after breast surgical resection, we collected three fresh specimens from the tumor core, breast tissue at tumor periphery, and adjacent normal breast tissue. The presence of male DNA was analyzed with a quantitative PCR assay for the sex determining region gene (SRY) gene. In the group of women who had given birth to at least one son, we detected fetal microchimerism in 100% of samples from tumors and their periphery and in 64% (9 of 14) of those from normal breast tissue. The tissues from the tumor and its periphery carry a significantly increased number of SRY copies compared to its neighboring common breast tissue (p = 0.005). The median of the normalized SRY-signal was about 77 (range, 3.2-21467) and 14-fold (range, 1.3 2690) greater in the tumor and respectively in the periphery than in the normal breast tissue. In addition, the relative expression of the SRY gene had a median 5.5 times larger in the tumor than in its periphery (range, 1.1-389.4). We found a heterogeneous distribution of fetal microchimerism in breast cancer environment. In women with sons, breast neoplasia harbors male cells at significantly higher levels than in peripheral and normal breast tissue. PMID- 26808511 TI - Video Abstracts: A Fun, Easy Way to Capture Your Audience: Try it! PMID- 26808510 TI - The Prognostic Value of Peak Cardiac Power Output in Chinese Patients with Chronic Heart Failure. AB - BACKGROUND: Cardiopulmonary exercise testing has been widely used to risk stratify patients with chronic heart failure (CHF). Peak oxygen consumption (peakVO2) was regarded as a powerful predictor of survival, as it is a surrogate for peak cardiac output (CO), which by most is considered the "true" measure of heart failure. Therefore, it is reasonable to hypothesize that CO is an even stronger predictor than peak VO2. The present study is aimed to investigate the prognostic value of peak cardiac power output (peak CPO) in comparison with peakVO2 in Chinese patients with CHF. METHODS: Participants provided written informed consent to participate in this study. Totally 129 patients with CHF underwent symptom-limited cardiopulmonary exercise testing (CPET), with mean age 59.1 +/- 11.4 years, 87.6% male, 57.4% ischemic etiology, body mass index (BMI) 24.7 +/- 3.7 kg/m(2) and LVEF 38 +/- 9%. CO was measured using an inert gas rebreathing method. The primary endpoints are cardiac deaths. RESULTS: Over median 33.7-month follow-up, 19 cardiac deaths were reported. Among peak VO2,VE/VCO2 slope and Peak CPO, their area under ROC were 0.64, 0.67, 0.68, respectively (Rho<0.05).The optimal thresholds for predicting cardiac deaths were peak VO2 <= 13.4 ml.kg(-1).min(-1), and VE/VCO2 slope >= 39.3 and peak CPO<= 1.1 respectively by ROC analysis. Finally, in patients with a peak VO2 <= 13.4 ml.kg( 1).min(-1) those with peak CPO>1.1W had better survival than those with peak CPO <= 1.1W. However, by multivariate analysis adjusted for age, sex, BMI, resting heart rate, LVMI, LVEF, Peak CPO was not an independent predictor of cardiac deaths (P> 0.05). CONCLUSIONS: Peak CPO was not a predictor of cardiac death in Chinese CHF patients. PMID- 26808512 TI - A new global initiative: the International Neonatal Consortium. PMID- 26808514 TI - Guest Editorial: Special Series in Respiratory Management. PMID- 26808515 TI - Neonatal Extracorporeal Membrane Oxygenation: Update on Management Strategies and Long-Term Outcomes. AB - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) can be deployed to support patients with severe cardiorespiratory failure unresponsive to conventional medical interventions. Neonatal trials have demonstrated that ECMO is an effective treatment of severe respiratory failure, with acceptable cognitive and functional outcomes. Technological advances in ECMO have resulted in improved safety and accessibility, contributing to decreased morbidity and improved survival of increasingly complex patients requiring ECMO support. PURPOSE: This review aims to describe the innovations in ECMO technology and management in the neonatal population in the last decade. The long-term outcomes of neonatal patients requiring ECMO support will be discussed. SEARCH STRATEGY: Relevant clinical trials from MEDLINE and the Cochrane Library were identified. The following key words were used: ECMO, infant, neonate, and outcomes. FINDINGS: Challenges still remain in supporting the premature and/or low-birth-weight infant with severe respiratory failure, as well as infants with congenital diaphragmatic hernia. Neonatal ECMO survivors can present with neurodevelopmental and respiratory problems, which become more prominent with time. IMPLICATIONS FOR PRACTICE: While newer technologies have led to fewer neonates with respiratory failure progressing to ECMO, it remains an important tool to in those who have failed conventional therapies. Given the presence of neurodevelopmental problems in neonatal ECMO survivors, multidisciplinary follow-up targeting motor performance, exercise capacity, behavior, and subtle learning deficits is warranted. IMPLICATIONS FOR RESEARCH: With the overall decreasing use of neonatal ECMO, ECMO centers must find ways to maintain their expertise in the light of lower patient volumes amidst complex patient physiology. PMID- 26808516 TI - Family Teaching Toolbox. A Parent's Guide to Congenital Cytomegalovirus. PMID- 26808518 TI - The Spread of Dengue in an Endemic Urban Milieu--The Case of Delhi, India. AB - BACKGROUND: Dengue is a major international public health concern, one of the most important arthropod-borne diseases. More than 3.5 billion people are at risk of dengue infection and there are an estimated 390 million dengue infections annually. This prolific increase has been connected to societal changes such as population growth and increasing urbanization generating intense agglomeration leading to proliferation of synanthropic mosquito species. Quantifying the spatio temporal epidemiology of dengue in large cities within the context of a Geographic Information System is a first step in the identification of socio economic risk factors. METHODOLOGY/PRINCIPAL FINDINGS: This Project has been approved by the ethical committee of Institut Pasteur. Data has been anonymized and de-identified prior to geolocalisation and analysis. A GIS was developed for Delhi, enabling typological characterization of the urban environment. Dengue cases identified in the Delhi surveillance system from 2008 to 2010 were collated, localised and embedded within this GIS. The spatio-temporal distribution of dengue cases and extent of clustering were analyzed. Increasing distance from the forest in Delhi reduced the risk of occurrence of a dengue case. Proximity to a hospital did not increase risk of a notified dengue case. Overall, there was high heterogeneity in incidence rate within areas with the same socio-economical profiles and substantial inter-annual variability. Dengue affected the poorest areas with high density of humans, but rich areas were also found to be infected, potentially because of their central location with respect to the daily mobility network of Delhi. Dengue cases were highly clustered in space and there was a strong relationship between the time of introduction of the virus and subsequent cluster size. At a larger scale, earlier introduction predicted the total number of cases. CONCLUSIONS/SIGNIFICANCE: DENV epidemiology within Delhi has a forest fire signature. The stochastic nature of this invasion process likely smothers any detectable socio-economic risk factors. However, the significant finding that the size of the dengue case cluster depends on the timing of its emergence emphasizes the need for early case detection and implementation of effective mosquito control. A better understanding of the role of population mobility in contributing to dengue risk could also help focus control on areas at particular risk of dengue virus importation. PMID- 26808519 TI - Psychosocial Intervention Is Associated with Altered Emotion Processing: An Event Related Potential Study in At-Risk Adolescents. AB - Emotion processing is vital for healthy adolescent development, and impaired emotional responses are associated with a number of psychiatric disorders. However, it is unclear whether observed differences between psychiatric populations and healthy controls reflect modifiable variations in functioning (and thus could be sensitive to changes resulting from intervention) or stable, non-modifiable, individual differences. The current study therefore investigated whether the Late Positive Potential (LPP; a neural index of emotion processing) can be used as a marker of therapeutic change following psycho-social intervention. At-risk male adolescents who had received less than four months intervention (minimal-intervention, N = 32) or more than nine months intervention (extended-intervention, N = 32) passively viewed emotional images whilst neural activity was recorded using electroencephalography. Significant differences in emotion processing, indicated by the LPP, were found between the two groups: the LPP did not differ according to valence in the minimal-intervention group, whereas the extended-intervention participants showed emotion processing in line with low risk populations (enhanced LPP for unpleasant images versus other images). Further, an inverse relationship between emotional reactivity (measured via the LPP) and antisocial behaviour was observed in minimal-intervention participants only. The data therefore provide preliminary cross-sectional evidence that abnormal neural responses to emotional information may be normalised following psychosocial intervention. Importantly, this study uniquely suggests that, in future randomised control trials, the LPP may be a useful biomarker to measure development and therapeutic change. PMID- 26808521 TI - Gravid Spot Predicts Developmental Progress and Reproductive Output in a Livebearing Fish, Gambusia holbrooki. AB - In most livebearing fish, the gravid spot is an excellent marker to identify brooding females, however its use to predict progress of embryonic development, brood size, timing of parturition and overall reproductive potential of populations remain unexplored. Therefore, to understand these relationships, this study quantified visual attributes (intensity and size) of the gravid spot in relation to key internal development in Gambusia holbrooki. Observations show that the colour of the gravid spot arises from progressive melanisation on the surface of the ovarian sac at its hind margin, rather than melanisation of the developing embryos or the skin of the brooding mother. More importantly, the gravid spot intensity and size were closely linked with both developmental stages and clutch size, suggesting their reliable use as external surrogates of key internal developmental in the species. Using predictive consistency of the gravid spot, we also determined the effect of rearing temperature (23 degrees C and 25 degrees C) on gestation period and parturition behaviour. The results show that gestation period was significantly reduced (F = 364.58; df = 1,48; P ? 0.05) at 25 degrees C. However there was no significant difference in average number of fry parturated in the two temperature groups (P<0.05), reaffirming that gravid spot intensity is a reliable predictor of reproductive output. The parturition in the species occurred predominantly in the morning and in contrast to earlier reports, tails of the fry emerged first with a few exceptions of head-first, twin and premature births. This study demonstrates utility of the gravid spot for downstream reproductive investigations in a live-bearing fish both in the field and laboratory. The reproducibility of the relationships (intensity with both developmental stage and clutch size), imply that they are also relevant to wild populations that experience varying temperature climes and stressors, significant deviations of which may serve as indicators of environmental health and climate variability. PMID- 26808520 TI - Ca2+/Calmodulin-Dependent Protein Kinase Kinases (CaMKKs) Effects on AMP Activated Protein Kinase (AMPK) Regulation of Chicken Sperm Functions. AB - Sperm require high levels of energy to ensure motility and acrosome reaction (AR) accomplishment. The AMP-activated protein kinase (AMPK) has been demonstrated to be strongly involved in the control of these properties. We address here the question of the potential role of calcium mobilization on AMPK activation and function in chicken sperm through the Ca(2+)/calmodulin-dependent protein kinase kinases (CaMKKs) mediated pathway. The presence of CaMKKs and their substrates CaMKI and CaMKIV was evaluated by western-blotting and indirect immunofluorescence. Sperm were incubated in presence or absence of extracellular Ca(2+), or of CaMKKs inhibitor (STO-609). Phosphorylations of AMPK, CaMKI, and CaMKIV, as well as sperm functions were evaluated. We demonstrate the presence of both CaMKKs (alpha and beta), CaMKI and CaMKIV in chicken sperm. CaMKKalpha and CaMKI were localized in the acrosome, the midpiece, and at much lower fluorescence in the flagellum, whereas CaMKKbeta was mostly localized in the flagellum and much less in the midpiece and the acrosome. CaMKIV was only present in the flagellum. The presence of extracellular calcium induced an increase in kinases phosphorylation and sperm activity. STO-609 reduced AMPK phosphorylation in the presence of extracellular Ca(2+) but not in its absence. STO-609 did not affect CaMKIV phosphorylation but decreased CaMKI phosphorylation and this inhibition was quicker in the presence of extracellular Ca(2+) than in its absence. STO-609 efficiently inhibited sperm motility and AR, both in the presence and absence of extracellular Ca(2+). Our results show for the first time the presence of CaMKKs (alpha and beta) and one of its substrate, CaMKI in different subcellular compartments in germ cells, as well as the changes in the AMPK regulation pathway, sperm motility and AR related to Ca(2+) entry in sperm through the Ca(2+)/CaM/CaMKKs/CaMKI pathway. The Ca(2+)/CaMKKs/AMPK pathway is activated only under conditions of extracellular Ca(2+) entry in the cells. PMID- 26808522 TI - Genetic Diversity and Population Structure of Leishmania infantum from Southeastern France: Evaluation Using Multi-Locus Microsatellite Typing. AB - In the south of France, Leishmania infantum is responsible for numerous cases of canine leishmaniasis (CanL), sporadic cases of human visceral leishmaniasis (VL) and rare cases of cutaneous and muco-cutaneous leishmaniasis (CL and MCL, respectively). Several endemic areas have been clearly identified in the south of France including the Pyrenees-Orientales, Cevennes (CE), Provence (P), Alpes Maritimes (AM) and Corsica (CO). Within these endemic areas, the two cities of Nice (AM) and Marseille (P), which are located 150 km apart, and their surroundings, concentrate the greatest number of French autochthonous leishmaniasis cases. In this study, 270 L. infantum isolates from an extended time period (1978-2011) from four endemic areas, AM, P, CE and CO, were assessed using Multi-Locus Microsatellite Typing (MLMT). MLMT revealed a total of 121 different genotypes with 91 unique genotypes and 30 repeated genotypes. Substantial genetic diversity was found with a strong genetic differentiation between the Leishmania populations from AM and P. However, exchanges were observed between these two endemic areas in which it seems that strains spread from AM to P. The genetic differentiations in these areas suggest strong epidemiological structuring. A model-based analysis using STRUCTURE revealed two main populations: population A (consisting of samples primarily from the P and AM endemic areas with MON-1 and non-MON-1 strains) and population B consisting of only MON-1 strains essentially from the AM endemic area. For four patients, we observed several isolates from different biological samples which provided insight into disease relapse and re-infection. These findings shed light on the transmission dynamics of parasites in humans. However, further data are required to confirm this hypothesis based on a limited sample set. This study represents the most extensive population analysis of L. infantum strains using MLMT conducted in France. PMID- 26808523 TI - Postprandial Hypertriglyceridemia Predicts Development of Insulin Resistance Glucose Intolerance and Type 2 Diabetes. AB - Insulin resistance (IR) and type 2 diabetes mellitus (T2DM) have been found to be associated with postprandial hypertriglyceridemia (PPHTg). However, whether PPHTg can cause IR and diabetes is not clear. We therefore investigated the role of PPHTg in development of T2DM in rat model of T2DM. 96 male Wistar rats were randomized into four groups (24 rats each). Control Group A, high sucrose diet (HSD) Group B, HSD+Pioglitazone (10 mg/kg/day) Group C and HSD+Atorvastatin (20 mg/kg/day) Group D. Fat and glucose tolerance tests were done at regular intervals in all groups besides insulin and body weight measurement. At 26 weeks, low dose streptozotocin (15 mg/kg, i.p.) was given to half of the rats. All rats were followed up till 48 weeks. PPHTg developed as early as week 2 in Group B and stabilized by week 14. Group B displayed highest PPHTg compared to other groups. Atorvastatin treatment (Group D) abolished PPHTg which became comparable to controls, pioglitazone treatment partially blunted PPHTg resulting in intermediate PPHTg. Group B with highest PPHTg showed highest subsequent IR, glucose intolerance (GI) and highest incidence of prediabetes at week 26 and diabetes at week 34 and 46 compared to other groups. Group D rats displayed lower IR, GI, low incidence of prediabetes and diabetes at these time points compared to Groups B and C. ROC analysis showed that triglyceride area under the curve of each time point significantly predicts the risk of diabetes. Present study provides the evidence that PPHTg predicts the development of IR, GI and T2DM in rat model of diet induced T2DM. PMID- 26808524 TI - Dopaminergic Receptors and Tyrosine Hydroxylase Expression in Peripheral Blood Mononuclear Cells: A Distinct Pattern in Central Obesity. AB - BACKGROUND: Dopamine (DA) may be involved in central obesity (CO), an inflammatory condition, through its role in the central nervous system and in periphery, where it may affect immune cell function through five different DA receptors (DR). Whether dopaminergic pathways in peripheral immune cells are implicated in the inflammatory condition linked to CO is however unknown. METHODS: In a cohort of blood donors with and without CO, categorized by waist circumference (WC) (CO: WC >= 0.80 m in women and >= 0.94 m in men), we studied the expression of DR and tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of DA, in peripheral blood mononuclear cells (PBMCs) and their relation with anthropometric and metabolic/endocrine and inflammatory parameters. DR D1-5 and TH expression was assessed by semi quantitative real-time PCR. As inflammatory markers we investigated the immunophenotype of monocyte subsets by flow cytometry, staining for CD14, CD16, CD11b and CD36. RESULTS: CO individuals showed higher plasma levels of leptin and higher inflammatory pattern of monocytes compared with non-CO. PBMC expression of DR D2, DR D4 and DR D5 as well as of TH were lower in CO in comparison with non-CO. DR D2, and DR D5 expression correlated with lower WC and weight, and with lower inflammatory pattern of monocytes, and TH expression correlated with lower WC. DR D4 expression correlated with lower plasma levels of glycosylated hemoglobin, and DR D2 expression correlated with lower CO. CONCLUSIONS: Results show that CO is associated with peripheral inflammation and downregulation of dopaminergic pathways in PBMCs, possibly suggesting DR expressed on immune cells as pharmacological targets in obesity for better metabolic outcome. PMID- 26808525 TI - ECM-Regulator timp Is Required for Stem Cell Niche Organization and Cyst Production in the Drosophila Ovary. AB - The extracellular matrix (ECM) is a pivotal component adult tissues and of many tissue-specific stem cell niches. It provides structural support and regulates niche signaling during tissue maintenance and regeneration. In many tissues, ECM remodeling depends on the regulation of MMP (matrix metalloproteinase) activity by inhibitory TIMP (tissue inhibitors of metalloproteinases) proteins. Here, we report that the only Drosophila timp gene is required for maintaining the normal organization and function of the germline stem cell niche in adult females. timp mutant ovaries show reduced levels of both Drosophila Collagen IV alpha chains. In addition, tissue stiffness and the cellular organization of the ovarian niche are affected in timp mutants. Finally, loss of timp impairs the ability of the germline stem cell niche to generate new cysts. Our results demonstrating a crucial role for timp in tissue organization and gamete production thus provide a link between the regulation of ECM metabolism and tissue homeostasis. PMID- 26808526 TI - The Effects of Experimental Sleep Apnea on Cardiac and Respiratory Functions in 6 and 18 Month Old Dystrophic (mdx) Mice. AB - Duchenne muscular dystrophy (DMD) is a fatal disease where over 90% of patients succumb to respiratory or cardiac failure. Sleep apnea and sleep disordered breathing (SDB) are noted in a plurality of DMD patients, and the resulting nocturnal episodic hypoxia (EH) cannot be ruled out as a contributing factor to cardiac and respiratory dysfunction. In this study, we investigated the impact of long-term episodic hypoxia, which mimics the cyclic hypoxia seen in sleep apnea, on cardiac and respiratory function in a murine model of DMD (mdx mice). Since the severity and prevalence of sleep apnea in DMD increases with age, we studied the impact of EH on young (6-month) and on older (18-month) mdx mice. Mice were either exposed for 12 weeks to EH (8 hours/day, 5 days/week) or to room air. We noted a significant increase in left ventricular (LV) dilatation (transthoracic echocardiography) on EH exposure in both age groups, but reduced LV contractility was seen only in 6-month old mice. With EH exposure, an increased fibrosis (hydroxyproline) was noted in both cardiac and diaphragm muscle in 18-month but not 6-month old mice. No significant change in relative diaphragm strength (in vitro) was noted on EH exposure in 18-month old mice. In contrast, EH exposed 6 month old mice showed a significant increase in relative diaphragm strength. EH exposure did not result in any significant change in ventilatory parameters (barometric plethysmography) in awake 6-month old mdx mice. In contrast, 18-month old mdx mice showed considerable ventilatory dysfunction, consistent with reduced ventilatory reserve. Our findings highlight that sleep apnea impacts respiratory and cardiac function in muscular dystrophy, and that EH can have divergent effects on both systems. To our knowledge, this is the first comprehensive study to investigate the impact of EH on cardiac and respiratory function in mdx mice. PMID- 26808527 TI - Genomic Motifs as a Novel Indicator of the Relationship between Strains Isolated from the Epidemic of Porcine Epidemic Diarrhea in 2013-2014. AB - Porcine epidemic diarrhea virus (PEDV) is a positive-sense RNA virus that causes infectious gastroenteritis in pigs. Following a PED outbreak that occurred in China in 2010, the disease was identified for the first time in the United States in April 2013, and was reported in many other countries worldwide from 2013 to 2014. As a novel approach to elucidate the epidemiological relationship between PEDV strains, we explored their genome sequences to identify the motifs that were shared within related strains. Of PED outbreaks reported in many countries during 2013-2014, 119 PEDV strains in Japan, USA, Canada, Mexico, Germany, and Korea were selected and used in this study. We developed a motif mining program, which aimed to identify a specific region of the genome that was exclusively shared by a group of PEDV strains. Eight motifs were identified (M1-M8) and they were observed in 41, 9, 18, 6, 10, 14, 2, and 2 strains, respectively. Motifs M1-M6 were shared by strains from more than two countries, and seemed to originate from one PEDV strain, Indiana12.83/USA/2013, among the 119 strains studied. BLAST search for motifs M1-M6 revealed that M3-M5 were almost identical to the strain ZMDZY identified in 2011 in China, while M1 and M2 were similar to other Chinese strains isolated in 2011-2012. Consequently, the PED outbreaks in these six countries may be closely related, and multiple transmissions of PEDV strains between these countries may have occurred during 2013-2014. Although tools such as phylogenetic tree analysis with whole genome sequences are increasingly applied to reveal the connection between isolates, its interpretation is sometimes inconclusive. Application of motifs as a tool to examine the whole genome sequences of causative agents will be more objective and will be an explicit indicator of their relationship. PMID- 26808528 TI - Evaporative Cooler Use Influences Temporal Indoor Relative Humidity but Not Dust Mite Allergen Levels in Homes in a Semi-Arid Climate. AB - Concerns about energy consumption and climate change make residential evaporative coolers a popular alternative to central air conditioning in arid and semi-arid climates. However, evaporative coolers have been shown to significantly increase indoor relative humidity and dust mite allergen levels in some studies, while showing no association in other studies. Improved measurement of temporal fluctuations in indoor relative humidity may help identify factors that promote mite growth in homes in dry climates. Dust samples and continuous indoor relative humidity measurements were collected from homes with central air conditioning and homes with evaporative coolers in Utah. Samples were collected over two seasons, winter/spring (Jan-Apr) and summer (July-Sept), 2014. Dust samples were analyzed for Der p 1 and Der f 1 using a two-site monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) analysis. Housing characteristics including age of home, occupant density, and age of mattresses, furniture, and carpeting were also measured. Positive Der p 1 or Der f 1 samples were found in 25.0% of the homes and there was no difference in mean allergen levels by type of air conditioning. Indoor relative humidity was significantly higher in homes with evaporative coolers compared to those with central air conditioning during the summer. Homes with evaporative coolers also spent significantly more time during summer above 55.0% and 65.0% relative humidity compared to central air homes, but not above 75.0%. Findings from this study suggest that increased humidity from evaporative coolers may not be sufficient to exceed the critical equilibrium humidity or maintain humidity excursions for sufficient duration in relatively larger single family homes in semi-arid climates to support mite growth and reproduction. PMID- 26808529 TI - Correction: Combining XCO2 Measurements Derived from SCIAMACHY and GOSAT for Potentially Generating Global CO2 Maps with High Spatiotemporal Resolution. PMID- 26808530 TI - Dignity and Distress towards the End of Life across Four Non-Cancer Populations. AB - OBJECTIVE: The purpose of this study was to identify four non-cancer populations that might benefit from a palliative approach; and describe and compare the prevalence and patterns of dignity related distress across these diverse clinical populations. DESIGN: A prospective, multi-site approach was used. SETTING: Outpatient clinics, inpatient facilities or personal care homes, located in Winnipeg, Manitoba and Edmonton, Alberta, Canada. PARTICIPANTS: Patients with advanced Amyotrophic Lateral Sclerosis (ALS), Chronic Obstructive Pulmonary Disease (COPD), End Stage Renal Disease (ESRD); and the institutionalized alert frail elderly. MAIN OUTCOME MEASURE: In addition to standardized measures of physical, psychological and spiritual aspects of patient experience, the Patient Dignity Inventory (PDI). RESULTS: Between February 2009 and December 2012, 404 participants were recruited (ALS, 101; COPD, 100; ESRD, 101; and frail elderly, 102). Depending on group designation, 35% to 58% died within one year of taking part in the study. While moderate to severe loss of sense of dignity did not differ significantly across the four study populations (4-11%), the number of PDI items reported as problematic was significantly different i.e. ALS 6.2 (5.2), COPD 5.6 (5.9), frail elderly 3.0 (4.4) and ESRD 2.3 (3.9) [p < .0001]. Each of the study populations also revealed unique and distinct patterns of physical, psychological and existential distress. CONCLUSION: People with ALS, COPD, ESRD and the frail elderly face unique challenges as they move towards the end of life. Knowing the intricacies of distress and how they differ across these groups broadens our understanding of end-of-life experience within non-cancer populations and how best to meet their palliative care needs. PMID- 26808531 TI - Molecular Evidence for the Hybrid Origin of Ilex dabieshanensis (Aquifoliaceae). AB - Ilex, the largest genus of dioecious woody plants, is a good study system to assess the role of hybridization in speciation and evolution. Ilex dabieshanensis, a tree endemic to Dabieshan Mountains region, was initially described as a new species. Based on morphological intermediacy and sympatric distribution with its putative parental species, I. cornuta and I. latifolia, we proposed it as a natural hybrid between them. In this study, we sequenced one chloroplast intergenic spacer (trnH-psbA) and two nuclear genes (gapC and nepGS) in I. dabieshanensis and its putative parental species to test the hybrid origin hypothesis. Our results showed that there were one to two differentially fixed sequence differences between I. cornuta and I. latifolia at the two nuclear genes. Twelve of the 14 individuals of I. dabieshanensis exhibited additivity in chromatograms on these differentially fixed sites at both nuclear genes, and the remaining two exhibited additivity in chromatograms on the fixed site at only the nepGS gene. Except one haplotype of I. cornuta at the nepGS gene, all of the haplotypes of I. cornuta at the two nuclear genes were well separated from those of I. latifolia, and most haplotypes of I. dabieshanensis were shared with those of I. cornuta and I. latifolia. Phylogenetic analysis of these haplotypes was largely consistent with haplotype network analysis. I. cornuta and I. latifolia differed by two nucleotide substitutions in the chloroplast intergenic spacer, and 12 individuals of I. dabieshanensis had the same sequences as I. latifolia, while the remaining two were identical with I. cornuta. The molecular data provide convincing evidence for the hybrid origin of I. dabieshanensis and asymmetrical direction of hybridization. One haplotype of I. cornuta at the nepGS gene was nested with those of I. latifolia, indicating introgression to I. cornuta. PMID- 26808532 TI - Intentional Weight Loss and Longevity in Overweight Patients with Type 2 Diabetes: A Population-Based Cohort Study. AB - OBJECTIVE: This study examined the influence of weight loss on long-term morbidity and mortality in overweight (BMI>=25 kg/m2) patients with type 2 diabetes, and tested the hypothesis that therapeutic intentional weight loss supervised by a medical doctor prolongs life and reduces the risk for cardiovascular disease in these patients. METHODS: This is a 19 year cohort study of patients in the intervention arm of the randomized clinical trial Diabetes Care in General Practice. Weight and prospective intentions for weight loss were monitored every third month for six years in 761 consecutive patients (>=40 years) newly diagnosed with diabetes in general practices throughout Denmark in 1989-92. Multivariable Cox regression was used to estimate the association between weight change during the monitoring period (year 0 to 6) and the outcomes during the succeeding 13 years (year 6 to 19) in 444 patients who were overweight at diagnosis and alive at the end of the monitoring period (year 6). The analysis was adjusted for age, sex, education, BMI at diagnosis, change in smoking, change in physical activity, change in medication, and the Charlson comorbidity 6-year score. Outcomes were from national registers. RESULTS: Overall, weight loss regardless of intention was an independent risk factor for increased all-cause mortality (P<0.01). The adjusted hazard ratio for all-cause mortality, cardiovascular mortality, and cardiovascular morbidity attributable to an intentional weight loss of 1 kg/year was 1.20 (95%CI 0.97-1.50, P = 0.10), 1.26 (0.93-1.72, P = 0.14), and 1.06 (0.79-1.42, P = 0.71), respectively. Limiting the analysis to include only those patients who survived the first 2 years after the monitoring period did not substantially change these estimates. A non-linear spline estimate indicated a V-like association between weight change and all cause mortality, suggesting the best prognosis for those who maintained their weight. CONCLUSIONS: In this population-based cohort of overweight patients with type 2 diabetes, successful therapeutic intentional weight loss, supervised by a doctor over six years, was not associated with reduced all-cause mortality or cardiovascular morbidity/mortality during the succeeding 13 years. PMID- 26808533 TI - Cysteine Metabolism and Oxidative Processes in the Rat Liver and Kidney after Acute and Repeated Cocaine Treatment. AB - The role of cocaine in modulating the metabolism of sulfur-containing compounds in the peripheral tissues is poorly understood. In the present study we addressed the question about the effects of acute and repeated (5 days) cocaine (10 mg/kg i.p.) administration on the total cysteine (Cys) metabolism and on the oxidative processes in the rat liver and kidney. The whole pool of sulfane sulfur, its bound fraction and hydrogen sulfide (H2S) were considered as markers of anaerobic Cys metabolism while the sulfate as a measure of its aerobic metabolism. The total-, non-protein- and protein- SH group levels were assayed as indicators of the redox status of thiols. Additionally, the activities of enzymes involved in H2S formation (cystathionine gamma-lyase, CSE; 3-mercaptopyruvate sulfurtransferase, 3-MST) and GSH metabolism (gamma-glutamyl transpeptidase, gamma-GT; glutathione S-transferase, GST) were determined. Finally, we assayed the concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA) as markers of oxidative stress and lipid peroxidation, respectively. In the liver, acute cocaine treatment, did not change concentrations of the whole pool of sulfane sulfur, its bound fraction, H2S or sulfate but markedly decreased levels of non-protein SH groups (NPSH), ROS and GST activity while gamma-GT was unaffected. In the kidney, acute cocaine significantly increased concentration of the whole pool of sulfane sulfur, reduced the content of its bound fraction but H2S, sulfate and NPSH levels were unchanged while ROS and activities of GST and gamma-GT were reduced. Acute cocaine enhanced activity of the CSE and 3-MST in the liver and kidney, respectively. Repeatedly administered cocaine enhanced the whole pool of sulfane sulfur and reduced H2S level simultaneously increasing sulfate content both in the liver and kidney. After repeated cocaine, a significant decrease in ROS was still observed in the liver while in the kidney, despite unchanged ROS content, a marked increase in MDA level was visible. The repeated cocaine decreased 3-MST and increased gamma-GT activities in both organs but reduced GST in the kidney. Our results show that cocaine administered at a relatively low dose shifts Cys metabolism towards the formation of sulfane sulfur compounds which possess antioxidant and redox regulatory properties and are a source of H2S which can support mitochondrial bioenergetics. PMID- 26808534 TI - Effects of Obstacles on the Dynamics of Kinesins, Including Velocity and Run Length, Predicted by a Model of Two Dimensional Motion. AB - Kinesins are molecular motors which walk along microtubules by moving their heads to different binding sites. The motion of kinesin is realized by a conformational change in the structure of the kinesin molecule and by a diffusion of one of its two heads. In this study, a novel model is developed to account for the 2D diffusion of kinesin heads to several neighboring binding sites (near the surface of microtubules). To determine the direction of the next step of a kinesin molecule, this model considers the extension in the neck linkers of kinesin and the dynamic behavior of the coiled-coil structure of the kinesin neck. Also, the mechanical interference between kinesins and obstacles anchored on the microtubules is characterized. The model predicts that both the kinesin velocity and run length (i.e., the walking distance before detaching from the microtubule) are reduced by static obstacles. The run length is decreased more significantly by static obstacles than the velocity. Moreover, our model is able to predict the motion of kinesin when other (several) motors also move along the same microtubule. Furthermore, it suggests that the effect of mechanical interaction/interference between motors is much weaker than the effect of static obstacles. Our newly developed model can be used to address unanswered questions regarding degraded transport caused by the presence of excessive tau proteins on microtubules. PMID- 26808535 TI - Glucose Uptake Activities of Bis (2, 3-Dibromo-4, 5-Dihydroxybenzyl) Ether, a Novel Marine Natural Product from Red Alga Odonthaliacorymbifera with Protein Tyrosine Phosphatase 1B Inhibition, In Vitro and In Vivo. AB - BACKGROUND AND AIMS: Protein tyrosine phosphatase 1B (PTP1B) is a novel therapeutic target for type-2 diabetes, which negatively regulates the insulin signaling transduction. Bis (2, 3-dibromo-4, 5-dihydroxybenzyl) ether (BDDE), a novel bromophenol isolated from the Red Alga, is a novel PTP1B inhibitor. But the anti-diabetic effects are not clear. In the present study, we evaluated the in vitro and in vivo antidiabetic effects of BDDE. METHODS: The insulin-resistant HepG2 cells were used to evaluate the in vitro antidiabetic effects of BDDE. MTT assay was used to determine the safety concentrations in HepG2 cells. Glucose assay kit was used to check glucose uptake after treated with BDDE. Western blotting assay was used to explore the potent mechanisms. The db/db mice were used to evaluate the in vivo antidiabetic effects of BDDE. Body weight, blood glucose, Glycated hemoglobin (HbA1c), lipid profile, and insulin level were checked at the respective time points. Gastrocnemii were dissected and used to analyze the PTP1B and insulin receptor beta (IRbeta) expression. RESULTS: BDDE increased the insulin-resisted glucose uptake in HepG2 cells. BDDE also decreased the expression of PTP1B and activated the substrates and downstream signals in insulin signal pathway, such as IRbeta, insulin receptor substrate-1/2 (IRS1/2), phosphoinositide 3-kinase (PI3K), and protein kinase B (PKB/Akt). In the db/db mice model, BDDE significantly decreased the blood glucose, HbA1c and triglyceride (TG) levels. BDDE also decreased the expression of PTP1B and activated the phosphorylation of IRbeta in gastrocnemii. Moreover, BDDE at high doses downregulated the body weight without affecting food and water intake. CONCLUSION: Our results suggest that BDDE as a new PTP1B inhibitor improves glucose metabolism by stimulating the insulin signaling and could be used in the treatment of type-2 diabetes mellitus. PMID- 26808536 TI - Rational Design of a Carrier Protein for the Production of Recombinant Toxic Peptides in Escherichia coli. AB - Commercial uses of bioactive peptides require low cost, effective methods for their production. We developed a new carrier protein for high yield production of recombinant peptides in Escherichia coli very well suited for the production of toxic peptides like antimicrobial peptides. GKY20, a short antimicrobial peptide derived from the C-terminus of human thrombin, was fused to the C-terminus of Onconase, a small ribonuclease (104 amino acids), which efficiently drove the peptide into inclusion bodies with very high expression levels (about 200-250 mg/L). After purification of the fusion protein by immobilized metal ion affinity chromatography, peptide was obtained by chemical cleavage in diluted acetic acid of an acid labile Asp-Pro sequence with more than 95% efficiency. To improve peptide purification, Onconase was mutated to eliminate all acid labile sequences thus reducing the release of unwanted peptides during the acid cleavage. Mutations were chosen to preserve the differential solubility of Onconase as function of pH, which allows its selective precipitation at neutral pH after the cleavage. The improved carrier allowed the production of 15-18 mg of recombinant peptide per liter of culture with 96-98% purity without the need of further chromatographic steps after the acid cleavage. The antimicrobial activity of the recombinant peptide, with an additional proline at the N-terminus, was tested on Gram-negative and Gram-positive strains and was found to be identical to that measured for synthetic GKY20. This finding suggests that N-terminal proline residue does not change the antimicrobial properties of recombinant (P)GKY20. The improved carrier, which does not contain cysteine and methionine residues, Asp Pro and Asn-Gly sequences, is well suited for the production of peptides using any of the most popular chemical cleavage methods. PMID- 26808537 TI - Reduced Adenosine Uptake and Its Contribution to Signaling that Mediates Profibrotic Activation in Renal Tubular Epithelial Cells: Implication in Diabetic Nephropathy. AB - Altered nucleoside levels may be linked to pathogenic signaling through adenosine receptors. We hypothesized that adenosine dysregulation contributes to fibrosis in diabetic kidney disease. Our findings indicate that high glucose levels and experimental diabetes decreased uptake activity through the equilibrative nucleoside transporter 1 (ENT1) in proximal tubule cells. In addition, a correlation between increased plasma content of adenosine and a marker of renal fibrosis in diabetic rats was evidenced. At the cellular level, exposure of HK2 cells to high glucose, TGF-beta and the general adenosine receptor agonist NECA, induced the expression of profibrotic cell activation markers alpha-SMA and fibronectin. These effects can be avoided by using a selective antagonist of the adenosine A3 receptor subtype in vitro. Furthermore, induction of fibrosis marker alpha-SMA was prevented by the A3 receptor antagonist in diabetic rat kidneys. In conclusion, we evidenced the contribution of purinergic signaling to renal fibrosis in experimental diabetic nephropathy. PMID- 26808538 TI - "Life in Data"--Outcome of a Multi-Disciplinary, Interactive Biobanking Conference Session on Sample Data. AB - INTRODUCTION: Clinical, biodiversity, and environmental biobanks share many data standards, but there is a lack of harmonization on how data are defined and used among biobank fields. This article reports the outcome of an interactive, multidisciplinary session at a meeting of the European, Middle Eastern, and African Society for Biopreservation and Biobanking (ESBB) designed to encourage a 'learning-from-each-other' approach to achieve consensus on data needs and data management across biobank communities. MATERIALS, METHODS, AND RESULTS: The Enviro-Bio and ESBBperanto Working Groups of the ESBB co-organized an interactive session at the 2013 conference (Verona, Italy), presenting data associated with biobanking processes, using examples from across different fields. One-hundred sixty (160) diverse biobank participants were provided electronic voting devices with real-time screen display of responses to questions posed during the session. The importance of data standards and robust data management was recognized across the conference cohort, along with the need to raise awareness about these issues within and across different biobank sectors. DISCUSSION AND CONCLUSION: While interactive sessions require a commitment of time and resources, and must be carefully coordinated for consistency and continuity, they stimulate the audience to be pro-active and direct the course of the session. This effective method was used to gauge opinions about significant topics across different biobanking communities. The votes revealed the need to: (a) educate biobanks in the use of data management tools and standards, and (b) encourage a more cohesive approach for how data and samples are tracked, exchanged, and standardized across biobanking communities. Recommendations for future interactive sessions are presented based on lessons learned. PMID- 26808539 TI - Surface Phosphatidylserine Is Responsible for the Internalization on Microvesicles Derived from Hypoxia-Induced Human Bone Marrow Mesenchymal Stem Cells into Human Endothelial Cells. AB - BACKGROUND: Previous data have proven that microvesicles derived from hypoxia induced mesenchymal stem cells (MSC-MVs) can be internalized into endothelial cells, enhancing their proliferation and vessel structure formation and promoting in vivo angiogenesis. However, there is a paucity of information about how the MSC-MVs are up-taken by endothelial cells. METHODS: MVs were prepared from the supernatants of human bone marrow MSCs that had been exposed to a hypoxic and/or serum-deprivation condition. The incorporation of hypoxia-induced MSC-MVs into human umbilical cord endothelial cells (HUVECs) was observed by flow cytometry and confocal microscopy in the presence or absence of recombinant human Annexin-V (Anx-V) and antibodies against human CD29 and CD44. Further, small interfering RNA (siRNA) targeted at Anx-V and PSR was delivered into HUVECs, or HUVECs were treated with a monoclonal antibody against phosphatidylserine receptor (PSR) and the cellular internalization of MVs was re-assessed. RESULTS: The addition of exogenous Anx-V could inhibit the uptake of MVs isolated from hypoxia-induced stem cells by HUVECs in a dose- and time-dependent manner, while the anti-CD29 and CD44 antibodies had no effect on the internalization process. The suppression was neither observed in Anx-V siRNA-transfected HUVECs, however, addition of anti PSR antibody and PSR siRNA-transfected HUVECs greatly blocked the incorporation of MVs isolated from hypoxia-induced stem cells into HUVECs. CONCLUSION: PS on the MVs isolated from hypoxia-induced stem cells is the critical molecule in the uptake by HUVECs. PMID- 26808540 TI - Pro-Inflammatory Markers in Relation to Cardiovascular Disease in HIV Infection. A Systematic Review. AB - BACKGROUND: In the past years many inflammatory markers have been studied in association with clinically manifest cardiovascular disease (CVD) and carotid intima-media thickness (CIMT) in HIV-infected patients, to obtain insights in the increased cardiovascular risk observed in HIV infection. This systematic review provides an oversight of the current knowledge. METHODS: A search was performed in PubMed, Embase and Cochrane in July 2014, identifying all articles from 1996 onwards addressing the relation between inflammatory markers and CVD or CIMT in HIV-positive adults. Two authors, using predefined criteria, independently conducted the selection of articles, critical appraisal and extraction of the data. Analysis was focused on the immune markers that were most frequently assessed. The review protocol was registered in the PROSPERO database at 11 July 2014 (registration number CRD42014010516). This review was performed according to the PRISMA guideline. FINDINGS: Forty articles were selected; eight addressing cardiovascular disease (CVD) and thirty-two addressing CIMT. C-reactive protein (CRP), interleukin-6 (IL-6) and d-dimer were assessed most frequently in relation to the occurrence of CVD; in four out of eight studies. All three markers were positively related to CVD in three out of four studies. Studies addressing CIMT were too heterogeneous with respect to patient populations, inflammatory markers, CIMT measurement protocols and statistical methods to allow for a formal meta analysis to obtain summary statistics. CRP, IL-6 and soluble vascular cell adhesion molecule (sVCAM-1) were the most studied markers in relation to CIMT. None of the inflammatory markers showed an association with CIMT. INTERPRETATION: This review showed a relation between some inflammatory markers and CVD, however, no consistent relation is observed for CIMT. Statistical approaches that yields effect estimates and standardized CIMT protocols should be chosen. Further research should focus on prospective studies and a selected set of inflammatory markers. PMID- 26808541 TI - Development and Two-Year Follow-Up Evaluation of a Training Workshop for the Large Preventive Positive Psychology Happy Family Kitchen Project in Hong Kong. AB - Evidence-based practice and capacity-building approaches are essential for large scale health promotion interventions. However, there are few models in the literature to guide and evaluate training of social service workers in community settings. This paper presents the development and evaluation of the "train-the trainer" workshop (TTT) for the first large scale, community-based, family intervention projects, entitled "Happy Family Kitchen Project" (HFK) under the FAMILY project, a Hong Kong Jockey Club Initiative for a Harmonious Society. The workshop aimed to enhance social workers' competence and performance in applying positive psychology constructs in their family interventions under HFK to improve family well-being of the community they served. The two-day TTT was developed and implemented by a multidisciplinary team in partnership with community agencies to 50 social workers (64% women). It focused on the enhancement of knowledge, attitude, and practice of five specific positive psychology themes, which were the basis for the subsequent development of the 23 family interventions for 1419 participants. Acceptability and applicability were enhanced by completing a needs assessment prior to the training. The TTT was evaluated by trainees' reactions to the training content and design, changes in learners (trainees) and benefits to the service organizations. Focus group interviews to evaluate the workshop at three months after the training, and questionnaire survey at pre-training, immediately after, six months, one year and two years after training were conducted. There were statistically significant increases with large to moderate effect size in perceived knowledge, self-efficacy and practice after training, which sustained to 2-year follow-up. Furthermore, there were statistically significant improvements in family communication and well-being of the participants in the HFK interventions they implemented after training. This paper offers a practical example of development, implementation and model-based evaluation of training programs, which may be helpful to others seeking to develop such programs in diverse communities. PMID- 26808542 TI - Three-Dimensional Quantitative Morphometric Analysis (QMA) for In Situ Joint and Tissue Assessment of Osteoarthritis in a Preclinical Rabbit Disease Model. AB - This work utilises advances in multi-tissue imaging, and incorporates new metrics which define in situ joint changes and individual tissue changes in osteoarthritis (OA). The aims are to (1) demonstrate a protocol for processing intact animal joints for microCT to visualise relevant joint, bone and cartilage structures for understanding OA in a preclinical rabbit model, and (2) introduce a comprehensive three-dimensional (3D) quantitative morphometric analysis (QMA), including an assessment of reproducibility. Sixteen rabbit joints with and without transection of the anterior cruciate ligament were scanned with microCT and contrast agents, and processed for histology. Semi-quantitative evaluation was performed on matching two-dimensional (2D) histology and microCT images. Subsequently, 3D QMA was performed; including measures of cartilage, subchondral cortical and epiphyseal bone, and novel tibio-femoral joint metrics. Reproducibility of the QMA was tested on seven additional joints. A significant correlation was observed in cartilage thickness from matching histology-microCT pairs. The lateral compartment of operated joints had larger joint space width, thicker femoral cartilage and reduced bone volume, while osteophytes could be detected quantitatively. Measures between the in situ tibia and femur indicated an altered loading scenario. High measurement reproducibility was observed for all new parameters; with ICC ranging from 0.754 to 0.998. In conclusion, this study provides a novel 3D QMA to quantify macro and micro tissue measures in the joint of a rabbit OA model. New metrics were established consisting of: an angle to quantitatively measure osteophytes (sigma), an angle to indicate erosion between the lateral and medial femoral condyles (rho), a vector defining altered angulation (lambda, alpha, beta, gamma) and a twist angle (tau) measuring instability and tissue degeneration between the femur and tibia, a length measure of joint space width (JSW), and a slope and intercept (m, Chi) of joint contact to demonstrate altered loading with disease progression, as well as traditional bone and cartilage and histo-morphometry measures. We demonstrate correlation of microCT and histology, sensitive discrimination of OA change and robust reproducibility. PMID- 26808543 TI - Treatment Failure after Multiple Courses of Triclabendazole among Patients with Fascioliasis in Cusco, Peru: A Case Series. AB - Triclabendazole is reported to be highly effective in treatment of human fascioliasis. We present 7 of 19 selected cases of human fascioliasis referred to our center in the Cusco region of Peru that failed to respond to triclabendazole. These were mostly symptomatic adults of both sexes that continued passing Fasciola eggs in the stool despite multiple treatments with 2 doses of triclabendazole at 10 mg/kg per dose. We documented the presence of eggs by rapid sedimentation and Kato Katz tests after each treatment course. We found that repeated triclabendazole courses were not effective against fascioliasis in this group of people. These findings suggest that resistance to triclabendazole may be an emerging problem in the Andes. PMID- 26808544 TI - A Glutathione-Nrf2-Thioredoxin Cross-Talk Ensures Keratinocyte Survival and Efficient Wound Repair. AB - The tripeptide glutathione is the most abundant cellular antioxidant with high medical relevance, and it is also required as a co-factor for various enzymes involved in the detoxification of reactive oxygen species and toxic compounds. However, its cell-type specific functions and its interaction with other cytoprotective molecules are largely unknown. Using a combination of mouse genetics, functional cell biology and pharmacology, we unraveled the function of glutathione in keratinocytes and its cross-talk with other antioxidant defense systems. Mice with keratinocyte-specific deficiency in glutamate cysteine ligase, which catalyzes the rate-limiting step in glutathione biosynthesis, showed a strong reduction in keratinocyte viability in vitro and in the skin in vivo. The cells died predominantly by apoptosis, but also showed features of ferroptosis and necroptosis. The increased cell death was associated with increased levels of reactive oxygen and nitrogen species, which caused DNA and mitochondrial damage. However, epidermal architecture, and even healing of excisional skin wounds were only mildly affected in the mutant mice. The cytoprotective transcription factor Nrf2 was strongly activated in glutathione-deficient keratinocytes, but additional loss of Nrf2 did not aggravate the phenotype, demonstrating that the cytoprotective effect of Nrf2 is glutathione dependent. However, we show that deficiency in glutathione biosynthesis is efficiently compensated in keratinocytes by the cysteine/cystine and thioredoxin systems. Therefore, our study highlights a remarkable antioxidant capacity of the epidermis that ensures skin integrity and efficient wound healing. PMID- 26808545 TI - Structure of the Intermediate Filament-Binding Region of Desmoplakin. AB - Desmoplakin (DP) is a cytoskeletal linker protein that connects the desmosomal cadherin/plakoglobin/plakophilin complex to intermediate filaments (IFs). The C terminal region of DP (DPCT) mediates IF binding, and contains three plakin repeat domains (PRDs), termed PRD-A, PRD-B and PRD-C. Previous crystal structures of PRDs B and C revealed that each is formed by 4.5 copies of a plakin repeat (PR) and has a conserved positively charged groove on its surface. Although PRDs A and B are linked by just four amino acids, B and C are separated by a 154 residue flexible linker, which has hindered crystallographic analysis of the full DPCT. Here we present the crystal structure of a DPCT fragment spanning PRDs A and B, and elucidate the overall architecture of DPCT by small angle X-ray scattering (SAXS) analysis. The structure of PRD-A is similar to that of PRD-B, and the two domains are arranged in a quasi-linear arrangement, and separated by a 4 amino acid linker. Analysis of the B-C linker region using secondary structure prediction and the crystal structure of a homologous linker from the cytolinker periplakin suggests that the N-terminal ~100 amino acids of the linker form two PR-like motifs. SAXS analysis of DPCT indicates an elongated but non linear shape with Rg = 51.5 A and Dmax = 178 A. These data provide the first structural insights into an IF binding protein containing multiple PRDs and provide a foundation for studying the molecular basis of DP-IF interactions. PMID- 26808546 TI - A Novel Biomarker Panel Examining Response to Gemcitabine with or without Erlotinib for Pancreatic Cancer Therapy in NCIC Clinical Trials Group PA.3. AB - PURPOSE: NCIC Clinical Trials Group PA.3 was a randomized control trial that demonstrated improved overall survival (OS) in patients receiving erlotinib in addition to gemcitabine for locally advanced or metastatic pancreatic cancer. Prior to therapy, patients had plasma samples drawn for future study. We sought to identify biomarkers within these samples. EXPERIMENTAL DESIGN: Using the proximity ligation assay (PLA), a probe panel was built from commercially available antibodies for 35 key proteins selected from a global genetic analysis of pancreatic cancers, and used to quantify protein levels in 20 uL of patient plasma. To determine if any of these proteins levels independently associated with OS, univariate and mulitbaraible Cox models were used. In addition, we examined the associations between biomarker expression and disease stage at diagnosis using Fisher's exact test. The correlation between Erlotinib sensitivity and each biomarkers was assessed using a test of interaction between treatment and biomarker. RESULTS AND CONCLUSION: Of the 569 eligible patients, 480 had samples available for study. Samples were randomly allocated into training (251) and validation sets (229). Among all patients, elevated levels of interleukin-8 (IL-8), carcinoembryonic antigen (CEA), hypoxia-inducible factor 1 alpha (HIF-1 alpha), and interleukin-6 were independently associated with lower OS, while IL-8, CEA, platelet-derived growth factor receptor alpha and mucin-1 were associated with metastatic disease. Patients with elevated levels of receptor tyrosine-protein kinase erbB-2 (HER2) expression had improved OS when treated with erlotinib compared to placebo. In conclusion, PLA is a powerful tool for identifying biomarkers from archived, small volume serum samples. These data may be useful to stratify patient outcomes regardless of therapeutic intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT00040183. PMID- 26808547 TI - Factors Associated with Ever Being HIV-Tested in Zimbabwe: An Extended Analysis of the Zimbabwe Demographic and Health Survey (2010-2011). AB - INTRODUCTION: Zimbabwe has a high human immunodeficiency virus (HIV) burden. It is therefore important to scale up HIV-testing and counseling (HTC) as a gateway to HIV prevention, treatment and care. OBJECTIVE: To determine factors associated with being HIV-tested among adult men and women in Zimbabwe. METHODS: Secondary analysis was done using data from 7,313 women and 6,584 men who completed interviewer-administered questionnaires and provided blood specimens for HIV testing during the Zimbabwe Demographic and Health Survey (ZDHS) 2010-11. Factors associated with ever being HIV-tested were determined using multivariate logistic regression. RESULTS: HIV-testing was higher among women compared to men (61% versus 39%). HIV-infected respondents were more likely to be tested compared to those who were HIV-negative for both men [adjusted odds ratio (AOR) = 1.53; 95% confidence interval (CI) (1.27-1.84)] and women [AOR = 1.42; 95% CI (1.20-1.69)]. However, only 55% and 74% of these HIV-infected men and women respectively had ever been tested. Among women, visiting antenatal care (ANC) [AOR = 5.48, 95% CI (4.08-7.36)] was the most significant predictor of being tested whilst a novel finding for men was higher odds of testing among those reporting a sexually transmitted infection (STI) in the past 12 months [AOR = 1.86, 95%CI (1.26 2.74)]. Among men, the odds of ever being tested increased with age >= 20 years, particularly those 45-49 years [AOR = 4.21; 95% CI (2.74-6.48)] whilst for women testing was highest among those aged 25-29 years [AOR = 2.01; 95% CI (1.63 2.48)]. Other significant factors for both sexes were increasing education level, higher wealth status and currently/formerly being in union. CONCLUSIONS: There remains a high proportion of undiagnosed HIV-infected persons and hence there is a need for innovative strategies aimed at increasing HIV-testing, particularly for men and in lower-income and lower-educated populations. Promotion of STI services can be an important gateway for testing more men whilst ANC still remains an important option for HIV-testing among pregnant women. PMID- 26808548 TI - The Toll-Like Receptor 4 (TLR4) Variant rs2149356 and Risk of Gout in European and Polynesian Sample Sets. AB - Deposition of crystallized monosodium urate (MSU) in joints as a result of hyperuricemia is a central risk factor for gout. However other factors must exist that control the progression from hyperuricaemia to gout. A previous genetic association study has implicated the toll-like receptor 4 (TLR4) which activates the NLRP3 inflammasome via the nuclear factor-kappaB signaling pathway upon stimulation by MSU crystals. The T-allele of single nucleotide polymorphism rs2149356 in TLR4 is a risk factor associated with gout in a Chinese study. Our aim was to replicate this observation in participants of European and New Zealand Polynesian (Maori and Pacific) ancestry. A total of 2250 clinically-ascertained prevalent gout cases and 13925 controls were used. Non-clinically-ascertained incident gout cases and controls from the Health Professional Follow-up (HPFS) and Nurses Health Studies (NHS) were also used. Genotypes were derived from genome-wide genotype data or directly obtained using Taqman. Logistic regression analysis was done including age, sex, diuretic exposure and ancestry as covariates as appropriate. The T-allele increased the risk of gout in the clinically-ascertained European samples (OR = 1.12, P = 0.012) and decreased the risk of gout in Polynesians (OR = 0.80, P = 0.011). There was no evidence for association in the HPFS or NHS sample sets. In conclusion TLR4 SNP rs2143956 associates with gout risk in prevalent clinically-ascertained gout in Europeans, in a direction consistent with previously published results in Han Chinese. However, with an opposite direction of association in Polynesians and no evidence for association in a non-clinically-ascertained incident gout cohort this variant should be analysed in other international gout genetic data sets to determine if there is genuine evidence for association. PMID- 26808549 TI - Histone demethylase KDM2B regulates lineage commitment in normal and malignant hematopoiesis. AB - The development of the hematopoietic system is a dynamic process that is controlled by the interplay between transcriptional and epigenetic networks to determine cellular identity. These networks are critical for lineage specification and are frequently dysregulated in leukemias. Here, we identified histone demethylase KDM2B as a critical regulator of definitive hematopoiesis and lineage commitment of murine hematopoietic stem and progenitor cells (HSPCs). RNA sequencing of Kdm2b-null HSPCs and genome-wide ChIP studies in human leukemias revealed that KDM2B cooperates with polycomb and trithorax complexes to regulate differentiation, lineage choice, cytokine signaling, and cell cycle. Furthermore, we demonstrated that KDM2B exhibits a dichotomous role in hematopoietic malignancies. Specifically, we determined that KDM2B maintains lymphoid leukemias, but restrains RAS-driven myeloid transformation. Our study reveals that KDM2B is an important mediator of hematopoietic cell development and has opposing roles in tumor progression that are dependent on cellular context. PMID- 26808551 TI - Continuum and atomistic description of excess electrons in TiO2. AB - The modelling of an excess electron in a semiconductor in a prototypical dye sensitised solar cell is carried out using two complementary approaches: atomistic simulation of the TiO2 nanoparticle surface is complemented by a dielectric continuum model of the solvent-semiconductor interface. The two methods are employed to characterise the bound (excitonic) states formed by the interaction of the electron in the semiconductor with a positive charge opposite the interface. Density-functional theory (DFT) calculations show that the excess electron in TiO2 in the presence of a counterion is not fully localised but extends laterally over a large region, larger than system sizes accessible to DFT calculations. The numerical description of the excess electron at the semiconductor-electrolyte interface based on the continuum model shows that the exciton is also delocalised over a large area: the exciton radius can have values from tens to hundreds of Angstroms, depending on the nature of the semiconductor (characterised by the dielectric constant and the electron effective mass in our model). PMID- 26808550 TI - Do the CONSORT and STRICTA Checklists Improve the Reporting Quality of Acupuncture and Moxibustion Randomized Controlled Trials Published in Chinese Journals? A Systematic Review and Analysis of Trends. AB - BACKGROUND: We investigated whether there had been an improvement in the quality of reporting for randomised controlled trials of acupuncture and moxibustion published in Chinese journals. We compared the compliance rate for the quality of reporting following the publication of both the STRICTA and CONSORT recommendations in China. METHODS: Four Chinese databases were searched for RCTs of acupuncture from January 1978 through to December 2012. The CONSORT and STRICTA checklists were used to assess the quality of reporting. Data were collected using a standardised form. All included RCTs were divided into three distinct time periods based on the time that CONSORT and STRICTA were introduced in China, respectively. Pearson's chi2 test and/or Fisher's exact test were used to assess differences in reporting among three groups. PRINCIPAL FINDINGS: A total of 1978 RCTs were identified. Although the percentage of all the items has increased over time with the introduction of CONSORT and STRICTA in China, the actual compliance in several important methodological components, including sample size calculation (0% vs. 0% vs. 1.2%, for pre-CONSORT and pre-STRICTA, post-CONSORT but pre-STRICTA, and post-CONSORT and post-STRICTA, respectively), randomisation sequence generation (1.4% vs. 15% vs. 26.3%) and implementation (0% vs. 0% vs. 1.3%), allocation concealment (0% vs. 1.4% vs. 4.9%), and blinding (0% vs. 5.7% vs. 9.1%), remains low. Moreover, no RCTs have reported the setting and context of treatment and no descriptions of the participating acupuncturists have been provided thus far. CONCLUSIONS: Overall, the quality of the reporting of RCTs of acupuncture and moxibustion published in Chinese journals has improved since CONSORT and STRICTA were introduced in China, though the actual compliance rate of some important items were still low as of 2012. In the future, Chinese journals should enhance the adoption of the CONSORT and STRICTA statement to improve the reporting quality of the RCTs of acupuncture and moxibustion and to ensure the truth and reliability of the conclusions. PMID- 26808553 TI - Vestibular Migraine: Vestibular Symptom May Identify Different Subgroups. AB - OBJECTIVE: The objective of this study was to evaluate patients with vestibular migraine and analyze whether different vestibular symptoms were able to discriminate different subgroups. PATIENTS: Eighty-three patients (73 women, mean age 42 yr) who fulfilled the criteria for vestibular migraine were selected. INTERVENTION: Participants were divided into two groups according to their vestibular symptoms: spontaneous vertigo (SV) or triggered vertigo (TV). In each group, migraine subtype (migraine with aura and migraine without aura) was further analyzed. RESULTS: The SV group comprised 40 patients (35 women, mean age 42.6 yr) of which 26 had migraine with aura. The TV group comprised 43 patients (38 women, mean age 41.3 yr) of which 34 had migraine without aura. A significant difference in the presence of spontaneous vertigo was noted, proving more frequent in the migraine with aura group, whereas TV was more frequent in the migraine without aura group (chi(2) test, p < 0.0001). CONCLUSION: Spontaneous rotatory vertigo was more frequent in migraine with aura, whereas triggered nonrotatory vertigo was more frequent in migraine without aura. This finding suggests a broad spectrum of clinical symptomatology in vestibular migraine patients. All of these patients are classified as vestibular migraine but they may represent two extremes of a disease spectrum. PMID- 26808552 TI - Adolescent Pregnancy and Attained Height among Black South African Girls: Matched Pair Prospective Study. AB - IMPORTANCE: The impact of adolescent pregnancy on offspring birth outcomes has been widely studied, but less is known about its impact on the growth of the young mother herself. OBJECTIVE: To determine the association between adolescent pregnancy and attained height. DESIGN: Prospective birth cohort study. SETTING: Cohort members followed from birth to age 20 y in Soweto, South Africa. PARTICIPANT: From among 840 Black females with sufficient data, we identified 54 matched pairs, in which a girl who became pregnant before the age of 17 years was matched with a girl who did not have a pregnancy by age 20 y. Pairs were matched on age at menarche and height-for-age z scores in the year before the case became pregnant (mean 15.0 y). MAIN OUTCOME MEASURES: The two groups were compared with respect to attained height, measured at mean age 18.5 y. RESULTS: Mean age at conception was 15.9 years (range: 13.7 to 16.9 y). Mean height at matching was 159.4 cm in the adolescent pregnancy group and 159.3 cm in the comparison group (p = 0.3). Mean attained height was 160.4 cm in the adolescent pregnancy group and 160.3 cm in the comparison group (p = 0.7). CONCLUSIONS: Among Black females in Soweto, South Africa, adolescent pregnancy was not associated with attained height. PMID- 26808554 TI - Sensorineural Hearing Loss in Cholesteatoma. AB - OBJECTIVE: To determine whether middle ear cholesteatoma is associated with, sensorineural hearing loss, and whether patient age, cholesteatoma growth pattern, or, air bone gap size contribute to inner ear impairment. STUDY DESIGN: Cross-sectional comparative. SETTING: A tertiary hospital. PATIENTS: The subjects were 115 patients with middle ear cholesteatoma in one ear, and normal video otoscopy in the contralateral ear (CLE). INTERVENTIONS: Otoendoscopy, pure-tone audiometry. MAIN OUTCOME MEASURES: Bone conduction (BC) threshold differences between the normal CLE and the cholesteatoma ear. Comparisons of these differences between different cholesteatoma growth patterns. Correlation between the air bone gap size in the ear with cholesteatoma and the difference in bone conduction thresholds between both ears. RESULTS: The cholesteatoma ear was associated with greater BC thresholds than the CLE. With regard to different cholesteatoma growth patterns, the differences between associated BC thresholds were also significant in all groups at all frequencies, with the exception of the two routes of cholesteatoma group at 500 Hz. Comparing BC threshold differences, they were greater in the adult group at 500 Hz. The correlation between the air bone gap media in the ear with cholesteatoma and the difference in bone conduction thresholds between both ears was direct and moderate. CONCLUSION: Cholesteatoma was associated with greater BC thresholds at all frequencies tested. The differences were independent of cholesteatoma growth patterns. As bigger the air bone gap in the ear with cholesteatoma, greater the inner ear damage. PMID- 26808555 TI - Sanna Classification and Prognosis of Cholesteatoma of the Petrous Part of the Temporal Bone: A Retrospective Series of 81 Patients. AB - OBJECTIVE: To determine how classification of petrous bone cholesteatomas (PBCs) using the 5-point Sanna classification can predict major structural involvement, facial nerve outcomes, hearing outcomes, postoperative complications, and disease recurrence. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center in Bergamo, Italy. PATIENTS: Eighty-one sequential patients with radiologic and surgically confirmed diagnoses of PBC treated at a single tertiary referral center during a 20-year period. MAIN OUTCOME MEASURES: Major structural involvement, facial nerve outcomes, hearing outcomes, postoperative cerebrospinal fluid leak, and disease recurrence were evaluated on the basis of Sanna classification. RESULTS: Using the Sanna classification, 70% (57) were supralabyrinthine, 12% (10) infralabyrinthine, 7% (6) infralabyrinthine-apical, 5% (4) apical, and 5% (4) massive. Massive classification was statistically significantly associated with cochlear involvement (p = 0.009) and internal auditory canal involvement (p = 0.02). The infralabyrinthine-apical class was associated with carotid canal involvement (p = 0.03). Facial nerve interruption was observed in 35% of patients and most frequently in the apical group (75%). Neither hearing nor facial nerve outcomes were associated with Sanna classification. House-Brackmann score improved or was maintained postoperatively in 89% of patients. CONCLUSION: The Sanna classification provides anatomic detail on location of PBCs and is predictive of IAC, cochlear, and carotid artery involvement. However, classification systems for this rare condition continue to pose a challenge in being able to accurately predict facial nerve and hearing outcomes in surgical obliteration of PBC. PMID- 26808556 TI - Isolated Vestibular Suppression Impairment With Vestibular Migraine: A Phenotypic CANVAS Variant. AB - HYPOTHESIS: Cerebellar Ataxia with Neuropathy and Vestibular Areflexia (CANVAS) is likely to have a genetic basis. We describe the unique eye movement features of a possible phenotypic CANVAS variant. BACKGROUND: The patient comes from a large CANVAS kindred (four out of nine siblings) and has sensory neuropathy, cerebellar eye signs, and vestibular migraine (VM), but otherwise normal vestibular function. METHODS: We recorded eye and head movements using the gold standard scleral search coil technique: in the patient, a close relative with mild sensory neuropathy, and a normal control. RESULTS: At >= 0.8 Hz vestibulo ocular reflex suppression (VORS) was significantly smaller in the patient. At 1 Hz, the patient's VORS was almost two times worse than the control, and five times worse at 1.6 Hz. The patient's VORS deficiency was observed with the naked eye as an inability to keep the eye stationary during imposed sinusoidal head rotation at ~ 1 Hz. At <= 0.8 Hz the patient had 10 to 20% lower smooth pursuit function compared with both the patient-relative and control subjects. This difference was difficult to detect by the naked eye. Saccadic oculomotor and vestibular function was normal. CONCLUSION: We propose that impaired VORS and VM are because of similar, but distinct, consequences of selective partial cerebellar dysfunction. The patient's VORS data are consistent with a CANVAS neuropathological study showing selective degeneration of the dorsal vermis of the cerebellum, a region thought to be important for VORS. Taken together our findings suggest the patient is a CANVAS variant. We hypothesise VORS impairment is part of CANVAS, but not revealed because of vestibular loss. PMID- 26808557 TI - The Use of Temporoparietal Fascial Flap to Eliminate Wound Breakdown in Subtotal Petrosectomy for Chronic Discharging Ears. AB - OBJECTIVE: To find out if the use of the vascularized temporo-parietal fascial flap (TPFF) reduces postoperative infection or wound breakdown in subtotal petrosectomy for chronic discharging ears. PATIENTS: A retrospective review on 26 subtotal petrosectomies with blind pit closures on chronic discharging ears performed by a single surgeon between 2000 and 2015 was performed. All patients had a minimum follow-up period of 6 months. INTERVENTION: Eleven mastoid cavities were obliterated with abdominal fat, and 15 cavities were obliterated with TPFF. There was no concomitant cochlear implant or middle ear implant. MAIN OUTCOME MEASURE(S): All postoperative wound infections or delay in wound healing were recorded into a database. The complication rates of the fat obliteration group were compared using Fisher's exact test with those for the TPFF obliteration group. RESULTS: In the fat obliteration group, 4 out of 11 patients had documented postoperative complications. Three had wound breakdown with exposure of the fat that required revision surgery. Another patient had postauricular abscess without the wound actually broken down. On the other hand, all the ears in the TPFF obliteration group (100%) were completely free of wound infection, wound breakdown, or any complication. The difference between the two groups was statistically significant (p = 0.022). CONCLUSION: Many authors have encountered postoperative infection or wound breakdown in subtotal petrosectomy with fat obliteration in the treatment of chronic otitis media. Using a richly vascularized temporo-temporal fascial flap to protect the blind pit closure in such patients reduces postoperative infection and wound breakdown. PMID- 26808558 TI - Meniett Therapy for Meniere's Disease: An Updated Meta-analysis. AB - OBJECTIVE: To re-evaluate the efficacy of Meniett therapy for the treatment of Meniere's disease (MD). DATA SOURCES: PubMed, Embase, Cochrane Library, Clinicaltrials.gov, ChiCTR, and the CNKI database were searched for articles in English and Chinese published before August 31, 2015. STUDY SELECTION: Included in this meta-analysis were studies that dealt with outcomes of Meniett therapy for the treatment of MD, including randomized controlled clinical trials, case control studies, and prospective or retrospective cohort studies, with sample sizes of >= 10 subjects. DATA EXTRACTION: Keywords included endolymphatic hydrops, Meniere's disease, pressure, Meniett, and transtympanic micropressure treatment. DATA SYNTHESIS: Fourteen studies were included, involving a total of 345 MD patients. Data were analyzed using the Meta package in R. Dichotomous outcomes were expressed as risk ratios with 95% confidence intervals, and weighted mean differences with 95% confidence intervals were used to present continuous outcomes. Heterogeneity of the included studies was quantitatively assessed by chi(2) and I tests. Fixed-effects models were used for I(2) <50%; otherwise, random-effects models were used. Funnel plots were constructed to test the publication bias. CONCLUSION: This study showed that Meniett therapy may prevent vertigo attacks and substantially reduce its frequency in MD patients. It may also alleviate the functional deficit. The impact of Meniett therapy on hearing remains uncertain. The optimal effect might maintain for approximately 18 months. This meta-analysis suggested that Meniett therapy may be a useful second line therapy in the treatment of MD. PMID- 26808559 TI - Cloning and Expression of Phytase appA Gene from Shigella sp. CD2 in Pichia pastoris and Comparison of Properties with Recombinant Enzyme Expressed in E. coli. AB - The phytase gene appAS was isolated from Shigella sp. CD2 genomic library. The 3.8 kb DNA fragment contained 1299 bp open reading frame encoding 432 amino acid protein (AppAS) with 22 amino acid signal peptide at N-terminal and three sites of N-glycosylation. AppAS contained the active site RHGXRXP and HDTN sequence motifs, which are conserved among histidine acid phosphatases. It showed maximum identity with phytase AppA of Escherichia coli and Citrobacter braakii. The appAS was expressed in Pichia pastoris and E. coli to produce recombinant phytase rAppAP and rAppAE, respectively. Purified glycosylated rAppAP and nonglycosylated rAppAE had specific activity of 967 and 2982 U mg(-1), respectively. Both had pH optima of 5.5 and temperature optima of 60 degrees C. Compared with rAppAE, rAppAP was 13 and 17% less active at pH 3.5 and 7.5 and 11 and 18% less active at temperature 37 and 50 degrees C, respectively; however, it was more active at higher incubation temperatures. Thermotolerance of rAppAP was 33% greater at 60 degrees C and 24% greater at 70 degrees C, when compared with rAppAE. Both the recombinant enzymes showed high specificity to phytate and resistance to trypsin. To our knowledge, this is the first report on cloning and expression of phytase from Shigella sp. PMID- 26808561 TI - Determinants of Heterosexual Adolescents Having Sex with Female Sex Workers in Singapore. AB - OBJECTIVES: We assessed the proportion of and socio-ecological factors associated with ever having had sex with female sex workers (FSWs) among heterosexual adolescents. We also described the characteristics of the adolescents who reported inconsistent condom use with FSWs. METHODS: This is a cross-sectional study (response rate: 73%) of 300 heterosexually active male adolescents of 16 to 19 years attending a national STI clinic in Singapore between 2009 and 2014. We assessed the ecological factors (individual, parental, peer, school and medial influences) and sexual risk behaviors using a self-reported questionnaire. Poisson regression was used to obtain the adjusted prevalence ratios (aPR) and confidence intervals (CI). RESULTS: The proportion of heterosexual male adolescents who had ever had sex with FSWs was 39%. Multivariate analysis showed that significant factors associated with ever having had sex with FSWs were sex initiation before 16 years old (aPR 1.79 CI: 1.30-2.46), never had a sexually active girlfriend (aPR 1.75 CI 1.28-2.38), reported lower self-esteem score (aPR 0.96 CI: 0.93-0.98), higher rebelliousness score (aPR 1.03 CI: 1.00-1.07) and more frequent viewing of pornography (aPR 1.47 CI: 1.04-2.09). Lifetime inconsistent condom use with FSWs was 30%. CONCLUSIONS: A significant proportion of heterosexual male adolescents attending the public STI clinic had ever had sex with FSWs. A targeted intervention that addresses different levels of influence to this behavior is needed. This is even more so because a considerable proportion of adolescents reported inconsistent condom use with FSWs, who may serve as a bridge of STI transmission to the community. National surveys on adolescent health should include the assessment of frequency of commercial sex visits and condom use with FSWs for long-term monitoring and surveillance. PMID- 26808560 TI - Leveraging Genomic Annotations and Pleiotropic Enrichment for Improved Replication Rates in Schizophrenia GWAS. AB - Most of the genetic architecture of schizophrenia (SCZ) has not yet been identified. Here, we apply a novel statistical algorithm called Covariate Modulated Mixture Modeling (CM3), which incorporates auxiliary information (heterozygosity, total linkage disequilibrium, genomic annotations, pleiotropy) for each single nucleotide polymorphism (SNP) to enable more accurate estimation of replication probabilities, conditional on the observed test statistic ("z score") of the SNP. We use a multiple logistic regression on z-scores to combine information from auxiliary information to derive a "relative enrichment score" for each SNP. For each stratum of these relative enrichment scores, we obtain nonparametric estimates of posterior expected test statistics and replication probabilities as a function of discovery z-scores, using a resampling-based approach that repeatedly and randomly partitions meta-analysis sub-studies into training and replication samples. We fit a scale mixture of two Gaussians model to each stratum, obtaining parameter estimates that minimize the sum of squared differences of the scale-mixture model with the stratified nonparametric estimates. We apply this approach to the recent genome-wide association study (GWAS) of SCZ (n = 82,315), obtaining a good fit between the model-based and observed effect sizes and replication probabilities. We observed that SNPs with low enrichment scores replicate with a lower probability than SNPs with high enrichment scores even when both they are genome-wide significant (p < 5x10-8). There were 693 and 219 independent loci with model-based replication rates >=80% and >=90%, respectively. Compared to analyses not incorporating relative enrichment scores, CM3 increased out-of-sample yield for SNPs that replicate at a given rate. This demonstrates that replication probabilities can be more accurately estimated using prior enrichment information with CM3. PMID- 26808562 TI - Public Pensions as the Great Equalizer? Decomposition of Old-Age Income Inequality in South Korea, 1998-2010. AB - This study examines the redistributive effects of public pensions on old-age income inequality, testing whether public pensions function as the "great equalizer." Unlike the well-known alleviating effect of public pensions on old age poverty, the effects of public pensions on old-age income inequality more generally have been less examined, particularly outside Western countries. Using repeated cross-sectional data of elderly Koreans between 1998 and 2010, we applied Gini coefficient decomposition to measure the impact of various income sources on old-age inequality, particularly focusing on public pensions. Our findings show that, contrary to expectations, public pension benefits have inequality-intensifying effects on old-age income in Korea, even countervailing the alleviating effects of public assistance. This rather surprising result is due to the specific institutional context of the Korean public pension system and suggests that the "structuring" of welfare policies could be as important as their expansion for the elderly, particularly for developing welfare states. PMID- 26808563 TI - Correction: The Association between Continuity of Care and All-Cause Mortality in Patients with Newly Diagnosed Obstructive Pulmonary Disease: A Population-Based Retrospective Cohort Study, 2005-2012. PMID- 26808564 TI - TCR alphabeta and CD19-depleted haploidentical stem cell transplant with reduced intensity conditioning for Hoyeraal-Hreidarsson syndrome with RTEL1 mutation. PMID- 26808565 TI - Consideration of noninherited maternal Ags as permissible HLA mismatches in cord blood donor selection. AB - In cord blood (CB) transplantation, virtual 6/6 HLA matches, whereby the donor recipient mismatch is identical to the CB noninherited maternal Ag (NIMA), have similar outcomes to inherited 6/6 matches. In the UK-British Bone Marrow Registry (BBMR), 4707 of the total 21 020 CB donors have the NIMA defined. Retrospective searches of these donors, for 1-3 NIMA matches, identified a virtual 6/6 match for 31.4% of 274 European Caucasoid (EC) and 25.4% of 67 other ethnicity (OE) patients. Patients weighing ?50 kg were also evaluated for a single graft with adequate cell dose. In 125 EC patients, 6/6 HLA matches were identified for 24.0% and virtual 6/6 matches were identified for a further 21.6%. The remaining EC patients had a 5/6 (30.4%) or a 4/6 (22.4%) match. In OE patients, 6/6 HLA matches were identified for 9.3% and virtual 6/6 matches were identified for a further 18.7%. The remaining OE patients had a 5/6 (30.2%) or a 4/6 (37.2%) match. Searches were also performed using the 26 735 Bone Marrow Donors Worldwide CB with defined NIMA and yielded comparable increases. Considering NIMA as permissible mismatches in donor selection therefore increased the availability of a 6/6 match in this cohort. PMID- 26808566 TI - Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR. AB - Although allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling donor (MSD) is a potentially curative post-remission treatment for adults with acute myeloid leukemia (AML) in their first CR, transplant-related morbidity and mortality remains a major drawback. We retrospectively compared the outcomes of patients who underwent autologous peripheral blood stem cell transplantation (auto-PBSCT; n=375) with those who underwent allogeneic bone marrow transplantation (allo-BMT; n=521) and allo-PBSCT (n=380) from MSDs for adults with AML/CR1, in which propensity score models were used to adjust selection biases among patients, primary physicians and institutions to overcome ambiguity in the patients' background information. Both the multivariate analysis and propensity score models indicated that the leukemia-free survival rate of auto PBSCT was not significantly different from that of allo-BMT (hazard ratio (HR), 1.23; 95% confidence interval (CI), 0.92 to 1.66; P=0.16) and allo-PBSCT (HR, 1.13; 95% CI, 0.85-1.51; P=0.40). The current results suggest that auto-PBSCT remains a promising alternative treatment for patients with AML/CR1 in the absence of an available MSD. PMID- 26808567 TI - Conjunctival polyploid cells and donor-derived myofibroblasts in ocular GvHD. AB - After allogeneic hematopoietic stem cell transplantation (allo-SCT), ocular GvHD is a common complication, typical symptoms being dry eye syndrome with features of fibrosis. In this study, we have identified and quantified two cell types myofibroblasts (MFB) and polyploid (PP) cells-in the conjunctival surface of allo SCT patients (pts) and have explored their kinetics and association with local and systemic GvHD. Results are compared with control groups of (a) pretransplant samples from allo-SCT patients, (b) recipients of autologous transplantation (auto-SCT) and (c) healthy controls. Imprint cytologies were obtained by pressing the conjunctival surface with a sterile, non-abrasive cellulose acetate filter (Millipore). After retraction, typically a monolayer of the outermost cells of the epithelium were retrieved. MFB were identified by immunofluorescent (IF) staining for alpha-smooth muscle protein. PP cells were detected by aberrant chromosome content analyzed via X/Y-FISH (X/Y fluorescence in situ hybridization). In female pts with a male donor (M?F group), donor genotype were identified by sex chromosome detection using FISH methodology. IF and FISH methods were applied in situ on the same filter, and amounts of MFB and PP cells are expressed as the percentage of all cells on the filter. In all, 70 samples from 46 pts were obtained 1-122 months after allo-SCT. The total MFB density (MFB(TOT)) was higher in allo-SCT pts compared with healthy individuals and auto SCT pts and increased by time after transplantation (P<0.001). In M?F recipients, this increase proved to be due to a significant (P<0.001) and gradual elevation of donor-derived MFB (MFB(XY)), whereas recipient-derived MFB (MFB(XX)) did not vary over time. Clinical ocular GvHD correlated with MFB(XY)/MFB(TOT) ratio (P=0.034), whereas no association between MFB(TOT) or MFB(XY) systemic GvHD was observed. In the M?F group (n=25), both MFB(XY) and MFB(XX) were detected on 28 of the 37 imprints (76%). In pts >36 months post transplant, on 11/12 imprints, a median of 9.4% (1.4-39%) MFB(XY) and 3.6% (0-11%) MFB(XX) was found. In one patient, 1.6% MFB(XY) were detected at 3 weeks post transplant. PP cells (6-24n), exclusively of recipient origin, were found to a median of 0.6% (0-37%). The PP cell density differed significantly (P<0.001) between time intervals, with a maximum 8.9% (0-35%) of all cells at 3-12 months. No correlation between PP cells and GvHD (ocular or systemic) was observed. The MFB has been indicated as a culprit in chronic inflammation and fibrosis. The observation that MFB(XY)/MFB(TOT) ratio correlated with ocular GvHD suggests a role of donor MFB in GvHD pathogenesis. The constant finding of recipient-derived MFB(XX) cells many years after transplant in pts with 100% donor hematopoiesis indicates that there is a non-hematopoietic differentiation route to MFB. The origin and role of PP cells after allo-SCT remains obscure. PMID- 26808568 TI - Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis. AB - There is currently a major concern regarding the optimal immunosuppression therapy to be administered after hematopoietic stem cell transplantation (HSCT) to reduce both the toxicity of GvHD and the rate of relapse. We report the outcome of high-risk leukemia children transplanted with a new way of managing cyclosporine (CsA)-based GvHD prophylaxis. A total of 110 HSCT in 109 ALL or AML children who received CsA without mycophenolate or methotrexate in matched related as well as in matched or mismatched unrelated stem cell transplantation were included. CsA dosage regimens were individualized to obtain specific trough blood concentrations values. The incidences of grade I-II and III-IV acute GvHD were 69.1% and 1.8%, respectively, and 8.4% for chronic GvHD. GvHD was neither more frequent nor severe in unrelated than in related HSCT. GvHD occurred in 87% of patients with a mean CsA trough concentration ?120 ng/mL versus 43% with concentration >120 ng/mL (P<0.0001). Five-year disease-free survival (DFS) and overall survival were 78% and 83.6%, respectively. DFS was 76.9% for ALL and 80.4% for AML patients. There was no difference in DFS between matched siblings and matched unrelated or mismatched unrelated HSCT. DFS in patients with minimal residual disease (MRD) ?10(-3) and in those with MRD <10(-3) before SCT was comparable. Our results indicate that a GvHD prophylaxis regimen based on CsA without mycophenolate or methotrexate is safe and effective whatever the donor compatibility is. These results suggest that GvL effect may be enhanced by this strategy of GvHD prophylaxis. PMID- 26808569 TI - Reduced intensity conditioning regimen with fludarabine, cyclophosphamide, low dose TBI and alemtuzumab leading to successful unrelated umbilical cord stem cell engraftment and survival in two children with dyskeratosis congenita. PMID- 26808570 TI - Successful matched sibling cord blood transplant for ALL in a child with constitutional mismatch repair deficiency syndrome. PMID- 26808571 TI - Astrovirus outbreak at a pediatric hematology and hematopoietic stem cell transplant unit despite strict hygiene rules. PMID- 26808572 TI - Is allogeneic transplant for solid tumors still alive? PMID- 26808573 TI - TCR-alpha/beta and CD19 depletion and treosulfan-based conditioning regimen in unrelated and haploidentical transplantation in children with acute myeloid leukemia. AB - We evaluated the depletion of TCR-alpha/beta cells from the graft of children with high-risk AML, who received transplantation from unrelated (n=20) and haploidentical donors (n=13). The preparative regimen included treosulfan, melphalan, fludarabine and anti-thymocyte globulin. Grafts were PBSC engineered by TCR-alpha/beta and CD19 depletion. The graft contained a median of 9 * 10(6)/kg of CD34+ and 20 * 10(3)/kg of alphabeta-T cells. Post-transplant immune suppression included tacrolimus till day +30 and Mtx in 21 patients, tacrolimus in 5, Mtx in 2 and no prophylaxis in 5 patients. Sixteen patients received native or TCR-alpha/beta-depleted donor lymphocytes at a median of 47 (40-204) days. Median follow-up is 1.76 years. Primary engraftment was achieved in 33 patients (100%). Cumulative incidence of acute GvHD (aGvHD) grade 2-3 was 39 (26-60)%, half of them had skin-only aGvHD. Cumulative incidence of chronic GvHD was 30(18 50)%. Transplant-related mortality is 10(4-26)%. Event-free survival (EFS) is 60(43-76)% and overall survival (OS) is 67(50-84)% at 2 years. In a subgroup of patients, who received transplantation in CR, EFS is 66(48-84)% and OS-72(53-90)% at 2 years. Our data suggest that TCR-alpha/beta and CD19 depletion is a robust method of graft manipulation, which can be used to engineer grafts for children with AML. PMID- 26808574 TI - IL-10 Accelerates Re-Endothelialization and Inhibits Post-Injury Intimal Hyperplasia following Carotid Artery Denudation. AB - The role of inflammation on atherosclerosis and restenosis is well established. Restenosis is thought to be a complex response to injury, which includes early thrombus formation, acute inflammation and neo-intimal growth. Inflammatory cells are likely contributors in the host response to vascular injury, via cytokines and chemokines secretion, including TNF-alpha (TNF). We have previously shown that IL-10 inhibits TNF and other inflammatory mediators produced in response to cardiovascular injuries. The specific effect of IL-10 on endothelial cell (ECs) biology is not well elucidated. Here we report that in a mouse model of carotid denudation, IL-10 knock-out mice (IL-10KO) displayed significantly delayed Re endothelialization and enhanced neo-intimal growth compared to their WT counterparts. Exogenous recombinant IL-10 treatment dramatically blunted the neo intimal thickening while significantly accelerating the recovery of the injured endothelium in WT mice. In vitro, IL-10 inhibited negative effects of TNF on ECs proliferation, ECs cell cycle, ECs-monocyte adhesion and ECs apoptosis. Furthermore, IL-10 treatment attenuated TNF-induced smooth muscle cells proliferation. Our data suggest that IL-10 differentially regulate endothelial and vascular smooth cells proliferation and function and thus inhibits neo intimal hyperplasia. Thus, these results may provide insights necessary to develop new therapeutic strategies to limit vascular restenosis during percutaneous coronary intervention (PCI) in the clinics. PMID- 26808575 TI - AK-1, a SIRT2 inhibitor, destabilizes HIF-1alpha and diminishes its transcriptional activity during hypoxia. AB - Sirtuin family proteins are involved in the regulation of hypoxic responses which are primarily dependent on a hypoxia-inducible factor (HIF). However, few studies have examined the use of sirtuin inhibitors to regulate HIF. The present study examined the effect of a SIRT2-specific inhibitor, AK-1, on hypoxic responses. Under hypoxic conditions, AK-1 increased the ubiquitination of HIF-1alpha in a VHL-dependent manner, leading to the degradation of HIF-1alpha via a proteasomal pathway. Downregulation of HIF-1alpha expression reduced its transcriptional activity and, eventually, reduced the expression of BNIP3, one of HIF-1 target genes, in AK-1-treated cells. These data demonstrate that SIRT2 inhibition attenuates hypoxic responses, and that SIRT2 inhibitors may have potential as treatments for hypoxia-associated pathological conditions. PMID- 26808576 TI - DNA methylation, histone acetylation and methylation of epigenetic modifications as a therapeutic approach for cancers. AB - Epigenetic modifications play important roles in regulating carcinogenesis, and specific epigenetic modifications have emerged as potential tumor markers. Herein, we summarize several types of epigenetic modifications, explore the role played by epigenetic modifications in gene regulation, and describe the patterns of epigenetic modifications in cancers. Since epigenetic modifications have been reported to regulate the Warburg effect in cancers, the roles of epigenetic modifications in sugar metabolism are discussed. In addition, oxidative stress may play an important role in carcinogenesis, and the role of oxidative stress and epigenetic modification in carcinogenesis is addressed. We also discuss the role of epigenetic modifications as therapeutic targets. Finally, the synergistic effects of the combined treatment of epigenetic regulator and anticancer drugs for cancer therapy are described. PMID- 26808577 TI - miR-206 functions as a novel cell cycle regulator and tumor suppressor in clear cell renal cell carcinoma. AB - PURPOSE: In this study we tried to systematically investigate the tumor suppressing microRNAs in ccRCC. MATERIALS AND METHODS: The MTS cell viability and colony formation assay were used to systematically detect the tumor suppressing ability of down-regulated miRNAs in ccRCC. Then miR-206 expression was detected by RT-qPCR and in situ hybridization in ccRCC cell lines and clinical samples. Oligonucleotides were used to overexpress or down-regulate miR-206. MTS cell viability, EdU cell proliferation, colony formation assay, flow cytometry, Xenograft subcutaneously and orthotopic implantations were done to examine tumor suppressing effects of miR-206 in vitro and in vivo. Luciferase assay was performed to verify the precise target of miR-206. RESULTS: We reviewed and experimentally analyzed the currently available miRNA expression profiles data of ccRCC and identified miR-206 as one of the most critical tumor-suppressing microRNAs in ccRCC. In addition, miR-206 inhibited ccRCC cell proliferation through inducing cell cycle arrest by directly targeting cell cycle related gene CDK4, CDK9 and CCND1. CONCLUSIONS: All these results suggested that miR-206 functioned as a novel cell cycle regulator and tumor suppressor in ccRCC and could be considered as a potential target for ccRCC therapy. PMID- 26808578 TI - A feed-forward regulatory loop between androgen receptor and PlncRNA-1 promotes prostate cancer progression. AB - We previously reported that PlncRNA-1, a long non-coding RNA that is up-regulated in prostate cancer (PCa), affects the proliferation and apoptosis of PCa cells. However, the molecular mechanisms underlying these effects remain largely unknown. In this study, we demonstrated that long non-coding RNA PlncRNA-1, whose expression is promoted by Androgen Receptor (AR), protects AR from microRNA mediated suppression in PCa cells. PlncRNA-1 knockdown resulted in the up regulation of a series of AR-targeting microRNAs, among which miR-34c and miR-297 were found to regulate both AR and PlncRNA-1 expression at the post transcriptional level. Functional analysis revealed that miR-34c and miR-297 overexpression down-regulated AR expression and inhibited the expression of downstream AR targets and that PlncRNA-1 overexpression rescued these effects. The association of PlncRNA-1 with tumor progression was also evaluated in mouse xenograft models, PCa tissues (16 paired samples), and blood samples (35 biopsy negative and 37 biopsy-positive). Together, the data generated in this study indicate that PlncRNA-1 sponges AR-targeting microRNAs to protect AR from microRNA-mediated down-regulation and that these events form a regulatory feed forward loop in the development of PCa. These findings suggest that PlncRNA-1 might potentially serve as a novel biomarker in PCa and that PlncRNA-1 might warrant further investigation to determine its potential role as a promising therapeutic target in PCa. PMID- 26808579 TI - SARI, a novel target gene of glucocorticoid receptor, plays an important role in dexamethasone-mediated killing of B lymphoma cells. AB - Dexamethasone (Dex) has been commonly used in lymphoma and leukemia treatment, but the detailed mechanisms are not fully understood. Suppressor of AP-1 regulated by interferon (SARI) has tumor-selective growth inhibitory effect. However, it's unclear whether SARI is involved in the Dex-mediated lymphoma growth suppression. In this study, we found that Dex-treated B lymphoma tissues had a higher level of SARI. Dex repressed the growth of B lymphoma cells and upregulated SARI expression by activating glucocorticoid receptor (GR) in vitro and in vivo. Silencing of SARI attenuated the Dex-mediated growth suppression of B lymphoma cells and inhibition of AP-1 activity. Reporter assays revealed that activation of GR enhanced the transcriptional activity of SARI promoter. EMSA and ChIP assays showed that GR directly bound to the ER9 element in SARI promoter region. These results for the first time demonstrated that SARI is a novel target gene of GR, and the upregulation of SARI plays an important role in Dex's killing effect on B lymphoma cells, suggesting that SARI may serve as a novel target and a potential indicator of Dex sensitivity in B lymphoma treatment. PMID- 26808580 TI - Psychoanalytic-Interactional Therapy versus Psychodynamic Therapy by Experts for Personality Disorders: A Randomized Controlled Efficacy-Effectiveness Study in Cluster B Personality Disorders. AB - BACKGROUND: With regard to cluster B personality disorders, most psychotherapeutic treatments focus on borderline personality disorder. Evidence based treatments for patients with other cluster B personality disorders are not yet available. Psychoanalytic-interactional therapy (PIT) represents a transdiagnostic treatment for severe personality disorders. PIT has been applied in clinical practice for many years and has proven effective in open studies. In a randomized controlled trial, we compared manual-guided PIT to nonmanualized pychodynamic therapy by experts in personality disorders (E-PDT) in patients with cluster B personality disorders. METHODS: In an inpatient setting, patients with cluster B personality disorders were randomly assigned to manual-guided PIT (n = 64) or nonmanualized E-PDT (n = 58). In addition, a quasi-experimental control condition was used (n = 46) including both patients receiving treatment as usual and patients waiting for treatment. Primary outcomes were level of personality organization and overall psychological distress. As secondary outcomes, depression, anxiety and interpersonal problems were examined. RESULTS: No significant improvements were found in the control patients. Both PIT and E-PDT achieved significant improvements in all outcome measures and were superior to the control condition. No differences were found between PIT and E-PDT in any outcome measure at the end of treatment. The type of cluster B personality disorder had no impact on the results. CONCLUSIONS: In an inpatient setting, both PIT and E-PDT proved to be superior to a control condition in cluster B personality disorders. In a head-to-head comparison, both treatments appeared to be equally effective. Further research on the treatment of cluster B personality disorders is required. PMID- 26808581 TI - Characterizing longitudinal changes in rabbit brains infected with Angiostrongylus Cantonensis based on diffusion anisotropy. AB - Angiostrongylus cantonensis has become a global source of infection in recent years, and the differential diagnosis and timely follow-up are crucial in the management of the infection. Magnetic resonance imaging (MRI) has been suggested as a non-invasive technique in characterizing and localizing lesions during the parasitic infections in the brain. Non-invasive diffusion tensor imaging (DTI) can be used to distinguish microscopic cerebral structures but cannot resolve the more complicated neural structure. Several methods have been proposed to overcome this limitation. One such method, generalized q-sampling imaging (GQI), can be applied to a variety of datasets, including the single shell, multi-shell or grid sampling schemes, which are believed to resolve complicated crossing fibers. This study aimed to characterize angiostrongyliasis in the rabbit brain over a 6-week period using anatomical and diffusion MRI, including DTI and GQI. Our anatomical T2WI and R2 mapping results showed that the ventricle size of the rabbit brain increased after A. cantonensis larvae infection, and the DTI and GQI indices both showed pathological changes in the corpus callosum, hippocampus and cortex over a 6-week infection period. These results were consistent with our histopathological findings. Our results demonstrated that the diagnosis of larvae infection using anatomical and diffusion MRI is possible and that follow-up characterization is informative in revealing the effects of angiostrongyliasis in various brain areas. These support the use of anatomical and diffusion MRI was helpful for diagnosis of eosinophilic meningitis caused by A. cantonensis infection. This non invasive MRI platform could be used to improve the management of eosinophilic meningitis or eosinophilic meningoencephalitis in humans. PMID- 26808582 TI - Data Sharing and the Journal. PMID- 26808583 TI - Relationship of Serum Adiponectin Levels and Metformin Therapy in Patients with Type 2 Diabetes. AB - We performed this meta-analysis to investigate and determine the role of metformin on serum adiponectin levels in Type 2 diabetes (T2DM) patients. Embase, Web of Science, Cochrane Library PubMed, and China National Knowledge Infrastructure (CNKI) were thoroughly searched. Eligible human studies assessing the association between serum adiponectin levels and metformin in patients were included, and data were extracted and then analyzed with STATA 12.0 statistical software. Eighteen cohort studies conducted among Asians and Caucasians from 2004 to 2013 were recruited. Post-treatment serum adiponectin level (mmol/l) was higher than pre-treatment levels in T2DM patients (SMD=0.19, 95% CI=0.09-0.30, p<0.001). Country-subgroup analysis showed that serum adiponectin levels in T2DM patients increased after the treatment of metformin in Italy (SMD=0.34, 95% CI=0.09-0.59, p=0.008). Further detection method and follow-up time subgroup analyses implied a positive association of metformin with serum adiponectin level in T2DM patients by using all ELISA, PETIA, and RIA in both<12 weeks and>=12 weeks subgroups (all p<0.05). The present meta-analysis provides compelling evidence that metformin may increase serum adiponectin levels when treating T2DM. Further studies should be promoted to explore the combined efficacy of metformin with other antidiabetic drugs, or developing new predictors with antidiabetic efficacy. PMID- 26808584 TI - MALDI imaging mass spectrometry as a novel tool for detecting histone modifications in clinical tissue samples. AB - Histone post-translational modifications (PTMs), histone variants and enzymes responsible for the incorporation or the removal of the PTMs are being increasingly associated with human disease. Combinations of histone PTMs and the specific incorporation of variants contribute to the establishment of cellular identity and hence are potential markers that could be exploited in disease diagnostics and prognostics and therapy response prediction. Due to the scarcity of suitable antibodies and the pre-requirement of tissue homogenization for more advanced analytical techniques, comprehensive information regarding the spatial distribution of these factors at the tissue level has been lacking. MALDI imaging mass spectrometry provides an ideal platform to measure histone PTMs and variants from tissues while maintaining the information about their spatial distribution. Discussed in this review are the relevance of histones in the context of human disease and the contribution of MALDI imaging mass spectrometry in measuring histones in situ. PMID- 26808585 TI - Predictors of cardiac morbidity in diabetic, new-onset diabetic and non-diabetic high-risk hypertensive patients: The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial. AB - Diabetic and new-onset diabetic patients with hypertension have higher cardiac morbidity than patients without diabetes. We aimed to investigate whether baseline predictors of cardiac morbidity, the major constituent of the primary endpoint in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, were different in patients with diabetes and new-onset diabetes compared to patients without diabetes. In total, 15,245 high-risk hypertensive patients in the VALUE trial were followed for an average of 4.2 years. At baseline, 5250 patients were diabetic by the 1999 World Health Organization criteria, 1298 patients developed new-onset diabetes and 8697 patients stayed non-diabetic during follow-up. Cardiac morbidity was defined as a composite of myocardial infarction and heart failure requiring hospitalization, and baseline predictors were identified by univariate and multivariate stepwise Cox regression analyses. History of coronary heart disease (CHD) and age were the most important predictors of cardiac morbidity in both diabetic and non-diabetic patients. History of CHD, history of stroke and age were the only significant predictors of cardiac morbidity in patients with new-onset diabetes. Predictors of cardiac morbidity, in particular history of CHD and age, were essentially the same in high-risk hypertensive patients with diabetes, new-onset diabetes and without diabetes who participated in the VALUE trial. PMID- 26808586 TI - Nanoclusters of CaSe in calcium-doped Bi2Se3 grown by molecular-beam epitaxy. AB - In calcium (Ca) doped Bi2Se3 films grown by molecular beam epitaxy, nanoclusters of CaSe are revealed by high-angle annular dark field imaging and energy dispersive x-ray spectroscopy analysis using a scanning transmission electron microscope. As the interface between the ordinary insulator CaSe and topological insulator, Bi2Se3, can host topological nontrivial interface state, this represents an interesting material system for further studies. We show by first principles total energy calculations that aggregation of Ca atoms in Bi2Se3 is driven by energy minimization and a preferential intercalation of Ca in the van der Waals gap between quintuple layers of Bi2Se3 induces reordering of atomic stacking and causes an increasing amount of stacking faults in film. The above findings also provide an explanation of less-than-expected electrical carrier (hole) concentrations in Ca-doped samples. PMID- 26808587 TI - Effect of Dietary Complex Lipids on the Biosynthesis of Piglet Brain Gangliosides. AB - Gangliosides, found in mammalian milk, are known for their roles in brain development of the newborn. However, the mechanism involved in the impact of dietary gangliosides on brain metabolism is not fully understood. The impact of diets containing complex lipids rich in milk-derived ganglioside GD3 on the biosynthesis of gangliosides (assessed from the incorporation of deuterium) in the frontal lobe of a piglet model is reported. Higher levels of incorporation of deuterium was observed in the GM1 and GD1a containing stearic acid in samples from piglets fed milk containing 18.2 MUg/mL of GD3 compared to that in those fed milk containing 25 MUg/mL of GD3. This could suggest that the gangliosides from the diet may be used as a precursor for de novo biosynthesis of brain gangliosides or lead to the reduction of de novo biosynthesis of these gangliosides. This effect was more pronounced in the left compared to that in the right brain hemisphere. PMID- 26808588 TI - Ultrasensitive In Situ Fluorescence Analysis using Modulated Fluorescence Interference Contrast at Nanostructured Polymer Surfaces. AB - The precise modulation of fluorescence interference contrast is achieved by introducing a nanoscopically engineered spacer layer prepared by chemical vapor deposition (CVD) of functional polymers. These novel imaging substrates are chemically identical throughout their entire detection area, yet present patterns of nanoscale thickness. A protein binding cascade is studied in real time and in the presence of high background noise. PMID- 26808589 TI - Plant subcellular proteomics: Application for exploring optimal cell function in soybean. AB - Plants have evolved complicated responses to developmental changes and stressful environmental conditions. Subcellular proteomics has the potential to elucidate localized cellular responses and investigate communications among subcellular compartments during plant development and in response to biotic and abiotic stresses. Soybean, which is a valuable legume crop rich in protein and vegetable oil, can grow in several climatic zones; however, the growth and yield of soybean are markedly decreased under stresses. To date, numerous proteomic studies have been performed in soybean to examine the specific protein profiles of cell wall, plasma membrane, nucleus, mitochondrion, chloroplast, and endoplasmic reticulum. In this review, methods for the purification and purity assessment of subcellular organelles from soybean are summarized. In addition, the findings from subcellular proteomic analyses of soybean during development and under stresses, particularly flooding stress, are presented and the proteins regulated among subcellular compartments are discussed. Continued advances in subcellular proteomics are expected to greatly contribute to the understanding of the responses and interactions that occur within and among subcellular compartments during development and under stressful environmental conditions. BIOLOGICAL SIGNIFICANCE: Subcellular proteomics has the potential to investigate the cellular events and interactions among subcellular compartments in response to development and stresses in plants. Soybean could grow in several climatic zones; however, the growth and yield of soybean are markedly decreased under stresses. Numerous proteomics of cell wall, plasma membrane, nucleus, mitochondrion, chloroplast, and endoplasmic reticulum was carried out to investigate the respecting proteins and their functions in soybean during development or under stresses. In this review, methods of subcellular-organelle enrichment and purity assessment are summarized. In addition, previous findings of subcellular proteomics are presented, and functional proteins regulated among different subcellular are discussed. Subcellular proteomics contributes greatly to uncovering responses and interactions among subcellular compartments during development and under stressful environmental conditions in soybean. PMID- 26808590 TI - Using a proteometabolomic approach to investigate the role of Dufour's gland in pheromone biosynthesis in the social wasp Polybia paulista. AB - : Dufour's gland is associated with the venom apparatuses of social wasps and bees. This location and its evolutionary adaptations indicate that it could be involved in the production of alarm pheromones in the social wasp Polybia paulista. To investigate this hypothesis, the volatile composition of this gland was analyzed and compared to that in the venom. Eighteen compounds were identified as secreted by Dufour's gland, and 16 of these compounds were also identified in the venom, suggesting that the compounds produced by the gland are secreted and mixed with venom in the venom reservoir of this wasp. These compounds were subjected to a field bioassay to investigate their potential action as alarm pheromones. Alcohols and aldehydes elicited the alert behavior in workers, luring them outside the nest, whereas acids attracted the workers in the direction of the source; fatty acid methyl esters elicited aggression. These results suggest that Dufour's gland produces alarm pheromones. To corroborate this hypothesis the proteomic complement of this gland was assigned using a shot gun strategy; 59 proteins were identified, and the results indicate specialization of Dufour's gland for the metabolism of fatty acids (elongation, esterification unsaturation, reduction, and decarboxylation) in the biosynthesis of alarm pheromones. BIOLOGICAL SIGNIFICANCE: The present knowledge about the role of Dufour's gland among aculeate Hymenoptera insects suggests that it may have many different roles related to the biosynthesis and secretion of chemical markers for different biological functions, though none are related to the elicitation of alarm behaviors for coordinating a mass attack of the colony against intruders. The present study combined the analysis of secreted volatile compounds (as metabolites) with proteome assignments and a field bioassay with synthetic compounds to clearly demonstrate that Dufour's gland does in fact biosynthesize alarm pheromones in social wasps. This strategy may be reproduced in other investigations related to pheromone production in other insects. PMID- 26808591 TI - Popliteal cysts in children: another look. AB - This retrospective review of 46 popliteal cysts seen in 44 patients at a pediatric orthopedic referral center clarifies the presenting symptomatology, associated conditions, and likely duration of a popliteal cyst, and the need for intervention. The patients were followed up for more than 1 year. Thirty-six of the 46 cysts with duration data showed no resolution of the popliteal cyst during the period of observation (average, 32.1 months). The 10 cysts that showed clinical resolution were present for an average of 16.9 months. The benign course of action for virtually all patients obviated the need for intervention and supports the adequacy of only clinical examination, with no need for recurrent sonography. PMID- 26808592 TI - Cell-based bioreporter assay coupled to HPLC micro-fractionation in the evaluation of antimicrobial properties of the basidiomycete fungus Pycnoporus cinnabarinus. AB - CONTEXT: Identification of bioactive components from complex natural product extracts can be a tedious process that aggravates the use of natural products in drug discovery campaigns. OBJECTIVE: This study presents a new approach for screening antimicrobial potential of natural product extracts by employing a bioreporter assay amenable to HPLC-based activity profiling. MATERIALS AND METHODS: A library of 116 crude extracts was prepared from fungal culture filtrates by liquid-liquid extraction with ethyl acetate, lyophilised, and screened against Escherichia coli using TLC bioautography. Active extracts were studied further with a broth microdilution assay, which was, however, too insensitive for identifying the active microfractions after HPLC separation. Therefore, an assay based on bioluminescent E. coli K-12 (pTetLux1) strain was coupled with HPLC micro-fractionation. RESULTS: Preliminary screening yielded six fungal extracts with potential antimicrobial activity. A crude extract from a culture filtrate of the wood-rotting fungus, Pycnoporus cinnabarinus (Jacq.) P. Karst. (Polyporaceae), was selected for evaluating the functionality of the bioreporter assay in HPLC-based activity profiling. In the bioreporter assay, the IC50 value for the crude extract was 0.10 mg/mL. By integrating the bioreporter assay with HPLC micro-fractionation, the antimicrobial activity was linked to LC UV peak of a compound in the chromatogram of the extract. This compound was isolated and identified as a fungal pigment phlebiarubrone. DISCUSSION AND CONCLUSION: HPLC-based activity profiling using the bioreporter-based approach is a valuable tool for identifying antimicrobial compound(s) from complex crude extracts, and offers improved sensitivity and speed compared with traditional antimicrobial assays, such as the turbidimetric measurement. PMID- 26808593 TI - Modular Optimization of a Hemicellulose-Utilizing Pathway in Corynebacterium glutamicum for Consolidated Bioprocessing of Hemicellulosic Biomass. AB - Hemicellulose, which is the second most abundant polysaccharide in nature after cellulose, has the potential to become a major feedstock for microbial fermentation to produce various biofuels and chemicals. To utilize hemicellulose economically, it is necessary to develop a consolidated bioprocess (CBP), in which all processes from biomass degradation to the production of target products occur in a single bioreactor. Here, we report a modularly engineered Corynebacterium glutamicum strain suitable for CBP using hemicellulosic biomass (xylan) as a feedstock. The hemicellulose-utilizing pathway was divided into three distinct modules, and each module was separately optimized. In the module for xylose utilization, the expression level of the xylose isomerase (xylA) and xylulokinase (xylB) genes was optimized with synthetic promoters of different strengths. Then, the module for xylose transport was engineered with combinatorial sets of synthetic promoters and heterologous transporters to achieve the fastest cell growth rate on xylose (0.372 h(-1)). Next, the module for the enzymatic degradation of xylan to xylose was also engineered with different combinations of promoters and signal peptides to efficiently secrete both endoxylanase and xylosidase into the extracellular medium. Finally, each optimized module was integrated into a single plasmid to construct a highly efficient xylan-utilizing pathway. Subsequently, the direct production of lysine from xylan was successfully demonstrated with the engineered pathway. To the best of our knowledge, this is the first report of the development of a consolidated bioprocessing C. glutamicum strain for hemicellulosic biomass. PMID- 26808594 TI - Sequential Inactivation of Gliotoxin by the S-Methyltransferase TmtA. AB - The epipolythiodioxopiperazine (ETP) gliotoxin mediates toxicity via its reactive thiol groups and thereby contributes to virulence of the human pathogenic fungus Aspergillus fumigatus. Self-intoxication of the mold is prevented either by reversible oxidation of reduced gliotoxin or by irreversible conversion to bis(methylthio)gliotoxin. The latter is produced by the S-methyltransferase TmtA and attenuates ETP biosynthesis. Here, we report the crystal structure of TmtA in complex with S-(5'-adenosyl)-l-homocysteine. TmtA features one substrate and one cofactor binding pocket per protein, and thus, bis-thiomethylation of gliotoxin occurs sequentially. Molecular docking of substrates and products into the active site of TmtA reveals that gliotoxin forms specific interactions with the protein surroundings, and free energy calculations indicate that methylation of the C10a SH group precedes alkylation of the C3-SH site. Altogether, TmtA is well suited to selectively convert gliotoxin and to control its biosynthesis, suggesting that homologous enzymes serve to regulate the production of their toxic natural sulfur compounds in a similar manner. PMID- 26808596 TI - Brief Report: Maternal Age of Menarche and Adiposity: Evidence from Hong Kong's "Children of 1997" Birth Cohort. AB - BACKGROUND: Earlier age of menarche predicts chronic diseases. Earlier maternal age of menarche is also associated with higher body mass index (BMI) and height into childhood. METHODS: We used generalized estimating equations in Hong Kong's "Children of 1997" birth cohort to examine the adjusted association of maternal age of menarche with BMI and height z score, and whether associations varied by maternal birthplace. RESULTS: Earlier maternal age of menarche was not associated with infant BMI but was associated subsequently with higher BMI in childhood and at puberty. Maternal age of menarche was negatively associated with height in children of Hong Kong-born mothers, but positively associated with infant length for children with mothers born in China (P value for interaction 0.02). CONCLUSION: These different patterns suggest drivers of adiposity and linear growth differ, and are more influential in some circumstances. Understanding these drivers may indicate setting-specific interventions to prevent childhood obesity. PMID- 26808595 TI - Childhood and Adolescent Pesticide Exposure and Breast Cancer Risk. AB - BACKGROUND: To date, epidemiologic studies have not strongly supported an association between pesticide exposure and breast cancer. However, few previous studies had the ability to assess specific time periods of exposure. Studies that relied on adult serum levels of metabolites of organochlorine pesticides may not accurately reflect exposure during developmental periods. Furthermore, exposure assessment often occurred after diagnosis and key tumor characteristics, such as hormone receptor status, have rarely been available to evaluate tumor subtype specific associations. We examined the association between pesticide exposure during childhood and adolescence and breast cancer risk in the prospective Sister Study cohort (N = 50,884 women) to assess this relation by tumor subtype. METHODS: During an average 5-year follow-up, 2,134 incident invasive and in situ breast cancer diagnoses were identified. Residential and farm exposure to pesticides were self-reported at study enrollment during standardized interviews. Multivariable hazard ratios and 95% confidence intervals for breast cancer risk were calculated with Cox proportional hazards regression. RESULTS: HRs were near null for the association between childhood/adolescent pesticide exposure and breast cancer risk overall or among ER+/PR+ invasive tumors. However, among women who were ages 0-18 before the ban of dichlordiphenyltrichloroethane in the US, exposure to fogger trucks or planes was associated with a hazard ratio = 1.3 for premenopausal breast cancer (95% confidence interval: 0.92, 1.7). CONCLUSION: These findings do not support an overall association between childhood and adolescent pesticide exposure and breast cancer risk. However, modest increases in breast cancer risk were associated with acute events in a subgroup of young women. PMID- 26808597 TI - Tumor Necrosis Factor-alpha Inhibitor Use and the Risk of Incident Hypertension in Patients with Rheumatoid Arthritis. AB - OBJECTIVE: To compare the risk of incident hypertension between initiators of tumor necrosis factor (TNF)-alpha inhibitors and initiators of nonbiologic disease modifying antirheumatic drugs (hereafter referred to as nonbiologics) in rheumatoid arthritis patients taking methotrexate monotherapy. METHODS: We conducted a cohort study using insurance claims data (2001-2012) from the US. We identified initiators of use of either TNF-alpha inhibitors or nonbiologics. Subsequent exposure to these agents was measured monthly in a time-varying manner. The outcome of interest was incident hypertension, defined by a diagnosis and a prescription for an antihypertensive drug. Marginal structural models estimated hazard ratios (HRs) adjusted for both baseline and time-varying confounders. To validate the primary analysis, we designed a verification analysis to evaluate a known association between leflunomide (a nonbiologic disease modifying agent) and hypertension. RESULTS: We identified 4,822 initiations of TNF-alpha inhibitor use and 2,400 of nonbiologic use. Crude incidence rates of hypertension per 1,000 person-years of follow-up were 36 (95% CI [confidence interval]: 32, 41) for the TNF-alpha inhibitor group and 42 (95% CI: 34, 51) for the nonbiologics group. The crude HR of TNF-alpha inhibitors versus nonbiologics for the risk of incident hypertension was 0.85 (95% CI: 0.67, 1.1). After adjusting for both baseline and time-varying covariates using marginal structural models, the HR was 0.95 (95% CI: 0.74, 1.2). In the verification analysis, the adjusted HR of incident hypertension was 2.3 (95% CI: 1.7, 3.0) in leflunomide initiators compared with methotrexate initiators. CONCLUSION: Treatment with TNF-alpha inhibitors was not associated with a reduced risk of incident hypertension compared with nonbiologics in rheumatoid arthritis patients.See Video Abstract at http://links.lww.com/EDE/B36. PMID- 26808598 TI - Anthropometry-based Obesity Phenotypes and Risk of Colorectal Adenocarcinoma: A Large Prospective Cohort Study in Norway. AB - BACKGROUND: It is unclear whether obesity phenotypes measured by different anthropometric indices are associated with a risk of colorectal adenocarcinoma by anatomical location. METHODS: We compiled harmonized population-based cohort studies (Cohort of Norway, CONOR) with 143,477 participants that were conducted between 1994 and 2010. General, abdominal, and gluteofemoral obesity were assessed by body mass index (BMI, kg/m(2)), waist circumference (cm), and hip circumference (cm). Other measures examined were waist to hip ratio, waist to height ratio, and body adiposity index. We performed Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of obesity relative to a risk of colorectal adenocarcinoma. RESULTS: In total, 2,044 incident cases of colorectal adenocarcinoma were identified. We observed a positive association between waist circumference (high versus low) and adenocarcinoma in the proximal colon (HR = 1.9, 95% CI = 1.5, 2.5) and distal colon (HR = 1.7, 95% CI = 1.3, 2.3) when adjusted for BMI. The association with waist circumference was especially strong in men. BMI was not associated with adenocarcinoma in the colon or rectum after adjusting for waist circumference. We found no association between hip circumference and colorectal adenocarcinoma. When adjusted for BMI plus waist circumference, body adiposity index was negatively associated with adenocarcinoma in the proximal or distal colon. CONCLUSION: Abdominal obesity, but not general or gluteofemoral obesity, was associated with an increased risk of adenocarcinoma in the proximal and the distal colon, especially in men. Muscularity may be negatively associated with risk of colon adenocarcinoma. PMID- 26808599 TI - Re: Mediators of the Effect of Body Mass Index on Coronary Heart Disease. PMID- 26808600 TI - Re: Lies, Damned Lies, and Health Inequality Measurements: Understanding the Value Judgments. PMID- 26808601 TI - Re: Is the Risk Difference Really a More Heterogeneous Measure? PMID- 26808602 TI - The Authors Respond. PMID- 26808603 TI - The Authors Respond. PMID- 26808604 TI - The Authors Respond. PMID- 26808605 TI - Modulating activity in the orbitofrontal cortex changes trustees' cooperation: A transcranial direct current stimulation study. AB - Trust is one of the most important factors in human society, as it pervades almost all domains of the society. The trusting behavior of trustors is dependent on the belief about the cooperative (reciprocal) level of trustees. Thence what are the motives underlying the cooperative behavior? An important explanation is that guilt aversion can motivate cooperative behavior. The right orbitofrontal cortex (OFC) is the guilt-specific region, while there is little understanding on the causal effect of this network. We explored the causal effect of the OFC on cooperative behavior using transcranial direct current stimulation (tDCS). Sixty participants played the trust game as trustees, and they received either anodal tDCS over the right OFC and simultaneously cathodal electrode over the right dorsolateral prefrontal cortex (DLPFC), or sham stimulation. Experimental results showed that participants as trustees transferred back more money in the tDCS treatment than sham stimulation. This suggests that the activity of the right OFC has causal effects on cooperative behavior. PMID- 26808606 TI - The neuroprotective effects of preconditioning exercise on brain damage and neurotrophic factors after focal brain ischemia in rats. AB - Preconditioning exercise can exert neuroprotective effects after stroke. However, the mechanism underlying these neuroprotective effects by preconditioning exercise remains unclear. We investigated the neuroprotective effects of preconditioning exercise on brain damage and the expression levels of the midkine (MK) and brain-derived neurotrophic factor (BDNF) after brain ischemia. Animals were assigned to one of 4 groups: exercise and ischemia (Ex), no exercise and ischemia (No-Ex), exercise and no ischemia (Ex-only), and no exercise and intact (Control). Rats ran on a treadmill for 30 min once a day at a speed of 25 m/min for 5 days a week for 3 weeks. After the exercise program, stroke was induced by a 60 min left middle cerebral artery occlusion using an intraluminal filament. The infarct volume, motor function, neurological deficits, and the cellular expressions levels of MK, BDNF, GFAP, PECAM-1, caspase 3, and nitrotyrosine (NT) were evaluated 48 h after the induction of ischemia. The infarct volume, neurological deficits and motor function in the Ex group were significantly improved compared to that of the No-Ex group. The expression levels of MK, BDNF, GFAP, and PECAM-1 were enhanced in the Ex group compared to the expression levels in the No-Ex group after brain ischemia, while the expression levels of activated caspase 3 and NT were reduced in the area surrounding the necrotic lesion. Our findings suggest that preconditioning exercise reduced the infract volume and ameliorated motor function, enhanced expression levels of MK and BDNF, increased astrocyte proliferation, increased angiogenesis, and reduced neuronal apoptosis and oxidative stress. PMID- 26808607 TI - Evaluation of the antidepressant- and anxiolytic-like activity of alpha spinasterol, a plant derivative with TRPV1 antagonistic effects, in mice. AB - The transient receptor potential vanilloid 1 (TRPV1) receptor has recently gained attention as a new molecular target in the treatment of mental disorders such as depression and anxiety. alpha-Spinasterol is a plant steroid that acts as a TRPV1 antagonist. The present study was undertaken to evaluate the antidepressant- and anxiolytic-like properties of alpha-spinasterol in mice. The obtained results showed that alpha-spinasterol (at doses of 1 and 2mg/kg) exerted anti-immobility effect in mice subjected to the forced swim test. Furthermore, co-administration of an ineffective dose of alpha-spinasterol (0.5mg/kg) with an ineffective dose of another TRPV1 antagonist - capsazepine (50 MUg/mouse) produced a synergistic effect in the forced swim test. This compound was, however, devoid of anxiolytic like effects in the elevated plus maze (at doses of 0.5-2mg/kg) and the light/dark box test (at a dose of 2mg/kg) in mice. Of note, alpha-spinasterol did not produce significant changes in body temperature and did not alter spontaneous locomotor activity in mice. The present study adds further support to the thesis that antagonism of the TRPV1 receptors may produce antidepressant effects. alpha Spinasterol may represent a new therapeutic approach towards the development of novel antidepressant therapy. However, further detailed studies on the antidepressant potential of alpha-spinasterol are warranted. PMID- 26808608 TI - Altered functional connectivity density in high myopia. AB - Abnormal visual experience can affect the brain structure and function. Visual functional performances of high myopia (HM) individuals were observed to be abnormal in contrast to emmetropics, even with a corrected visual acuity. Attention deficits and brain morphological changes have been revealed in the HM, but it is unknown whether there are functional connectivity (FC) alterations. The current study combined the resting-state functional connectivity density (FCD) mapping and seed-based correlation analysis to investigate FC alterations in the brain of HM. In our results, the HM exhibited decreased short- and long-range FCD in the posterior cingulate cortex/precuneus and decreased long-range FCD in the inferior temporal gyrus, supramarginal gyrus and rostrolateral prefrontal cortex. Specially, long-range FCD in the rostrolateral prefrontal cortex showed a significant positive correlation with the uncorrected visual acuity in the HM. Moreover, the HM showed significantly decreased FC not only between the supramarginal gyrus and rostrolateral prefrontal cortex, but also between networks they belong to, the ventral attention and frontoparietal control networks. These results provide evidence for the FC changes in the HM and may help to understand the attention deficits in myopes. PMID- 26808609 TI - Manual aspiration thrombectomy devices use in coronary interventions in 2016. AB - Percutaneous coronary intervention is a highly effective therapy of acute myocardial infarction. Restoration of microcirculation is however often sub optimal with negative impact on patient outcome. Distal thrombus embolization may contribute to this issue. Simple manual aspiration thrombectomy catheters were developed with aim of thrombus extraction. There are several of these devices with very similar design. Thrombotic or atheromatous tissue is successfully retrieved in over 70% of patients. The initial results of small, often single center studies have provided encouraging results. Unfortunately, three further studies clearly demonstrated lack of any clinical benefit and routine use of manual aspiration thrombectomy cannot be recommended. Small but statistically significant increase in stroke rate is the major safety issue. Selective use in patients with large thrombus burden or suboptimal flow or perfusion is likely to continue and needs to be scientifically studied. PMID- 26808610 TI - PKM2 released by neutrophils at wound site facilitates early wound healing by promoting angiogenesis. AB - Neutrophils infiltration/activation following wound induction marks the early inflammatory response in wound repair. However, the role of the infiltrated/activated neutrophils in tissue regeneration/proliferation during wound repair is not well understood. Here, we report that infiltrated/activated neutrophils at wound site release pyruvate kinase M2 (PKM2) by its secretive mechanisms during early stages of wound repair. The released extracellular PKM2 facilitates early wound healing by promoting angiogenesis at wound site. Our studies reveal a new and important molecular linker between the early inflammatory response and proliferation phase in tissue repair process. PMID- 26808611 TI - Analysis of alpha-glucosidase enzyme activity used in a rapid test for steam sterilization assurance. AB - AIMS: This study was to determine the sources, location and identity of alpha glucosidases in dormant/germinating/outgrowing spores and growing cells of Geobacillus stearothermophilus ATCC 7953, an enzymatic activity in spores used in rapid tests of steam sterilization. METHODS AND RESULTS: alpha-Glucosidase activity in spores and cells was determined measuring methylumbelliferyl-alpha-d glucoside (alpha-MUG) or alpha-MUG-6-phosphate hydrolysis fluorometrically. While alpha-MUG-6-phosphate was not hydrolysed by cell or spore extracts, assays with alpha-MUG showed that: (1) the alpha-glucosidase activity was inside and outside spores, and the activity outside spores was largely removed by buffer washes or heat activation, whereas alpha-glucosidase activity was only inside vegetative cells; (2) most alpha-glucosidase activity in cells and spores was soluble; (3) Western blots and enzyme inhibition using an anti-alpha-glucosidase antiserum identified >=2 alpha-glucosidases in spores and growing cells; (4) alpha glucosidase-specific activities were similar in dormant, germinated and outgrowing spore and growing cell extracts; and (5) significant alpha-glucosidase was synthesized during spore germination and outgrowth and cell growth, this synthesis was not repressed by glucose nor induced by alpha-MUG, but glucose inhibited alpha-MUG uptake. CONCLUSIONS: alpha-MUG hydrolysis by G. stearothermophilus is by alpha-MUG uptake and hydrolysis by >=2 alpha glucosidases associated with dormant spores and synthesized by germinating and outgrowing spores. The enzyme activity observed by sterilization assurance assays appears likely to come from heat-stable enzyme in the spore core and enzyme(s) synthesized in spore outgrowth. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this work provide new insight into the science behind a rapid test for steam sterilization assurance. PMID- 26808612 TI - The rapid immunosuppression in phytohemagglutinin-activated human T cells is inhibited by the proliferative Ca(2+) influx induced by progesterone and analogs. AB - Progesterone, an endogenous immunomodulator, suppresses human T-cell activation during pregnancy. A sustained Ca(2 +) influx is an important signal for T-cell proliferation after crosslinking of T-cell receptor/CD3 complexes by anti-CD3 antibodies or phytohemagglutinin (PHA). Progesterone targets cell membrane sites inducing rapid responses including elevated intracellular free calcium concentration ([Ca(2+)]i) and suppressed T-cell PHA-activated proliferation. Interestingly, both PHA and progesterone induce [Ca(2+)]i elevation, but it remains unclear whether the PHA-induced Ca(2+) influx is affected by progesterone leading to T-cell immunosuppression. Primary T-cells were isolated from human peripheral blood and the quench effect on intracellular fura-2 fluorescence of Mn(2+) was used to explore the responses to Ca(2+) influx with cell proliferation being determined by MTT assay. PHA-stimulated Ca(2+) influx was dose-dependently suppressed by progesterone and its agonist R5020, which correlated with PHA activated T-cell proliferation inhibition. A similar dose-dependent suppression effect on cellular Ca(2+) influx and proliferation occurred with the TRPC channel inhibitor BTP2 and selective TRPC3 channel inhibitor Pyr3. In addition, two progesterone analogs, Org OD 02-0 and 20alpha-hydroxyprogesterone (20alpha-OHP), also produced dose-dependent suppression of Ca(2+) influx, but had no effect on proliferation. Finally, inhibition of PHA-activated T-cell proliferation by progesterone is further suppressed by 20alpha-OHP, but not by Org OD 02-0. Overall, progesterone and R5020 are able to rapidly decrease PHA-stimulated sustained Ca(2+) influx, probably via blockade of TRPC3 channels, which suppresses T-cell proliferation. Taken together, the roles of progesterone and its analogs regarding the rapid response Ca(2+) influx need to be further explored in relation to cytokine secretion and proliferation in activated T cells. PMID- 26808613 TI - Health services use and costs in people with intellectual disability: building a context knowledge base for evidence-informed policy. AB - PURPOSE OF REVIEW: We summarize the research published between 2011 and 2015 in healthcare utilization and costs for persons with intellectual disabilities/intellectual developmental disorders with a particular focus on context studies for evidence-informed policy. RECENT FINDINGS: Persons with intellectual disability show higher unmet needs and lower use of promotion and prevention services and generic health services. Use of generic psychiatric services varies across countries. Persons with intellectual disability and comorbid mental disorders have the highest rates of specialized service use, costs, and unmet needs. International and national cost-of-illness studies show the high impact of intellectual disability in the total direct health costs of mental disorders at least in Europe. On the contrary, the burden-of-illness studies show conflicting results in intellectual disability. SUMMARY: Contextual studies of healthcare and costs have improved the knowledge base for evidence informed planning in intellectual disability in a number of countries. However, only two of these studies have used local atlases of healthcare for improving decision making. The paucity of information on prevalence, comorbidity, and demographic indicators hampers the advance of evidence-informed policy in intellectual disability. PMID- 26808614 TI - Correlation of climbing perception and eye movements during daytime and nighttime takeoffs using a flight simulator. AB - CONCLUSION: This study suggests that the subjective climbing perception can be quantitatively evaluated using values calculated from induced eye movements, and the findings may aid in the detection of pilots who are susceptible to spatial disorientation in a screening test. OBJECTIVE: The climbing perception experienced by a pilot during takeoff at night is stronger than that experienced during the day. To investigate this illusion, this study assessed eye movements and analyzed their correlation with subjective climbing perception during daytime and nighttime takeoffs. METHODS: Eight male volunteers participated in this study. A simulated aircraft takeoff environment was created using a flight simulator and the maximum slow-phase velocities and vestibulo-ocular reflex gain of vertical eye movements were calculated during takeoff simulation. RESULTS: Four of the eight participants reported that their perception of climbing at night was stronger, while the other four reported that there was no difference between day and night. These perceptions were correlated with eye movements; participants with a small difference in the maximum slow-phase velocities of their downward eye movements between daytime and nighttime takeoffs indicated that their perception of climbing was the same under the two conditions. PMID- 26808617 TI - Caregiver Leave-Taking in Spain: Rate, Motivations, and Barriers. AB - This paper aims to (1) determine the rate of (full- and part-time) caregiver leave-taking in Spain, (2) identify the reasons conducive to a more intense use of this resource, and (3) ascertain the main obstacles to its use, as perceived by caregivers. All 896 people covered by the sample were engaging in paid work and had cared for dependent adults in the last 12 years. This resource, in particular the full-time alternative, was found to be a minority option. The data showed that legal, work-related, and family and gender norm issues are the four types of factors that determine the decision to take such leaves. The most significant obstacles to their use are the forfeiture of income and the risk of losing one's job. Our results suggest that income replacement during a leave would increase the take-up of these resources. Moreover, enlargement of public care services would promote the use of leave as a free choice of caregivers. PMID- 26808615 TI - Association between Functional Small Airway Disease and FEV1 Decline in Chronic Obstructive Pulmonary Disease. AB - RATIONALE: The small conducting airways are the major site of airflow obstruction in chronic obstructive pulmonary disease and may precede emphysema development. OBJECTIVES: We hypothesized a novel computed tomography (CT) biomarker of small airway disease predicts FEV1 decline. METHODS: We analyzed 1,508 current and former smokers from COPDGene with linear regression to assess predictors of change in FEV1 (ml/yr) over 5 years. Separate models for subjects without and with airflow obstruction were generated using baseline clinical and physiologic predictors in addition to two novel CT metrics created by parametric response mapping (PRM), a technique pairing inspiratory and expiratory CT images to define emphysema (PRM(emph)) and functional small airways disease (PRM(fSAD)), a measure of nonemphysematous air trapping. MEASUREMENTS AND MAIN RESULTS: Mean (SD) rate of FEV1 decline in ml/yr for GOLD (Global Initiative for Chronic Obstructive Lung Disease) 0-4 was as follows: 41.8 (47.7), 53.8 (57.1), 45.6 (61.1), 31.6 (43.6), and 5.1 (35.8), respectively (trend test for grades 1-4; P < 0.001). In multivariable linear regression, for participants without airflow obstruction, PRM(fSAD) but not PRM(emph) was associated with FEV1 decline (P < 0.001). In GOLD 1-4 participants, both PRM(fSAD) and PRM(emph) were associated with FEV1 decline (P < 0.001 and P = 0.001, respectively). Based on the model, the proportional contribution of the two CT metrics to FEV1 decline, relative to each other, was 87% versus 13% and 68% versus 32% for PRM(fSAD) and PRM(emph) in GOLD 1/2 and 3/4, respectively. CONCLUSIONS: CT-assessed functional small airway disease and emphysema are associated with FEV1 decline, but the association with functional small airway disease has greatest importance in mild-to-moderate stage chronic obstructive pulmonary disease where the rate of FEV1 decline is the greatest. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764). PMID- 26808616 TI - The Inflammasome and the Epidermal Growth Factor Receptor (EGFR) Are Involved in the Staphylococcus aureus-Mediated Induction of IL-1alpha and IL-1beta in Human Keratinocytes. AB - Staphylococcus (S.) aureus is an important pathogen causing various infections including those of the skin. Keratinocytes are able to sense invading S. aureus and to initiate a fast defense reaction by the rapid release of innate defense mediators such as antimicrobial peptides and cytokines. There is increasing evidence that the cytokines IL-1alpha and IL-1beta, which both signal through the IL-1 receptor, play an important role in cutaneous defense against S. aureus. The aim of this study was to gain more insight into the underlying mechanisms leading to the S. aureus-induced IL-1alpha and IL-1beta expression in keratinocytes. Infection of human primary keratinocytes with S. aureus led to the induction of gene expression and protein secretion of IL-1alpha and IL-1beta. Full S. aureus induced IL-1 protein release required the inflammasome components caspase-1 and ASC (apoptosis-associated speck-like protein containing a CARD) whereas gene induction of IL-1alpha and IL-beta by S. aureus was not dependent on caspase-1 and ASC. Since patients receiving anti-cancer therapy by inhibition of the epidermal growth factor receptor (EGFR) often suffer from skin infections caused by S. aureus we additionally evaluated whether the EGFR pathway may be involved in the IL-1alpha and IL-1beta induction by S. aureus. Inactivation of the EGFR with a blocking antibody decreased the S. aureus-mediated IL-1alpha and IL-1beta induction in primary keratinocytes. Moreover, the use of siRNA experiments revealed that ADAM17 (A Disintegrin and A Metalloprotease 17), a metalloproteinase known to mediate the shedding and release of EGFR ligands, was required for full induction of IL-1alpha and IL-1beta in keratinocytes infected with S. aureus. A failure of keratinocytes to adequately upregulate IL-1alpha and IL-1beta may promote S. aureus skin infections. PMID- 26808618 TI - Immigration and Sleep Problems in a Southern European Country: Do Immigrants Get the Best Sleep? AB - This study analyzes the differences in the prevalence of insomnia symptoms and nonrestorative sleep (NRS) between people born in Spain and immigrants from 7 countries with most immigrants in Spain. Data come from the 2006 Spanish National Health Survey. The sample was composed of all individuals aged 16 to 64 years from Spain and the 7 countries with most immigrants in Spain (N = 22,224). In both sexes, people from Bolivia had a higher prevalence of insomnia symptoms and NRS. Conversely, people from Ecuador, Morocco, and Romania had less insomnia symptoms and NRS than Spanish-born participants. No differences were found between Spanish-born participants and Colombian, Peruvian, and Argentinian women. Poor living conditions in the country of origin and in the host country, discrimination, and culturally related lifestyles could be related to poorer sleep health among Bolivian men. Acculturation may explain the similar sleep health patterns noted between Spanish-born participants and long-term immigrants. PMID- 26808619 TI - Cognitive Event-Related Potentials in Patients With Adenoid Hypertrophy: A Case Control Pilot Study. AB - PURPOSE: Children with adenoid hypertrophy commonly have sleep-disordered breathing. Sleep-disordered breathing is associated with various neurocognitive problems. The aim of this study was to assess the cognitive function in those patients using cognitive event-related potentials. METHODS: Twenty-three patients with moderate to severe adenoid hypertrophy were compared with 20 healthy controls. The intelligence quotient was performed for all study participants. The latencies of the N200, P300 peaks and the amplitudes of the N200/P300 components of event-related potentials were recorded. The above variables were measured at baseline for both patients and control groups and 2 months after adenoidectomy for the patient group. RESULTS: There was no significant difference between patients and controls regarding full intelligence quotient scales. P300 latency was significantly prolonged in patient group compared with the healthy controls. Moreover, postoperative P300 latency was significantly reduced compared with the preoperative P300 latency. Postoperative P300 latency was not statistically different from healthy controls' data. CONCLUSIONS: P300 latency delay may reflect some sort of cognitive impairment in patients with adenoid hypertrophy. This delay was reversible after adenoidectomy. Event-related potentials may help for assessment of cognitive functions in patients with adenoid hypertrophy. PMID- 26808620 TI - Proposal for a Standard Format for Neurophysiology Data Recording and Exchange. AB - The lack of interoperability between information networks is a significant source of cost in health care. Standardized data formats decrease health care cost, improve quality of care, and facilitate biomedical research. There is no common standard digital format for storing clinical neurophysiologic data. This review proposes a new standard file format for neurophysiology data (the bulk of which is video-electroencephalographic data), entitled the Multiscale Electrophysiology Format, version 3 (MEF3), which is designed to address many of the shortcomings of existing formats. MEF3 provides functionality that addresses many of the limitations of current formats. The proposed improvements include (1) hierarchical file structure with improved organization; (2) greater extensibility for big data applications requiring a large number of channels, signal types, and parallel processing; (3) efficient and flexible lossy or lossless data compression; (4) industry standard multilayered data encryption and time obfuscation that permits sharing of human data without the need for deidentification procedures; (5) resistance to file corruption; (6) facilitation of online and offline review and analysis; and (7) provision of full open source documentation. At this time, there is no other neurophysiology format that supports all of these features. MEF3 is currently gaining industry and academic community support. The authors propose the use of the MEF3 as a standard format for neurophysiology recording and data exchange. Collaboration between industry, professional organizations, research communities, and independent standards organizations is needed to move the project forward. PMID- 26808621 TI - Higher Tinzaparin Dosing Is Needed to Achieve Target Anti-Xa Levels in Pediatric Cardiac Intensive Care Patients. AB - OBJECTIVES: This study was conducted to evaluate tinzaparin dosing and therapeutic drug monitoring. DESIGN: Retrospective study. SETTING: Single tertiary-level PICU. PATIENTS: Tinzaparin doses and anti-Xa levels from all children admitted to a PICU (from October 1, 2010, to December 31, 2013) were retrospectively analyzed. Thirty-nine children, median age of 13 months (interquartile range, 73 mo), with 46 episodes of newly started therapeutic tinzaparin were identified. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Local hospital policy is to determine the first anti-Xa level after 3-4 doses, 4 hours post dose, targeting 0.5-1.0 IU/mL for therapeutic dosing. First anti-Xa levels were determined after 3.8 (+/- 2.4; range, 1-14) doses and were below the target range in 37 of 46 episodes (76%) of tinzaparin use: mean, 0.30 (+/- 0.11) IU/mL. Tinzaparin was then increased by 23% (+/- 19) in 23 of 37 episodes (62%), and further anti-Xa levels were determined. In 14 episodes, further levels were not available because of cessation of tinzaparin therapy. Target anti-Xa levels, 0.69 (+/- 0.24) IU/mL, were eventually reached in the PICU in 22 patients after a mean of 8.8 (+/- 7.3) doses. In the entire cohort, the dose required to achieve target anti-Xa levels was significantly higher (+51 [+/- 62] U/kg; p = 0.003) than the recommended starting dose. CONCLUSIONS: Target anti-Xa levels were reached with tinzaparin dosing in PICU patients after more than 8 doses, warranting further dose-effect research. Especially in the younger age group, substantially higher dose requirements than proposed in the internationally used guidelines are required. With the results of our study, we suggest a different therapeutic drug monitoring approach than that currently used. PMID- 26808622 TI - Outcomes of Single-Ventricle Patients Supported With Extracorporeal Membrane Oxygenation. AB - OBJECTIVES: Extracorporeal membrane oxygenation is often used in children with single-ventricle anomalies. We aimed to describe extracorporeal membrane oxygenation use in single-ventricle patients to test the hypothesis that despite increasing prevalence, mortality has not improved and overall burden measure by hospital charges and length of stay have increased. DESIGN: Retrospective analysis of the Healthcare Cost and Utilization Project Kids' Inpatient Database was performed with sample weighting to generate national estimates. PATIENTS: Pediatric patients (age <= 20) with a diagnosis of single ventricle heart disease requiring extracorporeal membrane oxygenation support from 2000 to 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Seven hundred one children (95% CI, 559-943) with single ventricle were supported with extracorporeal membrane oxygenation in the reporting period. Mortality was 57% and did not improve over time (2000 = 52%, 2003 = 63%, 2006 = 57%, and 2009 = 55%; p = 0.66). Single-ventricle patients who required extracorporeal membrane oxygenation were more likely to have had a cardiac procedure (90% vs 46%; p < 0.001), a diagnosis of arrhythmia (22% vs 13%; p < 0.001), cerebrovascular or neurologic insult (9% vs 1%; p < 0.001), heart failure (24% vs 12%; p < 0.001), acute renal failure (28% vs 3%; p < 0.001), or sepsis (28% vs 8%; p < 0.001). By multivariable analysis, acute renal failure was a risk factor for mortality (adjusted odds ratio, 3.12; 95% CI, 1.95-4.98; p < 0.001). The length of stay for single ventricle patients with extracorporeal membrane oxygenation increased from 25.2 days in 2000 to 55.6 days in 2009 (p < 0.001). Total inflation-adjusted charges increased from $358,021 (95% CI, $278,658-439,765) in 2000 to $732,349 (95% CI, $671,781-792,917) in 2009 (p < 0.001). CONCLUSIONS: Extracorporeal membrane oxygenation support is uncommon with single-ventricle admissions occurring in 2.3% of all hospitalizations. Among those patients, the mortality rate was 57% with no change over time. Acute renal failure was an independent risk factor for mortality during hospitalization. In addition, length of stay for these patients increased and hospital charges doubled. Further studies are needed to determine suitability and cost-effectiveness of extracorporeal membrane oxygenation in single-ventricle patients. PMID- 26808623 TI - A Novel Combined-Catheter to Monitor Left and Right Atrial Pressures: A Simple and Reliable Method for Pediatric Cardiac Surgery. AB - OBJECTIVE: To introduce a novel combined-catheter to monitor left and right atrial pressures. DESIGN: Prospective observational study. SETTING: Fuwai Hospital, China. PATIENTS: A total of 113 pediatric patients (77 men), median age 10.3 months, admitted between July 10, 2014, and February 5, 2015, were divided into two groups: the novel-catheter group and the traditional-method group. INTERVENTIONS: All patients received routine anesthesia and surgery. Left atrial pressure and central venous pressure (an estimate of right atrial pressure), measured through a catheter needle during surgery, were identified as the "gold standard." A novel combined-catheter, composed of a reformed triple-lumen catheter with a microtube inserted within its central cavity, was used in the novel-catheter group. A traditional triple-lumen catheter to monitor central venous pressure plus another single-lumen catheter to monitor left atrial pressure were used in the traditional-method group. MEASUREMENTS AND MAIN RESULTS: The novel combined-catheter could accurately monitor left atrial pressure and central venous pressure. Pressure values measured by the novel catheter correlated well with the gold standard (left atrial pressure, R = 0.98; central venous pressure, R = 0.99). Bland-Altman analyses revealed good agreement between pressures measured by the novel catheter and the gold standard. The absolute value of maximum difference was 0.67 mm Hg for left atrial pressure and 0.33 mm Hg for central venous pressure, which are acceptable in clinical practice. Left atrial pressure-monitoring catheter displaced into the right atrium occurred significantly less frequently in the novel-catheter group when compared with the traditional-method group (5 and 12 cases, respectively). CONCLUSIONS: This novel combined-catheter was safe and reliable at monitoring left and right atrial pressures, and infusion involved only one catheter without the disadvantages of the traditional method. This new novel method may be particularly useful in pediatric open-heart surgery. PMID- 26808624 TI - Predictors of Repeat Exchange Transfusion for Severe Neonatal Hyperbilirubinemia. AB - OBJECTIVES: To identify the predictors of repeat exchange transfusion among infants with severe hyperbilirubinemia. DESIGN: Retrospective cross-sectional study. SETTING: A referral children's hospital in inner-city Lagos, Nigeria. PATIENTS: Infants who received exchange transfusion for severe hyperbilirubinemia from January 2012 to December 2014. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The predictors of repeat exchange transfusion were identified among all infants who had at least one exchange transfusion using multivariable logistic regression. A total of 352 infants with mean peak total serum bilirubin of 26.32 +/- 7.96 mg/dL received exchange transfusion; of these, 49 (13.9%) with mean peak total serum bilirubin of 32.85 +/- 10.54 mg/dL had repeat exchange transfusion. More than two thirds of infants who received exchange transfusion and repeat exchange transfusion were male, and at least one third had ABO incompatibility. No infant had more than two exchange transfusions. The mean age of admission was approximately 5 days (range, 1-14 d). Peak total serum bilirubin greater than or equal to 30 mg/dL (odds ratio, 2.88; 95% CI, 1.46-5.70) and acute bilirubin encephalopathy (odds ratio, 2.37; 95% CI, 1.18-4.77) were predictive of repeat exchange transfusion. CONCLUSIONS: Acute bilirubin encephalopathy and excessive total serum bilirubin levels at least 30 mg/dL are predictive of repeat exchange transfusion. A risk assessment framework that combines total serum bilirubin levels, acute bilirubin encephalopathy status, and risk factors of neurotoxicity should be considered for the timely detection and monitoring of infants at risk of repeat exchange transfusion. PMID- 26808625 TI - Tudor-SN Interacts with Piwi Antagonistically in Regulating Spermatogenesis but Synergistically in Silencing Transposons in Drosophila. AB - Piwi proteins associate with piRNAs and functions in epigenetic programming, post transcriptional regulation, transposon silencing, and germline development. However, it is not known whether the diverse functions of these proteins are molecularly separable. Here we report that Piwi interacts with Tudor-SN (Tudor staphylococcal nuclease, TSN) antagonistically in regulating spermatogenesis but synergistically in silencing transposons. However, it is not required for piRNA biogenesis. TSN is known to participate in diverse molecular functions such as RNAi, degradation of hyper-edited miRNAs, and spliceosome assembly. We show that TSN colocalizes with Piwi in primordial germ cells (PGCs) and embryonic somatic cells. In adult ovaries and testes, TSN is ubiquitously expressed and enriched in the cytoplasm of both germline and somatic cells. The tsn mutants display a higher mitotic index of spermatogonia, accumulation of spermatocytes, defects in meiotic cytokinesis, a decreased number of spermatids, and eventually reduced male fertility. Germline-specific TSN-expression analysis demonstrates that this function is germline-dependent. Different from other known Piwi interters, TSN represses Piwi expression at both protein and mRNA levels. Furthermore, reducing piwi expression in the germline rescues tsn mutant phenotype in a dosage dependent manner, demonstrating that Piwi and TSN interact antagonistically in germ cells to regulate spermatogenesis. However, the tsn deficiency has little, if any, impact on piRNA biogenesis but displays a synergistic effect with piwi mutants in transposon de-silencing. Our results reveal the biological function of TSN and its contrasting modes of interaction with Piwi in spermatogenesis, transposon silencing, and piRNA biogenesis. PMID- 26808626 TI - Association of DNA Methylation at CPT1A Locus with Metabolic Syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. AB - In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 x 10(-7) was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = 2.6x10(-14) and P for cg17058475 = 1.2x10(-9)). Significant associations were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our findings suggest that methylation in CPT1A is a promising epigenetic marker for MetS risk which could become useful as a treatment target in the future. PMID- 26808627 TI - Assessment of Markers of Antimalarial Drug Resistance in Plasmodium falciparum Isolates from Pregnant Women in Lagos, Nigeria. AB - BACKGROUND: The use of antimalarial drugs for prevention and treatment is a major strategy in the prevention of malaria in pregnancy. Although sulphadoxine pyrimethamine (SP) is currently recommended for intermittent preventive treatment of malaria during pregnancy in Nigeria, previously used drugs for prophylaxis such as chloroquine (CQ) and pyrimethamine are accessible as they are purchased over the counter. This study describes the markers of absence or presence of resistance to quinoline (Pfcrt and Pfmdr 1) and type 1 antifolate antimalarial medicines (Pfdhfr). METHODS: Plasmodium falciparum-positive dried blood spots from pregnant women attending antenatal clinics for the first time during current pregnancy were investigated for the presence of mutations at codons 72-76 of Plasmodium falciparum chloroquine resistance transporter (Pfcrt) gene by real time polymerase chain reaction (PCR) using haplotype-specific probes. PCR followed by sequence analysis was used to identify mutations at codons 86, 184, 1034, 1042 and 1246 of P. falciparum multi-drug resistance-1 (Pfmdr1) gene; and codons 16, 50, 51, 59, 108, 140 and 164 of Pfdhfr gene. RESULTS: Two haplotypes of Pfcrt (n = 54) were observed: CVMNK 13(24.2%) and CVIET 41 (75.9%) of the samples. The SVMNT haplotype was absent in this population. The Pfmdr1 (n = 28) haplotypes were NYSND 15(53.6%), YYSND 5(17.9%), NFSND 6(21.4%) and YFSND 2(7.1%). The Pfdhfr (n = 15) were ACNCSVI 4(26.7%), and ACICNSVI 1(6.7%) and ACIRNVI 10 (66.7%). The rate of occurrence of Pfcrt 76T, Pfdhfr108N, Pfmdr186Y and 184F were 75.9%, 73.3%, 25% and 28.1% respectively. The Pfmdr1 86Y was associated with low parasitaemia (median = 71 parasites/MUl, P = 0.024) while Pfcrt 76T was associated with young maternal age (mean 24.1 +/- 4.5 years; P = 0.006). The median parasitaemia were similar (P>0.05) in wild and mutant strains of Pfcrt 76, Pfmdr1 184 and Pfdhfr 108. There was no association between gravidity or gestational age of the women and presence of mutations in the Pfcrt, Pfmdr1 or Pfdhfr genes (P>0.05). CONCLUSION: Markers of resistance to chloroquine and pyrimethamine were high, whereas cycloguanil-resistance marker was not present in the studied population. The low level of mutations in the Pfmdr1gene indicates likely efficacy of amodiaquine against malaria in pregnancy. PMID- 26808628 TI - Type I and Type II Interferon Coordinately Regulate Suppressive Dendritic Cell Fate and Function during Viral Persistence. AB - Persistent viral infections are simultaneously associated with chronic inflammation and highly potent immunosuppressive programs mediated by IL-10 and PDL1 that attenuate antiviral T cell responses. Inhibiting these suppressive signals enhances T cell function to control persistent infection; yet, the underlying signals and mechanisms that program immunosuppressive cell fates and functions are not well understood. Herein, we use lymphocytic choriomeningitis virus infection (LCMV) to demonstrate that the induction and functional programming of immunosuppressive dendritic cells (DCs) during viral persistence are separable mechanisms programmed by factors primarily considered pro inflammatory. IFNgamma first induces the de novo development of naive monocytes into DCs with immunosuppressive potential. Type I interferon (IFN-I) then directly targets these newly generated DCs to program their potent T cell immunosuppressive functions while simultaneously inhibiting conventional DCs with T cell stimulating capacity. These mechanisms of monocyte conversion are constant throughout persistent infection, establishing a system to continuously interpret and shape the immunologic environment. MyD88 signaling was required for the differentiation of suppressive DCs, whereas inhibition of stimulatory DCs was dependent on MAVS signaling, demonstrating a bifurcation in the pathogen recognition pathways that promote distinct elements of IFN-I mediated immunosuppression. Further, a similar suppressive DC origin and differentiation was also observed in Mycobacterium tuberculosis infection, HIV infection and cancer. Ultimately, targeting the underlying mechanisms that induce immunosuppression could simultaneously prevent multiple suppressive signals to further restore T cell function and control persistent infections. PMID- 26808630 TI - Propofol-induced Inhibition of Catecholamine Release Is Reversed by Maintaining Calcium Influx. AB - BACKGROUND: Propofol (2,6-diisopropylphenol) is one of the most frequently used anesthetic agents. One of the main side effects of propofol is to reduce blood pressure, which is thought to occur by inhibiting the release of catecholamines from sympathetic neurons. Here, the authors hypothesized that propofol-induced hypotension is not simply the result of suppression of the release mechanisms for catecholamines. METHODS: The authors simultaneously compared the effects of propofol on the release of norepinephrine triggered by high K-induced depolarization, as well as ionomycin, by using neuroendocrine PC12 cells and synaptosomes. Ionomycin, a Ca ionophore, directly induces Ca influx, thus bypassing the effect of ion channel modulation by propofol. RESULTS: Propofol decreased depolarization (high K)-triggered norepinephrine release, whereas it increased ionomycin-triggered release from both PC12 cells and synaptosomes. The propofol (30 MUM)-induced increase in norepinephrine release triggered by ionomycin was dependent on both the presence and the concentration of extracellular Ca (0.3 to 10 mM; n = 6). The enhancement of norepinephrine release by propofol was observed in all tested concentrations of ionomycin (0.1 to 5 MUM; n = 6). CONCLUSIONS: Propofol at clinically relevant concentrations promotes the catecholamine release as long as Ca influx is supported. This unexpected finding will allow for a better understanding in preventing propofol-induced hypotension. PMID- 26808631 TI - Anesthesia-induced Suppression of Human Dorsal Anterior Insula Responsivity at Loss of Volitional Behavioral Response. AB - BACKGROUND: It has been postulated that a small cortical region could be responsible for the loss of behavioral responsiveness (LOBR) during general anesthesia. The authors hypothesize that any brain region demonstrating reduced activation to multisensory external stimuli around LOBR represents a key cortical gate underlying this transition. Furthermore, the authors hypothesize that this localized suppression is associated with breakdown in frontoparietal communication. METHODS: During both simultaneous electroencephalography and functional magnetic resonance imaging (FMRI) and electroencephalography data acquisition, 15 healthy volunteers experienced an ultraslow induction with propofol anesthesia while a paradigm of multisensory stimulation (i.e., auditory tones, words, and noxious pain stimuli) was presented. The authors performed separate analyses to identify changes in (1) stimulus-evoked activity, (2) functional connectivity, and (3) frontoparietal synchrony associated with LOBR. RESULTS: By using an FMRI conjunction analysis, the authors demonstrated that stimulus-evoked activity was suppressed in the right dorsal anterior insula cortex (dAIC) to all sensory modalities around LOBR. Furthermore, the authors found that the dAIC had reduced functional connectivity with the frontoparietal regions, specifically the dorsolateral prefrontal cortex and inferior parietal lobule, after LOBR. Finally, reductions in the electroencephalography power synchrony between electrodes located in these frontoparietal regions were observed in the same subjects after LOBR. CONCLUSIONS: The authors conclude that the dAIC is a potential cortical gate responsible for LOBR. Suppression of dAIC activity around LOBR was associated with disruption in the frontoparietal networks that was measurable using both electroencephalography synchrony and FMRI connectivity analyses. PMID- 26808632 TI - Classically Activated Macrophages Protect against Lipopolysaccharide-induced Acute Lung Injury by Expressing Amphiregulin in Mice. AB - BACKGROUND: Alveolar macrophages (AMs) activated into M1 phenotype are involved in the development of lipopolysaccharide-induced acute lung injury (ALI). However, whether AMs express amphiregulin and what roles amphiregulin plays in lipopolysaccharide-induced ALI remain poorly understood. METHODS: Acute lung injury was induced by intratracheal instillation of lipopolysaccharide in male C57BL/6 mice. Lung injury scores, level of protein, and level of neutrophils in bronchial alveolar lavage fluid of lipopolysaccharide-induced ALI mice were compared with those in mice challenged with recombinant exogenous amphiregulin and antiamphiregulin antibody. Amphiregulin expression in macrophages and neutrophils in bronchial alveolar lavage fluid of lipopolysaccharide-induced ALI mice was determined by using immunofluorescence technique and further detected in M0, M1, and M2 phenotypes of both peritoneal macrophages and AMs. The effect of amphiregulin on apoptosis of MLE12 cells and activation of epithelial growth factor receptor-AKT pathway were, respectively, examined by using flow cytometry and western blotting. RESULTS: Alveolar macrophages were found to highly express amphiregulin in ALI mice. Amphiregulin neutralization aggravated, whereas recombinant exogenous amphiregulin attenuated lipopolysaccharide-induced ALI in mice (n = 6). In cultured AMs and peritoneal macrophages, amphiregulin was mainly generated by M1, rather than M0 or M2 phenotype (n = 5). Apoptosis ratio of lipopolysaccharide-challenged MLE12 cells was significantly reduced by recombinant exogenous amphiregulin from 16.60 +/- 1.82 to 9.47 +/- 1.67% (n = 5) but significantly increased from 17.45 +/- 1.13 to 21.67 +/- 1.10% (n = 5) after stimulation with supernatant of M1-polarized AM media conditioned with amphiregulin-neutrolizing antibody. Western blotting revealed that amphiregulin activated epithelial growth factor receptor and AKT in the lung tissues and MLE12 cells (n = 5). CONCLUSIONS: Different from the common notion that classically activated AMs have just a detrimental effect on the lung tissues, the results of this study showed that classically activated AMs also exerted a protective effect on the lung tissues by producing high-level amphiregulin in lipopolysaccharide induced ALI. PMID- 26808629 TI - Cerebral Oximetry Monitoring to Maintain Normal Cerebral Oxygen Saturation during High-risk Cardiac Surgery: A Randomized Controlled Feasibility Trial. AB - BACKGROUND: Cerebral oxygen desaturation during cardiac surgery has been associated with adverse perioperative outcomes. Before a large multicenter randomized controlled trial (RCT) on the impact of preventing desaturations on perioperative outcomes, the authors undertook a randomized prospective, parallel arm, multicenter feasibility RCT to determine whether an intervention algorithm could prevent desaturations. METHODS: Eight Canadian sites randomized 201 patients between April 2012 and October 2013. The primary outcome was the success rate of reversing cerebral desaturations below 10% relative to baseline in the intervention group. Anesthesiologists were blinded to the cerebral saturation values in the control group. Intensive care unit personnel were blinded to cerebral saturation values for both groups. Secondary outcomes included the area under the curve of cerebral desaturation load, enrolment rates, and a 30-day follow-up for adverse events. RESULTS: Cerebral desaturations occurred in 71 (70%) of the 102 intervention group patients and 56 (57%) of the 99 control group patients (P = 0.04). Reversal was successful in 69 (97%) of the intervention group patients. The mean cerebral desaturation load (SD) in the operating room was smaller for intervention group patients compared with control group patients (104 [217] %.min vs. 398 [869] %.min, mean difference, -294; 95% CI, -562 to -26; P = 0.03). This was also true in the intensive care unit (P = 0.02). There were no differences in adverse events between the groups. CONCLUSIONS: Study sites were successful in reversal of desaturation, patient recruitment, randomization, and follow-up in cardiac surgery, supporting the feasibility of conducting a large multicenter RCT. PMID- 26808633 TI - Resolvin D1 Inhibits Mechanical Hypersensitivity in Sciatica by Modulating the Expression of Nuclear Factor-kappaB, Phospho-extracellular Signal-regulated Kinase, and Pro- and Antiinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion. AB - BACKGROUND: Accumulating evidence indicates that spinal inflammatory and immune responses play an important role in the process of radicular pain caused by intervertebral disk herniation. Resolvin D1 (RvD1) has been shown to have potent antiinflammatory and antinociceptive effects. The current study was undertaken to investigate the analgesic effect of RvD1 and its underlying mechanism in rat models of noncompressive lumbar disk herniation. METHODS: Rat models of noncompressive lumber disk herniation were established, and mechanical thresholds were evaluated using the von Frey test during an observation period of 21 days (n = 8/group). Intrathecal injection of vehicle or RvD1 (10 or 100 ng) was performed for three successive postoperative days. On day 7, the ipsilateral spinal dorsal horns and L5 dorsal root ganglions (DRGs) were removed to assess the expressions of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-10, and transforming growth factor-beta1 (TGF-beta1) and the activation of nuclear factor-kappaB (NF-kappaB)/p65 and phospho-extracellular signal-regulated kinase (p-ERK) signaling (n = 30/group). RESULTS: The application of nucleus pulposus to L5 DRG induced prolonged mechanical allodynia, inhibited the production of IL-10 and TGF-beta1, and up-regulated the expression of TNF-alpha, IL-1beta, NF kappaB/p65, and p-ERK in the spinal dorsal horns and DRGs. Intrathecal injection of RvD1 showed a potent analgesic effect, inhibited the up-regulation of TNF alpha and IL-1beta, increased the release of IL-10 and TGF-beta1, and attenuated the expression of NF-kappaB/p65 and p-ERK in a dose-dependent manner. CONCLUSIONS: The current study showed that RvD1 might alleviate neuropathic pain via regulating inflammatory mediators and NF-kappaB/p65 and p-ERK pathways. Its antiinflammatory and proresolution properties may offer novel therapeutic approaches for the management of neuropathic pain. PMID- 26808634 TI - Perioperative Opioids and Public Health. PMID- 26808635 TI - Anesthetizing the Self: The Neurobiology of Humbug. PMID- 26808636 TI - Mitochondrial DNA: An Endogenous Trigger for Immune Paralysis. AB - BACKGROUND: Critically ill patients are at high risk to suffer from sepsis, even in the absence of an initial infectious source, but the molecular mechanisms for their increased sepsis susceptibility, including a suppressed immune system, remain unclear. Although microbes and pathogen-associated molecular pattern are accepted inducers of sepsis and septic immunosuppression, the role of endogenous Toll-like receptor (TLR) ligands, such as mitochondrial DNA (mtDNA), in altering the immune response is unknown. METHODS: Mitochondrial DNA serum concentrations of the mitochondrial genes D-Loop and adenosine triphosphatase 6 were determined (quantitative polymerase chain reaction) in 165 septic patients and 50 healthy volunteers. Furthermore, cytotoxic T-cell activity was analyzed in wild-type and TLR9 knockout mice, with/without previous mtDNA administration, followed by injection of an ovalbumin-expressing adenoviral vector. RESULTS: Mitochondrial DNA serum concentrations were increased in septic patients (adenosine triphosphatase 6, 123-fold; D-Loop, 76-fold, P < 0.0001) compared with volunteers. Furthermore, a single mtDNA injection caused profound, TLR9-dependent immunosuppression of adaptive T-cell cytotoxicity in wild-type but not in TLR9 knockout mice and evoked various immunosuppressive mechanisms including the destruction of the splenic microstructure, deletion of cross-presenting dendritic cells, and up-regulation of programmed cell death ligand 1 and indoleamine 2,3 dioxygenase. Several of these findings in mice were mirrored in septic patients, and mtDNA concentrations were associated with an increased 30-day mortality. CONCLUSIONS: The findings of this study imply that mtDNA, an endogenous danger associated molecular pattern, is a hitherto unknown inducer of septic immunoparalysis and one possible link between initial inflammation and subsequent immunosuppression in critically ill patients. PMID- 26808637 TI - Differential Suppression of Spontaneous and Noxious-evoked Somatosensory Cortical Activity by Isoflurane in the Neonatal Rat. AB - BACKGROUND: The effect of neonatal anesthesia and pain on the developing brain is of considerable clinical importance, but few studies have evaluated noxious surgical input to the infant brain under anesthesia. Herein, the authors tested the effect of increasing isoflurane concentration on spontaneous and evoked nociceptive activity in the somatosensory cortex of rats at different postnatal ages. METHODS: Intracortical extracellular field potentials evoked by hind paw C fiber electrical stimulation were recorded in the rat somatosensory cortex at postnatal day (P) 7, P14, P21, and P30 during isoflurane anesthesia (n = 7 per group). The amplitudes of evoked potentials and the energies of evoked oscillations (1 to 100 Hz over 3 s) were measured after equilibration at 1.5% isoflurane and during step increases in inspired isoflurane. Responses during and after plantar hind paw incision were compared at P7 and P30 (n = 6 per group). RESULTS: At P7, cortical activity was silent at 1.5% isoflurane but noxious evoked potentials decreased only gradually in amplitude and energy with step increases in isoflurane. The resistance of noxious-evoked potentials to isoflurane at P7 was significantly enhanced after surgical hind paw incision (69 +/- 16% vs. 6 +/- 1% in nonincised animals at maximum inspired isoflurane). This resistance was age dependent; at P14 to P30, noxious-evoked responses decreased sharply with increasing isoflurane (step 3 [4%] P7: 50 +/- 9%, P30: 4 +/- 1% of baseline). Hind paw incision at P30 sensitized noxious-evoked potentials, but this was suppressed by higher isoflurane concentrations. CONCLUSIONS: Despite suppression of spontaneous activity, cortical-evoked potentials are more resistant to isoflurane in young rats and are further sensitized by surgical injury. PMID- 26808638 TI - More Than Anyone Else: Preemies Need Good Analgesia. PMID- 26808639 TI - Synthesis, Biological Activity, and NMR-Based Structural Studies of Deltorphin I Analogs Modified in Message Domain with a New alpha,alpha-Disubstituted Glycines. AB - This article describes new deltorphin I analogs in which phenylalanine residues were replaced by the corresponding (R) or (S)-alpha-benzyl-beta-azidoalanine, alpha-benzyl-beta-(1-pyrrolidinyl)alanine, alpha-benzyl-beta-(1 piperidinyl)alanine, and alpha-benzyl-beta-(4-morpholinyl)-alanine residues. The potency and selectivity of the new analogs were evaluated by a competitive receptor binding assay in the rat brain using [(3) H]DAMGO (a MU ligand) and [(3) H]DELT (a delta ligand). The affinity of analogs containing (R) or (S)-alpha benzyl-beta-azidoalanine in position 3 to delta-receptors strongly depended on the chirality of the alpha,alpha-disubstituted residue. The conformational behavior of peptides modified with (R) or (S)-alpha-benzyl-beta-(1 piperidinyl)Ala, which displays the opposite selectivity, was analyzed by (1) H and (13) C NMR. The MU-selective Tyr-d-Ala-(R)-alpha-benzyl-beta-(1 piperidinyl)Ala-Asp-Val-Val-Gly-NH2 lacks the helical conformation observed in the delta-selective Tyr-d-Ala-(S)-alpha-benzyl-beta-(1-piperidinyl)Ala-Asp-Val Val-Gly-NH2 . Our results support the proposal that differences between delta- and MU-selective opioid peptides are attributable to the presence or absence of a spatial overlap between the N-terminal message domain and the C-terminal address domain. PMID- 26808640 TI - The effects of an intraperitoneal single low dose of ketamine in attenuating the postoperative skin/muscle incision and retraction-induced pain related to the inhibition of N-methyl-D-aspartate receptors in the spinal cord. AB - BACKGROUND: Chronic postoperative pain (CPOP) is a common clinical problem which might be related to central sensitization. It has been widely accepted that NMDA (N-methyl-D-aspartate) receptors are among the triggers of central sensitization. Ketamine is a non-competitive NMDA receptor antagonist that is widely used in alleviating postoperative pain, but its effect on CPOP has been rarely reported. In the present study, the skin/muscle incision and retraction (SMIR) model was used to investigate the role of NMDARs in chronic postoperative pain and the effect of an intraperitoneal single low dose ketamine (10mg/kg) of attenuating SMIR-induced CPOP. METHODS: We assessed pain behaviours after a SMIR operation by paw withdrawal threshold (PWMT) and paw withdrawal latency (PWMTL). Western blotting were performed to examine the role of NMDARs in SMIR-induced CPOP and the effect of ketamine on the expression and phosphorylation of NMDARs. RESULTS: The SMIR operation induced long-lasting mechanical hyperalgesia, and the up regulation of phosphorylated NMDARs and total NMDARs at the spinal level. A single intraperitoneal administration of low dose ketamine (10mg/kg) during surgery alleviated pain behaviors and inhibited the up-regulation of phosphorylated NMDARs and total NMDARs. CONCLUSIONS: Our datas suggested that NMDARs play important roles in SMIR-induced CPOP. A single intraperitoneal low dose of ketamine could attenuate SMIR-induced CPOP, which might be associated with the inhibition of NMDARs. Our finding might provide a new, simple method of addressing CPOP. PMID- 26808641 TI - Dopamine receptor D2 and catechol-O-methyltransferase gene polymorphisms associated with anorexia nervosa in Chinese Han population: DRD2 and COMT gene polymorphisms were associated with AN. AB - Dopamine receptor D2 (DRD2) and catechol-O-methyltransferase (COMT) are important in dopamine system which is proved to be associated with food-anticipatory behavior, food restriction, reward and motivation. This has made them good candidates for anorexia nervosa (AN). The aim of this work is to explore the roles of DRD2 (rs1800497) and COMT (rs4680, rs4633, rs4818) gene polymorphisms in the susceptibility of AN within the Chinese Han population. We recruited 260AN patients with DSM-IV diagnosis criteria, and 247 unrelated, normal weight controls. DRD2 (rs1800497) and COMT (rs4680, rs4633, rs4818) were genotyped in all subjects. We found rs1800497 and rs4633 were associated with the susceptibility of AN within the Chinese Han sample, and allele C of rs1800497 was a protective factor. There was a gene-gene interaction between rs1800497 of DRD2 gene and rs4633 of COMT gene. We concluded that rs1800497 and rs4633 play important roles in the AN susceptibility with respect to the Chinese Han population. The gene-gene interaction between DRD2 and COMT contributes to the risk of AN. PMID- 26808642 TI - A sensitive and practical RP-HPLC-FLD for determination of the low neuroactive amino acid levels in body fluids and its application in depression. AB - Ion-exchange high performance liquid chromatography (HPLC) generally fails as a method to determine low levels of free amino acids (AAs) in body fluids. Here we present a modified reversed-phase HPLC (RP-HPLC) protocol for the determination of AAs in body fluids and its application in mood disorder patients. We improved a previous research protocol by modifying i) sample preparation, including deproteination, ii) derivitization, including derivating agent and condition, and iii) sample separation, which is mainly determined by the pH value, the components and the additives of the mobile phases. The combination of these modifications, together with fluorescence detection (FLD), allows sensitive and practical determination of free AA levels in body fluids of depressive patients. This protocol was validated by determining the postmortem cerebrospinal fluid (CSF) glutamic acid (Glu) and gamma-aminobutyric acid (GABA) levels of 8 major depressive disorder (MDD) patients, 9 bipolar disorder (BD) patients, and 19 well matched controls, while also testing the plasma and CSF AA levels of living MDD patients. CSF Glu and GABA levels were both significantly decreased in MDD but not in BD patients. The data indicate that this RP-HPLC-FLD protocol is applicable for detection of low levels of neuroactive AAs in body fluids, as well as for routine clinical applications. PMID- 26808643 TI - Platelet-activating factor attenuation of long-term potentiation in rat hippocampal slices via protein tyrosine kinase signaling. AB - It is well established that HIV-1-infected mononuclear phagocytes release platelet activating factor (PAF) and elevated levels of PAF have been detected in blood and in the cerebrospinal fluid (CSF) of acquired immunodeficiency syndrome (AIDS) patients with HIV-associated neurocognitive disorders (HAND). It is our hypothesis that the elevated levels of PAF alter long-term potentiation (LTP) in the hippocampus, leading to neurocognitive dysfunction. To test this hypothesis, we studied the effects of PAF on LTP in the CA1 region of rat hippocampal slices. Our results showed incubation of hippocampal slices with PAF attenuated LTP. The PAF-mediated attenuation was blocked by ginkgolide B, a PAF receptor antagonist, suggesting PAF attenuation of LTP via PAF receptors. Application of lyso-PAF, an inactive PAF analog, had no apparent effect on LTP. Further investigation revealed an involvement of tyrosine kinase in PAF attenuation of LTP, which was demonstrated by lavendustin A (a specific protein tyrosine kinase inhibitor) blockage of PAF attenuation of LTP. As LTP is widely considered as the cellular and synaptic basis for learning and memory, the attenuation of LTP by PAF may contribute at least in part to the HAND pathogenesis. PMID- 26808644 TI - Functional Characterization of Pseudomonas Contact Dependent Growth Inhibition (CDI) Systems. AB - Contact-dependent inhibition (CDI) toxins, delivered into the cytoplasm of target bacterial cells, confer to host strain a significant competitive advantage. Upon cell contact, the toxic C-terminal region of surface-exposed CdiA protein (CdiA CT) inhibits the growth of CDI- bacteria. CDI+ cells express a specific immunity protein, CdiI, which protects from autoinhibition by blocking the activity of cognate CdiA-CT. CdiA-CT are separated from the rest of the protein by conserved peptide motifs falling into two distinct classes, the "E. coli"- and "Burkholderia-type". CDI systems have been described in numerous species except in Pseudomonadaceae. In this study, we identified functional toxin/immunity genes linked to CDI systems in the Pseudomonas genus, which extend beyond the conventional CDI classes by the variability of the peptide motif that delimits the polymorphic CdiA-CT domain. Using P. aeruginosa PAO1 as a model, we identified the translational repressor RsmA as a negative regulator of CDI systems. Our data further suggest that under conditions of expression, P. aeruginosa CDI systems are implicated in adhesion and biofilm formation and provide an advantage in competition assays. All together our data imply that CDI systems could play an important role in niche adaptation of Pseudomonadaceae. PMID- 26808646 TI - Hazelnut and neuroprotection: Improved memory and hindered anxiety in response to intra-hippocampal Abeta injection. AB - OBJECTIVES: Corylus avellana L. (hazelnut) is known to be a delicious and nutritious food. This study was carried out to evaluate the use of hazelnut as a therapy for memory impairment because in Iranian traditional medicine, it is recommended for those suffering from a particular type of dementia, with symptoms of Alzheimer's disease. METHODS: In this study, rats were fed with hazelnut kernel [(without skin) 800 mg/kg/day] during 1 week before stereotaxic surgery to 24 hours before behavioral testing (in general, for 16 consecutive days) and the effect of hazelnut eating on memory, anxiety, neuroinflammation and apoptosis was assessed in the amyloid beta-injected rat. RESULTS: The results of this study showed that feeding with hazelnut improved memory, (which was examined by using Y maze test and shuttle box apparatus), and reduced anxiety-related behavior, that was evaluated using elevated plus maze. Also, western blotting analysis of cyclooxygenase-2, interleukin-1beta, tumor necrosis factor-alpha, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, and caspase-3 showed that hazelnut has an ameliorating effect on the neuroinflammation and apoptosis caused by Abeta. DISCUSSION: These findings suggest that hazelnut, as a dietary supplement, improves healthy aging and could be a beneficial diet for the treatment of AD. PMID- 26808647 TI - Quantitative profiling of prostaglandins as oxidative stress biomarkers in vitro and in vivo by negative ion online solid phase extraction - Liquid chromatography tandem mass spectrometry. AB - Free radical-mediated oxidation of arachidonic acid to prostanoids has been implicated in a variety of pathophysiological conditions such as oxidative stress. Here, we report on the development of a liquid chromatography-mass spectrometry method to measure several classes of prostaglandin derivatives based on regioisomer-specific mass transitions down to levels of 20 pg/ml applied to the measurement of prostaglandin biomarkers in primary hepatocytes. The quantitative profiling of prostaglandin derivatives in rat and human hepatocytes revealed the increase of several isomers on stress response. In addition to the well-established markers for oxidative stress such as 8-iso-prostaglandin F2alpha and the prostaglandin isomers PE2 and PD2, this method revealed a significant increase of 15R-prostaglandin D2 from 236.1 +/- 138.0 pg/1E6 cells in untreated rat hepatocytes to 2001 +/- 577.1 pg/1E6 cells on treatment with ferric NTA (an Fe(3+) chelate with nitrilotriacetic acid causing oxidative stress in vitro as well as in vivo). Like 15R-prostaglandin D2, an unassigned isomer that revealed a more significant increase than commonly analyzed prostaglandin derivatives was identified. Mass spectrometric detection on a high-resolution instrument enabled high-quality quantitative analysis of analytes in plasma levels from rat experiments, where increased concentrations up to 23-fold change treatment with Fe(III)NTA were observed. PMID- 26808648 TI - Beyond efficacy: The full public health impact of vaccines. AB - There is an active discussion in the public health community on how to assess and incorporate, in addition to safety and measures of protective efficacy, the full public health value of preventive vaccines into the evidence-based decision making process of vaccine licensure and recommendations for public health use. The conference "Beyond efficacy: the full public health impact of vaccines in addition to efficacy measures in trials" held in Annecy, France (June 22-24, 2015) has addressed this issue and provided recommendations on how to better capture the whole public health impact of vaccines. Using key examples, the expert group stressed that we are in the midst of a new paradigm in vaccine evaluation, where all aspects of public health value of vaccines beyond efficacy should be evaluated. To yield a wider scope of vaccine benefits, additional measures such as vaccine preventable disease incidence, overall efficacy and other outcomes such as under-five mortality or non-etiologically confirmed clinical syndromes should be assessed in addition to traditional efficacy or effectiveness measurements. Dynamic modelling and the use of probe studies should also be considered to provide additional insight to the full public health value of a vaccine. The use of burden reduction and conditional licensure of vaccines based on collection of outcome results should be considered by regulatory agencies. PMID- 26808649 TI - Inhibition of hIAPP Amyloid Aggregation and Pancreatic beta-Cell Toxicity by OH Terminated PAMAM Dendrimer. AB - Human islet amyloid polypeptide (hIAPP, or amylin) forms amyloid deposits in the islets of Langerhans, a phenomenon that is associated with type-2 diabetes impacting millions of people worldwide. Accordingly, strategies against hIAPP aggregation are essential for the prevention and eventual treatment of the disease. Here, it is shown that generation-3 OH-terminated poly(amidoamine) dendrimer, a polymeric nanoparticle, can effectively halt the aggregation of hIAPP and shut down hIAPP toxicity in pancreatic MIN6 and NIT-1 cells as well as in mouse islets. This finding is supported by high-throughput dynamic light scattering experiment and thioflavin T assay, where the rapid evolution of hIAPP nucleation and elongation processes is halted by the addition of the dendrimer up to 8 h. Discrete molecular dynamics simulations further reveal that hIAPP residues bound strongly with the dendrimer near the c-terminal portion of the peptide, where the amyloidogenic sequence (residues 22-29) locates. Furthermore, simulations of hIAPP dimerization reveal that binding with the dendrimer significantly reduces formation of interpeptide contacts and hydrogen bonds, thereby prohibiting peptide self-association and amyloidosis. This study points to a promising nanomedicinal strategy for combating type-2 diabetes and may have broader implications for targeting neurological disorders whose distinct hallmark is also amyloid fibrillation. PMID- 26808651 TI - Treating breathlessness in lung cancer patients: the potential of breathing training. PMID- 26808650 TI - Lysine and Leucine Deficiencies Affect Myocytes Development and IGF Signaling in Gilthead Sea Bream (Sparus aurata). AB - Optimizing aquaculture production requires better knowledge of growth regulation and improvement in diet formulation. A great effort has been made to replace fish meal for plant protein sources in aquafeeds, making necessary the supplementation of such diets with crystalline amino acids (AA) to cover the nutritional requirements of each species. Lysine and Leucine are limiting essential AA in fish, and it has been demonstrated that supplementation with them improves growth in different species. However, the specific effects of AA deficiencies in myogenesis are completely unknown and have only been studied at the level of hepatic metabolism. It is well-known that the TOR pathway integrates the nutritional and hormonal signals to regulate protein synthesis and cell proliferation, to finally control muscle growth, a process also coordinated by the expression of myogenic regulatory factors (MRFs). This study aimed to provide new information on the impact of Lysine and Leucine deficiencies in gilthead sea bream cultured myocytes examining their development and the response of insulin like growth factors (IGFs), MRFs, as well as key molecules involved in muscle growth regulation like TOR. Leucine deficiency did not cause significant differences in most of the molecules analyzed, whereas Lysine deficiency appeared crucial in IGFs regulation, decreasing significantly IGF-I, IGF-II and IGF-IRb mRNA levels. This treatment also down-regulated the gene expression of different MRFs, including Myf5, Myogenin and MyoD2. These changes were also corroborated by a significant decrease in proliferation and differentiation markers in the Lysine deficient treatment. Moreover, both Lysine and Leucine limitation induced a significant down-regulation in FOXO3 gene expression, which deserves further investigation. We believe that these results will be relevant for the production of a species as appreciated for human consumption as it is gilthead sea bream and demonstrates the importance of an adequate level of Lysine in fishmeal diet formulation for optimum growth. PMID- 26808652 TI - Two Horizontally Transferred Xenobiotic Resistance Gene Clusters Associated with Detoxification of Benzoxazolinones by Fusarium Species. AB - Microbes encounter a broad spectrum of antimicrobial compounds in their environments and often possess metabolic strategies to detoxify such xenobiotics. We have previously shown that Fusarium verticillioides, a fungal pathogen of maize known for its production of fumonisin mycotoxins, possesses two unlinked loci, FDB1 and FDB2, necessary for detoxification of antimicrobial compounds produced by maize, including the gamma-lactam 2-benzoxazolinone (BOA). In support of these earlier studies, microarray analysis of F. verticillioides exposed to BOA identified the induction of multiple genes at FDB1 and FDB2, indicating the loci consist of gene clusters. One of the FDB1 cluster genes encoded a protein having domain homology to the metallo-beta-lactamase (MBL) superfamily. Deletion of this gene (MBL1) rendered F. verticillioides incapable of metabolizing BOA and thus unable to grow on BOA-amended media. Deletion of other FDB1 cluster genes, in particular AMD1 and DLH1, did not affect BOA degradation. Phylogenetic analyses and topology testing of the FDB1 and FDB2 cluster genes suggested two horizontal transfer events among fungi, one being transfer of FDB1 from Fusarium to Colletotrichum, and the second being transfer of the FDB2 cluster from Fusarium to Aspergillus. Together, the results suggest that plant-derived xenobiotics have exerted evolutionary pressure on these fungi, leading to horizontal transfer of genes that enhance fitness or virulence. PMID- 26808654 TI - IFP News. PMID- 26808653 TI - "If You Tell People That You Had Sex with a Fellow Man, It Is Hard to Be Helped and Treated": Barriers and Opportunities for Increasing Access to HIV Services among Men Who Have Sex with Men in Uganda. AB - BACKGROUND: Despite the high HIV prevalence among men who have sex with men (MSM) in sub-Saharan Africa, little is known about their access to HIV services. This study assessed barriers and opportunities for expanding access to HIV services among MSM in Uganda. METHODS: In October-December 2013, a cross-sectional qualitative study was conducted in 12 districts of Uganda. Semi-structured in depth interviews were conducted with 85 self-identified MSM by snowball sampling and 61 key informants including HIV service providers and policy makers. Data were analysed using manifest content analysis and Atlas.ti software. RESULTS: Three quarters of the MSM (n = 62, 72.9%) were not comfortable disclosing their sexual orientation to providers and 69 (81.1%) felt providers did not respect MSM. Half (n = 44, 51.8%) experienced difficulties in accessing health services. Nine major barriers to access were identified, including: (i) unwelcoming provider behaviours; (ii) limited provider skills and knowledge; (iii) negative community perceptions towards MSM; (iv) fear of being exposed as MSM; (v) limited access to MSM-specific services; (vi) high mobility of MSM, (vii) lack of guidelines on MSM health services; viii) a harsh legal environment; and ix) HIV related stigma. Two-thirds (n = 56, 66%) participated in MSM social networks and 86% of these (48) received support from the networks to overcome barriers to accessing services. CONCLUSIONS: Negative perceptions among providers and the community present barriers to service access among MSM. Guidelines, provider skills building and use of social networks for mobilization and service delivery could expand access to HIV services among MSM in Uganda. PMID- 26808655 TI - Towards the Development of Structure-Selective G-Quadruplex-Binding Indolo[3,2 b]quinolines. AB - The interaction of phenyl-substituted indolo[3,2-b]quinolines with DNA G quadruplexes of different topology were studied by using a combination of spectroscopic and calorimetric methodologies. N5-Methylated indoloquinoline derivatives ((Me) PIQ) with an aminoalkyl side chain exhibit high affinities for the parallel-stranded MYC quadruplex and a (3+1)-hybrid structure combined with an excellent discrimination against the antiparallel thrombin-binding aptamer (TBA) and the human telomeric (HT) quadruplexes. Dissociation constants for the binding of the ligand to the MYC quadruplex are in the submicromolar range, being below the corresponding dissociation constants for the antiparallel-stranded quadruplexes by about one order of magnitude. Competition experiments with double helical DNA reveal the impact of indoloquinoline structural features on the selectivity for the parallel quadruplex relative to duplex DNA. Based on a calorimetric analysis binding to MYC is shown to be equally driven by favorable enthalpic and entropic contributions with no significant impact on the type of cation present. PMID- 26808656 TI - RNA helicases in bacteria. AB - RNA plays a crucial role in the control of bacterial gene expression, either as carrier of information or as positive or negative regulators. Moreover, the machinery to decode the information, the ribosome, is a large ribonucleoprotein complex composed of rRNAs and many proteins. RNAs are normally single stranded but have the propensity to fold into secondary structures or anneal each other. In some instances these interactions are beneficial for the function of the RNA, but in other cases they may be deleterious. All cells have therefore developed proteins that act as chaperones or helicases to keep RNA metabolism alive. PMID- 26808657 TI - Deprivation of L-Arginine Induces Oxidative Stress Mediated Apoptosis in Leishmania donovani Promastigotes: Contribution of the Polyamine Pathway. AB - The growth and survival of intracellular parasites depends on the availability of extracellular nutrients. Deprivation of nutrients viz glucose or amino acid alters redox balance in mammalian cells as well as some lower organisms. To further understand the relationship, the mechanistic role of L-arginine in regulation of redox mediated survival of Leishmania donovani promastigotes was investigated. L-arginine deprivation from the culture medium was found to inhibit cell growth, reduce proliferation and increase L-arginine uptake. Relative expression of enzymes, involved in L-arginine metabolism, which leads to polyamine and trypanothione biosynthesis, were downregulated causing decreased production of polyamines in L-arginine deprived parasites and cell death. The resultant increase in reactive oxygen species (ROS), due to L-arginine deprivation, correlated with increased NADP+/NADPH ratio, decreased superoxide dismutase (SOD) level, increased lipid peroxidation and reduced thiol content. A deficiency of L-arginine triggered phosphatidyl serine externalization, a change in mitochondrial membrane potential, release of intracellular calcium and cytochrome-c. This finally led to DNA damage in Leishmania promastigotes. In summary, the growth and survival of Leishmania depends on the availability of extracellular L-arginine. In its absence the parasite undergoes ROS mediated, caspase-independent apoptosis-like cell death. Therefore, L-arginine metabolism pathway could be a probable target for controlling the growth of Leishmania parasites and disease pathogenesis. PMID- 26808658 TI - Molecular Identification of Staphylococcus aureus in Airway Samples from Children with Cystic Fibrosis. AB - BACKGROUND: Staphylococcus aureus is a common and significant pathogen in cystic fibrosis. We sought to determine if quantitative PCR (qPCR) and 16S rRNA gene sequencing could provide a rapid, culture-independent approach to the identification of S. aureus airway infections. METHODS: We examined the sensitivity and specificity of two qPCR assays, targeting the femA and 16S rRNA gene, using culture as the gold standard. In addition, 16S rRNA gene sequencing to identify S. aureus directly from airway samples was evaluated. DNA extraction was performed with and without prior enzymatic digestion. RESULTS: 87 samples [42 oropharyngeal (OP) and 45 expectorated sputum (ES)] were analyzed. 59 samples (68%) cultured positive for S. aureus. Using standard extraction techniques, sequencing had the highest sensitivity for S. aureus detection (85%), followed by FemA qPCR (52%) and 16SrRNA qPCR (34%). For all assays, sensitivity was higher from ES samples compared to OP swabs. Specificity of the qPCR assays was 100%, but 21.4% for sequencing due to detection of S. aureus in low relative abundance from culture negative samples. Enzymatic digestion increased the sensitivity of qPCR assays, particularly for OP swabs. CONCLUSION: Sequencing had a high sensitivity for S. aureus, but low specificity. While femA qPCR had higher sensitivity than 16S qPCR for detection of S. aureus, neither assay was as sensitive as sequencing. The significance of S. aureus detection with low relative abundance by sequencing in culture-negative specimens is not clear. PMID- 26808659 TI - Next Generation Sequencing-Based Investigation of Potential Patient-to-Patient Hepatitis C Virus Transmission during Hemodialytic Treatment. AB - We investigated potential patient-to-patient transmission of hepatitis C virus (HCV) in two hemodialysis centers in Beijing, China. Approximately 8.25% (32/388) hemodialysis patients were HCV antibody positive, and 4.90% (19/388) were HCV RNA positive, which consisted of 2a genotype (1/19) and 1b genotypes (18/19). Using next generation sequencing (NGS) approach, MiSeq platform, we sequenced HCV, targeting hypervariable region 1 (263 base-pairs) of genotype 1b specimens and obtained 18 to 243 unique HCV variants. Analysis of phylogenetic tree, viral epidemiology signature pattern (VESP) and Shannon entropy indicated no obvious HCV similarity for most HCV infections but limited HCV variants from Patient 31 (P31) were closer with respect to evolutionary relationship with Patient 24 (P24). However, it was unlikely that HCV was transmitted directly from P24 to P31 in the hemodialysis center. Otherwise, their genetic distance (3.92%-8.92%), would have been much less. Moreover, P31 was infected less than two years before specimen collection, and other external high risk factors existed for these two patients. Thus, our data indicated no evidence of patient-to-patient transmission of HCV in the two hemodialysis centers, suggesting that current HCV infection control measures are effective. PMID- 26808660 TI - Respiratory outcomes after mid-cervical transplantation of embryonic medullary cells in rats with cervical spinal cord injury. AB - Respiratory motor output after cervical spinal cord injury (cSCI) is profoundly influenced by spinal serotonin. We hypothesized that intraspinal transplantation of embryonic midline brainstem (MB) cells rich in serotonergic raphe neurons would improve respiratory outcomes after cSCI. One week after hemisection of the 2nd cervical segment (C2Hx) a suspension of either embryonic (E14) MB cells, fetal spinal cord cells (FSC), or media only (sham) was delivered to the dorsal C3 spinal cord of adult male rats. Six weeks later, ventilation was evaluated using plethysmography; phrenic nerve activity was evaluated in a subset of rats. Seven of 12 rats receiving MB-derived grafts had clear histological evidence of serotonin-positive neurons in the C3-4 dorsal white matter. The transplantations had no impact on baseline breathing patterns, but during a brief respiratory challenge (7% inspired CO2) rats with successful MB grafts had increased ventilation compared to rats with failed MB grafts, FSC or sham grafts. Recordings from the phrenic nerve ipsilateral to C2Hx also indicated increased output during respiratory challenge in rats with successful MB grafts. We conclude that intraspinal allografting of E14 MB cells can have a positive impact on respiratory motor recovery following high cSCI. PMID- 26808661 TI - Analysis of the behavioral, cellular and molecular characteristics of pain in severe rodent spinal cord injury. AB - Human SCI is frequently associated with chronic pain that is severe and refractory to medical therapy. Most rodent models used to assess pain outcomes in SCI apply moderate injuries to lower thoracic spinal levels, whereas the majority of human lesions are severe in degree and occur at cervical or upper thoracic levels. To better model and understand mechanisms associated with chronic pain after SCI, we subjected adult rats to T3 severe compression or complete transection lesions, and examined pain-related behaviors for three months. Within one week after injury, rats developed consistent forepaw pain-related behaviors including increased spontaneous lifts, tactile allodynia and cold sensitivity that persisted for three months. Place escape avoidance testing confirmed that withdrawal of the forepaws from a von Frey stimulus represented active pain related aversion. Spontaneous and evoked pain-related measures were attenuated by gabapentin, further indicating that these behaviors reflect development of pain. Spinal level of injury was relevant: rats with T11 severe SCI did not exhibit forepaw pain-related behaviors. Immunoblotting and immunofluorescence of C6-C8 spinal dorsal horn, reflecting sensory innervation of the forepaw, revealed: 1) expansion of CGRP immunoreactivity in lamina I/II; 2) increased GAP-43 expression; and 3) increased IBA1, GFAP and connexin-43 expression. These findings indicate that aberrant pain fiber sprouting and gliopathy occur after severe SCI. Notably, satellite glial cells (SGCs) in C6-C8 DRGs exhibited increases in GFAP and connexin-43, suggesting ongoing peripheral sensitization. Carbenoxolone, a gap junction inhibitor, and specific peptide inhibitors of connexin-43, ameliorated established tactile allodynia after severe SCI. Collectively, severe T3 SCI successfully models persistent pain states and could constitute a useful model system for examining candidate translational pain therapies after SCI. PMID- 26808662 TI - Reliability and Validity of Dual-Task Mobility Assessments in People with Chronic Stroke. AB - BACKGROUND: The ability to perform a cognitive task while walking simultaneously (dual-tasking) is important in real life. However, the psychometric properties of dual-task walking tests have not been well established in stroke. OBJECTIVE: To assess the test-retest reliability, concurrent and known-groups validity of various dual-task walking tests in people with chronic stroke. DESIGN: Observational measurement study with a test-retest design. METHODS: Eighty-eight individuals with chronic stroke participated. The testing protocol involved four walking tasks (walking forward at self-selected and maximal speed, walking backward at self-selected speed, and crossing over obstacles) performed simultaneously with each of the three attention-demanding tasks (verbal fluency, serial 3 subtractions or carrying a cup of water). For each dual-task condition, the time taken to complete the walking task, the correct response rate (CRR) of the cognitive task, and the dual-task effect (DTE) for the walking time and CRR were calculated. Forty-six of the participants were tested twice within 3-4 days to establish test-retest reliability. RESULTS: The walking time in various dual task assessments demonstrated good to excellent reliability [Intraclass correlation coefficient (ICC2,1) = 0.70-0.93; relative minimal detectable change at 95% confidence level (MDC95%) = 29%-45%]. The reliability of the CRR (ICC2,1 = 0.58-0.81) and the DTE in walking time (ICC2,1 = 0.11-0.80) was more varied. The reliability of the DTE in CRR (ICC2,1 = -0.31-0.40) was poor to fair. The walking time and CRR obtained in various dual-task walking tests were moderately to strongly correlated with those of the dual-task Timed-up-and-Go test, thus demonstrating good concurrent validity. None of the tests could discriminate fallers (those who had sustained at least one fall in the past year) from non fallers. LIMITATION: The results are generalizable to community-dwelling individuals with chronic stroke only. CONCLUSIONS: The walking time derived from the various dual-task assessments generally demonstrated good to excellent reliability, making them potentially useful in clinical practice and future research endeavors. However, the usefulness of these measurements in predicting falls needs to be further explored. Relatively low reliability was shown in the cognitive outcomes and DTE, which may not be preferred measurements for assessing dual-task performance. PMID- 26808663 TI - Call Off the Dog(ma): M1/M2 Polarization Is Concurrent following Traumatic Brain Injury. AB - Following the primary mechanical impact, traumatic brain injury (TBI) induces the simultaneous production of a variety of pro- and anti-inflammatory molecular mediators. Given the variety of cell types and their requisite expression of cognate receptors this creates a highly complex inflammatory milieu. Increasingly in neurotrauma research there has been an effort to define injury-induced inflammatory responses within the context of in vitro defined macrophage polarization phenotypes, known as "M1" and "M2". Herein, we expand upon our previous work in a rodent model of TBI to show that the categorization of inflammatory response cannot be so easily delineated using this nomenclature. Specifically, we show that TBI elicited a wide spectrum of concurrent expression responses within both pro- and anti-inflammatory arms. Moreover, we show that the cells principally responsible for the production of these inflammatory mediators, microglia/macrophages, simultaneously express both "M1" and "M2" phenotypic markers. Overall, these data align with recent reports suggesting that microglia/macrophages cannot adequately switch to a polarized "M1-only" or "M2 only" phenotype, but display a mixed phenotype due to the complex signaling events surrounding them. PMID- 26808664 TI - "Cold training" affects rat liver responses to continuous cold exposure. AB - Continuous exposure of homeothermic animals to low environmental temperatures elicits physiological adaptations necessary for animal survival, which are associated to higher generation of pro-oxidants in thermogenic tissues. It is not known whether intermittent cold exposure (cold training) is able to affect tissue responses to continuous cold exposure. Therefore, we investigated whether rat liver responses to continuous cold exposure of 2 days are modified by cold training (1h daily for 5 days per week for 3 consecutive weeks). Continuous cold increased liver oxidative metabolism by increasing tissue content of mitochondrial proteins and mitochondrial aerobic capacity. Cold training did not affect such parameters, but attenuated or prevented the changes elicited by continuous cold exposure. Two-day cold exposure increased lipid hydroperoxide and protein-bound carbonyl levels in homogenates and mitochondria, whereas cold training decreased such effects although it decreased only homogenate protein damage in control rats. The activities of the antioxidant enzymes GPX and GR and H2O2 production were increased by continuous cold exposure. Despite the increase in GPX and GR activities, livers from cold-exposed rats showed increased susceptibility to in vitro oxidative challenge. Such cold effects were decreased by cold training, which in control rats reduced only H2O2 production and susceptibility to stress. The changes of PGC-1, NRF-1, and NRF-2 expression levels were consistent with those induced by cold exposure and cold training in mitochondrial protein content and antioxidant enzyme activities. However, the mechanisms by which cold training attenuates the effects of the continuous cold exposure remain to be elucidated. PMID- 26808665 TI - Adaptive responses to antibody based therapy. AB - Receptor tyrosine kinases (RTKs) represent a large class of protein kinases that span the cellular membrane. There are 58 human RTKs identified which are grouped into 20 distinct families based upon their ligand binding, sequence homology and structure. They are controlled by ligand binding which activates intrinsic tyrosine-kinase activity. This activity leads to the phosphorylation of distinct tyrosines on the cytoplasmic tail, leading to the activation of cell signaling cascades. These signaling cascades ultimately regulate cellular proliferation, apoptosis, migration, survival and homeostasis of the cell. The vast majority of RTKs have been directly tied to the etiology and progression of cancer. Thus, using antibodies to target RTKs as a cancer therapeutic strategy has been intensely pursued. Although antibodies against the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) have shown promise in the clinical arena, the development of both intrinsic and acquired resistance to antibody-based therapies is now well appreciated. In this review we provide an overview of the RTK family, the biology of EGFR and HER2, as well as an in-depth review of the adaptive responses undertaken by cells in response to antibody based therapies directed against these receptors. A greater understanding of these mechanisms and their relevance in human models will lead to molecular insights in overcoming and circumventing resistance to antibody based therapy. PMID- 26808666 TI - Calcium versus oral contraceptive pills containing drospirenone for the treatment of mild to moderate premenstrual syndrome: a double blind randomized placebo controlled trial. AB - OBJECTIVE: To compare the efficacy of calcium supplements versus combined oral contraceptive pills (COC) containing drospirenone in treating mild to moderate premenstrual syndrome. STUDY DESIGN: This was a double-blind, randomized placebo controlled trial conducted in Beni-Suef University Hospital. Premenstrual syndrome (PMS) was prospectively diagnosed using the Daily Record of Severity of Problems (DRSP). In total, 210 women with mild to moderate PMS were randomly divided into three equal groups. Group 1 received COC daily for 21 days starting on the third day of menstruation and a daily oral placebo similar to calcium and vitamin D. Group 2 received calcium 400mg+vitamin D 400IU once daily and an oral placebo similar to COC for 21 days starting on the third day of menstruation. Group 3 received a daily placebo similar to calcium and vitamin D in addition to an oral placebo similar to COC for 21 days starting on the third day of menstruation. Treatment was continued for 3 months. RESULTS: The proportion of women with improved PMS decreased progressively from the COC group to the calcium group and the placebo group (81%, 62.3% and 16.3%, respectively; p<0.001). Similarly, mean DRSP scores 5 days before menstruation decreased progressively from the COC group, the calcium group and the placebo group (45.51+/-16.97, 55+/ 15.71 and 74.98+/-19.12, respectively; p<0.001). CONCLUSION: Both COC and calcium supplements improved DRSP scores in women with mild to moderate PMS, but the improvement was more evident with COC. PMID- 26808667 TI - Urinary incontinence in primigravida: the neglected pregnancy predicament. AB - OBJECTIVE: To determine the prevalence of urinary incontinence among primigravida in the third trimester, its risk factors and its effect to quality of life. STUDY DESIGN: This is a cross sectional study involving primigravida in their third trimester of pregnancy, who attended the Patient Assessment Centre of a tertiary referral hospital in Klang Valley from July 2012 to June 2013. The participants were chosen randomly using convenience sampling. A face-to-face interview and a review of their antenatal record were done by trained interviewers. Data on sociodemographic and risk factors were obtained followed by the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF). The data was analysed using Statistical Package for Social Science version 20.0. RESULTS: A total of 306 women were involved. The prevalence of urinary incontinence during third trimester was 34.3% (95%CI: 29.0, 39.7). Stress incontinence (64.8%) is the commonest followed by mixed incontinence (24.8%) and urge incontinence (6.7%). Childhood enuresis (p=0.003) and previous history of urinary incontinence (p<0.001) were significantly associated with urinary incontinence. More than 50 percent of women with urinary incontinence in the third trimester felt that it did not affect their daily activities at all. Only 10% of women felt greatly affected by this problem. CONCLUSION: Urinary incontinence is not uncommon among primigravida however many women did not feel that it affected their quality of life. Childhood enuresis and history of urinary incontinence were proven risk factors. PMID- 26808668 TI - Multi-target spectrally resolved fluorescence lifetime imaging microscopy. AB - We introduce a pattern-matching technique for efficient identification of fluorophore ratios in complex multidimensional fluorescence signals using reference fluorescence decay and spectral signature patterns of individual fluorescent probes. Alternating pulsed laser excitation at three different wavelengths and time-resolved detection on 32 spectrally separated detection channels ensures efficient excitation of fluorophores and a maximum gain of fluorescence information. Using spectrally resolved fluorescence lifetime imaging microscopy (sFLIM), we were able to visualize up to nine different target molecules simultaneously in mouse C2C12 cells. By exploiting the sensitivity of fluorescence emission spectra and the lifetime of organic fluorophores on environmental factors, we carried out fluorescence imaging of three different target molecules in human U2OS cells with the same fluorophore. Our results demonstrate that sFLIM can be used for super-resolution multi-target imaging by stimulated emission depletion (STED). PMID- 26808669 TI - A genetically targetable near-infrared photosensitizer. AB - Upon illumination, photosensitizer molecules produce reactive oxygen species that can be used for functional manipulation of living cells, including protein inactivation, targeted-damage introduction and cellular ablation. Photosensitizers used to date have been either exogenous, resulting in delivery and removal challenges, or genetically encoded proteins that form or bind a native photosensitizing molecule, resulting in a constitutively active photosensitizer inside the cell. We describe a genetically encoded fluorogen activating protein (FAP) that binds a heavy atom-substituted fluorogenic dye, forming an 'on-demand' activated photosensitizer that produces singlet oxygen and fluorescence when activated with near-infrared light. This targeted and activated photosensitizer (TAPs) approach enables protein inactivation, targeted cell killing and rapid targeted lineage ablation in living larval and adult zebrafish. The near-infrared excitation and emission of this FAP-TAPs provides a new spectral range for photosensitizer proteins that could be useful for imaging, manipulation and cellular ablation deep within living organisms. PMID- 26808670 TI - Highly multiplexed simultaneous detection of RNAs and proteins in single cells. AB - To enable the detection of expression signatures specific to individual cells, we developed PLAYR (proximity ligation assay for RNA), a method for highly multiplexed transcript quantification by flow and mass cytometry that is compatible with standard antibody staining. When used with mass cytometry, PLAYR allowed for the simultaneous quantification of more than 40 different mRNAs and proteins. In primary cells, we quantified multiple transcripts, with the identity and functional state of each analyzed cell defined on the basis of the expression of a separate set of transcripts or proteins. By expanding high-throughput deep phenotyping of cells beyond protein epitopes to include RNA expression, PLAYR opens a new avenue for the characterization of cellular metabolism. PMID- 26808671 TI - Phenotyping of UGT1A1 Activity Using Raltegravir Predicts Pharmacokinetics and Toxicity of Irinotecan in FOLFIRI. AB - BACKGROUND: Irinotecan toxicity correlates with UGT1A1 activity. We explored whether phenotyping UGT1A1 using a probe approach works better than current genotyping methods. METHODS: Twenty-four Asian cancer patients received irinotecan as part of the FOLFIRI regimen. Subjects took raltegravir 400 mg orally and intravenous midazolam 1 mg. Pharmacokinetic analyses were performed using WinNonLin and NONMEM. Genomic DNA was isolated and screened for the known genetic variants in UGT1A1 and CYP3A4/5. RESULTS: SN-38G/SN-38 AUC ratio correlated well with Raltegravir glucuronide/ Raltegravir AUC ratio (r = 0.784 p<0.01). Midazolam clearance correlated well with irinotecan clearance (r = 0.563 p<0.01). SN-38 AUC correlated well with Log10Nadir Absolute Neutrophil Count (ANC) (r = -0.397 p<0.05). Significant correlation was found between nadir ANC and formation rate constant of raltegravir glucuronide (r = 0.598, P<0.005), but not UGT1A1 genotype. CONCLUSION: Raltegravir glucuronide formation is a good predictor of nadir ANC, and can predict neutropenia in East Asian patients. Prospective studies with dose adjustments should be done to develop raltegravir as a probe to optimize irinotecan therapy. TRIAL REGISTRATION: Clinicaltrials.gov NCT00808184. PMID- 26808673 TI - Improvement of Cycling Performance of Lithium-Sulfur Batteries by Using Magnesium Oxide as a Functional Additive for Trapping Lithium Polysulfide. AB - Trapping lithium polysulfides formed in the sulfur positive electrode of lithium sulfur batteries is one of the promising approaches to overcome the issues related to polysulfide dissolution. In this work, we demonstrate that intrinsically hydrophilic magnesium oxide (MgO) nanoparticles having surface hydroxyl groups can be used as effective additives to trap lithium polysulfides in the positive electrode. MgO nanoparticles were uniformly distributed on the surface of the active sulfur, and the addition of MgO into the sulfur electrode resulted in an increase in capacity retention of the lithium-sulfur cell compared to a cell with pristine sulfur electrode. The improvement in cycling stability was attributed to the strong chemical interactions between MgO and lithium polysulfide species, which suppressed the shuttling effect of lithium polysulfides and enhanced the utilization of the sulfur active material. To the best of our knowledge, this report is the first demonstration of MgO as an effective functional additive to trap lithium polysulfides in lithium-sulfur cells. PMID- 26808672 TI - Presence of Systemic Inflammatory Response Syndrome Predicts a Poor Clinical Outcome in Dogs with a Primary Hepatitis. AB - Primary hepatopathies are a common cause of morbidity and mortality in dogs. The underlying aetiology of most cases of canine hepatitis is unknown. Consequently, treatments are typically palliative and it is difficult to provide accurate prognostic information to owners. In human hepatology there is accumulating data which indicates that the presence of systemic inflammatory response syndrome (SIRS) is a common and debilitating event in patients with liver diseases. For example, the presence of SIRS has been linked to the development of complications such as hepatic encephalopathy (HE) and is associated with a poor clinical outcome in humans with liver diseases. In contrast, the relationship between SIRS and clinical outcome in dogs with a primary hepatitis is unknown. Seventy dogs with histologically confirmed primary hepatitis were enrolled into the study. Additional clinical and clinicopathological information including respiratory rate, heart rate, temperature, white blood cell count, sodium, potassium, sex, presence of ascites, HE score, alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin and red blood cell concentration were available in all cases. The median survival of dogs with a SIRS score of 0 or 1 (SIRS low) was 231 days compared to a median survival of 7 days for dogs with a SIRS score of 2, 3 or 4 (SIRS high) (p<0.001). A Cox proportional hazard model, which included all other co-variables, revealed that a SIRS high score was an independent predictor of a poor clinical outcome. The effect of modulating inflammation on treatment outcomes in dogs with a primary hepatitis is deserving of further study. PMID- 26808674 TI - Child-Report Measures of Occupational Performance: A Systematic Review. AB - INTRODUCTION: Improving occupational performance is a key service of occupational therapists and client-centred approach to care is central to clinical practice. As such it is important to comprehensively evaluate the quality of psychometric properties reported across measures of occupational performance; in order to guide assessment and treatment planning. OBJECTIVE: To systematically review the literature on the psychometric properties of child-report measures of occupational performance for children ages 2-18 years. METHODS: A systematic search of the following six electronic databases was conducted: CINAHL; PsycINFO; EMBASE; PubMed; the Health and Psychosocial Instruments (HAPI) database; and Google Scholar. The quality of the studies was evaluated against the COSMIN taxonomy of measurement properties and the overall quality of psychometric properties was evaluated using pre-set psychometric criteria. RESULTS: Fifteen articles and one manual were reviewed to assess the psychometric properties of the six measures-the PEGS, MMD, CAPE, PAC, COSA, and OSA- which met the inclusion criteria. Most of the measures had conducted good quality studies to evaluate the psychometric properties of measures (PEGS, CAPE, PAC, OSA); however, the quality of the studies for two of these measures was relatively weak (MMD, COSA). When integrating the quality of the psychometric properties of the measures with the quality of the studies, the PAC stood out as having superior psychometric qualities. CONCLUSIONS: The overall quality of the psychometric properties of most measures was limited. There is a need for continuing research into the psychometric properties of child-report measures of occupational performance, and to revise and improve the psychometric properties of existing measures. PMID- 26808675 TI - White matter volume in the brainstem and inferior parietal lobule is related to motor performance in children with autism spectrum disorder: A voxel-based morphometry study. AB - Many studies have reported poor motor performance in autism spectrum disorder (ASD); however, the underlying brain mechanisms remain unclear. Recent neuroimaging studies have suggested that abnormalities of the white matter (WM) are related to the features of ASD. In this study, we used voxel-based morphometry (VBM) to investigate which WM regions correlate with motor performance in children with ASD, and whether the WM volume in those brain regions differed between children with ASD and typically developing (TD) children. The subjects included 19 children with ASD and 20 TD controls. Motor performance was assessed using the Movement Assessment Battery for Children 2 (M ABC 2). Children with ASD showed poorer motor performance than did the controls. There was a significant positive correlation between the total test score on the M-ABC 2 and the volume of WM in the brainstem and WM adjacent to the left supramarginal gyrus (SMG). In addition, compared with the TD controls, children with ASD had a decreased volume of WM in the brainstem and adjacent to the left intraparietal sulcus, which is close to the SMG. These findings suggest that structural changes in the WM in the brainstem and left inferior parietal lobule may contribute to poor motor performance in children with ASD. Autism Res 2016, 9: 981-992. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 26808676 TI - Kinetics of the early development of uniparental human haploid embryos. AB - OBJECTIVE: To describe morphokinetically the early development of human haploid parthenotes and androgenotes and to compare them with euploid embryos. DESIGN: Experimental study of kinetics. SETTING: University-affiliated private fertility center. PATIENT(S): Experimental haploid parthenotes and androgenotes. INTERVENTION(S): Kinetic study of early development (up to eight cells) of 8 parthenotes, 10 androgenotes, and 20 euploid embryos. MAIN OUTCOME MEASURE(S): Timing of the first seven cleavages determined according to embryo origin, then calculation of the duration of the second and third cell cycles (cc2 and cc3) of whole embryos and individual cells. RESULT(S): Parthenotes and androgenotes were experimentally produced by artificial oocyte activation and intracytoplasmic sperm injection of enucleated oocytes, respectively. Uniparental embryos having 6 to 10 cells were assessed for haploidy, their kinetics analyzed, retrospectively compared with euploid embryos. All the first seven cleavages occurred later in parthenotes than in both androgenotes and correctly fertilized embryos. The whole embryos and single cells showed that cc2 was longer in parthenotes than in both androgenotes and correctly fertilized embryos; cc3 was shorter in androgenotes than in both parthenotes and correctly fertilized embryos. The duration of cc2 versus cc3 was longer in correctly fertilized embryos and parthenotes than in androgenotes. CONCLUSION(S): Parthenotes and androgenotes have different kinetics. The former have a longer cc2, and the latter a consistently shorter cc3 in comparison with correctly fertilized embryos. PMID- 26808677 TI - Translational Control of UIS4 Protein of the Host-Parasite Interface Is Mediated by the RNA Binding Protein Puf2 in Plasmodium berghei Sporozoites. AB - UIS4 is a key protein component of the host-parasite interface in the liver stage of the rodent malaria parasite Plasmodium berghei and required for parasite survival after invasion. In the infectious sporozoite, UIS4 protein has variably been shown to be translated but also been reported to be translationally repressed. Here we show that uis4 mRNA translation is regulated by the P. berghei RNA binding protein Pumilio-2 (PbPuf2 or Puf2 from here on forward) in infectious salivary gland sporozoites in the mosquito vector. Using RNA immunoprecipitation we show that uis4 mRNA is bound by Puf2 in salivary gland sporozoites. In the absence of Puf2, uis4 mRNA translation is de-regulated and UIS4 protein expression upregulated in salivary gland sporozoites. Here, using RNA immunoprecipitation, we reveal the first Puf2-regulated mRNA in this parasite. PMID- 26808679 TI - Interhemispheric Lipoma, Callosal Anomaly, and Malformations of Cortical Development: A Case Series. AB - Intracranial lipomas are rare congenital malformations. The most common type of intracranial lipoma is the interhemispheric lipoma, which is frequently associated with callosal anomalies such as hypogenesis or agenesis of the corpus callosum. In contrast, interhemispheric lipomas are less often accompanied with malformations of cortical development (MCD). We report magnetic resonance imaging findings of three infants with an interhemispheric lipoma, associated with a callosal anomaly, and MCD: two infants with nodular interhemispheric lipoma, agenesis of the corpus callosum, and polymicrogyria, and one infant with interhemispheric curvilinear lipoma, hypoplasia of the corpus callosum, and heterotopias. An association was suggested regarding the occurrence of these malformations. PMID- 26808678 TI - Impact of Triple Therapy in Elderly Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention. AB - BACKGROUND AND PURPOSE: Selecting an ideal antithrombotic therapy for elderly patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) can be challenging since they have a higher thromboembolic and bleeding risk than younger patients. The current study aimed to assess the efficacy and safety of triple therapy (TT: oral anticoagulation plus dual antiplatelet therapy: aspirin plus clopidogrel) in patients >=75 years of age with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). METHODS: A prospective multicenter study was conducted from 2003 to 2012 at 6 Spanish teaching hospitals. A cohort study of consecutive patients with AF undergoing PCI and treated with TT or dual antiplatelet therapy (DAPT) was analyzed. All outcomes were evaluated at 1-year of follow-up. RESULTS: Five hundred and eighty-five patients, 289 (49%) of whom were >=75 years of age (79.6+/-3.4 years; 33% women) were identified. TT was prescribed in 55.9% of patients at discharge who had a higher thromboembolic risk (CHA2DS2VASc score: 4.23+/-1.51 vs 3.76+/-1.40, p = 0.007 and a higher bleeding risk (HAS-BLED >=3: 88.6% vs 79.2%, p = 0.02) than those on DAPT. Therefore, patients on TT had a lower rate of thromboembolism than those on DAPT (0.6% vs 6.9%, p = 0.004; HR 0.08, 95% CI: 0.01-0.70, p = 0.004). Major bleeding events occurred more frequently in patients on TT than in those on DAPT (11.7% vs 2.4%, p = 0.002; HR 5.2, 95% CI: 1.53-17.57, p = 0.008). The overall mortality rate was similar in both treatment groups (11.9% vs 13.9%, p = 0.38); however, after adjustment for confounding variables, TT was associated with a reduced mortality rate (HR 0.33, 95% CI: 0.12-0.86, p = 0.02). CONCLUSIONS: In elderly patients with AF undergoing PCI, the use of TT compared to DAPT was associated with reduced thromboembolism and mortality rates, although a higher rate of major bleeding. PMID- 26808680 TI - Determination of Glyphosate Levels in Breast Milk Samples from Germany by LC MS/MS and GC-MS/MS. AB - This study describes the validation and application of two independent analytical methods for the determination of glyphosate in breast milk. They are based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography tandem mass spectrometry (GC-MS/MS), respectively. For LC-MS/MS, sample preparation involved an ultrafiltration followed by chromatography on an anion exchange column. The analysis by GC-MS/MS involved an extraction step, cleanup on a cation exchange column, and derivatization with heptafluorobutanol and trifluoroacetic acid anhydride. Both methods were newly developed for breast milk and are able to quantify glyphosate residues at concentrations as low as 1 ng/mL. The methods were applied to quantify glyphosate levels in 114 breast milk samples, which had been collected from August to September of 2015 in Germany. The mothers participated at their own request and thus do not form a representative sample. In none of the investigated samples were glyphosate residues above the limit of detection found. PMID- 26808682 TI - Effects of Arrangement of UV Light-Emitting Diodes on the Inactivation Efficiency of Microorganisms in Water. AB - Ultraviolet light-emitting diodes (UV-LEDs) offer high flexibility in the reactor design for water disinfection. To specify the key design factors affecting the performance of a reactor, we examined how the arrangement of UV-LEDs in a cylindrical reactor affects the inactivation efficiency of Escherichia coli and coliphage Qbeta. A ring-shaped UV-LED apparatus, composed of two units containing ten 285-nm UV-LEDs each, were attached to a quartz cylinder, and microbial suspensions flowed through the cylinder for single pass at altered flow rates. The distance between the two units, L, was altered to examine its effects on inactivation efficiencies. Over 4 log inactivation of E. coli was achieved at 800 mL min-1 regardless of the L values, suggesting that the apparatus has a high potential to disinfect water. The inactivation at L = 20 mm was significantly higher than that at L = 0 in all cases tested (ANOVA, P < 0.05), while this was not true when L was extended to 40 and 60 mm. Therefore, a separate arrangement of UV-LEDs at a certain distance can improve the efficiency, and the distance matters to enhance the performance. This study involves a design concept on how to arrange UV-LEDs in a water disinfection apparatus. PMID- 26808681 TI - Depressed Hypoxic and Hypercapnic Ventilatory Responses at Early Stage of Lethal Avian Influenza A Virus Infection in Mice. AB - H5N1 virus infection results in ~60% mortality in patients primarily due to respiratory failure, but the underlying causes of mortality are unclear. The goal of this study is to reveal respiratory disorders occurring at the early stage of infection that may be responsible for subsequent respiratory failure and death. BALB/c mice were intranasally infected with one of two H5N1 virus strains: HK483 (lethal) or HK486 (non-lethal) virus. Pulmonary ventilation and the responses to hypoxia (HVR; 7% O2 for 3 min) and hypercapnia (HCVR; 7% CO2 for 5 min) were measured daily at 2 days prior and 1, 2, and 3 days postinfection (dpi) and compared to mortality typically by 8 dpi. At 1, 2, and 3 dpi, immunoreactivities (IR) of substance P (SP-IR) in the nodose ganglion or tyrosine hydroxylase (TH IR) in the carotid body coupled with the nucleoprotein of influenza A (NP-IR) was examined in some mice, while arterial blood was collected in others. Our results showed that at 2 and 3 dpi: 1) both viral infections failed to alter body temperature and weight, [Formula: see text], or induce viremia while producing similarly high lung viral titers; 2) HK483, but not HK486, virus induced tachypnea and depressed HVR and HCVR without changes in arterial blood pH and gases; and 3) only HK483 virus led to NP-IR in vagal SP-IR neurons, but not in the carotid body, and increased density of vagal SP-IR neurons. In addition, all HK483, rather than HK486, mice died at 6 to 8 dpi and the earlier death was correlated with more severe depression of HVR and HCVR. Our data suggest that tachypnea and depressed HVR/HCVR occur at the early stage of lethal H5N1 viral infection associated with viral replication and increased SP-IR density in vagal neurons, which may contribute to the respiratory failure and death. PMID- 26808683 TI - Parting Thoughts of a State Health Official. PMID- 26808684 TI - Charting a New Path: Helping Local Health Departments Navigate Emerging Issues in Public Health. PMID- 26808685 TI - Cross-Jurisdictional Resource Sharing in Changing Public Health Landscape: Contributory Factors and Theoretical Explanations. AB - BACKGROUND: Local health departments (LHDs) are striving to meet public health needs within their jurisdictions, amidst fiscal restraints and complex dynamic environment. Resource sharing across jurisdictions is a critical opportunity for LHDs to continue to enhance effectiveness and increase efficiency. PURPOSE: This research examines the extent of cross-jurisdictional resource sharing among LHDs, the programmatic areas and organizational functions for which LHDs share resources, and LHD characteristics associated with resource sharing. METHODS: Data from the National Association of County & City Health Officials' 2013 National Profile of LHDs were used. Descriptive statistics and multinomial logistic regression were performed for the 5 implementation-oriented outcome variables of interest, with 3 levels of implementation. RESULTS: More than 54% of LHDs shared resources such as funding, staff, or equipment with 1 or more other LHDs on a continuous, recurring basis. Results from the multinomial regression analysis indicate that economies of scale (population size and metropolitan status) had significant positive influences (at P <= .05) on resource sharing. Engagement in accreditation, community health assessment, community health improvement planning, quality improvement, and use of the Community Guide were associated with lower levels of engagement in resource sharing. Doctoral degree of the top executive and having 1 or more local boards of health carried a positive influence on resource sharing. CONCLUSIONS: Cross-jurisdictional resource sharing is a viable and commonly used process to overcome the challenges of new and emerging public health problems within the constraints of restricted budgets. LHDs, particularly smaller LHDs with limited resources, should consider increased resource sharing to address emerging challenges. PMID- 26808687 TI - Hierarchical chrysanthemum-flower-like carbon nanomaterials grown by chemical vapor deposition. AB - Novel hierarchical chrysanthemum-flower-like carbon nanomaterials (CFL-CNMs) were synthesized by thermal chemical vapor deposition based on acetylene decomposition. A scanning electron microscope and a transmission electron microscope were employed to observe the morphology and structure of the unconventional nanostructures. It is found that the CFL-CNMs look like a blooming chrysanthemum with a stem rather than a spherical flower. The carbon flower has an average diameter of 5 MUm, an average stem diameter of 150 nm, branch diameters ranging from 20 to 70 nm, and branch lengths ranging from 0.5 to 3 MUm. The morphologies of the CFL-CNMs are unlike any of those previously reported. Fishbone-like carbon nanofibers with a spindle-shaped catalyst locating at the tip can also be found. Furthermore, the catalyst split was proposed to elucidate the formation mechanism of CFL-CNMs. A large and glomerate catalyst particle at the tip of the carbon nanofiber splits into smaller catalyst particles which are catalytic-active points for branch formation, resulting in the formation of CFL CNMs. PMID- 26808688 TI - A randomized, double-blind, placebo-controlled study of escitalopram in patients with social anxiety disorder in Japan. AB - OBJECTIVE: This randomized, double-blind placebo-controlled study compared the efficacy and tolerability of escitalopram (10 and 20 mg/day) in Japanese patients with social anxiety disorder (SAD). RESEARCH DESIGN AND METHODS: Patients aged 18 64 years with a primary diagnosis of DSM-IV-TR defined SAD, a Liebowitz Social Anxiety Scale Japanese version (LSAS-J) total score >=60 and a Clinical Global Impression-Severity (CGI-S) score >=4 at baseline were randomly assigned (1:1:1) to placebo, escitalopram 10 mg or escitalopram 20 mg. The primary endpoint was change from baseline to Week 12 in the LSAS-J total score for both escitalopram 10 mg and 20 mg versus placebo (ANCOVA, FAS, LOCF), using a hierarchical testing procedure. Pre-specified secondary endpoints included LSAS-J sensitivity analyses. CLINICAL TRIAL REGISTRATION: This study has the www.japic.or.jp identifier: JapicCTI-121842. RESULTS: For the primary efficacy endpoint, the difference from placebo in the LSAS-J was -3.9 (p = 0.089) for escitalopram 10 mg. Since the superiority of escitalopram 10 mg over placebo was not confirmed, an analysis without multiplicity adjustment was made, which showed a difference for escitalopram 20 mg versus placebo of -9.8 (p < 0.001). In pre-specified sensitivity analyses, the difference versus placebo was -4.9 (p = 0.035) (ANCOVA, FAS, OC) and -5.0 (p = 0.028) (MMRM, FAS) (escitalopram 10 mg) and -10.1 (p < 0.001) (ANCOVA, FAS, OC) and -10.6 (p < 0.001) (MMRM, FAS) (escitalopram 20 mg). Common adverse events (incidence >=5% and significantly different from placebo) were somnolence, nausea and ejaculation disorder. CONCLUSION: Escitalopram was efficacious, safe and well tolerated by patients with SAD in Japan. Study limitations are discussed including patient characteristics. PMID- 26808689 TI - Modulation of mGlu2 Receptors, but Not PDE10A Inhibition Normalizes Pharmacologically-Induced Deviance in Auditory Evoked Potentials and Oscillations in Conscious Rats. AB - Improvement of cognitive impairments represents a high medical need in the development of new antipsychotics. Aberrant EEG gamma oscillations and reductions in the P1/N1 complex peak amplitude of the auditory evoked potential (AEP) are neurophysiological biomarkers for schizophrenia that indicate disruption in sensory information processing. Inhibition of phosphodiesterase (i.e. PDE10A) and activation of metabotropic glutamate receptor (mGluR2) signaling are believed to provide antipsychotic efficacy in schizophrenia, but it is unclear whether this occurs with cognition-enhancing potential. The present study used the auditory paired click paradigm in passive awake Sprague Dawley rats to 1) model disruption of AEP waveforms and oscillations as observed in schizophrenia by peripheral administration of amphetamine and the N-methyl-D-aspartate (NMDA) antagonist phencyclidine (PCP); 2) confirm the potential of the antipsychotics risperidone and olanzapine to attenuate these disruptions; 3) evaluate the potential of mGluR2 agonist LY404039 and PDE10 inhibitor PQ-10 to improve AEP deficits in both the amphetamine and PCP models. PCP and amphetamine disrupted auditory information processing to the first click, associated with suppression of the P1/N1 complex peak amplitude, and increased cortical gamma oscillations. Risperidone and olanzapine normalized PCP and amphetamine-induced abnormalities in AEP waveforms and aberrant gamma/alpha oscillations, respectively. LY404039 increased P1/N1 complex peak amplitudes and potently attenuated the disruptive effects of both PCP and amphetamine on AEPs amplitudes and oscillations. However, PQ-10 failed to show such effect in either models. These outcomes indicate that modulation of the mGluR2 results in effective restoration of abnormalities in AEP components in two widely used animal models of psychosis, whereas PDE10A inhibition does not. PMID- 26808691 TI - Oriented Nano-Microstructure-Assisted Controllable Fabrication of Metal-Organic Framework Membranes on Nickel Foam. AB - Oriented nano-microstructure-assisted controllable fabrication, a facile and versatile preparation strategy, is developed to fabricate metal-organic framework (MOF) membranes. With this method, several MOF membranes with tailored structures are prepared, including HKUST-1 (with 3D pores) and M3 (HCOO)6 (with 1D pores; M = Co, Mn, and Mg) membranes, which demonstrate good performances in gas separations. PMID- 26808690 TI - Hepatic Deficiency of Augmenter of Liver Regeneration Exacerbates Alcohol-Induced Liver Injury and Promotes Fibrosis in Mice. AB - Why only a subpopulation (about 15%) of humans develops liver cirrhosis due to alcohol is a critical as yet unanswered question. Liver-specific depletion of augmenter of liver regeneration (ALR) protein in mice causes robust steatosis and hepatocyte apoptosis by 2 weeks; these pathologies regress subsequently with return of ALR expression even at lower than control levels, but the mice develop modest steatohepatitis by 8 weeks. We aimed to investigate whether chronic alcohol ingestion promotes excessive hepatic fibrosis in these ALR-deficient mice. Liver-specific ALR-deficient and wild type (WT) female mice (8-10 weeks old) were placed on 4% alcohol-supplemented or isocaloric diet for 4 weeks. Liver sections were examined for histopathology, and parameters of steatosis and fibrosis were quantified. The mRNA expression of alcohol dehydrogenase-1, acetaldehyde dehydrogenase-1 and cytochrome P450-2E1 increased in WT mice but decreased in ALR-deficient mice upon alcohol ingestion. While alcohol induced steatosis and mild inflammation in WT mice, ALR-deficient mice showed minimal steatosis, strong hepatocellular injury and inflammation, prominent ductular proliferation, and robust fibrosis. Compared to the WT mice, alcohol feeding of ALR-deficient mice resulted in significantly greater increase in hepatic TNFalpha and TGFbeta, and oxidative stress; there was also hepatic iron accumulation, robust lipid peroxidation and mitochondrial DNA damage. Importantly, similar to ALR-deficient mice, lower hepatic ALR levels in human alcoholic liver cirrhosis were associated with increased iron content, reduced expression of alcohol dehydrogenase and acetaldehyde dehydrogenase, and elevated fibrogenic markers. We conclude that ALR deficiency or anomaly can play a critical role in alcohol induced hepatic fibrosis/cirrhosis, mechanisms of which may involve dysregulation of alcohol metabolism and iron homeostasis, mitochondrial damage and oxidative injury. PMID- 26808692 TI - Implications of the inflammatory response for the identification of biomarkers of chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is characterized by both local and systemic inflammation. Because inflammation plays a critical role in the development, course and severity of COPD, inflammatory markers have the potential to improve the current diagnostic and prognostic approaches. Local inflammation in COPD is characterized by an infiltration of inflammatory cells, with an increased expression of cytokines, chemokines, enzymes, growth factors and adhesion molecules. Systemic low-grade inflammation is another common but nonspecific finding in COPD. Exacerbations of COPD are acute clinical events accompanied by an exaggerated inflammatory response. Future investigations in the field of COPD biomarkers should take into account different study designs and biochemical assays, disease course and duration, variations in symptom severity and timing of measurement. PMID- 26808694 TI - Serum endothelial cell specific molecule-1 (endocan) levels in patients with obstructive sleep apnea. AB - OBJECTIVE: To investigate the level of endothelial cell specific molecule-1 (endocan) in obstructive sleep apnea (OSA). METHODS: Study group included subjects with OSA. Control group included subjects who had no OSA on polysomnography and nonobese healthy subjects from population who had no OSA symptoms. Endocan levels of OSA and non-OSA subjects were compared. RESULTS: Totally 106 individuals (63 OSA, 43 non-OSA) were included. Endocan levels were higher in OSA subjects than controls (1.25 +/- 0.4 ng/ml vs 0.93 +/- 0.3 ng/ml, p < 0.001). Endocan levels were correlated with BMI (r = 0.456, p < 0.001) and daytime PaO2 (r = -0.266, p < 0.042). In linear regression analysis there was no factor related to endocan level. CONCLUSION: Serum endocan is significantly higher in OSA. Further studies should be performed to better understand the relationship between endocan and OSA. PMID- 26808695 TI - Evaluation of the Performance of the B3LYP, PBE0, and M06 DFT Functionals, and DBLOC-Corrected Versions, in the Calculation of Redox Potentials and Spin Splittings for Transition Metal Containing Systems. AB - We have evaluated the performance of the M06 and PBE0 functionals in their ability to calculate spin splittings and redox potentials for octahedral complexes containing a first transition metal series atom. The mean unsigned errors (MUEs) for these two functionals are similar to those obtained for B3LYP using the same data sets. We then apply our localized orbital correction approach for transition metals, DBLOC, in an effort to improve the results obtained with both functionals. The PBE0-DBLOC results are remarkably close in both MUE and parameter values to those obtained for the B3LYP-DBLOC method. The M06-DBLOC results are less accurate, but the parameter values and trends are still qualitatively very similar. These results demonstrate that DBLOC corrected methods are substantially more accurate for these systems than any of the uncorrected functionals we have tested and that the deviations between hybrid DFT methods and experiment for transition metal containing systems exhibit striking physically based regularities which are very similar for the three functionals that we have examined, despite significant differences in the details of each model. PMID- 26808693 TI - Polyunsaturated lysophosphatidic acid as a potential asthma biomarker. AB - Lysophosphatidic acid (LPA), a lipid mediator in biological fluids and tissues, is generated mainly by autotaxin that hydrolyzes lysophosphatidylcholine to LPA and choline. Total LPA levels are increased in bronchoalveolar lavage fluid from asthmatic lung, and are strongly induced following subsegmental bronchoprovocation with allergen in subjects with allergic asthma. Polyunsaturated molecular species of LPA (C22:5 and C22:6) are selectively synthesized in the airways of asthma subjects following allergen challenge and in mouse models of allergic airway inflammation, having been identified and quantified by LC/MS/MS lipidomics. This review discusses current knowledge of LPA production in asthmatic lung and the potential utility of polyunsaturated LPA molecular species as novel biomarkers in bronchoalveolar lavage fluid and exhaled breath condensate of asthma subjects. PMID- 26808696 TI - Age-related differences of neural connectivity during mental rotation. AB - The purpose of the present study was to investigate age-related effects on functional brain networks during a mental rotation task. At behavioral level age related cognitive deficits have been shown. Cognitive deficits in older adults are associated with structural decline, especially in frontal and parietal areas and in the corpus callosum. In consequence, functional networks are affected by old age as well. To this end, a graph theoretical approach was taken, which quantifies the global and local efficiency as well as the cost efficiency of frontal and parietal intrahemispheric and interhemispheric networks. Main results indicate that intrahemispheric and interhemispheric networks are differently affected by older age: in the left frontal and the left and right parietal intrahemispheric networks global and local efficiency was reduced, whereas in frontal and parietal interhemispheric networks cost efficiency was decreased. PMID- 26808697 TI - Respiratory hypoalgesia? Breath-holding, but not respiratory phase modulates nociceptive flexion reflex and pain intensity. AB - Several observations suggest that respiratory phase (inhalation vs. exhalation) and post-inspiratory breath-holds could modulate pain and the nociceptive reflex. This experiment aimed to investigate the role of both mechanisms. Thirty-two healthy participants received supra-threshold electrocutaneous stimulations to elicit both the Nociceptive Flexion Reflex (NFR) and pain, either during spontaneous inhalations or exhalations, or during three types of instructed breath-holds: following exhalation, at mid-inhalation and at full-capacity inhalation. Whether the electrocutaneous stimulus was applied during inhalation or exhalation did not affect the NFR or pain. Self-reported pain was reduced and the NFR was increased during breath-holding compared to spontaneous breathing. Whereas the type of breath-hold did not impact on self-reported pain, breath holds at full-capacity inhalation and following exhalation were associated with a lower NFR amplitude compared to breath-holds at mid-inhalation. The present findings confirm that breath-holding can modulate pain (sensitivity) and suggest that both attentional distraction and changes in vagal activity may underlie the observed effects. PMID- 26808698 TI - Improved Vision and Contact Lens Wear Time With Piggy-Back Contact Lens Systems in Children After Penetrating Corneal Trauma. AB - OBJECTIVE: Consecutive case series of children treated successfully with "piggy back" (PB) contact lens systems after corneal trauma. METHODS: We reviewed the medical record of all children ages 4 to 14 years treated at the Emory Eye Center between January 11, 2003 and January 11, 2013 with PB contact lens systems. RESULTS: Four children with a history of corneal penetrating trauma were treated with a PB lens system, with a mean age of 7+/-0.08 (range: 6-8) years. Best corrected spectacle vision was count fingers in two children and logMAR +0.70 (Snellen equivalent 20/100) and logMAR +0.6 (Snellen equivalent 20/80) in the remaining two. The PB lens system was introduced with a mean of 15.7+/-6.5 (range: 9-22) months after the injury. All patients were initially fitted with gas-permeable (GP) lenses. Each child achieved 11 or more hours of daily contact lens wear time in PB systems. The mean best-corrected logMAR visual acuity using the PB system was 0.26+/-0.21 (Snellen equivalent 20/36). The mean improvement in best-corrected logMAR between GP and PB lens systems was +0.21+/-0.11, which corresponds to an improvement of greater than two lines on the Snellen chart. CONCLUSION: Piggy-back contact lens systems can be helpful to improve vision and contact lens wearing time in children with irregular astigmatism after corneal trauma, who are intolerant of GP contact lenses. PMID- 26808699 TI - Changes in Peripheral Refraction, Higher-Order Aberrations, and Accommodative Lag With a Radial Refractive Gradient Contact Lens in Young Myopes. AB - PURPOSE: To evaluate changes in the peripheral refraction (PR), visual quality, and accommodative lag with a novel soft radial refractive gradient (SRRG) experimental contact lens that produces peripheral myopic defocus. METHODS: 59 myopic right eyes were fitted with the lens. The PR was measured up to 30 degrees in the nasal and temporal horizontal visual fields and compared with values obtained without the lens. The accommodative lag was measured monocularly using the distance-induced condition method at 40 cm, and the higher-order aberrations (HOAs) of the entire eye were obtained for 3- and 5-mm pupils by aberrometry. Visual performance was assessed through contrast sensitivity function (CSF). RESULTS: With the lens, the relative PR became significantly less hyperopic from 30 degrees to 15 degrees temporally and 30 degrees nasally in the M and J0 refractive components (P<0.05). Cylinder foci showed significant myopization from 30 degrees to 15 degrees temporally and 30 degrees to 25 degrees nasally (P<0.05). The HOAs increased significantly, the CSF decreased slightly but reached statistical significance for 6 and 12 cycles per degree (P<0.05), and the accommodative lag decreased significantly with the SRRG lens (P=0.0001). There was a moderate correlation between HOAs and CSF at medium and high spatial frequencies. CONCLUSION: The SRRG lens induced a significant change in PR, particularly in the temporal retina. Tangential and sagittal foci changed significantly in the peripheral nasal and temporal retina. The decreased accommodative lag and increased HOAs particularly in coma-like aberration may positively affect myopia control. A longitudinal study is needed to confirm this potential. PMID- 26808700 TI - Contact Lens-Induced Discomfort and Inflammatory Mediator Changes in Tears. AB - PURPOSE: Studies indicate that contact lens (CL) discontinuation mostly occurs because of dryness and discomfort symptoms. This study aimed to investigate relationships between changes in the concentration of tear inflammatory mediators with subjective comfort ratings with CL wear and no contact lens wear between morning and evening. METHOD: Forty-five subjects collected tears twice daily in the morning and in the evening with or without lenses. Comfort was rated subjectively on a scale from 1 to 100 (where 100 was extremely comfortable) just before each tear collection. Tear samples were assayed for complement components (C3 and C3a), leukotriene B4 (LTB4), secretory phospholipase A2 (sPLA2), secretory immunoglobulin A (sIgA), and bradykinin using commercially available immuno-based assay kits. RESULTS: Comfort ratings showed a statistically significant decline from morning to evening both with CL (89.0+/-10.1 AM vs. 76.7+/-15.2 PM; P<0.001) and without CL (89.1+/-10.2 AM vs. 84.2+/-12.6 PM; P<0.005) wear. The decline was steeper with lens wear (P<0.001). Bradykinin and sPLA2 levels did not change between morning and evening or with CL wear (P>0.05). Leukotriene B4 levels were slightly higher in CL (CL 43.4+/-12.6 pg/ml vs. No CL 39.4+/-13.4 pg/mL; P=0.034), whereas the concentration of LTB4, C3, C3a, and sIgA dropped by the end of the day in the presence or absence of lens wear (P<0.001). For most mediators, tear levels were not correlated with comfort ratings in any of the conditions. Leukotriene B4 had a higher concentration in the evening, and when measured as a ratio to sIgA, there was a trend for increased concentration of this mediator during CL wear. CONCLUSION: Although specific mediators showed changes from morning to evening with and without lens wear, most of these were not correlated with subjective comfort ratings in lens wear. The only mediator that showed an increase in concentration during the day and during lens wear was LTB4, and further studies on this mediator are warranted. PMID- 26808701 TI - Comparative Evaluation of Use of 400-MUm and 350-MUm Microkeratome Head to Prepare Donor Tissue in Cases of Descemet Stripping Automated Endothelial Keratoplasty. AB - PURPOSE: To compare the outcomes of 400-MUm microkeratome head with 350-MUm microkeratome head Descemet stripping automated endothelial keratoplasty (DSAEK) in a prospective comparative study. METHODS: Twenty cases of pseudophakic bullous keratopathy were randomly allocated into two groups. Group 1 underwent slow, single-pass 400-MUm microkeratome head, whereas group 2 underwent the standard technique of DSAEK using a 350-MUm microkeratome head. The primary outcome measures were best-corrected visual acuity (BCVA) at 6 months. RESULTS: Groups were comparable in baseline characteristics. The mean central graft thickness (GT) at 6 months in group 1 was significantly thinner than group 2 (90.44+/-28.67 vs. 165.60+/-62.74 MUm; P=0.003). The BCVA and contrast sensitivity were significantly better in group 1 than in group 2 (BCVA: 0.34+/-0.15 vs. 0.53+/ 0.19 logMAR units, P=0.02; contrast sensitivity: 1.48+/-0.13 vs. 1.06+/-0.22, P=0.001). A significant correlation was found between both postoperative BCVA and contrast sensitivity, with the postoperative GT using Spearman rho correlation analysis (R=0.534, P=0.01 for BCVA and R=-0.522, P=0.02 for contrast sensitivity). The percentage endothelial cell loss was comparable between the 2 groups at the last follow-up (P=0.3). No major complications were observed during the study period. CONCLUSIONS: The use of a 400-MUm microkeratome head instead of 350-MUm head can improve the visual outcomes in DSAEK without increasing the risk of complications. The thickness of the DSAEK graft can affect the visual acuity and contrast sensitivity. PMID- 26808702 TI - Optimising organs for transplantation: is normothermic machine perfusion the answer? PMID- 26808703 TI - VisBOL: Web-Based Tools for Synthetic Biology Design Visualization. AB - VisBOL is a Web-based application that allows the rendering of genetic circuit designs, enabling synthetic biologists to visually convey designs in SBOL visual format. VisBOL designs can be exported to formats including PNG and SVG images to be embedded in Web pages, presentations and publications. The VisBOL tool enables the automated generation of visualizations from designs specified using the Synthetic Biology Open Language (SBOL) version 2.0, as well as a range of well known bioinformatics formats including GenBank and Pigeoncad notation. VisBOL is provided both as a user accessible Web site and as an open-source (BSD) JavaScript library that can be used to embed diagrams within other content and software. PMID- 26808704 TI - Hydrogen sulfide in hypertension. AB - PURPOSE OF REVIEW: Hypertension is an important determinant of cardiovascular disease, and strict blood pressure regulation is beneficially associated with the risk for cardiovascular events or all-cause mortality. However, intensive antihypertensive treatment is not always sufficient to reach normotension. Hydrogen sulfide (H2S) is a gaseous signalling molecule with antihypertensive properties. It is endogenously produced, but can also be exogenously administrated. The current review provides an overview on H2S research performed in the context of hypertension and cardiovascular disease. RECENT FINDINGS: H2S has been increasingly found to contribute to different (patho-)physiological processes such as blood pressure regulation and scavenging of reactive oxygen species. A deficiency of H2S-producing enzymes results in hypertension, and administration of H2S donors lowers blood pressure and protects against organ damage in the experimental setting. Thiosulfate, a H2S metabolite, can act as a H2S donor, and is already clinically used for the treatment of calciphylaxis in patients with end-stage renal disease. Treatment of hypertensive rats with thiosulfate results in lower blood pressure and reduces organ damage. SUMMARY: Although human data on H2S and hypertension are scarce, experimental data indicate that elevation of H2S levels using dietary sulfate or exogenous H2S (donors) could be a promising therapeutic strategy in the setting of hypertension. PMID- 26808705 TI - Potential role of sodium glucose cotransporter 2 inhibitors in the treatment of hypertension. AB - PURPOSE OF REVIEW: The majority of patients with type 2 diabetes mellitus (T2DM) have hypertension requiring combination therapy. Sodium glucose cotransporter 2 (SGLT2) inhibitors are novel glucose-lowering drugs with shared and potentially unique beneficial effects on cardiovascular risk beyond glycemic control. This review focuses on the potential role of SGLT2 inhibitors in the treatment of hypertension associated with T2DM. RECENT FINDINGS: SGLT2 inhibitors reduce office SBP by 3-5 mmHg and DBP by 2-3 mmHg across all class members. Corresponding clinically meaningful, significant blood pressure (BP) lowering effects have been confirmed using 24 h ambulatory BP monitoring. SGLT2 inhibitors reduce BP irrespective of the type of background antihypertensive medication. The antihypertensive actions of SGLT2 inhibitors involve several mechanisms including modest diuretic effects, weight loss, and direct vascular effects leading to decreased arterial stiffness and vascular resistance. The first-in class cardiovascular outcome trial with empagliflozin showed a significant reduction in a composite endpoint of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction in T2DM patients at high risk for cardiovascular events. SUMMARY: SGLT2 inhibitors have clinically significant antihypertensive effects. SGLT2 inhibition could be a potentially useful supplement to the BP-lowering treatment armamentarium in patients with T2DM. PMID- 26808706 TI - Human genetics of nephrotic syndrome and the quest for precision medicine. AB - PURPOSE OF REVIEW: In this review, we take a combined membrane biologist's and geneticist's view of the podocyte, to examine how genetics have informed our understanding of membrane receptors, channels, and other signaling molecules affecting podocyte health and disease. RECENT FINDINGS: An integral part of the kidney, the glomerulus, is responsible for the kidney's filter function. Within the glomerulus, the podocyte is a unique cell serving a critically important role: it is exposed to signals from the urinary space in Bowman's capsule, it receives and transmits signals to/from the basement membrane upon which it elaborates, and it receives signals from the vascular space with which it also communicates, thus exposed to toxins, viruses, chemicals, proteins, and cellular components or debris that flow in the blood stream. Our understanding of how podocytes perform their important role has been largely informed by human genetics, and the recent revolution afforded by exome sequencing has brought a tremendous wealth of new genetic data to light. SUMMARY: Genetically defined, rare/orphan podocytopathies, as reviewed here, are critically important to study as they may reveal the next generation targets for precision medicine in nephrology. PMID- 26808707 TI - Wnt/beta-catenin signaling and renin-angiotensin system in chronic kidney disease. AB - PURPOSE OF REVIEW: Intrarenal activation of the renin-angiotensin system (RAS) plays an essential role in the pathogenesis of hypertension and chronic kidney diseases (CKD). However, how RAS genes are regulated in vivo was poorly understood until recently. This review focuses on recent findings of the transcriptional regulation of RAS components, as well as their implication in developing novel strategies to treat the patients with CKD. RECENT FINDINGS: Bioinformatics analyses have uncovered the presence of putative binding sites for T-cell factor/beta-catenin in the promoter region of all RAS genes. Both in-vitro and in-vivo studies confirm that Wnt/beta-catenin is the master upstream regulator that controls the expression of all RAS components tested, such as angiotensinogen, renin, angiotensin converting enzyme and the angiotensin II type I receptor in the kidney. Targeted inhibition of Wnt/beta-catenin, by either small molecule ICG-001 or endogenous Wnt antagonist Klotho, represses RAS activation and ameliorates proteinuria and kidney injury. Blockade of Wnt/beta catenin signaling also normalizes blood pressure in a mouse model of CKD. SUMMARY: These recent studies identify Wnt/beta-catenin as the master regulator that controls multiple RAS genes, and suggest that targeting this upstream signaling could be an effective strategy for the treatment of patients with hypertension and CKD. PMID- 26808708 TI - Targeted inhibition of WRN helicase by external guide sequence and RNase P RNA. AB - Human WRN, a RecQ helicase encoded by the Werner syndrome gene, is implicated in genome maintenance, including replication, recombination, excision repair and DNA damage response. These genetic processes and expression of WRN are concomitantly upregulated in many types of cancers. Therefore, targeted destruction of this helicase could be useful for elimination of cancer cells. Here, we provide a proof of concept for applying the external guide sequence (EGS) approach in directing an RNase P RNA to efficiently cleave the WRN mRNA in cultured human cell lines, thus abolishing translation and activity of this distinctive 3'-5' DNA helicase-nuclease. Remarkably, EGS-directed knockdown of WRN leads to severe inhibition of cell viability. Hence, further assessment of this targeting system could be beneficial for selective cancer therapies, particularly in the light of the recent improvements introduced into EGSs. PMID- 26808709 TI - Acceleration of tumor growth due to dysfunction in M1 macrophages and enhanced angiogenesis in an animal model of autoimmune disease. AB - Both autoimmunity and tumor immunity are immune responses against self-tissues or cells. However, the precise similarity or difference between them remains unclear. In this study, to understand a novel mechanism of tumor immunity, we performed transplantation experiments with a murine autoimmune model, C57BL/6J (B6)/lpr mice. A melanoma cell line, B16F10 cells, or granulocyte macrophage colony-stimulating factor- overexpressing B16F10 (B16F10/mGM) cells were transplanted into B6 or B6/lpr mice. Tumor growth by transplanted B16F10/mGM cells was significantly accelerated in B6/lpr mice compared with that in B6 mice. The accumulation of M1 macrophages in the tumor tissues of B6/lpr recipient mice was significantly lower compared with that in the control mice. In vitro co culture experiment showed that impaired differentiation into M1 macrophages was observed in B6/lpr mice. The number of tumor vessels and vascular endothelial growth factor (VEGF) expression were also significantly enhanced in the tumor tissues of B6/lpr mice compared with those in the B6 mice. Moreover, VEGF expression was correlated with the increased expression of hypoxia-inducible factor-1alpha in the tumor tissues of B6/lpr mice. These results suggest that dysfunctional tumor immunity and enhanced angiogenesis in autoimmunity influence tumor growth. PMID- 26808710 TI - Arterialization and anomalous vein wall remodeling in varicose veins is associated with upregulated FoxC2-Dll4 pathway. AB - Varicose veins of lower extremities are a heritable common disorder. Mechanisms underlying its pathogenesis are still vague. Structural failures such as valve weakness and wall dilatation in saphenous vein result in venous retrograde flow in lower extremities of body. Reflux of blood leads to distal high venous pressure resulting in distended veins. In an earlier study, we observed a positive association between c.-512C>T FoxC2 gene polymorphism and upregulated FoxC2 expression in varicose vein specimens. FoxC2 overexpression in vitro in venous endothelial cells resulted in the elevated mRNA expression of arterial endothelial markers such as Delta-like ligand 4 (Dll4) and Hairy/enhancer-of split related with YRPW motif protein 2 (Hey2). We hypothesized that an altered FoxC2-Dll4 signaling underlies saphenous vein wall remodeling in patients with varicose veins. Saphenous veins specimens were collected from 22 patients with varicose veins and 20 control subjects who underwent coronary artery bypass grafting. Tissues were processed for paraffin embedding and sections were immunostained for Dll4, Hey2, EphrinB2, alpha-SMA, Vimentin, and CD31 antigens and examined under microscope. These observations were confirmed by quantitative real-time PCR and western blot analysis. An examination of varicose vein tissue specimens by immunohistochemistry indicated an elevated expression of Notch pathway components, such as Dll4, Hey2, and EphrinB2, and smooth muscle markers, which was further confirmed by gene and protein expression analyses. We conclude that the molecular alterations in Dll4-Hey2 signaling are associated with smooth muscle cell hypertrophy and hyperplasia in varicose veins. Our observations substantiate a significant role for altered FoxC2-Dll4 signaling in structural alterations of saphenous veins in patients with varicose veins. PMID- 26808711 TI - Long-Term Mortality and Major Adverse Cardiovascular Events in Sepsis Survivors. A Nationwide Population-based Study. AB - RATIONALE: Patients with sepsis who survive to hospital discharge may present with ongoing high morbidity and mortality. However, little is known about the risk of long-term, all-cause mortality and cardiovascular outcomes after sepsis. OBJECTIVES: Our study aimed to investigate the long-term clinical outcomes in sepsis survivors. METHODS: In this nationwide population-based study, data from patients with sepsis were retrieved from Taiwan's National Health Insurance Research Database between 2000 and 2002. Each sepsis survivor was 1:1 propensity matched to control subjects from two different control populations: subjects who were in the general population and subjects who were hospitalized for a nonsepsis diagnosis. The primary outcomes were all-cause mortality, major adverse cardiovascular events, myocardial infarction, heart failure, stroke, and sudden cardiac death or ventricular arrhythmia. MEASUREMENTS AND MAIN RESULTS: Compared with matched population control subjects, sepsis survivors had higher risks of all-cause mortality (hazard ratio [HR], 2.18; 95% confidence interval [CI], 2.14 2.22), major adverse cardiovascular events (HR, 1.37; 95% CI, 1.34-1.41), ischemic stroke (HR, 1.27; 95% CI, 1.23-1.32), hemorrhagic stroke (HR, 1.36; 95% CI, 1.26-1.46), myocardial infarction (HR, 1.22; 95% CI, 1.14-1.30), heart failure (HR, 1.48; 95% CI, 1.43-1.53), and sudden cardiac death or ventricular arrhythmia (HR, 1.65; 95% CI, 1.57-1.74). Similar results, although slightly attenuated risks, were found when comparisons were made with hospitalized control subjects without sepsis. CONCLUSIONS: These data indicate that sepsis survivors had substantially increased risks of subsequent all-cause mortality and major adverse cardiovascular events at 1 year after discharge, which persisted for up to 5 years after discharge. PMID- 26808712 TI - Endothelial Dysfunction in Resistance Arteries of Hypertensive Humans: Old and New Conspirators. AB - A large body of homogeneous reports documented that endothelial dysfunction, which characterizes human essential hypertension is largely dependent on an impaired endothelial nitric oxide availability and an increased production of endothelium-derived contracting factors. These factors include endothelin, prostanoids, and reactive oxygen species (ROS). In particular, it was evidenced that acute intraarterial administration of indomethacin, a nonselective cyclooxygenase (COX)-inhibitor, and ascorbic acid, an antioxidant, normalized the blunted endothelial dysfunction by restoring nitric oxide availability at the level of peripheral microcirculation, thus demonstrating that COX-derived endothelium-derived contracting factors are one of the major sources of ROS. Recent studies put in evidence new lights on the mechanisms involved in endothelial dysfunction in human hypertension, identified as "new conspirators." In particular, functional and immunohistochemical experiments with selective COX inhibitors identified the isoform COX-2 as the main source of intravascular ROS generation in isolated small vessels from essential hypertensive patients. In addition, important vascular protective properties by human ghrelin have been demonstrated in human hypertension, in terms that its systemic reduction is involved in the pathophysiology of endothelial dysfunction, while a normalization of its levels may restore vascular homeostasis. PMID- 26808713 TI - Triiodo-L-Thyronine Promotes the Maturation of Cardiomyocytes Derived From Rat Bone Marrow Mesenchymal Stem Cells. AB - Bone marrow mesenchymal stem cells (BMMSCs) can differentiate into cardiomyocytes and be used in cardiac tissue engineering for heart regeneration. However, the effective clinical application of cardiomyocytes derived from BMMSCs is limited because of their immature phenotype. The aim of this study was to investigate the potential of triiodo-L-thyronine (T3) to drive cardiomyocytes derived from BMMSCs to a more mature state. BMMSCs were divided into 3 groups: untreated controls, differentiated, and T3 treated. The differentiation potential was evaluated by immunofluorescence microscopy and flow cytometry. Data were represented as the numbers of cells positive for the troponin I (cTnI), alpha-actinin, GATA4, and the connexin-43 (Cx-43). The mRNA levels of these specific markers of cardiomyocytes were determined by quantitative real-time polymerase chain reaction. The levels of cardiomyocytes markers protein and octamer-binding transcription factor 4 (Oct-4) were determined by Western blot analyses. Our data demonstrate that T3 treatment leads to a significant increase in cells positive for cTnI, GATA4, Cx-43, and alpha-actinin. The mRNA and protein expression levels of these specific markers of cardiomyocytes were also increased after T3 treatment. At the same time, the protein expression level of Oct-4 was substantially downregulated in T3-treated cells. These results demonstrate that T3 treatment increases the differentiation of BMMSCs induced to cardiomyocytes and promotes their maturation. PMID- 26808714 TI - Mechanisms of mesenchymal stem cell correction of the impaired biomechanical properties of diabetic skin: The role of miR-29a. AB - Diabetic skin has impaired wound healing properties following injury. We have further shown that diabetic skin has weakened biomechanical properties at baseline. We hypothesize that the biomechanical properties of diabetic skin decline during the progression of the diabetic phenotype, and that this decline is due to the dysregulation of miR-29a, resulting in decreased collagen content. We further hypothesize that treatment with mesenchymal stem cells (MSCs) may improve diabetic wound healing by correction of the dysregulated miR-29a expression. We analyzed the biomechanical properties, collagen gene expression, collagen protein production, and miR-29a levels in skin harvested from 6 to 18 week old mice during the development of the diabetic phenotype. We also examined the correction of these impairments by both MSC treatment and the inhibition of miR-29a. Diabetic skin demonstrated a progressive impairment of biomechanical properties, decreased collagen content, and increased miR-29a levels during the development of the diabetic phenotype. MSC treatment decreased miR-29a levels, increased collagen content, and corrected the impaired biomechanical properties of diabetic skin. Additionally, direct inhibition of miR-29a also increased collagen content in diabetic skin. This decline in the biomechanical properties of diabetic skin during the progression of diabetes may increase the susceptibility of diabetic skin to injury and miR-29a appears to play a key role in this process. PMID- 26808715 TI - A causal relationship between hearing loss and cognitive impairment. AB - CONCLUSION: Moderate hearing loss in young mice caused decreases in cognition associated with spatial working and recognition memories in 6 months. These results provide evidence for a causal relationship between hearing loss and cognitive impairment. OBJECTIVES: Hypothesized mechanisms to connect sensory and cognitive functions include the sensory-deprivation, information-degradation, and common-cause hypotheses. This study intended to investigate the effect of hearing loss on cognitive function, as estimated by radial arm maze (RAM) and novel object recognition (NOR) tasks in mice through age- and hearing-matched longitudinal work during a 6-month period. METHODS: Twenty-four male C57BL/6 mice aged 1 month with normal ABR thresholds were used. Twelve mice in the hearing loss (HL) group were exposed to white noise at 110 dB SPL for 60 min every day for 20 days. At post-noise 6 months, all mice underwent RAM and one-trial NOR test. RAM performance measures and NOR discrimination index were compared between two groups. RESULTS: At 6 months after noise exposure, all mice in the experimental group had moderate hearing loss. Most of the RAM performances improved gradually within each group across five trials, probably due to learning effect. The HL group showed lower performance scores than the control group in several trial points in the RAM task. The contact time with the novel object was shorter in the HL group than in the control group. PMID- 26808716 TI - Reaching vulnerable groups. PMID- 26808717 TI - Benchmarking DFT and semi-empirical methods for a reliable and cost-efficient computational screening of benzofulvene derivatives as donor materials for small molecule organic solar cells. AB - A systematic computational investigation on the optical properties of a group of novel benzofulvene derivatives (Martinelli 2014 Org. Lett. 16 3424-7), proposed as possible donor materials in small molecule organic photovoltaic (smOPV) devices, is presented. A benchmark evaluation against experimental results on the accuracy of different exchange and correlation functionals and semi-empirical methods in predicting both reliable ground state equilibrium geometries and electronic absorption spectra is carried out. The benchmark of the geometry optimization level indicated that the best agreement with x-ray data is achieved by using the B3LYP functional. Concerning the optical gap prediction, we found that, among the employed functionals, MPW1K provides the most accurate excitation energies over the entire set of benzofulvenes. Similarly reliable results were also obtained for range-separated hybrid functionals (CAM-B3LYP and wB97XD) and for global hybrid methods incorporating a large amount of non-local exchange (M06 2X and M06-HF). Density functional theory (DFT) hybrids with a moderate (about 20 30%) extent of Hartree-Fock exchange (HFexc) (PBE0, B3LYP and M06) were also found to deliver HOMO-LUMO energy gaps which compare well with the experimental absorption maxima, thus representing a valuable alternative for a prompt and predictive estimation of the optical gap. The possibility of using completely semi-empirical approaches (AM1/ZINDO) is also discussed. PMID- 26808718 TI - Ocean Wave Simulation Based on Wind Field. AB - Ocean wave simulation has a wide range of applications in movies, video games and training systems. Wind force is the main energy resource for generating ocean waves, which are the result of the interaction between wind and the ocean surface. While numerous methods to handle simulating oceans and other fluid phenomena have undergone rapid development during the past years in the field of computer graphic, few of them consider to construct ocean surface height field from the perspective of wind force driving ocean waves. We introduce wind force to the construction of the ocean surface height field through applying wind field data and wind-driven wave particles. Continual and realistic ocean waves result from the overlap of wind-driven wave particles, and a strategy was proposed to control these discrete wave particles and simulate an endless ocean surface. The results showed that the new method is capable of obtaining a realistic ocean scene under the influence of wind fields at real time rates. PMID- 26808719 TI - Development of Covalent Ligand-Receptor Pairs to Study the Binding Properties of Nonpeptidic Neurotensin Receptor 1 Antagonists. AB - The neurotensin receptor NTS1 has been suggested to be of pharmaceutical relevance, as it was found to exert modulatory effects on dopaminergic signal transduction and to be involved in tumor progression. Rational drug design of NTS1 receptor ligands requires molecular insights into the binding behavior of a particular lead compound. Although crystal structures of NTS1 have revealed the molecular determinants of peptide-agonist interactions, the binding mode of small molecule antagonists remains largely unknown. Employing a disulfide-based tethering approach, we developed covalently binding molecular probes. The ligands 1 and 2 are based on the pharmacophore of the nonpeptidic NTS1 antagonist SR142948A, allowing the formation of a disulfide bond to an engineered cysteine residue of NTS1. The position of the covalent bond between Cys127(2.65) and the ligand was used to predict the binding mode of the covalent antagonist 1 and its parent compound SR142948A by molecular dynamics simulations. PMID- 26808720 TI - Biological activity of terpene compounds produced by biotechnological methods. AB - CONTEXT: Biotransformation systems are profitable tools for structural modification of bioactive natural compounds into valuable biologically active terpenoids. OBJECTIVE: This study determines the biological effect of (R)-(+) limonene and (-)-alpha-pinene, and their oxygenated derivatives, (a) perillyl alcohol and (S)-(+)- and (R)-(-)-carvone enantiomers and (b) linalool, trans verbenol and verbenone, respectively, on human colon tumour cells and normal colonic epithelium. MATERIALS AND METHODS: Biotransformation procedures and in vitro cell culture tests were used in this work. Cells were incubated for 24 h with terpenes at concentrations of 5-500 MUg/mL for NR, MTT, DPPH, and NO assays. IL-6 was determined by ELISA with/without 2 h pre-activation with 10 MUg/mL LPS. RESULTS: trans-Verbenol and perillyl alcohol, obtained via biotransformation, produced in vitro effect against tumour cells at lower concentrations (IC50 value = 77.8 and 98.8 MUg/mL, respectively) than their monoterpene precursors, (R)-(+) limonene (IC50 value = 171.4 MUg/mL) and (-)-alpha-pinene (IC50 value = 206.3 MUg/mL). They also showed lower cytotoxicity against normal cells (IC50 > 500 and > 200 MUg/mL, respectively). (S)-(+)-Carvone was 59.4% and 27.1% more toxic to tumour and normal cells, respectively, than the (R)-(-)-enantiomer. (R)-(+) limonene derivatives decreased IL-6 production from normal cells in media with or without LPS (30.2% and 13.9%, respectively), while (-)-alpha-pinene derivatives induced IL-6 (verbenone had the strongest effect, 60.2% and 29.1% above control, respectively). None of the terpenes had antioxidative activity below 500 MUg/mL. DISCUSSION AND CONCLUSIONS: Bioactivity against tumour cells decreased in the following order: alcohols > ketones > hydrocarbons. (R)-(+)-limonene, (-)-alpha pinene, and their derivatives expressed diverse activity towards normal and tumour cells with noticeable enantiomeric differences. PMID- 26808721 TI - Effects of tear gases on the eye. AB - Chemical agents that target the eyes have been a popular choice for law enforcement during riots and for military training for nearly a century. The most commonly used agents are chloroacetophenone (formerly sold as Mace), o chlorobenzylidene malononitrile, and oleoresin capsicum (OC or pepper spray, current ingredient for Mace). Initially, most severe ocular injuries were caused by the explosive force rather than the chemical itself. The development of sprays reduced the mechanical severity of ocular injuries, but resulted in a variety of chemical injuries. The effects on eyes include conjunctival injection, complete corneal epithelial defects, pseudopterygium, corneal neovascularization, persistent conjunctivalization, corneal opacities, and reduced visual acuity. Current management, based on limited human studies, emphasizes decontamination and symptomatic treatment. We review the literature related to clinical and histopathologic effects of tear gas agents on the eye and their management. PMID- 26808722 TI - Rapid Identification of Microorganisms by FilmArray Blood Culture Identification Panel Improves Clinical Management in Children. AB - BACKGROUND: Blood cultures are a common investigation for children admitted to hospital. In routine practice, it takes at least 24 hours to identify an organism as a contaminant or clinically significant. FilmArray Blood Culture Identification Panel (FA-BCIP) is a multiplex polymerase chain reaction that can detect 24 pathogens within 1 hour. We assessed whether results from FA-BCIP lead to changes in clinical management in a tertiary referral paediatric hospital. METHODS: We prospectively studied children having blood cultures taken at our tertiary children's hospital. Blood cultures were monitored and organisms identified using standard methods. FA-BCIP was performed when growth was initially detected in first positive blood cultures per episode, between January 1 and June 30, 2014. Assessment of whether the FA-BCIP result altered clinical management was made, specifically focused on antimicrobial stewardship and length of stay. RESULTS: FA-BCIP was done on 117 positive blood cultures; 74 (63%) grew clinically significant organisms, 43 (37%) grew contaminants. FA-BCIP results were judged to alter clinical management in 63 of the 117 episodes (54%). Antimicrobials were started/altered in 23 (19%) episodes and de escalated/withheld/stopped in 29 (25%) episodes. Ten children were discharged from hospital earlier, which saved a cumulative total of 14 bed days. CONCLUSIONS: Rapid identification of microorganisms in pediatric blood cultures by FA-BCIP, led to changes in clinical management for half of the episodes. This improved antimicrobial stewardship and allowed early discharge from hospital for 10% of children. Future studies should focus on how best to use this technology in a cost-effective manner. PMID- 26808723 TI - Cocolonization of Pneumococcal Serotypes in Healthy Children Attending Day Care Centers: Molecular Versus Conventional Methods. AB - OBJECTIVES: Pneumococci are common colonizer, especially of children, and cocolonization of different serotypes is an important factor for intraspecies genetic exchange. The aim of this study was to analyze pneumococcal carriage and serotype distribution in unvaccinated healthy children in Iceland and compare conventional culture methods and molecular methods using DNA extracted directly from the samples. METHODS: Nasopharyngeal swabs were obtained from 514 children aged 2-6 year attending day care centers in Reykjavik in 2009. The swabs were selectively cultured for pneumococci and the isolates serotyped using latex agglutination. DNA was also extracted directly from the swabs and serotyped using a multiplex PCR panel designed to detect vaccine serotypes and the most commonly carried non-vaccine serotypes. RESULT: Pneumococcal carriage was detected in 391 (76.1%) of the children using polymerase chain reaction (PCR) and in 371 (72.2%) using conventional methods. Cocolonization was detected in 92 (23.5%) of the carriers when PCR method was used and in 30 (8.1%) when conventional methods were used, detecting 500 and 401 strains, respectively (P < 0.0001). The most common serotypes were 23F, 19A, 6B, 6A and 19F, rates 13-8%. The number of isolates of serotypes included in the 10-valent and 13-valent vaccines and detected by PCR were 234 (58.4%) and 363 (90.5%), respectively and by conventional methods 186 (46.4%) and 293 (73.1%), respectively. CONCLUSION: Cocolonization was detected in a fourth of the children carrying pneumococci using DNA extracted directly from nasopharyngeal swabs. The rate of carriage was very high, but no serotype dominated, and the children were commonly colonized by vaccine serotypes, especially cocolonized children. PMID- 26808724 TI - Molecular Epidemiology of Ampicillin-resistant Haemophilus influenzae Causing Acute Otitis Media in Japanese Infants and Young Children. AB - BACKGROUND: Nontypeable Haemophilus influenzae is a particularly important cause of acute otitis media (AOM). There is a high prevalence of beta-lactamase nonproducing ampicillin-resistant (BLNAR) strains in Japanese children, which is associated with recurrent AOM and prolonged treatment. The aim of this study was to investigate the antimicrobial susceptibility profile, mechanisms of ampicillin resistance and molecular epidemiology of ampicillin resistance in H. influenzae strains causing AOM in Japanese children. METHODS: One hundred fifty-seven strains of H. influenzae isolated from the middle ear fluid of pediatric patients (aged 0-3 years) with AOM from various areas of Japan were studied. The antimicrobial susceptibility profile, genes encoding beta-lactamase and alterations of penicillin-binding protein 3 were investigated. Genetic relatedness among ampicillin-resistant isolates was examined by multilocus sequence typing and pulsed-field gel electrophoresis. RESULTS: Of 157 isolates, 108 (68.8%) demonstrated reduced susceptibility to ampicillin, including 95 (60.5%) of beta-lactamase-nonproducing isolates and 13 (8.3%) of beta-lactamase producing isolates. All BLNAR (minimum inhibitory concentration of ampicillin >= 4 mg/L) isolates had amino acid substitutions related to ampicillin resistance. Multilocus sequence typing and pulsed-field gel electrophoresis demonstrated genetic diversity although there were 2 clusters of highly resistant isolates with identical STs (sequence types; ST161 and 549). CONCLUSIONS: Alterations of penicillin-binding protein 3 represented the most prevalent mechanism of ampicillin resistance among H. influenzae isolates causing AOM in Japanese children. BLNAR isolates from children with AOM demonstrated genetic diversity. This study identified for the first time ST clones associated with BLNAR H. influenzae causing AOM in Japanese children. PMID- 26808725 TI - c-myc Gene Copy Number Variation in Cervical Exfoliated Cells Detected on Fluorescence in situ Hybridization for Cervical Cancer Screening. AB - PURPOSE: This study assessed the clinical significance of c-myc gene copy number gain detected by fluorescence in situ hybridization (FISH) in the prediction of cervical intraepithelial neoplasia (CIN) progression. METHODS: We retrospectively investigated 140 Thinprep cytologic test (TCT) specimens that were histopathologically diagnosed with various stages of cervical neoplasia or malignancy. The specimens were subjected to TCT, human papillomavirus (HPV) testing, and FISH analysis with a c-myc-specific probe. The diagnostic reliability of these methods in determining progression was assessed according to sensitivity, specificity, and kappa coefficients. RESULTS: The gene copy number gain of c-myc was significantly higher in the cervical lesion of advanced histologic grade (p < 0.001). For CIN2+ lesions, the sensitivities of TCT, HPV DNA testing, and FISH analysis were 72.3, 92.1, and 64.5%, respectively; the specificities were 81.3, 57.8, and 93.8%, respectively (p < 0.001). The kappa coefficients between the c-myc gene test and either the TCT or the HPV DNA test were 0.538 and 0.399, respectively (p < 0.001). CONCLUSIONS: FISH analysis of the c-myc oncogene could be a useful adjunct screening method for the early diagnosis of high-grade cervical lesions. Moreover, c-myc may be a new molecular biomarker for the early diagnosis of cervical lesion progression. PMID- 26808727 TI - Infection of Mosquito Cells (C6/36) by Dengue-2 Virus Interferes with Subsequent Infection by Yellow Fever Virus. AB - Dengue is one of the most important diseases caused by arboviruses in the world. Yellow fever is another arthropod-borne disease of great importance to public health that is endemic to tropical regions of Africa and the Americas. Both yellow fever and dengue viruses are flaviviruses transmitted by Aedes aegypti mosquitoes, and then, it is reasonable to consider that in a given moment, mosquito cells could be coinfected by both viruses. Therefore, we decided to evaluate if sequential infections of dengue and yellow fever viruses (and vice versa) in mosquito cells could affect the virus replication patterns. Using immunofluorescence and real-time PCR-based replication assays in Aedes albopictus C6/36 cells with single or sequential infections with both viruses, we demonstrated the occurrence of viral interference, also called superinfection exclusion, between these two viruses. Our results show that this interference pattern is particularly evident when cells were first infected with dengue virus and subsequently with yellow fever virus (YFV). Reduction in dengue virus replication, although to a lower extent, was also observed when C6/36 cells were initially infected with YFV followed by dengue virus infection. Although the importance that these findings have on nature is unknown, this study provides evidence, at the cellular level, of the occurrence of replication interference between dengue and yellow fever viruses and raises the question if superinfection exclusion could be a possible explanation, at least partially, for the reported lack of urban yellow fever occurrence in regions where a high level of dengue transmission occurs. PMID- 26808728 TI - MicroRNA Expression Signatures During Malignant Progression From Barrett's Esophagus. AB - The rapid increase and poor survival of esophageal adenocarcinoma (EAC) have led to significant efforts to promote early detection. Given that the premalignant lesion of Barrett's esophagus (BE) is the major known risk factor for EAC, multiple investigators have studied biomarker signatures that can predict malignant progression of BE to EAC. MicroRNAs, a novel class of gene regulators, are small non-coding RNAs and have been associated with carcinogenesis. MicroRNAs are ideal biomarkers because of their remarkable stability in fixed tissues, a common method for collection of clinical specimens, and in blood either within exosomes or as microRNA-protein complexes. Multiple studies show potential of microRNAs as tissue and blood biomarkers for diagnosis and prognosis of EAC but the results need confirmation in prospective studies. Although head-to-head comparisons are lacking, microRNA panels require less genes than messenger RNA panels for diagnosis of EAC in BE. MicroRNA diagnostic panels will need to be compared for accuracy against global measures of genome instability that were recently shown to be good predictors of progression but require sophisticated analytic techniques. Early studies on blood microRNA panels are promising but have found microRNA markers to be inconsistent among studies. MicroRNA expression in blood is different between various microRNA sub-compartments such as exosomes and microRNA-protein complexes and could affect blood microRNA measurements. Further standardization is needed to yield consistent results. We have summarized the current understanding of the tissue and blood microRNA signatures that may predict the development and progression of EAC. PMID- 26808729 TI - A case of IgG4-related lung disease complicated by asymptomatic chronic Epstein Barr virus infection. AB - INTRODUCTION: IgG4-related disease is characterized by IgG4-positive plasmacyte infiltration into various organs, but its etiology is not unknown. OBJECTIVES: To elucidate the etiology of IgG4-related disease. METHODS: We experienced an interesting case of IgG4-related lung disease complicated by chronic EB virus infection. RESULTS: A 70-year-old male visited our hospital due to failure of pneumonia treatment. Chest computed tomography (CT) showed consolidation in the right middle field and slight mediastinal lymphadenopathy in the subcarinal region. Lung consolidation improved with antibiotics; subcarinal lymphadenopathy progressed after 4 months. Malignant lymphoma was suspected given elevated sIL2-R levels (1862 U/mL). Patchy ground glass opacities appeared in the bilateral lung field just before surgical biopsy. He was diagnosed with IgG4-related lung disease after inspection of a pathological specimen obtained from the right upper lung and right hilar lymph node. EB virus-infected cells were also detected in the lymph node. Blood examination revealed EB virus viremia, but the patient did not present with symptoms or organ involvement. This led to a diagnosis of asymptomatic chronic EB virus infection. CONCLUSION: Recent studies have suggested an association between EB virus infection and IgG4-related diseases in the pathological exploration of surgically resected lymph nodes. Our case is the first case of IgG4-related lung disease in which EB virus infection was both pathologically and clinically proved. The present case is of particular interest in view of this newly reported association, and may serve as a fundamental report for future studies connecting EB virus infection with IgG4-related diseases. PMID- 26808731 TI - Quantitative Determination of Zygomaticomaxillary Complex Position Based on Computed Tomographic Imaging. AB - BACKGROUND: The zygomaticomaxillary complex (ZMC) is frequently involved in craniofacial fractures. We propose an objective approach for defining the ZMC position on skeletal and soft tissue by using Amira to process 3-dimensional (3D) facial computed tomography (CT) images. AIM AND OBJECTIVES: In this study, we aim to propose 1 anthropometric system, facilitated based on CT images, which can be used in quantitative analysis of ZMC position and examine the symmetry of skeletal and soft tissue of the ZMC with high reliability and validity. METHODS: Twenty Taiwanese trauma patients with pure mandibular fracture but bilateral intact ZMCs were recruited to participate in this study. The head position was adjusted in 3D planes during the examinations. The distances between the zygion and nasion and maxillozygion and nasion were defined as the x plane. The y plane was defined as the distance between the maxillozygion to the vertex and orbitale to the vertex. The distance between the maxillozygion and opisthocranion was defined as the z plane. RESULTS: The results indicated that the intrasubject variability was 0.7 to 1.6 and 0.1 to 1.8 mm in skeletal and soft tissue, respectively. The intersubject variability ranged from 3.1 to 9.2 and 1.8 to 9.3 mm in skeletal and soft tissue, respectively. The proposed anthropometric system demonstrated high validity and reliability in ZMC measurements. No significant difference was observed among bilateral ZMCs, indicating the feasibility of the mirroring technique during surgical processes. CONCLUSIONS: We conclude that the anthropometric system for processing 3D facial CT images facilitated by Amira has potential implication in the assessment and reconstruction of the ZMC in both skeletal and soft tissue. PMID- 26808732 TI - Primary Overcorrection of the Unilateral Cleft Nasal Deformity: Quantifying the Results. AB - BACKGROUND: Because primary nasal correction by the time of lip repair has been incorporated into the treatment approach, many patients have benefitted from this combined procedure. However, primary nasal correction cannot guarantee an excellent result. Although overcorrection has been mentioned as a treatment rationale of the unilateral cleft lip nasal deformity, a detailed approach and quantitative evidence of the rationale are rare. This study evaluates whether overcorrection in the primary repair results in a quantitative improvement in nasal appearance. PATIENTS AND METHODS: In this retrospective study, the inclusion criteria were patients with complete unilateral cleft lip and palate who underwent primary lip and nose repair by the age of 3 to 4 months. Primary nasal overcorrection was achieved by application of muscle to septal base suture, alar cinching suture and Tajima reversed U incision method. Patients were further divided into an overcorrected (n = 19) and nonovercorrected group (n = 19). The following parameters were identified on basilar photos of all patients taken at least 12 months after repair, ratios of cleft to noncleft side in each patient were taken and the mean for each parameter calculated: Ac angle (ACA/ACA'), alar height (AH/AH'), alar width (AW/AW'), nostril height (NH/NH'), nostril width (NW/NW'), and columellar deviation from the midline (CD/NW). The means of the overcorrected and nonovercorrected groups were then compared using the t test. RESULTS: From all investigated measuremens, Alar height (AH/AH': overcorrected, 0.983 to nonovercorrected, 0.941; P = 0.03) and nostril height ratio (NH/NH') (NH/NH': covercorrected, 0.897 to nonovercorrected, 0.680; P = 0.003) showed statistically significant differences favoring the overcorrected group at least 12 months after surgery. CONCLUSIONS: Primary nasal overcorrection including muscle to columella base suture, alar cinch suture, and Tajima method resulted in quantitatively more long-term symmetric alae and nostril height compared to nonovercorrected patients. PMID- 26808733 TI - Surgical Correction of Nonsyndromic Sagittal Craniosynostosis: Concepts and Controversies. AB - Sagittal craniosynostosis remains the most common type of isolated craniosynostosis, accounting for nearly half of all nonsyndromic cases. The clinical diagnosis is typically made on the basis of a scaphocephalic head shape and is confirmed by computed tomography or magnetic resonance imaging. The current review examines the major surgical options for correction of isolated sagittal craniosynostosis, including their complications and short- and long-term outcomes. Reconstructive techniques have benefited from advances in perioperative anesthesia monitoring and improved safety of blood transfusion. Although extensive calvarial remodeling is considered safe and may confer greater long term skull shape correction and decreased neuropsychological sequelae, minimally invasive techniques, such as device-assisted expansion of the cranium continue to increase in popularity. This review underscores the need for additional prospective studies comparing different techniques to determine the optimal reconstructive approach for correction of sagittal craniosynostosis. PMID- 26808730 TI - RUNX1B Expression Is Highly Heterogeneous and Distinguishes Megakaryocytic and Erythroid Lineage Fate in Adult Mouse Hematopoiesis. AB - The Core Binding Factor (CBF) protein RUNX1 is a master regulator of definitive hematopoiesis, crucial for hematopoietic stem cell (HSC) emergence during ontogeny. RUNX1 also plays vital roles in adult mice, in regulating the correct specification of numerous blood lineages. Akin to the other mammalian Runx genes, Runx1 has two promoters P1 (distal) and P2 (proximal) which generate distinct protein isoforms. The activities and specific relevance of these two promoters in adult hematopoiesis remain to be fully elucidated. Utilizing a dual reporter mouse model we demonstrate that the distal P1 promoter is broadly active in adult hematopoietic stem and progenitor cell (HSPC) populations. By contrast the activity of the proximal P2 promoter is more restricted and its upregulation, in both the immature Lineage- Sca1high cKithigh (LSK) and bipotential Pre Megakaryocytic/Erythroid Progenitor (PreMegE) populations, coincides with a loss of erythroid (Ery) specification. Accordingly the PreMegE population can be prospectively separated into "pro-erythroid" and "pro-megakaryocyte" populations based on Runx1 P2 activity. Comparative gene expression analyses between Runx1 P2+ and P2- populations indicated that levels of CD34 expression could substitute for P2 activity to distinguish these two cell populations in wild type (WT) bone marrow (BM). Prospective isolation of these two populations will enable the further investigation of molecular mechanisms involved in megakaryocytic/erythroid (Mk/Ery) cell fate decisions. Having characterized the extensive activity of P1, we utilized a P1-GFP homozygous mouse model to analyze the impact of the complete absence of Runx1 P1 expression in adult mice and observed strong defects in the T cell lineage. Finally, we investigated how the leukemic fusion protein AML1-ETO9a might influence Runx1 promoter usage. Short term AML1-ETO9a induction in BM resulted in preferential P2 upregulation, suggesting its expression may be important to establish a pre-leukemic environment. PMID- 26808734 TI - The Effects of Desferroxamine on Bone and Bone Graft Healing in Critical-Size Bone Defects. AB - BACKGROUND: Autogenous bone grafts are still the criterion standard treatment option in critical-size bone defect reconstructions, and many therapies can affect its incorporation. In this study, it was aimed to research the effects of desferroxamine (DFO) application on bone and bone graft healing due to the effects of osteoblast and osteoclast regulation and stimulation of angiogenesis. METHODS: Rat zygomatic arch critical-size bone defect model (5 mm) was used as the experimental model. Thirty-two Sprague-Dawley rats (64 zygomatic arches) were divided into 4 groups (16 zygomatic arches in each). In groups 1 and 2, defects were reconstructed with the bone grafts harvested from the other side, and the right arc was named as group 1, and the left was group 2. At group 1, 200 MUM/300 MUL dosage of DFO was injected at the zygomatic arch region starting at the seventh day preoperatively and lasting until the 45th day postoperatively. Group 2 animals were defined as the control group of group 1, and 0.9% NaCl injection was applied. In groups 3 and 4, there was no repair after the formation of defects, and the right arc region was treated with DFO, and left was treated with 0.9% NaCl for postoperative 45 days, respectively. Radiological (computed tomography), histological (hematoxylin-eosin), and biomechanical (3-point bending test) tests were used for the evaluation. RESULTS: In radiological evaluation, there was a statistically significant decrease (P < 0.05) in bone defect size in group 3 animals at the 4th, 8th, and 12th weeks, and bone graft volume showed a statistical difference at all weeks (P < 0.05). In histological evaluation, it was observed that there was an increase in osteoblast number and vascularity rates (P < 0.05) in the DFO-treated groups at all weeks. Biomechanical evaluation of the subjects showed increase in bone strength in group 1 animals at 12 weeks. CONCLUSIONS: In this study, it was shown that DFO treatment increased bone graft incorporation and healing in critical-size bone defects. In this aspect, we suggest that DFO can be used to increase graft incorporation in risky areas and reduce the defect size in patients who are not suitable for vascularized bone graft transfer. PMID- 26808735 TI - Is the Target of 1 Day of Stay per 1% Total Body Surface Area Burned Achieved in Chemical Burns? AB - The length of hospital stay (LOS) is a standard parameter used to reflect quality and evaluate outcomes in acute burn care. This study aims to assess whether the target of 1 day of stay per 1% total body surface area (TBSA) burned was achieved in acute chemical burns management and factors affecting the LOS. A retrospective analysis of the records of patients who suffered from chemical burn injuries admitted to a university burn center over a continuous 14-year period was performed.A total of 118 patients were admitted over the period for chemical burns. Only 14% of cases achieved the target stated. Factors associated with lengthening of the hospital stay included TBSA, ocular involvement, the cause of injury, and the need for surgery during the same admission.The LOS in chemical burns frequently exceeds 1 day of stay per 1% TBSA burned. Many factors can contribute to a patient's LOS and are worth exploring in order to see if the impact of these factors could be minimized. Early surgical intervention should help to reduce the LOS if reliable methods of burn wound depth assessment are available. PMID- 26808736 TI - Clinical Manifestation, Diagnosis, and Surgical Treatment of Chronic Radiation Ulcers Related to Percutaneous Coronary Intervention. AB - Chronic radiation ulcers that develop after cardiac catheterization have become common recently because of the rapid increase in the use of diagnostic and interventional cardiac catheterization procedures. However, their diagnosis and treatment remain difficult. We encountered 10 patients with National Cancer Institute grade 4 radiation ulcers related to prolonged percutaneous coronary intervention. Data of these 10 patients, including clinical presentations and treatments, were collected and analyzed. A quality-of-life questionnaire was administered to the patients preoperatively and postoperatively. Most of the lesions (8/10 patients) were located on the back. All of the patients received prolonged cardiac catheterization lasting for more than 3 hours, at least once, and all of the coronary artery lesions showed chronic total or near-total occlusion. The surgical procedures included complete resection of the lesion followed by fasciocutaneous flap coverage (9/10) or skin grafting (1/10). The mean +/- SD follow-up time was 23.3 +/- 19.79 months, and the wounds in all the patients healed well without complications. After the surgery, the symptoms reduced and the quality of life improved significantly according to the scores in the quality-of-life questionnaire. In conclusion, the early diagnosis of chronic ulcers related to prolonged percutaneous coronary intervention depends on careful history taking and a highly suspicious clinical presentation. For National Cancer Institute grade 4 radiation ulcers, complete resection and immediate reconstruction with flaps or grafts may improve the symptoms and achieve reliable wound coverage without complications. PMID- 26808737 TI - Atypical Lipomatous Tumors of the Extremities and Trunk Wall-The First Case Series of Chinese Population With 45 Cases. AB - BACKGROUND: Atypical lipomatous tumor (ALT) is a low-grade, slow-growing, locally aggressive malignant mesenchymal neoplasm. ALT of the extremities and trunk wall is associated with a relatively favorable outcome. However, these tumors can still recur locally and secondary dedifferentiation after recurrence has been reported. There is currently no consensus about the optimal surgical treatment of ALT. Therefore, we aimed to clarify the clinical behavior, appropriate treatment, and outcomes of ALT of the extremities and trunk wall. METHODS: We retrospectively reviewed the files of 45 patients treated between 2000 and 2014 with the diagnosis of atypical lipomatous tumors of the extremities and trunk wall at our institution. The median follow-up period was 84.5 months (range, 24 183 months). The patient demographics, clinical presentation, surgical methods, margin status, and administration of radiation therapy were recorded. Patients were evaluated for their local recurrence, dedifferentiation, and postoperative complications. RESULTS: Wide resection was performed on 11 patients, and marginal resection was performed on 34 patients. Seven patients underwent adjuvant radiotherapy. The overall recurrence rate was 17.8% (8/45), and dedifferentiation rates was 0% (0/8). The mean time to local recurrence was 5.25 years (range, 2.6 10.6 years). No ALT-related deaths occurred during the follow-up period. There were no differences in recurrence-free survival for the different surgical methods (P = 0.337) and radiotherapy (P = 0.228), whereas the R0 resection had better recurrence-free survival (P = 0.031). The postoperative complication rates were higher in wide resection group than in marginal resection group. (45.5% vs 14.7%, P = 0.048). CONCLUSIONS: Atypical lipomatous tumors of the extremities and trunk wall are associated with a favorable overall survival and do not metastasis. Although they have a tendency to recur, the risk of secondary dedifferentiation is small. Wide resection had similar recurrence rates to marginal resection, but it might lead to more complications. Therefore, marginal resection is considered appropriate for the treatment of ALTs. PMID- 26808738 TI - On Beyond Lidocaine: Reconsidering Local Anesthetics in Tumescent Liposuction-A Critical Review. AB - The use of tumescent solution in liposuction is now considered standard of care; however, much debate still exists regarding its ideal components, especially surrounding the inclusion of local anesthetics. This article reviews the discussion regarding the use of local anesthetics in tumescent liposuction and how it may evolve in the future. The need for local anesthetic additives in tumescent liposuction has been questioned, and the use of longer-acting agents discouraged; however, increasing number of reports in recent years have described the increasingly widespread use of tumescent anesthesia where a wetting solution is infiltrated to achieve anesthesia in an operative field for procedures other than liposuction. More high-level evidence, such as randomized controlled clinical trials, will be required; however, it should be possible to develop a useful standardized algorithm that can guide surgeons to optimize patient safety as well as patient experience. PMID- 26808739 TI - Cranioplasty Using a Novel Osteoconductive Scaffold and Platelet Gel. AB - BACKGROUND: Commonly used materials for cranioplasty include autogenous bone grafts, methyl methacrylate, and titanium mesh. We evaluated a novel osteoconductive scaffold [N-isopropylacrylamide cross-linked with acrylic acid using gamma-rays (ANa powder)] mixed with platelet gel for cranioplasty. METHODS: ANa powder mixed with platelet gel was implanted into a 15 * 15-mm, full thickness calvarial bone defect in 5 New Zealand white rabbits. ANa powder mixed with phosphate-buffered saline was implanted in 5 rabbits. The calvarial bone defect was left unreconstructed in another 5 rabbits. Twelve weeks after surgery, computed tomography examination was used to evaluate the radiographic evidence of bone healing in vivo. Bone specimens were then retrieved for histologic study. RESULTS: The ANa scaffold mixed with platelet gel is biocompatible, biodegradable, and both osteoconductive and osteoinductive, leading to progressive growth of new bone into the calvarial bone defect. CONCLUSION: The use of this novel osteoconductive scaffold combined with osteoinductive platelet gel offers a valuable alternative for the reconstruction of calvarial bone defects. PMID- 26808740 TI - Injected Implant of Uncultured Stromal Vascular Fraction Loaded Onto a Collagen Gel: In Vivo Study of Adipogenesis and Long-term Outcomes. AB - BACKGROUND: Stromal vascular fraction (SVF) cells were used to increase the efficacy of a newly formed adipose tissue in a collagen gel in vitro. However, the outcome of the seeded cells in the collagen gel in vivo remains unknown. We traced the SVF cells in the host tissue and evaluated the efficacy of SVF for fat tissue engineering. METHODS: The aggregates implanted in the experimental and control groups were prepared by mixing SVF with the collagen gel and Dulbecco's modified Eagle medium with the collagen gel, respectively. The aggregates were implanted using a subcutaneous injection into the backs of immunodeficient mice. The aggregates were harvested 1, 2, 4, and 6 months after implantation; and 9 mice were euthanized each time. Macroscopic changes in the volume and wet weight of the aggregates were assessed. The formation of adipose tissue was studied using hematoxylin and eosin and Nile red staining. The origin and survival of adipocytes in the aggregates were examined through the immunostaining of leptin antibodies, DNA assay, and tracing of SVF cells by 1,1'-dioctadecyl-3,3,3',3'- tetramethylindocarbocyanine perchlorate labeling. RESULTS: The formation of adipose tissue was observed in all of the aggregates. Implanted human SVF cells remained in the experimental aggregates harvested after 1, 2, and 4 months but not after 6 months. At 6 months, viable adipocytes in both groups were of murine origin. Furthermore, at 6 months, the mean volume of the aggregate (P < 0.001) and the mean percentage of adipocytes (P < 0.001) were significantly higher in the experimental group than in the control group. CONCLUSIONS: Implanted SVF cells could not be traced in the aggregates harvested at 6 months but promoted the recruitment of host adipocytes to generate more adipose tissue in the experimental group than in the control group. PMID- 26808741 TI - Endoscope-Assisted Pectoralis Major-Rectus Abdominis Bipedicle Muscle Flap for the Treatment of Poststernotomy Mediastinitis. AB - INTRODUCTION: Various management strategies have been reported for sternal wound care; however, they exhibit limited effectiveness or are associated with severe complications. Furthermore, it is difficult for the standard pectoralis major (PM) muscle advance flap to reach the lower third of the sternum. This article examines using the PM-rectus abdominis (RA) bipedicle muscle flap to treat lower third deep sternal wound infection. METHODS: The outcomes of patients who received a PM-RA bipedicle muscle flap harvest at our institution between 1996 and 2014 were reviewed. The method involves performing a subfascial and subperiosteal dissection of the PM to elevate the muscle flap. Blunt dissection may be performed carefully under an endoscope. Endoscope visualization enables us to identify the critical structures lateral to the PM muscle. In addition, the connective tissue to the RA muscle was preserved. Continuity was carefully preserved from the pectoral-thoracoepigastric fascia to the anterior rectus sheath. The flap could then be transposed to fill the lower-third sternal tissue defect with ease. RESULTS: A total of 12 patients, with a mean age of 71 years (45-89 years), were treated using an endoscope-assisted PM-RA bipedicle muscle flap harvest. Wound microbiology of the 12 patients revealed that 3 patients had methicillin-resistant Staphylococcus aureus, 4 had S. aureus, 1 had coagulase negative Staphylococcus, 1 had Escherichia coli, 1 had Pseudomonas aeruginosa, 1 had Mycobacterium tuberculosis, and 1 had a mixed growth of organisms. One instance of recurrent sternal infection was identified among the patients. Moreover, 1 patient died from heart failure 5 weeks after surgery, but the coverage of the sternal wound was successful. Accidental injury to the surrounding neurovascular structure of the patients was avoided, and only 10 to 15 minutes was required to divide the PM muscle. CONCLUSIONS: Performing this harvest method under endoscopic assistance has several advantages, such as preventing excess traction of the skin edge to diminish the skin slough. This method could be an effective alternative for harvesting the PM-RA bipedicle muscle flap to reconstruct the lower-third sternal wound. PMID- 26808742 TI - Superior Gluteal Artery Perforator Flap: The Beauty of the Buttock. AB - BACKGROUND: The superior gluteal artery perforator (SGAP) flap is a useful technique for breast reconstruction. This perforator flap allows for the transfer of the patient's own skin and subcutaneous tissue with minimal donor-site morbidity. Despite its usefulness, the SGAP flap is not widely used among reconstructive surgeons. The challenging perforator dissection and need for microsurgery may contribute to the reluctant use of the flap by many reconstructive surgeons. The ability to perform a single-stage breast reconstruction with buttock tissue when abdominal or thigh tissue are unavailable provides a significant service to the patient desiring an autologous breast reconstruction. METHODS: The authors performed a retrospective review and outcomes analysis of a single surgeon's surgical technique and experience. Consecutive patients, who underwent SGAP flaps for breast reconstruction during a 7-year period from 2007 to 2014, were compared to a matched cohort of consecutive patients undergoing deep inferior epigastric perforator (DIEP) flaps and clinical outcomes were analyzed. RESULTS: Thirteen patients underwent SGAP flap breast reconstruction for a total of 16 flaps during the study period compared to 34 consecutive DIEP flaps for breast reconstruction. There was no significant difference in flap or donor-site complications between the 2 groups. There was no statistically significant difference between the average operative time for unilateral breast reconstruction in the SGAP and DIEP flap groups. In 4 patients, a bipedicled SGAP flap was used due to perforator anatomy. All SGAP patients returned to full activity. Average follow-up time was 1 year. CONCLUSIONS: Although utilization of buttock tissue for breast reconstruction can be challenging and requires microsurgical expertise, in the hands of experienced microsurgeons the SGAP flap is a safe and reliable option for autologous breast reconstruction with minimal donor-site morbidity and excellent aesthetic results. PMID- 26808743 TI - Outcomes Following Oncoplastic Reduction Mammoplasty: A Systematic Review. AB - BACKGROUND: Reconstruction of partial mastectomy defects with oncoplastic approaches has become increasingly popular as a strategy for improving aesthetic outcomes and extending the option of breast conservation therapy. However, interpretation of reported oncologic outcomes and postoperative complications has been challenging because of limited data and significant variability in surgical technique and degree of tissue rearrangement. METHODS: Studies describing oncoplastic mammoplasty or partial mastectomy reconstruction were identified from the MEDLINE and Cochrane databases. Only studies reporting the use of oncoplastic reduction mammoplasty techniques with significant breast parenchymal rearrangement were included for analysis. Primary outcomes assessed were postoperative complications and oncologic outcomes, including local recurrence rates and need for re-excision or completion mastectomy. RESULTS: Seventeen articles met the inclusion criteria, representing 1324 oncoplastic cases. Reported follow-up ranged from 20 to 73 months. Of the 12 studies with at least 2 years' mean/median follow-up, the pooled local-regional recurrence rate was 3.1%. Fifteen articles reported re-excision and completion mastectomy rates (3.5% and 3.7%, respectively). Twelve articles reported postoperative complications. Overall, 4.6% of patients had wound dehiscence, 4.3% developed fat necrosis, 2.8% developed an infection, 0.9% had either partial or total nipple necrosis, and 0.6% had seromas. CONCLUSIONS: Partial mastectomy reconstruction with oncoplastic reduction techniques is associated with high rates of successful breast conservation and low rates of required re-excisions, likely due to the ability to take wide tumor margins without compromising aesthetic outcome. Future studies should consistently report complications, recurrences, and patient-reported outcomes to improve our ability to evaluate the use of this technique. PMID- 26808744 TI - Surgical Timing and Fracture Type on the Outcome of Diplopia After Orbital Fracture Repair. AB - BACKGROUND: Orbital fractures and the concomitant soft tissue injuries within the bony orbit result in well-recognized complications such as diplopia and enophthalmos. Guidelines for timing and indications for surgery for achieving an optimal outcome remain elusive. This study examined the effects of timing and fracture type on the outcome of orbital fracture repair. MATERIAL AND METHODS: Data on 255 patients treated for orbital fractures were retrospectively reviewed to determine the effects of the facial bones involved in the fractures, the types of orbital wall fracture, the timing of surgical repair, and diplopia evident before and after corrective surgery on surgical outcomes. RESULTS: The incidence of posttraumatic diplopia increased with the number of orbital wall fractures (P < 0.001). The rate of diplopia resolution after corrective surgery was slow in the first 3 months irrespective of the severity of orbital wall fracture. The diplopia resolution rate for type I orbital wall fractures was significantly higher than that for type II and type III fractures. Patients treated within 2 weeks of sustaining an orbital fracture exhibited a higher diplopia resolution rate than did patients treated 2 to 4 weeks and more than 4 weeks after sustaining the fracture (58% vs 38.1%). CONCLUSIONS: A higher number of orbital wall fractures are associated with a higher incidence of diplopia and a poorer long-term result. The timing of surgical repair influences the diplopia outcome. Performing corrective surgery for orbital fractures with diplopia after 2 weeks tends to result in a slower complete recovery rate. PMID- 26808745 TI - Excision With Interpositional Nerve Grafting: An Alternative Technique for the Treatment of Morton Neuroma. AB - INTRODUCTION: "Morton neuroma" is a common cause of forefoot pain with numbness frequently occurring in the distribution of the third common digital nerve. After the failure of nonoperative measures, decompression with excision of the neuroma is common practice. Residual numbness and recurrent pain has been reported as a consequence of this treatment option. This study describes excision of the neuroma with interpositional nerve grafting as a treatment option for Morton neuroma. This proposed technique has the benefit of reducing pain, reducing recurrent secondary neuromas and restoring postexcision sensory deficits. METHODS: A retrospective chart review of patients who underwent elective primary excision of a Morton neuroma with interpositional nerve grafting was undertaken. Patient demographics, surgical technique, and clinical outcomes, such as pain, neuroma recurrence, 2-point discrimination, numbness, and weight-bearing status at minimum of 1 year postoperation, are reported. RESULTS: Eight patients (9 neuromas) underwent excision of the Morton neuroma with interpositional nerve grafting after failing nonoperative measures. At final follow-up, all patients had improvement of pain and there were no neuroma recurrences. Sensation to the grafted hemi-toe returned in all but 1 case. All patients returned to full weight bearing status. Although no major complications were reported, wound dehiscence secondary to a hematoma occurred in 1 case. CONCLUSIONS: Excision and interpositional nerve grafting is an effective treatment for Morton neuroma as it alleviates pain, numbness and restores sensation with minimal morbidity and complications. PMID- 26808746 TI - Spontaneous Extensor Tendon Rupture in the Rheumatoid Wrist: Risk Factors and Preventive Role of Extended Tenosynovectomy. AB - OBJECTIVE: Spontaneous extensor tendon rupture is often seen in rheumatoid arthritis (RA) patients, but the risk factors are not clearly defined. We therefore collected the data of RA patients with previous extensor tendon rupture and those with tenosynovitis and analyzed the relationship between extended tenosynovectomy and spontaneous extensor tendon rupture. METHODS: We retrospectively reviewed 17 spontaneous extensor tendon rupture episodes in 15 RA patients and 14 tenosynovitis episodes that required tenosynovectomy in 12 RA patients from 1997 to 2013. Correlations between the incidence of tendon rupture, X-ray findings, and clinical findings in the affected wrists before tendon rupture were analyzed statistically using the test for proportion. RESULTS: The following parameters were significantly correlated with spontaneous extensor tendon rupture: disease duration longer than 8 years, persistent tenosynovitis longer than 1 year duration, and Larsen grade greater than 4 (P = 0.02, 0.03, and 0.01, respectively). Dislocation of the distal end of the ulna, carpal collapse, and the scallop sign on X-ray contributed to a higher spontaneous extensor tendon rupture rate among RA patients (P = 0.01, 0.05, and 0.03, respectively). Extended tenosynovectomy was performed on 14 wrists in 12 RA patients with persistent tenosynovitis longer than 6 months, and Larsen grade did not deteriorate in this group compared with those who did not undergo the surgery. No spontaneous extensor tendon rupture occurred following the surgery. CONCLUSIONS: Risk factors of spontaneous extensor tendon rupture included disease duration longer than 8 years, persistent tenosynovitis longer than 1 year, and wrist Larsen grade greater than 4. Dislocation of the distal end of the ulna, carpal collapse, and the scallop sign on X-ray indicated a higher probability of extensor tendon rupture. Rheumatologists should consult with hand surgeons promptly to preserve hand function before tendon rupture. Prophylactic extended tenosynovectomy surgery to prevent more severe damage of extensor tendon should be recommended in patients who had the above risk factors. PMID- 26808747 TI - The Expanding Role of Education and Research in International Healthcare. AB - A recent report of the Lancet Commission on Global Surgery has continued to emphasize the importance of surgery in global health. Plastic surgeons have been involved in humanitarian care of children in developing countries for many years. The ability to repair children with cleft lip and palate in resource-poor settings has made this desirable for many plastic surgeons. A number of philanthropic plastic surgery organizations arose to deal with the problem in a more structured way. Dr. Donald Laub at Stanford established Interplast (now ReSurg) in 1969. Dr. Bill and Kathy Magee established Operation Smile in 1982, and many others have followed. The unifying theme of these organizations has been the desire to provide safe and effective surgical care to children who would otherwise be forced to live out their lives with deformity. Most care has been for children with clefts, but efforts have expanded to include hand surgery and burn reconstruction. The initial effort was provided through surgical missions. A paradigm shift has occurred as sustainability and local capacity have become paramount. Education and training of local colleagues and assistance in surgical safety infrastructure are expanding the reach of plastic surgical care around the globe. The inauguration of in-country permanent surgical centers allows high volume outcomes research, as well as unique educational collaboration between plastic surgeons of both the developed and developing world. PMID- 26808748 TI - Early Reconstruction of Distal Leg and Foot in Acute High-Voltage Electrical Burn: Does Location of Pedicle in the Zone of Injury Affect the Outcome of Distally Based Sural Flap? AB - BACKGROUND: Distally based fasciocutaneous sural flap is popular in the reconstruction of distal leg and foot burns. However, utilization of this technique in high-voltage electrical injury has been challenging. AIMS: The present study aimed to compare the outcome of early aggressive debridement and coverage of contact point of acute high-voltage electrical injury using distally based fasciocutaneous sural flap between high-risk and low-risk patients defined by the anatomic proximity of the flap pedicle to the zone of injury. METHODS: A total of 51 patients with contact point of high-voltage electrical burn (HVEB) in distal leg and foot undergoing distally based fasciocutaneous sural flap were included in this prospective clinical study. In 28 patients, the flap pedicle was not involved in the contact point of high-voltage electrical injury (low risk/control group), whereas in 21 patients, it was located inside the zone of injury (high-risk/case group). Patients were followed up for a median of 21 months (range, 12-44 months). RESULTS: Wound dimensions to be covered were relatively similar between the 2 groups. Complications of flap survival (primary outcome) and other minor early and late complications (secondary outcome) did not significantly differ between the 2 groups (P > 0.05). CONCLUSIONS: Provided that early and completed debridements of contact points of HVEB were achieved, distally based sural flap is feasible and there is reliable coverage in HVEB even in patients with flap pedicle located in vicinity of the zone of injury. PMID- 26808749 TI - Clinical Patterns of Melanoma in Asians: 11-Year Experience in a Tertiary Referral Center. AB - BACKGROUND: Malignant melanoma is a relatively common malignancy in the West, but has a significantly lower incidence in Asians. Stark contrast in clinicopathological characteristics and prognosis has been observed between the 2 populations, yet data are limited. Here, we evaluate 106 Asian patients from a tertiary referral center in Hong Kong during an 11-year period. The purpose of this study was to collectively review all types of melanomas to analyze the clinicopathological characteristics of this poorly understood condition in an Asian population. METHODS: A total of 106 patients diagnosed with malignant melanoma from 2002 to 2012 were retrospectively reviewed. Demographics, clinical presentations, pathological subtypes, treatments, and survival outcomes were evaluated. RESULTS: Cutaneous melanomas dominated with 46 (43.4%) cases, followed by mucosal (39.6%), ocular (9.4%), and melanomas of unknown primary (7.5%); 43.3% patients presented in stage I, 36.7% in stage II, 18.9% in stage III, and 1.1% in stage IV. Acral lentiginous melanoma was the commonest subtype of cutaneous melanomas (60.9%). When types of melanomas were reviewed collectively, the median overall survival, disease-specific survival, and recurrence-free survival were 37, 45, and 48 months, respectively. Cutaneous melanoma had the best median overall survival of 59 months, followed by ocular melanoma (58 months), mucosal melanoma (18 months), and melanoma of unknown primary (2 months). Similar patterns were observed for disease-specific survival and recurrence-free survival. CONCLUSIONS: Melanoma among Asians remains poorly understood. There is a clear distinction in the clinical patterns between Asians and whites and the difference is not solely accounted for by the lower incidence of cutaneous melanoma. Certain subtypes, such as mucosal melanoma and is acral lentiginous melanoma, seemed to have disproportionately high incidences. Further studies are warranted to elucidate these observations. The poor survival outcomes reflected the need for better awareness and understanding of the condition by both the general public and the physicians. PMID- 26808750 TI - Inpatient Management of Pyoderma Gangrenosum: Treatments, Outcomes, and Clinical Implications. PMID- 26808751 TI - Tissue Dynamics: Lessons Learned From Sutural Morphogenesis and Cancer Growth. AB - Why are cranial sutures the way they are? How do cancers grow? Merging physics and mathematics with biology, we develop equations describing these complex adaptive systems, to which all biological entities belong, calling them laws of tissue dynamics:Where t is time, E is energy, M is body mass, X is the biological characteristic of interest, C is a constant, a is an exponent.(1) is based on conservation of matter: for any given tissue, materials in must equal to materials out +/- assimilated or degraded. (2) is based on energy conservation. All living systems require energy, without which life becomes impossible. Equation (2) is a power spectrum. OBJECTIVES: This study aimed to introduce the laws of tissue dynamics and to illustrate them using observations from craniofacial and cancer growth. METHODS: We use cranial sutures as a model system to test Equation (1), we also measure the in vitro growth rate of normal murine liver and spleen cells, comparing them to B16F10 melanoma cells. We show the increase in compound growth rate and energetic requirement of malignant versus normal cells as partial proof of Equation (2). RESULTS: The constant width and wavy form of cranial sutures are the inevitable results of repeated iteration from coupling of growth and stress. The compound growth rate of B10F16 melanoma cells exceeds that of normal cells by 1.0 to 1.5%, whereas their glucose uptake is equal to 3.6 billion glucose molecules/cell per minute. SUMMARY: Living things are complex adaptive systems, thus a different way of thinking and investigating, going beyond the current reductive approach, is required. PMID- 26808752 TI - The Role of Botulinum Toxin A in the Treatment of Raynaud Phenomenon. AB - Raynaud phenomenon (RP) is a transient digital ischemia that occurs after exposure to cold temperature or emotional distress. It presents with a triphasic course: the initial white phase is followed by cyanotic discoloration and, subsequently, erythema. The attacks may be associated with pain, paresthesia, and complicate with nonhealing ulceration often leading to amputation. To date, there are no clear-cut therapeutic guidelines and many medications are used off-label. Encouraging results were reported with the use of botulinum neurotoxin-A (BoNT A). However, there is still ongoing debate regarding indications, contraindications, best injection technique, and mechanism of action. The aim of this study was to address these issues by providing an up-to-date and detailed overview of the use of BoNT-A in RP.A PubMed database search was conducted. The available studies and techniques were evaluated and compared.The search yielded a total of 29 studies. Ten papers, published between 2004 and 2014, were considered relevant. A total of 128 patients underwent BoNT-A injections. Seventy-five percent to 100 % of the patients reported pain reduction after treatment. Healing of ulcers was reported in 75% to 100% of the affected patients. The most common complication was temporary hand weakness, with an average incidence of 14.1%. Injections targeting the neurovascular bundle at or slightly proximal to the A1 pulley were the most commonly performed.Botulinum neurotoxin-A injection proved to be a valid approach in both primary and secondary RP. The available evidence shows the achievement of both symptomatic and functional improvements in this debilitating condition. However, the patient should be adequately informed about the risk of transient hand weakness. PMID- 26808753 TI - Mechanisms of Fat Graft Survival. AB - Although more fat grafting procedures have been performed by plastic surgeons with the primary goal to restore soft tissue loss, the actual mechanism on how fat graft survives remains less completely understood. An established old theory on fat graft survival is still based on the cell survival theory proposed by Peer in the early 1950s. On the basis of his preliminary experimental study, he proposed that the mechanism of fat graft survival is based on established early blood circulation through anastomosis of the fat graft and host blood vessels. Recently, several investigators have demonstrated new concepts of the fat graft survival: One further advanced the old Peer cell survival theory and another based on new discovery and understanding of adipose-derived stem cells. This article serves as a scientific review on how fat graft survives after in vivo transplantation based on a number of well-conducted experimental studies. Both the graft survival and graft replacement theories on how fat graft survives are true based on the previously mentioned well-conducted experimental studies. Each theory may play a role in fat graft survival. It is possible that graft survival may be more dominant in some patients but the graft replacement may be more dominant in other patients. PMID- 26808754 TI - A Brief History of Two Common Surgical Drains. AB - The use of surgical drains is commonplace in all types of surgical procedures, and rarely do we take the time to contemplate or investigate the origins of these critical devices. Every surgeon should be familiar with the Jackson-Pratt drain and Blake drain, 2 of the most frequently used closed suction, negative-pressure drainage devices in surgery. These drains are used throughout the body in a wide variety of surgical procedures. The development and differences between these 2 devices are seldom known by the practicing surgeon. In this article, we delve into the ancient history of drains, the creation and alterations of the closed suction, negative-pressure drain that paved the way for the Jackson-Pratt and Blake drain. Finally, we will discuss the variety of reservoirs that attach to these drains and the origin of the well-known adage of when to pull a drain. PMID- 26808755 TI - Outcomes of Breast Reconstruction After Mastectomy Using Deep Inferior Epigastric Perforator Flap After Massive Weight Loss. AB - BACKGROUND: Because of the correlation between breast cancer and obesity, plastic surgeons may encounter patients requiring reconstructive breast surgery after massive weight loss (MWL). Use of redundant abdominal skin for deep inferior epigastric artery perforator (DIEP) flap in these patients is a novel concept whose value has not been adequately studied. OBJECTIVE: Assess the outcomes of the DIEP technique for breast reconstruction in the massive weight loss population. PATIENTS: From 103 breast reconstruction patients having 150 DIEP flap procedures, 9 DIEP flaps were performed in MWL patients. Propensity score matching was used in a 1:2 ratio. Eighteen nonweight loss (NWL) patients were selected for comparison with 9 DIEP flaps performed in 6 MWL patients. MEASUREMENTS: Patients in 2 groups were matched for age and body mass index (BMI). Massive weight loss patients were compared with NWL patients on the basis of immediate versus delayed reconstruction and history of radiation; DIEP flap characteristics, including coupler size, additional venous anastomosis, need for re-exploration, and flap loss; length of hospital stay; abdominal wound healing complication; and hernia or bulging. RESULTS: There was no difference in the incidence of flap failures, bulging, or hernias requiring surgery in the MWL group. Additionally, there was no statistical difference in flap survival, abdominal complications, hospitalization days, operative time, or operative characteristics between the 2 groups. There was a significant positive correlation between immediate wound healing complications and comorbidities (P = 0.041). However, there was no correlation between wound healing complications and weight loss history. LIMITATIONS: Only 6 MWL patients of a single surgeon were studied. CONCLUSIONS: For breast reconstruction after mastectomy, DIEP flaps can be used in MWL and NWL populations with equal flap success and abdominal donor site results. Therefore, cosmetic surgeons performing contouring procedures should consider sparing redundant abdominal tissues in patients requiring breast reconstruction. PMID- 26808756 TI - The "Rolled-Up Sleeve" Technique for Microvascular Venous Anastomosis in Head and Neck Reconstruction: Animal Study and Clinical Series. AB - BACKGROUND: Venous anastomosis is challenging especially when encountering the thin recipient vein wall in the head and neck region. The authors developed the "rolled-up sleeve" technique to solve this scenario. METHODS: An animal study was performed to access the safety and reliability of the "rolled-up sleeve" technique. This technique was performed in 53 consecutive patients during head and neck reconstruction. RESULTS: In the animal study, all anastomoses were patent. Histological analysis revealed neo-endothelialization over the anastomotic site. This technique was applied to 59 recipient veins: branch of internal jugular vein (27), external jugular vein (17), superficial temporal vein (9), retromandibular vein (4), facial vein (2), and internal mammary vein (2). No venous thrombosis occurred in these clinical series. CONCLUSIONS: The "rolled-up sleeve" technique is a useful procedure that can be performed safely to deal with thin vascular walls for venous anastomoses in head and neck reconstructions. PMID- 26808757 TI - A Mobile Extracorporeal Extremity Salvage System for Replantation and Transplantation. AB - BACKGROUND: Traumatic amputation is the second leading cause of limb loss in the United States. The preferred treatment is salvage and replantation of the amputated limb, whenever possible, and allotransplantation is a novel procedure whereby healthy limbs are procured from deceased organ donors and transplanted into the amputee recipient. A major restriction for both procedures is the irrecoverable muscle damage occurring due to ischemia. We investigated the feasibility of using a novel lightweight, mobile perfusion device specifically designed to perfuse amputated porcine limbs with an acellular perfusion solution to delay ischemic muscle damage prior to transplantation or replantation. METHODS: Bilateral hind limbs of Yorkshire pigs were amputated; one of the limbs was preserved by perfusion in the mobile perfusion device, and the other by storage in ice slurry for 12 hours. RESULTS: Five sets of bilateral limbs were preserved as described previously. A defined pressure of 30 mm Hg was reliably maintained in the arterial system without loss of flow. Comparison of the perfusate composition before and after limb passage revealed significant differences. Muscle biopsies showed a consistent progression of clusters of hypoxic cells in the control limbs with time. Similar changes could not be observed in the perfused tissue. CONCLUSIONS: We have designed and built a small, mobile perfusion device that is operational and that more closely mimics the normal physiological environment when compared with the current standard of preservation in ice slurry. This project may have far-reaching implications for the treatment of limb loss through replantation and transplantation. PMID- 26808758 TI - Glomus Tumor: Twenty-Year Experience and Literature Review. AB - Glomus tumors are rare, usually benign, vascular hamartomas consisting cells resembling the smooth muscle cells of the normal glomus body. They can be solitary or multiple, whereas solitary tumors are majorly located on the digits. Digital glomus tumors most commonly appear in subungual region and show a strong female predominance. There are several classical symptoms, clinical tests, and imaging tools, such as X-ray, magnetic resonance imaging, and ultrasonography, which can provide good accuracy for clinical diagnosis. However, misdiagnosis and delayed diagnosis are still commonly observed because primary physicians are unfamiliar with classical symptoms and clinical tests. Complete surgical excision often can result in complete relief of symptoms. Recurrence is largely caused by incomplete excision, but repeated image study is recommended to rule out new or malignant lesions. This series is a retrospective review of 50 cases with glomus tumors managed at our institute. We aim to review the key aspects of glomus tumor and provide a simple guideline for earlier diagnosis and treatment. PMID- 26808759 TI - The Effects of Perioperative Tamoxifen Therapy on Microvascular Flap Complications in Transverse Rectus Abdominis Myocutaneous/Deep Inferior Epigastric Perforator Flap Breast Reconstruction. AB - BACKGROUND: Tamoxifen is an important adjunct therapy in breast cancer treatment; however, it has been implicated in increasing microvascular flap complications. Current recommendations on stopping tamoxifen are conflicting and do not address tamoxifen therapy that is continued perioperatively. The purpose of this study is to determine whether tamoxifen taken at the time of free transverse rectus abdominis myocutaneous (TRAM) and deep inferior epigastric perforator (DIEP) flap breast reconstruction affects thrombotic complication rates. METHODS: A retrospective review of microvascular breast reconstruction with TRAM/DIEP flaps over the last 20 years was carried out at a single institution. Patients were divided into 2 cohorts: those receiving tamoxifen at the time of reconstruction (tamoxifen cohort) and those not taking tamoxifen (control). Demographic information, procedural characteristics, and rates of microvascular flap complications were compared. RESULTS: Forty-three patients (56 flaps) received tamoxifen at the time of microvascular breast reconstruction, and 185 patients (267 flaps) did not. Patients in the tamoxifen cohort had a lower mean age of 48.9 years (P = 0.013). A greater percentage of patients in the tamoxifen cohort had preoperative radiation (P < 0.0001) and chemotherapy (P = 0.018) and underwent delayed reconstruction (P < 0.0001). There were no significant differences between the 2 cohorts with regard to flap complications including both arterial and venous thrombosis, flap failure, and other local flap complications. CONCLUSIONS: Patients receiving tamoxifen during TRAM/DIEP flap breast reconstruction did not have increased rates of flap thrombosis or failure; therefore, stopping tamoxifen prior to these procedures may not be necessary. PMID- 26808760 TI - Impact of a Newly Implemented Burn Protocol on Surgically Managed Partial Thickness Burns at a Specialized Burns Center in Singapore. AB - OBJECTIVE: This study evaluated the impact of a newly implemented protocol for superficial to mid-dermal partial thickness burns which involves early surgery and rapid coverage with biosynthetic dressing in a specialized national burns center in Singapore. METHODS: Consecutive patients with 5% or greater total body surface area (TBSA) superficial to mid-dermal partial thickness burns injury admitted to the Burns Centre at the Singapore General Hospital between August and December 2014 for surgery within 48 hours of injury were prospectively recruited into the study to form the protocol group. Comparable historical cases from the year 2013 retrieved from the burns center audit database were used to form the historical control group. Demographics (age, sex), type and depth of burns, %TBSA burnt, number of operative sessions, and length of stay were recorded for each patient of both cohorts. RESULTS: Thirty-nine burns patients managed under the new protocol were compared with historical control (n = 39) comparable in age and extensiveness of burns. A significantly shorter length of stay (P < 0.05) per TBSA burns was observed in the new protocol group (0.74 day/%TBSA) versus historical control (1.55 day/%TBSA). Fewer operative sessions were needed under the new protocol for burns 10% or greater TBSA burns (P < 0.05). CONCLUSIONS: The authors report their promising experience with a newly implemented protocol for surgically managed burns patients which involves early surgery and appropriate use of biosynthetic dressing on superficial to mid-dermal partial thickness burns. Clinically, shorter lengths of stay, fewer operative sessions, and decreased need for skin grafting of burns patient were observed. PMID- 26808761 TI - Medical Student and Primary Care Physician Perception of the Surgical Management of Upper- and Lower-Extremity Peripheral Nerve Entrapment. AB - BACKGROUND: Upper- and lower-extremity peripheral neuropathies are commonly encountered in the primary care setting and account for 14.3 million specialist referrals in the United States annually. Despite the integral role of plastic surgeons in the development of the field of peripheral nerve surgery, plastic surgeons are not commonly recognized as peripheral nerve specialists. The purpose of this study was to investigate the pattern of diagnosis, treatment, and referral of upper- and lower-extremity peripheral nerve entrapment syndromes by both medical students and primary care providers. METHODS: An online survey including 5 peripheral nerve entrapment clinical scenarios (2 upper extremity and 3 lower extremity) was administered to medical students and primary care providers at a large academic medical center. Respondents were surveyed for level of training, prior clinical exposure, initial diagnostic studies of choice, initial therapeutic modalities of choice, need for subspecialty referral, and appropriate surgical subspecialists for management of the peripheral nerve entrapment. RESULTS: Overall, 248 medical students (38.3% response rate) and 54 primary care providers (13.5% response rate) completed the study. The majority of medical students and primary care providers indicated prior clinical experience with upper-extremity peripheral nerve entrapment in contrast to lower-extremity peripheral nerve entrapment with 26.2% and 39.9% of medical students and primary care physicians reporting prior clinical exposure, respectively. Medical students and primary care providers identified orthopedic surgery as the preferred choice for subspecialty referral for both upper- and lower-extremity peripheral nerve entrapment. Primary care physicians are more inclined to initially manage upper extremity nerve entrapment without referral to other specialties than for the management of lower-extremity nerve entrapment; 38.0% and 61.1% of the primary care physicians surveyed would refer to another specialty for the initial management of carpal tunnel and cubital tunnel syndromes, in contrast to 83.0%, 90.0%, and 88.2% for the management of common peroneal nerve compression, sural nerve compression, and deep peroneal nerve compression, respectively. CONCLUSIONS: We contend that early education of medical students and primary care providers regarding the role of plastic surgeons as peripheral nerve specialists may improve future referral patterns. PMID- 26808762 TI - Preoperative Computed Tomography Angiography for Evaluation of Feasibility of Free Flaps in Difficult Reconstruction of Head and Neck. AB - BACKGROUND: Free tissue transfer has been advocated for anatomic and functional reconstruction of soft tissue defects after surgical removal of an extensive recurrent tumor and/or arising from previous irradiation in the head and neck. We report a case series of difficult reconstruction in the head and neck in which preoperative computed tomography (CT) angiography was utilized to evaluate the feasibility of free flap reconstruction. The preoperative radiological evaluation was performed to determine the availability of reliable vessels for anastomosis in free flap reconstruction. If none was found, regional pedicle flap or palliative treatment was applied instead. The use of CT angiography allows the clinical surgeon to perform precise surgical planning with greater confidence. This may improve surgical results, thereby potentially reducing perioperative morbidity. METHODS: Twenty CT angiograms were obtained from 20 patients. All patients were men with a mean age of 57.2 years (range, 42-72 years) and were scheduled to undergo difficult reconstruction in the head and neck. All patients (20/20 [100%]) suffered from oral squamous cell carcinoma. They had all received extensive operations and radiation therapy. Eighteen patients (18/20 [90%]) had completed a course of perioperative irradiation. The CT angiography reports were used to perform detailed preoperative surgical planning accordingly. The findings of CT angiography were classified into 3 groups: group I: normal CT angiography (patent recipient arteries) (Fig. 3); group II: abnormal CT angiography (recipient vessels were present but stenosis or atherosclerotic lesions were noted) (Fig. 4); group III: abnormal CT angiography with no patent recipient arteries in bilateral sides of the neck (Fig. 5); CT angiography results were correlated to the operative findings. RESULTS: The patients were classified into 3 groups based on the angiographic findings. Six patients (6/20 [30%]) were assigned to group I, 8 patients (8/20 [40%]) to group II, and 6 patients (6/20 [30%]) to group III. In groups I and III, all patients (12/12 [100%]) underwent the treatment according to the original preoperative detailed planning. No flap failure was noted in these 2 groups. In group II, 4 patients' recipient vessels (4/8 [50%]) possessed adequate blood flow intraoperatively; hence, microvascular free flaps were transplanted. Venous congestion in 1 case (1/4 [25%]) was noted. The remaining patients in this group (4/8 [50%]) underwent reconstruction with pedicle flaps rather than free flaps because of the lack of suitable target vessels intraoperatively. All flaps (4/4 [100%]) survived. Among the patients who were treated surgically, intraoperative findings were in accordance with those predicted by CT angiography. The total abnormality rate of CT angiography was 70%. Vascular abnormalities detected as a result of preoperative CT angiography led to changes in the operative plan in 50% (10/20) of the patients. CONCLUSIONS: The use of CT angiography should be considered for difficult microsurgical reconstructions in the head and neck. When an abnormality in vascular anatomy is detected by CT angiography, the surgeon is advised to consider altering the operative plan accordingly. This allows precise operation, thereby maximizing the possibility of an optimal outcome. Changing the operative plan based on results of CT angiography may also help to avoid the difficult situation in which the surgeon finds that there are no suitable recipient vessels for free flap reconstruction during the operation. In addition, CT angiography enables surgeons to conduct the preoperative surgical planning with greater confidence, thereby potentially enhancing the success rate of difficult reconstructions in the head and neck, which in turn would tend to improve the perioperative course for the patient and consequently to improve results by decreasing vascular complication rates. PMID- 26808763 TI - The Impact of Hering's Law in Blepharoptosis: Literature Review. AB - The aim of this literature review is to examine Hering's law, a well-documented phenomenon in blepharoptosis patients, with 10% to 20% noted in cases of unilateral ptosis. Predominantly presenting as contralateral eyelid drop postoperatively, it poses a challenge for eyelid surgeons in the pursuit of symmetry and appropriate eyelid height. Proper preoperative evaluation is of utmost importance, consisting of one of either lifting test, covering test, or phenylephrine test. A deeper understanding of Hering's law further provides adequate information for optimal management of ptosis. In regard to ptosis etiology, congenital ptosis does not appear to have a distinct relation to positive Hering's law, commonly associated with a low incidence, when compared with acquired ptosis. Ptosis in the dominant eye seems to be related to a higher incidence of the phenomenon than ptosis in the nondominant eye, with statistical significance in studies ranging from P < 0.001 to P = 0.09. This can be explained as an innate response for increased innervation to regain the field of vision. Both ptosis severity and levator function appear to be of lesser importance than ptosis etiology, with minimal incidence of Hering's law in congenital ptosis regardless of these factors. It is, however, noted that ptosis severity has direct association with contralateral eyelid position in acquired ptosis, whereas there is a lack of studies for levator function. In the event of preoperative contralateral eyelid drop, surgeons should consider simultaneous surgery instead of delayed surgery for bilateral ptosis (P = 0.002). For unilateral ptosis, although reoperation is done per patient request, it may be more appropriate to first wait for roughly 2 weeks and reassess for self-regulation to a normal eyelid position. PMID- 26808764 TI - Risk Factors Analysis for the Outcome of Indirect Traumatic Optic Neuropathy With Steroid Pulse Therapy. AB - BACKGROUND: Although recent evidence suggests a controversy effect of steroids in the management of indirect traumatic optic neuropathy (TON), steroid pulse therapy remains one of the reasonable treatments for patients with indirect TON. It is thought that microcirculatory spasms, edema, and nerve cell necrosis can be prevented or reduced by large doses of steroids. The aim of this study is to analyze the predisposing factors for the recovery of patients with indirect TON who were treated with steroid pulse therapy. MATERIALS AND METHODS: In tracing the 2008 to 2014 data from the Trauma Center of Chang Gung Memorial Hospital, 20 consecutive cases of indirect TON were identified retrospectively. Twenty cases showed no light perception (NLP) under initial ophthalmologic examination. They all received steroid pulse therapy with methylprednisolone in IV form after examination by ophthalmologists, and they did not receive optic nerve decompression. The general data, fracture pattern from images, hospital courses, trauma-related data from ER record, and the initial and final visual data from ophthalmologic records are reviewed. The odds ratio (OR) and 95% confidence intervals (CI) are calculated. Fisher exact test is used for 2 variables to test differences between proportions. Nonparametric statistics are applied to compare the mean values of the data. RESULTS: The results show that for female patients (OR, 3.400; 95% CI, 1.628-7.101; P = 0.049), the administration of methylprednisolone in less than 24 hours from the injury (OR, 3.429; 0.297 39.637), lateral force fracture pattern (OR, 3.500; 0.313-39.153), age of 40 years or younger (OR, 2.333; 0.197-27.567), and pure facial trauma (OR, 3.667; 0.273-49.288) are the predisposing factors for improvement of visual acuity. Patients with orbital blowout fractures (OR, 9.800; 95% CI, 0.899-106.845; P = 0.070), initial free extraocular movement (EOM) (OR, 6.667; 0.809-54.597; P = 0.145), initial intraoptic pressure (IOP) greater than 25 mmHg (OR, 8.000; 0.598 106.936), and higher triage grade (OR, 3.000; 0.447-20.153) are at risk of showing no improvement. CONCLUSIONS: From this study, we might suggest to apply steroid pulse therapy on those patients without contraindication, with an incurring injury less than 24 hours previously. Factors such as sex, age, lateral force fracture pattern, and pure facial trauma revealed a better outcome for improvement of visual acuity. Orbital blowout fractures, initial free EOM, initial IOP greater than 25 mmHg, and higher triage grade suggested poor improvement of visual acuity. PMID- 26808765 TI - Revascularization Surgery: Its Efficacy for Limb Salvage in Diabetic Foot. AB - The estimated prevalence of diabetes is 9.78% in Taiwan. The lifetime risk for patients with diabetes to have foot ulcers might be as high as 25%. About 15% of these patients require major limb amputation because of ischemia and infection. Peripheral artery disease is still a major problem involved in diabetic foot disease and the cause for major amputation despite an increase in the prevalence of revascularization surgery and new revascularization techniques over the past 20 years. We investigated the major limb amputation rates in patients with diabetic foot and critical limb ischemia who had undergone revascularization surgery in our hospital. The records of 42 patients who had undergone revascularization surgery for diabetic foot were retrospectively reviewed. Nineteen patients (45%) required major limb amputation despite revascularization. The affected limbs of only 15 patients (36%) were salvaged. Four patients died soon after surgery because of comorbidities, and another 4 were lost to follow up. Two patients died from procedure-related sepsis, and overall perioperative mortality was 4.8%. Ten predictive risk factors (duration of diabetes, history of smoking, coronary artery disease, congestive heart failure, cerebral vascular accident, contralateral amputation, end-stage renal disease, fever episode, wound infection severity score, and arterial obstruction level) were included for analysis. Although none was significant, long-duration diabetes (OR: 1.13), end stage renal disease (OR: 10.02), wound infection (OR: 1.56), and infrapopliteal lesions (OR: 3.00) tended to be unfavorable predictive risk factors of limb amputation. Revascularization surgery is still potentially beneficial for these patients--eg, it decreases the contralateral limb amputation rate by 7.5%--if done early in high-risk patients. PMID- 26808766 TI - Selective Criteria and Markers in Adipose-Derived Stromal Cells Collection Quality and Expansion Potency. AB - BACKGROUND: Adipose tissue-derived stromal cells (ADSCs) have been extensively used in clinical trials for various therapeutic applications. However, there is a paucity of selective criteria regarding collection and expansion procedures. The purpose of this study was to investigate the effect of liposuction and donor age on ADSCs and to assess the criteria and markers for ADSC long-term expansion potential. METHODS: Adipose tissues were collected using syringe liposuction, water-jet, or ultrasonic techniques. Tissue/cell viability was evaluated using the XTT assay. CD34 and SSEA-4 expression were examined using flow cytometry. SOX2 gene expression was estimated using quantitative polymerase chain reaction, and Nile-red staining was performed to evaluate the adipogenesis potency during ADSC expansion. RESULTS: The lipoaspirates obtained from syringe and ultrasonic liposuction methods were superior to those of the water-jet method in stromal vascular fraction yield and durability during temporary storage. SSEA-4, SOX2 expression, and adipogenesis potency of early-passage ADSCs were significantly correlated with the P15 cumulative population doublings data. CD34 expression was strongly correlated with P0 ADSC yield and doubling time. Tissue viability, P0 ADSC CD34+ percentage, and P15 cumulative population doublings were decreased along with donor age. CONCLUSIONS: This study established criteria and markers to determine whether lipoaspirate tissue and cultured ADSCs are suitable for further large-scale expansion and allogenic universal cell banking. PMID- 26808767 TI - Surgical Correction of the Intractable Blepharoptosis in Patients With Ocular Myasthenia Gravis. AB - PURPOSE: Treatment of blepharoptosis caused by ocular myasthenia gravis (OMG) is challenging in patients with serious side effects or failed response to medical therapy. Only a few surgical reports have been published for refractory myathenic blepharoptosis. This study is aimed at the evaluation of the surgical outcome of blepharoptosis correction in intractable OMG patients. METHODS: Twelve OMG patients who accepted frontalis sling with frontalis orbicularis oculi muscle (FOOM) flap for blepharoptosis correction were reviewed. Patients' demographies, perioperative changes of the interpalpebral fissure height (IPFH), margin reflex distance 1 (MRD1), levator function (LF), and quality of life (QOL) score were evaluated. RESULTS: The duration of OMG ranged from 3 to 31 years. LF was normal in 6 patients, good in 5, and poor in 1. There is no significant change of LF before and after surgery. MRD1 improved significantly from -1.8 mm (range, 0 to 5 mm) preoperatively to 2.9 mm (range, 2-4 mm) postoperatively. IPFH improved significantly from 3.8 mm (range, 2-6 mm) preoperatively to 7.8 mm (range, 6-9 mm) postoperatively. Upper eyelid margin was above the pupil in all patients. QOL score improved significantly from 18.2 (range, 14-23) preoperatively to 5.8 (range, 0-10) postoperatively. CONCLUSIONS: Our report reveals that surgical correction of the blepharoptosis is effective for patients with intractable OMG and that frontalis suspension with FOOM flap is a valuable option because of its ready availability and pliability. All patients are satisfied with the results, especially the improvement of QOL. PMID- 26808768 TI - The Effect of BMI on Outcomes Following Complex Abdominal Wall Reconstructions. AB - BACKGROUND: The management of complex abdominal wall defects continues to be a challenging process secondary to the high potential for wound healing issues and ventral hernia recurrences. Body mass index (BMI) is a well-known risk factor when it comes to complications. We hypothesize that higher BMIs result in higher rates of postoperative complications in complex abdominal wall reconstructions (CAWRs). METHODS: We retrospectively reviewed all patients who underwent CAWR at Emory University Hospital over a 12-year period. Patients were divided into 4 cohorts based on BMI (15-24.9, 25-29.9, 30-34.9, and >=35 kg/m). Complication rates among the 4 groups were evaluated as the primary outcome using Pearson chi analysis. Further analysis was done on specific complications including mesh exposure, skin necrosis, delayed healing, rate of fistula formation, seroma, hematoma, infection, rate of recurrence, and rate of reoperation. RESULTS: We included 313 patients with a mean follow-up of 15.6 months. The rate of overall complications demonstrated a nonsignificant increase with BMI of 15 to 24.9, 25 to 29.9, 30 to 34.9, and 35 kg/m or greater (31.7%, 35.0%, 47.6%, and 48.3%; P = 0.079, respectively). The rate of skin necrosis was significantly increased in the higher BMI groups (1.7%, 1.3%, 9.5%, and 13.5%; P = 0.004). The rate of ventral hernia recurrence was significantly increased in the higher BMI groups (8.3%, 12.5%, 29.8%, and 27.0%; P = 0.002). Rates of reoperation were also statistically increased in the higher BMI groups (25.0%, 22.5%, 41.7%, and 34.8%; P = 0.035). Rates of mesh exposure, delayed healing, fistula formation, seroma, hematoma, and infection were not statistically significant among the 4 BMI groups. CONCLUSIONS: Patients undergoing CAWR with BMIs greater than 30 kg/m have significantly higher rates of skin necrosis, hernia recurrence, and reoperation compared with subgroups of lower BMI. Rates of overall complications among all BMI groups are similar, although trended up with BMI. Surgeons should weight the risks and benefits of CAWR in patients with higher BMIs to reduce specific postoperative complications. PMID- 26808769 TI - Full-Length Finger Reconstruction for Proximal Amputation With Expanded Wraparound Great Toe Flap and Vascularized Second Toe Joint. AB - BACKGROUND: Most of the frequently used methods for finger reconstruction have their own limitations. Reconstruction of a full-length finger with normal appearance, in patients with proximal digital amputation, remains a challenge. METHODS: Between January 2002 and November 2013, a total of 86 fingers (60 patients) with proximal phalanx amputation were surgically repaired. A compound flap comprising an expanded wraparound flap from the great toe and a vascularized proximal interphalangeal (PIP) joint from the second toe was harvested to reconstruct a full-length finger. The flap was used to reconstruct the nail, skin, and the distal phalanx; the PIP joint was used to reconstruct the PIP joint. To attain normal length of the finger and right PIP joint positioning, an iliac bone graft was inserted into the distal-middle or proximal phalanx. RESULTS: All reconstructed fingers retained their viability and natural appearance and were of near-normal length with a normal PIP joint positioning; 12.8% (9/86) of the procedures required re-exploration owing to compromised circulation. Secondary procedures were required in 71% (61/86) of the cases. With the exception of 1 case, the donor-site complications were mild; the average range of motion at the other PIP joints was 52 degrees (-15 to -5 degrees of extension, 25-90 degrees of flexion). Approximately 80% of the normal functionality and 93% of the normal appearance with respect to aesthetics were restored. CONCLUSIONS: The full-length finger reconstruction procedure allows for construction of natural-appearing full-length fingers with normal PIP joint positioning and a near-normal functional recovery for proximal digital amputation. The operation is technically complex and time consuming and demands a skilled operator for successful outcomes. PMID- 26808770 TI - Intracompartmental Sepsis With Burn: A Case Report. AB - Intracompartmental sepsis (IS) is a rare complication in patients with burns. Intracompartmental sepsis presents in patients with inadequate perfusion of intracompartmental tissues and subsequent ischemic necrosis and infection. Contributing factors include high-volume resuscitation, delayed escharotomies, and previous bacteremia. We describe a case of massive burns from a gas explosion and the subsequent development of IS in our intensive care burn unit. The patient presented with a 75% total body surface area burn on admission, with 39% superficial, deep partial-thickness and 26% full-thickness burns. Intracompartmental sepsis was diagnosed 45 days after admission. Anterior compartment muscles, including the tibialis anterior, extensor hallucis longus, and extensor digitorum longus, were necrotic with relatively fair nerve and vascular structures. Intracompartmental sepsis is an overwhelming, infectious complication that appears late and can occur easily in patients with major burns. Early diagnosis and management are a must for improving outcomes. PMID- 26808771 TI - Experience in Reconstruction for Small Digital Defects With Free Flaps. AB - Traumatic injuries to the digits resulting in soft tissue or bone loss require reconstruction. Traditionally, local flaps, such as homodigital flaps, heterodigital flaps, pedicled flaps, or distant flaps, are used for digital resurfacing. However, free tissue transfers can be used in selected patients. In this study, we present the use of different free flaps including groin skin flaps, groin osteocutaneous flaps, groin chimeric flaps, second dorsal metacarpal artery flaps, and partial toe flaps for digital reconstruction. A total of 19 digits were treated with 16 free flaps in our hospital. Of the flaps used, 5 were free groin skin flaps, 4 were free partial toe flaps, 3 were free groin chimeric flaps, 2 were free groin osteocutaneous flaps, and 2 were free second dorsal metacarpal artery flaps. The average flap size was 4.7 * 2.0 cm (range, 1.5 * 1 to 5 * 4 cm), and the average operative time was 6.0 hours (range, 4-9 hours). All flaps survived without partial or total necrosis. In conclusion, the free flap is a reliable and safe alternative for digital reconstruction. Moreover, the free groin flap provides not only a chimeric pattern for multiple fingers coverage but also an osteocutaneous pattern for thumb lengthening. The free second dorsal metacarpal artery flap provides a tenocutaneous pattern for tendon reconstruction and soft tissue coverage simultaneously, and the free partial toe flap is an excellent alternative for pulp reconstruction in terms of aesthetic appearance and functional outcome. PMID- 26808772 TI - The Modified Girdlestone Procedure With Muscle Flap for Management of Pressure Ulcers and Heterotopic Ossification of the Hip Region in Spinal Injury Patients: A 15-Year Review With Long-term Follow-up. AB - BACKGROUND: Pressure ulceration, pyogenic arthritis, and hip heterotopic ossification are complications encountered in spinal cord injury patients. The Girdlestone procedure has been established as an effective treatment modality for hip pathology in this population and is particularly efficacious when a muscle flap is used to fill the femoral resection defect. We previously reported its use as a 3-stage procedure. Through time, experience was gained, and consequently, our technique has evolved to a 1-stage procedure. METHODS: A retrospective analysis of all spinal cord injury patients who had undergone Girdlestone arthroplasty or excision of heterotopic ossification by the pressure ulcer management team at Rancho Los Amigos National Rehabilitation Center between 1991 and 2005 was performed. A description of our management, operative protocol, outcome, and complication is given. RESULTS: Over 15 years (between 1991 and 2005), 295 patients underwent 330 procedures. Hips were operated for infection, heterotopic ossification, pressure ulceration, dislocation, femoral head necrosis, or fracture or a combination of the above. Twenty-five cases (7.6%) required surgical revision for wound breakdown in the immediate postoperative period. Average follow-up was 40.3 months; 43.6% of patients developed recurrence of ulceration requiring surgery. The average time until recurrence was 27.3 months. CONCLUSIONS: The Girdlestone arthroplasty is an effective modality to treat hip infection, ankylosis, heterotopic ossification, dislocation, or other pathology associated with the spinal cord injury patient. Long-term follow-up of a large patient population reveals the efficacy of the procedure in preventing recurrence and improving patient quality of life. PMID- 26808773 TI - Heterotopic Vascularized Joint Transfer in Mutilating Hand Injuries. AB - BACKGROUND: In cases of mutilating hand injuries, the primary goal is recovery of prehensile function. This is particularly true in the case of joints, which are extremely difficult to replace or reconstruct adequately when damaged. Heterotopic vascularized joint transfer is indicated when salvageable joints are available for transfer to a more functionally optimal position on the hand. MATERIALS AND METHODS: Seven cases of mutilating hand injuries treated with heterotopic vascularized joint transfers from 2003 to 2012 were retrospectively identified. All patients sustained severe metacarpophalangeal joint (MPJ) or proximal interphalangeal joint (PIPJ) damage that threatened recovery of optimal hand function. All patients were men, with an average age of 34.7 years. Operative, perioperative, and postoperative details including final active range of motion were collected and analyzed. RESULTS: Seven joints were taken from nonsalvageable amputated digits: 4 from the amputated parts, and 3 from the proximal stumps. Five joints were transferred as free flaps requiring microvascular anastomosis, and 2 were transferred on neurovascular pedicles. One joint was lost due to vasospasm. Average active range of motion was 68.3 degrees for homojoint transfers (MPJ to MPJ, PIPJ to PIPJ), and 35 degrees for heterojoint transfers. All but 1 patient were able to achieve tripod pinch; the remaining patient achieved only side-to-side pinch. CONCLUSIONS: Heterotopic vascularized joint transfer is a useful technique to consider in cases of mutilating hand injuries. Improved recovery of prehensile function can be achieved with thoughtful design and execution, followed by proper patient education and rehabilitation. PMID- 26808774 TI - Influence of a visual-verbal Stroop test on standing and walking performance of older adults. AB - The dual task (DT) paradigm has been used to investigate decrements in balance performance while walking and standing in fall prevention studies with older adults. However, there are inconsistent findings whether balance performance decreases or increases in DT situations. Following different theoretical models (e.g. limited resource hypothesis or cross domain competition model), these inconsistent findings can be explained by task settings and task complexity. We compared DT performance in an executive control task (Stroop test) while standing and walking to analyze which theoretical model would fit our data best. Twenty eight persons (>65 years) were examined under single task (ST) and DT conditions for standing (sway length and sway velocity) and walking (step length, step width (SW), peak forces of the heel, mid- and forefoot). SW increased from ST to DT conditions, and step length decreased significantly. Maximum forces of the forefoot were reduced whereas the maximum forces of the midfoot increased. Additionally, correct answers of the Stroop test decreased from the ST baseline condition to DT walking. No correlations were found between DT costs (performance decrements) of standing and walking. For both conditions (standing and walking), the limited resources hypothesis fits best. Moreover, not all modified gait variables could be defined as negative DT costs. Increased SW and decreased step length might be used to compensate influences on lateral stability while demands on motor-cognitive resources increase. Further, drawing conclusions from a standing task for walking conditions might lead to misinterpretations. PMID- 26808776 TI - Aging-induced changes in brain regional serotonin receptor binding: Effect of Carnosine. AB - Monoamine neurotransmitter, serotonin (5-HT) has its own specific receptors in both pre- and post-synapse. In the present study the role of carnosine on aging induced changes of [(3)H]-5-HT receptor binding in different brain regions in a rat model was studied. The results showed that during aging (18 and 24 months) the [(3)H]-5-HT receptor binding was reduced in hippocampus, hypothalamus and pons-medulla with a decrease in their both Bmax and KD but in cerebral cortex the [(3)H]-5-HT binding was increased with the increase of its only Bmax. The aging induced changes in [(3)H]-5-HT receptor binding with carnosine (2.0 MUg/kg/day, intrathecally, for 21 consecutive days) attenuated in (a) 24-month-aged rats irrespective of the brain regions with the attenuation of its Bmax except hypothalamus where both Bmax and KD were significantly attenuated, (b) hippocampus and hypothalamus of 18-month-aged rats with the attenuation of its Bmax, and restored toward the [(3)H]-5-HT receptor binding that observed in 4 month-young rats. The decrease in pons-medullary [(3)H]-5-HT binding including its Bmax of 18-month-aged rats was promoted with carnosine without any significant change in its cerebral cortex. The [(3)H]-5-HT receptor binding with the same dosages of carnosine in 4-month-young rats (a) increased in the cerebral cortex and hippocampus with the increase in their only Bmax whereas (b) decreased in hypothalamus and pons-medulla with a decrease in their both Bmax and KD. These results suggest that carnosine treatment may (a) play a preventive role in aging induced brain region-specific changes in serotonergic activity (b) not be worthy in 4-month-young rats in relation to the brain regional serotonergic activity. PMID- 26808775 TI - The role of TWEAK/Fn14 signaling in the MPTP-model of Parkinson's disease. AB - The tumor necrosis factor like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor-inducible 14 (Fn14), mediate inflammation and neuronal apoptosis in cerebral edema, ischemic stroke and multiple sclerosis. The downstream effectors and pathways linked to TWEAK-Fn14 signaling are strongly implicated in the pathology of Parkinson's disease (PD), thus indicating a putative role for TWEAK/Fn14 signaling in PD neurodegeneration. Using the 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model, we aimed to determine whether genetic ablation or pharmacologic mitigation of the TWEAK protein and its Fn14 receptor affected substantia nigra and striatum Parkinsonian pathology. Changes in endogenous TWEAK protein expression were also quantified in tissue from both MPTP-treated mice and PD human samples. TWEAK protein expression was transiently increased in the striatal tissue but remained unaltered in substantia nigra tissue of MPTP-treated mice. There was also no change of TWEAK protein levels in the substantia nigra or the striatum of human PD patients as compared to matched control subjects. Mitigating the effects of endogenous TWEAK protein using neutralizing antibody did affect MPTP-mediated neurotoxicity in the substantia nigra using the sub-acute model of MPTP (30mg/kg i.p. over five consecutive days). Neither TWEAK nor Fn14 genetic ablation led to attenuation of MPTP-toxicity in the acute model. These findings suggest that TWEAK signaling might be an aspect of MPTP-mediated neuropathology and be involved in the overall neurodegenerative pathology of PD. PMID- 26808777 TI - Single Cell Analysis of a Bacterial Sender-Receiver System. AB - Monitoring gene expression dynamics on the single cell level provides important information on cellular heterogeneity and stochasticity, and potentially allows for more accurate quantitation of gene expression processes. We here study bacterial senders and receivers genetically engineered with components of the quorum sensing system derived from Aliivibrio fischeri on the single cell level using microfluidics-based bacterial chemostats and fluorescence video microscopy. We track large numbers of bacteria over extended periods of time, which allows us to determine bacterial lineages and filter out subpopulations within a heterogeneous population. We quantitatively determine the dynamic gene expression response of receiver bacteria to varying amounts of the quorum sensing inducer N 3-oxo-C6-homoserine lactone (AHL). From this we construct AHL response curves and characterize gene expression dynamics of whole bacterial populations by investigating the statistical distribution of gene expression activity over time. The bacteria are found to display heterogeneous induction behavior within the population. We therefore also characterize gene expression in a homogeneous bacterial subpopulation by focusing on single cell trajectories derived only from bacteria with similar induction behavior. The response at the single cell level is found to be more cooperative than that obtained for the heterogeneous total population. For the analysis of systems containing both AHL senders and receiver cells, we utilize the receiver cells as 'bacterial sensors' for AHL. Based on a simple gene expression model and the response curves obtained in receiver-only experiments, the effective AHL concentration established by the senders and their 'sending power' is determined. PMID- 26808778 TI - Epidemiology and Microbiologic Characterization of Nosocomial Candidemia from a Brazilian National Surveillance Program. AB - Candidemia is a growing problem in hospitals all over the world. Despite advances in the medical support of critically ill patients, candidiasis leads to prolonged hospitalization, and has a crude mortality rate around 50%. We conducted a multicenter surveillance study in 16 hospitals distributed across five regions of Brazil to assess the incidence, species distribution, antifungal susceptibility, and risk factors for bloodstream infections due to Candida species. From June 2007 to March 2010, we studied a total of 2,563 nosocomial bloodstream infection (nBSI) episodes. Candida spp. was the 7th most prevalent agent. Most of the patients were male, with a median age of 56 years. A total of 64 patients (46.7%) were in the ICU when candidemia occurred. Malignancies were the most common underlying condition (32%). The crude mortality rate of candidemia during the hospital admission was 72.2%. Non-albicans species of Candida accounted for 65.7% of the 137 yeast isolates. C. albicans (34.3%), Candida parapsilosis (24.1%), Candida tropicalis (15.3%) and Candida glabrata (10.2%) were the most prevalent species. Only 47 out of 137 Candida isolates were sent to the reference laboratory for antifungal susceptibility testing. All C. albicans, C. tropicalis and C. parapsilosis isolates were susceptible to the 5 antifungal drugs tested. Among 11 C. glabrata isolates, 36% were resistant to fluconazole, and 64% SDD. All of them were susceptible to anidulafungin and amphotericin B. We observed that C. glabrata is emerging as a major player among non-albicans Candida spp. and fluconazole resistance was primarily confined to C. glabrata and C. krusei strains. Candida resistance to echinocandins and amphotericin B remains rare in Brazil. Mortality rates remain increasingly higher than that observed in the Northern Hemisphere countries, emphasizing the need for improving local practices of clinical management of candidemia, including early diagnosis, source control and precise antifungal therapy. PMID- 26808780 TI - Introduction to special issue: Social attention in mind and brain. PMID- 26808779 TI - Identification of Symptomatic Fetuses Infected with Cytomegalovirus Using Amniotic Fluid Peptide Biomarkers. AB - Cytomegalovirus (CMV) is the most common cause of congenital infection, and is a major cause of sensorineural hearing loss and neurological disabilities. Evaluating the risk for a CMV infected fetus to develop severe clinical symptoms after birth is crucial to provide appropriate guidance to pregnant women who might have to consider termination of pregnancy or experimental prenatal medical therapies. However, establishing the prognosis before birth remains a challenge. This evaluation is currently based upon fetal imaging and fetal biological parameters, but the positive and negative predictive values of these parameters are not optimal, leaving room for the development of new prognostic factors. Here, we compared the amniotic fluid peptidome between asymptomatic fetuses who were born as asymptomatic neonates and symptomatic fetuses who were either terminated in view of severe cerebral lesions or born as severely symptomatic neonates. This comparison allowed us to identify a 34-peptide classifier in a discovery cohort of 13 symptomatic and 13 asymptomatic neonates. This classifier further yielded 89% sensitivity, 75% specificity and an area under the curve of 0.90 to segregate 9 severely symptomatic from 12 asymptomatic neonates in a validation cohort, showing an overall better performance than that of classical fetal laboratory parameters. Pathway analysis of the 34 peptides underlined the role of viral entry in fetuses with severe brain disease as well as the potential importance of both beta-2-microglobulin and adiponectin to protect the injured fetal brain infected with CMV. The results also suggested the mechanistic implication of the T calcium channel alpha-1G (CACNA1G) protein in the development of seizures in severely CMV infected children. These results open a new field for potential therapeutic options. In conclusion, this study demonstrates that amniotic fluid peptidome analysis can effectively predict the severity of congenital CMV infection. This peptidomic classifier may therefore be used in clinical settings during pregnancy to improve prenatal counseling. PMID- 26808781 TI - Effects of a Novel Therapeutic Intervention in Patients With Diabetic Peripheral Neuropathy. AB - OBJECTIVE: To determine the effect of a novel therapeutic intervention called intraneural facilitation on balance measures and a neuropathy scale in patients with diabetic peripheral neuropathy. DESIGN: Prospective pre- and posttest, single group clinical trial. SETTING: Outpatient physical therapy clinic. PARTICIPANTS: Patients with diabetic peripheral neuropathy (N=13). INTERVENTION: Subjects received 10 sessions of intraneural facilitation. MAIN OUTCOME MEASURES: The modified Total Neuropathy Scale, the NeuroCom SMART Balance Master system computerized dynamic posturography (CDP) that includes the Sensory Organization Test (SOT) and the limits of stability (LOS), and the Activities-specific Balance and Confidence (ABC) scale. RESULTS: Subjects in this study showed significant improvement in the modified Total Neuropathy Scale, SOT, and 1 component in the LOS test (movement velocity). There were no significant differences in the ABC scale or in 4 components of the LOS test, which were reaction time, end point excursion, maximum excursion, and directional control. CONCLUSIONS: Intraneural facilitation improved objective balance measures and neuropathy symptoms in patients with diabetic peripheral neuropathy. Further study is needed to determine long-term benefits of this intervention. PMID- 26808782 TI - Randomized Controlled Trial of a Home-Based Action Observation Intervention to Improve Walking in Parkinson Disease. AB - OBJECTIVE: To examine the feasibility and efficacy of a home-based gait observation intervention for improving walking in Parkinson disease (PD). DESIGN: Participants were randomly assigned to an intervention or control condition. A baseline walking assessment, a training period at home, and a posttraining assessment were conducted. SETTING: The laboratory and participants' home and community environments. PARTICIPANTS: Nondemented individuals with PD (N=23) experiencing walking difficulty. INTERVENTION: In the gait observation (intervention) condition, participants viewed videos of healthy and parkinsonian gait. In the landscape observation (control) condition, participants viewed videos of moving water. These tasks were completed daily for 8 days. MAIN OUTCOME MEASURES: Spatiotemporal walking variables were assessed using accelerometers in the laboratory (baseline and posttraining assessments) and continuously at home during the training period. Variables included daily activity, walking speed, stride length, stride frequency, leg swing time, and gait asymmetry. Questionnaires including the 39-item Parkinson Disease Questionnaire (PDQ-39) were administered to determine self-reported change in walking, as well as feasibility. RESULTS: At posttraining assessment, only the gait observation group reported significantly improved mobility (PDQ-39). No improvements were seen in accelerometer-derived walking data. Participants found the at-home training tasks and accelerometer feasible to use. CONCLUSIONS: Participants found procedures feasible and reported improved mobility, suggesting that observational training holds promise in the rehabilitation of walking in PD. Observational training alone, however, may not be sufficient to enhance walking in PD. A more challenging and adaptive task, and the use of explicit perceptual learning and practice of actions, may be required to effect change. PMID- 26808784 TI - Carbon Monoxide-Assisted Synthesis of Ultrathin PtCu3 Alloy Wavy Nanowires and Their Enhanced Electrocatalysis. AB - Glucose sensing that is not influenced by the presence of chloride, uric acid, ascorbic acid and dopamine is achieved on ultrathin PtCu3 alloy wavy nanowires (WNWs). These WNWs are synthesized by a facile, one-pot, templateless hydrothermal method in an atmosphere of CO, which is critical to the formation process. Their structural properties, including the abundance of twinning defects, make the as-prepared PtCu3 WNWs excellent electrocatalysts for methanol oxidation as well as great sensors for glucose. PMID- 26808783 TI - Effect of Early Intensive Care on Recovery From Whiplash-Associated Disorders: Results of a Population-Based Cohort Study. AB - OBJECTIVE: To determine whether the results from previous research suggesting that early intensive health care delays recovery from whiplash-associated disorders (WADs) were confounded by expectations of recovery and whether the association between early health care intensity and time to recovery varies across patterns of health care. DESIGN: Population-based inception cohort. SETTING: All adults (>=18y) injured in motor vehicle collisions who received treatment from a regulated health professional or reported their injuries to the single provincially administered motor vehicle insurer. PARTICIPANTS: Participants with WAD (N=5204). Self-report visits to physicians, chiropractors, physiotherapists, massage therapists, and other professionals during the first 42 days postcollision were used to define health care intensity. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Self-perceived recovery. RESULTS: Individuals with high utilization health care had slower recovery independent of expectation of recovery and other confounders. Compared with individuals who reported low utilization of physician services, recovery was slower for those with high health care utilization, regardless of the type of profession. For instance, those with high physician (hazard rate ratio [HRR]=.56; 95% confidence interval [CI], .42 .75), physician and high physiotherapy utilization (HRR=.68; 95% CI, .61-.77), physician and high chiropractor utilization (HRR=.74; 95% CI, .64-.85), and physician and high massage therapy utilization (HRR=.78; 95% CI, .68-.90) had significantly slower recovery. CONCLUSIONS: Our study adds to the existing evidence that early intensive care is associated with slower recovery from WAD, independent of expectation of recovery. The results have policy implications and suggest that the optimal management of WADs focuses on reassurance and education instead of intensive care. PMID- 26808785 TI - Analysis on Soil Seed Bank Diversity Characteristics and Its Relation with Soil Physical and Chemical Properties after Substrate Addition. AB - AIMS: Considered as an essential measure in the application of soil seed bank (SSB) projects, the mixing of substrate and surface soil can effectively improve soil condition. This research is aimed at exploring the diversity characteristics of SSBs and the relationships between SSBs and soil properties. METHODS: Canonical correspondence analysis (CCA) was adopted to describe the ordination of SSBs on soil properties' gradients; multiple linear regressions were adopted to analyze the relationship between average growth height and soil properties, density and soil properties. RESULTS: Experimental groups of mixed substrate (the mixture of organic and inorganic substrates) had high diversity indexes, especially the Shannon-Wiener Index compared with those of single substrate. Meanwhile, a higher number of species and increased density were also noted in those of mixed substrate. The best test group, No.16, had the highest diversity indexes with a Shannon-Wiener of 1.898, Simpson of 0.633 and Pielou of 0.717, and also showed the highest density of 14000 germinants /m2 and 21 species. In addition, an improvement of the soil's chemical and physical properties was noted when the substrates were mixed. The mixed substrate of turfy soil and perlite could effectively enhance the soil moisture content, whilst a mixed substrate of rice husk carbon and vermiculite could improve the content of available potassium (AK) and phosphorus (AP) and strengthen soil fertility. The germinated plants also reflected obvious regularities of ordination on soil factor gradients. Three distinct cluster groups were presented, of which the first cluster was distributed in an area with a relatively higher content of AK and AP; the second cluster was distributed at places with relatively higher soil moisture content; and the third cluster of plants didn't show any obvious relationship with soil physical and chemical properties. Through CCA analysis, AK and AP were considered the most important soil factors to influence the SSB, which was illustrated in regression analysis with a high correlation coefficient when dependent values were growth height and density respectively. The linear regression equations with: growth height = 142.728 - 1.514TC + 30.218AP - 5.083TN + 10.839AK + 1.234mc; density = -68.216 - 4.609TC + 9.566AP - 35.492TN + 19.779AK - 1.591mc.were established by multiple linear regression. CONCLUSIONS: (1) The mixed substrates showed a greater advantage for SSBs than single substrates, both in improving the number of species, density and diversity indexes. (2) The germinated plants reflected an obvious preference to different soil conditions, which different mixed substrates could improve accordingly. (3) AK, AP were important soil factors to influence SSBs, especially in the growth of plants and density. PMID- 26808787 TI - Making a difference. PMID- 26808786 TI - Patient reported outcome measures in chronic obstructive pulmonary disease: Which to use? AB - Patient-reported outcomes (PROs), such as symptoms and perceived health status, are essential in chronic obstructive pulmonary disease (COPD) for determining disease severity, impact on daily life, effect of treatment and recovery from exacerbations. This field has evolved rapidly and there are a plethora of instruments assessing different PROs. The aim of this review is to provide an understanding of the concept of PROs in COPD. The PROs reflect important aspects of COPD which have a direct impact on daily life. Common symptoms such as dyspnea, cough, phlegm, anxiety, fatigue, and pain and as well as physical function and the risk for and occurrence of acute exacerbations should be assessed both in the clinic and in research. Besides impact on daily life, some of the PROs are related to disease progress and mortality. Construction of composite variables including different disease specific and generic PROs provide a general estimation of health status. PMID- 26808788 TI - Transformational leadership is for everyone. PMID- 26808789 TI - It's OK for you but maybe not for me: the challenge of putting medical education research findings and evidence into practice. PMID- 26808790 TI - Mindlines in a digital age. PMID- 26808791 TI - Selecting, training and assessing new general practice community teachers in UK medical schools. AB - BACKGROUND: Standards for undergraduate medical education in the UK, published in Tomorrow's Doctors, include the criterion 'everyone involved in educating medical students will be appropriately selected, trained, supported and appraised'. AIMS: To establish how new general practice (GP) community teachers of medical students are selected, initially trained and assessed by UK medical schools and establish the extent to which Tomorrow's Doctors standards are being met. METHOD: A mixed methods study with questionnaire data collected from 24 lead GPs at UK medical schools, 23 new GP teachers from two medical schools plus a semi-structured telephone interview with two GP leads. Quantitative data were analysed descriptively and qualitative data were analysed informed by framework analysis. RESULTS: GP teachers' selection is non-standardised. One hundred per cent of GP leads provide initial training courses for new GP teachers; 50% are mandatory. The content and length of courses varies. All GP leads use student feedback to assess teaching, but other required methods (peer review and patient feedback) are not universally used. CONCLUSIONS: To meet General Medical Council standards, medical schools need to include equality and diversity in initial training and use more than one method to assess new GP teachers. Wider debate about the selection, training and assessment of new GP teachers is needed to agree minimum standards. PMID- 26808792 TI - Commentary on 'Selecting, training and assessing new general practice community teachers in UK medical schools'. PMID- 26808793 TI - Peer-supported review of teaching: an evaluation. AB - Peer-supported review (also called peer observation) of teaching is a commonly implemented method of ascertaining teaching quality that supplements student feedback. A large variety of scheme formats with rather differing purposes are described in the literature. They range from purely formative, developmental formats that facilitate a tutor's reflection of their own teaching to reaffirm strengths and identify potential areas for development through to faculty- or institution-driven summative quality assurance-based schemes. Much of the current literature in this field focuses within general higher education and on the development of rating scales, checklists or observation tools to help guide the process. This study reports findings from a qualitative evaluation of a purely formative peer-supported review of teaching scheme that was implemented for general practice clinical tutors at our medical school and describes tutors' attitudes and perceived benefits and challenges when undergoing observation. PMID- 26808794 TI - Leadership skills teaching in Yorkshire & the Humber - a survey: uncovering, sharing, developing, embedding. AB - Medical leadership is a hot topic, but it is not known yet how to teach this most effectively. A working party of educators in Yorkshire and the Humber (Y&H) studied the leadership domains, as set out in the Medical Leadership Competency Framework and from this distilled a set of 'trainable' leadership skills, which were felt to be important to teach during general practitioner (GP) training. A questionnaire was sent out to a large GP educational community (educators and trainees) within Y&H to establish the following: (i) whether the distilled skills were thought to have face validity when applied to the concept of leadership, (ii) what was the relative importance of these skills in relation to each other and (iii) the degree to which these skills were already being taught in practice placements and at General Practice Specialty Training Programme (GPSTP) teaching sessions.Educators reported more teaching and training occurring than trainees reported receiving, and the relative importance of the skills sets were different between educators and trainees. It was evident that leadership skills are currently being taught, but that making training explicitly 'leadership', and raising the importance of leadership skills in GP, may address some of these imbalances. Educators requested guidance on how to teach these skills effectively and commented that many existing opportunities for leadership teaching and training are not well recognised or used. Routinely and regularly offering the chance for trainees at all levels to be exposed to leadership skills by role modelling, making use of everyday opportunities in practice to teach and encouraging trainee involvement in projects and opportunities to practice new skills can facilitate the acquisition and celebration of mastery of generic leadership skills. PMID- 26808795 TI - How do experienced GP trainers decide which of their trainees need to be referred to a more senior educator in the East Midlands Healthcare Workforce Deanery? AB - OBJECTIVE: To identify experienced trainers' reasons for considering and/or discussing concerns about GP trainees with their local Training Programme Director (TPD). METHOD: Interviews were carried out with fourteen trainers across Leicestershire and Northamptonshire who volunteered to assist in response to an email request sent out to trainers in these areas; twelve of these had more than five years' training experience. Grounded Theory Method (GTM), with a semi structured interview process as suggested by Corbin and Strauss, was used to analyse the transcripts. RESULTS: Experienced trainers find it difficult to explain their decision-making in keeping with the Dreyfus Expertise Model; they use their willingness to choose the doctor as their personal doctor, predating the UK Government's 'Friends and Family Test', as well as their experience in consulting and referring patients as concepts which help the decision. For less experienced trainers, the Milton Keynes Traffic Light System was identified as a tool that might help decision-making. CONCLUSIONS: Experienced trainers recognised underperformance and possible underlying causes. The triggers for discussion with TPDs were viewing the trainee either as someone 'they would not like to be their family doctor' or as 'a patient whose problem needed referral to a specialist'. This was done at an 'expert' level. It was sometimes difficult for the trainers to define the processes they used. Less-experienced trainers found that a tool such as the Milton Keynes Traffic Light System was a useful aid. PMID- 26808796 TI - Want to make didactics more engaging: don't forget to use a hook! PMID- 26808797 TI - GP training for patient safety: understanding, classifying and mapping. PMID- 26808798 TI - Fostering resilience with GPs: a workshop approach. PMID- 26808799 TI - Tips on inductive learning and building resilience. PMID- 26808800 TI - The audio-COT (consultation observation tool): developing a new assessment tool for GP training. PMID- 26808801 TI - Reflection. PMID- 26808802 TI - Overcoming challenges in primary care education: stories from Rwanda. PMID- 26808803 TI - The desired Rwandan health care provider: development and delivery of undergraduate social and community medicine training. PMID- 26808804 TI - Twinning Ph.D. students from south and north: towards equity in collaborative research. PMID- 26808806 TI - Learning from a GP exchange to France. PMID- 26808805 TI - Manage the emotional needs of learners in teaching sessions. PMID- 26808808 TI - The need to lead - a newly qualified GP's perspective. PMID- 26808807 TI - A standardised questionnaire for evaluating hospital-based rotations for general practice vocational training. PMID- 26808809 TI - Attitudes and experiences of GP trainees towards undergraduate teaching: An underused resource? PMID- 26808810 TI - The geography of General Practice vocational training schemes in the UK. PMID- 26808811 TI - Carbonylmetallates--A Special Family of Nucleophiles in Aromatic and Vinylic Substitution Reactions. AB - Carbonylmetallates, [M(CO)(n)L](-), anionic transition-metal carbonyl complexes, represent a large family of metal-centered nucleophiles, and studying carbonylmetallates allows us to understand the differences in the behavior of the metal-centered complexes versus heteroatom-based nucleophiles. The mechanisms of carbonylmetallate reactions with aryl- and alkenyl halides have been examined by employing radical and, especially, carbanion trapping techniques. Carbonylmetallates show a marked preference for halogenophilic attack, and nucleophilic substitution with carbonylmetallates is often not a direct process, but proceeds through the initial attack at halogen with subsequent coupling of carbanion and HalM(CO)(n)L intermediates. Factors governing the competition between the halogenophilic and more common "carbophilic" reaction pathways, as well as the means of predicting the actual course of reaction are discussed. The review also considers other aspects of carbonylmetallate reactivity, including ion-pairing effects, radical-mediated nucleophilic substitution pathways, and the carbonylmetallate nucleophilicity scale in the reactions with pi-electrophiles. PMID- 26808812 TI - Impact of Genetic Reduction of NMNAT2 on Chemotherapy-Induced Losses in Cell Viability In Vitro and Peripheral Neuropathy In Vivo. AB - Nicotinamide mononucleotide adenylyl transferases (NMNATs) are essential neuronal maintenance factors postulated to preserve neuronal function and protect against axonal degeneration in various neurodegenerative disease states. We used in vitro and in vivo approaches to assess the impact of NMNAT2 reduction on cellular and physiological functions induced by treatment with a vinca alkaloid (vincristine) and a taxane-based (paclitaxel) chemotherapeutic agent. NMNAT2 null (NMNAT2-/-) mutant mice die at birth and cannot be used to probe functions of NMNAT2 in adult animals. Nonetheless, primary cortical cultures derived from NMNAT2-/- embryos showed reduced cell viability in response to either vincristine or paclitaxel treatment whereas those derived from NMNAT2 heterozygous (NMNAT2+/-) mice were preferentially sensitive to vincristine-induced degeneration. Adult NMNAT2+/- mice, which survive to adulthood, exhibited a 50% reduction of NMNAT2 protein levels in dorsal root ganglia relative to wildtype (WT) mice with no change in levels of other NMNAT isoforms (NMNAT1 or NMNAT3), NMNAT enzyme activity (i.e. NAD/NADH levels) or microtubule associated protein-2 (MAP2) or neurofilament protein levels. We therefore compared the impact of NMNAT2 knockdown on the development and maintenance of chemotherapy-induced peripheral neuropathy induced by vincristine and paclitaxel treatment using NMNAT2+/- and WT mice. NMNAT2+/- did not differ from WT mice in either the development or maintenance of either mechanical or cold allodynia induced by either vincristine or paclitaxel treatment. Intradermal injection of capsaicin, the pungent ingredient in hot chili peppers, produced equivalent hypersensitivity in NMNAT2+/- and WT mice receiving vehicle in lieu of paclitaxel. Capsaicin-evoked hypersensitivity was enhanced by prior paclitaxel treatment but did not differ in either NMNAT2+/- or WT mice. Thus, capsaicin failed to unmask differences in nociceptive behaviors in either paclitaxel-treated or paclitaxel-untreated NMNAT2+/- and WT mice. Moreover, no differences in motor behavior were detected between genotypes in the rotarod test. Our studies do not preclude the possibility that complete knockout of NMNAT2 in a conditional knockout animal could unmask a role for NMNAT2 in protection against detrimental effects of chemotherapeutic treatment. PMID- 26808813 TI - Accurate Identification of Common Pathogenic Nocardia Species: Evaluation of a Multilocus Sequence Analysis Platform and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry. AB - Species identification of Nocardia is not straightforward due to rapidly evolving taxonomy, insufficient discriminatory power of conventional phenotypic methods and also of single gene locus analysis including 16S rRNA gene sequencing. Here we evaluated the ability of a 5-locus (16S rRNA, gyrB, secA1, hsp65 and rpoB) multilocus sequence analysis (MLSA) approach as well as that of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) in comparison with sequencing of the 5'-end 606 bp partial 16S rRNA gene to provide identification of 25 clinical isolates of Nocardia. The 5'-end 606 bp 16S rRNA gene sequencing successfully assigned 24 of 25 (96%) clinical isolates to species level, namely Nocardia cyriacigeorgica (n = 12, 48%), N. farcinica (n = 9, 36%), N. abscessus (n = 2, 8%) and N. otitidiscaviarum (n = 1, 4%). MLSA showed concordance with 16S rRNA gene sequencing results for the same 24 isolates. However, MLSA was able to identify the remaining isolate as N. wallacei, and clustered N. cyriacigeorgica into three subgroups. None of the clinical isolates were correctly identified to the species level by MALDI-TOF MS analysis using the manufacturer-provided database. A small "in-house" spectral database was established incorporating spectra of five clinical isolates representing the five species identified in this study. After complementation with the "in-house" database, of the remaining 20 isolates, 19 (95%) were correctly identified to species level (score >= 2.00) and one (an N. abscessus strain) to genus level (score >= 1.70 and < 2.00). In summary, MLSA showed superior discriminatory power compared with the 5'-end 606 bp partial 16S rRNA gene sequencing for species identification of Nocardia. MALDI-TOF MS can provide rapid and accurate identification but is reliant on a robust mass spectra database. PMID- 26808814 TI - Use of the over-the-scope clip to treat massive bleeding at the transitional zone of the anal canal: a case series. AB - BACKGROUND AND AIMS: Endoscopic treatment of anorectal bleeding can be challenging. We report use of the endoscopic over-the-scope clip (OTSC) to treat massive bleeding from the transitional zone of the anorectum. The aim of this retrospective study was to assess the clinical outcome and efficacy of the OTSC and to describe the technique of its use in acute severe bleeding occurring at the transitional zone of the anorectum. METHODS: We treated 5 consecutive patients (age range, 36-79 years, 5 men) with severe bleeding from the transitional zone of the anorectum caused by hemorrhoid therapy, digital trauma, and a Dieulafoy lesion. We analyzed the efficacy, safety, and outcome of endoscopic treatment using the OTSC. RESULTS: Primary hemostasis was successfully achieved in all the patients using a single OTSC. The OTSC deployment technique was adapted from the endoscopic band ligation of hemorrhoids. There was no immediate or late rebleeding. We observed that there were no adverse events from OTSC placement in the anorectum. CONCLUSIONS: This case series provides evidence that OTSCs may be effective in controlling bleeding from the transitional zone of the anorectum. Although use of OTSCs for bleeding elsewhere in the GI tract has been described, this case series is the first to show its application in the transitional zone of the anorectum. PMID- 26808815 TI - RNA sequencing distinguishes benign from malignant pancreatic lesions sampled by EUS-guided FNA. AB - BACKGROUND AND AIMS: EUS-guided FNA (EUS-FNA) is the primary method used to obtain pancreatic tissue for preoperative diagnosis. Accumulating evidence suggests diagnostic and prognostic information may be obtained by gene-expression profiling of these biopsy specimens. RNA sequencing (RNAseq) is a newer method of gene-expression profiling, but published data are scant on the use of this method on pancreas tissue obtained via EUS-FNA. The aim of this study was to determine whether RNAseq of EUS-FNA biopsy samples of undiagnosed pancreatic masses can reliably discriminate between benign and malignant tissue. METHODS: In this prospective study, consenting adults presented to 2 tertiary care hospitals for EUS of suspected pancreatic mass. Tissue was submitted for RNAseq. The results were compared with cytologic diagnosis, surgical pathology diagnosis, or benign clinical follow-up of at least 1 year. RESULTS: Forty-eight patients with solid pancreatic mass lesions were enrolled. Nine samples were excluded because of inadequate RNA and 3 because of final pathologic diagnosis of neuroendocrine tumor. Data from the first 13 patients were used to construct a linear classifier, and this was tested on the final 23 patients (15 malignant and 8 benign lesions). RNAseq of EUS-FNA biopsy samples distinguishes ductal adenocarcinoma from benign pancreatic solid masses with a sensitivity of .87 (range, .58-.98) and specificity of .75 (range, .35-.96). CONCLUSIONS: This proof of-principle study suggests RNAseq of EUS-FNA samples can reliably detect adenocarcinoma and may provide a new method to evaluate more diagnostically challenging pancreatic lesions. PMID- 26808816 TI - Inhibition of Fatty Acid Synthase Decreases Expression of Stemness Markers in Glioma Stem Cells. AB - Cellular metabolic changes, especially to lipid metabolism, have recently been recognized as a hallmark of various cancer cells. However, little is known about the significance of cellular lipid metabolism in the regulation of biological activity of glioma stem cells (GSCs). In this study, we examined the expression and role of fatty acid synthase (FASN), a key lipogenic enzyme, in GSCs. In the de novo lipid synthesis assay, GSCs exhibited higher lipogenesis than differentiated non-GSCs. Western blot and immunocytochemical analyses revealed that FASN is strongly expressed in multiple lines of patient-derived GSCs (G144 and Y10), but its expression was markedly reduced upon differentiation. When GSCs were treated with 20 MUM cerulenin, a pharmacological inhibitor of FASN, their proliferation and migration were significantly suppressed and de novo lipogenesis decreased. Furthermore, following cerulenin treatment, expression of the GSC markers nestin, Sox2 and fatty acid binding protein (FABP7), markers of GCSs, decreased while that of glial fibrillary acidic protein (GFAP) expression increased. Taken together, our results indicate that FASN plays a pivotal role in the maintenance of GSC stemness, and FASN-mediated de novo lipid biosynthesis is closely associated with tumor growth and invasion in glioblastoma. PMID- 26808817 TI - Internet-Delivered Disease Management for Recurrent Depression: A Multicenter Randomized Controlled Trial. AB - BACKGROUND: Strategies to improve the life of patients suffering from recurrent major depression have a high relevance. This study examined the efficacy of 2 Internet-delivered augmentation strategies that aim to prolong symptom-free intervals. METHODS: Efficacy was tested in a 3-arm, multicenter, open-label, evaluator-blind, randomized controlled trial. Upon discharge from inpatient mental health care, 232 adults with 3 or more major depressive episodes were randomized to 1 of 2 intervention groups (SUMMIT or SUMMIT-PERSON) or to treatment as usual (TAU) alone. Over 12 months, participants in both intervention arms received, in addition to TAU, intense monitoring via e-mail or a smartphone, including signaling of upcoming crises, assistance with personal crisis management, and facilitation of early intervention. SUMMIT-PERSON additionally offered regular expert chats. The primary outcome was 'well weeks', i.e. weeks with at most mild symptoms assessed by the Longitudinal Interval Follow-Up Evaluation, during 24 months after the index treatment. RESULTS: SUMMIT compared to TAU reduced the time with an unwell status (OR 0.48; 95% CI 0.23-0.98) through faster transitions from unwell to well (OR 1.44; 95% CI 0.83-2.50) and slower transitions from well to unwell (OR 0.69; 95% CI 0.44-1.09). Contrary to the hypothesis, SUMMIT-PERSON was not superior to either SUMMIT (OR 0.77; 95% CI 0.38 1.56) or TAU (OR 0.62; 95% CI 0.31-1.24). The efficacy of SUMMIT was strongest 8 months after the intervention. CONCLUSIONS: The fully automated Internet delivered augmentation strategy SUMMIT has the potential to improve TAU by reducing the lifelong burden of patients with recurrent depression. The fact that the effects wear off suggests a time-unlimited extension. PMID- 26808818 TI - Reply to Dr. Leon: true but unrelated. PMID- 26808819 TI - Pathophysiology and clinical trials have limitations in some areas of medicine: focus on psychiatry (letter commenting: J Clin Epidemiol. 2014;67(4):361-363.). PMID- 26808820 TI - Bioecological Drivers of Rabies Virus Circulation in a Neotropical Bat Community. AB - INTRODUCTION: In addition to the commonly accepted importance of the vampire bat in the maintenance and transmission of the rabies virus (RABV) in South America, RABV infection of other species is widely evidenced, challenging their role in the viral cycle. METHODOLOGY / PRINCIPLES FINDINGS: To identify the bioecological drivers of RABV circulation in neotropical bat communities, we conducted a molecular and serological survey on almost 1,000 bats from 30 species, and a 4 year longitudinal survey in two colonies of vampire bats in French Guiana. RABV was molecularly detected in a common vampire and in a frugivorous bat. The sequences corresponded to haematophagous bat-related strains and were close to viruses circulating in the Brazilian Amazon region. Species' seroprevalence ranged from 0 to 20%, and the risk of seropositivity was higher in bats with a haematophagous diet, living in monospecific colonies and in dense forests. The longitudinal survey showed substantial temporal fluctuations, with individual waves of seroconversions and waning immunity. The high prevalences observed in bat communities, in most habitats and in species that do not share the same microhabitats and bioecological patterns, the temporal variations, and a rather short period of detectable antibodies as observed in recaptured vampires suggest (i) frequent exposure of animals, (ii) an ability of the infected host to control and eliminate the virus, (iii) more relaxed modes of exposure between bats than the commonly assumed infection via direct contact with saliva of infected animals, all of which should be further investigated. CONCLUSIONS / SIGNIFICANCE: We hypothesize that RABV circulation in French Guiana is mainly maintained in the pristine forest habitats that may provide sufficient food resources to allow vampire bats, the main prevalent species, to survive and RABV to be propagated. However, on the forest edge and in disturbed areas, human activities may induce more insidious effects such as defaunation. One of the ecological consequences is the disappearance of resources for tertiary or secondary consumers. Populations of vampires may then shift to alternative resources such as cattle, domestic animals and humans. Therefore, a good forest status, allowing both a dilution effect in highly rich bat communities and the maintenance of large populations of medium-sized and large mammals used as prey by vampires, should prevent their migration to anthropized areas. PMID- 26808821 TI - Comprehensive curation and analysis of fungal biosynthetic gene clusters of published natural products. AB - Microorganisms produce a wide range of natural products (NPs) with clinically and agriculturally relevant biological activities. In bacteria and fungi, genes encoding successive steps in a biosynthetic pathway tend to be clustered on the chromosome as biosynthetic gene clusters (BGCs). Historically, "activity-guided" approaches to NP discovery have focused on bioactivity screening of NPs produced by culturable microbes. In contrast, recent "genome mining" approaches first identify candidate BGCs, express these biosynthetic genes using synthetic biology methods, and finally test for the production of NPs. Fungal genome mining efforts and the exploration of novel sequence and NP space are limited, however, by the lack of a comprehensive catalog of BGCs encoding experimentally-validated products. In this study, we generated a comprehensive reference set of fungal NPs whose biosynthetic gene clusters are described in the published literature. To generate this dataset, we first identified NCBI records that included both a peer reviewed article and an associated nucleotide record. We filtered these records by text and homology criteria to identify putative NP-related articles and BGCs. Next, we manually curated the resulting articles, chemical structures, and protein sequences. The resulting catalog contains 197 unique NP compounds covering several major classes of fungal NPs, including polyketides, non ribosomal peptides, terpenoids, and alkaloids. The distribution of articles published per compound shows a bias toward the study of certain popular compounds, such as the aflatoxins. Phylogenetic analysis of biosynthetic genes suggests that much chemical and enzymatic diversity remains to be discovered in fungi. Our catalog was incorporated into the recently launched Minimum Information about Biosynthetic Gene cluster (MIBiG) repository to create the largest known set of fungal BGCs and associated NPs, a resource that we anticipate will guide future genome mining and synthetic biology efforts toward discovering novel fungal enzymes and metabolites. PMID- 26808822 TI - "Immunonutrition" Has Failed to Improve Peritonitis-Induced Septic Shock in Rodents. AB - BACKGROUND: Immunonutrition in sepsis, including n-3 poly-unsaturated fatty acids (PUFAs) or L-arginine supplementation, is a controversial issue that has yielded a great number of studies for the last thirty-five years, and the conclusions regarding the quantity and quality of this support in patients are deceiving. The aim of the present experimental study is to investigate the effects of a pretreatment with enteral nutrition enriched with n-3 PUFAs or L-arginine on vascular dysfunctions, inflammation and oxidative stress during septic shock in rats. DESIGN: Rats were fed with enteral Peptamen(r) HN (HN group), Peptamen(r) AF containing n-3 PUFAs (AF group) or Peptamen(r) AF enriched with L-arginine (AFA group). On day 4, peritonitis by cecal ligation and puncture (CLP) was performed. Rats were resuscitated (H18) once septic shock was established. After a 4-hour resuscitation, vessels and organs were harvested to assess inflammation, superoxide anion, nitric oxide and prostacyclin levels. Ex-vivo vascular reactivity was also performed. RESULTS: Compared to CLP-AF or CLP-HN groups, 47.6% of CLP-AFA rats died before the beginning of hemodynamic measurements (vs. 8.0% and 20.0% respectively, p<0.05). AF and AFA rats required significantly increased norepinephrine infusion rates to reach the mean arterial pressure objective, compared to CLP-HN rats. Both CLP-AF and CLP-AFA reduced mesenteric resistance arterial contractility, decreased vascular oxidative stress, but increased NF-kappaB (0.40+/-0.15 in CLP-AF and 0.69+/-0.06 in CLP-AFA vs. 0.09+/ 0.03 in SHAM rats and 0.30+/-0.06 in CLP-HN, beta-actin ratio, p<0.05) and pIkappaB expression (0.60+/-0.03 in CLP-AF and 0.94+/-0.15 in CLP-AFA vs. 0.04+/ 0.01 in SHAM rats and 0.56+/-0.07 in CLP-HN, beta-actin ratio, p<0.05), nitric oxide and prostacyclin production in septic rats. CONCLUSIONS: Although n-3 PUFAs or L-arginine supplementation exhibited an antioxidant effect, it worsened the septic shock-induced vascular dysfunction. Furthermore, mortality was higher after L-arginine supplementation. PMID- 26808823 TI - Identification of Immunogenic Cytotoxic T Lymphocyte Epitopes Containing Drug Resistance Mutations in Antiretroviral Treatment-Naive HIV-Infected Individuals. AB - BACKGROUND: Therapeutic HIV vaccines may prove helpful to intensify antiretroviral treatment (ART) efficacy and may be an integral part of future cure strategies. METHODS: We examined IFN-gamma ELISpot responses to a panel of 218 HIV clade B consensus-based HIV protease-reverse transcriptase peptides, designed to mimic previously described and predicted cytotoxic T lymphocyte epitopes overlapping drug resistance (DR) positions, that either included the consensus sequence or the DR variant sequence, in 49 ART-naive HIV-infected individuals. Next generation sequencing was used to assess the presence of minority DR variants in circulating viral populations. RESULTS: Although a wide spectrum of differential magnitudes of response to DR vs. WT peptide pairs was observed, responses to DR peptides were frequent and strong in the study cohort. No difference between the median magnitudes of response to DR vs. WT peptides was observed. Interestingly, of the 22 peptides that were recognized by >15% of the participants, two-thirds (64%) corresponded to DR peptides. When analysing responses per peptide pair per individual, responses to only WT (median 4 pairs/individual) or DR (median 6 pairs/individual) were more common than responses to both WT and DR (median 2 pairs/individual; p<0.001). While the presence of ELISpot responses to WT peptides was frequently associated with the presence of the corresponding peptide sequence in the patient's virus (mean 68% of cases), responses to DR peptides were generally not associated with the presence of DR mutations in the viral population, even at low frequencies (mean 1.4% of cases; p = 0.0002). CONCLUSIONS: Our data suggests that DR peptides are frequently immunogenic and raises the potential benefit of broadening the antigens included in a therapeutic vaccine approach to immunogenic epitopes containing common DR sequences. Further studies are needed to assess the quality of responses elicited by DR peptides. PMID- 26808825 TI - Correction: Hepatocyte-Specific Depletion of UBXD8 Induces Periportal Steatosis in Mice Fed a High-Fat Diet. PMID- 26808824 TI - Unexpected Decrease in Milk Production after Fenbendazole Treatment of Dairy Cows during Early Grazing Season. AB - Gastrointestinal nematodes (GIN) infection can impair milk production (MP) in dairy cows. To investigate whether MP would be optimized by spring targeted selective anthelmintic treatment in grazing cows, we assessed (1) the effect on MP of an anthelmintic treatment applied 1.5 to 2 months after turn-out, and (2) herd and individual indicators associated with the post-treatment MP response. A randomized controlled clinical trial was conducted in 13 dairy farms (578 cows) in western France in spring 2012. In each herd, lactating cows of the treatment group received fenbendazole orally, control cows remained untreated. Daily cow MP was recorded from 2 weeks before until 15 weeks after treatment. Individual serum pepsinogen and anti-Ostertagia antibody levels (expressed as ODR), faecal egg count and bulk tank milk (BTM) Ostertagia ODR were measured at treatment time. Anthelmintic treatment applied during the previous housing period was recorded for each cow. In each herd, information regarding heifers' grazing and anthelmintic treatment history was collected to assess the Time of Effective Contact (TEC, in months) with GIN infective larvae before the first calving. The effect of treatment on weekly MP averages and its relationships with herd and individual indicators were studied using linear mixed models with two nested random effects (cow within herd). Unexpectedly, spring treatment had a significant detrimental effect on MP (-0.92 kg/cow/day on average). This negative MP response was particularly marked in high producing cows, in cows not treated during the previous housing period or with high pepsinogen levels, and in cows from herds with a high TEC or a high BTM ODR. This post-treatment decrease in MP may be associated with immuno-inflammatory mechanisms. Until further studies can assess whether this unexpected result can be generalized, non-persistent treatment of immunized adult dairy cows against GIN should not be recommended in early grazing season. PMID- 26808826 TI - Uniform Incorporation of Flocculent Molybdenum Disulfide Nanostructure into Three Dimensional Porous Graphene as an Anode for High-Performance Lithium Ion Batteries and Hybrid Supercapacitors. AB - Hybrid supercapacitors (HSCs) with lithium-ion battery-type anodes and electric double layer capacitor-type cathodes are attracting extensive attention and under wide investigation because of their combined merits of both high power and energy density. However, the performance of most HSCs is limited by low kinetics of the battery-type anode which cannot match the fast kinetics of the capacitor-type cathode. In this study, we have synthesized a three-dimensional (3D) porous composite with uniformly incorporated MoS2 flocculent nanostructure onto 3D graphene via a facile solution-processed method as an anode for high-performance HSCs. This composite shows significantly enhanced electrochemical performance due to the synergistic effects of the conductive graphene sheets and the interconnected porous structure, which exhibits a high rate capability of 688 mAh/g even at a high current density of 8 A/g and a stable cycling performance (997 mAh/g after 700 cycles at 2 A/g). Furthermore, by using this composite as the anode for HSCs, the HSC shows a high energy density of 156 Wh/kg at 197 W/kg, which also remains at 97 Wh/kg even at a high power density of 8314 W/kg with a stable cycling life, among the best results of the reported HSCs thus far. PMID- 26808828 TI - Errata. AB - Misspelled Author Name in the Article by Neogi et al (Arthritis Rheumatol, October 2015). PMID- 26808829 TI - Errata. AB - Errors in Table 3 and 4 of the Article by Solomon et al (Arthritis Rheumatol, August 2015). PMID- 26808827 TI - The American College of Rheumatology Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis. AB - OBJECTIVE: Early diffuse cutaneous systemic sclerosis (dcSSc) is characterized by rapid changes in the skin and internal organs. The objective of this study was to develop a composite response index in dcSSc (CRISS) for use in randomized controlled trials (RCTs). METHODS: We developed 150 paper patient profiles with standardized clinical outcome elements (core set items) using patients with dcSSc. Forty scleroderma experts rated 20 patient profiles each and assessed whether each patient had improved or not improved over a period of 1 year. Using the profiles for which raters had reached a consensus on whether the patients were improved versus not improved (79% of the profiles examined), we fit logistic regression models in which the binary outcome referred to whether the patient was improved or not, and the changes in the core set items from baseline to followup were entered as covariates. We tested the final index in a previously completed RCT. RESULTS: Sixteen of 31 core items were included in the patient profiles after a consensus meeting and review of test characteristics of patient-level data. In the logistic regression model in which the included core set items were change over 1 year in the modified Rodnan skin thickness score, the forced vital capacity, the patient and physician global assessments, and the Health Assessment Questionnaire disability index, sensitivity was 0.982 (95% confidence interval 0.982-0.983) and specificity was 0.931 (95% confidence interval 0.930-0.932), and the model with these 5 items had the highest face validity. Subjects with a significant worsening of renal or cardiopulmonary involvement were classified as not improved, regardless of improvements in other core items. With use of the index, the effect of methotrexate could be differentiated from the effect of placebo in a 1-year RCT (P = 0.02). CONCLUSION: We have developed a CRISS that is appropriate for use as an outcome assessment in RCTs of early dcSSc. PMID- 26808830 TI - Brief Report: Severe Inflammation Following Vaccination Against Streptococcus pneumoniae in Patients With Cryopyrin-Associated Periodic Syndromes. AB - OBJECTIVE: Pneumococcal vaccination is recommended for patients receiving immunosuppressive drugs. We describe unusually severe adverse reactions to pneumococcal vaccination in each of 7 consecutive patients with cryopyrin associated periodic syndromes (CAPS). METHODS: Seven consecutive patients with CAPS were vaccinated with pneumococcal polysaccharide or conjugate vaccines. Clinical information was collected retrospectively. RESULTS: Within a few hours after the vaccination, all 7 patients developed severe local reactions at the injection site. Two patients had to be hospitalized for systemic reactions including fever. All symptoms resolved in a period of 3-17 days. CONCLUSION: Our findings indicate that pneumococcal vaccines can trigger a severe local and systemic inflammatory reaction in patients with CAPS and possibly patients with other autoinflammatory diseases. Careful consideration is warranted when implementing current European League Against Rheumatism immunization guidelines in this patient population. PMID- 26808831 TI - The 'de novo' DNA methyltransferase Dnmt3b compensates the Dnmt1-deficient intestinal epithelium. AB - Dnmt1 is critical for immediate postnatal intestinal development, but is not required for the survival of the adult intestinal epithelium, the only rapidly dividing somatic tissue for which this has been shown. Acute Dnmt1 deletion elicits dramatic hypomethylation and genomic instability. Recovery of DNA methylation state and intestinal health is dependent on the de novo methyltransferase Dnmt3b. Ablation of both Dnmt1 and Dnmt3b in the intestinal epithelium is lethal, while deletion of either Dnmt1 or Dnmt3b has no effect on survival. These results demonstrate that Dnmt1 and Dnmt3b cooperate to maintain DNA methylation and genomic integrity in the intestinal epithelium. PMID- 26808832 TI - Estrogen Receptor Alpha (ESR1)-Dependent Regulation of the Mouse Oviductal Transcriptome. AB - Estrogen receptor-alpha (ESR1) is an important transcriptional regulator in the mammalian oviduct, however ESR1-dependent regulation of the transcriptome of this organ is not well defined, especially at the genomic level. The objective of this study was therefore to investigate estradiol- and ESR1-dependent regulation of the transcriptome of the oviduct using transgenic mice, both with (ESR1KO) and without (wild-type, WT) a global deletion of ESR1. Oviducts were collected from ESR1KO and WT littermates at 23 days of age, or ESR1KO and WT mice were treated with 5 IU PMSG to stimulate follicular development and the production of ovarian estradiol, and the oviducts collected 48 h later. RNA extracted from whole oviducts was hybridized to Affymetrix Genechip Mouse Genome 430-2.0 arrays (n = 3 arrays per genotype and treatment) or reverse transcribed to cDNA for analysis of the expression of selected mRNAs by real-time PCR. Following microarray analysis, a statistical two-way ANOVA and pairwise comparison (LSD test) revealed 2428 differentially expressed transcripts (DEG's, P < 0.01). Genotype affected the expression of 2215 genes, treatment (PMSG) affected the expression of 465 genes, and genotype x treatment affected the expression of 438 genes. With the goal of determining estradiol/ESR1-regulated function, gene ontology (GO) and bioinformatic pathway analyses were performed on DEG's in the oviducts of PMSG treated ESR1KO versus PMSG-treated WT mice. Significantly enriched GO molecular function categories included binding and catalytic activity. Significantly enriched GO cellular component categories indicated the extracellular region. Significantly enriched GO biological process categories involved a single organism, modulation of a measurable attribute and developmental processes. Bioinformatic analysis revealed ESR1-regulation of the immune response within the oviduct as the primary canonical pathway. In summary, a transcriptomal profile of estradiol- and ESR1-regulated gene expression and related bioinformatic analysis is presented to increase our understanding of how estradiol/ESR1 affects function of the oviduct, and to identify genes that may be proven as important regulators of fertility in the future. PMID- 26808833 TI - Coupling News Sentiment with Web Browsing Data Improves Prediction of Intra-Day Price Dynamics. AB - The new digital revolution of big data is deeply changing our capability of understanding society and forecasting the outcome of many social and economic systems. Unfortunately, information can be very heterogeneous in the importance, relevance, and surprise it conveys, affecting severely the predictive power of semantic and statistical methods. Here we show that the aggregation of web users' behavior can be elicited to overcome this problem in a hard to predict complex system, namely the financial market. Specifically, our in-sample analysis shows that the combined use of sentiment analysis of news and browsing activity of users of Yahoo! Finance greatly helps forecasting intra-day and daily price changes of a set of 100 highly capitalized US stocks traded in the period 2012 2013. Sentiment analysis or browsing activity when taken alone have very small or no predictive power. Conversely, when considering a news signal where in a given time interval we compute the average sentiment of the clicked news, weighted by the number of clicks, we show that for nearly 50% of the companies such signal Granger-causes hourly price returns. Our result indicates a "wisdom-of-the-crowd" effect that allows to exploit users' activity to identify and weigh properly the relevant and surprising news, enhancing considerably the forecasting power of the news sentiment. PMID- 26808834 TI - Brief Questionnaire Derived from PANSS Using a General Probability Model to Assess and Monitor the Clinical Features of Schizophrenia. AB - AIM: Patients with schizophrenia require continuous treatment much longer than the duration of their hospitalization, which makes their family members essential in their medical care. However, the evaluation of the disease state could only be done by professionals. This prompted us to seek potent indicators of disease states that are understandable and easy to use for the patients' family. METHOD: Specific items were firstly extracted from the total PANSS scale. Then 3 096 PANSS scores were analyzed using a nonlinear mixed-effects model (NONMEM). A questionnaire was subsequently developed for family members to assess and monitor the overall severity of schizophrenia. Finally this questionnaire was validated in 33 patients. RESULTS: 2 items (P1 and N4) were extracted from the 8 effective remission items according to the correlation coefficients between the total PANSS score and different combinations of items. P1N4 was defined as the sum of these 2 items. A model was then developed to describe the probability of PANSS>=60, with P1N4 as indicators. The results indicated that P1N4 could make a good predictor of the overall probability of PANSS>=60, which was independent of treatment. A brief questionnaire with 7 questions was developed based on the results. External validation results indicated the questionnaire's suitability for a good assessment. CONCLUSION: Questionnaire developed based on P1 and N4 may facilitate the patients' family members to better understand the disease state and help to prevent relapse. PMID- 26808836 TI - Dissipation of Fungicide Residues during Winemaking and Their Effects on Fermentation and the Volatile Composition of Wines. AB - The effects of four fungicides commonly used for the control of fungal diseases in vines and grapes in the course of winemaking were tested. The concentration of fungicide residues was monitored throughout the process to establish their kinetics of dissipation. In all cases the percentages of dissipation were >68%, which shows the detoxificant effect of the winemaking process. On the other hand, the effect of the fungicide residues on the aroma composition of Tempranillo red wines was tested. To evaluate possible modifications on the aroma profile of wines, seven odorant series (ripe fruits, fresh fruits, lactic, floral, spicy, vinous, and herbaceous) were built from the odor activity values (OAVs) obtained for each volatile compound. Ripe fruits and fresh fruits were the major aromatic attributes in all Tempranillo red wines. These two odorant series registered the highest variations in their total OAVs with respect to the control wine, especially with the application of boscalid + kresoxim-methyl into vines, leading to a decrease in the ripe fruit and fresh fruit nuances of the resulting wines. Moreover, when the effect of these fungicides on the aroma of Tempranillo red wines was compared throughout two years (2012 and 2013), wines elaborated from grapes treated in the field with boscalid + kresoxim-methyl in 2013 displayed the highest variation in aroma profile with respect to control wine. PMID- 26808835 TI - Optical Imaging of PARP1 in Response to Radiation in Oral Squamous Cell Carcinoma. AB - Targeting and inhibiting DNA repair pathways is a powerful strategy of controlling malignant growth. One such strategy includes the inhibition of PARP1, a central element in the intracellular DNA damage response. To determine and visualize the expression and intercellular distribution of PARP1 in vivo, and to monitor the pharmacokinetics of PARP1 targeted therapeutics, fluorescent small probes were developed. To date, however, it is unclear how these probes behave in a more realistic clinical setting, where DNA damage has been induced through one or more prior lines of therapy. Here, we use one such imaging agent, PARPi-FL, in tissues both with and without prior DNA damage, and investigate its value as a probe for PARP1 imaging. We show that PARP1 expression in oral cancer is high, and that the uptake of PARPi-FL is selective, irrespective of whether cells were exposed to irradiation or not. We also show that PARPi-FL uptake increases in response to DNA damage, and that this increase is reflected in higher enzyme expression. Our findings provide a framework for measuring exposure of cells to external beam radiation, and could help to elucidate the effects of such treatments non-invasively in mouse models of cancer. PMID- 26808837 TI - Development of an Arthroscopic Joint Capsule Injury Model in the Canine Shoulder. AB - BACKGROUND: The natural history of rotator cuff tears can be unfavorable as patients develop fatty infiltration and muscle atrophy that is often associated with a loss of muscle strength and shoulder function. To facilitate study of possible biologic mechanisms involved in early degenerative changes to rotator cuff muscle and tendon tissues, the objective of this study was to develop a joint capsule injury model in the canine shoulder using arthroscopy. METHODS: Arthroscopic surgical methods for performing a posterior joint capsulectomy in the canine shoulder were first defined in cadavers. Subsequently, one canine subject underwent bilateral shoulder joint capsulectomy using arthroscopy, arthroscopic surveillance at 2, 4 and 8 weeks, and gross and histologic examination of the joint at 10 weeks. RESULTS: The canine subject was weight bearing within eight hours after index and follow-up surgeries and had no significant soft tissue swelling of the shoulder girdle or gross lameness. Chronic synovitis and macroscopic and microscopic evidence of pathologic changes to the rotator cuff bony insertions, tendons, myotendinous junctions and muscles were observed. CONCLUSIONS: This study demonstrates feasibility and proof-of concept for a joint capsule injury model in the canine shoulder. Future work is needed to define the observed pathologic changes and their role in the progression of rotator cuff disease. Ultimately, better understanding of the biologic mechanisms of early progression of rotator cuff disease may lead to clinical interventions to halt or slow this process and avoid the more advanced and often irreversible conditions of large tendon tears with muscle fatty atrophy. PMID- 26808838 TI - Phonetic basis of phonemic paraphasias in aphasia: Evidence for cascading activation. AB - Phonemic paraphasias are a common presenting symptom in aphasia and are thought to reflect a deficit in which selecting an incorrect phonemic segment results in the clear-cut substitution of one phonemic segment for another. The current study re-examines the basis of these paraphasias. Seven left hemisphere-damaged aphasics with a range of left hemisphere lesions and clinical diagnoses including Broca's, Conduction, and Wernicke's aphasia, were asked to produce syllable initial voiced and voiceless fricative consonants, [z] and [s], in CV syllables followed by one of five vowels [i e a o u] in isolation and in a carrier phrase. Acoustic analyses were conducted focusing on two acoustic parameters signaling voicing in fricative consonants: duration and amplitude properties of the fricative noise. Results show that for all participants, regardless of clinical diagnosis or lesion site, phonemic paraphasias leave an acoustic trace of the original target in the error production. These findings challenge the view that phonemic paraphasias arise from a mis-selection of phonemic units followed by its correct implementation, as traditionally proposed. Rather, they appear to derive from a common mechanism with speech errors reflecting the co-activation of a target and competitor resulting in speech output that has some phonetic properties of both segments. PMID- 26808839 TI - Water First Aid Is Beneficial In Humans Post-Burn: Evidence from a Bi-National Cohort Study. AB - INTRODUCTION: Reported first aid application, frequency and practices around the world vary greatly. Based primarily on animal and observational studies, first aid after a burn injury is considered to be integral in reducing scar and infection, and the need for surgery. The current recommendation for optimum first aid after burn is water cooling for 20 minutes within three hours. However, compliance with this guideline is reported as poor to moderate at best and evidence exists to suggest that overcooling can be detrimental. This prospective cohort study of a bi-national burn patient registry examined data collected between 2009 and 2012. The aim of the study was to quantify the magnitude of effects of water cooling first aid after burn on indicators of burn severity in a large human cohort. METHOD: The data for the analysis was provided by the Burn Registry of Australia and New Zealand (BRANZ). The application of first aid cooling prior to admission to a dedicated burn service, was analysed for its influence on four outcomes related to injury severity. The patient related outcomes were whether graft surgery occurred, and death while the health system (cost) outcomes included total hospital length of stay and admission to ICU. Robust regression analysis using bootstrapped estimation adjusted using a propensity score was used to control for confounding and to estimate the strength of association with first aid. Dose-response relationships were examined to determine associations with duration of first aid. The influence of covariates on the impact of first aid was assessed. RESULTS: Cooling was provided before Burn Centre admission for 68% of patients, with at least twenty minutes duration for 46%. The results indicated a reduction in burn injury severity associated with first aid. Patients probability for graft surgery fell by 0.070 from 0.537 (13% reduction) (p = 0.014). The probability for ICU admission fell by 0.084 from 0.175 (48% reduction) (p<0.001) and hospital length of stay (LOS) fell by 2.27 days from 12.9 days (18% reduction) (p = 0.001). All outcomes except death showed a dose-response relationship with the duration of first aid. The size of burn and age interacted with many of the relationships between first aid and outcome and these are described and discussed. DISCUSSION & CONCLUSION: This study suggests that there are significant patient and health system benefits from cooling water first aid, particularly if applied for up to 20 minutes. The results of this study estimate the effect size of post-burn first aid and confirm that efforts to promote first aid knowledge are not only warranted, but provide potential cost savings. PMID- 26808840 TI - Factors related to allergic transfusion reactions and febrile non-haemolytic transfusion reactions in children. AB - BACKGROUND AND OBJECTIVES: Allergic transfusion reactions (ATRs) and febrile non haemolytic transfusion reactions (FNHTRs) are the two major types of transfusion related adverse reactions (TRARs). Although prestorage leucocyte reduction and diversion of the first aliquot of blood (LR/D) could reduce FNHTRs and bacterial contamination in adult transfusion, ATRs are still problematic. In addition, there is little information about TRARs in paediatric population. MATERIALS AND METHODS: We conducted a single-centre retrospective analysis of all transfusions, except washing products, and TRARs for 153 months to evaluate related factors such as delivery of treatment and the characteristics of recipients. RESULTS: Most TRARs were FNHTRs and/or ATRs in children. In delivering blood products with LR/D, the frequencies of not only FNHTRs but also ATRs were significantly reduced with both platelet concentrates (PCs) and red cell concentrates (RCCs). TRARs of fresh-frozen plasma were infrequent in children. In addition, even after the introduction of LR/D, ATRs were significantly more frequent in patients with primary haematological and malignant diseases who received PCs and RCCs, older patients who received PCs and patients who received frequent RCCs. CONCLUSION: These results suggest that leucocytes or mediators from leucocytes are underlying cause of ATRs in addition to FNHTRs in children. Furthermore, particular characteristics of patients would be other risk factors for ATRs. PMID- 26808841 TI - Acute Improvement of Vertical Jump Performance After Isometric Squats Depends on Knee Angle and Vertical Jumping Ability. AB - Tsoukos, A, Bogdanis, GC, Terzis, G, and Veligekas, P. Acute improvement of vertical jump performance after isometric squats depends on knee angle and vertical jumping ability. J Strength Cond Res 30(8): 2250-2257, 2016-This study examined the acute effects of maximum isometric squats at 2 different knee angles (90 or 140 degrees ) on countermovement jump (CMJ) performance in power athletes. Fourteen national-level male track and field power athletes completed 3 main trials (2 experimental and 1 control) in a randomized and counterbalanced order 1 week apart. Countermovement jump performance was evaluated using a force-plate before and 15 seconds, 3, 6, 9, and 12 minutes after 3 sets of 3 seconds maximum isometric contractions with 1-minute rest in between, from a squat position with knee angle set at 90 or 140 degrees . Countermovement jump performance was improved compared with baseline only in the 140 degrees condition by 3.8 +/- 1.2% on the 12th minute of recovery (p = 0.027), whereas there was no change in CMJ height in the 90 degrees condition. In the control condition, there was a decrease in CMJ performance over time, reaching -3.6 +/- 1.2% (p = 0.049) after 12 minutes of recovery. To determine the possible effects of baseline jump performance on subsequent CMJ performance, subjects were divided into 2 groups ("high jumpers" and "low jumpers"). The baseline CMJ values of "high jumpers" and "low jumpers" differed significantly (CMJ: 45.1 +/- 2.2 vs. 37.1 +/- 3.9 cm, respectively, p = 0.001). Countermovement jump was increased only in the "high jumpers" group by 5.4 +/- 1.4% (p = 0.001) and 7.4 +/- 1.2% (p = 0.001) at the knee angles of 90 and 140 degrees , respectively. This improvement was larger at the 140 degrees angle (p = 0.049). Knee angle during isometric squats and vertical jumping ability are important determinants of the acute CMJ performance increase observed after a conditioning activity. PMID- 26808842 TI - Heart Rate and Energy Expenditure in Division I Field Hockey Players During Competitive Play. AB - Sell, KM and Ledesma, AB. Heart rate and energy expenditure in Division I field hockey players during competitive play. J Strength Cond Res 30(8): 2122-2128, 2016-The purpose of this study was to quantify energy expenditure and heart rate data for Division I female field hockey players during competitive play. Ten female Division I collegiate field hockey athletes (19.8 +/- 1.6 years; 166.4 +/- 6.1 cm; 58.2 +/- 5.3 kg) completed the Yo-Yo intermittent endurance test to determine maximal heart rate. One week later, all subjects wore a heart rate monitor during a series of 3 matches in an off-season competition. Average heart rate (AvHR), average percentage of maximal heart rate (AvHR%), peak exercise heart rate (PExHR), and percentage of maximal heart rate (PExHR%), time spent in each of the predetermined heart rate zones, and caloric expenditure per minute of exercise (kcalM) were determined for all players. Differences between positions (backs, midfielders, and forwards) were assessed. No significant differences in AvHR, AvHR%, PExHR, PExHR%, and %TM were observed between playing positions. The AvHR% and PExHR% for each position fell into zones 4 (77-93% HRmax) and 5 (>93% HRmax), respectively, and significantly more time was spent in zone 4 compared with zones 1, 2, 3, and 5 across all players (p <= 0.05). The kcalM reflected very heavy intensity exercise. The results of this study will contribute toward understanding the sport-specific physiological demands of women's field hockey and has specific implications for the duration and schedule of training regimens. PMID- 26808843 TI - Muscle Activation Patterns During Different Squat Techniques. AB - Slater, LV, and Hart, JM. Muscle activation patterns during different squat techniques. J Strength Cond Res 31(3): 667-676, 2017-Bilateral squats are frequently used exercises in sport performance programs. Lower extremity muscle activation may change based on knee alignment during the performance of the exercise. The purpose of this study was to compare lower extremity muscle activation patterns during different squat techniques. Twenty-eight healthy, uninjured subjects (19 women, 9 men, 21.5 +/- 3 years, 170 +/- 8.4 cm, 65.7 +/- 11.8 kg) volunteered. Electromyography (EMG) electrodes were placed on the vastus lateralis, vastus medialis, rectus femoris, biceps femoris, and the gastrocnemius of the dominant leg. Participants completed 5 squats while purposefully displacing the knee anteriorly (AP malaligned), 5 squats while purposefully displacing the knee medially (ML malaligned) and 5 squats with control alignment (control). Normalized EMG data (MVIC) were reduced to 100 points and represented as percentage of squat cycle with 50% representing peak knee flexion and 0 and 99% representing fully extended. Vastus lateralis, medialis, and rectus femoris activity decreased in the medio-lateral (ML) malaligned squat compared with the control squat. In the antero-posterior (AP) malaligned squat, the vastus lateralis, medialis, and rectus femoris activity decreased during initial descent and final ascent; however, vastus lateralis and rectus femoris activation increased during initial ascent compared with the control squat. The biceps femoris and gastrocnemius displayed increased activation during both malaligned squats compared with the control squat. In conclusion, participants had altered muscle activation patterns during squats with intentional frontal and sagittal malalignment as demonstrated by changes in quadriceps, biceps femoris, and gastrocnemius activation during the squat cycle. PMID- 26808844 TI - Off-Ice Anaerobic Power Does Not Predict On-Ice Repeated Shift Performance in Hockey. AB - Peterson, BJ, Fitzgerald, JS, Dietz, CC, Ziegler, KS, Baker, SE, and Snyder, EM. Off-ice anaerobic power does not predict on-ice repeated shift performance in hockey. J Strength Cond Res 30(9): 2375-2381, 2016-Anaerobic power is a significant predictor of acceleration and top speed in team sport athletes. Historically, these findings have been applied to ice hockey although recent research has brought their validity for this sport into question. As ice hockey emphasizes the ability to repeatedly produce power, single bout anaerobic power tests should be examined to determine their ability to predict on-ice performance. We tested whether conventional off-ice anaerobic power tests could predict on-ice acceleration, top speed, and repeated shift performance. Forty five hockey players, aged 18-24 years, completed anthropometric, off-ice, and on ice tests. Anthropometric and off-ice testing included height, weight, body composition, vertical jump, and Wingate tests. On-ice testing consisted of acceleration, top speed, and repeated shift fatigue tests. Vertical jump (VJ) (r = -0.42; r = -0.58), Wingate relative peak power (WRPP) (r = -0.32; r = -0.43), and relative mean power (WRMP) (r = -0.34; r = -0.48) were significantly correlated (p <= 0.05) to on-ice acceleration and top speed, respectively. Conversely, none of the off-ice tests correlated with on-ice repeated shift performance, as measured by first gate, second gate, or total course fatigue; VJ (r = 0.06; r = 0.13; r = 0.09), WRPP (r = 0.06; r = 0.14; r = 0.10), or WRMP (r = -0.10; r = -0.01; r = -0.01). Although conventional off-ice anaerobic power tests predict single bout on-ice acceleration and top speed, they neither predict the repeated shift ability of the player, nor are good markers for performance in ice hockey. PMID- 26808845 TI - Similarities and Differences in Pacing Patterns in a 161-km and 101-km Ultra Distance Road Race. AB - Tan, PLS, Tan, FHY, and Bosch, AN. Similarities and differences in pacing patterns in a 161-km and 101-km ultra-distance road race. J Strength Cond Res 30(8): 2145-2155, 2016-The purpose of this study was to establish and compare the pacing patterns of fast and slow finishers in a tropical ultra-marathon. Data were collected from the Craze Ultra-marathon held on the 22nd and 21st of September in 2012 and 2013, respectively. Finishers of the 161-km (N = 47) and 101-km (N = 120) categories of the race were divided into thirds (groups A-C) by merit of finishing time. Altogether, 17 and 11 split times were recorded for the 161-km and 101-km finishers, respectively, and used to calculate the mean running speed for each distance segment. Running speed for the first segment was normalized to 100, with all subsequent splits adjusted accordingly. Running speed during the last 5 km was calculated against the mean race pace to establish the existence of an end spurt. A reverse J-shaped pacing profile was demonstrated in all groups for both distance categories and only 38% of the finishers executed an end spurt. In the 101-km category, in comparison with groups B and C, group A maintained a significantly more even pace (p = 0.013 and 0.001, respectively) and completed the race at a significantly higher percent of initial starting speed (p = 0.001 and 0.001, respectively). Descriptive data also revealed that the top 5 finishers displayed a "herd-behavior" by staying close to the lead runner in the initial portion of the race. These findings demonstrate that to achieve a more even pace, recreational ultra-runners should adopt a patient sustainable starting speed, with less competitive runners setting realistic performance goals whereas competitive runners with a specific time goal to consider running in packs of similar pace. PMID- 26808846 TI - Physiological Demands of Competitive Sprint and Distance Performance in Elite Female Cross-Country Skiing. AB - Carlsson, M, Carlsson, T, Wedholm, L, Nilsson, M, Malm, C, and Tonkonogi, M. Physiological demands of competitive sprint and distance performance in elite female cross-country skiing. J Strength Cond Res 30(8): 2138-2144, 2016-The purpose was to investigate the relationship between elite females' competitive performance capability in sprint and distance cross-country skiing and the variables of gross efficiency (GE), work rate at the onset of blood-lactate accumulation (OBLA4mmol), maximal oxygen uptake (V[Combining Dot Above]O2max), maximal speed (Vmax), and peak upper-body oxygen uptake (V[Combining Dot Above]O2peak). Ten elite female cross-country skiers (age 24.5 +/- 2.8 years) completed treadmill roller-skiing tests to determine GE, OBLA4mmol, and V[Combining Dot Above]O2max using the diagonal-stride technique as well as Vmax and V[Combining Dot Above]O2peak using the double-poling technique. International Ski Federations ranking points for sprint (FISsprint) and distance (FISdist) races were used as competitive performance data. There were correlations between the FISsprint and the V[Combining Dot Above]O2max expressed absolutely (p = 0.0040), Vmax (p = 0.012), and V[Combining Dot Above]O2peak expressed absolutely (p < 0.001) and as a simple ratio-standard (p = 0.049). The FISdist were correlated with OBLA4mmol (p = 0.048), V[Combining Dot Above]O2max expressed absolutely (L.min) (p = 0.015) and as a simple ratio-standard (p = 0.046), and V[Combining Dot Above]O2peak expressed absolutely (p = 0.036) and as a simple ratio-standard (ml.min.kg) (p = 0.040). The results demonstrate that the physiological abilities reflected by V[Combining Dot Above]O2max and V[Combining Dot Above]O2peak are indicators of competitive sprint and distance performance in elite female cross-country skiing. In addition, the ability to generate a high Vmax indicates the performance in sprint races, whereas the skier's OBLA4mmol reflects the performance capability in distance races. Based on the results, when evaluating the performance capacity of elite female cross-country skiers, it is recommended to use physiological variables that reflect competitive performance. PMID- 26808847 TI - Barefoot Running Reduces the Submaximal Oxygen Cost in Female Distance Runners. AB - Berrones, AJ, Kurti, SP, Kilsdonk, KM, Cortez, DJ, Melo, FF, and Whitehurst, M. Barefoot running reduces the submaximal oxygen cost in female distance runners. J Strength Cond Res 30(8): 2348-2353, 2016-Being a competitive distance runner is, in part, attributable to a high V[Combining Dot Above]O2max. However, running economy (RE) is a more robust indicator of distance running performance among endurance athletes of similar V[Combining Dot Above]O2max levels. The purpose of this study was to examine the influence of unshod (barefoot) vs. shod (wearing shoes) running on RE (expressed as ml.kg.min) during three 5-minute submaximal running trials representing 65, 75, and 85% of V[Combining Dot Above]O2max. Other physiologic and perceptual variables such as respiratory exchange ratio, lactate, heart rate, and ratings of perceived exertion were also chosen as dependent variables. We measured V[Combining Dot Above]O2max in 14 recreationally active trained distance female runners (age = 27.6 +/- 1.6 years; height = 163.3 +/- 1.7 cm; weight = 57.8 +/- 1.9 kg) who were completely inexperienced with unshod running. After initial testing, each subject was randomized to either unshod or shod for days 2 and 3. We analyzed the data with a 2-way (condition by intensity) repeated-measures analysis of variance. Submaximal oxygen consumption was significantly reduced at 85% of V[Combining Dot Above]O2max (p = 0.018), indicating an improvement in RE, but not during the 65% or 75% trials (p > 0.05, both). No other dependent measure was different between unshod and shod conditions. Our results indicate that the immediate improvement to RE while barefoot occurs at a relatively high fraction of maximal oxygen consumption. For the recreational or competitive distance runner, training or competing while barefoot may be a useful strategy to improve endurance performance. PMID- 26808848 TI - Acute Citrulline-Malate Supplementation and High-Intensity Cycling Performance. AB - Cunniffe, B, Papageorgiou, M, O'Brien, B, Davies, NA, Grimble, GK, and Cardinale, M. Acute citrulline-malate supplementation and high-intensity cycling performance. J Strength Cond Res 30(9): 2638-2647, 2016-Dietary L-citrulline malate (CM) consumption has been suggested to improve skeletal muscle metabolism and contractile efficiency, which would be expected to predispose exercising individuals to greater fatigue resistance. The purpose of this study was to examine the effects of CM supplementation on acid-base balance and high-intensity exercise performance. In a double-blind, placebo-controlled, crossover study, 10 well-trained males consumed either 12 g of CM (in 400 ml) or lemon sugar-free cordial (placebo [PL]) 60 minutes before completion of 2 exercise trials. Each trial consisted of subjects performing 10 (*15 seconds) maximal cycle sprints (with 30-second rest intervals) followed by 5 minutes recovery before completing a cycle time-to-exhaustion test (TTE) at 100% of individual peak power (PP). Significant increases in plasma concentrations of citrulline (8.8-fold), ornithine (3.9-fold), and glutamine (1.3-fold) were observed 60 minutes after supplementation in the CM trial only (p <= 0.05) and none of the subjects experienced gastrointestinal side-effects during testing. Significantly higher exercise heart rates were observed in CM condition (vs. PL) although no between trial differences in performance related variables (TTE: [120 +/- 61 seconds CM vs. 113 +/- 50 seconds PL]), PP or mean power, ([power fatigue index: 36 +/- 16% CM vs. 28 +/- 18% PL]), subjective rating of perceived exertion or measures of acid-base balance (pH, lactate, bicarbonate, base-excess) were observed (p > 0.05). This study demonstrated that acute supplementation of 12 g CM does not provide acute ergogenic benefits using the protocol implemented in this study in well-trained males. PMID- 26808849 TI - Physical Characteristics Underpinning Lunging and Change of Direction Speed in Fencing. AB - Turner, A, Bishop, C, Chavda, S, Edwards, M, Brazier, J, Kilduff, LP. Physical characteristics underpinning lunging and change of direction speed in fencing. J Strength Cond Res 30(8): 2235-2241, 2016-Lunge velocity (LV) and change of direction speed (CODS) are considered fundamental to success during fencing competitions; investigating the physical characteristics that underpin these is the aim of this study. Seventy fencers from the British Fencing National Academy took part and on average (+/-SD) were 16.83 +/- 1.72 years of age, 178.13 +/- 8.91 cm tall, 68.20 +/- 9.64 kg in mass, and had 6.25 +/- 2.23 years fencing experience. The relationship between anthropometric characteristics (height, arm span, and adductor flexibility) and measures of lower-body power (bilateral and unilateral countermovement jump height and reactive strength index) were examined in their ability to influence LV and CODS. In testing the former, fencers lunged (over a self-selected distance) to and from a force plate, where front leg impact and rear leg propulsive force were quantified; the lunging distance was divided by time to establish LV. Change of direction speed was measured over 12 m involving shuttles of between 2 and 4 m. Results revealed that LV and CODS averaged at 3.35 m.s and 5.45 seconds, respectively, and in both cases, standing broad jump was the strongest predictor (r = 0.51 and -0.65, respectively) of performance. Rear leg drive and front leg impact force averaged at 14.61 N.kg and 3 times body weight, respectively, with single leg jumps revealing an asymmetry favoring the front leg of 9 +/- 8%. In conclusion, fencers should train lower body power emphasizing horizontal displacement, noting that this seems to offset any advantage one would expect fencers of a taller stature to have. Also, the commonly reported asymmetry between legs is apparent from adolescence and thus also requires some attention. PMID- 26808850 TI - Metabolic Demand and Internal Training Load in Technical-Tactical Training Sessions of Professional Futsal Players. AB - Wilke, CF, Ramos, GP, Pacheco, DAS, Santos, WHM, Diniz, MSL, Goncalves, GGP, Marins, JCB, Wanner, SP, and Silami-Garcia, E. Metabolic demand and internal training load in technical-tactical training sessions of professional futsal players. J Strength Cond Res 30(8): 2330-2340, 2016-The aim of the study was to characterize aspects of technical-tactical training sessions of a professional futsal team. We addressed 4 specific aims: characterize the metabolic demands and intensity of these training sessions, compare the training intensity among players of different positions, compare the intensity of different futsal specific activities (4 * 4, 6 * 4, and match simulation), and investigate the association between an objective (training impulse; TRIMP) and a subjective method (session rating of perceived exertion; sRPE) of measuring a player's internal training load. Twelve top-level futsal players performed an incremental exercise to determine their maximal oxygen consumption, maximal heart rate (HRmax), ventilatory threshold (VT), and respiratory compensation point (RCP). Each player's HR and RPE were measured and used to calculate energy expenditure, TRIMP, and sRPE during 37 training sessions over 8 weeks. The average intensity was 74 +/- 4% of HRmax, which corresponded to 9.3 kcal.min. The players trained at intensities above the RCP, between the RCP and VT and below the VT for 20 +/- 8%, 28 +/- 6%, and 51 +/- 10% of the session duration, respectively. Wingers, defenders, and pivots exercised at a similar average intensity but with different intensity distributions. No difference in intensity was found between the 3 typical activities. A strong correlation between the average daily TRIMP and sRPE was observed; however, this relationship was significant for only 4 of 12 players, indicating that sRPE is a useful tool for monitoring training loads but that it should be interpreted for each player individually rather than collectively. PMID- 26808851 TI - Technical and Physical Activities of Small-Sided Games in Young Korean Soccer Players. AB - Joo, CH, Hwang-Bo, K, and Jee, H. Technical and physical activities of small sided games in young Korean soccer players. J Strength Cond Res 30(8): 2164-2173, 2016-The aim of this study was to examine the technical aspects and physical demands during small-sided games (SSGs) with different sized pitches in young Korean soccer players. Participants were randomly selected during a nationally held youth competition. Three different game formats were used: SSG8 (8 vs. 8 played on a small-sized field [68 * 47 m]), RSG8 (8 vs. 8 played on a regular sized field [75 * 47 m]), and RSG11 (11 vs. 11 played on a regular-sized field). Eleven technical (ball touches, passes, and shots) and 6 physical demand variables (exercise frequency by intensity) were observed and analyzed. Same variables were also analyzed for the goalkeepers. As a result, SSG8 and RSG8 showed significantly greater numbers of technical plays in 5 and 4 variables in comparison to RSG11, respectively. In addition, although the exercise intensities increased slightly in both SSG formats, the amount was within the similar range as previous reports. In conclusion, the SSGs with reduced number of players may be referred in young players to effectively train them in technical aspects of the game by allowing greater ball exposure time without excessive physical demands. Various confounding factors such as pitch dimension should be carefully considered for training specific technical and physical variables in young Korean players. PMID- 26808852 TI - Interval Running Training Improves Cognitive Flexibility and Aerobic Power of Young Healthy Adults. AB - Venckunas, T, Snieckus, A, Trinkunas, E, Baranauskiene, N, Solianik, R, Juodsnukis, A, Streckis, V, and Kamandulis, S. Interval running training improves cognitive flexibility and aerobic power of young healthy adults. J Strength Cond Res 30(8): 2114-2121, 2016-The benefits of regular physical exercise may well extend beyond the reduction of chronic diseases risk and augmentation of working capacity, to many other aspects of human well-being, including improved cognitive functioning. Although the effects of moderate intensity continuous training on cognitive performance are relatively well studied, the benefits of interval training have not been investigated in this respect so far. The aim of the current study was to assess whether 7 weeks of interval running training is effective at improving both aerobic fitness and cognitive performance. For this purpose, 8 young dinghy sailors (6 boys and 2 girls) completed the interval running program with 200 m and 2,000 m running performance, cycling maximal oxygen uptake, and cognitive function was measured before and after the intervention. The control group consisted of healthy age-matched subjects (8 boys and 2 girls) who continued their active lifestyle and were tested in the same way as the experimental group, but did not complete any regular training. In the experimental group, 200 m and 2,000 m running performance and cycling maximal oxygen uptake increased together with improved results on cognitive flexibility tasks. No changes in the results of short-term and working memory tasks were observed in the experimental group, and no changes in any of the measured indices were evident in the controls. In conclusion, 7 weeks of interval running training improved running performance and cycling aerobic power, and were sufficient to improve the ability to adjust behavior to changing demands in young active individuals. PMID- 26808853 TI - Changes in Contributions of Swimming, Cycling, and Running Performances on Overall Triathlon Performance Over a 26-Year Period. AB - Figueiredo, P, Marques, EA, and Lepers, R. Changes in contributions of swimming, cycling, and running performances on overall triathlon performance over a 26-year period. J Strength Cond Res 30(9): 2406-2415, 2016-This study examined the changes in the individual contribution of each discipline to the overall performance of Olympic and Ironman distance triathlons among men and women. Between 1989 and 2014, overall performances and their component disciplines (swimming, cycling and running) were analyzed from the top 50 overall male and female finishers. Regression analyses determined that for the Olympic distance, the split times in swimming and running decreased over the years (r = 0.25-0.43, p <= 0.05), whereas the cycling split and total time remained unchanged (p > 0.05), for both sexes. For the Ironman distance, the cycling and running splits and the total time decreased (r = 0.19-0.88, p <= 0.05), whereas swimming time remained stable, for both men and women. The average contribution of the swimming stage (~18%) was smaller than the cycling and running stages (p <= 0.05), for both distances and both sexes. Running (~47%) and then cycling (~36%) had the greatest contribution to overall performance for the Olympic distance (~47%), whereas for the Ironman distance, cycling and running presented similar contributions (~40%, p > 0.05). Across the years, in the Olympic distance, swimming contribution significantly decreased for women and men (r = 0.51 and 0.68, p < 0.001, respectively), whereas running increased for men (r = 0.33, p = 0.014). In the Ironman distance, swimming and cycling contributions changed in an undulating fashion, being inverse between the two segments, for both sexes (p < 0.01), whereas running contribution decreased for men only (r = 0.61, p = 0.001). These findings highlight that strategies to improve running performance should be the main focus on the preparation to compete in the Olympic distance; whereas, in the Ironman, both cycling and running are decisive and should be well developed. PMID- 26808854 TI - Motion Analysis of Match Play in New Zealand U13 to U15 Age-Group Soccer Players. AB - Atan, SA, Foskett, A, and Ali, A. Motion analysis of match play in New Zealand U13 to U15 age-group soccer players. J Strength Cond Res 30(9): 2416-2423, 2016 The purpose of this study was to investigate motion analysis in 85 players (U13 U15 years) from Auckland's Metropolitan League during 2 competitive soccer matches. Five-Hz global positioning system (with interpolated 10-Hz output) units were used to measure total distance (absolute and relative) and time spent in standing, walking, low-intensity running, medium-intensity running, high intensity running, and sprinting. Speed thresholds for each match activity were determined through mean 10-m flying sprint peak speed for each age group. Under 15 years (U15, 6600 +/- 1480 m) covered more absolute distance because of longer playing time than under 14 years (U14, 5385 +/- 1296 m, p = 0.001) and under 13 years (U13, 4516 +/- 702.6 m, p = 0.001). However, there were no differences in relative distances covered (U15, 94.5 +/- 11.2 m.min, U14, 96.1 +/- 11.9 m.min, U15, 97.3 +/- 17.6 m.min, p = 0.685). Maximum speed attained during the match was faster for U15 (26.5 +/- 1.68 km.h) than U14 (25.4 +/- 1.93 km.h, p = 0.022) and U13 (23.5 +/- 1.74 km.h, p = 0.001); there were no differences in average distance per sprint, with all age groups covering ~16 m per sprint (p = 0.603). The current findings provide useful information for developing specific training programs for young soccer players and a framework for developing age-specific soccer simulation protocols. PMID- 26808855 TI - Functional Movement Screening Performance of Brazilian Jiu-Jitsu Athletes From Brazil: Differences Considering Practice Time and Combat Style. AB - Boscolo Del Vecchio, F, Foster, D, and Arruda, A. Functional movement screening performance of Brazilian jiu-jitsu athletes from Brazil: differences considering practice time and combat style. J Strength Cond Res 30(8): 2341-2347, 2016 Brazilian jiu-jitsu (BJJ) is a grappling combat sport that athletes, lying (guard fighter) or kneeling (pass fighter) on the mat, attempt to force their opponents to submit. Brazilian jiu-jitsu practices may result in muscular imbalances, which increase the risk of injury. Instead, the Functional Movement Screen (FMS) is an evaluation routine that could be related to injury incidence and seeks to detect muscular imbalance and movement dysfunction. Thus, the aim of the study was to investigate the injury profile and the FMS score and their relationship, with consideration for the BJJ fight style. Sports injuries were recorded in the last 12 months of 33 BJJ athletes, and the statistical analyses were applied to a routine evaluation FMS and a score of 14 points or less was considered low performance in FMS. We used a logistic regression; the effect size (ES) was calculated, and 5% was assumed as the statistical significance level. Pass fighters showed a higher percentage of injuries on the thorax (24.24%) than did guard fighters (6.67%, p = 0.01). Upper limbs were the most injured part of the body (chi = 36.7; p < 0.001), and they were 79% of the injuries that occurred in training sessions (chi = 14.53; p < 0.001). Despite the lack of statistical differences in the FMS performance between guard and pass fighters (t = 1.97; p = 0.05), its magnitude was considered medium (ES = 0.77). There was an association between FMS and presence of injury (chi = 4.95; p = 0.03). Considering the FMS score as a predictor and the presence or absence of injury as the dependent variable, the data met a Wald coefficient of 4.55, p = 0.03 and Exp (B) = 5.71. The study found that almost half of the sample had injuries in the upper limbs and a quarter had injuries in the lower limbs in the last year. A poor FMS score was observed, and lower scores in the FMS were associated with a higher risk of injury in BJJ athletes. PMID- 26808856 TI - Caffeine Attenuates Decreases in Leg Power Without Increased Muscle Damage. AB - Ribeiro, BG, Morales, AP, Sampaio-Jorge, F, Barth, T, de Oliveira, MBC, Coelho, GMdO, and Leite, TC. Caffeine attenuates decreases in leg power without increased muscle damage. J Strength Cond Res 30(8): 2354-2360, 2016-Caffeine ingestion has been shown to be an effective ergogenic aid in several sports. Caffeine administration may increase exercise capacity, which could lead to a greater degree of muscle damage after exercise. This was a randomized, double-blind, placebo-controlled crossover study. Six male handball athletes ingested placebo (PLA) or caffeine (CAF) (6 mg.kg body mass) capsules on 2 different occasions. Sixty minutes after ingestion of the capsules, serum CAF levels were evaluated. Thereafter, all participants performed a protocol of vertical jumps (VJs). The protocol consisted of 4 sets of 30 seconds of continuous VJs with 60 seconds of recovery between sets. Blood lactate (LAC) and creatine kinase (CK) levels were determined before and after the protocol. We found significant differences in serum CAF levels between PLA (0.09 +/- 0.18 ug.ml) vs. CAF (6.59 +/- 4.44 ug.ml) (p < 0.001). Caffeine elicited a 5.23% (p <= 0.05) improvement in the leg power compared with PLA. The CAF trial displayed higher LAC (p <= 0.05) compared with PLA (6.26 +/- 2.01 vs. 4.39 +/- 2.42 mmol.L, respectively) after protocol of VJs, whereas no difference in CK was observed between trials (p > 0.05). These results indicate that immediate ingestion of CAF (6 mg.kg body weight) can reduce the level of muscle fatigue and preserve leg power during the test, possibly resulting in increase in LAC. There was no increase in muscle damage, which indicates that immediate administration of (6 mg.kg body weight) CAF is safe. Thus, nutritional interventions with CAF could help athletes withstand a greater physiological overload during high-intensity training sessions. The results of this study would be applicable to sports and activities that require repetitive leg power. PMID- 26808857 TI - Autoregulating Jump Performance to Induce Functional Overreaching. AB - Claudino, JG, Cronin, JB, Mezencio, B, Pinho, JP, Pereira, C, Mochizuki, L, Amadio, AC, and Serrao, JC. Autoregulating jump performance to induce functional overreaching. J Strength Cond Res 30(8): 2242-2249, 2016-The purpose of this study was to determine whether autoregulating jump performance using the minimal individual difference (MID) associated with countermovement jump (CMJ) height could be used to regulate and monitor a training phase that elicited functional overreaching and tapering in team sport athletes. The participants were familiarized with the jump and then the CMJ height reliability was quantified to determine the MID. Countermovement jump height was assessed in the pretesting session (T0), at the end of 4 weeks of intensified training (T1), and after 2 weeks of tapering (T2). Eighteen national level U17 male futsal players were randomly allocated into the regulated group (RG; n = 9) and the control group (CG; n = 9). The RG performed 6 weeks of training with the training load regulated by mean height of CMJ with MID, whereas the CG performed the preplanned training. The differences between groups and across time points were compared by a 2-way analysis of variance. In the RG, the MID loading was increased in weeks 3 and 4 (8.2 and 14.5%, respectively; p < 0.001) compared with the preplanned loading of the CG during the overreaching phase. In the jump results, the RG significantly (p <= 0.05) reduced CMJ height during T1 (effect size [ES] = -0.31; 95% confidence interval [CI]: -0.58 to -0.02); however, there were no significant changes in the CG jump height at T1 and T2. At T2, the RG significantly increased CMJ height above baseline (ES = 0.30; 95% CI: 0.09 to 0.51). Researchers and practitioners could use this autoregulating method to regulate and monitor training load to achieve functional overreaching in youth futsal players. PMID- 26808858 TI - Movement Profiles, Match Events, and Performance in Australian Football. AB - Johnston, RJ, Watsford, ML, Austin, D, Pine, MJ, and Spurrs, RW. Movement profiles, match events, and performance in Australian football. J Strength Cond Res 30(8): 2129-2137, 2016-This study examined the relationship between movement demands, match events, and match performance in professional Australian football. Data were collected from 19 players using global positioning system units during 2 Australian Football League seasons. A range of movement demands and instantaneous power measures were collected. The players were divided into high caliber (HC, >=17/20) and low-caliber (LC, <=8/20) groups based on the rating score by their coaches. A Mann-Whitney U-test, independent samples t-test, and effect sizes were used to determine whether any differences existed between the 2 groups. The HC group had a significantly higher match duration (7.2%), higher total distance (9.6%), and covered more distance and spent more time high-speed running per minute (12.7 and 11.9%). Although not significant, the effect sizes revealed that the HC group tended to have a higher mean metabolic power output (2.6%) and spent more time at the high power zone (7.9%). For the match event data, the HC group had significantly more involvements with the football. The results demonstrated the higher physical demands placed on the HC group. The findings suggest that analyzing instantaneous power measures can provide valuable information about the physical demands placed on team sport athletes to coaches and conditioning staff. PMID- 26808859 TI - Relationship Between Agility Tests and Short Sprints: Reliability and Smallest Worthwhile Difference in National Collegiate Athletic Association Division-I Football Players. AB - The Pro-Agility test (I-Test) and 3-cone drill (3-CD) are widely used in football to assess quickness in change of direction. Likewise, the 10-yard (yd) sprint, a test of sprint acceleration, is gaining popularity for testing physical competency in football players. Despite their frequent use, little information exists on the relationship between agility and sprint tests as well the reliability and degree of change necessary to indicate meaningful improvement resulting from training. The purpose of this study was to determine the reliability and smallest worthwhile difference (SWD) of the I-Test and 3-CD and the relationship of sprint acceleration to their performance. Division-I football players (n = 64, age = 20.5 +/- 1.2 years, height = 185.2 +/- 6.1 cm, body mass = 107.8 +/- 20.7 kg) performed duplicate trials in each test during 2 separate weeks at the conclusion of a winter conditioning period. The better time of the 2 trials for each week was used for comparison. The 10-yd sprint was timed electronically, whereas the I-Test and 3-CD were hand timed by experienced testers. Each trial was performed on an indoor synthetic turf, with players wearing multicleated turf shoes. There was no significant difference (p > 0.06) between test weeks for the I-Test (4.53 +/- 0.35 vs. 4.54 +/- 0.31 seconds), 3-CD (7.45 +/- 0.06 vs. 7.49 +/- 0.06 seconds), or 10-yd sprint (1.85 +/- 0.12 vs. 1.84 +/- 0.12 seconds). The intraclass correlation coefficients (ICC) for 3-CD (ICC = 0.962) and 10-yd sprint (ICC = 0.974) were slightly higher than for the I Test (ICC = 0.914). These values lead to acceptable levels of the coefficient of variation for each test (1.2, 1.2, and 1.9%, respectively). The SWD% indicated that a meaningful improvement due to training would require players to decrease their times by 6.6% for I-Test, 3.7% for 3-CD, and 3.8% for 10-yd sprint. Performance in agility and short sprint tests are highly related and reliable in college football players, providing quantifiable parameters for judging true change in performance as opposed to random measurement variation in college football players. PMID- 26808860 TI - Effect of Vitamin D Supplementation on Training Adaptation in Well-Trained Soccer Players. AB - Jastrzebska, M, Kaczmarczyk, M, and Jastrzebski, Z. Effect of vitamin D supplementation on training adaptation in well-trained soccer players. J Strength Cond Res 30(9): 2648-2655, 2016-There is growing body of evidence implying that vitamin D may be associated with athletic performance, however, studies examining the effects of vitamin D on athletic performance are inconsistent. Moreover, very little literature exists about the vitamin D and training efficiency or adaptation, especially in high-level, well-trained athletes. The purpose of the current study was to investigate the effect of vitamin D supplementation on training adaptation in well-trained football players. The subjects were divided into 2 groups: the placebo group (PG) and the experimental group (SG, supplemented with vitamin D, 5,000 IU per day). Both groups were subjected to High Intensity Interval Training Program. The selection to the groups was based on peak power results attained before the experiment and position on the field. Blood samples for vitamin D level were taken from the players. In addition, total work, 5, 10, 20, and 30 m running speed, squat jump, and countermovement jump height were determined. There were no significant differences between SG and PG groups for any power-related characteristics at baseline. All power-related variables, except the 30 m sprint running time, improved significantly in response to interval training. However, the mean change scores (the differences between posttraining and pretraining values) did not differ significantly between SG and PG groups. In conclusion, an 8-week vitamin D supplementation in highly trained football players was not beneficial in terms of response to High Intensity Interval Training. Given the current level of evidence, the recommendation to use vitamin D supplements in all athletes to improve performance or training gains would be premature. To avoid a seasonal decrease in 25(OH)D level or to obtain optimal vitamin D levels, the combination of higher dietary intake and vitamin D supplementation may be necessary. PMID- 26808861 TI - Comparison of Two Types of Warm-Up Upon Repeated-Sprint Performance in Experienced Soccer Players. AB - van den Tillaar, R and von Heimburg, E. Comparison of two types of warm-up upon repeated-sprint performance in experienced soccer players. J Strength Cond Res 30(8): 2258-2265, 2016-The aim of the study was to compare the effects of a long warm-up and a short warm-up upon repeated-sprint performance in soccer players. Ten male soccer players (age, 21.9 +/- 1.9 years; body mass, 77.7 +/- 8.3 kg; body height, 1.85 +/- 0.03 m) conducted 2 types of warm-ups with 1 week in between: a long warm-up (20 minutes: LWup) and a short warm-up (10 minutes: SWup). Each warm-up was followed by a repeated-sprint test consisting of 8 * 30 m sprints with a new start every 30th second. The best sprint time, total sprinting time, and % decrease in time together with heart rate, lactate, and rate of perceived exertion (RPE) were measured. No significant differences in performance were found for the repeated-sprint test parameters (total sprint time: 35.99 +/- 1.32 seconds [LWup] and 36.12 +/- 0.96 seconds [SWup]; best sprint time: 4.32 +/- 0.13 seconds [LWup] and 4.30 +/- 0.10 seconds [SWup]; and % sprint decrease: 4.16 +/- 2.15% [LWup] and 5.02 +/- 2.07% [SWup]). No differences in lactate concentration after the warm-up and after the repeated-sprint test were found. However, RPE and heart rate were significantly higher after the long warm-up and the repeated-sprint test compared with the short warm-up. It was concluded that a short warm-up is as effective as a long warm-up for repeated sprints in soccer. Therefore, in regular training, less warm-up time is needed; the extra time could be used for important soccer skill training. PMID- 26808862 TI - Passive Recovery Promotes Superior Performance and Reduced Physiological Stress Across Different Phases of Short-Distance Repeated Sprints. AB - Scanlan, AT and Madueno, MC. Passive recovery promotes superior performance and reduced physiological stress across different phases of short-distance repeated sprints. J Strength Cond Res 30(9): 2540-2549, 2016-Limited research has examined the influence of recovery modalities on run-based repeated-sprint (RS) performance with no data available relative to the sprint phase. This study compared run-based RS performance across various sprint phases and underlying physiological responses between active and passive recoveries. Nine students (21.8 +/- 3.6 years; 171.3 +/- 6.4 cm; 72.8 +/- 12.2 kg) completed 2 bouts (active and passive recoveries) of 10 * 20 m sprints interspersed with 30 s recoveries in a randomized crossover fashion. Sprint times and decrements were calculated for each split (0-5, 5-15, 15-20, and 0-20 m) across each sprint. Blood lactate concentration ([BLa]), heart rate (HR), and rating of perceived exertion (RPE) were measured at various time-points. Passive recovery promoted improved performance times (p <= 0.005) and decrements (p <= 0.045) across all splits, and lower post-test [BLa] (p <= 0.005), HR (bout 3 onwards) (p <= 0.014), and RPE (bout 4 onwards) when compared with active recovery. Performance differences between recoveries were less pronounced across the 0-5 m split. Temporal analyses showed significant (p <= 0.05) increases in sprint times and decrements primarily with active recovery. The present data indicate that passive recovery promoted superior performance across run-based RS, with earlier performance deterioration and greater physiological load evident during active recovery. These findings can aid the manipulation of interbout activity across RS drills to promote physiological overload and adaptation during training. Further, coaches may develop tactical strategies to overcome the detrimental effects of active recovery and optimize sprint performance in athletes during game-play. PMID- 26808863 TI - Synthesis and characterization of Nd2O3 nanoparticles in a radiofrequency thermal plasma reactor. AB - The synthesis of nanocrystalline Nd2O3 through an inductively coupled radiofrequency thermal plasma route is reported. Unlike in conventional synthesis processes, plasma-synthesized nanoparticles are directly obtained in a stable hexagonal crystal structure with a faceted morphology. The synthesized nanoparticles are highly uniform with an average size around 20 nm. The nanoparticles are characterized in terms of phase formation, crystallinity, morphology, size distribution, nature of chemical bonds and post-synthesis environmental effects using standard characterization techniques. X-ray diffraction, transmission electron microscopy, and scanning electron microscopy are used for structural and morphological studies. The thermo-gravimetric technique, using a differential scanning calorimeter, is used to investigate the purity of phase. Fourier transform infrared spectroscopy is used to investigate the nature of existing bonds. The optical response of the nanoparticles is investigated through the electronic transition of Nd(3+) ions in its crystalline structure via UV-visible spectroscopy. The presence of defect states and corresponding activation energies in the nanocrystalline Nd2O3 compared to those of the precursors are studied using thermoluminescence. PMID- 26808864 TI - Authorized manufacturing changes for therapeutic monoclonal antibodies (mAbs) in European Public Assessment Report (EPAR) documents. AB - Background The quality of biologicals, including biosimilars, is subject to change as a result of manufacturing process modifications following initial authorization. It is important that such product changes have no adverse impact on product efficacy or safety, including immunogenicity. Objectives The aim of this study was to investigate the number and types of manufacturing changes for originator mAbs (the reference for the comparability exercise to confirm biosimilarity) according to European Public Assessment Report (EPAR) documentation and to ascertain the level of risk these changes might impart. The extensive body of evidence contained in the EPAR documents can help support the EMA during the EC marketing authorization approval process for biosimilars, since it provides a broad base of scientific experience. Research designs and methods For EPAR-listed mAbs, details of all changes listed chronologically in the EPAR were evaluated and described. Based on these descriptions the manufacturing changes can be categorized by risk status (low, moderate or high). Results Entries for 29 mAbs with publicly available EPAR reports were reviewed. These contained details of 404 manufacturing changes authorized by the European Medicines Agency (EMA): 22 were categorized as high risk, 286 as moderate risk and 96 as low risk manufacturing changes. A limitation of this analysis is that it only summarizes publicly available data from EPAR documents. Conclusions Manufacturing change data indicate that the EMA has significant experience of process changes for originator mAbs, and the impact they may have on the efficacy and safety of biologicals. This experience will be useful in biosimilar product development to ensure adherence to sound scientific principles. Compared with the established manufacturing process for a reference product, the production of biosimilars will usually be different. Consequently, in addition to a comprehensive comparative functional and physicochemical characterization analysis, clinical data is required to confirm mAb biosimilarity. PMID- 26808866 TI - A Rational Strategy for Graphene Transfer on Substrates with Rough Features. AB - Graphene grown by chemical vapor deposition is transferred by a very simple, yet effective approach from the growth substrate onto substrates with rough features. This novel and facile method not only results in satisfactory transfer on substrates with terraces or grooves, but also gives rise to a successful result for uneven growth substrates. PMID- 26808865 TI - Ingestion of Milk Containing Very Low Concentration of Antimicrobials: Longitudinal Effect on Fecal Microbiota Composition in Preweaned Calves. AB - Although antimicrobial drugs are central to combat disease in modern medicine, the use of these drugs can have undesired consequences for human and animal health. One consequence is the post-therapy excretion of pharmacological agents, such as the elimination of drug residues at very low concentrations in the milk of lactating mammals. Limited information is currently available on the impact from the exposure of the gut microbiota to drug residues using in vivo natural models. The objective of our study was to address this knowledge gap and evaluate the effect on the fecal microbiota composition from feeding preweaned dairy calves raw milk with residual concentrations of ampicillin, ceftiofur, penicillin, and oxytetracycline from birth to weaning. At birth, thirty calves were randomly assigned to a controlled feeding trial where: 15 calves were fed raw milk with no drug residues (NR), and 15 calves were fed raw milk with drug residues (DR) by adding ceftiofur, penicillin, ampicillin, and oxytetracycline at final concentrations in the milk of 0.1, 0.005, 0.01, and 0.3 MUg/ml, respectively. Fecal samples were rectally collected from each calf once a week starting at birth, prior to the first feeding in the trial (pre-treatment), until 6 weeks of age. Sequencing of the microbial 16S rRNA genes was conducted using the Illumina MiSeq, which provides a high resolution of the microbiota down to the genus level. Discriminant analysis showed that, except for pre-treatment samples, calves fed milk with drug residues and calves fed milk without drug residues easily discriminated at the genus level on their weekly microbial profile. However, analysis comparing the abundance of taxon between NR and DR showed significant differences only at the genus levels, and not at the phylum, class, order or family levels. These results suggest that although drug residues can result in clear discriminate gut microbial communities, they do not result in disruption of taxonomic levels above the genus. PMID- 26808867 TI - Role of Purinergic Receptor Expression and Function for Reduced Responsiveness to Adenosine Diphosphate in Washed Human Platelets. AB - BACKGROUND: Washing of platelets is an important procedure commonly used for experimental studies, e.g. in cardiovascular research. As a known phenomenon, responsiveness to adenosine diphosphate (ADP) is reduced in washed platelets, although underlying molecular mechanisms-potentially interfering with experimental results-have not been thoroughly studied. OBJECTIVES: Since ADP mediates its effects via three purinergic receptors P2Y1, P2X1 and P2Y12, their surface expression and function were investigated in washed platelets and, for comparison, in platelet-rich-plasma (PRP) at different time points for up to 2 hours after preparation. RESULTS: In contrast to PRP, flow cytometric analysis of surface expression in washed platelets revealed an increase of all receptors during the first 60 minutes after preparation followed by a significant reduction, which points to an initial preactivation of platelets and consecutive degeneration. The activity of the P2X1 receptor (measured by selectively induced calcium flux) was substantially maintained in both PRP and washed platelets. P2Y12 function (determined by flow cytometry as platelet reactivity index) was partially reduced after platelet washing compared to PRP, but remained stable in course of ongoing storage. However, the function of the P2Y1 receptor (measured by selectively induced calcium flux) continuously declined after preparation of washed platelets. CONCLUSION: In conclusion, decreasing ADP responsiveness in washed platelets is particularly caused by impaired activity of the P2Y1 receptor associated with disturbed calcium regulation, which has to be considered in the design of experimental studies addressing ADP mediated platelet function. PMID- 26808868 TI - Performance assessment of biofuel production in an algae-based remediation system. AB - The production of biofuel from microalgae has been an area of great interest as microalgae have higher productivities than land plants, and certain species have high lipid constituents which are the major feedstock for biodiesel production. One way to enhance the economic feasibility of algal-based biofuel is to couple it with waste remediation. This study investigated the technical feasibility of cultivating Chlorella sp. and Nannochloropsis sp. with fish water for biofuel production. The remediation potential of Chlorella sp. was found to be higher but the lipid yield is lower, when compared to Nannochloropsis sp. Lipid productivities were found to be similar for both types of algae at 1.1-1.3mgL( 1)h(-1). The fatty acid profiles of the obtained lipids were found suitable for biofuel production, and the calorific values were high at 30-32MJ/kg. The results provide insights into lipid production in Chlorella sp. and Nannochloropsis sp., when coupled with waste remediation. PMID- 26808869 TI - Complete genome sequence of the xylan-degrading subseafloor bacterium Microcella alkaliphila JAM-AC0309. AB - Here we report the complete genome sequence of Microcella alkaliphila JAM-AC0309, which was newly isolated from the deep subseafloor core sediment from offshore of the Shimokita Peninsula of Japan. An array of genes related to utilization of xylan in this bacterium was identified by whole genome analysis. PMID- 26808870 TI - Complete genome of Planococcus rifietoensis M8(T), a halotolerant and potentially plant growth promoting bacterium. AB - Planococcus rifietoensis M8(T) (=DSM 15069(T)=ATCC BAA-790(T)) is a halotolerant bacterium with potential plant growth promoting properties isolated from an algal mat collected from a sulfurous spring in Campania (Italy). This paper presents the first complete genome of P. rifietoensis M8(T). Genes coding for various potentially plant growth promoting properties were identified within its genome. PMID- 26808871 TI - Complete genome sequence of the Aneurinibacillus soli CB4(T) from soil of mountain. AB - Aneurinibacillus soli CB4(T) is a Gram-positive, motile rods and strictly aerobic bacterium. Here we present the 4.1-Mb genome sequence of the type strain of A. soli CB4(T), which consists a chromosome for the total 4,116,770bp with a G+C content of 45.9mol%. Genes related to diverse secondary metabolites were detected in this genome. The genomic data is expected to understand the possibility of industrial and commercial use by strain CB4(T). PMID- 26808872 TI - Conjugative transfer of broad host range plasmids to an acidobacterial strain, Edaphobacter aggregans. AB - The Acidobacteria phylum is of high ecological interest. Its members are ubiquitous and particularly abundant in soils but many are recalcitrant to cultivation in the laboratory. Thus, the ability of Acidobacteria to capture and maintain plasmids remains largely unexplored. In this work we tested the transfer and the stability of (i) the PromA plasmid pMOL98 and (ii) the IncQ plasmid pKT230 to the acidobacterial strain Edaphobacter aggregans DSM 19364. To this end quantitative conjugation assays were performed and transconjugants were scored for plasmid-borne antibiotic selection markers. The tested plasmids were transferred and maintained in the new host. Plasmid pMOL98 was more stable than pKT230 in Ed. aggregans in the absence of positive selection. Thus, from an ecological point of view, we have extended the host range of PromA and IncQ plasmids for the first time to an acidobacterial strain. Furthermore, we have uncovered the potential of Acidobacteria to capture as-yet-unknown plasmids and to foster the development of new cloning and expression systems for the exploitation of biotechnologically valuable soil resources. PMID- 26808873 TI - 2015 Health Physics Society Symposium, 13-14 July 2015, Health Risks From Low Doses and Low Dose-Rates of Ionizing Radiation. PMID- 26808874 TI - Is Ionizing Radiation Harmful at any Exposure? An Echo That Continues to Vibrate. AB - The health risks to humans and non-human biota exposed to low dose ionizing radiation remain ambiguous and are the subject of intense debate. The need to establish risk assessment standards based on the mechanisms underlying low-level radiation exposure has been recognized by regulatory agencies as critical to adequately protect people and to make the most effective use of national resources. Here, the authors briefly review evidence showing that the molecular and biochemical changes induced by low doses of radiation differ from those induced by high doses. In particular, an array of redundant and inter-related mechanisms act in both prokaryotes and eukaryotes to restore DNA integrity following exposures to relatively low doses of sparsely ionizing radiation. Furthermore, the radiation-induced protective mechanisms often overcompensate and minimize the mutagenic potential of the byproducts of normal oxidative metabolism. In contrast to adaptive protection observed at low doses of sparsely ionizing radiation, there is evidence that even a single nuclear traversal by a densely ionizing particle track can trigger harmful effects that spread beyond the traversed cell and induce damaging effects in the nearby bystander cells. In vivo studies examining whether exposure to low dose radiation at younger age modulates the latency of expression of age-related diseases such as cancer, together with studies on the role of genetic susceptibility, will further illuminate the magnitude of risk of exposure to low dose radiation. PMID- 26808875 TI - Physical Considerations. AB - It seems likely that the biological consequences of radiation exposure are the result of sequences of biochemical processes initiated by the chemical changes caused by energy deposited as ionization or excitation. Based on this assumption, it would appear that a detailed knowledge of the energy deposited in relevant biological targets would provide a basis for predicting the biological risk. However, there is generally insufficient knowledge of the biological processes for such predictions to be successful. However, knowledge of energy deposition characteristics can help to determine if specific models of biological processes are tenable. Furthermore, an alternative to absorbed dose may provide a way to characterize the energy deposition, which is more easily related to the health risk and less likely to be misconstrued when used to describe low levels of radiation exposure. Some examples of limits on models and alternatives to absorbed dose are described. PMID- 26808876 TI - The Integration of LNT and Hormesis for Cancer Risk Assessment Optimizes Public Health Protection. AB - This paper proposes a new cancer risk assessment strategy and methodology that optimizes population-based responses by yielding the lowest disease/tumor incidence across the entire dose continuum. The authors argue that the optimization can be achieved by integrating two seemingly conflicting models; i.e., the linear no-threshold (LNT) and hormetic dose-response models. The integration would yield the optimized response at a risk of 10 with the LNT model. The integrative functionality of the LNT and hormetic dose response models provides an improved estimation of tumor incidence through model uncertainty analysis and major reductions in cancer incidence via hormetic model estimates. This novel approach to cancer risk assessment offers significant improvements over current risk assessment approaches by revealing a regulatory sweet spot that maximizes public health benefits while incorporating practical approaches for model validation. PMID- 26808877 TI - Health Risks From Low Doses and Low Dose-Rates of Ionizing Radiation. Session 5: Future of Radiation Protection Regulations. AB - The system of radiological protection is a prospective approach to protection of individuals in all exposure situations. It must be applied equitably across all age groups and all populations. This is a very different circumstance from dose assessment for a particular individual where the unique characteristics of the individual and the exposure can be taken into account. Notwithstanding the ongoing discussions on the possible shape of the dose response at low doses and dose rates, the prospective system of protection has therefore historically used a linear assumption as a pragmatic, prudent and protective approach. These radiation protection criteria are not intended to be a demarcation between "safe" and "unsafe" and are the product of a risk-informed judgement that includes inputs from science, ethics, and experience. There are significant implications for different dose response relationships. A linear model allows for equal treatment of an exposure, irrespective of the previously accumulated exposure. In contrast, other models would predict different implications. Great care is therefore needed in separating the thinking around risk assessment from risk management, and prospective protection for all age groups and genders from retrospective assessment for a particular individual. In the United States, the prospective regulatory structure functions effectively because of assumptions that facilitate independent treatment of different types of exposures, and which provide pragmatic and prudent protection. While the a linear assumption may, in fact, not be consistent with the biological reality, the implications of a different regulatory model must be considered carefully. PMID- 26808878 TI - Space Radiation Quality Factors and the Delta Ray Dose and Dose-Rate Reduction Effectiveness Factor. AB - In this paper, the authors recommend that the dose and dose-rate effectiveness factor used for space radiation risk assessments should be based on a comparison of the biological effects of energetic electrons produced along a cosmic ray particles path in low fluence exposures to high dose-rate gamma-ray exposures of doses of about 1 Gy. Methods to implement this approach are described. PMID- 26808879 TI - Urgent Change Needed to Radiation Protection Policy. AB - Although almost 120 y of medical experience and data exist on human exposure to ionizing radiation, advisory bodies and regulators claim there are still significant uncertainties about radiation health risks that require extreme precautions be taken. Decades of evidence led to recommendations in the 1920s for protecting radiologists by limiting their daily exposure. These were shown in later studies to decrease both their overall mortality and cancer mortality below those of unexposed groups. In the 1950s, without scientific evidence, the National Academy of Sciences Biological Effects of Atomic Radiation (BEAR) Committee and the NCRP recommended that the linear no-threshold (LNT) model be used to assess the risk of radiation-induced mutations in germ cells and the risk of cancer in somatic cells. This policy change was accepted by the regulators of every country without a thorough review of its basis. Because use of the LNT model has created extreme public fear of radiation, which impairs vital medical applications of low-dose radiation in diagnostics and therapy and blocks nuclear energy projects, it is time to change radiation protection policy back into line with the data. PMID- 26808880 TI - Inferences, Risk Modeling, and Prediction of Health Effects of Ionizing Radiation. AB - The combined expertise of radiation epidemiologists and laboratory experimentalists is required to accurately define health risks from exposure to a low/very low radiation dose. Although stochastic risk can be estimated when a known threshold dose is exceeded, risk must be inferred from data transference at sub-threshold doses. The clinician's dilemma is evident when complying with accepted medical practice that is complicated by potential long-term, adverse outcomes. By contrast, radiation protection regulators must make prudent judgments without complete knowledge of the scope and consequences of their actions. Only by combining the strengths of epidemiological and experimental laboratory approaches can accurate predictive modeling be achieved after exposure to a low/very low dose. PMID- 26808881 TI - Future of Radiation Protection Regulations. AB - THERE IS considerable disagreement in the scientific community regarding the carcinogenicity of low-dose radiation (LDR), with publications supporting opposing points of view. However, major flaws have been identified in many of the publications claiming increased cancer risk from LDR. The data generally recognized as the most important for assessing radiation effects in humans, the atomic bomb survivor data, are often cited to raise LDR cancer concerns. However, these data no longer support the linear no-threshold (LNT) model after the 2012 update but are consistent with radiation hormesis. Thus, a resolution of the controversy regarding the carcinogenicity of LDR appears to be imminent, with the rejection of the LNT model and acceptance of radiation hormesis. Hence, for setting radiation protection regulations, an alternative approach to the present one based on the LNT model is needed. One approach would be to determine the threshold dose for the carcinogenic effect of radiation from existing data and establish regulations to ensure radiation doses are kept well below the threshold dose. This can be done by setting dose guidelines specifying safe levels of radiation doses, with the requirement that these safe levels, referred to as guidance levels, not be exceeded significantly. Using this approach, a dose guidance level of 10 cGy for acute radiation exposures and 10 cGy y for exposures over extended periods of time are recommended. The concept of keeping doses as low as reasonably achievable, known as ALARA, would no longer be required for low level radiation exposures not expected to exceed the dose guidance levels significantly. These regulations would facilitate studies using LDR for prevention and treatment of diseases. Results from such studies would be helpful in refining dose guidance levels. The dose guidance levels would be the same for the public and radiation workers to ensure everyone's safety. PMID- 26808882 TI - Quantification of Adaptive Protection Following Low-dose Irradiation. AB - The question whether low doses and low dose-rates of ionizing radiation pose a health risk to people is of public, scientific and regulatory concern. It is a subject of intense debate and causes much fear. The controversy is to what extent low-dose effects, if any, cause or protect against damage such as cancer. Even if immediate molecular damage in exposed biological systems rises linearly with the number of energy deposition events (i.e., with absorbed dose), the response of the whole biological system to that damage is not linear. To understand how initial molecular damage affects a complex living system is the current challenge. PMID- 26808883 TI - Response of Biological Systems to Low Doses of Ionizing Radiation. AB - Radiation is ubiquitous in the environment. Biological effects of exposure to low doses of ionizing radiation are subjected to several modulating factors. Two of these, bystander response and adaptive protections, are discussed briefly. PMID- 26808884 TI - Physical Considerations for Understanding Responses of Biological Systems to Low Doses of Ionizing Radiation: Nucleosome Clutches Constitute a Heterogeneous Distribution of Target Volumes. AB - Humans are exposed to low doses of ionizing radiation that arise from a variety of sources. The response of biological systems to low doses of ionizing radiation depend on many factors. Some of the physical factors include distribution of the radiation sources, radiation track structure, structure and dimensions of the biological targets, temporal patterns of radiation exposure(s), absorbed dose rate and total absorbed dose. Recent discoveries suggest that assumptions regarding the structure of an important biological target, namely chromatin, may not be correct. It is now believed that chromatin fiber consists of heterogeneous groups of nucleosomes called clutches, and the distribution of clutch sizes differs between somatic cells and stem cells. This shift in paradigm may have implications for radiation target theory and its explanation of observations of clustered DNA damage. PMID- 26808885 TI - To Scan or not to Scan: Consideration of Medical Benefit in the Justification of CT Scanning. AB - While there are ongoing debates with regard to the level of risk, if any, associated with medical imaging, the benefits from medical imaging exams are well documented. This forum article looks at outcome-based medical studies and guidance from expert panels in an effort to bring the benefits of medical imaging, specifically CT imaging, into focus. The position is taken that imaging, medical, and safety communities must not continue to discuss small hypothetical risks from ionizing radiation without emphasizing the large well-documented benefits from medical imaging exams that use ionizing radiation. PMID- 26808886 TI - Compelling Issues Compounding the Understanding of Low Dose Radiation Effects: But Do They Matter? AB - Recent advances in low dose radiation research have raised a number of compelling issues that have compounded the understanding of low dose radiation effects. Here some of them are outlined: the linear no-threshold model for predicting effects at low radiation doses, dose rate effectiveness factor, attributability, and public perception of low dose radiation effects. The impact of changes in any of these hotly debated issues on radiation protection is considered. PMID- 26808887 TI - Health Benefits of Exposure to Low-dose Radiation. AB - Although there is no doubt that exposure to high doses of radiation (delivered at a high dose-rate) induces harmful effects, the health risks and benefits of exposure to low levels (delivered at a low dose-rate) of toxic agents is still a challenging public health issue. There has been a considerable amount of published data against the linear no-threshold (LNT) model for assessing risk of cancers induced by radiation. The LNT model for risk assessment creates "radiophobia," which is a serious public health issue. It is now time to move forward to a paradigm shift in health risk assessment of low-dose exposure by taking the differences between responses to low and high doses into consideration. Moreover, future research directed toward the identification of mechanisms associated with responses to low-dose radiation is critically needed to fully understand their beneficial effects. PMID- 26808888 TI - Magnification of Inter-individual Variation in Biological Responses After Low Doses and Dose-Rates of Ionizing Radiation. AB - Biological responses of human cells and tissues to ionizing radiation (IR) are strongly influenced by dose and dose-rate. Unlike the robust activation of cellular DNA damage responses (DDR) seen after high IR doses, the efficiency of activation of DNA damage repair and signaling pathways after much lower doses and dose-rates varies appreciably among different individuals. Genomic and functional assays measuring low dose and dose-rate IR responses repeatedly show increased inter-individual variability when cells and tissues experience DNA damage levels comparable to those experienced endogenously (due to aerobic metabolism, diet, lifestyle, etc). Complicating matters for risk assessment are recent observations of dose-response non-linearity (hyper-linearity) in the low dose range. With both physical and biological factors strongly influencing individual responses to IR at low doses and dose-rates, further radiobiological research is required to assist regulatory agencies in determining appropriate radiological protection standards for such exposures. PMID- 26808889 TI - Low Dose Effects: Benefit or Harm? AB - This forum article discusses issues related to the effects of low dose radiation, an area that is under intense study but difficult to assess. Experiments with large-scale animal studies are included in this paper; these studies point to the need for international consortia to examine and balance the results of these large-scale studies and databases. PMID- 26808890 TI - The Neglected Side of the Coin: Quantitative Benefit-risk Analyses in Medical Imaging. AB - While it is implicitly recognized that the benefits of diagnostic imaging far outweigh any theoretical radiogenic risks, quantitative estimates of the benefits are rarely, if ever, juxtaposed with quantitative estimates of risk. This alone - expression of benefit in purely qualitative terms versus expression of risk in quantitative, and therefore seemingly more certain, terms - may well contribute to a skewed sense of the relative benefits and risks of diagnostic imaging among healthcare providers as well as patients. The current paper, therefore, briefly compares the benefits of diagnostic imaging in several cases, based on actual mortality or morbidity data if ionizing radiation were not employed, with theoretical estimates of radiogenic cancer mortality based on the "linear no threshold" (LNT) dose-response model. PMID- 26808894 TI - Combining the Complete Active Space Self-Consistent Field Method and the Full Configuration Interaction Quantum Monte Carlo within a Super-CI Framework, with Application to Challenging Metal-Porphyrins. AB - A novel stochastic Complete Active Space Self-Consistent Field (CASSCF) method has been developed and implemented in the Molcas software package. A two-step procedure is used, in which the CAS configuration interaction secular equations are solved stochastically with the Full Configuration Interaction Quantum Monte Carlo (FCIQMC) approach, while orbital rotations are performed using an approximated form of the Super-CI method. This new method does not suffer from the strong combinatorial limitations of standard MCSCF implementations using direct schemes and can handle active spaces well in excess of those accessible to traditional CASSCF approaches. The density matrix formulation of the Super-CI method makes this step independent of the size of the CI expansion, depending exclusively on one- and two-body density matrices with indices restricted to the relatively small number of active orbitals. No sigma vectors need to be stored in memory for the FCIQMC eigensolver--a substantial gain in comparison to implementations using the Davidson method, which require three or more vectors of the size of the CI expansion. Further, no orbital Hessian is computed, circumventing limitations on basis set expansions. Like the parent FCIQMC method, the present technique is scalable on massively parallel architectures. We present in this report the method and its application to the free-base porphyrin, Mg(II) porphyrin, and Fe(II) porphyrin. In the present study, active spaces up to 32 electrons and 29 orbitals in orbital expansions containing up to 916 contracted functions are treated with modest computational resources. Results are quite promising even without accounting for the correlation outside the active space. The systems here presented clearly demonstrate that large CASSCF calculations are possible via FCIQMC-CASSCF without limitations on basis set size. PMID- 26808895 TI - A Geographic Analysis about the Spatiotemporal Pattern of Breast Cancer in Hangzhou from 2008 to 2012. AB - BACKGROUND: Breast cancer (BC) is the most common female malignant tumor. Previous studies have suggested a big incidence disparity among different cities in China. The present work selected a typical city, Hangzhou, to study BC incidence disparity within the city. METHODS: Totally, 8784 female breast cancer cases were obtained from the Hangzhou Center for Disease Control and Prevention during the period 2008-2012. Analysis of Variance and Poisson Regression were the statistical tools implemented to compare incidence disparity in the space-time domain (reference group: township residents during 2008, area: subdistrict, town, and township, time frame: 2008-2012), space-time scan statistics was employed to detect significant spatiotemporal clusters of BC compared to the null hypothesis that the probability of cases diagnosed at a particular location was equal to the probability of cases diagnosed in the whole study area. Geographical Information System (GIS) was used to generate BC spatial distribution and cluster maps at the township level. RESULTS: The subdistrict populations were found to have the highest and most stable BC incidence. Although town and township populations had a relatively low incidence, it displayed a significant increasing trend from 2008 to 2012. The BC incidence distribution was spatially heterogeneous and clustered with a trend-surface from the southwest low area to the northeast high area. High clusters were located in the northeastern Hangzhou area, whereas low clusters were observed in the southwestern area during the time considered. CONCLUSIONS: Better healthcare service and lifestyle changes may be responsible for the increasing BC incidence observed in towns and townships. One high incidence cluster (Linping subdistrict) and two low incidence clusters (middle Hangzhou) were detected. The low clusters may be attributable mainly to developmental level disparity, whereas the high cluster could be associated with other risk factors, such as environmental pollution. PMID- 26808896 TI - Robot-like dexterity without computers and motors: a review of hand-held laparoscopic instruments with wrist-like tip articulation. AB - INTRODUCTION: Conventional manual laparoscopic instruments for minimally invasive surgery have limited dexterity within the patient, making procedures challenging. Surgical robotic systems offer enhanced articulation, but at substantial financial costs. This has motivated the development of high-dexterity, low-cost laparoscopic instruments. AREAS COVERED: This article reviews both commercial and academic results on creating fully mechanical (i.e. non-robotic) laparoscopic instruments that provide wrists or wrist-like dexterity within the patient. We review the state of the art in the development of these mechanical instruments, focusing on the surgeon interface, wrist mechanism, and the kinematic mapping between the two. Expert commentary: Current articulated mechanical laparoscopic instruments exhibit a wide range of designs, with no clear consensus on what makes such devices easy to use. As these technologies mature, user studies are needed to determine surgeon preferences. Articulated, low-cost instruments have the potential to impact the minimally invasive surgery market if they provide compelling benefits to surgeons. PMID- 26808897 TI - Chronic post-thyroidectomy pain: Incidence, typology, and risk factors. AB - Chronic postoperative pain exists in varying degrees for every type of surgery. An evaluation of the incidence, the typology and predictive factors of chronic pain was carried out at 3 and 6months after thyroidectomy. A prospective observational study, having included each of the patients prior to their thyroidectomy, was carried out over 12months. The patients used an 11-point numerical rating scale (NRS), a neuropathic pain screening questionnaire (DN4), an evaluation scale for anxiety and for the need for information related to anaesthesia and surgery (APAIS), a questionnaire describing pain (QDSA) and a questionnaire evaluating neuropathic pain (NPSI) before surgery and at three and six months later. Three hundred and four patients were included. The questionnaires were completed by 251 patients (57 males and 194 females) at 3 and 6months (82%). At 3months, 31 out of 251 (12%) patients mentioned a DN4>=3; at 6months, this rate dropped to 23 out of 251 (9%). The average intensity of chronic postoperative pain remained low to moderate. Levels of anxiety and the need for information were higher in patients with postoperative pain at 3 and 6months. In contrast, the number of intraoperative procedures using a bilateral superficial cervical plexus block (BSCPB) was lower in patients with DN4>=3. Multivariate analysis demonstrated that the type of anaesthesia procedure interfered with the risk of delayed pain after thyroidectomy. The presence of a DN4>=3 was nearly three-fold greater in patients without BSCPB (OR 2.647, CI=1.198-5.848). PMID- 26808899 TI - Structural disorder of monomeric alpha-synuclein persists in mammalian cells. AB - Intracellular aggregation of the human amyloid protein alpha-synuclein is causally linked to Parkinson's disease. While the isolated protein is intrinsically disordered, its native structure in mammalian cells is not known. Here we use nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy to derive atomic-resolution insights into the structure and dynamics of alpha-synuclein in different mammalian cell types. We show that the disordered nature of monomeric alpha-synuclein is stably preserved in non neuronal and neuronal cells. Under physiological cell conditions, alpha-synuclein is amino-terminally acetylated and adopts conformations that are more compact than when in buffer, with residues of the aggregation-prone non-amyloid-beta component (NAC) region shielded from exposure to the cytoplasm, which presumably counteracts spontaneous aggregation. These results establish that different types of crowded intracellular environments do not inherently promote alpha-synuclein oligomerization and, more generally, that intrinsic structural disorder is sustainable in mammalian cells. PMID- 26808898 TI - Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2. AB - Methyl-CpG binding protein 2 (MeCP2) has crucial roles in transcriptional regulation and microRNA processing. Mutations in the MECP2 gene are found in 90% of patients with Rett syndrome, a severe developmental disorder with autistic phenotypes. Duplications of MECP2-containing genomic segments cause the MECP2 duplication syndrome, which shares core symptoms with autism spectrum disorders. Although Mecp2-null mice recapitulate most developmental and behavioural defects seen in patients with Rett syndrome, it has been difficult to identify autism like behaviours in the mouse model of MeCP2 overexpression. Here we report that lentivirus-based transgenic cynomolgus monkeys (Macaca fascicularis) expressing human MeCP2 in the brain exhibit autism-like behaviours and show germline transmission of the transgene. Expression of the MECP2 transgene was confirmed by western blotting and immunostaining of brain tissues of transgenic monkeys. Genomic integration sites of the transgenes were characterized by a deep sequencing-based method. As compared to wild-type monkeys, MECP2 transgenic monkeys exhibited a higher frequency of repetitive circular locomotion and increased stress responses, as measured by the threat-related anxiety and defensive test. The transgenic monkeys showed less interaction with wild-type monkeys within the same group, and also a reduced interaction time when paired with other transgenic monkeys in social interaction tests. The cognitive functions of the transgenic monkeys were largely normal in the Wisconsin general test apparatus, although some showed signs of stereotypic cognitive behaviours. Notably, we succeeded in generating five F1 offspring of MECP2 transgenic monkeys by intracytoplasmic sperm injection with sperm from one F0 transgenic monkey, showing germline transmission and Mendelian segregation of several MECP2 transgenes in the F1 progeny. Moreover, F1 transgenic monkeys also showed reduced social interactions when tested in pairs, as compared to wild-type monkeys of similar age. Together, these results indicate the feasibility and reliability of using genetically engineered non-human primates to study brain disorders. PMID- 26808900 TI - Uranium-mediated electrocatalytic dihydrogen production from water. AB - Depleted uranium is a mildly radioactive waste product that is stockpiled worldwide. The chemical reactivity of uranium complexes is well documented, including the stoichiometric activation of small molecules of biological and industrial interest such as H2O, CO2, CO, or N2 (refs 1 - 11), but catalytic transformations with actinides remain underexplored in comparison to transition metal catalysis. For reduction of water to H2, complexes of low-valent uranium show the highest potential, but are known to react violently and uncontrollably forming stable bridging oxo or uranyl species. As a result, only a few oxidations of uranium with water have been reported so far; all stoichiometric. Catalytic H2 production, however, requires the reductive recovery of the catalyst via a challenging cleavage of the uranium-bound oxygen-containing ligand. Here we report the electrocatalytic water reduction observed with a trisaryloxide U(III) complex [(((Ad,Me)ArO)3mes)U] (refs 18 and 19)--the first homogeneous uranium catalyst for H2 production from H2O. The catalytic cycle involves rare terminal U(IV)-OH and U(V)=O complexes, which have been isolated, characterized, and proven to be integral parts of the catalytic mechanism. The recognition of uranium compounds as potentially useful catalysts suggests new applications for such light actinides. The development of uranium-based catalysts provides new perspectives on nuclear waste management strategies, by suggesting that mildly radioactive depleted uranium--an abundant waste product of the nuclear power industry--could be a valuable resource. PMID- 26808901 TI - Parkinson's disease: Disorder in the court. PMID- 26808902 TI - Clines with partial panmixia across a geographical barrier. AB - In geographically structured populations, partial global panmixia can be regarded as the limiting case of long-distance migration. In the presence of a geographical barrier, an exact, discrete model for the evolution of the gene frequencies at a multiallelic locus under viability selection, local adult migration, and partial panmixia is formulated. For slow evolution, from this model a spatially unidimensional continuous approximation (a system of integro partial differential equations with discontinuities at the barrier) is derived. For (i) the step-environment, (ii) homogeneous, isotropic migration on the entire line, and (iii) two alleles without dominance, an explicit solution for the unique polymorphic equilibrium is found. In most natural limiting cases, asymptotic expressions are obtained for the gene frequencies on either side of the barrier. PMID- 26808903 TI - Statistics Commentary Series: Commentary #13--Controlling for Baseline Differences. PMID- 26808904 TI - Seroprevalence of Crimean-Congo Hemorrhagic Fever Virus in Erzincan Province, Turkey, Relationship with Geographic Features and Risk Factors. AB - To determine the seroprevalence and risk factors associated with Crimean-Congo hemorrhagic fever virus (CCHFV) in residents of Erzincan, Turkey. Although CCHFV is endemic in Erzincan, this is the first study to evaluate its seroprevalence in this region. This study included a total of 372 subjects, 174 of whom had been exposed to or bitten by ticks, 145 of whom worked with livestock, and 53 of whom resided in the city and did not have exposure to livestock. Data on CCHFV IgG and IgM antibodies were extracted from serum samples collected from all subjects using an ELISA. All samples were tested for CCHFV IgG and CCHFV IgM. Only IgM positive samples were processed for detection of viral RNA through RT-PCR. Using seropositive cases only, we performed spatial analyses to evaluate correlations between seroprevalence and geographic location (i.e., proximity to rivers, altitude, and slope angle of land). In this study, 14.0% (52/322) of the total subjects were positive for CCHFV IgG. Seven of the individuals were positive both for CCHFV IgG and CCHFV IgM. Of these seven, only one sample tested positive for CCHFV RNA. Individuals who worked with livestock in the rural areas and had a history of tick exposure were statistically more likely to test positive for CCHFV IgG than individuals from the city and not exposed to ticks (p < 0.05). Seroprevalence was affected by geographic characteristics, including distance to rivers, altitude, and slope angle of land. We observed a high seroprevalence of CCHFV in Erzincan, which is similar to that observed in other endemic regions of Turkey. CCHFV seroprevalence rates are found to be quite high in the people who live in the sloping fields at certain heights and where there are a lot of rivers and streams. PMID- 26808905 TI - Metal oxide nanocluster-modified TiO2 as solar activated photocatalyst materials. AB - In this review we describe our work on new TiO2 based photocatalysts. The key concept in our work is to form new composite structures by the modification of rutile and anatase TiO2 with nanoclusters of metal oxides and our density functional theory (DFT) level simulations are validated by experimental work synthesizing and characterizing surface-modified TiO2. We use DFT to show that nanoclusters of different metal oxides, TiO2, SnO/SnO2, PbO/PbO2, NiO and CuO can be adsorbed at rutile and anatase surfaces and can induce red shifts in the absorption edge to enable visible light absorption which is the first key requirement for a practical photocatalyst. We furthermore determine the origin of the red shift and discuss the factors influencing this shift and the fate of excited electrons and holes. For p-block metal oxides we show how the oxidation state of Sn and Pb can be used to tune both the magnitude of the red shift and also its mechanism. Finally, aiming to make our models more realistic, we present some new results on the stability of water at rutile and anatase surfaces and the effect of water on oxygen vacancy formation and on nanocluster modification. These nanocluster-modified TiO2 structures form the basis of a new class of photocatalysts which will be useful in oxidation reactions and with the suitable choice of nanocluster modifier can be applied to CO2 reduction. PMID- 26808906 TI - Sialolithiasis is associated with nephrolithiasis: a case-control study. AB - CONCLUSIONS: This study demonstrates an association between sialolithiasis and nephrolithiasis. The results call for more awareness of this association among physicians and patients with nephrolithiasis. OBJECTIVE: Very few empirical studies have been conducted to explore the potential association between sialolithiasis and nephrolithiasis. As such, the association between sialolithiasis and nephrolithiasis still remains unclear. This study aimed to explore the possible association between sialolithiasis and nephrolithiasis using a population-based dataset. METHODS: Using data from the Taiwan Longitudinal Health Insurance Database 2005, this case-control study identified 966 patients with sialolithiasis as cases and 2898 sex- and age-matched subjects without sialolithiasis as controls. Conditional logistic regressions were conducted to examine the association of sialolithiasis with previously diagnosed nephrolithiasis. RESULTS: Out of 3864 sampled patients, 165 (4.27%) had prior nephrolithiasis. Using Chi-square test, it was found that there was a significant difference in the prevalence of prior nephrolithiasis between the cases and controls (10.25% vs 2.28%, p < 0.001). Moreover, by conditional logistic regression analysis, the odds ratio of prior nephrolithiasis for cases was 4.74 (95% CI = 3.41-6.58, p < 0.001) when compared to controls after adjusting for monthly income, geographic location, urbanization level of residence, diabetes, hypertension, heart failure, chronic renal disease, and tobacco use. PMID- 26808908 TI - Accounting for metal bioavailability in assessing water quality: A step change? AB - Bioavailability of metals to aquatic organisms can be considered to be a combination of the physicochemical factors governing metal behavior and the specific pathophysiological characteristics of the organism's biological receptor. Effectively this means that a measure of bioavailability will reflect the exposures that organisms in the water column actually "experience". This is important because it has long been established that measures of total metal in waters have limited relevance to potential environmental risk. The concept of accounting for bioavailability in regard to deriving and implementing environmental water quality standards is not new, but the regulatory reality has lagged behind the development of scientific evidence supporting the concept. Practical and technical reasons help to explain this situation. For example, concerns remain from regulators and the regulated that the efforts required to change existing systems of metal environmental protection that have been in place for over 35 yr are so great as not to be commensurate with likely benefits. However, more regulatory jurisdictions are now considering accounting for metal bioavailability in assessments of water quality as a means to support evidence based decision-making. In the past decade, both the US Environmental Protection Agency and the European Commission have established bioavailability-based standards for metals, including Cu and Ni. These actions have shifted the debate toward identifying harmonized approaches for determining when knowledge is adequate to establish bioavailability-based approaches and how to implement them. PMID- 26808909 TI - In response: Government perspective. PMID- 26808910 TI - The challenge: Establishing policy in an uncertain world: What can be done to address emerging environmental contaminants having indeterminate or subtle ecological or human impacts? PMID- 26808911 TI - In response: Academic perspective. PMID- 26808912 TI - Corrigendum. PMID- 26808913 TI - Erratum. PMID- 26808915 TI - Limited value of transbronchial lung biopsy for diagnosing Mycobacterium avium complex lung disease. AB - BACKGROUND AND AIMS: It remains unclear whether transbronchial lung biopsy (TBLB) is useful for diagnosing Mycobacterium avium complex (MAC) lung disease. METHODS: Thirty-eight consecutive patients with MAC lung disease, who were evaluated with TBLB tissue culture between June 2006 and May 2010, were included. Bronchial washing (BW) and histopathological evaluation were performed in all patients. The positivity rates of BW and TBLB tissue culture, and typical histopathological findings for MAC disease were investigated. Furthermore, all patients were divided into two groups according to the presence of intrabronchial purulent or mucopurulent secretion and the clinical, bacteriological and pathological characteristics were compared between the two groups. RESULTS: The positive culture rates of BW and TBLB specimens for MAC were 100% (38 patients) and 28.9% (11 patients). BW materials were much more sensitive for culture positivity than TBLB specimens (P < 0.0001). Typical pathological findings for MAC disease were present in the TBLB specimens of only 11 patients (28.9%). Intrabronchial secretion was identified in 15 patients (39.5%, secretion-positive group) and absent in 23 patients (60.5%, secretion-negative group). Typical histopathological findings for MAC disease were more common in the secretion positive group than in the secretion-negative group (53.3% vs 13.0%, P = 0.01), although the radiological classification and smear positivity of BW were not different between the two groups. CONCLUSION: TBLB for pathological and bacterial investigations would provide only a limited value for MAC diagnosis. Moreover, the presence of intrabronchial secretion may be an important manifestation of ongoing airway damage, which would require early treatment. PMID- 26808916 TI - Vibsane-type diterpenes from leaves and twigs of Viburnum odoratissimum. AB - Seven new vibsane-type diterpenes, vibsanols C-H (1-6) and vibsanin X (7), together with seven analogues, were isolated from the leaves and twigs of Viburnum odoratissimum. The structures of the new compounds were elucidated by extensive spectroscopic methods. All the new compounds were detected for their cytotoxicity. Compound 1 showed significant cytotoxicity against all the tested cell lines (HL-60, SMMC-7721, A-594, MCF-7, and SW-480), with IC50 values of 3.35, 4.41, 5.18, 11.30, and 3.70 MUM, respectively. Compounds 4 and 5 also displayed significant cytotoxicity against hepatocellular carcinoma SMMC-7721 cell line, with IC50 values of 3.69 and 3.52 MUM, respectively. PMID- 26808918 TI - CD73-adenosine: a next-generation target in immuno-oncology. AB - Cancer immunotherapy has entered in a new era with the development of first generation immune checkpoint inhibitors targeting the PD1/PD-L1 and CTLA-4 pathways. In this context, considerable research effort is being deployed to find the next generation of cancer immunotherapeutics. The CD73-adenosine axis constitutes one of the most promising pathways in immuno-oncology. We and others have demonstrated the immunosuppressive role of CD73-adenosine in cancer and established proof-of-concept that the targeted blockade of CD73 or adenosine receptors could effectively promote anti-tumor immunity and enhance the activity of first-generation immune checkpoint blockers. With Phase I clinical trials now underway evaluating anti-CD73 or anti-A2A therapies in cancer patients, we here discuss the fundamental, preclinical and clinical findings related to the role of the CD73-adenosinergic pathway in tumor immunity. PMID- 26808919 TI - The role of geochemistry and energetics in the evolution of modern respiratory complexes from a proton-reducing ancestor. AB - Complex I or NADH quinone oxidoreductase (NUO) is an integral component of modern day respiratory chains and has a close evolutionary relationship with energy conserving [NiFe]-hydrogenases of anaerobic microorganisms. Specifically, in all of biology, the quinone-binding subunit of Complex I, NuoD, is most closely related to the proton-reducing, H2-evolving [NiFe]-containing catalytic subunit, MbhL, of membrane-bound hydrogenase (MBH), to the methanophenzine-reducing subunit of a methanogenic respiratory complex (FPO) and to the catalytic subunit of an archaeal respiratory complex (MBX) involved in reducing elemental sulfur (S degrees ). These complexes also pump ions and have at least 10 homologous subunits in common. As electron donors, MBH and MBX use ferredoxin (Fd), FPO uses either Fd or cofactor F420, and NUO uses either Fd or NADH. In this review, we examine the evolutionary trajectory of these oxidoreductases from a proton reducing ancestral respiratory complex (ARC). We hypothesize that the diversification of ARC to MBH, MBX, FPO and eventually NUO was driven by the larger energy yields associated with coupling Fd oxidation to the reduction of oxidants with increasing electrochemical potential, including protons, S degrees and membrane soluble organic compounds such as phenazines and quinone derivatives. Importantly, throughout Earth's history, the availability of these oxidants increased as the redox state of the atmosphere and oceans became progressively more oxidized as a result of the origin and ecological expansion of oxygenic photosynthesis. ARC-derived complexes are therefore remarkably stable respiratory systems with little diversity in core structure but whose general function appears to have co-evolved with the redox state of the biosphere. This article is part of a Special Issue entitled Respiratory Complex I, edited by Volker Zickermann and Ulrich Brandt. PMID- 26808921 TI - Controlled Vectorial Electron Transfer and Photoelectrochemical Applications of Layered Relay/Photosensitizer-Imprinted Au Nanoparticle Architectures on Electrodes. AB - Two configurations of molecularly imprinted bis-aniline-bridged Au nanoparticles (NPs) for the specific binding of the electron acceptor N,N'-dimethyl-4,4' bipyridinium (MV(2+) ) and for the photosensitizer Zn(II)-protoporphyrin IX (Zn(II)-PP-IX) are assembled on electrodes, and the photoelectrochemical features of the two configurations are discussed. Configuration I includes the MV(2+) imprinted Au NPs matrix as a base layer, on which the Zn(II)-PP-IX-imprinted Au NPs layer is deposited, while configuration II consists of a bilayer corresponding to the reversed imprinting order. Irradiation of the two electrodes in the presence of a benzoquinone/benzohydroquinone redox probe yields photocurrents of unique features: (i) Whereas configuration I yields an anodic photocurrent, the photocurrent generated by configuration II is cathodic. (ii) The photocurrents obtained upon irradiation of the imprinted electrodes are substantially higher as compared to the nonimprinted surfaces. The high photocurrents generated by the imprinted Au NPs-modified electrodes are attributed to the effective loading of the imprinted matrices with the MV(2+) and Zn(II)-PP-IX units and to the effective charge separation proceeding in the systems. The directional anodic/cathodic photocurrents are rationalized in terms of vectorial electron transfer processes dictated by the imprinting order and by the redox potentials of the photosensitizer/electron acceptor units associated with the imprinted sites in the two configurations. PMID- 26808920 TI - The Effects of Acute Dopamine Precursor Depletion on the Reinforcing Value of Exercise in Anorexia Nervosa. AB - This study investigated whether dopaminergic systems are involved in the motivation to engage in behaviours associated with anorexia nervosa (AN), specifically, the drive to exercise. Women recovered from AN (AN REC, n = 17) and healthy controls (HC, n = 15) were recruited. The acute phenylalanine/tyrosine depletion (APTD) method was used to transiently decrease dopamine synthesis and transmission. The effect of dopamine precursor depletion on drive to exercise was measured using a progressive ratio (PR) exercise breakpoint task. Both groups worked for the opportunity to exercise, and, at baseline, PR breakpoint scores were higher in AN REC than HC. Compared to values on the experimental control session, APTD did not decrease PR breakpoint scores in AN REC, but significantly decreased scores in HC. These data show that women recovered from AN are more motivated to exercise than HC, although in both groups, activity is more reinforcing than inactivity. Importantly, decreasing dopamine does not reduce the motivation to exercise in people recovered from AN, but in contrast, does so in HC. It is proposed that in AN, drive to exercise develops into a behaviour that is largely independent of dopamine mediated reward processes and becomes dependent on cortico-striatal neurocircuitry that regulates automated, habit- or compulsive-like behaviours. These data strengthen the case for the involvement of reward, learning, habit, and dopaminergic systems in the aetiology of AN. PMID- 26808917 TI - Obesity and Cancer: An Angiogenic and Inflammatory Link. AB - With the current epidemic of obesity, a large number of patients diagnosed with cancer are overweight or obese. Importantly, this excess body weight is associated with tumor progression and poor prognosis. The mechanisms for this worse outcome, however, remain poorly understood. We review here the epidemiological evidence for the association between obesity and cancer, and discuss potential mechanisms focusing on angiogenesis and inflammation. In particular, we will discuss how the dysfunctional angiogenesis and inflammation occurring in adipose tissue in obesity may promote tumor progression, resistance to chemotherapy, and targeted therapies such as anti-angiogenic and immune therapies. Better understanding of how obesity fuels tumor progression and therapy resistance is essential to improve the current standard of care and the clinical outcome of cancer patients. To this end, we will discuss how an anti diabetic drug such as metformin can overcome these adverse effects of obesity on the progression and treatment resistance of tumors. PMID- 26808922 TI - Vision-Related Quality of Life in Patients with Inactive HLA-B27-Associated Spectrum Anterior Uveitis. AB - We investigated the vision-related quality of life (VR-QOL) in patients with HLA B27 associated anterior uveitis (AU). The study was conducted in 2012 at the ophthalmology department of the University Medical Center of Groningen. We included AU patients who were HLA-B27 positive and/or were diagnosed by a rheumatologist with an HLA-B27 associated systemic disease. Sixty-one of 123 (50%) adult patients participated. All patients filled-out the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25), Beck Depression Inventory (BDI-II), social support lists and an additional questionnaire for gathering general information. Medical records were reviewed for clinical characteristics. Analyses were conducted on various patient and ocular characteristics. We compared our NEI VFQ-25 scores with those previously found in the literature. Our main outcome measures were VR-QOL scores and their associations with various general patient and ocular characteristics. We found that the NEI VFQ-25 mean overall composite score was 88.9+/-8.8, which is relatively high, but lower than that found in a normal working population. The mean general health score was 47.4+/-20.8, which is lower than in patients with other ocular diseases. Patients with a systemic disease scored significantly lower on general health and VR-QOL, compared to patients without a systemic disease. Patients with a depression (6/59 (10%)) frequently had ankylosing spondylitis (5/6 patients) and they scored significantly worse on VR-QOL. We concluded that patients with HLA-B27 associated AU have a relatively high VR-QOL. However, the presence of a systemic disease is associated with lower VR-QOL and general health scores. In addition, depression is associated with a lower VR-QOL. PMID- 26808923 TI - Cytorhabdovirus P protein suppresses RISC-mediated cleavage and RNA silencing amplification in planta. AB - Plant viruses have evolved to undermine the RNA silencing pathway by expressing suppressor protein(s) that interfere with one or more key components of this antiviral defense. Here we show that the recently identified RNA silencing suppressor (RSS) of lettuce necrotic yellows virus (LNYV), phosphoprotein P, binds to RNA silencing machinery proteins AGO1, AGO2, AGO4, RDR6 and SGS3 in protein-protein interaction assays when transiently expressed. In planta, we demonstrate that LNYV P inhibits miRNA-guided AGO1 cleavage and translational repression, and RDR6/SGS3-dependent amplification of silencing. Analysis of LNYV P deletion mutants identified a C-terminal protein domain essential for both local RNA silencing suppression and interaction with AGO1, AGO2, AGO4, RDR6 and SGS3. In contrast to other viral RSS known to disrupt AGO activity, LNYV P sequence does not contain any recognizable GW/WG or F-box motifs. This suggests that LNYV P may represent a new class of AGO binding proteins. PMID- 26808925 TI - Neuroendocrine tumors of the gastrointestinal tract and the role of cytotoxic chemotherapy. AB - Neuroendocrine tumors (NETs) comprise a heterogeneous group of tumors derived from peptide- and amine-secreting cells of the neuroendocrine system. NETs commonly arise in the gastrointestinal tract but can arise in most organs of the body. Although the incidence of NETs is not high, the prevalence is relatively high because many patients may live relatively long periods without major symptoms from the disease. Whilst many of these tumors take on an indolent clinical course, they constitute a therapeutic challenge when they progress, metastasize and become symptomatic. Treatment requires a multidisciplinary approach that may include cytotoxic chemotherapy. Almost all clinical trials investigating cytotoxic chemotherapy in NETs are small single-arm studies, hence guidelines are derived from expert opinion and from extrapolating results from small-cell lung cancer studies. This article provides a broad coverage of systemic therapies for NETs but focusses on the role of cytotoxic chemotherapy. PMID- 26808926 TI - Bioactive peptide carnosin protects against lead acetate-induced hepatotoxicity by abrogation of oxidative stress in rats. AB - Context Oxidative stress is a common mechanism of liver injury. Carnosine is a dipeptide having strong antioxidant effects. Objectives We investigated the effects of carnosine on lead-induced hepatotoxicity and oxidative stress in rats. Materials and methods Animals received an aqueous solution of lead acetate (500 mg Pb/L in the drinking water) and/or daily oral gavage of carnosine (10 mg/kg) for 8 weeks. Rats were then weighed and used for the biochemical (commercial kits), molecular (standard chemical methods) and histological (microscopic) evaluations. Results Lead-induced oxidative stress in liver tissue was indicated by a significant increase in the level of malondialdehyde (MDA) (8.25 +/- 0.15 nmol/mg) as well as decrease in the level of total antioxidant capacity (TAC) (1.72 +/- 0.25 MUmol/g) and total thiol (SH) groups) 1.9 +/- 0.22 MUmol/g). Carnosine treatment decreased MDA (4 +/- 0.08 nmol/mg), whereas it increased the contents of total thiol (3.25 +/- 0.04 MUmol/g) and TAC (3.44 +/- 0.32 MUmol/g) in the lead group. Carnosine also prevented the decreased body weight (p < 0.001), albumin (p < 0.05) and total protein levels (p < 0.001) and increased liver weight (p < 0.05) and activates of hepatic enzymes (p's < 0.001) (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase) in the lead group. Furthermore, histopathological study showed that carnosine attenuates liver damage by decreasing necrosis and infiltration of inflammatory cells. Conclusion Carnosine prevented lead-induced hepatotoxicity, indicated by molecular, biochemical and histopathological analyses through inhibiting lipid peroxidation and enhancing antioxidant defence systems. Therefore, carnosine makes a good candidate to protect against the deleterious effect of chronic lead intoxication. PMID- 26808924 TI - Borrelia burgdorferi BBK32 Inhibits the Classical Pathway by Blocking Activation of the C1 Complement Complex. AB - Pathogens that traffic in blood, lymphatics, or interstitial fluids must adopt strategies to evade innate immune defenses, notably the complement system. Through recruitment of host regulators of complement to their surface, many pathogens are able to escape complement-mediated attack. The Lyme disease spirochete, Borrelia burgdorferi, produces a number of surface proteins that bind to factor H related molecules, which function as the dominant negative regulator of the alternative pathway of complement. Relatively less is known about how B. burgdorferi evades the classical pathway of complement despite the observation that some sensu lato strains are sensitive to classical pathway activation. Here we report that the borrelial lipoprotein BBK32 potently and specifically inhibits the classical pathway by binding with high affinity to the initiating C1 complex of complement. In addition, B. burgdorferi cells that produce BBK32 on their surface bind to both C1 and C1r and a serum sensitive derivative of B. burgdorferi is protected from killing via the classical pathway in a BBK32 dependent manner. Subsequent biochemical and biophysical approaches localized the anti-complement activity of BBK32 to its globular C-terminal domain. Mechanistic studies reveal that BBK32 acts by entrapping C1 in its zymogen form by binding and inhibiting the C1 subcomponent, C1r, which serves as the initiating serine protease of the classical pathway. To our knowledge this is the first report of a spirochetal protein acting as a direct inhibitor of the classical pathway and is the only example of a biomolecule capable of specifically and noncovalently inhibiting C1/C1r. By identifying a unique mode of complement evasion this study greatly enhances our understanding of how pathogens subvert and potentially manipulate host innate immune systems. PMID- 26808927 TI - Characteristics of Low-Frequency Molecular Phonon Modes Studied by THz Spectroscopy and Solid-State ab Initio Theory: Polymorphs I and III of Diflunisal. AB - THz absorption spectra of two polymorphs of diflunisal, form I and form III, exhibit distinct features due to the influence of packing conformations on the frequency distributions and IR activities of gamma point phonon modes within the 100 cm(-1) region. In order to understand the origins of these THz modes, we perform a detailed mode analysis. The result shows that although the spectral features are different, these low-frequency phonon modes of the two molecular polymorphs have similar vibrational characteristics in terms of harmonic couplings of intermolecular and intramolecular vibrations. PMID- 26808928 TI - An autumnal reflection. PMID- 26808930 TI - Teaching learners to whistle? PMID- 26808929 TI - Looking to the future: should 'prognosis' be heard as often as 'diagnosis' in medical education? PMID- 26808931 TI - Medical education: hitting the target but missing the point. AB - There are dangers that a target-driven culture could be affecting medical education. In continuous professional development, many accreditation authorities require physicians to complete a fixed number of hours of continuous professional development per year or to acquire a certain amount of continuous professional development points per year. However, all these numbers are arbitrary and worse reinforce the message to physicians that it is time spent on learning that is important. In fact far more important than hours spent is the ability to assess learning needs, learn in the light of these needs and put learning into action. Targets have also started to come to the fore is in undergraduate and postgraduate training programmes, and in certain clinical topics such as dementia and in workforce development. Targets in any walk of life should be SMART - that is specific, measurable, achievable, realistic and time limited. However, not all targets in medical education satisfy these criteria of good-quality targets. There is also the wider question as to whether there is a good fit between medical education - which is largely a qualitative activity - and educational targets - which by their nature must be quantitative. Put simply, targets may not fit with education. PMID- 26808932 TI - International medical graduates: a qualitative exploration of factors associated with success in the clinical skills assessment. AB - BACKGROUND: International medical graduates (IMGs) are known to have significantly lower first attempt pass rates at the clinical skills assessment examination (CSA) than UK graduates. Whilst much has been published concerning higher fail rates in this group, there has been very little exploration of factors associated with success. AIMS: This research aims to identify and explore factors associated with success in the CSA. METHOD: Telephone interviews with 10 IMGs who had passed the CSA on their first attempt were undertaken. Participants were current or recent (previous academic year) GP trainees in Scotland. Transcripts of the interviews were analysed by a thematic analysis approach. RESULTS: Six main themes emerged from the data analysis. These were insights into the challenges, a proactive approach, refining consultation skills, learning with UK graduates, valuing feedback and supportive relationships. Conclucions: This research adds the much-needed voice and experience of IMGs to a current area of uncertainty and challenge in medical education. It provides some insights into potential solutions to the issues and will be of interest to both trainees and those involved in their education. PMID- 26808933 TI - Commentary (on Ragg et al.). PMID- 26808934 TI - Experiences of Irish general practice trainees who participate in 4-month rotations in Malawi and Australia. AB - BACKGROUND: International health electives provide doctors and medical students with unique educational experiences. The HSE South East GP training programme in Waterford, Ireland has run a four-month elective to Malawi since 2006, and also ran a four-month placement in Australia between 2004 and 2011. AIM: The aim of this study was to see whether these overseas electives provide Irish GP trainees with any positive or negative experiences, and to make recommendations regarding future similar rotations abroad. METHOD: This study used the Delphi survey technique, a qualitative research method. The first round questionnaire asked about challenges faced while overseas, what the trainees learned, and how the placement influenced their clinical practice on their return to Ireland. Doctors were also asked about the benefits and/or limitations of an overseas placement during GP training. RESULTS: These Irish GP trainees reported very positive outcomes from time spent in Malawi and Australia. They reported improved knowledge and skills, and increased awareness of health issues and cultural differences in another country. Moreover, they had an opportunity to reflect and grow personally as doctors. CONCLUSION: This is the first study looking at an international health elective as part of a vocational training programme in Ireland. PMID- 26808935 TI - Foundation doctors career choice and factors influencing career choice. AB - This study is seeking to establish the factors influencing foundation doctors' decision-making when applying for speciality training. A questionnaire was sent to all foundation doctors in Scotland (n = 1602, response rate 34%) asking them about their career intention in relation to General Practice, whether they received career advice and the extent to which certain factors influenced their career choice. For the majority of trainees, General Practice was not their first choice but just under half were considering it as a career. There were significant differences in career choices between the four Scottish regions and between the medical schools, with a greater proportion of those who studied in Aberdeen and Dundee Medical Schools opting for a career in General Practice. Undergraduate GP placement was reported as the strongest influence in favour of a career in General Practice followed by discussion with family and friends and discussion with speciality trainees. There were differences between medical schools in the way hospital placements, General Practice placements and role models influenced career choices. Career advice on General Practice was reported to be less available and more difficult to find. PMID- 26808936 TI - Longitudinal survey on integrative medicine education at an underserved health centre. AB - Complementary and alternative medicine (CAM) is widely used by adults in the USA. However, most physicians do not inquire about CAM use leading to missed opportunities to dialogue about wellness and detect harmful practices. In 2012, an integrative medicine (IM) consultation clinic alongside an optional IM Residency Track for family medicine residents was established at the University of California, Irvine Family Health Center in Santa Ana, CA. This study evaluated the impact of these programmes on physicians' CAM/IM knowledge and receptiveness. Online surveys assessing self-reported attitudes, knowledge and practices were distributed in 2012 (baseline) and 2014 (follow-up) to family physicians with response rates of 83% (35/42) and 62% (23/37), respectively. At baseline, 91.5% of physicians believed that patient satisfaction would moderately/strongly increase if offered CAM/IM consultations and therapies. At follow- up, physician understanding of clinical applications of massage, acupuncture, meditation/relaxation, yoga and Tai Chi increased. Percentage of physician referrals to a CAM/IM consultation clinic increased (5.7- 69.6%; p < 0.01) as well as physician-initiated CAM/IM discussion (20.0-60.9%; p < 0.01). This study demonstrates the immediate effect of IM education in a primary care training site and the receptiveness of its community-based physicians towards these changes. PMID- 26808938 TI - Apprentice leaders in training: 'talking the walk'. PMID- 26808939 TI - Sometimes less is more. PMID- 26808937 TI - Teaching multimorbidity management to GP trainees: a pilot workshop. AB - Multimorbidity, the presence of more than one chronic condition simultaneously, has a significant impact on people who experience it and on the healthcare system. General Practitioners (GPs) are ideally situated to provide the complex care required for someone whose health needs to cross the boundaries of individual specialties. It has been suggested that medical and postgraduate general practice education needs to adapt to address the new challenges of multimorbidity. We present an educational approach to the teaching of multimorbidity management in a postgraduate general practice training setting. We demonstrate that a workshop using simulated multimorbidity cases and facilitated by experienced GPs improves knowledge of and confidence in managing multimorbidity in primary care. PMID- 26808940 TI - Cognitive apprenticeship. PMID- 26808942 TI - Housekeeping revisited. PMID- 26808941 TI - The flipped classroom. PMID- 26808948 TI - Develop a Q methodological study. AB - This paper provides a brief introduction to Q methodology, a research technique which allows researchers to reveal the key subjective or 'first-person' viewpoints extant amongst a group of participants. Design and participant issues are considered and coverage is provided about the processes of Q sorting, the factor analysis of the completed Q sorts and the interpretation of any emergent factors. Useful references and websites are also provided as a means of helping the interested reader to get started with Q methodology. PMID- 26808949 TI - Flip the classroom. AB - Given the huge expansion in medical knowledge it is both practical and expedient to make better use of students' time with aids for effective learning, rather than by increasing the length of time it takes to earn a medical degree. Embracing a 'flipped classroom' approach is a way to free-up classroom time to promote active learning through opportunities such as case-based and team-based exercises. PMID- 26808950 TI - What are the CPD needs of GPs working in areas of high deprivation? Report of a focus group meeting of 'GPs at the Deep End'. PMID- 26808951 TI - Need for targeted community based teaching and training for medical students and postgraduate trainees. PMID- 26808952 TI - Do students prefer being on their own or in pairs during their GP attachment? PMID- 26808953 TI - Backgrounds and aspirations of primary care academic clinical fellows. PMID- 26808954 TI - Training the assessors: A Mini-CEX workshop for GPs who assess undergraduate medical students. PMID- 26808955 TI - Narrative and culture. PMID- 26808956 TI - A cautionary note about focus groups in medical education. PMID- 26808958 TI - Mechanochemical Encapsulation of Fullerenes in Peptidic Containers Prepared by Dynamic Chiral Self-Sorting and Self-Assembly. AB - Molecular capsules composed of amino acid or peptide derivatives connected to resorcin[4]arene scaffolds through acylhydrazone linkers have been synthesized using dynamic covalent chemistry (DCC) and hydrogen-bond-based self-assembly. The dynamic character of the linkers and the preference of the peptides towards self assembly into beta-barrel-type motifs lead to the spontaneous amplification of formation of homochiral capsules from mixtures of different substrates. The capsules have cavities of around 800 A(3) and exhibit good kinetic stability. Although they retain their dynamic character, which allows processes such as chiral self-sorting and chiral self-assembly to operate with high fidelity, guest complexation is hindered in solution. However, the quantitative complexation of even very large guests, such as fullerene C60 or C70 , is possible through the utilization of reversible covalent bonds or the application of mechanochemical methods. The NMR spectra show the influence of the chiral environment on the symmetry of the fullerene molecules, which results in the differentiation of diastereotopic carbon atoms for C70 , and the X-ray structures provide unique information on the modes of peptide-fullerene interactions. PMID- 26808959 TI - Six-Minute Walk Test in Children With Spastic Cerebral Palsy and Children Developing Typically. AB - PURPOSE: To quantify the 6-minute walk test (6MWT) in children with spastic cerebral palsy (CP) functioning at Gross Motor Function Classification System (GMFCS) levels I to III and to compare with a sample of children with typical development (TD). METHODS: A total of 145 children with CP and 137 children with TD completed the 6MWT. RESULTS: Mean 6MWT scores were 439.57 +/- 49.81 m for children functioning at GMFCS level I (n = 74), 386.74 +/- 66.47 m for GMFCS level II (n = 53), 305.28 +/- 66.95 m for GMFCS level III (n = 18), and 528.42 +/ 67.77 m for children with TD (n = 137). Results of a pair-wise comparison showed significant differences (P < .001) between 6MWT scores of children with CP across GMFCS levels I to III and children with TD. CONCLUSION: A range of 6-minute walk distance reference values for children with spastic CP and children with TD were established. PMID- 26808960 TI - Modified Constraint-Induced Movement Therapy as a Home-Based Intervention for Children With Cerebral Palsy. AB - PURPOSE: This study was designed to investigate the benefit to upper limb function of a home-based version of pediatric constraint-induced movement therapy, which was delivered across 2 months. METHODS: Nine children (mean age: 6 years, 9 months) with hemiplegic cerebral palsy participated in this A1-B-C-A2 design, where A1 and A2 were nonintervention phases. In phases B and C, participants wore a splint on the unaffected hand. In phase C, motivating feedback through a computer game was added. RESULTS: The Melbourne Assessment of Unilateral Upper Limb Function and the Quality of Upper Extremity Skills Test scores were significantly higher at the end of phases B (P = .037 and P = .006, respectively) and C (P = .001 and P = .001, respectively). Melbourne scores remained higher at the end of phase A2 (P = .001). CONCLUSIONS: A nonintensive form of home-based constraint-induced movement therapy was found to be effective. Improvements were larger after the second month of intervention. PMID- 26808961 TI - Comparison of Optical Coherence Tomography Measurement Reproducibility between Children and Adults. AB - PURPOSE: To compare the reproducibility of SD-OCT (spectral-domain optical coherence tomography) measurements of RNFL (retinal nerve fiber layer) and macular thickness between children and adults. METHODS: Seventy-one eyes of 71 children and 71 eyes of 71 adults were prospectively enrolled. RNFL and macular thicknesses were measured by one operator, with a brief rest between measurements. The two measurements were obtained using the eye tracking and retest function of Spectralis SD-OCT. Reproducibility was evaluated with reference to COVs (coefficients of variation) and ICCs (intraclass correlation coefficients). The ICC values of the RNFL and macular thicknesses were compared, respectively between the two groups, by Fisher's z-test. RESULTS: The RNFL and macular thicknesses did not differ between the two groups. The COVs of the RNFL measurements ranged from 0.945 to 4.531% in the children group and from 0.496 to 1.391% in the adults group. In most of the RNFL sectors, the ICCs of the children group (range: 0.731-0.987) were significantly lower than those of the adults group (range: 0.986-0.993). The COVs of the macular measurements ranged from 0.496 to 1.157% in the children group and from 0.275 to 0.656% in the adults group. The ICCs (range: 0.860-0.974) in the children group, significantly lower than for the adults (range: 0.989-0.995), in all of the macular sectors. CONCLUSIONS: The reproducibility of SD-OCT RNFL and macular measurements for children was excellent, albeit statistically lower than that for adults. PMID- 26808962 TI - Whooping cough in a renal transplant recipient. AB - Whooping cough is a respiratory infection with a severity that varies with age, immune status, and probably with other factors such as the degree of exposure and the virulence of the organism. The most frequent microorganism responsible for whooping cough is Bordetella pertussis. We present the case of a 62-year-old renal transplant recipient presenting with typical and severe manifestations of whooping cough caused by B. pertussis. PMID- 26808963 TI - Prediction and Characterization of Dry-out Heat Flux in Micropillar Wick Structures. AB - Thin-film evaporation in wick structures for cooling high-performance electronic devices is attractive because it harnesses the latent heat of vaporization and does not require external pumping. However, optimizing the wick structures to increase the dry-out heat flux is challenging due to the complexities in modeling the liquid-vapor interface and the flow through the wick structures. In this work, we developed a model for thin-film evaporation from micropillar array wick structures and validated the model with experiments. The model numerically simulates liquid velocity, pressure, and meniscus curvature along the wicking direction by conservation of mass, momentum, and energy based on a finite volume approach. Specifically, the three-dimensional meniscus shape, which varies along the wicking direction with the local liquid pressure, is accurately captured by a force balance using the Young-Laplace equation. The dry-out condition is determined when the minimum contact angle on the pillar surface reaches the receding contact angle as the applied heat flux increases. With this model, we predict the dry-out heat flux on various micropillar structure geometries (diameter, pitch, and height) in the length scale range of 1-100 MUm and discuss the optimal geometries to maximize the dry-out heat flux. We also performed detailed experiments to validate the model predictions, which show good agreement. This work provides insights into the role of surface structures in thin-film evaporation and offers important design guidelines for enhanced thermal management of high-performance electronic devices. PMID- 26808964 TI - Breeding under unpredictable conditions: Annual variation in gonadal maturation, energetic reserves and plasma levels of androgens and corticosterone in anurans from the Brazilian semi-arid. AB - Anurans living in arid and semi-arid habitats are subjected to unpredictable rain patterns. Consequently, they should be prepared to reproduce at the onset of rain events. We investigated the covariation between calling behavior, testicular maturation, abdominal fat body index (FBI), plasma levels of androgens (T-DHT) and corticosterone (CORT) of males from three species of anurans in the Brazilian semi-arid during the reproductive period and drought. One of these species aestivates during the drought, while the other two species remain foraging. Although the three species display different behavioral strategies during the dry period, they present the same general reproductive patterns. T-DHT levels on the plasma and germinative cyst diameters were higher during the reproductive and breeding period compared to the drought. Additionally, the germinative cysts had all cell stages including sperm bundles during the dry season, however, it was only during the breeding event that free spermatozoa were found in the cyst lumen. These results suggest that these species present the reproductive pattern typical of desert anurans, consisting of opportunistic breeders that reproduce when triggered by a rain stimulus. Rhinella jimi and Pleurodema diplolister had higher CORT when males were calling. Moreover, Rhinella granulosa and P. diplolister showed lower FBI during breeding event, when males were calling. The high levels of CORT and lower FBI during reproductive period are associated, indicating that CORT modulates the recruitment of energy stores to prepare and maintain reproduction, particularly the expensive calling effort. PMID- 26808965 TI - Testosterone secretion in a socially monogamous but sexually promiscuous migratory passerine. AB - The steroid hormone testosterone (T) influences a multitude of traits critical to reproduction in vertebrates. In birds, high male T supports territory establishment and mate attraction, but is thought to interfere with parental care. Interspecific comparisons indicate that migratory species with short, synchronous breeding seasons have the highest peak T, and that the seasonal profile of T exhibits a rapid decline with the onset of incubation by females. We describe the T profile of the migratory, socially monogamous, and biparental Eastern Kingbird (Tyrannus tyrannus) from the high desert of eastern Oregon, USA, where breeding occurs within a short 2-3 month period. Eastern Kingbirds are socially monogamous but exhibit high rates of extra-pair paternity as ~60% of broods contain extra-pair young. We therefore evaluate whether Eastern Kingbirds exhibit the "typical" T profile expected for a synchronously breeding migratory species, or whether T is maintained at a more constant level as would be predicted for a species with opportunities for mating that extend over a majority of the breeding season. Our samples were divided into six periods of the reproductive cycle from territory establishment to the feeding of fledglings. T did not change across stages of the nest cycle. Instead, T declined with sampling date and nest density, and increased with the number of fertile females in the population. Male kingbirds advertise their presence through song for most of the breeding season, and we suggest that T is maintained throughout most of the breeding season because male fitness is equally dependent on within- and extra pair reproductive success. PMID- 26808966 TI - Posttraumatic Stress and Depression in the Nonoffending Caregivers of Sexually Abused Children: Associations With Parenting Practices. AB - Caregiver mental health is a known correlate of parenting practices, and recent research indicated that parental depression following childhood sexual abuse disclosure is associated with concurrent parenting difficulties. The present study extended this line of research by investigating posttraumatic stress symptoms and depression in a sample of caregivers (N = 96) of children who experienced sexual abuse recruited from a child advocacy center as well as parenting practices reported by both caregivers and their children (mean age = 10.79 years, SD = 3.29; 79% female). Twenty-four percent of caregivers met criteria for presumptive clinical depression, clinically significant posttraumatic stress, or both. Results indicated elevated caregiver-reported inconsistent parenting in the context of clinically significant distress across symptom groups; children reported particularly elevated inconsistent parenting for caregivers with posttraumatic stress only. Caregiver depression was associated with low self-reported positive parenting and caregiver involvement in addition to self-reported inconsistencies. Directions for future research are offered to further elucidate the relationships between caregiver mental health and parenting practices following childhood sexual abuse. PMID- 26808967 TI - Prevalence and Associated Factors of Diabetes Mellitus among Tuberculosis Patients in South-Eastern Amhara Region, Ethiopia: A Cross Sectional Study. AB - BACKGROUND: The association between diabetes mellitus (DM) and tuberculosis (TB) is re-emerging worldwide. Recently, the prevalence of DM is increasing in resource poor countries where TB is of high burden. The objective of the current study was to determine the prevalence and analyze associated factors of TB and DM comorbidity in South-Eastern Amhara Region, Ethiopia. METHODS: This was a facility based cross-sectional study. All newly diagnosed TB patients attending selected health facilities in the study area were consecutively screened for DM. DM was diagnosed based on the World Health Organization diagnostic criteria. A pre-tested semi-structured questionnaire was used to collect socio-demographic, lifestyles and clinical data. Logistic regression analysis was performed to identify factors associated with TB and DM comorbidity. RESULT: Among a total of 1314 patients who participated in the study, the prevalence of DM was estimated at 109 (8.3%). Being female [odds ratio (OR) 1.70; 95% confidence interval (CI) (1.10-2.62)], patients age [41-64 years (OR 3.35; 95% CI (2.01-5.57), 65-89 years (OR 3.18; 95% CI (1.52-6.64)], being a pulmonary TB case [(OR 1.69; 95% CI 1.09 2.63)] and having a family history of DM [(OR 4.54; 95% CI (2.36-8.73)] were associated factors identified with TB and DM comorbidity. CONCLUSION: The prevalence of DM among TB patients in South-Eastern Amahra Region is high. Routine screening of TB patients for DM is recommended in the study area. PMID- 26808968 TI - Utility of an Internal Retractor (EndoGrab) for the Management of the Vesicouterine Ligament during Laparoscopic Radical Hysterectomy. AB - BACKGROUND/AIMS: The study aims to prevent serious urologic injury during a radical hysterectomy; we propose that one of the most important procedural steps is the careful management of the vesicouterine ligament (VUL). PATIENTS AND METHODS: Between January 2013 and October 2014, we used a novel internal retractor in 17 patients undergoing a laparoscopic radical hysterectomy (LRH) for early-stage cervical cancer to obtain and secure a better surgical view. For management of the VUL during the laparoscopic procedure, we routinely used an internal retractor (EndoGrab; Virtual Ports, Misgav, Israel) and vessel tape to reposition the ureter in a safe lateral-caudal direction. RESULTS: Using an EndoGrab, we were easily able to reproduce a suitable surgical view that simulated the one obtained by an abdominal route for radical hysterectomy. Using this improved laparoscopic procedure, we completed radical hysterectomies in all 17 cases without a ureteral injury complication. CONCLUSION: Our modified method using an EndoGrab is effective for the prevention of ureteral injury during a LRH, and its ease of use makes it suitable even for those surgeons early in their laparoscopic learning curve. PMID- 26808969 TI - Location, location, location: PDE4D5 function is directed by its unique N terminal region. PMID- 26808970 TI - Effect of Copper and Zinc on the Single Molecule Self-Affinity of Alzheimer's Amyloid-beta Peptides. AB - The presence of trace concentrations of metallic ions, such as copper and zinc, has previously been shown to drastically increase the aggregation rate and neurotoxicity of amyloid-beta (Abeta), the peptide implicated in Alzheimer's disease (AD). The mechanism of why copper and zinc accelerate Abeta aggregation is poorly understood. In this work, we use single molecule force spectroscopy (SMFS) to probe the kinetic and thermodynamic parameters (dissociation constant, Kd, kinetic dissociation rate, koff, and free energy, DeltaG) of the dissociation of an Abeta dimer, the amyloid species which initiates the amyloid cascade. Our results show that nanomolar concentrations of copper do not change the single molecule affinity of Abeta to another Abeta peptide in a statistically significant way, while nanomolar concentrations of zinc decrease the affinity of Abeta-Abeta by an order of magnitude. This suggests that the binding of zinc ion to Abeta may interfere with the binding of Abeta-Abeta, leading to a lower self affinity. PMID- 26808971 TI - Measurement of Heart Rate Variability to Assess Pain in Sedated Critically Ill Patients: A Prospective Observational Study. AB - INTRODUCTION: The analgesia nociception index (ANI) assesses the relative parasympathetic tone as a surrogate for antinociception/nociception balance in sedated patients. The aim of this study is to determine the effectiveness of ANI in detecting pain in deeply sedated critically ill patients. METHODS: This prospective observational study was performed in two medical ICUs. All patients receiving invasive mechanical ventilation and deep sedation were eligible. In all patients, heart rate and ANI were continuously recorded using the Physiodoloris(r) device during 5 minutes at rest (T1), during a painful stimulus (T2), and during 5 minutes after the end of the painful stimulus (T3). The chosen painful stimulus was patient turning for washstand. Pain was evaluated at T2, using the behavioral pain scale (BPS). The primary objective was to determine the effectiveness of ANI in detecting pain. Secondary objectives included the impact of norepinephrine on the effectiveness of ANI in detecting pain, and the correlation between ANI and BPS. RESULTS: Forty-one patients were included. ANI was significantly lower at T2 (Med (IQR) 69(55-78)) compared with T1 (85(67-96), p<0.0001), or T3 (81(63-89), p<0.0001). Similar results were found in the subgroups of patients with (n = 21) or without (n = 20) norepinephrine. ANI values were significantly higher in patients with norepinephrine compared with those without norepinephrine at T1, and T2. No significant correlation was found between ANI and BPS at T2. CONCLUSIONS: ANI is effective in detecting pain in deeply sedated critically ill patients, including those patients treated with norepinephrine. No significant correlation was found between ANI and BPS. PMID- 26808972 TI - Bohr effect and temperature sensitivity of hemoglobins from highland and lowland deer mice. AB - An important means of physiological adaptation to environmental hypoxia is an increased oxygen (O2) affinity of the hemoglobin (Hb) that can help secure high O2 saturation of arterial blood. However, the trade-off associated with a high Hb O2 affinity is that it can compromise O2 unloading in the systemic capillaries. High-altitude deer mice (Peromyscus maniculatus) have evolved an increased Hb-O2 affinity relative to lowland conspecifics, but it is not known whether they have also evolved compensatory mechanisms to facilitate O2 unloading to respiring tissues. Here we investigate the effects of pH (Bohr effect) and temperature on the O2-affinity of high- and low-altitude deer mouse Hb variants, as these properties can potentially facilitate O2 unloading to metabolizing tissues. Our experiments revealed that Bohr factors for the high- and low-altitude Hb variants are very similar in spite of the differences in O2-affinity. The Bohr factors of deer mouse Hbs are also comparable to those of other mammalian Hbs. In contrast, the high- and low-altitude variants of deer mouse Hb exhibited similarly low temperature sensitivities that were independent of red blood cell anionic cofactors, suggesting an appreciable endothermic allosteric transition upon oxygenation. In conclusion, high-altitude deer mice have evolved an adaptive increase in Hb-O2 affinity, but this is not associated with compensatory changes in sensitivity to changes in pH or temperature. Instead, it appears that the elevated Hb-O2 affinity in high-altitude deer mice is compensated by an associated increase in the tissue diffusion capacity of O2 (via increased muscle capillarization), which promotes O2 unloading. PMID- 26808973 TI - A Randomized Controlled Trial of Mindfulness-Based Cognitive Therapy for Treatment-Resistant Depression. AB - BACKGROUND: Due to the clinical challenges of treatment-resistant depression (TRD), we evaluated the efficacy of mindfulness-based cognitive therapy (MBCT) relative to a structurally equivalent active comparison condition as adjuncts to treatment-as-usual (TAU) pharmacotherapy in TRD. METHODS: This single-site, randomized controlled trial compared 8-week courses of MBCT and the Health Enhancement Program (HEP), comprising physical fitness, music therapy and nutritional education, as adjuncts to TAU pharmacotherapy for outpatient adults with TRD. The primary outcome was change in depression severity, measured by percent reduction in the total score on the 17-item Hamilton Depression Rating Scale (HAM-D17), with secondary depression indicators of treatment response and remission. RESULTS: We enrolled 173 adults; mean length of a current depressive episode was 6.8 years (SD = 8.9). At the end of 8 weeks of treatment, a multivariate analysis showed that relative to the HEP condition, the MBCT condition was associated with a significantly greater mean percent reduction in the HAM-D17 (36.6 vs. 25.3%; p = 0.01) and a significantly higher rate of treatment responders (30.3 vs. 15.3%; p = 0.03). Although numerically superior for MBCT than for HEP, the rates of remission did not significantly differ between treatments (22.4 vs. 13.9%; p = 0.15). In these models, state anxiety, perceived stress and the presence of personality disorder had adverse effects on outcomes. CONCLUSIONS: MBCT significantly decreased depression severity and improved treatment response rates at 8 weeks but not remission rates. MBCT appears to be a viable adjunct in the management of TRD. PMID- 26808975 TI - Aquaporin 3 is regulated by estrogen in the chicken oviduct and is involved in progression of epithelial cell-derived ovarian carcinomas. AB - Aquaporins (AQPs) are membrane proteins that passively deliver water across the plasma membrane to play an important role in maintaining cell shape. Members of the AQP family are distributed in most of the tissues in the human body and perform a variety of functions based on the water homeostasis suitable for each organ. However, there is little known about the expression and regulation of AQP family members in chickens. Therefore, we determined the expression of AQPs in various tissues of chickens. Among 13 isotypes, AQP3 was highly expressed in the chicken oviduct. Expression of AQP3 messenger RNA (mRNA) increased in the magnum (P < 0.001) and isthmus (P < 0.001) of chick oviducts treated with diethylstilbestrol. Consistent with these results, the localization of AQP3 was detected in the glandular and luminal epithelia of the magnum and isthmus of oviducts of diethylstilbestrol-treated chicks. In addition, the pattern of expression of AQP3 changed in an estrogen-dependent manner during the molting period. During the regenerative period of the oviduct after molting, expression of AQP3 mRNA increased coordinately with increasing concentrations of estradiol (P < 0.001), whereas expression of AQP3 mRNA decreased as concentrations of estradiol in plasma decreased in response to induced molting (P < 0.001). Also, expression of the AQP3 increased (P < 0.001) in cancerous ovaries of laying hens. In conclusion, AQP3 does not simply function to transport water into and out of cells but also appears to be closely involved in development of the chicken oviduct, which is regulated by estrogens. Furthermore, our results suggest AQP3 as a new diagnostic for early detection and treatment of epithelial cell-derived ovarian carcinomas. PMID- 26808974 TI - Alterations in Lipid and Inositol Metabolisms in Two Dopaminergic Disorders. AB - BACKGROUND: Serum metabolite profiling can be used to identify pathways involved in the pathogenesis of and potential biomarkers for a given disease. Both restless legs syndrome (RLS) and Parkinson's disease (PD) represent movement disorders for which currently no blood-based biomarkers are available and whose pathogenesis has not been uncovered conclusively. We performed unbiased serum metabolite profiling in search of signature metabolic changes for both diseases. METHODS: 456 metabolites were quantified in serum samples of 1272 general population controls belonging to the KORA cohort, 82 PD cases and 95 RLS cases by liquid-phase chromatography and gas chromatography separation coupled with tandem mass spectrometry. Genetically determined metabotypes were calculated using genome-wide genotyping data for the 1272 general population controls. RESULTS: After stringent quality control, we identified decreased levels of long-chain (polyunsaturated) fatty acids of individuals with PD compared to both RLS (PD vs. RLS: p = 0.0001 to 5.80x10-9) and general population controls (PD vs. KORA: p = 6.09x10-5 to 3.45x10-32). In RLS, inositol metabolites were increased specifically (RLS vs. KORA: p = 1.35x10-6 to 3.96x10-7). The impact of dopaminergic drugs was reflected in changes in the phenylalanine/tyrosine/dopamine metabolism observed in both individuals with RLS and PD. CONCLUSIONS: A first discovery approach using serum metabolite profiling in two dopamine-related movement disorders compared to a large general population sample identified significant alterations in the polyunsaturated fatty acid metabolism in PD and implicated the inositol metabolism in RLS. These results provide a starting point for further studies investigating new perspectives on factors involved in the pathogenesis of the two diseases as well as possible points of therapeutic intervention. PMID- 26808976 TI - Concentrations of progesterone, a metabolite of PGF2alpha, prolactin, and luteinizing hormone during development of idiopathic persistent corpus luteum in mares. AB - In experiment 1, daily blood samples were available from Days 0 to 20 (Day 0 = ovulation) in mares with an interovulatory interval (IOI, n = 5) and in mares that developed idiopathic persistent corpus luteum (PCL, n = 5). The PCL was confirmed by maintenance of progesterone (P4) concentration until end of the experiment (Day 20). Significant interactions of group and day revealed the novel findings that luteinizing hormone (LH) was lower (P < 0.05) in the PCL group than that in the IOI group on Days 0 to 4, and prolactin was lower (P < 0.05) on Days 1, 4, 6, and 7. In experiment 2, treatment with a gonadotropin-releasing hormone antagonist (n = 6) significantly reduced LH on Days 1 to 6 compared with the controls (n = 6) but did not support the hypothesis that low LH during the postovulatory period increases the frequency of PCL. In experiment 3, P4, PGFM (a PGF2alpha metabolite), and prolactin concentrations on Days 12 to 20 from 2 reported experiments were combined to increase the number of mares with an IOI (n = 11) or a PCL (n = 11). An abrupt and complete decrease in P4 (luteolysis) began on Day 13 in the IOI group compared with a gradual and partial P4 decline after Day 12 in the PCL group. Concentrations of PGFM and prolactin were lower (P < 0.05) in the PCL group than those in the IOI group on the day at the end of the most pronounced decrease in P4. The PCL mares were subgrouped into those with an abrupt but incomplete P4 decrease (partial luteolysis; n = 5) at the expected time and those without partial luteolysis (n = 6). There were no significant differences between the 2 subgroups in concentrations of PGFM and prolactin, but on a tentative basis (P < 0.10), the concentration of PGFM seemed more focused on the day of the most pronounced decrease in P4 in the subgroup with partial luteolysis. Results for PCL compared with IOI indicated (1) postovulatory LH and prolactin were lower, (2) treatment to reduce postovulatory LH did not increase the incidence, and (3) both PGFM and prolactin were lower on the day of the most pronounced decrease in P4. PMID- 26808977 TI - Plasma concentrations of acyl-ghrelin are associated with average daily gain and feeding behavior in grow-finish pigs. AB - The objectives of this study were to determine the effect of sex, sire line, and litter size on concentrations of acyl-ghrelin and total ghrelin in plasma of grow finish pigs and to understand the relationship of plasma concentrations of ghrelin with feeding behavior, average daily gain (ADG), and back fat in grow finish swine. Yorkshire-Landrace crossbred dams were inseminated with semen from Yorkshire, Landrace, or Duroc sires. Within 24 h of birth, pigs were cross fostered into litter sizes of normal (N; >12 pigs/litter) or small (S; <= 9 pigs/litter). At 8 wk of age, pigs (n = 240) were blocked by sire breed, sex, and litter size and assigned to pens (n = 6) containing commercial feeders modified with a system to monitor feeding behavior. Total time eating, number of daily meals, and duration of meals were recorded for each individual pig. Body weight was recorded every 4 wk. Back fat and loin eye area were recorded at the conclusion of the 12-wk feeding study. A blood sample was collected at week 7 of the study to quantify concentrations of acyl- and total ghrelin in plasma. Pigs from small litters weighed more (P < 0.05) and tended (P = 0.07) to be fatter than pigs from normal litters. Postnatal litter size did not affect ADG, feeding behavior, or concentrations of ghrelin in plasma during the grow-finish phase. Barrows spent more time eating (P < 0.001) than gilts, but the number of meals and concentrations of ghrelin did not differ with sex of the pig. Pigs from Duroc and Yorkshire sires had lesser (P < 0.0001) concentrations of acyl-ghrelin than pigs from Landrace sires, but plasma concentrations of total ghrelin were not affected by sire breed. Concentrations of acyl-ghrelin were positively correlated with the number of meals and negatively correlated with meal length and ADG (P < 0.05). A larger number of short-duration meals may indicate that pigs with greater concentrations of acyl-ghrelin consumed less total feed, which likely explains why they were leaner and grew more slowly. Acyl-ghrelin is involved in regulating feeding behavior in pigs, and measuring acyl-ghrelin is important when trying to understand the role of this hormone in swine physiology. PMID- 26808978 TI - A Sero-epidemiological Approach to Explore Transmission of Mycobacterium ulcerans. AB - The debilitating skin disease Buruli ulcer (BU) is caused by infection with Mycobacterium ulcerans. While various hypotheses on potential reservoirs and vectors of M. ulcerans exist, the mode of transmission has remained unclear. Epidemiological studies have indicated that children below the age of four are less exposed to the pathogen and at lower risk of developing BU than older children. In the present study we compared the age at which children begin to develop antibody responses against M. ulcerans with the age pattern of responses to other pathogens transmitted by various mechanisms. A total of 1,352 sera from individuals living in the BU endemic Offin river valley of Ghana were included in the study. While first serological responses to the mosquito transmitted malaria parasite Plasmodium falciparum and to soil transmitted Strongyloides helminths emerged around the age of one and two years, sero-conversion for M. ulcerans and for the water transmitted trematode Schistosoma mansoni occurred at around four and five years, respectively. Our data suggest that exposure to M. ulcerans intensifies strongly at the age when children start to have more intense contact with the environment, outside the small movement range of young children. Further results from our serological investigations in the Offin river valley also indicate ongoing transmission of Treponema pallidum, the causative agent of yaws. PMID- 26808979 TI - Visual Impairment, Hearing Loss and Cognitive Function in an Older Population: Longitudinal Findings from the Blue Mountains Eye Study. AB - The presence of visual impairment (VI) and hearing loss (HL) with may be a marker for subsequent cognitive decline over time in older people. A prospective, longitudinal population-based study of the 3654 participants of the Blue Mountains Eye Study were assessed for the associations between VI and HL and a decline in mini-mental state examination (MMSE) scores over a duration of 10 years from the 5-year (baseline of this report) to the 15-year follow-up visits. MMSE was assessed at the 5-, 10- and 15-year follow-up visits. A decline >=3 scores from 5-year to 10- or 15-year visits indicated possible cognitive decline. VI was defined as best-corrected visual acuity <6/12 in the worse-eye, HL was defined as pure-tone average >40 decibels in the worse-ear and dual sensory impairment (DSI) was defined by the co-presence of VI and HL, detected at 5-year follow-up (baseline of this report). Participants with no VI and HL over the same 5- or 10-year corresponding period were controls. Associations of VI, HL and DSI with possible cognitive decline were assessed using logistic regression models adjusting for age and sex after excluding subjects with a stroke history. The presence of VI, HL or DSI was not associated with possible cognitive decline over 5 years (odds ratio (OR) 0.84, 95% confidence-intervals (CI) 0.40-1.79, OR 1.02, 95% CI 0.61-1.70 and 1.41, 95% CI 0.54-3.72, respectively) or 10 years (OR 1.09, 95% CI 0.52-2.30, OR 1.09, 95% CI 0.65-1.82 and 1.15, 95% CI 0.28-4.73, respectively). There were no changes to these findings after adjustment for other potential confounders. Age was significantly associated with possible cognitive decline (OR 1.07, 95% CI 1.04-1.10 for both periods). Neither visual impairment, hearing loss nor dual sensory impairment was independently associated with subsequent decline in cognition. PMID- 26808980 TI - Role of Muscarinic Acetylcholine Receptors in Serial Feature-Positive Discrimination Task during Eyeblink Conditioning in Mice. AB - We investigated the role of muscarinic acetylcholine receptors (mAChRs) in eyeblink serial feature-positive discrimination learning in mice using the mAChR antagonist. A 2-s light cue was delivered 5 or 6 s before the presentation of a 350-ms tone paired with a 100-ms periorbital electrical shock (cued trial) but not before the tone-alone presentation (non-cued trial). Mice received 30 cued and 30 non-cued trials each day in a random order. We found that saline-injected control mice were successfully discriminating between cued and non-cued trials within a few days of conditioning. The mice responded more frequently to the tone in cued trials than in non-cued trials. Analysis of conditioned response (CR) dynamics revealed that the CR onset latency was shorter in cued trials than in non-cued trials, despite the CR peak amplitude not differing significantly between the two conditions. In contrast, scopolamine-injected mice developed an equal number of CRs with similar temporal patterns irrespective of the presence of the cue during the 7 days of conditioning, indicating in a failure to acquire conditional discrimination. In addition, the scopolamine administration to the control mice after they had successfully acquired discrimination did not impair the conditional discrimination and expression of pre-acquired CR. These results suggest that mAChRs may play a pivotal role in memory formation in the conditional brain state associated with the feature cue; however they are unlikely to be involved in the development of discrimination after conditional memory had formed in the serial feature-positive discrimination task during eyeblink conditioning. PMID- 26808981 TI - Efficacy and long-term outcomes of palivizumab prophylaxis to prevent respiratory syncytial virus infection in infants with cystic fibrosis in Northern Ireland. AB - BACKGROUND: RSV causes considerable morbidity and mortality in children. In cystic fibrosis (CF) viral infections are associated with worsening respiratory symptoms and bacterial colonization. Palivizumab is effective in reducing RSV hospitalization in high risk patient groups. Evidence regarding its effectiveness and safety in CF is inconclusive. CF screening in N. Ireland enabled timely palivizumab prophylaxis, becoming routine in 2002. OBJECTIVES: To determine the effect of palivizumab on RSV-related hospitalization and compare lung function and bacterial colonization at age 6 years for those born pre- and post introduction of palivizumab prophylaxis. METHODS: A retrospective audit was conducted for all patients diagnosed with CF during the period from 1997 to 2007 inclusive. RSV-related hospitalization, time to Pseudomonas aeruginosa (PA) 1st isolate, lung function and growth parameters were recorded. Comparisons were made for outcomes pre- and post-introduction of routine palivizumab administration in 2002. A cost evaluation was also performed. RESULTS: Ninety-two children were included; 47 pre- and 45 post-palivizumab introduction. The overall RSV-positive hospitalization rate was 13%. The relative risk of RSV infection in palivizumab non-recipients versus recipients was 4.78 (95%CI: 1.1-20.7), P = 0.027. Notably, PA 1st isolate was significantly earlier in the palivizumab recipient cohort versus non-recipient cohort (median 57 vs. 96 months, P < 0.025) with a relative risk of 2.5. Chronic PA infection at 6 years remained low in both groups, with similar lung function and growth parameters. Total costs were calculated at L96,127 ($151,880) for the non-recipient cohort versus L137,954 ($217,967) for the recipient cohort. CONCLUSION: Palivizumab was effective in reducing RSV related hospitalization infection in CF patients. Surprisingly, we found a significantly earlier time to 1st isolate of PA in palivizumab recipients which we could not explain by altered or improved diagnostic tests. PMID- 26808982 TI - Application of Diffusion Tensor Imaging Parameters to Detect Change in Longitudinal Studies in Cerebral Small Vessel Disease. AB - Cerebral small vessel disease (SVD) is the major cause of vascular cognitive impairment, resulting in significant disability and reduced quality of life. Cognitive tests have been shown to be insensitive to change in longitudinal studies and, therefore, sensitive surrogate markers are needed to monitor disease progression and assess treatment effects in clinical trials. Diffusion tensor imaging (DTI) is thought to offer great potential in this regard. Sensitivity of the various parameters that can be derived from DTI is however unknown. We aimed to evaluate the differential sensitivity of DTI markers to detect SVD progression, and to estimate sample sizes required to assess therapeutic interventions aimed at halting decline based on DTI data. We investigated 99 patients with symptomatic SVD, defined as clinical lacunar syndrome with MRI confirmation of a corresponding infarct as well as confluent white matter hyperintensities over a 3 year follow-up period. We evaluated change in DTI histogram parameters using linear mixed effect models and calculated sample size estimates. Over a three-year follow-up period we observed a decline in fractional anisotropy and increase in diffusivity in white matter tissue and most parameters changed significantly. Mean diffusivity peak height was the most sensitive marker for SVD progression as it had the smallest sample size estimate. This suggests disease progression can be monitored sensitively using DTI histogram analysis and confirms DTI's potential as surrogate marker for SVD. PMID- 26808984 TI - Correction: The Values of Combined and Sub-Stratified Imaging Scores with Ultrasonography and Mammography in Breast Cancer Subtypes. PMID- 26808983 TI - Photo-switchable tweezers illuminate pore-opening motions of an ATP-gated P2X ion channel. AB - P2X receptors function by opening a transmembrane pore in response to extracellular ATP. Recent crystal structures solved in apo and ATP-bound states revealed molecular motions of the extracellular domain following agonist binding. However, the mechanism of pore opening still remains controversial. Here we use photo-switchable cross-linkers as 'molecular tweezers' to monitor a series of inter-residue distances in the transmembrane domain of the P2X2 receptor during activation. These experimentally based structural constraints combined with computational studies provide high-resolution models of the channel in the open and closed states. We show that the extent of the outer pore expansion is significantly reduced compared to the ATP-bound structure. Our data further reveal that the inner and outer ends of adjacent pore-lining helices come closer during opening, likely through a hinge-bending motion. These results provide new insight into the gating mechanism of P2X receptors and establish a versatile strategy applicable to other membrane proteins. PMID- 26808985 TI - Characterization of the observe zone of the ESC 2015 high-sensitivity cardiac troponin 0h/1h-algorithm for the early diagnosis of acute myocardial infarction. AB - OBJECTIVE: The novel high-sensitivity cardiac troponin (hs-cTn) 0h/1h-algorithm substantially improves the early triage of patient's assigned "rule-out" or "rule in" of acute myocardial infarction (AMI), while diagnostic uncertainty remains in that 25-30% of patients assigned to "observe". We aimed to better characterize these patients. METHODS: In a prospective multicenter diagnostic study, we applied the hs-cTnT 0h/1h-algorithm in 2213 unselected patients presenting with symptoms suggestive of AMI to the emergency department. The final diagnosis was adjudicated by two independent cardiologists using all available information. Survival at 720-days was the prognostic endpoint. Findings were validated using a hs-cTnI 0h/1h-algorithm. RESULTS: Twenty-four percent (n=523) of patients were assigned to "observe" by the hs-cTnT 0h/1h-algorithm. These patients differed significantly in multiple characteristics from "rule-out" and "rule-in" patients: they were older, in 75% male, and very often (57%) had pre-existing coronary artery disease (CAD). Diagnostic uncertainty for the presence of an AMI/UA was high. Only 39% of patients were suitable for coronary computed tomography angiography (CCTA). The most common final adjudicated diagnoses were non-cardiac disease (38%), non-coronary cardiac disease (24%), unstable angina (UA, 21%), and AMI (15%). Absolute hs-cTnT-changes within 3h had the highest diagnostic accuracy for AMI (AUC 0.86). Cumulative 720-day survival rate was 86%, which was significantly lower as compared to "rule-out" (p<0.001) and comparable to "rule in" (p=ns). Findings were similar for the hs-cTnI "observe" zone. CONCLUSION: "Observe" patients are typically elderly men with pre-existing CAD and high long term mortality. Absolute hs-cTn-changes within 3h, functional stress imaging and coronary angiography are the key diagnostic modalities. PMID- 26808986 TI - Self-reported sleep duration and coronary heart disease mortality: A large cohort study of 400,000 Taiwanese adults. AB - BACKGROUND: Most previous studies on sleep duration and coronary heart disease (CHD) have been small and have inadequately controlled for cardiovascular risk factors and chronic diseases. Therefore, our aim was to prospectively examine the associations of sleep duration with CHD while accounting for these factors. METHODS: Prospective cohort study of 392 164 adults at age 20years or older who attended a health check-up program from 1994 to 2011 in Taiwan and who have information on sleep duration, sleep medications and potential confounders. Participants answered the question: "How long do you sleep for?"-there were four response categories: (a) 0-4h; (b) 4-6h; (c) 6-8h and (d) >8h. The participants were then followed for CHD mortality from the Taiwanese cause-of-death register. RESULTS: When compared to those who slept 6-8h per night, the risk of dying from CHD was increased by 34% (HR 1.34, 95% Confidence Interval [CI] 0.87-2.07) and 35% (HR 1.35, 95% CI 1.11-1.65) in those who slept less than 4h per night and more than 8h per night, respectively. When stratifying by sex and age, we found some evidence for a stronger U-shaped association in females than in males and in older adults than in younger adults (p for interaction=0.01 and 0.13, respectively). CONCLUSIONS: Adequate sleep duration should be considered an important component of a healthy lifestyle. Further studies are needed to better elucidate the underlying mechanisms. PMID- 26808987 TI - Incidence and risk factors for severe renal impairment after first diagnosis of heart failure: A cohort and nested case-control study in UK general practice. AB - OBJECTIVE: We aimed to evaluate the incidence, time-course and risk factors for severe renal impairment (SRI) among incident heart failure (HF) patients. METHODS AND RESULTS: Patients aged 1-89years from 2000 to 2005 with incident HF and without SRI or cancer (N=18,049) were identified from The Health Improvement Network (a primary care database representative of the UK population). Patients with a first ever record of SRI during follow-up were identified and eligible non cases used as controls (N=5377; mean age 74years). Cohort and nested case-control analyses were conducted to identify risk factors for SRI. 2818 patients (15.6%, mean age 75years) in the HF cohort developed SRI over a mean of 2.84years with incidence highest in the first year following HF diagnosis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were as follows: diabetes (1.96, 1.80-2.14), hypertension (1.23, 1.14-1.33), peripheral artery disease (1.29, 1.15-1.45), ischemic cerebrovascular disease (1.14, 1.03-1.26), and anemia (1.19, 1.06-1.34). Several cardiovascular medications were associated with SRI in the case-control analysis, odds ratios (95% CIs): 5.07 (3.87-6.64) for all diuretics, 3.22 (2.83 3.66) for potassium-sparing diuretics, 2.40 (1.96-2.93) for thiazide and related diuretics and 3.27 (2.67-4.01) for loop-diuretics. CONCLUSION: SRI is a frequent complication in patients with newly diagnosed HF. Comorbidities may contribute to its development and should be adequately treated. Robust clinical trial data on beneficial or possibly deleterious effects of diuretics, especially loop diuretics and potassium-sparing diuretics, on SRI development in HF patients are warranted. PMID- 26808988 TI - Relation of female sex to left atrial diameter and cardiovascular death in atrial fibrillation: The AFFIRM Trial. AB - BACKGROUND: Female sex is associated with thromboembolism related to atrial fibrillation (AF). Left atrial (LA) diameter independently predicted incident cardiovascular (CV) major events in the general population. In AF patients, LA enlargement is associated to AF occurrence and recurrence. No data have previously been reported on the relationship between LA enlargement, sex and CV death in AF patients. METHODS AND RESULTS: All patients enrolled in the AFFIRM Trial with available data about LA dimension were included in this post-hoc analysis. Of the 2615 eligible for the present analysis, LA enlargement was recorded in 67.0%, more commonly in women than in men (p=0.032). Patients with LA enlargement had higher body mass index (BMI), and were more frequently hypertensive, diabetic, and diagnosed with a structural heart disease, prior coronary artery disease (CAD) and heart failure (HF). BMI, left ventricular mass, female sex and mitral valve insufficiency (p<0.001) were associated with LA enlargement. AF female patients with LA enlargement had a higher risk for CV death (p=0.011). LA diameter showed a significant association with CV death (p<0.001). Cox regression analysis demonstrated that LA diameter was an independent predictor of CV death in female AF patients (p=0.003). CONCLUSIONS: LA diameter enlargement is associated with female sex, and carries a higher risk for CV death, particularly in females. LA diameter was an independent predictor of CV death in female AF patients. PMID- 26808989 TI - Is non-sustained ventricular tachycardia a predictor of sudden death in adults with congenital heart disease? PMID- 26808990 TI - Vegetation in the coronary sinus that concealed the presence of a coronary arteriovenous fistula in a patient with infectious endocarditis. PMID- 26808991 TI - Impact of gender on infarct size, ST-segment resolution, myocardial blush and clinical outcomes after primary stenting for acute myocardial infarction: Substudy from the EMERALD trial. AB - BACKGROUND: Women with AMI may have worse outcomes than men. However, it is unclear if this is related to differences in treatment, treatment effect or gender specific factors. We sought to determine whether primary percutaneous intervention (PCI) has a differential impact on infarct size, myocardial perfusion and ST segment resolution in men and women with acute myocardial infarction (AMI). METHODS: A total of 501 AMI patients were prospectively enrolled in the EMERALD study and underwent PCI with or without distal protection. Post hoc gender subset analysis was performed. RESULTS: 501 patients (108 women, 393 men) with ST-segment elevation AMI presenting within 6h underwent primary (or rescue) PCI with stenting and a distal protection device. Women were older, had more hypertension, less prior AMI, smaller BSA, and smaller vessel size, but had similar rates of diabetes (30% versus 20.2%, p=0.87), LAD infarct, and time-to-reperfusion compared to men. Women more frequently had complete ST resolution (>70%) at 30days (72.8% versus 59.8%, p=0.02), and smaller infarct size compared to males (12.2+/-19.6% versus 18.4+/-18.5%, p=0.006). At 6months, TLR (6.9% versus 5.2%) and MACE (11.4% versus 10.3%) were similar for women and men. CONCLUSIONS: Despite worse comorbidities, women with AMI treated with primary PCI with stenting showed similar early and midterm outcomes compared to men. PMID- 26808992 TI - Reply to the letter "thioredoxin-1 (Trx1) engineered mesenchymal stem cell therapy is a promising feasible therapeutic approach for myocardial infarction". PMID- 26808993 TI - Serial galectin-3 for the monitoring of optimally treated stable chronic heart failure: A pilot study. PMID- 26808994 TI - Unravelling the Biodiversity and Molecular Phylogeny of Needle Nematodes of the Genus Longidorus (Nematoda: Longidoridae) in Olive and a Description of Six New Species. AB - The genus Longidorus includes a remarkable group of invertebrate animals of the phylum Nematoda comprising polyphagous root-ectoparasites of numerous plants including several agricultural crops and trees. Damage is caused by direct feeding on root cells as well as by transmitting nepoviruses that cause disease on those crops. Thus, correct identification of Longidorus species is essential to establish appropriate control measures. We provide the first detailed information on the diversity and distribution of Longidorus species infesting wild and cultivated olive soils in a wide-region in southern Spain that included 159 locations from which 449 sampling sites were analyzed. The present study doubles the known biodiversity of Longidorus species identified in olives by including six new species (Longidorus indalus sp. nov., Longidorus macrodorus sp. nov., Longidorus onubensis sp. nov., Longidorus silvestris sp. nov., Longidorus vallensis sp. nov., and Longidorus wicuolea sp. nov.), two new records for wild and cultivate olives (L. alvegus and L. vineacola), and two additional new records for wild olive (L. intermedius and L. lusitanicus). We also found evidence of some geographic species associations to western (viz. L. alvegus, L. intermedius, L. lusitanicus, L. onubensis sp. nov., L. vineacola, L. vinearum, L. wicuolea sp. nov.) and eastern distributions (viz. L. indalus sp. nov.), while only L. magnus was detected in both areas. We developed a comparative study by considering morphological and morphometrical features together with molecular data from nuclear ribosomal RNA genes (D2-D3 expansion segments of 28S, ITS1, and partial 18S). Results of molecular and phylogenetic analyses confirmed the morphological hypotheses and allowed the delimitation and discrimination of six new species of the genus described herein and four known species. Phylogenetic analyses of Longidorus spp. based on three molecular markers resulted in a general consensus of these species groups, since lineages were maintained for the majority of species. This study represents the most complete phylogenetic analysis for Longidorus species to date. PMID- 26808995 TI - Comprehensive Immunolocalization Studies of a Putative Serotonin Receptor from the Alimentary Canal of Aedes aegypti Larvae Suggest Its Diverse Roles in Digestion and Homeostasis. AB - Serotonin regulates key processes including digestion and homeostasis in insects. Serotonin effects are mediated by serotonin receptors that transduce information through initiation of second messenger signaling pathways. Lack of information on serotonin receptors associated with the alimentary canal impedes the understanding of the serotonergic role in insect physiology. To address this void, the present study has cloned and identified a putative serotonin receptor (hereafter AaSeR-1) from the alimentary canal of Aedes aegypti (yellow fever mosquito) larvae. In addition to in-silico analyses of AaSeR-1 primary sequence, immunohistochemical investigations were carried out to elucidate receptor expression patterns. Specific AaSeR-1 immunofluorescence was detected in the caeca, the mid- and hindgut, including the Malpighian tubules. These findings point out not only receptor ubiquitous nature but also its involvement in regulation of different stages of nutrient processing and homeostasis. Furthermore, AaSeR-1 may mediate an array of effects through its differential expression at various cell compartments. While AaSeR-1 specific immunofluorescence was depicted in the nucleus and nucleolus of principal cells of the anterior midgut, in the posterior, analyses suggest receptor association with the plasma membrane of both principal and regenerative cells. In addition, AaSeR-1 immunofluorescence was also found in some enteroendocrine cells and in both circular and longitudinal muscles that innervate the alimentary canal. Overall, immunohistochemical analyses of AaSeR-1 expression indicate that this receptor exercises multiple roles in digestion- and homeostasis-related mechanisms. PMID- 26808996 TI - Development of an Extracorporeal Perfusion Device for Small Animal Free Flaps. AB - BACKGROUND: Extracorporeal perfusion (ECP) might prolong the vital storage capabilities of composite free flaps, potentially opening a wide range of clinical applications. Aim of the study was the development a validated low-cost extracorporeal perfusion model for further research in small animal free flaps. METHODS: After establishing optimal perfusion settings, a specially designed extracorporeal perfusion system was evaluated during 8-hour perfusion of rat epigastric flaps followed by microvascular free flap transfer. Controls comprised sham-operation, ischemia and in vivo perfusion. Flaps and perfusate (diluted blood) were closely monitored by blood gas analysis, combined laser Doppler flowmetry and remission spectroscopy and Indocyanine-Green angiography. Evaluations were complemented by assessment of necrotic area and light microscopy at day 7. RESULTS: ECP was established and maintained for 8 hours with constant potassium and pH levels. Subsequent flap transfer was successful. Notably, the rate of necrosis of extracorporeally perfused flaps (27%) was even lower than after in vivo perfusion (49%), although not statistically significant (P = 0,083). After sham-operation, only 6% of the total flap area became necrotic, while 8-hour ischemia led to total flap loss (98%). Angiographic and histological findings confirmed these observations. CONCLUSIONS: Vital storage capabilities of microvascular flaps can be prolonged by temporary ECP. Our study provides important insights on the pathophysiological processes during extracorporeal tissue perfusion and provides a validated small animal perfusion model for further studies. PMID- 26808997 TI - Differential Gene Expression Patterns in Chicken Cardiomyocytes during Hydrogen Peroxide-Induced Apoptosis. AB - Hydrogen peroxide (H2O2) is both an exogenous and endogenous cytotoxic agent that can reliably induce apoptosis in numerous cell types for studies on apoptosis signaling pathways. However, little is known of these apoptotic processes in myocardial cells of chicken, a species prone to progressive heart failure. Sequencing of mRNA transcripts (RNA-Seq) allows for the identification of differentially expressed genes under various physiological and pathological conditions to elucidate the molecular pathways involved, including cellular responses to exogenous and endogenous toxins. We used RNA-seq to examine genes differentially expressed during H2O2-induced apoptosis in primary cultures of embryonic chicken cardiomyocytes. Following control or H2O2 treatment, RNA was extracted and sequencing performed to identify novel transcripts up- or downregulated in the H2O2 treatment group and construct protein-protein interaction networks. Of the 19,268 known and 2,160 novel transcripts identified in both control and H2O2 treatment groups, 4,650 showed significant differential expression. Among them, 55.63% were upregulated and 44.37% downregulated. Initiation of apoptosis by H2O2 was associated with upregulation of caspase-8, caspase-9, and caspase-3, and downregulation of anti-apoptotic genes API5 and TRIA1. Many other differentially expressed genes were associated with metabolic pathways (including 'Fatty acid metabolism', 'Alanine, aspartate, and glutamate metabolism', and 'Biosynthesis of unsaturated fatty acids') and cell signaling pathways (including 'PPAR signaling pathway', 'Adipocytokine signaling pathway', 'TGF-beta signaling pathway', 'MAPK signaling pathway', and 'p53 signaling pathway'). In chicken cardiomyocytes, H2O2 alters the expression of numerous genes linked to cell signaling and metabolism as well as genes directly associated with apoptosis. In particular, H2O2 also affects the biosynthesis and processing of proteins and unsaturated fatty acids. These results highlight the value of RNA-seq for revealing unexpected molecular contributors to oxidative stress responses, thereby identifying novel potential therapeutic targets. PMID- 26808999 TI - Evidence for enhanced optical properties through plasmon resonance energy transfer in silver silica nanocomposites. AB - Silver nanoparticles were dispersed in the pores of monolithic mesoporous silica prepared by a modified sol-gel method. Structural and microstructural analyses were carried out by Fourier transform infrared spectroscopy and transmission electron microscopy. X-ray photoelectron spectroscopy was employed to determine the chemical states of silver in the silica matrix. Optical absorption studies show the evolution absorption band around 300 nm for silver (Ag) in a silica matrix and it was found to be redshifted to 422 nm on annealing. Photoluminescence studies indicate the presence of various luminescent emitting centers corresponding to silver ions and silver dimers in the SiO2 matrix. The enhancement of absorption and photoluminescence properties is attributed to plasmon resonance energy transfer from Ag nanoparticles to luminescent species in the matrix. PMID- 26808998 TI - Siblings Promote a Type 1/Type 17-oriented immune response in the airways of asymptomatic neonates. AB - BACKGROUND: Siblings have been shown to reduce the risk of childhood asthma and allergy, but the mechanism driving this association is unknown. The objective was to study whether siblings affect the airway immune response in healthy neonates, which could represent an underlying immune modulatory pathway. METHODS: We measured 20 immune mediators related to the Type 1, Type 2, Type 17, or regulatory immune pathways in the airway mucosa of 571 one-month-old asymptomatic neonates from the Copenhagen Prospective Studies on Asthma in Childhood2010 birth cohort (COPSAC2010 ). The association between airway mediator levels and presence of siblings was investigated using conventional statistics and principle component analysis (PCA). RESULTS: Neonates with siblings had an upregulated level of airway immune mediators, with predominance of Type 1- and Type 17 related mediators. This was supported by the PCA showing a highly significant difference between children with vs without siblings: P < 10(-10) , which persisted after adjustment for potential confounders including pathogenic airway bacteria and viruses: P < 0.0001. The immune priming effect was inversely associated with time since last childbirth: P = 0.0015. CONCLUSIONS: Siblings mediate a Type 1/Type 17-related immune-stimulatory effect in the airways of asymptomatic neonates, also after adjustment for pathogenic bacteria and viruses, indicating that siblings exert a transferable early immune modulatory effect. These findings may represent an in utero immune priming effect of the fetal immune system caused by previous pregnancies as the effect was attenuated with time since last childbirth, or it could relate to the presence of unidentified microbes, but further studies are needed to confirm our findings. PMID- 26809000 TI - Evaluation of Electroencephalography Source Localization Algorithms with Multiple Cortical Sources. AB - BACKGROUND: Source localization algorithms often show multiple active cortical areas as the source of electroencephalography (EEG). Yet, there is little data quantifying the accuracy of these results. In this paper, the performance of current source density source localization algorithms for the detection of multiple cortical sources of EEG data has been characterized. METHODS: EEG data were generated by simulating multiple cortical sources (2-4) with the same strength or two sources with relative strength ratios of 1:1 to 4:1, and adding noise. These data were used to reconstruct the cortical sources using current source density (CSD) algorithms: sLORETA, MNLS, and LORETA using a p-norm with p equal to 1, 1.5 and 2. Precision (percentage of the reconstructed activity corresponding to simulated activity) and Recall (percentage of the simulated sources reconstructed) of each of the CSD algorithms were calculated. RESULTS: While sLORETA has the best performance when only one source is present, when two or more sources are present LORETA with p equal to 1.5 performs better. When the relative strength of one of the sources is decreased, all algorithms have more difficulty reconstructing that source. However, LORETA 1.5 continues to outperform other algorithms. If only the strongest source is of interest sLORETA is recommended, while LORETA with p equal to 1.5 is recommended if two or more of the cortical sources are of interest. These results provide guidance for choosing a CSD algorithm to locate multiple cortical sources of EEG and for interpreting the results of these algorithms. PMID- 26809001 TI - Performance of two updated blood glucose monitoring systems: an evaluation following ISO 15197:2013. AB - Objective For patients with diabetes, regular self-monitoring of blood glucose (SMBG) is essential to ensure adequate glycemic control. Therefore, accurate and reliable blood glucose measurements with SMBG systems are necessary. The international standard ISO 15197 describes requirements for SMBG systems, such as limits within which 95% of glucose results have to fall to reach acceptable system accuracy. The 2013 version of this standard sets higher demands, especially regarding system accuracy, than the currently still valid edition. ISO 15197 can be applied by manufacturers to receive a CE mark for their system. Research design and methods This study was an accuracy evaluation following ISO 15197:2013 section 6.3 of two recently updated SMBG systems (Contour * and Contour TS; Bayer Consumer Care AG, Basel, Switzerland) with an improved algorithm to investigate whether the systems fulfill the requirements of the new standard. For this purpose, capillary blood samples of approximately 100 participants were measured with three test strip lots of both systems and deviations from glucose values obtained with a hexokinase-based comparison method (Cobas Integra ? 400 plus; Roche Instrument Center, Rotkreuz, Switzerland) were determined. Percentages of values within the acceptance criteria of ISO 15197:2013 were calculated. This study was registered at clinicaltrials.gov (NCT02358408). Main outcome Both updated systems fulfilled the system accuracy requirements of ISO 15197:2013 as 98.5% to 100% of the results were within the stipulated limits. Furthermore, all results were within the clinically non critical zones A and B of the consensus error grid for type 1 diabetes. Conclusions The technical improvement of the systems ensured compliance with ISO 15197 in the hands of healthcare professionals even in its more stringent 2013 version. Alternative presentation of system accuracy results in radar plots provides additional information with certain advantages. In addition, the surveillance error grid offers a modern tool to assess a system's clinical performance. PMID- 26809002 TI - Corrigendum: 3D Study of the Morphology and Dynamics of Zeolite Nucleation. PMID- 26809003 TI - Spotlights on our sister journals: Chem. Eur. J. 6/2016. PMID- 26809005 TI - Engineering nanolayered particles for modular drug delivery. AB - Layer-by-layer (LbL) based self-assembly of nanoparticles is an emerging and powerful method to develop multifunctional and tissue responsive nanomedicines for a broad range of diseases. This unique assembly technique is able to confer a high degree of modularity, versatility, and compositional heterogeneity to nanoparticles via the sequential deposition of alternately charged polyelectrolytes onto a colloidal template. LbL assembly can provide added functionality by directly incorporating a range of functional materials within the multilayers including nucleic acids, synthetic polymers, polypeptides, polysaccharides, and functional proteins. These materials can be used to generate hierarchically complex, heterogeneous thin films on an extensive range of both traditional and novel nanoscale colloidal templates, providing the opportunity to engineer highly precise systems capable of performing the numerous tasks required for systemic drug delivery. In this review, we will discuss the recent advancements towards the development of LbL nanoparticles for drug delivery and diagnostic applications, with a special emphasis on the incorporation of biostability, active targeting, desirable drug release kinetics, and combination therapies into LbL nanomaterials. In addition to these topics, we will touch upon the next steps for the translation of these systems towards the clinic. PMID- 26809004 TI - Translocation of LRP1 targeted carbon nanotubes of different diameters across the blood-brain barrier in vitro and in vivo. AB - Brain glioblastoma and neurodegenerative diseases are still largely untreated due to the inability of most drugs to cross the blood-brain barrier (BBB). Nanoparticles have emerged as promising tools for drug delivery applications to the brain; in particular carbon nanotubes (CNTs) that have shown an intrinsic ability to cross the BBB in vitro and in vivo. Angiopep-2 (ANG), a ligand for the low-density lipoprotein receptor-related protein-1 (LRP1), has also shown promising results as a targeting ligand for brain delivery using nanoparticles (NPs). Here, we investigate the ability of ANG-targeted chemically-functionalised multi-walled carbon nanotubes (f-MWNTs) to cross the BBB in vitro and in vivo. ANG was conjugated to wide and thin f-MWNTs creating w-MWNT-ANG and t-MWNT-ANG, respectively. All f-MWNTs were radiolabelled to facilitate quantitative analyses by gamma-scintigraphy. ANG conjugation to f-MWNTs enhanced BBB transport of w- and t-MWNTs-ANG compared to their non-targeted equivalents using an in vitro co cultured BBB model consisting of primary porcine brain endothelial cells (PBEC) and primary rat astrocytes. Additionally, following intravenous administration w MWNTs-ANG showed significantly higher whole brain uptake than the non-targeted w MWNT in vivo reaching ~2% injected dose per g of brain (%ID/g) within the first hour post-injection. Furthermore, using a syngeneic glioma model, w-MWNT-ANG showed enhanced uptake in glioma brain compared to normal brain at 24h post injection. t-MWNTs-ANG, on the other hand, showed higher brain accumulation than w-MWNTs. However, no significant differences were observed between t-MWNT and t MWNT-ANG indicating the importance of f-MWNTs diameter towards their brain accumulation. The inherent brain accumulation ability of f-MWNTs coupled with improved brain-targeting by ANG favours the future clinical applications of f MWNT-ANG to deliver active therapeutics for brain glioma therapy. PMID- 26809006 TI - Slow release coating remedy for nitrogen loss from conventional urea: a review. AB - Developing countries are consuming major part of the global urea production with an anticipated nitrogen use efficiency of 20 to 35%. The release of excess nitrogen in the soil is not only detrimental to the environment but also lessens the efficiency of the conventional urea. The urea performance can be enhanced by encapsulating it with slow release coating materials and synchronizing the nutrients' release with the plant up-taking. However, the present cost of most of the coated fertilizers is considerably higher than the conventional fertilizers. The high cost factor prevents their widespread use in mainstream agriculture. This paper documents a review of literature related to the global urea market, issues pertaining to the conventional urea use, natural and synthetic materials for slow release urea and fluidized bed spray coating process. The aim of the current review is to develop technical understanding of the conventional and non conventional coating materials and associated spray coating mechanism for slow release urea production. The study also investigated the potential of starch as the coating material in relation to the coatings tested previously for controlled release fertilizers. PMID- 26809007 TI - Targeting of pegylated liposomal mitomycin-C prodrug to the folate receptor of cancer cells: Intracellular activation and enhanced cytotoxicity. AB - Mitomycin C (MMC) is a powerful anti-bacterial, anti-fungal and anti-tumor antibiotic, often active against multidrug resistant cells. Despite a broad spectrum of antitumor activity, MMC clinical use is relatively limited due to its fast clearance and dose-limiting toxicity. To exploit the potential antitumor activity of MMC and reduce its toxicity we have previously developed a formulation of pegylated liposomes with a lipophilic prodrug of MMC (PL-MLP), activated by endogenous reducing agents which are abundant in the tumor cell environment in the form of different thiols. PL-MLP has minimal in vitro cytotoxicity unless reducing agents are added to the cell culture to activate the prodrug. In the present study, we hypothesized that targeting PL-MLP via folate receptors will facilitate intracellular activation of prodrug and enhance cytotoxic activity without added reducing agents. We grafted a lipophilic folate conjugate (folate-PEG(5000)-DSPE) to formulate folate targeted liposomes (FT-PL MLP) and examined in vitro cell uptake and cytotoxic activity in cancer cell lines with high folate receptors (HiFR). 3H-cholesterol-hexadecyl ether (3H-Chol) radiolabeled liposomes were prepared to study liposome-cell binding in parallel to cellular uptake of prodrug MLP. 3H-Chol and MLP cell uptake levels were 4-fold and 9-fold greater in KB HiFR cells when FT-PL-MLP is compared to non-targeted PL MLP liposomes. The cytotoxic activity of FT-PL-MLP liposomes was significantly increased up to ~5-fold compared with PL-MLP liposomes in all tested HiFR expressing cell lines. The enhanced uptake and intracytoplasmic liposome delivery was confirmed by confocal fluorescence studies with Rhodamine-labeled liposomes. In vivo, no significant differences in pharmacokinetics and biodistribution were observed when PL-MLP was compared to FT-PL-MLP by the intravenous route. However, when liposomes were directly injected into the peritoneal cavity of mice with malignant ascites of J6456 HiFR lymphoma cells, the tumor cell levels of MLP were significantly greater with the folate-targeted liposomes. Thus, folate targeting enhances liposome uptake by tumor cells enabling intracellular activation of prodrug in the absence of exogenous reducing agents, and leading to increased cytotoxicity. These results may be particularly relevant to the application of folate-targeted PL-MLP in intracavitary or intravesical treatment of cancer. PMID- 26809008 TI - Potential Immunomodulatory Effects of Statins in Inflammatory Bowel Disease. AB - Statins are among the most widely prescribed medications in the world. In addition to lowering cholesterol, statins have been shown to have immunomodulatory effects in multiple studies. For example, statins modulate the interaction between T cells and antigen-presenting cells, resulting in decreased T-cell activation and reduced levels of inflammatory cytokines. Statins have also been demonstrated to inhibit the migration of leukocytes across vascular endothelium into tissues. Although most research on the immune effects of statins has been conducted in the context of cardiovascular, rheumatological, or metabolic disease, various studies have shown that statins may have a significant impact on intestinal immunity and mucosal inflammation. Clinical research has suggested that statins may have benefit in inflammatory bowel disease. In this article, we review the effect of statins on the immune system and gastrointestinal tract, highlighting the potential for novel therapeutic applications in inflammatory bowel disease. PMID- 26809009 TI - Subjects with Knee Osteoarthritis Exhibit Widespread Hyperalgesia to Pressure and Cold. AB - Hyperalgesia to mechanical and thermal stimuli are characteristics of a range of disorders such as tennis elbow, whiplash and fibromyalgia. This study evaluated the presence of local and widespread mechanical and thermal hyperalgesia in individuals with knee osteoarthritis, compared to healthy control subjects. Twenty-three subjects with knee osteoarthritis and 23 healthy controls, matched for age, gender and body mass index, were recruited for the study. Volunteers with any additional chronic pain conditions were excluded. Pain thresholds to pressure, cold and heat were tested at the knee, ipsilateral heel and ipsilateral elbow, in randomized order, using standardised methodology. Significant between groups differences for pressure pain and cold pain thresholds were found with osteoarthritic subjects demonstrating significantly increased sensitivity to both pressure (p = .018) and cold (p = .003) stimuli, compared with controls. A similar pattern of results extended to the pain-free ipsilateral ankle and elbow indicating widespread pressure and cold hyperalgesia. No significant differences were found between groups for heat pain threshold, although correlations showed that subjects with greater sensitivity to pressure pain were also likely to be more sensitive to both cold pain and heat pain. This study found widespread elevated pain thresholds in subjects with painful knee osteoarthritis, suggesting that altered nociceptive system processing may play a role in ongoing arthritic pain for some patients. PMID- 26809010 TI - Accuracy of Non-Enhanced CT in Detecting Early Ischemic Edema Using Frequency Selective Non-Linear Blending. AB - PURPOSE: Ischemic brain edema is subtle and hard to detect by computed tomography within the first hours of stroke onset. We hypothesize that non-enhanced CT (NECT) post-processing with frequency-selective non-linear blending ("best contrast"/BC) increases its accuracy in detecting edema and irreversible tissue damage (infarction). METHODS: We retrospectively analyzed the NECT scans of 76 consecutive patients with ischemic stroke (exclusively middle cerebral artery territory-MCA) before and after post-processing with BC both at baseline before reperfusion therapy and at follow-up (5.73+/-12.74 days after stroke onset) using the Alberta Stroke Program Early CT Score (ASPECTS). We assessed the differences in ASPECTS between unprocessed and post-processed images and calculated sensitivity, specificity, and predictive values of baseline NECT using follow-up CT serving as reference standard for brain infarction. RESULTS: NECT detected brain tissue hypoattenuation in 35 of 76 patients (46.1%). This number increased to 71 patients (93.4%) after post-processing with BC. Follow-up NECT confirmed brain infarctions in 65 patients (85.5%; p = 0.012). Post-processing increased the sensitivity of NECT for brain infarction from 35/65 (54%) to 65/65 (100%), decreased its specificity from 11/11 (100%) to 7/11 (64%), its positive predictive value (PPV) from 35/35 (100%) to 65/69 (94%) and increased its accuracy 46/76 (61%) to 72/76 (95%). CONCLUSIONS: This post-hoc analysis suggests that post-processing of NECT with BC may increase its sensitivity for ischemic brain damage significantly. PMID- 26809011 TI - Treat-to-target in systemic lupus erythematosus: are we there yet? AB - The treat-to-target (T2T) strategy has proven benefits in several chronic medical illnesses including rheumatoid arthritis. Whether the T2T principle can be applied to SLE has become a recent topic of discussion. A European panel of rheumatologists agrees that treatment of SLE should target at multiple goals that include control of disease activity, prevention of disease flares, minimization of disease or treatment related comorbidity, and improvement of quality of life. Therapy of SLE should aim at remission or when remission cannot be achieved, the lowest possible disease activity that is assessed by a validated lupus activity index and/or organ-specific markers. However, owing to the clinical heterogeneity of SLE, there is still no consensus on the definition of remission or low disease activity state in individual organ-systems. In real life, agents readily available for therapy switching in SLE are limited. Moreover, no disease activity index is universally agreed upon for disease monitoring to make therapeutic decisions. Currently, clinical parameters for the assessment and monitoring of lupus renal disease appear to be more objective and evidence-based. A therapeutic target in terms of proteinuria and/or other renal parameters should be tested in randomized controlled trials for the proof of the T2T concept in SLE. PMID- 26809012 TI - Being Two Is Better than Being One: A Facile Strategy to Fabricate Multicomponent Nanoparticles for Efficient Gene Delivery. AB - Multifunctionality is necessary in the design of efficient gene vectors due to the existence of multiple barriers during gene delivery. Traditional methods in the design of polyfunctional materials for this purpose are associated with sophisticated syntheses and high costs. Here, we proposed a facile coassembly approach to fabricate multicomponent nanoparticles for efficient gene delivery. The resulting particles contain different functional dendrimers and show favorable physicochemical characteristics. All the combinations in the fabrication of multicomponent nanoparticles show a synergistic effect in improving transfection efficacy. The prepared nanoparticles successfully address two or more barriers in the gene delivery process and show minimal toxicity on the transfected cells. The combination of high transfection efficacy and low cytotoxicity suggests that the prepared multicomponent nanoparticles as promising carriers in gene delivery. PMID- 26809013 TI - Low Incidence of Synchronous or Metachronous Tumors after Endoscopic Submucosal Dissection for Early Gastric Cancer with Undifferentiated Histology. AB - BACKGROUND: Gastric cancer with undifferentiated histology has different clinicopathologic characteristics compared to differentiated type gastric cancer. We aimed to compare the risk of synchronous or metachronous tumors after curative resection of early gastric cancer (EGC) via endoscopic submucosal dissection (ESD), according to the histologic differentiation of the primary lesion. METHODS: Clinicopathological data of patients with initial-onset EGC curatively resected via ESD between January 2007 and November 2014 in a single institution were reviewed. We analyzed the incidence of synchronous or metachronous tumors after ESD with special reference to the differentiation status of the primary lesion. RESULTS: Of 1,560 patients with EGC who underwent curative resection via ESD, 1,447 had differentiated type cancers, and 113 had undifferentiated type cancers. The cumulative incidence of metachronous or synchronous tumor after ESD was higher in the differentiated cancer group than in the undifferentiated cancer group (P = 0.008). Incidence of metachronous or synchronous tumor was 4.8% and 1.2% per person-year in the differentiated and undifferentiated cancer groups, respectively. The Cox proportional hazard model revealed that undifferentiated cancers were associated with a low risk of synchronous or metachronous tumors after adjusting for confounding variables (hazard ratio [95% confidence interval] = 0.287 [0.090-0.918]). CONCLUSIONS: The rate of synchronous or metachronous tumors after curative ESD was significantly lower for undifferentiated cancers compare to differentiated cancers. These findings suggest that ESD should be actively considered as a possible treatment for undifferentiated type EGCs. PMID- 26809014 TI - Adjuvant therapy for nonsmall cell lung cancer: recent advances and future perspectives. AB - PURPOSE OF REVIEW: In this article, we discuss the emergence of adjuvant chemotherapy as the standard of care, the potential role of targeted and immune therapy in resected nonsmall cell lung cancer (NSCLC) patients, and the importance of ongoing clinical trials to further define the use of these agents as adjuvant therapy. RECENT FINDINGS: Adjuvant chemotherapy after surgical resection provides modest improvements in cure rate, though recurrence of disease still occurs in a substantial proportion of patients. The advent of targeted and immune therapies has improved outcomes for patients with advanced stage NSCLC. Recent studies have explored the role of vascular endothelial growth factor inhibitors, epidermal growth factor receptor tyrosine kinase inhibitors, vaccine therapy, and predictive biomarkers in the adjuvant setting. SUMMARY: Platinum doublet chemotherapy remains the standard adjuvant therapy for resected stage II, IIIA, and high-risk stage IB NSCLC. Ongoing clinical trials are evaluating emerging therapies to improve efficacy and reduce toxicity while aiming to improve patient selection for such therapies. PMID- 26809015 TI - Treatment of melanoma brain metastases. AB - PURPOSE OF REVIEW: Melanoma has a tendency to metastasize to the brain. The development of brain metastasis is observed in all mutational subgroups. Overall, they are associated with poor prognosis. They are also associated with pain, neurological deterioration and thus, have a major impact on patients' quality of life. Historically, effective palliation by systemic therapy has been rare. The availability of new therapeutic agents, however, heralds a significant improvement in management options for these patients. RECENT FINDINGS: The development of targeted therapies and immune activating checkpoint inhibitors with durable benefit has led to a treatment paradigm change. Several clinical studies in patients with metastatic melanoma have demonstrated improved survival compared to chemotherapy. Many of these studies however excluded patients with brain involvement. Antitumor activity in brain metastasis has now been observed with some agents; further positive data are emerging. Surgery and stereotactic radiotherapy are also used for local control of oligometastatic disease. We discuss the usefulness of the available systemic treatments for management of brain metastases and how these are integrated with local treatments to enable optimal palliation. SUMMARY: Advances in the treatment of melanoma are providing significant palliative benefit for patients with brain metastases. Further investigations are needed to determine optimal treatment combinations and sequences. PMID- 26809016 TI - Camelid antivenom development and potential in vivo neutralization of Hottentotta saulcyi scorpion venom. AB - Scorpion envenoming is a serious health problem which can cause a variety of clinical toxic effects. Of the many scorpion species native to Iran, Hottentotta saulcyi is important because its venom can produce toxic effects in man. Nowadays, antivenom derived from hyper immune horses is the only effective treatment for sever scorpion stings. Current limitations of immunotherapy urgently require an efficient alternative with high safety, target affinity and more promising venom neutralizing capability. Recently, heavy chain-only antibodies (HC-Abs) found naturally in camelid serum met the above mentioned advantages. In this study, immuno-reactivities of polyclonal antibodies were tested after successful immunization of camel using H. saulcyi scorpion crude venom. The lethal potency of scorpion venom in C57BL/6 mice injected intraperitoneally was determined to be 2.7 mg/kg. These results were followed by the efficient neutralization of lethal activity of H. saulcyi scorpion venom by injection of antivenom and purified IgG fractions into mice intraperitonelly or intravenously, respectively. HC-Ab camelid antivenom could be considered as a useful serotherapeutics instead of present treatment for scorpion envenomation. PMID- 26809017 TI - Stacking dependence of carrier transport properties in multilayered black phosphorous. AB - We present the effect of different stacking orders on carrier transport properties of multi-layer black phosphorous. We consider three different stacking orders AAA, ABA and ACA, with increasing number of layers (from 2 to 6 layers). We employ a hierarchical approach in density functional theory (DFT), with structural simulations performed with generalized gradient approximation (GGA) and the bandstructure, carrier effective masses and optical properties evaluated with the meta-generalized gradient approximation (MGGA). The carrier transmission in the various black phosphorous sheets was carried out with the non-equilibrium green's function (NEGF) approach. The results show that ACA stacking has the highest electron and hole transmission probabilities. The results show tunability for a wide range of band-gaps, carrier effective masses and transmission with a great promise for lattice engineering (stacking order and layers) in black phosphorous. PMID- 26809018 TI - Hypertensive disorders first identified in pregnancy increase risk for incident prehypertension and hypertension in the year after delivery. AB - BACKGROUND: Hypertensive disorders in pregnancy, including preeclampsia/eclampsia (PE/E) are associated with long-term cardiovascular disease risk. However, little is known about the effect of these conditions on risk for prehypertension (preHTN) or hypertension (HTN) in the early years after delivery. METHODS: The cohort consisted of women who had prenatal care and delivered a live singleton neonate at Kaiser Permanente Bellflower Medical Center in 2005-2010. Women with prepregnancy HTN or preHTN were excluded from analysis. Multivariable robust Poisson regression models were used to assess associations between any hypertensive disorder or PE/E and development of preHTN/HTN in the year after delivery, adjusted for maternal age, race/ethnicity, parity, smoking, prepregnancy weight status, gestational weight gain, gestational diabetes, and gestational age. RESULTS: Among 5960 women who were normotensive prior to pregnancy, 358 (6.0%) developed a hypertensive disorder in pregnancy, of whom 215 (60.1%) had PE/E. Overall, 63 (1.1%) developed HTN and 902 (15.1%) preHTN in the year after delivery. After accounting for all potential confounders, women with a hypertensive disorder in pregnancy and those with PE/E were 2.36 (95% confidence interval: 1.97-2.83) and 2.48 (95% confidence interval: 1.99-3.11) times as likely, respectively, to develop preHTN/HTN in the year after delivery as those without pregnancy-related HTN. Results were similar with and without adjustment for gestational diabetes. CONCLUSION: Our findings highlight the need for prospective studies aimed at determining whether early postpartum screening and improved follow-up of women with hypertensive disorders first identified in pregnancy may prevent future cardiovascular disease. PMID- 26809019 TI - Complete excision of a posterior mediastinal goitre causing tracheal deviation. PMID- 26809020 TI - Overweight parents are twice as likely to underestimate the weight of their teenage children, regardless of their sociodemographic characteristics. AB - AIM: It is unclear whether parents' weight affects their ability to recognise whether their teenage children are overweight. This study analysed whether overweight parents assessed their child's weight as well as normal weight parents. METHODS: This cross-sectional study was carried out in Londrina, Brazil, in 2011 and included teenagers between 14 and 17 years of age and their parents or guardians. We recorded the weight and height of the teenagers and asked the parents or guardians to fill in a questionnaire that included how they perceived their child's weight and demographic information. RESULTS: We studied 1231 teenagers - 58.2% girls - and 19.4% were overweight or obese. In 842 (68.4%) of cases both parents replied to the questionnaire. We found that 8.7% of the 1202 mothers and 10.0% of the 871 fathers underestimated how overweight their child was. The adjusted analyses confirmed they were twice as likely to underestimate their child's weight if they were overweight themselves, with an odds ratio of 1.96 for the mothers and 2.04 for the fathers. Sociodemographic characteristics did not affect the results. CONCLUSION: Overweight parents were twice as likely to underestimate the weight of their teenage children, regardless of the sociodemographic characteristics. PMID- 26809021 TI - Disentangling canid howls across multiple species and subspecies: Structure in a complex communication channel. AB - Wolves, coyotes, and other canids are members of a diverse genus of top predators of considerable conservation and management interest. Canid howls are long-range communication signals, used both for territorial defence and group cohesion. Previous studies have shown that howls can encode individual and group identity. However, no comprehensive study has investigated the nature of variation in canid howls across the wide range of species. We analysed a database of over 2000 howls recorded from 13 different canid species and subspecies. We applied a quantitative similarity measure to compare the modulation pattern in howls from different populations, and then applied an unsupervised clustering algorithm to group the howls into natural units of distinct howl types. We found that different species and subspecies showed markedly different use of howl types, indicating that howl modulation is not arbitrary, but can be used to distinguish one population from another. We give an example of the conservation importance of these findings by comparing the howls of the critically endangered red wolves to those of sympatric coyotes Canis latrans, with whom red wolves may hybridise, potentially compromising reintroduced red wolf populations. We believe that quantitative cross-species comparisons such as these can provide important understanding of the nature and use of communication in socially cooperative species, as well as support conservation and management of wolf populations. PMID- 26809022 TI - Hybrid Therapy as First-Line Regimen for Helicobacter pylori Eradication in Populations with High Antibiotic Resistance Rates. AB - BACKGROUND: Hybrid therapy has recently attracted widespread attention. However, many issues require further exploration. For example, research in regions with high antibiotic resistance rates is limited, and the correlation between eradication efficacy and antibiotic resistance remains unclear. The aim of this study was to determine the efficacy, compliance, safety, and risk factors of hybrid therapy as first-line regimen in a region with high antibiotic resistance rates. MATERIALS AND METHODS: This prospective study was conducted in a tertiary hospital between January 2014 and June 2015. A total of 196 patients with dyspepsia but without prior eradication therapy received hybrid regimen (esomeprazole 20 mg and amoxicillin 1000 mg twice daily for 14 days with the addition of clarithromycin 500 mg and tinidazole 500 mg twice daily for the final 7 days). All patients underwent Helicobacter pylori culture, antibiotic susceptibility testing and cytochrome P450 isoenzyme 2C19 polymorphism testing. RESULTS: Hybrid therapy achieved eradication rates of 77.0% (95% confidence interval (CI), 70.9-83.7%) in intention-to-treat (ITT), 83.9% (78.9-88.9%) in modified ITT and 86.0% (80.2-91.3%) in per-protocol analyses in a setting with high antibiotic resistance rates (amoxicillin 2.0%, clarithromycin 44.9%, metronidazole 67.3% and dual clarithromycin and metronidazole 33.3%). Adverse reactions occurred in 31.9% patients and 2.7% discontinued medications due to adverse reactions. Good compliance was achieved by 92.0%. Multivariate analyses identified clarithromycin resistance (odds ratio, 3.494; 95% CI, 1.237-9.869), metronidazole resistance (3.012; 1.013-12.054) and poor compliance (5.840; 1.126 30.296) as independent predictors of treatment failure. The eradication rate with dual clarithromycin and metronidazole resistance (70.2%) was markedly decreased compared to isolated clarithromycin resistance (87.5%), isolated metronidazole resistance (88.6%), or dual susceptibility (96.4%) (p = .014). CONCLUSIONS: Despite good compliance and safety, hybrid therapy as first-line regimen in populations with high antibiotic resistance rates had unsatisfactory efficacy, primarily due to dual clarithromycin and metronidazole resistance. PMID- 26809023 TI - Perspectives in Pediatric Pathology, Chapter 17. Other Hypergonadotropic Hypogonadisms. PMID- 26809024 TI - Novel immunotherapeutic strategies in chronic inflammatory demyelinating polyneuropathy. AB - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic immune-mediated neuropathy: it is clinically heterogeneous (relapsing-remitting form, chronic progressive form, monophasic form or CIDP having a Guillain-Barre syndrome-like onset), but potentially treatable. Although its pathophysiology remains largely unknown, CIDP is considered an immune-mediated neuropathy. Therefore, many immunotherapies have been proposed in this peripheral nervous system disorder, the most known efficient treatments being intravenous immunoglobulin, corticosteroids and plasma exchange. However, these therapies remain unsatisfactory for many patients, so numerous other immunotherapeutic strategies have been evaluated, based on their immunosuppressant or immunomodulatory potency. We have performed a large review of the literature about treatment in CIDP, with a special emphasis on novel and alternative immunotherapeutic strategies. PMID- 26809025 TI - Atomistic resolution structure and dynamics of lipid bilayers in simulations and experiments. AB - Accurate details on the sampled atomistic resolution structures of lipid bilayers can be experimentally obtained by measuring C-H bond order parameters, spin relaxation rates and scattering form factors. These parameters can be also directly calculated from the classical atomistic resolution molecular dynamics simulations (MD) and compared to the experimentally achieved results. This comparison measures the simulation model quality with respect to 'reality'. If agreement is sufficient, the simulation model gives an atomistic structural interpretation of the acquired experimental data. Significant advance of MD models is made by jointly interpreting different experiments using the same structural model. Here we focus on phosphatidylcholine lipid bilayers, which out of all model membranes have been studied mostly by experiments and simulations, leading to the largest available dataset. From the applied comparisons we conclude that the acyl chain region structure and rotational dynamics are generally well described in simulation models. Also changes with temperature, dehydration and cholesterol concentration are qualitatively correctly reproduced. However, the quality of the underlying atomistic resolution structural changes is uncertain. Even worse, when focusing on the lipid bilayer properties at the interfacial region, e.g. glycerol backbone and choline structures, and cation binding, many simulation models produce an inaccurate description of experimental data. Thus extreme care must be applied when simulations are applied to understand phenomena where the interfacial region plays a significant role. This work is done by the NMRlipids Open Collaboration project running at https://nmrlipids.blogspot.fi and https://github.com/NMRLipids. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Rog. PMID- 26809026 TI - Complete response in a critically ill patient with ALK-negative anaplastic large cell lymphoma treated with single agent brentuximab-vedotin. AB - Anaplastic large cell lymphoma (ALCL) is a rare hematological malignancy and a distinct subtype of mature T-cell lymphomas. ALCL is comprised of two clinically distinct but morphologically similar sub-class under 2008 WHO classification: cutaneous and systemic. Primary systemic ALCL is further sub-categorized into tumors that carry the anaplastic lymphoma kinase (ALK) gene rearrangement or not; ALK-positive versus ALK-negative disease respectively. Traditionally, both forms of primary systemic ALCL have been treated upfront with an anthracycline based combination chemotherapy such as CHOP. More recently an antibody drug conjugate, brentuximab-vedotin (BV), directed against CD30 antigen has shown promise in CD30 expressing hematologic malignancies such as Hodgkin's lymphoma and ALCL. At the present time, this novel antibody-drug conjugate has been approved in the treatment of patients with ALCL after failure of at least one prior multi-agent chemotherapy regimen in the United States. We present a case describing a previously healthy 48 year-old female diagnosed with ALK-negative ALCL who achieved complete response with upfront single agent brentuximab-vedotin. It is the first case described in the literature utilizing BV in the first line setting particularly in a patient with multi-organ failure and critically ill at time of diagnosis. This case highlights the full potential that targeted therapies can exert over hematological malignancies while also minimizing treatment related toxicities. ABBREVIATIONS: AE: adverse event; ALCL: anaplastic large cell lymphoma; ALK: anaplastic lymphoma kinase; ASCT: autologous stem cell transplant; BEAM: BCNU/carmustine, etoposide, ara-C, and melphalan; BV: brentuximab vedotin; CHEOP: cyclophosphamide, daunorubicin, vincristine, prednisone, etoposide; CHOP: cyclophosphamide, doxorubicin, vincristine, prednisone; CR:complete response; G3+: grade 3 or higher; MTD: maximum tolerated dose; ORR: overall response rate; OS: overall survival; PFS: progression-free survival. PMID- 26809027 TI - Bioassay-guided isolation and evaluation of antimicrobial compounds from Ixora megalophylla against some oral pathogens. AB - Context Ixora megalophylla Chamch. (Rubiaceae) is a new plant species recently found in southern Thailand. Ethyl acetate extracts of its leaves and stems showed antimicrobial activities. Objectives To isolate and identify the antimicrobial compounds from I. megalophylla leaves and stems. Materials and methods The dried leaves (1.7 kg) and stems (3.5 kg) were consecutively extracted with petroleum ether (5 L * 4), ethyl acetate (5 L * 3) and ethanol (5 L * 4) under reflux conditions. The ethyl acetate extract was subjected to an antimicrobial assay guided isolation with Candida albicans and Streptococcus mutans. Compounds 1-10 were identified by (1)H NMR, (13)C NMR and EI-MS. Minimal lethal concentration (MLC) against C. albicans and Streptococcus spp. was determined using a broth microdilution method for 48 and 24 h, respectively. Results and discussion On the basis of the antimicrobial assay guided isolation, 10 known compounds, including vanillic acid (1), syringic acid (2), 4-hydroxy benzaldehyde (3), scopoletin (4), loliolide (5), syringaldehyde (6), sinapaldehyde (7), coniferaldehyde (8), syringaresinol (9) and 2,2'-dithiodipyridine (10), were identified. Compounds 1-5 were purified from the ethyl acetate extract of the leaves, while 6-9 and 10 were from the ethyl acetate and ethanol extracts of the stems, respectively. Among these isolates, 10 showed the strongest antibacterial activities against S. mutans and Streptococcus mitis, with minimum inhibitory concentrations (MICs) of 2-4 MUg/mL, and MLC of 4 MUg/mL, as well as having a weak antifungal activity against C. albicans (MIC of 125 MUg/mL). This is the first report of the antimicrobial activities of 10. PMID- 26809028 TI - Safety of treatments for primary Sjogren's syndrome. AB - INTRODUCTION: Primary Sjogren's syndrome (pSS) is a disabling auto-immune disease, affecting exocrine glands and several organs. AREAS COVERED: In this review we analyze the safety of therapies used in pSS. Symptomatic treatment is widely applied due to the good supportive effect and good safety profile. Systemic stimulation of tears and saliva can be successful in pSS. However, cumbersome adverse events can influence the tolerability of this therapy. Evidence for the effectiveness of synthetic DMARDs therapies in pSS is limited, while there is a risk of adverse events. Several studies on biologic DMARD treatment of pSS patients have shown promising efficacy and safety results. EXPERT OPINION: The safety of symptomatic treatment of pSS is very good. However, systemic therapy is necessary to achieve long-term relieve and prevention of organ-damage. Synthetic DMARDs have not shown much efficacy in earlier studies, and their benefits do not weigh up to the possible harms, while biologic DMARDs show promising results regarding efficacy and cause mostly mild adverse events. Many questions remain unanswered regarding safety of DMARDs in pSS. There is a need for well designed studies, in which safety should be evaluated in a uniform manner to be able to compare the results between studies. PMID- 26809029 TI - Family Caregivers Who Would Be Unwilling to Provide Care at the End of Life Again: Findings from the Health Survey for England Population Survey. AB - BACKGROUND: Family caregivers provide significant care at the end of life. We aimed to describe caregiver characteristics, and of those unwilling to repeat this role under the same circumstances. METHODS: Observational study of adults in private households (Health Survey for England [HSE]). Caregiving questions included: whether someone close to them died within past 5 years; relationship to the deceased; provision, intensity and duration of care; supportive/palliative care services used; willingness to care again; able to carry on with life. Comparison between those willing to care again or not used univariable analyses and an exploratory multiple logistic regression. A descriptive comparison with Health Omnibus Survey (Australia) data was conducted. FINDINGS: HSE response was 64%. 2167/8861 (25%) respondents had someone close to them die in the previous 5 years. Some level of personal care was provided by 645/8861 (7.3%). 57/632 (9%) former caregivers would be unwilling to provide care again irrespective of time since the death, duration of care, education and income. Younger age (<=65; odds ratio [OR] 2.79; 95% CI 136, 5.74) and use of palliative care services (odds ratio: 1.95, 95% CI: 1.09, 3.48) showed greater willingness to provide care again. Apart from use of palliative care services, findings were remarkably similar to the Australian data. CONCLUSIONS: A significant group of caregivers would be unwilling to provide care again. Older people and those who had not used palliative care services were more likely to be unwilling to care again. Barriers preventing access for disadvantaged groups need to be overcome. PMID- 26809030 TI - Enantiopure Ferrocene-Based Planar-Chiral Iridacycles: Stereospecific Control of Iridium-Centred Chirality. AB - Reaction of [IrCp*Cl2 ]2 with ferrocenylimines (Fc=NAr, Ar=Ph, p-MeOC6 H4 ) results in ferrocene C-H activation and the diastereoselective synthesis of half sandwich iridacycles of relative configuration Sp *,RIr *. Extension to (S)-2 ferrocenyl-4-(1-methylethyl)oxazoline gave highly diastereoselective control over the new elements of planar chirality and metal-based pseudo-tetrahedral chirality, to give both neutral and cationic half-sandwich iridacycles of absolute configuration Sc ,Sp ,RIr . Substitution reactions proceed with retention of configuration, with the planar chirality controlling the metal centred chirality through an iron-iridium interaction in the coordinatively unsaturated cationic intermediate. PMID- 26809032 TI - Paradoxical Adipose Hyperplasia after Cryolipolysis: A Report on Incidence and Common Factors Identified in 510 Patients. PMID- 26809033 TI - Deaths Caused by Gluteal Lipoinjection: What Are We Doing Wrong? PMID- 26809031 TI - E2F/Rb Family Proteins Mediate Interferon Induced Repression of Adenovirus Immediate Early Transcription to Promote Persistent Viral Infection. AB - Interferons (IFNs) are cytokines that have pleiotropic effects and play important roles in innate and adaptive immunity. IFNs have broad antiviral properties and function by different mechanisms. IFNs fail to inhibit wild-type Adenovirus (Ad) replication in established cancer cell lines. In this study, we analyzed the effects of IFNs on Ad replication in normal human cells. Our data demonstrate that both IFNalpha and IFNgamma blocked wild-type Ad5 replication in primary human bronchial epithelial cells (NHBEC) and TERT-immortalized normal human diploid fibroblasts (HDF-TERT). IFNs inhibited the replication of divergent adenoviruses. The inhibition of Ad5 replication by IFNalpha and IFNgamma is the consequence of repression of transcription of the E1A immediate early gene product. Both IFNalpha and IFNgamma impede the association of the transactivator GABP with the E1A enhancer region during the early phase of infection. The repression of E1A expression by IFNs requires a conserved E2F binding site in the E1A enhancer, and IFNs increased the enrichment of the E2F-associated pocket proteins, Rb and p107, at the E1A enhancer in vivo. PD0332991 (Pabociclib), a specific CDK4/6 inhibitor, dephosphoryles pocket proteins to promote their interaction with E2Fs and inhibited wild-type Ad5 replication dependent on the conserved E2F binding site. Consistent with this result, expression of the small E1A oncoprotein, which abrogates E2F/pocket protein interactions, rescued Ad replication in the presence of IFNalpha or IFNgamma. Finally, we established a persistent Ad infection model in vitro and demonstrated that IFNgamma suppresses productive Ad replication in a manner dependent on the E2F binding site in the E1A enhancer. This is the first study that probes the molecular basis of persistent adenovirus infection and reveals a novel mechanism by which adenoviruses utilize IFN signaling to suppress lytic virus replication and to promote persistent infection. PMID- 26809034 TI - Reply: The Use of Reduction Mammaplasty with Breast Conservation Therapy: An Analysis of Timing and Outcomes. PMID- 26809035 TI - Reply: Obesity-Induced Lymphedema: Clinical and Lymphoscintigraphic Features. PMID- 26809036 TI - Evidence-Based Education in Plastic Surgery. PMID- 26809037 TI - Selective Sentinel Lymph Node Dissection in Lower Extremity Melanoma. AB - BACKGROUND: There is debate as to whether deep inguinal lymph nodes should be removed with the superficial or femoral lymph nodes during sentinel lymph node biopsy for lower extremity melanoma, when both superficial and deep inguinal lymph nodes are identified by preoperative lymphoscintigraphy. This study evaluated the lymphatic drainage patterns in lower extremity melanoma to determine whether certain patterns could be used to limit the level of node removal and define the extent of dissection. METHODS: A retrospective outcomes review was performed of lower extremity melanoma patients with excision and sentinel lymph node biopsy from 1995 to 2010. Outcomes included location of sentinel lymph node drainage basins, sentinel lymph node-positivity, and disease free and overall survival, with drainage patterns compared between above- and below-knee melanomas. RESULTS: Of 499 patients with lower extremity melanoma having sentinel lymph node biopsy, 356 had below-the-knee and 143 had above-the knee melanoma. For below-knee melanoma, the node-positivity rate was 23 percent (63 of 271) for superficial inguinal, 0 percent (zero of three) for deep inguinal, and 50 percent (one of two) for popliteal basins. For above-knee melanoma, the positivity rate was 21 percent (24 of 113) for superficial inguinal, 33 percent (one of three) for deep inguinal basins, and 0 percent (zero of zero) for popliteal basins. Importantly, no patients with a negative superficial inguinal sentinel lymph node had a positive deep inguinal sentinel lymph node on final pathologic evaluation [corrected]. CONCLUSIONS: A difference was noted in patterns of sentinel lymph node drainage from lower extremity melanoma below and above the knee. Biopsy for deep inguinal basins may be deferred if there is simultaneous drainage to the superficial inguinal basin by preoperative lymphoscintigraphy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II. PMID- 26809038 TI - Vascularized Lymph Node Transfer: A Review of the Current Evidence. AB - Over the past decade, lymph node transfer has rapidly gained popularity among plastic surgeons for the treatment of chronic lymphedema because of the initial promising results and its unique technical advantages compared with the other reconstructive options. However, its functional mechanism is still a matter of great debate, and some concerning reports have emerged regarding the safety of this procedure in patients with chronic lymphedema. The authors review the literature on the experimental and clinical evidence for lymph node transfer, discuss its proposed functional mechanisms, review the potential risk of iatrogenic lymphedema following this procedure, and discuss the suggested strategies to avoid this complication. PMID- 26809039 TI - Learner Perspectives of a Surgical Educators Faculty Development Program Regarding Value and Effectiveness: A Qualitative Study. AB - BACKGROUND: The BaylorScott & White Health Division of Plastic Surgery began a faculty development program designed to train clinicians to be better educators. The program consisted of presession reading, 11 small group didactic sessions, and individually chosen educational projects. Cross-discipline collaboration was pursued by enrolling faculty and students from diverse departments. Department chair permission was required for participation. The purpose of this qualitative study was to explore learner perspectives of the Surgical Educators Program. METHODS: Fourteen physicians completed the Surgical Educators Program. Focus groups were held with the learners who completed the 2011 and 2012 programs 6 months after completion. The groups were moderated by an educational faculty member who was not involved in any aspect of the course. Questions were designed to elicit the components of the course curriculum of significance to the learners. Narrative data were digitally recorded and transcribed verbatim, and the investigators performed independent content analyses to identify themes. The data were thematically coded and summarized using calculation of frequencies. RESULTS: Thirteen learners participated in the focus groups. Three main themes were identified. First, the program increased the participants' knowledge and practice of medical education. Second, the structure of the program was a key contributor to the outcomes. Third, the program produced a community of practice. CONCLUSIONS: This study suggests that a faculty development program comprising a diverse group of physicians consisting of readings, guided small group sessions, and a mandatory project can train plastic surgical faculty to become better surgical educators within the constraints of a busy clinical practice. PMID- 26809040 TI - The Current Role of Three-Dimensional (3D) Printing in Plastic Surgery. AB - Since the advent of three-dimensional (3D) printing in the 1980s, it is now possible to produce physical objects from digital files and create 3D objects by adding one layer at a time following a predetermined pattern. Due to the continued development of inexpensive and easy- to- use 3D printers and bioprinting, this technique has gained more momentum over time, especially in the field of medicine. This paper reviews the current and possible future application of 3D printing technology within the field of plastic and reconstructive surgery. PMID- 26809041 TI - Pedicled Perforator-Based Breast Reconstruction to Correct Breast Conservation Therapy Deformities of the Persistent Adverse Effects of Radiation Therapy. PMID- 26809043 TI - Socializing a Plastic Surgeon. PMID- 26809042 TI - Forgotten Evidence in Regenerative Cell-Based Therapy. PMID- 26809044 TI - The Case against Biofilm as the Primary Initiator of Breast Implant-Associated Anaplastic Large Cell Lymphoma. PMID- 26809045 TI - Strategies for complete mitochondrial genome sequencing on Ion Torrent PGMTM platform in forensic sciences. AB - Next generation sequencing (NGS) is a time saving and cost-efficient method to detect the complete mitochondrial genome (mtGenome) compared to Sanger sequencing. In this study we focused on developing strategies for mtGenome sequencing on the Ion Torrent PGMTM platform and NGS data analysis. With our experience, 4, 15 and 30 samples could be loaded onto Ion 314TM, Ion 316TM and Ion 318TM chips respectively at a pooling concentration of 26pM, achieving to sufficient average coverage of >=1500 * and well strand balance of 1.05. Data processing software is essential to NGS mega data analysis. The in-house Perl scripts were developed for primary data analysis to screen out uncertain positions and samples from variant call format (VCF) reports and for pedigree study to perform pairwise comparisons. The Integrative Genomic Viewer (IGV) and the NextGENe software were introduced to secondary data analysis. The mthap and EMMA were employed for haplogroup assignment. The dataset was reviewed and approved by the EMPOP as the final version, which showed 2.66% error rate generated from the Torrent Variant Caller (TVC). Across the mtGenome, 4022 variants were found at 725 nucleotide positions, where ratio of transitions to transversions was estimated at 20.89:1 and 22.18% of variants was concentrated at hypervariable segments I and II (HVS-I and HVS-II). Totally, 107 complete mtGenome haplotypes were observed from 107 Northern Chinese Han and assigned to 88 haplogroups. The random match probability (RMP) of complete mtGenome was calculated as 0.009345794, decreasing 26.19% by comparison to that of HVS-I only, and the haplotype diversity (HD) was evaluated as 1, increasing 0.33% by comparison to that of HVS-I only. Principal component analysis (PCA) showed that our population was clustered to East and Southeast Asians. The strategies in this study are suitable for complete mtGenome sequencing on Ion Torrent PGMTM platform and Northern Chinese Han (EMP00670) is the first complete mtGenome dataset contributed to the EMPOP from East Asian. PMID- 26809046 TI - Forensic and population genetic analysis of Xinjiang Uyghur population on 21 short tandem repeat loci of 6-dye GlobalFilerTM PCR Amplification kit. AB - Estimating the allele frequencies and forensic statistical parameters of commonly used short tandem repeat (STR) loci of the Uyghur population, which is the fifth largest group in China, provides a more precise reference database for forensic investigation. The 6-dye GlobalFilerTM Express PCR Amplification kit incorporates 21 autosomal STRs, which have been proven that could provide reliable DNA typing results and enhance the power of discrimination. Here we analyzed the GlobalFiler STR loci on 1962 unrelated individuals from Chinese Uyghur population of Xinjiang, China. No significant deviations from Hardy-Weinberg equilibrium and linkage disequilibrium were detected within and between the GlobalFiler STR loci. SE33 showed the greatest power of discrimination in Uyghur population, whereas TPOX showed the lowest. The combined power of discrimination was 99.999999999999999999999998746%. No significant difference was observed between Uyghur and the other two Uyghur populations at all tested STRs, as well as Dai and Mongolian. Significant differences were only observed between Uyghur and other Chinese populations at TH01, as well as Central-South Asian at D13S317, East Asian at TH01 and VWA. The phylogenetic analysis showed that Uyghur is genetically close to Chinese populations, as well as East Asian and Central-South Asian. PMID- 26809047 TI - Chromatographic NMR Spectroscopy with Hollow Silica Spheres. AB - The use of micrometric hollow silica spheres is described as a strategy to reduce magnetic field inhomogeneities in the context of NMR chromatography. When employed as a stationary phase, hollow silica microspheres allow the use of common solution-state NMR instruments to measure the diffusion coefficient perturbation induced by the interaction of the analytes with the silica surface. PMID- 26809049 TI - Establishment of a method for measuring total complement activity based on a hemolysis system using own red blood cells. AB - OBJECTIVE: To establish a simple, stable method for measuring total complement activity in plasma. METHODS: Total complement activity (TCA) of plasma was measured using a classical method (CH50 method) and a self-hemolysis colorimetric method (new method). Human red blood cells (RBCs) were used as a hemolysis indicator system and rabbit-anti-human RBC antibody instead of the traditional hemolysin (rabbit-anti-sheep RBC antibody) in the new method. TCA in intensive care unit (ICU) patients and healthy individuals was measured using the new method. RESULTS: TCA using the new method and the CH50 method were significantly correlated. TCA in ICU patients was significantly lower than that in healthy individuals. CONCLUSION: The self-hemolysis colorimetric method is a simple and stable method, and has potential value in clinical applications. PMID- 26809048 TI - A multiplex assay combining insulin, GAD, IA-2 and transglutaminase autoantibodies to facilitate screening for pre-type 1 diabetes and celiac disease. AB - At the current time, multiple candidate interventions are being proposed to abrogate or slow progression to type 1 diabetes (T1D) among islet autoantibody (iAb) positive subjects, but mass screening for eligible subjects and the general population remains a laborious and inefficient process. We have recently developed and extensively validated nonradioactive iAb assays using electrochemiluminescense (ECL) detection with an excellent sensitivity and specificity compared to the gold-standard radioassays. Using ECL detection on a platform from MesoScale Discovery (MSD) allows the measurement of four antibodies in a single well using a small blood volume (6 MUl). In the present study using a MSD QuickPlex 4-Spot plate, we successfully combined three iAb to insulin (IAA), GAD65 (GADA), and IA-2 (IA-2A) with tissue transglutaminase autoantibodies (TGA) in a single well of a 96 well plate. We tested 40 new onset T1D patients, all positive for at least one iAb and a half of them positive for TGA by radioassay, as well as 50 healthy controls. The multiplex assay retained 100% sensitivity and 100% specificity for all four autoantibodies in terms of positivity identified in patients versus normal controls compared to the corresponding standard radioassays and our single ECL assays. The multiplex ECL assay was able to identify more positivity than current radioassays for IAA and TGA. The development of this multiplex assay will facilitate high-throughput screening for T1D and celiac disease risk in the general population. PMID- 26809050 TI - Prevalence of Child Sexual Abuse in the Nordic Countries: A Literature Review. AB - This review examined child sexual abuse in the Nordic countries focusing on prevalence rates and victims' age and relationship to the perpetrator. The results show a prevalence of child sexual abuse (broadly defined) between 3-23% for boys and 11-36% for girls. The prevalence rates for contact abuse were 1-12% for boys and 6-30% for girls, while 0.3-6.8% of the boys and 1.1-13.5% of the girls reported penetrating abuse. The findings suggest an increased risk of abuse from early adolescence. In adolescence, peers may constitute the largest group of perpetrators. The results highlight the need for preventive efforts also targeting peer abuse. Future research should include cross-national and repeated studies using comparable methodology. PMID- 26809051 TI - Frequent Users of Hospital Emergency Departments in Korea Characterized by Claims Data from the National Health Insurance: A Cross Sectional Study. AB - The Korean National Health Insurance, which provides universal coverage for the entire Korean population, is now facing financial instability. Frequent emergency department (ED) users may represent a medically vulnerable population who could benefit from interventions that both improve care and lower costs. To understand the nature of frequent ED users in Korea, we analyzed claims data from a population-based national representative sample. We performed both bivariate and multivariable analyses to investigate the association between patient characteristics and frequent ED use (4+ ED visits in a year) using claims data of a 1% random sample of the Korean population, collected in 2009. Among 156,246 total ED users, 4,835 (3.1%) were frequent ED users. These patients accounted for 14% of 209,326 total ED visits and 17.2% of $76,253,784 total medical expenses generated from all ED visits in the 1% data sample. Frequent ED users tended to be older, male, and of lower socio-economic status compared with occasional ED users (p < 0.001 for each). Moreover, frequent ED users had longer stays in the hospital when admitted, higher probability of undergoing an operative procedure, and increased mortality. Among 8,425 primary diagnoses, alcohol-related complaints and schizophrenia showed the strongest positive correlation with the number of ED visits. Among the frequent ED users, mortality and annual outpatient department visits were significantly lower in the alcohol-related patient subgroup compared with other frequent ED users; furthermore, the rate was even lower than that for non-frequent ED users. Our findings suggest that expanding mental health and alcohol treatment programs may be a reasonable strategy to decrease the dependence of these patients on the ED. PMID- 26809052 TI - Antimicrobial compounds from endophytic Streptomyces sp. BCC72023 isolated from rice (Oryza sativa L.). AB - An endophytic actinomycete strain BCC72023 was isolated from rice (Oryza sativa L.) and identified as the genus Streptomyces, based on phenotypic, chemotaxonomic and 16S rRNA gene sequence analyses. The strain showed 99.80% similarity compared with Streptomyces samsunensis M1463(T). Chemical investigation led to the isolation of three macrolides, efomycins M (1), G (2) and oxohygrolidin (3), along with two polyethers, abierixin (4) and 29-O-methylabierixin (5). To our knowledge, this is the first report of efomycin M being isolated from a natural source. The compounds were identified using spectroscopic techniques and comparison with previously published data. All compounds exhibited antimalarial activity against the Plasmodium falciparum, K-1 strain, a multidrug-resistant strain, with IC50 values in a range of 1.40-5.23 MUg/ml. In addition, these compounds were evaluated for biological activity against Mycobacterium tuberculosis, Bacillus cereus, Colletotrichum gloeosporioides and Colletotrichum capsici, as well as cytotoxicity against both cancerous (MCF-7, KB, NCI-H187) and non-cancerous (Vero) cells. PMID- 26809053 TI - Discovery of a Novel er1 Allele Conferring Powdery Mildew Resistance in Chinese Pea (Pisum sativum L.) Landraces. AB - Pea powdery mildew, caused by Erysiphe pisi D.C., is an important disease worldwide. Deployment of resistant varieties is the main way to control this disease. This study aimed to screen Chinese pea (Pisum sativum L.) landraces resistant to E. pisi, and to characterize the resistance gene(s) at the er1 locus in the resistant landraces, and to develop functional marker(s) specific to the novel er1 allele. The 322 landraces showed different resistance levels. Among them, 12 (3.73%), 4 (1.24%) and 17 (5.28%) landraces showed immunity, high resistance and resistance to E. pisi, respectively. The other landraces appeared susceptible or highly susceptible to E. pisi. Most of the immune and highly resistant landraces were collected from Yunnan province. To characterize the resistance gene at the er1 locus, cDNA sequences of PsMLO1 gene were determined in 12 immune and four highly resistant accessions. The cDNAs of PsMLO1 from the immune landrace G0005576 produced three distinct transcripts, characterized by a 129-bp deletion, and 155-bp and 220-bp insertions, which were consistent with those of er1-2 allele. The PsMLO1 cDNAs in the other 15 resistant landraces produced identical transcripts, which had a new point mutation (T->C) at position 1121 of PsMLO1, indicating a novel er1 allele, designated as er1-6. This mutation caused a leucine to proline change in the amino acid sequence. Subsequently, the resistance allele er1-6 in landrace G0001778 was confirmed by resistance inheritance analysis and genetic mapping on the region of the er1 locus using populations derived from G0001778 * Bawan 6. Finally, a functional marker specific to er1-6, SNP1121, was developed using the high-resolution melting technique, which could be used in pea breeding via marker-assisted selection. The results described here provide valuable genetic information for Chinese pea landraces and a powerful tool for pea breeders. PMID- 26809054 TI - Expression and Localization of CaBP Ca2+ Binding Proteins in the Mouse Cochlea. AB - CaBPs are a family of EF-hand Ca2+ binding proteins that are structurally similar to calmodulin. CaBPs can interact with, and yet differentially modulate, effectors that are regulated by calmodulin, such as Cav1 voltage-gated Ca2+ channels. Immunolabeling studies suggest that multiple CaBP family members (CaBP1, 2, 4, and 5) are expressed in the cochlea. To gain insights into the respective auditory functions of these CaBPs, we characterized the expression and cellular localization of CaBPs in the mouse cochlea. By quantitative reverse transcription PCR, we show that CaBP1 and CaBP2 are the major CaBPs expressed in mouse cochlea both before and after hearing onset. Of the three alternatively spliced variants of CaBP1 (caldendrin, CaBP1-L, and CaBP1-S) and CaBP2 (CaBP2 alt, CaBP2-L, CaBP2-S), caldendrin and CaBP2-alt are the most abundant. By in situ hybridization, probes recognizing caldendrin strongly label the spiral ganglion, while probes designed to recognize all three isoforms of CaBP1 weakly label both the inner and outer hair cells as well as the spiral ganglion. Within the spiral ganglion, caldendrin/CaBP1 labeling is associated with cells resembling satellite glial cells. CaBP2-alt is strongly expressed in inner hair cells both before and after hearing onset. Probes designed to recognize all three variants of CaBP2 strongly label inner hair cells before hearing onset and outer hair cells after the onset of hearing. Thus, CaBP1 and CaBP2 may have overlapping roles in regulating Ca2+ signaling in the hair cells, and CaBP1 may have an additional function in the spiral ganglion. Our findings provide a framework for understanding the role of CaBP family members in the auditory periphery. PMID- 26809055 TI - A transparent bending-insensitive pressure sensor. AB - Measuring small normal pressures is essential to accurately evaluate external stimuli in curvilinear and dynamic surfaces such as natural tissues. Usually, sensitive and spatially accurate pressure sensors are achieved through conformal contact with the surface; however, this also makes them sensitive to mechanical deformation (bending). Indeed, when a soft object is pressed by another soft object, the normal pressure cannot be measured independently from the mechanical stress. Here, we show a pressure sensor that measures only the normal pressure, even under extreme bending conditions. To reduce the bending sensitivity, we use composite nanofibres of carbon nanotubes and graphene. Our simulations show that these fibres change their relative alignment to accommodate bending deformation, thus reducing the strain in individual fibres. Pressure sensitivity is maintained down to a bending radius of 80 MUm. To test the suitability of our sensor for soft robotics and medical applications, we fabricated an integrated sensor matrix that is only 2 MUm thick. We show real-time (response time of ~20 ms), large area, normal pressure monitoring under different, complex bending conditions. PMID- 26809056 TI - Electrical control of the valley Hall effect in bilayer MoS2 transistors. AB - The valley degree of freedom of electrons in solids has been proposed as a new type of information carrier, beyond the electron charge and spin. The potential of two-dimensional semiconductor transition metal dichalcogenides in valley-based electronic and optoelectronic applications has recently been illustrated through experimental demonstrations of the optical orientation of the valley polarization and of the valley Hall effect in monolayer MoS2. However, the valley Hall conductivity in monolayer MoS2, a non-centrosymmetric crystal, cannot be easily tuned, which presents a challenge for the development of valley-based applications. Here, we show that the valley Hall effect in bilayer MoS2 transistors can be controlled with a gate voltage. The gate applies an electric field perpendicular to the plane of the material, breaking the inversion symmetry present in bilayer MoS2. The valley polarization induced by the longitudinal electrical current was imaged with Kerr rotation microscopy. The polarization was found to be present only near the edges of the device channel with opposite sign for the two edges, and was out-of-plane and strongly dependent on the gate voltage. Our observations are consistent with symmetry-dependent Berry curvature and valley Hall conductivity in bilayer MoS2. PMID- 26809057 TI - Room-temperature chiral magnetic skyrmions in ultrathin magnetic nanostructures. AB - Magnetic skyrmions are chiral spin structures with a whirling configuration. Their topological properties, nanometre size and the fact that they can be moved by small current densities have opened a new paradigm for the manipulation of magnetization at the nanoscale. Chiral skyrmion structures have so far been experimentally demonstrated only in bulk materials and in epitaxial ultrathin films, and under an external magnetic field or at low temperature. Here, we report on the observation of stable skyrmions in sputtered ultrathin Pt/Co/MgO nanostructures at room temperature and zero external magnetic field. We use high lateral resolution X-ray magnetic circular dichroism microscopy to image their chiral Neel internal structure, which we explain as due to the large strength of the Dzyaloshinskii-Moriya interaction as revealed by spin wave spectroscopy measurements. Our results are substantiated by micromagnetic simulations and numerical models, which allow the identification of the physical mechanisms governing the size and stability of the skyrmions. PMID- 26809058 TI - Amyloid-carbon hybrid membranes for universal water purification. AB - Industrial development, energy production and mining have led to dramatically increased levels of environmental pollutants such as heavy metal ions, metal cyanides and nuclear waste. Current technologies for purifying contaminated waters are typically expensive and ion specific, and there is therefore a significant need for new approaches. Here, we report inexpensive hybrid membranes made from protein amyloid fibrils and activated porous carbon that can be used to remove heavy metal ions and radioactive waste from water. During filtration, the concentration of heavy metal ions drops by three to five orders of magnitude per passage and the process can be repeated numerous times. Notably, their efficiency remains unaltered when filtering several ions simultaneously. The performance of the membrane is enabled by the ability of the amyloids to selectively absorb heavy metal pollutants from solutions. We also show that our membranes can be used to recycle valuable heavy metal contaminants by thermally reducing ions trapped in saturated membranes, leading to the creation of elemental metal nanoparticles and films. PMID- 26809059 TI - Replication-Competent Influenza A and B Viruses Expressing a Fluorescent Dynamic Timer Protein for In Vitro and In Vivo Studies. AB - Influenza A and B viruses (IAV and IBV, respectively) cause annual seasonal human respiratory disease epidemics. In addition, IAVs have been implicated in occasional pandemics with inordinate health and economic consequences. Studying influenza viruses in vitro or in vivo requires the use of laborious secondary methodologies to identify infected cells. To circumvent this requirement, replication-competent infectious influenza viruses expressing an easily traceable fluorescent reporter protein can be used. Timer is a fluorescent protein that undergoes a time-dependent color emission conversion from green to red. The rate of spectral change is independent of Timer protein concentration and can be used to chronologically measure the duration of its expression. Here, we describe the generation of replication-competent IAV and IBV where the viral non-structural protein 1 (NS1) was fused to the fluorescent dynamic Timer protein. Timer expressing IAV and IBV displayed similar plaque phenotypes and growth kinetics to wild-type viruses in tissue culture. Within infected cells, Timer's spectral shift can be used to measure the rate and cell-to-cell spread of infection using fluorescent microscopy, plate readers, or flow cytometry. The progression of Timer-expressing IAV infection was also evaluated in a mouse model, demonstrating the feasibility to characterize IAV cell-to-cell infections in vivo. By providing the ability to chronologically track viral spread, Timer-expressing influenza viruses are an excellent option to evaluate the in vitro and in vivo dynamics of viral infection. PMID- 26809060 TI - The Multifaceted Aspects of Suicide Behavior. PMID- 26809061 TI - Nickel(II)-induced nasal epithelial toxicity and oxidative mitochondrial damage. AB - In probing the underlying mechanisms of nickel(II)-induced cytotoxicity on nasal epithelium, we investigated the effects of nickel(II) acetate on nasal epithelial RPMI-2650 cells. Nickel(II) elicited apoptosis, as signified by pyknotic and fragmented nuclei, increased caspase-3/7 activity, and an increase in annexin V binding, hypodiploid DNA, and Bax/Bcl-2 protein ratio. Nickel(II)-induced G2/M arrest was associated with up-regulation of p21(WAF1/CIP1) expression, decrease in phosphorylation at Thr(161) of Cdc2, and down-regulation of cyclin B1. Associated with these responses, ROS generation and mitochondrial depolarization increased in a nickel(II) concentration-dependent fashion. Pretreatment with N acetylcysteine (NAC) attenuated these changes. p53 reporter gene assay and analyses of p53, Puma, Bax, and Bcl-2 protein levels indicated that NAC inhibited nickel(II)-induced activation of p53-mediated mitochondrial apoptotic pathway. Collectively, our study provides evidences that nickel(II) may induce oxidative damage on nasal epithelium in which antioxidant NAC protects cells against nickel(II)-induced apoptosis through the prevention of oxidative stress-mediated mitochondrial damage. PMID- 26809062 TI - Lipid emulsion reverses bupivacaine-induced apoptosis of h9c2 cardiomyocytes: PI3K/Akt/GSK-3beta signaling pathway. AB - Some findings have suggested that the rescue of bupivacaine (BPV)-induced cardiotoxicity by lipid emulsion (LE) is associated with inhibition of mitochondrial permeability transition pore (mPTP). However, the mechanism of this rescue action is not clearly known. In this study, the roles of phosphoinositide 3-kinase (PI3K)/Akt and glycogen synthase kinase-3beta (GSK-3beta) in the molecular mechanism of LE-induced protection and its relationship with mPTP were explored. h9c2 cardiomyocytes were randomly divided into several groups: control, BPV, LE, BPV+LE. To study the effect of LE on mPTP, atractyloside (Atr, 20 MUM, mPTP opener) and cyclosporine A (CsA, 10 MUM, mPTP blocker) were used. To unravel whether LE protects heart through the PI3K/Akt/GSK-3beta signaling pathway, cells were treated with LY294002 (LY, 30 MUM, PI3K blocker) or TWS119 (TWS 10 MUM, GSK 3beta blocker). Later mitochondrial respiratory chain complexes, apoptosis, opening of mPTP and phosphorylation levels of Akt/GSK-3beta were measured. LE significantly improved the mitochondrial functions in h9c2 cardiomyocytes. LE reversed the BPV-induced apoptosis and the opening of mPTP. The effect of LE was not only enhanced by CsA and TWS, but also abolished by Atr and LY. LE also increased the phosphorylation levels of Akt and GSK-3beta. These results suggested that LE can reverse the apoptosis in cardiomyocytes by BPV and a mechanism of its action is inhibition of mPTP opening through the PI3K/Akt/GSK 3beta signaling pathway. PMID- 26809063 TI - Epidemiology and Clinical Burden of Malaria in the War-Torn Area, Orakzai Agency in Pakistan. AB - BACKGROUND: Military conflict has been a major challenge in the detection and control of emerging infectious diseases such as malaria. It poses issues associated with enhancing emergence and transmission of infectious diseases by destroying infrastructure and collapsing healthcare systems. The Orakzai agency in Pakistan has witnessed a series of intense violence and destruction. Military conflicts and instability in Afghanistan have resulted in the migration of refugees into the area and possible introduction of many infectious disease epidemics. Due to the ongoing violence and Talibanization, it has been a challenge to conduct an epidemiological study. METHODOLOGY/PRINCIPAL FINDINGS: All patients were sampled within the transmission season. After a detailed clinical investigation of patients, data were recorded. Baseline venous blood samples were taken for microscopy and nested polymerase chain reaction (nPCR) analysis. Plasmodium species were detected using nested PCR (nPCR) and amplification of the small subunit ribosomal ribonucleic acid (ssrRNA) genes using the primer pairs. We report a clinical assessment of the epidemic situation of malaria caused by Plasmodium vivax (86.5%) and Plasmodium falciparum (11.79%) infections with analysis of complications in patients such as decompensated shock (41%), anemia (8.98%), hypoglycaemia (7.3%), multiple convulsions (6.7%), hyperpyrexia (6.17%), jaundice (5%), and hyperparasitaemia (4.49%). CONCLUSIONS/SIGNIFICANCE: This overlooked distribution of P. vivax should be considered by malaria control strategy makers in the world and by the Government of Pakistan. In our study, children were the most susceptible population to malaria infection while they were the least expected to use satisfactory prevention strategies in such a war-torn deprived region. Local health authorities should initiate malaria awareness programs in schools and malaria related education should be further promoted at the local level reaching out to both children and parents. PMID- 26809064 TI - Cell Wall N-Linked Mannoprotein Biosynthesis Requires Goa1p, a Putative Regulator of Mitochondrial Complex I in Candida albicans. AB - The Goa1p of Candida albicans regulates mitochondrial Complex I (CI) activities in its role as a putative CI accessory protein. Transcriptional profiling of goa1? revealed a down regulation of genes encoding beta-oligomannosyl transferases. Herein, we present data on cell wall phenotypes of goa1? (strain GOA31). We used transmission electron microscopy (TEM), GPC/MALLS, and NMR to compare GOA31 to a gene-reconstituted strain (GOA32) and parental cells. We note by TEM a reduction in outer wall fibrils, increased inner wall transparency, and the loss of a defined wall layer close to the plasma membrane. GPC-MALLS revealed a reduction in high and intermediate Mw mannan by 85% in GOA31. A reduction of beta-mannosyl but not alpha-mannosyl linkages was noted in GOA31 cells. beta (1,6)-linked glucan side chains were branched about twice as often but were shorter in length for GOA31. We conclude that mitochondrial CI energy production is highly integrated with cell wall formation. Our data also suggest that not all cell wall biosynthetic processes are dependent upon Goa1p even though it provides high levels of ATP to cells. The availability of both broadly conserved and fungal-specific mutants lacking CI subunit proteins should be useful in assessing functions of fungal-specific functions subunit proteins. PMID- 26809065 TI - Cardio-Metabolic Disease Risks and Their Associations with Circulating 25 Hydroxyvitamin D and Omega-3 Levels in South Asian and White Canadians. AB - OBJECTIVES: This study compared cardio-metabolic disease risk factors and their associations with serum vitamin D and omega-3 status in South Asian (SAC) and White Canadians (WC) living in Canada's capital region. METHODS: Fasting blood samples were taken from 235 SAC and 279 WC aged 20 to 79 years in Ottawa, and 22 risk factors were measured. RESULTS: SAC men and women had significantly higher fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), apolipoprotein B (ApoB), ratios of total (TC) to HDL cholesterol (HDLC) and ApoB to ApoA1, leptin, E-selectin, P-selectin, ICAM-1 and omega-3 (p < 0.05), but lower HDLC, ApoA1, vitamin D levels than WC (p < 0.05). SAC women had higher CRP and VEGF than WC women. Adequate (50-74.9 nmol/L) or optimal (>= 75 nmol/L) levels of 25(OH)D were associated with lower BMI, glucose, insulin, HOMA IR, TG, TC, low density lipoprotein cholesterol (LDLC), ApoB/ApoA1 ratio, CRP, leptin, and higher HDLC, ApoA1, omega-3 index, L-selectin levels in WC, but not in SAC. Intermediate (>4%-<8%) or high (>= 8%) levels of omega-3 indices were related to lower E-selectin, P-selectin, ICAM-1 and higher HDLC, 25(OH)D levels in WC, but not in SAC. The BMIs of <= 25 kg/m2 were related to lower LDLC, ApoB, VEGF, creatinine and higher 25(OH)D in WC, but not in SAC. CONCLUSIONS: The associations of vitamin D, omega-3 status, BMI and risk factors were more profound in the WC than SAC. Compared to WC, vitamin D status and omega-3 index may not be good predictive risk factors for the prevalence of CVD and diabetes in SAC. PMID- 26809066 TI - A Novel Method for Quantifying the Inhaled Dose of Air Pollutants Based on Heart Rate, Breathing Rate and Forced Vital Capacity. AB - To better understand the interaction of physical activity and air pollution exposure, it is important to quantify the change in ventilation rate incurred by activity. In this paper, we describe a method for estimating ventilation using easily-measured variables such as heart rate (HR), breathing rate (fB), and forced vital capacity (FVC). We recruited healthy adolescents to use a treadmill while we continuously measured HR, fB, and the tidal volume (VT) of each breath. Participants began at rest then walked and ran at increasing speed until HR was 160-180 beats per minute followed by a cool down period. The novel feature of this method is that minute ventilation ([Formula: see text]) was normalized by FVC. We used general linear mixed models with a random effect for subject and identified nine potential predictor variables that influence either [Formula: see text] or FVC. We assessed predictive performance with a five-fold cross validation procedure. We used a brute force selection process to identify the best performing models based on cross-validation percent error, the Akaike Information Criterion and the p-value of parameter estimates. We found a two predictor model including HR and fB to have the best predictive performance ([Formula: see text]/FVC = -4.247+0.0595HR+0.226fB, mean percent error = 8.1+/ 29%); however, given the ubiquity of HR measurements, a one-predictor model including HR may also be useful ([Formula: see text]/FVC = -3.859+0.101HR, mean percent error = 11.3+/-36%). PMID- 26809067 TI - Role of Periostin in Adhesion and Migration of Bone Remodeling Cells. AB - Periostin is an extracellular matrix protein highly expressed in collagen-rich tissues subjected to continuous mechanical stress. Functionally, periostin is involved in tissue remodeling and its altered function is associated to numerous pathological processes. In orthodontics, periostin plays key roles in the maintenance of dental tissues and it is mainly expressed in those areas where tension or pressing forces are taking place. In this regard, high expression of periostin is essential to promote migration and proliferation of periodontal ligament fibroblasts. However little is known about the participation of periostin in migration and adhesion processes of bone remodeling cells. In this work we employ the mouse pre-osteoblastic MC3T3-E1 and the macrophage-like RAW 264.7 cell lines to overexpress periostin and perform different cell-based assays to study changes in cell behavior. Our data indicate that periostin overexpression not only increases adhesion capacity of MC3T3-E1 cells to different matrix proteins but also hampers their migratory capacity. Changes on RNA expression profile of MC3T3-E1 cells upon periostin overexpression have been also analyzed, highlighting the alteration of genes implicated in processes such as cell migration, adhesion or bone metabolism but not in bone differentiation. Overall, our work provides new evidence on the impact of periostin in osteoblasts physiology. PMID- 26809068 TI - Effect of Proteinuria and Glomerular Filtration Rate on Renal Outcome in Patients with Biopsy-Proven Benign Nephrosclerosis. AB - BACKGROUND: Reduced estimated glomerular filtration rate (eGFR) and proteinuria are risk factors for end-stage renal disease (ESRD), of which benign nephrosclerosis is a common cause. However, few biopsy-based studies have assessed these associations. METHODS: We performed retrospective cohort study of 182 Japanese patients who underwent renal biopsy from June 1985 through March 2014 and who were diagnosed with benign nephrosclerosis. Competing risk regression analyses were used to investigate the effect of eGFR and proteinuria levels at the time of renal biopsy on the risk for renal events (ESRD or a 50% decline in eGFR from baseline). RESULTS: During a median 5.8-year follow-up, 63 (34.6%) patients experienced renal events. The incidence of renal events increased with lower baseline eGFR and greater baseline proteinuria levels. After adjustment for baseline covariates, lower eGFR levels (subhazard ratios [SHRs], 1.30; 95% confidence interval [CI], 1.01-1.67, per 10 mL/min/1.73 m2) and higher proteinuria levels (SHR, 1.52; 95% CI, 1.23-1.87, per 1.0 g/day) at the time of renal biopsy were associated independently with higher risk for renal events. Lower levels of serum albumin (SHR, 2.07; 95% CI, 1.20-3.55 per 1.0 g/dL) were also associated with renal events. Patients with both eGFR <30 mL/min/1.73 m2 and proteinuria >=0.5 g/day had a 26.7-fold higher risk (95% CI, 3.97-179.4) of renal events than patients with both eGFR >=60 mL/min/1.73 m2 and proteinuria <0.5 g/day. CONCLUSIONS: Reduced eGFR and increased proteinuria as well as lower serum albumin at the time of renal biopsy are independent risk factors for renal events among patients with biopsy-proven benign nephrosclerosis. PMID- 26809069 TI - Urologist Participation in Medicare Shared Savings Program Accountable Care Organizations (ACOs). AB - OBJECTIVE: To understand the current role of urologists in Medicare Shared Savings Program (MSSP) Accountable Care Organizations (ACOs) and the organizational characteristics of ACOs with participating urologists. MATERIALS AND METHODS: Using 2012-2013 Medicare data and the National Provider Identifier Database, we classified each urologist in the U.S. and Puerto Rico as either an MSSP ACO participant or nonparticipating provider. We then examined the distribution of ACO-participating urologists across the U.S. and among the first 220 MSSP ACOs. We also compared the characteristics of ACOs with and without participating urologists. RESULTS: Among 11,084 identified urologists, 1118 (10%) were MSSP ACO participants. ACO-participating urologists practiced more frequently in the Northeast and Midwest (P < .001), and were more commonly female (10% vs 8%, P = .003). At an organizational level, only 110 (50%) of the initial MSSP ACOs included at least one urologist; among this group, the number of participating urologists ranged from 1 to 55. ACOs with one or more participating urologist were larger organizations, with respect to both the number of assigned beneficiaries and the number of providers per 1000 beneficiaries (P < .001 for each comparison). The patient populations served by ACOs with and without urologists were similar (P > .05 for each comparison). CONCLUSION: A modest percentage of urologists participate in MSSP ACOs, although many of these organizations still lack any formal involvement by urological surgeons. Without such participation, improving the coordination, quality, and cost of urologic care for Medicare beneficiaries may be more challenging. PMID- 26809070 TI - Re: Kryvenko et al.: Prostate-specific Antigen Mass Density - A Measure Predicting Prostate Cancer Volume and Accounting for Overweight and Obesity related Prostate-specific Antigen Hemodilution (Urology, 2016;90:141-147). PMID- 26809071 TI - Decipher Genomic Classifier Measured on Prostate Biopsy Predicts Metastasis Risk. AB - OBJECTIVES: To evaluate the ability of the Decipher genomic classifier in predicting metastasis from analysis of prostate needle biopsy diagnostic tumor tissue specimens. MATERIALS AND METHODS: Fifty-seven patients with available biopsy specimens were identified from a cohort of 169 men treated with radical prostatectomy in a previously reported Decipher validation study at Cleveland Clinic. A Cox multivariable proportional hazards model and survival C-index were used to evaluate the performance of Decipher. RESULTS: With a median follow up of 8 years, 8 patients metastasized and 3 died of prostate cancer. The Decipher plus National Comprehensive Cancer Network (NCCN) model had an improved C-index of 0.88 (95% confidence interval [CI] 0.77-0.96) compared to NCCN alone (C-index 0.75, 95% CI 0.64-0.87). On multivariable analysis, Decipher was the only significant predictor of metastasis when adjusting for age, preoperative prostate specific antigen and biopsy Gleason score (Decipher hazard ratio per 10% increase 1.72, 95% CI 1.07-2.81, P = .02). CONCLUSION: Biopsy Decipher predicted the risk of metastasis at 10 years post radical prostatectomy. While further validation is required on larger cohorts, preoperative knowledge of Decipher risk derived from biopsy could indicate the need for multimodality therapy and help set patient expectations of therapeutic burden. PMID- 26809072 TI - An efficient scheme for sampling fast dynamics at a low average data acquisition rate. AB - We introduce a temporal scheme for data sampling, based on a variable delay between two successive data acquisitions. The scheme is designed so as to reduce the average data flow rate, while still retaining the information on the data evolution on fast time scales. The practical implementation of the scheme is discussed and demonstrated in light scattering and microscopy experiments that probe the dynamics of colloidal suspensions using CMOS or CCD cameras as detectors. PMID- 26809073 TI - Structural requirements for potential HIV-integrase inhibitors identified using pharmacophore-based virtual screening and molecular dynamics studies. AB - Acquired immunodeficiency syndrome (AIDS) is a life-threatening disease which is a collection of symptoms and infections caused by a retrovirus, human immunodeficiency virus (HIV). There is currently no curative treatment and therapy is reliant on the use of existing anti-retroviral drugs. Pharmacoinformatics approaches have already proven their pivotal role in the pharmaceutical industry for lead identification and optimization. In the current study, we analysed the binding preferences and inhibitory activity of HIV integrase inhibitors using pharmacoinformatics. A set of 30 compounds were selected as the training set of a total 540 molecules for pharmacophore model generation. The final model was validated by statistical parameters and further used for virtual screening. The best mapped model (R = 0.940, RMSD = 2.847, Q(2) = 0.912, se = 0.498, Rpred(2) = 0.847 and rm(test)(2) = 0.636) explained that two hydrogen bond acceptor and one aromatic ring features were crucial for the inhibition of HIV-integrase. From virtual screening, initial hits were sorted using a number of parameters and finally two compounds were proposed as promising HIV-integrase inhibitors. Drug-likeness properties of the final screened compounds were compared to FDA approved HIV-integrase inhibitors. HIV-integrase structure in complex with the most active and final screened compounds were subjected to 50 ns molecular dynamics (MD) simulation studies to check comparative stability of the complexes. The study suggested that the screened compounds might be promising HIV-integrase inhibitors. The new chemical entities obtained from the NCI database will be subjected to experimental studies to confirm potential inhibition of HIV integrase. PMID- 26809074 TI - Pregnant women in vehicles: Driving habits, position and risk of injury. AB - This study proposed to broadly examine vehicle use by pregnant women in order to improve realism of accident simulations involving these particular occupants. Three research pathways were developed: the first consisted in a questionnaire survey examining the driving habits of 135 pregnant women, the second obtained measurements of 15 pregnant women driving position in their own vehicle from the 6th to the 9th month of pregnancy by measuring distances between body parts and vehicle parts, and the third examined car accidents involving pregnant occupants. Results obtained indicate that between 90% and 100% of pregnant women wore their seat belts whatever their stage of pregnancy, although nearly one third of subjects considered the seat belt was dangerous for their unborn child. The measurements obtained also showed that the position of the pregnant woman in her vehicle, in relation to the various elements of the passenger compartment, changed significantly during pregnancy. In the studied accidents, no correlation was found between the conditions of the accident and the resulting fetal injury. Results reveal that pregnant women do not modify significantly the seat setting as a function of pregnancy stage. Only the distance between maternal abdomen and steering wheel change significantly, from 16 cm to 12 cm at 6 and 9 month respectively. Pregnant women are mainly drivers before 8 months of pregnancy, passengers after that. Car use frequency falls down rapidly from 6 to 9 months of pregnancy. Real crashes investigations indicate a low rate of casualties, i.e. 342 car accidents involving pregnant women for a period of 9 years in an approximately 1.7 million inhabitants area. No specific injury was found as a function of stage of pregnancy. PMID- 26809075 TI - A hybrid finite mixture model for exploring heterogeneous ordering patterns of driver injury severity. AB - Debates on the ordering patterns of crash injury severity are ongoing in the literature. Models without proper econometrical structures for accommodating the complex ordering patterns of injury severity could result in biased estimations and misinterpretations of factors. This study proposes a hybrid finite mixture (HFM) model aiming to capture heterogeneous ordering patterns of driver injury severity while enhancing modeling flexibility. It attempts to probabilistically partition samples into two groups in which one group represents an unordered/nominal data-generating process while the other represents an ordered data-generating process. Conceptually, the newly developed model offers flexible coefficient settings for mining additional information from crash data, and more importantly it allows the coexistence of multiple ordering patterns for the dependent variable. A thorough modeling performance comparison is conducted between the HFM model, and the multinomial logit (MNL), ordered logit (OL), finite mixture multinomial logit (FMMNL) and finite mixture ordered logit (FMOL) models. According to the empirical results, the HFM model presents a strong ability to extract information from the data, and more importantly to uncover heterogeneous ordering relationships between factors and driver injury severity. In addition, the estimated weight parameter associated with the MNL component in the HFM model is greater than the one associated with the OL component, which indicates a larger likelihood of the unordered pattern than the ordered pattern for driver injury severity. PMID- 26809076 TI - Correction: A Mixed-Method Approach for Quantifying Illegal Fishing and Its Impact on an Endangered Fish Species. PMID- 26809077 TI - Molecular Characterization of E-Type Prostanoid Receptor 4 (EP4) from Ayu (Plecoglossus altivelis) and Its Functional Analysis in the Monocytes/Macrophages. AB - Prostaglandin E2 (PGE2) plays an important role in a broad spectrum of physiological and pathological processes by interacting with E-type prostanoid receptors (EPs). EP4 is one of four EP subtypes known to mediate the immune response in mammalian monocytes/macrophages. However, the precise function and characteristics of EP4 in fish remain unclear. In this study, we characterized a novel EP4-like (PaEP4L) gene from ayu, Plecoglossus altivelis. The cDNA sequence of PaEP4L is 2781 nucleotides (nts) in length, encoding a polypeptide of 459 amino acid residues with a calculated molecular weight of 51.17 kDa. Sequence comparison and phylogenetic tree analysis showed that PaEP4L shared 76% amino acid identity with that of the Atlantic salmon (Salmo salar). PaEP4L mRNA was detected by real-time quantitative PCR (QPCR) in all tested tissues and head kidney-derived monocytes/macrophages (MO/MF). It varied greatly in liver, spleen and MO/MF upon Vibrio anguillarum infection. Western blot analysis revealed a significant increase of PaEP4L in cell homogenates from ayu MO/MF upon V. anguillarum infection. Moreover, anti-PaEP4L IgG reversed the down-regulation of interleukin 1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) mRNA expression as well as phagocytosis in ayu MO/MF caused by PGE2. There were no significant differences in the respiratory burst response between PGE2 treated and untreated cells. We further found that cAMP mediated PGE2/PaEP4L signal in ayu MO/MF. In conclusion, our results indicate that PaEP4L mediates PGE2 effects on ayu MO/MF function, revealing that EP4 also plays a role in the modulation of cells of the fish's innate immune system. PMID- 26809078 TI - Immunotherapy for advanced melanoma: future directions. AB - As calculated by the meta-analysis of Korn et al., the prognosis of metastatic melanoma in the pretarget and immunological therapy era was poor, with a median survival of 6.2 and a 1-year life expectancy of 25.5%. Nowadays, significant advances in melanoma treatment have been gained, and immunotherapy is one of the promising approaches to get to durable responses and survival improvement. The aim of the present review is to highlight the recent innovations in melanoma immunotherapy and to propose a critical perspective of the future directions of this enthralling oncology subspecialty. PMID- 26809079 TI - Biological effects of mechanically and chemically dispersed oil on the Icelandic scallop (Chlamys islandica). AB - This study aimed to simulate conditions in which dispersant (Dasic NS) might be used to combat an oil spill in coastal sub-Arctic water of limited depth and water exchange in order to produce input data for Net Environmental Benefit Analysis (NEBA) of Arctic and sub-Arctic coastal areas. Concentration dependent differences in acute responses and long-term effects of a 48h acute exposure to dispersed oil, with and without the application of a chemical dispersant, were assessed on the Arctic filter feeding bivalve Chlamys islandica. Icelandic scallops were exposed for 48h to a range of spiked concentrations of mechanically and chemically dispersed oil. Short-term effects were assessed in terms of lysosomal membrane stability, superoxide dismutase, catalase, gluthatione S transferases, glutathione peroxidases, glutathione reductase, glutathione, total oxyradical scavenging capacity, lipid peroxidation and peroxisomal proliferation. Post-exposure survival, growth and reproductive investment were followed for 2 months to evaluate any long-term consequence. Generally, similar effects were observed in scallops exposed to mechanically and chemically dispersed oil. Limited short-term effects were observed after 48h, suggesting that a different timing would be required for measuring the possible onset of such effects. There was a concentration dependent increase in cumulative post-exposure mortality, but long-term effects on gonadosomatic index, somatic growth/condition factor did not differ among treatments. PMID- 26809080 TI - Application of the micronucleus test and comet assay in Trachemys callirostris erythrocytes as a model for in situ genotoxic monitoring. AB - Trachemys callirostris is a turtle species endemic to northern South America. In northern Colombia it occurs in the middle and lower Magdalena River drainage and its principal tributaries (lower Cauca and San Jorge rivers) and in other minor drainages such as the lower Sinu River. In recent years, industrial, agricultural, and mining activities have altered natural habitats in Colombia where this species occurs, and many of the pollutants released there are known to induce genetic alterations in wildlife species. The micronucleus test and comet assay are two of the most widely used methods to characterize DNA damage induced by physical and chemical agents in wildlife species, but have not been employed previously for genotoxic evaluations in T. callirostris. The goal of this study was to optimize these genotoxic biomarkers for T. callirostris erythrocytes in order to establish levels of DNA damage in this species and thereby evaluate its potential as a sentinel species for monitoring genotoxic effects in freshwater environments in northern Colombia. Both genotoxic techniques were applied on peripheral blood erythrocytes from 20 captive-reared T. callirostris individuals as a negative control, as well as from samples obtained from 49 individuals collected in Magangue (Magdalena River drainage) and 24 individuals collected in Lorica (Sinu River drainage) in northern Colombia. Negative control individuals exhibited a baseline frequency of micronuclei of 0.78+/-0.58 and baseline values for comet tail length and tail moment of 3.34+/-0.24um and 10.70+/-5.5, respectively. In contrast, samples from both field sites exhibited significantly greater evidence of genotoxic effects for both tests. The mean MN frequencies in the samples from Magangue and Lorica were 8.04+/-7.08 and 12.19+/-12.94, respectively. The mean tail length for samples from Magangue and Lorica were 5.78+/-3.18 and 15.46+/-7.39, respectively. Finally, the mean tail moment for samples from Magangue and Lorica were 23.59+/-18.22 and 297.94+/-242.18, respectively. The frequency of micronuclei in the samples was positively related to comet tail length and tail moment. Thus, this study showed that both genotoxicity biomarkers may be applied to T. callirostris erythrocytes as a sentinel organism for assessing the effects of environmental pollutants in freshwater ecosystems in northern South America. PMID- 26809081 TI - First North American 50 cc Total Artificial Heart Experience: Conversion from a 70 cc Total Artificial Heart. AB - The 70 cc total artificial heart (TAH) has been utilized as bridge to transplant (BTT) for biventricular failure. However, the utilization of 70 cc TAH has been limited to large patients for the low output from the pulmonary as well as systemic vein compression after chest closure. Therefore, the 50 cc TAH was developed by SynCardia (Tucson, AZ) to accommodate smaller chest cavity. We report the first TAH exchange from a 70 to 50 cc due to a fit difficulty. The patient failed to be closed with a 70 cc TAH, although the patient met the conventional 70 cc TAH fit criteria. We successfully closed the chest with a 50 cc TAH. PMID- 26809082 TI - Cardiopulmonary Bypass with Low- Versus High-Priming Volume: Comparison of Inflammatory Responses in a Rat Model. AB - A cardiopulmonary bypass (CPB) can preserve life. However, interactions between blood and large artificial surfaces might help to provoke a series of chain reactions during CPB that result in the formation and release of numerous powerful inflammatory mediators including hormones and autacoids. We postulated that small CPB circuits with reduced priming volumes and less surface areas that come into contact with blood would attenuate systemic inflammatory responses by reducing the levels of cytokines and organ tissue damage during CPB. Rats were assigned to groups that underwent CPB with a high priming volume (PV) of 15 ml and a surface area of 0.044 m or a low PV of 7 ml and a surface area of 0.034 m. We measured serum levels of cytokines and biochemical markers during CPB. Levels of proinflammatory cytokines and biochemical markers were significantly elevated in the group with a high PV, than low PV at 60 min, whereas none of these factors significantly differed between the groups at 120 min. These data suggested that in addition to blood being in contact with surfaces, the duration of CPB exposure is also an important factor for nonlinear time variances in damage caused by the systemic inflammatory response. PMID- 26809083 TI - Driveline Infection Risk with Utilization of a Temporary External Anchoring Suture After Implantation of a Left Ventricular Assist Device. AB - Driveline infections (DLI) are a cause of morbidity after continuous-flow left ventricular assist device (CF-LVAD) implantation. Because driveline trauma contributes to DLI, we assessed whether intraoperative placement of a temporary external anchoring suture (EAS) influenced DLI rate. We analyzed 161 consecutive patients with CF-LVAD (HMII 82; HW 79) implantation. Two groups were defined: placement of EAS (n = 85) or No EAS (n = 76). For NO EAS patients, the driveline was permanently anchored internally to the rectus fascia. Cox proportional analysis was performed to assess the effect of EAS on time to first confirmed DLI. Baseline characteristics were comparable between groups (all p = 0.3). Mean follow-up time was 0.93 years. A total of 18 (11.1%) patients developed confirmed culture positive DLI, with "first infection" rate of 0.13 events/year. Mean time to confirmed DLI was 0.69 years. Driveline infection was less likely (hazard ratio [HR] = 0.28, 0.95 confidence interval [CI] = 0.06-1.25, p = 0.056) to occur in NO EAS (2/18) then in EAS (16/18). Confirmed DLI was comparable between device types (p = 0.3). Multivariable regression adjusted for age, BMI, blood product use, device type, and diabetes showed equivocal effect of EAS (HR = 0.33, 0.95 CI = 0.07-1.54, p = 0.12). Patients with a temporary EAS may have an increased risk of confirmed DLI after device implantation. PMID- 26809084 TI - Development of a Mock Extracorporeal Membrane Oxygenation Circuit to Assess Recirculation. AB - A limitation of veno-venous extracorporeal membrane oxygenation (VV-ECMO) is the recirculating of newly oxygenated blood back to the VV-ECMO circuit. We compared cannulation strategies for combating recirculation utilizing a mock circulation loop (MCL) with ultrasonic flow probes and pressure transducers ensuring that the MCL was run at physiological hemodynamic parameters. Mean recirculation percentages were lower (ANOVA, F = 14.25; p = 0.0001) with the Wang-Zwische dual lumen cannula (4.00 +/- 1.77, n = 7) than both the femoro-jugular (15.23 +/- 7.00, n = 8) and the femoro-femoral cannulation configurations (13.49 +/- 1.44, n = 8). PMID- 26809085 TI - Point-of-Care Rapid-Seeding Ventricular Assist Device with Blood-Derived Endothelial Cells to Create a Living Antithrombotic Coating. AB - The most promising alternatives to heart transplantation are left ventricular assist devices and artificial hearts; however, their use has been limited by thrombotic complications. To reduce these, sintered titanium (Ti) surfaces were developed, but thrombosis still occurs in approximately 7.5% of patients. We have invented a rapid-seeding technology to minimize the risk of thrombosis by rapid endothelialization of sintered Ti with human cord blood-derived endothelial cells (hCB-ECs). Human cord blood-derived endothelial cells were seeded within minutes onto sintered Ti and exposed to thrombosis-prone low fluid flow shear stresses. The hCB-ECs adhered and formed a confluent endothelial monolayer on sintered Ti. The exposure of sintered Ti to 4.4 dynes/cm for 20 hr immediately after rapid seeding resulted in approximately 70% cell adherence. The cell adherence was not significantly increased by additional ex vivo static culture of rapid-seeded sintered Ti before flow exposure. In addition, adherent hCB-ECs remained functional on sintered Ti, as indicated by flow-induced increase in nitric oxide secretion and reduction in platelet adhesion. After 15 day ex vivo static culture, the adherent hCB-ECs remained metabolically active, expressed endothelial cell functional marker thrombomodulin, and reduced platelet adhesion. In conclusion, our results demonstrate the feasibility of rapid-seeding sintered Ti with blood-derived hCB-ECs to generate a living antithrombotic surface. PMID- 26809086 TI - Darcy Permeability of Hollow Fiber Membrane Bundles Made from Membrana Polymethylpentene Fibers Used in Respiratory Assist Devices. AB - Hollow fiber membranes (HFMs) are used in blood oxygenators for cardiopulmonary bypass or in next generation artificial lungs. Flow analyses of these devices is typically done using computational fluid dynamics (CFD) modeling HFM bundles as porous media, using a Darcy permeability coefficient estimated from the Blake Kozeny (BK) equation to account for viscous drag from fibers. We recently published how well this approach can predict Darcy permeability for fiber bundles made from polypropylene HFMs, showing the prediction can be significantly improved using an experimentally derived correlation between the BK constant (A) and bundle porosity (epsilon). In this study, we assessed how well our correlation for A worked for predicting the Darcy permeability of fiber bundles made from Membrana polymethylpentene (PMP) HFMs, which are increasingly being used clinically. Swatches in the porosity range of 0.4 to 0.8 were assessed in which sheets of fiber were stacked in parallel, perpendicular, and angled configurations. Our previously published correlation predicted Darcy within +/ 8%. A new correlation based on current and past measured permeability was determined: A = 497epsilon - 103; using this correlation measured Darcy permeability was within +/-6%. This correlation varied from 8% to -3.5% of our prior correlation over the tested porosity range. PMID- 26809087 TI - Blood Product Utilization with Left Ventricular Assist Device Implantation: A Decade of Statewide Data. AB - Blood transfusion rates with cardiac surgery over time have decreased, this trend has not been examined for patients undergoing left ventricular assist device (LVAD) implantation. We investigated blood transfusion trends with LVAD implantation in a statewide database. Between July 2004 and June 2014, 666 LVADs were implanted (age 54.5 +/- 12.6 years. 77% men). Reoperation for bleeding was required in 22% of cases. Postoperative mortality was 13.2%. Over the decade, use of any blood products with LVAD surgery by year ranged from 83% to 100% (92 +/- 5.3%). Intraoperative and postoperative blood products use was 71.8% and 73%, respectively. Only 7.4% of patients did not receive any blood products. Blood transfusion during surgery consisted of plasma (60%), platelets (56%), red blood cells (RBCs) (44.3%), and cryoprecipitate (32%), whereas after surgery RBC use was more frequent (68%). Compared with the initial 5 years (2005-2009), the units of blood transfused in the second 5 years (2010-2014) were significantly less, 21 +/- 23 units vs. 16.6 +/- 20.5 units, p = 0.0038. By multivariable analysis, preoperative factors predictive of blood transfusion are lower hematocrit, lower BMI, reoperative surgery, requirement for intraaortic balloon pump (IABP), and nonelective surgery. Blood transfusion with LVAD implantation remains very high. However, the amount of blood product transfused has decreased in the last 5 years. PMID- 26809088 TI - Arrhythmias in Patients with Cardiac Implantable Electrical Devices after Implantation of a Left Ventricular Assist Device. AB - Utilization of continuous-flow left ventricular assist devices (CF-LVADs) for advanced heart failure is increasing, and the role of cardiac implantable electrical devices (CIED) is unclear. Prior studies of the incidence of arrhythmias and shocks are frequently limited by ascertainment. One hundred and seventy-eight patients were examined with a previous CIED who were implanted with a CF-LVAD. Medical history, medications, and CIED data from device interrogations were gathered. A cardiac surgery control group (n = 38) was obtained to control for surgical factors. Several clinically significant events increased after LVAD implantation: treated-zone ventricular arrhythmias (VA; p < 0.01), monitored-zone VA (p < 0.01), antitachycardia pacing (ATP)-terminated episodes (p < 0.01), and shocks (p = 0.01), although administered shocks later decreased (p < 0.01). Presence of a preimplant VA was associated with postoperative VA (odds ratio [OR]: 4.31; confidence interval [CI]: 1.5-12.3, p < 0.01). Relative to cardiac surgery, LVAD patients experienced more perioperative events (i.e., monitored VAs and shocks, p < 0.01 and p = 0.04). Neither implantable cardioverter defibrillator (ICD) shocks before implant nor early or late postimplant arrhythmias or shocks predicted survival (p = 0.07, p = 0.55, and p = 0.55). Our experience demonstrates time-dependent effects on clinically significant arrhythmias after LVAD implantation, including evidence that early LVAD-related arrhythmias may be caused by the unique arrhythmogenic effects of VAD implant. PMID- 26809089 TI - BRI1-EMS-suppressor 1 gain-of-function mutant shows higher susceptibility to necrotrophic fungal infection. AB - Brassinosteroids (BRs) are plant-specific steroids that are involved in plant growth and defense responses. However, the exact roles of BR in plant defense are unclear. We used the bes1-D gain-of-function mutant to define the underlying relationship between plant growth and defense through BR signaling and innate immunity. In bes1-D, further downstream component BES1 transcription factor is stabilized, leading to the activation of BR signaling. Previous reports on BES1 target genes showed that approximately 10% are related to biotic stress responses. Therefore, the bes1-D PTI responses were examined. The bes1-D mutant was specifically susceptible to Alternaria brassicicola, a necrotrophic fungus, which successfully produced spore, resulting in considerable cell death. However, it was not affected by a biotrophic pathogen, Pseudomonas syringae pv. tomato (Pst) DC3000. Instead of a ROS burst, a representative initial PTI responses, higher ROS accumulation was sustained in bes1-D than in the wild type plant. PDF1.2 expression was not induced in response to fungal pathogen infection in bes1-D. These results suggest that BES1 is also involved in JA-related defense responses, especially in response to necrotrophic pathogens. PMID- 26809090 TI - Inhibition of miR-222-3p activity promoted osteogenic differentiation of hBMSCs by regulating Smad5-RUNX2 signal axis. AB - miRNAs are recently found playing important roles in osteogenesis. In this study, we identified that miR-222-3p decreased during osteogenic differentiation of human mesenchymal stem cells (hBMSCs) using Quantitative Real-Time Reverse Transcription PCR (qRT-PCR). Furthermore, we investigated the effect of miR-222 3p on osteogenic differentiation of hBMSCs. Inhibition of miR-222-3p function in hBMSCs using infection of lentiviruses carrying miR-222-3p specific inhibitor promoted expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Whereas, overexpression of miR-222-3p inhibited osteoblast differentiation of hBMSCs in vitro. Moreover, Smad5 and RUNX2, which are the critical transcription factors in osteogenic differentiation, were predicted to be targets of miR-222-3p by bioinformatic analysis. Overexpression of miR-222-3p in hBMSCs significantly suppressed the protein levels of Smad5 and RUNX2, while inhibition of miR-222-3p increased their protein levels. Furthermore, inhibition of miR-222-3p increased phosphorylation of Smad1/5/8, which regulated the expression of osteogenic genes. Our findings suggest that suppression of miR-222-3p activity promoted osteogenic differentiation hBMSCs through regulating Smad5-RUNX2 signaling axis. PMID- 26809091 TI - Neurotrophic activity of jiadifenolide on neuronal precursor cells derived from human induced pluripotent stem cells. AB - Although jiadifenolide has been reported to neurotrophin-like activity in primary cultured rat cortical neurons, it is unknown on that of activity in human neurons. Thus, we aimed to assess neurotrophin-like activity by jiadifenolide in human neuronal cells. We analyzed neuronal precursor cells derived from human induced pluripotent stem cells for microtuble-associated-protein-2 expression by immunofluorescence and western blot, following jiadifenolide treatment. Jiadifenolide promoted dendrite outgrowth, facilitated growth, and prevented death in neuronal cells derived from human induced pluripotent stem cells. Interestingly, jiadifenolide also increased postsynaptic density-95 protein expression suggesting that jiadifenolide promotes neuronal maturation and post synaptic formation. We demonstrate for the first time that jiadifenolide exhibits neurotrophic effects on human neuronal precursor cells. PMID- 26809092 TI - PRELP (proline/arginine-rich end leucine-rich repeat protein) promotes osteoblastic differentiation of preosteoblastic MC3T3-E1 cells by regulating the beta-catenin pathway. AB - Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a collagen binding proteoglycan highly expressed in the developing bones. Recent studies indicated that PRELP could inhibit osteoclastogenesis as a NF-kappaB inhibitor. However, its role during osteoblast differentiation is still unclear. In this study, we confirmed that the expression of PRELP increased with the osteogenesis induction of preosteoblastic MC3T3-E1 cells. Down-regulation of PRELP expression by shRNA reduced ALP activity, mineralization and expression of osteogenic marker gene Runx2. Our microarray analysis data suggested that beta-catenin may act as a hub gene in the PRELP-mediated gene network. We validated furtherly that PRELP knockdown could inhibit the level of connexin43, a key regulator of osteoblast differentiation by affecting beta-catenin protein expression, and its nuclear translocation in MC3T3-E1 preosteoblasts. Therefore, this study established a new role of PRELP in modulating beta-catenin/connexin43 pathway and osteoblast differentiation. PMID- 26809093 TI - Neuroprotective effects of Wnt/beta-catenin signaling pathway against Abeta induced tau protein over-phosphorylation in PC12 cells. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disease, which is characterized by deposition of senile plaque (SP) and appearance of neurofibrillary tangles (NFT) in the cerebral cortex and hippocampus. SP is the accumulation of extracellular proteins/peptides, mainly consisting of the amyloid beta protein (Abeta), and the atrophy-degraded neuritis, microglias and astrocytes. NFT could be induced by the abnormal phosphorylation of Tau protein. Abeta may interfere with certain cell signal systems, which affects the level of Tau protein phosphorylation thus resulting in the forming of NFT. The present study explored the role of Wnt/beta-catenin pathway in the neurotoxic effect of Abeta25-35 on PC12 cells. Flow cytometry was employed to determine the effective sublethally dose of Abeta25-35, immunocytochemistry to decipher the intracellular distribution of microtubule associated protein-2 (MAP-2) and neurofilament H (NF H), western blotting to assess the protein abundance of phosphorylated tau in several sites and GSK-3. As a result, the Polymerization of and MAP-2 and NF-H induced by Abeta25-35 could be significantly inhibited by Wnt3a(40 ng/ml), however enhanced by Dkk1(100 ng/ml). Meanwhile, the protein abundance of phosphorylated tau in several sites is decreased by Wnt3a, but increased by Dkk1 significantly compared with the control group. In conclusion, Wnt/beta-catenin signaling pathway is involved in the neurotoxic effect of Abeta25-35 on PC12 cells. PMID- 26809094 TI - CaMKII in addition to MLCK contributes to phosphorylation of regulatory light chain in cardiomyocytes. AB - The aim was to identify kinase activities involved in the phosphorylation of regulatory light chain (RLC) in situ in cardiomyocytes. In electrically stimulated rat cardiomyocytes, phosphatase inhibition by calyculin A unmasked kinase activities evoking an increase of phosphorylated RLC (P-RLC) from about 16% to about 80% after 80 min. The phosphorylation rate in cardiomyocytes was reduced by about 40% by the myosin light chain kinase (MLCK) inhibitor, ML-7. In rat ventricular muscle strips, calyculin A induced a positive inotropic effect that correlated with P-RLC levels. The inotropic effect and P-RLC elevation were abolished by ML-7 treatment. The kinase activities phosphorylating RLC in cardiomyocytes were reduced by about 60% by the non-selective kinase inhibitor staurosporine and by about 50% by the calmodulin antagonist W7. W7 eliminated the inhibitory effect of ML-7, suggesting that the cardiac MLCK is Ca(2+)/calmodulin (CaM)-dependent. The CaM-dependent kinase II (CaMKII) inhibitor KN-93 attenuated the calyculin A-induced RLC phosphorylation by about 40%, indicating a contribution from CaMKII. The residual phosphorylation in the presence of W7 indicated that also CaM-independent kinase activities might contribute. RLC phosphorylation was insensitive to protein kinase C inhibition. In conclusion, in addition to MLCK, CaMKII phosphorylates RLC in cardiomyocytes. Involvement of other kinases cannot be excluded. PMID- 26809095 TI - Resveratrol-induced transcriptional up-regulation of ASMase (SMPD1) of human leukemia and cancer cells. AB - Resveratrol (RSV) is a plant-derived phytoalexin present in plants, whose pleiotropic effects for health benefits have been previously reported. Its anti cancer activity is among the current topics for novel cancer treatment. Here, effects of RSV on cell proliferation and the sphingolipid metabolism of K562, a human leukemia cell line, were analyzed. Some experiments were also performed in HCT116, a human colon cancer cell line. RSV inhibited cell proliferation of both cell lines. Increased cellular ceramide and decreased sphingomyelin and S1P by RSV were observed in RSV-treated K562 cells. Further analysis revealed that acid sphingomyelinase mRNA and enzyme activity levels were increased by RSV. Desipramine, a functional ASMase inhibitor, prevented RSV-induced ceramide increase. RSV increased ATF3, EGR1, EGR3 proteins and phosphorylated c-Jun and FOXO3. However, co-transfection using these transcription factor expression vectors and ASMase promoter reporter vector revealed positive effects of EGR1 and EGR3 but not others. Electrophoresis mobility shift assay (EMSA) and Chromatin immunoprecipitation (ChIP) assay demonstrated the direct binding of EGR1/3 transcription factors with ASMase 5'-promoter. These results indicate that increased EGR1/3 and ASMase expression play an important role in cellular ceramide increase by RSV treatment. PMID- 26809096 TI - Ovate family protein1 interaction with BLH3 regulates transition timing from vegetative to reproductive phase in Arabidopsis. AB - Three-Amino-acid-Loop-Extension(TALE) homeodomain transcription factor BLH3 regulates timing of transition from vegetative to reproductive phase. Previous preliminary results obtained using large-scale yeast two-hybrids indicate that BLH3 protein possibly interact with Ovate Family Proteins(OFPs) transcription co regulators. Nevertheless, it is uncertain whether OFP1-BLH3 complex is involved in regulation of timing of transition from vegetative to reproductive phase in Arabidopsis. The interaction between BLH3 and OFP1 was re-tested and verified by a yeast two-hybrid system. We found that the BLH3-OFP1 interaction was mainly mediated through the BLH3 homeodomain. Meanwhile, this interaction was further confirmed by bimolecular fluorescence complementation (BiFC) in vivo. Further, by establishing protoplast transient expression, we discovered that BLH3 acts as a transcriptional activator, whereas OFP1 functioned as a repressor. The interactions between OFP1 and BLH3 can reduce BLH3 transcriptional activity. The ofp1 mutant lines and blh3 mutant lines, OFP1 overexpress lines and BLH3 overexpress lines can both influence timing of transition from vegetative to reproductive phase. Furthermore, 35s:OFP1/blh3 plants exhibited flowering and leaf quantity similar to that of the wild-type controls. 35s:BLH3/ofp1 plants flowered earlier and had less leaves than wild-type controls, indicating that OFP1 protein might depend partially on BLH3 in its function to regulate the timing of transition from vegetative to reproductive phase. These results support our assumption that, by interacting with OFP1, BLH3 forms a functional protein complex that controls timing of progression from vegetative to reproductive phase, and OFP1 might negatively regulate BLH3 or the BLH-KNOX complex, an important interaction for sustaining the normal transition from vegetative to reproductive phase. PMID- 26809097 TI - Identification of moisture content in tobacco plant leaves using outlier sample eliminating algorithms and hyperspectral data. AB - Fast identification of moisture content in tobacco plant leaves plays a key role in the tobacco cultivation industry and benefits the management of tobacco plant in the farm. In order to identify moisture content of tobacco plant leaves in a fast and nondestructive way, a method involving Mahalanobis distance coupled with Monte Carlo cross validation(MD-MCCV) was proposed to eliminate outlier sample in this study. The hyperspectral data of 200 tobacco plant leaf samples of 20 moisture gradients were obtained using FieldSpc((r)) 3 spectrometer. Savitzky Golay smoothing(SG), roughness penalty smoothing(RPS), kernel smoothing(KS) and median smoothing(MS) were used to preprocess the raw spectra. In addition, Mahalanobis distance(MD), Monte Carlo cross validation(MCCV) and Mahalanobis distance coupled to Monte Carlo cross validation(MD-MCCV) were applied to select the outlier sample of the raw spectrum and four smoothing preprocessing spectra. Successive projections algorithm (SPA) was used to extract the most influential wavelengths. Multiple Linear Regression (MLR) was applied to build the prediction models based on preprocessed spectra feature in characteristic wavelengths. The results showed that the preferably four prediction model were MD-MCCV-SG (Rp(2) = 0.8401 and RMSEP = 0.1355), MD-MCCV-RPS (Rp(2) = 0.8030 and RMSEP = 0.1274), MD MCCV-KS (Rp(2) = 0.8117 and RMSEP = 0.1433), MD-MCCV-MS (Rp(2) = 0.9132 and RMSEP = 0.1162). MD-MCCV algorithm performed best among MD algorithm, MCCV algorithm and the method without sample pretreatment algorithm in the eliminating outlier sample from 20 different moisture gradients of tobacco plant leaves and MD-MCCV can be used to eliminate outlier sample in the spectral preprocessing. PMID- 26809098 TI - A soluble form of the interleukin-6 family signal transducer gp130 is dimerized via a C-terminal disulfide bridge resulting from alternative mRNA splicing. AB - Interleukin-6 (IL-6) signaling can be divided into classic signaling (via the membrane-bound IL-6 receptor, IL-6R) and trans-signaling (via the soluble IL-6R, sIL-6R), and both modes of signaling activate cells via a homodimer of the ubiquitously expressed beta-receptor glycoprotein 130 (gp130). IL-6 trans signaling is responsible for most of the pro-inflammatory activities of IL-6 and plays a role in many inflammatory diseases including inflammation-driven cancers. IL-6 trans-signaling can be selectively inhibited by soluble forms of gp130. To date, three forms of sgp130 (full-length sgp130, sgp130-RAPS and sgp130-E10) with different molecular weight have been described, which originate from alternative splicing or alternative polyadenylation of the gp130 mRNA. All these proteins are capable of blocking signaling of the IL-6/sIL-6R complex, albeit with different efficacy. The full length form of sgp130 comprises the domains D1 to D6 and a short unique C-terminus which arises from alternative splicing. In the present study, we analyze the role of a unique cysteine residue (Cys-628) within this C terminus, which is contained neither in the membrane-bound gp130 nor in the two other sgp130 forms. Full-length sgp130 can form a disulfide-linked dimer via this cysteine residue. These natural sgp130 dimers are absent under reducing conditions or in a sgp130 C628A mutant. Although the disulfide-dimerized sgp130 represents only a small fraction of the total amount of sgp130 and, thus, may appear to be dispensable for the global inhibitory activities of sgp130 in the circulation, it may represent a further possibility to modulate gradients of sgp130 with different properties depending on the local redox potential in a cell or tissue-dependent manner. PMID- 26809099 TI - Detection of overlapping protein complexes in gene expression, phenotype and pathways of Saccharomyces cerevisiae using Prorank based Fuzzy algorithm. AB - Proteins show their functional activity by interacting with other proteins and forms protein complexes since it is playing an important role in cellular organization and function. To understand the higher order protein organization, overlapping is an important step towards unveiling functional and evolutionary mechanisms behind biological networks. Most of the clustering algorithms do not consider the weighted as well as overlapping complexes. In this research, Prorank based Fuzzy algorithm has been proposed to find the overlapping protein complexes. The Fuzzy detection algorithm is incorporated in the Prorank algorithm after ranking step to find the overlapping community. The proposed algorithm executes in an iterative manner to compute the probability of robust clusters. The proposed and the existing algorithms were tested on different datasets such as PPI-D1, PPI-D2, Collins, DIP, Krogan Core and Krogan-Extended, gene expression such as GSE7645, GSE22269, GSE26923, pathways such as Meiosis, MAPK, Cell Cycle, phenotypes such as Yeast Heterogeneous and Yeast Homogeneous datasets. The experimental results show that the proposed algorithm predicts protein complexes with better accuracy compared to other state of art algorithms. PMID- 26809100 TI - Characterization of bovine A20 gene: Expression mediated by NF-kappaB pathway in MDBK cells infected with bovine viral diarrhea virus-1. AB - Cytokine production for immunological process is tightly regulated at the transcriptional and posttranscriptional levels. The NF-kappaB signaling pathway maintains immune homeostasis in the cell through the participation of molecules such as A20 (TNFAIP3), which is a key regulatory factor in the immune response, hematopoietic differentiation, and immunomodulation. Although A20 has been identified in mammals, and despite recent efforts to identify A20 members in other higher vertebrates, relatively little is known about the composition of this regulator in other classes of vertebrates, particularly for bovines. In this study, the genetic context of bovine A20 was explored and compared against homologous genes in the human, mouse, chicken, dog, and zebrafish chromosomes. Through in silico analysis, several regions of interest were found conserved between even phylogenetically distant species. Additionally, a protein-deduced sequence of bovine A20 evidenced many conserved domains in humans and mice. Furthermore, all potential amino acid residues implicated in the active site of A20 were conserved. Finally, bovine A20 mRNA expression as mediated by the bovine viral diarrhea virus and poly (I:C) was evaluated. These analyses evidenced a strong fold increase in A20 expression following virus exposure, a phenomenon blocked by a pharmacological NF-kappaB inhibitor (BAY 117085). Interestingly, A20 mRNA had a half-life of only 32min, likely due to adenylate- and uridylate-rich elements in the 3'-untranslated region. Collectively, these data identify bovine A20 as a regulator of immune marker expression. Finally, this is the first report to find the bovine viral diarrhea virus modulating bovine A20 activation through the NF-kappaB pathway. PMID- 26809101 TI - Repetitive transpositions of mitochondrial DNA sequences to the nucleus during the radiation of horseshoe bats (Rhinolophus, Chiroptera). AB - Transposition of mitochondrial DNA into the nucleus, which gives rise to nuclear mitochondrial DNAs (NUMTs), has been well documented in eukaryotes. However, very few studies have assessed the frequency of these transpositions during the evolutionary history of a specific taxonomic group. Here we used the horseshoe bats (Rhinolophus) as a case study to determine the frequency and relative timing of nuclear transfers of mitochondrial control region sequences. For this, phylogenetic and coalescent analyzes were performed on NUMTs and authentic mtDNA sequences generated from eight horseshoe bat species. Our results suggest at least three independent transpositions, including two ancient and one more recent, during the evolutionary history of Rhinolophus. The two ancient transpositions are represented by the NUMT-1 and -2 clades, with each clade consisting of NUMTs from almost all studied species but originating from different portions of the mtDNA genome. Furthermore, estimates of the most recent common ancestor for each clade corresponded to the time of the initial diversification of this genus. The recent transposition is represented by NUMT-3, which was discovered only in a specific subgroup of Rhinolophus and exhibited a close relationship to its mitochondrial counterpart. Our similarity searches of mtDNA in the R. ferrumequinum genome confirmed the presence of NUMT-1 and NUMT-2 clade sequences and, for the first time, assessed the extent of NUMTs in a bat genome. To our knowledge, this is the first study to report on the frequency of transpositions of mtDNA occurring before the common ancestry of a genus. PMID- 26809102 TI - Cobalt(III)-Mediated Permanent and Stable Immobilization of Histidine-Tagged Proteins on NTA-Functionalized Surfaces. AB - We present the cobalt(III)-mediated interaction between polyhistidine (His) tagged proteins and nitrilotriacetic acid (NTA)-modified surfaces as a general approach for a permanent, oriented, and specific protein immobilization. In this approach, we first form the well-established Co(2+) -mediated interaction between NTA and His-tagged proteins and subsequently oxidize the Co(2+) center in the complex to Co(3+) . Unlike conventionally used Ni(2+) - or Co(2+) -mediated immobilization, the resulting Co(3+) -mediated immobilization is resistant toward strong ligands, such as imidazole and ethylenediaminetetraacetic acid (EDTA), and washing off over time because of the high thermodynamic and kinetic stability of the Co(3+) complex. This immobilization method is compatible with a wide variety of surface coatings, including silane self-assembled monolayers (SAMs) on glass, thiol SAMs on gold surfaces, and supported lipid bilayers. Furthermore, once the cobalt center has been oxidized, it becomes inert toward reducing agents, specific and unspecific interactions, so that it can be used to orthogonally functionalize surfaces with multiple proteins. Overall, the large number of available His-tagged proteins and materials with NTA groups make the Co(3+) mediated interaction an attractive and widely applicable platform for protein immobilization. PMID- 26809103 TI - Risk of chemotherapy-induced neutropenic complications when treating patients with non-Hodgkin lymphoma. AB - INTRODUCTION: Myelosuppression induced by cancer chemotherapy is associated with considerable morbidity and mortality. Febrile neutropenia (FN) represents an oncologic emergency requiring immediate evaluation and treatment. Resulting chemotherapy dose reductions or delays may compromise disease control and survival. While non-Hodgkin lymphoma (NHL) represents a potentially curable malignancy, there are limited data on the risk of neutropenic complications. This review represents a systematic search and evidence summary of neutropenic complications reported in randomized controlled trials (RCTs) published over the past decade in adults with NHL receiving myelosuppressive chemotherapy. AREAS COVERED: Data captured include the chemotherapy regimen and dosing, the type of NHL, sample size, myeloid growth factor (MGF) use, and myelosuppression including FN and severe neutropenia and infection. EXPERT OPINION: Rates of neutropenic complications for commonly utilized chemotherapy regimens vary considerably across studies with FN reported in only one-fourth of study arms. Further challenges in interpreting reported rates are the variable and inconsistent use of MGF support and little or no information on delivered chemotherapy dose intensity. Considerable change in regimens, study populations and reporting of neutropenic events as well as the use of MGF was observed over the decade of RCTs reported. Complete and accurate reporting of treatment-related toxicities in patients receiving cancer chemotherapy is essential in both clinical trials and clinical practice. PMID- 26809104 TI - Development of a highly transparent superamphiphobic plastic sheet by nanoparticle and chemical coating. AB - A highly transparent superamphiphobic plastic sheet was developed. The plastic sheet polymethyl methacrylate (PMMA) was spin-coated on a glass substrate. Synthesized silica nanoparticles were sprayed on PMMA, followed by fluorosilane drop-coating. The results of contact angle measurements show that the developed PMMA sheet has superamphiphobic properties with high advancing contact angles for water (154 degrees ), toluene (139 degrees ), and silicone oil (132.9 degrees ). The amphiphobicity of the plastic sheet can be tuned by the surface coverage of the silica nanoparticles distributed on the PMMA surface. The surface coverage of the nanoparticles on our PMMA sheet is about 20%, and it agrees with our contact angle calculations for the sheet with and without nanoparticles. PMID- 26809105 TI - Polyaniline coated membranes for effective separation of oil-in-water emulsions. AB - Polyaniline (PANI) decorated commercial filtration membranes, such as stainless steel meshes (SSMs) with 5MUm pore size and polyvinylidene fluoride (PVDF) membranes with 2-0.22MUm pore sizes, were fabricated by a simple one-step dilute polymerization at low temperature. Lots of short PANI nanofibers were firmly and uniformly coated onto the membrane surfaces, forming rough micro- and nanoscale structures and leading to underwater superoleophobicity with low oil-adhesion characteristic. Furthermore, we systematically studied the effect of pore size and pressure difference on oil-water separation ability of the obtained membranes. It was found that the PANI-modified SSMs with 5MUm pore size were suitable for the separation of non-surfactant emulsions with water fluxes of more than 1000Lm(-2)h(-1) under gravity only. The PANI-modified PVDF membranes were used for the effective separation of surfactant-stabilized emulsions with water fluxes up to 3000Lm(-2)h(-1) for 2MUm pore size under 0.1bar or 0.22MUm pore size under 0.6bar. In addition, the superhydrophilic membranes with PANI coatings were demonstrated for high oil rejection, stable underwater superoleophobic properties after ultrasonic treatment and immersing in oils and various harsh conditions, and high and steady water permeation flux after several cycles. PMID- 26809106 TI - Adsorption of the intrinsically disordered saliva protein histatin 5 to silica surfaces. A Monte Carlo simulation and ellipsometry study. AB - HYPOTHESIS: The adsorption of histatin 5 to hydrophilic silica surfaces is governed by electrostatic attractive forces between the positive protein and the negative surface. Hence pH and ionic strength control the adsorbed amount, which can be described by coarse-grained Monte Carlo simulations accounting for electrostatic forces and charge regulation of the protein. EXPERIMENTS: The amount of histatin 5 adsorbed to hydrophilic silica surfaces at different pH and ionic strengths was measured using null ellipsometry. The results were compared with coarse-grained Monte Carlo simulations of a single histatin 5 molecule and a surface with a fixed, smeared charge set according to experimental values for silica. The Langmuir isotherm was used to calculate the surface coverage from the simulation results. The effect of charge regulation of the protein was investigated. FINDINGS: Even though electrostatic attractive forces are important for the investigated system, a non-electrostatic short-ranged attraction with a strength of about 2.9kBT per amino acid was needed in the simulations to get surface coverages close to experimental values. The importance of electrostatics increases with increasing pH. Charge regulation of the protein affected the results from the simulations only at high surface charge and low ionic strength. PMID- 26809107 TI - Ag@polypyrrole: A highly efficient nanocatalyst for the N-alkylation of amines using alcohols. AB - We have synthesized Ag@polypyrrole nanomaterial by dispersing ultrafine silver nanoparticles (Ag NPs) over the organic polymer polypyrrole. The Ag@polypyrrole material has been characterized by powder X-ray diffraction (PXRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), electron paramagnetic resonance (EPR), Fourier transform infrared (FT-IR), ultraviolet visible absorption (UV-vis) and atomic adsorption spectroscopy (AAS), and thermogravimetric analysis (TGA). The XRD pattern suggested the cubic crystalline phase of Ag NPs in Ag@polypyrrole. TEM image analysis revealed that silver nanoparticles are highly dispersed in the polymer matrix. The Ag@polypyrrole acts as an efficient and versatile heterogeneous nanocatalyst in the N-alkylation of amines using alcohols. The catalyst can be easily prepared, highly robust and reused several times without decrease in its catalytic activity. PMID- 26809108 TI - Childhood Psychosocial Cumulative Risks and Carotid Intima-Media Thickness in Adulthood: The Cardiovascular Risk in Young Finns Study. AB - OBJECTIVE: Adverse experiences in childhood may influence cardiovascular risk in adulthood. We examined the prospective associations between types of psychosocial adversity and having multiple adversities (e.g., cumulative risk) with carotid intima-media thickness (IMT) and its progression among young adults. Higher cumulative risk score in childhood was expected to be associated with higher IMT and its progression. METHODS: Participants were 2265 men and women (age range, 24 39 years in 2001) from the ongoing Cardiovascular Risk in Young Finns study whose carotid IMTs were measured in 2001 and 2007. A cumulative psychosocial risk score, assessed at the study baseline in 1980, was derived from four separate aspects of the childhood environment that may impose risk (childhood stressful life events, parental health behavior family, socioeconomic status, and childhood emotional environment). RESULTS: The cumulative risk score was associated with higher IMT in 2007 (b = 0.004, standard error [SE] = 0.001, p < .001) and increased IMT progression from 2001 to 2007 (b = 0.003, SE = 0.001, p = .001). The associations were robust to adjustment for conventional cardiovascular risk factors in childhood and adulthood, including adulthood health behavior, adulthood socioeconomic status, and depressive symptoms. Among the individual childhood psychosocial risk categories, having more stressful life events was associated with higher IMT in 2001 (b = 0.007, SE = 0.003, p = .016) and poorer parental health behavior predicted higher IMT in 2007 (b = 0.004, SE = 0.002, p = .031) after adjustment for age, sex, and childhood cardiovascular risk factors. CONCLUSIONS: Early life psychosocial environment influences cardiovascular risk later in life, and considering cumulative childhood risk factors may be more informative than individual factors in predicting progression of preclinical atherosclerosis in adulthood. PMID- 26809109 TI - Early Life Family Conflict, Social Interactions, and Carotid Artery Intima-Media Thickness in Adulthood. AB - OBJECTIVE: Conflict in early life family environments is known to affect psychosocial functioning and coping styles into adulthood and is reported to negatively affect access to psychosocial resources that are critical to the management of stress. However, it remains unknown whether early life family conflict similarly affects subclinical cardiovascular disease (CVD) in adulthood. We predicted that family conflict in early life would be associated with greater mean intima-media thickness (IMT), a subclinical marker of CVD risk, in adulthood. METHODS: Data were collected in a community sample of 503 adults (47.4 % male, mean [standard deviation] age = 42.8 [7.3] years). Associations between family conflict in early life with IMT (assessed using B-mode ultrasound) in adulthood were examined using regression analysis. We also tested for indirect effects of early life family conflict on mean IMT through ecological momentary assessment reports of social interactions, diversity of social roles, and perceived social support. RESULTS: Linear regression analyses adjusted for demographics and physiological risk factors showed conflict in early life associated with greater mean IMT (beta = 0.08, t(447) = 2.13, p = .034, R = 0.46). Early life conflict was significantly related to diversity of social roles, perceived social support, and ecological momentary assessment reports of pleasant and social conflict interactions. Significant indirect effects of early life conflict on mean IMT were observed through fewer pleasant social interactions and more frequent social conflict interactions in adulthood (beta = 0.001 [95% confidence interval = 0.0001-0.0014] and beta = 0.001 [95% confidence interval = 0.0002-0.0015], respectively). CONCLUSIONS: These findings provide initial evidence that family conflict in early life heightens CVD risk in adulthood, in part by shaping the quality of adulthood social interactions. PMID- 26809110 TI - Pollination of lark daisy on roadsides declines as traffic speed increases along an Amazonian highway. AB - Ecological disturbances caused by roadways have previously been reported, but traffic speed has not been addressed. We investigate effects of traffic speed on pollination of Centratherum punctatum (Asteraceae) along an Amazonian highway roadside. We hypothesised that frequency of flower visitors, duration of single visits and pollen deposition on stigmas will vary negatively as traffic speed increases. After measuring vehicle velocities, we classified three road sections as low-, mid- and high-velocity traffic. The main pollinator bee, Augochlora sp., visited C. punctatum inflorescences with decreasing frequency from low- to high velocity roadside sections, whereas the nectar thief butterflies did the opposite. Duration of single visits by bees and butterflies was shorter, and arrival of pollen on C. punctatum stigmas was lower, in high- than in low velocity roadside. Air turbulence due to passing vehicles increases with velocity and disturbed the flower visitors. Overall, results support that traffic velocity negatively affects foraging of flower visitors and the pollination of C. punctatum on roadsides. PMID- 26809111 TI - Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial. AB - BACKGROUND & AIMS: Transarterial chemoembolization with doxorubicin-eluting beads (DC Bead(r); DEB-TACE) is effective in patients with Barcelona clinic liver cancer stage B hepatocellular carcinoma (HCC). The multikinase inhibitor sorafenib enhances overall survival (OS) and time-to-tumor progression (TTP) in patients with advanced HCC. This exploratory phase II trial tested the efficacy and safety of DEB-TACE plus sorafenib in patients with intermediate stage HCC. METHODS: Patients with intermediate stage multinodular HCC without macrovascular invasion (MVI) or extrahepatic spread (EHS) were randomized 1:1 to DEB-TACE (150 mg doxorubicin) plus sorafenib 400 mg twice daily or placebo. The primary endpoint was TTP by blinded central review. Secondary endpoints included time to MVI/EHS, OS, overall response rate (ORR) using modified response evaluation criteria in solid tumors, disease control rate (DCR), time to unTACEable progression (TTUP), and safety. RESULTS: Of 307 patients randomized, 154 received sorafenib and 153 received placebo. Median TTP for subjects receiving sorafenib plus DEB-TACE or placebo plus DEB-TACE was similar (169 vs. 166 days, respectively; hazard ratio (HR) 0.797, p=0.072). Median time to MVI/EHS (HR 0.621, p=0.076) and OS (HR 0.898, p=0.29) had not been reached. The ORRs for patients in the sorafenib and placebo groups with post-baseline scans were 55.9% and 41.3%, respectively, and the DCRs were 89.2% and 76.1%, respectively. TTUP was lower with sorafenib than with placebo (HR 1.586; 95% confidence intervals, 1.200-2.096; median 95 vs. 224 days). No unexpected adverse events related to sorafenib were observed. CONCLUSION: Sorafenib plus DEB-TACE was technically feasible, but the combination did not improve TTP in a clinically meaningful manner compared with DEB-TACE alone. PMID- 26809112 TI - Increasing prevalence of cirrhosis among U.S. adults aware or unaware of their chronic hepatitis C virus infection. AB - BACKGROUND & AIMS: Cirrhosis from hepatitis C virus (HCV) infection is a major cause of end-stage liver disease and hepatocellular carcinoma worldwide. We determine the prevalence of cirrhosis among HCV-infected American adults including those unaware of their infection. METHODS: Using the National Health and Nutrition Examination Survey (NHANES) data, we identified participants aged ?20 years with detectable serum HCV RNA. The prevalence of advanced fibrosis and cirrhosis was determined for eras 1 (1988-94), 2 (1999-2006) and 3 (2007-2012) by using FIB-4 >3.25 and APRI >2.0, respectively. RESULTS: Out of 52,644 NHANES examinees, 49,429 were tested for HCV, of whom 725 met the inclusion criteria (positive HCV RNA with available data for FIB-4 and APRI). Based on APRI, 6.6% (95% confidence interval [CI]: 2.2-11.0) of HCV-infected adults in era 1, 7.6% (95% CI: 3.4-11.8) in era 2 and 17.0% (95% CI: 8.0-26.0) in era 3 had cirrhosis. In the multivariable regression analysis, this era effect was attributable to increasing age (odds ratio [OR]:1.04, 95% CI: 1.02-1.07), diabetes (OR: 2.33, 95% CI: 1.01-5.40) and obesity (OR: 2.96, 95% CI: 1.15-7.57). Cirrhosis was as common among respondents who were unaware of their infection as those who were aware (both 11%). Results were identical when FIB-4 was used. CONCLUSIONS: Among HCV infected American adults, the proportion with cirrhosis has increased rapidly. Cirrhosis prevalence remains high in individuals unaware of their HCV infection. These data highlight the urgency for HCV screening regardless of symptoms, systematic assessment for liver fibrosis in those with HCV infection and institution of antivirals to prevent advanced liver disease. LAY SUMMARY: Chronic hepatitis C virus (HCV) infection is a major cause of cirrhosis, creating a large public health burden. Based on the U.S. National Health and Nutrition Examination Survey sample, we found the proportion of patients with cirrhosis among Americans with HCV infection increased from 6.6% to 17.0% over the past two decades. Patients who were unaware of their infection were just as likely to have cirrhosis as those who knew about their infection, which highlights the need for screening and treatment for HCV at the population level. PMID- 26809113 TI - IL-23 prevents IL-13-dependent tissue repair associated with Ly6C(lo) monocytes in Entamoeba histolytica-induced liver damage. AB - BACKGROUND & AIMS: The IL-23/IL-17 axis plays an important role in the pathogenesis of autoimmune diseases and the pathological consequences of infection. We previously showed that immunopathologic mechanisms mediated by inflammatory monocytes underlie the severe focal liver damage induced by the protozoan parasite, Entamoeba histolytica. Here, we analyze the contribution of the IL-23/IL-17 axis to the induction and subsequent recovery from parasite induced liver damage. METHODS: IL-23p19(-/-), IL-17A/F(-/-), CCR2(-/-), and wild type (WT) mice were intra-hepatically infected with E. histolytica trophozoites and disease onset and recovery were analyzed by magnetic resonance imaging. Liver specific gene and protein expression during infection was examined by qPCR, microarray, FACS analysis and immunohistochemistry. Immuno-depletion and substitution experiments were performed in IL-23p19(-/-) and WT mice to investigate the role of IL-13 in disease outcome. RESULTS: Liver damage in infected IL-23p19(-/-), IL-17A/F(-/-), and CCR2(-/-) mice was strongly attenuated compared with that in WT mice. IL-23p19(-/-) mice showed reduced accumulation of IL-17 and CCL2 mRNA and proteins. Increased numbers of IL-13-producing CD11b(+)Ly6C(lo) monocytes were associated with disease attenuation in IL-23p19( /-) mice. Immuno-depletion of IL-13 in IL-23p19(-/-) mice reversed this attenuation and treatment of infected WT mice with an IL-13/anti-IL-13-mAb complex supported liver recovery. CONCLUSIONS: The IL-23/IL-17 axis plays a critical role in the immunopathology of hepatic amebiasis. IL-13 secreted by CD11b(+)Ly6C(lo) monocytes may be associated with recovery from liver damage. An IL-13/anti-IL13-mAb complex mimics this function, suggesting a novel therapeutic option to support tissue healing after liver damage. PMID- 26809114 TI - Myo-pericarditis secondary to ledipasvir-sofosbuvir therapy. PMID- 26809116 TI - Value of a gene signature assay in patients with early breast cancer and intermediate risk: a single institution retrospective study. AB - Purpose In daily clinical practice, the indication for adjuvant chemotherapy (CT) is relatively easy to make in patients with early hormone-receptor-positive (HR+) breast cancer with either very poor or very good clinicopathological prognostic variables. However, this decision is much more difficult in patients with intermediate clinicopathological prognostic variables. Here, we evaluate the value of a gene-expression profile identified by the Prosigna gene signature assay in guiding treatment decision-making in patients with these intermediate features. Methods A consecutive cohort of 577 HR + breast cancer patients surgically treated in a single institution between January 2012 and December 2012 was evaluated. From this population, pre- and post-menopausal patients with intermediate prognosis clinicopathological variables were identified and indication of adjuvant CT in these patients was recorded. The gene signature assay was performed retrospectively in this intermediate risk group. Descriptive statistics are presented. Results Among 96 intermediate-risk patients, 64 postmenopausal patients underwent gene signature testing. Subtype distribution was as follows: Luminal A (N = 33; 51.6%), Luminal B (N = 31; 48.4%). Risk of recurrence (ROR) distribution was as follows: ROR-low (n = 16; 25%); ROR intermediate (N = 26; 40.6%); and ROR-high (N = 22; 34.4%). CT was subsequently administered in 18.7%, 53.8% and 59.0% of the ROR-low, ROR-intermediate and ROR high groups, respectively. With the use of the gene signature assay, 59.4% of the intermediate cases were re-classified to either ROR-low or ROR-high risk categories. In the ROR-intermediate group, 11/26 patients (42.3%) had Luminal A and 15/26 (57.7%) had Luminal B. Due to follow-up time constraints, no patient outcome results were evaluated. Conclusion The gene signature assay provides clinically useful information and improved treatment decision-making in patients with intermediate risk based on clinicopathological factors. Determining the patient's intrinsic subtype and ROR can aid clinicians in deciding whether CT should be indicated. PMID- 26809115 TI - Magnet(r) Hospital Recognition Linked to Lower Central Line-Associated Bloodstream Infection Rates. AB - Central-line-associated bloodstream infections (CLABSI) are among the deadliest heathcare-associated infections, with an estimated 12-25% mortality rate. In 2014, the Centers for Medicare and Medicaid Services (CMS) began to penalize hospitals for poor performance with respect to selected hospital-acquired conditions, including CLABSI. A structural factor associated with high-quality nursing care and better patient outcomes is The Magnet Recognition Program(r). The purpose of this study was to explore the relationship between Magnet status and hospital CLABSI rates. We used propensity score matching to match Magnet and non-Magnet hospitals with similar hospital characteristics. In a matched sample of 291 Magnet hospitals and 291 non-Magnet hospitals, logistic regression models were used to examine whether there was a link between Magnet status and CLABSI rates. Both before and after matching, Magnet hospital status was associated with better (lower than the national average) CLABSI rates (OR = 1.60, 95%CI: 1.10, 2.33 after matching). While established programs such as Magnet recognition are consistently correlated with high-quality nursing work environments and positive patient outcomes, additional research is needed to determine whether Magnet designation produces positive patient outcomes or rewards existing excellence. PMID- 26809118 TI - Formation and Reactivity of Organo-Functionalized Tin Selenide Clusters. AB - Reactions of R(1) SnCl3 (R(1) =CMe2 CH2 C(O)Me) with (SiMe3 )2 Se yield a series of organo-functionalized tin selenide clusters, [(SnR(1) )2 SeCl4 ] (1), [(SnR(1) )2 Se2 Cl2 ] (2), [(SnR(1) )3 Se4 Cl] (3), and [(SnR(1) )4 Se6 ] (4), depending on the solvent and ratio of the reactants used. NMR experiments clearly suggest a stepwise formation of 1 through 4 by subsequent condensation steps with the concomitant release of Me3 SiCl. Furthermore, addition of hydrazines to the keto functionalized clusters leads to the formation of hydrazone derivatives, [(Sn2 (MU-R(3) )(MU-Se)Cl4 ] (5, R(3) =[CMe2 CH2 CMe(NH)]2 ), [(SnR(2) )3 Se4 Cl] (6, R(2) =CMe2 CH2 C(NNH2 )Me), [(SnR(4) )3 Se4 ][SnCl3 ] (7, R(4) =CMe2 CH2 C(NNHPh)Me), [(SnR(2) )4 Se6 ] (8), and [(SnR(4) )4 Se6 ] (9). Upon treatment of 4 with [Cu(PPh3 )3 Cl] and excess (SiMe3 )2 Se, the cluster fragments to form [(R(1) Sn)2 Se2 (CuPPh3 )2 Se2 ] (10), the first discrete Sn/Se/Cu cluster compound reported in the literature. The derivatization reactions indicate fundamental differences between organotin sulfide and organotin selenide chemistry. PMID- 26809117 TI - Genomic Comparative Study of Bovine Mastitis Escherichia coli. AB - Escherichia coli, one of the main causative agents of bovine mastitis, is responsible for significant losses on dairy farms. In order to better understand the pathogenicity of E. coli mastitis, an accurate characterization of E. coli strains isolated from mastitis cases is required. By using phylogenetic analyses and whole genome comparison of 5 currently available mastitis E. coli genome sequences, we searched for genotypic traits specific for mastitis isolates. Our data confirm that there is a bias in the distribution of mastitis isolates in the different phylogenetic groups of the E. coli species, with the majority of strains belonging to phylogenetic groups A and B1. An interesting feature is that clustering of strains based on their accessory genome is very similar to that obtained using the core genome. This finding illustrates the fact that phenotypic properties of strains from different phylogroups are likely to be different. As a consequence, it is possible that different strategies could be used by mastitis isolates of different phylogroups to trigger mastitis. Our results indicate that mastitis E. coli isolates analyzed in this study carry very few of the virulence genes described in other pathogenic E. coli strains. A more detailed analysis of the presence/absence of genes involved in LPS synthesis, iron acquisition and type 6 secretion systems did not uncover specific properties of mastitis isolates. Altogether, these results indicate that mastitis E. coli isolates are rather characterized by a lack of bona fide currently described virulence genes. PMID- 26809119 TI - Wolbachia in European Populations of the Invasive Pest Drosophila suzukii: Regional Variation in Infection Frequencies. AB - The invasive pest Drosophila suzukii is characterized by a specific fresh-fruit targeting behavior and has quickly become a menace for the fruit economy of newly infested North American and European regions. D. suzukii carries a strain of the endosymbiotic bacterium Wolbachia, named wSuz, which has a low infection frequency and no reproductive manipulation capabilities in American populations of D. suzukii. To further understand the nature of wSuz biology and assess its utility as a tool for controlling this pest's populations, we investigated the prevalence of Wolbachia in 23 European D. suzukii populations, and compared our results with those available in American populations. Our data showed a highly variable infection frequency with a mean prevalence of 46%, which is significantly higher than the 17% found in American populations. Based on Multilocus Sequence Typing analysis, a single wSuz strain was diagnosed in all European populations of D. suzukii. In agreement with American data, we found no evidence of cytoplasmic incompatibility induced by wSuz. These findings raise two questions: a) why Wolbachia is maintained in field populations of D. suzukii and b) what are the selective forces responsible for the variation in prevalence within populations, particularly between European and American continents? Our results provide new insights into the D. suzukii-Wolbachia association and highlight regional variations that await further investigation and that should be taken into account for using Wolbachia-based pest management programs. PMID- 26809120 TI - Mitochondrial response to the BCKDK-deficiency: Some clues to understand the positive dietary response in this form of autism. AB - Mutations on the mitochondrial-expressed Branched Chain alpha-Keto acid Dehydrogenase Kinase (BCKDK) gene have been recently associated with a novel dietary-treatable form of autism. But, being a mitochondrial metabolism disease, little is known about the impact on mitochondrial performance. Here, we analyze the mitochondrial response to the BCKDK-deficiency in patient's primary fibroblasts by measuring bioenergetics, ultra-structural and dynamic parameters. A two-fold increase in superoxide anion production, together with a reduction in ATP-linked respiration and intracellular ATP levels (down to 60%) detected in mutants fibroblasts point to a general bioenergetics depletion that could affect the mitochondrial dynamics and cell fate. Ultrastructure analysis of BCKDK deficient fibroblasts shows an increased number of elongated mitochondria, apparently associated with changes in the mediator of inner mitochondria membrane fusion, GTPase OPA1 forms, and in the outer mitochondrial membrane, mitofusin 2/MFN2. Our data support a possible hyperfusion response of BCKDK-deficient mitochondria to stress. Cellular fate also seems to be affected as these fibroblasts show an altered proportion of the cells on G0/G1 and G2/M phases. Knockdown of BCKDK gene in control fibroblasts recapitulates most of these features. Same BCKDK-knockdown in a MSUD patient fibroblasts unmasks the direct involvement of the accelerated BCAAs catabolism in the mitochondrial dysfunction. All these data give us a clue to understand the positive dietary response to an overload of branched-chain amino acids. We hypothesize that a combination of the current therapeutic option with a protocol that considers the oxidative damage and energy expenditure, addressing the patients' individuality, might be useful for the physicians. PMID- 26809121 TI - EF4 disengages the peptidyl-tRNA CCA end and facilitates back-translocation on the 70S ribosome. AB - EF4 catalyzes tRNA back-translocation through an unknown mechanism. We report cryo-EM structures of Escherichia coli EF4 in post- and pretranslocational ribosomes (Post- and Pre-EF4) at 3.7- and 3.2-A resolution, respectively. In Post EF4, peptidyl-tRNA occupies the peptidyl (P) site, but the interaction between its CCA end and the P loop is disrupted. In Pre-EF4, the peptidyl-tRNA assumes a unique position near the aminoacyl (A) site, denoted the A site/EF4 bound (A/4) site, with a large displacement at its acceptor arm. Mutagenesis analyses suggest that a specific region in the EF4 C-terminal domain (CTD) interferes with base pairing between the peptidyl-tRNA 3'-CCA and the P loop, whereas the EF4 CTD enhances peptidyl-tRNA interaction at the A/4 site. Therefore, EF4 induces back translocation by disengaging the tRNA's CCA end from the peptidyl transferase center of the translating ribosome. PMID- 26809122 TI - Overexpression of Anti-Mullerian Hormone Disrupts Gonadal Sex Differentiation, Blocks Sex Hormone Synthesis, and Supports Cell Autonomous Sex Development in the Chicken. AB - The primary role of Anti-Mullerian hormone (AMH) during mammalian development is the regression of Mullerian ducts in males. This highly conserved function is retained in birds and is supported by the high levels of AMH expression in developing testes. Mammalian AMH expression is regulated by a combination of transcription factors, the most important being Sry-type high-mobility-group box transcription factor-9 (SOX9). In the chicken embryo, however, AMH mRNA expression precedes that of SOX9, leading to the view that AMH may play a more central role in avian testicular development. To define its role in chicken gonadal development, AMH was overexpressed using the RCASBP viral vector. AMH caused the gonads of both sexes to develop as small and undeveloped structures at both embryonic and adult stages. Molecular analysis revealed that although female gonads developed testis-like cords, gonads lacked Sertoli cells and were incapable of steroidogenesis. A similar gonadal phenotype was also observed in males, with a complete loss of both Sertoli cells, disrupted SOX9 expression and gonadal steroidogenesis. At sexual maturity both sexes showed a female external phenotype but retained sexually dimorphic body weights that matched their genetic sexes. These data suggest that AMH does not operate as an early testis activator in the chicken but can affect downstream events, such as sex steroid hormone production. In addition, this study provides a unique opportunity to assess chicken sexual development in an environment of sex hormone deficiency, demonstrating the importance of both hormonal signaling and direct cell autonomous factors for somatic sex identity in birds. PMID- 26809123 TI - Is the morphology of Culicoides intersexes parasitized by mermithid nematodes a parasite adaptation? A morphometric approach to Culicoides circumscriptus (Diptera: Ceratopogonidae). AB - Mermithidae is a family of endoparasitic nematodes known to cause intersexuality in arthropods. Intersexes of the genus Culicoides parasitized by mermithids have been the object of several studies aiming to describe their particular morphology. Culicoides intersexes are specimens with male genitalia and feminized sexually dimorphic structures, i.e. antennae, mouthparts and wings. To date, these specimens have only been described qualitatively and a quantitative approach supported by statistical analysis is lacking. Here we conduct morphometric analyses of sexually dimorphic structures in a sample of Culicoides circumscriptus that includes 34 intersexes with the aim of describing precisely the intersexual morphology. The morphology of antennae and the mouthparts was studied by multivariate statistical analysis of linear measures, and wing form by implementing geometric morphometrics techniques. While intersex wings proved to have a similar size to male wings, their shape was intermediate between males and females. However, when allometric shape variation was removed, the wing shape of intersexes was almost identical to that of females. The intersex antennae were morphometrically of the female type, especially when size variation was considered. In contrast, the measured mouthparts (the labrum and the third palpal segment) were halfway between males and females, even when body size was considered. Overall, the antennae and the wings showed a higher degree of feminization than the mouthparts. These findings indicate that the degree of feminization depends both on the morphological structure and on body size. Moreover, we propose that the feminization of the wings and antennae has an adaptive meaning for the parasite, which would favor female-like traits in order to access more easily its breeding sites, where the parasite has plenty of new hosts to infect. Female-like antennae would be beneficial to detect these sites, while having female-like wings would favor the host's capacity of dispersal to these sites. PMID- 26809124 TI - A new perspective on C-reactive protein in H7N9 infections. AB - OBJECTIVES: The avian influenza H7N9 virus can cause cytokine overproduction and result in severe pneumonia and acute respiratory distress syndrome. Many studies have focused on hypercytokinemia during avian influenza infection. This study examined the association between C-reactive protein (CRP) and cytokines. METHODS: The plasma cytokine and chemokine profiles of 57 H7N9 patients were investigated using a multiplex immunoassay. The CRP levels of patients with H7N9 and patients with H1N1 were also compared. Further, the association between cytokines and CRP in H7N9 infections was explored. RESULTS: Compared with H1N1 virus, it was found that H7N9 virus induced higher expression of CRP, leading to cytokine storms. Several cytokines, including MIP-1beta, MCP-1, IP-10, and IL-6, were observed to have significantly positive relationships with CRP levels, whereas IL-17A was negatively associated with CRP levels. CONCLUSIONS: These findings suggest that CRP may be used as an early indicator to identify high-risk patients, to assess disease progression, and to determine the development of hypercytokinemia. PMID- 26809125 TI - Dengue infection as a potential trigger of an imported Plasmodium ovale malaria relapse or a long incubation period in a non-endemic malaria region. AB - OBJECTIVES: To report that dengue fever (DF) could have triggered Plasmodium ovale wallikeri malaria. METHODS: A retrospective case report of P. ovale malaria and DF in a single patient in Rio de Janeiro, Brazil, who had lived in Angola, is presented. RESULTS: On the second week of illness, the patient was referred to our research service. As symptoms had persisted up to day 14, malaria was also considered, based on the patient's long-standing epidemiological history. On day 16 of illness, a thick blood smear was positive for P. ovale (3480 parasites/mm(3)), PCR for malaria was positive for P. ovale wallikeri, and the kinetics of dengue virus (DENV) antibodies suggested a recent primary dengue infection. CONCLUSIONS: Concurrent infections of DENV and malaria have rarely been reported; the actual impact of these sequential or simultaneous infections remains unknown. Therefore, DF must be considered as a potential co-morbidity for malaria, because of its influence on fluid electrolyte management. The case presented showed consistent temporal, clinical, and laboratory evidence that the relapse or the long incubation period of P. ovale malaria may have been triggered by a recent DF episode. To the authors' knowledge, this is the first report of DENV and P. ovale co-infection. PMID- 26809126 TI - Recent advances in the use of Anti-TNFalpha therapy for the treatment of juvenile idiopathic arthritis. AB - Juvenile Idiopathic Arthritis (JIA) encompasses a group of diseases of unknown etiology having in common arthritis in at least 1 joint that persists for 6 weeks and begins before 16 years of age, with other conditions excluded. With a prevalence of 1 per 1,000 children in the USA, JIA is the most common pediatric rheumatic illness and a major cause of acquired childhood disability. During the last 20 years, the advent of host immune response modifiers known as biologic agents, in particular the anti-TNFalpha agents (etanercept, infliximab, adalimumab), which directly inhibit the action of pro-inflammatory mediators, has revolutionized the treatment and the expected outcome of JIA. This article highlights treatment indications of anti-TNFalpha drugs and their more frequent side effects in JIA patients. PMID- 26809127 TI - Pattern of Drug Resistance and Risk Factors Associated with Development of Drug Resistant Mycobacterium tuberculosis in Pakistan. AB - BACKGROUND: Drug resistant tuberculosis (DR-TB) is a major public health problem in developing countries such as Pakistan. OBJECTIVE: The current study was conducted to assess the frequency of drug resistant tuberculosis including multi drug resistance (MDR- TB) as well as risk factors for development of DR-TB, in Punjab, Pakistan. METHODOLOGY: Drug susceptibility testing (DST) was performed, using proportion method, for 2367 culture positive Mycobacterium tuberculosis (MTB) cases that were enrolled from January 2012 to December 2013 in the province of Punjab, Pakistan, against first-line anti-tuberculosis drugs. The data was analyzed using statistical software; SPSS version 18. RESULTS: Out of 2367 isolates, 273 (11.5%) were resistant to at least one anti-TB drug, while 221 (9.3%) showed MDR- TB. Risk factors for development of MDR-TB were early age (ranges between 10-25 years) and previously treated TB patients. CONCLUSION: DR TB is a considerable problem in Pakistan. Major risk factors are previous history of TB treatment and younger age group. It emphasizes the need for effective TB control Program in the country. PMID- 26809128 TI - Decreased Histone Deacetylase 2 (HDAC2) in Peripheral Blood Monocytes (PBMCs) of COPD Patients. AB - BACKGROUND: Histone deacetylase 2 (HDAC2) is a class I histone deacetylase family member that plays a critical role in suppressing inflammatory gene expression in the airways, lung parenchyma, and alveolar macrophages in patients with chronic obstructive pulmonary disease (COPD). However, the expression of HDAC2 in peripheral blood monocytes (PBMCs), nuclear factor kappa B (NF-kappaB) p65, and serum inflammatory cytokine levels in COPD patients, smokers, and non-smokers remains unclear. METHODS: PBMCs were obtained from COPD patients, healthy smokers, and healthy nonsmokers. The HDAC2 and NF-kappaB p65 expression were quantified by Western Blot. HDAC activity was assessed by an HDAC fluorometric immunoprecipitation activity assay kit. Serum tumor necrosis factor-alpha (TNF alpha) and interleukin-8 (IL-8) levels were measured by ELISA. RESULTS: HDAC2 expression and HDAC activity were decreased in PBMCs in COPD patients compared with smokers and non-smokers. Increased NF-kappaB p65 expression, serum TNF-alpha and IL-8 levels were observed in COPD patients compared with nonsmokers. The FEV1%pred was positively correlated with HDAC2 expression and HDAC activity in COPD patients. Smokers had decreased HDAC activity, increased NF-kappaB p65 expression and serum TNF-alpha compared with nonsmokers. CONCLUSIONS: HDAC2 expression was decreased in PBMCs of COPD patients and was correlated with disease severity. The reduction of HDAC2 expression not only directly enhances the expression of inflammatory genes, but may account for the activation of NF kappaB mediated inflammation. Decreased HDAC2 may serve as a potential biomarker of COPD and predict the decline of lung function. PMID- 26809129 TI - Preparation and characterization of tannase immobilized onto carboxyl functionalized superparamagnetic ferroferric oxide nanoparticles. AB - Tannase from Aspergillus tubingensis was immobilized onto carboxyl-functionalized Fe3O4 nanoparticles (CMNPs), and conditions affecting tannase immobilization were investigated. Successful binding between CMNPs and tannase was confirmed by Fourier transform infrared spectroscopy and thermogravimetric analysis. Vibrating sample magnetometry and X-ray diffraction showed that the CMNPs and immobilized tannase exhibit distinct magnetic responses and superparamagnetic properties. Free and immobilized tannase exhibited identical optimal temperatures of 50 degrees C and differing pH optima at 6 and 7, respectively. The thermal, pH, and storage stabilities of the immobilized tannase were superior to those of free tannase. After six cycles of catalytic hydrolysis of propyl gallate, the immobilized tannase maintained over 60% of its initial activity. The Michaelis constant (Km) of the immobilized enzyme indicated its higher affinity for substrate binding than the free enzyme. PMID- 26809130 TI - Analysis of the shedding of three beta-herpesviruses DNA in Polish patients subjected to allogeneic hematopoietic stem cell transplantation: Six-year follow up. AB - BACKGROUND: Infections with human beta-herpesviruses are common worldwide and are still frequent in patients after hematopoietic stem cell transplantation. Some data suggest that HHV-6 and HHV-7 could take part in CMV reactivation from latency and/or progression of CMV disease in immunosupressed patients. OBJECTIVES: The aims of this study were: (1) to summarise retrospectively the results of beta-herpesviruses DNA detection in a large group of adult allogeneic haematopoietic stem cell transplant recipients; and (2) to find a potential correlation between viruses belonging to this subfamily. STUDY DESIGN: AlloHSCT recipients (N=142) were examined in the early post-transplant period (median=89 days). The presence of CMV, HHV-6 and HHV-7 was confirmed through detection and quantification of viral DNA, isolated from 1679 sera samples. RESULTS: CMV DNA alone was detected in 23.9% of patients, while single HHV-6 and HHV-7 were detected in 14.8% and 9.9% of individuals, respectively. The reactivation of more than one virus was identified in 31% of analysed patients. In cases of concurrent infection, HHV-7 was detected at the same time as HHV-6, and both of them were usually reactivated before CMV. The kinetics of virus reactivation and measured viral load may suggest a potential role of HHV-6 and HHV-7 as co-factors in CMV reactivation. CONCLUSIONS: The observed kinetics of virus reactivation may strongly suggest a potential role of HHV-6 and/or HHV-7 as co-factors of CMV reactivation. The co-infection with these beta-herpesviruses could predispose patients after hematopoietic stem cell transplantation to a longer and more severe CMV infection. PMID- 26809131 TI - Clinical validation of AnyplexTM II HPV HR Detection according to the guidelines for HPV test requirements for cervical cancer screening. AB - BACKGROUND: AnyplexTM II HPV HR Detection (Seegene, Seoul, Korea) is a multiplex real-time PCR using tagging oligonucleotide cleavage and extension (TOCE) technology for simultaneous detection and genotyping of 14 high-risk (HR) HPV types, including HPV16 and HPV18. OBJECTIVES: To evaluate whether the clinical performance and reproducibility of AnyplexTM II HPV HR Detection meet the international consensus guidelines for HPV test requirements for cervical cancer screening [1]. STUDY DESIGN: The clinical performance of AnyplexTM II HPV HR Detection for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was determined relative to that of the reference assay, i.e., HR HPV GP5+/6+-PCR-EIA, by analysis of a total of 879 cervical liquid based cytology (LBC) specimens from a screening population, of which 60 were from women with CIN2+. The intra-laboratory reproducibility and inter-laboratory agreement were determined on 509 LBC samples, of which 172 were positive by the reference assay. RESULTS: AnyplexTM II HPV HR Detection showed a clinical sensitivity for CIN2+ of 98.3% (59/60; 95% CI: 89.1-99.8) and a clinical specificity for CIN2+ of 93.6% (764/816; 95% CI: 89.8-96.1). The clinical sensitivity and specificity were non inferior to those of HR HPV GP5+/6+-PCR-EIA (non-inferiority score test: P=0.005 and P=0.023, respectively). Both intra-laboratory reproducibility (96.8%; 95% CI: 95.3-98.1; kappa value of 0.93) and inter-laboratory agreement (96.0%; 95% CI: 94.3-97.4; kappa value of 0.91) were high. CONCLUSIONS: AnyplexTM II HPV HR Detection performs clinically non-inferior to HR HPV GP5+/6+-PCR-EIA. AnyplexTM II HPV HR Detection complies with international consensus validation metrics for HPV DNA tests for cervical cancer screening [1]. PMID- 26809132 TI - Emerging differential roles of the pRb tumor suppressor in trichodysplasia spinulosa-associated polyomavirus and Merkel cell polyomavirus pathogeneses. AB - BACKGROUND: Merkel cell carcinoma (MCC) and trichodysplasia spinulosa (TS) are two proliferative cutaneous diseases caused by the Merkel cell polyomavirus (MCPyV) and trichodysplasia spinulosa-associated polyomavirus (TSPyV) respectively. Recently, studies have elucidated a key role of the small tumor (sT) antigen in the proliferative pathogenic mechanisms of MCPyV and likely TSPyV. While both sT antigens have demonstrated a capacity in regulating cellular pathways, it remains unknown whether MCPyV and TSPyV sT antigens contribute similarly or differentially to cell proliferation. OBJECTIVES: The present study aims to explore the proliferative potential of MCPyV and TSPyV sT antigens by investigating their regulatory effects on the retinoblastoma protein (pRb) tumor suppressor. STUDY DESIGN: Inducible cell lines expressing MCPyV sT or TSPyV sT were created using a lentiviral packaging system. Cellular proteins were extracted and subjected to SDS-PAGE followed by Western blot detection and densitometric analysis. RESULTS: Expression of TSPyV sT markedly enhanced the phosphorylation of pRb in Western blot experiments. In contrast, expression of MCPyV sT did not alter pRb phosphorylation under the same experimental conditions. Densitometric analysis revealed that TSPyV sT antigen expression nearly doubled the ratio of phosphorylated to total pRb (P<0.001, Student's T test), while MCPyV sT antigen expression did not cause significant change in pRb phosphorylation status. CONCLUSION: Given that hyperphosphorylation of pRb is associated with dysregulation of the cell cycle, S-phase induction, and increased cell proliferation, our findings support an important role of TSPyV-mediated pRb deactivation in the development of TS. The observation that the pRb tumor suppressor is inactivated by TSPyV sT but not MCPyV sT provides further insights into the distinct pathobiological mechanisms of MCC and TS. PMID- 26809133 TI - Reply to the Multifaceted Aspects of Suicide Behavior by Tondo. PMID- 26809134 TI - Electron-correlation driven capture and release in double quantum dots. AB - We recently predicted that the interatomic Coulombic electron capture (ICEC) process, a long-range electron correlation driven capture process, is achievable in gated double quantum dots (DQDs). In ICEC an incoming electron is captured by one quantum dot (QD) and the excess energy is used to remove an electron from the neighboring QD. In this work we present systematic full three-dimensional electron dynamics calculations in quasi-one dimensional model potentials that allow for a detailed understanding of the connection between the DQD geometry and the reaction probability for the ICEC process. We derive an effective one dimensional approach and show that its results compare very well with those obtained using the full three-dimensional calculations. This approach substantially reduces the computation times. The investigation of the electronic structure for various DQD geometries for which the ICEC process can take place clarify the origin of its remarkably high probability in the presence of two electron resonances. PMID- 26809135 TI - Aspirin resistance in cerebrovascular disease and the role of glycoprotein IIIa polymorphism in Turkish stroke patients. AB - Aspirin resistance occurs in 5-45% of high-risk patients, with various mechanisms proposed for its development. This study aimed to determine the relationships among aspirin resistance, aspirin dosage, type of aspirin and glycoprotein IIIa P1A1/A2 polymorphism in patients with vascular risk factors. Two hundred and eight (75 symptomatic, 133 asymptomatic) patients with vascular risk factors who were using aspirin for primary or secondary prevention were prospectively included. The symptomatic group was further classified into two groups according to aspirin use at the time of stroke. Aspirin resistance was measured by the PFA 100 system (collagen/epinephrine cartridge) and glycoprotein IIIa P1A1/A2 polymorphism was determined by PCR. The overall prevalence of aspirin resistance was 32.2%. The mean age of patients with aspirin resistance was significantly higher than that in those who did not have resistance (P = 0.009). The prevalence of aspirin resistance was similar for the symptomatic and asymptomatic under aspirin therapy groups. The resistance rate was found to be highest with 100 mg enteric-coated preparation use (39.3%). Increasing the aspirin dosage and/or shifting to uncoated preparations caused a change in aspirin sensitivity of 36 60%. Repeated measurements showed development of aspirin resistance in 14% of patients who were sensitive to aspirin in previous measurements. Glycoprotein IIIaP1A1/A2 polymorphism, aspirin resistance and development of atherothrombotic stroke were not significantly related. The effect of aspirin can change by time, dosage and type of preparation used. There are no relationships among glycoprotein IIIa P1A1/A2 polymorphism, aspirin resistance and development of atherothrombotic stroke. PMID- 26809136 TI - Novel nonquaternary reactivators showing reactivation efficiency for soman inhibited human acetylcholinesterase. AB - Soman is a highly toxic nerve agent with strong inhibition of acetylcholinesterase (AChE), but of the few reactivators showing antidotal efficiency for soman-inhibited AChE presently are all permanently charged cationic oximes with poor penetration of the blood-brain barrier. To overcome this problem, uncharged reactivators have been designed and synthesized, but few of them were efficient for treating soman poisoning. Herein, we used a dual site biding strategy to develop more efficient uncharged reactivators. The ortho hydroxylbenzaldoximes were chosen as reactivation ligands of AChE to prevent the secondary poisoning of AChE, and simple aromatic groups were used as peripheral site ligands of AChE, which were linked to the oximes in a similar way as that found in the reactivator HI-6. The in vitro experiment demonstrated that some of the resulting conjugates have robust activity against soman-inhibited AChE, and oxime 8b was highlighted as the most efficient one. Although not good as HI-6 in vitro, these new compounds hold promise for development of more efficient centrally acting reactivators for soman poisoning due to their novel nonquaternary structures, which are predicted to be able to cross the blood-brain barrier. PMID- 26809137 TI - Cadmium induces NLRP3 inflammasome-dependent pyroptosis in vascular endothelial cells. AB - Cadmium (Cd) is an important and common environmental pollutant that has been linked to cardiovascular diseases, such as atherosclerosis and hypertension. Increasing evidence demonstrates that Cd impairs the cardiovascular system by targeting vascular endothelial cells, but the underlying mechanisms remain obscure. In human umbilical vein endothelial cells (HUVECs), we observed that Cd treatment led to cell death and the generation of inflammatory cytokines. The Cd induced cell death was identified as pyroptosis, a novel pro-inflammatory form of cell death depending on caspase-1 activation. In addition, exposure of HUVECs to Cd resulted in NLRP3 inflammasome activation as evidenced by cleavage of caspase 1 and downstream interleukin (IL)-1beta production. Moreover, knockdown of NLRP3 by small interfering RNA efficiently suppressed Cd-induced caspase-1 cleavage, IL 1beta production and pyroptosis in HUVECs. Additional experiments demonstrated that treatment with Cd significantly increased the levels of mitochondrial reactive oxygen species (mtROS) and intracellular ROS in HUVECs. Accordingly, pre treatment with mtROS scavenger or total ROS scavenger reduced Cd-induced activation of NLRP3 inflammasome and pyroptotic cell death. Taken together, our data suggest that NLRP3 inflammasome, activated by the generation of mtROS, mediates Cd-induced pyroptosis in HUVECs. Our results provide novel insights into Cd-induced cytotoxicity and the underlying mechanism by which Cd induces endothelial injury. PMID- 26809139 TI - Mechanisms of beauvericin toxicity and antioxidant cellular defense. AB - Beauvericin (BEA) is a secondary metabolite produced by many species of fungus Fusarium. This study determines the injury (cell viability, cell proliferation, mitochondrial membrane potential, cell death and DNA damage) and the intracellular defense mechanisms (catalase and superoxide dismutase) in Chinese Hamster ovary (CHO-K1) cells after BEA exposure. The results obtained in this study demonstrated that BEA induces cytotoxicity in a dose- and time-dependent manner in CHO-K1 cells. Moreover, disruption in mitochondrial enzymatic activity and cell proliferation has been observed after BEA exposure, which can lead or be consequence of cell death. BEA inhibits cell proliferation by arresting cells in G0/G1 and increasing apoptosis. Moreover, at higher exposure times, BEA induces differentiation of CHO-K1 cells through G2/M arrest, preventing that cells entry into mitosis. DNA strand breaks were observed at 1 MUM after 24h of exposure. On the other hand, the SOD and CAT activities were increased after BEA exposure and as a defense system they could contribute to eliminate damage produced by BEA and oxidants products generated in CHO-K1 cells. PMID- 26809138 TI - Heme oxygenase-1 alleviates cigarette smoke-induced restenosis after vascular angioplasty by attenuating inflammation in rat model. AB - Cigarette smoke is not only a profound independent risk factor of atherosclerosis, but also aggravates restenosis after vascular angioplasty. Heme oxygenase-1 (HO-1) is an endogenous antioxidant and cytoprotective enzyme. In this study, we investigated whether HO-1 upregulating by hemin, a potent HO-1 inducer, can protect against cigarette smoke-induced restenosis in rat's carotid arteries after balloon injury. Results showed that cigarette smoke exposure aggravated stenosis of the lumen, promoted infiltration of inflammatory cells, and induced expression of inflammatory cytokines and adhesion molecules after balloon-induced carotid artery injury. HO-1 upregulating by hemin treatment reduced these effects of cigarette smoke, whereas the beneficial effects were abolished in the presence of Zincprotoporphyrin IX, an HO-1 inhibitor. To conclude, hemin has potential therapeutic applications in the restenosis prevention after the smokers' vascular angioplasty. PMID- 26809140 TI - Preparation of Substrate for Flavorant from Chicken Bone Residue with Hot Pressure Process. AB - Hot-pressure extraction (HPE), which is regarded as a "green" technology, was applied to extract nutrients (protein, collagen, and minerals) from chicken bone residue (CBR). Amino acids (AA), color, and volatile flavor compounds of chicken bone extract (CBE) were also investigated. Results showed that contents of protein, total soluble solids, minerals, and collagen of CBE were positively correlated with extraction time and temperature. High ratios of protein (83.51%) and collagen (96.81%) were obtained with 135 degrees C and 120 min. Essential AA accounted for 31.03% to 47.73% of total AA in CBE. The percentage of bitter AA in TAA decreased from 28.94% to 25.02% at 0 min to 20.19% and 21.41% at 120 min, although fresh AA increased from 46.35% to 50.84% (0 min) to 53.14% (120 min) at 130 and 135 degrees C, respectively, indicating CBE was nutritionally beneficial with good flavor. Color and volatile flavor of CBE improved significantly after extraction, although calcium in CBE (4.2 to 4.8 mg/100 g) was relatively low compared with that of CBR (1078 mg/100 g). It can be concluded that HPE is a promising way to transform CBR into a nutritious flavorant substrate, but it is not an efficient way to extract calcium. PMID- 26809141 TI - Is environmental radon gas associated with the incidence of neurodegenerative conditions? A retrospective study of multiple sclerosis in radon affected areas in England and Wales. AB - To test whether an association exists between radon gas concentration in the home and increased multiple sclerosis (MS) incidence, a retrospective study was undertaken of MS incidence in known areas of raised domestic radon concentration in England and Wales, using The Health Improvement Network (THIN) clinical research database. The study population comprised 20,140,498 person-years of clinical monitoring (males: 10,056,628: 49.93%; females: 10,083,870: 50.07%), representing a mean annual population of 2.5 million individuals. To allow for the possible latency of MS initiation following exposure, data extraction was limited to patients with at least five years registration history with the same GP practice before first diagnosis. Patient records were allocated to one of nine radon concentration bands depending on the average radon level in their postcode sector. MS incidence was analysed by searching for patients with first MS diagnosis over the eight calendar years 2005-2012 inclusive. 1512 new MS cases were diagnosed, 1070 females, 442 males, equivalent to raw incidence rates of 7.51, 10.61 and 4.40 per 10(5) person-years respectively, comparable to previously reported results. Of these new cases, 115 could be allocated to one of the radon bands representing high radon areas. Standardising to the UK 2010 population, excess relative risk (ERR) figures for MS were calculated for each radon band. Linear regression of ERR against mean band radon concentration shows a positive gradient of 0.22 per 100 Bq.m(-3) (R(2) = 0.25, p = 0.0961) when forced through the origin to represent a linear-no-threshold response. The null hypothesis falls inside the 95% confidence interval for the linear fit and therefore this fit is not statistically significant. We conclude that, despite THIN sampling around 5% of the population, insufficient data was available to confirm or refute the hypothesised association between MS incidence and radon concentration. PMID- 26809142 TI - Poverty, inequality, and increased consumption of high calorie food: Experimental evidence for a causal link. AB - Rising obesity represents a serious, global problem. It is now well established that obesity is associated with poverty and wealth inequality, suggesting that these factors may promote caloric intake. Whereas previous work has examined these links from an epidemiological perspective, the current paper examined them experimentally. In Study 1 we found that people experimentally induced to view themselves as poor (v. wealthy) exhibited increased calorie intake. In Study 2, participants who believed that they were poorer or wealthier than their interaction partners exhibited higher levels of anxiety compared to those in an equal partners condition; this anxiety in turn led to increased calorie consumption for people who had a strong need to belong. The findings provide causal evidence for the poverty-intake and inequality-intake links. Further, we identify social anxiety and a strong need to belong as important social psychological factors linking inequality to increased calorie intake. PMID- 26809143 TI - Sensory evaluation of a novel vegetable in school age children. AB - A behavioural sensory task was undertaken to further understanding into whether children's sensory evaluation of a new vegetable is associated with tasting and food neophobia scores. A sample of ninety-five children, aged 7-11 years, was recruited from a primary school in inner city Birmingham, UK. They were asked to rate the sight, smell and feel of a familiar vegetable (carrot) and an unfamiliar vegetable (celeriac) in a randomised order to control for order effects. They were then asked to try the each vegetable, and rate its taste. It was found that children rated the sensory characteristics of the familiar vegetable more positively than the novel vegetable across all sensory domains (p < 0.05). Refusing to try the novel vegetable was associated with food neophobia scores and olfactory ratings. The ratings of the taste of the novel vegetable were associated with olfactory and tactile ratings. In addition there was a clear developmental shift in the sample with younger children being more likely to rate the novel vegetable as 'looking strange' and older children rating the novel vegetable as 'smelling strange'. This research strengthens the idea that sensory information is important in children deciding to try, and their hedonic evaluation of the taste of a new vegetable. PMID- 26809144 TI - The glycogen metabolism via Akt signaling is important for the secretion of enamel matrix in tooth development. AB - Cells alter their energy metabolism depending on the stage of differentiation or various environments. In the ameloblast differentiation of continuous growing mouse incisors, we found temporary glycogen storage in preameloblasts before the start of enamel matrix secretion and investigated the relationship between enamel matrix secretion and glycogen metabolism. Immunohistochemistry showed that in the transitional stage from preameloblasts to secretory ameloblasts, the glycogen synthase changed from the inactive form to the active form, the expression of glycogen phosphorylase increased, and further, the levels of IGF-1, IGF-1 receptor and activated Akt increased. These results suggested that the activation of Akt signaling via IGF is linked to the onset of both glycogen metabolism and enamel matrix deposition. In the experiments using organ culture and ameloblast cell line, the activation of Akt signaling by IGF-1 stimulated glycogen metabolism through the up-regulation of Glut-1,-4 and Gsk-3beta and the dephosphorylation of glycogen synthase. Subsequently, they resulted in increased enamel matrix secretion. In contrast, some inhibitors of Akt signals and glycogen synthesis/degradation down-regulated enamel matrix secretion. Taking these findings together, glycogen metabolism via Akt signaling is an essential system for the secretion of enamel matrix in ameloblast differentiation. PMID- 26809146 TI - Elastic constants of beryllium: a first-principles investigation. AB - We apply several recently introduced projector-augmented wave, ultrasoft, and norm-conserving pseudopotentials (PPs) to the calculation of the elastic constants of beryllium and compare the results with previous theory and experiments. We discuss how the elastic constants depend on the Brillouin zone integration, the PP type, and the exchange and correlation functional. We find that although in percentage terms the elastic constants of beryllium depend on the PPs more than the crystal parameters or the bulk moduli, the differences between the local density approximation (LDA) and the Perdew, Burke, and Ernzerhof (PBE) generalized-gradient approximation are larger than the PP differences. The LDA overestimates compared to experiments, while the PBE values are higher than those of experiments but show a much better agreement. The PBEsol functional gives values that are slightly higher than those from PBE, with differences comparable to the PP uncertainty. We propose a simple formula to rationalize the internal relaxations in hexagonal close-packed crystals and show that Be relaxations are in reasonable agreement with this formula. The effects of internal relaxations on the values of C11 and C12 amount to a few per cent of C11, but up to 50% of C12. PMID- 26809145 TI - Skin Autofluorescence Is Associated with Endothelial Dysfunction in Uremic Subjects on Hemodialysis. AB - BACKGROUND: Elevated levels of advanced glycation end products (AGEs) within tissues may contribute to endothelial dysfunction, an early indicator of atherosclerosis. We aimed to investigate whether levels of skin AGEs could be a useful marker to predict endothelial dysfunction in uremic subjects on hemodialysis. METHODS AND RESULTS: One hundred and nineteen uremic patients on hemodialysis and 57 control subjects with moderate-to-high cardiovascular risk factors and without chronic kidney disease (CKD) were enrolled. We used ultrasound to measure flow-mediated vasodilation (FMD). An AGE reader measured skin autoflurorescence (AF). We then compared differences in FMD and skin AF values between the two groups. The uremic subjects had significantly higher levels of skin AF (3.47+/-0.76 AU vs. 2.21+/-0.45 arbitrary units; P<0.01) and significantly lower levels of FMD (4.79%+/-1.88% vs. 7.19%+/-2.17%; P<0.01) than the non-CKD subjects. After adjusting for all potential covariates, we found that skin AF level independently predicted FMD in both the hemodialysis and the non CKD groups. In the hemodialysis group, skin AF >= 3.05 arbitrary units predicted abnormal FMD at a sensitivity of 87.9% and a specificity of 78.6% (P<0.01). CONCLUSIONS: Skin AF could be a useful marker to predict endothelial dysfunction in uremic subjects on hemodialysis. PMID- 26809147 TI - A rare cause of low back pain: intraspinal synovial cyst containing gas. PMID- 26809148 TI - Diagnosis and neurologic status as predictors of surgical site infection in primary cervical spinal surgery. AB - BACKGROUND CONTEXT: Surgical site infection (SSI) incidence after cervical spinal surgery ranges from 0.1% to 17%. Although the general risk factors for SSI have been discussed, the relationship of neurologic status and trauma to SSI has not been explicitly explored. PURPOSE: This study aimed to study associated risk factors and to report the incidence of SSI in patients who have undergone cervical spinal surgery with the following four preoperative diagnoses: (1) degenerative disease with no myelopathy (MP), (2) degenerative disease with MP, (3) traumatic cervical injury without spinal cord injury (SCI), (4) traumatic cervical injury with SCI. We hypothesize that SSI incidence would increase from Group (1) to Group (4). STUDY DESIGN: Retrospective database analysis was carried out. PATIENTS SAMPLE: We used International Classification of Diseases codes to identify the four groups of patients in the U.S. Nationwide Inpatient Sample (NIS) from the years 2000 to 2011. We complemented this study with a similar search in our institutional database (ID) from the years 2000 to 2013. Patients with concomitant congenital deformity, infection, inflammatory disease, and neoplasia were excluded, as were revision surgeries. OUTCOME MEASURES: The primary outcome studied was the occurrence of SSI. Statistical analyses included bivariate comparisons and chi-square distribution of demographic data and multivariable regression for demographic, surgical, and outcome variables. RESULTS: A total of 1,247,281 and 5,540 patients met inclusion criteria in the NIS database and the ID, respectively. Overall SSI incidence was 0.73% (NIS) versus 1.75% (ID). Surgical site infection incidence increased steadily from 0.52% in Group (1) to 1.97% in Group (4) in the NIS data and from 0.88% to 5.54% in the ID. Differences between diagnostic groups and cohorts reached statistical significance. Surgical site infection was predicted significantly by status (odds ratio [OR] 1.69, p<.0001) and trauma (OR 1.30, p=.0003) in the NIS data. Other significant predictors included the following: approach, number of levels fused, female gender, black race, medium size hospital, rural hospital, large hospital, western US hospital and Medicare coverage. In the ID, only trauma (OR 2.11, p=.03) reached significance when accounting for comorbidities. CONCLUSIONS: Both primary diagnosis (trauma vs. degenerative) and neurologic status (MP or SCI) were found to be strong and independent predictors of SSI in cervical spine surgery. PMID- 26809149 TI - The effectiveness of the SpineCor brace for the conservative treatment of adolescent idiopathic scoliosis. Comparison with the Boston brace. AB - BACKGROUND CONTEXT: The Boston brace (Bb) is the most widely used brace design to treat adolescent idiopathic scoliosis (AIS). The dynamic SpineCor (SC) brace is prescribed in several scoliosis clinics worldwide, but its effectiveness remains controversial. PURPOSE: The study aimed to compare the treatment effectiveness of SC in patients with AIS treated by the developers of the brace with that of the Bb at a single institution. STUDY DESIGN/SETTING: This is a retrospective comparison between a cohort of AIS patients treated using the SC brace and a cohort treated using the Bb. PATIENT SAMPLE: We assessed 243 patients treated with either Bb or SC brace to prevent the progression of AIS. OUTCOME MEASURES: The primary outcome was the progression in main Cobb angle when reaching one of the following end point criteria: (1) progression in Cobb angle of >=6 degrees , (2) main Cobb angle of >=45 degrees , (3) surgery undertaken, or (4) reaching skeletal maturity (Risser sign of 5 or growth of <1 cm in the previous 6 months). METHODS: Patients were identified at a single institution between 2000 and 2012 following the Scoliosis Research Society criteria for brace treatment: (1) diagnosis of AIS, (2) Risser sign of <=2, (3) curve magnitude between 25 degrees and 40 degrees , and (4) age >=10 years. A total of 97 patients treated with SC by the developers of the brace and 146 patients treated with Bb were identified. Data collection and radiograph measurements were performed by a single experienced nurse not involved in the decision-making for brace treatment or in the data analysis. Age and Risser sign at onset of treatment, initialmain Cobb angle, curve type, and duration of follow-up were similar in both cohorts. Statistical analysis was done using chi-square and logistic regression models, with a level of significance of .05. RESULTS: The average progression was 14.7 degrees +/-11.9 degrees in the SC cohort compared with 9.6 degrees +/-13.7 degrees in the Bb cohort (p=.003). The average Cobb angle at the end point of the study reached 47 degrees +/-13 degrees in the SC cohort and 41.7 degrees +/ 14.2 degrees in the Bb cohort (p=.005), whereas at the onset of bracing it was 32.2 degrees +/-4.9 degrees and 32.2 degrees +/-4.4 degrees , respectively, for the SC and Bb cohorts. The percentage of patients with a progression of >=6 degrees was 76% in the SC cohort and 55% in the Bb cohort (p=.001). The proportion of patients reaching 45 degrees in the SC and Bb cohorts was, respectively, 51% and 37% (p=.03), whereas the proportion of patients referred to surgery was 39% and 30%, respectively, for the SC and Bb cohorts (p=.2). The odds of progressing >=6 degrees and of reaching >=45 degrees were 2.67 and 2.07 times greater, respectively, when using the SC brace. CONCLUSIONS: The SC brace did not prevent curve progression as effectively as the Bb. Although it has the potential benefit of increasing mobility during brace wear, the SC brace was associated with increased curve progression in comparison with the Bb. There is also a trend for increased risk of requiring surgery when the SC brace is worn. PMID- 26809150 TI - Developmental trajectories of hierarchical visuo-spatial processing in fragile X syndrome and ASD: Within- and cross-syndrome variability. AB - BACKGROUND/AIMS: Despite the advances in understanding visuo-spatial processing in developmental disorders such as ASD and fragile X syndrome (FXS), less is known about the profile of those with a comorbid diagnosis, or the role of within disorder disparities between individuals across the ASD spectrum. METHODS AND PROCEDURES: Using a developmental trajectory approach, we tested 5 groups of children: Typically developing, FXS, FXS+ASD, ASD individuals who had low moderate symptoms (HFA) and ASD individuals who had severe symptoms (LFA). Symptoms of ASD were assessed using the Childhood Autism Rating Scale: CARS and hierarchical visuo-spatial processing was assessed using the Navon task. OUTCOMES AND RESULTS: Crucially, results differed between HFA and LFA participants. Furthermore, the pattern of results differed between those who had a diagnosis of FXS only and FXS+ASD. Poorer performance within the FXS groups and the group who are low functioning on the ASD spectrum indicated a delayed developmental rate compared to typical controls. CONCLUSIONS AND IMPLICATIONS: This study showed that diagnosis and severity of symptoms are indicative of differences in visuo spatial processing styles. It is important that heterogeneity within FXS and ASD populations are considered in subsequent studies and look beyond diagnostic group differences. PMID- 26809151 TI - Spatiotemporal Cluster Patterns of Hand, Foot, and Mouth Disease at the County Level in Mainland China, 2008-2012. AB - BACKGROUND: Hand, foot, and mouth disease (HFMD) is known to be a highly contagious childhood illness. In recent years, the number of reported cases of HFMD has significantly increased in mainland China. This study aims at the epidemiological features, spatiotemporal patterns of HMFD at the county/district level in mainland China. METHODS: Data on reported HFMD cases for each county from 1 January 2008 to 31 December 2012 were obtained from the Chinese Center for Disease Control and Prevention. Cluster analysis, spatial autocorrelation, and retrospective scan methods were used to explore the spatiotemporal patterns of the disease. RESULTS: The annual incidences varied greatly among the counties, ranging from 0 to 74.310/00 with the median of 5.420/00 (interquartile range: 1.540/00-13.550/00) during 2008-2012 in mainland China. Counties close to provincial capital cities generally had higher incidences than rural counties. A seasonal distribution was observed between the northern and southern China, of which dual epidemic were shown in southern China and usually only one in northern China. Based on the global and local spatial autocorrelation analysis, we found that the spatial distribution of HFMD was presented a significant clustering pattern for each year (P<0.001), and hotspots of the disease were mostly distributed in coastal provinces of China. The retrospective scan statistic further identified the dynamics of spatiotemporal clustering areas of the disease, which were mainly distributed in the counties of eastern and southern China, as well as provincial capitals and their surrounding counties. CONCLUSIONS: The spatiotemporal clustering areas of the disease identified in this way were relatively stable, and imminent public health planning and resource allocation should be focused within those areas. PMID- 26809152 TI - Fifty years of research on serotypes and mating types in Dileptus anser: A review. AB - The ciliate Dileptus anser is increasingly used as a laboratory model not only in protozoological research sensu stricto, but also in general biology. However, genetic studies of this ciliate have never been carried out, and this species is new to the comparative genetics of ciliates. This review describes the genetic experiments conducted at the Institute of Cytology of the Russian Academy of Sciences for the last 50 years. Two characters that are classical for the genetics of ciliates, serotypes and mating types were selected for analysis. The results presented do not fit into conventional genetic schemes and may have epigenetic nature. Features of this model that were revealed earlier (the simplest possible system of multiple mating types, full serial dominance of the alleles in the mat locus, the excretion of pheromones, etc.) are promising with regard to interesting comparisons of breeding systems in ciliates. The results obtained in studies of mating pheromones in D. anser have demonstrated that this model is a perspective one for further exploration of intercellular recognition in lower eukaryotes and of other related issues. PMID- 26809153 TI - The Influence of Organic Material and Temperature on the Burial Tolerance of the Blue Mussel, Mytilus edulis: Considerations for the Management of Marine Aggregate Dredging. AB - RATIONALE AND EXPERIMENTAL APPROACH: Aggregate dredging is a growing source of anthropogenic disturbance in coastal UK waters and has the potential to impact marine systems through the smothering of benthic fauna with organically loaded screening discards. This study investigates the tolerance of the blue mussel, Mytilus edulis to such episodic smothering events using a multi-factorial design, including organic matter concentration, temperature, sediment fraction size and duration of burial as important predictor variables. RESULTS AND DISCUSSION: Mussel mortality was significantly higher in organically loaded burials when compared to control sediments after just 2 days. Particularly, M. edulis specimens under burial in fine sediment with high (1%) concentrations of organic matter experienced a significantly higher mortality rate (p<0.01) than those under coarse control aggregates. Additionally, mussels exposed to the summer maximum temperature treatment (20 degrees C) exhibited significantly increased mortality (p<0.01) compared to those in the ambient treatment group (15 degrees C). Total Oxygen Uptake rates of experimental aggregates were greatest (112.7 mmol m-2 day-1) with 1% organic loadings in coarse sediment at 20 degrees C. Elevated oxygen flux rates in porous coarse sediments are likely to be a function of increased vertical migration of anaerobically liberated sulphides to the sediment-water interface. However, survival of M. edulis under bacterial mats of Beggiatoa spp. indicates the species' resilience to sulphides and so we propose that the presence of reactive organic matter within the burial medium may facilitate bacterial growth and increase mortality through pathogenic infection. This may be exacerbated under the stable interstitial conditions in fine sediment and increased bacterial metabolism under high temperatures. Furthermore, increased temperature may impose metabolic demands upon the mussel that cannot be met during burial-induced anaerobiosis. SUMMARY: Lack of consideration for the role of organic matter and temperature during sedimentation events may lead to an overestimation of the tolerance of benthic species to smothering from dredged material. PMID- 26809154 TI - How High-Need Patients Experiences the Health Care System in Nine Countries. AB - U.S. health care costs are disproportionately concentrated among older adults with multiple chronic conditions or functional limitations--a population often referred to as "high-need" patients. This analysis uses data from the Commonwealth Fund 2014 International Health Policy Survey of Older Adults to investigate health care use, quality, and experiences among high-need patients in nine countries compared with other older adults. High-need patients use a greater amount of health care services and also experience more coordination problems and financial barriers to care compared with other older adults. Disparities are particularly pronounced in the United States. The comparative success of other countries, particularly in reducing financial barriers to care, may be a product of policies that specifically target high-need patients. Similarly focusing on these populations in the U.S. and effectively managing their care may improve their health status while reducing overall costs. PMID- 26809155 TI - Language and communication development in preschool children with visual impairment: A systematic review. AB - BACKGROUND: Language and communication difficulties of young children with visual impairment (VI) are ascribed to intellectual disability, multiple disabilities and autism spectrum disorder (ASD) rather than their sensory impairment. Consequently, the communication difficulties of children with VI may have been underestimated and undertreated. OBJECTIVES: This report aims to critically appraise recent peer reviewed literature relating to communication and language development in children with VI. METHOD: A systematic search of the literature (2003-2013) was completed using the PRISMA guidelines, and primary and secondary search phrases. Nine publications were reviewed in terms of the strength of recent evidence. Thematic analysis was used to describe the early language and communication characteristics of children with VI. RESULTS: All the selected articles (n = 9) were from developed countries and participants from seven of the studies had congenital VI. Five of the studies received an evidence level rating of III while four articles were rated as IIb. Two main themes emerged from the studies: early intervention, and multiple disabilities and ASD. Language and communication development is affected by VI, especially in the early stages of development. Speech-language therapists should therefore be included in early intervention for children with VI. CONCLUSION: Recent evidence on the early language and communication difficulties of children with VI exists, but children in developing countries with acquired VI appear to not be investigated. The identified language and communication developmental characteristics may assist speech-language therapists to build a knowledge base for participation in early intervention for young children with VI and their families. PMID- 26809156 TI - Narrative review of EHDI in South Africa. AB - BACKGROUND: With 17 babies born with hearing loss every day in South Africa, there is a pressing need for systematic Early Hearing Detection and Intervention (EHDI) services. Progress is being made in offering newborn hearing screening and studies have been conducted to document these processes within South Africa. However, due to the lack of a national and holistic overview of EHDI services to date, an accurate picture of the current status of EHDI within the South African context is required. OBJECTIVE: To document and profile what has been published within the field of EHDI in South Africa over the last two decades (Jan 1995-Sept 2014) in order to gain a comprehensive overview of the current status and practice of screening and diagnosis in the field of paediatric hearing loss. METHOD: A narrative review of peer-reviewed articles related to EHDI in South Africa was conducted by searching the EBSCOHOST, SCOPUS and JSTOR databases for the period January 1995 to September 2014. RESULTS: Results indicate that over the last two decades research and publications in the field of EHDI have increased considerably. These publications have revealed extensive knowledge related to paediatric hearing screening and intervention services in South Africa; however, this knowledge seems to be limited primarily to the provinces of Gauteng and the Western Cape. Furthermore, studies pertaining to diagnosis have revealed that, although much has been written on the scientific aspects on tools for diagnosis of hearing loss, there is a lack of comprehensive information on diagnostic protocols and procedures. CONCLUSION: Despite the clear progress being made in South Africa in the field of early hearing detection and intervention, there is a need for comprehensive studies on protocols and procedures in diagnosing paediatric hearing loss. Finally, the narrative review revealed a clear need to ensure that development and growth in the field of EHDI is a national priority and extends beyond the two provinces currently showing growth. PMID- 26809157 TI - Suck, swallow and breathing coordination in infants with infantile colic. AB - BACKGROUND: There appears to be a perception amongst parents and in popular literature that infantile colic is caused by feeding difficulties. Limited support for this perception is found in scientific literature. Whilst there is scientific evidence that suck, swallow and breathing are key components of successful feeding, these components and the coordination thereof in infants with colic have not been extensively researched. OBJECTIVE: The objective of the study was to explore the suck, swallow and breathing coordination in infants with infantile colic and compare it with infants without the condition. METHOD: An assessment protocol for suck, swallow and breathing coordination was compiled from literature. This protocol was performed on a research group of 50 infants, independently diagnosed with infantile colic, and a control group of 28 infants without the condition. All participants were from two rural towns in the North West province, South Africa, selected with a snowball selection method and strict selection criteria. The study followed a static comparison group design. RESULTS: A significant difference in the key components of feeding and the presence of colic in participants of four age categories were found. The correlation between postural control and the presence of infantile colic were sustained in participants from 2-19 weeks old. CONCLUSION: Suck, swallow and breathing were found to be significantly associated with infantile colic. The findings should be investigated further. It appears that speech-language therapists may play an expanding role in infantile colic. PMID- 26809159 TI - Consuming Identities: Law, School Lunches, and What it Means to be American. AB - Food, eating, and the rituals surrounding food impact people as individuals, as groups, and as citizens. Through direct regulation, food aid, subsidies, and property rights, law shapes and even determines food choices in America. With it, law shapes, reflects, and may even--at times--dictate American identities. Perhaps nowhere is the law's impact on food and identity more immediately apparent than in the context of the National School Lunch Program (NSLP). Federally subsidized school meals feed over fifty million students a day and serve over seven billion school meals annually. Whether it is pork's removal from snack lists being likened to "fatwa" or cafeterias segregating paying and non paying students, the lessons of school meals go far beyond nutritional content and send resounding messages about civic values, inclusion, and exclusion. In recent years school meals have come under increasing scrutiny, but as legislative consideration of nutritional goals in the school lunch program has improved, discussion of political, social, and cultural goals has lagged. This Article is the first to examine the social and political dimensions of school meals, and concludes that current treatment of these values in food regulation undermines key values in American civil society. The school lunch program teaches students a simplified, uniform, and even discriminatory account of what it means to eat and be American. Students under this regime must choose to either be American and sit down at the table with the "normal" kids or retain your beliefs, your identity, and perhaps even your health and well-being. This is a choice no child should have to make--especially not on an empty stomach. PMID- 26809158 TI - Audiology practice management in South Africa: What audiologists know and what they should know. AB - BACKGROUND: In future, the South African Department of Health aims to purchase services from accredited private service providers. Successful private audiology practices can assist to address issues of access, equity and quality of health services. It is not sufficient to be an excellent clinician, since audiology practices are businesses that must also be managed effectively. OBJECTIVE: The objective was to determine the existing and required levels of practice management knowledge as perceived by South African audiologists. METHOD: An electronic descriptive survey was used to investigate audiology practice management amongst South African audiologists. A total of 147 respondents completed the survey. Results were analysed by calculating descriptive statistics. The Z-proportional test was used to identify significant differences between existing and required levels of practice management knowledge. RESULTS: Significant differences were found between existing and required levels of knowledge regarding all eight practice management tasks, particularly legal and ethical issues and marketing and accounting. There were small differences in the knowledge required for practice management tasks amongst respondents working in public and private settings. CONCLUSION: Irrespective of their work context, respondents showed that they need significant expansion of practice management knowledge in order to be successful, to compete effectively and to make sense of a complex marketplace. PMID- 26809160 TI - Eliminating the Competency Presumption in Juvenile Delinquency Cases. AB - The legal presumption used in virtually all juvenile delinquency cases in the U.S. is that all juveniles are competent to stand trial. This Article calls for the elimination of that legal presumption, which is historically based on the Dusky v. United States decision and in the adult criminal justice system. The recent decisions of the U.S. Supreme Court recognize the developmental and organic brain differences between adults and juveniles. Current research demonstrates a higher frequency rate of incompetence based on intellectual deficiencies among children when compared with adults found to be not legally competent to stand trial. By eliminating the competency presumption for juveniles in both delinquency and adult criminal proceedings, the party seeking an adjudication would be responsible for establishing that the accused juvenile is in fact, competent to stand trial. Foreign jurisdictions in Europe, Asia, Africa, and South America have long required higher thresholds--at least fourteen years of age--for holding juveniles accountable for criminal misconduct, none of them presuming that juveniles are competent to go to trial. In the alternative, by expanding the factors currently in use for determination of juvenile competency by adding developmental immaturity and mental illness, juvenile justice systems could identify the reduction of recidivist offending as the primary systemic objective. PMID- 26809161 TI - The Origination Clause, the Affordable Care Act, and Indirect Constitutional Violations. AB - "All bills for raising revenue shall originate in the House of Representatives; but the Senate may propose or concur with amendments as on other Bills." U.S. Const. art. I, S 7, cl. 1 (Origination Clause). "As we have often noted, '[c]onstitutional rights would be of little value if they could be . . . indirectly denied.'" United States Term Limits, Inc. v. Thornton, 514 U.S. 779, 829 (1995) The Supreme Court's opinion in National Federation of Independent Business v. Sebelius, upholding the constitutionality of the Patient Protection and Affordable Care Act (ACA) as a permissible exercise of Congress's taxing power rekindled an old question about the constitutionality of the Act: Was the Act unconstitutional under the Origination Clause? The bill that became the ACA, H.R. 3590, originated in the House as the Service Members Home Ownership Tax Act of 2009. It was gutted by the Senate and replaced with the ACA before being passed and sent back to the House for final passage. The Supreme Court has heard very few cases on the Origination Clause, and Origination Clause challenges have met with little success. Most of these cases have developed over the questions of whether the bill is actually a revenue-raising bill that is constitutionally required to be originate in the House, and, if so, whether the Senate amendments were appropriate. But United States Term Limits v. Thornton provides another angle under which to examine the constitutionality of the ACA: an indirect violation of a constitutional prohibition. In this Article, I will provide an overview of the ACA's passage and analyze it through the lenses of traditional Origination Clause arguments and the Term Limits approach. PMID- 26809162 TI - Testing Solutions for Adult Film Performers. AB - The majority of the nation's adult films are produced in California, and within California, most production occurs in Los Angeles. In order to regulate that content, the County of Los Angeles passed the Safer Sex in the Adult Film Industry Act (Measure B) by way of referendum in November 2012. Measure B requires that adult film producers wishing to film in Los Angeles County obtain permits from the Los Angeles County Department of Public Health, and it also mandates that adult film performers use condoms while filming and "engaging in anal or vaginal sexual intercourse." Nevertheless, between August 2013 and January 2014, several adult film performers in California tested positive for HIV, and the threat of infection remains. Although Measure B is not the best way forward for Los Angeles County, elements of the ordinance should be incorporated into future legislative efforts. Given the economic ramifications of industry flight due to more localized regulations, this Note concludes that California should pass statewide comprehensive reform. Any such new legislation must treat "independent contractors," the classification generally used for adult film performs, as if they were regular employees. Legislation should also couple mandatory testing mechanisms with provisions granting performers the right to choose whether they use condoms. Finally, legislation must include mechanisms that ensure performers' preferences are not improperly tainted by outside forces and pressures. While there will always be risks associated with the production of adult content, if undertaken, these reforms could significantly mitigate those hazards. PMID- 26809169 TI - Oxidative stress-induced Gadd45alpha inhibits trophoblast invasion and increases sFlt1/sEng secretions via p38 MAPK involving in the pathology of pre-eclampsia. AB - BACKGROUND: Pre-eclampsia (PE) is one of the most common pregnancy-related complications. We have previously reported that growth arrest and DNA damage inducible 45 alpha (Gadd45alpha) is over-expressed in trophoblasts in pre eclamptic placentas, with an excessive activation of p38 mitogen-activated protein kinase (MAPK) and increased levels of soluble Fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) in maternal sera. Now we further investigate how Gadd45alpha regulates trophoblast functions and anti-angiogenesis factors secretions during placental development in patients with PE. METHODS: Human placental villous explants were used to verify the effects of Gadd45alpha and p38 MAPK in placentation. Then HRT8/SVneo cells exposed to hypoxia/reoxygenation (H/R) were employed as an oxidative stress model to investigate the effects of Gadd45alpha on invasion and sFlt-1/sEng secretions. Through silencing Gadd45alpha with lentiviral vector-based short-hairpin RNA and inhibiting p38 MAPK with SB203580, we demonstrated that Gadd45alpha and its downstream p38 protein played roles in the pathology of pre-eclampsia. RESULTS: Gadd45alpha was found to have increased expression in H/R-treated villous explants and HTR8/SVneo cells. Gadd45alpha knockdown or p38 blockage could promote trophoblast outgrowth and migration in H/R-exposed villous explants, and enhance the potentials of trophoblast migration/invasion and network formation in H/R-exposed HTR8/SVneo cells. These functional changes might be related to the increased activities of MMP2/9. Meanwhile, Gadd45alpha knockdown or p38 inhibition also decreases sFlt 1/sEng secretions via suppressing oxidative stress. CONCLUSIONS: Oxidative stress induced overexpression of Gadd45alpha might influence the activity of MMPs through activation of p38 MAPK signaling to affect the invasion of trophoblast cells, and increase the secretions of sFlt-1/sEng, which then participate in the pathogenesis of pre-eclampsia. PMID- 26809171 TI - Social capital, substance use disorder and depression among youths. AB - BACKGROUND: Social capital - the network of social connections that exists among people - is known to be related to depression and substance use among adults. However, little is known about these relationships among adolescents, even though this age group is vulnerable due to factors of peer pressure, family, neighborhood, and maturational changes. OBJECTIVES: To evaluate the associations among social capital, substance use disorder and depression on a sample of 17 705 respondents between the ages of 12 and 17 in the 2009 National Survey of Drug Use and Health. METHODS: Structural equation modeling was used to examine social capital; responses to 48 items differentiated into two factors that measured structural social and cognitive social capital. Adolescent depression and substance use disorder were measured as past-year major depressive episodes and substance use disorder according to DSM-IV criteria. RESULTS: Structural social capital was associated with substance use disorder (beta = -0.12; p = 0.001) and depression (beta = -0.19; p = 0.001). Cognitive social capital was associated with substance use disorder (beta = -0.17; p = 0.001), but not with depression (beta = -0.002; p > 0.005). Substance use disorder mediated the association between structural and cognitive social capital and depression (beta = 0.06; p = 0.001). CONCLUSION: There was support for associations among youth structural and cognitive social capital, substance use disorder and depression. These findings suggest that additional research of a longitudinal nature is needed to determine causal connections among social capital, depression and substance use disorder for adolescents. PMID- 26809174 TI - Successful treatment of arrhythmia-induced cardiomyopathy in an infant with tuberous sclerosis complex. AB - BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal-dominant tumor suppressor gene syndrome that is characterized by the development of distinctive benign tumors and malformations in multiple organ systems (N Eng J Med 355:1345 1356, 2006). Cardiac rhabdomyomas are intracavitary or intramural tumors observed in 50-70 % of infants with TSC but only cause serious clinical problems in a very small fraction of these patients (N Eng J Med 355:1345-1356, 2006; Pediatrics 118:1146-1151, 2006; Eur J Pediatr 153:155-7, 1994); most individuals have no clinical symptoms and their tumors spontaneously regress. However, despite being clinically silent, these lesions can provoke arrhythmias and heart failure (Pediatrics 118:1146-1151, 2006; Eur J Pediatr 153:155-7, 1994). CASE PRESENTATION: We here report the clinical findings of an infant suffering from TSC complicated with dilated cardiomyopathy (DCM) after the regression of cardiac rhabdomyomas. Although his tumors improved spontaneously, tachycardia and irregular heart rate due to frequent premature ventricular and supraventricular contractions persisted from the newborn period and were refractory to several medications. His cardiomyopathy was suspected to have been induced by the tachycardia or arrhythmia. We found carvedilol therapy to be safe and highly effective in treating the cardiomyopathy. To our knowledge, this is the first case report of TSC with DCM after regression of cardiac tumors and its successful treatment. CONCLUSION: The patient's clinical course suggests that careful life long disease management is important, even in TSC patients without apparent symptoms. PMID- 26809181 TI - Morphology-Controllable Synthesis of Cobalt Telluride Branched Nanostructures on Carbon Fiber Paper as Electrocatalysts for Hydrogen Evolution Reaction. AB - Cobalt telluride branched nanostructures on carbon fiber paper (CFP) with two different morphologies were synthesized via solution-based conversion reaction. Both the CoTe2 with nanodendrite and CoTe with nanosheet morphologies on the CoTe2 nanotube (CoTe2 NDs/CoTe2 NTs and CoTe NSs/CoTe2 NTs) supported by CFP exhibit high activities toward hydrogen evolution reaction (HER). Particularly, the CoTe NSs/CoTe2 NTs only require an overpotential of 230.0 mV to deliver the current density of 100 mA cm(-2) in acid solution. After cycling for 5000 cycles or 20 h continual electrolysis, only a small performance loss is observed. PMID- 26809175 TI - Hypertension among adults in Bangladesh: evidence from a national cross-sectional survey. AB - BACKGROUND: Hypertension is an increasing problem in Southeast Asia, particularly in Bangladesh. Although some epidemiological studies on hypertension have been conducted in Bangladesh, the factors associated with hypertension in this nation remain unclear. We aimed to determine the factors associated with hypertension among the adults in Bangladesh. METHODS: We conducted a cross-sectional study using data from the nationally representative 2011 Bangladesh Demographic and Health Survey (BDHS). A total of 7,839 (3,964 women and 3,875 men) adults aged 35 years and older who participated in the survey was included. Hypertension was defined by a systolic blood pressure >= 140 mmHg and/or, diastolic blood pressure >= 90 mmHg and/or, receipt of an anti-hypertensive medication at time of the survey. The degree of association between the risk factors and the outcome was assessed by the odd ratio (OR) obtained from the bivariate and multivariable logistic regression models. RESULTS: The overall prevalence of hypertension was 26.4 %, and the prevalence was higher in women (32.4%) than men (20.3%). Study participants with the age group of 60-69 years had higher odds of having hypertension (AOR: 3.77, 95% CI: 3.01-4.72) than the age group 35-39 years. Moreover, individuals who had higher educational attainment (AOR: 1.63, 95% C.I: 1.25-2.14) and higher wealth status (AOR = 1.91, 95% CI: 1.54-2.38) had higher odds of having hypertension than the individuals with no education and lower social status, respectively. The analysis also showed that high BMI (AOR: 2.19, 95% C.I: 1.87-2.57) and having diabetes (AOR: 1.54, 95% C.I: 1.31-1.83) were associated with the increasing risk of hypertension. CONCLUSIONS: Our study shows that the risk of hypertension was significantly associated with older age, sex, education, place of residence, working status, wealth index, BMI, and diabetes. Moreover, hypertension is largely untreated, especially in rural settings. The health system needs to develop appropriate strategies including early diagnosis, awareness via mass media, and health education programs for changing lifestyles should be initiated for older age, wealthy, and/or higher educated individuals in Bangladesh. Moreover, area-specific longitudinal research is necessary to find out the underlying causes of regional variations. PMID- 26809184 TI - Meta-connectomics: human brain network and connectivity meta-analyses. AB - Abnormal brain connectivity or network dysfunction has been suggested as a paradigm to understand several psychiatric disorders. We here review the use of novel meta-analytic approaches in neuroscience that go beyond a summary description of existing results by applying network analysis methods to previously published studies and/or publicly accessible databases. We define this strategy of combining connectivity with other brain characteristics as 'meta connectomics'. For example, we show how network analysis of task-based neuroimaging studies has been used to infer functional co-activation from primary data on regional activations. This approach has been able to relate cognition to functional network topology, demonstrating that the brain is composed of cognitively specialized functional subnetworks or modules, linked by a rich club of cognitively generalized regions that mediate many inter-modular connections. Another major application of meta-connectomics has been efforts to link meta analytic maps of disorder-related abnormalities or MRI 'lesions' to the complex topology of the normative connectome. This work has highlighted the general importance of network hubs as hotspots for concentration of cortical grey-matter deficits in schizophrenia, Alzheimer's disease and other disorders. Finally, we show how by incorporating cellular and transcriptional data on individual nodes with network models of the connectome, studies have begun to elucidate the microscopic mechanisms underpinning the macroscopic organization of whole-brain networks. We argue that meta-connectomics is an exciting field, providing robust and integrative insights into brain organization that will likely play an important future role in consolidating network models of psychiatric disorders. PMID- 26809187 TI - Butanol tolerance of carboxydotrophic bacteria isolated from manure composts. AB - Carboxydotrophic bacteria (carboxydotrophs) have the ability to uptake carbon monoxide (CO) and synthesize butanol. The aims of this study were to determine the butanol tolerance and biological production of butanol carboxydotrophic strains. In this study, 11 carboxydotrophic strains were exposed to increasing n butanol concentrations (1-3% vol/vol) to determine their effect on growth. Butanol production by the strains was quantified and the identity of the strains was elucidated using 16S rRNA sequencing. The carboxydotrophic strains possessed inherent tolerance to butanol and tolerated up to 3% n-butanol. Among the 11 strains, T1-16, M2-32 and M3-28 were the most tolerant to butanol. The 16S rRNA gene sequence of these strains was similar (99% nucleotide similarity) to the butanol-tolerant strains Bacillus licheniformis YP1A, Pediococcus acidilacti IMUA20068 and Enterococcus faecium IMAU60169, respectively. The carboxydotrophic strains screened in this study have two distinct features: (1) high tolerance to butanol and (2) natural production of low concentration of butanol from CO, which distinguish them from other screened butanol-tolerant strains. The butanol tolerance of these carboxydotrophic strains makes them ideal for genetic studies, particularly the molecular mechanisms that enable them to survive such hostile environmental conditions and the identification of genes that confer tolerance to butanol. PMID- 26809188 TI - Pharmacokinetics of drugs in adult living donor liver transplant patients: regulatory factors and observations based on studies in animals and humans. AB - INTRODUCTION: Limited information is available on the pharmacokinetics of drugs in the donors and recipients following adult living donor liver transplantation (LDLT). Given that both the donors and recipients receive multiple drug therapies, it is important to assess the pharmacokinetics of drugs used in these patients. AREAS COVERED: Pathophysiological changes that occur post-surgery and regulatory factors that may influence pharmacokinetics of drugs, especially hepatic drug metabolism and transport in both LDLT donors and the recipients are discussed. Pharmacokinetic data in animals with partial hepatectomy are presented. Clinical pharmacokinetic data of certain drugs in LDLT recipients are further reviewed. EXPERT OPINION: It takes up to six months for the liver volume to return to normal after LDLT surgery. In the LDLT recipients, drug exposure generally is higher with lower clearance during early period post-transplant; lower initial dosages of immunosuppressants are used than deceased donor liver transplant recipients during the first six months post-transplantation. In animals, the activities of hepatic drug metabolizing enzymes and transporters are known to be altered differentially during liver regeneration. Future studies on the actual hepatic function with reference to drug metabolism, drug transport, and biliary secretion in both LDLT donors and recipients are required. PMID- 26809189 TI - Erratum to: Assessment of the quality of fall detection and management in primary care in the Netherlands based on the ACOVE quality indicators. PMID- 26809190 TI - The vitamin D status in ankylosing spondylitis in relation to intestinal inflammation, disease activity, and bone health: a cross-sectional study. AB - We assessed the vitamin D status in ankylosing spondylitis (AS) patients and healthy controls in the late winter when no vitamin D is produced by the sunlight. The vitamin D status was often poor, but not lower in AS and not associated with disease activity or signs of gut inflammation. INTRODUCTION: The aims of the study were to investigate the vitamin D levels attained mainly by dietary intake in ankylosing spondylitis (AS) in comparison with healthy controls and in relation to gut inflammation, measured indirectly by fecal calprotectin, disease activity, osteoproliferation, bone mineral density (BMD), and vertebral fractures. METHODS: Serum 25-hydroxy vitamin D (25(OH)D) was measured in 203 AS patients and 120 healthy controls at the end of "the vitamin D winter," when the out-door UVB irradiation is too low to allow synthesis of vitamin D3 in the skin at the latitude of Gothenburg, Sweden. Fecal calprotectin was measured in stool samples. Disease activity was assessed with CRP, ESR, ASDASCRP, BASDAI, BAS-G, BASFI, and BASMI. Lateral spine radiographs were scored for osteoproliferation and vertebral fractures using the mSASSS and Genant scores. BMD was measured in the lumbar spine and femoral neck. RESULTS: Vitamin D insufficiency (a serum 25(OH)D <50 nmol/L) was found in approximately 50 % of the AS patients, but serum 25(OH)D was not different from healthy controls and not significantly correlated with fecal calprotectin, gastrointestinal symptoms, disease activity parameters, mSASSS, BMD, or vertebral fractures. CONCLUSIONS: The vitamin D status was often poor in the late winter in AS but not different from the healthy controls. No evidence for a connection between subclinical gut inflammation, malabsorption, and hypovitaminosis D was found. Serum 25(OH)D was not associated with disease activity, osteoproliferation, BMD, or vertebral fractures. We suggest that the lower vitamin D levels in AS, previously found by others, may be caused by reduced out-door UVB exposure. PMID- 26809191 TI - The effects of body mass index on the hereditary influences that determine peak bone mass in mother-daughter pairs (KNHANES V). AB - A daughter's bone mineral density (BMD) is significantly correlated with her mother's BMD, but the daughter's body mass index (BMI) could modulate this association. Maternal inheritance dominantly affects daughters with a lower BMI, but BMI could compensate for hereditary influences in daughters with a higher BMI in terms of daughter's BMD. INTRODUCTION: Achieving optimal peak bone mass at a young age is the best way to protect against future osteoporosis and subsequent fractures. Although environmental components influence bone mass accrual, but peak bone mass is largely programmed by inheritance. The aims of this study were to investigate the influence of maternal inheritance on the daughter's bone mass and to assess whether these influences differ according to the daughter's body mass index (BMI). METHODS: We used data obtained from the 2010 Korean National Health and Nutrition Examination Survey V and included 187 mother-daughter pairs. Bone mineral density (BMD) was measured at the lumbar spine (LS), femur neck (FN), and total hip (TH) by using dual-energy X-ray absorptiometry (DXA). The daughter group was stratified into two groups according to the mean BMI (21.4 kg/m(2)). RESULTS: The daughters' BMD correlated significantly with both their BMI and their mothers' Z-score for each skeletal site. In the daughters with a lower BMI (<=21.4 kg/m(2)), the BMDs at the FN and TH were affected more by the mothers' Z-score than by the daughters' BMI. Meanwhile, the influence of the daughters' BMI on their BMD was higher than that of their mothers' Z-score in daughters with a higher BMI (>21.4 kg/m(2)). Moreover, the mothers' Z-scores were a significant predictor of their daughters having Z-scores < -1.0 only in daughters with a lower BMI. CONCLUSIONS: This study suggests that maternal inheritance is an important determinant of the daughters' bone mass, but that this hereditary factor may vary according to the daughters' BMI. PMID- 26809192 TI - Xanthotoxin prevents bone loss in ovariectomized mice through the inhibition of RANKL-induced osteoclastogenesis. AB - Xanthotoxin (XAT) is extracted from the seeds of Ammi majus. Here, we reported that XAT has an inhibitory effect on osteoclastogenesis in vitro through the suppression of both receptor activator of nuclear factor-kappaB ligand (RANKL) induced ROS generation and Ca(2+) oscillations. In vivo studies showed that XAT treatment decreases the osteoclast number, prevents bone loss, and restores bone strength in ovariectomized mice. INTRODUCTION: Excessive osteoclast formation and the resultant increase in bone resorption activity are key pathogenic factors of osteoporosis. In the present study, we have investigated the effects of XAT, a natural furanocoumarin, on the RANKL-mediated osteoclastogenesis in vitro and on ovariectomy-mediated bone loss in vivo. METHODS: Cytotoxicity of XAT was evaluated using bone marrow macrophages (BMMs). Osteoclast differentiation, formation, and fusion were assessed using the tartrate-resistant acid phosphatase (TRAP) stain, the actin cytoskeleton and focal adhesion (FAK) stain, and the fusion assay, respectively. Osteoclastic bone resorption was evaluated using the pit formation assay. Reactive oxygen species (ROS) generation and removal were evaluated using dichlorodihydrofluorescein diacetate (DCFH-DA). Ca(2+) oscillations and their downstream signaling targets were then detected. The ovariectomized (OVX) mouse model was adopted for our in vivo studies. RESULTS: In vitro assays revealed that XAT inhibited the differentiation, formation, fusion, and bone resorption activity of osteoclasts. The inhibitory effect of XAT on osteoclastogenesis was associated with decreased intracellular ROS generation. XAT treatment also suppressed RANKL-induced Ca(2+) oscillations and the activation of the resultant downstream calcium-CaMKK/PYK2 signaling. Through these two mechanisms, XAT downregulated the key osteoclastogenic factors nuclear factor of activated T cells c1 (NFATc1) and c-FOS. Our in vivo studies showed that XAT treatment decreases the osteoclast number, prevents bone loss, rescues bone microarchitecture, and restores bone strength in OVX mice. CONCLUSION: Our findings indicate that XAT is protective against ovariectomy-mediated bone loss through the inhibition of RANKL-mediated osteoclastogenesis. Therefore, XAT may be considered to be a new therapeutic candidate for treating osteoporosis. PMID- 26809193 TI - Psychiatric Distress, Drug Use, and HIV Viral Load Suppression in Russia. AB - To explore the influence of psychiatric distress and substance use on viral load suppression in HIV-infected patients taking ART we analyzed socio-demographic characteristics, CD4+ cells count and viral loads, the Symptom Check List-90 and the Addiction Severity Index of 75 patients who had taken ART for at least 6 month. Using viral load data as the marker of ART success, we divided the sample into two groups. Comparison of the groups showed that education, marriage, and female gender are predictors of optimal viral load suppression. Overall results failed to demonstrate substance use and psychiatric distress as predictors of viral load suppression. PMID- 26809194 TI - Fluoroalkylsilane-Modified Textile-Based Personal Energy Management Device for Multifunctional Wearable Applications. AB - The rapid development of wearable electronics in recent years has brought increasing energy consumption, making it an urgent need to focus on personal energy harvesting, storage and management. Herein, a textile-based personal energy management device with multilayer-coating structure was fabricated by encapsulating commercial nylon cloth coated with silver nanowires into polydimethylsiloxane using continuous and facile dip-coating method. This multilayer-coating structure can not only harvest mechanical energy from human body motion to power wearable electronics but also save energy by keeping people warm without losing heat to surroundings and wasting energy to heat empty space and inanimate objects. Fluoroalkylsilanes (FAS) were grafted onto the surface of the film through one single dip-coating process to improve its energy harvesting performance, which has hardly adverse effect to heat insulation and Joule heating property. In the presence of FAS modification, the prepared film harvested mechanical energy to reach a maximum output power density of 2.8 W/m(2), charged commercial capacitors and lighted LEDs, showing its potential in powering wearable electronics. Furthermore, the film provided 8% more thermal insulation than normal cloth at 37 degrees C and efficiently heated to 40 degrees C within 4 min when applied the voltage of only 1.5 V due to Joule heating effect. The high flexibility and stability of the film ensures its wide and promising application in the wearable field. PMID- 26809197 TI - Enhancement of electrochemical properties by polysulfide trapping in a graphene coated sulfur cathode on patterned current collector. AB - A sulfur cathode on a honeycomb-shape-patterned Al current collector was prepared and successfully sealed using triple-layered graphene. Graphene layers on the sulfur cathode well confined the dissolved polysulfide in the electrode, leading to significantly enhanced electrochemical properties including cycle retention and Coulombic efficiency. PMID- 26809200 TI - [Leg ulcers: Should general practitioners hospitalize their patients?]. AB - OBJECTIVES: Determine whether general practitioners have sufficient expertise in the field of leg ulcers. METHOD: A cross-sectional survey was conducted among 179 general practitioners working in the region Ile-de-France to evaluate the implementation of leg ulcer guidelines issued by the Superior Health Authority (HAS) in 2006. Participating physicians were either internship supervisors or practitioners in Paris' 14th district. RESULTS: The first hundred usable answers (response rate 65%) came from 71 internship supervisors and 29 practitioners of Paris' 14th district. Only 40% of the physicians were aware of the guidelines, with no significant difference noted between the two groups. 9/10 practitioners examined less than 10 patients with leg ulcers per year. Physical examinations were done according to the guidelines and a venous Doppler was prescribed in two thirds of the cases. The ankle-brachial pressure index (ABPI) essential to diagnose lower limb arteriopathy was measured for only 10% of the patients. In accordance with the guidelines, compression was by far (73%) considered as the main treatment as compared to dressing (37%), but compression therapy was well prescribed in only one-third of the cases. Despite poor prognosis criteria (characteristic and time course), referral for a specialized opinion was rare. CONCLUSION: Even if they were not always aware of the detailed guidelines, the practitioners applied the main recommendations. Nevertheless, practices could be improved by measuring the ABPI, searching for a diagnosis of arteriopathy, and better prescription of compression therapy. General practitioners should refer patients with leg ulcers to a specialized hospital unit. PMID- 26809201 TI - Two Ways of Knowing: Big Data and Evidence-Based Medicine. PMID- 26809202 TI - Single-port laparoscopic surgery for benign salpingo-ovarian pathology: a single center experience from Saudi Arabia. AB - BACKGROUND: There are limited data and few solid conclusions on the use of single port laparoscopic surgery (SPLS) in gynecologic procedures. OBJECTIVE: The objective of our descriptive study was to review our single-center experience with benign salpingo-ovarian conditions (feasibility, safety and surgical outcomes). DESIGN: A retrospective cross-sectional study from January-2012 to October-2014. SETTING: King Faisal Specialist Hospital & Research Center--a referral tertiary healthcare center. PATIENTS AND METHODS: All gynecologic patients who underwent SPLS procedures for benign adnexal pathologies were analyzed for pre-, intra-and postoperative details. SPLS was done using a single multi-port trocar and standard laparoscopic instruments. MAIN OUTCOME MEASURES: Perioperative complications and conversion rate. RESULTS: Eighty (n=80) patients underwent SPLS interventions. the median age and BMi were 37 years and 24.6 kg/m2, respectively. Thirty-one patients (38.8%) had >=1 previous abdominopelvic surgeries. Of 104 SPLS procedures conducted, the three most common procedures were unilateral ovarian cystectomy (n=21/104; 20.2%), bilateral ovarian transposition (n=20/104; 19.2%), and unilateral salpingo-oophorectomy (n=16/104; 15.4%). No patient required addition of extra ports or conversion to conventional multi-port laparoscopy or laparotomy. The median operative time, estimated blood loss and hospital stay were 66 min, 10 mL and 1 day, respectively. No patient experienced major intraoperative or postoperative complications. the median postoperative pain grade using the visual analogue scale was 2 (examined in 74 of 80 patients). At six-weeks postoperatively, the median wound scar length (measured at outpatient clinic) was 1.2 cm. CONCLUSION: SPLS in the management of benign salpingo-ovarian conditions is generally feasible, potentially safe, and associated with satisfactory operative and postoperative outcomes. LIMITATIONS: Retrospective and non-comparative design. Single-center experience. Subjective scores of the patients' self-reported satisfaction about post-operative pain, subject to recall bias. PMID- 26809203 TI - Ultrasound and magnetic resonance imaging assessment of joint disease in symptomatic patients with cystic fibrosis arthropathy. AB - OBJECTIVES: Cystic fibrosis arthropathy (CFA) is a term commonly used for joint pain with and without swelling seen in some patients with CF. Early studies into CFA focused on the presence of rheumatoid factor and immunological changes on synovial biopsy, with parallels drawn between respiratory and joint activity. Identification of anti-cyclic citrullinated peptide antibodies (anti-CCP) as a marker of rheumatoid arthritis (RA), along with increased access to sensitive imaging techniques including ultrasound (US) and magnetic resonance imaging (MRI), offer great potential to investigate and more accurately understand the type(s) of inflammatory arthritis that may underlie CFA. The aim of this study was to phenotype an active CFA cohort using serology and imaging, as a basis for further work in this understudied area. METHODS: This was a prospective observational cohort study of symptomatic CFA patients presenting with joint pain. Participants underwent serological testing, clinical and US joint and entheseal assessment, as well as MRI of the most symptomatic joint/joint area. RESULTS: Ten symptomatic patients were studied with 9/10 having positive clinical findings. Inflammatory changes on US were seen in 8/10 cases. Five patients had positive findings on MRI (3 of whom had received IV gadolinium contrast). This included patients with significant erosive changes. One patient was anti-CCP positive suggestive of RA, and two were anti-nuclear antibody positive. CONCLUSION: Imaging, and to a lesser extent serology, identified inflammatory joint pathology in a proportion of cases, providing important data to explore in a large CFA cohort examining the clinical and imaging phenotype of this group. PMID- 26809205 TI - Site-directed immobilization of a genetically engineered anti-methotrexate antibody via an enzymatically introduced biotin label significantly increases the binding capacity of immunoaffinity columns. AB - In this study, the effect of random vs. site-directed immobilization techniques on the performance of antibody-based HPLC columns was investigated using a single domain camelid antibody (VHH) directed against methotrexate (MTX) as a model system. First, the high flow-through support material POROS-OH was activated with disuccinimidyl carbonate (DSC), and the VHH was bound in a random manner via amines located on the protein's surface. The resulting column was characterized by Frontal Affinity Chromatography (FAC). Then, two site-directed techniques were explored to increase column efficiency by immobilizing the antibody via its C terminus, i.e., away from the antigen-binding site. In one approach, a tetra lysine tail was added, and the antibody was immobilized onto DSC-activated POROS. In the second site-directed approach, the VHH was modified with the AviTag peptide, and a biotin-residue was enzymatically incorporated at the C-terminus using the biotin ligase BirA. The biotinylated antibody was subsequently immobilized onto NeutrAvidin-derivatized POROS. A comparison of the FAC analyses, which for all three columns showed excellent linearity (R(2)>0.999), revealed that both site-directed approaches yield better results than the random immobilization; the by far highest efficiency, however, was determined for the immunoaffinity column based on AviTag-biotinylated antibody. As proof of concept, all three columns were evaluated for quantification of MTX dissolved in phosphate buffered saline (PBS). Validation using UV-detection showed excellent linearity in the range of 0.04-12MUM (R(2)>0.993). The lower limit of detection (LOD) and lower limit of quantification (LLOQ) were found to be independent of the immobilization strategy and were 40nM and 132nM, respectively. The intra- and inter-day precision was below 11.6%, and accuracy was between 90.7% and 112%. To the best of our knowledge, this is the first report of the AviTag-system in chromatography, and the first application of immunoaffinity chromatography for the analysis of MTX. PMID- 26809204 TI - Primary Care Patients with Drug Use Report Chronic Pain and Self-Medicate with Alcohol and Other Drugs. AB - BACKGROUND: Chronic pain is common among patients with drug use disorders. The prevalence of chronic pain and its consequences in primary care patients who use drugs is unknown. OBJECTIVES: To examine: 1) the prevalence of chronic pain and pain-related dysfunction among primary care patients who screen positive for drug use, and 2) the prevalence of substance use to self-medicate chronic pain in this population. DESIGN: This was a cross-sectional analysis. PARTICIPANTS: This study included 589 adult patients who screened positive for any illicit drug use or prescription drug misuse, recruited from an urban, hospital-based primary care practice. MAIN MEASURES: Both pain and pain-related dysfunction were assessed by numeric rating scales, and grouped as: (0) none, (1-3) mild, (4-6) moderate, (7 10) severe. Questions were asked about the use of substances to treat pain. KEY RESULTS: Among 589 participants, chronic pain was reported by 87% (95% CI: 84 90%), with 13% mild, 24% moderate and 50% severe. Pain-related dysfunction was reported by 74% (95% CI: 70-78%), with 15% mild, 23% moderate, and 36% severe. Of the 576 that used illicit drugs (i.e., marijuana, cocaine, and/or heroin), 51% reported using to treat pain (95% CI: 47-55% ). Of the 121 with prescription drug misuse, 81% (95% CI: 74-88%) used to treat pain. Of the 265 participants who reported any heavy drinking in the past 3 months, 38% (95% CI: 32-44%) did so to treat pain compared to 79% (95% CI: 68-90%) of the 57 high-risk alcohol users. CONCLUSIONS: Chronic pain and pain-related dysfunction were the norm for primary care patients who screened positive for drug use, with nearly one-third reporting both severe pain and severe pain-related dysfunction. Many patients using illicit drugs, misusing prescription drugs and using alcohol reported doing so in order to self-medicate their pain. Pain needs to be addressed when patients are counseled about their substance use. PMID- 26809207 TI - [The 2014 consensus conference of the ISUP on Gleason grading of prostatic carcinoma]. AB - In 2005 the International Society of Urological Pathology (ISUP) held a concensus conference on Gleason grading in order to bring this grading system up to the current state of contemporary practice; however, it became clear that further modifications on the grading of prostatic carcinoma were necessary. The International Society of Urological Pathology therefore held a further consensus conference in 2014 to clarify these points. This article presents the essential results of the Chicago grading meeting. PMID- 26809209 TI - Differentially Accumulated Proteins in Coffea arabica Seeds during Perisperm Tissue Development and Their Relationship to Coffee Grain Size. AB - Coffee is one of the most important crops for developing countries. Coffee classification for trading is related to several factors, including grain size. Larger grains have higher market value then smaller ones. Coffee grain size is determined by the development of the perisperm, a transient tissue with a highly active metabolism, which is replaced by the endosperm during seed development. In this study, a proteomics approach was used to identify differentially accumulated proteins during perisperm development in two genotypes with regular (IPR59) and large grain sizes (IPR59-Graudo) in three developmental stages. Twenty-four spots were identified by MALDI-TOF/TOF-MS, corresponding to 15 proteins. We grouped them into categories as follows: storage (11S), methionine metabolism, cell division and elongation, metabolic processes (mainly redox), and energy. Our data enabled us to show that perisperm metabolism in IPR59 occurs at a higher rate than in IPR59-Graudo, which is supported by the accumulation of energy and detoxification-related proteins. We hypothesized that grain and fruit size divergences between the two coffee genotypes may be due to the comparatively earlier triggering of seed development processes in IPR59. We also demonstrated for the first time that the 11S protein is accumulated in the coffee perisperm. PMID- 26809210 TI - Homoleptic octahedral coordination of CH3CN to Mg(2+) in the Mg[N(SO2CF3)2]2 CH3CN system. AB - X-ray diffraction and Raman spectroscopic measurements revealed a homoleptic octahedral coordination of CH3CN to Mg(2+) in the [Mg(CH3CN)6][TFSA]2 (TFSA = bis(trifluoromethylsulfonyl)imide) crystal structure and in Mg[TFSA]2/CH3CN electrolytes. PMID- 26809214 TI - Preparation and photophysical properties of fluorescent difluoroboronated beta diketones having phenanthrene moieties studied by emission and transient absorption measurements. AB - Six difluoroboronated beta-diketones having the phenanthrene skeleton (Phe@Ar) are prepared. Based on the measurements of the fluorescence quantum yields, lifetimes and transient absorption, the photophysical features of Phe@Ar are studied in comparison with those of difluoroboronated diketones having phenyl, naphthyl and anthryl moieties. beta-Diketones having 1-, 2-, 3- and 9-phenanthryl moieties (PheDKAr) were prepared as the precursor to Phe@Ar. 1-Acetylphenanthrene was synthesized by the photocyclization method as the key building block of PheDKAr having the 1-phenanthryl moiety. The counter aromatic moieties (Ar) of the prepared PheDKAr are varied with phenyl, furyl and thienyl rings (Ar = Ph, F and T, respectively) to investigate the effects of pi-conjugation on the fluorescence properties. The prepared Phe@Ars are fluorescent with appreciable fluorescence quantum yields which depend on the substitution position of the phenanthrene moiety. 3-Phe@Ph having the 3-phenanthryl moiety provides the largest fluorescence quantum yield (0.81) in acetonitrile among the Phe@Ars whereas 2-Phe@Ph having the 2-phenanthryl moiety shows the smallest fluorescence quantum yield (0.07) in acetonitrile. All the Phe@Ars show fluorescence also in the solid state, and the fluorescence spectra and quantum yields were determined. Transient absorption measurement using laser flash photolysis of the Phe@Ars revealed the triplet formation. DFT and TD-DFT calculations of Phe@Ars rationalize the dependency of the fluorescence quantum yields on the substitution position of the phenanthrene skeleton in terms of difference in the oscillator strength for the HOMO-LUMO transition. PMID- 26809216 TI - Limits of application of initiated chemiluminescence in monitoring of oncological process of mucous membrane of mouth and larynx. AB - Investigation into the limits of application of chemiluminescence (CL) methods in oncology still attracts the attention of researchers. In the present work we analyze the screening and monitoring of oncological processes (OP) in the mucous membrane of the mouth and larynx by initiated CL (ICL). Chemiluminescence has already been used by stomatologists to define the start of OP, but methods that reflect the metabolic changes in organism under cancer diagnostics still have not found their place. This work presents results of ICL on blood serum (BS) of patients with oncological diseases at different stages of medical treatment compared with those of healthy people. We found an essential metabolic difference only in types of OP that are characterized by two maxima on chemiluminograms. These OP represent only 12.81% of groups of patients with oncological diseases. The possibility to apply ICL methods to monitor operation quality and control medical treatment at different stages when the two ICL maxima are present is established. At present, the chemiluminograms with the two maxima are mostly informative, but this does not exclude the quantitative analysis of other ICL kinetic methods and is encouraging for their investigation. Any OP introduces changes in organism function and these should be reflected in the ICL. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26809217 TI - The pilT gene contributes to type III ExoS effector injection into epithelial cells in Pseudomonas aeruginosa. AB - A type IV pilus filament, mainly composed of PilA, is retracted by the driving power generated by PilT and PilU ATPases. pilA is required for injection of type III ExoS effectors into epithelial cells thereby facilitating Pseudomonas aeruginosa penetration through the epithelial barrier by impairing the defense function of tight junctions. Here, we examined whether the pilT and pilU of the P. aeruginosa PAO1 strain are required for ExoS injection into epithelial cells. We measured the quantity of ExoS injected into epithelial cells, and found that within such cells its quantity decreased by 80% (DeltapilA strain), 75% (DeltapilT strain), and 30% (DeltapilU strain) compared with the wild-type strain. pilT deficiency decreased the disruption of human epithelial colorectal adenocarcinoma (Caco-2) cell monolayers to the same extent as that of pilA and exoS deficiency, whereas pilU deficiency decreased disruption of the monolayers less than deficiency of the other genes. pilT and pilU deficiency decreased bacterial penetration of the Caco-2 cell monolayers to the same level as pilA and exoS deficiency. Our data showed that the pilU gene expression level was reduced in the PAO1 strain after adhesion to Caco-2 cell surfaces, but the expression levels of the pilA and pilT genes did not change. We conclude that P. aeruginosa injects ExoS into cells through the function of type IV pilus retraction, and that pilT makes a greater contribution to this process than pilU. PMID- 26809218 TI - Pharmacokinetics and brain penetration of carbapenems in mice. AB - An adverse effect associated with the administration of carbapenems is central nervous system (CNS) toxicity, with higher brain concentrations of carbapenems being linked to an increased risk of seizures. However, the pharmacokinetics and brain penetration of carbapenems have not yet been examined. Thus, the aim of this in vivo investigation was to determine the pharmacokinetics and brain penetration of carbapenems in mice. Blood samples and brain tissue samples were obtained 10, 20, 30, 60, and 120 min after the subcutaneous administration of carbapenems (91 mg/kg). We obtained the following values for the pharmacokinetic parameters of carbapenems in mice: 1.20-1.71 L/h/kg for CLtotal/F, 1.41-2.03 h( 1) for Ke, 0.34-0.51 h for T1/2, 0.66-0.95 L/kg for Vss/F, 0.49-0.73 h for MRT, 83.46-110.58 MUg/mL for Cmax, plasma, and 0.28-0.83 MUg/g for Cmax, brain tissue. The AUC0-infinity of the carbapenems tested in plasma were in the following order: doripenem > meropenem > biapenem > imipenem, and in brain tissue were: imipenem > doripenem > meropenem > biapenem. The degrees of brain tissue penetration, defined as the AUC0-infinity, brain tissue/fAUC0-infinity, plasma ratio, were 0.016 for imipenem, 0.004 for meropenem, 0.002 for biapenem, and 0.008 for doripenem. The results of the present study demonstrated that, of the carbapenems examined, imipenem penetrated brain tissue to the greatest extent. PMID- 26809220 TI - Complete-arch implant-supported monolithic zirconia fixed dental prostheses: A systematic review. AB - STATEMENT OF PROBLEM: Monolithic zirconia prostheses are emerging as a promising option in the implant-based rehabilitations of edentulous patients, yet their clinical performance is not fully documented. PURPOSE: The purpose of this systematic review was to assess the clinical performance of complete-arch implant supported monolithic zirconia fixed dental prostheses. MATERIAL AND METHODS: The electronic databases PubMed, Science Direct, and Cochrane Library were searched for clinical studies on complete-arch implant-supported monolithic zirconia fixed dental prostheses. Human studies with a mean follow-up of at least 1 year and published in an English-language peer-reviewed journal up to June 2015 were included. Two independent examiners conducted the search and the review process. RESULTS: The search generated 903 titles. Eighteen qualifying studies were retrieved for full-text evaluation. Nine studies were included on the basis of preestablished criteria. Eight studies reported satisfactory clinical and esthetic outcomes. One study demonstrated prosthesis failure. Clinical studies are lacking on the long-term outcome of complete-arch implant-supported monolithic zirconia prostheses. CONCLUSIONS: Complete-arch dental implant restoration with monolithic zirconia is associated with high short-term success. Despite the many advantages and short-term favorable reports, studies of longer duration are necessary to validate the broad application of this therapy. PMID- 26809219 TI - Use of matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry for bacterial monitoring in routine analysis at a drinking water treatment plant. AB - The study of bacterial communities throughout a drinking water treatment plant could provide a basic understanding of the effects of water processing that could then be used to improve the management of such plants. However, it is necessary to develop new analytical techniques that are sufficiently efficient, robust and fast for their effective and useful application in routine analysis. The aim of this study is therefore to assess the performance of matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), as compared to the PhenePlateTM system, for routine analysis in a drinking water treatment plant. To this end we studied a total of 277 colonies isolated in different seasons and from different points throughout the water treatment process, including: raw water, sand filtration, ultrafiltration, reverse osmosis and chlorination. The colonies were analysed using MALDI-TOF MS by direct deposition of the cells on the plate. The colonies were also biochemically fingerprinted using the PhenePlateTM system, clustered according to their similarity and a representative strain was selected for 16S rRNA gene sequencing and API(r) gallery-based identification. The use of MALDI-TOF MS was reliable compared to the PhenePlateTM system and has the advantage of being faster and relatively cheap. Bacteria typing by MALDI-TOF MS is therefore a promising method to replace conventional routine phenotypic methods for the identification of bacteria in drinking water laboratories, thanks to its robustness. The major limiting factor for MALDI-TOF MS is the lack of a suitable mass spectra database; although each laboratory can develop its own library. This methodology will provide a tracking tool for companies to use in risk management and the detection of possible failures in both the water treatment processes and the distribution network, as well as offering characterization of the intrinsic microbial populations. PMID- 26809221 TI - Effects of surface treatments on the translucency, opalescence, and surface texture of dental monolithic zirconia ceramics. AB - STATEMENT OF PROBLEM: Surface polishing or glazing may increase the appearance of depth of monolithic zirconia restorations. PURPOSE: The purpose of this in vitro study was to investigate the effects of surface treatments on the translucency, opalescence, and surface texture of dental monolithic zirconia ceramics. MATERIAL AND METHODS: Forty-five monolithic zirconia specimens (16.3*16.4*2.0 mm) were divided into groups I to V, according to the number of colorings each received. Each group was then divided into 3 subgroups (n=3) according to the surface treatment: N=no treatment; P=polished; and G=glazed. CIElab color coordinates were obtained relative to D65 on a reflection spectrophotometer. The translucency parameter (TP) and opalescence parameter (OP) were calculated. One specimen per subgroups I and V was selected for evaluation of surface roughness (Ra) and was examined with scanning electron microscopy (SEM). Data were analyzed with 2-way ANOVA and pairwise comparisons (alpha=.05). Statistical powers were verified to evaluate results (alpha=.05). RESULTS: The interaction effects of surface treatments combined with the number of colorings were significant for TP, OP, and Ra (P<.001), as follows: Ra=partial eta squared [etap(2)]=.928; OP etap(2)=.184; and TP etap(2)=.144. No significant differences between TP were found among surface treatments in most groups (P>.05), whereas glazing significantly decreased OP and Ra in most groups. SEM images demonstrated that surface treatments affected the surface texture of monolithic zirconia ceramics. CONCLUSIONS: Surface treatments combined with coloring strongly affect the surface texture of dental monolithic zirconia ceramics. PMID- 26809222 TI - Completely digital approach to fabricating a crown under an existing partial removable dental prosthesis by using an intraoral digital scanner in a single appointment. AB - Retrofitting a crown to an existing partial removable dental prosthesis (PRDP) is difficult, labor intensive, and time consuming. This article presents an alternative technique for fabricating a crown under an existing PRDP by using an intraoral digital scanner and computer-assisted design and computer-aided manufacturing (CAD/CAM) technology. This technique involves less human error and provides a well-fitting restoration. PMID- 26809223 TI - Combining guided alveolar ridge reduction and guided implant placement for all-on 4 surgery: A clinical report. AB - Immediate restoration with the all-on-4 concept has become an established treatment option. The technique involves alveoloplasty before implant placement to provide space for the prosthetic components and to provide a platform on which dental implants can be placed in clinical situations where a knife-edge alveolar ridge is present. Guided implant surgery involves the fabrication of a guide by using data from cone-beam computed tomography (CBCT) and implant surgery performed without flap reflection. In the presented technique, a printed cast based on a CBCT is used to fabricate a guide for both alveolar ridge reduction and guided implant surgery. The alveolar ridge reduction and implant surgery are virtually simulated in the laboratory to provide space for the restorative components and to avoid critical anatomic landmarks (mental nerve or perforation of the lingual mandibular plate). The described surgical guide enables guided alveolar ridge reduction and guided implant placement where the implant placement performed in the laboratory can be duplicated clinically during implant surgery. PMID- 26809229 TI - [A Dynamic Model to Estimate the Budget Impact of a Pneumococcal Vaccination Program in a 65 Year-old immunocompetent Spanish Cohort with 13-Valent Pneumococcal Conjugate Vaccine]. AB - OBJECTIVE: To estimate the 5-year clinical and economic impact of a pneumococcal vaccination program on immunocompetent population aged 65-year-old in Spain. METHODS: A 5 year dynamic model based on differential equations was built for the conceptualization of the burden of pneumococcal disease (PD) on a 65 year-old cohort. A 36.5% of the cohort was vaccinated with an expected efficacy rate of 52.5% as observed in the CAPITA study. The serotype vaccination coverage used was 63.4% (CAPA study), the incidence of pneumococcal disease was 162.2 per 100,000 cases per year (CMBD 2010-2013) and a rate of vaccinated subjects previously from the start of the model of 0.99%. The study used the perspective of The National Health System, and included the costs associated to PD and the conjugate vaccine laboratory selling price. RESULTS: In a 5 years-period, the vaccination with 13 valent pneumococcal conjugate vaccine is expected to avoid 10,360 cases of pneumococcal disease (7,411 in-patient pneumonias) and 699 deaths (14,736 Life Years Gained) in the 65 year old cohort. Vaccination costs of 36.5 million euros would be completely offset by medical cost reduction of 41.5 million euros, yielding to a net saving of 3.8 million constant euros (4.9 million undiscounted). CONCLUSIONS: PCV13 vaccination targeting the cohort of 65 year-old immunocompetent Spanish adults is expected to result in net savings for the National Health System, while decreasing disease burden and averting a substantial number of related deaths. PMID- 26809225 TI - Objective sleep disturbances are associated with greater waking resting-state connectivity between the retrosplenial cortex/ hippocampus and various nodes of the default mode network. AB - BACKGROUND: Psychological models highlight the bidirectional role of self referential processing, introspection, worry and rumination in the development and maintenance of insomnia; however, little is known about the underlying neural substrates. Default mode network (DMN) functional connectivity has been previously linked to these cognitive processes. METHODS: We used fMRI to investigate waking DMN functional connectivity in a well-characterized sample of patients with primary insomnia (PI) and good sleeper controls. RESULTS: We included 20 patients with PI (8 men and 12 women, mean age 42.7 +/- 13.4 yr) and 20 controls (8 men and 12 women, mean age 44.1 +/- 10.6 yr) in our study. While no between-group differences in waking DMN connectivity were observed, exploratory analyses across all participants suggested that greater waking connectivity between the retrosplenial cortex/hippocampus and various nodes of the DMN was associated with lower sleep efficiency, lower amounts of rapid eye movement sleep and greater sleep-onset latency. LIMITATIONS: Owing to the cross sectional nature of the study, conclusions about causality cannot be drawn. CONCLUSION: As sleep disturbances represent a transdiagnostic symptom that is characteristic of nearly all psychiatric disorders, our results may hold particular relevance to previous findings of increased DMN connectivity levels in patients with psychiatric disorders. PMID- 26809224 TI - Purines: forgotten mediators in traumatic brain injury. AB - Recently, the topic of traumatic brain injury has gained attention in both the scientific community and lay press. Similarly, there have been exciting developments on multiple fronts in the area of neurochemistry specifically related to purine biology that are relevant to both neuroprotection and neurodegeneration. At the 2105 meeting of the National Neurotrauma Society, a session sponsored by the International Society for Neurochemistry featured three experts in the field of purine biology who discussed new developments that are germane to both the pathomechanisms of secondary injury and development of therapies for traumatic brain injury. This included presentations by Drs. Edwin Jackson on the novel 2',3'-cAMP pathway in neuroprotection, Detlev Boison on adenosine in post-traumatic seizures and epilepsy, and Michael Schwarzschild on the potential of urate to treat central nervous system injury. This mini review summarizes the important findings in these three areas and outlines future directions for the development of new purine-related therapies for traumatic brain injury and other forms of central nervous system injury. In this review, novel therapies based on three emerging areas of adenosine-related pathobiology in traumatic brain injury (TBI) were proposed, namely, therapies targeting 1) the 2',3'-cyclic adenosine monophosphate (cAMP) pathway, 2) adenosine deficiency after TBI, and 3) augmentation of urate after TBI. PMID- 26809230 TI - Could "red cell distribution width" predict COPD severity? AB - BACKGROUND AND OBJECTIVES: Erythrocyte morphology changes not only by primary hematological diseases but also by systemic inflammation, ineffective erythropoiesis and nutritional deficiencies. Red blood cell distribution width (RDW) is a parameter reflecting erythrocyte morphology. We aimed to investigate the relationship of RDW with chronic obstructive pulmonary disease (COPD) stages, BODE index and survival in COPD patients. METHODS: Medical records of 385 COPD patients between July 2004 and November 2005 were studied retrospectively. Demographic features, BODE index factors and oxygen saturation were recorded. Survival analysis of all patients by 2014 was performed. Measured RDW values at the time of the inclusion were evaluated. RESULTS: Mean age of the patients was 65.6+/-9.6 years. Distribution of the COPD stages of the patients were stage 1: 16%, stage 2: 52%, stage 3: 26%, stage 4: 6%. RDW was found significantly different between stages. The highest RDW was observed in the very severe stage (p<0.001). Median of BODE index was 1 (0-3). As the BODE index increased RDW also increased (p<0.001). When the patients were grouped according to the laboratory upper limit of RDW, survival rate was 31% in the RDW >14.3% group and 75% in the RDW <14.3% group. CONCLUSION: The variability in the size of circulating erythrocytes increases as the COPD severity progresses. Therefore, a simple and noninvasive test, such as RDW, might be used as a biomarker in the evaluation of the severity of COPD. At the same time, there seems to be a correlation between the survival of COPD patients and RDW. PMID- 26809232 TI - Prevalence of non-adherence among psychiatric patients in Jordan, a cross sectional study. AB - BACKGROUND: It has been estimated that up to 50% of any patient population is at least partially non-adherent to their prescribed treatment. Identifying barriers to adherence is required to develop effective interventions for psychiatric patients. OBJECTIVE: To explore the prevalence and factors of non-adherence among psychiatric patients present at four psychiatric clinics. METHOD: A cross sectional questionnaire-based study. A sample of psychiatric patients attending outpatient psychiatric clinics was enrolled between March and April 2011. RESULTS: A total of 243 psychiatric patients took part in this study with the majority of patients (92.5%) being prescribed more than one psychiatric disorder. The majority (64.2%) of the patients was classified as non-adherent according to the Morisky adherence questionnaire and forgetfulness was the most prevalent reason for that. CONCLUSIONS: Non-adherence is a common and important issue among psychiatric patients. Polypharmacy, safety concerns and lack of insight towards the prescribed treatment were reported as the main reasons of non-adherence. PMID- 26809233 TI - High-Throughput LC-MS/MS Method for Direct Quantification of Glucuronidated, Sulfated, and Free Enterolactone in Human Plasma. AB - Sulfation and glucuronidation constitute a major pathway in humans and may play an important role in biological activity of metabolites including the enterolignan, enterolactone. Because the aromatic structure of enterolactone has similarities to steroid metabolites, it was hypothesized that enterolactone may protect against hormone-dependent cancers. This led to numerous epidemiological studies. In this context, there has been a demand for rapid, sensitive, high throughput methods to measure enterolactone in biofluids. Different methods have been developed using GC-MS, HPLC, LC-MS/MS and a fluoroimmunoassay; however, most of these methods measure the total concentration of enterolactone, without any specification of its conjugation pattern. Here for the first time we present a high-throughput LC-MS/MS method to quantify enterolactone in its intact form as glucuronide, sulfate, and free enterolactone. The method has shown good accuracy and precision at low concentration and very high sensitivity, with LLOQ for enterolactone sulfate at 16 pM, enterolactone glucuronide at 26 pM, and free enterolactone at 86 pM. The short run time of 2.6 min combined with simple sample clean up and high sensitivity make this method attractive for the high-throughput of samples needed for epidemiological studies. Finally, we have adapted the new method to quantify enterolactone and its conjugates in 3956 plasma samples from an epidemiological study. We found enterolactone glucuronide to be the major conjugation form and that conjugation pattern was similar between men and women. PMID- 26809234 TI - Mortality, cancer incidence, and survival in parents after bereavement. AB - PURPOSE: The study objective was to investigate whether child loss is related to mortality, cancer incidence, and cancer survival in parents. METHODS: We used a population-based birth cohort (1964-1976) in Jerusalem and ascertained mortality (average follow-up of 39.1 years) and any cancer (average follow-up of 35.6 years) among parents who lost a child (2838 mothers and 2532 fathers) and among nonbereaved parents (38,212 mothers and 36,433 fathers). We also assessed mortality among parents with cancer. Time-dependent Cox models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Overall mortality rates among bereaved parents were modestly increased when compared with nonbereaved parents (HR = 1.18, 95% CI: 1.05-1.32 in mothers; HR = 1.10, 95% CI: 1.01-1.20 in fathers). Hazard models indicated a significant relationship between bereavement and deaths from coronary heart disease in mothers (HR = 1.90, 95% CI: 1.23-2.95) and circulatory causes in both parents (HR = 1.69; 95% CI: 1.22-2.34 in mothers and HR = 1.25; 95% CI: 1.02-1.54 in fathers). Bereavement was not associated with parental risk of cancer disease and with survival from cancer. The association between bereavement and parental overall mortality was similar in the different parental sociodemographic characteristics. We observed a decrease in HRs for parental mortality associated with bereavement, with increasing time since the death of the child (HRs = 9-10, 0-3 years; HRs = 0.9-1.0, 9+ years; P(heterogeneity) <= 3 * 10(-32)). A similar decrease in HRs was observed for parental survival from cancer (HRs = 6.7-8.7, 0 3 years; HRs = 0.9-1.0, 9+ years). CONCLUSIONS: Our study suggests that child loss was associated with slightly increased risk of all-cause and circulatory mortality in parents but not with incidence of cancer and cancer survival. The considerable increased parental mortality during a short period after child loss support the involvement of pathways related to psychological stress. PMID- 26809235 TI - Augmented reality visualization in head and neck surgery: an overview of recent findings in sentinel node biopsy and future perspectives. AB - "Augmented reality visualisation", in which the site of an operation is merged with computer-generated graphics, provides a way to view the relevant part of the patient's body in better detail. We describe its role in relation to sentinel lymph node biopsy (SLNB), current advancements, and future directions in the excision of tumours in early-stage cancers of the head and neck. PMID- 26809236 TI - Lemierre syndrome: headache and proptosis as unusual presentation of dental infection by Gemella morbillorum. PMID- 26809237 TI - Do you mind if I vape? Immediate effects of electronic cigarettes on perfusion in buccal mucosal tissue--a pilot study. AB - The association between smoking and postoperative complications is compounded in patients who have oral and maxillofacial operations by an additional local effect, and patients often continue to smoke after operation despite advice to stop. Recent studies have suggested that nicotine may reduce inflammation and improve angiogenesis, so topical application may be beneficial for smokers. The electronic cigarette is increasing in popularity and more patients ask whether they can vape after operation. We investigated the effect of electronic cigarettes (of which half contained nicotine and half did not) on blood flow in the buccal mucosa in 10 volunteers immediately after vaping. Smokers were excluded as this was considered an additional variable in a small pilot study and our Trust has a no-smoking policy. After vaping for 5 minutes, capillary blood flow was measured in the buccal mucosa at 5-minute intervals using a laser Doppler probe, and the results were expressed as arbitrary perfusion units. There was a wide variation in results and a small but significant rise (p=0.008) as a result of nicotine vaping, but these fell to the same levels as before within 30 minutes. Electronic cigarettes may have an effect on blood flow to the oral mucosa, although further studies are needed to show whether they improve healing time after operation. Additional work is also needed to compare them with cigarettes. PMID- 26809239 TI - BMPR2 gene therapy for PAH acts via Smad and non-Smad signalling. AB - BACKGROUND AND OBJECTIVE: Pulmonary arterial hypertension (PAH) continues to be a fatal disease and is associated with downregulation of bone morphogenetic protein receptor type-2 (BMPR2). Our approach is to upregulate BMPR2 in the pulmonary vasculature allowing us to examine the changes in endothelial cell signalling and better understand what pathways are altered when disease is attenuated using this treatment approach. METHODS: We used gene delivery of BMPR2 to human pulmonary endothelial cells to investigate downstream signalling, then assessed the impact of this approach on downstream signalling in vivo in rats with PAH using the monocrotaline (MCT) model. RESULTS: Gene delivery of BMPR2 leads to an increase in BMPR2 protein expression, and this is associated with increased Smad1/5/8 and reduced Smad2/3 signalling. Additionally, we have found that BMPR2 modulation has effects on non-Smad signalling with increases found in phosphoinositide-3 kinase (PI3K) and a decrease in phosphorylated-p38-mitogen activated protein kinase (p38 MAPK) in vivo. These findings are associated with amelioration of PAH (reduced right ventricular, mean pulmonary artery pressures and Fulton Index). CONCLUSION: These results indicate that the therapeutic effect of BMPR2 gene delivery on PAH is associated with a switch between TGF-beta-Smad2/3 signalling to BMPR2 Smad1/5/8 signalling. This supports the further development of this treatment approach. PMID- 26809240 TI - Early Candidate Biomarkers of Non-Small Cell Lung Cancer Are Screened and Identified in Premalignant Lung Lesions. AB - A specific protein profile that accompanies neoplastic transformation in the premalignant airway epithelium could provide an opportunity for early diagnosis of lung cancer. The aim of this study was to screen and identify early candidate biomarkers of non-small cell lung cancer. Thirteen non-small cell lung cancer samples were obtained within 30 minutes after a surgical resection. Laser capture microdissection was performed to enrich the normal lung cell and squamous metaplasia or atypical adenomatous hyperplasia cell populations. The resulting tandem mass spectrum was automatically searched for proteins against International Protein Index (IPI) human protein database using the TurboSEQUEST searching engine. The molecular function and biological processes of identified proteins were determined based on universal bioinformatics tools. The 2 proteins of interest, focal adhesion kinase and C-terminal Src kinase, were validated using Western blot method. A total of 863 proteins were identified by automatically searching the tandem mass spectrum, among which 427 were dysregulated expression in premalignant airway epithelium compared with those of normal lung cells. The 427 proteins were mainly distributed in 24 sorts of cellular components, 22 molecular function, 15 biological processes, and 10 significant perturbations of pathways. The most significant network included 48 genes and was related to energy production, cell cytoskeleton, cell adhesion, metabolism, oxidative stress, and small molecule biochemistry. Focal adhesion kinase and C-terminal Src kinase were significantly overexpressed in premalignant lung lesion cells compared with the normal lung cells in 13 cases. We identified that there were 427 proteins involved in non-small cell lung cancer carcinogenic process and confirmed the key biological pathways in premalignant lung tissue. The significantly upregulated focal adhesion kinase and C-terminal Src kinase could be considered as molecular biomarkers for early diagnosis and prognosis of non-small cell lung cancer. PMID- 26809241 TI - Receiving Support, Giving Support, Neighborhood Conditions, and Waist/Hip Ratios. AB - Obesity is a major health problem in the USA, and as a result, it is important to identify the factors that help people keep their body weight within healthy limits. The purpose of this study was to see whether receiving support at church and giving support at church buffer (i.e., moderate) the effects of living in rundown neighborhoods on a key marker of obesity-waist/hip ratios (WHR). The data are provided from a recent nationwide survey of people age 18 and older (N = 1456). The findings reveal that giving support to fellow church members tends to offset the effects of living in dilapidated neighborhoods on WHR. In contrast, receiving support from coreligionists does not appear to perform a similar stress moderating function. The theoretical underpinnings of providing support at church are discussed. PMID- 26809242 TI - Role of Religion in Preventing Youth Sexual Activity in Malaysia: A Mixed Methods Study. AB - One of the popular approaches of preventing youth sexual activity in Malaysia is using religion to promote premarital sexual abstinence. Despite this intervention, youth continue to practise premarital sex. Thus, the purpose of this exploratory mixed methods study was to understand the role of religion on sexual activity among college students in Klang Valley, Malaysia. A self administered questionnaire survey to determine the relationship between religiosity and youth sexual activity was carried out on 1026 students recruited from 12 randomly selected colleges. Concurrently, face-to-face interviews were conducted on 15 students to explore how religiosity had influenced their decision on sexual activity. The survey data were analysed using logistic regression, while the qualitative data from the interviews were examined using thematic analysis with separate analysis for each gender. Both quantitative and qualitative results were then compared and integrated. Religious activity significantly reduced the risk of continuing sexual activity among female students (AOR = 0.67, CI = 0.47, 0.95, p = 0.02) but not male students. There was no significant relationship of religious affiliation and intrinsic religiosity (inner faith) to sexual activity by gender. Having faith in religion and strong sexual desire were the main themes that explained participants' sexual behaviour. Engaging in religious activity might be effective at preventing female students from being sexually active. However, when sexual urges and desires are beyond control, religiosity might not be effective. PMID- 26809243 TI - The PROMESA-protocol: progression rate of multiple system atrophy under EGCG supplementation as anti-aggregation-approach. AB - Formation of toxic alpha-synuclein oligomers appears to be a key underlying pathological mechanism of synucleinopathies such as Parkinson's disease or multiple system atrophy (MSA). Given that Epigallocatechin-gallate has been shown to inhibit alpha-synuclein aggregation, it might represent a causal treatment option. Therefore, we set out to evaluate the safety, tolerability and a potential disease-modifying effect of Epigallocatechin-gallate in patients with MSA after 48 weeks of treatment. Power calculation was performed on existing natural history data on the progression of the Unified MSA Rating Scale as primary readout parameter. To assess the efficacy of Epigallocatechin-gallate versus placebo regarding the reduction of disease progression measured during the study period (80 % power, 5 % p level, 50 % effect size) 36 patients per group are needed. Considering a drop-out rate of 20 % a total of 86 patients will be recruited in this multicentre study. These data provide a solid rationale to investigate whether supplementation of Epigallocatechin-gallate can delay the progression of the MSA-related disability. PMID- 26809244 TI - Elotuzumab: First Global Approval. AB - Elotuzumab (EmplicitiTM) is a humanised IgG1 monoclonal antibody developed by Bristol-Myers Squibb (BMS) and AbbVie that has been approved as combination therapy with lenalidomide and dexamethasone for relapsed/refractory multiple myeloma in the US. Elotuzumab binds to the cell surface receptor signalling lymphocytic activation molecule F7 (SLAMF7), which is selectively expressed on myeloma cells and natural killer cells, leading to antibody-dependent cellular cytotoxicity and direct natural killer cell activation. In a phase III clinical trial, addition of elotuzumab to lenalidomide and dexamethasone therapy in patients with relapsed/refractory multiple myeloma was associated with a significant improvement in progression-free survival and overall response rate. This article summarizes the milestones in the development of elotuzumab leading to this first approval for relapsed/refractory multiple myeloma. PMID- 26809246 TI - Tumor characteristics and therapy of elderly patients with breast cancer. AB - INTRODUCTION: Elderly breast cancer patients aged >=75 years are underrepresented in most studies. Therefore, data on cancer characteristics, adjuvant treatment and survival in elderly patients are missing. PATIENTS AND METHODS: In this retrospective study, we compared tumor characteristics and adjuvant therapy in 973 women with invasive, non-metastasized breast cancer aged >=75 years with 3377 younger postmenopausal patients (50-74 years old). Time dynamics of tumor characteristics were investigated, comparing two observation periods between the years 2000-2004 versus 2005-2008. RESULTS: Compared to younger women, older patients were more often treated with mastectomy and less likely to receive adjuvant treatment. Although the overall survival rate increased over the observation period in both age groups, the older study group was characterized by shorter disease-free survival. Additionally, we observed an increase in about 1.65 years in the age at diagnosis as well as an increasing rate of breast conserving surgery and sentinel lymph node biopsy for the whole study population between 2000 and 2008. Furthermore, we found a reduction in the proportion of estrogen receptor-positive tumors in the younger women and a decrease in G3 tumors in both age groups over the study time. CONCLUSION: The older group's reduced disease-free survival could be explained by the tumor characteristics and differences in the adjuvant treatment. Remarkably, elderly women are more likely to be overtreated surgically while being undertreated in terms of adjuvant therapy. PMID- 26809247 TI - Randomized, controlled, two-arm, interventional, multicenter study on risk adapted damage control orthopedic surgery of femur shaft fractures in multiple trauma patients. AB - BACKGROUND: Long bone fractures, particularly of the femur, are common in multiple-trauma patients, but their optimal management has not yet been determined. Although a trend exists toward the concept of "damage control orthopedics" (DCO), current literature is inconclusive. Thus, a need exists for a more specific controlled clinical study. The primary objective of this study was to clarify whether a risk-adapted procedure for treating femoral fractures, as opposed to an early definitive treatment strategy, leads to an improved outcome (morbidity and mortality). METHODS/DESIGN: The study was designed as a randomized controlled multicenter study. Multiple-trauma patients with femur shaft fractures and a calculated probability of death of 20 to 60 % were randomized to either temporary fracture fixation with external fixation and defined secondary definitive treatment (DCO) or primary reamed nailing (early total care). The primary objective was to reduce the extent of organ failure as measured by the maximum sepsis-related organ failure assessment (SOFA) score. RESULTS: Thirty four patients were randomized to two groups of 17 patients each. Both groups were comparable regarding sex, age, injury severity score, Glasgow Coma Scale, prothrombin time, base excess, calculated probability of death, and other physiologic variables. The maximum SOFA score was comparable (nonsignificant) between the groups. Regarding the secondary endpoints, the patients with external fixation required a significantly longer ventilation period (p = 0.049) and stayed on the intensive care significantly longer (p = 0.037), whereas the in hospital length of stay was balanced for both groups. Unfortunately, the study had to be terminated prior to reaching the anticipated sample size because of unexpected low patient recruitment. CONCLUSIONS: Thus, the results of this randomized study reflect the ambivalence in the literature. No advantage of the damage control concept could be detected in the treatment of femur fractures in multiple-trauma patients. The necessity for scientific evaluation of this clinically relevant question remains. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10321620 Date assigned: 9 February 2007. PMID- 26809245 TI - Management of Neuropsychiatric Systemic Lupus Erythematosus: Current Approaches and Future Perspectives. AB - Neuropsychiatric systemic lupus erythematosus (NPSLE) is a generic definition referring to a series of neurological and psychiatric symptoms directly related to systemic lupus erythematosus (SLE). NPSLE includes heterogeneous and rare neuropsychiatric (NP) manifestations involving both the central and peripheral nervous system. Due to the lack of a gold standard, the attribution of NP symptoms to SLE represents a clinical challenge that obligates the strict exclusion of any other potential cause. In the acute setting, management of these patients does not differ from other non-SLE subjects presenting with the same NP manifestation. Afterwards, an individualized therapeutic strategy, depending on the presenting manifestation and severity of symptoms, must be started. Clinical trials in NPSLE are scarce and most of the data are extracted from case series and case reports. High-dose glucocorticoids and intravenous cyclophosphamide remain the cornerstone for patients with severe symptoms that are thought to reflect inflammation or an underlying autoimmune process. Rituximab, intravenous immunoglobulins, or plasmapheresis may be used if response is not achieved. When patients present with mild to moderate NP manifestations, or when maintenance therapy is warranted, azathioprine and mycophenolate may be considered. When symptoms are thought to reflect a thrombotic underlying process, anticoagulation and antiplatelet agents are the mainstay of therapy, especially if antiphospholipid antibodies or antiphospholipid syndrome are present. Recent trials on SLE using new biologicals, based on newly understood SLE mechanisms, have shown promising results. Based on what we currently know about its pathogenesis, it is tempting to speculate how these new therapies may affect the management of NPSLE patients. This article provides a comprehensive and critical review of the literature on the epidemiology, pathophysiology, diagnosis, and management of NPSLE. We describe the most common pharmacological treatments used in NPSLE, based on both a literature search and our expert opinion. The extent to which new drugs in the advanced development of SLE, or the blockade of new targets, may impact future treatment of NPSLE will also be discussed. PMID- 26809248 TI - Ventral and Dorsal Striatum Networks in Obesity: Link to Food Craving and Weight Gain. AB - BACKGROUND: The food addiction model proposes that obesity overlaps with addiction in terms of neurobiological alterations in the striatum and related clinical manifestations (i.e., craving and persistence of unhealthy habits). Therefore, we aimed to examine the functional connectivity of the striatum in excess-weight versus normal-weight subjects and to determine the extent of the association between striatum connectivity and individual differences in food craving and changes in body mass index (BMI). METHODS: Forty-two excess-weight participants (BMI > 25) and 39 normal-weight participants enrolled in the study. Functional connectivity in the ventral and dorsal striatum was indicated by seed based analyses on resting-state data. Food craving was indicated with subjective ratings of visual cues of high-calorie food. Changes in BMI between baseline and 12 weeks follow-up were assessed in 28 excess-weight participants. Measures of connectivity in the ventral striatum and dorsal striatum were compared between groups and correlated with craving and BMI change. RESULTS: Participants with excess weight displayed increased functional connectivity between the ventral striatum and the medial prefrontal and parietal cortices and between the dorsal striatum and the somatosensory cortex. Dorsal striatum connectivity correlated with food craving and predicted BMI gains. CONCLUSIONS: Obesity is linked to alterations in the functional connectivity of dorsal striatal networks relevant to food craving and weight gain. These neural alterations are associated with habit learning and thus compatible with the food addiction model of obesity. PMID- 26809250 TI - Attention-Deficit/Hyperactivity Disorder in Offspring of Mothers With Inflammatory and Immune System Diseases. AB - BACKGROUND: Prenatal inflammatory mechanisms may play a role in the pathogenesis of psychiatric disorders and could be relevant for attention deficit/hyperactivity disorder (ADHD). We investigated maternal chronic somatic diseases with immune components as possible risk factors for ADHD in offspring. METHODS: We performed a population-based nested case-control study by linking data from longitudinal Norwegian registers. We included all individuals born during the period 1967-2008 and alive at record linkage (2012). Individuals receiving ADHD medication during the years 2004-2012 were defined as patients with ADHD (N = 47,944), and all remaining individuals (N = 2,274,713) were defined as control subjects. The associations between maternal diseases and ADHD in offspring were analyzed using logistic regression models. RESULTS: The following chronic diseases with immune components were related to ADHD in offspring: multiple sclerosis (adjusted odds ratio [OR] = 1.8; 95% confidence interval [CI] = 1.2-2.5), rheumatoid arthritis (adjusted OR = 1.7; 95% CI = 1.5 1.9), type 1 diabetes (adjusted OR = 1.6; 95% CI = 1.3-2.0), asthma (adjusted OR = 1.5; 95% CI = 1.4-1.6), and hypothyroidism (adjusted OR = 1.2; 95% CI = 1.1 1.4). In contrast, chronic hypertension and type 2 diabetes showed no significant associations. Estimates were almost unchanged with additional adjustment for parental ADHD, infant birth weight, and gestational age. Although point estimates for male and female offspring were different for some diseases (e.g., maternal asthma [adjusted OR = 1.7; 95% CI = 1.5-1.8 for female offspring and adjusted OR = 1.5; 95% CI = 1.4-1.6 for male offspring]), none of the associations differed significantly by offspring sex. CONCLUSIONS: Several maternal somatic diseases with immune components were found to increase the risk of ADHD in offspring. The associations could involve several causal pathways, including common genetic predisposition and environmental factors, and increased insight into the mechanisms behind these relationships could enhance our understanding of the etiology of ADHD. PMID- 26809249 TI - Hippocampal Neuroinflammation, Functional Connectivity, and Depressive Symptoms in Multiple Sclerosis. AB - BACKGROUND: Depression, a condition commonly comorbid with multiple sclerosis (MS), is associated more generally with elevated inflammatory markers and hippocampal pathology. We hypothesized that neuroinflammation in the hippocampus is responsible for depression associated with MS. We characterized the relationship between depressive symptoms and hippocampal microglial activation in patients with MS using the 18-kDa translocator protein radioligand [(18)F]PBR111. To evaluate pathophysiologic mechanisms, we explored the relationships between hippocampal neuroinflammation, depressive symptoms, and hippocampal functional connectivities defined by resting-state functional magnetic resonance imaging. METHODS: The Beck Depression Inventory (BDI) was administered to 11 patients with MS and 22 healthy control subjects before scanning with positron emission tomography and functional magnetic resonance imaging. We tested for higher [(18)F]PBR111 uptake in the hippocampus of patients with MS relative to healthy control subjects and examined the correlations between [(18)F]PBR111 uptake, BDI scores, and hippocampal functional connectivities in the patients with MS. RESULTS: Patients with MS had an increased hippocampal [(18)F]PBR111 distribution volume ratio relative to healthy control subjects (p = .024), and the hippocampal distribution volume ratio was strongly correlated with the BDI score in patients with MS (r = .86, p = .006). Hippocampal functional connectivities to the subgenual cingulate and prefrontal and parietal regions correlated with BDI scores and [(18)F]PBR111 distribution volume ratio. CONCLUSIONS: Our results provide evidence that hippocampal microglial activation in MS impairs the brain functional connectivities in regions contributing to maintenance of a normal affective state. Our results suggest a rationale for the responsiveness of depression in some patients with MS to effective control of brain neuroinflammation. Our findings also lend support to further investigation of the role of inflammatory processes in the pathogenesis of depression more generally. PMID- 26809252 TI - Selecting Patients with Ovarian Cancer for Germline BRCA Mutation Testing: Findings from Guidelines and a Systematic Literature Review. AB - INTRODUCTION: One of the most significant risk factors for the development of ovarian cancer (OC) is a genetic mutation in BRCA1 (breast cancer gene 1) or BRCA2. Here we describe the impact of previous and current guidance on BRCA testing practices and provide evidence about which characteristics best identify patients with OC and an underlying germline BRCA mutation. METHODS: A search was conducted for guidelines recommending genetic testing to identify constitutional pathogenic mutations in the BRCA genes. In addition, a systematic literature search of studies published in 2003-2015 was performed to assess BRCA mutation frequency in population-based OC patients unselected for patient characteristics (personal history, family history, and Ashkenazi Jewish ethnicity) and to describe the association of patient characteristics with BRCA mutation. Exclusively, studies assessing epithelial OC or invasive epithelial OC with full gene screening of both BRCA1 and BRCA2 mutations were evaluated. RESULTS: Of 15 guidelines recommending genetic testing for OC patients, only 5 do not require co occurrence of specific patient or family characteristics. Twenty-two full publications were identified that assessed germline BRCA mutation frequency in women with OC, utilizing a range of different full mutation detection methods. Germline BRCA mutation prevalence in patients with OC was 5.8-24.8%. Using criteria recommended in guidelines that are yet to be updated, we estimated that 27.5% of all germline BRCA mutations present in patients with OC may be missed because patients do not meet appropriate criteria. CONCLUSION: With the availability of BRCA mutation-targeted therapies, identification of patients with OC with germline BRCA mutations has potential therapeutic consequences. For identified gene carriers, predictive testing to allow cancer prevention strategies, including bilateral salpingo-oophorectomy, provides wider benefit to identifying such gene carriers. Updating guidelines will increase the opportunity for targeted treatment among patients and risk reduction in relatives. FUNDING: AstraZeneca. PMID- 26809253 TI - Comparison of the Efficacy and Safety of Insulin Detemir and Insulin Glargine in Hospitalized Patients with Type 2 Diabetes: A Randomized Crossover Trial. AB - INTRODUCTION: Previous studies comparing insulin detemir versus insulin glargine showed conflicting results, and included only outpatients. This study compared the two insulin analogs once daily in hospitalized patients with type 2 diabetes (T2D). METHODS: A total of 55 patients aged 18-80 years with hyperglycemia admitted to the endocrinology wards were screened between June 2014 and February 2015. Forty-two enrolled patients were randomly assigned to receive either insulin detemir followed by insulin glargine once daily (n = 21), or vice versa (n = 21). The two insulin analogs were titrated 0.1 U/kg once daily based on fasting blood glucose (FBG). After achieving FBG <7.8 mmol/L (the first period), subjects were switched from one analog to the other (the second period) with no change in the dose. The second period lasted for 3 days. When hypoglycemia occurred in the second period, the observation was discontinued. Six-point blood glucose including FBG, 2 h after breakfast, lunch, dinner, bedtime, and at 3:00 am was tested every day. The glucose profiles of the final days in the two periods were compared. RESULTS: At the end of the first period, days for achieving FBG target (4.0 +/- 0.5 days vs. 3.3 +/- 0.4 days, t = 1.079, P = 0.286) and total daily dose (30.1 +/- 2.4 U vs. 30.1 +/- 2.9 U, t = 0.002, P = 0.999) between insulin detemir and insulin glargine were similar. There was no significant difference in the 24-h glucose control between the two analogs. No hypoglycemia occurred with both analogs in the first period. However, in the second period, when insulin glargine was switched to insulin detemir, two, three and, one patients had hypoglycemia events on day 1, day 2 and day 3 of the second period, respectively. One patient had severe hypoglycemia on day 1. CONCLUSION: When both basal insulin analogs were given once daily in T2D, insulin detemir achieved similar efficacy to insulin glargine. On the other hand, there may be differences in action of the compared basal insulins. Further studies with larger patient samples are necessary to support evidence and reveal possible mechanisms. PMID- 26809251 TI - 25 Years of Contrast-Enhanced MRI: Developments, Current Challenges and Future Perspectives. AB - In 1988, the first contrast agent specifically designed for magnetic resonance imaging (MRI), gadopentetate dimeglumine (Magnevist((r))), became available for clinical use. Since then, a plethora of studies have investigated the potential of MRI contrast agents for diagnostic imaging across the body, including the central nervous system, heart and circulation, breast, lungs, the gastrointestinal, genitourinary, musculoskeletal and lymphatic systems, and even the skin. Today, after 25 years of contrast-enhanced (CE-) MRI in clinical practice, the utility of this diagnostic imaging modality has expanded beyond initial expectations to become an essential tool for disease diagnosis and management worldwide. CE-MRI continues to evolve, with new techniques, advanced technologies, and novel contrast agents bringing exciting opportunities for more sensitive, targeted imaging and improved patient management, along with associated clinical challenges. This review aims to provide an overview on the history of MRI and contrast media development, to highlight certain key advances in the clinical development of CE-MRI, to outline current technical trends and clinical challenges, and to suggest some important future perspectives. FUNDING: Bayer HealthCare. PMID- 26809254 TI - Cross-species transmission of CWD prions. AB - Prions cause fatal neurodegenerative diseases in humans and animals and can be transmitted zoonotically. Chronic wasting disease (CWD) is a highly transmissible prion disease of wild deer and elk that affects cervids over extensive regions of the United States and Canada. The risk of cross-species CWD transmission has been experimentally evaluated in a wide array of mammals, including non-human primates and mouse models expressing human cellular prion protein. Here we review the determinants of cross-species CWD transmission, and propose a model that may explain a structural barrier for CWD transmission to humans. PMID- 26809257 TI - Cluster randomised-control trial for an Australian child protection education program: Study protocol for the Learn to be safe with Emmy and friendsTM. AB - BACKGROUND: Child maltreatment has severe short-and long-term consequences for children's health, development, and wellbeing. Despite the provision of child protection education programs in many countries, few have been rigorously evaluated to determine their effectiveness. We describe the design of a multi site gold standard evaluation of an Australian school-based child protection education program. The intervention has been developed by a not-for-profit agency and comprises 5 1-h sessions delivered to first grade students (aged 5-6 years) in their regular classrooms. It incorporates common attributes of effective programs identified in the literature, and aligns with the Australian education curriculum. METHODS/DESIGN: A three-site cluster randomised controlled trial (RCT) of Learn to be safe with Emmy and friendsTM will be conducted with children in approximately 72 first grade classrooms in 24 Queensland primary (elementary) schools from three state regions, over a period of 2 years. Entire schools will be randomised, using a computer generated list of random numbers, to intervention and wait-list control conditions, to prevent contamination effects across students and classes. Data will be collected at baseline (pre-assessment), immediately after the intervention (post-assessment), and at 6-, 12-, and 18 months (follow-up assessments). Outcome assessors will be blinded to group membership. Primary outcomes assessed are children's knowledge of program concepts; intentions to use program knowledge, skills, and help-seeking strategies; actual use of program material in a simulated situation; and anxiety arising from program participation. Secondary outcomes include a parent discussion monitor, parent observations of their children's use of program materials, satisfaction with the program, and parental stress. A process evaluation will be conducted concurrently to assess program performance. DISCUSSION: This RCT addresses shortcomings in previous studies and methodologically extends research in this area by randomising at school-level to prevent cross-learning between conditions; providing longer-term outcome assessment than any previous study; examining the degree to which parents/guardians discuss intervention content with children at home; assessing potential moderating/mediating effects of family and child demographic variables; testing an in-vivo measure to assess children's ability to discriminate safe/unsafe situations and disclose to trusted adults; and testing enhancements to existing measures to establish greater internal consistency. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Register (ACTRN12615000917538). Registered (02/09/2015). PMID- 26809258 TI - Erratum to: Prescribed therapy for asthma: therapeutic ratios and outcomes. PMID- 26809259 TI - Does revision ACL reconstruction measure up to primary surgery? A meta-analysis comparing patient-reported and clinician-reported outcomes, and radiographic results. AB - PURPOSE: To compare patient-reported and clinician-reported outcomes, and radiographic results between patients who had had revision ACL reconstruction and those who had had primary ACL reconstruction. DESIGN: Systematic review and meta analysis DATA SOURCES: The MEDLINE, CINAHL, EMBASE and SPORTDiscus electronic databases were searched on 6 August 2015, using 3 main concepts: (1) revision ACL reconstruction, (2) primary ACL reconstruction and (3) treatment outcomes. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Articles that compared patient reported or clinician-reported outcomes or radiographic results between patients who had had revision ACL reconstruction and those who had had primary surgery with a minimum of 2 years follow-up were included. The outcomes evaluated were the Lysholm Knee Scoring Scale, objective International Knee Documentation Committee (IKDC) classification, Tegner Activity Scale, side-to-side difference in anterior tibial translation measured with KT-1000/2000 arthrometer, pivot shift test, tibiofemoral osteoarthritis grading on plain radiographs and subsequent knee surgeries. RESULTS: 8 studies (300 revision ACL reconstructions and 413 primary ACL reconstructions) were included in the meta-analysis. Patients who had had revision surgery reported inferior Lysholm Knee Scoring Scale scores (mean difference: 7.8 points), had inferior clinician-reported knee function as assessed with the objective IKDC classification (IKDC category A: 27% vs 57%; IKDC category C or D: 22% vs 8%) and pivot shift test (grade II or III: 7% vs 2%), and more radiographic evidence of tibiofemoral osteoarthritis (50% vs 25%) compared with patients who had had primary surgery. CONCLUSIONS: Revision ACL reconstruction restored similar anterior-posterior knee laxity compared with primary ACL reconstruction. Patients who had had revision surgery reported inferior Lysholm Knee Scoring Scale scores, had inferior clinician-reported knee function and more radiographic signs of tibiofemoral osteoarthritis compared with patients with primary ACL reconstruction. PMID- 26809260 TI - Cognition enhancing drugs ('nootropics'): time to include coaches and team executives in doping tests? PMID- 26809261 TI - High resolution MRI in treatment decision of anterior communicating artery aneurysm accompanied by visual symptoms: Endovascular treatment or surgical clipping? A report of two cases and literature review. AB - Anterior communicating artery (AComA) aneurysm accompanied by visual symptoms is rarely reported. The first case is an asymptomatic 65-year-old woman who presented with an AComA aneurysm, and the pre-procedure high-resolution magnetic resonance imaging (MRI) revealed an AComA aneurysm compressed the left optic nerve and the chiasma with a size of 8.3 * 9.2 mm. She suffered a sudden onset of left eye visual loss and the temporal hemianopia of the right eye after endovascular embolization. She had a light sensation of the left eye and minor enlargement of the visual field in the right eye at the six-month follow-up. The second case is a symptomatic 55-year-old woman suffering a visual loss in the left eye and inferior nasal quadrantanopsia in her right eye. Pre-operative high resolution MRI found an AComA aneurysm compressing the left part of the chiasma with a size of 7.1 * 8.3 mm. Her visual symptoms improved after surgical clipping. High-resolution MRI could depict the anatomic relationship between the AComA aneurysm and the surrounding optic pathways. Endovascular treatment of an AComA aneurysm may result in visual deterioration due to the mass effect or ischemia after the procedure. Surgical clipping of the AComA aneurysm could relieve the compression symptoms. PMID- 26809262 TI - T-bet expression in CD8+ T cells associated with chronic hepatitis B virus infection. AB - BACKGROUND: The mechanisms leading to virus-specific CD8+ T cell dysfuction in chronic hepatitis B virus (HBV) infection remain to be elucidated. Our study focused on the role of transcription factor T-bet in HBV infection because it is a crucial regulator of T cell immunity. METHODS: We assessed the expression of T bet along with PD-1, IFN-gamma and perforin, in HBV-specific CD8+ T cells from resolved acute hepatitis B (rAHB) patients, chronic hepatitis B (CHB) patients, as well as asymptomatic HBV carriers (ASCs). We observed dynamic changes of T bet, PD-1, IFN-gamma and perforin in acute stage and recovery stage of acute hepatitis B (AHB). RESULTS: Comparing with other cohorts, HBV-specific CD8+ T cells from rAHB demonstrated a superior ability in T-bet, IFN-gamma and perforin expression, but an inferior ability in PD-1 expression. In the CHB group, the level of T-bet has a linear relationship with the level of PD-1, IFN-gamma and HBV DNA, respectively. A lower expression of T-bet and PD-1 was observed in ASCs when compared with CHB. A higher expression of T-bet, PD-1, IFN-r and perforin was observed in acute stage when compared with the recovery stage of AHB. CONCLUSIONS: Our results suggest that expression of T-bet may influence the function of HBV-specific CD8+ T cells and thus can be an attractive target for modulation to improve HBV-specific immunity in CHB. PMID- 26809264 TI - Influence of Dual-Bt Protein Corn on Bollworm, Helicoverpa zea (Boddie), Survivorship on Bollgard II Cotton. AB - Similar Cry proteins are expressed in both Bt corn, Zea mays L., and cotton, Gossypium hirsutum (L.), commercial production systems. At least one generation of corn earworm, Helicoverpa zea (Boddie), completes development on field corn in the Mid-South before dispersing across the landscape into other crop hosts like cotton. A concern is that Bt corn hybrids may result in selection for H. zea populations with a higher probability of causing damage to Bt cotton. The objective of this study was to determine the susceptibility of H. zea offspring from moths that developed on non-Bt and VT Triple Pro (VT3 PRO) field corn to lyophilized Bollgard II cotton tissue expressing Cry1Ac and Cry2Ab. Offspring of individuals reared on VT3 PRO expressing Cry1A.105 and Cry2Ab had a significantly higher LC50 two out of the three years this study was conducted. Excess larvae were placed on artificial diet and allowed to pupate to determine if there were any inheritable fitness costs associated with parental development on VT3 PRO corn. Offspring resulting from males collected from VT3 PRO had significantly lower pupal weight and longer pupal duration compared with offspring of individuals collected from non-Bt corn. However, offspring from females collected from VT3 PRO were not different from non-Bt offspring. Paternal influence on offspring in insects is not commonly observed, but illustrates the side effects of development on a transgenic plant expressing less than a high dose, 25 times the concentration needed to kill susceptible larvae. PMID- 26809263 TI - Novel insights into the effect of vitamin B12 and omega-3 fatty acids on brain function. AB - The prevalence of psychiatric disorders which are characterized by cognitive decline is increasing at an alarming rate and account for a significant proportion of the global disease burden. Evidences from human and animal studies indicate that neurocognitive development is influenced by various environmental factors including nutrition. It has been established that nutrition affects the brain throughout life. However, the mechanisms through which nutrition modulates mental health are still not well understood. It has been suggested that the deficiencies of both vitamin B12 and omega-3 fatty acids can have adverse effects on cognition and synaptic plasticity. Studies indicate a need for supplementation of vitamin B12 and omega-3 fatty acids to reduce the risk of cognitive decline, although the results of intervention trials using these nutrients in isolation are inconclusive. In the present article, we provide an overview of vitamin B12 and omega-3 fatty acids, the possible mechanisms and the evidences through which vitamin B12 and omega-3 fatty acids modulate mental health and cognition. Understanding the role of vitamin B12 and omega-3 fatty acids on brain functioning may provide important clues to prevent early cognitive deficits and later neurobehavioral disorders. PMID- 26809266 TI - Predicting outcome in 259 fetuses with agenesis of ductus venosus - a multicenter experience and systematic review of the literature (.). AB - OBJECTIVE: To evaluate prenatal predictors of postnatal survival in fetuses with agenesis of ductus venosus (ADV). METHODS: This retrospective study reviewed our experience and the literature between 1991 and 2015. Prenatal findings were evaluated and perinatal morbidity and mortality was documented. RESULTS: A total of 259 cases were included in the present analysis from our centers and 49 published studies (15 patients from our retrospective cohort review and 244 from literature review). The intrahepatic and extrahepatic shunts were present in 32.0% (73/226) and 67.7% (153/226), respectively. Cardiomegaly (n = 64/259, 24.7%), hydrops (n = 31/259, 12.0%) and amniotic fluid abnormalities (n = 22/259, 8.5%) were among the most frequent initial ultrasound findings. One hundred and forty-seven fetuses (56.8%) had ADV without structural anomalies while 112 (43.2%) had associated anomalies (cardiac anomalies (n = 66), extra-cardiac anomalies (n = 19) and both cardiac and extra-cardiac anomalies (n = 27)). The mean gestational age (GA) at ultrasound diagnosis was 22.9 +/- 6.9 weeks while the mean GA at delivery was 34 +/- 7.5 weeks. The overall neonatal survival was 57.1% (n = 148/259). The following factors were associated with survival: advanced maternal age, earlier GA at diagnosis, prematurity, increased nuchal translucency, pericardial effusion, associated cardiac defects (especially AVSD), chromosomal abnormalities, hydrops, hygroma and limb anomalies. CONCLUSION: Fetal hydrops, the presence of associated congenital anomalies and premature delivery are associated with poor prognosis in fetuses with ADV. PMID- 26809267 TI - Paclitaxel and Tacrolimus Coencapsulated Polymeric Micelles That Enhance the Therapeutic Effect of Drug-Resistant Ovarian Cancer. AB - The combination of chemotherapy drugs and multidrug-resistant reversing agents for treating multidrug resistance in tumors has attracted increasing attention. However, the poor water solubility of some anticancer drugs restricted their clinical application. In this work, we prepared poly(ethylene glycol) poly(epsilon-caprolactone) (MPEG-PCL) micelles as a codelivery system to load the chemotherapy drug paclitaxel (PTX) and the multidrug-resistant reversing agent tacrolimus (FK506). The PTX- and FK506-coloaded MPEG-PCL micelles (P-F/M) were prepared by a one-step solid dispersion method without any surfactants, toxic organic solvent, or severe experimental conditions. P-F/M had small particle size (28.7 +/- 3.2 nm) and high encapsulation efficiency (99.3 +/- 0.5%). Compared with A2780s cells (PTX-sensitive human ovarian cancer cells), P-F/M showed a stronger cytotoxicity and an improving intracellular drug concentration of PTX than PTX-loaded micelles (PTX/M) in A2780/T cells (PTX-resistant human ovarian cancer cells). Furthermore, a P-F/M codelivery system showed a more significant G2/M arrest and apoptosis induction effects, as well as activating apoptosis protein signaling pathway, in A2780/T cells than in A2780s cells. In summary, the results suggested that the codelivery micelles of PTX and FK506 may serve as a potential candidates against MDR human ovarian cancer. PMID- 26809270 TI - Iontophoretic transdermal fentanyl for the management of acute perioperative pain in hospitalized patients. AB - INTRODUCTION: Intravenous (I.V.) morphine administered through a patient controlled system currently represents the gold standard treatment for moderate to severe acute postoperative pain. To fix the limitations showed by the available I.V. patient-controlled analgesia (PCA) systems that may restrict its use in the clinical practice a needle-free, iontophoretic, fentanyl patient controlled transdermal system has been developed and recently approved by the United States Food and Drug Administration (FDA) and by the European Medicines Agency (EMA). AREAS COVERED: This review aims at describing the technology, pharmacology and clinical efficacy of fentanyl iontophoretic transdermal system (ITS) in the treatment of acute pain. A literature search was conducted in the PUBMED database using the term 'fentanyl iontophoretic transdermal system' through September 2015 and results from the main clinical trials are discussed. EXPERT OPINION: In 2015, the appropriate treatment of acute pain after surgery is still a challenge and it represents a primary goal in the care of the surgical patient. When regional analgesia techniques are not applicable and systemic analgesia is required, patient controlled systems represent the standard of care for opioid administration. The fentanyl ITS presents several potential advantages compared to the currently used PCA devices. In particular, it does not require intravenous lines and eliminates the potential for drug administration errors, observed with manually programmed standard PCA devices. Nevertheless, further studies are needed to address eventual inter-individual variability especially for opioid tolerant patients. PMID- 26809268 TI - Converging effects of cocaine addiction and sex on neural responses to monetary rewards. AB - There is some evidence that cocaine addiction manifests as more severe in women than men. Here, we examined whether these sex-specific differences in the clinical setting parallel differential neurobehavioral sensitivity to rewards in the laboratory setting. Twenty-eight (14 females/14 males) cocaine-dependent and 25 (11 females/14 males) healthy individuals completed a monetary reward task during fMRI. Results showed that the effects of cocaine dependence and sex overlapped in regions traditionally considered part of the mesocorticolimbic brain circuits including the hippocampus and posterior cingulate cortex (PCC), as well as those outside of this circuit (e.g., the middle temporal gyrus). The nature of this 'overlap' was such that both illness and female sex were associated with lower activations in these regions in response to money. Diagnosis-by-sex interactions instead emerged in the frontal cortex, such that cocaine-dependent females exhibited lower precentral gyrus and greater inferior frontal gyrus (IFG) activations relative to cocaine-dependent males and healthy females. Within these regions modulated both by diagnosis and sex, lower activation in the hippocampus and PCC, and higher IFG activations, correlated with increased subjective craving during the task. Results suggest sex-specific differences in addiction extend to monetary rewards and may contribute to core symptoms linked to relapse. PMID- 26809272 TI - Combination bupropion SR and varenicline for smoking cessation: a systematic review. AB - BACKGROUND: Tobacco is the leading cause of preventable death in the world. Current cessation medications include nicotine replacement therapy (NRT), varenicline, and bupropion, while combination therapy primarily entails NRT with either varenicline or bupropion. However, recent studies have examined varenicline and bupropion in combination. OBJECTIVES: A systematic review assessing the efficacy and safety of combination varenicline and bupropion was conducted. METHODS: PubMed and Clinicaltrials.gov were searched using terms: "varenicline combination", "bupropion combination", "bupropion AND varenicline", and "bupropion AND varenicline combination smoking cessation", yielding four studies including 1193 total patients. RESULTS: Combination therapy yielded greater efficacy than varenicline monotherapy in two randomized controlled trials and one retrospective outcomes study. One single-arm Phase II trial provided additional efficacy and safety data. Of the prospective trials, one displayed a greater 4-week smoking abstinence for weeks 8-11 with combination (39.8%) versus monotherapy (25.9%) (OR = 1.89; 95% CI = 1.07-3.35). The other demonstrated greater prolonged abstinence (continuous abstinence from week 2) at 12 weeks (OR = 1.49; 95% CI = 1.05-2.12) and 26 weeks (OR = 1.52; 95% CI = 1.04-2.22), though results were not significant at 52 weeks in this study. The retrospective study displayed higher success rates (continuous abstinence rates at 52 weeks) with combination varenicline and bupropion (55.0%; compared to varenicline monotherapy (32.1%), p < 0.001). Subgroup analyses suggest that this combination may be more beneficial in males and patients with higher baseline nicotine dependence. CONCLUSION: To the authors' knowledge, this is the first review conducted to compile current literature on this novel pharmacotherapy combination for smoking cessation. Combination bupropion SR and varenicline displayed greater efficacy in smoking cessation than varenicline monotherapy, though further safety analysis is warranted to rule out additive psychiatric adverse effects. PMID- 26809275 TI - Circulating 25-Hydroxyvitamin D and Prostate Cancer Survival. AB - BACKGROUND: Recent epidemiologic evidence suggests that higher circulating vitamin D does not protect against prostate cancer and, in fact, may increase the risk of developing this malignancy. However, few studies have examined the most clinically relevant outcome, prostate cancer mortality. METHODS: We examined prediagnostic serum 25-hydroxy-vitamin D (25(OH)D) and prostate cancer survival in a cohort of 1,000 cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. During 23 years of follow-up, 363 men died from their disease. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of death from prostate cancer by season specific quintile of 25(OH)D. Multivariable models were adjusted for age, physical activity, cigarettes per day, and family history of prostate cancer. RESULTS: Men with higher serum 25(OH)D were less likely to die from their prostate cancer (Q5 vs. Q1 HR, 0.72; 95% CI, 0.52-0.99; Ptrend = 0.006). This finding was independent of stage or grade at diagnosis and appeared restricted to men who survived longer (survived <3.3 years: Q5 vs. Q1 HR, 0.95; 95% CI, 0.61 1.50; Ptrend, 0.53; survived >=3.3 years: Q5 vs. Q1 HR, 0.53; 95% CI, 0.34-0.85; Ptrend, 0.0002). CONCLUSIONS: In this population of men diagnosed with prostate cancer, higher serum 25(OH)D years prior to diagnosis was associated with longer prostate cancer survival. IMPACT: In light of inconsistent evidence regarding the role of vitamin D in the development of prostate cancer, the present findings regarding the most clinically relevant prostate cancer outcome, disease-specific mortality, could have important public health implications. Cancer Epidemiol Biomarkers Prev; 25(4); 665-9. (c)2016 AACR. PMID- 26809274 TI - Germline Genetic Variants in the Wnt/beta-Catenin Pathway as Predictors of Colorectal Cancer Risk. AB - BACKGROUND: The Wnt/beta-catenin signaling pathway plays a key role in stem cell maintenance in the colorectum. Rare high-penetrance genetic mutations in components of this pathway result in familial colorectal cancer, yet the impact of common, germline variants remains unknown. METHODS: We assessed 172 variants in 26 genes from the Wnt/beta-catenin pathway in 809 colorectal cancer cases and 814 healthy controls, followed by replication of the top findings in another 691 cases and 775 controls. In silico informatic tools were used to predict functional effects of variants. RESULTS: Eighteen SNPs in the pathway were significantly associated with colorectal cancer risk (P < 0.05) in the discovery phase. We observed a significant dose-response increase in colorectal cancer risk by number of risk genotypes carried (P = 4.19 * 10(-8)). Gene-based analysis implicated CSNK1D (P = 0.014), FZD3 (P = 0.023), and APC (P = 0.027) as significant for colorectal cancer risk. In the replication phase, FZD3:rs11775139 remained significantly associated with reduced risk with a pooled OR of 0.85 [95% confidence interval (CI), 0.76-0.94, P = 0.001]. Although borderline significant in the replication population, APC:rs2545162 was highly significant in the pooled analysis-OR, 1.42; 95% CI, 1.16-1.74; P = 0.00085. Functional assessment identified several potential biologic mechanisms underlying these associations. CONCLUSIONS: Our findings suggest that common germline variants in the Wnt/beta catenin pathway may be involved in colorectal cancer development. IMPACT: These variants may be informative in colorectal cancer risk assessment to identify individuals at increased risk who would be candidates for screening. PMID- 26809276 TI - Racial Differences in the Association Between Preoperative Serum Cholesterol and Prostate Cancer Recurrence: Results from the SEARCH Database. AB - BACKGROUND: Black men are disproportionately affected by both cardiovascular disease and prostate cancer. Epidemiologic evidence linking dyslipidemia, an established cardiovascular risk factor, and prostate cancer progression is mixed. As existing studies were conducted in predominantly non-black populations, research on black men is lacking. METHODS: We identified 628 black and 1,020 non black men who underwent radical prostatectomy and never used statins before surgery in the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Median follow-up was 2.9 years. The impact of preoperative hypercholesterolemia on risk of biochemical recurrence was examined using multivariable, race stratified proportional hazards. In secondary analysis, we examined associations with low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides, overall and among men with dyslipidemia. RESULTS: High cholesterol was associated with increased risk of recurrence in black [HR(per10 mg/dL) 1.06; 95% confidence interval (CI), 1.02-1.11] but not non-black men (HR(per10 mg/dL) 0.99; 95% CI, 0.95-1.03; P(interaction) = 0.011). Elevated triglycerides were associated with increased risk in both black and non-black men (HR(per10 mg/dL) 1.02; 95% CI, 1.00-1.03 and 1.02; 95% CI, 1.00-1.02, respectively; P(interaction) = 0.458). There were no significant associations between LDL or HDL and recurrence risk in either race. Associations with cholesterol, LDL, and triglycerides were similar among men with dyslipidemia, but low HDL was associated with increased risk of recurrence in black, but not non-black men with dyslipidemia (P(interaction) = 0.047). CONCLUSION: Elevated cholesterol was a risk factor for recurrence in black but not non-black men, whereas high triglycerides were associated with increased risk regardless of race. IMPACT: Significantly contrasting associations by race may provide insight into prostate cancer racial disparities. PMID- 26809277 TI - Raw Garlic Consumption and Lung Cancer in a Chinese Population. AB - BACKGROUND: Evidence of anticancer properties of garlic for different cancer sites has been reported previously in in vitro and in vivo experimental studies but there is limited epidemiologic evidence on the association between garlic and lung cancer. METHODS: We examined the association between raw garlic consumption and lung cancer in a case-control study conducted between 2005 and 2007 in Taiyuan, China. Epidemiologic data was collected by face-to-face interviews from 399 incident lung cancer cases and 466 healthy controls. We used unconditional logistic regression models to estimate crude and adjusted ORs (aOR) and their 95% confidence intervals (CI). Adjusted models controlled for age, sex, average annual household income 10 years ago, smoking, and indoor air pollution. RESULTS: Compared with no intake, raw garlic intake was associated with lower risk of development of lung cancer with a dose-response pattern (aOR for <2 times/week = 0.56; 95% CI, 0.39-0.81 and aOR for >=2 times/week = 0.50; 95% CI, 0.34-0.74; Ptrend = 0.0002). Exploratory analysis showed an additive interaction of raw garlic consumption with indoor air pollution and with any supplement use in association with lung cancer. CONCLUSIONS: The results of the current study suggest that raw garlic consumption is associated with reduced risk of lung cancer in a Chinese population. IMPACT: This study contributes to the limited research in human population on the association between garlic and lung cancer and advocates further investigation into the use of garlic in chemoprevention of lung cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 624-33. (c)2016 AACR. PMID- 26809279 TI - Amygdala activity during autobiographical memory recall as a biomarker for residual symptoms in patients remitted from depression. AB - We performed a linear regression analysis on demographic, memory performance, and amygdala activity during memory recall on 23 unmedicated participants remitted from major depressive disorder. Amygdala activity during positive memory recall, and the percent of specific positive memories recalled were the variables that explained the most variance in residual depressive symptoms. This model was not significant in control or currently depressed participants. Longitudinal follow up is necessary to assess whether these variables predict relapse. PMID- 26809280 TI - Classification of thermophilic actinobacteria isolated from arid desert soils, including the description of Amycolatopsis deserti sp. nov. AB - The taxonomic position of 26 filamentous actinobacteria isolated from a hyper arid Atacama Desert soil and 2 from an arid Australian composite soil was established using a polyphasic approach. All of the isolates gave the diagnostic amplification product using 16S rRNA oligonucleotide primers specific for the genus Amycolatopsis. Representative isolates had chemotaxonomic and morphological properties typical of members of the genus Amycolatopsis. 16S rRNA gene analyses showed that all of the isolates belong to the Amycolatopsis methanolica 16S rRNA gene clade. The Atacama Desert isolates were assigned to one or other of two recognised species, namely Amycolatopsis ruanii and Amycolatopsis thermalba, based on 16S rRNA gene sequence, DNA:DNA relatedness and phenotypic data; emended descriptions are given for these species. In contrast, the two strains from the arid Australian composite soil, isolates GY024(T) and GY142, formed a distinct branch at the periphery of the A. methanolica 16S rRNA phyletic line, a taxon that was supported by all of the tree-making algorithms and by a 100 % bootstrap value. These strains shared a high degree of DNA:DNA relatedness and have many phenotypic properties in common, some of which distinguished them from all of the constituent species classified in the A. methanolica 16S rRNA clade. Isolates GY024(T) and GY142 merit recognition as a new species within the A. methanolica group of thermophilic strains. The name proposed for the new species is Amycolatopsis deserti sp. nov.; the type strain is GY024(T) (=NCIMB 14972(T) = NRRL B-65266(T)). PMID- 26809281 TI - Hymenobacter rubidus sp. nov., bacterium isolated from a soil. AB - Strain DG7B(T) was isolated from a soil sample collected in Seoul, Republic of Korea and was observed to be a gram-negative, short-rod shaped and non-motile bacterium. Its 16S rRNA gene sequence is closely related to those of Hymenobacter terrae DG7A(T) (97.8 % similarity), H. soli PB17(T) (97.5 %), H. glaciei VUG A130(T) (96.4 %), H. saemangeumensis GSR0100(T) (95.7 %), H. ruber PB156(T) (95.3 %), and H. antarcticus VUG-A42aa(T) (95.3 %). The low levels of DNA-DNA relatedness (<50.3 %) with the above species identified strain DG7B(T) as a novel species in the genus Hymenobacter. The genomic DNA G+C content was determined to be 54.9 %. Growth of strain DG7B(T) was observed at 12-30 degrees C (optimum at 25 degrees C) and pH 6.0-11.0 (optimum at pH 7). The cells tolerate <0.5 % NaCl. A UV-visible scan of an ethanol extract of the whole cell pigment showed absorbance peaks at 264.5, 320.0, and 481.5 nm, so the pigment type was determined to be 2'-hydroxyflexixanthin. Chemotaxonomic data showed that strain DG7B(T) possesses menaquinone-7 as the predominant isoprenoid quinone, sym homospermidine as the major polyamine, phosphatidylethanolamine as the predominant polar lipid and iso-C15:0, anteiso-C15:0 and summed feature 3 (C16:1 omega7c/C16:1 omega7c) as the major fatty acids. Strain DG7B(T) showed low-level resistance to ultraviolet C. Based on the polyphasic analysis, it is concluded that strain DG7B(T) (=KCTC 32553(T) = KEMB 9004-166(T) = JCM 30008(T)) should be classified as the type strain of a novel Hymenobacter species, for which the name Hymenobacter rubidus sp. nov. is proposed. PMID- 26809278 TI - Mouse models for gastric cancer: Matching models to biological questions. AB - Gastric cancer is the third leading cause of cancer-related mortality worldwide. This is in part due to the asymptomatic nature of the disease, which often results in late-stage diagnosis, at which point there are limited treatment options. Even when treated successfully, gastric cancer patients have a high risk of tumor recurrence and acquired drug resistance. It is vital to gain a better understanding of the molecular mechanisms underlying gastric cancer pathogenesis to facilitate the design of new-targeted therapies that may improve patient survival. A number of chemically and genetically engineered mouse models of gastric cancer have provided significant insight into the contribution of genetic and environmental factors to disease onset and progression. This review outlines the strengths and limitations of current mouse models of gastric cancer and their relevance to the pre-clinical development of new therapeutics. PMID- 26809283 TI - Differential effects of salinity and osmotic stress on the plant growth-promoting bacterium Gluconacetobacter diazotrophicus PAL5. AB - Plant growth-promoting bacteria (PGPB) represent a promising alternative to the massive use of industrial fertilizers in agriculture. Gluconacetobacter diazotrophicus is a PGPB that colonizes several plant species. Although this bacterium is able to grow at high sucrose concentrations, its response to environmental stresses is poorly understood. The present study evaluated G. diazotrophicus PAL5 response to stresses caused by sucrose, PEG 400, NaCl, KCl, Na2SO4 and K2SO4. Morphological, ultrastructural and cell growth analysis revealed that G. diazotrophicus PAL5 is more sensitive to salt than osmotic stress. Growth inhibition and strong morphological changes were caused by salinity, in consequence of Cl ion-specific toxic effect. Interestingly, low osmotic stress levels were beneficial for bacterial multiplication, which was able to tolerate high sucrose concentrations, Na2SO4 and K2SO4. Our data show that G. diazotrophicus PAL5 has differential response to osmotic and salinity stress, which may influence its use as inoculant in saline environments. PMID- 26809284 TI - Automated Multiplug Filtration Cleanup for Pesticide Residue Analyses in Kiwi Fruit (Actinidia chinensis) and Kiwi Juice by Gas Chromatography-Mass Spectrometry. AB - To reduce labor-consuming manual operation workload in the cleanup steps, an automated multiplug filtration cleanup (m-PFC) method for QuEChERS (quick, easy, cheap, effective, rugged, and safe) extracts was developed. It could control the volume and speed of pulling and pushing cycles accurately. In this study, m-PFC was based on multiwalled carbon nanotubes (MWCNTs) mixed with primary-secondary amines (PSA) and anhydrous magnesium sulfate (MgSO4) in a packed column for analysis of pesticide residues followed by gas chromatography-mass spectrometry (GC-MS) detection. It was validated by analyzing 33 pesticides in kiwi fruit and kiwi juice matrices spiked at two concentration levels of 10 and 100 MUg/kg. Salts, sorbents, m-PFC procedure, 4 mL of automated pulling and pushing volume, 6 mL/min automated pulling speed, and 8 mL/min pushing speed were optimized for each matrix. After optimization, spike recoveries were within 71-120% and <20% RSD for all analytes in kiwi fruit and kiwi juice. Matrix-matched calibrations were performed with the coefficients of determination >0.99 between concentration levels of 10 and 1000 MUg/kg. The developed method was successfully applied to the determination of pesticide residues in market samples. PMID- 26809285 TI - BCG vaccine for immunotherapy in warts: is it really safe in a tuberculosis endemic area? AB - Management of recurrent and or recalcitrant warts can be a therapeutic challenge and in such cases invoking body's own immunity may help to overcome the present episode and also prevent recurrences. Bacilli Calmette Geurin (BCG) immunotherapy has long been considered to be an effective and safe modality in such cases. We present a series of seven cases treated with BCG immunotherapy wherein a single dose of BCG caused regression of wart in 85.7% patients and complete resolution was evident in 28.6% patients. However, the development of adverse effects precluded any further dosages in four of seven (57.1%) patients. This raises serious concern on the safety of this therapeutic modality, especially in a population endemic to tuberculosis. PMID- 26809286 TI - Neuronal Hemoglobin Expression and Its Relevance to Multiple Sclerosis Neuropathology. AB - Multiple sclerosis (MS) is characterized by demyelination and progressive neurological disability. Previous studies have reported defects to mitochondria in MS including decreased expression of nuclear encoded electron transport chain subunit genes and inhibition of respiratory complexes. We previously reported increased levels of the hemoglobin beta subunit (Hbb) in mitochondrial fractions isolated from postmortem MS cortex compared to controls. In the present study, we performed immunohistochemistry to determine the distribution of Hbb in postmortem MS cortex and identified proteins which interact with Hbb by liquid chromatography tandem mass spectrometry (LC-MS/MS). We found that Hbb was enriched in pyramidal neurons in internal layers of the cortex and interacts with subunits of ATP synthase, histones, and a histone lysine demethylase. We also found that Hbb is present in the nucleus and that expression of Hbb in SH-SY5Y neuroblastoma cells increased trimethylation of histone H3 on lysine 4 (H3K4me3), a histone mark that regulates cellular metabolism. These data suggest that Hbb may be a part of a mechanism linking neuronal energetics with epigenetic changes to histones in the nucleus and may provide neuroprotection in MS by supporting neuronal metabolism. PMID- 26809288 TI - Neural foundation of human moral reasoning: an ALE meta-analysis about the role of personal perspective. AB - Moral sense is defined as a feeling of the rightness or wrongness of an action that knowingly causes harm to people other than the agent. The large amount of data collected over the past decade allows drawing some definite conclusions about the neurobiological foundations of moral reasoning as well as a systematic investigation of methodological variables during fMRI studies. Here, we verified the existence of converging and consistent evidence in the current literature by means of a meta-analysis of fMRI studies of moral reasoning, using activation likelihood estimation meta-analysis. We also tested for a possible neural segregation as function of the perspective used during moral reasoning i.e., first or third person perspectives. Results demonstrate the existence of a wide network of areas underpinning moral reasoning, including orbitofrontal cortex, insula, amygdala, anterior cingulate cortex as well as precuneus and posterior cingulate cortex. Within this network we found a neural segregation as a function of the personal perspective, with 1PP eliciting higher activation in the bilateral insula and superior temporal gyrus as well as in the anterior cingulate cortex, lingual and fusiform gyri, middle temporal gyrus and precentral gyrus in the left hemisphere, and 3PP eliciting higher activation in the bilateral amygdala, the posterior cingulate cortex, insula and supramarginal gyrus in the left hemisphere as well as the medial and ventromedial prefrontal cortex in the right hemisphere. These results shed some more light on the contribution of these areas to moral reasoning, strongly supporting a functional specialization as a function of the perspective used during moral reasoning. PMID- 26809287 TI - Neural correlates of emotion reappraisal in individuals with externalizing psychopathology. AB - Externalizing psychopathology (EXT) is characterized by regulatory deficits of behavior, cognition, and negative emotion. Previous research on EXT suggests that cognitive and affective dysregulation are highly related, such that strong affective states constrain a reduced-capacity cognitive system. Reappraisal is an effective emotional control strategy involving complex interactions between cognitive and affective brain functions and may therefore offer novel insight into the specific neural mechanisms of affective dysregulation among individuals with EXT. To evaluate these possibilities, we tested individuals with low or high EXT in a reappraisal paradigm. Neuroimaging results indicated that EXT was associated with hypo-activation in the amygdala and superior parietal lobule during both maintenance and reappraisal as well as poor modulation of the lateral occipital cortex during negative emotion reappraisal. These results suggest a general disruption of perceptual-attentional resource allocation such that high EXT individuals are characterized by poor modulation of perceptual-attentional resources during reappraisal. Subsequently, emotion reappraisal may be a useful but not adequate tool to control negative affect in EXT. PMID- 26809289 TI - Cognitive dysfunction and symptom burden in women treated for breast cancer: a prospective behavioral and fMRI analysis. AB - Neural dysfunction and cognitive complaints are associated with chemotherapy for breast cancer although trajectory and contributory factors remain unclear. We prospectively examined neurocognition using fMRI and self-reported cognitive, physical and psychological symptoms in women treated with adjuvant chemotherapy over one year. Patients treated with (n = 28) or without (n = 34) chemotherapy for localized breast cancer and healthy controls (n = 30) performed a Verbal Working Memory Task (VWMT) during fMRI and provided self-reports at baseline (pre adjuvant treatment), five- (M5) and 12-months (M12). Repeated measures ANOVA and multivariable regression determined change over time and possible predictors (e.g., hemoglobin, physical symptoms, worry) of VWMT performance, fMRI activity in the frontoparietal executive network, and cognitive complaints at M12. Trajectories of change in VWMT performance for chemotherapy and healthy control groups differed significantly with the chemotherapy group performing worse at M12. Chemotherapy patients had persistently higher spatial variance (neural inefficiency) in executive network fMRI-activation than both other groups from baseline to M12. Cognitive complaints were similar among groups over time. At M12, VWMT performance and executive network spatial variance were each independently predicted by chemotherapy treatment and their respective baseline values, while cognitive complaints were predicted by baseline level, physical symptoms and worry. Executive network inefficiency and neurocognitive performance deficits pre-adjuvant treatment predict cognitive dysfunction one-year post baseline, particularly in chemotherapy-treated patients. Persistent cognitive complaints are linked with physical symptom severity and worry regardless of treatment. Pre-chemotherapy interventions should target both neurocognitive deficits and symptom burden to improve cognitive outcomes for breast cancer survivors. PMID- 26809292 TI - Left-sided cardiac chamber evaluation using single-phase mid-diastolic coronary computed tomography angiography: derivation of normal values and comparison with conventional end-diastolic and end-systolic phases. AB - OBJECTIVES: With increasing use of prospective scanning techniques for cardiac computed tomography (CT), meaningful evaluation of chamber volumes is no longer possible due to lack of normal values. We aimed to define normal values for mid diastolic (MD) chamber volumes and to determine their significance in comparison to maximum volumes. METHODS: Normal ranges at MD for left ventricular (LV) volume and mass and left atrial (LA) volume were determined from 101 normal controls. Thereafter, 109 consecutive CT scans, as well as 21 post-myocardial infarction patients, were analysed to determine the relationship between MD and maximum volumes. RESULTS: MD volumes correlated closely with maximal volumes (r = 0.99) for both LV and LA, and could estimate maximum volumes accurately. LV mass, measured at ED or MD, were very similar (r = 0.99). Abnormal MD volumes had excellent sensitivity and specificity to detect chamber enlargement based on maximal volumes (LV 86 %, 100 %, respectively; LA 100 %, 92 %, respectively). CONCLUSION: A single MD phase can identify patients with cardiomegaly or LV hypertrophy with a high degree of accuracy and MD volumes can give an accurate estimate of maximum LV and LA volumes. KEY POINTS: * Traditionally, helical cardiac CT provided clinically important information from chamber volume analysis. * Mid-diastolic left atrial and ventricular volumes correlate closely with maximal volumes. * We derive normal values for mid-diastolic left atrial and ventricular volumes and mass. * A single mid-diastolic phase can be used to identify chamber enlargement and hypertrophy. PMID- 26809297 TI - [The Main Target of Carcinogenesis Is Not DNA]. AB - The first target of radiation carcinogenesis is thought to be DNA. However, this has not been demonstrated for radiation carcinogenesis. We found that the frequency of aneuploid cells was closely related to that of radiation-induced cell transformation and natural cell transformation by high-density cultivation, but the frequency of gene mutations was not. Cells containing a functional p53 gene become tetraploid, but do not exhibit tumorigenicity. In contrast, cells without a functional p53 gene readily become triploid and acquire tumorigenicity. Both radiation exposure and high-density cultivation elevated the level of intracellular oxidative radicals. One of these radicals, such as long-lived radical, induced centrosome destabilization and produced cells carrying extra centrosomes, which together promote merotelic attachment of the chromosome by altering spindle geometry. Unresolved merotelic attachments can give rise to lagging chromosomes during anaphase. Aneuploidy was observed at high frequency in the early stages of cell transformation. These results strongly suggest that the main target in carcinogenesis induced by low-dose radiation is not DNA, but is rather the centrosomes, which are proteins involved in the chromosomal homeostasis maintenance mechanism. In addition, the route of radiation carcinogenesis may be the same as that of natural carcinogenesis. PMID- 26809293 TI - Feasibility of test-bolus DCE-MRI using CAIPIRINHA-VIBE for the evaluation of pancreatic malignancies. AB - OBJECTIVES: To evaluate the feasibility of test-bolus dynamic contrast-enhanced (DCE) MRI with CAIPIRINHA-VIBE for pancreatic malignancies. METHODS: Thirty-two patients underwent DCE-MRI with CAIPIRINHA-VIBE after injection of 2 mL gadolinium. From the resulting time-intensity curve (TIC), we estimated the arterial (AP) and portal venous phase (PVP) scan timing for subsequent multiphasic MRI. DCE-MRI perfusion maps were generated, and perfusion parameters were calculated. The image quality was rated on a 5-point scale (1: poor, 5: excellent). Goodness-of-fit of the TIC was evaluated by Pearson's chi2 test. RESULTS: Test-bolus DCE-MRIs with high temporal (3 s) and spatial resolution (1 * 1 * 4 mm3) were acquired with good-quality perfusion maps of Ktrans and iAUC (mean score 4.313 +/- 0.535 and 4.125 +/- 0.554, respectively). The mean chi2 values for fitted TICs were 0.115 +/- 0.082 for the pancreatic parenchyma and 0.784 +/- 0.074 for pancreatic malignancies, indicating an acceptable goodness-of fit. Test-bolus DCE-MRI was highly accurate in estimating the proper timing of AP (90.6 %) and PVP (100 %) of subsequent multiphasic MRI. Between pancreatic adenocarcinomas and neuroendocrine tumours, there were significant differences in the Ktrans (0.073 +/- 0.058 vs. 0.308 +/- 0.062, respectively; p = 0.007) and iAUC (1.501 +/- 0.828 vs. 3.378 +/- 0.378, respectively; p = 0.045). CONCLUSIONS: Test-bolus DCE-MRI using CAIPIRINHA-VIBE is feasible for incorporating perfusion analysis of pancreatic tumours into routine multiphasic MRI. KEY POINTS: * Test bolus DCE-MRI using CAIPIRINHA-VIBE is feasible for perfusion analysis of pancreatic tumours. * CAIPIRINHA-VIBE enables DCE-MRI with high temporal and spatial resolution. * Test-bolus DCE-MRI is highly accurate in estimating the proper timing of multiphasic MRI. PMID- 26809298 TI - [Kampo Therapy for Patients with Cancer--The Role of Kampo Medicine in Team Therapy]. AB - This study details the role of Kampo medicine in cancer therapy. Cancer normally cannot be cured only with Kampo medicine. Therefore, Kampo should be administered in combination with surgery, chemotherapy, or radiotherapy. In that context, Kampo is useful in team therapy for patients with cancer. One of the characteristics of Kampo medicine is that Kampo diagnosis does not target the disease, but the patient with the disease. Kampo diagnosis is called"pattern diagnosis". Many patients with cancer are diagnosed with a"deficiency pattern","cold pattern","qi deficiency pattern", or"blood deficiency pattern". Based on these diagnoses, hochuekkito or juzentaihoto are often used for patients with cancer. Many other Kampo formulae can be used for patients with cancer diagnosed with the"qi deficiency pattern"and/or"blood deficiency pattern". Kampo is not only considered an herbal therapy, but also acupuncture/moxibustion and Yojo (nourishing life). To implement these Kampo modalities comprehensively, team therapy is essential. In order to treat a patient with cancer, rather than the cancer itself, Kampo can be used effectively. PMID- 26809299 TI - [Symptoms of Cancer Patients and Kampo Formulas Effective for Them]. AB - Patients with cancer exhibit various symptoms induced by cancer itself and its therapy leadingto fatigue; however, their vital energy can be restored by administration of Kampo, which is a traditional Japanese herbal medicine. Restoration and maintenance of mental and physical energy are important for successful cancer treatment. For this purpose, appropriate use of Kampo formulas, such as"Ho-zai", formulas to vitalize fatigued patients (eg, Hochu-ekki-to, Juzen taiho-to, Ninjin-yoeito), "Hojin-zai", formulas to restore energy (eg, Gosha jinki-gan), and"Kuoketsu-zai ", formulas to resolve stagnant blood flow (eg, Keishi-bukuryo-gan, Tokaku-joki-to, Toki-shakuyaku-san) are administered in combination. Consequently, basic autonomic functions, such as appetite, sleep, defecation, and urination normalize and the nutritional and mental conditions are restored. These favorable changes in the patients' condition allow completion of the standard cancer therapy course, resultingin an improved outcome of cancer therapy and successful treatment. Kampo therapy can be administered as the final treatment option for patients with last-stage cancer who do not have any other effective therapy options. If patients with cancer are administered Kampo formulas, their vital energy is restored, and they develop a will to fight the cancer. As a result, communication becomes easier. PMID- 26809300 TI - [Current Status of Japanese Traditional Medicine 'Kampo' in Chemotherapy]. AB - Advancements in cancer chemotherapy and the introduction of Japanese traditional medicine"Kampo"have been successful in improving the prognosis of malignant tumors. Many Kampo drugs have been used in the treatment of adverse effects. We investigated the safety and efficacy of Hangeshashinto in the prevention and treatment of chemotherapy-induced oral mucositis in patients with gastric and colorectal cancer. Hangeshashinto was shown to reduce the risk of development of mucositis. We also investigated the efficacy of Goshajinkigan in the prevention of chemotherapy-induced neurotoxicity. Goshajinkigan appears to have a promising effect in delaying the onset of neurotoxicity of gradeB2 without reducing the efficacy of treatment. Kampo drugs such as Rikkunshito, Jyuzentaihoto, and Hochuekkito have also been used successfully in the prevention and treatment of chemotherapy-induced adverse effects. It is very important to know the efficacy and safety of Kampo drugs for alleviating the adverse effects of anticancer drugs in patients undergoing cancer treatment with chemotherapy. PMID- 26809301 TI - [Kampo Medicine in Perioperative Care for Cancer Patients]. AB - Operative stress causes various changes in the body, and immunological hypofunction and malnutrition increase complications and adversely affect long term prognosis. Therefore, reducing operative stress as much as possible, minimizing complications after surgery, and aiming for a satisfactory postoperative course are important. However, difficult and unresolvable situations often arise when only the conventional Western medicine approach is used because the situation and condition varies for each patient. We believe that Kampo medicine is very useful in diverse situations. Particularly, Kampo medicine has been used more frequently in recent years, with the expectation of numerous effects, because the effectiveness of Kampo medicine on various disease states has been proven and the pharmacological ingredients and the mechanisms by which Kampo medicine exerts its effects have been better clarified scientifically. Kampo medicine will have an effect in various situations, and we think that Kampo medicine occupies an important position in team-based medical care with multiple specialists. Kampo medicine compounds have been reported to be useful for the following conditions: Hochuekkito and Juzentaihoto for improving immunocompetence after operative stress, Daikenchuto and Rikkunshito for improving postoperative gastrointestinal motility, Shakuyakukanzoto for postoperative wound pain control, Yokukansan for postoperative delirium, and Inchinkoto for postoperative liver dysfunction. The availability of numerous treatment choices that work well in specific situations would be useful for cancer patients during the perioperative period. PMID- 26809302 TI - The Establishment of Indicators of Thrombocytopenia in Patients Receiving Lenalidomide Therapy. AB - The onset of thrombocytopenia and related factors was analyzed in patients with multiple myeloma (MM) who were receiving lenalidomide (Len) therapy at the Department of Hematology, Gifu Municipal Hospital between July 2010 and March 2014. We included 28 MM patients (18 males and 10 females) with a median age of 70.5 (range: 55-84) years. The patients were examined from the start of Len therapy until treatment discontinuation, prolongation, or dose reduction. A significant correlation was observed between platelet (Plt) count prior to the start of Len therapy (pre-treatment Plt) and the difference between pre-treatment Plt and the minimum Plt up to the point in time of treatment discontinuation, prolongation, or dosage reduction (min-Plt) (r=0.674, p<0.001). Univariate analysis revealed that factors causing thrombocytopenia of grade 2or above as a side-effect showed a significant difference when the Plt count was below the lower limit of the normal value (<14.0*10(4)/uL)(p=0.011). Factors with p<0.25 in the univariate analysis and daily dosage of Len were examined by multivariate analysis; thus, a Plt count below the lower limit of the normal value was identified as a factor (odds ratio: 15.12, 95% confidence interval [CI]: 1.712 133.5, p=0.015). In conclusion, we suggest that a Plt count below the lower limit of the normal value prior to the start of Len therapy is a prognostic factor for thrombocytopenia as a side-effect of Len therapy. PMID- 26809304 TI - [Examination of Measures for Preventing Exposure in Nurses Who Handle Cyclophosphamide]. AB - Health hazards due to long-term exposure to anticancer drugs have been reported among health care professionals. In Yamagata Prefectural Central Hospital, constant use of personal protective equipment(gloves and mask with face shield)is mandatory, but there is no clear description of the protective gown. To verify the exposure status of nurses while handling cyclophosphamide and the usefulness of a protective gown as a protective measure, urinary concentration of cyclophosphamide was measured for nurses who handled cyclophosphamide. No cyclophosphamide was detected in the urine samples collected from nurses who handled cyclophosphamide while wearing protective gowns or in the samples collected from nurses who handled cyclophosphamide without protective gowns. This finding suggests that gloves and a mask with a face shield are sufficient for preventing exposure to cyclophosphamide. However, considering that only experienced nurses were included as subjects in this study, we cannot conclude that a protective gown is unnecessary, because inexperienced nurses may be exposed to cyclophosphamide. Our study's findings may be one reference to examine measures for preventing exposure in nurses. PMID- 26809303 TI - [Gemcitabine Monotherapy for Advanced Mycosis Fungoides--Two Case Reports and a Literature Review]. AB - Gemcitabine, a pyrimidine nucleoside analogue, is gaining recognition as a potential therapeutic agent for advanced-stage and refractory cutaneous T-cell lymphoma (CTCL). We report of 2 patients whose advanced-stage mycosis fungoides was not sufficiently controlled by prior CHOP therapy. Both patients showed great improvement in the skin lesions with weekly gemcitabine therapy (1,000-1,200 mg/m2). The patients received four and 8 cycles of gemcitabine monotherapy, respectively, and no grade 3-4 hematological or hepatic adverse events occurred. This is the first report of the efficacy of gemcitabine for CTCL in Japan. Gemcitabine is well tolerated and is an effective monotherapy for CTCL. PMID- 26809305 TI - [Quality of Life Is Associated with Combined Lenalidomide and Dexamethasone Treatment in Japanese Patients with Relapsed or Refractory Multiple Myeloma]. AB - This study investigated the relationship between quality of life (QOL) and efficacy or occurrence of adverse events in patients who were administered lenalidomide and dexamethasone (Len+Dex) therapy for relapsed or refractory multiple myeloma (MM) in the hematology department at Obihiro Kosei Hospital from September 2010 to September 2012. QOL was evaluated using a quality of life questionnaire for cancer patients treated with anticancer drugs (QOL-ACD). The average QOL score of 7 patients receiving 4 cycles of Len+Dex treatment decreased 5 points from baseline Len+Dex treatment. The change in QOL score was significantly correlated with changes in serum M-protein (correlation coefficient: R=0.777). However, there was no significant correlation between adverse events and the change in QOL score. Our results indicate that QOL may be improved by the effects of Len+Dex treatment. PMID- 26809306 TI - [Onset of Syndrome of Inappropriate Secretion of Antidiuretic Hormone in a Gastric Cancer Patient on SOX Treatment]. AB - A 78-year-old man with advanced gastric cancer was treated with S-1 and oxaliplatin chemotherapy. He developed hiccups and nausea, and was diagnosed with hyponatremia (serum Na: 120 mEq/L) on day 6 of the first treatment course. Because of his increased urinary Na excretion and relatively high ADH values, he was subsequently diagnosed with chemotherapy-induced syndrome of inappropriate secretion of antidiuretic hormone. The patient recovered after an infusion of hypertonic saline. Although S-1 was restarted, hyponatremia did not recur. We suspected adverse drug reactions to ACE inhibitors and K-sparing diuretics in our case of hyponatremia. PMID- 26809307 TI - [HER2-Positive Advanced Gastric Cancer with Disseminated Intravascular Coagulation and Diffuse Bone Marrow Carcinomatosis Successfully Treated with S 1/Trastuzumab Chemotherapy--A Case Report]. AB - Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor 2 (HER2), has been proven to result in a survival benefit for the treatment of patients with HER2-positive advanced gastric cancer (AGC). However, data are lacking for the treatment of those with disseminated intravascular coagulation (DIC) and diffuse bone marrow carcinomatosis. A 77-year-old woman presented with back pain and fatigue since 2 months. Esophagogastroduodenoscopy showed a scirrhous lesion in the gastric corpus, which was biopsied and identified as signet-ring cell carcinoma with HER2 overexpression on immunohistochemistry. Laboratory testing, bone scintigraphy, and bone marrow biopsy were conducted, and she was diagnosed with HER2-positive AGC with DIC and diffuse bone marrow carcinomatosis. She underwent chemotherapy with the following regimen: oral administration of 80 mg/m2 S-1 for 2 weeks and 6 mg/kg trastuzumab infusion on day 6 every 3 weeks, which significantly improved the DIC. She was discharged from the hospital 73 days after admission and survived for 438 days after diagnosis. To the best of our knowledge, this is the first case report in which HER2-positive AGC complicated by DIC with diffuse bone marrow carcinomatosis was successfully treated with combined chemotherapy consisting of S-1 plus trastuzumab. PMID- 26809308 TI - [A Case of Signet-Ring Cell Carcinoma of the Sigmoid Colon with Disseminated Carcinomatosis Successfully Treated with CPT-11/Panitumumab]. AB - A 70-year-old man, who had undergone S-1/oxaliplatin/bevacizumab combination chemotherapy for LNs metastasis of signet-ring cell carcinoma of the sigmoid colon, complained of back pain and lumbago.He was diagnosed with disseminated carcinomatosis of the bone marrow and disseminated intravascular coagulation (DIC). He was treated with systemic chemotherapy consisting of CPT 11/panitumumab. After 2 courses of the treatment, the DIC resolved and the back pain and lumbago improved. PMID- 26809309 TI - [A Case of Rectal Cancer with Lymphangiosis Carcinomatosa Successfully Treated with Chemotherapy Despite Anaphylactic Reaction to Oxaliplatin]. AB - A 64-year-old man was admitted because of dyspnea. He was diagnosed with rectal cancer with lymphangiosis carcinomatosa and metastases in the liver and lymph nodes. The patient was treated with cetuximab and modified FOLFOX6 (mFOLFOX6). After treatment, the primary rectal cancer and metastases were considered to have achieved a partial response (PR) and the lymphangiosis carcinomatosa remarkably improved. However, anaphylactic shock occurred in the 6 courses of treatment, 5 minutes after the infusion of oxaliplatin, and the patient was treated. PMID- 26809310 TI - [Long-Term Survival of a Patient with Rectal Neuroendocrine Carcinoma after Treatment with Curative Resection and Adjuvant Chemotherapy with Capecitabine]. AB - A 63-year-old man who complained of hematochezia underwent colonoscopy, and a type 2 tumor was detected at the Rs portion. The tumor was initially diagnosed as a poorly differentiated adenocarcinoma by biopsy. Laparoscopy-assisted anterior resection with regional lymphadenectomy was performed, and pathological examination showed the tumor was a neuroendocrine carcinoma (NEC) with muscular invasion and lymph node metastasis. The Ki-67 index of the tumor was more than 70%. This patient underwent adjuvant chemotherapy with capecitabine for 6 months and is now alive without recurrence, more than 40 months after surgery. Although the prognosis of NEC is generally poor, capecitabine might be effective as an adjuvant chemotherapy regimen after curative resection. PMID- 26809311 TI - [A Case of Rectal Cancer with Multiple Liver, Lung, and Para-Aortic Lymph Node Metastases Successfully Treated with FOLFOX4 plus Bevacizumab]. AB - A patient in his 70s was diagnosed with rectal cancer (pT3, pN1, cM0, and pStage IIIa) for which he underwent low anterior resection of the rectum and received adjuvant therapy with UFT/LV. Multiple liver, lung, and para-aortic lymph node metastases were detected after 6 months, and the patient then received a total of 24 courses of FOLFOX4 plus bevacizumab instead of UFT/LV. The liver and para aortic lymph node metastases showed a complete response (CR), and the lung metastases markedly diminished. Therefore, the patient completed the FOLFOX4 plus bevacizumab chemotherapy regimen. After 2 years, a recurrence of the initial liver metastases was detected. A CR on radiological imaging does not correspond to a pathological CR. Therefore, a careful follow-upis required even when a CR on radiological imaging is achieved. PMID- 26809312 TI - [Life-Threatening Hyponatremia by Chemotherapy in a Patient with Non-Hodgkin's Lymphoma]. AB - Cyclophosphamide and vincristine are known to be the chemotherapeutic agents most frequently associated with hyponatremia. Here, we report the case of a 69-year old man with non-Hodgkin's lymphoma who developed severe hyponatremia during chemotherapy. The Japanese man was diagnosed with diffuse large B-cell lymphoma, and underwent chemotherapy treatment with THP-COP (cyclophosphamide, pirarubicin, vincristine, and prednisolone). In the first course of chemotherapy, he developed hyponatremia (nadir 109 mEq/L) and his urinary N-acetyl-beta-D-glucosaminidase (NAG) level had increased. After the second courses of chemotherapy with rituximab, pirarubicin, and prednisolone, without cyclophosphamide and vincristine, he had developed light hyponatremia (nadir 130 mEq/L). However, after the third and fourth courses of chemotherapy with rituximab, pirarubicin, prednisolone, and cyclophosphamide, he had developed a medium level of hyponatremia (nadir 124-125 mEq/L) and his NAG level had increased further. The possible mechanism of this phenomenon is due to renal tubular damage by cyclophosphamide. We conclude that extra caution is necessary if a patient develops severe hyponatremia following chemotherapeutic treatment with cyclophosphamide and vincristine. PMID- 26809313 TI - [A Case of Delayed Vascular Injury as a Complication Related to Implanted Central Venous Port Catheter]. AB - A 74-year-old woman with advanced gastric cancer was admitted to our hospital. A central venous (CV) port catheter was implanted into the right subclavian vein for preoperative chemotherapy and parenteral nutritional management. On the 35th day after implantation, she complained of diarrhea, fever and dyspnea. The chest radiograph showed a right-sided massive pleural effusion. As the patient progressively fell into severe respiratory distress, endotracheal intubation was performed for management of respiration by mechanical ventilation. Initially, given the patient's symptoms, she was diagnosed with septic shock. Therefore, after placement of a CV catheter through the right femoral vein, in consideration of the possibility of a port infection, she was treated with thoracentesis and infusion of antibiotics. The patient gradually recovered, and again received parenteral nutrition through the CV port catheter. After the infusion was administered, she complained of dyspnea. A CT scan of the chest revealed a right pleural effusion and displacement of the tip of the CV port catheter out of the wall of the superior vena cava. We diagnosed delayed vascular injury (DVI), and the CV port catheter was removed. She soon recovered with conservative treatment. We speculated that the initial respiratory symptoms such as the pleural effusion were caused by DVI. DVI should therefore be recognized as a complication related to implanted CV port catheters. PMID- 26809314 TI - Airflows generated by an impacting drop. AB - A drop impacting a solid surface with sufficient velocity will splash and emit many small droplets. However, lowering the ambient air pressure suppresses splashing completely. This effect, robustly found for different liquid and substrate properties, raises the fundamental question of how air affects a spreading drop. In a combined experimental and numerical study we characterize the flow of air induced by the drop after it hits the substrate, using a modified Schlieren optics technique combined with high-speed video imaging and Lattice Boltzmann simulations. Our experiments reveal the emergence of air structures on different length scales. On large scales, the airflow induced in the drop's wake leads to vortex structures due to interaction with the substrate. On smaller scales, we visualize a ring structure above the outer edge of the spreading liquid generated by the spreading of the drop. Our simulations reveal the interaction between the wake vorticity and the flows originating from the rapidly escaping air from below the impacting drop. We show that the vorticity is governed by a balance between inertial and viscous forces in the air, and is unrelated to the splashing threshold. PMID- 26809317 TI - The ameliorative effect of Monascus purpureus NTU 568-fermented rice extracts on 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells and the rat model of Parkinson's disease. AB - Oxidative stress and neuroinflammation underlie the major pathogenesis in Parkinson's disease (PD). Antioxidants are known to protect against the degeneration of dopaminergic neurons. Monascus purpureus-fermented rice, a traditional Chinese medicine as well as a health food, includes multifunctional metabolites. The present study was designed to investigate the effects of the antioxidant-containing M. purpureus NTU 568-fermented rice extract (extracted with 50% ethanol, so called R50E) in 6-hydrodopamine (6-OHDA)-induced neurotoxicity in vitro and in vivo. In vitro, treatment with R50E reduced 6-OHDA induced SH-SY5Y cell death. In vivo, two doses of R50E (5.5 and 11.0 mg kg(-1)) were administered for a period of 28 days following 6-OHDA-induced lesioning. The administration of R50E reduced parkinsonian motor dysfunction and the number of tyrosine hydroxylase (TH)-immunoreactive neurons present in 6-OHDA-induced lesioned rats. Moreover, the administration of R50E reversed the elevation of reactive oxygen species (ROS) and malondialdehyde (MDA) levels and promoted the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione reductase, and glutathione peroxidase via down-regulation of p47 phox, NOX1, and NOX2 expression in the 6-OHDA-lesion rats. Furthermore, treatment with R50E attenuated nitric oxide (NO) and tumor necrosis factor (TNF-alpha) levels in the 6-OHDA-lesion rats. In conclusion, R50E may prevent neurodegeneration via anti-oxidative and anti-inflammatory mechanisms, suggesting its potential therapeutic value for PD treatment. This is the first study for evaluating the neuroprotective effects of red mold fermented products in PD models. PMID- 26809315 TI - Parallel Evolution of Copy-Number Variation across Continents in Drosophila melanogaster. AB - Genetic differentiation across populations that is maintained in the presence of gene flow is a hallmark of spatially varying selection. In Drosophila melanogaster, the latitudinal clines across the eastern coasts of Australia and North America appear to be examples of this type of selection, with recent studies showing that a substantial portion of the D. melanogaster genome exhibits allele frequency differentiation with respect to latitude on both continents. As of yet there has been no genome-wide examination of differentiated copy-number variants (CNVs) in these geographic regions, despite their potential importance for phenotypic variation in Drosophila and other taxa. Here, we present an analysis of geographic variation in CNVs in D. melanogaster. We also present the first genomic analysis of geographic variation for copy-number variation in the sister species, D. simulans, in order to investigate patterns of parallel evolution in these close relatives. In D. melanogaster we find hundreds of CNVs, many of which show parallel patterns of geographic variation on both continents, lending support to the idea that they are influenced by spatially varying selection. These findings support the idea that polymorphic CNVs contribute to local adaptation in D. melanogaster In contrast, we find very few CNVs in D. simulans that are geographically differentiated in parallel on both continents, consistent with earlier work suggesting that clinal patterns are weaker in this species. PMID- 26809318 TI - Short-range plasmonic nanofocusing within submicron regimes facilitates in situ probing and promoting of interfacial reactions. AB - In this study, a simple configuration, based on high-index dielectric nanoparticles (NPs) and plasmonic nanostructures, is employed for the nanofocusing of submicron-short-range surface plasmon polaritons (SPPs). The excited SPPs are locally bound and focused at the interface between the dielectric NPs and the underlying metallic nanostructures, thereby greatly enhancing the local electromagnetic field. Taking advantage of the surface properties of the dielectric NPs, this system performs various functions. For example, the nanofocusing of submicron-short-range SPPs is used to enhance the Raman signals of gas molecules adsorbed on the dielectric NPs. In addition, the presence of the local strong electromagnetic field accelerates the rates of interfacial reactions on the surfaces of the dielectric NPs. Therefore, the proposed nanofocusing configuration can both promote and probe interfacial reactions simultaneously. Herein, the promotion and probing of the desorption of EtOH vapor are described, as well as the photodegradation of methylene blue. Moreover, the nanofocusing of SPPs is demonstrated on an aluminum surface in both the visible and UV regimes, a process that has not been achieved using conventional tapered waveguide nanofocusing structures. Therefore, the nanofocusing of submicron-short-range SPPs by dielectric NPs on plasmonic nanostructures is not limited to low-loss noble metals. Accordingly, this system has potential for use in light management and on-chip green devices and sensors. PMID- 26809319 TI - Wisdom of Microbial Pathogens: A Novel Approach to Develop Antimicrobials Against Methicillin-Resistant Staphylococcus aureus. PMID- 26809321 TI - Academic Training in Vestibular and Balance Function Testing Does Not Ensure Audiologists Will Be the Preferred Providers. PMID- 26809322 TI - Risk Factors for Hearing Loss in Patients with Cystic Fibrosis. AB - BACKGROUND: Patients with cystic fibrosis (CF) are at increased risk for sensorineural hearing loss (SNHL) due, at least in part, to the ototoxic side effects of routine CF therapies. However, the prevalence of SNHL and additional factors contributing to the development of SNHL are unknown. PURPOSE: To identify risk factors associated with the development of SNHL in a large cohort of CF patients who had been referred for audiometric testing. RESEARCH DESIGN: A retrospective study of audiometric results and medication information in a cohort of patients with CF. STUDY SAMPLE: Records of 178 CF patients seen at Boston Children's Hospital for audiometric testing from 2007 to 2010 were reviewed. Mean age of patients was 18 yr (standard deviation = 10 yr), and 98 (55%) of the patients were female. DATA COLLECTION AND ANALYSIS: Audiometric results, medications, and hospitalizations were recorded. Multivariable logistic regression was used to evaluate the association between SNHL and the number of hospitalizations and chronic antibiotic use in the year prior to the patients' audiometry. RESULTS: In this sample, 37/178 (21%) patients had SNHL. Twenty-nine (78%) of the 37 patients had bilateral SNHL and 8 (22%) had unilateral SNHL. Across all age groups, the majority of patients had a bilateral hearing loss (HL). A multivariable model showed that older age and more frequent hospitalizations were associated with SNHL. The number of courses of chronic antibiotics in the year prior to audiometric testing was not correlated with rate of HL. CONCLUSIONS: This study suggests that age and frequency of hospitalizations are key predictors of HL development. Increased awareness and regular screening for SNHL should be included in the routine care of CF patients, particularly those at the highest risk. PMID- 26809323 TI - The Effect of Lexical Content on Dichotic Speech Recognition in Older Adults. AB - BACKGROUND: Age-related auditory processing deficits have been shown to negatively affect speech recognition for older adult listeners. In contrast, older adults gain benefit from their ability to make use of semantic and lexical content of the speech signal (i.e., top-down processing), particularly in complex listening situations. Assessment of auditory processing abilities among aging adults should take into consideration semantic and lexical content of the speech signal. PURPOSE: The purpose of this study was to examine the effects of lexical and attentional factors on dichotic speech recognition performance characteristics for older adult listeners. RESEARCH DESIGN: A repeated measures design was used to examine differences in dichotic word recognition as a function of lexical and attentional factors. STUDY SAMPLE: Thirty-five older adults (61-85 yr) with sensorineural hearing loss participated in this study. DATA COLLECTION AND ANALYSIS: Dichotic speech recognition was evaluated using consonant-vowel consonant (CVC) word and nonsense CVC syllable stimuli administered in the free recall, directed recall right, and directed recall left response conditions. RESULTS: Dichotic speech recognition performance for nonsense CVC syllables was significantly poorer than performance for CVC words. Dichotic recognition performance varied across response condition for both stimulus types, which is consistent with previous studies on dichotic speech recognition. Inspection of individual results revealed that five listeners demonstrated an auditory-based left ear deficit for one or both stimulus types. CONCLUSIONS: Lexical content of stimulus materials affects performance characteristics for dichotic speech recognition tasks in the older adult population. The use of nonsense CVC syllable material may provide a way to assess dichotic speech recognition performance while potentially lessening the effects of lexical content on performance (i.e., measuring bottom-up auditory function both with and without top-down processing). PMID- 26809324 TI - The Effects of Hearing Aid Directional Microphone and Noise Reduction Processing on Listening Effort in Older Adults with Hearing Loss. AB - BACKGROUND: Older listeners with hearing loss may exert more cognitive resources to maintain a level of listening performance similar to that of younger listeners with normal hearing. Unfortunately, this increase in cognitive load, which is often conceptualized as increased listening effort, may come at the cost of cognitive processing resources that might otherwise be available for other tasks. PURPOSE: The purpose of this study was to evaluate the independent and combined effects of a hearing aid directional microphone and a noise reduction (NR) algorithm on reducing the listening effort older listeners with hearing loss expend on a speech-in-noise task. RESEARCH DESIGN: Participants were fitted with study worn commercially available behind-the-ear hearing aids. Listening effort on a sentence recognition in noise task was measured using an objective auditory visual dual-task paradigm. The primary task required participants to repeat sentences presented in quiet and in a four-talker babble. The secondary task was a digital visual pursuit rotor-tracking test, for which participants were instructed to use a computer mouse to track a moving target around an ellipse that was displayed on a computer screen. Each of the two tasks was presented separately and concurrently at a fixed overall speech recognition performance level of 50% correct with and without the directional microphone and/or the NR algorithm activated in the hearing aids. In addition, participants reported how effortful it was to listen to the sentences in quiet and in background noise in the different hearing aid listening conditions. STUDY SAMPLE: Fifteen older listeners with mild sloping to severe sensorineural hearing loss participated in this study. RESULTS: Listening effort in background noise was significantly reduced with the directional microphones activated in the hearing aids. However, there was no significant change in listening effort with the hearing aid NR algorithm compared to no noise processing. Correlation analysis between objective and self-reported ratings of listening effort showed no significant relation. CONCLUSIONS: Directional microphone processing effectively reduced the cognitive load of listening to speech in background noise. This is significant because it is likely that listeners with hearing impairment will frequently encounter noisy speech in their everyday communications. PMID- 26809325 TI - Diagnostic Hearing Assessment in Schools: Validity and Time Efficiency of Automated Audiometry. AB - BACKGROUND: Poor follow-up compliance from school-based hearing screening typically undermines the efficacy of school-based hearing screening programs. Onsite diagnostic audiometry with automation may reduce false positives and ensure directed referrals. PURPOSE: To investigate the validity and time efficiency of automated diagnostic air- and bone-conduction audiometry for children in a natural school environment following hearing screening. RESEARCH DESIGN: A within-subject repeated measures design was employed to compare air- and bone-conduction pure-tone thresholds (0.5-4 kHz), measured by manual and automated pure-tone audiometry. STUDY SAMPLE: Sixty-two children, 25 males and 37 females, with an average age of 8 yr (standard deviation [SD] = 0.92; range = 6 10 yr) were recruited for this study. The participants included 30 children who failed on a hearing screening and 32 children who passed a hearing screening. DATA ANALYSIS: Threshold comparisons were made for air- and bone-conduction thresholds across ears tested with manual and automated audiometry. To avoid a floor effect thresholds of 15 dB HL were excluded in analyses. The Wilcoxon signed ranked test was used to compare threshold correspondence for manual and automated thresholds and the paired samples t-test was used to compare test time. Statistical significance was set as p <= 0.05. RESULTS: 85.7% of air-conduction thresholds and 44.6% of bone-conduction thresholds corresponded within the normal range (15 dB HL) for manual and automated audiometry. Both manual and automated audiometry air- and bone-conduction thresholds exceeded 15 dB HL in 9.9% and 34.0% of thresholds, respectively. For these thresholds, average absolute differences for air- and bone-conduction thresholds were 6.3 (SD = 8.3) and 2.2 dB (SD = 3.6) and they corresponded within 10 dB across frequencies in 87.7% and 100.0%, respectively. There was no significant difference between manual and automated air- and bone-conduction across frequencies for these thresholds. CONCLUSION: Using onsite automated diagnostic audiometry for children who fail hearing screening may improve the efficacy of school-based screening programs by reducing false positives and ensuring directed referrals for audiological or medical intervention or both. PMID- 26809327 TI - Hearing Loss Terminology: In Response to Wilson and Margolis (2015). PMID- 26809326 TI - Preservation of Neural Sensitivity after Noise-Induced Suppression of Sensory Function. AB - BACKGROUND: Permanent loss of outer hair cell (OHC) amplification may occur within days of acoustic overexposure. This loss of sensory function typically results in an immediate loss of neural sensitivity although neurodegeneration occurs months or years after damage to OHCs. This delay in neurodegeneration might provide an opportunity to preserve neural sensitivity although OHC amplification is permanently lost. PURPOSE: To test the hypothesis that neural functions can be preserved after permanent and severe loss of OHC amplification. To begin to address this possibility, an animal model of severe permanent loss of both OHC and neural functions was established. RESEARCH DESIGN: This research employed a 4 * 4 split-plot factorial design, with four levels of the within subject factor (time: baseline, 1-day, 1-week, and 1-mo postnoise exposure) and four levels of the between-subject factor (experimental groups: control, noise exposed, therapy, and noise exposed + therapy). STUDY SAMPLE: Twenty-six hooded male Long-Evans rats (263 +/- 63 g) served as subjects for this experiment. All animals exhibited baseline auditory function that approximated normative values for rats of the same strain. DATA COLLECTION AND ANALYSIS: Distortion product otoacoustic emissions and auditory brainstem responses were used to assay and differentiate OHC versus neural functions. Factorial analysis of variances was computed to identify statistically significant main effects and Dunnett testing was employed in post hoc computations. INTERVENTION: To rescue neural function after permanent loss of OHC amplification, small molecular weight carboxy alkyl esters were employed after noise injury. RESULTS: The results revealed that in the presence of permanent loss of OHC amplification, the loss of neural sensitivity could be rescued. In addition, auditory brainstem response wave I amplitudes at suprathreshold levels were rescued from noise-induced depletion into the biologic noise floor. CONCLUSION: Since mammalian OHCs do not regenerate after damage, these results encourage further experiments aimed at preserving neural functions following noise injury. PMID- 26809328 TI - Correction: Loudness as a Cue for Acceptable Noise Levels. PMID- 26809333 TI - The Secondary Quality Indicator to Improve Prediction of Adenoma Miss Rate Apart from Adenoma Detection Rate. AB - OBJECTIVES: Adenoma detection rate (ADR) cannot distinguish between endoscopists who detect one adenoma and those who detect >=2 adenomas. Hypothetically, adenoma miss rate (AMR) may be significant for endoscopists with high ADRs who examine the rest of colon with less care after detecting first polyp. Our objective was to evaluate other quality indicators plus ADR vs. ADR alone in prediction of AMR. METHODS: We conducted a cross-sectional study of asymptomatic participants aged 50-75 years who underwent back-to-back screening colonoscopies by four faculty endoscopists. Each round of colonoscopy was performed by two of the endoscopists in a randomized order. During each round of colonoscopy, all detected polyps were removed. The second endoscopist was blinded to the results of the first. The total number of adenomas per positive participant (APP), the total number of adenomas per colonoscopy (APC), the additional adenomas found after the first adenoma per colonoscopy (ADR-Plus), and ADR were calculated for prediction of AMR. RESULTS: In all, 200 participants underwent back-to-back colonoscopies. There were no significant differences in ADRs of four endoscopists (44, 50, 54, and 46%). APPs were 1.91, 2.12, 2.19, and 2.43. APCs were 0.84, 1.06, 1.18, and 1.12. ADR-Plus were 0.40, 0.56, 0.64, and 0.66, respectively. AMRs differed significantly between the endoscopists (36, 27, 21, and 13%; P=0.01). There was no correlation between ADR and AMR (r=-0.25; P=0.75). Whereas APP exhibited a strong inverse correlation with AMRs (r=-0.99; P<0.01). APC and ADR-Plus appeared to be inversely correlated with AMR, however this was not statistically significant (r=-0.82; P=0.18 and r=-0.93; P=0.07, respectively). CONCLUSIONS: Among high-ADR endoscopists, AMRs still varied. APP may be a promising secondary indicator for distinguishing between the one-and-done polyp endoscopist and the meticulous endoscopist. The evaluation of influence of new metrics on colorectal cancer (CRC) prevention requires a larger population-based study. PMID- 26809337 TI - Cultural Socialization Across Contexts: Family-Peer Congruence and Adolescent Well-Being. AB - Racial/ethnic minority youth live at the intersection of diverse cultures, yet little is known about cultural socialization outside families or how cultural socialization in multiple settings conjointly influences adolescent well-being. In a sample of 236 8th graders (51 % female; 89 % Latinos, 11 % African Americans), we examined adolescents' perceptions of family and peer cultural socialization toward the heritage culture and the mainstream American culture. A variable-centered approach demonstrated that the socioemotional and academic benefits of family cultural socialization were most evident when peer cultural socialization was congruently high. Although family and peer cultural contexts are often assumed to be drastically different, we identified similar proportions of adolescents experiencing congruently high, congruently low, and incongruent cultural socialization from families and peers using a person-centered approach. Although the incongruent group received relatively high levels of cultural socialization in one setting, their well-being was similar to the congruently low group. The findings highlight the importance of considering cultural socialization across multiple developmental settings in understanding racial/ethnic minority youth's well-being. PMID- 26809339 TI - Big Data and Its Role in Health Economics and Outcomes Research: A Collection of Perspectives on Data Sources, Measurement, and Analysis. PMID- 26809340 TI - Assessment of productivity of Culex spp. larvae (Diptera: Culicidae) in urban storm water catch basin system in Wroclaw (SW Poland). AB - In urban environments, catch basins serve as major developmental and resting sites for anthropophilic and zoophilic mosquitoes. However, the use of this habitat is inconsistent, with abundance of larvae varying significantly across catch basins at a fine spatial scale. During seasonal summer investigations on mosquito species composition, their spatial and temporal distribution and the environmental characteristic of the breeding sites in the underground storm drain systems of the Wroclaw urban area (SW Poland) were assessed from May to September in 2012-2013. The study was conducted in order to develop a rational strategy to control mosquito populations and prevent the potential human exposure to mosquito transmitted pathogens. Mosquito larvae and pupae were collected and identified weekly from 100 regularly inspected street catch basins located in the town center. All existing and potential breeding habitats in the study area were recorded using a GPS receiver (Magellan MobileMapper CX) and transferred to the computer database. Collected data on the geographical location of inspected breeding places, water quality parameters in inspected catch basins, daily temperature, and precipitation were imposed on orthophotomap in ArcGIS (ESRI, USA). Water quality parameters including pH, electrical conductivity, and water temperature were measured by standard methods. Chemical water analysis of cations (Na(+), NH4 (+), K(+), Mg(2+), Ca(2+)) and anions (Cl(-), NO2 (-), NO3 (-), SO4 (2-)) were carried out using Waters Alliance high-performance liquid chromatograph (HPLC) 2695 with 432 Conductivity Detector and 2998 Photodiode Array Detector, an IC-Pak Anion HR column (glauconate/borate eluent) and IC-Pak Cation M/D column (EDTA/HNO3 eluent). Over two seasonal studies and 3739 samplings in total, 3669 mosquito larvae and 274 pupae/1 dip (from 0 to 110 individuals/dip) were collected by dipper. Culex pipiens s.l. (L.) and Cx. torrentium (Martini) prevailed at all catch basins of the study area as the predominant species. In all examined catch basins, autogenous individuals dominated by far. Breeding activity was first detected in early May. Peak abundance of Culex spp. population in many catch basins was observed in June 2012 and August 2013 when average daily temperatures were increasing and rainfall had declined. Dry periods between rainfalls varied during 2 years of the study period and were noted on June 2012 as well as on July and August 2013. Organically enriched catch basins with significant higher concentrations of Na(+) and NO3 (-) were found to be more productive breeding habitats. Differences in the Culex immature stage density based on the variables of habitat type, temperature, and precipitation support the need for ongoing surveillance in communities to guide public health officials in planning for and prioritizing mosquito control efforts. PMID- 26809341 TI - Blood-stage malaria of Plasmodium chabaudi induces differential Tlr expression in the liver of susceptible and vaccination-protected Balb/c mice. AB - Protective vaccination induces self-healing of otherwise lethal blood-stage infections of Plasmodium chabaudi malaria. Here, we investigate mRNA expression patterns of all 12 members of the Toll-like receptor (Tlr) gene family in the liver, a major effector organ against blood-stage malaria, during lethal and vaccination-induced self-healing infections of P. chabaudi in female Balb/c mice. Gene expression microarrays reveal that all 12 Tlr genes are constitutively expressed, though at varying levels, and specifically respond to infection. Protective vaccination does not affect constitutive expression of any of the 12 Tlr genes but leads to differential expression (p < 0.05) of seven Tlrs (1, 2, 4, 7, 8, 12, and 13) in response to malaria. Quantitative PCR substantiates differential expression at p < 0.01. There is an increased expression of Tlr2 by approximately five-fold on day 1 post-infection (p.i.) and Tlr1 by approximately threefold on day 4 p.i.. At peak parasitemia on day 8 p.i., none of the 12 Tlrs display any differential expression. After peak parasitemia, towards the end of the crisis phase on day 11 p.i., expression of Tlrs 1, 4, and 12 is increased by approximately four-, two-, and three-fold, respectively, and that of Tlr7 is decreased by approximately two-fold. Collectively, our data suggest that though all 12 members of the Tlr gene family are specifically responsive to malaria in the liver, not only Tlr2 at the early stage of infection but also the Tlrs 1, 4, 7, and 12 towards the end of crisis phase are critical for vaccination-induced resolution and survival of otherwise lethal blood-stage malaria. PMID- 26809342 TI - Good syndrome and other causes of cytomegalovirus retinitis in HIV-negative patients-case report and comprehensive review of the literature. AB - We describe a 65-year-old Thai woman who developed cytomegalovirus retinitis (CMVR) in the setting of Good syndrome-a rare, acquired partial immune deficiency caused by thymoma. The patient subsequently developed vitritis with cystoid macular edema (CME) similar to immune recovery uveitis (IRU) despite control of the retinitis with antiviral agents. A comprehensive review of the literature through December, 2014, identified an additional 279 eyes of 208 patients with CMVR in the absence of human immunodeficiency virus (HIV) infection. Including our newly reported case, 9 of the 208 patients (4.3 %) had Good syndrome. Twenty one of the 208 patients (10.1 %) had CMVR related to intraocular or periocular corticosteroid administration. The remaining 178 patients (85.6 %) acquired CMVR from other causes. Within the subset of patients who did not have Good syndrome or did not acquire CMVR followed by intraocular or periocular corticosteroid administration, there were many other factors contributing to a decline in immune function. The most common included age over 60 years (33.1 %), an underlying malignancy (28.7 %), a systemic autoimmune disorder requiring systemic immunosuppression (19.1 %), organ (15.2 %) or bone marrow (16.3 %) transplantation requiring systemic immunosuppression, and diabetes mellitus (6.1 %). Only 4.5 % of the patients had no identifiable contributor to a decline in immune function. While the clinical features of CMVR are generally similar in HIV negative and HIV-positive patients, the rates of moderate to severe intraocular inflammation and of occlusive retinal vasculitis appear to be higher in HIV negative patients. PMID- 26809343 TI - Osteogenic differentiation of bone marrow stromal cells is hindered by the presence of intervertebral disc cells. AB - BACKGROUND: Clinical observations indicate that the presence of nucleus pulposus (NP) tissue during spinal fusion hinders the rate of disc ossification. While the underlying mechanism remains unknown, this observation could be due to incomplete removal of NP cells (NPCs) that secrete factors preventing disc calcification, such as bone morphogenetic protein (BMP) antagonists including noggin and members of the DAN (differential screening selected gene aberrative in neuroblastoma) family. METHODS: Monolayer human bone marrow-derived mesenchymal stem cells (MSCs) were cocultured withNPCs and annulus fibrosus cells (AFCs) embedded in alginate for 21 days. At the end of coculture, MSCs were stained for mineral deposition by alizarin red, and relative expression of bone-related genes [Runt related transcription factor 2, (RUNX2), Osteopontin (OPN), and Alkaline phosphatase (ALP)] and ALP activity were analyzed. Relative expression of three BMP antagonists, chordin (CHRD), gremlin (GREM1), and noggin (NOG), was determined in primary human NPCs and AFCs. These cells were also stained for Gremlin and Noggin by immunocytochemistry. RESULTS: Alizarin red staining showed that MSC osteogenesis in monolayer cultures was inhibited by coculture with NPCs or AFCs. ALP activity and RT-PCR analyses confirmed these results and demonstrated inhibition of osteogenesis of MSC in the presence of disc cells. NOG was significantly up-regulated in MSCs after coculture. Relative gene expression of intervertebral disc (IVD) cells showed higher expression of GREM1 in NPCs than in AFCs. CONCLUSIONS: We show that primary IVD cells inhibit osteogenesis of MSCs. BMP inhibitors NOG, GREM1 and CHRD were expressed in IVD cells. GREM1 appears to be differentially expressed in NPCs and AFCs. Our results have implications for the design and development of treatments for non-union in spinal fusion. PMID- 26809344 TI - Text Reminders in Colorectal Cancer Screening (TRICCS): Protocol for a randomised controlled trial. AB - BACKGROUND: Screening with the guaiac faecal occult blood test (gFOBt) is associated with improved colorectal cancer (CRC) survival, and is offered biennially to men and women aged 60-74 years in England's national Bowel Cancer Screening Programme (BCSP). Uptake of the gFOBt is low, with only 54 % of the eligible population completing the test. Text-message reminders could improve uptake of gFOBt. METHODS/DESIGN: This paper describes the protocol for a randomised controlled trial, which will examine the effectiveness of a text message reminder to promote uptake of gFOBt screening in the BCSP. Individual mobile telephone data from 180 general practices in London with existing mobile health services will be linked to the national BCSP information system via a secure on-line network. All screening-eligible adults registered with a participating practice will be randomised, to receive either usual care (N = 1600) or usual care plus a text-message reminder to self-complete and return their kit eight weeks after their initial invitation (N = 1600). The primary outcome will be the proportion of individuals who return an adequately completed gFOBt kit within 18 weeks of the initial invitation. Differences in uptake between groups will be evaluated using a logistic regression analysis, adjusting for individual-level and area-level socio-demographic variables. DISCUSSION: This will be the first large-scale randomised trial of a text-message reminder in a national screening programme for CRC. If effective, this study provides a cost effective means to promote uptake of CRC screening in an organised programme. TRIAL REGISTRATION: Current Controlled Trials ISRCTN70904476 (18/09/2015). PMID- 26809345 TI - Distinct prion-like strains of amyloid beta implicated in phenotypic diversity of Alzheimer's disease. AB - Vast evidence on human prions demonstrates that variable disease phenotypes, rates of propagation, and targeting of distinct brain structures are determined by unique conformers (strains) of pathogenic prion protein (PrP(Sc)). Recent progress in the development of advanced biophysical tools that inventory structural characteristics of amyloid beta (Abeta) in the brain cortex of phenotypically diverse Alzheimer's disease (AD) patients, revealed unique spectrum of oligomeric particles in the cortex of rapidly progressive cases, implicating these structures in variable rates of propagation in the brain, and in distict disease manifestation. Since only ~30% of phenotypic diversity of AD can be explained by polymorphisms in risk genes, these and transgenic bioassay data argue that structurally distinct Abeta particles play a major role in the diverse pathogenesis of AD, and may behave as distinct prion-like strains encoding diverse phenotypes. From these observations and our growing understanding of prions, there is a critical need for new strain-specific diagnostic strategies for misfolded proteins causing these elusive disorders. Since targeted drug therapy can induce mutation and evolution of prions into new strains, effective treatments of AD will require drugs that enhance clearance of pathogenic conformers, reduce the precursor protein, or inhibit the conversion of precursors into prion-like states. PMID- 26809347 TI - Autologous platelet lysate local injections for the treatment of refractory lateral epicondylitis. AB - BACKGROUND: The purpose of this study was to investigate the efficacy and safety of autologous platelet lysate (APL) local injections in reducing pain and improving function in patients with refractory lateral epicondylitis. METHODS: A total of 56 patients with refractory lateral epicondylitis were enrolled in this study. All the patients received three injections in one course of treatment. Subjective assessments include visual analog scale (VAS) pain score and Mayo elbow score before injection (baseline) and at 1, 6, and 12 months after injection. RESULTS: Significant differences were observed in VAS and Mayo scores at baseline and at 1, 6, and 12 months after injection. Overall, the injections of APL improved local symptoms and all the patients recovered to normal elbow function with 12 months follow-up. CONCLUSIONS: Local injections of APL resulted in favorable clinical outcomes for the treatment of lateral epicondylitis. APL could be clinically effective in the treatment of lateral epicondylitis. PMID- 26809350 TI - Honoring Patient Preferences in Initiation of Dialysis: Problems, Proposals, and a Path Forward. PMID- 26809346 TI - Additive anti-inflammatory effects of corticosteroids and phosphodiesterase-4 inhibitors in COPD CD8 cells. AB - BACKGROUND: CD8 lymphocytes play an important role in the pathogenesis of COPD. Corticosteroids and phosphodiesterase 4 (PDE4) inhibitors are anti-inflammatory drugs used for COPD treatment. Little is known of the combined effect of these drugs on COPD CD8 cells. We studied the effect of corticosteroid combined with PDE4 inhibitors on cytokine release form circulating and pulmonary CD8 cells, and on glucocorticoid (GR) nuclear translocation. METHODS: The effect of dexamethasone alone and in combination with the PDE4 inhibitors roflumilast and GSK256066 on cytokine release from circulating and pulmonary CD8 cells was measured. The effect of the compounds on nuclear translocation of GR and cyclic AMP-responsive element-binding protein (CREB) was studied using immunofluorescence. RESULTS: Dexamethasone inhibited cytokine release from COPD CD8 cells in a concentration dependent manner. PDE4 inhibitors enhanced this anti inflammatory effect in an additive manner. PDE4 inhibitors did not increase corticosteroid induced GR nuclear translocation. PDE4 inhibitors, but not corticosteroid, increased phospho-CREB nuclear translocation. CONCLUSION: The combination of corticosteroids and PDE4 inhibitors results in an additive anti inflammatory effect in COPD CD8 cells. This enhanced anti-inflammatory effect could translate to important clinical benefits for patients with COPD. PMID- 26809351 TI - An open-label pilot study of icariin for co-morbid bipolar and alcohol use disorder. AB - OBJECTIVES: Bipolar disorder is associated with a very high prevalence of alcohol related disorders. However, few studies have examined treatment in this population. Preclinical research suggests a role for the flavonoid icariin in mood and addictive disorders. In this open-label pilot study, we investigated the feasibility and safety of using icariin for persons with bipolar disorder and alcohol abuse or dependence. METHODS: Ten participants with bipolar I or bipolar II disorders, currently depressed, and with active alcohol abuse or dependence were given open-label icariin of up to 300 mg/day for 8 weeks using a flexible dosing strategy. Participants were assessed using the Hamilton Rating Scale for Depression (HAMD), Quick Inventory of Depressive Symptomatology-Self Report (QIDS SR), Hamilton Rating Scale for Anxiety (HAMA), and Young Mania Rating Scale (YMRS). Standard drinks, heavy drinking days, and drinking days were also quantified. Baseline and exit data were analyzed using the Wilcoxon Signed Rank Test. RESULTS: We observed a significant decrease in the HAMD (p = 0.012, d = 0.8), QIDS (p = 0.017, d = 0.7), and HAMA (p = 0.005, d = 1.4) scores. Heavy drinking days (p = 0.034, d = 1.1) and standard drinks (p = 0.038, d = 0.8) also decreased significantly. Icariin was well tolerated and no participants withdrew due to side-effects. CONCLUSION: Results from this uncontrolled study suggest icariin may decrease depressive symptoms and reduce alcohol consumption in persons with bipolar disorder and alcohol use. Improvement in mood and alcohol use was similar to that observed in an open-label trial of naltrexone in this population. Controlled trials, but at this point not routine clinical use, of icariin seem warranted. PMID- 26809352 TI - Novel CdS Hole-Blocking Layer for Photostable Perovskite Solar Cells. AB - Currently, the stability issue of the perovskite solar cells (PSCs) is one of the most critical obstacles in the commercialization of PSCs. Although incredible advances in the photovoltaic efficiencies of PSCs have been achieved in the past few years, research on the stability of PSCs has been relatively less explored. In this study, a new kind of CdS hole-blocking layer replacing the traditional compact TiO2 layer is developed to improve the photostability of PSCs because the intrinsic oxygen vacancies of the TiO2 surface are suspected to be the main cause for the photoinduced degradation of PSCs. As a result, PSCs with the CdS layer exhibit considerably improved photostability, maintaining over 90% of the initial efficiency after continuous sunlight illumination for 12 h, while the TiO2 PSC retains only 18% of the initial efficiency under the same conditions. Charge transfer characteristics related to photodegradation are investigated by various analyses including electrochemical impedance spectroscopy and open-circuit voltage decay and time-resolved photoluminescence decay measurements. the CdS PSC exhibits negligible degradation in the charge-carrier dynamics, while the TiO2 PSC suffers from severely damaged characteristics like increased charge recombination rate, charge-transfer resistance, and reduced charge extraction rate. PMID- 26809353 TI - Gingerol protects against experimental liver fibrosis in rats via suppression of pro-inflammatory and profibrogenic mediators. AB - 6-Gingerol (Gin) is known to possess hepatoprotective effects. Liver fibrosis is a major health concern that results in significant morbidity and mortality. There is no FDA-approved medication for liver fibrosis. The present work aimed at exploring the beneficial effects of Gin against liver fibrosis in rats. Experimental fibrosis was induced by challenging animals with CCl4 for 6 weeks. Gin significantly ameliorated the increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, albumin, total cholesterol (TC) and triglyceride (TG) concentrations, and liver index. These effects were confirmed by light and electron microscopic examinations. The antifibrotic effects were confirmed by examining Masson trichrome-stained liver sections which indicated reduced collagen deposition in Gin-treated animals. Further, Gin administration hampered alpha-smooth muscle actin (alpha-SMA) expression and significantly reduced hepatic content of transforming growth factor-beta (TGF beta). Also, Gin elicited profound antioxidant actions as indicated by preventing reduced glutathione (GSH) depletion and lipid peroxide accumulation. The observed antifibrotic activities involved decreased production of nuclear factor kappaB (NF-kappaB), tumor necrosis factor alpha (TNF-alpha), expression of toll-like receptor 4 (TLR4), intercellular adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM). Involvement of Gin anti-inflammatory activity was verified by the decreased expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in livers of animals treated with Gin. Thus, it can be concluded that Gin protects against CCl4-induced liver fibrosis in rats. This can be ascribed, at least partly, to its antioxidant, anti-inflammatory effects as well as the inhibition of NF-kappaB/TLR-4 expression. PMID- 26809354 TI - Effects of treatment with the anti-parasitic drug diminazene aceturate on antioxidant enzymes in rat liver and kidney. AB - Diminazene aceturate (DA) is the active component of some trypanocidal drugs used for the treatment of animals infected with trypanosomosis and babesiosis. Residues of DA may cause hepatotoxic and nephrotoxic effects. Therefore, the purpose of this study was to investigate the occurrence of oxidative stress, i.e., changes in the antioxidant defense system of rats treated with a single dose of 3.5 mg kg(-1) of DA. All treatments were intramuscularly administered, and evaluations were performed on days 7 and 21 post-treatment (PT). Liver and kidney samples were collected and evaluated by histopathology and oxidative stress parameters (thiobarbituric acid-reactive species, catalase, superoxide dismutase, carbonyl, non-protein thiols, and reduced glutathione). Finally, blood was collected to determine seric DA concentration. Superoxide dismutase (SOD) and catalase (CAT) activities in liver and kidney of rats were dramatically inhibited (p < 0.05) compared to the control group on day 21 PT. This difference is related to the concomitant increase (p < 0.05) in malondialdehyde (MDA) content, which was identified by an increase in thiobarbituric acid-reactive species (TBARS) levels. The carbonyl levels did not differ between groups (p > 0.05). Both non protein thiols (NPSH) and glutathione (GSH) levels in liver and kidney decreased (p < 0.05) on day 21 PT. Chromatographic analyses showed lower levels of DA on day 21 PT compared to day 7 PT. A negative correlation was observed between DA concentration in serum and lipid peroxidation in liver and kidney tissues on 21 days PT. Histopathology revealed vacuolar degeneration in liver and kidney samples on day 21 PT. Our findings indicate that DA could cause oxidative damage to liver and kidney of rats. PMID- 26809355 TI - A systematic review and meta-analysis of clinical and patient-reported outcomes following two procedures for recurrent traumatic anterior instability of the shoulder: Latarjet procedure vs. Bankart repair. AB - BACKGROUND: The Bankart repair and Latarjet procedure are both viable surgical options for recurrent traumatic anterior instability of the shoulder joint. The anatomic repair is the more popular option, with 90% of surgeons internationally choosing the Bankart repair as the initial treatment. There has been no previous review directly comparing the 2 techniques. Hence, we aimed to systematically review studies to compare the outcomes of Bankart repairs vs. the Latarjet procedure for recurrent instability of the shoulder. METHODS: Six electronic databases were searched for original, English-language studies comparing the Bankart and Latarjet procedures. Studies were critically appraised using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Data were extracted from the text, tables, and figures of the selected studies. RESULTS: Eight comparative studies were identified with 795 shoulders; 416 of them underwent open or arthroscopic Bankart repairs, and 379 were repaired by the open Latarjet procedure. Primary and revision procedures were studied. The Latarjet procedure conferred significantly lower risk of recurrence and redislocation. There was no significant difference in the rates of complication requiring reoperation between the two procedures. Rowe scores were higher and loss of external rotation lower in the Latarjet group compared with the Bankart repair group. CONCLUSIONS: Our studies demonstrate that the Latarjet procedure is a viable and possibly superior alternative to the Bankart repair, offering greater stability with no significant increase in complication rate. However, the studies identified were retrospective and of limited quality, and therefore randomized controlled trials with large populations of patients or prospective assessment of national orthopedic registries should be employed to confirm our findings. PMID- 26809356 TI - Construction and Quantitative Validation of Chicken CXCR4 Expression Reporter. AB - Site directional migration is an important biological event and an essential behavior for latent migratory cells. A migratory cell maintains its motility, survival, and proliferation abilities by a network of signaling pathways where CXCR4/SDF signaling route plays crucial role for directed homing of a polarized cell. The chicken embryo due to its specific vasculature modality has been used as a valuable model for organogenesis, migration, cancer, and metastasis. In this research, the regulatory regions of chicken CXCR4 gene have been characterized in a chicken hematopoietic lymphoblast cell line (MSB1). A region extending from 2000 bp upstream of CXCR4 gene to +68 after its transcriptional start site, in addition to two other mutant fragments were constructed and cloned in a promoter less reporter vector. Promoter activity was analyzed by quantitative real-time RT PCR and flow cytometry techniques. Our findings show that the full sequence from 2000 to +68 bp of CXCR4 regulatory region is required for maximum promoter functionality, while the mutant CXCR4 promoter fragments show a partial promoter activity. The chicken CXCR4 promoter validated in this study could be used for characterization of directed migratory cells in chicken development and disease models. PMID- 26809357 TI - SmartSenior@home: Acceptance of an integrated ambient assisted living system. Results of a clinical field trial in 35 households. AB - AIMS: The primary objective of the SmartSenior@home study was to examine the acceptance of the SmartSenior system by older adults. METHODS: Twenty-eight partners from industry and research, including the health care sector, worked collaboratively to implement services aiming to maximize independence in old age. The prospective cohort study was conducted in Potsdam, Germany, with n = 35 older adults between 55 and 88 years of age in their apartments. All participants underwent extensive pre- and post-study visits with in-home interviews, functional assessments for cognition, fine motor skills, and mobility as well as responding to questionnaires on user acceptance and quality of life. RESULTS: The results indicate moderate-to-high user acceptance for the SmartSenior system. In particular, the services for general assistance and health, such as audio/video communication, blood pressure monitoring, and communication with a health professional, were rated as very attractive. Less used and less accepted services were those promoting social interaction and reminder services. CONCLUSION: Besides reliable functioning of the SmartSenior system, the availability of a confidant seems to be the most significant acceptance factor. As one conclusion of this trial, it is possible to develop, integrate, and test an infrastructure for ambient assisted living services in real life. PMID- 26809358 TI - Cerebrovascular reactivity changes in asymptomatic female athletes attributable to high school soccer participation. AB - As participation in women's soccer continues to grow and the longevity of female athletes' careers continues to increase, prevention and care for mTBI in women's soccer has become a major concern for female athletes since the long-term risks associated with a history of mTBI are well documented. Among women's sports, soccer exhibits among the highest concussion rates, on par with those of men's football at the collegiate level. Head impact monitoring technology has revealed that "concussive hits" occurring directly before symptomatic injury are not predictive of mTBI, suggesting that the cumulative effect of repetitive head impacts experienced by collision sport athletes should be assessed. Neuroimaging biomarkers have proven to be valuable in detecting brain changes that occur before neurocognitive symptoms in collision sport athletes. Quantifying the relationship between changes in these biomarkers and head impacts experienced by female soccer athletes may prove valuable to developing preventative measures for mTBI. This study paired functional magnetic resonance imaging with head impact monitoring to track cerebrovascular reactivity changes throughout a season and to test whether the observed changes could be attributed to mechanical loading experienced by female athletes participating in high school soccer. Marked cerebrovascular reactivity changes were observed in female soccer athletes, relative both to non-collision sport control measures and pre-season measures and were localized to fronto-temporal aspects of the brain. These changes persisted 4 5 months after the season ended and recovered by 8 months after the season. Segregation of the total soccer cohort into cumulative loading groups revealed that population-level changes were driven by athletes experiencing high cumulative loads, although athletes experiencing lower cumulative loads still contributed to group changes. The results of this study imply a non-linear relationship between cumulative loading and cerebrovascular changes with a threshold, above which the risk, of injury likely increases significantly. PMID- 26809359 TI - Infective endocarditis: Clinical presentation, etiology, and early predictors of in-hospital case fatality. AB - OBJECTIVE: We aimed to assess the clinical presentation, microbial etiology and outcome of patients presenting with infective endocarditis (IE). PATIENTS AND METHODS: We conducted a four-year retrospective study including all patients presenting with IE. RESULTS: We included 121 patients in the study. The median age was 74.8years. Most patients had native valve IE (57%). Staphylococcus aureus accounted for 24.8% of all IE. Surgery was indicated for 70 patients (57.9%) but actually performed in only 55 (44.7%). Factors associated with surgery were younger age (P=0.002) and prosthetic valve IE (P=0.001). Risk factors associated with in-hospital mortality were diabetes mellitus (OR=3.17), chronic renal insufficiency (OR=6.62), and surgical indication (OR=3.49). Mortality of patients who underwent surgery was one sixth of that of patients with surgical indication who did not have the surgery (P<0.001). PMID- 26809360 TI - Combination of Metal Coordination Tetrahedra and Asymmetric Coordination Geometries of Sb(III) in the Organically Directed Chalcogenidometalates: Structural Diversity and Ion-exchange Properties. AB - Chalcogenidometalates exhibit rich and diverse structures and properties applicable to ion exchange, thermoelectrics, photocatalysis, nonlinear optics, and so on. This personal account summarizes our recent progress in constructing chalcogenidometalates by combining metal coordination tetrahedra and the asymmetric coordination geometries of Sb(3+) in the presence of organic species (typically organic amines and metal-organic amine complexes), which has been demonstrated as an effective strategy for synthesizing chalcogenidometalates with diversified structures and interesting properties. The linkage modes of asymmetric SbQn (n = 3, 4) geometries and group 13 (or 14) metal coordination tetrahedra are analyzed, and the secondary building units (SBUs), with different compositions and architectures, are clarified. The crucial role and function of organic species in the formation of chalcogenidometalates are explored, with an emphasis on their powerful structure-directing features. In particular, some chalcogenidometalates in this family exhibit excellent ion-exchange properties for Cs(+) and/or Sr(2+) ions; the factors affecting ion-exchange properties are discussed to understand the underlying ion-exchange mechanism. PMID- 26809361 TI - Verrucous carcinoma arising in a port wine stain. PMID- 26809362 TI - Type II hereditary angioedema: The first case report in Taiwan. PMID- 26809364 TI - Psychopathological traits in college students from top-ranking french schools: Do autistic features impair success in science when associated with schizotypal traits? AB - The link between personality and the interest of individuals for science has not been thoroughly explored. In this report, we studied psychopathological traits in students studying science in French top-ranking institutions. Three hundred and forty seven individuals answered questionnaires assessing autistic and schizotypal dimensions, as well as anxiety, depression symptomatology and attachment quality. A cluster analysis based on autistic and schizotypal traits led to the identification of 4 distinct profiles: a "low trait cluster", a "moderate autistic trait cluster", a "moderate schizotypal trait cluster" and a "high trait cluster" (HTC) composed of individuals with high scores on both autistic and schizotypal scales. Each cluster represented 20.1-27.1% of participants and was clearly different from the three others, both on autistic and on schizotypal dimensions. These groups could be also typified by their level of anxiety, depression or degraded attachment, which are proportional to the extent of psychopathological traits. Moreover, students from the HTC cluster displayed lower academic results, thus implying that autistic traits might impair success in science when they are associated with moderate schizotypal personality features. This study also suggests that depression and anxiety might mediate performance inhibition in the HTC group. PMID- 26809365 TI - Compulsive buying and depressive symptoms among female citizens of the United Arab Emirates. AB - Compulsive buying is particularly relevant in nations with high levels of consumer spending. Most previous studies have focused on European and North America populations. This study explores compulsive buying amongst citizens of the United Arab Emirates, an Arab nation with high retail outlet density, and high levels of consumer spending. Female college students (N=100) completed an English/Arabic version of the compulsive buying scale along with a measure of depression. Rates of compulsive buying were higher than those reported in any previously published study. Furthermore, in line with previous findings from other nations, compulsive buying was associated with elevated depressive symptomatology. PMID- 26809366 TI - Objective and subjective burden in relatives of patients with schizophrenia and its influence on care relationships in Chile. AB - This study examined the burden on family members of patients with schizophrenia in a Chilean community. Sixty-five caregivers underwent the Subjective and Objective Family Burden Interview. The results showed moderate to high levels of subjective burden and low levels of support from others in providing care. Burden and containment of disturbed behaviour were correlated with worse relationships between patients and caregivers, with the latter spending less time working outside the home. The assessed sample showed a similar pattern of burden to that of caregivers from developed countries; however, the extent of the burden tended to be higher in Chilean caregivers. PMID- 26809367 TI - Validation of the French version of the Acceptability E-scale (AES) for mental E health systems. AB - Despite the increasing use of E-health systems for mental-health organizations, there is a lack of psychometric tools to evaluate their acceptability by patients with mental disorders. Thus, this study aimed to translate and validate a French version of the Acceptability E-scale (AES), a 6-item self-reported questionnaire that evaluates the extent to which patients find E-health systems acceptable. A forward-backward translation of the AES was performed. The psychometric properties of the French AES version, with construct validity, internal structural validity and external validity (Pearson's coefficient between AES scores and depression symptoms on the Beck Depression Inventory II) were analyzed. In a sample of 178 patients (mean age=46.51 years, SD=12.91 years), the validation process revealed satisfactory psychometric properties: factor analysis revealed two factors: "Satisfaction" (3 items) and "Usability" (3 items) and Cronbach's alpha was 0.7. No significant relation was found between AES scores and depression symptoms. The French version of the AES revealed a two-factor scale that differs from the original version. In line with the importance of acceptability in mental health and with a view to E-health systems for patients with mental disorders, the use of the AES in psychiatry may provide important information on acceptability (i.e., satisfaction and usability). PMID- 26809368 TI - Maternal attitudes towards home birth and their effect on birth outcomes in Iceland: A prospective cohort study. AB - OBJECTIVE: to examine the relationship between attitudes towards home birth and birth outcomes, and whether women's attitudes towards birth and intervention affected this relationship. DESIGN: a prospective cohort study. SETTING: the study was set in Iceland, a sparsely populated island with harsh terrain, 325,000 inhabitants, high fertility and home birth rates, and less than 5000 births a year. PARTICIPANTS: a convenience sample of women who attended antenatal care in Icelandic health care centres, participated in the Childbirth and Health Study in 2009-2011, and expressed consistent attitudes towards home birth (n=809). FINDINGS: of the participants, 164 (20.3%) expressed positive attitudes towards choosing home birth and 645 (79.7%) expressed negative attitudes. Women who had a positive attitude towards home birth had significantly more positive attitudes towards birth and more negative attitudes towards intervention than did women who had a negative attitude towards home birth. Of the 340 self-reported low-risk women that answered questionnaires on birth outcomes, 78 (22.9%) had a positive attitude towards home birth and 262 (77.1%) had a negative attitude. Oxytocin augmentation (19.2% (n=15) versus 39.1% (n=100)), epidural analgesia (19.2% (n=15) versus 33.6% (n=88)), and neonatal intensive care unit admission rates (0.0% (n=0) versus 5.0% (n=13)) were significantly lower among women who had a positive attitude towards home birth. Women's attitudes towards birth and intervention affected the relationship between attitudes towards home birth and oxytocin augmentation or epidural analgesia. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: the beneficial effect of planned home birth on maternal outcome in Iceland may depend to some extent on women's attitudes towards birth and intervention. Efforts to de-stigmatise out-of-hospital birth and de-medicalize women's attitudes towards birth might increase women's use of health-appropriate birth services. PMID- 26809369 TI - An agenda for midwifery education: Advancing the state of the world's midwifery. PMID- 26809373 TI - XDR-tuberculosis in France: Community transmission due to non-compliance with isolation precautions. PMID- 26809374 TI - Oral pharmacokinetics of baicalin, wogonoside, oroxylin A 7-O-beta-d-glucuronide and their aglycones from an aqueous extract of Scutellariae Radix in the rat. AB - Scutellariae Radix (SR) has been extensively prescribed in folk medicines due to its notable beneficial activities. The flavonoid glucuronides baicalin (BG), wogonoside (WG), oroxylin A 7-O-beta-d-glucuronide (OG) and their aglycones baicalein, wogonin and oroxylin A, are the main components of the herb. So far, majority of previous studies failed to report the pharmacokinetics and none offered an explanation for the systemic exposures of these six flavonoids when the herbal extract was orally administered. In this study, when a SR extract was orally dosed to rats (800mg/kg, equivalent to BG 324.80, WG 124.00, OG 43.04, baicalein 25.36, wogonin 24.40, and oroxylin A 5.79mg/kg), all six flavonoids were detectable throughout the experimental period (48h) using an LC-MS/MS method with the Cmax and AUC0-48h of the glucuronides 10-130 times that of respective aglycones. As the lowest among the three glucuronides in the herb, OG was the most abundant in vivo, while the systemic exposure of wogonin was the highest amongst the three aglycones. The dose-normalized AUC0-48h descended in orders of OG/oroxylin A, WG/wogonin and BG/baicalein. Two di-conjugates of baicalein (BG glucuronide and BG glucoside), two BG isomers (minor BM1 and major BM2), and one WG isomer (wogonin 5-O-glucuronide) were detected in rat plasma. Semi quantitation of the isomers with peak area data revealed that the AUPs (area under peak area ratio-time curves) of BG isomers were ~3 times that of BG, yet the AUP of wogonin 5-O-glucuronide was only one seventh of WG. BM2, tentatively assigned as baicalein 6-O-glucuronide, was formed from both microbial isomerization of BG and hepatic glucuronidation of baicalein. Wogonin 5-O glucuronide was only formed in hepatic glucuronidation of wogonin. Demethylated wogonin was observed in gut bacteria, offering an optional origin of BM1 apart from baicalein glucuronidation. Microbial isomerization of BG and extensive hepatic glucuronidation of baicalein to form BM2as well as a poorer intestinal permeability of baicalein (Papp*10(-6)cm/s) should account for the lower systemic exposures of BG and baicalein. Faster microbial hydrolysis of WG, high intestinal permeability (Papp*10(-5)cm/s) and less hepatic glucuronidation of wogonin explain the relatively high systemic exposure of wogonin. Sole microbial deglycosylation of OG, high intestinal permeability (Papp*10(-5)cm/s) and extensive hepatic glucuronidation of oroxylin A supported the highest systemic exposure of OG. Taken together, the oral kinetics of six flavonoid glucuronides and aglycones in the SR extract were simultaneously obtained. Microbial conversion, intestinal epithelial permeability and hepatic glucuronidation are determinant factors for their systemic exposures. PMID- 26809375 TI - Characterization of oxygenated metabolites of ginsenoside Rg1 in plasma and urine of rat. AB - This study describes the characterization of oxygenated metabolites of ginsenoside Rg1 in rat urine and plasma. These in vivo metabolites were profiled by using UHPLC-QTOF MS-based method. On the basis of high-resolution MS/MS data, and comparison with chemically synthesized authentic compounds, nine oxygenated metabolites of Rg1 were characterized as vinaginsenosides 21 and 22 (M1 and M2), vinaginsenoside R15 (M3), 6-O-(beta-d-glucopyranosyl)-20-O-(beta-d glucopyranosyl) 3beta, 6alpha, 12beta, 20(S)-tetrahydroxy-24xi-hydroxydammar-25 ene (M4 and M5), floralginsenoside A (M7 and M8), floralginsenoside B (M9) and epoxyginsenoside Rg1 (M13), respectively. Among these metabolites, M4, M5 and M13 are new ginsenosides and others were detected as in vivo metabolites of Rg1 for the first time. In addition, a series of oxygenated metabolites of Rh1 and deglycosylated metabolite of Rg1, were observed and characterized by comparing with compounds synthesized by us, which revealed an association between C-20 configuration and the extent of oxidation metabolism. Appearance of all these metabolites in blood stream and urine after i.v. dosing and oral administration of Rg1 was further examined, which clearly showed that mono-oxygenated metabolites of Rg1 were major circulating metabolites at the early stage after dosing. Characterization of exact chemical structures of these circulating metabolites contribute greatly to our understanding of chemical exposure after consumption of ginseng products, and provide valuable information for explaining multiple bioactivities of ginseng products. PMID- 26809376 TI - Comparison of antioxidant and antiproliferative activity between Kunlun Chrysanthemum flowers polysaccharides (KCCP) and fraction PII separated by column chromatography. AB - The aim of the present study was to compare the antioxidant and antiproliferative effects on cancer cells between Kunlun Chrysanthemum flowers polysaccharides (KCCP) and its fraction PII that were separated by Biologic low pressure (LP) chromatography system followed by DEAE cellulose column chromatography. Results of in vitro experiments showed that the reducing power and the scavenging capacity of KCCP towards hydroxyl radicals (OH) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals increased in a concentration dependent manner and were stronger than that of fraction PII. Results of the antiproliferative effect of KCCP and fraction PII on cervical cancer HeLa cells, esophagus cancer Eca109 cells, and mouse ascites hepatomas H22 cells indicated that both KCCP and its fraction PII possessed inhibitory activity on all the tested cancer cells at a dose- and time dependent manner, with KCCP showing higher inhibitory activity than that of fraction PII. The present study demonstrates that KCCP and its fraction PII have antioxidant properties that may help fight cancers. PMID- 26809377 TI - Involvement of intracellular cAMP in epirubicin-induced vascular endothelial cell injury. AB - We investigated the involvement of intracellular cAMP in endothelial cell injury induced by epirubicin. Epirubicin-induced decrease in cell viability and increase in caspase-3/7 activity were reversed by a cAMP analog dibutyryl cAMP (DBcAMP) or an activator of adenylate cyclase forskolin concomitant with a phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Moreover, epirubicin-induced elevation of lipid peroxide levels was attenuated by DBcAMP. Interestingly, the exposure of epirubicin decreased intracellular cAMP levels before the onset of epirubicin induced production of lipid peroxidation. These results suggest that intracellular cAMP plays an important role in epirubicin-induced endothelial cell injury. PMID- 26809378 TI - Describing the role of Australian community pharmacists in oral healthcare. AB - OBJECTIVES: To investigate community pharmacist's attitudes, beliefs and practices towards oral health in the Australian setting, describe the frequency and nature of consumer enquiries relating to oral health, and gain insight regarding smoking cessation support for people experiencing oral health problems. METHODS: An online questionnaire was developed based on previous research, validated to ensure accuracy and reliability, and convenience sampling used to advertise across major pharmacy organisational websites and newsletters to maximise community pharmacist responses. KEY FINDINGS: One hundred and forty-four valid community pharmacist responses were descriptively analysed. The majority of pharmacists (93%) believed it was their role to deliver oral health advice in the community and almost all (97%) pharmacists believed further education would benefit their practice. The top four consumer enquiries pharmacists reported confidence in handling related to analgesic medication to relieve oral-related pain (95.8%), mouth ulcers (95.1%), oral thrush (94.4%) and toothache (93.8%); and the most frequently reported consumer enquires were those where the majority of pharmacists reported high confidence in handling. A small proportion of pharmacists (8%) always enquired about patient smoking status, and nearly all pharmacists (97%) desired further education and training to benefit their practice in oral healthcare. CONCLUSION: This study highlights that Australian pharmacists have an important role in oral health and there is opportunity to enhance this role, and address risk factors such as smoking with further training, support and education. The findings from this study can guide future research into the development of appropriate training programmes, standards, and best oral healthcare practices for Australian pharmacists. PMID- 26809379 TI - An Anthocyanin-Rich Extract of Acai (Euterpe precatoria Mart.) Increases Stress Resistance and Retards Aging-Related Markers in Caenorhabditis elegans. AB - Acai fruits (Euterpe precatoria) are rich in antioxidant anthocyanins. Acai consumption is believed to have many health benefits; however, relevant detailed scientific investigations are limited. The current study aimed to investigate an anthocyanin-rich extract from E. precatoria fruits (AE) with regard to its antioxidant and antiaging properties using the model organism Caenorhabditis elegans. AE can protect the worms against oxidative stress and can ameliorate accumulation of reactive oxygen species in vivo. The expression of stress response genes, such as sod-3::GFP, was upregulated while hsp-16::GFP was down regulated after AE treatment. Studies with DAF-16/FOXO mutants indicated that some of the antioxidant effects are mediated by this transcription factor. AE can modulate the development of age-related markers, such as pharyngeal pumping. Despite the apparent antioxidant activity, no lifespan-prolonging effect was observed. PMID- 26809380 TI - Hypertrophic lichen planus - successful treatment with acitretin. AB - Lichen planus classifies into different subtypes according to morphology and location. Hypertrophic LP (HLP) manifests a great challenge due to persistent itching, the risk to develop into squamous cell carcinoma and therapeutic resistance. We report two clinical cases exemplary for the successful treatment of dramatic-resistant HLP with acitretin. PMID- 26809382 TI - Percutaneous Decompression of the Left Ventricle in Cardiogenic Shock Patients on Venoarterial Extracorporeal Membrane Oxygenation. AB - OBJECTIVE: Extracorporeal membrane oxygenation is an important therapeutic option for patients with refractory cardiogenic shock. Adequate decompression of the left ventricular in these patients is a key predictor of successful recovery. The currently available percutaneous decompression techniques are limited by their partial unloading capability. METHOD: We describe a series of four consecutive patients with refractory cardiogenic shock in whom adequate left ventricular decompression was achieved by integrating a transseptally placed left ventricular cannula into the existing extracorporeal membrane oxygenation circuit. RESULTS: From May to June 2015, four consecutive patients underwent transvenous transseptal left ventricular decompression with a 22 French cannula that was integrated into the extracorporeal membrane oxygenation circuit in a Y fashion. The mean age was 47.5 +/- 20 years. All patients had refractory shock, and three patients failed prior decompression with an intra-aortic balloon pump. Fluoroscopy time was 12.15 +/- 2.6 minutes. No procedural complications were noted. All patients had significant reduction in their pulmonary capillary wedge pressure and resolution of their pulmonary edema. Two patients died during the hospitalization due to sepsis and/or multiorgan failure. CONCLUSION: Antegrade transseptal left ventricular decompression is feasible in patients on extracorporeal membrane oxygenation and persistent pulmonary edema. PMID- 26809384 TI - Gini index estimation for lifetime data. AB - Lifetime data is often right-censored. Recent literature on the Gini index estimation with censored data focuses on independent censoring. However, the censoring mechanism is likely to be dependent censoring in practice. This paper proposes two estimators of the Gini index under independent censoring and covariate-dependent censoring, respectively. The proposed estimators are consistent and asymptotically normal. We also evaluate the performance of our estimators in finite samples through Monte Carlo simulations. Finally, the proposed methods are applied to real data. PMID- 26809385 TI - Selective microwave sensors exploiting the interaction of analytes with trap states in TiO2 nanotube arrays. AB - Sensing of molecular analytes by probing the effects of their interaction with microwaves is emerging as a cheap, compact, label-free and highly sensitive detection and quantification technique. Microstrip ring-type resonators are particularly favored for this purpose due to their planar sensing geometry, electromagnetic field enhancements in the coupling gap and compatibility with established printed circuit board manufacturing. However, the lack of selectivity in what is essentially a permittivity-sensing method is an impediment to wider adoption and implementation of this sensing platform. By placing a polycrystalline anatase-phase TiO2 nanotube membrane in the coupling gap of a microwave resonator, we engineer selectivity for the detection and differentiation of methanol, ethanol and 2-propanol. The scavenging of reactive trapped holes by aliphatic alcohols adsorbed on TiO2 is responsible for the alcohol-specific detection while the different short chain alcohols are distinguished on the basis of differences in their microwave response. Electrodeless microwave sensors which allow spectral and time-dependent monitoring of the resonance frequency and quality factor provide a wealth of information in comparison with electrode-based resistive sensors for the detection of volatile organic compounds. A high dynamic range (400 ppm-10,000 ppm) is demonstrated for methanol detection. PMID- 26809386 TI - Characterization of tight junction disruption and immune response modulation in a miniaturized Caco-2/U937 coculture-based in vitro model of the human intestinal barrier. AB - A microfluidic-based dynamic in vitro model of the human intestinal barrier has been constructed and characterized. The intestinal epithelial monolayer was mimicked by culturing caco-2 cells on a porous membrane in a double-layered microfluidic chip and interfaced with a co-culture of U937 as a model of immune responsive cells. The physiological flow was also mimicked by a continuous perfusion of culture media from the apical and basolateral side of the porous membrane. This dynamic "in vivo-like" environment maintains a continuous supply of cell nutrient and waste removal and create mechanical shear stress within the physiological ranges which promotes uniform cell growth and tight junction formation. The monolayer permeability to soluble ion changes after treating with LPS, and TNF alpha as indicated by the reduction of the TEER value. In addition, the immune competent caco-2/U937-based model allowed the investigating the role of the epithelial layer as a protection barrier to biological hazards as indicated by the suppressing of the pro-inflammatory cytokine expression. PMID- 26809387 TI - Early National Experience with Laparoscopic Pancreaticoduodenectomy for Ductal Adenocarcinoma: Is This Really a Short Learning Curve? PMID- 26809388 TI - The Learning Curve Is Surmountable: In Reply to Fong and colleagues. PMID- 26809389 TI - Should We Remove Divided Hepatic Venous Territory Retaining Portal Flow? PMID- 26809390 TI - Preserving Liver Function: In Reply to Kawaguchi and colleagues. PMID- 26809391 TI - A True Deficit in Surgeons' Knowledge of Costs: In Reply to Dempsey and colleagues. PMID- 26809392 TI - Correcting Surgeons' Knowledge Deficit. PMID- 26809394 TI - [The Home Care Doctor Today is "STRIKE" - Considering Care of Terminal Stage Patients with Cancer through a Case Report]. AB - Although many patients wish to remain in their familiar home environment while undergoing cancer treatment, many obstacles prevent a patient from receiving cancer care at home. With early-stage cancer, the patients may better accept the diagnosis and have a greater will to fight the illness. However as time proceeds, progression or recurrence of cancer may occur, and eventually, proactive treatments will not be available. This progression results in great physical and mental strain on the patients and their family. At all stages of such progression, opportunities exist for a care provider to assist with overcoming potential obstacles by openly communicating with the patients, talking through the patients' experiences, and understanding their feelings. However, on diagnosis, cancer patients must often face the reality that they have very little time left to live. When transiting medical care from their long-trusted hospital to a home care base, a new physician must be selected and other decisions related to their care must be quickly made. Transferring responsibility to a good home care provider can greatly influence a patient's emotional state. This paper reports one such case in which the patients died in their homes with the best comfort and possible outcome. PMID- 26809395 TI - [Strengthening Cooperation between Medical and Nursing Care - A Collaborative Meeting of Home Care Doctors and Care Managers in Shinjuku-City]. AB - The number of elderly patients requiring home care is expected to increase as a result of the aging population and a decrease in the average length of hospital stay in Shinjuku Ward. Therefore, cooperation between medical and nursing staff is increasingly important. According to research on care managers conducted by Shinjuku Ward, care managers have little opportunity to discuss plans of care with doctors, which requires improvement. In order to strengthen the cooperation between medical and nursing staff, Shinjuku Ward conducted a collaborative meeting for home care doctors and care managers. In the results of the questionnaire given to participants, all respondents answered"Helpful"when asked if the meeting was useful, and 95% of respondents indicated that"understanding and perspective of each other's area has deepened."Therefore, additional collaborative meetings were suggested to promote cooperation and mutual understanding between doctors and care managers. PMID- 26809396 TI - [The Present Conditions of a Provincial City]. AB - The goal of community-based comprehensive care is to improve the quality of life(QOL)of patients by accommodating their individual values and by making full use of inter-professional collaboration. Since the number of individuals over the age of 65 years in provincial cities has already reached its peak, any future increase in the number of individuals over the age of 65 years will be due to a decrease in the working-age population. As there is no time to spare, immediate actions must be taken to promote collaboration among nursing and welfare facilities. To ensure an accurate understanding and awareness of home care, we have launched in-home treatment support services in a general hospital with the aim of enriching home care and facilitating smooth transitions to in-home treatment. Each community should discuss appropriate measures that will foster the growth of home care services and help individual patients live independent, comfortable lives. PMID- 26809397 TI - [The Current Status of Palliative Care for Patients with Advanced Cancer in Nishinomiya City]. AB - It is very important for advanced cancer patients who receive palliative care to select appropriate places to stay during the end-of-life period. We reviewed the cases of 147 patients who were referred to palliative care services from our hospital. Forty-four patients(30%)were referred to palliative care facilities, and 103 patients(70%)received palliative care in their homes. Fifty-two patients(47%)died at a palliative care facility, 41(37%)died at home, and 18(16%)died at our hospital. The proportion of patients who died at home was three times the number of people who wanted to die at home, according to a Japan National questionnaire. To increase cooperation between regional hospitals and home palliative care services, we attended meetings and conferences conducted by the Nishinomiya City Medical Association. As a result of these activities, we think that the number of patients who die at home has increased. PMID- 26809398 TI - [Utility of Smartphone in Home Care Medicine - First Trial]. AB - The use of video calls for home care can reduce anxiety and offer patients peace of mind. The most suitable terminals at facilities to support home care have been iPad Air and iPhone with FaceTime software. However, usage has been limited to specific terminals. In order to eliminate the need for special terminals and software, we have developed a program that has been customized to meet the needs of facilities using Web Real Time Communication(WebRTC)in cooperation with the University of Aizu. With this software, video calls can accommodate the large number of home care patients. PMID- 26809399 TI - [Examination of the Application of and Issues with Mobile Testing Equipment in Examples of Utilization in Home Care Support Clinics]. AB - The number of patients requiring testing in the future is expected to increase further with an increase in the number of home care patients that are highly dependent on medical care and in the process of developing health care policies that aim at the creation of regional-based total medical care. The effective use of new technologies to support patients is examined to avoid the fact that fluctuations in patients' health and the limitations of caregivers' capacity make it difficult to continue home care. This study focuses on mobile testing equipment and aims to clarify test applications using this equipment, as well as issues during applications. Interviews were conducted with four physicians that have actual experience in using mobile testing equipment at home care support clinics, and a qualitative analysis was carried out. As a result, seven categories for test applications and five categories for issues were identified. The current state of and new approaches for home care were inferred using evidence from those categories. PMID- 26809400 TI - [Effects of Instruction on Inhalation Techniques Using iPads - Web Application "Inhalation Lessons"]. AB - Instruction on inhalation techniques for chronic obstructive pulmonary disease(COPD)and asthma patients being treated with inhalants have sufficient therapeutic effects and are important to maintain adherence. However, problems continue to exist, including time constraints of medical staff that have a large number of patients and a lack of knowledge on inhalation instruction methods. A web application,"Inhalation Lessons,'for the iPad has been developed. It explains inhalation methods, and consists of videos and review tests. Instruction on inhalation techniques was performed using this application for patients that use Diskus, and the effects were examined. As a result, there are significant improvements in the inhalation techniques of patients after viewing the"Inhalation Lessons'application. Uniform instruction on inhalation techniques can be performed even in the field of homecare. PMID- 26809401 TI - [Rapid Delivery of Pharmaceutical Drugs in Home Medical Care]. AB - The population of individuals over age 65 has grown in recent years, leading to a revision of the way medical care is provided, including an increased use of home care services, for example. Medicines are delivered to home care patients in accordance with a specific schedule and based on prescriptions written by home care doctors. Although this system functions perfectly well when the patient's condition is stable, a rapidly worsening condition may lead to changes or additions to the list of prescriptions. Moreover, in addition to specialized check-ups by home care doctors, patients may also visit ophthalmologists, orthopedic specialists, or dermatologists on an outpatient basis. In such cases, the provision of drugs often does not follow a regular schedule and may require special delivery to the patients' homes. These types of alterations to medications often happen suddenly and may require drug delivery outside the pharmacies' normal hours of operation, thus imposing a great burden on them. This report aims to describe the realities faced by pharmacies as they attempt to accommodate these sudden demands for drug delivery. PMID- 26809402 TI - [Provision System of Medical Narcotics]. AB - Patients with cancer are increasingly opting for home health care, resulting in a rapid increase in the number of prescriptions for narcotics aimed at pain control. As these narcotics are issued by pharmacies only upon presentation of valid prescriptions, the quantity stored in the pharmacies is of importance. Although many pharmaceutical outlets are certified for retail sale of narcotic drugs, the available stock is often extremely limited in variety and quantity. Affiliated stores of wholesale(or central wholesale)dealers do not always have the necessary certifications to provide medical narcotics. Invariably, the quantity stored by individual branches or sales offices is also limited. Hence, it may prove difficult to urgently secure the necessary and appropriate drugs according to prescription in certain areas of the community. This report discusses the problems faced by wholesalers and pharmacies during acquisition, storage, supply, and issue of prescription opioids from a stockpiling perspective. PMID- 26809403 TI - [Significance of the Pharmacist in Inter-Professional Cooperation]. AB - Two points are considered effective in preventing the exhaustion of the various medical professions involved in home care as we look at the challenges to be confronted in 2025: increasing participation parameters and streamlining business operations. In order to increase participation parameters, the number of participating professions must be increased and the base of existing professional staff must be broadened.In order to streamline business operations, it has been determined that it is important to better understand the functions of each profession and accurately and speedily promote the contents of business operations with staffing that places the right people in the right job.The results of this verification concluded that it is efficient for various professions to each take on roles in their specialties in order to support home care in the community, and to train young people in line with the concept of the Learning Pyramid, with each profession incorporating better functional differentiation and a mentor system, in order to broaden the base of staff.The results also concluded that it is effective to promote information sharing among areas, job types, and related professions. PMID- 26809404 TI - [Challenges Associated with Involvement of Small-Scale Pharmacies in Home Health Care]. AB - As our society is progressing towards a composition wherein a significant portion is constituted by the elderly, a comprehensive home health care system is warranted. The provision of pharmacy services is a key factor in ensuring comprehensive home health care. Our pharmacy has been involved in home health care since its inception. This report is an attempt at evaluation of future prospects through identification and analysis of current operational issues. Our pharmacy is adequately equipped to accommodate home cared patients with significant medical dependency. However, being a small-scale business with few employees, coordinating shifts to ensure 24 hours operation in addition to providing home visits when required has been challenging. These place a substantial burden on the staff pharmacists. It is highly challenging for a single small-scale pharmacy to operate as a"self-contained pharmacy"that remains independent and still adequately serves their clients. Creating a collaborative pharmaceutical service team, consisting of several complementary small-scale pharmacies, provisionally called a "regional cooperative pharmacy,"could prove to be a more realistic alternative. In the coming decade, improving the implementation of home health care through regional level cooperation is necessary. This would require the collaboration various professionals, and the involvement of municipalities and professional organizations to ensure adequate regional support services. PMID- 26809405 TI - [A Way of Medication Support for Elderly People Who are Solitary and Have Declined Cognitiveability]. AB - Home-based medical care has been promoted in recent times because of a decline in the birthrate and increased elderly population, and there is wide individual variation in the elderly patients' recuperating environment and/or symptoms. In our experience, when solitude and dementia overlap, patient-management becomes challenging. In the management of such patients, we have identified the importance of a pharmacist as part of the home-based medical care team. The pharmacist plays an important role in providing optimal solutions in terms of environmental adjustment for medication/medication support plan, according to the physical ability and cognitive ability of the patient, under a limited care plan. The statistical data from the national database indicates that there will be an increase in the number of elderly people who are "solitary" and have "declined cognitive ability", and this could be a challenge which could be tackled with home-based medical care system. PMID- 26809406 TI - [Case Study - A Successful Outpatient Design of Cross-Professional Pharmaceutical Cooperation in Home Health Care - Reduction of Financial and Care-Related Burden by Shifting to R-Compound Enteral Semisolid Formulation]. AB - Among patients who receive enteral nutrition through a gastric fistula, some are concomitantly administered viscosity modifiers to avoid aspiration pneumonitis caused by gastroesophageal reflux. These patients(and families)often bear the high economic and care burdens associated with enteral nutritional management. We developed an outpatient-based pharmacy service through multidisciplinary cooperation, facilitating a shift from enteral nutrition to semi-solid formula. This shift is expected to reduce the economic burden by approximately 120 thousand yen, and the hours of care by about 550 hours annually. Owing to family circumstances or economic conditions, some patients(and families)do not receive at-home guidance of pharmaceutical management by pharmacists. The family members of such patients visit the pharmacy to obtain the prescribed medications. Such patients and families could be supported within the outpatient-based pharmacy services, through proactively participating in home health care daily(collaborative relationship with the local community)and re-counting experiences of providing home guidance of pharmaceutical management. PMID- 26809407 TI - [Reality of Inter-Professional Cooperation in Medical Day Care Facilities - What is Visible from the Level of Inter-Professional Cooperation]. AB - In order to improve the quality of life of patients with moderate to severe symptoms who are highly dependent on medical care and to reduce the physical and psychological burden on family members, at medical day care facilities, care and services, such as functional training, is provided to improve daily life for patients in need of significant care who have intractable diseases under the Long Term Care Insurance Act; home care patients, such as those in the final stages of cancer; and severely mentally and physically handicapped children under the Child Welfare Act. This study conducted semi-structured interviews with 15 nurses working in medical day care facilities with the objective of clarifying the reality of inter-professional cooperation of nurses working in these facilities and contributing to delivery of high-quality care. The results of the study revealed that the level of inter-professional cooperation of nurses at medical day care facilities was high and that professions that are involved in cooperation include visiting nurses, doctors, medical staff, such as physical therapists, caregivers, and welfare professions, such as care managers. The study also showed that the contents of cooperation include information exchange, information sharing, continuation of care, implementation of care that respects the intentions of the patient, care proposals, and guidance and control regarding care. PMID- 26809408 TI - [The Current State of Inappropriate Drug Use among Elderly Assisted-Living Residents]. AB - Previous studies have reported that elderly assisted-living residents use multiple drug combinations and inappropriate drugs.The aim of this study was to assess the drug use and its consequences in residents of a nursing facility.We examined the prescriptions of all residents in a nursing facility in Osaka from their medical records.Of the total 67 residents, 48 were women.The average age of the residents was 86 years, the average number of prescription drugs they took was 6.4, and the average number of diseases present was 4.9. Correlation between the number of diseases and the drugs taken was significant (p<0.05), but the correlation between the degree of independence for activities of daily living and the number of the drugs taken was not significant.The most commonly present health condition was bone fracture.About 50% of the residents used a psychotropic drug and prescription drugs such as amantadine and hydroxyzine, which are not advisable for elderly people.It is necessary for the elderly to avoid the use of drugs that cause delirium and drowsiness, and future studies should focus on methods to prevent disuse syndrome in the elderly. PMID- 26809409 TI - [Local Control with At-Home Mohs Paste Treatment for Malignant Tumor Exposed at the Skin]. AB - Malignant tumors exposed at the body surface are often complicated by bleeding, effusion, infection, and offensive odor, which can lead to impairment of patients' QOL. Mohs paste has previously been used in the treatment of cutaneous malignant tumors as a local application for such symptoms during palliative care; some reports indicate that this procedure is effective. However, most of the cases were treated in hospital. We have performed this procedure as a part of home care. From January 2011 to December 2014, we studied Mohs paste treatment at home in 5 patients. In all cases, hemostasis and reduction of effusion were observed. To ensure a safe procedure, the patient is required to maintain the rest position during the treatment. We conclude that Mohs paste treatment is possible at home and that this procedure is an effective means to support the patients hoping for home care. PMID- 26809410 TI - [Clinical Utility of Tapentadol]. AB - Tapentadol(TP)is a new strong opioid analgesicthat has both m-opioid receptor(MOR)effects and norepinephrine reuptake inhibitor(NRI)effects. In comparison with the existing strong opioid analgesics, the mechanism of action suitable for palliation of neuropathic pain is expected to be better for TP. The analgesic effect and side effects of this drug were tested in 10 cases of exacerbation of neuropathic pain at our hospital, and the sedative response rate was 70%. The main side effects were somnolence 44.4%, nausea 33.4%, and constipation 11.1%. The side effects on the digestive system were considered minimal. Although it is speculated that opioids would be useful as an outpatient treatment, few case reports are available regarding their use for cancer pain; therefore, further investigation is necessary. Generally, numerous social issues that would increase the likelihood of drug adherence failure must be addressed in order to expand the use of strong opioid analgesics such as TP. Both the patients and the healthcare worker should be involved when addressing these issues in Japan, and the measures should include instructions for appropriate reporting and for using such drugs. PMID- 26809411 TI - [Cancer Notification by Hospital Doctors for Terminally-Ill Cancer Patients Referred to Visiting Physician]. AB - Notification of cancer is essential for medical treatment based on patient preference. I studied 45 terminally-ill cancer patients referred to my clinic from January 2012 to December 2013. The data of each patient was retrospectively collected from their medical record. Cancer notification was not done in 4 cases(9%). Notification of cancer metastasis or terminally ill status was not done in 9 cases(20%). The reasons for no announcement of cancer included the family's concern regarding depriving the patient or hope or hospital doctor policy. In home-care situations, cancer notification might be difficult because home-care physicians take over patient care from hospital doctors who may not always inform the patient regarding their cancer status. PMID- 26809412 TI - [Our Experience of Providing Home End-of-Life Care for a Child with a Brain Tumor - Overview of Issues Including Environmental Adjustment and Family Care]. AB - INTRODUCTION: We provided home end-of-life care to a child with a brain tumor. As cases of children with malignancies who receive such care have rarely been described in Japan, we report our experience with this patient. CASE REPORT: An 11-year-old previously healthy boy was found to have a brainstem glioma in December X. The tumor was reduced by radiotherapy and chemotherapy, but relapse was noted in August X plus 1. Best supportive care alone was selected for this patient. Before the initiation of home care, we consulted a designated hospital for pediatric cancer treatment in the area and requested a case- worker from the child/home section in his resident area. As the patient was too young for long term care insurance, we immediately applied for a physical disability certificate to augment welfare support. After the initiation of home care, swallowing function diminished markedly, but we provided guidance on dietary contents and suction, allowing continued oral ingestion by prioritizing his and his family's wishes. In January X plus 2 of the following year, his respiratory condition worsened after the development of aspiration pneumonitis, and he died at home. SUMMARY: We advocate the establishment of a regional network so that children with brain tumors can receive end-of-life care at home. PMID- 26809413 TI - [Choice of Expiration for Cancer Patients under Home Medical Care - Palliative Care Unit or Home]. AB - Kohka Public Hospital(KPH)was rebuilt at a new place in April 2013. The Palliative Care Unit(PCU)was newly constructed during renovation. We examined the will and outcome of cancer patients, especially on expiration. A 123 patients died in 2014: 27 died at the PCU, and the remaining 7 at home. Of 27 patients, 20 were willing to die at the PCU, and one patient visited the hospital after judgment by the Visiting Nurse Center. Other 6 patients were admitted finally after their families experienced fatigue. Six of seven patients who died at home, showed a strong will to stay at home. We think that patients' will drives the clinical course, especially in their end-stage. In this context, the majority of the patients decided their terminal place based on their will. On the contrary, there were several cases whose requests were not fulfilled. To overcome the problem, we should discuss cancer patients' will to make a choice regarding death at the end-stage of their lives and the place of expiration in advance. We including the staff of social care and regional medical resources, should co operate and share information on these patients to solve the problems. PMID- 26809414 TI - [End-of-Life Home Care for a Young Patient]. AB - We report the case of a young patient(under 40 years)with a malignant tumor; this is an age when a person is involved in social activity and is productive. A variety of activity largely has a negative influence on family at death of such a patient. After fighting this illness for a long time, home medical care was administered, and I experienced a case of a 31-year-old patient with malignant melanoma who was administered end-of-life home care. He had a diagnosis of right leg malignant melanoma approximately 5 years ago. Palliative medical care was decided, after aggressive treatment for approximately 5 years, including an operation, and home medical care was hoped, after this was introduced at our department of surgery. I performed pain control in this patient after hospitalization at approximately one week and the patient was shifted to home medical care. The patient could only swallow water, and oral medication could not be ingested because the patient was bedridden. The mother who was the main caregiver quit her work and devoted herself for care. I performed pain control mainly by administering oxycodone and a steroid and an anti-inflammatory, which were given intravenously along with the antianxiety drug. During home medical care, I focused on pain control, but the patient expressed gratitude for the main caregiver that was witnessed by the family. The patient died 26 days after the initiation of at-home care. Nursing care insurance is not available for young patients, and home help is limited. I quit work for the caregiver, and including contrivance of the future life, there is much limitation with the aspect of the income. A younger patient experiences temper, as well as physical pain, enough for mental and social pain is necessary. PMID- 26809415 TI - [Three Elderly Female Patients Who Experienced Self-Recovery during End-of-Life Care at Home]. AB - Recently, after completing hospital treatment, 3 elderly female patients were introduced to our home care department for end-of-life care at home. However, these patients recovered almost by themselves and now spend quiet days. From now on, women became the era they live alone in the statistics on the elderly. On the basis of these 3 cases, it is suggested that elderly female patients have the capacity to overcome conditions such as infectious diseases and digestive system disorders. PMID- 26809416 TI - [Skin Care to Prevent Development of Pressure Ulcers in Bedridden Nursing Home Residents from Developing Pressure Ulcers in Nursing Home Residents]. AB - The purpose of this study was to clarify whether skincare products are effective in preventing development of pressure ulcers in bedridden nursing home residents. The study sample consisted of 21 nursing home residents at a nursing home in Osaka, Japan who use diapers. Participants were assigned to 3 groups and compared to a control group. None of the subjects developed a pressure ulcer and had improved skin condition around the anus. PMID- 26809417 TI - [The Role of Certified Nurse in Palliative Care to Promote the Discharge Support and Regional Cooperation for Cancer Patients]. AB - The objective of this study is to understand the issues and solutions considered by certified nurses(CN)in palliative care (hereinafter referred to as"palliative care CN)regarding discharge support and regional cooperation for cancer patients, and to discover the roles and responsibilities of palliative care CN. Data obtained from training sessions for 22 palliative care CNs was reconfigured and analyzed. As a result, problems related to discharge support and regional cooperation for cancer patients were classified into 13 categories and 3 core categories. The following roles for palliative care CN were proposed to promote discharge support and regional cooperation for cancer patients: (1) Inter professional sharing of knowledge about patients and their families to reconcile the intentions of the patient and family members with predictions of progression of the illness; (2) Enable hospital nurses to obtain information about patients after discharge in order to establish a clear image for medical treatment; and(3) Support for ward nurses regarding cooperation to alleviate symptoms and offer medical care to patients who are highly dependent on medical care, and to become a point of contact for cooperation with visiting nurses. PMID- 26809418 TI - [Effect of a Discharge Planning Educational Program in a University Hospital]. AB - The purpose of this study was to investigate the effect of a discharge planning educational program on multidisciplinary team staff in a community. We provided training to nurses of a university hospital. The training covered an introduction to discharge planning, decision-making support, home care medicine and home nursing care, the medical social welfare system, and case review meetings. It was conducted every year from September through February between 2012 and 2015. Before and after the training, the awareness of nurses was evaluated by using self-administered questionnaires and the Discharge Planning scale for Ward Nurses(DPWN), and discharge planning satisfaction was measured using a visual analogue scale (VAS). The study process was reviewed and approved by the Ethics Committee of Tokyo Women's Medical University. The questionnaires were distributed to 96 nurses; of these, responses of 72 nurses(pre- and post training)were analyzed(response rate: 75.0%). The average number of years of nursing experience was 8.5+/- 7.7. The total score of the DPWN and its subscales, as well as the VAS, with regard to satisfaction level significantly increased after the training(p<0.01), indicating that training improved nurses' awareness of discharge planning practices. PMID- 26809419 TI - [Two Cases of Bowel Perforation during Chemotherapy with Bevacizumab to Metastatic Rectal Cancer]. AB - Case 1: A male patient in his 60's who had rectal cancer and liver metastases underwent Hartmann's operation in January 2009. In April 2009, he received chemotherapy with modified FOLFOX6 plus bevacizumab as second-line treatment. Thirteen days later, he complained of abdominal pain and visited the emergency department. Computed tomography(CT)revealed gastrointestinal tract perforation. He underwent emergency surgery. However, dirty brownish ascites was observed, and the perforation point of the gastrointestinal tract could not be found. We suspected perforation of the colon and created an artificial anus in the terminal ileum. After the surgery, his condition improved. Case 2: A male patient in his 60's who had rectal cancer underwent Miles' operation in March 2005. In February 2010, CT revealed local recurrence in the presacral region. After radiotherapy, he received chemotherapy with CapeOX plus bevacizumab. During the course of the chemotherapy, he was admitted for upper abdominal pain and fever. He was diagnosed with a perforation of the transverse colon and underwent emergency surgery. After the surgery, drainage was needed for peritonitis, for about 1 month. At 93 days after the surgery, he was discharged. Gastrointestinal tract perforation is one of the most serious adverse events associated with bevacizumab. To avoid death caused by serious adverse events, medical staff and patient orientation or education on the possible serious adverse event is very important. PMID- 26809420 TI - [Investigation of the Safety of and Patient Satisfaction with iEat(r), the Support Food for the Recovery of Eating Function in Patients with Carcinomatosis Related Gastrointestinal Passage Disorder]. AB - OBJECTIVE: iEat(r), a support food for the recovery of eating function, is food that can be easily masticated with little power and has suitable fluidity for enzyme processing, regardless of its normal appearance. We provided iEat(r) to 5 patients with carcinomatosis-related gastrointestinal passage disorder who could take fluid foods and investigated the stability of iEat(r) and patient satisfaction with the food. METHODS: We provided regular diets for lunch on the first and 7th day, and provided iEat(r) from the 2nd to the 6th day. The stability of iEat(R) was evaluated based on the presence and grade of abdominal pain, diarrhea, sense of abdominal distension, nausea, and vomiting, according to the Common Terminology Criteria for Adverse Events (CTCAE v4.0, JCOG). The patients assessed their satisfaction by using 6 grades of taste, appearance, amount, difficulty of intake, and overall valuation. RESULTS: One patient could not continue the study because of vomiting from overeating of iEat(R). In the other patients, iEat(R) induced approximately the same adverse events as did the regular diets. All of the patients expressed better satisfaction with iEat(r) than with the regular diets. CONCLUSION: Although patient management for overeating is necessary, iEat(r) might provide good quality of life in terms of eating satisfaction to the patients with carcinomatosis-related gastrointestinal passage disorder. PMID- 26809421 TI - Right-to-left shunt through patent foramen ovale during off-pump coronary artery bypass. PMID- 26809422 TI - Transition to practice, lessons learned: Academic general thoracic surgery. PMID- 26809423 TI - Rethinking the gold standard for correction of paravalvular leak. PMID- 26809424 TI - FFR 4 CABG: More than a vanity plate. PMID- 26809425 TI - Options for arterial cannulation to provide antegrade cerebral perfusion: Everything old is new again. PMID- 26809426 TI - Hybrid coronary revascularization: Ready for prime time, but who should star? PMID- 26809427 TI - Identification of novel Syk-independent functional roles of FcgammaRIIa in platelet outside-in signaling using transgenic mice expressing human FcgammaRIIa. PMID- 26809431 TI - Comparative release of growth factors from PRP, PRF, and advanced-PRF. AB - OBJECTIVES: The use of platelet concentrates has gained increasing awareness in recent years for regenerative procedures in modern dentistry. The aim of the present study was to compare growth factor release over time from platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and a modernized protocol for PRF, advanced-PRF (A-PRF). MATERIALS AND METHODS: Eighteen blood samples were collected from six donors (3 samples each for PRP, PRF, and A-PRF). Following preparation, samples were incubated in a plate shaker and assessed for growth factor release at 15 min, 60 min, 8 h, 1 day, 3 days, and 10 days. Thereafter, growth factor release of PDGF-AA, PDGF-AB, PDGF-BB, TGFB1, VEGF, EGF, and IGF was quantified using ELISA. RESULTS: The highest reported growth factor released from platelet concentrates was PDGF-AA followed by PDGF-BB, TGFB1, VEGF, and PDGF-AB. In general, following 15-60 min incubation, PRP released significantly higher growth factors when compared to PRF and A-PRF. At later time points up to 10 days, it was routinely found that A-PRF released the highest total growth factors. Furthermore, A-PRF released significantly higher total protein accumulated over a 10-day period when compared to PRP or PRF. CONCLUSION: The results from the present study indicate that the various platelet concentrates have quite different release kinetics. The advantage of PRP is the release of significantly higher proteins at earlier time points whereas PRF displayed a continual and steady release of growth factors over a 10-day period. Furthermore, in general, it was observed that the new formulation of PRF (A-PRF) released significantly higher total quantities of growth factors when compared to traditional PRF. CLINICAL RELEVANCE: Based on these findings, PRP can be recommended for fast delivery of growth factors whereas A-PRF is better-suited for long-term release. PMID- 26809432 TI - Effect of gamma irradiation on the wear behavior of human tooth dentin. AB - OBJECTIVES: The objective of this study was to evaluate the effect of gamma irradiation on the wear behavior of human tooth dentin in terms of possible alterations in crystallinity, grain size, and composition. MATERIALS AND METHODS: Human premolars (n = 19) were collected to obtain the perpendicular or parallel to the direction of the dentin tubule specimens. Each specimen was subjected to 60 Gy of gamma irradiation, in daily increments of 2 Gy. The nanoscratch tests were conducted. The scratch traces were observed via scanning electron microscope (SEM) and surface profilometer. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) were used to investigate the alteration of crystallography and chemical composition of dentin after irradiation. The change of surface microhardness (SMH) was also evaluated. RESULTS: The nanoscratch results showed that the friction coefficient of dentin after irradiation became higher, and the depths and widths of scratch were greater than that of dentin before irradiation. Additionally, irradiation decreased the crystallinity of dentin and induced the formation of bigger crystals. The carbonate/mineral ratio was increased. Furthermore, a significant reduction in microhardness after irradiation was observed. The main damage mechanisms consisted of the formation of delamination and crack in both the specimens cut perpendicular and parallel to tubule dentin after irradiation. CONCLUSION: Irradiation affected directly the wear behavior of tooth dentin, accompanied by the alterations in crystallography, chemical composition, and surface microhardness of dentin. CLINICAL RELEVANCE: This would help extend understanding the influence of irradiation on dentin and provide suggestions for selecting more suitable materials for irradiated tooth. PMID- 26809434 TI - Erratum to: CMTX1 patients' cells present genomic instability corrected by CamKII inhibitors. PMID- 26809435 TI - What's in a name? PMID- 26809436 TI - Erratum to: Comparative analysis of iterative reconstruction algorithms with resolution recovery and time of flight modeling for 18F-FDG cardiac PET: A multicenter phantom study. PMID- 26809437 TI - Evaluation of general-purpose collimators against high-resolution collimators with resolution recovery with a view to reducing radiation dose in myocardial perfusion SPECT: A preliminary phantom study. AB - BACKGROUND: There is a growing focus on reducing radiation dose to patients undergoing myocardial perfusion imaging. This preliminary phantom study aims to evaluate the use of general-purpose collimators with resolution recovery (RR) to allow a reduction in patient radiation dose. METHODS: Images of a cardiac torso phantom with inferior and anterior wall defects were acquired on a GE Infinia and Siemens Symbia T6 using both high-resolution and general-purpose collimators. Imaging time, a surrogate for administered activity, was reduced between 35% and 40% with general-purpose collimators to match the counts acquired with high resolution collimators. Images were reconstructed with RR with and without attenuation correction. Two pixel sizes were also investigated. Defect contrast was measured. RESULTS: Defect contrast on general-purpose images was superior or comparable to the high-resolution collimators on both systems despite the reduced imaging time. Infinia general-purpose images required a smaller pixel size to be used to maintain defect contrast, while Symbia T6 general-purpose images did not require a change in pixel size to that used for standard myocardial perfusion SPECT. CONCLUSION: This study suggests that general-purpose collimators with RR offer a potential for substantial dose reductions while providing similar or better image quality to images acquired using high-resolution collimators. PMID- 26809438 TI - Diagnosis, therapeutic response assessment, and detection of disease recurrence in cardiac sarcoidosis: Integral role of cardiac PET. PMID- 26809439 TI - The prognostic value of mechanical left ventricular dyssynchrony defined by phase analysis from gated single-photon emission computed tomography myocardial perfusion imaging among patients with coronary heart disease. AB - BACKGROUND: The prognostic value of left ventricular dyssynchrony measured by gated single-photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI) and its relationship to electrical dyssynchrony measured by QRS duration are incompletely understood. The aim of this study was therefore to examine the independent and incremental prognostic value of dyssynchrony in yet the largest group of patients with coronary artery disease (CAD). METHODS AND RESULTS: Patients presenting for GSPECT- MPI between July 1993 and May 1999 in normal sinus rhythm were identified from the Duke Nuclear Cardiology Databank and the Duke Databank for Cardiovascular Disease (N = 1244). After a median of 4.2 years, 336 deaths occurred. At 8 years, the Kaplan-Meier estimates of the probability of death were 34.0% among patients with a phase bandwidth <100 degrees and 56.8% among those with a bandwidth >=100 degrees . After adjustment for standard clinical variables, QRS dyssynchrony was independently associated with death (Hazard Ratio (HR), per 10 degrees : 1.092, 95% Confidence Interval (CI) 1.048,1.139, P < .0001). Phase bandwidth was similarly associated with death after clinical adjustment (HR per 10 degrees : 1.056, 95% CI 1.041,1.072, P < .0001). In clinically adjusted models examining QRS duration in addition to phase bandwidth, phase bandwidth had a stronger association with mortality. After accounting for left ventricular ejection fraction (LVEF), neither QRS duration nor phase bandwidth were statistically significant. Among patients with EF >35%, QRS duration and phase bandwidth together provided value above that provided by LVEF alone (P = 0.0181). When examining cardiovascular death, results were consistent with all-cause death. CONCLUSIONS: Among patients with CAD, mechanical left ventricular dyssynchrony measured by GSPECT MPI has a stronger relationship with outcomes than electrical dyssynchrony measured by QRS duration. After adjustment for baseline characteristics and LVEF, neither mechanical nor electrical dyssynchrony is independently associated with all-cause death or cardiac death. Among patients with EF >35%, mechanical and electrical dyssynchrony together provided prognostic value above that afforded by LVEF. PMID- 26809440 TI - Molecular imaging concepts. PMID- 26809442 TI - Cardiovascular disease guideline adherence and self-reported statin use in longstanding type 1 diabetes: results from the Canadian study of longevity in diabetes cohort. AB - BACKGROUND: Older patients with longstanding type 1 diabetes have high cardiovascular disease (CVD) risk such that statin therapy is recommended independent of prior CVD events. We aimed to determine self-reported CVD prevention guideline adherence in patients with longstanding diabetes. RESEARCH DESIGN AND METHODS: 309 Canadians with over 50 years of type 1 diabetes completed a medical questionnaire for presence of lifestyle and pharmacological interventions, stratified into primary or secondary CVD prevention subgroups based on absence or presence of self-reported CVD events, respectively. Associations with statin use were analyzed using multivariable logistic regression. RESULTS: The 309 participants had mean +/- SD age 65.7 +/- 8.5 years, median diabetes duration 54.0 [IQR 51.0, 59.0] years, and HbA1c of 7.5 +/- 1.1 % (58 mmol/mol). 159 (52.7 %) participants reported diet adherence, 296 (95.8 %) smoking avoidance, 217 (70.5 %) physical activity, 218 (71.5 %) renin-angiotensin system inhibitor use, and 220 (72.1 %) statin use. Physical activity was reported as less common in the secondary prevention subgroup, and current statin use was significantly lower in the primary prevention subgroup (65.5 % vs. 84.8 %, p = 0.0004). In multivariable logistic regression, the odds of statin use was 0.38 [95 % CI 0.15-0.95] in members of the primary compared to the secondary prevention subgroup, adjusting for age, sex, hypertension history, body mass, HbA1c, cholesterol, microvascular complications, acetylsalicylic acid use, and renin-angiotensin system inhibitor use. CONCLUSION: Despite good self-reported adherence to general CVD prevention guidelines, against the principles of these guidelines we found that statin use was substantially lower in those without CVD history. Interventions are needed to improve statin use in older type 1 diabetes patients without a history of CVD. PMID- 26809443 TI - EV71 virus-like particles produced by co-expression of capsid proteins in yeast cells elicit humoral protective response against EV71 lethal challenge. AB - BACKGROUND: Enterovirus 71 (EV71) is the most common causative pathogens of hand, foot and mouth disease (HFMD) associated with severe neurological complications. There is a great need to develop prophylactic vaccine against EV71 infection. RESULTS: EV71 virus-like particle (VLP) was produced in yeast expression system by the co-expression of four EV71 structural proteins VP1-VP4. Immunization with the recombinant VLPs elicited potent anti-EV71 antibody responses in adult mice and anti-VLP sera were able to neutralize EV71 virus in vitro. Neonatal mice model demonstrated VLP immunization conferred protection to suckling mice against the lethal viral challenge. CONCLUSIONS: Co-expression of four EV71 structural proteins VP1-VP4 in yeast expression systems is an effective method to produce EV71 VLPs. VLP-based vaccine shows great potential to prevent EV71 infection. PMID- 26809447 TI - How effective is efinaconazole in the management of onychomycosis? AB - INTRODUCTION: Onychomycosis is a fungal nail infection that is difficult to treat due to poor accessibility of drugs into the nail plate. Although oral antifungals can reach the nail apparatus more readily, these therapies may not be suitable or desirable for some patients (e.g., multiple medications or immunocompromised). Efinaconazole 10% solution is a new topical antifungal recently approved and sold in Canada, the United States and Japan for the treatment of mild-to-moderate toenail onychomycosis. Efinaconazole has broad-spectrum antifungal activity against dermatophytes, nondermatophyte molds and yeasts, and high ungual penetration due to its low keratin binding properties. AREAS COVERED: The objective of this article is to summarize recent data regarding the efficacy, safety and pharmacokinetic properties of efinaconazole in the treatment of onychomycosis. EXPERT OPINION: Efinaconazole is a safe and effective treatment for onychomycosis that can be used in a wide range of patients due to its broad spectrum antifungal activity and low rate of treatment-related adverse events. When incomplete response to oral therapy or devices (e.g. laser therapy) is encountered, efinaconazole could be used in combination to improve success rates. Alternatively, efinaconazole could be used as a 'closer' drug, in an effort to provide cure when the initial oral or device therapy has resulted in an incomplete response. PMID- 26809444 TI - Btn2a2, a T cell immunomodulatory molecule coregulated with MHC class II genes. AB - Evidence has recently emerged that butyrophilins, which are members of the extended B7 family of co-stimulatory molecules, have diverse functions in the immune system. We found that the human and mouse genes encoding butyrophilin-2A2 (BTN2A2) are regulated by the class II trans-activator and regulatory factor X, two transcription factors dedicated to major histocompatibility complex class II expression, suggesting a role in T cell immunity. To address this, we generated Btn2a2-deficient mice. Btn2a2(-/-) mice exhibited enhanced effector CD4(+) and CD8(+) T cell responses, impaired CD4(+) regulatory T cell induction, potentiated antitumor responses, and exacerbated experimental autoimmune encephalomyelitis. Altered immune responses were attributed to Btn2a2 deficiency in antigen presenting cells rather than T cells or nonhematopoietic cells. These results provide the first genetic evidence that BTN2A2 is a co-inhibitory molecule that modulates T cell-mediated immunity. PMID- 26809448 TI - Does provider-initiated HIV testing and counselling lead to higher HIV testing rate and HIV case finding in Rwandan clinics? AB - BACKGROUND: Provider-initiated HIV testing and counselling (PITC) is promoted as a means to increase HIV case finding. We assessed the effectiveness of PITC to increase HIV testing rate and HIV case finding among outpatients in Rwandan health facilities (HF). METHODS: PITC was introduced in six HFs in 2009-2010. HIV testing rate and case finding were compared between phase 1 (pre-PITC) and phase 3 (PITC period) for outpatient-department (OPD) attendees only, and for OPD and voluntary counseling & testing (VCT) departments combined. RESULTS: Out of 26,367 adult OPD attendees in phase 1, 4.7% were tested and out of 29,864 attendees in phase 3, 17.0% were tested (p < 0.001). The proportion of HIV cases diagnosed was 0.25% (67/26,367) in phase 1 and 0.46% (136/29864) in phase 3 (p < 0.001). In multivariable analysis, both testing rate and case finding were significantly higher in phase 3 for OPD attendees. In phase 1 most of the HIV testing was done in VCT departments rather than at the OPD (78.6% vs 21.4% respectively); in phase 3 this was reversed (40.0% vs 60.0%; p < 0.001). In a combined analysis of VCT and OPD attendees, testing rate increased from 18.7% in phase 1 to 25.4% in phase 3, but case finding did not increase. In multivariable analysis, testing rate was significantly higher in phase 3 (OR 1.67; 95% CI 1.60-1.73), but case finding remained stable (OR 1.09; 95% CI 0.93-1.27). CONCLUSION: PITC led to a shift of HIV testing from VCT department to the OPD, a higher testing rate, but no additional HIV case finding. PMID- 26809449 TI - Biopsy-proven pulmonary capillaritis: A retrospective study of aetiologies including an in-depth look at isolated pulmonary capillaritis. AB - BACKGROUND AND OBJECTIVE: Pulmonary capillaritis is generally secondary to a systemic autoimmune process. Little is known regarding other causes of pulmonary capillaritis, particularly isolated pulmonary capillaritis (IPC). IPC is defined as pulmonary capillaritis in the absence of evidence of a systemic disease. We aim to describe the aetiology of biopsy-proven pulmonary capillaritis to add to the existing knowledge on aetiologies of pulmonary capillaritis and provide a more detailed description of IPC cases. METHODS: A retrospective cohort of biopsy proven pulmonary capillaritis was conducted at the Mayo Clinic, Rochester over a 17-year period. Histologic slides were re-reviewed by a lung pathologist. Medical records were reviewed to identify a possible aetiology of the pulmonary capillaritis. A subset analysis of patients identified with IPC was then performed. RESULTS: Thirty-six cases of biopsy-proven pulmonary capillaritis were identified. The majority of cases were secondary to a systemic autoimmune disease, most commonly granulomatosis with polyangiitis. There were four cases of IPC in this cohort. Median follow-up was 116.5 months with no evidence of systemic disease development. No risk factors for IPC were identified. All patients presented sub-acutely with haemoptysis and diffuse alveolar haemorrhage with a delay in diagnosis. After initiation of immunosuppression, most patients obtained remission with a benign clinical course. CONCLUSION: Pulmonary capillaritis is most commonly secondary to systemic autoimmune disorders, predominantly ANCA-associated vasculitis. IPC is a rare form of pulmonary capillaritis with very few cases described in the literature, the availability of effective treatment makes this rare disease important to recognize. PMID- 26809452 TI - Tuning protein mechanics through an ionic cluster graft from an extremophilic protein. AB - Proteins from extremophilic organisms provide excellent model systems to determine the role of non-covalent interactions in defining protein stability and dynamics as well as being attractive targets for the development of robust biomaterials. Hyperthermophilic proteins have a prevalence of salt bridges, relative to their mesophilic homologues, which are thought to be important for enhanced thermal stability. However, the impact of salt bridges on the mechanical properties of proteins is far from understood. Here, a combination of protein engineering, biophysical characterisation, single molecule force spectroscopy (SMFS) and molecular dynamics (MD) simulations directly investigates the role of salt bridges in the mechanical stability of two cold shock proteins; BsCSP from the mesophilic organism Bacillus subtilis and TmCSP from the hyperthermophilic organism Thermotoga maritima. Single molecule force spectroscopy shows that at ambient temperatures TmCSP is mechanically stronger yet, counter-intuitively, its native state can withstand greater deformation before unfolding (i.e. it is mechanically soft) compared with BsCSP. MD simulations were used to identify the location and quantify the population of salt bridges, and reveal that TmCSP contains a larger number of highly occupied salt bridges than BsCSP. To test the hypothesis that salt-bridges endow these mechanical properties on the hyperthermophilic CSP, a charged triple mutant (CTM) variant of BsCSP was generated by grafting an ionic cluster from TmCSP into the BsCSP scaffold. As expected CTM is thermodynamically more stable and mechanically softer than BsCSP. We show that a grafted ionic cluster can increase the mechanical softness of a protein and speculate that it could provide a mechanical recovery mechanism and that it may be a design feature applicable to other proteins. PMID- 26809451 TI - The descriptive epidemiology of total physical activity, muscle-strengthening exercises and sedentary behaviour among Australian adults--results from the National Nutrition and Physical Activity Survey. AB - BACKGROUND: The current Australia's Physical Activity and Sedentary Behaviour Guidelines recommend that adults engage in regular moderate-to-vigorous-intensity physical activity (MVPA) and strength training (ST), and minimise time spent in sedentary behaviours (SB). However, evidence about the specific individual and concurrent distribution of these behaviours in Australia is scarce. Therefore, the aim of this study was to determine the prevalence and sociodemographic correlates of MVPA, ST and SB in a national-representative sample of Australian adults. METHODS: Data were collected using face-to-face interviews, as part of the National Nutrition and Physical Activity Survey 2011-12. The population weighted proportions meeting the MVPA (>= 150 min/week), ST (>= 2 sessions/week) and combined MVPA-ST guidelines, and proportions classified as having 'low levels of SB' (< 480 min/day) were calculated, and their associations with selected sociodemographic and health-related variables were assessed using multiple logistic regression analyses. This was also done for those at potentially 'high risk', defined as insufficient MVPA-ST and 'high-sedentary' behaviour. RESULTS: Out of 9345 participants (response rate = 77.0 %), aged 18-85 years, 52.6 % (95 % CI: 51.2 %-54.0 %), 18.6 % (95 % CI: 17.5 %-19.7 %) and 15.0 % (95 % CI: 13.9 % 16.1 %) met the MVPA, ST and combined MVPA-ST guidelines, respectively. Female gender, older age, low/medium education, poorer self-rated health, being classified as underweight or obese, and being a current smoker were independently associated with lower odds of meeting the MVPA, ST and combined MVPA-ST guidelines. A total of 78.9 % (95 % CI: 77.9 %-80.0 %) were classified as having low levels of SB. Females, older adults and those with lower education were more likely to report lower levels of SB, whilst those with poor self-rated health and obese individuals were less likely to report lower levels of SB (i.e. SB = >= 480 min/day). A total of 8.9 % (95 % CI: 8.1 %-9.6 %) were categorised as individuals at potentially 'high-risk'. Those with poorer self-rated health, obese individuals, those aged 25-44, and current smokers were more likely to be in the 'high risk' group. CONCLUSIONS: The large majority of Australian adults do not meet the full physical activity guidelines and/or report excessive SB. Our results call for public health interventions to reduce physical inactivity and SB in Australia, particularly among the subgroups at the highest risk of these unhealthy behaviours. PMID- 26809453 TI - The MOGE(S) classification : A TNM-like classification for cardiomyopathies. AB - Cardiomyopathy is a disease of the heart muscle resulting from genetic defects, cardiac myocyte injury, or infiltration of the myocardium. Cardiomyopathies are traditionally defined as dilated, restrictive, and hypertrophic cardiomyopathy. Today, the genetic basis of most diseases has been clearly defined and has influenced the approach to familial diseases such as cardiomyopathies. Traditional definitions of cardiomyopathies, such as those by the American Heart Association and the European Society of Cardiology, do not consider the genetic basis of cardiomyopathies. In 2013, the World Heart Federation added the genetic basis of cardiomyopathies and proposed a descriptive genotype-phenotype nosology system termed "MOGE(S)." The MOGE(S) system resembles the TNM classification system for malignancy, and therefore it can be useful for the diagnosis, management, and treatment of cardiomyopathies in a similar manner to cancer management. PMID- 26809454 TI - Renal function after repeat catheter ablation for long-standing persistent atrial fibrillation : Low CHA2DS2-VASc score and sinus rhythm predict improved renal function. AB - BACKGROUND: Renal impairment and atrial fibrillation (AF) often coexist. Catheter ablation is an effective way to reduce the burden of AF and improve symptoms; however, little is known about the relationship between renal function and AF and its role in the progression of AF for patients undergoing repeat catheter ablation. METHODS: In all, 171 patients with long-standing persistent AF ablation were enrolled in the study. The patients were divided into two groups according to their delta estimated glomerular filtration rate (eGFR) values, which was defined as the eGFR before the repeat procedure minus the eGFR before the initial procedure. Patients with decreasing eGFR (delta eGFR < 0) were categorized as group I, while individuals with no change or increasing eGFR (delta eGFR>= 0) were categorized as group II. eGFR was estimated at baseline and at the 12-month and 24-month follow-up visits. RESULTS: After a mean follow-up of 31.4 +/- 13.2 months, group I had a significantly higher arrhythmia recurrence rate than group II (71.2 vs. 49.2 %, p < 0.001). On multivariable analyses, eGFR changes after the repeat procedure were associated with arrhythmia recurrence, hypertrophic cardiomyopathy, and CHA2DS2-VASc score. Patients with arrhythmia recurrence and those with a CHA2DS2-VASc score of >= 3 were more likely to show an eGFR decline at follow-up. CONCLUSION: Patients with long-standing persistent AF, with a failed initial ablation procedure and undergoing a repeat ablation procedure, appear to have a higher risk of arrhythmia recurrence. During the follow-up period, patients without arrhythmia recurrence and those with a CHA2DS2-VASc score of < 3 show improved renal function. PMID- 26809455 TI - [Therapy of mitral regurgitation is set in motion]. PMID- 26809456 TI - Contemporary role of lymph node dissection at the time of radical nephroureterectomy for upper tract urothelial carcinoma. AB - PURPOSE: To review the contemporary data on the role of lymph node dissection (LND) at the time of radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: A computerized bibliographic search using the following protocol ("Nephroureterectomy") AND ("Lymphadenectomy" OR "Lymph node" OR "Lymphatic") was performed in MEDLINE to identify all original and review articles that addressed the role of LND for UTUC. RESULTS: Regional lymph node (LN) boundaries of UTUC have been recently investigated in mapping studies to propose anatomic templates of LND according to the laterality and location of primary tumor. Although these anatomic templates remained poorly described, most reports supported the staging benefit of LND that allowed for risk stratification of patients with (pN+) or without (pN0) LN metastases from those who did not undergo such a procedure (pNx). In addition, the therapeutic benefit of LND at the time of RNU was supported by better oncological outcomes obtained after complete LND when compared to incomplete or no LND, especially in the group of patients with advanced disease. The number of LNs removed was also correlated with both, more accurate staging and greater cancer-specific survival after LND, whose feasibility and safety have been validated in prospective studies. CONCLUSIONS: Despite mostly based on data with level of evidence 3, our comprehensive review of the literature supports the staging and therapeutic benefits of LND at the time of RNU for UTUC, which are particularly significant for patients with muscle-invasive or locally advanced disease. PMID- 26809457 TI - The effects anandamide signaling in the prelimbic cortex and basolateral amygdala on coping with environmental stimuli in rats. AB - RATIONALE: Several lines of recent evidence suggest that endocannabinoids affect behavior by influencing the general patterns of challenge responding. OBJECTIVES: Here, we investigated the brain mechanisms underlying this phenomenon in rats. METHODS: The anandamide hydrolysis inhibitor URB597 was condensed into the tip of stainless steel cannulae, which were chronically implanted slightly above the prelimbic cortex (PRL) or the basolateral amygdala (BLA), two important regions of coping and endocannabinoid action. Thereafter, we investigated behavioral responsiveness to ambient light level in the elevated plus-maze and conditioned fear tests. RESULTS: URB597 concentration was ~30 MUg/mg protein in target areas; local brain anandamide levels increased threefold, without significant changes in 2-arachidonoylglycerol. High levels of illumination halved the time spent by controls in the open arms of the plus-maze. No similar decrease was observed in rats with URB597 implants in the PRL. High light decreased conditioned fear by 30 % in controls, but not in rats with prelimbic URB597 implants. Unresponsiveness to environmental challenges was not attributable to the anxiolytic effects of anandamide enhancement, as implants induced paradoxical anxiogenic-like effects under low light, which could be explained by effects on stimulus responsiveness rather than by effects on anxiety. URB597 implants targeting the BLA did not affect stimulus responsiveness. CONCLUSIONS: Our findings show that elevated prelimbic anandamide signaling leads to less environment-dependent (more autonomous) behavioral responses to challenges, which is an attribute of active coping styles. These findings are discussed in light of two emerging concepts of endocannabinoid roles, particularly "emotional homeostasis" and "active coping." PMID- 26809459 TI - Effect of US Drug Enforcement Administration's Rescheduling of Hydrocodone Combination Analgesic Products on Opioid Analgesic Prescribing. PMID- 26809458 TI - The role of sigma-1 receptor and brain-derived neurotrophic factor in the development of diabetes and comorbid depression in streptozotocin-induced diabetic rats. AB - RATIONALE: Depression is highly prevalent in diabetes (DM). Brain-derived neurotrophic factor (BDNF) which is mainly regulated by the endoplasmic reticulum chaperon sigma-1 receptor (S1R) plays a relevant role in the development of depression. OBJECTIVES: We studied the dose-dependent efficacy of S1R agonist fluvoxamine (FLU) in the prevention of DM-induced depression and investigated the significance of the S1R-BDNF pathway. METHODS: We used streptozotocin to induce DM in adult male rats that were treated for 2 weeks p.o. with either different doses of FLU (2 or 20 mg/bwkg) or FLU + S1R antagonist NE100 (1 mg/bwkg) or vehicle. Healthy controls were also enrolled. Metabolic, behaviour, and neuroendocrine changes were determined, and S1R and BDNF levels were measured in the different brain regions. RESULTS: In DM rats, immobility time was increased, adrenal glands were enlarged, and thymuses were involuted. FLU in 20 mg/bwkg, but not in 2 mg/bwkg dosage, ameliorated depression-like behaviour. S1R and BDNF protein levels were decreased in DM, while FLU induced SIR-BDNF production. NE100 suspended all effects of FLU. CONCLUSIONS: We suggest that disturbed S1R-BDNF signaling in the brain plays a relevant role in DM-induced depression. The activation of this cascade serves as an additional target in the prevention of DM associated depression. PMID- 26809460 TI - Rearrangement of nitrogen metabolism in rice (Oryza sativa L.) under salt stress. AB - Salt stress is an important environmental condition limiting the agricultural production. The reprogram of protein expression is one of the strategies of plants to cope with salt stress. We have previously analyzed the photosynthesis, antioxidant and oxidative phosphorylation involved in the carbon metabolism and the redox metabolism in rice seedlings under salt stress. Here, we focused on the proteins involved in nitrogen metabolic response. As it was reported that the nitrite uptake was enhanced in Arabidopsis PII knock-out mutants, the down regulation of P-II nitrogen sensing protein in rice probably contributes to the accumulation of amino acids under stress. In addition, the protein synthesis is limited by the decrease of related proteins, and more amino acids could be used as the compatible solute. Hence, our study indicates that the rearrangement of nitrogen metabolism under salt stress could accumulate more amino acids as the compatible solute rather than the components of proteins. This study provides information for an improved understanding of nitrogen metabolic response to salt stress in rice. PMID- 26809462 TI - Sleep-disordered Breathing in Cardiac Rehabilitation: Prevalence, Predictors, and Influence on the Six-Minute Walk Test. AB - BACKGROUND: Identification of non-traditional risk factors is an important component of cardiac rehabilitation (CR). However, the prevalence and predictors of sleep-disordered breathing (SDB) and its influence on exercise performance in patients attending CR remain poorly described. METHODS: Patients enrolled in a national CR centre were eligible for a comprehensive SDB screening program. Screening questionnaires for SDB, overnight sleep study, and the 6-minute walk test (6MWT) were conducted. RESULTS: We recruited 332 patients (mean age 62+/-10 years, 62.4% male) attending CR for primary (29.2%) or secondary (70.8%) prevention, of which 209 successfully completed the overnight sleep study. Sleep disordered breathing group patients (n=68, 32.5%) were older and had a higher body mass index (BMI) and neck and waist circumferences than the non-SDB group patients. After adjusting for neck and waist circumference, age (OR=1.06; 95% CI 1.02-1.10; p=0.001) and BMI (OR=1.19; 95% CI 1.10-1.30; p<0.001) remained independent predictors of SDB. A high risk of SDB based on the Berlin Questionnaire (43.4% versus 35.5%, p=0.277) or STOP-BANG questionnaire (63.2% versus 53.2%, p=0.170) and excessive daytime sleepiness (Epworth Sleepiness Scale >10, 23.9% versus 17.7%, p=0.297) were similar between the groups. The 6MWT scores were significantly lower in the SDB than non-SDB group (mean difference 32 m; 95% CI -57-7; p=0.013). The relationship was no longer significant after adjusting for age, sex, and waist circumference. CONCLUSION: Sleep-disordered breathing is prevalent in CR patients and is independently predicted by ageing and obesity. The association between SDB and poorer exercise performance may be explained by age, sex, and waist circumference. PMID- 26809461 TI - Characterization of Gene Expression in the Rat Brainstem After Neonatal Hypoxic Ischemic Injury and Antioxidant Treatment. AB - The perinatal brainstem is known to be very vulnerable to hypoxic-ischemic events which can lead to deafness, swallowing dysfunction, and defective respiratory control. The aim of the present work was to evaluate the potential neuroprotective effects of nicotine, melatonin, resveratrol, and docosahexaenoic acid on the expression of a panel of genes in the brainstem following hypoxic ischemic damage. Quantitative PCR was used to examine gene expression 3 and 12 h after the damage, and immunohistochemistry was employed to evaluate neurons, astrocytes, and synaptic vesicles 24 h post insult. We found that the expression of some immediate-early genes, as well as that of inflammatory genes TNF-alpha, COX2, and caspase 3, was upregulated in response to the insult. Twenty-four hours after the damage, the percentage of NeuN and synaptophysin immunolabeled cells was found to be reduced while GFAP expression was upregulated. No differences were observed in ROS gene expression following treatments. PMID- 26809463 TI - N-terminal Pro-brain Natriuretic Peptide, High-sensitivity Troponin and Pulmonary Artery Clot Score as Predictors of Right Ventricular Dysfunction in Echocardiography. AB - BACKGROUND: We investigated the ability of cardiac biomarkers and total pulmonary artery (PA) clot score to predict right ventricular dysfunction (RVD) on admission and at seven-month follow-up in subjects with acute pulmonary embolism (APE). METHODS: Sixty-three normotensive patients with APE were divided into two groups: patients with (n= 32, age 58+/-19 years) and without (n=31, age 55+/-16 years) echocardiographic RVD. Transthoracic echocardiography (TTE), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT) were assessed upon arrival and repeated at seven months. Total PA clot score was determined on admission. RESULTS: The age- and sex dependent NT-proBNP on admission, on day 5, and at seven months exhibited the best sensitivity (admission 94%, day 5 100%, seven months 100%) and negative predictive value (NPV) (89%, 100%, 100%) for detecting RVD. Six patients (10%) had persistent RVD at seven months. Total PA clot score showed only low to moderate sensitivity (77%) and PPV (7%) for detection of RVD at seven months. CONCLUSIONS: Normal age- and sex dependent NT-proBNP on admission or measured five days later seems to be useful in exclusion of RVD at follow up. Total PA clot score shows only to be of modest benefit for predicting persistent RVD. PMID- 26809464 TI - The Impact of Frailty on Mortality, Length of Stay and Re-hospitalisation in Older Patients with Atrial Fibrillation. AB - BACKGROUND: Frailty has been found to be associated with increased adverse outcomes in older patients, especially in patients with cardiovascular diseases. There has been no study focussing on the prognostic value of frailty amongst older hospitalised patients with atrial fibrillation. This study aims to investigate the impact of frailty on mortality, length of stay and re hospitalisation in older hospitalised patients with atrial fibrillation. METHODS: Prospective observational study in patients aged >=65 years with atrial fibrillation admitted to a teaching hospital in Sydney, Australia. Frailty was assessed using the Reported Edmonton Frail Scale. Participants were followed up for six months for adverse outcomes. RESULTS: We recruited 302 patients (mean age 84.7+/-7.1, 53.3% frail, 50% female). Frailty was associated with prolonged length of stay and increased mortality but not re-admission during six months after discharge. The coexistence of frailty and delirium significantly increased the risk of mortality. CONCLUSIONS: Frailty is a common geriatric syndrome in older inpatients with atrial fibrillation and is associated with poor outcomes. Screening for frailty along with other clinically important factors like delirium should be considered in older patients with atrial fibrillation to optimise individualised treatment plans. PMID- 26809465 TI - Traditional Chinese medicine: potential approaches from modern dynamical complexity theories. AB - Despite the widespread use of traditional Chinese medicine (TCM) in clinical settings, proving its effectiveness via scientific trials is still a challenge. TCM views the human body as a complex dynamical system, and focuses on the balance of the human body, both internally and with its external environment. Such fundamental concepts require investigations using system-level quantification approaches, which are beyond conventional reductionism. Only methods that quantify dynamical complexity can bring new insights into the evaluation of TCM. In a previous article, we briefly introduced the potential value of Multiscale Entropy (MSE) analysis in TCM. This article aims to explain the existing challenges in TCM quantification, to introduce the consistency of dynamical complexity theories and TCM theories, and to inspire future system level research on health and disease. PMID- 26809466 TI - Protein phosphatase magnesium-dependent 1delta is a novel tumor marker and target in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is a lethal liver malignancy worldwide. In this study, we reported that protein phosphatase magnesium-dependent 1delta (PPM1D) was highly expressed in the majority of HCC cases (approximately 59%) and significantly associated with high serum alpha-fetoprotein (AFP) level (P = 0.044). Kaplan- Meier and Cox regression data indicated that PPM1D overexpression was an independent predictor of HCCspecific overall survival (HR, 2.799; 95% CI, 1.346-5.818, P = 0.006). Overexpressing PPM1D promoted cell viability and invasion, whereas RNA interference-mediated knockdown of PPM1D inhibited proliferation, invasion, and migration of cultured HCC cells. In addition, PPM1D suppression by small interfering RNA decreased the tumorigenicity of HCC cells in vivo. Overall, results suggest that PPM1D is a potential prognostic marker and therapeutic target for HCC. PMID- 26809467 TI - Role of intestinal dysfunction in the nutritional compromise seen in human immunodeficiency virus-infected adults in rural India. AB - Human immunodeficiency virus (HIV) disease progression is often marked by significant weight loss with or without chronic diarrhoea. We studied the extent of intestinal dysfunction using a D-xylose absorption test and association with nutritional compromise as measured by body mass index (BMI) and serum antioxidants levels in HIV-infected individuals through a cross-sectional survey of 45 ART naive, HIV-positive and 45, age-socioeconomic status matched negative controls in a rural population in India. More than 40% of HIV-positive and HIV negative participants had intestinal dysfunction (42.2% vs. 44.4%). However an increasing gradient of low D-xylose absorption was noted with decreasing CD4 counts (32%, 50% and 58.3% among those with >350, 200-350 and <200 cells/mm3, respectively). Multivariate analysis revealed a significant association between intestinal dysfunction and low BMI (P = 0.03) independent of HIV infection and calorie intake per day (P = 0.02). Weight loss in HIV-infected individuals should be investigated for intestinal dysfunction especially in low resource settings. PMID- 26809468 TI - Prospective analysis of the quality of Spanish health information web sites after 3 years. AB - OBJECTIVE: Although the Internet has become an essential source of health information, our study conducted 3 years ago provided evidence of the low quality of Spanish health web sites. The objective of the present study was to evaluate the quality of Spanish health information web sites now, and to compare these results with those obtained 3 years ago. METHODS: For the original study, the most visited health information web sites were selected through the PageRank(r) (Google(r)) system. The present study evaluated the quality of the same web sites from February to May 2013, using the method developed by Bermudez-Tamayo et al. and HONCode(r) criteria. RESULTS: The mean quality of the selected web sites was low and has deteriorated since the previous evaluation, especially in regional health services and institutions' web sites. The quality of private web sites remained broadly similar. Compliance with privacy and update criteria also improved in the intervening period. CONCLUSION: The results indicate that, even in the case of health web sites, design or appearance is more relevant to developers than quality of information. It is recommended that responsible institutions should increase their efforts to eliminate low-quality health information that may further contribute to health problems. PMID- 26809470 TI - The effectiveness of psychosocial interventions implemented after the Indian Ocean Tsunami: A systematic review. AB - BACKGROUND: Currently, the number of natural disasters has increased sixfold when compared to the 1960s. The 2004 Indian Ocean Tsunami offered provided an opportunity for scientifically investigating the effectiveness of post-disaster programs across countries with diverse ethnic, religious and cultural backgrounds. AIM: This study aimed to assess the effectiveness of psychological interventions focused on the prevention or reduction in post-traumatic stress disorder (PTSD) symptoms and/or enhancement of psychological well-being implemented after the 2004 Tsunami. METHODS: We systematically searched through MEDLINE, PsycINFO and The Published International Literature on Traumatic Stress (PILOTS) databases using the following keywords: 'tsunami' OR 'Indian Ocean', AND 'intervention'. RESULTS: Our systematic review included 10 studies which adopted 10 different psychological interventions. A total of 8 of the 10 studies reported positive results in reducing PTSD symptoms and most interventions showed high levels of cultural sensitivity. No significant harmful effects of the included interventions were identified although two studies used potentially harmful interventions. CONCLUSION: Evidence-based practice is a process of collaborative decision-making between the affected ones and interventionists. The practitioner assesses not only the availability of the level of evidence of the preferred interventions, but he or she also assesses his or her own expertise, the availability of resources, the surrounding context and the characteristics, values and preferences of relevant stakeholders. PMID- 26809471 TI - Legal regimes surrounding naloxone access: considerations for prescribers. AB - BACKGROUND: Since the late 1980s, opioid-related morbidity and mortality in the United States has dramatically increased. This serious epidemic requires a coordinated medical, public policy, and social response. It is becoming readily apparent that widespread provision of naloxone may help to address this problem. However, because naloxone access laws vary between states, the extent of antidote dissemination may be limited by a given provider's geographic location. OBJECTIVE: This review targets a physician or prescriber audience, in hopes of providing evidence for the safety and utility of naloxone, education on the baseline legal liability of naloxone provision and protections afforded by access laws, and resources for the proposal of statewide legislation to promote antidote distribution. CONCLUSION: Evidence suggests that naloxone administration by laypersons, pursuant to physician prescription or standing order, is safe and effective for reversal of opioid overdose. As of July 2015, 44 states and the District of Columbia have passed naloxone access laws, offering varying degrees of protections for prescribers. Although the likelihood of naloxone-related legal action may parallel that inherent to the usual practice of medicine, providers should be mindful of potential scenarios, exercise methods to mitigate risk, and appreciate the utility of comprehensive naloxone access legislation in orchestrating a coordinated response to the opioid overdose epidemic. PMID- 26809472 TI - Circulating tumor cells in breast cancer. AB - Over the past decade, technically reliable circulating tumor cell (CTC) detection methods allowed the collection of large datasets of CTC counts in cancer patients. These data can be used either as a dynamic prognostic biomarker or as tumor material for "liquid biopsy". Breast cancer appears to be the cancer type in which CTC have been the most extensively studied so far, with level-of evidence-1 studies supporting the clinical validity of CTC count in both early and metastatic stage. This review summarizes and discusses the clinical results obtained in breast cancer patients, the issues faced by the molecular characterization of CTC and the biological findings about cancer biology and metastasis that were obtained from CTC. PMID- 26809473 TI - Population genomics reveals the origin and asexual evolution of human infective trypanosomes. AB - Evolutionary theory predicts that the lack of recombination and chromosomal re assortment in strictly asexual organisms results in homologous chromosomes irreversibly accumulating mutations and thus evolving independently of each other, a phenomenon termed the Meselson effect. We apply a population genomics approach to examine this effect in an important human pathogen, Trypanosoma brucei gambiense. We determine that T.b. gambiense is evolving strictly asexually and is derived from a single progenitor, which emerged within the last 10,000 years. We demonstrate the Meselson effect for the first time at the genome-wide level in any organism and show large regions of loss of heterozygosity, which we hypothesise to be a short-term compensatory mechanism for counteracting deleterious mutations. Our study sheds new light on the genomic and evolutionary consequences of strict asexuality, which this pathogen uses as it exploits a new biological niche, the human population. PMID- 26809474 TI - MHC-compatible bone marrow stromal/stem cells trigger fibrosis by activating host T cells in a scleroderma mouse model. AB - Fibrosis of organs is observed in systemic autoimmune disease. Using a scleroderma mouse, we show that transplantation of MHC compatible, minor antigen mismatched bone marrow stromal/stem cells (BMSCs) play a role in the pathogenesis of fibrosis. Removal of donor BMSCs rescued mice from disease. Freshly isolated PDGFRalpha(+) Sca-1(+) BMSCs expressed MHC class II following transplantation and activated host T cells. A decrease in FOXP3(+) CD25(+) Treg population was observed. T cells proliferated and secreted IL-6 when stimulated with mismatched BMSCs in vitro. Donor T cells were not involved in fibrosis because transplanting T cell-deficient RAG2 knock out mice bone marrow still caused disease. Once initially triggered by mismatched BMSCs, the autoimmune phenotype was not donor BMSC dependent as the phenotype was observed after effector T cells were adoptively transferred into naive syngeneic mice. Our data suggest that minor antigen mismatched BMSCs trigger systemic fibrosis in this autoimmune scleroderma model. PMID- 26809475 TI - Neuronal filopodium formation induced by the membrane glycoprotein M6a (Gpm6a) is facilitated by coronin-1a, Rac1, and p21-activated kinase 1 (Pak1). AB - Stress-responsive neuronal membrane glycoprotein M6a (Gpm6a) functions in neurite extension, filopodium and spine formation and synaptogenesis. The mechanisms of Gpm6a action in these processes are incompletely understood. Previously, we identified the actin regulator coronin-1a (Coro1a) as a putative Gpm6a interacting partner. Here, we used co-immunoprecipitation assays with the anti Coro1a antibody to show that Coro1a associates with Gpm6a in rat hippocampal neurons. By immunofluorescence microscopy, we demonstrated that in hippocampal neurons Coro1a localizes in F-actin-enriched regions and some of Coro1a spots co localize with Gpm6a labeling. Notably, the over-expression of a dominant-negative form of Coro1a as well as its down-regulation by siRNA interfered with Gpm6a induced filopodium formation. Coro1a is known to regulate the plasma membrane translocation and activation of small GTPase Rac1. We show that Coro1a co immunoprecipitates with Rac1 together with Gpm6a. Pharmacological inhibition of Rac1 resulted in a significant decrease in filopodium formation by Gpm6a. The same was observed upon the co-expression of Gpm6a with the inactive GDP-bound form of Rac1. In this case, the elevated membrane recruitment of GDP-bound Rac1 was detected as well. Moreover, the kinase activity of the p21-activated kinase 1 (Pak1), a main downstream effector of Rac1 that acts downstream of Coro1a, was required for Gpm6a-induced filopodium formation. Taken together, our results provide evidence that a signaling pathway including Coro1a, Rac1, and Pak1 facilitates Gpm6a-induced filopodium formation. Formation of filopodia by membrane glycoprotein M6a (Gpm6a) requires actin regulator coronin-1a (Coro1a), known to regulate plasma membrane localization and activation of Rac1 and its downstream effector Pak1. Coro1a associates with Gpm6a. Blockage of Coro1a, Rac1, or Pak1 interferes with Gpm6a-induced filopodium formation. Moreover, Gpm6a facilitates Rac1 membrane recruitment. Altogether, a mechanistic insight into the process of Gpm6a-induced neuronal filopodium formation is provided. PMID- 26809477 TI - Use of the Health Belief Model to Study Patient Perceptions of Antimicrobial Stewardship in the Acute Care Setting. AB - OBJECTIVE: To identify themes associated with patient perceptions of antibiotic use and the role of patients in inpatient antimicrobial stewardship. DESIGN: We conducted semi-structured interviews with 30 hospitalized patients using the Health Belief Model as the framework for questions and analysis. SETTING: An academic tertiary care hospital in Madison, Wisconsin. PARTICIPANTS: A total of 30 general medicine inpatients receiving at least 1 anti-infective medication were interviewed. RESULTS: Participants recognized antibiotic resistance as a serious public health threat but expressed low perceived susceptibility to being personally affected by antibiotic resistance. Views of susceptibility were influenced by a high degree of trust in physicians and misperceptions regarding the mechanisms underlying resistance. Participants expressed high self-efficacy and a desire to be involved in their health care. Perceived roles for patients in preventing the inappropriate use of antibiotics ranged from asking questions and speaking up about concerns to active involvement in decision making regarding antibiotic treatments. Few participants reported being offered the opportunity to engage in such shared decision making while hospitalized. CONCLUSIONS: Our findings suggest an important role for patients in improving antibiotic use in hospitals. However, patient engagement has not been recognized as a critical component of antimicrobial stewardship programs. Our study suggests that the likelihood of patient engagement in stewardship practices is currently limited by low perceived susceptibility and lack of cues to act. Further investigation into how patients may be engaged as good stewards of antibiotics may reveal new ways to improve antibiotic prescribing practices in the inpatient setting. PMID- 26809479 TI - Concentrations of organochlorine pesticides, polybrominated diphenyl ethers and perfluorinated compounds in the atmosphere of North Greenland. AB - Atmospheric concentrations of organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs) and neutral per- and polyfluoroalkyl substances (PFAS) have been measured at Villum Research Station, Station Nord (North Greenland) in the period 2008-2013. Atmospheric concentrations of OCPs at the same site have been previously reported for the years 2008-2010. The detection frequency and the average concentrations of OCPs have not significantly changed since the previous study. PBDE congeners (?13PBDEs) were measured for the first time in North Greenland at concentrations similar to those observed for other remote sites, confirming that these compounds are ubiquitous in the Northern Hemisphere. The ?13PBDEs concentration ranged from not detected (n.d.) to 6.26 pg m(-3). The BDE congeners found in more than 30% of the samples were BDE-17, BDE-28, BDE-47, BDE 71, BDE-99 and BDE-100. Also for neutral PFAS we present for the first time a multiyear series of measurements for North Greenland. The average sum of the seven measured neutral PFAS (?7PFAS) ranged from 1.82 to 32.1 pg m(-3). The most abundant compound was 8:2 FTOH (44% of ?7PFAS), followed by 6:2 FTOH and 10:2 FTOH. Perfluoroalkyl sulfonamides (FOSA) and perfluoroalkyl sulfonamidoethanols (FOSE) were also detected but at much lower concentrations than FTOHs. Temporal trends were investigated for all measured compounds but no significant trend in concentration was observed. Monthly average concentrations for the six years were calculated for each compound and the seasonal variation was investigated. Some OCPs and FTOHs showed seasonal variations, and in most cases a maximum was found during summer. PMID- 26809480 TI - The first toxicological study of the antiozonant and research tool ethylene diurea (EDU) using a Lemna minor L. bioassay: Hints to its mode of action. AB - The antiozonant and research tool ethylene diurea (EDU) is widely studied as a phytoprotectant against the widespread pollutant ground-surface ozone. Although it has been extensively used, its potential toxicity in the absence of ozone is unknown and its mode of action is unclear. The purpose of this research was to toxicologically assess EDU and to further investigate its mode of action using Lemna minor L. as a model organism. Application of EDU concentrations greater than 593 mg L(-1) (practically 600 mg L(-1)) resulted in adverse inhibition of colony growth. As no-observed-toxic-effects concentration (NOEL) we recommend a concentration of 296 mg L(-1) (practically 300 mg L(-1)). A hormetic response was detected, i.e. stimulatory effects of low EDU concentrations, which may indicate overcompensation in response to disruption in homeostasis. Growth inhibition and suppressed biomass were associated with impacted chlorophyll a fluorescence (PhiPSII, qP and ETR). Furthermore, EDU increased mesophyll thickness, as indicated by frond succulence index. Applications of concentrations >=593 mg L( 1) to uncontrolled environments should be avoided due to potential toxicity to sensitive organisms and the environment. PMID- 26809482 TI - Familial autoimmunity and polyautoimmunity in 60 Brazilian Midwest patients with systemic sclerosis. AB - INTRODUCTION: Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology, characterized by a triad of vascular injury, autoimmunity and tissue fibrosis. It is known that a positive family history is the greatest risk factor already identified for the development of SSc in a given individual. Preliminary observation of a high prevalence of poliautoimmunity and of familial autoimmunity in SSc patients support the idea that different autoimmune phenotypes may share common susceptibility variants. OBJECTIVES: To describe the frequency of familial autoimmunity and poliautoimmunity in 60 SSc patients in the Midwest region of Brazil, as well as to report the main autoimmune diseases observed in this association of comorbidities. METHODS: A cross-sectional study with recruitment of 60 consecutive patients selected at the Rheumatology Department, University Hospital, Medicine School, Federal University of Mato Grosso do Sul (FMUFMS), as well as interviews of their relatives during the period from February 2013 to March 2014. RESULTS: A frequency of 43.3% of poliautoimmunity and of 51.7% of familial autoimmunity in SSc patients was found. Patients with presence of poliautoimmunity and familial autoimmunity presented primarily the diffuse form of SSc, but this indicator did not reach statistical significance. The autoimmune diseases most frequently observed in poliautoimmunity patients were: Hashimoto's thyroiditis (53.8%), Sjogren's syndrome (38.5%), and inflammatory myopathy (11.5%). The main autoimmune diseases observed in SSc patients' relatives were: Hashimoto's thyroiditis (32.3%), rheumatoid arthritis (22.6%), and SLE (22.6%). The presence of more than one autoimmune disease in SSc patients did not correlate with disease severity or activity. CONCLUSIONS: From the high prevalence of coexisting autoimmune diseases found in SSc patients, we stress the importance of the concept of shared autoimmunity, in order to promote a continued vigilance and promptly diagnose other possible autoimmune disease in patients, or in their kin. PMID- 26809483 TI - SmartFABER: Recognizing fine-grained abnormal behaviors for early detection of mild cognitive impairment. AB - OBJECTIVE: In an ageing world population more citizens are at risk of cognitive impairment, with negative consequences on their ability of independent living, quality of life and sustainability of healthcare systems. Cognitive neuroscience researchers have identified behavioral anomalies that are significant indicators of cognitive decline. A general goal is the design of innovative methods and tools for continuously monitoring the functional abilities of the seniors at risk and reporting the behavioral anomalies to the clinicians. SmartFABER is a pervasive system targeting this objective. METHODS: A non-intrusive sensor network continuously acquires data about the interaction of the senior with the home environment during daily activities. A novel hybrid statistical and knowledge-based technique is used to analyses this data and detect the behavioral anomalies, whose history is presented through a dashboard to the clinicians. Differently from related works, SmartFABER can detect abnormal behaviors at a fine-grained level. RESULTS: We have fully implemented the system and evaluated it using real datasets, partly generated by performing activities in a smart home laboratory, and partly acquired during several months of monitoring of the instrumented home of a senior diagnosed with MCI. Experimental results, including comparisons with other activity recognition techniques, show the effectiveness of SmartFABER in terms of recognition rates. PMID- 26809486 TI - Trimethylamine-The Extracorporeal Envoy. AB - One of the most widespread and efficient mechanisms that has evolved to enable communication between discrete and spatially separate living organisms is the use of specific chemical messengers. The organoleptic properties of certain molecules, even at concentrations that do not necessarily evoke a conscious response, have been exploited to transmit information across relatively large distances. The trimethylated derivative of ammonia is one such molecule that is ideally suited to this function and several species are known to respond to its presence. This review uniquely collects together and integrates widely dispersed data to show that trimethylamine also may serve a communicatory role in man, with its influence extending outside of the body. PMID- 26809485 TI - Olfactory Dysfunction in Older Adults is Associated with Feelings of Depression and Loneliness. AB - Olfactory dysfunction is a common complaint among physician visits. Olfactory loss affects quality of life and impairs function and activities of daily living. The purpose of our study was to assess the degree of odor identification associated with mental health. Olfactory function was measured using the brief smell identification test. Depressive symptoms were measured by the Center for Epidemiologic Studies Depression scale. Loneliness was assessed by the de Jong Gierveld Loneliness Scale. Cognition was measured by a battery of 19 cognitive tests. The frequency of olfactory dysfunction in our study was ~40%. Older subjects had worse olfactory performance, as previously found. More loneliness was associated with worse odor identification. Similarly, symptoms of depression were associated with worse olfaction (among men). Although better global cognitive function was strongly associated with better odor identification, after controlling for multiple factors, the associations with depression and loneliness were unchanged. Clinicians should assess these mental health conditions when treating older patients who present with olfactory deficits. PMID- 26809484 TI - Comparison of probiotic lactobacilli and bifidobacteria effects, immune responses and rotavirus vaccines and infection in different host species. AB - Different probiotic strains of Lactobacillus and Bifidobacterium genera possess significant and widely acknowledged health-promoting and immunomodulatory properties. They also provide an affordable means for prevention and treatment of various infectious, allergic and inflammatory conditions as demonstrated in numerous human and animal studies. Despite the ample evidence of protective effects of these probiotics against rotavirus (RV) infection and disease, the precise immune mechanisms of this protection remain largely undefined, because of limited mechanistic research possible in humans and investigated in the majority of animal models. Additionally, while most human clinical probiotic trials are well-standardized using the same strains, uniform dosages, regimens of the probiotic treatments and similar host age, animal studies often lack standardization, have variable experimental designs, and non-uniform and sometime limited selection of experimental variables or observational parameters. This review presents selected data on different probiotic strains of lactobacilli and bifidobacteria and summarizes the knowledge of their immunomodulatory properties and the associated protection against RV disease in diverse host species including neonates. PMID- 26809487 TI - Area-level Socioeconomic Inequalities in the Use of Mammography Screening: A Multilevel Analysis of the Health of Houston Survey. AB - BACKGROUND: An emerging literature reports that women who reside in socioeconomically deprived communities are less likely to adhere to mammography screening. This study explored associations between area-level socioeconomic measures and mammography screening among a racially and ethnically diverse sample of women in Texas. METHODS: We conducted a cross-sectional, multilevel study linking individual-level data from the 2010 Health of Houston Survey and contextual data from the U.S. Census. Women ages 40 to 74 years (n = 1,541) were included in the analyses. We examined tract-level poverty, unemployment, education, Hispanic and Black composition, female-headed householder families, and crowding as contextual measures. Using multilevel logistic regression modeling, we compared most disadvantaged tracts (quartiles 2-4) to the most advantaged tract (quartile 1). RESULTS: Overall, 64% of the sample was adherent to mammography screening. Screening rates were lower (p < .05) among Hispanics, those foreign born, women aged 40 to 49 years, and those with low educational attainment, unemployed, and without health insurance coverage. Women living in areas with high levels of poverty (quartile 2 vs. 1: odds ratio [OR], 0.50; 95% CI, 0.30-0.85), Hispanic composition (quartile 3 vs. 1: OR, 0.54; 95% CI, 0.32 0.90), and crowding (quartile 4 vs. 1: OR, 0.53; 95% CI, 0.29-0.96) were less likely to have up-to-date mammography screening, net of individual-level factors. CONCLUSION: Our findings highlight the importance of examining area-level socioeconomic inequalities in mammography screening. The study represents an advance on previous research because we examined multiple area measures, controlled for key individual-level covariates, used data aggregated at the tract level, and accounted for the nested structure of the data. PMID- 26809489 TI - A versatile sonication-assisted deposition-reduction method for preparing supported metal catalysts for catalytic applications. AB - This work aims to develop a rapid and efficient strategy for preparing supported metal catalysts for catalytic applications. The sonication-assisted reduction precipitation method was employed to prepare the heterogeneous mono- and bi metallic catalysts for photocatalytic degradation of methyl orange (MO) and preferential oxidation (PROX) of CO in H2-rich gas. In general, there are three advantages for the sonication-assisted method as compared with the conventional methods, including high dispersion of metal nanoparticles on the catalyst support, the much higher deposition efficiency (DE) than those of the deposition precipitation (DP) and co-precipitation (CP) methods, and the very fast preparation, which only lasts 10-20s for the deposition. In the AuPd/TiO2 catalysts series, the AuPd(3:1)/TiO2 catalyst is the most active for MO photocatalytic degradation; while for PROX reaction, Ru/TiO2, Au-Cu/SBA-15 and Pt/gamma-Al2O3 catalysts are very active, and the last one showed high stability in the lifetime test. The structural characterization revealed that in the AuPd(3:1)/TiO2 catalyst, Au-Pd alloy particles were formed and a high percentage of Au atoms was located at the surface. Therefore, this sonication-assisted method is efficient and rapid in the preparation of supported metal catalysts with obvious structural characteristics for various catalytic applications. PMID- 26809490 TI - Histone Deacetylase Inhibitors Enhance the Therapeutic Potential of Reovirus in Multiple Myeloma. AB - Multiple myeloma remains incurable and the majority of patients die within 5 years of diagnosis. Reolysin, the infusible form of human reovirus (RV), is a novel viral oncolytic therapy associated with antitumor activity likely resulting from direct oncolysis and a virus-mediated antitumor immune response. Results from our phase I clinical trial investigating single agent Reolysin in patients with relapsed multiple myeloma confirmed tolerability, but no objective responses were evident, likely because the virus selectively entered the multiple myeloma cells but did not actively replicate. To date, the precise mechanisms underlying the RV infectious life cycle and its ability to induce oncolysis in patients with multiple myeloma remain unknown. Here, we report that junctional adhesion molecule 1 (JAM-1), the cellular receptor for RV, is epigenetically regulated in multiple myeloma cells. Treatment of multiple myeloma cells with clinically relevant histone deacetylase inhibitors (HDACi) results in increased JAM-1 expression as well as increased histone acetylation and RNA polymerase II recruitment to its promoter. Furthermore, our data indicate that the combination of Reolysin with HDACi, potentiates RV killing activity of multiple myeloma cells in vitro and in vivo This study provides the molecular basis to use these agents as therapeutic tools to increase the efficacy of RV therapy in multiple myeloma. Mol Cancer Ther; 15(5); 830-41. (c)2016 AACR. PMID- 26809491 TI - Bevacizumab Prevents Brain Metastases Formation in Lung Adenocarcinoma. AB - Patients with nonsquamous non-small cell lung cancer (nsNSCLC; largely lung adenocarcinoma) are at high risk of developing brain metastases. Preclinical data suggested that anti-VEGF-A therapy may prevent the formation of nsNSCLC brain metastases. Whether non-brain metastases are also prevented, and whether bevacizumab shows a brain metastases-preventive activity in cancer patients is unknown. Data of one nsNSCLC (stage IIIB/IV, AVAiL) and two breast cancer bevacizumab trials (HER2 negative, AVADO; HER2 positive, AVEREL) were retrospectively analyzed regarding the frequency of the brain versus other organs being the site of first relapse. For animal studies, the outgrowth of PC14-PE6 lung adenocarcinoma cells to brain macrometastases in mice was measured by intravital imaging: under control IgG (25 mg/kg) treatment, or varying doses of bevacizumab (25 mg/kg, 2.5 mg/kg, 0.25 mg/kg). Brain metastases as site of first relapse were significantly less frequent in the bevacizumab arm of the AVAiL trial (HR = 0.36, P < 0.001). In AVADO and AVEREL, no significant difference was seen. In mice, bevacizumab treatment led to secondary regressions of non-brain macrometastases, but did not reduce their total incidence, and did not improve survival. In a brain-seeking nsNSCLC metastasis model, treatment with bevacizumab inhibited brain metastases formation, which resulted in improved overall survival. In summary, bevacizumab has the potential to prevent brain metastases in nsNSCLC, but no preventive activity could be detected outside the brain. These data indicate that anti-VEGF-A agents might be particularly relevant for those stage III nsNSCLC patients who are at high risk to develop future brain metastases. Mol Cancer Ther; 15(4); 702-10. (c)2016 AACR. PMID- 26809492 TI - Patterns of outpatient care utilization by seniors under the National Health Insurance in Taiwan. AB - BACKGROUND/PURPOSE: Taiwan has one of the fastest growing aging populations in the world, which makes the effective allocation of scarce medical resources a key issue. This paper investigates patterns in the use of outpatient services by elderly individuals in Taiwan under the National Health Insurance (NHI) program. METHODS: We assembled a random sample from the NHI Research Database in Taiwan, comprising 50% of all claims made for elderly people (65 years old) in 2010 (n 1,239,836 beneficiaries) including 14 variables. RESULTS: In 2010, individuals aged 65 years or older comprised 10.74% of the population of Taiwan, and accounted for 11.39% of all physician and outpatient visits. The rate of medical care visits was 28.54 +/- 21.23 (Standard deviation) times per person per annum, with a higher rate for women, those in the 80-84 age group, low-income beneficiaries, and the inhabitants of offshore islands. The three most frequent diagnoses for elderly patients were hypertension, diabetes, and acute upper respiratory infections. The mean insured medical costs per person per annum were US Dollars 1,132, with higher expenses for men, those in the 80-84 age group, and those inhabiting urban areas. CONCLUSION: This study employed nationally representative data in the detection of patterns in outpatient care utilization by elderly individuals in Taiwan. Medical care providers and policymakers should be fully aware of the complex patterns unique to older patients. The results of this study could be used as a benchmark with which to assess the impact of future medical care policy on elderly people. PMID- 26809494 TI - Determination of some psychotropic drugs in serum and saliva samples by HPLC-DAD and HPLC MS. AB - A simple, rapid and sensitive HPLC-DAD method has been developed and validated for the simultaneous determination of seven psychotropic drugs (risperidone, citalopram, clozapine,quetiapine, levomepromazine, perazine and aripiprazole) in human serum or saliva samples. The chromatographic analyses were performed on a XSELECT CSH Phenyl-Hexyl column with a mobile phase containing methanol, acetate buffer at pH 3.5 and 0.025mL(-1) diethylamine. The influence of concentration of methanol in injection samples and injection volume on peak symmetry and system efficiency was examined.The full separation of all investigated drugs, good peaks' symmetry and simultaneously high systems efficiency were obtained in applied chromatographic system. The method is suitable for the analysis of investigated drugs in human plasma or saliva for psychiatric patients for control of pharmacotherapy, particularly in combination therapy. HPLC-MS was applied for verification of the presence of drugs and their metabolites in serum and saliva samples from patients. PMID- 26809495 TI - Older Is Not Wiser, Immunologically Speaking: Effect of Aging on Host Response to Clostridium difficile Infections. AB - Clostridium difficile infection (CDI) is the most common cause of antibiotic associated diarrhea and a significant burden on the health care system. Aging has been identified in the literature as a risk factor for CDI as well as adverse outcome from CDI. Although this effect of advanced age on CDI could be partially explained by clinical factors associated with aging, biologic factors are important. Innate immune system, responsible for immediate response to acute infections, plays a major role in CDI pathogenesis. Impairment in function of innate immunity with aging, demonstrated in other infection models, may lead to worse outcome with CDI. C. difficile toxin-specific antibody response protects the host against initial and recurrent infections as shown in observational studies and clinical trial. Effect of aging on antibody response to CDI has not been demonstrated, but the results from vaccine studies in other infections suggest a negative effect on humoral immunity from aging. Although intestinal microbiota from healthy people confers resistance to CDI by preventing C. difficile colonization, changes in composition of microbiota with aging may affect that resistance and increase risk for CDI. There are also age-associated changes in physiology, especially of the gastrointestinal tract, that may play a role in CDI risk and outcomes. In this review, we will first discuss the epidemiology of CDI in the elderly people, then the alteration in innate immunity, humoral response, and microbiota that increases susceptibility to CDI and severe disease and lastly, the physiological and functional changes that may modify outcomes of infection. PMID- 26809496 TI - Rapamycin Attenuates Age-associated Changes in Tibialis Anterior Tendon Viscoelastic Properties. AB - Rapamycin extends mouse life span, but the extent to which rapamycin prevents aging-associated changes in specific tissues remains unclear. Stiffness increases and collagen turnover decreases in mouse tendon with aging; thus, our aim was to determine the effect of long-term rapamycin treatment on the mechanical and structural properties of tendons from old mice. Tendons were harvested from female UM-HET3 mice maintained on a standard chow diet for 4 (adult) or 22 (old) months or fed chow containing polymer-encapsulated rapamycin (eRAPA) from 9 to 22 months of age (old RAPA). Stiffness was twofold higher for tendons of old compared with adult mice, but in old RAPA mice, tendon stiffness was maintained at a value not different from that of adults. Additionally, expression of collagen decreased, expression of matrix metalloproteinase-8 increased, and total hydroxyproline content trended toward decreased levels in tendons of old eRAPA fed mice compared with controls. Finally, age-associated calcification of Achilles tendons and accompanying elevations in expression of chondrocyte and osteoblast markers were all lower in old eRAPA-fed mice. These results suggest that long-term administration of rapamycin alters the molecular pathways responsible for aging of tendon extracellular matrix, resulting in tissue that is structurally and mechanically similar to tendons in adult mice. PMID- 26809498 TI - Recalcitrant molluscum contagiosum successfully treated with sinecatechins. PMID- 26809497 TI - 17alpha-Estradiol Alleviates Age-related Metabolic and Inflammatory Dysfunction in Male Mice Without Inducing Feminization. AB - Aging is associated with visceral adiposity, metabolic disorders, and chronic low grade inflammation. 17alpha-estradiol (17alpha-E2), a naturally occurring enantiomer of 17beta-estradiol (17beta-E2), extends life span in male mice through unresolved mechanisms. We tested whether 17alpha-E2 could alleviate age related metabolic dysfunction and inflammation. 17alpha-E2 reduced body mass, visceral adiposity, and ectopic lipid deposition without decreasing lean mass. These declines were associated with reductions in energy intake due to the activation of hypothalamic anorexigenic pathways and direct effects of 17alpha-E2 on nutrient-sensing pathways in visceral adipose tissue. 17alpha-E2 did not alter energy expenditure or excretion. Fasting glucose, insulin, and glycosylated hemoglobin were also reduced by 17alpha-E2, and hyperinsulinemic-euglycemic clamps revealed improvements in peripheral glucose disposal and hepatic glucose production. Inflammatory mediators in visceral adipose tissue and the circulation were reduced by 17alpha-E2. 17alpha-E2 increased AMPKalpha and reduced mTOR complex 1 activity in visceral adipose tissue but not in liver or quadriceps muscle, which is in contrast to the generalized systemic effects of caloric restriction. These beneficial phenotypic changes occurred in the absence of feminization or cardiac dysfunction, two commonly observed deleterious effects of exogenous estrogen administration. Thus, 17alpha-E2 holds potential as a novel therapeutic for alleviating age-related metabolic dysfunction through tissue specific effects. PMID- 26809499 TI - Comprehensive profiling reveals mechanisms of SOX2-mediated cell fate specification in human ESCs and NPCs. AB - SOX2 is a key regulator of multiple types of stem cells, especially embryonic stem cells (ESCs) and neural progenitor cells (NPCs). Understanding the mechanism underlying the function of SOX2 is of great importance for realizing the full potential of ESCs and NPCs. Here, through genome-wide comparative studies, we show that SOX2 executes its distinct functions in human ESCs (hESCs) and hESC derived NPCs (hNPCs) through cell type- and stage-dependent transcription programs. Importantly, SOX2 suppresses non-neural lineages in hESCs and regulates neurogenesis from hNPCs by inhibiting canonical Wnt signaling. In hESCs, SOX2 achieves such inhibition by direct transcriptional regulation of important Wnt signaling modulators, WLS and SFRP2. Moreover, SOX2 ensures pluripotent epigenetic landscapes via interacting with histone variant H2A.Z and recruiting polycomb repressor complex 2 to poise developmental genes in hESCs. Together, our results advance our understanding of the mechanism by which cell type-specific transcription factors control lineage-specific gene expression programs and specify cell fate. PMID- 26809502 TI - Modelling the impact of climate change and atmospheric N deposition on French forests biodiversity. AB - A dynamic coupled biogeochemical-ecological model was used to simulate the effects of nitrogen deposition and climate change on plant communities at three forest sites in France. The three sites had different forest covers (sessile oak, Norway spruce and silver fir), three nitrogen loads ranging from relatively low to high, different climatic regions and different soil types. Both the availability of vegetation time series and the environmental niches of the understory species allowed to evaluate the model for predicting the composition of the three plant communities. The calibration of the environmental niches was successful, with a model performance consistently reasonably high throughout the three sites. The model simulations of two climatic and two deposition scenarios showed that climate change may entirely compromise the eventual recovery from eutrophication of the simulated plant communities in response to the reductions in nitrogen deposition. The interplay between climate and deposition was strongly governed by site characteristics and histories in the long term, while forest management remained the main driver of change in the short term. PMID- 26809501 TI - Integrated analysis of the prostate cancer small-nucleolar transcriptome reveals SNORA55 as a driver of prostate cancer progression. AB - Metastasis is the primary cause of death in prostate cancer (PCa) patients. Small nucleolar RNAs (snoRNAs) have long been considered "housekeeping" genes with no relevance for cancer biology. Emerging evidence has challenged this assumption, suggesting that snoRNA expression is frequently modulated during cancer progression. Despite this, no study has systematically addressed the prognostic and functional significance of snoRNAs in PCa. We performed RNA Sequencing on paired metastatic/non-metastatic PCa xenografts derived from clinical specimens. The clinical significance of differentially expressed snoRNAs was further investigated in two independent primary PCa cohorts (131 and 43 patients, respectively). The snoRNA demonstrating the strongest association with clinical outcome was quantified in PCa patient-derived serum samples and its functional relevance was investigated in PCa cells via gene expression profiling, pathway analysis and gene silencing. Our comparison revealed 21 differentially expressed snoRNAs in the metastatic vs. non-metastatic xenografts. Of those, 12 were represented in clinical databases and were further analyzed. SNORA55 emerged as a predictor of shorter relapse-free survival (results confirmed in two independent databases). SNORA55 was reproducibly detectable in serum samples from PCa patients. SNORA55 silencing in PCa cell lines significantly inhibited cell proliferation and migration. Pathway analysis revealed that SNORA55 expression is significantly associated with growth factor signaling and pro-inflammatory cytokine expression in PCa. Our results demonstrate that SNORA55 up-regulation predicts PCa progression and that silencing this non-coding gene affects PCa cell proliferation and metastatic potential, thus positioning it as both a novel biomarker and therapeutic target. PMID- 26809503 TI - BVOC responses to realistic nitrogen fertilization and ozone exposure in silver birch. AB - Emission of BVOC (Biogenic Volatile Organic Compounds) from plant leaves in response to ozone exposure (O3) and nitrogen (N) fertilization is poorly understood. For the first time, BVOC emissions were explored in a forest tree species (silver birch, Betula pendula) exposed for two years to realistic levels of O3 (35, 48 and 69 ppb as daylight average) and N (10, 30 and 70 kg ha(-1) yr( 1), applied weekly to the soil as ammonium nitrate). The main BVOCs emitted were: alpha-pinene, beta-pinene, limonene, ocimene, (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT) and hexanal. Ozone exposure increased BVOC emission and reduced total leaf area. The effect on emission was stronger when a short-term O3 metric (concentrations at the time of sampling) rather than a long-term one (AOT40) was used. The effect of O3 on total leaf area was not able to compensate for the stimulation of emission, so that responses to O3 at leaf and whole-plant level were similar. Nitrogen fertilization increased total leaf area, decreased alpha pinene and beta-pinene emission, and increased ocimene, hexanal and DMNT emission. The increase of leaf area changed the significance of the emission response to N fertilization for most compounds. Nitrogen fertilization mitigated the effects of O3 exposure on total leaf area, while the combined effects of O3 exposure and N fertilization on BVOC emission were additive and not synergistic. In conclusion, O3 exposure and N fertilization have the potential to affect global BVOC via direct effects on plant emission rates and changes in leaf area. PMID- 26809504 TI - The European Narcolepsy Network (EU-NN) database. AB - Narcolepsy with cataplexy is a rare disease with an estimated prevalence of 0.02% in European populations. Narcolepsy shares many features of rare disorders, in particular the lack of awareness of the disease with serious consequences for healthcare supply. Similar to other rare diseases, only a few European countries have registered narcolepsy cases in databases of the International Classification of Diseases or in registries of the European health authorities. A promising approach to identify disease-specific adverse health effects and needs in healthcare delivery in the field of rare diseases is to establish a distributed expert network. A first and important step is to create a database that allows collection, storage and dissemination of data on narcolepsy in a comprehensive and systematic way. Here, the first prospective web-based European narcolepsy database hosted by the European Narcolepsy Network is introduced. The database structure, standardization of data acquisition and quality control procedures are described, and an overview provided of the first 1079 patients from 18 European specialized centres. Due to its standardization this continuously increasing data pool is most promising to provide a better insight into many unsolved aspects of narcolepsy and related disorders, including clear phenotype characterization of subtypes of narcolepsy, more precise epidemiological data and knowledge on the natural history of narcolepsy, expectations about treatment effects, identification of post-marketing medication side-effects, and will contribute to improve clinical trial designs and provide facilities to further develop phase III trials. PMID- 26809505 TI - Pleurotus eryngii Polysaccharide Promotes Pluripotent Reprogramming via Facilitating Epigenetic Modification. AB - Pleurotus eryngii is a medicinal/edible mushroom with great nutritional value and bioactivity. Its polysaccharide has recently been developed into an effective gene vector via cationic modification. In the present study, cationized P. eryngii polysaccharide (CPS), hybridized with calcium phosphate (CP), was used to codeliver plasmids (Oct4, Sox2, Klf4, c-Myc) for generating induced pluripotent stem cells (iPSCs). The results revealed that the hybrid nanoparticles could significantly enhance the process and efficiency of reprogramming (1.6-fold increase) compared with the CP nanoparticles. The hybrid CPS also facilitated epigenetic modification during the reprogramming. Moreover, these hybrid nanoparticles exhibited multiple pathways (both caveolae- and clathrin-mediated endocytosis) in their cellular internalization, which accounted for the improved iPSCs generation. These findings therefore present a novel application of P. eryngii polysaccharide in pluripotent reprogramming via active epigenetic modification. PMID- 26809506 TI - The implementation of electronic hematology consults at a VA hospital. PMID- 26809507 TI - Integrated genome-scale analysis of the transcriptional regulatory landscape in a blood stem/progenitor cell model. AB - Comprehensive study of transcriptional control processes will be required to enhance our understanding of both normal and malignant hematopoiesis. Modern sequencing technologies have revolutionized our ability to generate genome-scale expression and histone modification profiles, transcription factor (TF)-binding maps, and also comprehensive chromatin-looping information. Many of these technologies, however, require large numbers of cells, and therefore cannot be applied to rare hematopoietic stem/progenitor cell (HSPC) populations. The stem cell factor-dependent multipotent progenitor cell line HPC-7 represents a well recognized cell line model for HSPCs. Here we report genome-wide maps for 17 TFs, 3 histone modifications, DNase I hypersensitive sites, and high-resolution promoter-enhancer interactomes in HPC-7 cells. Integrated analysis of these complementary data sets revealed TF occupancy patterns of genomic regions involved in promoter-anchored loops. Moreover, preferential associations between pairs of TFs bound at either ends of chromatin loops led to the identification of 4 previously unrecognized protein-protein interactions between key blood stem cell regulators. All HPC-7 data sets are freely available both through standard repositories and a user-friendly Web interface. Together with previously generated genome-wide data sets, this study integrates HPC-7 data into a genomic resource on par with ENCODE tier 1 cell lines and, importantly, is the only current model with comprehensive genome-scale data that is relevant to HSPC biology. PMID- 26809508 TI - Sprouty 2: a novel attenuator of B-cell receptor and MAPK-Erk signaling in CLL. AB - Clinical heterogeneity is a major barrier to effective treatment of chronic lymphocytic leukemia (CLL). Emerging evidence suggests that constitutive activation of various signaling pathways like mitogen-activated protein kinase extracellular signal-regulated kinase (MAPK-Erk) signaling plays a role in the heterogeneous clinical outcome of CLL patients. In this study, we have investigated the role of Sprouty (SPRY)2 as a negative regulator of receptor and nonreceptor tyrosine kinase signaling in the pathogenesis of CLL. We show that SPRY2 expression is significantly decreased in CLL cells, particularly from poor prognosis patients compared with those from good-prognosis patients. Overexpression of SPRY2 in CLL cells from poor-prognosis patients increased their apoptosis. Conversely, downregulation of SPRY2 in CLL cells from good-prognosis patients resulted in increased proliferation. Furthermore, CLL cells with low SPRY2 expression grew more rapidly in a xenograft model of CLL. Strikingly, B cell-specific transgenic overexpression of spry2 in mice led to a decrease in the frequency of B1 cells, the precursors of CLL cells in rodents. Mechanistically, we show that SPRY2 attenuates the B-cell receptor (BCR) and MAPK-Erk signaling by binding to and antagonizing the activities of RAF1, BRAF, and spleen tyrosine kinase (SYK) in normal B cells and CLL cells. We also show that SPRY2 is targeted by microRNA-21, which in turn leads to increased activity of Syk and Erk in CLL cells. Taken together, these results establish SPRY2 as a critical negative regulator of BCR-mediated MAPK-Erk signaling in CLL, thereby providing one of the molecular mechanisms to explain the clinical heterogeneity of CLL. PMID- 26809509 TI - The effect of multiple primary rules on cancer incidence rates and trends. AB - PURPOSE: An examination of multiple primary cancers can provide insight into the etiologic role of genes, the environment, and prior cancer treatment on a cancer patient's risk of developing a subsequent cancer. Different rules for registering multiple primary cancers (MP) are used by cancer registries throughout the world making data comparisons difficult. METHODS: We evaluated the effect of SEER and IARC/IACR rules on cancer incidence rates and trends using data from the SEER Program. We estimated age-standardized incidence rate (ASIR) and trends (1975 2011) for the top 26 cancer categories using joinpoint regression analysis. RESULTS: ASIRs were higher using SEER compared to IARC/IACR rules for all cancers combined (3 %) and, in rank order, melanoma (9 %), female breast (7 %), urinary bladder (6 %), colon (4 %), kidney and renal pelvis (4 %), oral cavity and pharynx (3 %), lung and bronchus (2 %), and non-Hodgkin lymphoma (2 %). ASIR differences were largest for patients aged 65+ years. Trends were similar using both MP rules with the exception of cancers of the urinary bladder, and kidney and renal pelvis. CONCLUSIONS: The choice of multiple primary coding rules effects incidence rates and trends. Compared to SEER MP coding rules, IARC/IACR rules are less complex, have not changed over time, and report fewer multiple primary cancers, particularly cancers that occur in paired organs, at the same anatomic site and with the same or related histologic type. Cancer registries collecting incidence data using SEER rules may want to consider including incidence rates and trends using IARC/IACR rules to facilitate international data comparisons. PMID- 26809510 TI - Breast and cervical cancer screening among Hispanic subgroups in the USA: estimates from the National Health Interview Survey 2008, 2010, and 2013. AB - PURPOSE: This study examined patterns in mammography and Pap test use across and within subpopulations of Hispanic women. METHODS: Based on data from the National Health Interview Survey (2008, 2010, and 2013), we estimated the proportion of Hispanic women reporting testing for breast and cervical cancer for specific subgroups. We examined test use by demographic characteristics using Chi-square tests. RESULTS: Overall, the proportion of women aged 50-74 years who reported a mammogram within the past 2 years did not differ significantly across Hispanic subgroups. Among publically and uninsured women, however, proportions of mammography utilization varied significantly across Hispanic subgroups. The proportion of women aged 21-65 years who received a Pap test within the past 3 years differed significantly across Hispanic subgroups. CONCLUSIONS: Among subgroups of Hispanic women, patterns in mammography and Pap test use vary by insurance status, length of US residency, and type of screening. Certain subgroups of Hispanic women may benefit from culturally tailored efforts to promote breast and cervical cancer screening. PMID- 26809511 TI - Erratum to: Impact of Chromogranin A deficiency on catecholamine storage, catecholamine granule morphology and chromaffin cell energy metabolism in vivo. PMID- 26809512 TI - Molecular cloning, expression and identification of the promoter regulatory region for the neuropeptide trissin in the nervous system of the silkmoth Bombyx mori. AB - Trissin has recently been identified as a conserved insect neuropeptide, but its cellular expression and function is unknown. We detected the presence of this neuropeptide in the silkworm Bombyx mori using in silico search and molecular cloning. In situ hybridisation was used to examine trissin expression in the entire central nervous system (CNS) and gut of larvae, pupae and adults. Surprisingly, its expression is restricted to only two pairs of small protocerebral interneurons and four to five large neurons in the frontal ganglion (FG). These neurons were further characterised by subsequent multiple staining with selected antibodies against insect neuropeptides. The brain interneurons innervate edges of the mushroom bodies and co-express trissin with myoinhibitory peptides (MIP) and CRF-like diuretic hormones (CRF-DH). In the FG, one pair of neurons co-express trissin with calcitonin-like diuretic hormone (CT-DH), short neuropeptide F (sNPF) and MIP. These neurons innervate the brain tritocerebrum and musculature of the anterior midgut. The other pair of trissin neurons in the FG co-express sNPF and project axons to the tritocerebrum and midgut. We also used the baculovirus expression system to identify the promoter regulatory region of the trissin gene for targeted expression of various molecular markers in these neurons. Dominant expression of trissin in the FG indicates its possible role in the regulation of foregut-midgut contractions and food intake. PMID- 26809514 TI - Position statement on the role of healthcare professionals, patient organizations and industry in European Reference Networks. AB - A call from the EU for the set-up of European Reference Networks (ERNs) is expected to be launched in the first quarter of 2016. ERNs are intended to improve the care for patients with low prevalent or rare diseases throughout the EU by, among other things, facilitating the pooling and exchange of experience and knowledge and the development of protocols and guidelines. In the past, for example where costly orphan drugs have been concerned, industry has played an important role in facilitating consensus meetings and publication of guidelines. The ERNs should provide a unique opportunity for healthcare professionals and patients to lead these activities in an independent way. However, currently costs for networking activities are not to be covered by EU funds and alternative sources of funding are being explored. There is growing concern that any involvement of the industry in the funding of ERNs and their core activities may create a risk of undue influence. To date, the European Commission has not been explicit in how industry will be engaged in ERNs. We believe that public funding and a conflict of interest policy are needed at the level of the ERNs, Centers of Expertise (CEs), healthcare professionals and patient organizations with the aim of maintaining scientific integrity and independence. Specific attention is needed where it concerns the development of clinical practice guidelines. A proposal for a conflict of interest policy is presented, which may support the development of a framework to facilitate collaboration, safeguard professional integrity and to establish and maintain public acceptability and trust among patients, their organizations and the general public. PMID- 26809515 TI - Research on structures, mechanical properties, and mechanical responses of TKX-50 and TKX-50 based PBX with molecular dynamics. AB - To improve the practicality and safety of a novel explosive dihydroxylamm onium 5,5'-bis (tetrazole)-1,1'-diolate (TKX-50), polyvinylidene difluoride (PVDF) and polychlorotrifluoroe-thylene (PCTFE) were respectively added to the TKX-50, forming the polymer-bonded explosives (PBX). Interfacial and mechanical properties of PBX were investigated through molecular dynamics (MD) method, desensitizing mechanisms of fluorine-polymers for TKX-50 were researched by compression and bulk shear simulations. Results show that the binding energies (E bind ) between polymers (PVDF or PCTFE) and TKX-50 surfaces all rank in order of (011) > (100) > (010), shorter interatomic distance and the resulted higher potentials lead to higher E bind on TKX-50/PVDF interfaces than that on PCTFE/TKX 50 interfaces. Compared with TKX-50, the ductility of PBX is improved due to the isotropic mechanical property and flexibility of fluorine-polymers especially the PCTFE. Desensitizing effect of fluorine-polymers for TKX-50 is found under loading condition, which is attributed to the enhanced compressibility and buffer capacity against external pressure in compression, as well as the improved lubricity to reduce the sliding potentials in bulk shear process. Graphical Abstract Comparisons of the internal stress and slide potentials of the novel explosive,TKX-50 and its based PBX. Desensitizing effects can be found by the adding of fluorine-polymers, it owes to their better flexibility and lubricity as well as the amorphous nature. PMID- 26809517 TI - Psychosocial Quality-of-Life, Lifestyle and Adiposity: A Longitudinal Study in Pre-schoolers (Ballabeina Study). AB - PURPOSE: In obesity prevention, understanding psychosocial influences in early life is pivotal. Reviews reported contradictory results and a lack of longitudinal studies focusing on underlying lifestyle factors. This study tested whether psychosocial Quality-Of-Life (QOL) was associated with pre-schoolers' lifestyle and adiposity changes over one school year and whether lifestyle moderated the latter. It was hypothesised that QOL might not impact adiposity in everybody but that this might depend on preceding lifestyle. METHOD: Longitudinal data from 291 Swiss pre-schoolers (initially 3.9-6.3 years) was available. The following measures were used in longitudinal regressions: psychosocial QOL by PedsQL, adiposity (BMI z-score, waist, fat%), diet (food frequency), sedentary time and accelerometer-based activity. RESULTS: Concerning lifestyle, low psychosocial QOL was only related to unfavourable changes in diet (less fruit beta = 0.21 and more fat intake beta = -0.28) and lower physical activity (beta = 0.21). Longitudinal QOL-adiposity relations appeared only after moderation by lifestyle factors (beta-range 0.13-0.67). Low psychosocial QOL was associated with increased adiposity in children with an unhealthy diet intake or high sedentary time. By contrast, low psychosocial QOL was associated with decreasing adiposity in high fruit consumers or more physically active pre-schoolers. CONCLUSION: Results emphasise the need for testing moderation in the QOL adiposity relation. An unhealthy diet can be a vulnerability factor and high physical activity a protective factor in QOL-related adiposity. Consequently, QOL and lifestyle should be targeted concurrently in multi-factorial obesity prevention. The environment should be an 'activity encouraging, healthy food zone' that minimises opportunities for stress-induced eating. In addition, appropriate stress coping skills should be acquired. PMID- 26809520 TI - [Update on Cancer Epidemiology in Japan]. AB - Accumulated epidemiological evidence has revealed several risk and preventive factors for cancer. Thus, cancer prevention guidelines for the Japanese population have been developed on the basis of scientific evidence from mainly studies conducted in Japan. In Japan, tobacco smoking and infections are the major causes of cancer. Further control of these factors will contribute to substantial reductions in cancer incidence and mortality in Japan. Concurrently, large-scale molecular epidemiologic studies are ongoing in order to obtain epidemiological evidence for personalized prevention strategies. In particular, evidence from omics analyses and investigation of gene-environment interactions may contribute to the further understanding of the biological mechanism underlying cancer occurrence. In addition, the establishment of preventive measures according to individual disease risk, on the basis of risk prediction models including omics data, is necessary. PMID- 26809519 TI - Reorganization of a synthetic microbial consortium for one-step vitamin C fermentation. AB - BACKGROUND: In the industry, the conventional two-step fermentation method was used to produce 2-keto-L-gulonic acid (2-KGA), the precursor of vitamin C, by three strains, namely, Gluconobacter oxydans, Bacillus spp. and Ketogulonicigenium vulgare. Despite its high production efficiency, the long incubation period and an additional second sterilization process inhibit the further development. Therefore, we aimed to reorganize a synthetic consortium of G. oxydans and K. vulgare for one-step fermentation of 2-KGA and enhance the symbiotic interaction between microorganisms to perform better. RESULTS: During the fermentation, competition for sorbose of G. oxydans arose when co-cultured with K. vulgare. In this study, the competition between the two microbes was alleviated and their mutualism was enhanced by deleting genes involved in sorbose metabolism of G. oxydans. In the engineered synthetic consortium (H6 + Kv), the yield of 2-KGA (mol/mol) against D-sorbitol reached 89.7 % within 36 h, increased by 29.6 %. Furthermore, metabolomic analysis was used to verify the enhancement of the symbiotic relationship and to provide us potential strategies for improving the synthetic consortium. Additionally, a significant redistribution of metabolism occurred by co-culturing the K. vulgare with the engineered G. oxydans, mainly reflected in the increased TCA cycle, purine, and fatty acid metabolism. CONCLUSIONS: We reorganized and optimized a synthetic consortium of G. oxydans and K. vulgare to produce 2-KGA directly from D-sorbitol. The yield of 2-KGA was comparable to that of the conventional two-step fermentation. The metabolic interaction between the strains was further investigated by metabolomics, which verified the enhancement of the mutualism between the microbes and gave us a better understanding of the synthetic consortium. PMID- 26809521 TI - [Antitumor Molecular Mechanism of Trifluridine and Tipiracil Hydrochloride (TAS 102: TFTD)]. AB - Treatment options for patients with metastatic colorectal cancer (mCRC), who are refractory to standard chemotherapy, are limited. In a global multicenter randomized double-blind phase III study (RECOURSE study), TAS-102 (TFTD) administration significantly improved overall survival rate with favorable safety profile in mCRC patients refractory to standard chemotherapy (HR=0.68, p<0.001). TFTD was approved initially in Japan in March 2014 and is currently under review by health authorities in the United States and Europe. TFTD is expected to play an important role in salvage-line treatment for patients with mCRC. In this review, we present the history of its clinical development and the experimental data that elucidate the underlying molecular mechanism of action of TFTD and its key component, trifluridine. PMID- 26809522 TI - [Recent Advances in Systemic Chemotherapy for Metastatic Colorectal Cancer]. AB - The recent development of chemotherapeutic agents and biomarkers have remarkably improved treatment outcomes of metastatic colorectal cancer (mCRC). However, decision making regarding the choice of therapy for mCRC has been complicated by the availability of many different treatment options. In this review, we will discuss the clinical evidence for current systemic treatment, including the key roles of 3 cytotoxic drugs and oral fluoropyrimidines, the appropriate use of anti-VEGF and anti-EGFR therapy, the significance of RAS mutation status as a predictive marker for anti-EGFR therapy, and new agents for salvage therapy (regorafenib and TAS-102 [TFTD]). PMID- 26809523 TI - [Roles of Histopathological Diagnosis in Multidisciplinary Therapy for Soft Tissue Sarcoma]. AB - Soft-tissue sarcoma (STS) is very rare malignant tumor with many kinds of histological subtypes and variants, as well as being a newly emerging entity. Because of its rarity, general pathologists are not familiar with STS and have difficulty making an accurate histopathological diagnosis in such cases. As an accurate diagnosis is essential for the selection of appropriate therapy, the Japanese Society of Pathology offers a nationwide consultation system. Some clinical trials for molecular targeted therapy have been conducted based on pathological examination findings. Pathologists play various roles in the future of sarcoma therapy. PMID- 26809524 TI - [Medication Therapy for Soft Tissue Sarcoma (Current Status and Future Perspective)]. AB - Doxorubicin and ifosfamide have played a major role in the medical therapy for soft tissue sarcoma (STS). In the last few years, new cytotoxic drugs (eribulin, trabectedin, etc.) and molecular targeting drugs(pazopanib, which is a tyrosine kinase inhibitor of VEGFR1-3, and PDGFR) have been introduced in clinical practice for the treatment of STS. These new drugs are expected to improve the outcome of medical therapy for STS in the future. PMID- 26809525 TI - [Treatments of Soft Tissue Sarcomas by Orthopaedic Surgeons in Japan]. AB - In Japan, the treatment of soft tissue sarcomas (STS) has been performed mainly by orthopaedic surgeons. The standard therapy for all cases of STS is surgical resection of the tumor. The prognosis of patients with unresectable tumors or distant metastases is poor despite treatment with intensive chemotherapy. Adjuvant chemotherapy is indicated for patients with resectable tumors. Round cell STS, including extraskeletal Ewing sarcoma and rhabdomyosarcoma, have high sensitivity to chemotherapy. The standard treatment for round-cell STS is multimodal therapy with surgery and chemotherapy, with or without radiotherapy. On the other hand, non-round cell STS, including leiomyosarcoma, synovial sarcoma, and liposarcoma, have low sensitivity to chemotherapy. Thus, the standard treatment for non-round cell STS is essentially, surgery. Large and high grade non-round cell STS are also treated using adjuvant chemotherapy along with surgery. In this review, the standard therapies for STS and the future perspective in Japan are discussed. PMID- 26809526 TI - [Radiation Therapy for Management of Soft Tissue Sarcomas]. AB - Soft tissue sarcomas (STS) are rare malignancies. STS represent a heterogeneous group of tumors, with many of them posing a high risk of local recurrence and distant metastasis. The major therapeutic goals of treating STS are to maximize local tumor control using minimal surgery and to improve survival. The ability of radiation therapy (RT) to improve local control has made it a cornerstone in the multimodality treatment of STS. Koshy reported survival benefit of RT in patients undergoing limbsparing surgery for soft tissue sarcomas of the extremities. A retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database that included data from 6,960 patients. They reports that radiation was associated with improved survival in patients with high-grade tumors. The randomized study of preoperative versus postoperative radiation therapy conducted by the National Cancer Institute of Canada (NCIC). The radiation therapy techniques consisted of 50 Gy in the preoperative setting and 66 Gy given postoperatively. Patients treated with postoperative radiation therapy tended to have greater fibrosis. Fibrosis, joint stiffness and edema adversely affect patient function. Haas reported the proposed consensus guidelines on target volume delineation with RT for STS in 2012. Particle therapy, intensity-modulated RT (IMRT) and image-guided RT (IGRT) offers the opportunity to reduce the normal tissue morbidity of RT while maintaining local tumor control. In conclusion, the precision with which the radiation dose is distributed with advanced RT has a beneficial effect in sparing normal tissue with improved local control over that achieved with conventional RT. PMID- 26809527 TI - [Evaluation of Drug Interaction between S-1 and Warfarin]. AB - Prolonged prothrombin time is observed in patients taking warfarin (WF) with a fluoropyrimidine, such as S-1. When WF is combined with S-1, the prothrombin time international normalized ratio (PT-INR) and dose adjustment of WF should be closely monitored. To date, no clinical data have been reported in terms of the relation between temporal variation of PT-INR and its therapeutic range. In this study, we retrospectively collected patients' clinical data including PT-INR. We identified 21 patients receiving WF therapy before the start of S-1 treatment. Patient characteristics were male/female: 18/3, median age: 69 (range 48-81) years old, cancer of gastric/lung/pancreatic/other: 8/5/4/4, and history of deep vein thrombosis (DVT)/atrial fibrillation (AF)/cerebral infarction (CI)/other: 11/6/2/2. The PT-INR of 16 patients exceeded normal upper limits after taking S-1 with WF. The median time to exceed the PT-INR upper therapeutic range is 25 (range 3-77) days. Patients receiving WF anticoagulant therapy concomitant with S 1 should have their PT-INR closely monitored and WF doses adjusted accordingly. PMID- 26809528 TI - [Study of the Postoperative Adjuvant Chemotherapy with UFT/LV or Capecitabine for Stage III Colorectal Cancer]. AB - OBJECTIVE: This study sought to compare UFT/LV with capecitabine as adjuvant chemotherapy for the treatment of stage III colorectal cancer. METHODS: We conducted a retrospective analysis of patients with Stage III colorectal cancer who underwent surgical resection, except low rectal resections (Rb), followed by adjuvant chemotherapy with UFT/LV or capecitabine between 2007 and 2009, and evaluated background factors, adverse event profiles, disease free survival (DFS), and overall survival (OS). RESULTS: The analysis included 39 patients treated with UFT/LV and 29 with capecitabine, with no significant differences observed between the groups in terms of gender, age, or disease Stage. The most common adverse events were gastrointestinal symptoms in the UFT/LV group, and hand-foot syndrome in the capecitabine group. The 3-year DFS was 69.2 and 64.7% in the UFT/LV and capecitabine groups respectively, and 3-year OS was 89.7 and 92.7% in the UFT/LV and capecitabine groups respectively, indicating no significant differences between the groups. CONCLUSION: There were no marked differences in treatment outcomes with UFT/LV or capecitabine when they were used as adjuvant chemotherapy for Stage III colorectal cancer, suggesting that a choice between these 2 agents can be made on the basis of avoiding adverse events. PMID- 26809529 TI - [Hepatic Arterial Infusion Chemotherapy Using a Reservoir for Advanced Hepatocellular Carcinoma]. AB - Administration of chemotherapy treating hepatocellular carcinoma (HCC) is divided into hepatic arterial infusion chemotherapy (HAIC) which delivers chemotherapeutic agents directly using a catheter, and systemic chemotherapy including oral treatment. Evidence for treatment with sorafenib has emerged indicating it is an effective drug for advanced HCC. HAIC can provide high anticancer efficacy, and it is often performed on patients with advanced HCC in our country. Since various HAIC regimens exist, the efficacy of HAIC using a reservoir system was tested in patients with advanced HCC. The overall response rate was 36%, with a median survival time of 11.9 months. Patients with controlled disease at 8 weeks had Child-Pugh classification A, and no increase in AFP levels when starting early stage in treatment, which were considered to be factors that influenced therapeutic efficacy. Comparison with other HAIC regimens, and consideration of combined treatments using sorafenib and HAIC will be needed. PMID- 26809530 TI - [The Importance of Medication History Management by Hospital and Community Pharmacists for Oral Anticancer Drug S-1(Tegafur/Gimeracil/Oteracil Potassium)--A Retrospective Study]. AB - S-1 (tegafur/gimeracil/oteracil potassium) is an effective oral anticancer drug for treatment of a wide spectrum of cancers. However, it may incur serious adverse effects through factors such as interactions with other drugs, renal dysfunction, or an insufficient washout period. In view of this, pharmacists should play an increasingly significant role in managing the medication history of patients treated with S-1. As there seems to be no standardized management tool for patients receiving S-1, we conducted a retrospective study to evaluate medication history management methods, which are commonly available in community pharmacies as well as hospitals. We identified 128 outpatients who were prescribed S-1 for the first time at the National Cancer Center Hospital from July to December of 2011. These patients were divided into in-hospital (n=48) and out-of-hospital (n=80) groups. The percentage of patients, who dropped out during the first course of S-1 treatment, was 16.7% for the in-hospital group, and 10% for the out-of-hospital group. Examining renal dysfunction, non-elderly patients with low creatinine clearance (Ccr) were found. These results suggest that there is the possibility of side effect occurrence in both the in-hospital and out-of hospital prescription groups. Community pharmacists should check prescriptions with particular attention to the Ccr. It is necessary to develop mechanisms for cooperation between hospital and community pharmacists, with clear role sharing between them, allowing the community pharmacists to exercise medication history management for patients prescribed S-1 to the same degree as hospital pharmacists based on available information including laboratory test values. PMID- 26809531 TI - Development of Support System for Breast Cancer Patients--Managing Side Effects through an Internet-Based System. AB - Chemotherapy in the outpatient setting is effective in improving patients' quality of life (QOL). However, the increasing availability of targeted molecular agents in addition to conventional anti-cancer medications has placed increased importance on managing adverse events and educating patients about side effects that can affect their QOL. We developed an Internet-based "Patient Support System"to enable patients at home to communicate symptoms of side effects and administration status to a hospital interface that documents and monitors the ongoing side-effect profile. In a trial of 8 patients scheduled to receive chemotherapy before or after surgery, our system enabled medical staff to quantitatively confirm data on side effects recorded daily by the outpatients, demonstrating that it functions effectively in maintaining the patient's QOL. Moreover, it clearly identified significant differences in the occurrence and status of side effects between patients receiving the same anticancer medication. Patients reported that the onset of side effects and recovery status could be confirmed objectively, thus enabling self-management of the disease, which helped greatly in managing side effects and schedules throughout the treatment period. This system has potential as a supportive tool for activities of daily living while maintaining QOL and improving the overall therapeutic effect. PMID- 26809532 TI - [Successful Treatment of Non-Small Cell Lung Cancer with Afatinib after Gefitinib Induced Hepatotoxicity]. AB - A 71-year-old man was referred to our hospital for treatment of non-small-cell lung cancer (adenocarcinoma of the lungs, with multiple bone metastases, cT1bN0M1b, harboring an EGFR mutation [exon 19 deletion]). Gefitinib was administered as daily oral doses of 250 mg. After 18 days, gefitinib was discontinued because of hepatotoxicity (Grade 3). Forty days later, afatinib was administered as daily oral doses of 40 mg. Within 1 year, the primary tumor and bone metastases achieved a partial response without hepatotoxicity. We suggest that afatinib is an effective and well-tolerated treatment option for patients with hepatotoxicity under gefitinib treatment. PMID- 26809533 TI - [A Case of Multiple Bevacizumab-Related Colonic Perforations during Opioid Use]. AB - We present the case ofa 54-year-old man who had been treated with bevacizumab containing chemotherapy for a postoperative recurrence of lung cancer for 5 months; he had used opioids for cancer pain in his right lateral chest for 2 months. He was admitted to the hospital because his chest pain had worsened 5 days earlier and he was experiencing a dull pain in his lower abdomen. His condition was recognized as an aggravation of the cancer pain and his opioid dose was increased. He presented with intense abdominal pain 6 days after admission, and we diagnosed gastrointestinal perforations from an abdominal CT scan. Therefore, we undertook an emergency operation. Multiple perforations were seen on the transverse and descending colon; an extensive colectomy and a colostomy were performed. Histopathological findings showed that multiple ulcer perforations and normal mucosa coexisted throughout the resected specimen. Bevacizumab-induced ischemic changes were the suspected cause. When pain control becomes variable during opioid use, conditions such as bevacizumab-related gastrointestinal perforations should be considered, in addition to progression of the cancer pain itself, and the appropriate treatment should be administered. PMID- 26809534 TI - [A Case of Small Cell Lung Cancer Treated with Concurrent Chemoradiotherapy with Carboplatin plus Etoposide in a Hemodialysis Patient]. AB - In recent years, many patients have had to undergo hemodialysis due to chronic renal failure. In addition, the number of hemodialysis patients in whom lung cancer is discovered is increasing. However, a standard chemoradiotherapy regimen for limited-disease small-cell lung cancer patients undergoing maintenance hemodialysis has not yet been established. We administered concurrent chemoradiotherapy using carboplatin 300 mg/m2 (day 1) plus etoposide 50 mg/m2 (day 1, 3). A partial response was achieved after 4 courses of chemotherapy and 68 Gy of radiotherapy. The major toxicities were hematological toxicities; they included grade 4 thrombocytopenia, grade 3 anemia, and neutropenia. PMID- 26809535 TI - [A Case of Disseminated Bone Marrow Carcinomatosis Arising from Breast Cancer for Which Paclitaxel and Bevacizumab Treatment Was Effective]. AB - A 42-year-old woman visited our hospital with high fever and general malaise. A CT examination revealed that she had carcinoma of the left breast with axillary lymph node metastases and multiple bone metastases. A blood test showed anemia, thrombopenia and the existence of blast-like cells. Adenocarcinoma cells were detected in a bone marrow aspiration specimen, and the patient was diagnosed with disseminated carcinomatosis of the bone marrow. Systemic chemotherapy with paclitaxel plus bevacizumab was initiated while a blood transfusion was performed. Her symptoms improved, and the blood test results normalized. Disseminated carcinomatosis of the bone marrow is reported to have a poor prognosis, but paclitaxel plus bevacizumab is a possible effective chemotherapy. PMID- 26809536 TI - [Treatment Strategy for Non-Functional Pancreatic Neuroendocrine Tumors (P-NETs) at Kurume University Hospital]. AB - Pancreatic neuroendocrine tumors (P-NETs) are relatively rare. Approximately 50 90% of non-functioning P-NETs are malignant, and the only curative treatment is surgical resection. Liver and lymph node metastases often occur. In Japan, the mTOR inhibitor everolimus is now covered by the national health insurance for treatment of P-NETs, including advanced and unresectable tumors. We present a case of P-NETs with liver metastases seen at our hospital and discuss our treatment strategy for this disease. Patients with tumors<=1 cm receive follow-up observation. For G1 and G2 (other than G3) tumors, if their size is >1 cm when first discovered, resection of the primary lesion along with lymph node dissection (as for pancreatic cancer) is performed. In G1 and G2 tumors with synchronous distant metastases, the primary lesion is first resected, and depending on the pathological findings, chemotherapy (LAR plus everolimus) may be administered. After 4 courses of chemotherapy, the response is assessed, and if further resection is possible, resection is performed. When there are synchronous liver metastases, if partial resection and local treatment (such as RFA) are possible, the primary lesion and synchronous lesions are resected. If a major hepatic resection procedure such as a segmentectomy or lobectomy is possible, the primary lesion is resected, followed by chemotherapy. After 4 courses of chemotherapy, the response is assessed, and if further resection is possible, hepatic resection is performed. G3 tumors are usually highly malignant, advanced, and often associated with metastases at the time of diagnosis. Chemotherapy may be an option for treating patients with G3 tumors. PMID- 26809537 TI - [A Case of Recurrent Gallbladder Cancer with a Complete Response to S-1 Alternate Day Administration]. AB - An 86-year-old woman underwent a cholecystectomy for gallbladder cancer. Seven months later, an abdominal CT scan showed multiple liver and lymph node metastases. Treatment with S-1 was started at a dose of 100 mg/day, but was changed to alternate-day administration because of diarrhea. Metastatic lesions showed a complete response after 7 months of chemotherapy. S-1 alternate-day therapy could be maintained without any severe adverse events. This method can be managed safely and with certainty in an elderly patient and it has demonstrated efficacy in the treatment of recurrent gallbladder cancer. PMID- 26809538 TI - [A Case of Advanced Gastric Cancer with a Complete Response to S-1 Neoadjuvant Chemotherapy in an Elderly Patient]. AB - We report a case of advanced gastric cancer that responded completely to S-1 neoadjuvant chemotherapy. An 80-year-old female complained of nausea. A gastroscopy and CT scan revealed advanced gastric cancer with lymph node metastasis (cT4b [diaphragm], cN3a, cM0, cStage III C). S-1 (100 mg/body/day) was administered orally for 14 consecutive days followed by a 7-day interval. After 2 courses of monotherapy, we conducted a total gastrectomy with D2 lymph node dissection. Histological findings revealed that there were no cancer cells in either the primary tumor or the lymph nodes. This meant that the resected lesions were pathologic Grade 3. Our report suggests that S-1 may have a potent therapeutic effect as a neoadjuvant chemotherapy for advanced gastric cancer especially in older patients. PMID- 26809539 TI - [A Case of Long-Term Survival in a Patient with Small Intestinal Adenocarcinoma with Peritoneal Dissemination]. AB - Primary small intestinal adenocarcinoma is rare and its outcome is poor. A 46 year-old man admitted for vomiting was found in enhanced abdominal CT to have local jejunum stenosis and dilation at its oral site. A partial jejunectomy was performed and a jejunal tumor with multiple disseminated nodules in the peritoneum was revealed. Histologically, the adenocarcinoma of the jejunum appeared to be a papillary adenocarcinoma, and also, in part, a moderately differentiated tubular adenocarcinoma. After the jejunectomy, the patient was treated with S-1 chemotherapy, but 22 months after the initial diagnosis, a recurrence was detected. The patient underwent a second partial jejunectomy, and a weekly dose of paclitaxel (PTX) plus doxifluridine (5'-DFUR) was selected as the second-line treatment. The patient is still responding to the treatment 55 months after the last operation. Combination chemotherapy with weekly PTX/5'-DFUR may improve the prognosis for S-1-resistant small intestinal adenocarcinoma. PMID- 26809540 TI - [A Case of Liver Metastasis of Descending Colon Cancer with a Pathological Complete Response to mFOLFOX6]. AB - A 75-year-old woman presented with right upper quadrant abdominal pain and anorexia. She was diagnosed with descending colon cancer with lymph node and liver metastases. She was treated with preoperative chemotherapy consisting of levofolinate/5-fluorouracil/oxaliplatin (mFOLFOX6). After the completion of 7 courses of chemotherapy, the tumor shrunk remarkably. A left-sided colectomy with radical lymphadenectomy and an extensive posterior segment resection of the liver were performed. Postoperatively, pathological analysis revealed no cancerous cells in the primary tumor, lymph node metastases, or liver metastases. She is currently receiving mFOLFOX6 therapy as adjuvant chemotherapy. In a patient with advanced colon cancer, a complete response of not only the primary tumor but also the lymph node and liver metastases to preoperative chemotherapy is rare. This case demonstrates that mFOLFOX6 therapy is safe and effective as preoperative chemotherapy for advanced colon cancer. PMID- 26809541 TI - [A Case of Descending Colon Adenocarcinoma with Neuroendocrine Differentiation Successfully Treated with FOLFIRI plus Bevacizumab]. AB - We report a case of descending colon adenocarcinoma with neuroendocrine differentiation that was effectively treated with FOLFIRI plus bevacizumab. A 70 year-old man underwent a colonoscopy and was found to have a type 2 tumor of the descending colon. A well-to-moderately differentiated adenocarcinoma was diagnosed by biopsy. A preoperative CT scan showed paraaortic lymph node and liver metastasis, and that the tumor was directly invading the spleen. The patient underwent a left hemicolectomy with resection of the pancreas tail, spleen, and diaphragm. The pathological diagnosis was adenocarcinoma with less than 30% neuroendocrine differentiation in the primary tumor and almost 100% neuroendocrine differentiation in the metastatic lymph nodes. After surgery, FOLFIRI plus bevacizumab treatment was initiated. After 33 treatment cycles, the paraaortic lymph node and liver metastasis disappeared and the patient has remained progression-free to date. Adenocarcinoma with neuroendocrine differentiation of the colon is rare and an effective chemotherapy has not yet been established. We report this case with a review of the literature. PMID- 26809542 TI - [A Case of Thrombotic Thrombocytopenic Purpura in a Patient Undergoing FOLFOX6 plus Panitumumab Therapy for Unresectable Recurrent Rectal Cancer with a Rapidly Progressive Course]. AB - A 71-year-old male patient began FOLFOX6 plus panitumumab treatment for unresectable recurrent rectal cancer. He developed thrombocytopenia after 2 courses of treatment and therefore a platelet transfusion was performed. The day after transfusion, the patient developed jaundice and hematuria. His lactate dehydrogenase levels had increased and a peripheral blood smear review revealed the presence of schistocytes. Anti-ADAMTS13 antibodies were present, and there was a reduction in ADAMTS13 activity. The patient was diagnosed with thrombotic thrombocytopenic purpura and treated with a plasma exchange. The day after the plasma exchange, his clinical condition rapidly worsened and he died. Thrombocytopenia due to chemotherapy often appears as myelosuppression. If conditions such as jaundice, indirect bilirubinemia, or hematuria appear during the course of chemotherapy, this condition must be considered as a differential diagnosis. PMID- 26809544 TI - Integrative genomic and proteomic analyses identifies glycerol-3-phosphate acyltransferase as a target of low-dose ionizing radiation in EBV infected-B cells. AB - PURPOSE: We sought to gain a better understanding of the low-dose ionizing radiation (LDIR)-induced molecular changes in transformed pre-malignant cells in their microenvironment. MATERIALS AND METHODS: The cellular response to LDIR was compared and contrasted using immortalized human Epstein-Barr virus-infected B cells (EBV-B) in mono-culture, co-culture with human bone marrow derived stromal cells (MSC), or under the LDIR-induced bystander effect. The resulting alterations in protein and gene expression (including microRNA, miRNA) were evaluated by isobaric tags for relative and absolute quantification (iTRAQ) proteomics assay, western blot, cDNA array and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. RESULTS: The miRNAs let7a, miR 15b, miR-16, and miR-21, and a lipid metabolic miRNA hub miR-23b, were upregulated after LDIR exposure in the mono-cultured EBV-B cells, but were downregulated in EBV-B cells co-irradiated with MSC. A lipid biosynthesis enzyme glycerol-3-phosphate acyltransferase, the common target of these miRNA, was downregulated at the level of protein and mRNA expression in the LDIR-exposed, mono-cultured EBV-B cells and upregulated MSC co-cultured EBV-B cells. CONCLUSIONS: These results suggest a putative miRNA regulatory mechanism controlling the LDIR-induced stress response, and illustrate that LDIR exposure, and the cell's microenvironment, can affect specific gene expression, both directly and indirectly, resulting in altered protein expression. PMID- 26809546 TI - Haemophilia in a real-world setting: the value of clinical experience in data collection. AB - At the 8th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) held in Helsinki, Finland, in February 2015, Pfizer sponsored a satellite symposium entitled: 'Haemophilia in a real-world setting: The value of clinical experience in data collection' Co-chaired by Riitta Lassila (Helsinki University Central Hospital, Helsinki, Finland) and Gerry Dolan (Guy's and St Thomas' Hospital, London, UK); the symposium provided an opportunity to explore the practical value of real-world data in informing clinical decision-making. Gerry Dolan provided an introduction to the symposium by describing what is meant by real-world data (RWD), stressing the role RWD can play in optimising patient outcomes in haemophilia and highlighting the responsibility of all stakeholders to collaborate in continuous data collection. Kristian Juusola (Oulu University Hospital, Oulu, Finland) then provided personal experience as a haemophilia nurse around patient views on adherence to treatment regimes, and how collecting insights into real-world use of treatment can shape approaches to improving adherence. The importance of elucidating pharmacokinetic parameters in a real world setting was then explored by Vuokko Jokela (Helsinki University, Helsinki, Finland). Finally, Alfonso Iorio (McMaster University, Hamilton, Ontario, Canada) highlighted the importance of quality data collection in translating clinical reality into scientific advances. PMID- 26809547 TI - Comparison of Ischemic and Nonischemic Bowel Segments in Patients With Mesenteric Ischemia: Multidetector Row Computed Tomography Findings and Measurement of Bowel Wall Attenuation Changes. AB - OBJECTIVE: To describe multidetector row computed tomography (MDCT) findings and to compare the enhancing ratio of ischemic and nonischemic bowel wall segments in patients with mesenteric ischemia. PATIENTS AND METHODS: We performed a retrospective review of 69 patients with pathologically proven mesenteric ischemia who underwent a preoperative MDCT evaluation from January 1, 2010, through December 31, 2014. Two reviewers performed quantitative MDCT measurements of the bowel wall attenuation of the ischemic and nonischemic bowel segments on the unenhanced phase, arterial phase, and portal venous phase. Receiver operating characteristic curves for the enhancing ratios on the arterial phase and portal venous phase (ERv) were calculated to discriminate the 2 segments. A concordance correlation coefficient was used to assess interobserver variability. RESULTS: The most common origin of ischemia was the mesenteric artery (45 of the 69 patients [65.2%]), but only 5 patients (7.2%) had evidence of arterial thrombus on MDCT. The quantitative MDCT measurements indicated that the ischemic bowel segments had significantly less bowel wall attenuation than the nonischemic bowel segments on the arterial phase (28.58+/-9.28 vs 58.97+/-12.50; P<.001) and the portal venous phase (33.93+/-11.16 vs 76.25+/-13.56; P<.001). The enhancing ratio on the arterial phase (cutoff, 0.32 or less; sensitivity, 89.9%; specificity, 98.6%) and the ERv (cutoff, 0.81 or less; sensitivity, 95.7%; specificity, 98.6%) predicted bowel ischemia. The most common MDCT findings in ischemic bowel were thickened bowel wall in 59 patients (85.5%), mesenteric fatty stranding in 57 (82.6%), and decreased bowel wall enhancement in 56 (81.2%). All quantitative measurements reached moderate to substantial agreement (0.399-0.601). CONCLUSION: Without oral contrast administration and at a constant 120-peak kilovolt setting, MDCT findings of decreased enhancement of the thickened bowel wall together with a low ERv value predicted the presence of an ischemic bowel segment. PMID- 26809548 TI - Biomass-derived carbonaceous positive electrodes for sustainable lithium-ion storage. AB - Biomass derived carbon materials have been widely used as electrode materials; however, in most cases, only electrical double layer capacitance (EDLC) is utilized and therefore, only low energy density can be achieved. Herein, we report on redox-active carbon spheres that can be simply synthesized from earth abundant glucose via a hydrothermal process. These carbon spheres exhibit a specific capacity of ~210 mA h gCS(-1), with high redox potentials in the voltage range of 2.2-3.7 V vs. Li, when used as positive electrode in lithium cells. Free standing, flexible composite films consisting of the carbon spheres and few walled carbon nanotubes deliver high specific capacities up to ~155 mA h gelectrode(-1) with no obvious capacity fading up to 10,000 cycles, proposing to be promising positive electrodes for lithium-ion batteries or capacitors. Furthermore, considering that the carbon spheres were obtained in an aqueous glucose solution and no toxic or hazardous reagents were used, this process opens up a green and sustainable method for designing high performance, environmentally friendly energy storage devices. PMID- 26809554 TI - Tau aggregation inhibitors: the future of Alzheimer's pharmacotherapy? PMID- 26809555 TI - Project Energize: intervention development and 10 years of progress in preventing childhood obesity. AB - Prevention of childhood obesity is a global priority. The school setting offers access to large numbers of children and the ability to provide supportive environments for quality physical activity and nutrition. This article describes Project Energize, a through-school physical activity and nutrition programme that celebrated its 10-year anniversary in 2015 so that it might serve as a model for similar practices, initiatives and policies elsewhere. The programme was envisaged and financed by the Waikato District Health Board of New Zealand in 2004 and delivered by Sport Waikato to 124 primary schools as a randomised controlled trial from 2005 to 2006. The programme has since expanded to include all 242 primary schools in the Waikato region and 70 schools in other regions, including 53,000 children. Ongoing evaluation and development of Project Energize has shown it to be sustainable (ongoing for >10 years), both effective (lower obesity, higher physical fitness) and cost effective (one health related cost quality adjusted life year between $18,000 and $30,000) and efficient ($45/child/year) as a childhood 'health' programme. The programme's unique community-based approach is inclusive of all children, serving a population that is 42% Maori, the indigenous people of New Zealand. While the original nine healthy eating and seven quality physical activity goals have not changed, the delivery and assessment processes has been refined and the health service adapted over the 10 years of the programme existence, as well as adapted over time to other settings including early childhood education and schools in Cork in Ireland. Evaluation and research associated with the programme delivery and outcomes are ongoing. The dissemination of findings to politicians and collaboration with other service providers are both regarded as priorities. PMID- 26809557 TI - Toxic Plant Atlas. PMID- 26809558 TI - Mg chelatase in chlorophyll synthesis and retrograde signaling in Chlamydomonas reinhardtii: CHLI2 cannot substitute for CHLI1. AB - The oligomeric Mg chelatase (MgCh), consisting of the subunits CHLH, CHLI, and CHLD, is located at the central site of chlorophyll synthesis, but is also thought to have an additional function in regulatory feedback control of the tetrapyrrole biosynthesis pathway and in chloroplast retrograde signaling. In Arabidopsis thaliana and Chlamydomonas reinhardtii, two genes have been proposed to encode the CHLI subunit of MgCh. While the role of CHLI1 in A. thaliana MgCh has been substantially elucidated, different reports provide inconsistent results with regard to the function of CHLI2 in Mg chelation and retrograde signaling. In the present report, the possible functions of both isoforms were analyzed in C. reinhardtii Knockout of the CHLI1 gene resulted in complete loss of MgCh activity, absence of chlorophyll, acute light sensitivity, and, as a consequence, down-regulation of tetrapyrrole biosynthesis and photosynthesis-associated nuclear genes. These observations indicate a phenotypical resemblance of chli1 to the chlh and chld C. reinhardtii mutants previously reported. The key role of CHLI1 for MgCh reaction in comparison with the second isoform was confirmed by the rescue of chli1 with genomic CHLI1 Because CHLI2 in C. reinhardtii shows lower expression than CHLI1, strains overexpressing CHLI2 were produced in the chli1 background. However, no complementation of the chli1 phenotype was observed. Silencing of CHLI2 in the wild-type background did not result in any changes in the accumulation of tetrapyrrole intermediates or of chlorophyll. The results suggest that, unlike in A. thaliana, changes in CHLI2 content observed in the present studies do not affect formation and activity of MgCh in C. reinhardtii. PMID- 26809559 TI - Genital Epstein Barr Virus is associated with higher prevalence and persistence of anal human papillomavirus in HIV-infected men on antiretroviral therapy. AB - BACKGROUND: Epstein Barr virus (EBV) and human papillomavirus (HPV) can co-exist in pharyngeal and cervical malignancies. However, the natural history and factors associated with persistent HPV infection among HIV-infected men who have sex with men (MSM) are unclear. METHODS: 131 HIV-infected MSM were followed for 48 weeks and screened for multiple co-infections, including seminal EBV DNA and high risk (HR)-HPV messenger RNA (mRNA) at several sites (semen, anal, pharynx). Primary analysis tested if seminal EBV shedding was associated with increased prevalence of HR-HPV at baseline using univariate tests and multivariable logistic regression. In participants with detectable anal HR-HPV at baseline, we tested if presence of seminal EBV shedding at baseline was also predictive of reduced HR HPV clearance by log-rank test (over 48 weeks of follow-up). RESULTS: Baseline prevalence of HR-HPV was: anal 44% (N = 54/121); pharynx 3.8% (N = 5/131); semen 7.1% (N = 7/98). Seminal EBV shedding was present in 28% of participants and was associated with more than double the prevalence of detectable anal HR-HPV mRNA (71.4% for EBV shedders versus 33.3% for non-shedders, p < 0.01). In participants with detectable anal HR-HPV at baseline, we found increased persistence of HR-HPV over 48 weeks of follow-up (measured as time to first negative HR-HPV test in the EBV shedding group (p < 0.01). CONCLUSIONS: Seminal EBV shedding was associated with an increased risk of having detectable anal HR-HPV in a cohort of HIV infected MSM on suppressive ART. Future studies should examine if co-infection with EBV and HR-HPV may act synergistically in pathogenesis of anal cancer in HIV infected individuals. PMID- 26809561 TI - Protocol for a cluster-randomised trial to determine the effects of advocacy actions on the salt content of processed foods. AB - BACKGROUND: Corporate decisions affecting the composition of processed foods are a potent factor shaping the nutritional quality of the food supply. The addition of large quantities of salt to foods is incompatible with Australian Dietary Guidelines and the reformulation of processed foods to have less salt is a focus of non-governmental organisations (NGOs). There is evidence that advocacy can influence corporate behaviour but there are few data to define the effects of NGOs working in the food space. The aim of this study is to quantify the effects of advocacy delivered by a local NGO on the salt content of food products produced or marketed by companies in Australia. METHODS/DESIGN: This is a cluster randomised controlled trial that will be done in Australia from 2013 to 2015 which includes 45 food companies. The 23 companies in the control group will receive no specific intervention whilst the 22 companies in the intervention group will receive an advocacy program based upon an established theory of change model. The primary outcome will be the mean change in sodium content (mg/100 g) of processed foods produced or marketed by intervention compared to control companies assessed at 24 months. Interim outcomes (statements of support, published nutrition policies, level of engagement, knowledge and use of technology to reduce salt, salt reduction plans, and support for national initiatives) will also be assessed and a qualitative evaluation will provide more detailed insight. DISCUSSION: This novel study will provide robust randomised evidence about the effects of advocacy on food company behaviour and the quality of the processed food supply. A finding of improved food company behaviour will highlight the potential for greater investment in advocacy whilst the opposite result will reinforce the importance of government-led initiatives for the improvement of the food supply. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02373423. 26/02/2015. PMID- 26809562 TI - Accelerating Adverse Outcome Pathway Development Using Publicly Available Data Sources. AB - The adverse outcome pathway (AOP) concept links molecular perturbations with organism and population-level outcomes to support high-throughput toxicity (HTT) testing. International efforts are underway to define AOPs and store the information supporting these AOPs in a central knowledge base; however, this process is currently labor-intensive and time-consuming. Publicly available data sources provide a wealth of information that could be used to define computationally predicted AOPs (cpAOPs), which could serve as a basis for creating expert-derived AOPs in a much more efficient way. Computational tools for mining large datasets provide the means for extracting and organizing the information captured in these public data sources. Using cpAOPs as a starting point for expert-derived AOPs should accelerate AOP development. Coupling this with tools to coordinate and facilitate the expert development efforts will increase the number and quality of AOPs produced, which should play a key role in advancing the adoption of HTT testing, thereby reducing the use of animals in toxicity testing and greatly increasing the number of chemicals that can be tested. PMID- 26809563 TI - Analytical Complexity in Detection of Gene Variant-by-Environment Exposure Interactions in High-Throughput Genomic and Exposomic Research. AB - It seems intuitive that disease risk is influenced by the interaction between inherited genetic variants and environmental exposure factors; however, we have few documented interactions between variants and exposures. Advances in technology may enable the simultaneous measurement (i.e., on the same individuals in an epidemiological study) of millions of genome variants with thousands of environmental "exposome" factors, significantly increasing the number of possible factor pairs available for testing for the presence of interactions. The burden of analytic complexity, or sheer number of genetic and exposure factors measured, poses a considerable challenge for discovery of interactions in population-scale data. Advances in analytic approaches, large sample sizes, less conservative methods to mitigate multiple testing, and strong biological priors will be required to prune the search space to find reproducible and robust gene-by environment interactions in observational data. PMID- 26809564 TI - [Special aspects of analgosedation in cardiogenic shock patients]. AB - Patients with cardiogenic shock pose a challenge to physicians due to cardiorespiratory instability in addition to the underlying medical condition. If analgosedation and ventilation are indicated, commonly administered drugs themselves often influence hemodynamics and oxygenation. The present article provides an overview of the available substances with consideration of the patients' condition, then monitoring and optimization of analgosedation. PMID- 26809565 TI - Keeping up with the neighbor: a novel mechanism of call synchrony in Neoconocephalus ensiger katydids. AB - During solo calling, pulse periods gradually changed by up to 15% over several minutes. Pairs of calling males synchronized their pulses. The pulse rate (10-14 Hz) was considerably faster than the rate of synchronized signal units in other insects (0.5-3 Hz). Within each pulse cycle, males made only small adjustments to their pulse period, leading to regular switches of leader and follower roles. Large-scale timing adjustments only occurred in response to large delays. Stimulation with single pulses had no predictable effect on the timing of the male's next pulse, resulting in a flat phase response curve. When entrained to a stimulus with a faster pulse period, males briefly interrupted calling; they resumed calling largely synchronized with the stimulus. Throughout the stimulus, males made gradual changes to their pulse period, similar to those during pair calling. After the stimulus ended, pulse periods increased over several minutes, but did not return to their pre-stimulus values. Thus social context and intrinsic state of the males influenced pulse period in Neoconocephalus ensiger. These results indicate that N. ensiger males synchronize calls by adjusting their intrinsic pulse period, instead of adjusting the timing of individual pulses, as described in other synchronizing insects. PMID- 26809567 TI - Genetic Control Of Malaria Mosquitoes. AB - Experiments demonstrating the feasibility of genetically modifying mosquito vectors to impair their ability to transmit the malaria parasite have been known for well over a decade. However, means to spread resistance or population control genes into wild mosquito populations remains an unsolved challenge. Two recent reports give hope that CRISPR technology may allow such challenge to be overcome. PMID- 26809568 TI - The impact of capacity growth in national telecommunications networks. AB - This paper discusses both UK-based and global Internet data bandwidth growth, beginning with historical data for the BT network. We examine the time variations in consumer behaviour and how this is statistically aggregated into larger traffic loads on national core fibre communications networks. The random nature of consumer Internet behaviour, where very few consumers require maximum bandwidth simultaneously, provides the opportunity for a significant statistical gain. The paper looks at predictions for how this growth might continue over the next 10-20 years, giving estimates for the amount of bandwidth that networks should support in the future. The paper then explains how national networks are designed to accommodate these traffic levels, and the various network roles, including access, metro and core, are described. The physical layer network is put into the context of how the packet and service layers are designed and the applications and location of content are also included in an overall network overview. The specific role of content servers in alleviating core network traffic loads is highlighted. The status of the relevant transmission technologies in the access, metro and core is given, showing that these technologies, with adequate research, should be sufficient to provide bandwidth for consumers in the next 10-20 years. PMID- 26809569 TI - New optical fibres for high-capacity optical communications. AB - Researchers are within a factor of 2 or so from realizing the maximum practical transmission capacity of conventional single-mode fibre transmission technology. It is therefore timely to consider new technological approaches offering the potential for more cost-effective scaling of network capacity than simply installing more and more conventional single-mode systems in parallel. In this paper, I review physical layer options that can be considered to address this requirement including the potential for reduction in both fibre loss and nonlinearity for single-mode fibres, the development of ultra-broadband fibre amplifiers and finally the use of space division multiplexing. PMID- 26809570 TI - The benefits of convergence. AB - A multi-tier radio access network (RAN) combining the strength of fibre-optic and radio access technologies employing adaptive microwave photonics interfaces and radio-over-fibre (RoF) techniques is envisioned for future heterogeneous wireless communications. All-band radio spectrum from 0.1 to 100 GHz will be used to deliver wireless services with high capacity, high link speed and low latency. The multi-tier RAN will improve the cell-edge performance in an integrated heterogeneous environment enabled by fibre-wireless integration and networking for mobile fronthaul/backhaul, resource sharing and all-layer centralization of multiple standards with different frequency bands and modulation formats. In essence, this is a 'no-more-cells' architecture in which carrier aggregation among multiple frequency bands can be easily achieved with seamless handover between cells. In this way, current and future mobile network standards such as 4G and 5G can coexist with optimized and continuous cell coverage using multi tier RoF regardless of the underlying network topology or protocol. In terms of users' experience, the future-proof approach achieves the goals of system capacity, link speed, latency and continuous heterogeneous cell coverage while overcoming the bandwidth crunch in next-generation communication networks. PMID- 26809571 TI - Optical network democratization. AB - The current Internet infrastructure is not able to support independent evolution and innovation at physical and network layer functionalities, protocols and services, while at same time supporting the increasing bandwidth demands of evolving and heterogeneous applications. This paper addresses this problem by proposing a completely democratized optical network infrastructure. It introduces the novel concepts of the optical white box and bare metal optical switch as key technology enablers for democratizing optical networks. These are programmable optical switches whose hardware is loosely connected internally and is completely separated from their control software. To alleviate their complexity, a multi dimensional abstraction mechanism using software-defined network technology is proposed. It creates a universal model of the proposed switches without exposing their technological details. It also enables a conventional network programmer to develop network applications for control of the optical network without specific technical knowledge of the physical layer. Furthermore, a novel optical network virtualization mechanism is proposed, enabling the composition and operation of multiple coexisting and application-specific virtual optical networks sharing the same physical infrastructure. Finally, the optical white box and the abstraction mechanism are experimentally evaluated, while the virtualization mechanism is evaluated with simulation. PMID- 26809572 TI - Maximizing the optical network capacity. AB - Most of the digital data transmitted are carried by optical fibres, forming the great part of the national and international communication infrastructure. The information-carrying capacity of these networks has increased vastly over the past decades through the introduction of wavelength division multiplexing, advanced modulation formats, digital signal processing and improved optical fibre and amplifier technology. These developments sparked the communication revolution and the growth of the Internet, and have created an illusion of infinite capacity being available. But as the volume of data continues to increase, is there a limit to the capacity of an optical fibre communication channel? The optical fibre channel is nonlinear, and the intensity-dependent Kerr nonlinearity limit has been suggested as a fundamental limit to optical fibre capacity. Current research is focused on whether this is the case, and on linear and nonlinear techniques, both optical and electronic, to understand, unlock and maximize the capacity of optical communications in the nonlinear regime. This paper describes some of them and discusses future prospects for success in the quest for capacity. PMID- 26809573 TI - From photons to big-data applications: terminating terabits. AB - Computer architectures have entered a watershed as the quantity of network data generated by user applications exceeds the data-processing capacity of any individual computer end-system. It will become impossible to scale existing computer systems while a gap grows between the quantity of networked data and the capacity for per system data processing. Despite this, the growth in demand in both task variety and task complexity continues unabated. Networked computer systems provide a fertile environment in which new applications develop. As networked computer systems become akin to infrastructure, any limitation upon the growth in capacity and capabilities becomes an important constraint of concern to all computer users. Considering a networked computer system capable of processing terabits per second, as a benchmark for scalability, we critique the state of the art in commodity computing, and propose a wholesale reconsideration in the design of computer architectures and their attendant ecosystem. Our proposal seeks to reduce costs, save power and increase performance in a multi-scale approach that has potential application from nanoscale to data-centre-scale computers. PMID- 26809574 TI - Cooperation and information replication in wireless networks. AB - A significant portion of today's network traffic is due to recurring downloads of a few popular contents. It has been observed that replicating the latter in caches installed at network edges-close to users-can drastically reduce network bandwidth usage and improve content access delay. Such caching architectures are gaining increasing interest in recent years as a way of dealing with the explosive traffic growth, fuelled further by the downward slope in storage space price. In this work, we provide an overview of caching with a particular emphasis on emerging network architectures that enable caching at the radio access network. In this context, novel challenges arise due to the broadcast nature of the wireless medium, which allows simultaneously serving multiple users tuned into a multicast stream, and the mobility of the users who may be frequently handed off from one cell tower to another. Existing results indicate that caching at the wireless edge has a great potential in removing bottlenecks on the wired backbone networks. Taking into consideration the schedule of multicast service and mobility profiles is crucial to extract maximum benefit in network performance. PMID- 26809575 TI - Communication networks beyond the capacity crunch. AB - This issue of Philosophical Transactions of the Royal Society, Part A represents a summary of the recent discussion meeting 'Communication networks beyond the capacity crunch'. The purpose of the meeting was to establish the nature of the capacity crunch, estimate the time scales associated with it and to begin to find solutions to enable continued growth in a post-crunch era. The meeting confirmed that, in addition to a capacity shortage within a single optical fibre, many other 'crunches' are foreseen in the field of communications, both societal and technical. Technical crunches identified included the nonlinear Shannon limit, wireless spectrum, distribution of 5G signals (front haul and back haul), while societal influences included net neutrality, creative content generation and distribution and latency, and finally energy and cost. The meeting concluded with the observation that these many crunches are genuine and may influence our future use of technology, but encouragingly noted that research and business practice are already moving to alleviate many of the negative consequences. PMID- 26809576 TI - Social value of high bandwidth networks: creative performance and education. AB - This paper considers limitations of existing network technologies for distributed theatrical performance in the creative arts and for symmetrical real-time interaction in online learning environments. It examines the experience of a multidisciplinary research consortium that aimed to introduce a solution to latency and other network problems experienced by users in these sectors. The solution builds on the Multicast protocol, Access Grid, an environment supported by very high bandwidth networks. The solution is intended to offer high-quality image and sound, interaction with other network platforms, maximum user control of multipoint transmissions, and open programming tools that are flexible and modifiable for specific uses. A case study is presented drawing upon an extended period of participant observation by the authors. This provides a basis for an examination of the challenges of promoting technological innovation in a multidisciplinary project. We highlight the kinds of technical advances and cultural and organizational changes that would be required to meet demanding quality standards, the way a research consortium planned to engage in experimentation and learning, and factors making it difficult to achieve an open platform that is responsive to the needs of users in the creative arts and education sectors. PMID- 26809577 TI - 5G: rethink mobile communications for 2020+. AB - The 5G network is anticipated to meet the challenging requirements of mobile traffic in the 2020s, which are characterized by super high data rate, low latency, high mobility, high energy efficiency and high traffic density. This paper provides an overview of China Mobile's 5G vision and potential solutions. Three key characteristics of 5G are analysed, i.e. super fast, soft and green. The main 5G R&D themes are further elaborated, which include five fundamental rethinkings of the traditional design methodologies. The 5G network design considerations are also discussed, with cloud radio access network, ultra-dense network, software defined network and network function virtualization examined as key potential solutions towards a green and soft 5G network. The paradigm shift to user-centric network operation from the traditional cell-centric operation is also investigated, where the decoupled downlink and uplink, control and data, and adaptive multiple connections provide sufficient means to achieve a user-centric 5G network with 'no more cells'. The software defined air interface is investigated under a uniform framework and can adaptively adapt the parameters to well satisfy various requirements in different 5G scenarios. PMID- 26809578 TI - Implications of information theory in optical fibre communications. AB - Recent decades have witnessed steady improvements in our ability to harness the information-carrying capability of optical fibres. Will this process continue, or will progress eventually stall? Information theory predicts that all channels have a limited capacity depending on the available transmission resources, and thus it is inevitable that the pace of improvements will slow. However, information theory also provides insights into how transmission resources should, in principle, best be exploited, and thus may serve as a guide for where to look for better ways to squeeze more out of a precious resource. This tutorial paper reviews the basic concepts of information theory and their application in fibre optic communications. PMID- 26809579 TI - Future traffic demands and characteristics from a media perspective. AB - Providing topical information and entertainment began with wall paintings, the spoken word and face-to-face performance, then the addition of the written and printed word along with illustrations and pictures, followed by audio recording. In the early 1920s, regular broadcast radio services began, followed by television in the late 1930s, and this has provided the basis of broadcast media we know today. These innovations frequently pushed boundaries and challenged the status quo, but not all of these challenges were technical by any means. However, it could be argued that the development of accessible technologies has been fundamental to the successful deployment of information and entertainment media in all their forms throughout history. Today, the merging of audio and video media with a whole range of digital services is becoming commonplace. With the ability of such services to develop new approaches in supporting people's everyday living experiences, this will take communication networks into a new era central to the way we live. This paper postulates that the historical trends with audio and video media developments from the early 1900s will continue to push future boundaries, and attempts to highlight the key demands and the developing trends from a communication network point of view. PMID- 26809580 TI - Once the Internet can measure itself. AB - In communications, the obstacle to high bandwidth and reliable transmission is usually the interconnections, not the links. Nowhere is this more evident than on the Internet, where broadband connections to homes, offices and now mobile smart phones are a frequent source of frustration, and the interconnections between the roughly 50,000 subnetworks (autonomous systems or ASes) from which it is formed, even more so. The structure of the AS graph that is formed by these interconnections is unspecified, undocumented and only guessed-at through measurement, but it shows surprising efficiencies. Under recent pressures for network neutrality and openness or 'transparency', operators, several classes of users and regulatory bodies have a good chance of realizing these efficiencies, but they need improved measurement technology to manage this under continued growth. A long-standing vision, an Internet that measures itself, in which every intelligent port takes a part in monitoring, can make this possible and may now be within reach. PMID- 26809581 TI - Energy challenges in optical access and aggregation networks. AB - Scalability is a critical issue for access and aggregation networks as they must support the growth in both the size of data capacity demands and the multiplicity of access points. The number of connected devices, the Internet of Things, is growing to the tens of billions. Prevailing communication paradigms are reaching physical limitations that make continued growth problematic. Challenges are emerging in electronic and optical systems and energy increasingly plays a central role. With the spectral efficiency of optical systems approaching the Shannon limit, increasing parallelism is required to support higher capacities. For electronic systems, as the density and speed increases, the total system energy, thermal density and energy per bit are moving into regimes that become impractical to support-for example requiring single-chip processor powers above the 100 W limit common today. We examine communication network scaling and energy use from the Internet core down to the computer processor core and consider implications for optical networks. Optical switching in data centres is identified as a potential model from which scalable access and aggregation networks for the future Internet, with the application of integrated photonic devices and intelligent hybrid networking, will emerge. PMID- 26809582 TI - Ghrelin and Neurodegenerative Disorders-a Review. AB - Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor 1a (GHS-R1a), is a gut-derived, orexigenic peptide hormone that primarily regulates growth hormone secretion, food intake, and energy homeostasis. With the wide expression of GHS-R1a in extra-hypothalamic regions, the physiological role of ghrelin is more extensive than solely its involvement in metabolic function. Ghrelin has been shown to be involved in numerous higher brain functions, such as memory, reward, mood, and sleep. Some of these functions are disrupted in neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). This link between ghrelin and these neurodegenerative diseases is supported by numerous studies. This review aims to provide a comprehensive overview of the most recent evidence of the novel neuromodulatory role of ghrelin in PD, AD, and HD. Moreover, the changes in circulating and/or central ghrelin levels that are associated with disease progression are also postulated to be a biomarker for clinical diagnosis and therapy. PMID- 26809583 TI - Bergmann Glia, Long-Term Depression, and Autism Spectrum Disorder. AB - Bergmann glia (BG), a specific type of radial astrocytes in the cerebellum, play a variety of vital functions in the development of this structure. However, the possible role of BG in the development of abnormalities observed in individuals with autism spectrum disorder (ASD) seems to be underestimated. One of the most consistent findings observed in ASD patients is loss of Purkinje cells (PCs). Such a defect may be caused by dysregulation of glutamate homeostasis, which is maintained mainly by BG. Moreover, these glial cells are involved in long-term depression (LTD), a form of plasticity which can additionally subserve neuroprotective functions. The aim of presented review is to summarize the current knowledge about interactions which occur between PC and BG, with special emphasis on those which are relevant to the survival and proper functioning of cerebellar neurons. PMID- 26809585 TI - Posttraumatic Stress and Prolonged Grief After the Sudden Cardiac Death of a Young Relative. PMID- 26809584 TI - Metabolic Syndrome After Roux-en-Y Gastric Bypass Surgery in Chinese Obese Patients with Type 2 Diabetes. AB - BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery is currently the most effective treatment for substantial and sustained weight loss in morbidly obese individuals. We aim to determine the prevalence in Chinese obese patients with type 2 diabetes (T2DM) and the efficacy of surgical treatment of the metabolic syndrome (MetS) and its components with a control group in medical therapy. METHODS: A total of 121 obese T2DM individuals who underwent RYGB and 93 nonoperative obese patients with T2DM were enrolled in the study. MetS was defined according to the criteria established by the Chinese Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults (JCDCG). We determined the change in MetS and the prevalence of its components and performed logistic regression models to evaluate predictors of MetS remission. RESULTS: One year after RYGB, all MetS components improved in the RYGB group and medication use decreased. Of the RYGB group, MetS prevalence decreased from 108 patients (83.3 %) to 20 (16.5 %), and from 88 patients (94.6 %) to 76 (81.7 %) in the control group. Multiple logistic regression analyses indicated that a shorter diabetes duration and higher percent excess weight loss (%EWL) were associated with a greater chance of MetS remission after surgery. CONCLUSIONS: RYGB induces considerable and persistent improvement in MetS prevalence in Chinese obese patients with T2DM. Diabetes duration and %EWL might act as potential prognostic markers in predicting the MetS reversibility. PMID- 26809586 TI - Linking Adverse Childhood Effects and Attachment: A Theory of Etiology for Sexual Offending. AB - Sexual violence continues to be a significant public health problem affecting significant portions of the population. Unfortunately, an agreed upon theory of etiology remains elusive leading to challenges in developing effective prevention and treatment interventions. Recently, there is a growing body of literature examining the role of adverse childhood experiences (ACEs) in the development of sexually violent behavior. This research has begun to explore the rates of various types of child maltreatments and family dysfunction in individuals who have been convicted of a sexual crime. These empirical inquiries have been primarily descriptive in nature and have not yet provided a cohesive theoretical model as to why the presence of ACEs might contribute to sexually abusive behavior. This article suggests that attachment theory offers an explanatory link between early adversity and sexually abusive behavior in adulthood. We first summarize important attachment theory concepts, then integrate them with research in the area of developmental psychopathology and ACEs, and finally propose a model by which attachment can be used as an explanatory theory for subsequent sexualized coping and sexually abusive behaviors. Finally, this article explores the implications for practice, policy, and research using this explanatory theory as a framework for understanding sexual violence. PMID- 26809588 TI - Telemental Health: Digital Disruption and the Opportunity to Expand Care. AB - Telemental health, which involves clinicians connecting remotely to patients via teleconferencing, has seen growing interest. In addition to providing in-home treatment, this technology allows specialists to provide care in remote and underserved areas. Current research suggests that both patients and clinicians are satisfied with telemental health services and that it is comparable in terms of quality to in-person care. Nonetheless, concerns still exist regarding its effects on the role of clinicians and the care they provide. PMID- 26809587 TI - The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium. AB - Epithelial morphogenesis and stability are essential for normal development and organ homeostasis. The mouse neural plate is a cuboidal epithelium that remodels into a columnar pseudostratified epithelium over the course of 24 hr. Here we show that the transition to a columnar epithelium fails in mutant embryos that lack the tumor suppressor PTEN, although proliferation, patterning and apical basal polarity markers are normal in the mutants. The Pten phenotype is mimicked by constitutive activation of PI3 kinase and is rescued by the removal of PDK1 (PDPK1), but does not depend on the downstream kinases AKT and mTORC1. High resolution imaging shows that PTEN is required for stabilization of planar cell packing in the neural plate and for the formation of stable apical-basal microtubule arrays. The data suggest that appropriate levels of membrane associated PDPK1 are required for stabilization of apical junctions, which promotes cell elongation, during epithelial morphogenesis. PMID- 26809589 TI - Regulation of ZAT12 protein stability: The role of hydrogen peroxide. AB - Signaling mediated by reactive oxygen species (ROS) has emerged as a key component of plants' responses to environmental stress. The ROS-regulated transcription factor ZAT12 was revealed as a negative regulator of iron (Fe) deficiency responses through its direct interaction with the bHLH protein FIT. In the epidermis of the early root differentiation zone, ZAT12 stability depended on the presence of the ZAT12 EAR motif. It was concluded that ZAT12 may be the target of 2 alternative degradation pathways. Here, we present a model aiming to explain the regulatory mechanisms by which ZAT12 could be targeted for degradation and to predict the types of potential regulators involved. In addition to an E3 ubiquitin ligase, we predict 2 critical regulatory factors, namely a protein interacting with the ZAT12 EAR motif and a ROS-responsive regulatory protein. PMID- 26809590 TI - Swelling of Poly(n-butyl methacrylate) Films Exposed to Supercritical Carbon Dioxide: A Comparative Study with Polystyrene. AB - We report here the swelling and relaxation properties of confined poly(n-butyl methacrylate) (PBMA) films having thicknesses of less than 70 nm under supercritical carbon dioxide (scCO2) using the X-ray reflectivity technique. Swellability is found to be dominant in thinner films compared to thicker ones as a consequence of the confinement-induced densification of the former. Swellability is proportionately increased with the density of the film. PBMA films exhibit a more significant swelling than do PS films, and their differences become more prominent with the increase in film thickness. A comparison between the results obtained for polystyrene (PS) and PBMA ultrathin films reveals that the swellability is dependent upon the specific intermolecular interaction between CO2 and the chemical groups available in the polymers. Owing to strong Lewis acid-base interactions with scCO2 and the lower glass-transition temperature (bulk Tg ~ 29 degrees C), PBMA films exhibit a greater amount of swelling than do PS films (bulk Tg ~ 100 degrees C). Though they reach to the different swollen state upon exposition, identical relaxation behavior as a function of aging time is evidenced. This unprecedented behavior can be ascribed to the strong bonding between trapped CO2 and PBMA that probably impedes the release of CO2 molecules from the swollen PBMA films manifested in suppressed relaxation. PMID- 26809591 TI - Decreased antimicrobial resistance and defined daily doses after implementation of a clinical culture-guided antimicrobial stewardship program in a local hospital. AB - BACKGROUND: We aimed to report the implementation of an antimicrobial stewardship program (ASP) guided by clinically significant cultures in a hospital to assess its pharmaceutical, microbiological, financial, and outcome effects. METHODS: A 3 year cohort study of an antimicrobial restriction policy implementation was performed. The ASP with culture-guided de-escalation of antibiotics was instituted in a local hospital since January 1, 2012. The cost of antimicrobials, defined daily dose (DDD), susceptibility to antimicrobials, and outcome of all admitted patients were calculated and evaluated before and after the ASP implementation. RESULTS: Average monthly length of stay of admitted patients decreased from 7.8 +/- 0.5 days in 2011 to 6.9 +/- 0.3 days in 2013 (p < 0.001). The average monthly cost of antimicrobials decreased 46.9% from US$30,146.8 in 2011 to US$16,021.3 in 2013 (p < 0.001). Total intravenous antimicrobial DDDs per 100 bed-days of the inpatients were 66.9, 54.1 and 48.4 in 2011, 2012 and 2013, respectively. A total of 18.6 DDDs per 100 bed-days of inpatients (27.7%) decreased from 2011 to 2013. By comparing data in 2013 to those in 2011, the ASP reduced antimicrobial resistance of Gram-positive bacteria (p = 0.013), Gram negative bacteria (p < 0.001), and predominant species (all p < 0.05). The yearly mortality also decreased from 1.3% in 2011 to 1.1% in 2012 and 1.0% in 2013. CONCLUSIONS: The ASP with a culture-guided de-escalation of antibiotics successfully reduced length of stay, mortality, the cost of antimicrobials, DDDs, and antimicrobial resistance rate, and that is highly recommended for local hospitals. PMID- 26809592 TI - Peer beliefs and smoking in adolescence: a longitudinal social network analysis. AB - BACKGROUND: Peer smoking is one of the strongest predictors of adolescent cigarette use, but less is known about whether other peer characteristics also contribute to this behavior. OBJECTIVES: This study examined the links between adolescent cigarette use and peer beliefs about smoking. It tested whether peer beliefs about smoking are associated with changes in cigarette use, whether this association is a result of changes in individual beliefs about smoking, and how beliefs inform friendship choices. METHODS: Analyses drew on data collected from 29 school-based networks, each measured at five occasions as students moved from 6th through 9th grade, as part of the study of the PROSPER partnership model. Longitudinal social network models provided estimates of friendship selection and behavior for an average of 6,200 students at each measurement point and more than 9,000 students overall. RESULTS: Peer beliefs about smoking influenced cigarette use both directly and through their impact on individual beliefs. Respondents tended to name friends whose beliefs about smoking were similar to their own, and the likelihood of being named as a friend was higher for those who reported more positive beliefs about smoking. CONCLUSION: The results from this study suggest that peer beliefs about smoking, in addition to peer cigarette use itself, are associated with adolescent smoking through several mechanisms. Because beliefs favorable to cigarette use are present before adolescents actually smoke, these results underscore the importance of implementing smoking prevention programs in early adolescence. PMID- 26809594 TI - Maxillary "All-On-Four" treatment using zygomatic implants. A mechanical analysis. AB - OBJECTIVE: Zygomatic implants may be used for dental rehabilitation in atrophic maxillae. The aim of this study was to establish experimentally the areas of stress distribution using 2 kinds of "All-On-Four" maxillary procedures. STUDY DESIGN: The best position to insert the implants was selected using polyurethane craniomaxillary models and surgical guides were made. Group 1 was designed with two posterior zygomatic implants and two conventional anterior implants, and group 2 with two posterior zygomatic implants and two anterior zygomatic implants. A titanium bar was built to link the 4 implants in both groups. Photoelastic replicas of these models were made and the implants were inserted using the surgical guides. An Instrom 4411 testing machine was used to perform a unilateral compressive loading at the level of the right first molar until 2mm of displacement was obtained. RESULTS: Group 1 showed a high strain concentration in the right lateral orbital region at the level of the apex of the zygomatic implant. Less strain was noticed at the apical levels of the conventional implants in the anterior sector and of the contralateral zygomatic implant. Group 2 showed high strains in the lateral inferior orbital area. The load was low in the alveolar bone sector. DISCUSSION: Zygomatic bone and paranasal structures are loaded at high levels when zygomatic implants are used to stabilize a full maxillary prosthodontic rehabilitation on 4 implants. The use of 4 zygomatic implants loads the alveolar bone to a lower extent and seems better suited from a mechanical point of view than the use of 2 zygomatic implants. PMID- 26809595 TI - [Comment about the article: " Vigneron A, Morand B, Lafontaine V, Lesne V, Bettega G. Maxillary advancement osteotomy with sequelae cleft lip and palate: Dilemna between occlusion and aesthetic profile. Rev Stomatol Chir Maxillofac Chir Orale 2015;116:289-95 "]. PMID- 26809596 TI - [Congenital dacryocystocele: Surgical treatment or routine follow-up?]. AB - INTRODUCTION: Congenital dacryocystoceles are rare and often misunderstood pathologies. Their treatment varies and consists in simple follow-up, lacrimal catheterization or endoscopic surgical drainage, depending on medical teams. The aim of our study was to discuss the place of endoscopic drainage in the treatment of congenital dacryocystocele. METHODS: We conducted a retrospective review on 18 cases of congenital dacryocystoceles taken in charge in a tertiary care center between 2009 and 2012. RESULTS: Thirteen newborns, including five bilateral cases, were taken in charge. The average age was 14.6 days. Six newborns presented with an acute dacryocystitis at the time of diagnosis. No respiratory complications were observed. Spontaneous drainage of the dacryocystocele was observed in 38.8% of the cases, occurring at 22 days of life on average. Endonasal endoscopic drainage was performed in 66.6% of the cases. No recurrence or complication was observed after surgery. After spontaneous drainage, one recurrence was observed. The mean follow-up period of these patients was 8.8 months. DISCUSSION: Spontaneous drainage is common. Conservative management may therefore be considered in absence of infection. In case of infection and/or persistence of dacryocystocele after 4 weeks of life, endonasal surgical drainage should be considered. Imaging of the facial structure should be performed before any surgical treatment. PMID- 26809598 TI - [Plunging ranula. Review]. AB - INTRODUCTION: Ranula is a pseudocyst of the sublingual gland, often of unknown etiology. In few cases, it can extend to the neck when passing through the mylohyoid muscle. Diagnosis is not always easy as other cervical cystic lesions may have the same clinical aspect. Some ranulas recur after removal. The aim of our study was to conduct a review about plunging ranulas, with a focus on the most useful paraclinical exams and the most effective treatment. MATERIAL AND METHODS: A review of the literature has been conducted in the PubMed database between 2015 and 2010 using following keywords: plunging ranula, recurrent plunging ranula. RESULTS: Thirteen articles reporting 37 cases of plunging ranulas have been selected. Among these cases, 3 recurred. Paraclinical exams consisted in US, CT scan and MRI. Main reported treatment was sublingual gland removal, sometime associated with marsupialization. DISCUSSION: The most useful paraclinical exam is CT scan. Total sublingual gland removal is the most efficient treatment. PMID- 26809599 TI - [A sublingual tumefaction in an infant]. PMID- 26809601 TI - Challenges and Solutions for Depression Prevention Research: Methodology for a Depression Prevention Trial for Older Adults with Knee Arthritis and Emotional Distress. AB - OBJECTIVE: To describe the methodology, challenges, and baseline characteristics of a prevention development trial entitled "Reducing Pain, Preventing Depression." METHODS: A sequential multiple assignment randomized trial (SMART) compared sequences of cognitive behavioral therapy (CBT) and physical therapy for knee pain and prevention of depression and anxiety. Participants were randomized to CBT, physical therapy, or enhanced usual care and followed for 12 months for new-episode depression or anxiety. Participants were age >= 60 with knee osteoarthritis and subsyndromal depression, defined as 9-item Patient Health Questionnaire (PHQ-9) score >=1 (which included the endorsement of one of the cardinal symptoms of depression [low mood or anhedonia]) and no diagnosis of major depressive disorder per the Structured Clinical Interview for DSM-IV. Depression and anxiety severity and characterization of new episodes were assessed with the PHQ-9, Generalized Anxiety Disorder-7, and the PRIME-MD. Knee pain was characterized with the Western Ontario McMaster Arthritis Index. Response was defined as at least "Very Much Better" on a Patient Global Impression of Change. RESULTS: At baseline there were 99 patients with an average age of 71; 61.62% were women and 81.8% white. The average PHQ-9 was 5.6 and average Generalized Anxiety Disorder-7, was 3.2. Most were satisfied with the interventions and study procedures. The challenges and solutions described here will also be used in a confirmatory clinical trial of efficacy. CONCLUSION: A SMART design for depression and anxiety prevention, using both CBT and physical therapy, appears to be feasible and acceptable to participants. The methodologic innovations of this project may advance the field of late-life depression and anxiety prevention. PMID- 26809602 TI - Common Sense Model Factors Affecting African Americans' Willingness to Consult a Healthcare Provider Regarding Symptoms of Mild Cognitive Impairment. AB - OBJECTIVE: Although at increased risk for developing dementia compared with white patients, older African Americans are diagnosed later in the course of dementia. Using the common sense model (CSM) of illness perception, we sought to clarify processes promoting timely diagnosis of mild cognitive impairment (MCI) for African American patients. DESIGN, SETTING, PARTICIPANTS: In-person, cross sectional survey data were obtained from 187 African American (mean age: 60.44 years). Data were collected at social and health-focused community events in three southern Wisconsin cities. MEASUREMENTS: The survey represented a compilation of published surveys querying CSM constructs focused on early detection of memory disorders, and willingness to discuss concerns about memory loss with healthcare providers. Derived CSM variables measuring perceived causes, consequences, and controllability of MCI were included in a structural equation model predicting the primary outcome: Willingness to discuss symptoms of MCI with a provider. RESULTS: Two CSM factors influenced willingness to discuss symptoms of MCI with providers: Anticipation of beneficial consequences and perception of low harm associated with an MCI diagnosis predicted participants' willingness to discuss concerns about cognitive changes. No association was found between perceived controllability and causes of MCI, and willingness to discuss symptoms with providers. CONCLUSIONS: These data suggest that allaying concerns about the deleterious effects of a diagnosis, and raising awareness of potential benefits, couldinfluence an African American patient's willingness to discuss symptoms of MCI with a provider. The findings offer guidance to designers of culturally congruent MCI education materials, and healthcare providers caring for older African Americans. . PMID- 26809603 TI - Executive Functioning in Participants Over Age of 50 with Hoarding Disorder. AB - OBJECTIVES: The current investigation utilized mid-life and late-life participants diagnosed with hoarding disorder (HD) to explore the relationship between executive functioning and hoarding severity. DESIGN: Correlational analyses were used to investigate the associations between executive functioning and hoarding severity in nondemented participants. Multiple regression was used to determine if executive functioning had a unique association with HD severity when accounting for depressive symptoms. SETTING: Participants were recruited from the San Diego area for HD intervention studies. PARTICIPANTS: Participants were 113 nondemented adults aged 50-86 years who met DSM-5 criteria for HD. The mean age of the sample utilized in the analyses was 63.76 years (SD, 7.2; range, 51-85 years). The sample was mostly female (72%), Caucasian (81.4%), and unmarried (78%). MEASUREMENTS: Hoarding severity was assessed using the Saving Inventory-Revised and the Clutter Image Rating and depression was assessed using the Hospital Anxiety and Depression Scale. Executive functioning was assessed using the Wisconsin Card Sorting Test (WCST-128) and the Trail Making and Verbal Fluency subtests of the Delis-Kaplan Executive Function System. RESULTS: Executive function (operationalized as perseveration on the WCST-128) was significantly associated with Clutter Image Ratings. In a multivariate context, executive function and depressive symptom severity were both significant predictors of variance in Clutter Image Rating. CONCLUSIONS: Our results suggest that executive function is related to severity of HD symptoms and should be considered as part of the conceptualization of HD. PMID- 26809604 TI - Opportunities for Nanoscience and Nanotechnology in Studying Microbiomes. PMID- 26809606 TI - Perspectives of rural carers on benefits and barriers of receiving occupational therapy via Information and Communication Technologies. AB - INTRODUCTION: People with a disability living in rural areas commonly experience difficulty in accessing therapy services. Information and Communication Technologies (ICT) may have the potential to provide occupational therapy services remotely through two-way visual interactions. The aim of this qualitative study was to understand the perspectives of carers of a person with a disability living in rural New South Wales (NSW) on the use of ICT for occupational therapy service delivery. METHODS: Individual semi-structured telephone interviews were conducted with 11 carers of persons with a disability living in rural NSW. Participants were asked about their use of technology, therapy experiences and their attitudes towards using ICT to receive occupational therapy for their son/daughter. Data were analysed via constant comparison and thematic analysis. RESULTS: Participants were willing to use ICT to enhance their current access to therapy based on their in-depth knowledge of their son or daughter and their prior experiences with therapy and technology. For ICT to work for occupational therapy, participants identified the need for support and access prior to, during and between ICT sessions. CONCLUSION: From the carers' perspectives, ICT has the potential to increase access to occupational therapy services for people with a disability who live in rural NSW. Occupational therapists could benefit from eliciting the experiences, knowledge and willingness of rural carers to deliver therapy via ICT, thereby supplementing and enhancing in-person service delivery. PMID- 26809607 TI - Effect of Variation in Test Methods on Performance of Ultraviolet-C Radiation Room Decontamination. AB - OBJECTIVE: To determine the effect of variation in test methods on performance of an ultraviolet-C (UV-C) room decontamination device. DESIGN: Laboratory evaluation. METHODS: We compared the efficacy of 2 UV-C room decontamination devices with low pressure mercury gas bulbs. For 1 of the devices, we evaluated the effect of variation in spreading of the inoculum, carrier orientation relative to the device, type of organic load, type of carrier, height of carrier, and uninterrupted versus interrupted exposures on measured UV-C killing of methicillin-resistant Staphylococcus aureus and Clostridium difficile spores. RESULTS: The 2 UV-C room decontamination devices achieved similar log10 colony forming unit reductions in the pathogens with exposure times ranging from 5 to 40 minutes. On steel carriers, spreading of the inoculum over a larger surface area significantly enhanced killing of both pathogens, such that a 10-minute exposure on a 22-mm2 disk resulted in greater than 2 log reduction in C. difficile spores. Orientation of carriers in parallel rather than perpendicular with the UV-C lamps significantly enhanced killing of both pathogens. Different types of organic load also significantly affected measured organism reductions, whereas type of carrier, variation in carrier height, and interrupted exposure cycles did not. CONCLUSIONS: Variation in test methods can significantly impact measured reductions in pathogens by UV-C devices during experimental testing. Our findings highlight the need for standardized laboratory methods for testing the efficacy of UV-C devices and for evaluations of the efficacy of short UV-C exposure times in real-world settings. PMID- 26809609 TI - Frequent chloroplast RNA editing in early-branching flowering plants: pilot studies on angiosperm-wide coexistence of editing sites and their nuclear specificity factors. AB - BACKGROUND: RNA editing by cytidine-to-uridine conversions is an essential step of RNA maturation in plant organelles. Some 30-50 sites of C-to-U RNA editing exist in chloroplasts of flowering plant models like Arabidopsis, rice or tobacco. We now predicted significantly more RNA editing in chloroplasts of early branching angiosperm genera like Amborella, Calycanthus, Ceratophyllum, Chloranthus, Illicium, Liriodendron, Magnolia, Nuphar and Zingiber. Nuclear encoded RNA-binding pentatricopeptide repeat (PPR) proteins are key editing factors expected to coevolve with their cognate RNA editing sites in the organelles. RESULTS: With an extensive chloroplast transcriptome study we identified 138 sites of RNA editing in Amborella trichopoda, approximately the 3- to 4-fold of cp editing in Arabidopsis thaliana or Oryza sativa. Selected cDNA studies in the other early-branching flowering plant taxa furthermore reveal a high diversity of early angiosperm RNA editomes. Many of the now identified editing sites in Amborella have orthologues in ferns, lycophytes or hornworts. We investigated the evolution of CRR28 and RARE1, two known Arabidopsis RNA editing factors responsible for cp editing events ndhBeU467PL, ndhDeU878SL and accDeU794SL, respectively, all of which we now found conserved in Amborella. In a phylogenetically wide sampling of 65 angiosperm genomes we find evidence for only one single loss of CRR28 in chickpea but several independent losses of RARE1, perfectly congruent with the presence of their cognate editing sites in the respective cpDNAs. CONCLUSION: Chloroplast RNA editing is much more abundant in early-branching than in widely investigated model flowering plants. RNA editing specificity factors can be traced back for more than 120 million years of angiosperm evolution and show highly divergent patterns of evolutionary losses, matching the presence of their target editing events. PMID- 26809612 TI - One in seven colorectal cancer patients is under 50, US study shows. PMID- 26809611 TI - Follow-up of atheroma burden with sequential whole body contrast enhanced MR angiography: a feasibility study. AB - Assess the feasibility of whole body magnetic resonance angiography (WB-MRA) for monitoring global atheroma burden in a population with peripheral arterial disease (PAD). 50 consecutive patients with symptomatic PAD referred for clinically indicated MRA were recruited. Whole body MRA (WB-MRA) was performed at baseline, 6 months and 3 years. The vasculature was split into 31 anatomical arterial segments. Each segment was scored according to degree of luminal narrowing: 0 = normal, 1 = <50 %, 2 = 50-70 %, 3 = 71-99 %, 4 = vessel occlusion. The score from all assessable segments was summed, and then normalised to the number of assessable vessels. This normalised score was divided by four (the maximum vessel score) and multiplied by 100 to give a final standardised atheroma score (SAS) with a score of 0-100. Progression was assessed with repeat measure ANOVA. 36 patients were scanned at 0 and 6 months, with 26 patients scanned at the 3 years follow up. Only those who completed all three visits were included in the final analysis. Baseline atherosclerotic burden was high with a mean SAS of 15.7 +/- 10.3. No significant progression was present at 6 months (mean SAS 16.4 +/- 10.5, p = 0.67), however there was significant disease progression at 3 years (mean SAS 17.7 +/- 11.5, p = 0.01). Those with atheroma progression at follow-up were less likely to be on statin therapy (79 vs 100 %, p = 0.04), and had significantly higher baseline SAS (17.6 +/- 11.2 vs 10.7 +/- 5.1, p = 0.043). Follow up of atheroma burden is possible with WB-MRA, which can successfully quantify and monitor atherosclerosis progression at 3 years follow-up. PMID- 26809613 TI - An in depth proteomic analysis based on ProteoMiner, affinity chromatography and nano-HPLC-MS/MS to explain the potential health benefits of bovine colostrum. AB - Bovine colostrum (BC), the initial milk secreted by the mammary gland immediately after parturition, is widely used for several health applications. We here propose an off-target method based on proteomic analysis to explain at molecular level the potential health benefits of BC. The method is based on the set-up of an exhaustive protein data bank of bovine colostrum, including the minor protein components, followed by a bioinformatic functional analysis. The proteomic approach based on ProteoMiner technology combined to a highly selective affinity chromatography approach for the immunoglobulins depletion, identified 1786 proteins (medium confidence; 634 when setting high confidence), which were then clustered on the basis of their biological function. Protein networks were then created on the basis of the biological functions or health claims as input. A set of 93 proteins involved in the wound healing process was identified. Such an approach also permits the exploration of novel biological functions of BC by searching in the database the presence of proteins characterized by innovative functions. In conclusion an advanced approach based on an in depth proteomic analysis is reported which permits an explanation of the wound healing effect of bovine colostrum at molecular level and allows the search of novel potential beneficial effects. PMID- 26809614 TI - An improved microbore UHPLC method with electrochemical detection for the simultaneous determination of low monoamine levels in in vivo brain microdialysis samples. AB - The simultaneous determination of the monoamines dopamine (DA), noradrenaline (NA) and serotonin (5-HT) in in vivo microdialysis samples remains challenging because of the low extracellular neurotransmitter levels in different brain regions, specific sample characteristics, and the quest for high temporal resolution and a multi-target strategy in neuropharmacological research. A fast and sensitive microbore (1.0mm i.d. column) UHPLC method coupled to electrochemical detection (ECD) is developed by means of design of experiments with the emphasis on sufficient retention of NA within an acceptable total analysis time. Indeed, NA is the earliest eluting compound and often interferes with the broad solvent front originating from the sample matrix. The sensitive UHPLC-ECD assay (LLOQ of 100pM for NA and 150pM for DA and 5-HT) with an analysis time of 8min for standard solutions and 20min for in vivo microdialysis samples originating from rat hippocampus, prefrontal cortex and striatum, is validated applying accuracy profiles. The combination of in vivo microdialysis and microbore UHPLC-ECD has shown to be particularly suitable for future contributions to neuropharmacological research on the monoaminergic system. PMID- 26809615 TI - Simultaneous enantioselective determination of phenylpyrazole insecticide flufiprole and its chiral metabolite in paddy field ecosystem by ultra-high performance liquid chromatography/tandem mass spectrometry. AB - A novel and sensitive ultra-high performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous enantioselective determination of flufiprole and its hydrolysis metabolite in paddy field ecosystem. The separation and determination were performed using reversed-phase chromatography on a novel cellulose chiral stationary phase, a Lux Cellulose-4 (150 mm * 2.0 mm) column, under isocratic conditions at 0.25 mL/min flow rate. The effects of other four different polysaccharide-based chiral stationary phases (CSPs) on the separation and simultaneous enantioseparation of the two target compounds were also evaluated. The elution orders of the eluting enantiomers were identified by an optical rotation detector. Modified QuEChERS (acronym for Quick, Easy, Cheap, Effective, Rugged and Safe) method and solid-phase extraction (SPE) were used for the enrichment and cleanup of paddy water, rice straw, brown rice and paddy soil samples, respectively. Parameters including the matrix effect, linearity, precision, accuracy and stability were evaluated. Under the optimal conditions, the mean recoveries for all enantiomers from the above four sample matrix were ranged from 83.6% to 107%, with relative standard deviations (RSD) in the range of 1.0-5.8%. Coefficients of determination R(2)>=0.998 were achieved for each enantiomer in paddy water, rice straw, brown rice and paddy soil matrix calibration curves within the range of 5-500 MUg/kg. The limits of quantification (LOQ) for all stereoisomers in the above four matrices were all below 2.0 MUg/kg. The methodology was successfully applied for simultaneously enantioselective analysis of flufiprole enantiomers and their chiral metabolite in the real samples, indicating its efficacy in investigating the environmental stereochemistry of flufiprole in paddy field ecosystem. PMID- 26809616 TI - The automatic use of capillary isoelectric focusing with whole column imaging detection for carbamazepine binding to human serum albumin. AB - The binding of the anticonvulsant drug carbamazepine (CBZ) to human serum albumin, both without (dHSA) and in the presence of fatty acids (HSA) was studied in real time by capillary isoelectric focusing with whole column imaging detection (cIEF-WCID). Reaction mixtures at different CBZ:HSA and CBZ:dHSA molar ratios (0:1/25:1) were prepared in phosphate buffer saline (PBS) solution at a physiological pH (7.4), and incubated for 0-72h at 37 degrees C in a water bath. Application of the cIEF-WCID method allowed for observations on the impact of increasing CBZ:serum albumin molar ratios on isoelectric point (pI) shifts, as well as changes in peak area and absorbance, which serve as evidence of structural alterations occurring in the protein in the presence of CBZ. The obtained cIEF-WCID results indicated that the dynamic process of complex formation is not dependent on incubation time. The presented work allowed for recognition of different types of interactions, as well as for the calculation of association constants that demonstrate the stability of the complex. This study was also designed to examine the possible impact of fatty acids (FAs) on protein stability and drug delivery in blood. PMID- 26809618 TI - Combinatorial synthesis of deuterium-enriched atorvastatin. AB - It becomes more and more difficult to discover a new drug by existing models. The concept of deuteration has gained attention due to its advantages in the study of clinical pharmacokinetics and metabolic profiles. Herein we built a library of deuterated atorvastatins using combinatorial chemistry, and all 16 D-compounds were characterized by 1H NMR, 13C NMR, MS, and elemental analysis. PMID- 26809617 TI - Diagnosis of late-onset Pompe disease and other muscle disorders by next generation sequencing. AB - BACKGROUND: Late-onset Pompe disease (LOPD) is a rare treatable lysosomal storage disorder characterized by progressive lysosomal glycogen accumulation and muscle weakness, with often a limb-girdle pattern. Despite published guidelines, testing for LOPD is often overlooked or delayed in adults, owing to its low frequency compared to other muscle disorders with similar muscle patterns. Next-generation sequencing has the capability to test concurrently for several muscle disorders. This could potentially lead to increased diagnosis of LOPD, disorders with non specific muscle weakness or atypical patients. METHODS: We developed a gene panel to further study its clinical utility in a cohort of patients with suspected muscle disorders. We designed a gene panel to analyze the coding sequences and splice site junctions of GAA causing LOPD, along with 77 other genes causing muscle disorders with overlapping phenotypes. RESULTS: At a median coverage of ~200X (sequences per base), all GAA exons were successfully covered with >20X and only 0.3 % of exons across all genes were <20X. The panel showed an excellent sensitivity (100 %) and specificity (98 %) across all selected genes, using known variations in Pompe patients and controls. We determined its clinical utility by analyzing 34 patients with suspected muscle disorders of undetermined etiology and various muscle patterns, who were referred or followed in neuromuscular and genetics clinics. A putative diagnosis was found in up to 32 % of patients. The gene panel was instrumental in reaching a diagnosis in atypical patients, including one LOPD case. Acid alpha-glucosidase activity was used to confirm the molecular results in all patients. CONCLUSION: This work highlights the high clinical utility of gene panels in patients with suspected muscle disorders and its potential to facilitate the diagnosis of patients showing non-specific muscle weakness or atypical phenotypes. We propose that gene panels should be used as a first-tier test in patients with suspected muscle disorders of undetermined etiology, which could further increase overall diagnosis of muscle conditions, and potentially reduce diagnostic delay. Further studies are necessary to determine the impact of first-tier gene panels on diagnostic delay and on treatment outcome for LOPD. PMID- 26809619 TI - Linking reproduction, locomotion, and habitat use in the Trinidadian guppy (Poecilia reticulata). AB - Pregnancy inhibits locomotion, increases predation risk and may translate into reduced survival. The extent to which animals modify behavior in the wild to compensate for the locomotor costs of pregnancy remains poorly understood. We have investigated how reproductive allocation (RA-the proportion of body mass devoted to reproduction) affects locomotor performance and habitat use in Trinidadian guppy (Poecilia reticulata) populations from low- and high-predation regimes. During steady swimming, females with high RA had increased tail beat amplitudes, indicating increased swimming costs. Females with high RA also exhibited slower escape velocities, which may result in an increased risk of predation. In low-predation localities, females with high RA used habitats with a lower water velocity, suggesting that females may be modifying behavior to offset the locomotor costs of pregnancy. Habitat use in high-predation localities was severely restricted to areas without predators, which had a relatively slower water velocity with little or no variation in current. These results provide a link between the performance-related costs of reproduction and behavior in a natural setting and show that animals may compensate for reproductive traits that constrain locomotor performance by modifying habitat use. PMID- 26809620 TI - The effect of within-year variation in acorn crop size on seed harvesting by avian hoarders. AB - Spatial and temporal variation in resource distribution affect the movement and foraging behavior of many animals. In the case of animal-dispersed trees, numerous studies have addressed masting-the synchronized variation in seed production between years-but the fitness consequences of spatial variation in seed production within a year are unclear. We investigated the effects of variable acorn production in a population of valley oaks (Quercus lobata) on the composition and behavior of the avian-disperser community. We found that western scrub-jays (Aphelocoma californica), high-quality dispersers that store seeds in the ground, were attracted to, and exhibited increased per capita dispersal rates from, trees with large acorn crops. In contrast, acorn woodpeckers (Melanerpes formicivorus), low-quality dispersers that store acorns in trees where they are unlikely to germinate, increased per capita hoarding rates but did not attend trees with large seed crops in higher numbers, suggesting that the two species responded to resources on different spatial scales. Antagonistic interactions within and between species increased with the number of birds attending a tree, resulting in a potential cost for foraging birds, but did not reduce dispersal rates. Using a simulation model, we estimated that trees with large initial crops experienced a greater proportion (77 %) of high-quality seed dispersal events than trees with small crops (62 %). Our findings provide support for a mechanistic link between seed production and foraging behavior of seed dispersers as predicted by the predator dispersal hypothesis for the functional consequences of variable seed production in hoarder-dispersed trees. PMID- 26809621 TI - Diurnal adjustment in ultraviolet sunscreen protection is widespread among higher plants. AB - The accumulation of ultraviolet (UV)-absorbing compounds (flavonoids and related phenylpropanoids) in the epidermis of higher plants reduces the penetration of solar UV radiation to underlying tissues and is a primary mechanism of acclimation to changing UV conditions resulting from ozone depletion and climate change. Previously we reported that several herbaceous plant species were capable of rapid, diurnal adjustments in epidermal UV transmittance (T UV), but how widespread this phenomenon is among plants has been unknown. In the present study, we tested the generality of this response by screening 37 species of various cultivated and wild plants growing in four locations spanning a gradient of ambient solar UV and climate (Hawaii, Utah, Idaho and Louisiana). Non destructive measurements of adaxial T UV indicated that statistically significant midday decreases in T UV occurred in 49 % of the species tested, including both herbaceous and woody growth forms, and there was substantial interspecific variation in the magnitude of these changes. In general, plants in Louisiana exhibited larger diurnal changes in T UV than those in the other locations. Moreover, across all taxa, the magnitude of these changes was positively correlated with minimum daily air temperatures but not daily UV irradiances. Results indicate that diurnal changes in UV shielding are widespread among higher plants, vary both within and among species and tend to be greatest in herbaceous plants growing in warm environments. These findings suggest that plant species differ in their UV protection "strategies" though the functional and ecological significance of this variation in UV sunscreen protection remains unclear at present. PMID- 26809622 TI - Phenol Dearomatization with Hypervalent Iodine Reagents. AB - This chapter highlights recent developments in phenol dearomatization using organoiodane reagents and a selection of applications in natural product synthesis. PMID- 26809623 TI - Halogen Bonding in Hypervalent Iodine Compounds. AB - Halogen bonds occur when electrophilic halogens (Lewis acids) attractively interact with donors of electron density (Lewis bases). This term is commonly used for interactions undertaken by monovalent halogen derivatives. The aim of this chapter is to show that the geometric features of the bonding pattern around iodine in its hypervalent derivatives justify the understanding of some of the longer bonds as halogen bonds. We suggest that interactions directionality in ionic and neutral lambda(3)-iodane derivatives is evidence that the electron density distribution around iodine atoms is anisotropic, a region of most positive electrostatic potential exists on the extensions of the covalent bonds formed by iodine, and these positive caps affect, or even determine, the crystal packing of these derivatives. For instance, the short cation-anion contacts in ionic lambda(3)-iodane and lambda(5)-iodane derivatives fully match the halogen bond definition and geometrical prerequisites. The same holds for the short contacts the cation of ionic lambda(3)-iodanes forms with lone-pair donors or the short contacts given by neutral lambda(3)-iodanes with incoming nucleophiles. The longer and weaker bonds formed by iodine in hypervalent compounds are usually called secondary bondings and we propose that the term halogen bond can also be used. Compared to the term secondary bond, halogen bond may possibly be more descriptive of some bonding features, e.g., its directionality and the relationships between structure of interacting groups and interaction strength. PMID- 26809624 TI - Systematic screening of soluble expression of antibody fragments in the cytoplasm of E. coli. AB - BACKGROUND: Disulfide bonds are the most common structural, post-translational modification found in proteins. Antibodies contain up to 25 disulfide bonds depending on type, with scFv fragments containing two disulfides and Fab fragments containing five or six disulfide bonds. The production of antibody fragments that contain native disulfide bonds can be challenging, especially on a large scale. The protein needs to be targeted to prokaryotic periplasm or the eukaryotic endoplasmic reticulum. These compartments are specialised for disulfide bond formation, but both compartments have limitations. RESULTS: Here we show that the introduction into the cytoplasm of a catalyst of disulfide bond formation and a catalyst of disulfide bond isomerization allows the efficient formation of natively folded scFv and Fab antibody fragments in the cytoplasm of Escherichia coli with intact reducing pathways. Eleven scFv and eleven Fab fragments were screened and ten of each were obtained in yields of >5 mg/L from deep-well plates. Production of eight of the scFv and all ten of the Fab showed a strong dependence on the addition of the folding factors. Yields of purified scFv of up to 240 mg/L and yields of purified Fab fragments of up to 42 mg/L were obtained. Purified fragments showed circular dichroism spectra consistent with being natively folded and were biologically active. CONCLUSIONS: Our results show that the efficient production of soluble, biologically active scFv and Fab antibody fragments in the cytoplasm of E. coli is not only possible, but facile. The required components can be easily transferred between different E. coli strains. PMID- 26809625 TI - [Minimal Change Esophagitis]. AB - Gastroesophageal reflux disease (GERD) is defined as a condition which develops when the reflux of gastric contents causes troublesome symptoms and long-term complications. GERD can be divided into erosive reflux disease and non-erosive reflux disease based on endoscopic findings defined by the presence of mucosal break. The Los Angeles classification excludes minimal changes as an evidence of reflux esophagitis because of poor interobserver agreement. In the Asian literature, minimal changes are considered as one of the endoscopic findings of reflux esophagitis, but the clinical significance is still controversial. Minimal change esophagitis is recognized quite frequently among patients with GERD and many endoscopists recognize such findings in their clinical practice. This review is intended to clarify the definition of minimal change esophagitis and their histology, interobserver agreement, and symptom association with GERD. PMID- 26809626 TI - [Endoscopic Resection of Sporadic Non-ampullary Duodenal Neoplasms: A Single Center Study]. AB - BACKGROUND/AIMS: Sporadic non-ampullary duodenal neoplasms are rare and optimal treatment for these lesions remains undefined. Endoscopic resection of duodenal neoplasms is widely used recently and it is an alternative treatment strategy to surgical excision. This study aimed to evaluate the safety and efficacy of endoscopic resection of duodenal neoplasms and to determine its outcomes. METHODS: Patients who underwent endoscopic resection for non-ampullary duodenal neoplasms between January 2005 and December 2014 were analyzed retrospectively. Data including size, morphology, histology, location and endoscopic procedural technique were reviewed. The main outcome measurements were success rate, complication, recurrence and follow-up assessments. RESULTS: The study included 33 patients with duodenal neoplasms. The mean size of resected lesion was 8.58 mm. The results of histologic examination were as follows: 23 (69.7%) adenomas, 2 (6.1%) adenocarcinoma, 3 (9.1%) Brunner's gland tumor and 3 (9.1%) neuroendocrine tumor. Tubular adenoma was the most common type (63.6%) of non-ampullary duodenal neoplasms. Eighteen (54.5%) lesions were found in the second portion of the duodenum, and 10 (30.3%) lesions on bulb and 3 (9.1%) lesions on superior duodenal angle. Of the 33 cases, 32 (97.0%) were managed by endoscopic mucosal resection technique during a single session and one case was managed by endoscopic submucosal dissection (ESD). One episode of perforation occurred after ESD. During a median follow-up period of 5.76 months, recurrence was observed in only one case of in a patient with tubular adenoma. CONCLUSIONS: Endoscopic resection of duodenal neoplasm is a safe and effective treatment modality that can replace surgical resection in many cases. Careful endoscopic follow-up is essential to manage recurrence or residual lesions. PMID- 26809627 TI - [Can Glasgow-Blatchford Score and Pre-endoscopic Rockall Score Predict the Occurrence of Hypotension in Initially Normotensive Patients with Non-variceal Upper Gastrointestinal Bleeding?]. AB - BACKGROUND/AIMS: The aim of this study was to identify the ability of Glasgow Blatchford score (GBS) and pre-endoscopic Rockall score (pre-E RS) to predict the occurrence of hypotension in patients with non-variceal upper gastrointestinal bleeding who are initially normotensive at emergency department. METHODS: Retrospective observational study was conducted at Asan Medical Center emergency department (ED) in patients who presented with non-variceal upper gastrointestinal bleeding from January 1, 2011 to December 31, 2013. Study population was divided according to the development of hypotension, and demographics, comorbidities, and laboratory findings were compared. GBS and pre-E RS were estimated to predict the occurrence of hypotension. RESULTS: A total of 747 patients with non-variceal upper gastrointestinal bleeding were included during the study period, and 120 (16.1%) patients developed hypotension within 24 hours after ED admission. The median values GBS and pre-E RS were statistically different according to the occurrence of hypotension (8.0 vs. 10.0, 2.0 vs. 3.0, respectively; p<0.001). In the receiver operating characteristic curve analysis of hypotension development, the area under the curve of GBS and pre-E RS were 66% and 64%, respectively. The sensitivity and the specificity of GBS using optimal cut-off value were 81% and 46%, respectively, while those based on the pre-E RS were 74% and 46%, respectively. CONCLUSIONS: GBS and pre-E RS were both not sufficient for predicting the occurrence of hypotension in non-variceal upper gastrointestinal bleeding. Development of other scoring systems are needed. PMID- 26809628 TI - [Efficacy of Lactose-free Milk in Korean Adults with Lactose Intolerance]. AB - BACKGROUND/AIMS: Lactose-free milk (LFM) is available for nutrient supply for those with lactose intolerance (LI). However, there are no consistent results of the efficacy of LFM in LI subjects. We aimed to examine the changes of gastrointestinal (GI) symptoms and hydrogen breath test (HBT) values after ingestion of lactose contained milk (LCM) vs. LFM. METHODS: From May 2015 to September 2015, thirty-five healthy adults with history of LCM-induced GI symptoms were recruited at a tertiary hospital. For the diagnosis of LI, HBT with LCM 550 mL (lactose 25 g) was performed every 20 minutes for 3 hours. The test was defined as "positive" when H2 peak exceeded 20 ppm above baseline values (DeltaH2>20 ppm). When the subjects are diagnosed as LI, the second HBT using LFM 550 mL (lactose 0 g) was performed 7 days later. Subjects were asked to complete a questionnaire about the occurrence and severity of GI symptoms. RESULTS: Among a total of 35 subjects, 31 were diagnosed with LI at first visit, and their LCM related symptoms were abdominal pain (98.6%), borborygmus (96.8%), diarrhea (90.3%), and flatus (87.1%). The DeltaH2 value in subjects taking LCM (103.7+/ 66.3ppm) significantly decreased to 6.3+/-4.9 ppm after ingesting LFM (p<0.0001). There were also significant reduction in total symptom scores and the severity of each symptom when LCM was changed to LFM (p<0.0001). CONCLUSIONS: This is the first report that LFM reduce LCM-related GI symptoms and H2 production in Korean adults. LFM can be an effective alternative for LCM in adults with LI. PMID- 26809629 TI - Predictive Factors for Sustained Remission after Discontinuation of Antiviral Therapy in Patients with HBeAg-positive Chronic Hepatitis B. AB - BACKGROUND/AIMS: The optimal timing for discontinuing oral antiviral therapy in patients with HBeAg-positive chronic hepatitis B (CHB) is unclear. The aim of our study was to investigate sustained remission after stopping antiviral therapy in patients with HBeAg-positive CHB. METHODS: We analyzed the medical records of 58 patients who were HBeAg-positive and had discontinued antiviral therapy. Antiviral therapy was discontinued after HBeAg seroconversion and HBV DNA negativity for 6-12 months with consolidation therapy. Virologic relapse was defined as an increase in serum HBV DNA >2,000 IU/mL. RESULTS: No difference was observed between the virologic non-relapse and virologic relapse groups in baseline HBV DNA level (p=0.441) or duration of seroconversion (p=0.070). Time-to undetectable HBV DNA during treatment was shorter in the virologic non-relapse group (29 patients) compared to the relapse group (29 patients) (4.9+/-2.6 vs. 13.2+/-12.7 months; p<0.01). Cumulative relapse rates were 12.7 in month 3, 32.7 in month 6, 47.3 in month 12, and 52.7% in month 18. We determined by multivariate analysis that the consolidation period (>=18 months, p=0.020) and early virologic response (HBV DNA <20 IU/mL) at six months during antiviral therapy (p=0.017) were significant predictors for sustained remission. CONCLUSIONS: A consolidation period of at least 18 months and early virological response at six months during antiviral therapy were associated with sustained remission in patients with HBeAg-positive CHB after treatment. PMID- 26809630 TI - [Management of Intramural Esophageal Dissection with Gastric Feeding Tube in an Alcoholic-hepatitis Patient]. AB - Intramural esophageal dissection is a rare but clinically important condition in the field of gastroenterology. Classically, intramural esophageal dissection rarely occurs in patients who are anticoagulated or have poor medical condition, and its clinical presentation may include chest pain, dysphagia and hematemesis. Herein, we present a case of intramural esophageal dissection in an alcoholic hepatitis patient that was diagnosed by endoscopy and successfully treated with conservative management. PMID- 26809631 TI - [A Case of Severe Chronic Active Epstein-Barr Virus Infection with Aplastic Anemia and Hepatitis]. AB - Epstein-Barr virus (EBV) causes various acute and chronic diseases. Chronic active EBV infection (CAEBV) is characterized by infectious mononucleosis-like symptoms that persist for more than 6 months with high viral loads in peripheral blood and/or an unusual pattern of anti-EBV antibodies. Severe CAEBV is associated with poor prognosis with severe symptoms, an extremely high EBV related antibody titer, and hematologic complications that often include hemophagocytic lymphohistiocytosis. However, CAEBV which led to the development of aplastic anemia (AA) has not been reported yet. A 73-year-old woman was admitted to our hospital with intermittent fever, general weakness and elevated liver enzymes. In the serologic test, EBV-related antibody titer was elevated, and real-time quantitative-PCR in peripheral blood showed viral loads exceeding 10(4) copies/MUg DNA. Liver biopsy showed characteristic histopathological changes of EBV hepatitis and in situ hybridization with EBV-encoded RNA-1 was positive for EBV. Pancytopenia was detected in peripheral blood, and the bone marrow aspiration biopsy showed hypocellularity with replacement by adipocytes. AA progressed and the patient was treated with prednisolone but deceased 8 months after the diagnosis due to multiple organ failure and opportunistic infection. Herein, we report a rare case of severe CAEBV in an adult patient accompanied by AA and persistent hepatitis. PMID- 26809632 TI - Multiple Pyogenic Liver Abscesses Caused by Microperforation of an Idiopathic Cecal Ulcer. AB - Idiopathic cecal ulcer is a rare disease entity of unknown cause diagnosed by ruling out other known causes of cecal ulceration. The most common complication of an idiopathic cecal ulcer is bleeding; perforation, peritonitis, abscess, and stricture formation have been noted. The authors treated a 53-year-old woman who presented with fever and intermittent right upper quadrant abdominal pain. Multiple pyogenic liver abscess and a solitary cecal ulcer were diagnosed by radiologic, endoscopic, and pathologic examination, followed by laparoscopic cecectomy. After extensive study, we concluded that this patient's liver abscesses were a complication of the idiopathic cecal ulcer. Herein, we report a case of multiple pyogenic liver abscess caused by microperforation of idiopathic cecal ulcer. PMID- 26809633 TI - A Case of Ciliated Foregut Cyst of the Gallbladder. AB - Congenital cysts of the gallbladder are extremely rare, hence only a few ciliated foregut cysts of gallbladder have been reported. We report a case of a 20-year old woman presenting with mild right upper quadrant abdominal discomfort, with normal levels of serum bilirubin and liver function tests. Abdominal ultrasonography revealed a well-defined cystic mass measured about 2 cm attached to the neck of gallbladder, with internal echogenic debris suggesting a complicated cyst, such as a hemorrhagic cyst. Abdominal computed tomography and magnetic resonance cholangiopancreatography revealed similar findings. Laparoscopic cholecystectomy showed a slightly distended gallbladder. The size of cyst on the neck was 1.6*1.2 cm, and it contained mucosa lined by ciliated pseudostratified columnar epithelium and underlying smooth muscle layers. Histopathology identified a ciliated foregut cyst of gallbladder. PMID- 26809634 TI - A cross-sectional study of 329 farms in England to identify risk factors for ovine clinical mastitis. AB - The aims of this study were to estimate the incidence rate of clinical mastitis (IRCM) and identify risk factors for clinical mastitis in suckler ewes to generate hypotheses for future study. A postal questionnaire was sent to 999 randomly selected English sheep farmers in 2010 to gather data on farmer reported IRCM and flock management practices for the calendar year 2009, of which 329 provided usable information. The mean IRCM per flock was 1.2/100 ewes/year (CI:1.10:1.35). The IRCM was 2.0, 0.9 and 1.3/100 ewes/year for flocks that lambed indoors, outdoors and a combination of both, respectively. Farmers ran a variety of managements before, during and after lambing that were not comparable within one model, therefore six mixed effects over-dispersed Poisson regression models were developed. Factors significantly associated with increased IRCM were increasing percentage of the flock with poor udder conformation, increasing mean number of lambs reared/ewe and when some or all ewes lambed in barns compared with outdoors (Model 1). For ewes housed in barns before lambing (Model 2), concrete, earth and other materials were associated with an increase in IRCM compared with hardcore floors (an aggregate of broken bricks and stones). For ewes in barns during lambing (Model 3), an increase in IRCM was associated with concrete compared with hardcore flooring and where bedding was stored covered outdoors or in a building compared with bedding stored outdoors uncovered. For ewes in barns after lambing (Model 4), increased IRCM was associated with earth compared with hardcore floors, and when fresh bedding was added once per week compared with at a frequency of <=2 days or twice/week. The IRCM was lower for flocks where some or all ewes remained in the same fields before, during and after lambing compared with flocks that did not (Model 5). Where ewes and lambs were turned outdoors after lambing (Model 6), the IRCM increased as the age of the oldest lambs at turnout increased. We conclude that the reported IRCM is low but highly variable and that the complexity of management of sheep around lambing limits the insight into generating hypotheses at flock level for risks for clinical mastitis across the whole industry. Whilst indoor production was generally associated with an increased IRCM, for ewes with large litter size indoor lambing was protective, we hypothesise that this is possibly because of better nutrition or reduced exposure to poor weather and factors associated with hygiene. PMID- 26809635 TI - KiSS-1 expression in oral squamous cell carcinoma and its prognostic significance. AB - Downregulated expression of KiSS-1 has been correlated with tumor progression, metastasis, and patient prognosis in various human malignancies. However, there is no information regarding the expression of KiSS-1 in oral squamous cell carcinoma (OSCC). Our aims were to examine KiSS-1 expression in OSCC tissue samples and cell lines and to determine its prognostic significance. KiSS-1 expression was significantly lower in lymph node (LN) metastases than in primary tumor tissues. Five of six OSCC cell lines showed absence or relatively low expression of KiSS-1. Correlations between KiSS-1 expression and clinicopathological parameters were statistically assessed. There were significant correlations between KiSS-1 expression and LN metastasis (p = 0.007), TNM stage (p = 0.024), and local recurrence (p = 0.012). In the Kaplan-Meier survival analysis, negative KiSS-1 expression significantly correlated with poorer overall survival (OS) and disease-free survival (DFS) (p = 0.000 and 0.000, respectively). Multivariate analysis using Cox regression modeling revealed that KiSS-1 expression was an independent prognostic factor for both OS and DFS (p = 0.001 and 0.000, respectively). Our findings suggested that KiSS-1 downregulation may play a role in tumor progression and metastasis of OSCC and may be a reliable biomarker for predicting clinical outcome in OSCC. PMID- 26809637 TI - Toxic effects, metabolism, and carry-over of ergot alkaloids in laying hens, with a special focus on changes of the alkaloid isomeric ratio in feed caused by hydrothermal treatment. AB - Ergot alkaloids (EA) are mycotoxins formed by Claviceps purpurea. Due to the large variation in EA content, the mass proportion of ergot (hardened sclerotia) in animal diets is not suited to establish safe levels of EA. Therefore, the aim of the present study was to examine the dose-dependent effects of dietary EA on laying hens. Ergoty rye or ergot-free rye (control diet) was included in the diets either untreated or after hydrothermal treatment ("expansion"). The total EA levels in five different diets containing 0-3% of untreated or expanded rye were 0.1-14.56 mg/kg (untreated rye) and 0.08-13.03 mg/kg (expanded rye). The average EA reduction amounted to 11% due to expanding. The proportions of the sum of all -inine isomers however were consistently higher (19.5-48.4%) compared to the sum of their -ine isomer counterparts which decreased at the same time. Most of the laying performance and reproductive traits were significantly compromised during the test period between weeks 22 and 42 of age when the diet with the highest EA content was fed. Toxic effects were less pronounced due to expanding. Relative weights of liver, proventriculus, and gizzard as well as the aspartate aminotransferase activity, the antibody titers to Newcastle disease virus, albumin, and total bilirubin concentrations were all significantly increased in hens fed at the highest dietary ergot level whereby expanding additionally modified the albumin and total bilirubin responses. No carry-over of EA into egg yolk and albumen, blood, liver, and breast muscle was found, but bile contained quantifiable levels of ergometrine and ergometrinine. Biological recovery of ingested individual alkaloids with the excreta varied from 2 to 22% and was strongly positive linearly related to the octanol to water partition coefficient (logkOW). This suggests the lipophilicity of alkaloids as a factor influencing their metabolism and elimination. Based on the overall results of this study, a lowest observed adverse effect level (LOAEL) of 14.56 mg EA/kg for laying hen diets can be proposed, while the no observed adverse effect level (NOAEL) corresponds to a dietary EA level of 3.72 mg/kg. However, it must be stressed that these critical levels apply for the specific EA pattern tested in the present experiment, while batches of ergot containing a less typical alkaloid composition, or other expanding conditions, might contribute to variations in the LOAEL/NOAEL. PMID- 26809639 TI - PIN Transcriptional Regulation Shapes Root System Architecture. AB - Regulation of auxin distribution by PIN transporters is key in the dynamic modulation of root growth and branching. Three novel papers shed light on an intricate network through which several hormones and transcriptional regulators collectively fine-tune the transcriptional level of these auxin transporters in the root. PMID- 26809638 TI - Relationship between post-awakening salivary cortisol and melatonin secretion in healthy participants. AB - We report the relationship between patterns of post-awakening salivary melatonin and cortisol secretion in healthy participants (n = 51; mean age 21.6 +/- 5.0 years). Saliva samples were collected within the domestic setting, at 0-, 15-, 30 , and 45-min post-awakening on 2 consecutive typical weekdays. Analyses were undertaken on data with electronically verified sample timing accuracy (<5-min delay between awakening and the start of saliva sampling). Melatonin secretion declined linearly by an average of 29% within the first 45-min post-awakening. In contrast, there was a marked 112% surge in cortisol, characteristic of the cortisol awakening response. No day differences in melatonin or cortisol secretion were observed but melatonin concentrations were lower with later awakening. Despite contrasting post-awakening changes in these hormones, there was a lack of relationship between overall levels or patterns of melatonin and cortisol during this period. PMID- 26809640 TI - Simultaneous Determination of 11 Components in Yinzhihuang Preparations and Their Constituent Herbs by High-Performance Liquid Chromatography with Diode Array Detector. AB - A simple and sensitive liquid chromatography method with diode array detector was established for simultaneous determination of 11 components (geniposidic acid, chlorogenic acid, caffeic acid, geniposide, luteoloside, isochlorogenic acid C, baicalin, luteolin, wogonoside, baicalein and wogonin) in various commercial Yinzhihuang preparations and their herbs by optimizing the extraction, separation and analytical conditions. Eleven components were identified on the basis of their retention times and mass spectra. Chromatographic separation was performed on a C18 analytical column with a gradient elution of acetonitrile and 0.1% formic acid water solution at a flow rate of 1.0 mL/min. The linearity, precision and accuracy of the data obtained were acceptable. The method was used to analyze four Yinzhihuang preparations (powder, capsule, oral liquid and injection) and related herbs (Radix Scutellariae, Flos Lonicerae, Herba Artemisiae Scopariae and Fructus gardeniae). Results suggested that the optimized method could be considered as a good approach to control the quality of Yinzhihuang preparations and their herbs. PMID- 26809645 TI - Synthesis of 1,2-biphenylethane based single-molecule diodes. AB - We have described the synthesis of novel biphenylethane-based wires for molecular electronics. Exceptional single-molecule diode behavior was predicted for unsymmetrically substituted biphenylethane derivatives, synthesized here using the so far unexplored unsymmetrically substituted 1,2-bis(4-bromophenyl)ethanes as key intermediates, which were obtained from the corresponding tolane precursor by selective hydrogenation. PMID- 26809646 TI - Demand for family planning among HIV positive women on ART: the case of South Gondar and North Wollo Zones Amhara region. AB - BACKGROUND: Although family planning for human immune deficiency virus positive women has numerous advantages, evidences in different parts of the world showed the existence of persistent unmet need. There were few studies done in Ethiopia on level of unmet need for family planning among women in reproductive age on antiretroviral therapy (ART). This study was therefore done to determine the level of demand and unmet need for family planning among women on ART in South Gondar and North Wollo Zones, Amhara region. METHODS: Institution based cross sectional study design was used. Data was collected from June 15 to 25, 2013 in South Gondar and North Wollo Zones. Study participants were recruited from six health centers and two hospitals. The study participants were proportionally allocated to the health institutions. Multistage sampling technique was used to recruit study participants. Trained nurses interviewed the respondents using pretested structured Amharic questionnaire. Data was entered, cleaned and analyzed using Statistical Package for Social Science version 16. Ratios and proportions were computed to determine demand and unmet need for family planning. RESULTS: A total of 530 women in reproductive age on ART were interviewed in this study. Two hundred ninety-three women were married. Fourteen (2.6%) women were pregnant at the time of interview. Five of these pregnancies were not planned. In this study, 242 (45.7%) women reported that they were using contraceptives. Most women (74.4%) were using injectable (depo). Among those who were not using contraceptives, 84 (29.2%) reported that they will use in the future. Fifty-two (61.9%) of them said that they will use injectables (depo). In this study, the total demand for family planning among women on ART was 86.7%. From this, 62.1% and 24.6% was met and unmet need respectively. CONCLUSIONS: This study revealed that the level of demand and met need for modern contraceptives among reproductive age women on antiretroviral therapy in South Gondar and North Wollo Zones was higher than that of sexually active married women in Ethiopia. But the level of unmet need is still similar with that of sexually active married women in Ethiopia. PMID- 26809648 TI - Adult pertussis is unrecognized public health problem in Thailand. AB - BACKGROUND: Although pertussis has been considered a disease of childhood, it is also recognized as an important respiratory tract infection in adolescents and adults. However, in countries with routine vaccination against pertussis with high coverage, pertussis is not usually taken into consideration for the etiology of prolonged cough in adults. Previous studies in a variety of populations in developed countries have documented that pertussis is quite common, ranging from 2.9 to 32% of adolescents and adults with prolonged cough. The anticipation and early recognition of this change in the epidemiology is important because the affected adolescents and adults act as reservoirs of the disease and source of infection to the vulnerable population of infants, for whom the disease can be life threatening. We conducted a prospective study to determine the prevalence of pertussis in Thai adults with prolonged cough. METHODS: Seventy-six adult patients with a cough lasting for more than 2 weeks (range, 14-180 days) were included in the present study. The data regarding medical history and physical examination were carefully analyzed. Nasopharyngeal swabs from all patients were obtained for the detection of deoxyribonucleic acid of Bordetella pertussis by the polymerase chain reaction (PCR) method. Paired serum samples were collected and tested for IgG antibody against pertussis toxin by using an ELISA method. RESULTS: Of 76 adult patients, 14 patients (18.4%) with the mean age of 59 (range, 28-85) years and the mean duration of cough of 34 (range, 14-120) days had laboratory evidence of acute pertussis infection. One patient was diagnosed by the PCR method, while the rest had serological diagnosis. Whooping cough is a significantly associated symptom of patients with chronic cough who had laboratory evidence of pertussis. (p < .05, odds ratio 3.75, 95% confidence interval: 1.00, 14.06) CONCLUSION: Pertussis is being increasingly recognized as a cause of prolonged, distressing cough among adults in Thailand. This result addresses the need of pertussis vaccination in Thai adults for preventing transmission to a high risk group such as newborn infants. PMID- 26809651 TI - Biopsy-proven IgG4-related lung disease. AB - BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory disorder that may involve single or multiple organs. Biopsy-proven lung involvement of this disease is occasionally reported, but not well understood. METHODS: Patients with the diagnosis of biopsy-proven IgG4-related lung disease (IgG4-RLD) from Peking Union Medical College Hospital between January 2011 and July 2015 were retrospectively analyzed. Age, sex, clinical symptoms, laboratory findings, pulmonary function test results, chest CT tests, positron emission tomography (PET) examinations, treatments and prognoses were retrieved from medical records and analyzed. RESULTS: Seventeen patients were included in this study (mean age: 44.8 +/- 15.0 years). Ten patients were diagnosed via surgery, and 7 patients were diagnosed via percutaneous transthoracic core-needle lung biopsy. Extrapulmonary involvement was observed in only one patient. The clinical symptoms included cough, fever, dyspnea, chest pain and hemoptysis. The serum IgG4 concentration was elevated in 7/13 patients (mean: 1955 +/- 1968 mg/L). The chest CT findings included mainly nodules and masses with spiculated borders, alveolar consolidations with air bronchograms, and ground glass opacities with or without reticular opacities. PET scans indicated increased standardized uptake values, and 7/8 patients were correctly diagnosed with benign inflammation. Corticosteroids and immunosuppressants were administered to 14/17 patients and effectively alleviated the disease. CONCLUSIONS: In biopsy-proven IgG4-RLD, a normal serum IgG4 concentration is commonly seen, while extrapulmonary involvement is infrequent. Alveolar consolidation with air bronchograms is an important imaging finding of IgG4-RLD, which has not been emphasized before. PMID- 26809652 TI - GILT--A randomised phase III study of oral vinorelbine and cisplatin with concomitant radiotherapy followed by either consolidation therapy with oral vinorelbine and cisplatin or best supportive care alone in stage III non-small cell lung cancer. AB - BACKGROUND: Concurrent chemoradiotherapy (CRT) is considered standard for inoperable stage III non-small cell lung cancer (NSCLC). Consolidation chemotherapy (CC) following CRT is intended to further improve outcomes, yet studies have shown discordant results. This phase III study assessed CRT followed by best supportive care (BSC) or consolidation with oral vinorelbine and cisplatin. METHODS: Patients received two cycles of oral vinorelbine (50 mg/m(2) days 1, 8 and 15) + cisplatin (20 mg/m(2) days 1-4) q4w + radiotherapy (RT; 66 Gy). Patients with at least stable disease (SD) were randomised to either two cycles oral vinorelbine (60-80 mg/m(2) days 1 and 8) + cisplatin (80 mg/m(2) day 1) q3w + BSC or BSC alone. Primary endpoint was progression-free survival (PFS). RESULTS: A total of 279 patients were enrolled for CRT and 201 patients were randomised to CC or BSC. Both CRT and CC were well tolerated, with limited radiation-mediated grade 3/4 toxicities (CRT/CC/BSC: oesophagitis-related events 12.9 %/3.1 %/0 %; grade 3 pneumonitis 0 %/0 %/2 %) and chemotherapy-mediated grade 3/4 toxicities (CRT/CC: neutropenia 11.2 %/22.1 %; leukopenia 18.3 %/26.7 %; grade 3 nausea 5.0 %/2.3 %, grade 3 vomiting 3.2 %/3.5 %). Median PFS from randomisation was 6.4 (5.0-8.7) and 5.5 (3.8-7.4) months in the CC and BSC arms (hazard ratio, HR = 0.93 [0.69-1.26]; p = 0.63), respectively; median overall survival (OS) 20.8 (13.5-25.3) and 18.5 (13.6-24.7) months, respectively. DISCUSSION: Consolidation chemotherapy after concurrent CRT did not prolong PFS or OS. Concurrent RT with oral vinorelbine and cisplatin demonstrated a favourable safety profile and represents a suitable treatment regimen for inoperable stage III NSCLC. PMID- 26809653 TI - Morphological Effects and Antioxidant Capacity of Solanum crispum (Natre) In Vitro Assayed on Human Erythrocytes. AB - In order to gain insight into the molecular mechanism of the antioxidant properties of Solanum crispum, aqueous extracts of its leaves were assayed on human erythrocytes and molecular models of its membrane. Phenolics and alkaloids were detected by HPLC-MS. Scanning electron and defocusing microscopy showed that S. crispum changed erythrocytes from the normal shape to echinocytes. These results imply that molecules present in the aqueous extracts were located in the outer monolayer of the erythrocyte membrane. Dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) were chosen as representative of phospholipid classes located in the outer and inner monolayers of the erythrocyte membrane, respectively. X-ray diffraction showed that S. crispum preferentially interacted with DMPC bilayers. Experiments regarding its antioxidant properties showed that S. crispum neutralized the oxidative capacity of HClO on DMPE bilayers; defocusing microscopy and hemolysis assays demonstrated the protective effect of S. crispum against the oxidant effects of HClO on human erythrocytes. PMID- 26809654 TI - Effects of UVB Radiation on the Physicochemical Properties of Fibroblasts and Keratinocytes. AB - The skin is the largest human organ, providing the first line of defense to protect the body from physical and environmental effects. The aim of this study was to determine the influence of short-wave ultraviolet (UVB) radiation on the membrane electrical properties, phospholipid content, and lipid peroxidation levels of fibroblasts and keratinocytes. Changes in cell function may affect the basal electrical surface properties of cell membranes. These changes can be detected using electrokinetic measurements. In this study, the surface charge densities of fibroblasts and keratinocytes were measured as a function of pH. A four-component equilibrium model was used to describe the interaction between the ions in solution and on cell membrane surfaces. Agreement was found between the experimental and theoretical charge variation curves of leukemia cells from pH 2.5 to pH 9. Phospholipid composition was determined qualitatively and quantitatively by HPLC, and lipid peroxidation was estimated by measuring the level of malondialdehyde. The acidic functional group concentrations and average association constants with hydroxyl ions were higher, and the average association constants with hydrogen ions were smaller in UVB-treated skin cell membranes compared to those in untreated cells. Moreover, our results showed that UVB radiation is associated with increased levels of phospholipids and lipid peroxidation products in fibroblasts and keratinocytes. PMID- 26809655 TI - Mechanism of aortic root dilation and cardiovascular function in tetralogy of Fallot. AB - The aortic root dilation in tetralogy of Fallot (TOF) is a long-term clinical problem, because a severely dilated aorta can lead to aortic regurgitation, dissection, or rupture, which can be fatal, necessitating surgical intervention. The details of the mechanism of aortic root dilation, however, are unclear. We have shown that aortic stiffness is increased in patients with repaired TOF, and may mirror the histological abnormality of elastic fiber disruption and matrix expansion. This aortic stiffness is related closely to the aortic dilation, indicating that aortic stiffness may be a predictor of outcome of aortic dilation. Furthermore, the aortic volume overload is a very important determinant of aortic diameter in TOF patients before corrective surgery. In addition, a chromosomal abnormality and the transforming growth factor-beta signaling pathway, a major contributor to aortic dilation in Marfan syndrome, also affect this mechanism. In this way, aortic dilation in TOF patients is suggested to be a multifactorial disorder. The aim of this review was therefore to clarify the mechanism of aortic dilation in TOF, focusing on recent research findings. Studies linking histopathology, mechanical properties, molecular/cellular physiology, and clinical manifestations of aortic dilation facilitate appropriate treatment intervention and improvement of long-term prognosis of TOF. PMID- 26809656 TI - Perovskite-organic hybrid tandem solar cells using a nanostructured perovskite layer as the light window and a PFN/doped-MoO3/MoO3 multilayer as the interconnecting layer. AB - In this study, we present a two-terminal perovskite (PVSK)-organic hybrid tandem solar cell with a nanostructured PVSK as the light window and a PFN/doped MoO3/MoO3 structure as the interconnecting layer (ICL). In this tandem structure, the PVSK layer is specially designed with a nanostructured surface morphology; thus the PCBM could be filled-up for forming intimately contacted interface with PVSK layers. This design could not only efficiently increase the device performance, it could also greatly remove the hysteresis of PVSK solar cells. The study indicates that doped MoO3 as the step layer plays a key role in protecting the underlying layer against multi-solution processes and aids in the efficient recombination of electrons and holes generated from the sub-cells. The hybrid tandem solar cell could achieve a high VOC of 1.58 V, which is the sum of those in the two sub-cells, and a high FF of 0.68, indicating the effectiveness of the multilayer ICL. PMID- 26809657 TI - SIRB, sans iron oxide rhodamine B, a novel cross-linked dextran nanoparticle, labels human neuroprogenitor and SH-SY5Y neuroblastoma cells and serves as a USPIO cell labeling control. AB - This is the first report of the synthesis of a new nanoparticle, sans iron oxide rhodamine B (SIRB), an example of a new class of nanoparticles. SIRB is designed to provide all of the cell labeling properties of the ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle Molday ION Rhodamine B (MIRB) without containing the iron oxide core. MIRB was developed to label cells and allow them to be tracked by MRI or to be manipulated by magnetic gradients. SIRB possesses a similar size, charge and cross-linked dextran coating as MIRB. Of great interest is understanding the biological and physiological changes in cells after they are labeled with a USPIO. Whether these effects are due to the iron oxide buried within the nanoparticle or to the surface coating surrounding the iron oxide core has not been considered previously. MIRB and SIRB represent an ideal pairing of nanoparticles to identify nanoparticle anatomy responsible for post-labeling cytotoxicity. Here we report the effects of SIRB labeling on the SH SY5Y neuroblastoma cell line and primary human neuroprogenitor cells (hNPCs). These effects are contrasted with the effects of labeling SH-SY5Y cells and hNPCs with MIRB. We find that SIRB labeling, like MIRB labeling, (i) occurs without the use of transfection reagents, (ii) is packaged within lysosomes distributed within cell cytoplasm, (iii) is retained within cells with no loss of label after cell storage, and (iv) does not alter cellular viability or proliferation, and (v) SIRB labeled hNPCs differentiate normally into neurons or astrocytes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26809659 TI - Cilostazol attenuates gentamicin-induced nephrotoxicity in rats. AB - INTRODUCTION: Gentamycin is a widely used antibiotic. The nephrotoxic adverse effects of the drug may limit its use. Cilostazol, a phosphodiesterase III inhibitor, was reported to protect from renal oxidative stress. This work aimed to investigate the possible protective effect of cilostazol on gentamicin-induced nephrotoxicity and the possible underlying mechanisms. MATERIALS AND METHODS: 40 male albino rats were divided into 4 equal groups: (1) Control; (2) Cilostazol, 10mg/kg, p.o.; (3) Gentamicin, 80 mg/kg, i.p.; (4) Gentamicin 80 mg/kg, i.p. along with cilostazol 10mg/kg, p.o. All drugs were administered once daily for 8 days. On 9th day blood samples were collected for the estimation of creatinine, urea and uric acid in serum. Then the rats were sacrificed and kidneys were removed for light and electron microscope studies. Moreover, reduced glutathione (GSH) and malondialdehyde (MDA) levels as well as catalase (CAT) and superoxide dismutase (SOD) activities were determined in renal tissues. RESULTS: Gentamicin elevated the serum levels of creatinine, urea and uric acid as well as the MDA level in the renal tissue, while it decreased CAT, SOD activities and GSH levels as well as produced degenerative changes in glomeruli and tubules associated with increased expression of apoptotic markers and decreased expression of anti apoptotic markers. Administration of cilostazol decreased urea, creatinine, uric acid and MDA levels while increased CAT and SOD activities and GSH levels as well as ameliorated the histopathological changes in relation to gentamicin group. CONCLUSION: Cilostazol protected rats from gentamicin-induced nephrotoxicity possibly, in part through its antioxidant and anti-apoptotic activity. PMID- 26809660 TI - Gadolinium-based contrast agent anaphylaxis, a unique presentation of acute abdominal pain. PMID- 26809658 TI - Effects of deoxynivalenol on calcium homeostasis of concanavalin A--Stimulated splenic lymphocytes of chickens in vitro. AB - In this study, the in vitro effects of the treatment of concanavalin A (Con A)- stimulated splenic lymphocytes with DON were examined. Splenic lymphocytes isolated from chickens were stimulated with 12.5 MUg/mL Con A and exposed to deoxynivalenol (DON) (0-50 MUg/mL) for 48 h. The intracellular calcium concentration ([Ca(2+)]i), pH, calmodulin (CaM) mRNA levels, and Na(+),K(+) ATPase and Ca(2+)-ATPase activities were detected. With the DON exposure concentrations increased, the [Ca(2+)]i and CaM mRNA levels gradually increased in a dose-dependent manner, and all the evaluated conconcentrations affected ATPase activity to the same extent. There were significant differences (P<0.05 or P<0.01) between the treatment groups and the control group. These results indicate that an imbalance in calcium homeostasis and intracellular acidification are components of DON cytotoxicity in chicken lymphocytes. PMID- 26809661 TI - Isolated dorsal dislocations of the talonavicular and calcaneocuboid articulations (Chopart joints) from a low-energy mechanism. PMID- 26809662 TI - Endotracheal intubation with tactical fiberoptic imaging systems. PMID- 26809666 TI - Nocardiosis following hematopoietic stem cell transplantation. AB - BACKGROUND: Nocardia species are ubiquitous environmental organisms that can cause a diverse spectrum of disease. Clinical manifestations range from localized skin and soft tissue infections to life-threatening pulmonary, central nervous system, and/or disseminated infections. Patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT) are at risk for nocardiosis, and further data in regard to characteristics of disease in this population are warranted. METHODS: We performed retrospective chart review of patients post allogeneic HSCT at Moffitt Cancer Center in Florida diagnosed with nocardiosis from 2003 to 2013. RESULTS: In a decade, 15 cases of nocardiosis were identified. The majority of patients were men (11/15). The median age was 55 years (range 25-65). The most common type of transplant was matched-related donor (n = 8), followed by matched-unrelated donor (n = 3), mismatched-unrelated donor (n = 3), and double umbilical cord (n = 1). Ten received myeloablative conditioning (MAC) regimens. Twelve of 15 patients were on prednisone, 10 of which were on a total daily dose >=20 mg. The median time from transplant to first positive culture was 10 months (range 1.5-93). Pulmonary nocardiosis was the most prevalent manifestation at 87%. Disseminated disease (2 or more sites of infection) was seen in 47%, whereas blood cultures were positive in 27% of the total cohort. The most common species was Nocardia nova (n = 4). At the time of diagnosis, 20% of the patients were receiving prophylaxis for Pneumocystis jirovecii pneumonia (PJP) with trimethoprim-sulfamethoxazole (TMP-SMX). Susceptibility data were available for 8 patients: all 8 samples were susceptible to TMP-SMX. Nocardiosis was treated with 2 or more active drugs in 93% of the patients. Overall mortality was 53%, with nocardiosis attributed as the cause in 62.5% (5/8). The absolute lymphocyte count at time of diagnoses was significantly lower in patients who ultimately experienced treatment failure. CONCLUSION: Infection with Nocardia species in allogeneic HSCT recipients appears to be a late complication of transplantation and most commonly involves the lung. Two thirds of the cohort received a MAC regimen and the majority of the patients were receiving steroids at the time of diagnosis. Most patients were not receiving TMP SMX for PJP prophylaxis at the time of nocardiosis diagnosis, and TMP-SMX may therefore have a protective effect. PMID- 26809667 TI - Review on the clinical use of eribulin mesylate for the treatment of breast cancer. AB - INTRODUCTION: Breast cancer is the second leading cause of cancer death among women and the median survival of metastatic breast cancer (MBC) has remained, for many decades, at two to three years after diagnosis. Eribulin mesylate is a nontaxane inhibitor of microtubule dynamics and the only cytotoxic agent in the last decade to improve overall survival in heavily pretreated patients with MBC. Eribulin was approved for the treatment of MBC in 2010 by the FDA in patients that received at least two prior chemotherapy regimens and as second-line treatment in 2011 by EMA. In both cases prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting. AREAS COVERED: This manuscript reviews the current available data on the use of this important cytotoxic agent including its pharmacology, pharmacokinetics, clinical efficacy, safety, and potential economic factors as well as ongoing clinical trials and main areas of research. EXPERT OPINION: Eribulin mesylate is a novel microtubule dynamics inhibitor compound important for the management of MBC and can be used for the treatment of patients who have previously received one/two chemotherapeutic regimens for metastatic disease and whose prior therapy included an anthracycline and a taxane. It's toxicity profile is acceptable and presents several favorable features namely a low probability of drug-drug interactions in the clinical setting, easy administration as bolus, low hypersensitivity chances and full tolerability in renal dysfunction patients. Eribulin is currently being evaluated as first-line treatment for MBC, in the adjuvant/neoadjuvant setting alone and in combination with a variety of agents, particularly biologic treatments. Future research is needed to optimize the role of eribulin in the treatment of MBC. PMID- 26809668 TI - Commentary on models of biobanks and implications for reproductive health innovation. PMID- 26809670 TI - Clinical application of a three-dimensional imaging technique in infants and young children with complex liver tumors. AB - INTRODUCTION: Three-dimensional (3D) imaging instead of two-dimensional (2D) computed tomography (CT) for diagnosis and preoperative planning in infants and young children with complex liver tumors is a promising technique for precision hepatectomy. METHODS: This study was a retrospective analysis of 26 infants and young children with giant liver tumors involving the hepatic hilum who underwent precise hepatectomy at the Affiliated Hospital of Qingdao University between February 2012 and January 2015. All patients received upper abdominal contrast enhanced CT scanning before surgery. 16 patients used Hisense CAS system for 3D reconstruction as the reconstruction group. While ten patients underwent 3D CT reconstruction by the CT Workstation as the control group. The clinical outcomes were analyzed and compared between the two groups. The 3D reconstruction of abdominal organs and blood vessels was generated using the Hisense CAS system. Diagnosis and preoperative planning assisted by the system was used for preoperative and intraoperative decision-making for precise hepatectomy. RESULTS: All patients underwent successful surgery. The 3D models clearly demonstrated the association of liver tumors with the intrahepatic vascular system and provided a preoperative assessment of resectability, assisting surgeons in preoperative procedural planning. Anatomic hepatectomy was successfully completed in the reconstruction group. The mean operation time was shorter in the reconstruction group (137.81 +/- 17.51 min) than in the control group (192 +/- 34.66 min) (P < 0.01). The mean intraoperative blood loss was lesser in the reconstruction group (21.81 +/- 14.05 ml) than in the control group (53.50 +/- 21.35 ml) (P < 0.01). The difference was statistically significant. DISCUSSION: 2D CT scan images cannot accurately display the spatial relationship between the tumor and surrounding vasculature. The 3D reconstruction model used in this study gave detailed and accurate anatomical information and allowed for the assessment of tumor resectability and provided a detailed road map for preoperative decision making and predicted the postoperative liver function. CONCLUSIONS: 3D visualization technology provides preoperative assessment and allows individualized surgical planning. Surgical controllability, accuracy, and safety can be improved in infants and young children undergoing precise hepatectomy for complex liver tumors. PMID- 26809669 TI - Development of a systematic protocol to identify victims of non-accidental trauma. AB - PURPOSE: Each year, nearly 1 million children in the USA are victims of non accidental trauma (NAT). Missed diagnosis or poor case management often leads to repeat/escalation injury. Victims of recurrent NAT are at higher risk for severe morbidity and mortality resulting from abuse. The objective of this review is to describe the evolution and implementation of this tool and evaluate our institutional response to NAT prior to implementation. METHODS: A systematic guideline for the evaluation of pediatric patients in which NAT is suspected or confirmed was developed and implemented at a level II pediatric trauma hospital. To understand the state of our institution prior to implementation of the guideline, a review of 117 confirmed NAT cases at our hospital over the prior 4 years was conducted. RESULTS: In the absence of a systematic management guideline, important and relevant social and family history red flags were often missing in the initial evaluation. Patients with perineal bruising experienced significantly higher mortality than patients without perineal bruising (27.3 vs. 5.7%; p = 0.03) and were significantly more likely to require surgery (45.5 vs. 14.2%; p = 0.02). CONCLUSION: Development and implementation of a standardized tool for the differentiation and diagnosis of NAT and creation of a structured electronic medical record note should improve the description and documentation of child abuse cases in a community hospital setting. A retrospective analysis demonstrated that in the absence of such a tool, management of NAT may be inconsistent or incomplete. Perineal injury is an especially ominous red flag finding. PMID- 26809671 TI - Management of Complications and Outcomes After Revisional Bariatric Surgery: 3 Year Experience at a Bariatric Center of Excellence. AB - BACKGROUND: Laparoscopic revisional bariatric surgery (RBS) is increasingly common. A tailored decision-making process is advocated. In this retrospective study, we reviewed the RBS experience of a single center, analyzing perioperative complications to provide insight into management options and midterm outcomes. METHODS: Records from November 2011 to March 2015 were reviewed from prospectively maintained database. Six hundred eighteen patients underwent laparoscopic bariatric procedures; of these, 81 (13.1 %) underwent RBS. Patients with a minimum follow-up of 6 months (n = 77) were evaluated. Fifty-nine underwent revised laparoscopic sleeve gastrectomy, and 18 underwent revised Roux en-Y gastric bypass. Indications for RBS were inadequate weight loss or weight regain in 42 cases (54.5 %) and gastroesophageal reflux disease (GERD), procedure related complications, or technical failure in 35 cases (45.5 %). RESULTS: There were no deaths or conversions to open surgery. After a mean follow-up of 22 months, body mass index (BMI) decreased from 40.9 +/- 6.7 to 31.9 +/- 4.8 kg/m(2), mean % excess weight loss (%EWL) was 58 +/- 24.3 %, and 55.3 % of patients had resolution of comorbidities. Eight major complications (10.4 %) occurred: five leaks and three intra-abdominal hematomas. Non-surgical management succeeded in 50 % of complications. CONCLUSIONS: This study confirms that RBS is challenging; a complication rate of 10 % is expected. Major surgery can be avoided when devoted endoscopists and radiologists are available. Intensive follow-up after complications allows early diagnosis and treatment of unfavorable sequelae. RBS induced a mean %EWL of 58 % at 2 years and resolution of comorbidities in 50 % of cases. However, the durability of these effects remains questionable. PMID- 26809674 TI - Improvement of Lesion Detection by Complete Angular Compound Ultrasonic Elastography. AB - Quasi -: static ultrasound elastography is an emerging diagnostic imaging modality for determining the stiffness of pathologically changed soft tissues, which do not show significant differences in acoustic impedance for B-mode imaging. Although some methods were applied to improve the signal-to-noise ratio (SNRe) and contrast-to-noise ratio (CNRe) of the constructed elastogram, nonuniform strain distribution at the internal boundary of a hard inclusion, even with the uniform displacement on the surface, is an inherent mechanical effect and results in distortion at the detected lesion boundary. To overcome such stress concentrations, a new elastographic modality was proposed, where the elastograms from different angles throughout 360 degrees were compounded. The strain field and subsequent ultrasound images were calculated using the finite element method (FEM) and Field II, respectively, from which the elastograms were constructed. The performance of complete angular compound elastography with varied interval angles, lesion sizes, and ratios of Young's moduli of the lesion to the background was simulated and compared with that of conventional axial strain elastography. It is found that viewing the lesion from only about 10 angles (interval of 36 degrees ) would significantly improve the image quality of elastogram (increasing SNRe by at least 13% and CNRe by at least 5.8 dB), reduce the lesion distortion in the lateral direction, and enhance the sensitivity, resolution, and accuracy of lesion detection. A preliminary phantom study showed similar improvements. Altogether, complete angular compound elastography improves the elastogram quality and reduces the mechanical effects in lesion detection. PMID- 26809675 TI - Identification of factors involved in target RNA-directed microRNA degradation. AB - The mechanism by which micro (mi)RNAs control their target gene expression is now well understood. It is however less clear how the level of miRNAs themselves is regulated. Under specific conditions, abundant and highly complementary target RNA can trigger miRNA degradation by a mechanism involving nucleotide addition and exonucleolytic degradation. One such mechanism has been previously observed to occur naturally during viral infection. To date, the molecular details of this phenomenon are not known. We report here that both the degree of complementarity and the ratio of miRNA/target abundance are crucial for the efficient decay of the small RNA. Using a proteomic approach based on the transfection of biotinylated antimiRNA oligonucleotides, we set to identify the factors involved in target-mediated miRNA degradation. Among the retrieved proteins, we identified members of the RNA-induced silencing complex, but also RNA modifying and degradation enzymes. We further validate and characterize the importance of one of these, the Perlman Syndrome 3'-5' exonuclease DIS3L2. We show that this protein interacts with Argonaute 2 and functionally validate its role in target directed miRNA degradation both by artificial targets and in the context of mouse cytomegalovirus infection. PMID- 26809676 TI - Quantification of read species behavior within whole genome sequencing of cancer genomes for the stratification and visualization of genomic variation. AB - The cancer genome is abnormal genome, and the ability to monitor its sequence had undergone a technological revolution. Yet prognosis and diagnosis remain an expert-based decision, with only limited abilities to provide machine-based decisions. We introduce a heterogeneity-based method for stratifying and visualizing whole-genome sequencing (WGS) reads. This method uses the heterogeneity within WGS reads to markedly reduce the dimensionality of next generation sequencing data; it is available through the tool HiBS (Heterogeneity Based Subclassification) that allows cancer sample classification. We validated HiBS using >200 WGS samples from nine different cancer types from The Cancer Genome Atlas (TCGA). With HiBS, we show progress with two WGS related issues: (i) differentiation between normal (NB) and tumor (TP) samples based solely on the information structure of their WGS data, and (ii) identification of specific regions of chromosomal amplification/deletion and their association with tumor stage. By comparing results to those obtained through available WGS analyses tools, we demonstrate some of the novelties obtained by the approach implemented in HiBS and also show nearly perfect normal/tumor classification, used to identify known and unknown chromosomal aberrations. Finally, the HiBS index has been associated with breast cancer tumor stage. PMID- 26809677 TI - Structures of proline-rich peptides bound to the ribosome reveal a common mechanism of protein synthesis inhibition. AB - With bacterial resistance becoming a serious threat to global public health, antimicrobial peptides (AMPs) have become a promising area of focus in antibiotic research. AMPs are derived from a diverse range of species, from prokaryotes to humans, with a mechanism of action that often involves disruption of the bacterial cell membrane. Proline-rich antimicrobial peptides (PrAMPs) are instead actively transported inside the bacterial cell where they bind and inactivate specific targets. Recently, it was reported that some PrAMPs, such as Bac71 -35, oncocins and apidaecins, bind and inactivate the bacterial ribosome. Here we report the crystal structures of Bac71 -35, Pyrrhocoricin, Metalnikowin and two oncocin derivatives, bound to the Thermus thermophilus 70S ribosome. Each of the PrAMPs blocks the peptide exit tunnel of the ribosome by simultaneously occupying three well characterized antibiotic-binding sites and interferes with the initiation step of translation, thereby revealing a common mechanism of action used by these PrAMPs to inactivate protein synthesis. Our study expands the repertoire of PrAMPs and provides a framework for designing new-generation therapeutics. PMID- 26809680 TI - Future glucose-lowering drugs for type 2 diabetes. AB - The multivariable and progressive natural history of type 2 diabetes limits the effectiveness of available glucose-lowering drugs. Constraints imposed by comorbidities (notably cardiovascular disease and renal impairment) and the need to avoid hypoglycaemia, weight gain, and drug interactions further complicate the treatment process. These challenges have prompted the development of new formulations and delivery methods for existing drugs alongside research into novel pharmacological entities. Advances in incretin-based therapies include a miniature implantable osmotic pump to give continuous delivery of a glucagon-like peptide-1 receptor agonist for 6-12 months and once-weekly tablets of dipeptidyl peptidase-4 inhibitors. Hybrid molecules that combine the properties of selected incretins and other peptides are at early stages of development, and proof of concept has been shown for small non-peptide molecules to activate glucagon-like peptide-1 receptors. Additional sodium-glucose co-transporter inhibitors are progressing in development as well as possible new insulin-releasing biological agents and small-molecule inhibitors of glucagon action. Adiponectin receptor agonists, selective peroxisome proliferator-activated receptor modulators, cellular glucocorticoid inhibitors, and analogues of fibroblast growth factor 21 are being considered as potential new approaches to glucose lowering. Compounds that can enhance insulin receptor and post-receptor signalling cascades or directly promote selected pathways of glucose metabolism have suggested opportunities for future treatments. However, pharmacological interventions that are able to restore normal beta-cell function and beta-cell mass, normalise insulin action, and fully correct glucose homoeostasis are a distant vision. PMID- 26809678 TI - Crystal structures of the BsPif1 helicase reveal that a major movement of the 2B SH3 domain is required for DNA unwinding. AB - Pif1 helicases are ubiquitous members of the SF1B family and are essential for maintaining genome stability. It was speculated that Pif1-specific motifs may fold in specific structures, conferring distinct activities upon it. Here, we report the crystal structures of the Pif1 helicase from Bacteroides spp with and without adenosine triphosphate (ATP) analog/ssDNA. BsPif1 shares structural similarities with RecD2 and Dda helicases but has specific features in the 1B and 2B domains. The highly conserved Pif1 family specific sequence motif interacts with and constraints a putative pin-loop in domain 1B in a precise conformation. More importantly, we found that the 2B domain which contains a specific extended hairpin undergoes a significant rotation and/or movement upon ATP and DNA binding, which is absolutely required for DNA unwinding. We therefore propose a mechanism for DNA unwinding in which the 2B domain plays a predominant role. The fact that the conformational change regulates Pif1 activity may provide insight into the puzzling observation that Pif1 becomes highly processive during break induced replication in association with Poldelta, while the isolated Pif1 has low processivity. PMID- 26809682 TI - Does the preference of peripheral versus central venous access in peripheral blood stem cell collection/yield change stem cell kinetics in autologous stem cell transplantation? AB - Central venous access is often used during apheresis procedure in stem cell collection. The aim of the present study was to evaluate whether central or peripheral venous access has an effect on stem cell yield and the kinetics of the procedure and the product in patients undergoing ASCT after high dose therapy. A total of 327 patients were retrospectively reviewed. The use of peripheral venous access for stem cell yield was significantly more frequent in males compared to females (p = 0.005). Total volume of the product was significantly lower in central venous access group (p = 0.046). As being a less invasive procedure, peripheral venous access can be used for stem cell yield in eligible selected patients. PMID- 26809683 TI - First hematopoietic cell transplantation in Uzbekistan: Progress through education and cooperation. AB - HCT rates are one of the important parameters defining developmental stage of a given country. There is a steady increase in HCT activity on both sides of Atlantic. But in certain parts of the world, HCT activities have yet to begin. Here we report the history of the establishment of the first HCT center and its preliminary activity in Tashkent-Uzbekistan through close cooperation between Turkish Cooperation and Coordination Agency (TIKA) and Uzbekistan Ministry of Health. As of 2014, a total of 10 multiple myeloma patients successfully underwent autologous HCT in Uzbekistan. This encouraging project may be seen as a good example for other developing countries. PMID- 26809685 TI - [Appendicitis in infants. 25 year case series]. PMID- 26809684 TI - DHAP plus filgrastim as an effective peripheral stem cell mobilization regimen for autologous stem-cell transplantation in patients with relapsed/refractory lymphoma: A single center experience. AB - This study aimed to evaluate the efficiency of DHAP regimen plus filgrastim for mobilization of stem cells in patients with recurrent and/or refractory lymphoma. Thirty-four patients who took DHAP as salvage therapy prior to autologous stem cell transplantation were included. After chemotherapies, 2 cycles of DHAP plus filgrastim were administered to the patients. Stem cells from 32 patients (94%) were collected on median 11th day (8-12), and the median collected CD34(+) cell dose was 9.7 * 10(6)/kg (range 3.8-41.6). DHAP plus filgrastim was found to be an effective chemotherapy regimen in mobilizing CD34(+) stem cells into the peripheral. PMID- 26809686 TI - A bioluminescent sensor for highly selective and sensitive detection of human carboxylesterase 1 in complex biological samples. AB - A highly selective and sensitive bioluminescent sensor (DME) for human carboxylesterase 1 (hCE1) has been developed and well characterized. DME could be used for real-time monitoring of hCE1 activities in complex biological samples and for bio-imaging of endogenous hCE1 in living cells. PMID- 26809690 TI - Geographic Variation in Medicare Expenditures, 2003-2012. PMID- 26809691 TI - Integrating the domains of dentistry and research: A perspective from the National Institute of Dental and Craniofacial Research. PMID- 26809688 TI - Induction of DNA double-strand breaks and cellular senescence by human respiratory syncytial virus. AB - Human respiratory syncytial virus (HRSV) accounts for the majority of lower respiratory tract infections during infancy and childhood and is associated with significant morbidity and mortality. HRSV provokes a proliferation arrest and characteristic syncytia in cellular systems such as immortalized epithelial cells. We show here that HRSV induces the expression of DNA damage markers and proliferation arrest such as P-TP53, P-ATM, CDKN1A and gammaH2AFX in cultured cells secondary to the production of mitochondrial reactive oxygen species (ROS). The DNA damage foci contained gammaH2AFX and TP53BP1, indicative of double-strand breaks (DSBs) and could be reversed by antioxidant treatments such as N Acetylcysteine (NAC) or reduced glutathione ethyl ester (GSHee). The damage observed is associated with the accumulation of senescent cells, displaying a canonical senescent phenotype in both mononuclear cells and syncytia. In addition, we show signs of DNA damage and aging such as gammaH2AFX and CDKN2A expression in the respiratory epithelia of infected mice long after viral clearance. Altogether, these results show that HRSV triggers a DNA damage mediated cellular senescence program probably mediated by oxidative stress. The results also suggest that this program might contribute to the physiopathology of the infection, tissue remodeling and aging, and might be associated to long-term consequences of HRSV infections. PMID- 26809692 TI - Practice Location. PMID- 26809693 TI - Electronic Cigarettes. PMID- 26809695 TI - The positive practice. PMID- 26809694 TI - Self-reported temporomandibular joint disorder symptoms, oral health, and quality of life of children in kindergarten through grade 5: Do sex, race, and socioeconomic background matter? AB - BACKGROUND: The authors' objectives were to determine the percentage of children in kindergarten through grade 5 who reported symptoms of temporomandibular joint disorder (TMJD); to assess whether sex, race, and socioeconomic background mattered; and to explore the relationships between TMJD and children's oral health and oral health-related quality of life (OHRQoL). METHODS: The research team conducted face-to-face interviews with 8,302 children in kindergarten through grade 5 (51% female, 49% male; 53% African American, 42% white). They conducted oral health screenings with 7,439 children. RESULTS: Overall, 23.6% of the children reported pain when chewing tough food, and 18.8% reported pain when opening their mouth wide; 23.2% reported hearing a sound (clicking) when opening their mouth wide. Female students were more likely than male students and African American children were more likely than white children to report TMJD symptoms. The prevalence of TMJD symptoms did not correlate with whether the children had a need for oral health care services or whether they had an abscess or carious teeth with pulpal involvement. TMJD symptoms were associated significantly with children's OHRQoL. CONCLUSIONS: Considerable percentages of 4- to 12-year-old children reported TMJD symptoms, with girls and African American children being more likely than their counterparts to be affected. Experiencing TMJD symptoms was associated significantly with poorer OHRQoL. PRACTICAL IMPLICATIONS: Dental practitioners need to be aware that substantial percentages of kindergarten and elementary school-aged children experience TMJD symptoms. Taking a dental history and conducting an oral examination, therefore, should include assessments of the signs and symptoms of TMJD; treatment recommendations should be provided for affected children. PMID- 26809696 TI - Health history questions about sexually transmitted infections: Awkward but necessary. PMID- 26809697 TI - Oral health concerns for older adults. PMID- 26809698 TI - Simple in vitro models can predict pulmonary toxicity of silver nanoparticles. AB - To study the effects of nanomaterials after inhalation, a large number of in vitro lung models have been reported in literature. Although the in vitro models contribute to the reduction of animal studies, insufficient data exists to determine the predictive value of these in vitro models for the in vivo situation. The aim of this study was to determine the correlation between in vitro and in vivo data by comparing the dose metrics of silver nanoparticles in an in vitro lung model of increasing complexity to our previously published in vivo inhalation study. In vivo, the previously published study showed that the alveolar dose expressed as particle surface area is the most suitable dose metric to describe the toxicity of silver nanoparticles after inhalation. The results of the present study show that particle surface area is a suitable dose metric to describe the effects of silver nanoparticles when using a simple monolayer of lung epithelial cells. The dose metric shifted from particle surface area to particle mass when adding an increasing number of macrophages. In addition, a co culture of endothelial cells, epithelial cells and macrophages on a Transwell(r) insert correlated less well to the in vivo results compared to the epithelial monolayer. We conclude that for studying the acute pulmonary toxicity of nanoparticles simple in vitro models using an epithelial monolayer better predict the in vivo response compared to complex co-culture models. PMID- 26809699 TI - Replication Is Good Science. PMID- 26809700 TI - Effect of GO-Fe3O4 and rotating magnetic field on cellular metabolic activity of mammalian cells. AB - The effect of hybrid material-graphene flakes with Fe3O4 nanospheres (GO-Fe3O4), graphene oxide (GO) and magnetite nanospheres (Fe3O4) in rotating magnetic field on mammalian cells metabolism has been studied. Several reports shown that exposure to magnetic field may have influence on cellular membrane permeability. Thus, the aim of presented study was to determine the cellular response of L929 fibroblast cells to nanomaterials and rotating magnetic field for 8-h exposure experiment. The GO had tendency to adsorb proteins, thus cell metabolism was decreased and the effect of that mechanism was enhanced by impact of nanospheres and rotating magnetic field. The highest reduction of cellular metabolism was recorded for WST-1 and NR assays at concentration 100 ug/mL of all tested nanomaterials and magnetic induction value 10.06 mT. The lactate dehydrogenase leakage assay has shown significant changes in membrane permeability. Further studies need to be carried out to precisely determine the mechanism of that process. PMID- 26809701 TI - Evaluation of porous gradient hydroxyapatite/zirconia composites for repair of lumbar vertebra defect in dogs. AB - OBJECTIVE: To evaluate the effects of porous gradient composites with hydroxyapatite/zirconia and autologous iliac in repair of lumbar vertebra body defects in dogs. METHODS: (1) New porous gradient hydroxyapatite/zirconia composites were prepared using foam immersion, gradient compound and high temperature sintering; (2) A total of 18 adult beagle dogs, aged five to eight months and weighted 10-13 kg, were randomly assigned into two subgroups, which were implanted with new porous gradient hydroxyapatite/zirconia composites (subgroup A in 12) or autologous iliac bone (subgroup B in 6); (3) The post operative data were analyzed and compared between the subgroups to repair the vertebral body defect by roentgenoscopy, morphology and biomechanics. RESULTS: The porosity of new porous gradient hydroxyapatite/zirconia composites is at 25 poles per inch, and the size of pores is at between 150 and 300 um. The post operative roentgenoscopy displayed that new-bone formation is increased gradually, and the interface between composites and host-bone becomes became blur, and the new-bone around the composites were integrated into host-bone at 24 weeks postoperatively in subgroup A. As to subgroup B, the resorption and restructure were found at six weeks after the surgery, and the graft-bone and host-bone have been integrated completely without obvious boundary at 24 weeks postoperatively. Histomorphologic study showed that the amount of bone within pores of the porous gradient hydroxyapatite/zirconia composites increased continuously with a prolonged implantation time, and that partial composites were degradated and replaced by new-bone trabeculae. There was no significant difference between subgroups (P > 0.05) in the ultimate compressive strengths. CONCLUSION: New porous gradient hydroxyapatite/zirconia composites can promote the repair of bony defect, and induce bone tissue to ingrow into the pores, which may be applied widely to the treatment of bony defect in the future. PMID- 26809703 TI - How Social Networks Can Affect Infectious Disease Control: An Experience From Northwest Iran. PMID- 26809704 TI - Response to "critically reflecting on Loh's "trends and structural shifts in health tourism"". PMID- 26809705 TI - Dabigatran Plasma Levels in Acute Cerebrovascular Events. AB - BACKGROUND: Oral anticoagulation with dabigatran was shown to be effective for stroke prevention in patients with nonvalvular atrial fibrillation without the need for laboratory monitoring. However, a recent publication based on data of the Randomized Evaluation of Long-Term Anticoagulation Therapy study reported that ischemic stroke and bleeding outcomes are correlated with dabigatran plasma concentration (DPC). DPC was determined at a prespecified time point and correlated with cardiovascular events at any time during follow-up. Because of the known variability of DPC, among others depending on renal function, this approach might compromise data evaluation. We report on dabigatran plasma levels in acute cerebrovascular events. METHODS: Consecutive patients with acute ischemic stroke (AIS) or intracerebral hemorrhage (ICH) while taking dabigatran were retrospectively identified if admission DPC was available. DPC was determined using the diluted thrombin time (Hemoclot (HYPHEN BioMed, Neuville sur Oise, France)). Creatinine clearance (CrCl) was determined by measuring creatinine in plasma and 24-hour urine. RESULTS: Fifteen AIS and 4 ICH patients were included. Median DPC on admission was significantly higher in ICH patients than in AIS patients (135 ng/mL [interquartile range {IQR} 79-218] and 69.1 ng/mL [IQR 20.6-85.0], respectively; P = .035). Increased CrCl (values above published normal range) was correlated with lower median DPC (60 ng/mL [IQR 10-69] versus 100 ng/mL [IQR 79-157] in patients with normal CrCl, P = .01). CONCLUSIONS: Higher DPC was found in ICH patients than in AIS patients in temporal proximity to the event. Both decreased and increased renal functions seem to have an important influence on DPC. PMID- 26809706 TI - Systemic mastocytosis: A cohort study on clinical characteristics of 136 patients in a large tertiary centre. AB - BACKGROUND: Systemic mastocytosis (SM) is a rare heterogeneous disease which is characterized by the aberrant proliferation of mast cells. It can be divided into various subtypes with different phenotypes and prognoses. Here, we report on the clinical characteristics of 136 SM patients. METHODS: A retrospective cohort study was conducted from January 2009 to September 2014 in a large tertiary centre in The Netherlands. We included all patients who fulfilled WHO criteria for SM. Data were collected from electronic patient files. RESULTS: A total of 124 patients had indolent SM (ISM) (91.2%), 7 had aggressive SM (ASM) (5.1%) and 5 had SM with associated hematological non-mast cell lineage disease (SM-AHNMD) (3.7%). There was no progression from ISM to advanced SM subtypes, but 1 patient with ASM developed chronic myelocytic leukemia 2years after diagnosis. The average time to diagnosis for the whole population was 8.1years (range, 0 49years). The most frequent triggers for work-up-skin involvement, anaphylaxis and osteoporosis-were characterized by an interval to diagnosis of 10.9, 2.9 and 7.5years, respectively. A total of 32 patients (23.5%) had a serum tryptase levels below the cutoff value of 20ng/mL at the time of diagnosis, but these patients did not have significant differences in clinical phenotype. CONCLUSIONS: SM comprises a wide spectrum of signs and symptoms and its often atypical presentation can delay the establishment of the diagnosis substantially. Skin involvement, anaphylaxis and unexplained osteoporosis should trigger analysis for mastocytosis. A normal serum tryptase does not exclude the diagnosis of SM. PMID- 26809708 TI - Fostering transition to adulthood for young Australian males: an exploratory study of Men's Sheds' intergenerational mentoring programmes. AB - INTRODUCTION: Men's Sheds are community spaces where socialisation occurs alongside participation in meaningful activities. Shed activities and socialisation make them useful for supporting transition to adulthood of 'at risk' young people through meaningful occupations. Many sheds have implemented intergenerational mentoring programmes. However, many programmes are established on an ad-hoc basis without specific attention to factors that may support effective and sustainable outcomes. We aimed to inform future programmes by exploring different programmes to provide insight into the purpose, design and programme characteristics that are perceived as beneficial for young males. METHOD: Four Sydney-based sheds providing intergenerational mentoring programmes were selected. We interviewed shed coordinators, mentors and mentees to explore their perceptions of programme characteristics that supported mentees' transition to adulthood. Thematic analysis techniques were used to first analyse and understand the unique context of each programme and these were then merged and integrated to identify the most helpful aspects of these mentoring programmes. RESULTS: Mentor attitude towards the mentees, freedom to make independent choices and the nature and perceived usefulness of the project were considered the most significant characteristics of these programmes. CONCLUSION: This was the first known examination of the different characteristics of Men's Sheds intergenerational mentoring programmes. On the basis of our findings, we have made recommendations to help guide the planning and implementation of future programmes. While our findings largely support previous research on mentoring programmes, findings from this study suggest that 'expert skills' may not be as important as mentor attitude to working with the mentees. PMID- 26809709 TI - Subacute thyroiditis following seasonal influenza vaccination. AB - A peritoneal dialysis patient who experienced a repeating attack after a vaccination for influenza while she was being followed and treated succesfully for subacute thyroiditis (SAT) is presented. This case shows SAT as a rare condition following vaccination.. Thus, SAT should be considered as a possible outcome following influenza vaccination and flu-like syndrome. PMID- 26809710 TI - Emergence and evolution of yeast prion and prion-like proteins. AB - BACKGROUND: Prions are transmissible, propagating alternative states of proteins, and are usually made from the fibrillar, beta-sheet-rich assemblies termed amyloid. Prions in the budding yeast Saccharomyces cerevisiae propagate heritable phenotypes, uncover hidden genetic variation, function in large-scale gene regulation, and can act like diseases. Almost all these amyloid prions have asparagine/glutamine-rich (N/Q-rich) domains. Other proteins, that we term here 'prionogenic amyloid formers' (PAFs), have been shown to form amyloid in vivo, and to have N/Q-rich domains that can propagate heritable states in yeast cells. Also, there are >200 other S.cerevisiae proteins with prion-like N/Q-rich sequence composition. Furthermore, human proteins with such N/Q-rich composition have been linked to the pathomechanisms of neurodegenerative amyloid diseases. RESULTS: Here, we exploit the increasing abundance of complete fungal genomes to examine the ancestry of prions/PAFs and other N/Q-rich proteins across the fungal kingdom. We find distinct evolutionary behavior for Q-rich and N-rich prions/PAFs; those of ancient ancestry (outside the budding yeasts, Saccharomycetes) are Q-rich, whereas N-rich cases arose early in Saccharomycetes evolution. This emergence of N-rich prion/PAFs is linked to a large-scale emergence of N-rich proteins during Saccharomycetes evolution, with Saccharomycetes showing a distinctive trend for population sizes of prion-like proteins that sets them apart from all the other fungi. Conversely, some clades, e.g. Eurotiales, have much fewer N/Q-rich proteins, and in some cases likely lose them en masse, perhaps due to greater amyloid intolerance, although they contain relatively more non-N/Q-rich predicted prions. We find that recent mutational tendencies arising during Saccharomycetes evolution (i.e., increased numbers of N residues and a tendency to form more poly-N tracts), contributed to the expansion/development of the prion phenomenon. Variation in these mutational tendencies in Saccharomycetes is correlated with the population sizes of prion like proteins, thus implying that selection pressures on N/Q-rich protein sequences against amyloidogenesis are not generally maintained in budding yeasts. CONCLUSIONS: These results help to delineate further the limits and origins of N/Q-rich prions, and provide insight as a case study of the evolution of compositionally-defined protein domains. PMID- 26809711 TI - Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications. AB - Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD. PMID- 26809713 TI - Two thirds of rheumatology patients wait too long for assessment, audit finds. PMID- 26809712 TI - A Fluorescent Oligothiophene-Bis-Triazine ligand interacts with PrP fibrils and detects SDS-resistant oligomers in human prion diseases. AB - BACKGROUND: Prion diseases are characterized by the accumulation in the central nervous system of an abnormally folded isoform of the prion protein, named PrP(Sc). Aggregation of PrP(Sc) into oligomers and fibrils is critically involved in the pathogenesis of prion diseases. Oligomers are supposed to be the key neurotoxic agents in prion disease, so modulation of prion aggregation pathways with small molecules can be a valuable strategy for studying prion pathogenicity and for developing new diagnostic and therapeutic approaches. We previously identified thienyl pyrimidine compounds that induce SDS-resistant PrP(Sc) (rSDS PrP(Sc)) oligomers in prion-infected samples. RESULTS: Due to the low effective doses of the thienyl pyrimidine hits, we synthesized a quaterthiophene-bis triazine compound, called MR100 to better evaluate their diagnostic and therapeutic potentials. This molecule exhibits a powerful activity inducing rSDS PrP(Sc) oligomers at nanomolar concentrations in prion-infected cells. Fluorescence interaction studies of MR100 with mouse PrP fibrils showed substantial modification of the spectrum, and the interaction was confirmed in vitro by production of rSDS-oligomer species upon incubation of MR100 with fibrils in SDS-PAGE gel. We further explored whether MR100 compound has a potential to be used in the diagnosis of prion diseases. Our results showed that: (i) MR100 can detect rSDS-oligomers in prion-infected brain homogenates of various species, including human samples from CJD patients; (ii) A protocol, called "Rapid Centrifugation Assay" (RCA), was developed based on MR100 property of inducing rSDS-PrP(Sc) oligomers only in prion-infected samples, and avoiding the protease digestion step. RCA allows the detection of both PK-sensitive and PK resistant PrP(Sc) species in rodents samples but also from patients with different CJD forms (sporadic and new variant); (iii) A correlation could be established between the amount of rSDS-PrP(Sc) oligomers revealed by MR100 and the duration of the symptomatic phase of the disease in CJD patients; and (iv) Bioassay experiments showed that MR100 can trap prion infectivity more efficiently than P30 drug. CONCLUSIONS: MR100 is a powerful tool not only for studying the prion aggregation pathways regarding oligomeric and sPrP(Sc) species, but also for developing alternative methods for the detection of prion infected samples. Considering our bioassay results, MR100 is a promising molecule for the development of prion decontamination approaches. PMID- 26809714 TI - Characterization of the biochemical properties of recombinant Xyn10C from a marine bacterium, Saccharophagus degradans 2-40. AB - Endo-1,4-beta-xylanases are mostly classified into glycoside hydrolase (GH) family 10 or 11. In this study, we examined the catalytic functions of a recombinant endo-1,4-beta-xylanase belonging to GH10 (Xyn10C) from a marine bacterium, Saccharophagus degradans 2-40. Optimal activity of this enzyme was evident at 30 degrees C and pH 7.0, but activity remained even at low temperatures, indicating its adaptation to cold. With respect to other xylanases known to be active in cold temperatures, Xyn10C is unique in that it showed maximal activity in the presence of 2 M of NaCl. The action patterns of recombinant Xyn10C on xylans from hardwood and softwood differed in part, but the enzyme hydrolyzed polysaccharidic substrates primarily to xylobiose and xylotriose through xylo-oligosaccharides, releasing a small amount of xylose. The K m and V max values on birchwood xylan were 10.4 mg mL(-1) and 253 umol mg(-1) min(-1), respectively. The efficient catalytic function of Xyn10C on short-length xylo-oligosaccharide chains was similar to the typical function of other known GH10 xylanases. PMID- 26809715 TI - Inoculation effect of thermophilic microorganisms on protease production through solid-state fermentation under non-sterile conditions at lab and bench scale (SSF). AB - The production of protease enzyme was evaluated through the solid state fermentation (SSF) of soy fibre, a waste product that acted as a sole substrate for the fermentation, at a laboratory and bench scale using a 500-mL (batch size 115 g) and 10-L (batch size 2300 g) bioreactors. The objective was to assess the effect of the inoculation of the thermophilic bacteria Thermus sp. on the production of the enzyme when working at laboratory and bench scale under non sterile conditions, since scaling-up and the need of sterilization are the main challenges of SSF, preventing its industrial development. Results revealed that the inoculation led to a substantial increase in the protease obtained on both scales when compared to non-inoculated fermentation. The maximum protease activities increased as a result of the inoculation from 500 to 800 and from 350 to 670 U/g dry matter of soy fibre in the lab and bench scale bioreactors, respectively. Finally, a very good correlation was found between the protease activities obtained and the fermentation most relevant parameters: oxygen uptake rate (R (2) = 0.81) and temperature (R (2) = 0.82). In this work, we have demonstrated that inoculation is effective even under non-sterile conditions at the kg scale and that this strain is able to compete with autochthonous microbiota and increase the protease production to levels higher than those previously reported in literature. PMID- 26809716 TI - Editorial. PMID- 26809717 TI - A Review on the Abundance, Distribution and Eco-Biological Risks of PAHs in the Key Environmental Matrices of South Asia. AB - Polycyclic aromatic hydrocarbons (PAHs) are consistently posing high risks to human/biota in developing countries of South Asia where domestic areas are exposed to biomass burning and commercial/industrial activities. This review article summarized the available data on PAHs occurrence, distribution, potential sources and their possible risks in the key environmental matrices (i.e., Air, Soil/Sediments, Water) from South Asian Region (SAR). Available literature reviewed suggested that PAHs concentration levels were strongly influenced by the monsoonal rainfall system in the region and it has been supported by many studies that higher concentrations were measured during the winter season as compared to summer. Biomass burning (household and brick kilns activities), open burning of solid wastes and industrial and vehicular emissions were categorized as major sources of PAHs in the region. Regional comparison revealed that the contamination levels of PAHs in the water bodies and soil/sediments in SAR remained higher relatively to the reports from other regions of the world. Our findings highlight that there is still a general lack of reliable data, inventories and research studies addressing PAHs related issues in the context of environmental and human health in SAR. There is therefore a critical need to improve the current knowledge base, which should build upon the research experience from other regions which have experienced similar situations in the past. Further research into these issues in South Asia is considered vital to help inform future policies/control strategies as already successfully implemented in other countries. PMID- 26809719 TI - Current status on microRNAs as biomarkers for ovarian cancer. AB - Ovarian cancer (OC) is the most lethal gynecological malignancy in the Western world, and has a very poor prognosis, often due to late diagnosis and emergence of chemotherapy resistance. Therefore, there is an essential need for new diagnostic and prognostic markers that can improve and initiate more personalized treatment, eventually improving survival of the patients. MicroRNAs are small, non-coding RNA molecules, that post-transcriptionally regulate gene expression. Several studies have within the last decade shown that microRNAs are deregulated in OC and have potential as diagnostic and prognostic biomarkers for OC. Recently studies have also focused on microRNAs as predictors of chemotherapy responses and their potential as therapeutic targets. However, many of the published studies are difficult to interpret as a whole due to various methods of analysis. Future focus should be aimed at developing a general standardized analytical method, which can limit differences between studies thus allowing easier comparison across them. In addition, validation of studies in independent series that ideally should be histotype-specific is essential to determine the clinical role of microRNAs in different types of OC. In this review we summarize the current knowledge of microRNAs as potential biomarkers for OC, with focus on their clinical relevance. PMID- 26809718 TI - A pivot mutation impedes reverse evolution across an adaptive landscape for drug resistance in Plasmodium vivax. AB - BACKGROUND: The study of reverse evolution from resistant to susceptible phenotypes can reveal constraints on biological evolution, a topic for which evolutionary theory has relatively few general principles. The public health catastrophe of antimicrobial resistance in malaria has brought these constraints on evolution into a practical realm, with one proposed solution: withdrawing anti malarial medication use in high resistance settings, built on the assumption that reverse evolution occurs readily enough that populations of pathogens may revert to their susceptible states. While past studies have suggested limits to reverse evolution, there have been few attempts to properly dissect its mechanistic constraints. METHODS: Growth rates were determined from empirical data on the growth and resistance from a set of combinatorially complete set of mutants of a resistance protein (dihydrofolate reductase) in Plasmodium vivax, to construct reverse evolution trajectories. The fitness effects of individual mutations were calculated as a function of drug environment, revealing the magnitude of epistatic interactions between mutations and genetic backgrounds. Evolution across the landscape was simulated in two settings: starting from the population fixed for the quadruple mutant, and from a polymorphic population evenly distributed between double mutants. RESULTS: A single mutation of large effect (S117N) serves as a pivot point for evolution to high resistance regions of the landscape. Through epistatic interactions with other mutations, this pivot creates an epistatic ratchet against reverse evolution towards the wild type ancestor, even in environments where the wild type is the most fit of all genotypes. This pivot mutation underlies the directional bias in evolution across the landscape, where evolution towards the ancestor is precluded across all examined drug concentrations from various starting points in the landscape. CONCLUSIONS: The presence of pivot mutations can dictate dynamics of evolution across adaptive landscape through epistatic interactions within a protein, leaving a population trapped on local fitness peaks in an adaptive landscape, unable to locate ancestral genotypes. This irreversibility suggests that the structure of an adaptive landscape for a resistance protein should be understood before considering resistance management strategies. This proposed mechanism for constraints on reverse evolution corroborates evidence from the field indicating that phenotypic reversal often occurs via compensatory mutation at sites independent of those associated with the forward evolution of resistance. Because of this, molecular methods that identify resistance patterns via single SNPs in resistance-associated markers might be missing signals for resistance and compensatory mutation throughout the genome. In these settings, whole genome sequencing efforts should be used to identify resistance patterns, and will likely reveal a more complicated genomic signature for resistance and susceptibility, especially in settings where anti-malarial medications have been used intermittently. Lastly, the findings suggest that, given their role in dictating the dynamics of evolution across the landscape, pivot mutations might serve as future targets for therapy. PMID- 26809721 TI - Characterization and novel analyses of acute stress response patterns in a population-based cohort of young adults: influence of gender, smoking, and BMI. AB - Dysregulation of the biological stress response system has been implicated in the development of psychological, metabolic, and cardiovascular disease. Whilst changes in stress response are often quantified as an increase or decrease in cortisol levels, three different patterns of stress response have been reported in the literature for the Trier Social Stress Test (TSST) (reactive-responders (RR), anticipatory-responders (AR) and non-responders (NR)). However, these have never been systematically analyzed in a large population-based cohort. The aims of this study were to examine factors that contribute to TSST variation (gender, oral contraceptive use, menstrual cycle phase, smoking, and BMI) using traditional methods and novel analyses of stress response patterns. We analyzed the acute stress response of 798, 18-year-old participants from a community-based cohort using the TSST. Plasma adrenocorticotrophic hormone, plasma cortisol, and salivary cortisol levels were quantified. RR, AR, and NR patterns comprised 56.6%, 26.2%, and 17.2% of the cohort, respectively. Smokers were more likely to be NR than (RR or AR; adjusted, p < 0.05). Overweight and obese subjects were less likely to be NR than the other patterns (adjusted, p < 0.05). Males were more likely to be RR than NR (adjusted, p = 0.05). In addition, we present a novel AUC measure (AUCR), for use when the TSST baseline concentration is higher than later time points. These results show that in a young adult cohort, stress response patterns, in addition to other parameters vary with gender, smoking, and BMI. The distribution of these patterns has the potential to vary with adult health and disease and may represent a biomarker for future investigation. PMID- 26809723 TI - Definitive airway management in emergency department patients with a King laryngeal tubeTM in place: a simple and safe approach. PMID- 26809724 TI - In reply: Definitive airway management in emergency department patients with a King laryngeal tubeTM in place: a simple and safe approach. PMID- 26809725 TI - A Vision of Reading. AB - Different fields of research within the cognitive sciences have investigated basic processes in reading, but progress has been hampered by limited cross fertilization. We propose a theoretical framework aimed at facilitating integration of findings obtained via these different approaches with respect to the impact of visual factors on reading. We describe a specialized system for parallel letter processing that assigns letter identities to different locations along the horizontal meridian within the limits imposed by visual acuity and crowding. Spatial attention is used to set up this system during reading development, and difficulty in doing so has repercussions in terms of efficient translation of the orthographic code into its phonological counterpart, and fast access to semantics from print. PMID- 26809726 TI - Caring About Dostoyevsky: The Untapped Potential of Studying Literature. AB - Should cognitive scientists and neuroscientists care about Dostoyevsky? Engaging with fiction is a natural and rich behavior, providing a unique window onto the mind and brain, particularly for mental simulation, emotion, empathy, and immersion. With advances in analysis techniques, it is time that cognitive scientists and neuroscientists embrace literature and fiction. PMID- 26809730 TI - Characterization of deoxyribozymes with site-specific oxidative cleavage activity against DNA obtained by in vitro selection. AB - We identified a new class of deoxyribozymes named A-2 and A-3 by in vitro selection which required both Cu(2+) and Mn(2+) as cofactors that selectively and rapidly cleave the DNA substrate. Studies confirmed that they cleaved via a mechanistic pathway involving the formation of hydrogen peroxide as the reactive species. The kinetics, secondary structures and sequence tolerance of the new class of the deoxyribozymes A-2 and A-3 were reported. PMID- 26809732 TI - A rare cause of GI bleeding in a patient with cutaneous vascular malformations. PMID- 26809734 TI - High proportions of obstetric referrals in Addis Ababa: the case of term premature rupture of membranes. AB - BACKGROUND: The Public Health Centers (HCs) provide basic obstetric and neonatal care to about 80% of the eligible population in Addis Ababa. Hospitals provide comprehensive services and are referral centers for complications that cannot be managed at the HCs. This study assessed the proportion of obstetric referrals in general and referrals due to premature rupture of membranes (PROM) at term in particular, from the HCs in Addis Ababa and explored its appropriateness and management in hospitals. METHODS: The study used a sequential explanatory mixed methods design. Routine retrospective data were collected from ten randomly selected HCs in 2012. Key informant interviews were conducted using a guide developed following a preliminary analysis of the quantitative data. Ten head midwives, one from each health center participated in the interviews. RESULTS: Of the 9340 mothers who sought skilled birth care in the ten HCs in 2012, 2820 (30.3%) were diagnosed with obstetric complications and referred to hospital. Term PROM accounted for 557 (19.7%) of the referrals and it was widely varied across the HCs. Fifteen (7.8%) mothers who were referred for PROM, had intact membranes upon hospital examinations. Forty-two (77.8%) of the referred mothers who had spontaneous labour and delivery could have been misclassified as not having labour upon referral. In the interviews, variations in diagnosing and managing term PROM were identified as themes. Three HCs relayed solely on mothers' self reports of amniotic fluid leakage to diagnose, two HCs did complementary speculum/vaginal examination, three HCs monitored sign of labour on top of confirming the leakage. Regarding management, two HCs practiced expectant management, three referred mothers after 30 min of observation while others issued referral right away. All providers reported the lack of clinical guidelines for most common obstetric problems in their HC. CONCLUSIONS: The study reported large proportion of obstetric referrals in general and PROM referrals in particular as well as variations in diagnosing and managing term PROM. These could largely be attributed to lack of clinical guidelines for most common obstetric complications at the HCs and competency gap among providers. Addressing the identified gaps and strengthening the primary care settings could contribute to improved quality of obstetric care and outcomes. PMID- 26809737 TI - Effects of the rotation angle on surface plasmon coupling of nanoprisms. AB - We studied the effects of relative orientation of bowtie nanostructures on the plasmon resonance both experimentally and theoretically in this work. Specifically, we fabricated gold bowtie nanoantennas with rotated nanoprisms, measured the near-field and the far-field resonance behaviors using Raman spectroscopy and scattering microspectroscopy, and simulated the effects of the rotation angle on the localized surface plasmonic resonance using finite difference time-domain simulations. In addition to the widely-discussed dipolar resonance in regular bowtie nanostructures, defined as tip-mode resonance in the present study, the excitations of edge-mode resonance were discovered under certain rotation angles of nanoprisms. Because of the resonances of different modes at different wavelengths, two different incident laser sources were used to measure the Raman spectra to provide evidence for the evolution of different resonance modes. Also, both the tip-mode and edge-mode resonances were verified by the simulated charge density distribution and their trends were discussed. Based on the discovered trend, a plasmon protractor was created with a near exponential decay relationship between the relative resonance wavelength shift and cosine of the rotation angle. A plasmon hybridization model was also proposed for rotated bowties to explain the coupling between nanoprisms during rotation. PMID- 26809736 TI - Killer-cell Immunoglobulin-like Receptor (KIR) gene profiles modify HIV disease course, not HIV acquisition in South African women. AB - BACKGROUND: Killer-cell Immunoglobulin-like Receptors (KIR) interact with Human Leukocyte Antigen (HLA) to modify natural killer- and T-cell function. KIR are implicated in HIV acquisition by small studies that have not been widely replicated. A role for KIR in HIV disease progression is more widely replicated and supported by functional studies. METHODS: To assess the role of KIR and KIR ligands in HIV acquisition and disease course, we studied at-risk women in South Africa between 2004-2010. Logistic regression was used for nested case-control analysis of 154 women who acquired vs. 155 who did not acquire HIV, despite high exposure. Linear mixed-effects models were used for cohort analysis of 139 women followed prospectively for a median of 54 months (IQR 31-69) until 2014. RESULTS: Neither KIR repertoires nor HLA alleles were associated with HIV acquisition. However, KIR haplotype BB was associated with lower viral loads (-0.44 log10 copies/ml; SE = 0.18; p = 0.03) and higher CD4+ T-cell counts (+80 cells/MUl; SE = 42; p = 0.04). This was largely explained by the protective effect of KIR2DL2/KIR2DS2 on the B haplotype and reciprocal detrimental effect of KIR2DL3 on the A haplotype. CONCLUSIONS: Although neither KIR nor HLA appear to have a role in HIV acquisition, our data are consistent with involvement of KIR2DL2 in HIV control. Additional studies to replicate these findings are indicated. PMID- 26809738 TI - Femoral geometry, bone mineral density, and the risk of hip fracture in premenopausal women: a case control study. AB - BACKGROUND: The purpose of this study was to determine the relationships among hip geometry, bone mineral density, and the risk of hip fracture in premenopausal women. METHODS: The participants in this case-control study were 16 premenopausal women with minimal-trauma hip fractures (fracture group) and 80 age-and BMI adjusted controls. Subjects underwent dual-energy X-ray absorptiometry (DXA) to assess BMD at the proximal femur and to obtain DXA-derived hip geometry measurements. RESULTS: The fracture group had a lower mean femoral neck and total hip BMD than the control group (0.721 +/- 0.123 vs. 0.899 +/- 0.115, p <0.001 for the femoral neck BMD and 0.724 +/- 0.120 vs. 0.923 +/- 0.116, p <0.001 for the total hip BMD). In addition, participants in the fracture group had a longer hip axis length (HAL; p = 0.007), narrower neck shaft angle (NSA; p = 0.008), smaller cross sectional area (CSA; p < 0.001) and higher cross sectional moment of inertia (CSMI; p = 0.004) than those in control group. After adjusting for BMD, the fracture group still had a significantly longer mean HAL (p = 0.020) and narrower NSA (p = 0.006) than the control group. CONCLUSIONS: BMD is an important predictor of hip fracture in premenopausal women. Furthermore, HAL and NSA are BMD-independent predictors of hip fracture in premenopausal women. Hip geometry may be clinically useful for identification of premenopausal women for whom active fracture prevention should be considered. PMID- 26809739 TI - Erratum to: Primary glioblastoma multiforme tumors and recurrence: comparative analysis of the danger signals HMGB1, HSP70, and calreticulin. PMID- 26809740 TI - An integrative review exploring decision-making factors influencing mental health nurses in the use of restraint. AB - WHAT IS KNOWN ON THE SUBJECT?: There is emerging evidence highlighting the counter therapeutic impact of the use of restraint and promoting the minimization of this practice in mental health care. Mental health nurses are often the professional group using restraint and understanding factors influencing their decision-making becomes critical. To date, there are no other published papers that have undertaken a similar broad search to review this topic. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Eight emerging themes are identified as factors influencing mental health nurses decisions-making in the use of restraint. The themes are: 'safety for all', 'restraint as a necessary intervention', 'restraint as a last resort', 'role conflict', 'maintaining control', 'staff composition', 'knowledge and perception of patient behaviours', and 'psychological impact'. 'Last resort' appears to be the mantra of acceptable restraint use, although, to date, there are no studies that specifically consider what this concept actually is. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: These findings should be considered in the evaluation of the use of restraint in mental health settings and appropriate strategies placed to support shifting towards restraint minimization. As the concept of 'last resort' is mentioned in many policies and guidelines internationally with no published understanding of what this means, research should prioritize this as a critical next step in restraint minimization efforts. INTRODUCTION: While mechanical and manual restraint as an institutional method of control within mental health settings may be perceived to seem necessary at times, there is emergent literature highlighting the potential counter therapeutic impact of this practice for patients as well as staff. Nurses are the professional group who are most likely to use mechanical and manual restraint methods within mental health settings. In-depth insights to understand what factors influence nurses' decision-making related to restraint use are therefore warranted. AIM: To explore what influences mental health nurses' decision-making in the use of restraint. METHOD: An integrative review using Cooper's framework was undertaken. RESULTS: Eight emerging themes were identified: 'safety for all', 'restraint as a necessary intervention', 'restraint as a last resort', 'role conflict', 'maintaining control', 'staff composition', 'knowledge and perception of patient behaviours', and 'psychological impact'. These themes highlight how mental health nurses' decision-making is influenced by ethical and safety responsibilities, as well as, interpersonal and staff-related factors. CONCLUSION: Research to further understand the experience and actualization of 'last resort' in the use of restraint and to provide strategies to prevent restraint use in mental health settings are needed. PMID- 26809742 TI - Studies of human polyomaviruses, with HPyV7, BKPyV, and JCPyV present in urine of allogeneic hematopoietic stem cell transplanted patients with or without hemorrhagic cystitis. AB - BACKGROUND: BK polyomavirus (BKPyV) can cause hemorrhagic cystitis (HC) in allogeneic hematopoietic stem cell transplant (allo-HSCT) patients and polyomavirus-associated nephritis in renal transplant patients, while JC polyomavirus (JCPyV) can generate progressive multifocal leukoencephalopathy in immunocompromised individuals. Since 2007, additional human polyomaviruses (HPyVs) have been identified. In this study, we examined the urines of allo-HSCT patients for possible presence of polyomaviruses BKPyV, JCPyV, KIPyV, WUPyV, MCPyV, HPyV6, HPyV7, TSPyV, HPyV9, and HPyV10 (MWPyV). METHODS: A total of 185 urinary samples obtained 2002-2007 from 105 allo-HSCT patients, 32/105 with HC, were tested for the above-listed HPyVs by a bead-based multiplex assay. Of these, 142 urine samples had previously been tested for BKPyV and JCPyV by nested polymerase chain reaction (PCR). RESULTS: Aside from BKPyV and JCPyV, which dominated, HPyV7 was detected in 5 BKPyV-positive urinary samples from 1 patient. The multiplex assay was more sensitive and specific than the nested PCR. BKPyV and/or JCPyV were found in all but 1 of the previously BKPyV- or JCPyV-positive samples, although 6 previously BKPyV-positive cases were now JCPyV-positive or the reverse. Furthermore, 18/79 previously negative samples were found to be BKPyV and/or JCPyV positive, and a total of 21 double infections were found. Lastly, in 1/29 HC patients, only JCPyV was detected. CONCLUSION: HPyV7 was found for the first time in urine of an allo-HSCT patient, and BKPyV and JCPyV were more commonly found in urine samples using the bead-based assay compared to testing by nested PCR. Finally, only JCPyV was detected in the urine of 1 HC patient. PMID- 26809744 TI - Assessment of heavy metal pollution in surface soils and plant material in the post-industrial city of Katowice, Poland. AB - This investigation was undertaken to assess the level of environment pollution by biological monitoring. The leaves and bark of popular ornamental trees Acer pseudoplatanus L. and Acer platanoides L. and soil from the sampling sites were used to perform heavy metals pollution monitoring in urban areas with different pollution sources, as well to investigate the suitability of the leaves and bark as bioindicators of Pb, Zn, Cd and Cu pollution. Plant samples were collected at nine locations classified into three pollution groups based on metal content in the soils. The chosen pollution indices were used to assess the level of contamination according to background values. Soils in the Katowice area are found to be relatively heavily contaminated with Pb, Zn and Cd. Both of the maple tree species did not statistically differ in terms of the investigated elements' concentration in leaves or bark. Only bark samples reflected the pollution level, showing differences between the sampling points, and therefore are recommended for biomonitoring purposes. PMID- 26809745 TI - Timing of Initiation of Maintenance Dialysis: A Qualitative Analysis of the Electronic Medical Records of a National Cohort of Patients From the Department of Veterans Affairs. AB - IMPORTANCE: There is often considerable uncertainty about the optimal time to initiate maintenance dialysis in individual patients and little medical evidence to guide this decision. OBJECTIVE: To gain a better understanding of the factors influencing the timing of initiation of dialysis in clinical practice. DESIGN, SETTING, AND PARTICIPANTS: A qualitative analysis was conducted using the electronic medical records from the Department of Veterans Affairs (VA) of a national random sample of 1691 patients for whom the decision to initiate maintenance dialysis occurred in the VA between January 1, 2000, and December 31, 2009. Data analysis took place from June 1 to November 30, 2014. MAIN OUTCOMES AND MEASURES: Central themes related to the timing of initiation of dialysis as documented in patients' electronic medical records. RESULTS: Of the 1691 patients, 1264 (74.7%) initiated dialysis as inpatients and 1228 (72.6%) initiated dialysis with a hemodialysis catheter. Cohort members met with a nephrologist during an outpatient clinic visit a median of 3 times (interquartile range, 0-6) in the year prior to initiation of dialysis. The mean (SD) estimated glomerular filtration rate at the time of initiation for cohort members was 10.4 (5.7) mL/min/1.73 m(2). The timing of initiation of dialysis reflected the complex interplay of at least 3 interrelated and dynamic processes. The first was physician practices, which ranged from practices intended to prepare patients for dialysis to those intended to forestall the need for dialysis by managing the signs and symptoms of uremia with medical interventions. The second process was sources of momentum. Initiation of dialysis was often precipitated by clinical events involving acute illness or medical procedures. In these settings, the imperative to treat often seemed to override patient choice. The third process was patient-physician dynamics. Interactions between patients and physicians were sometimes adversarial, and physician recommendations to initiate dialysis sometimes seemed to conflict with patient priorities. CONCLUSIONS AND RELEVANCE: The initiation of maintenance dialysis reflects the care practices of individual physicians, sources of momentum for initiation of dialysis, interactions between patients and physicians, and the complex interplay of these dynamic processes over time. Our findings suggest opportunities to improve communication between patients and physicians and to better align these processes with patients' values, goals, and preferences. PMID- 26809747 TI - Immunoregulatory Forkhead Box Protein p3-Positive Lymphocytes Are Associated with Overall Survival in Patients with Pancreatic Neuroendocrine Tumors. AB - BACKGROUND: Forkhead box protein p3-positive (FoxP3(+)) regulatory T cells (Tregs) suppress host T-cell-mediated immune responses, limit surveillance against cancers, and have been associated with a poor prognosis. STUDY DESIGN: This study aims to identify the prognostic significance of FoxP3(+) Tregs in pancreatic neuroendocrine tumors (PNETs). Patients diagnosed with PNETs between 1992 and 2014 (n = 101) were included in this retrospective analysis. Clinical data, histopathology, and expression of FoxP3(+) Tregs and Ki-67 by immunohistochemistry were assessed. The association of these factors with survival was tested by log-rank test and in additional multivariable analysis. RESULTS: A total of 101 patients were included in this study. Mean age was 58.0 years (range 18 to 87 years) and median tumor size was 25 mm (range 8 to 160 mm). The degree of infiltration of tumor by FoxP3(+) Tregs was graded as 0 (n = 75), 1 (n = 15), or 2 (n = 11). Median follow-up was 50 months (interquartile range 123 months; Q1 = 20 months and Q3 = 123 months). In univariate analyses, patient age older than 57 years, TNM stage III or IV, tumor size >25 mm, Ki-67 labeling index >20, and a high number of FoxP3(+) tumor-infiltrating lymphocytes were significantly associated with poorer overall survival. In multivariable analyses, FoxP3(+) expression score of 2 (hazard ratio = 6.9; 95% CI 1.4-34.4) was the only statistically significant predictor for overall mortality. CONCLUSIONS: FoxP3(+) Treg expression is an independent prognostic factor in patients with PNETs, associated with statistically significant shorter overall survival. There is a role for additional research into the immune-mediated role of FoxP3(+) Tregs in PNETs. PMID- 26809748 TI - Restating Surgical Risk: From Patient to Population. AB - BACKGROUND: Recent federal legislation driving transition from fee-for-service to alternative methods of payment makes risk recognition essential for determination of appropriate payment systems. Because negotiations will include bundled population cohorts, we compared risk and results of an urban safety net teaching hospital's surgical population with state and national cohorts. STUDY DESIGN: Deidentified summary data for 2013 and 2014 were analyzed to compare the safety net teaching hospital with a statewide collaborative and a national cohort from similar academic centers. Incidence of preoperative risk factors were compared, identifying those that were >50% higher than both state and national experiences. These were compared for change in incidence between years. Outcomes were evaluated by 30-day mortality, readmissions, return to operating room, length of stay, and adverse events incidence. RESULTS: For both years, incidence of smoking, ventilator dependence, and CHF within 30 days was >50% higher than in the state and national cohorts. In 2014, septic shock was added to this, along with increased diabetes (14.3% to 19.8%), CHF (1.9% to 2.8%), and hypertension (39.9% to 52.5%). Despite these changes, 30-day mortality, return to operating room, length of stay, and readmissions were within +/-5% of state and national results. Unplanned intubation, ventilation longer than 48 hours, and acute renal failure were 10th decile outliers. Median and interquartile range for length of stay were similar for all 3 populations across both years. CONCLUSIONS: The incidence of comorbid conditions defines greater risk in this safety net teaching hospital population. Increased smoking-related pathology reflects local population disease burden, and increased ventilator support defines additional cost for this care. As disease-, procedure-, or population-based payment alternatives evolve, risk recognition, reduction, and resolution will be essential for determination of cost-efficient, optimal, surgical outcomes. PMID- 26809749 TI - High Body Mass Index as a Risk Factor for Hospitalization Due to Influenza: A Case-Control Study. AB - INTRODUCTION: Obesity has emerged as a significant independent predictor of severity in pandemic influenzaA (H1N1)pdm09. The aim of this study was to investigate the association between body mass index (BMI) and the risk of hospitalization due to influenza. METHODS: Hospitalized patients (n=755) with laboratory-confirmed influenza were individually matched by age, admission/visit date, and province with an outpatient (n=783) with laboratory-confirmed influenza and an outpatient control (n=950). We compared the BMI using conditional logistic regression adjusted for potential confounding factors (aOR). The population attributable fraction (PAF) was calculated. RESULTS: A higher BMI was associated with an increased risk of hospitalization compared to both outpatient cases (aOR=1.11; 95%CI: 1.07-1.16) and outpatient controls (aOR=1.04; 95%CI: 1.01 1.07). Compared with normal weight, obesity type I, obesity type II and obesity type III was associated with a greater likelihood of hospitalization compared with outpatient cases (aOR=1.85, 95%CI: 1.05-3.26; aOR=5.24, 95%CI: 1.94-14.15 and aOR=44.38, 95%CI: 4.47-440.5). Compared with normal weight, obesity type II and obesity type III was associated with a greater likelihood of hospitalization compared with outpatient controls (aOR=4.37, 95%CI: 1.79-10.69 and aOR=4.95, 95%CI: 1.45-16.87). In persons without influenza vaccination, all categories of BMI>=30kg/m(2) were associated with a greater likelihood of hospitalization compared with normal weight in both outpatient cases and outpatient controls. The PAF of hospitalization by influenza due to BMI ranged from 21.9% to 8.5%; in the case of unvaccinated against influenza between 20.5% to 16.9%. CONCLUSION: A high BMI is associated with an increased risk of hospitalization due to influenza. High percentage of hospital admissions are attributable to their BMI, especially in non vaccinated. PMID- 26809751 TI - Bevacizumab, temozolomide, and radiotherapy for newly diagnosed glioblastoma: comprehensive safety results during and after first-line therapy. AB - BACKGROUND: The proposed use of bevacizumab with radiotherapy/temozolomide for newly diagnosed glioblastoma raised potential safety concerns. Bevacizumab has been linked with stroke, bleeding events, and wound-healing complications in other tumor types; these events are of particular concern for glioblastoma (highly vascular tumors that are usually resected). Published data on the interaction of bevacizumab with radiotherapy/temozolomide are also limited. We report safety data from a phase III randomized trial (Avastin in Glioblastoma), focusing on these considerations. METHODS: Eligible patients received: radiotherapy and temozolomide plus bevacizumab/placebo, 6 cycles; a 4-week treatment break; temozolomide plus bevacizumab/placebo, 6 cycles; and bevacizumab/placebo until progression. Data on adverse events (AEs) were collected throughout. RESULTS: Bevacizumab-treated patients (n = 461) had a longer median safety follow-up time (12.3 vs 8.5 mo), and a higher proportion completed 6 cycles of maintenance temozolomide (64.6% vs 36.9%) versus placebo (n = 450). The incidences of relevant AEs (bevacizumab vs placebo, respectively) were: arterial thromboembolic events (5.9% vs 1.6%); cerebral hemorrhage (3.3% vs 2.0%); wound-healing complications (6.9% vs 4.7%); thrombocytopenia (34.1% vs 27.3%); radiotherapy-associated skin injury (8.2% vs 9.3%); alopecia (39.0% vs 36.0%); gastrointestinal perforation (including gastrointestinal abscesses and fistulae, 1.7% vs 0.4%); and radiotherapy-associated injury (0.4% vs 0.0%). Overall, 15.8% and 23.8% of bevacizumab- and placebo-treated patients had surgery (including biopsy) after progression. Within 30 days of postprogression surgery, AE incidence was 10.9% (bevacizumab) and 23.4% (placebo). CONCLUSION: The safety profile was consistent with that expected from radiotherapy/temozolomide plus bevacizumab. The increased AE incidence with bevacizumab did not impact patients' ability to receive standard-of-care treatment or to undergo further surgery. PMID- 26809753 TI - Perception, Attitude, and Knowledge Regarding Antimicrobial Resistance, Appropriate Antimicrobial Use, and Infection Control Among Future Medical Practitioners: A Multicenter Study. AB - A questionnaire-based study was conducted among final-year Thai medical students. The problem of antimicrobial resistance is well recognized, but their knowledge of antimicrobial resistance, appropriate antimicrobial use, and infection control was substantially limited. Only half of these students recognized existence of an antimicrobial stewardship program or infection control unit in their hospitals. PMID- 26809754 TI - Laparoscopic, hybrid, and totally robotic Roux-en-Y gastric bypass. AB - The laparoscopic approach to Roux-en-Y gastric bypass (RYGB) is a highly regarded and frequently used bariatric procedure. We review our experience with robotic approaches to RYGB. We hypothesized that the robotic approach is safe and may produce similar outcomes to previously reported laparoscopic surgery. We conducted our study at the University Hospital, USA. Data regarding RYGB procedures performed in 2006-2013 were retrospectively reviewed from a prospectively maintained, dedicated database. Procedures were categorized into three groups: laparoscopic, hybrid robotic (HR), and total robotic (TR). Patient characteristics, operative variables, and postoperative short- and long-term outcomes were compared between groups and to recently published larger laparoscopic series. Our study included 192 RYGB consecutive patients who underwent laparoscopic, HR, or TR surgery. Mean patient age, preoperative body mass index, and preoperative weight were 40.4 +/- 9.3 years (range 22-64), 46. 2 +/- 5.9 kg/m(2) (range 35-64), and 130. 3 +/- 22.1 kg (range 76.7-193.4) respectively. Ninety-two patients (47.9 %) had undergone previous abdominal surgery. Mean operative time, estimated blood loss, and length of stay were 223.4 +/- 39.2 min (range 130-338), 21.9 +/- 18.8 mL (range 5-10), and 2.6 +/- 1.1 days (range 2-15), respectively. There were 248 concomitant procedures such as upper endoscopy, cholecystectomy, etc., 7 revisional surgeries, and 2 conversions to open surgery. Intraoperative complications included one liver laceration and one bowel injury. There were two cases each of bowel obstruction, transfusions, and deep vein thrombosis/pulmonary embolus, but no deaths or anastomotic leaks. Early experience with TR approach for RYGB is safe, with similar outcomes to the laparoscopic approach. PMID- 26809755 TI - Evaluation of conventional laparoscopic versus robot-assisted laparoscopic redo hiatal hernia and antireflux surgery: a cohort study. AB - Surgery for refractory gastroesophageal reflux disease (GERD) and hiatal hernia leads to recurrence or persisting dysphagia in a minority of patients. Redo antireflux surgery in GERD and hiatal hernia is known for higher morbidity and mortality. This study aims to evaluate conventional versus robot-assisted laparoscopic redo antireflux surgery, with the objective to detect possible advantages for the robot-assisted approach. A single institute cohort of 75 patients who underwent either conventional laparoscopic or robot-assisted laparoscopic redo surgery for recurrent GERD or severe dysphagia between 2008 and 2013 were included in the study. Baseline characteristics, symptoms, medical history, procedural data, hospital stay, complications and outcome were prospectively gathered. The main indications for redo surgery were dysphagia, pyrosis or a combination of both in combination with a proven anatomic abnormality. The mean time to redo surgery was 1.9 and 2.0 years after primary surgery for the conventional and robot-assisted groups, respectively. The number of conversions was lower in the robot-assisted group compared to conventional laparoscopy (1/45 vs. 5/30, p = 0.035) despite a higher proportion of patients with previous surgery by laparotomy (9/45 vs. 1/30, p = 0.038). Median hospital stay was reduced by 1 day (3 vs. 4, p = 0.042). There were no differences in mortality, complications or outcome. Robotic support, when available, can be regarded beneficial in redo surgery for GERD and hiatal hernia. Results of this observational study suggest technical feasibility for minimal-invasive robot assisted redo surgery after open primary antireflux surgery, a reduced number of conversions and shorter hospital stay. PMID- 26809756 TI - [Mutation in RET gene: Prophylactic thyroidectomy and postoperative follow-up]. PMID- 26809757 TI - [The binomial symptom index for the evaluation of temporal association between cardiorespiratory symptoms and gastroesophageal reflux in neonates]. AB - INTRODUCTION: The evaluation of symptom association between gastroesophageal reflux and cardiorespiratory events in preterm infants remains unclear. This paper describes a conservative approach to decision-making of anti-reflux surgery through symptom association analysis. METHODS: Forty-three neonates with potentially reflux-related cardiorespiratory symptoms underwent synchronized esophageal impedance-pH and cardiorespiratory monitoring. Three indices were considered to evaluate symptom association, the symptom index (SI), the symptom sensitivity index (SSI) and the symptom association probability (SAP). A conservative strategy was adopted regarding the decision of anti-reflux surgery, and therefore, patients were scheduled for laparoscopic Nissen fundoplication if the three indices showed a positive assessment of symptom association. Retrospectively, these indices and the binomial symptom index (BSI) were contrasted against the decision of anti-reflux surgery using different windows of association. RESULTS: Thirteen patients showed positive symptom association but only two underwent anti-reflux surgery. The SI and the SSI showed an increasing trend with the width of the window of association. The SAP was affected randomly by slightly altering the windowing parameters. The BSI showed the best performance with the two-minute window (kappa =0.78) CONCLUSIONS: The pathology under study is known to improve with maturity. However, the severity of cardiorespiratory symptoms may threaten the neonate's life and therefore, in some occasions, invasive treatments must be considered to protect life. The BSI provides a good prediction of a combination of positive SI, SSI and SAP, which may improve clinical decisions. However, further clinical studies are required to prove the BSI as an optimal predictor of clinical outcomes. PMID- 26809759 TI - A review of predictive coding algorithms. AB - Predictive coding is a leading theory of how the brain performs probabilistic inference. However, there are a number of distinct algorithms which are described by the term "predictive coding". This article provides a concise review of these different predictive coding algorithms, highlighting their similarities and differences. Five algorithms are covered: linear predictive coding which has a long and influential history in the signal processing literature; the first neuroscience-related application of predictive coding to explaining the function of the retina; and three versions of predictive coding that have been proposed to model cortical function. While all these algorithms aim to fit a generative model to sensory data, they differ in the type of generative model they employ, in the process used to optimise the fit between the model and sensory data, and in the way that they are related to neurobiology. PMID- 26809765 TI - Intraoperative Anemia and Single Red Blood Cell Transfusion During Cardiac Surgery: An Assessment of Postoperative Outcome Including Patients Refusing Blood Transfusion. AB - OBJECTIVES: Increasing evidence suggests benefits from restrictive red blood cell transfusion (RBC) thresholds in major surgery and critically ill patients. However, these benefits are not obvious in cardiac surgery patients with intraoperative anemia. The authors examined the association between uncorrected hemoglobin (Hb) levels and selected postoperative outcomes as well as the effects of RBCs. DESIGN: Cohort study with prospectively collected data from a cardiac surgery registry. SETTING: A major cardiac surgical hospital within the Netherlands, which is also a referral center for Jehovah's Witnesses. PARTICIPANTS: Patients (23,860) undergoing cardiac surgery between 1997 and 2013. INTERVENTIONS: Comparisons were done in patients with intraoperative nadir Hb<8 g/dL and/or an Hb decrease >= 50%. Comparison (A) between Jehovah's Witnesses (Witnesses) and matched non-Jehovah's Witnesses (non-Witnesses) transfused with 1 unit of RBC, and comparison (B) between patients given 1 unit of RBC intraoperatively versus matched non-transfused patients. MEASUREMENTS AND MAIN RESULTS: Postoperative outcomes were myocardial infarction, renal replacement therapy, stroke, and death. With propensity matching, the authors optimized exchangeability of the compared groups. Adverse outcomes increased with a decreasing Hb both among Witnesses and among non-Witnesses. The incidence of postoperative complications did not differ between Witnesses and matched non Witnesses who received RBC (adjusted odds ratio 1.44, 95% confidence interval 0.63-3.29). Similarly, postoperative complications did not differ between patients who received a red cell transfusion and matched patients who did not (adjusted odds ratio 0.94, confidence interval 0.72-1.23). CONCLUSION: Intraoperative anemia is associated with adverse outcomes after cardiac surgery, and a single RBC transfusion does not seem to influence these outcomes. PMID- 26809767 TI - Response to Letter to the Editor: "Risk factors for postoperative pneumonia after lung cancer surgery and impact of pneumonia on survival". PMID- 26809768 TI - A Diagnosis to Consider in Intellectual Disability: Mowat-Wilson Syndrome. AB - Mowat-Wilson syndrome is a multiple congenital anomaly and intellectual disability syndrome characterized by a unique face and various other structural and functional anomalies. The condition is caused by de novo heterozygous mutations or deletions in ZEB2 gene located at 2q22. ZEB2 encodes Sip1 protein, which acts during central nervous system development as an important transcription factor. Herein, we report on 3 novel mutations in 6 patients with the syndrome, with an overview of corresponding clinical findings. Growth retardation and Hirschsprung disease were less common in the present cohort. One patient with a novel mutation p.Y489X had no associated anomalies except the characteristic facial and neurobehavioral phenotype. Reporting new patients with novel mutations would contribute to better delineation of the syndrome and would help clinicians establish formal diagnostic criteria and genotype-phenotype correlations. PMID- 26809769 TI - Measles: A Canary in the Coal Mines? PMID- 26809770 TI - Inclusion of cytological features in tumor grading improves prognostic stratification of patients with colorectal cancer. AB - PURPOSE: Tumor grade is a traditional prognostic parameter in colorectal cancer. Remarkably, however, there is still no generally accepted consensus how to perform tumor grading. In this study, we systematically compared the prognostic value of traditional grading based upon histological features, that is, gland formation alone with grading based upon both histological and cytological features, such as nuclear pleomorphism and anaplasia ("alternative grade"). METHODS: Three hundred eighty-one tumors of randomly selected patients were retrospectively reviewed. Traditional and alternative tumor grades were related to various clinicopathological features and to progression-free and cancer specific survival applying both univariate and multivariate testing. RESULTS: Traditional and alternative tumor grades were significantly associated with T and N classification, tumor size, lymphovascular invasion, as well as both progression-free and cancer-specific survival. In Cox's proportional hazards regression models, the alternative grade was superior to the traditional tumor grade and was significantly associated with progression-free survival (hazard ratio 1.57, 95% confidence interval 1.04-2.35; p = 0.031), independent of patients' age and gender, T and N classification, and lymphovascular invasion. Likewise, patients with tumors with high alternative grade were more likely to die of disease (hazard ratio 1.30, 95% confidence interval 0.85-2.00), but this difference was not statistically significant (p = 0.22). CONCLUSIONS: Tumor grade based upon both histological and cytological features was superior to grade based upon histological features alone and proved to be an independent prognostic parameter. Thus, tumor grade based upon both histological and cytological features may help to improve prognostic stratification and may thereby affect clinical decision-making and patient management. PMID- 26809771 TI - Mesenteric defect after laparoscopic left hemicolectomy: to close or not to close? PMID- 26809772 TI - 2015 ACR/ACC/AHA/AATS/ACEP/ASNC/NASCI/SAEM/SCCT/SCMR/SCPC/SNMMI/STR/STS Appropriate Utilization of Cardiovascular Imaging in Emergency Department Patients With Chest Pain: A Joint Document of the American College of Radiology Appropriateness Criteria Committee and the American College of Cardiology Appropriate Use Criteria Task Force. PMID- 26809773 TI - Impact of host genetic polymorphisms on vaccine induced antibody response. AB - Many host- and vaccine-specific factors modulate an antibody response. Host genetic polymorphisms, in particular, modulate the immune response in multiple ways on different scales. This review article describes how information on host genetic polymorphisms and corresponding immune cascades may be used to generate personalized vaccine strategies to optimize the antibody response. PMID- 26809774 TI - Applying computation biology and "big data" to develop multiplex diagnostics for complex chronic diseases such as osteoarthritis. AB - The data explosion in the last decade is revolutionizing diagnostics research and the healthcare industry, offering both opportunities and challenges. These high throughput "omics" techniques have generated more scientific data in the last few years than in the entire history of mankind. Here we present a brief summary of how "big data" have influenced early diagnosis of complex diseases. We will also review some of the most commonly used "omics" techniques and their applications in diagnostics. Finally, we will discuss the issues brought by these new techniques when translating laboratory discoveries to clinical practice. PMID- 26809775 TI - Commercial Truck Driver Health and Safety: Exploring Distracted Driving Performance and Self-Reported Driving Skill. AB - Reducing distracters detrimental to commercial truck driving is a critical component of improving the safety performance of commercial drivers, and makes the highways safer for all drivers. This study used a driving simulator to examine effects of cell phone, texting, and email distractions as well as self reported driver optimism bias on the driving performance of commercial truck drivers. Results revealed that more visually demanding tasks were related to poorer driving performance. However, the cell phone task resulted in less off-the road eye glances. Drivers reporting being "very skilled" displayed poorer driving performance than those reporting being "skilled." Onboard communication devices provide a practical, yet visually and manually demanding, solution for connecting drivers and dispatchers. Trucking company policies should minimize interaction between dispatchers and drivers when the truck is in motion. Training facilities should integrate driving simulators into the instruction of commercial drivers, targeting over-confident drivers. PMID- 26809776 TI - Increasing the Richness of Culturable Arsenic-Tolerant Bacteria from Theonella swinhoei by Addition of Sponge Skeleton to the Growth Medium. AB - Theonella swinhoei is an arsenic hyper-accumulator sponge, harboring a multitude of associated bacteria. These bacteria reside in the mesohyl, the dense extracellular matrix of the sponge. Previous elemental analysis of separated cell fractions from the sponge had determined that arsenic is localized to the associated bacteria. Subsequently, sponge-associated arsenic-tolerant bacteria were isolated here and grouped into 15 operational taxonomic units (OTUs, 97% similarity). Both culture-dependent and culture-independent work had revealed that T. swinhoei harbors a highly diverse bacterial community. It was thus hypothesized the acclimation of bacteria in the presence of a sponge skeleton, better mimicking its natural environment, would increase the yield of isolation of sponge-associated bacteria. Using seven modularly designed media, 380 bacteria isolates were grown and grouped into 22 OTUs. Inclusion of sponge skeleton in the growth medium promoted bacterial growth in all seven media, accounting for 20 of the 22 identified OTUs (the other two in a medium without skeleton). Diversity and richness indices were calculated for each treatment or combination of treatments with shared growth parameters. Integrating data inherent in the modularly designed media with the ecological indices led to the formation of new hypotheses regarding the aeration conditions and expected arsenic form in situ. Both aerobic and anoxic conditions are expected to occur in the sponge (temporally and/or spatially). Arsenate is expected to be the dominant (or even the only) arsenic form in the sponge. PMID- 26809777 TI - ADAMTS-4 promotes neurodegeneration in a mouse model of amyotrophic lateral sclerosis. AB - BACKGROUND: A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) proteoglycanases are specialized in the degradation of chondroitin sulfate proteoglycans and participate in mechanisms mediating neuroplasticity. Despite the beneficial effect of ADAMTS-4 on neurorepair after spinal cord injury, the functions of ADAMTS proteoglycanases in other CNS disease states have not been studied. Therefore, we investigated the expression, effects and associated mechanisms of ADAMTS-4 during amyotrophic lateral sclerosis (ALS) in the SOD1(G93A) mouse model. RESULTS: ADAMTS-4 expression and activity were reduced in the spinal cord of SOD1(G93A) mice at disease end-stage when compared to WT littermates. To counteract the loss of ADAMTS-4, SOD1(G93A) and WT mice were treated with saline or a recombinant ADAMTS-4 before symptom onset. Administration of ADAMTS-4 worsened the prognosis of SOD1(G93A) mice by accelerating clinical signs of neuromuscular dysfunctions. The worsened prognosis of ADAMTS-4-treated SOD1(G93A) mice was accompanied by increased degradation of perineuronal nets enwrapping motoneurons and increased motoneuron degeneration in the lumbar spinal cord. Motoneurons of ADAMTS-4-treated SOD1(G93A) mice were more vulnerable to degeneration most likely due to the loss of their extracellular matrix envelopes. The decrease of neurotrophic factor production induced by ADAMTS-4 in vitro and in vivo may also contribute to a hostile environment for motoneuron especially when devoid of a net. CONCLUSIONS: This study suggests that the reduction of ADAMTS-4 activity during the progression of ALS pathology may be an adaptive change to mitigate its neurodegenerative impact in CNS tissues. Therapies compensating the compromized ADAMTS-4 activity are likely not promising approaches for treating ALS. PMID- 26809778 TI - Mendelian Randomization and Type 2 Diabetes. AB - Type 2 diabetes (T2DM) is a common, complex disease that poses a substantial burden on individual and population health, but we have relatively limited understanding of its underlying pathophysiology. Observational studies have highlighted large numbers of risk factors for T2DM, some of which are modifiable through behavioural or pharmacological intervention. Determining which of these risk factors plays a causal role in the development of T2DM has been a challenge, but Mendelian randomisation (MR) studies are harnessing genetic data in population studies to offer new insights. Using evolving analytical methods, MR studies continue to address questions of causality related to T2DM, including exploring the roles of adiposity, blood lipids and inflammation. The causal roles of a number of important modifiable risk factors have been confirmed by MR studies, while the relevance of others has been called into question. As more MR studies are conducted, methods are developed and refined in order to make the most efficient and reliable use of available genetic and phenotypic data. In this review, the design and findings of some important MR studies related to T2DM are explored and their relevance for translation to clinical practice considered. PMID- 26809780 TI - Engineering Synthetic Gene Circuits in Living Cells with CRISPR Technology. AB - One of the goals of synthetic biology is to build regulatory circuits that control cell behavior, for both basic research purposes and biomedical applications. The ability to build transcriptional regulatory devices depends on the availability of programmable, sequence-specific, and effective synthetic transcription factors (TFs). The prokaryotic clustered regularly interspaced short palindromic repeat (CRISPR) system, recently harnessed for transcriptional regulation in various heterologous host cells, offers unprecedented ease in designing synthetic TFs. We review how CRISPR can be used to build synthetic gene circuits and discuss recent advances in CRISPR-mediated gene regulation that offer the potential to build increasingly complex, programmable, and efficient gene circuits in the future. PMID- 26809781 TI - Super-fast synthesis of ZnO nanowires by microwave air-plasma. AB - Microwave radiation is focussed on the sharp edges of the Zn swarf. Plasma is produced by a microwave under atmospheric conditions and successfully used to synthesize ZnO nanowires and ZnO nanoparticles. The fabrication setup is very simple but extremely fast and effective. The sharp Zn swarf is irradiated by the microwave and is ignited and sputtered by the air plasma with a very high oxidization and crystallization rate. PMID- 26809782 TI - The Association Between a Sense of Calling and Physician Well-Being: A National Study of Primary Care Physicians and Psychiatrists. AB - OBJECTIVE: This study assesses the association between calling and physician well being, clinical commitment, and burnout. METHODS: In 2009-2010, a survey was mailed to 1504 primary care physicians (PCPs) and 512 psychiatrists drawn from the American Medical Association Physician Masterfile. The primary independent variable was a single-item measure that assessed physicians' level of calling. Main outcomes were markers of physician well-being (career satisfaction and morale), clinical commitment (intentions to reduce time spent in direct patient care, leave practice in a few years), and experiences of burnout. RESULTS: Adjusted response rates were 63 % (896/1427) for PCPs and 64 % (312/487) for psychiatrists. Forty-two percent of US PCPs and psychiatrists agree strongly that their practice of medicine is a calling. Physicians with a high sense of calling were less likely than those with low to report regret in choosing medicine as a career (18 vs. 38 %; odds ratio 0.3; 95 % confidence interval, 0.2-0.5), wanting to go into a different clinical specialty (28 vs. 49 %; OR 0.4; 95 % CI, 0.2 0.6), or wanting to leave the practice of medicine in the next few years (14 vs. 25 %, OR 0.4; 95 % CI 0.2-0.7). Physicians with a high sense of calling were less likely to report burnout (17 vs. 31 % low calling, OR 0.4; 95 % CI 0.3 to 0.7). CONCLUSIONS: Physicians who reported that medicine was a calling may be experiencing higher levels of career satisfaction, more durable clinical commitments, and resilience from burnout. Though physicians may differ on their understanding of the concept of calling in medicine, this study highlights an important factor that should be investigated further when assessing long-term workforce retention in the fields of primary care and psychiatry. PMID- 26809779 TI - DNA methylation in peripheral tissue of schizophrenia and bipolar disorder: a systematic review. AB - BACKGROUND: Increasing evidence suggests the involvement of epigenetic processes in the development of schizophrenia and bipolar disorder, and recent reviews have focused on findings in post-mortem brain tissue. A systematic review was conducted to synthesise and evaluate the quality of available evidence for epigenetic modifications (specifically DNA methylation) in peripheral blood and saliva samples of schizophrenia and bipolar disorder patients in comparison to healthy controls. METHODS: Original research articles using humans were identified using electronic databases. There were 33 included studies for which data were extracted and graded in duplicate on 22 items of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement, to assess methodological precision and quality of reporting. RESULTS: There were 15 genome wide and 18 exclusive candidate gene loci investigations for DNA methylation studies. A number of common genes were identified as differentially methylated in schizophrenia/bipolar disorder, which were related to reelin, brain-derived neurotrophic factor, dopamine (including the catechol-O-methyltransferase gene), serotonin and glutamate, despite inconsistent findings of hyper-, hypo-, or lack of methylation at these and other loci. The mean STROBE score of 59% suggested moderate quality of available evidence; however, wide methodological variability contributed to a lack of consistency in the way methylation levels were quantified, such that meta-analysis of the results was not possible. CONCLUSIONS: Moderate quality of available evidence shows some convergence of differential methylation at some common genetic loci in schizophrenia and bipolar disorder, despite wide variation in methodology and reporting across studies. Improvement in the clarity of reporting clinical and other potential confounds would be useful in future studies of epigenetic processes in the context of exposure to environmental and other risk factors. PMID- 26809783 TI - Topical amitriptyline and ketamine for post-herpetic neuralgia and other forms of neuropathic pain. AB - INTRODUCTION: Neuropathic pain (NP) has several therapeutic options but efficacy is limited and adverse effects occur, such that additional treatment options are needed. A topical formulation containing amitriptyline 4% and ketamine 2% (AmiKet) may provide such an option. AREAS COVERED: This report summarizes both published and unpublished results of clinical trials with AmiKet. In post herpetic neuralgia (PHN), AmiKet produces a significant analgesia which is comparable to that produced by oral gabapentin. In diabetic painful neuropathy, AmiKet showed a strong trend towards pain reduction. In mixed neuropathic pain, case series reports suggest a favourable response rate, but are limited by trial characteristics. AmiKet is absorbed minimally following topical administration. Over 700 patients have now received topical AmiKet in clinical regimens, and it is well-tolerated with the adverse effects mainly being application site reactions. Both agents are polymodal, and several mechanisms may contribute to the peripheral efficacy of AmiKet. EXPERT OPINION: Topical AmiKet has the potential to be a first-line treatment option for PHN, and to be useful in other NP conditions. Furthermore, AmiKet has the potential to be an adjunct to systemic therapies, with the targeting of a peripheral compartment in addition to central sites of action representing a rational drug combination. PMID- 26809786 TI - Where is the Bullet? PMID- 26809787 TI - Acute Type A Aortic Dissection. PMID- 26809788 TI - Editorial overview: Growth and development: Signals and communication in plant pluripotency, differentiation and growth. PMID- 26809791 TI - 2016--Leaping (and looking) ahead. PMID- 26809792 TI - Currents through Hv1 channels deplete protons in their vicinity. AB - Proton channels have evolved to provide a pH regulatory mechanism, affording the extrusion of protons from the cytoplasm at all membrane potentials. Previous evidence has suggested that channel-mediated acid extrusion could significantly change the local concentration of protons in the vicinity of the channel. In this work, we directly measure the proton depletion caused by activation of Hv1 proton channels using patch-clamp fluorometry recordings from channels labeled with the Venus fluorescent protein at intracellular domains. The fluorescence of the Venus protein is very sensitive to pH, thus behaving as a genetically encoded sensor of local pH. Eliciting outward proton currents increases the fluorescence intensity of Venus. This dequenching is related to the magnitude of the current and not to channel gating and is dependent on the pH gradient. Our results provide direct evidence of local proton depletion caused by flux through the proton-selective channel. PMID- 26809795 TI - [Adherence to international recommendations in the fight against antimicrobial resistance - Substantial difference between outpatient consumption in Spain and Denmark]. AB - OBJECTIVE: Increasing antibiotic resistance represents a major public health threat that jeopardises the future treatment of bacterial infections. This study aims to describe the adherence to recommendations proposed by the World Health Organization (WHO) Advisory Group on Integrated Surveillance of Antimicrobial Resistance (AGISAR), in Spain and Denmark, and to analyse the relation between the outpatient use of Critically Important Antimicrobials (CIA) and the bacterial resistance rates to these agents. METHODS: The Antimicrobial consumption interactive database (ESAC-Net) and Antimicrobial resistance interactive database (EARS-Net) provided data on outpatient use (2010-2013) of CIA (fluoroquinolones, macrolides, and 3rd and 4th generation cephalosporins) and the percentages of isolates of the main pathogens causing serious infections, resistant to these agents. RESULTS: The use of cephalosporins and fluoroquinolones, as well as the percentage of bacteria resistant, is higher in Spain than in Denmark. Although consumption of macrolides in both countries is similar, the proportion of Streptococcus pneumoniae resistant to macrolides is significantly higher in Spain. CONCLUSIONS: The high outpatient consumption of CIA agents in Spain deviates substantially from the WHO recommendations. Moreover, it has the effect of elevated rates of antimicrobial resistance, that are lower in Denmark. PMID- 26809794 TI - The inactivation domain of STIM1 is functionally coupled with the Orai1 pore to enable Ca2+-dependent inactivation. AB - The inactivation domain of STIM1 (ID(STIM): amino acids 470-491) has been described as necessary for Ca(2+)-dependent inactivation (CDI) of Ca(2+) release activated Ca(2+) (CRAC) channels, but its mechanism of action is unknown. Here we identify acidic residues within IDSTIM that control the extent of CDI and examine functional interactions of ID(STIM) with Orai1 pore residues W76 and Y80. Alanine scanning revealed three IDSTIM residues (D476/D478/D479) that are critical for generating full CDI. Disabling ID(STIM) by a triple alanine substitution for these three residues ("STIM1 3A") or by truncation of the entire domain (STIM1(1 469)) reduced CDI to the same residual level observed for the Orai1 pore mutant W76A (approximately one third of the extent seen with full-length STIM1). Results of noise analysis showed that STIM11-469 and Orai1 W76A mutants do not reduce channel open probability or unitary Ca(2+) conductance, factors that determine local Ca(2+) accumulation, suggesting that they diminish CDI instead by inhibiting the CDI gating mechanism. We tested for functional coupling between ID(STIM) and the Orai1 pore by double-mutant cycle analysis. The effects on CDI of mutations disabling ID(STIM) or W76 were not additive, demonstrating that ID(STIM) and W76 are strongly coupled and act in concert to generate full strength CDI. Interestingly, disabling ID(STIM) and W76 separately gave opposite results in Orai1 Y80A channels: channels with W76 but lacking ID(STIM) generated approximately two thirds of the WT extent of CDI but those with ID(STIM) but lacking W76 completely failed to inactivate. Together, our results suggest that Y80 alone is sufficient to generate residual CDI, but acts as a barrier to full CDI. Although ID(STIM) is not required as a Ca(2+) sensor for CDI, it acts in concert with W76 to progress beyond the residual inactivated state and enable CRAC channels to reach the full extent of inactivation. PMID- 26809793 TI - Orai1 pore residues control CRAC channel inactivation independently of calmodulin. AB - Ca(2+) entry through CRAC channels causes fast Ca(2+)-dependent inactivation (CDI). Previous mutagenesis studies have implicated Orai1 residues W76 and Y80 in CDI through their role in binding calmodulin (CaM), in agreement with the crystal structure of Ca(2+)-CaM bound to an Orai1 N-terminal peptide. However, a subsequent Drosophila melanogaster Orai crystal structure raises concerns about this model, as the side chains of W76 and Y80 are predicted to face the pore lumen and create a steric clash between bound CaM and other Orai1 pore helices. We further tested the functional role of CaM using several dominant-negative CaM mutants, none of which affected CDI. Given this evidence against a role for pretethered CaM, we altered side-chain volume and charge at the Y80 and W76 positions to better understand their roles in CDI. Small side chain volume had different effects at the two positions: it accelerated CDI at position Y80 but reduced the extent of CDI at position W76. Positive charges at Y80 and W76 permitted partial CDI with accelerated kinetics, whereas introducing negative charge at any of five consecutive pore-lining residues (W76, Y80, R83, K87, or R91) completely eliminated CDI. Noise analysis of Orai1 Y80E and Y80K currents indicated that reductions in CDI for these mutations could not be accounted for by changes in unitary current or open probability. The sensitivity of CDI to negative charge introduced into the pore suggested a possible role for anion binding in the pore. However, although Cl(-) modulated the kinetics and extent of CDI, we found no evidence that CDI requires any single diffusible cytosolic anion. Together, our results argue against a CDI mechanism involving CaM binding to W76 and Y80, and instead support a model in which Orai1 residues Y80 and W76 enable conformational changes within the pore, leading to CRAC channel inactivation. PMID- 26809796 TI - [Dual therapy as an alternative treatment in HIV pretreated patients: experience in a tertiary hospital]. AB - OBJECTIVE: Dual therapy regimen might be an effective alternative to prevent the occurrence of side effects and comorbidities associated with prolonged treatment with antiretroviral (ARV) and a way of simplification of antiretroviral therapy (ART) to improve adherence in certain patients. It also represents a potential treatment option for patients who have failed previous TAR. METHODS: The aim of the study is to describe the effectiveness, adherence and costs of dual therapy regimen used in pretreated HIV patients in tertiary hospital. RESULTS: Thirty eight patients were studied (eight were excluded). Reasons for simplification to dual therapy were previous treatment toxicity (40%), simplification (36.67%) and virological rescue (20%). The dual therapy regimens most used were: IP/r + INSTIs (26.67%), IP/r + NRTIs (23.33%), IP/r + NNR-TIs (23.33%), IP/r+ CCR5 (16.66%) e INSTIs + NNRTIs (10%). ARV more used were darunavir/ritonavir (DRV/r) + raltegravir (23.33 %); DRV/r + lamivudine (20%) y DRV/r + etravirine (16.67 %). Adherence was 86.79% before switching to dual therapy and 96.27% after switching. The cost savings of switching to dual therapy of these patients was ? 3,635.16. CONCLUSIONS: Dual therapy with IP/r might be an effective alternative to selected treatment experienced patients compared with conventional therapy. PMID- 26809797 TI - Predictive factors of abatacept therapy discontinuation in patients with rheumatoid arthritis. AB - The aim of this paper was to look for predictors of abatacept (ABA) therapy discontinuation in patients with rheumatoid arthritis (RA). Seventy-one RA patients treated with ABA were followed up. Demographical, clinical, and laboratory parameters of the patients, including peripheral blood T and B cell populations, different rheumatoid factor and anti-cyclic citrullinated peptide autoantibodies isotypes, and serum free light chains were evaluated. Comparing patients who discontinued ABA with those still in therapy we observed: a higher proportion of smokers (51.9 vs 25.6 %; p = 0.03); a non significant lower proportion of anti-cyclic citrullinated peptide positivity (76 vs 89.5 %; p = 0.13); a lower proportion of terminally differentiated effector memory cells (TDEM) among total CD8+ T lymphocytes at baseline (22.0 % (7.8-39.2) vs 38.7 % (20.7-55.9); p = 0.002). Logistic multivariate analysis showed that only the proportion of CD8+TDEM T cells was an independent predictive factor of therapy discontinuation (OR (95 % IC) = 6.2 (1.2 to 30.8); p = 0.026). Receiver-operating characteristic analysis showed a significant performance of this biomarker for prediction of therapy discontinuation (using a cut-off of 30.6 %: AUC: 0.760 +/- 0.07; p = 0.002). Patients with a low proportion of CD8+TDEM at baseline had a higher probability of discontinuing the treatment during time (log-rank test: p < 0.01). T cell characterization for identification of TDEM CD8+ T cells might be a useful test to predict discontinuation of ABA therapy. PMID- 26809798 TI - Clinical characteristics and follow-up analysis of adult-onset Still's disease complicated by hemophagocytic lymphohistiocytosis. AB - We evaluated clinical characteristics and prognosis for adult-onset Still's disease (AOSD) complicated by hemophagocytic lymphohistiocytosis (HLH). We retrospectively identified cases of AOSD with (n = 10) and without (n = 305) HLH complications. We reviewed their medical records, completed follow-up through outpatient clinic and telephone interviews, and analyzed their clinical symptoms, signs, laboratory test results, treatments, and prognosis. More AOSD patients with HLH developed hepatomegaly, bleeding, serositis, and neurologic symptoms than those without HLH, and they more commonly presented with leukopenia, thrombocytopenia, severe anemia, severe liver function abnormalities, decreased fibrinogen, elevated immunoglobulin, and bone marrow hemophagocytosis. The ten patients with AOSD complicated by HLH were treated with high-dose steroids or pulse steroid therapy, and eight of them also received cytotoxic drugs, while biological agents showed poor response. Follow-up results indicated that AOSD patients overall had good prognosis, while those with HLH showed worse prognosis, including higher relapse and readmission rates and increased mortality. In patients with AOSD, unexplained decreased blood cells, severe liver dysfunction, and/or hemophagocytosis in the bone marrow should be considered as signs of HLH complication. Patients with AOSD complicated by HLH have worse prognosis and higher relapse rates compared to AOSD patients without HLH complications. Thus, these patients should undergo frequent and careful follow-up. PMID- 26809799 TI - Younger patients with primary Sjogren's syndrome are more likely to have salivary IgG anti-muscarinic acetylcholine receptor type 3 antibodies. AB - Acetylcholine type 3 receptor (M3R) is recognized as an autoantigen in primary Sjogren's syndrome (pSS). Assay of anti-M3R antibody levels in serum is fraught with low sensitivity for diagnosis of pSS. Salivary assay is more likely to improve the diagnostic accuracy. Patients with pSS classified either by the American European Consensus Group (AECG) or American college of Rheumatology (ACR) criteria, attending rheumatology clinic between October 2014 and July 2015 were included. Hospital staff and lupus patients constituted healthy and disease controls, respectively. Evaluation of pSS included clinical evaluation, laboratory tests, ESSDAI and ESSPRI scoring. Unstimulated saliva was collected by the spitting method. Salivary IgG antibody against M3R (anti-M3R) was quantified by indirect ELISA. In this study, 43 patients with pSS, 34 with lupus and 42 healthy controls were recruited. The frequency of anti-M3R antibody levels was 55.81, 17.64 and 7 % for pSS, lupus and healthy controls, respectively. Area under the Receiver Operator Characteristic was 0.7791 (95 % CI,, 0.67-0.87). Sensitivity and specificity of the assay for diagnosis of pSS were 44.19 and 88.16 %, respectively. Salivary anti-M3R IgG antibody positivity was associated with lower age, shorter disease duration and higher globulin levels in our cohort. Salivary anti-M3R IgG antibody assay has high specificity in pSS; younger patients and those with hyperglobulinemia more frequently tested positive for this antibody. PMID- 26809800 TI - Glucosyl Rubusosides by Dextransucrases Improve the Quality of Taste and Sweetness. AB - Glucosyl rubusosides were synthesized by two dextransucrases. LcDexT was obtained from Leuconosotoc citreum, that LlDexT was obtained from Leuconostoc lactis. LcDexT and LlDexT regioselectively transferred a glucosyl residue to the 13-O glucosyl moiety of rubusoside with high yield of 59-66% as analyzed by TLC and HPLC. Evaluation of the sweetness of these glucosyl rubusosides showed that their quality of taste, in particular, was superior to that of rubusoside. These results indicate that transglucosylation at the 13-O-glucosyl moiety of rubusoside by different regioselective dextransucrases can be applicable for increasing its sweetness and quality of taste. PMID- 26809801 TI - Potassium Acetate Blocks Clostridium difficile Toxin A-Induced Microtubule Disassembly by Directly Inhibiting Histone Deacetylase 6, Thereby Ameliorating Inflammatory Responses in the Gut. AB - Clostridium difficile toxin A is known to cause deacetylation of tubulin proteins, which blocks microtubule formation and triggers barrier dysfunction in the gut. Based on our previous finding that the Clostridium difficile toxin A dependent activation of histone deacetylase 6 (HDAC-6) is responsible for tubulin deacetylation and subsequent microtubule disassembly, we herein examined the possible effect of potassium acetate (PA; whose acetyl group prevents the binding of tubulin to HDAC-6) as a competitive/false substrate. Our results revealed that PA inhibited toxin A-induced deacetylation of tubulin and recovered toxin A induced microtubule disassembly. In addition, PA treatment significantly decreased the production of IL-6 (a marker of inflamed tissue) in the toxin A induced mouse enteritis model. An in vitro HDAC assay revealed that PA directly inhibited HDAC-6-mediated tubulin deacetylation, indicating that PA acted as a false substrate for HDAC-6. These results collectively indicate that PA treatment inhibits HDAC-6, thereby reducing the cytotoxicity and inflammatory responses caused by C. difficile toxin A. PMID- 26809802 TI - A Detrimental Role of Immunosuppressive Drug, Dexamethasone, During Clostridium difficile Infection in Association with a Gastrointestinal Microbial Shift. AB - We investigated the increased risk of Clostridium difficile infection (CDI) caused by the combined use of antibiotics and an immunosuppressive drug in a mouse model. Our data showed that an approximate return to pretreatment conditions of gut microbiota occurred within days after cessation of the antibiotic treatment, whereas the recovery of gut microbiota was delayed with the combined treatment of antibiotics and dexamethasone, leading to an increased severity of CDI. An alteration of gut microbiota is a key player in CDI. Therefore, our data implied that immunosuppressive drugs can increase the risk of CDI through the delayed recovery of altered gut microbiota. PMID- 26809803 TI - Diversity of the Gastric Microbiota in Thoroughbred Racehorses Having Gastric Ulcer. AB - Equine gastric ulcer syndrome is one of the most frequently reported diseases in thoroughbred racehorses. Although several risk factors for the development of gastric ulcers have been widely studied, investigation of microbiological factors has been limited. In this study, the presence of Helicobacter spp. and the gastric microbial communities of thoroughbred racehorses having mild to severe gastric ulcers were investigated. Although Helicobacter spp. were not detected using culture and PCR techniques from 52 gastric biopsies and 52 fecal samples, the genomic sequences of H. pylori and H. ganmani were detected using nextgeneration sequencing techniques from 2 out of 10 representative gastric samples. The gastric microbiota of horses was mainly composed of Firmicutes (50.0%), Proteobacteria (18.7%), Bacteroidetes (14.4%), and Actinobacteria (9.7%), but the proportion of each phylum varied among samples. There was no major difference in microbial composition among samples having mild to severe gastric ulcers. Using phylogenetic analysis, three distinct clusters were observed, and one cluster differed from the other two clusters in the frequency of feeding, amount of water consumption, and type of bedding. To the best of our knowledge, this is the first study to investigate the gastric microbiota of thoroughbred racehorses having gastric ulcer and to evaluate the microbial diversity in relation to the severity of gastric ulcer and management factors. This study is important for further exploration of the gastric microbiota in racehorses and is ultimately applicable to improving animal and human health. PMID- 26809804 TI - The path to chronic kidney disease following acute kidney injury: a neonatal perspective. AB - The risk of acute kidney injury (AKI) in hospitalized critically ill neonatal populations without primary renal disease continues to be high, in both term and premature infants. Observational studies have revealed high rates of chronic kidney disease (CKD) in survivors of neonatal AKI. Proposed mechanisms underlying the progression of CKD following AKI include nephron loss and hyperfiltration, vascular insufficiency and maladaptive repair mechanisms. Other factors, including prematurity and low birth weight, have an independent relationship with the development of CKD, but they may also be positive effect modifiers in the relationship of AKI and CKD. The large degree of heterogeneity in the literature on AKI in the neonatal population, including the use of various AKI definitions and CKD outcomes, has hampered the medical community's ability to properly assess the relationship of AKI and CKD in this vulnerable population. Larger prospective cohort studies with control groups which utilize recently proposed neonatal AKI definitions and standardized CKD definitions are much needed to properly quantify the risk of CKD following an episode of AKI. Until there is further evidence to guide us, we recommend that all neonates with an identified episode of AKI should have an appropriate longitudinal follow-up in order to identify CKD at its earliest stages. PMID- 26809805 TI - Identification of 47 novel mutations in patients with Alport syndrome and thin basement membrane nephropathy. AB - BACKGROUND: Alport syndrome (ATS) is a progressive hereditary nephropathy characterized by hematuria and proteinuria. It can be associated with extrarenal manifestations. In contrast, thin basement membrane nephropathy (TBMN) is characterized by microscopic hematuria, is largely asymptomatic, and is rarely associated with proteinuria and end-stage renal disease. Mutations have been identified in the COL4A5 gene in ATS and in the COL4A3 and COL4A4 genes in ATS and TBMN. To date, more than 1000 different mutations in COL4A5, COL4A3, and COL4A4 are known. METHODS: In this study mutational analysis by exon sequencing and multiplex ligation-dependent probe amplification was performed in a large European cohort of families with ATS and TBMN. RESULTS: Molecular diagnostic testing of 216 individuals led to the detection of 47 novel mutations, thereby expanding the spectrum of known mutations causing ATS and TBMN by up to 10 and 6%, respectively, depending on the database. Remarkably, a high number of ATS patients with only single mutations in COL4A3 and COL4A4 were identified. Additionally, three ATS patients presented with synonymous sequence variants that possible affect correct mRNA splicing, as suggested by in silico analysis. CONCLUSIONS: The results of this study clearly broaden the genotypic spectrum of known mutations for ATS and TBMN, which will in turn now facilitate future studies into genotype-phenotype correlations. Further studies should also examine the significance of single heterozygous mutations in COL4A3 and COL4A4 and of synonymous sequence variants associated with ATS. PMID- 26809806 TI - Longitudinal analysis of serum cystatin C for estimating the glomerular filtration rate in preterm infants. AB - BACKGROUND: Cystatin C (Cys-C) is a more sensitive marker of renal function than creatinine (Cre) in pediatric and adult populations. However, the reference values of serum Cys-C for estimating glomerular filtration rates (eGFRs) in premature infants during the first year of life have not been sufficiently studied. METHODS: In this prospective study, 481 blood samples were collected from 261 preterm infants with uncomplicated clinical courses during their first year of life. Infants were divided into three groups according to gestational age at birth: 27-30 weeks, 31-33 weeks, and 34-36 weeks. Serum Cys-C and Cre levels were measured at 6-30 days, 3-5 months, 7-9 months, and 12-14 months after birth and the eGFR was calculated using two previously published equations. RESULTS: The median serum Cys-C levels were 1.776, 1.248, 1.037, and 0.960 mg/L at the first, second, third, and fourth measurement time-point, respectively, with the value significantly decreasing with age up to 12-14 months. Cys-C levels were independent of gestational age and gender. In contrast to Cys-C, serum Cre values declined rapidly up to 3-5 months, then remained constant up to 12-14 months. Using the Cys-C-based equation, the eGFR significantly increased with increasing age until approximately 1 year after birth; however, no such trend was noted using the equation based on Cys-C + Cre. CONCLUSIONS: Reference ranges for Cys-C in premature infants decline gradually over the first year after birth. Cys-C appears to be a more reliable marker than Cre for estimating GFR in preterm infants. PMID- 26809808 TI - Self-Assembly-Assisted Biomolecule-Enriched Surface and High Selectivity Performance of Simple Solution-Coatable Biomimicking Brush Copolymers. AB - Poly(oxy(11-(biotinyl)undecylthiomethyl)ethylene-co-oxy(11-phosphoryl cholineundecylthiomethyl)ethylene)s (PECH-BTmPCn: m = 0-100 mol % biotin (BT) containing bristle; n = 100-0 mol % phosphorylcholine (PC)-containing bristle) were newly synthesized. All polymers exhibited excellent solution processability. They favorably self-assembled horizontal multibilayer structures in thin films with BT- and PC-enriched surfaces, which were driven by the lateral ordering of the fully extended upright bristles and the partial interdigitation between the BT and PC end groups of the bristles. Both hydrophilicity and water sorption of the films increased with the PC content. The PECH-BT100 films revealed remarkably distinctive sensitivity, selectivity, and adsorption ability for avidin against other proteins. Such remarkable performance was further significantly enhanced on the PECH-BTmPCn films in which PC moieties were incorporated to the BT-rich surface; in particular, the PECH-BT75PC25 films demonstrated the highest performance. Overall, the self-assembly brush copolymers of this study are very suitable for use in the high performance detection, adsorption, and separation of proteins and receptors, including avidin, which can reveal high affinity and selectivity to BT moiety. PMID- 26809811 TI - Macroscopic fibres of CNTs as electrodes for multifunctional electric double layer capacitors: from quantum capacitance to device performance. AB - In this work we present a combined electrochemical and mechanical study of mesoporous electrodes based on CNT fibres in the context of electric double layer capacitors. We show that through control of the synthetic and assembly processes of the fibres, it is possible to obtain an active material that combines a surface area of 250 m(2) g(-1), high electrical conductivity (3.5 * 10(5) S m( 1)) and mechanical properties in the high-performance range including toughness (35 J g(-1)) comparable to that of aramid fibre (e.g. Kevlar). These properties are a consequence of the predominant orientation of the CNTs, observed by wide- and small-angle X-ray diffraction, and to the exceptionally long CNT length on the millimetre scale. Cyclic voltammetry measurements in a three-electrode configuration and using 1-butyl-3-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (PYR14TFSI) ionic liquid electrolyte, show that the CNT fibres have a large quantum capacitance, evidenced by the near linear dependence of geometric capacitance (and conductivity) on potential bias. This reflects the low dimensionality of the CNT building blocks, which were purposely synthesised to have 1-5 layers and a high degree of graphitization. From the charge-discharge measurements of supercapacitor devices with symmetric CNT fibre electrodes we obtain power and energy densities as high as 58 kW kg(-1) and 14 Wh kg(-1), respectively. These record-high values for CNT fibre-based supercapacitors, are a consequence of the low equivalent series resistance due to the high conductivity of the fibres, the large contribution from quantum capacitance, and the wide stability window of the ionic liquid (3.5 V). Cycle life experiments demonstrate stable capacitance and energy retention over 10,000 cycles of charge-discharge at 3.5 V. PMID- 26809812 TI - Multiple imputation of multiple multi-item scales when a full imputation model is infeasible. AB - BACKGROUND: Missing data in a large scale survey presents major challenges. We focus on performing multiple imputation by chained equations when data contain multiple incomplete multi-item scales. Recent authors have proposed imputing such data at the level of the individual item, but this can lead to infeasibly large imputation models. METHODS: We use data gathered from a large multinational survey, where analysis uses separate logistic regression models in each of nine country-specific data sets. In these data, applying multiple imputation by chained equations to the individual scale items is computationally infeasible. We propose an adaptation of multiple imputation by chained equations which imputes the individual scale items but reduces the number of variables in the imputation models by replacing most scale items with scale summary scores. We evaluate the feasibility of the proposed approach and compare it with a complete case analysis. We perform a simulation study to compare the proposed method with alternative approaches: we do this in a simplified setting to allow comparison with the full imputation model. RESULTS: For the case study, the proposed approach reduces the size of the prediction models from 134 predictors to a maximum of 72 and makes multiple imputation by chained equations computationally feasible. Distributions of imputed data are seen to be consistent with observed data. Results from the regression analysis with multiple imputation are similar to, but more precise than, results for complete case analysis; for the same regression models a 39% reduction in the standard error is observed. The simulation shows that our proposed method can perform comparably against the alternatives. CONCLUSIONS: By substantially reducing imputation model sizes, our adaptation makes multiple imputation feasible for large scale survey data with multiple multi-item scales. For the data considered, analysis of the multiply imputed data shows greater power and efficiency than complete case analysis. The adaptation of multiple imputation makes better use of available data and can yield substantively different results from simpler techniques. PMID- 26809814 TI - Troubling news from Asia about treating enteric fever: a coming storm. PMID- 26809813 TI - Gatifloxacin versus ceftriaxone for uncomplicated enteric fever in Nepal: an open label, two-centre, randomised controlled trial. AB - BACKGROUND: Because treatment with third-generation cephalosporins is associated with slow clinical improvement and high relapse burden for enteric fever, whereas the fluoroquinolone gatifloxacin is associated with rapid fever clearance and low relapse burden, we postulated that gatifloxacin would be superior to the cephalosporin ceftriaxone in treating enteric fever. METHODS: We did an open label, randomised, controlled, superiority trial at two hospitals in the Kathmandu valley, Nepal. Eligible participants were children (aged 2-13 years) and adult (aged 14-45 years) with criteria for suspected enteric fever (body temperature >=38.0 degrees C for >=4 days without a focus of infection). We randomly assigned eligible patients (1:1) without stratification to 7 days of either oral gatifloxacin (10 mg/kg per day) or intravenous ceftriaxone (60 mg/kg up to 2 g per day for patients aged 2-13 years, or 2 g per day for patients aged >=14 years). The randomisation list was computer-generated using blocks of four and six. The primary outcome was a composite of treatment failure, defined as the occurrence of at least one of the following: fever clearance time of more than 7 days after treatment initiation; the need for rescue treatment on day 8; microbiological failure (ie, blood cultures positive for Salmonella enterica serotype Typhi, or Paratyphi A, B, or C) on day 8; or relapse or disease-related complications within 28 days of treatment initiation. We did the analyses in the modified intention-to-treat population, and subpopulations with either confirmed blood-culture positivity, or blood-culture negativity. The trial was powered to detect an increase of 20% in the risk of failure. This trial was registered at ClinicalTrials.gov, number NCT01421693, and is now closed. FINDINGS: Between Sept 18, 2011, and July 14, 2014, we screened 725 patients for eligibility. On July 14, 2014, the trial was stopped early by the data safety and monitoring board because S Typhi strains with high-level resistance to ciprofloxacin and gatifloxacin had emerged. At this point, 239 were in the modified intention-to treat population (120 assigned to gatifloxacin, 119 to ceftriaxone). 18 (15%) patients who received gatifloxacin had treatment failure, compared with 19 (16%) who received ceftriaxone (hazard ratio [HR] 1.04 [95% CI 0.55-1.98]; p=0.91). In the culture-confirmed population, 16 (26%) of 62 patients who received gatifloxacin failed treatment, compared with four (7%) of 54 who received ceftriaxone (HR 0.24 [95% CI 0.08-0.73]; p=0.01). Treatment failure was associated with the emergence of S Typhi exhibiting resistance against fluoroquinolones, requiring the trial to be stopped. By contrast, in patients with a negative blood culture, only two (3%) of 58 who received gatifloxacin failed treatment versus 15 (23%) of 65 who received ceftriaxone (HR 7.50 [95% CI 1.71-32.80]; p=0.01). A similar number of non-serious adverse events occurred in each treatment group, and no serious events were reported. INTERPRETATION: Our results suggest that fluoroquinolones should no longer be used for treatment of enteric fever in Nepal. Additionally, under our study conditions, ceftriaxone was suboptimum in a high proportion of patients with culture-negative enteric fever. Since antimicrobials, specifically fluoroquinolones, are one of the only routinely used control measures for enteric fever, the assessment of novel diagnostics, new treatment options, and use of existing vaccines and development of next-generation vaccines are now a high priority. FUNDING: Wellcome Trust and Li Ka Shing Foundation. PMID- 26809815 TI - Subacute sclerosing panencephalitis in pregnancy. AB - We present a case of subacute sclerosing panencephalitis that developed in a previously healthy 29-year-old pregnant woman who had returned from a trip to rural India shortly before the onset of symptoms. She was admitted to hospital at 27 weeks' gestation with a history of cognitive decline and difficulty completing simple tasks. She had no clinical signs of infection. The working diagnosis was autoimmune encephalitis, although extensive investigations did not lead to a final classifying diagnosis. The patient became comatose and developed hypertension, and an emergency caesarean section was done at 31 weeks to deliver the child, who seemed healthy. The patient died about 6 weeks after the onset of symptoms. The patient was found to have had subacute sclerosing panencephalitis at autopsy. In this Grand Round, we review the clinical features and treatment of subacute sclerosing panencephalitis, and the epidemiological and public health aspects of the case. PMID- 26809817 TI - How much more malaria could be prevented? PMID- 26809816 TI - Potential for reduction of burden and local elimination of malaria by reducing Plasmodium falciparum malaria transmission: a mathematical modelling study. AB - BACKGROUND: Rapid declines in malaria prevalence, cases, and deaths have been achieved globally during the past 15 years because of improved access to first line treatment and vector control. We aimed to assess the intervention coverage needed to achieve further gains over the next 15 years. METHODS: We used a mathematical model of the transmission of Plasmodium falciparum malaria to explore the potential effect on case incidence and malaria mortality rates from 2015 to 2030 of five different intervention scenarios: remaining at the intervention coverage levels of 2011-13 (Sustain), for which coverage comprises vector control and access to treatment; two scenarios of increased coverage to 80% (Accelerate 1) and 90% (Accelerate 2), with a switch from quinine to injectable artesunate for management of severe disease and seasonal malaria chemoprevention where recommended for both Accelerate scenarios, and rectal artesunate for pre-referral treatment at the community level added to Accelerate 2; a near-term innovation scenario (Innovate), which included longer-lasting insecticidal nets and expansion of seasonal malaria chemoprevention; and a reduction in coverage to 2006-08 levels (Reverse). We did the model simulations at the first administrative level (ie, state or province) for the 80 countries with sustained stable malaria transmission in 2010, accounting for variations in baseline endemicity, seasonality in transmission, vector species, and existing intervention coverage. To calculate the cases and deaths averted, we compared the total number of each under the five scenarios between 2015 and 2030 with the predicted number in 2015, accounting for population growth. FINDINGS: With an increase to 80% coverage, we predicted a reduction in case incidence of 21% (95% credible intervals [CrI] 19-29) and a reduction in mortality rates of 40% (27-61) by 2030 compared with 2015 levels. Acceleration to 90% coverage and expansion of treatment at the community level was predicted to reduce case incidence by 59% (Crl 56-64) and mortality rates by 74% (67-82); with additional near-term innovation, incidence was predicted to decline by 74% (70-77) and mortality rates by 81% (76-87). These scenarios were predicted to lead to local elimination in 13 countries under the Accelerate 1 scenario, 20 under Accelerate 2, and 22 under Innovate by 2030, reducing the proportion of the population living in at-risk areas by 36% if elimination is defined at the first administrative unit. However, failing to maintain coverage levels of 2011-13 is predicted to raise case incidence by 76% (Crl 71-80) and mortality rates by 46% (39-51) by 2020. INTERPRETATION: Our findings show that decreases in malaria transmission and burden can be accelerated over the next 15 years if the coverage of key interventions is increased. FUNDING: UK Medical Research Council, UK Department for International Development, the Bill & Melinda Gates Foundation, the Swiss Development Agency, and the US Agency for International Development. PMID- 26809818 TI - Expression, purification and biological characterization of the extracellular domain of CD40 from Pichia pastoris. AB - BACKGROUND: CD40, also called Bp50, is a novel member of the TNF receptor superfamily. Based on its important role in multiple physiological and pathological processes, the CD40 signaling pathway has become a vital target for treating transplantation, autoimmune diseases and cancers. This study generated a protein fragment that disrupts this signaling pathway. RESULTS: A DNA fragment encoding the extracellular domain of CD40 (CD40-N) has been codon-optimized and cloned into pPIC9K to create a Pichia pastoris expression and secretion strain. SDS-PAGE and Western blotting assays using the culture media from methanol induced expression strains showed that recombinant CD40-N, a 27 kDa glycosylated protein, was secreted into the culture broth. The recombinant protein was purified to more than 90 % using Sephadex G-50 size-exclusion chromatography and Q Sepharose Fast Flow ion exchange. Finally, 120 mg of the protein was obtained at a relatively high purity from 3 l supernatant. Binding assay (ITC200 assay) shown the direct interaction of CD40-N and CD40 agonist antibody (G28-5). The bioactivity of recombinant CD40-N was confirmed by its ability to disrupt non canonical NF-kappaB signaling activated by CD40 agonist antibody or CD40 ligand and to inhibit ant-CD40 agonist antibody-induced TNF-alpha expression in BJAB cells in vitro. In addition, our data indicate that the protein has curative potential in treating dextran sulfate sodium (DSS)-induced colitis in vivo. CONCLUSIONS: The results show that the experimental procedure we have developed using P. pastoris can be used to produce large amounts of active CD40-N for research and industrial purposes. The protein fragment we have acquired has potential to be used in research or even treating inflammation diseases such as colitis. PMID- 26809820 TI - [Qualified biobanks are essential for successful biomedical research]. PMID- 26809819 TI - Diarrhoeagenic Escherichia coli in mother-child Pairs in Ile-Ife, South Western Nigeria. AB - BACKGROUND: Diarrhoeagenic Escherichia coli (DEC) pathotypes are among the most common bacterial causes of morbidity and mortality in young children. These pathogens are not sought routinely and capacity for their detection is limited in Africa. We investigated the distribution and dissemination of DEC in 126 children paired with their mothers in a Nigerian community. METHODS: A total of 861 E. coli were isolated from 126 children with diarrhoea and their mothers. Antimicrobial susceptibility of each isolate was determined by Kirby-Bauer disc diffusion technique. All the isolates were screened for DEC markers by multiplex PCR. Genetic relatedness of DEC strains was determined by flagellin typing and Insertion element 3 (IS3)-based PCR. RESULTS: DEC were identified from 35.7% of individuals with the most common pathotype being shiga toxin-producing E. coli (42, 16.7%). Identical pathotypes were found in 13 (10.3%) of the mother-child pairs and in three of these strains from mothers and their children showed identical genetic signatures. Over 90% of DEC isolates were resistant to ampicillin, sulphonamide, tetracycline, streptomycin or trimethoprim, but only 9 (7.2%) were ciprofloxacin resistant CONCLUSION: The data suggest that healthy mothers are asymptomatic reservoirs of multiply-resistant strains that are pathogenic in their children and there are instances in which identical strains are found in mother-child pairs. PMID- 26809821 TI - [The biobank of the German National Cohort as a resource for epidemiologic research]. AB - BACKGROUND: The linkage of high-quality biosamples with detailed data from medical examinations, questionnaires and interviews offers great opportunities for research. This is particularly true for large-scale prospective epidemiological studies with long observation periods, like the German National Cohort (GNC). AIM: The modalities of collecting, processing and storing biosamples of high quality and with a high throughput, as well as ethical aspects are described using the GNC as an example. MATERIAL AND METHODS: For the GNC, 200,000 randomly selected adults will be recruited by 18 study centres and will be followed up for 20-30 years. In addition to the extensive basic examination protocol, followed by reassessment examinations and follow-up questionnaires, the biorepository is a cornerstone of the GNC. RESULTS: The GNC biorepository will comprise more than 20 million aliquots of plasma, serum, erythrocytes, lymphocytes, urine, saliva, nasal swabs and stool. Preanalytics and aliquoting are performed locally in the study centres and are highly standardised and extensively automated. All samples are stored at - 80 and - 180 degrees C, respectively. A laboratory information system documents all processing steps and storage locations. Access to data and biosamples will be granted to researchers within and outside Germany after completion of the baseline recruitment (i.e. from 2018 onwards). DISCUSSION: Experience with already existing epidemiological biobanks shows impressive results, especially with regard to genetic research, as well as post-genomics (e.g. transcriptomics, metabolomics, epigenomics). Previous success stories explain the strongly increased demand for data and biosamples from the population. Thus the GNC will provide an important resource for biomedical research in the future. PMID- 26809822 TI - [Current modalities and concepts on access and use of biospecimen samples and associated data for research from human biobanks]. AB - It is accepted worldwide that biospecimen and data sharing (BDS) play an essential role for the future of medical research to improve diagnostics and prognostics, e.g. by validated biomarkers. BDS is also pivotal to the development of new therapeutic treatments and for the improvement of population health. Human biobanks can generate an added value to this need by providing biospecimens and/or associated data to researchers. An inspection of several examples of epidemiological as well as clinical/disease-oriented biobanks in Germany shows that best practice procedures (BPP) that are internationally agreed on are being installed for biospecimen and/or data access. In general, fair access is aimed at requiring a written application by the requesting scientist, which is then peer reviewed for scientific and ethical validity by the Biobank. Applied BPP take into account (i) patient education/agreement according to the informed consent model, (ii) privacy protection, (iii) intellectual property rights, the (iv) notification obligation of health-related findings (including incidental findings), the (v) use of material (MTA) and data transfer agreements (DTA) for mutual legal security, the avoidance of conflicts of interests, as well as for cost recovery/fee for service as a basis for sustainability of the biobank. BPP are rooted in the self-regulation efforts of life sciences and are supported by parent ethics committees in Germany. Central biobank registries displaying aggregated information on biospecimens stored and the research foci constitute an important tool to make biobanks that are scattered across the country visible to each other, and, can thus promote access to hitherto unknown biospecimen and data resources. PMID- 26809823 TI - [Connecting biobanks of large European cohorts (EU Project BBMRI-LPC)]. AB - BACKGROUND: In addition to the Biobanking and BioMolecular resources Research Initiative (BBMRI), which is establishing a European research infrastructure for biobanks, a network for large European prospective cohorts (LPC) is being built to facilitate transnational research into important groups of diseases and health care. One instrument for this is the database "LPC Catalogue," which supports access to the biomaterials of the participating cohorts. OBJECTIVES: To present the LPC Catalogue as a relevant tool for connecting European biobanks. In addition, the LPC Catalogue has been extended to establish compatibility with existing Minimum Information About Biobank data Sharing (MIABIS) and to allow for more detailed search requests. This article describes the LPC Catalogue, its organizational and technical structure, and the aforementioned extensions. MATERIALS AND METHODS: The LPC Catalogue provides a structured overview of the participating LPCs. It offers various retrieval possibilities and a search function. To support more detailed search requests, a new module has been developed, called a "data cube". The provision of data by the cohorts is being supported by a "connector" component. RESULTS: The LPC Catalogue contains data on 22 cohorts and more than 3.8 million biosamples. At present, data on the biosamples of three cohorts have been acquired for the "cube," which is continuously being expanded. In the BBMRI-LPC, tendering for scientific projects using the data and samples of the participating cohorts is currently being carried out. In this context, several proposals have already been approved. CONCLUSIONS: The LPC Catalogue is supporting transnational access to biosamples. A comparison with existing solutions illustrates the relevance of its functionality. PMID- 26809824 TI - French drug trial protocol fails to answer key questions. PMID- 26809825 TI - Posttraumatic Growth Among Japanese Parentally Bereaved Adolescents: A Web-Based Survey. AB - OBJECTIVE: The aim of this study was to explore the factors associated with posttraumatic growth (PTG) among adolescents bereaved owing to parental cancer in Japan. METHODS: An anonymous cross-sectional Web-based survey was conducted, enrolling adolescents bereaved because of parental cancer in the previous 5 years. Posttraumatic growth, number of social support members, support from medical staff, and behaviors after bereavement were measured. Multiple linear regression was performed to explore the association between total PTG score and possible related factors. RESULTS: We assessed 57 participants in this study. Mean age was 19.3 (standard deviation [SD] = 2.0) years, and most participants were female (75.4%). Mean total score of the Japanese version of the PTG inventory was 43.0 (SD = 25.6). Participants' mean number of social support members was 2.1 (SD = 1.3), and these support members were the surviving parent (66.7%), friends (38.6%), and siblings (36.8%). The multiple linear regression model explained 45% of the variance in PTG. In this model, the following 3 behaviors after bereavement were associated with PTG: "putting palms together in front of a parent's picture or an altar" (beta = .36, P = .006), "visiting a parent's grave" (beta = .29, P = .03), and "having fun with friends" (beta = .25, P = .04). CONCLUSION: Parentally bereaved adolescents in Japan experience PTG. Specific behaviors after bereavements might be recommended for PTG among Japanese adolescents bereaved because of parental cancer. PMID- 26809826 TI - Hope, Symptoms, and Palliative Care. AB - BACKGROUND: Hope is important to patients with cancer. Identifying factors that influence hope is important. Anxiety, depression, fatigue, and pain are reported to impair hope. The objective of this study was to determine whether age, gender, marital status, duration of cancer, symptoms, or symptom burden measured by the sum of severity scores on the Edmonton Symptom Assessment Scale (ESAS) correlated with hope measured by the Herth Hope Index (HHI). METHODS: Patients with advanced cancer in a palliative care unit participated. Demographics including age, gender, marital status, cancer site, and duration of cancer were collected. Individuals completed the ESAS and HHI. Spearman correlation and linear regression were used to assess associations adjusting for gender (male vs female), age (< 65 vs >= 65 years), marital status (married or living with a partner vs other), and duration of cancer (<= 12 vs > 12 months). RESULTS: One hundred and ninety-seven were participated in the study, of which 55% were female with a mean age of 61 years (standard deviation 11). Hope was not associated with gender, age, marital status, or duration of cancer. In univariable analysis, hope inversely correlated with ESAS score (-0.28), lack of appetite (-0.22), shortness of breath (-0.17), depression (-0.39), anxiety (-0.32), and lack of well-being ( 0.33); only depression was clinically relevant. In multivariable analysis, total symptom burden weakly correlated with hope; only depression remained clinically significant. DISCUSSION: This study found correlation between symptom burden and hope was not clinically relevant but was so for depression. CONCLUSION: Among 9 ESAS symptoms, only depression had a clinically relevant correlation with hope. PMID- 26809827 TI - Exploring Sensory Experiences and Personalization in an Inpatient Residential Hospice Setting. AB - Residential hospices are often purpose-built to enhance the experience of patients and families. However, there has been relatively little research on ambient and sensory experiences of patients and families. This study explored the ambient and sensory experience of residents and families in a residential hospice. Hospice users participated in personalizing environments and experiences, adapting and developing rituals, and enjoying the experience (including smells and sounds) of communal spaces and private rooms. Opportunity for developing new rituals, in particular, suggests an environment supportive of sense of control, social support, and positive distractors. The design of an inpatient hospice can offer a platform through which to support the delivery of flexible care practices, providing opportunities for personal expression, shared experiences, and the maintenance or development of rituals. PMID- 26809828 TI - Trends of imported malaria in China 2010-2014: analysis of surveillance data. AB - BACKGROUND: To describe the epidemiologic profile and trends of imported malaria, and to identify the populations at risk of malaria in China during 2010-2014. METHODS: This is a descriptive analysis of laboratory confirmed malaria cases during 2010-2014. Data were obtained from surveillance reports in the China Information System for Disease Control and Prevention (CISDCP). The distribution of imported malaria cases over the years was analysed with X(2) for trend analysis test. All important demographic and epidemiologic variables of imported malaria cases were analysed. RESULTS: Malaria incidence in general reduced greatly in China, while the proportion of Plasmodium falciparum increased threefold from 0.08 to 0.21 per 100,000 population during the period 2010-2014. Of a total 17,725 malaria cases reported during the study period, 11,331 (64%) were imported malaria and included an increasing trend: 292 (6%), 2103 (63%), 2151 (84%), 3881 (96%), 2904 (97%), respectively, (X(2) = 2110.70, p < 0.01). The majority of malaria cases (imported and autochthonous) were adult (16,540, 93%), male (15,643, 88%), and farming as an occupation (11,808, 66%). Some 3027 (94%) of imported malaria cases had labour-related travel history during the study period; 90% (6340/7034) of P. falciparum infections were imported into China from Africa, while 77% of Plasmodium vivax infections (2440/3183) originated from Asia. CONCLUSIONS: Malaria elimination in China faces the challenge of imported malaria, especially imported P. falciparum. Malaria prevention activities should target exported labour groups given the increasing number of workers returning from overseas. PMID- 26809830 TI - Female behaviour and the interaction of male and female genital traits mediate sperm transfer during mating. AB - Natural selection and post-copulatory sexual selection, including sexual conflict, contribute to genital diversification. Fundamental first steps in understanding how these processes shape the evolution of specific genital traits are to determine their function experimentally and to understand the interactions between female and male genitalia during copulation. Our experimental manipulations of male and female genitalia in red-sided garter snakes (Thamnophis sirtalis parietalis) reveal that copulation duration and copulatory plug deposition, as well as total and oviductal/vaginal sperm counts, are influenced by the interaction between male and female genital traits and female behaviour during copulation. By mating females with anesthetized cloacae to males with spine-ablated hemipenes using a fully factorial design, we identified significant female-male copulatory trait interactions and found that females prevent sperm from entering their oviducts by contracting their vaginal pouch. Furthermore, these muscular contractions limit copulatory plug size, whereas the basal spine of the male hemipene aids in sperm and plug transfer. Our results are consistent with a role of sexual conflict in mating interactions and highlight the evolutionary importance of female resistance to reproductive outcomes. PMID- 26809832 TI - Percutaneous perirenal thrombin injection for the treatment of acute hemorrhage after renal biopsy. AB - Percutaneous renal biopsy is a valuable diagnostic approach. While commonly safe, it is not without risk and the most feared vascular complications include hemorrhage, pseudoaneurysm, and arteriovenous fistula formation. We report a case of acute hemorrhage after renal biopsy that was immediately identified by ultrasonography and successfully treated with percutaneous perirenal thrombin injection. This technique may prove a useful addition to the armamentarium of any operator performing renal biopsies. PMID- 26809831 TI - Severe symptomatic intracranial internal carotid artery stenosis treated with intracranial stenting: a single center study with 58 patients. AB - PURPOSE: We aimed to investigate the safety and effectiveness of intracranial stenting in a population with severe (>= 70%) symptomatic intracranial internal carotid artery (ICA) atherosclerotic stenosis. METHODS: Fifty-eight patients with severe intracranial ICA atherosclerotic stenosis were prospectively enrolled. The baseline data, cerebral angiography, success rate, perioperative complications, clinical and imaging follow-up were prospectively analyzed. RESULTS: All patients had successful intracranial stenting (100%), and the mean degree of stenosis was improved from 84.3% +/- 7.5% to 23.5% +/- 5.1% after the stent procedure. During the 30-day perioperative period, only one patient (1.7%) had ischemic stroke. Seven patients (12.1%) had headache and dysphoria. Thirty-six patients (62.1%) had clinical follow-up for 6-68 months after stenting. Five female patients (13.9%) had ipsilateral stroke including one death, but no disabling stroke, while three other patients (8.3%) had ipsilateral temporary ischemic attack (TIA). The recurrent stroke rate was higher in patients presenting with stroke (4/17, 23.5%) than in patients presenting with TIA (1/19, 5.3%), with no statistical significance (P = 0.33). Thirteen patients (22.4%) had imaging follow up of 5-12 months following stenting, five of whom (38.5%) had in-stent restenosis. CONCLUSION: Intracranial stenting for patients with intracranial ICA atherosclerotic stenosis has a low perioperative stroke rate and decent outcome on long-term follow-up, despite a relatively high in-stent restenosis rate. PMID- 26809833 TI - Significant enhancement of gas uptake capacity and selectivity via the judicious increase of open metal sites and Lewis basic sites within two polyhedron-based metal-organic frameworks. AB - Two new isomorphous polyhedron-based MOFs ( and ), with dual functionalities of OMSs and LBSs, have been synthesized by using the SBB strategy. By judiciously avoiding the DABCO axial ligand, possesses more OMSs than , and exhibits a significant enhancement of CO2 uptake capacity 210 versus 162 cm(3) g(-1) for at 273 K under 1 bar. PMID- 26809834 TI - Haemophilia and low bone mass. Ok, but what about fracture risk? PMID- 26809835 TI - Overcoming the diagnostic and monitoring challenges for very rare bleeding disorders in the US: the potential benefits of a centralized laboratory. PMID- 26809836 TI - Hydrogenotrophic denitrification process efficiency and the number of denitrifying bacteria (MPN) in the sequencing batch biofilm reactor (SBBR) with platinum and carbon anodes. AB - This work reports on the effect of electric current density and anode material (platinum, carbon) on the concentration of oxidized and mineral forms of nitrogen, on physical parameters (pH, redox potential, electrical conductivity) and the number of denitrifying bacteria in the biofilm (MPN). Experiments were conducted under anaerobic conditions without and with the flow of electric current (with density of 79 mA . m(-2) and 132 mA . m(-2)). Results obtained in the study enabled concluding that increasing density of electric current caused a decreasing concentration of nitrate in the reactor with platinum anode (R1) and carbon anode (R2). Its concentration depended on anode material. The highest hydrogenotrophic denitrification efficiency was achieved in R2 in which the process was aided by inorganic carbon (CO2) that originated from carbon anode oxidation and the electrical conductivity of wastewater increased as a result of the presence of HCO3(-) and CO3(2-) ions. Strong oxidizing properties of the platinum anode (R1) prevented the accumulation of adverse forms of nitrogen, including nitrite and ammonia. The increase in electric current density affected also a lower number of denitrifying bacteria (MPN) in the biofilm in both reactors (R1 and R2). Metal oxides accumulated on the surface of the cathode had a toxic effect upon microorganisms and impaired the production of a hydrogen donor. PMID- 26809837 TI - Changing relationships between smoking and psychiatric disorders across twentieth century birth cohorts: clinical and research implications. AB - As the risks of tobacco use become recognized and smoking becomes stigmatized, new smokers may be increasingly driven to smoke by biological or genetic vulnerabilities rather than social desirability. Given that genetic risk for deviant proneness is shared across other psychiatric and addictive disorders, we predicted that as rates of smoking decreased through the latter half of the twentieth century, associations between smoking and psychopathology would increase. Participants (N=25 412) from a large US study-the National Epidemiologic Survey on Alcohol and Related Conditions, NESARC-were interviewed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule - DSM-IV Version (AUDADIS-IV) and classified into one of five birth cohort decades (1940s to 1980s) and three smoking history (nonsmokers, never-dependent smokers and ever-dependent smokers) groups. We found that the prevalence of smoking decreased across the five birth cohorts, but associations of smoking with drug and AUDs, attention-deficit hyperactivity disorder, bipolar disorder and antisocial personality disorder, each increased monotonically in more recently born cohorts, even after adjusting for concurrent demographic and socioeconomic changes. For drug and AUDs, increases were observed among smokers both with and without a history of nicotine dependence; for other outcomes, increases were entirely driven by nicotine-dependent smokers. Findings suggest that smokers in more recent cohorts have disproportionately high psychiatric vulnerability, and may benefit from greater mental health screenings. Differentiating between casual and dependent smokers may further help prioritize those at greatest risk. Researchers should also be aware of potential variation in psychiatric comorbidity based on cohort of birth when defining groups of smokers, to minimize confounding. PMID- 26809838 TI - Revisiting adult neurogenesis and the role of erythropoietin for neuronal and oligodendroglial differentiation in the hippocampus. AB - Recombinant human erythropoietin (EPO) improves cognitive performance in neuropsychiatric diseases ranging from schizophrenia and multiple sclerosis to major depression and bipolar disease. This consistent EPO effect on cognition is independent of its role in hematopoiesis. The cellular mechanisms of action in brain, however, have remained unclear. Here we studied healthy young mice and observed that 3-week EPO administration was associated with an increased number of pyramidal neurons and oligodendrocytes in the hippocampus of ~20%. Under constant cognitive challenge, neuron numbers remained elevated until >6 months of age. Surprisingly, this increase occurred in absence of altered cell proliferation or apoptosis. After feeding a 15N-leucine diet, we used nanoscopic secondary ion mass spectrometry, and found that in EPO-treated mice, an equivalent number of neurons was defined by elevated 15N-leucine incorporation. In EPO-treated NG2-Cre-ERT2 mice, we confirmed enhanced differentiation of preexisting oligodendrocyte precursors in the absence of elevated DNA synthesis. A corresponding analysis of the neuronal lineage awaits the identification of suitable neuronal markers. In cultured neurospheres, EPO reduced Sox9 and stimulated miR124, associated with advanced neuronal differentiation. We are discussing a resulting working model in which EPO drives the differentiation of non-dividing precursors in both (NG2+) oligodendroglial and neuronal lineages. As endogenous EPO expression is induced by brain injury, such a mechanism of adult neurogenesis may be relevant for central nervous system regeneration. PMID- 26809840 TI - In-depth neuropharmacokinetic analysis of antipsychotics based on a novel approach to estimate unbound target-site concentration in CNS regions: link to spatial receptor occupancy. AB - The current study provides a novel in-depth assessment of the extent of antipsychotic drugs transport across the blood-brain barrier (BBB) into various brain regions, as well as across the blood-spinal cord barrier (BSCB) and the blood-cerebrospinal fluid barrier (BCSFB). This is combined with an estimation of cellular barrier transport and a systematic evaluation of nonspecific brain tissue binding. The study is based on the new Combinatory Mapping Approach (CMA), here further developed for the assessment of unbound drug neuropharmacokinetics in regions of interest (ROI), referred as CMA-ROI. We show that differences exist between regions in both BBB transport and in brain tissue binding. The most dramatic spatial differences in BBB transport were found for the P-glycoprotein substrates risperidone (5.4-fold) and paliperidone (4-fold). A higher level of transporter-mediated protection was observed in the cerebellum compared with other brain regions with a more pronounced efflux for quetiapine, risperidone and paliperidone. The highest BBB penetration was documented in the frontal cortex, striatum and hippocampus (haloperidol, olanzapine), indicating potential influx mechanisms. BSCB transport was in general characterized by more efficient efflux compared with the brain regions. Regional tissue binding was significantly different for haloperidol, clozapine, risperidone and quetiapine (maximally 1.9 fold). Spatial differences in local unbound concentrations were found to significantly influence cortical 5-HT2A receptor occupancy for risperidone and olanzapine. In conclusion, the observed regional differences in BBB penetration may potentially be important factors contributing to variations in therapeutic effect and side effect profiles among antipsychotic drugs. PMID- 26809839 TI - Mast cells' involvement in inflammation pathways linked to depression: evidence in mastocytosis. AB - Converging sources of evidence point to a role for inflammation in the development of depression, fatigue and cognitive dysfunction. More precisely, the tryptophan (TRP) catabolism is thought to play a major role in inflammation induced depression. Mastocytosis is a rare disease in which chronic symptoms, including depression, are related to mast cell accumulation and activation. Our objectives were to study the correlations between neuropsychiatric features and the TRP catabolism pathway in mastocytosis in order to demonstrate mast cells' potential involvement in inflammation-induced depression. Fifty-four patients with mastocytosis and a mean age of 50.1 years were enrolled in the study and compared healthy age-matched controls. Depression and stress were evaluated with the Beck Depression Inventory revised and the Perceived Stress Scale. All patients had measurements of TRP, serotonin (5-HT), kynurenine (KYN), indoleamine 2,3-dioxygenase 1 (IDO1) activity (ratio KYN/TRP), kynurenic acid (KA) and quinolinic acid (QA). Patients displayed significantly lower levels of TRP and 5 HT without hypoalbuminemia or malabsorption, higher IDO1 activity, and higher levels of KA and QA, with an imbalance towards the latter. High perceived stress and high depression scores were associated with low TRP and high IDO1 activity. In conclusion, TRP metabolism is altered in mastocytosis and correlates with perceived stress and depression, demonstrating mast cells' involvement in inflammation pathways linked to depression. PMID- 26809841 TI - Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N=112 151) and 24 GWAS consortia. AB - Causes of the well-documented association between low levels of cognitive functioning and many adverse neuropsychiatric outcomes, poorer physical health and earlier death remain unknown. We used linkage disequilibrium regression and polygenic profile scoring to test for shared genetic aetiology between cognitive functions and neuropsychiatric disorders and physical health. Using information provided by many published genome-wide association study consortia, we created polygenic profile scores for 24 vascular-metabolic, neuropsychiatric, physiological-anthropometric and cognitive traits in the participants of UK Biobank, a very large population-based sample (N=112 151). Pleiotropy between cognitive and health traits was quantified by deriving genetic correlations using summary genome-wide association study statistics and to the method of linkage disequilibrium score regression. Substantial and significant genetic correlations were observed between cognitive test scores in the UK Biobank sample and many of the mental and physical health-related traits and disorders assessed here. In addition, highly significant associations were observed between the cognitive test scores in the UK Biobank sample and many polygenic profile scores, including coronary artery disease, stroke, Alzheimer's disease, schizophrenia, autism, major depressive disorder, body mass index, intracranial volume, infant head circumference and childhood cognitive ability. Where disease diagnosis was available for UK Biobank participants, we were able to show that these results were not confounded by those who had the relevant disease. These findings indicate that a substantial level of pleiotropy exists between cognitive abilities and many human mental and physical health disorders and traits and that it can be used to predict phenotypic variance across samples. PMID- 26809842 TI - Metformin treatment of antipsychotic-induced dyslipidemia: an analysis of two randomized, placebo-controlled trials. AB - Dyslipidemia is one of the most common adverse effects in schizophrenia patients treated with antipsychotics. However, there are no established effective treatments. In this study, data were pooled from two randomized, placebo controlled trials, which were originally designed to examine the efficacy of metformin in treating antipsychotic-induced weight gain and other metabolic abnormalities. In total, 201 schizophrenia patients with dyslipidemia after being treated with an antipsychotic were assigned to take 1000 mg day-1 metformin (n=103) or placebo (n=98) for 24 weeks, with evaluation at baseline, week 12 and week 24. The primary outcome was the low-density lipoprotein cholesterol (LDL-C) levels. After metformin treatment, the mean difference in the LDL-C value between metformin treatment and placebo was from 0.16 mmol l-1 at baseline to -0.86 mmol l-1 at the end of week 24, decreased by 1.02 mmol l-1 (P<0.0001); and 25.3% of patients in the metformin group had LDL-C >=3.37 mmol l-1, which is significantly <64.8% in the placebo group (P<0.001) at week 24. Compared with the placebo, metformin treatment also have a significant effect on reducing weight, body mass index, insulin, insulin resistance index, total cholesterol and triglyceride, and increasing high-density lipoprotein cholesterol. The treatment effects on weight and insulin resistance appeared at week 12 and further improved at week 24, but the effects on improving dyslipidemia only significantly occurred at the end of week 24. We found that metformin treatment was effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effects improving antipsychotic-induced insulin resistance appeared earlier than the reducing dyslipidemia. PMID- 26809843 TI - Understanding how non-coding genomic polymorphisms affect gene expression. AB - The NIH Common Fund GTEx project is designed to serve as a data and post-mortem tissue resource to the research community. The project is testing the role of genomic variation in altering gene expression across a wide array of tissues in a large number of human post-mortem donors. Both data and tissue samples are available to the research community for additional studies. PMID- 26809844 TI - The effects of stress on brain and adrenal stem cells. AB - The brain and adrenal are critical control centers that maintain body homeostasis under basal and stress conditions, and orchestrate the body's response to stress. It is noteworthy that patients with stress-related disorders exhibit increased vulnerability to mental illness, even years after the stress experience, which is able to generate long-term changes in the brain's architecture and function. High levels of glucocorticoids produced by the adrenal cortex of the stressed subject reduce neurogenesis, which contributes to the development of depression. In support of the brain-adrenal connection in stress, many (but not all) depressed patients have alterations in the components of the limbic-hypothalamic-pituitary adrenal (LHPA) axis, with enlarged adrenal cortex and increased glucocorticoid levels. Other psychiatric disorders, such as post-traumatic stress disorder, bipolar disorder and depression, are also associated with abnormalities in hippocampal volume and hippocampal function. In addition, hippocampal lesions impair the regulation of the LHPA axis in stress response. Our knowledge of the functional connection between stress, brain function and adrenal has been further expanded by two recent, independent papers that elucidate the effects of stress on brain and adrenal stem cells, showing similarities in the way that the progenitor populations of these organs behave under stress, and shedding more light into the potential cellular and molecular mechanisms involved in the adaptation of tissues to stress. PMID- 26809845 TI - Pulmonary metastasectomy from renal cell carcinoma including 3 cases with sarcomatoid component. AB - INTRODUCTION: Usefulness of complete metastasectomy against pulmonary metastases from renal cell carcinoma (RCC) is well known. We examined the efficacy of surgical resection of pulmonary metastases from RCC performed in Shikoku Cancer Center. METHOD: Between January 2004 and December 2014, 11 patients with pulmonary metastases from RCC underwent thoracic resection in our institution. We examined disease-free interval (DFI) and overall survival of these patients after pulmonary metastasectomy. RESULTS: Patients included 9 men and 2 women with a mean age of 63.2 years. The median number of metastases was 1 (range 1-6). Overall, 5 patients had a single metastasis (45.5%), 8 patients had unilateral metastases (72.7%), and 3 patients received immunotherapy or chemotherapy in the interval between radical nephrectomy and pulmonary metastasectomy. We performed complete pulmonary metastasectomy in these patients. The median observation period was 43 months (range 5-82), median DFI was 5 months (range 2-17), and 3 year overall survival rate was 86%. In the 3 patients who had primary or metastatic tumors with sarcomatoid (SA) component, their median DFI tended to be shorter than that of 8 patients without it (2 vs. 8 months, p = 0.07). CONCLUSION: The pulmonary metastasectomy for RCC is a treatment option, while the indication for RCC with SA component should be carefully considered. PMID- 26809848 TI - Silyllithium-Initiated Coupling of alpha-Ketoamides with tert Butanesulfinylimines for Stereoselective Synthesis of Enantioenriched alpha (Silyloxy)-beta-amino Amides. AB - A silyllithium-initiated coupling of alpha-ketoamides with tert butanesulfinylimines was developed for the efficient, stereoselective synthesis of enantioenriched alpha-(silyloxy)-beta-amino amides. Nucleophilic addition of silyllithium to alpha-ketoamides, followed by 1,2-Brook rearrangement, generates nucleophilic enolates, which are then intercepted by chiral imines to provide three-component coupling products. Use of alpha-ketoamides is critical for achieving high yields and diastereoselectivities in the resulting alpha-hydroxy beta-amino acid derivatives. PMID- 26809849 TI - Effect of Mailing Nicotine Patches on Tobacco Cessation Among Adult Smokers: A Randomized Clinical Trial. AB - IMPORTANCE: The efficacy of nicotine replacement therapy (NRT) is well demonstrated in clinical trials in which NRT is accompanied by behavioral support. Epidemiologic data, however, indicate that people using NRT are no more likely to successfully quit smoking than those who do not use NRT. OBJECTIVE: To evaluate the effect of mailing nicotine patches to smokers without behavioral support on quit success rates. DESIGN, SETTING, AND PARTICIPANTS: A single blinded, 2-group randomized clinical trial of adult smokers recruited across Canada by random-digit dialing of home and cell telephone numbers from June 4, 2012, through June 26, 2014. Follow-up was completed on January 5, 2015, and data were analyzed from May 24, 2015, through July 6, 2015. A total of 2093 individuals who smoked more than 10 cigarettes per day were interviewed at baseline and asked if they would be hypothetically interested in receiving nicotine patches by mail to quit smoking. Those who were interested and deemed eligible to participate (no contraindications to NRT) were randomized to the experimental group to be mailed a 5-week supply of nicotine patches or to a control group. Telephone follow-ups were conducted at 8 weeks and 6 months. INTERVENTIONS: Participants in the experimental group were sent a 5-week course of nicotine patches by expedited postal mail (3 weeks of step 1 [21 mg of nicotine], 1 week of step 2 [14 mg of nicotine], 1 week of step 3 [7 mg of nicotine], no behavioral support provided). Participants randomized to the control group were not offered the nicotine patches or any other intervention. MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day smoking abstinence at 6 months. RESULTS: Of the 2093 participants who were interviewed as part of the baseline survey (76.5% response rate), 1000 were found eligible for the trial and randomized to a group. Analyses were conducted on 500 participants in the experimental group (mean [SD] age, 48.0 [12.8] years; 255 female [51.0%]) and 499 in the control group (mean [SD] age, 49.7 [12.7] years; 256 female [51.3%]). Self reported abstinence rates were significantly higher among participants who were sent nicotine patches compared with the control group (30-day abstinence: 38 [7.6%] of 500 vs 15 [3.0%] of 499; odds ratio, 2.65; 95% CI, 1.44-4.89; P = .002). Usable saliva samples were returned by only 50.9% of the participants. Biochemically validated abstinence at 6 months was found in 14 (2.8%) of 500 participants in the experimental group vs 5 (1.0%) of 499 in the control group (odds ratio, 2.85; 95% CI, 1.02-7.96; P = .046). CONCLUSIONS AND RELEVANCE: The trial provides evidence of the effectiveness of mailed nicotine patches without behavioral support to promote tobacco cessation. The strength of these findings is tempered by the lack of biochemical validation for all participants. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01429129. PMID- 26809851 TI - Quantifying differences between conditions in single-case designs: Possible analysis and meta-analysis. AB - The current paper is a call for and illustration of a way of closing the gap between basic research and professional practice in the field of neurorehabilitation. Methodologically, single-case experimental designs and the guidelines created regarding their conduct are highlighted. Statistically, we review two data analytical options, namely (a) indices quantifying the difference between pairs of conditions in the same metric as the target behavior and (b) a formal statistical procedure offering a standardized overall quantification. The paper provides guidance in the analysis and suggests free software in order to illustrate, in the context of data from behavioral interventions with children with developmental disorders, that informative analyses are feasible. We also show how the results of individual studies can be made eligible for meta analyses, which are useful for establishing the evidence basis of interventions. Nevertheless, we also point at decisions that need to be made during the process of data analysis. PMID- 26809850 TI - Expectancy Effects on Conditioned Pain Modulation Are Not Influenced by Naloxone or Morphine. AB - BACKGROUND: Recent studies suggest that participant expectations influence pain ratings during conditioned pain modulation testing. The present study extends this work by examining expectancy effects among individuals with and without chronic back pain after administration of placebo, naloxone, or morphine. PURPOSE: This study aims to identify the influence of individual differences in expectancy on changes in heat pain ratings obtained before, during, and after a forearm ischemic pain stimulus. METHODS: Participants with chronic low back pain (n = 88) and healthy controls (n = 100) rated heat pain experience (i.e., "test stimulus") before, during, and after exposure to ischemic pain (i.e., "conditioning stimulus"). Prior to testing, participants indicated whether they anticipated that their heat pain would increase, decrease, or remain unchanged during ischemic pain. RESULTS: Analysis of the effects of expectancy (pain increase, decrease, or no change), drug (placebo, naloxone, or morphine), and group (back pain, healthy) on changes in heat pain revealed a significant main effect of expectancy (p = 0.001), but no other significant main effects or interactions. Follow-up analyses revealed that individuals who expected lower pain during ischemia reported significantly larger decreases in heat pain as compared with those who expected either no change (p = 0.004) or increased pain (p = 0.001). CONCLUSIONS: The present findings confirm that expectancy is an important contributor to conditioned pain modulation effects, and therefore significant caution is needed when interpreting findings that do not account for this individual difference. Opioid mechanisms do not appear to be involved in these expectancy effects. PMID- 26809852 TI - [Discussion paper on participation and participative methods in gerontology]. AB - The concept of "participation" and the demand for the use of "participative methods" in human, healthcare, nursing and gerontological research as well as the corresponding fields of practice are in great demand; however, the targets and organization of "participation" are not always sufficiently explicated. The working group on critical gerontology of the German Society of Gerontology and Geriatrics uses this phenomenon as an opportunity for positioning and develops a catalogue of criteria for reflection and assessment of participation of elderly people in science and practice, which can also be considered a stimulus for further discussions. PMID- 26809853 TI - [Depression in old age, part 1 : Origin, clinical symptoms, diagnosis and interaction between depression and dementia]. AB - Depression is one of the most frequent mental disorders in old age. A huge variety of very different causal factors can contribute to late life depression as a common final outcome. The pathogenic pathways of depression overlap with those of frequent somatic medical conditions, such as diabetes and ischemic heart disease. Age-specific modulations of symptom presentation are described in this article with special emphasis on subthreshold depression and the complex mutual relationship between depression and dementia is presented. PMID- 26809854 TI - (1)H NMR-based metabolomics of Daphnia magna responses after sub-lethal exposure to triclosan, carbamazepine and ibuprofen. AB - Pharmaceuticals and personal care products are a class of emerging contaminants that are present in wastewater effluents, surface water, and groundwater around the world. There is a need to determine rapid and reliable bioindicators of exposure and the toxic mode of action of these contaminants to aquatic organisms. (1)H nuclear magnetic resonance (NMR)-based metabolomics in combination with multivariate statistical analysis was used to determine the metabolic profile of Daphnia magna after exposure to a range of sub-lethal concentrations of triclosan (6.25-100MUg/L), carbamazepine (1.75-14mg/L) and ibuprofen (1.75-14mg/L) for 48h. Sub-lethal triclosan exposure suggested a general oxidative stress condition and the branched-chain amino acids, glutamine, glutamate, and methionine emerged as potential bioindicators. The aromatic amino acids, serine, glycine and alanine are potential bioindicators for sub-lethal carbamazepine exposure that may have altered energy metabolism. The potential bioindicators for sub-lethal ibuprofen exposure are serine, methionine, lysine, arginine and leucine, which showed a concentration-dependent response. The differences in the metabolic changes were related to the dissimilar modes of toxicity of triclosan, carbamazepine and ibuprofen. (1)H NMR-based metabolomics gave an improved understanding of how these emerging contaminants impact the keystone species D. magna. PMID- 26809856 TI - The savior of binge drinkers: Another liver tonic from a common vegetable? PMID- 26809858 TI - Laryngotracheobronchial anomalies in infants and the related risk factors of in hospital mortality. AB - BACKGROUND: Laryngotracheobronchial anomalies (LTBAs) may cause respiratory problems during early childhood, and increase the risk of hospitalization or mortality in diseased children. This study investigated the initial hospitalization age and risk factors for in-hospital mortality in infants diagnosed with LTBAs during their first 5 years of life. METHODS: Hospitalized infants diagnosed with LTBAs were retrieved from Taiwan's National Health Insurance Research Database from 2003 to 2005. Their medical claim data were traced up to 59 months of age. The age distribution of all LTBA cases was analyzed, and then the enrolled infants were grouped into two age groups. Hospitalization-related comorbidities and risk factors for in-hospital mortality were also analyzed. RESULTS: A total of 1272 LTBA cases were retrieved. Most of them (976, 76.7%) were initially hospitalized at an age of 0-3 months, and 47 infants (3.7%) died. These enrolled cases were grouped into early and late LTBA groups, with ages of 0-3 months and 4-11 months, respectively. Patients in the late LTBA group had significantly more acute airway infections/asthma and neurological diseases, more frequent hospitalizations, longer hospitalization stay, and higher in-hospital mortality than did the early LTBA group (p < 0.001). The adjusted odds ratios (aORs) for in-hospital mortality were significantly higher in the children aged 4-11 months [aOR = 2.50, 95% confidence intervals (CI): 1.36-4.60], or having perinatal disease (aOR = 2.00, 95% CI: 1.07-3.73), cardiovascular disease (aOR = 2.45, 95% CI: 1.30-4.60), other congenital anomalies (aOR = 2.42, 95% CI: 1.28-4.60), and neurological diseases (aOR = 2.32, 95% CI: 1.18-4.53). CONCLUSION: Most infants with LTBAs were initially diagnosed and hospitalized when they were aged 3 months or younger. The risk factors for in hospital mortality of the children with LTBAs included being diagnosed and treated at an age of 4 months and older, and the presence of perinatal disease, cardiovascular anomalies, other congenital anomalies, neurological diseases, and an age of 4 months and older. PMID- 26809857 TI - The impact of chronic carrier of hepatitis B virus on liver function in a 7-day ultramarathon race. AB - BACKGROUND: Several changes in physiological characteristics occur during long distance and 24-hour ultramarathons, including hyponatremia, skeletal muscle breakdown, plasma volume changes, iron depletion, anemia, and possible hepatic damage. The purpose of this study was to investigate the impact of hepatitis B virus (HBV) carrier status on liver function during multi-day races. METHODS: This prospective study recruited 10 Taiwanese runners who were scheduled to participate in the 7-day 2008 Athens Ultramarathon Festival Race, and three of them were chronic carriers of HBV. Blood samples were collected before, during, and 3 days after the race, including alkaline phosphatase (ALP), albumin (ALB), total protein (TP) levels, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (T-BIL) RESULTS: Ten Taiwanese runners (40% female; average age 52.3 +/- 7.9 years) who all planned to run in the race were recruited. Three runners were chronic carriers of HBV (HBV carrier), and all participants were anti-HCV antibody-negative and anti-hepatitis A virus (HAV) IgG-positive. There were no significant time-by-group effects on ALP, ALB, and TP levels, but the change over time effects were significant (p < 0.001, p = 0.001 and p = 0.010, respectively). ALT, AST, and T-BIL increased significantly to markedly higher levels in the HBV carrier group compared to the non-carrier group (group effect p = 0.009, p = 0.004, and p = 0.05, respectively), and the time-by-group interaction was also significant for these liver function markers (p < 0.001, p < 0.001, and p = 0.001, respectively). CONCLUSION: Compared to their counterparts, runners who are HBV carriers had significantly greater increases in levels of ALT, AST, and T-BIL during a 7-day ultramarathon, indicating that the liver function of carriers is more highly impacted in these races. PMID- 26809860 TI - Lead by example: should sport take a stand against brands of unhealthy consumption? PMID- 26809861 TI - The experience of potentially vulnerable people during cold weather: implications for policy and practice. AB - OBJECTIVES: To examine the experience of potentially vulnerable people during cold weather to inform interventions aimed at improving well-being. STUDY DESIGN: Qualitative study. METHODS: Telephone interviews with 35 individuals who could be considered to be potentially vulnerable during cold weather. Individuals were interviewed on two occasions during the winter of 2012-13, one or two days after a level 3 cold weather alert, as defined by the Cold Weather Plan for England, had been issued. RESULTS: Participants were largely unaware of the health risks associated with low temperatures, especially cardiovascular risk. There was a clear distinction between the thermal experience of people in social housing, which was newer, had efficient heating, was well insulated and well-maintained, and owner occupiers living in older, harder to heat homes. Most participants relied on public transport, and many faced arduous journeys to reach basic facilities. Vulnerability to cold was mediated to a significant extent by practical social support from family members. CONCLUSIONS: Resources should be targeted at people in hard to heat homes and those that are socially isolated. The repertoire of initiatives aimed at reducing cold-related mortality and morbidity could usefully be augmented by efforts to reduce social isolation and build community resilience. PMID- 26809862 TI - Individual and neighbourhood social capital and all-cause mortality in Brazilian adults: a prospective multilevel study. AB - OBJECTIVE: The relationship between social capital and mortality is not clear cut. There have been few longitudinal studies investigating this association so far. The objective was to assess the effect of different dimensions of social capital on mortality among adults of a Brazilian city. STUDY DESIGN: This is a prospective multilevel study. Baseline data were obtained from a population-based random sample of 846 adults (aged 18 years or more) residing in 38 neighbourhoods (census blocks). METHODS: Participants were interviewed in 2006-7 and their vital status investigated in 2013. Social capital was assessed by five scales (social cohesion, informal social control, neighbours' support, social action and political efficacy). The outcome was all-cause mortality. Data analysis used multilevel logistic regression models. RESULTS: At the individual level social cohesion was positively related to mortality in the unadjusted model but this association lost significance after adjustment for other variables in multivariable models. At the neighbourhood level, high mortality rates were associated with low social action independently of demographic, socio-economic, behavioural and health-related variables. CONCLUSION: We found more evidence for a contextual than individual level effect of social capital on mortality. PMID- 26809863 TI - Chronic kidney disease referral practices among non-nephrology specialists: A single-centre experience. AB - BACKGROUND: Early referral of CKD patients to nephrology teams (NT) is vital to identify patients most likely to progress, delay decline of excretory function, and provide planned RRT. Unfortunately, many are still being referred late. METHODS: We conducted a retrospective analysis to investigate referral rates, predictors of non-referral, and performed urine investigations in hospitalised CKD patients. RESULTS: Out of 388 patients studied, 5.6%, 11.4%, and 16.4% in CKD3A, 3B, and 4+5, respectively, were referred to an NT upon discharge (CKD3A vs. CKD4+5, p=0.016). For every additional year of age, the odds of being referred decreased by 5% (OR: 0.95, CI: 0.92-0.98, p=0.003). Patients were more likely to be referred to an NT if they were males (OR: 2.31, CI: 1.09-4.90, p=0.029) and having reached CKD 4+5 (OR: 3.99, CI: 1.58-10.10, p=0.003). Only 28.8%, 43.9%, and 50.7% of patients with CKD3A, 3B, and 4+5 were followed up with urine investigations after discharge (p=0.001). CKD stage 3B (OR: 3.54, CI: 1.23 10.19, p=0.019), CKD stage 4+5 (OR: 6.06, CI: 1.69-21.67, p=0.006), DM (OR: 6.28, CI: 2.38-16.58, p<0.0001), and having been referred to a NT (OR: 20.95, CI: 3.54 123.92, p=0.001) were independent predictors for having urine investigations. CONCLUSION: The highest rate of referral was achieved in males, younger age group, and those who have reached CKD stage 4+5. Urine tests remain largely underutilised and only a minority (16.4%) of patients with an eGFR <30mL/min/1.73m(2) were referred to a NT. PMID- 26809864 TI - Carbon monoxide poisoning and risk for ischemic stroke. PMID- 26809865 TI - Profile of serum biomarkers in eosinophilic disorders. PMID- 26809866 TI - Renal insufficiency and mortality in coronary artery disease with reduced ejection fraction. AB - BACKGROUND: Despite strong evidence linking decreased estimated glomerular filtration rate (eGFR) to worse cardiovascular outcome, the impact of eGFR on mortality in coronary artery disease (CAD) patients with different left ventricular ejection fraction (EF) is not well defined. METHODS: A retrospective cohort study. From Jul. 2008 to Jan. 2012, consecutive patients with CAD of West China Hospital were enrolled and were grouped into 3 eGFR categories: >=90, 60 90, and <60mL/min/1.73m(2). Patients with EF>=50% or <50% were defined as preserved EF or reduced EF, respectively. The endpoints were all-cause mortality and cardiac mortality. RESULTS: There are 2161 patients according to the inclusion criteria and follow-up requirement. The mean follow-up time was 30.97+/ 11.70months. Cumulative survival curves showed that in patients with reduced EF, renal insufficiency significantly increases all-cause mortality and cardiovascular mortality in a graded fashion (mortality rate, moderate or severe vs. normal: 29.3% vs. 5.4%, p<0.001; cardiac mortality rate, moderate or severe vs. normal: 18.2% vs. 4.5%, p=0.001, respectively). Cox regression analysis showed that in CAD patients with reduced EF, moderate to severe renal insufficiency increased all-cause mortality by 6.10-fold (HR 6.10, 95% CI 2.50 to 14.87) and cardiac mortality by 4.10-fold (HR 4.10, 95% CI 1.51 to 11.13). Use of beta-blockers, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), and statins was associated with decreased risk of mortality, but the use was lower in renal insufficiency patients, especially in combination of reduced EF. CONCLUSION: This study has found that the effect of renal function on prognosis in patients with CAD is closely related to cardiac function. In patients with reduced EF, renal insufficiency accompanies the higher risks of all-cause mortality and cardiovascular mortality. A higher number of treatments from beta-blocker, ACEIs or ARBs, and statin therapy were associated with decreased risk of mortality, even in the combination of renal insufficiency or declining cardiac function. PMID- 26809867 TI - Feasibility of Simple Traction Technique for Rectal Endoscopic Submucosal Dissection. AB - BACKGROUND AND AIMS: Rectal endoscopic submucosal dissection (ESD) is a highly effective procedure that achieves high en bloc resection regardless of lesion size or location. However, rectal ESD has a higher risk of intraoperative and postoperative bleeding and still difficult for beginners. Therefore, we designed a novel traction technique "traction-assisted rectal ESD using a clip-with-line (TAREC)," and investigated its feasibility. METHODS: Between December 2014 and July 2015, ten patients with rectal neoplasms (median size 36 mm; range 20-125 mm) were treated using the TAREC technique. RESULTS: In all lesions, good visibility of the submucosal layer was obtained, and the submucosal layer was dissected easily under direct visualization. All lesions were removed en bloc, and there were no procedure-related adverse events including postoperative bleeding. In particular, we experienced no intraoperative bleeding, which may be difficult to stop in some circumstances. CONCLUSIONS: The TAREC technique is a simple and generally applicable procedure. This technique is feasible for rectal ESD. PMID- 26809868 TI - Treatment of Crohn's Disease with an IgG4-Guided Exclusion Diet: A Randomized Controlled Trial. AB - BACKGROUND AND AIM: We previously reported an improvement in symptoms in Crohn's disease following an IgG4-guided exclusion diet in an open-label study. We aimed to evaluate, in a double-blinded randomized sham-controlled setting, the efficacy of IgG4-guided diet in improving quality of life in patients with Crohn's disease. METHODS: Consecutive patients with Crohn's disease and a Crohn's disease activity index (CDAI) of 80-400 attending tertiary and secondary care centers were screened. All patients had IgG4 titers tested against 16 common food types using ELISA. The true diet group excluded four food types with the highest antibody titers for 4 weeks, and the sham group excluded four foods with the lowest antibody titers. Quality of life was assessed using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) at beginning and end of the trial. Secondary outcome measures were CDAI, Harvey Bradshaw index, serum C-reactive protein, and fecal calprotectin. RESULTS: One hundred and forty-five subjects were screened and 96 subjects had initial food antibody testing performed with 76 patients completing the study. Milk, beef, pork and egg were the most commonly excluded food types in the true diet group. There was a 3.05 (0.01-6.11) p < 0.05 improvement in SIBDQ and 41 (10.4-71.5) in CDAI p = 0.009. CONCLUSION: IgG4 guided exclusion diet, as an adjunct, can improve quality of life and symptoms in patients with CD. PMID- 26809869 TI - The Diagnostic Yield of Repeated Endoscopic Evaluation in Patients with Gastrointestinal Bleeding and Left Ventricular Assist Devices. AB - INTRODUCTION: Left ventricular assist devices (LVADs) are increasingly common in patients with advanced heart failure. GI bleeding (GIB) occurs in 20-30 % of these patients and can arise anywhere in the GI tract. Given the high rates of GIB in this population, our aim was to determine the diagnostic yield of repeated endoscopic evaluation in these patients. METHODS: We performed a retrospective review of all 257 patients who had LVADs placed between 2008 and 2013 at Duke University Hospital and identified all patients who underwent any endoscopic evaluation for GIB. RESULTS: Of the 257 patients with LVADs placed, 78 (30 %) underwent at least one endoscopy for GIB. A source was identified in 36 % of cases, most commonly angioectasias (53.6 %). Treatment was performed in 67.9 % of patients and hemostasis was achieved in all. 64.1 % of the cohort underwent a second endoscopy for GIB. 42.9 % of these exams revealed a bleeding source. Endoscopic treatment was employed in 76.2 %. 38.5 % of the cohort underwent a third endoscopic exam for bleeding and a source was identified in 53.3 % with angioectasias remaining most common (56.3 %). By Fisher's exact and Chi-square testing, only the presence of a bleeding source (p = 0.0034) and use of hemostatic therapy (p = 0.0127) on the index examination were significantly associated with re-bleeding. CONCLUSIONS: GIB is common in patients with LVADs. The diagnostic and therapeutic yield of endoscopy is remains high with repeated interventions. Despite these high yields, a large portion of the cohort requires repeated interventions for recurrent bleeding. PMID- 26809870 TI - Prevention of Esophageal Strictures After Endoscopic Submucosal Dissection: A Promising Therapy Using Carboxymethyl Cellulose Sheets. AB - BACKGROUND: Esophageal stricture is one of the serious adverse events following endoscopic submucosal dissection (ESD). However, optimum preventive techniques are still lacking. AIMS: Our primary objective was to evaluate the incidence of post-ESD esophageal stricture with the application of carboxymethyl cellulose (CMC) sheets. Secondary objectives were to determine the number of sessions of endoscopic balloon dilatation (EBD) required to resolve post-ESD strictures and the incidence rate of peri-operative adverse events. METHODS: This was a pilot, single-center, prospective study. Seven patients who had high risks of developing post-ESD esophageal stricture were enrolled into our study. CMC sheets were applied to the mucosal defects immediately after the completion of ESD. Patients were monitored and reviewed after ESD to detect any adverse events. RESULTS: The incidence rate of post-operative stricture was 57 % (4/7 patients). Among patients who required EBD, the number of sessions performed was 2.8 +/- 2.2. No serious post-operative adverse events were reported. CONCLUSION: The use of CMC sheets appears to be a safe and effective prophylactic treatment for esophageal stricture following extensive ESD. PMID- 26809871 TI - Risk of Advanced Colorectal Neoplasia According to the Number of High-Risk Findings at Index Colonoscopy: A Korean Association for the Study of Intestinal Disease (KASID) Study. AB - BACKGROUND: Data regarding outcomes for patients with multiple findings for high risk adenomas are scarce. AIM: To compare the risk for colorectal neoplasm (CRN) recurrence according to the number of high-risk findings. METHODS: This was a retrospective and multicenter study. Patients who had one or more high-risk adenomas at the index colonoscopy and underwent follow-up colonoscopy 2.5 or more years after the index colonoscopy were included. The number of high-risk findings was defined as follows: number of adenomas larger than 1 cm + number of adenomas with HGD + number of adenomas with a villous component + existence (counted as 1) or nonexistence (counted as 0) of three or more adenomas. RESULTS: A total of 1646 patients were included, and the mean duration between index and follow-up colonoscopy was approximately 4 years. The cumulative incidence rate of recurrent advanced CRN in patients with three or more high-risk findings was higher than that in patients with one or two high-risk findings (p < 0.001). However, the difference in 3-year cumulative incidence rates of recurrent advanced CRN between the two groups was not great, although it was statistically significant (4.8 vs. 2.3 %, p = 0.039). CONCLUSIONS: A 3-year surveillance interval for patients with multiple high-risk findings, regardless of the number of high-risk findings, appears reasonable. PMID- 26809872 TI - Radiographic and Histologic Findings of a Rare Liver Tumor-Hepatic Epithelioid Hemangioendothelioma. PMID- 26809875 TI - Editorial. PMID- 26809874 TI - Defining the optimal cut-off values for liver enzymes in diagnosing blunt liver injury. AB - BACKGROUND: Patients with blunt trauma to the liver have elevated levels of liver enzymes within a short time post injury, potentially useful in screening patients for computed tomography (CT). This study was performed to define the optimal cut off values for serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in patients with blunt liver injury diagnosed with contrast enhanced multi detector-row CT (CE-MDCT). METHODS: All patients admitted from May 2006 to July 2013 to Teikyo University Hospital Trauma and Critical Care Center, and who underwent abdominal CE-MDCT within 3 h after blunt trauma, were retrospectively enrolled. Using receiver operating characteristic (ROC) curve analysis, the optimal cut-off values for AST and ALT were defined, and sensitivity and specificity were calculated. RESULTS: Of a total of 676 blunt trauma patients 64 patients were diagnosed with liver injury (Group LI+) and 612 patients without liver injury (Group LI-). Group LI+ and LI- were comparable for age, Revised Trauma Score, and Probability of survival. The groups differed in Injury Severity Score [median 21 (interquartile range 9-33) vs. 17 (9-26) (p < 0.01)]. Group LI+ had higher AST than LI- [276 (48-503) vs. 44 (16-73); p < 0.001] and higher ALT [240 (92-388) vs. 32 (16-49); p < 0.001]. Using ROC curve analysis, the optimal cut-off values for AST and ALT were set at 109 U/l and 97 U/l, respectively. Based on these values, AST >= 109 U/l had a sensitivity of 81%, a specificity of 82%, a positive predictive value of 32%, and a negative predictive value of 98%. The corresponding values for ALT >= 97 U/l were 78, 88, 41 and 98%, respectively, and for the combination of AST >= 109 U/l and/or ALT >= 97 U/l were 84, 81, 32, 98%, respectively. CONCLUSIONS: We have identified AST >= 109 U/l and ALT >= 97 U/l as optimal cut-off values in predicting the presence of liver injury, potentially useful as a screening tool for CT scan in patients otherwise eligible for observation only or as a transfer criterion to a facility with CT scan capability. PMID- 26809873 TI - Cardiovascular Disease and Myocardial Abnormalities in Nonalcoholic Fatty Liver Disease. AB - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in many developed countries, affecting an estimated 30 % of the adult population. In this updated clinical review, we summarize the current knowledge regarding the strong association between NAFLD and the risk of coronary heart disease (CHD) and other functional, structural, and arrhythmic cardiac complications (e.g., left ventricular dysfunction, heart valve diseases and atrial fibrillation). We also briefly discuss the putative biological mechanisms linking NAFLD with these important extra-hepatic complications. To date, a large body of evidence has suggested that NAFLD is not simply a marker of CHD and other functional, structural, and arrhythmic cardiac complications, but also may play a part in the development and progression of these cardiac complications. The clinical implication of these findings is that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions aimed at decreasing the risk of CHD and other cardiac and arrhythmic complications. PMID- 26809876 TI - Preface. PMID- 26809878 TI - Anatomical distribution and gross pathology of wounds in necropsied farmed mink (Neovison vison) from June and October. AB - BACKGROUND: Wounds are regarded as an indicator of reduced welfare in mink production; however, information on the occurrence and significance of wounds is sparse. To provide a basis for assessment and classification of wounds in farmed mink, the distribution pattern and characteristics of wounds in farmed mink in June and October, respectively, is described. A total of 791 and 660 mink from 6 to 12 Danish mink farms, respectively, were examined. The mink were either found dead or were euthanized due to injury or other disease. Mink included from June were kits in the pre-weaning and weaning period (1-2 months old). Mink included from October were juveniles in the late growth period (approximately 5-6 months old) or older. Macroscopic pathology and wound location was systematically recorded. RESULTS: There was considerable variation in morphology as well as location of wounds between June and October. Wounds were primarily located on the front parts of the body and in the head in June (1-2 month old kits) and mainly on the rear parts of the body and on the tail in October (5-6 month old kits and older). Moreover, there were significantly more females than males with wounds for most wound types, and significant differences in occurrence of ear and tail base wounds between certain colour types. CONCLUSIONS: Wounds varied significantly from June to October with respect to morphology and anatomical location. Wounds in June were primarily located on the front parts of the body and in the head, while wounds in October were mainly present on the hind parts of the body and on the tail. The majority of the wounds were found in specific well defined skin areas and could therefore be grouped into categories according to anatomical location. PMID- 26809881 TI - 'Tweaking' the model for understanding and preventing maternal and neonatal morbidity and mortality in Low Income Countries: "inserting new ideas into a timeless wine skin". AB - BACKGROUND: Maternal and neonatal morbidity and mortality in Low Income Countries, especially in sub-Saharan Africa involves numerous interrelated causes. The three-delay model/framework was advanced to better understand the causes and associated Contextual factors. It continues to inform many aspects of programming and research on combating maternal and child morbidity and mortality in the said countries. Although this model addresses some of the core areas that can be targeted to drastically reduce maternal and neonatal morbidity and mortality, it potentially omits other critical facets especially around primary prevention, and pre- and post-hospitalization continuum of care. DISCUSSION: The final causes of Maternal and Neonatal mortality and morbidity maybe limited to a few themes largely centering on infections, preterm births, and pregnancy and childbirth related complications. However, to effectively tackle these causes of morbidity and mortality, a broad based approach is required. Some of the core issues that need to be addressed include:-i) prevention of vertically transmitted infections, intra-partum related adverse events and broad primary prevention strategies, ii) overall health care seeking behavior and delays therein, iii) quality of care at point of service delivery, and iv) post-insult treatment follow up and rehabilitation. In this article we propose a five-pronged framework that takes all the above into consideration. This frameworks further builds on the three-delay model and offers a more comprehensive approach to understanding and preventing maternal and neonatal morbidity and mortality in Low Income Countries CONCLUSION: In shaping the post 2015 agenda, the scope of engagement in maternal and newborn health need to be widened if further gains are to be realized and sustained. Our proposed five pronged approach incorporates the need for continued investment in tackling the recognized three delays, but broadens this to also address earlier aspects of primary prevention, and the need for tertiary prevention through ongoing follow up and rehabilitation. It takes into perspective the spectrum of new evidence and how it can be used to deepen overall understanding of prevention strategies for maternal and neonatal morbidity and mortality in LICS. PMID- 26809882 TI - In vitro efficacy of shampoos containing miconazole, ketoconazole, climbazole or accelerated hydrogen peroxide against Microsporum canis and Trichophyton species. AB - Objectives The objective was to evaluate the antifungal efficacy of shampoo formulations of ketoconazole, miconazole or climbazole and accelerated hydrogen peroxide wash/rinse against Microsporum canis and Trichophyton species spores. Methods Lime sulfur (1:16)-treated control, enilconazole (1:100)-treated control, accelerated hydrogen peroxide (AHP 7%) 1:20 and a 1:10 dilution of shampoo formulations of miconazole 2%, miconazole 2%/chlorhexidine gluconate 2-2.3%, ketoconazole 1%/chlorhexidine 2%, climbazole 0.5%/chlorhexidine 3% and sterile water-untreated control were tested in three experiments. In the first, a suspension of infective spores and hair/scale fragments was incubated with a 1:10, 1:5 and 1:1 dilution of spores to test solutions for 10 mins. In the second, toothbrushes containing infected cat hair in the bristles were soaked and agitated in test solutions for 10 mins, rinsed, dried and then fungal cultured (n = 12*). In the third, a 3 min contact time combined with an AHP rinse was tested (n = 10*). Good efficacy was defined as no growth. Results Water controls grew >300 colony-forming units/plate and all toothbrushes were culture-positive prior to testing. For the suspension tests, all test products showed good efficacy. Miconazole 2%, ketoconazole 1% and AHP showed good efficacy after a 10 min contact time. Good efficacy was achieved with a shorter contact time (3 mins) only if combined with an AHP rinse. Conclusions and relevance Lime sulfur and enilconazole continued to show good efficacy. In countries or situations where these products cannot be used, shampoos containing ketoconazole, miconazole or climbazole are alternative haircoat disinfectants, with a 10 min contact time or 3 mins if combined with an AHP rinse. PMID- 26809883 TI - Graphene homojunction: closed-edge bilayer graphene by pseudospin interaction. AB - Depending on the sublattices they are propagated in, low-energy electrons or holes are labeled with pseudospin. By engineering pseudospin interactions, we propose that two critical features of a junction, i.e., band gap opening and spatial charge separation, can be realized in graphene layers with proper stacking. We also demonstrate theoretically that such a graphene diode may play a role in future pseudospin electronics such as for harvesting solar energy. PMID- 26809884 TI - Smoking Cessation Intervention Preferences Among Urban African Americans: A Mixed Methods Approach. AB - African Americans suffer disproportionately from smoking-related morbidity and mortality and make more quit attempts but report less success in quitting. Smokers tend to identify more strongly with African American culture. Qualitative interviews were conducted to elicit perceptions toward smoking and intervention content. Seventy-one African American smokers recruited from community locations participated. The majority stated they would not use any cessation aids if trying to quit smoking, despite the availability of free nicotine replacement. Acculturative stress scores were significantly higher in younger participants and those with higher income. Higher African American acculturation did not predict smoking cessation intervention preference. Family and social relationships were cited as both reasons for wanting to quit and reasons for continuing to smoke. Based on these findings, interventions for urban African Americans should address household members continuing to smoke, social/family connections, stress management, and cultural identification in urban areas. PMID- 26809885 TI - Malaria community health workers in Myanmar: a cost analysis. AB - BACKGROUND: Myanmar has the highest malaria incidence and attributed mortality in South East Asia with limited healthcare infrastructure to manage this burden. Establishing malaria Community Health Worker (CHW) programmes is one possible strategy to improve access to malaria diagnosis and treatment, particularly in remote areas. Despite considerable donor support for implementing CHW programmes in Myanmar, the cost implications are not well understood. METHODS: An ingredients based micro-costing approach was used to develop a model of the annual implementation cost of malaria CHWs in Myanmar. A cost model was constructed based on activity centres comprising of training, patient malaria services, monitoring and supervision, programme management, overheads and incentives. The model takes a provider perspective. Financial data on CHWs programmes were obtained from the 2013 financial reports of the Three Millennium Development Goal fund implementing partners that have been working on malaria control and elimination in Myanmar. Sensitivity and scenario analyses were undertaken to outline parameter uncertainty and explore changes to programme cost for key assumptions. RESULTS: The range of total annual costs for the support of one CHW was US$ 966-2486. The largest driver of CHW cost was monitoring and supervision (31-60% of annual CHW cost). Other important determinants of cost included programme management (15-28% of annual CHW cost) and patient services (6 12% of annual CHW cost). Within patient services, malaria rapid diagnostic tests are the major contributor to cost (64% of patient service costs). CONCLUSION: The annual cost of a malaria CHW in Myanmar varies considerably depending on the context and the design of the programme, in particular remoteness and the approach to monitoring and evaluation. The estimates provide information to policy makers and CHW programme planners in Myanmar as well as supporting economic evaluations of their cost-effectiveness. PMID- 26809888 TI - Synthesis and Pharmacological Evaluation of Novel Adenine-Hydrogen Sulfide Slow Release Hybrids Designed as Multitarget Cardioprotective Agents. AB - This work deals with the design, synthesis, and evaluation of the cardioprotective properties of a number of novel hybrid compounds combining the adenine nucleus with a suitable H2S slow-releasing moiety, coupled via a stable ether bond. The H2S release rate of the hybrids and their ability to increase cGMP were estimated in vitro. The most promising derivatives 4 and 11, both containing 4-hydroxythiobenzamide moiety as H2S donor, were selected for further in vivo evaluation. Their ability to release H2S in vivo was recorded using a new fully validated UPLC-DAD method. Both compounds reduced significantly the infarct size when administered at the end of sustained ischemia. Mechanistic studies showed that they conferred enhanced cardioprotection compared to adenine or 4 hydroxythiobenzamide. They activate the PKG/PLN pathway in the ischemic myocardium, suggesting that the combination of both pharmacophores results in synergistic cardioprotective activity through the combination of both molecular pathways that trigger cardioprotection. PMID- 26809889 TI - How many pictures are demanded for screening gastroscopy? PMID- 26809891 TI - India has world's highest number of stillbirths. PMID- 26809892 TI - Graphene Oxide Catalyzed C-H Bond Activation: The Importance of Oxygen Functional Groups for Biaryl Construction. AB - A heterogeneous, inexpensive, and environmentally friendly graphene oxide catalytic system for the C-H bond arylation of benzene enables the formation of biaryl compounds in the presence of aryl iodides. The oxygen functional groups in these graphene oxide sheets and the addition of KOtBu are essential for the observed catalytic activity. Reactions with various model compounds and DFT calculations confirmed that these negatively charged oxygen atoms promote the overall transformation by stabilizing and activating K(+) ions, which in turns facilitates the activation of the C-I bond. However, the graphene pi system also greatly facilitates the overall reaction as the aromatic coupling partners are easily adsorbed. PMID- 26809899 TI - Tolerance of a high-protein baked-egg product in egg-allergic children. AB - BACKGROUND: Egg allergy is one of the most common immunoglobulin E (IgE)-mediated food allergies. Extensively heating egg has been found to decrease its allergenicity and 64% to 84% of children allergic to egg have been found to tolerate baked-egg products. Because there is no reliable method for predicting baked-egg tolerance, oral food challenges remain the gold standard. Prior studies have reported on baked-egg challenges using up to 2.2 g of egg white (EW) protein. OBJECTIVE: To establish whether children with egg allergy would pass a baked-egg challenge to a larger amount of egg protein and the potential criteria for predicting the likelihood of baked-egg tolerance. METHODS: A chart review was conducted of all patients 6 months to 18 years of age with egg allergy who underwent oral baked-egg challenges at Children's Medical Center Dallas over a 2 year period. Challenges were conducted in the clinic with a 3.8-g baked-egg product. RESULTS: Fifty-nine of 94 patients (63%) tolerated the 3.8-g baked-egg product. The presence of asthma (P < .01), EW skin prick test (SPT; P < .01) reactive wheal, and EW-specific IgE level (P = .02) correlated with baked-egg reactivity, whereas ovomucoid-specific IgE level did not. The positive predictive value approached 66% at an EW SPT reactive wheal of 10 mm and 60% for an EW specific IgE level of 8 kUA/L. CONCLUSION: Most subjects with egg allergy tolerated baked egg. This study is the first to use 3.8 g of EW protein for the challenges. The EW SPT wheal diameter and EW-specific IgE levels were the best predictors of baked-egg tolerance. PMID- 26809901 TI - A cross-cultural study on perceived health-related quality of life in children and adolescents with type 1 diabetes mellitus. AB - OBJECTIVE: This study investigated whether culture can affect self- and proxy reports of perceived diabetes-specific health-related quality of life of children and adolescents with type 1 diabetes when taking into account glycemic control, gender and age. METHODS: A total of 416 patients aged between 8 and 18 years--84 (Greece), 135 (Hungary) and 197 (Kuwait)--and their parents completed the Pediatric Quality of Life Inventory 3.0. Diabetes Module. RESULTS: Gender and age did not have any effect on perceived diabetes-specific health-related quality of life. Significant differences were detected among countries in self- and proxy reports of diabetes-specific health-related quality of life when controlling for glycemic control. More specifically, Greek patients with type 1 diabetes and their parents reported significantly worse disease-specific health-related quality of life than their peers from Kuwait and Hungary. Moreover, culture affected the level of agreement between self- and proxy-reports with parents from Kuwait underestimating their children's diabetes-specific health-related quality of life. CONCLUSION: The impact of culture on self- and proxy-reports of diabetes specific health-related quality of life warrants further investigation, since it might suggest the need for differential psychosocial treatment. PMID- 26809902 TI - Abnormalities of retinal ganglion cell complex at optical coherence tomography in patients with type 2 diabetes: a sign of diabetic polyneuropathy, not retinopathy. AB - AIMS: To compare optical coherence tomography (OCT)-derived neuro-retinal parameters in patients with type 2 diabetes and non-diabetic controls and to evaluate their correlation with diabetic retinopathy (DR) and polyneuropathy (DPN). METHODS: One-hundred consecutive patients with type 2 diabetes were examined by spectral-domain (SD) OCT for evaluating ganglion cell complex (GCC) and retinal nerve fibre layer (RNFL) thickness and two new pattern-based quantitative measures of GCC damage, global and focal loss volume (GLV and FLV). Fifty sex- and age-matched non-diabetic subjects served as control. RESULTS: RNFL thickness (101.0+/-10.6 vs. 106.4+/-10.3 MUm, P=0.003) was significantly lower and GLV (6.58+/-4.98 vs. 4.52+/-3.10 %, P=0.008) and FLV (1.90+/-1.97 vs. 0.89+/ 0.84 %, P<0.0001) were significantly higher in diabetic versus control subjects. The OCT parameters did not differ significantly according to DR grade. Conversely, RNFL thickness was lower and GLV and FLV were higher in patients with versus those without DPN, and the extent of changes increased significantly with quartiles of DPN score. At both bivariate and multivariate analysis, OCT parameters, especially FLV, correlated significantly with DPN measures. CONCLUSIONS: The GCC is significantly affected in patients with type 2 diabetes and SD-OCT might represent a useful tool to detect DPN, but not DR in these individuals. PMID- 26809903 TI - Changes in glucose-elicited blood metabolite responses following weight loss and long term weight maintenance in obese individuals with impaired glucose tolerance. AB - AIMS: Weight loss improves insulin sensitivity and glucose tolerance in obese subjects with impaired glucose tolerance (IGT), but the long term dynamic effects on blood metabolites other than glucose during an oral glucose tolerance test (OGTT), are largely unknown. Here, we studied changes in OGTT-elicited metabolite patterns in obese subjects during a diet-induced weight loss study. METHODS: Blood samples from 14 obese individuals with IGT were collected at 0, 30 and 120 min during a standard 75 g OGTT at baseline (BMI 44 +/- 2 kg/m(2)), after weight loss (BMI 36 +/- 2 kg/m(2)) and after weight maintenance (BMI 35 +/- 2 kg/m(2)). Serum metabolite levels were analyzed by gas chromatography/mass spectrometry and compared to a lean glucose tolerant group. RESULTS: Changes in the OGTT-elicited metabolite patterns occurred differentially during weight loss and weight maintenance. Enhanced suppression of aromatic amino acids were associated with decreased insulinogenic index observed after weight loss (tyrosine: r=0.72, p=0.013; phenylalanine: r=0.63, p=0.039). The OGTT-elicited suppression and/or lack of increase in levels of glutamate, glutamine, isoleucine, leucine, and the fatty acids laurate, oleate and palmitate, improved towards the lean profile after weight maintenance, paralleling an improvement in glucose tolerance. The greater heterogeneity in the response before and after weight loss in the obese, compared to lean subjects, was markedly reduced after weight maintenance. CONCLUSIONS: Diet-induced weight loss followed by weight maintenance results in changes in metabolite profiles associated with either hepatic insulin sensitivity or peripheral glucose tolerance. Our results highlight the importance of evaluating the effects of weight loss and weight maintenance separately. PMID- 26809904 TI - Systolic blood pressure variability and lower extremity amputation in a non elderly population with diabetes. AB - OBJECTIVE: Systolic blood pressure (SBP) variability is emerging as a new risk factor for cardiovascular diseases, diabetic nephropathy, and other atherosclerotic conditions. Our objective is to examine whether it has any prognostic value for lower-extremity amputations. RESEARCH DESIGN AND METHODS: This is a nested case-control study of a cohort of patients with diabetes aged<60 years and treated in the US Department of Veterans Healthcare system in 2003. They were followed over five years for any above-ankle (major) amputations. For each case with a major amputation (event), we randomly selected up to five matched controls based on age, sex, race/ethnicity, and calendar time. SBP variability was computed using three or more blood pressure measures taken during the one-year period before the event. Patients were classified into quartiles according to their SBP variability. RESULTS: The study sample included 1038 cases and 2932 controls. Compared to Quartile 1 (lowest variability), Quartile 2 had 1.4 times (OR=1.44, 95% CI=1.00-2.07) and Quartiles 3 and 4 (highest) had 2.5 times (OR for Quartile 3=2.62, 95% CI=1.85-3.72; OR for Quartile 4=2.50, 95% CI=1.74-3.59) higher risk of major amputation (P for trend<0.001). This gradient relationship held in both normotensive and hypertensive groups as well as for individuals without prior peripheral vascular disease. CONCLUSIONS: This is the first study to show a significant graded relationship between SBP variability and risk of major amputation among non-elderly persons with diabetes. PMID- 26809905 TI - Type 2 diabetic patient with a foot ulcer as initial manifestation of diffuse large B-cell lymphoma: A case report. AB - Diabetic foot ulcerations (DFU) represent a major cause of hospitalization and amputation. In people with diabetes it's not uncommon to find chronic wounds due to pathogenic mechanisms different from diabetes. Here we report the case of a foot lesion misdiagnosed as DFU but actually caused by diffuse large B-cell lymphoma. PMID- 26809907 TI - Ecomorphological convergence in planktivorous surgeonfishes. AB - Morphological convergence plays a central role in the study of evolution. Often induced by shared ecological specialization, homoplasy hints at underlying selective pressures and adaptive constraints that deterministically shape the diversification of life. Although midwater zooplanktivory has arisen in adult surgeonfishes (family Acanthuridae) at least four independent times, it represents a clearly specialized state, requiring the capacity to swiftly swim in midwater locating and sucking small prey items. Whereas this diet has commonly been associated with specific functional adaptations in fishes, acanthurids present an interesting case study as all nonplanktivorous species feed by grazing on benthic algae and detritus, requiring a vastly different functional morphology that emphasizes biting behaviours. We examined the feeding morphology in 30 acanthurid species and, combined with a pre-existing phylogenetic tree, compared the fit of evolutionary models across two diet regimes: zooplanktivores and nonzooplanktivorous grazers. Accounting for phylogenetic relationships, the best fitting model indicates that zooplanktivorous species are converging on a separate adaptive peak from their grazing relatives. Driving this bimodal landscape, zooplanktivorous acanthurids tend to develop a slender body, reduced facial features, smaller teeth and weakened jaw adductor muscles. However, despite these phenotypic changes, model fitting suggests that lineages have not yet reached the adaptive peak associated with plankton feeding even though some transitions appear to be over 10 million years old. These findings demonstrate that the selective demands of pelagic feeding promote repeated - albeit very gradual - ecomorphological convergence within surgeonfishes, while allowing local divergences between closely related species, contributing to the overall diversity of the clade. PMID- 26809908 TI - The impact of breastfeeding peer support for mothers aged under 25: a time series analysis. AB - Breastfeeding has known positive health benefits for babies and mothers, yet the UK has one of the lowest breastfeeding initiation rates in Europe. Despite national guidance that recommends provision of breastfeeding peer support, there is conflicting evidence regarding its effectiveness, especially in high-income countries, and a lack of evidence among young mothers. This study evaluates the effectiveness of a breastfeeding peer support service (BPSS) in one UK city in increasing breastfeeding initiation and duration in young mothers. Routinely collected data were obtained on feeding method at birth, 2 and 6 weeks for all 5790 women aged <25 registered with a local general practitioner and who gave birth from April 2009 to September 2013. Segmented regression was used to quantify the impact of the introduction of the BPSS in September 2012 on the prevalence of breastfeeding at birth, 2 and 6 weeks, accounting for underlying trends. Results showed that breastfeeding prevalence at birth and 2 weeks began to increase month-on-month after the introduction of the BPSS, where previous figures had been static; prevalence at birth increased by 0.55 percentage points per month (95% CI 0.10-1.00, P = 0.018) and at 2 weeks by 0.50 percentage points (95% CI 0.15-0.86, P = 0.007). There was no change from an underlying marginally increasing trend in prevalence at 6 weeks. In conclusion, our findings suggest that a one-to-one BPSS provided by paid peer supporters and targeted at young mothers in the antenatal and post-natal periods may be beneficial in increasing breastfeeding initiation and prevalence at 2 weeks. PMID- 26809910 TI - [Cloning DNA Vaccine Candidate SAG1 Gene of Toxoplasma gondii]. AB - OBJECTIVE: Toxoplasma gondii, which is observed in our country and worldwide, can cause mortality and is an important public health problem because of engaging babies from pregnant women. An effective vaccine against toxoplasmosis has not yet been developed. SAG1 protein is released from the bradyzoites and tachyzoites stages of T. gondii and is important at the pathogenesis of the disease. This study aimed to clone a promising DNA vaccine candidate, SAG1 gene, of T. gondii. METHODS: T. gondii genomic DNA was isolated from tachyzoites of T. gondii. SAG1 gene was amplified with specific primers and then cloned into the pJET1.2 vector. Recombinant plasmids were transformed into Escherichia coli cells. The presence of recombinant plasmids was determined by polymerase chain reaction (PCR) screening. Following the purification of the recombinant plasmid from positive colonies, cloning was confirmed by PCR, restriction enzyme assays, and DNA sequence analysis. RESULTS: After PCR with SAG1 gene-specific primers, 1010-bp PCR products were obtained. Recombinant plasmid, which was transformed into competent E. coli cells, was verified by PCR screening. Moreover, PCR verified that the recombinant plasmids contained the SAG1 gene. The DNA sequence was analyzed, and the DNA sequence was obtained. CONCLUSION: One of the promising DNA vaccine candidates against toxoplasmosis, SAG1 gene, has been cloned. PMID- 26809911 TI - In vitro and in vivo Nematocidal Activity of Allium sativum and Tagetes erecta Extracts Against Haemonchus contortus. AB - OBJECTIVE: In the Mexican ethno-medicine, a number of plants have shown a successful anthelmintic activity. This fact could be crucial to identify possible green anti-parasitic strategies against nematodes affecting animal production. This research evaluated the in vitro and in vivo nematocidal effects of two single and combined plant extracts: bulbs of Allium sativum (n-hexane) and flowers of Tagetes erecta (acetone). The in vivo assay evaluated the administration of extracts either individually or combined against Haemonchus contortus in experimentally infected gerbils. METHODS: The in vitro larvicidal activity percentage (LAP) of A. sativum and T. erecta extracts against H. contortus (L3) was determined by means of individual and combined usage of the extracts. Similarly, the extracts were evaluated in terms of reduction in the parasitic population in gerbils infected with H. contortus by individual and combined usage. RESULTS: The LAP at 40 mg/mL was 68% with A. sativum and 36.6% with T. erecta. The combination caused 83.3% mortality of parasites. The oral administration of A. sativum and T. erecta extracts at 40 mg/mL, caused 68.7% and 53.9% reduction of the parasitic burden, respectively. Meanwhile, the combined effect of both extracts shown 87.5% reduction. CONCLUSION: This study showed evidence about the effect of A. sativum and T. erecta plant extracts by means of individual and combined usage against H. contortus in in vitro and in vivo bioassays in artificially H. contortus-infected gerbils as a model. PMID- 26809912 TI - New species of Genus Diplotriaena Railliet and Henry, 1909 (Filariidae: Nematoda) from Passer domesticus Linnaeus and P. pyrhonotus Blyth (Passeridae: Passeriformes) in Jamshoro, Sindh, Pakistan. AB - OBJECTIVE: The present study was conducted to examine the filarial nematodes of house sparrow [Passer domesticus (Linnaeus, 1758)] and Sindh sparrow (P. pyrrhonotus Blyth, 1844) from Jamshoro, Sindh, Pakistan. METHODS: Twenty-three house sparrows and 12 Sindh sparrows were examined for nematode parasites. A total of seven birds were found infected by 16 filarial worms belonging to the genus Diplotriaena Railliet and Henry, 1909. Birds were dissected and parasites were processed through the standard method of temporary slide mounting. Live worms were found embedded in the lungs of the host. RESULT: The present specimens were known to be new to science. It is the first record of species of both domestic and Sindh sparrows in Pakistan. The prevalence and male-female ratio of the present species were conducted. CONCLUSION: The present species was named as Diplotriaena passeri. This name is given to new nematode species on the name of its type host. It was compared with previously known species of the genus Diplotriaena on the basis of their diagnostic characteristics. PMID- 26809913 TI - Risk Factors and Relationship Between Intestinal Parasites and the Growth Retardation and Psychomotor Development Delays of Children in Sanliurfa, Turkey. AB - OBJECTIVE: The objective of this study was to determine the risk factors for and relationship among parasitic infections, growth retardation, and psychomotor developmental delays in children aged 6 years and below. METHODS: This case control study was performed in Sanliurfa in southeastern Turkey between October and December 2007. Data were collected using a structured questionnaire, anthropometry, Ankara Development Screening Inventory, and laboratory analysis of stool specimens. RESULTS: The most common parasite was Giardia intestinalis (42.53%) followed by Enterobius vermicularis (27.58%), Ascaris lumbricoides (18.39%), Hymenolepis nana (5.75%), Trichuris trichiura (3.45%), Escherichia coli (1.15%), and Blastocystis spp. (1.15%). Fifty-eight percent of all children were infected with intestinal parasites; 55.2% had only one parasite, whereas 44.8% had multiple parasites. The children infected with G. intestinalis and other intestinal parasites had significantly higher levels of growth retardation and psychomotor development delay than non-infected children. Children with parasitic infections had growth delay up to 2.9 times, general development delay up to 1.9 times, language-cognitive development delay up to 2.2 times, and fine motor development delay up to 2.9 times higher than children without any parasitic infections. However, no significant relationship among intestinal parasites, gross motor development, social-self skills, and development delay was identified. The education level of parents, poor economic situation, number of households, not washing hands, playing with soil, family history of parasitic infection were the significant risk factors for intestinal parasites. CONCLUSION: Our study indicates that the presence of either malnutrition or intestinal parasites may put a child in a high-risk group for developmental delays and growth retardation. Therefore, public health interventions can embrace nationwide deworming in children. PMID- 26809914 TI - [Investigation of Intestinal Parasites and Level of Hygiene Knowledge of School Students]. AB - OBJECTIVE: In this study, the prevalence of intestinal parasites and its relationship with some hygiene habits and socio-demographic characteristics of students in Yigilca were investigated. METHODS: This study was conducted in three parts. Firstly, the prevalence of parasitic diseases was measured, and questionnaires about the level of knowledge of hygiene were administered. Secondly, control and intervention groups were determined. Lastly, some education and training courses were organized and provided to the intervention group, including parents and children, about the prevention of parasitic diseases and habits of cleaning. RESULTS: In this study, 540 cellophane tapes and 523 stool samples were studied. Among the samples analyzed, 87 (16.1%) with Enterobius vermicularis, 79 (15.1%) with Giardia intestinalis, 73 (13.9%) with various non pathogenic parasites, 1 (0.19%) with Ascaris lumbricoides, and 1 (0.19%) with Hymenolepis nana were found. G. intestinalis was highly positive among the children who do not wash their hands after defecation. Also, some intestinal parasites were found to be related to the socio-demographic characteristics of families; parental education, family income, and father's profession were found to be associated with the presence of intestinal parasites. After training, the intervention group showed a significant decrease in the number of giardiasis and enterobiasis cases. CONCLUSION: Education on hygiene will prevent parasitic diseases from an early age. PMID- 26809915 TI - Molecular Study of the G1 Haplotypes of Echinococcus granulosus from Iran Based on Cytochrome C Oxidase (Subunit 1) Sequence. AB - OBJECTIVE: In this study, we attempted to identify new Echinococcus granulosus isolates in the North West provinces of Iran based on the mitochondrial cytochrome c oxidase subunit 1 (CO1) sequence. METHODS: Twenty-nine hydatid cysts from sheep and goats were collected. Genomic DNAs were extracted, and a partial sequence of the CO1 gene was amplified. Polymerase chain reaction products were cloned and sequenced with M13 primers in both directions. RESULTS: All Iranian isolates were located in G1 and G3 genotypes. For the first time, a new G1 haplotype in two Iranian isolates were identified. CONCLUSION: It seems that this new haplotype was transmitted from Jordan to Iran or vice versa. PMID- 26809916 TI - [Detection of Anaplasma / Ehrlichia Species of Cattle and Ticks in Aydin Region]. AB - OBJECTIVE: The aim of this study is to detect the Anaplasma/Ehrlichia species of cattle and ticks and to provide knowledge on the prevalence of these species during sampling periods. METHODS: A total of 679 blood and 186 tick samples were collected from the Osmanbuku, Akcaova, Dalama, and Soke districts of Aydin. The samples were screened with genus polymerase chain reaction (PCR) for Anaplasma/Ehrlichia spp., species-specific polymerase chain reaction for Anaplasma marginale and A. centrale, and nested PCR for A. bovis and A. phagocytophilum. RESULTS: A. centrale was detected in Soke during September and in Dalama and Akcaova during March, June, September, and December. A. marginale was detected in Osmanbuku during June; in Soke during March and December; in Akcaova during June, September, and March; and in Dalama during the entire sampling period. A. phagocytophilum was detected in all regions during the entire sampling period. None of the samples were positive for A. bovis. Mixed infections were detected in 50 blood samples. A. marginale and A. phagocytophilum were detected in the tick samples. CONCLUSION: In this study, A. phagocytophilum was abundantly detected compared with A. marginale and A. centrale. A. phagocytophilum and A. centrale were extensively found in Akcaova and A. marginale was mostly seen in Dalama. Parasites were extensively detected in September and March. The analysis indicated that collected ticks were infected with different Anaplasma/Ehrlichia species. PMID- 26809917 TI - [Investigation of the Risk Factors Affecting Toxoplasma gondii Seropositivity in Women of Reproductive Age Applying to the Maternity Clinic of Kilis State Hospital]. AB - OBJECTIVE: The objective of the study is to detect the seroprevalence of toxoplasmosis in Kilis province, determine the risk factors for toxoplasmosis, and assess the effect of risk factors on seropositivity. METHODS: The research performed in Kilis State Hospital was a cross-sectional study in which Enzyme linked Immunosorbent Assay (ELISA) was used. The study included women between the ages of 15 and 49 years. The number of samples was 322. Female patients participating had to fill a questionnaire form of 27 questions in total, and blood samples were taken. Survey and laboratory results were uploaded to SPSS 15 program and assessed. RESULTS: As results of the study, the seropositivity of anti-Toxoplasma gondii (anti-T. gondii) Immunoglobulin G (IgG) antibodies was determined to be 63.4% and that of anti-T. gondii Immunoglobulin M (IgM) antibodies was determined to be 4.0%. It was found that the seropositivity of anti-T. gondii IgG antibodies was significantly dependent on age groups, educational status, number of live births, and habits of raw or undercooked meat consumption. It was found that the IgM seroprevalence in 210 pregnant women was 3.8%, and the IgG seroprevalence was positive at 59.5%; no statistical significance could be determined in both. CONCLUSION: It was determined that age distribution, income and educational levels, and eating habits of people living in the research region affect toxoplasmosis. PMID- 26809918 TI - Comparing the Efficacy of Commercially Available Insecticide and Dimeticone based Solutions on Head Lice, Pediculus capitis: in vitro Trials. AB - OBJECTIVE: Head lice infestation is a public health and social problem for almost all countries worldwide. For its treatment, insecticide and dimeticone-based solutions are currently available in the markets in many countries. We aimed to compare the efficacy of commercially available anti-head lice shampoos containing insecticide and physically effective products with different percentages of dimeticone using an in vitro technique. METHODS: Head lice specimens were collected from primary school children using special plastic and metal combs. Anti-head lice products were commercially purchased and used directly. The specimens were placed one by one in 5-cm Petri dishes containing a slightly wet filter paper and were kept in a plastic cage at 28+/-2 degrees C and 50%+/-20% relative humidity. A standardized protocol was used for testing all the products, and mortality data were obtained after 24 h. Two control tests were performed with each batch of trials. For each product and control, 10-20 head lice specimens were used, and the results were statistically analyzed. RESULTS: Our study demonstrated that among all the tested products, two products containing mineral oils [5.5% dimeticone & silicone (patented product) and dimeticone (no percentage mentioned in the prospectus) & cyclopentasiloxane] were found to be more effective for killing head lice in vitro. CONCLUSION: Physically effective products can be repetitively used because they are non-toxic and resistance to them is not expected. To control the infestation at a public level, the use of these products needs to be encouraged with respect to their cost price. PMID- 26809919 TI - [Retrobulbar Hydatid Cyst: A Case Report]. AB - Hydatid cyst is an infectious disease caused by Echinococcus granulosus, transmitted by dogs and encountered mostly in liver and lungs. As the central nervous system involvement is considered, retrobulbar disease is seen pretty rarely. In this subject; a patient complaining from an impaired vision diagnosed as hydatid cyst disease via radiological imagings and histopathological findings. PMID- 26809920 TI - First case of Trichodectes pinguis (Phthiraptera: Ischnocera: Trichodectidae) on a Bear (Ursus arctos) in Turkey. AB - This study was conducted to provide morphological characters of Trichodectes pinguis Burmeister, 1838 that was found on a European brown bear (Ursus arctos Linnaeus) that was found injured in the Van province, eastern Turkey. Three lice specimens were collected from the bear, and they were identified as T. pinguis. The morphological characteristics of this species were provided in this study. T. pinguis was reported for the first time in Turkey. PMID- 26809921 TI - [Urogenital Myiasis Caused by Psychoda albipennis (Diptera: Psychodidae) in a Woman in Siirt]. AB - Urogenital myiasis cases occurring with the settlement of larvae of flies belonging to the order Diptera are facultative and are rarely encountered in humans. In this study, urogenital myiasis caused by Psychoda albipennis in a 20 year-old female patient was presented. The patient was admitted to our hospital with complaints of nausea, vomiting, and dysuria and claimed that she saw motile larvae in her urine. Five larvae collected from the patient's urine were microscopically examined, and they were identified as fourth-stage larvae of Psychoda albipennis. Complaints of the patient ceased after the application of an antibiotic and urinary antiseptic. It was concluded that myiasis should be considered in patients with urogenital complaints. PMID- 26809922 TI - [Four Hydatid Cysts in One Family: Is Family Screening Necessary?]. AB - Hydatid cyst is a parasitic infection mostly caused by Echinococcus granulosus. As transmission occurs from infected dogs, it is endemic in animal husbandry regions. Here four patients within the same family are presented. The first patient is a 10 year-old girl admitted with nausea, vomiting, and fever. On her physical examination, there were decreased respiratory sounds in the right lung, rales, and hepatomegaly. In the radiological examination, cysts were seen in both her lung and liver. After the confirmation of the diagnosis with a serological examination, surgical resection was performed, and albendazole treatment was given. On family screening, cysts were detected in the liver and spleen in her asymptomatic 6-year-old brother; in the lung, liver, spleen, and right kidney in her 33-year-old mother who had repeating abdominal pain; and in the liver and left kidney in her 33-year-old asymptomatic father. Hydatid cyst infection was serologically confirmed in all patients, and they were given albendazole and were surgically treated. In this case report, four patients in the same family and diagnosed as having hydatid cysts were presented. It was emphasized that once a hydatid cyst was diagnosed, family screening became important, in endemic regions in particular. PMID- 26809923 TI - An Unusual Cause of Bleeding on the Floor of Mouth: Leech Infestation. AB - Leech infestation is a very rare phenomenon in humans. It mostly occurs in humans when rural untreated water is drunk or while swimming in streams or lakes. When leeches adhere to the mucous membrane, they ingest blood. Thus, they can sometimes cause severe anemia that may require blood transfusion. We report a case that was referred to emergency service with bleeding in the floor of the mouth. A 10-year-old child was referred to the emergency service of a city hospital with a complaint of swelling in the floor of the mouth and spitting of blood. The patient was promptly taken to the operating room. Using local anesthesia, a surgical incision was made, and a moving, dark brown foreign body was removed from the floor of the mouth and identified as a leech. Leech endoparasitism should be considered as a cause of unexplained anemia due to bleeding from the throat. Accordingly, leech infestation must be considered in differential diagnosis when a patient complains of spitting of blood, hoarseness, or dysphagia. PMID- 26809924 TI - Approach to Fever in Sub-Saharan Tropical Africa. PMID- 26809925 TI - Genome-wide identification of copy number variation using high-density single nucleotide polymorphism array in Japanese Black cattle. AB - BACKGROUND: Copy number variation (CNV) is an important source of genetic variability associated with phenotypic variation and disease susceptibility. Comprehensive genome-wide CNV maps provide valuable information for genetic and functional studies. To identify CNV in Japanese Black cattle, we performed a genome-wide autosomal screen using genomic data from 1,481 animals analyzed with the Illumina Bovine High-Density (HD) BeadChip Array (735,293 single-nucleotide polymorphisms (SNPs) with an average marker interval of 3.4 kb on the autosomes). RESULTS: We identified a total of 861 CNV regions (CNVRs) across all autosomes, which covered 43.65 Mb of the UMD3.1 genome assembly and corresponded to 1.74% of the 29 bovine autosomes. Overall, 35% of the CNVRs were present at a frequency of > 1% in 1,481 animals. The estimated lengths of CNVRs ranged from 1.1 kb to 1.4 Mb, with an average of 50.7 kb. The average number of CNVR events per animal was 35. Comparisons with previously reported cattle CNV showed that 72% of the CNVR calls detected in this study were within or overlapped with known CNVRs. Experimentally, three CNVRs were validated using quantitative PCR, and one CNVR was validated using PCR with flanking primers for the deleted region. Out of the 861 CNVRs, 390 contained 717 Ensembl-annotated genes significantly enriched for stimulus response, cellular defense response, and immune response in the Gene Ontology (GO) database. To associate genes contained in CNVRs with phenotypes, we converted 560 bovine Ensembl gene IDs to their 438 orthologous associated mouse gene IDs, and 195 of these mouse orthologous genes were categorized into 1,627 phenotypes in the Mouse Genome Informatics (MGI) database. CONCLUSIONS: We identified 861 CNVRs in 1,481 Japanese Black cattle using the Illumina BovineHD BeadChip Array. The genes contained in CNVRs were characterized using GO analysis and the mouse orthologous genes were characterized using the MGI database. The comprehensive genome-wide CNVRs map will facilitate identification of genetic variation and disease-susceptibility alleles in Japanese Black cattle. PMID- 26809926 TI - In-hospital mortality due to pulmonary embolism in patients with Alzheimer disease: a sex effect? PMID- 26809927 TI - Outcomes of non-STEMI patients transported by emergency medical services vs private vehicle. AB - BACKGROUND: Non-ST-segment elevation myocardial infarctions (NSTEMIs) are more common but less studied than ST-segment elevation myocardial infarctions (STEMIs) treated by emergency medical services (EMS). OBJECTIVE: The purpose of this study was to evaluate the differences in baseline characteristics and outcomes of NSTEMI patients when arriving by EMS vs self-transport. METHODS: We performed a retrospective medical record review of 96 EMS patients and 96 self-transport patients with the diagnosis of NSTEMI based on billing code. RESULTS: The mean age of patients arriving by EMS was 75 vs 65 years for self-transport patients (P<= .000). Patients arriving by self-transport received cardiac catheterization more often than patients arriving by EMS (84% vs 49%, P<= .001). Emergency medical services patients had significantly longer average hospital length of stay and intensive care unit length of stay than did patients arriving by self transport (6.5 vs 4 days [P<= .001] and 4.1 vs 2.7 days [P= .019]). Significantly more EMS patients were discharged to a new extended care facility (25% vs 3.1%, P<= .001). Finally, more EMS patients died in the hospital (18.8 vs 4.2%, P= .002). CONCLUSIONS: Patients with NSTEMI who arrived by EMS are older, are more ill, and have worse outcomes compared with patients who arrived by self transport. Further research into patient reasoning for mode of transportation to the ED may influence public health interventions, public policy development, and EMS and hospital protocols for management of NSTEMIs. The high mortality in prehospital cohort should prompt further investigation to develop evidence-based protocols. PMID- 26809928 TI - Ultrasound-guided nerve blocks for intracapsular and extracapsular hip fractures. AB - OBJECTIVES: To compare pain relief between patients with intracapsular and extracapsular hip fractures who received an ultrasound-guided femoral nerve block (USFNB). DESIGN: A multicenter, prospective, randomized, clinical trial. SETTING: The study was conducted in the emergency departments of 3 academic hospitals located in New York City. SUBJECTS: Patients aged >=60 years presenting to the emergency department with hip fracture. METHODS: A subgroup analysis from a larger data set was conducted of patients with intracapsular and extracapsular hip fractures who received an USFNB. We compared pain scores at baseline and then at 2 and 3 hours after the nerve block was performed, and also assessed pain relief at 2 and 3 hours. RESULTS: Seventy-seven patients were randomized to receive USFNB, of which 68 had follow-up data at 2 and 3 hours and were included in the data analysis. Thirty-one were diagnosed with intracapsular and 37 with extracapsular hip fractures. In both groups, reductions in pain scores were clinically and statistically significant. In the intracapsular group, mean pain scores decreased from 6.23 to 3.81 (P < .0001) at 2 hours and from 6.23 to 3.87 (P < .0001) at 3 hours. In the extracapsular group, mean pain scores decreased from 6.62 to 3.89 (P < .0001) at 2 hours and from 6.62 to 3.46 (P < .0001) at 3 hours. These differences were similar between the extracapsular and intracapsular groups at 2 hours (P = .92) and at 3 hours (P = .58), thus demonstrating similar reductions in pain in the 2 groups. The differences in pain relief between the intracapsular and extracapsular groups were also similar: 1.61 (confidence interval [CI], 1.14-2.08) vs 1.35 (CI, 0.96-1.75) at 2 hours (P = .39) and 1.68 (CI, 1.21-2.15) vs 1.38 (CI, 0.89-1.87) at 3 hours (P = .38). CONCLUSION: Ultrasound-guided femoral nerve block was equally effective in reducing pain for patients with both intracapsular and extracapsular hip fractures. PMID- 26809929 TI - Ketamine-propofol combination (ketofol) vs propofol for procedural sedation and analgesia: systematic review and meta-analysis. AB - OBJECTIVE: This meta-analysis of trials was conducted to evaluate the analgesic and side effects of ketamine-propofol combination (ketofol) in comparison to propofol in procedural sedation and analgesia (PSA). METHODS: Medline, EMBASE, Scopus, CINHAL, and Cochrane Central Register of Controlled Trials were searched for clinical trial. The administration complications were the key outcomes of interest. RESULT: Eighteen clinical trials that met our criteria were included in the analysis. Pooling of data showed that ketofol is significantly effective for reduction of respiratory complication and with relative risk (RR) of 0.31 in 14 trials (95% confidence interval [CI], 0.47-0.7; P = .001). Ketofol was also effective in reducing cardiovascular complications with hypotension RR of 0.11 in 9 trials (95% CI, 0.17-0.97; P = .04) and bradycardia RR of 0.47 in 8 trials (95% CI, 0.28-0.72; P = .008). The present study also showed that the summary of RR for psychomimetic complications was 1.95 in 13 trials were (95% CI, 0.79-4.81; P = .15) and for muscle rigidity was 0.52 for 2 trials (95% CI, 0.06-4.67; P = .56), and both were insignificant. In regard to nausea and vomiting, the RR was 1.23 in 12 trials (95% CI, 0.39-3.88; P = .72) and insignificant. CONCLUSION: This meta-analysis demonstrates good safety profile in cardiorespiratory problems and comparable rate of other complications with propofol in adult procedural sedation and analgesia. PMID- 26809930 TI - Hypersensitivity reaction after administration of rivaroxaban (Xarelto). AB - Little has been documented regarding hypersensitivity reactions with rivaroxaban or other factor Xa inhibitors. We report the development of a hypersensitivity reaction to rivaroxaban in a 64-year-old African American male patient who presented to the emergency department and was subsequently evaluated in dermatology consultation and follow-up. This case highlights the vigilance required by health care workers in recognizing potential adverse effects of newer anticoagulation therapy and in making medication changes where necessary. PMID- 26809931 TI - Hepatitis C virus infection in the 1945-1965 birth cohort (baby boomers) in a large urban ED. AB - INTRODUCTION: The US Preventive Services Task Force recommends one-time screening of the 1945-1965 birth cohort (baby boomers) for hepatitis C (HCV) infection. New York State legislation mandates screening of baby boomers for HCV in most patient care settings except the emergency department (ED). This cross-sectional study explores baby boomer knowledge of HCV, prevalence of HCV infection, and linkage to care from a large urban ED. METHOD: Patients participated in a researcher administered structured interview and were offered an HCV screening test. If HCV antibody reactive, a follow-up clinic appointment was made within 6 weeks. Reminder telephone calls were made a week before the appointment. Attendance at the follow-up appointment was considered successful linkage to care. RESULTS: A total of 915 eligible patients were approached between October 21, 2014, and July 13, 2015. A total of 427 patients participated in the structured interview; 383 agreed to an HCV rapid test. Prevalence of HCV antibody reactivity was 7.3%. Four patients were successfully linked to care. General knowledge about HCV was fair. Misconceptions about transmission were apparent. Beliefs that "if someone is infected with HCV they will most likely carry the virus all their lives unless treated" and that "someone with hepatitis can look and feel fine" were significantly associated with agreement to testing. CONCLUSIONS: Better linkage to care is needed to justify HCV screening in the 1945-1965 birth cohort in this particular ED setting. Linkage to care from the ED is challenging but can potentially be improved with specific measures including simplified screening algorithms and supportive resources. PMID- 26809932 TI - Long-term purification efficiency of a wetland constructed to treat runoff from peat extraction. AB - Peat extraction increases the phosphorus, nitrogen, organic matter, suspended solids, and iron concentrations in runoff, resulting in negative effects on downstream water bodies. Wetlands are commonly used as natural cost-effective solutions to mitigate these negative effects. This study analyzed changes in the quality of runoff water from peat extraction areas and the long-term efficiency of constructed wetlands. The results indicate that the quality of runoff water changed after the initial drainage and during peat extraction. Nitrogen leached at high concentrations in the early stages of peat extraction following drainage, whereas the leaching of iron and phosphorus increased after peat extraction from deeper layers. Comparison of water quality and impurities retained immediately after treatment wetland construction and 14 years later showed that the treatment wetland remained functional, with good retention capacity, over a long period. PMID- 26809933 TI - Accessing methadone within Moldovan prisons: Prejudice and myths amplified by peers. PMID- 26809934 TI - Conspicuous by their abstinence: The limited engagement of heroin users in English and Welsh Drug Recovery Wings. AB - BACKGROUND: In recent years, an abstinence-focused, 'recovery' agenda has emerged in UK drug policy, largely in response to the perception that many opioid users had been 'parked indefinitely' on opioid substitution therapy (OST). The introduction of ten pilot 'Drug Recovery Wings' (DRWs) in 2011 represents the application of this recovery agenda to prisons. This paper describes the DRWs' operational models, the place of opiate dependent prisoners within them, and the challenges of delivering 'recovery' in prison. METHODS: In 2013, the implementation and operational models of all ten pilot DRWs were rapidly assessed. Up to three days were spent in each DRW, undertaking semi-structured interviews with a sample of 94 DRW staff and 102 DRW residents. Interviews were fully transcribed, and coded using grounded theory. Findings from the nine adult prisons are presented here. RESULTS: Four types of DRW were identified, distinguished by their size and selection criteria. Strikingly, no mid- or large sized units regularly supported OST recipients through detoxification. Type A were large units whose residents were mostly on OST with long criminal records and few social or personal resources. Detoxification was rare, and medication reduction slow. Type B's mid-sized DRW was developed as a psychosocial support service for OST clients seeking detoxification. However, staff struggled to find such prisoners, and detoxification again proved rare. Type C DRWs focused on abstinence from all drugs, including OST. Though OST clients were not intentionally excluded, very few applied to these wings. Only Type D DRWs, offering intensive treatment on very small wings, regularly recruited OST recipients into abstinence-focused interventions. CONCLUSION: Prison units wishing to support OST recipients in making greater progress towards abstinence may need to be small, intensive and take a stepped approach based on preparatory motivational work and extensive preparation for release. However, concerns about post-release deaths will remain. PMID- 26809935 TI - When is it OK to be drunk? Situational and cultural variations in the acceptability of visible intoxication in the UK and Norway. AB - BACKGROUND: Research on norms regulating drunken behaviour has tended to focus on differences between different countries and cultures rather than variations within them. Here, we examine whether there are: (i) situation-specific differences in the acceptability of visible intoxication among students in the UK and Norway; (ii) whether there are situation-specific and overall differences in this regard between the two countries; and finally (iii) to what degree possible differences reflect individual characteristics such as use of alcohol, perceived harm of alcohol consumption, and broader value orientation. METHODS: Students at one British (n=473) and one Norwegian (n=472) university responded to a survey including a battery of questions assessing the acceptability of visible intoxication in different situations, such as with friends, with work colleagues, with family members, and situations where children are present. Data were also collected regarding alcohol consumption, perceived harms of alcohol consumption, and value orientation. Analyses of covariance were performed to assess patterns in the acceptability of visible intoxication across different situations, and the relative contributions of country, alcohol consumption, perceived harm of alcohol consumption and human values. RESULTS: In both countries, visible intoxication was rated as most acceptable in situations involving friends and colleagues. Students from both countries rated visible intoxication least acceptable in situations where children are present. However, both overall, and in situations where children or family members are present, acceptability of visible intoxication scores were higher in the UK than Norway. These differences persisted after control for other variables. CONCLUSION: The study demonstrates large situational variation in acceptability of drunken behaviour, pointing to a fine-meshed set of norms regulating alcohol use and drunken behaviour within the two cultures, with the UK standing out as a more alcohol-liberal culture than Norway. Such differences underline how norms regulating drunken behaviour are culturally constituted. PMID- 26809937 TI - Finding a Human Leukocyte Antigen Match -- A Perfect Stranger. PMID- 26809936 TI - Racial disparities in patient activation: Evaluating the mediating role of health literacy with path analyses. AB - OBJECTIVE: The aim of this study was to use path analysis methods to determine if health literacy mediates the relationship between race and patient activation. METHODS: We performed a secondary analysis of data from a randomized controlled trial in elderly, urban, minority patients using path analysis. Path analysis was used to evaluate the mediation of race on patient activation through different variables. Several models were tested for best fit for their effects on patient activation. RESULTS: Across all models, significant mediation paths were identified from race to lower patient activation through health literacy. This relationship remained significant throughout alternative model testing for covariate combinations. The best-fit model included an indirect effect of sex on patient activation through health literacy indicating that the mediation effect of health literacy on patient activation was most profound for African American males. Health literacy had a bigger influence on patient activation for participants with a greater comorbidity than for those with fewer conditions. No significant direct effect was shown between race and patient activation in any of the models. CONCLUSION: Racial disparities in patient activation were fully mediated by health literacy skills. PRACTICE IMPLICATIONS: Future interventions to improve racial disparities in patient activation need to be targeted at improving health literacy. PMID- 26809939 TI - Tolerability of 2 doses of pandemic influenza vaccine (Focetria(r)) and of a prior dose of seasonal 2009-2010 influenza vaccination in the Netherlands. AB - In the Netherlands, people indicated for seasonal influenza vaccination are divided in 3 risk groups, i.e. those less than 60 y (y) with comorbidity and those 60 y and over with and without comorbidity. Those risk groups were also eligible for pandemic vaccination during the 2009 influenza A(H1N1) pandemic. We assessed tolerability of seasonal influenza vaccination and 2 doses of pandemic influenza A(H1N1) vaccine, adjuvanted with MF-59, administered 2 and 5 weeks after seasonal 2009-2010 vaccination among adults. Vaccinees were asked to return questionnaires on local and systemic adverse events (AEs) after each of 3 consecutive vaccinations given at the office of their General Practitioner. Sex- and risk group-specific AE-frequencies were calculated. Generalized Linear Mixed Model with seasonal vaccination as reference was used to calculate odds ratios (ORs) for AEs of the 2 pandemic doses. 5553 questionnaires (3251 vaccinees) were returned. Vaccinees reported any local AE after seasonal vaccination and both pandemic doses in 34%, 23%, and 18%, respectively. These percentages were 29%, 25%, and 16% for any systemic AE. Men reported fewer local and systemic AEs then women (p<0.0001). The risk of local (OR range 0.34-0.63) and systemic (OR range 0.39-0.99) AEs (overall, stratified by risk group and by sex) was lower after both pandemic doses compared to seasonal vaccination. This decreased risk was more pronounced after the second pandemic dose than after the first. Therefore, we conclude that MF59-adjuvanted pandemic vaccine given after seasonal vaccination was well tolerated. PMID- 26809940 TI - Management of bone mineral density in HIV-infected patients. AB - INTRODUCTION: Loss of bone mineral density is an emerging problem in persons living with HIV infection. Earlier and more rapid bone demineralization has been attributed not only to the high prevalence of traditional risk factors, but also to specific HIV-related factors. The aim of this guidance is to stimulate an appropriate management of osteoporosis in this population, to identify patients at risk and to better manage them. AREAS COVERED: Appropriate screening of HIV infected subjects to identify those at risk for bone fractures is described, as well as the recommended interventions. American and European recommendations in HIV-infected and non-infected populations were considered. As the etiology of bone loss is multifactorial, many factors have to be addressed. Overall, recommendations on traditional risk factors are the same for HIV-infected and non HIV-infected subjects. However, we should consider some specific factors in the HIV-infected population, including an appropriate antiretroviral therapy in patients with low bone mineral density, and probably novel strategies that could provide an additional benefit, such as anti-inflammatory drugs, although data supporting this approach are scant. EXPERT OPINION: Some personal opinions are highlighted on the management of bone health in HIV-infected subjects, mainly on the use of FRAX((r)) score and DXA scans. In addition, the need to implement new strategies to delay demineralization is remarked upon. PMID- 26809942 TI - Stereospecific Synthesis of Tri- and Tetrasubstituted alpha-Fluoroacrylates by Mizoroki-Heck Reaction. AB - Ligand-free, efficient, palladium-catalyzed Mizoroki-Heck reaction between methyl alpha-fluoroacrylate and arene or hetarene iodides is reported for the first time. The reaction is stereospecific and provides fair to quantitative yields of fluoroalkenes. The Mizoroki-Heck reaction starting from more hindered and usually reluctant trisubstituted acrylate, to access tetrasubstituted fluoroalkenes, is also reported. Finally, the use of a three-step synthesis sequence, including Mizoroki-Heck reaction, allows the synthesis of fluorinated analogues of therapeutic agents with high yield. PMID- 26809941 TI - Addressing barriers to the prevention, diagnosis and treatment of hepatitis B and C in the face of persisting fiscal constraints in Europe: report from a high level conference. AB - In the WHO-EURO region, around 28 million people are currently living with chronic viral hepatitis, and 120,000 people die every year because of it. Lack of awareness and understanding combined with the social stigma and discrimination exacerbate barriers related to access to prevention, diagnosis and treatment services for those most in need. In addition, the persisting economic crisis has impacted on public health spending, thus posing challenges on the sustainable investment in promotion, primary and secondary prevention, diagnosis and treatment of viral hepatitis across European countries. The Hepatitis B and C Public Policy Association in cooperation with the Hellenic Center for Disease Prevention and Control together with 10 partner organizations discussed at the Athens High Level Meeting held in June 2014 recent policy developments, persisting and emerging challenges related to the prevention and management of viral hepatitis and the need for a de minimis framework of urgent priorities for action, reflected in a Call to Action (Appendix S1). The discussion confirmed that persisting barriers do not allow the full realisation of the public health potential of diagnosing and preventing hepatitis B and C, treating hepatitis B and curing hepatitis C. Such barriers are related to (a) lack of evidence-based knowledge of hepatitis B and C, (b) limited access to prevention, diagnosis and treatment services with poor patient pathways, (c) declining resources and (d) the presence of social stigma and discrimination. The discussion also confirmed the emerging importance of fiscal constraints on the ability of policymakers to adequately address viral hepatitis challenges, particularly through increasing coverage of newer therapies. In Europe, it is critical that public policy bodies urgently agree on a conceptual framework for addressing the existing and emerging barriers to managing viral hepatitis. Such a framework would ensure all health systems share a common understanding of definitions and indicators and look to integrate their responses to manage policy spillovers in the most cost-effective manner, while forging wide partnerships to sustainably and successfully address viral hepatitis. PMID- 26809943 TI - Circulating serovars of Leptospira in cart horses of central and southern Ethiopia and associated risk factors. AB - Little work has been done on diseases of horses in Ethiopia or tropical regions of the world. Yet, Ethiopia has the largest horse population in Africa and their horses play a pivotal role in their economy as traction animals. A serological and questionnaire survey was therefore conducted to determine the circulating serovars of Leptospira and their association with potential risk factors in the cart horse population of Central and Southern Ethiopia. A total of 184 out of 418 cart horses from 13 districts had antibody titres of 1:100 or greater to at least one of 16 serovars of Leptospira species in Central and Southern Ethiopian horses. A significantly higher seropositivity (62.1%) was noted in horses from the highland agroecology followed by midland (44.4%) and lowland (39.8%). Serovar Bratislava (34.5%) was the predominant serovar followed by serovars Djasiman (9.8%), Topaz (5.98%) and Pomona (5.3%). Age and location proved to be associated with seropositive horses with older horses being more commonly affected and the districts of Ziway (Batu) (Apparent Prevalence (AP)=65.5%), Shashemene (AP=48.3%) and Sebeta (AP=41.4%) having the highest prevalence. Multivariable logistic regression found risk factors significantly associated with Leptospira seropositive horses were drinking river water (OR=2.8) and horses 7-12 years old (OR=5) and risk factors specifically associated with serovar Bratislava seropositive horses were drinking river water (OR=2.5), horses >=13 years (OR=3.5) and the presence of dogs in adjacent neighbouring properties (OR=0.3). Dogs had a protective effect against seropositivity to serovars Bratislava and Djasiman, which may be due to their ability to control rodents. The high seroprevalence confirm that leptospirosis is endemic among horses of Central and Southern Ethiopia. The predominance of serovar Bratislava supports the idea that serovar Bratislava may be adapted to and maintained by the horse population of Central and Southern Ethiopia. This study emphasizes the need for further countrywide serological surveys and isolation of circulating leptospires in animals and humans in order to understand the role of horses in the epidemiology of this disease. PMID- 26809944 TI - The Grand Divergence in Global Child Health: Confronting Data Requirements in Areas of Conflict and Chronic Political Instability. PMID- 26809945 TI - A demonstration of how to do a meta-analysis that combines single-case designs with between-groups experiments: The effects of choice making on challenging behaviors performed by people with disabilities. AB - OBJECTIVE: This paper demonstrates how to conduct a meta-analysis that includes both between-group and single-case design (SCD) studies. The example studies whether choice-making interventions decrease challenging behaviors performed by people with disabilities. METHODS: We used a between-case d-statistic to conduct a meta-analysis of 15 between-group and SCD studies of 70 people with a disability, who received a choice intervention or control. We used robust variance estimation to adjust for dependencies caused by multiple effect sizes per study, and conducted moderator, sensitivity, influence, and publication bias analyses. RESULTS: The random-effects average was d = 1.02 (standard error of 0.168), so the 95% confidence interval (CI) suggests choice-making reduces challenging behaviors by 0.65 to 1.38 standard deviations. Studies that provided choice training produced a significantly larger intervention effect. CONCLUSION: Choice-making reduces challenging behaviors performed by people with disabilities. PMID- 26809946 TI - n-3 Fatty acids and asthma. AB - Asthma is one of the most common and prevalent problems worldwide affecting over 300 million individuals. There is some evidence from observational and intervention studies to suggest a beneficial effect of n-3 PUFA in inflammatory diseases, specifically asthma. Marine-based n-3 PUFA have therefore been proposed as a possible complementary/alternative therapy for asthma. The proposed anti inflammatory effects of n-3 fatty acids may be linked to a change in cell membrane composition. This altered membrane composition following n-3 fatty acid supplementation (primarily EPA and DHA) can modify lipid mediator generation via the production of eicosanoids with a reduced inflammatory potential/impact. A recently identified group of lipid mediators derived from EPA including E-series resolvins are proposed to be important in the resolution of inflammation. Reduced inflammation attenuates the severity of asthma including symptoms (dyspnoea) and exerts a bronchodilatory effect. There have been no major health side effects reported with the dietary supplementation of n-3 fatty acids or their mediators; consequently supplementing with n-3 fatty acids is an attractive non pharmacological intervention which may benefit asthma. PMID- 26809947 TI - Electronic discharge summary and prescription: improving communication between hospital and primary care. AB - BACKGROUND: The discharge letter is a key component of the communication pathway between the hospital and primary care. Accuracy and timeliness of delivery are crucial to ensure continuity of patient care. Electronic discharge summaries (EDS) and prescriptions have been shown to improve quality of discharge information for general practitioners (GPs). The aim of this study was to evaluate the effect of a new EDS on GP satisfaction levels and accuracy of discharge diagnosis. METHODS: A GP survey was carried out whereby semi-structured interviews were conducted with 13 GPs from three primary care centres who receive a high volume of discharge letters from the hospital. A chart review was carried out on 90 charts to compare accuracy of ICD-10 coding of Non-Consultant Hospital Doctors (NCHDs) with that of trained Hopital In-Patient Enquiry (HIPE) coders. RESULTS: GP satisfaction levels were over 90 % with most aspects of the EDS, including amount of information (97 %), accuracy (95 %), GP information and follow-up (97 %) and medications (91 %). 70 % of GPs received the EDS within 2 weeks. ICD-10 coding of discharge diagnosis by NCHDs had an accuracy of 33 %, compared with 95.6 % when done by trained coders (p < 0.00001). CONCLUSION: The introduction of the EDS and prescription has led to improved quality of timeliness of communication with primary care. It has led to a very high satisfaction rating with GPs. ICD-10 coding was found to be grossly inaccurate when carried out by NCHDs and it is more appropriate for this task to be carried out by trained coders. PMID- 26809948 TI - PEGylated Albumin-Based Polyion Complex Micelles for Protein Delivery. AB - An increasing amount of therapeutic agents are based on proteins. However, proteins as drug have intrinsic problems such as their low hydrolytic stability. Delivery of proteins using nanoparticles has increasingly been the focus of interest with polyion complex micelles, prepared from charged block copolymer and the oppositely charged protein, as an example of an attractive carrier for proteins. Inspired by this approach, a more biocompatible pathway has been developed here, which replaces the charged synthetic polymer with an abundant protein, such as albumin. Although bovine serum albumin (BSA) was observed to form complexes with positively charged proteins directly, the resulting protein nanoparticle were not stable and aggregated to large precipitates over the course of a day. Therefore, maleimide functionalized poly(oligo (ethylene glycol) methyl ether methacrylate) (MI-POEGMEMA) (Mn = 26000 g/mol) was synthesized to generate a polymer-albumin conjugate, which was able to condense positively charged proteins, here lysozyme (Lyz) as a model. The PEGylated albumin polyion complex micelle with lysozyme led to nanoparticles between 15 and 25 nm in size depending on the BSA to Lyz ratio. The activity of the encapsulated protein was tested using Sprouty 1 (C-12; Spry1) proteins, which can act as an endogenous angiogenesis inhibitor. Condensation of Spry1 with the PEGylated albumin could improve the anticancer efficacy of Spry1 against the breast cancer cells lowering the IC50 value of the protein. Furthermore, the high anticancer efficacy of the POEGMEMA-BSA/Spry1 complex micelle was verified by effectively inhibiting the growth of three-dimensional MCF-7 multicellular tumor spheroids. The PEGylated albumin complex micelle has great potential as a drug delivery vehicle for a new generation of cancer pharmaceuticals. PMID- 26809949 TI - Risk factors related to recurrent suicide attempts in patients with self inflicted wrist injuries. PMID- 26809950 TI - Brazilian Portuguese version of the Short Mood and Feelings Questionnaire (SMFQ) for screening children and adolescents seeking plastic surgery. PMID- 26809951 TI - Fractional anisotropy in the supplementary motor area correlates with disease duration and severity of amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is progressive and fatal neurodegenerative disorder with upper and lower motor neuron signs. There are no biomarkers to track disease progression. To address this issue, we investigated regions in which fractional anisotropy (FA) values derived from diffusion weighted images correlated with both disease severity and duration in ALS patients. Fourteen patients with ALS were enrolled in this study. Voxel-based analysis revealed volume of interests (VOIs) showing significant correlation. Finally, Spearman rank correlation coefficient was assessed between FA value in each VOI and disease severity or duration. In the VOI of left supplementary motor area (SMA), FA value significantly correlated with disease severity and duration both (disease severity, rho = 0.59, p = 0.025; disease duration, rho = -0.69, p = 0.006). The present finding suggested the possibility that the abnormality in motor-related region including SMA could be a candidate for a biomarker to track disease progression. PMID- 26809952 TI - Rapid versus slow withdrawal of antiepileptic monotherapy in 2-year seizure-free adult patients with epilepsy (RASLOW) study: a pragmatic multicentre, prospective, randomized, controlled study. AB - Antiepileptic drug withdrawal may be an option for patients who have been seizure free for some years. The best withdrawal rate is questionable; in particular, it is unknown whether "rapid" withdrawal is associated with a higher risk of relapse as compared to "slow" withdrawal. We aim to establish if a slow or a rapid withdrawal schedule of antiepileptic monotherapy influences relapse rate in adult patients with focal or generalized epilepsy who have been seizure free for at least 2 years. This multicentre, prospective, randomized controlled study will enroll adult patients with focal or generalized epilepsy, who are seizure free on monotherapy. Patients will be randomized to a slow (160 days) or a rapid (60 days) schedule. Follow-up will last 1 year after randomization. The primary endpoint is the time to seizure relapse; secondary endpoints are compliance to the assigned schedule, occurrence of status epilepticus, of seizure-related injuries and mortality. A sample size of 350 patients has been planned. Univariate and multivariate analysis by Kaplan-Meier curves and Cox regression (primary endpoint) and by logistic regression (secondary endpoint) will be performed. The present study should contribute to better define the best withdrawal period for AED treatment in adult patients with epilepsy. PMID- 26809953 TI - Topiramate-induced paresthesia is more frequently reported by migraine than epileptic patients. AB - Topiramate is an approved and effective drug in migraine prophylaxis. Paresthesia is the most commonly reported side effect. The primary objective of this study was to compare the frequency of topiramate-induced paresthesia in migraine headache to epileptic patients. Patients with migraine without aura and epilepsy were enrolled in this observational study. All cases were interviewed by telephone about their history of paresthesia. Confounding factors were controlled through logistic regression. The odds ratio of developing topiramate-induced paresthesia in migraine compared to epilepsy patients was 3.4. Three factors were independent contributors to developing topiramate-induced paresthesia: female sex (odds ratio 2.1), topiramate dosage (odds ratio 0.3) and duration of therapy. Our findings indicate an independent association between migraine and development of paresthesia. Migraineurs were more likely than epileptic patients to report paresthesia as topiramate adverse effects. Female sex, treatment duration and topiramate dosage contribute significantly to subsequent development of paresthesia. PMID- 26809954 TI - Effects of Acute Stroke Serum on Non-Ischemic Cerebral and Mesenteric Vascular Function. AB - We investigated the effects of circulating factors in serum obtained from patients in the acute phase of different subtypes of ischemic stroke on non ischemic cerebral and mesenteric arteries, as a potential mechanism involved in influencing regional perfusion and thus clinical evolution. Posterior cerebral arteries (PCAs) and mesentery arteries (MAs) isolated from Wistar Kyoto rats were perfused with serum from acute stroke patients with large vessel disease without (LVD) or with hypertension (LVD + HTN), cardioembolism with hypertension (CE + HTN), or physiologic saline as controls. Myogenic activity and nitric oxide dependent vasorelaxation were assessed after 2 h of intraluminal exposure to serum. Vascular function was differentially affected by sera. Exposure to LVD serum increased myogenic tone and produced endothelial dysfunction in both PCAs and MAs. However, CE + HTN serum increased tone and decreased smooth muscle sensitivity to NO in vessels from both vascular beds. LVD + HTN serum was associated with reduced smooth muscle sensitivity to NO in vessels from both vascular beds but increased tone only in PCAs. Inflammation and oxidative stress, determined by measurement of high sensitivity C-reactive protein, uric acid, and free 8-isoprostane, were enhanced in all the serum groups. These results demonstrate vasoactive properties of acute stroke serum related to stroke subtypes that could potentially contribute to the pathogenesis of early hemodynamic-based clinical events. PMID- 26809955 TI - Stemless shoulder arthroplasty-current results and designs. AB - Stemless shoulder arthroplasty was originally introduced in 2004 by a single manufacturer. Now, over a decade later, numerous designs are available outside the USA, but as yet, only one implant has been cleared by the Food and Drug Administration (FDA) and is available for use within the USA. Often referred to as "canal sparing," these implants are designed for metaphyseal fixation to minimize humeral bone removal, avoid intraoperative and postoperative humeral fracture complications, and to decrease morbidity associated with revision operations. Recently, the second generation of stemless arthroplasty, a convertible implant allowing use in either anatomic or reverse arthroplasty configuration, was released for use outside the USA. This paper will review the available designs, reported results, and raise potential concerns for this emerging technology. PMID- 26809956 TI - Planning software and patient-specific instruments in shoulder arthroplasty. AB - Computer planning software and patient-specific instrumentation have been investigated in multiple subspecialties of orthopedics with mixed results. Shoulder arthroplasty has evolved over the last decade with improvements in implant design and surgical instrumentation. Despite these advances, glenoid positioning in shoulder arthroplasty continues to be a difficult problem. Recent advances in three-dimensional imaging techniques and the use of computer planning software may potentially address some of the common difficulties encountered by surgeons. The addition of patient-specific instrumentation and guides provide an option for patients with significant glenoid deformity that may allow improved accuracy of glenoid component implantation compared to using standard instrumentation. Studies have reported improved positioning of the glenoid component in both anatomic and reverse total shoulder arthroplasty with patient specific instrumentation and guides. More research is needed to determine whether these improvements lead to better patient-reported outcomes or implant survival. In addition, further studies will be needed to address whether this technology is cost effective for large-scale implementation in the orthopedic community. PMID- 26809957 TI - The development and validation of the Leiden Bother and Needs Questionnaire for patients with pituitary disease: the LBNQ-Pituitary. AB - BACKGROUND: Patients report persisting impairment in quality of life (QoL) after treatment for pituitary disease. At present, there is no questionnaire to assess (a) whether patients with pituitary disease are bothered by these consequences, and (b) their needs for support. OBJECTIVE: To develop and validate a disease specific questionnaire for patients with pituitary disease which incorporates patient perceived bother related to the consequences of the disease, and their needs for support. METHODS: Items for the Leiden Bother and Needs Questionnaire for patients with pituitary disease (LBNQ-Pituitary) were formulated based on results of a recent focus group study (n = 49 items). 337 patients completed the LBNQ-Pituitary and six validated QoL questionnaires (EuroQoL-5D, SF-36, MFI-20, HADS, AcroQol, CushingQoL). Construct validity was examined by exploratory factor analysis. Reliabilities of the subscales were calculated with Cronbach's alphas, and concurrent validity was assessed by calculating Spearman's correlations between the LBNQ-Pituitary and the other measures. RESULTS: Factor analyses produced five subscales (i.e., mood problems, negative illness perceptions, issues in sexual functioning, physical and cognitive complaints, issues in social functioning) containing a total of 26 items. All factors were found to be reliable (Cronbach's alphas all >=.765), and the correlations between the dimensions of the LBNQ-Pituitary and other questionnaires (all P <= .0001) demonstrated convergent validity. CONCLUSIONS: The LBNQ-Pituitary can be used to assess the degree to which patients are bothered by the consequences of the pituitary disease, as well as their needs for support. It could also facilitate an efficient assessment of patients' needs for support in clinical practice. We postulate that paying attention to needs for support will lead to optimal patient care (e.g., improvement in psychosocial care), and positively affect QoL. PMID- 26809958 TI - A comparative analysis of ESM-1 and vascular endothelial cell marker (CD34/CD105) expression on pituitary adenoma invasion. AB - OBJECTIVE: Pituitary adenomas are benign neoplasms that display invasive behavior a characteristic traditionally associated with malignancy-through an ill-defined mechanism. The role of angiogenesis-related molecules in this pathological condition remains perplexing. Our purpose is to assess the impact of endocan (endothelial cell specific molecule-1, ESM-1), CD34 and CD105 on pituitary adenoma invasion. METHODS: In this study, immunohistochemical analyses for endocan, CD34 and CD105 were performed on paraffin-embedded samples of 66 pituitary adenomas, five normal pituitaries, and five primary hepatic carcinomas. Knosp tumor grades based on magnetic resonance imaging coronal scanning were used to assess the invasiveness of each sample. The associations between endocan expression, CD34/CD105-positive microvessel densities (MVDs), and Knosp tumor invasion grades were evaluated. RESULTS: These results showed that endocan protein expression in tumor cells (TCs) was higher than that in endothelial cells (ECs) and strongly correlated with Knosp grades (P < 0.001, Spearman's r = 0.616). Moreover, while endocan-positive TCs localized around the blood vessels in adenomas with higher Knosp grades, no significant association was found between CD34/CD105-MVDs and Knosp grades (CD34: P = 0.256, r = 0.142; CD105: P = 0.183, r = 0.166). Normal pituitary seemed to exhibit lower endocan expression and contained more CD34/CD105-MVDs than pituitary adenomas. CONCLUSION: Endocan expresses in both TCs and ECs of pituitary adenoma. Endocan overexpression in TCs more accurately reflects invasiveness compared to that of CD34/CD105-MVDs and that angiogenesis may not be the primary driver of endocan-medicated pituitary adenoma invasion. PMID- 26809959 TI - Pralatrexate Monitoring Using a Commercially Available Methotrexate Assay to Avoid Potential Drug Interactions. AB - Pralatrexate (PDX) is a folate antagonist structurally similar to methotrexate (MTX). Unlike MTX, it is currently not known whether PDX exhibits delayed clearance and heightened toxicity in the setting of fluid overload. A specific serum assay for PDX is not commercially available. To our knowledge, we report the first case using an MTX serum assay as a surrogate for PDX concentrations to avoid a potential drug-drug interaction with pralatrexate. We describe a 76-year old man with refractory cutaneous T-cell lymphoma who began therapy with weekly PDX 15 mg/m(2) intravenous infusions on days 1, 8, and 15 of a 28-day cycle. He subsequently developed mucositis, a moderate right-sided pleural effusion, and peripheral edema over the next 5 weeks. Aggressive diuresis with furosemide was initiated, which was then withheld the day before his next PDX dose to avoid a potential drug-drug interaction between PDX and furosemide. His baseline MTX/PDX concentration (measured prior to administration of the cycle 2, week 2 PDX dose) was less than 0.20 MUmol/L (i.e., undetectable). After PDX administration, his 1 hour peak MTX/PDX concentration increased to 0.58 MUmol/L. Aggressive diuresis was withheld until his MTX/PDX concentration was undetectable, 43.5 hours later. PDX is more potent than MTX and displays similar pharmacokinetic properties. PDX concentrations using the serum MTX assay reflect lower values than those reported from PDX-specific assays in clinical studies. Because PDX is approved by the U.S. Food and Drug Administration for the treatment of uncommon malignancies, it is unlikely that a specific assay will be commercially developed. We propose that the MTX serum assay has merit for use in determining when to reinstate possible interacting drug therapies such as loop diuretics. PMID- 26809962 TI - ERRATUM: Role of Chemotherapy in Stage II Nasopharyngeal Carcinoma Treated with Curative Radiotherapy. AB - [This corrects the article on p. 871 in vol. 47, PMID: 25687858.]. PMID- 26809965 TI - [Cardiac arrest after epidural anesthesia for a esthetic plastic surgery: a case report]. AB - Cardiac arrest during neuraxial anesthesia is a serious adverse event, which may lead to significant neurological damage and death if not treated promptly. The associated mechanisms are neglected respiratory failure, extensive sympathetic block, local anaesthetic toxicity, total spinal block, in addition to the growing awareness of the vagal predominance as a predisposing factor. In the case reported, the patient was 25 years old, ASA I, scheduled for aesthetic lipoplasty. After sedation with midazolam and fentany, epidural anesthesia in interspaces T12-L1 and T2-T3 and catheter insertion into inferior puncture were performed. The patient remained in the supine position for 10minutes. Then, she was placed in the prone position, developing asystolic cardiac arrest 20minutes after the completion of neuraxial blockade. The medical team immediately placed the patient in the supine position and began cardiopulmonary resuscitation. Spontaneous circulation was achieved after twenty minutes of resuscitation. We discuss in this report the exacerbated vagal response as the main event mechanism. The patient's successful outcome emphasizes the importance of anaesthetic monitoring by anesthesiologists, prompt recognition and treatment of rhythm changes on the electrocardiogram. PMID- 26809960 TI - Impact of obstructive and central apneas on ventricular repolarisation: lessons learned from studies in man and pigs. AB - BACKGROUND: Sleep apnea (SA) is associated with sudden cardiac death. Compared to central apneas, obstructive apneas are associated with negative intrathoracic pressure swings inducing autonomic imbalance, which may disturb ventricular repolarisation resulting in arrhythmias. OBJECTIVES: To identify the influence of obstructive apneas versus central apneas on ventricular repolarisation. METHODS: In 14 patients with SA, duration (RT-intervals) and dispersion of ventricular repolarisation [Tpeak-to-Tend-interval (TpTe)] were determined during central apneas compared to obstructive apneas. To identify mechanisms, hypoxia alone or hypoxia with applied negative thoracic pressure was applied in a pig model for SA before and after atropine (n = 7), atenolol (n = 5) and sympathetic renal denervation (RDN, n = 7). RESULTS: In patients with SA, obstructive apneas during sleep were always associated with a prolongation of RT- as well as TpTe intervals. By contrast central apneas did not affect ventricular repolarisation significantly in the same patients. In the pig model for SA, 2 min of acute tracheal occlusion with applied negative thoracic pressure resulted in a prolongation in RT- and TpTe-interval. These changes in ventricular repolarisation could be inhibited by atenolol as well as by RDN and were not influenced by parasympathetic blockade by atropine. By contrast hypoxia alone did not affect ventricular repolarisation. CONCLUSIONS: Intrathoracic pressure swings during obstructive apneas contribute to changes in ventricular repolarisation, which are not observed with central apneas. These changes are mainly driven by sympathetic activation and may represent mechanisms for increased occurrence of sudden cardiac death in obstructive SA. PMID- 26809966 TI - [Neurolitic block of the lumbar sympathetic chain improves chronic pain in a patient with critical lower limb ischemia]. AB - BACKGROUND AND OBJECTIVES: Sympathectomy is one of the therapies used in the treatment of chronic obstructive arterial disease (COAD). Although not considered as first-line strategy, it should be considered in the management of pain difficult to control. This clinical case describes the evolution of a patient with inoperable COAD who responded properly to the lumbar sympathetic block. CASE REPORT: A female patient, afro-descendant, 69 years old, ASA II, admitted to the algology service due to refractory ischemic pain in the lower limbs. The patient had undergone several surgical procedures and conservative treatments without success. Vascular surgery considered the case as out of therapeutic possibility, unless limb amputation. At that time, sympathectomy was indicated. After admission to the operating room, the patient was monitored, positioned and sedated. The blockade was performed with the aid of radioscopy, bilaterally, at L2-L3-L4 right and L3 left levels. On the right side, at each level cited, 3mL of absolute alcohol with 0.25% bupivacaine were injected without vasoconstrictor, and on the left side only local anesthetic. The procedure was performed uneventfully. The patient was discharged with complete remission of the pain. CONCLUSION: Neurolitic block of the lumbar sympathetic chain is an effective and safe treatment option for pain control in patients with critical limb ischemia patients in whom the only possible intervention would be limb amputation. PMID- 26809967 TI - [Bezold-Jarisch reflex in a patient undergoing endoscopic sympathectomy for management of refractory angina pectoris: a case report]. AB - BACKGROUND AND OBJECTIVES: Ischemic cardiomyopathy is characterized by imbalance between supply and demand of myocardial oxygen. Endoscopic transthoracic sympathectomy is a therapeutic option indicated in refractory cases. However, the patient's position on the operating table may favor ischemic coronary events triggering the Bezold-Jarisch reflex. CASE REPORT: A female patient, 47 years old, with refractory ischemic cardiomyopathy, admitted to the operating room for endoscopic transthoracic sympathectomy, developed the Bezold-Jarisch reflex with severe bradycardia and hypotension after placement in semi-sitting position to the procedure. CONCLUSION: Bradyarrhythmia, hypotension, and asystole are complications potentially associated with patient placement in a semi-sitting position, particularly in cases with previous ischemic heart disease. PMID- 26809968 TI - Genomic organization of the zebrafish (Danio rerio) T cell receptor alpha/delta locus and analysis of expressed products. AB - In testing the hypothesis that all jawed vertebrate classes employ immunoglobulin heavy chain V (IgHV) gene segments in their T cell receptor (TCR)delta encoding loci, we found that some basic characterization was required of zebrafish TCRdelta. We began by annotating and characterizing the TCRalpha/delta locus of Danio rerio based on the most recent genome assembly, GRCz10. We identified a total of 141 theoretically functional V segments which we grouped into 41 families based upon 70 % nucleotide identity. This number represents the second greatest count of apparently functional V genes thus far described in an antigen receptor locus with the exception of cattle TCRalpha/delta. Cloning, relative quantitative PCR, and deep sequencing results corroborate that zebrafish do express TCRdelta, but these data suggest only at extremely low levels and in limited diversity in the spleens of the adult fish. While we found no evidence for IgH-TCRdelta rearrangements in this fish, by determining the locus organization we were able to suggest how the evolution of the teleost alpha/delta locus could have lost IgHVs that exist in sharks and frogs. We also found evidence of surprisingly low TCRdelta expression and repertoire diversity in this species. PMID- 26809969 TI - Response to "Cross-Species Application of SNP Chips is Not Suitable for Identifying Runs of Homozygosity" by Shafer, Miller, and Kardos. PMID- 26809970 TI - Gender Differences in the Impact of Obesity on Health-Related Quality of Life. AB - This study investigated the association between health-related quality of life (HRQoL) and obesity stratified by sex in 34 935 Korean adults. We used data from the Korea National Health and Nutrition Examination Survey, a cross-sectional, nationwide, population-based survey, from 2007 to 2012. Individuals with higher than average health value scores using the EQ-5D-3L to measure HRQoL were classified as being in good health. Multiple logistic regressions were used to determine the association between obesity and good health. Of the 34 935 adults, 28.0% (9767) were classified as obese, 3.8% (1326) as severely obese, and 23.6% (8249) as overweight. Through multiple logistic regressions after adjustments, women who were severely obese had 31% significantly lower HRQoL than women with normal weight (95% confidence interval = 1.12-1.53). However, the same trend was not found in men. Additional interventional studies would be needed to better understand the causality of the association between obesity and HRQoL in women. PMID- 26809971 TI - Childhood Immunization and Access to Health Care: Evidence From Nepal. AB - This article examines the effect of access to health care center, in terms of travel time, on childhood immunization in Nepal using the 2004 and 2011 waves of the Nepal Living Standards Measurement Surveys. We employ probit and instrumental variable probit estimation methods to estimate the causal effect of travel time on the probability of immunization. Results indicate that travel time to the nearest health center displays a significant negative association with the probability of immunization (coefficient = -0.015,P< .05). Furthermore, the effect of travel time tends to be stronger in rural and distant areas of Nepal's mountain and hill regions. The results suggest that policy interventions should increase the number of mobile clinics in rural villages and provide conditional cash transfer to incentivize immunization coverage at the household level. In addition, household income, parental education, ethnicity, and household location emerge as important determinants of immunization in Nepal. PMID- 26809972 TI - The transparency paradox. Building trust, resolving disputes and optimising logistics on conventional and online drugs markets. AB - BACKGROUND: In recent years, marketplaces in the darknet emerged where vendors and customers can exchange illicit drugs and other goods on digital platforms by using hidden internet services. The main thesis of this paper is that in an online environment, different practices for building trust and reputation emerge that stabilise market processes. METHODS: Qualitative and quantitative data from a recent German project on conventional (offline) small-scale drug dealing as well as qualitative case studies on four online vendors operating on Agora market are used to explore alternative practices for building trust and reputation. They also explore the use of violence and logistics established on cryptomarkets in comparison to traditional dealing. To analyse the data we applied qualitative content analyses. RESULTS: For conventional commercial illicit drug dealing on various kinds of markets, trust between buyer and seller is a crucial issue, often emphasized by restricting deals to well-known persons. While this typically includes face-to-face contact, the opposite is true with online drug trading. It is characteristic of cryptomarkets that the parties involved in a transaction know neither the personal identity nor the physical location of one another. This is realised by using aliases, anonymising software, and cryptocurrencies for payments. Violence typically only plays a role in traditional drug dealing, but mostly, if at all, just as a latent threat for potential rule-breakers. Processing a transaction anonymously includes escrow services for the buyers, which makes trading more reliable, although they cannot completely prevent scamming. Furthermore, online drug marketplaces usually offer a customer feedback system that allows customers to rate vendors and review products. A positive vendor feedback helps building reputation and trust in such an online environment. With regard to logistics, most conventional small-scale dealers restrict their acts of selling to private surroundings to avoid encounters with law enforcement. In cryptomarkets, the purchased drugs are delivered by traditional postal services, sometimes to false addresses or to someone else's name to conceal the identity and address of the buyer. CONCLUSION: On virtual drug markets practices of building trust, conflict resolution and logistics is constantly evolving. They offer improved security solutions on the one hand while on the other hand scamming and fraud seem to be widely used on both online and conventional drug markets. PMID- 26809973 TI - [Cannabis as a therapeutic agent: Focal topic]. PMID- 26809974 TI - [Efficacy, tolerability, and safety of cannabinoids in gastroenterology: A systematic review]. AB - BACKGROUND: The medical use of cannabis is discussed in gastroenterology for inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), and chronic pancreatitis. MATERIALS AND METHODS: A systematic literature search until March 2015 was performed in the databases Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, www.cannabis-med.org , and clinicaltrials.gov. Randomized controlled trials (RCT) investigating herbal cannabis and/or pharmaceutical cannabinoids in IBD, IBS, or chronic pancreatitis with a study duration of >= 4 weeks and a sample size of at least n = 10 per study arm were identified. Clinical outcomes comprised efficacy (pain, nausea, appetite/weight, diarrhea, health-related quality of life, and remission rates for IBD), tolerability (drop-out rate due to side effects), and safety (severe side effects). Methodology quality of RCTs was evaluated with the Cochrane Risk of Bias Tool. RESULTS: Only one RCT treating 21 patients with Crohn's disease and herbal cannabis was identified. The study revealed no significant differences of remission rate because of low statistical power. However, there was a clear tendency for less abdominal pain and improved appetite with medical cannabis. The methodological risk of the study was high. Furthermore, results of two RCTs investigating synthetic cannabis in IBD and chronic pancreatitis, respectively, have not yet been released. No RCT for IBS was found. Several case reports described cannabis-induced acute pancreatitis. CONCLUSIONS: Cannabis may be useful for symptom relief in Crohn's disease such as pain, nausea, and loss of appetite. However, studies with high methodological quality, sufficient sample size, and study duration are mandatory to determine potential therapeutic effects and risks of cannabis in gastroenterology. Currently, use of tetrahydrocannabinol to alleviate symptoms such as pain and appetite loss in Crohn's disease should only be considered in individual patients after failure of established medical therapies and only after careful risk-benefit assessment. PMID- 26809975 TI - [Cannabinoids in palliative care: Systematic review and meta-analysis of efficacy, tolerability and safety]. AB - BACKGROUND: Cannabinoids have multiple medical indications in palliative care, such as relief of pain or nausea or increase of appetite and weight stabilisation. The value of cannabinoids for these indications is not resolved sufficiently for palliative patients. A systematic review with meta-analysis of the efficacy, tolerability and safety on the basis of randomised controlled studies (RCT) or randomised open label or crossover studies has not yet been conducted. MATERIALS AND METHODS: An extensive search for RCTs, randomised open label or crossover studies dealing with the underlying question was performed in the databases of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus and Clinicaltrials.gov up to April 2015. Studies with a duration of >= 2 weeks and >= 10 participants per treatment group were included into analysis. Using a random effects model, pooled estimates of event rates for categorical data and standardized mean differences (SMD) for continuous variables and risk differences (RD) for dichotomous variables were calculated. RESULTS: Out of initially 108 studies 9, with a total of 1561 participants suffering from advanced or end stage diseases, were included. The median study duration of the cancer research was 8 weeks (16 days-11 weeks), of the HIV research 6 weeks (3-12 weeks) and of the study concentrating on Alzheimer's 2 * 6 weeks. The outcome results for cannabis/cannabinoids vs. placebo in patients with cancer were not significant for the 30 % decrease in pain (RD: 0.07; 95 % confidence interval (CI): - 0.01 to 0.16; p = 0.07), caloric intake (SMD: 0.2; 95 % CI: - 0.66 to 1.06; p = 0.65) or sleep problems (SMD: - 0.09; 95 % CI: - 0.62 to 0.43; p = 0.72). In the treatment of HIV cannabinoids were superior to placebo for the outcome of weight change (SMD: 0.57; 95 % CI: 0.22-0.92; p = 0.001). Change in appetite was significant for the treatment of HIV (SMD: 0.57; 95 % CI: 0.11-1.03; p = 0.02), but not for treatment of cancer (SMD: 0.81; 95 % CI: - 1.14 to 2.75; p = 0.42). Nausea/vomiting (SMD: 0.20; 95 % CI: - 0.03 to 0.44; p = 0.09) and health-related quality of life (HRQoL; SMD: 0.00; 95 % CI: - 0.19 to 0.18; p = 0.98) did not show significant differences in the therapy of the two diseases. For the outcomes of tolerability the results were not significant for occurrence of dizziness (RD: 0.03; 95 % CI: - 0.02 to 0.08; p = 0.23) or psychiatric diseases, such as hallucinations or psychosis (RD: - 0.01; 95 % CI: - 0.04 to 0.03; p = 0.69) in the therapy of cancer. The outcome of psychiatric diseases in the treatment of HIV was significant (RD: 0.05; 95 % CI: 0.00-0.11; p = 0.05). The number of withdrawals due to adverse events, as a marker for tolerability, and the reports of serious adverse events as a measure of safety was not significantly different (RD: 1.20; 95 % CI: 0.85-1.71; p = 0.30 and RD: 1.15; 95 % CI: 0.88-1.49; p = 0.30, respectively). Dronabinol vs. megestrol acetate showed a superiority of megestrol in the therapy of cancer associated anorexia for the endpoints change of appetite (49 vs. 75 %; p = 0.0001), weight gain (3 vs. 11 %; p = 0.02), HRQoL (p = 0.003) and tolerability (p = 0.03). There was no difference in the safety of the therapies (p = 0.12). In the treatment of HIV-associated wasting syndrome megestrol acetate was better than dronabinol for the endpoint of weight gain (p = 0.0001), whereas tolerability and safety did not differ. In the therapy of Alzheimer's dronabinol was better than placebo in the endpoint of weight gain according to one study (n = 15). A difference between herbal cannabis and synthetic cannabinoids, analysed by one study (n = 62) could not be found. CONCLUSION: Cannabinoids can lead to an increase in appetite in patients with HIV wasting syndrome but the therapy with megestrol acetate is superior to treatment with cannabinoids. The included studies were not of sufficient duration to answer questions concerning the long term efficacy, tolerability and safety of therapy with cannabis or cannabinoids. Due to the sparse amount of data it is not possible to recommend a favoured use of cannabis or cannabinoids at this point. PMID- 26809976 TI - Trace metals, melanin-based pigmentation and their interaction influence immune parameters in feral pigeons (Columba livia). AB - Understanding the effects of trace metals emitted by anthropogenic activities on wildlife is of great concern in urban ecology; yet, information on how they affect individuals, populations, communities and ecosystems remains scarce. In particular, trace metals may impact survival by altering the immune system response to parasites. Plumage melanin is assumed to influence the effects of trace metals on immunity owing to its ability to bind metal ions in feathers and its synthesis being coded by a pleiotropic gene. We thus hypothesized that trace metal exposure would interact with plumage colouration in shaping immune response. We experimentally investigated the interactive effect between exposure to an environmentally relevant range of zinc and/or lead and melanin-based plumage colouration on components of the immune system in feral pigeons (Columba livia). We found that zinc increased anti-keyhole limpet hemocyanin (KLH) IgY primary response maintenance, buffered the negative effect of lead on anti-KLH IgY secondary response maintenance and tended to increase T-cell mediated phytohaemagglutinin (PHA) skin response. Lead decreased the peak of the anti-KLH IgY secondary response. In addition, pheomelanic pigeons exhibited a higher secondary anti-KLH IgY response than did eumelanic ones. Finally, T-cell mediated PHA skin response decreased with increasing plumage eumelanin level of birds exposed to lead. Neither treatments nor plumage colouration correlated with endoparasite intensity. Overall, our study points out the effects of trace metals on some parameters of birds' immunity, independently from other confounding urbanization factors, and underlines the need to investigate their impacts on other life history traits and their consequences in the ecology and evolution of host-parasite interactions. PMID- 26809977 TI - Vitamin D status in children and adolescents with autoimmune thyroiditis. AB - BACKGROUND: Vitamin D deficiency is a global health problem. Its role as an immune modulator has been recently emphasized. There is increasing evidence for the significant role of vitamin D in reducing the incidence of autoimmune diseases. However, little is known about the status of vitamin D in children and adolescents with autoimmune thyroiditis (AIT). OBJECTIVE: The goal of the present study was to assess vitamin D status in Egyptian children and adolescents with AIT and to explore its relation to biomarkers of autoimmunity and thyroid function. DESIGN: A prevalence case-control study that included 56 children with AIT and 56 healthy, age- and sex-matched subjects that served as the control group. The following was done for all participants: thorough history, physical examination, thyroid ultrasound, measurement of thyroid-stimulating hormone (TSH), free thyroxin (FT4), anti-thyroid peroxidase antibodies (TPOAb), anti thyroglobulin antibody (TgAb) and assessment of serum 25-hydroxy vitamin D (25OHD) level. RESULTS: Overt hypothyroidism was detected in 42/56 while subclinical hypothyroidism was detected in 14/56 of the studied patients. Vitamin D deficiency rate was significantly higher in the AIT group compared to the control subjects (71.4 vs 21.4 %, P < 0.001). In AIT group, the mean level of 25OHD was significantly lower compared to the control group (16.2 +/- 8.2 vs 33.9 +/- 12.7 nmol/L, P < 0.001). The difference was more evident in patients with overt hypothyroidism than those with subclinical hypothyroidism (P < 0.01). There were significant negative correlations between serum 25OHD and age, duration of the disease, BMI, anti-TPOAb, anti-TGAb and TSH (P < 0.001 each). On the other hand, serum 25OHD correlated positively with FT4 levels. While 25OHD level was an independent risk factor for AIT, it failed to qualify as an independent risk for the progression of AIT to overt hypothyroidism after adjustment for other potential confounding factors; age, sex and BMI. CONCLUSIONS: Low serum vitamin D is significantly associated with AIT in Egyptian children. However, vitamin D level is not an independent risk for the progression of AIT to overt hypothyroidism. BMI may have an influence on serum 25OHD levels. PMID- 26809980 TI - Tapia's syndrome: pathogenetic mechanisms, diagnostic management, and proper treatment: a case series. AB - BACKGROUND: Tapia's syndrome is an uncommon disease described in 1904 by Antonio Garcia Tapia, a Spanish otolaryngologist. It is characterized by concomitant paralysis of the hypoglossal (XIIth) and pneumogastric (Xth) nerves. Only 69 cases have been described in the literature. Typically, the reported patients presented with a history of orotracheal intubation. Common symptoms are dysphonia, tongue deviation toward the affected side, lingual motility disturbance, and swallowing difficulty. CASE PRESENTATION: In the report, we describe three cases of Tapia's syndrome in three Caucasian patients who underwent surgery with general anesthesia. Two of these patients underwent neck abscess drainage, and the third had an open reduction of a shoulder fracture. The clinical symptoms of Tapia's syndrome appeared after extubation. All three of our patients recovered their lost function at 3 months after diagnosis. CONCLUSIONS: We underline the importance of performing airway endoscopy and a specific program of swallowing rehabilitation for the proper management of Tapia's syndrome. PMID- 26809978 TI - Wrist circumference as a novel negative risk factor for cardiovascular disease among adult men: a median follow-up of 9 years. AB - PURPOSE: Wrist circumference is an easy to measure anthropometric index of body frame and bone size. The aim of this study was to examine the association of wrist circumference with incidence of cardiovascular disease (CVD) among adult men. METHODS: For this study 2531 male participants aged >=30 years, without any history of CVD were selected and followed from 1999 to 2011. Cox proportional hazard models and logistic regression were used to examine the relation of wrist circumference with incident CVD. RESULTS: A total of 339 cases of CVD were reported throughout a median follow-up of 9.4 years. In the multi-variable Cox model, 1 unit increase of wrist circumference was inversely associated with incident CVD with a HR (95 % CI) of 0.84 (0.72-0.98, P value = 0.02). The receiver operating characteristics curve in a logistic regression model for wrist circumference in prediction of CVD showed a cutoff of 17.75 cm, beyond which was associated with a lower risk for CVD. CONCLUSION: In a population with a high prevalence of CVD risk factors, it was shown that a higher wrist circumference was associated with lower risk for incident CVD. Further studies are needed to explore the underlying mechanisms of this inverse relation. PMID- 26809981 TI - Brucella pinnipedialis in hooded seal (Cystophora cristata) primary epithelial cells. AB - BACKGROUND: Marine Brucella spp. have been isolated from numerous pinniped and cetacean species, but pathological findings in association with infection with Brucella pinnipedialis in pinnipeds have been sparse. The capacity of brucellae to survive and replicate within host macrophages underlies their important ability to produce chronic infections, but previous work has shown that B. pinnipedialis spp. are rapidly eliminated from hooded seal (Cystophora cristata) alveolar macrophages. RESULTS: To investigate if multiplication could take place in other hooded seal cell types, primary epithelial cells were isolated, verified to express the epithelial marker cytokeratin and challenged with three different strains of B. pinnipedialis; B. pinnipedialis sp. nov., B. pinnipedialis hooded seal strain B17, and B. pinnipedialis hooded seal strain 22F1. All strains were steadily eliminated and the amounts of intracellular bacteria were reduced to less than one-third by 48 h post infection. Intracellular presence was verified using immunocytochemistry. CONCLUSIONS: So far, intracellular multiplication in seal cells has not been documented for B. pinnipedialis. The lack of intracellular survival in macrophages, as well as in epithelial cells, together with the fact that pathological changes due to B. pinnipedialis infection is not yet identified in seals, suggests that the bacteria may only cause a mild, acute and transient infection. These findings also contribute to substantiate the hypothesis that seals may not be the primary host of B. pinnipedialis and that the transmission to seals are caused by other species in the marine environment. PMID- 26809982 TI - [Challenges of aging skin: Care and therapy using the example of venous ulcers]. AB - BACKGROUND: One of the most significant, and growing, challenges in modern medicine, i.e. the treatment of chronic wounds, is marked by nonuniform data. This concerns both prevalence and incidence of chronic dermatosis, in particular venous ulcers (ulcus cruris), as well as the impact on the health-related quality of life, and practical and economic parameters of the success of different therapies. PURPOSE: The aim of this work is to examine the epidemiology of chronic wounds, in particular age-associated venous ulcers, their impact on health-related quality of life, the treatment regimen, and practical and economic parameters of the success of different therapies. MATERIALS AND METHODS: Performed were analysis of data on the care of venous ulcers in Germany, based on secondary data of Barmer GEK from 2009 and 2012, comparison with data of a NHS Kent Community Health Trust study, and analysis of studies concerning structures, processes and critical success factors for the treatment of chronic wounds, including economic effects. CONCLUSION: Early causal therapy with treatment based on the stage of the wound, consequent goal-oriented interdisciplinary care, and relapse prophylaxis is critical for successful healing of venous ulcers. The costs of treatment significantly correlate with the duration of treatment which can be reduced by up to 60% using guideline-based concepts for the treatment of chronic wounds. Treatment success, in particular with regard to cost-benefit considerations, can be optimized by telemedicine networks of key players who treat chronic wounds. PMID- 26809984 TI - First-Line Pemetrexed Plus Cisplatin Followed by Gefitinib Maintenance Therapy Versus Gefitinib Monotherapy in East Asian Never-Smoker Patients With Locally Advanced or Metastatic Nonsquamous Non-Small-cell Lung Cancer: Quality of Life Results From a Randomized Phase III Trial. AB - BACKGROUND: The efficacy results from an open-label, randomized, multicenter study found no significant difference in progression-free survival between pemetrexed plus cisplatin followed by maintenance gefitinib (PC/G) and gefitinib monotherapy (G) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) and unknown epidermal growth factor receptor (EGFR) mutation status (hazard ratio favored PC/G). The present report describes the quality of life (QoL) results from that trial. PATIENTS AND METHODS: Chemotherapy-naive, East Asian, light ex-smokers or never-smokers with advanced nonsquamous NSCLC and unknown EGFR mutation status (n = 236) were randomly assigned (1:1) to PC/G or G. EGFR mutation status was subsequently determined for 74 patients. The symptoms and QoL were assessed using the Lung Cancer Symptom Scale (LCSS). The time to worsening of symptoms (TWS) was analyzed using the Kaplan-Meier method. RESULTS: In the overall population, the TWS was generally longer in the G group (n = 109) than in the PC/G group (n = 109) for the LCSS symptoms classified as treatment related (loss of appetite, fatigue) and tumor-related (cough, dyspnea, hemoptysis, pain). In the subgroup of patients with wild-type EGFR, the TWS was generally longer in the PC/G group (n = 13) than in the G group (n = 8) for the tumor-related LCSS symptoms. CONCLUSION: In this study population clinically selected to respond to gefitinib, the LCSS scores were more favorable in the G group than in the PC/G group. Patients with wild-type EGFR tended to show greater improvement in tumor-related LCSS symptoms with chemotherapy than with gefitinib alone. These LCSS outcomes provide further evidence that patients with wild-type EGFR might not benefit from first-line treatment of advanced NSCLC with gefitinib. PMID- 26809986 TI - Patient and disease characteristics associated with late tumour stage at presentation of cervical cancer in northwestern Tanzania. AB - BACKGROUND: About two thirds of patients with cervical cancer in Tanzania present with advanced tumor stage, leading to significant morbidity and mortality. We designed a study to determine the factors associated with the late tumour stage at presentation among patients with cervical cancer in Mwanza. METHODS: This cross-sectional study recruited women at Bugando Medical Centre (BMC) with histologically confirmed cervical cancer from November 2013 to April 2014. Patients were recruited serially until the sample size was reached. RESULTS: A total of 202 women with histologically confirmed cervical cancer were recruited. The mean age of the patients was 50.5 +/- 13.3 years. The majority of patients (n = 129, 63.9%) were diagnosed with late stage disease (IIB-IVB). Patients also presented with severe anemia (n = 78, 38.6%), urinary tract infections (n = 74, 36.6%), hydronephrosis (n = 43, 21.2%), elevated serum creatinine levels (n = 33, 16.3%), vesicovaginal fistula (VVF), (n = 13, 6.4%), lung metastasis (n = 5, 2.4%), metastasis to the urinary bladder (n = 4, 1.9%), rectovaginal fistula (RVF) (n = 3, 1.4%), liver metastasis (n = 2, 0.9%) and hydroureter (n = 2, 0.9%). In multivariate logistic regression, factors associated with late stage at presentation were attending to alternative health practitioners and lack of personal initiative to seek care to formal health facilities (OR 2.3; 95% CI 1.2 4.2, p = 0.011 and OR 2.0; 95 % CI 1.0-3.8, p = 0.028) respectively. CONCLUSION: Communities should be sensitized to women's empowerment, provide community education on early symptoms of cervical cancer, and the importance of early hospital attendance. PMID- 26809987 TI - Extremely low frequency alternating magnetic field-triggered and MRI-traced drug delivery by optimized magnetic zeolitic imidazolate framework-90 nanoparticles. AB - An extremely low frequency alternating magnetic field (ELF-AMF) was demonstrated to be able to effectively trigger drug release from carefully engineered magnetic ZIF-90 nanoparticles. The embedded Fe3O4 nanoparticles or alternatively Gd2O3 nanoparticles serve as effective MRI tracers for potential visualization of drug delivery to ensure drug delivery accuracy. PMID- 26809991 TI - The Carbocation Rearrangement Mechanism, Clarified. AB - The role of protonated cyclopropane (PCP(+)) structures in carbocation rearrangement is a decades-old topic that continues to confound. Here, quantum chemical computations (PBE molecular dynamics, PBE and CCSD optimizations, CCSD(T) energies) are used to resolve the issue. PCP(+) intermediates are neither edge-protonated nor corner-protonated (normally) but possess "closed" structures mesomeric between these two. An updated mechanism for hexyl ion rearrangement is presented and shown to resolve past mysteries from isotope-labeling experiments. A new table of elementary-step barrier heights is provided. The mechanism and barrier heights should be useful in understanding and predicting product distributions in organic reactions, including petroleum modification. PMID- 26809989 TI - Socioeconomic inequalities in stillbirth rates in Europe: measuring the gap using routine data from the Euro-Peristat Project. AB - BACKGROUND: Previous studies have shown that socioeconomic position is inversely associated with stillbirth risk, but the impact on national rates in Europe is not known. We aimed to assess the magnitude of social inequalities in stillbirth rates in European countries using indicators generated from routine monitoring systems. METHODS: Aggregated data on the number of stillbirths and live births for the year 2010 were collected for three socioeconomic indicators (mothers' educational level, mothers' and fathers' occupational group) from 29 European countries participating in the Euro-Peristat project. Educational categories were coded using the International Standard Classification of Education (ISCED) and analysed as: primary/lower secondary, upper secondary and postsecondary. Parents' occupations were grouped using International Standard Classification of Occupations (ISCO-08) major groups and then coded into 4 categories: No occupation or student, Skilled/ unskilled workers, Technicians/clerical/service occupations and Managers/professionals. We calculated risk ratios (RR) for stillbirth by each occupational group as well as the percentage population attributable risks using the most advantaged category as the reference (post secondary education and professional/managerial occupations). RESULTS: Data on stillbirth rates by mothers' education were available in 19 countries and by mothers' and fathers' occupations in 13 countries. In countries with these data, the median RR of stillbirth for women with primary and lower secondary education compared to women with postsecondary education was 1.9 (interquartile range (IQR): 1.5 to 2.4) and 1.4 (IQR: 1.2 to 1.6), respectively. For mothers' occupations, the median RR comparing outcomes among manual workers with managers and professionals was 1.6 (IQR: 1.0-2.1) whereas for fathers' occupations, the median RR was 1.4 (IQR: 1.2-1.8). When applied to the entire set of countries with data about mothers' education, 1606 out of 6337 stillbirths (25 %) would not have occurred if stillbirth rates for all women were the same as for women with post-secondary education in their country. CONCLUSIONS: Data on stillbirths and socioeconomic status from routine systems showed widespread and consistent socioeconomic inequalities in stillbirth rates in Europe. Further research is needed to better understand differences between countries in the magnitude of the socioeconomic gradient. PMID- 26809992 TI - Evaluation of a newly developed piezo actuator-driven pulsed water jet system for liver resection in a surviving swine animal model. AB - BACKGROUND: Preservation of the hepatic vessels while dividing the parenchyma is key to achieving safe liver resection in a timely manner. In this study, we assessed the feasibility of a newly developed, piezo actuator-driven pulsed water jet (ADPJ) for liver resection in a surviving swine model. METHODS: Ten domestic pigs underwent liver resection. Parenchymal transection and vessel skeletonization were performed using the ADPJ (group A, n = 5) or an ultrasonic aspirator (group U, n = 5). The water jet was applied at a frequency of 400 Hz and a driving voltage of 80 V. Physiological saline was supplied at a flow rate of 7 ml/min. After 7 days, the animals were killed and their short-term complications were examined and compared between the two groups. RESULTS: No significant complications, such as massive bleeding, occurred in either group during the surgical procedures. The transection time per transection area was significantly shorter in group A than in group U (1.5 +/- 0.3 vs. 2.3 +/- 0.5 min/cm(2), respectively, P = 0.03). Blood loss per transection area was not significantly different between groups A and U (9.3 +/- 4.2 vs. 11.7 +/- 2.3 ml/cm(2), P = 0.6). All pigs in group A survived for 7 days. No postoperative bleeding or bile leakage was observed in any animal at necropsy. CONCLUSION: The present results suggested that the ADPJ reduces transection time without increasing blood loss. ADPJ is a safe and feasible device for liver parenchymal transection. PMID- 26809994 TI - Spectrophotometric assays for measuring redox biomarkers in blood. AB - The assessment of redox status is most frequently performed by measuring redox biomarkers. The spectrophotometer is the most commonly used analytical instrument in biochemistry. There is a huge number of spectrophotometric redox biomarkers and assays, thus distinguishing the most appropriate biomarkers and protocols is overwhelming. The aim of the present review is to propose valid and reliable spectrophotometric assays for measuring redox biomarkers in blood. It is hoped that this work will help researchers to select the most suitable redox biomarkers and assays. PMID- 26809995 TI - Home Office fights to conceal details of detainee's death. PMID- 26809997 TI - Molecular Mechanism: ERK Signaling, Drug Addiction, and Behavioral Effects. AB - Addiction to psychostimulants has been considered as a chronic psychiatric disorder characterized by craving and compulsive drug seeking and use. Over the past two decades, accumulating evidence has demonstrated that repeated drug exposure causes long-lasting neurochemical and cellular changes that result in enduring neuroadaptation in brain circuitry and underlie compulsive drug consumption and relapse. Through intercellular signaling cascades, drugs of abuse induce remodeling in the rewarding circuitry that contributes to the neuroplasticity of learning and memory associated with addiction. Here, we review the role of the extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase, and its related intracellular signaling pathways in drug-induced neuroadaptive changes that are associated with drug mediated psychomotor activity, rewarding properties and relapse of drug seeking behaviors. We also discuss the neurobiological and behavioral effects of pharmacological and genetic interferences with ERK-associated molecular cascades in response to abused substances. Understanding the dynamic modulation of ERK signaling in response to drugs may provide novel molecular targets for therapeutic strategies to drug addiction. PMID- 26810000 TI - Molecular Mechanisms of Cannabis Signaling in the Brain. AB - Cannabis has been cultivated and used by humans for thousands of years. Research for decades was focused on understanding the mechanisms of an illegal/addictive drug. This led to the discovery of the vast endocannabinoid system. Research has now shifted to understanding fundamental biological questions related to one of the most widespread signaling systems in both the brain and the body. Our understanding of cannabinoid signaling has advanced significantly in the last two decades. In this review, we discuss the state of knowledge on mechanisms of Cannabis signaling in the brain and the modulation of key brain neurotransmitter systems involved in both brain reward/addiction and psychiatric disorders. It is highly probable that various cannabinoids will be found to be efficacious in the treatment of a number of psychiatric disorders. However, while there is clearly much potential, marijuana has not been properly vetted by the medical-scientific evaluation process and there are clearly a range of potentially adverse side effects-including addiction. We are at crossroads for research on endocannabinoid function and therapeutics (including the use of exogenous treatments such as Cannabis). With over 100 cannabinoid constituents, the majority of which have not been studied, there is much Cannabis research yet to be done. With more states legalizing both the medicinal and recreational use of marijuana the rigorous scientific investigation into cannabinoid signaling is imperative. PMID- 26809998 TI - Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings. AB - Herein, we have reviewed the role of glutamate, the major excitatory neurotransmitter in the brain, in a number of neurochemical, -physiological, and behavioral processes mediating the development of alcohol dependence. The findings discussed include results from both preclinical as well as neuroimaging and postmortem clinical studies. Expression levels for a number of glutamate associated genes and/or proteins are modulated by alcohol abuse and dependence. These changes in expression include metabotropic receptors and ionotropic receptor subunits as well as different glutamate transporters. Moreover, these changes in gene expression parallel the pharmacologic manipulation of these same receptors and transporters. Some of these gene expression changes may have predated alcohol abuse and dependence because a number of glutamate-associated polymorphisms are related to a genetic predisposition to develop alcohol dependence. Other glutamate-associated polymorphisms are linked to age at the onset of alcohol-dependence and initial level of response/sensitivity to alcohol. Finally, findings of innate and/or ethanol-induced glutamate-associated gene expression differences/changes observed in a genetic animal model of alcoholism, the P rat, are summarized. Overall, the existing literature indicates that changes in glutamate receptors, transporters, enzymes, and scaffolding proteins are crucial for the development of alcohol dependence and there is a substantial genetic component to these effects. This indicates that continued research into the genetic underpinnings of these glutamate-associated effects will provide important novel molecular targets for treating alcohol abuse and dependence. PMID- 26809999 TI - S-Glutathionylation and Redox Protein Signaling in Drug Addiction. AB - Drug addiction is a chronic relapsing disorder that comes at a high cost to individuals and society. Therefore understanding the mechanisms by which drugs exert their effects is of prime importance. Drugs of abuse increase the production of reactive oxygen and nitrogen species resulting in oxidative stress. This change in redox homeostasis increases the conjugation of glutathione to protein cysteine residues; a process called S-glutathionylation. Although traditionally regarded as a protective mechanism against irreversible protein oxidation, accumulated evidence suggests a more nuanced role for S glutathionylation, namely as a mediator in redox-sensitive protein signaling. The reversible modification of protein thiols leading to alteration in function under different physiologic/pathologic conditions provides a mechanism whereby change in redox status can be translated into a functional response. As such, S glutathionylation represents an understudied means of post-translational protein modification that may be important in the mechanisms underlying drug addiction. This review will discuss the evidence for S-glutathionylation as a redox-sensing mechanism and how this may be involved in the response to drug-induced oxidative stress. The function of S-glutathionylated proteins involved in neurotransmission, dendritic spine structure, and drug-induced behavioral outputs will be reviewed with specific reference to alcohol, cocaine, and heroin. PMID- 26810003 TI - Molecular Changes in Opioid Addiction: The Role of Adenylyl Cyclase and cAMP/PKA System. AB - For centuries, opiate analgesics have had a considerable presence in the treatment of moderate to severe pain. While effective in providing analgesia, opiates are notorious in exerting many undesirable adverse reactions. The receptor targets and the intracellular effectors of opioids have largely been identified. Furthermore, much of the mechanisms underlying the development of tolerance, dependence, and withdrawal have been delineated. Thus, there is a focus on developing novel compounds or strategies in mitigating or avoiding the development of tolerance, dependence, and withdrawal. This review focuses on the adenylyl cyclase and cyclic adenosine 3,5-monophosphate (cAMP)/protein kinase A (AC/cAMP/PKA) system as the central player in mediating the acute and chronic effects of opioids. This chapter also reviews the neuronal adaptive changes in the locus coeruleus, amygdala, periaqueductal gray, and ventral tegmental area induced by acute and chronic actions of opioid because these neuronal adaptive changes in these regions may underlie the behavioral changes observed in opiate users and abusers. PMID- 26810002 TI - Recent Advances in Nicotinic Receptor Signaling in Alcohol Abuse and Alcoholism. AB - Alcohol is the most commonly abused legal substance and alcoholism is a serious public health problem. It is a leading cause of preventable death in the world. The cellular and molecular mechanisms of alcohol reward and addiction are still not well understood. Emerging evidence indicates that unlike other drugs of abuse, such as nicotine, cocaine, or opioids, alcohol targets numerous channel proteins, receptor molecules, and signaling pathways in the brain. Previously, research has identified brain nicotinic acetylcholine receptors (nAChRs), a heterogeneous family of pentameric ligand-gated cation channels expressed in the mammalian brain, as critical molecular targets for alcohol abuse and dependence. Genetic variations encoding nAChR subunits have been shown to increase the vulnerability to develop alcohol dependence. Here, we review recent insights into the rewarding effects of alcohol, as they pertain to different nAChR subtypes, associated signaling molecules, and pathways that contribute to the molecular mechanisms of alcoholism and/or comorbid brain disorders. Understanding these cellular changes and molecular underpinnings may be useful for the advancement of brain nicotinic-cholinergic mechanisms, and will lead to a better translational and therapeutic outcome for alcoholism and/or comorbid conditions. PMID- 26810005 TI - Preface. PMID- 26810001 TI - The Nociceptin Receptor as an Emerging Molecular Target for Cocaine Addiction. AB - Cocaine addiction is a global public health and socioeconomic issue that requires pharmacological and cognitive therapies. Currently there are no FDA-approved medications to treat cocaine addiction. However, in preclinical studies, interventions ranging from herbal medicine to deep-brain stimulation have shown promise for the therapy of cocaine addiction. Recent developments in molecular biology, pharmacology, and medicinal chemistry have enabled scientists to identify novel molecular targets along the pathways involved in drug addiction. In 1994, a receptor that showed a great deal of homology to the traditional opioid receptors was characterized. However, endogenous and exogenous opioids failed to bind to this receptor, which led scientists to name it opioid receptor like receptor, now referred to as the nociceptin receptor. The endogenous ligand of NOPr was identified a year later and named orphanin FQ/nociceptin. Nociceptin and NOPr are widely distributed throughout the CNS and are involved in many physiological responses, such as food intake, nociceptive processing, neurotransmitter release, etc. Furthermore, exogenous nociceptin has been shown to regulate the activity of mesolimbic dopaminergic neurons, glutamate, and opioid systems, and the stress circuit. Importantly, exogenous nociceptin has been shown to reduce the rewarding and addictive actions of a number of drugs of abuse, such as psychostimulants, alcohol, and opioids. This paper reviews the existing literature on the role of endogenous nociceptin in the rewarding and addictive actions of cocaine. The effect of exogenous nociceptin on these processes is also reviewed. Furthermore, the effects of novel small-molecule NOPr ligands on these actions of cocaine are discussed. Overall, a review of the literature suggests that NOPr could be an emerging target for cocaine addiction pharmacotherapy. PMID- 26810007 TI - Hydration-dependent anomalous thermal expansion behaviour in a coordination polymer. AB - A coordination polymer is shown to possess anomalous anisotropic thermal expansion. Guest water molecules present in the as-synthesised material can be removed upon activation without loss of crystal singularity. The fully dehydrated form shows considerably different thermal expansion behaviour as compared to the hydrate. PMID- 26810004 TI - Caenorhabditis elegans as a Model to Study the Molecular and Genetic Mechanisms of Drug Addiction. AB - Drug addiction takes a massive toll on society. Novel animal models are needed to test new treatments and understand the basic mechanisms underlying addiction. Rodent models have identified the neurocircuitry involved in addictive behavior and indicate that rodents possess some of the same neurobiologic mechanisms that mediate addiction in humans. Recent studies indicate that addiction is mechanistically and phylogenetically ancient and many mechanisms that underlie human addiction are also present in invertebrates. The nematode Caenorhabditis elegans has conserved neurobiologic systems with powerful molecular and genetic tools and a rapid rate of development that enables cost-effective translational discovery. Emerging evidence suggests that C. elegans is an excellent model to identify molecular mechanisms that mediate drug-induced behavior and potential targets for medications development for various addictive compounds. C. elegans emit many behaviors that can be easily quantitated including some that involve interactions with the environment. Ethanol (EtOH) is the best-studied drug-of abuse in C. elegans and at least 50 different genes/targets have been identified as mediating EtOH's effects and polymorphisms in some orthologs in humans are associated with alcohol use disorders. C. elegans has also been shown to display dopamine and cholinergic system-dependent attraction to nicotine and demonstrate preference for cues previously associated with nicotine. Cocaine and methamphetamine have been found to produce dopamine-dependent reward-like behaviors in C. elegans. These behavioral tests in combination with genetic/molecular manipulations have led to the identification of dozens of target genes/systems in C. elegans that mediate drug effects. The one target/gene identified as essential for drug-induced behavioral responses across all drugs of abuse was the cat-2 gene coding for tyrosine hydroxylase, which is consistent with the role of dopamine neurotransmission in human addiction. Overall, C. elegans can be used to model aspects of drug addiction and identify systems and molecular mechanisms that mediate drug effects. The findings are surprisingly consistent with analogous findings in higher-level organisms. Further, model refinement is warranted to improve model validity and increase utility for medications development. PMID- 26810008 TI - Diversity in gastroenterology in the United States: Where are we now? Where should we go? PMID- 26810009 TI - Clinical experience of intravenous lacosamide in infants and young children. AB - OBJECTIVE: To review our clinical experience with intravenous (iv) lacosamide (LCM) in children less than 12 years old. BACKGROUND: Use of LCM to treat children with epilepsy has been supported by multiple studies with limited information on iv use in children. DESIGNS/METHODS: All children given iv LCM were identified from 2009 to 2015. Records were audited for demographics, seizure classification, etiology, EEG, imaging, indication. Baseline seizure frequency was based on parental reporting, continuous video EEG and direct observation. RESULTS: 47 patients were identified with median age 6.5 years, 18 less than 3 years old, including 8 younger than 12 months. LCM was an adjunctive therapy of >=2 antiepileptic drugs (AEDs). LCM was administered intravenously to treat epilepsia partialis continua (n = 3, dose range 5-10 mg/kg), status epilepticus (n = 11, median dose 7.2 mg/kg, range 4-11 mg/kg), and acute exacerbation of seizure frequency (n = 18, median dose 4.5 mg/kg, range 1-11 mg/kg). Parenteral form was substituted for oral form for 10 children treated with maintenance LCM unable to ingest/tolerate enteral medication and 5 who were given iv LCM to initiate maintenance treatment (median dose 4 mg/kg, range: 2-10 mg/kg). The infusion was effective for 24 out of 37 children (65%) naive to LCM. Sedation (one with ataxia) was noted in 5/36 children (14%), without any other identified adverse events. CONCLUSION: This is the first published retrospective study of very young critically ill children receiving iv LCM. The acute tolerability at this dosing range represents a positive trend and need confirmation from larger studies. PMID- 26810012 TI - The effect of marriage on stage at diagnosis and survival in women with cervical cancer. AB - PURPOSE: This study assessed the effect of marital status on stage at diagnosis and survival in women with cervical cancer. METHODS: Cervical cancer cases diagnosed between 2000 and 2010 were identified from the Surveillance, Epidemiology and End Results (SEER) program. Patient demographic and clinical characteristics were compared by marital status. Multivariate logistic and Cox proportional hazard regression models were performed to calculate odds ratios of advanced stage at diagnosis and hazard ratios of death risk respectively. RESULTS: Among 31 425 women, 46% of cases were married at the time of diagnosis. Married women were more commonly diagnosed at a localized stage (55%) compared to other non-marital groups (47% of singles, 42% of separated/divorced, and 28% of widowers, p < 0.001). After controlling for age, race/ethnicity, period of diagnosis, histology, and SEER area, single [adjusted odds ratio (aOR) 1.41; 95% Confidence Interval (CI) 1.33-1.49], separated/divorced [aOR 1.44; 95% CI 1.34 1.55], and widowed women [aOR 1.43; 95% CI 1.31-1.58] were all more likely to be diagnosed at an advanced stage compared to married women. In terms of prognosis, single (adjusted hazard ratio (aHR) 1.35; 95% CI 1.28-1.43), separated/divorced (aHR 1.22; 95% CI 1.15-1.29), and widowed women (aHR 1.28; 95% CI 1.19-1.36) had significant increased risk of death compared to married women. Adjusting for insurance status did not change the findings. CONCLUSION: Being married is associated with earlier diagnosis and a more favorable prognosis for cervical cancer among US women. Interventions to improve prognosis for unmarried women, including increasing use of cervical cancer screenings, are warranted. PMID- 26810015 TI - How sensitive is the deltoid moment arm to humeral offset changes with reverse total shoulder arthroplasty? AB - BACKGROUND: Reverse total shoulder arthroplasty commonly treats cuff-deficient or osteoarthritic shoulders not amenable to rotator cuff repair. This study investigates deltoid moment arm sensitivity to variations in the joint center and humeral offset of 3 representative reverse total shoulder arthroplasty subjects. We hypothesized that a superior joint implant placement may exist, indicated by muscle moment arms, compared with the current actual surgical implant configuration. METHODS: Moment arms for the anterior, lateral, and posterior aspects of the deltoid muscle were determined for 1521 perturbations of the humeral offset location away from the surgical placement in a subject-specific musculoskeletal model with motion defined by subject-specific in vivo abduction kinematics. The humeral offset was varied from its surgical position +/-4 mm in the anterior/posterior direction, +/-12 mm in the medial/lateral direction, and 10 to 14 mm in the superior/inferior direction. RESULTS: The anterior deltoid moment arm varied in humeral offset and center of rotation up to 20 mm, primarily in the medial/lateral and superior/inferior directions. The lateral deltoid moment arm varied in humeral offset up to 20 mm, primarily in the medial/lateral and anterior/posterior directions. The posterior deltoid moment arm varied up to 15 mm, primarily in early abduction, and was most sensitive to humeral offset changes in the superior/inferior direction. DISCUSSION: High variations in muscle moment arms were found for all 3 deltoid components, presenting an opportunity to dramatically change the deltoid moment arms through surgical placement of the reverse shoulder components and by varying the overall offset of the humerus. LEVEL OF EVIDENCE: Basic Science Study; Computer Modeling. PMID- 26810014 TI - The prognostic role of preoperative serum C-reactive protein in predicting the biochemical recurrence in patients treated with radical prostatectomy. AB - BACKGROUND: To assess the prognostic value of preoperative C-reactive protein (CRP) serum levels for prognostication of biochemical recurrence (BCR) after radical prostatectomy (RP) in a large multi-institutional cohort. METHODS: Data from 7205 patients treated with RP at five institutions for clinically localized prostate cancer (PCa) were retrospectively analyzed. Preoperative serum levels of CRP within 24 h before surgery were evaluated. A CRP level ?0.5 mg dl(-1) was considered elevated. Associations of elevated CRP with BCR were evaluated using univariable and multivariable Cox proportional hazards regression models. Harrel's C-index was used to assess prognostic accuracy (PA). RESULTS: Patients with higher Gleason score on biopsy and RP, extracapsular extension, seminal vesicle invasion, lymph node metastasis, and positive surgical margins status had a significantly elevated preoperative CRP compared to those without these features. Patients with elevated CRP had a lower 5-year BCR survival proportion as compared to those with normal CRP (55% vs 76%, respectively, P<0.0001). In pre and postoperative multivariable models that adjusted for standard clinical and pathologic features, elevated CRP was independently associated with BCR (P<0.001). However, the addition of preoperative CRP did not improve the accuracy of the standard pre- and postoperative models for prediction of BCR (70.9% vs 71% and 78.9% vs 78.7%, respectively). CONCLUSIONS: Preoperative CRP is elevated in patients with pathological features of aggressive PCa and BCR after RP. While CRP has independent prognostic value, it does not add prognostically or clinically significant information to standard predictors of outcomes. PMID- 26810016 TI - Comparison of proximal humeral bone stresses between stemless, short stem, and standard stem length: a finite element analysis. AB - BACKGROUND: The stem lengths of humeral components used in shoulder arthroplasty vary; however, the literature on these devices is limited. This finite element study investigates the effect of humeral component length on stresses in the proximal humerus. METHODS: Intact and 3 reconstructed (standard length, short, and stemless implants) finite element models were created from shoulder computed tomography scan data (N = 5). Loading was simulated at varying abduction angles (15 degrees , 45 degrees , and 75 degrees ). The average bone stress (represented as a percentage of intact values) was reported at 8 transverse slices. In addition, the overall average change in cortical and trabecular bone stresses was quantified. RESULTS: Cortical bone stresses in the most proximal slice for the standard (58% +/- 12%) and short (78% +/- 10%) stem models were significantly reduced compared with the intact (100%) and stemless (101% +/- 6%) models (P = .005). These reductions persisted in the second cortical slice for the standard stem compared with the intact, stemless, and short models (P = .025). Interestingly, stresses in the trabecular bone within these proximal slices were significantly elevated when stemless implants were used compared with all other implants (P < .001), regardless of abduction angle. CONCLUSION: Reducing stem length produced humeral stresses that more closely matched the intact stress distribution in proximal cortical bone. Opposing trends presented in the proximal trabecular bone, probably because of differences in load transfer when shorter stems are used. Accordingly, the results suggest that implant stem length is 1 variable that can be modified in an attempt to better mimic intact bone stresses during humeral component insertion, provided stem fixation is adequate. PMID- 26810017 TI - Are spinoglenoid ganglion cysts early markers of glenohumeral arthritis? AB - HYPOTHESIS: The objective of this study was to improve our understanding of the pathogenesis and symptoms of ganglion cysts (GCs) in the spinoglenoid notch. Two hypotheses were tested: (1) the labral tears responsible for these cysts are mainly degenerative and nontraumatic, (2) spinoglenoid cysts are early magnetic resonance image (MRI) markers of eccentric posterior glenoid wear. MATERIALS AND METHODS: This was a descriptive diagnostic study. Patients were included when a spinoglenoid cyst was discovered after complaints of pain in the posterosuperior aspect of the shoulder. MRI and arthroscopy were used to classify the glenoid GC and characterize the glenohumeral joint. The GCs were classified into 1 of 3 types: GC0 (isolated cyst), GC1 (cyst and associated labral lesion), and GC2 (cyst and associated labral and cartilage lesion). RESULTS: Twenty patients (average age, 43 years) were included between 2000 and 2014. There were 7 GC0, 8 GC1, and 5 GC2 type cysts. Isolated labral tears (GC1) were always located posteriorly, without anterior extension or glenoid detachment. The humeral subluxation index was above 55% in 75% of shoulders, including all of the type GC2 shoulders. The 5 GC2 shoulders had type B1, B2, or C glenoids. CONCLUSIONS: The management of paraglenoid labral cysts must go beyond addressing the suprascapular nerve compression related to traumatic labral detachment, and surgeons should look automatically for associated degenerative joint damage. The diagnosis of GCs should be supplemented by humeral subluxation index measurement on computed tomography scan or MRI, and the patient should be informed that joint related posterior shoulder pain might persist in cases of GC1 and GC2. LEVEL OF EVIDENCE: Basic Science Study; Anatomy; Imaging and In Vivo. PMID- 26810018 TI - Risk of insufficient internal rotation after bilateral reverse shoulder arthroplasty: clinical and patient-reported outcome in 57 patients. AB - BACKGROUND: Bilateral reverse shoulder arthroplasty (RSA) is controversial because of potential rotational deficits impairing daily living activities. We assessed achievement of insufficient internal rotation (IR) and associated factors in bilateral RSA patients. METHODS: Fifty-seven staged bilateral RSA patients with a minimum of 1 year of follow-up after the second intervention were identified from our local monocentric register. Shoulder range of motion (including IR using the Apley scratch test), strength, and Constant and Shoulder Pain and Disability Index scores were assessed preoperatively and 6, 12, and 24 months postoperatively. RESULTS: Before surgery, both shoulders were similar regarding imaging parameters, but first operated shoulders tended to have poorer function. One year after the first RSA, 21% of patients had insufficient IR (not reaching the lumbosacral junction) compared with 33% after the second intervention (P = .180). At 2 years, 5% of patients had insufficient IR on both sides. Patients with insufficient IR on the second side at baseline (relative risk [RR], 1.8 [1.0-3.2]) and patients with insufficient IR 1 year after the first RSA (RR, 3.0 [1.6-5.6]) were more likely to have insufficient IR 1 year after the second RSA. Constant and Shoulder Pain and Disability Index scores and abduction of the second side were significantly worse 1 year after the second RSA (P <= .047); at 2 years, there were no differences in functional outcome between shoulders. CONCLUSION: A minority of bilateral RSA patients did not achieve sufficient IR on at least 1 side. Staged surgery is justified, particularly when the outcome of the initial operation is satisfactory. PMID- 26810019 TI - Emergency Department Presentations for Injuries in Older Adults Independently Known to be Victims of Elder Abuse. AB - BACKGROUND: Elder abuse is under-recognized by emergency department (ED) providers, largely due to challenges distinguishing between abuse and accidental trauma. OBJECTIVE: To describe patterns and circumstances surrounding elder abuse related and potentially abuse-related injuries in ED patients independently known to be physical elder abuse victims. METHODS: ED utilization of community-dwelling victims of physical elder abuse in New Haven, CT from 1981-1994 was analyzed previously. Cases were identified using Elderly Protective Services data matched to ED records. Sixty-six ED visits were judged to have high probability of being related to elder abuse and 244 were of indeterminate probability. We re-examined these visits to assess whether they occurred due to injury. We identified and analyzed in detail 31 injury-associated ED visits from 26 patients with high probability of being related to elder abuse and 108 visits from 57 patients with intermediate probability and accidental injury. RESULTS: Abuse-related injuries were most common on upper extremities (45% of visits) and lower extremities (32%), with injuries on head or neck noted in 13 visits (42%). Bruising was observed in 39% of visits, most commonly on upper extremities. Forty-two percent of purportedly accidental injuries had suspicious characteristics, with the most common suspicious circumstance being injury occurring more than 1 day prior to presentation, and the most common suspicious injury pattern being maxillofacial injuries. CONCLUSION: Victims of physical elder abuse commonly have injuries on the upper extremities, head, and neck. Suspicious circumstances and injury patterns may be identified and are commonly present when victims of physical elder abuse present with purportedly accidental injuries. PMID- 26810020 TI - Does Right Lower Quadrant Abdominal Ultrasound Accurately Identify Perforation in Pediatric Acute Appendicitis? AB - BACKGROUND: Acute appendicitis is the most common cause of acute abdomen in pediatric emergency department (ED) visits, and right lower quadrant abdominal ultrasound (RLQUS) is a valuable diagnostic tool in the clinical approach. The utility of ultrasound in predicting perforation has not been well-defined. OBJECTIVES: We sought to determine the sensitivity of RLQUS to identify perforation in pediatric patients with appendicitis. METHODS: A chart review of all patients 3 to 21 years of age who received a radiographic work-up and who were ultimately diagnosed with perforated appendicitis between 2010 and 2013 at a pediatric ED was conducted. The final read for ultrasonography was compared to either the operative diagnosis, surgical pathology diagnosis, or further imaging results (if the patient was managed nonoperatively). Test characteristics were calculated for the identification of appendicitis and identification of perforation. RESULTS: Of the 539 patients evaluated for appendicitis, 144 (26.7%) patients had appendicitis, and 40 of these (27.8%) were perforated. Thirty-nine had RLQUS performed as part of their evaluation. Of these, 28 had positive findings for appendicitis, and 9 were read as definite or possible perforated appendicitis. The sensitivity of RLQUS for the diagnosis of appendicitis in the group with perforation was 77.1% (95% confidence interval [CI], 59.4-89%) and the sensitivity for diagnosing a perforation was 23.1% (95% CI, 11.1-39.3%). CONCLUSION: There was a low rate of detection of perforation by RLQUS in our pediatric population. If larger studies confirm this, additional imaging should be recommended in patients with a high suspicion of perforation and in whom a diagnosis of perforation would change management. PMID- 26810021 TI - Dispatch of Helicopter Emergency Medical Services Via Advanced Automatic Collision Notification. AB - BACKGROUND: Advanced automatic collision notification (AACN) is a system for predicting occupant injury from collision information. If the helicopter emergency medical services (HEMS) physician can be alerted by AACN, it may be possible to reduce the time to patient contact. OBJECTIVE: The purpose of this study was to validate the feasibility of early HEMS dispatch via AACN. METHODS: A full-scale validation study was conducted. A car equipped with AACN was made to collide with a wall. Immediately after the collision, the HEMS was alerted directly by the operation center, which received the information from AACN. Elapsed times were recorded and compared with those inferred from the normal, real-world HEMS emergency request process. RESULTS: AACN information was sent to the operation center only 7 s after the collision; the HEMS was dispatched after 3 min. The helicopter landed at the temporary helipad 18 min later. Finally, medical intervention was started 21 min after the collision. Without AACN, it was estimated that the HEMS would be requested 14 min after the collision by fire department personnel. The start of treatment was estimated to be at 32 min, which was 11 min later than that associated with the use of AACN. CONCLUSIONS: The dispatch of the HEMS using the AACN can shorten the start time of treatment for patients in motor vehicle collisions. This study demonstrated that it is feasible to automatically alert and activate the HEMS via AACN. PMID- 26810022 TI - Ultrasonographic Diagnosis of Intrauterine Fetal Decapitation Secondary to Amniotic Band Sequence: A Case Report. AB - BACKGROUND: Amniotic band sequence (ABS) is a rare disorder that can result in a wide spectrum of congenital craniofacial, limb, trunk, and viscera deformities. One of the more rare manifestations of ABS is intrauterine fetal decapitation. CASE REPORT: This case report presents the ultrasonographic diagnosis of first trimester intrauterine fetal demise resulting from decapitation secondary to amniotic band sequence. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case report presents a rare and atypical presentation of intrauterine demise valuable for an emergency physician to recognize while performing or reviewing pelvic ultrasounds. It is important for the clinician to understand and counsel the patient that subsequent pregnancies will not be at increased risk due to a prior miscarriage from ABS, as opposed to other etiologies of first-trimester spontaneous abortion. PMID- 26810023 TI - Pylephlebitis Complicating Acute Appendicitis: Prompt Diagnosis with Contrast Enhanced Computed Tomography. AB - BACKGROUND: Pylephlebitis, a rare complication of abdominal infections, is a septic thrombophlebitis of the portal venous system with high rates of morbidity and mortality. CASE REPORT: We present a case of pylephlebitis complicating acute appendicitis and report the utility of a computed tomography scan in the diagnosis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The prompt diagnosis and appropriate treatment of pylephlebitis are crucial to reduce morbidity and mortality, but clinical presentation is often nonspecific. A computed tomography scan is instrumental in the early diagnosis of pylephlebitis because it readily reveals the thrombus in the mesenteric or portal vein in the setting of acute appendicitis. Early and aggressive treatment with broad-spectrum antibiotics is necessary, and anticoagulation therapy can also be used to prevent bowel ischemia. PMID- 26810024 TI - Man with Rash After Smoke Inhalation. PMID- 26810025 TI - Rapid Detection of Intracardiac Thrombus with Bedside Echocardiography. PMID- 26810026 TI - Seeking mental health information and support online: experiences and perspectives of young people receiving treatment for first-episode psychosis. AB - AIM: Limited knowledge exists on youth mental health service users' experiences and perspectives of seeking mental health information, services and support online. Such information is important for developing online resources that are tailored to the needs of youth with different types of mental health concerns. The purpose of this study was to better understand the experiences and perspectives of young people receiving treatment for first-episode psychosis (FEP) on using web-based and mobile technologies for accessing mental health information, services and support. METHODS: A qualitative approach using focus group methods was used. Seventeen participants between the ages of 21 and 35 were recruited from a specialized early intervention program for psychosis. A thematic analysis was conducted. RESULTS: The results are organized under three related themes: striving towards a better understanding of the illness and treatment; encountering multiple issues with accessing information online; and valuing online mental health information and support. The majority of participants described online activities related to information and support, rather than specific types of mental health services or interventions. CONCLUSIONS: Youth receiving treatment for FEP value accessing mental health information and support online; however, they encounter several challenges in this regard. The findings can inform the development of online resources and strategies that meet the needs of service users. This study also highlights the importance for mental healthcare professionals to address the topic of online mental health information and support seeking within the context of providing services to young people. PMID- 26810027 TI - Impact of a Mobile Phone Intervention to Reduce Sedentary Behavior in a Community Sample of Adults: A Quasi-Experimental Evaluation. AB - BACKGROUND: Greater time spent sedentary is linked with increased risk of breast, colorectal, ovarian, endometrial, and prostate cancers. Given steadily increasing rates of mobile phone ownership, mobile phone interventions may have the potential to broadly influence sedentary behavior across settings. OBJECTIVE: The purpose of this study was to examine the short-term impact of a mobile phone intervention that targeted sedentary time in a diverse community sample. METHODS: Adults participated in a quasi-experimental evaluation of a mobile phone intervention designed to reduce sedentary time through prompts to interrupt periods of sitting. Participants carried mobile phones and wore accelerometers for 7 consecutive days. Intervention participants additionally received mobile phone prompts during self-reported sitting and information about the negative health impact of prolonged sedentariness. The study was conducted from December 2012 to November 2013 in Dallas, Texas. Linear mixed model regression analyses were conducted to evaluate the influence of the intervention on daily accelerometer-determined estimates of sedentary and active time. RESULTS: Participants (N=215) were predominantly female (67.9%, 146/215) and nonwhite (black: 50.7%, 109/215; Latino: 12.1%, 26/215; other: 5.6%, 12/215). Analyses revealed that participants who received the mobile phone intervention had significantly fewer daily minutes of sedentary time (B=-22.09, P=.045) and more daily active minutes (B=23.01, P=.04) than control participants. CONCLUSIONS: A simple mobile phone intervention was associated with engaging in less sedentary time and more physical activity. Findings underscore the potential impact of mobile phone interventions to positively influence sedentary behavior and physical activity. PMID- 26810028 TI - Synthesis and Antimicrobial Screening of Novel Thioglycosides and Acyclonucleoside Analogs Carrying 1,2,3-Triazole and 1,3,4-Oxadiazole Moieties. AB - The solvent-free 1,3-dipolar cycloaddition reaction of dimethylacetylene dicarboxylate (1) with 2-chlorophenyl azide (2) afforded 1,2,3-triazole diester 3 that upon hydrazinolysis, furnished the corresponding bis-acid hydrazide 4. The treatment of compound 4 with carbon disulfide in a refluxing potassium hydroxide solution furnished the desired bis-1,3,4-oxadiazole-2-thione 5 tethered to a 1,2,3-triazole moiety. The respective SOx-glycosides 9-11 were obtained by glycosylation of bis-oxadiazole 5 with 2,3,4,6-tetra-O-acetyl-alpha-d glucopyranosyl bromide (6), 2,3,4,6-tetra-O-acetyl-alpha-d-galactopyranosyl bromide (7), and 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-alpha-d-glucopyranosyl chloride (8) in dry acetone in the presence of Et3N, which acted as a base. However, alkylation of 5 with halogeno-alkanol 12 or 13, chloroglycerol 14, bromoethers 20 or 21, and epichlohydrin 22 in the presence of K2CO3 in DMF yielded the corresponding acyclonucleoside analogs 16-18 and 23-25. The isopropylidenes 19 and acetyl derivatives 26-28 of the products were also prepared. The newly synthesized compounds were characterized by (1)H NMR, (13)C NMR, 2D NMR, and mass spectra. The compounds were screened for their antibacterial and antifungal activities. A number of the tested compounds exhibited significant antimicrobial activity compared to the reference drugs. PMID- 26810029 TI - Sustainable management and supply of natural and recycled aggregates in a medium size integrated plant. AB - The consumption of natural aggregates in civil engineering applications can cause severe environmental impacts on a regional scale, depleting the stock of bulk resources within a territory. Several methods can improve the environmental sustainability of the whole aggregates' supply process, including natural and recycled aggregates' productive chains, for instance promoting the use of recycled aggregates (RA). However, when quarrying and recycling activities are considered as stand-alone processes, also the RA supply chain may not be as sustainable as expected, due to the high environmental loads associated to transportation, if high distances from the production to the use sites are involved. This work gives some insights on the environmental impact assessment of the aggregates' industry in the Italian context, through a comparative assessment of the environmental loads of natural and recycled aggregates' productive chains. An integrated plant for the extraction of virgin aggregates and recycling of construction and demolition waste (C&DW) was analyzed as significant case study, with the aim to identify the influence of sustainable solutions on the overall emissions of the facility. A Life Cycle Assessment (LCA) approach was used, using site-specific data and paying particular attention on transportation-related impacts, land use, avoided landfill and non-renewable resources preservation. From this work it was possible to evaluate the influence of transportation and PV energy use on the overall environmental emissions of natural and recycled aggregates' productive chains. PMID- 26810030 TI - Potential of phosphorus recovery from sewage sludge and manure ash by thermochemical treatment. AB - All life forms require phosphorus (P), which has no substitute in food production. The risk of phosphorus loss from soil and limited P rock reserves has led to the development of recycling P from industrial residues. This study investigates the potential of phosphorus recovery from sewage sludge and manure ash by thermochemical treatment (ASH DEC) in Finland. An ASH DEC plant could receive 46-76 kt/a of sewage sludge ash to produce 51-85 kt/a of a P-rich product with a P2O5 content of 13-18%, while 320-750 kt/a of manure ash could be supplied to produce 350-830 kt/a of a P-rich product with a P content of 4-5%. The P2O5 potential in the total P-rich product from the ASH DEC process using sewage sludge and manure ash is estimated to be 25-47 kt/a, which is significantly more than the P fertilizer demand in Finland's agricultural industries. The energy efficiency of integrated incineration and the ASH DEC process is more dependent on the total solid content and the subsequent need for mechanical dewatering and thermal drying than on the energy required by the ASH DEC process. According to the results of this study, the treated sewage sludge and manure ash using the ASH DEC process represent significant potential phosphorus sources for P fertilizer production. PMID- 26810031 TI - A review of olive mill solid wastes to energy utilization techniques. AB - In recent years, the utilization of olive industry by-products for energy purposes has gained significant research interest and many studies have been conducted focused on the exploitation of olive mill solid waste (OMSW) derived from the discontinuous or continuous processing of olive fruits. In this review study, the primary characteristics of OMSW and the techniques used to define their thermal performance are described. The theoretical background of the main waste-to-energy conversion pathways of solid olive mill wastes, as well as the basic pre-treatment techniques for upgrading solid fuels, are presented. The study aims to present the main findings and major conclusions of previously published works undertaken in the last two decades focused on the characterization of olive mill solid wastes and the utilization of different types of solid olive mill residues for energy purposes. The study also aims to highlight the research challenges in this field. PMID- 26810032 TI - Changes in microbial community during hydrogen and methane production in two stage thermophilic anaerobic co-digestion process from biowaste. AB - In this paper, the microbial community in a two-phase thermophilic anaerobic co digestion process was investigated for its role in hydrogen and methane production, treating waste activated sludge and treating the organic fraction of municipal solid waste. In the acidogenic phase, in which hydrogen is produced, Clostridium sp. clusters represented 76% of total Firmicutes. When feeding the acidogenic effluent into the methanogenic reactors, these acidic conditions negatively influenced methanogenic microorganisms: Methanosaeta sp., (Methanobacteriales, Methanomicrobiales, Methanococcales) decreased by 75%, 50%, 38% and 52%, respectively. At the same time, methanogenic digestion lowered the numbers of Clostridium sp. clusters due to both pH increasing and substrate reduction, and an increase in both Firmicutes genera (non Clostridium) and methanogenic microorganisms, especially Methanosaeta sp. (208%). This was in accordance with the observed decrease in acetic (98%) and butyric (100%) acid contents. To ensure the activity of the acetate-utilizing methanogens (AUM) and the acetogens, high ratios of H2-utilizing methanogens (HUM)/AUM (3.6) were required. PMID- 26810033 TI - Transdermal immunization of P. falciparum surface antigen (MSP-119) via elastic liposomes confers robust immunogenicity. AB - As transdermal immunization results in poor immunogenicity, which is attributed to poor permeability of antigens through the skin, we believed ultradeformable lipid vesicles (elastic liposome) might address the challenges encountered during transdermal immunization. The elastic liposome, versatile carrier, proves better vehicle for transcutaneous delivery of protein, peptide and nucleic acid antigens. Our recently published article (1) is suggestive of improved immunogenicity of carboxyl-terminal 19 kDa fragment of merozoite surface protein 1 (PfMSP-119) of Plasmodium falciparum when administered subcutaneously via elastic liposomes ( Fig. 1 ). PMID- 26810035 TI - Effects of extreme experimental drought and rewetting on CO2 and CH4 exchange in mesocosms of 14 European peatlands with different nitrogen and sulfur deposition. AB - The quantitative impact of intense drought and rewetting on gas exchange in ombrotrophic bogs is still uncertain. In particular, we lack studies investigating multitudes of sites with different soil properties and nitrogen (N) and sulfur (S) deposition under consistent environmental conditions. We explored the timing and magnitude of change in CO2 (Respiration, Gross Primary Production GPP, and Net Exchange - NE) and CH4 fluxes during an initial wet, a prolonged dry (~100 days), and a subsequent wet period (~230 days) at 12 degrees C in 14 Sphagnum peat mesocosms collected in hollows from bogs in the UK, Ireland, Poland, and Slovakia. The relationship of N and S deposition with GPP, respiration, and CH4 exchange was investigated. Nitrogen deposition increased CO2 fluxes and GPP more than respiration, at least up to about 15 kg N ha(-1) yr(-1) . All mesocosms became CO2 sources during drying and most of them when the entire annual period was considered. Response of GPP to drying was faster than that of respiration and contributed more to the change in NE; the effect was persistent and few sites recovered "predry" GPP by the end of the wet phase. Respiration was higher during the dry phase, but did not keep increasing as WT kept falling and peaked within the initial 33 days of drying; the change was larger when differences in humification with depth were small. CH4 fluxes strongly peaked during early drought and water table decline. After rewetting, methanogenesis recovered faster in dense peats, but CH4 fluxes remained low for several months, especially in peats with higher inorganic reduced sulfur content, where sulfate was generated and methanogenesis remained suppressed. Based on a range of European sites, the results support the idea that N and S deposition and intense drought can substantially affect greenhouse gas exchange on the annual scale. PMID- 26810036 TI - Knockdown of Five Genes Encoding Uncharacterized Proteins Inhibits Entamoeba histolytica Phagocytosis of Dead Host Cells. AB - Entamoeba histolytica is the protozoan parasite that causes invasive amebiasis, which is endemic to many developing countries and characterized by dysentery and liver abscesses. The virulence of E. histolytica correlates with the degree of host cell engulfment, or phagocytosis, and E. histolytica phagocytosis alters amebic gene expression in a feed-forward manner that results in an increased phagocytic ability. Here, we used a streamlined RNA interference screen to silence the expression of 15 genes whose expression was upregulated in phagocytic E. histolytica trophozoites to determine whether these genes actually function in the phagocytic process. When five of these genes were silenced, amebic strains with significant decreases in the ability to phagocytose apoptotic host cells were produced. Phagocytosis of live host cells, however, was largely unchanged, and the defects were surprisingly specific for phagocytosis. Two of the five encoded proteins, which we named E. histolytica ILWEQ (EhILWEQ) and E. histolytica BAR (EhBAR), were chosen for localization via SNAP tag labeling and localized to the site of partially formed phagosomes. Therefore, both EhILWEQ and EhBAR appear to contribute to E. histolytica virulence through their function in phagocytosis, and the large proportion (5/15 [33%]) of gene-silenced strains with a reduced ability to phagocytose host cells validates the previously published microarray data set demonstrating feed-forward control of E. histolytica phagocytosis. Finally, although only limited conclusions can be drawn from studies using the virulence-deficient G3 Entamoeba strain, the relative specificity of the defects induced for phagocytosis of apoptotic cells but not healthy cells suggests that cell killing may play a rate-limiting role in the process of Entamoeba histolytica host cell engulfment. PMID- 26810037 TI - Uncovering an Important Role for YopJ in the Inhibition of Caspase-1 in Activated Macrophages and Promoting Yersinia pseudotuberculosis Virulence. AB - Pathogenic Yersinia species utilize a type III secretion system to translocate Yop effectors into infected host cells. Yop effectors inhibit innate immune responses in infected macrophages to promote Yersinia pathogenesis. In turn,Yersinia-infected macrophages respond to translocation of Yops by activating caspase-1, but different mechanisms of caspase-1 activation occur, depending on the bacterial genotype and the state of phagocyte activation. In macrophages activated with lipopolysaccharide (LPS) prior to Yersinia pseudotuberculosis infection, caspase-1 is activated by a rapid inflammasome-dependent mechanism that is inhibited by translocated YopM. The possibility that other effectors cooperate with YopM to inhibit caspase-1 activation in LPS-activated macrophages has not been investigated. Toward this aim, epistasis analysis was carried out in which the phenotype of aY. pseudotuberculosis yopM mutant was compared to that of a yopJ yopM, yopE yopM, yopH yopM, yopT yopM, or ypkA yopM mutant. Activation of caspase-1 was measured by cleavage of the enzyme, release of interleukin-1beta (IL-1beta), and pyroptosis in LPS-activated macrophages infected with wild-type or mutant Y. pseudotuberculosis strains. Results show enhanced activation of caspase-1 after infection with the yopJ yopM mutant relative to infection by any other single or double mutant. Similar results were obtained with the yopJ, yopM, and yopJ yopM mutants ofY ersinia pestis Following intravenous infection of mice, theY. pseudotuberculosis yopJ mutant was as virulent as the wild type, while the yopJ yopM mutant was significantly more attenuated than the yopM mutant. In summary, through epistasis analysis this work uncovered an important role for YopJ in inhibiting caspase-1 in activated macrophages and in promoting Yersinia virulence. PMID- 26810039 TI - Activities of Murine Peripheral Blood Lymphocytes Provide Immune Correlates That Predict Francisella tularensis Vaccine Efficacy. AB - We previously identified potential correlates of vaccine-induced protection against Francisella tularensis using murine splenocytes and further demonstrated that the relative levels of gene expression varied significantly between tissues. In contrast to splenocytes, peripheral blood leukocytes (PBLs) represent a means to bridge vaccine efficacy in animal models to that in humans. Here we take advantage of this easily accessible source of immune cells to investigate cell mediated immune responses against tularemia, whose sporadic incidence makes clinical trials of vaccines difficult. Using PBLs from mice vaccinated with F. tularensis Live Vaccine Strain (LVS) and related attenuated strains, we combined the control of in vitro Francisella replication within macrophages with gene expression analyses. The in vitro functions of PBLs, particularly the control of intramacrophage LVS replication, reflected the hierarchy of in vivo protection conferred by LVS-derived vaccines. Moreover, several genes previously identified by the evaluation of splenocytes were also found to be differentially expressed in immune PBLs. In addition, more extensive screening identified additional potential correlates of protection. Finally, expression of selected genes in mouse PBLs obtained shortly after vaccination, without ex vivo restimulation, was different among vaccine groups, suggesting a potential tool to monitor efficacious vaccine-induced immune responses against F. tularensis. Our studies demonstrate that murine PBLs can be used productively to identify potential correlates of protection against F. tularensis and to expand and refine a comprehensive set of protective correlates. PMID- 26810038 TI - Interleukin-13 Receptor alpha1-Dependent Responses in the Intestine Are Critical to Parasite Clearance. AB - Nematode infection upregulates interleukin-4 (IL-4) and IL-13 and induces STAT6 dependent changes in gut function that promote worm clearance. IL-4 and IL-13 activate the type 2 IL-4 receptor (IL-4R), which contains the IL-13Ralpha1 and IL 4Ralpha chains. We used mice deficient in IL-13Ralpha1 (IL-13Ralpha1(-/-)) to examine the contribution of IL-13 acting at the type 2 IL-4R to immune and functional responses to primary (Hb1) and secondary (Hb2) infections with the gastrointestinal nematode parasite Heligmosomoides bakeri There were differences between strains in the IL-4 and IL-13 expression responses to Hb1 but not Hb2 infection. Following Hb2 infection, deficient mice had impaired worm expulsion and higher worm fecundity despite normal production of Th2-derived cytokines. The upregulation of IL-25 and IL-13Ralpha2 in Hb1- and Hb2-infected wild-type (WT) mice was absent in IL-13Ralpha1(-/-)mice. Goblet cell numbers and resistin-like molecule beta (RELM-beta) expression were attenuated significantly in IL 13Ralpha1(-/-)mice following Hb2 infections. IL-13Ralpha1 contributes to the development of alternatively activated macrophages, but the type 1 IL-4R is also important. Hb1 infection had no effects on smooth muscle function or epithelial permeability in either strain, while the enhanced mucosal permeability and changes in smooth muscle function and morphology observed in response to Hb2 infection in WT mice were absent in IL-13Ralpha1(-/-)mice. Notably, the contribution of claudin-2, which has been linked to IL-13, does not mediate the increased mucosal permeability following Hb2 infection. These results show that activation of IL-13Ralpha1 is critical for key aspects of the immune and functional responses to Hb2 infection that facilitate expulsion. PMID- 26810040 TI - Quantitative trait locus analysis for pod- and kernel-related traits in the cultivated peanut (Arachis hypogaea L.). AB - BACKGROUND: The cultivated peanut (Arachis hypogaea L.) is an important oil and food crop in the world. Pod- and kernel-related traits are direct factors involved in determining the yield of the peanut. However, the genetic basis underlying pod- and kernel-related traits in the peanut remained largely unknown, which hampered the improvement of peanut through marker-assisted selection. To understand the genetic basis underlying pod- and kernel-related traits in the peanut and provide more useful information for marker-assisted breeding, we conducted quantitative trait locus (QTL) analysis for pod length and width and seed length and width by use of two F2:3 populations derived from cultivar Fuchuan Dahuasheng * ICG 6375 (FI population) and cultivar Xuhua 13 * cultivar Zhonghua 6 (XZ population) in this study. RESULTS: Two genetic maps containing 347 and 228 polymorphic markers were constructed for FI and XZ populations respectively. In total, 39 QTLs explaining 1.25-26.11% of the phenotypic variations were detected in two populations. For the FI population, 26 QTLs were detected between the two environments, among which twelve were not mapped before. For the XZ population, thirteen QTLs were detected, among which eight were not reported before. One QTL for pod width was repeatedly mapped between the two populations. CONCLUSION: The QTL analyses for pod length and width and seed length and width were conducted in this study using two mapping populations. Novel QTLs were identified, which included two for pod length, four for pod width, five for seed length and one for seed width in the FI population, and three for pod length, three for pod width and two for seed width in the XZ population. Our results will be helpful for improving pod- and seed-related traits in peanuts through marker-assisted selection. PMID- 26810042 TI - Leptomeningeal Enhancement in a Patient With Progressive Cranial Neuropathies and Lumbosacral Radiculopathies. PMID- 26810041 TI - The road to drink is paved with high intentions: Expectancies, refusal self efficacy, and intentions among heavy drinking college students. AB - The present study examined the effects of drinking intentions (DI) on alcohol expectancies (AE) and drink refusal self-efficacy (DRSE) in regard to alcohol consumption among heavy drinking undergraduates. Research shows that DRSE buffers against drinking (Young, Hasking, Oei, & Loveday, 2007) and interacts with AE to predict alcohol consumption (Oei & Burrow, 2000). Studies further show that DI is predicted by DRSE (Norman, 2011) and AE (Fleming, Thorson, & Atkin, 2004). However, additional research is needed to understand DI's influence on both DRSE and AE among heavy college drinkers. This research included 344 heavy drinking college students (mean age = 23.06 years, SD = 5.61, 74.71% female) from a large southern university who completed study material as part of a larger intervention. Findings showed that DI, DRSE, and AE interacted with respect to heavy drinking such that DRSE was negatively associated with alcohol consumption, particularly among those low in positive AE and high in negative AE. This relationship was stronger among individuals low in DI relative to those high in DI. DI seems to be an important factor influencing heavy drinking among undergraduate students. Present findings further support DI's associations with heavy drinking, regardless of an individual's DRSE or AE. Implications of this research suggest that it may be beneficial for interventions to target specific aspects of AE, including anxious drinking. PMID- 26810043 TI - Toward Future Photovoltaic-Based Agriculture in Sea. AB - To meet the challenges of climate change and water shortages, combining solar energy-based seawater desalination technologies with floating agriculture stations in one innovative hybrid system would be worthy of investigation for dry and sunny regions for seawater desalination and crop production within the same platform. Here, I discuss the feasibility of such a 'floating farm' or 'bluehouse' in the sea, by comparing it with the use of terrestrial greenhouses. I also debate the potential advantages and shortcomings of such a system. PMID- 26810044 TI - Nalmefene for the treatment of alcohol use disorders: recent data and clinical potential. AB - INTRODUCTION: Few pharmacotherapies are available for alcoholism. Numerous studies indicate the involvement of the opioid-endorphin system in mediating the reinforcing effects of alcohol via dopaminergic neurons. The opioid antagonist naltrexone was found to be effective in alcohol treatment, and the European Medicines Agency has now approved the mu-opioid antagonist und partial kappa agonist nalmefene. AREAS COVERED: This article presents background information on the chemistry of nalmefene and pre-clinical and clinical findings. The three relevant Phase III studies, all of which followed a harm-reduction, "as needed" approach and found reduced alcohol consumption with nalmefene 18 (20) mg, are discussed in detail. EXPERT OPINION: The integration of the "as needed" approach into conventional psychosocial alcohol therapies may be challenging but offers the opportunity to reach otherwise not treated patients. Nalmefene is the first medication to be approved specifically in this indication and seems to be most suitable for patients with alcohol misuse or a rather low physical dependence on alcohol who do not require immediate detoxification or inpatient treatment. Although a categorical distinction between patients who want to stop heavy drinking or drinking at all over time may be somewhat hypothetical, nalmefene offers new treatment options to patients with alcohol use disorder. PMID- 26810045 TI - Examining the Evidence for Using Synbiotics to Treat or Prevent Atopic Dermatitis. PMID- 26810047 TI - Pictorial mnemonic-strategy interventions for children with special needs: Illustration of a multiply randomized single-case crossover design. AB - An innovative single-case crossover design containing multiple forms of randomization was implemented with eight participants in seven weekly sessions, during which instruction was given in the use of two different pictorial mnemonic (memory-enhancing) strategies: one designed to improve the children's learning of the dates of various inventions and the other designed to improve the children's acquisition of unfamiliar vocabulary items. A composite randomization statistical test revealed that when compared with the children's own preferred learning methods, the mnemonic-strategy approach produced the predicted facilitation effects. At the same time, it was evident that mnemonic instruction enhanced children's performance to a greater extent on the vocabulary task than on the inventions task. In-depth examination of both individual student performance profiles and the tasks/procedures were conducted, yielding recommendations and challenges for follow-up single-case intervention research on the topic. PMID- 26810046 TI - Predictors of Hypertension in Survivors of the Great East Japan Earthquake, 2011: A Cross-sectional Study. AB - INTRODUCTION: Many survivors of a major disaster die shortly after the event. Hypertension (HT) is one of the most important risk factors for these disaster related diseases. An urgent need exists to establish methods to detect disaster survivors with HT and start medication immediately, as those with no injuries or symptoms may not be examined and medical teams cannot measure all survivors' blood pressure (BP) because they often do not have sufficient time. OBJECTIVE: The goals of this report were: (1) to evaluate the importance of taking antihypertensive drugs continuously for patients with HT during the sub-acute phase after a major earthquake, when patients cannot attend a clinic because of destruction of the local infrastructure; and (2) to establish simple and reliable predictors to detect evacuees with HT, who require clinical examination and treatment at evacuation shelters or in their homes after a major earthquake. METHODS: Medical rounds were performed at evacuation shelters in Iwate Prefecture after the Great East Japan Earthquake. Forty evacuees were enrolled in a cross sectional study. The effect of taking antihypertensive drugs continuously was evaluated and predictors of HT in evacuees were identified using multiple logistic regression analysis. RESULTS: Twenty-eight evacuees were hypertensive (70%), nine of whom were asymptomatic (32%). Most evacuees who had discontinued antihypertensive medication (92%; 11/12) had very high BP, while those who had continued antihypertensive medication (80%; 8/10) were mildly hypertensive. The systolic BP of those who had discontinued antihypertensive drugs was significantly higher than that of those who had continued hypertensive drugs in the whole cohort (n=40), and also in evacuees diagnosed as having HT at evacuation shelters (n=28; P55 years (aOR, 1.10; 95% CI, 1.01-1.21) predicted HT with a sensitivity of 0.96 and specificity of 0.80. CONCLUSIONS: The results of this study suggest that continuity of antihypertensive medication prevents serious HT at evacuation shelters in the first 10 days after a major earthquake. Onsite medical rounds focusing on simple predictors in an early stage after disasters may be an effective means of detecting and treating hypertensive disaster victims before they succumb to a fatal disease. PMID- 26810048 TI - Storage of cell samples for ToF-SIMS experiments-How to maintain sample integrity. AB - In order to obtain comparable and reproducible results from time-of-flight secondary ion mass spectrometry (ToF-SIMS) analysis of biological cells, the influence of sample preparation and storage has to be carefully considered. It has been previously shown that the impact of the chosen preparation routine is crucial. In continuation of this work, the impact of storage needs to be addressed, as besides the fact that degradation will unavoidably take place, the effects of different storage procedures in combination with specific sample preparations remain largely unknown. Therefore, this work examines different wet (buffer, water, and alcohol) and dry (air-dried, freeze-dried, and critical-point dried) storage procedures on human mesenchymal stem cell cultures. All cell samples were analyzed by ToF-SIMS immediately after preparation and after a storage period of 4 weeks. The obtained spectra were compared by principal component analysis with lipid- and amino acid-related signals known from the literature. In all dry storage procedures, notable degradation effects were observed, especially for lipid-, but also for amino acid-signal intensities. This leads to the conclusion that dried samples are to some extent easier to handle, yet the procedure is not the optimal storage solution. Degradation proceeds faster, which is possibly caused by oxidation reactions and cleaving enzymes that might still be active. Just as well, wet stored samples in alcohol struggle with decreased signal intensities from lipids and amino acids after storage. Compared to that, the wet stored samples in a buffered or pure aqueous environment revealed no degradation effects after 4 weeks. However, this storage bears a higher risk of fungi/bacterial contamination, as sterile conditions are typically not maintained. Thus, regular solution change is recommended for optimized storage conditions. Not directly exposing the samples to air, wet storage seems to minimize oxidation effects, and hence, buffer or water storage with regular renewal of the solution is recommended for short storage periods. PMID- 26810049 TI - [Glomerulopathies with organized monoclonal immunoglobulin deposits]. AB - The spectrum of glomerular disorders with organized immunoglobulin (Ig) deposits is heterogeneous. It encompasses 2 mains categories: glomerulopathies with fibrillary deposits are mostly represented by immunoglobulinic amyloidosis (most commonly AL amyloidosis, characterized by monoclonal light chain deposits often of the lambda isotype), and pseudo-amyloid fibrillary glomerulonephritis in which deposits predominantly contain polyclonal IgG4. Glomerulopathies with microtubular deposits include cryoglobulinemic glomerulonephritis (type I and type II, with or without detectable serum cryoglobulin) and glomerulonephritis with organized microtubular monoclonal Ig deposits (GOMMID) also referred to as immunotactoid glomerulopathy. Pathological diagnosis requires meticulous studies by light microscopy (with systematic Congo red staining), immunofluorescence with specific conjugates, and electron microscopy. Ultrastructural studies are required to differentiate amyloid fibrils (8 to 10 nm in external diameter), pseudo-amyloid fibrils (15-20 nm) and microtubules (10 to 50 nm in external diameter, with a central hollow core). Glomerular deposits in type I cryoglobulinemic glomerulonephritis are arranged into parallel straight microtubules similar to those observed in GOMMID, but with different topography that allows distinction between the two entities. Glomerular substructures composed of circulating Igs should be distinguished from collagen fibrils that are commonly observed in glomerular disorders with or without deposition of monoclonal or polyclonal Igs. PMID- 26810050 TI - Facile Synthesis of Reductively Degradable Biopolymers Using Cystamine Diisocyanate as a Coupling Agent. AB - Reductively degradable biopolymers have emerged as a unique class of smart biomedical materials. Here, a functional coupling agent, cystamine diisocyanate (CDI), was designed to offer a facile access to reductively degradable biopolymers via polycondensation with various diols. CDI was readily obtained with a decent yield of 46% by reacting cystamine dihydrochloride with triphosgene. The polycondensation of oligo(ethylene glycol) diol (Mn = 0.4 or 1.5 kg/mol) or oligo(epsilon-caprolactone) diol (Mn = 0.53 kg/mol) with CDI in N,N dimethylformamide at 60 degrees C using dibutyltin dilaurate as a catalyst afforded reductively degradable poly(ethylene glycol) (SSPEG, Mn = 6.2-76.8 kg/mol) or poly(epsilon-caprolactone) (SSPCL, Mn = 6.8-16.3 kg/mol), in which molecular weights were well controlled by diol/CDI molar ratios. Moreover, PEG SSPCL-PEG triblock copolymers could be readily prepared by reacting dihydroxyl terminated SSPCL with PEG-isocyanate derivative. PEG-SSPCL-PEG with an Mn of 5.0 16.3-5.0 kg/mol formed small-sized micelles with an average diameter of about 85 nm in PB buffer. The in vitro release studies using doxorubicin (DOX) as a model drug showed that, in sharp contrast to reduction-insensitive PEG-PCL(HDI)-PEG controls, drug release from PEG-SSPCL-PEG micelles was fast and nearly complete in 24 h under a reductive condition containing 10 mM glutathione. The confocal microscopy experiments in drug-resistant MCF-7 cells (MCF-7/ADR) displayed efficient cytoplasmic DOX release from PEG-SSPCL-PEG micelles. MTT assays revealed that DOX-loaded PEG-SSPCL-PEG micelles were much more potent against MCF 7/ADR cells than reduction-insensitive PEG-PCL(HDI)-PEG controls (IC50: 6.3 vs 55.4 MUg/mL). It should further be noted that blank PEG-SSPCL-PEG micelles were noncytotoxic up to a tested concentration of 1 mg/mL. Hence, cystamine diisocyanate appears to be an innovative coupling agent that facilitates versatile synthesis of biocompatible and reductively degradable biopolymers. PMID- 26810051 TI - Factors affecting dignity of patients with multiple sclerosis. AB - RATIONALE: MS is one of the most common chronic diseases of the nervous system. Apart from disease progression, other complications such as unemployment, separation and divorce could potentially threat patients' dignity. Most of the previous studies have been done of maintaining patients' dignity in interaction with healthcare team, but studies on affecting factors of dignity in chronic patients in the society and in interaction with usual people are scarce. AIM: We aimed to investigate factors affecting dignity of Iranian patients with MS in daily living and in interaction of them with the society. METHODS: In this qualitative study, 13 patients with multiple sclerosis were chosen by purposive sampling and semi-structured interviews were conducted until data saturation. The study was done in Tehran, the capital city of Iran. RESULTS: Factors affecting dignity were classified as 'personal factors' and 'social factors'. Personal factors consist of the following subcategories: patients' communication with self, patients' knowledge, patients' values and beliefs and patients' resources. Social factors include others' communication with patients, social knowledge, social values and beliefs and social resources. CONCLUSION: Multiple personal and social factors interfere in perceived patient dignity. In fact, interaction between personal and social factors can be influential in final perceived dignity. By focusing on whole aspects of the patients' lives, we can identify dignity-promoting or dignity-threatening factors and help patients maintain their dignity by taking appropriate measures for moderating threatening factors and improving dignity enhancing ones. PMID- 26810054 TI - Fertility-Sparing Options in Young Women with Cervical Cancer. AB - OPINION STATEMENT: Cervical cancer (CC) is the fourth most frequent tumor and the fourth most common cause of cancer death among women worldwide. Furthermore, more than 40 % of women with early CC are affected during reproductive age and wish to remain fertile. Thus, many patients demand a more conservative policy for managing these lesions in order to have an uneventful pregnancy in the near future. For this reason, interest in fertility preservation strategies has been increasing, and the number of published studies on this topic has grown significantly. Conization was the first fertility-sparing surgical procedure tested in stage IA1 CC. However, in recent decades, other strategies have been tested, particularly for more advanced tumors. The aim of this review is to analyze the main techniques performed in patients with CC who are eligible for fertility-sparing surgery, with particular attention paid to open questions and controversies. PMID- 26810055 TI - Chemotherapy for Muscle-Invasive Bladder Cancer. AB - OPINION STATEMENT: In the last 25 years, there has been an improved understanding of the pathogenesis of muscle-invasive bladder cancer (BC). Development of new treatment strategies has followed. We have progressed from the awareness of the efficacy of platinum compounds, especially cisplatin, as single agents to the development of effective drug combinations with greater attention in improving safety profiles while impacting on survival. Peri-operative chemotherapy (CHT) is the standard of care for non-metastatic disease. The most evidence in terms of a survival advantage is derived from neoadjuvant chemotherapy (NC) trials, but adjuvant medical treatment should be strongly considered when NC has not been utilized. Patient selection and a multidisciplinary approach are essential. Platinum-based CHT is still the standard of care for both early and advanced disease. A deeper knowledge of the pathogenesis of BC will derive from gene expression profiling (GEP), and this will give us new prognostic and predictive tools to develop more targeted treatments. A high mutational rate has been observed in BC, which can generate neoantigens that initiate cancer immunity. Immunotherapy will become a pivotal treatment for BC, in the very near future. Emerging data are encouraging, and these treatments may well revolutionize the medical approach to this disease while CHT will play a less important role. PMID- 26810057 TI - Oral and endotracheal tubes colonization by periodontal bacteria: a case-control ICU study. AB - Periodontal infection is a possible risk factor for respiratory disorders; however, no studies have assessed the colonization of periodontal pathogens in endotracheal tubes (ET). This case-control study analyzed whether periodontal pathogens are able to colonize ET of dentate and edentulous patients in intensive care units (ICU) and whether oral and ET periodontal pathogen profiles have any correlation between these patients. We selected 18 dentate and 18 edentulous patients from 78 eligible ICU patients. Oral clinical examination including probing depth, clinical attachment level, gingival index , and plaque index was performed by a single examiner, followed by oral and ET sampling and processing by quantitative polymerase chain reaction (total bacterial load, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythia). Data were statistically analyzed by Mann-Whitney U, two-way analysis of variance (p < 0.05). Among dentate, there was no correlation between clinical parameters and ET bacterial levels. Both dentate and edentulous patients showed similar ET bacterial levels. Dentate patients showed no correlation between oral and ET bacterial levels, while edentulous patients showed positive correlations between oral and ET levels of A. actinomycetemcomitans, P. gingivalis, and T. forsythia. Periodontal pathogens can colonize ET and the oral cavity of ICU patients. Periodontal pathogen profiles tend to be similar between dentate and edentulous ICU patients. In ICU patients, oral cavity represents a source of ET contamination. Although accompanied by higher oral bacterial levels, teeth do not seem to influence ET bacterial profiles. PMID- 26810059 TI - A survey to identify barriers of implementing an antibiotic checklist. AB - A checklist is an effective implementation tool, but addressing barriers that might impact on the effectiveness of its use is crucial. In this paper, we explore barriers to the uptake of an antibiotic checklist that aims to improve antibiotic use in daily hospital care. We performed an online questionnaire survey among medical specialists and residents with various professional backgrounds from nine Dutch hospitals. The questionnaire consisted of 23 statements on anticipated barriers hindering the uptake of the checklist. Furthermore, it gave the possibility to add comments. We included 219 completed questionnaires (122 medical specialists and 97 residents) in our descriptive analysis. The top six anticipated barriers included: (1) lack of expectation of improvement of antibiotic use, (2) lack of expected patients' satisfaction by checklist use, (3) lack of feasibility of the checklist, (4) negative previous experiences with other checklists, (5) the complexity of the antibiotic checklist and (6) lack of nurses' expectation of checklist use. Remarkably, 553 comments were made, mostly (436) about the content of the checklist. These insights can be used to improve the specific content of the checklist and to develop an implementation strategy that addresses the identified barriers. PMID- 26810058 TI - Improved detection of deeply invasive candidiasis with DNA aptamers specific binding to (1->3)-beta-D-glucans from Candida albicans. AB - Deeply invasive or disseminated candidiasis is a serious and often fatal complication that can occur frequently in immuno-compromised individuals. However, conventional diagnostic methods of Candida albicans display low sensitivity and lack of specificity; the development of rapid and accurate detection methods remains a high priority. Aptamers are single-strand DNA or RNA oligonucleotides that specifically bind to target molecules with high affinity. In this study, we sought to screen high-affinity DNA aptamers that specifically bound to (1->3)-beta-D-glucans from cell wall of Candida albicans using a systematic evolution of ligands by exponential enrichment (SELEX) technique, and further evaluate the diagnostic potential for invasive or disseminated candidiasis with selected aptamers. (1->3)-beta-D-glucans was purified from Candida albicans, and two single DNA aptamers (designated as AU1 and AD1) were selected. Analysis of dissociation constants and binding domains further revealed that these two selected single DNA aptamers (AU1 and AD1) showed high binding affinity (AD1: Kd = 79.76 nM, AD1: Kd = 103.7 nM) and did not bind to the same domain of (1->3)-beta-D-glucans. Next, we further detected (1->3)-beta-D-glucans in serum samples from different groups of patients with Candida albicans infection or simple bacterial infection by using a double-aptamer sandwich enzyme linked oligonucleotide assay (ELONA). The results showed that the sensitivity and specificity of this aptamer-based sandwich ELONA were 92.31 % and 91.94 % respectively. Thus, our study suggests that AU1 and AD1 have potential application for the differentiate diagnosis of deeply invasive candidiasis and provide valuable clues for designing diagnostic agents for the identification of invasive fungal infection. PMID- 26810061 TI - Bacterial vaginosis, aerobic vaginitis, vaginal inflammation and major Pap smear abnormalities. AB - The purpose of this investigation was to evaluate the impact of the vaginal milieu on the presence of abnormal Pap smears and a positive human papilloma virus (HPV) test. A cross-sectional study was conducted between June 2014 and May 2015, evaluating the vaginal discharge by fresh wet mount microscopy and comparing these data with Pap smear findings. Wet mount slides were scored for bacterial vaginosis (BV), aerobic vaginitis (AV), presence of Candida and Trichomonas vaginalis. Cytologic evaluation was done on all Pap smears according to the Bethesda criteria. The cobas(c) HPV Test (Roche) was performed for HPV detection. A total of 622 cases were evaluated. The mean age of the patients was 41.6 +/- 10.65 years (range 21-75). Eighty-three women (13.3 %) had a cytology result worse than low-grade squamous intraepithelial lesion (LSIL). When comparing this group with the one with normal or minor [atypical squamous cells of undetermined significance (ASC-US) or LSIL] Pap smear abnormalities, there were no differences in the presence of Candida (32.5 % vs. 33.2 %, p = 1.0), absence of lactobacilli (38.6 % vs. 32.5 %, p = 0.32) or BV (20.5 % vs. 13.2 %, p = 0.09). On the other hand, moderate or severe inflammation (msI) (41.0 % vs. 28.8 %, p = 0,04), moderate or severe AV (msAV) (16.9 % vs. 7.2 %, p = 0.009) and msAV/BV (37.3 % vs. 20.0 %, p = 0.001) were more common in women with such major cervical abnormalities. No significant association was found between deviations of the vaginal milieu and high-risk HPV infection. The presence of msI or msAV, but not BV, is independently associated with an increased risk of major cervical cytological abnormalities, but not with HPV infection. PMID- 26810062 TI - Safety and efficacy of arthroscopy in the setting of shoulder arthroplasty. AB - Shoulder arthroplasty has become a reliable and reproducible method of treating a range of shoulder pathologies including fractures, osteoarthritis, and rotator cuff arthropathy. Although most patients experience favorable outcomes from shoulder arthroplasty, some patients suffer from persistent symptoms post arthroplasty and it is these patients who present a unique diagnostic and therapeutic challenge. The role of arthroscopy in assessing and treating patients with symptomatic prosthetic joints elsewhere in the body has been established in recent literature. However, the range of pathology that can affect a prosthetic shoulder is distinct from the knee or the hip and requires careful and considered assessment if an accurate diagnosis is to be made. When used alongside other investigations in a comprehensive assessment protocol, arthroscopy can play an important role in the diagnosis and treatment of the problematic shoulder arthroplasty. PMID- 26810060 TI - Manipulation of BCG vaccine: a double-edged sword. AB - Mycobacterium bovis Bacillus Calmette-Guerin (BCG), an attenuated vaccine derived from M. bovis, is the only licensed vaccine against tuberculosis (TB). Despite its protection against TB in children, the protective efficacy in pulmonary TB is variable in adolescents and adults. In spite of the current knowledge of molecular biology, immunology and cell biology, infectious diseases such as TB and HIV/AIDS are still challenges for the scientific community. Genetic manipulation facilitates the construction of recombinant BCG (rBCG) vaccine that can be used as a highly immunogenic vaccine against TB with an improved safety profile, but, still, the manipulation of BCG vaccine to improve efficacy should be carefully considered, as it can bring in both favourable and unfavourable effects. The purpose of this review is not to comprehensively review the interaction between microorganisms and host cells in order to use rBCG expressing M. tuberculosis (Mtb) immunodominant antigens that are available in the public domain, but, rather, to also discuss the limitations of rBCG vaccine, expressing heterologous antigens, during manipulation that pave the way for a promising new vaccine approach. PMID- 26810063 TI - Revision for taper corrosion at the neck-body junction following total hip arthroplasty: pearls and pitfalls. AB - The management of the patient with a recalled, modular neck-body total hip arthroplasty can be complex, as it involves a combination of clinical, technical, and medicolegal challenges. Management begins with a thorough history and physical exam, radiographic evaluation, infection workup, and serum metal ion levels. Three-dimensional imaging is obtained based on patient symptomatology and metal ion levels and is used to evaluate for the presence of an adverse local tissue response as well as the integrity of the existing soft tissue envelope. The decision to perform revision surgery is based on a combination of patient symptomatology, laboratory values, and imaging findings. Revision surgery involves the entire armamentarium of femoral revision techniques, and the acetabulum may need to be revised at the surgeon's discretion. The femoral implant can often be removed without disrupting the femoral bone envelope; however, the surgeon should have a low threshold to perform an extended trochanteric osteotomy. PMID- 26810064 TI - Hormonal control of sulfate uptake and assimilation. AB - Plant hormones have a plethora of functions in control of plant development, stress response, and primary metabolism, including nutrient homeostasis. In the plant nutrition, the interplay of hormones with responses to nitrate and phosphate deficiency is well described, but relatively little is known about the interaction between phytohormones and regulation of sulfur metabolism. As for other nutrients, sulfate deficiency results in modulation of root architecture, where hormones are expected to play an important role. Accordingly, sulfate deficiency induces genes involved in metabolism of tryptophane and auxin. Also jasmonate biosynthesis is induced, pointing to the need of increase the defense capabilities of the plants when sulfur is limiting. However, hormones affect also sulfate uptake and assimilation. The pathway is coordinately induced by jasmonate and the key enzyme, adenosine 5'-phosphosulfate reductase, is additionally regulated by ethylene, abscisic acid, nitric oxid, and other phytohormones. Perhaps the most intriguing link between hormones and sulfate assimilation is the fact that the main regulator of the response to sulfate starvation, SULFATE LIMITATION1 (SLIM1) belongs to the family of ethylene related transcription factors. We will review the current knowledge of interplay between phytohormones and control of sulfur metabolism and discuss the main open questions. PMID- 26810065 TI - The far-upstream element-binding protein 2 is correlated with proliferation and doxorubicin resistance in human breast cancer cell lines. AB - Far-upstream element (FUSE)-binding protein 2 (FBP2) was a member of single stranded DNA-binding protein family; it played an important role in regulating transcription and post-transcription and is involved in the regulation of C-MYC gene expression in liver tumors. However, the role of FBP2 in breast cancer and its mechanism has not been studied yet. Here, we discovered that FBP2 was up regulated in breast cancer tissues and breast cancer cell lines. Moreover, immunohistochemistry analysis demonstrated that up-regulated FBP2 was highly associated with tumor grade, Ki-67, and poor prognosis, which was an independent prognostic factor for survival of breast cancer patients. At the cellular level, we found that FBP2 was correlated with cell cycle progression by accelerating G1/S transition, and knockdown of FBP2 could weaken cell proliferation, anchorage independent cell growth, while enhancing the sensitivity of breast cancer cells to doxorubicin. More importantly, we found that activation of PI3K/AKT pathway could phosphorylate FBP2, and then make FBP2 shuttle from cytoplasm into the nucleus, which was the main mechanism of breast cancer cell proliferation and drug resistance. Taken together, our findings supported the notion that FBP2 might via PI3K/AKT pathway influence breast cancer progression and drug resistance, which might provide a new target for the design of anti-cancer drugs for breast cancer patients. PMID- 26810066 TI - Prognostic impact and potential interaction of EGFR and c-Met in the progression of esophageal squamous cell carcinoma. AB - This study is to examine EGFR and c-Met variation in precancerous lesion, early esophageal squamous cell carcinoma (ESCC), and advanced ESCC and to explore their prognostic significance. EGFR and c-Met were detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Of 158 endoscopy resection (ER) specimens, c-Met high expression and FISH positive were 44.9 and 12.6 %, respectively. EGFR high expression and FISH positive were 2.5 and 19.6 %, respectively. Of 84 surgical specimens, c-Met high expression and FISH positive were 50 and 8.3 %, respectively. EGFR high expression and FISH positive were 7.1 and 28.5 %, respectively. A significant correlation was observed between c-Met and EGFR FISH positive both in ER (P < 0.001) and surgical specimens (P = 0.029). Patients with EGFR high expression had poorer disease-free survival (DFS) and overall survival (OS) (P = 0.031 and P = 0.013) in c-Met high-expression group but not in c-Met low-expression group (P = 0.301 and P = 0.439). C-Met FISH positive did not represent a statistically significant adverse prognosis until 24 months later (P = 0.027 and 0.048). EGFR and c-Met might be involved in the tumorigenesis and development of ESCC. EGFR high expression has different prognostic significance in patients with differing c-Met expression status. C-Met FISH positive represent delayed prognostic factor. PMID- 26810067 TI - DACH1 inhibits the proliferation and invasion of lung adenocarcinoma through the downregulation of peroxiredoxin 3. AB - In this study, we found the expression of Dachshund 1 (DACH1) is downregulated while peroxiredoxin 3 (PRX3) upregulated in both lung adenocarcinoma tissues and cells. Transfection of DACH1 can significantly downregulate PRX3 expression in targeting lung adenocarcinoma cells. Further experimental results demonstrated the evidence that overexpression of DACH1 resulted in significant retardation of in vitro proliferation and invasion of lung adenocarcinoma cells. Direct upregulation of PRX3 by co-transfection of PRX3 messenger RNA (mRNA) can prevent the above alteration caused by DACH1 transfection. Besides, lower DACH1 expression significantly correlated with tumor diameter and tumor invasion in all the 36 patients diagnosed with lung adenocarcinoma in our hospital during the past months. In conclusion, DACH1 can inhibit the proliferation and invasion of lung adenocarcinoma through the downregulation of PRX3. Decreased expression of DACH1 is involved in the initiation and development of lung cancer, which might be an adverse prognostic factor of lung adenocarcinoma. PMID- 26810068 TI - GRIM-19 inhibition induced autophagy through activation of ERK and HIF-1alpha not STAT3 in Hela cells. AB - Gene associated with retinoid-interferon-induced mortality (GRIM-19), an important subunit of mitochondrial complex I, has been identified as a tumor suppressor, and its reduced expression has been reported to be associated with tumorigenesis and metastasis. Autophagy has been proposed as a protective mechanism for cell survival under various stresses, including chemotherapy. However, it remains unknown whether GRIM-19 is linked to autophagy and chemotherapy resistance. Here, we showed that suppression of GRIM-19 by shRNA enhanced cell-type-dependent autophagy by activating extracellular regulated protein kinase (ERK) and hypoxia inducible factor-1a (HIF-1a) in a reactive oxygen species (ROS)-mediated manner, and thereby conferred resistance to paclitaxel. Besides, the antioxidant N-acetyl-L-cysteine (NAC) and autophagy inhibitor 3-MA could in part overcome this resistance. We also found that GRIM-19 expression was significantly correlated with clinical stage and grade in patients with cervical cancers. Taken together, our results indicated that GRIM-19 inhibition induced autophagy and chemotherapy resistance, which could affect prognosis of cervical cancers. Our study has identified new function of GRIM-19 and its underlying mechanism, and it will provide possible avenues for therapeutic targeting in cervical cancers. PMID- 26810069 TI - High TXNDC5 expression predicts poor prognosis in renal cell carcinoma. AB - Clear cell renal cell carcinoma (ccRCC) is the most common primary kidney cancer in adults, and the identification of biomarkers involved in the pathogenesis and prognosis of ccRCC is crucial for early diagnosis and anticancer treatment. In this study, we demonstrate that thioredoxin domain-containing protein 5 (TXNDC5) expression is markedly upregulated in ccRCC tissues in comparison with adjacent non-cancerous tissues through quantitative RT-PCR, Western blotting, and immunohistochemical analyses. Importantly, TXNDC5 expression is negatively correlated with the overall survival of patients. Knockdown of TXNDC5 by siRNAs inhibits the cell growth, migration, and invasion of ccRCC cells as well as sensitizes ccRCC cells to chemotherapeutic drugs, such as Camptothecin and 5 Fluorouracil. Moreover, we used complementary DNA (cDNA) microarray analyses to explore the underlying molecular mechanisms of TXNDC5 in the pathogenesis of ccRCC. We demonstrate that knockdown of TXNDC5 affects the messenger RNA (mRNA) and protein levels of numerous important genes associated with tumorigenesis. In summary, our findings indicate that TXNDC5 performs an essential function in ccRCC pathogenesis and can serve as a novel prognostic marker of ccRCC. PMID- 26810070 TI - Genetic alterations in uncommon low-grade neuroepithelial tumors: BRAF, FGFR1, and MYB mutations occur at high frequency and align with morphology. AB - Low-grade neuroepithelial tumors (LGNTs) are diverse CNS tumors presenting in children and young adults, often with a history of epilepsy. While the genetic profiles of common LGNTs, such as the pilocytic astrocytoma and 'adult-type' diffuse gliomas, are largely established, those of uncommon LGNTs remain to be defined. In this study, we have used massively parallel sequencing and various targeted molecular genetic approaches to study alterations in 91 LGNTs, mostly from children but including young adult patients. These tumors comprise dysembryoplastic neuroepithelial tumors (DNETs; n = 22), diffuse oligodendroglial tumors (d-OTs; n = 20), diffuse astrocytomas (DAs; n = 17), angiocentric gliomas (n = 15), and gangliogliomas (n = 17). Most LGNTs (84 %) analyzed by whole-genome sequencing (WGS) were characterized by a single driver genetic alteration. Alterations of FGFR1 occurred frequently in LGNTs composed of oligodendrocyte like cells, being present in 82 % of DNETs and 40 % of d-OTs. In contrast, a MYB QKI fusion characterized almost all angiocentric gliomas (87 %), and MYB fusion genes were the most common genetic alteration in DAs (41 %). A BRAF:p.V600E mutation was present in 35 % of gangliogliomas and 18 % of DAs. Pathogenic alterations in FGFR1/2/3, BRAF, or MYB/MYBL1 occurred in 78 % of the series. Adult-type d-OTs with an IDH1/2 mutation occurred in four adolescents, the youngest aged 15 years at biopsy. Despite a detailed analysis, novel genetic alterations were limited to two fusion genes, EWSR1-PATZ1 and SLMAP-NTRK2, both in gangliogliomas. Alterations in BRAF, FGFR1, or MYB account for most pathogenic alterations in LGNTs, including pilocytic astrocytomas, and alignment of these genetic alterations and cytologic features across LGNTs has diagnostic implications. Additionally, therapeutic options based upon targeting the effects of these alterations are already in clinical trials. PMID- 26810071 TI - Updated TDP-43 in Alzheimer's disease staging scheme. AB - In this study, we update the TDP-43 in Alzheimer's disease staging scheme by assessing the topography of TDP-43 in 193 cases of Alzheimer's disease, in 14 different brain regions (eight previously described plus six newly reported) and use conditional probability to model the spread of TDP-43 across the 14 brain regions. We show that in addition to the eight original regions we previously reported [amygdala, entorhinal cortex, subiculum, dentate gyrus of the hippocampus, occipitotemporal cortex, inferior temporal cortex, middle frontal cortex and basal ganglia (putamen/globus pallidum)] that TDP-43 is also deposited in the insular cortex, ventral striatum, basal forebrain, substantia nigra, midbrain tectum, and the inferior olive of the medulla oblongata, in Alzheimer's disease. The conditional probability analysis produced six significantly different stages (P < 0.01), and suggests that TDP-43 deposition begins in the amygdala (stage 1), then moves to entorhinal cortex and subiculum (stage 2); to the dentate gyrus of the hippocampus and occipitotemporal cortex (stage 3); insular cortex, ventral striatum, basal forebrain and inferior temporal cortex (stage 4); substantia nigra, inferior olive and midbrain tectum (stage 5); and finally to basal ganglia and middle frontal cortex (stage 6). This updated staging scheme is superior to our previous staging scheme, classifying 100% of the cases (versus 94% in the old scheme), based on criteria provided, and shows clinical significance with some regions and with increasing stage. We discuss the relevance of the updated staging scheme, as well as its impact on the prion-like hypothesis of protein spread in neurodegenerative disease. We also address the issue of whether frontotemporal lobar degeneration with TDP-43 could be the primary pathology in stage 6. PMID- 26810073 TI - Thiol-Based Peroxidases and Ascorbate Peroxidases: Why Plants Rely on Multiple Peroxidase Systems in the Photosynthesizing Chloroplast? AB - Photosynthesis is a highly robust process allowing for rapid adjustment to changing environmental conditions. The efficient acclimation depends on balanced redox metabolism and control of reactive oxygen species release which triggers signaling cascades and potentially detrimental oxidation reactions. Thiol peroxidases of the peroxiredoxin and glutathione peroxidase type, and ascorbate peroxidases are the main peroxide detoxifying enzymes of the chloroplast. They use different electron donors and are linked to distinct redox networks. In addition, the peroxiredoxins serve functions in redox regulation and retrograde signaling. The complexity of plastid peroxidases is discussed in context of suborganellar localization, substrate preference, metabolic coupling, protein abundance, activity regulation, interactions, signaling functions, and the conditional requirement for high antioxidant capacity. Thus the review provides an opinion on the advantage of linking detoxification of peroxides to different enzymatic systems and implementing mechanisms for their inactivation to enforce signal propagation within and from the chloroplast. PMID- 26810072 TI - Reciprocal Control of the Circadian Clock and Cellular Redox State - a Critical Appraisal. AB - Redox signalling comprises the biology of molecular signal transduction mediated by reactive oxygen (or nitrogen) species. By specific and reversible oxidation of redox-sensitive cysteines, many biological processes sense and respond to signals from the intracellular redox environment. Redox signals are therefore important regulators of cellular homeostasis. Recently, it has become apparent that the cellular redox state oscillates in vivo and in vitro, with a period of about one day (circadian). Circadian time-keeping allows cells and organisms to adapt their biology to resonate with the 24-hour cycle of day/night. The importance of this innate biological time-keeping is illustrated by the association of clock disruption with the early onset of several diseases (e.g. type II diabetes, stroke and several forms of cancer). Circadian regulation of cellular redox balance suggests potentially two distinct roles for redox signalling in relation to the cellular clock: one where it is regulated by the clock, and one where it regulates the clock. Here, we introduce the concepts of redox signalling and cellular timekeeping, and then critically appraise the evidence for the reciprocal regulation between cellular redox state and the circadian clock. We conclude there is a substantial body of evidence supporting circadian regulation of cellular redox state, but that it would be premature to conclude that the converse is also true. We therefore propose some approaches that might yield more insight into redox control of cellular timekeeping. PMID- 26810074 TI - Utilizing Natural and Engineered Peroxiredoxins As Intracellular Peroxide Reporters. AB - It is increasingly apparent that nature evolved peroxiredoxins not only as H2O2 scavengers but also as highly sensitive H2O2 sensors and signal transducers. Here we ask whether the H2O2 sensing role of Prx can be exploited to develop probes that allow to monitor intracellular H2O2 levels with unprecedented sensitivity. Indeed, simple gel shift assays visualizing the oxidation of endogenous 2-Cys peroxiredoxins have already been used to detect subtle changes in intracellular H2O2 concentration. The challenge however is to create a genetically encoded probe that offers real-time measurements of H2O2 levels in intact cells via the Prx oxidation state. We discuss potential design strategies for Prx-based probes based on either the redox-sensitive fluorophore roGFP or the conformation sensitive fluorophore cpYFP. Furthermore, we outline the structural and chemical complexities which need to be addressed when using Prx as a sensing moiety for H2O2 probes. We suggest experimental strategies to investigate the influence of these complexities on probe behavior. In doing so, we hope to stimulate the development of Prx-based probes which may spearhead the further study of cellular H2O2 homeostasis and Prx signaling. PMID- 26810075 TI - Distribution and Features of the Six Classes of Peroxiredoxins. AB - Peroxiredoxins are cysteine-dependent peroxide reductases that group into 6 different, structurally discernable classes. In 2011, our research team reported the application of a bioinformatic approach called active site profiling to extract active site-proximal sequence segments from the 29 distinct, structurally characterized peroxiredoxins available at the time. These extracted sequences were then used to create unique profiles for the six groups which were subsequently used to search GenBank(nr), allowing identification of ~3500 peroxiredoxin sequences and their respective subgroups. Summarized in this minireview are the features and phylogenetic distributions of each of these peroxiredoxin subgroups; an example is also provided illustrating the use of the web accessible, searchable database known as PREX to identify subfamily-specific peroxiredoxin sequences for the organism Vitis vinifera (grape). PMID- 26810076 TI - Peroxiredoxins and the Regulation of Cell Death. AB - Cell death pathways such as apoptosis can be activated in response to oxidative stress, enabling the disposal of damaged cells. In contrast, controlled intracellular redox events are proposed to be a significant event during apoptosis signaling, regardless of the initiating stimulus. In this scenario oxidants act as second messengers, mediating the post-translational modification of specific regulatory proteins. The exact mechanism of this signaling is unclear, but increased understanding offers the potential to promote or inhibit apoptosis through modulating the redox environment of cells. Peroxiredoxins are thiol peroxidases that remove hydroperoxides, and are also emerging as important players in cellular redox signaling. This review discusses the potential role of peroxiredoxins in the regulation of apoptosis, and also their ability to act as biomarkers of redox changes during the initiation and progression of cell death. PMID- 26810077 TI - Residues from the thermal conversion of waste from the meat industry as a source of valuable macro- and micronutrients. AB - The increased consumption of meat (including poultry) observed over the last decade has led to the intensification of its production. With the production increase, the amount of generated waste also increases. Appropriate disposal of waste from the meat industry will significantly reduce the amount of such waste and its negative impact on the environment. The paper presents a method for the thermal neutralisation of feathers, poultry litter and meat and bone meal (MBM). Waste incineration was carried out in a stationary electric furnace, at a temperature varying in the range of 600-900 degrees C. The resulting ashes were characterised by a high percentage of phosphorus (30-170 g/kg ash), calcium (20 360 g/kg ash) and other valuable macro- and micronutrients like copper, iron, manganese and zinc. The ashes produced during the thermal treatment are safe in terms of sanitary and can be used as additives enriching the fertilisers and soil improvers. PMID- 26810078 TI - Fungal biodiversity to biotechnology. AB - Fungal habitats include soil, water, and extreme environments. With around 100,000 fungus species already described, it is estimated that 5.1 million fungus species exist on our planet, making fungi one of the largest and most diverse kingdoms of eukaryotes. Fungi show remarkable metabolic features due to a sophisticated genomic network and are important for the production of biotechnological compounds that greatly impact our society in many ways. In this review, we present the current state of knowledge on fungal biodiversity, with special emphasis on filamentous fungi and the most recent discoveries in the field of identification and production of biotechnological compounds. More than 250 fungus species have been studied to produce these biotechnological compounds. This review focuses on three of the branches generally accepted in biotechnological applications, which have been identified by a color code: red, green, and white for pharmaceutical, agricultural, and industrial biotechnology, respectively. We also discuss future prospects for the use of filamentous fungi in biotechnology application. PMID- 26810079 TI - Efficient butanol-ethanol (B-E) production from carbon monoxide fermentation by Clostridium carboxidivorans. AB - The fermentation of waste gases rich in carbon monoxide using acetogens is an efficient way to obtain valuable biofuels like ethanol and butanol. Different experiments were carried out with the bacterial species Clostridium carboxidivorans as biocatalyst. In batch assays with no pH regulation, after complete substrate exhaustion, acetic acid, butyric acid, and ethanol were detected while only negligible butanol production was observed. On the other side, in bioreactors, with continuous carbon monoxide supply and pH regulation, both C2 and C4 fatty acids were initially formed as well as ethanol and butanol at concentrations never reported before for this type of anaerobic bioconversion of gaseous C1 compounds, showing that the operating conditions significantly affect the metabolic fermentation profile and butanol accumulation. Maximum ethanol and butanol concentrations in the bioreactors were obtained at pH 5.75, reaching values of 5.55 and 2.66 g/L, respectively. The alcohols were produced both from CO fermentation as well as from the bioconversion of previously accumulated acetic and butyric acids, resulting in low residual concentrations of such acids at the end of the bioreactor experiments. CO consumption was often around 50% and reached up to more than 80%. Maximum specific rates of ethanol and butanol production were reached at pH 4.75, with values of 0.16 g/h*g of biomass and 0.07 g/h*g of biomass, respectively, demonstrating that a low pH was more favorable to solventogenesis in this process, although it negatively affects biomass growth which does also play a role in the final alcohol titer. PMID- 26810080 TI - Biomethane production and microbial community response according to influent concentration of molasses wastewater in a UASB reactor. AB - This study aimed to investigate the interaction between methane production performance and active microbial community dynamics at different loading rates by increasing influent substrate concentration. The model system was an upflow anaerobic sludge blanket (UASB) reactor using molasses wastewater. The active microbial community was analyzed using a ribosomal RNA-based approach in order to reflect active members in the UASB system. The methane production rate (MPR) increased with an increase in organic loading rate (OLR) from 3.6 to 5.5 g COD.L( 1).day(-1) and then it decreased with further OLR addition until 9.7 g COD.L( 1).day(-1). The UASB reactor achieved a maximum methane production rate of 0.48 L.L(-1).day(-1) with a chemical oxygen demand (COD) removal efficiency of 91.2 % at an influent molasses concentration of 16 g COD.L(-1) (OLR of 5.5 g COD.L( 1).day(-1)). In the archaeal community, Methanosarcina was predominant irrespective of loading rate, and the relative abundance of Methanosaeta increased with loading rate. In the bacterial community, Firmicutes and Eubacteriaceae were relatively abundant in the loading conditions tested. The network analysis between operation parameters and microbial community indicated that MPR was positively associated with most methanogenic archaea, including the relatively abundant Methanosarcina and Methanosaeta, except Methanofollis. The most abundant Methanosarcina was negatively associated with Bifidobacterium and Methanosaeta, whereas Methanosaeta was positively associated with Bifidobacterium. PMID- 26810081 TI - Assessment of heat tolerance and production performance of Aardi, Damascus, and their crossbred goats. AB - The question of whether the adaptability and production performance in goats may be enhanced using a crossbreeding program between bucks of a native and heat tolerant breed and does of an exotic and dual-purpose breed was approached and examined herein by comparing purebred Aardi and Damascus goats and their crossbred lines (i.e., (1)/2 Aardi (1)/2 Damascus (1/2A1/2D) and (1)/4 Aardi (3)/4 Damascus (1/4A3/4D)) reared in a region characterized by dry and hot bioclimatic conditions. Twenty-four male 6-month-old kids randomly segregated into four groups (six replicates/group) were used for the experiment. Climatic, thermo-physiological, biophysiological, metabolic, blood hematological, and biochemical measurements were all determined. The obtained results indicated that such a program was proven to be successful. This conclusion was demonstrated by the findings that crossbred goats (i.e., (1)/2A(1)/2D and (1)/4A(3)/4D) under such bioclimatic conditions were able to show (P < 0.05) higher heat tolerance capabilities compared to purebred Damascus goats as well as manifested (P < 0.05) higher production performance compared to the purebred Aardi goats. Accordingly, these evidences could emphasize that the crossbreeding may enable these animals to display a simultaneous improvement of both traits by the possible benefits that could arise from heterosis and breed complementarity. Researches dealing with this aspect may very well improve our understanding of goat's production and welfare under harsh environmental conditions. Future studies should include an economic analysis of traits that have the potential to impact the overall profitability to a vertically coordinated system. PMID- 26810082 TI - Variability in the chemistry of private drinking water supplies and the impact of domestic treatment systems on water quality. AB - Tap water from 497 properties using private water supplies, in an area of metalliferous and arsenic mineralisation (Cornwall, UK), was measured to assess the extent of compliance with chemical drinking water quality standards, and how this is influenced by householder water treatment decisions. The proportion of analyses exceeding water quality standards were high, with 65 % of tap water samples exceeding one or more chemical standards. The highest exceedances for health-based standards were nitrate (11 %) and arsenic (5 %). Arsenic had a maximum observed concentration of 440 ug/L. Exceedances were also high for pH (47 %), manganese (12 %) and aluminium (7 %), for which standards are set primarily on aesthetic grounds. However, the highest observed concentrations of manganese and aluminium also exceeded relevant health-based guidelines. Significant reductions in concentrations of aluminium, cadmium, copper, lead and/or nickel were found in tap waters where households were successfully treating low-pH groundwaters, and similar adventitious results were found for arsenic and nickel where treatment was installed for iron and/or manganese removal, and successful treatment specifically to decrease tap water arsenic concentrations was observed at two properties where it was installed. However, 31 % of samples where pH treatment was reported had pH < 6.5 (the minimum value in the drinking water regulations), suggesting widespread problems with system maintenance. Other examples of ineffectual treatment are seen in failed responses post-treatment, including for nitrate. This demonstrates that even where the tap waters are considered to be treated, they may still fail one or more drinking water quality standards. We find that the degree of drinking water standard exceedances warrant further work to understand environmental controls and the location of high concentrations. We also found that residents were more willing to accept drinking water with high metal (iron and manganese) concentrations than international guidelines assume. These findings point to the need for regulators to reinforce the guidance on drinking water quality standards to private water supply users, and the benefits to long-term health of complying with these, even in areas where treated mains water is widely available. PMID- 26810083 TI - The respiratory consequences of early-term birth and delivery by caesarean sections. AB - In England and Wales, 19% of live births in 2012 were at 37-38 weeks' gestation, equating to nearly 140 000 early-term births each year. Since caesarean sections (CS) are often performed at early-term gestations, this accounts for some of the increased proportion of the early-term births. Infants born early-term are at an increased risk of neonatal respiratory morbidity particularly if they are delivered by caesarean section. The long term lung function data are limited but available data suggest that early-term delivery is associated with respiratory morbidity in childhood. CS also appears to be associated with increased neonatal morbidity and future development of respiratory symptoms. However, future studies need to confirm the independent effects of caesarean sections and early-term deliveries particularly for long term outcomes as both are likely to affect the respiratory system differently. PMID- 26810086 TI - Fatal Babesia canis canis infection in a splenectomized Estonian dog. AB - A previously splenectomized dog from Estonia was presented with a sudden lack of appetite and discoloration of the urine. Despite supportive therapy, its condition deteriorated dramatically during 1 day. Severe thrombocytopenia and high numbers of protozoan hemoparasites were evident in blood smears, and the hematocrit dropped from 46 to 33 %. The dog was euthanized before specific antibabesial treatment was initiated. Blood samples from the dog and from two other dogs in the same household tested positive for Babesia using molecular methods, and the sequences of partial 18S rRNA gene confirmed the causative species as Babesia canis canis. The risk of severe, rapidly progressing babesiosis in splenectomized dogs merits awareness. PMID- 26810087 TI - Apoptosis and failure of checkpoint kinase 1 activation in human induced pluripotent stem cells under replication stress. AB - BACKGROUND: Human induced pluripotent stem (hiPS) cells have the ability to undergo self-renewal and differentiation similarly to human embryonic stem (hES) cells. We have recently shown that hES cells under replication stress fail to activate checkpoint kinase 1 (CHK1). They instead commit to apoptosis, which appears to be a primary defense mechanism against genomic instability. It is not known whether the failure of CHK1 activation and activation of apoptosis under replication stress is solely a feature of hES cells, or if it is a feature that can be extended to hiPS cells. METHODS: Here we generated integration-free hiPS cell lines by mRNA transfection, and characterised the cell lines. To investigate the mechanism of S phase checkpoint activation, we have induced replication stress by adding excess thymidine to the cell culture medium, and performed DNA content analysis, apoptosis assays and immunoblottings. RESULTS: We are showing that hiPS cells similarly to hES cells, fail to activate CHK1 when exposed to DNA replication inhibitors and commit to apoptosis instead. Our findings also suggest the Ataxia Telangiectasia Mutated pathway might be responding to DNA replication stress, resulting in apoptosis. CONCLUSION: Together, these data suggest that the apoptotic response was properly restored during reprogramming with mRNA, and that apoptosis is an important mechanism shared by hiPS and hES cells to maintain their genomic integrity when a replication stress occurs. PMID- 26810089 TI - A rare case of disseminated skin and mucosal necrobiotic xanthogranuloma and xanthoma. PMID- 26810098 TI - Physician Engagement in the Transformation of the Pediatric Patient Experience. PMID- 26810099 TI - 50 Years Ago in The Journal of Pediatrics: Scleroderma in Childhood. PMID- 26810100 TI - 50 Years Ago in The Journal of Pediatrics: The Nail-Patella Syndrome: Clinical and Genetic Aspects of 5 Kindreds with 38 Affected Family Members. PMID- 26810101 TI - 50 Years Ago in The Journal of Pediatrics: The Peripheral White Blood Count in Respirovirus Infection. PMID- 26810102 TI - 50 Years Ago in The Journal of Pediatrics: Virologic Studies of Exanthems. PMID- 26810103 TI - The "Invisible Children": Uncertain Future of Unaccompanied Minor Migrants in Europe. PMID- 26810104 TI - Success evaluation of the biological control of Fusarium wilts of cucumber, banana, and tomato since 2000 and future research strategies. AB - The Fusarium wilt caused by Fusarium oxysporum strains is the most devastating disease of cucumber, banana, and tomato. The biological control of this disease has become an attractive alternative to the chemical fungicides and other conventional control methods. In this review, the research trends and biological control efficiencies (BCE) of different microbial strains since 2000 are reviewed in detail, considering types of microbial genera, inoculum application methods, plant growth medium and conditions, inoculum application with amendments, and co inoculation of different microbial strains and how those affect the BCE of Fusarium wilt. The data evaluation showed that the BCE of biocontrol agents was higher against the Fusarium wilt of cucumber compared to the Fusarium wilts of banana and tomato. Several biocontrol agents mainly Bacillus, Trichoderma, Pseudomonas, nonpathogenic Fusarium, and Penicillium strains were evaluated to control Fusarium wilt, but still this lethal disease could not be controlled completely. We have discussed different reasons of inconsistent results and recommendations for the betterment of BCE in the future. This review provides knowledge of the biotechnology of biological control of Fusarium wilt of cucumber, banana, and tomato in a nut shell that will provide researchers a beginning line to start and to organize and plan research for the future studies. PMID- 26810105 TI - Australian and New Zealand Society for Geriatric Medicine Position Statement Abstract: Physical restraint use in older people. PMID- 26810107 TI - Enhanced photoresponse in dye-sensitized solar cells via localized surface plasmon resonance through highly stable nickel nanoparticles. AB - We demonstrated the localized surface plasmon resonance (LSPR) effect of Ni nanoparticles (NiNPs) on the performance of dye-sensitized solar cells (DSSCs). Our study revealed that NiNPs in a conventional I(-)/I3(-) electrolyte (NiNPs@I( )/I3(-)) increased the net optical absorption of a N719 dye over a broad wavelength range by LSPR, and concurrently improved the power conversion efficiency (PCE) in DSSCs. At an optimized concentration of the NiNPs@I(-)/I3(-) electrolyte (1 mg mL(-1)), N719-sensitized DSSCs with a photoanode thickness of ca. 2, 5, and 10 MUm, exhibited net PCEs of 2.32, 6.02, and 9.83%, respectively. These efficiencies were consistent with a net improvement of 43.2, 20.4, and 12.7%, respectively and were mainly attributed to a significant enhancement of the short circuit current density (Jsc) by the LSPR from the NiNPs. Similar effects were observed for cells sensitized by the N3, Ru505, and Z907 dyes. Furthermore, the NiNPs exhibited excellent resistance to corrosion from a conventional I(-)/I3(-) electrolyte over a period of 60 days. PMID- 26810108 TI - Laboratory prediction of primary postpartum haemorrhage: a comparative cohort study. AB - BACKGROUND: Postpartum haemorrhage (PPH) is the leading cause of maternal deaths, the world over. The aim of this study was to determine laboratory parameters that could serve as risk factors for primary PPH. METHODS: This comparative cohort study involved 350 pregnant women at term who were recruited consecutively from the Komfo Anokye Teaching Hospital, Kumasi, Ghana. PPH was defined as a measured blood loss >= 500 ml or enough to cause haemodynamic shock. Basic demographic data was gathered and blood was collected for laboratory assays before delivery. Univariate and multivariate logistic regression models were used to identify variables that were significantly associated with primary PPH. RESULTS: Of the total recruited study participants (350), five declined to participate and 74 went through caesarean section, episiotomy or instrumental deliveries and were excluded. Of the remaining (271) study participants who went through spontaneous vaginal delivery, fifty five (55) were diagnosed with primary PPH (Group 1) and the remaining 216 were those who did not have PPH (Group 2). Demographic characteristics did not differ between the two groups (P > 0.05). Univariate analysis showed that AST (P = 0.043), urea (P < 0.001), creatinine (P = 0.002), urea-to-creatinine ratio (P = 0.014) and the proportion of abnormal peripheral blood smear (P < 0.001) was higher among women in Group 1 compared to those in Group 2. Women in Group 1 had a significantly lower haemoglobin concentration (10.7 g/dL) compared to those in Group 2 (12.1g/dL). Upon multivariate analysis, an abnormal peripheral blood smear (AOR = 2.9672), Hb, (AOR = 0.5791), moderate to severe anaemia (Hb <10 g/dL) (AOR = 3.1385), Urea (AOR = 3.6435) and intra renal azotaemia (AOR = 0.1893) remained significant. CONCLUSION: Many laboratory parameters are associated with primary PPH but only a few are independent risk factors. A total clinical work-up including laboratory evaluation of the independent blood variables identified in this study will help a great deal to identify individuals at high risk for PPH. PMID- 26810110 TI - Higher prices, higher quality? Evidence from German nursing homes. AB - OBJECTIVES: This study investigates the relationship between prices and quality of 7400 German nursing homes. METHOD: We use a cross section of public quality reports for all German nursing homes, which had been evaluated between 2010 and 2013 by external institutions. Our analysis is based on multivariate regressions in a two stage least squares framework, where we instrument prices to explain their effect on quality controlling for income, nursing home density, demographics, labour market characteristics, and infrastructure at the regional level. RESULTS: Descriptive analysis shows that prices and quality do not only vary across nursing homes, but also across counties and federal states and that quality and prices correlate positively. Second, the econometric analysis, which accounts for the endogenous relation between negotiated price and reported quality, shows that quality indeed positively depends on prices. In addition, more places in nursing homes per people in need are correlated with both lower prices and higher quality. Finally, unobserved factors at the federal state level capture some of the variation of reported quality across nursing homes. CONCLUSION: Our results suggest that higher prices increase quality. Furthermore, since reported quality and prices vary substantially across federal states, we conclude that the quality and prices of long-term care facilities may well be compared within federal states but not across. PMID- 26810111 TI - [Nontuberculous mycobacterial pulmonary disease]. AB - Nontuberculous mycobacteria (NTM) are a group of biologically diverse, ubiquitous and naturally multi-drug resistant bacteria with facultative pathogenicity. Recent data suggest that their clinical significance is increasing worldwide and that susceptible individuals may be at risk for infection via contaminated surfaces and aerosols. These individuals often have a predisposition for chronic respiratory diseases, e. g. bronchiectasis, chronic obstructive pulmonary disease (COPD) and cystic fibrosis and these conditions frequently share the same unspecific signs and symptoms with NTM pulmonary disease (NTM-PD). As a consequence, the diagnosis of NTM-PD, which is established based on clinical, radiological and microbiological criteria, is often delayed. Treating NTM-PD is more demanding than treating pulmonary tuberculosis as therapy is generally more tedious, toxic and expensive as well as being prone to failure. Patient and pathogen-specific factors guide the choice of an appropriate antimicrobial combination regimen, which should comply with national and international recommendations. Adverse events are common, should be anticipated and closely monitored. If infections with infrequently encountered mycobacterial species and severe or refractory disease occur, an interdisciplinary approach should be used, involving infectious disease specialists, experienced thoracic surgeons and referral to an NTM specialist center. PMID- 26810112 TI - The impact of the Great Recession on mental health and its inequalities: the case of a Southern European region, 1997-2013. AB - BACKGROUND: Numerous studies have shown that macroeconomic changes have a great influence on health, prompting different concerns in recent literature about the effects of the current recession. The objective of the study was to assess the changes in the mental health of the working-age population in the Basque Country (Spain) and its social inequalities following the onset of the 2008 recession, with special focus on the role of unemployment. METHODS: Repeated cross-sectional study on the population aged 16-64, using four Basque Health Surveys (1997-2013). Age-adjusted prevalences of poor mental health and incremental prevalence ratios (working status and social class adjusted) between years were calculated. Absolute/relative measures of social inequalities were also calculated. RESULTS: From 2008, there was a clear deterioration in the mental health, especially among men. Neither changes in employment status nor social class accounted for these changes. In men, the deterioration affected all working status categories, except the retired but significant changes occurred only among the employed. In women, poor mental health significantly increased among the unemployed. Students were also especially affected. Relative inequalities increased only in men. CONCLUSIONS: The Great Recession is being accompanied by adverse effects on mental health, which cannot be fully explained by the increase of unemployment. Public health professionals should closely monitor the medium and long-term effects of the crisis as these may emerge only many years after the onset of recessions. PMID- 26810114 TI - Fluoride-assisted synthesis of bimodal microporous SSZ-13 zeolite. AB - The presence of small amount of fluoride in alkaline hydrothermal synthesis of SSZ-13 zeolite yields bimodal microporous particles with substantially improved performance in the methanol-to-olefins (MTO) reaction. Hydrocarbon uptake measurements and fluorescence microspectroscopy of spent catalysts demonstrate enhanced diffusion through micropores at the grain boundaries of nanocrystals running through the zeolite particles. Fluoride-assisted SSZ-13 synthesis is a cheap and scalable approach to optimize the performance of MTO zeolite catalysts. PMID- 26810113 TI - Membranous glomerulonephritis: histological and serological features to differentiate cancer-related and non-related forms. AB - Membranous nephropathy is a frequent cause of nephrotic syndrome in adults. In most patients, it appears as a primary renal disease but in about 20 % of cases membranous nephropathy is associated with systemic conditions such as systemic lupus erythematosus, infections or cancer, or with drug exposure. Reliable differentiation between primary and secondary membranous nephropathy has important implications for the patient, because of different therapeutic approaches between the different forms. The recent in vivo definition of glomerular targets of autoimmunity in idiopathic membranous nephropathy represented a real breakthrough and nowadays more than one podocyte antigen is considered in some way implicated in the pathogenesis of human membranous nephropathy. Specific antibodies against all these components have been detected in serum of patients and could become biomarkers of membranous nephropathy and/or of disease activity. In this brief review, we discuss the usefulness of newly described autoantibodies in the differential diagnosis of secondary membranous nephropathy. Histological clues for recognizing the two pathological entities are also analysed with regard to the available scientific evidence on this issue. Our evaluation shows that more research is needed to identify the best approach to reach a correct diagnosis of primary or secondary membranous nephropathy. PMID- 26810116 TI - Assessing Work Disability After Radical Prostatectomy. PMID- 26810118 TI - WHO calls for tax on sugary drinks to tackle child obesity. PMID- 26810119 TI - Factors associated to recurrent wheezing in infants under one year of age in the province of Salamanca, Spain: Is intervention possible? A predictive model. AB - OBJECTIVES: Wheezing is a very common problem in infants in the first months of life. The objective of this study is to identify risk factors that may be acted upon in order to modify the evolution of recurrent wheezing in the first months of life, and to develop a model based on certain factors associated to recurrent wheezing in nursing infants capable of predicting the probability of developing recurrent wheezing in the first year of life. METHODS: The sample was drawn from a cross-sectional, multicentre, descriptive epidemiological study based on the general population. A total of 1164 children were studied, corresponding to a questionnaire response rate of 71%. The questionnaire of the Estudio Internacional de Sibilancias en Lactantes (EISL) was used. Multiple logistic regression analysis was used to estimate the probability of developing recurrent wheezing and to quantify the contribution of each individual variable in the presence of the rest. RESULTS: Infants presenting eczema and attending nursery school, with a mother who has asthma, smoked during the third trimester of pregnancy, and did not consume a Mediterranean diet during pregnancy were found to have a probability of 79.7% of developing recurrent wheezing in the first year of life. In contrast, infants with none of these factors were seen to have a probability of only 4.1% of developing recurrent wheezing in the first year of life. These results in turn varied according to modifications in the risk or protective factors. CONCLUSIONS: The mathematical model estimated the probability of developing recurrent wheezing in infants under one year of age in the province of Salamanca (Spain), according to the risk or protective factors associated to recurrent wheezing to which the infants are or have been exposed. PMID- 26810123 TI - Perceived social support and health-related quality of life in AYA cancer survivors and controls. AB - BACKGROUND: This study compared education levels, health-related quality of life (HRQoL) and perceived social support of adolescent and young adult (AYA) cancer survivors with those of a control group of peers with no history of serious illness. The links between socio-demographic and medical factors and AYA cancer survivor outcomes were investigated. METHODS: The participants included AYA cancer survivors (n = 205) recruited during follow-up visits, and AYA peers (n = 205) recruited from the secondary schools, youth groups and universities. All of the participants filled in self-report questionnaires regarding HRQoL and perceived social support. In addition, medical and socio-demographic information was collected. RESULTS: There were statistically significant differences between survivors and controls in terms of education level, HRQoL and perceived social support. Cancer survivors attended school for fewer years had a more positive perception of their health and a lower level of perceived social support provided by family, friends and significant others than controls. The results showed that female gender, the diagnosis of haematological disorder, haematopoietic stem cell transplantation and a shorter off-treatment period are risk variables for poorer HRQoL and social functioning in AYA cancer survivors. CONCLUSIONS: Adolescent and young adult cancer survivors perceived a better quality of life than controls, especially those treated for haematological disorders or with a shorter off treatment period. Future studies should aim to understand better this positive self-reported phenomenon, as well as investigating post-traumatic growth using qualitative narratives. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26810124 TI - Reverse Sural Artery Island Flap With Skin Extension Along the Pedicle. AB - The distally based sural flap is an efficient flap for reconstruction of soft tissues defects of lower limb. The unstable vascular pedicle, however, is prone to compression by the subcutaneous tunnel, especially when a long pedicle covers the distal area of the foot. The aim of the present study was to introduce a modified surgical technique that leaves the skin extension over the pedicle and to report the clinical results of this modification. A total of 25 consecutive patients with a mean age of 51.7 +/- 14.7 years underwent surgery. We modified the conventional sural flap technique by leaving a skin extension over the entire length of the pedicle, creating a fasciocutaneous vascular pedicle. The postoperative flap survival rates, complications, and the characteristics of the flaps such as flap size, pedicle length, and the most distal area that could be covered with this modification, were reviewed. At the last clinical follow-up examination, all the flaps survived, although partial necrosis was observed in 2 (8%) cases. Four cases of venous congestion developed but healed without additional complications. The mean flap size was 5.9 +/- 1.8 * 9.2 +/- 2.7 cm. With this modification, the sural flap could cover the defect located in extreme distal areas, such as the medial forefoot and dorsum of the first metatarsophalangeal joint, with a longer pedicle (<=27 cm) in 7 patients (28%). A skin extension along the pedicle achieved the favorable survival rate of the sural flap and successfully extended the surgical indications to more distal areas. PMID- 26810125 TI - Fill in the Blanks: A Tale of Data Gone Missing. AB - In studies, we often encounter patients for whom data is missing. More than a nuisance, such missing data can seriously impact our analyses. I discuss here some methods to handle these situations. PMID- 26810126 TI - Vascularized Pedicled Fibula Onlay Bone Graft Augmentation for Complicated Tibiotalocalcaneal Arthrodesis With Retrograde Intramedullary Nail Fixation: A Case Series. AB - Tibiotalocalcaneal arthrodesis stabilized with retrograde intramedullary nail fixation is associated with a high incidence of complications. This is especially true when performed with a bulk structural allograft and poor soft tissue quality. In select high-risk limb salvage cases, we have augmented tibiotalocalcaneal arthrodesis procedures stabilized using retrograde intramedullary nail fixation with a vascularized pedicled fibular onlay bone graft. We present the data from 10 such procedures with a mean follow-up period of 10.9 +/- 5.4 (range 6 to 20) months involving 10 patients (9 males and 1 female). The etiology was avascular osteonecrosis of the talus and/or distal tibia and a resultant large volume cavitary bone defect (8 ankles), severe equinocavovarus contracture (1 ankle), and failed total ankle replacement (1 ankle). A frozen femoral head bulk allograft was used twice, a whole frozen talus allograft once, and a freeze-dried calcaneal allograft once. The fibula was mobilized with intact musculoperiosteal perforating branches of the peroneal artery as a vascularized pedicle onlay bone graft fixated with a screw and washer construct. The mean fibular graft length was 10.2 +/- 2.3 cm. The mean interval to radiographic fusion was 2.6 +/- 0.6 months and to weightbearing was 3.1 +/- 1.4 months. Two stable bulk allograft-host bone and fibular graft-host bone nonunions occurred after intramedullary nail hardware failure. Tibiotalocalcaneal arthrodesis augmented by vascularized pedicled fibular graft stabilized with retrograde compression intramedullary nail fixation offers a reliable option for complex salvage situations when few other options exist. PMID- 26810127 TI - Comparison Between Sinus Tarsi Approach and Extensile Lateral Approach for Treatment of Closed Displaced Intra-Articular Calcaneal Fractures: A Multicenter Prospective Study. AB - The purpose of our investigation was to prospectively review and compare the early outcomes of Sanders II and III closed displaced intra-articular calcaneal fractures (DIACFs) in a group of patients treated by open reduction and internal fixation with plate and screws using the extended lateral approach or the sinus tarsi approach (STA). Thirty-eight patients with DIACFs were prospectively enrolled and operatively treated using either the extended lateral approach or the STA. Patients underwent a careful clinical and radiographic examination and were evaluated according to the American Orthopaedic Foot and Ankle Society score, visual analog scale, and the Foot Function Index. The results from our study showed similar clinical and radiographic outcomes between the 2 groups. In our series, Sanders II and III DIACFs were sufficiently exposed using the STA to achieve anatomic reduction and stable fixation. The STA group had a lower incidence of wound complications (p >= .05), the surgical procedure was faster, and the waiting time to surgery was shorter (p <= .05). Despite the limited number of patients and the short follow-up period, our results suggest that the STA is a useful method for the treatment of DIACFs, with a low incidence of complications and results comparable to those for patients treated using the extended lateral approach. PMID- 26810128 TI - Is Subtalar Joint Cartilage Resection Necessary for Tibiotalocalcaneal Arthrodesis via Intramedullary Nail? A Multicenter Evaluation. AB - Tibiotalocalcaneal arthrodesis with intramedullary nailing is traditionally performed with formal preparation of both the subtalar and ankle joints. However, we believe that subtalar joint preparation is not necessary to achieve satisfactory outcomes in patients undergoing tibiotalocalcaneal arthrodesis with a retrograde intramedullary nail. The primary aim of the present retrospective study was to evaluate the outcomes of patients who had undergone tibiotalocalcaneal arthrodesis with an intramedullary nail without formal subtalar joint cartilage resection. A multicenter medical record review was performed to identify consecutive patients. Pain was assessed using a visual analog scale, and osseous union at the tibiotalar joint was defined as bony trabeculation across the arthrodesis site on all 3 radiographic views. Progression of joint deterioration was evaluated across time at the subtalar joint, using a modified grading system developed by Takakura et al. Forty consecutive patients (aged 61.9 +/- 12.9 years; 17 men) met the inclusion and exclusion criteria. Compared with the pain reported preoperatively (6.4 +/- 2.7), a statistically significant decline was seen in the pain experienced after surgery (1.2 +/- 1.8; p < .001). The mean time to consolidated arthrodesis at the ankle joint was 3.8 +/- 1.5 months. A statistically significant increase in deterioration at the subtalar joint was observed across time [t(36) = -6.200, p < .001]. Compared with previously published data of subtalar joint cartilage resection, the present study has demonstrated a similar decline in pain, with a high rate of union, and also a decrease in operative time when preparation of the subtalar joint was not performed. PMID- 26810129 TI - Charcot Neuroarthropathy in Patients With Diabetes: An Updated Systematic Review of Surgical Management. AB - Charcot neuroarthropathy (CN) of the foot and ankle is a demanding clinical dilemma, and surgical management can be very complicated. Historically, the evidence guiding surgical management of CN has been small retrospective case series and expert opinions. The purpose of the present report was to provide a systematic review of studies published from 2009 to 2014 and to review the indications for surgery. A Medline search was performed, and a systematic review of studies discussing the surgical management of CN was undertaken. Thirty reports fit the inclusion criteria for our study, including 860 patients who had undergone a surgical procedure for the treatment of CN. The surgical procedures included amputation, arthrodesis, debridement of ulcers, drainage of infections, and exostectomy. The midfoot was addressed in 26.9% of cases, the hindfoot in 41.6%, and the ankle in 38.4%. Of the 30 studies, 24 were retrospective case series (level 4), 4 were controlled retrospective studies (level 3), and 2 were level II studies. The overall amputation rate was 8.9%. The quality of the published data on the surgical management of CN has improved during the past several years. Evidence concerning the timing of treatment and the use of different fixation methods remains inconclusive. PMID- 26810130 TI - Low Rates of Adoption and Implementation of Rapid HIV Testing in Substance Use Disorder Treatment Programs. AB - INTRODUCTION: Rapid HIV testing (RHT) greatly increases the proportion of clients who learn their test results. However, existing studies have not examined the adoption and implementation of RHT in programs treating persons with substance use disorders, one of the population groups at higher risk for HIV infection. METHODS: We examined 196 opioid treatment programs (OTPs) using data from the 2011 National Drug Abuse Treatment System Survey (NDATSS). We used logistic regressions to identify client and organizational characteristics of OTPs associated with availability of on-site RHT. We then used zero-inflated negative binomial regressions to measure the association between the availability of RHT on-site and the number of clients tested for HIV. RESULTS: Only 31.6% of OTPs offered on-site rapid HIV testing to their clients. Rapid HIV testing was more commonly available on-site in larger, publicly owned and better-staffed OTPs. On the other hand, on-site rapid HIV testing was less common in OTPs that prescribed only buprenorphine as a method of opioid dependence treatment. The availability of rapid HIV testing on-site reduced the likelihood that an OTP did not test any of its clients during the prior year. But on-site availability rapid HIV testing was not otherwise associated with an increased number of clients tested for HIV at an OTP. CONCLUSIONS: New strategies are needed to a) promote the adoption of rapid HIV testing on-site in substance use disorder treatment programs and b) encourage substance use disorder treatment providers to offer rapid HIV testing to their clients when it is available. PMID- 26810131 TI - Gender Differences in the Life Concerns of Persons Seeking Alcohol Detoxification. AB - BACKGROUND: This study explored the life concerns of persons seeking alcohol detoxification, a group with multiple life and psychosocial challenges. Gender may be an important contributor to the particular life concerns of persons with alcohol use disorders. METHODS: Using a 32-item, previously-validated life concerns survey that captures ten conceptual domains, we interviewed persons entering inpatient alcohol detoxification asking them to rate their level of concern about health and welfare items. RESULTS: Participants (n=189) were 27% female, with a mean age of 43.5 years. Overall, concern about alcohol problems was perceived as the most serious, followed by mental health, cigarette smoking, financial, and relationship problems. Men were significantly more concerned than women about six of the ten domains including money, drug use, transmissible diseases, and physical illness. CONCLUSIONS: Recognition of the daily worries of persons seeking inpatient alcohol detoxification persons could allow providers to better tailor their services to the context of their patients' lives. Focusing on pressing life concerns such as mental health, financial, relationship problems, and other drug use may influence detoxification services and aftercare treatment choices. PMID- 26810132 TI - Genetic markers predicting sulphonylurea treatment outcomes in type 2 diabetes patients: current evidence and challenges for clinical implementation. AB - The clinical response to sulphonylurea, an oral antidiabetic agent often used in combination with metformin to control blood glucose in type 2 diabetes (T2DM) patients, has been widely associated with a number of gene polymorphisms, particularly those involved in insulin release. We have reviewed the genetic markers of CYP2C9, ABCC8, KCNJ11, TCF7L2 (transcription factor 7-like 2), IRS-1 (insulin receptor substrate-1), CDKAL1, CDKN2A/2B, KCNQ1 and NOS1AP (nitric oxide synthase 1 adaptor protein) genes that predict treatment outcomes of sulphonylurea therapy. A convincing pattern for poor sulphonylurea response was observed in Caucasian T2DM patients with rs7903146 and rs1801278 polymorphisms of the TCF7L2 and IRS-1 genes, respectively. However, limitations in evaluating the available studies including dissimilarities in study design, definitions of clinical end points, sample sizes and types and doses of sulphonylureas used as well as ethnic variability make the clinical applications challenging. Future studies need to address these limitations to develop personalized sulphonylurea medicine for T2DM management. PMID- 26810133 TI - ABCC3 genetic variants are associated with postoperative morphine-induced respiratory depression and morphine pharmacokinetics in children. AB - Respiratory depression (RD) is a serious side effect of morphine and detrimental to effective analgesia. We reported that variants of the ATP binding cassette gene ABCC3 (facilitates hepatic morphine metabolite efflux) affect morphine metabolite clearance. In this study of 316 children undergoing tonsillectomy, we found significant association between ABCC3 variants and RD leading to prolonged postoperative care unit stay (prolonged RD). Allele A at rs4148412 and allele G at rs729923 caused a 2.36 (95% CI=1.28-4.37, P=0.0061) and 3.7 (95% CI 1.47-9.09, P=0.0050) times increase in odds of prolonged RD, respectively. These clinical associations were supported by increased formation clearance of morphine glucuronides in children with rs4148412 AA and rs4973665 CC genotypes in this cohort, as well as an independent spine surgical cohort of 67 adolescents. This is the first study to report association of ABCC3 variants with opioid-related RD, and morphine metabolite formation (in two independent surgical cohorts). PMID- 26810134 TI - ABCG2 loss-of-function polymorphism predicts poor response to allopurinol in patients with gout. AB - Many patients fail to achieve the recommended serum urate (SU) target (<6 mgdl-1) with allopurinol. The aim of our study was to examine the association of ABCG2 with SU target in response to standard doses of allopurinol using a cohort with confirmed adherence. Good response was defined as SU<6 mgdl-1 on allopurinol ?300 mgd-1 and poor response as SU?6 mgdl-1 despite allopurinol >300 mgd-1. Adherence was confirmed by oxypurinol concentrations. ABCG2 genotyping was performed using pre-designed single nucleotide polymorphism (SNP) TaqMan assays. Of 264 patients, 120 were good responders, 68 were poor responders and 76 were either non-adherent or could not be classified. The minor allele of ABCG2 SNP rs2231142 conferred a significantly increased risk of poor response to allopurinol (odds ratio=2.71 (1.70-4.48), P=6.0 * 10-5). This association remained significant after adjustment for age, sex, body mass index, ethnicity, estimated glomerular filtration rate, diuretic use and SU off urate-lowering therapy. ABCG2 rs2231142 predicts poor response to allopurinol, as defined by SU?6 mgdl-1 despite allopurinol >300 mgd-1. PMID- 26810135 TI - Impact of germline and somatic missense variations on drug binding sites. AB - Advancements in next-generation sequencing (NGS) technologies are generating a vast amount of data. This exacerbates the current challenge of translating NGS data into actionable clinical interpretations. We have comprehensively combined germline and somatic nonsynonymous single-nucleotide variations (nsSNVs) that affect drug binding sites in order to investigate their prevalence. The integrated data thus generated in conjunction with exome or whole-genome sequencing can be used to identify patients who may not respond to a specific drug because of alterations in drug binding efficacy due to nsSNVs in the target protein's gene. To identify the nsSNVs that may affect drug binding, protein-drug complex structures were retrieved from Protein Data Bank (PDB) followed by identification of amino acids in the protein-drug binding sites using an occluded surface method. Then, the germline and somatic mutations were mapped to these amino acids to identify which of these alter protein-drug binding sites. Using this method we identified 12 993 amino acid-drug binding sites across 253 unique proteins bound to 235 unique drugs. The integration of amino acid-drug binding sites data with both germline and somatic nsSNVs data sets revealed 3133 nsSNVs affecting amino acid-drug binding sites. In addition, a comprehensive drug target discovery was conducted based on protein structure similarity and conservation of amino acid-drug binding sites. Using this method, 81 paralogs were identified that could serve as alternative drug targets. In addition, non-human mammalian proteins bound to drugs were used to identify 142 homologs in humans that can potentially bind to drugs. In the current protein-drug pairs that contain somatic mutations within their binding site, we identified 85 proteins with significant differential gene expression changes associated with specific cancer types. Information on protein-drug binding predicted drug target proteins and prevalence of both somatic and germline nsSNVs that disrupt these binding sites can provide valuable knowledge for personalized medicine treatment. A web portal is available where nsSNVs from individual patient can be checked by scanning against DrugVar to determine whether any of the SNVs affect the binding of any drug in the database. PMID- 26810136 TI - Sunitinib-induced hypertension in CYP3A4 rs4646437 A-allele carriers with metastatic renal cell carcinoma. AB - The single nucleotide polymorphism (SNP) rs4646437G>A in CYP3A4 was suggested to be related to sunitinib toxicity. Our objective was to perform an in-depth investigation of the association between this SNP and sunitinib toxicity and efficacy using a large cohort of metastatic renal cell carcinoma (mRCC) patients. We collected DNA and clinical information of mRCC patients treated with sunitinib. SNP rs4646437 in CYP3A4 was tested for associations with toxicity using logistic regression. Cox regression modeling was used for association analysis of rs4646437 with progression-free survival (PFS) and overall survival (OS). In a total of 287 patients, the A-allele of CYP3A4 rs4646437 was associated with an increased risk for hypertension (odds ratio=2.4, 95% confidence interval: 1.1-5.2, P=0.021) and showed no significant association with PFS or OS. In conclusion, hypertension is more likely to occur in A-allele carriers of the CYP3A4 rs4646437 variant in our cohort of mRCC patients treated with sunitinib. PMID- 26810138 TI - DCIS of the breast: The value of preoperative MRI. AB - INTRODUCTION: Ductal carcinoma in situ (DCIS) of the breast is commonly treated surgically. The intent of this study was to evaluate whether preoperative MRI could add to mammography in predicting the extent of the disease. METHODS: A series of patients with DCIS attending our surgical clinic for preoperative assessment were offered MRI as part of a prospective study. The extent of the disease indicated by mammography and MRI was compared with histopathology after definitive treatment. The null hypothesis was that MRI does not add to mammography in accurately predicting disease extent. RESULTS: Fifty patients make up the basis of this report. Mammography was concordant with the pathology in 31/50. MRI and mammography combined were concordant in 43/50. This is a statistically significant difference (P = 0.01, Fisher's exact test). Upstaging to mastectomy by MRI was correct in 7/8 patients, but downstaging was correct in only 2/4. CONCLUSIONS: The null hypothesis is rejected. MRI does add to mammography in accurately predicting the extent of DCIS. Upstaging by MRI is usually reliable. PMID- 26810137 TI - Pharmacogenetics of methylphenidate response and tolerability in attention deficit/hyperactivity disorder. AB - Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder. However, a considerable interindividual variability exists in clinical outcome, which may reflect underlying genetic influences. We analyzed 57 single-nucleotide polymorphisms in 9 dopamine-related candidate genes (TH, DBH, COMT, DAT1 and DRD1-5) as potential predictors of MPH efficacy and tolerability, and we considered prenatal and perinatal risk factors as environmental hazards that may influence treatment effects in a gene-by-environment analysis. Our results provide evidence for the contribution of DRD3 (P=0.041; odds ratio (OR)=4.00), DBH (P=0.032; OR=2.85), TH (P=5.5e-03; OR=4.34) and prenatal smoking (P=1.7e-03; OR=5.10) to the clinical efficacy of MPH, with a higher risk for treatment failure in genetically susceptible subjects whose mother smoked during pregnancy. Adverse events after MPH treatment were significantly associated with variation in DBH (P=6.4e-03; OR=0.28) and DRD2 (P=0.047; OR=3.76). This study suggests that the dopaminergic system together with prenatal smoking exposure may moderate MPH treatment effects. PMID- 26810139 TI - Automated Remote Monitoring of Depression: Acceptance Among Low-Income Patients in Diabetes Disease Management. AB - BACKGROUND: Remote patient monitoring is increasingly integrated into health care delivery to expand access and increase effectiveness. Automation can add efficiency to remote monitoring, but patient acceptance of automated tools is critical for success. From 2010 to 2013, the Diabetes-Depression Care-management Adoption Trial (DCAT)-a quasi-experimental comparative effectiveness research trial aimed at accelerating the adoption of collaborative depression care in a safety-net health care system-tested a fully automated telephonic assessment (ATA) depression monitoring system serving low-income patients with diabetes. OBJECTIVE: The aim of this study was to determine patient acceptance of ATA calls over time, and to identify factors predicting long-term patient acceptance of ATA calls. METHODS: We conducted two analyses using data from the DCAT technology facilitated care arm, in which for 12 months the ATA system periodically assessed depression symptoms, monitored treatment adherence, prompted self-care behaviors, and inquired about patients' needs for provider contact. Patients received assessments at 6, 12, and 18 months using Likert-scale measures of willingness to use ATA calls, preferred mode of reach, perceived ease of use, usefulness, nonintrusiveness, privacy/security, and long-term usefulness. For the first analysis (patient acceptance over time), we computed descriptive statistics of these measures. In the second analysis (predictive factors), we collapsed patients into two groups: those reporting "high" versus "low" willingness to use ATA calls. To compare them, we used independent t tests for continuous variables and Pearson chi-square tests for categorical variables. Next, we jointly entered independent factors found to be significantly associated with 18-month willingness to use ATA calls at the univariate level into a logistic regression model with backward selection to identify predictive factors. We performed a final logistic regression model with the identified significant predictive factors and reported the odds ratio estimates and 95% confidence intervals. RESULTS: At 6 and 12 months, respectively, 89.6% (69/77) and 63.7% (49/77) of patients "agreed" or "strongly agreed" that they would be willing to use ATA calls in the future. At 18 months, 51.0% (64/125) of patients perceived ATA calls as useful and 59.7% (46/77) were willing to use the technology. Moreover, in the first 6 months, most patients reported that ATA calls felt private/secure (75.9%, 82/108) and were easy to use (86.2%, 94/109), useful (65.1%, 71/109), and nonintrusive (87.2%, 95/109). Perceived usefulness, however, decreased to 54.1% (59/109) in the second 6 months of the trial. Factors predicting willingness to use ATA calls at the 18-month follow-up were perceived privacy/security and long term perceived usefulness of ATA calls. No patient characteristics were significant predictors of long-term acceptance. CONCLUSIONS: In the short term, patients are generally accepting of ATA calls for depression monitoring, with ATA call design and the care management intervention being primary factors influencing patient acceptance. Acceptance over the long term requires that the system be perceived as private/secure, and that it be constantly useful for patients' needs of awareness of feelings, self-care reminders, and connectivity with health care providers. TRIAL REGISTRATION: ClinicalTrials.gov NCT01781013; https://clinicaltrials.gov/ct2/show/NCT01781013 (Archived by WebCite at http://www.webcitation.org/6e7NGku56). PMID- 26810140 TI - Retrospective analysis of adult patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic cell transplantation: A multicenter experience of daily practice. AB - Compared to pediatric age group, the prognosis of adult acute lymphoblastic leukemia (ALL) is still dismal even in patients receiving allogeneic hematopoietic cell transplantation (AHCT). We retrospectively analyzed 205 adults (male: 122; female: 83) with ALL who underwent AHCT. Median age of patients was 28 (18-59). Fifty-two patients had Ph(+) ALL. The estimated relapse-free and overall survival (OS) of the study cohort at 1, 2 and 3 years were 52.3%/63.9%, 42.9%/49.5% and 39.9%/45.6%, respectively. On multivariate analysis, first complete remission at the time of AHCT, TBI-based conditioning and development of chronic graft-versus-host disease were only factors, which were significantly associated with prolonged OS. PMID- 26810141 TI - Primary central nervous system lymphoma in daily practice and the role of autologous stem cell transplantation in relapsed disease: A retrospective multicenter study. AB - We investigated the course of 54 patients presenting with primary central nervous system lymphoma, who were treated in daily practice. The patients were treated with chemotherapy and/or radiotherapy and/or intrathecal chemotherapy. At a median follow-up period of 23 months (range 1-71), median relapse-free survival (RFS) and overall survival (OS) were not reached. Estimated 2-year RFS and OS rates were 42% and 48%, respectively. Ten relapsed PCNSL patients underwent ASCT. Complete remission rate of these patients was 40%, with 20% treatment-related mortality. Estimated 2-year RFS and OS rates were 37% and 40%, respectively. The prognosis of patients with PCNSL, who received off-study treatment, is still dismal. PMID- 26810142 TI - ABO blood group mismatched hematopoietic stem cell transplantation. AB - Apart from solid organ transplantations, use of ABO-blood group mismatched (ABO mismatched) donors is acceptable in hematopoietic stem cell transplantation (HSCT) patients. About 20-40% of allogeneic HSCT recipients will receive grafts from ABO-mismatched donors. ABO incompatible HSCT procedures are associated with immediate and late consequences, including but not restricted to acute or delayed hemolytic reactions, delayed red blood cell recovery, pure red cell aplasia and graft-versus-host disease. This review summarizes the current knowledge about consequences of ABO-mismatched HSCT in terms of associated complications and will evaluate its impact on important outcome parameters of HSCT. PMID- 26810143 TI - Fluorine substitution influence on benzo[2,1,3]thiadiazole based polymers for field-effect transistor applications. AB - Four conjugated copolymers with a donor/acceptor architecture comprising 4,4 dihexadecyl-4H-cyclopenta[1,2-b:5,4-b']dithiophene as the donor structural unit and benzo[2,1,3]thiadiazole fragments with varying degrees of fluorination as the acceptor structural units have been synthesized and characterized. It has been shown that the energy levels were decreased after the fluorine substitution. The field-effect charge carrier mobility was similar for all polymers with less than an order of magnitude difference between different acceptor units. PMID- 26810144 TI - Synthesis and Biological Evaluation of 2-Oxo/Thioxoquinoxaline and 2 Oxo/Thioxoquinoxaline-Based Nucleoside Analogues. AB - Several O- and S-quinoxaline glycosides have been prepared by glycosidation of 3 methyl-2-oxo(thioxo)-1,2-dihydroquinoxalines 1a,b with alpha-D-glucopyranosyl, alpha-D-galactopyranosyl, and alpha-D-lactosyl bromide in the presence of K2CO3 followed by deacetylation with Et3N/H2O. Furthermore, alkylation of 1a,b with 4 bromobutyl acetate, 2-acetoxyethoxymethyl bromide, and 3-chloropropanol afforded the corresponding O- and S-acycloquinoxaline nucleosides. Reaction of 1b with chloroacetic acid followed by condensation with sulfacetamide and sulfadiazine in the presence of Et3N/THF and ethyl chloroformate gave the corresponding sulfonamide derivatives 14 and 15, respectively. The structures of new compounds were confirmed by using IR, (1)H, (13)C NMR spectra and microanalysis. Some of these compounds were screened in vitro for antitumor and antifungal activities. PMID- 26810145 TI - Enzymatic degradation of aromatic hydrocarbon intermediates using a recombinant dioxygenase immobilized onto surfactant-activated carbon nanotube. AB - This study examined the enzymatic decomposition of aromatic hydrocarbon intermediates (catechol, 4-chlorocatechol, and 3-methylcatechol) using a dioxygenase immobilized onto single-walled carbon nanotube (SWCNT). The surfaces of SWCNTs were activated with surfactants. The dioxygenase was obtained by recombinant technique: the corresponding gene was cloned from Arthrobacter chlorophenolicus A6, and the enzyme was overexpressed and purified subsequently. The enzyme immobilization yield was 62%, and the high level of enzyme activity was preserved (60-79%) after enzyme immobilization. Kinetic analyses showed that the substrate utilization rates and the catalytic efficiencies of the immobilized enzyme for all substrates (target aromatic hydrocarbon intermediates) tested were similar to those of the free enzyme, indicating that the loss of enzyme activity was minimal during enzyme immobilization. The immobilized enzyme was more stable than the free enzyme against abrupt changes in pH, temperature, and ionic strength. Moreover, it retained high enzyme activity even after repetitive use. PMID- 26810146 TI - Denitrifying sulfide removal process on high-tetracycline wastewater. AB - Antibiotics wastewater from tetracycline (TC) production unit can have high levels of chemical oxygen demand, ammonium and sulfate and up to a few hundreds of milligrams per liter of TC. Denitrifying sulfide removal (DSR) process is set up for simultaneously removal of sulfur, carbon and nitrogen from waters. The DSR process was for the first time studied for treating TC wastewaters. The TC stress has no adverse effects on removal rates of nitrate and acetate; however, it moderately deteriorated sulfide removal rates and S(0) accumulation rates when the concentration is higher than 100mgL(-1) TC. The Thauera sp., and Pseudomonas sp. present the heterotrophs and Sulfurovum sp. presented the autotroph for the present DSR reactions. The high tolerance of TC stress by the tested consortium was explained by the excess production of extracellular polymeric substances at high TC concentration, which can bind with TC for minimizing its inhibition effects. PMID- 26810147 TI - Impact of vaccination uptake on hospitalizations due to rotavirus acute gastroenteritis in 2 different socioeconomic areas of Spain. AB - Rotavirus is the leading cause of hospitalization due to acute gastroenteritis (AGE) in infants and toddlers. However, rotavirus vaccination has been associated with a decline in hospitalization rates due to rotavirus AGE. A descriptive retrospective study was conducted to analyze the impact of rotavirus vaccination on the rate of hospitalizations due to AGE among children <=2 years old in 2 areas of the province of Almeria, Spain. After eight years of rotavirus vaccination, rates of hospitalizations due to rotavirus AGE are diminished. This decline is closely related to vaccine coverage in the studied areas. PMID- 26810148 TI - Climate change-related regime shifts have altered spatial synchrony of plankton dynamics in the North Sea. AB - During the 1980s, the North Sea plankton community underwent a well-documented ecosystem regime shift, including both spatial changes (northward species range shifts) and temporal changes (increases in the total abundances of warmer water species). This regime shift has been attributed to climate change. Plankton provide a link between climate and higher trophic-level organisms, which can forage on large spatial and temporal scales. It is therefore important to understand not only whether climate change affects purely spatial or temporal aspects of plankton dynamics, but also whether it affects spatiotemporal aspects such as metapopulation synchrony. If plankton synchrony is altered, higher trophic-level feeding patterns may be modified. A second motivation for investigating changes in synchrony is that the possibility of such alterations has been examined for few organisms, in spite of the fact that synchrony is ubiquitous and of major importance in ecology. This study uses correlation coefficients and spectral analysis to investigate whether synchrony changed between the periods 1959-1980 and 1989-2010. Twenty-three plankton taxa, sea surface temperature (SST), and wind speed were examined. Results revealed that synchrony in SST and plankton was altered. Changes were idiosyncratic, and were not explained by changes in abundance. Changes in the synchrony of Calanus helgolandicus and Para-pseudocalanus spp appeared to be driven by changes in SST synchrony. This study is one of few to document alterations of synchrony and climate-change impacts on synchrony. We discuss why climate-change impacts on synchrony may well be more common and consequential than previously recognized. PMID- 26810151 TI - [About two cases of primitive necrotizing fasciitis of the chest wall]. AB - INTRODUCTION: Necrotizing fasciitis is a severe bacterial necrotic infection that affects the skin and soft tissues. OBSERVATION: We report a rare observation of necrotizing fasciitis located at the thoracic wall. The management requires an appropriate antibiotherapy preceding a large necrosectomy taking all the affected areas, thus preparing the underlying tissues for a possible skin graft. CONCLUSION: Through these two observations and a literature review, we describe the medical and surgical management of necrotizing fasciitis. PMID- 26810152 TI - Thirty Years After the National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Trial: A New Era for Stroke Therapy. PMID- 26810153 TI - Upholding Family-Centered Care in the Face of High-Consequence Pathogens- Thinking Inside the Room. PMID- 26810154 TI - Time-Lapse Evaluation of Interactions Between Biodegradable Mg Particles and Cells. AB - Mg-based implants have promising applications as biodegradable materials in medicine for orthopedic, dental, and cardiovascular therapies. During wear and degradation microdebris are released. Time-lapse multidimensional microscopy (MM) is proposed here as a suitable tool to follow, in fixed intervals over 24-h periods, the interaction between cells and particles. Results of MM show interactions of macrophages (J774) with the magnesium particles (MgPa) that led to modifications of cell size and morphology, a decrease in duplication rate, and cell damage. Corrosion products were progressively formed on the surface of the particles and turbulence was generated due to hydrogen development. Changes were more significant after treating MgPa with potassium fluoride. In order to complement MM observations, membrane damage as detected by a lactase dehydrogenase (LDH) assay and mitochondrial activity as detected by a WST-1 assay with macrophages and osteoblasts (MC3T3-E1) were compared. A more significant concentration-dependent effect was detected for macrophages exposed to MgPa than for osteoblasts. Accordingly, complementary data showed that viability and cell cycle seem to be more altered in macrophages. In addition, protein profiles and expression of proteins associated with the adhesion process changed in the presence of MgPa. These studies revealed that time-lapse MM is a helpful tool for monitoring changes of biodegradable materials and the biological surrounding in real time and in situ. This information is useful in studies related to biodegradable biomaterials. PMID- 26810155 TI - A new dammarane saponin and other triterpenoids from Siolmatra brasiliensis and evaluation of the antidiabetic activity of its extract. AB - Context Siolmatra brasiliensis (Cogn.) Baill (Cucurbitaceae) is a climbing plant widely used for the treatment of diabetes mellitus symptoms. Objective This work evaluates the antidiabetic activity of an extract of S. brasiliensis in streptozotocin-diabetic rats and promotes the phytochemical investigation to isolate the major compounds of the same extract. Materials and methods Male Wistar rats were divided into normal (N) and diabetic rats (DC) treated with water; diabetic rats treated with 3U insulin (DI) or with 250 (DSb250) or 500 mg/kg (DSb500) of hydroalcoholic extract of the stalks of S. brasiliensis, via oral gavage, for 21 days. Physiological and biochemical parameters classically altered in diabetes were monitored. The triterpenoids were isolated from the ethyl acetate fraction under silica gel column chromatography and Sephadex-LH20 methods and their structures were determined by NMR, HR-ESI-MS and DC analysis. Results When compared with DC, DSb250 rats showed a reduction in the hyperglycemia (DC: 26.46 +/- 0.69 versus DSb250: 19.67 +/- 1.06 mmol/L) and glycosuria (DC: 43.02 +/- 3.19 versus DSb250: 28.46 +/- 2.14 mmol/24 h) and increase in hepatic glycogen (DC: 14.44 +/- 1.26 versus DSb250: 22.08 +/- 4.26 mg/g). Three known cucurbitacins were isolated from a hydroalcoholic extract of S. brasiliensis, i.e., cayaponosides A1, B4, D, and a new dammarane saponin 3-O beta-d-gentiobiosyl-26-O-beta-d-glucopyranosyl-20-hydroxydammar-24-ene. The structures of these compounds were elucidated by spectral data analysis of the natural products and their acetyl derivatives. Discussion and conclusion The known cucurbitacins and/or the new identified saponin may be related with the antidiabetic activity of S. brasiliensis. PMID- 26810157 TI - Comparison of adiposity indices and cut-off values in the prediction of metabolic syndrome in postmenopausal women. AB - AIMS: To compare adiposity indices and to assess their various cut-off values for the prediction of metabolic syndrome (MetS) in postmenopausal women. METHODS: One hundred forty nine volunteers (67.17+/-6.12 years) underwent body composition assessment using DXA and had 5 anthropometric indices measured (Waist Circumference, WC; Waist-to-Height Ratio, WHtR; Body Mass Index, BMI; Body Adiposity Index, BAI; and Conicity Index). Blood pressure was assessed using an oscillometric device and fasting blood samples were collected. MetS was classified according NCEP-ATP III. Cut-off values to predict MetS were obtained using Receiver Operating Characteristic (ROC) curve analyses and odds ratios were also calculated. RESULTS: MetS prevalence was 29.5% and subjects who were classified with MetS showed worse cardiometabolic outcomes and higher anthropometric indices values (p<0.05). With the exception of total- and LDL cholesterol, all remaining variables were significantly correlated with at least one of the adiposity indices, with the strongest relationships observed for the indices reflecting central body fat. The cut-off values were 88cm, 0.57cm/cm, 26.85kg/m(2), 43.7%, 36.34%, and 1.24 units for WC, WHtR, BMI, DXA-derived body fat percentage, BAI, and conicity index, respectively. Significant greater risks for MetS were found for volunteers who had WHtR (odds=9.08; CI: 1.81-45.47) or WC (odds=5.20; CI: 1.30-20.73) measurements above cut-off values. CONCLUSION: Adiposity indices are associated with MetS in postmenopausal women in different degrees. Indices which consider central adiposity such as WC and WHtR have a stronger relationship with MetS compared to DXA-derived body fat percentage, which is considered a gold standard. PMID- 26810156 TI - Genome-wide association mapping revealed a diverse genetic basis of seed dormancy across subpopulations in rice (Oryza sativa L.). AB - BACKGROUND: Seed dormancy is an adaptive trait employed by flowering plants to avoid harsh environmental conditions for the continuity of their next generations. In cereal crops, moderate seed dormancy could help prevent pre harvest sprouting and improve grain yield and quality. We performed a genome wide association study (GWAS) for dormancy, based on seed germination percentage (GP) in freshly harvested seeds (FHS) and after-ripened seeds (ARS) in 350 worldwide accessions that were characterized with strong population structure of indica, japonica and Aus subpopulations. RESULTS: The germination tests revealed that Aus and indica rice had stronger seed dormancy than japonica rice in FHS. Association analysis revealed 16 loci significantly associated with GP in FHS and 38 in ARS. Three out of the 38 loci detected in ARS were also detected in FHS and 13 of the ARS loci were detected near previously mapped dormancy QTL. In FHS, three of the association loci were located within 100 kb around previously cloned GA/IAA inactivation genes such as GA2ox3, EUI1 and GH3-2 and one near dormancy gene, Sdr4. In ARS, an association signal was detected near ABA signaling gene ABI5. No association peaks were commonly detected among the sub-populations in FHS and only one association peak was detected in both indica and japonica populations in ARS. Sdr4 and GA2OX3 haplotype analysis showed that Aus and indica II (IndII) varieties had stronger dormancy alleles whereas indica I (IndI) and japonica had weak or non-dormancy alleles. CONCLUSION: The association study and haplotype analysis together, indicate an involvement of independent genes and alleles contributing towards regulation and natural variation of seed dormancy among the rice sub-populations. PMID- 26810158 TI - Association between serum uric acid (SUA) levels and metabolic syndrome (MetS) components in personnel of Shahroud University of Medical Sciences. AB - AIMS: Serum uric acid level has been suggested to be associated with metabolic syndrome risk factors. However, the association between metabolic syndrome and serum uric acid is still controversial and challenging. This study was aimed to investigate the association between serum uric acid levels and metabolic syndrome components in personnel of the Shahroud University of Medical Sciences. MATERIAL AND METHODS: This case-control study was conducted on 499 personnel aged 30-60 years old who were working in Shahroud University of Medical Sciences, in 2015. MetS was defined according to the National Cholesterol Education Program (NCEP) criteria. The relationship between serum UA level and the number of metabolic components was determined by linear regression analysis. RESULT: In this study, the mean concentration of serum uric acid in men with the syndrome was higher than that in women. Mean serum UA level increased as the number of metabolic factors increased. The mean serum uric acid levels was 4.98+/-1.64 in patients with metabolic syndrome and 4.5+/-1.28 in non-patients (p=0.005). Subject with abnormal uric acid were almost 2.62 times more likely than other subject to develop the syndrome. CONCLUSIONS: The results of this study showed that only hypertriglyceridemia is a component which increases the risk of hyperuricemia. In addition, hyperuricemia increases the risk of metabolic syndrome by more than two fold. It seems that high uric acid can be considered as a predisposing factor for metabolic syndrome; thus, it is recommended to measure serum uric acid in routine tests. PMID- 26810159 TI - Correlation between non-alcoholic fatty liver disease (NAFLD) and dyslipidemia in type 2 diabetes. AB - Non-alcoholic fatty liver means the presence of hepatosteatosis without significant alcohol consumption; it is strongly associated with obesity and metabolic disorder like type 2 diabetes and dyslipideamia. NASH may progress to advanced stages of hepatic fibrosis and cirrhosis. Increased body mass index and viral genotype contribute to steatosis in chronic hepatitis. The sonographic features of NAFLD include the presence of bright hepatic echotexture deep attenuation, and vascular blurring either singly or in combination. Dyslipidemia in patients with NAFLD is atherogenic in nature and it is characterized by increased levels of serum triglycerides and decreased levels of HDL cholesterol. Statins are potent lipid-lowering agents which decrease LDL cholesterol by 20 60%, decrease triglycerides by 10-33% and increase HDL cholesterol by 5-10% for the patients with NAFLD. PMID- 26810160 TI - Conversion of Cn-Unsaturated into Cn-2-Saturated LCFA Can Occur Uncoupled from Methanogenesis in Anaerobic Bioreactors. AB - Fat, oils, and grease present in complex wastewater can be readily converted to methane, but the energy potential of these compounds is not always recyclable, due to incomplete degradation of long chain fatty acids (LCFA) released during lipids hydrolysis. Oleate (C18:1) is generally the dominant LCFA in lipid containing wastewater, and its conversion in anaerobic bioreactors results in palmitate (C16:0) accumulation. The reason why oleate is continuously converted to palmitate without further degradation via beta-oxidation is still unknown. In this work, the influence of methanogenic activity in the initial conversion steps of unsaturated LCFA was studied in 10 bioreactors continuously operated with saturated or unsaturated C16- and C18-LCFA, in the presence or absence of the methanogenic inhibitor bromoethanesulfonate (BrES). Saturated Cn-2-LCFA accumulated both in the presence and absence of BrES during the degradation of unsaturated Cn-LCFA, and represented more than 50% of total LCFA. In the presence of BrES further conversion of saturated intermediates did not proceed, not even when prolonged batch incubation was applied. As the initial steps of unsaturated LCFA degradation proceed uncoupled from methanogenesis, accumulation of saturated LCFA can be expected. Analysis of the active microbial communities suggests a role for facultative anaerobic bacteria in the initial steps of unsaturated LCFA biodegradation. Understanding this role is now imperative to optimize methane production from LCFA. PMID- 26810162 TI - Risk of tuberculosis in patients treated with biological medicines. AB - OBJECTIVE: The number of medicines used for biological therapy is constantly increasing. Biologic medicines selectively block the immunological processes leading to autoimmune manifestations with tissue damage or block the progression of haemato-oncological or other malignancies. Biological medicines are usually monoclonal antibodies or inhibitors of certain cytokines, cell receptors and enzymes. Their administration results in immunosuppression associated with increased risk of infectious complications, including tuberculosis. Assessment of the risk of tuberculosis associated with biological medicines is an important part of the medical decision done by pneumologist. We describe the risks of different biologicals and suggest the possible necessary steps in evaluating the risk of tuberculosis in individual patient (Ref. 18). PMID- 26810161 TI - Characterization of surgical cardiac tumors. AB - OBJECTIVE: The primary tumors of the heart are extremely rare. There are divided to benign, malignant and metastatic. Metastatic cardiac tumors are more common. METHODS: The incidence in contemporary echocardiographic series is reported at a higher frequency of 0.15%. 75% of cardiac tumors are benign; approximately half of these are cardiac mommas. The malignant cardiac tumors are mostly histopathologically undifferentiated, followed by leiomyosarcomas and angio sarcomas. RESULTS: Cardiac tumors have a wide range of unique clinical presentation. Even the most benign and smallest tumor can lead to significant morbidity and mortality. The clinical presentations of the primary cardiac tumors are due to: blood flow obstruction, tumor embolization and constitutional symptoms. Clinical presentations can be varied and may resemble coronary disease, pericarditis, cardiomyopathy or valve malfunction. The recent technological advances in non-invasive imaging modalities such as echocardiography and cardiac magnetic resonance imaging is rapidly increases the early diagnosis and management approach. CONCLUSION: In this review we aim to summarize the characterization of the most common cardiac tumors. Early recognition and treatment provided the best results (Tab. 2, Fig. 6, Ref. 66). PMID- 26810163 TI - Soluble receptor for advanced glycation end products in late-onset neonatal infection. AB - OBJECTIVES: To assess the plasma levels of sRAGE (soluble receptor for advanced glycation end products) in infected and non-infected preterm neonates and to compare their diagnostic values with standard infection biomarkers. BACKGROUND: RAGE activates pathways responsible for acute and chronic inflammation. The soluble type of this receptor, sRAGE, which acts as a decoy receptor, has been linked to the severity of sepsis and its outcome. METHODS: Prospective clinical study was carried out from January 2011 to August 2013. There were 33 neonates included according to their infection status and divided into subgroups as follows: infected (I), septic (S), non-infected controls (C). RESULTS: We found significantly lower values of sRAGE in the subgroup S (905.54+/-220.53 pg/mL; p < 0.028), while borderline values were higher in the subgroup I vs C (2158.33+/ 197.33 pg/mL vs 1744.80+/-157.74 pg/mL; p < 0.064). By analysing the interobserver concordance we detected 70 % agreement as to sRAGE values detected in neonatal late-onset infections and sepsis, while procalcitonin was used as golden standard. CONCLUSION: Plasma sRAGE values reflect the severity of the inflammatory status in late-onset infection and sepsis in preterm neonates. Our results indicate that sRAGE could be a good potential biomarker of late-onset neonatal infection and sepsis (Tab. 2, Ref. 14). PMID- 26810164 TI - Validation study of a conventional enzyme immunoassay to detect HIV antibodies in oral fluid. AB - OBJECTIVES: The aim of our study was to validate the Genscreen HIV 1/2 version 2 (BIO-RAD) for detecting HIV antibodies in oral fluid specimens (OF). BACKGROUND: The advantage of assays to detect HIV infection in OF lies in the on-site easy access and noninvasive sample collection. METHODS: Paired serum and OF were collected from 496 subjects (263 HIV-positive and 233 HIV-negative) using the Oracol test kit (Oracle Diagnostics, Inc). The quality of OF was verified by measuring total IgGs using the Human IgG ELISA Quantitation Kit (Bethyl Lab.inc). All reactive OF samples were retested by Western blot HIV1/2 BLOT 2.2 (MP Biomedical, Singapore, China). RESULTS: Of 263 OF samples from participants with blood-based HIV-positive results, 259 were positive by Genscreen HIV 1/2 version 2 (98.48% sensitivity, 95% CI; 96.2-99.6). The 233 individuals who had a non reactive HIV blood test were found negative on testing their OF by Genscreen HIV 1/2 version 2 (100% specificity, 95% CI; 98.4-100). NPV and PPV of the assay were 98.31% (95% CI; 95.74-99.34) and 100%, (95% CI; 98.53-100.00), respectively. CONCLUSION: Genscreen HIV 1/2 version 2 (Bio-Rad) is a prospective method for HIV surveillance studies in hard-to-reach populations with high risk behavior using non-invasive OF collection (Tab. 1, Fig. 1, Ref. 16). PMID- 26810165 TI - Type and occurrence of serious complications in patients after mild traumatic brain injury. AB - Traumatic brain injury (TBI) remains a major public health and socio-economic problem, and 70-90% of all TBIs are classified as mild. Mild TBIs and concussions are mostly considered to be non-serious conditions with symptoms subsiding within a few days or weeks. However in 10-15% of patients, the symptoms persist one year after concussion and mostly include headache, fatigue, irritability, and cognitive problems (e.g. memory, concentration). These persisting symptoms negatively influence patient daily activities as postconcussion syndrome (PCS). Second-impact syndrome (SIS) is a very rare but usually fatal condition and occurs when repeated brain injuries lead to a catastrophic diffuse brain swelling. There is no scientific evidence on the incidence and risk of SIS. Chronic traumatic encephalopathy (CTE) is a progressive degenerative disease of the brain found in patients with a history of repetitive brain trauma. CTE presents with behavioural, cognitive, and motor symptoms. The literature to date lacks prospective epidemiological studies of the incidence of CTE. In recent medical literature, there is a description of 110 athletes with postmortem diagnosis of CTE (Tab. 1, Ref. 37). PMID- 26810166 TI - Some aspects of health status of the Gypsy population in Slovakia. AB - Population of the Gypsy people living currently in Slovakia reaches approximately 400,000 people which represents 7.5% of the total Slovak population. The age structure of the Gypsy population is of a considerably progressive type with a high number of children and very low number of old people. This is due to the high natality and high mortality of Gypsies, whose health status is worse than the health status of the majority population. Gypsy people represent an important "old-new" risk group in case of tuberculosis and a more frequent occurrence of other transmitted diseases is observed in them while a higher incidence of genetically conditioned diseases has been confirmed, as well. As for children, a higher frequency of infectious diseases, injuries, intoxications and burns can be found as a result of their environmental conditions. A high level of infant mortality of the Gypsy children is a very negative phenomenon. We can state that the lifestyle of the Gypsy population is unhealthy, characterized by bad dietary habits, drinking alcohol, frequent smoking already in a very young age, higher weight and lower physical activity. All findings confirm that the Gypsy population is threatened by cardiovascular diseases at younger age already. Due to a more difficult approach to the health care, part of the Gypsies consult the physician only when in a serious health state. Health status of the Gypsy seniors has been reported only at minimum due to their low representation in population. Typical feature of this ethnic is, that they take care of their seniors. To prove this, during the author's twenty seven-year practice he met just three old Gypsy women in social institutions. It is very difficult to address problems related to the Gypsy population; this task requires engagement of all spheres of our society, in particular of the Gypsies themselves, including their organizations (Ref. 50). PMID- 26810167 TI - Antibacterial effects of conventional glass ionomer cement. AB - OBJECTIVES: The antibacterial activity of conventional glass ionomer cement against three different microorganism strains alone and following incorporation of 1, 2 and 3% Benzalkonium Chloride and Cetylpyridinium Chloride was evaluated. METHODS: Agar diffusion method was used to determine the inhibitory effect of the conventional glass ionomer cement ChemFlex on Streptococcus mutans, Lactobacillus casei and Actinomyces viscosus. Bacterial strains were inoculated into BHIB, and incubated in an anaerobic atmosphere (37 degrees C). From the bacteria grown in the liquid medium, the density of the inoculum was set to be equivalent to McFarland 2 standard. In Shaedler agar, 350 MUL of the bacterial suspension were equally spread. Specimens (4 mm * 6 mm) were prepared from the cement without and with addition of 1, 2 and 3% Benzalkonium Chloride and Cetylpyridinium Chloride. The inhibition zones were determined after 48 hours, after 2, 7 and 21 days of incubation. RESULTS: The combination ChemFlex + Benzalkonium Chloride has the best effect on the three analysed bacteria. The Benzalkonium Chloride antibacterial compound has a stronger antibacterial effect than Cetylpyridinium Chloride. CONCLUSIONS: Glass ionomer cements can potentially be used as a medium for slow release of active antimicrobial components, and they have the potential to improve clinical outcomes of the cements (Tab. 3, Fig. 3, Ref. 31). PMID- 26810168 TI - Vitamin C ameliorates high dose Dexmedetomidine induced liver injury. AB - BACKGROUND: We investigated whether vitamin C has protective effects on rat liver tissue treated with different dexmedetomidine doses. MATERIAL AND METHODS: Thirty five wistar albino rats were randomly divided into 5 groups (Control (0.9% NaCl intraperitoneally (i.p.), Dexmedetomidine 5 MUg.kg(-1) (i.p.), Dexmedetomidine 5 MUg.kg(-1) i.p. plus Vitamin C (100 mg.kg(-1)), Dexmedetomidine 10 MUg.kg(-1) i.p. and Dexmedetomidine 10 MUg.kg(-1) i.p. plus Vitamin C (100 mg.kg(-1)). Histopathological liver injury, superoxide dismutase (SOD) activity and tissue Malondialdehyde levels were investigated. RESULTS: Hepatocyte degeneration was significantly higher in D10 group than those in other study groups (p < 0.0001, p = 0.002, p < 0.0001, p = 0.005, respectively). Similarly, liver tissue sinusoidal dilatation and hepatocyte necrosis were significantly higher in D10 group than those in other groups (p < 0.0001, p < 0.0001, p = 0.002, p < 0.0001 and p < 0.0001, p = 0.046, p < 0.0001 and p = 0.002, respectively). Tissue MDA levels in D10 group were significantly higher than those in control, D5+Vit C and D10+Vit C groups (p = 0.028, p = 0.004, p = 0.031, respectively). SOD enzyme activity in D10 group was significantly lower than in control, D5+Vit C and D10+Vit C groups (p < 0.0001, p = 0.023 and p = 0.031, respectively). CONCLUSION: High dose dexmedetomidine can induce hepatic injury and oxidative stress in rats while pre treatment with vitamin C may be effective in protecting liver tissue against this newly recognized undesirable dexmedetomidine effect (Tab. 2, Fig. 5, Ref. 30). PMID- 26810169 TI - The effects of epidural bupivacaine on ischemia/reperfusion-induced liver injury. AB - BACKGROUND: Several animal studies showed beneficial effects of thoracic epidural anesthesia (TEA) in hippocampal, mesenteric and myocardial IR injury (2-4). In this study, we investigated the effects of epidural bupivacaine on hepatic ischemia reperfusion injury in a rat model. MATERIAL AND METHODS: Eighteen rats were randomly divided into three groups each containing 6 animals. The rats in Group C had sham laparotomy. The rats in the Group S were subjected to liver IR through laparotomy and 20 mcg/kg/h 0.9% NaCl was administered to these rats via an epidural catheter. The rats in the Group B were subjected to liver IR and were given 20 mcg/kg/h bupivacaine via an epidural catheter. Liver tissue was harvested for MDA analysis, apoptosis and histopathological examination after 60 minutes of ischemia followed by 360 minutes of reperfusion. Blood samples were also collected for TNF-alpha, IL-1beta, AST and ALT analysis. RESULTS: The AST and ALT levels were higher in ischemia and reperfusion group, which received only normal saline via the thoracic epidural catheter, compared to the sham group. In the ischemia reperfusion group, which received bupivacaine via the epidural catheter, IL-1 levels were significantly higher than in the other groups. TNF alpha levels were higher in the Groups S and B compared to the sham group. Bupivacaine administration induced apoptosis in all animals. CONCLUSION: These results showed that thoracic epidural bupivacaine was not a suitable agent for preventing inflammatory response and lipid peroxidation in experimental hepatic IR injury in rats. Moreover, epidural bupivacaine triggered apoptosis in hepatocytes. Further research is needed as there are no studies in literature investigate the effects of epidural bupivacaine on hepatic ischemia reperfusion injury (Tab. 3, Fig. 3, Ref. 34). PMID- 26810170 TI - Combination effect of melatonin and dexamethasone on liver ischemia/reperfusion injury. AB - OBJECTIVE: Liver failure following ischemia-reperfusion (I/R) injury is a major concern in liver surgery. The purpose of this study was to evaluate combination pretreatment with melatonin (MEL) and dexamethasone (DEX) on liver I/R model. Male Wistar rats (n = 60) were assigned to 5 groups of 12 animals each: (1) Sham: laparotomy without I/R; (2) I/R: hepatic I/R; (3) I/R+MEL: hepatic I/R+melatonin injected intraperitoneally (20 mg/kg); (4) I/R+DEX: hepatic I/R+ dexamethasone injected intravenously (10 mg/kg); (5) I/R+MEL+DEX: hepatic I/R+ melatonin injected intraperitoneally+dexamethasone injected intravenously. The liver was subjected to ischemia by clamping the portal triad for 30 minutes and then reperfused for 6 hours after ischemia by removing the clamps. RESULTS: The levels of glutathione peroxidase (GPx) and superoxide dismutase (SOD) decreased after hepatic I/R in all groups. Levels of GPx and SOD were higher in I/R+MEL+DEX group compared to I/R, I/R+MEL and I/R+DEX groups and they were significantly higher in I/R+MEL group compared to I/R and I/R+DEX groups (p < 0.05). Levels of ALT, AST, TNF-alpha, hepatic tissue malondialdehyde (MDA), liver injury index, and apoptotic index increased after hepatic I/R. Levels of ALT, AST, tissue MDA, tissue injury index and apoptotic index were lower in I/R+MEL+DEX group compared to those in I/R, I/R+MEL and I/R+DEX groups, and in I/R+MEL they were significantly lower than in I/R+DEX group (p < 0.05). TNF-alpha level was lower in I/R+MEL+DEX group compared to other groups and it was significantly lower in I/R+DEX group than in I/R+MEL and I/R groups (p < 0.05). CONCLUSION: Combination therapy with melatonin and dexamethasone had better results in decreasing the liver injury compared to when each of them was administered alone (Tab. 3, Ref. 58). PMID- 26810171 TI - Polylactic acid and polyethylene glycol prevent surgical adhesions. AB - OBJECTIVES: Re-mediastinoscopy could be risky because of adhesions from the previous mediastinoscopy. The aim of this study was to evaluate the efficacy of a bio-resorbable barrier on adhesion formation in a re-mediastinoscopy rat model. METHODS: Mediastinal dissection similar to mediastinoscopy was done in twenty eight rats and a polymeric film comprising of polylactic acid and polyethylene glycol (Repel-cv(r), SyntheMed Inc., NJ, USA) was placed on trachea in the study groups. Group 1 (sham, sacrificed at day 30), Group 2 (single barrier, sacrificed at day 30), Group 3 (single barrier, sacrificed at day 60), Group 4(double layer barrier, sacrificed at day 60). Mediastinal adhesions, degree of inflammation, vascular proliferation, foreign body reaction and fibroblast proliferation was compared. RESULTS: Macroscopic dissection showed significantly dense adhesions in Sham Group and Group 3 (p < 0.05). Histopathologic examination showed that there was a significant difference between groups when the foreign body reaction and fibroblast proliferation was evaluated (p0.05). CONCLUSIONS: This unique experimental study showed that adhesion barrier was effective as single layer application at day 30 and double layer application at day 60. At clinical conversion, by the application of barrier, the formation of adhesions might be decreased to provide a safe re-mediastinoscopy (Tab. 2, Fig. 4, Ref. 23). PMID- 26810172 TI - Gastric cancer with liver metastasis. AB - Surgical treatment of gastric cancer with liver metastasis (GCLM) is currently a frequent topic of discussion at professional surgical symposia. There is a low number of patients and a lack of large clinical multi-center studies describing the benefits of this treatment approach. The article describes a patient with GCLM, growing through stomach wall serosa, invading the spleen hilum, distal part of pancreas with metastasis to S7 of the right liver lobe. The patient had total gastrectomy performed with D2 lymphadenectomy, distal pancreatectomy with splenectomy, resection of diaphragm and RFA of the metastatic lesion in S7 of the liver. Post-surgery course was free of complications, followed by adjuvant chemotherapy. 2 years after the surgery, the patient is in full remission, free of any relapse. Liver resection or RFA is not commonly used in the gastric cancer with liver metastasis (GCLM). At present, there is no direct marker available to define the degree of biological aggressiveness of the tumor (indicating or contra indicating the surgical treatment), therefore we are left to rely on indirect prognostic factors: cancer invasion in the gastric wall serosa, presence of 3 and more liver metastases, size of metastasis exceeding 50 mm (Fig. 2, Ref. 13). PMID- 26810173 TI - Life with an unwelcome guest - caring in a context of protracted bodily pain. AB - Protracted bodily pain is a phenomenon that often affects a human being's whole life. Care of human beings with protracted pain is challenging because pain is not always measureable, and the experiences of pain are subjective, unique and shapeshifting. Therefore, the aim is to highlight what protracted bodily pain signifies for the human being, and human beings' experiences of what is caring in a context of protracted bodily pain. Four informants with protracted bodily pain took part in a focus group interview. The interview was analysed by using a qualitative content analysis with a hermeneutic approach. The findings show that protracted pain renders human beings speechless, limits and robs them of their lives. The pain is described as a domineering, unpleasant and unwelcome guest. The pain can change the human being's personality and creates feelings of guilt. Uncertainty about the origin of the pain as well as a nonchalant treatment or not being believed intensifies the pain. Human being experience mastering the pain, encounters with caregivers who can ease the burden, community with others and finding that little something extra in everyday life is experienced as caring. From a caring science perspective, the relation between protracted pain and suffering is obvious. Suffering emerges as illness suffering, as life suffering and as suffering caused by care. Professional as well as natural caring is important in a context of protracted bodily pain. The human being longs to encounter caregivers who are courageous enough to lay themselves on the line. Community with people who are prepared to share the burden eases the heavy burden that pain brings to life, it brings hope and relief. PMID- 26810177 TI - Immediate and Delayed Hypersensitivity Reactions to Proton Pump Inhibitors: Evaluation and Management. AB - PPIs are among the most commonly administered medications in the USA and are generally well tolerated. Immediate and delayed immune-mediated hypersensitivity reactions are rare but increasingly recognized adverse effects of proton pump inhibitors (PPIs). Immediate hypersensitivity reactions can occur due to IgE mediated hypersensitivity to PPIs and can be evaluated by immediate hypersensitivity skin testing and oral provocation challenge testing. A desensitization protocol can be used when PPI use cannot be avoided in an allergic patient. Delayed hypersensitivity reactions to PPIs have also been reported. Occupational exposures causing cutaneous reactions to PPIs are the most commonly reported delayed hypersensitivity reaction, followed by drug-induced subacute cutaneous lupus erythematosus. This review presents a summary of the clinical presentation, diagnostic evaluation, and management of immune-mediated hypersensitivity reactions to PPIs. PMID- 26810178 TI - Transcriptional response to heat shock in liver of snow trout (Schizothorax richardsonii)--a vulnerable Himalayan Cyprinid fish. AB - The snow trout (Schizothorax richardsonii) belonging to family Cyprinidae, is an endemic fish of the Himalayan region. The species is tagged as vulnerable species in the IUCN red list of threatened species. The fish thrives well in snowmelt water of several streams and rivers in the region but are occasionally exposed to more than 20 degrees C during the summer season. Therefore, we have used deep RNA sequencing to decipher the transcriptome of snow trout and characterize the genes and molecular pathways involved in heat shock response. In this study 72,601,298 and 65,428,283 raw reads for heat-shocked and control, respectively, were obtained by Illumina paired-end sequencing technology. The de novo assembled transcriptome was tested for differential gene expression across the treatment groups. The quality of assembly was high with N75 and N50 lengths of 461 and 1274 bases, respectively. A total of 65 unique transcripts were differentially expressed in liver under heat shock and control. Annotated blast matches reveal that differentially expressed transcripts correspond to critical chaperones and molecular pathways, previously shown to be important for thermal stress in other fish species. Eight randomly selected heat-stressed responsive transcripts were also observed to be upregulated during qRT-PCR analysis. This study is the preliminary step to understanding the responses during sudden environmental changes like heat shock. The reference transcriptome database would also aid further studies on biological and physiological aspects of the snow trout under abiotic stresses. PMID- 26810180 TI - The relevance of memory sensitivity for psychological well-being in aging. AB - PURPOSE: In the present study, we investigated the relationship between memory sensitivity, which describes a positive attitude to autobiographical memory and the presence of behaviors devoted to saving memories of the personal past, and psychological well-being; in particular, we tested whether their relationship would change across age groups. METHODS: Three hundred eighteen participants, divided in four groups: young to middle-aged adults (20-55 years old), young-old adults (65-74 years old), old adults (75-84 years old), and old-old adults (85-97 years old), completed questionnaires on their memory sensitivity and psychological well-being. RESULTS: Memory sensitivity slightly decreased with age and had a positive relationship with psychological well-being that was critically moderated by age. Specifically, the relationship between memory sensitivity and psychological well-being became increasingly stronger as age increased. CONCLUSIONS: While memory sensitivity may have little or no particular relevance in the case of young to middle-aged adults, it has an increasingly important positive relationship with psychological well-being at later age. It is thus suggested that memory sensitivity represents a dimension that should be considered in the study and interventions on quality of life in the elderly population. PMID- 26810181 TI - Automatic Gain Control in Compact Spectrometers. AB - An image intensifier installed in the optical path of a compact spectrometer may act not only as a fast gating unit, which is widely used for time-resolved measurements, but also as a variable attenuator-amplifier in a continuous wave mode. This opens the possibility of an automatic gain control, a new feature in spectroscopy. With it, the user is relieved from the necessity to manually adjust signal level at a certain value that it is done automatically by means of an electronic feedback loop. It is even more important that automatic gain control is done without changing exposure time, which is an additional benefit in time resolved experiments. The concept, algorithm, design considerations, and experimental results are presented. PMID- 26810179 TI - In silico analysis of regulatory and structural motifs of the ovine HSP90AA1 gene. AB - Gene promoters are essential regions of DNA where the transcriptional molecular machinery to produce RNA molecules is recruited. In this process, DNA epigenetic modifications can acquire a fundamental role in the regulation of gene expression. Recently, in a previous work of our group, functional features and DNA methylation involved in the ovine HSP90AA1 gene expression regulation have been observed. In this work, we report a combination of methylation analysis by bisulfite sequencing in several tissues and at different developmental stages together with in silico bioinformatic analysis of putative regulating factors in order to identify regulative mechanisms both at the promoter and gene body. Our results show a "hybrid structure" (TATA box + CpG island) of the ovine HSP90AA1 gene promoter both in somatic and non-differentiated germ tissues, revealing the ability of the HSP90AA1 gene to be regulated both in an inducible and constitutive fashion. In addition, in silico analysis showed that several putative alternative spliced regulatory motifs, exonic splicing enhancers (ESEs), and G-quadruplex secondary structures were somehow related to the DNA methylation pattern found. The results obtained here could help explain the differences in cell-type transcripts, tissue expression rate, and transcription silencing mechanisms found in this gene. PMID- 26810182 TI - Study of Spectral Modifications in Acidified Ignitable Liquids by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy. AB - In this work, the spectral characteristics of two types of acidified gasoline and acidified diesel fuel are discussed. Neat and acidified ignitable liquids (ILs) infrared absorption spectra obtained by attenuated total reflection Fourier transform infrared spectroscopy were compared in order to identify the modifications produced by the reaction of the ILs with sulfuric acid. Several bands crucial for gasoline identification were modified, and new bands appeared over the reaction time. In the case of acidified diesel fuel, no significant modifications were observed. Additionally, the neat and acidified ILs spectra were used to perform a principal components analysis in order to confirm objectively the results. The complete discrimination among samples was successfully achieved, including the complete differentiation among gasoline types. Taking into account the results obtained in this work, it is possible to propose spectral fingerprints for the identification of non-burned acidified ILs in forensic investigations related with arson or the use of improvised incendiary devices (IIDs). PMID- 26810183 TI - In-line Monitoring of Monomer and Polymer Content During Microgel Synthesis Using Precipitation Polymerization via Raman Spectroscopy and Indirect Hard Modeling. AB - This contribution presents in-line monitoring of microgel synthesis by precipitation polymerization based on Raman spectroscopy. The spectra are evaluated via multivariate Indirect Hard Modeling (IHM) regression. Therefore, mechanistic models of the pure component spectra for solvent, monomer, and microgel are created by a sum of adaptable parameterized peak functions (Gaussian Lorentzian). Instead of individual calibrations for each analyte, one comprehensive model is calibrated to predict both the monomer and microgel fraction while ensuring a consistent mass balance. As a novelty, this leads to an in-line microgel quantification based on an interactive spectral model. The results show cross-validation errors (RMSECV) of monomer and microgel fractions as low as 0.028 wt % and 0.084 wt %, respectively. The ability of IHM to account for non-linear spectral changes was found to reduce the microgel RMSECV by a factor of two compared to linear CLS regression. The calibration model allows simultaneous observation of the decrease in monomer content and the formation of microgels. Long as well as short focus immersion optics reveal characteristic vibrations of the turbid microgel suspension, although long focus optics are influenced by scattering particles to a greater extent. Precise examination of the model proves that the prediction is robust against changes in microgel particle size or temperature, which opens up the application of Raman spectroscopy as a comprehensive process analytical technology in microgel synthesis. PMID- 26810184 TI - A Comparative Study of Single-pulse and Double-pulse Laser-Induced Breakdown Spectroscopy with Uranium-containing Samples. AB - Laser-induced breakdown spectroscopy (LIBS) holds potential advantages in special nuclear material (SNM) sensing and nuclear forensics, which require rapid analysis, minimal sample preparation, and stand-off distance capability. SNM, such as U, however, result in crowded emission spectra with LIBS, and characteristic emission lines are challenging to discern. It is well-known that double-pulse LIBS (DPLIBS) improves the signal intensity for analytes over conventional single-pulse LIBS (SPLIBS). This study investigates the U signal in a glass matrix using DPLIBS and compares it to signal obtained using SPLIBS. Double-pulse LIBS involves sequential firing of a 1.06 um Nd:YAG pre-pulse and 10.6 um TEA CO2 heating pulse in a near collinear geometry. Optimization of experimental parameters including inter-pulse delay and energy follows identification of characteristic lines for the bulk analyte Ca and the minor constituent analyte U for both DPLIBS and SPLIBS. Spatial and temporal coupling of the two pulses in the proposed DPLIBS technique yields improvements in analytical merits with a negligible increase in damage to the sample compared to SPLIBS. Subsequently, the study discusses optimum plasma emission conditions of U lines and relative figures of merit in both SPLIBS and DPLIBS. Investigation into plasma characteristics also addresses plausible mechanisms related to the observed U analyte signal variation between SPLIBS and DPLIBS. PMID- 26810185 TI - Application of the Polynomial-Based Least Squares and Total Least Squares Models for the Attenuated Total Reflection Fourier Transform Infrared Spectra of Binary Mixtures of Hydroxyl Compounds. AB - An analysis of binary mixtures of hydroxyl compound by Attenuated Total Reflection Fourier transform infrared spectroscopy (ATR FT-IR) and classical least squares (CLS) yield large model error due to the presence of unmodeled components such as H-bonded components. To accommodate these spectral variations, polynomial-based least squares (LSP) and polynomial-based total least squares (TLSP) are proposed to capture the nonlinear absorbance-concentration relationship. LSP is based on assuming that only absorbance noise exists; while TLSP takes both absorbance noise and concentration noise into consideration. In addition, based on different solving strategy, two optimization algorithms (limited-memory Broyden-Fletcher-Goldfarb-Shanno (LBFGS) algorithm and Levenberg Marquardt (LM) algorithm) are combined with TLSP and then two different TLSP versions (termed as TLSP-LBFGS and TLSP-LM) are formed. The optimum order of each nonlinear model is determined by cross-validation. Comparison and analyses of the four models are made from two aspects: absorbance prediction and concentration prediction. The results for water-ethanol solution and ethanol-ethyl lactate solution show that LSP, TLSP-LBFGS, and TLSP-LM can, for both absorbance prediction and concentration prediction, obtain smaller root mean square error of prediction than CLS. Additionally, they can also greatly enhance the accuracy of estimated pure component spectra. However, from the view of concentration prediction, the Wilcoxon signed rank test shows that there is no statistically significant difference between each nonlinear model and CLS. PMID- 26810186 TI - Genetic variations in interleukin-6 polymorphism and the association with susceptibility and overall survival of osteosarcoma. AB - Interleukin-6 (IL-6), a central proinflammatory cytokine, may be involved in both development and progression of many human malignancies. Therefore, we aimed to evaluate any associations of IL-6 gene polymorphisms with susceptibility and overall survival of osteosarcoma in a Chinese population. A total of 412 subjects, including 206 patients with osteosarcoma and 206 healthy controls, were recruited and were assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in this study. Significant differences of genotype distribution were observed between osteosarcoma cases and controls at the IL-6 174 G/C genotypes. Compared with the homozygote GG, the heterozygous GC genotype was associated with significantly increased risk for osteosarcoma (odds ratio [OR] = 1.58, 95 % confidence interval [CI] = 1.13-3.05, p = 0.028); the CC genotype was associated with increased risk for osteosarcoma (OR = 1.57, 95 % CI = 1.21-3.26, p = 0.022). Moreover, the genotype CC of IL-6 -174 G/C carried a higher risk of osteosarcoma metastasis and later Enneking stages, compared with the GG genotype. The IL-6 -174 G/C genotype was associated with risk for development and metastasis of osteosarcoma in Chinese Han population. PMID- 26810187 TI - Cyclin E amplification, over-expression, and relapse-free survival in HER-2 positive primary breast cancer. AB - Cyclin E is a well-characterized cell cycle regulator and an amplified oncogene in breast cancer. Over-expression of cyclin E has generally been associated with poor survival. Recent studies have shown an interaction between HER-2 (ERBB2) and cyclin E, but the exact mechanism is unknown. Interestingly, cyclin E over expression has been associated with trastuzumab resistance. We studied cyclin E over-expression, CCNE1 amplification, and relapse-free survival in HER-2-positive primary breast cancers treated with and without trastuzumab therapy. Formalin fixed paraffin-embedded tissue samples from 202 HER-2-positive breast carcinomas were studied. Expression levels of cyclin E and proliferation marker Ki-67 were determined using immunohistochemistry. Chromogenic in situ hybridization (CISH) with a gene-specific bacterial artificial chromosome (BAC) probe was used to analyze presence of CCNE1 amplification. Majority of HER-2-positive breast carcinomas exhibited nuclear staining for cyclin E protein. Cyclin E was highly expressed (>=50 % cells) in 37 % of cases. Incidence of CCNE1 amplification (>=6 gene copies/cell or clusters) was 8 %. Cyclin E amplification and over-expression were strongly associated with each other, grade, hormone receptors, and Ki-67. Neither high cyclin E expression nor CCNE1 amplification was associated with relapse-free survival (RFS) irrespective of short-term (9-week regimen) adjuvant trastuzumab therapy. These results confirm cyclin E and HER-2 gene co amplification in a fraction of HER-2-positive breast cancers. Cyclin E is frequently over-expressed but appears to have limited value as a prognostic or predictive factor in HER-2-positive breast cancer regardless of trastuzumab therapy. PMID- 26810188 TI - Combined niclosamide with cisplatin inhibits epithelial-mesenchymal transition and tumor growth in cisplatin-resistant triple-negative breast cancer. AB - Women with triple-negative breast cancer have worse prognosis compared to other breast cancer subtypes. Acquired drug resistance remains to be an important reason influencing triple-negative breast cancer treatment efficacy. A prevailing theory postulates that the cancer resistance and recurrence results from a subpopulation of tumor cells with stemness program, which are often insensitive to cytotoxic drugs such as cisplatin. Recent studies suggested that niclosamide, an anti-helminthic drug, has potential therapeutic activities against breast cancer stem cells, which prompts us to determine its roles on eliminating cisplatin-resistant cancer cells. Hence, we established a stable cisplatin resistant MDA-MB-231 cell line (231-CR) through continuously exposure to increasing concentrations of cisplatin (5-20 MUmol/l). Interestingly, 231-CR exhibited properties associated to epithelial-mesenchymal transition with enhanced invasion, preserved proliferation, increased mammosphere formation, and reduced apoptosis compared to naive MDA-MB-231 sensitive cells (231-CS). Importantly, niclosamide or combination with cisplatin inhibited both 231-CS and 231-CR cell proliferation in vitro. In addition, niclosamide reversed the EMT phenotype of 231-CR by downregulation of snail and vimentin. Mechanistically, niclosamide treatment in combination with or without cisplatin significantly inhibited Akt, ERK, and Src signaling pathways. In vivo study showed that niclosamide or combination with cisplatin could repress the growth of xenografts originated from either 231-CS or 231-CR cells, with prominent suppression of Ki67 expression. These findings suggested that niclosamide might serve as a novel therapeutic strategy, either alone or in combination with cisplatin, for triple negative breast cancer treatment, especially those resistant to cisplatin. PMID- 26810189 TI - Raddeanoside R13 inhibits breast cancer cell proliferation, invasion, and metastasis. AB - Pulsatilla chinensis is one of the 50 famous fundamental herbs used in traditional Chinese medicine. Saponins are the main components of P. chinensis. Although the anti-proliferative function of saponins has been established in plenty types of cancer, the role of saponins on tumor invasion and metastasis has not been reported, and the mechanisms of how saponins exert the anti-tumor functions are still poorly characterized. Here, we demonstrate that, in breast cancer (BC) cells, raddeanoside R13, a component of saponins extracted from P. chinensis, exhibits strong anti-proliferative and anti-metastasis ability, accompanied by cell cycle arrest, apoptosis, autophagy, and reversion of epithelial-mesenchymal transition (EMT). Raddeanoside R13 (R13) inhibits BC cell proliferation via the activation of G1/S checkpoint transitions, concomitant with a marked decrease of the positive cell cycle regulators, including cyclin D1, cyclin A, and cyclin B1. R13 induces BC cell apoptosis accompanied by the increased levels of cleaved PARP and caspase-3. R13 inhibits BC cell migration and invasion and regulates the expression of the markers of EMT, which plays a critical role in cancer cell migration and invasion. Moreover, R13 suppresses BC tumor growth and metastasis in nude mice. These data highlight the important role of R13 in BC cell proliferation and progression and suggest that R13 may be a useful drug for BC therapy. PMID- 26810191 TI - Diagnostic value of neutrophil gelatinase-associated lipocalin/matrix metalloproteinase-9 pathway in transitional cell carcinoma of the bladder. AB - Neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase (MMP) 9, and NGAL/MMP-9 complex have been evaluated as diagnostic markers of several cancers, but results for bladder cancer are scanty. We evaluated these proteins in urine and serum of 89 patients with histologically confirmed bladder cancer and 119 cancer-free controls from a case-control study. Urinary concentrations were standardized on creatinine level. The performance of these proteins as cancer biomarkers was evaluated through the receiver operating characteristic (ROC) analysis. Urinary level of NGAL, MMP-9, and NGAL/MMP-9 complex was higher in current smokers, whereas no impact of dietary habits was observed. After adjusting for tobacco smoking, urinary concentration of MMP-9 was independently associated with cancer invasiveness, grading, and histological subtype, with elevated concentrations among T2-T4 and non-papillary bladder cancers. Conversely, NGAL and NGAL/MMP-9 complex were significantly higher in non papillary than in papillary subtype. The pattern was less clear in serum, but correlation between urinary and serum concentration was poor, especially for Ta/is-T1 tumors. The ROC analysis confirmed that MMP-9 was the best marker (area under the ROC curve (AUC) = 0.68). Performances were much greater for muscle invasive bladder cancers (AUC = 0.90), with elevated negative predictive values (97 %). The present study suggests that NGAL/MMP-9 pathway is associated with an aggressive phenotype of bladder cancer. The elevated negative predictive value of MMP-9 and NGAL/MMP-9 complex makes them candidate markers of exclusion test for bladder cancer. These proteins may be integrated in the surveillance of bladder cancer, thus diminishing patients' discomfort and improving compliance. PMID- 26810190 TI - The tumor promoting roles of HSP60 and HIF2alpha in gastric cancer cells. AB - The roles of HSP60 and HIF2alpha in diagnosis, prognosis, and prevention and treatment of various human cancers have been detected. However, the combined roles of HSP60 and HIF2alpha on the prognosis of patients with gastric cancer remain unclear. In this work, we confirmed that the levels of HSP60 and HIF2alpha messenger RNA (mRNA) and protein were higher in gastric cancer tissues than that in matched normal tissues by using real-time PCR and Western blot. Furthermore, we confirmed that inhibition of HSP60 or HIF2alpha could induce apoptosis and inhibit cell mobility. Co-immunoprecipitation (co-IP) was performed to determine the interaction between HSP60 and HIF2alpha. Lastly, we confirmed that knockdown of HSP60 or HIF2alpha induced apoptosis in gastric cancer cells is negatively related to the MEK/ERK signaling in vitro. In summary, HSP60 or HIF2alpha protein expression may be a predictive marker for the prognosis of the patients with gastric cancer. Targeting HSP60 and HIF2alpha could be a future strategy to improve survival of gastric patients with poor prognosis. PMID- 26810192 TI - Chronic rupture of the long head of the biceps tendon: comparison of 2-year results following primary versus revision open subpectoral biceps tenodesis. AB - INTRODUCTION: The purpose of this study was to evaluate the clinical results of surgical repair for proximal long head of the biceps (LHB) tendon ruptures comparing chronic primary and postsurgical revision LHB tendon ruptures. MATERIALS AND METHODS: Patients who underwent subpectoral LHB tenodesis for chronic ruptures with a minimum of 2 years from surgery were identified. ASES and SF-12 PCS scores and surgical and demographic data were collected prospectively. At final follow-up, patients were interviewed regarding symptoms related to their biceps. Symptoms were converted into a Subjective Proximal Biceps Score (SPBS). RESULTS: Twenty-seven patients (22 males, 5 females) with a mean age of 61 years (range 40-76 years) underwent LHB tenodeses. Twenty patients (74.1 %) were primary repairs for chronic ruptures and seven patients (25.9 %) were revision repairs after failed prior LHB tenodesis. Twenty-five patients (92.6 %; n = 18 primary; n = 7 revision) were available for follow-up a mean of 3.8 years (range 2-6.1). The overall median postoperative SPBS showed significant improvement over the preoperative baseline (p < 0.001). Individual components of the SPBS showed substantial improvements. The SPBS significantly correlated with the postoperative ASES score (r = -0.478; p = 0.038). There were no differences in postoperative SPBSs between the primary and revision tenodesis groups. The mean postoperative ASES score was 90.3 and SF-12 PCS was 52.6. CONCLUSIONS: Open subpectoral LHB tenodesis was a safe and effective method for the treatment of chronic LHB tendon ruptures and for the revision of failed post-surgical LHB ruptures. Patients had less pain, cramping, and deformity after LHB tenodesis. The SPBS, ASES, and SF-12 PCS scores significantly improved among this group of patients. LEVEL OF EVIDENCE: Level III; Retrospective comparative study. PMID- 26810193 TI - Biosolids reduction by the oxic-settling-anoxic process: Impact of sludge interchange rate. AB - The impact of sludge interchange rate (SIR) on sludge reduction by oxic-settling anoxic (OSA) process was investigated. The sludge yield of an OSA system (a sequencing batch reactor, SBR, integrated with external anoxic reactors) was compared to that of a control (an SBR attached to a single-pass aerobic digester). SIR (%) is the percentage by volume of sludge returned from the external reactor into the main bioreactor of the OSA, and was varied from 0% to 22%. OSA achieved greater sludge reduction when fed with unsettled sewage (sCOD=113mg/L) rather than settled sewage (sCOD=60mg/L). The SIR of 11% resulted in the highest OSA performance. At the optimum SIR, higher volatile solids destruction and nitrification/denitrification (i.e., conversion of destroyed volatile solids into inert forms) were observed in the external anoxic and intermittently aerated (i.e., aerobic/anoxic) reactors, respectively. Denitrification in the aerobic/anoxic reactor was inefficient without SIR. Effluent quality and sludge settleability of the main SBR were unaffected by SIR. PMID- 26810194 TI - Diabetic mastopathy: imaging features and the role of image-guided biopsy in its diagnosis. AB - PURPOSE: The goal of this study was to evaluate the imaging features of diabetic mastopathy (DMP) and the role of image-guided biopsy in its diagnosis. METHODS: Two experienced radiologists retrospectively reviewed the mammographic and sonographic images of 19 pathologically confirmed DMP patients. The techniques and results of the biopsies performed in each patient were also reviewed. RESULTS: Mammograms showed negative findings in 78% of the patients. On ultrasonography (US), 13 lesions were seen as masses and six as non-mass lesions. The US features of the mass lesions were as follows: irregular shape (69%), oval shape (31%), indistinct margin (69%), angular margin (15%), microlobulated margin (8%), well-defined margin (8%), heterogeneous echogenicity (62%), hypoechoic echogenicity (38%), posterior shadowing (92%), parallel orientation (100%), the absence of calcifications (100%), and the absence of vascularity (100%). Based on the US findings, 17 lesions (89%) were classified as Breast Imaging Reporting and Data System category 4 and two (11%) as category 3. US-guided core biopsy was performed in 18 patients, and 10 (56%) were diagnosed with DMP on that basis. An additional vacuum-assisted biopsy was performed in seven patients and all were diagnosed with DMP. CONCLUSION: The US features of DMP were generally suspicious for malignancy, whereas the mammographic findings were often negative or showed only focal asymmetry. Core biopsy is an adequate method for initial pathological diagnosis. However, since it yields non-diagnostic results in a considerable number of cases, the evaluation of correlations between imaging and pathology plays an important role in the diagnostic process. PMID- 26810195 TI - Usefulness of strain elastography of the musculoskeletal system. AB - Ultrasound elastography is a widely used technique for assessing the mechanical characteristics of tissues. Although there are several ultrasound elastography techniques, strain elastography (SE) is currently the most widely used technique for visualizing an elastographic map in real time. Among its various indications, SE is especially useful in evaluating the musculoskeletal system. In this article, we review the SE techniques for clinical practice and describe the images produced by these techniques in the context of the musculoskeletal system. SE provides information about tissue stiffness and allows real-time visualization of the image; however, SE cannot completely replace gray-scale, color, or power Doppler ultrasonography. SE can increase diagnostic accuracy and may be useful for the follow-up of benign lesions. PMID- 26810196 TI - Thyroid nodules with isolated macrocalcification: malignancy risk and diagnostic efficacy of fine-needle aspiration and core needle biopsy. AB - PURPOSE: This study was performed to determine the malignancy risk of thyroid nodules with isolated macrocalcification and to evaluate the diagnostic efficacy of fine-needle aspiration (FNA) and core needle biopsy (CNB). METHODS: From May 2008 to December 2014, a total of 44 patients with isolated macrocalcifications were enrolled from 4,081 consecutive patients who underwent FNA or CNB at a single institution. We assessed the malignancy risk of nodules with isolated macrocalcification. We compared the diagnostic results between FNA and CNB, and the diagnostic efficacy of each procedure was evaluated by the rate of inconclusive results. We compared the diagnostic performance for malignancy between FNA and CNB with a criterion of malignant or atypia/follicular lesion of undetermined significance (indeterminate) diagnostic results. We investigated whether the ultrasonographic feature of isolated macrocalcification was predictive of malignancy. RESULTS: The malignancy risk of nodules with isolated macrocalcification was 16.1% in 31 nodules with final diagnoses and 11.4% in all nodules. CNB demonstrated a significantly lower rate of nondiagnostic and inconclusive results than FNA (7.7% vs. 53.8%, P=0.002 and 15.4% vs. 57.7%, P=0.003, respectively) in 26 nodules that underwent both FNA and CNB. CNB showed a marginally higher diagnostic performance for identifying malignancy than FNA (P=0.067). The ultrasonographic features of the anterior margin of isolated macrocalcification were not predictive of malignancy (P>0.999). CONCLUSION: Thyroid nodules with isolated macrocalcification had a low to intermediate malignancy risk and should not be considered benign nodules. CNB showed a higher diagnostic efficacy than FNA in these nodules. PMID- 26810197 TI - Metabolite profiles of repeatedly sampled urine from male fathead minnows (Pimephales promelas) contain unique lipid signatures following exposure to anti androgens. AB - The purpose of this study was twofold. First, we sought to identify candidate markers of exposure to anti-androgens by analyzing endogenous metabolite profiles in the urine of male fathead minnows (mFHM, Pimephales promelas). Based on earlier work, we hypothesized that unidentified lipids in the urine of mFHM were selectively responsive to exposure to androgen receptor antagonists, which is otherwise difficult to confirm using established fish toxicity assays. A second goal was to evaluate the feasibility of non-lethally and repeatedly sampling urine from individual mFHMs over the time course of response to a chemical exposure. Accordingly, we exposed mFHM to the model anti-androgens vinclozolin or flutamide. Urine was collected from each fish at 48hour intervals over the course of a 14day exposure. Parallel experiments were conducted with mFHM exposed to bisphenol A or control water. The frequent handling/sampling regime did not cause apparent adverse effects on the fish. Endogenous metabolite profiling was conducted with gas chromatography-mass spectrometry (GC-MS), which exhibited lower variation for the urinary metabolome than was found in earlier work with nuclear magnetic resonance (NMR) spectroscopy. Specifically, for inter- and intra individual variations, the median spectrum-wide relative standard deviation (RSD) was 32.6% and 33.3%, respectively, for GC-MS analysis of urine from unexposed mFHM. These results compared favorably with similar measurements of urine from other model species, including the Sprague Dawley rat. In addition, GC-MS allowed us to identify several lipids (e.g., certain saturated fatty acids) in mFHM urine as candidate markers of exposure to androgen receptor antagonists. PMID- 26810198 TI - Orotate phosphoribosyl transferase MoPyr5 is involved in uridine 5'-phosphate synthesis and pathogenesis of Magnaporthe oryzae. AB - Orotate phosphoribosyl transferase (OPRTase) plays an important role in de novo and salvage pathways of nucleotide synthesis and is widely used as a screening marker in genetic transformation. However, the function of OPRTase in plant pathogens remains unclear. In this study, we characterized an ortholog of Saccharomyces cerevisiae Ura5, the OPRTase MoPyr5, from the rice blast fungus Magnaporthe oryzae. Targeted gene disruption revealed that MoPyr5 is required for mycelial growth, appressorial turgor pressure and penetration into plant tissues, invasive hyphal growth, and pathogenicity. Interestingly, the ?Mopyr5 mutant is also involved in mycelial surface hydrophobicity. Exogenous uridine 5'-phosphate (UMP) restored vegetative growth and rescued the defect in pathogenicity on detached barley and rice leaf sheath. Collectively, our results show that MoPyr5 is an OPRTase for UMP biosynthesis in M. oryzae and indicate that UTP biosynthesis is closely linked with vegetative growth, cell wall integrity, and pathogenicity of fungus. Our results also suggest that UMP biosynthesis would be a good target for the development of novel fungicides against M. oryzae. PMID- 26810199 TI - Archaeal community in a human-disturbed watershed in southeast China: diversity, distribution, and responses to environmental changes. AB - The response of freshwater bacterial community to anthropogenic disturbance has been well documented, yet the studies of freshwater archaeal community are rare, especially in lotic environments. Here, we investigated planktonic and benthic archaeal communities in a human-perturbed watershed (Jiulong River Watershed, JRW) of southeast China by using Illumina 16S ribosomal RNA gene amplicon sequencing. The results of taxonomic assignments indicated that SAGMGC-1, Methanobacteriaceae, Methanospirillaceae, and Methanoregulaceae were the four most abundant families in surface waters, accounting for 12.65, 23.21, 18.58 and 10.97 % of planktonic communities, whereas Nitrososphaeraceae and Miscellaneous Crenarchaeotic Group occupied more than 49 % of benthic communities. The compositions of archaeal communities and populations in waters and sediments were significantly different from each other. Remarkably, the detection frequencies of families Methanobacteriaceae and Methanospirillaceae, and genera Methanobrevibacter and Methanosphaera in planktonic communities correlated strongly with bacterial fecal indicator, suggesting some parts of methanogenic Archaea may come from fecal contamination. Because soluble reactive phosphorus (SRP) and the ratio of dissolved inorganic nitrogen to SRP instead of nitrogen nutrients showed significant correlation with several planktonic Nitrosopumilus- and Nitrosotalea-like OTUs, Thaumarchaeota may play an unexplored role in biogeochemical cycling of river phosphorus. Multivariate statistical analyses revealed that the variation of alpha-diversity of planktonic archaeal community was best explained by water temperature, whereas nutrient concentrations and stoichiometry were the significant drivers of beta-diversity of planktonic and benthic communities. Taken together, these results demonstrate that the structure of archaeal communities in the JRW is sensitive to anthropogenic disturbances caused by riparian human activities. PMID- 26810200 TI - Tafuketide, a phylogeny-guided discovery of a new polyketide from Talaromyces funiculosus Salicorn 58. AB - A phylogeny-guided approach was applied to screen endophytic fungi containing type I polyketide synthase (PKS I) biosynthetic gene sequences and aimed to correlate genotype to chemotype for the discovery of novel bioactive polyketides. Salicorn 58, which was identified as Talaromyces funiculosus based on its internal transcribed spacer (ITS) and ribosomal large-subunit (LSU) DNA sequences, showed significant target bands. A chemical investigation of the culture of Salicorn 58 was allowed for the isolation of a new polyketide, Talafun (1), and a new natural product, N-(2'-hydroxy-3'-octadecenoyl)-9-methyl-4,8 sphingadienin (2), together with six known compounds, including chrodrimanin A (3), chrodrimanin B (4), N-(4-hydroxy-2-methoxyphenyl) acetamide (5), butyl beta glucose (6), 3beta,15beta-dihydroxyl-(22E, 24R)-ergosta-5,8(14),22-trien-7-dione (7), and (3beta,5a,8a,22E)-5,8-epidioxyergosta-6,22-dien-3-ol (8). Their chemical structures were elucidated by extensive spectroscopic analysis and electro circular dichroism (ECD) spectrum calculations. Antioxidant experiments revealed that compound 5 showed strong ABTS(+) radical scavenging activity with an IC50 value of 11.43 +/- 1.61 MUM and potent ferric reducing activity (FRAP assay) with FRAP value of 187.52 +/- 2.97. Antimicrobial assays revealed that compounds 1 and 4 showed high levels of selectivity toward Escherichia coli with MIC values of 18 +/- 0.40 and 43 +/- 0.52 MUM, respectively. Compounds 2 and 3 exhibited broad spectrum antimicrobial activity against Staphylococcus aureus, Mycobacterium smegmatis, Micrococcus tetragenus, Mycobacterium phlei, and E. coli, respectively. The results from the current research highlight the advantage of phylogeny-guided pipeline for the screening of new polyketides from endophytic fungi containing PKS I genes. PMID- 26810201 TI - Threonine aldolases: perspectives in engineering and screening the enzymes with enhanced substrate and stereo specificities. AB - Threonine aldolases have emerged as a powerful tool for asymmetric carbon-carbon bond formation. These enzymes catalyse the unnatural aldol condensation of different aldehydes and glycine to produce highly valuable beta-hydroxy-alpha amino acids with complete stereocontrol at the alpha-carbon and moderate specificity at the beta-carbon. A range of microbial threonine aldolases has been recently recombinantly produced by several groups and their biochemical properties were characterized. Numerous studies have been conducted to improve the reaction protocols to enable higher conversions and investigate the substrate scope of enzymes. However, the application of threonine aldolases in organic synthesis is still limited due to often moderate yields and low diastereoselectivities obtained in the aldol reaction. This review briefly summarizes the screening techniques recently applied to discover novel threonine aldolases as well as enzyme engineering and mutagenesis studies which were accomplished to improve the catalytic activity and substrate specificity. Additionally, the results from new investigations on threonine aldolases including crystal structure determinations and structural-functional characterization are reviewed. PMID- 26810202 TI - High-Grade Neuroendocrine Colorectal Carcinomas: A Retrospective Study of 100 Patients. AB - BACKGROUND: Colorectal high-grade neuroendocrine carcinomas (HGNEC) are a rare but aggressive group of malignancies without standard management recommendations. METHODS: We retrospectively reviewed the records of 100 consecutive patients with histologically confirmed colorectal HGNEC diagnosed at MD Anderson Cancer Center between 1991 and 2013. RESULTS: In our cohort, most tumors (89%) were small cell carcinoma, and most (60%) involved the sigmoid or the anorectal regions. Sixty four patients (64%) presented with metastatic disease at diagnosis. Striking epidemiological and clinical differences between those established in small cell lung cancer (SCLC) and our cohort were noted, including significantly lower rates of smoking and lower risk of bone, brain metastases. Over 30% of the tumors were found associated with an adenoma. Median overall survival (OS) of the cohort was 14.7 months, with 2-year and 5-year OS rates of 23% and 8%, respectively. In patients with localized disease, multimodality therapy was associated with a trend toward improved median OS (20.4 vs. 15.4 months; P = .08). Metastases at presentation (OS 20.63 vs. 8.7 months; localized vs metastatic disease at presentation; P < .001) and elevated lactate dehydrogenase levels were strongly associated with a worse outcome. CONCLUSION: In comparison to SCLC, less than half of the patients with colorectal HGNEC have history of smoking; metastatic patterns are also different between the 2 cancers. Nevertheless, HGNEC also has an aggressive biology, with the rectum being the most common site of origin. For localized disease, a multimodality approach seems to be associated with better outcomes, while systemic chemotherapy is the mainstay of treatment for advanced disease. PMID- 26810205 TI - All-comer treatment with bioresorbable vascular scaffold. AB - BACKGROUND: Bioresorbable vascular scaffolds (BVS) could overcome drug-eluting stents (DES) drawbacks connected with their permanent presence in the vessel wall. Studies exploring the clinical use of BVS are limited to the patients presenting with noncomplex, short and stable lesions. There are no prospective and randomized studies available in all-comer patients. METHODS AND RESULTS: We analyzed 31 patients, who received at least one BVS (Absorb(TM)) between September 1, 2012 and November 1, 2014. Median follow-up period was 424 days. In one (3.2%) patient, we performed a target vessel revascularization (TVR). The death rate was 6.5%. One (3.2%) patient, who received both BVS and a bare metal stent (BMS), died of an acute stent thrombosis 8 days after the initial procedure. One (3.2%) patient died of a non-cardiac death. We did not encounter any target lesion revascularization (TLR) or myocardial infarction (MI). The major adverse cardiac events (MACE) rate was 3.2%. CONCLUSIONS: Implantation of BVS is a safe treatment option. Lesions should be carefully selected and prepared before BVS implantation. We need more data about the safety of BVS and BMS overlapping. PMID- 26810206 TI - Autosomal dominant tubulointerstitial kidney disease caused by uromodulin mutations: seek and you will find. AB - BACKGROUND: Uromodulin (UMOD)-associated kidney disease belongs to the group of autosomal dominant interstitial kidney diseases and is caused by mutations in the UMOD gene. Affected patients present with hyperuricemia, gout, and progressive renal failure. The disease is thought to be very rare but is probably underdiagnosed. METHODS: Two index patients from two families with tubulointerstitial nephropathy and hyperuricemia were examined, including blood and urine chemistry, ultrasound, and mutation analysis of the UMOD gene. In addition, other available family members were studied. RESULTS: In a 46-year-old female patient with a fractional excretion of uric acid of 3 %, analysis of the UMOD gene revealed a p.W202S missense mutation. The same mutation was found in her 72-year-old father, who suffers from gout and end-stage renal disease. The second index patient was a 47-year-old female with chronic kidney disease and gout for more than 10 years. Her fractional uric acid excretion was 3.5 %. Genetic analysis identified a novel p.H250Q UMOD mutation that was also present in her 12-year-old son, who had normal renal function and uric acid levels. CONCLUSION: In patients suffering from chronic tubulointerstitial nephropathy, hyperuricemia, and a low fractional excretion of uric acid mutation, analysis of the UMOD gene should be performed to diagnose UMOD-associated kidney disease. PMID- 26810208 TI - Development and testing of a prototype tool for integrated assessment of chemical status in marine environments. AB - We report the development and application of a prototype tool for integrated assessment of chemical status in aquatic environments based on substance- and matrix-specific environmental assessment criteria (thresholds). The Chemical Status Assessment Tool (CHASE) integrates data on hazardous substances in water, sediments and biota as well as bio-effect indicators and is based on a substance- or bio-effect-specific calculation of a 'contamination ratio' being the ratio between an observed concentration and a threshold value. Values <1.0 indicate areas potentially 'unaffected', while values >1.0 indicate areas potentially 'affected'. These ratios are combined within matrices, i.e. for water, sediment and biota and for biological effects. The overall assessment used a 'one out, all out principle' with regard to each matrix. The CHASE tool was tested in the Baltic Sea and the North Sea in 376 assessment units. In the former, the chemical status was >1.0 in practically all areas indicating that all areas assessed were potentially affected. The North Sea included areas classified as unaffected or affected. The CHASE tool can in combination with temporal trend assessments of individual substances be advantageous for use in remedial action plans and, in particular, for the science-based evaluation of the status and for determining which specific substances are responsible for a status as potentially affected. PMID- 26810209 TI - Erratum to: Phytoplankton variability in relation to some environmental factors in the eastern coast of Suez Gulf, Egypt. PMID- 26810210 TI - Cutaneous metastasis of rhabdomyosarcoma. PMID- 26810213 TI - Staying connected or networked to death? PMID- 26810212 TI - Chemical composition, antioxidant and anticholinesterase potentials of essential oil of Rumex hastatus D. Don collected from the North West of Pakistan. AB - BACKGROUND: Ethnomedicinally Rumex hastatus D. Don has been used since long for various ailments especially in neurological disorders. The reported data and the importance of Rumex genus demonstrate the vital medicinal value of R. hastatus. METHODS: In the current investigational study, isolation of essential oil and its antioxidant and anticholinesterase assays were performed. The essential oil of R. hastatus was analyzed by GC-MS for the first time. The essential oil was evaluated for anticholinesterase and antioxidant assays. The anticholinesterase assay was conducted at various concentrations (62.5 to 1000 MUg/ml) against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Similarly, the antioxidant potential was determined using DPPH and ABTS free radicals. RESULTS: The GC-MS analysis of essential oil showed 123 components. The result recorded for the anticholinesterase assays demonstrated a marked potential against AChE and BChE with IC50 values of 32.54 and 97.38 MUg/ml respectively which were comparable with the positive control i.e., galanthamine (AChE, IC50 = 4.73 MUg/ml and BChE, IC50 = 11.09 MUg/ml). The antioxidant assays against DPPH and ABTS free radicals also exhibited significant scavenging potential with IC50 values of 3.71 and 6.29 MUg/ml respectively, while for ascorbic acid the IC50 value was <0.1 MUg/ml against both free radicals. CONCLUSIONS: Based on the current investigational studies, it may be concluded that R. hastatus is an effective source of essential oil's components having anticholinesterase and antioxidant potentials, which after subjecting to drug development may lead to novel drug candidates against neurodegenerative disorders. PMID- 26810214 TI - Advances in management and utilization of invasive water hyacinth (Eichhornia crassipes) in aquatic ecosystems - a review. AB - The objective of this review is to provide a concise summary of literature in the Chinese language since late 1970s and focuses on recent development in global scenarios. This work will replenish the FAO summary of water hyacinth utilization from 1917 to 1979 and review ecological and socioeconomic impacts of the water hyacinth from 1980 to 2010. This review also discusses the debate on whether the growth of the water hyacinth is a problem, a challenge or an opportunity. Literature suggested that integrated technologies and good management may be an effective solution and the perception of water hyacinth could change from that of a notorious aquatic weed to a valuable resource, including its utilization as a biological agent for the application in bioremediation for removing excess nutrients from eutrophic water bodies at low cost. Key aspects on system integration and innovation may focus on low-cost and efficient equipment and the creation of value-added goods from water hyacinth biomass. In the socioeconomic and ecological domain of global development, all the successful and sustainable management inputs for the water hyacinth must generate some sort of social and economic benefit simultaneously, as well as benefiting the ecosystem. Potential challenges exist in linkages between the management of water hyacinth on the large scale to the sustainable development of agriculture based on recycling nutrients, bio-energy production or silage and feed production. Further research and development may focus on more detailed biology of water hyacinth related with its utilization, cost-benefit analysis of middle to large-scale application of the technologies and innovation of the equipment used for harvesting and dehydrating the plant. PMID- 26810215 TI - Bovine respiratory syncytial virus outbreak reduced bulls' weight gain and feed conversion for eight months in a Norwegian beef herd. AB - BACKGROUND: Cost-benefit evaluation of measures against respiratory disease in cattle requires accounting with the associated production losses. Investigations of naturally occurring respiratory infections in a herd setting are an opportunity for accurate estimates of the consequences. This article presents estimates based on individual monitoring of weight and concentrate intake of several hundred bulls previous to, during and after a respiratory infection outbreak with bovine respiratory syncytial virus (BRSV) as the main pathogen. The aim of the study was to analyse the association between exposure to BRSV, weight gain and feed conversion rate, quantify any change in these parameters, and estimate the duration of the change in production. RESULTS: A comparison of growth curves for the bulls that were present during the outbreak revealed that bulls with severe clinical signs had a clear and consistent trend of poorer growth rate than those with milder or no signs. The weight/age-ratio was 0.04 0.10 lower in the severely affected bulls, and evident throughout the study period of 8 months. A comparison of growth rates between apparently healthy bulls being present during the outbreak and a comparable group of bulls exactly 1 year later (n = 377) showed a reduced growth rate of 111 g/day in the first group. The difference amounted to 23 extra days needed to reach the reference weight. Feed conversion was also reduced by 79 g weight gain/kilogram concentrate consumed in the outbreak year. CONCLUSION: This study indicates significant negative effects on performance of animals that develop severe clinical signs in the acute stage, and that the growth and production is negatively affected many months after apparent recovery. In addition, the performance of apparently healthy animals that are exposed during an outbreak are severely negatively affected. The duration of this decrease in production in animals after recovery, or animals that have not shown disease at all, has not previously been documented. These losses will easily be underestimated, but contribute significantly to the costs for the producer. The findings emphasize the importance of BRSV infection for profitability and animal welfare in cattle husbandry. The study also illustrates that utilising intra-herd comparison of health and production parameters is a productive approach to estimate consequences of an outbreak. PMID- 26810217 TI - Partner status and mental and physical health of independently living men aged 70 years and older. AB - AIM: To describe and compare the mental health and physical functioning of community-dwelling men aged 70 years and over who live alone, and those who live with their partner/spouse. METHOD: Data were obtained from the baseline survey of the New South Wales 45 and Up Study. Mental health was measured using the Kessler Psychological Distress Scale and physical health was measured using the Medical Outcome Short Form 36 physical functioning scale. RESULTS: 37 690 community dwelling men aged 70 years or over were included in the analyses. Men living alone were more likely to have high psychological distress scores and lower physical functioning scores compared to men living with a spouse/partner within each age group, except those 85 and over. CONCLUSIONS: Specific health and welfare programs targeted to the increasing number of older men living alone may be needed to address their higher levels of psychological distress and lower levels of physical functioning. PMID- 26810219 TI - Sea urchin-like cobalt-iron phosphide as an active catalyst for oxygen evolution reaction. AB - Sea urchin-like (CoxFe1-x)2P shows Co/Fe-composition dependent catalysis for oxygen evolution reaction (OER) in 0.1 M KOH. The (Co0.54Fe0.46)2P is the most efficient OER catalyst, reaching 10 mA cm(-2) at an overpotential of 0.37 V (vs. RHE). The report offers a new synergistic approach to tune and optimize the electrocatalysis of OER. PMID- 26810218 TI - How to survey classical swine fever in wild boar (Sus scrofa) after the completion of oral vaccination? Chasing away the ghost of infection at different spatial scales. AB - Oral mass vaccination (OMV) is considered as an efficient strategy for controlling classical swine fever (CSF) in wild boar. After the completion of vaccination, the presence of antibodies in 6-12 month-old hunted wild boars was expected to reflect a recent CSF circulation. Nevertheless, antibodies could also correspond to the long-lasting of maternal antibodies. This paper relates an experience of surveillance which lasted 4 years after the completion of OMV in a formerly vaccinated area, in north-eastern France (2010-2014). First, we conducted a retrospective analysis of the serological data collected in 6-12 month-old hunted wild boars from 2010 up to 2013, using a spatial Bayesian model accounting for hunting data autocorrelation and heterogeneity. At the level of the whole area, seroprevalence in juvenile boars decreased from 28% in 2010-2011 down to 1% in 2012-2013, but remained locally high (above 5%). The model revealed the existence of one particular seroprevalence hot-spot where a longitudinal survey of marked animals was conducted in 2013-2014, for deciphering the origin of antibodies. Eleven out of 107 captured piglets were seropositive when 3-4 months-old, but their antibody titres progressively decreased until 6-7 months of age. These results suggest piglets were carrying maternal antibodies, few of them carrying maternal antibodies lasting until the hunting season. Our study shows that OMV may generate confusion in the CSF surveillance several years after the completion of vaccination. We recommend using quantitative serological tools, hunting data modelling and capture approaches for better interpreting serological results after vaccination completion. Surveillance perspectives are further discussed. PMID- 26810220 TI - Systematic review to understand and improve care after stillbirth: a review of parents' and healthcare professionals' experiences. AB - BACKGROUND: 2.7 million babies were stillborn in 2015 worldwide; behind these statistics lie the experiences of bereaved parents. The first Lancet series on stillbirth in 2011 described stillbirth as one of the "most shamefully neglected" areas of public health, recommended improving interaction between families and frontline caregivers and made a plea for increased investment in relevant research. METHODS: A systematic review of qualitative, quantitative and mixed method studies researching parents and healthcare professionals experiences of care after stillbirth in high-income westernised countries (Europe, North America, Australia and South Africa) was conducted. The review was designed to inform research, training and improve care for parents who experience stillbirth. RESULTS: Four thousand four hundred eighty eight abstracts were identified; 52 studies were eligible for inclusion. Synthesis and quantitative aggregation (meta summary) was used to extract findings and calculate frequency effect sizes (FES%) for each theme (shown in italics), a measure of the prevalence of that finding in the included studies. Researchers' areas of interest may influence reporting of findings in the literature and result in higher FES sizes, such as; support memory making (53%) and fathers have different needs (18%). Other parental findings were more unexpected; Parents want increased public awareness (20%) and for stillbirth care to be prioritised (5%). Parental findings highlighted lessons for staff; prepare parents for vaginal birth (23%), discuss concerns (13%), give options & time (20%), privacy not abandonment (30%), tailored post-mortem discussions (20%) and post-natal information (30%). Parental and staff findings were often related; behaviours and actions of staff have a memorable impact on parents (53%) whilst staff described emotional, knowledge and system-based barriers to providing effective care (100%). Parents reported distress being caused by midwives hiding behind 'doing' and ritualising guidelines whilst staff described distancing themselves from parents and focusing on tasks as coping strategies. Parents and staff both identified the need for improved training (parents 25% & staff 57%); continuity of care (parents 15% & staff 36%); supportive systems & structures (parents 50%); and clear care pathways (parents 5%). CONCLUSIONS: Parents' and healthcare workers' experiences of stillbirth can inform training, improve the provision of care and highlight areas for future research. PMID- 26810221 TI - Eotaxin-Rich Proangiogenic Hematopoietic Progenitor Cells and CCR3+ Endothelium in the Atopic Asthmatic Response. AB - Angiogenesis is closely linked to and precedes eosinophilic infiltration in asthma. Eosinophils are recruited into the airway by chemoattractant eotaxins, which are expressed by endothelial cells, smooth muscles cells, epithelial cells, and hematopoietic cells. We hypothesized that bone marrow-derived proangiogenic progenitor cells that contain eotaxins contribute to the initiation of angiogenesis and inflammation in asthma. Whole-lung allergen challenge of atopic asthma patients revealed vascular activation occurs within hours of challenge and before airway inflammation. The eotaxin receptor CCR3 was expressed at high levels on submucosal endothelial cells in patients and a murine model of asthma. Ex vivo exposure of murine endothelial cells to eotaxins induced migration and angiogenesis. In mechanistic studies, wild-type mice transplanted with eotaxin 1/2-deficient bone marrow had markedly less angiogenesis and inflammation in an atopic asthma model, whereas adoptive transfer of proangiogenic progenitor cells from wild-type mice in an atopic asthma model into the eotaxin-1/2-deficient mice led to angiogenesis and airway inflammation. The findings indicate that Th2 promoting hematopoietic progenitor cells are rapidly recruited to the lung upon allergen exposure and release eotaxins that coordinately activate endothelial cells, angiogenesis, and airway inflammation. PMID- 26810222 TI - Yeast-Derived Particulate beta-Glucan Treatment Subverts the Suppression of Myeloid-Derived Suppressor Cells (MDSC) by Inducing Polymorphonuclear MDSC Apoptosis and Monocytic MDSC Differentiation to APC in Cancer. AB - Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that promote tumor progression. In this study, we demonstrated that activation of a C-type lectin receptor, dectin-1, in MDSC differentially modulates the function of different MDSC subsets. Yeast-derived whole beta-glucan particles (WGP; a ligand to engage and activate dectin-1, oral treatment in vivo) significantly decreased tumor weight and splenomegaly in tumor bearing mice with reduced accumulation of polymorphonuclear MDSC but not monocytic MDSC (M-MDSC), and decreased polymorphonuclear MDSC suppression in vitro through the induction of respiratory burst and apoptosis. On a different axis, WGP-treated M-MDSC differentiated into F4/80(+)CD11c(+) cells in vitro that served as potent APC to induce Ag-specific CD4(+) and CD8(+) T cell responses in a dectin-1-dependent manner. Additionally, Erk1/2 phosphorylation was required for the acquisition of APC properties in M-MDSC. Moreover, WGP-treated M-MDSC differentiated into CD11c(+) cells in vivo with high MHC class II expression and induced decreased tumor burden when inoculated s.c. with Lewis lung carcinoma cells. This effect was dependent on the dectin-1 receptor. Strikingly, patients with non-small cell lung carcinoma that had received WGP treatment for 10-14 d prior to any other treatment had a decreased frequency of CD14(-)HLA-DR( )CD11b(+)CD33(+) MDSC in the peripheral blood. Overall, these data indicate that WGP may be a potent immune modulator of MDSC suppressive function and differentiation in cancer. PMID- 26810223 TI - Ptpn22 Modifies Regulatory T Cell Homeostasis via GITR Upregulation. AB - PTPN22 gene variation associates with multiple autoimmune diseases, including type 1 diabetes and rheumatoid arthritis. Loss of function studies have demonstrated that PTPN22 impinges on the homeostatic behavior of regulatory T (Treg) cells, a lineage critical for immune tolerance. The frequency and absolute number of Treg cells is increased in Ptpn22-deficient mice, but the mechanism driving this increase is unknown. In this study, we show that Ptpn22 knockdown (KD) promoted the expansion of the Treg cell compartment by upregulating the glucocorticoid-induced TNFR family-related protein (GITR) and increasing GITR signaling. Ptpn22 KD did not accelerate cell division but instead prolonged Treg cell survival, as measured by a decrease in the frequency of apoptotic Treg cells. Loss of Ptpn22 caused a concomitant increase in the proportion of CD44(hi)CD62L(lo) effector Treg cells, at the expense of CD44(lo)CD62L(hi) central Treg cells. The increase in Treg cell numbers, but not their differentiation toward an effector phenotype, was dependent on GITR signaling, because blockade of GITR ligand prevented Treg cell expansion caused by Ptpn22 KD. These findings indicate that GITR plays a key role in regulating the overall size of the Treg cell pool. Our results suggest that the size and composition of the Treg cell compartment are independently controlled and have implications for the design of immunotherapies that seek to improve Treg cell function. PMID- 26810224 TI - Extensive CD4 and CD8 T Cell Cross-Reactivity between Alphaherpesviruses. AB - The Alphaherpesvirinae subfamily includes HSV types 1 and 2 and the sequence divergent pathogen varicella zoster virus (VZV). T cells, controlled by TCR and HLA molecules that tolerate limited epitope amino acid variation, might cross react between these microbes. We show that memory PBMC expansion with either HSV or VZV enriches for CD4 T cell lines that recognize the other agent at the whole virus, protein, and peptide levels, consistent with bidirectional cross reactivity. HSV-specific CD4 T cells recovered from HSV-seronegative persons can be explained, in part, by such VZV cross-reactivity. HSV-1-reactive CD8 T cells also cross-react with VZV-infected cells, full-length VZV proteins, and VZV peptides, as well as kill VZV-infected dermal fibroblasts. Mono- and cross reactive CD8 T cells use distinct TCRB CDR3 sequences. Cross-reactivity to VZV is reconstituted by cloning and expressing TCRA/TCRB receptors from T cells that are initially isolated using HSV reagents. Overall, we define 13 novel CD4 and CD8 HSV-VZV cross-reactive epitopes and strongly imply additional cross-reactive peptide sets. Viral proteins can harbor both CD4 and CD8 HSV/VZV cross-reactive epitopes. Quantitative estimates of HSV/VZV cross-reactivity for both CD4 and CD8 T cells vary from 10 to 50%. Based on these findings, we hypothesize that host herpesvirus immune history may influence the pathogenesis and clinical outcome of subsequent infections or vaccinations for related pathogens and that cross reactive epitopes and TCRs may be useful for multi-alphaherpesvirus vaccine design and adoptive cellular therapy. PMID- 26810225 TI - Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis. AB - Myeloid cells, including proinflammatory monocytes and neutrophils, have important roles in the pathology of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). These cells infiltrate the CNS in the early stages of disease development and contribute to the inflammatory response that is associated with symptom severity. It is thus crucial to identify and understand new mechanisms that can regulate the CNS infiltration of proinflammatory myeloid cells. Nicotinic acetylcholine receptors (nAChRs) have been increasingly studied for their immune-regulatory properties. In this study, we assessed the ability of nicotine, an nAChR ligand, to modulate proinflammatory myeloid cell numbers within the bone marrow, spleen, blood, and CNS of EAE mice. We found that nicotine significantly inhibits the infiltration of proinflammatory monocytes and neutrophils into the CNS at time points where these cells are known to play critical roles in disease pathology. In contrast, nicotine does not affect the expansion of other monocytes. We also show that nicotine exerts these effects by acting on alpha7 and alpha9 nAChR subtypes. Finally, mRNA transcript levels for CCL2 and CXCL2, chemokines involved in the chemotaxis of proinflammatory monocytes and neutrophils, respectively, are reduced in the brain of nicotine-treated EAE mice before the massive infiltration of these cells. Taken together, our data provide evidence that nAChRs can regulate proinflammatory cell infiltration into the CNS, which could be of significant value for the treatment of neuroinflammatory disorders. PMID- 26810226 TI - Essential Role for Survivin in the Proliferative Expansion of Progenitor and Mature B Cells. AB - Survivin is a member of the inhibitor of apoptosis family of proteins and a biomarker of poor prognosis in aggressive B cell non-Hodgkin's lymphoma. In addition to its role in inhibition of apoptosis, survivin also regulates mitosis. In this article, we show that deletion of survivin during early B cell development results in a complete block at the cycling pre-B stage. In the periphery, B cell homeostasis is not affected, but survivin-deficient B cells are unable to mount humoral responses. Correspondingly, we show that survivin is required for cell division in response to mitogenic stimulation. Thus, survivin is essential for proliferation of B cell progenitors and activated mature B cells, but is dispensable for B cell survival. Moreover, a small-molecule inhibitor of survivin strongly impaired the growth of representative B lymphoma lines in vitro, supporting the validity of survivin as an attractive therapeutic target for high-grade B cell non-Hodgkin's lymphoma. PMID- 26810227 TI - Interplay between Target Sequences and Repair Pathways Determines Distinct Outcomes of AID-Initiated Lesions. AB - Activation-induced deaminase (AID) functions by deaminating cytosines and causing U:G mismatches, a rate-limiting step of Ab gene diversification. However, precise mechanisms regulating AID deamination frequency remain incompletely understood. Moreover, it is not known whether different sequence contexts influence the preferential access of mismatch repair or uracil glycosylase (UNG) to AID initiated U:G mismatches. In this study, we employed two knock-in models to directly compare the mutability of core SMU and VDJ exon sequences and their ability to regulate AID deamination and subsequent repair process. We find that the switch (S) region is a much more efficient AID deamination target than the V region. Igh locus AID-initiated lesions are processed by error-free and error prone repair. S region U:G mismatches are preferentially accessed by UNG, leading to more UNG-dependent deletions, enhanced by mismatch repair deficiency. V region mutation hotspots are largely determined by AID deamination. Recurrent and conserved S region motifs potentially function as spacers between AID deamination hotspots. We conclude that the pattern of mutation hotspots and DNA break generation is influenced by sequence-intrinsic properties, which regulate AID deamination and affect the preferential access of downstream repair. Our studies reveal an evolutionarily conserved role for substrate sequences in regulating Ab gene diversity and AID targeting specificity. PMID- 26810229 TI - [Arthroscopic tibiotalocalcaneal arthrodesis]. AB - Tibiotalocalcaneal arthrodesis (TTCA) is indicated for a variety of disorders, including end-stage osteoarthritis, severe deformities and complications after operative interventions on the upper and lower ankle joints. Due to the biomechanical advantages, TTCA is predominantly performed with curved retrograde intramedullary nails allowing compression before locking. Hindfoot arthrodesis is most commonly performed by extensive open surgical approaches. Despite a patient satisfaction rate greater than 80 %, current reviews have reported mean complication rates of more than 50 % with a pronounced variance in bone union rates. This is influenced by the sometimes severe preexisting diseases in this patient collective. A predictive risk assessment for complications following TTCA revealed a significantly increased risk in the presence of diabetes mellitus, revision surgery or preoperative ulceration. In these high-risk patients, a reduction of the invasiveness of the procedure could possibly reduce the complication rates. Arthroscopic TTCA therefore appears to be a promising alternative approach. Even though only few case reports and one case series have been published, in the total collective of 17 patients only one subtalar non union and one minor complication were reported. Despite the limited evidence available, arthroscopic TTCA appears to be a promising therapy option in patients with an increased risk profile and comorbidities, such as critical soft tissue situations, plantar ulceration, peripheral arterial occlusive disease (PAOD) and diabetes mellitus. PMID- 26810230 TI - [Arthroscopic treatment of chondral lesions of the ankle joint. Evidence-based therapy]. AB - Ankle sprains are the most relevant injuries of the lower extremities and can lead to damage to ligaments and osteochondral lesions. Up to 50 % of patients with a sprained ankle later develop a lesion of the cartilage in the ankle joint or an osteochondral lesion of the talus. This can lead to osteoarthritis of the injured ankle joint. Spontaneous healing is possible in all age groups in cases of a bone bruise in the subchondral bone but in isolated chondral injuries is only useful in pediatric patients. In many cases chondral and osteochondral injuries lead to increasing demarcation of the affected area and can result in progressive degeneration of the joint if not recognized in time. There also exist a certain number of osteochondral changes of the articular surface of the talus without any history of relevant trauma, which are collectively grouped under the term osteochondrosis dissecans. Perfusion disorders are discussed as one of many possible causes of these alterations. Nowadays, chondral and osteochondral defects can be treated earlier due to detection using very sensitive magnetic resonance imaging (MRI) and computed tomography (CT) techniques. The use of conservative treatment only has a chance of healing in pediatric patients. Conservative measures for adults should only be considered as adjuvant treatment to surgery.Based on a comprehensive analysis of the current literature, this article gives an overview and critical analysis of the current concepts for treatment of chondral and osteochondral injuries and lesions of the talus. With arthroscopic therapy curettage and microfracture of talar lesions are the predominant approaches or retrograde drilling of the defect is another option when the chondral coating is retained. Implantation of autologous chondral cells or homologous juvenile cartilage tissue is also possible with arthroscopic techniques. Osteochondral fractures (flake fracture) are usually performed as a mini-open procedure supported by arthroscopy. The use of the osteochondral autograft transfer system (OATS), implantation of membranes with or without autologous bone marrow transfer and possibly with growth factors or implantation of stem cells are carried out in combination with arthroscopic mini-open procedures. The results from the literature are discussed and compared with own results after arthroscopic treatment of chondral lesions of the talus. PMID- 26810231 TI - [Reconstruction of the palmar middle phalangeal base of the finger: Treatment with a hemi-hamate transplant]. PMID- 26810228 TI - Subclinical-Dose Endotoxin Sustains Low-Grade Inflammation and Exacerbates Steatohepatitis in High-Fat Diet-Fed Mice. AB - Subclinical circulating bacterial endotoxin LPS has been implicated as an important cofactor in the development and progression of nonalcoholic steatohepatitis, but the underlying mechanisms remain unclear. In this study, we demonstrated that 4-wk injection with superlow-dose LPS significantly promoted neutrophil infiltration and accelerated nonalcoholic steatohepatitis progression, including exacerbated macrovesicular steatosis, inflammation, and hepatocyte ballooning in high-fat diet-fed apolipoprotein E knockout mice. This effect could sustain for a month after stoppage of LPS injection. LPS also significantly increased numbers of apoptotic nuclei in hepatocytes and expressions of proapoptotic regulators. Moreover, LPS sustained the low-grade activation of p38 MAPK and inhibited the expression of the upstream MAPK phosphatase 7. By applying selective inhibitors, we demonstrated that the activation of p38 MAPKs is required for neutrophil migration induced by superlow-dose LPS in vitro. Together, these data suggest that superlow-dose LPS may sustain the low-grade activation of p38 MAPKs and neutrophil infiltration, leading to the exacerbation of steatohepatitis. PMID- 26810232 TI - Anti-inflammatory effect of fullerene C60 in a mice model of atopic dermatitis. AB - BACKGROUND: Water-soluble form of fullerene C60 is a promising tool for the control of ROS-dependent inflammation including allergic diseases. Anti inflammatory effects of C60 (nC60) aqueous dispersion were evaluated in the mouse models of atopic dermatitis using subcutaneous (SC) and epicutaneous (EC) applications during 50 days period. A highly stable nC60 was prepared by exhaustive dialysis of water-organic C60 solution against water, where the size and zeta-potential of fullerene nanoparticles are about 100 nm and -30 mV, respectively. RESULTS: To induce skin inflammation, female BALB/c mice were EC sensitized with ovalbumin three times during one-weekly exposures. The nC60 solution was administrated in mice subcutaneously (SC) (0.1 mg/kg) and epicutaneously (EC) (1 mg/kg). Significant suppression of IgE and Th2 cytokines production and a concomitant rise in concentrations of Th1 cytokines were observed in nC60-treated groups. In addition, a significant increase in the levels of Foxp3(+) and filaggrin mRNA expression was observed at EC application. Histological examination of skin samples indicated that therapeutic effect was achieved by both EC and SC treatment, but it was more effective with EC. Pronounced reduction of the eosinophil and leukocyte infiltration in treated skin samples was observed. CONCLUSIONS: We suppose that nC60 treatment shifts immune response from Th2 to Th1 and restores to some extent the function of the skin barrier. This approach can be a good alternative to the treatment of allergic and other inflammatory diseases. PMID- 26810234 TI - A Snapshot of Drug-Resistant M. tuberculosis Strains in Croatia. AB - Tuberculosis caused by resistant M. tuberculosis strains poses a serious threat as it requires prolonged and costly treatment and has high mortality rate. In order to investigate resistance to antituberculous drugs in Croatia, we analysed all resistant M. tuberculosis strains isolated from patients' samples in period 2010-2014 (1 strain per patient). Out of 2384 M. tuberculosis strains, we identified 88 (3.69 %) resistant strains. The analysis included resistance patterns, resistance conferring mutations and, according to MIRU-VNTR analysis, clustering and global lineages distribution. Relatively high number of strains was monoresistant, especially to isoniazid, while there were only six multiresistant strains. Among 59 strains with any pattern that includes resistance to isoniazid, a total of 22 (37.29 %) had resistance conferring mutation in katG gene (S315T), 23 (38.98 %) in inhA promoter region (C-15T) and 14 (23.73 %) had none of these mutations. The observed clustering rate of resistant strains was 28.41 %, and the most common global lineage was Euro American (75 %). PMID- 26810233 TI - Emergence of Escherichia coli Sequence Type 131 (ST131) and ST3948 with KPC-2, KPC-3 and KPC-8 carbapenemases from a Long-Term Care and Rehabilitation Facility (LTCRF) in Northern Italy. AB - Aim of the study was to characterize KPC-producing Escherichia coli (KPC-Ec) clinical isolates among a Northern Italy Long-Term Care and Rehabilitation Facility (LTCRF) residents. Thirteen consecutive non repeated MDR E. coli isolates showing ertapenem Minimum Inhibitory Concentrations (MICs) >0.5 mg/L, collected during the period March 2011 - May 2013 from ASP "Redaelli" inpatients, were investigated. The bla KPC/CTX-M/SHV/TEM/OXA genes were identified by PCR and sequencing. KPC-Ec isolates underwent phylotyping, Pulsed-Field Gel Electrophoresis (PFGE), multilocus sequence typing (MLST) and repetitive sequence based PCR (rep-PCR) profiling. Incompatibility groups analysis and conjugation were also performed. Eleven out of 13 isolates, resulted bla KPC-type positive, were consistently resistant to third generation cephalosporins, fluoroquinolones and trimethoprim-sulphametoxazole (84.6 %), retaining susceptibility to colistin (EUCAST guidelines). At least n = 4/11 of KPC-Ec patients received >=48 h of meropenem therapy. Sequencing identified 9 bla KPC-2, 1 bla KPC-3 and 1 bla KPC-8 determinants. KPC-Ec plasmids belonged to IncF group (FIIk replicon); conjugation confirmed bla KPC/TEM-1/OXA-9 genes transferability for 10 KPC-Ec. Although three pulsotypes (A, B, C) were identified, all KPC-Ec belonged to phylogenetic group B2. Clone B (B-B5) caused an outbreak of infection involving nine inpatients at five wards. Rep-PCR showed relatedness for seven representative KPC-Ec isolates. Here we report a LTCRF outbreak caused by a ST131-B2 E. coli associated with bla KPC-2 and bla KPC-8 genes, and the emergence of the new ST3948. Elderly people with co-morbidities are at risk for ST131 colonization. KPC-Ec clones local monitoring appears essential both to avoid their spreading among healthcare settings, and to improve therapeutic choices for LTCRF residents. PMID- 26810235 TI - Carbapenem-Resistant Klebsiella pneumoniae: Results of a Laboratory Surveillance Program in an Italian General Hospital (August 2014-January 2015) : Surveillance of Carbapenem-resistant Klebsiella pneumoniae. AB - In this study we report the analysis of 131 Klebsiella pneumoniae (K. pneumoniae) clinical isolates from patients hospitalized in various wards, of Perugia General Hospital, from August 2014 to January 2015. Forty two isolates (32.1 %), were resistant to at least one carbapenem antibiotic and, among these isolates, 14 (33.3 %) exhibited resistance to colistin. All isolates were carbapenemases producers and 41 (97.6 %) harboured the bla KPC gene. Carbapenem-resistant K. pneumoniae isolates (CRKPs) were, also, typed for the genotypic diversity and the results revealed the circulation of two major clusters.This surveillance study evidences the spread of CRKP isolates in Perugia General Hospital and confirms that carbapenem-resistant K. pneumoniae isolates have reached epidemic dissemination in Italy. In addition the percentage of resistance to colistin resulted to be less than that observed in other hospital laboratories across Italy. In conclusion the circulation of these isolates should be monitored and appropriate policy of surveillance must be used, in a target manner, in order to reduce the spread of carbapenem-resistant isolates. PMID- 26810236 TI - Rough set based rule induction in decision making using credible classification and preference from medical application perspective. AB - This paper presents a new heuristic algorithm for reduct selection based on credible index in the rough set theory (RST) applications. This algorithm is efficient and effective in selecting the decision rules particularly the problem to be solved in a large scale. This algorithm is capable to derive the rules with multi-outcomes and identify the most significant features simultaneously, which is unique and useful in solving predictive medical problems. The end results of the proposed approach are a set of decision rules that illustrates the causes for solitary pulmonary nodule and results of the long term treatment. PMID- 26810237 TI - Foreword. PMID- 26810239 TI - Does knowledge of diagnosis really affect rates of depression in cancer patients? AB - : Significant levels of distress usually accompany the entire cancer experience, affecting the patients' general functioning and adaptation to illness. OBJECTIVE: The major objective of the present study was to investigate potential demographic and intrapersonal moderators of the relationship between knowing the cancer diagnosis and the level of depression experienced. METHOD: The present research has a transversal comparative repeated cross-sectional design (2006-2014), sampling following the proportional quota method. Research was conducted in the four major oncological institutes in Romania, obtaining a national sample of cancer patients, maintaining gender and ethnic rates, and permitting the investigation of the stability of the results from one assessment to the other. RESULTS: Results indicate that in the Romanian context, knowing the diagnosis is associated with a lower level of depression than not knowing the diagnosis, the results being similar in both assessments (2006-2014). Furthermore, from the explored demographic factors (gender, residence, age, and education), only age has a main effect upon depression (depression increasing with age), while education is the only factor from those analyzed, which has a moderator effect. Regarding the analyzed intra-individual variables, only dysfunctional attitudes, emotion-focused coping, and lack of emotional support from the family (loneliness) have main effects upon the level of depression (i.e., higher levels of dysfunctional attitudes, emotion-focused coping, and loneliness are associated with higher levels of depression), while neither of them has a moderator effect on the relationship between knowing the diagnosis and depression. CONCLUSION: These results are important in the improvement of the doctor-patient relationship, the management of cancer-related distress, and implicitly for the course of illness. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26810242 TI - [Randomised clinical trial to compare two tracheotomy care methods in an Intensive Care Unit]. AB - INTRODUCTION: Tracheotomy is a common technique in Intensive Care Units (ICU). It is known that nursing care during and after that procedure is directly related to its success, by reducing the possible complications to a minimum, such as the stoma infection, and contributing to a favourable outcome in critical patients. OBJECTIVES: To compare the use of polyhexanide (PLX) versus saline+povidone iodine (PY) as antiseptics and infection incidence in tracheostomies performed in Intensive Care Units. MATERIAL AND METHOD: A 2-year, experimental, randomised, open-label trial carried out in a multidiscipline ICU with 32 beds. The study was approved by the Research Ethics Committee of Principality of Asturias. RESULTS: The overall infection rate observed for every hundred patients was 1.34 (95% CI; 0.81-2.01), with 1.46 when using PLX and 1.21 for PY (P=.685). CONCLUSIONS: In spite of the experimental treatment (PLX) was shown to be effective in other types of wounds in our study. No significant differences were found between this technique and the standard one. Since there is no national registry of tracheotomy- associated infections, it is not possible to know whether the rate observed is within the usual parameters. PMID- 26810243 TI - A rare type of ankle fracture: Syndesmotic rupture combined with a high fibular fracture without medial injury. AB - High fibular spiral fractures are usually caused by pronation-external rotation mechanism. The foot is in pronation and the talus externally rotates, causing a rupture of the medial ligaments or a fracture of the medial malleolus. With continued rotation the anterior and posterior tibiofibular ligament will rupture, and finally, the energy leaves the fibula by creating a spiral fracture from anterior superior to posterior inferior. In this article we demonstrate a type of ankle fracture with syndesmotic injury and high fibular spiral fractures without a medial component. This type of ankle fractures cannot be explained by the Lauge Hansen classification, since it lacks injury on the medial side of the ankle, but it does have the fibular fracture pattern matching the pronation external rotation injury (anterior superior to posterior inferior fracture). We investigated the mechanism of this injury illustrated by 3 cases and postulate a theory explaining the biomechanics behind this type of injury. PMID- 26810244 TI - Diethylstilbestrol-induced mouse hypospadias: "window of susceptibility". AB - This review presents published and novel results that define the programming window for diethylstilbestrol (DES)-induced abnormal development of the mouse penis. These data indicate that DES has its greatest effect during the period of most intense penile morphogenesis, namely postnatal days 0-15 (P0-P15). Pregnant mice and their neonatal pups were injected subcutaneously with 200 ng/gbw DES every other day from embryonic day 12-18 (DES E12-E18), postnatal day 0-10 (DES P0-P10), embryonic day 12 to postnatal day 10 (DES E12-P10), postnatal day 5-15 (DES P5-P15), and postnatal day 10-20 (DES P10-P20). Aged-matched controls received sesame oil vehicle. After euthanasia at 10, 15, 20 and 60 days, penises were analyzed by gross morphology, histology and morphometry. Penises of all 5 groups of DES-treated mice were reduced in size, which was confirmed by morphometric analysis of internal penile structures. The most profound effects were seen in the DES E12-P10, DES P0-P10, and DES P5-P15 groups, thus defining a DES "programming window". For all parameters, DES treatment from P10 to P20 showed the most mild of effects. Adverse effects of DES on the MUMP cartilage and erectile bodies observed shortly after the last DES injection reverted to normality in the DES P5-P15, but not in the E12-P10 and P0-P10 groups, in which MUMP cartilage and erectile body malformations persisted into adulthood, again emphasizing a "window of susceptibility" in the early neonatal period. PMID- 26810247 TI - Effects of surgery on the cancer stem cell niche. AB - Recent identification of a cancer stem cell (CSC) phenotype in solid tumors has greatly enhanced the understanding of the mechanisms responsible for cancer cell metastasis. In keeping with Pagets 'seed and soil' theory, CSCs display dependence upon stromal derived factors found within the niche in which they reside. Inflammatory mediators act as a 'fertilizer' within this niche when interacting with CSCs at the tumor-stromal interface and can potentiate the metastatic ability of CSCs. Interestingly, the same components of the pro inflammatory milieu experienced by cancer patients perioperatively are known to promote the metastagenic potential of CSCs. On the basis of this observation we discuss how surgery-induced inflammation potentiates colon CSC involvement in the metastatic process. We hypothesize that the high rates of recurrence and metastasis associated with tumor resection are potentiated by the effects of surgery-induced inflammation on CSCs. Finally we discuss potential therapeutic strategies for use in the perioperative window to protect cancer patients from the oncological effects of the pro-inflammatory milieu. PMID- 26810250 TI - Prohead RNA: a noncoding viral RNA of novel structure and function. AB - Prohead RNA (pRNA) is an essential component of the powerful Phi29-like bacteriophage DNA packaging motor. However, the specific role of this unique RNA in the Phi29 packaging motor remains unknown. This review examines pRNA as a noncoding RNA of novel structure and function. In order to highlight the reasons for exploring the structure and function of pRNA, we (1) provide an overview of Phi29-like bacteriophage and the Phi29 DNA packaging motor, including putative motor mechanisms and structures of its component parts; (2) discuss pRNA structure and possible roles for pRNA in the Phi29 packaging motor; (3) summarize pRNA self-assembly; and (4) describe the prospective therapeutic applications of pRNA. Many questions remain to be answered in order to connect what is currently known about pRNA structure to its novel function in the Phi29 packaging motor. The knowledge gained from studying the structure, function, and sequence variation in pRNA will help develop tools to better navigate the conformational landscapes of RNA. WIREs RNA 2016, 7:428-437. doi: 10.1002/wrna.1330 For further resources related to this article, please visit the WIREs website. PMID- 26810251 TI - A Web-Based Intervention to Encourage Walking (StepWise): Pilot Randomized Controlled Trial. AB - BACKGROUND: Despite Internet-based interventions that incorporate pedometers with appropriate goal-setting processes and other theoretically-based behavior change strategies being proposed as a means of increasing walking behavior, few have incorporated all of these key features or assessed maintenance of behavior change. OBJECTIVE: The objective of our study was to investigate the effect of a 12-week pedometer step goal walking program individually tailored to baseline step counts, combined with an interactive support website for step counts, health parameters and motivation over 12 and 24 weeks. METHODS: Low active participants (mean [SD] 46.2 [11.2] years) were randomly assigned to the Stepwise (SW) intervention group (n=49) or a comparison (CP) group (n=48). SW received a pedometer, step goal walking program and access to the SW website (containing interactive self-monitoring and goal feedback tools, motivational messages and action and coping planning strategies). CP received a pedometer and locally available physical activity information. Step counts, BMI, resting heart rate, blood pressure and glucose, cholesterol and triglyceride levels, psychological well-being, perceived health, self-efficacy and self-determined motivation were measured at baseline, 12 and 24 weeks. RESULTS: Linear mixed model analysis found that both groups' step counts increased from baseline to week 12 (beta = 11,002, CI 5739-16,266, P<.001) and 24 (beta = 6810, CI 1190-12,431; P=.02). Group step counts were significantly different at week 24 with SW taking 8939 (CI 274-17604, P=.04) more steps compared to CP. Compared to baseline, both groups had improved triglyceride levels (0.14 mmol/L, CI -0.25 to -0.02, P=.02) at week 12, decreased diastolic blood pressure (4.22 mmHg, CI -6.73 to -1.72) at weeks 12 and 24 (3.17 mmHg, CI -5.55 to -0.78), improved positive (beta = .21, CI 0.03-0.38, P=.02) and negative affect (beta = -.15, CI -0.28 to -0.03, P=.02) at week 12, and perceived health at week 12 (beta = 6.37, CI 2.10-10.65, P=.004) and 24 (beta = 8.52, CI 3.98-13.06, P<.001). Total cholesterol increased at week 12 (0.26 mmol/L, CI 0.099-0.423, P=.006) and week 24 (0.38 mmol/L, CI 0.20-0.56, P<.001). Repeated measures ANOVA found motivation for walking improved from baseline with higher task self-efficacy (P<.001, eta(2) = .13) and autonomous motivation (P<.001, eta(2)=.14) at weeks 12 and 24 and decreased controlled motivation (P=.004, eta(2)=.08) at week 24. CONCLUSIONS: Both groups had similar improvements in step counts and physical and psychological health after 12 weeks but only the SW group successfully maintained the increased step-counts 24 weeks post-intervention. This suggests the step-goal based walking program combined with Internet-based behavior change tools were important for sustained behavior change. PMID- 26810252 TI - Worldwide prevalence of hypospadias. AB - INTRODUCTION: Hypospadias is a common congenital malformation. Surgical repair and management of the long-term consequences require a substantial amount of socioeconomic resources. It is generally accepted that genetic and environmental factors play a major role in the etiology of hypospadias. There have been contradictory reports on rising hypospadias rates, and regional and ethnical differences. The exact prevalence of hypospadias is of major interest for healthcare providers, clinical medicine, and research. OBJECTIVE: To review the literature regarding the worldwide prevalence of hypospadias. STUDY DESIGN: Pubmed, EMBASE and Google were systematically screened for: hypospadias, congenital malformation, anomaly, incidence, prevalence, and epidemiology. Exclusion criteria were surgical and risk-factor studies. To give an additional comprehensive overview, prevalence data were harvested from the Annual Report of the International Clearinghouse Centre for Birth Defects Surveillance and Research. Prevalence was reported as per 10,000 live births. RESULTS: Data were available from 1910 to 2013. The median study period was 9 years (range: 1-36 years). Approximately 90,255,200 births have been screened in all studies. The mean prevalence were: Europe 19.9 (range: 1-464), North America 34.2 (6-129.8), South America 5.2 (2.8-110), Asia 0.6-69, Africa 5.9 (1.9-110), and Australia 17.1-34.8. There were major geographical, regional, and ethnical differences, with an extreme heterogeneity of published studies. Numerous studies showed an increasing prevalence; on the other hand, there were a lot of contradictory data on the prevalence of hypospadias. The summary table shows contradictory data from the five largest international studies available. DISCUSSION: There was huge literature available on the prevalence of hypospadias. Most data derived from Europe and North America. Many methodological factors influenced the calculation of an accurate prevalence, and even more of the true changes in prevalence over time (no generally accepted and standardized definition of hypospadias, different monitoring systems, unclear efficiency of notification and data ascertainment, etc.). There was wide variation of prevalence according to countries and ethnicity, and there were conflicting data on the recent trends of prevalence. Moreover, there weren't any epidemiologic data available from many parts of the world. CONCLUSION: True prevalence of hypospadias and trends were difficult to estimate. For the future, to be able to assess the true prevalence of hypospadias and changes in prevalence collaboration of national and international prospective registers is recommended. PMID- 26810253 TI - Enzymatic synthesis of ligand-bearing DNAs for metal-mediated base pairing utilising a template-independent polymerase. AB - We have developed a novel method to synthesise artificial ligand-bearing DNAs utilising a template-independent DNA polymerase. Hydroxypyridone ligand-bearing nucleotides () were successively appended to DNA primers by the enzyme. The resulting strands, tailed with nucleotides, formed Cu(II)-mediated metallo-DNA duplexes through the formation of metal-mediated artificial base pairs (H-Cu(II) H). PMID- 26810254 TI - Net benefit approaches to the evaluation of prediction models, molecular markers, and diagnostic tests. PMID- 26810255 TI - Regioselective Synthesis of Pyrazolo[3,4-D]Pyrimidine Based Carbocyclic Nucleosides as Possible Antiviral Agent. AB - Carbocyclic nucleosides are considered as nucleoside mimetic having high therapeutic potentials, however diverse exploration is still limited due to their synthetic difficulties. The major challenges are associated with the preparation of new base and carbocyclic sugar key intermediates. The modified base may provide conformational advantage to achieve better nucleoside mimetics and may also help in increasing the drug-like properties. In this manuscript, we report the use of acetamidine hydrochloride to synthesize 6-methyl-4-amino-pyrazolo[3,4 d]pyrimidine base and regioselective synthesis of six new carbocyclic nucleosides (6a-f) for antiviral evaluation. Theoretical investigations were carried out on the basis of thermodynamic and kinetic stability using MM based energy optimizations and QM based transition state search for the significant regioselectivity, which was further experimentally analyzed by NOE and UV spectroscopy. PMID- 26810257 TI - Sleep changes in smokers before, during and 3 months after nicotine withdrawal. PMID- 26810256 TI - Immune persistence after hepatitis B vaccination in infancy - Fact or fancy? AB - The hepatitis B vaccine has been introduced for more than 3 decades. In Hong Kong, excellent vaccine coverage through an efficient public health care system, together with supplemental programmes and easy availability of the vaccine, meant that most young pregnant women, and university students at entrance, should have been protected. Yet significant correlations in the prevalence of HBV infection with age were found in these groups of subjects, increasing from low to high endemicity rates from late teenage to the early twenties. This can only be attributed to vaccine failure, and there is cumulating evidence that several factors are involved, including the failure to respond to a primary series of hepatitis B vaccination in infancy, the waning of antibody titer with age, and loss of anamnestic response in a significant portion of the vaccinees. The duration of protection conferred by hepatitis B vaccination in infancy should be re-examined and remedial measures undertaken if its long term protection is found to be insufficient. Otherwise, the efforts to control HBV infection, especially in high endemicity regions, with universal vaccination in infancy would be rendered futile. PMID- 26810259 TI - Inhibition of cancer cell invasion by new ((3,4-dihydroxy benzylidene)hydrazinyl)pyridine-3-sulfonamide analogs. AB - Rab GTPases regulate various types of intracellular membrane trafficking in all eukaryotes. Since Rab27a and its multiple effectors are involved in exocytosis of lysosome-related organelles and play a major role in malignancy, compounds targeting Rab27a could be likely used to inhibit invasive growth and tumor metastasis. Thus, we designed and synthesized several compounds based on the previously reported Rab27a-targeting synthetic compounds identified by virtual screening, and investigated their anti-metastatic effects in MDA-MB231 and A375 cells. Among the synthesized compounds, (E)-N-(3-chlorophenyl)-6-(2-(3,4 dihydroxy benzylidene)hydrazinyl)pyridine-3-sulfonamide (3d) and (E)-N-benzyl-6 (2-(3,4-dihydroxy benzylidene)hydrazinyl)-N-methylpyridine-3-sulfonamide (3f) significantly inhibited the invasiveness of both tumor cell lines. Compounds 3d and 3f also decreased the levels of signature extracellular matrix marker proteins (fibronectin, collagen, and alpha-smooth muscle actin) and representative mesenchymal cell markers (N-cadherin and vimentin). Taken together, our results suggest that novel sulfonamide analogs have anti-metastatic activity in breast and melanoma cancer cell lines and may be used as therapeutic agents to treat malignant cancer. PMID- 26810260 TI - Discovery of highly selective CRAF inhibitors, 3-carboxamido-2H-indazole-6 arylamide: In silico FBLD design, synthesis and evaluation. AB - The recent success of vemurafenib shows the importance of selective BRAF V600E inhibition in melanoma. However, paradoxical activation by structurally diverse ATP-competitive RAF kinase inhibitors strongly suggests that selective CRAF inhibitors, not BRAF inhibitors, would be ideal for some Ras mutation cancer treatment. In this respect, we approached designing selective CRAF inhibitors starting from in silico fragment screening and synthesized a 3-carboxamido-2H indazole-6-arylamide scaffold. Most of the compounds showed potent antiproliferative activity against the WM3629 melanoma cell line and the most promising compound, compound 10d, was found to be a potent and selective CRAF inhibitor with an IC50 value of 38.6 nM, which shows greater than 270-fold selectivity over BRAF kinase (9.45 MUM). PMID- 26810261 TI - Design and synthesis of fluorescent and biotin tagged probes for the study of molecular actions of FAF1 inhibitor. AB - To study the molecular action of ischemic Fas-mediated cell death inhibitor, we prepared fluorescent-tagged and biotin-tagged probes of the potent inhibitor, KR 33494, of ischemic cell death. We used the molecular modeling technique to find the proper position for attaching those probes with minimum interference in the binding process of probes with Fas-mediated cell death target, FAF1. PMID- 26810262 TI - Structure-activity relationship study of a series of novel oxazolidinone derivatives as IL-6 signaling blockers. AB - A series of oxazolidinone and indole derivatives were synthesized and evaluated as IL-6 signaling blockers by measuring the effects of these compounds on IL-6 induced luciferase expression in human hepatocarcinoma HepG2 cells transfected with p-STAT3-Luc. Among different compounds screened, compound 4d was emerged as the most potent IL-6 signaling blockers with IC50 value of 5.9 MUM which was much better than (+)-Madindoline A (IC50=21 MUM), a known inhibitor of IL-6. PMID- 26810263 TI - Semisynthesis of new aphidicolin derivatives with high activity against Trypanosoma cruzi. AB - Chagas disease continues to be a difficult disease to eradicate, largely because of the widespread populations it affects as well as the highly toxic effects of current therapies. Thus, the exploration of innovative scaffolds, ideally with distinct mechanisms of action, is urgently needed. The natural product aphidicolin and its effects on cell cycle division have been widely studied; it is a potent inhibitor of parasitic cells. In the present study, we report for the first time the semisynthesis of a series of aphidicolin derivatives, their unique structural features, and demonstration of their activity against Trypanosoma cruzi cells. Two demonstrated high potency and selectivity against parasitic amastigote cells, and thus show promise as new leads for Chagas disease treatment. PMID- 26810264 TI - Synthesis and antibacterial activity of pyridinium-tailored 2,5-substituted-1,3,4 oxadiazole thioether/sulfoxide/sulfone derivatives. AB - By introducing the pyridinium group into 2,5-substituted-1,3,4-oxadiazole, a series of pyridinium-tailored 2,5-substituted-1,3,4-oxadiazole thioether/sulfoxide/sulfone derivatives were obtained, and their antibacterial activities were evaluated via turbidimeter test in vitro. The bioassays reveal that most of the target compounds exhibit better inhibition activities against pathogen Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri than positive controls bismerthiazol (CK1) or thiodiazole copper (CK2). Among them, I-8, I-10, I-12, II-10, II-12, III-10, and III-12 exert excellent inhibition activities against the three pathogenic bacteria with the half-maximal effective concentration (EC50) values ranging from 0.54 to 12.14 MUg/mL. Our results demonstrate that pyridinium-tailored 1,3,4-oxadiazole thioether/sulfoxide/sulfone derivatives can serve as potential alternative bactericides for the management of plant bacterial diseases. PMID- 26810265 TI - Identification of new SUMO activating enzyme 1 inhibitors using virtual screening and scaffold hopping. AB - Sumoylation involves the enzymatic conjugation of small ubiquitin-like modifier (SUMO) protein to their substrate proteins. Sumoylation is not only crucial for maintaining normal cellular physiology but also implicated in the development of several diseases including cancer. SUMO E1, the first protein in sumoylation pathway is of particular significance due to its confirmed role in tumorogenesis. However, notwithstanding its role as potential drug target, only a few small molecule inhibitors of SUMO E1 have been identified. Here, we report the identification of pyrazole and thiazole urea containing compounds as inhibitors of SUMO E1. We have utilized 3D-shape matching, electrostatic potential similarity evaluations and molecular docking to scaffold hop from previously known aryl urea scaffold with SUMO E1 activity to thiazole and pyrazole urea based scaffolds. These two classes of compounds were found to have moderate SUMO E1 inhibitory activity and can be used as starting points for the development of highly potent lead compounds against cancer. PMID- 26810266 TI - Uncovering Neuroanatomical Networks Responsible for Abnormal Eating Behavior in Frontotemporal Dementia. PMID- 26810267 TI - Neonatal Baclofen Withdrawal: A Case Report of an Infant Presenting With Severe Feeding Difficulties. PMID- 26810268 TI - Forefoot ulcer risk is associated with foot type in patients with diabetes and neuropathy. AB - AIMS: To stratify the ulceration risk according to the foot morphology in people with diabetes and a history of forefoot neuropathic ulceration. METHODS: A cross sectional study was performed on 139 neuropathic individuals with diabetes and previous forefoot ulcers between January 2012 and February 2014. Foot position of the participants was evaluated by using the foot-posture index. A multivariate analysis adjusted for confounding variables was performed with the ulceration risk factors that were found in the univariate analysis. RESULTS: Two hundred and fifty-eight feet were analysed, 104 (40.3%) feet had a history of ulceration on the forefoot and 154 (59.7%) feet had no previous ulceration. Two positive tests of neuropathy (p<0.001; CI[1.961-6.249] OR 3.500), presence of deformities (p=0.043; CI[1.020-3.599] OR 1.916) and foot type (p=0.039) showed an association with ulceration risk in multivariate analyses. Pronated feet showed a higher risk of ulceration than supinated feet (p=0.011; CI[1.253-5.708] OR 2.675), while significant differences between neutral and supinated feet were not found (p=0.221; CI[0.719-2.753] OR 1.476). CONCLUSIONS: A pronated foot has a higher risk of ulceration on the forefoot in neuropathic people with deformities and diabetes mellitus. Foot type should be evaluated in people at risk of ulceration. PMID- 26810269 TI - Glycemic excursions are positively associated with changes in duration of asymptomatic hypoglycemia after treatment intensification in patients with type 2 diabetes. AB - AIM: The aim of this study was to examine the association between glycemic excursions and duration of hypoglycemia after treatment intensification in patients with type 2 diabetes (T2D). METHODS: Patients with T2D on oral anti diabetes drug (OAD) with glycated hemoglobin (HbA1c) of 7.0-11.0% were switched to metformin monotherapy (500 mg thrice daily) for 8 weeks, followed by randomization to either glibenclamide or acarbose as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring (CGM) before randomization and at the end of study. Hypoglycemia was defined as sensor glucose level of less than 60 mg/dl in two or more consecutive readings from CGM. RESULTS: A total of 50 patients (mean age 53.5 +/- 8.2 years, male 48%, mean baseline HbA1c 8.4 +/- 1.2%) were analyzed. Duration of hypoglycemia significantly increased after treatment with glibenclamide (from 5.5 +/- 13.8 to 18.8 +/- 35.8 min/day, p=0.041), but not with acarbose (from 2.9 +/- 10.9 to 14.7 +/- 41.9 min/day, p=0.114). Post treatment MAGE was positively associated with change from baseline in duration of hypoglycemia after treatment with either glibenclamide (beta coefficient 0.345, p=0.036) or acarbose (beta coefficient 0.674, p=0.046). The association remained significant after multivariate adjustment (p<0.05 for all models). CONCLUSIONS: Post treatment glycemic excursions are associated with changes in duration of hypoglycemia after treatment intensification with OAD in patients with T2D. Glycemic excursions should be an important treatment target for T2D to reduce the risk of hypoglycemia. PMID- 26810270 TI - The impact of initial antidiabetic agent and use of monitoring agents on prescription costs in newly treated type 2 diabetes: A retrospective cohort analysis. AB - AIMS: To measure the costs associated with the use of antidiabetic agents, monitoring materials and cardiovascular disease (CVD) agents in the management of newly treated type 2 diabetes, and to investigate the factors associated with these costs. METHODS: A population-based retrospective cohort study was conducted using the Irish national pharmacy claims database. Newly treated patients were identified for 2012 and followed for one year post treatment initiation. Factors associated with costs were assessed using a generalised linear model with gamma family and log-link function. Cost ratios (CR) and 95% CIs were used to determine the contributors of prescription costs. Adjusted odd ratios (OR) and 95% CIs were used to investigate factors associated with high frequency self-monitoring of blood glucose (SMBG). RESULTS: Mean prescription costs for the 12,941 subjects was ?871, while total costs were ?11 million. CVD agents accounted for 58% of total costs; 22% of costs were for SMBG; antidiabetic agents accounted for 17% of costs. SMBG resulted in costs that were 80% higher than those without, CR 1.80 (95% CI 1.76-1.84). No significant differences were observed between initiation on metformin or sulphonylureas and high frequency SMBG (OR 1.01 95% CI 0.97-1.04 vs reference). Initiation on newer antidiabetic agents was a significant positive predictors of prescription costs (CR 2.36 95% CI 2.21-2.51 vs metformin). CONCLUSIONS: Type of initial antidiabetic agent, and SMBG were significant predictors of prescription costs. SMBG represent a major proportion of total costs; however, its use in combination with antidiabetic agents that do not cause hypoglycaemia is questionable. PMID- 26810271 TI - Licensing regulations for diabetes and driving--Two sides of the same coin? PMID- 26810272 TI - Pregnancy outcome in pregnancies complicated with gestational diabetes mellitus and late preterm birth. AB - AIM: To assess pregnancy outcome among women with gestational diabetes mellitus (GDM) delivering at the late preterm period. METHODS: Retrospective observational cohort of all women with GDM who delivered a singleton fetus at the late preterm birth period (34+0/7 to 36+6/7 weeks of gestation). The study group included all women diagnosed with GDM and were compared to a control group of women delivering at the same gestational age period but without known GDM. RESULTS: 1849 women were included in the study, of whom 132 (7.1%) were diagnosed with GDM and 1717 (92.9%) were not. Women with GDM had a lower rate of spontaneous vaginal delivery (45.5% vs. 62.9%, p<0.001) and a higher rate of cesarean delivery (50.8% vs. 31.8%, p<0.001). GDM diagnosis incurs an adjusted ratio of 1.82 for cesarean delivery (95% CI 1.24-2.66, p=0.002). Neonates of mothers with GDM had significant higher mean birth weight and birth weight percentile, including higher rate of large-for-gestational age newborns. There were no differences in mortality or other parameters for neonatal morbidity. CONCLUSION: according to our data, late preterm occurring in women with GDM does not confer an increased risk for neonatal complications. PMID- 26810273 TI - The association of obstructive sleep apnea (OSA) and nocturnal hypoxemia with the development of abnormal HbA1c in a population cohort of men without diabetes. AB - AIM: To examine the relationship between indices of undiagnosed OSA and the development of abnormal glycaemic control in community-dwelling men free of diabetes. METHODS: The Men, Androgens, Inflammation, Lifestyle, Environment, and Stress (MAILES) Study is a population-based cohort study in Adelaide, South Australia. Clinic visits at baseline (2002-06) and follow-up (2007-10) identified abnormal glycaemic metabolism [HbA1c 6.0 to <6.5% (42 to <48mmol/mol)] in men without diabetes. At follow-up (2010-11), n=837 underwent assessment of OSA by full in-home unattended polysomnography (Embletta X100). RESULTS: Development of abnormal glycaemic metabolism over 4-6 years (n=103 "incident" cases, 17.0%) showed adjusted associations [odds ratio (95% CI)] with the 1st [1.7 (0.8-3.8)], 2nd [2.4 (1.1-4.9)], and 3rd [2.3 (1.1-4.8)] quartiles of mean oxygen saturation (SaO2) compared to the highest quartile. Prevalent abnormal glycaemic metabolism (n=140, 20.8%) was independently associated with the third and fourth quartiles of percentage of sleep time with oxygen saturation <90% and lowest quartile of mean SaO2. Linear regression analysis showed a significant reduction in HbA1c [unstandardized B, 95% CI: -0.02 (-0.04, -0.002), p=0.034] per percentage point increase in mean SaO2. OSA as measured by the apnea-hypopnea index showed no adjusted relationship with abnormal glycaemic metabolism. CONCLUSIONS: Development of abnormal glycaemic metabolism was associated with nocturnal hypoxemia. Improved management of OSA and glycaemic control may occur if patients presenting with one abnormality are assessed for the other. PMID- 26810274 TI - c-Abl contributes to glucose-promoted apoptosis via p53 signaling pathway in podocytes. AB - AIM: To investigate the role of the non-receptor tyrosine kinase c-Abl in high glucose-induced podocyte injury and its possible signal transduction pathway. METHODS: Sixteen C57BL/6 mice were randomly assigned to a group with diabetes and a normal control group. Subsequently, differentiated mouse podocytes were exposed to high-glucose conditions, and podocyte apoptosis was then assessed by flow cytometry and Hoechst 33258 staining. Western blot and immunofluorescence assay were used to measure c-Abl expression. Co-immunoprecipitation assay was used and c-Abl siRNA was applied to evaluate the interaction between c-Abl and p53. RESULTS: High glucose promotes podocyte apoptosis. The c-Abl expression in podocytes was increased after exposure to high glucose, stimulating the p53 signaling pathway. Conversely, treatment with c-Abl siRNA restored high glucose promoted podocyte apoptosis and resulted in the reduction of p53 expression. CONCLUSION: c-Abl contributes to high glucose-induced podocyte apoptosis via p53 signaling pathway. PMID- 26810275 TI - Upholding Family-Centered Care in the Face of High-Consequence Pathogens- Thinking Inside the Room--Reply. PMID- 26810276 TI - Vedolizumab in the treatment of Crohn's disease. AB - Vedolizumab, a recent addition to the therapeutic armamentarium in Crohn's disease, is promising in efficacy, durability of remission and safety. It is the first gut selective biologic treatment, acting by targeting alpha4beta7-integrin, a receptor expressed on activated lymphocytes and binding to MAdCAM1, a cell adhesion molecule selectively expressed in the circulatory system of the digestive tract, preventing trafficking of lymphocytes to the gut. The pivotal GEMINI studies have demonstrated the efficacy and safety of vedolizumab in achieving clinical response and clinical remission in patients with moderately to severely active CD who are naive or have previously failed therapy with TNF antagonists, immunomodulators or dependent on steroids. Vedolizumab had a favorable safety profile and specifically showed no evidence of PML, reactivation of latent TB or hepatitis B. Overall, the number of malignancies in the clinical trials was small; however, long-term exposure was limited. Vedolizumab can be given as a first-line therapy or following treatment failure, and was tolerated as part of combination therapy. More medications with similar and novel therapeutic mechanisms are anticipated in the coming years. PMID- 26810277 TI - Innovative High Gas Pressure Microscopy Chamber Designed for Biological Cell Observation. AB - An original high-pressure microscopy chamber has been designed for real-time visualization of biological cell growth during high isostatic (gas or liquid) pressure treatments up to 200 MPa. This new system is highly flexible allowing cell visualization under a wide range of pressure levels as the thickness and the material of the observation window can be easily adapted. Moreover, the design of the observation area allows different microscope objectives to be used as close as possible to the observation window. This chamber can also be temperature controlled. In this study, the resistance and optical properties of this new high pressure chamber have been tested and characterized. The use of this new chamber was illustrated by a real-time study of the growth of two different yeast strains - Saccharomyces cerevisiae and Candida viswanathii - under high isostatic gas pressure (30 or 20 MPa, respectively). Using image analysis software, we determined the evolution of the area of colonies as a function of time, and thus calculated colony expansion rates. PMID- 26810279 TI - The prevalence of airway problems in children with Down's syndrome. AB - AIM: Airway disorders are common in children with Down's syndrome. We report the findings on airway endoscopy in a birth cohort of children from a well-defined geographical area, in order to estimate true population prevalence of airway problems in children with Down's syndrome. METHOD: Retrospective case note review over a 20-year period between 1993 and 2013 for all children in Greater Glasgow born with Down's syndrome, identified through the hearing surveillance programme. All children undergoing airway endoscopy under general anaesthesia for investigation of potential airway symptoms (stridor, hoarseness, recurrent croup and difficulties with intubation/extubation) were studied in detail to identify the number with laryngeal, tracheal or bronchial pathology. RESULTS: All 239 children (F:M=1.15:1) were reviewed. Of these, 39 (16.3%) underwent microlaryngoscopy-bronchoscopy under general anaesthesia for airway symptoms. The main presentations were stridor (9), extubation problems (12) and exacerbations of recurrent croup (7). Thirty-three were found to have at least one airway diagnosis (13.8%) including trachaeobronchomalacia (17), laryngeal cleft (2), laryngomalacia (2), tracheal compression (2), vocal cord paralysis (1), acquired tracheal stenosis (2) and symptomatic subglottic stenosis (14). CONCLUSION: Laryngo-tracheo-bronchial pathology is much more common in children with Down's syndrome than in the general population, particularly subglottic stenosis and tracheal problems. PMID- 26810280 TI - The validation of an algorithm for the management of paediatric cervical lymphadenopathy. PMID- 26810281 TI - Phenotype in a patient with p.D50N mutation in GJB2 gene resemble both KID and Clouston syndromes. AB - Keratitis-ichthyosis-deafness (KID) syndrome (OMIM 148210) is a rare ectodermal dysplasia syndrome characterized by vascularizing keratitis, congenital profound sensorineural hearing loss, and progressive erythrokeratoderma. We have found a 148G-A transition in the GJB2 gene, resulting in an asp50-to-asn (D50N) substitution in a girl with congenital deafness. This finding allowed us to diagnose a KID syndrome. But clinical features were uncommon because of a mild skin manifestation, lack of keratitis and unusual appearance resembling Clouston syndrome. Molecular genetic tests showed that it was de novo mutation because parents have normal genotype. Several autosomal dominant mutations in the GJB2 gene (sonnexin 26) now established to underlie many of the affected cases, with the majority of patients harboring the p.D50N mutation. Skin disease-associated mutation of connexin proteins can cause functional disturbances in gap junction intercellular conductance. It is likely that multiple disease mechanisms are involved across the wide spectrum of hereditary diseases relating to connexin proteins. The clinical data may provide additional insights into the dysregulation mechanisms of mutations result in the disease. PMID- 26810282 TI - Decreased level of osteopontin in children with allergic rhinitis during sublingual immunotherapy. AB - OBJECTIVE: Sublingual immunotherapy (SLIT) is proven to be very effective in the treatment of allergic rhinitis (AR), but its regulatory mechanism and biomarkers for predicting efficacy are still unknown. Osteopontin (OPN), as a recently described Th2 inflammation related protein, plays key role in the pathogenesis of AR. The aim of this study was to identify the expression and role of OPN during SLIT in children. METHODS: Fifty house dust mite (HDM)-sensitized children with AR were enrolled in this study. AR children received HDM allergen extract or placebo for SLIT. Serum of different time points during treatment was collected and used for enzyme-linked immuno sorbent assay (ELISA) of OPN and related cytokines, respectively. Peripheral blood mononuclear cells from children after SLIT or placebo treatment were collected and stimulated with HDM with or without OPN/anti-OPN after one year's treatment. RESULTS: Our results showed that expression of OPN protein was decreased after one year's therapy. The decreased OPN expression was positively related to decreased Th2 cytokines and negatively related to enhanced IL-10 and TGF-beta expression. In vitro experiments confirmed that children received SLIT treatment showed decreased production of Th2 cytokines by PBMCs after HDM stimulation. CONCLUSION: During SLIT, decreased OPN expression was related to low Th2 cytokine expression and enhanced IL-10 and TGF beta expression. High serum OPN expression predicts poor treatment efficacy. OPN may be used as a biomarker for SLIT treatment. PMID- 26810283 TI - ABR thresholds in infants born with CLP and OME and infants with OME. AB - OBJECTIVES: The aim of this study was to investigate and compare auditory brainstem response (ABR) thresholds related to otitis media with effusion (OME) in infants with and without cleft palate and/or lip (CP+/-L). METHODS: Forty seven infants with CP+/-L and 67 infants with OME participated in the study. Hearing thresholds of ears of infants with OME were compared between groups and within the group with CP+/-L. RESULTS: Infants with CP+/-L and OME presented with similar hearing thresholds as infants with OME and not CP+/-L. Within the cleft group, infants with isolated cleft palate and OME demonstrated significantly higher hearing thresholds than infants with unilateral cleft lip and palate and OME. CONCLUSION: A high prevalence of infants with CP+/-L present with OME early in life. Hearing thresholds of these infants are similar to infants without CP+/ L, but with OME. The ear status and hearing thresholds of infants with CP+/-L needs to be monitored to be able to provide the best access to hearing in order to fully allow speech and language development. PMID- 26810284 TI - Pediatric epidermoid cysts masquerading as ranulas: A case series. AB - Pediatric neck masses represent a variety of differential diagnoses. A common pathology in pediatric cystic neck tumors include ranulas, mucus retention cysts due to salivary gland obstruction. Epidermoid cysts are lesions infrequently encountered in the pediatric population and may appear similarly to ranulas on computed tomography imaging. MRI more easily differentiates these masses, and should therefore be the preferred imaging modality. Due to their distinct intraoperative management, ranulas and epidermoid cysts should be distinguished preoperatively through proper workup. PMID- 26810285 TI - Factors related to persisting perforations after ventilation tube insertion. AB - OBJECTIVE: Over a million ventilation tubes are placed annually in the United States, making this one of the most commonly performed procedures in the field of medicine. Certain factors increase the risk of persistent tympanic membrane perforation following the extrusion of short term ventilation tubes. Persistent perforations may fail to heal on their own, necessitating surgical closure to avoid conductive hearing loss. It is important to detect factors that may predict children who are at increased risk for persistent perforations. METHODS, OUTCOMES DATA AND STATISTICAL ANALYSIS: This study was a retrospective chart review that involved 757 patients between 2003 and 2008. The patients studied were within the age of 2 months-17 years, and all had short term tubes placed. The chart data also included demographic information, comorbidities, and information related to tube insertion and follow-up care. Chi-square, t-test, and multivariate logistic regression were conducted to compare variables between patients with perforations and those without. RESULTS: Data from 757 patients was analyzed, showing that perforation rate is associated with rhinorrhea, operative tube removal, aural polyps, and otorrhea (OR 1.72, 8.16, 4.69, and 1.72 respectively). The absence of otorrhea decreased the likelihood of TM perforations and no significant differences were found in gender, total number of sets of tubes, type of tube, use of nasal steroids, adenoidectomy, or nasal congestion. CONCLUSION: Our findings suggest that children with rhinorrhea, otorrhea, aural polyps, or prolonged intubation requiring operative tube removal should be identified clinically as children at risk of persisting perforation. PMID- 26810286 TI - Expression of CXCL4 and aquaporin 3 and 10 mRNAs in patients with otitis media with effusion. AB - PURPOSE: Bacterial infections in children with underdeveloped Eustachian tubes are a major cause of otitis media with effusion (OEM), and persistent effusion in the middle ear in these patients is a major cause of surgical intervention. CXCL4 is associated with bacterial infection, and aquaporins 3 and 10 are associated with water metabolism. This study assessed the expression of mRNAs encoding CXCL 4 and aquaporins 3 and 10 in the effusion of pediatric OME patients, and the association of this expression with clinical manifestations. METHODS: Levels of CXCL4 and aquaporin 3 and 10 mRNA were assayed by real-time RT-PCR in the middle ear effusion of 38 pediatric patients with OME requiring ventilation tube insertion. The relationships of these mRNA levels with the presence of bacteria; concomitant diseases such as allergic rhinitis, sinusitis, and adenoid disease; recurrence of OME; and number of ventilation tube insertions were evaluated. RESULTS: CXCL4 and aquaporin 3 and 10 mRNAs were expressed in middle ear effusion of all OME patients. CXCL-4 mRNA levels were significantly lower when bacteria were present and in patients with concomitant diseases (p<0.05 each). Levels of all three mRNAs were unrelated to OME recurrence or number of ventilation tube insertions (p>0.05 each). The levels of CXCL4 and aquaporin 10 mRNAs were significantly correlated (p<0.05). CONCLUSION: Expression of CXCL4 and aquaporin 3 and 10 mRNAs in middle ear effusion is associated with the pathophysiology of OME. CXCL4 mRNA levels are significantly lower in patients with than without concomitant diseases or bacterial infections. PMID- 26810287 TI - Dystrophic calcification: A rare pediatric parotid mass. AB - Dystrophic calcification, the ectopic deposition of calcium in previously damaged or inflamed tissues, is an uncommon finding in the head and neck. Only a few cases have been reported in the parotidomasseteric region, and all of them have been located within and adjacent to the masseter. We present a case of dystrophic calcification occurring entirely within the parotid gland in a 7-year-old girl without apparent inciting inflammation, infection, or trauma. Our patient's presentation highlights the diagnostic challenge associated with parotid masses in the pediatric population. To our knowledge, this is the first reported case of dystrophic calcification occurring entirely within the parotid gland in a child. PMID- 26810288 TI - Mannose binding lectin codon 54 polymorphism and susceptibility to recurrent respiratory tract infections in children: A meta-analysis. AB - BACKGROUND: There have been studies focused on mannose binding lectin (MBL) polymorphism and susceptibility to recurrent respiratory tract infections (RRTI) with inconclusive results. This present study is a meta-analysis of possible MBL and RRTI association in children. METHODS: A literature search was performed using Medline and PubMed and abstracts were reviewed for relevance. Any study was considered to be eligible for inclusion if it met the following criteria: the MBL gene polymorphism at codon 54 was determined, the outcome was recurrent respiratory tract infection in children and there were at least two comparison groups. The odds ratios(OR) of the genetic MBL polymorphisms were combined and calculated, and the forest plots of the OR value distributions were drawn. Chi squared testing of heterogeneity was done (p<0.001). RESULTS: Five eligible studies were included in the study. There has been heterogeneity between the studies (p=0.001). Our results did not show any association between MBL genotypes AA, BB, AB, alleles A and B and RRTI. CONCLUSIONS: Our meta-analysis of accessible, published data has demonstrated no statistically significant association between MBL2 genotype and recurrent respiratory tract infection in children. Summary of the article's main point Here are discrepancies regarding the importance of MBL polymorphism and its impact on recurrent respiratory tract infections. Our meta analysis did not find statistically significant association between MBL codon 54 polymorphism and recurrent respiratory tract infection in children. PMID- 26810289 TI - Changes in body composition and growth pattern after adenotonsillectomy in prepubertal children. AB - OBJECTIVE: Adenotonsillar hypertrophy and chronic tonsillitis are associated with growth interruption during childhood, while adenotonsillectomy has been associated with growth improvement and increased body mass index (BMI). However, no reported study has investigated the effect of adenotonsillectomy on the proportion of body muscle and fat mass. The aim of this prospective study was to evaluate the effect of adenoidectomy and adenotonsillectomy on body muscle and fat composition in prepubertal children. METHODS: Thirty prepubertal children (22 boys, 8 girls; 3-9 years of age) were followed up for 6 months after adenoidectomy or adenotonsillectomy. Twenty-eight age-matched healthy children (12 boys, 16 girls) were followed for the same period, as controls. Data on dietary habits and physical activity were obtained from parent-completed questionnaires at baseline and 6 months. Height and weight z-scores, the amount and percentage of body fat and muscle mass, BMI z-scores, relative BMI and basal metabolic rate were evaluated before and 6 months after surgery with bioelectrical impedance analysis. RESULTS: After 6 months, body muscle mass and basal metabolic rate scores were significantly higher than at baseline in both groups (P<0.05). The rate of increase was not different between the groups. In the study group, the relative BMI scores improved significantly (P<0.05). Increases in body fat mass, body fat percentage, height z-scores, weight z-scores and BMI z-scores were not significantly different between the groups at 6 months (P>0.05). The number of overweight and obese children did not change significantly in either group (P<0.05). CONCLUSIONS: Adenotonsillectomy led to improvement in relative BMI and promoted healthy weight gain without increased body fat percentage in prepubertal children. PMID- 26810290 TI - Myocutaneous sternocleidomastoid flap for reconstruction after the resection of a parapharyngeal heterotopic glioma in a child with cleft palate, and systematic review of parapharyngeal glial heterotopia. AB - We describe the surgery and reconstruction employed with a sternocleidomastoid myocutaneous flap for the treatment of a heterotopic glioma in a 2-year-old boy with incomplete palatal fissure who presented with dysphagia and snoring, in whom a lateral pharyngeal wall mass obstructing 60% of the airway was noted. Heterotopic gliomas are uncommonly reported in the parapharyngeal space and should be included in the differential diagnosis at this location in children. Parapharyngeal tumors present difficult diagnostic and management challenges; head and neck surgeons must be prepared not only for the resection but also for the reconstruction of these rare lesions. PMID- 26810292 TI - Congenital midline cervical cleft: A retrospective case series of 8 children. AB - OBJECTIVES: Congenital midline cervical cleft is a rare developmental abnormality of the ventral neck of unclear etiology. It consists of a midline skin defect. This study reports a case series of 8 patients with congenital midline cervical cleft. METHODS: Retrospective review chart including all children referred with congenital midline cervical cleft over 5 years in tertiary center. The study was conducted to determine the presence of associated malformations, to specify the cleft pathology, to analyze the nature of associated cysts, and to discuss surgical procedure. RESULTS: Eight patients ranged from 3 days to 5 years. Two had an associated cervical midline cyst, 3 had a significant micrognatia. Pathological observations were in favor of a branchial origin. There was no recurrence of cervical contraction after a mean follow-up of 20 months. CONCLUSION: Congenital midline cervical cleft is a rare and generally isolated congenital malformation. It does not require either extensive assessment or specific genetic. Described associated cysts might be part of the cleft and not bronchogenic or thyroglossal cysts. Early surgical excision reduces cervical contracture, but linear or Z-plasty closure is still debated. PMID- 26810291 TI - Use of symptoms and risk factors to predict acute otitis media in infants. AB - OBJECTIVES: Infants and children with upper respiratory tract infection (URI) often have concurrent acute otitis media (AOM). Young infants have fewer specific symptoms than older children. The purpose of this study was to evaluate the usefulness of symptoms and other risk factors in predicting the presence of AOM in infants. METHODS: Healthy infants, age less than four weeks, were enrolled and followed prospectively for up to age one year. Infants were scheduled for a research visit when their parents noted the onset of symptoms. At each URI visit, parents first reported the severity of symptoms. An investigator then diagnosed the presence or absence of concurrent AOM. Risk factors and symptom scores for infants with and without AOM were studied. RESULTS: Infants (N=193, mean age at first URI 3.9+/-2.5 months) experienced 360 URI episodes and 63 AOM events. Symptoms consisting of fever, earache, poor feeding, restless sleep, and irritability together (ETG-5) were statistically associated with the prediction of AOM (P=0.006). A multiple variable statistical model (J-Score) that included day care attendance, age, severity of cough and earache best predicted AOM (P<0.001), with 95% specificity. Both ETG-5 and J-score yielded relatively low sensitivity for AOM prediction. CONCLUSIONS: In infants with URI in the first year of life, severity of symptoms was significantly associated with concurrent AOM. Daycare attendance, presence and severity of earache and cough added to better correlation. These observations may have clinical application in identification of infants at risk for AOM. PMID- 26810293 TI - Congenital sternoclavicular dermoid sinus. AB - We report a case series of 8 patients, presenting with a congenital sinus in the region of the sternoclavicular joint. This rare malformation has only been reported in the Japanese dermatological literature under the name of "congenital dermoid fistula of the anterior chest region". It has to be distinguished from other congenital anomalies and requires complete excision. PMID- 26810294 TI - Frequency-specific Animal Sound Test (FAST) 4: A valid method for hearing screening. AB - OBJECTIVES: It is essential to monitor hearing status in children not only as a mandatory requirement during universal newborn hearing screening (UNHS), but also later during preschool and school-age development. The present study considers the appropriateness of the Frequency-specific Animal Sound Test (FAST4) for use in children between the ages of 2.5 and 10 years; the comparability of hearing thresholds determined using FAST4 and those measured by pure tone audiometry (PTA); and the clinical and diagnostic utility of FAST4 in a variety of pediatric settings. METHODS: 322 children aged 2.6-14.1 years and 41 adults were tested with FAST4. Four animal sounds were presented via headphones and a hearing threshold was determined for the high and low frequency range. In addition, the hearing threshold of each child was measured by PTA. RESULTS: Results were analyzed from 156 normal-hearing and hearing-impaired children, mostly above the age of 4 years. In general, FAST4 yielded hearing levels comparable with those from PTA in children and in adults. FAST4 frequently had to be halted prematurely in children under 4 years old. CONCLUSIONS: FAST4 is a strong candidate for use as an instrument for preschool hearing screening and offers several advantages over other hearing tests. FAST4 permits simple, swift and efficient determination of the hearing threshold and the test can be administered by staff without specialist training. A number of improvements have already been integrated into the successor model known as mFAST. PMID- 26810295 TI - Acute mastoiditis in children with a cochlear implant. AB - OBJECTIVES: Cochlear implantation is performed at a young age, when children are prone to acute otitis media. Acute mastoiditis is the most common complication of otitis media, but data on its management in the presence of a cochlear implant are sparse. The objective of this study was to assess the characteristics, treatment, and outcome of acute mastoiditis in children with a cochlear implant. METHODS: The medical files of all children who underwent cochlear implantation at a pediatric tertiary medical center in 2000-2014 were retrospectively reviewed. Those diagnosed with acute mastoiditis after implantation were identified, and data were collected on demographics, history, presentation, method of treatment, complications, association with untreated otitis media with effusion, and long term middle-ear sequelae. RESULTS: Of the 370 children (490 ears) who underwent cochlear implantation, 13 (3.5%) were treated for acute mastoiditis (median age at acute mastoiditis, 32 months). Nine had a pre-implantation history of chronic secretory or acute recurrent otitis media, and 5 had been previously treated with ventilation tubes. In all 9 children who had unilateral cochlear implant, the acute mastoiditis episode occurred in the implanted ear. The time from implantation to mastoiditis was 5-61 months. The same treatment protocol as for normal-hearing children was followed, with special attention to the risk of central nervous system complications. Primary treatment consisted of myringotomy with intravenous administration of wide-spectrum antibiotics. Surgical drainage was performed in 8 out of 13 patients, with (n=7) or without (n=1) ventilation tube insertion, to treat subperiosteal abscess or because of lack of symptomatic improvement. There were no cases of intracranial complications or implant involvement or need for a wider surgical approach. No middle-ear pathology was documented during the average 3.8-year follow-up. CONCLUSIONS: The relatively high rate of acute mastoiditis and subperiosteal abscess in children with a cochlear implant, predominantly involving the implanted ear, supports the suggestion that recent mastoidectomy may be a risk factor for these complications. Despite the frequent need for drainage, more extensive surgery is usually unnecessary, and recovery is complete and rapid. As infections can occur even years after cochlear implantation, children with otitis media should be closely followed, with possible re-introduction of ventilation tubes. PMID- 26810296 TI - Evaluation of the radiological criteria to diagnose large vestibular aqueduct syndrome. AB - OBJECTIVE: The main objective of the current work is to increase the sensitivity of the radiological diagnosis of the large vestibular aqueduct syndrome (LVAS). The specific aims were to compare between the two famous criteria to diagnose large vestibular aqueduct (LVA), (i.e., Valvassori and Cincinnati), to correlate between vestibular aqueduct (VA) measurements in the axial view and those in 45 degrees oblique reformate in children with LVAS, and to define radiological criteria to diagnose LVA in the 45 degrees oblique reformate. METHODS: The study group included 61 children with LVAS according to Cincinnati criteria (greater than 0.9mm at the midpoint or greater than 1.9mm at the operculum in the axial view). All participants were subjected to full Audiological evaluation and CT scanning in axial plane. The axial data were then transferred to workstation for post-processing with 3D reformatting software (Baxara 3D) in order to obtain the 45 degrees oblique reformates. VA measurements were done at 4 points: midpoint and operculum in both the axial plane and the 45 degrees oblique reformate. RESULTS: Only 81% of ears of children with LVAS (99 ears) fit Valvassori criterion (i.e., larger than 1.5mm at midpoint), while 19% (23 ears) of them were missed. There were statistically significant correlations among the diameters of the VA in the axial view (both in the midpoint and operculum) and their counterparts in the 45 degrees oblique reformate. Values equal to or greater than 1.2mm in the midpoint and 1.3mm in the operculum are proposed to be the criteria to diagnose LVA in the 45 degrees oblique reformate. Finally, no significant correlations were found between the degree of hearing loss and VA diameters at the axial or 45 degrees oblique reformate. CONCLUSION: Cincinnati criteria are more sensitive than Valvassori criterin in the diagnosis of LVAS. We recommend the application of Cincinnati criteria instead of Valvassori criteria in order not miss cases with LVAS. Measurement of VA in the 45 degrees oblique reformate is a reliable method to diagnose LVA. Criteria to diagnose LVA in the 45 degrees oblique reformate were proposed. PMID- 26810297 TI - A novel recessive truncating mutation in MYO15A causing prelingual sensorineural hearing loss. AB - Hearing loss (HL) is one of the most common human defects which affects millions of people globally. The identification of deafness-related genes or loci may facilitate basic and clinical translational research on this disorder. Here, we investigated a Chinese family with autosomal recessive non-syndromic hearing impairment. Using targeted massively parallel sequencing, we identified a novel homozygous mutation, c.3525_3526insA and p.Q1175fsX1188 (NM_016239), in exon 2 of MYO15A. Sanger sequencing confirmed that affected siblings were homozygous for the mutation, whereas both normal hearing parents were heterozygous. The mutation was absent in 96 healthy controls and public databases. The insertion leads to a frameshift and a truncated form of the protein, resulting in the pathogenic effect of hearing loss for the patients. Mutations in exon 2 of MYO15A may cause a less severe phenotype, facilitating the rapid identification of mutations in exon 2 among the 66 exons when linkage of less severe hearing loss to Deafness, Autosomal Recessive 3 (DFNB3) is detected. Our data provide additional molecular information for establishing a better genotype-phenotype understanding of DFNB3. PMID- 26810298 TI - Avoidance of a potential tracheoinnominate fistula by innominate artery re implantation in a four year old girl with tracheostomy dependence and Pfeiffer syndrome. AB - A 4 year old tracheostomy dependent girl with Pfeiffer syndrome was noted on bronchoscopy to have a pulsatile tracheostomal mass. CT chest angiography was consistent with the innominate artery crossing anterior to the trachea and superior to the sternal notch. The patient underwent reimplantation of the innominate artery via a median sternotomy approach. Tracheoinnominate fistula is a potentially devastating complication of tracheostomy. We report discovery of a near tracheoinnominate fistula in order to highlight the importance of regular interval surveillance endoscopy in tracheostomy dependent children and to discuss a preventative surgical intervention employed in prevention of this potentially devastating complication. PMID- 26810299 TI - Using ultrasound visual feedback to remediate velar fronting in preschool children: A pilot study. AB - Anecdotally, velar fronting can be difficult to remediate in some children. This pilot study examined the use of ultrasound visual feedback in remediating velar fronting in typically developing children. A single-case, multiple-baseline across-subjects experimental design was used to examine acquisition, retention and generalisation of velar treatment targets. Two otherwise typically developing children (P1, aged 4;0; P3, aged 4;11) completed the study. The productions of /k/ and /g/ at syllable level were targeted during treatment. P1 improved her productions of /k/ and /g/ at syllable level during the treatment period and achieved correct production at word level during follow-up. P3 made no improvements in his productions of velar targets. This study suggests that ultrasound visual feedback may be an option for remediating velar fronting in some preschoolers. Further study is required. PMID- 26810301 TI - Chlorogenic acid protects D-galactose-induced liver and kidney injury via antioxidation and anti-inflammation effects in mice. AB - CONTEXT: Oxidative stress and inflammation are implicated in the aging process and its related hepatic and renal function decline. Chlorogenic acid (CGA) is one of the most abundant polyphenol compounds in the human diet. Recently, CGA has shown in vivo and in vitro antioxidant properties. OBJECTIVE: The current study investigates the effects of protective effects of chlorogenic acid (CGA) on D galactose-induced liver and kidney injury. MATERIALS AND METHODS: Hepatic and renal injuries were induced in a mouse model by subcutaneously injection of D galactose (D-gal; 100 mg/kg) once a day for 8 consecutive weeks and orally administered simultaneously with CGA included in the food (200 mg/kg of diet). The liver and renal functions were examined. Histological analyses of liver and kidney were done by haematoxylin and eosin staining. The oxidative stress markers and pro-inflammatory cytokines in the liver and the kidney were measured. Results CGA significantly reduced the serum aminotransferase, serum creatinine (SCr) and blood urea nitrogen (BUN) levels in D-gal mice (p <0.05). CGA also restored superoxide dismutase, catalase, and malondialdehyde levels and decreased glutathione content in the liver and kidney in D-gal mice (p <0.05). Improvements in liver and kidney were also noted in histopathological studies. CGA reduced tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) protein levels in the liver and kidney in D-gal mice (p <0.05). DISCUSSION AND CONCLUSION: These findings suggest that CGA attenuates D-gal-induced chronic liver and kidney injury and that this protection may be due to its antioxidative and anti inflammatory activities. PMID- 26810304 TI - Assessment of the occupational and environmental risks of hexabromocyclododecane (HBCD) in China. AB - In 2013, hexabromocyclododecane (HBCD) was listed in the Stockholm Convention on Persistent Organic Pollutants obligated to be phased out worldwide. China is a major producer and user of HBCD. Based on Chinese HBCD production and processing conditions, we classified the existing 599 HBCD production and processing plants into six occupational exposure scenarios. We also used occupational environmental monitoring and occupational health risk assessment models to estimate exposure levels. Occupational internal exposure levels for HBCD in China were estimated to range from 0.61 to 840 MUg kg(-1) d(-1), which suggests that approximately 453 840 workers, or 72% of all workers in this industry, may have occupational exposure risk. As such, the occupational risks of HBCD should not be ignored. In our study area, HPLC-MS/MS revealed HBCD concentrations ranging from 0.11 to 560 ng g dry weight (dw)(-1), 20.4-24.2 ng g dw(-1), and 166-1964 ng g lipid weight (lw)(-1) in soil, sediment, and biological samples, respectively, consistent with previous monitoring results. These data suggest potential risk to marine environments due to sustained and large-scale HBCD production and processing. Thus, timely measures to control HBCD-related risk are necessary and may bring significant occupational health and environmental benefits in areas where HBCD is prevalent. PMID- 26810302 TI - Primary care physicians, acupuncture and chiropractic clinicians, and chronic pain patients: a qualitative analysis of communication and care coordination patterns. AB - BACKGROUND: A variety of people, with multiple perspectives, make up the system comprising chronic musculoskeletal pain (CMP) treatment. While there are frequently problems in communication and coordination of care within conventional health systems, more opportunities for communicative disruptions seem possible when providers use different explanatory models and are not within the same health management system. We sought to describe the communication system surrounding the management of chronic pain from the perspectives of allopathic providers, acupuncture and chiropractor (A/C) providers, and CMP patients. METHODS: We collected qualitative data from CMP patients (n = 90) and primary care physicians (PCPs) (n = 25) in a managed care system, and community acupuncture and chiropractic care providers (n = 14) who received high levels of referrals from the system, in the context of a longitudinal study of CMP patients' experience. RESULTS: Multiple points of divergence and communicative barriers were identified among the main stakeholders in the system. Those that were most frequently mentioned included issues surrounding the referral process (requesting, approving) and lack of consistent information flow back to providers that impairs overall management of patient care. We found that because of these problems, CMP patients were frequently tasked and sometimes overwhelmed with integrating and coordinating their own care, with little help from the system. CONCLUSIONS: Patients, PCPs, and A/C providers desire more communication; thus systems need to be created to facilitate more open communication which could positively benefit patient outcomes. PMID- 26810305 TI - Insights into the nanoscale lateral and vertical phase separation in organic bulk heterojunctions via scanning probe microscopy. AB - Solution processed polymer (donor) and fullerene (acceptor) bulk heterojunctions are widely used as the photo active layer in organic solar cells. Intimate mixing of these two materials is essential for efficient charge separation and transport. Identifying relative positions of acceptor and donor rich regions in the bulk heterojunction with nanometer scale precision is crucial in understanding intricate details of operation. In this work, a combination of Ar(+)2000 gas cluster ion beam and scanning probe microscopy is used to examine the lateral and vertical phase separation within regio-regular poly(3 hexylthiophene)(P3HT):phenyl-C60-butyric acid methyl ester (PCBM) bulk heterojunction. While the Ar(+)2000 gas cluster ion beam is used as a sputter tool to expose the underneath layers, scanning probe microscopy techniques are used to obtain two-dimensional (2D) electrical maps (with sub-2 nm lateral resolution). The electrical mapping is decoded to chemical composition, essentially producing lateral and vertical maps of phase separation. Thermal stress causes large PCBM-rich hillocks to form, and consequently affecting the balance of P3HT:PCBM heterojunctions, hence a negative impact on the efficiency of the solar cell. We further developed a method to analyze the efficiency of exciton dissociation based on the current maps and a loss of 20% in efficiency is observed for thermally degraded samples compared to fresh un-annealed samples. PMID- 26810307 TI - An engineered multicomponent bone marrow niche for the recapitulation of hematopoiesis at ectopic transplantation sites. AB - BACKGROUND: Bone marrow (BM) niches are often inaccessible for controlled experimentation due to their difficult accessibility, biological complexity, and three-dimensional (3D) geometry. METHODS: Here, we report the development and characterization of a BM model comprising of cellular and structural components with increased potential for hematopoietic recapitulation at ectopic transplantation sites. Cellular components included mesenchymal stromal cells (MSCs) and hematopoietic stem and progenitor cells (HSPCs). Structural components included 3D beta-tricalcium phosphate (beta-TCP) scaffolds complemented with Matrigel or collagen I/III gels for the recreation of the osteogenic/extracellular character of native BM. RESULTS: In vitro, beta TCP/Matrigel combinations robustly maintained proliferation, osteogenic differentiation, and matrix remodeling capacities of MSCs and maintenance of HSPCs function over time. In vivo, scaffolds promoted strong and robust recruitment of hematopoietic cells to sites of ectopic transplantation, vascularization, and soft tissue formation. CONCLUSIONS: Our tissue-engineered BM system is a powerful tool to explore the regulatory mechanisms of hematopoietic stem and progenitor cells for a better understanding of hematopoiesis in health and disease. PMID- 26810309 TI - Saline Groundwater from Coastal Aquifers As a Source for Desalination. AB - Reverse osmosis (RO) seawater desalination is currently a widespread means of closing the gap between supply and demand for potable water in arid regions. Currently, one of the main setbacks of RO operation is fouling, which hinders membrane performance and induces pressure loss, thereby reducing system efficiency. An alternative water source is saline groundwater with salinity close to seawater, pumped from beach wells in coastal aquifers which penetrate beneath the freshwater-seawater interface. In this research, we studied the potential use of saline groundwater of the coastal aquifer as feedwater for desalination in comparison to seawater using fieldwork and laboratory approaches. The chemistry, microbiology and physical properties of saline groundwater were characterized and compared with seawater. Additionally, reverse osmosis desalination experiments in a cross-flow system were performed, evaluating the permeate flux, salt rejection and fouling propensities of the different water types. Our results indicated that saline groundwater was significantly favored over seawater as a feed source in terms of chemical composition, microorganism content, silt density, and fouling potential, and exhibited better desalination performance with less flux decline. Saline groundwater may be a better water source for desalination by RO due to lower fouling potential, and reduced pretreatment costs. PMID- 26810308 TI - Are periodontal diseases really silent? A systematic review of their effect on quality of life. AB - AIM: Periodontal diseases (PDs) may play an important role in the effect oral health status has on a person's quality of life (QoL). The objective was to investigate the influence of PDs (gingivitis and periodontitis) on oral health related QoL (OHRQoL) by systematically reviewing the literature. MATERIALS AND METHODS: Studies using clinical periodontal examinations and validated survey instruments were included. Among 1134 citations initially identified through electronic and hand searching, 37 were eligible and data were extracted from full texts. A vote counting method was used for synthesis of the results. RESULTS: Included studies were published between 2001 and 2014 and revealed considerable heterogeneity in participant selection, clinical assessments, and OHRQoL measures. A significant association between PDs and OHRQoL was reported in 28 studies, of which eight reported increasing impact with greater disease severity or extent. CONCLUSIONS: Within the limits of the available literature, OHRQoL was affected by clinically assessed PDs. There was evidence for increased impairment with greater severity and extent of PDs, and the recognition of the association was increased when full mouth recording protocols were applied. PMID- 26810310 TI - Relationship between lateral differences in the cross-sectional area of the psoas muscle and curve running time. AB - BACKGROUND: The aim of this study was to investigate whether lateral differences in the cross-sectional areas of the hip and thigh muscles were related to curve sprinting time. METHODS: Thirteen college students (10 men and 3 women; mean +/- SD: age, 20.4 +/- 1.7 years; height, 167.6 +/- 8.9 cm; mass, 57.4 +/- 5.4 kg) participated in this study. The participants were instructed to sprint along a circular track (23 m radius) in the counterclockwise and clockwise directions. Magnetic resonance imaging was used to measure the cross-sectional area of the psoas major, quadriceps femoris, and hamstring muscles. The symmetry index was used to evaluate the lateral differences in the cross-sectional area. RESULTS: The lateral difference was observed in the cross-sectional area (CSA) of the thigh muscles, not in the psoas major muscle. The sprint time was not significantly different between the counterclockwise (22.15 +/- 2.27 s) and clockwise (22.13 +/- 2.32 s) directions. No significant correlations were found between the symmetry index of the thigh muscles and the cross-directional differences in sprint time. However, the symmetry index of the psoas major muscle correlated significantly with the cross-directional difference in sprint time (r = -0.614, P = 0.026). CONCLUSIONS: These findings suggest that the participants in whom the cross-sectional area of the psoas major muscle of the outer leg was larger than that of the inner leg were faster in curve sprinting. PMID- 26810311 TI - Statistical evaluation of methods for identification of differentially abundant genes in comparative metagenomics. AB - BACKGROUND: Metagenomics is the study of microbial communities by sequencing of genetic material directly from environmental or clinical samples. The genes present in the metagenomes are quantified by annotating and counting the generated DNA fragments. Identification of differentially abundant genes between metagenomes can provide important information about differences in community structure, diversity and biological function. Metagenomic data is however high dimensional, contain high levels of biological and technical noise and have typically few biological replicates. The statistical analysis is therefore challenging and many approaches have been suggested to date. RESULTS: In this article we perform a comprehensive evaluation of 14 methods for identification of differentially abundant genes between metagenomes. The methods are compared based on the power to detect differentially abundant genes and their ability to correctly estimate the type I error rate and the false discovery rate. We show that sample size, effect size, and gene abundance greatly affect the performance of all methods. Several of the methods also show non-optimal model assumptions and biased false discovery rate estimates, which can result in too large numbers of false positives. We also demonstrate that the performance of several of the methods differs substantially between metagenomic data sequenced by different technologies. CONCLUSIONS: Two methods, primarily designed for the analysis of RNA sequencing data (edgeR and DESeq2) together with a generalized linear model based on an overdispersed Poisson distribution were found to have best overall performance. The results presented in this study may serve as a guide for selecting suitable statistical methods for identification of differentially abundant genes in metagenomes. PMID- 26810312 TI - Identifying Key Intervention Opportunities During a Pregnancy Complicated by Diabetes: a Review of Acute Complications of Diabetes During Pregnancy. AB - Diabetes in pregnancy is associated with significant and sometimes devastating acute complications. It is important that all health care providers are aware of possible complications at each stage of pregnancy so that we can prevent these complications whenever possible and reduce morbidity when they do occur. Most complications associated with diabetes during pregnancy have reduced incidence when blood glucose and blood pressure are optimally controlled. Yet, it is always best to try to optimize diabetes and any comorbidities prior to conception. PMID- 26810313 TI - Intra-arterial revascularization therapy for basilar artery occlusion-a systematic review and analysis. AB - Acute basilar artery occlusion has been managed aggressively with various modalities due to its potentially debilitating outcome. While intra-arterial mechanical thrombectomy with stentriever has established clear evidence for anterior circulation stroke with large vessel occlusion as an adjunct to intravenous thrombolysis or the sole modality in intravenous thrombolysis ineligible patients, similar high-level evidence was not available for intra arterial mechanical thrombectomy of posterior circulation stroke with acute basilar artery occlusion. We hence perform a systematic review of current literature to compare intra-arterial pharmacological thrombolysis (IA-P) and intra-arterial mechanical thrombectomy (IA-MT) for acute basilar artery occlusion. Forty-one studies published between 1996 and 2015 were compared and studied by odds ratio analysis using Mantel-Haenszel risk ratio estimation, and time trend analysis using meta-regression. Patients in the IA-MT group were older, presented with more severe stroke, and more likely received treatment more than 12 h since onset of stroke. At 3 months, survival and clinical outcome were superior in the IA-MT group than the IA-P group, associated with higher recanalization rate. There were no difference between proportion of dependent survivors, and rate of symptomatic intracerebral hemorrhage across groups. Intra arterial thrombolysis with mechanical devices led to improved survival, better short-term clinical outcome and higher recanalization rate than intra-arterial pharmacological thrombolysis. PMID- 26810314 TI - Structural determinants of subtype selectivity and functional activity of angiotensin II receptors. AB - Agonists of the angiotensin II receptor type 2 (AT2), a G-protein coupled receptor, promote tissue protective effects in cardiovascular and renal diseases, while antagonists reduce neuropathic pain. We here report detailed molecular models that explain the AT2 receptor selectivity of our recent series of non peptide ligands. In addition, minor structural changes of these ligands that provoke different functional activity are rationalized at a molecular level, and related to the selectivity for the different receptor conformations. These findings should pave the way to structure based drug discovery of AT2 receptor ligands. PMID- 26810315 TI - Structure activity relationship, cytotoxicity and evaluation of antioxidant activity of curcumin derivatives. AB - Series of curcumin derivatives/analogues were designed and efficient method for synthesis thereof is described. All the synthesized compounds have been screened for their cytotoxicity and evaluated their antioxidant activity. Cytotoxicity effect has been evaluated against three cell lines Hep-G2, HCT-116 and QG-56 by MTT assay method. Structure activity relationship has revealed that particularly, compound 3c, (IC50 value 6.25 MUM) has shown better cytotoxicity effect against three cell lines. According to results of SAR study, it was found that 4H pyrimido[2,1-b]benzothiazole derivatives (2e and 2f), pyrazoles (3a, 3b, 3c and 3d) benzylidenes (4d) exhibited better antioxidant activity than curcumin. A correlation of structure and activities relationship of these compounds with respect to drug score profiles and other physico-chemical properties of drugs are described and verified experimentally. PMID- 26810316 TI - Discovery of 5-aryl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones as positive allosteric modulators of metabotropic glutamate subtype-2 (mGlu2) receptors with efficacy in a preclinical model of psychosis. AB - Optimization of a benzimidazolone template for potency and physical properties revealed 5-aryl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones as a key template on which to develop a new series of mGlu2 positive allosteric modulators (PAMs). Systematic investigation of aryl-SAR led to the identification of compound 27 as a potent and highly selective mGlu2 PAM with sufficient pharmacokinetics to advance to preclinical models of psychosis. Gratifyingly, compound 27 showed full efficacy in the PCP- and MK-801-induced hyperlocomotion assay in rats at CSF concentrations consistent with mGlu2 PAM potency. PMID- 26810317 TI - Emerging Technologies to Conserve Biodiversity: Further Opportunities via Genomics. Response to Pimm et al. PMID- 26810318 TI - Validation of the modified Japanese Triage and Acuity Scale-based triage system emphasizing the physiologic variables or mechanism of injuries. AB - BACKGROUND: The Canadian Triage and Acuity Scale is a valid triage system. The system was translated and implemented in the Japanese emergency departments (EDs) from 2012. This system was named the Japanese Triage and Acuity Scale; however, the validation studies of the Japanese Triage and Acuity Scale have been limited. In addition, for a patient with multiple complaints, it could become challenging, due to its requirement of a single complaint. Therefore, we hypothesized that a modified version of the Japanese Triage and Acuity Scale using first-order modifiers without chief complaint detection is accurate. METHODS: A retrospective cohort study evaluated a correlation between the modified triage scale level and outcomes of all adult emergency department patients at a Japanese hospital. Construct validity of the modified triage scale level was assessed based on comparisons of total admission rate (including hospitalizations, emergency department deaths) and length of stay between triage levels. RESULTS: The distributions of five levels of the triage scale (level 1 is the most urgent) among the 17,121 cases are as follows: 1:451, 2:1148, 3:7703, 4:7652, and 5:167. Total admission rates by each level were 1:89.8, 2:68.2, 3:26.4, 4:6.6, and 5:0.6 %, which progressively increased from level 5 to 1 and were significant (p < 0.01). Compared with patients in level 3, the odds of total admission rates were 14.4, 5.1, 0.27, and 0.030 for the patients in levels 1, 2, 4, and 5. The length of stay was longer in the patients with the more urgent levels except for those with level 1. CONCLUSIONS: The modified version of the Japanese Triage and Acuity Scale is a valid predictor of total admission and length of stay and may enable the nurses to triage patients without detecting the chief complaints. PMID- 26810319 TI - Fetal and neonatal alloimmune thrombocytopenia. AB - Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is an alloimmune disorder resulting from platelet opsonization by maternal antibodies that destroy fetal platelets. The major risk of FNAIT is severe bleeding, particularly intracranial hemorrhage. Miscarriage has also been reported but the incidence requires further study. Analogous to adult autoimmune thrombocytopenia (ITP), the major target antigen in FNAIT is the platelet membrane glycoprotein (GP)IIbIIIa. FNAIT caused by antibodies against platelet GPIbalpha or other antigens has also been reported, but the reported incidence of the anti-GPIbalpha-mediated FNAIT is far lower than in ITP. To date, the maternal immune response to fetal platelet antigens is still not well understood and it is unclear why bleeding is more severe in FNAIT than in ITP. In this review, we introduce the pathogenesis of FNAIT, particularly those new discoveries from animal models, and discuss possible improvements for the diagnosis, therapy, and prevention of this devastating disease. PMID- 26810321 TI - Incidence of isolated dipstick hematuria and its association with the glomerular filtration rate: a cross-sectional study from the Korean National Health and Nutrition Examination Survey V (2010-2012). AB - PURPOSE: To investigate the incidence of isolated hematuria and its relationship to the glomerular filtration rate (GFR). METHODS: Data from the Korean National Health and Nutrition Examination Survey V were used. A stratified, three-stage, clustered probability design was used to collect representative data on the Korean population. Ultimately, 18,587 participants were included. The incidence of isolated dipstick hematuria and its relationship with the GFR (estimated by the Chronic Kidney Disease Epidemiology Collaboration equation) were evaluated. RESULTS: The analysis showed that 31.8% of the population had isolated hematuria, the incidence of which significantly increased with age (P trend < 0.001). As the severity of hematuria increased, the ratio of GFR < 60 ml/min/1.73 m(2) and 60 ml/min/1.73 m(2) <= GFR < 90 ml/min/1.73 m(2) was significantly increased (P trend < 0.001). After adjusting for the confounders, the mean GFR of the grade 3+ (grades 3, 4, 5) hematuria group was significantly reduced compared to that of the negative, grade 1, and grade 2 hematuria groups (with an adjusted mean +/- standard error of 94.0 +/- 0.8 vs. 97.2 +/- 0.3 ml/min/1.73 m(2), P < 0.001). Additionally, the odds ratio of the grade 3+ hematuria group for a GFR < 60 ml/min/1.73 m(2) was significantly increased compared to that of the negative, grade 1, and grade 2 hematuria groups after adjusting for the confounders (adjusted odds ratio 1.468, 95% confidence interval 1.049-2.054, P = 0.025). CONCLUSION: An effective health policy for hematuria screening is needed for older age groups. A strategy of careful checkups and counseling regarding renal function is necessary for patients with isolated hematuria. PMID- 26810320 TI - Psychosocial factors associated with early initiation and frequency of antenatal care (ANC) visits in a rural and urban setting in South Africa: a cross-sectional survey. AB - BACKGROUND: Late booking and infrequent antenatal care (ANC) are common but avoidable patient-related risk factors for maternal deaths in South Africa. The aim of the study was to examine the association of psychosocial factors with early initiation of ANC and adequate frequency of attendance of ANC clinics among women in an urban and rural location in South Africa. METHODS: Data from a 2006 cross-sectional household survey of 363 women from the rural Western Cape and 466 women from urban Gauteng provinces of South Africa for risk of alcohol-exposed pregnancy were analysed. We examined associations between psychosocial variables (self-esteem, cultural influences, religiosity, social capital, social support, pregnancy desire (wanted versus unwanted pregnancy), partner characteristics and mental health) and both early ANC first visit (before 16 weeks) and adequate frequency of ANC visits (4 or more visits) for respondents' last pregnancy. RESULTS: Overall prevalence among urban women of early ANC initiation was 46% and 84% for adequate ANC frequency. Overall prevalence among rural women of early ANC initiation was 45% and 78% for adequate ANC frequency. After adjusting for clustering, psychosocial factors associated with early ANC initiation in the urban site were being employed (OR 1.6; 95% CI 1.0-2.5) and wanted pregnancy (OR 1.8; 95% CI 1.1-3.0). For the rural site, early ANC initiation was significantly associated with being married (OR 1.93; 95% CI 1.0-3.6) but inversely associated with high religiosity (OR 0.5; 95% CI 0.3-0.8). Adequate frequency of ANC attendance in the rural site was associated with wanted pregnancy (OR 4.2; 95% CI 1.9-9.3) and the father of the child being present in the respondent's life (OR 3.0; 95% CI 1.0-9.0) but inversely associated with having a previous miscarriage (OR 0.4; 95% CI 0.2-0.8). There were no significant associations between adequate ANC attendance and the psychosocial factors in the urban site. CONCLUSION: The majority of women from both sites attended ANC frequently but less than 50% initiated ANC before the recommended 16 weeks gestational age. Interventions to reduce prevalence of late ANC booking and inadequate ANC attendance should engage religious leaders, address unintended pregnancy through family planning education and involve male partners in women's reproductive health. PMID- 26810322 TI - The impact of preoperative anemia on oncologic outcome in patients undergoing radical cystectomy for urothelial carcinoma of the bladder. AB - PURPOSE: To investigate the impact of preoperative anemia (PA) on oncologic outcomes among patients who underwent radical cystectomy (RC) for bladder cancer. METHODS: We reviewed the records of 200 patients undergoing RC between October 2003 and December 2014. Patients were categorized according to PA status. We performed multivariable Cox regression analyses to assess the impact of PA on oncological outcomes. RESULTS: Among 200 patients, 81 patients (40.5%) had PA according to definition of the WHO classification. Fifty-two (26%) of 200, 12 (6%) of 200 and 61 (30.5%) of 200 patients experienced the disease recurrence (DR), cancer-specific mortality (CSM) and all-cause mortality (ACM), respectively. In Kaplan-Meier analysis, the non-PA group showed a significantly higher 5-year DR-free survival than PA group (log-rank test: p = 0.018). The non PA group showed a similar pattern of CSM and ACM (p = 0.004 and p = 0.037, respectively). In multivariable Cox proportional hazards analysis, PA was significantly associated with DR (HR 1.86, 95% CI, p = 0.04) and ACM (HR 2.13, 95% CI, p = 0.006) after adjusting other factors. CONCLUSIONS: The preoperative anemic bladder cancer patients who underwent RC had worse oncological outcomes than non-anemic bladder cancer patients. PMID- 26810323 TI - Developing a model for forecasting Gleason score >=7 in potential prostate cancer patients to reduce unnecessary prostate biopsies. AB - PURPOSE: The diagnosis of Gleason score (GS) >=7 with distinction from GS < 7 remains a difficult problem instructing clinical decisions. Moreover, the present wide application of prostate biopsy to increase prostate cancer detection rate might cause unnecessary and excessive examination or treatment. Therefore, a risk assessment model for forecasting GS >= 7 in potential prostate cancer patients was established to reduce unnecessary prostate biopsies. METHODS: Patients (n = 981; September 2009 to January 2013) who underwent trans-rectal ultrasound (TRUS) guided core prostate biopsy were retrospectively evaluated in the first stage of the study. Age, prostate-specific antigen (PSA), free PSA (fPSA), the free/total PSA ratio (f/t), prostate volume (PV), PSA density (PSAD), digital rectal examination (DRE) findings (texture, nodules) and B-ultrasound detection results (normal or abnormal, presence of hypoechoic mass or microcalcification) were considered as potential predictive factors. After multiple logistic regression analysis, independent variables used to build a nomogram were selected using a backward elimination selection procedure. Then, a model to forecast GS >= 7 was designed for potential prostate cancer patients. In the second stage of the study, 410 cases (January 2013 to March 2015) were subsequently evaluated using our model for prostate biopsies, and the outcomes of biopsies were compared between the two stages. RESULTS: PSA, DRE texture, DRE nodules and B-ultrasound results were finally brought into our nomogram; a obviously greater area under the receiver operating characteristic (ROC) curve was obtained for the model than utilizing PSA, fPSA or PSAD alone (0.831 vs. 0.803, 0.770, 0.780 separately). We thereafter sought the best cutoff value in the ROC curve at 0.87, which provided sensitivity as high as 90%. Meanwhile, the specificity was 45.8%, which was much higher than the specificity of PSA, fPSA and PSAD at the same sensitivity level (37.7, 24.6 and 35.2%, respectively). In the first stage, the detection rate of GS >= 7 in the high-risk group was significantly higher than in the low-risk group (80.3 vs. 35.0%, p < 0.001). Furthermore, in the second stage, with the application of the new model associated with our former models, the rate of GS >= 7 was improved from 71.0 (697/981) to 79.2% (267/337) (p = 0.003). CONCLUSIONS: The model for forecasting GS >= 7 is effective, which could reduce unnecessary prostate biopsies without delaying patients' diagnoses and treatments. PMID- 26810324 TI - Quality of life in patients with lower urinary tract symptoms associated with BPH: change over time in real-life practice according to treatment--the QUALIPROST study. AB - PURPOSE: To evaluate change in quality of life (QoL) and symptoms in patients with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) in conditions of current clinical practice. METHODS: Prospective, longitudinal, multicenter open-label study was carried out in urology outpatient clinics. Patients were >=40 years of age with an International Prostate Symptom Score (IPSS) score >= 8. QoL and symptoms were measured at baseline and 6 months using the Benign Prostatic Hyperplasia Impact Index (BII) and the IPSS. RESULTS: 1713 patients were included for analysis. Mean (SD) IPSS and BII scores at baseline were 16.8 (5.4) and 6.8 (2.6), respectively. 8.9 % (n = 153) of study participants did not receive treatment (watchful waiting, WW), 70.3 % (n = 1204) were prescribed monotherapy (alpha-adrenergic blockers [AB]; phytotherapy [PT, of which 95.2 % was the hexanic extract of Serenoa repens, HESr]; or 5-alpha reductase inhibitors [5ARI]), and 20.8 % (n = 356) received combined treatment (AB + 5ARI; AB + HESr; others). At 6 months, improvements in QoL were similar across the different medical treatment (MT) groups, both for monotherapy (AB: mean improvement [SD] of 2.4 points [2.4]; PT: 1.9 [2.4]; 5ARI: 2.5 [2.3]) and combined therapy (AB + 5ARI: 3.1 [2.9]; AB + PT: 3.1 [2.5]). There were no clinically significant differences between MT groups and all showed significant improvement over WW (p < 0.05). HESr showed similar efficacy to AB and 5ARI both as monotherapy and in combination with AB. Results on the IPSS were similar. CONCLUSIONS: Improvements in QoL and symptoms were equivalent across the medical treatments most widely used in real-life practice to manage patients with moderate or severe LUTS. HESr showed an equivalent efficacy to AB and 5ARI with fewer side effects. PMID- 26810326 TI - [Angiographic procedures for determination of cessation of cerebral circulation]. AB - In several European countries catheter angiography is permitted as a confirmatory procedure for the determination of irreversible loss of brain function (brain death). In Germany catheter angiography requires the possibility of a therapeutic implication as a prerequisite. In the updated German guidelines computed tomography angiography (CTA) has been accredited as a new confirmatory procedure if a standardized protocol and predefined assessment parameters are adhered to. The CTA can be performed within a few minutes, even in situations with unstable intensive care patients. Magnetic resonance (MR) angiography has not yet been adequately validated and is not permitted in Germany as a confirmatory procedure for the determination of irreversible loss of brain function. PMID- 26810328 TI - Adolescents' health-related quality of life (HRQoL) changes over time: a three year longitudinal study. AB - BACKGROUND: Adolescence is a significant developmental stage marked by physical, psychological and social changes. While adolescents are generally perceived to be healthy, this stage of development is also associated with an emergence of risk factors that may have long-term consequences for their wellbeing. The aim of this study was to assess health related quality of life (HRQoL), and possible gender and age differences, in a sample of secondary school-aged adolescents over a three-year time period. METHODS: Australian adolescents (n = 403, aged 12-15 at baseline) across six New South Wales high schools completed the KIDSCREEN-27 Questionnaire at three time points. The KIDSCREEN-27 measures five HRQoL domains (physical wellbeing, psychological wellbeing, autonomy and parents relations, social support and peers, and school environment). Mixed-between-within-subjects ANOVA analyses were employed to examine HRQoL over time and across age and gender. RESULTS: HRQoL rates were comparable to the European-based KIDSCREEN norms with the exception of psychological wellbeing, which was considerably lower in this study's sample. Over time, for the total sample, there were significant changes on only one of the five dimensions (social support and peers). However, gender differences were found to be significant across three dimensions (physical wellbeing, psychological wellbeing, and autonomy and parents relations), with females reporting lower scores than males (i.e. lower HRQoL). Females' scores also declined over the three time points across two of the five HRQoL dimensions (social support and peers, and school environment), indicating reductions in HRQoL over time. Age differences were found across all but one dimension (autonomy and parents relations). CONCLUSIONS: Although statistically significant, the changes in HRQoL may not be clinically significant, as the effect sizes were small and therefore those changes would not be readily noticeable. Those changes, however, suggest that, while HRQoL is predominantly stable over time, fluctuations and declines, such as those found for females, may be early indicators of physical and psychological vulnerabilities. If such vulnerabilities are detected timely; they may be addressed with preventative measures or appropriate interventions. PMID- 26810329 TI - ERRATUM TO: Quantitation of Mitochondrial DNA Deletions Via Restriction Digestion/Long-Range Single-Molecule PCR. PMID- 26810331 TI - Lipodystrophia Centrifugalis Abdominalis Infantilis: A Case in a Vietnamese Patient. AB - BACKGROUND: Lipodystrophia centrifugalis abdominalis infantilis (LCAI) is an uncommon dermatological condition characterized by a centrifugally expanding area of lipoatrophy involving the lower abdominal area and is frequently associated with inguinal lymphadenopathy. The average age of onset is 4 years and female individuals from Japan, China, and Korea are affected more often. OBJECTIVES: To report the first case of LCAI in a Vietnamese patient. METHODS: A complete clinical assessment was done and a biopsy from the affected area was performed. RESULTS: There was an atrophic, slightly hyperpigmented patch at the lower abdomen with prominent underlying vasculature. Inguinal lymphadenopathy was noted on the ipsilateral side. A biopsy showed a lobular panniculitis with fat necrosis and lymphohistiocytic infiltrate with scattered plasma cells and multinucleated giant cells. CONCLUSION: To our knowledge, this is the first reported case of LCAI in a Vietnamese patient. PMID- 26810333 TI - Successful conservative management of symptomatic bilateral dorsal patellar defects presenting with cartilage involvement and bone marrow edema: MRI findings. AB - The dorsal patellar defect is a relatively rare entity that involves the superolateral quadrant of the patella. It is usually considered to represent a delayed ossification process, although its exact origin remains unclear. Because of its usually innocuous nature and clinical course, invasive interventions are generally deemed unnecessary, although curretage has been successfully performed on symptomatic cases. This case report presents a rather unusual case of symptomatic bilateral dorsal patellar defects with cartilage involvement and widespread surrounding bone marrow edema as demonstrated by magnetic resonance imaging (MRI). Both cartilage involvement and bone marrow edema should be considered part of the spectrum of associated MRI findings that can be encountered in this entity. Furthermore, the presented case shows that symptomatic dorsal patellar defects can be treated conservatively with success and that (decrease of) pain symptoms are likely related to (decrease of) bone marrow edema. PMID- 26810334 TI - [Multiple tumors breast cancer: Did you say "DANGER"? A pedagogical tool for residents]. PMID- 26810335 TI - Isolation of atypical enteropathogenic Escherichia coli from chicken and chicken derived products. AB - Atypical enteropathogenic Escherichia coli (EPEC) strains from chicken and chicken-derived products were isolated and characterised. The strains presented a wide variety of serotypes, some have been reported in other animal species (O2:H40, O5:H40) and in children with diarrhoea (O8:H-). Most of the strains carried intimin beta. The results indicate that chicken and chicken products are important sources of atypical EPEC strains that could be associated with human disease, and highlight the need to improve hygiene practices in chicken slaughtering and meat handling. PMID- 26810336 TI - Formation of Negative Ions upon Dissociative Electron Attachment to the Astrochemically Relevant Molecule Aminoacetonitrile. AB - Aminoacetonitrile (NH2CH2CN, AAN) is a molecule relevant for interstellar chemistry and the chemical evolution of life. It is a very important molecule in the Strecker diagram explaining the formation of amino acids. In the present investigation, dissociative electron attachment to NH2CN was studied in a crossed electron-molecular beams experiment in the electron energy range from about 0 to 17 eV. In this electron energy range, the following six anionic species were detected: C2H3N2(-), C2H2N2(-), C2H2N(-), C2HN(-), CN(-), and NH2(-). Possible reaction channels for all the measured negative ions are discussed, and the experimental results are compared with calculated thermochemical thresholds of the observed anions. Similar to other nitrile and aminonitrile compounds, the main anions detected were the negatively charged nitrile group, the dehydrogenated parent molecule, and the amino group. No parent anion was observed. Low anion yields were observed indicating that AAN is less prone to electron capture. Therefore, AAN can be considered to exhibit a relatively long lifetime under typical conditions in outer space. PMID- 26810337 TI - Assessment of the quality of clinical documentation in India's JSY cash transfer program for facility births in Madhya Pradesh. AB - OBJECTIVE: To gain insight into the quality of care in facilities implementing the Janani Suraksha Yojana (JSY) cash transfer program in Madhya Pradesh, India, by reviewing the level of documentation in the clinical records of women who delivered. METHODS: The present retrospective, descriptive study reviewed case records of women who delivered at 73 primary, secondary, and tertiary level facilities in three districts of Madhya Pradesh between 2012 and 2013. Twenty elements of care were assessed encompassing clinical history and admission details, care during delivery and postnatal period, and discharge details. RESULTS: A total of 1239 records were reviewed. The extent of documentation varied among the elements assessed-e.g. 24 (1.9%) records documented advice at discharge, 171 (13.8%) documented postnatal blood pressure, 437 (35.3%) documented fetal heart rate, and 1220 (98.5%) documented admission date. The extent of documentation was better at higher level facilities. CONCLUSION: The quality of clinical documentation in the JSY program was found to be unacceptably poor in Madhya Pradesh. Improving staff skills and practices in clinical documentation and record keeping will be required to enable clinical processes to be assessed and quality of care to be improved. PMID- 26810338 TI - Randomized controlled study of pre-conception thromboprophylaxis among patients with recurrent spontaneous abortion related to antiphospholipid syndrome. AB - OBJECTIVES: To investigate the effects of pre-conception thromboprophylaxis among patients with recurrent spontaneous abortion and antiphospholipid syndrome. METHODS: A randomized placebo-controlled trial enrolled patients with a history of recurrent spontaneous abortions and antiphospholipid syndrome who attended an Egyptian center between January 2011 and June 2013. Using a computer-generated sequence, patients were randomly allocated to receive 41 mg enoxaparin subcutaneously plus 81 mg aspirin daily pre-conception, or to receive placebo pre conception. All patients received enoxaparin and aspirin following identification of fetal heart pulsation. The primary outcomes were live-birth rate and clinical pregnancy rate at 0-6 months, and at 6-12 months. Intention-to-treat analyses were performed. Clinicians, investigators, and data analysts were masked to the treatment assignments. RESULTS: The study enrolled 180 patients(90 in each group). No significant difference was observed between the intervention and control groups in the live-birth rate (67[74%] vs 59[66%]; P=0.25). At 0-6 months, the clinical-pregnancy rate was higher in the intervention group (50[56%]vs 30[33%], P=0.02). No significant difference between the intervention and control groups was observed in the clinical-pregnancy rate at 6-12 months (32[36%] vs 35[39%], P=0.52). CONCLUSION: Among patients with recurrent spontaneous abortion and antiphospholipid syndrome, pre-conception enoxaparin increased the clinical-pregnancy rate at 0-6 months, but did not affect the clinical-pregnancy rate at 6-12 months or the live-birth rate. ClinicalTrials.gov: NCT01661439. PMID- 26810339 TI - The unfinished agenda of women's reproductive health. PMID- 26810340 TI - Early prediction of hypertension during pregnancy in a low-resource setting. AB - OBJECTIVE: To evaluate the role of maternal factors, biomarkers, and uterine artery Doppler in the prediction of hypertension during pregnancy. METHODS: A prospective cohort study was performed between December 2012 and November 2014. All singleton pregnancies between 11 weeks and 13 weeks, 6 days of pregnancy were included. Patients had their body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters), mean arterial pressure, uterine-artery Doppler pulsatility index, and pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin levels recorded. Any patients diagnosed with hypertension during follow-up were assigned to the case cohort; all other patients were assigned to the control group. RESULTS: Hypertension during pregnancy was observed in 198 (9.7%) of 2042 patients that attended follow-up. The mean BMI, mean arterial pressure, uterine-artery Doppler pulsatility index, and the PAPP-A level at study enrollment were all significantly correlated with the later development of hypertension (P<0.001 for all variables). The combined sensitivity, specificity, positive predictive value, and negative predictive value of using the investigated parameters to predict hypertension was 76%, 80%, 31%, and 93%, respectively. CONCLUSION: Patient BMI, mean arterial pressure, PAPP-A, and pulsatility index were found to be effective predictors of hypertension during pregnancy. Combining these predictors may be beneficial in selecting individuals for close monitoring and early intervention during pregnancy. PMID- 26810342 TI - A Compression Kit of a Stocking and Three Superimposed Leggings Is Easy to Don and Dose Adjustable. AB - BACKGROUND: Forty percent of patients with chronic venous insufficiency (CVI) do not wear their indicated and prescribed compression stockings. Difficulties in donning and a feeling of constraint are the most common reasons for non adherence. OBJECTIVE: The aim was to develop a compression stocking system that is easy to don and dose adjustable. METHODS: A modular compression stocking kit composed of an understocking and three superimposable leggings (SLLLs) was developed. Substocking pressures (P) at the thinnest part above the ankle (cB level) were 17 mm (understocking) + 15 + 10 + 10 mmHg (3 superimposed leggings; Hatra method). Twenty healthy subjects and 20 patients over 65 years with CVI donned the SLLL compression kit. P was measured in vivo (Picopress method) at the transition of the Achilles tendon to the calf muscle (level cB1) during rest and ankle movements (DSI; dynamic stiffness index) and compared with a strong compression stocking of 40 mmHg (S40). RESULTS: Twenty (20/20) patients aged over 65 with CVI (C4-6) successfully donned the SLLL compression kit without aid, compared with 12 (12/20) who were able to don the S40 without aid (p = .02). In vivo resting P at level cB1 was 34.3 mmHg (SLLL) compared with 37.3 mmHg (S40) (p = .1). The DSI was 16.1 (SLLL) compared with 17.9 (p = .79; S40; CVI group). CONCLUSION: The physical properties of the SLLL compression stocking kit correspond to the characteristics of a strong stocking at rest and exercise (DSI). The donning success rate is excellent (100%). A further potential advantage is that the SLLL leg compression kit is dose adjustable, according to indication or patient tolerance. Wearing comfort over periods of several days and clinical effectiveness need to be investigated in future trials. PMID- 26810343 TI - Anemia Increases Mortality After Open or Endovascular Treatment in Patients with Critical Limb Ischemia: A Retrospective Analysis. AB - OBJECTIVES: Pre-operative anemia has been associated with increased post operative morbidity and mortality in elective cardiac surgery, but its association with post-operative mortality after open or endovascular surgery for critical limb ischemia (CLI) is not well established. The aim of this study was to evaluate the relationship between pre-operative anemia and mortality in surgery for CLI. MATERIALS AND METHODS: A retrospective study of 403 consecutive patients (mean age = 73; 73% male) undergoing open (n = 191, 47%) or endovascular (n = 212, 53%) surgery for CLI between 2005 and 2013 was performed. Neither redo revascularization procedures (ipsilateral or contralateral) nor acute limb ischemia patients were included as new cases. RESULTS: The best cut off (receiver operating characteristic curve) that related pre-operative hemoglobin to mortality was 10 g/dL. The immediate (in hospital or < 30 days) mortality rate was 8% (32 patients), with no significant differences between open and endovascular surgery. Patients with a pre-operative hemoglobin <10 g/dl had a higher immediate mortality rate (17.7% vs. 5.1%), with a risk (OR), adjusted by age and prior myocardial infarction, of 3.9, 95% CI 1.8-8.4 (p = 0.001). The mean follow up of the cohort was 30 months (97% complete). Similarly, a pre-operative hemoglobin <10 g/dL was significantly associated with a lower 1 year (55 vs. 83%) and 5 year survival rate (21 vs. 53%) with an associated risk (HR) of 2.5, 95% CI 1.8-3.4 (p < 0.001) adjusted by age, previous myocardial infarction, chronic renal failure, stroke, diabetes mellitus, and ischemic ulcers. CONCLUSIONS: Pre operative anemia is a risk factor for immediate and late mortality among patients with CLI, regardless of other risk factors and the type of revascularization technique. Prospective studies are needed to evaluate the potential effect of its treatment on survival outcomes. PMID- 26810344 TI - Commentary on 'Predictors of Stroke, Myocardial Infarction, or Death within 30 Days of Carotid Artery Stenting: Results from the International Carotid Stenting Study.' An Old Story (Not for Old Patients). PMID- 26810345 TI - 68Ga-PSMA Positron Emission Tomography/Computed Tomography Provides Accurate Staging of Lymph Node Regions Prior to Lymph Node Dissection in Patients with Prostate Cancer. AB - We evaluated the accuracy of 68Ga-prostate-specific membrane antigen-HBED-CC (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT) for nodal staging prior to lymph node dissection (LND) in patients with prostate cancer (PCa). Thirty-four patients with histologically proven PCa underwent 68Ga-PSMA HBED-CC PET/CT prior to radical prostatectomy with primary LND (pLND; n=20) and PET/CT prior to secondary LND (sLND; n=14). Accuracy of PET and CT were analysed separately for staging of the following 71 lymph node (LN) regions: pelvic left (n=30), pelvic right (n=31), presacral (n=3), and para-aortic (n=7). Postoperative histopathology was taken as a reference standard. Thirty-seven of 71 (52%) regions showed LN metastases on histopathology. Sensitivity, specificity, positive predictive value, and negative predictive value for detection of LN metastases were 84%, 82%, 84%, and 82% for PET criteria and 65%, 76%, 75%, and 67% for CT criteria. PET was more accurate for nodal staging compared with CT both at pLND (88% vs 75%) and sLND (77% vs 65%). Overall, 68Ga PSMA PET/CT provides accurate nodal staging prior to pLND and sLND for PCa. PATIENT SUMMARY: 68Ga-PSMA positron emission tomography/computed tomography is accurate in detecting tumour spread to lymph nodes before patients undergo surgery for prostate cancer. PMID- 26810347 TI - Is it Time to Start Quantifying the Amount of High-grade Cancer on Pathology? PMID- 26810349 TI - Lymphopenia can be a useful biomarker of adverse events related to vemurafenib. PMID- 26810346 TI - Multiparametric Magnetic Resonance Imaging (MRI) and MRI-Transrectal Ultrasound Fusion Biopsy for Index Tumor Detection: Correlation with Radical Prostatectomy Specimen. AB - BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) and MRI fusion targeted biopsy (FTB) detect significant prostate cancer (sPCa) more accurately than conventional biopsies alone. OBJECTIVE: To evaluate the detection accuracy of mpMRI and FTB on radical prostatectomy (RP) specimen. DESIGN, SETTING AND PARTICIPANTS: From a cohort of 755 men who underwent transperineal MRI and transrectal ultrasound fusion biopsy under general anesthesia between 2012 and 2014, we retrospectively analyzed 120 consecutive patients who had subsequent RP. All received saturation biopsy (SB) in addition to FTB of lesions with Prostate Imaging Reporting and Data System (PI-RADS) score >=2. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The index lesion was defined as the lesion with extraprostatic extension, the highest Gleason score (GS), or the largest tumor volume (TV) if GS were the same, in order of priority. GS 3+3 and TV >=1.3ml or GS >=3+4 and TV >=0.55ml were considered sPCa. We assessed the detection accuracy by mpMRI and different biopsy approaches and analyzed lesion agreement between mpMRI and RP specimen. RESULTS AND LIMITATIONS: Overall, 120 index and 71 nonindex lesions were detected. Overall, 107 (89%) index and 51 (72%) nonindex lesions harbored sPCa. MpMRI detected 110 of 120 (92%) index lesions, FTB (two cores per lesion) alone diagnosed 96 of 120 (80%) index lesions, and SB alone diagnosed 110 of 120 (92%) index lesions. Combined SB and FTB detected 115 of 120 (96%) index foci. FTB performed significantly less accurately compared with mpMRI (p=0.02) and the combination for index lesion detection (p=0.002). Combined FTB and SB detected 97% of all sPCa lesions and was superior to mpMRI (85%), FTB (79%), and SB (88%) alone (p<0.001 each). Spearman's rank correlation coefficient for index lesion agreement between mpMRI and RP was 0.87 (p<0.001). Limitations included the retrospective design, multiple operators, and nonblinding of radiologists. CONCLUSIONS: MpMRI identified 92% of index lesions compared with RP histopathology. The combination of FTB and SB was superior to both approaches alone, reliably detecting 97% of sPCa lesions. PATIENT SUMMARY: Multiparametric magnetic resonance imaging detects the index lesion accurately in 9 of 10 patients; however, the combined biopsy approach, while missing less significant cancer, comes at the cost of detecting more insignificant cancer. PMID- 26810351 TI - Correlated changes in body shape after five generations of selection to improve growth rate in a breeding program for Nile tilapia Oreochromis niloticus in Brazil. AB - Body shape is a commercial trait of great interest as it impacts profit and productivity of aquaculture enterprises. In the present study, we examined correlated changes in two measures of body shape (depth to length ratio, DL-R and ellipticity of mid sagittal plane, EL-H) from a selection program for high daily weight gain in a Nile tilapia population reared in freshwater cages in Brazil. Genetic parameters for body shape and its genetic association with growth traits (body weight and daily gain) were also estimated from 8,725 individuals with growth performance recorded over five generations from 2008 to 2013. Mixed model analysis showed that the selection program resulted in substantial improvement in growth performance (about 4 % genetic gain per generation or per year) and also brought about trivial changes in body shape. The heritabilities ranged from 0.470 to 0.564 for growth traits and 0.180 to 0.289 for body shape. The common family effects were low for all traits studied, accounting for only 3-11 % of total phenotypic variance. The genetic correlations between body shape and growth traits were weak, i.e., -0.385 between EL-H and growth traits and 0.28 between DL R and body weight or daily gain. Strong and negative genetic association was found between the two body shape traits (rg = --0.955). Harvest body weight and daily gain are essentially the same traits, as indicated by the close to one genetic correlations between the two characters. Our results demonstrated that the selection process to increase growth rate had small, but slowly constant effect in body shape traits; and in the long term, the fish would have become rotund. PMID- 26810352 TI - [Not Available]. PMID- 26810354 TI - Early cranioplasty: Need more evidence to be recommended as guidance. PMID- 26810355 TI - The Relationship Between Shift Work and Metabolic Risk Factors: A Systematic Review of Longitudinal Studies. AB - CONTEXT: Although the metabolic health effects of shift work have been extensively studied, a systematic synthesis of the available research is lacking. This review aimed to systematically summarize the available evidence of longitudinal studies linking shift work with metabolic risk factors. EVIDENCE ACQUISITION: A systematic literature search was performed in 2015. Studies were included if (1) they had a longitudinal design; (2) shift work was studied as the exposure; and (3) the outcome involved a metabolic risk factor, including anthropometric, blood glucose, blood lipid, or blood pressure measures. EVIDENCE SYNTHESIS: Eligible studies were assessed for their methodologic quality in 2015. A best-evidence synthesis was used to draw conclusions per outcome. Thirty-nine articles describing 22 studies were included. Strong evidence was found for a relation between shift work and increased body weight/BMI, risk for overweight, and impaired glucose tolerance. For the remaining outcomes, there was insufficient evidence. CONCLUSIONS: Shift work seems to be associated with body weight gain, risk for overweight, and impaired glucose tolerance. Overall, lack of high-methodologic quality studies and inconsistency in findings led to insufficient evidence in assessing the relation between shift work and other metabolic risk factors. To strengthen the evidence, more high-quality longitudinal studies that provide more information on the shift work schedule (e.g., frequency of night shifts, duration in years) are needed. Further, research to the (mediating) role of lifestyle behaviors in the health effects of shift work is recommended, as this may offer potential for preventive strategies. PMID- 26810356 TI - Self-Perceived Emotional Distress and Diabetes Risk Among Young Men. AB - INTRODUCTION: There are mixed data regarding the effect of emotional distress on diabetes risk, especially among young adults. This study assessed the effect of self-perceived emotional distress on diabetes incidence among young men. METHODS: Incident diabetes during a mean follow-up of 6.3 (4.3) years was assessed among 32,586 men (mean age, 31.0 [5.6] years) of the Metabolic, Lifestyle, and Nutrition Assessment in Young Adults cohort with no history of diabetes between 1995 and 2011. Emotional distress was assessed by asking participants as part of a computerized questionnaire: Are you preoccupied by worries or concerns that affect your overall wellbeing? Time-dependent Cox models were applied. Data analysis took place between 2014 and 2015. RESULTS: There were 723 cases of diabetes during 206,382 person-years. The presence of distress was associated with a 53% higher incidence of diabetes (95% CI=1.08, 2.18, p=0.017) after adjustment for age, BMI, fasting plasma glucose, family history of diabetes, triglyceride and high-density lipoprotein cholesterol levels, education, cognitive performance, white blood cell count, physical activity, and sleep quality. These results persisted when distress, BMI, physical activity, and smoking status were treated as time-dependent variables (hazard ratio=1.66, 95% CI=1.21, 2.17, p=0.002). An adjusted hazard ratio of 2.14 (95% CI=1.04, 4.47, p=0.041) for incident diabetes was observed among participants persistently reporting emotional distress compared with those persistently denying it. CONCLUSIONS: Sustained emotional distress contributes to the development of diabetes among young and apparently healthy men in a time-dependent manner. These findings warrant awareness by primary caregivers when stratifying diabetes risk. PMID- 26810357 TI - Support for Tanning Bed Control Policies Among Female University Students. PMID- 26810359 TI - Strategic level proton therapy patient admission planning: a Markov decision process modeling approach. AB - A relatively new consideration in proton therapy planning is the requirement that the mix of patients treated from different categories satisfy desired mix percentages. Deviations from these percentages and their impacts on operational capabilities are of particular interest to healthcare planners. In this study, we investigate intelligent ways of admitting patients to a proton therapy facility that maximize the total expected number of treatment sessions (fractions) delivered to patients in a planning period with stochastic patient arrivals and penalize the deviation from the patient mix restrictions. We propose a Markov Decision Process (MDP) model that provides very useful insights in determining the best patient admission policies in the case of an unexpected opening in the facility (i.e., no-shows, appointment cancellations, etc.). In order to overcome the curse of dimensionality for larger and more realistic instances, we propose an aggregate MDP model that is able to approximate optimal patient admission policies using the worded weight aggregation technique. Our models are applicable to healthcare treatment facilities throughout the United States, but are motivated by collaboration with the University of Florida Proton Therapy Institute (UFPTI). PMID- 26810358 TI - Efficacy of an Intervention to Alter Skin Cancer Risk Behaviors in Young Adults. AB - INTRODUCTION: Skin cancer is the most common cancer, and its incidence is increasing. Young adults expose themselves to large amounts of ultraviolet radiation (UV) and engage in minimal skin protection, which increases their risk. Internet interventions are effective in modifying health behaviors and are highly disseminable. The current study's purpose was to test an Internet intervention to decrease UV exposure and increase skin protection behavior among young adults. STUDY DESIGN: RCT conducted in 2014, with data analyzed in 2015. SETTING/PARTICIPANTS: A national sample of adults aged 18-25 years at moderate to high risk of developing skin cancer by a self-report measure was recruited online. INTERVENTION: Participants were randomized to one of three intervention conditions: assessment only, the website of a skin cancer organization, or a tailored interactive multimedia Internet intervention program (UV4.me) based on the Integrative Model of Behavioral Prediction. MAIN OUTCOME MEASURES: Self reported overall UV exposure and skin protection assessed at 3 and 12 weeks after baseline. Secondary outcomes were self-reported intentional and incidental UV exposure, sunburns, sunscreen use, and skin cancer screening. RESULTS: For the intervention arm, there were significant decreases in UV exposure and increases in skin protection at both follow-up time points compared with the assessment only condition (p<0.001). The effect sizes (Cohen's d) comparing the experimental and assessment-only arm for exposure behaviors were 0.41 at 3-week follow-up and 0.43 at 12-week follow-up. The effect sizes for protection behaviors were 0.41 at 3-week follow-up and 0.53 at 12-week follow-up. The control condition was not significantly different from the assessment only condition. All three conditions exhibited decreased exposure and increased protection at both follow-ups (p<0.01), but the effect was much stronger in the intervention group. Secondary outcomes were generally also significantly improved in the intervention condition compared with the other conditions. CONCLUSIONS: This is the first published report describing the results of an RCT of an Internet intervention to modify skin cancer risk behaviors among young adults. The UV4.me intervention significantly improved self-reported skin cancer prevention behaviors. Future research will investigate mechanisms of change and approaches for dissemination. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT02147080. PMID- 26810362 TI - Online Self-Affirmation Increases Fruit and Vegetable Consumption in Groups at High Risk of Low Intake. AB - BACKGROUND: This study tested the efficacy of self-affirmation in promoting fruit and vegetable consumption in a sample of participants comprising two groups at high risk of low consumption: young adults and mothers of school-aged children with low social economic status (SES). METHODS: Baseline fruit and vegetable consumption was recorded for 85 participants (n = 26 mothers with low SES). Following randomisation to condition (Self-Affirmed or Non-Affirmed), participants viewed targeted, online, health recommendations about fruit and vegetable consumption. Fruit and vegetable intake was reported online every day for the following seven days. RESULTS: Self-affirmed participants reported consuming significantly more portions of fruit and vegetables (SA M = 3.96, NA M = 2.81). Analyses of simple slopes indicated that the effect was greatest amongst lowest baseline consumers. CONCLUSIONS: The findings demonstrate the efficacy of self-affirmation in increasing fruit and vegetable consumption in individuals who are at risk of having a low intake and whose consumption put them at the greatest risk of negative health outcomes. Application of these findings could help to reduce health care costs, through the use of cost-effective online interventions and reductions in treatment costs. Further research is needed to capitalise on the increased tailoring that online intervention allows in order to optimise the effects of self-affirmation. PMID- 26810363 TI - Comparison of the result of consolidative technique otoplasty and incisionless otoplasty in the repairs of prominent ears. AB - We aimed to compare the long-term results of complications of consolidative technique otoplasty (CTO) and incisionless otoplasty (IO). The study consists of 156 patients who were operated between 2006 and 2015. According to surgical techniques, these patients were divided into two groups as IO group and CTO group. The distance between the head and the ear was assessed by measuring the four points preoperatively and postoperatively (SUP: most superior helical point, SCA: superior conchal attachment, ICA: inferior conchal attachment, and lobule). Early and late postoperative complications, operative time were recorded. 128 ears in IO group, 163 ears in CTO group were prominent. When postoperative SUP, SCA, ICA, lobule values for right and left ears in both groups were statistically evaluated, it was found that CTO technique has led to significantly greater improvement compared to the IO technique (p < 0.001). The success rate in IO technique and CTO technique was 72 and 96 %, respectively. Early complications were similar in both groups. The late period complication determined much more frequently was seen in the IO group. Concerning operative time, it was identified as significantly lower in the IO group (p < 0.001). The early-term outcomes of both techniques were similar; however, the complication rates due to suture material and needed for revision in IO technique were higher whereas CTO technique was more permanent with lower complication risks. PMID- 26810365 TI - Bronsted acid mediated N-O bond cleavage for alpha-amination of ketones through the aromatic nitroso aldol reaction. AB - A Bronsted acid mediated N-O bond cleavage for alpha-amination of ketones has been developed through the nitroso aldol reaction of less-reactive aromatic nitroso compounds and silyl enol ethers having a disilane (-SiMe2TMS) backbone. This transformation is operationally simple and scalable, offering structurally diverse alpha-amino ketones in high yields (up to 98%) with complete regioselectivity. It represents a mechanistically unique and rare example of a metal-free N-O bond cleavage process. PMID- 26810364 TI - Post Roux-en-Y gastric bypass complications: A comparative study assessing the clinical effectiveness of oesophagogastroduodenoscopy and oral-contrast swallow. AB - INTRODUCTION: Anastomotic strictures at the gastrojejunal anastomosis have been reported to occur in 3-20% of patients following a Roux-en-Y gastric bypass (RYGB). Patients commonly present with dysphagia, vomiting and post-prandial pain. Clearly using the appropriate investigations to diagnose the potential complications have both clinical and economical benefits. The reported study compared whether Oesophagogastroduodenoscopy (OGD) or oral-contrast swallow should be employed in patient presenting with post-operative complications following RYGB. METHODS: A retrospective study was conducted on 112 patients between 2008 and 2012; at a level 4 bariatric surgery hospital. Patients who had >=1 OGD to investigate a post-operative complication were included for analysis. Oral-contrast swallow radiology reports performed <28 days prior to an OGD were included for analysis. Patient demographics, OGD, oral-contrast swallow and additional interventions reports were collated from electronic records, pathology and radiology results. RESULTS: 112 patients underwent 1 or more OGD. 75% (n = 67) of patients were diagnosed with a post-operative complication with the most common, 51% (n = 57) being a gastrojejunal anastomotic stricture. 82% (n = 47) of patients presented with dysphagia + - vomiting prior to the diagnosis of gastrojejunal anastomotic strictures. 96% (n = 55) of patients with gastrojejunal anastomotic strictures were successfully treated with balloon dilation. 48% (n = 54) of patients had an oral-contrast swallow as a first line investigation for post-operative symptoms prior to the OGD. 15% (n = 8) of oral-contrast swallow were reported with a significant pathology, with only 1 stricture identified. 70% (n = 38) of oral-contrast swallows reported as normal had a pathology identified at OGD, including 28 strictures. CONCLUSION: We recommend that an OGD should be performed in patients presenting with symptoms consistent with a stricture following RYGB. The urgency of the OGD will be dictated by clinical correlation. The use of a water-soluble contrast swallow should be reserved for a suspected anastomotic leak. PMID- 26810366 TI - Effective Synthesis of Fluorescently Labeled Morpholino Nucleoside Triphosphate Derivatives. AB - Morpholino nucleoside triphosphates (A, U, G, C, T) bearing the active functional amino group tethered to morpholine residue and their fluorescently labeled derivatives were synthesized. All compounds were characterized by (1)H, (13)C, and (31)P NMR, and mass spectrometry. A possibility of using fluorescently labeled morpholino nucleoside triphosphates as chain terminators in DNA sequencing is discussed. PMID- 26810368 TI - Public Health Innovations on the Way to Interruption of Poliovirus Transmission in Nigeria. PMID- 26810367 TI - Recent advances in the development of vaccines against ricin. AB - Several promising subunit vaccines against ricin toxin (RT) have been developed during the last decade and are now being tested for safety and immunogenicity in humans and for efficacy in nonhuman primates. The incentive to develop a preventive vaccine as a countermeasure against RT use as a bioweapon is based on the high toxicity of RT after aerosol exposure, its environmental stability, abundance, and ease of purification. RT is the second most lethal biological toxin and is considered a "universal toxin" because it can kill all eukaryotic cells through binding to ubiquitous cell surface galactosyl residues. RT has two subunits conjoined by a single disulfide linkage: RTB, which binds galactosyl residues and RTA which enzymatically inactivates ribosomes intracellularly by cleavage ribosomal RNA. Attenuation of toxicity by elimination of the active site or introduction of other structural mutations of RTA has generated two similar clinical subunit vaccine candidates which induce antibodies in both humans and nonhuman primates. In rhesus macaques, inhaled RT causes rapid lung necrosis and fibrosis followed by death. After parenteral vaccination with RTA vaccine, macaques can be protected against aerosol RT exposure, suggesting that circulating antibodies can protect lung mucosa. Vaccination induces RT neutralizing antibodies, the most likely correlate of protection. Macaques responded to conformational determinants in an RTA vaccine formulation, indicating preservation of RTA structure during initial manufacture. Comparative mapping studies have also demonstrated that macaques and humans recognize the same epitopes, significant in the study of macaques as a model during development of vaccines which cannot be tested for efficacy in humans. PMID- 26810369 TI - Oral Typhoid Vaccination With Live-Attenuated Salmonella Typhi Strain Ty21a Generates Ty21a-Responsive and Heterologous Influenza Virus-Responsive CD4+ and CD8+ T Cells at the Human Intestinal Mucosa. AB - BACKGROUND: Oral vaccination with live-attenuated Salmonella Typhi strain Ty21a is modestly efficacious, but the mechanisms of protection are currently unknown. While humoral and cellular immune responses are well described in peripheral blood, the cellular response at the intestinal mucosa has never been directly assessed. METHODS: We vaccinated healthy adults with Ty21a and assessed humoral and cellular immunity in vaccinated volunteers and controls after 18 days. Immunoglobulin levels were assessed in peripheral blood by an enzyme-linked immunosorbent assay. Cellular responses were assessed in peripheral blood and at the duodenal and colonic mucosa by flow cytometry. RESULTS: We demonstrate the generation of Ty21a-responsive and heterologous influenza virus-responsive CD4(+) and CD8(+) T cells at the duodenal mucosa. All duodenal responses were consistently correlated, and no responses were observed at the colonic mucosa. Peripheral anti-lipopolysaccharide immunoglobulin G and immunoglobulin A responses were significantly correlated with duodenal responses. The assessment of integrin beta7 expression intensity among peripheral and duodenal T-cell subsets revealed varied capacities for mucosal homing and residence. CONCLUSIONS: The breadth of duodenal cellular responses was not reflected peripherally. The direct evaluation of mucosal immune defense may yield functional correlates of protection and could provide insight into mechanisms that may be manipulated to enhance vaccine immunogenicity. PMID- 26810370 TI - Protein Acetylation Is Involved in Salmonella enterica Serovar Typhimurium Virulence. AB - Salmonella causes a range of diseases in different hosts, including enterocolitis and systemic infection. Lysine acetylation regulates many eukaryotic cellular processes, but its function in bacteria is largely unexplored. The acetyltransferase Pat and NAD(+)-dependent deacetylase CobB are involved in the reversible protein acetylation in Salmonella Typhimurium. Here, we used cell and animal models to evaluate the virulence of pat and cobB deletion mutants in S. Typhimurium and found that pat is critical for bacterial intestinal colonization and systemic infection. Next, to understand the underlying mechanism, genome-wide transcriptome was analyzed. RNA sequencing data showed that the expression of Salmonella pathogenicity island 1 (SPI-1) is partially dependent on pat In addition, we found that HilD, a key transcriptional regulator of SPI-1, is a substrate of Pat. The acetylation of HilD by Pat maintained HilD stability and was essential for the transcriptional activation of HilA. Taken together, these results suggest that a protein acetylation system regulates SPI-1 expression by controlling HilD in a posttranslational manner to mediate S. Typhimurium virulence. PMID- 26810371 TI - Oxytocin inhibits ethanol consumption and ethanol-induced dopamine release in the nucleus accumbens. AB - Alcohol (EtOH) is one of the most widely abused recreational drugs and is arguably the most harmful. However, current treatment options for alcohol-use disorders generally have limited efficacy and poor uptake in the community. In this context, the neuropeptide oxytocin (OXT) has emerged as a promising potential treatment option for a number of substance-use disorders, including alcoholism. The utility of OXT in reducing consumption of and craving for a wide range of substances may lie in its ability to modulate drug-induced neurochemical effects within the mesolimbic dopamine pathway. However, the impact of OXT on EtOH actions in this pathway has yet to be explored. Here, we reveal that an acute intracerebroventricular (icv) infusion of OXT (1 ug/5 ul) attenuated voluntary EtOH (20 percent) self-administration after chronic intermittent access to EtOH for 59 days (28 drinking sessions) in male Wistar rats. Next, we demonstrated that an acute intraperitoneal (ip) injection of EtOH (1.5 g/kg, 15 percent w/v) increased dopamine release within the nucleus accumbens in both EtOH naive rats and rats that had received 10 daily ip injections of EtOH. Icv OXT completely blocked the EtOH-induced dopamine release in both EtOH-naive and chronically treated rats. The attenuation of EtOH-induced dopamine release by OXT may help to explain the reduced EtOH self-administration observed following icv OXT infusion. PMID- 26810374 TI - Cortical Cystic Necrosis in Wilson Disease. PMID- 26810373 TI - Where do we stand in trial readiness for autosomal recessive limb girdle muscular dystrophies? AB - Autosomal recessive limb girdle muscular dystrophies (LGMD2) are a group of genetically heterogeneous diseases that are typically characterised by progressive weakness and wasting of the shoulder and pelvic girdle muscles. Many of the more than 20 different conditions show overlapping clinical features with other forms of muscular dystrophy, congenital, myofibrillar or even distal myopathies and also with acquired muscle diseases. Although individually extremely rare, all types of LGMD2 together form an important differential diagnostic group among neuromuscular diseases. Despite improved diagnostics and pathomechanistic insight, a curative therapy is currently lacking for any of these diseases. Medical care consists of the symptomatic treatment of complications, aiming to improve life expectancy and quality of life. Besides well characterised pre-clinical tools like animal models and cell culture assays, the determinants of successful drug development programmes for rare diseases include a good understanding of the phenotype and natural history of the disease, the existence of clinically relevant outcome measures, guidance on care standards, up to date patient registries, and, ideally, biomarkers that can help assess disease severity or drug response. Strong patient organisations driving research and successful partnerships between academia, advocacy, industry and regulatory authorities can also help accelerate the elaboration of clinical trials. All these determinants constitute aspects of translational research efforts and influence patient access to therapies. Here we review the current status of determinants of successful drug development programmes for LGMD2, and the challenges of translating promising therapeutic strategies into effective and accessible treatments for patients. PMID- 26810375 TI - Ebola outbreak exposed major weakness in UK handling of health emergencies. PMID- 26810376 TI - First Clinical Experience With Thermal-Sprayed Silver Oxide-Containing Hydroxyapatite Coating Implant. AB - BACKGROUND: Prosthetic joint infection is a serious complication of implant therapy. To prevent prosthetic joint infection, we previously reported the features of silver oxide-containing hydroxyapatite (Ag-HA), which was prepared by mixing silver (a metal with antimicrobial activity) with HA. In this study, we evaluated the potential issues of total hip arthroplasty (THA) with an Ag-HA coated implant. METHODS: We prepared an implant for THA that was coated with Ag HA. In this study, the implant contained silver at a maximum quantity of 2.9 mg/implant. In this prospective interventional study, we performed THA with this implant in 20 patients and investigated the effects of silver. RESULTS: Blood silver levels peaked at 2 weeks after THA and gradually decreased thereafter. The highest blood silver level recorded during the postoperative follow-up was 6.0 ng/mL, which was within the normal range. The Harris Hip Scores increased in all cases, and activities of daily living improved markedly after THA with Ag-HA coated implants. Implant failure was absent on radiography. No adverse reaction to silver was noted, and argyria was not observed in any case. No patients have developed infection after surgery. CONCLUSION: This is the first clinical study of Ag-HA-coated implants in THA. Our Ag-HA-coated implants markedly improved patients' activities of daily living without causing any adverse reactions attributable to silver in the human body. Ag-HA is expected to reduce postoperative infections and prevent decreased quality of life in patients undergoing prosthetic arthroplasty, thus leading to more favorable outcomes. PMID- 26810377 TI - Esophageal varices: Stage-dependent treatment algorithm. PMID- 26810378 TI - Evaluating a Pay-for-Performance Program for Medicaid Children in an Accountable Care Organization. AB - IMPORTANCE: Pay for performance (P4P) is a mechanism by which purchasers of health care offer greater financial rewards to physicians for improving processes or outcomes of care. To our knowledge, P4P has not been studied within the context of a pediatric accountable care organization (ACO). OBJECTIVE: To determine whether P4P promotes pediatric performance improvement in primary care physicians. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted from January 1, 2010, to December 31, 2013. A differences-in differences design was used to test whether P4P improved physician performance in an ACO serving Medicaid children. Data were obtained from 2966 physicians and 323,812 patients. Three groups of physicians were identified: (1) community physicians who received the P4P incentives, (2) nonincentivized community physicians, and (3) nonincentivized physicians employed at a hospital. INTERVENTION: Pay for performance. MAIN OUTCOMES AND MEASURES: Healthcare Effectiveness Data Information Set measure rates for preventive care, chronic care, and acute care primary care services. We examined 21 quality measures, 14 of which were subject to P4P incentives. RESULTS: There were 203 incentivized physicians, 2590 nonincentivized physicians, and 173 nonincentivized hospital physicians. Among them, the incentivized community physicians had greater improvements in performance than the nonincentivized community physicians on 2 of 2 well visits (largest difference was for adolescent well care: odds ratio, 1.05; 99.88% CI, 1.02-1.08), 3 of 10 immunization-incentivized measures (largest difference was for inactivated polio vaccine: odds ratio, 1.14; 99.88% CI, 1.07 1.21), and 2 nonincentivized measures (largest difference was for rotavirus: odds ratio, 1.11; 99.88% CI, 1.04-1.18). The employed physician group at the hospital had greater improvements in performance than the incentivized community physicians on 8 of 14 incentivized measures and 1 of 7 nonincentivized measures (largest difference was for hepatitis A vaccine: odds ratio, 0.34; 99.88% CI, 0.31-0.37). CONCLUSIONS AND RELEVANCE: Pay for performance resulted in modest changes in physician performance in a pediatric ACO, but other interventions at the disposal of the ACO may have been even more effective. Further research is required to find methods to enhance quality improvements across large distributed pediatric health systems. PMID- 26810380 TI - Relationship between early growth and CVD risk factors in adolescents. AB - Low birth weight and a rapid weight gain in early childhood may lead to an increased risk for developing cardiovascular disease later in life, such as hypertension and dyslipidaemia. In this study, we examined the associations between size at birth, relative weight gain in infancy and childhood with specific cardiovascular disease risk factors in early adulthood. Adolescents (n=1935) from the Birth to Twenty plus (BT20+) cohort were included in the analysis. The following were treated as exposure variables: weight at birth, and relative conditional weight gain (CW), independent of height, between ages 0-24 months and 24-48 months. Outcomes were serum lipids and body composition variables at age 18 years. After adjusting for sex and other confounders, early life exposures were not associated with adolescent lipid profile. Following adjustment for sex and height (body size), birth weight [beta=0.704 (0.40, 1.01)], CW 0-24 [beta=1.918 (1.56, 2.28)] and CW24-48 [beta=1.485 (1.14, 1.82)] accounted for 48% of the variance in fat mass. However, birth weight [beta=0.773 (0.54, 1.01)], CW 0-24 [beta=1.523 (1.24, 1.80)] and CW24-48 [beta=1.226 (0.97, 1.49)] were also positively predicted and accounted for 71% of the variance in fat mass in adolescence (P<0.05). Our data suggests that birth weight and weight gain during infancy and early childhood independent of linear growth are related to adolescent body composition but not blood lipid profiles in an urban African population. PMID- 26810381 TI - How early L2 children perform on Italian clinical markers of SLI: A study of clitic production and nonword repetition. AB - Early second language (EL2) learners generally perform more poorly than monolinguals in specific language domains, presenting similarities with children affected by specific language impairment (SLI). As a consequence, it can be difficult to correctly diagnose this disorder in EL2 children. The current study investigated the performance of 120 EL2 and 40 age-matched monolingual children in object clitic production and nonword repetition, which are two sensitive clinical markers of SLI in Italian. Results show that EL2 children underperform in comparison to monolinguals in the clitic task. However, in contrast to what is reported on Italian-speaking children with SLI, EL2 children tend not to omit clitics but instead produce the incorrect form, committing agreement errors. No differences are found between EL2 and monolingual children on nonword repetition. These results suggest that, at least in Italian, EL2 children only superficially resemble children with SLI and, on closer inspection, present a qualitatively and quantitatively different linguistic profile. PMID- 26810383 TI - Economic evaluations of psychosocial interventions in cancer: a systematic review. AB - OBJECTIVE: Although the effectiveness of many psychosocial interventions for people with cancer has been established, one barrier to implementation in routine clinical care is a lack of data on cost-effectiveness. We conducted a systematic review to assess the cost-effectiveness of psychosocial interventions for improving psychological adjustment among people with cancer. METHODS: A systematic review of the literature, study appraisal and narrative synthesis. RESULTS: Eight studies involving 1668 patients were identified. Four of these reported outcomes in a cost per quality adjusted life year (QALY) framework. Six studies reported psychosocial interventions to be cost-effective for improving health-related quality of life, mood, pain, distress or fear of cancer progression, compared with usual care. Of the six psychosocial interventions identified as cost-effective, three were cognitive-behavioural therapy-based interventions, one was a nurse-delivered telephone follow-up plus educational group programme, one was a group-based exercise and psychosocial intervention and one was a series of 10 face-to-face or telephone-based individual support sessions delivered by a nurse. The quality of studies assessed according to the Consensus Health Economic Criteria-list criteria was good overall; however, some studies were limited by their choice of outcome measure and omission of important categories of costs. CONCLUSIONS: Several psychosocial interventions, particularly those based on cognitive-behavioural therapy, have been demonstrated to represent good value for money in cancer care. Future research should include a clear definition of the economic question, inclusion of all relevant costs, and consideration of utility-based quality of life measures for QALY estimation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26810384 TI - Corosolic acid analogue, a natural triterpenoid saponin, induces apoptosis on human hepatocarcinoma cells through mitochondrial pathway in vitro. AB - Context 2a,-3a,-24-Trihydroxyurs-12-en-28-oic acid (TEO, a corosolic acid analogue) is a triterpenoid saponin isolated from Actinidia valvata Dunn (Actinidiaceae), a well-known traditional Chinese medicine. Objective This study investigated the anti-proliferation and inducing apoptosis effects of TEO in three human hepatocellular carcinoma (HCC) cell lines. Materials and methods Cytotoxic activity of TEO was determined by the MTT assay at various concentrations from 2.5 to 40 MUg/mL in BEL-7402, BEL-7404 and SMMC-7721 cell lines. Cell morphology was assessed by acridine orange/ethidium bromide and 4'-6 diamidino-2-phenylindole dihydrochloride staining and fluorescence microscopy. Cell-cycle distribution and DNA damage were determined by flow cytometry and comet assay. Mitochondrial dysfunction was assessed by JC-1 staining and transmission electron microscopy. Apoptosis changes were explored by Western blot, TNF-alpha and caspase-3, -8, -9 assays. Results TEO exhibited inhibition effects on BEL-7402, BEL-7404 and SMMC-7721 cells treated for 24 h, the IC50 values were 34.6, 30.8 and 30.5 MUg/mL, respectively. TEO (40 MUg/mL)-treated three cell lines increased by more than 21% in the G1 phase and presented the morphological change and DNA damage. TEO also declined the mitochondrial membrane potential and altered mitochondrial ultra-structure. Furthermore, caspase-3, caspase-8, caspase-9 and TNF-alpha were also activated. Mechanism investigation showed that TEO could decrease anti-apoptotic Bcl-2 protein expression, increase proapoptotic Bax and Bid proteins expressions and increase Bax/Bcl-2 ratio. Conclusion Our results demonstrate for the first time that TEO inhibited growth of HCC cell lines and induced G1 phase arrest. Moreover, proapoptotic effects of TEO were mediated through the activation of TNF-alpha, caspases and mitochondrial pathway. PMID- 26810387 TI - Gate tunable WSe2-BP van der Waals heterojunction devices. AB - Due to the weak screening effect, the concentration and type of charge carriers in 2D semiconductor heterostructures can be effectively tuned by electrostatic gating, enabling us to realize different types of heterojunctions in a single device. Such 'type tunable' properties are useful for designing novel electrical or optoelectrical devices. Here, we demonstrate a 'type tunable' heterojunction device construct with two pieces of ambipolar 2D semiconductors: WSe2 and black phosphorus (BP). This heterojunction could be tuned to either the p-p junction or n-n junction by gate modulation. The p-p junction shows a large current rectification ratio while the n-n junction shows a negligible current rectification ratio, indicating a large valence band offset and a small conduction band offset at the WSe2/BP interface. In the optoelectrical measurements, we found the amplitude and even the polarity of photocurrent could be modulated by electrostatic gating. Our study could further enhance the understanding of designing devices based on these 'type tunable' van der Waals heterojunctions. Moreover, the properties of the WSe2/BP interface were also experimentally identified through the electrical and optoelectrical measurements in our study. PMID- 26810389 TI - "You kind of want to fix it don't you?" Exploring general practice trainees' experiences of managing patients with medically unexplained symptoms. AB - BACKGROUND: Much of a General Practitioner's (GP) workload consists of managing patients with medically unexplained symptoms (MUS). GP trainees are often taking responsibility for looking after people with MUS for the first time and so are well placed to reflect on this and the preparation they have had for it; their views have not been documented in detail in the literature. This study aimed to explore GP trainees' clinical and educational experiences of managing people presenting with MUS. METHOD: A mixed methods approach was adopted. All trainees from four London GP vocational training schemes were invited to take part in a questionnaire and in-depth semi-structured interviews. The questionnaire explored educational and clinical experiences and attitudes towards MUS using Likert scales and free text responses. The interviews explored the origins of these views and experiences in more detail and documented ideas about optimising training about MUS. Interviews were analysed using the framework analysis approach. RESULTS: Eighty questionnaires out of 120 (67%) were returned and a purposive sample of 15 trainees interviewed. Results suggested most trainees struggled to manage the uncertainty inherent in MUS consultations, feeling they often over-investigated or referred for their own reassurance. They described difficulty in broaching possible psychological aspects and/or providing appropriate explanations to patients for their symptoms. They thought that more preparation was needed throughout their training. Some had more positive experiences and found such consultations rewarding, usually after several consultations and developing a relationship with the patient. CONCLUSION: Managing MUS is a common problem for GP trainees and results in a disproportionate amount of anxiety, frustration and uncertainty. Their training needs to better reflect their clinical experience to prepare them for managing such scenarios, which should also improve patient care. PMID- 26810390 TI - A Vacuum Ultraviolet Absorption Array Spectrometer as a Selective Detector for Comprehensive Two-Dimensional Gas Chromatography: Concept and First Results. AB - Fast and selective detectors are very interesting for comprehensive two dimensional gas chromatography (GC * GC). This is particularly true if the detector system can provide additional spectroscopic information on the compound structure and/or functionality. Other than mass spectrometry (MS), only optical spectroscopic detectors are able to provide selective spectral information. However, until present the application of optical spectroscopy technologies as universal detectors for GC * GC has been restricted mainly due to physical limitations such as insufficient acquisition speed or high detection limits. A recently developed simultaneous-detection spectrometer working in the vacuum ultraviolet (VUV) region of 125-240 nm overcomes these limitations and meets all the criteria of a universal detector for GC * GC. Peak shape and chromatographic resolution is preserved and unique spectral information, complementary to mass spectrometry data, is gained. The power of this detector is quickly recognized as it has the ability to discriminate between isomeric compounds or difficult to separate structurally related isobaric species; thus, it provides additional selectivity. A further promising feature of this detector is the data analysis concept of spectral filtering, which is accomplished by targeting special electronic transitions that allows for a fast screening of GC * GC chromatograms for designated compound classes. PMID- 26810392 TI - Bringing High-Rate, CO2-Based Microbial Electrosynthesis Closer to Practical Implementation through Improved Electrode Design and Operating Conditions. AB - The enhancement of microbial electrosynthesis (MES) of acetate from CO2 to performance levels that could potentially support practical implementations of the technology must go through the optimization of key design and operating conditions. We report that higher proton availability drastically increases the acetate production rate, with pH 5.2 found to be optimal, which will likely suppress methanogenic activity without inhibitor addition. Applied cathode potential as low as -1.1 V versus SHE still achieved 99% of electron recovery in the form of acetate at a current density of around -200 A m(-2). These current densities are leading to an exceptional acetate production rate of up to 1330 g m(-2) day(-1) at pH 6.7. Using highly open macroporous reticulated vitreous carbon electrodes with macropore sizes of about 0.6 mm in diameter was found to be optimal for achieving a good balance between total surface area available for biofilm formation and effective mass transfer between the bulk liquid and the electrode and biofilm surface. Furthermore, we also successfully demonstrated the use of a synthetic biogas mixture as carbon dioxide source, yielding similarly high MES performance as pure CO2. This would allow this process to be used effectively for both biogas quality improvement and conversion of the available CO2 to acetate. PMID- 26810391 TI - Three-year randomized study of manual and power toothbrush effects on pre existing gingival recession. AB - AIM: To compare long-term effects of brushing with an oscillating-rotating power toothbrush or an ADA reference manual toothbrush on pre-existing gingival recession. MATERIALS AND METHODS: In this controlled, prospective, single-blind, parallel-group study, healthy subjects with pre-existing recession were randomized and brushed with a power toothbrush (n = 55) or an ADA reference manual toothbrush (n = 54) for a 3-year study period. Subjects were required to brush their teeth twice daily for 2 min. using a standard fluoride toothpaste. During the study, subjects were assessed for clinical attachment loss and probing pocket depths to the nearest mm at six sites per tooth by the same calibrated examiner. Gingival recession was calculated at pre-existing sites as the difference between clinical attachment loss and probing pocket depths. Hard and soft oral tissues were examined to assess safety. RESULTS: After 35 +/- 2 months, mean gingival recession did not differ significantly between groups, but was significantly reduced from baseline (p < 0.001), from 2.35 +/- 0.35 mm to 1.90 +/ 0.58 mm in the power and from 2.26 +/- 0.31 mm to 1.81 +/- 0.66 mm in the manual group. CONCLUSIONS: Gingival recession in subjects with pre-existing recession was significantly reduced after 3 years of brushing with either a power or manual toothbrush. PMID- 26810393 TI - Cascade: an RNA-seq visualization tool for cancer genomics. AB - BACKGROUND: Cancer genomics projects are producing ever-increasing amounts of rich and diverse data from patient samples. The ability to easily visualize this data in an integrated an intuitive way is currently limited by the current software available. As a result, users typically must use several different tools to view the different data types for their cohort, making it difficult to have a simple unified view of their data. RESULTS: Here we present Cascade, a novel web based tool for the intuitive 3D visualization of RNA-seq data from cancer genomics experiments. The Cascade viewer allows multiple data types (e.g. mutation, gene expression, alternative splicing frequency) to be simultaneously displayed, allowing a simplified view of the data in a way that is tuneable based on user specified parameters. The main webpage of Cascade provides a primary view of user data which is overlaid onto known biological pathways that are either predefined or added by users. A space-saving menu for data selection and parameter adjustment allows users to access an underlying MySQL database and customize the features presented in the main view. CONCLUSIONS: There is currently a pressing need for new software tools to allow researchers to easily explore large cancer genomics datasets and generate hypotheses. Cascade represents a simple yet intuitive interface for data visualization that is both scalable and customizable. PMID- 26810394 TI - Non-medical financial burden in tuberculosis care: a cross-sectional survey in rural China. AB - BACKGROUND: Treatment of tuberculosis (TB) in China is partially covered by national programs and health insurance schemes, though TB patients often face considerable medical expenditures. For some, especially those from poorer households, non-medical costs, such as transport, accommodation, and nutritional supplementation may be a substantial additional burden. In this article we aim to evaluate these non-medical costs induced by seeking TB care using data from a large scale cross-sectional survey. METHODS: A total of 797 TB cases from three cities were randomly selected using a stratified cluster sampling design. Inpatient medical costs, outpatient medical costs, and direct non-medical costs related to TB treatment were collected using in-person interviews by trained interviewers. Mean and median non-medical costs for different sub-groups were calculated and compared using Kruskal-Wallis and Mann-Whitney U tests. Regression analysis was conducted to assess the influence of different patient characteristics on total non-medical cost. RESULTS: The median non-medical cost was RMB 1429, with interquartile range RMB 424-2793. The median non-medical costs relating to inpatient treatment, outpatient treatment, and additional nutrition supplementation were RMB 540, 91, and 900, respectively. Of the 797 cases, 20 % reported catastrophic expenditure on non-medical costs. Statistically significant differences were detected between different cities, age groups, geographical locations, inpatient/outpatient care, education levels and family income groups. CONCLUSIONS: Non-medical costs relating to TB treatment are a serious financial burden for many TB patients. Financial assistance that can limit this burden is urgently needed during the treatment period, especially for the poor. PMID- 26810395 TI - Wang-Landau simulation of Go model molecules. AB - Go-like models are one of the oldest protein modeling concepts in computational physics and have proven their value over and over for forty years. The essence of a Go model is to define a native contact matrix for a well-defined low-energy polymer configuration, e.g., the native state in the case of proteins or peptides. Many different potential shapes and many different cut-off distances in the definition of this native contact matrix have been proposed and applied. We investigate here the physical consequences of the choice for this cut-off distance in the Go models derived for a square-well tangent sphere homopolymer chain. For this purpose we are performing flat-histogram Monte Carlo simulations of Wang-Landau type, obtaining the thermodynamic and structural properties of such models over the complete temperature range. Differences and similarities with Go models for proteins and peptides are discussed. PMID- 26810396 TI - Effects of viscoelasticity on droplet dynamics and break-up in microfluidic T Junctions: a lattice Boltzmann study. AB - The effects of viscoelasticity on the dynamics and break-up of fluid threads in microfluidic T-junctions are investigated using numerical simulations of dilute polymer solutions at changing the Capillary number (Ca), i.e. at changing the balance between the viscous forces and the surface tension at the interface, up to Ca ~ 3*10(-2). A Navier-Stokes (NS) description of the solvent based on the lattice Boltzmann models (LBM) is here coupled to constitutive equations for finite extensible non-linear elastic dumbbells with the closure proposed by Peterlin (FENE-P model). We present the results of three-dimensional simulations in a range of Ca which is broad enough to characterize all the three characteristic mechanisms of break-up in the confined T-junction, i.e. squeezing, dripping and jetting regimes. The various model parameters of the FENE-P constitutive equations, including the polymer relaxation time tauP and the finite extensibility parameter L2, are changed to provide quantitative details on how the dynamics and break-up properties are affected by viscoelasticity. We will analyze cases with Droplet Viscoelasticity (DV), where viscoelastic properties are confined in the dispersed (d) phase, as well as cases with Matrix Viscoelasticity (MV), where viscoelastic properties are confined in the continuous (c) phase. Moderate flow-rate ratios Q ~ O(1) of the two phases are considered in the present study. Overall, we find that the effects are more pronounced in the case with MV, as the flow driving the break-up process upstream of the emerging thread can be sensibly perturbed by the polymer stresses. PMID- 26810397 TI - Phyllotaxis: a framework for foam topological evolution. AB - Phyllotaxis describes the arrangement of florets, scales or leaves in composite flowers or plants (daisy, aster, sunflower, pinecone, pineapple). As a structure, it is a geometrical foam, the most homogeneous and densest covering of a large disk by Voronoi cells (the florets), constructed by a simple algorithm: Points placed regularly on a generative spiral constitute a spiral lattice, and phyllotaxis is the tiling by the Voronoi cells of the spiral lattice. Locally, neighboring cells are organized as three whorls or parastichies, labelled with successive Fibonacci numbers. The structure is encoded as the sequence of the shapes (number of sides) of the successive Voronoi cells on the generative spiral. We show that sequence and organization are independent of the position of the initial point on the generative spiral, that is invariant under disappearance (T2 of the first Voronoi cell or, conversely, under creation of a first cell, that is under growth. This independence shows how a foam is able to respond to a shear stress, notably through grain boundaries that are layers of square cells slightly truncated into heptagons, pentagons and hexagons, meeting at four-corner vertices, critical points of T1 elementary topological transformations. PMID- 26810398 TI - In Vitro and In Vivo Human Metabolism of Synthetic Cannabinoids FDU-PB-22 and FUB PB-22. AB - In 2014, FDU-PB-22 and FUB-PB-22, two novel synthetic cannabinoids, were detected in herbal blends in Japan, Russia, and Germany and were quickly added to their scheduled drugs list. Unfortunately, no human metabolism data are currently available, making it challenging to confirm their intake. The present study aims to identify appropriate analytical markers by investigating FDU-PB-22 and FUB-PB 22 metabolism in human hepatocytes and confirm the results in authentic urine specimens. For metabolic stability, 1 MUM FDU-PB-22 and FUB-PB-22 was incubated with human liver microsomes for up to 1 h; for metabolite profiling, 10 MUM was incubated with human hepatocytes for 3 h. Two authentic urine specimens from FDU PB-22 and FUB-PB-22 positive cases were analyzed after beta-glucuronidase hydrolysis. Metabolite identification in hepatocyte samples and urine specimens was accomplished by high-resolution mass spectrometry using information-dependent acquisition. Both FDU-PB-22 and FUB-PB-22 were rapidly metabolized in HLM with half-lives of 12.4 and 11.5 min, respectively. In human hepatocyte samples, we identified seven metabolites for both compounds, generated by ester hydrolysis and further hydroxylation and/or glucuronidation. After ester hydrolysis, FDU-PB 22 and FUB-PB-22 yielded the same metabolite M7, fluorobenzylindole-3-carboxylic acid (FBI-COOH). M7 and M6 (hydroxylated FBI-COOH) were the major metabolites. In authentic urine specimens after beta-glucuronidase hydrolysis, M6 and M7 also were the predominant metabolites. Based on our study, we recommend M6 (hydroxylated FBI-COOH) and M7 (FBI-COOH) as suitable urinary markers for documenting FDU-PB-22 and/or FUB-PB-22 intake. PMID- 26810399 TI - A digestive allergic reaction with hypereosinophilia imputable to docetaxel in a breast cancer patient: a case report. AB - BACKGROUND: Hypereosinophilia, defined by an absolute eosinophil count of more than 1500/mm3, is rarely observed in patients treated for cancer, and rarely imputable to anti-cancer agents. Drug-induced hypereosinophilia usually appears within a few weeks of the start of treatment and resolves after discontinuation of the medication. We report here a first case of hypereosinophilia with digestive allergic reaction imputable to docetaxel in a woman treated for breast cancer. CASE PRESENTATION: This patient, with a history of childhood atopic dermatitis and asthma, underwent surgery for breast lobular carcinoma, followed with chemotherapy including 3 cycles of the FEC100 protocol and 3 cycles of docetaxel. Ten days after the second cycle of docetaxel, she had abdominal pain with diarrhea, which increased after the third cycle of docetaxel at the same dose. The blood eosinophil count increased up to 4685/mm(3) at day 92. All biological tests were normal, except elevated seric IgE. The systematic biopsies of the upper and lower digestive tract showed diffuse edema of the lamina propria, lymphocytic infiltrate and CD117-expressing cells both in the epithelium and in the lamina propria. Electron microscopy showed a large number of degranulating mast cells, while the number of tissue eosinophils was small. The blood eosinophil count decreased after day 96, three months after the last injection of docetaxel. After day 182, the hypereosinophilia and symptoms resolved. This spontaneous evolution, the history of atopic dermatitis and asthma, and the negativity of all biological tests performed led us to hypothesize a diagnosis of a systemic digestive Type 1 drug-induced hypersensitivity reaction. Using two validated pharmacovigilance scales, we found that docetaxel had the highest imputability score compared to the other drugs. CONCLUSION: Recognition of allergic reactions imputable to docetaxel is important because it requires the drug to be discontinued. In the difficult setting of anti cancer treatment, if reintroduction of the drug is needed, a close collaboration between oncologists, gastroenterologists and allergologists is required. PMID- 26810400 TI - Homology differences between complete Sacbrood virus genomes from infected Apis mellifera and Apis cerana honeybees in Korea. AB - Sacbrood virus (SBV) represents a serious threat to the health of managed honeybees. We determined four complete SBV genomic sequences (AmSBV-Kor1, AmSBV Kor2, AcSBV-Kor3, and AcSBV-Kor4) isolated from Apis mellifera and Apis cerana in various regions of South Korea. A phylogenetic tree was constructed from the complete genomic sequences of these Korean SBVs (KSBVs) and 21 previously reported SBV sequences from other countries. Three KSBVs (not AmSBV-Kor1) clustered with previously reported Korean genomes, but separately from SBV genomes from other countries. The KSBVs shared 90-98 % identity, and 89-97 % identity with the genomes from other countries. AmSBV-Kor1 was least similar (~90 % identity) to the other KSBVs, and was most similar to previously reported strains AmSBV-Kor21 (97 %) and AmSBV-UK (93 %). Phylogenetic analysis of the partial VP1 region sequences indicated that SBVs clustered by host species and country of origin. The KSBVs were aligned with nine previously reported complete SBV genomes and compared. The KSBVs were most different from the other genomes at the end of the 5' untranslated region and in the entire open reading frame. A SimPlot graph of the VP1 region confirmed its high variability, especially between the SBVs infecting A. mellifera and A. cerana. In this genomic region, SBVs from A. mellifera species contain an extra continuous 51-nucleotide sequence relative to the SBVs from A. cerana. This genomic diversity may reflect the adaptation of SBV to specific hosts, viral cross-infections, and the spatial distances separating the KSBVs from other SBVs. PMID- 26810401 TI - A highly divergent isolate of tomato blistering mosaic virus from Solanum violaefolium. AB - The complete genome of a tymovirus infecting Solanum violaefolium was sequenced. The genome comprised 6284 nt, with a 5'-UTR of 137 nt and a comparatively longer 3'-UTR of 121 nt. Sequence analysis confirmed three ORFs encoding a movement protein, a polyprotein, and a coat protein (CP). The isolate was considered to be the Tomato blistering mosaic virus (ToBMV) based on a CP amino acid sequence identity of 95.3 %. The nucleotide sequence of the complete genome of the S. violaefolium isolate, however, differed markedly from the other two reported ToBMV isolates, with identities of 76.6 and 76.3 %, below one of the demarcation criteria of the genus Tymovirus (overall genome identity of 80 %). No recombination signals were detected in the genome of this isolate. The high identity of the CP amino acid sequence and similar host responses suggest that the S. violaefolium isolate belongs to the same species as the Tomato blistering mosaic virus. The sequence analysis of this ToBMV isolate thus suggests that the demarcation criterion of 80 % overall genome sequence identity in the genus Tymovirus may require revision. PMID- 26810402 TI - Molecular analyses of H3N2 canine influenza viruses isolated from Korea during 2013-2014. AB - Canine influenza A virus (CIV) causes a respiratory disease among dog populations and is prevalent in North America and Asia. Recently, Asian H3N2 CIV infection has been of particular concern, with recent reports related to reassortants with pandemic 2009 strains, direct transmission from a human H3N2, a possibility of H3N2 CIV transmission to other mammals, and even the first outbreak of H3N2 CIVs in North America in April 2015. However, despite these global concerns, our understanding of how influenza A virus transmission impacts the overall populations of H3N2 CIVs remains incomplete. Hence, we investigated the evolutionary history of the most recent two Korean CIV isolates, A/canine/Korea/BD-1/2013 and A/canine/Korea/DG1/2014, along with 57 worldwide CIVs, using comprehensive molecular analyses based on genomic genotyping. This study presents that the new Korean CIV isolates are closely related to the predominantly circulating H3N2 CIVs with genotypes K, G, E, 3B, F, 2D, F, and 1E, carrying several mutations in antigenic and host determinant sites. Also, our findings show that the genome-wide genetic variations within the H3N2 CIVs are low; however, two antigenic protein (HA and NA) analysis demonstrates genetic diversification of the H3N2 CIVs, which evolves independently between Korea and China. PMID- 26810403 TI - Topical corticosteroid has no influence on inflammation or efficacy after ingenol mebutate treatment of grade I to III actinic keratoses (AK): A randomized clinical trial. AB - BACKGROUND: Ingenol mebutate (IngMeb) is approved for treatment of actinic keratoses (AK) and may cause unpredictable local skin responses (LSR). OBJECTIVES: We sought to investigate whether IngMeb-induced LSR, pain, and pruritus could be alleviated with a topical glucocorticoid and, further, to assess efficacy, cosmetic outcome, and patient satisfaction in patients with severe photodamage. METHODS: In this blinded, randomized controlled clinical trial, patients with multiple AK and field cancerization of the face or scalp were treated in 2 areas with IngMeb (0.015%) daily for 3 days. After finalized IngMeb treatment, 1 area was randomized to receive topical clobetasol propionate (0.05%) twice daily for 4 days. Assessments included LSR (0-24; days 1, 4, 8, 15, 57), pain (0-10) and pruritus (0-3; days 1-15), AK clearance (days 15, 57), and cosmetic outcome (0-3; day 57). RESULTS: Clobetasol propionate application had no influence on LSR (P = .939), pain (P = .500), pruritus (P = .312), or AK cure rate (P = .991). Overall, IngMeb cleared 86% of all AK lesions, exerting a therapeutic effect on all AK severity grades; cure rates were 88%, 70%, and 60% for grade I, II, and III AK, respectively. Skin texture improved significantly in remedied areas (2.0 vs 1.0; P < .001); no hypopigmentation, hyperpigmentation, or scarring were observed. LIMITATIONS: These results do not provide safety and efficacy beyond 2 months of follow-up. CONCLUSION: Application of clobetasol propionate does not alleviate IngMeb-induced LSR after 3 days of IngMeb treatment. PMID- 26810404 TI - [Organ donation after circulatory death]. AB - Approximately 17 million inhabitants live in the Netherlands. The number of potential organ donors in 1999 was the lowest in Europe with only 10 donors per million inhabitants. Medical associations, public health services, health insurance companies and the government had to find common solutions in order to improve organ allocation, logistics of donations and to increase the number of transplantations. After a prolonged debate on medical ethical issues of organ transplantation, all participants were able to agree on socio-medico-legal regulations for organ donation and transplantation. In addition to improving the procedure for organ donation after brain death (DBD) the most important step was the introduction of organ donation after circulatory death (DCD). Measures such as the introduction of a national organ donor database, improved information to the public, further education on intensive care units (ICU), guidelines for end of life care on the ICU, establishment of transplantation coordinators on site, introduction of autonomous explantation teams and strict procedures on the course of organ donations, answered many practical issues about logistics and responsibilities for DBD and DCD. In 2014 the number of postmortem organ donations rose to 16.4 per million inhabitants. Meanwhile, up to 60 % of organ donations in the Netherlands originate from a DCD procedure compared to approximately 10 % in the USA. This overview article discusses the developments and processes of deceased donation in the Netherlands after 15 years of experience with DCD. PMID- 26810408 TI - Why brachytherapy boost is the treatment of choice for most women with locally advanced cervical carcinoma? AB - The standard treatment approach for women with locally advanced cervical carcinoma is definitive radiation treatment with concurrent cisplatin chemotherapy. Radiation treatment is typically external beam radiation therapy to the pelvis followed by intracavitary brachytherapy (BT) boost to the cervix. Numerous studies confirmed very successful outcomes with this approach. In recent years, however, the use of BT to boost the cervix in women with cervical carcinoma was reported to be on the decline. With the advent of advanced external beam radiation therapy techniques, few attempts have been made to substitute the BT boost with stereotactic body radiation therapy or intensity-modulated radiation therapy techniques, but there is a lack of prospective data to justify the routine use of these alternate boost techniques. The aim of this review is to highlight the differences between the use of stereotactic body radiation therapy or intensity-modulated radiation therapy, in lieu of intracavitary BT boost in women with locally advanced cervical cancer, and to argue that BT seems to be truly irreplaceable at the present time and with the knowledge and expertise accumulated to date. PMID- 26810405 TI - [Traumatic brain injury]. AB - Since traumatic brain injury is the most common cause of long-term disability and death among young adults, it represents an enormous socio-economic and healthcare burden. As a consequence of the primary lesion, a perifocal brain edema develops causing an elevation of the intracranial pressure due to the limited intracranial space. This entails a reduction of the cerebral perfusion pressure and the cerebral blood flow. A cerebral perfusion deficit below the threshold for ischemia leads to further ischemic lesions and to a progression of the contusion. As the irreversible primary lesion can only be inhibited by primary prevention, the therapy of traumatic brain injury focuses on the secondary injuries. The treatment consists of surgical therapy evacuating the space-occupying intracranial lesion and conservative intensive medical care. Due to the complex pathophysiology the therapy of traumatic brain injury should be rapidly performed in a neurosurgical unit. PMID- 26810406 TI - Nipple reconstruction after implant-based breast reconstruction in radiated patients: A new safe dermal flap. AB - INTRODUCTION: After implant-based breast reconstruction, the nipple reconstruction technique must be carefully chosen, especially in patients with a history of radiotherapy. When the contralateral nipple is not available, using a classical dermal-fat local flap may lead to the implant exposure, and consequently, removal. We describe here a simple nipple reconstruction technique, using a strictly dermal local flap and evaluate its complication rate. PATIENTS AND METHODS: All patients who underwent our technique for nipple reconstruction between January 2012 and April 2015 were included in this retrospective study. We described our surgical technique and noted the occurrence of postoperative complications. RESULTS: Forty-nine nipples, in 47 patients with a history of radiotherapy, were reconstructed with our technique. The mean age was 53 years old (range 27-78 years old). The average time between radiotherapy and nipple reconstruction was 42.5 months (range from 4.6 to 274.8 months). The mean follow up was 30.9 months (range from 6 to 47 months). No implant exposure occurred. Regarding the nipple flap, two partial flap loss and one infection occurred, the whole complication rate was 6.1%. Regarding nipple projection, it was quite low (between 2 and 5 mm) after 6 months, but remained stable. CONCLUSION: Our strictly dermal local flap technique for nipple reconstruction is a safe procedure and represents a good alternative to composite contralateral nipple graft in irradiated patients with an implant-based reconstructed breast. PMID- 26810410 TI - Accuracy of tympanic membrane assessment. PMID- 26810411 TI - Antimicrobial susceptibility testing for feline urinary tract isolates. PMID- 26810414 TI - Cytokeratin 7-positive/cytokeratin 20-negative cecal adenocarcinoma metastatic to the uterine cervix: a case report. AB - BACKGROUND: The vast majority of uterine cervical malignancies are primary carcinomas, and secondary neoplasms that metastasize to the uterine cervix from a distant organ are uncommon. Although relatively rare, metastases to the uterine cervix from a primary colon cancer have been reported. We report a rare case of metastatic carcinoma originating from a cecal adenocarcinoma with an unusual cytokeratin 7/cytokeratin 20 immunophenotype. CASE PRESENTATION: A 74-year-old postmenopausal Japanese woman was referred to our hospital for the evaluation of a uterine tumor. She had a past medical history of cecal cancer and had undergone laparoscopically assisted right hemicolectomy at the age of 69 years. During follow-up, she was found to have elevated levels of the tumor markers carbohydrate antigen 19-9 (179.7 IU/mL) and carcinoembryonic antigen (26.9 MUg/L). Positron emission tomography/computed tomography showed a focus of high 18F-fluorodeoxyglucose uptake in her uterus. Examination of a cervical biopsy found a poorly differentiated adenocarcinoma that was immunopositive for cytokeratin (CK)7 and caudal-related homeobox 2 (CDX2) expression and immunonegative for cytokeratin 20 expression. The patient underwent radical hysterectomy and bilateral salpingo-oophorectomy. Histopathological examination found invasive growth of irregular and atypical ductal hyperplasia. Immunohistochemical staining of the tumor specimen revealed the same immunophenotype as the biopsy specimen. The cecal cancer specimen from her previous surgery was also examined and found to have the same immunophenotype. The histopathological diagnosis was cecal adenocarcinoma metastatic to the uterine cervix. The patient is currently receiving adjuvant chemotherapy and to date is without evidence of recurrent disease. CONCLUSIONS: Our report illustrates the importance of immunohistochemistry for the correct diagnosis of the origin of a uterine cervical adenocarcinoma in a patient with a medical history of colorectal cancer. Re-examination of a previous oncological specimen is critical for cases with a uterine lesion that is difficult to identify as primary or metastatic cancer. PMID- 26810416 TI - Balancing cardiovascular and gastrointestinal risks in patients with osteoarthritis receiving nonsteroidal anti-inflammatory drugs. A summary of guidelines from an international expert group. AB - Over the past 2 decades, extensive research has assessed the use of traditional nonsteroidal anti-inflammatory drugs (NSAIDs), and the newer cyclooxygenase-2 (COX-2) inhibitor drugs, in the treatment of chronic pain syndromes. The proper use of NSAIDs has been the subject of significant debate, bringing together multidisciplinary researchers and clinicians to discuss the risks and benefits of these therapies. Current guidelines discussing the proper use of NSAIDs do not address the issue of the risks of COX-2-selective NSAIDs and nonselective NSAIDs for both the gastrointestinal (GI) and cardiovascular (CV) systems in patients on low-dose aspirin. Accordingly, a multidisciplinary expert group was organized to review the current evidence with the aim of developing statements devoted to guide clinicians in making evidence-based and individualized selections of NSAIDs. This review will discuss and summarize the most recent evidence on this topic to give an insight into the most effective and safest therapeutic options, thus preventing serious adverse CV and GI events. NSAIDs should be used cautiously and as infrequently as possible, with nonpharmacological approaches prescribed first. If the use of NSAIDs is required, the choice should balance the possible CV and GI risks. PMID- 26810417 TI - Imaging of differentiated thyroid carcinoma: (124)I-PET/MRI may not be superior to (124)I-PET/CT. PMID- 26810419 TI - Executive Summary: Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. AB - It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. PMID- 26810418 TI - Gene signature of the post-Chernobyl papillary thyroid cancer. AB - PURPOSE: Following the nuclear accidents in Chernobyl and later in Fukushima, the nuclear community has been faced with important issues concerning how to search for and diagnose biological consequences of low-dose internal radiation contamination. Although after the Chernobyl accident an increase in childhood papillary thyroid cancer (PTC) was observed, it is still not clear whether the molecular biology of PTCs associated with low-dose radiation exposure differs from that of sporadic PTC. METHODS: We investigated tissue samples from 65 children/young adults with PTC using DNA microarray (Affymetrix, Human Genome U133 2.0 Plus) with the aim of identifying molecular differences between radiation-induced (exposed to Chernobyl radiation, ECR) and sporadic PTC. All participants were resident in the same region so that confounding factors related to genetics or environment were minimized. RESULTS: There were small but significant differences in the gene expression profiles between ECR and non-ECR PTC (global test, p < 0.01), with 300 differently expressed probe sets (p < 0.001) corresponding to 239 genes. Multifactorial analysis of variance showed that besides radiation exposure history, the BRAF mutation exhibited independent effects on the PTC expression profile; the histological subset and patient age at diagnosis had negligible effects. Ten genes (PPME1, HDAC11, SOCS7, CIC, THRA, ERBB2, PPP1R9A, HDGF, RAD51AP1, and CDK1) from the 19 investigated with quantitative RT-PCR were confirmed as being associated with radiation exposure in an independent, validation set of samples. CONCLUSION: Significant, but subtle, differences in gene expression in the post-Chernobyl PTC are associated with previous low-dose radiation exposure. PMID- 26810420 TI - PHOTO QUIZ. Cerebropulmonary Nodules in a Renal Allograft Recipient. PMID- 26810423 TI - Bright tongue sign in Pompe disease. PMID- 26810422 TI - Breast cancer survivors' perspectives of critical lymphedema self-care support needs. AB - PURPOSE: To solicit breast cancer survivors' perspectives on the variety of issues they face related to lymphedema self-care and identify support needs perceived as critical for managing their chronic medical condition. METHODS: Twenty-one breast cancer survivors with lymphedema participated in audio-recorded focus groups about barriers and facilitators of self-care. Transcripts were analyzed using ATLAS.ti software by two coders. Triangulation of findings provided for refinement and category confirmation. RESULTS: Themes identified included lack of social support, lack of resources for self-care activities, and self-advocacy by default. Lack of social support subthemes were feeling misunderstood, minimization of needs, and feeling criticized. Lack of resources for self-care activities subthemes were lack of both tangible self-care support and self-care supplies. Self-advocacy by default subthemes were the need to proactively manage lymphedema complications, the need to educate health-care workers, and feeling marginalized by the health-care system. CONCLUSIONS: Lack of support and the failure of others to recognize lymphedema as a chronic condition set this patient population apart from other patients with chronic diseases and decreases the amount of help needed to manage the condition. PMID- 26810424 TI - Coexistence of ocular neuromyotonia and hemifacial spasm. PMID- 26810425 TI - Structure of neuroscience clerkships in medical schools and matching in neuromedicine. PMID- 26810426 TI - Structure of neuroscience clerkships in medical schools and matching in neuromedicine. PMID- 26810427 TI - Mystery Case: Rim enhancement in cerebral aneurysm: An atypical feature. PMID- 26810428 TI - Teaching NeuroImages: Longitudinally extensive transverse myelitis in MELAS. PMID- 26810429 TI - Teaching NeuroImages: Extensive vasogenic edema in Bickerstaff brainstem encephalitis. PMID- 26810430 TI - Voice of young neurologists around the world. PMID- 26810431 TI - Diagnosing idiopathic intracranial hypertension: What patients should know. PMID- 26810432 TI - Tuning a High Transmission Ion Guide to Prevent Gas-Phase Proton Exchange During H/D Exchange MS Analysis. AB - Hydrogen/deuterium exchange (HDX) mass spectrometry (MS) for protein structural analysis has been adopted for many purposes, including biopharmaceutical development. One of the benefits of examining amide proton exchange by mass spectrometry is that it can readily resolve different exchange regimes, as evidenced by either binomial or bimodal isotope patterns. By careful analysis of the isotope pattern during exchange, more insight can be obtained on protein behavior in solution. However, one must be sure that any observed bimodal isotope patterns are not artifacts of analysis and are reflective of the true behavior in solution. Sample carryover and certain stationary phases are known as potential sources of bimodal artifacts. Here, we describe an additional undocumented source of deuterium loss resulting in artificial bimodal patterns for certain highly charged peptides. We demonstrate that this phenomenon is predominantly due to gas phase proton exchange between peptides and bulk solvent within the initial stages of high-transmission conjoined ion guides. Minor adjustments of the ion guide settings, as reported here, eliminate the phenomenon without sacrificing signal intensity. Such gas-phase deuterium loss should be appreciated for all HDX-MS studies using such ion optics, even for routine studies not focused on interpreting bimodal spectra. Graphical Abstract ?. PMID- 26810433 TI - Theoretical Study of Dual-Direction Dipolar Excitation of Ions in Linear Ion Traps. AB - The ion enhanced activation and collision-induced dissociation (CID) by simultaneous dipolar excitation of ions in the two radial directions of linear ion trap (LIT) have been recently developed and tested by experiment. In this work, its detailed properties were further studied by theoretical simulation. The effects of some experimental parameters such as the buffer gas pressure, the dipolar excitation signal phases, power amplitudes, and frequencies on the ion trajectory and energy were carefully investigated. The results show that the ion activation energy can be significantly increased by dual-direction excitation using two identical dipolar excitation signals because of the addition of an excitation dimension and the fact that the ion motion radius related to ion kinetic energy can be greater than the field radius. The effects of higher-order field components, such as dodecapole field on the performance of this method are also revealed. They mainly cause ion motion frequency shift as ion motion amplitude increases. Because of the frequency shift, there are different optimized excitation frequencies in different LITs. At the optimized frequency, ion average energy is improved significantly with relatively few ions lost. The results show that this method can be used in different kinds of LITs such as LIT with 4-fold symmetric stretch, linear quadrupole ion trap, and standard hyperbolic LIT, which can significantly increase the ion activation energy and CID efficiency, compared with the conventional method. PMID- 26810435 TI - "What is Life Like in the Twilight Years?" A Letter About the Scant Amount of Literature on the Elderly with Autism Spectrum Disorders. AB - The purpose of this letter is to show the lack of published literature on elderly adults with Autism Spectrum Disorders. PMID- 26810434 TI - The Longitudinal Effects of Network Characteristics on the Mental Health of Mothers of Children with ASD: The Mediating Role of Parent Cognitions. AB - Employing a cohort sequential design, the effects of network characteristics on maternal cognitions (perceived social support and parenting self-efficacy) and mental health (depression and well-being) were assessed over 7 years when children with ASD of mothers in the study were age 7-14. Findings indicated that network size, network emotional support, and network instrumental support were positively related to perceived support, while network availability and emotional support were positively linked to self-efficacy. In addition, network support exerted direct and indirect effects on maternal depression and well-being, with cognitive resources mediating the social network-mental health relationship. Finally, consistent with the support-efficacy model, parenting efficacy partially mediated the effects of perceived support on maternal mental health outcomes. Study findings and implications are discussed. PMID- 26810436 TI - Factors Influencing the Research Participation of Adults with Autism Spectrum Disorders. AB - Recruiting adults with autism spectrum disorders (ASD) into research poses particular difficulties; longitudinal studies face additional challenges. This paper reports on a mixed methods study to identify factors influencing the participation in longitudinal autism research of adults with ASD, including those with an intellectual disability, and their carers. Common and differentiating factors influencing the research participation of participants are identified and discussed. Factors influencing participation were found to differ both between and within participant categories. We propose a dichotomy whereby factors influencing research participation can be classified as those arising from a participant's values, which act as either a motivator or a deterrent; and those based on convenience, which act as either an enabler or inhibitor. These findings are applicable to research studies that seek to recruit adults with ASD as participants. PMID- 26810438 TI - Social cognition and metacognition in obsessive-compulsive disorder: an explorative pilot study. AB - Obsessive-compulsive disorder (OCD) is a severe psychiatric condition that is, among other features, characterized by marked impairment in social functioning. Although theoretically plausible with regard to neurobiological underpinnings of OCD, there is little research about possible impairments in social cognitive and meta-cognitive abilities and their connections with social functioning in patients with OCD. Accordingly, we sought to examine social cognitive skills and metacognition in OCD. Twenty OCD patients and age-, sex-, and education-matched 20 healthy controls were assessed using neurocognitive and diverse social cognitive skills including the Ekman 60 Faces test, the Hinting Task, the faux pas test, and a proverb test. In addition, the Metacognition Questionnaire-30 was administered to both the OCD and the control groups. Social functioning was measured using the Personal and Social Performance Scale. Symptom severity in patients was determined by the Yale-Brown Obsessive-Compulsive Scale and the Maudsley Obsessive-Compulsive Inventory. No group differences emerged in basic social cognitive abilities. In contrast, compared to controls, OCD patients scored higher on all MCQ dimensions, particularly negative beliefs about worry, uncontrollability, and danger; beliefs about need to control thoughts; and cognitive self-consciousness. There were no significant correlations between social or metacognitive parameters and OCD symptom severity. However, in the patient group, depression and metacognition predicted social functioning. OCD patients show normal basal social cognitive abilities, but dysfunctional metacognitive profiles, which may contribute to their psychosocial impairment. PMID- 26810439 TI - African American Transgender Women's Individual, Family, and Organizational Relationships: Implications for Nurses. AB - Guided by the relational cultural theory, we conducted a qualitative study to examine the relationship experiences of African American transgender women living in North Carolina. A convenience sample of 15 transgender women participated in the study. Semi-structured interviews, guided by an investigator-developed interview guide, were used to explore the personal experiences of transgender women on individual, family, and organizational levels. The findings provide a scheme for understanding the process through which transgender women's relationships hinder or enhance their ability to connect with individuals, family, and organizations. Nurses can use these findings to better understand the connectedness that occurs or does not occur in transgender women's relationships and provide culturally competent care to empower them to become resilient. PMID- 26810440 TI - Using the Short-Form Cigarette Dependence Questionnaire in a Busy Clinical Practice. AB - The aim of this study was to refine the long version of the Cigarette Dependence Questionnaire (CDQ-29) that includes 29-items by removing some redundant questions, and then examining the predictive utility of the resulting scale in terms of its ability to explain saliva cotinine level, and testing the measurement structure of the remaining items. Across three diverse independent samples of smokers, we developed a one-factor CDQ-12 that showed good internal consistency and concurrent validity that was comparable with the CDQ-29. The proposed model was a good fit for the data. The reliability coefficient was .92, and the score of the 12-item CDQ had a moderate correlation with the total score of cigarette withdrawal ( r = .63, p < .01). The CDQ-12 is a reliable and valid Chinese-language instrument to assess cigarette dependence, which can be used to guide nursing interventions that support culturally and socially appropriate smoking cessation programs. PMID- 26810437 TI - Partners in Crime: The Role of CMV in Immune Dysregulation and Clinical Outcome During HIV Infection. AB - In the current era of combination antiretroviral therapy (ART), human immunodeficiency virus (HIV)-infected individuals are living longer and healthier lives. Nevertheless, HIV-infected persons are at greater risk for age-related disorders, which have been linked to residual immune dysfunction and inflammation. HIV-infected individuals are almost universally co-infected with cytomegalovirus (CMV) and both viruses are associated with inflammation-related morbidities. Therefore, a detailed investigation of the relationship between CMV and aging-related morbidities emerging during chronic HIV infection is warranted. Here, we review the literature on how CMV co-infection affects HIV infection and host immunity and we discuss the gaps in our knowledge that need elucidation. PMID- 26810441 TI - Extranasal symptoms of allergic rhinitis are difficult to treat and affect quality of life. AB - BACKGROUND: Total nasal symptom score is widely used to evaluate the severity of allergic rhinitis, but the clinical significance of extranasal symptoms is largely unknown. We wished to analyze the presenting symptoms in allergic rhinitis, as well as their relationship with quality of life (QoL) and therapeutic outcomes. METHODS: Presenting symptoms and QoL were assessed using the OptumTM SF-12v2((r)) Health Survey in 260 patients with allergic rhinitis. Clinical response at 3 months after treatment was measured. RESULTS: Ten most common symptoms presenting with at least moderate severity in allergic rhinitis were: blocked nose (82.7%), rhinorrhea (75.0%), sneeze (70.9%), itchy nose (68.5%), fatigue (63.6%), mouth breathing (61.1%), daytime somnolence (52.7%), postnasal drip (49.1%), itchy eyes (47.3%), and dry mouth (46.3%). Severity of sneeze was correlated with physical component summary (PCS) whereas postnasal drip and daytime somnolence were correlated with mental component summary (MCS). Severity of dry mouth was correlated with PCS and MCS. The symptoms with the highest severity scores after treatment were blocked nose, postnasal drip, fatigue, and dry mouth, respectively. CONCLUSIONS: Extranasal symptom scores correlated well with physical health and mental health in allergic rhinitis patients. Assessment of extranasal symptoms should be included to evaluate disease severity and assess therapeutic outcomes. Clinical trial NCT02000648, http://www.clinicaltrials.gov. PMID- 26810444 TI - Burn unit care of Stevens Johnson syndrome/toxic epidermal necrolysis: A survey. AB - Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a systemic disease that can be associated with debilitating acute and chronic complications across multiple organ systems. As patients with acute SJS/TEN are often treated in a burn intensive care unit (BICU), we surveyed burn centers across the United States to determine their approach to the care of these patients. The goal of our study was to identify best practices and possible variations in the care of patients with acute SJS/TEN. We demonstrate that the method of diagnosis, use of systemic therapies, and involvement of subspecialists varied significantly between burn centers. Beyond supportive care provided to every patient, our data highlights a lack of standardization in the acute care of patients with SJS/TEN. A comprehensive guideline for the care of patients with acute SJS/TEN is indicated. PMID- 26810442 TI - Effects on Weight, Blood Lipids, Serum Fatty Acid Profile and Coagulation by an Energy-Dense Formula to Older Care Residents: A Randomized Controlled Crossover Trial. AB - OBJECTIVES: Dietary intake in frail old adults is often lower than estimated needs. The aim of this study was to evaluate the effects of an energy-dense oral supplement on nutritional status, food intake, and physical function in residents living in care residential homes. DESIGN: Randomized controlled intervention trial with a crossover design. SETTING: Five care residential homes in the southern Stockholm area. PARTICIPANTS: Older people living at care residential homes: age 65 or older, malnourished or at risk of malnutrition according to Mini Nutritional Assessment-Short Form (MNA-SF). INTERVENTION: Energy-dense formula (oleic and linoleic acid emulsion enriched with protein and micronutrients) (Calogen Extra, Nutricia) 30 mL distributed 3 times daily for 6 weeks. MEASUREMENTS: Body weight, 3-day food and fluid record, appetite rating, and physical function (ie, Short Physical Performance Battery, grip strength, and peak expiratory flow). Biochemical indicators of nutritional status, blood lipids, and serum phospholipid fatty acid (FA) profile. RESULTS: Twenty-eight participants completed the 2 phases of the crossover study; group A (n = 14, 87 +/- 6 years, 50% women) and group B (n = 14, 82 +/- 8 years, 71% women). The intervention periods combined resulted in significantly (P < .05) increased energy intake (238 +/- 544 kcal), weight gain (1.4 +/- 3.7 kg), improved appetite, relative reduction of saturated FA and increase in polyunsaturated FA, increased apoliporotein A, and reduced serum fibrinogen (-0.9 +/- 1.5 g/L). CONCLUSION: Distribution of an oleic and linoleic acid based fat emulsion enriched with protein and micronutrients (Calogen Extra) 3 times daily to old people in care residential homes improved nutritional status, had positive effects on fatty acid profile and blood lipids, and a potential antithrombotic effect. CLINICALTRIALS. GOV IDENTIFIER: NCT01259999. PMID- 26810445 TI - Microvascular blood flow in scalds in children and its relation to duration of wound healing: A study using laser speckle contrast imaging. AB - BACKGROUND: Microvascular perfusion changes in scalds in children during the first weeks after injury is related to the outcome of healing, and measurements of perfusion, based on laser Doppler imaging, have been used successfully to predict the need for excision and grafting. However, the day-to-day changes in perfusion during the first weeks after injury have not to our knowledge been studied in detail. The aim of this study, based on a conservative treatment model where excision and grafting decisions were delayed to day 14 after injury, was to measure changes in perfusion in scalds using laser speckle contrast imaging (LSCI) during the first three weeks after injury. METHODS: We measured perfusion with LSCI in 34 patients at regular intervals between 6h after injury until complete reepithelialization or surgery. Duration of healing was defined as the time to complete reepithelialization. RESULTS: Less perfusion, between 6 and 96h after injury, was associated with longer duration of healing with the strongest association occurring between 72 and 96h. Burns that healed within 14 days had relatively high initial perfusion, followed by a peak and subsequent slow decrease. Both the maximum perfusion and the time-to-peak were dependent on the severity of the burn. Burns that needed excision and grafting had less initial perfusion and a gradual reduction over time. CONCLUSION: The perfusion in scalds in children shows characteristic patterns during the first weeks after injury depending on the duration of wound healing, the greatest difference between wounds of different severity being on the 4th day. Perfusion should therefore preferably be measured on the fourth day if it is to be used in the assessment of burn depth. PMID- 26810446 TI - The financial impact of head and neck cancer caregiving: a qualitative study. AB - BACKGROUND: There is a lack of research on the financial impacts that head and neck cancer has on caregivers. OBJECTIVE: To explore the overall financial impact of head and neck cancer on caregivers; to describe the factors that mitigate this impact. METHODS: Interviews with 31 caregivers (mean time caring: 5.7 years). RESULTS: Head and neck cancer had a considerable financial impact on caregivers. It resulted in out of pocket costs and caregivers and/or their relative/friend with cancer often became under- or un-employed. Caregivers with large debts or ongoing expenses appeared to be particularly vulnerable to cancer-related financial pressures. Finance related psychological stress was prevalent, although some caregivers hid their psychological difficulties from other people. Factors which help caregivers to mitigate financial distress included having private health insurance and being able to access to medical and/or social welfare benefits. CONCLUSIONS: Head and neck cancer can cause caregivers substantial financial and psychological distress. Distress may be mitigated by providing caregivers and their households with access to welfare benefits. IMPLICATIONS FOR PRACTICE: Health professionals should be aware that head and neck cancer can have short and long-term financial consequences for caregivers and their families. Health professionals should refer patients and their caregivers to medical social workers who can help them with their financial issues. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26810447 TI - Potential Effects of Interleukins on the Pathogenesis of Systemic Onset Juvenile Idiopathic Arthritis. AB - BACKGROUND: To analyze the correlation of cytokines with clinical inflammatory indexes in systemic onset juvenile idiopathic arthritis (SOJIA). METHODS: A total of 30 active SOJIAs, 30 remission SOJIAs, and 20 normal controls were enrolled. The clinical inflammatory indexes such as tender joints counts, swelling joints counts, C-reactive protein, erythrocyte sedimentation rate, visual analogue scale (VAS), and disease activity score 28 (DAS28) were detected. The serum cytokines interleukin (IL)-17, IL-6, IL-21, interferon (IFN)-gamma, and IL-4 levels were determined with enzyme-linked immunosorbent assay method. The correlation coefficients between these cytokines and two clinical indexes (VAS and DAS28) in the active SOJIA group were calculated with the Spearman's method. RESULTS: The serum IL-17 and IL-6 levels in active SOJIA group were significantly increased compared with those in the remission SOJIA group and control group (p < 0.05), and the serum IL-21, IFN-gamma, and IL-4 levels showed no obvious difference. In the active SOJIA group, the Spearman coefficients between IL-17 and DAS28, IL-17 and IL-6, IL-6 and DAS28, and between IL-17 and VAS were 0.686 (p = 0.000), 0.833 (p = 0.000), 0.633 (p = 0.000), and 0.524 (p = 0.003), respectively. There was no correlation between cytokines of IL-21, IFN-gamma, and IL-4 and the clinical indexes of DAS28 and VAS. Furthermore, in the other two groups, none of the five cytokines exhibited an association with DAS28 or VAS. CONCLUSION: IL-6 and IL-17 were significantly correlated with DAS28 and VAS, and they might be considered as therapeutic targets for the treatment of SOJIA. PMID- 26810448 TI - Jasmonate complements the function of Arabidopsis lipoxygenase3 in salinity stress response. AB - The functions of jasmonic acid (JA) in various stress responses have been uncovered in details, but its role in salt tolerance remains unclear. Here, we characterize the function of Arabidopsis lipoxygenase3 (LOX3), an enzyme involved in JA synthesis, in salt stress response. The transcriptional analysis indicated that LOX3 was dramatically induced under salt treatment. Compared with wild type, the lox3 mutant exhibited hypersensitivity to salt stress in germination and different developmental stages. Interestingly, methyl jasmonate (MeJA) rescued the salt sensitivity phenotypes of the lox3 mutant, suggesting the impairment of salinity response in the mutant may be mediated by JA. Furthermore, the lateral root number of the lox3 mutant was similar with that in wild type under normal condition, but less than that in wild type during salt treatment, and this lateral root sensitivity phenotype was also complemented by exogenous MeJA. In addition, the measurement of oxylipins in the lox3 mutant and the analysis on germination of the JA receptor coi1 mutant under salt stress supported that JA may regulate the early response to salinity. In conclusion, we characterized the novel function of LOX3 in salinity stress response, and found that the salt hypersensitivity of the lox3 mutant can be complemented by MeJA, providing new evidence for the association between JA and salt tolerance. PMID- 26810449 TI - The molybdenum cofactor biosynthesis complex interacts with actin filaments via molybdenum insertase Cnx1 as anchor protein in Arabidopsis thaliana. AB - The pterin based molybdenum cofactor (Moco) plays an essential role in almost all organisms. Its biosynthesis is catalysed by six enzymes in a conserved four step reaction pathway. The last three steps are located in the cytoplasm, where a multimeric protein complex is formed to protect the intermediates from degradation. Bimolecular fluorescence complementation was used to test for cytoskeleton association of the Moco biosynthesis enzymes with actin filaments and microtubules using known cytoskeleton associated proteins, thus permitting non-invasive in vivo studies. Coding sequences of binding proteins were cloned via the GATEWAY system. No Moco biosynthesis enzyme showed any interaction with microtubules. However, alone the two domain protein Cnx1 exhibited interaction with actin filaments mediated by both domains with the Cnx1G domain displaying a stronger interaction. Cnx6 showed actin association only if unlabelled Cnx1 was co-expressed in comparable amounts. So Cnx1 is likely to be the anchor protein for the whole biosynthesis complex on actin filaments. A stabilization of the whole Moco biosynthesis complex on the cytoskeleton might be crucial. In addition a micro-compartmentation might either allow a localisation near the mitochondrial ATM3 exporter providing the first Moco intermediate or near one of the three molybdate transporters enabling efficient molybdate incorporation. PMID- 26810450 TI - Functional and transcriptional characterization of a barley mutant with impaired photosynthesis. AB - Chemical mutagenesis induces variations that may assist in the identification of targets for adaptation to growth under atmospheric CO2 enrichment. The aim of this work was to characterize the limitations causing reduced photosynthetic capacity in G132 mutagenized barley (Hordeum vulgare L. cv. Graphic) grown in a glasshouse. Compared to the wild type (WT) G132 showed increased transcript levels for the PSII light harvesting complex, but lower levels of chlorophyll, transcripts for protochlorophyllide oxidoreductase A and psbQ, and PSII quantum efficiency in young leaves. Rubisco limitation had an overriding influence on G132 photosynthesis, and was due to strong and selective decreases in Rubisco protein and activity. These reductions were accompanied by enhanced Rubisco transcripts, but increased levels of a Rubisco degradation product. G132 showed lower levels of carbohydrates, amino acids and corresponding transcripts, and proteins, but not of nitrate. Many of the measured parameters recovered in the mutant as development progressed, or decreased less than in the WT, indicating that senescence was delayed. G132 had a longer growth period than the WT and similar final plant dry matter. The reduced resource investment in Rubisco of G132 may prove useful for studies on barley adaptation to elevated CO2 and climate change. PMID- 26810451 TI - Specific roles of tocopherols and tocotrienols in seed longevity and germination tolerance to abiotic stress in transgenic rice. AB - Tocopherols and tocotrienols are lipophilic antioxidants that are abundant in plant seeds. Although their roles have been extensively studied, our understanding of their functions in rice seeds is still limited. In this study, on the basis of available RNAi rice plants constitutively silenced for homogentisate phytyltransferase (HPT) and tocopherol cyclase (TC), we developed transgenic plants that silenced homogentisate geranylgeranyl transferase (HGGT). All the RNAi plants showed significantly reduced germination percentages and a higher proportion of abnormal seedlings than the control plants, with HGGT transgenics showing the most severe phenotype. The accelerated aging phenotype corresponded well with the amount of H2O2 accumulated in the embryo, glucose level, and ion leakage, but not with the amount of O(2-) accumulated in the embryo and lipid hydroperoxides levels in these genotypes. Under abiotic stress conditions, HPT and TC transgenics showed lower germination percentage and seedling growth than HGGT transgenics, while HGGT transgenics showed almost the same status as the wild type. Therefore, we proposed that tocopherols in the germ may protect the embryo from reactive oxygen species under both accelerated aging and stress conditions, whereas tocotrienols in the pericarp may exclusively help in reducing the metabolic activity of the seed during accelerated aging. PMID- 26810452 TI - Molecular candidates for early-stage flower-to-fruit transition in stenospermocarpic table grape (Vitis vinifera L.) inflorescences ascribed by differential transcriptome and metabolome profiles. AB - Flower-to-fruit transition depends of nutrient availability and regulation at the molecular level by sugar and hormone signalling crosstalk. However, in most species, the identities of fruit initiation regulators and their targets are largely unknown. To ascertain the main pathways involved in stenospermocarpic table grape fruit set, comprehensive transcriptional and metabolomic analyses were conducted specifically targeting the early phase of this developmental stage in 'Thompson Seedless'. The high-throughput analyses performed disclosed the involvement of 496 differentially expressed genes and 28 differently accumulated metabolites in the sampled inflorescences. Our data show broad transcriptome reprogramming of molecule transporters, globally down-regulating gene expression, and suggest that regulation of sugar- and hormone-mediated pathways determines the downstream activation of berry development. The most affected gene was the SWEET14 sugar transporter. Hormone-related transcription changes were observed associated with increased indole-3-acetic acid, stimulation of ethylene and gibberellin metabolisms and cytokinin degradation, and regulation of MADS-box and AP2-like ethylene-responsive transcription factor expression. Secondary metabolism, the most representative biological process at transcriptome level, was predominantly repressed. The results add to the knowledge of molecular events occurring in grapevine inflorescence fruit set and provide a list of candidates, paving the way for genetic manipulation aimed at model research and plant breeding. PMID- 26810453 TI - Tomato response traits to pathogenic Pseudomonas species: Does nitrogen limitation matter? AB - Induced chemical defence is a cost-efficient protective strategy, whereby plants induce the biosynthesis of defence-related compounds only in the case of pest attack. Plant responses that are pathogen specific lower the cost of defence, compared to constitutive defence. As nitrogen availability (N) in the root zone is one of the levers mediating the concentration of defence-related compounds in plants, we investigated its influence on response traits of tomato to two pathogenic bacteria, growing plants hydroponically at low or high N supply. Using two sets of plants for each level of N supply, we inoculated one leaf of one set of plants with Pseudomonas syringae, and inoculated the stem of other set of plants with Pseudomonas corrugata. Tomato response traits (growth, metabolites) were investigated one and twelve days after inoculation. In infected areas, P. syringae decreased carbohydrate concentrations whereas they were increased by P. corrugata. P. syringae mediated a redistribution of carbon within the phenylpropanoid pathway, regardless of N supply: phenolamides, especially caffeoylputrescine, were stimulated, impairing defence-related compounds such as chlorogenic acid. Inoculation of P. syringae produced strong and sustainable systemic responses. By contrast, inoculation of P. corrugata induced local and transient responses. The effects of pathogens on plant growth and leaf gas exchanges appeared to be independant of N supply. This work shows that the same genus of plant pathogens with different infection strategies can mediate contrasted plant responses. PMID- 26810454 TI - Beneficial effects of an Andrographis paniculata extract and andrographolide on cognitive functions in streptozotocin-induced diabetic rats. AB - Context Andrographolide containing Andrographis paniculata (Burm. F.) Wall. Ex Nees (Acanthaceae) extracts is often used for treatments of diabetes and other inflammatory disorders commonly accompanying cognitive and other psychiatric disorders. Objective To compare the efficacies of a standardised A. paniculata extract (AP) and pure andrographolide on cognitive functions, oxidative stress and cholinergic function in diabetic rats. Materials and methods Streptozotocin induced diabetic Charles Foster albino rats treated orally with a hydro methanolic A. paniculata leaf extract (50, 100 and 200 mg/kg/day), or with pure andrographolide (15, 30 and 60 mg/kg/day) for 10 consecutive days, were subjected to Morris water maze test. After the test, acetylcholinesterase, superoxide dismutase (SOD), and catalase (CAT) activities and lipid peroxidation (LPO) in brain tissues were assessed. Results Acetylcholinesterase activity in pre-frontal cortex and hippocampus of diabetic rats was 2.1 and 2.6 times higher compared to nondiabetic rats. LPO was 1.6 times higher and decreased SOD (56.3%) and CAT (44.9%) activities in pre-frontal cortex of diabetic rats compared to nondiabetic rats. AP or andrographolide treatments dose dependently attenuated cognitive deficits, reduced acetylcholinesterase activity, oxidative stress, improved diabetic hyperglycemia and insulin deficiency. All observed effects of AP were quantitatively almost equal to those expected from its analytically quantified andrographolide content. Discussion and conclusion Reported observations are the very first ones suggesting beneficial effects of andrographolide against diabetes associated cognitive deficits, increased acetylcholinesterase activity and deteriorated antioxidative status. Efforts to exploit A. paniculata extracts enriched in andrographolide as preventive measures against such disorders can be warranted. PMID- 26810457 TI - Real-Time Monitoring of G-Quadruplex Formation during Transcription. AB - Cotranscriptional folding of an RNA transcript enables formation of metastable RNA structures. Thermodynamic and kinetic properties of RNA G-quadruplex formation have previously been investigated using purified guanine-rich oligonucleotides. Here, we describe a method for analysis of cotranscriptional dynamics of the G-quadruplex formation based on real-time monitoring of the fluorescence of G-quadruplex ligands. For RNA sequences with the potential to form mutually exclusive hairpin or G-quadruplex structures, the efficiency of G quadruplex formation during transcription depended on position of the hairpin forming sequence. The real-time monitoring enabled evaluation of environmental effects on RNA dynamics, as we demonstrated facilitation of post-transcriptional G-quadruplex formation under molecular crowding conditions. The strategy demonstrated here provides folding insights into the G-quadruplex during transcription that should be involved in gene regulation. PMID- 26810455 TI - The long-term and extensive efficacy of low dose thalidomide in a case of an untransfusable patient with Non-Transfusion-Dependent Thalassemia. AB - Patients with Non-Transfusion-Dependent Thalassemia may require regular transfusion therapy. However, these patients are at risk of developing irregular antibodies, making them untransfusable. Second line treatment usually includes hydroxyurea, which however is not effective in all patients. Other treatment options include thalidomide, which has been reported to be safe and effective in selected patients. We report the case of a patient who experienced improvement of hemoglobin levels and of a part of NTDT related complications, following 36months of continuous therapy with low doses of thalidomide. PMID- 26810458 TI - Dry skin in nursing care receivers: A multi-centre cross-sectional prevalence study in hospitals and nursing homes. AB - BACKGROUND: Maintaining and improving skin health of patients and long-term care receivers is a widely agreed upon goal in health and nursing care. Care dependent and aged persons have a high predisposition to develop dry skin conditions. OBJECTIVES: The aim of this study was to estimate the prevalence and severity of skin dryness in hospitals and nursing homes and to identify person- and health related variables associated with this skin condition. DESIGN: The study was part of a bigger annual multicentre descriptive cross-sectional prevalence study of health problems. SETTINGS/PARTICIPANTS: Fourteen nursing homes and six hospitals in Germany participated in this study in 2014. A total of 1710 subjects (n=1091 long-term care residents and n=619 in-patients) were included. METHODS: Skin assessments were conducted and skin dryness was measured using the Overall Dry Skin Score. Mobility was measured using the respective item of the Care Dependency Scale. Demographic, functional and physiological parameters were compared between subjects with and without dry skin. A logistic regression model predicting skin dryness was created. RESULTS: The prevalence of skin dryness was 48.8% (95% CI 46.5-51.2). Nursing home residents were most often affected (52.6%; 95% CI 49.6-55.6) compared to in-patients (42.2%; 95% CI 38.3-46.1). The skin of feet and legs were most often affected by skin dryness (42.9%) compared to other skin areas. Being older (OR 1.01; 95% CI 1.01-1.02), having pruritus (OR 14.21; 95% CI 8.00-22.95), oncological (OR 1.95; 95% CI 1.30-2.91), musculoskeletal diseases (OR 1.31; 95% CI 1.04-1.64), being skin care independent (OR 0.48; 95% CI 0.32-0.70) were the strongest covariates for the presence of dry skin in the multivariate model. CONCLUSIONS: Based on a large sample results indicate that approximately every second nursing home resident and hospital in-patient are affected by dry skin. Severe forms occur more often in hospital in-patients compared to nursing home residents. Skin care interventions to tackle dry skin are recommended particularly for hospital patients and nursing home residents who are affected by pruritus or oncological diseases, who are in need of washing/bathing assistance, and who have musculoskeletal diseases. PMID- 26810462 TI - Lewy- and Alzheimer-type pathologies in midbrain and cerebellum across the Lewy body disorders spectrum. AB - AIMS: Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are pathologically characterized by intraneuronal alpha-synuclein aggregates and thus labelled as Lewy body disorders (LBD). Conjoint cortical alpha-synuclein, tau and amyloid-beta (Abeta), and striatal Abeta aggregates, have been related to dementia in LBD. Interpretation of current and emerging in vivo molecular imaging of these pathologies will need of precise knowledge of their topographic distribution. We aimed to assess these pathologies further down the encephalon across the LBD-spectrum. METHODS: Semiquantitative rating of alpha-synuclein, Abeta and hyperphosphorylated tau aggregates in midbrain (and cerebellum in the case of Abeta as it represents the last beta-amyloidosis stage) sections from cases representative of the LBD-spectrum (PD non-dementia, PD-dementia, DLB; n = 10 each) compared to controls (n = 10) and Alzheimer's disease (AD; n = 10). RESULTS: alpha-synuclein midbrain scores rose from controls to AD and then LBD irrespective of dementia. Abeta and tau were more prominent in the tectum/tegmentum, increasing from controls to LBD (mostly in dementia cases in the case of Abeta), and then peaking in AD. By contrast, cerebellar Abeta scores were marginal across the LBD-spectrum, as opposed to AD, only showing a trend towards greater involvement in LBD cases with dementia. CONCLUSIONS: Frequency and severity of Abeta and tau pathologies in the midbrain across the LBD-spectrum were midway between controls and AD, with Abeta in the tectum/tegmentum being associated with dementia. These findings might have potential implications in the eventual interpretation of regional uptake of in vivo molecular imaging of these pathologies. PMID- 26810463 TI - Polymer nanoparticle delivery of dichloroacetate and DACH-Pt to enhance antitumor efficacy and lower systemic toxicity. AB - Platinum agents can cause DNA damage and thus induce apoptosis of cancer cells, which has made them the backbone of cancer chemotherapy regimens. However, most cancers will develop drug resistance over the course of treatment. Meanwhile, most tumors meet energy needs largely by aerobic glycolysis (glycolysis in the presence of oxygen, called the Warburg effect), which is related to their resistance to apoptosis. Therefore, we have used a biodegradable polymer carrier to conjugate with DACH-Pt and dichloroacetate, a PDK inhibitor that can reverse the Warburg effect and derepress the resistance to apoptosis, thus sensitizing cancer cells to platinum. The as-prepared polymer-drug conjugates can be assembled into nanoparticles for effective delivery and better synergism. In vitro and in vivo studies revealed that the combination of polymer-DCA and polymer-DACH-Pt are much better than the free drugs administered simultaneously, in terms of both safety and antitumor efficacy. PMID- 26810464 TI - Correction to Appalachian Mountaintop Mining Particulate Matter Induces Neoplastic Transformation of Human Bronchial Epithelial Cells and Promotes Tumor Formation. PMID- 26810466 TI - Synthesis of tetra-substituted 5-trifluoromethylpyrazoles via sequential halogenation/palladium-catalyzed C-C and C-N cross-coupling. AB - A mild and efficient protocol for the assembly of tetra-substituted 5 trifluoromethylpyrazoles is presented, involving halogenation at the 4-position of readily prepared tri-substituted 5-trifluoromethylpyrazoles to give 4-halo-1 phenyl-5-trifluoromethyl pyrazoles, and subsequent palladium-catalyzed Negishi or Buchwald-Hartwig cross-couplings to install carbon or nitrogen-based 4 substituents. Key to the success of these challenging cross-couplings is the use of XPhos and JosiPhos CyPF-tBu ligands, respectively. PMID- 26810467 TI - Early deep brain stimulation in patients with myoclonus-dystonia syndrome. AB - Myoclonus-dystonia (MD) is a rare movement disorder which is disabling and frequently refractory to medical treatment. Deep brain stimulation (DBS) of the globus pallidus interna (GPi) has been used to treat some patients. Although there is significant motor improvement with DBS, the impact on disability and on quality of life has been infrequently reported. Also, the benefit of the procedure is not established in patients without epsilon-sarcoglycan gene (SGCE) mutations. We present two patients with severe MD treated with GPi-DBS, one of the patients without a SGCE mutation. Motor improvements (rest/action/total subscores of the Unified Myoclonus Rating Scale and movement subscore of the Burke-Fahn-Marsden Dystonia Rating Scale [BFMRS]) and disability (BFMRS disability subscore) were carefully evaluated preoperatively and at 6 and 12months after surgery. Quality of life (addressed using the Portuguese version of the Medical Outcomes Study 36-item Short-Form General Health Survey, version 2.0 [SF-36v2]) was tested preoperatively and 12months after DBS. At 12-month follow-up, myoclonus improved 78.6% in Patient 1 and 80.7% in Patient 2, while dystonia improved 37% and 86.7%, respectively. Improvements in disability ranged from 71.4% to 75%. With regard to quality of life, all parameters addressed by the SF-36v2 improved or stabilized in both patients. No major adverse effects were noticed. Improvements in motor symptoms are consistent with reports in the literature and were obtained regardless of the identification of a SGCE gene mutation. There were also significant benefits on disability and quality of life. DBS should be considered for MD. PMID- 26810469 TI - Higher expression of monocyte chemoattractant protein 1 and its receptor in brain tissue of intractable epilepsy patients. AB - We aimed to explore the pathogenesis of monocyte chemoattractant protein-1 (MCP1) and CC chemokine receptor 2 (CCR2) in brain tissue of patients with intractable epilepsy (IE). Hippocampi or temporal lobe tissues were obtained from 40 patients with IE and five patients without IE who had undergone surgical decompression and debridement. The levels of MCP1 and CCR2 were evaluated using immunohistochemistry. Pearson correlation analysis was employed to evaluate the correlation between levels of MCP1 and CCR2 in IE with or without hippocampal sclerosis (HS) and the disease duration, along with age. Higher levels of MCP1 (11.68+/-4.68% versus 1.72+/-1.54%) and CCR2 (11.54+/-4.65% versus 1.52+/-1.29%; P<0.05) were observed in IE patients compared to controls. Expression levels of MCP1 (R=0.867) and CCR2 (R=0.835) in IE patients with HS were correlated with the disease duration. However, no correlation was found in IE patients without HS. There was also no correlation between levels of MCP1 and CCR2 in IE patients with age, either with HS or without HS. These results suggest that MCP1 and its receptor may play a role in the pathogenesis and progression of IE. PMID- 26810468 TI - Bone invasiveness is associated with prognosis in clivus chordomas. AB - Clivus chordomas present a great challenge for neurosurgeons, and the prognosis is poor. To investigate bone invasiveness characteristics in regard to the prognosis of clivus chordomas, a retrospective study of 19 patients with primary clivus chordoma was performed. Clinical data, MRI, CT scans and follow-up data were examined, and the bone invasiveness of the chordoma was classified into two growth patterns (endophytic and exophytic) which were analyzed with regard to prognosis. The overall survival rate was 78.9% with radical surgery and adjuvant radiation, with a mean follow-up of 44.5months. There were 12 patients in the endophytic group and seven in the exophytic group, and the exophytic group exhibited a higher recurrence rate than the endophytic group (p=0.006). Chordomas with an exophytic growth pattern were more likely to recur than those with an endophytic growth pattern, and the surgical approach can be tailored according to each growth pattern. PMID- 26810470 TI - Role and mechanism of microRNA-21 in H2O2-induced apoptosis in bone marrow mesenchymal stem cells. AB - microRNA-21 (miR-21) contributes to anti-apoptosis, proliferation and migration in many cells, but its role in inhibiting apoptosis in bone marrow mesenchymal stem cells (BMSC) remains unclear. The aim of this study was to determine the role of miR-21 in H2O2-induced BMSC apoptosis. We used quantitative real time polymerase chain reaction (RT-PCR) to demonstrate the level of miR-21 after treatment of BMSC with H2O2. BMSC apoptosis was induced by different concentrations of H2O2 and was decreased in miR-21-upregulated cells. The expression of PTEN, a functional target gene of miR-21 in BMSC, was regulated by miR-21. The RT-PCR results indicated that miR-21 was significantly up-regulated, and western blot analysis indicated that Bcl-2 was up-regulated, whereas the apoptosis-related genes caspase 3/9 and Bax were down-regulated in miR-21-up regulated cells. The miR-21-up-regulated cells had significantly enhanced Akt phosphorylation, as measured by western blot analysis. LY294002, an inhibitor of Akt activation, abolished the protective effects of miR-21-up-regulated cells. These results suggest that miR-21 contributes to inhibition of apoptosis in BMSC by down-regulating PTEN, potentially via the PI3K/Akt pathway. PMID- 26810472 TI - Attributions, future time perspective and career maturity in nursing undergraduates: correlational study design. AB - BACKGROUND: Career maturity is an important parameter as nursing undergraduates prepare for their future careers. However, little is known regarding the relationships between attributions, future time perspective and career maturity among nursing undergraduates. The purpose of this study was to investigate the degree of career maturity and its relationship with attributions and future time perspective. METHODS: A cross-sectional survey was designed. This survey was administered to 431 Chinese nursing undergraduates. Independent-sample t-tests and one-way ANOVA were performed to examine the mean differences between categories of binary and categorical demographic characteristics, respectively. Pearson correlations and multiple linear regressions were used to test the relationships between attributions, future time perspective and career maturity. RESULTS: The degree of career maturity was moderate among nursing undergraduates and that internal attributions of academic achievement, future efficacy and future purpose consciousness were positively associated with career maturity (all p < 0.01). These three factors accounted for 37.6% of the variance in career maturity (adjusted R(2) = 0.376). CONCLUSIONS: These findings might assist nursing educators and career counselors to improve nursing undergraduate career maturity by elucidating the imperative roles of internal attributions and future time perspective and to facilitate their transition from school to clinical practice. PMID- 26810473 TI - Treatment and survival of supratentorial and posterior fossa ependymomas in adults. AB - Ependymoma is a rare primary brain or spinal cord tumor that arises from the ependyma, a tissue of the central nervous system. This study analyzed a large cohort of adult supratentorial and posterior fossa ependymoma tumors in order to elucidate factors associated with overall survival. We utilized the USA National Cancer Database to study adult World Health Organization grade II/III supratentorial and posterior fossa ependymoma patients treated between 1998 and 2011. Overall survival was estimated by the Kaplan-Meier method and factors associated with survival were determined using a multivariate Cox proportional hazards model. Among 1318 patients, 1055 (80.0%) had grade II and 263 (20.0%) anaplastic tumors located in the posterior fossa (64.3%) and supratentorial region (35.7%). Overall average age was 44.3years, 48.0% of patients were female, 86.5% were Caucasian, and 36.8% underwent near/gross total surgical resection. Radiotherapy was given to 662 patients (50.8%) and 75 (5.9%) received chemotherapy. Older age at diagnosis (hazard ratio [HR] 1.51, p<0.0001), high tumor grade (HR 1.82, p=0.005), and large tumor size (HR 1.66, p=0.008) were associated with poor survival. Females compared to males (HR 0.67, p=0.03) and patients with posterior fossa tumors versus supratentorial (HR 0.64, p=0.04) had a survival advantage. Our study showed that older patients, with supratentorial tumors, and high histological grade had an increased risk of mortality. A survival benefit was captured in females and patients with posterior fossa tumors. Adjuvant radiotherapy and chemotherapy did not confer a survival benefit among all patients, even after stratification by tumor grade or anatomical location. PMID- 26810475 TI - Erratum to: A commentary on the 2015 Canadian Clinical Practice Guidelines in glutamine supplementation to parenteral nutrition. PMID- 26810476 TI - Uninterrupted New Oral Anticoagulants Compared With Uninterrupted Vitamin K Antagonists in Ablation of Atrial Fibrillation: A Meta-analysis. AB - BACKGROUND: Use of uninterrupted vitamin K antagonists (VKAs) during ablation of atrial fibrillation is superior to bridging with heparin. Few studies evaluated the use of uninterrupted new oral anticoagulants (NOACs) during ablation of atrial fibrillation. These studies are relatively small in size and mostly underpowered to show differences in the infrequent thromboembolic complications between comparators. METHODS: We performed the first meta-analysis of uninterrupted NOAC compared with uninterrupted VKA in ablation of atrial fibrillation. We searched the online databases until May 2015 and report outcomes of interest as odds ratios (ORs) using a random effects model. A total of 3544 atrial fibrillation patients in 8 studies who underwent catheter ablation were included in this analysis. RESULTS: Overall, stroke and/or transient ischemic attack events were of very low incidence with uninterrupted anticoagulation strategy in 6 of 3544. There were no differences in rates of stroke and/or transient ischemic attack between uninterrupted NOAC and uninterrupted VKA, 0.11% vs 0.22% (OR, 0.65; 95% confidence interval [CI], 0.14-2.96; P = 0.58), nor in major bleeding 0.9% vs 1% (OR, 0.94; 95% CI, 0.48-1.87; P = 0.87). All bleeding 6.5% vs 7.3% (OR, 0.93; 95% CI, 0.67-1.29; P = 0.65), minor bleeding 6.3% vs 7.1% (OR, 0.93; 95% CI, 0.67-1.28), and cardiac tamponade 0.6% vs 0.6% (OR, 1.0; 95% CI, 0.43-2.31; P = 1.0) were all equal with uninterrupted NOACs compared with uninterrupted VKAs. Among 3544 patients, only one death occurred in the VKA group. CONCLUSIONS: Use of uninterrupted NOACs in ablation appears to be as safe and efficacious as use of uninterrupted VKAs. PMID- 26810478 TI - Low autophagy capacity implicated in motor system vulnerability to mutant superoxide dismutase. AB - INTRODUCTION: The motor system is selectively vulnerable to mutations in the ubiquitously expressed aggregation-prone enzyme superoxide dismutase-1 (SOD1). RESULTS: Autophagy clears aggregates, and factors involved in the process were analyzed in multiple areas of the CNS from human control subjects (n = 10) and amyotrophic lateral sclerosis (ALS) patients (n = 18) with or without SOD1 mutations. In control subjects, the key regulatory protein Beclin 1 and downstream factors were remarkably scarce in spinal motor areas. In ALS patients, there was evidence of moderate autophagy activation and also dysregulation. These changes were largest in SOD1 mutation carriers. To explore consequences of low autophagy capacity, effects of a heterozygous deletion of Beclin 1 were examined in ALS mouse models expressing mutant SOD1s. This caused earlier SOD1 aggregation, onset of symptoms, motor neuron loss, and a markedly shortened survival. In contrast, the levels of soluble misfolded SOD1 species were reduced. CONCLUSIONS: The findings suggest that an inherent low autophagy capacity might cause the vulnerability of the motor system, and that SOD1 aggregation plays a crucial role in the pathogenesis. PMID- 26810481 TI - Synbiotics for Prevention and Treatment of Atopic Dermatitis: A Meta-analysis of Randomized Clinical Trials. AB - IMPORTANCE: Atopic dermatitis (AD) is a highly prevalent condition that may be associated with an altered gastrointestinal microbiota that promotes an immune environment more susceptible to allergic disease. Synbiotics, a mixture of prebiotics and probiotics, have been used for the prevention and treatment of AD. OBJECTIVE: To investigate the efficacy of synbiotics for primary prevention and treatment of AD. DATA SOURCES: PubMed/MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the CAB Abstracts Archive searchable database were searched from the inception of all databases to October 15, 2015, with no language restrictions. STUDY SELECTION: We included all published randomized clinical trials of synbiotics for prevention and/or treatment of AD. To be included, a publication needed to clearly define the intervention as oral administration of synbiotics (combination of probiotics and prebiotics) and must have included an assessment of AD disease severity, such as the Severity Scoring of Atopic Dermatitis (SCORAD) index, or the incidence of AD as an outcome measure. Only 8 of 257 initially identified studies (3%) met selection criteria. DATA EXTRACTION AND SYNTHESIS: Data extraction was independently done by multiple observers and cross-checked to avoid errors. The quality of the selected studies was critically examined following the Cochrane guidelines. Data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES: The primary outcomes were the SCORAD index (treatment studies) and the relative risk of AD (prevention studies). The hypothesis was formulated before data collection. RESULTS: A total of 257 abstracts were screened to identify 6 treatment studies (369 children enrolled; aged 0 months to 14 years) and 2 prevention studies (1320 children enrolled; up to age 6 months in one study and term neonates aged <3 days in the other). From the 6 treatment studies included for random-effects meta-analysis, the overall pooled change in SCORAD index in those treated with synbiotics at 8 weeks of treatment was -6.56 (95% CI, -11.43 to -1.68; P = .008). Heterogeneity was significant (I(2) = 77.1%; P = .001). Subgroup analysis showed that the beneficial effect was significant only when using mixed strains of bacteria (weighted mean difference, -7.32; 95% CI, -13.98 to -0.66; P = .03) and when used in children aged 1 year or older (weighted mean difference, -7.37; 95% CI, -14.66 to -0.07; P = .048). From the 2 prevention studies included, the pooled relative risk ratio of AD in those treated with synbiotics compared with placebo was 0.44 (95% CI, 0.11 to 1.83; P = .26). CONCLUSIONS AND RELEVANCE: This meta-analysis shows evidence that supports the use of synbiotics for the treatment of AD, particularly synbiotics with mixed strains of bacteria and for children aged 1 year or older. Further studies are needed to evaluate the effectiveness of synbiotics for primary prevention of AD. PMID- 26810479 TI - RNA-seq analysis of the gonadal transcriptome during Alligator mississippiensis temperature-dependent sex determination and differentiation. AB - BACKGROUND: The American alligator (Alligator mississippiensis) displays temperature-dependent sex determination (TSD), in which incubation temperature during embryonic development determines the sexual fate of the individual. However, the molecular mechanisms governing this process remain a mystery, including the influence of initial environmental temperature on the comprehensive gonadal gene expression patterns occurring during TSD. RESULTS: Our characterization of transcriptomes during alligator TSD allowed us to identify novel candidate genes involved in TSD initiation. High-throughput RNA sequencing (RNA-seq) was performed on gonads collected from A. mississippiensis embryos incubated at both a male and a female producing temperature (33.5 degrees C and 30 degrees C, respectively) in a time series during sexual development. RNA-seq yielded 375.2 million paired-end reads, which were mapped and assembled, and used to characterize differential gene expression. Changes in the transcriptome occurring as a function of both development and sexual differentiation were extensively profiled. Forty-one differentially expressed genes were detected in response to incubation at male producing temperature, and included genes such as Wnt signaling factor WNT11, histone demethylase KDM6B, and transcription factor C/EBPA. Furthermore, comparative analysis of development- and sex-dependent differential gene expression revealed 230 candidate genes involved in alligator sex determination and differentiation, and early details of the suspected male fate commitment were profiled. We also discovered sexually dimorphic expression of uncharacterized ncRNAs and other novel elements, such as unique expression patterns of HEMGN and ARX. Twenty-five of the differentially expressed genes identified in our analysis were putative transcriptional regulators, among which were MYBL2, MYCL, and HOXC10, in addition to conventional sex differentiation genes such as SOX9, and FOXL2. Inferred gene regulatory network was constructed, and the gene-gene and temperature-gene interactions were predicted. CONCLUSIONS: Gonadal global gene expression kinetics during sex determination has been extensively profiled for the first time in a TSD species. These findings provide insights into the genetic framework underlying TSD, and expand our current understanding of the developmental fate pathways during vertebrate sex determination. PMID- 26810482 TI - Decision conflict and regret among surrogate decision makers in the medical intensive care unit. AB - INTRODUCTION: Family members of critically ill patients in the intensive care unit face significant morbidity. It may be the decision-making process that plays a significant role in the psychological morbidity associated with being a surrogate in the ICU. We hypothesize that family members facing end-of-life decisions will have more decisional conflict and decisional regret than those facing non-end-of-life decisions. METHODS: We enrolled a sample of adult patients and their surrogates in a tertiary care, academic medical intensive care unit. We queried the surrogates regarding decisions they had made on behalf of the patient and assessed decision conflict. We then contacted the family member again to assess decision regret. RESULTS: Forty (95%) of 42 surrogates were able to identify at least 1 decision they had made on behalf of the patient. End-of-life decisions (defined as do not resuscitate [DNR]/do not intubate [DNI] or continuation of life support) accounted for 19 of 40 decisions (47.5%). Overall, the average Decision Conflict Scale (DCS) score was 21.9 of 100 (range 0-100, with 0 being little decisional conflict and 100 being great decisional conflict). The average DCS score for families facing end-of-life decisions was 25.5 compared with 18.7 for all other decisions. Those facing end-of-life decisions scored higher on the uncertainty subscale (subset of DCS questions that indicates level of certainty regarding decision) with a mean score of 43.4 compared with all other decisions with a mean score of 27.0. Overall, very few surrogates experienced decisional regret with an average DRS score of 13.4 of 100. CONCLUSIONS: Nearly all surrogates enrolled were faced with decision-making responsibilities on behalf of his or her critically ill family member. In our small pilot study, we found more decisional conflict in those surrogates facing end-of-life decisions, specifically on the subset of questions dealing with uncertainty. Surrogates report low levels of decisional regret. PMID- 26810483 TI - Markers of endothelial damage and coagulation impairment in patients with severe sepsis resuscitated with hydroxyethyl starch 130/0.42 vs Ringer acetate. AB - PURPOSE: The Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial showed increased mortality in patients resuscitated with hydroxyethyl starch 130/0.42 (HES) vs Ringer acetate. Different effects of the fluids on the endothelium may have contributed to the observed outcome. We aimed to investigate associations between HES vs Ringer and changes in plasma biomarkers reflecting endothelial damage and coagulation impairment. MATERIALS AND METHODS: Six biomarkers, including soluble thrombomodulin (sTM) and plasminogen activator inhibitor 1 (PAI 1), were assessed in a subgroup of 208 patients from the 6S trial. We analyzed differences in plasma concentration in the 2 intervention groups using linear or logistic regression models. RESULTS: The increase in plasma sTM was lower in the HES group (-1.8 ng/mL; 95% confidence interval, -2.9 to -0.7; P = .002). The change was not statistically significant associated with mortality whereas increase in plasminogen activator inhibitor 1 was (odds ratio for 1-unit increase, 1.04; 95% confidence interval, 1.01-1.08; P = .01). CONCLUSIONS: Resuscitation with HES vs Ringer decreased early endothelial damage. Although this finding should be interpreted with caution, it indicates that the increased mortality observed with HES in the 6S trial may not be explained by endothelial damage and it emphasizes the challenge of using surrogate markers as outcome. PMID- 26810484 TI - Intraoperative baseline oxygen consumption as a prognostic factor in emergency open abdominal surgery. AB - BACKGROUND: A new anesthesia system, the E-CAIOVX (GE Healthcare) enables the continuous monitoring of oxygen consumption (VO2) and carbon dioxide elimination (VCO2) during the surgical operation. The aim of this study was to evaluate the prognostic role of intraoperative baseline VO2 and VCO2 in an emergency open abdominal operation. METHODS: A total of 103 patients who had an emergency open abdominal operation were enrolled in the study. VO2 and VCO2 were continuously measured from the induction of anesthesia to the end of the operation. RESULTS: There were significant correlations between intraoperative baseline VO2 and body surface area (BSA; P < .001, r = 0.68), VO2 and tidal volume (P < .001, r = 0.59), and VO2 and baseline body temperature (P < .0001, r = 0.49). Also, there were significant correlations between intraoperative baseline VCO2 and BSA (P < .001, r = 0.70), VCO2 and tidal volume (P < .001, r = 0.70), and VCO2 and body temperature (P < .001, r = 0.41). Fifteen (14.6%) of the 103 patients died within 4 months after the operation without having been discharged from hospital. Baseline VO2/BSA was higher in surviving patients (123.7 +/- 23.6 mL/min ? m(2)) than the deceased (103.8 +/- 15.6 mL/min ? m(2); P = .002). There was no significant difference in baseline VCO2/BSA levels between surviving (106.2 +/- 20.1 mL/min ? m(2)) and deceased patients (99.4 +/- 21.4 mL/min ? m(2)). In multivariate analysis, baseline body temperature lower than 36.2 degrees C (P = .02), serum albumin less than 3.0 g/dL (P = .002), and baseline VO2/BSA less than 111.9 mL/min ? m(2) (P = .03) were independent factors. CONCLUSION: Baseline low VO2/BSA less than 111.9 mL/min ? m(2) was one of the poor predictors for the prognosis of an emergency open abdominal surgery. PMID- 26810486 TI - Tautomerism in 8-Nitroguanosine Studied by NMR and Theoretical Calculations. AB - The guanine base in DNA, due to its low oxidation potential, is particularly sensitive to chemical modifications. A large number of guanine lesions have been characterized and studied in some detail due to their relationship with tissue inflammations. Nevertheless, one example of these lesions is the formation of 8 nitro-guanosine, but the NMR data of this compound was only partially interpreted. A comprehensive study of the two possible tautomeric forms, through a detailed characterization of this compound, has implications for its base pairing properties. The target compound was obtained through a synthetic sequence of five steps, where all intermediates were fully characterized using spectral data. The analysis of the two tautomers was then evaluated through NMR spectroscopy and theoretical calculations of the chemical shifts and NH coupling constants, which were also compared with the data from guanosine. PMID- 26810485 TI - Routine immunization of adults by pharmacists: Attitudes and beliefs of the Canadian public and health care providers. AB - Vaccine coverage among adults for recommended vaccines is generally low. In Canada and the US, pharmacists are increasingly becoming involved in the administration of vaccines to adults. This study measured the knowledge, attitudes, beliefs, and behaviors of Canadian adults and health care providers regarding pharmacists as immunizers. Geographically representative samples of Canadian adults (n = 4023) and health care providers (n = 1167) were surveyed, and 8 focus groups each were conducted nationwide with adults and health care providers. Provision of vaccines by pharmacists was supported by 64.6% of the public, 82.3% of pharmacists, 57.4% of nurses, and 38.9% of physicians; 45.7% of physicians opposed pharmacist-delivered vaccination. Pharmacists were considered a trusted source of vaccination information by 75.0% of the public, exceeding public health officials (68.3%) and exceeded only by doctors and nurses (89.2%). Public concerns about vaccination in pharmacies centered on safety (management of adverse events), record keeping (ensuring their family physician was informed), and cost (should be no more expensive than vaccination at public health or physicians' offices). Concerns about the logistics of vaccination delivery were expressed more frequently in regions where pharmacists were not yet immunizing than in jurisdictions with existing pharmacist vaccination programs. These results suggest that the expansion of pharmacists' scope of practice to include delivery of adult vaccinations is generally accepted by Canadian health care providers and the public. Acceptance of this expanded scope of pharmacist practice may contribute to improvements in vaccine coverage rates by improving vaccine accessibility. PMID- 26810487 TI - The burden of headache disorders in Nepal: estimates from a population-based survey. AB - BACKGROUND: Headache disorders, particularly migraine and tension-type headache (TTH), are among the most prevalent global public-health problems. Medication overuse headache (MOH) is a common sequela of mismanagement of these. Migraine and MOH are highly disabling. Formulation of responsive health policy requires reliable, locally-derived, population-based data describing both individual and societal impact of headache disorders. South-East Asia is the only one of WHO's six world regions in which no such national data have yet been gathered. METHODS: In a nationwide population-based cross-sectional study, a representative sample of Nepalese-speaking adults (18-65 years) were randomly selected by stratified multistage cluster sampling. Trained interviewers made unannounced door-to-door visits and enquired into headache and its attributable burden using a culturally adapted and validated Nepalese translation of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire. RESULTS: Among 2100 participants, 1794 (85.4 %) reported headache during the preceding year (male: 689 [38.4 %], female 1105 [61.6 %]; mean age 36.1 +/- 12.6 years). Mean headache frequency was 3.8 +/- 6.2 days/month, mean headache intensity 2.1 +/- 0.7 on a 0-3 scale, and mean attack duration 41.9 +/- 108.5 h. All aspects of symptom burden (frequency, intensity and duration) were greater among females (p < 0.001). Participants with headache had poorer quality of life (QoL) than those without (p < 0.001); QoL was worst among those with probable MOH (pMOH). Mean proportions of total available time spent in the ictal state were 5.4 % among participants with migraine, 3.9 % among those with TTH and 44.7 % among those with pMOH, with headache-related disabilities of 2.4, 0.15 and 9.7 % respectively. At population level, these disorders were responsible for reduced functional capacities of 0.81, 0.06 and 0.20 %. Total lost productive time due to headache was 6.8 % for the 85 % of the population with headache. Males lost more paid worktime than females (p < 0.001); the reverse was so for household worktime (p < 0.001). CONCLUSIONS: Headache disorders, very common in Nepal, are also highly burdensome at both individual and population levels. There is a substantial penalty in lost production. The remedy lies in better health care for headache; structured headache-care services are urgently needed in the country, and likely to be cost-saving. PMID- 26810488 TI - The times they are a-changin': Two-dimensional aortic valve measurements differ throughout diastole. AB - INTRODUCTION: Diastolic aortic valve measurements are used to obtain weight independent cardiac ratiometric indices. However, whether clinically important variations in valve measurements occur during diastole remains undetermined. ANIMALS: One hundred sixty-three dogs and 40 cats; a mixture of healthy animals and patients with heart disease. MATERIALS AND METHODS: Aortic valve diameter and area were measured at three time-points: early diastole {AoMAX}, during the P wave {AoP} and at end-diastole {AoMIN}. Measurement beat-to-beat variability was determined. Difference plots were generated for each measurement pair. Aortic measurements were compared by repeated measures analysis of variance. RESULTS: In dogs, normalised aortic diameters showed a fixed bias of approximately 14% for AoMAX-AoMIN, 6% for AoMAX-AoP and 8% for AoP-AoMIN. In cats, the aortic diameter and area biases were all less than 2.5% and less than 7% respectively. AoMAX was the largest measurement in 78% patients and AoMIN was the smallest measurement in 73% patients. In dogs, AoMAX > AoP > AoMIN (p < 0.0001). Median within-patient measurement variability was 5% for linear dimensions and 8% for area measurements in dogs and 4.5% for linear and 10.4% for area in cats. DISCUSSION: Aortic measurements in dogs differ significantly throughout diastole, with Ao(A)MAX > Ao(A)P > Ao(A)MIN. These differences could clinically impact cardiac ratiometric indices. The difference in cats is less than the within-patient measurement variability and unlikely to be of clinical significance. CONCLUSIONS: Operators should adopt a single diastolic time-point for measurement of the aorta to ensure consistency in measuring and reporting in echocardiography. PMID- 26810489 TI - Standardization of the two-dimensional transcoelomic echocardiographic examination in the central bearded dragon (Pogona vitticeps). AB - OBJECTIVES: To objectively and subjectively describe the normal spectrum of two dimensional echocardiographic findings in the central bearded dragon (Pogona vitticeps). ANIMALS: Sixteen central bearded dragons. METHODS: Central bearded dragons were prospectively evaluated under manual restraint in right and left lateral recumbency to identify imaging planes for reproducible measurements of cardiac chambers, subjective two-dimensional analysis and color Doppler assessment. RESULTS: Echocardiography can be performed through windows in the left and right axillae. The window in the left axilla allows for a subjective and objective assessment of cardiac structure and function. The right axillary window allows for evaluation of pulmonary artery flow. Both views provide data for the presence of pericardial effusion or valvular insufficiency. With optimized imaging planes, cardiac chambers and fractional area change along with fractional shortening in the longitudinal and transverse planes can be calculated. Body weight and cardiac chamber dimensions of males were significantly larger than females. Ventricular fractional area change was the most consistent functional assessment. The majority of animals were found to have no evidence of valvular insufficiency, while approximately half had evidence of pericardial fluid. Pulmonary artery flow was assessed in all patients. Left and right aortic velocities cannot be reliably obtained. CONCLUSIONS: This study is the first to generate reference values for cardiac structure and function in clinically healthy central bearded dragons. Valvular insufficiency is not a normal finding in central bearded dragons, while mild pericardial effusion may be. PMID- 26810491 TI - Development and Characterization of Nisin Nanoparticles as Potential Alternative for the Recurrent Vaginal Candidiasis Treatment. AB - The aim of this work was the development and characterization of nisin-loaded nanoparticles and the evaluation of its potential antifungal activity. Candidiasis is a fungal infection caused by Candida sp. considered as one of the major public health problem currently. The discovery of antifungal agents that present a reduced or null resistance of Candida sp. and the development of more efficient drug release mechanisms are necessary for the improvement of candidiasis treatment. Nisin, a bacteriocin commercially available for more than 50 years, exhibits antibacterial action in food products with potential antifungal activity. Among several alternatives used to modulate antifungal activity of bacteriocins, polymeric nanoparticles have received great attention due to an effective drug release control and reduction of therapeutic dose, besides the minimization of adverse effects by the preferential accumulation in specific tissues. The nisin nanoparticles were prepared by double emulsification and solvent evaporation methods. Nanoparticles were characterized by dynamic light scattering, zeta potential, Fourier transform infrared, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy. Antifungal activity was accessed by pour plate method and cell counting using Candida albicans strains. The in vitro release profile and in vitro permeation studies were performed using dialysis bag method and pig vaginal mucosa in Franz diffusion cell, respectively. The results revealed nisin nanoparticles (300 nm) with spherical shape and high loading efficiency (93.88 +/- 3.26%). In vitro test results suggest a promising application of these nanosystems as a prophylactic agent in recurrent vulvovaginal candidiasis and other gynecological diseases. PMID- 26810492 TI - LINE-1 silencing by retinoblastoma proteins is effected through the nucleosomal and remodeling deacetylase multiprotein complex. AB - BACKGROUND: Long Interspersed Nuclear Element-1 (L1) is an oncogenic mammalian retroelement silenced early in development via tightly controlled epigenetic mechanisms. We have previously shown that the regulatory region of human and murine L1s interact with retinoblastoma (RB) proteins to effect retroelement silencing. The present studies were conducted to identify the corepressor complex responsible for RB-mediated silencing of L1. METHODS: Chromatin immunoprecipitation and silencing RNA technology were used to identify the repressor complex that silences L1 in human and murine cells. RESULTS: Components of the Nucleosomal and Remodeling Deacetylase (NuRD) multiprotein complex specifically enriched the L1 5'-untranslated DNA sequence in human and murine cells. Genetic ablation of RB proteins in murine cells destabilized interactions within the NuRD macromolecular complex and mediated nuclear rearrangement of Mi2 beta, an ATP-dependent helicase subunit with nucleosome remodeling activity. Depletion of Mi2-beta, RbAP46 and HDAC2 reduced the repressor activity of the NuRD complex and reactivated a synthetic L1 reporter in human cells. Epigenetic reactivation of L1 in RB-null cells by DNA damage was markedly enhanced compared to wild type cells. CONCLUSIONS: RB proteins stabilize interactions of the NuRD corepressor complex within the L1 promoter to effect L1 silencing. L1 retroelements may serve as a scaffold on which RB builds heterochromatic regions that regulate chromatin function. PMID- 26810493 TI - Racial disparity in adherence to positive airway pressure among US veterans. AB - PURPOSE: Despite advances in continuous positive airway pressure (CPAP) technology, compliance with CPAP therapy remains suboptimal. Studies conducted since the advent of objective CPAP recording have noted that African Americans (AA) may use CPAP less than Whites. We sought to confirm this finding among a large sample of veterans and examine effect modifiers of the differential usage. METHODS: A retrospective cohort of 233 AA and 1939 White Veterans Administration (VA) patients who had a sleep study between January 2003 and October 2006 and received CPAP therapy by the end of 2007. CPAP compliance was summarized at 2 weeks and 6 months post CPAP receipt. RESULTS: AAs were significantly less adherent than Whites even when controlling for age, gender, marital status, median household income for zip code, BMI, comorbidities, and obstructive sleep apnea (OSA) severity. AAs with severe OSA were 3 times more likely to use CPAP than AAs with mild/moderate OSA (p <= 0.001); a much smaller but still statistically significant difference was seen for Whites. CONCLUSIONS: CPAP compliance is considerably lower in AAs than in Whites, though severity of OSA modifies this association. These findings are not readily explained by differences in demographics or comorbidity. PMID- 26810494 TI - Association between continuous positive airway pressure and circulating omentin levels in patients with obstructive sleep apnoea. AB - PURPOSE: Inflammation and oxidative stress play important roles in the pathogenesis of obstructive sleep apnoea syndrome (OSAS). Omentin is expressed in visceral adipose tissue and is associated with the inflammatory response. The aim of this study was to assess the relationship between OSAS and omentin based on a comparison of its serum levels at baseline and after 3 months of continuous positive airway pressure (CPAP) therapy. METHODS: Ninety-six newly diagnosed OSAS patients and 31 non-apnoeic controls were enrolled in this study. Blood samples were obtained in the morning after polysomnography. Within the OSAS group, 30 patients were started on CPAP therapy and then reassessed clinically, including a blood test for serum omentin and other biochemical analysis, at 3 months. RESULTS: Serum omentin levels were significantly lower in the OSAS group than in the control group (27.7 +/- 7.6 and 42.5 +/- 5.2 ng/mL, P < 0.001). In the subgroup analysis, omentin concentrations were significantly lower in patients with severe OSAS than in those with mild/moderate OSAS (P < 0.001). Circulating omentin levels were significantly correlated with the apnoea-hypopnoea index (AHI), mean SaO2, oxygen desaturation index, and serum C-reactive protein levels. Treatment with CPAP resulted in a significant increase in circulating omentin levels after 3 months, from 22.7 +/- 1.4 to 41.2 +/- 3.3 ng/mL (P < 0.001). CONCLUSIONS: OSAS is associated with low serum omentin levels, and these levels can be reversed by effective CPAP treatment. PMID- 26810495 TI - Three-dimensional assessment of anatomical balance and oral appliance treatment outcome in obstructive sleep apnoea. AB - PURPOSE: Mandibular advancement splints (MAS) are an effective treatment for obstructive sleep apnoea (OSA). However, MAS are not equally efficacious across all patients and the reasons are not well understood. Craniofacial and upper airway structure individually influence MAS response. We aimed to assess anatomical balance, defined as the ratio of upper airway soft tissue (ST) volume to maxillomandibular enclosure volume, between MAS treatment responders and non responders. METHODS: OSA patients (apnoea-hypopnea index (AHI) >10 h(-1)) were recruited for MAS treatment. Magnetic resonance imaging of the upper airway was performed during wakefulness without and with MAS in situ. Images were processed for volumetric analysis of upper airway soft tissues (tongue, soft palate, paraphayrngeal fat pads and lateral pharyngeal walls) and three-dimensional cephalometry to acquire intra-mandibular space area (IMA) and total maxillomandibular (Mm) volume. Anatomical balance ratios were compared between MAS treatment responders (AHI <10 h(-1) + 50 % reduction) and non-responders. RESULTS: Image analysis was completed in 69 patients (68 % male, age 50.5 +/- 10.1 years, BMI 29.6 +/- 5.0 kgm(2), AHI 27.0 +/- 14.7 h(-1)) including 36 responders. Soft tissue volumes did not differ between MAS responders and non responders. Non-responders had increased ST/IMA compared to responders (4.9 +/- 0.6 vs. 4.6 +/- 0.6, p = 0.031). In multivariate logistic regression with AHI and BMI, ST/IMA was the only predictive variable (p = 0.036, ROC AUC 0.7). However, changes in ST/Mm did not directly relate to treatment response. CONCLUSIONS: Anatomical imbalance assessed by intra-mandibular space area was associated with poor MAS treatment response. However, changes in anatomical balance with mandibular advancement did not reflect treatment outcome as static imaging may not adequately capture improvements in upper airway function. PMID- 26810496 TI - An oral appliance with or without elastic bands to control mouth opening during sleep-a randomized pilot study. AB - BACKGROUND: Oral appliances (OAs) hold the lower jaw forward to reduce obstructive sleep apneas. Some OA designs allow mouth opening, which influences the forward positioning of the lower jaw. The aim of this pilot study was to compare the efficacy of an adjustable, custom-made OA (Narval(r)) in its original design, which allowed mouth opening, with the same OA with elastic bands that restricted mouth opening. METHODS: Consecutive patients with an apnea-hypopnea index (AHI) of >=15 were randomized to start with an OA either with or without elastic bands in a single-blinded, crossover, pilot study. The patients underwent acclimatization and titration. After 3 weeks use of each device, they had renewed sleep apnea recordings and responded to questionnaires. Washout periods took place between the tests. RESULTS: Ten subjects with a median AHI of 19.7 (interquartile range (IQR) 17.3 to 31.8) were included. The AHI decreased to 3.1 (IQR 1.5-14.7) (p < 0.01) with the OA and to 5.1 (IQR 2.4-14.3) (p < 0.01) with the OA with elastic bands, with no difference between them (p = 0.7). The two subjects with severe obstructive sleep apnea (OSA) almost halved their supine AHI with, as compared to without, elastic bands. The majority of the patients preferred to use the elastic bands. CONCLUSIONS: This pilot study indicates that elastic bands markedly reduced the supine AHI in two subjects with severe sleep apnea as compared to without elastic bands. The majority of the patients preferred the use of elastic bands, although no significant difference in the AHI was observed with versus without the elastic bands in the whole sample. PMID- 26810497 TI - Construct validity and factor structure of the Pittsburgh Sleep Quality Index among pregnant women in a Pacific-Northwest cohort. AB - PURPOSE: Poor sleep quality during pregnancy is associated with adverse obstetric and neuropsychiatric outcomes. Despite its routine use as a sleep quality assessment scale among men and non-pregnant women, the psychometric properties of the Pittsburgh Sleep Quality Index (PSQI) have not been assessed among US pregnant women. We sought to evaluate the construct validity and factor structure of the PSQI among 1488 pregnant women. METHODS: A structured interview was used to collect information about demographics and sleep characteristics in early pregnancy. The Patient Health Questionnaire-9 (PHQ-9) and the Depression, Anxiety, and Stress Scale-21 (DASS-21) were used to assess symptoms of depression, anxiety, and stress. Consistency indices, exploratory and confirmatory factor analyses (EFA and CFA), correlations, and logistic regression procedures were used. RESULTS: The reliability coefficient, Cronbach's alpha for the PSQI items was 0.74. Results of the EFA showed that a rotated factor solution for the PSQI contained two factors with eigenvalues >1.0 accounting for 52.8 % of the variance. The PSQI was significantly positively correlated with the PHQ-9 (r s = 0.48) and DASS-21 (r s = 0.42) total scores. Poor sleepers (PSQI global score >5) had increased odds of experiencing depression (OR = 6.47; 95 % CI = 4.56 9.18), anxiety (OR = 3.59; 95 % CI = 2.45-5.26), and stress (OR = 4.37; 95 % CI = 2.88-6.65) demonstrating evidence of good construct validity. CFA results corroborated the two-factor structure finding from the EFA and yielded reassuring measures indicating goodness of fit (comparative fit index = 0.975) and accuracy (root mean square error of approximation = 0.035). CONCLUSIONS: The PSQI has good construct validity and reliability for assessing sleep quality among pregnant women. PMID- 26810498 TI - Early life nutrition and the opportunity to influence long-term health: an Australasian perspective. AB - There are now significant data to support the hypothesis that early life nutrition in the fetus, infant and young child can have profound effects on long term health. This review considers some of this evidence with specific reference to the current burden of disease in Australia and New Zealand. As the findings of further research become available, recommendations on optimizing early life nutrition should be formulated and made widely available as part of the preventative health policy agenda in both Australia and New Zealand. PMID- 26810499 TI - Stent Retrievers for the Treatment of Acute Ischemic Stroke: A Systematic Review and Meta-analysis of Randomized Clinical Trials. AB - IMPORTANCE: Stent retrievers are a promising alternative for the treatment of acute ischemic stroke (AIS). Several recently completed clinical trials have examined the use of stent retrievers with intravenous recombinant tissue plasminogen activator (rtPA) compared with rtPA alone. OBJECTIVE: To conduct a systematic review and meta-analysis of randomized clinical trials to quantify the benefits and risks of using stent retrievers in addition to rtPA for the treatment of AIS. DATA SOURCES: The MEDLINE, EMBASE, and Cochrane Library of Clinical Trials databases were searched from inception to July 2015 for the keywords stent*, retriev*, Solitaire, Trevo, Revive, and stroke. Trial registries were also searched. A total of 326 publications were identified and 213 potentially relevant records were screened. STUDY SELECTION: Randomized clinical trials that examined stent retrievers with rtPA vs rtPA alone were included in the meta-analysis. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted study data and performed quality assessment using the Cochrane Risk of Bias Tool. DerSimonian and Laird random-effects models were used to estimate relative risks (RRs), risk differences (RDs), and numbers needed to treat. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients achieving functional independence (defined as a score of 0-2 on the modified Rankin Scale, with 0 indicating no disability and 6 indicating death) at 90 days. Risks of all-cause mortality, intracranial hemorrhage, and parenchymal hematoma at 90 days were also assessed. RESULTS: Five randomized clinical trials met our inclusion criteria (n = 1287 patients). Patients randomized to stent-retriever therapy with rtPA had significantly improved rates of functional independence at 90 days compared with those randomized to rtPA alone (RR, 1.72; 95% CI, 1.48 1.99; RD, 0.19; 95% CI, 0.13-0.25). When data were pooled across trials, the effect of stent-retriever therapy on all-cause mortality at 90 days was inconclusive (RR, 0.82; 95% CI, 0.60-1.11; RD, -0.04; 95% CI, -0.08 to 0.1). There were similarly no detectable differences in the risks of intracranial hemorrhage (RR, 1.15; 95% CI, 0.67-1.97; RD, 0.00; 95% CI, -0.02 to 0.03) or parenchymal hematoma (RR, 1.18; 95% CI, 0.71-1.94; RD, 0.01; 95% CI, -0.01 to 0.04), although the 95% CIs were wide. Fixed-effects sensitivity analyses produced similar results for all outcomes. CONCLUSIONS AND RELEVANCE: The use of stent retrievers in conjunction with rtPA vs rtPA alone is associated with significant improvement of functional independence 90 days after AIS. PMID- 26810502 TI - Margaret McCartney: Who gains from the media's misrepresentation of science? PMID- 26810501 TI - [Preventing post solid organ transplant tuberculosis with antibiotic prophylaxis]. PMID- 26810504 TI - Impact of leaching conditions on constituents release from Flue Gas Desulfurization Gypsum (FGDG) and FGDG-soil mixture. AB - The interest in using Flue Gas Desulfurization Gypsum (FGDG) for land applications has increased recently. This study evaluates the leaching characteristics of trace elements in "modern" FGDG (produced after fly ash removal) and FGDG-mixed soil (SF) under different environmental conditions using recently approved EPA leaching methods (1313-1316). These methods employ various pH and liquid-solid (LS) ratios under batch leaching, column percolation and diffusion controlled release scenarios. Toxicity Characteristic Leaching Protocol (TCLP) and Synthetic Precipitation Leaching Protocol (SPLP) were used for comparison. The data obtained from new EPA methods provide broad insight into constituent release from FGDG and SF when compared to TCLP and SPLP. The release of toxic elements such as Hg, As, Pb, Co, Cd and Cr from SF was negligible. High release of B from FGDG was observed under all tested conditions; however, its release from SF was low. Both FGDG and SF released Se under all pH conditions (2 13) and LS ratios (1-10) in low concentrations (0.02-0.2mg/L). The data from this study could be used to investigate potential use of "modern" FGDG for new beneficial land applications. PMID- 26810506 TI - Gait variability across the disability spectrum in people with multiple sclerosis. AB - BACKGROUND: An alternative method suggested to assess changes in walking in people with multiple sclerosis (PwMS) is evaluating gait variability. This is a credible option since gait variability reflects to some degree the quality of gait control. OBJECTIVE: Examine the impact of disability on gait variability in PwMS. METHODS: In this cross-sectional study, the data pool was divided into seven levels of disability based on the Expanded Disability Status Scale (EDSS) score, ranging from 0 to 6.5. Gait variability was studied using an electronic mat. RESULTS: The final analysis included 381 PwMS (249 women); mean age 44.0years. Non-significant differences were observed between the EDSS subgroups at the lower end of the spectrum (EDSS 0-3.5) in all gait variability parameters. In contrast, PwMS in the EDSS 5.0-5.5 group demonstrated a significant increase in variability of step length (~151%), single support (~93%) and step time (142%) compared with those who scored 0-3.5. Moreover, participants in the EDSS 5.0-5.5 group had elevated step length variability compared to the EDSS 4.0-4.5 group (9.3 (S.E.=2.2) vs. 5.5 (S.E.=0.4), P-value=0.005). CONCLUSION: We encourage clinicians to follow-up on the gait variability score as it appears to reflect mobility deterioration in PwMS. PMID- 26810507 TI - Thrombolysis for acute stroke in patient with systemic lupus erythematosus: A case report. PMID- 26810508 TI - Two young stroke patients associated with regular intravenous immunoglobulin (IVIg) therapy. AB - We recently experienced 2 young adult patients who developed ischemic stroke after regular intravenous immunoglobulin (IVIg) therapy for agammaglobulinemia with diagnosis of common variable immunodeficiency (CVID) in their childhood. Patient 1 was 26-year-old woman, who developed Wallenberg's syndrome 6 days after the last IVIg therapy, but had no further stroke recurrence with cilostazol later. Patient 2 was 37-year-old man, who developed recurrent cerebral infarction in the territory of bilateral lenticulostriate branches like branch atheromatous disease (BAD) several days after the IVIg therapy. However, he had no further stroke recurrence after bone marrow transplantation (BMT) therapy for his lymphoproliferative disorder. It was suggested that IVIg therapy was associated to these different types of ischemic stroke in our 2 young adult patients with minimal vascular risk factors. Although IVIg therapy is widely used as a relatively safe medication for immunodeficiency disorders or autoimmune diseases, we need to pay more attention to stroke occurrence with regular IVIg therapy. PMID- 26810509 TI - Continuation and adherence rates on initially-prescribed intensive secondary prevention therapy after Rapid Access Stroke Prevention (RASP) service assessment. AB - INTRODUCTION: Consistent adherence to treatment is essential for effective secondary prevention following TIA/ischaemic stroke. Representative data on long term treatment continuation and adherence rates are limited. METHODS: This single centre study recruited patients attending our Rapid Access Stroke Prevention clinic in Ireland from 07/09/2006 -> 30/11/2009. Demographic and clinical data, and prescribed medication regimens at initial assessment were recorded. All patients received copies of clinical correspondence containing clear 'goal directed treatment advice' sent to their general practitioner or referring physician. Patients were subsequently interviewed with a standardised pro-forma to assess continuation and adherence rates; overall adherence rates with secondary prevention therapy were also assessed with a validated self-reporting tool (Morisky Scale). Recurrent vascular events during follow-up were recorded. RESULTS: One hundred and fourteen patients were recruited; mean age: 64.5 +/- 13.8 years; median duration of follow-up: 630 days. Patients were prescribed aspirin (69.3%), alone (17.5%) or in combination with dipyridamole MR (51.8%), clopidogrel (18.2%), warfarin (16.7%), statins (76.3%) and anti-hypertensives (51.8%). During follow-up, the percentages of patients continuing treatment prescribed at the initial visit were: Aspirin (93.7%), dipyridamole MR (72.9%), clopidogrel (81%), warfarin (94.7%), statins (87.9%) and anti-hypertensives (89.8%). Overall, 99.1% reported taking their medication the preceding day. Morisky scale scores for all treatments revealed that 41.2% (N=47) were high, 36.8% (N=42) medium, and 12.3% (N=14) low adherers; 9.7% (N=11) had incomplete data. Two patients (1.8%) had recurrent cerebrovascular events, and two (1.8%) had myocardial infarctions. DISCUSSION: This novel study in European TIA/ischaemic stroke patients, who were provided with a goal-directed secondary prevention plan, showed high rates of medication-continuation and self-reported adherence with prescribed treatment, associated with a low incidence of recurrent vascular events during a median follow up of 1.7 years. PMID- 26810510 TI - Ingested (oral) anti-IL-12/23 inhibits EAE. AB - BACKGROUND: Blocking the activity of IL-12/23 can inhibit autoimmune diseases such as psoriasis. OBJECTIVE: We examined whether an antibody against IL-12/23, ustekinumab (UTZ) (Stelera(r)), used clinically in psoriasis would have similar anti-inflammatory effects in EAE after oral administration. DESIGN/METHODS: B6 mice were immunized with MOG peptide 35-55 and gavaged with isotype IgG control or UTZ during ongoing disease. Splenocytes, CD4(+) T cells or macrophages/monocyte lineage cells (CD11b(+)) from control fed or UTZ fed mice were adoptively transferred into active MOG peptide 35-55 immunized recipient mice during ongoing disease. Actively fed and recipient mice were examined for disease inhibition, inflammation, and cytokine responses. RESULTS: Ingested (oral) UTZ inhibited ongoing disease and decreased inflammation. Adoptively transferred cells from UTZ fed donors protected against actively induced disease and decreased inflammation. Oral UTZ decreased pro-inflammatory cytokines Th1 like cytokines IL-2, IL-12, IFN-gamma, IL-17 (Teff) and TNF-alpha in UTZ fed mice and increased counter-regulatory cytokines IL-4, IL-10 and IL-13 in recipients of donor cells from UTZ fed mice. CONCLUSIONS: Ingested (orally administered) UTZ can inhibit disease, CNS inflammation, decrease pro-inflammatory Th1-like and Th17 cytokines and increase Th2-like anti-inflammatory cytokines. PMID- 26810511 TI - Acute posterior multifocal placoid pigment epitheliopathy presenting with multiple brain and spinal cord infarctions. PMID- 26810512 TI - Rhabdomyolysis featuring muscular dystrophies. AB - BACKGROUND: Rhabdomyolysis is a potentially life threatening condition of various etiology. The association between rhabdomyolysis and muscular dystrophies is under-recognized in clinical practice. OBJECTIVE: To identify muscular dystrophies presenting with rhabdomyolysis at onset or as predominant feature. METHODS: We retrospectively reviewed clinical and laboratory data of patients with a genetically confirmed muscular dystrophy in whom rhabdomyolysis was the presenting or main clinical manifestation. RESULTS: Thirteen unrelated patients (males=6; females=7) were identified. Median age at time of rhabdomyolysis was 18 years (range, 2-47) and median duration between the first episode of rhabdomyolysis and molecular diagnosis was 2 years. Fukutin-related protein (FKRP) muscular dystrophy (n=6) was the most common diagnosis, followed by anoctaminopathy-5 (n=3), calpainopathy-3 (n=2) and dystrophinopathy (n=2). Four patients experienced recurrent rhabdomyolysis. Eight patients were asymptomatic and 3 reported myalgia and exercise intolerance prior to the rhabdomyolysis. Exercise (n=6) and fever (n=4) were common triggers; rhabdomyolysis was unprovoked in 3 patients. Twelve patients required hospitalization. Baseline CK levels were elevated in all patients (median 1200 IU/L; range, 600-3600). CONCLUSION: Muscular dystrophies can present with rhabdomyolysis; FKRP mutations are particularly frequent in causing such complication. A persistently elevated CK level in patients with rhabdomyolysis warrants consideration for underlying muscular dystrophy. PMID- 26810513 TI - Comparison of motor and non-motor features between essential tremor and tremor dominant Parkinson's disease. AB - BACKGROUND: Differential diagnosis of tremor disorders, including essential tremor (ET) and Parkinson's disease-tremor dominant type (PD-TDT), requires further investigation. Therefore, the current study aimed to compare non-motor and tremor features in order to differentiate between ET and PD-TDT. METHODS: Twenty-eight patients with classic ET and 24 patients with typical PD-TDT were retrospectively enrolled in a multi-stage investigation process. Tremor features including surface electromyogram (EMG) were analyzed in detail. For non-motor symptom analyses, the global cognition test, frontal function test, and non-motor symptoms scale (NMSS) were administered, in addition to collecting patient history data. RESULTS: Patients with PD-TDT presented with more asymmetric tremor, whereas patients with ET presented with more symmetric tremor. Leg tremor was observed only in patients with PD-TDT. Surface EMG analyses of arm tremor demonstrated considerable overlaps in tremor type, tremor frequency, and contractive patterns. However, patients with PD-TDT were significantly more likely to exhibit resting tremor, and experienced alternative contraction patterns only for kinetic tremor, which was in contrast to patients with ET. For non-motor symptom analyses, patients with PD-TDT had more non-motor symptoms compared to patients with ET (mean=5.0 vs. 2.6; P=0.002). Specifically, patients with PD-TDT exhibited higher frequencies of hyposmia, REM sleep behavior disorder (RBD)-like symptom, urinary frequency, and memory disturbance. Age- and gender- matched analyses for the severity of NMSS scores did not indicate significant differences. However, patients with PD-TDT displayed slightly lower scores of frontal function test compared to patients with ET. CONCLUSIONS: Careful and detailed evaluations of both tremor features and non-motor symptoms are required in order to distinguish between ET and PD-TDT. PMID- 26810514 TI - Prolonged central sensory conduction time in patients with chronic arsenic exposure. AB - BACKGROUND: Many patients from Toroku, Japan, who have chronic arsenic exposure demonstrate whole-body sensory disturbance that is slightly more pronounced in the extremities. Although previous research in this population showed a mild peripheral neuropathy, it is unknown whether these patients have central nervous system impairment. To investigate the lesion sites underlying sensory disturbance related to chronic arsenic poisoning, we analyzed somatosensory evoked potentials (SEP). METHODS: Clinical features, nerve conduction study results, and median and/or tibial SEP were analyzed in patients with chronic arsenic exposure (total, 13 patients; median & tibial, 4; median, 5; tibial, 4) retrospectively. The SEP findings in patients were compared with those in normal controls. RESULTS: The median SEP results indicated a conduction delay between the proximal brachial plexus and the primary sensory cortex, and tibial SEP findings indicated a delay between the dorsal gray matter of the lumbosacral cord and the primary sensory cortex. CONCLUSION: This is the first study to identify an impairment of the central somatosensory pathway in patients with chronic arsenic exposure. Sensory disturbance in these patients is related not only to peripheral neuropathy but also to impairment of the central nervous system. PMID- 26810515 TI - Cognitive impairment and neurovascular function in patients with severe steno occlusive disease of a main cerebral artery. AB - OBJECTIVE: Patients with severe steno-occlusive disease of a main cerebral artery may demonstrate cognitive impairment without identification of causative lesions on magnetic resonance imaging. We investigated whether cognitive impairment in these patients is associated with regional cerebral blood flow (rCBF), leukoaraiosis, risk factors of atherosclerosis and cerebrovascular reserve (CVR), which shows so-called clinical neurovascular function. METHODS: In 65 patients with severe steno-occlusive disease of an internal carotid artery or a middle cerebral artery (MCA) and no cerebral infarction (CI), we examined cognitive function with COGNISTAT, grades of leukoaraiosis, and CBF and CVR as calculated by iodine-123-N-isopropyl-p-iodoamphetamine single photon emission computed tomography and blood data. We compared such values of the left and right sided diseases. rCBF and CVR on the affected side were compared to other side. RESULTS: Logistic regression analysis revealed that CVR correlated with cognitive impairment. There was no significant difference in rCBF, CVR, or COGNISTAT score when comparing the left and right sided diseases. There were good correlations between CBF or CVR of the ipsilateral MCA area and ipsilateral and contralateral other areas. CONCLUSION: Cognitive impairment is associated with CVR in the whole brain. Nonselective widespread neurovascular mild dysfunction can be a reason for cognitive impairment in patients with severe steno-occlusive disease of a main cerebral artery and no CI. PMID- 26810516 TI - Tumefactive demyelinating brain lesions with multiple closed-ring enhancement in the course of neuromyelitis optica. PMID- 26810517 TI - The association of resting state heart rate variability and 24-hour blood pressure variability in spinal cord injury. AB - Patients with high cervical complete spinal cord injuries (tetraplegia) sustain damage to the autonomic neural pathways that influence cardiovascular functioning and produce variability in the heart rate (HR) and blood pressure (BP). In non injured individuals, an inverse relationship exists between resting autonomic control of the heart (as evidenced by HR variability (HRV)) and BP variability (BPV). This study examined the relationship between HRV, BP and BPV in individuals with tetraplegic (n=10) and paraplegic (n=10) spinal cord injuries, and a group of healthy controls (n=14). Resting HRV at baseline and 24-hour ambulatory BP measurements were collected from electrocardiogram measures of each participant. HRV was quantified using time- and frequency-domain measures. The standard deviation of the BP measurements was used as an index of BPV. Multivariate analyses of variance were performed to examine group differences for laboratory-based and 24-h dependent variables. The MANOVAs for HRV parameters (lambda(14,50)=.352, p=.010, eta(2)=.407) and for BP indices and HR (lambda(16,48)=.318, p=.013, eta(2)=.436) were significant. Furthermore, in line with existing evidence, we found that vagally mediated HRV was inversely related to BPV in healthy controls. However, this relationship did not hold for the tetraplegia group (rho<|.42|), and mixed results were found for the paraplegia group (e.g., rho<|.29| for time domain HRV, rho>|.65| for low-frequency power). These results support the conclusion that the damage to the spinal sympathetic pathways to the heart found in people with tetraplegia causes a significant disruption in baroreflex control of BP. PMID- 26810518 TI - Sphingosine 1-phosphate signaling in astrocytes: Implications for progressive multiple sclerosis. AB - Multiple sclerosis is an autoimmune disorder characterized by recurrent attacks against the central nervous system. After many years, certain patients enter a progressive disease phase, characterized by steady clinical deterioration. However, in 10-15% of patients, the disease is progressive from the beginning, and thus diagnosed as Primary Progressive Multiple Sclerosis. Unlike relapsing remitting forms, progressive MS lacks effective therapy. Astrocytes are a major component of glial cells and are now thought to play a role in disease progression. Sphingosine 1-phophate is a molecule with extensive receptor expression on both immune and glial cells and is also a target of fingolimod, a drug used in relapsing remitting patients that sequesters lymphocytes within lymph nodes. However, because sphingosine 1-phosphate receptors are also expressed in astrocytes, and also because modification of this pathway has shown interesting benefits in animal models of Multiple Sclerosis, this astrocyte pathway has become an interesting target for developing potential new therapeutic approaches for Multiple Sclerosis. PMID- 26810519 TI - Parkinson's Disease--Cognitive Functional Rating Scale across different conditions and degrees of cognitive impairment. AB - BACKGROUND/AIMS: The Parkinson's Disease--Cognitive Functional Rating Scale (PD CFRS) was designed to avoid motor biases in capturing the functional impact of cognitive impairment in Parkinson's disease (PD). Its performance capturing functional impairment in other conditions leading to cognitive dysfunction is unknown. We compare it with non-specific Instrumental Activities of Daily Living scales. METHODS: Two hundred consecutive patients diagnosed in a community hospital with mild cognitive impairment (MCI) [31 MCI-amnestic; 33 MCI-multi domain; 33 PD-MCI] and dementia [35 Alzheimer's disease; 34 vascular dementia; 34 PD with dementia] were assessed on the PD-CFRS, the Blessed Dementia Scale (BDS), the Clinical Dementia Rating--Sum of Boxes (CDR-SOB), and given a comprehensive cognitive assessment. Diagnostic accuracy and optimal cut-off scores were calculated for the PD-CFRS and compared with each functional measure. RESULTS: The PD-CFRS presented high concurrent validity and significant correlation with both BDS and CDR-SOB, and cognitive scores offering a similar discrimination accuracy to non-specific scales [PD-CFRS >= 9 (sensitivity= 0.94; specificity = 0.95)]. No changes appear in cut-off scores when excluding PD patients. Effect size analysis indicated no relevant interference with PD-CFRS scores between the principal cognitive subgroups. DISCUSSION: The findings extend the clinimetric properties of the PD-CFRS and indicate it as an adequate instrument to capture the full spectrum of functional consequences of cognitive decline in the community. PMID- 26810520 TI - Intact emotion recognition and experience but dysfunctional emotion regulation in idiopathic Parkinson's disease. AB - BACKGROUND: A specific non-motor impairment in Parkinson's disease (PD) concerns difficulties to accurately identify facial emotions. Findings are numerous but very inconsistent, ranging from general discrimination deficits to problems for specific emotions up to no impairment at all. By contrast, only a few studies exist about emotion experience, altered affective traits and states in PD. OBJECTIVE: To investigate the decoding capacity for affective facial expressions, affective experience of emotion-eliciting images and affective personality traits in PD. METHODS: The study sample included 25 patients with mild to moderate symptom intensity and 25 healthy controls (HC) of both sexes. The participants were shown pictures of facial expressions depicting disgust, fear, and anger as well as disgusting and fear-relevant scenes. Additionally, they answered self report scales for the assessment of affective traits. RESULTS: PD patients had more problems in controlling anger and disgust feelings than HC. Higher disgust sensitivity in PD was associated with lower functioning in everyday life and lower capacity to recognize angry faces. Furthermore, patients reported less disgust towards poor hygiene and spoiled food and they stated elevated anxiety. However, the clinical group displayed intact facial emotion decoding and emotion experience. Everyday life functionality was lowered in PD and decreased with stronger motor impairment. Furthermore, disease duration was negatively associated to correct classification of angry faces. CONCLUSIONS: Our data indicate that problems with emotion regulation may appear already in earlier disease stages of PD. By contrast, PD patients showed appropriate emotion recognition and experience. However, data also point to a deterioration of emotion recognition capacity with the course of the disease. Compensatory mechanisms in PD patients with less advanced disease are discussed. PMID- 26810521 TI - Ocular motor assessment in concussion: Current status and future directions. AB - Mild head injury such as concussions and subconcussive repetitive impact may lead to subtle changes in brain function and it is imperative to find sensitive and reliable tests to detect such changes. Tests involving the visual system, in particular eye movements, can incorporate higher cortical functioning and involve diffuse pathways in the brain, including many areas susceptible to head impact. With concussions, the clinical neuro-ophthalmic exam is important for detecting abnormalities in vergence, saccades, pursuit, and visual fixation. On the sidelines, the King-Devick test has been used as a visual performance measure that incorporates eye movements and increases the sensitivity in detecting possible concussions in conjunction with standard sideline tests of cognition, symptom checklists, and balance. Much promise lies in the eye movement laboratory to quantitate changes in saccades and pursuit with concussions using video oculography. A combination of eye movement tasks coupled with neuroimaging techniques and other objective biomarkers may lead to a better understanding of the anatomical and physiological consequences of concussion and to better understand the natural history of this condition. PMID- 26810522 TI - Freezing of gait in early Parkinson's disease: Nigral iron content estimated from magnetic resonance imaging. AB - PURPOSE: Freezing of gait is a major source of disability associated with the progression of Parkinson's disease (PD). Our objective was to determine whether evolving changes in nigral iron content in association with declining motor function in early PD differentiates subjects who develop freezing from those who do not. METHODS: A cohort of previously untreated individuals with early PD (n=19) was followed for 36 months clinically and with MRI. The cohort was divided into two groups based on the development of freezing during follow-up. A multiple gradient echo MRI sequence provided an index of basal ganglia iron content. RESULTS: There were significant baseline differences between those who developed freezing (n=7) and those who did not (n=12) in Unified Parkinson's Disease Rating Scale motor scores, time to complete a 14 m walk and timed up and go. There was a significant correlation between the measured change in transverse relaxation in the lateral substantia nigra pars compacta and the change in motor score from baseline to 36 months (p=0.002). The freezing group showed a greater change in motor score and iron content than did the non-freezing group. CONCLUSIONS: Individuals destined to develop freezing early in PD have more motor impairment at baseline, more rapid deterioration in motor function, and pars compacta changes suggestive of increased iron content in comparison to those who do not. PMID- 26810523 TI - Primary cerebellar progressive multifocal leukoencephalopathy (PML) shows increased accumulation in (123)I-IMP SPECT. PMID- 26810524 TI - Step-rate cut-points for physical activity intensity in patients with multiple sclerosis: The effect of disability status. AB - BACKGROUND: Evaluating the relationship between step-rate and rate of oxygen uptake (VO2) may allow for practical physical activity assessment in patients with multiple sclerosis (MS) of differing disability levels. AIMS: To examine whether the VO2 to step-rate relationship during over-ground walking differs across varying disability levels among patients with MS and to develop step-rate thresholds for moderate- and vigorous-intensity physical activity. MATERIALS AND METHODS: Adults with MS (N=58; age: 51 +/- 9 years; 48 women) completed one over ground walking trial at comfortable speed, one at 0.22 m . s(-1) slower, and one at 0.22 m . s(-1) faster. Each trial lasted 6 min. VO2 was measured with portable spirometry and steps with hand-tally. Disability status was classified as mild, moderate, or severe based on Expanded Disability Status Scale scores. RESULTS: Multi-level regression indicated that step-rate, disability status, and height significantly predicted VO2 (p<0.05). Based on this model, we developed step-rate thresholds for activity intensity that vary by disability status and height. A separate regression without height allowed for development of step-rate thresholds that vary only by disability status. CONCLUSION: The VO2 during over ground walking differs among ambulatory patients with MS based on disability level and height, yielding different step-rate thresholds for physical activity intensity. PMID- 26810525 TI - Heme oxygenase-1 dependant pathway contributes to protection by tetramethylpyrazine against chronic hypoxic injury on medulla oblongata in rats. AB - Tetramethylpyrazine (TMP), one of the active ingredients of the Chinese herb Lingusticum Wallichii (Chuan Xiong) has been proved to protect the medulla oblongata from chronic hypoxia injury. However, the underlying mechanism remains unclear. The purpose of this study was to determine whether the protective effects of TMP are associated with the heme oxygenase-1 (HO-1) dependant pathway in adult rats. The morphological changes of neurons in the hypoglossal nucleus (12N), the nucleus ambiguus (Amb), the nucleus tractus solitarius (NTS), and the pre-Botzinger complex (pre-BotC) were investigated by Nissl staining; the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured to evaluate the anti-oxidant effect; some apoptosis parameters, Bax mRNA and Bcl-2 mRNA, were tested; and the double immunochemistry staining of active caspase-3/NeuN was performed. Meanwhile, the HO-1 protein expression and heme oxygenase (HO) activity were examined. Tin-protoporphyrin (SnPP), a potent inhibitor of HO, was used to further confirm the effect of HO-1. We found that TMP ameliorated the neuron loss in 12N, Amb and NTS, the decrease in SOD activity and the increase in MDA content, the decrease in Bcl-2 mRNA of medulla oblongata (P<0.05), and the increase in percentage of apoptotic neurons in Amb (P<0.05) induced by chronic hypoxia. Co-administration with SnPP abolished the beneficial effects above of TMP to some extent (P<0.05). Moreover, TMP significantly increased HO activity and HO-1 protein expression, which was most likely enhanced in the neurons (P<0.05), and co-administration of SnPP reduced these up-regulated effects (P<0.05). This study demonstrated that HO-1 dependant pathway may be involved in the protective action of TMP against chronic hypoxic damage on medulla oblongata in the rats. PMID- 26810527 TI - Clusterin CSF levels in differential diagnosis of neurodegenerative disorders. AB - INTRODUCTION: Clusterin, a heterodimeric glycoprotein, is thought to be involved in many cellular functions, including cell-cell interaction, cell survival and apoptosis. In the brain, post-mortem analysis has found increased clusterin associated with the pathology of many other neurodegenerative diseases (ND) such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), Alzheimer's disease (AD) and multiple system atrophy (MSA). In vivo cerebrospinal fluid (CSF) levels of clusterin in ND diseases may reflect differences in the pathology and thus aid in the differential diagnosis. METHODS: CSF levels of clusterin were assessed in 102 patients with clinical manifestations of neurodegenerative diseases (23 patients with PD, 18 with PDD, 15 with DLB, 18 with AD, 16 with PSP, 12 with MSA) and 21 subjects as a control group (CG). RESULTS: Significantly higher CSF clusterin levels were found in PD compared to CG (median 6884 vs. 4484; p=0.012), DLB (median 6884 vs. 4192; p=0.023), MSA (median 6884 vs. 3606; p=0.001) and PSP (median 6884 vs. 4193; p=0.014). Significantly higher CSF clusterin levels were found in PDD compared to CG (median 8617 vs. 4484; p=0.045), DLB (median 8617 vs. 4192; p=0.025) and MSA (median 8617 vs. 3606; p=0.004). CONCLUSION: The results of the presented "feasibility" study support the role of clusterin in PD/PDD pathogenesis. Clusterin CSF levels could serve as a potential marker for PDD and DLB differentiation. PMID- 26810526 TI - White blood cell count and clinical outcomes after intracerebral hemorrhage: The INTERACT2 trial. AB - BACKGROUND: Increased inflammatory reaction can aggravate brain injury after acute intracerebral hemorrhage, but the clinical effect of such response is not fully understood. The aim of this study was to determine associations of peripheral white blood cell (WBC) count on clinical outcome among participants of the INTERACT2 study. METHODS: INTERACT2 was a randomized controlled trial of early intensive (target systolic level<140 mm Hg) compared to guideline recommended (target systolic level < 180 mm Hg) blood pressure (BP) lowering in 2839 patients with acute ICH (<6h) and elevated systolic BP (150-220 mm Hg). Blood samples were collected on admission and WBC count was measured at local laboratories. The primary outcome was death or major disability, defined by scores 3-6 on the modified Rankin Scale at 90 days. Secondary outcome was death at 90 days. Associations of baseline WBC count and outcomes were evaluated in logistic regression models. INTERACT2 is registered with http://www.clinicaltrials.gov NCT00716079. RESULTS: There were 2630 participants with relevant data who were classified into quartiles of WBC counts (<= 6.22, 6.24-7.89, 7.90-10.17, and >= 10.20 * 10(9)/L, respectively). Increased WBC count was associated with younger age, elevated body temperature, increased glucose level, stroke severity, larger baseline hematoma volume, and intraventricular extension. Risks of death or major disability at 90 days increased progressively with higher WBC count: frequencies of 49.9%, 52.0%, 52.3% and 58.1% for quartile groups, respectively (P=0.004 for trend). However, after adjustment for baseline clinical and imaging variables including age, sex, region, lipid lowering therapy, body temperature, glucose, systolic BP, heart rate, high NIHSS scores, volume and location of hematoma, intraventricular extension, time from onset to CT scan, and randomized treatment, the association between WBC count and primary outcome was no longer significant (P=0.426 for trend). Patients with increased WBC count had significantly higher risk of death (P=0.0003 for trend), but again the association was no longer significant after adjustment for baseline clinical and imaging variables. CONCLUSIONS: Elevated WBC count on admission is not an independent prognostic variable in patients with acute ICH. PMID- 26810528 TI - Sonographic assessment of the optic nerve sheath diameter in the diagnosis of idiopathic intracranial hypertension. AB - OBJECTIVE: Sonographic assessment of the optic nerve sheath diameter (ONSD) is a useful technique in detecting raised intracranial pressure (ICP) in neurocritical care patients. Its utility in idiopathic intracranial hypertension (IIH) is less known. The aim of this study was to evaluate the diagnostic accuracy of ONSD for detecting IIH. MATERIAL AND METHODS: Ultrasound measurement of ONSD was performed in 19 patients with IIH and in 11 patients with different neurological diseases without raised ICP that required undergoing a lumbar puncture. The validity of this technique for diagnosing IIH was established with cerebrospinal fluid manometry values. RESULTS: Patients with IIH showed significantly enlarged ONSD than those without IIH. The best cut-off point for detecting raised ICP was 6.3 mms, with a sensitivity, specificity and positive likelihood ratio of 94.7%, 90.9% and 10.4, respectively. After a therapeutic lumbar puncture an 87% of cases had a partial reduction of ONSD values. CONCLUSION: Sonographic assessment of ONSD seems to be a useful and reliable technique for detecting raised ICP. While the spinal manometry is not replaced in usual clinical settings, transorbital sonography alternatively allows a suitable and harmless screening of patients with suspected IIH. It would be desirable to perform an internal validation of the technique in each hospital in order to get the optimal cut-off point. PMID- 26810529 TI - Relative preservation of finger flexion in amyotrophic lateral sclerosis. AB - A characteristic pattern of intrinsic hand muscle involvement--known as the split hand sign--is typical of ALS; differential involvement of forearm muscles has not been examined systematically. After observing that finger-flexion was often preserved in ALS, despite severe weakness of finger-extension, we assessed the relative involvement of these two muscle groups in a cohort of patients with ALS. We found finger-flexion to be relatively preserved, when compared with finger extension, in patients with ALS. In many cases finger-flexion is only minimally affected, even when finger-extension is totally paralyzed. The reasons for this predilection are unclear, but may be similar to those underlying the split-hand sign. Nevertheless, the discrepancy may provide another useful clinical clue in patients presenting with distal upper-limb weakness. PMID- 26810530 TI - Hemiparetic Guillain-Barre syndrome. PMID- 26810531 TI - Preoperative motor strength and time to surgery are the most important predictors of improvement in foot drop due to degenerative lumbar disease. AB - OBJECTIVE: Palsy of dorsiflexion, or foot drop, may be due to degenerative lumbar disease and amenable to posterior spinal decompression. The objective of this study is to measure prognostic factors of and time to foot drop improvement after posterior lumbar decompression. METHODS: We retrospectively reviewed 71 patients undergoing first-time, posterior lumbar decompression for foot drop due to degenerative spinal disease. Patient sex, age, comorbidities (Charlson Comorbidity Index), preoperative anterior tibialis strength (manual muscle testing, MMT), and duration of foot drop were ascertained from clinical notes. Prognostic factors affecting foot drop improvement were calculated with a discrete time proportional hazards model, in which follow-up times and outcome measures were binned into six time intervals: 1 week, 6 weeks, 3 months, 6 months, 1 year, and >= 1 year. RESULTS: Of the 71 patients, the mean age was 54.6 +/- 16.0 years, and 66.2% (n=47) were males. The mean Charlson Comorbidity Index was 2.42. During a mean follow-up of 30.4 months, dorsiflexion function improved postoperatively in 73.2% (n=52) of patients. The median time to surgery from onset of foot drop was within 6 weeks, and the median preoperative MMT strength of patients with foot drop improvement was 3. Following a discrete-time proportional hazards model, duration of anterior tibialis palsy (HR=0.67, P=0.004) and preoperative muscle strength (HR=1.10, P=0.010) were significant predictors of foot drop improvement. Following an adjusted Kaplan-Meier analysis, the median time to foot drop improvement was within 6 weeks of surgical intervention. CONCLUSIONS: Preoperative muscle strength and palsy duration were statistically significant predictors of foot drop improvement. Furthermore, the median time to improvement was 6 weeks. PMID- 26810532 TI - Cognitive and neuropsychiatric features of orthostatic tremor: A case-control comparison. AB - INTRODUCTION: Evidence suggests that the cerebellum could play a role in the pathophysiology of orthostatic tremor. The link between orthostatic tremor and the cerebellum is of interest, especially in light of the role the cerebellum plays in cognition, and it raises the possibility that orthostatic tremor patients could have cognitive deficits consistent with cerebellar dysfunction. Our aim was to examine whether orthostatic tremor patients had cognitive deficits and distinct personality profiles when compared with matched controls. METHODS: Sixteen consecutive orthostatic tremor patients (65.7 +/- 13.3 years) and 32 healthy matched controls underwent a neuropsychological battery and the Personality Assessment Inventory. In linear regression models, the dependent variable was each one of the neuropsychological test scores or the Personality Assessment Inventory subscales and the independent variable was orthostatic tremor vs. RESULTS: Adjusted for age in years, sex, years of education, comorbidity index, current smoker, and depressive symptoms, diagnosis (orthostatic tremor vs. healthy control) was associated with poor performance on tests of executive function, visuospatial ability, verbal memory, visual memory, and language tests, and on a number of the Personality Assessment Inventory subscales (somatic concerns, anxiety related disorders, depression, and antisocial features). Older-onset OT (>60 years) patients had poorer scores on cognitive and personality testing compared with their younger-onset OT counterparts. CONCLUSION: Orthostatic tremor patients have deficits in specific aspects of neuropsychological functioning, particularly those thought to rely on the integrity of the prefrontal cortex, which suggests involvement of frontocerebellar circuits. Cognitive impairment and personality disturbances could be disease-associated nonmotor manifestations of orthostatic tremor. PMID- 26810533 TI - Increased plasma UCH-L1 after aneurysmal subarachnoid hemorrhage is associated with unfavorable neurological outcome. AB - OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) is a common cause of long term disability and death. After primary hemorrhage, secondary brain injury is the main cause of mortality and morbidity. Despite extensive research, reliable prognostic biomarkers are lacking. We measured ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) levels in aSAH patients to evaluate its prognostic potential. This is the first time that plasma UCH-L1 has been studied as a potential prognostic biomarker in patients with aSAH. METHODS: In this prospective population-based study, UCH-L1 levels were measured in aSAH patients (n=47) for up to five days. UCH-L1 was measured at 0, 12 and 24h after the admission to the intensive care unit (ICU) and daily thereafter until the patient was transferred from the ICU. Only patients whose UCH-L1 was measured within 24h from aSAH were included in the study. The patients' neurological outcome was evaluated with the modified Rankin Scale (mRS) at six months after aSAH. RESULTS: UCH-L1 levels during the first 24h after aSAH were not significantly different between the groups with favorable (mRS 0-2) and unfavorable (mRS 3-6) neurological outcome. In 22 patients, UCH-L1 levels were obtained for up to five days. In this subgroup, UCH-L1 measured at day five showed significant elevation from baseline levels in patients with unfavorable outcome (p=0.026). Elevated UCH L1 levels at day five were higher in patients with unfavorable outcome than in patients with favorable outcome (p=0.001). CONCLUSIONS: Elevated UCH-L1 levels during the five-day follow-up were associated with unfavorable neurological outcome. Repetitive measurements of UCH-L1 concentrations with an emphasis on change relative to the individual baseline could be the optimal approach for future clinical studies. PMID- 26810534 TI - Initial research on the relationship between let-7 family members in the serum and massive cerebral infarction. AB - Eighty-eight ischemic stroke patients with massive cerebral infarction (MCI) who met our selection criteria were included in this study. MCI was assessed using the Glasgow Coma Scale (GCS) at hospital admission and at 2 weeks. The sera of all patients and controls were sampled at 48 h after the patients' attacks, and the sera of patients with MCI who had no severe cardiopulmonary complications, including those with hemorrhagic transformation (HT), were sampled again at 2 weeks. The relative expression of let-7 miRNA in the serum was determined by real time qRT-PCR, and the blood levels of lipids, glucose, high-sensitivity C reactive protein (hs-CRP), homocysteine and blood pressure were measured at admission. Interleukin-6 (IL-6) levels were detected by ELISA, and a luciferase assay was performed to confirm that IL-6 was a gene target of let-7. The relative expression of let-7f was significantly down-regulated in MCI without HT patients compared with controls (P<0.001), and it was positively correlated with GCS (P<0.01) and negatively correlated with hs-CRP (P<0.01). The relative expression of let-7f was significantly up-regulated in MCI patients with HT (P<0.01). IL-6 is a direct target gene for let-7f, and IL-6 expression was increased in MCI without HT patients compared to controls (P<0.01). The expression of let-7f in serum is associated with MCI without HT, which specifically inhibits IL-6. This suggests that let-7f may control inflammation in patients with MCI without HT. PMID- 26810535 TI - Short-term suboptimal response criteria for predicting long-term non-response to first-line disease modifying therapies in multiple sclerosis: A systematic review and meta-analysis. AB - INTRODUCTION: There is no consensus about short-term suboptimal response to first line treatments in relapsing-remitting multiple sclerosis. METHODS: We searched studies with interferon beta or glatiramer acetate in which a long-term (>= 2 years (y)) outcome could be predicted using short-term (<= 1 y) suboptimal response criteria (EDSS-, imaging- and/or relapse-based). We obtained pooled diagnostic accuracy parameters for the 1-y criteria used to predict disability progression between 2-5 y. RESULTS: We selected 45 articles. Eight studies allowed calculating pooled estimates of 16 criteria. The three criteria with best accuracy were: new or enlarging T2-weighted lesions (newT2) >= 1 (pooled sensitivity: 85.5%; specificity:70.2%; positive predictive value:48.0%; negative predictive value:93.8%), newT2 >= 2 (62.4%, 83.6%, 55.0% and 87.3%, respectively) and RIO score >= 2 (55.8%, 84.4%, 47.8% and 88.2%). Pooled percentages of suboptimal responders were 43.3%, 27.6% and 23.7%, respectively. Pooled diagnostic odds ratios were 14.6 (95% confidence interval: 1.4-155), 9.2 (1.4 59.0) and 8.2 (3.5-19.2). CONCLUSIONS: All criteria had a limited predictive value. RIO score >= 2 at 1-y combined fair accuracy and consistency, limiting the probability of disability progression in the next years to 1 in 8 optimal responders. NewT2 >= 1 at 1-y had similar positive predictive value, but diminished the false negatives to 1 in 16 patients. More sensitive measures of treatment failure at short term are needed. PMID- 26810537 TI - C9ORF72 repeat expansion is not detected in sporadic ataxia patients in mainland China. AB - Expansion of a GGGGCC hexanucleotide repeat in the gene C9ORF72 is a common pathogenic mutation in families with autosomal dominant frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). In order to understand whether pathogenic GGGGCC expansions of C9ORF72 are associated with spinocerebellar ataxia (SCA) in mainland China, we performed an experiment to determine the prevalence of pathogenic hexanucleotide expansions of C9ORF72 in a large cohort of Chinese Han patients with SCA. 411 sporadic patients with SCA and 314 healthy controls were screened for pathogenic hexanucleotide expansions of C9ORF72 utilizing a repeat primed polymerase chain reaction assay. However, no pathological repeat expansion of C9ORF72 was detected in either patients or controls. We therefore conclude that an expansion in C9ORF72 may not play a significant role in SCA in our cohort. However, more studies are needed to draw conclusions for the general population. PMID- 26810536 TI - Manual therapy as an effective treatment for fibrosis in a rat model of upper extremity overuse injury. AB - Key clinical features of carpal tunnel syndrome and other types of cumulative trauma disorders of the hand and wrist include pain and functional disabilities. Mechanistic details remain under investigation but may involve tissue inflammation and/or fibrosis. We examined the effectiveness of modeled manual therapy (MMT) as a treatment for sensorimotor behavior declines and increased fibrogenic processes occurring in forearm tissues of rats performing a high repetition high force (HRHF) reaching and grasping task for 12 weeks. Young adult, female rats were examined: food restricted control rats (FRC, n=12); rats that were trained for 6 weeks before performing the HRHF task for 12 weeks with no treatment (HRHF-CON, n=11); and HRHF task rats received modeled manual therapy (HRHF-MMT, n=5) for 5 days/week for the duration of the 12-week of task. Rats receiving the MMT expressed fewer discomfort-related behaviors, and performed progressively better in the HRHF task. Grip strength, while decreased after training, improved following MMT. Fibrotic nerve and connective tissue changes (increased collagen and TGF-beta1 deposition) present in 12-week HRHF-CON rats were significantly decreased in 12-week HRHF-MMT rats. These observations support the investigation of manual therapy as a preventative for repetitive motion disorders. PMID- 26810538 TI - Dynamic pattern of clinical and MRI findings in a tumefactive demyelinating lesion: A case report. PMID- 26810539 TI - Identifying a therapeutic window in acute and subacute inflammatory sensory neuronopathies. AB - BACKGROUND: Patients with inflammatory sensory neuronopathy (SNN) may benefit from immunomodulatory or immunosuppressant treatments if administered timely. Knowing the temporal profile of neuronal loss in dorsal root ganglia will help to ascertain whether a final diagnosis may be reached before the occurrence of irreversible neuronal injuries. Thus, we addressed the evolution of neuronal loss in SNN by using sensory nerve action potentials (SNAPs) as a surrogate marker of neuron degeneration. METHODS: Eighty-six patients with acute/subacute inflammatory SNN (paraneoplastic, associated with dysimmune diseases, or idiopathic) were retrospectively studied. The monthly SNAP reduction was determined and normalized with the lower limit of normal. Disability progression was expressed by the modified Rankin score and correlated with SNAP reduction. RESULTS: The monthly SNAP reduction was similar in the four limbs although the median nerve was less severely affected. The monthly SNAP reduction was very severe within the first two months of evolution, began to slow down after seven months, and stabilized after ten months. It was tightly correlated with disability progression. Kaplan-Meier analysis showed that the median time until matching the diagnostic criteria of SNN was 8.5 months. Within this period, 42% of nerves remained excitable. CONCLUSIONS: Developing treatment aiming at the stabilization of SNN is possible within the first 8 months of evolution. An improvement of the disease is possible if patients are treated within two months, which needs an early referral to an expert center and ENMG testing of the radial and ulnar nerves, which are most sensitive to changes. PMID- 26810541 TI - Editor's update and selected articles from the Journal of the Neurological Sciences. PMID- 26810540 TI - Lower urinary tract dysfunction in patients with functional movement disorders. AB - INTRODUCTION: Functional movement disorders (FMD) are not associated with the kind of structural or biochemical alterations seen in other movement disorders and therefore would be unlikely to be associated with lower urinary tract (LUT) dysfunction. However, LUT symptoms have been observed in patients with FMD. OBJECTIVE: To evaluate the frequency and pattern of LUT symptoms, their possible nature and the impact they have on the quality of life of patients with FMD. METHODS: The clinical records of patients with FMD were reviewed retrospectively and patients reporting LUT symptoms were invited to complete standardised validated questionnaires-Urinary Symptom Profile (USP) and Short Form-Qualiveen (SFQ). Management of LUT dysfunction was also reviewed. RESULTS: Out of the 150 patients with clinically established (n=97) or probable (n=53) FMDs, thirty (20%) self-reported LUT symptoms. Twenty two of these completed the USP and SFQ questionnaires. Overactive bladder symptoms were most commonly reported (n=14; 63.6%). Patients with fixed dystonia reported more severe LUT symptoms and had higher SFQ scores as compared to patients with other FMDs (p=0.01). Five patients with significant LUT symptoms had been referred to uroneurology. Of them, three had urinary retention managed with sacral neuromodulation, two had overactive bladder and were managed conservatively. CONCLUSION: LUT dysfunction can be seen in 20% patients with FMD. Patients with fixed dystonia are more likely to report LUT dysfunction which can be severe. It may be advisable to ask for LUT symptoms in all patients with FMD and be more proactive in referring them for specialist investigation and treatment. PMID- 26810542 TI - Down-regulation of adenosine A1 and A2A receptors in peripheral cells from idiopathic normal-pressure hydrocephalus patients. AB - Idiopathic normal-pressure hydrocephalus (iNPH) is a neurological disease that usually develops in the elderly. Natural history of iNPH is still unknown. It has been hypothesized that cerebrovascular diseases could have a role in etiology of chronic hydrocephalus and studies show an increased prevalence of cardiovascular diseases in iNPH patients. Moreover, evidences show a possible alteration of immune system in iNPH patients. Adenosine (Ado) is a metabolite produced in response to metabolic stress and injury. Adenosine and its receptors play an important role in vascular protection and in the modulation of inflammatory reactions and neuroinflammation. Our aim is to evaluate gene and protein expression of A1R and A2AR in the peripheral blood mononuclear cells (PBMCs) from iNPH patients compared to control subjects. We investigate if Ado system, that plays an important role in central nervous system, in vascular system, and also in inflammation, is involved in pathophysiology of iNPH disease. Our analysis showed that A1R mRNA levels and A1R density in PBMCs from iNPH patients were significantly lower than CT subjects (0.84 +/- 0.12 and 2.42 +/- 0.42, p<0.001 and 0.31 +/- 0.02 and 0.42 +/- 0.04, p=0.043; respectively). About A2AR, the gene expression in PBMCs was significantly lower in iNPH than CT (0.65 +/- 0.09 and 1.5 +/- 0.14, p<0.001) as well as there was a trend in protein expression: iNPH and CT (0.51 +/- 0.05 and 0.62 +/- 0.03; p=0.172). This preliminary study underlines the involvement of Ado system in iNPH disease whose pathophysiology is still unclear. PMID- 26810543 TI - The association of pathological laughing and crying and cognitive impairment in multiple sclerosis. AB - BACKGROUND: Pathological laughing and crying (PLC) is common in multiple sclerosis (MS), defined as emotional expression that is exaggerated/incongruent with underlying mood. In other neurological disorders, PLC is associated with cognitive impairment (CI). Few studies have examined this relationship in MS. OBJECTIVE: To determine the association between PLC and CI in an MS population. METHODS: Retrospective chart review study of 153 MS subjects assessed in an outpatient clinic for CI. Data was collected on the minimal assessment of cognitive function in MS (MACFIMS), the Center for neurological study-lability scale (CNS-LS), a screening measure for PLC symptoms and the hospital anxiety and depression scale (HADS). Analyses of covariance compared performance on the MACFIMS between PLC (CNS-LS score >= 17, HADS-D <= 7) and non-PLC groups. RESULTS: MS subjects positive for PLC on the CNS-LS but without depression had lower scores on the controlled oral word association test, a measure of verbal fluency, and the California verbal learning test - 2 immediate recall score, a verbal memory measure. CONCLUSIONS: This study demonstrates a connection between CI, specifically verbal fluency and verbal learning, and PLC in MS subjects. Further studies are warranted to explore the causative relationship between CI and PLC. PMID- 26810544 TI - Neuromyelitis optica spectrum initially diagnosed as antiphospholipid antibody myelitis. PMID- 26810545 TI - Effect of lumbo-peritoneal shunt surgery on neuropsychiatric symptoms in patients with idiopathic normal pressure hydrocephalus. AB - INTRODUCTION: Patients with idiopathic normal pressure hydrocephalus (iNPH) have neuropsychiatric symptoms that could affect patients' quality of life and caregiver burden. In this study, we assessed the effect of lumbo-peritoneal (L-P) shunt surgery on neuropsychiatric symptoms and the association between neuropsychiatric symptoms and caregiver burden after L-P shunt surgery. METHODS: We recruited 22 iNPH patients who had L-P shunt surgery and who were followed up for 3 months after surgery. Neuropsychiatric symptoms and caregiver burden were evaluated with the Neuropsychiatric Inventory (NPI) and Zarit Burden Interview (ZBI), respectively, before and 3 months after surgery. We evaluated the changes of NPI and ZBI and the association between the changes in these 2 scores and the triad symptoms. RESULTS: NPI total, apathy, and depression scores significantly decreased after surgery. The improvement in NPI total, apathy, disinhibition, and irritability scores after surgery were significantly and positively associated with improvement in ZBI score after surgery. Improvement in NPI apathy score was significantly associated with improvement in Frontal Assessment Battery score after surgery. CONCLUSION: L-P shunt surgery was effective in reducing not only the triad symptoms but also the neuropsychiatric symptoms, and the improved neuropsychiatric symptoms might decrease caregiver burden for iNPH patients. PMID- 26810546 TI - Epstein-Barr virus and multiple sclerosis. From evidence to therapeutic strategies. AB - Multiple sclerosis is caused by a complex interaction between genetic predisposition and environmental factors. Epstein-Barr virus (EBV) is an environmental risk factor that is strongly related to multiple sclerosis (MS), since EBV seropositivity is linked to a significant risk of developing MS. EBV may be involved in the pathogenesis of the disease and it is possibly a prerequisite for the development of MS. EBV infection persists in B-cells during the lifetime of the host and can modulate their function. In addition, MS patients might have a deficient capacity to eliminate latent EBV infection in the central nervous system and this would promote the accumulation of infected B cells. Several mechanisms of pathogenesis, including a direct and indirect function of infected B cells, have been postulated in inflammation and neurodegeneration. A relationship between EBV and human endogenous retroviruses in the pathogenesis of MS has also been reported. If EBV is important in the pathogenesis of MS, different therapeutic strategies seem possible for MS treatment. PMID- 26810547 TI - BECLA, a new assessment battery for acquired deficits of language: Normative data from Quebec-French healthy younger and older adults. AB - Compared to English, for which there exist numerous tests and batteries for the assessment of acquired deficits of language, the tools available to assess French speaking individuals are much more limited. The Batterie d'Evaluation Cognitive du Langage (BECLA) was purposely developed to fulfill the need for French assessment tools based on theoretical models of cognitive psychology. It comprises 19 tasks, designed to assess each of the components and routes involved in single word processing in order to identify the functional locus/loci of impairment. In this article, we describe the BECLA and we present normative data for individuals 18-94 years of age (N=248). The sample was stratified by age, gender, and years of education, according to the Institut de la statistique du Quebec, in order to be representative of the French-Quebec population. Percentile scores were provided for each BECLA task in order to show the relative rank of each raw score according to significant correlates. The BECLA is a new clinical, theoretically based assessment battery, useful for identifying and characterizing acquired deficits of language in younger and older adults. PMID- 26810548 TI - Effects of soybean ingestion on pharmacokinetics of levodopa and motor symptoms of Parkinson's disease--In relation to the effects of Mucuna pruriens. AB - Mucuna pruriens is a levodopa-containing legume and its favorable effects on motor complications in Parkinson disease patients have been reported. The aim of this study was to investigate the effects of another legume, soybeans, on the pharmacokinetics and metabolism of levodopa. Seven parkinsonian patients with the wearing-off phenomenon and dyskinesia and five healthy volunteers participated in this study. We conducted a crossover study of the clinical effects on the participants before and after taking either levodopa (100mg)/carbidopa (10mg) only (LD/CD) or levodopa/carbidopa with 11 g of ground soybeans (LD/CD/soy). Parkinsonism and dyskinesia before and after ingestion of these substances were evaluated using UPDRS part III, the modified Abnormal Involuntary Movement Scale (mAIMS) and a self-rating scale. The concentrations of plasma levodopa and its major metabolites were measured by high-performance liquid chromatography. Clinical assessment and blood sampling were conducted before and three hours after the ingestion of ground soybeans. When the patients took LD/CD/soy, they had a significantly longer on-period (p=0.028) and a lower mAIMS score (p<0.001). From the comparison of the results of pharmacokinetic study before and after taking LD/CD or LD/CD/soy, the estimated marginal mean (EMM) of HVA after LD/CD/soy increased in the PD group. EMMs of 3-OMD after LD/CD/soy significantly decreased both in PD patients and healthy controls. These results indicate that soy partly increased the bioavailability of levodopa and suppressed levodopa degradation through COMT. Soybeans may have favorable effects on the motor complications occurring under current levodopa therapy. Further investigation to clarify the mechanism underlying such effects is required. PMID- 26810549 TI - Coping with amyotrophic lateral sclerosis; from diagnosis and during disease progression. AB - To evaluate coping strategies among patients with Amyotrophic lateral sclerosis starting with diagnosis and during the disease progression, as well as investigate changes and correlations between coping strategies, emotional well being and physical function. A total of 36 patients participated in the study. The patients filled out the Hospital Anxiety and Depression Scale and the Motor Neuron Disease Coping Scale. Physical function was measured using the revised ALS functional rating scale. Data were collected regularly from diagnosis and over a two years period. As a way to cope with the disease patients relied on both problem focused and emotional focused strategies. The use of coping strategies remained stable. Both physical disabilities and emotional well-being was related to some coping strategies, with some variation during the disease progression. Moreover, some coping strategies were related to symptoms of anxiety and depression. Irrespective of whether the coping strategies affect the emotional well-being or vice versa, the results show the importance of early and continuous evaluation of coping and emotional well-being to ease the emotional distress and provide support to the patient so that he/she can cope with the disease during the disease progression. PMID- 26810550 TI - Laryngeal stridor in multiple system atrophy: Clinicopathological features and causal hypotheses. AB - Laryngeal stridor is recognized as a characteristic clinical manifestation in patients with multiple system atrophy (MSA). However, the pathogenic mechanisms underlying this symptom are controversial. Neurogenic atrophy of the posterior cricoarytenoid muscle has been identified in cases of MSA, suggesting that laryngeal abductor weakness contributes to laryngeal stridor. However, dystonia in the laryngeal adductor muscles has also been reported to cause laryngeal stridor. Depletion of serotonergic neurons in the medullary raphe nuclei, which exert tonic drive to activate the posterior cricoarytenoid muscle, has recently been identified in MSA cases. This adds weight to the possibility that laryngeal abductor weakness underlies laryngeal stridor in MSA. Continuous positive airway pressure therapy is currently used in the treatment of laryngeal stridor, but should be used with caution in patients showing contraindications. Current knowledge of the clinical and neuropathological features of laryngeal stridor is summarized in this paper, and the hypothesized causes and possible therapeutic options for this symptom are discussed. PMID- 26810551 TI - Association between polymorphism of COMT gene (Val158Met) with Alzheimer's disease: An updated analysis. AB - Previous studies have proposed the association between catechol-o methyltransferase (COMT) Val158Met polymorphism and the risk of Alzheimer's disease (AD). However, there has been no solid conclusion from those reports because of the limited sample size and/or racial diversity. Here we aimed to give an in-depth and accurate evaluation of this association by performing a comprehensive literature search on websites including PubMed, EMBASE, Alzgene database, Cochrane library and Ovid database. In further meta-analysis we identified 10 case-control studies which contained total 2777 cases and 2829 controls. Summarized odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were assessed to reveal the association. There was no significant association between COMT Val158Met polymorphism and AD susceptibility in all genetic models for the entire population. In the contrast the subgroup analysis stratified by ethnicity revealed significant differences in the Asian population in the dominant (OR=0.66, 95%CI=0.50, 0.87, p=0.004); homozygous (OR=0.66, 95%CI=0.50, 0.89, p=0.006); and heterozygous models (OR=0.65, 95%CI=0.48, 0.87, p=0.004). However, no association was found in the Caucasians population. Similarly to the overall analysis, subgroup analysis of the control population stratified with HWE showed negative results. With the latest comprehensive searching strategy, our updated meta-analysis suggested that COMT Val158Met polymorphism could decrease the risk of AD in the Asian population, but not in the Caucasian or the overall population. PMID- 26810552 TI - Alzheimer's disease: An overview of amyloid beta dependent pathogenesis and its therapeutic implications along with in silico approaches emphasizing the role of natural products. AB - Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by amyloid beta (Abeta) deposition in brain with subsequent formation of neuritic plaques leading to dementia. A number of therapeutic strategies targeted against Abeta depositions have been rigorously explored which provided successful results corresponding to the existing symptomatic treatments. However, at the same time, several failures corresponding to the disease altering therapies and drugs have also been observed due to potential drawbacks in understanding of the pathogenesis of the disease, development of drug candidates and subsequent designing of clinical trials. Preclinical research, along with experimental and clinical studies, is continuously providing novel information which may reveal multi-target directed ligands and combination therapies for targeting Abeta. Thus, in view of the estimated increase in the number of AD patients globally, the present review attempts to summarize the available evidence dealing with various therapeutic approaches targeting Abeta, focusing specifically on pharmaceutical compounds under various stages of clinical trials. Furthermore, in view of a number of computational advances having significant impact in the field of computer aided drug design, we have also presented results of analysis of natural compounds as potential therapeutic molecules in preventing Abeta plaque formation using in silico approaches. PMID- 26810554 TI - Sparing of the nipple-areola complex in segmental dermal melanocytosis involving the breast. PMID- 26810553 TI - Medically unexplained visual loss in a specialist clinic: a retrospective case control comparison. AB - PURPOSE: To compare the clinical and demographic characteristics of adult patients with nonorganic or medically unexplained visual loss (MUVL) to those with other common conditions presenting to a neuro-ophthalmology clinic. METHODS: Case-control design: a retrospective review of medical notes on a consecutive case series of 49 patients assessed at the King's College Hospital neuro ophthalmology clinic with unexplained visual loss and matched with the next assessed patient identified from clinic records. Patients presented post-symptom onset with a mean clinical course of 30 months (SD=67 months) and standard clinical examination used to confirm diagnoses, alongside ancillary investigations if required. RESULTS: Seventy-two percent (n=36) of MUVL patients were female. In comparison with patients with organic visual disorders, MUVL cases presented with significantly higher rates of bilateral (cf. unilateral) visual impairment (41%, n=20), premorbid psychiatric (27%, n=13) as well as functional (24%, n=12) diagnoses and psychotropic medication usage (22%, n=11). Medically unexplained cases were significantly more likely to report preceding psychological stress (n=9; 18%). CONCLUSIONS: Medically unexplained visual impairment may be regarded as part of the spectrum of medically unexplained disorders seen in the general hospital setting. Research is needed to determine long-term outcomes and effective tailored interventions. PMID- 26810557 TI - Response to: "Indicators of health system coverage and activity in Ireland during the economic crisis 2008-2014--From 'more with less' to 'less with less"'. PMID- 26810556 TI - Timing Matters - Influenza Vaccination to HIV-Infected Patients. AB - OBJECTIVES: Patients with HIV infection vaccinated early in the flu season are more likely to contract influenza or influenza-like illness (ILI) compared with those receiving late vaccination. It is known that antibody titres wane over time, particularly among individuals with HIV infection. It is unclear if the timing of influenza vaccination within the flu season affects the probability of an influenza infection later during the flu season. The aim of this study is to evaluate if there is a relationship between the timing of influenza vaccination and incidence of influenza or ILI in patients with HIV infection. METHODS: A retrospective cohort study of HIV-infected patients in care at the Department of Veterans Affairs San Diego Healthcare System was conducted from 1 September 2005 to 31 May 2013. Among these patients, we evaluated whether there was a relationship between the timing of influenza vaccination and the incidence of laboratory-confirmed influenza, influenza diagnosed by a physician, or ILI. RESULTS: Patients who received influenza vaccine early in the season were more likely to contract influenza or ILI than patients who were vaccinated late (P < 0.01). Vaccinated patients who developed influenza or ILI were more likely to do so later in the season (P < 0.01). CONCLUSIONS: HIV-infected patients vaccinated early in the flu season were more likely to contract influenza or ILI than those vaccinated later in the season. PMID- 26810561 TI - Flagellar Sensillar Equipment of Two Morphologically Closely Related Aphid Hyperparasitoids (Hymenoptera: Figitidae: Alloxysta). AB - The antennal sensillar equipment in the parasitic wasp family Figitidae was analyzed to date only in few species, despite some are associated with crop pests and can have an economic importance. It is the case of the genus Alloxysta, which includes hyperparasitoids of aphids which can potentially reduce effectiveness of primary pest parasitoids. Here we analyzed, through scanning electron microscopy, the diversity, morphology, and distribution of the antennal sensilla in males and females of Alloxysta consobrina (Zetterstedt) and Alloxysta victrix (Westwood), two species with overall very similar morphology. In both species, antennae are filiform and cylindrical, and flagellum was longer in A. victrix. Eight sensillar types have been recognized: four types of sensilla trichoidea (ST-A, ST-B, ST-C, ST-D), sensilla coeloconica, sensilla placoidea, sensilla campaniformia, and sensilla basiconica. ST-A, ST-B, ST-C, and sensilla placoidea were the most abundant types on the antennae and often increased in number and decreased in size toward the tip of antenna. The two species seem to have several differences in their sensillar equipment, possibly in accordance with the different degree of host range. On the other hand, sexual dimorphism is probably due to the different stimuli that have to be correctly processed. The comparison with the other species of Figitidae studied by far showed, at subfamily-level, that variability in sensillar equipment and phylogeny do not agree. This suggests a complex series of morphological changes during evolution of this group. The taxonomic sample should be thus substantially enlarged to disclose possible trends in sensillar equipment evolution in the family. PMID- 26810560 TI - The Complete Mitochondrial Genome of Brachmia macroscopa (Lepidoptera: Gelechiidae) and Its Related Phylogenetic Analysis. AB - The sweet potato leaf folder, Brachmia macroscopa, is an important pest in China. The complete mitogenome, which consists of 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes, and an A + T-rich region, was sequenced and found to be 15,394 bp in length (GeneBank no. KT354968). The gene order and orientation of the B. macroscopa mitogenome were similar to those of other sequenced lepidopteran species. All of the PCGs started with ATN as the canonical start codon except for cox1, which started with CGA. In regard to stop codons, most PCGs stopped at TAA except for cox2, which stopped at TA, and nad4, which stopped at a single T. Thirteen PCGs of the available species (33 taxa) were used to demonstrate phylogenetic relationships. The ditrysian cluster was supported as a monophyletic clade at high levels by using maximum likelihood and Bayesian methods. The apoditrysian group, covering the Gelechioidea, formed a monophyletic clade with a bootstrap value of 88% and a posterior probability of 1.00. The superfamily Gelechioidea was supported as a monophyletic lineage by a posterior probability of 1.00. PMID- 26810562 TI - Helicopter-based emergency medical services for a sparsely populated region: A study of 42,500 dispatches. AB - BACKGROUND: The Helicopter Emergency Medical Service (HEMS) in Norway is operated day and night, despite challenging geography and weather. In Western Norway, three ambulance helicopters, with a rapid response car as an alternative, cover close to 1 million inhabitants in an area of 45,000 km(2) . Our objective was to assess patterns of emergency medical problems and treatments in HEMS in a geographically large, but sparsely populated region. METHODS: Data from all HEMS dispatches during 2004-2013 were assessed retrospectively. Information was analyzed with respect to patient treatment and characteristics, in addition to variations in services use during the day, week, and seasons. RESULTS: A total of 42,456 dispatches were analyzed. One third of the patients encountered were severely ill or injured, and two thirds of these received advanced treatment. Median activation time and on-scene time in primary helicopter missions were 5 and 11 min, respectively. Most patients (95%) were reached within 45 min by helicopter or rapid response car. Patterns of use did not change. More than one third of all dispatches were declined or aborted, mostly due to no longer medical indication, bad weather conditions, or competing missions. CONCLUSION: One third of the patients encountered were severely ill or injured, and more than two thirds of these received advanced treatment. HEMS use did not change over the 10 year period, however HEMS use peaked during daytime, weekends, and the summer. More than one third of all dispatches were declined or aborted. PMID- 26810563 TI - Outcome of rectal cancer surgery in obese and nonobese patients: a meta-analysis. AB - BACKGROUND: The escalating global epidemic of obesity is of worldwide concern because of its association with serious negative effects on health. The technical difficulty of rectal cancer surgery is exacerbated in obese patients, which may compromise outcomes. High-quality, relevant evidence is limited. This meta analysis aims to assess the outcomes of rectal cancer surgery in obese and nonobese patients. METHODS: The electronic databases Pubmed, Medline, Embase, Web of Science, and the Cochrane Library were used to search for articles that evaluated the outcomes of rectal cancer surgery in obese and nonobese patients. Fixed-effects and random-effects models were used to calculate the combined overall effect sizes of pooled data. Data are presented as odds ratios (OR) or weighted mean differences (WMD) with 95% confidence intervals (CIs). RESULTS: Ten appropriate observational studies were identified from 290 published articles. In the obese group, conversion rates (OR 2.78; 95% CI 1.67-4.61), overall morbidity (OR 1.36; 95% CI 1.25-1.47), anastomotic leak (OR 3.94; 95% CI 1.88-8.24), wound infection (OR 2.22; 95% CI 1.47, 3.36), and pulmonary events (OR 2.10; 95% CI 1.18, 3.74) were all significantly increased. For pathological results, no statistical differences in the number of harvested lymph nodes and the positive margin were noted between the two groups. CONCLUSIONS: Based on a meta-analysis, obesity increases the conversion rate and postoperative morbidity of rectal cancer surgery but does not influence pathological results. PMID- 26810564 TI - Cognitive Function in Older Suicide Attempters and a Population-Based Comparison Group. AB - OBJECTIVE: The aim was to compare cognitive function in older suicide attempters with a population-based comparison group. METHODS: Hospitalized suicide attempters aged 70 years and older were assessed cognitively at baseline (n = 99) and 1-year follow-up (n = 59). Depression symptoms were rated with the Montgomery Asberg Depression Rating Scale (MADRS). Results of cognitive assessments in attempters were compared with results in nonattempter comparison subjects (n = 115) selected among participants in our population-based health studies to yield a similar distribution of MADRS scores. RESULTS: Suicide attempters scored lower on Mini-Mental State Examination (MMSE) than comparison persons. Among attempters, the mean MMSE score was lower in those with medically serious attempts. Attempters displayed poorer performance on tests of pentagon drawing and abstract thinking compared to comparison persons, and the results remained also after exclusion of those with medically serious attempts. At 1-year follow up, significant improvement in MADRS scores was observed in the attempters. No evidence of improvement could be shown regarding cognitive deficits. CONCLUSION: Older suicide attempters may have cognitive deficits, which may in part be related to the attempt itself. This needs to be taken into account when designing intervention strategies. PMID- 26810565 TI - Incidence of chronic heart failure with preserved left ventricular ejection fraction in patients with hypertension and isolated mild diastolic dysfunction. AB - INTRODUCTION: Heart failure (HF) with preserved ejection fraction (HFPEF) is still a challenge in clinical practice. The prognosis of patients with HFPEF is similar to or only slightly better than that of patients with HF with reduced ejection fraction (HFREF). Impaired relaxation is the mildest form of diastolic dysfunction, which should not be accompanied by symptoms of HFPEF. OBJECTIVES: The aim of the study was to assess the incidence of chronic HFPEF in patients with hypertension and isolated mild diastolic dysfunction. PATIENTS AND METHODS: It was a cross-sectional study including 210 patients (mean age, 56.11 +/-6.24 years; women, 58%) with isolated abnormalities of left ventricular relaxation and arterial hypertension. In addition, we identified patients with type 2 diabetes to compare the incidence of HFPEF between patients with and without diabetes. HFPEF was diagnosed when clinical symptoms of HF were present simultaneously with echocardiographic markers of elevated left ventricular diastolic pressure, pulmonary congestion on chest X-ray, or elevated serum brain natriuretic peptide (BNP) levels. RESULTS: HFPEF was diagnosed in 42% of the patients with impaired relaxation. An elevated left atrial volume index (>34 ml/m2) was observed in 38% of the patients; E/e' ratio exceeding 8, in 37%; elevated BNP levels, in 39%; and pulmonary congestion on chest X-ray, in 41%. Independent predictors of HFPEF were age, systolic blood pressure of 140 mmHg or higher, type 2 diabetes, coronary artery disease, and an estimated glomerular filtration rate of less than 60 ml/min/1.73 m2. In diabetic patients, a positive correlation was found between an insulin dose (>80 units/day) and BNP levels. CONCLUSIONS: Patients with isolated relaxation abnormalities constitute a clinically heterogeneous group because some of these individuals present with symptoms of HFPEF and a simultaneous increase in BNP levels. Therefore, the question of whether diastolic dysfunction is mild should be readdressed, and it should be emphasized that these patients have a serious prognosis with the risk of HF. In diabetic patients, a positive correlation between high insulin doses and BNP levels requires further research. PMID- 26810566 TI - Redefining cancer immunotherapy-optimization, personalization, and new predictive biomarkers: 4th Cancer Immunotherapy and Immunomonitoring (CITIM) meeting, April 27-30, 2015, Ljubljana, Slovenia. PMID- 26810567 TI - Selection and expansion of natural killer cells for NK cell-based immunotherapy. AB - Natural killer (NK) cells have been used in several clinical trials as adaptive immunotherapy. The low numbers of these cells in peripheral blood mononuclear cells (PBMC) have resulted in various approaches to preferentially expand primary NK cells from PBMC. While some clinical trials have used the addition of interleukin 2 (IL-2) to co-stimulate the expansion of purified NK cells from allogeneic donors, recent studies have shown promising results in achieving in vitro expansion of NK cells to large numbers for adoptive immunotherapy. NK cell expansion requires multiple cell signals for survival, proliferation and activation. Thus, expansion strategies have been focused either to substitute these factors using autologous feeder cells or to use genetically modified allogeneic feeder cells. Recent developments in the clinical use of genetically modified NK cell lines with chimeric antigen receptors, the development of expansion protocols for the clinical use of NK cell from human embryonic stem cells and induced pluripotent stem cells are challenging improvements for NK cell based immunotherapy. Transfer of several of these protocols to clinical-grade production of NK cells necessitates adaptation of good manufacturing practice conditions, and the development of freezing conditions to establish NK cell stocks will require some effort and, however, should enhance the therapeutic options of NK cells in clinical medicine. PMID- 26810568 TI - Flavonoid and phenolic acid profile by LC-MS/MS and biological activity of crude extracts from Chenopodium hybridum aerial parts. AB - Extracts from leaves and stems of Chenopodium hybridum were characterised for the presence and quantity of flavonoids and phenolic acids by LC-ESI-MS/MS. Five flavonoids and eight phenolic acids were detected for the first time in aerial parts of this plant species, the most abundant compounds being rutin (2.80 MUg/g DW), 3-kaempferol rutinoside (2.91 MUg/g DW), 4-OH-benzoic (1.86 MUg/g DW) and syringic acids (2.31 MUg/g DW). Extracts were tested for anti inflammatory/antiarthritic, antihyaluronidase and cytotoxic activities against human prostate cancer (Du145, PC3) and melanoma cell lines (A375, HTB140 and WM793) of different malignancy. None of the extracts protected bovine serum albumin from heat-induced denaturation. Antihyaluronidase effect at the tested concentration was higher than standard naringenin. Cytotoxic activity was generally low with an exception of the extract from the leaves, which was found most effective against prostate Du145 cell line with 98.28 +/- 1.13% of dead cells at 100 MUg/mL. PMID- 26810569 TI - New-generation narrow band imaging improves visibility of polyps: a colonoscopy video evaluation study. AB - BACKGROUND: The benefits of narrow band imaging (NBI) in colorectal polyp detection remain questionable. Previous NBI has poorer brightness and resolution than white light (WL). However, recently these factors were improved by the new generation video processor system (EVIS LUCERA ELITE) in comparison with the previous system (EVIS LUCERA SPECTRUM). The aim of this study was to investigate whether NBI with EVIS LUCERA ELITE could improve the visibility of colorectal polyps compared to WL. METHODS: We analyzed prospectively 240 colorectal polyps (group 1: ELITE with CF-HQ290 scope, 80 polyps; group 2: ELITE with PCF-Q260AZI scope, 80 polyps; group 3: SPECTRUM with PCF-Q260AZI scope, 80 polyps) whose videos were recorded using NBI and WL at Kyoto Prefectural University of Medicine. The videos were evaluated in a randomized order by three experts and three non-experts. Each polyp was assigned a polyp visibility score from 4 (excellent visibility) to 1 (poor visibility). The polyp visibility scores in each mode and their relationship to the clinical characteristics were analyzed. RESULTS: The mean polyp visibility scores of NBI with ELITE system were significantly higher than those of WL (ELITE with CF-HQ290: 3.14 +/- 0.87 vs. 2.75 +/- 0.98, p < 0.0001, ELITE with PCF-Q260AZI: 3.03 +/- 0.92 vs. 2.83 +/- 0.93, p = 0.0006). Conversely, the mean polyp visibility score of NBI using SPECTRUM system with PCF-Q260AZI was significantly lower than WL (2.75 +/- 1.06 vs. 3.05 +/- 0.92, p < 0.0001). CONCLUSIONS: Our study showed that NBI using EVIS LUCERA ELITE improved polyp visibility. PMID- 26810570 TI - Ameliorative effects of tannic acid on carbon tetrachloride-induced liver fibrosis in vivo and in vitro. AB - We investigated the ameliorative effects and potential mechanisms of tannic acid (TA) in carbon tetrachloride (CCl4)-intoxicated mice and hepatic stellate cells (HSCs). Liver fibrosis was observed in CCl4 (800 ml/kg)-induced mice, and high viability was observed in CCl4 (10 mM)-intoxicated HSCs. Pre-treatment of mice with TA (25 or 50 g/kg/day) significantly ameliorated hepatic morphology and coefficient values and reduced the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), the concentrations of malondialdehyde (MDA) and serum levels of endothelin-1 (ET-1). In addition, TA increased the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and endothelial nitric oxide synthase (eNOS) and the serum level of NO. Moreover, TA reduced the expression of angiotensin II receptor-1 (ATR-1), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor beta (TGF-beta), caspase-3, c-fos, c-jun, the ratio of Bax/bcl-2, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TA increased matrix metal proteinase-9 (MMP-9), matrix metalloproteinase-1 (MMP-1). Furthermore, TA (0.01 MUM, 0.1 MUM or 1 MUM) decreased the TIMP-1/MMP-1 ratio and reduced the viability of HSCs. These results indicated that TA exerts significant liver-protective effects in mice with CCl4-induced liver fibrosis. The potential mechanism may rely on the inhibition of collagen accumulation, oxidative stress, inflammation and apoptosis. PMID- 26810571 TI - Estrogen receptor-alpha36 is involved in epigallocatechin-3-gallate induced growth inhibition of ER-negative breast cancer stem/progenitor cells. AB - Epigallocatechin-3-gallate (EGCG) is a type of catechin extracted from green tea, which is reported to have anticancer effects. EGCG is also reported to inhibit the cancer stem/progenitor cells in several estrogen receptor (ER)-negative breast cancer cell lines, such as SUM-149, SUM-190 and MDA-MB-231. And all these cancer cells are highly expressed a new variant of ER-alpha, ER-alpha36. The aim of our present study is to determine the role of ER-alpha36 in the growth inhibitory activity of EGCG towards ER-negative breast cancer MDA-MB-231 and MDA MB-436 cells. We found that EGCG potently inhibited the growth of cancer stem/progenitor cells in MDA-MB-231 and MDA-MB-436 cells, and also reduced the expression of ER-alpha36 in these cells. However, in ER-alpha36 knocked-down MDA MB-231 and MDA-MB-436 cells, no significant inhibitory effects of EGCG on cancer stem/progenitor cells were observed. We also found that down-regulation of ER alpha36 expression was in accordance with down-regulation of EGFR, which further verified a loop between ER-alpha36 and EGFR. Thus, our study indicated ER-alpha36 is involved in EGCG's inhibitory effects on ER-negative breast cancer stem/progenitor cells, which supports future preclinical and clinical evaluation of EGCG as a therapeutic option for ER-alpha36 positive breast cancer. PMID- 26810572 TI - Spatial and temporal aspects of visual backward masking in children and young adolescents. AB - The development of visual functions is very diverse. Some visual functions mature within the first year of life, whereas maturation for other functions extends into adolescence. The reasons for these developmental differences are largely unknown. Here, we investigated spatiotemporal processing in children (7-9 years, n = 15), young adolescents (11-13 years, n = 26), and adults (18-33 years, n = 24) using the shine-through visual backward-masking paradigm. We found that children had significantly longer vernier durations than either young adolescents or adults. However, children's spatial and temporal processing of complex masks was very similar to that of young adolescents and adults. We suggest that spatiotemporal processing related to visual backward masking is already fully developed at age 7, whereas the attentional processes related to target enhancement only mature in young adolescence. PMID- 26810573 TI - A common mechanism behind distractor-response and response-effect binding? AB - Short-term bindings between responses and events in the environment ensure efficient behavioral control. This notion holds true for two particular types of binding: bindings between responses and response-irrelevant distractor stimuli that are present at the time of responding, and also for bindings between responses and the effects they cause. Although both types of binding have been extensively studied in the past, little is known about their interrelation. In three experiments, we analyzed both types of binding processes in a distractor response binding design and in a response-effect binding design, which yielded two central findings: (1) Distractor-response binding and response-effect binding effects were observed not only in their native, but also in the corresponding "non-native" design, and (2) a manipulation of retrieval delay affected both types of bindings in a similar way. We suggest that a general and unselective mechanism is responsible for integrating own responses with a large variety of stimuli. PMID- 26810578 TI - Src family kinases suppress differentiation of brown adipocytes and browning of white adipocytes. AB - Brown adipocytes and beige adipocytes can expend energy, generate heat, and increase whole-body energy expenditure. The detailed mechanisms of adipogenesis and thermogenesis of these cells are still obscure. Here, we show that Src family kinases (SFKs) regulate both brown adipogenesis and browning of white adipocytes. To identify factors involved in brown adipogenesis, we first examined the effect of several chemical inhibitors on the differentiation of brown preadipocytes isolated from mouse brown adipose tissue (BAT) and found that treatment with PP2, the specific inhibitor of SFKs, promoted the differentiation. Another inhibitor of SFKs, PP1, also promoted the brown adipogenesis, whereas an inactive analogue of PP2, PP3, did not. Moreover, over-expression of C-terminal Src kinase (CSK), the negative regulator of SFKs, also promoted brown adipogenesis. Next, we examined the effect of inhibition of SFKs on the differentiation of white preadipocytes isolated from white adipose tissue (WAT). Our results showed that either PP2 treatment or CSK-over-expression generated Ucp1-positive beige adipocytes, thus inducing browning of white adipocytes. Finally, our analysis showed that the expression levels and activity of SFKs in WAT were much higher than in BAT. These results taken together suggest that SFKs regulate differentiation and browning of fat cells in vivo. PMID- 26810576 TI - Age-related effects of job characteristics on burnout and work engagement. AB - BACKGROUND: In light of an ageing and age-diverse workforce, it is imperative to understand how psychosocial aspects of work might influence health throughout working life. Recently, there has been an implicit call to differentiate job characteristics beyond the two factors of job demands and job resources. As needs, abilities and motivation fluctuate with age, different job characteristics might yield differential benefits. Additionally, markers beyond chronological age should be considered. AIMS: To explore systematically interactions between different job characteristics, age and age covariates (i.e. job tenure and position type) and their relationship with work-related health outcomes. METHODS: An online survey of workers in Switzerland, Austria and Germany, recruited through a panel data service provider. We excluded participants working fewer than 30 hours a week, trainees, self-employed people and senior managers. We assessed seven areas of psychosocial risks at work, burnout, work engagement and demographics. RESULTS: Of the 6000 workers contacted, 1916 responded (31%). After applying exclusion criteria, we analysed data from 1417 respondents. We found that age barely had a moderating effect between psychosocial factors and health outcomes, but its three-way interaction with age covariates had more explanatory potential. Young workers with high job tenure showed particular vulnerability to job demands and the lack of certain job resources. Older workers with managerial positions were more resilient. CONCLUSIONS: Age and its covariates, such as job tenure and position type, should be considered in developing age-sensitive occupational health models. PMID- 26810575 TI - Caregiving Practice Patterns of Asian, Hispanic, and Non-Hispanic White American Family Caregivers of Older Adults Across Generations. AB - This study is a cross-sectional investigation of caregiving practice patterns among Asian, Hispanic and non-Hispanic White American family caregivers of older adults across three immigrant generations. The 2009 California Health Interview Survey (CHIS) dataset was used, and 591 Asian, 989 Hispanic and 6537 non-Hispanic White American caregivers of older adults were selected. First, descriptive analyses of caregivers' characteristics, caregiving situations and practice patterns were examined by racial/ethnic groups and immigrant generations. Practice patterns measured were respite care use, hours and length of caregiving. Three hypotheses on caregiving patterns based on assimilation theory were tested and analyzed using logistic regression and generalized linear models by racial/ethnic groups and generations. Caregiving patterns of non-Hispanic White caregivers supported all three hypotheses regarding respite care use, caregiving hours and caregiving duration, showing less caregiving involvement in later generations. However, Asian and Hispanic counterparts showed mixed results. Third generation Asian and Hispanic caregivers used respite care the least and spent the most caregiving hours per week and had the longest caregiving duration compared to earlier generations. These caregiving patterns revealed underlying cultural values related to filial responsibility, even among later generations of caregivers of color. Findings suggest the importance of considering the cultural values of each racial/ethnic group regardless of generation when working with racially and ethnically diverse populations of family caregivers of older adults. PMID- 26810574 TI - Testing a dynamic-field account of interactions between spatial attention and spatial working memory. AB - Studies examining the relationship between spatial attention and spatial working memory (SWM) have shown that discrimination responses are faster for targets appearing at locations that are being maintained in SWM, and that location memory is impaired when attention is withdrawn during the delay. These observations support the proposal that sustained attention is required for successful retention in SWM: If attention is withdrawn, memory representations are likely to fail, increasing errors. In the present study, this proposal was reexamined in light of a neural-process model of SWM. On the basis of the model's functioning, we propose an alternative explanation for the observed decline in SWM performance when a secondary task is performed during retention: SWM representations drift systematically toward the location of targets appearing during the delay. To test this explanation, participants completed a color discrimination task during the delay interval of a spatial-recall task. In the critical shifting-attention condition, the color stimulus could appear either toward or away from the midline reference axis, relative to the memorized location. We hypothesized that if shifting attention during the delay leads to the failure of SWM representations, there should be an increase in the variance of recall errors, but no change in directional errors, regardless of the direction of the shift. Conversely, if shifting attention induces drift of SWM representations-as predicted by the model systematic changes in the patterns of spatial-recall errors should occur that would depend on the direction of the shift. The results were consistent with the latter possibility-recall errors were biased toward the locations of discrimination targets appearing during the delay. PMID- 26810579 TI - High expression of adenylate cyclase-associated protein 1 accelerates the proliferation, migration and invasion of neural glioma cells. AB - Adenylate cyclase-associated protein 1 (CAP1), a conserved member of cyclase associated proteins was reported to be associated with the proliferation, migration or invasion of the tumors of pancreas, breast and liver, and was involved in astrocyte proliferation after acute Traumatic Brain Injury (TBI). In this study, we sought to investigate the character of CAP1 in the pathological process of human glioma by detecting human glioma specimens and cell lines. 43 of 100 specimens showed high expression of CAP1 via immunohistochemistry. With statistics analysis, we found out the expression level of CAP1 was correlated with the WHO grades of human glioma and was great positively related to Ki-67 (p<0.01). In vitro, silencing CAP1 in U251 and U87MG, the glioma cell lines with the relatively higher expression of CAP1, induced the proliferation of the cells significantly retarded, migration and invasion as well. Obviously, our results indicated that CAP1 participated in the molecular pathological process of glioma indeed, and in a certain sense, CAP1 might be a potential and promising molecular target for glioma diagnosis and therapies in the future. PMID- 26810580 TI - The demographic and clinical characteristics of leprosy in Saudi Arabia. AB - Leprosy is a chronic disease caused by Mycobacterium leprae. Although the occurrence of leprosy has declined in Saudi Arabia, it has not yet been eradicated. To our knowledge, this descriptive retrospective study is the first to assess the clinical presentation of leprosy at the time of diagnosis in Saudi Arabia. All study subjects were leprosy patients admitted to Ibn Sina hospital, the only referral hospital for leprosy in Saudi Arabia, between January 2000 and May 2012. A total of 164 subjects, the majority of whom (65%) were between 21 and 50 years of age, were included, and the male-to-female ratio was 2.8:1. Of these 164 patients, 63% were Saudis, and 77% of all admitted patients were from the western region. Lepromatous leprosy was observed most frequently (33%), and 31% of cases had a positive history of close contact with leprosy. At the time of diagnosis, 84% of all subjects presented with skin manifestation. The prevalence of neurological deficit at the time of diagnosis was 87%. Erythema nodosum leprosum (E.N.L.) developed in only 10% of all subjects. Further studies are needed to determine the clinical characteristics pertaining to each type of leprosy in the region, and training courses in caring for and diagnosing patients with leprosy should be organized for health workers. PMID- 26810581 TI - Phase I Study of Concomitant Pemetrexed and Cisplatin Plus External Beam Radiation Therapy in Patients with Locally Advanced or Metastatic Esophageal or Gastroesophageal Junction Carcinomas. AB - PURPOSE: To establish the maximum tolerated dose (MTD) and safety profile of bi weekly Pemetrexed (PEM) when combined with weekly cisplatin (CDDP) and standard dose external beam radiation (EBRT) in patients with locally advanced or metastatic esophageal and gastroesophageal junction (GEJ) carcinomas. METHODS: We conducted an open label, single institution, phase I dose escalation study designed to evaluate up to 15-35 patients with advanced or metastatic esophageal and GEJ carcinomas. RESULTS: 10 patients were treated with bi-weekly PEM, weekly CDDP, and EBRT. The MTD of bi-weekly PEM was determined to be 500 mg/m(2). PMID- 26810582 TI - Psychological distress, social support, and quality of life among cancer caregivers in Albania. AB - OBJECTIVE: Drawing on the Stress Process Model, this study examines cancer caregiving in Albania. We used conditional process analysis to test the relationship between psychological distress and quality of life through social support and to examine whether gender moderates pathways in this mediation model. METHODS: Face-to-face interviews were conducted with a non-probability sample of 377 caregivers from the public oncology service. Standardized measures were selected based on psychometric properties and cross-cultural adequacy; all had good internal consistency. RESULTS: Participants reported high levels of psychological distress, moderate social support, and poor quality of life. Compared with men, women had higher levels of distress, worse quality of life, and comparable levels of support. Men were more likely to be caring for a spouse and to rely on friends, while women also cared for others and relied more on family. Social support mediated a strong negative relationship between psychological distress and QoL. These pathways did not differ by gender. CONCLUSIONS: Cancer is increasing rapidly in developing countries, where family caregiving is the preferred and often only option for long-term, intensive care. This study points to high risks for psychological distress and reduced quality of life, especially for female caregivers in Albania. Findings further highlight the importance of social supports an as avenue for prevention and intervention to improve quality of life for both men and women. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26810584 TI - Antioxidant, anticholinesterase and tyrosinase inhibition activities, and fatty acids of Crocus mathewii - A forgotten endemic angiosperm of Turkey. AB - Context We report the first ever chemical/biochemical study on Crocus mathewii Kerndorff (Iridaceae) - a Turkish endemic angiosperm. This plant has never been explored for its phytochemistry and bioactivities. Objective This study explores C. mathewii corm and aerial parts for the chemical and biological properties of hexane, ethyl acetate, methanol and water fractions of the extracts. Material and methods Plant material (20 g) was extracted by methanol (250 mL * 5, 3 days each) and fractioned into hexane, ethyl acetate, methanol and water. All fractions were subjected to beta-carotene-linoleic acid, DPPH(.), ABTS(.)(+), CUPRAC, metal chelating and tyrosinase inhibition activities. Hexane fractions were submitted to GC-MS analysis. Results Ethyl acetate fractions showed excellent IC50 values in DPPH(.) (aerial 36.21 +/- 0.76 and corm 33.87 +/- 0.02 mg/L) and ABTS(.)(+) (aerial 33.01 +/- 0.79 and bulb 27.87 +/- 0.33 mg/L); higher than the IC50 of the standard alpha-tocopherol (DPPH 116.25 +/- 1.97; ABTS 52.64 +/- 0.37 mg/L), higher than BHA in DPPH (57.31 +/- 0.25 mg/L), but slightly lower in ABTS (19.86 +/- 2.73 mg/L). Methanol extract of aerial parts also showed higher activity than alpha-tocopherol in DPPH (85.56 +/- 11.51 mg/L) but slightly less (72.90 +/- 3.66 mg/L) than both the standards in ABTS. Linoleic (aerial 53.9%, corm 43.9%) and palmitic (aerial 22.2%, corm 18%) were found as the major fatty acids. Discussion and conclusion Some fractions of C. mathewii showed higher antioxidant activities than the standards. There is a need to explore more about this plant. PMID- 26810586 TI - An NGS-Independent Strategy for Proteome-Wide Identification of Single Amino Acid Polymorphisms by Mass Spectrometry. AB - Detection of proteins containing single amino acid polymorphisms (SAPs) encoded by nonsynonymous SNPs (nsSNPs) can aid researchers in studying the functional significance of protein variants. Most proteogenomic approaches for large-scale SAPs mapping require construction of a sample-specific database containing protein variants predicted from the next-generation sequencing (NGS) data. Searching shotgun proteomic data sets against these NGS-derived databases allowed for identification of SAP peptides, thus validating the proteome-level sequence variation. Contrary to the conventional approaches, our study presents a novel strategy for proteome-wide SAP detection without relying on sample-specific NGS data. By searching a deep-coverage proteomic data set from an industrial thermotolerant yeast strain using our strategy, we identified 337 putative SAPs compared to the reference genome. Among the SAP peptides identified with stringent criteria, 85.2% of SAP sites were validated using whole-genome sequencing data obtained for this organism, which indicates high accuracy of SAP identification with our strategy. More interestingly, for certain SAP peptides that cannot be predicted by genomic sequencing, we used synthetic peptide standards to verify expression of peptide variants in the proteome. Our study has provided a unique tool for proteogenomics to enable proteome-wide direct SAP identification and capture nongenetic protein variants not linked to nsSNPs. PMID- 26810591 TI - TDP-43 in the olfactory bulb in Alzheimer's disease. PMID- 26810592 TI - Rapid and accurate tumor-target bio-imaging through specific in vivo biosynthesis of a fluorescent europium complex. AB - A new and facile method for rapidly and accurately achieving tumor targeting fluorescent images has been explored using a specifically biosynthesized europium (Eu) complex in vivo and in vitro. It demonstrated that a fluorescent Eu complex could be bio-synthesized through a spontaneous molecular process in cancerous cells and tumors, but not prepared in normal cells and tissues. In addition, the proteomics analyses show that some biological pathways of metabolism, especially for NADPH production and glutamine metabolism, are remarkably affected during the relevant biosynthesis process, where molecular precursors of europium ions are reduced to fluorescent europium complexes inside cancerous cells or tumor tissues. These results proved that the specific self-biosynthesis of a fluorescent Eu complex by cancer cells or tumor tissues can provide a new strategy for accurate diagnosis and treatment strategies in the early stages of cancers and thus is beneficial for realizing precise surgical intervention based on the relevant cheap and readily available agents. PMID- 26810587 TI - Toward clinical genomics in everyday medicine: perspectives and recommendations. AB - Precision or personalized medicine through clinical genome and exome sequencing has been described by some as a revolution that could transform healthcare delivery, yet it is currently used in only a small fraction of patients, principally for the diagnosis of suspected Mendelian conditions and for targeting cancer treatments. Given the burden of illness in our society, it is of interest to ask how clinical genome and exome sequencing can be constructively integrated more broadly into the routine practice of medicine for the betterment of public health. In November 2014, 46 experts from academia, industry, policy and patient advocacy gathered in a conference sponsored by Illumina, Inc. to discuss this question, share viewpoints and propose recommendations. This perspective summarizes that work and identifies some of the obstacles and opportunities that must be considered in translating advances in genomics more widely into the practice of medicine. PMID- 26810593 TI - Homogeneous Photocatalytic Water Oxidation with a Dinuclear Co(III) Pyridylmethylamine Complex. AB - A bis-hydroxo-bridged dinuclear Co(III)-pyridylmethylamine complex (1) was synthesized and the crystal structure was determined by X-ray crystallography. Complex 1 acts as a homogeneous catalyst for visible-light-driven water oxidation by persulfate (S2O8(2-)) as an oxidant with [Ru(II)(bpy)3](2+) (bpy = 2,2' bipyridine) as a photosensitizer affording a high quantum yield (44%) with a large turnover number (TON = 742) for O2 formation without forming catalytically active Co-oxide (CoO(x)) nanoparticles. In the water-oxidation process, complex 1 undergoes proton-coupled electron-transfer (PCET) oxidation as a rate-determining step to form a putative dinuclear bis-MU-oxyl Co(III) complex (2), which has been suggested by DFT calculations. Catalytic water oxidation by 1 using [Ru(III)(bpy)3](3+) as an oxidant in a H2(16)O and H2(18)O mixture was examined to reveal an intramolecular O-O bond formation in the two-electron-oxidized bis MU-oxyl intermediate, prior to the O2 evolution. PMID- 26810595 TI - Mobile Health Application Solutions. PMID- 26810594 TI - Molecular Mechanisms of Sympathetic Remodeling and Arrhythmias. PMID- 26810596 TI - Relationship Between Early and Late Nonsustained Ventricular Tachycardia and Cardiovascular Death in Patients With Acute Coronary Syndrome in the Platelet Inhibition and Patient Outcomes (PLATO) Trial. AB - BACKGROUND: Nonsustained ventricular tachycardia (NSVT) is common after acute coronary syndrome (ACS) and a marker of increased risk of arrhythmogenic death. However, the prognostic significance of NSVT when evaluated with other contemporary risk markers and at later time points after ACS remains uncertain. METHODS AND RESULTS: In the Platelet Inhibition and Patient Outcomes (PLATO) trial, continuous ECGs were performed during the first 7 days after ACS (n=2866) and repeated for another 7 days at day 30 (n=1991). Median follow-up was 1 year. There was a time-varying interaction between NSVT and cardiovascular death such that NSVT was significantly associated with increased risk within the first 30 days after randomization (22/999 [2.2%] versus 16/1825 [0.9%]; adjusted hazard ratio, 2.84; 95% confidence interval, 1.39-5.79; P=0.004) but not after 30 days (28/929 [3.0%] versus 42/1734 [2.4%]; P=0.71). Detection of NSVT during the convalescent phase (n=428/1991; 21.5%) was also associated with an increased risk of cardiovascular death, and was most marked within the first 2 months after detection (1.9% versus 0.3%; adjusted hazard ratio, 5.48; 95% confidence interval, 1.07-28.20; P=0.01), and then decreasing over time such that the relationship was no longer significant by ~5 months after ACS. CONCLUSIONS: NSVT occurred frequently during the acute and convalescent phases of ACS. The risk of cardiovascular death associated with NSVT was the greatest during the first 30 days after presentation; however, patients with NSVT detected during the convalescent phase were also at a significantly increased risk of cardiovascular death that persisted for an additional several months after the index event. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00391872. PMID- 26810599 TI - One-pot synthesis of 1H-isochromenes and 1,2-dihydroisoquinolines by a sequential isocyanide-based multicomponent/Wittig reaction. AB - A one-pot synthesis of 1H-isochromenes and 1,2-dihydroisoquinolines by a I MCR/Wittig sequence was developed. The reaction of phosphonium salt , an acid, an amine (or without), and an isocyanide gave the 1H-isochromenes or 1,2 dihydroisoquinolines in good yields by a sequential Passerini or Ugi condensation and an intramolecular Wittig reaction in the presence of K2CO3. PMID- 26810600 TI - Ultrasonography imaging of the anterolateral ligament using real-time virtual sonography. AB - BACKGROUND: The anterolateral ligament (ALL) functions as a stabilizer in the internal rotation of the knee. Previous studies have reported the ALL can be identified using magnetic resonance imaging (MRI); however, there are no reports on using ultrasonography (US) for this purpose. Real-time virtual sonography (RVS) uses magnetic navigation and computer software for the synchronized display of real-time US and multiplanar reconstruction MRI images. This study investigated the ability of using US with RVS to evaluate the ALL. METHODS: Nine healthy subjects were enrolled. The Digital Imaging Communications in Medicine MRI dataset was loaded into the Hitachi Aloka Preirus, and US images were displayed on the same monitor. When the ALL was identified using MRI, the monitor was frozen to evaluate the ALL. The ALL was divided into the femoral, meniscal, and tibial portions. The portions and thickness of the ALLs and the lateral inferior genicular artery (LIGA), a landmark for the ALL, were evaluated. RESULTS: All portions of the ALL could be identified using MRI. Using US, the tibial portion of the ALL was detected in all subjects and the femoral portion was detected in seven subjects; however, the meniscal portions could not be identified. The average ALL thickness as measured by US was 1.3+/-0.1 mm and the LIGA was identified in all cases. CONCLUSIONS: Most portions of the ALL can be identified using US. As most ALL injuries occur at the femoral or tibial portion, US may be useful as a diagnostic tool for ALL injury. LEVEL OF EVIDENCE: 4. PMID- 26810603 TI - A novel multi-CDK inhibitor P1446A-05 restricts melanoma growth and produces synergistic effects in combination with MAPK pathway inhibitors. AB - Nearly 100% of melanomas have a defect in the p16(INK4A):cyclin D-CDK4/6:RB pathway, leading to abnormal cell cycle control and unregulated cellular proliferation. Here, we report that P1446A-05, a novel multi-CDK inhibitor has significant inhibitory activity against cutaneous and uveal melanoma. Mechanistic studies revealed that P1446A-05 inhibits phosphorylation targets of CDK members, and induces cell cycle arrest and apoptosis irrespective of melanoma genotype or phenotype. Additionally, we show preclinical evidence that P1446A-05 can synergize with other small molecule inhibitors previously studied in melanoma. Collectively, these data demonstrate that targeting cell cycle and transcriptional CDKs with a small molecule multi-CDK inhibitor is a viable approach for developing novel anti-melanoma therapeutics. PMID- 26810604 TI - Comparison of Local Infiltration Analgesia With Femoral Nerve Block for Total Knee Arthroplasty: A Prospective, Randomized Clinical Trial. AB - BACKGROUND: Total knee arthroplasty (TKA) is usually associated with severe postoperative pain, which can prevent rehabilitation of patients' knee function and influence the satisfaction of surgery. Local infiltration analgesia (LIA) as a new method to managing postoperative pain has been applied in clinical practice recently. However, the safety and efficacy of LIA compared with femoral nerve block (FNB) in postoperative pain management of TKA still remains controversial. Thus, we conducted an original clinical trial to compare LIA and FNB. METHOD: One hundred fifty-seven patients undergoing TKA were enrolled in a randomized, double blind, single-center study. The patients received either FNB (group A) or periarticular infiltration of local anesthetic (group B). The morphine consumption used in patient-controlled analgesia after surgery, postoperative Visual Analogue Scale (VAS), Knee Society Score, and range of motion before and after surgery in both groups were analyzed, as well as the adverse effects. RESULTS: Group A consisted 78 patients, and group B contained 79 patients. The patients' characteristics including age and body mass index had no significant difference (P > .05). Morphine consumption, VAS at rest, range of motion, and Knee Society Score were similar between the 2 groups. Our study showed group B, the local anesthetic group had less VAS with movement on postoperative day 1 (P = .01) than that of group A, which means a better pain control. Because of the study design, the surgery time showed no significant difference. Eighteen patients in group A and 21 patients in group B experienced mild-to-medium nausea or vomiting. One patient in group B had dizziness and one patient in group A suffered a neuropraxic injury to the femoral nerve. No urinary retention case was seen during inpatient days. There were no significant differences between the 2 groups about side effects. CONCLUSIONS: Our research showed that no significant differences were observed between the 2 treatment groups. LIA could provide a similar analgesic effect to FNBs with a low incidence of complications. PMID- 26810602 TI - One Loop to Rule Them All: The Ping-Pong Cycle and piRNA-Guided Silencing. AB - The PIWI-interacting RNA (piRNA) pathway is a conserved defense mechanism that protects the genetic information of animal germ cells from the deleterious effects of molecular parasites, such as transposons. Discovered nearly a decade ago, this small RNA silencing system comprises PIWI-clade Argonaute proteins and their associated RNA-binding partners, the piRNAs. In this review, we highlight recent work that has advanced our understanding of how piRNAs preserve genome integrity across generations. We discuss the mechanism of piRNA biogenesis, give an overview of common themes as well as differences in piRNA-mediated silencing between species, and end by highlighting known and emerging functions of piRNAs. PMID- 26810606 TI - Measuring interoperable EHR adoption and maturity: a Canadian example. AB - BACKGROUND: An interoperable electronic health record is a secure consolidated record of an individual's health history and care, designed to facilitate authorized information sharing across the care continuum. Each Canadian province and territory has implemented such a system and for all, measuring adoption is essential to understanding progress and optimizing use in order to realize intended benefits. RESULTS: About 250,000 health professionals-approximately half of Canada's anticipated potential physician, nurse, pharmacist, and administrative users-indicated that they electronically access data, such as those found in provincial/territorial lab or drug information systems, in 2015. Trends suggest further growth as maturity of use increases. CONCLUSIONS: There is strong interest in health information exchange through the iEHR in Canada, and continued growth in adoption is expected. Central to managing the evolution of digital health is access to robust data about who is using solutions, how they are used, where and when. Stakeholders such as government, program leads, and health system administrators must critically assess progress and achievement of benefits, to inform future strategic and operational decisions. PMID- 26810607 TI - Rational design and diversity-oriented synthesis of peptoid-based selective HDAC6 inhibitors. AB - A mini library of HDAC inhibitors with peptoid-based cap groups was synthesized using an efficient multicomponent approach. Four compounds were identified as potent HDAC6 inhibitors with a selectivity over other HDAC isoforms. The most potent HDAC6 inhibitor revealed remarkable chemosensitizing properties and completely reverted the cisplatin resistance in Cal27 CisR cells. PMID- 26810608 TI - Lymphocyte depletion and repopulation after chemotherapy for primary breast cancer. AB - BACKGROUND: Approximately 30 % of breast cancer patients receive chemotherapy, yet little is known about influences of current regimens on circulating lymphocyte levels and phenotypes. Similarly, clinico-pathological factors that modify these influences, and implications for future immune health remain mainly unexplored. METHODS: We used flow-cytometry to assess circulating lymphocyte levels and phenotypes in 88 primary breast cancer patients before chemotherapy and at time-points from 2 weeks to 9 months after chemotherapy completion. We examined circulating titres of antibodies against pneumococcal and tetanus antigens using ELISAs. RESULTS: Levels of B, T and NK cells were significantly reduced 2 weeks after chemotherapy (p < 0.001). B cells demonstrated particularly dramatic depletion, falling to 5.4 % of pre-chemotherapy levels. Levels of all cells recovered to some extent, although B and CD4(+) T cells remained significantly depleted even 9 months post-chemotherapy (p < 0.001). Phenotypes of repopulating B and CD4(+) T cells were significantly different from, and showed no sign of returning to pre-chemotherapy profiles. Repopulating B cells were highly depleted in memory cells, with proportions of memory cells falling from 38 % to 10 % (p < 0.001). Conversely, repopulating CD4(+) T cells were enriched in memory cells, which increased from 63 % to 75 % (p < 0.001). Differences in chemotherapy regimen and patient smoking were associated with significant differences in depletion extent or repopulation dynamics. Titres of anti pneumococcal and anti-tetanus antibodies were both significantly reduced post chemotherapy and did not recover during the study (p < 0.001). CONCLUSION: Breast cancer chemotherapy is associated with long-term changes in immune parameters that should be considered during clinical management. PMID- 26810609 TI - Interferon regulatory factor 7 regulates airway epithelial cell responses to human rhinovirus infection. AB - BACKGROUND: Human rhinoviruses (HRV) cause the majority of colds and trigger exacerbations of chronic lower airway diseases. Airway epithelial cells are the primary site for HRV infection and replication, and the initiation of host inflammatory responses. At present, the molecular mechanisms that underpin HRV responses in airway epithelial cells are incompletely understood. The aim of this study was to employ microarray profiling, upstream regulator analysis, and siRNA mediated gene silencing to further our understanding of the role of interferon regulatory factor 7 (IRF7) in this response. METHODS: Primary human bronchial epithelial cells (HBE) where transfected with siRNA that targets IRF7 or a non silencing control (all-star control) using Lipofectamine. The cells were allowed to recover, and then cultured in the presence or absence of HRV-16 for 24 h. Global patterns of gene expression were profiled on microarrays. A subset of genes identified in the microarray study were validated at the mRNA and/or protein level using real time RT-qPCR, ELISA, and western blots. RESULTS: Hundreds of genes were upregulated in HBE during HRV infection. Pathways analysis demonstrated that these genes were mainly involved in type I and II interferon signaling, RIG-I/MDA5 signaling, antigen processing and presentation, and apoptosis. Upstream regulator analysis of these data suggested that IRF7 was a major molecular driver of this response. Knockdown of IRF7 reduced the HRV-driven upregulation of genes involved in antiviral responses (interferon signaling, Toll like receptor signaling, NOD-like receptor signaling, RIG-I/MDA5 signaling), and increased the expression of genes that promote inflammation (e.g. CXCL5, IL-33, IL1RL1) and the response to oxidative stress. However, the majority of genes that were perturbed by HRV in HBE cells including those that are known to be regulated by IRF7 were insensitive to IRF7 knockdown. Upstream regulator analysis of the part of the response that was insensitive to IRF7 knockdown suggested it was driven by NF-kappaB, STAT1, STAT3, and IRF1. CONCLUSIONS: Our findings demonstrate that IRF7 regulates the expression of genes involved in antiviral immunity, inflammation, and the response to oxidative stress during HRV infections in HBE cells, and also suggests that other transcription factors play a major role in this response. PMID- 26810610 TI - Tigecycline as last resort in severe refractory Clostridium difficile infection: a case report. PMID- 26810611 TI - Multidrug-resistant organisms among refugees in Germany: we need evidence-based care, not fear-based screening. PMID- 26810612 TI - Epidemiology of central line-associated bloodstream infections at a tertiary care centre in northern India. PMID- 26810613 TI - Diagnosis and features of hospital-acquired pneumonia: a retrospective cohort study. AB - BACKGROUND: Hospital-acquired pneumonia (HAP) is defined as radiologically confirmed pneumonia occurring >=48h after hospitalization, in non-intubated patients. Empirical treatment regimens use broad-spectrum antimicrobials. AIM: To evaluate the accuracy of the diagnosis of HAP and to describe the demographic and microbiological features of patients with HAP. METHODS: Medical and surgical inpatients receiving intravenous antimicrobials for a clinical diagnosis of HAP at a UK tertiary care hospital between April 2013 and 2014 were identified. Demographic and clinical details were recorded. FINDINGS: A total of 166 adult patients with a clinical diagnosis of HAP were identified. Broad-spectrum antimicrobials were prescribed, primarily piperacillin-tazobactam (57.2%) and co amoxiclav (12.5%). Sputum from 24.7% of patients was obtained for culture. Sixty five percent of patients had radiological evidence of new/progressive infiltrate at the time of HAP treatment, therefore meeting HAP diagnostic criteria (2005 American Thoracic Society/Infectious Diseases Society of America guidelines). Radiologically confirmed HAP was associated with higher levels of inflammatory markers and sputum culture positivity. Previous surgery and/or endotracheal intubation were associated with radiologically confirmed HAP. A bacterial pathogen was identified from 17/35 sputum samples from radiologically confirmed HAP patients. These were Gram-negative bacilli (N = 11) or Staphylococcus aureus (N = 6). Gram-negative bacteria tended to be resistant to co-amoxiclav, but susceptible to ciprofloxacin, piperacillin-tazobactam and meropenem. Five of the six S. aureus isolates were meticillin susceptible and all were susceptible to doxycycline. CONCLUSION: In ward-level hospital practice 'HAP' is an over-used diagnosis that may be inaccurate in 35% of cases when objective radiological criteria are applied. Radiologically confirmed HAP represents a distinct clinical and microbiological phenotype. Potential risk factors were identified that could represent targets for preventive interventions. PMID- 26810614 TI - First report of CTX-M-15-producing Acinetobacter baumannii in Brazil. PMID- 26810615 TI - The protected environment for high-risk haematology patients: as safe as we think? PMID- 26810616 TI - Baby bottle steam sterilizers for disinfecting home nebulizers inoculated with non-tuberculous mycobacteria. AB - Non-tuberculous mycobacteria (NTMb), present in environmental water sources, can contribute to respiratory infection in patients with chronic pulmonary disease. Contaminated nebulizers are a potential source of respiratory infection. Treatment with baby bottle steam sterilizers disinfects home nebulizers inoculated with bacterial pathogens but whether this method works for disinfection of NTMb is unclear. Baby bottle steam sterilization was compared with vigorous water washing for disinfecting home nebulizers inoculated with NTMb mixed with cystic fibrosis sputum. No NTMb was recovered from any nebulizers after steam treatment whereas viable NTMb grew after water washing, demonstrating that steam sterilization effectively disinfects NTMb-inoculated nebulizers. PMID- 26810617 TI - Cryoprotective properties and preliminary characterization of exopolysaccharide (P-Arcpo 15) produced by the Arctic bacterium Pseudoalteromonas elyakovii Arcpo 15. AB - Twenty-two bacterial strains that secrete exopolysaccharides (EPS) were isolated from marine samples obtained from the Chukchi Sea in the Arctic Ocean; of these, seven strains were found to be capable of producing cryoprotective EPS. The ArcPo 15 strain was isolated based on its ability to secrete large amounts of EPS, and was identified as Pseudoalteromonas elyakovii based on 16S rDNA analysis. The EPS, P-ArcPo 15, was purified by protease treatment and gel filtration chromatography. The purified EPS (P-ArcPo 15) had a molecular mass of 1.7 * 10(7) Da, and its infrared spectrum showed absorption bands of hydroxyl and carboxyl groups. The principal sugar components of P-ArcPo 15 were determined to be mannose and galacturonic acid, in the ratio of 3.3:1.0. The cryoprotective properties of P-ArcPo 15 were characterized by an Escherichia coli viability test. In the presence of 0.5% (w/v) EPS, the survival percentage of E. coli cells was as high as 94.19 +/- 7.81% over five repeated freeze-thaw cycles. These biochemical characteristics suggest that the EPS P-ArcPo 15 may be useful in the development of cryoprotectants for biotechnological purposes, and we therefore assessed the utility of this novel cryoprotective EPS. PMID- 26810618 TI - Assessing barriers to immunization. AB - Parental barriers to childhood immunizations vary among countries, states and communities. There is a plethora of studies that exist to examine barriers to immunizations including many intervention studies designed to improve immunization rates in children. Often, intervention studies designed to minimize barriers and increase immunization uptake among children lack the inclusion of a standardized instrument to measure accurately parental barriers to childhood immunizations before and after interventions. The Searching for Hardships and Obstacles To Shots (SHOTS) survey is a standardized survey instrument to measure parental barriers to childhood immunizations. In several studies, the SHOTS survey has demonstrated consistent reliability and has been validated in diverse populations. The inclusion of the SHOTS survey instrument in studies to examine barriers to childhood immunization will provide researchers and clinicians with a better understanding of parents' individualized barriers to immunizations. Furthermore, use of the SHOTS survey instrument to collect information about parental barriers to immunizations can lead to targeted interventions to minimize these obstacles at the individual and community level and to help us to achieve our national, state and community childhood immunization goals. PMID- 26810621 TI - The Importance of the Nursing Role in Parental Vaccine Decision Making. PMID- 26810620 TI - Hearing function after betahistine therapy in patients with Meniere's disease. AB - INTRODUCTION: Preventing or reversing hearing loss is challenging in Meniere's disease. Betahistine, as a histamine agonist, has been tried in controlling vertigo in patients with Meniere's disease, but its effectiveness on hearing problems is not known. OBJECTIVE: To examine the effect of betahistine on hearing function in not-previously-treated patients with Meniere's disease and to define possible contributors in this regard. METHODS: A total of 200 not-previously treated patients with definite unilateral Meniere's disease received betahistine by mouth (initial dose, 16mg three times a day; maintenance dose, 24-48mg daily in divided doses). Changes in indicators of hearing status before and six months after treatment were documented. Hearing loss was considered as the mean hearing level >25dB HL at five frequencies. RESULTS: The mean duration of disease was 3.37 years. Six months after treatment the mean hearing level decreased by 6.35dB compared to that at the baseline (p<0.001). Both patients' age and the duration of disease correlated negatively with the improvement in hearing function. Post treatment hearing loss was independently associated with age, the initial hearing level and the chronicity of disease. The corresponding optimal cut-off points for predicating a persistent hearing loss 6 months after treatment were 47 years, 38dB HL, and 1.4 years, respectively. CONCLUSION: Oral betahistine was significantly effective in preventing/reversing hearing deterioration in patients with Meniere's disease. Age, the hearing level on admission, and the disease duration were independent predictors of hearing status after treatment. PMID- 26810622 TI - Submandibular Swelling and Fever Following Frenulectomy in a 13-Day-Old Infant. PMID- 26810623 TI - Hypernatremia in Children With Diarrhea: Presenting Features, Management, Outcome, and Risk Factors for Death. AB - We sought to investigate the magnitude, clinical features, treatment, and outcome of children suffering from hypernatremic diarrhea and to identify risk factors for fatal outcome among them. We reviewed 2 data sets of children <15 years admitted to the in-patient ward of the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr, b) with diarrhea and hypernatremia (serum sodium >=150 mmol/L): (a) March 2001 to March 2002 (n = 371) and (b) March 2009 to August 2011 (n = 360). We reviewed their records and collected relevant information for analyses. The prevalence of hypernatremia was 5.1% (371/7212) and 2.4% (360/15 219), case fatality rate was 15% and 19%, respectively. In logistic regression analysis, the risk for death significantly increased in association with serum sodium >=170 mmol/L, nutritional edema, hypoglycemia, respiratory distress, and absent peripheral pulses and reduced with the sole use of oral rehydration salts (ORS) or ORS following intravenous fluid, if indicated (for all, P < .05). Thus, managing children with hypernatremia using only ORS or ORS following intravenous fluid may help reduce the number of deaths. PMID- 26810624 TI - Utility of Obtaining a Serum Basic Metabolic Panel in the Setting of a First-Time Nonfebrile Seizure. AB - New-onset nonfebrile seizures in an otherwise healthy child are common, affecting 25 000 to 40 000 U.S. children annually. We hypothesized seizure-provoking electrolyte disturbances such as hyponatremia, hypoglycemia, and hypocalcemia are uncommon in these children. From January 1, 2009 to May 31, 2009, 358 children aged 29 days to 18 years with a diagnosis code of 780.39 ("other convulsions" including "first time seizure," etc) were included for potential retrospective review. Children with known epilepsy and febrile seizures were excluded. Electrolytes were obtained in nearly all children with a history suggestive of an underlying abnormality (13 of 14, 93%) but also in half of children with a reassuring history (62 of 119, 52%). No child with an unremarkable history and exam was found to have electrolyte abnormalities falling below levels most likely to be associated with acute symptomatic seizures. Electrolytes are unlikely to be abnormal in an otherwise well-appearing child after a first-time nonfebrile seizure. PMID- 26810625 TI - Obesity as a Risk Factor for Urinary Tract Infection in Children. AB - Childhood obesity is a nationwide epidemic with an estimated 16% to 18% of children and adolescents qualifying as obese and another 21% to 24% considered overweight. Obesity has been linked to an increased risk of developing serious infections. Healthcare Cost and Utilization Project-Kids' Inpatient Database 2009 was queried to analyze national trends in patient encounters, specifically those listing patients as comorbid obese and then identified those with urinary tract infection (UTI) as primary or secondary diagnosis. Propensity matching was used to calculate risk for UTI in the inpatient obese pediatric population. A total of 86 638 pediatric hospital admissions were enrolled in the study of which 41 819 included the diagnosis of obesity, and a UTI was diagnosed in 2445 of the cases. In a propensity-matched sample, matched for age, sex, race, and diabetes mellitus, the risk of UTI was increased by 45% in obese females. Obese males did not have a significantly increased risk for UTI. PMID- 26810629 TI - Foreword to the special issue on Bone and cartilage mechanobiology across the scales. PMID- 26810630 TI - Analysis of mechanical parameters on the thromboembolism using a patient-specific computational model. AB - Ischemic stroke is a major cause of death and long-term disabilities worldwide. In this paper, we aim to represent a comprehensive simulation of the motion of emboli through cerebrovascular network within patient-specific computational model. The model consists of major arteries of the circle of Willis reconstructed from magnetic resonance angiography images, pulsatile flow and emboli with different sizes and material properties. Here, the fluid-structure interactions method was used to simulate the motion of deformable and rigid emboli through cerebral arteries. Hemodynamic changes in the circle of Willis due to the entrance of embolus are observed. The effect of material properties on the distribution ratio and dynamics of motion of the emboli in the cerebral arterial network is also analyzed. Our results reveal that as the rigidity of emboli increases, higher proportion of them tend to enter to the larger arteries (e.g., middle cerebral artery). Scrutinizing the amount of stress acting on the emboli represented in this paper can broaden our understanding of the rheological phenomenon (e.g., lysis or growth of emboli during embolism). The approach of considering different material properties of the thrombus in a patient-specific computational model not only enable us to better understand the roll of biomechanical parameters causing the embolism, but also lead to a better clinical decision making to manage patients with stroke. PMID- 26810619 TI - Global and National Burden of Diseases and Injuries Among Children and Adolescents Between 1990 and 2013: Findings From the Global Burden of Disease 2013 Study. AB - IMPORTANCE: The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce. OBJECTIVE: To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged <5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study. EVIDENCE REVIEW: Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14,244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35,620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates. FINDINGS: Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905.059 deaths; 95% UI, 810,304-998,125), diarrheal diseases among older children (38,325 deaths; 95% UI, 30,365-47,678), and road injuries among adolescents (115,186 deaths; 95% UI, 105,185-124,870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world's deaths from neonatal encephalopathy. Half of the world's diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia. CONCLUSIONS AND RELEVANCE: Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed. PMID- 26810631 TI - LipoCEST and cellCEST imaging agents: opportunities and challenges. AB - From the early days of CEST agents' disclosure, it was evident that their potential for in vivo applications was strongly hampered by the intrinsic low sensitivity. Therefore, much work has been devoted to seek out suitable routes to achieve strong CEST contrast enhancement. The use of nanosized systems turned out to be a strategic choice, because a very large amount of CEST agents can be delivered at the site of interest. However, the breakthrough innovation in term of increase of sensitivity was found by designing the lipoCEST agents. The naturally inspired, liposomes vesicles, when loaded with paramagnetic lanthanide based shift reagents, can be transformed into CEST probes. The large number of water molecules entrapped inside the inner cavity of the nanovesicles represents an enormous pool of exchanging protons for the generation of CEST contrast, whereas the presence of the shift reagent increases the separation in chemical shift of their nuclear magnetic resonance signal from that of the bulk water, thus allowing for a proper exchange regime for the activation of CEST contrast. From lipoCEST, it has been rather straightforward to evolve to cellCEST in order to exploit the cytoplasmatic water molecules as source of the CEST effect, once cells have been loaded with the proper shift reagent. The red blood cells were found to be particularly suitable for the development of the cellCEST concept. Finally, an understanding of the main determinants of the CEST effects in nanosized and cellular-sized agents has allowed the design of innovative lipoCEST/RBC aggregates for potential theranostic applications. WIREs Nanomed Nanobiotechnol 2016, 8:602-618. doi: 10.1002/wnan.1385 For further resources related to this article, please visit the WIREs website. PMID- 26810632 TI - Assessment of Eating Behavior Disturbance and Associated Neural Networks in Frontotemporal Dementia. AB - IMPORTANCE: Abnormal eating behaviors are common in patients with frontotemporal dementia (FTD), yet their exact prevalence, severity, and underlying biological mechanisms are not understood. OBJECTIVE: To define the severity of abnormal eating behavior and sucrose preference and their neural correlates in patients with behavioral variant FTD (bvFTD) and semantic dementia. DESIGN, SETTING, AND PARTICIPANTS: Forty-nine patients with dementia (19 with bvFTD, 15 with semantic dementia, and 15 with Alzheimer disease) were recruited, and their eating behavior was compared with that of 25 healthy controls. The study was conducted from November 1, 2013, through May 31, 2015, and data analyzed from June 1 to August 31, 2015. MAIN OUTCOMES AND MEASURES: Patients participated in an ad libitum breakfast test meal, and their total caloric intake and food preferences were measured. Changes in eating behavior were also measured using the Appetite and Eating Habits Questionnaire (APEHQ) and the Cambridge Behavioral Inventory (CBI). Sucrose preference was tested by measuring liking ratings of 3 desserts of varying sucrose content (A: 26%, B: 39%, C: 60%). Voxel-based morphometry analysis of whole-brain 3-T high-resolution brain magnetic resonance imaging was used to determine the gray matter density changes across groups and their relations to eating behaviors. RESULTS: Mean (SD) ages of patients in all 4 groups ranged from 62 (8.3) to 66 (8.4) years. At the ad libitum breakfast test meal, all patients with bvFTD had increased total caloric intake (mean, 1344 calories) compared with the Alzheimer disease (mean, 710 calories), semantic dementia (mean, 573 calories), and control groups (mean, 603 calories) (P < .001). Patients with bvFTD and semantic dementia had a strong sucrose preference compared with the other groups. Increased caloric intake correlated with atrophy in discrete neural networks that differed between patients with bvFTD and semantic dementia but included the cingulate cortices, thalami, and cerebellum in patients with bvFTD, with the addition of the orbitofrontal cortices and nucleus accumbens in patients with semantic dementia. A distributed network of neural correlates was associated with sucrose preference in patients with FTD. CONCLUSIONS AND RELEVANCE: Marked hyperphagia is restricted to bvFTD, present in all patients with this diagnosis, and supports its diagnostic value. Differing neural networks control eating behavior in patients with bvFTD and semantic dementia and are likely responsible for the differences seen, with a similar network controlling sucrose preference. These networks share structures that control cognitive-reward, autonomic, neuroendocrine, and visual modulation of eating behavior. Delineating the neural networks involved in mediating these changes in eating behavior may enable treatment of these features in patients with complex medical needs and aid in our understanding of structures that control eating behavior in patients with FTD and healthy individuals. PMID- 26810633 TI - Fostering Longitudinal Involvement in State Chapter Resident and Fellow Sections: The Maryland Experience. PMID- 26810628 TI - Using patient self-reports to study heterogeneity of treatment effects in major depressive disorder. AB - BACKGROUNDS: Clinicians need guidance to address the heterogeneity of treatment responses of patients with major depressive disorder (MDD). While prediction schemes based on symptom clustering and biomarkers have so far not yielded results of sufficient strength to inform clinical decision-making, prediction schemes based on big data predictive analytic models might be more practically useful. METHOD: We review evidence suggesting that prediction equations based on symptoms and other easily-assessed clinical features found in previous research to predict MDD treatment outcomes might provide a foundation for developing predictive analytic clinical decision support models that could help clinicians select optimal (personalised) MDD treatments. These methods could also be useful in targeting patient subsamples for more expensive biomarker assessments. RESULTS: Approximately two dozen baseline variables obtained from medical records or patient reports have been found repeatedly in MDD treatment trials to predict overall treatment outcomes (i.e., intervention v. control) or differential treatment outcomes (i.e., intervention A v. intervention B). Similar evidence has been found in observational studies of MDD persistence-severity. However, no treatment studies have yet attempted to develop treatment outcome equations using the full set of these predictors. Promising preliminary empirical results coupled with recent developments in statistical methodology suggest that models could be developed to provide useful clinical decision support in personalised treatment selection. These tools could also provide a strong foundation to increase statistical power in focused studies of biomarkers and MDD heterogeneity of treatment response in subsequent controlled trials. CONCLUSIONS: Coordinated efforts are needed to develop a protocol for systematically collecting information about established predictors of heterogeneity of MDD treatment response in large observational treatment studies, applying and refining these models in subsequent pragmatic trials, carrying out pooled secondary analyses to extract the maximum amount of information from these coordinated studies, and using this information to focus future discovery efforts in the segment of the patient population in which continued uncertainty about treatment response exists. PMID- 26810634 TI - The Implementation and Impact of a Quality Improvement Program in Emergency Radiology. PMID- 26810635 TI - The Radiology Fellowship Arms Race Cannot Be Won. PMID- 26810636 TI - A Wiki-Based Solution to Managing Your Institution's Imaging Protocols. PMID- 26810637 TI - Reducing Radiation Exposure Without Compromising Image Quality for Lumbar Spine CT. PMID- 26810638 TI - Contrasting Electronic Health Records from Two Different Hospital Systems: Radiologists' Perspective. PMID- 26810639 TI - Leading in the World of Business and Medicine: Putting the Needs of Customers, Employees, and Patients First. PMID- 26810642 TI - High fidelity, low cost moulage as a valid simulation tool to improve burns education. AB - Simulation allows the opportunity for repeated practice in controlled, safe conditions. Moulage uses materials such as makeup to simulate clinical presentations. Moulage fidelity can be assessed by face validity (realism) and content validity (appropriateness). The aim of this project is to compare the fidelity of professional moulage to non-professional moulage in the context of a burns management course. Four actors were randomly assigned to a professional make-up artist or a course faculty member for moulage preparation such that two actors were in each group. Participants completed the actor-based burn management scenarios and answered a ten-question Likert-scale questionnaire on face and content validity. Mean scores and a linear mixed effects model were used to compare professional and non-professional moulage. Cronbach's alpha assessed internal consistency. Twenty participants experienced three out of four scenarios and at the end of the course completed a total of 60 questionnaires. Professional moulage had higher average ratings for face (4.30 v 3.80; p=0.11) and content (4.30 v 4.00; p=0.06) validity. Internal consistency of face (alpha=0.91) and content (alpha=0.85) validity questions was very good. The fidelity of professionally prepared moulage, as assessed by content validity, was higher than non-professionally prepared moulage. We have shown that using professional techniques and low cost materials we can prepare quality high fidelity moulage simulations. PMID- 26810644 TI - Molecular targeted photoimmunotherapy for HER2-positive human gastric cancer in combination with chemotherapy results in improved treatment outcomes through different cytotoxic mechanisms. AB - BACKGROUND: Photoimmunotherapy (PIT) is a novel type of molecular optical imaging guided cancer phototherapy based on a monoclonal antibody conjugated to a photosensitizer, IR700, in combination with near-infrared (NIR) light. PIT rapidly causes target-specific cell death by inducing cell membrane damages and appears to be highly effective; however, we have previously demonstrated that tumor recurrences were eventually seen in PIT-treated mice, likely owing to inhomogeneous mAb-IR700 conjugate distribution in the tumor, thus limiting the effectiveness of PIT as a monotherapy. Here, we examined the effects of human epidermal growth factor-2 (HER2)-targeted PIT in combination with 5-fluorouracil (5-FU) compared to PIT alone for HER2-expressing human gastric cancer cells. METHODS: NCI-N87 cells, HER2-positive human gastric cancer cells, were used for the experiments. Trastuzumab, a monoclonal antibody directed against HER2, was conjugated to IR700. To assess the short-term cytotoxicity and examine the apoptotic effects upon addition of 5-FU in vitro, we performed LIVE/DEAD and caspase-3 activity assays. Additionally, to explore the effects on long-term growth inhibition, trypan blue dye exclusion assay was performed. NCI-N87 tumor xenograft models were prepared for in vivo treatment studies and the tumor bearing mice were randomized into various treatment groups. RESULTS: Compared to PIT alone, the combination of HER2-targeted PIT and 5-FU rapidly induced significant cytotoxicity in both the short-term and long-term cytotoxicity assays. While both 5-FU and/or trastuzumab-IR700 conjugate treatment induced an increase in caspase-3 activity, there was no additional increase in caspase-3 activity upon NIR light irradiation after incubation with 5-FU and/or trastuzumab IR700. The combination of HER2-targeted PIT and 5-FU resulted in greater and longer tumor growth inhibition than PIT monotherapy in vivo. This combined effect of PIT and 5-FU is likely owing to their different mechanisms of inducing tumor cell death, namely necrotic membrane damage by PIT and apoptotic cell death by 5 FU and trastuzumab. CONCLUSIONS: PIT in combination with 5-FU resulted in enhanced antitumor effects compared to PIT alone for HER2-expressing human gastric cancer in vitro and in vivo. This combination photoimmunochemotherapy represents a practical method for treating human gastric cancer and should be investigated further in the clinical setting. PMID- 26810645 TI - Mycobacterium tuberculosis Mutations Associated with Reduced Susceptibility to Linezolid. AB - Linezolid (LZD) has become increasingly important for the treatment of multidrug resistant tuberculosis (MDR-TB), but its mechanisms of resistance are not well characterized. We isolated 32 mutants ofMycobacterium tuberculosiswith reduced susceptibility to LZD, which was accounted for byrrlandrplCmutations in almost equal proportions, causing lower and higher MICs, respectively. Our findings provide useful information for the rapid detection of LZD resistance for improved treatment of MDR-TB. PMID- 26810646 TI - Azithromycin Dose To Maximize Efficacy and Suppress Acquired Drug Resistance in Pulmonary Mycobacterium avium Disease. AB - Mycobacterium aviumcomplex is now the leading mycobacterial cause of chronic pneumonia in the United States. Macrolides and ethambutol form the backbone of the regimen used in the treatment of pulmonary disease. However, therapy outcomes remain poor, with microbial cure rates of 4% in cavitary disease. The treatment dose of azithromycin has mostly been borrowed from that used to treat other bacterial pneumonias; there are no formal dose-response studies in pulmonaryM. aviumdisease and the optimal dose is unclear. We utilized population pharmacokinetics and pharmacokinetics/pharmacodynamics-derived azithromycin exposures associated with optimal microbial kill or resistance suppression to perform 10,000 patient Monte Carlo simulations of dose effect studies for daily azithromycin doses of 0.5 to 10 g. The currently recommended dose of 500 mg per day achieved the target exposures in 0% of patients. Exposures associated with optimal kill and resistance suppression were achieved in 87 and 54% of patients, respectively, only by the very high dose of 8 g per day. The azithromycin susceptibility breakpoint above which patients failed therapy on the very high doses of 8 g per day was an MIC of 16 mg/liter, suggesting a critical concentration of 32 mg/liter, which is 8-fold lower than the currently used susceptibility breakpoint of 256 mg/liter. If the standard dose of 500 mg a day were used, then the critical concentration would fall to 2 mg/liter, 128-fold lower than 256 mg/liter. The misclassification of resistant isolates as susceptible could explain the high failure rates of current doses. PMID- 26810647 TI - Effect of Media Modified To Mimic Cystic Fibrosis Sputum on the Susceptibility of Aspergillus fumigatus, and the Frequency of Resistance at One Center. AB - Studies of cystic fibrosis (CF) patient exacerbations attributed toPseudomonas aeruginosainfection have indicated a lack of correlation of outcome within vitrosusceptibility results. One explanation is that the media used for testing do not mimic the airway milieu, resulting in incorrect conclusions. Therefore, media have been devised to mimic CF sputum.Aspergillus fumigatusis the leading fungal pathogen in CF, and susceptibility testing is also used to decide therapeutic choices. We assessed whether media designed to mimic CF sputa would give different fungal susceptibility results than those of classical methods, assaying voriconazole, the most utilized anti-Aspergillusdrug in this setting, and 30 CFAspergillusisolates. The frequency of marked resistance (defined as an MIC of >4 MUg/ml) in our CF unit by classical methods is 7%. Studies performed with classical methods and with digested sputum medium, synthetic sputum medium, and artificial sputum medium revealed prominent differences inAspergillussusceptibility results, as well as growth rate, with each medium. Clinical correlative studies are required to determine which results are most useful in predicting outcome. Comparison of MICs with non-CF isolates also indicated the CF isolates were generally more resistant. PMID- 26810648 TI - VIM-1, VIM-34, and IMP-8 Carbapenemase-Producing Escherichia coli Strains Recovered from a Portuguese River. PMID- 26810649 TI - Garcinol Inhibits GCN5-Mediated Lysine Acetyltransferase Activity and Prevents Replication of the Parasite Toxoplasma gondii. AB - Lysine acetylation is a critical posttranslational modification that influences protein activity, stability, and binding properties. The acetylation of histone proteins in particular is a well-characterized feature of gene expression regulation. In the protozoan parasiteToxoplasma gondii, a number of lysine acetyltransferases (KATs) contribute to gene expression and are essential for parasite viability. The natural product garcinol was recently reported to inhibit enzymatic activities of GCN5 and p300 family KATs in other species. Here we show that garcinol inhibits TgGCN5b, the only nuclear GCN5 family KAT known to be required forToxoplasmatachyzoite replication. Treatment of tachyzoites with garcinol led to a reduction of global lysine acetylation, particularly on histone H3 and TgGCN5b itself. We also performed transcriptome sequencing (RNA-seq), which revealed increasing aberrant gene expression coincident with increasing concentrations of garcinol. The majority of the genes that were most significantly affected by garcinol were also associated with TgGCN5b in a previously reported chromatin immunoprecipitation assay with microarray technology (ChIP-chip) analysis. The dysregulated gene expression induced by garcinol significantly inhibitsToxoplasmatachyzoite replication, and the concentrations used exhibit no overt toxicity on human host cells. Garcinol also inhibitsPlasmodium falciparumasexual replication with a 50% inhibitory concentration (IC50) similar to that forToxoplasma Together, these data support that pharmacological inhibition of TgGCN5b leads to a catastrophic failure in gene expression control that prevents parasite replication. PMID- 26810650 TI - In Vitro Activity of Ceftazidime-Avibactam against Contemporary Pseudomonas aeruginosa Isolates from U.S. Medical Centers by Census Region, 2014. AB - Thein vitroantibacterial activities of ceftazidime-avibactam and comparator agents were evaluated using reference broth microdilution methods against 1,743Pseudomonas aeruginosaisolates collected in 2014 from 69 U.S. medical centers, representing each of the nine census regions. Ceftazidime-avibactam demonstrated potent activity againstP. aeruginosa, including many isolates not susceptible to ceftazidime, meropenem, and piperacillin-tazobactam. In each of the nine census regions, ceftazidime-avibactam demonstrated the highest percentage of susceptible isolates. PMID- 26810651 TI - Pharmacokinetics of Rifampin, Isoniazid, Pyrazinamide, and Ethambutol in Infants Dosed According to Revised WHO-Recommended Treatment Guidelines. AB - There are limited pharmacokinetic data for use of the first-line antituberculosis drugs during infancy (<12 months of age), when drug disposition may differ. Intensive pharmacokinetic sampling was performed in infants routinely receiving antituberculosis treatment, including rifampin, isoniazid, pyrazinamide, and ethambutol, using World Health Organization-recommended doses. Regulatory approved single-drug formulations, including two rifampin suspensions, were used on the sampling day. Assays were conducted using liquid chromatography-mass spectrometry; pharmacokinetic parameters were generated using noncompartmental analysis. Thirty-nine infants were studied; 14 (36%) had culture-confirmed tuberculosis. Fifteen (38%) were premature (<37 weeks gestation); 5 (13%) were HIV infected. The mean corrected age and weight were 6.6 months and 6.45 kg, respectively. The mean maximum plasma concentrations (Cmax) for rifampin, isoniazid, pyrazinamide, and ethambutol were 2.9, 7.9, 41.9, and 1.3 MUg/ml, respectively (current recommended adult target concentrations: 8 to 24, 3 to 6, 20 to 50, and 2 to 6 MUg/ml, respectively), and the mean areas under the concentration-time curves from 0 to 8 h (AUC0-8) were 12.1, 24.7, 239.4, and 5.1 MUg . h/ml, respectively. After adjusting for age and weight, rifampin exposures for the two formulations used differed inCmax(geometric mean ratio [GMR],2.55; 95% confidence interval [CI], 1.47 to 4.41;P= 0.001) and AUC0-8(GMR, 2.52; 95% CI, 1.34 to 4.73;P= 0.005). HIV status was associated with lower pyrazinamideCmax(GMR, 0.85; 95% CI, 0.75 to 0.96;P= 0.013) and AUC0-8(GMR, 0.79; 95% CI, 0.69 to 0.90;P< 0.001) values. No other important differences were observed due to age, weight, prematurity, ethnicity, or gender. In summary, isoniazid and pyrazinamide concentrations in infants compared well with proposed adult target concentrations; ethambutol concentrations were lower but similar to previously reported pediatric studies. The low rifampin exposures require further investigation. (This study has been registered at ClinicalTrials.gov under registration no. NCT01637558.). PMID- 26810652 TI - High Prevalence of Chromosomal blaCTX-M-14 in Escherichia coli Isolates Possessing blaCTX-M-14. PMID- 26810653 TI - Sustained Nitric Oxide-Releasing Nanoparticles Induce Cell Death in Candida albicans Yeast and Hyphal Cells, Preventing Biofilm Formation In Vitro and in a Rodent Central Venous Catheter Model. AB - Candida albicansis a leading nosocomial pathogen. Today, candidal biofilms are a significant cause of catheter infections, and such infections are becoming increasingly responsible for the failure of medical-implanted devices.C. albicansforms biofilms in which fungal cells are encased in an autoproduced extracellular polysaccharide matrix. Consequently, the enclosed fungi are protected from antimicrobial agents and host cells, providing a unique niche conducive to robust microbial growth and a harbor for recurring infections. Here we demonstrate that a recently developed platform comprised of nanoparticles that release therapeutic levels of nitric oxide (NO-np) inhibits candidal biofilm formation, destroys the extracellular polysaccharide matrices of mature fungal biofilms, and hinders biofilm development on surface biomaterials such as the lumen of catheters. We found NO-np to decrease both the metabolic activity of biofilms and the cell viability ofC. albicansin vitroandin vivo Furthermore, flow cytometric analysis found NO-np to induce apoptosis in biofilm yeast cellsin vitro Moreover, NO-np behave synergistically when used in combination with established antifungal drug therapies. Here we propose NO-np as a novel treatment modality, especially in combination with standard antifungals, for the prevention and/or remediation of fungal biofilms on central venous catheters and other medical devices. PMID- 26810654 TI - Chlorhexidine Induces VanA-Type Vancomycin Resistance Genes in Enterococci. AB - Chlorhexidine is a bisbiguanide antiseptic used for infection control. Vancomycin resistantE. faecium(VREfm) is among the leading causes of hospital-acquired infections. VREfm may be exposed to chlorhexidine at supra- and subinhibitory concentrations as a result of chlorhexidine bathing and chlorhexidine-impregnated central venous catheter use. We used RNA sequencing to investigate how VREfm responds to chlorhexidine gluconate exposure. Among the 35 genes upregulated >=10 fold after 15 min of exposure to the MIC of chlorhexidine gluconate were those encoding VanA-type vancomycin resistance (vanHAX) and those associated with reduced daptomycin susceptibility (liaXYZ). We confirmed thatvanAupregulation was not strain or species specific by querying other VanA-type VRE. VanB-type genes were not induced. ThevanHpromoter was found to be responsive to subinhibitory chlorhexidine gluconate in VREfm, as was production of the VanX protein. UsingvanHreporter experiments withBacillus subtilisand deletion analysis in VREfm, we found that this phenomenon is VanR dependent. Deletion ofvanRdid not result in increased chlorhexidine susceptibility, demonstrating thatvanHAXinduction is not protective against chlorhexidine. As expected, VanA type VRE is more susceptible to ceftriaxone in the presence of sub-MIC chlorhexidine. Unexpectedly, VREfm is also more susceptible to vancomycin in the presence of subinhibitory chlorhexidine, suggesting that chlorhexidine-induced gene expression changes lead to additional alterations in cell wall synthesis. We conclude that chlorhexidine induces expression of VanA-type vancomycin resistance genes and genes associated with daptomycin nonsusceptibility. Overall, our results indicate that the impacts of subinhibitory chlorhexidine exposure on hospital-associated pathogens should be further investigated in laboratory studies. PMID- 26810655 TI - Population Pharmacokinetic Assessment and Pharmacodynamic Implications of Pediatric Cefepime Dosing for Susceptible-Dose-Dependent Organisms. AB - The Clinical and Laboratory Standards Institute (CLSI) revised cefepime (CFP) breakpoints forEnterobacteriaceaein 2014, and MICs of 4 and 8 MUg/ml were reclassified as susceptible-dose dependent (SDD). Pediatric dosing to provide therapeutic concentrations against SDD organisms has not been defined. CFP pharmacokinetics (PK) data from published pediatric studies were analyzed. Population PK parameters were determined using NONMEM, and Monte Carlo simulation was performed to determine an appropriate CFP dosage regimen for SDD organisms in children. A total of 664 CFP plasma concentrations from 91 neonates, infants, and children were included in this analysis. The median patient age was 1.0 month (interquartile range [IQR], 0.2 to 11.2 months). Serum creatinine (SCR) and postmenstrual age (PMA) were covariates in the final PK model. Simulations indicated that CFP dosing at 50 mg/kg every 8 h (q8h) (as 0.5-h intravenous [i.v.] infusions) will maintain free-CFP concentrations in serum of >4 and 8 MUg/ml for >60% of the dose interval in 87.1% and 68.6% of pediatric patients (age, >=30 days), respectively, and extending the i.v. infusion duration to 3 h results in 92.3% of patients with free-CFP levels above 8 MUg/ml for >60% of the dose interval. CFP clearance (CL) is significantly correlated with PMA and SCR. A dose of 50 mg/kg of CFP every 8 to 12 h does not achieve adequate serum exposure for older children with serious infections caused by Gram-negative bacilli with a MIC of 8 MUg/ml. Prolonged i.v. infusions may be useful for this population. PMID- 26810656 TI - Ebselen, a Small-Molecule Capsid Inhibitor of HIV-1 Replication. AB - The human immunodeficiency virus type 1 (HIV-1) capsid plays crucial roles in HIV 1 replication and thus represents an excellent drug target. We developed a high throughput screening method based on a time-resolved fluorescence resonance energy transfer (HTS-TR-FRET) assay, using the C-terminal domain (CTD) of HIV-1 capsid to identify inhibitors of capsid dimerization. This assay was used to screen a library of pharmacologically active compounds, composed of 1,280in vivo active drugs, and identified ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], an organoselenium compound, as an inhibitor of HIV-1 capsid CTD dimerization. Nuclear magnetic resonance (NMR) spectroscopic analysis confirmed the direct interaction of ebselen with the HIV-1 capsid CTD and dimer dissociation when ebselen is in 2-fold molar excess. Electrospray ionization mass spectrometry revealed that ebselen covalently binds the HIV-1 capsid CTD, likely via a selenylsulfide linkage with Cys198 and Cys218. This compound presents anti-HIV activity in single and multiple rounds of infection in permissive cell lines as well as in primary peripheral blood mononuclear cells. Ebselen inhibits early viral postentry events of the HIV-1 life cycle by impairing the incoming capsid uncoating process. This compound also blocks infection of other retroviruses, such as Moloney murine leukemia virus and simian immunodeficiency virus, but displays no inhibitory activity against hepatitis C and influenza viruses. This study reports the use of TR-FRET screening to successfully identify a novel capsid inhibitor, ebselen, validating HIV-1 capsid as a promising target for drug development. PMID- 26810658 TI - A Highly Macrolide-Resistant Campylobacter jejuni Strain with Rare A2074T Mutations in 23S rRNA Genes. PMID- 26810657 TI - Fumarate-Mediated Persistence of Escherichia coli against Antibiotics. AB - Bacterial persisters are a small fraction of quiescent cells that survive in the presence of lethal concentrations of antibiotics. They can regrow to give rise to a new population that has the same vulnerability to the antibiotics as did the parental population. Although formation of bacterial persisters in the presence of various antibiotics has been documented, the molecular mechanisms by which these persisters tolerate the antibiotics are still controversial. We found that amplification of the fumarate reductase operon (FRD) inEscherichia coliled to a higher frequency of persister formation. The persister frequency ofE. coliwas increased when the cells contained elevated levels of intracellular fumarate. Genetic perturbations of the electron transport chain (ETC), a metabolite supplementation assay, and even the toxin-antitoxin-relatedhipA7mutation indicated that surplus fumarate markedly elevated theE. colipersister frequency. AnE. colistrain lacking succinate dehydrogenase (SDH), thereby showing a lower intracellular fumarate concentration, was killed ~1,000-fold more effectively than the wild-type strain in the stationary phase. It appears thatSDHandFRDrepresent a paired system that gives rise to and maintainsE. colipersisters by producing and utilizing fumarate, respectively. PMID- 26810660 TI - Camel exposure and knowledge about MERS-CoV among Australian Hajj pilgrims in 2014. PMID- 26810659 TI - Identification of EnvC and Its Cognate Amidases as Novel Determinants of Intrinsic Resistance to Cationic Antimicrobial Peptides. AB - Cationic antimicrobial peptides (CAMPs) are an essential part of the innate immune system. Some Gram-negative enteric pathogens, such asSalmonella enterica, show intrinsic resistance to CAMPs. However, the molecular basis of intrinsic resistance is poorly understood, largely due to a lack of information about the genes involved. In this study, using a microarray-based genomic technique, we screened the Keio collection of 3,985Escherichia colimutants for altered susceptibility to human neutrophil peptide 1 (HNP-1) and identifiedenvCandzapBas novel genetic determinants of intrinsic CAMP resistance. In CAMP killing assays, anE. coliDeltaenvCEcor DeltazapBEcmutant displayed a distinct profile of increased susceptibility to both LL-37 and HNP-1. Both mutants, however, displayed wild-type resistance to polymyxin B and human beta-defensin 3 (HBD3), suggesting that the intrinsic resistance mediated by EnvC or ZapB is specific to certain CAMPs. A correspondingSalmonellaDeltaenvCSemutant showed similarly increased CAMP susceptibility. TheenvCmutants of bothE. coliandS. entericadisplayed increased surface negativity and hydrophobicity, which partly explained the increased CAMP susceptibility. However, the DeltaenvCEcmutant, but not the DeltaenvCSemutant, was defective in outer membrane permeability, excluding this defect as a common factor contributing to the increased CAMP susceptibility. Animal experiments showed that theSalmonellaDeltaenvCSemutant had attenuated virulence. Taken together, our results indicate that the role ofenvCin intrinsic CAMP resistance is likely conserved among Gram-negative enteric bacteria, demonstrate the importance of intrinsic CAMP resistance for full virulence ofS. enterica, and provide insight into distinct mechanisms of action of CAMPs. PMID- 26810661 TI - Variability in optical properties of atmospheric aerosols and their frequency distribution over a mega city "New Delhi," India. AB - The role of atmospheric aerosols in climate and climate change is one of the largest uncertainties in understanding the present climate and in capability to predict future climate change. Due to this, the study of optical properties of atmospheric aerosols over a mega city "New Delhi" which is highly polluted and populated were conducted for two years long to see the aerosol loading and its seasonal variability using sun/sky radiometer data. Relatively higher mean aerosol optical depth (AOD) (0.90 +/- 0.38) at 500 nm and associated Angstrom exponent (AE) (0.82 +/- 0.35) for a pair of wavelength 400-870 nm is observed during the study period indicating highly turbid atmosphere throughout the year. Maximum AOD value is observed in the months of June and November while minimum is in transition months March and September. Apart from this, highest value of AOD (AE) value is observed in the post-monsoon [1.00 +/- 0.42 (1.02 +/- 0.16)] season followed by the winter [0.95 +/- 0.36 (1.02 +/- 0.20)] attributed to significance contribution of urban as well as biomass/crop residue burning aerosol which is further confirmed by aerosol type discrimination based on AOD vs AE. During the pre-monsoon season, mostly dust and mixed types aerosols are dominated. AODs value at shorter wavelength observed maximum in June and November while at longer wavelength maximum AOD is observed in June only. For the better understanding of seasonal aerosol modification process, the aerosol curvature effect is studied which show a strong seasonal dependency under a high turbid atmosphere, which are mainly associated with various emission sources. Five days air mass back trajectories were computed. They suggest different patterns of particle transport during the different seasons. Results suggest that mixtures of aerosols are present in the urban environment, which affect the regional air quality as well as climate. The present study will be very much useful to the modeler for validation of satellite data with observed data during estimation of radiative effect. PMID- 26810662 TI - Biodegradation of chlorimuron-ethyl and the associated degradation pathway by Rhodococcus sp. D310-1. AB - Chlorimuron-ethyl is a typical long-term residual sulfonylurea herbicide, and strategies for its removal have attracted increasing attention. Microbial degradation is considered the most acceptable dissipation method. In this study, we optimized the cultivation conditions (substrate concentration, pH, inoculum concentration, and temperature) of the chlorimuron-ethyl-degrading bacterium Rhodococcus sp. D310-1 using response surface methodology (RSM) to improve the biodegradation efficiency. A maximum biodegradation rate of 88.95 % was obtained. The Andrews model was used to describe the changes in the specific degradation rate as the substrate concentration increased. Chlorimuron-ethyl could be transformed with a maximum specific degradation rate (q max), half-saturation constant (K S), and inhibition constant (K i) of 0.4327 day(-1), 63.50045 mg L( 1), and 156.76666 mg L(-1), respectively. Eight biodegradation products (2-amino 4-chloro-6-methoxypyrimidine, ethyl 2-sulfamoyl benzoate, 2-sulfamoyl benzoic acid, o-benzoic sulfimide, 2-[[(4-chloro-6-methoxy-2-pyrimidinyl) carbamoyl] sulfamoyl] benzoic acid, ethyl 2-carbonyl sulfamoyl benzoate, ethyl 2 benzenesulfonyl isocyanate benzoate, and N,N-2(ethyl formate)benzene sulfonylurea) were identified, and three possible degradation pathways were proposed based on the results of high performance liquid chromatography HPLC, liquid chromatography tandem mass spectroscopy (LC-MS/MS), and Fourier transform infrared spectroscopy (FTIR) analyses and the relevant literature. This systematic study is the first to examine the chlorimuron-ethyl degradation pathways of the genus Rhodococcus. PMID- 26810663 TI - Cake properties in ultrafiltration of TiO2 fine particles combined with HA: in situ measurement of cake thickness by fluid dynamic gauging and CFD calculation of imposed shear stress for cake controlling. AB - In this study, the cake buildup of TiO2 fine particles in the presence of humid acid (HA) and cake layer controlling during ultrafiltration (UF) were investigated. Specifically, we measured the cake thickness using fluid dynamic gauging (FDG) method under various solution conditions, including TiO2 concentration (0.1-0.5 g/L), HA concentration (0-5 mg/L, total organic carbon (TOC)), and pH values (e.g., 4, 6 and 10), and calculated the shear stress distribution induced by stirring using computational fluid dynamics (CFD) to analyze the cake layer controlling conditions, including the operation flux (50 200 L m(-2) h(-1)) and TiO2 concentration (0.1-0.5 g/L). It was found that lower TiO2/HA concentration ratio could lead to exceedingly severe membrane fouling because of the formation of a relatively denser cake layer by filling the voids of cake layer with HA, and pH was essential for cake layer formation owing to the net repulsion between particles. Additionally, it was observed that shear stress was rewarding for mitigating cake growth under lower operation flux as a result of sufficient back-transport forces, and exhibited an excellent performance on cake layer controlling in lower TiO2 concentrations due to slight interaction forces on the vicinity of membrane. PMID- 26810664 TI - Sorption of pharmaceuticals and personal care products to polyethylene debris. AB - Presence of plastic debris in marine and freshwater ecosystems is increasingly reported. Previous research suggested plastic debris had a strong affiliation for many pollutants, such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and heavy metals. In this study, the sorption behavior of pharmaceuticals and personal care products (PPCPs), including carbamazepine (CBZ), 4-methylbenzylidene camphor (4MBC), triclosan (TCS), and 17alpha-ethinyl estradiol (EE2), to polyethylene (PE) debris (250 to 280 MUm) was investigated. The estimated linear sorption coefficients (K d) are 191.4, 311.5, 5140, and 53,225 L/kg for CBZ, EE2, TCS, and 4MBC, and are related to their hydrophobicities. Increase of salinity from 0.05 to 3.5 % did not affect the sorption of 4MBC, CBZ, and EE2 but enhanced the sorption of TCS, likely due to the salting-out effect. Increase of dissolved organic matter (DOM) content using Aldrich humic acid (HA) as a proxy reduced the sorption of 4MBC, EE2, and TCS, all of which show a relatively strong affiliation to HA. Results from this work suggest that microplastics may play an important role in the fate and transport of PPCPs, especially for those hydrophobic ones. PMID- 26810665 TI - Compositions and pollutant sources of haze in Beijing urban sites. AB - Haze from urban sites in Beijing was collected with a self-assembled electrostatic dust collector. The sizes and morphologies, thermal properties, and compositions of the particles in the haze were characterized by scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), and X-ray photoelectric spectroscopy (XPS), respectively. Based on these results, the causes and pollutant sources of the chemicals in the haze were analyzed, and some countermeasures were further advanced to reduce the related pollutant sources. Graphical abstract ?. PMID- 26810667 TI - Preparation of magnetic photocatalyst nanohybrid decorated by polyoxometalate for the degradation of a pharmaceutical pollutant under solar light. AB - Magnetic polyoxometalate nanohybrid was prepared by the surface modification of gamma-Fe2O3/SrCO3 nanoparticles with PW 12 O 40 (3 -) polyoxometalate (POM) anions. The results of Fourier transform infrared (FTIR) and energy-dispersive X ray (EDX) confirm the presence of POM on the surface of gamma-Fe2O3/SrCO3 nanoparticles. TEM results revealed the ellipsoid-like structure of nanohybrid which was 23 nm in length and 6 nm in width. The activity of the photocatalyst was investigated by the photocatalytic degradation of ibuprofen (IBP) in an aqueous solution under solar light. It was found that in comparison with the gamma-Fe2O3/SrCO3, the degradation of IBP after 2-h exposure to the solar light irradiation was significantly higher for POM-gamma-Fe2O3/SrCO3 nanohybrids. The degradation of IBP was enhanced by the addition of H2O2 to the air saturated solution, while the addition of NaHCO3 and isopropanol restricted the degradation process. In the presence of H2O2, the Fenton photocatalyst degradation under solar light irradiation led to relatively complete degradation of IBP. Furthermore, the photocatalytic activity and magnetization properties of this magnetic photocatalyst nanohybrid provide a promising solution for the degradation of water pollutants and photocatalyst recovery. Graphical Abstract Schematic illustration for preparation of POM-gamma-Fe2O3/SrCO3 nanohybrid and photocatalytic reaction of IBP on POM-gamma-Fe2O3/SrCO3 nanohybrid. PMID- 26810666 TI - Possible protective role of elderberry fruit lyophilizate against selected effects of cadmium and lead intoxication in Wistar rats. AB - The objective of this study was the investigation whether the administration of the elderberry fruit lyophilizate under exposure to cadmium(Cd) and (Pb) lead may protect against some effects of their toxic action in Wistar rats. Rats were fed with diets containing Cd (Cd 0.025 mg/kg b.m.) or Pb (Pb 0.025 mg /kg b.m.) with the addition of the freeze-dried elderberry fruits (BEF) in the amount of 5 %. BEF added to the diet with Cd significantly decreased the activity of AST and ALT compared to the rats fed with the control diet with Cd (C + Cd). Activity of glutathione peroxidase was significantly higher in the blood of rats fed with BEF diet compared with animals fed with BEF + Cd, BEF + Pb, and C + Pb diets. Addition of BEF to the diets with Cd or Pb significantly decreased the uric acid concentration compared to the level of this parameter in the serum of animals fed with control diets containing Cd or Pb. The level of the Cd significantly decreased in the livers of rodents fed with BEF + Cd diet as compared to the concentration of this metal in the livers of rats fed with C + Cd diet. Elderberry fruit lyophilizate did not protect against the increased concentration of Cd or Pb in kidneys and bones of experimental rats; however, it improved the function of livers and kidneys, especially of rats intoxicated with Cd. PMID- 26810669 TI - Epidemiology and molecular mechanisms of antifungal resistance in Candida and Aspergillus. AB - The significant increase in the use of antifungal agents, both for the treatment of candidiasis and invasive aspergillosis and as azole fungicides in agricultural crop protection has resulted in the emergence of resistant clinical isolates, particularly to triazoles and echinocandins. Notably, among isolates that were primarily sensitive to fluconazole such as Candida parapsilosis and Candida tropicalis have witnessed an emerging resistance development. Also for echinocandins, the occurrence of Candida isolates with lower susceptibility to these drugs has been reported, which is possibly due to its broad clinical use. Triazole resistance among Aspergillus fumigatus and other Aspergillus species is commonly found in European and Asian countries. Specific mutations are associated with azole resistance in A. fumigatus and these mutations are now reported globally from six continents. Therefore, we highlight the need to conduct antifungal resistance surveillance studies using clinical isolates of Candida and Aspergillus in different geographical regions and monitoring of the infection rates in distinct population groups for early detection of resistance to these drugs and implementation of efficient policies for infection control and treatment. PMID- 26810668 TI - Oribatid communities and heavy metal bioaccumulation in selected species associated with lichens in a heavily contaminated habitat. AB - The study examines oribatid communities and heavy metal bioaccumulation in selected species associated with different microhabitats of a post-smelting dump, i.e. three lichen species of Cladonia with various growth forms and the slag substrate. The abundance of oribatids collected from the substrate was significantly lower than observed in lichen thalli. The morphology and chemical properties of lichens, and to some extent varying concentrations of heavy metals in thalli, are probably responsible for significant differences in oribatid communities inhabiting different Cladonia species. Some oribatids demonstrate the ability to accumulate zinc and cadmium with unusual efficiency, whereas lead is the most effectively regulated element by all species. A positive correlation was found between Zn content in all studied oribatids and their microhabitats. Oribatids exploring different food resources, i.e. fungivorous and non fungivorous grazers, show considerable differences in bioconcentrations of certain elements. PMID- 26810673 TI - Is a fractured skull discovered in the neonate after caesarean section delivery always evidence of negligence? PMID- 26810674 TI - Vitamin B12 and folate status in early pregnancy and cardiometabolic risk factors in the offspring at age 5-6 years: findings from the ABCD multi-ethnic birth cohort. AB - OBJECTIVE: To explore whether maternal vitamin B12 and folate status during early pregnancy are associated with cardiometabolic risk factors in the offspring at age 5-6. DESIGN: Prospective multi-ethnic birth cohort, the Amsterdam Born Children and their Development study (ABCD). SETTING: 12,373 pregnant women living in Amsterdam were approached between 2003 and 2004 for participation in the study. POPULATION: Mother-child pairs for whom information on maternal vitamin B12 or folate status in early gestation and health at age 5-6 years was available (n = 1950). METHODS: Vitamin B12 and folate concentrations were determined in maternal serum at intake in early pregnancy (median 13 weeks' gestation). Anthropometric measurements, blood pressure and fasting blood samples were collected during a health check of children aged 5-6 years. Multiple linear regression was performed to investigate the association between maternal serum concentrations and children's outcomes, corrected for confounders. MAIN OUTCOME MEASURES: Gestational age at birth, birthweight, body mass index (BMI), glucose levels, triglyceride levels, blood pressure and heart rate of the offspring at age 5-6. RESULTS: Low maternal folate levels during early pregnancy were associated with slightly higher BMI in the offspring [decrease per 10 units: beta 0.07 kg/m(2), 95% confidence interval (CI) 0.01, 0.13]. Low maternal vitamin B12 concentrations were associated with higher heart rates (decrease per 100 units: beta 0.49 beats/min, 95% CI 0.11, 0.87). CONCLUSION: This study provides further evidence that maternal nutrition in early pregnancy may possibly program cardiometabolic health of the offspring. TWEETABLE ABSTRACT: Low folate and vitamin B12 levels during pregnancy are associated with higher BMI and heart rate in offspring. PMID- 26810675 TI - Folic acid in pregnancy. PMID- 26810670 TI - Racial discrimination, socioeconomic position, and illicit drug use among US Blacks. AB - PURPOSE: We assessed the relationship of self-reported racial discrimination with illicit drug use among US Blacks, and whether this differed by socioeconomic position (SEP). METHODS: Among 6587 Black participants in Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (2004-2005), we used multiple logistic regression models to test the association between racial discrimination (measured on the 6-item Experiences of Discrimination scale) and past-year illicit drug use, and whether this differed by SEP. RESULTS: Racial discrimination was associated with past-year drug use [adjusted odds ratio (aOR) 2.32; 95 % confidence interval (CI) 1.70, 3.16] and with frequent drug use (aOR 1.91; 95 % CI 1.22, 2.99). For frequent illicit drug use, this relationship was stronger among higher SEP participants (aOR 3.55; 95 % CI 2.09, 6.02; p interaction < 0.01). CONCLUSIONS: The stronger association between racial discrimination and frequent illicit drug use among higher SEP Blacks suggests a complex interplay between disadvantaged and privileged statuses that merits further investigation. The finding of a significant difference by SEP highlights the importance of considering differences within heterogeneous race/ethnic groups when investigating health disparities. PMID- 26810676 TI - Caesarean deliveries: what has changed over the last century? PMID- 26810677 TI - The age of cervical screening should be reduced: AGAINST: The required evidence does not exist. PMID- 26810678 TI - The age of cervical screening should be reduced: FOR: Invite them all by 25; use clinical judgement rather than refusing them below that age. PMID- 26810679 TI - Opportunistic bilateral salpingectomy (OBS) for the prevention of ovarian cancer should be offered in the context of a clinical trial: FOR: There is lack of clarity on a number of key issues. PMID- 26810680 TI - Opportunistic salpingectomy at benign gynaecological surgery for ovarian cancer prevention should be performed within a clinical trial: AGAINST: Can we afford to wait for the results? PMID- 26810681 TI - What is the acceptable decision-to-delivery interval for an emergency caesarean section? PMID- 26810682 TI - Re: An observational study of the success and complications of 2546 external cephalic versions in low-risk pregnancies performed by trained midwives. PMID- 26810683 TI - Re: The changing practice of the obstetrician. PMID- 26810684 TI - Authors' reply re: An observational study of the success and complications of 2546 external cephalic versions in low-risk pregnant women performed by trained midwives. PMID- 26810685 TI - Re: Reappraisal of endometrial thickness for the detection of endometrial cancer in postmenopausal bleeding: a retrospective cohort study. PMID- 26810686 TI - Authors' reply re: Reappraisal of endometrial thickness for the detection of endometrial cancer in postmenopausal bleeding: a retrospective cohort study. PMID- 26810690 TI - In vitro potential modulation of baicalin and baicalein on P-glycoprotein activity and expression in Caco-2 cells and rat gut sacs. AB - Context Previous studies have shown that Scutellariae Radix, the dried root of Scutellaria baicalensis Georgi (Labiatae), has a certain inhibitory effect on P glycoprotein (P-gp), but the effects of its main active constituents on P-gp are still ambiguous. Objectives In vitro studies were performed to investigate the effects of its main active constituents (baicalin and its aglycone, baicalein) on the activity and expression of P-gp in intestine using Caco-2 cells and rat gut sacs. Materials and methods In Caco-2 cell experiments, the effects of baicalin and baicalein on P-gp activity were investigated using a P-gp substrate, rhodamine 123 and non-substrate fluorescein Na, by determining their intracellular fluorescence accumulation, and their effects on P-gp expression were determined using flow cytometry. In addition, rat gut sac model was selected to investigate the effects of baicalin and baicalein on the transport of verapamil, a classical P-gp substrate. The gut sacs of male Sprague-Dawley rats were filled with 0.4 mL the test solution contained verapamil (0.2575 mg/mL) and the drugs [baicalin and baicalein, at concentrations of 1/8 IC50 (59.875, 41.5 MUg/mL), 1/4 IC50 (119.75, 83 MUg/mL) and 1/2 IC50 (239.5, 166 MUg/mL)], and then incubated in Tyrode's solution for a period of time. After termination of the incubation, the incubated solution was processed for the subsequent detection. Results According to the results of MTT assay, the IC50 values of verapamil, baicalin and baicalein were 104, 479, 332 MUg/mL, respectively. The obtained results from the two models were confirmed mutually. As a result, baicalin exhibited no obvious effect on intracellular accumulation of Rh-123, and almost had no effect on P-gp expression and verapamil transportation, while baicalein significantly increased intracellular accumulation of Rh-123 (p < 0.01), down regulated P-gp expression (p < 0.01) and increased the transport of verapamil (p < 0.05). Discussion and conclusion The results indicated that baicalein may be a P-gp inhibitor, which presented obvious inhibitory effects on P-gp activity and expression level. A comparison of the structures of baicalin and baicalein indicates that the existence of glucosyl plays a decisive role in influencing the activity and expression of P-gp. PMID- 26810689 TI - Tick-Borne Encephalitis sequelae at long-term follow-up: a self-reported case control study. AB - BACKGROUND: Tick-borne encephalitis (TBE), caused by the TBE virus (TBEV), is a major neurotropic infection throughout Europe and Asia, with a considerable risk of neurological sequelae. Our aim was to study the symptoms in patients with TBE in Western Gotaland between 1997 and 2012 in the acute phase and at follow-up after 2-15 years (median: 5.5 years). METHODS: The medical records of 96 patients with TBE were studied. Phone-based interviews were held with 92 patients and 58 controls, matched by age, gender and residential area. The Encephalitis Support Group Questionnaire (ESGQ) 2000 was used, further developed with dimensions and scoring 1-4, where a high score is related to better outcome. Patients and controls also answered a written survey regarding functional outcome of sleep (FOSQ). RESULTS: Of the patients, 35% had a mild disease, 56% moderate and 7.3% severe disease. At the follow-up, patients scored significantly lower than controls in the dimensions of memory/learning, executive functions, vigilance and physical impairments. In addition, the answers concerning tiredness/fatigue, poor concentration/attention, reduced initiative/motivation, balance disturbances, coordination problems, difficulties with short- and long-term memory, learning difficulties and problems with fine motor skills resulted in significantly lower scores in the patients compared with the controls. The patients scored lower than the controls in the FOSQ dimension social outcome. CONCLUSIONS: At the long-term follow-up, the patients scored significantly lower in a diversity of neurocognitive and motor symptoms, in comparison with controls. These sequelae and their pathogenesis should be further explored and specific neurocognitive assessment tests are needed. PMID- 26810691 TI - Commentary: Toward the Next Generation of Home Visiting Programs--New Developments and Promising Directions. PMID- 26810692 TI - Punjab's minister of medical education moves to oust medical council president. PMID- 26810693 TI - Political interference derails Punjab Medical Council's investigation into "ghost faculty". PMID- 26810694 TI - On the horizon: trophic peptide growth factors as therapy for neonatal short bowel syndrome. AB - INTRODUCTION: Short bowel syndrome (SBS) occurs more commonly in human neonates than in adults. There are currently no approved therapeutic agents aimed directly at stimulating intestinal adaptation in this population. AREAS COVERED: A brief review of SBS and intestinal adaptation is first presented. We then present candidate peptide growth factors that are suggested to augment intestinal adaptation in SBS, with a particular focus on glucagon-like peptide-2, as well as insulin-like growth factor-1 and epidermal growth factor. The normal physiology of these peptides and our understanding of their roles in intestinal adaptation are discussed. We further consider the roles of these peptides in the ontogeny of the gastrointestinal tract and we present the limited preclinical data on the effects of administering these peptides in neonatal SBS. EXPERT OPINION: The clinical translation of trophic peptide therapies in neonatal SBS will require several challenges to be overcome. The optimal dose, timing and route of administration for the likely peptide, or combination of peptides, to be administered will be paramount. Despite their cost to patient care, trophic peptides have shown promise in preclinical models of neonatal SBS and may be especially beneficial for neonates that lack remnant ileum and suffer from irreversible intestinal failure. PMID- 26810696 TI - 3D printed guides for controlled alignment in biomechanics tests. AB - The bone-machine interface is a vital first step for biomechanical testing. It remains challenging to restore the original alignment of the specimen with respect to the test setup. To overcome this issue, we developed a methodology based on virtual planning and 3D printing. In this paper, the methodology is outlined and a proof of concept is presented based on a series of cadaveric tests performed on our knee simulator. The tests described in this paper reached an accuracy within 3-4 degrees and 3-4mm with respect to the virtual planning. It is however the authors' belief that the method has the potential to achieve an accuracy within one degree and one millimeter. Therefore, this approach can aid in reducing the imprecisions in biomechanical tests (e.g. knee simulator tests for evaluating knee kinematics) and improve the consistency of the bone-machine interface. PMID- 26810698 TI - Flexible and Adhesive Surface Enhance Raman Scattering Active Tape for Rapid Detection of Pesticide Residues in Fruits and Vegetables. AB - The efficient extraction of targets from complex surfaces is vital for technological applications ranging from environmental pollutant monitoring to analysis of explosive traces and pesticide residues. In our present study, we proposed a proof-of-concept surface enhance Raman scattering (SERS) active substrate serving directly to the rapid extraction and detection of target molecules. The novel substrate was constructed by decorating the commercial tape with colloidal gold nanoparticles (Au NPs), which simultaneously provides SERS activity and "sticky" of adhesive. The utility of SERS tape was demonstrated by directly extracting pesticide residues in fruits and vegetables via a simple and viable "paste and peel off" approach. The obtained strong and easily distinguishable SERS signals allow us to detect various pesticide residues such as parathion-methyl, thiram, and chlorpyrifos in the real samples with complex surfaces including green vegetable, cucumber, orange, and apple. PMID- 26810699 TI - Sponsorship of paediatricians/paediatric societies by the Baby Feeding Industry- a position paper by the International Society for Social Paediatrics and Child Health. PMID- 26810703 TI - The morpholino molecular beacon for specific RNA visualization in vivo. AB - A non-invasive fluorescent probe, morpholino molecular beacon (MO-MB), was designed for RNA visualization in vivo. Featuring negligible toxicity, stability, and high target specificity in living embryos, MO-MB is superior to conventional probes and has the potential for specific RNA visualization in basic biological and clinical research. PMID- 26810702 TI - Uncertainty is associated with increased selective attention and sustained stimulus processing. AB - Uncertainty about future threat has been found to be associated with an overestimation of threat probability and is hypothesized to elicit additional allocation of attention. We used event-related potentials to examine uncertainty related dynamics in attentional allocation, exploiting brain potentials' high temporal resolution and sensitivity to attention. Thirty participants performed a picture-viewing task in which cues indicated the subsequent picture valence. A certain-neutral and a certain-aversive cue accurately predicted subsequent picture valence, whereas an uncertain cue did not. Participants overestimated the effective frequency of aversive pictures following the uncertain cue, both during and after the task, signifying expectancy and covariation biases, and they tended to express lower subjective valences for aversive pictures presented after the uncertain cue. Pictures elicited increased P2 and LPP amplitudes when their valence could not be predicted from the cue. For the LPP, this effect was more pronounced in response to neutral pictures. Uncertainty appears to enhance the engagement of early phasic and sustained attention for uncertainly cued targets. Thus, defensive motivation related to uncertainty about future threat elicits specific attentional dynamics implicating prioritization at various processing stages, especially for nonthreatening stimuli that tend to violate expectations. PMID- 26810704 TI - AuO: Evolving from Dis- to Comproportionation and Back Again. AB - The structural, electronic, and dynamic properties of hypothetical gold(II) oxide (AuO) are studied theoretically, at atmospheric and elevated pressures, with the use of hybrid density functional theory. At p = 1 atm, hypothetical AuO (metastable with respect to the elements) is predicted to crystallize in a new structure type, unique among the late-transition-metal monoxides, with disproportionation of the Au ions to Au(I/III) and featuring aurophilic interactions. Under pressure, familiar structure types are stabilized: a semiconducting AgO-type structure at ~2.5 GPa and, with a further increase of the pressure up to ~80 GPa, an AuSO4-type structure containing Au2 pairs. Finally, above 105 GPa, distorted NaCl- and CsCl-type Au(II)O structures dominate, and metallization is predicted at 329 GPa. PMID- 26810705 TI - Palladium-catalyzed direct C-H arylation of pyridine N-oxides with potassium aryl and heteroaryltrifluoroborates. AB - An efficient ligand-free Pd(OAc)2-catalyzed selective arylation of pyridine N oxides using potassium (hetero)aryltrifluoroborates as coupling partners via C-H bond activation was achieved in the presence of TBAI. This approach has a broad substrate scope and shows moderate to high yields. PMID- 26810707 TI - Pulmonary vein anatomy assessed by cardiac magnetic resonance imaging in patients undergoing initial atrial fibrillation ablation: implications for novel ablation technologies. AB - BACKGROUND: Novel atrial fibrillation (AF) ablation tools have been designed to facilitate "single-shot" pulmonary vein (PV) isolation using multi-electrode or balloon-based catheters. However, in contrast to point-by-point radiofrequency ablation, these tools may be more dependent on suitable PV anatomy to achieve circumferential PV isolation. METHODS: Three hundred and twenty-two patients underwent gadolinium-enhanced cardiac magnetic resonance angiography to delineate PV anatomy prior to initial AF ablation. Long (a) and short (b) axis measurements of the PV orifice were used to calculate the eccentricity index of the PV ostium. RESULTS: Long axis dimensions of the left superior PV were 18.2 +/- 3.3 mm, left inferior PV 17.7 +/- 3.9 mm, right superior PV (RSPV) 20.4 +/- 4.3, and right inferior PV 18.7 +/- 4.7 mm. The long axis dimension of the RSPV was significantly larger than other PVs (p < 0.001). Forty-two patients (13 %) had at least one PV with a long axis dimension >25 mm and 16 patients (5 %) had at least one PV with a long axis dimension >28 mm. Left-sided PV ostia were significantly more ellipse-shaped than the right-sided PVs, which tended to be more spherical. A significant positive correlation was noted between increasing PV size and increased orifice eccentricity. CONCLUSIONS: In this large cohort undergoing initial AF ablation, over 10 % of patients had at least one standard PV with a dimension >25 mm. Additionally, significant differences were noted between left- and right-sided veins with regard to orifice eccentricity. These findings have implications for the design of AF ablation tools and may account for differential isolation rates between PVs noted in some recent studies of novel ablation technologies. PMID- 26810709 TI - A spectroscopic study of substituted anthranilic acids as sensitive environmental probes for detecting cancer cells. AB - Small-molecule fluorescent reporters of disease states are highly sought after, yet they remain elusive. Anthranilic acids are extremely sensitive environmental probes, and hold promise as general but selective agents for cancer-cell detection if they can be equipped with the appropriate targeting groups. The optical properties of a small library of N-isopropyl invariant anthranilic acids were investigated in methanol and chloroform. Points of variation included: fluoro, trifluoromethyl, or cyano substitution on the aromatic ring, and derivitization of the parent carboxylic acid as esters or secondary carboxamides. Phenylboronic acid conjugation at the carboxylic acid alongside un-, mono-, and dimethylated 2-amino groups was also explored. The boron-containing anthranilic acids were also evaluated as sensitive fluorescent probes for cancer cells using laser scanning confocal microscopy. In general, the compounds produced blue fluorescence that was strongly influenced by substitution and environment. 4 Trifluoromethyl and 4-cyano esters proved to be the most sensitive environmental probes with quantum yields as large as 100% in chloroform, and enhancements of up to 30-fold on going from methanol to chloroform. Stokes shifts ranged from 63 to 120nm, generally increasing with ortho-substitution and environmental polarity. It was demonstrated that phenylboronic acid conjugation was an attractive method for cancer cell detection via boronate ester formation with overexpressed glycoproteins (with no interference from normal, healthy cells), presumably due to favorable boron-sialic acid interactions. PMID- 26810710 TI - A novel library of saccharin and acesulfame derivatives as potent and selective inhibitors of carbonic anhydrase IX and XII isoforms. AB - Small libraries of N-substituted saccharin and N-/O-substituted acesulfame derivatives were synthesized and tested as atypical and selective inhibitors of four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). Most of them inhibited hCA XII in the low nanomolar range, hCA IX with KIs ranging between 19 and 2482nM, whereas they were poorly active against hCA II (KIs >10MUM) and hCA I (KIs ranging between 318nM and 50MUM). Since hCA I and II are ubiquitous off-target isoforms, whereas the cancer-related isoforms hCA IX and XII were recently validated as drug targets, these results represent an encouraging achievement in the development of new anticancer candidates. Moreover, the lack of a classical zinc binding group in the structure of these inhibitors opens innovative, yet unexplored scenarios for different mechanisms of inhibition that could explain the high inhibitory selectivity. A computational approach has been carried out to further rationalize the biological data and to characterize the binding mode of some of these inhibitors. PMID- 26810711 TI - Fluorinated matrix metalloproteinases inhibitors--Phosphonate based potential probes for positron emission tomography. AB - Fluorine-containing inhibitors of matrix metalloproteinases (MMPs) can serve as lead structures for the development of (18)F-labeled radioligands. These compounds might be useful as non-invasive imaging probes to characterize pathologies associated with increased MMP activity. Results with a series of fluorinated analogs of a known biphenyl sulfonamide inhibitor have shown that fluorine can be incorporated into two different positions of the molecular scaffold without significant loss of potency in the nanomolar range. Additionally, the potential of a hitherto unknown fluorinated tertiary sulfonamide as MMP inhibitor has been demonstrated. PMID- 26810712 TI - Design, synthesis, and docking studies of phenylpicolinamide derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety as c-Met inhibitors. AB - Four series of phenylpicolinamide derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety (12a-e, 13a-f, 14a-f and 15a-i) were designed, synthesized and evaluated for the IC50 values against three cancer cell lines (A549, PC-3 and MCF-7) and c Met kinase. Five selected compounds (13b, 15b, 15d, 15e and 15f) were further evaluated for the activity against HepG2 and Hela cell lines. Eighteen of the compounds showed excellent cytotoxicity activity and selectivity with the IC50 valuables in single-digit MUM to nanomole range. Seven of them are equal to more active than positive control Foretinib against one or more cell lines. The most promising compound 15f showed superior activity to Foretinib, with the IC50 values of 1.04+/-0.11MUM, 0.02+/-0.01MUM and 9.11+/-0.55MUM against A549, PC-3 and MCF-7 cell lines, which were 0.62 to 19.5 times more active than Foretinib (IC50 values: 0.64+/-0.26MUM, 0.39+/-0.11MUM, 9.47+/-0.22MUM), respectively. Structure-activity relationships (SARs) and docking studies indicated that replacement of quinoline nucleus of the previous active compounds with 1H pyrrolo[2,3-b]pyridine moiety maintained even improved the potent cytotoxic activity. The results suggested that the introduction of fluoro atoms to the aminophenoxy part of target compounds or the phenyl group of pyrimidine substituted on C-4 position was benefit for the activity. PMID- 26810713 TI - The Diagnostic Guideline for Anxiety and Challenging Behaviour for Persons with Intellectual Disabilities: Preliminary Outcomes on Internalizing Problems, Challenging Behaviours, Quality of Life and Clients' Satisfaction. AB - BACKGROUND: People with intellectual disabilities are vulnerable to develop psychopathology (in particular anxiety) and related challenging behaviour. A diagnostic guideline was developed to support professionals to better diagnose and thus treat psychopathology and related CB. This study examined preliminary outcomes from the application of this guideline. METHOD: A comparative multiple case study with an experimental and a control condition. RESULTS: The application of the guideline showed a trend of decreases of internalizing problems (P = 0.07) and anxiety/depressed problems (P = 0.09). We found no statistically significant decreases of externalizing problems and no increases in perceived quality of life as compared with care as usual. Clients were not more satisfied with the support they received for coping with their emotional and behaviour problems. CONCLUSION: The application of the Diagnostic Guideline for Anxiety and Challenging Behaviour did not show statistically significant changes in externalizing problems and Quality of Life. Despite the small sample size of n = 59, we did find a trend in decreasing internalizing problems and anxiety/depressed problems. Further research into either or not confirming these trends is recommended. PMID- 26810714 TI - Increased Computed Tomography Dose Due to Miscentering With Use of Automated Tube Voltage Selection: Phantom and Patient Study. AB - The purpose of the article is to determine if miscentering affected dose with use of automated tube voltage selection software. An anthropomorphic phantom was imaged at different table heights (centered in the computed tomography [CT] gantry, and -6, -3, +3, and +5.7cm relative to the centered position). Topogram magnification, tube voltage selection, and dose were assessed. Effect of table height on dose also was assessed retrospectively in human subjects (n = 50). When the CT table was positioned closer to the x-ray source, subjects appeared up to 33% magnified in topogram images. When subjects appeared magnified in topogram images, automated software selected higher tube potentials and tube currents that were based on the magnified size of the subject rather than the subject's true size. Table height strongly correlated with CT dose index (r = 0.98, P < 0.05) and dose length product (r = 0.98, P < 0.05) in the phantom study. Transverse dimension in the topogram highly correlated with dose in human subjects (r = 0.75 0.87, P <0.05). Miscentering results in increased dose due to topogram magnification with automated voltage selection software. PMID- 26810715 TI - Osteosynthesis in sacral fracture and lumbosacral dislocation. AB - Sacral fracture and lumbosacral hinge trauma are rare but serious lesions. Neurologic disorder is frequently associated, and nerve release may be required, with reduction and stabilization of the fracture. Management requires knowing the fracture lines and reduction maneuvers and the fixation techniques that may need to be associated. Three classifications allow these fractures to be well understood: the Roy-Camille classification identifies high transverse fractures and their displacement; the Denis classification identifies vertical fracture line location within the sacrum, which correlates with neurologic risk; and the Tile classification analyzes pelvic ring trauma when associated with the sacral fracture. Treatment, when surgical, requires careful patient positioning, sometimes on an orthopedic table. Reduction maneuvers are founded on the fracture classification. Isolated U-shaped fracture of the sacrum is to be distinguished from sacral fracture associated with pelvic ring lesion. Osteosynthesis may be lumbopelvic or restricted to the pelvic ring (sacroiliac or iliosacral). Open osteosynthesis allows reduction to be finalized by intraoperative maneuvers on the implant, while closed osteosynthesis requires perfect preoperative reduction. Complications are frequent and neurologic recovery is uncertain. Fatigue and osteoporotic fractures show little displacement and are good indications for cementoplasty, either isolated or associated to iliosacral screwing. In lumbosacral hinge trauma, and dislocation in particular, reduction surgery with fixation (usually 360 degrees ) is indicated. The present study details the analysis and classification of these fractures, the technical pitfalls of reduction and fixation, and treatment indications. PMID- 26810716 TI - Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production. AB - BACKGROUND: Subcutaneous allergen-specific immunotherapy is a standard route for the immunotherapy of allergic diseases. It modulates the course of allergy and can generate long-term remission. However, subcutaneous allergen-specific immunotherapy can also induce anaphylaxis in some patients, and therefore additional routes of administration should be investigated to improve the safety and tolerability of immunotherapy. OBJECTIVE: We sought to determine whether epicutaneous treatment with antigen in the presence of a Toll-like receptor 9 agonist can suppress TH2-mediated responses in an antigen-specific manner. METHODS: Epicutaneous immunization was performed by applying a skin patch soaked with ovalbumin (OVA) plus CpG, and its suppressor activity was determined by using the mouse model of atopic dermatitis. Finally, adoptive cell transfers were implemented to characterize the regulatory cells that are induced by epicutaneous immunization. RESULTS: Epicutaneous immunization with OVA and CpG reduces the production of OVA-specific IgE and increases the synthesis of OVA-specific IgG2a antibodies in an antigen-specific manner. Moreover, eosinophil peroxidase activity in the skin and production of IL-4, IL-5, IL-10, and IL-13 are suppressed. The observed reduction of IgE synthesis is transferable with T-cell receptor (TCR) alphabeta(+)CD4(+)CD25(-) cells, whereas IgG2a production is dependent on both TCRalphabeta(+) and TCRgammadelta(+) T cells. Further experiments show that the described phenomenon is myeloid differentiation primary response 88, IFN-gamma, and IL-17A dependent. Finally, the results suggest that epicutaneous immunization with OVA and CpG decreases the synthesis of OVA specific IgE and skin eosinophil peroxidase activity in mice with ongoing skin allergy. CONCLUSION: Epicutaneous application of protein antigen in the presence of adjuvant could be an attractive needle-free and self-administered immunotherapy for allergic diseases. PMID- 26810717 TI - Analysis of nocebo effects of antiepileptic drugs across different conditions. AB - The aim of this study was to assess the nocebo effect in all randomised controlled trials (RCTs) exploring the effect of antiepileptic drugs (AEDs) in the clinical conditions in which these compounds have been studied with the exception of epilepsy. We searched for all double-blind, placebo-controlled trials performed in adult patients, testing AEDs in any clinical condition except epilepsy. The following data were extracted from the placebo arms: the number of randomized patients, the number of patients withdrawing because of adverse effects (AEs), and the number of patients with 11 predefined AEs (dizziness, ataxia/coordination abnormal, diplopia, somnolence, fatigue, headache, memory impairment, tremor, abnormal thinking, anxiety and depression). Outcome measures were the percentages of patients whithdrawing due to AEs and reporting the selected AEs. RCTs included in the analysis were grouped in six main categories of clinical conditions (pain, movement disorders, psychiatric disorders, substance abuse, obesity and binge eating disorders, and miscellanea). Proportions of patients with 95 % confidence intervals (CIs) have been calculated for all reported outcome measures. Thirteen AEDs were studied and the total number of selected RCTs was 157. Significant percentages of placebo-treated patients withdrawing due to AEs and with specific AEs were observed in several cases. Significant differences emerged across different conditions. Comparisons with results of a previous meta-analysis on all RCTs in patients with drug resistant epilepsies showed that ataxia, diplopia and fatigue were significantly more frequent, and patients withdrawing were significantly less frequent, in placebo-treated epileptic patients. Significant differences have been identified in the AEDs-induced nocebo effect across different conditions. Placebo-treated epilepsy patients have significantly more frequent neurological AEs. PMID- 26810720 TI - Luigi Calori (1807-1896). PMID- 26810719 TI - Atypical parkinsonism in C9orf72 expansions: a case report and systematic review of 45 cases from the literature. AB - While C9orf72 repeat expansions usually present with frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS), an increasing number of reports suggests that the primary phenotype of C9orf72 patients may also include movement disorders. We here provide the first systematic clinical characterisation of C9orf72-associated parkinsonism. We report a C9orf72 expansion carrier presenting with a clinical syndrome of progressive supranuclear palsy (PSP), pronounced mesencephalic atrophy on MRI and PSP-characteristic electrooculography findings. Moreover, we systematically review all previous reports on C9orf72 patients with parkinsonian features. Review of 28 reports revealed 45 C9orf72-positive patients with hypokinesia, rigidity and/or resting tremor. C9orf72-associated parkinsonism predominantly consisted in a hypokinetic-rigid syndrome without resting tremor (61%), with both asymmetric (59%) and symmetric (41%) distributions. Additional features included upper motor neuron signs (60%), lower motor neuron signs (36%), cognitive dysfunction (85%), behaviour and/or personality change (55%) and psychiatric symptoms (29%). Vertical supranuclear gaze palsy was reported in three further cases and cerebellar dysfunction in four cases. Family history frequently yielded evidence of ALS (31%) and FTD (21%). Atypical parkinsonism is a recurrent phenotypic manifestation of C9orf72 expansions. It occurs as part of a broad spectrum of C9orf72-related multi-system neurodegeneration, which can include basal ganglia, mesencephalic and cerebellar dysfunction. C9orf72 genotyping should be considered in those patients with atypical parkinsonism who present with a family history of ALS or FTD, upper or lower motor neuron signs and/or cognitive dysfunction with pronounced frontotemporal impairment. PMID- 26810721 TI - Concomitant granule cell neuronopathy in patients with natalizumab-associated PML. AB - Granule cell neuronopathy (GCN) is a rare JC virus infection of the cerebellar granule cell neurons in immunocompromised patients. On brain imaging, GCN is characterized by cerebellar atrophy which can be accompanied by infratentorial white matter lesions. The objective of this study is to investigate the prevalence of MRI findings suggestive of GCN in a large natalizumab-associated progressive multifocal leukoencephalopathy (PML) cohort. MRI scans from before, at the time of, and during follow-up after diagnosis of PML in 44 natalizumab treated MS patients, and a control group of 25 natalizumab-treated non-PML MS patients were retrospectively reviewed for imaging findings suggestive of GCN. To assess and quantify the degree of cerebellar atrophy, we used a 4 grade rating scale. Three patients in the PML group showed imaging findings suggestive of GCN and none in the control group. In two of these PML patients, cerebellar atrophy progressed from grade 0 at the time of diagnosis of isolated supratentorial PML to grade 1 and 2 after 2.5 and 3 months, respectively, in the absence of infratentorial white mater lesions. The third patient had grade 1 cerebellar atrophy before diagnosis of infra- and supratentorial PML, and showed progression of cerebellar atrophy to grade 2 in the 3 months following PML diagnosis. None of the other eight patients with infratentorial PML lesions developed cerebellar atrophy suggestive of GCN. Three cases with imaging findings suggestive of GCN were detected among 44 natalizumab-associated PML patients. GCN may, therefore, be more common than previously considered in natalizumab-associated PML patients. PMID- 26810718 TI - Efficacy of glatiramer acetate in neuromyelitis optica spectrum disorder: a multicenter retrospective study. AB - Glatiramer acetate (GA) is an approved therapy for relapsing-remitting multiple sclerosis, but its efficacy for the prevention of attacks in neuromyelitis optica spectrum disorder (NMOSD) remains unknown. We did a multicenter retrospective analysis of GA-treated patients with NMOSD, identified through a national registry. Annualized relapse rate and expanded disability status scale (EDSS) were the main outcome measures. We identified 23 GA-treated patients (21 female, 16 aquaporin-4 antibody-positive). GA was given for <6 months in seven patients; reasons for stopping were relapses (n = 3), confirmation of NMOSD (n = 2) and side effects (n = 2). Of 16 patients treated >= 6 months with GA (15 female, 11 aquaporin-4 antibody-positive), 14 experienced at least one relapse. There was no reduction in the mean annualized relapse rate in the total group (1.9 +/- 1.1 before vs. 1.8 +/- 1.4 during GA therapy), as well as in those patients who were aquaporin-4 antibody-positive, or had a history of prior immunotherapy or not. The median EDSS increased (2.5 start vs. 3.5 finish of GA, P < 0.05). GA therapy was discontinued in 15/16 patients; reasons were therapeutic inefficacy in 13 and post-injection skin reactions in two patients. We conclude that GA is not beneficial for preventing attacks in most patients with NMOSD, particularly in aquaporin-4 antibody-positive cases. PMID- 26810722 TI - Early-onset progressive spastic paraplegia caused by a novel TUBB4A mutation: brain MRI and FDG-PET findings. PMID- 26810723 TI - Amnesia in frontotemporal dementia: shedding light on the Geneva historical data. AB - Recent accumulated evidence indicates that episodic memory impairments could be part of the initial clinical expression of frontotemporal dementia (FTD). An early study on this issue was carried out by Constantinidis and colleagues in 1974, but it was subsequently overlooked for a long period of time. The scope of the present research was: (a) to explore the presence of early episodic memory impairments in the entire population of neuropathologically confirmed FTD patients from the Geneva brain collection; and (b) to expand the present insight on the association between the initial symptomatology and various characteristics, namely gender, age at onset, disease duration, and presence of Pick body neuropathology. A careful review of the records of 50 FTD patients hospitalized at the Department of Psychiatry of the Bel-Air Hospital, Geneva, Switzerland, from 1929 to 1999, was conducted. Further in-depth neuropathological analysis with novel immunohistological methods was carried out in 37 of the cases. The data showed that memory impairments were the first clinical symptom in several of the patients. In addition, this specific phenotypic expression of FTD was associated with the female gender, advanced age, and positive Pick body neuropathology. The current findings give the opportunity to historically vindicate the early work of Constantinidis and colleagues. In addition, the novel observations about the association of episodic memory impairments with the female gender and positive Pick body neuropathology add to the existing knowledge about this phenotypic expression of FTD. PMID- 26810724 TI - Head-shaking nystagmus and vertigo cured by lateral semicircular canal occlusion. PMID- 26810726 TI - Lactose-free diet inducing aseptic pancreatitis and myoclonic jerks in late onset, putative MERRF syndrome. PMID- 26810725 TI - Thymic pathologies in myasthenia gravis: a preoperative assessment of CAT scan and nuclear based imaging. AB - Precise diagnostic work up of a suspected thymic pathology in patients with myasthenia gravis (MG) is very important for potential surgical implications and further disease course. In this study the diagnostic value of combined preoperative radiological (CAT scan) and nuclear based imaging (octreotide and thallium scintigraphy) in patients with MG was evaluated. Twenty four patients were included. Histopathology revealed thymoma in nine patients, thymic carcinoma (TC) in one patient, lymphofollicular hyperplasia in seven patients, and involuted thymus in another seven patients. Diagnostic sensitivity for detecting thymoma/TC was 80 % in CAT scan as well as in somatostatin scintigraphy; the combination of both procedures reached 90 %. However, the diagnostic specifity to exclude thymoma in CAT scan was 100 % and in octreotide scintigraphy 85.7 %. Semiquantitative octreotide uptake significantly correlated with histological grading of thymoma/TC (r = 0.764) and histological proliferation rate Ki67 (r = 0.894). Thallium scintigraphy was positive only in one out of four thymoma cases. In this study, somatostatin scintigraphy has been shown to be a useful additional diagnostic technique in detecting thymic malignancies in patients with MG. These results might be especially helpful in patients with late onset MG as these patients are in general no candidates for thymectomy. PMID- 26810727 TI - Screening of GNAL variants in Brazilian patients with isolated dystonia reveals a novel mutation with partial loss of function. AB - GNAL was identified as a cause of dystonia in patients from North America, Europe and Asia. In this study, we aimed to investigate the prevalence of GNAL variants in Brazilian patients with dystonia. Ninety-one patients with isolated idiopathic dystonia, negative for THAP1 and TOR1A mutations, were screened for GNAL variants by Sanger sequencing. Functional characterization of the Galphaolf protein variant was performed using the bioluminescence resonance energy transfer assay. A novel heterozygous nonsynonymous variant (p. F133L) was identified in a patient with cervical and laryngeal dystonia since the third decade of life, with no family history. This variant was not identified in healthy Brazilian controls and was not described in 63,000 exomas of the ExAC database. The F133L mutant exhibited significantly elevated levels of basal BRET and severely diminished amplitude of response elicited by dopamine, that both indicate substantial functional impairment of Galphaolf in transducing receptor signals, which could be involved in dystonia pathophysiology. GNAL mutations are not a common cause of dystonia in the Brazilian population and have a lower prevalence than THAP1 and TOR1A mutations. We present a novel variant that results in partial Galphaolf loss of function. PMID- 26810728 TI - The impact of regular lifestyle behavior in migraine: a prevalence case-referent study. AB - Regular lifestyle behaviors (RLBs) of sleep, exercise, mealtime pattern and hydration status independently affect migraine occurrence. We aimed herein to evaluate the differences in migraine occurrence among participants who do and do not maintain the RLB triumvirate. Cases of chronic migraine (CM) and referents of episodic migraine (EM) >= aged 15 years with charts regularly documenting RLB notes were continuously enrolled from a retrospective case-referent cohort study performed on electronic chart review from January 1, 2014 to January 1, 2015 at the Stanford Headache and Facial Pain Program. Association between RLB prevalence and migraine occurrence was studied. 175 CM and 175 EM patients were enrolled (mean age 44.4 years, 22 % males). Migraine was diagnosed according to the ICHD-3 beta criteria, and was confirmed by a Headache Specialist attending the Clinic. The CM cohort (22 %) exhibited less RLB than the EM cohort (69 %), with crude odds ratio of 0.13 (95 % confidence interval or CI 0.08-0.21). The adjusted odds ratio and adjusted relative risk between RLB+, Meds+ (those taking medication) and CM were 0.67 (95 % CI 0.32-1.40) and 0.74 (95 % CI 0.43-1.28), indicating no significant effect modification. Engaging in regular lifestyle behavior helps quell chronic migraine. PMID- 26810729 TI - Taste dysfunction in multiple sclerosis. AB - Empirical studies of taste function in multiple sclerosis (MS) are rare. Moreover, a detailed assessment of whether quantitative measures of taste function correlate with the punctate and patchy myelin-related lesions found throughout the CNS of MS patients has not been made. We administered a 96-trial test of sweet (sucrose), sour (citric acid), bitter (caffeine) and salty (NaCl) taste perception to the left and right anterior (CN VII) and posterior (CN IX) tongue regions of 73 MS patients and 73 matched controls. The number and volume of lesions were assessed using quantitative MRI in 52 brain regions of 63 of the MS patients. Taste identification scores were significantly lower in the MS patients for sucrose (p = 0.0002), citric acid (p = 0.0001), caffeine (p = 0.0372) and NaCl (p = 0.0004) and were present in both anterior and posterior tongue regions. The percent of MS patients with identification scores falling below the 5th percentile of controls was 15.07 % for caffeine, 21.9 % for citric acid, 24.66 % for sucrose, and 31.50 % for NaCl. Such scores were inversely correlated with lesion volumes in the temporal, medial frontal, and superior frontal lobes, and with the number of lesions in the left and right superior frontal lobes, right anterior cingulate gyrus, and left parietal operculum. Regardless of the subject group, women outperformed men on the taste measures. These findings indicate that a sizable number of MS patients exhibit taste deficits that are associated with MS-related lesions throughout the brain. PMID- 26810730 TI - New Records and Updated Checklist of Phlebotomine Sand Flies (Diptera: Psychodidae) From Liberia. AB - Phlebotomine sand flies from three counties in Liberia were collected from January 2011 to July 2013. In total, 3,118 sand flies were collected: 18 species were identified, 13 of which represented new records for Liberia. An updated taxonomic checklist is provided with a brief note on sand fly biology, and the disease vector potential for species is discussed. PMID- 26810731 TI - Pyrethroid Insecticide Resistance Mechanisms in the Adult Phlebotomus papatasi (Diptera: Psychodidae). AB - Phlebotomus papatasi is one of the most medically important sand fly species in the Old World, serving as a vector of Leishmania parasites and phleboviruses. Chemical control is still considered the most effective method for rapidly reducing populations of flying insects involved in vector-borne disease transmission, but is increasingly threatened by insecticide resistance in the target insect posing significant problems for entomologists responsible for control programs. This study was conducted to determine pyrethroid resistance mechanisms and the biological, physiological, and molecular impacts of resistance in Ph. papatasi, and to compare their resistance mechanisms against those reported for mosquitoes and other intensely studied dipterans. Field-collected Ph. papatasi from Aswan, Egypt, were subjected to sublethal doses of permethrin and reared as a resistant strain under laboratory conditions through 16 generations. Biological parameter observations of resistant Ph. papatasi revealed an association of resistance with productivity cost. Physiological analysis revealed that concentrations of oxidase and esterase enzymes increased in early generations of the resistant colony, and then subsided through the F16 generation to levels similar to those in a susceptible colony. The activity levels of acetylcholinesterase were higher in field-collected Ph. papatasi than in susceptible colony flies, but decreased significantly despite subsequent exposure to permethrin. The molecular search for gene mutations in the resistant strain of Ph. papatasi failed to identify any mutations common in pyrethroid-resistant mosquitoes. Our study revealed that the mechanism of pyrethroid resistance in sand flies is different than that in mosquitoes, at least at the genetic level. PMID- 26810732 TI - Pigmented villonodular synovitis diagnosed during revision total knee arthroplasty for flexion instability and patellar fracture. AB - Occurring in either a localized or diffuse form, pigmented villonodular synovitis (PVNS) is a disease of unknown etiology that typically presents with insidious onset of pain, swelling, stiffness, or mechanical symptoms as a result of synovial tissue proliferation. PVNS preferentially affects large joints, most commonly the knee. Currently there is no known association with PVNS and total knee arthroplasty (TKA), and to date, there are only a few cases reported in the orthopedic literature in which PVNS was diagnosed after primary TKA. To our knowledge, this is the first case of diffuse PVNS that was discovered at the time of revision TKA for flexion instability and patellar fracture. In this patient, with no known history of PVNS, the diagnosis of diffuse PVNS was made at the time of surgery. She underwent revision TKA, partial patellectomy, and extensive synovectomy. Level of evidence: V, Case Report. PMID- 26810735 TI - Development of a sliding mode control model for quiet upright stance. AB - Human upright stance appears maintained or controlled intermittently, through some combination of passive and active ankle torques, respectively representing intrinsic and contractile contributions of the ankle musculature. Several intermittent postural control models have been proposed, though it has been challenging to accurately represent actual kinematics and kinetics and to separately estimate passive and active ankle torque components. Here, a simplified single-segment, 2D (sagittal plane) sliding mode control model was developed for application to track kinematics and kinetics during upright stance. The model was implemented and evaluated using previous experimental data consisting of whole body angular kinematics and ankle torques. Tracking errors for the whole-body center-of-mass (COM) angle and angular velocity, as well as ankle torque, were all within ~10% of experimental values, though tracking performance for COM angular acceleration was substantially poorer. The model also enabled separate estimates of the contributions of passive and active ankle torques, with overall contributions estimated here to be 96% and 4% of the total ankle torque, respectively. Such a model may have future utility in understanding human postural control, though additional work is needed, such as expanding the model to multiple segments and to three dimensions. PMID- 26810736 TI - Risk of cancer among patients with depressive disorder: a meta-analysis and implications. AB - OBJECTIVE: The question of cancer risk in individuals with depression is unclear, primarily because of the heterogeneity of the assessment of depression in the published literature. To clarify the mixed findings, this analysis was limited to articles that used a reliable method of ascertaining depressive disorder. METHODS: We searched PubMed, EMBASE, and the Cochrane Library to identify studies investigating the effect of depression on subsequent risk of cancer, defining depression based on the criteria in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and/or the International Classification of Disease (ICD). We calculated a pooled odds ratio (OR) for developing cancer with the 95% confidence interval (CI). RESULTS: Nine studies fulfilled the eligibility criteria. In a random-effects model, patients with depressive disorder were at increased risk for cancer (OR, 1.26; 95% CI, 1.06-1.50, P = 0.01). However, a significant effect was observed only in low-quality studies (OR, 1.31; 95% CI, 1.05-1.63, P = 0.018), and not in high-quality studies (OR, 1.15; 95% CI, 0.85 1.56, P = 0.366). CONCLUSION: Our results did not demonstrate that people with depressive disorder are at increased risk for developing cancer. Well-designed prospective studies of recurrent or persistent depressive disorder that control for lifestyle factors including smoking are warranted. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26810733 TI - EBI-907, a novel BRAF(V600E) inhibitor, has potent oral anti-tumor activity and a broad kinase selectivity profile. AB - The oncogenic mutation of BRAF(V600E) has been found in approximately 8% of all human cancers, including more than 60% of melanoma and 10% of colorectal cancers. The clinical proof of concept in treating BRAF(V600E)-driving melanoma patients with the BRAF inhibitors has been well established. We have sought to identify and develop novel BRAF(V600E) inhibitors with more favorable profiles. Our chemistry effort has led to the discovery of EBI-907 as a novel BRAF(V600E) inhibitor with potent anti-tumor activity in vitro and in vivo. In a LanthaScreen BRAF(V600E) kinase assay, EBI-907 showed an IC50 of 4.8 nM, which is >10 -fold more potent than Vemurafenib (IC50 = 58.5 nM). In addition, EBI-907 showed a broader kinase selectivity profile, with potent activity against a number of important oncogenic kinases including FGFR1-3, RET, c-Kit, and PDGFRb. Concomitant with such properties, EBI-907 exhibits potent and selective cytotoxicity against a broader range of BRAF(V600E)-dependent cell lines including certain colorectal cancer cell lines with innate resistance to Vemurafenib. In BRAF(V600E)-dependent human Colo-205 and A375 tumor xenograft mouse models, EBI-907 caused a marked tumor regression in a dose-dependent manner, with superior efficacy to Vemurafenib. Our results also showed that combination with EGFR or MEK inhibitor enhanced the potency of EBI-907 in cell lines with innate or acquired resistance to BRAF inhibition alone. Our findings present EBI-907 as a potent and promising BRAF inhibitor, which might be useful in broader indications. PMID- 26810737 TI - Crystallographic insights into (CH3NH3)3(Bi2I9): a new lead-free hybrid organic inorganic material as a potential absorber for photovoltaics. AB - The crystal structure of a new bismuth-based light-absorbing material for the application in solar cells was determined by single crystal X-ray diffraction for the first time. (CH3NH3)3(Bi2I9) (MBI) is a promising alternative to recently rapidly progressing hybrid organic-inorganic perovskites due to the higher tolerance against water and low toxicity. Single crystal X-ray diffraction provides detailed structural information as an essential prerequisite to gain a fundamental understanding of structure property relationships, while powder diffraction studies demonstrate a high degree of crystallinity in thin films. PMID- 26810739 TI - The Structure Of The California Q-Set. AB - The study aim was to explore the dimensional structure of the California Q-Set, a widely use Q-sort procedure. The data analyzed consisted of the composited CQS descriptions of the male sample and the female sample during their high school years as reported by Block in his Lives Through Time. The 104 variables were intercorrelated across the 160 cases and analyzed by the method of principal components with a scree test criterion. The eight interpretable factors reported were rotated by the Promax procedure. The clear-cut simple structure was defined by 94 of the statements. The dimensions identified were found to resemble many behavioral rating factors reported for several inventories. PMID- 26810738 TI - The delivery of specialist spinal cord injury services in Queensland and the potential for telehealth. AB - BACKGROUND: The Queensland Spinal Cord Injuries Service (QSCIS) is a statewide service in Brisbane at the Princess Alexandra Hospital (PAH). The QSCIS assists individuals with a spinal cord injury (SCI) through three services: the Spinal Injuries Unit (SIU), Transitional Rehabilitation Program (TRP) and the Spinal Outreach Team (SPOT). The aim of this study was to undertake a review of ambulatory services provided by the QSCIS (SIU and SPOT) to help identify where telehealth may potentially be useful. METHODS: Profiling of patients with SCI in Queensland was achieved using database records containing referral data. Services provided by SIU Outpatient Clinics and the SPOT during a 6-year period (January 2008 - December 2013), were analysed. Using postcodes, we estimated distances between place of residence and Brisbane. We compared the general population of SCI patients with patients managed through SIU Outpatient Clinics and the SPOT. RESULTS: During the 6-year period, 2073 patients were referred to the QSCIS (and living) at the time of the analysis. 74% of all patients were male. The median age was 51y (IQR 39y-61y). About two-thirds of all patients lived within 200 km of Brisbane. 24% of all patients registered with the QSCIS lived further than 200 km away from Brisbane. 7513 appointments were provided in the SIU outpatient clinic. 43,827 occasions of service were reported by the SPOT, including telephone consultations (66%) and home visits (26%). 72 outreach clinics were held in selected regional sites for up to 100 patients per year. 13 videoconference appointments reported. 90% of all patients who attended the SIU outpatient clinic lived within 200 km of Brisbane. About two-thirds of patients who received a service from the SPOT lived within 200 km of Brisbane. CONCLUSION: Since one third of all patients registered with the QSCIS live at least 200 km away from Brisbane; it appears that these patients may not be accessing the same services as Brisbane based patients. Telehealth models of care, which promote better engagement with local health service providers (such as general practitioners, nurse practitioners and allied health professionals) could improve equity of access and reduce the need for extensive travel. PMID- 26810740 TI - Casey's Method For Fitting Hyperplanes From An Intermediate Orthomax Solution. AB - The loadings in the column vector representing a varimax factor are dichotomized into "large" and "small," in absolute value, as to whether they are larger than or equal to, in absolute value, or smaller than, in absolute value, the square of the mean of the square roots of their absolute values. The test vectors associated with the small loadings so designated are fitted to a hyperplane in the standard way, following Tucker. Accomplishing this for all varimax factor provides an oblique solution, of the hyperplane fitting variety, which may be said to correspond closely to the associated orthonormal varimax solution. The procedure, for convenience in reference, is called "Casey's Method." Four examples of the application of Casey's Method are provided. PMID- 26810741 TI - The Use Of Analysis Of Covariance Structures For Comparing The Psychometric Properties Of Multiple Variables Across Populations. AB - It is common practice to assume that the dependent variables in differential prediction studies, and analysis of variance and co-variance designs are characterized by certain psychometric properties which are invariant across the subgroups of interest. More specifically, the accuracy of the results of such analyses depends on the assumption that the dependent variables are measuring the constructs in the same metrics with equivalent reliabilities across all subgroups. Systematic procedures are outlined for testing these assumptions. PMID- 26810742 TI - A Significance Test For Congruence Coefficients For Cattell's Factors Matched By Scanning. AB - The personality theory of Cattell depends heavily on the methodology og factor analysis. One of the critical matters for the theory is the replication of factors both within and between variable domains, which depends on the development of significance levels for matching indices like the congruence coefficient. The tables of Schneewind & Cattell have been used to evaluate congruence coefficients, even though the tables are appropriately constructed and the null hypothesis which is tested is not appropriate. A Monte Carlo method is used to construct new tables that test the hypothesis that an independent set of random vectors has been matched. Less than half of the congruence coefficients reported by Cattell in two articles exceed the critical values thus created. There is some non-random structure in Cattell's results, but not enough to support the conclusion that factors have been replicated. PMID- 26810743 TI - Matched Determiners Vs. Factor Invariance: A Reply To Korth. AB - Korth (1978) does well to describe factor matching as vital to personality research but seriously underestimates the extent of successful matching both within and between cultures. His evaluation of matching of a set of factors is an advance, but the achievement of "diagonalization" of r[SUBc] coefficients in a matching matrix probably has a higher significance than his method would indicate. Regarding Monte Carlo determinations of r[SUBc] distributions, the writer maintains that treating loadings as random normal deviates is incorrect and that a special distribution (here presented) is required. Further, it is argued that "factor invariance," as commonly defined, is not the required proof of identify of determiners. Instead, the principles of real base factor analysis need to be applied to demonstrate degree of matching of determiners. A numerical illustration shows that when congruence is actually perfect for the real base factor patterns, it is not so for ordinary factor analysis patterns. Even in this framework the congruence, coefficient has weaknesses, and it is suggested that decisions be based on the joint outcome of r[SUBc] and 8, the salient variable similarity index. PMID- 26810744 TI - Definition And Measurement Of Three Processes Of Imagery Representation: Exploratory Studies Of Verbally Stimulated Imagery. AB - Three sets of experiments lend support to the hypothesis that there are at least three processes of imagery: (1) figural, in which a quasi-visual or other sensory representation of an object is made; (2) symbolic in which an abstract concepts is illustrated or symbolized by some imaginal representation; and (3) mimetic, in which a human experience is given a complex imaginal representation involving both envisionment and enactment or miming. Two types of scales for measuring stylistic differences in these three, processes are presented in detail. One type of scale is drawn from subjects' ratings of the ease and speed with which images are aroused by concrete, abstract, or personal words respectively. The other type of scale is drawn from subjects' ratings of the vividness of images aroused by various phrases specifically written to tap one or other of the hypothesized imagery processes. Two experiments are described in which the three processes are differentially activated by instructions as well as by type of stimulus material. In both experiments the expected interaction effects (between instructions and type of material) are found with p <.001. PMID- 26810745 TI - Superfactors P, E And N In A Comprehensive Factor Space. AB - Browne and Howarth, in a recent study, selected 400 items from 1726 non-repeated items appearing in previous personality studies, representing twenty hypothetical factors, analysis, followed by rotation, resulted in a multiplicity of factors, many of them similar to those hypothesized. A table is given of the intercorrelations between factors, but no higher order factor analysis was carried out. The writer's system predicts that three such factors should be found in any comprehensive study of this kind, and this paper reports a factor analysis of the correlations among the Browne and Howarth factors. A very clear three factor picture emerges, with the hypothetical psychcoticism, extraversion and neuroticism factors having very much the predicted loading pattern. It is concluded that primary factor analysis without extraction of higher order factors leaves the analysis incomplete and omits what may be the most important part of the whole procedur. The results are interpreted as supporting the writer's theoretical position. PMID- 26810746 TI - Behavior, Situation, And Rater Variance In Descriptions Of Leader Behaviors. AB - Confirmatory factor analysis was used to assess the degree to which behavior, situation, and rater factors explain variance in perceptions of leader behavior. Neither situational factors nor situational-behavior interactions explained much variance (less than 10 percent) in the observed variables; rater factors and behavior factors accounted for most of the explained variance. Peers appear to discriminate among fellow supervisors on the Initiating Structure dimension while subordinates are more likely to employ the Consideration dimension. It is felt that the data analysis descried in the present paper provides useful information not available through other data analytic methods and that other modes of data collection, such as interviews and observational checklists, may be desirable. PMID- 26810747 TI - An Empirical Comparison Of Two Minimum Residual Factor Extraction Methods. AB - Comrey and Harman & Jones have proposed different methods of factor analyzing a correlation matrix using on!y the off-diagonal elements. The purpose of such procedures is to avoid using the diagonal communality elements of the matrix theft are generally unknown and must be estimated. This study was undertaken to provide an empirical comparison of the two methods. The Comrey method was considerably faster but the Harman & Jones method produced higher derived communalities. Both methods gave very similar empirical rotated solutions. Implications of the results are discussed. This study was carried out in response to a question (personal communication) posed by Professor Jura Nunnally about the nature of the Comrey and Harman-Jones solutions. The authors wish to express their thanks to Harry Harman for providing a copy of his minres computer program. PMID- 26810748 TI - Comments On The Analysis Of Covariance With Repeated Measures Designs. AB - A comparison is made between analysis of covariance solutions obtained under the univariate and multivariate models in the case where an experimental design contains between- and within-subject factors, one dependent variable, and one observation per subject on the covariate. Modifications of analysis of variance procedures are described which yield exact ANCOVA solutions from ANOVAs performed on residual scores. PMID- 26810749 TI - Erratum for Eshghi et al., Leptospira interrogans lpxD Homologue Is Required for Thermal Acclimatization and Virulence. PMID- 26810750 TI - Correction for Dietrich et al., Differential Influence of Nutrient-Starved Mycobacterium tuberculosis on Adaptive Immunity Results in Progressive Tuberculosis Disease and Pathology. PMID- 26810751 TI - Correction for Echeverria et al., Endotoxin-Induced Endothelial Fibrosis Is Dependent on Expression of Transforming Growth Factors beta1 and beta2. PMID- 26810753 TI - Association between central and peripheral blood pressure and periodontal disease in patients with a history of myocardial infarction. AB - INTRODUCTION: Central and peripheral blood pressure (BP) and periodontal disease (PD) are considered to be related to the risk of cardiovascular disease. However, there is scarce evidence on the association between chronic PD and BP. OBJECTIVES: The aim of the study was to assess the relation between chronic PD, antibodies against Porphyromonas gingivalis (P.g.) gingipains and central and peripheral BP in high-risk patients with previous myocardial infarction. PATIENTS AND METHODS: We examined 99 patients (71 men and 28 women) 6 to 18 months after myocardial infarction. The periodontal status was assessed using the Community Periodontal Index (CPI). BP was measured noninvasively using the Mobil-O-Graph device. Antibody titers against P.g. gingipains were determined by an enzyme linked immunosorbent assay. The association between CPI and BP was assessed using logistic regression models. RESULTS: The mean age of participants was 60.5 +/-8.7 years. After the adjustment for age, sex, smoking, diabetes, number of antihypertensive drugs, hypercholesterolemia, body mass index, and left ventricular ejection fraction, an association was found between central and peripheral BP and the CPI. Patients from the CPI 3 + 4 group were found to have almost 3 times higher odds of central BP of 130/90 mmHg or higher and more than 3 times higher odds of peripheral BP of 140/90 mmHg or higher compared with patients from the CPI 1 + 2 group. CONCLUSIONS: The severity of PD was associated with increased central and peripheral BP. The association between BP and PD may partially explain the cardiovascular risk related to chronic PD. Proteolytic activity of P.g. gingipains was not associated with BP. PMID- 26810755 TI - What is changing in radiotherapy for the treatment of locally advanced nonsmall cell lung cancer patients? A review. AB - Radiotherapy treatment continues to have a relevant impact in the treatment of nonsmall cell cancer (NSCLC). Use of concurrent chemotherapy and radiotherapy is considered the gold standard in the treatment of locally advanced NSCLC but clinical outcomes are not satisfactory. Introduction of new radiotherapy technology and chemotherapy regimens are under investigation in this setting with the goal to improve unsatisfactory results. We report how radiotherapy is changing in the treatment of locally advanced NSCLC. PMID- 26810754 TI - Epigenetic silencing of CREB3L1 by DNA methylation is associated with high-grade metastatic breast cancers with poor prognosis and is prevalent in triple negative breast cancers. AB - BACKGROUND: CREB3L1 (cAMP-responsive element-binding protein 3-like protein 1), a member of the unfolded protein response, has recently been identified as a metastasis suppressor in both breast and bladder cancer. METHODS: Quantitative real time PCR (qPCR) and immunoblotting were used to determine the impact of histone deacetylation and DNA methylation inhibitors on CREB3L1 expression in breast cancer cell lines. Breast cancer cell lines and tumor samples were analyzed similarly, and CREB3L1 gene methylation was determined using sodium bisulfite conversion and DNA sequencing. Immunohistochemistry was used to determine nuclear versus cytoplasmic CREB3L1 protein. Large breast cancer database analyses were carried out to examine relationships between CREB3L1 gene methylation and mRNA expression in addition to CREB3L1 mRNA expression and prognosis. RESULTS: This study demonstrates that the low CREB3L1 expression previously seen in highly metastatic breast cancer cell lines is caused in part by epigenetic silencing. Treatment of several highly metastatic breast cancer cell lines that had low CREB3L1 expression with DNA methyltransferase and histone deacetylase inhibitors induced expression of CREB3L1, both mRNA and protein. In human breast tumors, CREB3L1 mRNA expression was upregulated in low and medium grade tumors, most frequently of the luminal and HER2 amplified subtypes. In contrast, CREB3L1 expression was repressed in high-grade tumors, and its loss was most frequently associated with triple negative breast cancers (TNBCs). Importantly, bioinformatics analyses of tumor databases support these findings, with methylation of the CREB3L1 gene associated with TNBCs, and strongly negatively correlated with CREB3L1 mRNA expression. Decreased CREB3L1 mRNA expression was associated with increased tumor grade and reduced progression-free survival. An immunohistochemistry analysis revealed that low-grade breast tumors frequently had nuclear CREB3L1 protein, in contrast to the high-grade breast tumors in which CREB3L1 was cytoplasmic, suggesting that differential localization may also regulate CREB3L1 effectiveness in metastasis suppression. CONCLUSIONS: Our data further strengthens the role for CREB3L1 as a metastasis suppressor in breast cancer and demonstrates that epigenetic silencing is a major regulator of the loss of CREB3L1 expression. We also highlight that CREB3L1 expression is frequently altered in many cancer types suggesting that it could have a broader role in cancer progression and metastasis. PMID- 26810756 TI - Isoflurane postconditioning induces concentration- and timing-dependent neuroprotection partly mediated by the GluR2 AMPA receptor in neonatal rats after brain hypoxia-ischemia. AB - BACKGROUND: It has been demonstrated that preconditioning with 1.5 % isoflurane reduces hypoxia/ischemia (HI)-induced brain loss/injury in neonatal rats. Ca(2+) influx mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) is involved in HI-induced neuronal death. Here, we investigated the effective concentrations and time windows for neuroprotection by isoflurane postconditioning in neonatal rats after brain HI and determined whether GluR2-containing AMPARs mediate this neuroprotection. METHODS: Seven-day old Sprague-Dawley (SD) rats were randomly divided into eight groups (n = 40 in each). The rats underwent left common carotid arterial ligation (brain HI) or sham surgery, followed by exposure to 8 % oxygen for 2 h at 37 degrees C in a thermoregulated environment. Post-conditioning with 1, 1.5, or 2 % isoflurane for 30 min was performed immediately after brain HI. Others were post-treated with 1.5 % isoflurane for 30 min at 3, 6, and 12 h after brain HI. The weight ratio, neuronal density ratio in the ventral posteromedial thalamic nucleus, and retrosplenial granular cortex of left to right cerebral hemispheres at 7 days after brain HI were evaluated in all groups. Cerebral hemispheres were harvested for Western-blot analysis of GluR2 on the cellular membranes 24 h after HI or sham surgery in neonatal rats from the sham group, the HI group, and the HI + immediate exposure to the 1.5 % isoflurane group. In another experiment, the function of learning and memory were assessed in adolescence (4 weeks) using Morris water maze. RESULTS: Compared with the control (sham) group, brain HI decreased the weight ratio and the neuronal density ratio in the ventral posteromedial thalamic nucleus and the retrosplenial granular cortex of the left to right cerebral hemispheres (p < 0.05). These effects of brain HI were reduced by postconditioning with 1.5 or 2 % isoflurane for 30 min within 6 h of HI, which coincided with the results of Morris water maze. GluR2 protein expression on cellular membranes was reduced after HI compared with sham surgery group (p < 0.05); this down-regulation was attenuated by isoflurane postconditioning. CONCLUSIONS: Postconditioning with 1.5 and 2 % isoflurane affords neuroprotection in neonatal rats. The time window for isoflurane postconditioning to be effective against neonatal HI-induced brain injury was 0-6 h after HI. This protection may be mediated by GluR2-containing AMPARs. PMID- 26810757 TI - Engraftment of enteric neural progenitor cells into the injured adult brain. AB - BACKGROUND: A major area of unmet need is the development of strategies to restore neuronal network systems and to recover brain function in patients with neurological disease. The use of cell-based therapies remains an attractive approach, but its application has been challenging due to the lack of suitable cell sources, ethical concerns, and immune-mediated tissue rejection. We propose an innovative approach that utilizes gut-derived neural tissue for cell-based therapies following focal or diffuse central nervous system injury. RESULTS: Enteric neuronal stem and progenitor cells, able to differentiate into neuronal and glial lineages, were isolated from the postnatal enteric nervous system and propagated in vitro. Gut-derived neural progenitors, genetically engineered to express fluorescent proteins, were transplanted into the injured brain of adult mice. Using different models of brain injury in combination with either local or systemic cell delivery, we show that transplanted enteric neuronal progenitor cells survive, proliferate, and differentiate into neuronal and glial lineages in vivo. Moreover, transplanted cells migrate extensively along neuronal pathways and appear to modulate the local microenvironment to stimulate endogenous neurogenesis. CONCLUSIONS: Our findings suggest that enteric nervous system derived cells represent a potential source for tissue regeneration in the central nervous system. Further studies are needed to validate these findings and to explore whether autologous gut-derived cell transplantation into the injured brain can result in functional neurologic recovery. PMID- 26810759 TI - What Is the Prognostic Value of Intermediate Lactate Level Elevations in Emergency Department Patients With Suspected Infection? PMID- 26810758 TI - Noninvasive End Tidal CO2 Is Unhelpful in the Prediction of Complications in Deliberate Drug Poisoning. AB - STUDY OBJECTIVE: We study the performance of capnometry in the detection of early complications after deliberate drug poisoning. METHODS: This was a prospective cohort study of self-poisoned adult patients who presented at an emergency department (ED) between April 20, 2012, and May 6, 2014. Patients who ingested at least 1 neurologic or respiratory depressant drug were included. The primary outcome was the predictive value of an end tidal CO2 (etco2) measurement greater than or equal to 50 mm Hg for the detection of early complications defined a priori by hypoxia requiring oxygen greater than or equal to 3 L/min, bradypnea less than or equal to 10 breaths/min, or ICU admission after intubation or antidote administration because of unresponsiveness to pain or respiratory arrest. Consciousness scales and clinical data were recorded at admission and every 30 minutes. Noninvasive etco2 was continuously measured for 2 hours after inclusion unless the patient was admitted to the ICU. Patients and physicians were blinded to etco2 values. RESULTS: Two hundred one patients were included, 35 of whom exhibited at least 1 complication. An etco2 measurement greater than or equal to 50 mm Hg predicted the onset of a complication, with a sensitivity of 46% (95% confidence interval [CI] 29% to 63%) and a specificity of 80% (95% CI 73% to 86%), leading to a positive predictive value of 33% (95% CI 20% to 48%) and a negative predictive value of 88% (95% CI 81% to 92%). etco2 was less able to predict complications than the Glasgow Coma Scale score at inclusion. CONCLUSION: Capnometry in isolation does not provide adequate prediction of early complications in self-poisoned patients referred to the ED. A dynamic minute-by minute assessment of etco2 could be more predictive. PMID- 26810760 TI - Fruit and vegetable consumption and all-cause mortality: evidence from a large Australian cohort study. AB - BACKGROUND: There is growing evidence for a relationship between fruit and vegetable consumption and all-cause mortality. Few studies, however, specifically explored consuming raw versus cooked vegetables in relation to health and mortality outcomes. The purpose of this study was to examine the relation of all cause mortality with: a) fruit and vegetable consumption, either combined or separately; b) the consumption of raw versus cooked vegetables in a large cohort of Australian middle-aged and older adults. METHODS: The sample included 150,969 adults aged 45 years and over from the 45 and Up Study, a prospective cohort study conducted in New South Wales, Australia. Self-reported baseline questionnaire data (2006-09) were linked to mortality data up to June 2014. Fruit and vegetable consumption was assessed by validated short questions. Crude and adjusted hazard ratios were calculated using Cox proportional hazard models. Covariates included socio-demographic characteristics, health-related and dietary variables. RESULTS: During a mean follow-up of 6.2 years, 6038 (4 %) participants died from all causes. In the fully adjusted models, increasing consumption of fruit and vegetables combined was associated with reductions in all-cause mortality, with the highest risk reduction seen up to 7 serves/day or more of fruit and vegetables (P for trend = 0.002, hazard ratio for highest versus lowest consumption quartile: 0.90; 95 % confidence interval: 0.84, 0.97). Separate consumption of fruit and vegetables, as well as consumption of raw or cooked vegetables, were associated with a reduced risk of all-cause mortality in the crude and minimally adjusted models (all P for trend <0.05). With the exception of raw vegetables, these associations remained significant in the fully adjusted models (all P for trend <0.05). Age and sex were significant effect modifiers of the association between fruit and vegetable consumption and all-cause mortality. CONCLUSIONS: Fruit and vegetable consumption were inversely related to all-cause mortality in this large Australian cohort. Further studies examining the effects of raw versus cooked vegetables are needed. PMID- 26810761 TI - Forty-eight novel mutations causing biotinidase deficiency. AB - Biotinidase deficiency is an autosomal recessively inherited disorder that results in the inability to recycle the vitamin biotin and is characterized by neurological and cutaneous symptoms. The symptoms can be ameliorated or prevented by administering pharmacological doses of biotin. Since 2008, approximately 300 samples have been submitted to ARUP's Molecular Sequencing Laboratory for biotinidase mutation analysis. Of these, 48 novel alterations in the biotinidase gene have been identified. Correlating the individual's serum enzymatic activity with the genotype, we have been able to determine the effect of the novel alteration on enzyme activity and, thereby, determine its likelihood of being pathogenic in 44 of these individuals. The novel mutations and uncertain alterations have been added to the database established by ARUP (http://arup.utah.edu/database/BTD/BTD_welcome.phps) to help clinicians make decisions about management and to better counsel their patients based on their genotypes. PMID- 26810762 TI - Idiopathic pleuroparenchymal fibroelastosis, a new idiopathic interstitial pneumonia: A case report. AB - Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare disease, idiopathic in most of the cases described in the literature. We report the case of a 55-year old patient, non-smoker with tuberculosis treated in his youth, starting with progressive dyspnoea and cough, with radiographic abnormalities consisting of pleural thickening, bronchiectasis and structural distortion predominantly in the upper lobes. Due to functional impairment and persistent radiographic abnormalities, biopsy by video-assisted thoracoscopic surgical was decided. The presence of striking elastosis, absence of interstitial damage and abrupt boundary of the fibrous lesion with healthy lung allowed the diagnosis of IPPFE. Currently, the patient has no specific treatment and is in follow-up in the Transplant Unit. PMID- 26810764 TI - Dietary intake and food contributors of polyphenols in adults and elderly adults of Sao Paulo: a population-based study. AB - A comprehensive estimation of polyphenol intake is needed to gain a better understanding of the association between polyphenol-rich food intake and the potential effects of this intake on chronic diseases. The aim of this study was to estimate the intake of polyphenols and the major dietary contributors in the population of Sao Paulo. Data were obtained from the Health Survey-Sao Paulo (ISA Capital 2008) and were reported for 1103 adults and elderly adults. Food intake was estimated by one 24-h dietary recall (24HR). Polyphenol intake was calculated by matching food consumption data from the 24HR with the polyphenol content in foods listed in the Phenol-Explorer database. The mean total intake of polyphenols was 377.5 (se 15.3) mg/d. The main polyphenol classes were phenolic acids (284.8 (se 15.9) mg/d) and flavonoids (54.6 (se 3.5) mg/d). Intakes were higher in the elderly adults than in other adults (P<0.001) and higher in individuals with lower educational level (P=0.01) and current smokers (P=0.02). The main dietary contributors for total polyphenols were coffee (70.5 %), citrus fruits (4.6 %) and tropical fruits (3.4 %). Coffee was the major source of polyphenols, providing 266.2 (se 16.5) mg/d, and contributed 92.3 % of the phenolic acids and 93.1 % of the alkylmethoxyphenols. These findings will be useful for assessing the potential role on health of polyphenols and specific polyphenol-rich foods, such as coffee, and enable a comparison with people from other countries. PMID- 26810763 TI - Signaling mechanisms of plant cryptochromes in Arabidopsis thaliana. AB - Cryptochromes (CRY) are flavoproteins that direct a diverse array of developmental processes in response to blue light in plants. Conformational changes in CRY are induced by the absorption of photons and result in the propagation of light signals to downstream components. In Arabidopsis, CRY1 and CRY2 serve both distinct and partially overlapping functions in regulating photomorphogenic responses and photoperiodic flowering. For example, both CRY1 and CRY2 regulate the abundance of transcription factors by directly reversing the activity of E3 ubiquitin ligase on CONSTITUTIVE PHOTOMORPHOGENIC 1 and SUPPRESSOR OF PHYA-105 1 complexes in a blue light-dependent manner. CRY2 also specifically governs a photoperiodic flowering mechanism by directly interacting with a transcription factor called CRYPTOCHROME-INTERACTING BASIC-HELIX-LOOP HELIX. Recently, structure/function analysis of CRY1 revealed that the CONSTITUTIVE PHOTOMORPHOGENIC 1 independent pathway is also involved in CRY1 mediated inhibition of hypocotyl elongation. CRY1 and CRY2 thus not only share a common pathway but also relay light signals through distinct pathways, which may lead to altered developmental programs in plants. PMID- 26810765 TI - Why don't adolescents finish the HPV vaccine series? A qualitative study of parents and providers. AB - OBJECTIVE: To describe why adolescent females who initiated HPV vaccination completed or did not complete the series. METHODS: Semi-structured interviews were conducted with parents/guardians of 11-17 year old female adolescents and their pediatric primary care providers in one inner-city public clinic and three private practices to ascertain why girls who initiated HPV vaccination did or did not complete the series. Qualitative analysis was used to identify perceived barriers and facilitators of completion. RESULTS: 65 parents/guardians participated: 37 whose daughters received 1 or 2 HPV vaccine doses and 28 whose daughters completed the series. 89% (n = 33) of parents who did not complete the series intended to do so, but were not reminded by the clinic or encountered logistical barriers. Four (11%) decided to stop the vaccine series. 33 providers participated: 24 physicians, 3 nurse practitioners, and 6 registered nurses. Half (n = 14, 52%) of the providers said they told parents when the next doses were due but relied on parents to schedule appointments, 11 (41%) scheduled the second dose when the first dose was given, and 2 (7%) tried to immunize patients when they returned for other appointments. None of the four practices had a reminder/recall system in place to ensure series completion. Of note, neither parents nor providers stated that the need for three doses was a barrier to series completion. CONCLUSIONS: Most failure to complete the HPV vaccine series occurred because providers expected parents to make appointments while parents expected to be reminded. Increased use of reminder/recall systems and team-based care with clear communication of expectations regarding appointment scheduling could increase completion rates. PMID- 26810769 TI - Good Response to Doxycycline in Hailey-Hailey Disease. PMID- 26810768 TI - Disclosing Pleiotropic Effects During Genetic Risk Assessment for Alzheimer Disease: A Randomized Trial. AB - BACKGROUND: Increasing use of genetic testing raises questions about disclosing secondary findings, including pleiotropic information. OBJECTIVE: To determine the safety and behavioral effect of disclosing modest associations between apolipoprotein E (APOE) genotype and coronary artery disease (CAD) risk during APOE-based genetic risk assessments for Alzheimer disease (AD). DESIGN: Randomized, multicenter equivalence clinical trial. (ClinicalTrials.gov: NCT00462917). SETTING: 4 teaching hospitals. PARTICIPANTS: 257 asymptomatic adults were enrolled, 69% of whom had 1 AD-affected first-degree relative. INTERVENTION: Disclosure of genetic risk information about AD and CAD (AD+CAD) or AD only (AD-only). MEASUREMENTS: Primary outcomes were Beck Anxiety Inventory (BAI) and Center for Epidemiologic Studies Depression Scale (CES-D) scores at 12 months. Secondary outcomes were all measures at 6 weeks and 6 months and test related distress and health behavior changes at 12 months. RESULTS: At 12 months, mean BAI scores were 3.5 in both the AD-only and AD+CAD groups (difference, 0.0 [95% CI, -1.0 to 1.0]), and mean CES-D scores were 6.4 and 7.1 in the AD-only and AD+CAD groups, respectively (difference, 0.7 [CI, -1.0 to 2.4]). Both confidence bounds fell within the equivalence margin of +/-5 points. Among carriers of the APOE epsilon4 allele, distress was lower in the AD+CAD groups (difference, -4.8 [CI, -8.6 to -1.0]) (P = 0.031 for the interaction between group and APOE genotype). Participants in the AD+CAD groups also reported more health behavior changes, regardless of APOE genotype. LIMITATIONS: Outcomes were self-reported by volunteers without severe anxiety, severe depression, or cognitive problems. Analyses omitted 33 randomly assigned participants. CONCLUSION: Disclosure of pleiotropic information did not increase anxiety or depression and may have decreased distress among persons at increased risk for 2 conditions. Providing risk modification information about CAD improved health behaviors. Findings highlight the potential benefits of disclosure of secondary genetic findings when options exist for decreasing risk. PRIMARY FUNDING SOURCE: National Human Genome Research Institute. PMID- 26810770 TI - Depression, patient characteristics, and attachment style: correlates and mediators of medication treatment adherence in a racially diverse primary care sample. AB - BACKGROUND: The depth and breadth of problems related to depressive symptomatology and optimal treatment outcomes, including medication treatment adherence, have long been documented in the literature. Missing are clear explanations as to what factors and patient characteristics may account for lack of medication treatment adherence. OBJECTIVES: The two objectives of the current study were to examine the predictive strength of depression, patient characteristics, and patient attachment style regarding medication treatment adherence and to consider the extent to which attachment styles mediate the relation between depression and medication treatment adherence. METHOD: Participants in the present study were 237 racially diverse American primary care patients with a diagnosis of hypertension who were participants in a clinical trial. Depression, patient characteristics, attachment style, and medication treatment adherence were assessed. RESULTS: Partly consistent with our four hypotheses, the following results were found: (a) Black American, younger, never married, and poorer patients had lower medication treatment adherence (b) depression was significantly associated with lower self-reported medication adherence; (c) insecure-dismissing attachment style was related to lower medication adherence; and (d) insecure-dismissing attachment style mediates the relation between depression and medication treatment adherence by exacerbating the negative association. CONCLUSION: Physicians and other primary care providers should consider how depressive symptomatology, patient characteristics, and attachment style may inform the treatment plans they put forward and the extent to which patients may adhere to those treatment plans. PMID- 26810771 TI - Gene methylation profile of gastric cancerous tissue according to tumor site in the stomach. AB - BACKGROUND: There is considerable information on the methylation of the promoter regions of different genes involved in gastric carcinogenesis. However, there is a lack of information on how this epigenetic process differs in tumors originating at different sites in the stomach. The aim of this study is to assess the methylation profiles of the MLH1, MGMT, and DAPK-1 genes in cancerous tissues from different stomach sites. METHODS: Samples were acquired from 81 patients suffering stomach adenocarcinoma who underwent surgery for gastric cancer in the Lithuanian University of Health Sciences Hospital Kaunas Clinics in 2009-2012. Gene methylation was investigated with methylation-specific PCR. The study was approved by the Lithuanian Biomedical Research Ethics Committee. RESULTS: The frequencies of methylation in cancerous tissues from the upper, middle, and lower thirds of the stomach were 11.1, 23.1, and 45.4%, respectively, for MLH1; 22.2, 30.8, and 57.6%, respectively, for MGMT; and 44.4, 48.7, and 51.5%, respectively, for DAPK-1. MLH1 and MGMT methylation was observed more often in the lower third of the stomach than in the upper third (p < 0.05). In the middle third, DAPK-1 promoter methylation was related to more-advanced disease in the lymph nodes (N2 3 compared with N0-1 [p = 0.02]) and advanced tumor stage (stage III rather than stages I-II [p = 0.05]). MLH1 and MGMT methylation correlated inversely when the tumor was located in the lower third of the stomach (coefficient, -0.48; p = 0.01). DAPK-1 and MLH1 methylation correlated inversely in tumors in the middle third of the stomach (coefficient, -0.41; p = 0.01). CONCLUSION: Gene promoter methylation depends on the gastric tumor location. PMID- 26810772 TI - Ethical and Societal Questions Loom Large as Gene Editing Moves Closer to the Clinic. PMID- 26810774 TI - Hoyeraal-Hreidarsson Syndrome due to PARN Mutations: Fourteen Years of Follow-Up. AB - BACKGROUND: Hoyeraal-Hreidarsson syndrome is a dyskeratosis congenita-related telomere biology disorder that presents in infancy with intrauterine growth retardation, immunodeficiency, and cerebellar hypoplasia in addition to the triad of nail dysplasia, skin pigmentation, and oral leukoplakia. Individuals with Hoyeraal-Hreidarsson syndrome often develop bone marrow failure in early childhood. Germline mutations in DKC1, TERT, TINF2, RTEL1, ACD, or PARN cause about 60% of individuals with Hoyeraal-Hreidarsson syndrome. PATIENT DESCRIPTION: We describe 14 years of follow-up of an individual with Hoyeraal-Hreidarsson syndrome who initially presented as an infant with intrauterine growth retardation, microcephaly, and central nervous system calcifications. He was diagnosed with Hoyeraal-Hreidarsson syndrome at age 6 years and had a complicated medical history including severe developmental delay, cerebellar hypoplasia, esophageal and urethral stenosis, hip avascular necrosis, immunodeficiency, and bone marrow failure evolving to myelodysplastic syndrome requiring hematopoietic cell transplantation at age 14 years. He had progressive skin pigmentation, oral leukoplakia, and nail dysplasia leading to anonychia. Whole exome sequencing identified novel biallelic variants in PARN. CONCLUSIONS: This patient illustrates that the constellation of intrauterine growth retardation, central nervous system calcifications, and cerebellar hypoplasia, esophageal or urethral stenosis, and cytopenias, in the absence of congenital infection, may be due to Hoyeraal-Hreidarsson syndrome. Early diagnosis of Hoyeraal-Hreidarsson syndrome is important to optimize medical management and provide genetic counseling. PMID- 26810775 TI - What Factors Contribute to Headache-Related Disability in Teens? AB - BACKGROUND: Our aim was to describe the relationship between risk factors, such as stress, depression, and anxiety, and potentially protective factors against pediatric headache-related disability, such as mindfulness, resilience, and self compassion, and to determine teens' interest in mind-body skills training to help reduce headache-related disability. METHODS: This was a cross-sectional survey among adolescents seen in an academic neurology clinic reporting four or more headaches monthly using standardized instruments to determine the relationship between putative risk and protective factors as well as physiologic markers of inflammation and vagal tone and headache-related disability. RESULTS: Among the 29 participants, 31% were male, the average age was 14.8 years, average headache frequency was 11.6 per month, and the most commonly reported trigger was stress (86%). The only risk or protective factor significantly associated with headache related disability was depression (r = 0.52, P = 0.004). Depression was negatively correlated with mindfulness, resilience, and self-compassion (P < 0.01 each) and positively correlated with stress, sleep disturbance, and anxiety (P < 0.01 each). Biomarkers of vagal tone and inflammation were correlated with each other but not with headache-related disability or depression. There was strong interest in learning skills like slow, deep breathing practices supported by a smart phone application to reduce stress and the negative impact of headaches on daily life. DISCUSSION: Among teens with frequent migraine headaches, depression is the strongest risk factor for headache-related disability. Stress is viewed as a headache trigger, and teens reported wanting to learn simple stress management strategies supported by a smart phone application to help reduce headache-related disability. PMID- 26810777 TI - Cross-sectional and longitudinal analyses of everyday memory lapses in older adults. AB - Everyday memory lapses experienced by older adults (OAs) were examined using a daily-diary checklist and retrospective questionnaire. In Experiment 1, 138 younger and 138 OAs indicated the frequency of forgetting of 16 memory lapses, and whether each occurred daily during the course of a week. OAs reported more memory lapses on the questionnaire, but not the daily diary. OAs reported more frequently forgetting names and words, while younger adults had more difficulty with appointments and personal dates. Fewer memory lapses on the daily diary were related to better performance on a laboratory-memory measure for OAs. In Experiment 2, 62 OAs returned for a five-year follow-up and endorsed experiencing more memory lapses on the daily diary compared to baseline, specifically forgetting more names and words, but not the retrospective questionnaire. Daily checklist memory lapses again correlated with the laboratory-memory measure. A daily checklist may be a viable way to assess everyday memory lapses. PMID- 26810780 TI - Arteriovenous malformation of the uterine cervix. AB - A uterine arteriovenous malformation (AVM) is an uncommon cause of uterine bleeding. Location of this lesion in the uterine cervix is exceptional. We report a case of a 34-year-old woman who presented with chronic menorrhagias and hypochromic anemia. A sonographic study revealed a 10-cm, fundal, intramural, uterine well-circumscribed mass that distorted the endometrial cavity. The patient underwent hysterectomy for a large uterine leiomyoma. The pathological study revealed an incidental AVM of the posterior half of the cervix measuring 5.5 cm in major diameter. We suggest that in our case cervical AVM might have occurred due to a large corporal leiomyoma distorting the uterine circulation. Differential diagnosis includes capillary hemangioma, venous malformation, or arteriovenous fistula. PMID- 26810781 TI - Pharmacologically effective red yeast rice preparations marketed as dietary supplements illustrated by a case report. AB - This paper reports a typical statin-related adverse reaction from a red yeast rice (RYR) supplement and the analytical findings from the supplement. It also examines the regulatory framework governing botanical supplements in Europe. Two key events that shaped the current regulatory framework are reviewed. First, the Hecht-Pharma judgement by the European Court of Justice (ECJ) that inverted the precautionary principle in the Medicines Act to a reactionary principle. Following the Hecht-Pharma judgement, pharmacological active dietary supplements can be sold until sufficient signals of harm show that they are an unregistered medicine, placing a huge burden on regulatory authorities. Secondly, the European Food Safety Authority (EFSA) in 2011 approved the first health claim for pharmacologically active RYR dietary supplements. If the current regulatory status for pharmacologically active RYR dietary supplements does not permit adequate warning and active monitoring of adverse drug reactions, then the current regulatory framework may not be adequate to ensure consumer safety.Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26810782 TI - Analysis of Glial Distribution in Drosophila Adult Brains. AB - Neurons and glia are the two major cell types in the nervous system and work closely with each other to program neuronal interplay. Traditionally, neurons are thought to be the major cells that actively regulate processes like synapse formation, plasticity, and behavioral output. Glia, on the other hand, serve a more supporting role. To date, accumulating evidence has suggested that glia are active participants in virtually every aspect of neuronal function. Despite this, fundamental features of how glia interact with neurons, and their spatial relationships, remain elusive. Here, we describe the glial cell population in Drosophila adult brains. Glial cells extend and tightly associate their processes with major structures such as the mushroom body (MB), ellipsoid body (EB), and antennal lobe (AL) in the brain. Glial cells are distributed in a more concentrated manner in the MB. Furthermore, subsets of glia exhibit distinctive association patterns around different neuronal structures. Whereas processes extended by astrocyte-like glia and ensheathing glia wrap around the MB and infiltrate into the EB and AL, cortex glia stay where cell bodies of neurons are and remain outside of the synaptic regions structured by EB or AL. PMID- 26810784 TI - Electroacupuncture protects against articular cartilage erosion by inhibiting mitogen-activated protein kinases in a rat model of osteoarthritis. AB - OBJECTIVE: The therapeutic effects of electroacupuncture (EA) on osteoarthritis (OA) are well documented; however, the precise mechanisms of action have not yet been fully elucidated. The present study aimed to investigate the effect of EA on cartilage in an experimental animal model of OA induced by anterior cruciate ligament transection (ACLT) and to examine for concomitant changes in the expression of mitogen-activated protein kinases (MAPKs) in the articular cartilage. METHODS: Thirty-three-month-old male Sprague Dawley rats were randomly divided into the following three groups (n=10 each): sham operated group (Control group), ACLT without treatment (ACLT group), and ACLT with EA treatment (ACLT+EA group). One week after ACLT, rats in the ACLT+EA group received 12 weeks of EA treatment. Histological analysis and quantitative real-time PCR were used to investigate the effects of EA on cartilage morphology (quantified using modified Mankin scores) and expression of MAPKs (p38, c-Jun N-terminal kinase (c-Jun), and extracellular signal-regulated kinase (ERK)1), respectively. RESULTS: ACLT produced coarse cartilage surfaces, fibrous degeneration, and fissuring, all of which were suppressed by EA treatment. Although Mankin scores in the ACLT+EA group were significantly higher compared to the Control group (p<0.01), they were significantly lower than the (untreated) ACLT group (p<0.01). The increase in mRNA expression of p38, c-Jun, ERK1, and matrix metalloproteinase (MMP)-13 observed in cartilage after ACLT was significantly inhibited by EA. CONCLUSIONS: EA appears to prevent the degeneration of articular cartilage, at least partly through regulation of MMP-13 and inhibition of MAPKs in the cartilage of rats with ACLT-induced OA. PMID- 26810785 TI - Global Prevalence of Past-year Violence Against Children: A Systematic Review and Minimum Estimates. AB - CONTEXT: Evidence confirms associations between childhood violence and major causes of mortality in adulthood. A synthesis of data on past-year prevalence of violence against children will help advance the United Nations' call to end all violence against children. OBJECTIVES: Investigators systematically reviewed population-based surveys on the prevalence of past-year violence against children and synthesized the best available evidence to generate minimum regional and global estimates. DATA SOURCES: We searched Medline, PubMed, Global Health, NBASE, CINAHL, and the World Wide Web for reports of representative surveys estimating prevalences of violence against children. STUDY SELECTION: Two investigators independently assessed surveys against inclusion criteria and rated those included on indicators of quality. DATA EXTRACTION: Investigators extracted data on past-year prevalences of violent victimization by country, age group, and type (physical, sexual, emotional, or multiple types). We used a triangulation approach which synthesized data to generate minimum regional prevalences, derived from population-weighted averages of the country-specific prevalences. RESULTS: Thirty-eight reports provided quality data for 96 countries on past-year prevalences of violence against children. Base case estimates showed a minimum of 50% or more of children in Asia, Africa, and Northern America experienced past year violence, and that globally over half of all children-1 billion children, ages 2-17 years-experienced such violence. LIMITATIONS: Due to variations in timing and types of violence reported, triangulation could only be used to generate minimum prevalence estimates. CONCLUSIONS: Expanded population-based surveillance of violence against children is essential to target prevention and drive the urgent investment in action endorsed in the United Nations 2030 Sustainable Development Agenda. PMID- 26810783 TI - An Overview of Genome-Wide Association Studies in Alzheimer's Disease. AB - Genome-wide association studies (GWASs) have revealed a plethora of putative susceptibility genes for Alzheimer's disease (AD). With the sole exception of the APOE gene, these AD susceptibility genes have not been unequivocally validated in independent studies. No single novel functional risk genetic variant has been identified. In this review, we evaluate recent GWASs of AD, and discuss their significance, limitations, and challenges in the investigation of the genetic spectrum of AD. PMID- 26810786 TI - Chronic Fatigue Syndrome at Age 16 Years. AB - BACKGROUND: In the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, chronic disabling fatigue lasting >=6 months affected 1.3% of 13-year olds, was equally common in boys and girls, and became more prevalent with increasing family adversity. METHODS: ALSPAC data were used to estimate the prevalence of chronic fatigue syndrome (CFS) at age 16 years, defined by parental report of unexplained disabling fatigue lasting >=6 months. We investigated gender and a composite 14-item family adversity index as risk factors. School absence data were obtained from the National Pupil Database. Multiple imputation was used to address bias caused by missing data. RESULTS: The prevalence of CFS was 1.86% (95% confidence interval [CI]: 1.47 to 2.24). After excluding children with high levels of depressive symptoms, the prevalence was 0.60% (95% CI: 0.37 to 0.84). Authorized school absences were much higher (mean difference: 35.6 [95% CI: 26.4 to 44.9] half-day sessions per academic year) and reported depressive symptoms were much more likely (odds ratio [OR]: 11.0 [95% CI: 5.92 to 20.4]) in children with CFS than in those without CFS. Female gender (OR: 1.95 [95% CI: 1.33 to 2.86]) and family adversity (OR: 1.20 [95% CI: 1.01 to 1.42] per unit family adversity index) were also associated with CFS. CONCLUSIONS: CFS affected 1.9% of 16-year-olds in a UK birth cohort and was positively associated with higher family adversity. Gender was a risk factor at age 16 years but not at age 13 years or in 16-year-olds without high levels of depressive symptoms. PMID- 26810788 TI - Prevention and Management of Procedural Pain in the Neonate: An Update. AB - The prevention of pain in neonates should be the goal of all pediatricians and health care professionals who work with neonates, not only because it is ethical but also because repeated painful exposures have the potential for deleterious consequences. Neonates at greatest risk of neurodevelopmental impairment as a result of preterm birth (ie, the smallest and sickest) are also those most likely to be exposed to the greatest number of painful stimuli in the NICU. Although there are major gaps in knowledge regarding the most effective way to prevent and relieve pain in neonates, proven and safe therapies are currently underused for routine minor, yet painful procedures. Therefore, every health care facility caring for neonates should implement (1) a pain-prevention program that includes strategies for minimizing the number of painful procedures performed and (2) a pain assessment and management plan that includes routine assessment of pain, pharmacologic and nonpharmacologic therapies for the prevention of pain associated with routine minor procedures, and measures for minimizing pain associated with surgery and other major procedures. PMID- 26810789 TI - Poly(TEMPO)/Zinc Hybrid-Flow Battery: A Novel, "Green," High Voltage, and Safe Energy Storage System. AB - The combination of a polymer-based 2,2,6,6-tetramethylpiperidinyl-N-oxyl (TEMPO) catholyte and a zinc anode, together with a cost-efficient size-exclusion membrane, builds a new type of semi-organic, "green," hybrid-flow battery, which features a high potential range of up to 2 V, high efficiencies, and a long life time. PMID- 26810790 TI - Quinoline biodegradation by filamentous fungus Cunninghamella elegans and adaptive modifications of the fungal membrane composition. AB - Quinoline, which belongs to N-heterocyclic compounds, occurs naturally in the environment and is used in numerous industrial processes. The structures of various chemicals, such as dyes and medicines, are based on this compound. Due to that fact, quinoline and its derivatives are widely distributed in environment and can exert toxic effects on organisms from different trophic levels. The ability of the filamentous fungus Cunninghamella elegans IM 1785/21Gp to degrade quinoline and modulate the membrane composition in response to the pollutant was studied. C. elegans IM 1785/21Gp removes quinoline with high efficiency and transforms the pollutant into two novel hydroxylated derivatives, 2 hydroxyquinoline and 3-hydroxyquinoline. Moreover, due to the disruption in the membrane stability by quinoline, C. elegans IM 1785/21Gp modulates the fatty acid composition and phospholipid profile. PMID- 26810791 TI - Effects of perchlorate bioaccumulation on Spodoptera litura growth and sex ratio. AB - Perchlorate (ClO4 (-)) pollution is widespread in the natural environment, but the effects of ClO4 (-) on the terrestrial insects are rarely studied. Here, when phytophagous insect Spodoptera litura larvae were fed on the diets with different ClO4 (-) concentrations, changes in their life-history traits were recorded; ClO4 (-) accumulations in feces and insect body were detected. The results demonstrated that ClO4 (-) bioaccumulation in insect at the different developmental stages was ranked in the order: adults > pupae > the 4th > 5th > 6th instar larvae. Besides, ClO4 (-) accumulations in the feces were ranked in the order: the 6th > 5th > 4th instar larvae. The ClO4 (-) accumulations in female pupae and adults were significantly higher than that in males. ClO4 (-) bioaccumulation in insect prolonged larval development time and caused a skewed sex ratio (the percentage of males at metamorphosis significantly decreased) under 100 to 200 mg ClO4 (-)/kg treatment. Therefore, ClO4 (-) accumulations in S. litura body presented developmental stage-, sex-specific pattern, and the sex specific ClO4 (-) accumulations resulted in difference of sex ratio. These effects were observed at concentrations reported in natural environments contaminated with ClO4 (-), suggesting that this contaminant may pose a threat to the normal development and growth of this insect species. PMID- 26810795 TI - Fasting glycaemia to simplify screening for gestational diabetes. AB - OBJECTIVE: Recommendations in Switzerland on screening for gestational diabetes endorse the International Association of Diabetes in Pregnancy Study Group consensus. As universal testing is time consuming and glucose loading is unpleasant, the recommendations include a simplification, not performing the glucose loading in women with fasting glycaemia <4.4 mmol/l. Our objective was to evaluate the diagnostic performance of this simplified strategy, compared with the complete test, in our population with a low prevalence of gestational diabetes. DESIGN: We collected 2298 complete 75-g glucose tolerance tests. We simulated stopping the test, so avoiding the glucose loading and further glycaemia, if fasting glycaemia was <4.4 or >=5.1 mmol/l. SETTING AND POPULATION: Unselected pregnant women from Geneva and Basel, at 24-28 weeks of gestation. METHODS: We calculated the sensitivity, and the percentage of women who would avoid the complete test with the strategy based on fasting glycaemia. RESULTS: The prevalence of gestational diabetes was 10.9% in our population. Among 251 women with gestational diabetes, fasting glycaemia was >=5.1 mmol/l in 119 women (47.4%), between 4.4 and <5.1 mmol/l in 78 women (31.1%) and <4.4 mmol/l in 54 women (21.5%). Proceeding with the complete test only in women with fasting glycaemia between 4.4 and <5.1 mmol/l will result in a sensitivity of 78.5%. This strategy would avoid glucose loading in 63.8% of women. CONCLUSIONS: Screening with fasting glycaemia is an attractive alternative to universal screening with the complete 75-g glucose tolerance test. This strategy is, however, slightly less sensitive than previously reported in higher-risk populations. TWEETABLE ABSTRACT: Fasting glycaemia can be considered as an alternative to the complete test for gestational diabetes screening. PMID- 26810792 TI - Volatile emissions during storing of green food waste under different aeration conditions. AB - Controlled field experiments were carried out for monitoring the emissions of three plastic commercial household waste bins, which were adapted for studying the effect of aeration process in the evolved volatiles, during house storing of green food waste for 2 weeks, prior to collection. Three experimental scenarios were examined based on no aeration ("NA," closed commercial waste bin), diffusion based aeration ("DA," closed commercial waste bin with tiny holes), and enforced aeration ("EA," closed commercial waste bin with tiny holes and enforced aeration). The monitoring of volatile organic compounds (VOCs) emitted from organic household kitchen waste was performed using solid-phase microextraction gas chromatography-mass spectrometry (SPME-GC-MS) analysis. Portable sensors were also used for monitoring selected gases and parameters of environmental, bioprocess, and health interest (e.g., CO2, O2, H2S, CH4, NH3, % RH, waste temperatures). VOC emissions are strongly dependent on the waste material. The most frequent VOCs identified over the storing waste, showing over 50 % appearance in all examined samples, were terpenes (e.g., di-limonene, beta myrcene, delta-3-carene, alpha-pinene, alpha-terpinolene, linalool, etc.), sulfides (dimethyl disulfide), aromatics (benzene, 1-methyl-2-(2-propenyl)), alkanes (e.g., decane, dodecane), ketones (2-propanone), esters (e.g., acetic acid ethyl ester, acetic acid methyl ester), and alcohols (e.g., 3-cyclohexen-1 ol, 4-methyl-1-(1-methylethyl)). The prominent role of terpenes in the "pre compost" odor and especially that of di-limonene was highlighted. In all examined scenarios, the emitted volatiles were increased at raised temperatures and later decreased in time. Aeration of waste bins slightly affected the volatilization process resulting in higher profiles of VOCs; uniformity in the composition of VOCs was also noted. Slight modifications of commercial waste bins may favor the initiation of home composting. PMID- 26810796 TI - Uptake of 2,4-bis(Isopropylamino)-6-methylthio-s-triazine by Vetiver Grass (Chrysopogon zizanioides L.) from Hydroponic Media. AB - 2,4-bis(Isopropylamino)-6-methylthio-s-triazine (prometryn) poses a risk to aquatic environments in several countries, including China, where its use is widespread, particularly due to its chemical stability and biological toxicity. Vetiver grass (Chrysopogon zizanioides L.) was tested for its potential for phytoremediation of prometryn. Vetiver grass was grown in hydroponic media in a greenhouse, in the presence of prometryn, with appropriate controls. Plant uptake and removal of prometryn from the media were monitored for a period of 67 days. The results showed that the removal of the prometryn in the media was expedited by vetiver grass. The removal half-life (t1/2) was shortened by 11.5 days. Prometryn removal followed first-order kinetics (Ct = 1.8070e(-0.0601t)). This study demonstrated the potential of vetiver grass for the phytoremediation for prometryn. PMID- 26810799 TI - Successful cuing of gender source memory does not improve location source memory. AB - In three experiments we explored cross-dimensional cuing effects in a multidimensional source encoding and retrieval paradigm. We employed a bias controlled experimental method of source cuing at retrieval (Starns & Hicks, 2013) in an attempt to improve retrieval of location information indirectly by cuing gender information. Encoded words were situated on the left or right side of a computer monitor and associated with either a male or a female face. When multiple faces were used across the set of encoded words, reinstating the correct face at retrieval alongside an incorrect, opposite-gender face cue improved male/female source decisions for test words. However, this powerful test cue did not improve memory for the encoded location of the words, suggesting that within dimension cuing does not produce cross-dimensional cuing. This null outcome was found when gender decisions were required (Experiments 1A and 2) or not required (Experiment 1B) prior to location decisions. Nor was cross-dimension cuing found when subjects were told to expect a source test of both gender and location information at retrieval (Experiment 2). Our findings reinforce prior work demonstrating that multiple context dimensions can be bound to item information without any direct binding between the contexts. PMID- 26810801 TI - Micro scale self-interaction chromatography of proteins: A mAb case-study. AB - Self-interaction chromatography is known to be a fast, automated and promising experimental technique for determination of B22, but with the primary disadvantage of needing a significant amount of protein (>50 mg). This requirement compromises its usage as a technique for the early screening of new biotherapeutic candidates. A new scaled down SIC method has been evaluated here using a number of micro LC columns of different diameters and lengths, using typically 10 times less stationary phase than traditional SIC. Scale-down was successfully accomplished using these micro-columns, where the SIC results for a range of differing columns sizes were in agreement, as reflected by k', B22 and column volumes data. The results reported here demonstrate that a scaled down version of SIC can be easily implemented using conventional liquid chromatography system where the final amount of mAbs used was 10 times less than required by conventional SIC methodologies. PMID- 26810800 TI - Screening Platform toward New Anti-HIV Aptamers Set on Molecular Docking and Fluorescence Quenching Techniques. AB - By using a new rapid screening platform set on molecular docking simulations and fluorescence quenching techniques, three new anti-HIV aptamers targeting the viral surface glycoprotein 120 (gp120) were selected, synthesized, and assayed. The use of the short synthetic fluorescent peptide V35-Fluo mimicking the V3 loop of gp120, as the molecular target for fluorescence-quenching binding affinity studies, allowed one to measure the binding affinities of the new aptamers for the HIV-1 gp120 without the need to obtain and purify the full recombinant gp120 protein. The almost perfect correspondence between the calculated Kd and the experimental EC50 on HIV-infected cells confirmed the reliability of the platform as an alternative to the existing methods for aptamer selection and measuring of aptamer-protein equilibria. PMID- 26810802 TI - Deep eutectic solvents in countercurrent and centrifugal partition chromatography. AB - Deep eutectic solvents (DESs) were evaluated as solvents in centrifugal partition chromatography, a liquid-liquid chromatography separation technology. To this end, the partition coefficients of ten natural compounds of different hydrophobicity were determined in non-aqueous biphasic systems containing DES. The influence of the composition of DESs and the presence of water in the biphasic system on the partition coefficient were also examined. In addition, several process relevant physical properties of the biphasic system, such as the density and viscosity of the phases, were measured. A mixture of three to four hydrophobic compounds was successfully separated in a centrifugal partition extractor using a heptane/ethanol/DES biphasic system. PMID- 26810803 TI - Design and evaluation of microfluidic devices for two-dimensional spatial separations. AB - Various designs of chips for comprehensive two-dimensional spatial liquid chromatography were investigated. The performance of these chips was initially evaluated using computational fluid dynamics (CFD). A bifurcating distributor with an angle of 140 degrees between branches was implemented in order to achieve a homogeneous velocity field. The cross-sectional area of the channels of the flow distributor was fixed at 0.5 * 0.5 mm, which allows a robust micromilling technique to be used for chip manufacturing. Experiments were performed with chips featuring purposely introduced imperfections in the structure of the bifurcating flow distributor to study its capacity of overcoming potential local clogging. Split peaks were observed when 75% of one of the flow channels was obstructed, in line with the CFD predictions. The main bottlenecks for the performance of the spatial two-dimensional chips were identified, viz. sample injected in the first dimension diverging into the flow distributor and channel discretization (i.e., remixing of first-dimension separation peaks because of finite number of second-dimension channels). Solutions to the former problem were studied by applying a flow resistance in the vertical segments that formed the outlets of the flow distributor and by simulating the presence of constrictions. It was found that a flow resistance of 1.0*10(11) m(-2) reduced the amount of sample diverging into the flow distributor by a factor of 10. The presence of a constriction of 90% of the segment area and 50% of the segment length decreased the diverging flow by a factor of 5. The influence of the linear velocity was significant. Solutions to the channel discretization problem were sought by investigating different designs of spatial two-dimensional chips. PMID- 26810804 TI - Evaluation of the matrix effect on gas chromatography--mass spectrometry with carrier gas containing ethylene glycol as an analyte protectant. AB - The consequences of matrix effects in GC are a major issue of concern in pesticide residue analysis. The aim of this study was to evaluate the applicability of an analyte protectant generator in pesticide residue analysis using a GC-MS system. The technique is based on continuous introduction of ethylene glycol into the carrier gas. Ethylene glycol as an analyte protectant effectively compensated the matrix effects in agricultural product extracts. All peak intensities were increased by this technique without affecting the GC-MS performance. Calibration curves for ethylene glycol in the GC-MS system with various degrees of pollution were compared and similar response enhancements were observed. This result suggests a convenient multi-residue GC-MS method using an analyte protectant generator instead of the conventional compensation method for matrix-induced response enhancement adding the mixture of analyte protectants into both neat and sample solutions. PMID- 26810805 TI - A method for the determination of fullerenes in soil and sediment matrices using ultra-high performance liquid chromatography coupled with heated electrospray quadrupole time of flight mass spectrometry. AB - The increasing production of fullerenes likely means a release of these chemicals in the environment. Since soils and sediments are expected to act as a sink, analytical tools are needed to assess the presence of fullerenes in these matrices. In the present work, a method was developed for the determination of fullerenes at environmental relevant levels employing Ultra High Performance Liquid Chromatograph coupled with High Resolution Mass Spectrometry (UHPLC-HRMS). Chromatographic separation was achieved with a core-shell biphenyl stationary phase that provided fast analysis with complete baseline separation. Ion Booster Electro Spray Ionization (IB-ESI) resulted in higher ionization efficiency and was much less susceptible to adduct formation in comparison with standard ESI, whereas Quadrupole Time of Flight (QTOF) MS granted high resolution mass spectra used for accurate identification. The Instrumental method limits of detection (ILoD) and quantification (ILoQ) were 6 and 20 fg, respectively, for C60 and 12 and 39 fg, respectively, for C70. Matrix effects related to co-extractants were systematically investigated in soil and sediments extracts through standard addition method (SAM) and monitoring the signal response during the chromatographic run of these samples. Consequently, minor chromatographic modifications were necessary for the analysis of matrices with high organic carbon content. The method limit of detection (MLoD)ranged from 84 pg/kg to 335 pg/kg, whereas limit of quantification (MLoQ) ranged from 279 pg/kg to 1.1 ng/kg. Furthermore, the method was successfully applied for the analysis of functionalized fullerenes (i.e. methanofullerenes). To the best of our knowledge, this is the first analytical method for the analysis of fullerenes in soils and sediments that employ core-shell biphenyl stationary phase as well as IB-ESI-QTOF MS hyphenated with UHPLC. PMID- 26810806 TI - Purification of single-chain antibody fragments exploiting pH-gradients in simulated moving bed chromatography. AB - This paper deals with the theoretical design and experimental validation of an affinity-based continuous multi-column chromatography process for the purification of single-chain Fragment variable (scFv) antibodies. An open-loop 3 zone pH-gradient simulated moving bed (SMB) process was investigated exploiting the highly specific affinity of metal ions toward histidine-tagged recombinant proteins. The separation problem was simplified by considering the cell culture supernatant as a pseudo-binary mixture. The influence of mobile phase pH on the adsorption isotherm parameters was estimated by the inverse method using recorded pH-gradient batch elution profiles. Suitable operating parameters for the SMB process were identified using an equilibrium stage model and subsequently validated in a lab-scale SMB unit. Finally, the performance of the pH-gradient SMB process was compared against a non-optimized batch process. Biologically active single-chain Fragment variable antibody formats were purified continuously with 9% more recovery, 11 times more productivity (576 mg of purified scFv per day and liter stationary phase in SMB) and enriched by a factor of 2.5 compared to those obtained in the non-optimized batch process. PMID- 26810807 TI - Water-compatible temperature and magnetic dual-responsive molecularly imprinted polymers for recognition and extraction of bisphenol A. AB - Versatile molecularly imprinted polymers (MIPs) have been widely applied to various sample matrices, however, molecular recognition in aqueous media is still difficult. Stimuli-responsive MIPs have received increasing attentions due to their unique feature that the molecular recognition is regulated by specific external stimuli. Herein, water-compatible temperature and magnetic dual responsive MIPs (WC-TMMIPs) with hydrophilic brushes were prepared via reversible addition-fragmentation chain transfer precipitation polymerization for reversible and selective recognition and extraction of bisphenol A (BPA). Transmission electron microscopy (TEM), Fourier transform infrared spectrometer (FT-IR) and vibrating sample magnetometry (VSM) as characterization methods were used to examine the successful synthesis of polymers, and the resultant WC-TMMIPs showed excellent thermosensitivity and simple rapid magnetic separation. Controlled adsorption and release of BPA by temperature regulation were investigated systematically, and the maximum adsorption and removal efficiency toward BPA in aqueous solutions were attained at 35 degrees C and 45 degrees C, respectively, as well as a good recoverability was exhibited with the precision less than 5% through five adsorption-desorption cycles. Phenolic structural analogs were tested and good recognition specificity for BPA was displayed. Accordingly, the WC-TMMIPs were employed as adsorbents for magnetic solid-phase extraction (MSPE) and packed SPE of BPA from seawater samples. Using the two modes followed by HPLC UV determination, excellent linearity was attained in the range of 0.1-14.5 MUM and 1.3-125 nM, with low detection limits of 0.02 MUM and 0.18 nM, respectively. Satisfactory recoveries for spiked seawater samples were achieved ranging from 86.3-103.5% and 96.2-104.3% with RSD within 2.12-4.33%. The intelligent WC-TMMIPs combining water-compatibility, molecular recognition, magnetic separation, and temperature regulation proved potentially applicable for selective identification, controlled adsorption/release and high-efficiency enrichment/removal of trace targets in complicated aqueous media. PMID- 26810808 TI - Core-shell electrospun polybutylene terephthalate/polypyrrole hollow nanofibers for micro-solid phase extraction. AB - In the present work, a new micro-solid phase extraction (MU-SPE) sorbent as an extracting medium based on core-shell nanofibers was synthesized by electrospinning. The core-shell nanofibers of polyvinylpyrrolidone-Polybutylene terephthalate/polypyrrole (PVP-PBT/PPy) were electrospun and subsequently, modified hollow nanofibers were prepared by removing the central PVP moiety. Moreover, conventional PBT/PPy was also prepared for the comparison purposes. The homogeneity and the porous surface structure of the core-shell nanofibers were confirmed by scanning electron microscopy (SEM). The applicability of the fabricated nanofibers-coating was examined by immersed MU-SPE of some selected triazine herbicides from aqueous samples and wheat grains. Subsequently, the extracted analytes were transferred into a gas chromatography (GC) after solvent desorption. Influencing parameters on the morphology of nanofiber such as elctrospinning parameters and the weight ratio of components were optimized. In addition, effects of different parameters influencing the extraction efficiency including extraction temperature, extraction time, ionic strength, sample pH, desorption temperature, and desorption time were investigated and optimized. Eventually, the developed method was validated by gas chromatography-mass spectrometry (GC-MS). At the optimum conditions, the relative standard deviation values for real water samples spiked with the selected triazines at 1 ng mL(-1) were 4-8% (n=3) and the limits of detection for the studied compounds were between 50 and 90 ng L(-1). The calibration curves for the selected triazines were in the range of 0.3-500 ng mL(-1) and regression coefficients (R(2)) were between 0.9985 and 0.9996. PMID- 26810809 TI - Simultaneous qualitative and quantitative analysis of fluoroalkyl sulfonates in riverine water by liquid chromatography coupled with Orbitrap high resolution mass spectrometry. AB - In this study, a robust method for quick screening, confirmation and quantification analysis of eight fluoroalkyl sulfonates in surface riverine samples was developed using ultra-high performance liquid chromatography-high resolution mass spectrometer (LC-Orbitrap Tribrid HRMS). Weak anion exchange solid phase extraction was optimized to maximum recover perfluoroalkyl sulfonates (PFSAs), fluorotelomer sulfonates and the emerging 6:2 chlorinated polyfluoroalkyl ether sulfonate at the same time. Both qualitative and quantitative purposes could be achieved by simultaneous acquiring full-scan mass spectrum (MS(1)) and data-dependent MS(2) data. The LC-Orbitrap Tribrid HRMS method showed competent method detection limits for all analytes (7.1-62 pg/L) compared with the triple quadrupole mass spectrometry (LC-MS/MS) quantification method (12-54 pg/L), and satisfactory method validation results were also obtained in linearity (R(2)>0.999), trueness (88-118%), precision (2-17%) and recovery (63-103%). A good correlation (R>0.999) was found between the sets of quantified PFSA residue concentrations in thirteen estuary river samples by both the LC-Orbitrap Tribrid HRMS (0.2-440 ng/L) and LC-MS/MS (0.1-424 ng/L) methods, indicating that Orbitrap Tribrid HRMS could be used for reliable quantitative analysis purpose. Moreover, the LC-Orbitrap Tribrid HRMS method could also benefit from its high mass resolution characteristic to eliminate potential environment interferents (e.g., taurodeoxycholate) and to quantify all PFSA isomers based on full-scan MS(1) chromatogram at a narrow MS window (5 part per million). PMID- 26810811 TI - Ameliorative and antioxidant effects of myrtle berry seed (Myrtus communis) extract during reflux-induced esophagitis in rats. AB - Context Myrtle, Myrtus communis L. (Myrtaceae), is a medicinal plant well known for its richness in phenolic compounds and its beneficial effects for the treatment of gastrointestinal disorders. Objective In the present work, the protective effect of the myrtle berry seed aqueous extract (MBSAE) against esophageal reflux (ER)-induced damage in esophagus mucosa as well as the mechanisms implicated was determined. Materials and methods In this respect, adult male Wistar rats were used and divided into seven groups: Control, ER, ER + various doses of MBSAE, ER + famotidine or ER + gallic acid. The ER was induced and animals were per orally (p.o.) treated with MBSAE or reference molecules during 6 h. The phytochemical screening was determined using colourimetric analysis. Results MBSAE is rich in total polyphenols and anthocyanins and exhibited an important in vitro antioxidant activity. In vivo, we firstly found that ER led to marked macroscopic and histopathological changes in esophagus. The results showed, also, that the ER was accompanied by a state of oxidative stress as assessed by an increase of lipid peroxidation, a decrease of the sulphhydryl groups and glutathione levels, as well as antioxidant enzyme activities depletion. MBSAE abrogated all morphological, histopathological and biochemical alterations. We showed also that ER increased esophageal calcium, hydrogen peroxide (H2O2) and free iron levels while MBSAE treatment protected against intracellular mediators deregulation. Conclusion Our data suggest that MBSAE exerted a potential protective effect against ER-induced damage in rat esophagus, at least in part, due to its antioxidant properties. PMID- 26810812 TI - The potential of DISC1 protein as a therapeutic target for mental illness. PMID- 26810813 TI - A model-based evaluation of single metrics for discriminating changes in rheumatoid arthritis disease activity. AB - AIMS: Composite indices for quantifying rheumatoid arthritis (RA) disease activity such as the 28-joint disease activity score (DAS28) are comprised of single parameters ('metrics') in various combinations. Population modelling methods were used to evaluate single metrics for their ability to reflect changes in disease activity with a view to understanding and improving composite indices. METHODS: A total of 11 single metrics of RA disease activity (tender and swollen joint counts, acute phase reactants and global health, pain and physical function assessments) were obtained from 203 patients with recent onset RA. Participants received combination disease-modifying anti-rheumatic drugs (DMARDs) according to a treat-to-target approach with a pre-defined protocol for treatment intensification. Models describing each metric's magnitude and variability of change from baseline to a single 'treated' state in the population were developed using nonmem((r)) . Measures that displayed uniformly large changes between states across the population were ranked higher in terms of discriminatory capacity. RESULTS: Joint counts demonstrated a greater ability to discriminate changes in RA disease activity than others. Correlations between metrics demonstrated that erythrocyte sedimentation rate (ESR) had limited relationships with others for baseline scores and changes in RA disease activity (r generally < 0.2). However it appeared to be important in describing changes for those individuals where ESR levels were initially elevated. CONCLUSION: It appears unlikely that a single group of metrics may be suitable to capture disease activity changes across all RA patients and defining the most appropriate metric(s) for individual patients will be an important area of future research. PMID- 26810814 TI - 2015 ACR/ACC/AHA/AATS/ACEP/ASNC/NASCI/SAEM/SCCT/SCMR/SCPC/SNMMI/STR/STS Appropriate Utilization of Cardiovascular Imaging in Emergency Department Patients With Chest Pain: A Joint Document of the American College of Radiology Appropriateness Criteria Committee and the American College of Cardiology Appropriate Use Criteria Task Force. PMID- 26810815 TI - National Institutes of Health Perspective on Reports of Gadolinium Deposition in the Brain. PMID- 26810816 TI - Estimating the risks of faecal transplants. PMID- 26810818 TI - SATB1 expression is correlated with beta-catenin associated epithelial mesenchymal transition in colorectal cancer. AB - SATB1, a global gene regulator, has been implicated in the growth and metastasis of multiple cancers, including colorectal cancer. While the understanding about the role of SATB1 in CRC remains limited. The aim of our study is to investigate the expression of SATB1 in CRC, and the relationship between SATB1 expression pattern and clinicopathological variables. A further aim is to analyze the correlation between SATB1 expression and epithelial-mesenchymal transition in CRC. Immunohistochemical expression of SATB1, beta-catenin, E-cadherin, CK20, Vimentin, SMA, and desmin were assessed in a cohort of 200 patients using tissue microarrays. SATB1 was expressed in 133 (66.5%) CRC primary lesions, 14 (28%) adjacent colorectal mucosa specimens, and 60 (75%) corresponding lymph node metastases. The expression level of SATB1 was significantly higher in lymph node metastases than in CRC primary lesions and normal mucosa (P = 0.000). High expression of SATB1 in CRC was strongly correlated with poor differentiation of tumor tissues (P = 0.000). High expression of SATB1 was significantly correlated with aberrant expression of beta-catenin (P = 0.0005), low expression of E cadherin (P = 0.000) and CK20 (P = 0.000) and with high expression of Vimentin (P = 0.001). No SMA or desmin protein was expressed in the CRC cells. Our results suggested that high expression of SATB1 is significantly correlated with poor differentiation of CRC. SATB1 might promote the epithelial-mesenchymal transition by increasing the aberrant expression of beta-catenin. PMID- 26810819 TI - The first catalytic asymmetric thioacetalization by chiral phosphoric acid catalysis. AB - We report here the first catalytic asymmetric thioacetalization of salicylaldehyde and dithiol. Chiral phosphoric acid STRIP C5 is identified as a powerful catalyst for this reaction to afford various chiral dithioacetals in high to excellent yields and enantioselectivities under mild conditions. PMID- 26810823 TI - Timing of ankle motion and trunk velocity during sit-to-stand in healthy young subjects. PMID- 26810824 TI - Safety and Efficacy of Operative Versus Nonsurgical Management of Distal Radius Fractures in Elderly Patients: A Systematic Review and Meta-analysis. AB - PURPOSE: To assess the safety and efficacy of operative versus nonsurgical treatment of distal radius fractures in elderly patients. METHODS: We comprehensively searched the PubMed, Web of Science, and Cochrane Library databases for studies that satisfied predetermined inclusion and exclusion criteria. Outcomes of interest included pain level, grip strength, wrist range of motion, wrist functional assessment, radiographic parameters, and complications; we compared these using continuous measurements. We performed a systematic review and meta-analysis to assess operative versus nonsurgical procedures in patients aged 60 years and older. RESULTS: Two randomized controlled trials and 6 retrospective studies were included. Meta-analysis did not detect statistically significant differences in pooled data for pain level, functional assessment, and wrist range of motion between the operative and nonsurgical groups. Grip strength was significantly greater in the operative group. The incidence of major complications requiring surgery and that of tendon injury were significantly higher in the operative group. Radiographic outcomes including volar tilt, radial inclination, and ulnar variance were significantly better in the operative group. Considerable heterogeneity was present in all studies and adversely affected the precision of the meta-analysis. CONCLUSIONS: The current literature does not support the theory that operative management can provide better clinical outcomes for elderly patients with distal radius fractures. Although operative management can offer better radiographic outcomes and grip strength than can nonsurgical treatment, the risk of complications requiring surgical treatment is greater. Thus, indications for operative fixation should be considered carefully in the treatment of elderly patients. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III. PMID- 26810820 TI - Complex formation and turnover of mitochondrial transporters and ion channels. AB - Mitochondria are responsible for many vital cellular functions in eukaryotic cells, such as ATP production, steroid synthesis and prosthetic group biogenesis. The vital functions of mitochondria are possible due to the compartmental nature of this organelle. Mitochondria form a dynamic network that can exist as a network throughout a cell or as distinct individual structures. Mitochondria are also composed of two membranes, an inner and outer membrane. The inner mitochondrial membrane (IMM) is significantly larger than the outer membrane and must fold upon itself to be contained within the outer mitochondrial membrane (OMM). These folds are known as cristae. Altogether these different membrane compartments specialize in different functions of the mitochondria. The OMM is responsible for passage of small metabolites into and out of the mitochondria while excluding macromolecules. The IMM is a highly selective barrier between the solutes of the cytosol and those within the mitochondrial matrix. Cristae specialize in oxidative phosphorylation. The functions of these membranes are afforded by membrane proteins that are able to transport specific solutes. The appropriate localization, assembly into multi-subunit protein complexes, and wild type function of these membrane proteins therefore is vital for mitochondria to maintain appropriate function and support cellular survival. This review will address the composition and functions of mitochondrial membrane localized multi subunit protein complexes along with how these proteins undergo degradation to maintain homeostatic functions of mitochondria in the context of mitochondria specific transporters and ion channels. Due to the large number of known mitochondrial membrane transporters and ion channels this review will focus on the topics presented at the Mitochondrial Ion Channels and Transporters Symposium hosted by the New York University College of Dentistry in September 2015 in honor of Casey Kinnally. PMID- 26810825 TI - Dorsal Radiotriquetral Ligament Snapping Wrist Syndrome - A Novel Presentation and Review of Literature: Case Report. AB - We report 2 cases of audible intrinsic wrist snapping without a palpable click resulting from dorsal radiotriquetral ligament adhesions. After its debridement, both patients demonstrated complete resolution of symptoms. PMID- 26810827 TI - Assessment and Planning for a Pediatric Bilateral Hand Transplant Using 3 Dimensional Modeling: Case Report. AB - Children are not typically considered for hand transplantation for various reasons, including the difficulty of finding an appropriate donor. Matching donor recipient hands and forearms based on size is critically important. If the donor's hands are too large, the recipient may not be able to move the fingers effectively. Conversely, if the donor's hands are too small, the appearance may not be appropriate. We present an 8-year-old child evaluated for a bilateral hand transplant following bilateral amputation. The recipient forearms and model hands were modeled from computed tomography imaging studies and replicated as anatomic models with a 3-dimensional printer. We modified the scale of the printed hand to produce 3 proportions, 80%, 100% and 120%. The transplant team used the anatomical models during evaluation of a donor for appropriate match based on size. The donor's hand size matched the 100%-scale anatomical model hand and the transplant team was activated. In addition to assisting in appropriate donor selection by the transplant team, the 100%-scale anatomical model hand was used to create molds for prosthetic hands for the donor. PMID- 26810826 TI - Accuracy and Validity of Goniometer and Visual Assessments of Angular Joint Positions of the Hand and Wrist. AB - PURPOSE: To compare goniometric and visual assessments of angular hand joint and wrist joint positions measured by board-certified hand surgeons and certified hand therapists. We hypothesized that visual estimation would be similar to the goniometric measurement accuracy of digital and wrist joint positions. METHODS: The wrist, index finger metacarpophalangeal (MCP) joint, and index finger proximal interphalangeal (PIP) joint were evaluated in different positions by 40 observers: 20 board-certified hand surgeons and 20 certified hand therapists. Each observer estimated the position of the wrist, index MCP joint, and index PIP joint of the same volunteer, who was positioned in low-profile orthoses to reproduce predetermined positions. Following visual estimation, the participants measured the same joint positions using a goniometer. The control measurement was digitally determined by a radiologist who obtained radiographs of the hand and wrist positions in each orthosis. Observers were blinded to the results of control measurements. RESULTS: When considering all joints at all positions, neither visual assessments nor goniometer assessments were consistently within +/ 5 degrees of the measurements obtained on control radiographs. When considering individual joints, goniometer measurements were significantly closer to control radiograph measurements than the visual assessments for all 3 PIP joint positions. There was no difference for the measurements at the wrist or for 2 of the 3 MCP joint positions. Significant differences between surgeon and therapist joint angle measurements were not observed when comparing visual and goniometer assessments to radiograph controls. CONCLUSIONS: Compared with radiograph measurements, neither visual nor goniometer assessment displayed high levels of accuracy. On average, visual assessment of the angular positions of the index MCP and wrist joint were as accurate as the goniometer assessment, whereas goniometer assessment of the angular position of the PIP joint was more accurate than visual assessment. There was a relatively high degree of between-observer variability in measurements, and therefore, no one person's measurements could be consistently relied upon to be accurate. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II. PMID- 26810828 TI - Development and Validation of a Modified Multiple Errands Test for Adults with Intellectual Disabilities. AB - BACKGROUND: The aims of the current study were to adapt a version of the MET for people with intellectual disabilities and assess its ecological and construct validity. MATERIAL AND METHODS: Using a correlational design, 40 participants with intellectual disabilities were invited to complete a battery of neuropsychological assessments and the modified Multiple Errands Test for Intellectual Disabilities (mMET-IDs). RESULTS: The ability to successfully complete tasks on the mMET-IDs correlated significantly with measures of the Supervisory Attentional System, namely, the Tower of London Test and the Six Parts Test. However, performance on the mMET-IDs and the Six Parts Test could be accounted for by Verbal IQ and receptive vocabulary. The mMET-IDs failed to correlate with the DEX-IR. CONCLUSIONS: The mMET-IDs can be successfully used to assess some aspects of the Supervisory Attentional System in people with intellectual disabilities. Further development is needed, however, to improve the ecological validity of the mMET-IDs. PMID- 26810829 TI - Uterine blood flow evaluation in bitches suffering from cystic endometrial hyperplasia (CEH) and CEH-pyometra complex. AB - Doppler ultrasound is a useful diagnosis tool to evaluate uterine blood flow in different canine reproductive states. The aim of this study was to describe and compare uterine blood flow in bitches suffering from cystic endometrial hyperplasia (CEH) and CEH-pyometra complex (CEH-P). Ninety diestrous bitches were clinically, hematologically, and ultrasonographically classified into four groups: (1) clinical signs, leukocytosis, CEH, and uterine luminal contents (CEH P, n = 31); (2) asymptomatic bitches with CEH and uterine contents (CEH-C, n = 15); (3) asymptomatic bitches with CEH without uterine contents (CEH, n = 16); and (4) normal diestrous bitches (ND, n = 28). The widest cross-sectional diameter and uterine wall thickness (W) of uterine horns were measured using two dimensional ultrasound. Peak systolic velocity and end diastolic velocity of uterine arteries were measured by Doppler ultrasound in all the bitches. Peak systolic velocity and end diastolic velocity were higher in CEH-P than in CEH-C, CEH, and ND (P < 0.01); although both parameters did not show differences among the latter three groups (P > 0.1). Conversely, resistance index (RI) reported lower values in CEH-P than that in the other three groups (P < 0.01), being ND higher (P < 0.01) than both CEH-C and CEH which did not differ between themselves (P > 0.1). When all the bitches were considered, correlation between RI and cross sectional diameter was r = -0.69 (P < 0.01) and between RI and uterine wall thickness was r = -0.02 (P > 0.1). It is concluded that the uterine artery blood flow velocity of bitches suffering from pyometra was higher, not only from normal bitches, but also from females with endometrial hyperplasia. Furthermore, endometrial hyperplasia, accompanied or not by luminal contents, had a higher blood flow velocity than normal uterus. Hemodynamic parameters appear as useful markers to differentiate uterine pathologic conditions. PMID- 26810830 TI - Effect of Pseudomonas aeruginosa on sperm capacitation and protein phosphorylation of boar spermatozoa. AB - Several studies have reported the detrimental effects that bacteriospermia causes on boar sperm quality, but little is known about its effects on IVC. Considering that, the present study sought to evaluate the effects of different concentrations of Pseudomonas aeruginosa on different indicators of capacitation status (sperm viability, membrane lipid disorder, sperm motility kinematics, and protein phosphorylation of boar spermatozoa) after IVC. Flow cytometry and computer assisted sperm analysis (CASA) revealed that the presence of P aeruginosa in boar sperm samples, mostly at concentrations greater than 10(6) CFU/mL, is associated with a significant (P < 0.05) decrease in the percentages of both sperm membrane integrity and sperm with low membrane lipid disorder, and also with a reduction in sperm motility kinetic parameters when compared with results obtained from the control sample, which presented the typical motility pattern of capacitated-like boar spermatozoa. Moreover, Western blot results also showed significant (P < 0.05) changes in the levels of tyrosine, serine, and threonine protein phosphorylation because of bacterial contamination, the decrease in phosphotyrosine levels of p32, a well-known marker of IVC achievement in boar sperm, being the most relevant. Indeed, after 3 hours of IVC, phosphotyrosine levels of p32 in the control sample were 3.13 +/- 0.81, whereas in the tubes with 10(6) and 10(8) CFU/mL were 1.05 +/- 0.20 and 0.36 +/- 0.07, respectively. Therefore, the present study provides novel data regarding the effects of bacterial contamination on boar sperm, suggesting that the presence of P aeruginosa affects the fertilizing ability of boar sperm by altering its ability to accomplish IVC. PMID- 26810831 TI - The effect of puerperal uterine disease on histopathologic findings and mRNA expression of proinflammatory cytokines of the endometrium in dairy cows. AB - The aim of this study was to investigate the effect of puerperal uterine disease on histopathologic findings and gene expression of proinflammatory cytokines in the endometrium of postpuerperal dairy cows; 49 lactating Holstein-Friesian cows were divided into two groups, one without (UD-; n = 29) and one with uterine disease (UD+; n = 21), defined as retained fetal membranes and/or clinical metritis. General clinical examination, vaginoscopy, transrectal palpation, and transrectal B-mode sonography were conducted on days 8, 11, 18, and 25 and then every 10 days until Day 65 (Day 0 = day of calving). The first endometrial sampling (ES1; swab and biopsy) was done during estrus around Day 42 and the second endometrial sampling (ES2) during the estrus after synchronization (cloprostenol between days 55 and 60 and GnRH 2 days later). The prevalence of histopathologic evidence of endometritis, according to the categories used here, and positive bacteriologic cultures was not affected by group (P > 0.05), but cows with uterine disease had a higher prevalence of chronic purulent endometritis (ES1; P = 0.07) and angiosclerosis (ES2; P <= 0.05) than healthy cows. Endometrial gene expression of IL1alpha (ES2), IL1beta (ES2), and TNFalpha (ES1 and ES2) was higher (P <= 0.05) in the UD+ group than in the UD- group. In conclusion, puerperal uterine disease had an effect on histopathologic parameters and on gene expression of proinflammatory cytokines in the endometrium of postpuerperal cows, indicating impaired clearance of uterine inflammation in cows with puerperal uterine disease. PMID- 26810832 TI - Investigating molecular dynamics-guided lead optimization of EGFR inhibitors. AB - The epidermal growth factor receptor (EGFR) is part of an extended family of proteins that together control aspects of cell growth and development, and thus a validated target for drug discovery. We explore in this work the suitability of a molecular dynamics-based end-point binding free energy protocol to estimate the relative affinities of a virtual combinatorial library designed around the EGFR model inhibitor 6{1} as a tool to guide chemical synthesis toward the most promising compounds. To investigate the validity of this approach, selected analogs including some with better and worse predicted affinities relative to 6{1} were synthesized, and their biological activity determined. To understand the binding determinants of the different analogs, hydrogen bonding and van der Waals contributions, and water molecule bridging in the EGFR-analog complexes were analyzed. The experimental validation was in good qualitative agreement with our theoretical calculations, while also a 6-dibromophenyl-substituted compound with enhanced inhibitory effect on EGFR compared to the reference ligand was obtained. PMID- 26810833 TI - Synthesis and anti-tuberculosis activity of glycitylamines. AB - A series of glycitylamines, which were prepared in few steps from readily available carbohydrates, were tested for their ability to inhibit tuberculosis growth in an Alamar Blue BCG colourimetric assay. Several derivatives, including (2R,3R)-1-(hexadecylamine)pent-4-ene-2,3-diol, (2R,3R)-1 (hexadecylmethylamino)pent-4-ene-2,3-diol and 5-deoxy-5-hexadecylmethylamino-D arabinitol, were prepared in good to excellent (44-90%) overall yield and exhibited micromolar (20-41MUM) inhibitory activity that was similar to the first line tuberculosis (TB) drug ethambutol (39MUM) in the same assay. The ease and low cost of the synthesis of the glycitylamines offers definite advantages for their use as potential TB drugs. PMID- 26810834 TI - Semisynthetic routes to PF1022H--A precursor for new derivatives of the anthelmintic cyclooctadepsipeptide PF1022A. AB - The cyclooctadepsipeptide PF1022A and its semisynthetic, commercial analogue emodepside show excellent anthelmintic properties. Bis-hydroxy PF1022 (PF1022H), a minor fermentative side-product represents an interesting precursor for new PF1022 related anthelmintics. We report herein two complementary routes which allow a highly efficient conversion of PF1022A to a regioisomeric mixture consisting mainly of the bis-para isomer PF1022H and the meta-para analogue. PMID- 26810835 TI - Novel triazolothiadiazines act as potent anticancer agents in liver cancer cells through Akt and ASK-1 proteins. AB - Newly designed triazolothiadiazines incorporating with structural motifs of nonsteroidal analgesic anti-inflammatory drugs were synthesized and screened for their bioactivity against epithelial cancer cells. Compounds with bioactivities less then ~5MUM (IC50) were further analyzed and showed to induce apoptotic cell death and SubG1 cell cycle arrest in liver cancer cells. Among this group, two compounds (1g and 1h) were then studied to identify the mechanism of action. These molecules triggered oxidative stress induced apoptosis through ASK-1 protein activation and Akt protein inhibition as demonstrated by downstream targets such as GSK3beta, beta-catenin and cyclin D1. QSAR and molecular docking models provide insight into the mechanism of inhibition and indicate the optimal direction of future synthetic efforts. Furthermore, molecular docking results were confirmed with in vitro COX bioactivity studies. This study demonstrates that the novel triazolothiadiazine derivatives are promising drug candidates for epithelial cancers, especially liver cancer. PMID- 26810836 TI - Kinetic and X-ray crystallographic investigations on carbonic anhydrase isoforms I, II, IX and XII of a thioureido analog of SLC-0111. AB - SLC-0111 (4-(4-fluorophenylureido)-benzenesulfonamide) is the first carbonic anhydrase (CA, EC 4.2.1.1) IX inhibitor to reach phase I clinical trials as an antitumor/antimetastatic agent. Here we report a kinetic and X-ray crystallographic study of a congener of SLC-0111 which incorporates a thioureido instead of ureido linker between the two aromatic rings as inhibitor of four physiologically relevant CA isoforms. Similar to SLC-0111, the thioureido derivative was a weak hCA I and II inhibitor and a potent one against hCA IX and XII. X-ray crystallography of its adduct with hCA II and comparison of the structure with that of other five hCA II-sulfonamide adducts belonging to the SLC 0111 series, afforded us to understand the particular inhibition profile of the new sulfonamide. Similar to SLC-0111, the thioureido sulfonamide primarily interacted with the hydrophobic side of the hCA II active site, with the tail participating in van der Waals interactions with Phe131 and Pro202, in addition to the coordination of the deprotonated sulfonamide to the active site metal ion. On the contrary, the tail of other sulfonamides belonging to the SLC-0111 series (2-isopropyl-phenyl; 3-nitrophenyl) were orientated towards the hydrophilic half of the active site, which was correlated with orders of magnitude better inhibitory activity against hCA II, and a loss of selectivity for the inhibition of the tumor-associated CAs. PMID- 26810837 TI - Strongly Enhanced Water Splitting Performance of Ta3 N5 Nanotube Photoanodes with Subnitrides. AB - Subnitrides strongly enhance the efficiency of Ta3 N5 -nanotube photoanodes in photochemical water splitting. The fabrication of Ta3 N5 nanotube layers with a controlled subnitride layer at the interface to the back contact is demonstrated. The insertion of this subnitride layer has a strong influence on the electron transfer to the back contact, and as a result leads to a drastic shift in photocurrent onset potential and a considerable enhancement of photocurrent conversion efficiency. PMID- 26810838 TI - Determinants of pupil diameters and pupil dynamics in an adult Chinese population. AB - BACKGROUND: To investigate the determinants of pupil diameter (PD), amplitude of pupil diameter change (PD-change) and speed of pupil constriction (SPC) using video anterior segment optical coherence tomography (AS-OCT) in a population based sample of Chinese adults. METHODS: Chinese adults aged 40 to 80 years who were free from glaucoma were consecutively recruited from the population-based Singapore Chinese Eye Study. The SPC was measured by AS-OCT videography. Univariate and multivariate analyses were performed to examine the effects of demographic and ocular biometric factors (e.g., axial length [AL], anterior chamber depth [ACD], baseline PD, iris thickness at the area of the dilator muscle [ITDMR], iris area [IA], and iris bowing [IB]) on SPC, PD, and PD-change. RESULTS: A total of 266/302 (89.5 %) AS-OCT videos of eligible eyes were available for analysis. Among these subjects, 64.3 % were women, and the mean age (+/- standard deviation [SD]) was 56 +/- 8.3 years. SPC was not associated with sex. In multiple regression analyses, SPC was independently associated with baseline PD (beta = 0.116, p = 0.006). Baseline PD was independently associated with ACD (beta = 0.341, p < 0.001), TISA 500 (beta = -4.513, p < 0.001), IA (beta = -2.796, p < 0.001), and ITDMR (beta = 6.573, p < 0.001). PD-change was independently associated with ACD (beta = 0.256, p < 0.001), IA (beta = -1.507, p < 0.001), IB (beta = 0.630, p = 0.011), and ITDMR (beta = 3.124, p < 0.001). CONCLUSIONS: Among normal eyes in an adult Chinese population, SPC was associated with larger baseline PD. Larger baseline PD and greater PD change form dark to light were associated with greater ACD, with smaller IA and thicker ITDMR. PMID- 26810843 TI - Single Cell Chemical Proteomics with Membrane-Permeable Activity-Based Probe for Identification of Functional Proteins in Lysosome of Tumors. AB - Proteomics at single-cell resolution can help to identify the heterogeneity among cell populations, shows more and more significance in current chemistry and biology. In this work, we demonstrated a new single cell chemical proteomic (SCCP) strategy with a membrane-permeable activity-based probe (ABP) to characterize the functional proteins in lysosome located in the cytosol. The ABP targeted to the cysteine cathepsin family protein, CpFABP-G, was designed for cysteine cathepsins labeling. The labeled HeLa cell of a cancer cell line was injected into a capillary and was lysed by SDS solution with heating. The lysate was then online readout by capillary electrophoresis-laser-induced fluorescence method. Due to the employment of highly specified ABP kicking out the uncorrelated proteins, the expression of cysteine cathepsins in individual HeLa cells was easily detected, and heterogeneity among those HeLa cells was readily discriminated. Further work was concentrated on SCCP analysis of the mouse leukemia cell of monocyte macrophage (RAW264.7). It was for the first time identifying two expression modes of cysteine cathepsins in RAW264.7, which could be undermined by the analysis of cell populations. We believed that SCCP would be one of the powerful alternatives for proteomics at single-cell resolution. PMID- 26810839 TI - Optimizing Colonoscopy Quality: From Bowel Preparation to Surveillance. AB - OPINION STATEMENT: Colonoscopy is a powerful screening method for colorectal cancer. However, colonoscopy performance is highly variable and quality indicators are needed to ensure delivery of high-quality healthcare. A multi society task force has recently identified three priority quality indicators in colonoscopy: adenoma detection rate, cecal intubation rate, and adherence to surveillance guidelines. The best-studied quality indicator is the adenoma detection rate, which is inversely correlated to the risk of interval colorectal cancer. Other important quality determinants include colonoscopy withdrawal time and the bowel preparation quality. It is important to note that these quality metrics are interrelated and optimization at every level is necessary for any high-quality colorectal cancer screening and prevention program. PMID- 26810844 TI - Age-related Qualitative Histological and Quantitative Stereological Changes in the Equine Pituitary. AB - The aim of this study was to characterize the age-related morphological changes in the equine pituitary and to identify features that allow distinction between pituitary pars intermedia dysfunction (PPID)-associated and non-functional/age associated pars intermedia (PI) adenoma. Pituitary glands of all horses submitted for necropsy examination at the Institute of Veterinary Pathology, Ludwig Maximilians University Munich, between 2008 and 2012 were examined. The pituitary glands of 124 horses were weighed, cut into ~2 mm slices and examined histologically. A slightly modified grading scheme (grades 1-5) was applied to evaluate histological alterations of the PI semiquantitatively. The volume fractions and total volumes of the three pituitary lobes, PI, pars distalis (PD) and pars nervosa (PN), as well as the total number and mean size of PI cells (PICs), were determined using state-of-the-art quantitative stereological methods. There were significant associations between histological grade, the appearance of PI adenomas, follicles and cysts in the PI, lipofuscin in the PN (P <0.001) and focal hyperplasia of chromophobes in the PD and age. In contrast, the appearance of follicles and cysts in the PD, invasion of basophil cells into the PN, haemorrhage and necrosis were not age dependent. PI adenomas were observed in 18% (22/124) of the animals, but only four horses were evidently suffering from PPID, therefore clinically overt/PPID-associated PI adenomas were found in 3% (4/124) of all horses. Most PI adenomas were incidental and considered non functional. Pituitary weight, PI volume, total number and mean volume of PICs increased with age in all horses. The total PI volume and the number of PICs of horses exhibiting PPID-associated PI adenomas were significantly higher, while the mean size of PICs was smaller compared with that of horses showing non-PPID associated adenoma, which suggests that different growth processes are responsible for adenoma formation. The present study demonstrated various age associated lesions of the PD and PN and revealed a high frequency of incidental, non-PPID-associated PI adenomas in aged horses. Therefore, post-mortem diagnosis of PPID in horses is possible, by determination of pituitary weight and by demonstration of PIC hyperplasia, using quantitative stereological methods. PMID- 26810847 TI - Hepatoprotective effects of Flagellaria indica are mediated through the suppression of pro-inflammatory cytokines and oxidative stress markers in rats. AB - Context The antioxidative properties of plants or plant derivative products are well known for their free radical scavenging effects. Flagellaria indica L. (Flagellariaceae) (FI) is a tropical medicinal plant used by the natives of Sabah as medication for semi-paralysis. Objective This study evaluates the hepatoprotective mechanism of FI against carbon tetrachloride (CCl4)-mediated liver damage. Materials and methods Aqueous extract of FI leaves was orally administered to adult Sprague-Dawley rats once daily for 14 consecutive days at 300, 400, and 500 mg/kg b.w. prior to CCl4 treatment (1.0 mL/kg b.w.) on the 13th and 14th days. Results Total phenolic content in the aqueous extract of FI leaves was 65.88 +/- 1.84 mg gallic acid equivalent/g. IC50 value for free radical scavenging activity of FI aqueous extract was reached at the concentration of 400 MUg/mL. Biochemical studies show that the aqueous extract of FI was able to prevent the increase in levels of serum transaminases, alanine aminotransferase, and aspartate aminotransferase (38-74% recovery), and malondialdehyde formation (25-87% recovery) in a dose-dependent manner. Immunohistochemical results evidenced the suppression of oxidative stress markers (4-hydroxynonenal and 8 hydroxydeoxyguanosine) and pro-inflammatory markers (tumour necrosis factor alpha, interleukin-6, prostaglandin E2). Histopathological and hepatocyte ultrastructural alterations proved that there were protective effects in FI against CCl4-mediated liver injury. Signs of toxicity were not present in rats treated with FI alone (500 mg/kg b.w.). Discussion and conclusion It can be concluded that the presence of phenolic constituents and their antioxidative effects can be credited to the hepatoprotective activity of FI. PMID- 26810848 TI - A Shearing-Stretching Device That Can Apply Physiological Fluid Shear Stress and Cyclic Stretch Concurrently to Endothelial Cells. AB - Endothelial cell (EC) morphology and functions can be highly impacted by the mechanical stresses that the cells experience in vivo. In most areas in the vasculature, ECs are continuously exposed to unsteady blood flow-induced shear stress and vasodilation-contraction-induced tensile stress/strain simultaneously. Investigations on how ECs respond to combined shear stress and tensile strain will help us to better understand how an altered mechanical environment affects EC mechanotransduction, dysfunction, and associated cardiovascular disease development. In the present study, a programmable shearing and stretching device that can apply dynamic fluid shear stress and cyclic tensile strain simultaneously to cultured ECs was developed. Flow and stress/strain conditions in the device were simulated using a fluid structure interaction (FSI) model. To characterize the performance of this device and the effect of combined shear stress-tensile strain on EC morphology, human coronary artery ECs (HCAECs) were exposed to concurrent shear stress and cyclic tensile strain in the device. Changes in EC morphology were evaluated through cell elongation, cell alignment, and cell junctional actin accumulation. Results obtained from the numerical simulation indicated that in the "in-plane" area of the device, both fluid shear stress and biaxial tensile strain were uniform. Results obtained from the in vitro experiments demonstrated that shear stress, alone or combined with cyclic tensile strain, induced significant cell elongation. While biaxial tensile strain alone did not induce any appreciable change in EC elongation. Fluid shear stress and cyclic tensile strain had different effects on EC actin filament alignment and accumulation. By combining various fluid shear stress and cyclic tensile strain conditions, this device can provide a physiologically relevant mechanical environment to study EC responses to physiological and pathological mechanical stimulation. PMID- 26810849 TI - The future for Clinical Biomechanics. PMID- 26810850 TI - Genomics: Prediction, Prevention, Priorities, and Punnett. PMID- 26810853 TI - Biologics beyond TNF-alpha inhibitors and the effect of targeting the homologues TL1A-DR3 pathway in chronic inflammatory disorders. AB - A number of anti-tumor necrosis factor alpha (TNF-alpha) biologics have been developed in recent years, such as adalimumab, etanercept, and infliximab for the treatment of chronic inflammatory disorders like rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis and several other novel drugs that target TNF-alpha signaling are still being developed. Indeed, blockade of this pathway seems so important amongst immune-targets that TNF-alpha targeted therapies will continue to have a significant role in the treatment of chronic inflammation. However, up to 40% of RA and IBD patients do not respond to anti TNF-alpha treatment and one possible explanation may be the heterogeneity of chronic inflammatory diseases and a dominance of other significant TNF family members. Indeed, polymorphisms in the TNF family member, TL1A gene, is associated with the development of IBD and increased serum concentrations of TL1A has been demonstrated in patients with various chronic inflammatory disorders. Here, we describe the current knowledge of TL1As immunobiology and present results from human disease, animal models, and pre-clinical intervention studies that point toward development of anti-TL1A therapy as a highly promising strategy for treatment of chronic inflammatory disorders. PMID- 26810854 TI - Policy Campaign: One State's Journey to Influence the Reauthorization of the Children's Health Insurance Program. PMID- 26810855 TI - Mirror, Mirror on the Wall: Children's Preferences and Self-Perceptions of Weight in a Rural Hispanic Community. AB - INTRODUCTION: Although studies have documented parents' misperceptions regarding their children's weight, studies examining preadolescent children's self perceptions of weight-in particular, Hispanic children's self-perceptions of weight-are limited. METHOD: A convenience sample of 424 children from a rural community, aged 8 to 11 years and in grades 3 through 5, participated in this cross-sectional, descriptive, nonexperimental study. Using the Children's Body Image Scale, the children were asked to select a figure representing their actual body perception and a figure representing their ideal body perception. The children were weighed and measured, body mass index (BMI) was calculated, and each child was assigned to one of the Centers for Disease Control and Prevention weight categories: underweight, normal or healthy weight, overweight, or obese. RESULTS: Only BMI category was found to be significantly associated with accurate perception, chi2(3) = 201.4, p < .001, with only 9% of overweight or obese children selecting figures representing their actual BMI category. Actual BMI category, chi2(3) = 8.8, p = .032, and grade level, chi2(2) = 6.7, p = .036, had a significant association with selection of an underweight ideal. Overall, 32% of children selected an underweight figure as ideal. DISCUSSION: Prepubertal children who are either overweight or obese do not accurately perceive their weight status. Rather than focusing solely on weight reduction programs, emphasis should be placed on promoting healthy lifestyles and choices. PMID- 26810857 TI - Do Distinct Exercise Modalities Have Identical Effects on Arterial Stiffness? PMID- 26810856 TI - Aspirin inhibits epithelial-to-mesenchymal transition and migration of oncogenic K-ras-expressing non-small cell lung carcinoma cells by down-regulating E cadherin repressor Slug. AB - BACKGROUND: Cancer metastasis is one of the most common causes of treatment failure and death in cancer patients. It has been acknowledged that aberrant activation of epithelial-to-mesenchymal transition (EMT) program, endows cancer cells with metastatic competence for which E-cadherin switch is a well established hallmark. Suppression of E-cadherin by its transcriptional repressor Slug is thus a determining factor for EMT. Here, we aimed at discerning (i) the molecular mechanisms that regulate Slug/E-cadherin axis in oncogenic K-ras expressing non-small cell lung carcinoma (NSCLC) cells, and (ii) the effect of aspirin in modulating the same. METHODS: The migratory behaviour of NSCLC cell line A549 were deciphered by wound healing assay. Further assessment of the molecular mechanisms was done by western blotting, RT-PCR, confocal microscopy, chromatin immunoprecipitation and small interfering RNA (siRNA)-mediated gene silencing. RESULTS: Here we report that in oncogenic K-ras-expressing A549 cells, Ras/ERK downstream Elk-1 forms p-Elk-1-p300 complex that being directly recruited to SLUG promoter acetylates the same to ensure p65NFkappaB binding for transcriptional up-regulation of Slug, a transcriptional repressor of E-cadherin. Aspirin inhibits EMT and decelerates the migratory potential of A549 cells by down-regulating Slug and thereby up-regulating E-cadherin. Aspirin impedes activation and nuclear translocation of p65NFkappaB, essential for this transcription factor being available for SLUG promoter binding. As a consequence, Slug transcription is down-regulated relieving A549 cells from Slug-mediated repression of E-cadherin transcription, thereby diminishing the metastatic potential of these oncogenic Ras-expressing NSCLC cells. CONCLUSIONS: Cumulatively, these results signify a crucial role of the anti-inflammatory agent aspirin as a novel negative regulator of epithelial-to-mesenchymal transition thereby suggesting its candidature as a promising tool for deterring metastasis of highly invasive K-ras-expressing NSCLC cells. PMID- 26810858 TI - Relation Between Temperature Extremes and Symptom Exacerbation in Patients With Hypertrophic Cardiomyopathy. AB - Warm temperatures induce peripheral vasodilation, decrease afterload, and may concurrently increase the left ventricular outflow tract (LVOT) gradient. We aimed to assess the impact of subjective ambient temperature on hypertrophic cardiomyopathy (HC) symptoms and determine whether they were associated with LVOT gradient, patient quality of life (QOL), and risk of sudden cardiac death (SCD). We identified consecutive patients with HC presenting to a tertiary referral center. Of the 173 patients in the study, 143 (83%) had HC symptoms, with ambient temperature change worsening symptoms for 72 patients (50%). Symptom exacerbation occurred only with heat for 57 (79%), whereas symptoms were exacerbated with cold only or with cold and heat equally for 15 (21%). Patients affected by any temperature exacerbation more commonly were women (p = 0.009), had a lower QOL (p = 0.04), had a family history of HC (p = 0.007), or underwent myectomy (p = 0.01). A greater proportion of patients with heat-only exacerbation had a family history of HC (p = 0.005) and SCD (p = 0.05). The presence of an LVOT gradient either at rest or with provocation was similar in all groups. In conclusion, although no appreciable difference in LVOT gradients were observed between patient groups, approximately half of the patients with HC reporting symptoms at baseline noted worsening of symptoms with temperature changes, with >75% describing heat-induced symptom exacerbation. Furthermore, affected patients more frequently were women, underwent surgical intervention and device implantation, and had an overall lower QOL. PMID- 26810859 TI - Infections, Arrhythmias, and Hospitalizations on Home Intravenous Inotropic Therapy. AB - Inotropes improve symptoms in advanced heart failure (HF) but were associated with higher mortality in clinical trials. Recurrent hospitalizations, arrhythmias, and infections contribute to morbidity and mortality, but the risks of these complications with modern HF therapies are not well known. We collected arrhythmia, infection, and hospitalization data on 197 patients discharged from our institution from January 2007 to March 2013 on intravenous inotropes. Patients were followed until they died, received a transplant or left ventricular assist device, were weaned off inotropes, or remained on inotropes at the end of the study. All patients had stage D HF. At baseline, 30% had a history of ventricular tachycardia, 7.1% had a history of cardiac arrest, and 39% had a history of atrial fibrillation. During follow-up, 33 patients (17%) had one or more implantable cardioverter-defibrillator shocks. Of patients who had shocks, 27 patients (82%) had appropriate shocks for ventricular tachycardia/ventricular fibrillation, 3 patients (9%) had inappropriate shocks, and 3 patients (9%) had both appropriate and inappropriate shocks. The risk of implantable cardioverter defibrillator shock was not related to dose of inotrope (p = 0.605). Fifty-seven patients (29%) had one or more infections during follow-up. Bacteremia was the most common type of infection. Implanted electrophysiology devices did not confer an increased risk of infection. One hundred twelve patients (57%) had one or more hospitalizations during follow-up. Common causes of hospitalizations were worsening HF symptoms (41%), infections (20%), and arrhythmias (12%). In conclusion, arrhythmias, infections, and rehospitalizations are important complications of inotropic therapy. PMID- 26810860 TI - Epidemiology of Out-of-Hospital Cardiac Arrests Among Japanese Centenarians: 2005 to 2013. AB - Although the number of centenarians has been rapidly increasing in industrialized countries, no clinical studies evaluated their characteristics and outcomes from out-of-hospital cardiac arrests (OHCAs). This nationwide, population-based, observation of the whole population of Japan enrolled consecutive OHCA centenarians with resuscitation attempts before emergency medical service arrival from 2005 to 2013. The primary outcome measure was 1-month survival from OHCAs. The multivariate logistic regression model was used to assess factors associated with 1-month survival in this population. Among a total of 4,937 OHCA centenarians before emergency medical service arrival, the numbers of those with OHCAs increased from 70 in 2005 to 136 in 2013 in men and from 227 in 2005 to 587 in 2013 in women. Women accounted for 80.3%. Ventricular fibrillation (VF) as first documented rhythm was 2.5%. The proportions of victims receiving bystander cardiopulmonary resuscitation were 64.2%. The proportion of 1-month survival from OHCAs in centenarians was only 1.1%. In a multivariate analysis, age was not associated with 1-month survival from OHCAs (adjusted odds ratio [OR] for one increment of age 1.01; 95% confidence interval [CI] 0.87 to 1.18). Witness by a bystander (adjusted OR 3.45; 95% CI 1.88 to 6.31) and VF as first documented rhythm (adjusted OR 5.49; 95% CI 2.24 to 13.43) were significant positive predictors for 1-month survival. Cardiac origin was significantly poor in 1-month survival compared with noncardiac origin (adjusted OR 0.37; 95% CI 0.21 to 0.64). In conclusion, survival from OHCAs in centenarians was very poor, but witness by a bystander and VF as first documented rhythm were associated with improved survival. PMID- 26810861 TI - Population pharmacokinetics of oseltamivir and oseltamivir carboxylate in obese and non-obese volunteers. AB - AIMS: The aims of the present study were to compare the pharmacokinetics of oseltamivir and its active antiviral metabolite oseltamivir carboxylate in obese and non-obese individuals and to determine the effect of obesity on the pharmacokinetic properties of oseltamivir and oseltamivir carboxylate. METHODS: The population pharmacokinetic properties of oseltamivir and oseltamivir carboxylate were evaluated in 12 obese [body mass index (BMI) >=30 kg m(-2) ) and 12 non-obese (BMI <30 kg m(-2) ) Thai adult volunteers receiving a standard dose of 75 mg and a double dose of 150 mg in a randomized sequence. Concentration-time data were collected and analysed using nonlinear mixed-effects modelling. RESULTS: The pharmacokinetics of oseltamivir and oseltamivir carboxylate were described simultaneously by first-order absorption, with a one-compartment disposition model for oseltamivir, followed by a metabolism compartment and a one compartment disposition model for oseltamivir carboxylate. Creatinine clearance was a significant predictor of oseltamivir carboxylate clearance {3.84% increase for each 10 ml min(-1) increase in creatinine clearance [95% confidence interval (CI) 0.178%, 8.02%]}. Obese individuals had an approximately 25% (95% CI 24%, 28%) higher oseltamivir clearance, 20% higher oseltamivir volume of distribution (95% CI 19%, 23%) and 10% higher oseltamivir carboxylate clearance (95% CI 9%, 11%) compared with non-obese individuals. However, these altered pharmacokinetic properties were small and did not change the overall exposure to oseltamivir carboxylate. CONCLUSIONS: The results confirmed that a dose adjustment for oseltamivir in obese individuals is not necessary on the basis of its pharmacokinetics. PMID- 26810862 TI - Reduced Dietary Salt for the Prevention of Cardiovascular Disease. PMID- 26810863 TI - The Contribution of Prospective Memory Performance to the Neuropsychological Assessment of Mild Cognitive Impairment. AB - OBJECTIVE: Prospective memory difficulties are a feature of the amnestic form of mild cognitive impairment (aMCI). Although comprehensive test batteries of prospective memory are suitable for clinical practice, they are lengthy, which has detracted from their widespread clinical use. Our aim was to investigate the utility of a brief screening measure of prospective memory, which can be incorporated into a clinical neuropsychological assessment. METHODS: Seventy seven healthy older adults (HOA) and 77 participants with aMCI were administered a neuropsychological test battery, including a prospective memory screening measure (Envelope Task), a retrospective memory measure (CVLT-II), and a multi item subjective memory questionnaire (Prospective and Retrospective Memory Questionnaire; PRMQ) and a single-item subjective memory scale. RESULTS: Compared with HOA participants, participants with aMCI performed poorly on the Envelope Task (eta(2) = .38), which provided good discrimination of the aMCI and HOA groups (AUC = .83). In the aMCI group, there was a small but significant relationship between the Envelope Task and the single-item subjective rating of memory, with the Envelope Task accounting for 5-6% of the variance in subjective memory after accounting for emotional status. This relationship of prospective memory and subjective memory was not significant for the multi-item questionnaire (PRMQ); and, retrospective memory was not a significant predictor of self-rated memory, single-item, or multi-item. CONCLUSION: A brief screening measure of prospective memory, the Envelope Task, provides useful support to traditional memory measures in detecting aMCI. PMID- 26810864 TI - No Evidence of Causal Effects of Blood Pressure on Cognition in the Population at Large. AB - The large body of literature on the association between blood pressure (BP) and cognitive functioning has yielded mixed results, possibly due to the presence of non-linear effects across age, or because BP affects specific brain areas differently, impacting more on some cognitive skills than on others. If a robust association was detected among BP and specific cognitive tasks, the causal nature of reported associations between BP and cognition could be investigated in twin data, which allow a test of alternative explanations, including genetic pleiotropy. The present study first examines the association between BP and cognition in a sample of 1,140 participants with an age range between 10 and 86 years. Linear and quadratic effects of systolic BP (SBP) and diastolic BP (DBP) on cognitive functioning were examined for 17 tests across five functions. Associations were corrected for effects of sex and linear and quadratic effects of age. Second, to test a causal model, data from 123 monozygotic (MZ) twin pairs were analyzed to test whether cognitive functioning of the twins with the higher BP was different from that of the co-twins with lower BP. Associations between BP and cognitive functioning were absent for the majority of the cognitive tests, with the exception of a lower speed of emotion identification and verbal reasoning in subjects with high diastolic BP. In the MZ twin pair analyses, no effects of BP on cognition were found. We conclude that in the population at large, BP level is not associated with cognitive functioning in a clinically meaningful way. PMID- 26810865 TI - Aging Trajectories in Different Body Systems Share Common Environmental Etiology: The Healthy Aging Twin Study (HATS). AB - Little is known about the extent to which aging trajectories of different body systems share common sources of variance. We here present a large twin study investigating the trajectories of change in five systems: cardiovascular, respiratory, skeletal, morphometric, and metabolic. Longitudinal clinical data were collected on 3,508 female twins in the TwinsUK registry (complete pairs:740 monozygotic (MZ), 986 dizygotic (DZ), mean age at entry 48.9 +/- 10.4, range 18 75 years; mean follow-up 10.2 +/- 2.8 years, range 4-17.8 years). Panel data on multiple age-related variables were used to estimate biological ages for each individual at each time point, in linear mixed effects models. A weighted average approach was used to combine variables within predefined body system groups. Aging trajectories for each system in each individual were then constructed using linear modeling. Multivariate structural equation modeling of these aging trajectories showed low genetic effects (heritability), ranging from 2% in metabolic aging to 22% in cardiovascular aging. However, we found a significant effect of shared environmental factors on the variations in aging trajectories in cardiovascular (54%), skeletal (34%), morphometric (53%), and metabolic systems (53%). The remainder was due to environmental factors unique to each individual plus error. Multivariate Cholesky decomposition showed that among aging trajectories for various body systems there were significant and substantial correlations between the unique environmental latent factors as well as shared environmental factors. However, there was no evidence for a single common factor for aging. This study, the first of its kind in aging, suggests that diverse organ systems share non-genetic sources of variance for aging trajectories. Confirmatory studies are needed using population-based twin cohorts and alternative methods of handling missing data. PMID- 26810868 TI - Twinsters the Movie: Reared Apart Twins in Real Time. PMID- 26810867 TI - Cells With Chromosomal Aberrations Trigger Neoplastic Transformations in Humans. AB - Human population cytogenetic studies have revealed that a majority of persons who are prone to developing malignant features possess chromatin bodies termed as marker dots (MDs) measuring nearly 2 to 3 microns. These MDs are seen emanating from certain specific chromosomes, which may be early indicators of neoplastic transformation within cells. PMID- 26810866 TI - Dietary Intake at 9 Years and Subsequent Body Mass Index in Adolescent Boys and Girls: A Study of Monozygotic Twin Pairs. AB - There is a lack of evidence pointing to specific dietary elements related to weight gain and obesity prevention in childhood and adulthood. Dietary intake and obesity are both inherited and culturally transmitted, but most prospective studies on the association between diet and weight status do not take genetics into consideration. The objective of this study was to document the association between dietary intake at 9 years and subsequent Body Mass Index (BMI) in adolescent monozygotic boy and girl twin pairs. This research used data from 152 twin pairs. Dietary data were collected from two 24-hour-recall interviews with a parent and the child aged 9 years. Height and weight were obtained when the twins were aged 9, 12, 13, and 14 years. Intrapair variability analysis was performed to identify dietary elements related to BMI changes in subsequent years. BMI discordant monozygotic twin pairs were also identified to analyze the dietary constituents that may have generated the discordance. After eliminating potential confounding genetic factors, pre-adolescent boys who ate fewer grain products and fruit and consumed more high-fat meat and milk had higher BMIs during adolescence; pre-adolescent girls who consumed more grain products and high-fat meat and milk had higher BMIs during adolescence. Energy intake (EI) at 9 years was not related to BMI in subsequent years. Our study suggests that messages and interventions directed at obesity prevention could take advantage of sex-specific designs and' eventually' genetic information. PMID- 26810871 TI - Reply to letter on our article: Lorente L, Lecuona M, Jimenez A, Raja L, Cabrera J, Gonzalez O, et al. Chlorhexidine-silver sulfadiazine- or rifampicinmiconazole impregnated venous catheters decrease the risk of catheter-related bloodstream infection similarly. Am J Infect Control. 2015 Sep 24. pii:S0196-6553(15)00931-1. doi: 10.1016/j.ajic.2015.08.014. PMID- 26810873 TI - IAEA's ALMERA network: Supporting the quality of environmental radioactivity measurements. AB - The International Atomic Energy Agency coordinates and provides methodological and analytical quality support to the network of Analytical Laboratories for the Measurement of Environmental Radioactivity (ALMERA), comprising 150 laboratories in 84 countries. Annual proficiency tests (PTs) are organized for the network laboratories using sets of different samples typically encountered in environmental and food monitoring laboratories. The PT system is designed to respond to the needs of the network for rapid response and reliable measurement results, and to metrological principles and international standards and guides. Comparison of performance of ALMERA and non-ALMERA laboratories in PTs indicates that the "PT - method development - training - PT" strategy adopted for capability building is beneficial to the network. PMID- 26810874 TI - PREFACE. PMID- 26810876 TI - The Separation And Evaluation Of Personal And Environmental Contributions To Behavior By The Person-Centered Model (PCER). AB - The person-centered environmental representation (PCER) model aims to bring extra personality determiners of behavior measures (stimulus, response form, situation, observer) as known values into the behavioral equations. Illustration begins with the simplest 3-dimensional data box case -- person, test, situation -- in which the response score is a product of the characteristic trait score of the individual and the characteristic interaction of that trait with that kind of performance. In extending this to a particular kind of situation it is recognized that a test-situation interaction term must, realistically, be added. The problem in experiment is to infer the magnitude of the contributors from the 3-sums in the cells of the empirically given data box frame. Three ways of attempting this are described and the third, judged most practical, is illustrated in a plasmode of data typical of experiment. It is shown that the discovery from the frame data of the factor structure, originally put into the contributory test and situation matrices is reasonably good, and it is pointed out that since this can be achieved with only 10 situations, 12 tests and 14 people, the smoothing effect of more typical large samples makes the method practicable. If further research with real data confirms the speculation that the personality factors determining situation reaction are the same as those determining test reaction, a split loading model could be used permitting, as a by-product, assessment of relative variance contributions of differences among persons, stimuli, response forms, and observers. PMID- 26810877 TI - Analysis Of Covariance Structure Tests Of A Criterial Referents Theory Of Attitudes. AB - To test a criterial referents theory of social attitudes, data obtained in the 1960's and 1970's from factor analyses of social attitudes scales administered to students in the U. S. and Europe and to a random sample of Dutch citizens were reanalyzed using an analysis of covariance structure approach. The two-factor model of the basic hypothesis of the theory -- two relatively orthogonal second order factors, liberalism (L) and conservatism (C), underlie social attitudes -- was tested against the one-factor model of the assumption of attitude bipolarity - attitudes have positive and negative poles (L versus C). Although the results of the separate tests of the fit of the two models were mixed, contrast tests of the two models favored the two-factor (dualistic) hypothesis. PMID- 26810875 TI - Physiological Responses and Expression Profile of NADPH Oxidase in Rice (Oryza Sativa) Seedlings under Different Levels of Submergence. AB - BACKGROUND: Flooding due to global climate change is a serious problem that frequently decreases crop yields. Rice fields in flood-prone areas often experience full or partial submergence. Submergence has an adverse effect on internal oxygen availability, sugar status and survival. Complete submergence imposes severe pressure on plants, principally because the excess water in their surroundings deprives them of certain basic resources such as oxygen, carbon dioxide and light for photosynthesis. To better understand the mechanisms involved under different levels of flooding, it is necessary to further observe physiological responses and to identify the Rboh genes involved and determine how they are regulated during submergence. RESULTS: In this study, significant physiological changes were observed in plant height, leaf sheath elongation and chlorophyll a, b and total content under partial and full submergence treatments. Senescence-regulating genes were severely affected under full submergence. Additionally, intracellular oxidative homeostasis was disrupted by overproduction of H2O2 and O2 (-), which affected cell viability and antioxidant enzyme activity, under different levels of submergence. Quantitative RT-PCR analyses revealed that complex regulation of Rboh genes is involved under different levels of submergence. CONCLUSION: Our results demonstrated that the effect of physiological and the transcript levels of OsRboh genes were presented different responses to different levels of submergence in rice seedlings. There have different mechanism in intracellular to response different levels of submergence. Finally we discuss effects of the regulation of OsRboh expression and ROS production which was important to maintain homeostasis to help rice seedlings face different levels of submergence. PMID- 26810878 TI - Physical Attractiveness And Sex As Determinants Of Trait Attributions. AB - Two studies were conducted to examine (a) the implicational qualities of trait terms that describe stereotypic males and females, and (b) the influence of a target person's gender and physical attractiveness on the attributions of traits with specific qualities. On the basis of previous research and theory concerning sex-role and attractiveness stereotypes, it was predicted that the attribution of evaluative traits would be affected by the attractiveness of the target (the what is-beautiful-is-good phenomenon) but not by sex. However, for traits with primarily sex-linked implicational properties, it was expected that the effect of attractiveness would be dependent upon the target's sex such that the attribution of "masculine" traits would vary only with the attractiveness of male targets and the attribution of "feminine" traits only with the attractiveness of female targets. In Study I a multidimensional scaling analysis revealed both evaluative and non-evaluative qualities underlying trait ratings of male and female stereotypes. In Study II the predicted results for evaluative traits were obtained. For "masculine" and "feminine" traits, however, the effects of attractiveness were not symmetrical for male and female targets as originally predicted. The results suggest that attractiveness of males, but not females, leads to a narrowing of the types of traits that are attributed to them. PMID- 26810879 TI - The Growth Of Cluster Analysis: Tryon, Ward, And Johnson. AB - The growth of literature about cluster analysis is studied through an intensive analysis of the work by three men: Johnson, Tryon, and Ward. First, a history of the ideas of these men is discussed. Each of the three represented a different ideological perspective. Next, citation analysis is used to study the impact of the major publication of each man. The citation analysis suggests that there was virtually no overlap among researchers who cite the three authors. Finally, the paper concludes with comments on the cognitive vs. noncognitive factors influencing the growth of cluster analysis as an interest area. PMID- 26810880 TI - Natural Groups And Centroid Clusters Of Mother-Child Dyads Observed In The Home. AB - Cluster analysis (Wishart, 1972) was applied to the interactive behavior of 136 2 1/2-year-old male twins and singletons with their mothers. The clustering was based on the Facilitating Power (FP) that various forms of maternal control exerted on child compliance and non-compliance. The clustering process generated clusters that reflected the pre-existing division of the sample into twins and singletons. In general, singletons seem to be less dependent in their expression of obedience or disobedience on some overt mode of parental verbal control than are twins. Singletons may be actuated more readily by other subtler parental actions, e.g., praise or nonverbal gestures. That the clusters represented "real" distinctions was indicated by a discriminant function analysis which also discriminated between twins and singletons by largely the same measures as the clustering procedure did. The clustering was also validated by a replication via Ward's (1963) method. PMID- 26810881 TI - Detection Of Biological Sex: An Empirical Test Of Cluster Methods. AB - Six cluster methods were subjected to empirical trials evaluating their ability to solve a "dummy" problem, that of detecting an underlying taxonomy of biological sex. Each cluster method was applied to four sets of sex-discriminant self report personality-interest questionnaire items. The validity of each item indicator was empirically determined using biological sex as a criterion variable. The four sets of item-indicators of biological sex were constructed so as to vary in their average item-indicator validity. Three of the cluster methods detected accurately the biological sex taxonomy in most of the trials; the other three methods were seldom accurate. It is argued that for detecting real empirical classes, the cluster methods are of questionable value since we typically lack assurance that the clusters are likely to be accurate and not spurious. It is suggested that use of internal validity or 'consistency' tests could eliminate this shortcoming. PMID- 26810882 TI - A Note On Polynomial Regression. AB - The problem of colinearity among the predictors in the polynomial regression model is discussed. It is shown that when X, the independent variable, follows a standard normal distribution the degree of colinearity in the system rapidly increases as a direct function of the polynomial's degree. Some recommendations of Bradley and Srivastava (1979) are reiterated and some possible alternative approaches are suggested. PMID- 26810883 TI - Toxicokinetics of new psychoactive substances: plasma protein binding, metabolic stability, and human phase I metabolism of the synthetic cannabinoid WIN 55,212-2 studied using in vitro tools and LC-HR-MS/MS. AB - The new psychoactive substance WIN 55,212-2 ((R)-(+)-[2,3-dihydro-5-methyl-3-(4 morpholinylmethyl)pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl]-1-napthalenylmethanone) is a potent synthetic cannabinoid receptor agonist. The metabolism of WIN 55,212 2 in man has never been reported. Therefore, the aim of this study was to identify the human in vitro metabolites of WIN 55,212-2 using pooled human liver microsomes and liquid chromatography-high resolution-tandem mass spectrometry (LC HR-MS/MS) to provide targets for toxicological, doping, and environmental screening procedures. Moreover, a metabolic stability study in pooled human liver microsomes (pHLM) was carried out. In total, 19 metabolites were identified and the following partly overlapping metabolic steps were deduced: degradation of the morpholine ring via hydroxylation, N- and O-dealkylation, and oxidative deamination, hydroxylations on either the naphthalene or morpholine ring or the alkyl spacer with subsequent oxidation, epoxide formation with subsequent hydrolysis, or combinations. In conclusion, WIN 55,212-2 was extensively metabolized in human liver microsomes incubations and the calculated hepatic clearance was comparably high, indicating a fast and nearly complete metabolism in vivo. This is in line with previous findings on other synthetic cannabinoids. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26810884 TI - The shadow of inequitable conduct in the US patent application. AB - Inequitable conduct regarding any single claim can render the entire patent unenforceable and further damage other related patents and applications in the assignee's patent portfolio. The adverse impact of inequitable conduct significantly became a litigation strategy. The US Federal Circuit (CAFC) observed that inequitable conduct as a patent litigation strategy had become a plague and thus tightened the standard for finding inequitable conduct in a case with full court judges. However, under the shadow of previous adverse impact of inequitable conduct, patent applicants may still submit many marginal related references. This study demonstrates that an applicant even prepared an information disclosure statement (IDS) as many as 50 pages. Actually, under the new standard, inequitable conduct would not further produce significant impact in the US patent system. Thus, a patent applicant need not submit marginal references but should distinguish the prior art from the current application, especially for those listed in the IDS, to avoid the novelty rejection. PMID- 26810885 TI - Use of a predictive protocol to measure the antimicrobial resistance risks associated with biocidal product usage. AB - BACKGROUND: In this study we assessed the propensity of biocide exposure in the development of antimicrobial resistance in bacteria. METHODS: Our protocol is based on reporting changes in established antimicrobial susceptibility profiles in biocides and antibiotics after during use exposure to a product. The during use exposure reflects worse conditions of product use during application. It differs from the term low concentration, which usually reflects a concentration below the minimal inhibitory concentration, but not necessarily a concentration that occurs in practice. RESULTS: Our results showed that exposure to triclosan (0.0004%) was associated with a high risk of developing resistance and cross resistance in Staphylococcus aureus and Escherichia coli. This was not observed with exposure to chlorhexidine (0.00005%) or a hydrogen peroxide-based biocidal product (in during use conditions). Interestingly, exposure to a low concentration of hydrogen peroxide (0.001%) carried a risk of emerging resistance to antibiotics if the presence of the oxidizing agent was maintained. We observed a number of unstable clinical resistances to antibiotics after exposure to the cationic biocide and oxidizing agent, notably to tobramycin and ticarcillin clavulanic acid. CONCLUSIONS: Using a decision tree based on the change in antimicrobial susceptibility test results, we were able to provide information on the effect of biocide exposure on the development of bacterial resistance to antimicrobials. Such information should address the call from the U.S. Food and Drug Administration and European Union Biocidal Products Regulation for manufacturers to provide information on antimicrobial resistance and cross resistance in bacteria after the use of their product. PMID- 26810886 TI - Cytomegalovirus infection in a cohort of pregnant women. AB - Enzyme linked immunosorbent assay was used to detect the seroprevalence of cytomegalovirus (CMV) immunoglobulin M (IgM) and immunoglobulin G (IgG) in 300 pregnant women. Seventeen (5.7%) and 274 (91.3%) women were seropositive for IgM and IgG, respectively. There was significant increase in seroprevalence of CMV IgG and no significant increase in seroprevalence of CMV IgM among tested age groups. CMV IgM and IgG seroprevalence differed nonsignificantly by type of residence, the stage of pregnancy, and the level of education. PMID- 26810887 TI - [Yeast urinary tract infections. Multicentre study in 14 hospitals belonging to the Buenos Aires City Mycology Network]. AB - BACKGROUND: Urinary tract infections are a frequent ailment in patients in intensive care units. Candida and other yeasts cause 5-12% of these infections. The value of the finding of any yeast is controversial, and there is no consensus about which parameters are adequate for differentiating urinary infections from colonization or contamination. AIMS: To analyse the epidemiological characteristics of patients with funguria, to determine potential cut-off points in cultures (to distinguish an infection from other conditions), to identify the prevalent yeast species, and to determine the value of a second urine sample. METHODS: A multicentre study was conducted in intensive care units of 14 hospitals in the Buenos Aires City Mycology Network. The first and second samples of urine from every patient were cultured. The presence of white cells and yeasts in direct examination, colony counts, and the identification of the isolated species, were evaluated. RESULTS: Yeasts grew in 12.2% of the samples. There was no statistical correlation between the number of white cells and the fungal colony-forming units. Eighty five percent of the patients had indwelling catheters. Funguria was not prevalent in women or in patients over the age of 65. Candida albicans, followed by Candida tropicalis, were the most frequently isolated yeasts. Candida parapsilosis and Candida glabrata appeared less frequently. The same species were isolated in 70% of second samples, and in 23% of the cases the second culture was negative. CONCLUSIONS: It was not possible to determine a useful cut-off point for colony counts to help in the diagnosis of urinary infections. As in other publications, C. albicans, followed by C. tropicalis, were the most prevalent species. PMID- 26810888 TI - One-pot, highly efficient, asymmetric synthesis of ring-fused piperidine derivatives bearing N,O- or N,N-acetal moieties. AB - We successfully expand the application of lactols or cyclic hemiaminals as nucleophiles for the asymmetric synthesis of both N,O- and N,N-acetal moieties contained in the structure of ring-fused piperidine derivatives. This efficient one-pot protocol involves an organocatalyzed asymmetric aza-Diels-Alder reaction and iminium ion induced cyclization sequence to ultimately deliver heterocyclic compounds with excellent stereoselectivity in high yield, containing three continuous stereogenic centers. PMID- 26810889 TI - [The benefits of prospective cohorts in COPD]. PMID- 26810893 TI - Kinetic, kinematic, magnetic resonance and owner evaluation of dogs before and after the amputation of a hind limb. AB - BACKGROUND: The amputation of a limb is a surgical procedure that is regularly performed in small animal practice. In spite of several clinical reports indicating high owner satisfaction after limb amputation in dogs, an amputation is still very critically seen by the owners, and even by some veterinarians, due to the lack of accurate information about the recovery of amputee patients. Thus, the objective of this study was to prospectively evaluate, both objectively and subjectively, the recovery outcome of dogs undergoing a hind limb amputation. Twelve patients in which a hind limb amputation was scheduled were studied. Kinetic and kinematic gait analyses were performed before the amputation, and 10, 30, 90 and 120 days after surgery. Magnetic resonance (MR) examination of the contralateral stifle joint was performed before and 120 days after amputation. The subjective impressions of the owners were gathered at the same examination times of the gait analyses. RESULTS: Kinetic data showed a redistribution of the load to all remaining limbs after the amputation; ten days after the procedure patients had already established their new locomotory pattern. Kinematic data showed significant differences between sessions in the mean angle progression curves of almost all analyzed joints; however, the ranges of motion were very similar before and after the amputation, and remained constant in the subsequent sessions after the amputation. No changes in the signal intensity of the soft tissues evaluated, and no evidence of cartilage damage or osteoarthritis was seen on the MR examination of the contralateral stifle. Owners evaluated the results of the amputation very positively, both during and at the end of the study. CONCLUSIONS: Dogs had a quick adaptation after a hind limb amputation, and the adaptation process began before the amputation was performed. This happened without evidence of morphologic changes in the contralateral stifle joint, and with a very positive evaluation from the owner. PMID- 26810894 TI - BLAST-based structural annotation of protein residues using Protein Data Bank. AB - BACKGROUND: In the era of next-generation sequencing where thousands of genomes have been already sequenced; size of protein databases is growing with exponential rate. Structural annotation of these proteins is one of the biggest challenges for the computational biologist. Although, it is easy to perform BLAST search against Protein Data Bank (PDB) but it is difficult for a biologist to annotate protein residues from BLAST search. RESULTS: A web-server StarPDB has been developed for structural annotation of a protein based on its similarity with known protein structures. It uses standard BLAST software for performing similarity search of a query protein against protein structures in PDB. This server integrates wide range modules for assigning different types of annotation that includes, Secondary-structure, Accessible surface area, Tight-turns, DNA-RNA and Ligand modules. Secondary structure module allows users to predict regular secondary structure states to each residue in a protein. Accessible surface area predict the exposed or buried residues in a protein. Tight-turns module is designed to predict tight turns like beta-turns in a protein. DNA-RNA module developed for predicting DNA and RNA interacting residues in a protein. Similarly, Ligand module of server allows one to predicted ligands, metal and nucleotides ligand interacting residues in a protein. CONCLUSIONS: In summary, this manuscript presents a web server for comprehensive annotation of a protein based on similarity search. It integrates number of visualization tools that facilitate users to understand structure and function of protein residues. This web server is available freely for scientific community from URL http://crdd.osdd.net/raghava/starpdb . PMID- 26810896 TI - CpG-oligodeoxynucleotides exert remarkable antitumor activity against diffuse malignant peritoneal mesothelioma orthotopic xenografts. AB - BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and locally aggressive disease. DMPM prognosis is dismal, mainly due to the lack of effective treatment options and the development of new therapeutic strategies is urgently needed. In this context, novel immunotherapy approaches can be explored in an attempt to improve DMPM patients' survival. METHODS: We tested the efficacy of CpG-oligodeoxynucleotides (CpG-ODN), synthetic DNA sequences recognized by Toll-like receptor 9 and able to induce innate/adaptive immune response, in two DMPM orthotopic xenografts (MesoII and STO), which properly recapitulate the dissemination pattern of the disease in the peritoneal cavity. Severe combined immunodeficiency mice carrying DMPM xenografts were treated at different stages of tumor development with i.p. delivered CpG-ODN1826 for 4 weeks. CpG-ODN1826 induced modulation in the composition of peritoneal immune infiltrate was assessed by flow cytometry. RESULTS: When administered to early-stage tumors (i.e., 4 days after i.p. DMPM cell injection in mice), the agent exhibited impressive efficacy against MesoII by completely inhibiting tumor take and ascites development (no evidence of tumor masses and ascites in 6/6 mice at necropsy), and also impaired STO tumor take and growth (4/6 tumor-free mice; i.p. tumor masses reduced by 94 % in the 2 remaining mice, P = 0.00005). Interestingly, when tested against late-stage STO tumors (i.e., 11 days after i.p. DMPM cell injection in mice), CpG-ODN1826 was still able to reduce the growth of i.p. tumor masses by 66 % (P = 0.0009). Peritoneal washings of tumor bearing mice revealed a strong increase of macrophage infiltration together with a decrease in the presence of B-1 cells and a reduced IgM concentration after CpG ODN1826 treatment. CONCLUSIONS: Our results indicate that locally administered CpG-ODN1826 is able to markedly affect the growth of both early- and late-stage DMPM orthotopic xenografts in the absence of severe side effects, and suggest a possible clinical role for the agent in the therapy of DMPM. PMID- 26810898 TI - Antisense expression of Gossypium barbadense UGD6 in Arabidopsis thaliana significantly alters cell wall composition. AB - Uridine diphosphate-glucose dehydrogenase (UGD, EC1.1.1.22 oxidizes UDP-Glc (UDP D-glucose) to UDP-GlcA (UDP-D-glucuronate), a critical precursor of cell wall polysaccharides. GbUGD6 from Gossypium barbadense is more highly expressed late in the elongation of cotton fibers (15 d post-anthesis (DPA)) and during the stage of secondary cell wall thickening (30 DPA). Subcellular localization analysis in onion epidermis revealed that fluorescently labeled GbUGD6 protein was distributed throughout the cell membrane, as well as the nucleus and vacuoles. Examination of UGD function in Arabidopsis revealed that the antisense GbUGD6 lines had shorter roots, deferred blossoming, compared to wild-type plants. Activities of associated enzymes were also affected by UGD reduction, and biochemical analysis of cell wall samples showed an increase in cellulose levels and a decrease in UGP-GlcA contents. The results of the present study as well as previous studies on UGD support the conclusion that UGD plays a major role in synthesizing polysaccharides synthesis in the cell wall. PMID- 26810895 TI - Sensitivity of jarrah (Eucalyptus marginata) to phosphate, phosphite, and arsenate pulses as influenced by fungal symbiotic associations. AB - Many plant species adapted to P-impoverished soils, including jarrah (Eucalyptus marginata), develop toxicity symptoms when exposed to high doses of phosphate (Pi) and its analogs such as phosphite (Phi) and arsenate (AsV). The present study was undertaken to investigate the effects of fungal symbionts Scutellospora calospora, Scleroderma sp., and Austroboletus occidentalis on the response of jarrah to highly toxic pulses (1.5 mmol kg(-1) soil) of Pi, Phi, and AsV. S. calospora formed an arbuscular mycorrhizal (AM) symbiosis while both Scleroderma sp. and A. occidentalis established a non-colonizing symbiosis with jarrah plants. All these interactions significantly improved jarrah growth and Pi uptake under P-limiting conditions. The AM fungal colonization naturally declines in AM eucalypt symbioses after 2-3 months; however, in the present study, the high Pi pulse inhibited the decline of AM fungal colonization in jarrah. Four weeks after exposure to the Pi pulse, plants inoculated with S. calospora had significantly lower toxicity symptoms compared to non-mycorrhizal (NM) plants, and all fungal treatments induced tolerance against Phi toxicity in jarrah. However, no tolerance was observed for AsV-treated plants even though all inoculated plants had significantly lower shoot As concentrations than the NM plants. The transcript profile of five jarrah high-affinity phosphate transporter (PHT1 family) genes in roots was not altered in response to any of the fungal species tested. Interestingly, plants exposed to high Pi supplies for 1 day did not have reduced transcript levels for any of the five PHT1 genes in roots, and transcript abundance of four PHT1 genes actually increased. It is therefore suggested that jarrah, and perhaps other P-sensitive perennial species, respond positively to Pi available in the soil solution through increasing rather than decreasing the expression of selected PHT1 genes. Furthermore, Scleroderma sp. can be considered as a fungus with dual functional capacity capable of forming both ectomycorrhizal and non-colonizing associations, where both pathways are always accompanied by evident growth and nutritional benefits. PMID- 26810899 TI - Whey protein concentrate enhances intestinal integrity and influences transforming growth factor-beta1 and mitogen-activated protein kinase signalling pathways in piglets after lipopolysaccharide challenge. AB - Whey protein concentrate (WPC) has been reported to have protective effects on the intestinal barrier. However, the molecular mechanisms involved are not fully elucidated. Transforming growth factor-beta1 (TGF-beta1) is an important component in the WPC, but whether TGF-beta1 plays a role in these processes is not clear. The aim of this study was to investigate the protective effects of WPC on the intestinal epithelial barrier as well as whether TGF-beta1 is involved in these protection processes in a piglet model after lipopolysaccharide (LPS) challenge. In total, eighteen weanling pigs were randomly allocated to one of the following three treatment groups: (1) non-challenged control and control diet; (2) LPS-challenged control and control diet; (3) LPS+5 %WPC diet. After 19 d of feeding with control or 5 %WPC diets, pigs were injected with LPS or saline. At 4 h after injection, pigs were killed to harvest jejunal samples. The results showed that WPC improved (P<0.05) intestinal morphology, as indicated by greater villus height and villus height:crypt depth ratio, and intestinal barrier function, which was reflected by increased transepithelial electrical resistance and decreased mucosal-to-serosal paracellular flux of dextran (4 kDa), compared with the LPS group. Moreover, WPC prevented the LPS-induced decrease (P<0.05) in claudin-1, occludin and zonula occludens-1 expressions in the jejunal mucosae. WPC also attenuated intestinal inflammation, indicated by decreased (P<0.05) mRNA expressions of TNF-alpha, IL-6, IL-8 and IL-1beta. Supplementation with WPC also increased (P<0.05) TGF-beta1 protein, phosphorylated-Smad2 expression and Smad4 and Smad7 mRNA expressions and decreased (P<0.05) the ratios of the phosphorylated to total c-jun N-terminal kinase (JNK) and p38 (phospho-JNK:JNK and p-p38:p38), whereas it increased (P<0.05) the ratio of extracellular signal regulated kinase (ERK) (phospho-ERK:ERK). Collectively, these results suggest that dietary inclusion of WPC attenuates the LPS-induced intestinal injury by improving mucosal barrier function, alleviating intestinal inflammation and influencing TGF-beta1 canonical Smad and mitogen-activated protein kinase signalling pathways. PMID- 26810900 TI - Predicting pre-eclampsia: dealing with both complex models and complex variables. PMID- 26810901 TI - Comparison of statistical models for nested association mapping in rapeseed (Brassica napus L.) through computer simulations. AB - BACKGROUND: Rapeseed (Brassica napus L.) is an important oilseed crop throughout the world, serving as source for edible oil and renewable energy. Development of nested association mapping (NAM) population and methods is of importance for quantitative trait locus (QTL) mapping in rapeseed. The objectives of the research were to compare the power of QTL detection 1- beta(*) (beta(*) is the empirical type II error rate) (i) of two mating designs, double haploid (DH-NAM) and backcross (BC-NAM), (ii) of different statistical models, and (iii) for different genetic situations. RESULTS: The computer simulations were based on the empirical data of a single nucleotide polymorphism (SNP) set of 790 SNPs from 30 sequenced conserved genes of 51 accessions of world-wide diverse B. napus germplasm. The results showed that a joint composite interval mapping (JCIM) model had significantly higher power of QTL detection than a single marker model. The DH-NAM mating design showed a slightly higher power of QTL detection than the BC-NAM mating design. The JCIM model considering QTL effects nested within subpopulations showed higher power of QTL detection than the JCIM model considering QTL effects across subpopulations, when examing a scenario in which there were interaction effects by a few QTLs interacting with a few background markers as well as a scenario in which there were interaction effects by many QTLs (>= 25) each with more than 10 background markers and the proportion of total variance explained by the interactions was higher than 75 %. CONCLUSIONS: The results of our study support the optimal design as well as analysis of NAM populations, especially in rapeseed. PMID- 26810902 TI - Hypoxia enhances the effect of lipopolysaccharide-stimulated IL-1beta expression in human periodontal ligament cells. AB - Oral infection is inflammatory disease caused by bacteria. A major component of gram negative bacteria membrane associated with inflammation is lipopolysaccharide (LPS). Currently, evidence presenting the combined effect of LPS and hypoxia to inflammatory response in human periodontal ligament cells (HPDLs) was yet lacking. Here, we studied whether the influence of oxygen on LPS stimulated inflammatory cytokines in HPDLs. HPDLs were stimulated with LPS in normoxia and hypoxia for 24 h. The mRNA and protein expression of inflammatory cytokines were examined by polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The intracellular mechanisms of these effects were investigated by chemical inhibitors and small interfering RNA (siRNA). The results showed that LPS-stimulated IL-1beta, IL-6, IL-8 in HPDLs in both hypoxia and normoxia. Hypoxia condition enhanced the effect of LPS-stimulated cytokines expression. Apigenin, the hypoxia-inducible factors (HIF)-1alpha inhibitor, totally prevented LPS-stimulated IL-1beta expression in both normoxia and hypoxia. Similar to knockout HIF-1alpha gene expression by siRNA did ?not prevent LPS-stimulated IL-1beta expression. These data concluded that hypoxia increased virulence of LPS-stimulated IL-1beta production in HPDLs. PMID- 26810903 TI - Clinical significance of corrosion of cemented femoral stems in metal-on-metal hips: a retrieval study. AB - PURPOSE: The clinical significance of corrosion of cemented femoral stems is unclear. The purpose of this retrieval study was to: (1) report on corrosion at the stem-cement interface and (2) correlate these findings with clinical data. METHODS: We analysed cemented stems (n = 36) composed of cobalt-chromium (CoCr) and stainless steel (SS) in a series of revised metal-on-metal hips. We performed detailed inspection of each stem to assess the severity of corrosion at the stem cement interface using a scale of 1 (low) to 5 (severe). We assessed the severity of corrosion at each stem trunnion and measured wear rates at the head taper and bearing surfaces. We used non-parametric tests to determine the significance of differences between the CoCr and SS stems in relation to: (1) pre-revision whole blood Co and Cr metal ion levels, (2) trunnion corrosion, (3) bearing surface wear and (4) taper material loss. RESULTS: The corrosion scores of CoCr stems were significantly greater than SS stems (p < 0.01). Virtually all stem trunnions in both alloy groups had minimal evidence of corrosion. The median pre-revision Co levels of implants with CoCr stems were significantly greater than the SS stems (p < 0.01). There was no significant difference in relation to pre-revision Cr levels (p = 0.521). There was no significant difference between the two stem types in relation to bearing wear (p = 0.926) or taper wear (p = 0.148). CONCLUSIONS: Severe corrosion of cemented femoral stems is a common finding at our retrieval centre; surgeons should consider corrosion of CoCr stems as a potential source of metal ions when revising a hip. PMID- 26810904 TI - Intermittent versus continuous sciatic block combined with femoral block for patients undergoing knee arthroplasty. A randomized controlled trial. AB - PURPOSE: Many institutions perform peripheral femoral and/or sciatic nerve blocks for analgesia after total knee arthroplasty. The aim of the present investigation was to compare the analgesic effect of an intermittent sciatic block (boluses on demand only) with a continuous infusion. METHODS: One hundred and forty patients receiving a femoral and a sciatic nerve block (SNB) by catheter were assessed. The femoral catheter was infused continuously in both groups. In the continuous group (n = 70), the sciatic catheter was used continuously as well. In the intermittent group (n = 70), after a single injection of 20 ml ropivacaine 0.75 %, injections into the sciatic catheter were performed on demand only. Frequency of injections, ventral and dorsal numerical pain scores (NRSs) of the knee, functional outcome (degree of flexion/extension) and additional opioid requirements were assessed during the post-operative period. RESULTS: In both groups, dorsal and ventral NRSs were below 3 at rest and below 5 during mobilisation over the complete period of assessment. Differences between the groups could not be observed. The cumulative number of supplemental injections into the sciatic catheter was higher in the intermittent group (52) compared with the continuous group (24; p < 0.05). Groups did not differ from each other with regard to functional outcome and opioid consumption. CONCLUSIONS: The use of a sciatic block performed as intermittent bolus injection on demand only did not affect post-operative outcome parameters with regard to pain scores, functional outcome or opioid requirements. This approach might therefore be considered as an alternative to a continuous infusion concept. ClinicalTrials.gov Identifier: NCT01843153. PMID- 26810905 TI - Modulation of JAK2, STAT3 and Akt1 proteins by granulocyte colony stimulating factor following carbon monoxide poisoning in male rat. AB - Carbon monoxide (CO) is an odorless, colorless, tasteless and non-irritating by product of inefficient combustion of hydrocarbon fuels such as motor vehicle exhausted gases. It is the leading cause of mortality in the USA among all unintentional toxicants. Male rats exposed to CO poisoning in the heart has many cardiovascular effects such as, cardiomyopathy, tachycardia, arrhythmias, and ischemia and in severe cases, myocardial infarction (MI) and cardiac arrest. Cardiomyocyte apoptosis is one of the most frequent consequences in the heart. Granulocyte colony stimulating factor (G-CSF) is a cytokine that mobilizes and differentiates granulocytes from stem cells. It can stimulate many anti-apoptotic pathways such as JAK2-STAT3 and PI3-Akt kinases following cardiac ischemia. G-CSF exerts its anti-apoptotic effects through binding to its specific cell surface receptor. The purpose of this study was to elucidate the mechanism of anti apoptotic effect of G-CSF following CO poisoning. Rats were exposed to CO 1500 or 3000 ppm for 60 min. Animals received G-CSF 100 MUg/kg subcutaneously for five consecutive days after CO intoxication. Western blot analysis was used to evaluate the expression of six proteins namely JAK2, p-JAK2, STAT3, p-STAT3, Akt1 and p-Akt1 following G-CSF 100 MUg/kg consecutive dose administration after CO poisoning. There was a significant difference between phosphorylated proteins including p-JAK2, p-STAT3 and p-Akt1 in the G-CSF groups and those in control groups and there were not any significant differences in total protein among the groups. PMID- 26810906 TI - Prostaglandin associated periorbitopathy. PMID- 26810907 TI - Spectral domain optical coherence tomography in Celestone(r) retinal toxicity. AB - CASE REPORT: After inadvertent intravitreal injection of Celestone(r) (betamethasone sodium phosphate and acetate, benzalkonium chloride) in a patient, the macular spectral domain optical coherence tomography (SD-OCT) images showed hyper-reflectivity, thinning, and irregular spikes in the inner retinal layers. These early findings could explain the toxic secondary anatomical changes due to the drug itself and/or to its excipients. Late and permanent SD-OCT findings included changes in the ellipsoid zone and cystic-like spaces. DISCUSSION: In this case, SD-OCT images can help to better understand the pathophysiology of the retinal damage and to diagnose the associated complications, providing information with prognostic value. PMID- 26810908 TI - Analysis of costs associated with the management and morbidity of diabetic macular oedema and macular oedema secondary to retinal vein occlusion. AB - OBJECTIVE: To analyse the disease burden in patients with diabetic macular oedema (DMO) or with retinal vein occlusion macular oedema (RVOMO) from a societal perspective. METHODS: Observational, cross-sectional, multicentre study conducted on patients >18 years old diagnosed with uni- or bilateral DMO or unilateral RVOMO. Data on the use of health resources from diagnosis was collected, and the impact of disease on work life was assessed. Costs were annualised (euros, January 2014). Differences were contrasted using Chi-squared test (or Fisher Exact test), Mann Whitney-U test or Kruskal-Wallis test (Dunn contrast). RESULTS: A total of 448 patients were included (DMO 255; RVOMO 193). There were significant differences in costs of diagnosis: RVOMO ?1856, bilateral DMO ?1661, and unilateral DMO ?1401 (P<.001) and the aggregate medical costs: RVOMO ?4639, bilateral DMO 6275? and unilateral DMO 6269? (P<.001). Cost by permanent time off work was higher in bilateral DMO ?11712, than in unilateral DMO ?4284?, and than in RVOMO ?1052 (P<.05). Linear regression analysis showed that variables associated with direct health costs were: Diagnosis (bilateral DMO was associated with higher cost), as well as number of days in hospital, number of visits, time of observation, and number of days of time off work. CONCLUSIONS: Patients with bilateral DMO are associated with a higher direct health cost, as well as a higher indirect cost by impact of the disease on work life. PMID- 26810909 TI - Tick iron and heme metabolism - New target for an anti-tick intervention. AB - Ticks are blood-feeding parasites and vectors of serious human and animal diseases. Ixodes ricinus is a common tick in Europe, transmitting tick-borne encephalitis, Lyme borreliosis, anaplasmosis, or babesiosis. Immunization of hosts with recombinant tick proteins has, in theory, the potential to interfere with tick feeding and block transmission of pathogens from the tick to the host. However, the efficacy of tick antigens has, to date, not been fully sufficient to achieve this. We have focused on 11 in silico identified genes encoding proteins potentially involved in tick iron and heme metabolism. Quantitative real-time PCR (qRT-PCR) expression profiling was carried out to preferentially target proteins that are up-regulated during the blood meal. RNA interference (RNAi) was then used to score the relative importance of these genes in tick physiology. Finally, we performed vaccination screens to test the suitability of these proteins as vaccine candidates. These newly identified tick antigens have the potential to improve the available anti-tick vaccines. PMID- 26810910 TI - Evaluation of micro-organism-detaching efficacy from meat samples by spindle or stomacher treatment and quality analysis of suspensions. AB - AIMS: We investigated and compared the efficacy of a new apparatus for detaching micro-organisms from meat samples. METHODS AND RESULTS: The efficacy of Spindle and stomacher in detaching micro-organisms from meat samples was evaluated. Also, evaluation of appropriateness of suspensions generated by both methods for carrying out molecular biological analysis was implemented. A nearly identical correlation and high R(2) were obtained between Spindle and stomacher in Aerobic Plate Count (APC), and no significant differences were observed in detachment of three major foodborne pathogens. The suspension generated by the Spindle showed lower turbidity and total protein concentration. Also, significantly different threshold cycles were observed in Real-time PCR analysis using suspensions generated by both methods. CONCLUSIONS: The Spindle shows nearly identical efficacy with stomacher treatment in detaching micro-organisms from meat samples. Furthermore, the high quality of suspensions generated by the Spindle, in terms of turbidity and total protein assay, allows for a lower threshold cycle than stomached suspension in Real-time PCR. SIGNIFICANCE AND IMPACT OF THE STUDY: The Spindle could be an alternative method for detaching micro-organisms, yielding a higher quality of suspensions which may be better suited for further molecular microbiological analysis. PMID- 26810912 TI - What We Talk About When We Talk About SDM. PMID- 26810913 TI - Cortical thickness changes in patients with Parkinson's disease and impulse control disorders. AB - INTRODUCTION: To investigate gray matter (GM) and cortical thickness (CTh) changes in patients with Parkinson's disease (PD) with and without Impulse Control Disorders (ICDs). METHODS: Fifteen patients with PD with ICDs (ICD+), 15 patients with PD without ICDs (ICD-) and 24 age and sex-matched healthy controls (HCs) were enrolled in the study. Patients were screened for ICDs by the Minnesota Impulsive Disorders Interview (MIDI) and underwent an extensive neuropsychological evaluation. Whole brain structural imaging was performed on a 3T GE MR scanner. Surface-based investigation of CTh was carried out by using Freesurfer Software. We also used voxel-based morphometry to investigate the pattern of GM atrophy. RESULTS: The voxel-wise analysis of the regional differences in CTh revealed that ICD+ patients showed a statistically significant (p<0.01 FDR) thicker cortex when compared to both ICD- patients and HCs in the anterior cingulate (ACC) and orbitofrontal (OFC) cortices. Moreover, cortical thickness abnormalities were positively correlated with ICD severity (p<0.05 FDR). VBM data did not reveal any statistically significant differences in local GM. CONCLUSIONS: Our results demonstrate that ICD+ patients have an increased CTh in limbic regions when compared with ICD- patients at the same disease stage and with an equal daily levodopa equivalent dose. These corticometric changes may play a role in the lack of inhibition of compulsive behaviors. The presence of such structural abnormalities may result from a synergistic effect of dopaminergic therapy in patients with a pre-existing vulnerability to develop an abnormal behavioral response to external stimuli. PMID- 26810914 TI - ACTH-induced dyskinesia in a child with West syndrome (infantile spasms). PMID- 26810915 TI - Neural substrates of excessive daytime sleepiness in early drug naive Parkinson's disease: A resting state functional MRI study. AB - INTRODUCTION: Excessive daytime sleepiness (EDS) is a common non-motor symptom in Parkinson's disease (PD), but its neuropathology remains elusive due to the limited studies and the inclusion of medicated patients. This current study examined the neural substrates of EDS in drug naive PD patients. METHODS: A total of 76 PD patients in the early disease stages were recruited; 16 of them had EDS, while the remaining 60 did not. Resting state functional magnetic resonance imaging (rs-fMRI) was used to determine group differences (patients with EDS vs. patients without EDS) in spontaneous neural activity indicated by regional homogeneity (ReHo). Additionally, functional connectivity (FC) of the regions showing group differences in ReHo with the entire brain was performed. RESULTS: ReHo analysis controlling for gray matter volume, age, gender, general cognition, depression, postural instability gait difficulty, and rapid eye movement sleep behavior disorder showed decreased ReHo in the left cerebellum and inferior frontal gyrus, but increased ReHo in the left paracentral lobule in PD-EDS patients, compared with patients without EDS. FC analysis controlling for the same variables as in the analysis of ReHo revealed that the three regions showing ReHo differences had decreased FC with regions in the frontal, temporal, insular and limbic lobes and cerebellum in PDs with EDS. CONCLUSION: While decreases in ReHo and FC were found, increases in ReHo were also noted, implying both neural downregulation and compensatory mechanisms in early PD patients with EDS. Longitudinal studies are warranted to clarify the long-term impact of EDS in PD. PMID- 26810917 TI - Heteronuclear Ni(ii)-Ln(iii) (Ln = La, Pr, Tb, Dy) complexes: synthesis and single-molecule magnet behaviour. AB - The reaction of hydrated nickel(II) salts (chloride or nitrate) and hydrated lanthanide nitrate salts with the Schiff base ligand 2-methoxy-6-[(E) phenyliminomethyl] phenol (HL) in methanol resulted in the isolation of three isostructural linear heterometallic trinuclear complexes and a heterometallic tetranuclear complex. The molecular structures of these complexes were determined via single crystal X-ray diffraction revealing molecular structures of formulae [Ni2La(L-)6](NO3)0.55(OH)0.45 (1), [Ni2Pr(L-)6](NO3)0.48(OH)0.52 (2), [Ni2Tb(L )6](NO3)0.5(Cl)0.5 (3) and [Ni2Dy2(L-2(o-vanillin)2(CO3)2(NO3)2(MeOH)2] (4). Structural analysis for 1-3 reveals that the lanthanide ion is sandwiched between two Ni(II) ions and the Ni?Ln?Ni metallic core displays a linear arrangement, with an average ?Ni?Ln?Ni bond angle of 179.7 degrees . Analysis of 4 reveals the metal ions are arranged such that two Ni-Dy subunits are bridged by two carbonate ligands via the Dy sites. Direct current magnetic susceptibility measurements for complexes 1-4 reveal that the Ni(II) ions are coupled ferromagnetically with the Tb(III) (3) and Dy(III) (4) ions, and antiferromagnetically with the Pr(III) ion (2). For complex 1 a long range intramolecular ferromagnetic interaction is witnessed between the Ni(II) ions (Ni?Ni = 6.873(9) A) via a closed shell La(III) ion. The magnetic data of 1 were fitted using the HDVV Hamiltonian revealing the following parameters; J = +0.46 cm(-1), g = 2.245, D = +4.91 cm(-1). Alternating current magnetic susceptibility measurements performed on complexes 2-4 revealed that 3 and 4 displayed frequency dependent chi''M signals (Hac = 3.5 Oe and Hdc = 0 Oe) which is a characteristic signature of a single-molecule magnet behaviour. PMID- 26810916 TI - Is there a role for the high-risk multidisciplinary team meeting in thoracic surgery? AB - OBJECTIVES: There is little information on the impact of a high-risk multidisciplinary team (HRMDT) for thoracic surgery. In our unit, patients considered high risk for thoracic surgery have been discussed at this meeting since its inception in June 2013. The aim of this study was to audit our selection of patients discussed at the HRMDT and its effect on patient outcomes. METHODS: Data were prospectively collected on all patients (n = 820) who underwent lung resection for lung cancer between July 2013 and September 2014. Patients were analysed as two groups HRMDT versus non-HRMDT. Referral to the HRMDT was at the operating surgeons' discretion. Referred patients usually had a higher-than-expected mortality or morbidity risk for the indicated procedure. The median time from HRMDT to surgery was 27 days (IQR 27.75). The median follow-up for all patients was 415 days (IQR 240). RESULTS: There were 102 patients in the HRMDT group and 718 in the non-HRMDT group (males 54 vs 46%; P = 0.12). The median duration from HRMDT to surgery was 27 days (IQR 27.75). Mean age (P = 0.0001), cardiac risk score (P = 0.001) and Thoracoscore (P = 0.0001) were significantly higher in the HRMDT group. There was also a significantly higher proportion of pneumonectomies in the HRMDT group (12 vs 4%; P = 0.001). There were no significant differences between the groups in cardiac, cerebrovascular, GI, pulmonary, renal or composite complications. There was no significant difference in 30-day (3 vs 1%; P = 0.24) or 90-day (5 vs 3%; P = 0.48) mortality between the groups. Operated HRMDT patients had better survival at 200 days (P = 0.002), but there was no difference in long-term survival compared with patients turned down for surgery. CONCLUSIONS: Despite a higher predicted mortality rate by Thoracoscore, HRMDT patients had the same outcome as lower risk non-HRMDT patients. Within the HRMDT cohort, survival in the operated patients was significantly better than that in non-operated patients in the short term. The HRMDT has managed to offer patients a radical treatment option who might have been refused surgery prior to this due to their higher risk profile. We would recommend this forum as a means to further assess and discuss high-risk patients. PMID- 26810918 TI - We Are Human Beings. AB - In this paper, I examine Jeff McMahan's arguments for his claim that we are not human organisms, and the arguments of Derek Parfit to the same effect in a recent paper. McMahan uses these arguments to derive conclusions concerning the moral status of embryos and permanent vegetative state (PVS) patients. My claim will be that neither thinker has successfully shown that we are not human beings, and therefore these arguments do not establish the ethical conclusions that McMahan has sought to draw from the arguments in respect of the moral status of embryos and PVS patients. PMID- 26810919 TI - High Power-High Energy Sodium Battery Based on Threefold Interpenetrating Network. AB - A 3D tricontinuous Na3 V2 (PO4 )3 :reduced graphene oxide-carbon nanotube cathode is directly deposited on the current collector without any conductive additives or binders by a facile electrostatic spray deposition (ESD) technique. Such an electrode displays excellent rate capability and long cycling stability, which is rather typical of supercapacitors but is connected here with the much higher energy density of an efficient battery electrode. PMID- 26810921 TI - Ophthalmia neonatorum treatment and prophylaxis: IPOSC global study. AB - INTRODUCTION: Characteristics of ophthalmia neonatorum (ON) amongst paediatric ophthalmologists remain unclear. The purpose of this current study is to examine the incidence, diagnosis, treatment, and prophylaxis of ON cases presenting to members of the American Association of Paediatric Ophthalmology and Strabismus (AAPOS). METHODS: An email containing a web link to a survey was sent to all members of AAPOS. The questionnaire examined the incidence of ON, etiology, diagnostic methods, treatment, and prophylaxis of the disease in different countries around the world. RESULTS: Two hundred and ninety-one ophthalmologists answered the questionnaire. Most were from North America (52.94 %). One hundred and seventy-six (60.69 %) ophthalmologists encountered 0-5 cases of ON per year. The most common pathogens causing ON was Chlamydia trachomatis (35.37 %). Two hundred and forty-two (85.21 %) treat empirically when encountering ON during the first 10 days of life and 205 (75.09 %) after the first 10 days of life. In both cases, erythromycin was the most common first line of treatment. Two hundred and twenty-two (78.72 %) ophthalmologists replied that prophylactic treatment is required in their country. The most common agent for prophylaxis was erythromycin ointment (71.50 %). CONCLUSIONS: We found that the incidence of ON per year per practitioner is 0-5 cases, the most common etiology is C. trachomatis, and most infants receive prophylaxis and treatment. PMID- 26810922 TI - Enhancement of Biogas Yield of Poplar Leaf by High-Solid Codigestion with Swine Manure. AB - The aim of this work was to examine the improvement of anaerobic biodegradability of organic fractions of poplar leaf from codigestion with swine manure (SM), thus biogas yield and energy recovery. When poplar leaf was used as a sole substrate, the cumulative biogas yield was low, about 163 mL (g volatile solid (VS))(-1) after 45 days of digestion with a substrate/inoculum ratio of 2.5 and a total solid (TS) of 22 %. Under the same condition, the cumulative biogas yield of poplar leaf reached 321 mL (g VS)(-1) when SM/poplar leaf ratio was 2:5 (based on VS). The SM/poplar leaf ratio can determine C/N ratio of the cosubstrate and thus has significant influence on biogas yield. When the SM/poplar leaf ratio was 2:5, C/N ratio was calculated to be 27.02, and the biogas yield in 45 days of digestion was the highest. The semi-continuous digestion of poplar leaf was carried out with the organic loading rate of 1.25 and 1.88 g VS day(-1). The average daily biogas yield was 230.2 mL (g VS)(-1) and 208.4 mL (g VS)(-1). The composition analysis revealed that cellulose and hemicellulose contributed to the biogas production. PMID- 26810924 TI - Assessing the Accuracy of Continuous Glucose Monitoring (CGM) Calibrated With Capillary Values Using Capillary or Venous Glucose Levels as a Reference. AB - BACKGROUND: Using the standard venous reference for the evaluation of continuous glucose monitoring (CGM) systems could possibly negatively affect measured CGM accuracy since CGM are generally calibrated with capillary glucose and venous and capillary glucose concentrations differ. We therefore aimed to quantify the effect of using capillary versus venous glucose reference samples on estimated accuracy in capillary calibrated CGM. METHODS: We evaluated 41 individuals with type 1 diabetes mellitus (T1DM) using the Dexcom G4 CGM system over 6 days. Patients calibrated their CGM devices with capillary glucose by means of the HemoCue system. During 2 visits, capillary and venous samples were simultaneously measured by HemoCue and compared to concomitantly obtained CGM readings. The mean absolute relative difference (MARD) was calculated using capillary and venous reference samples. RESULTS: Venous glucose values were 0.83 mmol/L (15.0 mg/dl) lower than capillary values over all glycemic ranges, P < .0001. Below 4 mmol/l (72 mg/dl), the difference was 1.25 mmol/l (22.5 mg/dl), P = .0001, at 4-10 mmol/l (72-180 mg/dl), 0.67 mmol/l (12.0 mg/dl), P < .0001 and above 10 mmol/l (180 mg/dl), 0.95 mmol/l (17.1 mg/dl), P < .0001. MARD was 11.7% using capillary values as reference compared to 13.7% using venous samples, P = .037. Below 4 mmol/l (72 mg/dl) MARD was 16.6% and 31.8%, P = .048, at 4-10 mmol/l (72-180 mg/dl) 12.1% and 12.6%, P = .32, above 10 mmol/l (180 mg/dl) 8.7% and 9.2%, P = .82. CONCLUSION: Using capillary glucose concentrations as reference to evaluate the accuracy of CGM calibrated with capillary samples is associated with a lower MARD than using venous glucose as the reference. Capillary glucose concentrations were significantly higher than venous in all glycemic ranges. PMID- 26810925 TI - Polytetrafluoroethylene Ingestion as a Way to Increase Food Volume and Hence Satiety Without Increasing Calorie Content. AB - Since satiety is largely due to stretch of the stomach and people tend to eat a consistent weight of food, increasing food volume and mass increases satiety. This can be achieved without increasing the calories of food by mixing food with a material that cannot be metabolized. Such a material should be inert, safe, resistant to stomach acid, lack taste, available in powder form, smooth, resistant to heat, and cost effective. Polytetrafluoroethylene (PTFE) is an ideal substance for this purpose. It is a soft plastic that is widely considered to be the most inert material known and is extremely stable. Animal feeding trials showed that rats fed a diet of 25% PTFE for 90 days had no signs of toxicity and that the rats lost weight. This article publishes the data from these subchronic animal feeding trials, reviews the relevant available literature, and hypothesizes that increasing the volume of food by mixing the food with PTFE powder at a ratio of 3 parts food to 1 part PTFE by volume will substantially improve satiety and reduce caloric consumption in people. PMID- 26810926 TI - Single Gold Nanoparticle-Based Colorimetric Detection of Picomolar Mercury Ion with Dark-Field Microscopy. AB - Mercury severely damages the environment and human health, particularly when it accumulates in the food chain. Methods for the colorimetric detection of Hg(2+) have increasingly been developed over the past decade because of the progress in nanotechnology. However, the limits of detection (LODs) of these methods are mostly either comparable to or higher than the allowable maximum level (10 nM) in drinking water set by the US Environmental Protection Agency. In this study, we report a single Au nanoparticle (AuNP)-based colorimetric assay for Hg(2+) detection in solution. AuNPs modified with oligonucleotides were fixed on the slide. The fixed AuNPs bound to free AuNPs in the solution in the presence of Hg(2+) because of oligonucleotide hybridization. This process was accompanied by a color change from green to yellow as observed under an optical microscope. The ratio of changed color spots corresponded with Hg(2+) concentration. The LOD was determined as 1.4 pM, which may help guard against mercury accumulation. The proposed approach was applied to environmental samples with recoveries of 98.3 +/ 7.7% and 110.0 +/- 8.8% for Yuquan River and industrial wastewater, respectively. PMID- 26810927 TI - Ischemic QRS prolongation as a biomarker of severe myocardial ischemia. AB - BACKGROUND: Previous studies have shown that QRS prolongation is a sign of depressed collateral flow and increased rate of myocardial cell death during coronary occlusion. The aims of this study were to evaluate ischemic QRS prolongation as a biomarker of severe ischemia by establishing the relationship between prolongation and collateral flow experimentally in a dog model, and test if the same pattern of ischemic QRS prolongation occurs in man. METHODS: Degree of ischemic QRS prolongation was measured using a novel method in dogs (n=23) and patients (n=52) during coronary occlusion for 5min. Collateral arterial flow was assessed in the dogs. RESULTS: There was a significant correlation between QRS prolongation and collateral flow in dogs (r=0.61, p=0.008). Magnitude and temporal evolution of prolongation during ischemia were similar for dogs and humans (p=0.202 and p=0.911). CONCLUSION: Quantification of ischemic QRS prolongation could potentially be used as a biomarker for severe myocardial ischemia. PMID- 26810930 TI - A Finite-Element Study of Metal Backing and Tibial Resection Depth in a Composite Tibia Following Total Knee Arthroplasty. AB - Prosthetic alignment, patient characteristics, and implant design are all factors in long-term survival of total knee arthroplasty (TKA), yet the level at which each of these factors contribute to implant loosening has not been fully described. Prior clinical and biomechanical studies have indicated tibial overload as a cause of early TKA revision. The purpose of this study was to determine the relationship between tibial component design and bone resection on tibial loading. Finite-element analysis (FEA) was performed after simulated implantation of metal backed (MB) and all-polyethylene (AP) TKA components in 5 and 15 mm of tibial resection into a validated intact tibia model. Proximal tibial strains significantly increased between 13% and 199% when implanted with AP components (p < 0.05). Strain significantly increased between 12% and 209% in the posterior tibial compartment with increased bone resection (p < 0.05). This study indicates elevated strains in AP implanted tibias across the entirety of the proximal tibial cortex, as well as a posterior shift in tibial loading in instances of increased resection depth. These results are consistent with trends observed in prior biomechanical studies and may associate the documented device history of tibial collapse in AP components with increased bone strain and overload beneath the prosthesis. PMID- 26810928 TI - The monoamine oxidase inhibitory activity of essential oils obtained from Eryngium species and their chemical composition. AB - CONTEXT: Monoamine oxidase (MAO) inhibitors are used in the treatment of depression, anxiety disorders, and the symptomatic treatment of Parkinson's disease. Eryngium, the most representative of the Apiaceae family, is well known for the presence of essential oils (EOs), which have already demonstrated MAO inhibitory potential. OBJECTIVE: The objective of this study is to evaluate the MAO inhibitory capacity of the EOs obtained from Eryngium floribundum Cham. & Schlecht. (EF), E. eriophorum Cham. & Schlecht. (EE), E. nudicaule Lam. (EN), E. horridum Malme (EH), and E. pandanifolium Cham. & Schlecht. (EP). MATERIALS AND METHODS: EOs were obtained from fresh whole plants by hydrodistillation (3 h). Chemical analyses were performed by GC/MS using apolar and polar columns, with oven temperature from 60 to 300 degrees C at 3 degrees C/min. The MAO-A and -B activities were evaluated in vitro by an end-point method using kynuramine as the substrate and mitochondrial suspension or human recombinant enzymes as the enzymatic source. DMSO 2%, clorgyline 10(-7) M, and pargyline 10(-6) M were used as controls. RESULTS AND DISCUSSION: EFEO, EEEO, ENEO, EHEO, and EPEO GC/MS analysis showed (E)-caryophyllene (4.9-10.8%), germacrene D (0.6-35.1%), bicyclogermacrene (10.4-17.2), spathulenol (0.4-36.0%), and globulol (1.4-18.6%) as main constituents. None of the EOs inhibited MAO-A activity (4 and 40 MUg/mL). However, EHEO inhibited MAO-B activity with an IC50 value of 5.65 MUg/mL (1-200 MUg/mL). Pentadecane (10 MUM), its major constituent (53.5%), did not display significant MAO-B inhibition. CONCLUSION: The study demonstrates the promising application of Eryngium species as a source of potential central nervous system bioactive secondary metabolites, specially related to neurodegenerative disorders. PMID- 26810935 TI - Hematuria as a Marker of Occult Urinary Tract Cancer: Advice for High-Value Care From the American College of Physicians. AB - BACKGROUND: The presence of blood in the urine, or hematuria, is a common finding in clinical practice and can sometimes be a sign of occult cancer. This article describes the clinical epidemiology of hematuria and the current state of practice and science in this context and provides suggestions for clinicians evaluating patients with hematuria. METHODS: A narrative review of available clinical guidelines and other relevant studies on the evaluation of hematuria was conducted, with particular emphasis on considerations for urologic referral. HIGH VALUE CARE ADVICE 1: Clinicians should include gross hematuria in their routine review of systems and specifically ask all patients with microscopic hematuria about any history of gross hematuria. HIGH-VALUE CARE ADVICE 2: Clinicians should not use screening urinalysis for cancer detection in asymptomatic adults. HIGH VALUE CARE ADVICE 3: Clinicians should confirm heme-positive results of dipstick testing with microscopic urinalysis that demonstrates 3 or more erythrocytes per high-powered field before initiating further evaluation in all asymptomatic adults. HIGH-VALUE CARE ADVICE 4: Clinicians should refer for further urologic evaluation in all adults with gross hematuria, even if self-limited. HIGH-VALUE CARE ADVICE 5: Clinicians should consider urology referral for cystoscopy and imaging in adults with microscopically confirmed hematuria in the absence of some demonstrable benign cause. HIGH-VALUE CARE ADVICE 6: Clinicians should pursue evaluation of hematuria even if the patient is receiving antiplatelet or anticoagulant therapy. HIGH-VALUE CARE ADVICE 7: Clinicians should not obtain urinary cytology or other urine-based molecular markers for bladder cancer detection in the initial evaluation of hematuria. PMID- 26810936 TI - Incremental impact of body mass status with modifiable unhealthy lifestyle behaviors on pharmaceutical expenditure. AB - BACKGROUND: Overweight/obesity is a growing health risk in Korea. The impact of overweight/obesity on pharmaceutical expenditure can be larger if individuals have multiple risk factors and multiple comorbidities. The current study estimated the combined effects of overweight/obesity and other unhealthy behaviors on pharmaceutical expenditure. METHODS: An instrumental variable quantile regression model was estimated using Korea Health Panel Study data. The current study extracted data from 3 waves (2009, 2010, and 2011). RESULTS: The final sample included 7148 person-year observations for adults aged 20 years or older. Overweight/obese individuals had higher pharmaceutical expenditure than their non-obese counterparts only at the upper quantiles of the conditional distribution of pharmaceutical expenditure (by 119% at the 90th quantile and 115% at the 95th). The current study found a stronger association at the upper quantiles among men (152%, 144%, and 150% at the 75th, 90th, and 95th quantiles, respectively) than among women (152%, 150%, and 148% at the 75th, 90th, and 95th quantiles, respectively). The association at the upper quantiles was stronger when combined with moderate to heavy drinking and no regular physical check-up, particularly among males. CONCLUSION: The current study confirms that the association of overweight/obesity with modifiable unhealthy behaviors on pharmaceutical expenditure is larger than with overweight/obesity alone. Assessing the effect of overweight/obesity with lifestyle risk factors can help target groups for public health intervention programs. PMID- 26810934 TI - Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting. AB - OBJECTIVE: Correct inhaler technique is central to effective delivery of asthma therapy. The study aim was to identify factors associated with serious inhaler technique errors and their prevalence among primary care patients with asthma using the Diskus dry powder inhaler (DPI). METHODS: This was a historical, multinational, cross-sectional study (2011-2013) using the iHARP database, an international initiative that includes patient- and healthcare provider-reported questionnaires from eight countries. Patients with asthma were observed for serious inhaler errors by trained healthcare providers as predefined by the iHARP steering committee. Multivariable logistic regression, stepwise reduced, was used to identify clinical characteristics and asthma-related outcomes associated with >=1 serious errors. RESULTS: Of 3681 patients with asthma, 623 (17%) were using a Diskus (mean [SD] age, 51 [14]; 61% women). A total of 341 (55%) patients made >=1 serious errors. The most common errors were the failure to exhale before inhalation, insufficient breath-hold at the end of inhalation, and inhalation that was not forceful from the start. Factors significantly associated with >=1 serious errors included asthma-related hospitalization the previous year (odds ratio [OR] 2.07; 95% confidence interval [CI], 1.26-3.40); obesity (OR 1.75; 1.17 2.63); poor asthma control the previous 4 weeks (OR 1.57; 1.04-2.36); female sex (OR 1.51; 1.08-2.10); and no inhaler technique review during the previous year (OR 1.45; 1.04-2.02). CONCLUSIONS: Patients with evidence of poor asthma control should be targeted for a review of their inhaler technique even when using a device thought to have a low error rate. PMID- 26810937 TI - A Population-Based Cross-Sectional Study of Alcohol Consumption and Risk of Benign Laryngeal Disease in Korean Adults. AB - OBJECTIVE: Studies on alcohol consumption and benign laryngeal disease (BLD) in the general population are rare. The aim of this study was to investigate the relationship between alcohol consumption and BLD in the Korean general population. STUDY DESIGN: This was a cross-sectional study of a national health survey. MATERIALS AND METHODS: Subjects were 3141 noninstitutionalized civilian adults older than 19 years (1313 men and 1828 women) who completed the laryngeal examination of the Korea National Health and Nutrition Examination Survey of 2008. Frequency of drinking was classified into less than once per week, two to three times per week, and more than four times per week. Binge drinking was defined as five or more drinks (>=61 g of alcohol) per episode for men and as four or more drinks (>=41 g of alcohol) per episode for women. Poisson regression analyses were conducted to examine the relationship between alcohol drinking and BLD. RESULTS: Adjusting for covariates (age, sex, income, level of education, occupation, and cigarette smoking), it was found that those who drank more than four times a week, compared with those who drank less than once per week, were more likely to have BLD (risk ratio = 2.15, 95% confidence interval: 1.01-4.59, P < 0.05). However, the amount of alcohol consumed was not associated with BLD. CONCLUSIONS: Frequent drinking (ie, more than four times a week) was found to be a risk factor for BLD. PMID- 26810938 TI - Identification of patients with triple antiphospholipid antibody positivity is platform and method independent. AB - INTRODUCTION: The risk of clinical complications in antiphospholipid syndrome (APS) increases when a patient is positive for all 3 types of antiphospholipid (aPL) antibodies. However, there is a considerable disagreement between various platforms for aCL and anti-beta2-glycoprotein I (anti-beta2GPI) measurement, which leads to discrepancies between these platforms in assessing aPL antibody positivity. OBJECTIVES: The aim of this retrospective cross-sectional study was to assess whether 2 different platforms, the QUANTA Lite enzyme-linked immunosorbent assay and the QUANTA Flash chemiluminescent immunoassay, identify the same subjects as triple positive in a group of patients with APS and comorbid autoimmune diseases. PATIENTS AND METHODS: The study included 220 patients with systemic autoimmune diseases (74 with primary APS; 47 with secondary APS; and 99 with systemic lupus erythematosus without APS). All patients were tested for IgG and IgM aCL and anti-beta2GPI antibodies using both platforms. RESULTS: The agreement between the positive results for individual antibodies obtained using both platforms was not full, ranging from 81.8% to 90.9% in a pair-wise comparison. However, the number of patients with triple aPL antibody positivity was similar (80 by QUANTA Lite and 86 by QUANTA Flash); the agreement between the 2 platforms for the identification of patients with triple antibody positivity was 95.5% (Cohen's kappa coefficient = 0.90). This resulted in a similar risk for APS-related clinical complications: an odds ratio of 24.9 for QUANTA Lite and of 24.7 for QUANTA Flash. CONCLUSIONS: Our results confirm a strong association between triple aPL antibody positivity and APS and indicate that the identification of patients with triple antibody positivity is platform independent. When aPL antibody profiles are assessed, the agreement between various methods is much higher than that for individual antibodies. PMID- 26810940 TI - Pediatric intestinal obstruction in Malawi: characteristics and outcomes. AB - BACKGROUND: Intestinal obstruction (IO) is a common pediatric surgical emergency in sub-Saharan Africa with high morbidity and mortality, but little is known about its etiopathogenesis in Malawi. METHODS: Retrospective analysis of patients seen from February 2012 to June 2014 at Kamuzu Central Hospital in Lilongwe, Malawi (n = 3,407). Pediatric patients with IO were analyzed (n = 130). RESULTS: Overall, 57% of patients were male with a mean age of 3.5 +/- 4.1 years. A total of 52% of patients underwent operative intervention. The overall mortality rate was 3%. Leading causes of IO were Hirschprung's 29%, anorectal malformation 18%, and intussusception 4%. Neonates and patients with congenital causes of IO underwent surgery less frequently than infants and/or children and patients with acquired causes, respectively. These groups also demonstrated increased number of days from admission to surgery. CONCLUSIONS: Increasing pediatric-specific surgical education and/or training and expanding access to resources may improve mortality after IO in poor medical communities within sub-Saharan Africa. PMID- 26810939 TI - Outcomes after resection of cortisol-secreting adrenocortical carcinoma. AB - BACKGROUND: We sought to define the impact of cortisol-secreting status on outcomes after surgical resection of adrenocortical carcinoma (ACC). METHODS: The U.S ACC group database was queried to identify patients who underwent ACC resection between 1993 and 2014. The short-term and long-term outcomes were assessed. RESULTS: The incidence of all functional and cortisol-secreting tumors was 40.6% and 22.6%, respectively. On multivariable analysis, cortisol secretion remained associated with an increased risk of postoperative complications (odds ratio = 2.25, 95 % confidence interval = 1.04 to 4.88; P = .04). At a median follow-up of 17.6 months, 118 patients (50.4%) had developed a recurrence. On multivariable analysis, after adjusting for patient and disease-related factors cortisol secretion independently predicted shorter recurrence-free survival (Hazard ratio = 2.05, 95% confidence interval = 1.16 to 3.60; P = .01). CONCLUSIONS: Cortisol secretion was associated with an increased risk of postoperative morbidity. Recurrence remains high among patients with ACC after surgery; cortisol secretion was independently associated with a shorter recurrence-free survival. Tailoring postoperative surveillance of ACC patients based on their cortisol secreting status may be important. PMID- 26810942 TI - Repeatability of echocardiographic parameters to evaluate the hemodynamic relevance of patent ductus arteriosus in preterm infants: a prospective observational study. AB - BACKGROUND: The hemodynamically relevant patent ductus arteriosus in preterm infants is not well defined. Different clinical and echocardiographic parameters are used and the diagnostic accuracy is unknown because of the lack of a gold standard definition. Our study evaluates the inter-observer repeatability of echocardiographic and Doppler-ultrasound parameters. METHODS: This prospective observational study included 19 very low birth weight preterm infants (median [interquartile range]: gestational age 28.0 (28.0-29.0) weeks, birth weight 1130 (905-1321) g, postnatal age at measurement 8.7 (4.8-23.5) d) with a clinical suspicion of ductal patency in whom 27 repeated echocardiographic and Doppler ultrasound examinations were performed within 30 min by 2 of 3 independent observers (54 measurements overall). The repeatability index (=2 times the standard deviation of the differences/mean of all measurements) according to Bland and Altman was used to assess repeatability of different parameters. RESULTS: The repeatability indices of the echocardiographic parameters (left Atrium-to-Aortic root-ratio, diameter of the patent ductus arteriosus at its narrowest part, the left-ventricular-preejection-period-to-ejection-time-ratio and the ratio of the velocity time integrals in the large vessels were 16, 21, 23 and 26 % respectively. The repeatability indices of Doppler-ultrasound measurements (resistance index in celiac artery and anterior cerebral artery) were 11 and 14 %, respectively. CONCLUSIONS: The inter-observer repeatability of all echocardiographic parameters was poor compared to that of resistance indices in peripheral vessels. Therefore, interventions for ductal patency should be indicated based on averaged repeated rather than single measurements, especially when measured values are close to their cut-off value - both in clinical routine and for study purposes. PMID- 26810943 TI - A cross-sectional investigation of acceptance of health information technology: A nationwide survey of community pharmacists in Turkey. AB - BACKGROUND: Health information technologies have become vital to health care services. In that regard, successful use of information technologies in pharmaceutical services is important to manage, control and maintain pharmaceutical transactions, which increase the quality of health care delivery. OBJECTIVE: This study aimed to identify influencing factors on pharmacists' acceptance of pharmaceutical service systems. METHODS: A cross-sectional study was conducted employing a research model based on technology acceptance theories. A parsimonious model was developed, and a self-reported questionnaire was distributed online. Community pharmacists participated voluntarily via the website of Turkish Pharmacists' Association. The data was analyzed employing Structural Equation Modeling. RESULTS: From 77 out of 81 cities of Turkey, 2169 community pharmacists participated to the survey with 43% response rate. Perceived usefulness, perceived ease of use, system factors and perceived behavioral control explained 47% of total variance in pharmacists' intention to use the pharmaceutical technology. CONCLUSION: The findings of the research provided insight about relations of influencing factors and practical implications regarding perceived behaviors and system use. Future researchers would benefit from the study design and findings. The study is also valuable for being the first nationwide study conducted on pharmacists about user attitudes toward a technology. PMID- 26810944 TI - Comment on "binge drinking and alcohol prices". PMID- 26810941 TI - New perspectives on mTOR inhibitors (rapamycin, rapalogs and TORKinibs) in transplantation. AB - The macrolide rapamycin and its analogues (rapalogs) constitute the first generation of mammalian target of rapamycin (mTOR) inhibitors. Since the introduction of rapamycin as an immunosuppressant, there has been extensive progress in understanding its complex mechanisms of action. New insights into the function of mTOR in different immune cell types, vascular endothelial cells and neoplastic cells have opened new opportunities and challenges regarding mTOR as a pharmacological target. Currently, the two known mTOR complexes, mTOR complex (mTORC) 1 and mTORC2, are the subject of intense investigation, and the introduction of second-generation dual mTORC kinase inhibitors (TORKinibs) and gene knockout mice is helping to uncover the distinct roles of these complexes in different cell types. While the pharmacological profiling of rapalogs is advanced, much less is known about the properties of TORKinibs. A potential benefit of mTOR inhibition in transplantation is improved protection against transplant-associated viral infections compared with standard calcineurin inhibitor-based immunosuppression. Preclinical and clinical data also underscore the potentially favourable antitumour effects of mTOR inhibitors in regard to transplant-associated malignancies and as a novel treatment option for various other cancers. Many aspects of the mechanisms of action of mTOR inhibitors and their clinical implications remain unknown. In this brief review we discuss new findings and perspectives of mTOR inhibitors in transplantation. PMID- 26810945 TI - Effect of the Hydrogen Bond in Photoinduced Water Dissociation: A Double-Edged Sword. AB - Photoinduced water dissociation on rutile-TiO2 was investigated using various methods. Experimental results reveal that the water dissociation occurs via transferring an H atom to a bridge bonded oxygen site and ejecting an OH radical to the gas phase during irradiation. The reaction is strongly suppressed as the water coverage increases. Further scanning tunneling microscopy study demonstrates that hydrogen bonds between water molecules have a dramatic effect on the reaction. Interestingly, a single hydrogen bond in water dimer enhances the water dissociation reaction, while one-dimensional hydrogen bonds in water chains inhibit the reaction. Density functional theory calculations indicate that the effect of hydrogen bonds on the OH dissociation energy is likely the origin of this remarkable behavior. The results suggest that avoiding a strong hydrogen bond network between water molecules is crucial for water splitting. PMID- 26810946 TI - Dimensions Of Social Stratification For Whites And Blacks. AB - The aim of this study was to determine the major dimensions of social stratification for whites as well as blacks. A survey was conducted with household heads in the Toledo, Ohio area of both races, using an interview that covered a comprehensive set of potentially important variables. Eighteen first order factors were found for whites and 19 for blacks. Five factors matched in the two samples: social status, residence, organization activity, political activity and efficacy, and main support's social status. Other important factors, unique to each sample, were: for whites, self-employed and majority group membership, and for blacks, class consciousness and method variance. Second- and third-order factors were also obtained, but they were difficult to interpret. The findings indicate that stratification is more complex than anticipated by current conceptualizations and previous research. PMID- 26810947 TI - The Development Of Attribution Theory Into Spectrad Theory, Using The General Perceptual Model. AB - Attribution theory is in need of a multivariate model to handle its problems. A model for handling the causes of perceptual difference (misperception) in estimating traits in people already exists in trait view theory. A natural extension of this model will cover the remaining half of attribution research: that concerned with perception of the causal action of situations. The model, integrating both, is a subsumption of the psychology of perception under the general behavioral equation. Spectrad theory is so named because it combines a tetrad of spectra (vectors) for (1) the contextual action of (a) the traits, and (b) the situation of the perceived person or situation and (2) the construing action of (a) the traits and (b) the situation of the perceiver. All four enter into predicting the deviation of a perception from the true value (operationally defined) of (a) a trait score, and (b) the behavioral indices by which the meaning and causal action of a situation are expressed. PMID- 26810948 TI - The Behavior Of Number-Of-Factors Rules With Simulated Data. AB - issues related to the decision of the number of factors to retain in factor analysis are identified, and three widely-used decision rules -- the Kaiser Guttman, scree, and likelihood ratio tests -- are isolated for empirical study. Using two differing structural models and incorporating a number of relevant independent variables (such as number of variables, ratio of number of factors to number of variables, variable communality levels, and factorial complexity), the authors simulated 144 population data sets and, then, from these, 288 sample data sets, each with a precisely known (or incorporated) number of factors. The Kaiser Guttman and scree rules were applied to the population data in Part I of the study, and all three rules were applied to the sample data sets in Part II. Overall trends and interactive results, in terms of the independent variables examined, are discussed in detail, and methods are presented for assessing the quality of the number-of-factors indicated by a particular rule. PMID- 26810949 TI - The Structure Of Activation And Emotion. AB - Three experiments are reported which examine the structure of experienced activation and emotion. Initially the interest was in activation. A factor analysis of a study of self report ratings of experienced emotion and a multi dimensional scaling analysis of a study of judged similarities in the experiences associated with words descriptive of activation states revealed that activation would appear to be best conceptualized as a four category structure simi1ar to that proposed by Thayer (1967). A multidimensional scaling analysis of a set of judgments regarding the similarities of experiences associated with words descriptive of both activation and emotion located the activation and emotion words in a four dimensional Euclidian space where a dimensional rather than a categorical structure appeared to be the more appropriate interpretation. The implications of these findings for existing theories of emotion and activation are discussed with particular reference to the theories of emotion put forward by Schachter and Singer (1962) and Mandler (1975). PMID- 26810950 TI - Factors Influencing Four Rules For Determining The Number Of Components To Retain. AB - The performance of four rules for determining the number of components to retain (Kaiser's eigenvalue greater than unity, Cattell's SCREE, Bartlett's test, and Velicer's MAP) was investigated across four systematically varied factors (sample size, number of variables, number of components, and component saturation). Ten sample correlation matrices were generated from each of 48 known population correlation matrices representing the combinations of conditions. The performance of the SCREE and MAP rules was generally the best across all situations. Bartlett's test was generally adequate except when the number of variables was close to the sample size. Kaiser's rule tended to severely overestimate the number of components. PMID- 26810951 TI - Correlation Coefficients For More Than One Scale Type. AB - The problem of correlating variables from different scale types is discussed. A general correlation coefficient, based on symmetrization theory, is derived. This coefficient is invariant over permitted transformations of the variables for their respective (possibly nonequivalent) scale types. Such a general coefficient is called an E-correlation family. One such family (based on the product-moment correlation coefficient and a nominal scale correlation coefficient), is given for the set composed of interval, ordinal and nominal scales. Finally the individual comparison problem over variables on different scale types is discussed and a solution is proposed. PMID- 26810953 TI - [Health education in transplant patients and their families in an intensive care unit]. AB - Health Education (HE) is extremely important in transplant patients and their families in order to promote suitable self-care in this new stage of life. Intensive Care Units offer various opportunities by nurses in order to improve their Health Education. This process could start in this unit where the interaction between nurse and family is constant. The HE of transplant patient includes three dimensions: Knowledge: information about self-care in order to have a healthy way of life, and getting some information on how to reduce anxiety in patients and their families; Skills: as regards the abilities to properly apply the Health Education, where the families are really important; and finally Attitudes: ambivalent attitudes that are experienced by transplant patients. The objective is to describe the level of development of HE for critical transplant patients and their families from Intensive Care Units. A non-systematic literature review was performed in Pubmed and CINHAL data bases. In conclusion, it is emphasised that the skill of the HE nurse in an Intensive Care Units is important to promote lifestyles appropriate to the cognitive, affective, and psychomotor needs of transplant patients. Its implementation entails positive effects on clinical outcomes of the patient, decreased morbidity and mortality, costs, and health resources. PMID- 26810954 TI - The politics of insight. AB - Previous studies showed that liberals and conservatives differ in cognitive style. Liberals are more flexible, and tolerant of complexity and novelty, whereas conservatives are more rigid, are more resistant to change, and prefer clear answers. We administered a set of compound remote associate problems, a task extensively used to differentiate problem-solving styles (via insight or analysis). Using this task, several researches have proven that self-reports, which differentiate between insight and analytic problem-solving, are reliable and are associated with two different neural circuits. In our research we found that participants self-identifying with distinct political orientations demonstrated differences in problem-solving strategy. Liberals solved significantly more problems via insight instead of in a step-by-step analytic fashion. Our findings extend previous observations that self-identified political orientations reflect differences in cognitive styles. More specifically, we show that type of political orientation is associated with problem-solving strategy. The data converge with previous neurobehavioural and cognitive studies indicating a link between cognitive style and the psychological mechanisms that mediate political beliefs. PMID- 26810955 TI - Osteoneogenesis due to periosteal elevation with degradable and nondegradable devices in Gottingen Minipigs. AB - INTRODUCTION: Periosteal distraction or elevation has been known as an experimental method to induce new bone formation. Although it uses the principles of distraction osteogenesis no further osteotomy is necessary. The purpose of this study was to test devices of different materials and to evaluate the point of origin of the new bone formation. MATERIAL & METHODS: On each calvaria of twelve male adult Gottingen Minipigs three devices were implanted. The materials used were degradable PDLLA (poly-DL-lactide), PGA (polyglycolic acid) and nondegradable Ti (titanium). After a consolidation time of 2, 4 and 6 weeks days a total of 36 specimens were harvested. To identify the total amount of newly created bone, micro-CT and histological analysis were performed. RESULTS: All degradable devices collapsed to a certain extent within the observation time but osteoneogenesis took place in all materials after a consolidation time of 2, 4 and 6 weeks after implantation above and under the devices. No statistical significant differences between the materials were found. However, most bone formation took place in the space under the periosteum and above the devices (p < 0.001). CONCLUSION: Periosteal elevation can produce new bone formation with degradable devices, which derives from the periosteum and the underlying bone. In this interaction the periosteum seems to contain the larger share. PMID- 26810956 TI - Synthesis of hydrazinoheterocycles from Morita-Baylis-Hillman adducts of nitroalkenes with azodicarboxylates. AB - Conjugated nitroalkenes and nitrodienes undergo smooth alpha-hydrazination with azodicarboxylates through an imidazole catalyzed carbon-heteroatom bond formation under Morita-Baylis-Hillman conditions. The resulting hydrazinonitroalkenes take part in 1,3-dipolar cycloaddition with azide under mild conditions to give hydrazinotriazoles. A [3 + 2] annulation with phenols and naphthols involving Michael addition and cyclization as the key steps lead to arenodihydrofurans bearing a key hydrazinodicarboxylate moiety. Both regioisomers of naphthodihydrofurans could be synthesized by our methodology by employing the appropriate naphthol. PMID- 26810957 TI - Test purchase, synthesis and characterization of 3-fluorophenmetrazine (3-FPM) and differentiation from its ortho- and para-substituted isomers. AB - The knowledge captured in patent and scientific research literature stimulates new ideas and fosters new drug development efforts. Manufacturers and entrepreneurs dedicated to the sale of 'research chemicals' and/or new psychoactive substances (NPS) also make use of access to information to identify, prepare, and launch a range of new substances. One of the most recent compounds to appear on the NPS market is the phenmetrazine analog 3-fluorophenmetrazine (3 FPM) which represents one of many phenylmorpholines designed to explore treatment options in areas such as obesity and drug dependence. The anorectic drug analogs phenmetrazine and phendimetrazine, used as prescription medicines before they were withdrawn, feature amphetamine-like properties associated with monoamine release. Available data on 3-FPM suggest that the effects might show mechanistic overlaps. This study describes the synthesis and extensive analytical characterization of 3-FPM and its differentiation from synthesized ortho- and para- substituted isomers, 2-FPM and 4-FPM, respectively. This study was triggered by the purchase of five powdered samples advertised as 3-FPM by five different Internet vendors based in the United Kingdom. The analytical data obtained for the vendor samples were consistent with the synthesized 3-FPM standard and differentiation between all three isomers was possible. The presence of positional isomers and the absence of suitable reference material can cause difficulties in the day-to-day operation of forensic work and given the rate at which many of the newly emerging NPS appear on the market, a comprehensive approach is needed when attempting to decipher the identity of NPS arriving onto the drug market. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26810960 TI - Eye pathology in the works of Vincent van Gogh. PMID- 26810958 TI - Healthcare needs of displaced women: Osire refugee camp, Namibia. AB - AIM: The aim of this study was to explore and describe the experiences of healthcare needs of displaced women in the Osire refugee camp in Namibia. BACKGROUND: Namibia is a country where displaced people from other African countries seek refuge as a result of their own country's political instability. All displaced people are hosted in the Osire camp, which is a highly protected area. There are more women than men in the camp and their health is often compromised. METHODS: In this descriptive phenomenological study, the natural dimension of the experiences of the participants of their healthcare needs were explored through in-depth interviews and reflected upon through transcendental processes to formulate the phenomenological dimension thereof. FINDINGS: The essence of displaced women's healthcare needs was "the need for the restoration of hope and human dignity". Their needs refer to measures to enhance their autonomy and freedom; skills training; certainty about their future; security with aid distribution; protection against stigmatization due to human immunodeficiency virus (HIV) infection; protection against abuse; and participation in reproductive health care. DISCUSSION: When displaced women are admitted in a camp they lose their freedom to make decisions about everyday functioning and future. They thus develop feelings of insecurity and vulnerability. CONCLUSION: The participants referred to several factors that were detrimental for their well-being. The essence of their needs was "the need for the restoration of hope and human dignity" that could only be achieved when their needs are addressed. IMPLICATIONS FOR NURSING: As nurses are in close contact with displaced women in refugee camps they should negotiate opportunities for the women to discuss their concerns with the camp officials. IMPLICATIONS FOR HEALTH AND SOCIAL DEVELOPMENT POLICY: Policies should make provision for the involvement of displaced people in all aspects that relate to their everyday and future living arrangements. PMID- 26810961 TI - Neurotrophic keratitis after transscleral diode laser cyclophotocoagulation. AB - OBJECTIVE: To study the relationship between treatment with diode laser transscleral cyclophotocoagulation and development a neurotrophic keratitis due to the damage of the sensitive corneal innervation. METHODS: A study was conducted on 5 eyes of 5 patients who were treated with diode laser transscleral cyclophotocoagulation and soon developed neurotrophic ulcers. Personal characteristics of the patients were collected, as well as refraction and risk factors for corneal hypoesthesia, and the parameters of the laser used in the surgery. RESULTS: It was found that the 5 patients had predisposing factors of corneal hypoesthesia prior to surgery (chronic use of topical beta blockers, surgery with corneal incisions, diabetes mellitus, or corneal dystrophies); however none had developed neurotrophic keratitis until the cyclophotocoagulation was performed. It also showed that 4 of them were highly myopic, and they all were treated with high laser parameters (with an average of 2880 mW for 3s at an average surface of 275 degrees ), triggering neurotrophic ulcers between 10 and 35 days after surgery. CONCLUSION: Neurotrophic keratitis is a rare complication that can occur after diode laser transscleral cyclophotocoagulation, secondary to the damage of the long ciliary nerves. The emergence of this disorder can be triggered by the existence of previous risk factors, including high myopia, thus it is important to respect the recommended treatment parameters to prevent the development of this disorder. PMID- 26810962 TI - An ophthalmologist Pope. PMID- 26810963 TI - Dietary fiber intake and depressive symptoms in Japanese employees: The Furukawa Nutrition and Health Study. AB - OBJECTIVE: Dietary fiber may play a favorable role in mood through gut microbiota, but epidemiologic evidence linking mood to dietary fiber intake is scarce in free-living populations. We investigated cross-sectionally the associations of dietary intakes of total, soluble, insoluble, and sources of fiber with depressive symptoms among Japanese workers. METHODS: Participants were 1977 employees ages 19-69 y. Dietary intake was assessed via a validated, brief self-administered diet history questionnaire. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Logistic regression was used to estimate odds ratios of depressive symptoms adjusted for a range of dietary and non-dietary potential confounders. RESULTS: Dietary fiber intake from vegetables and fruits was significantly inversely associated with depressive symptoms. The multivariable-adjusted odds ratios (95% confidence intervals) for the lowest through the highest tertile of vegetable and fruit fiber were 1.00 (reference), 0.80 (0.60-1.05), and 0.65 (0.45-0.95), respectively (P for trend = 0.03). Dietary intake of total, soluble, insoluble, and cereal fiber was not associated with depressive symptoms. CONCLUSIONS: Higher dietary fiber intake from vegetables and fruits may be associated with lower likelihood of having depressive symptoms. PMID- 26810970 TI - Relationship of Grafted FGF-2-Overexpressing Neural Stem/Progenitor Cells With the Vasculature in the Cerebral Cortex. AB - Neural progenitor cells (NPCs) overexpressing fibroblast growth factor 2 (FGF-2) have the distinct tendency to associate with the vasculature and establish multiple proliferative clusters in the perivascular environment after transplantation into the cerebral cortex. Strikingly, the vascular clusters of progenitor cells give rise to immature neurons after ischemic injury, raising prospects for the formation of ectopic neurogenic niches for repair. We investigated the spatial relationship of perivascular clusters with the host vascular structures. FGF-2-GFP-transduced NPCs were transplanted into the intact somatosensory rat cortex. Confocal microscopic analysis revealed that grafted cells preferentially contacted venules at sites with aquaporin-4-positive astrocytic endfeet and avoided contacts with desmin-positive pericytes. Electron microscopic analysis confirmed that grafted cells preferentially made contact with astroglial endfeet, and only a minority of them reached the endothelial basal lamina. These results provide new insights into the fine structural and anatomical relationship between grafted FGF-2-transduced NPCs and the host vasculature. PMID- 26810964 TI - A review of clinical models for the evaluation of human TB vaccines. AB - While much progress has been made in the fight against the scourge of tuberculosis (TB), we are still some way from reaching the ambitious targets of eliminating it as a global public health problem by the mid twenty-first century. A new and effective vaccine that protects against pulmonary TB disease will be an essential element of any control strategy. Over a dozen vaccines are currently in development, but recent efficacy trial data from one of the most advanced candidates have been disappointing. Limitations of current preclinical animal models exist, together with a lack of a complete understanding of host immunity to TB or robust correlates of disease risk and protection. Therefore, in the context of such obstacles, we discuss the lessons identified from recent efficacy trials, current concepts of biomarkers and correlates of protection, the potential of innovative clinical models such as human challenge and conducting trials in high-incidence settings to evaluate TB vaccines in humans, and the use of systems vaccinology and novel technologies including transcriptomics and metabolomics, that may facilitate their utility. PMID- 26810972 TI - 24-h urinary sodium excretion is associated with obesity in a cross-sectional sample of Australian schoolchildren. AB - Emerging evidence indicates that dietary Na may be linked to obesity; however it is unclear whether this relationship is independent of energy intake (EI). The aim of this study was to assess the association between Na intake and measures of adiposity, including BMI z score, weight category and waist:height ratio (WHtR), in a sample of Australian schoolchildren. This was a cross-sectional study of schoolchildren aged 4-12 years. Na intake was assessed via one 24-h urine collection. BMI was converted to age- and sex-specific z scores, and WHtR was used to define abdominal obesity. In children aged >=8 years, EI was determined via one 24-h dietary recall. Of the 666 children with valid urine samples 55 % were male (average age 9.3 (sd 1.8) years). In adjusted models an additional 17 mmol/d of Na was associated with a 0.10 higher BMI z score (95 % CI 0.07, 0.13), a 23 % (OR 1.23; 95 % CI 1.16, 1.31) greater risk of being overweight/obese and a 15 % (OR 1.15; 95 % CI 1.09, 1.23) greater risk of being centrally obese. In the subsample of 8-12-year-old children (n 458), adjustment for EI did not markedly alter the associations between Na and adiposity outcomes. Using a robust measure of daily Na intake we found a positive association between Na intake and obesity risk in Australian schoolchildren, which could not be explained by total energy consumption. To determine whether this is a causal relationship, longitudinal studies, with high-quality measures of Na and EI, are required. PMID- 26810973 TI - Optimal fetal positioning: a theory in tatters-time to rewrite textbooks. PMID- 26810974 TI - Aetiology of lateral progression of arthritis following Oxford medial unicompartmental knee replacement: a case-control study. AB - PURPOSE: The aim of this case-control study is to assess for predictive factors that may determine development of lateral compartment progression after Oxford medial unicompartmental knee replacement. METHODS: Twenty-eight patients who were revised as a result of lateral osteoarthritis progression were matched to 52 alive and unrevised patients. Body mass index, intra-operative findings, postoperative leg alignment, meniscal bearing size and histological findings have been analysed. Radiological analysis was carried out on the immediate postoperative radiographs by two blinded observers to assess the severity of arthritis in the lateral compartment. The measurements of the components positions were converted into binary figures as to whether they were inside or outside the recommended limits for analysis. Conditional logistic regression was used to identify important predictors of progression, taking into account the case-control grouping. RESULTS: The results shows that the condition of the lateral compartment is a significant predictor for developing subsequent lateral compartment arthrosis (OR 2.627, p = 0.019). The study showed no relationship between progression of arthritis and component position (OR [0.5-1.18], p [0.21 1]). Nor have it demonstrated that BMI (OR 1.06, p = 0.61), postoperative leg alignment (OR 1.26, p = 0.636), meniscal bearing size (1.32, p = 0.307) or presence of chondrocalcinosis (OR 0.35, p = 0.36) have any association with lateral osteoarthritis progression. CONCLUSIONS: This study showed the importance of excluding radiographic evidence of lateral compartment osteoarthritis on the preoperative radiograph prior to medial unicompartmental knee replacement. We have not been able to show any relationship between progression of arthritis and component position. Level of proof Case-control study, level III. PMID- 26810975 TI - Integrating mutation and gene expression cross-sectional data to infer cancer progression. AB - BACKGROUND: A major problem in identifying the best therapeutic targets for cancer is the molecular heterogeneity of the disease. Cancer is often caused by an accumulation of mutations which produce irreversible damage to the cell's control mechanisms of survival and proliferation. Different mutations may affect these cellular anachronisms through a combination of molecular interactions which may be dynamically changing during cancer progression. It has been previously shown that cancer accumulates mutations over time. In this paper we address the problem of cancer heterogeneity by modeling cancer progression using somatic mutation and gene expression cross-sectional data. RESULTS: We propose a novel formulation of integrating somatic mutation and gene expression data to infer the temporal sequence of events from cross-sectional data. Using a mixed integer linear program we model the interaction between groups of different mutated genes and the resulting modifications at the gene expression level. Our approach identifies a partition of mutation events which gradually produce gene expression changes to a partition of genes over time. The proposed formulation is tested using both simulated data and real breast cancer data with matched somatic mutations and gene expression measurements from The Cancer Genome Atlas. First, we classify the genes as oncogenes or tumor suppressors based on the frequency of driver mutations. As expected, the most frequently mutated genes in breast cancer are PIK3CA and TP53 genes. Then, we select those genes with most frequent driver mutations and a set of genes known to play roles in cancer development. Furthermore, we apply the proposed mixed integer linear program to identify the temporal order in which genes mutate and, simultaneously, the changes they produce at the gene expression level during cancer progression. In addition, we are able to identify known causal relationships between mutations and gene expression changes in PI3K/AKT and TP53 pathways. CONCLUSIONS: This paper proposes a new model to infer the temporal sequence in which mutations occur and lead to changes at the gene expression level during cancer progression. The approach is general and can be applied to any data sets with available somatic mutations and gene expression measurements. PMID- 26810977 TI - Accuracy of 3D fluoroscopy-navigated anterior transpedicular screw insertion in the cervical spine: an experimental study. AB - PURPOSE: The technique of pedicle screw stabilization is finding increasing popularity for use in the cervical spine. Implementing anterior transpedicular screws (ATPS) in cervical spine offers theoretical advantages compared to posterior stabilization. The goal of the current study was the development of a new setting for navigated insertion of ATPS, combining the advantage of reduced invasiveness of an anterior approach with the technical advantages of navigation. METHODS: 20 screws were implanted in levels C3 to C6 of four cervical spine models (SAWBONES((r)) Cervical Vertebrae with Anterior Ligament) with the use of 3D fluoroscopy navigation system [Arcadis Orbic 3D, Siemens and VectorVision fluoro 3D trauma software (BrainLAB)]. The accuracy of inserted screws was analyzed according to postoperative CT scans and following the modified Gertzbein and Robbins classification. RESULTS: 20 anterior pedicle screws were placed in four human cervical spine models. Of these, eight screws were placed in C3, two screws in C4, six screws in C5, and four screws in C6. 16 of 20 screws (80 %) reached a grade 1 level of accuracy according to the modified Gertzbein and Robbins Classification. Three screws (15 %) were grade 2, and one screw (5 %) was grade 3. Grade 4 and 5 positions were not evident. Summing grades 1 and 2 together as "good" positions, 95 % of the screws achieved this level. Only a single screw did not fulfill these criteria. CONCLUSION: The setting introduced in this study for navigated insertion of ATPS into cervical spine bone models is well implemented and shows excellent results, with an accuracy of 95 % (Gertzbein and Robbins grade 2 or better). Thus, this preliminary study represents a prelude to larger studies with larger case numbers on human specimens. PMID- 26810978 TI - Reliability of the evaluation of posterior ligamentous complex injury in thoracolumbar spine trauma with the use of computed tomography scan. AB - PURPOSE: The AOSpine thoracolumbar (TL) spine injury classification system is based mainly on computed tomography (CT). The main purpose of this study was to evaluate the reliability of CT scan in the diagnosis of posterior ligamentous complex (PLC) injury in thoracolumbar spine trauma (TLST). METHODS: We performed a cross-sectional study of 43 patients with TLST. CT scans were evaluated independently by three spine surgeons on two separate occasions, 2 months apart. The reliability of PLC injury parameters was assessed by the Kappa coefficient (kappa) and the average percentage of these parameters was established. Injuries were classified according to the AOSpine classification as type A (compression), B (anterior and/or posterior tension band injuries) or C (dislocation) injury and the reliability of the classification was calculated. RESULTS: On average, PLC injury was identified in 91.4% of type B or C injuries. Tension band injury and dislocation were found in 90.5% of type B and 93.2% of type C injuries. The intraobserver reliability for the PLC injury parameters ranged from 0.518 to 1.000, except for increased interspinous distance (IID). Interobserver reliability ranged from 0.303 to 0.688. When the patients were evaluated as a whole, dislocation showed the highest kappa (0.656 and 0.688). When type A or B injuries were assessed, the highest kappa were found for IID (0.533 and 0.511) and tension band injury (0.486 and 0.452). The kappa for AOSpine classification was 0.526 and 0.645 in both assessments. CONCLUSIONS: In this study, the use of CT scan as the only diagnostic tool could identify PLC injury in most cases and demonstrated satisfactory reliability. Dislocation could satisfactorily diagnose type C injury, while IID was the best parameter to differentiate between type A and B injuries. PMID- 26810976 TI - Urban traffic-derived nanoparticulate matter reduces neurite outgrowth via TNFalpha in vitro. AB - BACKGROUND: The basis for air pollution-associated neurodegenerative changes in humans is being studied in rodent models. We and others find that the ultrafine particulate matter (PM) derived from vehicular exhaust can induce synaptic dysfunction and inflammatory responses in vivo and in vitro. In particular, a nano-sized subfraction of particulate matter (nPM, PM0.2) from a local urban traffic corridor can induce glial TNFalpha production in mixed glia (astrocytes and microglia) derived from neonatal rat cerebral cortex. METHODS: Here, we examine the role of TNFalpha in neurite dysfunctions induced by nPM in aqueous suspensions at 12 MUg/ml. First, we show that the proximal brain gateway to nPM, the olfactory neuroepithelium (OE), rapidly responds to nPM ex vivo, with induction of TNFalpha, activation of macrophages, and dendritic shrinkage. Cell interactions were further analyzed with mixed glia and neurons from neonatal rat cerebral cortex. RESULTS: Microglia contributed more than astrocytes to TNFalpha induction by nPM. We then showed that the threefold higher TNFalpha in conditioned media (nPM-CM) from mixed glia was responsible for the inhibition of neurite outgrowth by small interfering RNA (siRNA) TNFalpha knockdown and by TNFalpha immunoneutralization. Despite lack of TNFR1 induction by nPM in the OE, experimental blocking of TNFR1 by TNFalpha receptor blockers restored total neurite length. CONCLUSIONS: These findings implicate microglia-derived TNFalpha as a mediator of nPM in air pollution-associated neurodegenerative changes which alter synaptic functions and neuronal growth. PMID- 26810979 TI - A retrospective study to reveal the effect of surgical correction of cervical kyphosis on thoraco-lumbo-pelvic sagittal alignment. AB - PURPOSE: Recent studies suggest that cervical lordosis is influenced by thoracic kyphosis and that T1 slope is a key factor determining cervical sagittal alignment. However, no previous study has investigated the influence of cervical kyphosis correction on the remaining spinopelvic balance. The purpose of this study is to assess the effect of surgical correction of cervical kyphosis on thoraco-lumbo-pelvic alignment. METHODS: Fifty-five patients who underwent >=2 level cervical fusions for cervical radiculopathy or myelopathy were included. All patients had regional or global cervical kyphosis, which was surgically corrected into lordosis. Radiographic measurements were made using whole spine standing lateral radigraphs pre- and postoperatively to analyze various sagittal parameters. The visual analogue scale (VAS) for neck pain and the neck disability index (NDI) were calculated. The paired t test was used to compare pre- and post operative radiographic measures and functional scores. Correlations between changes in cervical sagittal parameters and those of other sagittal parameters were analyzed by Pearson's correlation method. RESULTS: Preoperative kyphosis (11.4 degrees +/- 8.3 degrees ) was corrected into lordosis (-9.3 degrees +/- 8.1 degrees ). The average fusion levels were 3.3 +/- 1.0. With increasing C2-C7 lordosis after surgery (from -3.4 degrees +/- 10.0 degrees to -15 degrees +/- 7.9 degrees ), C0-C2 lordosis decreased significantly (from -34.6 degrees +/- 8.2 degrees to -27.7 degrees +/- 8.0 degrees ) (P < 0.001). Thoracic kyphosis (from 24.8 +/- 13.9 degrees to 33.5 +/- 11.9 degrees ) and T1 slope (from 12.8 degrees +/- 7.9 degrees to 20.4 degrees +/- 5.2 degrees ) significantly increased after surgery (P < 0.001). However, other parameters did not significantly change (P > 0.05). Neck pain VAS and NDI scores (31.8 +/- 16.2) significantly improved (P < 0.001). The degree of increasing C2-C7 lordosis by surgical correction was negatively correlated with changes in both thoracic kyphosis and T1 slope (P < 0.01). CONCLUSIONS: Surgical correction of cervical kyphosis affects T1 slope and thoracic kyphosis, but not lumbo-pelvic alignment. These results indicate that the compensatory mechanisms to minimize positive sagittal malalignment of the head may occur mainly in the thoracic, and not in the lumbosacral spine. PMID- 26810980 TI - Prevalence, Awareness and Determinants of Diabetic Retinopathy in a Screening Centre in Nigeria. AB - There is a global rise in the prevalence of diabetes and this has led to a rise in the consequences of diabetes such as diabetic retinopathy (DR). The current study aims to determine the prevalence, awareness and determinants of DR among diabetics who attended a screening centre in Enugu, south-eastern Nigeria. A descriptive cross-sectional study was carried out among consenting diabetic patients who visited the centre. An interviewer-administered questionnaire was used to gather information on demographic details, the knowledge of the participants on effects of diabetes on the eye and previous care they had received for their eyes. Each participant underwent eye examination which included posterior segment examination with slit lamp biomicroscopy with +90DS lens after pupil dilation. A total of 80 eligible participants were examined. The prevalence of any DR among the participants was 32.1 % (95 % CI 20.6-43.5) whereas prevalence of proliferative diabetic retinopathy, PDR was 6.4 % and diabetic macular oedema, DME was 31.3 %. Age at onset of diabetes and duration of diabetes were the most determinant factors associated with DR (p = 0.039 and p = 0.000 respectively). Only ten (12.5 %) participants had undergone at least one specific eye examination to check for DR since they were diagnosed with diabetes. The major reason for not having had a prior screening is 'no one referred me for it' (31 participants, 44.3 %). DR is emerging as an important cause of blindness and severe visual impairment. Adequate screening programme and treatment protocol need to be set up for this population even in developing countries to prevent blindness. PMID- 26810981 TI - Patient Vertical Centering and Correlation with Radiation Output in Adult Abdominopelvic CT. AB - The purpose of this study was to determine if there is a significant effect, independent of patient size, of patient vertical centering on the current modulated CT scanner radiation output in adult abdominopelvic CT. A phantom was used to evaluate calculation of vertical positioning and effective diameter at five different table heights. In addition, 656 consecutive contrast-enhanced abdominopelvic scans using the same protocol and automatic tube current modulation settings on a Philips Brilliance 64 MDCT scanner were retrospectively evaluated. The vertical position of the patient center of mass and the average effective diameter of the scanned patient were computed using the reconstructed images. The average volume CT dose index (CTDIvol) for each scan was recorded. The mean patient center of mass y coordinate ranged from -3.7 to 6.7 cm (mean +/- SD, 2.8 +/- 1.2 cm), indicating that patients were on average positioned slightly below the scanner isocenter. There was a slight tendency for smaller patients to be mis-centered lower than larger patients. Average CTDIvol closely fit a quadratic regression curve with respect to mean effective diameter. However, the value of the regression coefficient relating CTDIvol to the patient's vertical position was nearly zero, indicating only a very slight increase in CTDIvol with patient mis-centering for the scanner used in this study. The techniques used here may be useful both for automated evaluation of proper patient positioning in CT and for estimating the radiation dose effects of patient mis-centering for any CT scanner. PMID- 26810983 TI - Combined vaginal-laparoscopic-transanal approach for reducing bladder dysfunction after conservative surgery in large deep rectovaginal endometriosis. PMID- 26810982 TI - Two members of TaRLK family confer powdery mildew resistance in common wheat. AB - BACKGROUND: Powdery mildew, caused by Blumeria graminearum f.sp. tritici (Bgt), is one of the most severe fungal diseases of wheat. The exploration and utilization of new gene resources is the most effective approach for the powdery mildew control. RESULTS: We report the cloning and functional analysis of two wheat LRR-RLKs from T. aestivum c.v. Prins- T. timopheevii introgression line IGV1-465, named TaRLK1 and TaRLK2, which play positive roles in regulating powdery mildew resistance in wheat. The two LRR-RLKs contain an ORF of 3,045 nucleotides, encoding a peptide of 1014 amino acids, with seven amino acids difference. Their predicted proteins possess a signal peptide, several LRRs, a trans-membrane domain, and a Ser/Thr protein kinase domain. In response to Bgt infection, the TaRLK1/2 expression is up-regulated in a developmental-stage dependent manner. Single-cell transient over-expression and gene-silencing assays indicate that both genes positively regulate the resistance to mixed Bgt inoculums. Transgenic lines over-expressing TaRLK1 or TaRLK2 in a moderate powdery mildew susceptible wheat variety Yangmai 158 led to significantly enhanced powdery mildew resistance. Exogenous applied salicylic acid (SA) or hydrogen peroxide (H2O2) induced the expression of both genes, and H2O2 had a higher accumulation at the Bgt penetration sites in RLK over-expression transgenic plants, suggesting a possible involvement of SA and altered ROS homeostasis in the defense response to Bgt infection. The two LRR-RLKs are located in the long arm of wheat chromosome 2B, in which the powdery mildew resistance gene Pm6 is located, but in different regions. CONCLUSIONS: Two members of TaRLK family were cloned from IGV1-465. TaRLK1 and TaRLK2 contribute to powdery mildew resistance of wheat, providing new resistance gene resources for wheat breeding. PMID- 26810984 TI - Greenlight((r)) laser and uterine fibroids. PMID- 26810985 TI - Effects of temperature, light and incubation period on production, germination and bioactivity of Trichoderma atroviride. AB - AIMS: The goal was to determine the effect of temperature, light and incubation period on production, germination and bioactivity of Trichoderma atroviride LU132 against Rhizoctonia solani. METHODS AND RESULTS: The incubation temperatures of 20, 25 or 30 degrees C were assessed on the production of T. atroviride conidia under constant light over a 25 and 50 days periods. The resulting conidia were also studied for germination and bioactivity. Conidium production was maximum at 25 degrees C after 20 days. The second peak of conidium production occurred at 45 50 days. Incubation at 25 degrees C after 15 days showed optimum production of T. atroviride LU132. Conidia produced at 30 degrees C gave the greatest germination and bioactivity in comparison with incubation at 20 or 25 degrees C. CONCLUSION: This study indicates that the temperature at which conidia of T. atroviride are produced affects germination and bioactivity. Formulations based on production of the high conidia yield may not result in optimal bioactivity and there is a trade off between quantity and quality of T. atroviride LU132 conidia. Conidium production was shown to be a continuous process, and increased under a dark/light regime. This is the first report of bimodal conidium production in a Trichoderma biological control agent (BCA), which is likely to be on 20 days cycle, and is dependent on colony age rather than abiotic factors. Conidia produced after 15 days are likely to be the most suitable for use in commercial production of this strain as a BCA. SIGNIFICANCE AND IMPACT OF THE STUDY: Most studies on Trichoderma-based BCA have only shown the effect of culture conditions on the high conidia yield regardless of conidium quality. This study is the first report on conidium quality affected by principal culture conditions for Trichoderma biological control formulations. PMID- 26810987 TI - Robotic Nissen fundoplication for gastro-oesophageal reflux disease with hiatal hernia (with video). PMID- 26810988 TI - Anticancer activity of a cis-dichloridoplatinum(ii) complex of a chelating nitrogen mustard: insight into unusual guanine binding mode and low deactivation by glutathione. AB - A pyridine ring containing a chelating nitrogen mustard ligand bis(2 chloroethyl)pyridylmethylamine hydrochloride (L2.HCl) was synthesized from bis(2 hydroxyethyl)pyridylmethylamine (L1) on reaction with thionyl chloride. Both the ligands upon reaction with cis-[PtCl2(DMSO)2] afforded square planar complexes cis-[PtCl2(L1)] (1) and cis-[PtCl2(L2)] (2) respectively. Both the complexes were characterized by NMR, IR, UV and elemental analysis. 2 crystallized in the P21/c space group. 2 shows greater solution stability than 1 in kinetic studies by 1H NMR. Both 1 and 2 bind the model nucleobase 9-ethylguanine (9-EtG) and form multiple mono-adducts. Existence of unusual N7,O6 chelated guanine bound 2 (2e) was traced. Binding studies of 2 with glutathione (GSH) show formation of a mono adduct cis-[PtCl(L2)SG] (2c), which transformed within a day to give an aziridinium ion of L2 (2b) after loss of L2. In vitro cytotoxicity of ligands, complexes and the clinical anticancer drug cisplatin show that 2 is the most potent against MCF-7, A549 and MIA PaCa2 exhibiting IC50 values of 12.6 +/- 0.8, 18.2 +/- 1.8 and 4.2 +/- 1.0 MUM respectively. The in vitro cytotoxicity of 2 against MCF-7, A549 and MIA PaCa2 was also probed in hypoxia and in the presence and absence of added GSH. Even in the presence of excess GSH in hypoxia, 2 exhibits significant cytotoxicity against MIA PaCa2 and MCF-7 with IC50 of 4.4 +/ 0.8 and 12.5 +/- 1.1 MUM respectively. Metal accumulation studies by ICP-MS display greater cellular internalization of 2, than 1 and cisplatin in MCF-7 cells. 2 arrests the cell cycle at sub G1 and G2/M phases in MCF-7 whereas cisplatin exhibits S phase arrest to be dominant with increase in concentration. Complex 2 exhibits a change in mitochondrial membrane potential, caspase activity and suggests apoptotic cell death through the intrinsic pathway. Moreover it is encouraging to find that 2 also restricts angiogenesis in chick embryo. PMID- 26810989 TI - Laparoscopic Hiatal Hernia Repair in the Elderly Patient. AB - BACKGROUND: Hiatal hernias (HH) are more common among elderly patients, with an increase in incidence with advancing age. Elderly patients frequently suffer from comorbidity, causing them to have an increased risk of perioperative mortality and morbidity. The aim of this study is to assess the safety of this procedure within elderly patients. METHODS: We performed a retrospective analysis of all patients with HH operated between July 2009 and May 2015 at two hospitals in the Netherlands specialized in antireflux surgery and HH repair. Mortality rates and short- and long-term morbidity rates were compared between patients aged under 70 years and aged over 70 years. RESULTS: A total of 204 consecutive patients underwent laparoscopic HH repair at our institutions, of whom 121 were aged under 70 years and 83 were aged over 70 years. There was no mortality intraoperatively, nor during 30-days follow-up. Intraoperative complications occurred in 7 patients aged 70 years and over, with no significant differences compared to the patients aged under 70. The 30-day morbidity rate did not significantly differ between the age groups, with an overall postoperative complication rate of 9.3 %. Only length of stay (LOS) was significantly longer in the elderly patients. Performing univariate analysis, only the occurrence of intraoperative complications was associated with 30-day morbidity. CONCLUSION: In the present study, age was not associated with increased 30-day morbidity or mortality following HH repair. Therefore, in carefully selected patients, age should not be used as an argument to withhold laparoscopic HH repair. PMID- 26810990 TI - Port Site Recurrences Following Laparoscopic Liver Resection for Hepatocellular Carcinoma. PMID- 26810991 TI - Delay Between Onset of Symptoms and Surgery in Acute Appendicitis Increases Perioperative Morbidity: A Prospective Study. AB - BACKGROUND: Despite significant progress in surgery, controversy persists about timing of appendectomy. Objective of this prospective observational study was to determine associations between time interval from onset of symptoms in appendicitis to appendectomy and postoperative complications. METHODS: After institutional review board approval, all adult consecutive patients subjected to emergency appendectomy between 1/9/2013 and 1/12/2014 were prospectively enrolled. Data collection included demographics, open vs. laparoscopic appendectomy, comprehensive complication index (CCI), and 30-day follow-up. To determine time-dependent associations between delay of surgery and complications all patients were stratified into subgroups based on 12-h time intervals from onset of abdominal pain to surgery. Primary outcome was complications per CCI in correlation to delay from symptoms to appendectomy. Secondary outcomes included duration of surgery, hospital length of stay (HLOS), and incidence of complication within 30-day follow-up. RESULTS: A total of 266 patients with a mean age of 35.4 +/- 14.8 years met inclusion criteria. Overall, 83.1 % of patients were subjected to laparoscopic appendectomy. Delay to surgery in 12-h increments showed stepwise-adjusted increase in complications per CCI (adj. P = 0.037). Also, delay to appendectomy increased significantly duration of surgery and HLOS, respectively (adj. P < 0.001 and adj. P < 0.001). Overall, 5.7 % of patients developed a surgical site infection after hospital discharge. CONCLUSION: Extended time interval from the onset of initial symptoms to appendectomy is associated with increased complications per CCI, duration of surgery, and HLOS in acute appendicitis. Prompt appendectomy in acute appendicitis is warranted. PMID- 26810992 TI - Oral cancer intraoperative detection by topically spraying a gamma-glutamyl transpeptidase-activated fluorescent probe. PMID- 26810993 TI - Correction. PMID- 26810994 TI - Eliciting patient preferences, priorities and trade-offs for outcomes following kidney transplantation: a pilot best-worst scaling survey. AB - OBJECTIVES: Eliciting preferences and trade-offs that patients may make to achieve important outcomes, can assist in developing patient-centred research and care. The pilot study aimed to test the feasibility of a case 2 best-worst scaling survey (BWS) to elicit recipient with kidney transplantation preferences after transplantation. DESIGN: Preferences for graft survival and dying, cancer, cardiovascular disease, diabetes, infection and side effects (gastrointestinal, weight-gain and appearance) were assessed in recipients with transplantation using a BWS (20 scenarios of nine outcomes). Participants chose 'best' and 'worst' outcomes. Responses were analysed using a multinomial logit model. Selected participants were interviewed. OUTCOMES: Attribute coefficients and survey completion error rates. RESULTS: 81 recipients with transplantation were approached, and 39 (48%), mean age 50.5 years, completed the BWS. 4 (10%) surveys were invalid with major errors and of 35 remaining, 7 of 1400 (0.5%) choices were missing. -23 (59%) took >20 min to complete the survey. 1 was unable to finish, and 1 did not understand the survey. 2 (5%) found it very hard and 14 (35%) moderately hard. Most attribute coefficients were significant (p<0.05) and showed face validity. Graft survival was most important with normalised coefficients from 1 (95% CI 0.89 to 1.11) to 0.06 (95% CI -0.03 to 0.16) for 30 and 1 year duration, respectively. Attribute level coefficients decreased with increasing risk of adverse outcomes. Error rates of 20% and 2% were estimated for dominant attributes '100% risk of dying' and '30 years graft survival', respectively. 7 participants were interviewed regarding counterintuitive selection of '100% risk of dying' as a 'best' outcome. Misunderstanding, not linking dying to graft survival and aversion to dialysis were reasons given. CONCLUSIONS: Recipients with transplant recipients successfully completed a complex case 2 BWS with attribute coefficients having face validity with respect to duration of graft survival and risk of adverse outcomes. Areas for refinement to reduce complexity in design have been identified. PMID- 26810995 TI - Sociodemographic, home environment and parental influences on total and device specific screen viewing in children aged 2 years and below: an observational study. AB - OBJECTIVE: This study aimed to investigate total and device-specific screen viewing (SV) and its determinants in children aged 2 years and below. DESIGN: Cross-sectional study conducted in February 2014. SETTING: Well-child clinics in Singapore national polyclinics. PARTICIPANTS: Parents of children (Singapore citizens or permanent residents) aged 2 years and below were enrolled during routine clinic visits. Out of 794 eligible parent-child dyads, 725 (91.3%) provided informed consent and were included in the analysis. MAIN OUTCOME MEASURES: Device-specific information on SV and determinants was ascertained using interviewer-administered survey questionnaires. The prevalence and duration of aggregate and device-specific SV were reported. Associations with potential determinants were investigated using multiple logistic regression analysis. A p value less than 0.05 was considered statistically significant. RESULTS: The prevalence of daily SV and SV >= 2 h/day constituted 53.5% and 16.3%, respectively. The majority of children aged 18-24 months (88.2%) engaged in daily SV. TVs and mobile devices were the most commonly used screen devices, followed by computers and video consoles. In multivariable analysis, younger child age, Chinese ethnicity and setting rules on time of SV were strongly and consistently associated with lower levels of any SV and SV >= 2 h/day. Parental knowledge of SV recommendations and less parental SV were additionally associated with lower levels of SV >= 2 h/day. The number of screen devices was not associated with children's SV. CONCLUSIONS: In contrast to recommendations, SV prevalence in children aged less than 2 years is high and appears to increase steadily across age groups. TVs and mobile devices are most frequently used. Improving parental knowledge of SV recommendations, reducing parental SV and especially the implementation of strict rules on SV time could be successful strategies to reduce SV in young children. PMID- 26810997 TI - A cohort study of trends in the prevalence of pregestational diabetes in pregnancy recorded in UK general practice between 1995 and 2012. AB - OBJECTIVE: To describe the characteristics of pregnant women with and without pregestational diabetes and to estimate the prevalence of pregestational diabetes in pregnant women recorded in a UK primary care database. METHODS: The data source for this study is The Health Improvement Network (THIN) primary care database. Pregnant women with and without diabetes aged 16 years and over were identified using diagnostic Read codes and prescriptions for antidiabetics from medical records. Data were examined on: age, body mass index (BMI), social deprivation, smoking, ethnicity and glycaemic control. The prevalence of pregestational diabetes was calculated by diabetes type and calendar year between 1995 and 2012. RESULTS: Data from 400,434 pregnancies suggests that women with pregestational diabetes were: older (median 29, 32 vs 29 years for type 1, type 2 and without diabetes, respectively), had higher BMI (median 25.0, 30.4 vs 23.9 k/m(2) for type 1, type 2 and without diabetes, respectively) and were registered with a general practice for longer than pregnant women without diabetes. The prevalence of type 1 diabetes in pregnancy increased from 1.56 to 4.09 per 1000 pregnancies between 1995 and 2015. For type 2 diabetes the increase was from 2.34 to 5.09 per 1000 pregnancies between 1995 and 2008 followed by a more rapid increase to 10.62 per 1000 pregnancies by 2012. CONCLUSIONS: Pregnant women with pregestational diabetes were older, had higher BMI and were registered for longer than women without diabetes. The prevalence of type 1 and type 2 diabetes increased in pregnancy. The prevalence of type 2 diabetes rose more rapidly with a marked increase after 2008. PMID- 26810996 TI - Infant feeding and risk of developing celiac disease: a systematic review. AB - OBJECTIVE: To review the evidence for the association of breast feeding, breastfeeding duration or the timing of gluten introduction and the later development of celiac disease (CD). DESIGN: Systematic review. METHODS: We searched MEDLINE, via PubMed, EMBASE and Web of Science, for studies published up to 31 August 2015 investigating the association of breastfeeding duration, breast feeding at the moment of gluten introduction or the timing of gluten introduction and the later development of CD. Prospective studies had to enrol infants/children at high risk of CD. For retrospective studies, participants had to be children or adults with CD. The paper quality was assessed by means of a GRADE score and the bias risk was assessed by the Newcastle-Ottawa Scale (for observational cohort studies) and Cochrane Collaboration's tool (for randomised trials). RESULTS: Out of 149 retrieved papers, 48 were considered in depth and 16 were included in this review (9 were prospective and 2 were interventional). We found that neither duration of breastfeeding nor breastfeeding at time of gluten introduction nor the delayed introduction of gluten during weaning were effective in preventing later development of CD. CONCLUSIONS: Currently, there is no evidence on the optimal breastfeeding duration or the effects of avoiding early (<4 months of age) or late (>= 6 or even at 12 months) gluten introduction in children at risk of CD. Accordingly, no specific general recommendations about gluten introduction or optimal breastfeeding duration can be presently provided on evidence-based criteria in order to prevent CD. PMID- 26810998 TI - Wearable technologies in osteoarthritis: a qualitative study of clinicians' preferences. AB - OBJECTIVE: This study investigates clinicians' views of health-related wearable technologies in the context of supporting osteoarthritis (OA) long-term management. Clinicians' preferences are critical in identifying realistic implementation strategies for such technologies. DESIGN: Qualitative study incorporating an inductive thematic analysis applied to identify key themes from clinicians' responses. PARTICIPANTS: Clinicians, including 4 general practitioners, 4 physiotherapists and 5 orthopaedic surgeons were interviewed. SETTING: The study was conducted in a University setting. RESULTS: Participants all agreed wearable technologies could positively complement their role and enhance their relationship with patients. Perceived benefits of wearable technologies included monitoring patients' progress, treatment evaluation, monitoring compliance and informing clinical decision-making. The device should be designed to provide objective data of patients' locomotion capability in an easy and timely fashion via a simple interface. Data should be available to both clinicians and patients to provide them with the motivation to achieve clinical goals and allow them to take ownership of their treatment. The use of technology was also seen as a way to more effectively plan treatment and manage patients' contact time saving time and cost. CONCLUSIONS: Findings support the use of wearable technologies to enhance current OA management and suggest clinical uses. Adoption of technologies could have implications on the effectiveness of treatment provided overcoming current barriers, in particular compliance with treatment. PMID- 26810999 TI - ATTIRE: Albumin To prevenT Infection in chronic liveR failurE: study protocol for a single-arm feasibility trial. AB - INTRODUCTION: Circulating prostaglandin E2 levels are elevated in acutely decompensated cirrhosis and have been shown to contribute to immune suppression. Albumin binds and inactivates this hormone. Human albumin solution could thus be repurposed as an immune restorative drug in these patients.This feasibility study aims to determine whether it is possible and safe to restore serum albumin to >30 g/L and maintain it at this level in patients admitted with acute decompensated cirrhosis using repeated 20% human albumin infusions according to daily serum albumin levels. METHODS AND ANALYSIS: Albumin To prevenT Infection in chronic liveR failurE (ATTIRE) stage 1 is a multicentre, open label dose feasibility trial. Patients with acutely decompensated cirrhosis admitted to hospital with a serum albumin of <30 g/L are eligible, subject to exclusion criteria. Daily intravenous human albumin solution will be infused, according to serum albumin levels, for up to 14 days or discharge in all patients. The primary end point is daily serum albumin levels for the duration of the treatment period and the secondary end point is plasma-induced macrophage dysfunction. The trial will recruit 80 patients. Outcomes will be used to assist with study design for an 866 patient randomised controlled trial at more than 30 sites across the UK. ETHICS AND DISSEMINATION: Research ethics approval was given by the London-Brent research ethics committee (ref: 15/LO/0104). The clinical trials authorisation was issued by the medicines and healthcare products regulatory agency (ref: 20363/0350/001-0001). RESULTS: Will be disseminated through peer reviewed journals and international conferences. Recruitment of the first participant occurred on 26/05/2015. TRIAL REGISTRATION NUMBER: The trial is registered with the European Medicines Agency (EudraCT 2014-002300-24) and has been adopted by the NIHR (ISRCTN 14174793). This manuscript refers to V.4.0 of the protocol; Pre results. PMID- 26811002 TI - Cinnamaldehyde Characterization as an Antibacterial Agent toward E. coli Metabolic Profile Using 96-Blade Solid-Phase Microextraction Coupled to Liquid Chromatography-Mass Spectrometry. AB - Sampling and sample preparation plays an important role in untargeted analysis as it influences final composition of the analyzed extract and consequently reflection of the metabolome. In the current work, mechanism of bactericidal action of cinnamaldehyde (CA) against Escherichia coli (E. coli) during bacteria growth applying high-throughput solid-phase microextraction in direct immersion mode coupled to a high-performance liquid chromatography-mass spectrometry system was investigated. Numerous discriminant metabolites due to CA addition to the bacteria culture were mapped in the E. coli metabolic pathways. We propose new metabolic pathways confirming that CA acts as an oxidative stress agent against E. coli. The results of the current research have successfully demonstrated that CA changes the bacterial metabolism through interactions with different biochemical families such as proteins, nucleic acids, lipids, and carbohydrates, which needs further validation by proteomics and transcriptomics studies. The results presented here show the great potential of the novel approach in drug discovery and food safety. PMID- 26811001 TI - Diagnostic coronary angiography: initial results of a simulation program. AB - BACKGROUND: The use of simulator-based teaching in cardiology has unfortunately lagged behind other procedural specialties. This study investigates the utility of a simulator-based training program for fellows in cardiovascular disease with no prior experience in diagnostic coronary angiography. METHODS: First-year cardiology fellows at University of Illinois-Chicago (UIC) using AngioMentorTM simulators completed benchmark cases requiring basic coronary engagement. Subsequently, benchmark cases were completed one day later and at 9months following 2-3months of training in the cardiac catheterization lab. In addition, 1st year cardiology fellows were compared to 3rd year fellows. Objective measures assessed from benchmark cases were total procedural time, total contrast used, and total fluoroscopy time. RESULTS: All 1st year fellows improved their total time to complete the benchmark case from initial to second attempt one day later (14:56 on Day 1, 8:30 on Day 2, P=0.03). Total contrast used (60mL on Day 1, 39mL on Day 2, P=0.11) and total fluoroscopic time (6:30 on Day 1 and 4:26 on Day 2, P=0.16) also both decreased. Overall procedure time and contrast use were similar among 1st and 3rd year fellows after simulation training. Decreases in procedure and fluoroscopy time were maintained in 1st year fellows after 2-3months of training. CONCLUSION: Fellows displayed technical and procedural improvement at diagnostic coronary angiography in a short period of time and in a safe, patient free environment. In this study, a computer-based simulator was successfully incorporated into a first year cardiovascular fellowship curriculum and represents a contemporary means to provide the fellow increased procedural training without added risk to the patient. SENTENCE SUMMARY: The use of simulator-based teaching in cardiology has unfortunately lagged behind other procedural specialties. In this study, a computer-based simulator was successfully incorporated into a first year cardiovascular fellowship curriculum. A firm teaching curriculum is the next step towards implementing this modality in an organized fashion. PMID- 26811000 TI - Decrease of TET2 expression and increase of 5-hmC levels in myeloid sarcomas. AB - BACKGROUND: Myeloid sarcoma is a tumor mass that consists of myeloblasts or immature myeloid cells at an extramedullary site. Pathological diagnosis is very difficult based on morphology if systemic signs of disease are absent. The subtype of myeloid sarcoma is also minimally identifiable in the histological picture. FINDINGS: We investigated 18 paraffin-embedded myeloid sarcoma samples, and our immunohistochemical data confirmed the relevance of some key markers for the diagnosis and subclassification of myeloid sarcoma. CD34 was found as a marker in 67% of the myeloid sarcoma cases, and CD34 was positive in all immature types of myeloid sarcoma. CD68 was found in 83% of the myeloid sarcoma cases, but CD68 was most identified in the differentiated type of myeloid sarcoma. Myeloperoxidase (MPO) was positive in all myeloid sarcomas. Notably, the reactivity of MPO in the blastic subtype was much lower in myeloid sarcomas. CD117 reactivity was found in 67% of myeloid sarcomas. Ten-eleven translocation 2 (TET2) protein exhibited significant negative reactivity in 88% of the cases, and 5-methylcytosine (5-hmC) was significantly positive in the nucleus in 100% of the cases. CONCLUSIONS: Our findings indicated that an immunohistochemical panel that included MPO, CD68 and CD34 could be used for the detection of blastic, differentiated and immature types of myeloid sarcoma. Changes in novel epigenetic regulators, including the loss of TET2 and gain of 5-hmC, as characteristics of myeloid malignancies may be useful novel markers of myeloid sarcoma. PMID- 26811003 TI - Hole-Burning Spectroscopy on Excitonically Coupled Pigments in Proteins: Theory Meets Experiment. AB - A theory for the calculation of resonant and nonresonant hole-burning (HB) spectra of pigment-protein complexes is presented and applied to the water soluble chlorophyll-binding protein (WSCP) from cauliflower. The theory is based on a non-Markovian line shape theory ( Renger and Marcus J. Chem. Phys. 2002 , 116 , 9997 ) and includes exciton delocalization, vibrational sidebands, and lifetime broadening. An earlier approach by Reppert ( J. Phys. Chem. Lett. 2011 , 2 , 2716 ) is found to describe nonresonant HB spectra only. Here we present a theory that can be used for a quantitative description of HB data for both nonresonant and resonant burning conditions. We find that it is important to take into account the excess energy of the excitation in the HB process. Whereas excitation of the zero-phonon transition of the lowest exciton state, that is, resonant burning allows the protein to access only its conformational substates in the neighborhood of the preburn state, any higher excitation gives the protein full access to all conformations present in the original inhomogeneous ensemble. Application of the theory to recombinant WSCP from cauliflower, reconstituted with chlorophyll a or chlorophyll b, gives excellent agreement with experimental data by Pieper et al. ( J. Phys. Chem. B 2011 , 115 , 4053 ) and allows us to obtain an upper bound of the lifetime of the upper exciton state directly from the HB experiments in agreement with lifetimes measured recently in time domain 2D experiments by Alster et al. ( J. Phys. Chem. B 2014 , 118 , 3524 ). PMID- 26811004 TI - Eating Behaviors and Weight Development in Obesity-Prone Children and the Importance of the Research of Albert J. Stunkard. AB - Albert J. Stunkard, MD, was an internationally recognized leader and pioneer in the field of obesity and eating disorders research. He was also among the first scientists to study eating phenotypes and early life risk factors for childhood obesity at a time when childhood obesity prevalence rates were still comparatively low. The aim of this review is to highlight select findings from the work of Albert J. Stunkard which significantly advanced our understanding of eating traits of children with a different familial predisposition to obesity and genetic and environmental influences on weight outcomes. Collectively, Stunkard's early work on childhood obesity had a significant impact on the field of ingestive behavior and obesity research in that he was one of the first investigators who pointed to genetic influences underlying behavioral eating traits and child weight status. His work also inspired numerous subsequent investigations on the relative contributions of specific genes (e.g., polymorphisms in the fat mass and obesity-associated (FTO) gene) on individual differences in child eating traits (e.g., satiety responsiveness, eating in the absence of hunger) and body weight. PMID- 26811005 TI - Obesity Stigmatization and the Importance of the Research of A.J. Stunkard. AB - Obese individuals face weight-based stigmatization and discrimination in virtually all areas of life. These stigmatizing experiences can lead to detrimental psychological, physical, and societal consequences and may further perpetuate the increasing prevalence of obesity. A. J. Stunkard was one of the first medical professionals to identify and address the serious ramifications of obesity stigmatization on both individual and societal levels. Throughout the last half-century, Stunkard contributed numerous findings and publications to the field of obesity stigmatization. His work laid the foundation and direction for important areas of current research, such as the cultural influences on weight bias, stigmatization among healthcare professionals, weight stigma among children, and the internalization of weight bias by obese individuals. His contributions have had an important influence on the current directions of these fields. PMID- 26811007 TI - Assessing the Stability of Depression in College Students. AB - Two different approaches are used to assess the one-month stability of depressive affect in college students. First, a high retest correlation is demonstrated for a latent depressive affect construct using self-reports from the previous month on the Beck Depression Inventory, the Center for Epidemiological Studies Depression Scale, and Zung's Self-Rating Depression Scale. This is true although the corresponding stabilities for individual scales are only moderate. Second, the predictive validity of depressive categorization based on these scales is examined using logistic regression techniques. Depressive categorizations are best predicted from the corresponding depressive categorization on the same scale at Time 1. There is little additional across-scale predictive information in the assessment of depressive categorization; this again suggests that a single factor model is most appropriate. Further, the association between assessments of dysphoric affect over one month in college students is less than previously established longitudinal associations between dysphoric affect categorizations over one year in older adult samples. This suggests that college students may be more affectively volatile than adults. PMID- 26811008 TI - Are Semantic Response Scales Equivalent? AB - Three frequently used response formats -- Likert, semantic-differential and single anchor (Stapel) -- are compared via analysis of covariance structures. The cumulative results based on four data sets provided evidence inconsistent with previous research suggesting that these formats are interchangeable. Consistently across studies, the semantic-differential format is most preferred while in most cases the Stapel format is least preferred. PMID- 26811006 TI - Weight-Related Dietary Behaviors in Young Adults. AB - The origins of the obesogenic environment date back to the early 1980s. This means that young adults i.e., those aged 18 to 35 years, have only ever experienced a food milieu that promotes obesity. Indeed, younger generations are becoming heavier sooner than their parents in developed countries, such as the USA. Young adults demonstrate food consumption patterns and dietary behaviors implicated in an excessive gain of body fat. They are the highest consumers of fast food and sugar-sweetened beverages among adult age groups and the lowest consumers of fruit and vegetables. Younger adults are meal skippers but may consume more energy from snacks than older adults. So that the gains made in stemming obesity in childhood are not undone during young adulthood, prevention programs are needed. This review highlights areas for consideration in planning such programs. PMID- 26811009 TI - The Multidimensionality of the Rotter I-E Scale and its Higher-order Structure: An Application of Confirmatory Factor Analysis. AB - Rotter (1966, 1975) concluded that responses to his Internal-External (I-E) scale were unidimensional, or at least that one general factor explained most of the variance in the total score. The purpose of the present investigation is to examine the factorial structure of the original Rotter scale. A review of 20 published factor analyses indicated that the scale is not unidimensional, that not even two or three factors may be able to adequately explain responses to the scale, and that six distinguishable factors have been identified. Confirmatory factor analyses indicated that a five-factor model provided an adequate fit to data from the present investigation, but that alternative models with fewer factors or a simpler structure did not fit the data as well. However, a single higher-order factor was able to explain much of the variance in the lower-order factors and also provided a reasonable fit to the data. Hence, while there is strong evidence against the unidimensionality of the Rotter scale, the findings suggest that the first-order factors do define a single higher-order construct that may represent the generalized IE construct that Rotter originally hypothesized. Nevertheless, the continued reliance of locus of control research on the Rotter scale and on global measures of the construct may be counterproductive. PMID- 26811010 TI - A Factorial Evaluation of Effects of Model Specification and Error on Parameter Estimation in a Structural Equation Model. AB - In an experiment manipulating artificial data in a factorial design, model misspecification and varying levels of error in measurement and in model structure are shown to have significant effects on LISREL parameter estimates in a modified peer influence model (Duncan, Haller & Portes, 1971). The extent of error present in both the measurement and the model have significant direct effects on estimated parameter values, and the two sorts of error interact as well. In specification, incorrect omission of parameters seems to have more impact on parameter error than does incorrect inclusion of parameters. PMID- 26811011 TI - Masculinity, Femininity and Androgyny: Their Relations With Multiple Dimensions of Self-Concept. AB - Masculinity (M) and femininity (F) were related to multiple dimensions of self concept in responses from 962 high school students. Androgyny theory predicts that both M and F will contribute positively and uniquely to self-concept, but previous research, typically relying on undifferentiated self-concept measures, has found the unique contribution of F to be nil. In contrast the present investigation found that M and F each contributed positively and uniquely to the prediction of well differentiated facets of self-concept. Consistent with a new model to explain MF/self-concept relations, the differentiated additive model, the relative contribution of M and F varied substantially depending on the area of self-concept; F contributed more positively to the self-concept facets for which girls had higher self-concepts than boys, and in some areas the contribution of F was more positive than the contribution of M. Contrary to predictions for interactive androgyny models and the sex-typed model, M-by-F interactions were not significant, and the effects of M, F and M-by-F did not depend on gender. The social desirability of MF items, whether they were negatively or positively valued, was more highly correlated with the self-concept responses than whether the items were M or F. PMID- 26811012 TI - A Review of STRATGRAPHICS. PMID- 26811013 TI - Panoptic clinical review of the current and future treatment of relapsed/refractory T-cell lymphomas: Peripheral T-cell lymphomas. AB - Peripheral T-cell lymphomas (PTCLs) tend to be aggressive and chemorefractory, with about 70% of patients developing relapsed/refractory disease. Prior to 2009, chemotherapies were the only options for relapsed/refractory PTCL, other than hematopoietic transplants. However, chemotherapy only improves survival by about 1 month compared with palliation. Four drugs are now approved in the US to treat relapsed/refractory PTCL: pralatrexate, romidepsin, belinostat, and brentuximab vedotin (for systemic anaplastic large cell lymphoma [sALCL]). Response rates with pralatrexate, romidepsin, and belinostat range from 25 to 54% in mixed relapsed/refractory PTCL populations, while 86% of sALCL patients respond to brentuximab vedotin. Here, we critically evaluate the evidence supporting the current drug treatment of relapsed/refractory PTCL, and look to the future to see how the treatment panorama may change with the advent of new targeted therapies, some of which (e.g., alisertib in PTCL and mogamulizumab in CCR4-positive adult T cell leukemia/lymphoma) are already in phase 3 trials. PMID- 26811014 TI - Panoptic clinical review of the current and future treatment of relapsed/refractory T-cell lymphomas: Cutaneous T-cell lymphomas. AB - Primary cutaneous T-cell lymphomas (CTCLs), such as mycosis fungoides and Sezary syndrome, are a rare group of non-Hodgkin lymphomas, usually treated using a multimodal approach. Unfortunately, many patients go on to develop relapsed/refractory disease. Systemic treatment for relapsed/refractory CTCL has historically relied on chemotherapies and interferons, and while active, responses are often short-lived. Three drugs are now approved in the US to treat relapsed/refractory CTCL including the oral retinoid, bexarotene, and histone deacetylase inhibitors, romidepsin and vorinostat. Although response rates are typically <35%, romidepsin and vorinostat can induce some durable responses in heavily pretreated patients and alleviate bothersome symptoms, such as pruritus. New studies indicate that the anti-CD30 antibody-drug conjugate brentuximab vedotin, anti-CCR4 antibody mogamulizumab, and fusion protein immunotoxin A dmDT390-bisFv(UCHT1) may be particularly active in this setting. In this paper, we present an exhaustive review of the clinical data on current and possible future drug treatment options for relapsed/refractory CTCL. PMID- 26811015 TI - [The suitability of therapeutic effort: An end-of-life strategy]. AB - End-of-life treatment and attention to the needs of relatives are not adequate for several reasons: Society denies or hides the death; it is very difficult to predict it accurately; treatment is frequently fragmented between different specialists, and there is insufficient palliative medicine training, including communication skills. There are frequent conflicts with decisions made at the end of life, particularly the suitability of therapeutic effort. The attitude of professionals on the adequacy of therapeutic effort is not homogenous, and varies depending on the specialty, experience, and beliefs. Many doctors are still afraid of inconveniencing patients. Primary care is in a privileged position to approach the life and values of our patients and their families, and not just the disease, which makes it the right place to guide and advise the patient on the preparation and registration of living wills. PMID- 26811017 TI - What speeds up the internal clock? Effects of clicks and flicker on duration judgements and reaction time. AB - Four experiments investigated the effect of pre-stimulus events on judgements of the subjective duration of tones that they preceded. Experiments 1 to 4 used click trains, flickering squares, expanding circles, and white noise as pre stimulus events and showed that (a) periodic clicks appeared to "speed up" the pacemaker of an internal clock but that the effect wore off over a click-free delay, (b) aperiodic click trains, and visual stimuli in the form of flickering squares and expanding circles, also produced similar increases in estimated tone duration, as did white noise, although its effect was weaker. A fifth experiment examined the effects of periodic flicker on reaction time and showed that, as with periodic clicks in a previous experiment, reaction times were shorter when preceded by flicker than without. PMID- 26811019 TI - Early Maternal Reflective Functioning and Infant Emotional Regulation in a Preterm Infant Sample at 6 Months Corrected Age. AB - OBJECTIVE: This study investigated the influence of maternal reflective functioning (RF) on 6-month-old infants' emotional self-regulating abilities in preterm infant-mother dyads. METHODS: 25 preterm (gestational age 28-34.5 weeks) infants' affect, gaze toward mother, and self-soothing behaviors (thumb-sucking and playing with clothing) were measured during the still-face procedure at 6 months corrected age. Maternal RF was measured at 7-15 days post-delivery using the Parent Development Interview. RESULTS: Infants with high RF mothers showed the most negative affect during the still-face episode (M = 21.33s, SE = 5.44), whereas infants with low RF mothers showed the most negative affect in the reunion episode (M = 18.14s, SE = 3.69). Infants with high RF mothers showed significantly more self-soothing behaviors when distressed (Ms > 14.5s) than infants with low RF mothers (Ms < 1s), p's < .01. CONCLUSION: Maternal RF was associated with infants' self-regulating behavior, providing preliminary evidence for the regulatory role of maternal RF in preterm infants' emotion regulation capacity. PMID- 26811020 TI - Robot-assisted partial nephrectomy in 95 consecutive patients: Oncological and functional outcomes at 3 years of follow-up. AB - BACKGROUND: We present the oncological and functional results from a series of 43 patients with renal tumours, treated consecutively with robot-assisted partial nephrectomy (RPN). MATERIALS AND METHOD: Between 2010 and 2014, we performed 95 RPNs. To assess the results, we included only those patients (n=43) who had a minimum follow-up of 2 years. A descriptive analysis was conducted of the demographic characteristics and perioperative variables. We employed Kaplan-Meier curves to assess overall survival, cancer-specific survival and recurrence-free survival. RESULTS: The patients' mean age was 53.1+/-13.5 years. The mean preoperative tumour size was 3.7+/-2.3cm. The mean surgical time was 102.2+/ 37.1min. The mean ischemia time was 21.27+/-7.74minutes, with a median intraoperative bleeding volume of 150mL (IQR, 87.5-425). There was a 7% rate of postoperative complications (Clavien>=III). There was no mortality. The average Furhman grade was 2.5+/-0.56. There were no positive surgical margins or local recurrences. The median follow-up was 38+/-8 months, with an overal survival, recurrence-free survival and cancer-specific survival of 100% at 3 years of follow-up. The recurrence-free survival was 92,3% at 48 months of follow-up. The mean preoperative glomerular filtration rate was 91.04+/-28.17mL/min/1.73m(2), and the postoperative rate was 89.9+/-27.69mL/min/1.73m(2), with a nonsignificant reduction (P=.74). CONCLUSIONS: The functional and oncological results of our series confirm the safety and efficacy of RPN. RPN offers optimal preservation of renal function and oncological control in the medium term. PMID- 26811021 TI - Initial validation of a training program focused on laparoscopic radical nephrectomy. AB - OBJECTIVE: To assess a training model focused on laparoscopic nephrectomy. MATERIAL AND METHODS: 16 residents participated in the study, who attended a training program with a theoretical session (1hour) and a dry (7hours) and a wet lab (13hours). During animal training, the first and last nephrectomies were assessed through the completion time and the global rating scale "Objective and Structured Assessment of Technical Skills" (OSATS). Before and after the course, they performed 3 tasks on the virtual reality simulator LAPMentor (1) eye-hand coordination; 2) hand-hand coordination; and 3) transference of objects), registering time and movement metrics. All participants completed a questionnaire related to the training components on a 5-point rating scale. RESULTS: The participants performed the last nephrectomy faster (P<.001) and with higher OSATS scores (P<.001). After the course, they completed the LAPMentor tasks faster (P<.05). The number of movements decreased in all tasks (1) P<.001, 2) P<.05, and 3) P<.05), and the path length in tasks 1 (P<.05) and 2 (P<.05). The movement speeds increased in tasks 2 (P<.001) and 3 (P<.001). With regards to the questionnaire, the usefulness of the animal training and the necessity of training on them prior to their laparoscopic clinical practice were the questions with the highest score (4.92+/-.28). CONCLUSIONS: The combination of physical simulation and animal training constitute an effective training model for improving basic and advanced skills for laparoscopic nephrectomy. The component preferred by the urology residents was the animal training. PMID- 26811022 TI - Impact of daily number of urgency urinary incontinence episodes on overactive bladder patient reported outcomes. AB - OBJECTIVE: To explore the impact of urgency urinary incontinence (UUI) on well being in non-institutionalized patients with overactive bladder (OAB) in a community sample. METHODS: A cross-sectional web-based study was conducted in the general population, including males and females, >18 years of age. Patients with probable OAB were identified using a validated algorithm together with a score >=8 on the OAB-V8 scale. Presence of coping behavior was considered determinant for the clinical diagnosis of OAB. Individual well-being was determined through a battery of patient-reported outcomes (PRO) measurements including assessment of health-related quality of life (EQ-5D), sleep disturbances (MOS Sleep), and life satisfaction (LISAT-8). Patients were grouped according to the number of daily UUI episodes (UUI severity): 0 (dry OAB),1, 2-3, or >=4. Multivariate analysis to evaluate factors independently affecting quality of life was undertaken. RESULTS: A total of 396 patients (52.5% women, mean age: 55.3 [11.1] years, OAB-V8 mean score: 14.5 [7.9]) out of 2035 subjects participating from the general population met the criteria for OAB: 203 (51.3%) with 0episodes, 119 (30.1%) with 1, 52 (13.1%) with 2 or 3, and 22 (5.6%) with >=4 episodes. A statistically significant linear adjusted association was found between number of UUI episodes and PRO scores. Participants with more episodes had poorer health profiles and self evaluated quality of life, worse life satisfaction, and more sleep disturbances and fewer hours of sleep per night. Number of incontinence episodes was independent factor to affect quality of life using both LISAT-8 and MOS questionnaires. CONCLUSION: Severity of UUI was significantly associated with poorer individual well-being in subjects with OAB in a community sample in Spain. PMID- 26811023 TI - Outcomes of laparoscopic adrenalectomy Conventional technique versus laparo endoscopic single-site surgery. AB - OBJECTIVE: Perform a comparative analysis of the outcomes of conventional laparoscopic adrenalectomy (LC) and the newly introduced laparo-endoscopic single site surgery (LESS) over ten years. MATERIAL AND METHOD: We retrospectively reviewed the experience of a single surgeon from our medical centre with laparoscopic adrenalectomy, either through LC or LESS, with 75 patients between August 2005 and June 2015. Here we describe: age, sex, size, lateralization, preoperative diagnosis, total operating time, intraoperative bleeding, conversion to open surgery, mean hospital stay, intra- and postoperative complications and histopathology report. We used Fischer's and the Chi-squared tests to compare categorical data and Student's T-test for a comparison of the means with a normal distribution. Statistical significance was determined when p<0.05. RESULTS: LC was performed in 51 patients, and LESS in 24 patients. No statistical significance was found for total operating time (LC: 103.9+/-13.21min vs. LESS: 101.46+/-13.65min; p=0.07), estimated bleeding (LC: 258.82+/-136.92cc vs. LESS: 131,25+/-36,74cc; p=0.46), intraoperative complications (5 cases in LC, none in LESS; p=0.47), nor for postoperative complications (two in LC vs. one in LESS; p=0.69), as catalogued according to the modified Clavien classification system. We detected a statistical significance difference in the comparisons of the mean hospital stay, which was reduced in LESS (LC: 3.55+/-0.69 days vs. LESS: 2.21+/ 0.31 days; p=0.01). CONCLUSIONS: Adrenalectomy with LC is the approach of choice for surgical treatment of adrenal pathologies. The LESS technique is safe, improves the cosmetic results, and does not increase mortality if performed by experienced teams. PMID- 26811024 TI - One SNP at a Time: Moving beyond GWAS in Psoriasis. AB - Although genome-wide association studies have revealed important insights into the global genetic basis of psoriasis, the findings require further investigation. At present, the known genetic risk loci are largely uncharacterized in terms of the variant or gene responsible for the association, the biological pathway involved, and the main cell type driving the pathology. This review primarily focuses on current approaches toward gaining a complete understanding of how these known genetic loci contribute to an increased disease risk in psoriasis. PMID- 26811025 TI - Unusually slow intramolecular proton transfer dynamics of 4'-N,N-dimethylamino-3 hydroxyflavone in high n-alcohols: involvement of solvent relaxation. AB - Excited state intramolecular proton transfer (ESIPT) time-constants of 4'-N,N dimethylamino-3-hydroxyflavone (DMA3HF) in high n-alcohols--1-butanol, 1-hexanol and 1-decanol--were measured to be 90 ps, 130 ps and 190 ps, respectively, which are unusually slow. At the same time, the solvation time-constants of the DMA3HF enol in the same set of solvents were measured as 100 ps, 150 ps and >300 ps, respectively. Thus, both the ESIPT and enol solvation time-constants in high n alcohols increase monotonically with the alkyl chain-length of the solvent, although the increase is not strictly proportional. It appears that the H-bonding capacity of the solvent is the single major factor influencing both processes, causing them to become closely correlated. Solvation causes a drastic change in the solvent molecular configuration around the excited enol, E*, inducing the breakage of DMA3HF...solvent inter-molecular H-bonding, which in turn promotes ESIPT. Following previously reported theoretical work on ESIPT, a qualitative description of the S1 potential energy surface can be formulated, where the involvement of solvent relaxation with the ESIPT process is explained. PMID- 26811026 TI - Diphenidine, a new psychoactive substance: metabolic fate elucidated with rat urine and human liver preparations and detectability in urine using GC-MS, LC-MSn , and LC-HR-MSn. AB - Diphenidine is a new psychoactive substance (NPS) sold as a 'legal high' since 2013. Case reports from Sweden and Japan demonstrate its current use and the necessity of applying analytical procedures in clinical and forensic toxicology. Therefore, the phase I and II metabolites of diphenidine should be identified and based on these results, the detectability using standard urine screening approaches (SUSAs) be elucidated. Urine samples were collected after administration of diphenidine to rats and analyzed using different sample workup procedures with gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-(high resolution)-mass spectrometry (LC-(HR)-MS). With the same approaches incubates of diphenidine with pooled human liver microsomes (pHLM) and cytosol (pHLC) were analyzed. According to the identified metabolites, the following biotransformation steps were proposed in rats: mono- and bis hydroxylation at different positions, partly followed by dehydrogenation, N,N-bis dealkylation, and combinations of them followed by glucuronidation and/or methylation of one of the bis-hydroxy-aryl groups. Mono- and bis-hydroxylation followed by dehydrogenation could also be detected in pHLM or pHLC. Cytochrome P450 (CYP) isozymes CYP1A2, CYP2B6, CYP2C9, and CYP3A4 were all capable of forming the three initial metabolites, namely hydroxy-aryl, hydroxy-piperidine, and bis-hydroxy-piperidine. In incubations with CYP2D6 hydroxy-aryl and hydroxy piperidine metabolites were detected. After application of a common users' dose, diphenidine metabolites could be detected in rat urine by the authors' GC-MS as well as LC-MSn SUSA. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26811028 TI - Oxaloacetate enhances neuronal cell bioenergetic fluxes and infrastructure. AB - We tested how the addition of oxaloacetate (OAA) to SH-SY5Y cells affected bioenergetic fluxes and infrastructure, and compared the effects of OAA to malate, pyruvate, and glucose deprivation. OAA displayed pro-glycolysis and pro respiration effects. OAA pro-glycolysis effects were not a consequence of decarboxylation to pyruvate because unlike OAA, pyruvate lowered the glycolysis flux. Malate did not alter glycolysis flux and reduced mitochondrial respiration. Glucose deprivation essentially eliminated glycolysis and increased mitochondrial respiration. OAA increased, while malate decreased, the cell NAD+/NADH ratio. Cytosolic malate dehydrogenase 1 protein increased with OAA treatment, but not with malate or glucose deprivation. Glucose deprivation increased protein levels of ATP citrate lyase, an enzyme which produces cytosolic OAA, whereas OAA altered neither ATP citrate lyase mRNA nor protein levels. OAA, but not glucose deprivation, increased cytochrome oxidase subunit 2, PGC1alpha, PGC1beta, and PGC1 related co-activator protein levels. OAA increased total and phosphorylated SIRT1 protein. We conclude that adding OAA to SH-SY5Y cells can support or enhance both glycolysis and respiration fluxes. These effects appear to depend, at least partly, on OAA causing a shift in the cell redox balance to a more oxidized state, that it is not a glycolysis pathway intermediate, and possibly its ability to act in an anaplerotic fashion. We examined how oxaloacetate (OAA) affects bioenergetic fluxes. To advance the understanding of how OAA mediates these changes, we compared the effects of OAA to malate, pyruvate, and glucose deprivation. We further examined how OAA affects levels of enzymes that facilitate its cytosolic metabolism, and found OAA increased the expression of malate dehydrogenase 1 (MDH1-cytosolic). We propose the following: OAA supports both glycolysis and respiration fluxes, shifts the cell redox balance toward a more oxidized state, and acts in an anaplerotic fashion. Abbreviations not defined in the text: MDH2, malate dehydrogenase 2 (mitochondrial). PMID- 26811029 TI - Cloning, Characterization, and Expression Analysis of MyD88 in Rana dybowskii. AB - The myeloid differentiation factor 88 (MyD88) is the most common adaptor protein in toll-like receptor (TLR) signaling pathways and plays an important role in the innate immune system. In this report, we conducted rapid amplification of complementary DNA (cDNA) ends (RACE), multiple sequence alignment, conserved domain search, phylogenetic tree construction, and quantitative real-time PCR to obtain and analyze the full-length cDNA sequence, the amino acid sequential structures, and the expression patterns of Rana dybowskii (Rd) MyD88. The full length cDNA of RdMyD88 is 1472 bp, with an open reading frame of 855 bp, encoding a protein of 285 amino acid residues. The RdMyD88 amino acid sequence contains a death domain (DD) and a Toll/interleukin-1 receptor (TIR) domain. RdMyD88 was calculated as a hydrophilic protein with predicted molecular mass and pI of 32.79 kDa and 6.00, respectively. Eighteen possible phosphorylation sites including eight serine residues, six tyrosine residues, and four threonine residues are predicted. Analysis of multiple sequence alignment and phylogenetic tree revealed that the predicted RdMyD88 protein is closest to its Xenopus counterparts. The PCR result showed that RdMyD88 is expressed in various tissues of R. dybowskii. Quantitative real-time PCR (qPCR) was used to examine the expression of RdMyD88 in the heart, liver, and kidney. After Rana grylio virus (RGV) exposure, the expression of RdMyD88 in the heart, liver, and kidney were significantly upregulated and reached peak levels at 48, 48, and 72 h post-infection (hpi), respectively. Meanwhile, in response to Aeromonas hydrophila (AH) infection, clear upregulation of RdMyD88 was observed in the heart, liver, and kidney and reached its peak at 48, 6, and 12 hpi, respectively. The highest levels of induction were found in the kidney after both RGV and AH infections. These findings indicate that RdMyD88 has a conserved structure and is probably an important component of the innate immunity in R. dybowskii. This report firstly characterized one adaptor molecule of the TLR signaling pathways in R. dybowskii, thereby providing reference for further researches on the amphibian innate immune system. PMID- 26811031 TI - Taste-masked tacrolimus-phospholipid nanodispersions: dissolution enhancement, taste masking and reduced gastric complications. AB - Through the integration of orthogonal central composite design and desirability function, this work aimed to explore the potential of quality by design in understanding the formulation of phospholipid-stabilized tacrolimus nanodispersions by microfluidization. The influence of homogenization pressure, microfluidization time and phospholipid concentration (X1-X3) on nanodispersion performance was studied. Nanodispersions were characterized by differential scanning calorimetric (DSC), X-ray diffractometer (XRD) and Fourier transform infrared (FTIR) analysis. Moreover, masking the unpalatable taste of tacrolimus and reducing the gastric complications were also evaluated. FTIR analysis indicated its interaction with phospholipid. DSC and XRD analysis revealed the amorphous transformation of tacrolimus within nanodispersions. The dissolution was enhanced by 35 folds and 15 folds after 0.5 and 2 h, respectively. Maximum tacrolimus content, yield, polydispersity index, percentages dissolved after 0.5 and 2 h of 99.3%, 100%, 0.864, 39.7% and 95.3%, respectively, with particle size of 160 nm were obtained at X1, X2 and X3 values of 20 000 psi, 6 min and 30%, respectively. The Euclidean distance values demonstrated masking the unpalatable taste and taste perversion to stimuli of tacrolimus in its optimized nanodispersion. Moreover, the ulcerative indices following raw tacrolimus and its optimized nanodispersion oral administration were 6.73 and 2.45, respectively, to indicate that nanodispersion was significantly less irritating to the gastric mucosa. PMID- 26811032 TI - Theme issue shoulder instability. PMID- 26811033 TI - Achilles tendon allograft for an irreparable massive rotator cuff tear with bony deficiency of the greater tuberosity. AB - Management of combined bony and tendinous deficiency of the posterosuperior rotator cuff represents a challenge in young patients. In this case report, a 44 year-old woman that presented an osteonecrosis of the greater tuberosity had a pseudoparalytic shoulder. She beneficiated from a fresh-frozen Achilles tendon allograft with calcaneal bone, which was used to reconstruct the rotator cuff and the concomitant bony defect. At 12-month follow-up, the patient was pain free and had complete range of motion, normal strength, a SANE score of 95 and radiographically the allograft was healed. An Achilles tendon allograft may therefore be a viable surgical option to reconstruct a combine posterosuperior rotator cuff tear and greater tuberosity bone defect. Level of evidence IV. PMID- 26811034 TI - Morphological evaluation of the sagittal plane femoral load-bearing surface in computer-simulated virtual total knee arthroplasty implantation at different flexion angles. AB - PURPOSE: To examine the effect of implantation of the femoral component of a total knee arthroplasty (TKA) system in 0 degrees , 3 degrees , and 6 degrees of flexion on the sagittal plane morphology of the femoral load-bearing surfaces. It was hypothesized that increasing the flexion angle would result in undersizing of the anterior surface without changing the flexion gap. METHODS: Computer simulation of a TKA using three-dimensional models of 10 healthy knees, matched to three different sized femoral components. Size discrepancy in the sagittal plane anterior, distal, and posterior joint surfaces between the native and prosthetic knees was calculated at 0 degrees , 3 degrees , and 6 degrees of flexion. RESULTS: The required component size varied with the angle of implantation: 0 degrees , size 3/size 4 (N = 7/3), 3 degrees , size 3 (N = 10); and 6 degrees , size 2/size 3 (N = 4/6). Component undersizing ranged between 4.4 6.3 mm at the anterior lateral surface, with a significant difference between 0 degrees and 6 degrees (p < 0.05), and 1.2-3.5 mm at the anterior medial surface. Component oversizing of the distal surface of the lateral condyle (2.9 mm) and undersizing of the medial surface of the posterior condyle (1.6-2.3 mm) were comparable at all three flexion angles of component implantation. CONCLUSIONS: Increasing the flexion angle of implantation increased the incidence of using a smaller size of femoral component without significant interference with the flexion gap. However, the effect of a smaller femoral component on undersizing of the anterior surface of the condyle and the impact on the extensor mechanism need to be considered. PMID- 26811035 TI - Kinematically aligned TKA can align knee joint line to horizontal. AB - PURPOSE: The joint line of the native knee is horizontal to the floor and perpendicular to the vertical weight-bearing axis of the patient in a bipedal stance. The purposes of this study were as follows: (1) to find out the distribution of the native joint line in a population of normal patients with normal knees; (2) to compare the native joint line orientation between patients receiving conventional mechanically aligned total knee arthroplasty (TKA), navigated mechanically aligned TKA, and kinematically aligned TKA; and (3) to determine which of the three TKA methods aligns the postoperative knee joint perpendicular to the weight-bearing axis of the limb in bipedal stance. METHODS: To determine the joint line orientation of a native knee, 50 full-length standing hip-to-ankle digital radiographs were obtained in 50 young, healthy individuals. The angle between knee joint line and the line parallel to the floor was measured and defined as joint line orientation angle (JLOA). JLOA was also measured prior to and after conventional mechanically aligned TKA (65 knees), mechanically aligned TKA using imageless navigation (65 knees), and kinematically aligned TKA (65 knees). The proportion of the knees similar to the native joint line was calculated for each group. RESULTS: The mean JLOA in healthy individuals was parallel to the floor (0.2 degrees +/- 1.1 degrees ). The pre-operative JLOA of all treatment groups slanted down to the lateral side. Postoperative JLOA slanted down to the lateral side in conventional mechanically aligned TKA (-3.3 degrees +/- 2.2 degrees ) and in navigation mechanically aligned TKA (-2.6 degrees +/- 1.8 degrees ), while it was horizontal to the floor in kinematically aligned TKA (0.6 degrees +/- 1.7 degrees ). Only 6.9 % of the conventional mechanically aligned TKA and 16.9 % of the navigation mechanically aligned TKA were within one SD of the mean JLOA of the native knee, while the proportion was significantly higher (50.8 %) in kinematically aligned TKA. The portion was statistically greater in mechanically aligned TKA group than the other two. CONCLUSION: Postoperative joint line orientation after kinematically aligned TKA was more similar to that of native knees than that of mechanically aligned TKA and horizontal to the floor. Kinematically aligned TKA can restore pre-arthritic knee joint line orientation, while mechanically aligned TKA is inefficient in achieving the purpose even if navigation TKA is employed. LEVEL OF EVIDENCE: III. PMID- 26811036 TI - A new method to diagnose discoid lateral menisci on radiographs. AB - PURPOSE: The aim of this study was to prove that it is feasible to diagnose discoid lateral meniscus in radiographs. Plain radiographic findings of discoid lateral menisci with matched controls were analysed and compared in a quantitative method. METHODS: Sixty consecutive patients (60 knees) who were diagnosed with discoid lateral meniscus (discoid group) by magnetic resonance imaging (MRI) were included. Another 60 age- and sex-matched controls with normal medial and lateral menisci on the basis of MRI findings were included as the control group. Each plain radiograph was evaluated from the anteroposterior view for the following variables: height of the fibular head (HFH), lateral joint space distance (LJSD), height of the lateral tibial spine (HLTS), obliquity of the lateral tibial plateau, obliquity of the lateral femoral condyle, distance from the lateral tibial spine to the lateral femoral condyle, height of the medial tibial spine, chordal distance of the femoral condyle (CDLF, CDMF), the HFH/LJSD, LJSD/HLTS and the CDLF/CDMF. RESULTS: A significant difference was found in the HFH, LJSD, HLTS, DLC, CDLF, HFH/LJSD and LJSD/HLTS between the two groups. The cut-off values of the HFH, LJSD, HLTS, DLC, CDLF, HFH/LJSD and LJSD/HLTS were 12.9 mm, 6.6 mm, 7.8 mm, 3.0 mm, 2.7 mm, 2.0 and 0.9, respectively. Among the cut-off values in diagnosing discoid lateral meniscus, the sensitivity, specificity and ROC curve area of LJSD/HLTS were as high as 73.6 %, 83.0 % and 0.8, respectively. The corresponding values of the HFH/LJSD were as high as 66.0 %, 86.8 % and 0.8. For the first two indicators, the results of the HFH/LJSD and LJSD/HLTS were higher than that of most other parameters. At the same time, the ROC curve area of the HFH/LJSD and LJSD/HLTS ranked highest among all the results. CONCLUSION: There were significant differences in the HFH, LJSD, HLTS, DLC, CDLF, HFH/LJSD and LJSD/HLTS, especially the HFH/LJSD and the LJSD/HLTS, between plain radiographic findings of discoid lateral meniscus patients and normal controls. The results of the HFH/LJSD and the LJSD/HLTS showed a positive impact on the diagnosis of discoid lateral meniscus in this research. These findings enable radiographs to screen for discoid lateral meniscus. LEVEL OF EVIDENCE: II. PMID- 26811039 TI - Introduction: Great Institutions in Cardiothoracic Surgery. PMID- 26811040 TI - The History of Heart Surgery at The Johns Hopkins Hospital. AB - Johns Hopkins has made many lasting contributions to cardiac surgery, including the discovery of heparin and the Blalock-Taussig Shunt, which represents the dawn of modern cardiac surgery. Equally important, Johns Hopkins has trained some of the world's leaders in academic cardiac surgery, and is committed to training the future leaders in our specialty. PMID- 26811038 TI - Frequency of virulence genes in mixed infections with Helicobacter pylori strains from a Mexican population. AB - BACKGROUND: Helicobacter pylori (H. pylori) is associated with gastroduodenal diseases. Virulence of clinical isolates is related to clinical outcome. Moreover, with microdiversity studies in clinical isolates from a single patient, but from a different origin (antrum or corpus), it is possible to demonstrate that there are simultaneous mixed infections. AIMS: To genotype H. pylori strains with multiplex PCR, according to their clinical virulence, and in this manner know the frequency of each genotype and relate it to clinical outcome in order to prevent the development of severe diseases. METHODS: A total of 210 patients with gastric alterations were studied. Virulence classification of H. pylori strains was carried out with multiplex PCR and 127 strains were identified as H. pylori by PCR (glmM and cagE). Genotype and clinical outcome were evaluated with the Fisher's exact test. In addition, RAPD-PCR was performed as a fingerprinting method to analyze mixed infections. RESULTS: The cagA, vacAs1, and vacAm1 genes were detected in all the clinical isolates. Strains were classified as: type i, 40.15% (51/127); type ii, 22.04% (28/127); and type iii, 28.4% (36/127), but two new different genotypes were also detected: (1) babA2+, cagA+, vacAs1+, 6.29% (8/127) and (2) babA2+, cagA-, vacAs2/m2+, 3.14% (4/127). The cagE gene was detected in type i strains. CONCLUSIONS: The Fisher's exact test did not support a significant association between clinical outcome and genotype. The main circulating genotypes in the Mexican population studied were: cagA+, vacAs1, and vacAm1. Multiplex PCR can be used as a screening test for H. pylori strains. Furthermore, the cagE gene is a good marker for identifying cag-PAI positive strains. PMID- 26811041 TI - Mayo Clinic: An Institutional History of General Thoracic Surgery. AB - The Mayo Clinic was started in Rochester, MN after a 1883 tornado disaster. The Mayo brothers, William and Charles began thoracic surgical procedures early in their career. Dr. Samuel Robinson is recognized as the first thoracic surgeon at Mayo. He was followed by Drs. Harrington and Claret who became famous surgeons. Many other notable surgeons have help to build the thoracic surgical practice into what is today a world renown center of excellence in thoracic surgery. PMID- 26811042 TI - The History of Duke Thoracic Surgery. AB - Since 1931, Duke Thoracic Surgery has been defined by excellence in patient care, research, and the education of leaders in surgery. In this work, the history, contributions, historic figures, and current structure of the program are reviewed. The program has cultivated a commitment to surgical investigation and training that persists to the present day. This commitment is manifest by the program's contributions to the field of cardiothoracic surgery, from the fundamental investigation of the coronary circulation and the development of the heat exchanger for myocardial preservation, to large-scale clinical trials in cardiac and thoracic surgery. PMID- 26811043 TI - History and Current Status of Cardiovascular Surgery at the University of Pennsylvania. AB - The cardiothoracic surgery program at the University of Pennsylvania has enjoyed a decades long tradition of leadership and contributions to the field. Consistent with its place as a robust contributor in a major academic medical center, its focus is on the tripartite mission of clinical care, research and education, including the provision of cutting edge care delivered to patients in a multidisciplinary fashion. Faculty members' pursuit of translational research facilitates the delivery of such exceptional treatment and provision of excellent care. This foundation is ideal for the training of the outstanding surgeons of tomorrow, as evidenced by a history of such contributions. PMID- 26811044 TI - Doctors of Thoracic Surgery: The Division of Thoracic Surgery at Toronto General Hospital. AB - The Division of Thoracic Surgery at Toronto General Hospital has a history of sustained excellence and commitment to patient care, research and innovation in Thoracic Surgery. Doctors of Thoracic Surgery (DOTSR) continues to be a leading thoracic division training surgeons who practice all over the world--impacting the treatment of patients with thoracic disease. Many leaders in our specialty worldwide have directly or indirectly trained in Toronto. At University Health Network and the University of Toronto, this academic division has continued to contribute and thrive in a highly supportive and productive research and clinical environment. PMID- 26811045 TI - Evolution of the Pediatric and Congenital Heart Surgery Service at Texas Children's Hospital: 1954-2015. AB - Heart surgery at Texas Children's Hospital can trace its origins to the beginning of pediatric and congenital heart surgery. Pioneers in the field--Dr. Denton Cooley and Dr. Dan McNamara--started the program in 1954 at a new pediatric hospital in Houston. Over the past 60 years, what is now Texas Children's Heart Center has grown become one of the leading pediatric heart institutions. PMID- 26811046 TI - One Hundred Years of History at Stanford University: Thoracic and Cardiovascular Surgery. AB - The history of thoracic and cardiovascular surgery at Stanford spans a century long period, beginning not long after the founding of Stanford University. Pioneering Stanford surgeons have made landmark discoveries and innovations in pulmonary, transplantation, thoracic aortic, mechanical circulatory support, minimally invasive, valvular, and congenital heart surgery. Fundamental research formed the foundation underlying these and many other advances. Educating and training the subsequent leaders of cardiothoracic surgery has throughout this century-long history constituted a mission of the highest merit. PMID- 26811047 TI - History of Cardiac Surgery at the Peter Bent Brigham and Brigham and Women's Hospital, Boston, Massachusetts. AB - The history of the Brigham dates from 1913, Harvey Cushing was the first chief of surgery and while at Hopkins did research on mitral stenosis, In 1913 he chose Elliot cutler to be a resident and in 1913 Cutler did the first successful valve operation in the world setting the tone of innovation and dedication to cardiac disease surgical treatment over the next century. There was large numbers of closed mitrals operations in 40s-60s. Bioprothetic valve implantation in the 70s mitral valve repair beginning in the 80s and continuing to the present and one of the first proponents of minimally invasive valve surgery starting in the 90s continuing to the present . PMID- 26811048 TI - The Thoracic Surgery Service at Memorial Sloan Kettering Cancer Center. AB - The development of the Thoracic Surgery Service at Memorial Sloan Kettering Cancer Center paralleled the emergence of Thoracic Surgery as a specialty, but with the unique focus on oncology and multidisciplinary cancer care characteristic of the institution. From the early post-war years treating lung cancer with new surgical techniques, through early definitive work in malignant mesothelioma, to today's translational research in cancer biology, the Thoracic Surgery Service continues to be an international leader in educating surgeons in thoracic surgical oncology, conducting clinical trials, and developing innovative therapies to treat thoracic cancers. PMID- 26811049 TI - Development of Congenital Cardiac Surgery in Toronto. AB - The development of congenital cardiac surgery required innovation by committed and talented individuals who integrated science, engineering and emerging medical knowledge while building a team of professionals dedicated to the care of patients. Life-long follow-up of these patients led to evolving management strategies to improve outcomes for neonates, infants, children and adults with congenital heart disease. PMID- 26811050 TI - Reduced secretion and altered proteolytic processing caused by missense mutations in progranulin. AB - Progranulin (GRN) is a secreted growth factor involved in various cellular functions, and loss-of-function mutations are a major cause of frontotemporal lobar degeneration (FTLD) with TDP-43 positive pathology. Most FTLD-related GRN mutations are nonsense mutations resulting in reduced GRN expression. Nonsynonymous GRN missense mutations have been described as risk factor for neurodegenerative brain diseases, but their pathogenic nature remains largely elusive. We identified a double missense mutation in GRN leading to amino acid changes p.D33E and p.G35R in an FTLD patient from Turkish origin. Biochemical and cell biological analysis of the double-mutation together with 2 so-far uncharacterized GRN missense mutations (p.C105R and p.V514M) revealed a reduced secretion efficiency of the GRN p.D33E/p.G35R and p.C105R proteins. Furthermore, loss of the conserved cysteine residue affects protein folding and altered proteolytic processing by neutrophil elastase and proteinase 3. Our data indicate that the described variants may cause a loss-of-function, albeit to a lesser extent than GRN null mutations, and hence could be considered as low-penetrant risk factors for neurodegenerative diseases. PMID- 26811051 TI - The nuclear receptor REV-ERBalpha represses the transcription of growth/differentiation factor 10 and 15 genes in rat endometrium stromal cells. AB - Cellular oscillators in the uterus play critical roles in the gestation processes of mammals through entraining of the clock proteins to numerous downstream genes, including growth/differentiation factor (Gdf)10 and Gdf15. The expression of Gdf10 and Gdf15 is significantly increased in the uterus during decidualization, but the mechanism underlying the regulation of Gdf gene expression in the uterus is poorly understood. Here, we focused on the function of the cellular oscillators in the expression of Gdf family by using uterine endometrial stromal cells (UESCs) isolated from pregnant Per2-dLuc transgenic rats. A significant decline of Per2-dLuc bioluminescence activity was induced in in vitro decidualized UESCs, and concomitantly the expression of canonical clock genes was downregulated. Conversely, the expression of Gdf10 and Gdf15 of the Gdf was upregulated. In UESCs transfected with Bmal1-specific siRNA, in which Rev erbalpha expression was downregulated, Gdf10 and Gdf15 were upregulated. However, Gdf5, Gdf7, and Gdf11 were not significantly affected by Bmal1 silencing. The expression of Gdf10 and Gdf15 was enhanced after treatment with a REV-ERBalpha antagonist in the presence or absence of progesterone. Chromatin immunoprecipitation-PCR analysis revealed the inhibitory effect of REV-ERBalpha on the expression of Gdf10 and Gdf15 in UESCs by recognizing their gene promoters. Collectively, our findings indicate that the attenuation of REV ERBalpha leads to an upregulation of Gdf10 and Gdf15 in decidual cells, in which cellular oscillators are impaired. Our results provide novel evidence regarding the functions of cellular oscillators regulating the expression of downstream genes during the differentiation of UESCs. PMID- 26811052 TI - Mechanisms responsible for postmenopausal hypertension in a rat model: Roles of the renal sympathetic nervous system and the renin-angiotensin system. AB - Hypertension in postmenopausal women is less well controlled than in age-matched men. The aging female SHR is a model of postmenopausal hypertension that is mediated in part by activation of the renin-angiotensin system (RAS) and by the renal sympathetic nervous system. In this study, the hypothesis was tested that renal denervation would lower the blood pressure in old female SHR and would attenuate the antihypertensive effects of AT1 receptor antagonism. Retired breeder female SHR were subjected to right uninephrectomy (UNX) and left renal denervation (RD) or UNX and sham, and 2 weeks later, baseline mean arterial pressure (MAP; radiotelemetry) was measured for 4 days, and then rats were treated with angiotensin (AT1) receptor antagonist, losartan (40 mg/kg/day po) for 6 days. Renal denervation reduced MAP in old females compared to sham (172 +/ 6 vs. 193 +/- 6 mm Hg; P < 0.05). Losartan reduced MAP in both sham and RD rats similarly (numerically and by percentage) (142 +/- 10 vs. 161 +/- 6 mm Hg; P < 0.05 vs. RD, P < 0.05 vs. baseline). However, female SHR rats remained significantly hypertensive despite both pharmacological intervention and RD. The data suggest that both the renal sympathetic nervous system and the RAS have independent effects to control the blood pressure in old female SHR. Since the denervated rats treated with losartan remained hypertensive, the data also suggest that other mechanisms than the RAS and renal sympathetic nervous system contribute to the hypertension in old female SHR. The data also suggest that multiple mechanisms may mediate the elevated blood pressure in postmenopausal women. PMID- 26811053 TI - Chronic hypoxia does not cause wall thickening of intra-acinar pulmonary supernumerary arteries. AB - Chronic exposure to hypoxia causes pulmonary hypertension and pulmonary arterial remodeling. Although the exact mechanisms of this remodeling are unclear, there is evidence that it is dependent on hemodynamic stress, rather than on hypoxia alone. Pulmonary supernumerary arteries experience low hemodynamic stress as a consequence of reduced perfusion due to 90 degrees branching angles, small diameters, and "valve-like" structures at their orifices. We investigated whether or not intra-acinar supernumerary arteries undergo structural remodeling during the moderate pulmonary hypertension induced by chronic hypoxia. Rats were exposed to either normoxia or hypoxia for 6 weeks. The chronically hypoxic rats developed pulmonary hypertension. For both groups, pulmonary arteries were selectively filled with barium-gelatin mixture, and the wall thickness of intra-acinar pulmonary arteries was measured in histological samples. Only thin-walled arteries were observed in normoxic lungs. In hypertensive lungs, we found both thin- and thick-walled pulmonary arteries with similar diameters. Disproportionate degrees of arterial wall thickening between parent and daughter branches were observed with supernumerary branching patterns. While parent arteries developed significant wall thickening, their supernumerary branches did not. Thus, chronic hypoxia-induced pulmonary hypertension did not cause wall thickening of intra-acinar pulmonary supernumerary arteries. These findings are consistent with the idea that hemodynamic stress, rather than hypoxia alone, is the cause of structural remodeling during chronic exposure to hypoxia. PMID- 26811054 TI - Altered physiological functions and ion currents in atrial fibroblasts from patients with chronic atrial fibrillation. AB - The contribution of human atrial fibroblasts to cardiac physiology and pathophysiology is poorly understood. Fibroblasts may contribute to arrhythmogenesis through fibrosis, or by directly altering electrical activity in cardiomyocytes. The objective of our study was to uncover phenotypic differences between cells from patients in sinus rhythm (SR) and chronic atrial fibrillation (AF), with special emphasis on electrophysiological properties. We isolated fibroblasts from human right atrial tissue for patch-clamp experiments, proliferation, migration, and differentiation assays, and gene expression profiling. In culture, proliferation and migration of AF fibroblasts were strongly impaired but differentiation into myofibroblasts was increased. This was associated with a higher number of AF fibroblasts expressing functional Nav1.5 channels. Strikingly Na(+) currents were considerably larger in AF cells. Blocking Na(+) channels in culture with tetrodotoxin did not affect proliferation, migration, or differentiation in neither SR nor AF cells. While freshly isolated fibroblasts showed mostly weak rectifier currents, fibroblasts in culture developed outward rectifier K(+) currents of similar amplitude between the SR and AF groups. Adding the K(+) channel blockers tetraethylammonium and 4 aminopyridin in culture reduced current amplitude and inhibited proliferation in the SR group only. Analysis of gene expression revealed significant differences between SR and AF in genes encoding for ion channels, collagen, growth factors, connexins, and cadherins. In conclusion, this study shows that under AF conditions atrial fibroblasts undergo phenotypic changes that are revealed in culture. Future experiments should be performed in situ to understand the nature of those changes and whether they affect cardiac electrical activity. PMID- 26811055 TI - Changes in corticospinal drive to spinal motoneurones following tablet-based practice of manual dexterity. AB - The use of touch screens, which require a high level of manual dexterity, has exploded since the development of smartphone and tablet technology. Manual dexterity relies on effective corticospinal control of finger muscles, and we therefore hypothesized that corticospinal drive to finger muscles can be optimized by tablet-based motor practice. To investigate this, sixteen able bodied females practiced a tablet-based game (3 * 10 min) with their nondominant hand requiring incrementally fast and precise pinching movements involving the thumb and index fingers. The study was designed as a semirandomized crossover study where the participants attended one practice- and one control session. Before and after each session electrophysiological recordings were obtained during three blocks of 50 precision pinch movements in a standardized setup resembling the practiced task. Data recorded during movements included electroencephalographic (EEG) activity from primary motor cortex and electromyographic (EMG) activity from first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles. Changes in the corticospinal drive were evaluated from coupling in the frequency domain (coherence) between EEG-EMG and EMG-EMG activity. Following motor practice performance improved significantly and a significant increase in EEG-EMGAPB and EMGAPB-EMGFDI coherence in the beta band (15-30 Hz) was observed. No changes were observed after the control session. Our results show that tablet-based motor practice is associated with changes in the common corticospinal drive to spinal motoneurons involved in manual dexterity. Tablet-based motor practice may be a motivating training tool for stroke patients who struggle with loss of dexterity. PMID- 26811059 TI - Increased protein degradation as well as lactate and malate dehydrogenase activity in sterile and infected walled-off pancreatic necrosis. PMID- 26811056 TI - Cardiorespiratory control and cytokine profile in response to heat stress, hypoxia, and lipopolysaccharide (LPS) exposure during early neonatal period. AB - Sudden infant death syndrome (SIDS) is one of the most common causes of postneonatal infant mortality in the developed world. An insufficient cardiorespiratory response to multiple environmental stressors (such as prone sleeping positioning, overwrapping, and infection), during a critical period of development in a vulnerable infant, may result in SIDS. However, the effect of multiple risk factors on cardiorespiratory responses has rarely been tested experimentally. Therefore, this study aimed to quantify the independent and possible interactive effects of infection, hyperthermia, and hypoxia on cardiorespiratory control in rats during the neonatal period. We hypothesized that lipopolysaccharide (LPS) administration will negatively impact cardiorespiratory responses to increased ambient temperature and hypoxia in neonatal rats. Sprague-Dawley neonatal rat pups were studied at postnatal day 6 8. Rats were examined at an ambient temperature of 33 degrees C or 38 degrees C. Within each group, rats were allocated to control, saline, or LPS (200 MUg/kg) treatments. Cardiorespiratory and thermal responses were recorded and analyzed before, during, and after a hypoxic exposure (10% O2). Serum samples were taken at the end of each experiment to measure cytokine concentrations. LPS significantly increased cytokine concentrations (such as TNFalpha, IL-1beta, MCP 1, and IL-10) compared to control. Our results do not support a three-way interaction between experimental factors on cardiorespiratory control. However, independently, heat stress decreased minute ventilation during normoxia and increased the hypoxic ventilatory response. Furthermore, LPS decreased hypoxia induced tachycardia. Herein, we provide an extensive serum cytokine profile under various experimental conditions and new evidence that neonatal cardiorespiratory responses are adversely affected by dual interactions of environmental stress factors. PMID- 26811058 TI - RGS2 squelches vascular Gi/o and Gq signaling to modulate myogenic tone and promote uterine blood flow. AB - Uterine artery blood flow (UABF) is critical to maintaining uterine perfusion in nonpregnant states and for uteroplacental delivery of nutrients and oxygen to the fetus during pregnancy. Impaired UABF is implicated in infertility and several pregnancy complications including fetal growth restriction, small for gestational age, and preeclampsia. The etiology of abnormal UABF is not known. Here, we determined whether deficiency or loss of RGS2, a GTPase-activating protein for Gq/11 and Gi/o class G proteins, affects UABF in nonpregnant mice. We used Doppler ultrasonography to assess UABF in wild type (WT), Rgs2 heterozygous (Rgs2+/-), and homozygous knockout (Rgs2-/-) mice. Video microscopy was used for ex vivo examination of uterine artery myogenic tone and fura-2 imaging for in vitro assessment of internal stores Ca(2+) release. We found that baseline UABF velocity was markedly decreased while impedance measured as resistive index (WT = 0.58 +/- 0.04 vs. Rgs2-/- = 0.71 +/- 0.03, P < 0.01) and pulsatile index (WT = 0.90 +/- 0.06 vs. Rgs2-/- = 1.25 +/- 0.11, P < 0.01) was increased in Rgs2-/- mice. Uterine artery tone was augmented in Rgs2+/- and Rgs2-/- mice, which was normalized to WT levels following Gi/o and Gq inactivation. Conversely, blockade of ryanodine receptors increased WT myogenic tone to RGS2 mutant levels. The data together indicate that RGS2 deficiency decreases UABF by increasing myogenic tone at least partly through prolonged G protein activation. Mutations that decrease vascular RGS2 expression may be a predisposition to decreased uterine blood flow. Targeting G protein signaling therefore might improve uterine and uteroplacental underperfusion disorders. PMID- 26811057 TI - Modulation of heart rate by temporally patterned vagus nerve stimulation in the anesthetized dog. AB - Despite current knowledge of the myriad physiological effects of vagus nerve stimulation (VNS) in various mammalian species (including humans), the impact of varying stimulation parameters on nerve recruitment and physiological responses is not well understood. We investigated nerve recruitment, cardiovascular responses, and skeletal muscle responses to different temporal patterns of VNS across 39 combinations of stimulation amplitude, frequency, and number of pulses per burst. Anesthetized dogs were implanted with stimulating and recording cuff electrodes around the cervical vagus nerve, whereas laryngeal electromyogram (EMG) and heart rate were recorded. In seven of eight dogs, VNS-evoked bradycardia (defined as >=10% decrease in heart rate) was achieved by applying stimuli at amplitudes equal to or greater than the threshold for activating slow B-fibers. Temporally patterned VNS (minimum 5 pulses per burst) was sufficient to elicit bradycardia while reducing the concomitant activation of laryngeal muscles by more than 50%. Temporal patterns of VNS can be used to modulate heart rate while minimizing laryngeal motor fiber activation, and this is a novel approach to reduce the side effects produced by VNS. PMID- 26811060 TI - Randomized, controlled trial comparing laryngeal mask versus endotracheal intubation during neonatal resuscitation---a secondary publication. AB - BACKGROUND: This study aimed to study the feasibility, efficacy and safety of using laryngeal mask (LM) ventilation compared with endotracheal intubation (ETI) during neonatal resuscitation. METHODS: Neonates with a heart rate below 60 beats per minute despite 30 s of face mask ventilation were assigned quasi-randomly (odd/even birth date) to LM (n = 36) or ETI (n = 32) ventilation. Differences in first attempt insertion success, insertion time, Apgar score, resuscitation outcome, and adverse effects were compared. RESULTS: There were no significant differences in first attempt at successful insertion (LM, 94.4 % vs. ETI, 90.6 %), insertion time (LM, 7.58 +/- 1.16 s vs. ETI, 7.89 +/- 1.52 s), Apgar score at 1 and 5 min, response time, ventilation time, successful resuscitation (LM, 86.1 % vs. ETI, 96.9 %), and adverse events (LM, n =3 vs. ETI, n =4) between groups. CONCLUSIONS: Laryngeal mask ventilation is an effective alternative to endotracheal intubation during resuscitation of depressed newborns who do not respond to face-mask ventilation. During an emergency, laryngeal mask ventilation may be a preferred technique for medical staff who are unable to acquire or maintain endotracheal intubation skills. TRIAL REGISTRATION: Current Controlled Trials ChiCTR-IOQ-15006488. Registered on 2 June 2015. PMID- 26811062 TI - Investigating the impact of passive external lower limb compression on central and peripheral hemodynamics during exercise. AB - PURPOSE: The objective of this study was to assess the effectiveness of graduated compression socks (GCS) on enhancing muscle blood flow and oxygenation during exercise and recovery in healthy subjects. METHODS: Twelve healthy volunteers completed a protocol involving baseline, exercise, and recovery periods with and without GCS. Each test was repeated twice to assess repeatability of the results. The applied sock pressure was measured prior to experimentation using a custom pressure sensing system, and modified as necessary using tensor bandages to control the applied load. During each of the experimental phases, blood velocity in the popliteal artery, calf muscle tissue oxygenation, muscle activity, heart rate, blood pressure, cardiac output, and applied pressure from the sock were measured. Popliteal artery diameter was measured during baseline and recovery periods. RESULTS: The GCS significantly reduced deoxyhemoglobin (HHb) in the leg during baseline (HHb, p = 0.001) and total blood volume and HHb in the leg during exercise (total hemoglobin, p = 0.01; HHb, p = 0.02). However, there were no differences in leg muscle blood flow velocity or any other variables with and without GCS at baseline, exercise, or recovery. Interestingly, it was found that the local applied sock pressure was very sensitive to the sock application process and, furthermore, the pressure varied considerably during exercise. CONCLUSIONS: No significant changes were observed in measures reflecting oxygen delivery for healthy subjects using GCS during exercise and recovery. Applied sock pressure was carefully controlled, thus eliminating the sock application process as a variable. PMID- 26811063 TI - How to determine protective immunity in the post-vaccine era. AB - The ability to determine an individual's susceptibility to infection relies heavily on the assay used, and the ability to correlate results of the assay to a clinical interpretation. Current rubella immunity screening methods identify total rubella IgG antibodies circulating in the serum, however both humoral and cell mediated immune responses have been shown to contribute to protection from infection. Therefore, antibody screening assays may under-estimate immunity in some populations. In fact, waning antibody titers over time in a large prenatal population were recently documented in North America, and the trend has been echoed in other countries that have achieved elimination through universal rubella vaccination. Despite decreasing antibody titers, the number of acute rubella cases has not increased in these populations, suggesting that the lower antibody levels may still be protective. Based on the changing epidemiology in universally vaccinated populations, it may be time to reassess the level of antibody that indicates immunity to rubella infection. PMID- 26811064 TI - Combination of the toll like receptor agonist and alpha-Galactosylceramide as an efficient adjuvant for cancer vaccine. AB - BACKGROUND: DNA vaccines have emerged as an attractive approach for the generation of cytotoxic T lymphocytes (CTL). In our previous study, we found That Toll like receptor (TLR) ligands are promising candidates for the development of novel adjuvants for DNA vaccine. To improve the efficacy of DNA vaccine directed against human papillomavirus (HPV) tumors, we evaluated whether co-administration of a TLR4 ligand, monophosphoryl lipid A (MPL), and Natural Killer T Cell Ligand alpha-Galactosylceramide(alpha-GalCer) adjuvants with DNA vaccine would influence the anti-tumor efficacy of DNA vaccinations. METHODS: We investigated the effectiveness of alpha-GalCer and MPL combination as an adjuvant with an HPV-16 E7 DNA vaccine to enhance antitumor immune responses. RESULTS: By using adjuvant combination for a DNA vaccine, we found that the levels of lymphocyte proliferation, CTL activity, IFN- gamma, IL-4 and IL-12 responses, and tumor protection against TC-1 cells were significantly increased compared to the DNA vaccine with individual adjuvants. In addition, inhibition of IL-18 signaling during vaccination decreased IFN-gamma responses and tumor protection, and that this inhibition suggested stimulatory role of IL-18 in adjuvant effects of alpha GalCer and MPL combination. CONCLUSION: The strong adjuvanticity associated with alpha-GalCer/MPL combination may to be an important tool in the development of novel and strong cancer immunotherapy. PMID- 26811067 TI - Chitosan nerve tube for primary repair of traumatic sensory nerve lesions of the hand without a gap: study protocol for a randomized controlled trial. AB - BACKGROUND: Complex peripheral nerve injuries of the hand include at least 300,000 cases per year in Europe. The standard treatment involves a microsurgical end-to-end suture of traumatic sensory nerve lesions of the hand without a gap. The objective of this study protocol is to evaluate whether the additional use of a chitosan nerve tube in primary repair of traumatic sensory nerve lesions of the hand without a gap has an effect on the recovery of sensitivity. METHODS/DESIGN: We planned a randomized double-blind controlled multicenter trial with a parallel group design in order to show superiority for the additional use of a chitosan nerve tube. This study will enroll 100 participants with traumatic sensory nerve lesions of the hand without a gap from three Trauma Care Centers. Participants will be randomized in a 1:1 ratio to primary microsurgical repair of the injured nerve with the additional use of a chitosan nerve tube or direct tension free microsurgical repair of the injured nerve alone. The static two-point discrimination of the injured finger after 6 months will be the primary outcome parameter. DISCUSSION: In the proposed study, the additional use of a chitosan nerve tube for a primary microsurgical repair of traumatic sensory nerve lesions of the hand without a gap will be evaluated in a prospective randomized double blind controlled multicenter trial for the first time to create the highest possible evidence for the procedure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02372669 . Protocol Registration Receipt on 27 February 2015. PMID- 26811070 TI - Hypoelectronic isomeric diiridaboranes [(Cp*Ir)2B6H6]: the "Rule-Breakers"(Cp* = eta(5)-C5Me5). AB - In an effort to synthesize supraicosahedral iridaboranes, pyrolysis of [Cp*IrCl2]2 with excess [BH3.] was carried out, and this synthesis afforded the isomeric iridaborane [(Cp*Ir)2B6H6] clusters 1 and 2. The geometry of 1 was determined to be dodecahedral, i.e., similar to that of [B8H8](2-), whereas 2 was found to exhibit a cluster shape that can be derived from a nine-vertex tricapped trigonal prism by removing one of the capped vertices. The calculation of a large HOMO-LUMO gap further rationalized the isocloso structures for these isomers. PMID- 26811068 TI - Myeloid dendritic cells are decreased in peripheral blood of Alzheimer's disease patients in association with disease progression and severity of depressive symptoms. AB - BACKGROUND: Dendritic cells (DCs) are major orchestrators of immune responses and inflammation. They are migratory cells, which may play a role in Alzheimer's disease (AD), as suggested by prior in vitro studies. With the intent to investigate the clinical relevance of DC modifications in vivo, the present study was aimed to evaluate the levels of blood DCs in AD patients, in relation to the progression of the disease, the severity of its symptoms, and the treatment with acetylcholinesterase inhibitors (AChEIs), a class of drugs used to improve cognitive functioning in people with dementia. METHODS: The two main subpopulations of immature blood DCs, namely myeloid (mDCs) and plasmacytoid (pDCs) cells, were evaluated by flow cytometry analysis in 106 AD patients, in comparison with the same cells from 65 individuals with mild cognitive impairment (MCI) and 73 healthy control subjects (HC). The relationship between blood DC levels and symptom severity was also assessed in AD patients, and their blood DC frequency was considered both in the absence or presence of treatment with AChEIs. RESULTS: A significant depletion in blood mDCs was observed in AD patients, as compared to HC and MCI subjects. At variance, pDC levels were comparable among the three groups of subjects. The mDC decrease was evident only after the emergence of AD clinical symptoms, as confirmed by the follow-up analysis of a subgroup of MCI subjects who exhibited a significant decline in mDCs after their conversion to AD. Notably, the mDC decline was inversely correlated in AD patients with the frequency and severity of depressive symptoms. Eventually, the mDC depletion was not observable in patients treated with AChEIs. CONCLUSIONS: Our results provide the first evidence that blood mDC levels are dysregulated in AD. This phenomenon appears mainly linked to AD progression, associated with stronger severity of AD-related symptoms, and influenced by AChEI treatment. Taken all together, these data suggest that blood mDCs may serve as a cell source to test disease-induced and treatment-related changes and support the innovative notion that DCs play a role in AD, as ultimate evidence of the immune system participation in disease progression. PMID- 26811069 TI - Ilizarov distraction osteogenesis over the preexisting nail for treatment of nonunited femurs with significant shortening. AB - PURPOSE: Nonunion of the femur with significant shortening with retained intramedullary nail (IMN) is a challenging orthopedic problem. We investigated whether the application of Ilizarov distraction osteogenesis over the preexisting nail can simultaneously achieve union and correct shortening. METHODS: Thirteen patients with femoral diaphyseal nonunion associated with significant shortening with retained IMN were retrospectively reviewed. All patients were treated by distraction osteogenesis using a circular external fixator over the preexisting nail. The fixator was used to compress or distract the nonunion site and to gradually distract a separate osteotomy to restore limb length. The osteotomy was done percutaneously using the Gigli saw with the nail in situ. The applied surgical technique was bifocal compression distraction in 11 cases, bifocal distraction in one case, and monofocal distraction in one case. RESULTS: Bone healing was achieved in 11 cases (84.6 %) at both the nonunion and the lengthening sites. The mean length gained was 4 cm (range, 3-6 cm). The mean time to fracture union was 4.9 months (range, 4-6 months). The mean knee flexion improved from 86.5 degrees (range, 40 degrees -135 degrees ) preoperatively to 109.6 degrees (range, 60 degrees -125 degrees ) at final follow-up (p < 0.05). The mean limb-length discrepancy improved from 4.7 cm (range, 3-7.5) preoperatively to 0.7 cm (range, 0-3) at final follow-up (p < 0.001). Ten out of 13 patients had a total of 14 complications, with a mean of 1.1 complications per patient. CONCLUSIONS: Distraction osteogenesis over the preexisting nail can be a good alternative to treat difficult femoral diaphyseal nonunions associated with significant shortening. PMID- 26811071 TI - The importance of shaving the zygomatic process during reduction malarplasty. AB - Reduction malarplasty surgery has become increasingly popular in recent years, especially in many East Asian countries. This is, in part, because many Asians consider a small, smooth, and feminine face to be more attractive and aesthetically desirable. Among the various reduction malarplasty methods, the L shaped osteotomy technique, through intraoral and sideburn incisions, is now one of the most frequently performed surgical techniques. During the surgical procedure, it is important to shave the zygomatic process of the temporal bone through the sideburn incision. By carrying out this simple adjunctive procedure, several remarkable results can be achieved. The facial width is reduced, especially in those patients with protrusion of the posterior portion of the arch. The outward curvature of the zygomatic arch is changed to point inward. And finally, the bony step that originates from the medial repositioning of the zygomatic arch is reduced, resulting in decreased palpability. PMID- 26811072 TI - Mutational analysis of PI3K/AKT and RAS/RAF pathway activation in malignant salivary gland tumours with a new mutation of PIK3CA. AB - The phosphoinositide 3-kinase (PIK3)/v-akt murine thymoma (AKT) oncogene pathway and the RAS/RAF pathway are involved in regulating the signalling of multiple biological processes, including apoptosis, metabolism, cell proliferation, and cell growth. Mutations in the genes within these pathways are frequently found in several tumours. The aim of this study was to investigate the frequency of mutations in the PIK3CA, BRAF, and KRAS genes in cases of malignant salivary gland tumours. Mutational analysis of the PIK3CA, KRAS, and BRAF genes was performed by direct sequencing of material from 21 patients with malignant salivary gland tumours who underwent surgery between 1992 and 2001. No mutations were found in the KRAS exon 2, BRAF exon 15, or PIK3CA exon 9 genes. However, an unpublished mutation of the PIK3CA gene in exon 20 (W1051 stop mutation) was found in one case of adenocarcinoma NOS. The impact of this mutation on the biological behaviour of the tumour has yet to be explored, however the patient with adenocarcinoma NOS harbouring this mutation has survived for over 20 years following surgery despite a high stage at presentation. Further studies with more homogeneous patient cohorts are needed to address whether this mutation reflects a different clinical presentation and may benefit from targeted treatment strategies. PMID- 26811073 TI - Mass Detection in Mammographic Images Using Wavelet Processing and Adaptive Threshold Technique. AB - Detection of mass in mammogram for early diagnosis of breast cancer is a significant assignment in the reduction of the mortality rate. However, in some cases, screening of mass is difficult task for radiologist, due to variation in contrast, fuzzy edges and noisy mammograms. Masses and micro-calcifications are the distinctive signs for diagnosis of breast cancer. This paper presents, a method for mass enhancement using piecewise linear operator in combination with wavelet processing from mammographic images. The method includes, artifact suppression and pectoral muscle removal based on morphological operations. Finally, mass segmentation for detection using adaptive threshold technique is carried out to separate the mass from background. The proposed method has been tested on 130 (45 + 85) images with 90.9 and 91 % True Positive Fraction (TPF) at 2.35 and 2.1 average False Positive Per Image(FP/I) from two different databases, namely Mammographic Image Analysis Society (MIAS) and Digital Database for Screening Mammography (DDSM). The obtained results show that, the proposed technique gives improved diagnosis in the early breast cancer detection. PMID- 26811074 TI - Image De-Identification Methods for Clinical Research in the XDS Environment. AB - To investigate possible de-identification methodologies within the Cross Enterprise Document Sharing for imaging (XDS-I) environment in order to provide strengthened support for image data exchange as part of clinical research projects. De-identification, using anonymization or pseudonymization, is the most common method to perform information removal within DICOM data. However, it is not a standard part of the XDS-I profiles. Different methodologies were observed to define how and where de-identification should take place within an XDS environment used for scientific research. De-identification service can be placed in three locations within the XDS-I framework: 1) within the Document Source, 2) between the Document Source and Document Consumer, and 3) within the Document Consumer. First method has a potential advantage with respect to the exposure of the images to outside systems but has drawbacks with respect to additional hardware and configuration requirements. Second and third method have big concern in exposing original documents with all identifiable data being intact after leaving the Document Source. De-identification within the Document Source has more advantages compared to the other methods. On the contrary, it is less recommended to perform de-identification within the Document Consumer since it has the highest risk of the exposure of patients identity due to the fact that images are exposed without de-identification during the transfers. PMID- 26811075 TI - Corneal thermal damage threshold dependence on the exposure duration for near infrared laser radiation at 1319 nm. PMID- 26811076 TI - Ablation characteristics of quantum square pulse mode dental erbium laser. PMID- 26811077 TI - Photothermal enhancement of chemotherapy mediated by gold-silica nanoshell-loaded macrophages: in vitro squamous cell carcinoma study. PMID- 26811079 TI - Progressive internal landmark registration for surgical navigation in laparoscopic gastrectomy for gastric cancer. AB - PURPOSE: A surgical navigation system supports the comprehension of anatomical information during surgery. Patient-to-image registration is the alignment process between CT volume and patient coordinate systems. Achieving accurate registration in the surgical navigation of laparoscopic surgery is very challenging due to soft tissue deformation. This paper presents a new patient-to image registration method based on internal anatomical landmarks for improving registration accuracy in the surgical navigation of laparoscopic gastrectomy for gastric cancer. METHODS: Our proposed registration method progressively utilizes internal anatomical landmarks. In laparoscopic gastrectomy for gastric cancer, the surgeon cuts the blood vessels around the stomach. The positions of the cut vessels are sequentially used as fiducials for registration during surgery. The proposed method uses a weighted point-based registration method for computing the transformation matrix using the fiducials both on the body surface and on the blood vessels. When a blood vessel is cut during surgery, the proposed progressive registration method measures the cut vessel's position and computes a transformation matrix by adding the cut vessel as a fiducial. RESULTS: We applied our proposed progressive registration method using the positional information of the blood vessels acquired during laparoscopic gastrectomy in 20 cases. We evaluated it using target registration error in four blood vessels. The average target registration error in the four blood vessels was 12.6 mm and ranged from 2.1 to 32.9 mm. CONCLUSION: Since the proposed progressive registration can reduce registration error, our proposed method is very useful for the surgical navigation of laparoscopic gastrectomy. Our proposed progressive registration method might increase the accuracy of surgical navigation in laparoscopic gastrectomy. PMID- 26811078 TI - Automatic path proposal computation for CT-guided percutaneous liver biopsy. AB - PURPOSE: To evaluate feasibility of automatic software-based path proposals for CT-guided percutaneous biopsies. METHODS: Thirty-three patients (60 [Formula: see text] 12 years) referred for CT-guided biopsy of focal liver lesions were consecutively included. Pre-interventional CT and dedicated software (FraunhoferMeVis Pathfinder) were used for (semi)automatic segmentation of relevant structures. The software subsequently generated three path proposals in downward quality for CT-guided biopsy. Proposed needle paths were compared with consensus proposal of two experts (comparable, less suitable, not feasible). In case of comparable results, equivalent approach to software-based path proposal was used. Quality of segmentation process was evaluated (Likert scale, 1 [Formula: see text] best, 6 [Formula: see text] worst), and time for processing was registered. RESULTS: All biopsies were performed successfully without complications. In 91 % one of the three automatic path proposals was rated comparable to experts' proposal. None of the first proposals was rated not feasible, and 76 % were rated comparable to the experts' proposal. 7 % automatic path proposals were rated not feasible, all being second choice ([Formula: see text]) or third choice ([Formula: see text]). In 79 %, segmentation at least was good. Average total time for establishing automatic path proposal was 42 [Formula: see text] 9 s. CONCLUSION: Automatic software-based path proposal for CT-guided liver biopsies in the majority provides path proposals that are easy to establish and comparable to experts' insertion trajectories. PMID- 26811080 TI - Precise 3D/2D calibration between a RGB-D sensor and a C-arm fluoroscope. AB - PURPOSE: Calibration and registration are the first steps for augmented reality and mixed reality applications. In the medical field, the calibration between an RGB-D camera and a C-arm fluoroscope is a new topic which introduces challenges. METHOD: A convenient and efficient calibration phantom is designed by combining the traditional calibration object of X-ray images with a checkerboard plane. After the localization of the 2D marker points in the X-ray images and the corresponding 3D points from the RGB-D images, we calculate the projection matrix from the RGB-D sensor coordinates to the X-ray, instead of estimating the extrinsic and intrinsic parameters simultaneously. VALIDATION: In order to evaluate the effect of every step of our calibration process, we performed five experiments by combining different steps leading to the calibration. We also compared our calibration method to Tsai's method to evaluate the advancement of our solution. At last, we simulated the process of estimating the rotation movement of the RGB-D camera using MATLAB and demonstrate that calculating the projection matrix can reduce the angle error of the rotation. RESULTS: A RMS reprojection error of 0.5 mm is achieved using our calibration method which is promising for surgical applications. Our calibration method is more accurate when compared to Tsai's method. Lastly, the simulation result shows that using a projection matrix has a lower error than using intrinsic and extrinsic parameters in the rotation estimation. CONCLUSIONS: We designed and evaluated a 3D/2D calibration method for the combination of a RGB-D camera and a C-arm fluoroscope. PMID- 26811081 TI - Comparing position and orientation accuracy of different electromagnetic sensors for tracking during interventions. AB - PURPOSE: To compare the position and orientation accuracy between using one 6 degree of freedom (DOF) electromagnetic (EM) sensor, or the position information of three 5DOF sensors within the scope of tumor tracking. METHODS: The position accuracy of Northern Digital Inc Aurora 5DOF and 6DOF sensors was determined for a table-top field generator (TTFG) up to a distance of 52 cm. For each sensor 716 positions were measured for 10 s at 15 Hz. Orientation accuracy was determined for each of the orthogonal axis at the TTFG distances of 17, 27, 37 and 47 cm. For the 6DOF sensors, orientation was determined for sensors in-line with the orientation axis, and perpendicular. 5DOF orientation accuracy was determined for a theoretical 4 cm tumor. An optical tracking system was used as reference. RESULTS: Position RMSE and jitter were comparable between the sensors and increasing with distance. Jitter was within 0.1 cm SD within 45 cm distance to the TTFG. Position RMSE was approximately 0.1 cm up to 32 cm distance, increasing to 0.4 cm at 52 cm distance. Orientation accuracy of the 6DOF sensor was within 1[Formula: see text], except when the sensor was in-line with the rotation axis perpendicular to the TTFG plane (4[Formula: see text] errors at 47 cm). Orientation accuracy using 5DOF positions was within 1[Formula: see text] up to 37 cm and 2[Formula: see text] at 47 cm. CONCLUSIONS: The position and orientation accuracy of a 6DOF sensor was comparable with a sensor configuration consisting of three 5DOF sensors. To achieve tracking accuracy within 1 mm and 1[Formula: see text], the distance to the TTFG should be limited to approximately 30 cm. PMID- 26811084 TI - Facial blushing: relevance of psychiatric consultation prior to surgery. PMID- 26811082 TI - Assessment of image features for vessel wall segmentation in intravascular ultrasound images. AB - BACKGROUND: Intravascular ultrasound (IVUS) provides axial greyscale images, allowing the assessment of the vessel wall and the surrounding tissues. Several studies have described automatic segmentation of the luminal boundary and the media-adventitia interface by means of different image features. PURPOSE: The aim of the present study is to evaluate the capability of some of the most relevant state-of-the-art image features for segmenting IVUS images. The study is focused on Volcano 20 MHz frames not containing plaque or containing fibrotic plaques, and, in principle, it could not be applied to frames containing shadows, calcified plaques, bifurcations and side vessels. METHODS: Several image filters, textural descriptors, edge detectors, noise and spatial measures were taken into account. The assessment is based on classification techniques previously used for IVUS segmentation, assigning to each pixel a continuous likelihood value obtained using support vector machines (SVMs). To retrieve relevant features, sequential feature selection was performed guided by the area under the precision-recall curve (AUC-PR). RESULTS: Subsets of relevant image features for lumen, plaque and surrounding tissues characterization were obtained, and SVMs trained with these features were able to accurately identify those regions. The experimental results were evaluated with respect to ground truth segmentations from a publicly available dataset, reaching values of AUC-PR up to 0.97 and Jaccard index close to 0.85. CONCLUSION: Noise-reduction filters and Haralick's textural features denoted their relevance to identify lumen and background. Laws' textural features, local binary patterns, Gabor filters and edge detectors had less relevance in the selection process. PMID- 26811083 TI - Radiotherapy volume delineation using dynamic [18F]-FDG PET/CT imaging in patients with oropharyngeal cancer: a pilot study. AB - PURPOSE: Delineation of gross tumour volume in 3D is a critical step in the radiotherapy (RT) treatment planning for oropharyngeal cancer (OPC). Static [18F] FDG PET/CT imaging has been suggested as a method to improve the reproducibility of tumour delineation, but it suffers from low specificity. We undertook this pilot study in which dynamic features in time-activity curves (TACs) of [18F]-FDG PET/CT images were applied to help the discrimination of tumour from inflammation and adjacent normal tissue. METHODS: Five patients with OPC underwent dynamic [18F]-FDG PET/CT imaging in treatment position. Voxel-by-voxel analysis was performed to evaluate seven dynamic features developed with the knowledge of differences in glucose metabolism in different tissue types and visual inspection of TACs. The Gaussian mixture model and K-means algorithms were used to evaluate the performance of the dynamic features in discriminating tumour voxels compared to the performance of standardized uptake values obtained from static imaging. RESULTS: Some dynamic features showed a trend towards discrimination of different metabolic areas but lack of consistency means that clinical application is not recommended based on these results alone. CONCLUSIONS: Impact of inflammatory tissue remains a problem for volume delineation in RT of OPC, but a simple dynamic imaging protocol proved practicable and enabled simple data analysis techniques that show promise for complementing the information in static uptake values. PMID- 26811085 TI - Skin vasomotor hemiparesis followed by overactivity: characteristic thermography findings in a patient with Horner syndrome due to spinal cord infarction. AB - We present a 21-year-old female with Horner syndrome due to spinal cord infarction. In this patient, infrared thermography revealed a hemibody skin temperature increase followed by excessive focal decreases, indicating skin vasomotor hemiparesis and overactivity. PMID- 26811087 TI - The Future Ecology of Care. PMID- 26811086 TI - Lignin biosynthesis in wheat (Triticum aestivum L.): its response to waterlogging and association with hormonal levels. AB - BACKGROUND: Lignin is an important structural component of plant cell wall that confers mechanical strength and tolerance against biotic and abiotic stressors; however it affects the use of biomass such as wheat straw for some industrial applications such as biofuel production. Genetic alteration of lignin quantity and quality has been considered as a viable option to overcome this problem. However, the molecular mechanisms underlying lignin formation in wheat biomass has not been studied. Combining molecular and biochemical approaches, the present study investigated the transcriptional regulation of lignin biosynthesis in two wheat cultivars with varying lodging characteristics and also in response to waterlogging. It also examined the association of lignin level in tissues with that of plant hormones implicated in the control of lignin biosynthesis. RESULTS: Analysis of lignin biosynthesis in the two wheat cultivars revealed a close association of lodging resistance with internode lignin content and expression of 4-coumarate:CoA ligase1 (4CL1), p-coumarate 3-hydroxylase1 (C3H1), cinnamoyl-CoA reductase2 (CCR2), ferulate 5-hydroxylase2 (F5H2) and caffeic acid O methyltransferase2 (COMT2), which are among the genes highly expressed in wheat tissues, implying the importance of these genes in mediating lignin deposition in wheat stem. Waterlogging of wheat plants reduced internode lignin content, and this effect is accompanied by transcriptional repression of three of the genes characterized as highly expressed in wheat internode including phenylalanine ammonia-lyase6 (PAL6), CCR2 and F5H2, and decreased activity of PAL. Expression of the other genes was, however, induced by waterlogging, suggesting their role in the synthesis of other phenylpropanoid-derived molecules with roles in stress responses. Moreover, difference in internode lignin content between cultivars or change in its level due to waterlogging is associated with the level of cytokinin. CONCLUSION: Lodging resistance, tolerance against biotic and abiotic stresses and feedstock quality of wheat biomass are closely associated with its lignin content. Therefore, the findings of this study provide important insights into the molecular mechanisms underlying lignin formation in wheat, an important step towards the development of molecular tools that can facilitate the breeding of wheat cultivars for optimized lignin content and enhanced feedstock quality without affecting other lignin-related agronomic benefits. PMID- 26811088 TI - Budd-Chiari Syndrome in Young Chinese: Clinical Characteristics, Etiology and Outcome of Recanalization from a Single Center. AB - PURPOSE: We aimed to characterize the clinical profile, etiology, and outcomes of young Chinese patients with Budd-Chiari syndrome treated with recanalization. METHODS: A total of 35 consecutive young patients (<=25 years of age) with primary Budd-Chiari syndrome treated with recanalization at our center were enrolled in this study between March 2011 and December 2014. Data on baseline information, etiology tests, therapeutic recanalization strategies, and follow-up were collected. RESULTS: The most common clinical feature was ascites, present in 33 cases (94%). Hepatic vein obstruction was present in 60% (21/35) of patients, inferior vena cava obstruction in 3% (1/35), and combined obstruction in 37% (13/35). The most common risk factor for thrombosis was hyperhomocysteinemia (14/35, 40%). Recanalization was technically successful in 32 of 35 patients (91%), and clinically successful in 28 of these 32 patients (88%). The cumulative 1- and 3-year primary patency rates were 75.2 and 54.3%, respectively. The cumulative 1- and 3-year secondary patency rates were 89.3 and 89.3%, respectively. The cumulative 1- and 3-year survival rates were 96.9 and 93.8%, respectively. CONCLUSION: In this study, the most common type of lesion was hepatic vein obstruction, the most common thrombotic risk factor was hyperhomocysteinemia, and recanalization resulted in good mid-term outcomes in young Chinese patients with Budd-Chiari syndrome. PMID- 26811090 TI - Potential Ergogenic Effects of Saffron. AB - Crocus sativus, commonly known as saffron, is a rich source of carotenoids with many health benefits. The muscular strength, pulmonary function, and reaction time are vital to the athlete's performance, and this study aimed to investigate an ergogenic effect of saffron. Twenty-eight nonactive and healthy male university students were randomly assigned into the saffron (n = 14) and control (n = 15) groups. The experimental group received dried saffron stigma (300 mg/day for 10 days) and the control group received a placebo. After one session, familiarization with the tests, anthropometric parameters, visual and audio reaction times, and the maximum isometric and isotonic forces on a leg press machine were measured accordingly, 1 day before and after the supplementation period. This study shows that 10 days of supplementation with saffron significantly increased (10.1%) the isometric force (p < .0001; effect size (EF) = 0.432) and increased 6.1% the isotonic force (p < .0001; effect size = 0.662), as well as effecting faster visual (p < .05; EF = 0.217) and audio (p < .05; EF = 0.214) reaction times. The ergogenic effect of saffron (increase in the forces) may contribute to increase in the muscle mitochondrial biogenesis and positive effect on the motor cortex, both of which may explain faster audio and visual reaction times. Saffron supplementation was also possibly responsible for improvement of muscle blood perfusion and facilitation in the oxygen transport. PMID- 26811092 TI - Remember Keppra: seizure control with subcutaneous levetiracetam infusion. PMID- 26811093 TI - A novel SETX gene mutation producing ataxia with oculomotor apraxia type 2. PMID- 26811094 TI - Teaching neuroimages: 'Blind drunk': neuroimaging findings in methanol poisoning. PMID- 26811095 TI - Solamargine production by a fungal endophyte of Solanum nigrum. AB - AIMS: The aim was to isolate, identify and characterize endophytes from Solanum nigrum L. as a new source of the cytotoxic steroidal alkaloid solamargine. METHODS AND RESULTS: Three endophytic fungi; SNFSt, SNFL and SNFF were isolated from S. nigrum and identified by molecular methods. Preliminary TLC screening showed a common metabolite between the plant and one of these fungi, SNFSt which was identified as Aspergillus flavus based on the phylogenetic analysis of its ITS sequence. Subsequent LC-HRESIMS analysis unambiguously established the identity of the compound based on its molecular formula and its characteristic MS(2) fragmentation pattern as solamargine. To ascertain its identity, fungal solamargine was isolated using preparative TLC and its structure was fully characterized using NMR spectroscopic techniques and high-resolution mass spectrometric analysis. Solamargine production could be followed and quantified for a total of 11 generations of this fungus with a titer of ~250-300 MUg l(-1) . This study represents one of the first examples where host plant-derived compounds have been demonstrated to be steadily produced by an endophytic fungi in sizeable quantities. CONCLUSIONS: The production of solamargine (found in the host plant) by a cultivable fungal endophyte at a significant yield is a new observation. Further experiments such as media optimization, OSMAC (One Strain Many Compounds) or epigenetic modifiers could be applied to enhance the fungal solamargine production. SIGNIFICANCE AND IMPACT OF THE STUDY: The endophytic fungus SNFSt isolated from S. nigrum may be utilized for quantitative production of the potent cytotoxic metabolite solamargine. PMID- 26811097 TI - Healthcare justice and human rights in perinatal medicine. AB - This article describes an approach to ethics of perinatal medicine in which "women and children first" plays a central role, based on the concept of healthcare justice. Healthcare justice requires that all patients receive clinical management based on their clinical needs, which are defined by deliberative (evidence-based, rigorous, transparent, and accountable) clinical judgment. All patients in perinatal medicine includes pregnant, fetal, and neonatal patients. Healthcare justice also protects the informed consent process, which is intended to empower the exercise of patient autonomy in the decision making process about patient care. In the context of healthcare justice, the informed consent process should not be influenced by ethically irrelevant factors. Healthcare justice should be understood as a basis for the human rights to healthcare and to participate in decisions about one's healthcare. Healthcare justice in perinatal medicine creates an essential role for the perinatologist to be an effective advocate for pregnant, fetal, and neonatal patients, i.e., for "women and children first." PMID- 26811100 TI - Anti-tumor effect of ultrasound-induced Nordy-loaded microbubbles destruction. AB - BACKGROUND: Synthesized dl-Nordihydroguaiaretic acid (dl-NGDA or "Nordy") can inhibit the growth of malignant human tumors, especially the tumor angiogenesis. However, its liposoluble nature limits its in vivo efficacy in the hydrosoluble circulation of human. PURPOSE: We tried to use the ultrasonic microbubble as the carrier and the ultrasound-induced destruction for the targeted release of Nordy and evaluate its in vitro and in vivo anti-tumor effect. METHODS: Nordy-loaded lipid microbubbles were prepared by mechanical vibration. Effects of ultrasound induced Nordy-loaded microbubbles destruction on proliferation of human umbilical vein endothelial cells (HUVECs), tumor derived endothelial cells (Td-ECs), and rabbit transplanted VX2 tumor models were evaluated. RESULTS: The ultrasound induced Nordy-loaded microbubbles destruction inhibited the proliferations of HUVECs and Td-ECs in vitro, and inhibited the tumor growth and the microvasculature in vivo. Its efficacy was higher than those of Nordy used only and Nordy with ultrasound exposure. CONCLUSION: Ultrasonic microbubbles can be used as the carrier of Nordy and achieve its targeted release with improved anti tumor efficacy in the condition of ultrasound-induced microbubbles destruction. PMID- 26811101 TI - Hydrogen sulfide protects against cognitive impairment induced by hepatic ischemia and reperfusion via attenuating neuroinflammation. AB - Previously, hepatic ischemia followed by reperfusion (hepatic I/R) has been found to cause cognitive impairment. Hydrogen sulfide (H2S) attenuates hepatectomy induced cognitive deficits and also protects against cognitive dysfunction induced by neurodegenerative diseases. In this study, we aim to determine whether sodium hydrosulfide (NaHS), a H2S donor, could alleviate hepatic I/R-induced cognitive impairment and the underlying mechanisms. Rats were injected intraperitoneally with NaHS (5 mg/kg/d) for 11 days. A segmental hepatic I/R model was established on the fourth day. Cognitive function, proinflammatory cytokines levels, and hippocampal ionized calcium-binding adaptor molecule 1 (Iba1) expression was analyzed. We found hepatic I/R increased proinflammatory cytokines levels in serum and hippocampus, up-regulated Iba1 expression, leading to cognitive impairment in rats. However, treatment with NaHS alleviated hepatic I/R induced these neuroinflammatory changes and effectively improved cognitive function. Thus, NaHS appears to protect against cognitive impairment in rats undergoing hepatic I/R by attenuating neuroinflammation in the hippocampus. PMID- 26811102 TI - Bone marrow-derived mesenchymal stem cells effectively regenerate fibrotic liver in bile duct ligation rat model. AB - Mesenchymal stem cells (MSCs) have attracted lots of attention for the treatment of acute liver failure and end-stage liver diseases. This study aimed at investigating the fundamental mechanism by which bone marrow-derived MSCs (BM MSCs) induce liver regeneration of fibrotic liver in rats. Rats underwent bile duct ligation (BDL) surgery and four weeks later they were treated with either BM MSCs (3 * 10(6) cells /rat, once, tail vein injection) or silymarin (100 mg/kg, daily, orally) for four weeks. Liver function tests and hepatic oxidative stress were determined. Hepatic injury and fibrosis were assessed by H and E, Sirus red staining and immunohistochemical expression of alpha-smooth muscle actin (alpha SMA). Hepatocyte growth factor (HGF) and the gene expression of cytokeratin-19 (CK-19) and matrix metalloproteinase-2 (MMP-2) in liver tissue were determined. BDL induced cholestatic liver injury characterized by elevated ALT and AST activities, bilirubin and decreased albumin. The architecture damage was staged as Metavir score: F3, A3. Fibrosis increased around proliferating bile duct as indicated by sirus red staining and alpha-SMA immunostaining. Fibrogenesis was favored over fibrolysis and confirmed by decreased HGF with increased expression of CK-19, but decreased MMP-2 expression. BM-MSCs treatment restored deteriorated liver functions and restored the histological changes, resolved fibrosis by improving liver regenerative capabilities (P < 0.001), increases in HGF and MMP-2 mRNA and downregulating CK-19 mRNA. Sliymarin, however, induced similar but less prominent effects compared to BM-MSCs. In conclusion, liver regenerative capabilities can be stimulated by BM-MSCs via augmentation of HGF that subsequently up-regulate MMP-2 mRNA while downregulating CK-19 mRNA. PMID- 26811105 TI - Comparative Analysis of the Trace Element Content of the Leaves and Roots of Three Plantago Species. AB - The primary objective of this study is to perform a comparative analysis of the trace element content of the leaves and roots of three Plantago species (P. maxima Juss. ex Jacq., P. major L., and P. lanceolata L.). Trace element levels were assessed by inductively coupled plasma mass spectrometry. The data indicate that the leaves of P. lanceolata are characterized by the highest Co, Cr, and Se content, whereas P. maxima leaves contained the greatest levels of Si and Zn. In contrast, the highest concentrations of Co, Cr, Fe, I, Mn, Si, and V were detected in the roots of P. major. Zn content was also higher in P. maxima roots than in the other species analyzed. The toxic trace elements were differentially distributed across the studied species. In particular, P. lanceolata leaves contained significantly higher Al, As, Li, Ni, Pb, and Sr levels, whereas the B and Cd content was elevated in P. major as compared to the other species. Surprisingly, the leaf Hg level was the lowest in P. major, whose levels of Al, As, B, Cd, Ni, Li, and Sr were significantly higher than the other two species. The data indicate that the concentration of most of the essential trace elements was higher in the leaves and roots of P. major and P. lanceolata than in P. maxima, while P. maxima had less toxic metals. The obtained data on trace elements content in Plantago tissues may be taken into account while using plant preparations in practical medicine. PMID- 26811103 TI - Women may respond different from men to vitamin D supplementation regarding cardiometabolic biomarkers. AB - Evidence has revealed that vitamin D status is associated with the cardiometabolic risk factors. Moreover, few gender-specific analyses have been performed in the clinical trials regarding vitamin D supplementation. As a result, assessing gender differences regarding the effects of vitamin D supplementation on some cardiometabolic biomarkers in patients with non-alcoholic fatty liver disease (NAFLD) was the aim of present study. We conducted a post hoc subgroup analysis of a double blind placebo controlled study. Patients with NAFLD randomly allocated to receive one oral pearl consisting of 50,000 IU vitamin D3 (n = 27, 13 men and 14 women) or a placebo (n = 26, 13 men and 13 women) every 14 days for four months. Serum lipid profiles, aminotransferases, high-sensitive C reactive protein (hs-CRP), adiponectin as well as insulin resistance and dietary intakes were assessed pre- and post-study. In both genders, serum 25(OH) D3 increased significantly (P < 0.001). This increase was accompanied by significant decrease in serum total cholesterol (TC) (% of change: -7% in vitamin D vs. + 0.4% in placebo, P = 0.04) and LDL-C (%of change: -9.6% in vitamin D vs. -4% in placebo, P = 0.006) in women. However, in men, vitamin D supplementation increased the levels of serum TC (% of change: +9.2% in vitamin D vs. -10% in placebo, P = 0.02) with no significant effects on LDL-C. Moreover, vitamin D significantly reduced serum hs-CRP in women. The median daily calcium intake in both genders was well below the dietary reference intake for adults. In conclusion, improved vitamin D status might decrease serum TC and LDL-C levels as well as hs-CRP in women with NAFLD. However, it might increase serum TC in men who have low daily calcium intake. Further studies with larger sample sizes are needed to confirm these results. PMID- 26811106 TI - Metal Ion Imbalance-Related Oxidative Stress Is Involved in the Mechanisms of Liver Injury in a Rat Model of Chronic Aluminum Exposure. AB - The objective of the study is to investigate the effects of chronic aluminum overload on rat liver function and its induction of pathological changes in metal ion levels and oxidative stress in hepatic tissues. Wistar rats were intragastrically administered aluminum gluconate (200 mg Al(3+)/Kg) once a day, 5 days a week, for 20 weeks. HE staining was used to visualize pathological changes in rat liver tissue. A biochemical method was adopted to detect ALT, AST, ALP, and GGT levels, as well as liver SOD activity and blood plasma MDA content. A plasma atomic emission spectrophotometer was used to detect Al, Mn, Fe, Zn, and Cu ion contents in liver tissue. Our results showed obvious vacuolar degeneration, granular degeneration, and spotty necrosis in chronic Al-overload rat hepatocytes. The levels of ALT, AST, ALP, and GGT were significantly increased. Liver SOD activity was significantly decreased, and MDA content was significantly increased. In Al-overload rat liver, Al, Mn, Fe, and Cu contents were significantly increased, and in Al-overload rat serum, Mn, Fe, Zn, and Cu contents were significantly decreased. However, the Al level in Al-overload rat serum was not significantly different from that in control rat serum. These results suggest that chronic aluminum overload causes obvious damage to rat liver and causes imbalances in Al, Mn, Fe, Zn, and Cu levels in rat liver and serum. Metal ion imbalance-related oxidative stress may be involved in the mechanism of chronic liver injury caused by aluminum overload. PMID- 26811107 TI - Anti-Proliferative Effect of Copper Oxide Nanorods Against Human Cervical Carcinoma Cells. AB - Metal oxide nanoparticles have been widely investigated for its use in the pharmacological field. The present study was aimed to investigate the cytotoxicity of copper oxide nanorods in human cervical carcinoma cells. The effect of copper oxide nanorods on cell viability was determined by sulforhodamine-B (SRB) assay. The fluorescence and confocal microscopy analyzes showed the cell rounding and nuclear fragmentation following exposure of copper oxide nanorods. Reactive oxygen species (ROS) was increased and could initiate membrane lipid peroxidation, which in turn regulate cytokinetic movements of cells. The messenger RNA (mRNA) expression of p53 and caspase 3 was increased, which further confirms the occurrence of apoptosis at the transcriptional level. Furthermore, caspase-3 enzyme activity was increased, which also confirms the occurrence of apoptosis in tumor cells at the translational level. Taking all our experimental results together, it may suggest that the copper oxide nanorods could be a potential anti-tumor agent to inhibit cancer cell proliferation. PMID- 26811108 TI - Zinc as an adjunct to antibiotics for the treatment of severe pneumonia in children <5 years: a meta-analysis of randomised-controlled trials. AB - The effect of Zn, as an adjunct to antibiotics, on the treatment of severe pneumonia in young children is still under debate; therefore, we performed a meta analysis to evaluate the therapeutic role of Zn for severe pneumonia in children younger than 5 years. PubMed, Cochrane library and Embase databases were systematically searched from inception until October 2015 for randomised controlled trials (RCT) that assessed the effect of Zn as an adjunct to antibiotics for severe pneumonia. Random-effects model was used for calculating the pooled estimates, and intention-to-treat principle was also applied. Nine RCT involving 2926 children were included. Overall, the pooled results showed that adjunct treatment with Zn failed to reduce the time to recovery from severe pneumonia (hazard ratios (HR)=1.04; 95% CI 0.90, 1.19; I(2)=39%; P=0.58), hospital length of stay (HR=1.04; 95% CI 0.83, 1.33; I(2)=57%; P=0.74), treatment failure (relative risk (RR)=0.95; 95% CI 0.79, 1.14; I(2)=20%; P=0.58) or change of antibiotics (RR=1.07; 95% CI 0.79, 1.45; I(2)=44%; P=0.67). In addition, continuous outcomes were consistent while meta-analysed with standard mean difference, and all outcomes remained stable in intention-to-treat analysis. No significant differences were observed in the two groups between death rate, adverse events or recovery times of severe pneumonia indicators. Our results suggested that adjunct treatment with Zn failed to benefit young children in the treatment of severe pneumonia. Considering the clinical heterogeneity, baseline characteristics of children, definition of severe pneumonia and Zn supplement way should be taken into consideration in future research. This study was registered at PRESPERO as CRD42015019798. PMID- 26811109 TI - Translational research on influenza virus infection using a nonhuman primate model. AB - Influenza virus infection is a seasonal infectious disease for humans, whereas it is also a zoonosis that is originally transmitted from animals to humans. Therefore, several animal models are used in research on influenza virus infection. We have used a nonhuman primate (NHP) model to extrapolate pathogenicity of various influenza viruses and efficacy of vaccines and antiviral drugs against the influenza viruses in humans. NHPs have genes, anatomical structure, and immune responses similar to those of humans as compared to other animal models. Using an NHP model, we revealed that the pandemic 2009 influenza A virus caused viral pneumonia as reported in human patients. Thus, it is thought that NHP models can be used to predict replication of emerging viruses in humans. We also examined the pathogenicity of highly pathogenic avian influenza viruses and evaluated a new therapeutic antibody in macaques under an immunocompromised condition. NHP models have provided promising results in research on other infectious diseases including Ebola virus and human/simian immunodeficiency virus infections. Thus, NHPs are important in biomedical research for determining the pathogenesis and for development of treatments, especially when clinical trials are difficult. We summarize the characteristics and advantages of research using NHP models in this review. PMID- 26811110 TI - Erratum to: Rectocutaneous fistula with transmigration of the suture: a rare delayed complication of vault fixation with the sacrospinous ligament. AB - There was an oversight in the Authorship of a recent Images in Urogynecology article titled: Rectocutaneous fistula with transmigration of the suture: a rare delayed complication of vault fixation with the sacrospinous ligament (DOI 10.1007/ s00192-015-2823-5). We would like to include Adj A/P Han How Chuan's name in the list of authors. Adj A/P Han is a Senior Consultant and Department Head of Urogynaecology at the KK Hospital for Women and Children, Singapore. PMID- 26811111 TI - Rectovaginal fistula repair using a gracilis muscle flap. AB - INTRODUCTION AND HYPOTHESIS: This video demonstrates a technique for using a pedicled gracilis muscle flap to repair rectovaginal fistula. METHODS: We present the case of a 48-year-old woman diagnosed with rectal cancer 2 years earlier. She underwent neoadjuvant chemoradiation followed by ultralow anterior resection. Six weeks after surgery, a fistula was identified at the anastomotic site. Preoperative planning with urogynecology, plastic surgery, and colon and rectal surgery teams deemed a pedicled gracilis muscle flap to be the best approach for this patient due to the rich blood supply and the patient's prior history of pelvic irradiation. The gracilis muscle is suitable due to the proximity of its vascular pedicle to the perineum, length, and minimal functional donor-site morbidity. We discuss techniques used to interpose a gracilis muscle flap between the rectum and vagina to repair a rectovaginal fistula. CONCLUSION: Using the gracilis muscle is a viable option for repairing rectovaginal fistulas, especially in the setting of prior pelvic radiation. A multispecialty approach may be beneficial in complex cases to determine the optimal approach for repair. PMID- 26811112 TI - Predictors of vaginal mesh exposure after midurethral sling placement: a case control study. AB - INTRODUCTION AND HYPOTHESIS: Female stress urinary incontinence is highly prevalent, and synthetic midurethral sling placement is the most common type of anti-incontinence surgery performed in the USA. We aimed to identify risk factors associated with surgery used to treated vaginal mesh exposure after midurethral sling placement for stress urinary incontinence. METHODS: We identified women who underwent anti-incontinence procedures from January 2002 through December 2012. Patients with vaginal mesh exposure undergoing surgical repair after midurethral sling placement were compared with a control group without mesh exposure in a 1:3 ratio. Patients with ObTape sling placement (Mentor Corporation) were excluded. Logistic regression models were used to evaluate associations between clinical risk factors and vaginal mesh exposure. RESULTS: Overall, 2,123 patients underwent primary sling placement, with 27 (1.3 %) having vaginal mesh exposure necessitating surgical repair. Patients with mesh exposure were more likely to have undergone previous bariatric surgery (P = 0.008), hemoglobin <13 g/dL (P = 0.006), premenopausal status (P = 0.008), age <50 years (P = 0.001), and the retropubic approach to sling placement (P = 0.03). Multivariate analysis identified these risk factors: previous bariatric surgery (odds ratio [OR], 7.0; 95 % CI, 1.1-61.4), retropubic approach (OR, 5.7; 95 % CI, 1.1-107.0), preoperative hemoglobin <13 g/dL (OR, 2.8; 95 % CI, 1.1-7.5), and premenopausal status (OR, 2.6; 95 % CI, 1.0-7.3). Among postmenopausal patients, those with mesh exposure were significantly more likely to receive preoperative estrogen therapy (OR, 12.4; 95 % CI, 2.7-57.8). CONCLUSIONS: Previous bariatric surgery, retropubic approach, premenopausal status, and lower preoperative hemoglobin were associated with a significantly increased risk of surgery for vaginal mesh exposure after midurethral sling placement. Recognizing these factors can improve preoperative patient counseling. PMID- 26811113 TI - Effect of anesthesia type on perioperative outcomes with a midurethral sling. AB - INTRODUCTION AND HYPOTHESIS: There is no consensus on the most appropriate type of anesthesia for placement of a midurethral sling. Our objective was to compare intra- and perioperative outcomes for this procedure performed under general anesthesia versus monitored anesthesia care. METHODS: Retrospective cohort analysis of women undergoing outpatient placement of synthetic retropubic midurethral sling under general anesthesia (n = 141) or monitored anesthesia care (n = 84). Patients undergoing concomitant procedures were excluded. Primary outcome was operating room time. Secondary outcomes included surgical and recovery times, cost, discharge home with a catheter, and postoperative pain and/or nausea. RESULTS: In the general anesthesia group, both operating room time (mean +/- SD, 67.6 +/- 13.3 min vs 56.9 +/- 11.8 min, p < 0.001) and recovery room time (240.0 +/- 69.8 min vs 190.1 +/- 78.3 min, p < 0.001) were longer, whereas there was no difference in surgical time (30.0 +/- 8.9 min vs 29.0 +/- 9.7 min, p = 0.43). Cost was significantly higher in the general anesthesia group ($4,095 +/- 715 vs $3,877 +/- 777, p = 0.03). There was no difference in rates of bladder perforation (6.4 % vs 11.9 %, p = 0.33). Patients who underwent general anesthesia had higher rates of discharge with a catheter (27.0 % vs 15.8 %, p = 0.04). CONCLUSION: Monitored anesthesia care may offer significant benefits over general anesthesia in women undergoing retropubic midurethral sling, including shorter operating room and recovery times, lower costs, and less voiding dysfunction in the immediate postoperative period. PMID- 26811115 TI - Quantitative analyses of variability in normal vaginal shape and dimension on MR images. AB - INTRODUCTION AND HYPOTHESIS: We present a technique for quantifying inter individual variability in normal vaginal shape, axis, and dimension, and report findings in healthy women. METHODS: Eighty women (age: 28~70 years) with normal pelvic organ support underwent supine, multi-planar proton-density MRI. Vaginal width was assessed at five evenly-spaced locations, and vaginal axis, length, and surface area were quantified via ImageJ and MATLAB. RESULTS: The mid-sagittal plane angles, relative to the horizontal, of three vaginal axes were 90 +/- 11, 72 +/- 21, and 41 +/- 22 degrees (caudal to cranial, p < 0.001). The mean (+/- SD) vaginal widths were 17 +/- 5, 24 +/- 4, 30 +/- 7, 41 +/- 9, and 45 +/- 12 mm at the five locations (caudal to cranial, p < 0.001). Mid-sagittal lengths for anterior and posterior vaginal walls were 63 +/- 9 and 98 +/- 18 mm respectively. The vaginal surface area was 72 +/- 21 cm(2) (range: 34 ~ 164 cm(2)). The coefficient of determination between any demographic variable and any vaginal dimension did not exceed 0.16. CONCLUSIONS: Large variations in normal vaginal shape, axis, and dimensions were not explained by body size or other demographic variables. This variation has implications for reconstructive surgery, intravaginal and surgical product design, and vaginal drug delivery. PMID- 26811114 TI - The human urinary microbiome and how it relates to urogynecology. AB - INTRODUCTION AND HYPOTHESIS: Recent studies applying molecular techniques have demonstrated the presence of a urinary microbiota not detected by standard microbiological techniques. These have been found in the urine of healthy individuals and in those suffering from clinical symptoms. The present article reviews the findings of these studies to date, describing the molecular techniques, and specifically outlining any differences in microbiomes in relation to urogynecological disease. Further, the role of commensal bacteria in the lower urinary tract is considered. METHODS: An extensive literature search was conducted to identify articles on the microbiome of the female urinary tract in health and disease. We searched the electronic meta-databases Ovid MEDLINE(r) 1946-2015 and Embase 1974-2015. The keywords "microbiome, microbiota, bacterial colonization, microbiology, commensal bacteria, and bacteriuria" were searched in combination with "lower urinary tract symptoms, urogenital symptoms, urinary tract infection, overactive bladder and urinary incontinence." A total of 426 papers were retrieved; 33 were included in this paper. RESULTS: The microbiome of the female lower urinary tract shows variance between individuals and between age groups. There are significant differences between the microbiota in the lower urinary tract of individuals with urological symptoms and those without, relating to type and proportion of commensal Lactobacillus spp. There is only weak evidence to suggest that Lactobacillus might be applied as a therapeutic measure. CONCLUSIONS: It is still unclear what role microbiota plays in female urinary tract health. The discovery of bacteria in the urine of healthy individuals may have implications for future therapies for lower urinary tract symptoms. PMID- 26811116 TI - High urinary flow in women with stress incontinence: corrected flow-age nomogram evaluation after a transobturator tape procedure. AB - INTRODUCTION AND HYPOTHESIS: We noninvasively compared urinary flow in both pre- and post-transobturator tape (TOT) procedures in stress urinary incontinence (SUI) patients using previously reported corrected flow-age nomograms in healthy women. METHODS: This retrospective cohort study included patients who underwent a successful TOT procedure to treat SUI. Non-instrumented uroflowmetry was performed before and 3 months after surgery. Corrected maximum flow rate (cQmax) and average flow rate (cQave) were calculated using Qmax/?voided volume (VV) and Qave/?VV respectively. The ratio of corrected flow to age-adjusted corrected flow in healthy women was calculated in each patient. Each parameter was compared against pre-TOT and 3-months post-TOT values. RESULTS: Sixty-two patients were eligible for study inclusion. All urinary flow parameters were significantly higher pre-TOT than at 3 months post-TOT. The number of patients with cQmax and cQave over mean flow-age nomogram, compared with healthy women, before the TOT procedure decreased 3 months post-TOT; however, in many patients, cQmax and cQave were higher than in the corrected flow-age nomogram post-TOT. No significant difference in the ratio of cQmax to age-adjusted cQmax between pre- and post-TOT in the normal urinary flow group was observed, but significantly decreased in the high urinary flow group 3 months after TOT. CONCLUSIONS: Urinary flow rates were higher in SUI patients compared with age-matched controls and successful TOT procedures normalized urinary flows in patients with high urinary flow. A simple evaluation of urinary flow using a corrected flow-age nomogram may be clinically useful in SUI patients. PMID- 26811117 TI - Assembly of 1D, 2D and 3D lanthanum(iii) coordination polymers with perchlorinated benzenedicarboxylates: positional isomeric effect, structural transformation and ring-opening polymerisation of glycolide. AB - Utilizing a series of positional isomers of tetrachlorinated benzenedicarboxylic acid ligands, seven La(iii)-based coordination polymers were solvothermally synthesized and structurally characterized. Their structural dimensionalities varying from 1D double chains, to the 2D 3,4,5-connected network, to 3D 6 connected pcu topological nets are only governed by the positions of carboxyl groups on the tetrachlorinated benzene ring. A comprehensive analysis and comparison reveals that the size of the carbonyl solvent molecules (DMF, DEF, DMA, and NMP) can affect the coordination geometries around the La(iii) ions, the coordination modes of carboxylate groups, the packing arrangements, and the void volumes of the overall crystal lattices. One as-synthesized framework further shows an unprecedented structural transformation from a 3D 6-connected network to a 3D 4,5-connected net through the dissolution and reformation pathway in water, suggesting that these easily hydrolyzed lanthanide complexes may serve as precursors to produce new high-dimensional frameworks. The bulk solvent-free melt polymerisation of glycolide utilizing these La(iii) complexes as initiators has been reported herein for the first time. All complexes were found to promote the polymerization of glycolide over a temperature range of 200 to 220 degrees C, producing poly(glycolic acid) (PGA) with a molecular weight up to 93,280. Under the same experimental conditions, the different catalytic activities for these complexes may result from their structural discrepancy. PMID- 26811118 TI - Lean interventions in healthcare: do they actually work? A systematic literature review. AB - PURPOSE: Lean is a widely used quality improvement methodology initially developed and used in the automotive and manufacturing industries but recently expanded to the healthcare sector. This systematic literature review seeks to independently assess the effect of Lean or Lean interventions on worker and patient satisfaction, health and process outcomes, and financial costs. DATA SOURCES: We conducted a systematic literature review of Medline, PubMed, Cochrane Library, CINAHL, Web of Science, ABI/Inform, ERIC, EMBASE and SCOPUS. STUDY SELECTION: Peer reviewed articles were included if they examined a Lean intervention and included quantitative data. Methodological quality was assessed using validated critical appraisal checklists. Publically available data collected by the Saskatchewan Health Quality Council and the Saskatchewan Union of Nurses were also analysed and reported separately. DATA EXTRACTION: Data on design, methods, interventions and key outcomes were extracted and collated. RESULTS OF DATA SYNTHESIS: Our electronic search identified 22 articles that passed methodological quality review. Among the accepted studies, 4 were exclusively concerned with health outcomes, 3 included both health and process outcomes and 15 included process outcomes. Our study found that Lean interventions have: (i) no statistically significant association with patient satisfaction and health outcomes; (ii) a negative association with financial costs and worker satisfaction and (iii) potential, yet inconsistent, benefits on process outcomes like patient flow and safety. CONCLUSION: While some may strongly believe that Lean interventions lead to quality improvements in healthcare, the evidence to date simply does not support this claim. More rigorous, higher quality and better conducted scientific research is required to definitively ascertain the impact and effectiveness of Lean in healthcare settings. PMID- 26811119 TI - SOCS1 in cancer: An oncogene and a tumor suppressor. AB - The Suppressor Of Cytokine Signaling 1 (SOCS1) has been extensively investigated in immune cells where it works as a potent inhibitor of inflammation by negative feedback regulation of the cytokine-activated JAK-STAT signaling pathways. SOCS1 is also recognized as a tumor suppressor in numerous cancers and its critical functional relevance in non-immune cells, including epithelial cells, has just begun to emerge. Most notably, conflicting results from clinical and experimental studies suggest that SOCS1 may function as either a tumor suppressor or a tumor promoter, in a cell context-dependent manner. Here, we present an overview of the mechanisms underlying SOCS1 function as a tumor suppressor and discuss the emerging evidences of SOCS1 activity as an oncogene. PMID- 26811120 TI - The prevalence and clinical features of amphetamine-induced obsessive compulsive disorder. AB - BACKGROUND: Amphetamine abuse is increasing worldwide, and the occurrence of amphetamine-induced (AI) psychiatric issues further complicates treatment. In response, the DSM 5 has introduced the classification of amphetamine-induced obsessive-compulsive disorders (AI-OCD), though little has been published on either its prevalence rates or its clinical features. The aim of the present study was therefore to investigate the prevalence of AI-OCD, to describe patients' clinical features, and to compare the prevalence rate among such patients with those for OCD in the general population in Western countries and Iran. METHODS: A total of 547 patients with amphetamine abuse or dependency and with a positive urine test (mean age: 31.64 years; 75.5% males) took part in the study. A psychiatric interview was carried out, covering both socio-demographic and illness-related information. RESULTS: 18 (3.3%) patients suffered from OCD prior to amphetamine abuse, 491 (89.8%) had no OCD, and 38 (6.9%) suffered from AI-OCD. Neither socio-demographic nor illness-related dimensions predicted patients with diagnosed AI-OCD. The prevalence of AI-OCD was significantly higher than that for OCD in the general population (2.3% in Western countries, 1.8% in Iran). CONCLUSIONS: Data suggest that prevalence rate of AI-OCD is about 7%. Neither socio-demographic nor illness-related dimensions predicted the occurrence of AI-OCD. Thus, it remains unclear why some amphetamine abusers develop AI-OCD while others do not. PMID- 26811122 TI - [Interventions based on exercise and physical environment for preventing falls in cognitively impaired older people living in long-term care facilities: A systematic review and meta-analysis]. AB - This systematic review aims to report the effectiveness of interventions based on exercise and/or physical environment for reducing falls in cognitively impaired older adults living in long-term care facilities. In July 2014, a literature search was conducted using main databases and specialised sources. Randomised controlled trials assessing the effectiveness of fall prevention interventions, which used exercise or physical environment among elderly people with cognitive impairment living in long-term care facilities, were selected. Two independent reviewers checked the eligibility of the studies, and evaluated their methodological quality. If it was adequate, data were gathered. Fourteen studies with 3,539 participants using exercise and/or physical environment by a single or combined approach were included. The data gathered from studies that used both interventions showed a significant reduction in fall rate. Further research is needed to demonstrate the effectiveness of those interventions for preventing falls in the elderly with cognitive impairment living in long-term care establishments. PMID- 26811121 TI - Onset of opportunity to use cannabis and progression from opportunity to dependence: Are influences consistent across transitions? AB - BACKGROUND: There is a developing body of research looking at cannabis use opportunity, but little research examining timing of opportunity to use cannabis. AIMS: Identify factors associated with (1) earlier opportunity to use cannabis and (2) faster progression from opportunity to cannabis dependence. METHOD: Cross sectional study of 3824 Australian twins and siblings, measuring age of onset of cannabis use opportunity and DSM-IV cannabis dependence. Survival analysis identified factors associated with faster progression to opportunity or dependence. RESULTS: Factors associated with both speed of progression to opportunity and dependence were conduct disorder (opportunity HR 5.57, 95%CI 1.52 20.47; dependence HR 2.49, 95%CI 1.91-3.25), parental drug problems (opportunity HR 7.29, 95%CI 1.74-30.62; dependence HR 3.30, 95%CI 1.63-6.69), weekly tobacco use (opportunity HR 8.57, 95%CI 3.93-18.68; dependence HR 2.76, 95% CI 2.10 3.64), and female gender (opportunity HR 0.69, 95%CI 0.64-0.75; dependence HR 0.44, 95%CI 0.34-0.55). Frequent childhood religious attendance (HR 0.74, 95%CI 0.68-0.80), parental conflict (HR 1.09, 95%CI 1.00-1.18), parental alcohol problems (HR 1.19, 95%CI 1.08-1.30) and childhood sexual abuse (HR 1.17, 95%CI 1.01-1.34) were uniquely associated with transition to opportunity. Depressive episode (HR 1.44, 95%CI 1.12-1.85), tobacco dependence (HR 1.36, 95%CI 1.04 1.78), alcohol dependence (HR 2.64, 95%CI 1.53-4.58), other drug use (HR 2.10, 95%CI 1.64-2.69) and other drug dependence (HR 2.75, 95%CI 1.70-4.43) were uniquely associated with progression to dependence. CONCLUSION: The profile of factors associated with opportunity to use cannabis and dependence only partially overlaps, suggesting targeting of interventions may benefit from being tailored to the stages of drug use. PMID- 26811124 TI - Near-Barrierless Ammonium Bisulfate Formation via a Loop-Structure Promoted Proton-Transfer Mechanism on the Surface of Water. AB - In the atmosphere, a well-known and conventional pathway toward the formation of ammonium sulfate is through the neutralization of sulfuric acid with ammonia (NH3) in water droplets. Here, we present direct ab initio molecular dynamics simulation evidence of the formation of ammonium bisulfate (NH4HSO4) from the hydrated NH3 and SO3 molecules in a water trimer as well as on the surface of a water droplet. This reaction suggests a new mechanism for the formation of ammonium sulfate in the atmosphere, especially when the concentration of NH3 is high (e.g., ~10 MUg m(-3)) in the air. Contrary to the water monomer and dimer, the water trimer enables near-barrierless proton transfer via the formation of a unique loop structure around the reaction center. The formation of the loop structure promotes the splitting of a water molecule in the proton-transfer center, resulting in the generation a NH4(+)/HSO4(-) ion pair. The loop-structure promoted proton-transfer mechanism is expected to be ubiquitous on the surface of cloud droplets with adsorbed NH3 and SO3 molecules and, thus, may play an important role in the nucleation of aerosol particles (e.g., fine particles PM2.5) in water droplets. PMID- 26811123 TI - [Non-invasive ventilation in 'do-not-intubate' patients in a chronic disease hospital. One year follow-up study]. AB - Elderly patients with multiple morbidity and do not intubate (DNI) orders frequently present with acute respiratory failure. There are data supporting the effectiveness of non-invasive ventilation (NIV) in this context. Our chronic disease hospital developed an integrated care clinical pathway for the use of NIV in acute respiratory failure in the emergency room and wards in 2010. The aim of this study was to assess the outcome of NIV in patients with acute respiratory failure who had a DNI order in a sub-acute care hospital. METHODS: Observational, one year-follow up study. The main variables were in-hospital mortality and one year mortality. Other variables recorded were: demographics, clinical data, functional data, performance of daily life activities, dementia, arterial blood gases and re-admissions. RESULTS: The study included a total of 102 patients, of which 22% were in institutions. The mean age 81+/-7.47% males, with a Charlson index 3.7+/-1, and Barthel index 54+/-31. The overall mortality during the admission was 33% (34 patients). Among those patients ventilated outside the protocol indication, the mortality was significantly greater, at 71% (P>.05). Overall one-year survival rate was 46%. This survival rate was statistically higher in patients with obesity hypoventilation syndrome and a Barthel >50. CONCLUSIONS: NIV is a useful technique in a hospital for chronic patients in an elderly population with a therapeutic ceiling. Despite their disease severity and comorbidity, acceptable survival rates are achieved. A correct case selection is needed. Obesity hypoventilation syndrome and those with Barthel index >50 have a better prognosis. PMID- 26811125 TI - Structure-activity relationship for peptidic growth hormone secretagogues. AB - Growth hormone releasing peptides (GHRPs) could be widely used by cheating athletes because they produce growth hormone (GH) secretion, so may generate an ergogenic effect in the body. Knowledge of the essential amino acids needed in GHRP structure for interaction with the target biological receptor GHSR1a, the absorption through different administration routes, and the maintenance of pharmacological activity of potential biotransformation products may help in the fight against their abuse in sport. Several GHRPs and truncated analogues with the common core Ala-Trp-(D-Phe)-Lys have been studied with a radio-competitive assay for the GHSR1a receptor against the radioactive natural ligand ghrelin. Relevant chemical modifications influencing the activity for positions 1, 2, 3, and 7 based on the structure aa-aa-aa-Ala-Trp-(D-Phe)-Lys have been obtained. To test in vivo the applicability of the activities observed, the receptor assay activity in samples from excretion studies performed after nasal administration of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin was confirmed. Overall results obtained allow to infer structure-activity information for those GHRPs and to detect GHSR1a binding (intact GHRPs plus active metabolites) in excreted urines. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26811128 TI - Assessment of brain metabolite correlates of adeno-associated virus-mediated over expression of human alpha-synuclein in cortical neurons by in vivo (1) H-MR spectroscopy at 9.4 T. AB - In this study, we used proton-localized spectroscopy ((1) H-MRS) for the acquisition of the neurochemical profile longitudinally in a novel rat model of human wild-type alpha-synuclein (alpha-syn) over-expression. Our goal was to find out if the increased alpha-syn load in this model could be linked to changes in metabolites in the frontal cortex. Animals injected with AAV vectors encoding for human alpha-syn formed the experimental group, whereas green fluorescent protein expressing animals were used as the vector-treated control group and a third group of uninjected animals were used as naive controls. Data were acquired at 2, 4, and 8 month time points. Nineteen metabolites were quantified in the MR spectra using LCModel software. On the basis of 92 spectra, we evaluated any potential gender effect and found that lactate (Lac) levels were lower in males compared to females, while the opposite was observed for ascorbate (Asc). Next, we assessed the effect of age and found increased levels of GABA, Tau, and GPC+PCho. Finally, we analyzed the effect of treatment and found that Lac levels (p = 0.005) were specifically lower in the alpha-syn group compared to the green fluorescent protein and control groups. In addition, Asc levels (p = 0.05) were increased in the vector-injected groups, whereas glucose levels remained unchanged. This study indicates that the metabolic switch between glucose-lactate could be detectable in vivo and might be modulated by Asc. No concomitant changes were found in markers of neuronal integrity (e.g., N-acetylaspartate) consistent with the fact that alpha-syn over-expression in cortical neurons did not result in neurodegeneration in this model. We acquired the neurochemical profile longitudinally in a rat model of human wild-type alpha-synuclein (alpha-syn) over expression in cortical neurons. We found that Lactate levels were reduced in the alpha-syn group compared to the control groups and Ascorbate levels were increased in the vector-injected groups. No changes were found in markers of neuronal integrity consistent with the fact that alpha-syn over-expression did not result in frank neurodegeneration. PMID- 26811126 TI - Drinkers' memory bias for alcohol picture cues in explicit and implicit memory tasks. AB - BACKGROUND: Alcohol cues can bias attention and elicit emotional reactions, especially in drinkers. Yet, little is known about how alcohol cues affect explicit and implicit memory processes, and how memory for alcohol cues is affected by acute alcohol intoxication. METHODS: Young adult participants (N=161) were randomly assigned to alcohol, placebo, or control beverage conditions. Following beverage consumption, they were shown neutral, emotional and alcohol related pictures cues. Participants then completed free recall and repetition priming tasks to test explicit and implicit memory, respectively, for picture cues. Average blood alcohol concentration for the alcohol group was 74+/-13mg/dl when memory testing began. Two mixed linear model analyses were conducted to examine the effects of beverage condition, picture cue type, and their interaction on explicit and implicit memory. RESULTS: Picture cue type and beverage condition each significantly affected explicit recall of picture cues, whereas only picture cue type significantly influenced repetition priming. Individuals in the alcohol condition recalled significantly fewer pictures than those in other conditions, regardless of cue type. Both free recall and repetition priming were greater for emotional and alcohol-related cues compared to neutral picture cues. No interaction effects were detected. CONCLUSIONS: Young adult drinkers showed enhanced explicit and implicit memory processing of alcohol cues compared to emotionally neutral cues. This enhanced processing for alcohol cues was on par with that seen for positive emotional cues. Acute alcohol intoxication did not alter this preferential memory processing for alcohol cues over neutral cues. PMID- 26811130 TI - Consuming yellow pea fiber reduces voluntary energy intake and body fat in overweight/obese adults in a 12-week randomized controlled trial. AB - BACKGROUND & AIMS: The purpose of this randomized, double-blind, placebo controlled study was to assess the effects of yellow pea fiber intake on body composition and metabolic markers in overweight/obese adults. METHODS: Participants (9 M/41 F; age 44 +/- 15 y, BMI 32.9 +/- 5.9 kg/m2) received isocaloric doses of placebo (PL) or pea fiber (PF; 15 g/d) wafers for 12 weeks. Outcome measures included changes in anthropometrics, body composition (DXA), oral glucose tolerance test (OGTT), food intake (ad libitum lunch buffet), and biochemical indices. RESULTS: The PF group lost 0.87 +/- 0.37 kg of body weight, primarily due to body fat (-0.74 +/- 0.26 kg), whereas PL subjects gained 0.40 +/ 0.39 kg of weight over the 12 weeks (P = 0.022). The PF group consumed 16% less energy at the follow-up lunch buffet (P = 0.026), whereas the PL group did not change. During the OGTT, glucose area under the curve (AUC) was lower in PF subjects at follow-up (P = 0.029); insulin increased in both groups over time (P = 0.008), but more so in the PL group (38% higher AUC vs. 10% higher in the PF group). There were no differences in gut microbiota between groups. CONCLUSIONS: In the absence of other lifestyle changes, incorporating 15 g/day yellow pea fiber may yield small but significant metabolic benefits and aid in obesity management. Clinical Trial Registry: ClinicalTrials.gov NCT01719900. PMID- 26811129 TI - Diet and polycystic kidney disease: A pilot intervention study. AB - BACKGROUND & AIMS: Dietary sodium, protein, acid precursors, and water have been linked to cyst growth in polycystic kidney disease; yet, no studies in patients have examined the feasibility of using a dietary intervention that controls all of these factors. The aim of this study was to determine if a diet, appropriate for persons of most ages, reduces the excretion of sodium, urea, acid, and decreases mean urine osmolality while gaining acceptance by patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS: Twelve adults with ADPKD enrolled in a pre-post pilot feasibility study and served as their own controls. Individuals consumed their usual diet for one week then for four weeks followed an isocaloric diet lower in sodium and protein and higher in fruits, vegetables, and water. Three-day diet records and two 24-h urine samples were collected at baseline, week 2, and week 4 visits; blood pressure, weight, and serum were obtained at all three visits. A modified nutrition hassles questionnaire was completed on the last visit. RESULTS: During the dietary intervention, subjects (n = 11) consumed less sodium, protein, and dietary acid precursors 36%, 28%, and 99%, respectively, and increased fluid intake by 42%. Urinary sodium, urea, net acid excretion, osmoles, and osmolality decreased 20%, 28%, 20%, 37%, and 15%, respectively; volume increased 35%. Urine changes were in accord with the diet record. Ninety-one percent of participants reported that none of the hassles were worse than "somewhat severe", and most participants felt "somewhat confident" or "very confident" that they could manage the new diet. CONCLUSIONS: A majority of adult patients with ADPKD successfully prepared and followed a composite diet prescription with decreased sodium, protein, acid precursors, and increased fluid intake. This trail was registered at ClinicalTrials.gov (NCT01810614). PMID- 26811131 TI - Overcoming Problems in Confirmatory Factor Analyses of MTMM Data: The Correlated Uniqueness Model and Factorial Invariance. AB - The general model typically used in the confirmatory factor analysis (CFA) approach to multitrait-multimethod (MTMM) data is plagued with methodological problems and frequently results in improper or unstable solutions. Here we reanalyze data from a previously published study, demonstrating that this model may lead to inappropriate interpretations even when it does converge to a proper solution, and describe safeguards against this occurrence. The results support the correlated uniqueness model, diagnostic tests of the validity of CFA-MTMM solutions, the inclusion of external validity criteria in the MTMM design as described by Marsh (1988; 1989; Marsh & Bailey, 19911, and the application of factorial invariance to test the stability of CFA-MTMM solutions. More generally, we demonstrate the flexibility of the CFA-MTMM approach for testing a variety of construct validity issues. PMID- 26811132 TI - Remarks on Parallel Analysis. AB - We investigate parallel analysis (PA), a selection rule for the number-of-factors problem, from the point of view of permutation assessment. The idea of applying permutation test ideas to PA leads to a quasi-inferential, non-parametric version of PA which accounts not only for finite-sample bias but sampling variability as well. We give evidence, however, that quasi-inferential PA based on normal random variates (as opposed to data permutations) is surprisingly independent of distributional assumptions, and enjoys therefore certain non- parametric properties as well. This is a justification for providing tables for quasi inferential PA. Based on permutation theory, we compare PA of principal components with PA of principal factor analysis and show that PA of principal factors may tend to select too many factors. We also apply parallel analysis to so-called resistant correlations and give evidence that this yields a slightly more conservative factor selection method. Finally, we apply PA to loadings and show how this provides benchmark values for loadings which are sensitive to the number of variables, number of subjects, and order of factors. These values therefore improve on conventional fixed thresholds such as 0.5 or 0.8 which are used irrespective of the size of the data. PMID- 26811134 TI - Equality Constraints in Multiple Correspondence Analysis. AB - The application of equality constraints on the categories of a variable is a simple but useful extension of multiple correspondence analysis. Equality can be used to incorporate prior knowledge about the relations between categories. Categories may belong to the same variable, to different variables, or both. The simplest form of equality specifies that all variables receive identical data transforms. This is useful, for example, if the same variable is measured on many points of time. This article outlines a procedure to deal with unequal category numbers and with subsets of variables. Though the technical results are not difficult to derive, they are not very well-known. Some applications illustrate the method. PMID- 26811133 TI - A Graph Theoretic Criterion for Determining the Number of Clusters in a Data Set. AB - This article is concerned with procedures for determining the number of clusters in a data set. Most of the procedures or stopping rules currently in use involve finding internally coherent and externally isolated clusters, but do not derive from the formal structure of the respective clustering model. Based on the graph theoretic concepts of minimal spanning tree, maximal spanning tree, and homomorphic function, a new criterion is advanced that yields a well-defined clustering solution. Its performance in determining the number of clusters in several empirical data sets is evaluated by comparing it to four prominent stopping rules. It is shown that the proposed criterion not only possesses mathematically attractive properties but also may contribute to solving the number-of-clusters problem. PMID- 26811135 TI - The Glory of Suboptimal Factor Rotation: Why Local Minima in Analytic Optimization of Simple Structure are More Blessing Than Curse. AB - Yet another facet of factor indeterminacy rears its ugly head: Factor rotation algorithms do not generally find the best solutions of which they are capable. But when enriched with the capacity to conduct repeated searches from random starting positions, a rotation algorithm's propensity to converge to optima that are merely local can be fashioned into a seine for catching interpretively provocative rotations of the input factors that might otherwise elude discovery. PMID- 26811136 TI - An Examination of the Etiology of the Attitude-Behavior Relation for Goal Directed Behaviors. AB - The nature of the attitude-behavior relation was investigated by use of structural equation models in a cross-lagged panel design. The theory of reasoned action and an augmented version of the theory, which included the frequency and recency of past behavior as covariates, were tested. Respondents were 254 undergraduates who provided behavioral and psychological reactions over two points in time to two kinds of goal-directed behaviors: event-planned goals (i.e., trying to lose weight) and event-triggered goals (i.e., initiating a conversation with an attractive stranger). The findings show that the theory of reasoned action as classically formulated explains trying to lose weight well but initiating a conversation poorly. Further, the introduction of frequency and recency effects brings into question predictions under the theory of reasoned action. Theoretical implications of the results are discussed. A weighted least squares method is applied to the asymptotic covariance matrix based on appropriate polychoric and tetrachoric correlations. Variates are assumed measured on only ordinal scales. PMID- 26811137 TI - Remarks on the Study of the Variety of Individuals. AB - Techniques for the study of the variety of individuals are discussed. A contrast is pointed out between the study of mean performances and the study of covariations. These are two components of the performances of the individuals. For the study of the variety of individuals, instead of keeping these two components separate, these two components should be combined into a single analysis. Examples of techniques which combine these two components are discussed. PMID- 26811138 TI - Inflammation as a cause of venous thromboembolism. AB - Inflammatory markers are highly amenable to appraise and adjust and could already serve as a diagnostic indicator and also as a predictor of prognosis over the management of many health problems. Inflammation is implicated in venous thromboembolism (VTE). However there is still an intense curiosity about whether it is a cause or only a consequence of the thromboembolic process. The more likely scenario is that some inflammatory mediators contribute to the development of VTE, which per se induces an inflammatory reaction. Here we will review evidences supporting the role of inflammation as a cause of VTE. Genetic association studies have provided possible links between inflammation-related genetic variants, especially cytokines (e.g. IL-1, IL-4, IL-6, IL-10, and IL-13), and VTE, leading to establish the fundamental role of genetic background in predisposition to VTE and variable inflammatory processes in individuals. Additionally, several inflammation-related conditions including aging, autoimmune disease, cancer, cardiovascular diseases, hormone replacement therapy, infectious diseases, metabolic diseases, overweight or obesity, pregnancy or postpartum, respiratory diseases, and trauma have been associated with an increased risk of VTE. At this moment, despite their theoretical potential, to achieve the implementation of the inflammation-related laboratory tests in practice is a long task and future studies with larger sample sizes are required to address whether the properties of the inflammatory process, particularly intensity and duration, are useful in determining the risk of VTE and following outcomes. PMID- 26811139 TI - Chemotherapy induced thrombocytopenia in pediatric oncology. AB - Thrombocytopenia has long been recognized as a significant problem of cancer therapy, but there is still lack of consensus about the optimal approach to prophylaxis and/or treatment of this important complication. In pediatric oncology, since there are very few studies dedicated to this problem, the knowledge gap is even larger and no final conclusions or pediatric evidence based guidelines are available. Those guidelines that are available consist mostly of experts' personal opinions and data extrapolated from the adult studies. In this review we tried to summarize the existing data and approaches in chemotherapy induced thrombocytopenia (CIT) in pediatric oncology. PMID- 26811140 TI - Alcoholic beverages, obesity, physical activity and other nutritional factors, and cancer risk: A review of the evidence. AB - PURPOSE: Prevention is a priority in the fight against cancers, especially nutritional prevention. To update the levels of evidence of relationships between 10 nutritional factors and cancer risk, the scientific literature published from 2006 to 2014 was reviewed by an expert group. METHODS: Data from 133 meta analyses, pooled analyses or intervention trials were examined. Nearly 150 relationships between nutritional factors and cancer at various sites were evaluated. RESULTS: According to the evidence graded as convincing or probable, these factors were divided in two groups. Factors which increase the risk of cancer are alcoholic beverages, overweight and obesity, red meat and processed meat, salt and salted foods and beta-carotene supplements. Factors which decrease the risk of cancer are physical activity, fruits and vegetables, dietary fiber, dairy products and breastfeeding. CONCLUSION: Three main nutritional objectives should be attained to improve cancer prevention: to reduce alcoholic beverages consumption, to have a balanced and diversified diet and to be physically active. PMID- 26811142 TI - Factors Associated with Achieving Complete Mental Health among Individuals with Lifetime Suicidal Ideation. AB - The objective of this study was to identify factors associated with complete mental health among Canadians who had ever seriously considered suicide. Data for this study were obtained from Statistics Canada's 2012 Canadian Community Health Survey-Mental Health (N = 2,844). The outcome variable examined in this study was complete mental health and was analyzed using binary logistic regression. Of the 2,844 respondents with lifetime suicidal ideation, 1,088 (38.2%) had complete mental health (i.e., had flourishing mental health, no mental illness, and no suicidal ideation in the past 12 months). Those who had a confidant were seven times more likely to have complete mental health. Other factors associated with achieving complete mental health among formerly suicidal respondents include being older, being a woman, having higher income, use of religious coping, and never previously having a mental illness. Considering the importance of these protective factors in formulating public health policies will allow for a more wide-reaching approach to suicide prevention. PMID- 26811144 TI - Longitudinal stent deformation during coronary bifurcation stenting. AB - A distortion of implanted coronary stent along its longitudinal axis during coronary intervention is known as longitudinal stent deformation (LSD). LSD is frequently seen with newer drug eluting stents (DES), specifically with PROMUS Element stent. It is usually caused by impact of guide catheter tip, or following passage of catheters like balloon catheter, IVUS catheter, guideliner, etc. We hereby report a case of LSD during coronary bifurcation lesion intervention, using two-stents technique. Patient had acute stent thrombosis as a complication of LSD, which was successfully managed. PMID- 26811145 TI - Time-Lapse Retinal Ganglion Cell Dendritic Field Degeneration Imaged in Organotypic Retinal Explant Culture. AB - PURPOSE: To develop an ex vivo organotypic retinal explant culture system suitable for multiple time-point imaging of retinal ganglion cell (RGC) dendritic arbors over a period of 1 week, and capable of detecting dendrite neuroprotection conferred by experimental treatments. METHODS: Thy1-YFP mouse retinas were explanted and maintained in organotypic culture. Retinal ganglion cell dendritic arbors were imaged repeatedly using confocal laser scanning microscopy. Maximal projection z-stacks were traced by two masked investigators and dendritic fields were analyzed for characteristics including branch number, size, and complexity. One group of explants was treated with brain derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) added to the culture media. Changes in individual dendritic fields over time were detected using pair-wise comparison testing. RESULTS: Retinal ganglion cells in mouse retinal explant culture began to degenerate after 3 days with 52.4% surviving at 7 days. Dendritic field parameters showed minimal change over 8 hours in culture. Intra- and interobserver measurements of dendrite characteristics were strongly correlated (Spearman rank correlations consistently > 0.80). Statistically significant (P < 0.001) dendritic tree degeneration was detected following 7 days in culture including: 40% to 50% decreases in number of branch segments, number of junctions, number of terminal branches, and total branch length. Scholl analyses similarly demonstrated a significant decrease in dendritic field complexity. Treatment of explants with BDNF+CNTF significantly attenuated dendritic field degeneration. CONCLUSIONS: Retinal explant culture of Thy1-YFP tissue provides a useful model for time-lapse imaging of RGC dendritic field degeneration over a course of several days, and is capable of detecting neuroprotective amelioration of dendritic pruning within individual RGCs. PMID- 26811146 TI - Comparative Analysis of the Endogenous Peptidomes Displayed by HLA-B*27 and Mamu B*08: Two MHC Class I Alleles Associated with Elite Control of HIV/SIV Infection. AB - Indian rhesus macaques are arguably the most reliable animal models in AIDS research. In this species the MHC class I allele Mamu-B*08, among others, is associated with elite control of SIV replication. A similar scenario is observed in humans where the expression of HLA-B*27 or HLA-B*57 has been linked to slow or no progression to AIDS after HIV infection. Despite having large differences in their primary structure, it has been reported that HLA-B*27 and Mamu-B*08 display peptides with sequence similarity. To fine-map the Mamu-B*08 binding motif and assess its similarities with that of HLA-B*27, we affinity purified the peptidomes bound to these MHC class I molecules and analyzed them by LC-MS, identifying several thousands of endogenous ligands. Sequence analysis of both sets of peptides revealed a degree of similarity in their binding motifs, especially at peptide position 2 (P2), where arginine was present in the vast majority of ligands of both allotypes. In addition, several differences emerged from this analysis: (i) ligands displayed by Mamu-B*08 tended to be shorter and to have lower molecular weight, (ii) Mamu-B*08 showed a higher preference for glutamine at P2 as a suboptimal binding motif, and (iii) the second major anchor position, found at POmega, was much more restrictive in Mamu-B*08. In this regard, HLA-B*27 bound efficiently peptides with aliphatic, aromatic (including tyrosine), and basic C-terminal residues while Mamu-B*08 preferred peptides with leucine and phenylalanine in this position. Finally, in silico estimations of binding efficiency and competitive binding assays to Mamu-B*08 of several selected peptides revealed a good correlation between the characterized anchor motif and binding affinity. These results deepen our understanding of the molecular basis of the presentation of peptides by Mamu-B*08 and can contribute to the detection of novel SIV epitopes restricted by this allotype. PMID- 26811148 TI - Predictors of left atrial appendage thrombogenic milieu in patients subjected to transesophageal echocardiography prior to cardioversion of persistent atrial fibrillation. AB - INTRODUCTION: Evidence of left atrial appendage thrombogenic milieu (LAA TM) on transesophageal echocardiography (TEE) is recognized as a surrogate marker for an increased stroke risk. Although the CHA2DS2-VASc scale is commonly used as a measure of thromboembolic risk in patients with atrial fibrillation (AF), it was shown to have only low-to-moderate ability to predict the presence of LAA TM. The potential role of transthoracic echocardiography (TTE) in the refinement of clinical scales for the detection of LAA TM in patients with AF has been readdressed recently. OBJECTIVES: The aim of the study was to identify the predictors of LAA TM among the components of the CHA2DS2-VASc scale and TTE parameters in patients scheduled for electrical cardioversion due to persistent AF. PATIENTS AND METHODS: We conducted a retrospective analysis of demographic, clinical, laboratory, echocardiographic, and medication data of 202 patients (123 men and 79 women; mean age, 65.6 years) with persistent AF, who underwent TEE before electrical cardioversion. RESULTS: Duration of AF exceeding 1 year (odds ratio [OR] = 13.9; P = 0.02), left atrial diameter exceeding 51 mm (OR = 3.98; P = 0.009), left ventricular end-diastolic dimension (LVEDd) exceeding 52 mm (OR = 2.42; P = 0.01), and radiographic evidence of aortic plaques (OR = 2.97; P = 0.007) were shown to be independent predictors of LAA TM in a multivariate regression analysis. CONCLUSIONS: The CHA2DS2-VASc scale did not predict the presence of LAA TM on TEE in patients scheduled for electrical cardioversion due to persistent AF. Of the CHA2DS2-VASc components, only radiographic evidence of aortic plaques, and of TTE parameters, only left atrial enlargement and LVEDd were independent predictors of LAA TM. A comprehensive clinical and echocardiographic assessment of individual risk is indicated in patients before electrical cardioversion due to persistent AF. PMID- 26811147 TI - Unexpected benign histopathology after pancreatoduodenectomy for presumed malignancy: accepting the inevitable. AB - BACKGROUND: Differentiating malignant and benign disease in the pancreatic head and periampullary region is difficult. The aim of this retrospective study was to analyze patients with unexpected "benign" disease after pancreatoduodenectomy (PD) to evaluate the incidence, possible discriminating factors, and outcome. The role of preoperative pathology interpretation in diagnosing malignancy was also assessed. METHODS: Patients with unexpected benign disease were identified from a prospectively maintained database of 446 PDs for presumed malignancy from April 2006 to December 2013. Clinical, radiological, and pathological features were reviewed. Positive predictive values (PPVs) of preoperative pathology interpretation were analyzed. Short-term outcomes were compared. RESULTS: Incidence of unexpected benign disease was 6.5 % (29/446). Radiological diagnostic signs (except the double duct sign) suggestive of malignancy were seen in more than half of the benign cases. Preoperative pathology 'positive' or 'suspicious for malignancy' had a PPV of 97.6 % and 'indeterminate disease' and had a PPV of 90 % for malignancy. 'Benign' or 'negative' pathology had a PPV of 19 % for benign disease in strongly suspected malignancy. There was no significant difference in outcomes in PD for benign versus malignant disease except for a decreased rate of POPFs and a higher trend toward mortality. However, both outcomes were not independently associated with benign disease. CONCLUSIONS: A small percentage of benign disease after PD for "strongly suspected malignancy" is inevitable. No radiological or pathological features can reliably discriminate benign from malignant in these patients. Trend toward higher mortality after PD for unexpected benign disease exists. Detailed preoperative pathological subclassifications are helpful in malignancy. PMID- 26811149 TI - Efficacy of combined administration of intracoronary papaverine plus intravenous adenosine 5'-triphosphate in assessment of fractional flow reserve. AB - BACKGROUND: Inducing maximal coronary hyperemia is important to measure fractional flow reserve (FFR) accurately. Intravenous adenosine and adenosine 5' triphosphate (ATP) have been used to achieve maximal hyperemia. However, they may not induce maximal hyperemia in all patients. The present study evaluated the combined effect of intracoronary papaverine and intravenous ATP on FFR measurements. METHODS: FFR measurements with administration of intracoronary papaverine (12mg in the left coronary artery and 8mg in the right coronary artery), intravenous ATP (140MUg/kg/min), and combined administration of intracoronary papaverine and intravenous ATP were performed in 51 patients with 57 intermediate lesions. RESULTS: The mean FFR after intravenous ATP was higher compared to intracoronary papaverine and intravenous ATP plus intracoronary papaverine (0.76+/-0.13 vs. 0.75+/-0.13 vs. 0.75+/-0.13, p=0.01). FFR-positive lesions (FFR <=0.80) were observed more frequently with intravenous ATP plus intracoronary papaverine compared to intravenous ATP (64.9% vs. 47.4%, p=0.02). Of 32 and 25 FFR-negative lesions with intravenous ATP and intracoronary papaverine, 11 (34%) and 7 (28%) had positive FFR after administration of intravenous ATP plus intracoronary papaverine. No ventricular tachycardia or ventricular fibrillation was observed after administration of intracoronary papaverine. CONCLUSIONS: Maximal hyperemia may not be induced with intravenous ATP in all lesions. When sufficient hyperemia is doubtful during intravenous infusion of ATP, additional intracoronary administration of papaverine may be a possible option. PMID- 26811150 TI - Fecal Immunochemical Test Program Performance Over 4 Rounds of Annual Screening: A Retrospective Cohort Study. AB - BACKGROUND: The fecal immunochemical test (FIT) is a common method for colorectal cancer (CRC) screening, yet its acceptability and performance over several rounds of annual testing are largely unknown. OBJECTIVE: To assess FIT performance characteristics over 4 rounds of annual screening. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Northern and Southern California. PATIENTS: 323 349 health plan members aged 50 to 70 years on their FIT mailing date in 2007 or 2008 who completed the first round of FIT and were followed for up to 4 screening rounds. MEASUREMENTS: Screening participation, FIT positivity (>=20 ug of hemoglobin/g), positive predictive values for adenoma and CRC, and FIT sensitivity for detecting CRC obtained from Kaiser Permanente electronic databases and cancer registries. RESULTS: Of the patients invited for screening, 48.2% participated in round 1. Of those who remained eligible, 75.3% to 86.1% participated in subsequent rounds. Median follow-up was 4.0 years, and 32% of round 1 participants crossed over to endoscopy over 4 screening rounds-7.0% due to a positive FIT result. The FIT positivity rate (5.0%) and positive predictive values (adenoma, 51.5%; CRC, 3.4%) were highest in round 1. Overall, programmatic FIT screening detected 80.4% of patients with CRC diagnosed within 1 year of testing, including 84.5% in round 1 and 73.4% to 78.0% in subsequent rounds. LIMITATION: Screening detection, rather than long-term cancer prevention, was evaluated. CONCLUSION: Annual FIT screening was associated with high sensitivity for CRC, with high adherence to annual follow-up screening among initial participants. The findings indicate that annual programmatic FIT screening is feasible and effective for population-level CRC screening. PRIMARY FUNDING SOURCE: National Institutes of Health. PMID- 26811151 TI - Effects of Aging on Neural Stem/Progenitor Cells and Oligodendrocyte Precursor Cells After Focal Cerebral Ischemia in Spontaneously Hypertensive Rats. AB - Aging and vascular comorbidities such as hypertension comprise critical cofactors that influence how the brain responds to stroke. Ischemic stress induces neurogenesis and oligodendrogenesis in younger brains. However, it remains unclear whether these compensatory mechanisms can be maintained even under pathologically hypertensive and aged states. To clarify the age-related remodeling capacity after stroke under hypertensive conditions, we assessed infarct volume, behavioral outcomes, and surrogate markers of neurogenesis and oligodendrogenesis in acute and subacute phases after transient focal cerebral ischemia in 3- and 12-month-old spontaneously hypertensive rats (SHRs). Hematoxylin and eosin staining showed that 3- and 12-month-old SHRs exhibited similar infarction volumes at both 3 and 14 days after focal cerebral ischemia. However, recovery of behavioral deficits (neurological score assessment and adhesive removal test) was significantly less in 12-month-old SHRs compared to 3 month-old SHRs. Concomitantly, numbers of nestin(+) neural stem/progenitor cells (NSPCs) near the infarct border area or subventricular zone in 12-month-old SHRs were lower than 3-month-old SHRs at day 3. Similarly, numbers of PDGFR-alpha(+) oligodendrocyte precursor cells (OPCs) in the corpus callosum were lower in 12 month-old SHRs at day 3. Lower levels of NSPC and OPC numbers were accompanied by lower expression levels of phosphorylated CREB. By day 14 postischemia, NSPC and OPC numbers in 12-month-old SHRs recovered to similar levels as in 3-month-old SHRs, but the numbers of proliferating NSPCs (Ki-67(+)nestin(+) cells) and proliferating OPCs (Ki-67(+)PDGFR-alpha(+) cells) remained lower in the older brains even at day 14. Taken together, these findings suggest that aging may also decrease poststroke compensatory responses for neurogenesis and oligodendrogenesis even under hypertensive conditions. PMID- 26811154 TI - Extracting DNA words based on the sequence features: non-uniform distribution and integrity. AB - BACKGROUND: DNA sequence can be viewed as an unknown language with words as its functional units. Given that most sequence alignment algorithms such as the motif discovery algorithms depend on the quality of background information about sequences, it is necessary to develop an ab initio algorithm for extracting the "words" based only on the DNA sequences. METHODS: We considered that non-uniform distribution and integrity were two important features of a word, based on which we developed an ab initio algorithm to extract "DNA words" that have potential functional meaning. A Kolmogorov-Smirnov test was used for consistency test of uniform distribution of DNA sequences, and the integrity was judged by the sequence and position alignment. Two random base sequences were adopted as negative control, and an English book was used as positive control to verify our algorithm. We applied our algorithm to the genomes of Saccharomyces cerevisiae and 10 strains of Escherichia coli to show the utility of the methods. RESULTS: The results provide strong evidences that the algorithm is a promising tool for ab initio building a DNA dictionary. CONCLUSIONS: Our method provides a fast way for large scale screening of important DNA elements and offers potential insights into the understanding of a genome. PMID- 26811155 TI - Local Stability of the Trunk in Patients with Degenerative Cerebellar Ataxia During Walking. AB - This study aims to evaluate trunk local stability in a group of patients with degenerative primary cerebellar ataxia and to correlate it with spatio-temporal parameters, clinical variables, and history of falls. Sixteen patients affected by degenerative cerebellar ataxia and 16 gender- and age-matched healthy adults were studied by means of an inertial sensor to measure trunk kinematics and spatio-temporal parameters during over-ground walking. Trunk local dynamic stability was quantified by the maximum Lyapunov exponent with short data series of the acceleration data. According to this index, low values indicate more stable trunk dynamics, while high values denote less stable trunk dynamics. Disease severity was assessed by means of International Cooperative Ataxia Rating Scale (ICARS) according to which higher values correspond to more severe disease, while lower values correspond to less severe disease.Patients displayed a higher short-term maximum Lyapunov exponent than controls in all three spatial planes, which was correlated with the age, onset of the disease, and history of falls. Furthermore, the maximum Lyapunov exponent was negatively correlated with ICARS balance, ICARS posture, and ICARS total scores.These findings indicate that trunk local stability during gait is lower in patients with cerebellar degenerative ataxia than that in healthy controls and that this may increase the risk of falls. Local dynamic stability of the trunk seems to be an important aspect in patients with ataxia and could be a useful tool in the evaluation of rehabilitative and pharmacological treatment outcomes. PMID- 26811156 TI - Prospective analysis of UGT1A1 promoter polymorphism for irinotecan dose escalation in metastatic colorectal cancer patients treated with bevacizumab plus FOLFIRI as the first-line setting: study protocol for a randomized controlled trial. AB - BACKGROUND: Irinotecan is approved and widely administered to metastatic colorectal cancer (mCRC) patients; however, it can cause severe toxicities including neutropenia and diarrhea. The polymorphisms of genes encoding drug metabolizing enzymes can play a crucial role in the increased susceptibility of cancer patients to chemotherapy toxicity. Therefore, we plan to explore the effect of the genetic polymorphism of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) for irinotecan detoxification in mCRC patients. This trial will compare the clinical outcomes and side effects observed in mCRC patients treated with bevacizumab plus 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) with and without UGT1A1 genotyping and irinotecan dose escalation. A total of 400 mCRC patients were randomized into a study group and a control group. METHODS/DESIGN: This trial is a prospective, multicenter, randomized clinical trial comparing UGT1A1 promoter polymorphism for irinotecan dose escalation in mCRC patients administered with bevacizumab plus FOLFIRI as the first-line setting. The enrolled patients were randomly assigned to one of two groups, a study group and a control group, on the basis of receiving UGT1A1 genotyping or not. The study group receive a biweekly FOLFIRI regimen, with irinotecan dose escalation based on UGT1A1 genotyping; whereas the control group receive the conventional biweekly FOLFIRI regimen without UGT1A1 genotyping. The clinicopathological features, response rates, toxicity, and progression-free survival or overall survival will be compared between the two groups. DISCUSSION: Patients with mCRC undergoing UGT1A1 genotyping may receive escalated doses of irinotecan for a potentially more favorable clinical response and outcome, in addition to comparable toxicities. Such personalized medicine based on genotyping may be feasible for clinical practice. TRIAL REGISTRATION: NCT02256800 . Date of registration: 3 October 2014. Date of first patient randomized: 16 January 2015. PMID- 26811157 TI - Percutaneous penetration and pharmacodynamics: Wash-in and wash-off of sunscreen and insect repellent. AB - Increased awareness of skin cancer and mosquito-transmitted diseases has increased use of insect repellents and sunscreens. The challenge in setting recommendations for use and reapplication, especially when used concomitantly, lies in finding the balance between applying a durable product effective in withstanding natural and physical factors such as water, sweat, temperature and abrasion, while limiting percutaneous absorption and decreasing risk of potential dermal and systemic toxicity. Inorganic sunscreens show no or little percutaneous absorption or toxic effects in comparison to organic sunscreens, which show varying levels of dermal penetration and cutaneous adverse effects. An alternative to N,N-diethyl-m-toluamide (DEET), the traditional gold standard compound in insect repellents, picaridin appears as efficacious, has lower risk of toxicity, and when used simultaneously with sunscreen may decrease percutaneous absorption of both compounds. Conversely, combined use of DEET and sunscreen results in significantly higher absorption of both compounds. It is important to increase consumer awareness of "washing in" of various compounds leading to increased risk of toxicity, as well as differences in reapplication need due to "washing off" caused by water, sweat and abrasion. Although much remains to be studied, to maximize efficacy and decrease toxicity, contemporary research tools, including dermatopharmokinetics, should aid these prospective advances. PMID- 26811160 TI - Diagnostic Accuracy of Tissue Doppler Index E/e' for Evaluating Left Ventricular Filling Pressure and Diastolic Dysfunction/Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Tissue Doppler index E/e' is used clinically and in multidisciplinary research for estimation of left ventricular filling pressure (LVFP) and diastolic dysfunction (DD)/heart failure with preserved ejection fraction (HFpEF). Its diagnostic accuracy is not well studied. METHODS AND RESULTS: From the PubMed, Scopus, Embase, and Cochrane databases, we identified 24 studies reporting E/e' and invasive LVFP in preserved EF (>=50%). In random-effects models, E/e' had poor to mediocre linear correlation with LVFP. Summary sensitivity and specificity (with 95% CIs) for the American Society of Echocardiography recommended E/e' cutoffs (lateral, mean, and septal, respectively) to identify elevated LVFP was estimated by using hierarchical summary receiver operating characteristic analysis. Summary sensitivity was 30% (9-48%), 37% (13-61%), and 24% (6-46%), and summary specificity was 92% (82-100%), 91% (80-99%), and 98% (92 100%). Positive likelihood ratio (LR+) was <5 for lateral and mean E/e'. LR+ was slightly >10 for septal E/e' obtained from 4 studies (cumulative sample size <220). For excluding elevated LVFP, summary sensitivity for E/e' (lateral, mean, and septal, respectively) was 64% (38-86%), 36% (3-74%), and 50% (14-81%), while summary specificity was 73% (54-89%), 83% (49-100%), and 89% (66-100%). Because of data set limitations, meaningful inference for identifying HFpEF by using E/e' could not be drawn. With the use of quality assessment tool for diagnostic accuracy studies (Quality Assessment of Diagnostic Accuracy Studies questionnaire), we found substantial risks of bias and/or applicability. CONCLUSIONS: There is insufficient evidence to support that E/e' can reliably estimate LVFP in preserved EF. The diagnostic accuracy of E/e' to identify/exclude elevated LVFP and DD/HFpEF is limited and requires further validation in a well-designed prospective clinical trial. PMID- 26811161 TI - Increased Peripheral Arterial Calcification in Patients Receiving Warfarin. AB - BACKGROUND: Matrix Gla protein is a vitamin K-dependent inhibitor of vascular calcification. Warfarin use is associated with increased breast arterial calcification, but whether this is reflective of other arteries or occurs in men is unclear. In this study, the prevalence of calcification in peripheral arteries was compared in patients with and without warfarin therapy. METHODS AND RESULTS: This retrospective matched cohort study assessed 430 patients with radiographs performed during or after warfarin therapy who were identified by a computerized search of medical records. Each patient was matched to a patient without warfarin exposure based on age, sex, and diabetes status. Patients with warfarin exposure <1 month, history of end-stage renal disease, or serum creatinine >2.0 mg/dl were excluded. Radiographs were reviewed visually for arterial calcification. The prevalence of arterial calcification was 44% greater in patients with versus without warfarin use (30.2% versus 20.9%, P=0.0023) but not on radiographs performed before warfarin therapy (26.4% versus 22.4%, n=156) or prior to 5 years of warfarin therapy. The increase was noted only in the ankle and foot, was limited to a medial pattern of calcification, and was similar in men and women. CONCLUSIONS: Warfarin use is associated with lower extremity arterial calcification in both men and women independent of age, sex, diabetes status, and other patient characteristics. This may have implications for the choice of therapies for long-term anticoagulation. PMID- 26811163 TI - How Reliable are Patient-Reported Rehospitalizations? Implications for the Design of Future Practical Clinical Studies. AB - BACKGROUND: Longitudinal clinical investigations often rely on patient reports to screen for postdischarge adverse outcomes events, yet few studies have examined the accuracy of such patient reports. METHODS AND RESULTS: Patients with acute myocardial infarction (MI) in the TRANSLATE-ACS study were asked during structured interviews at 6 weeks, 6 months, and 12 months postdischarge to report any rehospitalizations. The accuracy of patient-reported rehospitalizations within 1 year of postdischarge was determined using claims-based medical bill validation as the reference standard. The cumulative incidence of rehospitalizations was compared when identified by patient report versus medical bills. Patients were categorized by the accuracy in reporting events (accurate, under-, or over- reporters) and characteristics were compared between groups. Among 10 643 MI patients, 4565 (43%) reported 7734 rehospitalizations. The sensitivity and positive predictive value of patient-reported rehospitalizations were low at 67% and 59%, respectively. A higher cumulative incidence of rehospitalization was observed when identified by patient report versus medical bills (43% vs 37%; P<0.001). Overall, 18% of patients over-reported and 10% under reported the number of hospitalizations. Compared with accurate reporters, under reporters were more likely to be older, female, African American, unemployed, or a non-high-school graduate, and had greater prevalence of clinical comorbidities such as diabetes and past cardiovascular disease. CONCLUSIONS: The accuracy of patient-reported rehospitalizations was low with patients both under- and over reporting events. Longitudinal clinical research studies need additional mechanisms beyond patient report to accurately identify rehospitalization events. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT01088503. PMID- 26811159 TI - Clinical Phenotypes in Heart Failure With Preserved Ejection Fraction. PMID- 26811162 TI - Radial Artery Occlusion After Transradial Interventions: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Radial artery occlusion (RAO) may occur posttransradial intervention and limits the radial artery as a future access site, thus precluding its use as an arterial conduit. In this study, we investigate the incidence and factors influencing the RAO in the current literature. METHODS AND RESULTS: We searched MEDLINE and EMBASE for studies of RAO in transradial access. Relevant studies were identified and data were extracted. Data were synthesized by meta-analysis, quantitative pooling, graphical representation, or by narrative synthesis. A total of 66 studies with 31 345 participants were included in the analysis. Incident RAO ranged between <1% and 33% and varied with timing of assessment of radial artery patency (incidence of RAO within 24 hours was 7.7%, which decreased to 5.5% at >1 week follow-up). The most efficacious measure in reducing RAO was higher dose of heparin, because lower doses of heparin were associated with increased RAO (risk ratio 0.36, 95% CI 0.17-0.76), whereas shorter compression times also reduced RAO (risk ratio 0.28, 95% CI 0.05-1.50). Several factors were found to be associated with RAO including age, sex, sheath size, and diameter of radial artery, but these factors were not consistent across all studies. CONCLUSIONS: RAO is a common complication of transradial access. Maintenance of radial patency should be an integral part of all procedures undertaken through the radial approach. High-dose heparin along with shorter compression times and patent hemostasis is recommended in reducing RAO. PMID- 26811164 TI - Novel Bloodless Potassium Determination Using a Signal-Processed Single-Lead ECG. AB - BACKGROUND: Hyper- and hypokalemia are clinically silent, common in patients with renal or cardiac disease, and are life threatening. A noninvasive, unobtrusive, blood-free method for tracking potassium would be an important clinical advance. METHODS AND RESULTS: Two groups of hemodialysis patients (development group, n=26; validation group, n=19) underwent high-resolution digital ECG recordings and had 2 to 3 blood tests during dialysis. Using advanced signal processing, we developed a personalized regression model for each patient to noninvasively calculate potassium values during the second and third dialysis sessions using only the processed single-channel ECG. In addition, by analyzing the entire development group's first-visit data, we created a global model for all patients that was validated against subsequent sessions in the development group and in a separate validation group. This global model sought to predict potassium, based on the T wave characteristics, with no blood tests required. For the personalized model, we successfully calculated potassium values with an absolute error of 0.36+/-0.34 mmol/L (or 10% of the measured blood potassium). For the global model, potassium prediction was also accurate, with an absolute error of 0.44+/ 0.47 mmol/L for the training group (or 11% of the measured blood potassium) and 0.5+/-0.42 for the validation set (or 12% of the measured blood potassium). CONCLUSIONS: The signal-processed ECG derived from a single lead can be used to calculate potassium values with clinically meaningful resolution using a strategy that requires no blood tests. This enables a cost-effective, noninvasive, unobtrusive strategy for potassium assessment that can be used during remote monitoring. PMID- 26811165 TI - Comprehensive Assessment of Coronary Plaque Progression With Advanced Intravascular Imaging, Physiological Measures, and Wall Shear Stress: A Pilot Double-Blinded Randomized Controlled Clinical Trial of Nebivolol Versus Atenolol in Nonobstructive Coronary Artery Disease. AB - BACKGROUND: We hypothesized that nebivolol, a beta-blocker with nitric oxide mediated activity, compared with atenolol, a beta-blocker without such activity, would decrease oxidative stress and improve the effects of endothelial dysfunction and wall shear stress (WSS), thereby reducing atherosclerosis progression and vulnerability in patients with nonobstructive coronary artery disease. METHODS AND RESULTS: In this pilot double-blinded randomized controlled trial, 24 patients treated for 1 year with nebivolol 10 mg versus atenolol 100 mg plus standard medical therapy underwent baseline and follow-up coronary angiography with assessments of inflammatory and oxidative stress biomarkers, microvascular function, endothelial function, and virtual histology intravascular ultrasound. WSS was calculated from computational fluid dynamics. Virtual histology intravascular ultrasound segments were assessed for vessel volumetrics and remodeling. There was a trend toward more low-WSS segments in the nebivolol cohort (P=0.06). Low-WSS regions were associated with greater plaque progression (P<0.0001) and constrictive remodeling (P=0.04); conversely, high-WSS segments demonstrated plaque regression and excessive expansive remodeling. Nebivolol patients had decreased lumen and vessel areas along with increased plaque area, resulting in more constrictive remodeling (P=0.002). There were no significant differences in biomarker levels, microvascular function, endothelial function, or number of thin-capped fibroatheromas per vessel. Importantly, after adjusting for beta-blocker, low-WSS segments remained significantly associated with lumen loss and plaque progression. CONCLUSION: Nebivolol, compared with atenolol, was associated with greater plaque progression and constrictive remodeling, likely driven by more low-WSS segments in the nebivolol arm. Both beta-blockers had similar effects on oxidative stress, microvascular function, and endothelial function. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov/. Unique identifier: NCT01230892. PMID- 26811166 TI - Effects of Diet Composition and Insulin Resistance Status on Plasma Lipid Levels in a Weight Loss Intervention in Women. AB - BACKGROUND: Optimal macronutrient distribution of weight loss diets has not been established. The distribution of energy from carbohydrate and fat has been observed to promote differential plasma lipid responses in previous weight loss studies, and insulin resistance status may interact with diet composition and affect weight loss and lipid responses. METHODS AND RESULTS: Overweight and obese women (n=245) were enrolled in a 1-year behavioral weight loss intervention and randomly assigned to 1 of 3 study groups: a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut-rich, higher fat (35% energy), lower carbohydrate (45% energy) diet. Blood samples and data available from 213 women at baseline and at 6 months were the focus of this analysis. Triglycerides, total cholesterol, and high- and low-density lipoprotein cholesterol were quantified and compared between and within groups. Triglycerides decreased in all study arms at 6 months (P<0.05). The walnut-rich diet increased high-density lipoprotein cholesterol more than either the lower fat or lower carbohydrate diet (P<0.05). The walnut-rich diet also reduced low-density lipoprotein cholesterol in insulin sensitive women, whereas the lower fat diet reduced both total cholesterol and high-density lipoprotein cholesterol in insulin-sensitive women (P<0.05). Insulin sensitivity and C-reactive protein levels also improved. CONCLUSIONS: Weight loss was similar across the diet groups, although insulin-sensitive women lost more weight with a lower fat, higher carbohydrate diet versus a higher fat, lower carbohydrate diet. The walnut-rich, higher fat diet resulted in the most favorable changes in lipid levels. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01424007. PMID- 26811167 TI - Total Thrombus-Formation Analysis System (T-TAS) Can Predict Periprocedural Bleeding Events in Patients Undergoing Catheter Ablation for Atrial Fibrillation. AB - BACKGROUND: Non-vitamin K antagonist oral anticoagulants are used to prevent thromboembolism in patients with atrial fibrillation. The T-TAS "Total Thrombus formation Analysis System" (Fujimori Kogyo Co Ltd) was developed for quantitative analysis of thrombus formation using microchips with thrombogenic surfaces (collagen, platelet chip [PL] ; collagen plus tissue factor, atheroma chip [AR]). We evaluated the utility of T-TAS in predicting periprocedural bleeding in atrial fibrillation patients undergoing catheter ablation (CA). METHODS AND RESULTS: After exclusion of 20 from 148 consecutive patients undergoing CA, the remaining 128 patients were divided into 2 treatment groups: the warfarin group (n=30) and the non-vitamin K antagonist oral anticoagulants group (n=98). Blood samples obtained on the day of CA (anticoagulant-free point) and at 3 and 30 days after CA were used in T-TAS to compute the thrombus formation area under the curve (AUC; AUC for the first 10 minutes for PL tested at flow rate of 24 MUL/min [PL24 AUC10]; AUC for the first 30 minutes for AR tested at flow rate of 10 MUL/min [AR10-AUC30]). AR10-AUC30 and PL24-AUC10 levels were similar in the 2 groups on the day of CA. Levels of AR10-AUC30, but not PL24-AUC10, were significantly lower in the 2 groups at days 3 and 30 after CA. Multiple logistic regression analyses identified the AR10-AUC30 level on the day of CA as a significant predictor of periprocedural bleeding events (odds ratio 5.7; 95% CI 1.54-21.1; P=0.009). Receiver operating characteristic analysis showed that the AR10-AUC30 level on the day of CA significantly predicted periprocedural bleeding events (AUC 0.859, 95% CI 0.766-0.951; P<0.001). The cutoff AR10-AUC30 level was 1648 for identification of periprocedural bleeding events. CONCLUSIONS: These results suggested that the AR10-AUC30 level determined by T-TAS is a potentially useful marker for prediction of bleeding events in atrial fibrillation patients undergoing CA. PMID- 26811168 TI - Pretreatment of Cardiac Stem Cells With Exosomes Derived From Mesenchymal Stem Cells Enhances Myocardial Repair. AB - BACKGROUND: Exosomes derived from mesenchymal stem cells (MSCs) were proved to boost cell proliferation and angiogenic potency. We explored whether cardiac stem cells (CSCs) preconditioned with MSC exosomes could survive and function better in a myocardial infarction model. METHODS AND RESULTS: DiI-labeled exosomes were internalized with CSCs. They stimulated proliferation, migration, and angiotube formation of CSCs in a dose-dependent manner. In a rat myocardial infarction model, MSC exosome-preconditioned CSCs had significantly better survival, enhanced capillary density, reduced cardiac fibrosis, and restored long-term cardiac function. MicroRNA profiling analysis revealed that a set of microRNAs were significantly changed in CSCs after MSC exosome treatment. CONCLUSIONS: Pretreatment of CSCs with MSC exosomes provided a promising strategy to improve survival and angiogenic potency of CSCs. PMID- 26811169 TI - An Integrated Management Approach to Atrial Fibrillation. AB - BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia resulting in mortality and morbidity. Gaps in oral anticoagulation and education of patients regarding AF have been identified as areas that require improvement. METHODS AND RESULTS: A before-and-after study of 433 patients with newly diagnosed AF in the 3 emergency departments in Nova Scotia from January 1, 2011 until January 31, 2014 was performed. The "before" phase underwent the usual care pathway for AF management; the "after" phase was enrolled in a nurse-run, physician-supervised AF clinic. The primary outcome was a composite of death, cardiovascular hospitalization, and AF-related emergency department visits. A propensity analysis was performed to account for differences in baseline characteristics. RESULTS: A total of 185 patients were enrolled into the usual care group, and 228 patients were enrolled in the AF clinic group. The mean age was 64+/-15 years and 44% were women. In a propensity-matched analysis, the primary outcome occurred in 44 (26.2%) patients in the usual-care group and 29 (17.3%) patients in the AF clinic group (odds ratio 0.71; 95% CI [0.59, 1]; P=0.049) at 12 months. Prescription of oral anticoagulation was increased in the CHADS2 >=2 group (88.4% in the AF clinic versus 58.5% in the usual-care group, P<0.01). CONCLUSIONS: Adoption of this integrated management approach for the burgeoning population of AF may provide an overall benefit to cardiovascular morbidity and mortality. PMID- 26811170 TI - A Model of Supervisor Decision-Making in the Accommodation of Workers with Low Back Pain. AB - Purpose To explore supervisors' perspectives and decision-making processes in the accommodation of back injured workers. Methods Twenty-three semi-structured, in depth interviews were conducted with supervisors from eleven Canadian organizations about their role in providing job accommodations. Supervisors were identified through an on-line survey and interviews were recorded, transcribed and entered into NVivo software. The initial analyses identified common units of meaning, which were used to develop a coding guide. Interviews were coded, and a model of supervisor decision-making was developed based on the themes, categories and connecting ideas identified in the data. Results The decision-making model includes a process element that is described as iterative "trial and error" decision-making. Medical restrictions are compared to job demands, employee abilities and available alternatives. A feasible modification is identified through brainstorming and then implemented by the supervisor. Resources used for brainstorming include information, supervisor experience and autonomy, and organizational supports. The model also incorporates the experience of accommodation as a job demand that causes strain for the supervisor. Accommodation demands affect the supervisor's attitude, brainstorming and monitoring effort, and communication with returning employees. Resources and demands have a combined effect on accommodation decision complexity, which in turn affects the quality of the accommodation option selected. If the employee is unable to complete the tasks or is reinjured during the accommodation, the decision cycle repeats. More frequent iteration through the trial and error process reduces the likelihood of return to work success. Conclusion A series of propositions is developed to illustrate the relationships among categories in the model. The model and propositions show: (a) the iterative, problem solving nature of the RTW process; (b) decision resources necessary for accommodation planning, and PMID- 26811171 TI - Process Evaluation of a Workplace Integrated Care Intervention for Workers with Rheumatoid Arthritis. AB - Purpose To perform a process evaluation of the implementation of a workplace integrated care intervention for workers with rheumatoid arthritis to maintain and improve work productivity. The intervention consisted of integrated care and a participatory workplace intervention with the aim to make adaptations at the workplace. Methods The implementation of the workplace integrated care intervention was evaluated with the framework of Linnan and Steckler. We used the concepts recruitment, reach, dose delivered, dose received, fidelity and satisfaction with the intervention. Data collection occurred through patient questionnaires and medical records. Results Participants were recruited by sending a letter including a reply card from their own rheumatologist. In total, we invited 1973 patients to participate. We received 1184 reply cards, and of these, 150 patients eventually participated in the study. Integrated care was delivered according to protocol for 46.7 %, while the participatory workplace intervention was delivered for 80.6 %. Dose received was nearly 70 %, which means that participants implemented 70 % of the workplace adaptations proposed during the participatory workplace intervention. The fidelity score for both integrated care and the participatory workplace intervention was sufficient, although communication between members of the multidisciplinary team was limited. Participants were generally satisfied with the intervention. Conclusions This process evaluation shows that our intervention was not entirely implemented as intended. The integrated care was not delivered to enough participants, but for the intervention components that were delivered, the fidelity was good. Communication between members of the multidisciplinary team was limited. However, the participatory workplace intervention was implemented successfully, and participants indicated that they were satisfied with the intervention. PMID- 26811172 TI - Process Evaluation of a Participatory Supportive Return to Work Program for Workers Without a Permanent Employment Contract, Sick-Listed Due to a Common Mental Disorder. AB - Purpose This study aimed to perform a process evaluation of a participatory supportive return to work program for workers without a (permanent) employment contract, sick-listed due to a common mental disorder. The program consisted of a participatory approach, integrated care and direct placement in a competitive job. Our main questions were: were these components realized in practice and in accordance with the protocol? The evaluation took place alongside a randomized controlled trial. Methods The study population consisted of workers who filed a sickness benefit claim at the Dutch Social Security Agency, professionals of this agency and of vocational rehabilitation agencies. We focused on sick-listed workers and professionals who had actually participated in the intervention. Data was collected mainly by questionnaires. Results Only 36 out of 94 intervention group participants started with the program. In half of these cases application of integrated care was reported. Most other steps in the program were completed. However, fidelity to the protocol was low to reasonable. Much delay was observed in the execution of the program and only two sick-listed workers were placed in a competitive job. Still, satisfaction with the participatory approach was good. Conclusions Despite the positive evaluation of the participatory approach, the full program was executed less successfully compared to similar programs evaluated in earlier studies. This will probably affect the outcomes of our trial. Findings from this study will help to interpret these outcomes. Nevertheless, more knowledge is needed about experiences of stakeholders who participated in the program. Trial Registration NTR3563. PMID- 26811174 TI - (31)P CSI of the human brain in healthy subjects and tumor patients at 9.4 T with a three-layered multi-nuclear coil: initial results. AB - OBJECTIVE: Investigation of the feasibility and performance of phosphorus ((31)P) magnetic resonance spectroscopic imaging (MRSI) at 9.4 T with a three-layered phosphorus/proton coil in human normal brain tissue and tumor. MATERIALS AND METHODS: A multi-channel (31)P coil was designed to enable MRSI of the entire human brain. The performance of the coil was evaluated by means of electromagnetic field simulations and actual measurements. A 3D chemical shift imaging approach with a variable repetition time and flip angle was used to increase the achievable signal-to-noise ratio of the acquired (31)P spectra. The impact of the resulting k-space modulation was investigated by simulations. Three tumor patients and three healthy volunteers were scanned and differences between spectra from healthy and cancerous tissue were evaluated qualitatively. RESULTS: The high sensitivity provided by the 27-channel (31)P coil allowed acquiring CSI data in 22 min with a nominal voxel size of 15 * 15 * 15 mm(3). Shimming and anatomical localization could be performed with the integrated four-channel proton dipole array. The amplitudes of the phosphodiesters and phosphoethanolamine appeared reduced in tumorous tissue for all three patients. A neutral or slightly alkaline pH was measured within the brain lesions. CONCLUSION: These initial results demonstrate that (31)P 3D CSI is feasible at 9.4 T and could be performed successfully in healthy subjects and tumor patients in under 30 min. PMID- 26811175 TI - New Year's resolution: increase the impact factor of this journal. PMID- 26811173 TI - A review of heart chamber segmentation for structural and functional analysis using cardiac magnetic resonance imaging. AB - Cardiovascular magnetic resonance (CMR) has become a key imaging modality in clinical cardiology practice due to its unique capabilities for non-invasive imaging of the cardiac chambers and great vessels. A wide range of CMR sequences have been developed to assess various aspects of cardiac structure and function, and significant advances have also been made in terms of imaging quality and acquisition times. A lot of research has been dedicated to the development of global and regional quantitative CMR indices that help the distinction between health and pathology. The goal of this review paper is to discuss the structural and functional CMR indices that have been proposed thus far for clinical assessment of the cardiac chambers. We include indices definitions, the requirements for the calculations, exemplar applications in cardiovascular diseases, and the corresponding normal ranges. Furthermore, we review the most recent state-of-the art techniques for the automatic segmentation of the cardiac boundaries, which are necessary for the calculation of the CMR indices. Finally, we provide a detailed discussion of the existing literature and of the future challenges that need to be addressed to enable a more robust and comprehensive assessment of the cardiac chambers in clinical practice. PMID- 26811176 TI - A survey of new oncology drug approvals in the USA from 2010 to 2015: a focus on optimal dose and related postmarketing activities. AB - The maximally tolerated dose (MTD) of cytotoxic agents has historical precedence in treating cancer, as it was believed that dose and therapeutic effect are intrinsically linked and that the MTD would provide greatest therapeutic value. With molecularly targeted agents, the premise of preventing toxicity to normal tissues while modulating tumor growth provides a potential for an increased therapeutic window. Results from these targeted agents suggest we are entering an era of chronic cancer management, which will require design of regimens with long term tolerability. A corresponding switch from MTD-based (toxicity-driven) dosing strategies to alternative paradigms is also expected. The challenge with these targeted agents is to fully understand the complex relationship between pharmacokinetics, pharmacodynamics, and safety and efficacy in early-stage trials, so that the optimal dose and schedule for registration trials may be identified. This review provides a systematic survey of the applications submitted to the United States Food and Drug Administration (FDA) for oncology indications, from 2010 through early 2015, and summarizes the dose selection rationale for registrational trials, the relationship of the MTD to outcomes of the final label dose, the postmarketing requirements or commitments related to dose optimization activities, the role of biomarkers, and typical exposure response modeling methods. PMID- 26811178 TI - A randomized phase II trial of ERCC1 and RRM1 mRNA expression-based chemotherapy versus docetaxel/carboplatin in advanced non-small cell lung cancer. AB - OBJECTIVES: To evaluate whether the selection of first-line chemotherapy based on ERCC1 and RRM1 mRNA expression levels would improve clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: Eligible patients were randomly assigned 1:1 to the experimental and control arms; the experimental arm received gemcitabine/carboplatin (GC) if ERCC1 and RRM1 expression was low, gemcitabine/vinorelbine (GV) if ERCC1 was high and RRM1 was low, docetaxel/carboplatin (DC) if ERCC1 was low and RRM1 was high, and docetaxel/vinorelbine (DV) if both were high. In the control arm, patients received DC. RESULTS: This study was prematurely terminated after the futility analysis of 43 progression-free survival (PFS) events. A total of 55 patients (n = 26 in the experimental arm, n = 29 in the control arm) were evaluable for efficacy and toxicity. Nineteen (73.1%) patients were assigned to receive GC, 0 (0.0%) to GV, 4 (15.4%) to DC, and 3 (11.5%) to DV in the experimental arm. The overall response rates were 42.3 and 48.3% in the experimental and control arms, respectively, which were not statistically different (P = 0.657). The median PFS was 5.2 months in the experimental arm and 5.4 months in the control arm (P = 0.286). The median overall survival was 17.4 months in the experimental arm and 12.6 months in the control arm (P = 0.638). The occurrence of grade 3 or higher neutropenia (69.2 vs. 93.1%, P = 0.035) and febrile neutropenia (3.8 vs. 24.1%, P = 0.054) was more common in the control arm. CONCLUSION: ERCC1 and RRM1 mRNA expression-based chemotherapy did not improve clinical outcomes in advanced NSCLC (NCT01648517). PMID- 26811177 TI - Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs. AB - The presence of a microenvironment within most tumours containing regions of low oxygen tension or hypoxia has profound biological and therapeutic implications. Tumour hypoxia is known to promote the development of an aggressive phenotype, resistance to both chemotherapy and radiotherapy and is strongly associated with poor clinical outcome. Paradoxically, it is recognised as a high-priority target and one of the therapeutic strategies designed to eradicate hypoxic cells in tumours is a group of compounds known collectively as hypoxia-activated prodrugs (HAPs) or bioreductive drugs. These drugs are inactive prodrugs that require enzymatic activation (typically by 1 or 2 electron oxidoreductases) to generate cytotoxic species with selectivity for hypoxic cells being determined by (1) the ability of oxygen to either reverse or inhibit the activation process and (2) the presence of elevated expression of oxidoreductases in tumours. The concepts underpinning HAP development were established over 40 years ago and have been refined over the years to produce a new generation of HAPs that are under preclinical and clinical development. The purpose of this article is to describe current progress in the development of HAPs focusing on the mechanisms of action, preclinical properties and clinical progress of leading examples. PMID- 26811179 TI - ASP9853, an inhibitor of inducible nitric oxide synthase dimerization, in combination with docetaxel: preclinical investigation and a Phase I study in advanced solid tumors. AB - PURPOSE: ASP9853 is an inhibitor of inducible nitric oxide (NO) synthase (iNOS) dimerization, which results in decreased NO production. Here, we report preclinical pharmacology of ASP9853 and the impact of ASP9853 in combination with a taxane on tumor volume in vivo. In addition, a Phase I open-label study of ASP9853 plus docetaxel was conducted to assess this combination in patients with advanced solid tumors. METHODS: The preclinical efficacy of ASP9853 in combination with a taxane was studied in tumor-bearing mice. In the clinic, patients with solid tumors that had progressed or failed to respond to previous therapies were treated with once-daily ASP9853 in combination with docetaxel once every 3 weeks to assess safety and tolerability and to determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D) of the combination. RESULTS: ASP9853 in combination with docetaxel showed greater tumor growth inhibition than docetaxel alone against non-small lung cancer xenografts. Twenty patients were treated with ASP9853 and docetaxel. Five patients experienced neutropenic dose-limiting toxicities. Owing to overall toxicity that limited further dose escalation, the ASP9853 concentrations predicted for efficacy, based on the preclinical data, were not achieved. Due to toxicity and lack of clear efficacy, the study was terminated without determination of MTD or RP2D. CONCLUSIONS: Inhibition of iNOS by ASP9853 in combination with docetaxel was not tolerable and resulted in the possible potentiation of neutropenia. Manipulation of the iNOS pathway, with or without chemotherapy, appears to be more complicated than initially expected. PMID- 26811180 TI - Photoinhibition and photoinhibition-like damage to the photosynthetic apparatus in tobacco leaves induced by pseudomonas syringae pv. Tabaci under light and dark conditions. AB - BACKGROUND: Pseudomonas syringae pv. tabaci (Pst), which is the pathogen responsible for tobacco wildfire disease, has received considerable attention in recent years. The objective of this study was to clarify the responses of photosystem I (PSI) and photosystem II (PSII) to Pst infection in tobacco leaves. RESULTS: The net photosynthetic rate (Pn) and carboxylation efficiency (CE) were inhibited by Pst infection. The normalized relative variable fluorescence at the K step (W k) and the relative variable fluorescence at the J step (V J) increased while the maximal quantum yield of PSII (F v/F m) and the density of Q A-reducing PSII reaction centers per cross section (RC/CSm) decreased, indicating that the reaction centers, and the donor and acceptor sides of PSII were all severely damaged after Pst infection. The PSI activity decreased as the infection progressed. Furthermore, we observed a considerable overall degradation of PsbO, D1, PsaA proteins and an over-accumulation of reactive oxygen species (ROS). CONCLUSIONS: Photoinhibition and photoinhibition-like damage were observed under light and dark conditions, respectively, after Pst infection of tobacco leaves. The damage was greater in the dark. ROS over-accumulation was not the primary cause of the photoinhibition and photoinhibition-like damage. The PsbO, D1 and PsaA proteins appear to be the targets during Pst infection under light and dark conditions. PMID- 26811181 TI - Escherichia coli biofilm: development and therapeutic strategies. AB - Escherichia coli biofilm consists of a bacterial colony embedded in a matrix of extracellular polymeric substances (EPS) which protects the microbes from adverse environmental conditions and results in infection. Besides being the major causative agent for recurrent urinary tract infections, E. coli biofilm is also responsible for indwelling medical device-related infectivity. The cell-to-cell communication within the biofilm occurs due to quorum sensors that can modulate the key biochemical players enabling the bacteria to proliferate and intensify the resultant infections. The diversity in structural components of biofilm gets compounded due to the development of antibiotic resistance, hampering its eradication. Conventionally used antimicrobial agents have a restricted range of cellular targets and limited efficacy on biofilms. This emphasizes the need to explore the alternate therapeuticals like anti-adhesion compounds, phytochemicals, nanomaterials for effective drug delivery to restrict the growth of biofilm. The current review focuses on various aspects of E. coli biofilm development and the possible therapeutic approaches for prevention and treatment of biofilm-related infections. PMID- 26811182 TI - Quality of life in caregivers with and without chronic disease: Welsh Health Survey, 2013. AB - Background: The aim of the present study was to investigate and compare quality of life after regular care provision in people with and without currently treated chronic disease in a country-wide and population-based setting. Methods: Data were retrieved from Welsh Health Survey, 2013. Information on demographics, lifestyle factors, health conditions, regular care provision and quality of life was obtained by household interview. Chi-square test, t-test and survey-weighted multi-nominal regression modelling were performed. Results: Of 15 007 Welsh adults aged 16 and above, 2751 (19.1%) people reported that they have been giving care for any sick, disabled or frail person. They tended to be aged 40-74, being female, education 25, physically active, current smokers and living in second-hand smoking households. In caregivers with current chronic disease (n = 1562), they have experienced physical health limits, bodily pains, emotional problems, less calm and less cheerful. In caregivers without current chronic diseases (n = 1151), they have experienced physical health limits, bodily pains, less cheerful, downhearted and unhappiness. Conclusions: This is the first study to examine quality of life in caregivers both with and without currently treated chronic disease. Longitudinal monitoring and increasing education, training and support to lessen caregiving burden would be suggested. PMID- 26811184 TI - Associations between neighbourhood environmental factors and the uptake and effectiveness of a brief intervention to increase physical activity: findings from deprived urban communities in an English city. AB - Background: Evidence suggests behavioural interventions may exacerbate health inequalities, potentially due to differences in uptake or effectiveness. We used a physical activity intervention targeting deprived communities to identify neighbourhood-level factors that might explain differences in programme impact. Methods: Individuals aged 40-65 were sent a postal invitation offering a brief intervention to increase physical activity. We used postcodes linkage to determine whether neighbourhood indicators of deprivation, housing, crime and proximity to green spaces and leisure facilities predicted uptake of the initial invitation or an increase in physical activity level in those receiving the brief intervention. Results: A total of 4134 (6.8%) individuals responded to the initial invitation and of those receiving the intervention and contactable after 3 months, 486 (51.6%) reported an increase in physical activity. Area deprivation scores linked to postcodes predicted intervention uptake, but not intervention effectiveness. Neighbourhood indicators did not predict either uptake or intervention effectiveness. Conclusions: The main barrier to using brief intervention invitations to increase physical activity in deprived, middle-aged populations was the low uptake of an intervention requiring significant time and motivation from participants. Once individuals have taken up the intervention offer, neighbourhood characteristics did not appear to be significant barriers to successful lifestyle change. PMID- 26811185 TI - Response to Letter From Ruan and Bumgarner: Breakthrough Pain Associated With a Reduction in Serum Buprenorphine Concentration During Dialysis. PMID- 26811186 TI - Second-Line Nilotinib Treatment in Patients With Chronic Myeloid Leukemia in a Developing Country. PMID- 26811188 TI - S-1-based regimens and the risk of leucopenic complications; a Meta-analysis with comparison to other fluoropyrimidines and non fluoropyrimidines. AB - BACKGROUND: We performed a meta-analysis oriented at the risk of leucopenic complications associated with S-1-based regimens. PATIENTS AND METHODS: The studies that were granted eligibility for inclusion include randomized phase II and III trials of patients with solid tumors on S-1; that entailed details of events of febrile neutropenia, all-grade and high-grade neutropenia and leucopenia. RESULTS: After rejecting ineligible studies, a total of 28 clinical trials were elected eligible for further quantitative analysis. The RR of febrile neutropenia, all-grade and high-grade neutropenia for S-1 vs.non fluoropyrimidine controls was 0.27 [95% CI 0.16, 0.46; P < 0.0001] 0.69 [95% CI 0.58, 0.81; P < 0.00001] and 0.47 [95% CI 0.32, 0.70; P = 0.0002], correspondingly; while The RR of all-grade and high-grade leucopenia for S-1 vs.non fluoropyrimidine controls was 0.60 [95% CI 0.46, 0.79; P = 0.0002] and 0.34 [95% CI 0.14, 0.79; P = 0.01], respectively. CONCLUSIONS: The risk of febrile neutropenia, all-grade and high grade neutropenia and leucopenia is less in S-1-based therapy than in non fluoropyrimidine regimens; yet comparable to the risk associated with infusional 5FU or capecitabine-based regimens. PMID- 26811189 TI - Pre-surgical regional blocks in orthognathic surgery: prospective study evaluating their influence on the intraoperative use of anaesthetics and blood pressure control. AB - In orthognathic surgery, maxillary (CNV2) and mandibular (CNV3) divisions of the trigeminal nerve can be blocked successfully prior to surgery. In this study, it was hypothesized that regional blocks (nerve block over a particular region: bilateral CNV2 and CNV3 divisions of the trigeminal nerve) would decrease the total requirement for intraoperative anaesthetic agents and facilitate the process of hypotensive anaesthesia. Local anaesthesia containing 1/100,000 epinephrine and 10ml 0.5% levobupivacaine was injected into the planned incisions in 50 patients. Twenty-five patients (group A) underwent orthognathic surgery without regional blocks and another 25 patients (group B) underwent surgery with regional blocks. The anaesthetic protocol was the same in both groups and administered by a single anaesthesiologist. The mean arterial pressure was recorded at several points throughout the operation, as well as all the medications used. The blood loss and the amounts of medications administered were lower in group B than in group A. In patients receiving regional blocks, the amounts of fentanyl and nicardipine required were significantly lower. The use of pre-emptive anaesthesia in orthognathic surgery may reduce the overall amounts of medications required for hypotensive anaesthesia, facilitate the intraoperative control of blood pressure, and decrease intraoperative blood loss. PMID- 26811192 TI - Get control of your commas. PMID- 26811190 TI - Root Type-Specific Reprogramming of Maize Pericycle Transcriptomes by Local High Nitrate Results in Disparate Lateral Root Branching Patterns. AB - The adaptability of root system architecture to unevenly distributed mineral nutrients in soil is a key determinant of plant performance. The molecular mechanisms underlying nitrate dependent plasticity of lateral root branching across the different root types of maize are only poorly understood. In this study, detailed morphological and anatomical analyses together with cell type specific transcriptome profiling experiments combining laser capture microdissection with RNA-seq were performed to unravel the molecular signatures of lateral root formation in primary, seminal, crown, and brace roots of maize (Zea mays) upon local high nitrate stimulation. The four maize root types displayed divergent branching patterns of lateral roots upon local high nitrate stimulation. In particular, brace roots displayed an exceptional architectural plasticity compared to other root types. Transcriptome profiling revealed root type-specific transcriptomic reprogramming of pericycle cells upon local high nitrate stimulation. The alteration of the transcriptomic landscape of brace root pericycle cells in response to local high nitrate stimulation was most significant. Root type-specific transcriptome diversity in response to local high nitrate highlighted differences in the functional adaptability and systemic shoot nitrogen starvation response during development. Integration of morphological, anatomical, and transcriptomic data resulted in a framework underscoring similarity and diversity among root types grown in heterogeneous nitrate environments. PMID- 26811191 TI - Acylsugar Acylhydrolases: Carboxylesterase-Catalyzed Hydrolysis of Acylsugars in Tomato Trichomes. AB - Glandular trichomes of cultivated tomato (Solanum lycopersicum) and many other species throughout the Solanaceae produce and secrete mixtures of sugar esters (acylsugars) on the plant aerial surfaces. In wild and cultivated tomato, these metabolites consist of a sugar backbone, typically glucose or sucrose, and two to five acyl chains esterified to various positions on the sugar core. The aliphatic acyl chains vary in length and branching and are transferred to the sugar by a series of reactions catalyzed by acylsugar acyltransferases. A phenotypic screen of a set of S. lycopersicum M82 * Solanum pennellii LA0716 introgression lines identified a dominant genetic locus on chromosome 5 from the wild relative that affected total acylsugar levels. Genetic mapping revealed that the reduction in acylsugar levels was consistent with the presence and increased expression of two S. pennellii genes (Sopen05g030120 and Sopen05g030130) encoding putative carboxylesterase enzymes of the alpha/beta-hydrolase superfamily. These two enzymes, named ACYLSUGAR ACYLHYDROLASE1 (ASH1) and ASH2, were shown to remove acyl chains from specific positions of certain types of acylsugars in vitro. A survey of related genes in M82 and LA0716 identified another trichome-expressed ASH gene on chromosome 9 (M82, Solyc09g075710; LA0716, Sopen09g030520) encoding a protein with similar activity. Characterization of the in vitro activities of the SpASH enzymes showed reduced activities with acylsugars produced by LA0716, presumably contributing to the high-level production of acylsugars in the presence of highly expressed SpASH genes. PMID- 26811193 TI - A novel mentorship programme for residents integrating academic development, clinical teaching and graduate medical education assessment. AB - INTRODUCTION: Mentorship fosters career development and growth. During residency training, mentorship should support clinical development along with intellectual and academic interests. Reported resident mentoring programmes do not typically include clinical components. We designed a programme that combines academic development with clinical feedback and assessment in a four-year emergency medicine residency programme. METHODS: Incoming interns were assigned an advisor. At the conclusion of the intern year, residents actively participated in selecting a mentor for the duration of residency. The programme consisted of quarterly meetings, direct clinical observation and specific competency assessment, assistance with lecture preparation, real-time feedback on presentations, simulation coaching sessions, and discussions related to career development. Faculty participation was recognized as a valuable component of the annual review process. Residents were surveyed about the overall programme and individual components. RESULTS: Over 88 % of the respondents said that the programme was valuable and should be continued. Senior residents most valued the quarterly meetings and presentation help and feedback. Junior residents strongly valued the clinical observation and simulation sessions. CONCLUSIONS: A comprehensive mentorship programme integrating clinical, professional and academic development provides residents individualized feedback and coaching and is valued by trainees. Individualized assessment of clinical competencies can be conducted through such a programme. PMID- 26811194 TI - Epidemiology and trend of common cancers in Iran (2004-2008). AB - BACKGROUND: Cancer is one of the most important causes of mortality worldwide. It includes approximately 13% of death cases. This study aimed to investigate the incidence trend of common cancers in Iran during 2004-2008 to improve reporting distribution the disease. METHODS: This was a retrospective study. The study population was all cases of cancer diagnosed in Iran during 2004-2008. The crude incidence rate of cancers was calculated per 100 000 people by age groups and sex. Age-standardised incidence rates (ASRs) were calculated using direct standardisation and the world standard population. Data were analysed using SPSS (version 17) and Microsoft Office Excel 2007. RESULTS: In this study, a total of 301 055 cases of cancer were diagnosed. ASRs were 60.51 and 84.51 in women and men respectively. Most common cancers in men were skin (ASR = 18.85), stomach (15.02), bladder (ASR = 11.25), prostate (ASR = 8.93) and colorectal (ASR = 8.29). Most common cancers in women were breast (ASR = 18.24), skin (ASR = 12.01), colorectal (ASR = 7.75), stomach (ASR = 7.05) and haematocyte (ASR = 4.01). CONCLUSION: A significant increase was observed in the incidence of cancers in the country. Therefore, it is necessary to perform screening, early diagnosis and treatment in early stages of cancers. PMID- 26811196 TI - Impact of maternal physical activity on fetal breathing and body movement--A review. AB - Fetal movements, which include body and breathing movement, are important indicators of fetal well-being and nervous system development. These have been shown to be affected by intrauterine conditions. While maternal physical activity does induce a change in intrauterine conditions and physiology, its impact on fetal movements is still unclear. This paper will provide a brief review of the literature and outline the current knowledge with regards to the effects of maternal exercise on fetal body and breathing movements. PMID- 26811195 TI - Targeted next-generation sequencing of 22 mismatch repair genes identifies Lynch syndrome families. AB - Causative germline mutations in mismatch repair (MMR) genes can only be identified in ~50% of families with a clinical diagnosis of the inherited colorectal cancer (CRC) syndrome hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome (LS). Identification of these patients are critical as they are at substantially increased risk of developing multiple primary tumors, mainly colorectal and endometrial cancer (EC), occurring at a young age. This demonstrates the need to develop new and/or more thorough mutation detection approaches. Next-generation sequencing (NGS) was used to screen 22 genes involved in the DNA MMR pathway in constitutional DNA from 14 HNPCC and 12 sporadic EC patients, plus 2 positive controls. Several softwares were used for analysis and functional annotation. We identified 5 exonic indel variants, 42 exonic nonsynonymous single-nucleotide variants (SNVs) and 1 intronic variant of significance. Three of these variants were class 5 (pathogenic) or class 4 (likely pathogenic), 5 were class 3 (uncertain clinical relevance) and 40 were classified as variants of unknown clinical significance. In conclusion, we have identified two LS families from the sporadic EC patients, one without a family history of cancer, supporting the notion for universal MMR screening of EC patients. In addition, we have detected three novel class 3 variants in EC cases. We have, in addition discovered a polygenic interaction which is the most likely cause of cancer development in a HNPCC patient that could explain previous inconsistent results reported on an intronic EXO1 variant. PMID- 26811197 TI - The interval between carotid artery stenting and open heart surgery is related to perioperative complications. AB - OBJECTIVES: To assess 30-day outcomes and the optimal interval between carotid artery stenting (CAS) and open heart surgery (OHS). BACKGROUND: Whether or not they show symptoms of carotid atherosclerosis, patients with significant carotid stenosis who underwent OHS face a high risk of perioperative stroke. Planning appropriate treatment for carotid stenosis before OHS has become an important clinical issue. METHODS: From January 2005 to June 2010, 154 inpatients scheduled for CAS and OHS were recruited and followed up for 30 days after OHS. The primary end point was a composite of major stroke or neurological death. The secondary end points included a composite of major stroke, myocardial infarction (MI) or any death, minor stroke, and acute kidney injury (AKI). RESULTS: The incidence of the primary end point, the composite of major stroke, MI or any death, minor stroke and AKI was 3.2%, 5.8%, 2.6%, and 4.5%, respectively. Only an interval between CAS and OHS of <=5 days could independently predict the incidence of the primary end point (OR, 14.06, 95% CI, 1.52-130.13; P=0.020). Moreover, congestive heart failure (OR, 7.07, 95% CI, 1.55-21.27; P=0.012) and an interval between CAS and OHS of <=5 days (OR, 7.05, 95% CI, 1.58-31.40; P=0.010) were identified as independent risk factors for the composite of major stroke, MI, or any death. CONCLUSIONS: Our findings indicate that CAS followed by OHS is safe and feasible. More importantly, an interval between CAS and OHS of >5 days may decrease periprocedural complications, especially major stroke and neurological death. PMID- 26811199 TI - Toward More Robust Inferential Procedures for Coefficient Alpha Under Sampling of Both Subjects and Conditions. AB - Barchard and Hakstian (1997b) demonstrated that inferential procedures used with coefficient alpha are not robust under sampling of both subjects and conditions (Type 12 sampling) with measurement data departing from essentially-parallel form. In the first of 2 studies reported here, a sample-based, non-analytical degrees-of-freedom correction factor was empirically developed that correlated almost perfectly with the independently-established correct degrees of freedom for the data. In the second study, application of this correction factor was assessed through a comprehensive simulation study involving Type 12 data sets representing a wide range of design characteristics and manifesting tau equivalent measurement. Use of the correction factor yielded actual Type I error rates closer to nominal values than were obtained using uncorrected inferential procedures. Implications for practice and future research are discussed. PMID- 26811198 TI - Signaling mechanism underlying the histamine-modulated action of hypoglossal motoneurons. AB - Histamine, an important modulator of the arousal states of the central nervous system, has been reported to contribute an excitatory drive at the hypoglossal motor nucleus to the genioglossus (GG) muscle, which is involved in the pathogenesis of obstructive sleep apnea. However, the effect of histamine on hypoglossal motoneurons (HMNs) and the underlying signaling mechanisms have remained elusive. Here, whole-cell patch-clamp recordings were conducted using neonatal rat brain sections, which showed that histamine excited HMNs with an inward current under voltage-clamp and a depolarization membrane potential under current-clamp via histamine H1 receptors (H1Rs). The phospholipase C inhibitor U 73122 blocked H1Rs-mediated excitatory effects, but protein kinase A inhibitor and protein kinase C inhibitor did not, indicating that the signal transduction cascades underlying the excitatory action of histamine on HMNs were H1R/Gq/11 /phospholipase C/inositol-1,4,5-trisphosphate (IP3). The effects of histamine were also dependent on extracellular Na(+) and intracellular Ca(2+), which took place via activation of Na(+)-Ca(2+) exchangers. These results identify the signaling molecules associated with the regulatory effect of histamine on HMNs. The findings of this study may provide new insights into therapeutic approaches in obstructive sleep apnea. We proposed the post-synaptic mechanisms underlying the modulation effect of histamine on hypoglossal motoneuron. Histamine activates the H1Rs via PLC and IP3, increases Ca(2+) releases from intracellular stores, promotes Na(+) influx and Ca(2+) efflux via the NCXs, and then produces an inward current and depolarizes the neurons. Histamine modulates the excitability of HMNs with other neuromodulators, such as noradrenaline, serotonin and orexin. We think that these findings should provide an important new direction for drug development for the treatment of obstructive sleep apnea. PMID- 26811200 TI - A Regression Equation for Determining the Dimensionality of Data. AB - Parallel analysis has received much support and attention as a criterion for using eigenvalues to determine the dimensionality of data. Parallel analysis compares sample eigenvalues to expected eigenvalues of a sample from a correlation matrix generated by independent normally distributed random variables. To make parallel analysis more accessible to researchers, several studies have proposed multiple regression equations for estimating the expected value of the eigenvalues of a sample correlation matrix assuming that the population correlation matrix is the identity matrix. A new regression equation to estimate the mean value of eigenvalues is presented in this article and a comparative study reveals favorable performance of this proposed equation to previously published regression equations. This proposed technique has the advantage that a table of coefficients, listing regression coefficients for each eigenvalue root, is not needed. PMID- 26811201 TI - Linear Confirmatory Factor Models to Evaluate Multitrait-Multimethod Matrices: The Effects of Number of Indicators and Correlation Among Methods. AB - Two models for confirmatory factor analysis of multitrait-multimethod data (MTMM) were assessed, the correlated traits-correlated methods (CTCM), and the correlated traits-correlated uniqueness models (CTCU). Two Monte Carlo experiments (100 replications per cell) were performed to study the behavior of these models in terms of magnitude and direction of bias, and accuracy of estimates. Study one included a single indicator per trait-method combination, and it manipulated three independent variables: matrix type, from three traits three methods to six traits-six methods; correlation among method factors, from zero to .6; and model type (CTCM and CTCU). Study two included simulated MTMM matrices with two or more indicators per trait-method combination. Again, three independent variables were manipulated: number of indicators per trait-method combination, from 2 to 5; correlation among methods; and model type, CTCM and CTCU. The results from study one showed that the CTCU model performed very well for MTMM designs with a single indicator per trait-method combination, and consistently better than the CTCM model. However, the results from study two showed that the CTCM model worked reasonably well and better than the CTCU model when more than two indicators per trait-method combination were available. Despite the CTCM model's allowance for correlation between methods, results pointed to better estimates when methods were orthogonal. The main conclusion of the present article is that the use of CTCU models in the situations described in study one and the use of CTCM models in those represented in study two could be recommended. PMID- 26811202 TI - Review of MPLUS. PMID- 26811203 TI - Multidimensional Measurement from Dynamic Tests: Abstract Reasoning Under Stress. AB - Dynamic testing has been popularized as an alternative procedure to measuring ability. Traditionally, ability is measured from performance on problem-solving tasks that depend heavily on prior knowledge or developed skills. In contrast, ability measured from dynamic tests depends on the responsiveness of an examinee to varying testing conditions. If the varying conditions are cues or instruction, it is often maintained that the dynamic test provides a direct measure of learning ability. This article focused on computerized dynamic testing, in which cues and items are presented according to objective algorithms. Both appropriate designs and psychometric models for dynamic testing are elaborated. Further, two studies are presented that support the psychometric properties of a test that measures the susceptibility of reasoning to stressors. PMID- 26811204 TI - Using Multilevel Logistic Regression to Evaluate Person-Fit in IRT Models. AB - I describe how multilevel logistic regression can be used to assess the consistency of an individual's response pattern with an item response theory measurement model. Specifically, by treating item responses as being nested within individuals, multilevel logistic regression is used to estimate a person response curve that models how an individual's item endorsement rate decreases as a function of item difficulty. The slope of an individual's person-response curve is used as an indicator of the degree of response consistency or person-fit. I argue that the proposed multilevel modeling approach to person-fit assessment has several potential advantages over traditional techniques. The most important advantage being that the multilevel modeling approach allows explanatory variables to be entered into the model so that the causes of response inconsistency or differential test functioning can be investigated. PMID- 26811205 TI - Synthetic Polyamines to Regulate mRNA Translation through the Preservative Binding of Eukaryotic Initiation Factor 4E to the Cap Structure. AB - Polyion complexes (PICs) of mRNA with synthetic polyamines are receiving increasing attention as mRNA delivery vehicles, and the search for polyamine structure maximizing the translational efficiency of complexed mRNA becomes a critical research topic. Herein, we discovered that fine-tuning of the protonation status of synthetic polyamines can regulate mRNA translation through the preservative binding of eukaryotic initiation factor 4E to m(7)GpppN (cap structure) on the 5' end of mRNA. A series of polyamines with varied numbers of aminoethylene repeats in their side chains were prepared by an aminolysis reaction of poly(beta-benzyl-l-aspartate) and paired with mRNA to form PICs. PICs formed from polyamines with higher numbers of aminoethylene repeats preserved the original translational efficiency to naked mRNA, whereas the efficiency significantly dropped by decreasing the number of aminoethylene repeats in the polyamines. Immunoprecipitation assays using anti-eIF4E antibodies revealed that the binding affinity of eIF4E to the cap structure of mRNA in the PIC was sensitive to the number of charged aminoethylene repeats in the polyamine side chain and was strongly correlated with their translational efficiency. These results indicate that the fine-tuning of the polyamine structure plays a critical role in maximizing the translational efficiency of mRNA in the PICs having potential utility as mRNA delivery vehicles. PMID- 26811206 TI - Sperm concentration and forward motility are not correlated with age in adolescents with an idiopathic varicocele and symmetrical testicular volumes. AB - AIM: Idiopathic varicocele is a common condition that may impair fertility. Its treatment in children and adolescents is reserved for those patients who develop symptoms or testicular growth arrest. We evaluated the trends in sperm parameters among adolescent varicocele patients with symmetrical testicular volumes who have not undergone varicocelectomy. METHOD: Data were prospectively collected from a single institution (2009 to 2014). Post-pubertal patients aged 12 to 17years produced semen samples by masturbation. Outcomes measured were semen volume, sperm concentration, and forward motility. Additional variables recorded included: a) testicular volume (ultrasound measurement), b) clinical varicocele grade, c) venous Doppler grading. Linear regression analysis was performed using Fisher's transformation. P<0.05 was considered significant, and data are presented as median (IQ range). RESULTS: Forty-one patients with a median age of 15.4 (15.0-15.9) years each provided a sperm sample during the study period. Thirty-five had grade 3 (visible) varicocele, and 6 had grade 2 (palpable) varicocele. All patients had spontaneous venous reflux on Doppler ultrasound, and none had undergone varicocelectomy prior to producing the sperm sample. Table 1 summarizes the sperm parameters according to patient age. The overall median sperm concentration was 37 (16-64) millions/ml and was not correlated with age. The overall median forward motility was 55% (44-64) and was not correlated with age. Thirty-four patients had normal sperm parameters, which remained within the WHO range of normality. CONCLUSIONS: Following the European Association of Urology guidelines does not cause progressive deterioration of sperm parameters between the age of 12 and 17years. PMID- 26811207 TI - Lin28 and let-7 in the Metabolic Physiology of Aging. AB - The Lin28/let-7 molecular switch has emerged as a central regulator of growth signaling pathways and metabolic enzymes. Initially discovered to regulate developmental timing in the nematode, the Lin28/let-7 pathway of RNA regulation has gained prominence for its role in mammalian stem cells, cancer cells, tissue development, and aging. By regulating RNAs, the pathway coordinates cellular growth and cellular metabolism to influence metabolic physiology. Here, we review this regulatory mechanism and its impact on cancers, which reactivate Lin28, cardiovascular diseases, which implicate let-7, human genome-wide association studies (GWAS) of growth, and metabolic diseases, which implicate the Lin28/let-7 pathway. We also highlight questions relating to Barker's Hypothesis and the potential actions of the Lin28/let-7 pathway on programming long-lasting epigenetic effects. PMID- 26811208 TI - Lineage Reprogramming: A Promising Road for Pancreatic beta Cell Regeneration. AB - Cell replacement therapy is a promising method to restore pancreatic beta cell function and cure diabetes. Distantly related cells (fibroblasts, keratinocytes, and muscle cells) and developmentally related cells (hepatocytes, gastrointestinal, and pancreatic exocrine cells) have been successfully reprogrammed into beta cells in vitro and in vivo. However, while some reprogrammed beta cells bear similarities to bona fide beta cells, others do not develop into fully functional beta cells. Here we review various strategies currently used for beta cell reprogramming, including ectopic expression of specific transcription factors associated with islet development, repression of maintenance factors of host cells, regulation of epigenetic modifications, and microenvironmental changes. Development of simple and efficient reprogramming methods is a key priority for developing fully functional beta cells suitable for cell replacement therapy. PMID- 26811209 TI - High dose rate brachytherapy for prostate cancer: Standard of care and future direction. AB - High dose rate brachytherapy is a highly conformal method of radiation dose escalation for prostate cancer and one of several treatment options for men with localised disease. The large doses per fraction exploit the low alpha/beta ratio of prostate cancer cells so that biological radiation dose delivered is substantially greater than that achieved with conventional external beam delivery. This review article presents contemporary data on the rationale for high dose rate brachytherapy including treatment technique and future directions. PMID- 26811211 TI - Characterization of novel isobenzofuranones by DFT calculations and 2D NMR analysis. AB - Phthalides are frequently found in naturally occurring substances and exhibit a broad spectrum of biological activities. In the search for compounds with insecticidal activity, phthalides have been used as versatile building blocks for the syntheses of novel potential agrochemicals. In our work, the Diels-Alder reaction between furan-2(5H)-one and cyclopentadiene was used successfully to obtain (3aR,4S,7R,7aS)-3a,4,7,7a-tetrahydro-4,7-methanoisobenzofuran-1(3H)-one and (3aS,4R,7S,7aR)-3a,4,7,7a-tetrahydro-4,7-methanoisobenzofuran-1(3H)-one (2) and (3aS,4S,7R,7aR)-3a,4,7,7a-tetrahydro-4,7-methanoisobenzofuran-1(3H)-one and (3aR,4R,7S,7aS)-3a,4,7,7a-tetrahydro-4,7-methanoisobenzofuran-1(3H)-one (3). The endo adduct (2) was brominated to afford (3aR,4R,5R,7R,7aS,8R)-5,8 dibromohexahydro-4,7-methanoisobenzofuran-1(3H)-one and (3aS,4S,5S,7S,7aR,8S)-5,8 dibromohexahydro-4,7-methanoisobenzofuran-1(3H)-one (4) and (3aS,4R,5R,6S,7S,7aR) 5,6-dibromohexahydro-4,7-methanoisobenzofuran-1(3H)-one and (3aR,4S,5S,6R,7R,7aS) 5,6-dibromohexahydro-4,7-methanoisobenzofuran-1(3H)-one (5). Following the initial analysis of the NMR spectra and the proposed two novel unforeseen products, we have decided to fully analyze the classical and non-classical assay structures with the aid of computational calculations. Computation to predict the (13) C and (1) H chemical shifts for mean absolute error analyses have been carried out by gauge-including atomic orbital method at M06-2X/6-31+G(d,p) and B3LYP/6-311+G(2d,p) levels of theory for all viable conformers. Characterization of the novel unforeseen compounds (4) and (5) were not possible by employing only the experimental NMR data; however, a more conclusive structural identification was performed by comparing the experimental and theoretical (1) H and (13) C chemical shifts by mean absolute error and DP4 probability analyses. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26811212 TI - Use of tranexamic acid in combat casualties. Experience of the Spanish medical corps. Clinical series and literature review. AB - OBJECTIVE: To describe the experience with tranexamic acid (TXA) during the care of combat causalities treated in the Spanish military hospital based in Herat (Afghanistan) and to perform an analysis of the literature related to the military setting. MATERIAL AND METHODS: With the approval of the appropriate military institutions, an analysis was performed on the use of TXA in combat casualties treated between March and May 2014. Of the 745 patients seen, 10 were due to a firearm/explosive device (combat casualties). A descriptive analysis was performed on the data collected. Absolute and relative frequencies (%) were used for the categorical variables. For central tendency measurements, the arithmetic mean and standard deviation or the median and interquartile range was calculated. The data were obtained from the military records of patients treated in the Herat military hospital. RESULTS: All the patients in this series received TXA within the first 3 hours after the attack. The most frequent dose used was one gram i.v, with bleeding was controlled in 100% of cases. All the patients survived and none of them had secondary effects. These data agree with that recommended in the combat casualties treatment guide followed by military health in other countries in this setting. CONCLUSION: All combat casualties were treated with TXA within the first 3 hours. The most frequent dose used was one gram iv and bleeding was controlled in all cases. All the patients survived with no adverse effects being observed. PMID- 26811213 TI - Medical care for refugees: A question of ethics and public health. PMID- 26811214 TI - Sclerosing mesenteritis: A real manifestation or histological mimic of IgG4 related disease? AB - We present three cases of sclerosing mesenteritis and review the literature to learn whether or not sclerosing mesenteritis is an IgG4-related disease (IgG4 RD). Our patients were all adult males. Their mesenteric masses ranged from 6.5 to 14.5 cm in the greatest diameter. Tissue specimens showed moderate to severe lymphoplasmacytic infiltration with occasional eosinophils against a background of irregular fibrosis. Both obliterative phlebitis and storiform fibrosis were noted in all cases. IgG4+ plasma cells were moderately increased in number (46 to 85 cells/high-power field). However, unlike IgG4-RD, the IgG4+/IgG+ plasma cell ratio was <40% (28% to 35%). Serum IgG4 concentrations were also within the normal range (43.2 to 105 mg/dL; normal range <135 mg/dL). Two biopsy cases showed spontaneous regression on imaging approximately 5 months later. No sclerosing conditions were found in other organs. The literature review identified 11 additional cases of sclerosing mesenteritis with IgG4+ plasma cell infiltration. However, conclusive cases with four characteristic features (high serum IgG4 levels, tissue IgG4 elevation, multi-organ involvement, and effective response to glucocorticoid therapy) have never been reported. In conclusion, although sclerosing mesenteritis shares histological features with IgG4-RD, most cases are less likely to be IgG4-related. IgG4-RD seemingly seldom, if ever, affects this anatomical site. PMID- 26811215 TI - Nitrogen-rich 4,4'-azo bis(1,2,4-triazolone) salts--the synthesis and promising properties of a new family of high-density insensitive materials. AB - 4,4'-Azo-bis(1,2,4-triazolone) (ZTO) based salts from alkaline (Li(+), K(+), Na(+), and Cs(+)), alkaline earth metal salts (Mg(2+), Ca(2+), Sr(2+), and Ba(2+)) and hydrazinium salt were synthesized in a simple, straightforward manner and were characterized by IR and NMR spectroscopy, elemental analysis. The single crystal X-ray diffraction of seven salts (Na(+), K(+), Cs(+), Mg(2+), Ca(2+), Sr(2+), Ba(2+), and N2H5(+)) are also reported. The X-ray structures show that in the title compounds, the metal atoms are bonded to the nitrogen and oxygen atoms in the bistetrazole ring to form a sandwich structure. In addition, the thermal stabilities of all the title compounds were determined using thermogravimetric differential thermal analysis (TG-DTA). All these new materials exhibit excellent thermal stability, high density, acceptable detonation properties, and excellent insensitivity to impact (h50 > 60 cm). In particular, the barium, caesium and strontium salts are of great interest as potential high-density insensitive materials. PMID- 26811216 TI - THE DELINKING OF SEX AND MARRIAGE: PATHWAYS TO FERTILITY AMONG YOUNG FILIPINO WOMEN. AB - Partnership and fertility patterns of young Filipinos have changed dramatically from previous generations, with a widening gap between sexual initiation and marriage, and concurrent increases in teenage pregnancy and unwanted fertility. Further understanding of young adults' social contexts and partnership patterns are needed to inform reproductive health programmes and policies affecting young Filipinos. Multivariate Poisson regression models were conducted with longitudinal and inter-generational data from the Cebu Longitudinal Health and Nutrition Survey (1998-2009) to examine the predictors of young women's fertility. Age at first sex, and number and duration of partnerships each independently and significantly predicted women's fertility by 2009 after controlling for contextual influences. Young women with more conservative attitudes towards dating, sex and marriage, and who perceived their mothers to have more conservative attitudes, had higher fertility than their peers, as did young women with mothers who reported more adolescent sexual behaviours. In contrast, fertility was lower among daughters who had higher levels of communication with their mothers. Given high levels of unintended fertility and teenage pregnancy in the Philippines, the findings indicate that the interval between sexual initiation and first and subsequent partnerships may be ideal intervention points for reproductive health services for young Filipinos. PMID- 26811217 TI - Regulation and quality evaluation system for HIV diagnostics in China. AB - A sophisticated regulatory framework has been constructed for Human immunodeficiency virus (HIV) diagnostics in China, which have developed over the past 30 years. China National Institutes for Food and Drug Control acts as the legal institution in this regulatory framework, launching important activities to ensure the quality of HIV diagnostics. These include the analysis of the main problems faced in developing domestic HIV diagnostics, by investigating the quality of HIV diagnostics and their development; exploring the key factors affecting the quality of HIV diagnostics, to determine the criteria for screening national reference samples; the development of new technologies and methods for preparing reference samples; and the establishment of nine types of national reference panels and nine national standards to evaluate the quality of HIV diagnostics. Based on these researches, a quality evaluation system was established, including nine types of national reference panels, nine national standards for HIV diagnostics, and five sample banks (HIV-positive sample bank, HIV-negative sample bank, common international genotype sample bank, seroconversion series sample bank, HIV virus bank) to evaluate the quality of HIV diagnostics in China. The regulatory framework and the quality evaluation system are pivotal in ensuring the quality of the HIV diagnostics licensed in China. PMID- 26811218 TI - Porcine parvovirus as a contaminant in cell cultures and laboratory supplies. AB - Although PPV has been described as a cellular contaminant, few recent studies about the presence of this virus in cell cultures, serum, and trypsin were found in the literature. The purpose of this study was to detect the presence of porcine parvovirus (PPV) by polymerase chain reaction (PCR) in cell cultures, serum, and trypsin used in official public laboratories of educational institutes and research centers. We tested samples of cell cultures (88), batches of trypsin (10), and fetal bovine serum (13) from different manufacturers. The PCR for beta actin and GAPDH was used to evaluate the efficiency of DNA extraction from samples. The PPV DNA was detected in 52 of 88 (59.1%) cell culture samples. One in ten batches of trypsin tested for PPV DNA was positive. In no sample of fetal bovine serum, amplification of PPV DNA was observed. Positive samples were tested and confirmed by another analyst. In addition, all positive samples were sequenced. Our results indicate that regular PCR testing for PPV in cell cultures and their supplies is important. PMID- 26811219 TI - Development of flocculent Saccharomyces cerevisiae strain GYK-10 for the selective fermentation of glucose/fructose in sugar mills. AB - Advances in glucose/fructose-selective ethanol production have successfully enhanced raw sugar extraction from sugarcane juice by converting inhibitory substances (i.e., glucose/fructose) into ethanol, which is removed by subsequent operations in cane sugar mills. However, the commercial implementation of this breakthrough process in existing cane sugar mills requires a yeast strain that (i) can be used in food production processes, (ii) exhibits stable saccharometabolic selectivity, and (iii) can be easily separated from the saccharide solution. In this study, we developed a suitable saccharometabolism selective and flocculent strain, Saccharomyces cerevisiae GYK-10. We obtained a suitable yeast strain for selective fermentation in cane sugar mills using a yeast mating system. First, we crossed a haploid strain defective in sucrose utilization with a flocculent haploid strain. Next, we performed tetrad dissection of the resultant hybrid diploid strain and selected GYK-10 from various segregants by investigating the sucrose assimilation and flocculation capacity phenotypes. Ten consecutive fermentation tests of the GYK-10 strain using a bench-scale fermentor confirmed its suitability for the implementation of practical selective fermentation in a commercial sugar mill. The strain exhibited complete saccharometabolic selectivity and sustained flocculation, where it maintained a high ethanol yield and conversion rate throughout the test. PMID- 26811220 TI - Characterization of a trehalose-degrading enzyme from the hyperthermophilic archaeon Sulfolobus acidocaldarius. AB - We purified a cytosolic trehalase (TreH) from a thermoacidophilic archaeon Sulfolobus acidocaldarius. Enzyme activity in cell-free extracts indicated that trehalose degradation in the cell occurred via the hydrolytic activity of TreH, and not via TreP (phosphorolytic activity) or TreT (transfer activity). TreH was purified to near-homogeneity by DEAE anion-exchange chromatography, followed by size exclusion and HiTrap Q anion-exchange chromatography, and its molecular mass was estimated as 40 kDa. Maximum activity was observed at 85 degrees C and pH 4.5. The half-life of TreH was 53 and 41 min at 90 degrees C and 95 degrees C, respectively. TreH was highly specific for trehalose and was inhibited by glucose with a Ki of 0.05 mM. Compared with TreH from other trehalases, TreH from S. acidocaldarius is the most thermostable trehalase reported so far. Furthermore, this is the first trehalase characterized in the Archaea domain. PMID- 26811221 TI - Experimental evolution and gene knockout studies reveal AcrA-mediated isobutanol tolerance in Ralstonia eutropha. AB - Isobutanol (IBT) has attracted much attention from researchers as a next generation drop-in biofuel. Ralstonia eutropha is a gram-negative bacterium which naturally produces polyhydroxybutyrate (PHB), and has been reported to produce IBT after metabolic engineering. Similar to other microbes, R. eutropha experiences toxicity from branched-chain alcohols and is unable to grow in the presence of IBT concentrations higher than 0.5% (v v(-1)). Such low tolerance greatly limits the ability of R. eutropha to grow and produce IBT. In order to study toxicity to the cells, IBT-tolerant strains were developed by experimental evolution, revealing that two genes, previously described as being related to IBT tolerance in Escherichia coli (acrA and acrA6), also presented mutations in R. eutropha evolved strains. The effect on the physiology of the cells of in-frame deletions of each of these genes was assessed in wild type and engineered IBT producing strains in an attempt to reproduce a tolerant phenotype. The mutant strains' ability to tolerate, consume, and produce IBT were also analyzed. Although deletions of acrA6 and acrA did not significantly improve R. eutropha growth in the presence of IBT, these deletions improved cell survival in the presence of high concentrations of IBT in the extracellular milieu. Moreover, an in-frame acrA deletion in an engineered IBT-producing R. eutropha enhanced the strain's ability to produce IBT, which could potentially be associated with enhanced survival at high IBT concentrations. PMID- 26811222 TI - Preparation of Quenchbodies by protein transamination reaction. AB - Quenchbody (Q-body) is an antibody fragment labeled with fluorescent dye(s), which functions as a biosensor via the antigen-dependent removal of the quenching effect on fluorophores. It is based on the principle that the fluorescence of the dye(s) attached to the antibody N-terminal region is quenched primarily by the tryptophan residues present in the variable regions, and this quenching is released when the antigen binds to the antibody, resulting in increased fluorescence intensity. Hence Q-body is utilized in various immunoassays for the rapid and sensitive detection of analytes. So far, Q-bodies have been prepared by using a cell-free translation system or by combining Escherichia coli expression and post-labeling steps. However, the above methods need antibody gene cloning, and are time-consuming. In this study, we report a novel approach to prepare Q bodies by protein N-terminal transamination. We used the antigen-binding fragment (Fab) of an antibody against the bone-Gla-protein (BGP), a biomarker for bone diseases, which was expressed in E. coli. The purified Fab was treated with Rapoport's salt to convert the amino group at the N-terminus to a ketone group, which in turn was allowed to react with fluorescent probes that have aminooxy or hydrazide groups, to prepare a Q-body. The Q-body prepared by this method could detect the BGP-C7 antigen at concentrations as low as 10 nM. Since the approach can label the protein N-terminus directly, it could be applied for preparing Q bodies from natural antibodies and for the rapid screening of high-performance Q bodies. PMID- 26811223 TI - Changes in bacterial community structure in a full-scale membrane bioreactor for municipal wastewater treatment. AB - This study investigated changes in the structure and metabolic capabilities of the bacterial community in a full-scale membrane bioreactor (MBR) treating municipal wastewater. Microbial monitoring was also conducted for a parallel running conventional activated sludge (CAS) process treating the same influent. The mixed-liquor suspended solid concentration in the MBR reached a steady-state on day 73 after the start-up. Then the MBR maintained higher rates of removal of organic compounds and nitrogen than the CAS process did. Terminal restriction fragment length polymorphism analysis revealed that the bacterial community structure in the MBR was similar to that in the CAS process at the start-up, but it became very different from that in the CAS process in the steady state. The bacterial community structure of the MBR continued to change dynamically even after 20 months of the steady-state operation, while that of the CAS process was maintained in a stable condition. By contrast, Biolog assay revealed that the carbon source utilization potential of the MBR resembled that of the CAS process as a whole, although it declined transiently. Overall, the results indicate that the bacterial community of the MBR has flexibility in terms of its phylogenetic structure and metabolic activity to maintain the high wastewater treatment capability. PMID- 26811224 TI - Contrasting Management of Small Cell Lung Cancer and Non-Small Cell Lung Cancer: Emerging Data for Low-Dose Computed Tomography Screening. PMID- 26811225 TI - The 2015 World Health Organization Classification of Tumors of the Pleura: Advances since the 2004 Classification. AB - A new World Health Organization (WHO) Classification of Tumors of the Pleura has recently been published. While the histologic classification of pleural malignant mesothelioma remains the same in the 2015 WHO classification as it was in the 2004 classification, multiple new observations have been recorded. First, more detailed study has been performed of histologic subtyping of epithelioid mesothelioma. In particular, it has been recognized that the pleomorphic subtype is associated with a poor prognosis, similar to that of sarcomatoid malignant mesothelioma. Second, there is improved understanding of the role of immunohistochemistry in distinguishing mesothelioma from carcinomas of various sites. Third, the criteria for distinguishing malignant mesothelioma from reactive mesothelial proliferations has been further refined. Fourth, additional studies of sarcomatoid mesothelioma have defined the frequency and spectrum of various histologic and immunohistochemical features, including heterologous elements. Finally, pleural well-differentiated papillary mesotheliomas are better defined and cases with invasive foci are recognized. In addition, several promising observations in mesothelioma pathology and genetics have been made in the past decade. These are now the subject of further investigation to determine if they can be validated in ways that will significantly impact clinical practice. These include a preliminary study of grading, suggesting that nuclear atypia and mitotic count are independent prognostic markers. The discovery of inactivating mutations in the BRCA1-associated protein 1 gene in sporadic and hereditary mesothelioma has opened up a variety of novel molecular, clinical, and diagnostic investigations. One possible diagnostic application includes the setting of separating mesothelioma from reactive mesothelial proliferations, where it may play a role in conjunction with p16 FISH. Another useful discovery was that the NAB2-STAT6 fusion is characteristic of solitary fibrous tumors. This led to development of a STAT6 antibody that is a reliable immunohistochemical marker for solitary fibrous tumors. Genetic studies also led to the finding that WWTR1-CAMTA1 fusions are useful diagnostic markers for epithelioid hemangioendotheliomas, which can present as pleural-based masses. Finally, desmoid type fibromatosis, a locally aggressive tumor that can present in the pleura, has been shown to frequently have CTNNB1 gene mutations and express beta catenin by immunohistochemistry. PMID- 26811226 TI - Trends in Subpopulations at High Risk for Lung Cancer. AB - INTRODUCTION: Two-thirds of patients in the United States with newly diagnosed lung cancer would not meet the current U.S. Preventive Services Task Force (USPSTF) screening criteria, which suggests a need for amendment of the definition of high risk. To provide evidence of additional high-risk subpopulations and estimated gains and losses from using different criteria for screening eligibility, we conducted a two-step study using three cohorts. METHODS: The two prospective cohorts comprised 5988 patients in whom primary lung cancer was diagnosed between 1997 and 2011 (the hospital cohort) and 850 defined community residents (the community cohort); the retrospective cohort consisted of the population of Olmsted County, Minnesota, which was observed for 28 years (1984-2011). Subgroups of patients with lung cancer who might have been identified using additional determinates were estimated and compared between the community and hospital cohorts. The findings were supported by indirect comparative projections of two ratios: benefit to harm and cost to effectiveness. RESULTS: Former cigarette smokers who had a smoking history of 30 or more pack years and 15 to 30 quit-years and were 55 to 80 years old formed the largest subgroup not meeting the current screening criteria; they constituted 12% of the hospital cohort and 17% of community cohort. Using the expanded criteria suggested by our study may add 19% more CT examinations for detecting 16% more cases when compared with the USPSTF criteria. Meanwhile, the increases in false positive results, overdiagnosis, and radiation-related lung cancer deaths are 0.6%, 0.1%, and 4.0%, respectively. CONCLUSIONS: Current USPSTF screening criteria exclude many patients who are at high risk for development of lung cancer. Including individuals who are younger than 81 years, have a smoking history of 30 or more pack-years, and have quit for 15 to 30 years may significantly increase the number of cases of non-overdiagnosed screen-detected lung cancer, does not significantly add to the number of false-positive cases, and saves more lives with an acceptable amount of elevated exposure to radiation and cost. PMID- 26811227 TI - An Unmet Need in the WHO 2015 Biopsy Classification: Poorly Differentiated NSCCs with Positive Neuroendocrine Markers. PMID- 26811228 TI - Testing for Neuroendocrine Immunohistochemical Markers Should Not Be Performed in Poorly Differentiated NSCCs in the Absence of Neuroendocrine Morphologic Features according to the 2015 WHO Classification. PMID- 26811229 TI - MET Gene Status in Malignant Mesothelioma Using Fluorescent In Situ Hybridization. PMID- 26811230 TI - Estimation of life expectancy, loss-of-life expectancy, and lifetime healthcare expenditures for schizophrenia in Taiwan. AB - By employing a novel semi-parametric extrapolation method, the life expectancies after the first hospitalization for schizophrenia and the associated lifetime healthcare expenditures were both estimated. Based on the linkage between the National Health Insurance Research Database and the National Mortality Registry of Taiwan, we have established a schizophrenic cohort for 2000-2010 and followed up to 2011. Survival function was estimated through Kaplan-Meier's method and extrapolated throughout life. We applied a simple linear regression to the logit transformed survival ratio between the schizophrenic cohort and the sex-, age matched referents via Monte Carlo simulation from the national life table. The monthly survival probability was multiplied by the average healthcare expenditures and summed throughout life to estimate the lifelong cost reimbursed by the National Health Insurance. The results showed that patients diagnosed at age 20-29 had the highest expected years of life lost (EYLL), 15 and 9years, in men and women, respectively, with corresponding lifetime healthcare expenditures of USD 48,000 and 53,000. Males generally had higher health cost per life-year than their female counterparts across their lifespan. We applied the same method to the first 6years of the cohort and extrapolated to 12years, which showed that the relative biases for different age strata were less than 5%. We thus concluded that the semi-parametric extrapolation method might provide a timely estimation of lifetime outcomes for health care planning of schizophrenia. PMID- 26811231 TI - Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey. AB - Patients with schizophrenia have a higher risk of metabolic syndrome (MetS). MetS prevalence varies with ethnicity. Although environmental factors, such as lack of physical activity and unbalanced diet, can lead to MetS, these may differ between outpatients and inpatients with schizophrenia. The Japanese mental health care system differs from that in other countries. However, few studies have investigated the prevalence of MetS in Japanese patients with schizophrenia. Therefore, we conducted a nationwide survey to clarify the prevalence of MetS in Japanese outpatients and inpatients with schizophrenia. We investigated the risk of MetS by questionnaire in 520 facilities for outpatients and 247 facilities for inpatients. There were 7655 outpatients and 15,461 inpatients with schizophrenia. MetS prevalence was based on the National Cholesterol Education Program Adult Treatment Panel III (ATP III-A) and the Japan Society for the Study of Obesity (JASSO). The overall MetS prevalence in outpatients using the ATP III-A definition was 34.2%, with 37.8% in men and 29.4% in women, compared with 13.0% in inpatients, with 12.3% in men and 13.9% in women. MetS prevalence in outpatients was approximately 2- to 3-fold higher than in inpatients. In conclusion, MetS prevalence in Japanese outpatients was approximately 3-fold higher than in inpatients. Therefore, we should pay more attention to the risk of physical disease in Japanese patients with schizophrenia, considering the difference in health characteristics between outpatients and inpatients. PMID- 26811232 TI - Neurocognitive insight and objective cognitive functioning in schizophrenia. AB - Neurocognitive impairment is a core component of schizophrenia affecting everyday functioning; the extent to which individuals with schizophrenia show awareness of neurocognitive impairment (neurocognitive insight) is unclear. This study investigated neurocognitive insight and examined the cross-sectional relationships between neurocognitive insight and objective neurocognition and functional capacity performance in a large outpatient sample. 214 participants with schizophrenia-spectrum disorders completed measures of neurocognition, functional capacity, and self-reported neurocognitive problems. Latent profile analysis classified participants with regard to neuropsychological performance and self-report of neurocognitive problems. The resulting classes were then compared on executive functioning performance, functional capacity performance, and psychiatric symptom severity. More than three quarters of the sample demonstrated objective neurocognitive impairment (global deficit score>=0.50). Among the participants with neurocognitive impairment, 54% were classified as having "impaired" neurocognitive insight (i.e., reporting few neurocognitive problems despite having objective neurocognitive impairment). Participants with impaired vs. intact neurocognitive insight did not differ on executive functioning measures or measures of functional capacity or negative symptom severity, but those with intact neurocognitive insight reported higher levels of positive and depressive symptoms. A substantial portion of individuals with schizophrenia and objectively measured neurocognitive dysfunction appear unaware of their deficits. Patient self-report of neurocognitive problems, therefore, is not likely to reliably assess neurocognition. Difficulty self-identifying neurocognitive impairment appears to be unrelated to executive functioning, negative symptoms, and functional capacity. For those with intact neurocognitive insight, improving depressive and psychotic symptoms may be a valuable target to reduce illness burden. PMID- 26811233 TI - Summaries for Patients. Hematuria as a Marker of Occult Urinary Tract Cancer. PMID- 26811236 TI - Use of an Acetyl Derivative to Improve GC-MS Determination of Norbuprenorphine in the Presence of High Concentrations of Buprenorphine in Urine. AB - Certain patients being treated with SuboxoneTM or SubutexTM can exhibit very high buprenorphine and low norbuprenorphine concentrations in urine. Very high buprenorphine can interfere with buprenorphine-D4 used as an internal standard, causing errors in norbuprenorphine determination by gas chromatography-mass spectrometry (GC-MS). We used a modified method of Wu et al. to introduce norbuprenorphine-D3 as a separate internal standard for norbuprenorphine. This allowed us to accurately measure norbuprenorphine in neat urine specimens when buprenorphine is present in extremely high concentrations. Laboratories measuring buprenorphine and metabolite by GC-MS may face this problem if their clientele includes patients being treated with other medications that interfere with the cytochrome p450 CYP 3A4-mediated conversion of buprenorphine to norbuprenorphine. PMID- 26811237 TI - The History of Infant Formula: Quality, Safety, and Standard Methods. AB - Food-related laws and regulations have existed since ancient times. Egyptian scrolls prescribed the labeling needed for certain foods. In ancient Athens, beer and wines were inspected for purity and soundness, and the Romans had a well organized state food control system to protect consumers from fraud or bad produce. In Europe during the Middle Ages, individual countries passed laws concerning the quality and safety of eggs, sausages, cheese, beer, wine, and bread; some of these laws still exist today. But more modern dietary guidelines and food regulations have their origins in the latter half of the 19th century when the first general food laws were adopted and basic food control systems were implemented to monitor compliance. Around this time, science and food chemistry began to provide the tools to determine "purity" of food based primarily on chemical composition and to determine whether it had been adulterated in any way. Since the key chemical components of mammalian milk were first understood, infant formulas have steadily advanced in complexity as manufacturers attempt to close the compositional gap with human breast milk. To verify these compositional innovations and ensure product quality and safety, infant formula has become one of the most regulated foods in the world. The present paper examines the historical development of nutritional alternatives to breastfeeding, focusing on efforts undertaken to ensure the quality and safety from antiquity to present day. The impact of commercial infant formulas on global regulations is addressed, along with the resulting need for harmonized, fit-for-purpose, voluntary consensus standard methods. PMID- 26811234 TI - Articular cartilage tissue engineering: the role of signaling molecules. AB - Effective early disease modifying options for osteoarthritis remain lacking. Tissue engineering approach to generate cartilage in vitro has emerged as a promising option for articular cartilage repair and regeneration. Signaling molecules and matrix modifying agents, derived from knowledge of cartilage development and homeostasis, have been used as biochemical stimuli toward cartilage tissue engineering and have led to improvements in the functionality of engineered cartilage. Clinical translation of neocartilage faces challenges, such as phenotypic instability of the engineered cartilage, poor integration, inflammation, and catabolic factors in the arthritic environment; these can all contribute to failure of implanted neocartilage. A comprehensive understanding of signaling molecules involved in osteoarthritis pathogenesis and their actions on engineered cartilage will be crucial. Thus, while it is important to continue deriving inspiration from cartilage development and homeostasis, it has become increasingly necessary to incorporate knowledge from osteoarthritis pathogenesis into cartilage tissue engineering. PMID- 26811238 TI - Hemoptysis and lung disease as a manifestation of pulmonary vein stenosis after cryoballoon catheter ablation for atrial fibrillation. PMID- 26811235 TI - Cellular functions of TMEM16/anoctamin. AB - Ca(2+)-activated Cl(-) channels (CaCCs) are a class of Cl(-) channels activated by intracellular Ca(2+) that are known to mediate numerous physiological functions. In 2008, the molecular identity of CaCCs was found to be anoctamin 1 (ANO1/TMEM16A). Its roles have been studied in electrophysiological, histological, and genetic aspects. ANO1 is known to mediate Cl(-) secretion in secretory epithelia such as airways, salivary glands, intestines, renal tubules, and sweat glands. ANO1 is a heat sensor activated by noxious heat in somatosensory neurons and mediates acute pain sensation as well as chronic pain. ANO1 is also observed in vascular as well as airway smooth muscles, controlling vascular tone as well as airway hypersensitivity. ANO1 is upregulated in numerous types of cancers and thus thought to be involved in tumorigenesis. ANO1 is also found in proliferating cells. In addition to ANO1, involvement of its paralogs in pathophysiological conditions was also reported. ANO2 is involved in olfaction, whereas ANO6 works as a scramblase whose mutation causes a rare bleeding disorder, the Scott syndrome. ANO5 is associated with muscle and bone diseases. Recently, an X-ray crystal structure of a fungal TMEM16 was reported, which explains a precise molecular gating mechanism as well as ion conduction or phospholipid transport across the plasma membrane. PMID- 26811239 TI - Genetic variations in regions of bovine and bovine-like enteroviral 5'UTR from cattle, Indian bison and goat feces. AB - BACKGROUND: Bovine enteroviruses (BEV) are members of the genus Enterovirus in the family Picornaviridae. They are predominantly isolated from cattle feces, but also are detected in feces of other animals, including goats and deer. These viruses are found in apparently healthy animals, as well as in animals with clinical signs and several studies reported recently suggest a potential role of BEV in causing disease in animals. In this study, we surveyed the presence of BEV in domestic and wild animals in Thailand, and assessed their genetic variability. METHODS: Viral RNA was extracted from fecal samples of cattle, domestic goats, Indian bison (gaurs), and deer. The 5' untranslated region (5'UTR) was amplified by nested reverse transcription-polymerase chain reaction (RT-PCR) with primers specific to BEV 5'UTR. PCR products were sequenced and analyzed phylogenetically using the neighbor-joining algorithm to observe genetic variations in regions of the bovine and bovine-like enteroviral 5'UTR found in this study. RESULTS: BEV and BEV-like sequences were detected in the fecal samples of cattle (40/60, 67 %), gaurs (3/30, 10 %), and goats (11/46, 24 %). Phylogenetic analyses of the partial 5'UTR sequences indicated that different BEV variants (both EV-E and EV-F species) co-circulated in the domestic cattle, whereas the sequences from gaurs and goats clustered according to the animal species, suggesting that these viruses are host species-specific. CONCLUSIONS: Varieties of BEV and BEV-like 5'UTR sequences were detected in fecal samples from both domestic and wild animals. To our knowledge, this is the first report of the genetic variability of BEV in Thailand. PMID- 26811240 TI - [Not Available]. PMID- 26811241 TI - [Choosing wisely--against overuse in healthcare systems--activities in Germany and Austria in geriatric medicine]. AB - In 2012, the American Board of Internal Medicine (ABIM) Foundation initiated the Choosing Wisely campaign to promote discussion between physicians and patients (or proxies) on decision-making in medicine, and to reduce the use of procedures and therapies which are not necessary, or harmful to patients. The American Geriatrics Society (AGS), the American Medical Directors Association and the Society of Post-Acute and Long-Term Medicine (AMDA) participated in this initiative and both published 10 recommendations on procedures that should be discussed and avoided. Furthermore, some scientific societies have also published recommendations concerning elderly patients. As the campaign attracted considerable international attention, an International Roundtable was established in 2014. In Germany a similar initiative to address overuse and underuse was established by the German Society of Internal Medicine (DGIM) in 2015. The German Society of Geriatrics (DGG) was invited to address subjects affecting elderly patients that are of relevance to the German health care system. As a member of the Commission of the Association of the Scientific Medical Societies in Germany (AWMF), it also participated actively in the development of a methods paper on how to prepare recommendations. The German College of General Practitioners and Family Physicians (DEGAM) has developed a new guideline on this topic and in Austria preliminary activities are already underway. A clear, transparent, structured and evidence-based approach may help avoid some of the methodological weaknesses to be found in the development of the U.S. recommendations. Whereas the U.S. campaign only addresses overuse, the German campaign will also address underuse and misuse. PMID- 26811242 TI - [Sexuality in overweight and obesity]. AB - The association between obesity and sexual dysfunction has been described in many studies. Neurobiological, hormonal, vascular and mental disturbances are the main reasons in male and in female gender. Sexual interest and desire, sexual arousal, orgasm, painful intercourse and premature ejaculation can be involved. Data for prevalence of sexual function disturbances in obese people are scarce and most studies were small. For screening of sexual function we recommend the International Index of Erectile Function (IIEF)-Score, which contains 15 Items for males and the Female Sexual Function Index (FSFI), which contains 19 items for females. Treatment of sexual function disturbances include lifestyle changes with an increase of physical activity, weight control, healthy eating and smoking cessation. Testosterone substitution in cases of real hypogonadism and treatment with PDE-5 inhibitors are well documented treatment options in male individuals. New treatment options for female patients with variable effectiveness are fibanserin, testosterone, bupropione and oxytocin. PMID- 26811243 TI - Choosing wisely in case of hypertension, diabetes and hyperlipidemia in older patients. AB - BACKGROUND: The Choosing WiselyTM campaign was created by the American Board of Internal Medicine, it asks medical specialty societies to indicate five diagnostic and/or therapeutic interventions in their specialty to be avoided in specific cases. The aim of this campaign is to stimulate discussion between patients and their doctors about the usefulness of each procedure and also to avoid unnecessary, possibly wasteful measures. Hypertension, diabetes and hyperlipidemia are the most common conditions seen in primary care. The feasibility of applying the principles of Choosing Wisely in these cases was the target of this mini-review. METHODS: A PUBMED query based on entering the terms "choosing wisely", "elderly", "hypertension", "diabetes" and "hyperlipidemia" was performed. The search was limited to studies in human subjects using original articles and reviews in English and German that were published in the period of 1982-2015. In addition, a manual search from all relevant references and screened articles was performed. CONCLUSION: Using the up to date knowledge of precise indication for the pharmacological treatment of hypertension, diabetes and hyperlipidemia in older patients protects them from adverse effects and avoids interventions of low value. Additional tests of functionality like a frailty score or the comprehensive geriatric assessment can improve decision making for starting of medical interventions and for adjusting the intensity of treatment. Based on current literature they can help to withdraw or to abstain from unnecessary medical interventions. PMID- 26811244 TI - Associations of Inter- and Intraday Temperature Change With Mortality. AB - In this study we evaluated the association between temperature variation and mortality and compared it with the contribution due to mean daily temperature in 6 cities with different climates. Quasi-Poisson time series regression models were applied to estimate the associations (relative risk and 95% confidence interval) of mean daily temperature (99th and 1st percentiles, with temperature of minimum mortality as the reference category), interday temperature variation (difference between the mean temperatures of 2 neighboring days) and intraday temperature variation (diurnal temperature range (DTR)) (referred to as median variation) with mortality in 6 cities: London, United Kingdom; Madrid, Spain; Stockholm, Sweden; New York, New York; Miami, Florida; and Houston, Texas (date range, 1985-2010). All cities showed a substantial increase in mortality risk associated with mean daily temperature, with relative risks reaching 1.428 (95% confidence interval (CI): 1.329, 1.533) for heat in Madrid and 1.467 (95% CI: 1.385, 1.555) for cold in London. Inconsistent results for inter-/intraday change were obtained, except for some evidence of protective associations on hot and cold days (relative risk (RR) = 0.977 (95% CI: 0.955, 0.999) and RR = 0.981 (95% CI: 0.971, 0.991), respectively) in Madrid and on cold days in Stockholm (RR = 0.989, 95% CI: 0.980, 0.998). Our results indicate that the association between mortality and temperature variation is generally minimal compared with mean daily temperatures, although further research on intraday changes is needed. PMID- 26811245 TI - Weight management in obesity - past and present. AB - AIMS: To describe the treatment of obesity from ancient times to present day. METHODS: Articles reporting the development of anti-obesity therapies were identified through a search for 'anti-obesity' AND 'pharmacotherapy' AND 'development' within the title or abstract on PubMed and 'obesity' in ClinicalTrials.gov. Relevant articles and related literature were selected for inclusion. RESULTS: Stone-age miniature obese female statuettes indicate the existence and cultural significance of obesity as long as 30,000 years ago. Records from Ancient Egyptian and Biblical eras through Greco-Roman to Medieval times indicate that obesity was present throughout the major periods of history, although peoples of previous centuries would probably have experienced overweight and obesity as exceptional rather than normal. Health risks of obesity were noted by the Greek physician Hippocrates (460-377 BCE) when the earliest anti-obesity recommendations on diet, exercise, lifestyle and use of emetics and cathartics were born. These recommendations remained largely unchanged until the early 20th century, when spreading urbanisation, increasingly sedentary jobs and greater availability of processed foods produced a sharp rise in obesity. This led to the need for new, more effective, ways to lose weight, to address comorbidities associated with obesity, and to attain the current cultural ideal of slimness. Drug companies of the 1940s and 1950s produced a series of anti-obesity pharmacotherapies in short succession, based largely on amphetamines. Increased regulation of drug development in the 1960s and new efficacy requirements for weight-loss drugs led to rapid reduction in anti-obesity therapies available by the early 1990s. CONCLUSION: In the last two decades, several new and emerging therapies have been approved or are in development to provide safe, long-term pharmacological agents for the treatment of obesity. PMID- 26811246 TI - Permanent Loss of Preoperative Independence in Elderly Patients Undergoing Hepatectomy: Key Factor in the Informed Consent Process. AB - PURPOSE: Major (>3 segments of the liver) or minor hepatectomy has been demonstrated to provide the most definitive chance for long-term remission and disease-free survival in hepatic malignancies. However, concerns remain in regards to the ability of the elderly (>70 years old) and older (>80 years old) patients to "tolerate" this type of resection. Thus, the aim of this study was to determine the short- and long-term effects of hepatectomies in the elderly patient population. METHODS: An Institutional Review Board approved a prospectively maintained, single-institution HPB database with 663 consecutive hepatectomies from 2003 to 2013 was reviewed. Patients were separated into elderly (>70 years old) and older. Short-term effects were defined as a 30-day morbidity/mortality, and long-term effects were defined as a 90-day morbidity/mortality and the ability to regain preoperative functional independence. Comorbidities were compared using the Charleston Comorbidity Index (CCI). The log-rank and Wilcoxon tests were used to evaluate postoperative outcomes. RESULTS: A total of 663 patients were reviewed, 480 < 70y/o, 183 were 70 or older, 104 were 75 or older, and 41 were 80 or older. Patients over 70, 75, and 80 years of age showed a higher incidence of preoperative comorbidities than younger patients when compared using CCI (P < 0.05). Non-elderly patients had more liver lesions than elderly patients (median numbers only 3 vs. 1, P = 0.005). Patients over 70, 75, and 80 years old showed a higher 90-day mortality rate patients (11, 13, 17 %, respectively) to patients less than 70, 75 and 80 (3, 5, 5 %, respectively, P < 0.05) (Table). Patients over 70, 75, and 80 years old showed increased morbidity (53, 57, 66 %, respectively) than patients less than 70, 75, and 80 (39, 34, 41 %, respectively, P < 0.05). The severity of complication in elderly patients was similar to younger patients. Patients older than 70, 75, and 80 years showed an increased incidence of discharge to rehabilitation facilities (13, 15, 17 %, respectively) than patients less than 70, 75, and 80 (2, 3, 5 %, respectively, P = <0.001). Logistic regression demonstrated a significant risk of morbidity with an inability to return to preoperative function with a CCI > 5, major hepatectomy, and >75 years of age (HR 3.8, CI 2.1-5.6) CONCLUSIONS: This study demonstrates an increased rate of a 30- and 90-day postoperative mortality in >75-year old patients. Permanent loss of preoperative function (i.e., ability to live independently or alone) remains a significant risk and a subset of older patients. Communicating this loss of function as well as morbidity/mortality is key to the informed consent process for older patients as well as their families. PMID- 26811248 TI - [Preneoplastic lesions and precursors of urothelial cancer]. AB - As even a mere thickening of the urothelium can harbor genetic changes identical to that of low grade papillary urothelial tumors, it is not always possible to clearly recognize a precursor lesion of urothelial carcinoma by routine histological diagnostics. Complementary immunohistochemical and molecular diagnostic methods assist the recognition of these entities. These methods especially help to identify clinically important genetically unstable cells as the hallmark of carcinoma in situ (CIS). Little is known about the clinical significance of the morphological subtypes of CIS, which range from large cell to micropapillary variants. For a better understanding of special types of bladder cancer (e.g. adenocarcinoma and squamous cell carcinoma), it seems to be important to define the phenotype and the molecular pattern of non-urothelial lesions, such as intestinal metaplasia and squamous metaplasia, better and more precisely. PMID- 26811249 TI - A novel model for evaluating thrombolytic therapy in dogs with ST-elevation myocardial infarction. AB - BACKGROUND: There is still no standard large animal model for evaluating the effectiveness of potential thrombolytic therapies. Here, we aimed to develop a new beagle model with ST-elevation myocardial infarction (STEMI) by injecting autologous emboli with similar components of coronary thrombus. METHODS: 18 male beagles were included and divided into three groups: red embolus group (n = 6), white embolus group (n = 6) or white embolus + rt-PA group (n = 6). Autologous emboli were infused into the mid-distal region of the left anterior descending coronary artery. The composition of embolus was examined by scanning electron microscope (SEM). Coronary angiography was performed to verify the status of embolism. Myocardial infarct size was measured by 2, 3, 5- triphenyltetrazolium chloride (TTC) staining. RESULTS: Red thrombus was characteristic of loose reticular structure of erythrocytes under SEM, while the white embolus had compacted structure that mainly consisted of a dense mass of fibrin. Coronary angiography showed the recanalization rate was 2/6 in the red embolus group versus 0/6 in the white embolus group in three hours after occlusion. Arrhythmia, resolution of ST-segment elevation and lower T wave on the electrocardiogram appeared in the red embolus group but not in the white embolus group. Another six dogs with white thrombi were treated with rt-PA. Five out of six dogs exhibited coronary recanalization after two hours of therapy, compared to zero dogs without rt-PA treatment. The size of myocardial infarction in rt-PA group reduced significantly compared with white embolus group using TTC staining method. CONCLUSIONS: The white embolism model was more convenient experimentally and had a higher uniformity, stability and success rate. The major innovation of our study is that we applied fibrin-rich white thrombi to establish beagle model possessing features of clinically observed coronary thrombi in time window of intravenous thrombolysis of STEMI. This model can be used to evaluate new thrombolytic drugs for the treatment of STEMI. PMID- 26811250 TI - Evaluation of golimumab for the treatment of patients with active rheumatoid arthritis. AB - INTRODUCTION: Golimumab is a human anti-TNF monoclonal antibody that was derived from human antibody-transgenic mice. Golimumab demonstrated meaningful clinical benefit and tolerable safety in patients with active rheumatoid arthritis (RA) who were methotrexate (MTX)-naive, or who inadequately responded to MTX or who had previously been treated with a TNF inhibitor. AREAS COVERED: This review summarizes published data on the clinical efficacy and safety for golimumab (including its pharmacodynamic and pharmacokinetic characteristics) from multiple global phase III and Japanese phase II/III clinical trials. In the long term extension of three Phase III studies with subcutaneous golimumab, the reported retention rate is high. EXPERT OPINION: Golimumab binds TNF with high affinity and can be delivered subcutaneously every 4 weeks. Like other IgG1 antibodies, FcgammaR functions suggests that antibody dependent cellular cytotoxicity is observed but the contribution of cell lysis to efficacy is unclear. Although anti TNFalpha agents made it possible to achieve clinical remission in RA patients, there is still an unmet need to develop treatments that will enable them to discontinue all RA medication and maintain drug-free remission. PMID- 26811251 TI - Nigrostriatal denervation sine parkinsonism. PMID- 26811252 TI - The neural dynamics of reward value and risk coding in the human orbitofrontal cortex. AB - The orbitofrontal cortex is known to carry information regarding expected reward, risk and experienced outcome. Yet, due to inherent limitations in lesion and neuroimaging methods, the neural dynamics of these computations has remained elusive in humans. Here, taking advantage of the high temporal definition of intracranial recordings, we characterize the neurophysiological signatures of the intact orbitofrontal cortex in processing information relevant for risky decisions. Local field potentials were recorded from the intact orbitofrontal cortex of patients suffering from drug-refractory partial epilepsy with implanted depth electrodes as they performed a probabilistic reward learning task that required them to associate visual cues with distinct reward probabilities. We observed three successive signals: (i) around 400 ms after cue presentation, the amplitudes of the local field potentials increased with reward probability; (ii) a risk signal emerged during the late phase of reward anticipation and during the outcome phase; and (iii) an experienced value signal appeared at the time of reward delivery. Both the medial and lateral orbitofrontal cortex encoded risk and reward probability while the lateral orbitofrontal cortex played a dominant role in coding experienced value. The present study provides the first evidence from intracranial recordings that the human orbitofrontal cortex codes reward risk both during late reward anticipation and during the outcome phase at a time scale of milliseconds. Our findings offer insights into the rapid mechanisms underlying the ability to learn structural relationships from the environment. PMID- 26811253 TI - On the right side? A longitudinal study of left- versus right-lateralized semantic dementia. AB - The typical presentation of semantic dementia is associated with marked, left predominant anterior temporal lobe atrophy and with changes in language. About 30% of individuals, however, present with predominant right anterior temporal lobe atrophy, usually accompanied by behavioural changes and prosopagnosia. Here, we aimed to establish whether these initially distinct clinical presentations evolve into a similar syndrome at the neural and behavioural level. Thirty-one patients who presented with predominant anterior temporal lobe atrophy were included. Based on imaging, patients were categorized as either predominant left (n = 22) or right (n = 9) semantic dementia. Thirty-three Alzheimer's disease patients and 25 healthy controls were included for comparison. Participants completed the Addenbrooke's Cognitive Examination, a Face and Emotion Processing Battery and the Cambridge Behavioural Inventory, and underwent magnetic resonance imaging annually. Longitudinal neuroimaging analyses showed greater right temporal pole atrophy in left semantic dementia than Alzheimer's disease, whereas right semantic dementia showed greater orbitofrontal and left temporal lobe atrophy than Alzheimer's disease. Importantly, direct comparisons between semantic dementia groups revealed that over time, left semantic dementia showed progressive thinning in the right temporal pole, whereas right semantic dementia showed thinning in the orbitofrontal cortex and anterior cingulate. Behaviourally, longitudinal analyses revealed that general cognition declined in all patients. In contrast, patients with left and right semantic dementia showed greater emotion recognition decline than Alzheimer's disease. In addition, left semantic dementia showed greater motivation loss than Alzheimer's disease. Correlational analyses revealed that emotion recognition was associated with right temporal pole, right medial orbitofrontal and right fusiform integrity, while changes in motivation were associated with right temporal pole cortical thinning. While left and right semantic dementia show distinct profiles at presentation, both phenotypes develop deficits in emotion recognition and behaviour. These findings highlight the pervasive socio-emotional deficits in frontotemporal dementia, even in patients with an initial language presentation. These changes reflect right anterior temporal and orbitofrontal cortex degeneration, underscoring the role of these regions in social cognition and behaviour. PMID- 26811254 TI - Mentalizing the body: spatial and social cognition in anosognosia for hemiplegia. AB - Following right-hemisphere damage, a specific disorder of motor awareness can occur called anosognosia for hemiplegia, i.e. the denial of motor deficits contralateral to a brain lesion. The study of anosognosia can offer unique insights into the neurocognitive basis of awareness. Typically, however, awareness is assessed as a first person judgement and the ability of patients to think about their bodies in more 'objective' (third person) terms is not directly assessed. This may be important as right-hemisphere spatial abilities may underlie our ability to take third person perspectives. This possibility was assessed for the first time in the present study. We investigated third person perspective taking using both visuospatial and verbal tasks in right-hemisphere stroke patients with anosognosia (n = 15) and without anosognosia (n = 15), as well as neurologically healthy control subjects (n = 15). The anosognosic group performed worse than both control groups when having to perform the tasks from a third versus a first person perspective. Individual analysis further revealed a classical dissociation between most anosognosic patients and control subjects in mental (but not visuospatial) third person perspective taking abilities. Finally, the severity of unawareness in anosognosia patients was correlated to greater impairments in such third person, mental perspective taking abilities (but not visuospatial perspective taking). In voxel-based lesion mapping we also identified the lesion sites linked with such deficits, including some brain areas previously associated with inhibition, perspective taking and mentalizing, such as the inferior and middle frontal gyri, as well as the supramarginal and superior temporal gyri. These results suggest that neurocognitive deficits in mental perspective taking may contribute to anosognosia and provide novel insights regarding the relation between self-awareness and social cognition. PMID- 26811255 TI - Disruption of brain anatomical networks in schizophrenia: A longitudinal, diffusion tensor imaging based study. AB - Despite convergent neuroimaging evidence indicating a wide range of brain abnormalities in schizophrenia, our understanding of alterations in the topological architecture of brain anatomical networks and how they are modulated over time, is still rudimentary. Here, we employed graph theoretical analysis of longitudinal diffusion tensor imaging data (DTI) over a 5-year period to investigate brain network topology in schizophrenia and its relationship with clinical manifestations of the illness. Using deterministic tractography, weighted brain anatomical networks were constructed from 31 patients experiencing schizophrenia and 28 age- and gender-matched healthy control subjects. Although the overall small-world characteristics were observed at both baseline and follow up, a scan-point independent significant deficit of global integration was found in patients compared to controls, suggesting dysfunctional integration of the brain and supporting the notion of schizophrenia as a disconnection syndrome. Specifically, several brain regions (e.g., the inferior frontal gyrus and the bilateral insula) that are crucial for cognitive and emotional integration were aberrant. Furthermore, a significant group-by-longitudinal scan interaction was revealed in the characteristic path length and global efficiency, attributing to a progressive aberration of global integration in patients compared to healthy controls. Moreover, the progressive disruptions of the brain anatomical network topology were associated with the clinical symptoms of the patients. Together, our findings provide insights into the substrates of anatomical dysconnectivity patterns for schizophrenia and highlight the potential for connectome-based metrics as neural markers of illness progression and clinical change with treatment. PMID- 26811257 TI - Adapting and remodelling the US Institute for Safe Medication Practices' Medication Safety Self-Assessment tool for hospitals to be used to support national medication safety initiatives in Finland. AB - BACKGROUND: The US Institute for Safe Medication Practices' (ISMP) Medication Safety Self-Assessment (MSSA) tool for hospitals is a comprehensive tool for assessing safe medication practices in hospitals. AIMS: To adapt and remodel the ISMP MSSA tool for hospitals so that it can be used in individual wards in order to support long-term medication safety initiatives in Finland. METHODS: The MSSA tool was first adapted for Finnish hospital settings by a four-round (applicability, desirability and feasibility were evaluated) Delphi consensus method (14 panellists), and then remodelled by organizing the items into a new order which is consistent with the order of the ward-based pharmacotherapy plan recommended by the Ministry of Social Affairs and Health. The adapted and remodelled tool was pilot tested in eight central hospital wards. KEY FINDINGS: The original MSSA tool (231 items under ten key elements) was modified preliminarily before the Delphi rounds and 117 items were discarded, leaving 114 items for Delphi evaluation. The panel suggested 36 new items of which 23 were accepted. A total of 114 items (including 91 original and 23 new items) were accepted and remodelled under six new components that were pilot tested. The pilot test found the tool time-consuming but useful. CONCLUSION: It was possible to adapt the ISMP's MSSA tool for another hospital setting. The modified tool can be used for a hospital pharmacy coordinated audit which supports long-term medication safety initiatives, particularly the establishment of ward-based pharmacotherapy plans as guided by the Ministry of Social Affairs and Health. PMID- 26811256 TI - Impaired hippocampal-dependent memory and reduced parvalbumin-positive interneurons in a ketamine mouse model of schizophrenia. AB - The hippocampus of patients with schizophrenia displays aberrant excess neuronal activity which affects cognitive function. Animal models of the illness have recapitulated the overactivity in the hippocampus, with a corresponding regionally localized reduction of inhibitory interneurons, consistent with that observed in patients. To better understand whether cognitive function is similarly affected in these models of hippocampal overactivity, we tested a ketamine mouse model of schizophrenia for cognitive performance in hippocampal- and medial prefrontal cortex (mPFC)-dependent tasks. We found that adult mice exposed to ketamine during adolescence were impaired on a trace fear conditioning protocol that relies on the integrity of the hippocampus. Conversely, the performance of the mice was normal on a delayed response task that is sensitive to mPFC damage. We confirmed that ketamine-exposed mice had reduced parvalbumin positive interneurons in the hippocampus, specifically in the CA1, but not in the mPFC in keeping with the behavioral findings. These results strengthened the utility of the ketamine model for preclinical investigations of hippocampal overactivity in schizophrenia. PMID- 26811258 TI - Overweight and obesity predict better overall survival rates in cancer patients with distant metastases. AB - Recent studies conducted in patients with chronic diseases have reported an inverse association between body mass index (BMI) and mortality. However, the question as to whether BMI may predict prognosis in patients with metastatic cancer remains open. We therefore designed the current retrospective study to investigate the potential association between BMI and overall survival (OS) in patients with distant metastases (DM) and a favorable performance status. Between 2000 and 2012, a total of 4010 cancer patients with DM who required radiotherapy (RT) and had their BMI measured at the initiation of RT were identified. The relation between BMI and OS was examined by univariate and multivariable analysis. The median OS time was 3.23 months (range: 0.1-122.17) for underweight patients, 6.08 months (range: 0.03-149.46) for normal-weight patients, 7.99 months (range: 0.07-158.01) for overweight patients, and 12.49 months (range, 0.2 164.1) for obese patients (log-rank: P < 0.001). Compared with normal-weight patients, both obese (HR = 0.676; 95% P < 0.001) and overweight individuals (HR = 0.84; P < 0.001) had a reduced risk of all-cause mortality in multivariable analysis. Conversely, underweight patients had a significantly higher risk of death from all causes (HR = 1.41; P < 0.001). Overweight and obesity are independent predictors of better OS in metastatic patients with a good performance status. Increased BMI may play a role to identify metastatic patients with superior survival outcome and exhibit a potential to encourage aggressive management in those patients even with metastases. PMID- 26811259 TI - The effect of continuous ELF-MFs on the level of 5-HIAA in the raphe nucleus of the rat. AB - The aim of this study was to investigate the effect of continuous extremely low frequency magnetic fields (ELF-MFs) with a frequency of 10 Hz and an intensity of 690-720 MUT on the level of 5-hydroxyindolacetic acid (5-HIAA) in adult male Wistar rats. A total of 24 adult Wistar male rats were used, and after exposure with an ELF-MF for 15 successive days, all rats in each test were anesthetized with chloral hydrate. Then, they were placed in a stereotaxic frame for surgery and a microdialysis process. Dialysate samples were analyzed to measure the amount of 5-HIAA by high performance liquid chromatography (HPLC) using electrochemical detection. Results showed that ELF-MF exposure for 15 days, 1 h daily, was not effective in altering the level of 5-HIAA. However, ELF-MF exposure for 15 days, 3 h daily, decreased the level of the 5-HIAA in the raphe nucleus. It can be concluded that ELF-MFs affect the serotonergic system and may be used to treat nervous system diseases. This study is an initial step towards helping cure depression using ELF-MFs. PMID- 26811260 TI - Piwil1 mediates meiosis during spermatogenesis in chicken. AB - Piwil1 mediates spermatogenesis and ensures stable cell division rates in germline cells in mammals. However, the involvement of Piwil1 in poultry spermatogenesis and meiosis is poorly understood. In the present study, we used TaqMan RT-qPCR to characterize Piwil1 mRNA expression in different types of spermatogenic cells, including primordial germ cells (PGCs), spermatogonial stem cells (SSCs), spermatogonia cells (Sa), tetraploid cells (Tp), round sperm cells (Rs), mature sperm, and in PGCs treated with retinoic acid. Our results revealed that Piwil1 is differentially expressed during spermatogenesis in chicken. Compared to PGCs, SSCs, Tp, and Sa, Rs cells presented the highest Piwil1 mRNA expression levels. Retinoic acid significantly upregulated Piwil1 and Stra8 mRNA expression as well as Piwil1 levels in chicken PGCs. In addition, retinoic acid induced PGCs to progress through all the meiotic stages, eventually leading to haploid cell formation, which was determined using flow cytometry and western blot analysis. Taken together, our results showed that during spermatogenesis, Piwil1 was first expressed at low levels in germ stem cells, PGCs, and SSCs. Its expression levels increased during later meiosis stages. Finally, no expression was detected in mature sperm after meiosis. Treatment of PGCs with retinoic acid further demonstrated that Piwil1 plays a key role in meiosis during chicken spermatogenesis. PMID- 26811261 TI - Transapical implantation of a self-expandable aortic valve prosthesis utilizing a novel designed positioning element. AB - OBJECTIVES: To evaluate a new transapical system which utilizes a novel designed positioning element and a two-step positioning mechanism for easy and accurate implantation of transcatheter valves. BACKGROUND: Transcatheter aortic valve implantation is an important treatment option for non-surgical patients with severe aortic stenosis. However, accurate placement of the transcatheter valve remains challenging. METHODS: Self-expandable aortic valve prosthesis with a flexibly connected, annulus-like positioning element was implanted through a transapical approach in 12 pigs. The positioning element was separated and can be released independent of the valve prosthesis. During valve implantation, firstly, the positioning element was unsheathed and fixed into the aortic sinus. Then, the prosthetic valve was guided to an anatomically oriented position and deployed. Six animals were followed up to 180 days. RESULTS: With the help of the positioning element, all 12 valves were successfully deployed at the anticipated site. The valve release procedure took an average of 7.3 +/- 2.5 min. The mean transvalvular pressure gradient was 2.8 +/- 1.1 mm Hg at valve deployment. Of the six chronic animals, the mean transvalvular pressure gradient was 3.0 +/- 1.0 mm Hg on day 7, and 2.9 +/- 1.6 mm Hg on day 180 (P = 0.91). No migration, embolization, or coronary obstruction was observed during surgery and at necropsy. Pathological examination showed anatomically correct positioning of the prosthetic valve without signs of thrombosis or calcification. CONCLUSIONS: In this study, we confirmed the feasibility of the J-Valve transapical system for transapical implantation through a two-step process. Satisfactory hemodynamic and pathological performance during a follow-up of 180 days was demonstrated. (c) 2016 Wiley Periodicals, Inc. PMID- 26811262 TI - A descriptive regional study of drug and alcohol use in pregnant women using results from urine drug testing by liquid chromatography-tandem mass spectrometry. AB - BACKGROUND: Patterns of drug use during pregnancy may be changing. Identifying changes in pregnant women's drug use may help to target prevention and treatment. OBJECTIVE: To determine the regional prevalence of drug and alcohol use among pregnant women in Southern California. METHODS: This was a prospective, descriptive study conducted at a university health system's urban and suburban ambulatory obstetric offices. Included were pregnant women of all ages and trimesters. Excluded were non-pregnant women and women who had previously presented for an obstetric appointment during the data collection time period. Women provided a urine sample as part of routine care. Liquid chromatography tandem mass spectrometry analysis of urine was performed for detection of a pre selected sample of drugs and for alcohol. Descriptive statistics were performed. RESULTS: A total of 295 urine samples were included. All trimesters were represented. A total of 14.2% of urine samples were positive for at least one of the tested drugs or alcohol. Alcohol was detected in 6% of the urine samples and was the most frequently identified substance. Prescription opioid analgesics (3.7% detection rate) and marijuana (4% detection rate) were the other most frequently detected substances. CONCLUSIONS: Compared with older reports, our detection rates of prescription opioid analgesics were increased while rates of urinary alcohol detection were relatively unchanged, and detection rates of marijuana were decreased. Provider awareness of these substance detection rates may facilitate the identification of patients using these substances during pregnancy and ultimately help promote potential prevention and treatment. PMID- 26811263 TI - Enhanced Approaches for Identifying Amadori Products: Application to Peanut Allergens. AB - The dry roasting of peanuts is suggested to influence allergic sensitization as a result of the formation of advanced glycation end products (AGEs) on peanut proteins. Identifying AGEs is technically challenging. The AGEs of a peanut allergen were probed with nano-scale liquid chromatography-electrospray ionization-mass spectrometry (nanoLC-ESI-MS) and tandem mass spectrometry (MS/MS) analyses. Amadori product ions matched to expected peptides and yielded fragments that included a loss of three waters and HCHO. As a result of the paucity of b and y ions in the MS/MS spectrum, standard search algorithms do not perform well. Reactions with isotopically labeled sugars confirmed that the peptides contained Amadori products. An algorithm was developed on the basis of information content (Shannon entropy) and the loss of water and HCHO. Results with test data show that the algorithm finds the correct spectra with high precision, reducing the time needed to manually inspect data. Computational and technical improvements allowed for better identification of the chemical differences between modified and unmodified proteins. PMID- 26811264 TI - Diagnosing Glucose Transporter 1 Deficiency at Initial Presentation Facilitates Early Treatment. AB - OBJECTIVE: To profile the initial clinical events of glucose transporter 1 deficiency syndrome (Glut1 DS) in order to facilitate the earliest possible diagnosis. STUDY DESIGN: We retrospectively reviewed 133 patients with Glut1 DS from a single institution. Family interviews and medical record reviews identified the first clinical event(s) reported by the caregivers. RESULTS: Average age of the first event was 8.15 +/- 11.9 months (range: 0.01-81). Ninety one patients experienced the first symptom before age 6 months (68%). Thirty three additional patients (25%) presented before age 2 years. Only 9 patients (7%), reported the first event after age 2 years. Seizures were the most common first event (n = 81, 61%), followed by eye movement abnormalities (n = 51, 38%) and changes in muscle strength and tone (n = 30, 22%). Eye movement abnormalities, lower cerebrospinal fluid glucose values, and lower Columbia Neurological Scores correlated with earlier onset of the first event (r: -0.17, 0.22, and 0.25 respectively, P < .05). There was no correlation with age of first event and red blood cell glucose uptake or mutation type. CONCLUSIONS: Glut1 DS is a treatable cause of infantile onset encephalopathy. Health care providers should recognize the wide spectrum of paroxysmal events that herald the clinical onset of Glut1 DS in early infancy to facilitate prompt diagnosis, immediate treatment, and improved long-term outcome. PMID- 26811266 TI - Regional calcified plaque score evaluated by multidetector computed tomography for predicting the addition of rotational atherectomy during percutaneous coronary intervention. AB - BACKGROUND: Rotational atherectomy (rotablation) has been proposed as a potentially superior strategy for percutaneous coronary intervention (PCI) in complex and severely calcified lesions. OBJECTIVES: We hypothesized that a per lesion coronary artery calcium score determined by multidetector computed tomography (MDCT) would be useful for predicting the requriement for rotablation during PCI. METHODS: MDCT was performed in patients with stable angina pectoris who were scheduled for first PCI. In 116 consecutive subjects (168 target lesions) with successful PCI, MDCT and quantitative coronary angiography (QCA) data were retrospectively evaluated regarding their ability to predict rotablation. RESULTS: PCI without rotablation was performed in 105 patients (154 lesions), and rotablation was added in 11 patients (14 lesions). Patients with rotablation had significantly higher SYNTAX scores (p = 0.007) and total calcium scores (p < 0.001) than those without rotablation. Per-lesion, a lesion length >=20 mm and diameter stenosis >=74% on QCA as well as a per-lesion calcium score >=453 and calcification arc >=270 in MDCT predicted rotablation. After adjustment for potential confounding variables, a high per-lesion calcium score was an independent predictor of rotablation (odds ratio 31.3, 95% confidence interval 2.8-345, p = 0.005, sensitivity 93% and specificity 88%). CONCLUSION: The extent of target lesion calcification in MDCT, a simple marker of calcified plaque, is useful for predicting the need for rotablation during PCI. PMID- 26811268 TI - Sulfonamide-directed gold-catalyzed [2+2+2]-cycloadditions of nitriles with two discrete ynamides to construct 2,4-diaminopyridine cores. AB - Gold-catalyzed [2+2+2]-cycloadditions of two discrete ynamides and one nitrile afford 2,4-diaminopyridine derivatives that are not readily prepared from typical low-valent-metal catalysts. Our mechanistic analysis reveals that the reaction chemoselectivity is controlled by the types of sulfonamides of ynamides. PMID- 26811267 TI - [Consensus for pharmacologic treatment of atherogenic dyslipidemia with statin fenofibrate combined therapy]. AB - LDLc levels are associated with increase of cardiovascular risk, and statins are currently used for their control. Nevertheless, a despite of LDLc levels at goal, a residual risk is persistent, commonly associated with persistent lipids modifications (high triglycerides and low HDLc). So, it is necessary to evaluate triglycerides and HDL to assessment cardiovascular risk. Clinical data are consistent with efficacy and safety of combination therapy with statin and other lipid lowering drugs, for instance fenofibrate. Patients with hipertriglyceridemia and low HDLc are the group with most potential improve. In that patients with atherogenic dyslipidemia, the target for therapeutic objectives related with non-HDL-cholesterol is a priority, because non-HDL cholesterol is considered as a more accuracy measure to assessment cardiovascular risk. PMID- 26811269 TI - Interaction between thyrocytes and adipose tissue in vitro. AB - Adipose tissue (AT)-thyrocyte interaction is largely unknown. Here we described the interaction in a co-culture system, in which thyrocytes were cultured on AT fragment (ATF)-embedded collagen gel, using electron microscopy, immunocytochemistry, real-time reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). ATFs promoted the hypertrophy, polarization and lipid accumulation of thyrocytes. ATFs did not affect the growth of thyroyctes, and inhibited their apoptosis. ATFs increased the protein expression of thyroglobulin (Tg) and paired box gene 8 (PAX8) in thyrocytes. In turn, thyrocytes decreased the concentration of leptin and adiponectin, and increased the expression of these mRNAs in ATFs. Thyrotropin (TSH) enhanced the ATF-induced nuclear hypertrophy and Tg protein expression in thyrocytes, while TSH enhanced the thyrocyte-induced expression of leptin and adiponectin mRNAs in ATFs. Finally, leptin promoted the hypertrophy and Tg protein expression in thyrocytes. TSH enhanced these leptin-induced effects. The data indicate an active interaction between thyrocytes and AT, suggesting that (i) ATFs may serve to regulate the morphology, survival and differentiation of thyrocytes probably through lipid accumulation partly in a TSH-synergistic way; (ii) thyrocytes may affect adipokine production from ATFs in a TSH-independent manner; and (3) leptin may be related to the hypertrophy and differentiation of thyrocytes in a TSH-synergistic way. PMID- 26811270 TI - Intraoperative Transesophageal Echocardiography for the Evaluation and Management of Diastolic Dysfunction in Patients Undergoing Cardiac Surgery: A Survey of Current Practice. AB - OBJECTIVES: To characterize existing practice patterns for intraoperative evaluation and grading of diastolic dysfunction in patients undergoing cardiac surgery. DESIGN: A 14-question, multiple-choice survey of current practice for patients with diastolic dysfunction and the use of intraoperative transesophageal echocardiography (TEE) to evaluate, grade, and monitor changes in diastolic function. SETTING: Online survey. PARTICIPANTS: Members of the Society of Cardiovascular Anesthesiologists. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 515 respondents, there was a near-even spread between those based in an academic setting (53%) and those based in private practice (43%). Most respondents (81%) had completed training with certification in TEE. Most respondents (86%) currently modified their intraoperative management, at least some of the time, if they believed a patient was experiencing diastolic dysfunction, with 72% varying the nature of any modification according to the identified grade of diastolic dysfunction. Although 62% of respondents usually evaluated diastolic dysfunction in the pre-bypass period, only 59% of those evaluating diastolic dysfunction typically graded the dysfunction, with a variety of algorithms used for this purpose. The majority of respondents (62%) typically did not re-evaluate diastolic function using TEE in the post-bypass period. In 2 sample patients with Doppler data provided, there was marked variation in grading of diastolic dysfunction by respondents; this variation remained marked even within subgroups of respondents who typically used the same grading algorithm. CONCLUSIONS: Marked variation currently exists in how intraoperative TEE is used to evaluate, grade, and monitor diastolic function during cardiac surgery. This suggests clinically important knowledge gaps that should be addressed. PMID- 26811271 TI - Ruptured Abdominal Aortic Aneurysm: Prediction of Mortality From Clinical Presentation and Glasgow Aneurysm Score. AB - OBJECTIVE: To examine association of presenting clinical acuity and Glasgow Aneurysm Score (GAS) with perioperative and 1-year mortality. DESIGN: Retrospective chart review. SETTING: Major tertiary care facility. PARTICIPANTS: Patients with ruptured abdominal aortic aneurysm (rAAA) from 2003 through 2013. INTERVENTIONS: Emergency repair of rAAA. MEASUREMENTS AND MAIN RESULTS: The authors reviewed outcomes after stable versus unstable presentation and by GAS. Unstable presentation included hypotension, cardiac arrest, loss of consciousness, and preoperative tracheal intubation. In total, 125 patients (40 stable) underwent repair. Perioperative mortality rates were 41% and 12% in unstable and stable patients, respectively (p<0.001). Unstable status had 88% sensitivity and 41% specificity for predicting perioperative mortality. Using logistic regression, higher GAS was associated with perioperative mortality (p<0.001). Using receiver operating characteristic analysis, the area under the curve was 0.72 (95% CI, 0.62-0.82) and cutoff GAS>=96 had 63% and 72% sensitivity and specificity, respectively. Perioperative mortality for GAS>=96 was 51% (25/49), whereas it was 20% (15/76) for GAS<=95. The estimated 1-year survival (95% CI) was 75% (62%-91%) for stable patients and 48% (38%-60%) for unstable patients. Estimated 1-year survival (95% CI) was 23% (13%-40%) for GAS>=96 and 77% (67%-87%) for GAS<=95. CONCLUSIONS: Clinical presentation and GAS identified patients with rAAA who were likely to have a poor surgical outcome. GAS>=96 was associated with poor long-term survival, but>20% of these patients survived 1 year. Thus, neither clinical presentation nor GAS provided reliable guidance for decisions regarding futility of surgery. PMID- 26811272 TI - Cardiovascular Health in Brazil: Trends and Perspectives. AB - Brazil is a large country, with an evolving economy, but marked social inequalities. The population is formed by an admixture of native Brazilians, Europeans, and Africans; is predominantly urban; and faces rapid aging. Time trends related to health behaviors show a substantial reduction in smoking rates, but a rising prevalence of overweight and obesity, unhealthy eating habits, and insufficient physical activity. The high prevalence of hypertension and the increasing prevalence of diabetes mellitus are also causes for concern. Cardiovascular disease (CVD) has been the leading cause of mortality since the 1960s and has accounted for a substantial percentage of all hospitalizations. In 2011, CVD was responsible for 31% of all deaths, with ischemic heart disease (31%) and cerebrovascular diseases (30%) being the leading CVD causes. Despite an increase in the overall number of CVD deaths, the age-adjusted mortality rates for CVD declined 24% between 2000 and 2011. Health care delivered by Brazil's universal public health system, which focuses on primary prevention, has contributed to this achievement. However, the decline in age-adjusted mortality differs according to race, sex, and socioeconomic status with black individuals and lower-income populations sustaining the greatest impact of CVD, especially at younger ages. With one of the world's largest public health systems in terms of population coverage, Brazil has the means to implement actions to confront the high burden of CVD, focusing on health promotion and comprehensive care. Insufficient funding, low education levels, and social inequalities remain as the main barriers to be overcome. PMID- 26811273 TI - Are Zebras Simply Striped Horses? PMID- 26811274 TI - ECG Response: January 26, 2016. PMID- 26811275 TI - Multiple Peripheral Pulmonary Artery Aneurysms in Association With a Right Atrial Myxoma. PMID- 26811276 TI - Executive Summary: Heart Disease and Stroke Statistics--2016 Update: A Report From the American Heart Association. PMID- 26811277 TI - Case of Ebstein Anomaly Complicated by Left Ventricular Outflow Tract Obstruction Secondary to Deformed Basal Septum Attributable to Atrialized Right Ventricle. PMID- 26811278 TI - Letter by Patane Regarding Article, "Early Detection of Anthracycline Cardiotoxicity and Improvement With Heart Failure Therapy". PMID- 26811279 TI - Letter by Gallucci and Simeon Regarding Article, "Early Detection of Anthracycline Cardiotoxicity and Improvement With Heart Failure Therapy". PMID- 26811280 TI - Response to Letters Regarding Article, "Early Detection of Anthracycline Cardiotoxicity and Improvement With Heart Failure Therapy". PMID- 26811281 TI - Letter by Patane Regarding Article, "Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia: The Role of Left Cardiac Sympathetic Denervation". PMID- 26811282 TI - Letter by Gow Regarding Article, "Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia: The Role of Left Cardiac Sympathetic Denervation". PMID- 26811284 TI - Correction. PMID- 26811283 TI - Response to Letters Regarding Article, "Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia: The Role of Left Cardiac Sympathetic Denervation". PMID- 26811285 TI - Evolution, Regulation, and Function of N-terminal Variable Region of Troponin T: Modulation of Muscle Contractility and Beyond. AB - Troponin T (TnT) is the tropomyosin-binding and thin filament-anchoring subunit of the troponin complex in skeletal and cardiac muscles. At the center of the sarcomeric thin filament regulatory system of striated muscles, TnT plays an essential role in transducing Ca(2+) signals in the regulation of contraction. Having emerged predating the history of vertebrates, TnT has gone through more than 500 million years of evolution that resulted in three muscle-type-specific isoforms and numerous alternative RNA splicing variants. The N-terminal region of TnT is a hypervariable structure responsible for the differences among the TnT isoforms and splice forms. This focused review summarizes our current knowledge of the molecular evolution of the N-terminal variable region and its role in the structure and function of TnT. In addition to the physiologic and pathophysiologic significances in modifying the contractility of skeletal and cardiac muscles during development and in adaptation to stress and disease conditions, the hyperplasticity of the N-terminal region of TnT demonstrates an informative example for the evolution of protein three-dimensional structure and provides insights into the molecular evolution and functional potential of proteins. PMID- 26811287 TI - Microtubule Dynamics in Neuronal Development, Plasticity, and Neurodegeneration. AB - Neurons are the basic information-processing units of the nervous system. In fulfilling their task, they establish a structural polarity with an axon that can be over a meter long and dendrites with a complex arbor, which can harbor ten thousands of spines. Microtubules and their associated proteins play important roles during the development of neuronal morphology, the plasticity of neurons, and neurodegenerative processes. They are dynamic structures, which can quickly adapt to changes in the environment and establish a structural scaffold with high local variations in composition and stability. This review presents a comprehensive overview about the role of microtubules and their dynamic behavior during the formation and maturation of processes and spines in the healthy brain, during aging and under neurodegenerative conditions. The review ends with a discussion of microtubule-targeted therapies as a perspective for the supportive treatment of neurodegenerative disorders. PMID- 26811288 TI - Fish Chromatophores--From Molecular Motors to Animal Behavior. AB - Chromatophores are pigment-bearing cells of lower vertebrates, including fish that cater for the ability of individual animals to shift body coloration and pattern. Color change provides dynamic camouflage and various kinds of communication. It is also a spectacular example of phenotypic plasticity, and of significant importance for adaptation and survival in novel environments. Through different cellular mechanisms, color change can occur within minutes or more slowly over weeks. Chromatophores have different pigment types and are located not only in the skin, but also in the eyes and internally. While morphological color change, including seasonal color change, has received a lot of interest from evolutionary biologists and behavioral ecologists, the more rapid physiological color change has been largely a research subject for cell physiologists. In this cross-disciplinary review, we have highlighted emerging trends in pigment cell research and identified unsolved problems for future research. PMID- 26811289 TI - Molecular Breeding of Sorghum bicolor, A Novel Energy Crop. AB - Currently, molecular breeding is regarded as an important tool for the improvement of many crop species. However, in sorghum, recently heralded as an important bioenergy crop, progress in this field has been relatively slow and limited. In this review, we present existing efforts targeted at genetic characterization of sorghum mutants. We also comprehensively review the different attempts made toward the isolation of genes involved in agronomically important traits, including the dissection of some sorghum quantitative trait loci (QTLs). We also explore the current status of the use of transgenic techniques in sorghum, which should be crucial for advancing sorghum molecular breeding. Through this report, we provide a useful benchmark to help assess how much more sorghum genomics and molecular breeding could be improved. PMID- 26811290 TI - Cell-Nonautonomous Mechanisms Underlying Cellular and Organismal Aging. AB - Cell-autonomous mechanisms underlying cellular and organismal aging in evolutionarily distant eukaryotes have been established; these mechanisms regulate longevity-defining processes within a single eukaryotic cell. Recent findings have provided valuable insight into cell-nonautonomous mechanisms modulating cellular and organismal aging in eukaryotes across phyla; these mechanisms involve a transmission of various longevity factors between different cells, tissues, and organisms. Herein, we review such cell-nonautonomous mechanisms of aging in eukaryotes. We discuss the following: (1) how low molecular weight transmissible longevity factors modulate aging and define longevity of cells in yeast populations cultured in liquid media or on solid surfaces, (2) how communications between proteostasis stress networks operating in neurons and nonneuronal somatic tissues define longevity of the nematode Caenorhabditis elegans by modulating the rates of aging in different tissues, and (3) how different bacterial species colonizing the gut lumen of C. elegans define nematode longevity by modulating the rate of organismal aging. PMID- 26811291 TI - OSBP-Related Protein Family: Mediators of Lipid Transport and Signaling at Membrane Contact Sites. AB - Oxysterol-binding protein (OSBP) and its related protein homologs, ORPs, constitute a conserved family of lipid-binding/transfer proteins (LTPs) expressed ubiquitously in eukaryotes. The ligand-binding domain of ORPs accommodates cholesterol and oxysterols, but also glycerophospholipids, particularly phosphatidylinositol-4-phosphate (PI4P). ORPs have been implicated as intracellular lipid sensors or transporters. Most ORPs carry targeting determinants for the endoplasmic reticulum (ER) and non-ER organelle membrane. ORPs are located and function at membrane contact sites (MCSs), at which ER is closely apposed with other organelle limiting membranes. Such sites have roles in lipid transport and metabolism, control of Ca(2+) fluxes, and signaling events. ORPs are postulated either to transport lipids over MCSs to maintain the distinct lipid compositions of organelle membranes, or to control the activity of enzymes/protein complexes with functions in signaling and lipid metabolism. ORPs may transfer PI4P and another lipid class bidirectionally. Transport of PI4P followed by its hydrolysis would in this model provide the energy for transfer of the other lipid against its concentration gradient. Control of organelle lipid compositions by OSBP/ORPs is important for the life cycles of several pathogenic viruses. Targeting ORPs with small-molecular antagonists is proposed as a new strategy to combat viral infections. Several ORPs are reported to modulate vesicle transport along the secretory or endocytic pathways. Moreover, antagonists of certain ORPs inhibit cancer cell proliferation. Thus, ORPs are LTPs, which mediate interorganelle lipid transport and coordinate lipid signals with a variety of cellular regimes. PMID- 26811286 TI - Phosphatidylethanolamine Metabolism in Health and Disease. AB - Phosphatidylethanolamine (PE) is the second most abundant glycerophospholipid in eukaryotic cells. The existence of four only partially redundant biochemical pathways that produce PE, highlights the importance of this essential phospholipid. The CDP-ethanolamine and phosphatidylserine decarboxylase pathways occur in different subcellular compartments and are the main sources of PE in cells. Mammalian development fails upon ablation of either pathway. Once made, PE has diverse cellular functions that include serving as a precursor for phosphatidylcholine and a substrate for important posttranslational modifications, influencing membrane topology, and promoting cell and organelle membrane fusion, oxidative phosphorylation, mitochondrial biogenesis, and autophagy. The importance of PE metabolism in mammalian health has recently emerged following its association with Alzheimer's disease, Parkinson's disease, nonalcoholic liver disease, and the virulence of certain pathogenic organisms. PMID- 26811293 TI - Assessment of reproductive performance of Begait cattle in in-situ and ex-situ sites and in different production systems in northern Ethiopia. AB - Retrospective studies were conducted in Kafta-Humera and Wukro areas of Tigray region of Ethiopia. A retrospective study was carried out on 12 herds consisting 2144 Begait cattle from pastoral and agro-pastoral areas to assess herd composition and calf-crop. To evaluate the reproductive performance, 210 cows were selected randomly from pastoral, agro-pastoral, confinement and crop livestock production systems. All necessary data of reproductive parameters were collected through questionnaire surveys, group discussions and follow-up observations. SPSS software was applied to analyze the data. The result of the present study showed that the average calf-crop of 53% and 42.1% and annual calf mortality rate of 20.8% and 9.4%, were observed for pastoral and agro-pastoral production systems, respectively. The mean age at first service (AFS), age at first calving (AFC) and calving interval (CI) in months were 34.9, 43.9 and 12.9 in pastoral, 35.9, 45.0 and 14.0 in agro-pastoral, 34.4, 44.9 and 15.0 in confinement and 40.5, 49.5 and 19.6 in crop-livestock production systems, respectively. AFC and CI were significantly (P<0.05) affected by site and production system. Significantly longer AFS, AFC and CI were noticed in crop livestock system than in the other 3 production systems. However, CI was not affected by age and parity. PMID- 26811292 TI - The fast-off hypothesis revisited: A functional kinetic study of antipsychotic antagonism of the dopamine D2 receptor. AB - Newer, "atypical" antipsychotics carry a lower risk of motor side-effects than older, "typical" compounds. It has been proposed that a ~100-fold faster dissociation from the dopamine D2 receptor (D2R) distinguishes atypical from typical antipsychotics. Furthermore, differing antipsychotic D2R affinities have been suggested to reflect differences in dissociation rate constants (koff), while association rate constants (kon) were assumed to be similar. However, it was recently demonstrated that lipophilic accumulation of ligand in the cell interior and/or membrane can cause underestimation of koff, and as high-affinity D2R antagonists are frequently lipophilic, this may have been a confounding factor in previous studies. In the present work, a functional electrophysiology assay was used to measure the recovery of dopamine-mediated D2R responsivity from antipsychotic antagonism, using elevated concentrations of dopamine to prevent the potential bias of re-binding of lipophilic ligands. The variability of antipsychotic kon was also reexamined, capitalizing on the temporal resolution of the assay. kon was estimated from the experimental recordings using a simple mathematical model assumed to describe the binding process. The time course of recovery from haloperidol (typical antipsychotic) was only 6.4- to 2.5-fold slower than that of the atypical antipsychotics, amisulpride, clozapine, and quetiapine, while antipsychotic kons were found to vary more widely than previously suggested. Finally, affinities calculated using our kon and koff estimates correlated well with functional potency and with affinities reported from radioligand binding studies. In light of these findings, it appears unlikely that typical and atypical antipsychotics are primarily distinguished by their D2R binding kinetics. PMID- 26811294 TI - Detection of genes associated with developmental competence of bovine oocytes. AB - The developmental competence of oocytes is acquired progressively during folliculogenesis and is linked to follicular size. It has been documented that oocytes originating from larger follicles exhibit a greater ability to develop to the blastocyst stage. The differences in cytoplasmic factors such as mRNA transcripts could explain the differences in oocyte developmental potential. We used bovine oligonucleotide microarrays to characterize differences between the gene expression profiles of germinal vesicle stage (GV) oocytes with greater developmental competence from medium follicles (MF) and those with less developmental competence from small follicles (SF). After normalizing the microarray data, our analysis found differences in the level of 60 transcripts (>=1.4 fold), corresponding to 49 upregulated and 11 downregulated transcripts in MF oocytes compared to SF oocytes. The gene expression data were classified according to gene ontology, the majority of the genes were associated with the regulation of transcription, translation, the cell cycle, and mitochondrial activity. A subset of 16 selected genes was validated for GV oocytes by quantitative real-time RT-PCR; significant differences (P?0.01) were found in the level of TAF1A, MTRF1L, ATP5C1, UBL5 and MAP3K13 between the MF and SF oocytes. After maturation the transcript level remained stable for ATP5F1, BRD7, and UBL5 in both oocyte categories. The transcript level of another 13 genes substantially dropped in the MF and/or SF oocytes. It can be concluded that the developmental competence of bovine oocytes and embryos may be a quantitative trait dependent on small changes in the transcription profiles of many genes. PMID- 26811295 TI - The Medically Complex Living Kidney Donor: Glucose Metabolism as Principal Cause of Donor Declination. AB - BACKGROUND: Transplant centers are increasingly confronted with medically complex living kidney donor candidates. Considerable differences exist among centers regarding handling of these patients and little data is available on characteristics, evaluation outcome and declination criteria. We now demonstrate impaired glucose metabolism to be the largest single cause of donor declination. MATERIAL AND METHODS: Follow-up of 133 donor-recipient pairs, presenting to our transplant center between 03/2007 and 06/2012 was included in the analysis. Evaluation outcome of donor-recipient pairs was assessed and declinations stratified into donor or recipient reasons and underlying conditions. RESULTS: 65 donor-recipient pairs (49%) were accepted for transplantation, 68 (51%) were declined upon first evaluation. 77% of declinations were for donor- and 23% for recipient reasons. Almost half of donor declinations resulted from increased cardiovascular risk with the presence of diabetes mellitus or prediabetes as the largest single cause of declination. CONCLUSIONS: Glucose metabolism is key in donor risk assessment and precludes kidney donation if abnormal. The high prevalence emphasizes the need for prevention. Prediabetes defines a cohort at risk and response to lifestyle intervention allows for individual risk stratification, thereby potentially increasing the number of persons eligible for kidney donation. Unification of evaluation criteria, as well as prospective long term follow-up is required to account for increasingly complex living kidney donors. PMID- 26811296 TI - Mechanisms of CPB Modified Zeolite on Mercury Adsorption in Simulated Wastewater. AB - A systematic study was carried out to analyze the effects of mercury(II) adsorption by surface modified zeolite (SMZ) and adsorption mechanism. Cetylpyridinium bromide (CPB) was used to prepare SMZ. The characterization methods by means of powder X-ray diffraction (XRD), Fourier transform infrared (FT-IR), scanning electron microscope (SEM) showed that both the surface and internal zeolite were covered with CPB molecules, but the main binding sites were surface. Results showed that the organic carbon and cation exchange capacity of the SMZ were 7.76 times and 4.22 times higher than those of natural zeolite (NZ), respectively. Zeta potentials before and after modification were measured at 7.80 mV and -30.27 mV, respectively. Moreover, the saturation adsorptive capacity of SMZ was 16.35 times higher than NZ in mercury-containing wastewater. The possible mechanisms of mercury elimination were surface adsorption, hydrophobic interaction, ion exchange, electricity neutralization. The adsorption process was affected little by competitive ions. PMID- 26811297 TI - Needle-free injection of 5-aminolevulinic acid in photodynamic therapy for the treatment of non-melanoma skin cancer. AB - BACKGROUND: Photodynamic therapy (PDT) has been widely used in treatment for skin cancer. However, topical 5-aminolevulinic acid (ALA) in PDT demonstrates poor therapeutic effect due to its shallow penetration. And intralesional ALA-PDT can bring great pain. The purpose of this study was to evaluate the efficacy of PDT with needle-free injection of ALA in the treatment of nonmalignant skin tumors. METHODS: 54 non-melanocytic malignant lesions of 54 subjects were treated with needle-free injection of 20% 5-ALA under occlusion for 1.5 hours, and irradiated with light dose of 100 J/cm(2) at 100 mW for 20 minutes. Evaluation of treatment efficacy was conducted at 2 week after treatment. RESULTS: 44 cases showed complete response with six cycles of PDT, three cases with seven cycles, and three cases with nine cycles. The remaining four cases failed to show complete response even with nine cycle of PDT. No case was reported to have recurrence in 6 months posttreatment. Only four cases experienced disease recurrence in 1 year posttreatment. CONCLUSIONS: The treatment with PDT using needle-free injection of 5-ALA appears to be effective and well tolerated with milder therapeutic pain and low recurrence rate. It can be proposed as an effective treatment alternative for non-melanoma skin cancer. PMID- 26811298 TI - Octreotide and enterocutaneous fistula closure in neonates and children. AB - Enterocutaneous fistula and its conservative management still pose a challenge for the surgeon. The use of octreotide and somatostatin in neonates and children as adjunctive therapy in the conservative management of this condition, leads to major controversy regarding its efficacy. Therefore, we conducted an extensive literature review of published articles regarding the use of somatostatin and its analogues in the treatment of enterocutaneous fistula in neonates and children. Our review is then presented together with a case vignette and discusses the different practical aspects of the treatment with these drugs. CONCLUSION: The major diversity in treatment regimens among published studies makes outcomes difficult to compare. However, given the results of the different cases reported in the literature and of our own experience, we suggest a possible beneficial effect of octreotide and somatostatin on closure of enterocutaneous fistula in these patients. PMID- 26811299 TI - Indicators of external ventricular drainage-related infections--a retrospective observational study. AB - BACKGROUND: External ventricular drainage (EVD) is frequently used in different groups of patients in neurocritical care. Despite the frequent use of EVD, no consensus regarding the diagnosis of EVD-related infection currently exists, and diagnosis is commonly based on criteria for the diagnosis of non-EVD-related CNS infections. This study evaluates the diagnostic accuracy of clinical and laboratory parameters for the prediction of EVD-related infection in patients with proven EVD-related infection. METHODS: In two tertiary care centers, data on EVD insertions were matched with a microbiologic database of cultured microorganisms and positive Gram stains of cerebrospinal fluid (CSF) to identify patients with EVD-related infections. Available clinical data and results of blood tests and CSF analysis were retrospectively collected. Predefined potential clinical and laboratory predictors of EVD-related infection were compared between three time points: at the time EVD insertion and 48 h before and at the time of occurrence of EVD-related infection. RESULTS: Thirty-nine patients with EVD associated infection defined by positive CSF culture or positive CSF Gram stains and concomitant clinical signs of infection were identified. At the time of infection, a significantly higher incidence of abnormal temperature, high respiratory rate, and a slightly but significantly higher incidence of decreased mental state were observed. The assessed blood and CSF parameters did not significantly differ between the different assessment time points. CONCLUSIONS: Our analysis of 39 patients with culture positive EVD-related infection showed that commonly used clinical and laboratory parameters are not reliable infection predictors. PMID- 26811300 TI - Treatment of high numbers of brain metastases with Gamma Knife radiosurgery: a review. AB - Effectiveness of stereotactic radiosurgery (SRS) has been shown in patients with one to four brain metastases. Work has been done to evaluate the role of SRS alone treatment without whole-brain radiation therapy in patients with more than four metastases. A recent multiinstitutional JLGK 0901 prospective study revealed the class-2 evidence that SRS without whole-brain radiation therapy is an effective treatment for patients up to 10 metastatic lesions. Several retrospective studies exist to show the efficacy and safety of SRS for patients with even more than 10 lesions. However, patient selection is very critical for SRS alone treatment. The PubMed database was searched using combinations of search terms and synonyms for multiple brain metastases, Gamma Knife and SRS published between January 1, 2005 and January 1, 2015 in order to address the effectiveness of Gamma Knife for patients with multiple brain metastases. Good performance status, controlled primary disease, total treated tumor volume of 15 cm(3) or less have been found to be significant predictors for survival among patients with two or more brain lesions. The data suggest that SRS can be used and whole brain radiation therapy can be withheld in selected patients with multiple lesions to avoid acute or chronic adverse effects, especially neurocognitive decline, without causing survival disadvantage. In this review, we assessed the evidence for SRS treatment of patients with multiple brain metastases. PMID- 26811301 TI - Parasitic twin--a supernumerary limb associated with spinal malformations. A case report. AB - We describe a case of rachipagus parasitic twin with spinal cord malformations (lipomyelomeningocele and tethered cord) in a 7-month-old Ethiopian infant. The parasitic mass had a well-formed foot, ankle and lower leg and a small sinus that resembled an anus. Magnetic resonance imaging scans revealed spinal malformations including a distal syringohydromyelia. The mass was successfully resected and the dural attachment was closed. Histopathological examination confirmed the diagnosis. Postoperatively, the child had unchanged, intact neurological function in both lower limbs. Almost all rachipagus parasitic twins are associated with spinal malformations. They should, therefore, be operated on by surgeons experienced in myelomeningocele surgery. PMID- 26811302 TI - Analysis of sinonasal anatomical variations associated with maxillary sinus fungal balls. AB - OBJECTIVE: The pathogenesis of MSFB development remains unclear, but it has been suggested that poor sinus ventilation is associated with disease development; such a ventilation is influenced by anatomical variation of the paranasal sinuses. Thus, we sought to determine whether sinonasal anatomical variations were associated with MSFB development. METHODS: Thirty-one patients with MSFB and 28 gender-matched control patients were included in the present study. The presence or absence of Haller cells and a concha bullosa were scored, and the angle of septal deviation and the minimal and maximal lengths of the infundibulum were measured on preoperative computed tomography images. RESULTS: In the MSFB group, both a concha bullosa (61.3% vs. 28.6%, p=0.006) and Haller cells (41.9% vs. 30.4%) were present at higher frequencies than in the control group, although the between-group difference in Haller cell occurrence was not statistically significant (p=0.348). In addition, MSFB patients had a significantly lower mean infundibular width (3.23+/-0.69mm vs. 3.99+/-1.17mm, p<0.001) and a longer infundibular length (9.71+/-1.43mm vs. 8.23+/-1.72mm, p<0.001) than controls. CONCLUSIONS: Sinonasal anatomical variations, especially the presence of a concha bullosa, and/or a narrow and long infundibulum, may play roles in the development of maxillary sinus fungal balls (MSFBs). PMID- 26811303 TI - Voice tuning with new instruments for type II thyroplasty in the treatment of adductor spasmodic dysphonia. AB - OBJECTIVE: Adductor spasmodic dysphonia is a rare voice disorder characterized by strained and strangled voice quality with intermittent phonatory breaks and adductory vocal fold spasms. Type II thyroplasty differs from previous treatments in that this surgery does not involve any surgical intervention into the laryngeal muscle, nerve or vocal folds. Type II thyroplasty intervenes in the thyroid cartilage, which is unrelated to the lesion. This procedure, conducted with the aim of achieving lateralization of the vocal folds, requires utmost surgical caution due to the extreme delicacy of the surgical site, critically sensitive adjustment, and difficult procedures to maintain the incised cartilages at a correct position. During surgery, the correct separation of the incised cartilage edges with voice monitoring is the most important factor determining surgical success and patient satisfaction. METHODS: We designed new surgical instruments: a thyroid cartilage elevator for undermining the thyroid cartilage, and spacer devices to gauge width while performing voice monitoring. These devices were designed to prevent surgical complications, and to aid in selecting the optimal size of titanium bridges while temporally maintaining a separation during voice monitoring. RESULTS: We designed new surgical instruments, including a thyroid cartilage elevator and spacer devices. Precise surgical procedures and performing voice tuning during surgery with the optimal separation width of the thyroid cartilage are key points for surgical success. CONCLUSION: We introduce the technique of voice tuning using these surgical tools in order to achieve a better outcome with minimal surgical complications. PMID- 26811304 TI - Torsion of omental fibrous pseudotumour mimicking acute appendicitis. AB - Unusual pathologies are occasionally found at laparoscopy when appendicitis is suspected. We present a case of strangulated inflammatory fibrous pseudotumour of the omentum presenting in a similar fashion to appendicitis. The infarcted omentum was excised, facilitating prompt resolution of symptoms. PMID- 26811305 TI - Distribution of Force in the Medial Collateral Ligament Complex During Simulated Clinical Tests of Knee Stability. AB - BACKGROUND: Pivot-shift injury commonly results in combined anterior cruciate ligament (ACL)/medial collateral ligament (MCL) injury, yet the contribution of the components of the MCL complex to restraining multiplanar rotatory loads forming critical subcomponents of the pivot shift is not well understood. PURPOSE: To quantify the role of the MCL complex in restraining multiplanar rotatory loads. STUDY DESIGN: Controlled laboratory study. METHODS: A robotic manipulator was used to apply combined valgus and internal rotation torques in a simplified model of the pivot-shift examination in 12 cadaveric knees (49 +/- 11 years). Tibiofemoral kinematics were recorded with the ACL intact. Loads borne by the superficial MCL (sMCL), posterior oblique ligament (POL), deep MCL (dMCL), and ACL were determined via the principle of superposition. RESULTS: The POL bore about 50% of the load carried by the ACL in response to the combined torques at 5 degrees and 15 degrees of flexion. The POL bore load during the internal rotation component of the combined torques, while the sMCL carried load during the valgus and internal rotation phases of the simulated pivot. Load in the dMCL was always <10% of the ACL in response to combined valgus and internal rotation torques. CONCLUSION: The POL provides complementary load bearing to the ACL near extension in response to combined torques, which capture key components of the pivot-shift examination. The sMCL resists the valgus component of the maneuver alone, a loading pattern unique from those of the POL and ACL. The dMCL is not loaded during clinical tests of rotational knee stability in the ACL-competent knee. CLINICAL RELEVANCE: Both the sMCL and POL work together with the ACL to resist combined moments, which form key components of the pivot-shift examination. PMID- 26811306 TI - Structural Properties of the Anterolateral Capsule and Iliotibial Band of the Knee. AB - BACKGROUND: The role of the anterolateral capsule in knee stability has recently been advocated by studies reporting that a distinct ligament exists in this area. Defining the structural properties of the anterolateral capsule can provide insight into its contribution to joint stability. The structural properties of the iliotibial band also need to be determined, as it is a common graft used for extra-articular tenodesis. PURPOSE/HYPOTHESIS: The purpose of this study was to determine the structural properties of the anterolateral capsule and iliotibial band. The hypothesis was that the iliotibial band will have comparable structural properties to the anterolateral capsule because it is generally an accepted graft for extra-articular reconstruction surgeries. STUDY DESIGN: Controlled laboratory study. METHODS: Nine human cadaveric knees (average age, 57 +/- 10 years) were dissected to assess the presence of a discrete capsular thickness originating from the lateral femoral epicondyle to the lateral tibial plateau between the Gerdy tubercle and the fibular head. For each knee, 2 constructs were prepared: (1) a bone-anterolateral capsule-bone specimen and (2) a strip of iliotibial band attached to the Gerdy tubercle. Structural properties, including ultimate load, ultimate elongation, and stiffness, were determined for the anterolateral capsule and the iliotibial band. After tensile testing, plain radiographs were obtained for evaluation of the Segond fracture. A paired t test was used to compare the structural properties of the anterolateral capsule with the iliotibial band. Significance was set at P < .05. RESULTS: Two of the 9 specimens were found to have a discrete thickening of the anterolateral capsule. The iliotibial band had almost 50% higher ultimate load and nearly 3 times higher stiffness (487.9 +/- 156.9 N and 73.2 +/- 24.1 N/mm, respectively) compared with the anterolateral capsule (319.7 +/- 212.6 N and 26.0 +/- 11.5 N/mm, respectively) (P < .05 for both). The anterolateral capsule had about double the ultimate elongation compared with the iliotibial band (15.5 +/- 7.3 and 8.6 +/- 1.4 mm, respectively; P < .05). CONCLUSION: The anterolateral capsule demonstrated significantly reduced structural properties compared with the iliotibial band. The anterolateral capsule did not have a higher ultimate load compared with the posteromedial capsule as reported in the literature. CLINICAL RELEVANCE: The decision to perform an extra-articular reconstruction using an iliotibial band graft should be considered carefully. Unnecessary reconstructions using soft tissue grafts with structural properties that far exceed that of the anterolateral capsule may result in overconstraint of the ACL-reconstructed knee. PMID- 26811307 TI - Statistics. PMID- 26811308 TI - Commentary on Long-term clinical outcome after epineural coaptation of digital nerves. R. M. Fakin, M. Calcagni, H. J. Klein and P. Giovanoli. J Hand Surg. 2016, 41: 148-154. PMID- 26811309 TI - Re: Knight R, Pagkalos J, Timmons C et al. Caffeine consumption does not have an effect on digital microvascular perfusion assessed by laser Doppler imaging on healthy volunteers: a pilot study. J Hand Surg Eur. 2015, 40: 412-5. PMID- 26811312 TI - Cocaine-induced behavioral sensitization decreases the expression of endocannabinoid signaling-related proteins in the mouse hippocampus. AB - In the reward mesocorticolimbic circuits, the glutamatergic and endocannabinoid systems are implicated in neurobiological mechanisms underlying cocaine addiction. However, the involvement of both systems in the hippocampus, a critical region to process relational information relevant for encoding drug associated memories, in cocaine-related behaviors remains unknown. In the present work, we studied whether the hippocampal gene/protein expression of relevant glutamate signaling components, including glutamate-synthesizing enzymes and metabotropic and ionotropic receptors, and the hippocampal gene/protein expression of cannabinoid type 1 (CB1) receptor and endocannabinoid metabolic enzymes were altered following acute and/or repeated cocaine administration resulting in conditioned locomotion and locomotor sensitization. Results showed that acute cocaine administration induced an overall down-regulation of glutamate related gene expression and, specifically, a low phosphorylation level of GluA1. In contrast, locomotor sensitization to cocaine produced an up-regulation of several glutamate receptor-related genes and, specifically, an increased protein expression of the GluN1 receptor subunit. Regarding the endocannabinoid system, acute and repeated cocaine administration were associated with an increased gene/protein expression of CB1 receptors and a decreased gene/protein expression of the endocannabinoid-synthesis enzymes N-acyl phosphatidylethanolamine D (NAPE PLD) and diacylglycerol lipase alpha (DAGLalpha). These changes resulted in an overall decrease in endocannabinoid synthesis/degradation ratios, especially NAPE PLD/fatty acid amide hydrolase and DAGLalpha/monoacylglycerol lipase, suggesting a reduced endocannabinoid production associated with a compensatory up-regulation of CB1 receptor. Overall, these findings suggest that repeated cocaine administration resulting in locomotor sensitization induces a down-regulation of the endocannabinoid signaling that could contribute to the specifically increased GluN1 expression observed in the hippocampus of cocaine-sensitized mice. PMID- 26811314 TI - Reproductive organ and young tissues show constrained elemental composition in Arabidopsis thaliana. AB - BACKGROUND AND AIMS: The identification of stoichiometric homeostasis is crucial for understanding plant adaptive strategies under a changing environment. However, current knowledge of plant stoichiometric homeostasis has mainly been obtained from mature leaves, with little from other organs across different developmental stages. METHODS: We conducted a greenhouse nitrogen (N) and phosphorus (P) addition experiment to evaluate the strength of stoichiometric homeostasis across different organs and developmental stages of Arabidopsis thaliana. KEY RESULTS: Homeostatic regulation coefficients (H) for N (HN), P (HP) and N : P ratio (HNP) were highest in reproductive tissue, followed by stem and leaf at the same stage. All H parameters in the same organ decreased significantly over the developmental stages. Leaf HN, HP and HNP were highest at stage 1, followed by stages 2 and 3. Both stem and silique at stage 2 relative to stage 3 had higher HN, HP and HNP. These results suggested that reproductive tissue relative to other organs and young tissue relative to old tissue showed more constrained elemental composition in response to nutrient availabilities, and such trends were also evidenced by stoichiometric scaling relationships. CONCLUSIONS: Our findings highlight that stoichiometric homeostasis is tightly related to the ontogenesis of plant tissue. These results could have a strong implication for diagnosing relative availabilities of N and P in ecosystems, suggesting that the N and P stoichiometry of old tissues might be stronger indicators of nutrient status for plants, but further study is needed to test the generality across species with more distinguishable functional traits. PMID- 26811313 TI - Hepatic Metastases is Associated with Poor Efficacy of Erlotinib as 2nd/3rd Line Therapy in Patients with Lung Adenocarcinoma. AB - BACKGROUND: Hepatocyte growth factor (HGF)-mediated mesenchymal-to-epithelial transition factor (MET) gene amplification is a common mechanism for acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs). MET gene amplification has also been associated with hepatic metastases in patients with lung cancer. The aim of this study was to investigate whether hepatic metastases are associated with decreased efficacy of erlotinib in patients with adenocarcinoma. MATERIAL/METHODS: A cohort of 329 patients with stage IV lung adenocarcinoma, known EGFR mutation status, and who received treatment with erlotinib in the 2nd or 3rd line setting were enrolled into this study over a period of 4 years between January 2011 and January 2015. The cohort was stratified based on the presence or absence of hepatic metastases and the efficacy of erlotinib was defined based on disease control rate (DCR) and progression-free survival (PFS). RESULTS: Hepatic metastases were present in 220 of the 329 enrolled lung adenocarcinoma patients. EGFR-activating mutations (exon 19 deletion or an exon 21 L858R mutation) were identified in 113 (34.3%) patients. The DCR was significantly lower in the hepatic metastases group than in patients without hepatic metastases (39.5% vs. 51.4% P=0.045). In patients with hepatic metastases, median PFS was 2.3 months in the EGFR mutation-positive group versus 1.4 months in the EGFR mutation-negative group (95% CI 1.3-3.3 vs. 1.3 1.5; P=0.055). Of note, erlotinib therapy in patients with hepatic metastases was complicated by elevated alanine transaminase (ALT) levels. CONCLUSIONS: Hepatic metastasis in patients with lung adenocarcinoma predicts poor response to erlotinib as a 2nd/3rd line therapy. Combination therapy, for example with MET TKI, may be a good choice for patients with liver metastases with poor prognosis. PMID- 26811315 TI - Maltreatment and Emotional and Behavioral Problems in Chinese Children With and Without Oppositional Defiant Disorder: The Mediating Role of the Parent-Child Relationship. AB - Maltreatment has negative effects on the parent-child relationship and the emotional and behavioral development of children. The current study aimed to examine the associations among maltreatment, parent-child relationship, and emotional and behavioral problems in Chinese children with or without oppositional defiant disorder (ODD). Participants in the study included 259 children with ODD and their 269 non-ODD counterparts from northern, eastern, and southwestern China. We also collected data from their teachers and fathers or mothers. The results showed that ODD children suffered more maltreatment and had more emotional and behavioral problems than their non-ODD peers. For all children (both ODD and non-ODD children), emotional abuse predicted emotional problems but not behavioral problems. Physical abuse predicted behavioral problems but not emotional problems. Parent-child relationship mediated the effects of emotional abuse and physical abuse on emotional problems among ODD children but not among non-ODD children. Implications for prevention of emotional and physical abuse and ODD in the Chinese cultural context are discussed. PMID- 26811316 TI - Acute Myocardial Infarction in Women: A Scientific Statement From the American Heart Association. AB - Cardiovascular disease is the leading cause of mortality in American women. Since 1984, the annual cardiovascular disease mortality rate has remained greater for women than men; however, over the last decade, there have been marked reductions in cardiovascular disease mortality in women. The dramatic decline in mortality rates for women is attributed partly to an increase in awareness, a greater focus on women and cardiovascular disease risk, and the increased application of evidence-based treatments for established coronary heart disease. This is the first scientific statement from the American Heart Association on acute myocardial infarction in women. Sex-specific differences exist in the presentation, pathophysiological mechanisms, and outcomes in patients with acute myocardial infarction. This statement provides a comprehensive review of the current evidence of the clinical presentation, pathophysiology, treatment, and outcomes of women with acute myocardial infarction. PMID- 26811317 TI - SrrAB Modulates Staphylococcus aureus Cell Death through Regulation of cidABC Transcription. AB - The death and lysis of a subpopulation in Staphylococcus aureus biofilm cells are thought to benefit the surviving population by releasing extracellular DNA, a critical component of the biofilm extracellular matrix. Although the means by which S. aureus controls cell death and lysis is not understood, studies implicate the role of the cidABC and lrgAB operons in this process. Recently, disruption of the srrAB regulatory locus was found to cause increased cell death during biofilm development, likely as a result of the sensitivity of this mutant to hypoxic growth. In the current study, we extended these findings by demonstrating that cell death in the DeltasrrAB mutant is dependent on expression of the cidABC operon. The effect of cidABC expression resulted in the generation of increased reactive oxygen species (ROS) accumulation and was independent of acetate production. Interestingly, consistently with previous studies, cidC encoded pyruvate oxidase was found to be important for the generation of acetic acid, which initiates the cell death process. However, these studies also revealed for the first time an important role of the cidB gene in cell death, as disruption of cidB in the DeltasrrAB mutant background decreased ROS generation and cell death in a cidC-independent manner. The cidB mutation also caused decreased sensitivity to hydrogen peroxide, which suggests a complex role for this system in ROS metabolism. Overall, the results of this study provide further insight into the function of the cidABC operon in cell death and reveal its contribution to the oxidative stress response. IMPORTANCE: The manuscript focuses on cell death mechanisms in Staphylococcus aureus and provides important new insights into the genes involved in this ill-defined process. By exploring the cause of increased stationary-phase death in an S. aureus DeltasrrAB regulatory mutant, we found that the decreased viability of this mutant was a consequence of the overexpression of the cidABC operon, previously shown to be a key mediator of cell death. These investigations highlight the role of the cidB gene in the death process and the accumulation of reactive oxygen species. Overall, the results of this study are the first to demonstrate a positive role for CidB in cell death and to provide an important paradigm for understanding this process in all bacteria. PMID- 26811318 TI - Small RNA Regulation of TolC, the Outer Membrane Component of Bacterial Multidrug Transporters. AB - Bacteria use multidrug efflux pumps to export drugs and toxic compounds out of the cell. One of the most important efflux pumps in Escherichia coli is the AcrAB TolC system. Small regulatory RNAs (sRNAs) are known to be major posttranscriptional regulators that can enhance or repress translation by binding to the 5' untranslated region (UTR) of mRNA targets with the help of a chaperone protein, Hfq. In this study, we investigated the expression of acrA, acrB, and tolC translational fusions using 27 Hfq-dependent sRNAs overexpressed from plasmids. No significant sRNA regulation of acrA or acrB was detected. SdsR (also known as RyeB), an abundant and well-conserved stationary-phase sRNA, was found to repress the expression of tolC, the gene encoding the outer membrane protein of many multidrug resistance efflux pumps. This repression was shown to be by direct base pairing occurring upstream from the ribosomal binding site. SdsR overexpression and its regulation of tolC were found to reduce resistance to novobiocin and crystal violet. Our results suggest that additional targets for SdsR exist that contribute to increased antibiotic sensitivity and reduced biofilm formation. In an effort to identify phenotypes associated with single copy SdsR and its regulation of tolC, the effect of a deletion of sdsR or mutations in tolC that should block SdsR pairing were investigated using a Biolog phenotypic microarray. However, no significant phenotypes were identified. Therefore, SdsR appears to modulate rather than act as a major regulator of its targets. IMPORTANCE: AcrAB-TolC is a major efflux pump present in E. coli and Gram-negative bacteria used to export toxic compounds; the pump confers resistance to many antibiotics of unrelated classes. In this study, we found that SdsR, a small RNA expressed in stationary phase, repressed the expression of tolC, resulting in increased sensitivity to some antibiotics. This extends the findings of previous studies showing that sRNAs contribute to the regulation of many outer membrane proteins; manipulating or enhancing their action might help in sensitizing bacteria to antibiotics. PMID- 26811319 TI - SagB Glucosaminidase Is a Determinant of Staphylococcus aureus Glycan Chain Length, Antibiotic Susceptibility, and Protein Secretion. AB - The envelope of Staphylococcus aureus is comprised of peptidoglycan and its attached secondary polymers, teichoic acid, capsular polysaccharide, and protein. Peptidoglycan synthesis involves polymerization of lipid II precursors into glycan strands that are cross-linked at wall peptides. It is not clear whether peptidoglycan structure is principally determined during polymerization or whether processive enzymes affect cell wall structure and function, for example, by generating conduits for protein secretion. We show here that S. aureus lacking SagB, a membrane-associated N-acetylglucosaminidase, displays growth and cell morphological defects caused by the exaggerated length of peptidoglycan strands. SagB cleaves polymerized glycan strands to their physiological length and modulates antibiotic resistance in methicillin-resistant S. aureus (MRSA). Deletion of sagB perturbs protein trafficking into and across the envelope, conferring defects in cell wall anchoring and secretion, as well as aberrant excretion of cytoplasmic proteins. IMPORTANCE: Staphylococcus aureus is thought to secrete proteins across the plasma membrane via the Sec pathway; however, protein transport across the cell wall envelope has heretofore not been studied. We report that S. aureus sagB mutants generate elongated peptidoglycan strands and display defects in protein secretion as well as aberrant excretion of cytoplasmic proteins. These results suggest that the thick peptidoglycan layer of staphylococci presents a barrier for protein secretion and that SagB appears to extend the Sec pathway across the cell wall envelope. PMID- 26811320 TI - Mutation of the murC and murB Genes Impairs Heterocyst Differentiation in Anabaena sp. Strain PCC 7120. AB - To stabilize cellular integrity in the face of environmental perturbations, most bacteria, including cyanobacteria, synthesize and maintain a strong, flexible, three-dimensional peptidoglycan lattice. Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium capable of differentiating morphologically distinct nitrogen-fixing heterocyst cells in a periodic pattern. While heterocyst development has been shown to require proper peptidoglycan remodeling, the role of peptidoglycan synthesis has remained unclear. Here we report the identification of two peptidoglycan synthesis genes, murC (alr5065) and murB (alr5066), as required for heterocyst development. The murC and murB genes are predicted to encode a UDP-N-acetylmuramate:L-alanine ligase and a UDP-N acetylenolpyruvoylglucosamine reductase, respectively, and we confirm enzymatic function through complementation of Escherichia coli strains deficient for these enzymes. Cells depleted of either murC or murB expression failed to differentiate heterocysts under normally inducing conditions and displayed decreased filament integrity. To identify the stage(s) of development affected by murC or murB depletion, the spatial distribution of expression of the patterning marker gene, patS, was examined. Whereas murB depletion did not affect the pattern of patS expression, murC depletion led to aberrant expression of patS in all cells of the filament. Finally, expression of gfp controlled by the region of DNA immediately upstream of murC was enriched in differentiating cells and was repressed by the transcription factor NtcA. Collectively, the data in this work provide evidence for a direct link between peptidoglycan synthesis and the maintenance of a biological pattern in a multicellular organism. IMPORTANCE: Multicellular organisms that differentiate specialized cells must regulate morphological changes such that both cellular integrity and the dissemination of developmental signals are preserved. Here we show that the multicellular bacterium Anabaena, which differentiates a periodic pattern of specialized heterocyst cells, requires peptidoglycan synthesis by the murine ligase genes murC (alr5065) and murB (alr5066) for maintenance of patterned gene expression, filament integrity, and overall development. This work highlights the significant influence that intracellular structure and intercellular connections can have on the execution of a developmental program. PMID- 26811322 TI - Estimating Occupational Exposure to Asbestos in Australia. PMID- 26811323 TI - Disease Control Among Patients With Diabetes and Severe Depressive Symptoms. AB - OBJECTIVE: Major depressive disorder and type 2 diabetes commonly co-occur and disease control tends to be poorer when both conditions are present. However, little research has examined the disease characteristics of patients with diabetes and more severe depressive symptoms. METHODS: We report a retrospective observational study of 517 patients with diabetes from 2 primary care centers. Patients with diabetes and moderately-severe/severe depression symptoms (Patient Health Questionnaire [PHQ-9] score >15) were compared with patients with diabetes without moderate or severe depression symptoms (PHQ-9 score <15; the comparison group) with regard to control of diabetes, blood pressure, and lipid parameters. Frequency of HbA1c and PHQ-9 testing were also examined. RESULTS: Patients with diabetes and moderately severe/severe depressive symptoms had higher HbA1c (7.56% vs. 7.09%), diastolic blood pressure (78.43 vs. 75.67 mm Hg), and low-density lipoprotein cholesterol (109.12 vs. 94.22 mg/dL) versus the comparison group. Patients with diabetes and moderately-severe/severe depression underwent HbA1c and PHQ-9 testing with similar frequency to the comparison group. CONCLUSIONS: The presence of moderately severe/severe depressive symptoms was associated with poorer glucose, lipid, and blood pressure control among patients with diabetes. Further research should prospectively examine whether a targeted depression treatment goal (PHQ-9 score <15) in patients with diabetes results in improved control of these important disease parameters. PMID- 26811321 TI - Trk2 Potassium Transport System in Streptococcus mutans and Its Role in Potassium Homeostasis, Biofilm Formation, and Stress Tolerance. AB - Potassium (K(+)) is the most abundant cation in the fluids of dental biofilm. The biochemical and biophysical functions of K(+) and a variety of K(+) transport systems have been studied for most pathogenic bacteria but not for oral pathogens. In this study, we establish the modes of K(+) acquisition in Streptococcus mutans and the importance of K(+) homeostasis for its virulence attributes. The S. mutans genome harbors four putative K(+) transport systems that included two Trk-like transporters (designated Trk1 and Trk2), one glutamate/K(+) cotransporter (GlnQHMP), and a channel-like K(+) transport system (Kch). Mutants lacking Trk2 had significantly impaired growth, acidogenicity, aciduricity, and biofilm formation. [K(+)] less than 5 mM eliminated biofilm formation in S. mutans. The functionality of the Trk2 system was confirmed by complementing an Escherichia coli TK2420 mutant strain, which resulted in significant K(+) accumulation, improved growth, and survival under stress. Taken together, these results suggest that Trk2 is the main facet of the K(+)-dependent cellular response of S. mutans to environment stresses. IMPORTANCE: Biofilm formation and stress tolerance are important virulence properties of caries causing Streptococcus mutans. To limit these properties of this bacterium, it is imperative to understand its survival mechanisms. Potassium is the most abundant cation in dental plaque, the natural environment of S. mutans. K(+) is known to function in stress tolerance, and bacteria have specialized mechanisms for its uptake. However, there are no reports to identify or characterize specific K(+) transporters in S. mutans. We identified the most important system for K(+) homeostasis and its role in the biofilm formation, stress tolerance, and growth. We also show the requirement of environmental K(+) for the activity of biofilm forming enzymes, which explains why such high levels of K(+) would favor biofilm formation. PMID- 26811324 TI - Pembrolizumab Outperforms Docetaxel for NSCLC. PMID- 26811326 TI - Benefit Finding in Maternal Caregivers of Pediatric Cancer Survivors: A Mixed Methods Approach. AB - OBJECTIVE: Benefit finding has been described as the identification of positive effects resulting from otherwise stressful experiences. In this mixed methods study, we examined the relations between qualitative themes related to benefit finding and quantitative measures of psychosocial adjustment and coping as reported by maternal caregivers of survivors of pediatric cancer. METHODS: Female caregivers of survivors of pediatric cancer (n = 40) completed a qualitative questionnaire about their experiences caring for their child, along with several quantitative measures. Qualitative questionnaires were coded for salient themes, including social support and personal growth. Correlation matrices evaluated associations between qualitative themes and quantitative measures of stress and coping. RESULTS: Identified benefits included social support and personal growth, as well as child-specific benefits. Total benefits reported were significantly positively correlated with availability of emotional resources. Coping methods were also associated, with accepting responsibility associated with fewer identified benefits. CONCLUSION: Despite the stress of their child's illness, many female caregivers of survivors of pediatric cancer reported finding benefits associated with their experience. Benefit finding in this sample was associated with better adjustment. PMID- 26811325 TI - Tumor Cell-Driven Extracellular Matrix Remodeling Drives Haptotaxis during Metastatic Progression. AB - Fibronectin (FN) is a major component of the tumor microenvironment, but its role in promoting metastasis is incompletely understood. Here, we show that FN gradients elicit directional movement of breast cancer cells, in vitro and in vivo Haptotaxis on FN gradients requires direct interaction between alpha5beta1 integrin and MENA, an actin regulator, and involves increases in focal complex signaling and tumor cell-mediated extracellular matrix (ECM) remodeling. Compared with MENA, higher levels of the prometastatic MENA(INV) isoform associate with alpha5, which enables 3-D haptotaxis of tumor cells toward the high FN concentrations typically present in perivascular space and in the periphery of breast tumor tissue. MENA(INV) and FN levels were correlated in two breast cancer cohorts, and high levels of MENA(INV) were significantly associated with increased tumor recurrence as well as decreased patient survival. Our results identify a novel tumor cell-intrinsic mechanism that promotes metastasis through ECM remodeling and ECM-guided directional migration. SIGNIFICANCE: Here, we provide new insight into how tumor cell:ECM interactions generate signals and structures that promote directed tumor cell migration, a critical component of metastasis. Our results identify a tumor cell-intrinsic mechanism driven by the actin regulatory protein MENA that promotes ECM remodeling and haptotaxis along FN gradients. Cancer Discov; 6(5); 516-31. (c)2016 AACR.See related commentary by Santiago-Medina and Yang, p. 474This article is highlighted in the In This Issue feature, p. 461. PMID- 26811327 TI - Type I Interferons Control Proliferation and Function of the Intestinal Epithelium. AB - Wnt pathway-driven proliferation and renewal of the intestinal epithelium must be tightly controlled to prevent development of cancer and barrier dysfunction. Although type I interferons (IFN) produced in the gut under the influence of microbiota are known for their antiproliferative effects, the role of these cytokines in regulating intestinal epithelial cell renewal is largely unknown. Here we report a novel role for IFN in the context of intestinal knockout of casein kinase 1alpha (CK1alpha), which controls the ubiquitination and degradation of both beta-catenin and the IFNAR1 chain of the IFN receptor. Ablation of CK1alpha leads to the activation of both beta-catenin and IFN pathways and prevents the unlimited proliferation of intestinal epithelial cells despite constitutive beta-catenin activity. IFN signaling contributes to the activation of the p53 pathway and the appearance of apoptotic and senescence markers in the CK1alpha-deficient gut. Concurrent genetic ablation of CK1alpha and IFNAR1 leads to intestinal hyperplasia, robust attenuation of apoptosis, and rapid and lethal loss of barrier function. These data indicate that IFN play an important role in controlling the proliferation and function of the intestinal epithelium in the context of beta-catenin activation. PMID- 26811328 TI - Evolution and Functional Trajectory of Sir1 in Gene Silencing. AB - We used the budding yeasts Saccharomyces cerevisiae and Torulaspora delbrueckii to examine the evolution of Sir-based silencing, focusing on Sir1, silencers, the molecular topography of silenced chromatin, and the roles of SIR and RNA interference (RNAi) genes in T. delbrueckii. Chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) analysis of Sir proteins in T. delbrueckii revealed a different topography of chromatin at the HML and HMR loci than was observed in S. cerevisiae. S. cerevisiae Sir1, enriched at the silencers of HMLalpha and HMR A: , was absent from telomeres and did not repress subtelomeric genes. In contrast to S. cerevisiae SIR1's partially dispensable role in silencing, the T. delbrueckii SIR1 paralog KOS3 was essential for silencing. KOS3 was also found at telomeres with T. delbrueckii Sir2 (Td-Sir2) and Td-Sir4 and repressed subtelomeric genes. Silencer mapping in T. delbrueckii revealed single silencers at HML and HMR, bound by Td-Kos3, Td-Sir2, and Td-Sir4. The KOS3 gene mapped near HMR, and its expression was regulated by Sir-based silencing, providing feedback regulation of a silencing protein by silencing. In contrast to the prominent role of Sir proteins in silencing, T. delbrueckii RNAi genes AGO1 and DCR1 did not function in heterochromatin formation. These results highlighted the shifting role of silencing genes and the diverse chromatin architectures underlying heterochromatin. PMID- 26811329 TI - GGA3 Interacts with a G Protein-Coupled Receptor and Modulates Its Cell Surface Export. AB - Molecular mechanisms governing the anterograde trafficking of nascent G protein coupled receptors (GPCRs) are poorly understood. Here, we have studied the regulation of cell surface transport of alpha2-adrenergic receptors (alpha2-ARs) by GGA3 (Golgi-localized, gamma-adaptin ear domain homology, ADP ribosylation factor-binding protein 3), a multidomain clathrin adaptor protein that sorts cargo proteins at the trans-Golgi network (TGN) to the endosome/lysosome pathway. By using an inducible system, we demonstrated that GGA3 knockdown significantly inhibited the cell surface expression of newly synthesized alpha2B-AR without altering overall receptor synthesis and internalization. The receptors were arrested in the TGN. Furthermore, GGA3 knockdown attenuated alpha2B-AR-mediated signaling, including extracellular signal-regulated kinase 1/2 (ERK1/2) activation and cyclic AMP (cAMP) inhibition. More interestingly, GGA3 physically interacted with alpha2B-AR, and the interaction sites were identified as the triple Arg motif in the third intracellular loop of the receptor and the acidic motif EDWE in the VHS domain of GGA3. In contrast, alpha2A-AR did not interact with GGA3 and its cell surface export and signaling were not affected by GGA3 knockdown. These data reveal a novel function of GGA3 in export trafficking of a GPCR that is mediated via a specific interaction with the receptor. PMID- 26811332 TI - Correction. World Stroke Organization. Stroke and potentially preventable dementias proclamation: updated World Stroke Day proclamation. PMID- 26811330 TI - Fas-Associated Factor 1 Negatively Regulates the Antiviral Immune Response by Inhibiting Translocation of Interferon Regulatory Factor 3 to the Nucleus. AB - This study is designed to examine the cellular functions of human Fas-associated factor 1 (FAF1) containing multiple ubiquitin-related domains. Microarray analyses revealed that interferon-stimulated genes related to the antiviral response are significantly increased in FAF1-knockdown HeLa cells. Silencing FAF1 enhanced the poly(I.C)- and respiratory syncytial virus (RSV)-induced production of type I interferons (IFNs), the target genes of interferon regulator factor 3 (IRF3). IRF3 is a key transcription factor in IFN-beta signaling responsible for the host innate immune response. This study also found that FAF1 and IRF3 physically associate with IPO5/importin-beta3 and that overexpression of FAF1 reduces the interaction between IRF3 and IPO5/importin-beta3. These findings suggest that FAF1 negatively regulates IRF3-mediated IFN-beta production and the antiviral innate immune response by regulating nuclear translocation of IRF3. We conclude that FAF1 plays a novel role in negatively regulating virus-induced IFN beta production and the antiviral response by inhibiting the translocation of active, phosphorylated IRF3 from the cytosol to the nucleus. PMID- 26811333 TI - Correction. SMART Study Group. Cerebellar cortical infarct cavities: correlation with risk factors and MRI markers of cerebrovascular disease. PMID- 26811334 TI - Correction. Early detection and quantification of cerebral venous thrombosis by magnetic resonance blackblood thrombus imaging. PMID- 26811335 TI - Analysis of Immune Cells from Human Mammary Ductal Epithelial Organoids Reveals Vdelta2+ T Cells That Efficiently Target Breast Carcinoma Cells in the Presence of Bisphosphonate. AB - Developing strategies to enhance cancer prevention is a paramount goal, particularly given recent concerns about surgical treatment of preinvasive states such as ductal carcinoma in situ. Promoting effective immunosurveillance by leukocytes that scan for nascent neoplastic transformations represents a potential means to achieve this goal. Because most breast cancers arise within the ductal epithelium, enhancing protective immunosurveillance will likely necessitate targeting one or more of the distinctive lymphocyte types found in these sites under normal conditions. Here, we have characterized the intraepithelial lymphocyte compartment of non-cancerous human breast tissue and identified a subset of T lymphocytes that can be pharmacologically targeted to enhance their responses to breast cancer cells. Specifically, Vdelta2(+) gammadelta T cells were consistently present in preparations of mammary ductal epithelial organoids and they proliferated in response to zoledronic acid, an aminobisphosphonate drug. Vdelta2(+) T cells from breast ductal organoids produced the antitumor cytokine IFNgamma and efficiently killed bisphosphonate pulsed breast carcinoma cells. These findings demonstrate the potential for exploiting the ability of Vdelta2(+) gammadelta T cells to respond to FDA approved bisphosphonate drugs as a novel immunotherapeutic approach to inhibit the outgrowth of breast cancers. PMID- 26811336 TI - A Human Disease-causing Point Mutation in Mitochondrial Threonyl-tRNA Synthetase Induces Both Structural and Functional Defects. AB - Mitochondria require all translational components, including aminoacyl-tRNA synthetases (aaRSs), to complete organelle protein synthesis. Some aaRS mutations cause mitochondrial disorders, including human mitochondrial threonyl-tRNA synthetase (hmtThrRS) (encoded by TARS2), the P282L mutation of which causes mitochondrial encephalomyopathies. However, its catalytic and structural consequences remain unclear. Herein, we cloned TARS2 and purified the wild-type and P282L mutant hmtThrRS. hmtThrRS misactivates non-cognate Ser and uses post transfer editing to clear erroneously synthesized products. In vitro and in vivo analyses revealed that the mutation induces a decrease in Thr activation, aminoacylation, and proofreading activities and a change in the protein structure and/or stability, which might cause reduced catalytic efficiency. We also identified a splicing variant of TARS2 mRNA lacking exons 8 and 9, the protein product of which is targeted into mitochondria. In HEK293T cells, the variant does not dimerize and cannot complement the ThrRS knock-out strain in yeast, suggesting that the truncated protein is inactive and might have a non-canonical function, as observed for other aaRS fragments. The present study describes the aminoacylation and editing properties of hmtThrRS, clarifies the molecular consequences of the P282L mutation, and shows that the yeast ThrRS-deletion model is suitable to test pathology-associated point mutations or alternative splicing variants of mammalian aaRS mRNAs. PMID- 26811337 TI - Low pH and Anionic Lipid-dependent Fusion of Uukuniemi Phlebovirus to Liposomes. AB - Many phleboviruses (family Bunyaviridae) are emerging as medically important viruses. These viruses enter target cells by endocytosis and low pH-dependent membrane fusion in late endosomes. However, the necessary and sufficient factors for fusion have not been fully characterized. We have studied the minimal fusion requirements of a prototypic phlebovirus, Uukuniemi virus, in an in vitro virus liposome assay. We show that efficient lipid mixing between viral and liposome membranes requires close to physiological temperatures and phospholipids with negatively charged headgroups, such as the late endosomal phospholipid bis(monoacylglycero)phosphate. We further demonstrate that bis(monoacylglycero)phosphate increases Uukuniemi virus fusion beyond the lipid mixing stage. By using electron cryotomography of viral particles in the presence or absence of liposomes, we observed that the conformation of phlebovirus glycoprotein capsomers changes from the native conformation toward a more elongated conformation at a fusion permissive pH. Our results suggest a rationale for phlebovirus entry in late endosomes. PMID- 26811338 TI - Association with the Plasma Membrane Is Sufficient for Potentiating Catalytic Activity of Regulators of G Protein Signaling (RGS) Proteins of the R7 Subfamily. AB - Regulators of G protein Signaling (RGS) promote deactivation of heterotrimeric G proteins thus controlling the magnitude and kinetics of responses mediated by G protein-coupled receptors (GPCR). In the nervous system, RGS7 and RGS9-2 play essential role in vision, reward processing, and movement control. Both RGS7 and RGS9-2 belong to the R7 subfamily of RGS proteins that form macromolecular complexes with R7-binding protein (R7BP). R7BP targets RGS proteins to the plasma membrane and augments their GTPase-accelerating protein (GAP) activity, ultimately accelerating deactivation of G protein signaling. However, it remains unclear if R7BP serves exclusively as a membrane anchoring subunit or further modulates RGS proteins to increase their GAP activity. To directly answer this question, we utilized a rapidly reversible chemically induced protein dimerization system that enabled us to control RGS localization independent from R7BP in living cells. To monitor kinetics of Galpha deactivation, we coupled this strategy with measuring changes in the GAP activity by bioluminescence resonance energy transfer-based assay in a cellular system containing MU-opioid receptor. This approach was used to correlate changes in RGS localization and activity in the presence or absence of R7BP. Strikingly, we observed that RGS activity is augmented by membrane recruitment, in an orientation independent manner with no additional contributions provided by R7BP. These findings argue that the association of R7 RGS proteins with the membrane environment provides a major direct contribution to modulation of their GAP activity. PMID- 26811340 TI - Synergistic Benefit of Statin and Metformin in Gastrointestinal Malignancies. AB - OBJECTIVES: To evaluate whether statin use influences gastrointestinal cancer prognosis in patients with diabetes mellitus (DM). METHODS: We reviewed all DM patients diagnosed at Roswell Park Cancer Institute with emergent gastrointestinal malignancy (January 2003 to December 2010) (N = 222). Baseline demographic, clinical history, and cancer outcomes were documented. Overall survival (OS) and disease-free survival (DFS) comparisons across various treatment groups were assessed by Kaplan-Meier and Cox proportional hazards. RESULTS: Use of statin, alone or in combination, was associated with improved OS and DFS (hazard ratio [HR] = 0.65, P = .06; HR = 0.60, P < .02). We report similar OS and DFS advantage among users of mono- or combined metformin therapy (HR = 0.55, P < .01; HR = 0.63, P < .02). Concomitant use of metformin and statin provided a synergistic OS and DFS benefit (HR = 0.42, P < .01; HR = 0.44, P < .01). Despite significant tobacco and alcohol use history, patients with upper gastrointestinal cancers derived enhanced cancer outcomes from this combination (HR = 0.34, P < .01; HR = 0.43, P < .02), while receiving a statin without metformin or metformin without a statin did not provide significant cancer related benefits. CONCLUSION: Use of statin and metformin provides a synergistic improvement in gastrointestinal malignancies outcomes. PMID- 26811339 TI - PqsBC, a Condensing Enzyme in the Biosynthesis of the Pseudomonas aeruginosa Quinolone Signal: CRYSTAL STRUCTURE, INHIBITION, AND REACTION MECHANISM. AB - Pseudomonas aeruginosaproduces a number of alkylquinolone-type secondary metabolites best known for their antimicrobial effects and involvement in cell cell communication. In the alkylquinolone biosynthetic pathway, the beta-ketoacyl (acyl carrier protein) synthase III (FabH)-like enzyme PqsBC catalyzes the condensation of octanoyl-coenzyme A and 2-aminobenzoylacetate (2-ABA) to form the signal molecule 2-heptyl-4(1H)-quinolone. PqsBC, a potential drug target, is unique for its heterodimeric arrangement and an active site different from that of canonical FabH-like enzymes. Considering the sequence dissimilarity between the subunits, a key question was how the two subunits are organized with respect to the active site. In this study, the PqsBC structure was determined to a 2 A resolution, revealing that PqsB and PqsC have a pseudo-2-fold symmetry that unexpectedly mimics the FabH homodimer. PqsC has an active site composed of Cys 129 and His-269, and the surrounding active site cleft is hydrophobic in character and approximately twice the volume of related FabH enzymes that may be a requirement to accommodate the aromatic substrate 2-ABA. From physiological and kinetic studies, we identified 2-aminoacetophenone as a pathway-inherent competitive inhibitor of PqsBC, whose fluorescence properties could be used forin vitrobinding studies. In a time-resolved setup, we demonstrated that the catalytic histidine is not involved in acyl-enzyme formation, but contributes to an acylation-dependent increase in affinity for the second substrate 2-ABA. Introduction of Asn into the PqsC active site led to significant activity toward the desamino substrate analog benzoylacetate, suggesting that the substrate 2-ABA itself supplies the asparagine-equivalent amino function that assists in catalysis. PMID- 26811341 TI - Taste and Smell Disturbance Resulting From Midodrine. AB - OBJECTIVE: To report a case of dysgeusia and dysosmia following midodrine initiation. METHODS/CASE SUMMARY: A 58-year-old male started midodrine 5 mg tablets 3 times a day for orthostatic hypotension. Two weeks after starting, he began complaining of dysgeusia and dysosmia. He also reported less of an appetite at this time but did not realize it was due to symptoms. He reported his symptoms as tolerable and chose to continue the medicine. At follow-up contact 7 days later, the symptoms were still present but diminishing. MAIN RESULTS/DISCUSSION: Midodrine is used for symptoms of orthostatic hypotension. Dysgeusia and dysosmia are not common adverse events and are not included in the manufacturer's labeling. There is only one other published case report of this reaction. Our patient only admitted to slight appetite suppression, but it may be more profound in some. The reaction may be dose related, but there is not enough information to make this conclusion. PRINCIPAL CONCLUSIONS: Using midodrine may result in dysgeusia and dysosmia. According to this case, both adverse effects may lessen or resolve over time with the use of the medication. PMID- 26811342 TI - Persistent tachypnoea in an infant with cystic lung lucencies on CT scan. PMID- 26811343 TI - Lung function and airway obstruction: associations with circulating markers of cardiac function and incident heart failure in older men-the British Regional Heart Study. AB - AIMS: The association between lung function and cardiac markers and heart failure (HF) has been little studied in the general older population. We have examined the association between lung function and airway obstruction with cardiac markers N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) and risk of incident HF in older men. METHODS AND RESULTS: Prospective study of 3242 men aged 60-79 years without prevalent HF or myocardial infarction followed up for an average period of 13 years, in whom 211 incident HF cases occurred. Incident HF was examined in relation to % predicted FEV1 and FVC. The Global Initiative on Obstructive Lung Diseases spirometry criteria were used to define airway obstruction. Reduced FEV1, but not FVC in the normal range, was significantly associated with increased risk of HF after adjustment for established HF risk factors including inflammation. The adjusted HRs comparing men in the 6-24th percentile with the highest quartile were 1.91 (1.24 to 2.94) and 1.30 (0.86 to 1.96) for FEV1 and FVC, respectively. FEV1 and FVC were inversely associated with NT-proBNP and cTnT, although the association between FEV1 and incident HF remained after adjustment for NT-proBNP and cTnT. Compared with normal subjects (FEV1/FVC >=0.70 and FVC>=80%), moderate or severe (FEV1/FVC <0.70 and FEV1 <80%) airflow obstruction was independently associated with HF ((adjusted relative risk 1.59 (1.08 to 2.33)). Airflow restriction (FEV1/FVC >=0.70 and FVC <80%) was not independently associated with HF. CONCLUSIONS: Reduced FEV1 reflecting airflow obstruction is associated with cardiac dysfunction and increased risk of incident HF in older men. PMID- 26811344 TI - Antioxidant and hepatoprotective effect of polyphenols from apple pomace extract via apoptosis inhibition and Nrf2 activation in mice. AB - Industrial apple pomace, a biowaste generated during apple processing, is rich in cell wall polysaccharides and phenolics. These biologically active compounds are reported to be highly beneficial from the nutritional and health point of view. In the present study, the total phenolic content in the apple pomace aqueous extract (APE) was estimated and evaluated for its possible antioxidant and hepatoprotective efficacy in carbon tetrachloride (CCl4)-induced liver injury mice model. The aqueous extract exhibited 2,2-diphenyl-2-picrylhydrazyl free radical scavenging activity in vitro. Under in vivo study, mice were treated with APE (200 mg and 400 mg/kg body weight) for 2 weeks prior to the administration of CCl4 (30% v/v). The serum liver injury markers alanine transaminase, aspartate transaminase, and alkaline phosphatase were significantly lowered by APE in a dose-dependent manner. The levels of antioxidant parameters superoxide dismutase (SOD), reduced glutathione (redGSH), and lipid peroxidation were also improved by APE in liver homogenate. Histopathological studies revealed that APE treatment significantly lowered the CCl4-induced necrotic changes in the liver. Furthermore, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end-labeling assay showed that CCl4-induced apoptosis in the liver was significantly inhibited by APE in a dose-dependent manner. Immunohistochemistry results showed higher expression of nuclear erythroid 2-related factor 2 (Nrf2) in the liver of the APE-treated mice, a key regulator of antioxidative response. In conclusion, the results of the present study revealed the hepatoprotective efficacy of APE by inhibiting CCl4-induced apoptosis, which is due to its antioxidant activity and the ability to induce Nrf2 protein expression. PMID- 26811345 TI - Endocrine disruption and oxidative stress implications of artemether-lumefantrine combination therapy in the ovary and uterus of rats. AB - In the current study, we evaluated the endocrine disruption effect and oxidative stress implication of therapeutic dose of artemether-lumefantrine combination therapy on the ovary and uterus of rats. In this respect, female rats were divided into four groups: animals were per orally treated with tween 80 (control), artemether (4 mg kg-1 body weight), lumefantrine (24 mg kg-1 body weight) and artemether-lumefantrine (artemether, 4 mg kg-1 body weight and lumefantrine, 24 mg kg-1 body weight). We found that therapeutic doses of the drugs did not change the levels of ovarian hydrogen peroxide (H2O2) and malondialdehyde (MDA), but increased uterine levels of H2O2 and MDA and reduced ovarian and uterine levels of reduced glutathione. In addition, whilst ovarian glutathione peroxidase (GPx) activity reduced in the lumefantrine monotherapy group, uterine GPx increased in the artemether monotherapy as well as the artemether-lumefantrine groups. Furthermore, the drugs reduced ovarian and uterine glutathione- S-transferase and uterine superoxide dismutase activities. The drugs reduced oestrogen level, whereas follicle-stimulating hormone was reduced by lumefantrine and artemether-lumefantrine therapies. Additionally, artemether and lumefantrine monotherapies significantly increased prolactin and progesterone levels compared with the control ( p < 0.05). The results suggest that in the absence of malarial parasite infection, the drugs induced oxidative stress in the ovary and uterus and disrupt hormonal balance in the rats. PMID- 26811346 TI - Merkel cell carcinoma: value of sentinel lymph-node status and adjuvant radiation therapy. AB - BACKGROUND: Sentinel lymph-node (LN) biopsy (SLNB) is a valuable tool to assess the regional LN status in Merkel cell carcinoma (MCC). However, its prognostic value is still debated. This study was undertaken to assess SLNB usefulness for MCC management and to determine the impact of SLNB status on disease-free survival (DFS) and overall survival (OS) by comparing SLNB-positive versus negative patients according to demographic, clinical and treatment characteristics. PATIENTS AND METHODS: In this retrospective, multicenter observational study, SLNB was proposed to all patients referred for clinically N0 MCC. Treatment schedule consisted of wide-margin surgical resection of primary MCC followed by adjuvant radiation therapy (aRT) to the primary site and, for SLNB-positive patients, radical LN dissection followed by regional aRT. Univariate and multivariate analyses determined factors associated with DFS and OS. RESULTS: Among 87 patients with successful SLNB, 21 (24.1%) were SLNB positive. Median follow-up for the entire series was 39 months; respective 3-year DFS and OS rates were 73% and 81.4%, respectively. Univariate analysis (all patients) identified SLNB-negativity as being associated with prolonged OS (P = 0.013) and aRT (all sites considered) was associated with longer DFS (P = 0.004) and OS (P = 0.018). Multivariate analysis (all patients) retained SLNB status and aRT (all sites considered) as being associated with improved DFS (P = 0.014 and 0.0008) and OS (P = 0.0020 and 0.0019). Moreover, for SLNB-negative patients, tumor-bed irradiation was also significantly associated with prolonged DFS (P = 0.006) and OS (P = 0.014). CONCLUSIONS: The present study demonstrates that SLNB negativity is a strong predictor of longer DFS and OS in stage I and II MCC patients. The similar benefit for aRT on tumor bed observed in this study has to be confirmed by a prospective study. The results advocate for SLNB being considered to all MCC patients. PMID- 26811348 TI - Ovarian suppression during chemotherapy increases pregnancy rate in survivors. PMID- 26811347 TI - Transformation of ALK rearrangement-positive adenocarcinoma to small-cell lung cancer in association with acquired resistance to alectinib. PMID- 26811349 TI - Reply to the letter to the editor 'A randomized trial of intensive versus minimal surveillance of patients with resected Dukes B2-C colorectal carcinoma' by Rosati et al. PMID- 26811350 TI - Periodontal disease and risk of all cancers among male never smokers: an updated analysis of the Health Professionals Follow-up Study. AB - BACKGROUND: Periodontal disease has a direct impact on the immune response and has been linked to several chronic diseases, including atherosclerosis and stroke. Few studies have examined the association between periodontal disease and cancer. PATIENTS AND METHODS: A total of 19 933 men reported being never smokers (of cigarette, pipes or cigars) in the Health Professionals' Follow-up Study. Periodontal disease status and teeth number were self-reported at baseline and during follow-up. All cancers were ascertained during 26 years of follow-up. Cox's proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) adjusting for risk factors. RESULTS: A 13% increase in total cancer was observed among men reporting periodontitis at baseline, and a 45% increase in risk was observed among men with advanced periodontitis (periodontitis with <17 remaining teeth). Periodontitis was not associated with prostate cancer, colorectal cancer or melanoma, the three most common cancers in this cohort of never smokers, but a 33% increase in risk was observed for smoking-related cancers (lung, bladder, oropharnygeal, esophageal, kidney, stomach and liver cancers; HR = 1.33, 95% CI 1.07-1.65). Men with advanced periodontitis had an HR of 2.57 (95% CI 1.56-4.21; P = 0.0002) for smoking-related cancers, compared with men who did not have periodontitis and had 17 teeth or more. Advanced periodontitis was associated with elevated risks of esophageal and head and neck cancers (HR = 6.29, 95% CI 2.13-18.6; based on five cases with advanced periodontitis) and bladder cancer (HR = 5.06, 95% CI 2.32 11.0; based on nine cases with advanced periodontitis). CONCLUSIONS: Advanced periodontitis was associated with a 2.5-fold increase in smoking-related cancers among never smokers. Periodontitis may impact cancer risk through system immune dysregulation. Further studies need to examine the immune impact of advanced periodontitis on cancer, especially for cancers known to be caused by smoking. PMID- 26811351 TI - Workload Capacity: A Response Time-Based Measure of Automation Dependence. AB - OBJECTIVE: An experiment used the workload capacity measure C(t) to quantify the processing efficiency of human-automation teams and identify operators' automation usage strategies in a speeded decision task. BACKGROUND: Although response accuracy rates and related measures are often used to measure the influence of an automated decision aid on human performance, aids can also influence response speed. Mean response times (RTs), however, conflate the influence of the human operator and the automated aid on team performance and may mask changes in the operator's performance strategy under aided conditions. The present study used a measure of parallel processing efficiency, or workload capacity, derived from empirical RT distributions as a novel gauge of human automation performance and automation dependence in a speeded task. METHOD: Participants performed a speeded probabilistic decision task with and without the assistance of an automated aid. RT distributions were used to calculate two variants of a workload capacity measure, COR(t) and CAND(t). RESULTS: Capacity measures gave evidence that a diagnosis from the automated aid speeded human participants' responses, and that participants did not moderate their own decision times in anticipation of diagnoses from the aid. CONCLUSION AND APPLICATION: Workload capacity provides a sensitive and informative measure of human-automation performance and operators' automation dependence in speeded tasks. PMID- 26811352 TI - Secondhand hookah smoke: an occupational hazard for hookah bar employees. AB - BACKGROUND: Despite the increasing popularity of hookah bars, there is a lack of research assessing the health effects of hookah smoke among employees. This study investigated indoor air quality in hookah bars and the health effects of secondhand hookah smoke on hookah bar workers. METHODS: Air samples were collected during the work shift of 10 workers in hookah bars in New York City (NYC). Air measurements of fine particulate matter (PM2.5), fine black carbon (BC2.5), carbon monoxide (CO), and nicotine were collected during each work shift. Blood pressure and heart rate, markers of active smoking and secondhand smoke exposure (exhaled CO and saliva cotinine levels), and selected inflammatory cytokines in blood (ineterleukin (IL)-1b, IL-6, IL-8, interferon gamma (IFN gamma), tumour necrosis factor (TNF-alpha)) were assessed in workers immediately prior to and immediately after their work shift. RESULTS: The PM2.5 (gravimetric) and BC2.5 concentrations in indoor air varied greatly among the work shifts with mean levels of 363.8 ug/m3 and 2.2 ug/m3, respectively. The mean CO level was 12.9 ppm with a peak value of 22.5 ppm CO observed in one hookah bar. While heart rate was elevated by 6 bpm after occupational exposure, this change was not statistically significant. Levels of inflammatory cytokines in blood were all increased at postshift compared to preshift testing with IFN-Upsilon increasing from 0.85 (0.13) to 1.6 (0.25) (mean (standard error of the mean; SEM)) pg/mL (p<0.01). Exhaled CO levels were significantly elevated after the work shift with 2 of 10 workers having values >90 ppm exhaled CO. CONCLUSIONS: These results demonstrate that hookah bars have elevated concentrations of indoor air pollutants that appear to cause adverse health effects in employees. These data indicate the need for further research and a marked need for better air quality monitoring and policies in such establishments to improve the indoor air quality for workers and patrons. PMID- 26811353 TI - Longitudinal study of e-cigarette use and onset of cigarette smoking among high school students in Hawaii. AB - OBJECTIVE: Use of electronic cigarettes (e-cigarettes) is prevalent among adolescents, but there is little knowledge about the consequences of their use. We examined, longitudinally, how e-cigarette use among adolescents is related to subsequent smoking behaviour. METHODS: Longitudinal school-based survey with a baseline sample of 2338 students (9th and 10th graders, mean age 14.7 years) in Hawaii surveyed in 2013 (time 1, T1) and followed up 1 year later (time 2, T2). We assessed e-cigarette use, tobacco cigarette use, and psychosocial covariates (demographics, parental support and monitoring, and sensation seeking and rebelliousness). Regression analyses including the covariates tested whether e cigarette use was related to the onset of smoking among youth who had never smoked cigarettes, and to change in smoking frequency among youth who had previously smoked cigarettes. RESULTS: Among T1 never-smokers, those who had used e-cigarettes at T1 were more likely to have smoked cigarettes at T2; for a complete-case analysis, adjusted OR=2.87, 95% CI 2.03 to 4.05, p<0.0001. Among ever-smokers at T1, using e-cigarettes was not related to significant change in their frequency of smoking at T2. Uptake of e-cigarette use among T1 never-users of either product was predicted by age, Caucasian or Native Hawaiian (vs Asian American) ethnicity, lower parental education and parental support, higher rebelliousness, and perception of e-cigarettes as healthier. CONCLUSIONS: Adolescents who use e-cigarettes are more likely to start smoking cigarettes. This result together with other findings suggests that policies restricting adolescents' access to e-cigarettes may have a rationale from a public health standpoint. PMID- 26811354 TI - A Quantitative Proteomic Analysis of In Vitro Assembled Chromatin. AB - The structure of chromatin is critical for many aspects of cellular physiology and is considered to be the primary medium to store epigenetic information. It is defined by the histone molecules that constitute the nucleosome, the positioning of the nucleosomes along the DNA and the non-histone proteins that associate with it. These factors help to establish and maintain a largely DNA sequence independent but surprisingly stable structure. Chromatin is extensively disassembled and reassembled during DNA replication, repair, recombination or transcription in order to allow the necessary factors to gain access to their substrate. Despite such constant interference with chromatin structure, the epigenetic information is generally well maintained. Surprisingly, the mechanisms that coordinate chromatin assembly and ensure proper assembly are not particularly well understood. Here, we use label free quantitative mass spectrometry to describe the kinetics of in vitro assembled chromatin supported by an embryo extract prepared from preblastoderm Drosophila melanogaster embryos. The use of a data independent acquisition method for proteome wide quantitation allows a time resolved comparison of in vitro chromatin assembly. A comparison of our in vitro data with proteomic studies of replicative chromatin assembly in vivo reveals an extensive overlap showing that the in vitro system can be used for investigating the kinetics of chromatin assembly in a proteome-wide manner. PMID- 26811355 TI - Changes in the Plasma Proteome of Manduca sexta Larvae in Relation to the Transcriptome Variations after an Immune Challenge: Evidence for High Molecular Weight Immune Complex Formation. AB - Manduca sextais a lepidopteran model widely used to study insect physiological processes, including innate immunity. In this study, we explored the proteomes of cell-free hemolymph from larvae injected with a sterile buffer (C for control) or a mixture of bacteria (I for induced). Of the 654 proteins identified, 70 showed 1.67 to >200-fold abundance increases after the immune challenge; 51 decreased to 0-60% of the control levels. While there was no strong parallel between plasma protein levels and their transcript levels in hemocytes or fat body, the mRNA level changes (i.e.I/C ratios of normalized read numbers) in the tissues concurred with their protein level changes (i.e.I/C ratios of normalized spectral counts) with correlation coefficients of 0.44 and 0.57, respectively. Better correlations support that fat body contributes a more significant portion of the plasma proteins involved in various aspects of innate immunity. Consistently, ratios of mRNA and protein levels were better correlated for immunity-related proteins than unrelated ones. There is a set of proteins whose apparent molecular masses differ considerably from the calculatedMr's, suggestive of posttranslational modifications. In addition, some lowMrproteins were detected in the range of 80 to >300 kDa on a reducing SDS-polyacrylamide gel, indicating the existence of highMrcovalent complexes. We identified 30 serine proteases and their homologs, 11 of which are known members of an extracellular immune signaling network. Along with our quantitative transcriptome data, the protein identification, inducibility, and association provide leads toward a focused exploration of humoral immunity inM. sexta. PMID- 26811356 TI - Rapid Oligo-Galacturonide Induced Changes in Protein Phosphorylation in Arabidopsis. AB - The wall-associated kinases (WAKs)(1)are receptor protein kinases that bind to long polymers of cross-linked pectin in the cell wall. These plasma-membrane associated protein kinases also bind soluble pectin fragments called oligo galacturonides (OGs) released from the wall after pathogen attack and damage. WAKs are required for cell expansion during development but bind water soluble OGs generated from walls with a higher affinity than the wall-associated polysaccharides. OGs activate a WAK-dependent, distinct stress-like response pathway to help plants resist pathogen attack. In this report, a quantitative mass-spectrometric-based phosphoproteomic analysis was used to identify Arabidopsis cellular events rapidly induced by OGsin planta Using N(14/)N(15)isotopicin vivometabolic labeling, we screened 1,000 phosphoproteins for rapid OG-induced changes and found 50 proteins with increased phosphorylation, while there were none that decreased significantly. Seven of the phosphosites within these proteins overlap with those altered by another signaling molecule plants use to indicate the presence of pathogens (the bacterial "elicitor" peptide Flg22), indicating distinct but overlapping pathways activated by these two types of chemicals. Genetic analysis of genes encoding 10 OG-specific and two Flg22/OG-induced phosphoproteins reveals that null mutations in eight proteins compromise the OG response. These phosphorylated proteins with genetic evidence supporting their role in the OG response include two cytoplasmic kinases, two membrane-associated scaffold proteins, a phospholipase C, a CDPK, an unknown cadmium response protein, and a motor protein. Null mutants in two proteins, the putative scaffold protein REM1.3, and a cytoplasmic receptor like kinase ROG2, enhance and suppress, respectively, a dominantWAKallele. Altogether, the results of these chemical and genetic experiments reveal the identity of several phosphorylated proteins involved in the kinase/phosphatase-mediated signaling pathway initiated by cell wall changes. PMID- 26811358 TI - Medical isotope supply raises concerns. PMID- 26811357 TI - Proteomic Analysis of Rhizoctonia solani Identifies Infection-specific, Redox Associated Proteins and Insight into Adaptation to Different Plant Hosts. AB - Rhizoctonia solaniis an important root infecting pathogen of a range of food staples worldwide including wheat, rice, maize, soybean, potato and others. Conventional resistance breeding strategies are hindered by the absence of tractable genetic resistance in any crop host. Understanding the biology and pathogenicity mechanisms of this fungus is important for addressing these disease issues, however, little is known about howR. solanicauses disease. This study capitalizes on recent genomic studies by applying mass spectrometry based proteomics to identify soluble, membrane-bound and culture filtrate proteins produced under wheat infection and vegetative growth conditions. Many of the proteins found in the culture filtrate had predicted functions relating to modification of the plant cell wall, a major activity required for pathogenesis on the plant host, including a number found only under infection conditions. Other infection related proteins included a high proportion of proteins with redox associated functions and many novel proteins without functional classification. The majority of infection only proteins tested were confirmed to show transcript up-regulation during infection including a thaumatin which increased susceptibility toR. solaniwhen expressed inNicotiana benthamiana In addition, analysis of expression during infection of different plant hosts highlighted how the infection strategy of this broad host range pathogen can be adapted to the particular host being encountered. Data are available via ProteomeXchange with identifier PXD002806. PMID- 26811359 TI - Will new isotope sources be ready in time? PMID- 26811360 TI - Pushback on drug ads. PMID- 26811361 TI - Risk of hypoglycemia following intensification of metformin treatment with insulin versus sulfonylurea. AB - BACKGROUND: Hypoglycemia remains a common life-threatening event associated with diabetes treatment. We compared the risk of first or recurrent hypoglycemia event among metformin initiators who intensified treatment with insulin versus sulfonylurea. METHODS: We assembled a retrospective cohort using databases of the Veterans Health Administration, Medicare and the National Death Index. Metformin initiators who intensified treatment with insulin or sulfonylurea were followed to either their first or recurrent hypoglycemia event using Cox proportional hazard models. Hypoglycemia was defined as hospital admission or an emergency department visit for hypoglycemia, or an outpatient blood glucose value of less than 3.3 mmol/L. We conducted additional analyses for risk of first hypoglycemia event, with death as the competing risk. RESULTS: Among 178,341 metformin initiators, 2948 added insulin and 39,990 added sulfonylurea. Propensity score matching yielded 2436 patients taking metformin plus insulin and 12,180 taking metformin plus sulfonylurea. Patients took metformin for a median of 14 (interquartile range [IQR] 5-30) months, and the median glycated hemoglobin level was 8.1% (IQR 7.2%-9.9%) at intensification. In the group who added insulin, 121 first hypoglycemia events occurred, and 466 first events occurred in the group who added sulfonylurea (30.9 v. 24.6 events per 1000 person-years; adjusted hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.06-1.59). For recurrent hypoglycemia, there were 159 events in the insulin group and 585 events in the sulfonylurea group (39.1 v. 30.0 per 1000 person-years; adjusted HR 1.39, 95% CI 1.12-1.72). In separate competing risk analyses, the adjusted HR for hypoglycemia was 1.28 (95% CI 1.04-1.56). INTERPRETATION: Among patients using metformin who could use either insulin or sulfonylurea, the addition of insulin was associated with a higher risk of hypoglycemia than the addition of sulfonylurea. This finding should be considered by patients and clinicians when discussing the risks and benefits of adding insulin versus a sulfonylurea. PMID- 26811362 TI - Bleeding associated with coadministration of rivaroxaban and clarithromycin. PMID- 26811363 TI - Fetal alcohol spectrum disorder: reconsidering blame. PMID- 26811364 TI - What Does Self-rated Health Mean? Changes and Variations in the Association of Obesity with Objective and Subjective Components Of Self-rated Health. AB - There are concerns about the meaning of self-rated health (SRH) and the factors individuals consider. To illustrate how SRH is contextualized, we examine how the obesity-SRH association varies across age, periods, and cohorts. We decompose SRH into subjective and objective components and use a mechanism-based age-period cohort model approach with four decades (1970s to 2000s) and five birth cohorts of National Health and Nutrition Examination Survey data (N = 26,184). Obese adults rate their health more negatively than non-obese when using overall SRH with little variation by age, period, or cohort. However, when we decomposed SRH into objective and subjective components, the obesity gap widened with increasing age in objective SRH but narrowed in subjective SRH. Additionally, the gap narrowed for more recently born cohorts for objective SRH but widened for subjective SRH. The results provide indirect evidence that the relationship between obesity and SRH is socially patterned according to exposure to information about obesity and the availability of resources to manage it. PMID- 26811366 TI - North Carolina law expands pool of eligible healthcare professionals to oversee executions by lethal injection. PMID- 26811365 TI - Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees. AB - A novel Protocol Ethics Tool Kit ('Ethics Tool Kit') has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval. PMID- 26811367 TI - Recovery position significantly associated with a reduced admission rate of children with loss of consciousness. AB - BACKGROUND: Loss of consciousness (LOC) is often seen in children. The response of caregivers to a child with LOC has been poorly investigated. Potential caregivers (parents, teachers) seem to have a poor knowledge of the recovery position (RP)-that is, the position into which an unconscious child should be placed in order to protect the airway. OBJECTIVES: To report the management and diagnoses of LOC in childhood, and to evaluate variables associated with an increased hospital admission rate. METHODS: We conducted a prospective cohort study of consecutive children aged between 0 and 18 years diagnosed with LOC at 11 paediatric emergency departments (PEDs) of 6 European countries. The enrolment period was 3 months. Data were obtained from parental interviews, PED reports and clinical examination. RESULTS: 553 children were enrolled. The most frequent final diagnoses causing LOC were seizures (n=278, 50.3%), and vasovagal syncope (n=124, 22.4%). Caregivers put the child in the RP in 145 cases (26.2%). The RP was independently associated with a significant decrease in the admission rate (aOR=0.28; 95% CI 0.17 to 0.48; p<0.0001). CONCLUSIONS: Our study demonstrates for the first time that the RP may reduce the admission rate of infants with LOC. Caregivers often perform inadequate manoeuvres when a child becomes unconscious. Campaigns aiming at increasing knowledge of the RP should be promoted. PMID- 26811368 TI - Overall and cause-specific mortality in systemic lupus erythematosus: an updated meta-analysis. AB - AIMS: This study aimed to assess all-cause and cause-specific standardized mortality ratios (SMRs) in patients with systemic lupus erythematosus (SLE). METHODS: We surveyed studies examining all-cause and/or cause-specific SMR in patients with SLE compared to the general population using PUBMED, EMBASE and Cochrane databases and manual searches. We performed a meta-analysis of all cause, sex-specific, ethnicity-specific, and cause-specific SMRs in SLE patients. RESULTS: Fifteen reports including 26,101 patients with SLE with 4640 deaths met the inclusion criteria. Compared to the general population, all-cause SMR was significantly increased 2.6-fold in patients with SLE (SMR 2.663, 95% CI 2.090 3.393, p < 1.0 * 10(-8)). Stratification by ethnicity showed that all-cause SMR was 2.721 (95% CI 1.867-3.966, p = 1.9 * 10(-6)) in Caucasians and 2.587 (95% CI 1.475-4.535, p = 0.001) in Asians. Sex-specific meta-analysis revealed that all cause SMR was 3.141 (95% CI 2.351-4.198, p < 1.0 * 10(-8)) for women and 3.516 (95% CI 2.928-4.221, p < 1.0 * 10(-8)) for men. The risk of mortality was significantly increased for mortality due to renal disease (SMR 4.689, 95% CI 2.357-9.330, p = 1.10 * 10(-5)), cardiovascular disease (CVD) (SMR 2.253, 95% CI 1.304-3.892, p = 0.004), and infection (SMR 4.980, 95% CI 3.876-6.398, p < 1.0 * 10(-8)), although there was no significant increase in SMR for mortality due to cancer (SMR 1.163, 95% CI 0.572-2.363, p = 0.676). CONCLUSIONS: Patients with SLE had higher rates of death from all causes, regardless of sex, ethnicity, renal disease, CVD or infection. However, the risk of death due to malignancy was not increased. PMID- 26811369 TI - Coexistence of systemic lupus erythematosus and familial Mediterranean fever in a pediatric patient. PMID- 26811370 TI - Pregnancies in women with systemic lupus erythematosus and antiphospholipid antibodies. AB - Systemic lupus erythematosus (SLE) has preponderance in women in their childbearing years; consequently pregnancy has always been an important issue of concern for the patient and the treating physician. Based upon numerous reports on successful pregnancy outcomes in the past decades, the initial advice against pregnancy in the 1950s has been replaced by a common understanding that women with SLE often have successful pregnancy outcomes, and clinicians therefore advise on pregnancy planning, including possible drug adjustments, timing and close surveillance. The recently published Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus (PROMISSE) study, so far the largest multicentre cohort study of pregnant women with underlying stable SLE, has given some important answers to long-discussed questions. Future studies on data collected from the PROMISSE cohort will hopefully identify serological biomarkers, possibly genes, and in addition, give valuable information about underlying disease mechanisms. PMID- 26811371 TI - Aortic aneurysm association with SLE - a case-control study. AB - OBJECTIVES: Aortic aneurysm is a life threatening cardiovascular complication in patients with systemic lupus erythematosus (SLE).The purpose of this study was to investigate the association between SLE and occurrence of aortic aneurysms. METHODS: Patients with SLE were compared with age- and sex-matched controls regarding the proportion of aortic aneurysm in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. RESULTS: The study included 5018 patients with SLE and 25,090 age- and sex-matched controls. The proportion of aortic aneurysm in patients with SLE was increased compared with the proportion in controls (0.6% and 0.1%, respectively, p < 0.001). In a multivariate analysis SLE was associated with the coexistence of aortic aneurysms (odds ratio 2.06, 95% confidence interval 1.21-3.51). CONCLUSIONS: Patients with SLE have a higher proportion of aortic aneurysms as compared with matched controls. Therefore, physicians treating patients with SLE should be aware of this life threatening association. PMID- 26811372 TI - Eppur Si Muove: vitamin D is essential in preventing and modulating SLE. AB - Systemic lupus erythematosus (abbreviated SLE or lupus) is a systemic autoimmune disease, with genetic, immunologic, hormonal, and environmental factors.(1)One of the environmental factors that has been studied over the years is vitamin D, which is created in the human body in response to exposure to sunlight and ultraviolet (UV) radiation.This review aims at examining findings from recent years, specifically 2013-2014, regarding the relationship between vitamin D deficiency and SLE flares, severity, and clinical manifestation, as well as to examine the treatment options derived from this relationship. PMID- 26811373 TI - Is single room hospital accommodation associated with differences in healthcare associated infection, falls, pressure ulcers or medication errors? A natural experiment with non-equivalent controls. AB - OBJECTIVES: A wide range of patient benefits have been attributed to single room hospital accommodation including a reduction in adverse patient safety events. However, studies have been limited to the US with limited evidence from elsewhere. The aim of this study was to assess the impact on safety outcomes of the move to a newly built all single room acute hospital. METHODS: A natural experiment investigating the move to 100% single room accommodation in acute assessment, surgical and older people's wards. Move to 100% single room accommodation compared to 'steady state' and 'new build' control hospitals. Falls, pressure ulcer, medication error, meticillin-resistant Staphylococcus aureus and Clostridium difficile rates from routine data sources were measured over 36 months. RESULTS: Five of 15 time series in the wards that moved to single room accommodation revealed changes that coincided with the move to the new all single room hospital: specifically, increased fall, pressure ulcer and Clostridium difficile rates in the older people's ward, and temporary increases in falls and medication errors in the acute assessment unit. However, because the case mix of the older people's ward changed, and because the increase in falls and medication errors on the acute assessment ward did not last longer than six months, no clear effect of single rooms on the safety outcomes was demonstrated. There were no changes to safety events coinciding with the move at the new build control site. CONCLUSION: For all changes in patient safety events that coincided with the move to single rooms, we found plausible alternative explanations such as case-mix change or disruption as a result of the re-organization of services after the move. The results provide no evidence of either benefit or harm from all single room accommodation in terms of safety-related outcomes, although there may be short-term risks associated with a move to single rooms. PMID- 26811374 TI - How is feedback from national clinical audits used? Views from English National Health Service trust audit leads. AB - OBJECTIVE: To explore how the output of national clinical audits in England is used by professionals and whether and how their impact could be enhanced. METHODS: A mixed-methods study with the primary recipients of four national clinical audits of cancer care of 607 local audit leads, 274 (45%) completed a questionnaire and 32 participated in an interview. Our questions focused on how the audits were used and whether barriers existed to using the audits for local service improvement. We described variation in questionnaire responses between the audits using chi-squared tests. Results are reported as percentages with their 95% confidence intervals. Qualitative data were analysed using Framework analysis. RESULTS: More than 90% of survey respondents believed that the audit findings were relevant to their clinical work, and interviewees described how they used the audits for a range of purposes. Forty-two percent of survey respondents said they had changed their clinical practice, and 56% had implemented service improvements in response to the audits. The degree of change differed between the four audits, evident in both the questionnaire and the interview data. In the interviews, two recurring barriers emerged: (1) the importance of data quality, which, in turn, influenced the perceived relevance and validity of the audit data and therefore the ability to make changes based on it and (2) the need for clear presentation of benchmarked local performance data. The perceived authority and credibility of the professional bodies supporting the audits was a key factor underpinning the use of the audit findings. CONCLUSION: National cancer audit and feedback is used to improve services, but their impact could be enhanced by improving the data quality and relevance of feedback. PMID- 26811375 TI - Lessons for major system change: centralization of stroke services in two metropolitan areas of England. AB - OBJECTIVES: Our aim was to identify the factors influencing the selection of a model of acute stroke service centralization to create fewer high-volume specialist units in two metropolitan areas of England (London and Greater Manchester). It considers the reasons why services were more fully centralized in London than in Greater Manchester. METHODS: In both areas, we analysed 316 documents and conducted 45 interviews with people leading transformation, service user organizations, providers and commissioners. Inductive and deductive analyses were used to compare the processes underpinning change in each area, with reference to propositions for achieving major system change taken from a realist review of the existing literature (the Best framework), which we critique and develop further. RESULTS: In London, system leadership was used to overcome resistance to centralization and align stakeholders to implement a centralized service model. In Greater Manchester, programme leaders relied on achieving change by consensus and, lacking decision-making authority over providers, accommodated rather than challenged resistance by implementing a less radical transformation of services. CONCLUSIONS: A combination of system (top-down) and distributed (bottom-up) leadership is important in enabling change. System leadership provides the political authority required to coordinate stakeholders and to capitalize on clinical leadership by aligning it with transformation goals. Policy makers should examine how the structures of system authority, with performance management and financial levers, can be employed to coordinate transformation by aligning the disparate interests of providers and commissioners. PMID- 26811376 TI - Knowledge, Attitude, and Practice in the Management of Mixed Arteriovenous Leg Ulcers. AB - Leg ulceration is a chronic health condition that constitutes a significant disease burden. In this cross-sectional descriptive study, a sample of wound care clinicians were asked to respond to a web-based survey. Based on a review of literature and recommended best practices in the management of mixed arteriovenous (AV) ulcers, a questionnaire was developed to examine the knowledge, attitude, and practice pattern in the management of AV ulcers. A total of 436 clinicians participated in the survey. A number of assessment techniques were perceived to be relevant for the assessment of AV ulcers; medical history and the appearance of ulcers were the most commonly used methods in clinical practice. While over 80% of the participants conceded that compression should be used to promote wound healing, half of them would consider using compression for AV ulcers if ankle brachial index was less than 0.8. Half of the participants considered an ankle brachial index of 0.8 or higher as the optimal cutoff value for safe compression. The majority of respondents disagreed with the perception that caring for people with AV ulcers was unrewarding. However, challenges to promote treatment adherence, address psychosocial concerns, and optimize symptom management are common. PMID- 26811377 TI - Disruption of somitogenesis by a novel dominant allele of Lfng suggests important roles for protein processing and secretion. AB - Vertebrate somitogenesis is regulated by a segmentation clock. Clock-linked genes exhibit cyclic expression, with a periodicity matching the rate of somite production. In mice, lunatic fringe (Lfng) expression oscillates, and LFNG protein contributes to periodic repression of Notch signaling. We hypothesized that rapid LFNG turnover could be regulated by protein processing and secretion. Here, we describe a novel Lfng allele (Lfng(RLFNG)), replacing the N-terminal sequences of LFNG, which allow for protein processing and secretion, with the N terminus of radical fringe (a Golgi-resident protein). This allele is predicted to prevent protein secretion without altering the activity of LFNG, thus increasing the intracellular half-life of the protein. This allele causes dominant skeletal and somite abnormalities that are distinct from those seen in Lfng loss-of-function embryos. Expression of clock-linked genes is perturbed and mature Hes7 transcripts are stabilized in the presomitic mesoderm of mutant mice, suggesting that both transcriptional and post-transcriptional regulation of clock components are perturbed by RLFNG expression. Contrasting phenotypes in the segmentation clock and somite patterning of mutant mice suggest that LFNG protein may have context-dependent effects on Notch activity. PMID- 26811378 TI - Tpbpa-Cre-mediated deletion of TFAP2C leads to deregulation of Cdkn1a, Akt1 and the ERK pathway, causing placental growth arrest. AB - Loss of TFAP2C in mouse leads to developmental defects in the extra-embryonic compartment with lethality at embryonic day (E)7.5. To investigate the requirement of TFAP2C in later placental development, deletion of TFAP2C was induced throughout extra-embryonic ectoderm at E6.5, leading to severe placental abnormalities caused by reduced trophoblast population and resulting in embryonic retardation by E8.5. Deletion of TFAP2C in TPBPA(+) progenitors at E8.5 results in growth arrest of the junctional zone. TFAP2C regulates its target genes Cdkn1a (previously p21) and Dusp6, which are involved in repression of MAPK signaling. Loss of TFAP2C reduces activation of ERK1/2 in the placenta. Downregulation of Akt1 and reduced activation of phosphorylated AKT in the mutant placenta are accompanied by impaired glycogen synthesis. Loss of TFAP2C led to upregulation of imprinted gene H19 and downregulation of Slc38a4 and Ascl2. The placental insufficiency post E16.5 causes fetal growth restriction, with 19% lighter mutant pups. Knockdown of TFAP2C in human trophoblast choriocarcinoma JAr cells inhibited MAPK and AKT signaling. Thus, we present a model where TFAP2C in trophoblasts controls proliferation by repressing Cdkn1a and activating the MAPK pathway, further supporting differentiation of glycogen cells by activating the AKT pathway. PMID- 26811379 TI - Modulation of junction tension by tumor suppressors and proto-oncogenes regulates cell-cell contacts. AB - Tumor suppressors and proto-oncogenes play crucial roles in tissue proliferation. Furthermore, de-regulation of their functions is deleterious to tissue architecture and can result in the sorting of somatic rounded clones minimizing their contact with surrounding wild-type (wt) cells. Defects in the shape of somatic clones correlate with defects in proliferation, cell affinity, cell-cell adhesion, oriented cell division and cortical contractility. Combining genetics, live-imaging, laser ablation and computer simulations, we aim to analyze whether distinct or similar mechanisms can account for the common role of tumor suppressors and proto-oncogenes in cell-cell contact regulation. In Drosophila epithelia, the tumor suppressors Fat (Ft) and Dachsous (Ds) regulate cell proliferation, tissue morphogenesis, planar cell polarity and junction tension. By analyzing the evolution over time of ft mutant cells and clones, we show that ft clones reduce their cell-cell contacts with the surrounding wt tissue in the absence of concomitant cell divisions and over-proliferation. This contact reduction depends on opposed changes of junction tensions in the clone bulk and its boundary with neighboring wt tissue. More generally, either clone bulk or boundary junction tension is modulated by the activation of Yorkie, Myc and Ras, yielding similar contact reductions with wt cells. Together, our data highlight mechanical roles for proto-oncogene and tumor suppressor pathways in cell-cell interactions. PMID- 26811381 TI - A gradient of maternal Bicaudal-C controls vertebrate embryogenesis via translational repression of mRNAs encoding cell fate regulators. AB - Vertebrate Bicaudal-C (Bicc1) has important biological roles in the formation and homeostasis of multiple organs, but direct experiments to address the role of maternal Bicc1 in early vertebrate embryogenesis have not been reported. Here, we use antisense phosphorothioate-modified oligonucleotides and the host-transfer technique to eliminate specifically maternal stores of both bicc1 mRNA and Bicc1 protein from Xenopus laevis eggs. Fertilization of these Bicc1-depleted eggs produced embryos with an excess of dorsal-anterior structures and overexpressed organizer-specific genes, indicating that maternal Bicc1 is crucial for normal embryonic patterning of the vertebrate embryo. Bicc1 is an RNA-binding protein with robust translational repression function. Here, we show that the maternal mRNA encoding the cell-fate regulatory protein Wnt11b is a direct target of Bicc1 mediated repression. It is well established that the Wnt signaling pathway is crucial to vertebrate embryogenesis. Thus, the work presented here links the molecular function of Bicc1 in mRNA target-specific translation repression to its biological role in the maternally controlled stages of vertebrate embryogenesis. PMID- 26811380 TI - Makorin ortholog LEP-2 regulates LIN-28 stability to promote the juvenile-to adult transition in Caenorhabditis elegans. AB - The heterochronic genes lin-28, let-7 and lin-41 regulate fundamental developmental transitions in animals, such as stemness versus differentiation and juvenile versus adult states. We identify a new heterochronic gene, lep-2, in Caenorhabditis elegans. Mutations in lep-2 cause a delay in the juvenile-to-adult transition, with adult males retaining pointed, juvenile tail tips, and displaying defective sexual behaviors. In both sexes, lep-2 mutants fail to cease molting or produce an adult cuticle. We find that LEP-2 post-translationally regulates LIN-28 by promoting LIN-28 protein degradation. lep-2 encodes the sole C. elegans ortholog of the Makorin (Mkrn) family of proteins. Like lin-28 and other heterochronic pathway members, vertebrate Mkrns are involved in developmental switches, including the timing of pubertal onset in humans. Based on shared roles, conservation and the interaction between lep-2 and lin-28 shown here, we propose that Mkrns, together with other heterochronic genes, constitute an evolutionarily ancient conserved module regulating switches in development. PMID- 26811382 TI - BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors. AB - The pseudostratified epithelium of the lung contains ciliated and secretory luminal cells and basal stem/progenitor cells. To identify signals controlling basal cell behavior we screened factors that alter their self-renewal and differentiation in a clonal organoid (tracheosphere) assay. This revealed that inhibitors of the canonical BMP signaling pathway promote proliferation but do not affect lineage choice, whereas exogenous Bmp4 inhibits proliferation and differentiation. We therefore followed changes in BMP pathway components in vivo in the mouse trachea during epithelial regeneration from basal cells after injury. The findings suggest that BMP signaling normally constrains proliferation at steady state and this brake is released transiently during repair by the upregulation of endogenous BMP antagonists. Early in repair, the packing of epithelial cells along the basal lamina increases, but density is later restored by active extrusion of apoptotic cells. Systemic administration of the BMP antagonist LDN-193189 during repair initially increases epithelial cell number but, following the shedding phase, normal density is restored. Taken together, these results reveal crucial roles for both BMP signaling and cell shedding in homeostasis of the respiratory epithelium. PMID- 26811383 TI - MEF2C regulates outflow tract alignment and transcriptional control of Tdgf1. AB - Congenital heart defects are the most common birth defects in humans, and those that affect the proper alignment of the outflow tracts and septation of the ventricles are a highly significant cause of morbidity and mortality in infants. A late differentiating population of cardiac progenitors, referred to as the anterior second heart field (AHF), gives rise to the outflow tract and the majority of the right ventricle and provides an embryological context for understanding cardiac outflow tract alignment and membranous ventricular septal defects. However, the transcriptional pathways controlling AHF development and their roles in congenital heart defects remain incompletely elucidated. Here, we inactivated the gene encoding the transcription factor MEF2C in the AHF in mice. Loss of Mef2c function in the AHF results in a spectrum of outflow tract alignment defects ranging from overriding aorta to double-outlet right ventricle and dextro-transposition of the great arteries. We identify Tdgf1, which encodes a Nodal co-receptor (also known as Cripto), as a direct transcriptional target of MEF2C in the outflow tract via an AHF-restricted Tdgf1 enhancer. Importantly, both the MEF2C and TDGF1 genes are associated with congenital heart defects in humans. Thus, these studies establish a direct transcriptional pathway between the core cardiac transcription factor MEF2C and the human congenital heart disease gene TDGF1. Moreover, we found a range of outflow tract alignment defects resulting from a single genetic lesion, supporting the idea that AHF-derived outflow tract alignment defects may constitute an embryological spectrum rather than distinct anomalies. PMID- 26811384 TI - The H3K4me3/2 histone demethylase RBR-2 controls axon guidance by repressing the actin-remodeling gene wsp-1. AB - The dynamic regulation of histone modifications is important for modulating transcriptional programs during development. Aberrant H3K4 methylation is associated with neurological disorders, but how the levels and the recognition of this modification affect specific neuronal processes is unclear. Here, we show that RBR-2, the sole homolog of the KDM5 family of H3K4me3/2 demethylases in Caenorhabditis elegans, ensures correct axon guidance by controlling the expression of the actin regulator wsp-1. Loss of rbr-2 results in increased levels of H3K4me3 at the transcriptional start site of wsp-1, with concomitant higher wsp-1 expression responsible for defective axon guidance. In agreement, overexpression of WSP-1 mimics rbr-2 loss, and its depletion restores normal axon guidance in rbr-2 mutants. NURF-1, an H3K4me3-binding protein and member of the chromatin-remodeling complex NURF, is required for promoting aberrant wsp-1 transcription in rbr-2 mutants and its ablation restores wild-type expression of wsp-1 and axon guidance. Thus, our results establish a precise role for epigenetic regulation in neuronal development by demonstrating a functional link between RBR-2 activity, H3K4me3 levels, the NURF complex and the expression of WSP-1. PMID- 26811385 TI - Chinmo is sufficient to induce male fate in somatic cells of the adult Drosophila ovary. AB - Sexual identity is continuously maintained in specific differentiated cell types long after sex determination occurs during development. In the adult Drosophila testis, the putative transcription factor Chronologically inappropriate morphogenesis (Chinmo) acts with the canonical male sex determinant DoublesexM (Dsx(M)) to maintain the male identity of somatic cyst stem cells and their progeny. Here we find that ectopic expression of chinmo is sufficient to induce a male identity in adult ovarian somatic cells, but it acts through a Dsx(M) independent mechanism. Conversely, the feminization of the testis somatic stem cell lineage caused by loss of chinmo is enhanced by expression of the canonical female sex determinant Dsx(F), indicating that chinmo acts in parallel with the canonical sex determination pathway to maintain the male identity of testis somatic cells. Consistent with this finding, ectopic expression of female sex determinants in the adult testis disrupts tissue morphology. The miRNA let-7 downregulates chinmo in many contexts, and ectopic expression of let-7 in the adult testis is sufficient to recapitulate the chinmo loss-of-function phenotype, but we find no apparent phenotypes upon removal of let-7 in the adult ovary or testis. Our finding that chinmo is necessary and sufficient to promote a male identity in adult gonadal somatic cells suggests that the sexual identity of somatic cells can be reprogrammed in the adult Drosophila ovary as well as in the testis. PMID- 26811387 TI - Psychotic disorders cause the greatest mortality disparity among mental disorders, though more deaths are attributable overall to mood and anxiety disorders. PMID- 26811386 TI - The Lhx9-integrin pathway is essential for positioning of the proepicardial organ. AB - The development of the vertebrate embryonic heart occurs by hyperplastic growth as well as the incorporation of cells from tissues outside of the initial heart field. Amongst these tissues is the epicardium, a cell structure that develops from the precursor proepicardial organ on the right side of the septum transversum caudal to the developing heart. During embryogenesis, cells of the proepicardial organ migrate, adhere and envelop the maturing heart, forming the epicardium. The cells of the epicardium then delaminate and incorporate into the heart giving rise to cardiac derivatives, including smooth muscle cells and cardiac fibroblasts. Here, we demonstrate that the LIM homeodomain protein Lhx9 is transiently expressed in Xenopus proepicardial cells and is essential for the position of the proepicardial organ on the septum transversum. Utilizing a small molecule screen, we found that Lhx9 acts upstream of integrin-paxillin signaling and consistently demonstrate that either loss of Lhx9 or disruption of the integrin-paxillin pathway results in mis-positioning of the proepicardial organ and aberrant deposition of extracellular matrix proteins. This leads to a failure of proepicardial cell migration and adhesion to the heart, and eventual death of the embryo. Collectively, these studies establish a requirement for the Lhx9 integrin-paxillin pathway in proepicardial organ positioning and epicardial formation. PMID- 26811388 TI - Diagnostic Accuracy of Renal Mass Biopsy: An Ex Vivo Study of 100 Nephrectomy Specimens. AB - We investigated the diagnostic accuracy of renal mass biopsy in an ex vivo model, as well as compared the agreement of the preoperative radiological diagnosis with the final pathologic diagnosis. Two 18-gauge needle-core and 2 vacuum-needle biopsies were performed ex vivo from the tumors of 100 consecutive patients undergoing radical nephrectomy between 2006 and 2010. The median tumor size was 5.5 cm. There was no significant difference with regard to cylinder length or tissue quality between the sampling methods. At least 1 of 4 needle cores contained diagnostic tissue in 88% of patients. Biopsy specimens identified clear cell (54%), papillary (13%), or chromophobe (5%) renal cell carcinoma; urothelial carcinoma (6%); oncocytoma (5%); liposarcoma (1%); metastatic colorectal carcinoma (1%); squamous cell carcinoma (1%); unclassified renal cell neoplasm (1%); and no tumor sampled (12%). The sensitivity of the biopsy for accurately determining the diagnosis was 88% (95% CI: 79% to 93%). The specificity was 100% (95% CI: 17% to 100%). Biopsy grade correlated strongly with final pathology (83.5% agreement). There was no difference in average tumor size in cases with the same versus higher grade on final pathology (5.87 vs 5.97; P = .87). Appraisal of tumor histology by radiology agreed with the pathologic diagnosis in 68% of cases. Provided that the biopsy samples the tumor tissue in a renal mass, pathologic analysis is of great diagnostic value in respect of grade and tumor type and correlates well with excisional pathology. This constitutes strong ground for increasingly used renal mass biopsy in patients considering active surveillance or ablation therapy. PMID- 26811389 TI - The Current Status of Solitary Fibrous Tumor: Diagnostic Features, Variants, and Genetics. AB - Solitary fibrous tumor (SFT) is a fibroblastic mesenchymal tumor originally described in the pleura but now shown at almost every anatomic site. Histopathologically, SFT is characteristically a circumscribed neoplasm composed of variably cellular and patternless distributions of bland spindle and ovoid cells within prominent collagenous stroma and shows diffuse expression of CD34, but it has a broad spectrum of both morphology and of biologic behavior. Many different names (particularly hemangiopericytoma) were previously used in the course of our understanding of this neoplasm but are now subsumed under the term "SFT," and the putative cell of origin was debated. However, it is now recognized that SFT is a translocation-associated neoplasm, consistently associated with NAB2-STAT6 gene fusions arising from recurrent intrachromosomal rearrangements on chromosome 12q, and this translocation is a likely major contributor to its pathogenesis. While most SFT with classical morphologic features behave in an indolent manner and those with overtly malignant histologic features tend to be aggressive neoplasms that behave as high-grade sarcomas, the behavior of SFT is unpredictable, and it is important to be aware of the propensity for aggressive behavior in a minority of histologically classical SFT and to ensure adequate clinical follow-up. Surgical excision remains the treatment gold standard; while radiotherapy and conventional chemotherapeutic agents have only shown limited efficacy, further understanding of the molecular events underlying tumorigenesis may allow the development of novel targeted treatments. We review SFT, discussing the morphologic spectrum and variants, including malignant and dedifferentiated subtypes, clinicopathological aspects, recent molecular genetic findings, and the differential diagnosis. PMID- 26811390 TI - Congenital coronary artery anomalies: a bridge from embryology to anatomy and pathophysiology--a position statement of the development, anatomy, and pathology ESC Working Group. AB - Congenital coronary artery anomalies are of major significance in clinical cardiology and cardiac surgery due to their association with myocardial ischaemia and sudden death. Such anomalies are detectable by imaging modalities and, according to various definitions, their prevalence ranges from 0.21 to 5.79%. This consensus document from the Development, Anatomy and Pathology Working Group of the European Society of Cardiology aims to provide: (i) a definition of normality that refers to essential anatomical and embryological features of coronary vessels, based on the integrated analysis of studies of normal and abnormal coronary embryogenesis and pathophysiology; (ii) an animal model-based systematic survey of the molecular and cellular mechanisms that regulate coronary blood vessel development; (iii) an organization of the wide spectrum of coronary artery anomalies, according to a comprehensive anatomical and embryological classification scheme; (iv) current knowledge of the pathophysiological mechanisms underlying symptoms and signs of coronary artery anomalies, with diagnostic and therapeutic implications. This document identifies the mosaic-like embryonic development of the coronary vascular system, as coronary cell types differentiate from multiple cell sources through an intricate network of molecular signals and haemodynamic cues, as the necessary framework for understanding the complex spectrum of coronary artery anomalies observed in human patients. PMID- 26811392 TI - Nurses' and patients' perceptions of privacy protection behaviours and information provision. AB - BACKGROUND: With increased attention to patient privacy and autonomy, privacy protection and information provision for patients are becoming increasingly important. OBJECTIVES: The aim of this study was to identify and analyse nurses' and patients' perceptions of the importance and performance of protecting patients' privacy and providing them with relevant information. RESEARCH DESIGN: This study is a descriptive cross-sectional investigation. Participants and research context: Participants were 168 patients hospitalised in medical and surgical wards and 176 nurses who cared for them. Ethical consideration: This study was approved by the Chung-Ang University Bioethics Committee, and informed written consent was collected from all participants. FINDINGS: Nurses' recognition of the importance of protecting patients' privacy and providing adequate information was higher compared to their actual performance, and the nurses' level of performance was higher in comparison with the patients' recognition of its importance. DISCUSSION: Although a holistic approach to patient privacy protection and information provision is needed, the medical field has not embraced this model of care. CONCLUSIONS: These findings provide empirical data to create an ethical environment for the future, as considerable attention has been devoted to patients' rights and medical institutions' liability for providing explanations to patients. PMID- 26811391 TI - General and Genetic Toxicology of Guayusa Concentrate (Ilex guayusa). AB - Tea from the leaves of guayusa (Ilex guayusa) has a long history of consumption by Ecuadorian natives in regions where the plant is indigenous. The tea contains the methylxanthines caffeine and theobromine as well as chlorogenic acids, flavonoids, and sugars. Various studies were performed to evaluate the general and genetic toxicology of a standardized liquid concentrate of guayusa (GC). Guayusa concentrate was found to be negative in in vitro genotoxicity tests including the Ames test and a chromosome aberration study in human lymphocytes. The oral median lethal dose (LD50) of GC was >5,000 mg/kg for female rats. Guayusa concentrate was administered to male and female rats in a 90-day subchronic study at 1,200, 2,500, and 5,000 mg/kg/d of GC and a caffeine-positive control at 150 mg/kg/d corresponding to the amount of caffeine in the high-dose GC group. Effects observed in the GC-treated groups were comparable to those in the caffeine control group and included reductions in body weights, food efficiency, triglycerides values, and fat pad weights and increases in blood chemistry values for serum aspartate aminotransferase, serum alanine aminotransferase, and cholesterol and adaptive salivary gland hypertrophy. No signs of incremental toxicity due to any other components of guayusa were observed. The studies indicate no harmful effects of GC in these test systems. PMID- 26811393 TI - Effects of ethics education on moral sensitivity of nursing students. AB - BACKGROUND: While nursing ethics education is commonly provided for undergraduate nursing students in most nursing colleges, consensus on the content and teaching modules for these ethics courses have still not been established. OBJECTIVES: This study aimed to examine the effects of nursing ethics education on the moral sensitivity and critical thinking disposition of nursing students in Korea. RESEARCH DESIGN: A one-group pre- and post-test design was used. Moral sensitivity was measured using the Korean version of the Moral Sensitivity Questionnaire. Critical thinking disposition was measured using the Critical Thinking Disposition Questionnaire. Participants and research context: Participants were 70 undergraduate nursing students who were attending a university located in Seoul, Korea. The nursing ethics education was provided 7 times, from September to December 2010, and comprised 90-min sessions each week. Ethical considerations: This study was conducted in accordance with the Human Subject Research Ethics Committee guidelines. FINDINGS: After the education, the levels for the patient-oriented care, a sub-domain of moral sensitivity, and inquisitiveness, a sub-domain of critical thinking disposition, significantly improved. There were no changes in overall scores for moral sensitivity and critical thinking disposition. There were significant positive correlations between moral sensitivity and critical thinking disposition both pre- and post intervention. CONCLUSION: These results reflect the need for ongoing efforts to develop innovative content, structure, and instructional methods for undergraduate nursing ethics education programs. PMID- 26811394 TI - From painful busyness to emotional immunization: Nurses' experiences of ethical challenges. AB - BACKGROUND: The professional values presented in ethical guidelines of the Norwegian Nurses Organisation and International Council of Nurses describe nurses' professional ethics and the obligations that pertain to good nursing practice. The foundation of all nursing shall be respect for life and the inherent dignity of the individual. Research proposes that nurses lack insight in ethical competence and that ethical issues are rarely discussed on the wards. Furthermore, research has for some time confirmed that nurses experience moral distress in their daily work and that this has become a major problem for the nursing profession. OBJECTIVES: The purpose of this article is to obtain a deeper understanding of the ethical challenges that nurses face in daily practice. The chosen research questions are "What ethical challenges do nurses experience in their daily practice?" RESEARCH DESIGN: We conducted a qualitative interview study using a hermeneutical approach to analyzing data describing nurses' experiences. Ethical considerations: The Norwegian Social Science Data services approved the study. Furthermore, the head of the hospital gave permission to conduct the investigation. The requirement of anonymity and proper data storage in accordance with the World Medical Association Declaration of Helsinki was met. METHOD AND RESULTS: The context for the study comprised three different clinical wards at a university hospital in Norway. Nine qualified nurses were interviewed. The results were obtained through a systematic development beginning with the discovery of busyness as a painful phenomenon that can lead to conflicts in terms of ethical values. Furthermore, the consequences compromising professional principles in nursing care emerged and ended in moral blindness and emotional immunization of the healthcare providers. Emotional immunization occurred as a new dimension involving moral blindness and immunity in relation to being emotionally touched. PMID- 26811395 TI - Evaluating care from a care ethical perspective:: A pilot study. AB - BACKGROUND: Care ethical theories provide an excellent opening for evaluation of healthcare practices since searching for (moments of) good care from a moral perspective is central to care ethics. However, a fruitful way to translate care ethical insights into measurable criteria and how to measure these criteria has as yet been unexplored: this study describes one of the first attempts. OBJECTIVE: To investigate whether the emotional touchpoint method is suitable for evaluating care from a care ethical perspective. RESEARCH DESIGN: An adapted version of the emotional touchpoint interview method was used. Touchpoints represent the key moments to the experience of receiving care, where the patient recalls being touched emotionally or cognitively. Participants and research context: Interviews were conducted at three different care settings: a hospital, mental healthcare institution and care facility for older people. A total of 31 participants (29 patients and 2 relatives) took part in the study. Ethical considerations: The research was found not to be subject to the (Dutch) Medical Research Involving Human Subjects Act. FINDINGS: A three-step care ethical evaluation model was developed and described using two touchpoints as examples. A focus group meeting showed that the method was considered of great value for partaking institutions in comparison with existing methods. Reflection and discussion: Considering existing methods to evaluate quality of care, the touchpoint method belongs to the category of instruments which evaluate the patient experience. The touchpoint method distinguishes itself because no pre defined categories are used but the values of patients are followed, which is an essential issue from a care ethical perspective. The method portrays the insider perspective of patients and thereby contributes to humanizing care. CONCLUSION: The touchpoint method is a valuable instrument for evaluating care; it generates evaluation data about the core care ethical principle of responsiveness. PMID- 26811396 TI - Relationship-based nursing care and destructive demands. AB - BACKGROUND: The relationship between the nurse and the patient is understood as fundamental in nursing care. However, numerous challenges can be related to the provision of relationship-based nursing care. Challenges exist when nurses do not respond adequately to the patient's appeal for help. Moreover, challenges arising in the nurse-patient relationship can be understood as more destructive demands from the patient to the nurse, thus begging inquiry into such a relationship. RESEARCH QUESTION: The overall aim is to explore and argue the relevance of problematizing destructive demands evident within relationship-based nursing care. RESEARCH DESIGN: This theoretical article explores destructive demands based on the phenomenological philosophy of the Danish theologian and philosopher Knud E. Logstrup and provides examples of nurses' experiences in everyday nursing care. The examples are drawn from a Norwegian empirical study based on a hermeneutical research design. Participants and research context: Data consisted of qualitative interviews and qualitative follow-up interviews with 13 nurses with varying work experience within the primary and secondary somatic and psychiatric health service, from inside as well as outside institutions. Ethical consideration: The original empirical study was approved by the Norwegian Social Science Data Services. Information was given and consent was obtained from the participants. FINDINGS: Two themes are described: strong impressions formed in meetings with patients and persistent concern over the burden of work and ability to endure. DISCUSSION: Destructive demands related to relationship-based nursing care are discussed along two lines, first, by further elucidating nurses' everyday experiences connected to destructive demands and, second, by highlighting the significance of including destructive demands within the relationship-based nursing care. CONCLUSION: Including destructive demands related to relationship-based nursing care is of particular significance in enabling the proposition that radical, one-sided demands are based on relationality, reciprocity and thereby expectations of life. In short, both the nurse and the patient are human beings in need of love and goodness. PMID- 26811397 TI - Professional values, job satisfaction, career development, and intent to stay. AB - BACKGROUND: Hospitals are experiencing an estimated 16.5% turnover rate of registered nurses costing from $44,380 - $63,400 per nurse-an estimated $4.21 to $6.02 million financial loss annually for hospitals in the United States of America. Attrition of all nurses is costly. Most past research has focused on the new graduate nurse with little focus on the mid-career nurse. Attrition of mid career nurses is a loss for the profession now and into the future. RESEARCH OBJECTIVE: The purpose of the study was to explore relationships of professional values orientation, career development, job satisfaction, and intent to stay in recently hired mid-career and early-career nurses in a large hospital system. RESEARCH DESIGN: A descriptive correlational study of personal and professional factors on job satisfaction and retention was conducted. Participants and research context: A convenience sample of nurses from a mid-sized hospital in a metropolitan area in the Southwestern United States was recruited via in-house email. Sixty-seven nurses met the eligibility criteria and completed survey documents. Ethical considerations: Institutional Review Board approval was obtained from both the university and hospital system. FINDINGS: Findings indicated a strong correlation between professional values and career development and that both job satisfaction and career development correlated positively with retention. DISCUSSION: Newly hired mid-career nurses scored higher on job satisfaction and planned to remain in their jobs. This is important because their expertise and leadership are necessary to sustain the profession into the future. CONCLUSION: Nurse managers should be aware that when nurses perceive value conflicts, retention might be adversely affected. The practice environment stimulates nurses to consider whether to remain on the job or look for other opportunities. PMID- 26811398 TI - Against dichotomies: On mature care and self-sacrifice in care ethics. AB - INTRODUCTION: In previous issues of this journal, Carol Gilligan's original concept of mature care has been conceptualized by several (especially Norwegian) contributors. This has resulted in a dichotomous view of self and other, and of self-care and altruism, in which any form of self-sacrifice is rejected. Although this interpretation of Gilligan seems to be quite persistent in care-ethical theory, it does not seem to do justice to either Gilligan's original work or the tensions experienced in contemporary nursing practice. DISCUSSION: A close reading of Gilligan's concept of mature care leads to a view that differs radically from any dichotomy of self-care and altruism. Instead of a dichotomous view, a dialectical view on self and other is proposed that builds upon connectedness and might support a care-ethical view of nursing that is more consistent with Gilligan's own critical insights such as relationality and a practice-based ethics. A concrete case taken from nursing practice shows the interconnectedness of professional and personal responsibility. This underpins a multilayered, complex view of self-realization that encompasses sacrifices as well. CONCLUSION: When mature care is characterized as a practice of a multilayered connectedness, caregivers can be acknowledged for their relational identity and nursing practices can be recognized as multilayered and interconnected. This view is better able to capture the tensions that are related to today's nursing as a practice, which inevitably includes sacrifices of self. In conclusion, a further discussion on normative conceptualizations of care is proposed that starts with a non-normative scrutiny of caring practices. PMID- 26811399 TI - Violence against new graduated nurses in clinical settings: A qualitative study. AB - BACKGROUND: Ethical studies in nursing are very important topics, and it is particularly crucial with vulnerable populations such as new graduated nurses. Neglecting ethical principles and violence toward graduates can lead to their occupational burnout, job dissatisfaction, and leaving the nursing profession. OBJECTIVE: This study was designed with the aim of understanding the experience of Iranian experienced nurses' use of lateral and horizontal violence against new graduated nurses. RESEARCH DESIGN: This qualitative study used a conventional content analysis approach; it was conducted with 18 experienced nurses. Data were collected through unstructured and semi-structured interviews of various general hospital departments in northwest of Iran and analyzed using methods as described by Graneheim and Lundman. Ethical considerations: This study was approved by the Regional Committee of Medical Research Ethics. The ethical principles of voluntary participation, anonymity, and confidentiality were considered. FINDINGS: "Psychological violence," "Verbal violence," "Physical violence," and "Source of violence" were four categories extracted through data analysis. DISCUSSION: Violence behaviors are instances of workplace maltreatment that damage individual nurses, quality of care, and the ethical climate of the healthcare settings. The lateral and hierarchical violence in nursing were explained by oppressed group model. CONCLUSION: This study provided the context for identifying details of various types of workplace violence against new graduated nurses. It should be approached as a health system priority that requires specific multi-dimensional methods to manage consisting of identification, strategic planning, policymaking, prevention, education, and research. PMID- 26811400 TI - Dignity in long-term care: An application of Nordenfelt's work. AB - BACKGROUND: The concept of dignity is recognised as a fundamental right in many countries. It is embedded into law, human rights legislation and is often visible in organisations' philosophy of care, particularly in aged care. Yet, many authors describe difficulties in defining dignity and how it can be preserved for people living in long term care. OBJECTIVES: In this article, Nordenfelt's 'four notions of dignity' are considered, drawing on research literature addressing the different perspectives of those who receive, observe or deliver care in the context of the long-term care environment. METHODS: A review of the literature was undertaken using the terms 'nursing homes', 'residential care' or 'long-term care'. The terms were combined and the term 'human dignity' was added. A total of 29 articles met the inclusion criteria from the United Kingdom (14), United States (2), Australia (1), Sweden (3), Hong Kong (2), Norway (3), Nordic (1), Taiwan (1), Netherlands (1). Ethical Considerations: Every effort has been made to ensure an unbiased search of the literature with the intention of an accurate interpretation of findings. DISCUSSION: The four notions of dignity outlined by Nordenfelt provide a comprehensive description of the concept of dignity which can be linked to the experiences of people living in long-term care today and provide a useful means of contextualising the experiences of older people, their families and significant others and also of staff in long-term care facilities. Of particular interest are the similarities of perspectives of dignity between these groups. The preservation of dignity implies that dignity is a quality inherent in us all. This links directly to the exploration and conclusions drawn from the literature review. Conversely, promoting dignity implies that dignity is something that can be influenced by others and external factors. Hence, there are a number of implications for practice. CONCLUSION: We suggest that two of Nordenfelt's notions, 'dignity of identity' and 'dignity of Menschenwude', are a common thread for residents, family members and staff when conceptualising dignity within long-term care environments. PMID- 26811401 TI - Ethical and cultural striving: Lived experiences of minority nurses in dementia care. AB - BACKGROUND: Nursing workforce in Western European health institutions has become more diverse because of immigration and recruitment from Asian, African, and East European countries. Minority healthcare providers may experience communication problems in interaction with patients and coworkers, and they are likely to experience conflict or uncertainty when confronted with different cultural traditions and values. Persons with dementia are a vulnerable group, and the consequences of their illness challenge the ability to understand and express oneself verbally. The large number of minority healthcare providers in nursing homes underlines the importance to obtain better knowledge about this group's experiences with the care challenges in dementia care units. RESEARCH QUESTION: Can you tell about any challenges in the experiences in the encounter with persons suffering from dementia? Participants and research context: Five minority healthcare providers in a nursing home, in a dementia unit. All guidelines for research ethic were followed. Ethical consideration: The participants were informed that participation was voluntary, and they were guarantied anonymity. METHOD: We used a qualitative method, conducting individual interviews, using a narrative approach. In the analysis, we applied a phenomenological-hermeneutical method, developed for researching life experiences. FINDINGS: One theme and four subthemes: striving to understand the quality of care for persons with dementia. The subthemes: sensitivity to understand the patients' verbal and nonverbal expressions. To understand gratefulness, understand the patient as an adult and autonomous person, and understand the patient as a patient in a nursing home. Challenges comprise both ethical and cultural striving to understand persons with dementia. CONCLUSION: To care for persons with dementia in an unfamiliar context may be understood as a striving for acting ethically, when at the same time striving to adapt and acculturate to new cultural norms, in order to practice good dementia care. PMID- 26811402 TI - Quality versus quantity: The complexities of quality of life determinations for neonatal nurses. AB - BACKGROUND: The ability to save the life of an extremely premature baby has increased substantially over the last decade. This survival, however, can be associated with unfavourable outcomes for both baby and family. Questions are now being asked about quality of life for survivors of extreme prematurity. Quality of life is rightly deemed to be an important consideration in high technology neonatal care; yet, it is notoriously difficult to determine or predict. How does one define and operationalise what is considered to be in the best interest of a surviving extremely premature baby, especially when the full extent of the outcomes might not be known for several years? RESEARCH QUESTION: The research investigates the caregiving dilemmas often faced by neonatal nurses when caring for extremely premature babies. This article explores the issues arising for neonatal nurses when they considered the philosophical and ethical questions about quality of life in babies <=24 weeks gestation. PARTICIPANTS: Data were collected via a questionnaire to Australian neonatal nurses and semi-structured interviews with 24 neonatal nurses in New South Wales, Australia. Ethical considerations: Ethical processes and procedures have been adhered to by the researchers. FINDINGS: A qualitative approach was used to analyse the data. The theme 'difficult choices' was generated which comprised three sub-themes: 'damaged through survival', 'the importance of the brain' and 'families are important'. The results show that neonatal nurses believed that quality of life was an important consideration; yet they experienced significant inner conflict and uncertainty when asked to define or suggest specific elements of quality of life, or to suggest how it might be determined. It was even more difficult for the nurses to say when an extremely premature baby's life possessed quality. Their previous clinical and personal experiences led the nurses to believe that the quality of the family's life was important, and possibly more so than the quality of life of the surviving baby. This finding contrasts markedly with much of the existing literature in this field. CONCLUSION: Quality of life for extremely premature babies was an important consideration for neonatal nurses; however, they experienced difficulty deciding how to operationalise such considerations in their everyday clinical practice. PMID- 26811403 TI - Response of metastatic mucosal melanoma to immunotherapy: It can get worse before it gets better. AB - Immune therapy with checkpoint inhibitors has revolutionized the management of metastatic melanoma. Ipilimumab, nivolumab, and pembrolizumab are all FDA approved immune checkpoint inhibitors to treat metastatic melanoma. Responses to immune checkpoint inhibitors are usually delayed. An interim progression on restaging computed tomography scans "pseudo-progression" may be observed before response to treatment occur. In this case, we report a significant interim progression of metastatic mucosal melanoma before meaningful responses to immunotherapy occurred. The patient developed significant immune therapy-related colitis and new onset vitiligo. Further restaging computed tomography scans showed sustained tumor response despite stopping the immune therapy. PMID- 26811404 TI - Taxane-induced arthralgia and myalgia: A literature review. AB - Purpose Arthralgia and myalgia following taxane chemotherapy has been documented in the literature. However, these two toxicities associated with taxane treatment have not been closely examined in the literature, and data remain inconsistent in terms of the reported incidences of these toxicities. The purpose of this literature review was to provide a more comprehensive understanding of the incidence of taxane-induced arthralgia and myalgia, as well as to document the risk factors and preventative and therapeutic treatments that have been investigated. Methods A literature search was conducted in Ovid Medline, OldMedline, Embase, Embase Classic, and Cochrane Central Register of Controlled Trials using relevant subject headings and keywords such as: "arthralgia," "myalgia," "muscle pain," "joint pain," "taxane," "chemotherapy," "docetaxel," "paclitaxel." Results The reported incidences of arthralgia and myalgia were variable. Taxane chemotherapy was found to be associated with greater incidences of arthralgia and myalgia than non-taxane forms of chemotherapy. Moreover, docetaxel and nab-paclitaxel seem to be associated with lower incidences of arthralgia and myalgia than paclitaxel. Finally, the literature on prevention and therapeutic treatment of taxane-induced arthralgia and myalgia is scarce. Conclusion More studies should be done in order to more conclusively identify optimal therapeutic and preventative treatments as well as different risk factors. We recommend that a prospective study be done in order to better understand the true incidence of arthralgia and myalgia in patients being treated with the paclitaxel, docetaxel, and nab-paclitaxel. PMID- 26811405 TI - MECHANISMS IN ENDOCRINOLOGY: New concepts to further unravel adrenal insufficiency during critical illness. AB - The concept of 'relative' adrenal insufficiency during critical illness remains a highly debated disease entity. Several studies have addressed how to diagnose or treat this condition but have often yielded conflicting results, which further fuelled the controversy. The main reason for the controversy is the fact that the pathophysiology is not completely understood. Recently, new insights in the pathophysiology of the hypothalamic-pituitary-adrenal axis response to critical illness were generated. It was revealed that high circulating levels of cortisol during critical illness are explained more by reduced cortisol breakdown than by elevated cortisol production. Cortisol production rate during critical illness is less than doubled during the day but lower than in healthy subjects during the night. High plasma cortisol concentrations due to reduced breakdown in turn reduce plasma ACTH concentrations via feedback inhibition, which with time may lead to an understimulation and hereby a dysfunction of the adrenal cortex. This could explain the high incidence of adrenal insufficiency in the prolonged phase of critical illness. These novel insights have created a new framework for the diagnosis and treatment of adrenal failure during critical illness that has redirected future research. PMID- 26811406 TI - Reduction in daily hydrocortisone dose improves bone health in primary adrenal insufficiency. AB - OBJECTIVE: Individuals with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) receive life-long glucocorticoid (GC) replacement therapy. Current daily GC doses are still higher than the reported adrenal cortisol production rate. This GC excess could result in long-term morbidities such as osteoporosis. No prospective trials have investigated the long-term effect of GC dose changes in PAI and CAH patients. METHODS: This is a prospective and longitudinal study including 57 subjects with PAI (42 women) and 33 with CAH (21 women). Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry at baseline and after 2 years. Subjects were divided into three groups (similar baseline characteristics) depending on changes in daily hydrocortisone equivalent dose (group 1: unchanged 25.2+/-8.2 mg (mean+/-S.D., n=50); group 2: increased 18.7+/-10.3 to 25.9+/-12.0 mg (n=13); group 3: decreased 30.8+/-8.5 to 21.4+/-7.2 mg (n=27)). RESULTS: Subjects in group 1 showed normal lumbar and femoral Z-scores which were unchanged over time. Group 2 subjects showed a significant decrease in femoral neck Z-scores over time ( 0.15+/-1.1 to -0.37+/-1.0 (P<0.05)), whereas group 3 subjects showed a significant increase in lumbar spine and hip Z-scores (L1-L4: -0.93+/-1.2 to 0.65+/-1.5 (P<0.05); total hip: -0.40+/-1.0 to -0.28+/-1.0 (P<0.05)). No changes in BMI over time were seen within any group. Reduction in GC dose did not increase the risk of adrenal crisis. CONCLUSION: This study demonstrates for the first time that cautious reduction in hydrocortisone equivalent doses leads to increases in BMD, whereas dose increments reduced BMD. These data emphasize the need for the lowest possible GC replacement dose in AI patients to maintain health and avoid long-term adverse effects. PMID- 26811407 TI - Clinicopathological predictive factors in the early remission of corticotroph pituitary macroadenomas in a tertiary referral centre. AB - OBJECTIVE: Corticotroph macroadenomas are a rare cause of Cushing's disease (CD), but their properties are not well-recognised. The aim of this study was to evaluate the clinical and pathological aspects of corticotroph macroadenomas with particular emphasis on proliferation markers and their associations with the efficacy of surgical treatment. DESIGN: A prospective cohort study was conducted in a tertiary referral centre in Poland. METHODS: In total, 59 patients with CD (20 macroadenomas and 39 microadenomas) were included in this study. Hormonal and imaging parameters, histopathological and ultrastructural features of the corticotroph tumours and the early surgical outcomes were evaluated. RESULTS: ACTH and ACTH/cortisol ratios were higher in macroadenomas (P<0.001 and P=0.002 respectively). Greater tumour volumes were associated with higher Ki-67 and p53 expression (Ptrend=0.009 and Ptrend=0.024 respectively) and the rates of sparsely granulated adenomas (Ptrend=0.036). Immediate postoperative remission and early biochemical remission rates were lower in macroadenomas compared to microadenomas (P<0.001). A logistic regression model showed that the immediate postoperative remission or early biochemical remission depended on tumour volume (P=0.005 and P=0.006 respectively) and invasiveness based on Knosp grades 3 and 4 for macroadenomas and a lack of surgical pseudocapsule for microadenomas (P=0.004 and P=0.007 respectively). CONCLUSION: Corticotroph macroadenomas differ from the more common microadenomas not only in terms of hormonal and imaging characteristics but also in terms of immunohistochemical and ultrastructural features and proliferation markers. The early effectiveness of surgery depends primarily on tumour volume and invasiveness. PMID- 26811408 TI - Osteopontin expression is correlated with differentiation and good prognosis in medullary thyroid carcinoma. AB - BACKGROUND: Osteopontin (OPN) or secreted phosphoprotein 1 (SPP1) is a matricellular glycoprotein whose expression is elevated in various types of cancer and has been shown to be involved in tumourigenesis and metastasis in many malignancies, including follicular cell-derived thyroid carcinomas. Its role in C cell-derived thyroid lesions and tumours remains to be established. OBJECTIVE: The objective of this study is to clarify the role of OPN expression in the development of medullary thyroid carcinoma (MTC). METHODS: OPN expression was analysed in a series of 116 MTCs by immunohistochemistry and by qPCR mRNA quantification of the 3 OPN isoforms (OPNa, OPNb and OPNc) in six cases from which fresh frozen tissue was available. Statistical tests were used to evaluate the relationship of OPN expression and the clinicopathological and molecular characteristics of patients and tumours. RESULTS: OPN expression was detected in 91 of 116 (78.4%) of the MTC. We also observed high OPN expression in C-cell hyperplasia as well as in C-cells scattered in the thyroid parenchyma adjacent to the tumours. OPN expression was significantly associated with smaller tumour size, PTEN nuclear expression and RAS status, and suggestively associated with non-invasive tumours. OPNa isoform was expressed significantly at higher levels in tumours than in non-tumour samples. OPNb and OPNc presented similar levels of expression in all samples. Furthermore, OPNa isoform overexpression was significantly associated with reduced growth and viability in the MTC-derived cell line (TT). CONCLUSION: The expression of OPN in normal C-cells and C-cell hyperplasia suggests that OPN is a differentiation marker of C-cells, rather than a marker of biological aggressiveness in this setting. At variance with other cancers, OPN expression is associated with good prognostic features in MTC. PMID- 26811409 TI - Serum levels of thyroid hormones and thyroid stimulating hormone in patients with biliogenic and hyperlipidaemic acute pancreatitis: Difference and value in predicting disease severity. AB - OBJECTIVES: To compare retrospectively serum levels of thyroid hormones (THs) and thyroid stimulating hormone (TSH) between patients with biliogenic acute pancreatitis (BAP) and those with hyperlipidaemic acute pancreatitis (HLAP), in order to assess their value for predicting the severity of acute pancreatitis (AP). METHODS: Patients with AP were divided into BAP and HLAP groups, then further divided into either a mild AP (MAP) group or a moderately severe AP (MSAP) group. Routine blood parameters were measured. Free tri-iodothyronine (FT3), free thyroxine (FT4) and TSH levels were measured. RESULTS: Seventy-six patients with AP were enrolled in the study. FT3 and TSH levels were significantly higher in patients with MAP than in patients with MSAP. FT4 and TSH levels were significantly lower in the HLAP group than in the BAP group. TSH levels in both MAP and MSAP patients were significantly lower in the HLAP group than in the BAP group. TSH was inversely correlated with triglyceride levels in patients with HLAP. FT3 was a risk factor for MSAP in patients with AP and also demonstrated moderate accuracy in predicting AP severity. CONCLUSIONS: THs and TSH decrease with the severity of AP, especially in patients with HLAP. FT3 may be a useful biomarker for the early assessment of the severity of AP. PMID- 26811410 TI - Specific behavioural phenotype and secondary cognitive decline as a result of an 8.6 Mb deletion of 2q32.2q33.1. AB - Chromosomal abnormalities involving 2q32q33 deletions are very rare and present with a specific phenotype. This case report describes a 37-year-old female patient with 2q32q33 microdeletion syndrome presenting with the characteristic features, but with the addition of secondary cognitive decline. Molecular karyotyping was performed on the patient and her parents. It revealed an 8.6 megabase deletion with the proximal breakpoint in the chromosome band 2q32.2 and the distal breakpoint in 2q33.1. The deletion encompassed 22 known genes, including theGLS,MYO1B,TMEFF2,PGAP1andSATB2genes. The observed deletion was confirmed using a paralogue ratio test. This case report provides further evidence that theSATB2gene, together withGLS,MYO1B,TMEFF2and possiblyPGAP1,is a crucial gene in 2q32q33 microdeletion syndrome. TheSATB2gene seems to be crucial for the behavioural problems noted in our case, but deletion of theGLS,MYO1BandTMEFF2genes presumably contributed to the more complex behavioural characteristics observed. Our patient is also, to our knowledge, the only patient with 2q32q33 microdeletion syndrome with secondary cognitive decline. PMID- 26811412 TI - Fat burn X: burning more than fat. AB - A 50-year-old man presented with a 2-day history of bilateral lower extremity cramping and dark urine. The patient was found to have a creatine phosphokinase (CPK) elevated of up to 2306 U/L, a serum uric acid of 9.7 mg/dL and 101 red blood cell's per high-powered field on urinalysis. On questioning, the patient endorsed daily exercise with free weights. There were no changes in his regular exercise and medication regimen, no muscle trauma, no recent drug use and no illness. The patient did mention using a new fat burner known as 'Fat Burn X', which he had begun taking 2 days prior to the onset of his muscle cramps. The patient was given normal saline intravenous fluid resuscitation for 48 h with resultant normalisation of his CPK and creatinine, and was discharged with primary care follow-up. PMID- 26811414 TI - Hyperphosphatemic tumoural calcinosis. PMID- 26811411 TI - Challenges of diagnosis and management of axial spondyloarthritis in North Africa and the Middle East: An expert consensus. AB - Axial spondyloarthritis (SpA) is a spectrum of inflammatory disease with stages characterized by both nonradiographic and radiographic sacroiliitis. Nonradiographic axial SpA is associated with health-related quality-of-life impairment and may progress to ankylosing spondylitis. Axial SpA has a low prevalence in some countries in North Africa and the Middle East, and pooling of data and resources is needed to increase understanding of the regional picture. Early diagnosis and effective treatment are required to reduce disease burden and prevent progression. Anti-TNF therapy is recommended for patients with persistently high disease activity despite conventional treatment, and has been shown to be effective in patients without radiographic damage. Diagnostic delays can be an obstacle to early treatment and appropriate referral strategies are needed. In some countries, restricted access to magnetic resonance imaging and anti-TNF agents presents a challenge. In this article, a group of experts from North Africa and the Middle East evaluated the diagnosis and management of axial SpA with particular reference to this region. PMID- 26811413 TI - Parvovirus leading to thrombotic microangiopathy in a healthy adult. AB - A healthy 47-year-old man initially presented with symptoms of body rash, myalgias, dark urine, nausea and vomiting. Acute kidney injury, and positive urine analysis for blood and protein warranted a kidney biopsy, which revealed micro thrombi in kidney vasculature, suggestive of thrombotic microangiopathy. Serology revealed positive parvovirus B19 IgM antibodies and biopsy tests revealed a viral genome on PCR. Despite plasma exchanges and treatment with rituximab, renal function continued to deteriorate to end-stage renal disease. PMID- 26811415 TI - Global pseudo-atrial flutter ECG appearance secondary to unilateral parkinsonian tremor. PMID- 26811416 TI - Benign pineal cyst lined with normal choroid plexus mimicking tumour in a young girl with exotropia. PMID- 26811417 TI - The Path Forward on Endocrine Disruptors Requires Focus on the Basics. PMID- 26811418 TI - More than Manuscripts: Reproducibility, Rigor, and Research Productivity in the Big Data Era. PMID- 26811419 TI - The Influence of Selective and Divided Attention on Audiovisual Integration in Children. AB - This article aims to investigate whether there is a difference in audiovisual integration in school-aged children (aged 6 to 13 years; mean age = 9.9 years) between the selective attention condition and divided attention condition. We designed a visual and/or auditory detection task that included three blocks (divided attention, visual-selective attention, and auditory-selective attention). The results showed that the response to bimodal audiovisual stimuli was faster than to unimodal auditory or visual stimuli under both divided attention and auditory-selective attention conditions. However, in the visual selective attention condition, no significant difference was found between the unimodal visual and bimodal audiovisual stimuli in response speed. Moreover, audiovisual behavioral facilitation effects were compared between divided attention and selective attention (auditory or visual attention). In doing so, we found that audiovisual behavioral facilitation was significantly difference between divided attention and selective attention. The results indicated that audiovisual integration was stronger in the divided attention condition than that in the selective attention condition in children. Our findings objectively support the notion that attention can modulate audiovisual integration in school aged children. Our study might offer a new perspective for identifying children with conditions that are associated with sustained attention deficit, such as attention-deficit hyperactivity disorder. PMID- 26811420 TI - The 2015 advanced life support guidelines: a summary and evidence for the updates. AB - The International Liaison Committee on Resuscitation recently released updated 2015 recommendations for resuscitation. The guidelines form the basis for all levels of resuscitation training, now from first aid to advanced life support (ALS), and for trainees of varying medical skills, from schoolchildren to medical students and consultants. We highlight major updates relating to intra-arrest and postarrest care, and the evidence for their recommendation. We also summarise areas of uncertainty in the evidence for ALS, and highlight current discussions that will likely inform the next round of recommendations. PMID- 26811421 TI - TOPBP1 regulates RAD51 phosphorylation and chromatin loading and determines PARP inhibitor sensitivity. AB - Topoisomerase IIbeta-binding protein 1 (TOPBP1) participates in DNA replication and DNA damage response; however, its role in DNA repair and relevance for human cancer remain unclear. Here, through an unbiased small interfering RNA screen, we identified and validated TOPBP1 as a novel determinant whose loss sensitized human cells to olaparib, an inhibitor of poly(ADP-ribose) polymerase. We show that TOPBP1 acts in homologous recombination (HR) repair, impacts olaparib response, and exhibits aberrant patterns in subsets of human ovarian carcinomas. TOPBP1 depletion abrogated RAD51 loading to chromatin and formation of RAD51 foci, but without affecting the upstream HR steps of DNA end resection and RPA loading. Furthermore, TOPBP1 BRCT domains 7/8 are essential for RAD51 foci formation. Mechanistically, TOPBP1 physically binds PLK1 and promotes PLK1 kinase mediated phosphorylation of RAD51 at serine 14, a modification required for RAD51 recruitment to chromatin. Overall, our results provide mechanistic insights into TOPBP1's role in HR, with potential clinical implications for cancer treatment. PMID- 26811422 TI - Peroxisomes move by hitchhiking on early endosomes using the novel linker protein PxdA. AB - Eukaryotic cells use microtubule-based intracellular transport for the delivery of many subcellular cargos, including organelles. The canonical view of organelle transport is that organelles directly recruit molecular motors via cargo-specific adaptors. In contrast with this view, we show here that peroxisomes move by hitchhiking on early endosomes, an organelle that directly recruits the transport machinery. Using the filamentous fungus Aspergillus nidulans we found that hitchhiking is mediated by a novel endosome-associated linker protein, PxdA. PxdA is required for normal distribution and long-range movement of peroxisomes, but not early endosomes or nuclei. Using simultaneous time-lapse imaging, we find that early endosome-associated PxdA localizes to the leading edge of moving peroxisomes. We identify a coiled-coil region within PxdA that is necessary and sufficient for early endosome localization and peroxisome distribution and motility. These results present a new mechanism of microtubule-based organelle transport in which peroxisomes hitchhike on early endosomes and identify PxdA as the novel linker protein required for this coupling. PMID- 26811424 TI - TOPBP1 takes RADical command in recombinational DNA repair. AB - TOPBP1 is a key player in DNA replication and DNA damage signaling. In this issue, Moudry et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201507042) uncover a crucial role for TOPBP1 in DNA repair by revealing its requirement for RAD51 loading during repair of double strand breaks by homologous recombination. PMID- 26811425 TI - Mechanochemical ablation for symptomatic great saphenous vein reflux: A two-year follow-up. AB - Background Several studies have shown comparable early efficacy of mechanochemical ablation to endothermal techniques. The goal of this report was to show if early efficacy is maintained at 24 months. Methods This was a two-year analysis on the efficacy of mechanochemical ablation in patients with symptomatic C2 or more advanced chronic venous disease. Patients with reflux in the great saphenous vein involving the sapheno-femoral junction and no previous venous interventions were included. Demographic information, clinical, and procedural data were collected. The occlusion rate of treated veins was assessed with duplex ultrasound. Patient clinical improvement was assessed by Clinical-Etiology Anatomy-Pathophysiology (CEAP) class and venous clinical severity score. Results Of the initial 126 patients, there were 65 patients with 24 month follow-up. Of these 65 patients, 70% were female, with a mean age of 70 +/- 14 years and an average body mass index (BMI) of BMI of 30.5 +/- 6. The mean great saphenous vein diameter in the upper thigh was 7.6 mm and the mean treatment length was 39 cm. Adjunctive treatment of the varicosities was performed in 14% of patients during the procedure. Closure rates were 100% at one week, 98% at three months, 95% at 12 months, and 92% at 24 months. There was one patient with complete and four with partial recanalization ranging from 7 to 12 cm (mean length 9 cm). There was significant improvement in CEAP and venous clinical severity score (P < .001) for all time intervals. Conclusion Early high occlusion rate with mechanochemical ablation is associated with significant clinical improvement which is maintained at 24 months, making it a very good option for the treatment of great saphenous vein incompetence. PMID- 26811423 TI - Global reorganization of budding yeast chromosome conformation in different physiological conditions. AB - The organization of the genome is nonrandom and important for correct function. Specifically, the nuclear envelope plays a critical role in gene regulation. It generally constitutes a repressive environment, but several genes, including the GAL locus in budding yeast, are recruited to the nuclear periphery on activation. Here, we combine imaging and computational modeling to ask how the association of a single gene locus with the nuclear envelope influences the surrounding chromosome architecture. Systematic analysis of an entire yeast chromosome establishes that peripheral recruitment of the GAL locus is part of a large-scale rearrangement that shifts many chromosomal regions closer to the nuclear envelope. This process is likely caused by the presence of several independent anchoring points. To identify novel factors required for peripheral anchoring, we performed a genome-wide screen and demonstrated that the histone acetyltransferase SAGA and the activity of histone deacetylases are needed for this extensive gene recruitment to the nuclear periphery. PMID- 26811426 TI - Brazilian adult individuals with untreated isolated GH deficiency do not have accelerated subclinical atherosclerosis. AB - GH and its principal mediator IGF1 have important effects on metabolic and cardiovascular (CV) status. While acquired GH deficiency (GHD) is often associated with increased CV risk, the consequences of congenital GHD are not known. We have described a large group of patients with isolated GHD (IGHD) due to a homozygous mutation (c.57+1G>A) in the GH releasing hormone receptor gene, and shown that adult GH-naive individuals have no evidence of clinically evident premature atherosclerosis. To test whether subclinical atherosclerosis is anticipated in untreated IGHD, we performed a cross-sectional study of 25 IGHD and 27 adult controls matched for age and gender. A comprehensive clinical and biochemical panel and coronary artery calcium scores were evaluated by multi detector tomography. Height, weight, IGF1, homeostasis model assessment of insulin resistance, creatinine and creatininekinase were lower in the IGHD group. Median and interquartile range of calcium scores distribution was similar in the two groups: IGHD 0(0) and control 0(4.9). The vast majority of the calcium scores (20 of 25 IGHD (80%) and 18 of 27 controls (66.6%)) were equal to zero (difference not significant). There was no difference in the calcium scores classification. None of IGHD subjects had minimal calcification, which were present in four controls. Three IGHD and four controls had mild calcification. There were two IGHD individuals with moderate calcification and one control with severe calcification. Our study provides evidence that subjects with congenital isolated lifetime and untreated severe IGHD do not have accelerated subclinical coronary atherosclerosis. PMID- 26811428 TI - Imatinib reduces bone marrow fibrosis and overwhelms the adverse prognostic impact of reticulin formation in patients with chronic myeloid leukaemia. AB - AIMS: Before the era of tyrosine kinase inhibitors (TKIs), the presence of bone marrow fibrosis (MF) in patients with chronic myeloid leukaemia (CML) has been established as a poor prognostic factor. The aim of the present study was to evaluate the effects of imatinib treatment on MF and the prognostic significance of MF at this new era of CML therapy. METHODS: The study cohort consisted of 135 patients with CML who were exposed to imatinib. The grades of MF pre and post imatinib together with cytogenetic and molecular responses were evaluated. RESULTS: Severe MF (grade II-III) was observed in 44 (33%) patients prior to imatinib therapy, and in 8 (8%) after 12 months of imatinib treatment (p=0.001). The complete cytogenetic response (CCyR) rates at 12 months did not differ according to the pre-imatinib MF grades, and CCyR rates in patients with grades 0, I, II and III MF were 36/47 (76.5%), 26/33 (78.7%), 12/23 (52.1%) and 7/10 (70%), respectively (p=0.127). There was no significant difference between patients with or without CCyR at 12 months of imatinib regarding grades of MF (p=0.785). The distribution of the major molecular response rates at 18 months according to pre-treatment grades of MF were determined as grade 0 in 38/45 (84.4%), grade I in 21/28 (75%), grade II in 14/21 (66.6%) and grade III in 7/10 (70%) (p=0.112). There was no significant difference in overall survival rates between initial MF mild (grade 0-I) and severe (grade II-III) groups (p=0.278). CONCLUSIONS: According to our findings, MF regresses with imatinib therapy over time, and the MF grades at diagnosis do not have a negative impact on the responses to imatinib treatment. Therefore, the adverse prognostic impact of the MF among patients with CML seems to disappear in the era of the TKIs. PMID- 26811427 TI - Alcohol Use and Firearm Violence. AB - Although the misuse of firearms is necessary to the occurrence of firearm violence, there are other contributing factors beyond simply firearms themselves that might also be modified to prevent firearm violence. Alcohol is one such key modifiable factor. To explore this, we undertook a 40-year (1975-2014) systematic literature review with meta-analysis. One large group of studies showed that over one third of firearm violence decedents had acutely consumed alcohol and over one fourth had heavily consumed alcohol prior to their deaths. Another large group of studies showed that alcohol was significantly associated with firearm use as a suicide means. Two controlled studies showed that gun injury after drinking, especially heavy drinking, was statistically significant among self-inflicted firearm injury victims. A small group of studies investigated the intersection of alcohol and firearms laws and alcohol outlets and firearm violence. One of these controlled studies found that off-premise outlets selling takeout alcohol were significantly associated with firearm assault. Additional controlled, population level risk factor and intervention studies, including randomized trials of which only 1 was identified, are needed. Policies that rezone off-premise alcohol outlets, proscribe blood alcohol levels and enhance penalties for carrying or using firearms while intoxicated, and consider prior drunk driving convictions as a more precise criterion for disqualifying persons from the purchase or possession of firearms deserve further study. PMID- 26811429 TI - Angina severity predicts worse sleep quality after coronary artery bypass grafting. AB - OBJECTIVE: We sought to reveal whether the severity of angina pectoris affects sleep quality after elective coronary artery bypass grafting. MATERIAL AND METHODS: Patients scheduled to undergo isolated coronary artery bypass grafting were divided into two groups, having a recent myocardial infarction (Group 1, n=22, mean age 59.40+/-7.79 years) or not having a recent myocardial infarction (Group 2, n=30, mean age 59.73+/-7.72 years). The assessment included the Canadian Cardiovascular Society Angina Score, the visual analogue scale for postoperative pain and the Pittsburgh Sleep Quality Index (PSQI). RESULTS: The two groups were similar in regard to baseline characteristics. Cross-clamp time was significantly higher (p=0.007) and the use of inotropes was significantly more common (p=0.01) in those patients with recent myocardial infarction compared to those without. Mean Canadian Cardiovascular Society scores were also higher in patients with recent myocardial infarction (p=0.02). Total Pittsburgh Sleep Quality Index score was significantly higher in patients with recent myocardial infarction (8.45+/-3.50 vs. 5.03+/-2.32, respectively, p<0.001). In multivariate analysis, higher angina score (OR: 3.27, 95% CI, 1.20-8.90, p=0.02) and longer time of intensive care unit stay (OR: 6.15, 95% CI, 1.49-25.35, p=0.01) were found to be independent predictors of poor sleep quality. The Canadian Cardiovascular Society angina score showed a significant positive correlation with poor sleep duration score (<0.001), sleep disturbance score (p=0.02), day dysfunction due to sleepiness score (p=0.001), sleep efficiency score (p=0.003), overall sleep quality score (0.03) and total PSQI score (p=0.004). CONCLUSION: The severity of angina pectoris in the preoperative period is independently associated with worse sleep quality after elective isolated coronary artery bypass surgery. PMID- 26811431 TI - Effectiveness and Cost of Insecticide-Treated Bed Nets and Indoor Residual Spraying for the Control of Cutaneous Leishmaniasis: A Cluster-Randomized Control Trial in Morocco. AB - Cutaneous leishmaniasis (CL) remains an important public health problem in Morocco. A cluster-randomized trial was conducted with the following three study arms: 1) long-lasting insecticide-treated nets (LLINs) plus standard of care environmental management (SoC-EM), 2) indoor residual spraying (IRS) with alpha cypermethrin plus SoC-EM, and 3) SoC-EM alone. Incidence of new CL cases by passive and active case detection, sandfly abundance, and cost and cost effectiveness was compared between study arms over 5 years. Incidence of CL and sandfly abundance were significantly lower in the IRS arm compared with SoC-EM (CL incidence rate ratio = 0.32, 95% confidence interval [CI] = 0.15-0.69, P = 0.005 and sandfly abundance ratio = 0.39, 95% CI = 0.18-0.85, P = 0.022). Reductions in the LLIN arm of the study were not significant, possibly due to poor compliance. IRS was effective and more cost-effective for the prevention of CL in Morocco. PMID- 26811430 TI - In Vivo Efficacy and Parasite Clearance of Artesunate + Sulfadoxine-Pyrimethamine Versus Artemether-Lumefantrine in Mali. AB - Although artemisinin resistance has yet to be reported in Africa, surveillance of the efficacy of artemisinin-based combination therapies (ACTs) is warranted. Here, the efficacy of artesunate + sulfadoxine-pyrimethamine (AS + SP) and artemether-lumefantrine (AL) was evaluated in Mali. Randomized open-label comparative in vivo assay of AS + SP versus AL were carried out using the 28-day follow-up World Health Organization protocol. Patients with uncomplicated falciparum malaria and at least 6 months of age were recruited between October 2010 and January 2014. A subset of these patients was selected to measure Plasmodium falciparum clearance time. Polymerase chain reaction-corrected adequate clinical and parasitological responses were 100% for AS + SP and 98.2% for AL with no significant difference (P = 0.06). The reinfection rates were comparable (P = 0.63) with 8.0% for AS + SP and 12.6% for AL. Individuals under 8 years were more susceptible to treatment failure (relative risk = 1.9; 95% confidence interval = 1.2, 3.3). Median parasite clearance half-life was 1.7 hours (interquartile range [IQR] = 1.3-2.2) for AS + SP and 1.9 hours (IQR = 1.5 2.5) for AL with no statistically significant difference (P = 0.24). Efficacy of AS + SP and AL was high. This study provides baseline information on parasite clearance half-lives after ACT treatment, particularly AS + SP, in Mali. PMID- 26811432 TI - Measuring Socioeconomic Inequalities in Relation to Malaria Risk: A Comparison of Metrics in Rural Uganda. AB - Socioeconomic position (SEP) is an important risk factor for malaria, but there is no consensus on how to measure SEP in malaria studies. We evaluated the relative strength of four indicators of SEP in predicting malaria risk in Nagongera, Uganda. A total of 318 children resident in 100 households were followed for 36 months to measure parasite prevalence routinely every 3 months and malaria incidence by passive case detection. Household SEP was determined using: 1) two wealth indices, 2) income, 3) occupation, and 4) education. Wealth Index I (reference) included only asset ownership variables. Wealth Index II additionally included food security and house construction variables, which may directly affect malaria. In multivariate analysis, only Wealth Index II and income were associated with the human biting rate, only Wealth Indices I and II were associated with parasite prevalence, and only caregiver's education was associated with malaria incidence. This is the first evaluation of metrics beyond wealth and consumption indices for measuring the association between SEP and malaria. The wealth index still predicted malaria risk after excluding variables directly associated with malaria, but the strength of association was lower. In this setting, wealth indices, income, and education were stronger predictors of socioeconomic differences in malaria risk than occupation. PMID- 26811433 TI - Coxiella burnetii Infection in a Community Operating a Large-Scale Cow and Goat Dairy, Missouri, 2013. AB - Coxiella burnetii is a zoonotic pathogen that causes Q fever in humans and is transmitted primarily from infected goats, sheep, or cows. Q fever typically presents as an acute febrile illness; however, individuals with certain predisposing conditions, including cardiac valvulopathy, are at risk for chronic Q fever, a serious manifestation that may present as endocarditis. In response to a cluster of Q fever cases detected by public health surveillance, we evaluated C. burnetii infection in a community that operates a large-scale cow and goat dairy. A case was defined as an individual linked to the community with a C. burnetii phase II IgG titer >= 128. Of 135 participants, 47 (35%) cases were identified. Contact with or close proximity to cows, goats, and their excreta was associated with being a case (relative risk 2.7, 95% confidence interval 1.3 5.3). Cases were also identified among individuals without cow or goat contact and could be related to windborne spread or tracking of C. burnetii on fomites within the community. A history of injection drug use was reported by 26/130 (20%) participants; follow-up for the presence of valvulopathy and monitoring for development of chronic Q fever may be especially important among this population. PMID- 26811434 TI - Alternative to left ventricular lead implantation through the coronary sinus: 1 year experience with a minimally invasive and robotically guided approach. AB - AIMS: Left ventricular (LV) lead implantation through the coronary sinus (CS) can be limited and sometimes not possible-alternative approaches are needed. Minimally invasive, robotically guided LV lead implantation has major advantages, but there are little published data about the short- and long-term follow-ups, in terms of feasibility, safety, electrical performance, and impact on clinical outcome. METHODS AND RESULTS: A total of 21 heart failure patients underwent robotically guided LV lead implantation using the Da Vinci Robotic System. Indications were failed implant with conventional approach through the CS (n = 16) and non-response to conventional cardiac resynchronization therapy (n = 5). During the procedure, the entire LV free wall was exposed through 3 transthoracic ports (10 mm diameter each) allowing ample choice of stimulation site and the ability to implant 2 LV leads via a Y connector. Patients were prospectively followed up for 1 year. The two LV leads were successfully implanted in all patients. No peri-procedural complications were observed. After a mean stay in the intensive care unit of 1.2 +/- 4 days, the 21 patients were hospitalized in the EP department for 6.7 +/- 2.9 days. Acute LV thresholds were excellent (1.0 V +/- 0.6/0.4 ms) and stayed stable at 1-year follow-up (1.5 V +/- 0.6/0.4 ms, P = 0.21). Four patients demonstrated an increased threshold (>2 V/0.4 ms). There was no phrenic nerve stimulation. After 12 months, in the failed implant group, 69% of the patients were echocardiographic and clinical responders. CONCLUSION: The robotic approach was feasible, safe, and minimally invasive. Accordingly, robotically guided LV lead implantation seems to offer a new alternative when conventional approaches are not suitable. PMID- 26811435 TI - A qualitative analysis of women's explanations for changing contraception: the importance of non-contraceptive effects. AB - BACKGROUND: Women commonly report changing contraceptive methods because of side effects. However, there is a lack of literature that has thoroughly examined women's perspectives, including why they changed contraception. AIM: Using qualitative data from a contraceptive survey of young Australian women, we explored women's explanations for their recent changes in contraception. METHOD: A thematic analysis of 1051 responses to a question about why women recently changed contraception was conducted. RESULTS: Themes reflected reasons for changing contraception which included: both contraceptive and non-contraceptive (4%); relationship/sexual (9%); medical (11%); contraceptive (18%); non contraceptive (41%). A minority of responses were uncoded (17%). Non contraceptive effects (effects unrelated to pregnancy prevention) featured most frequently in women's reasons for changing contraception. CONCLUSIONS: While cessation of various contraceptives due to unwanted side-effects is a well-known phenomenon, this analysis provides evidence of the changing of contraception for its non-contraceptive effects and reframes the notion of 'side-effects'. PMID- 26811436 TI - Moral Heroes Look Up and to the Right. AB - Portraits of moral heroes often portray the hero gazing up and to the viewer's right in part because ideologically minded followers select and propagate these images of their leaders. Study 1 found that the gaze direction of portraits of moral heroes (e.g., Martin Luther King, Jr.) tend to show the hero looking up-and right more often than chance would predict, and more often than portraits of celebrities (e.g., Elvis Presley) do. In Studies 2 and 3, we asked participants to play the role of an ideologically motivated follower, and select an image of their leader to promote the cause. Participants preferentially selected the up and-right version. In Study 4, we found that conceptual metaphors linking directionality to personal virtues of warmth, pride, and future-mindedness helped explain why the up-and-right posture looks most heroic. Followers play an active role in advancing social causes by portraying their leaders as moral heroes. PMID- 26811437 TI - Halo Effects in Trait Assessment Depend on Information Valence: Why Being Honest Makes You Industrious, but Lying Does Not Make You Lazy. AB - We propose stronger halo effects in trait assessments from positive information relative to negative information. Due to positive information's higher similarity, positive information should foster both indirect (from a global impression to traits) and direct halo effects (from traits to traits). Negative information's relative distinctiveness should foster only direct halo effects, leading to weaker halo effects overall. Four experiments support these predictions using agency traits and communion traits and behaviors. Further supporting the predictions, halo effects from positive information were visible both within (i.e., from communion/agency information to communion/agency traits) and across (i.e., from agency/communion information to communion/agency traits) these fundamental dimensions of social perception. Halo effects from negative information were visible only within dimensions. The study thereby explains why halo effects from negative information are usually weaker; it supports different processes underlying halo effects; and it provides a case in person perception where positive information has more impact than negative information. PMID- 26811438 TI - Cost-effectiveness of the 'Walcheren Integrated Care Model' intervention for community-dwelling frail elderly. AB - BACKGROUND: An important aim of integrated care for frail elderly is to generate more cost-effective health care. However, empirical research on the cost effectiveness of integrated care for community-dwelling frail elderly is limited. OBJECTIVE: This study reports on the cost-effectiveness of the Walcheren Integrated Care Model (WICM) after 12 months from a societal perspective. METHODS: The design of this study was quasi-experimental. In total, 184 frail elderly patients from 3 GP practices that implemented the WICM were compared with 193 frail elderly patients of 5 GP practices that provided care as usual. Effects were determined by health-related quality of life (EQ-5D questionnaire). Costs were assessed based on questionnaires, GP files, time registrations and reports from multidisciplinary meetings. Average costs and effects were compared using t tests. The incremental cost-effectiveness ratio (ICER) was calculated, and bootstrap methods were used to determine its reliability. RESULTS: Neither the WICM nor care as usual resulted in a change in health-related quality of life. The average total costs of the WICM were higher than care as usual (17089 euros versus 15189 euros). The incremental effects were 0.00, whereas the incremental costs were 1970 euros, indicating an ICER of 412450 euros. CONCLUSIONS: The WICM is not cost-effective, and the costs per quality-adjusted life year are high. The costs of the integrated care intervention do not outweigh the limited effects on health-related quality of life after 12 months. More analyses of the cost effectiveness of integrated care for community-dwelling frail elderly are recommended as well as consideration of the specific costs and effects. PMID- 26811439 TI - Long-term outcome in dogs with chronic enteropathies: 203 cases. PMID- 26811440 TI - European molecular epidemiology and strain diversity of feline calicivirus. AB - Feline calicivirus (FCV) causes a variable syndrome of upper respiratory tract disease, mouth ulcers and lameness. A convenience-based prospective sample of oropharyngeal swabs (n=426) was obtained from five countries (France, Germany, Greece, Portugal and the UK). The prevalence of FCV by virus isolation was 22.2 per cent. Multivariable analysis found that animals presenting with lymphoplasmacytic gingivitis stomatitis complex were more likely to test positive for FCV infection. Furthermore, vaccinated cats up to 48 months of age were significantly less likely to be infected with FCV than unvaccinated animals of similar ages. Phylogenetic analysis based on consensus sequences for the immunodominant region of the capsid gene from 72 FCV isolates identified 46 strains. Thirteen of the 14 strains with more than one sequence were restricted to individual regions or sites in individual countries; the exception was a strain present in two sites close to each other in France. Four strains were present in more than one household. Five colonies, four of which were rescue shelters, had multiple strains within them. Polymerase sequence suggested possible rare recombination events. These locally, nationally and internationally diverse FCV populations maintain a continuous challenge to the control of FCV infection and disease. PMID- 26811441 TI - Recovery of chronically lame dairy cows following treatment for claw horn lesions: a randomised controlled trial. AB - A positively controlled, randomised controlled trial (RCT) was undertaken to test recovery of cows with claw horn lesions resulting in lameness of greater than two weeks duration. Cows on seven commercial farms were mobility scored fortnightly and selected by lameness severity and chronicity. Study cows all received a therapeutic trim then random allocation of: no further treatment (trim only (TRM)), plastic shoe (TS) or plastic shoe and NSAID (TSN). Recovery was assessed by mobility score at 42 (+/-4) days post treatment by an observer blind to treatment group. Multivariable analysis showed no significant effect of treatment with an almost identical, low response rate to treatment across all groups (Percentage non-lame at outcome: TRM--15 per cent, TS--15 per cent, TSN--16 per cent). When compared with results of a similar RCT on acutely lame cows, where response rates to treatment were substantially higher, it can be concluded that any delay in treatment is likely to reduce the rate of recovery, suggesting early identification and treatment is key. Thirty-eight per cent of animals treated in this study were lame on the contralateral limb at outcome suggesting that both hindlimbs should be examined and a preventive or if necessary a therapeutic foot trim performed when lameness is identified particularly if the duration of lameness is unknown. PMID- 26811442 TI - Megafauna and ecosystem function from the Pleistocene to the Anthropocene. AB - Large herbivores and carnivores (the megafauna) have been in a state of decline and extinction since the Late Pleistocene, both on land and more recently in the oceans. Much has been written on the timing and causes of these declines, but only recently has scientific attention focused on the consequences of these declines for ecosystem function. Here, we review progress in our understanding of how megafauna affect ecosystem physical and trophic structure, species composition, biogeochemistry, and climate, drawing on special features of PNAS and Ecography that have been published as a result of an international workshop on this topic held in Oxford in 2014. Insights emerging from this work have consequences for our understanding of changes in biosphere function since the Late Pleistocene and of the functioning of contemporary ecosystems, as well as offering a rationale and framework for scientifically informed restoration of megafaunal function where possible and appropriate. PMID- 26811443 TI - Genomic reconstruction of the history of extant populations of India reveals five distinct ancestral components and a complex structure. AB - India, occupying the center stage of Paleolithic and Neolithic migrations, has been underrepresented in genome-wide studies of variation. Systematic analysis of genome-wide data, using multiple robust statistical methods, on (i) 367 unrelated individuals drawn from 18 mainland and 2 island (Andaman and Nicobar Islands) populations selected to represent geographic, linguistic, and ethnic diversities, and (ii) individuals from populations represented in the Human Genome Diversity Panel (HGDP), reveal four major ancestries in mainland India. This contrasts with an earlier inference of two ancestries based on limited population sampling. A distinct ancestry of the populations of Andaman archipelago was identified and found to be coancestral to Oceanic populations. Analysis of ancestral haplotype blocks revealed that extant mainland populations (i) admixed widely irrespective of ancestry, although admixtures between populations was not always symmetric, and (ii) this practice was rapidly replaced by endogamy about 70 generations ago, among upper castes and Indo-European speakers predominantly. This estimated time coincides with the historical period of formulation and adoption of sociocultural norms restricting intermarriage in large social strata. A similar replacement observed among tribal populations was temporally less uniform. PMID- 26811444 TI - Three-dimensional manipulation of single cells using surface acoustic waves. AB - The ability of surface acoustic waves to trap and manipulate micrometer-scale particles and biological cells has led to many applications involving "acoustic tweezers" in biology, chemistry, engineering, and medicine. Here, we present 3D acoustic tweezers, which use surface acoustic waves to create 3D trapping nodes for the capture and manipulation of microparticles and cells along three mutually orthogonal axes. In this method, we use standing-wave phase shifts to move particles or cells in-plane, whereas the amplitude of acoustic vibrations is used to control particle motion along an orthogonal plane. We demonstrate, through controlled experiments guided by simulations, how acoustic vibrations result in micromanipulations in a microfluidic chamber by invoking physical principles that underlie the formation and regulation of complex, volumetric trapping nodes of particles and biological cells. We further show how 3D acoustic tweezers can be used to pick up, translate, and print single cells and cell assemblies to create 2D and 3D structures in a precise, noninvasive, label-free, and contact-free manner. PMID- 26811445 TI - Cryptochrome 2 mediates directional magnetoreception in cockroaches. AB - The ability to perceive geomagnetic fields (GMFs) represents a fascinating biological phenomenon. Studies on transgenic flies have provided evidence that photosensitive Cryptochromes (Cry) are involved in the response to magnetic fields (MFs). However, none of the studies tackled the problem of whether the Cry dependent magnetosensitivity is coupled to the sole MF presence or to the direction of MF vector. In this study, we used gene silencing and a directional MF to show that mammalian-like Cry2 is necessary for a genuine directional response to periodic rotations of the GMF vector in two insect species. Longer wavelengths of light required higher photon fluxes for a detectable behavioral response, and a sharp detection border was present in the cyan/green spectral region. Both observations are consistent with involvement of the FADox, FAD(*-) and FADH(-) redox forms of flavin. The response was lost upon covering the eyes, demonstrating that the signal is perceived in the eye region. Immunohistochemical staining detected Cry2 in the hemispherical layer of laminal glia cells underneath the retina. Together, these findings identified the eye-localized Cry2 as an indispensable component and a likely photoreceptor of the directional GMF response. Our study is thus a clear step forward in deciphering the in vivo effects of GMF and supports the interaction of underlying mechanism with the visual system. PMID- 26811446 TI - Molecular requirements for a pandemic influenza virus: An acid-stable hemagglutinin protein. AB - Influenza pandemics require that a virus containing a hemagglutinin (HA) surface antigen previously unseen by a majority of the population becomes airborne transmissible between humans. Although the HA protein is central to the emergence of a pandemic influenza virus, its required molecular properties for sustained transmission between humans are poorly defined. During virus entry, the HA protein binds receptors and is triggered by low pH in the endosome to cause membrane fusion; during egress, HA contributes to virus assembly and morphology. In 2009, a swine influenza virus (pH1N1) jumped to humans and spread globally. Here we link the pandemic potential of pH1N1 to its HA acid stability, or the pH at which this one-time-use nanomachine is either triggered to cause fusion or becomes inactivated in the absence of a target membrane. In surveillance isolates, our data show HA activation pH values decreased during the evolution of H1N1 from precursors in swine (pH 5.5-6.0), to early 2009 human cases (pH 5.5), and then to later human isolates (pH 5.2-5.4). A loss-of-function pH1N1 virus with a destabilizing HA1-Y17H mutation (pH 6.0) was less pathogenic in mice and ferrets, less transmissible by contact, and no longer airborne-transmissible. A ferret-adapted revertant (HA1-H17Y/HA2-R106K) regained airborne transmissibility by stabilizing HA to an activation pH of 5.3, similar to that of human-adapted isolates from late 2009-2014. Overall, these studies reveal that a stable HA (activation pH <= 5.5) is necessary for pH1N1 influenza virus pathogenicity and airborne transmissibility in ferrets and is associated with pandemic potential in humans. PMID- 26811447 TI - Songbirds use spectral shape, not pitch, for sound pattern recognition. AB - Humans easily recognize "transposed" musical melodies shifted up or down in log frequency. Surprisingly, songbirds seem to lack this capacity, although they can learn to recognize human melodies and use complex acoustic sequences for communication. Decades of research have led to the widespread belief that songbirds, unlike humans, are strongly biased to use absolute pitch (AP) in melody recognition. This work relies almost exclusively on acoustically simple stimuli that may belie sensitivities to more complex spectral features. Here, we investigate melody recognition in a species of songbird, the European Starling (Sturnus vulgaris), using tone sequences that vary in both pitch and timbre. We find that small manipulations altering either pitch or timbre independently can drive melody recognition to chance, suggesting that both percepts are poor descriptors of the perceptual cues used by birds for this task. Instead we show that melody recognition can generalize even in the absence of pitch, as long as the spectral shapes of the constituent tones are preserved. These results challenge conventional views regarding the use of pitch cues in nonhuman auditory sequence recognition. PMID- 26811448 TI - Genome-wide coexpression of steroid receptors in the mouse brain: Identifying signaling pathways and functionally coordinated regions. AB - Steroid receptors are pleiotropic transcription factors that coordinate adaptation to different physiological states. An important target organ is the brain, but even though their effects are well studied in specific regions, brain wide steroid receptor targets and mediators remain largely unknown due to the complexity of the brain. Here, we tested the idea that novel aspects of steroid action can be identified through spatial correlation of steroid receptors with genome-wide mRNA expression across different regions in the mouse brain. First, we observed significant coexpression of six nuclear receptors (NRs) [androgen receptor (Ar), estrogen receptor alpha (Esr1), estrogen receptor beta (Esr2), glucocorticoid receptor (Gr), mineralocorticoid receptor (Mr), and progesterone receptor (Pgr)] with sets of steroid target genes that were identified in single brain regions. These coexpression relationships were also present in distinct other brain regions, suggestive of as yet unidentified coordinate regulation of brain regions by, for example, glucocorticoids and estrogens. Second, coexpression of a set of 62 known NR coregulators and the six steroid receptors in 12 nonoverlapping mouse brain regions revealed selective downstream pathways, such as Pak6 as a mediator for the effects of Ar and Gr on dopaminergic transmission. Third, Magel2 and Irs4 were identified and validated as strongly responsive targets to the estrogen diethylstilbestrol in the mouse hypothalamus. The brain- and genome-wide correlations of mRNA expression levels of six steroid receptors that we provide constitute a rich resource for further predictions and understanding of brain modulation by steroid hormones. PMID- 26811450 TI - Correction for Ling et al., Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution. PMID- 26811449 TI - Observation of femtosecond X-ray interactions with matter using an X-ray-X-ray pump-probe scheme. AB - Resolution in the X-ray structure determination of noncrystalline samples has been limited to several tens of nanometers, because deep X-ray irradiation required for enhanced resolution causes radiation damage to samples. However, theoretical studies predict that the femtosecond (fs) durations of X-ray free electron laser (XFEL) pulses make it possible to record scattering signals before the initiation of X-ray damage processes; thus, an ultraintense X-ray beam can be used beyond the conventional limit of radiation dose. Here, we verify this scenario by directly observing femtosecond X-ray damage processes in diamond irradiated with extraordinarily intense (~10(19) W/cm(2)) XFEL pulses. An X-ray pump-probe diffraction scheme was developed in this study; tightly focused double 5-fs XFEL pulses with time separations ranging from sub-fs to 80 fs were used to excite (i.e., pump) the diamond and characterize (i.e., probe) the temporal changes of the crystalline structures through Bragg reflection. It was found that the pump and probe diffraction intensities remain almost constant for shorter time separations of the double pulse, whereas the probe diffraction intensities decreased after 20 fs following pump pulse irradiation due to the X-ray-induced atomic displacement. This result indicates that sub-10-fs XFEL pulses enable conductions of damageless structural determinations and supports the validity of the theoretical predictions of ultraintense X-ray-matter interactions. The X-ray pump-probe scheme demonstrated here would be effective for understanding ultraintense X-ray-matter interactions, which will greatly stimulate advanced XFEL applications, such as atomic structure determination of a single molecule and generation of exotic matters with high energy densities. PMID- 26811451 TI - Life history effects on the molecular clock of autosomes and sex chromosomes. AB - One of the foundational results in molecular evolution is that the rate at which neutral substitutions accumulate on a lineage equals the rate at which mutations arise. Traits that affect rates of mutation therefore also affect the phylogenetic "molecular clock." We consider the effects of sex-specific generation times and mutation rates in species with two sexes. In particular, we focus on the effects that the age of onset of male puberty and rates of spermatogenesis have likely had in hominids (great apes), considering a model that approximates features of the mutational process in mammals, birds, and some other vertebrates. As we show, this model can account for a number of seemingly disparate observations: notably, the puzzlingly low X-to-autosome ratios of substitution rates in humans and chimpanzees and differences in rates of autosomal substitutions among hominine lineages (i.e., humans, chimpanzees, and gorillas). The model further suggests how to translate pedigree-based estimates of human mutation rates into split times among extant hominoids (apes), given sex specific life histories. In so doing, it largely bridges the gap reported between estimates of split times based on fossil and molecular evidence, in particular suggesting that the human-chimpanzee split may have occurred as recently as 6.6 Mya. The model also implies that the "generation time effect" should be stronger in short-lived species, explaining why the generation time has a major influence on yearly substitution rates in mammals but only a subtle one in human pedigrees. PMID- 26811452 TI - Successful immunotherapy induces previously unidentified allergen-specific CD4+ T cell subsets. AB - Allergen immunotherapy can desensitize even subjects with potentially lethal allergies, but the changes induced in T cells that underpin successful immunotherapy remain poorly understood. In a cohort of peanut-allergic participants, we used allergen-specific T-cell sorting and single-cell gene expression to trace the transcriptional "roadmap" of individual CD4+ T cells throughout immunotherapy. We found that successful immunotherapy induces allergen specific CD4+ T cells to expand and shift toward an "anergic" Th2 T-cell phenotype largely absent in both pretreatment participants and healthy controls. These findings show that sustained success, even after immunotherapy is withdrawn, is associated with the induction, expansion, and maintenance of immunotherapy-specific memory and naive T-cell phenotypes as early as 3 mo into immunotherapy. These results suggest an approach for immune monitoring participants undergoing immunotherapy to predict the success of future treatment and could have implications for immunotherapy targets in other diseases like cancer, autoimmune disease, and transplantation. PMID- 26811454 TI - Profile of Benjamin Cravatt. PMID- 26811455 TI - Dispersal limitation induces long-term biomass collapse in overhunted Amazonian forests. AB - Tropical forests are the global cornerstone of biological diversity, and store 55% of the forest carbon stock globally, yet sustained provisioning of these forest ecosystem services may be threatened by hunting-induced extinctions of plant-animal mutualisms that maintain long-term forest dynamics. Large-bodied Atelinae primates and tapirs in particular offer nonredundant seed-dispersal services for many large-seeded Neotropical tree species, which on average have higher wood density than smaller-seeded and wind-dispersed trees. We used field data and models to project the spatial impact of hunting on large primates by ~ 1 million rural households throughout the Brazilian Amazon. We then used a unique baseline dataset on 2,345 1-ha tree plots arrayed across the Brazilian Amazon to model changes in aboveground forest biomass under different scenarios of hunting induced large-bodied frugivore extirpation. We project that defaunation of the most harvest-sensitive species will lead to losses in aboveground biomass of between 2.5-5.8% on average, with some losses as high as 26.5-37.8%. These findings highlight an urgent need to manage the sustainability of game hunting in both protected and unprotected tropical forests, and place full biodiversity integrity, including populations of large frugivorous vertebrates, firmly in the agenda of reducing emissions from deforestation and forest degradation (REDD+) programs. PMID- 26811453 TI - Proinflammatory signal suppresses proliferation and shifts macrophage metabolism from Myc-dependent to HIF1alpha-dependent. AB - As a phenotypically plastic cellular population, macrophages change their physiology in response to environmental signals. Emerging evidence suggests that macrophages are capable of tightly coordinating their metabolic programs to adjust their immunological and bioenergetic functional properties, as needed. Upon mitogenic stimulation, quiescent macrophages enter the cell cycle, increasing their bioenergetic and biosynthetic activity to meet the demands of cell growth. Proinflammatory stimulation, however, suppresses cell proliferation, while maintaining a heightened metabolic activity imposed by the production of bactericidal factors. Here, we report that the mitogenic stimulus, colony stimulating factor 1 (CSF-1), engages a myelocytomatosis viral oncogen (Myc) dependent transcriptional program that is responsible for cell cycle entry and the up-regulation of glucose and glutamine catabolism in bone marrow-derived macrophages (BMDMs). However, the proinflammatory stimulus, lipopolysaccharide (LPS), suppresses Myc expression and cell proliferation and engages a hypoxia inducible factor alpha (HIF1alpha)-dependent transcriptional program that is responsible for heightened glycolysis. The acute deletion of Myc or HIF1alpha selectively impaired the CSF-1- or LPS-driven metabolic activities in BMDM, respectively. Finally, inhibition of glycolysis by 2-deoxyglucose (2-DG) or genetic deletion of HIF1alpha suppressed LPS-induced inflammation in vivo. Our studies indicate that a switch from a Myc-dependent to a HIF1alpha-dependent transcriptional program may regulate the robust bioenergetic support for an inflammatory response, while sparing Myc-dependent proliferation. PMID- 26811456 TI - Obeticholic acid, a synthetic bile acid agonist of the farnesoid X receptor, attenuates experimental autoimmune encephalomyelitis. AB - Bile acids are ligands for the nuclear hormone receptor, farnesoid X receptor (FXR). The bile acid-FXR interaction regulates bile acid synthesis, transport, and cholesterol metabolism. Recently, bile acid-FXR regulation has been reported to play an integral role in both hepatic and intestinal inflammation, and in atherosclerosis. In this study, we found that FXR knockout mice had more disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Obeticholic acid (6alpha-ethyl-chenodeoxycholic acid, 6 ECDCA), a synthetic FXR agonist, is an orally available drug that is currently in clinical trials for the treatment of inflammatory diseases such as alcoholic hepatitis, nonalcoholic steatohepatitis, and primary biliary cirrhosis. When we treated mice exhibiting established EAE with 6-ECDCA, or the natural FXR ligand chenodeoxycholic acid (CDCA), clinical disease was ameliorated by (i) suppressing lymphocyte activation and proinflammatory cytokine production; (ii) reducing CD4(+) T cells and CD19(+) B cell populations and their expression of negative checkpoint regulators programmed cell death protein 1 (PD1), programmed death ligand 1 (PD-L1), and B and T lymphocyte attenuator (BTLA); (iii) increasing CD8(+) T cells and PD1, PDl-1, and BTLA expression; and (iv) reducing VLA-4 expression in both the T- and B-cell populations. Moreover, adoptive transfer of 6-ECDCA- or CDCA-treated donor cells failed to transfer disease in naive recipients. Thus, we show that FXR functions as a negative regulator in neuroinflammation and we highlight that FXR agonists represent a potential previously unidentified therapy for MS. PMID- 26811457 TI - Augmented efficacy of brentuximab vedotin combined with ruxolitinib and/or Navitoclax in a murine model of human Hodgkin's lymphoma. AB - Despite relative success of therapy for Hodgkin's lymphoma (HL), novel therapeutic agents are needed for patients with refractory or relapsed disease. Recently, anti-PD1 immunotherapy or treatment with the anti-CD30 toxin conjugate brentuximab vedotin (BV) have been associated with remissions; however, the median responses of complete responses (CRs) with the latter were only 6.7 mo. To obtain curative therapy, other effective agents, based on HL biology, would have to be given in combination with BV. Hodgkin's Reed-Sternberg (HRS) cells secrete cytokines including IL-6 and -13, leading to constitutive activation of JAK/STAT signaling. In the present study the JAK1/2 inhibitor ruxolitinib reduced phosphorylation of STAT3 and STAT6 and expression of c-Myc in the HL cell line HDLM-2. These changes were enhanced when, on the basis of a matrix screen of drug combinations, ruxolitinib was combined with the Bcl-2/Bcl-xL inhibitor Navitoclax. The combination augmented expression of Bik, Puma, and Bax, and attenuated Bcl-xL expression and the phosphorylation of Bad. The use of the two agent combination of either ruxolitinib or Navitoclax with BV or the three-agent combination strongly activated Bax and increased activities of cytochrome c and caspase-9 and -3 that, in turn, led to cleavage of poly(ADP ribose) polymerase and Mcl-1. Either ruxolitinib combined with Navitoclax or BV alone prolonged survival but did not cure HDLM-2 tumor-bearing mice, whereas BV combined with ruxolitinib and/or with Navitoclax resulted in a sustained, complete elimination of the HDLM-2 HL. These studies provide scientific support for a clinical trial to evaluate BV combined with ruxolitinib in select patients with HL. PMID- 26811458 TI - Clusters of polyhedra in spherical confinement. AB - Dense particle packing in a confining volume remains a rich, largely unexplored problem, despite applications in blood clotting, plasmonics, industrial packaging and transport, colloidal molecule design, and information storage. Here, we report densest found clusters of the Platonic solids in spherical confinement, for up to [Formula: see text] constituent polyhedral particles. We examine the interplay between anisotropic particle shape and isotropic 3D confinement. Densest clusters exhibit a wide variety of symmetry point groups and form in up to three layers at higher N. For many N values, icosahedra and dodecahedra form clusters that resemble sphere clusters. These common structures are layers of optimal spherical codes in most cases, a surprising fact given the significant faceting of the icosahedron and dodecahedron. We also investigate cluster density as a function of N for each particle shape. We find that, in contrast to what happens in bulk, polyhedra often pack less densely than spheres. We also find especially dense clusters at so-called magic numbers of constituent particles. Our results showcase the structural diversity and experimental utility of families of solutions to the packing in confinement problem. PMID- 26811459 TI - Native American depopulation, reforestation, and fire regimes in the Southwest United States, 1492-1900 CE. AB - Native American populations declined between 1492 and 1900 CE, instigated by the European colonization of the Americas. However, the magnitude, tempo, and ecological effects of this depopulation remain the source of enduring debates. Recently, scholars have linked indigenous demographic decline, Neotropical reforestation, and shifting fire regimes to global changes in climate, atmosphere, and the Early Anthropocene hypothesis. In light of these studies, we assess these processes in conifer-dominated forests of the Southwest United States. We compare light detection and ranging data, archaeology, dendrochronology, and historical records from the Jemez Province of New Mexico to quantify population losses, establish dates of depopulation events, and determine the extent and timing of forest regrowth and fire regimes between 1492 and 1900. We present a new formula for the estimation of Pueblo population based on architectural remains and apply this formula to 18 archaeological sites in the Jemez Province. A dendrochronological study of remnant wood establishes dates of terminal occupation at these sites. By combining our results with historical records, we report a model of pre- and post-Columbian population dynamics in the Jemez Province. Our results indicate that the indigenous population of the Jemez Province declined by 87% following European colonization but that this reduction occurred nearly a century after initial contact. Depopulation also triggered an increase in the frequency of extensive surface fires between 1640 and 1900. Ultimately, this study illustrates the quality of integrated archaeological and paleoecological data needed to assess the links between Native American population decline and ecological change after European contact. PMID- 26811461 TI - Correction to Supporting Information for Rosenzweig et al., Assessing agricultural risks of climate change in the 21st century in a global gridded crop model intercomparison. PMID- 26811460 TI - Biogeography of a human oral microbiome at the micron scale. AB - The spatial organization of complex natural microbiomes is critical to understanding the interactions of the individual taxa that comprise a community. Although the revolution in DNA sequencing has provided an abundance of genomic level information, the biogeography of microbiomes is almost entirely uncharted at the micron scale. Using spectral imaging fluorescence in situ hybridization as guided by metagenomic sequence analysis, we have discovered a distinctive, multigenus consortium in the microbiome of supragingival dental plaque. The consortium consists of a radially arranged, nine-taxon structure organized around cells of filamentous corynebacteria. The consortium ranges in size from a few tens to a few hundreds of microns in radius and is spatially differentiated. Within the structure, individual taxa are localized at the micron scale in ways suggestive of their functional niche in the consortium. For example, anaerobic taxa tend to be in the interior, whereas facultative or obligate aerobes tend to be at the periphery of the consortium. Consumers and producers of certain metabolites, such as lactate, tend to be near each other. Based on our observations and the literature, we propose a model for plaque microbiome development and maintenance consistent with known metabolic, adherence, and environmental considerations. The consortium illustrates how complex structural organization can emerge from the micron-scale interactions of its constituent organisms. The understanding that plaque community organization is an emergent phenomenon offers a perspective that is general in nature and applicable to other microbiomes. PMID- 26811462 TI - Near-linear response of mean monsoon strength to a broad range of radiative forcings. AB - Theoretical models have been used to argue that seasonal mean monsoons will shift abruptly and discontinuously from wet to dry stable states as their radiative forcings pass a critical threshold, sometimes referred to as a "tipping point." Further support for a strongly nonlinear response of monsoons to radiative forcings is found in the seasonal onset of the South Asian summer monsoon, which is abrupt compared with the annual cycle of insolation. Here it is shown that the seasonal mean strength of monsoons instead exhibits a nearly linear dependence on a wide range of radiative forcings. First, a previous theory that predicted a discontinuous, threshold response is shown to omit a dominant stabilizing term in the equations of motion; a corrected theory predicts a continuous and nearly linear response of seasonal mean monsoon strength to forcings. A comprehensive global climate model is then used to show that the seasonal mean South Asian monsoon exhibits a near-linear dependence on a wide range of isolated greenhouse gas, aerosol, and surface albedo forcings. This model reproduces the observed abrupt seasonal onset of the South Asian monsoon but produces a near-linear response of the mean monsoon by changing the duration of the summer circulation and the latitude of that circulation's ascent branch. Thus, neither a physically correct theoretical model nor a comprehensive climate model support the idea that seasonal mean monsoons will undergo abrupt, nonlinear shifts in response to changes in greenhouse gas concentrations, aerosol emissions, or land surface albedo. PMID- 26811463 TI - Dysbiosis-induced IL-33 contributes to impaired antiviral immunity in the genital mucosa. AB - Commensal microbiota are well known to play an important role in antiviral immunity by providing immune inductive signals; however, the consequence of dysbiosis on antiviral immunity remains unclear. We demonstrate that dysbiosis caused by oral antibiotic treatment directly impairs antiviral immunity following viral infection of the vaginal mucosa. Antibiotic-treated mice succumbed to mucosal herpes simplex virus type 2 infection more rapidly than water-fed mice, and also showed delayed viral clearance at the site of infection. However, innate immune responses, including type I IFN and proinflammatory cytokine production at infection sites, as well as induction of virus-specific CD4 and CD8 T-cell responses in draining lymph nodes, were not impaired in antibiotic-treated mice. By screening the factors controlling antiviral immunity, we found that IL-33, an alarmin released in response to tissue damage, was secreted from vaginal epithelium after the depletion of commensal microbiota. This cytokine suppresses local antiviral immunity by blocking the migration of effector T cells to the vaginal tissue, thereby inhibiting the production of IFN-gamma, a critical cytokine for antiviral defense, at local infection sites. These findings provide insight into the mechanisms of homeostasis maintained by commensal bacteria, and reveal a deleterious consequence of dysbiosis in antiviral immune defense. PMID- 26811464 TI - Calcium can mobilize and activate myosin-VI. AB - The ability to coordinate the timing of motor protein activation lies at the center of a wide range of cellular motile processes including endocytosis, cell division, and cancer cell migration. We show that calcium dramatically alters the conformation and activity of the myosin-VI motor implicated in pivotal steps of these processes. We resolved the change in motor conformation and in structural flexibility using single particle analysis of electron microscopic data and identified interacting domains using fluorescence spectroscopy. We discovered that calcium binding to calmodulin increases the binding affinity by a factor of 2,500 for a bipartite binding site on myosin-VI. The ability of calcium calmodulin to seek out and bridge between binding site components directs a major rearrangement of the motor from a compact dormant state into a cargo binding primed state that is nonmotile. The lack of motility at high calcium is due to calmodulin switching to a higher affinity binding site, which leaves the original IQ-motif exposed, thereby destabilizing the lever arm. The return to low calcium can either restabilize the lever arm, required for translocating the cargo-bound motors toward the center of the cell, or refold the cargo-free motors into an inactive state ready for the next cellular calcium flux. PMID- 26811465 TI - Highly functionalized organic nitrates in the southeast United States: Contribution to secondary organic aerosol and reactive nitrogen budgets. AB - Speciated particle-phase organic nitrates (pONs) were quantified using online chemical ionization MS during June and July of 2013 in rural Alabama as part of the Southern Oxidant and Aerosol Study. A large fraction of pONs is highly functionalized, possessing between six and eight oxygen atoms within each carbon number group, and is not the common first generation alkyl nitrates previously reported. Using calibrations for isoprene hydroxynitrates and the measured molecular compositions, we estimate that pONs account for 3% and 8% of total submicrometer organic aerosol mass, on average, during the day and night, respectively. Each of the isoprene- and monoterpenes-derived groups exhibited a strong diel trend consistent with the emission patterns of likely biogenic hydrocarbon precursors. An observationally constrained diel box model can replicate the observed pON assuming that pONs (i) are produced in the gas phase and rapidly establish gas-particle equilibrium and (ii) have a short particle phase lifetime (~2-4 h). Such dynamic behavior has significant implications for the production and phase partitioning of pONs, organic aerosol mass, and reactive nitrogen speciation in a forested environment. PMID- 26811466 TI - Self-dispersed crumpled graphene balls in oil for friction and wear reduction. AB - Ultrafine particles are often used as lubricant additives because they are capable of entering tribological contacts to reduce friction and protect surfaces from wear. They tend to be more stable than molecular additives under high thermal and mechanical stresses during rubbing. It is highly desirable for these particles to remain well dispersed in oil without relying on molecular ligands. Borrowing from the analogy that pieces of paper that are crumpled do not readily stick to each other (unlike flat sheets), we expect that ultrafine particles resembling miniaturized crumpled paper balls should self-disperse in oil and could act like nanoscale ball bearings to reduce friction and wear. Here we report the use of crumpled graphene balls as a high-performance additive that can significantly improve the lubrication properties of polyalphaolefin base oil. The tribological performance of crumpled graphene balls is only weakly dependent on their concentration in oil and readily exceeds that of other carbon additives such as graphite, reduced graphene oxide, and carbon black. Notably, polyalphaolefin base oil with only 0.01-0.1 wt % of crumpled graphene balls outperforms a fully formulated commercial lubricant in terms of friction and wear reduction. PMID- 26811467 TI - Ocean-wide tracking of pelagic sharks reveals extent of overlap with longline fishing hotspots. AB - Overfishing is arguably the greatest ecological threat facing the oceans, yet catches of many highly migratory fishes including oceanic sharks remain largely unregulated with poor monitoring and data reporting. Oceanic shark conservation is hampered by basic knowledge gaps about where sharks aggregate across population ranges and precisely where they overlap with fishers. Using satellite tracking data from six shark species across the North Atlantic, we show that pelagic sharks occupy predictable habitat hotspots of high space use. Movement modeling showed sharks preferred habitats characterized by strong sea surface temperature gradients (fronts) over other available habitats. However, simultaneous Global Positioning System (GPS) tracking of the entire Spanish and Portuguese longline-vessel fishing fleets show an 80% overlap of fished areas with hotspots, potentially increasing shark susceptibility to fishing exploitation. Regions of high overlap between oceanic tagged sharks and longliners included the North Atlantic Current/Labrador Current convergence zone and the Mid-Atlantic Ridge southwest of the Azores. In these main regions, and subareas within them, shark/vessel co-occurrence was spatially and temporally persistent between years, highlighting how broadly the fishing exploitation efficiently "tracks" oceanic sharks within their space-use hotspots year-round. Given this intense focus of longliners on shark hotspots, our study argues the need for international catch limits for pelagic sharks and identifies a future role of combining fine-scale fish and vessel telemetry to inform the ocean-scale management of fisheries. PMID- 26811468 TI - Profile of Lawrence Steinman. PMID- 26811469 TI - Revisiting the contemporary sea-level budget on global and regional scales. AB - Dividing the sea-level budget into contributions from ice sheets and glaciers, the water cycle, steric expansion, and crustal movement is challenging, especially on regional scales. Here, Gravity Recovery And Climate Experiment (GRACE) gravity observations and sea-level anomalies from altimetry are used in a joint inversion, ensuring a consistent decomposition of the global and regional sea-level rise budget. Over the years 2002-2014, we find a global mean steric trend of 1.38 +/- 0.16 mm/y, compared with a total trend of 2.74 +/- 0.58 mm/y. This is significantly larger than steric trends derived from in situ temperature/salinity profiles and models which range from 0.66 +/- 0.2 to 0.94 +/ 0.1 mm/y. Mass contributions from ice sheets and glaciers (1.37 +/- 0.09 mm/y, accelerating with 0.03 +/- 0.02 mm/y(2)) are offset by a negative hydrological component (-0.29 +/- 0.26 mm/y). The combined mass rate (1.08 +/- 0.3 mm/y) is smaller than previous GRACE estimates (up to 2 mm/y), but it is consistent with the sum of individual contributions (ice sheets, glaciers, and hydrology) found in literature. The altimetric sea-level budget is closed by coestimating a remaining component of 0.22 +/- 0.26 mm/y. Well above average sea-level rise is found regionally near the Philippines (14.7 +/- 4.39 mm/y) and Indonesia (8.3 +/- 4.7 mm/y) which is dominated by steric components (11.2 +/- 3.58 mm/y and 6.4 +/- 3.18 mm/y, respectively). In contrast, in the central and Eastern part of the Pacific, negative steric trends (down to -2.8 +/- 1.53 mm/y) are detected. Significant regional components are found, up to 5.3 +/- 2.6 mm/y in the northwest Atlantic, which are likely due to ocean bottom pressure variations. PMID- 26811470 TI - Brain size predicts problem-solving ability in mammalian carnivores. AB - Despite considerable interest in the forces shaping the relationship between brain size and cognitive abilities, it remains controversial whether larger brained animals are, indeed, better problem-solvers. Recently, several comparative studies have revealed correlations between brain size and traits thought to require advanced cognitive abilities, such as innovation, behavioral flexibility, invasion success, and self-control. However, the general assumption that animals with larger brains have superior cognitive abilities has been heavily criticized, primarily because of the lack of experimental support for it. Here, we designed an experiment to inquire whether specific neuroanatomical or socioecological measures predict success at solving a novel technical problem among species in the mammalian order Carnivora. We presented puzzle boxes, baited with food and scaled to accommodate body size, to members of 39 carnivore species from nine families housed in multiple North American zoos. We found that species with larger brains relative to their body mass were more successful at opening the boxes. In a subset of species, we also used virtual brain endocasts to measure volumes of four gross brain regions and show that some of these regions improve model prediction of success at opening the boxes when included with total brain size and body mass. Socioecological variables, including measures of social complexity and manual dexterity, failed to predict success at opening the boxes. Our results, thus, fail to support the social brain hypothesis but provide important empirical support for the relationship between relative brain size and the ability to solve this novel technical problem. PMID- 26811471 TI - Greenhouse-icehouse transition in the Late Ordovician marks a step change in extinction regime in the marine plankton. AB - Two distinct regimes of extinction dynamic are present in the major marine zooplankton group, the graptolites, during the Ordovician and Silurian periods (486-418 Ma). In conditions of "background" extinction, which dominated in the Ordovician, taxonomic evolutionary rates were relatively low and the probability of extinction was highest among newly evolved species ("background extinction mode"). A sharp change in extinction regime in the Late Ordovician marked the onset of repeated severe spikes in the extinction rate curve; evolutionary turnover increased greatly in the Silurian, and the extinction mode changed to include extinction that was independent of species age ("high-extinction mode"). This change coincides with a change in global climate, from greenhouse to icehouse conditions. During the most extreme episode of extinction, the Late Ordovician Mass Extinction, old species were selectively removed ("mass extinction mode"). Our analysis indicates that selective regimes in the Paleozoic ocean plankton switched rapidly (generally in <0.5 My) from one mode to another in response to environmental change, even when restoration of the full ecosystem was much slower (several million years). The patterns observed are not a simple consequence of geographic range effects or of taxonomic changes from Ordovician to Silurian. Our results suggest that the dominant primary controls on extinction throughout the lifespan of this clade were abiotic (environmental), probably mediated by the microphytoplankton. PMID- 26811472 TI - Control of APC/C-dependent ubiquitin chain elongation by reversible phosphorylation. AB - Most metazoan E3 ligases contain a signature RING domain that promotes the transfer of ubiquitin from the active site of E2 conjugating enzymes to lysine residues in substrates. Although these RING-E3s depend on E2 enzymes for catalysis, how they turn on their E2s at the right time and place remains poorly understood. Here we report a phosphorylation-dependent mechanism that ensures timely activation of the E2 Ube2S by its RING-E3, the anaphase-promoting complex (APC/C); while phosphorylation of a specific serine residue in the APC/C coactivator Cdc20 prevents delivery of Ube2S to the APC/C, removal of this mark by PP2A(B56) allows Ube2S to bind the APC/C and catalyze ubiquitin chain elongation. PP2A(B56) also stabilizes kinetochore-microtubule attachments to shut off the spindle checkpoint, suggesting that cells regulate the E2-E3 interplay to coordinate ubiquitination with critical events during cell division. PMID- 26811473 TI - Polarized light modulates light-dependent magnetic compass orientation in birds. AB - Magnetoreception of the light-dependent magnetic compass in birds is suggested to be mediated by a radical-pair mechanism taking place in the avian retina. Biophysical models on magnetic field effects on radical pairs generally assume that the light activating the magnetoreceptor molecules is nondirectional and unpolarized, and that light absorption is isotropic. However, natural skylight enters the avian retina unidirectionally, through the cornea and the lens, and is often partially polarized. In addition, cryptochromes, the putative magnetoreceptor molecules, absorb light anisotropically, i.e., they preferentially absorb light of a specific direction and polarization, implying that the light-dependent magnetic compass is intrinsically polarization sensitive. To test putative interactions between the avian magnetic compass and polarized light, we developed a spatial orientation assay and trained zebra finches to magnetic and/or overhead polarized light cues in a four-arm "plus" maze. The birds did not use overhead polarized light near the zenith for sky compass orientation. Instead, overhead polarized light modulated light-dependent magnetic compass orientation, i.e., how the birds perceive the magnetic field. Birds were well oriented when tested with the polarized light axis aligned parallel to the magnetic field. When the polarized light axis was aligned perpendicular to the magnetic field, the birds became disoriented. These findings are the first behavioral evidence to our knowledge for a direct interaction between polarized light and the light-dependent magnetic compass in an animal. They reveal a fundamentally new property of the radical pair-based magnetoreceptor with key implications for how birds and other animals perceive the Earth's magnetic field. PMID- 26811474 TI - Biologic-free mechanically induced muscle regeneration. AB - Severe skeletal muscle injuries are common and can lead to extensive fibrosis, scarring, and loss of function. Clinically, no therapeutic intervention exists that allows for a full functional restoration. As a result, both drug and cellular therapies are being widely investigated for treatment of muscle injury. Because muscle is known to respond to mechanical loading, we investigated instead whether a material system capable of massage-like compressions could promote regeneration. Magnetic actuation of biphasic ferrogel scaffolds implanted at the site of muscle injury resulted in uniform cyclic compressions that led to reduced fibrous capsule formation around the implant, as well as reduced fibrosis and inflammation in the injured muscle. In contrast, no significant effect of ferrogel actuation on muscle vascularization or perfusion was found. Strikingly, ferrogel-driven mechanical compressions led to enhanced muscle regeneration and a ~threefold increase in maximum contractile force of the treated muscle at 2 wk compared with no-treatment controls. Although this study focuses on the repair of severely injured skeletal muscle, magnetically stimulated bioagent-free ferrogels may find broad utility in the field of regenerative medicine. PMID- 26811475 TI - Human neural crest cells contribute to coat pigmentation in interspecies chimeras after in utero injection into mouse embryos. AB - The neural crest (NC) represents multipotent cells that arise at the interphase between ectoderm and prospective epidermis of the neurulating embryo. The NC has major clinical relevance because it is involved in both inherited and acquired developmental abnormalities. The aim of this study was to establish an experimental platform that would allow for the integration of human NC cells (hNCCs) into the gastrulating mouse embryo. NCCs were derived from pluripotent mouse, rat, and human cells and microinjected into embryonic-day-8.5 embryos. To facilitate integration of the NCCs, we used recipient embryos that carried a c Kit mutation (W(sh)/W(sh)), which leads to a loss of melanoblasts and thus eliminates competition from the endogenous host cells. The donor NCCs migrated along the dorsolateral migration routes in the recipient embryos. Postnatal mice derived from injected embryos displayed pigmented hair, demonstrating differentiation of the NCCs into functional melanocytes. Although the contribution of human cells to pigmentation in the host was lower than that of mouse or rat donor cells, our results indicate that hNCCs, injected in utero, can integrate into the embryo and form mature functional cells in the animal. This mouse-human chimeric platform allows for a new approach to study NC development and diseases. PMID- 26811476 TI - A structured interdomain linker directs self-polymerization of human uromodulin. AB - Uromodulin (UMOD)/Tamm-Horsfall protein, the most abundant human urinary protein, plays a key role in chronic kidney diseases and is a promising therapeutic target for hypertension. Via its bipartite zona pellucida module (ZP-N/ZP-C), UMOD forms extracellular filaments that regulate kidney electrolyte balance and innate immunity, as well as protect against renal stones. Moreover, salt-dependent aggregation of UMOD filaments in the urine generates a soluble molecular net that captures uropathogenic bacteria and facilitates their clearance. Despite the functional importance of its homopolymers, no structural information is available on UMOD and how it self-assembles into filaments. Here, we report the crystal structures of polymerization regions of human UMOD and mouse ZP2, an essential sperm receptor protein that is structurally related to UMOD but forms heteropolymers. The structure of UMOD reveals that an extensive hydrophobic interface mediates ZP-N domain homodimerization. This arrangement is required for filament formation and is directed by an ordered ZP-N/ZP-C linker that is not observed in ZP2 but is conserved in the sequence of deafness/Crohn's disease associated homopolymeric glycoproteins alpha-tectorin (TECTA) and glycoprotein 2 (GP2). Our data provide an example of how interdomain linker plasticity can modulate the function of structurally similar multidomain proteins. Moreover, the architecture of UMOD rationalizes numerous pathogenic mutations in both UMOD and TECTA genes. PMID- 26811477 TI - Usp12 stabilizes the T-cell receptor complex at the cell surface during signaling. AB - Posttranslational modifications are central to the spatial and temporal regulation of protein function. Among others, phosphorylation and ubiquitylation are known to regulate proximal T-cell receptor (TCR) signaling. Here we used a systematic and unbiased approach to uncover deubiquitylating enzymes (DUBs) that participate during TCR signaling in primary mouse T lymphocytes. Using a C terminally modified vinyl methyl ester variant of ubiquitin (HA-Ub-VME), we captured DUBs that are differentially recruited to the cytosol on TCR activation. We identified ubiquitin-specific peptidase (Usp) 12 and Usp46, which had not been previously described in this pathway. Stimulation with anti-CD3 resulted in phosphorylation and time-dependent translocation of Usp12 from the nucleus to the cytosol. Usp12(-/-) Jurkat cells displayed defective NFkappaB, NFAT, and MAPK activities owing to attenuated surface expression of TCR, which were rescued on reconstitution of wild type Usp12. Proximity-based labeling with BirA-Usp12 revealed several TCR adaptor proteins acting as interactors in stimulated cells, of which LAT and Trat1 displayed reduced expression in Usp12(-/-) cells. We demonstrate that Usp12 deubiquitylates and prevents lysosomal degradation of LAT and Trat1 to maintain the proximal TCR complex for the duration of signaling. Our approach benefits from the use of activity-based probes in primary cells without any previous genome modification, and underscores the importance of ubiquitin mediated regulation to refine signaling cascades. PMID- 26811479 TI - Nicastrin guards Alzheimer's gate. PMID- 26811478 TI - Transketolase counteracts oxidative stress to drive cancer development. AB - Cancer cells experience an increase in oxidative stress. The pentose phosphate pathway (PPP) is a major biochemical pathway that generates antioxidant NADPH. Here, we show that transketolase (TKT), an enzyme in the PPP, is required for cancer growth because of its ability to affect the production of NAPDH to counteract oxidative stress. We show that TKT expression is tightly regulated by the Nuclear Factor, Erythroid 2-Like 2 (NRF2)/Kelch-Like ECH-Associated Protein 1 (KEAP1)/BTB and CNC Homolog 1 (BACH1) oxidative stress sensor pathway in cancers. Disturbing the redox homeostasis of cancer cells by genetic knockdown or pharmacologic inhibition of TKT sensitizes cancer cells to existing targeted therapy (Sorafenib). Our study strengthens the notion that antioxidants are beneficial to cancer growth and highlights the therapeutic benefits of targeting pathways that generate antioxidants. PMID- 26811481 TI - George Hess: A scientific appreciation. PMID- 26811480 TI - Cytoplasmic isoforms of Kaposi sarcoma herpesvirus LANA recruit and antagonize the innate immune DNA sensor cGAS. AB - The latency-associated nuclear antigen (LANA) of Kaposi sarcoma herpesvirus (KSHV) is mainly localized and functions in the nucleus of latently infected cells, playing a pivotal role in the replication and maintenance of latent viral episomal DNA. In addition, N-terminally truncated cytoplasmic isoforms of LANA, resulting from internal translation initiation, have been reported, but their function is unknown. Using coimmunoprecipitation and MS, we found the cGMP-AMP synthase (cGAS), an innate immune DNA sensor, to be a cellular interaction partner of cytoplasmic LANA isoforms. By directly binding to cGAS, LANA, and particularly, a cytoplasmic isoform, inhibit the cGAS-STING-dependent phosphorylation of TBK1 and IRF3 and thereby antagonize the cGAS-mediated restriction of KSHV lytic replication. We hypothesize that cytoplasmic forms of LANA, whose expression increases during lytic replication, inhibit cGAS to promote the reactivation of the KSHV from latency. This observation points to a novel function of the cytoplasmic isoforms of LANA during lytic replication and extends the function of LANA from its role during latency to the lytic replication cycle. PMID- 26811482 TI - Challenges for determining the causal effects between social behavior and testosterone. PMID- 26811483 TI - Reply to Lane and Martin: Mitochondria do not boost the bioenergetic capacity of eukaryotic cells. PMID- 26811484 TI - Mitochondria, complexity, and evolutionary deficit spending. PMID- 26811485 TI - Reply to Fernandez-Marrero et al.: Role of BOK at the intersection of endoplasmic reticulum stress and apoptosis regulation. PMID- 26811486 TI - Contextualising consent. PMID- 26811487 TI - Montgomery on informed consent: an inexpert decision? AB - Montgomery v Lanarkshire HB is a deeply troubling decision when read closely. Paradoxically, its ruling supporting the principle of autonomy could be justified only by disregarding the individual patient's actual choices and characteristics in favour of a stereotype. The decision demonstrates a lack of expertise in dealing with specific clinical issues and misrepresents professional guidance. More fundamentally, it fails to appreciate the nature of professional expertise. This calls into question the competence of the courts to adjudicate on matters of clinical judgement and makes an attractive formulation of the test for disclosure obligations inherently unpredictable. PMID- 26811488 TI - HIV status: the prima facie right not to know the result. AB - When a patient regains consciousness from Cryptococcus meningitis, the clinician may offer an HIV test (in case it has not already been done) (scenario 1) or offer to tell the patient his HIV status (in case the test has already been performed with a positive result while the patient was unconscious) (scenario 2). Youngs and Simmonds proposed that the patient has the prima facie right to refuse an HIV test in scenario 1 but not the prima facie right not to be told the HIV status in scenario 2. I submit that the claims to the right of refusal in both scenarios are similarly strong as they should both be grounded in privacy, self determination or dignity. But a conscientious agent should bear in mind that members of the public also have the right not to be harmed. When the circumstance allows, a proper balance of the potential benefits and harm for all the competing parties should guide the clinical decision as to whose right should finally prevail. Where a full ethical analysis is not possible, the presumption should favour respecting the patient's right of refusal in both scenarios. PMID- 26811489 TI - The right not to know does not apply to HIV testing. PMID- 26811490 TI - The ethics of non-consensual HIV testing are not substantively different from the ethics of overriding the right not to know a test result. PMID- 26811492 TI - TSGDelta154-1054 splice variant increases TSG101 oncogenicity by inhibiting its E3-ligase-mediated proteasomal degradation. AB - Tumor susceptibility gene 101 (TSG101) elicits an array of cellular functions, including promoting cytokinesis, cell cycle progression and proliferation, as well as facilitating endosomal trafficking and viral budding. TSG101 protein is highly and aberrantly expressed in various human cancers. Specifically, a TSG101 splicing variant missing nucleotides 154 to 1054 (TSGDelta154-1054), which is linked to progressive tumor-stage and metastasis, has puzzled investigators for more than a decade. TSG101-associated E3 ligase (Tal)- and MDM2-mediated proteasomal degradation are the two major routes for posttranslational regulation of the total amount of TSG101. We reveal that overabundance of TSG101 results from TSGDelta154-1054 stabilizing the TSG101 protein by competitively binding to Tal, but not MDM2, thereby perturbing the Tal interaction with TSG101 and impeding subsequent polyubiquitination and proteasomal degradation of TSG101. TSGDelta154-1054 therefore specifically enhances TSG101-stimulated cell proliferation, clonogenicity, and tumor growth in nude mice. This finding shows the functional significance of TSGDelta154-1054 in preventing the ubiquitin proteasome proteolysis of TSG101, which increases tumor malignancy and hints at its potential as a therapeutic target in cancer treatment. PMID- 26811493 TI - Lentivirus-mediated PLCgamma1 gene short-hairpin RNA suppresses tumor growth and metastasis of human gastric adenocarcinoma. AB - Targeted molecular therapy has gradually been a potential solution in cancer therapy. Other authors' and our previous studies have demonstrated that phosphoinositide-specific phospholipase gamma (PLCgamma) is involved in regulating tumor growth and metastasis. However, the molecular mechanism underlying PLCgamma-dependent tumor growth and metastasis of gastric adenocarcinoma and whether PLCgamma may be a potential target for tumor therapy in human gastric adenocarcinoma are not yet well determined. Here, we investigated the role of PLCgamma inhibition in tumor growth and metastasis of human gastric adenocarcinoma using BGC-823 cell line and a nude mouse tumor xenograft model. The results manifested that the depletion of PLCgamma1 by the transduction with lentivirus-mediated PLCgamma1 gene short-hairpin RNA (shRNA) vector led to the decrease of tumor growth and metastasis of human gastric adenocarcinoma in vitro and in vivo. Furthermore, the Akt/Bad, Akt/S6, and ERK/Bad signal axes were involved in PLCgamma1-mediated tumor growth and metastasis of human gastric adenocarcinoma. Therefore, the abrogation of PLCgamma1 signaling by shRNA could efficaciously suppress human gastric adenocarcinoma tumor growth and metastasis, with important implication for validating PLCgamma1 as a potential target for human gastric adenocarcinoma. PMID- 26811494 TI - Genetic alterations and their clinical implications in gastric cancer peritoneal carcinomatosis revealed by whole-exome sequencing of malignant ascites. AB - Peritoneal carcinomatosis accompanied by malignant ascites is a major cause of death of advanced gastric cancer (GC). To comprehensively characterize the underlying genomic events involved in GC peritoneal carcinomatosis, we analyzed whole-exome sequences of normal gastric tissues, primary tumors, and malignant ascites from eight GC patients. We identified a unique mutational signature biased toward C-to-A substitutions in malignant ascites. In contrast, the patients who received treatment of adjuvant chemotherapy showed a high rate of C to-T substitutions along with hypermutation in malignant ascites. Comparative analysis revealed several candidate mutations for GC peritoneal carcinomatosis: recurrent mutations in COL4A6, INTS2, and PTPN13; mutations in druggable genes including TEP1, PRKCD, BRAF, ERBB4, PIK3CA, HDAC9, FYN, FASN, BIRC2, FLT3, ROCK1, CD22, and PIK3C2B; and mutations in metastasis-associated genes including TNFSF12, L1CAM, DIAPH3, ROCK1, TGFBR1, MYO9B, NR4A1, and RHOA. Notably, gene ontology analysis revealed the significant enrichment of mutations in the Rho ROCK signaling pathway-associated biological processes in malignant ascites. At least four of the eight patients acquired somatic mutations in the Rho-ROCK pathway components, suggesting the possible relevance of this pathway to GC peritoneal carcinomatosis. These results provide a genome-wide molecular understanding of GC peritoneal carcinomatosis and its clinical implications, thereby facilitating the development of effective therapeutics. PMID- 26811495 TI - Prognostic value of tumor-infiltrating lymphocytes for patients with completely resected stage IIIA(N2) non-small cell lung cancer. AB - BACKGROUND: The patient prognosis after complete resection for pathologic stage IIIA(N2) non-small cell lung cancer (NSCLC) remains a significant concern. The clinical relevance of the host immune response to NSCLC has yet to be established. We aimed to investigate the prognostic value of tumor-infiltrating lymphocytes (TILs) in a uniform cohort of patients with completely resected stage IIIA(N2) NSCLC. METHODS: From 2005 to 2012, consecutive patients with pathologic stage IIIA(N2) NSCLC who underwent complete resection at our institution were reviewed. For each case, full-face hematoxylin and eosin-stained sections from surgical specimens were evaluated for the TIL density. A published, recommended TIL scoring scale was followed. The patients were stratified into the TIL- or TIL+ group based on pathologic evaluation. RESULTS: Data from 320 patients were included in the analysis. Based on a median follow-up duration of 30.8 months, a higher density of TILs was associated with an improved postoperative survival time (P = 0.06). Subgroup analyses indicated that this positive effect was the greatest for patients with squamous cell carcinoma (SCC; P = 0.03). Among those with SCC, the TIL+ patients experienced a significantly increased 3-year distant metastasis-free survival (DMFS) compared to the TIL- patients (60.6% versus 42.7%, P = 0.02). Multivariate analyses of the 93 patients with SCC tumors confirmed that TIL+ was an independent prognostic factor for an increased DMFS (HR = 0.39, 95%CI 0.17-0.87, P = 0.02) and a prolonged overall survival (OS; HR = 0.47, 95%CI 0.22-1.00, P = 0.05). CONCLUSIONS: Our data suggest a potential role of TILs in predicting the survival of patients with completely resected stage IIIA(N2) NSCLC. The beneficial effects of TILs were more pronounced in the prediction of the DMFS and the OS in patients with SCC. This parameter should be considered for prospective inclusion in clinical trials. PMID- 26811496 TI - Hernandezine, a novel AMPK activator induces autophagic cell death in drug resistant cancers. AB - Drug resistance hinder most cancer chemotherapies and leads to disease recurrence and poor survival of patients. Resistance of cancer cells towards apoptosis is the major cause of these symptomatic behaviours. Here, we showed that isoquinoline alkaloids, including liensinine, isoliensinine, dauricine, cepharanthine and hernandezine, putatively induce cytotoxicity against a repertoire of cancer cell lines (HeLa, A549, MCF-7, PC3, HepG2, Hep3B and H1299). Proven by the use of apoptosis-resistant cellular models and autophagic assays, such isoquinoline alkaloid-induced cytotoxic effect involves energy- and autophagy-related gene 7 (Atg7)-dependent autophagy that resulted from direct activation of AMP activated protein kinase (AMPK). Hernandezine possess the highest efficacy in provoking such cell death when compared with other examined compounds. We confirmed that isoquinoline alkaloid is structurally varied from the existing direct AMPK activators. In conclusion, isoquinoline alkaloid is a new class of compound that induce autophagic cell death in drug-resistant fibroblasts or cancers by exhibiting its direct activation on AMPK. PMID- 26811497 TI - Targeting glucosylceramide synthase upregulation reverts sorafenib resistance in experimental hepatocellular carcinoma. AB - Evasive mechanisms triggered by the tyrosine kinase inhibitor sorafenib reduce its efficacy in hepatocellular carcinoma (HCC) treatment. Drug-resistant cancer cells frequently exhibit sphingolipid dysregulation, reducing chemotherapeutic cytotoxicity via the induction of ceramide-degrading enzymes. However, the role of ceramide in sorafenib therapy and resistance in HCC has not been clearly established. Our data reveals that ceramide-modifying enzymes, particularly glucosylceramide synthase (GCS), are upregulated during sorafenib treatment in hepatoma cells (HepG2 and Hep3B), and more importantly, in sorafenib-resistant cell lines. GCS silencing or pharmacological GCS inhibition sensitized hepatoma cells to sorafenib exposure. GCS inhibition, combined with sorafenib, triggered cytochrome c release and ATP depletion in sorafenib-treated hepatoma cells, leading to mitochondrial cell death after energetic collapse. Conversely, genetic GCS overexpression increased sorafenib resistance. Of interest, GCS inhibition improved sorafenib effectiveness in a xenograft mouse model, recovering drug sensitivity of sorafenib-resistant tumors in mice. In conclusion, our results reveal GCS induction as a mechanism of sorafenib resistance, suggesting that GCS targeting may be a novel strategy to increase sorafenib efficacy in HCC management, and point to target the mitochondria as the subcellular location where sorafenib therapy could be potentiated. PMID- 26811498 TI - A novel contribution of spvB to pathogenesis of Salmonella Typhimurium by inhibiting autophagy in host cells. AB - Salmonella plasmid virulence genes (spv) are highly conserved in strains of clinically important Salmonella serovars. It is essential for Salmonella plasmid correlated virulence, although the exact mechanism remains to be elucidated. Autophagy has been reported to play an important role in host immune responses limiting Salmonella infection. Our previous studies demonstrated that Salmonella conjugative plasmid harboring spv genes could enhance bacterial cytotoxicity by inhibiting autophagy. In the present study, we investigated whether spvB, which is one of the most important constituents of spv ORF could intervene in autophagy pathway. Murine macrophage-like cells J774A.1, human epithelial HeLa cells, and BALB/c mice infected with Salmonella Typhimurium wild type, mutant and complementary strains (carrying or free spvB or complemented only with ADP ribosyltransferase activity of SpvB) were used in vitro and in vivo assay, respectively. To further explore the molecular mechanisms, both SpvB ectopic eukaryotic expression system and cells deficient in essential autophagy components by siRNA were generated. Results indicated that spvB could suppress autophagosome formation through its function in depolymerizing actin, and aggravate inflammatory injury of the host in response to S. Typhimurium infection. Our studies demonstrated virulence of spvB involving in inhibition of autophagic flux for the first time, which could provide novel insights into Salmonella pathogenesis, and have potential application to develop new antibacterial strategies for Salmonellosis. PMID- 26811499 TI - Is BOK required for apoptosis induced by endoplasmic reticulum stress? PMID- 26811500 TI - WHAT ROLE SHOULD PUBLIC OPINION PLAY IN ETHICO-LEGAL DECISION MAKING? THE EXAMPLE OF SELECTING SEX FOR NON-MEDICAL REASONS USING PREIMPLANTATION GENETIC DIAGNOSIS. AB - In this article, we consider the prohibition on the use of preimplantation genetic diagnosis to select an embryo on the basis of its sex for non -: medical reasons. We use this as a case study to explore the role that public consultations have and should play in ethico-legal decision-making. Until the Human Fertilisation and Embryology Act 1990 was amended by the Human Fertilisation and Embryology Act 2008, non-medical sex selection of an embryo was not statutorily regulated, but it was the policy of the Human Fertilisation and Embryology Authority that such selection should not occur. However, since 2009, it has been a criminal offence to select an embryo on the basis of its sex for non-medical reasons. We consider the reasons given for this change and explore the role that 'public opinion' had in the decision-making process. On the face of it, asking the public what they think seems reasonable, fair and democratic, and those who are not in favour of public consultations being accorded great weight in matters of policy may appear out of touch and as wanting to impose their moral views on the public at large. But there are problems with doing so, especially when seeking to regulate ethically controversial issues. We discuss whether regulation should be influenced by public opinion obtained via 'public consultations', and utilise sex selection for non-medical reasons as an example of how (apparently) public opinion was used to support the criminalisation of this practice. PMID- 26811501 TI - Reply to Hart et al.: MINCR and MYC: More than expression correlation. PMID- 26811502 TI - MINCR is not a MYC-induced lncRNA. PMID- 26811503 TI - The Impact of Opioid Treatment on Regional Gastrointestinal Transit. AB - BACKGROUND/AIMS: To employ an experimental model of opioid-induced bowel dysfunction in healthy human volunteers, and evaluate the impact ofopioid treatment compared to placebo on gastrointestinal (GI) symptoms and motility assessed by questionnaires and regional GItransit times using the 3-dimensional (3D)-Transit system. METHODS: Twenty-five healthy males were randomly assigned to oxycodone or placebo for 5 days in a double blind, crossover design. AdverseGI effects were measured with the bowel function index, gastrointestinal symptom rating scale, patient assessment of constipationsymptom questionnaire, and Bristol stool form scale. Regional GI transit times were determined using the 3D Transit system, and segmental transit times in the colon were determined using a custom Matlab((r)) graphical user interface. RESULTS: GI symptom scores increased significantly across all applied GI questionnaires during opioid treatment. Oxycodone increased median total GI transit time from 22.2 to 43.9 hours (P < 0.001), segmental transit times in the cecum and ascending colon from 5.7 to 9.9 hours (P = 0.012), rectosigmoid colon transit from 2.7 to 9.0 hours (P = 0.044), and colorectal transit time from 18.6 to 38.6 hours (P= 0.001). No associations between questionnaire scores and segmental transit times were detected. CONCLUSIONS: Self-assessed GI adverse effects and increased GI transit times in different segments were induced during oxycodone treatment. This detailed information about segmental changes in motility has great potential for future interventional head-to-head trials of different laxative regimes for prevention and treatment of constipation. PMID- 26811504 TI - Efficacy of DA-9701 (Motilitone) in Functional Dyspepsia Compared to Pantoprazole: A Multicenter, Randomized, Double-blind, Non-inferiority Study. AB - BACKGROUND/AIMS: The effect of proton pump inhibitors (PPI) in Asian functional dyspepsia (FD) patients has not been well established as in Westerncountries. DA 9701, a novel prokinetic agent, stimulates gastric emptying and modulates visceral hypersensitivity in vivo and in human studies. This study was conducted to compare the efficacy of DA-9701 with a conventional PPI in mono or combination therapy in patients with FD. METHODS: In this double-blind, randomized, non inferiority trial, 389 patients diagnosed with FD using Rome III criteria were allocated among3 groups: 30-mg DA-9701 t.i.d (means 3 times a day), 40-mg pantoprazole, and 30-mg DA-9701 t.i.d + 40-mg pantoprazole. Theprimary efficacy end-point was a global assessment of the patient binary response or response on a 5-Likert scale after 4 weeks. RESULTS: The global symptomatic improvement was 60.5% in the DA-9701 group, 65.6% in the pantoprazole group, and 63.5% in the DA 9701 + pantoprazole group using a 5-Likert scale at week 4 with no significant difference among 3 groups (P = 0.685). Symptomimprovement measured by binary outcome was significantly achieved in each of the 3 groups, but not different among groups.Patients in all treatment groups reported significant improvement in the response rate and symptoms according to FD subtypes anddyspepsia-related quality of life (P < 0.001), but there were no significant differences among the 3 groups. CONCLUSIONS: DA-9701 improves global and individual symptoms and increases dyspepsia-specific quality of life in patients with FD. The efficacyof DA-9701 monotherapy is comparable with pantoprazole and there is no additive effect with combination of DA-9701 andpantoprazole in patients with FD. PMID- 26811505 TI - Role of UTS2 gene in the genetic susceptibility to atrial fibrillation in the Chinese population. AB - OBJECTIVE: Atrial fibrosis plays a key role in the inducibility and persistence of atrial fibrillation. Urotensin II (U-II/UTS2) induces cardiac fibrosis by increasing fibroblast collagen synthesis and increased U-II plasma levels have been reported in patients with atrial fibrosis. Our objective was therefore to evaluate the possible role of the UTS2 gene polymorphisms Thr21Met and Ser89Asn in the genetic susceptibility to atrial fibrillation in a Chinese population. METHODS: A case-control study was designed to compare the distribution of alleles and genotypes between controls (n=197) and patients with AF (n=197). The detection of UTS2 gene polymorphisms was undertaken using the PCR-restriction fragment length polymorphism technique. RESULTS: We identified statistically significant differences between the atrial fibrillation and control groups with regard to the frequency of genotype variant GA at the Ser89Asn locus (OR 1.955, 95% CI 1.071 to 3.566, p=0.029). When stratified by sex, differences in genotype distribution of polymorphism Ser89Asn was only seen in men in the additive tested inheritance model (OR 2.843, 95% CI 1.273 to 6.348, p=0.011). There was a statistical difference in Met21Met, implying a potential beneficial role for atrial fibrillation in the recessive tested inheritance model among men (OR 0.260, 95% CI 0.075 to 0.89, p=0.033; AA vs GA-GG). For subjects with atrial fibrillation, the Met21Met genotype was associated with a larger anteroposterior left atrial diameter (AA vs GG, 4.12+/-0.62 vs 3.86+/-0.51, p=0.028) and a smaller left ventricular end-diastolic diameter (AA vs GG, 4.50+/-0.48 vs 4.78+/ 0.49, p=0.039). CONCLUSIONS: Ser89Asn polymorphisms of the UTS2 gene are significantly associated with atrial fibrillation in the Chinese population. Additionally, we demonstrated that genotype Met21Met may have a potential beneficial role in atrial fibrillation. PMID- 26811506 TI - Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries: primary repair. AB - Primary repair of pulmonary atresia (PA) with ventricular septal defect (VSD) and major aortopulmonary collaterals based on single-stage unifocalization was first reported in 1995. From a midline approach, all collaterals are extensively dissected, translocated in front of the oesophagus and/or the trachea, when required, and directly anastomosed to each other or to the native pulmonary arteries, whenever present, without interposition of prosthetic material. The need for concomitant VSD closure is assessed intraoperatively with a pulmonary flow study according to a standardized protocol. Pulmonary blood supply is established by valved conduit interposition in all patients, regardless of the suitability for VSD closure. Palliation with systemic-pulmonary shunt is reserved for selected cases. Between 1994 and 2015, 94 patients with a median age of 1.09 years (range 0.03-19) underwent single-stage unifocalization at our institution. In 78 (82.1%) of them, an intraoperative pulmonary flow study was utilized to assess acceptability for concomitant VSD closure, which was accomplished in 69 cases (73%). Intraoperatively, following VSD closure, the mean right ventricle-to aortic pressure ratio was 0.49 +/- 0.14. The overall mortality rate was 11.2% (n = 10), with an 82% survival at 12.5 years. At a median follow-up interval of 5.8 years, the right ventricle-to-aortic pressure ratio did not differ significantly from the early postoperative phase. The surgical results of primary repair of PA with VSD and major aortopulmonary collaterals based on single-stage unifocalization and an intraoperative pulmonary flow study are satisfactory and durable, despite the need for repeated percutaneous or surgical reinterventions. PMID- 26811507 TI - Low-fidelity simulator for technical connection to the cardiopulmonary bypass. AB - The technical simulator proposed in this study is a low-cost, reusable, reproducible and portable tool to guide trainees at all levels in order to improve their surgical skills in connection with the cardiopulmonary bypass (CPB) circuit. The simulator is a self-made portable box that can be used for an unrestricted number of procedures. It is supplied with self-made anatomical replicas that have been tested to simulate the flexible property of the real anatomy. The building process is detailed in this study. PMID- 26811508 TI - Intermediate-fidelity simulator for self-training in mitral valve surgery. AB - Current training in mitral valve (MV) surgery is affected by many factors, among which are the complexity of surgical procedures and complex three-dimensional anatomy of the MV. An MV repair simulator is proposed in this study as a low cost, reusable and portable tool to guide trainees at all levels to effectively construct it with the aim of improving their surgical skills in major techniques of MV surgery in an intermediate-fidelity concept. The simulator is a self-made portable box that is supplied with a self-made silicone MV substitute to simulate the flexible property of MV components. The building process is detailed in this study. Surgical procedures were simulated to test the surgical handling. PMID- 26811509 TI - A comparison of the ethanol sensing properties of alpha-iron oxide nanostructures prepared via the sol-gel and electrospinning techniques. AB - Haematite (alpha-Fe2O3) nanostructures were synthesized via a Pechini sol-gel method (PSG) and an electrospinning (ES) technique. Their texture and morphology were investigated by scanning and transmission electron microscopy. alpha-Fe2O3 nanoparticles were obtained by the PSG method, whereas fibrous structures consisting of interconnected particles were synthesized through the ES technique. The crystallinity of the alpha-Fe2O3 nanostructures was also studied by means of x-ray diffraction and Raman spectroscopy. Gas-sensing devices were fabricated by printing the synthesized samples on ceramic substrates provided with interdigitated Pt electrodes. The sensors were tested towards low concentrations of ethanol in air in the temperature range (200-400 degrees C). The results show that the alpha-Fe2O3 nanostructures exhibit somewhat different gas-sensing properties and, interestingly, their sensing behaviour is strongly temperature dependent. The availability of active sites for oxygen chemisorption and the diffusion of the analyte gas within the sensing layer structure are hypothesized to be the key factors responsible for the different sensing behaviour observed. PMID- 26811510 TI - Republished review: Surgical management of aortic root disease in Marfan syndrome and other congenital disorders associated with aortic root aneurysms. AB - Elective root replacement in Marfan syndrome has improved life expectancy in affected patients. Three forms of surgery are now available: total root replacement (TRR) with a valved conduit, valve sparing root replacement (VSRR) and personalised external aortic root support (PEARS) with a macroporous mesh sleeve. TRR can be performed irrespective of aortic dimensions and a mechanical replacement valve is a secure and near certain means of correcting aortic valve regurgitation but has thromboembolic and bleeding risks. VSRR offers freedom from anticoagulation and attendant risks of bleeding but reoperation for aortic regurgitation runs at 1.3% per annum. A prospective multi-institutional study has found this to be an underestimate of the true rate of valve-related adverse events. PEARS conserves the aortic root anatomy and optimises the chance of maintaining valve function but average follow-up is under 5 years and so the long term results are yet to be determined. Patients are on average in their 30s and so the cumulative lifetime need for reoperation, and of any valve-related complications, are consequently substantial. With lowering surgical risk of prophylactic root replacement, the threshold for intervention has reduced progressively over 30 years to 4.5 cm and so an increasing number of patients who are not destined to have a dissection are now having root replacement. In evaluation of these three forms of surgery, the number needed to treat to prevent dissection and the balance of net benefit and harm in future patients must be considered. PMID- 26811511 TI - Clinical gist. PMID- 26811512 TI - Correction. PMID- 26811513 TI - Reply to S.A. Rum et al. PMID- 26811514 TI - Reply to F.C.M. Cananzi et al. PMID- 26811515 TI - Chemoradiotherapy in Gastric Cancer: A Door Ajar. PMID- 26811516 TI - Reply to W. Hryniuk et al. PMID- 26811517 TI - Psychiatric Disorders Impeding Weight Loss in Obese Breast Cancer Survivors. PMID- 26811518 TI - Instituting and Teaching Ethical Standards for Grateful Patient Fundraising. PMID- 26811519 TI - PROCLAIM: Randomized Phase III Trial of Pemetrexed-Cisplatin or Etoposide Cisplatin Plus Thoracic Radiation Therapy Followed by Consolidation Chemotherapy in Locally Advanced Nonsquamous Non-Small-Cell Lung Cancer. AB - PURPOSE: The phase III PROCLAIM study evaluated overall survival (OS) of concurrent pemetrexed-cisplatin and thoracic radiation therapy (TRT) followed by consolidation pemetrexed, versus etoposide-cisplatin and TRT followed by nonpemetrexed doublet consolidation therapy. PATIENTS AND METHODS: Patients with stage IIIA/B unresectable nonsquamous non-small-cell lung cancer randomly received (1:1) pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) intravenously every 3 weeks for three cycles plus concurrent TRT (60 to 66 Gy) followed by pemetrexed consolidation every 3 weeks for four cycles (arm A), or standard therapy with etoposide 50 mg/m(2) and cisplatin 50 mg/m(2) intravenously, every 4 weeks for two cycles plus concurrent TRT (60 to 66 Gy) followed by two cycles of consolidation platinum-based doublet chemotherapy (arm B). The primary objective was OS. The study was designed as a superiority trial with 80% power to detect an OS hazard ratio of 0.74 with a type 1 error of .05. RESULTS: Enrollment was stopped early because of futility. Five hundred ninety-eight patients were randomly assigned (301 to arm A, 297 to arm B) and 555 patients (283 in arm A, 272 in arm B) were treated. Arm A was not superior to arm B in terms of OS (hazard ratio, 0.98; 95% CI, 0.79 to 1.20; median, 26.8 v 25.0 months; P = .831). Arm A had a significantly lower incidence of any drug-related grade 3 to 4 adverse events (64.0% v 76.8%; P = .001), including neutropenia (24.4% v 44.5%; P < .001), during the overall treatment period. CONCLUSION: Pemetrexed-cisplatin combined with TRT followed by consolidation pemetrexed was not superior to standard chemoradiotherapy for stage III unresectable nonsquamous non-small-cell lung cancer. PMID- 26811521 TI - Financial Insolvency as a Risk Factor for Early Mortality Among Patients With Cancer. AB - PURPOSE: Patients with cancer are more likely to file for bankruptcy than the general population, but the impact of severe financial distress on health outcomes among patients with cancer is not known. METHODS: We linked Western Washington SEER Cancer Registry records with federal bankruptcy records for the region. By using propensity score matching to account for differences in several demographic and clinical factors between patients who did and did not file for bankruptcy, we then fit Cox proportional hazards models to examine the relationship between bankruptcy filing and survival. RESULTS: Between 1995 and 2009, 231,596 persons were diagnosed with cancer. Patients who filed for bankruptcy (n = 4,728) were more likely to be younger, female, and nonwhite, to have local- or regional- (v distant-) stage disease at diagnosis, and have received treatment. After propensity score matching, 3,841 patients remained in each group (bankruptcy v no bankruptcy). In the matched sample, mean age was 53.0 years, 54% were men, mean income was $49,000, and majorities were white (86%), married (60%), and urban (91%) and had local- or regional-stage disease at diagnosis (84%). Both groups received similar initial treatments. The adjusted hazard ratio for mortality among patients with cancer who filed for bankruptcy versus those who did not was 1.79 (95% CI, 1.64 to 1.96). Hazard ratios varied by cancer type: colorectal, prostate, and thyroid cancers had the highest hazard ratios. Excluding patients with distant-stage disease from the models did not have an effect on results. CONCLUSION: Severe financial distress requiring bankruptcy protection after cancer diagnosis appears to be a risk factor for mortality. Further research is needed to understand the process by which extreme financial distress influences survival after cancer diagnosis and to find strategies that could mitigate this risk. PMID- 26811520 TI - Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies That Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease. AB - PURPOSE: Progressive malignancy is the leading cause of death after allogeneic hematopoietic stem-cell transplantation (alloHSCT). After alloHSCT, B-cell malignancies often are treated with unmanipulated donor lymphocyte infusions (DLIs) from the transplant donor. DLIs frequently are not effective at eradicating malignancy and often cause graft-versus-host disease, a potentially lethal immune response against normal recipient tissues. METHODS: We conducted a clinical trial of allogeneic T cells genetically engineered to express a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19. Patients with B-cell malignancies that had progressed after alloHSCT received a single infusion of CAR T cells. No chemotherapy or other therapies were administered. The T cells were obtained from each recipient's alloHSCT donor. RESULTS: Eight of 20 treated patients obtained remission, which included six complete remissions (CRs) and two partial remissions. The response rate was highest for acute lymphoblastic leukemia, with four of five patients obtaining minimal residual disease-negative CR. Responses also occurred in chronic lymphocytic leukemia and lymphoma. The longest ongoing CR was more than 30 months in a patient with chronic lymphocytic leukemia. New-onset acute graft-versus-host disease after CAR T-cell infusion developed in none of the patients. Toxicities included fever, tachycardia, and hypotension. Peak blood CAR T-cell levels were higher in patients who obtained remissions than in those who did not. Programmed cell death protein-1 expression was significantly elevated on CAR T cells after infusion. Presence of blood B cells before CAR T-cell infusion was associated with higher postinfusion CAR T cell levels. CONCLUSION: Allogeneic anti-CD19 CAR T cells can effectively treat B cell malignancies that progress after alloHSCT. The findings point toward a future when antigen-specific T-cell therapies will play a central role in alloHSCT. PMID- 26811522 TI - Comparing Intelligence Quotient Change After Treatment With Proton Versus Photon Radiation Therapy for Pediatric Brain Tumors. AB - PURPOSE: Compared with photon radiation (XRT), proton beam radiation therapy (PBRT) reduces dose to normal tissues, which may lead to better neurocognitive outcomes. We compared change in intelligence quotient (IQ) over time in pediatric patients with brain tumors treated with PBRT versus XRT. PATIENTS AND METHODS: IQ scores were available for 150 patients (60 had received XRT, 90 had received PBRT). Linear mixed models examined change in IQ over time since radiation therapy (RT) by RT group, controlling for demographic/clinical characteristics. Craniospinal and focal RT subgroups were also examined. RESULTS: In the PBRT group, no change in IQ over time was identified (P = .130), whereas in the XRT group, IQ declined by 1.1 points per year (P = .004). IQ slopes did not differ between groups (P = .509). IQ was lower in the XRT group (by 8.7 points) versus the PBRT group (P = .011). In the craniospinal subgroup, IQ remained stable in both the PBRT (P = .203) and XRT groups (P = .060), and IQ slopes did not differ (P = .890). IQ was lower in the XRT group (by 12.5 points) versus the PBRT group (P = .004). In the focal subgroup, IQ scores remained stable in the PBRT group (P = .401) but declined significantly in the XRT group by 1.57 points per year (P = .026). IQ slopes did not differ between groups (P = .342). CONCLUSION: PBRT was not associated with IQ decline or impairment, yet IQ slopes did not differ between the PBRT and XRT groups. It remains unclear if PBRT results in clinically meaningful cognitive sparing that significantly exceeds that of modern XRT protocols. Additional long-term data are needed to fully understand the neurocognitive impact of PBRT in survivors of pediatric brain tumors. PMID- 26811523 TI - Hepatocellular Carcinoma in Children: Does Modified Platinum- and Doxorubicin Based Chemotherapy Increase Tumor Resectability and Change Outcome? Lessons Learned From the SIOPEL 2 and 3 Studies. AB - INTRODUCTION: The aim of this article is to present an experience of two prospective studies from the International Childhood Liver Tumor Strategy Group (SIOPEL 2 [S2] and SIOPEL [S3]) trials and to evaluate whether modified platinum- and doxorubicin-based chemotherapy is capable of increasing tumor resectability and changing patient outcomes. METHODS: Between 1995 and 2006, 20 patients with hepatocellular carcinoma (HCC) were included in the S2 trial and 70 were included in the S3 trial. Eighty-five patients remained evaluable. RESULTS: Response to preoperative chemotherapy was observed in 29 of 72 patients (40%) who did not have primary surgery, whereas 13 patients underwent upfront surgery. Thirty-three patients had a delayed resection. Thirty-nine tumors never became resectable. Complete tumor resection was achieved in 34 patients (40%), including seven of those treated with liver transplantation (LTX). After a median follow-up period of 75 months, 63 patients (74%) had an event (a progression during treatment, a relapse after treatment, or death from any cause). Sixty patients died. Twenty three of 46 patients (50%) who underwent tumor resection died. Eighteen of 27 patients (63%) with complete tumor resection (without LTX) and 20 of 34 patients (59%) with LTX survived. Only one of seven patients (14%) with microscopically involved margins survived. Overall survival at 5 years was 22%. CONCLUSION: Survival in pediatric HCC is more likely when complete tumor resection can be achieved. Intensification of platinum agents in the S2 and S3 trials has not resulted in improved survival. New treatment approaches in pediatric HCC should be postulated. PMID- 26811524 TI - Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial. AB - PURPOSE: To compare single-agent gemtuzumab ozogamicin (GO) with best supportive care (BSC) including hydroxyurea as first-line therapy in older patients with acute myeloid leukemia unsuitable for intensive chemotherapy. PATIENTS AND METHODS: In this trial, patients at least 61 years old were centrally randomized (1:1) to receive either a single induction course of GO (6 mg/m(2) on day 1 and 3 mg/m(2) on day 8) or BSC. Patients who did not progress after GO induction could receive up to eight monthly infusions of the immunoconjugate at 2 mg/m(2). Randomization was stratified by age, WHO performance score, CD33 expression status, and center. The primary end point was overall survival (OS) by intention to-treat analysis. RESULTS: A total of 237 patients were randomly assigned (118 to GO and 119 to BSC). The median OS was 4.9 months (95% CI, 4.2 to 6.8 months) in the GO group and 3.6 months (95% CI, 2.6 to 4.2 months) in the BSC group (hazard ratio, 0.69; 95% CI, 0.53 to 0.90; P = .005); the 1-year OS rate was 24.3% with GO and 9.7% with BSC. The OS benefit with GO was consistent across most subgroups, and was especially apparent in patients with high CD33 expression status, in those with favorable/intermediate cytogenetic risk profile, and in women. Overall, complete remission (CR [complete remission] + CRi [CR with incomplete recovery of peripheral blood counts]) occurred in 30 of 111 (27%) GO recipients. The rates of serious adverse events (AEs) were similar in the two groups, and no excess mortality from AEs was observed with GO. CONCLUSION: First line monotherapy with low-dose GO, as compared with BSC, significantly improved OS in older patients with acute myeloid leukemia who were ineligible for intensive chemotherapy. No unexpected AEs were identified and toxicity was manageable. PMID- 26811525 TI - Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib. AB - PURPOSE: To report the overall survival (OS) and clinical characteristics of BRAF inhibitor-naive long-term responders and survivors treated with dabrafenib plus trametinib in a phase I and II study of patients with BRAF V600 mutation-positive metastatic melanoma. METHODS: BRAF inhibitor-naive patients treated with dabrafenib 150 mg twice daily plus trametinib 2 mg daily (the 150/2 group) from the non-randomly assigned (part B) and randomly assigned (part C) cohorts of the study were analyzed for progression-free and OS separately. Baseline characteristics and factors on treatment were analyzed for associations with durable responses and OS. RESULTS: For BRAF inhibitor-naive patients in the 150/2 groups (n = 78), the progression-free survival at 1, 2, and 3 years was 44%, 22%, and 18%, respectively, for part B (n = 24) and 41%, 25%, and 21%, respectively, for part C (n = 54). Median OS was 27.4 months in part B and 25 months in part C. OS at 1, 2, and 3 years was 72%, 60%, and 47%, respectively, for part B and 80%, 51%, and 38%, respectively, for part C. Prolonged survival was associated with metastases in fewer than three organ sites and lower baseline lactate dehydrogenase. OS at 3 years was 62% in patients with normal baseline lactate dehydrogenase and 63% in patients with a complete response. CONCLUSION: Dabrafenib plus trametinib results in a median OS of more than 2 years in BRAF inhibitor-naive patients with BRAF V600 mutation-positive metastatic melanoma, and approximately 20% were progression free at 3 years. Durable responses occurred in patients with good prognostic features at baseline, which may be predictive. PMID- 26811526 TI - Proton Beam Radiation Therapy: The Future May Prove Brighter for Pediatric Patients With Brain Tumors. PMID- 26811527 TI - Cigarette Smoking Before and After Breast Cancer Diagnosis: Mortality From Breast Cancer and Smoking-Related Diseases. AB - PURPOSE: Cigarette smoking increases overall mortality, but it is not established whether smoking is associated with breast cancer prognosis. METHODS: We evaluated the association between smoking status before and after breast cancer diagnosis and mortality in the Collaborative Breast Cancer and Women's Longevity Study, a population-based prospective observational study conducted in Wisconsin, New Hampshire, and Massachusetts. Participants included 20,691 women, ages 20 to 79 years, diagnosed with incident localized or regional invasive breast cancer between 1988 and 2008; a subset of 4,562 of these women were recontacted a median of 6 years after diagnosis. Hazard ratios (HRs) with 95% CIs were calculated according to smoking status for death as a result of breast cancer; cancers of the lung, pharynx, or intrathoracic organs; other cancer; respiratory disease; and cardiovascular disease. RESULTS: During a median of 12 years, 6,778 women died, including 2,894 who died as a result of breast cancer. Active smokers 1 year before breast cancer diagnosis were more likely than never smokers to die of breast cancer (HR, 1.25; 95% CI, 1.13 to 1.37), respiratory cancer (HR, 14.48; 95% CI, 9.89 to 21.21), other respiratory disease (HR, 6.02; 95% CI, 4.55 to 7.97), and cardiovascular disease (HR, 2.08; 95% CI, 1.80 to 2.41). The 10% of women who continued to smoke after diagnosis were more likely than never smokers to die of breast cancer (HR, 1.72; 95% CI, 1.13 to 2.60). When compared with women who continued to smoke after diagnosis, those who quit smoking after diagnosis had lower mortality from breast cancer (HR, 0.67; 95% CI, 0.38 to 1.19) and respiratory cancer (HR, 0.39; 95% CI, 0.16 to 0.95). CONCLUSION: Smoking before or after diagnosis was associated with a higher mortality from breast cancer and several other causes. PMID- 26811528 TI - Improved Axillary Evaluation Following Neoadjuvant Therapy for Patients With Node Positive Breast Cancer Using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection. AB - PURPOSE: Placing clips in nodes with biopsy-confirmed metastasis before initiating neoadjuvant therapy allows for evaluation of response in breast cancer. Our goal was to determine if pathologic changes in clipped nodes reflect the status of the nodal basin and if targeted axillary dissection (TAD), which includes sentinel lymph node dissection (SLND) and selective localization and removal of clipped nodes, improves the false-negative rate (FNR) compared with SLND alone. METHODS: A prospective study of patients with biopsy-confirmed nodal metastases with a clip placed in the sampled node was performed. After neoadjuvant therapy, patients underwent axillary surgery and the pathology of the clipped node was compared with other nodes. Patients undergoing TAD had SLND and selective removal of the clipped node using iodine-125 seed localization. The FNR was determined in patients undergoing complete axillary lymphadenectomy (ALND). RESULTS: Of 208 patients enrolled in this study, 191 underwent ALND, with residual disease identified in 120 (63%). The clipped node revealed metastases in 115 patients, resulting in an FNR of 4.2% (95% CI, 1.4 to 9.5) for the clipped node. In patients undergoing SLND and ALND (n = 118), the FNR was 10.1% (95% CI, 4.2 to 19.8), which included seven false-negative events in 69 patients with residual disease. Adding evaluation of the clipped node reduced the FNR to 1.4% (95% CI, 0.03 to 7.3; P = .03). The clipped node was not retrieved as an SLN in 23% (31 of 134) of patients, including six with negative SLNs but metastasis in the clipped node. TAD followed by ALND was performed in 85 patients, with an FNR of 2.0% (1 of 50; 95% CI, 0.05 to 10.7). CONCLUSION: Marking nodes with biopsy confirmed metastatic disease allows for selective removal and improves pathologic evaluation for residual nodal disease after chemotherapy. PMID- 26811529 TI - Impact of Patient Factors on Recurrence Risk and Time Dependency of Oxaliplatin Benefit in Patients With Colon Cancer: Analysis From Modern-Era Adjuvant Studies in the Adjuvant Colon Cancer End Points (ACCENT) Database. AB - PURPOSE: Fluorouracil plus leucovorin (FU + LV) adjuvant chemotherapy reduced the risk of recurrence and death across all time points in a pooled analysis of 20,898 patients with colon cancer from 18 randomized studies. The impact of oxaliplatin added to FU + LV on the time course of recurrence and survival remains unknown. PATIENTS AND METHODS: A total of 12,233 patients enrolled to the randomized trials C-07, C-08, N0147, MOSAIC (Adjuvant Treatment of Colon Cancer), and XELOXA (Adjuvant XELOX) were pooled to examine the impact of oxaliplatin and tumor-specific factors on the time course of recurrence and death. For each end point, continuous-time risk was modeled over 6 years post treatment in all oxaliplatin-treated patients and patients concurrently randomized to FU + LV with or without oxaliplatin; the latter analyses supported time-dependent treatment comparisons. RESULTS: Addition of oxaliplatin significantly reduced the risk of recurrence within the first 14 months post treatment for patients with stage II disease and within the first 4 years for patients with stage III disease. Oxaliplatin also significantly reduced risk of death from 2 to 6 years post treatment for patients with stage III disease, with no differences in timing of outcomes between treatment groups (ie, oxaliplatin did not simply postpone recurrence or death compared with FU + LV alone). Patients with stage II disease receiving oxaliplatin did not exhibit a significant reduction in risk of death in the first 6 years post treatment. Recurrence risk peaked near 14 months for both treatments, and risk of recurrence and death increased with increased tumor and nodal burden. CONCLUSIONS: These analyses support the addition of oxaliplatin to fluoropyrimidine-based adjuvant therapy in patients with stage III disease and underscore the need for adequate surveillance of patients with colon cancer during the first 3 years after adjuvant therapy. PMID- 26811531 TI - Hearing Loss in Patients Who Received Cranial Radiation Therapy for Childhood Cancer. AB - PURPOSE: Patients treated with cranial radiation therapy (RT) are at risk for sensorineural hearing loss (SNHL). Although SNHL is often characterized as a delayed consequence of anticancer therapy, longitudinal reports of SNHL in childhood cancer survivors treated with contemporary RT are limited. We report the incidence, onset, severity, and long-term trajectory of SNHL among children receiving RT. Potential risk factors for SNHL were also identified. PATIENTS AND METHODS: Serial audiologic testing was conducted on 235 pediatric patients who were treated with conformal or intensity-modulated RT as part of an institutional phase II trial for localized primary brain tumors, including craniopharyngioma, ependymoma, and juvenile pilocytic astrocytoma. All but one patient had measurable cochlear radiation dose (CRD) greater than 0 Gy. The median follow-up from RT initiation to latest audiogram was 9 years with a median of 11 post-RT audiograms per patient. Audiograms were classified by the Chang Ototoxicity Grading Scale. Progression was defined by an increase in Chang grade from SNHL onset to the most recent evaluation. RESULTS: At last evaluation, SNHL was prevalent in 14% of patients: 2.1% had mild and 11.9% had significant SNHL requiring hearing aids. Median time from RT to SNHL onset was 3.6 years (range, 0.4 to 13.2 years). Among 29 patients with follow-up evaluations after SNHL onset, 65.5% experienced continued decline in hearing sensitivity in either ear and 34.5% had no change. Younger age at RT initiation (hazard ratio [HR], 2.32; 95% CI, 1.21 to 4.46), higher CRD (HR, 1.07; 95% CI, 1.03 to 1.11), and cerebrospinal fluid shunting (HR, 2.02; 95% CI, 1.07 to 3.78) were associated with SNHL. CONCLUSION: SNHL is a late effect of RT that likely worsens over time. Long-term audiologic follow-up for a minimum of 10 years post-RT is recommended. PMID- 26811532 TI - Definitions, End Points, and Clinical Trial Designs for Non-Muscle-Invasive Bladder Cancer: Recommendations From the International Bladder Cancer Group. AB - PURPOSE: To provide recommendations on appropriate clinical trial designs in non muscle-invasive bladder cancer (NMIBC) based on current literature and expert consensus of the International Bladder Cancer Group. METHODS: We reviewed published trials, guidelines, meta-analyses, and reviews and provided recommendations on eligibility criteria, baseline evaluations, end points, study designs, comparators, clinically meaningful magnitude of effect, and sample size. RESULTS: NMIBC trials must be designed to provide the most clinically relevant data for the specific risk category of interest (low, intermediate, or high). Specific eligibility criteria and baseline evaluations depend on the risk category being studied. For the population of patients for whom bacillus Calmette Guerin (BCG) has failed, the type of failure (BCG unresponsive, refractory, relapsing, or intolerant) should be clearly defined to make comparisons across trials feasible. Single-arm designs may be relevant for the BCG-unresponsive population. Here, a clinically meaningful initial complete response rate (for carcinoma in situ) or recurrence-free rate (for papillary tumors) of at least 50% at 6 months, 30% at 12 months, and 25% at 18 months is recommended. For other risk levels, randomized superiority trial designs are recommended; noninferiority trials are to be used sparingly given the large sample size required. Placebo control is considered unethical for all intermediate- and high-risk strata; therefore, control arms should comprise the current guideline-recommended standard of care for the respective risk level. In general, trials should use time to recurrence or recurrence-free survival as the primary end point and time to progression, toxicity, disease-specific survival, and overall survival as potential secondary end points. Realistic efficacy thresholds should be set to ensure that novel therapies receive due review by regulatory bodies. CONCLUSION: The International Bladder Cancer Group has developed formal recommendations regarding definitions, end points, and clinical trial designs for NMIBC to encourage uniformity among studies in this disease. PMID- 26811533 TI - Serum Human Epidermal Growth Factor 2 Extracellular Domain as a Predictive Biomarker for Lapatinib Treatment Efficacy in Patients With Advanced Breast Cancer. AB - PURPOSE: We examined the prognostic and predictive value of serum human epidermal growth factor 2 (HER2) extracellular domain (sHER2) in patients with advanced breast cancer treated with lapatinib using data from three randomized trials. PATIENTS AND METHODS: We analyzed sHER2 and tissue HER2 (tHER2) data from 1,902 patients (84%) who were randomly assigned to receive lapatinib or control in the trials EGF30001, EGF30008, and EGF100151. Cox regression analyses were performed to correlate both biomarkers with progression-free survival (PFS) and overall survival (OS). RESULTS: Median sHER2 levels were 25.1 and 10.1 ng/mL in tHER2 amplified (tHER-positive) and nonamplified (tHER-negative) populations, respectively (r = 0.42 for sHER2-tHER2 correlation). Lapatinib had significant PFS benefit over control (hazard ratio [HR], 0.855; P = .004), but not OS (HR, 0.941; P = .33). Lapatinib PFS benefit is independently predicted by higher sHER2 values (HR per 10-ng/mL increase in sHER2: lapatinib-containing therapies, 1.009 v nonlapatinib-containing therapies, 1.044; P(interaction) < .001) and by positive tHER2 (HR [lapatinib v nonlapatinib]: tHER2 positive, 0.638 v tHER2 negative, 0.940; P(interaction) = .001). Within the tHER2-positive subpopulation (n = 515), higher sHER2 values still independently predicted lapatinib PFS benefit (HR per 10-ng/mL increase in sHER2: lapatinib-containing therapies, 1.017 v nonlapatinib-containing therapies, 1.041; P(interaction) = .008). In control arms (n = 936), higher sHER2 was associated with worse prognosis in multivariable analyses (PFS HR per 10 ng/mL: PFS, 1.024; P < .001; and OS, 1.018; P < .001). CONCLUSION: Higher sHER2 predicts greater PFS benefit with lapatinib independent of tHER2 status. High sHER2 is also independently prognostic for worse survival in patients who received nonlapatinib-containing therapies. The predictive role of sHER2 for other anti-HER2 agents requires further research. PMID- 26811534 TI - CELF4 Variant and Anthracycline-Related Cardiomyopathy: A Children's Oncology Group Genome-Wide Association Study. AB - PURPOSE: Interindividual variability in the dose-dependent association between anthracyclines and cardiomyopathy suggests that genetic susceptibility could play a role. The current study uses an agnostic approach to identify genetic variants that could modify cardiomyopathy risk. METHODS: A genome-wide association study was conducted in childhood cancer survivors with and without cardiomyopathy (cases and controls, respectively). Single-nucleotide polymorphisms (SNPs) that surpassed a prespecified threshold for statistical significance were independently replicated. The possible mechanistic significance of validated SNP(s) was sought by using healthy heart samples. RESULTS: No SNP was marginally associated with cardiomyopathy. However, SNP rs1786814 on the CELF4 gene passed the significance cutoff for gene-environment interaction (Pge = 1.14 * 10(-5)). Multivariable analyses adjusted for age at cancer diagnosis, sex, anthracycline dose, and chest radiation revealed that, among patients with the A allele, cardiomyopathy was infrequent and not dose related. However, among those exposed to greater than 300 mg/m(2) of anthracyclines, the rs1786814 GG genotype conferred a 10.2-fold (95% CI, 3.8- to 27.3-fold; P < .001) increased risk of cardiomyopathy compared with those who had GA/AA genotypes and anthracycline exposure of 300 mg/m(2) or less. This gene-environment interaction was successfully replicated in an independent set of anthracycline-related cardiomyopathy. CUG-BP and ETR-3-like factor proteins control developmentally regulated splicing of TNNT2, the gene that encodes for cardiac troponin T (cTnT), a biomarker of myocardial injury. Coexistence of more than one cTnT variant results in a temporally split myofilament response to calcium, which causes decreased contractility. Analysis of TNNT2 splicing variants in healthy human hearts suggested an association between the rs1786814 GG genotype and coexistence of more than one TNNT2 splicing variant (90.5% GG v 41.7% GA/AA; P = .005). CONCLUSION: We report a modifying effect of a polymorphism of CELF4 (rs1786814) on the dose-dependent association between anthracyclines and cardiomyopathy, which possibly occurs through a pathway that involves the expression of abnormally spliced TNNT2 variants. PMID- 26811535 TI - Enzalutamide Versus Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE Trial. AB - PURPOSE: Enzalutamide, a potent oral androgen receptor inhibitor, improves survival in men with metastatic castration-resistant prostate cancer (CRPC) before and after chemotherapy. Bicalutamide, a nonsteroidal antiandrogen, is widely used to treat men with nonmetastatic or metastatic CRPC. The efficacy and safety of these drugs were compared in this randomized, double-blind, phase II study of men with CRPC. PATIENTS AND METHODS: A total of 396 men with nonmetastatic (n = 139) or metastatic (n = 257) CRPC were randomly assigned to enzalutamide 160 mg per day (n = 198) or bicalutamide 50 mg per day (n = 198). Androgen deprivation therapy was continued in both arms. The primary end point was progression-free survival (PFS). RESULTS: Enzalutamide reduced the risk of progression or death by 76% compared with bicalutamide (hazard ratio [HR], 0.24; 95% CI, 0.18 to 0.32; P < .001). Median PFS was 19.4 months with enzalutamide versus 5.7 months with bicalutamide. Enzalutamide resulted in significant improvements in all key secondary end points: time to prostate-specific antigen progression (HR, 0.19; 95% CI, 0.14 to 0.26; P < .001); proportion of patients with a >= 50% prostate-specific antigen response (81% v 31%; P < .001); and radiographic PFS in metastatic patients (HR, 0.32; 95% CI, 0.21 to 0.50; P < .001). Beneficial effects with enzalutamide were observed in both nonmetastatic and metastatic subgroups. The observed adverse event profile was consistent with that from phase III enzalutamide trials. CONCLUSION: Enzalutamide significantly reduced risk of prostate cancer progression or death compared with bicalutamide in patients with nonmetastatic or metastatic CRPC. PMID- 26811537 TI - The lipidome associated with the gamma-secretase complex is required for its integrity and activity. AB - gamma-Secretase is a multi-subunit membrane protease complex that catalyses the final intramembrane cleavage of the beta-amyloid precursor protein (APP) during the neuronal production of amyloid-beta peptides (Abeta), which are implicated as the causative agents of Alzheimer's disease (AD). In the present study, we report the reconstitution of a highly purified, active gamma-secretase complex into proteoliposomes without exogenous lipids and provide the first direct evidence for the existence of a microenvironment of 53 molecular species from 11 major lipid classes specifically associated with the gamma-secretase complex, including phosphatidylcholine and cholesterol. Importantly, we demonstrate that the pharmacological modulation of certain phospholipids abolishes both the integrity and the enzymatic activity of the intramembrane protease. Together, our findings highlight the importance of a specific lipid microenvironment for the structure and function of gamma-secretase. PMID- 26811536 TI - The function of orthologues of the human Parkinson's disease gene LRRK2 across species: implications for disease modelling in preclinical research. AB - In the period since LRRK2 (leucine-rich repeat kinase 2) was identified as a causal gene for late-onset autosomal dominant parkinsonism, a great deal of work has been aimed at understanding whether the LRRK2 protein might be a druggable target for Parkinson's disease (PD). As part of this effort, animal models have been developed to explore both the normal and the pathophysiological roles of LRRK2. However, LRRK2 is part of a wider family of proteins whose functions in different organisms remain poorly understood. In this review, we compare the information available on biochemical properties of LRRK2 homologues and orthologues from different species from invertebrates (e.g. Caenorhabditis elegans and Drosophila melanogaster) to mammals. We particularly discuss the mammalian LRRK2 homologue, LRRK1, and those species where there is only a single LRRK homologue, discussing examples where each of the LRRK family of proteins has distinct properties as well as those cases where there appear to be functional redundancy. We conclude that uncovering the function of LRRK2 orthologues will help to elucidate the key properties of human LRRK2 as well as to improve understanding of the suitability of different animal models for investigation of LRRK2-related PD. PMID- 26811538 TI - Sigma-1 receptors: a new pathway for the modulation of store-operated calcium entry. AB - SOCE (store-operated Ca(2+) entry) is a ubiquitous mechanism for Ca(2+) influx in animal cells. In a recent issue of the Biochemical Journal, Brailoiu and colleagues reported that cocaine attenuates SOCE in rat brain microvascular endothelial cells, via a mechanism that requires the expression and activation of the sigma-1 receptor, a chaperone located in the endoplasmic reticulum mitochondrion interface that modulates intracellular Ca(2+) homoeostasis and cell survival. This study envisages a pathway through which cocaine modulates endothelial function via regulation of SOCE. The regulation of SOCE by sigma-1 receptors provides a novel and important pathway in Ca(2+) signalling. PMID- 26811539 TI - Sitagliptin decreases ventricular arrhythmias by attenuated glucose-dependent insulinotropic polypeptide (GIP)-dependent resistin signalling in infarcted rats. AB - Myocardial infarction (MI) was associated with insulin resistance, in which resistin acts as a critical mediator. We aimed to determine whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, can attenuate arrhythmias by regulating resistin-dependent nerve growth factor (NGF) expression in postinfarcted rats. Normoglycaemic male Wistar rats after ligating coronary artery were randomized to either vehicle or sitagliptin for 4 weeks starting 24 h after operation. Post-infarction was associated with increased myocardial noradrenaline [norepinephrine (NE)] levels and sympathetic hyperinnervation. Compared with vehicle, sympathetic innervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis of tyrosine hydroxylase, growth-associated factor 43 and neurofilament and western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the sitagliptin-treated infarcted rats were significantly lower than those in vehicle. Furthermore, sitagliptin was associated with reduced resistin expression and increased Akt activity. Ex vivo studies showed that glucose-dependent insulinotropic polypeptide (GIP) infusion, but not glucagon-like peptide-1 (GLP-1), produced similar reduction in resistin levels to sitagliptin in postinfarcted rats. Furthermore, the attenuated effects of sitagliptin on NGF levels can be reversed by wortmannin (a phosphatidylinositol 3-kinase antagonist) and exogenous resistin infusion. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation in the non-diabetic infarcted rats. Sitagliptin attenuated resistin expression via the GIP-dependent pathway, which inhibited sympathetic innervation through a signalling pathway involving phosphatidylinositol 3-kinase (PI3K) and Akt protein. PMID- 26811540 TI - Interleukin-1beta induces fibroblast growth factor 2 expression and subsequently promotes endothelial progenitor cell angiogenesis in chondrocytes. AB - Arthritis is a process of chronic inflammation that results in joint damage. IL (interleukin)-1beta is an inflammatory cytokine that acts as a key mediator of cartilage degradation, and is abundantly expressed in arthritis. Neovascularization is one of the pathological characteristics of arthritis. However, the role of IL-1beta in the angiogenesis of chondrocytes remains unknown. In the present study, we demonstrate that stimulating chondrocytes (ATDC5) with IL-1beta increased the expression of FGF (fibroblast growth factor) 2, a potent angiogenic inducer, and then promoted EPC (endothelial progenitor cell) tube formation and migration. In addition, FGF-2-neutralizing antibody abolished ATDC5-conditional medium-mediated angiogenesis in vitro, as well as its angiogenic effects in the CAM (chick chorioallantoic membrane) assay and Matrigel plug nude mice model in vivo. IHC (immunohistochemistry) staining from a CIA (collagen-induced arthritis) mouse model also demonstrates that arthritis increased the expression of IL-1beta and FGF-2, as well as EPC homing in articular cartilage. Moreover, IL-1beta-induced FGF-2 expression via IL-1RI (type 1 IL-1 receptor), ROS (reactive oxygen species) generation, AMPK (AMP-activated protein kinase), p38 and NF-kappaB (nuclear factor kappaB) pathway has been demonstrated. On the basis of these findings, we conclude that IL-1beta promotes FGF-2 expression in chondrocytes through the ROS/AMPK/p38/NF-kappaB signalling pathway and subsequently increases EPC angiogenesis. Therefore IL-1beta serves as a link between inflammation and angiogenesis during arthritis. PMID- 26811542 TI - Safety climate strength: a promising construct for safety research and practice. PMID- 26811541 TI - Reporting and design elements of audit and feedback interventions: a secondary review. AB - BACKGROUND: Audit and feedback (A&F) is a frequently used intervention aiming to support implementation of research evidence into clinical practice with positive, yet variable, effects. Our understanding of effective A&F has been limited by poor reporting and intervention heterogeneity. Our objective was to describe the extent of these issues. METHODS: Using a secondary review of A&F interventions and a consensus-based process to identify modifiable A&F elements, we examined intervention descriptions in 140 trials of A&F to quantify reporting limitations and describe the interventions. RESULTS: We identified 17 modifiable A&F intervention elements; 14 were examined to quantify reporting limitations and all 17 were used to describe the interventions. Clear reporting of the elements ranged from 56% to 97% with a median of 89%. There was considerable variation in A&F interventions with 51% for individual providers only, 92% targeting behaviour change and 79% targeting processes of care, 64% performed by the provider group and 81% reporting aggregate patient data. CONCLUSIONS: Our process identified 17 A&F design elements, demonstrated gaps in reporting and helped understand the degree of variation in A&F interventions. PMID- 26811543 TI - Tubercular dactylitis. PMID- 26811544 TI - Phlegmasia cerulea dolens. PMID- 26811545 TI - RAF1 is increased in labouring myometrium and modulates inflammation-induced pro labour mediators. AB - Inflammation plays a central role in the terminal process of human labour and delivery, including myometrial contractions. RAF1 proto-oncogene serine/threonine protein kinase (RAF1) can activate ERK (official gene symbol MAPK1) and/or nuclear factor-kappa B (NF-kappaB) to regulate genes involved in inflammation. There are, however, no studies on the role of RAF1 in the processes of human labour and delivery. Thus, the aims of this study were to determine the effect of i) human labour and pro-inflammatory cytokines interleukin 1 beta (IL1B) and tumour necrosis factor (TNF) alpha on RAF1 protein expression in myometrium and ii) siRNA knockdown of RAF1 on pro-inflammatory and pro-labour mediators in human myometrial primary cells. Term labour was associated with an increase in RAF1 protein expression. Furthermore, RAF1 protein expression was increased in myometrial cells treated with IL1B and TNF, two likely factors contributing to preterm birth. Knockdown of RAF1 by siRNA in primary myometrial cells significantly decreased IL1B- and TNF-induced IL1A, IL1B, IL6, (C-X-C motif) ligand 8 (CXCL8)and chemokine (C-C motif) ligand 2 (CCL2) mRNA abundance and IL6, IL8 and CCL2; prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA levels and prostaglandin PGF2 alpha release; and NF-kappaB activation. Furthermore, RAF1 knockdown was associated with decreased activation of ERK in the presence of IL1B but not TNF. Concordantly, the ERK inhibitor U0126 significantly decreased IL1B induced IL6, CXCL8, CCL2 and PTGS2 mRNA abundance; IL6, CXCL8, CCL2 and PGF2 alpha release; and NF-kappaB activation. In conclusion, IL1B induces the expression and secretion of pro-labour mediators through the RAF1-MAPK1-NF-kappaB signalling pathway. TNF, on the other hand, regulates pro-labour mediators through the RAF1-NF-kappaB signalling pathway via an MAPK1-independent mechanism. PMID- 26811546 TI - Induced lipid peroxidation in ram sperm: semen profile, DNA fragmentation and antioxidant status. AB - Action of reactive oxygen species, protamination failures and apoptosis are considered the most important etiologies of sperm DNA fragmentation. This study evaluated the effects of induced lipid peroxidation susceptibility on native semen profile and identified the mechanisms involved in sperm DNA fragmentation and testicular antioxidant defense on Santa Ines ram sperm samples. Semen was collected from 12 adult rams (Ovis aries) performed weekly over a 9-week period. Sperm analysis (motility, mass motility, abnormalities, membrane and acrosome status, mitochondrial potential, DNA fragmentation, lipid peroxidation and intracellular free radicals production); protamine deficiency; PRM1, TNP1 and TNP2 gene expression; and determination of glutathione peroxidase (GPx), glutathione reductase, catalase (CAT) and superoxide dismutase activity and immunodetection in seminal plasma were performed. Samples were distributed into four groups according to the sperm susceptibility to lipid peroxidation after induction with ascorbate and ferrous sulfate (low, medium, high and very high). The results were analyzed by GLM test and post hoc least significant difference. We observed an increase in native GPx activity and CAT immunodetection in groups with high susceptibility to induced lipid peroxidation. We also found an increase in total sperm defects, acrosome and membrane damages in the group with the highest susceptibility to induced lipid peroxidation. Additionally, the low mitochondrial membrane potential, susceptible to chromatin fragmentation and the PRM1 mRNA were increased in the group showing higher susceptibility to lipid peroxidation. Ram sperm susceptibility to lipid peroxidation may compromise sperm quality and interfere with the oxidative homeostasis by oxidative stress, which may be the main cause of chromatin damage in ram sperm. PMID- 26811548 TI - Volunteering is associated with increased survival in able-bodied participants of the English Longitudinal Study of Ageing. AB - BACKGROUND: Volunteering has been linked to reduced mortality in older adults, but the mechanisms explaining this effect remain unclear. This study investigated whether volunteering is associated with increased survival in participants of the English Longitudinal Study of Ageing and whether differences in survival are modified by functional disabilities. METHODS: A multivariate Cox Proportional Hazards model was used to estimate the association of volunteering with survival over a period of 10.9 years in 10 324 participants, while controlling for selected confounders. To investigate effect modification by disability, the analyses were repeated in participants with and without self-reported functional disabilities. RESULTS: Volunteering was associated with a reduced probability of death from all causes in univariate analyses (HR=0.65, CI 0.58 to 0.73, p<0.0001), but adjustment for covariates rendered this association non significant (HR=0.90, CI 0.79 to 1.01, p=0.07). Able-bodied volunteers had significantly increased survival compared with able-bodied non-volunteers (HR=0.81, 95% CI 0.69 to 0.95, p=0.009). There was no significant survival advantage among disabled volunteers, compared with disabled non-volunteers (HR=1.06, CI 0.88 to 1.29, p=0.53). CONCLUSIONS: Volunteering is associated with reduced mortality in older adults in England, but this effect appears to be limited to volunteers who report no disabilities. PMID- 26811549 TI - Removal of Cu (II) and Pb (II) from Aqueous Solution using engineered Iron Oxide Nanoparticles. AB - Nano-sized Fe3O4 and Fe2O3 were synthesized using a precipitation method. The nanomaterials were tested as adsorbents for the removal of both Cu2+ and Pb2+ ions. The nanomaterials were characterized using X-ray powder diffraction to determine both the phase and the average grain size of the synthesized nanomaterials. Batch pH studies were performed to determine the optimum binding pH for both the Cu2+ and Pb2+ to the synthesized nanomaterials. The optimum binding was observed to occur at pH 4 and above. Time dependency studies for Cu2+ and Pb2+ showed the binding occurred within the first five minutes of contact and remained constant up to 2 hours of contact. Isotherm studies were utilized to determine the binding capacity of each of the nanomaterials for Cu2+ and Pb2+. The binding capacity of Fe3O4 with Cu2+ and Pb2+ were 37.04 mg/g and 166.67 mg/g, respectively. The binding capacities of the Fe2O3 nanomaterials with Cu2+ and Pb2+ were determined to be 19.61 mg/g and 47.62 mg/g, respectively. In addition, interference studies showed no significant reduction in the binding of either Cu2+ or Pb2+ to the Fe3O4 or Fe2O3 nanomaterials in the presence of solutions containing the individual ions Na+, K+, Mg2+ and Ca2+ or a solution consisting of a combination of all the aforementioned cations in one solution. PMID- 26811550 TI - Axillary ultrasound and fine-needle aspiration in preoperative staging of axillary lymph nodes in patients with invasive breast cancer. AB - OBJECTIVE: To propose an algorithm to determine the necessity for ultrasonography guided fine-needle aspiration (US-FNA) in preoperative axillary lymph node staging of patients with invasive breast cancer. MATERIALS AND METHODS: Prospective study developed at National Cancer Institute. The study sample included 100 female patients with breast cancer referred for axillary staging by US-FNA. RESULTS: The overall US-FNA sensitivity was set at 79.4%. The positive predictive value was calculated to be 100%, and the negative predictive value, 69.5%. The US-FNA sensitivity for lymph nodes with normal sonographic features was 0%, while for indeterminate lymph nodes it was 80% and, for suspicious lymph nodes, 90.5%. In the assessment of invasive breast tumors stages T1, T2 and T3, the sensitivity was respectively 69.6%, 83.7% and 100%. US-FNA could avoid sentinel node biopsy in 54% of cases. CONCLUSION: Axillary ultrasonography should be included in the preoperative staging of all patients with invasive breast cancer. The addition of US-FNA in cases of lymph nodes suspicious for malignancy may prevent more than 50% of sentinel lymphadenectomies, significantly shortening the time interval to definitive therapy. PMID- 26811551 TI - Retrospective study of sonographic findings in bone involvement associated with rotator cuff calcific tendinopathy: preliminary results of a case series. AB - OBJECTIVE: The present study was aimed at investigating bone involvement secondary to rotator cuff calcific tendonitis at ultrasonography. MATERIALS AND METHODS: Retrospective study of a case series. The authors reviewed shoulder ultrasonography reports of 141 patients diagnosed with rotator cuff calcific tendonitis, collected from the computer-based data records of their institution over a four-year period. Imaging findings were retrospectively and consensually analyzed by two experienced musculoskeletal radiologists looking for bone involvement associated with calcific tendonitis. Only the cases confirmed by computed tomography were considered for descriptive analysis. RESULTS: Sonographic findings of calcific tendinopathy with bone involvement were observed in 7/141 (~ 5%) patients (mean age, 50.9 years; age range, 42-58 years; 42% female). Cortical bone erosion adjacent to tendon calcification was the most common finding, observed in 7/7 cases. Signs of intraosseous migration were found in 3/7 cases, and subcortical cysts in 2/7 cases. The findings were confirmed by computed tomography. Calcifications associated with bone abnormalities showed no acoustic shadowing at ultrasonography, favoring the hypothesis of resorption phase of the disease. CONCLUSION: Preliminary results of the present study suggest that ultrasonography can identify bone abnormalities secondary to rotator cuff calcific tendinopathy, particularly the presence of cortical bone erosion. PMID- 26811552 TI - Anatomical variations of the celiac trunk and hepatic arterial system: an analysis using multidetector computed tomography angiography. AB - OBJECTIVE: To analyze the prevalence of anatomical variations of celiac arterial trunk (CAT) branches and hepatic arterial system (HAS), as well as the CAT diameter, length and distance to the superior mesenteric artery. MATERIALS AND METHODS: Retrospective, cross-sectional and predominantly descriptive study based on the analysis of multidetector computed tomography images of 60 patients. RESULTS: The celiac trunk anatomy was normal in 90% of cases. Hepatosplenic trunk was found in 8.3% of patients, and hepatogastric trunk in 1.7%. Variation of the HAS was observed in 21.7% of cases, including anomalous location of the right hepatic artery in 8.3% of cases, and of the left hepatic artery, in 5%. Also, cases of joint relocation of right and left hepatic arteries, and trifurcation of the proper hepatic artery were observed, respectively, in 3 (5%) and 2 (3.3%) patients. Mean length and caliber of the CAT were 2.3 cm and 0.8 cm, respectively. Mean distance between CAT and superior mesenteric artery was 1.2 cm (standard deviation = 4.08). A significant correlation was observed between CAT diameter and length, and CAT diameter and distance to superior mesenteric artery. CONCLUSION: The pattern of CAT variations and diameter corroborate the majority of the literature data. However, this does not happen in relation to the HAS. PMID- 26811553 TI - Monte Carlo derivation of filtered tungsten anode X-ray spectra for dose computation in digital mammography. AB - OBJECTIVE: Derive filtered tungsten X-ray spectra used in digital mammography systems by means of Monte Carlo simulations. MATERIALS AND METHODS: Filtered spectra for rhodium filter were obtained for tube potentials between 26 and 32 kV. The half-value layer (HVL) of simulated filtered spectra were compared with those obtained experimentally with a solid state detector Unfors model 8202031-H Xi R/F & MAM Detector Platinum and 8201023-C Xi Base unit Platinum Plus w mAs in a Hologic Selenia Dimensions system using a direct radiography mode. RESULTS: Calculated HVL values showed good agreement as compared with those obtained experimentally. The greatest relative difference between the Monte Carlo calculated HVL values and experimental HVL values was 4%. CONCLUSION: The results show that the filtered tungsten anode X-ray spectra and the EGSnrc Monte Carlo code can be used for mean glandular dose determination in mammography. PMID- 26811554 TI - Compressive neuropathy of the first branch of the lateral plantar nerve: a study by magnetic resonance imaging. AB - OBJECTIVE: To assess the prevalence of isolated findings of abnormalities leading to entrapment of the lateral plantar nerve and respective branches in patients complaining of chronic heel pain, whose magnetic resonance imaging exams have showed complete selective fatty atrophy of the abductor digiti quinti muscle. MATERIALS AND METHODS: Retrospective, analytical, and cross-sectional study. The authors selected magnetic resonance imaging of hindfoot of 90 patients with grade IV abductor digiti quinti muscle atrophy according to Goutallier and Bernageau classification. Patients presenting with minor degrees of fatty muscle degeneration (below grade IV) and those who had been operated on for nerve decompression were excluded. RESULTS: A female prevalence (78.8%) was observed, and a strong correlation was found between fatty muscle atrophy and plantar fasciitis in 21.2%, and ankle varices, in 16.8% of the patients. CONCLUSION: Fatty atrophy of the abductor digiti quinti muscle is strongly associated with neuropathic alterations of the first branch of the lateral plantar nerve. The present study showed a significant association between plantar fasciitis and ankle varices with grade IV atrophy of the abductor digiti quinti muscle. PMID- 26811555 TI - Chest magnetic resonance imaging: a protocol suggestion. AB - In the recent years, with the development of ultrafast sequences, magnetic resonance imaging (MRI) has been established as a valuable diagnostic modality in body imaging. Because of improvements in speed and image quality, MRI is now ready for routine clinical use also in the study of pulmonary diseases. The main advantage of MRI of the lungs is its unique combination of morphological and functional assessment in a single imaging session. In this article, the authors review most technical aspects and suggest a protocol for performing chest MRI. The authors also describe the three major clinical indications for MRI of the lungs: staging of lung tumors; evaluation of pulmonary vascular diseases; and investigation of pulmonary abnormalities in patients who should not be exposed to radiation. PMID- 26811557 TI - Aspiration pneumonia in children: an iconographic essay. AB - In most cases of aspiration pneumonia in children, the disease is specific to this age group. Clinical and radiological correlation is essential for the diagnosis. The present pictorial essay is aimed at showing typical images of the most common etiologies. PMID- 26811556 TI - Computed tomography angiography in patients with active gastrointestinal bleeding. AB - Gastrointestinal bleeding represents a common medical emergency, with considerable morbidity and mortality rates, and a prompt diagnosis is essential for a better prognosis. In such a context, endoscopy is the main diagnostic tool; however, in cases where the gastrointestinal hemorrhage is massive, the exact bleeding site might go undetected. In addition, a trained professional is not always present to perform the procedure. In an emergency setting, optical colonoscopy presents limitations connected with the absence of bowel preparation, so most of the small bowel cannot be assessed. Scintigraphy cannot accurately demonstrate the anatomic location of the bleeding and is not available at emergency settings. The use of capsule endoscopy is inappropriate in the acute setting, particularly in the emergency department at night, and is a highly expensive method. Digital angiography, despite its high sensitivity, is invasive, presents catheterization-related risks, in addition to its low availability at emergency settings. On the other hand, computed tomography angiography is fast, widely available and minimally invasive, emerging as a promising method in the diagnostic algorithm of these patients, being capable of determining the location and cause of bleeding with high accuracy. Based on a critical literature review and on their own experience, the authors propose a computed tomography angiography protocol to assess the patient with gastrointestinal bleeding. PMID- 26811558 TI - Mixed subtype of congenital mesoblastic nephroma with poor evolution: a case report and literature review. AB - A male child born at 27 weeks, weighting 1305 g and presenting with a right-sided abdominal tumor. Computed tomography scan demonstrated the presence of a solid mass compressing the right kidney. Puncture biopsy revealed congenital mesoblastic nephroma. The patient underwent total right nephroureterectomy, and died on the second day after surgery. PMID- 26811559 TI - Plantar vein thrombosis: a rare differential diagnosis in patients with plantar pain. PMID- 26811560 TI - Pulmonary neoplasia mimicking fungus ball. PMID- 26811561 TI - Extramedullary plasmacytoma in the right pulmonary hilum. PMID- 26811562 TI - PET/CT and brown fat in the evaluation of treatment response in Hodgkin lymphoma. PMID- 26811563 TI - Sonographic diagnosis of carpal tunnel syndrome. PMID- 26811565 TI - Identifying copepod functional groups from species functional traits. AB - We gathered information on the functional traits of the most representative copepod species in the Mediterranean Sea. Our database includes 191 species described by 7 traits encompassing diverse ecological functions: minimal and maximal body length, trophic group, feeding type, spawning strategy, diel vertical migration and vertical habitat. Cluster analysis in the functional trait space revealed that Mediterranean copepods can be separated into groups with distinct ecological roles. PMID- 26811564 TI - MRI of the chest: review of imaging strategies. PMID- 26811566 TI - Rapid Metal -free Macromolecular Coupling via in situ Nitrile Oxide-Activated Alkene Cycloaddition. AB - Nitrile oxide 1,3 dipolar cycloaddition is a simple and powerful coupling methodology. However, the self-dimerization of nitrile oxides has prevented the widespread use of this strategy for macromolecular coupling. By combining an in situ nitrile oxide generation with a highly reactive activated dipolarophile, we have overcome these obstacles and present a metal-free macromolecular coupling strategy for the modular synthesis of several ABA triblock copolymers. Nitrile oxides were generated in situ from chloroxime terminated poly(dimethylsiloxane) B blocks and coupled with several distinct hydrophilic (poly(2-methyloxazoline) and poly(ethylene glycol)), and poly(N-isopropylacrylamide) or hydrophobic (poly(L lactide) A-blocks terminated in activated dipolarophiles in a rapid fashion with high yield. This methodology overcomes many drawbacks of previously reported metal-free methods due to its rapid kinetics, versatility, scalability, and ease of introduction of necessary functionality. Nitrile oxide cycloaddition should find use as an attractive macromolecular coupling strategy for the synthesis of biocompatible polymeric nanostructures. PMID- 26811567 TI - Role of FNAC, fluid specimens, and cell blocks for cytological diagnosis of lung cancer in the present era. AB - Cytoblocks prepared from residual tissue fluids and fine-needle aspirations can be useful adjuncts to smears for establishing a more definitive cytopathologic diagnosis. These paraffin embedded cytoblocks have been popular since these can be handled like any other histologic specimen. Rapid on-site evaluation (ROSE) can help in attaining adequate material in the cytoblock, which is a major concern to the cytopathologists. Ancillary studies can be done using cytoblocks including IHC and various molecular techniques. The opportunities for cytopathologists to influence therapy, and uncover strategies in the complex field of lung cancer are exciting and limitless especially in the presence of an adequate cytoblock. PMID- 26811568 TI - Bax and Bak expression in cervical smears of women with low-and high-risk HPV types: A study of 120 cases. AB - BACKGROUND: Human papillomavirus (HPV) is known to be involved in the carcinogenesis of squamous cells in uterine cervix cancer, mostly by binding and inactivating the p53 and pRb tumor suppressor genes. Lately, evidence has emerged suggesting that HPV oncoproteins may interact with proteins involved in cellular apoptosis as well. AIM: This study aimed to investigate the expression of proapoptotic proteins Bax and Bak in women with low-risk and high-risk HPV types as opposed to HPV-negative women, and in women with normal pap smear compared to women with abnormal Papanicolau test (Pap) smear. MATERIALS AND METHODS: A total of 120 liquid-based cervical samples were subtyped for HPV types with microarray hybridization and then stained and evaluated immunocytochemically for Bax and Bak expression. Statistical analysis was performed on the Bax and Bak scores (percentage of positive cells * staining intensity), the overall percentage of positive cells, and the most prevalent staining intensity group found in each sample. RESULTS: A weak association between negative Bax staining and cytologically normal Pap smears was discovered, whereas cytologically abnormal samples tended to stain weakly or moderately positive. No other statistically significant difference was found in the other analyzed parameters. CONCLUSION: Cytologically normal pap smears seem to have a slight tendency to stain negative for Bax as opposed to cytologically abnormal pap smears. Although the association is weak, it is an indication that there might be a connection between the expression of Bax and the development of cervical intraepithelial dysplasia, which warrants further investigation in larger-scale studies. PMID- 26811569 TI - The utility of ROSE (rapid on-site evaluation) in endobronchial ultrasound (EBUS) guided transbronchial needle aspiration (TBNA): Is the picture rosy? AB - BACKGROUND: Mediastinal lymphadenopathy (ML) presents a diagnostic challenge. The technique to sample the lymph nodes has evolved from conventional "blind" transbronchial needle aspiration (TBNA) to the present day endobronchial ultrasound (EBUS)-guided procedure that improves the accuracy of sampling. OBJECTIVE: This study was undertaken to evaluate the utility of "rapid on-site evaluation" (ROSE) in EBUS-guided TBNA (EBUS-TBNA) for the diagnosis of ML. PATIENTS AND METHODS: This prospective study included 80 patients who underwent EBUS-TBNA for computed tomography/positron emission tomography (CT/PET) diagnosed ML over a 4-month period at a single tertiary care center. All 80 of these patients underwent histopathological evaluation (HPE) in addition to cytology. Three out of these 80 (3.7%) patients were excluded in view of inadequate material on EBUS-TBNA. After the sampling of nodes was done, the slides were stained with rapid hematoxylin and eosin (H&E) and then on-site evaluation was done. The tissue derived was also processed for HPE in all cases. RESULTS: ROSE revealed granuloma in 27 patients and malignancy in 14 patients, and the remaining patients showed nonspecific inflammation. Concomitant histopathology revealed granuloma in 34 patients and malignancy in 14 patients. Considering HPE as gold standard, the overall sensitivity and specificity of EBUS-TBNA for diagnosis were 85.4% and 89.6%, respectively. For malignancy alone, the sensitivity and specificity were 100% and 98.4%, respectively. CONCLUSION: This novel approach is safe, has good diagnostic yield, and has an excellent potential in assisting safe and accurate diagnostic interventional bronchoscope. PMID- 26811570 TI - Cytopathological diagnosis of gallbladder mass and mural thickening based on imaging findings: A prospective study of 51 cases. AB - BACKGROUND: Image-guided fine-needle aspiration cytology (FNAC) serves as first line diagnostic modalities for the assessment of mural thickening of the gallbladder (GB). AIM: The main objective of the present study was to correlate the diagnostic accuracy of preoperative image-guided FNAC of the thickened GB wall based on imaging findings to arrive at a final diagnosis in a tertiary care center. MATERIALS AND METHODS: Fifty-seven image-guided fine-needle aspirations (FNAs) were performed from mural thickening of the GB over a period of 4 years and the smears prepared were stained with Leishman and Papanicolaou (Pap) stain. Out of 57 cases, 51 were included in the study for which follow-up histopathology was performed. RESULT: Out of 51 aspirations, 43 (84.3%) were adequate, 5 (9.8%) were inconclusive, and 3 (5.9%) were inadequate. Among the adequate aspirations, the most common was adenocarcinoma-36 (70.5%). The correlation between confirmatory cytological diagnosis and adequacy was significantly high (P = 0.0001). The overall diagnostic accuracy for adequate aspiration was 95.3%. The common diagnostic pitfalls were necrotic areas, aspiration of reactive hepatocytes adjacent to the GB mass, and mucus islands. No procedural complication was observed in any patient. CONCLUSIONS: Image-guided FNAC can be used as a safe, rapid, and successful diagnostic procedure with high sensitivity, specifically for supporting and confirming ultrasonography(USG)/computed tomography (CT) diagnosis of GB mass or mural thickening of the wall. PMID- 26811571 TI - FNAC accuracy in diagnosis of thyroid neoplasms considering all diagnostic categories of the Bethesda reporting system: A single-institute experience. AB - BACKGROUND: Thyroid fine-needle aspiration cytology (FNAC) is a valuable test used for diagnosing diseases of the thyroid gland. AIMS: Using all satisfactory categories of the Bethesda system, this study aimed to determine the accuracy with which FNAC diagnoses thyroid neoplasms. We also discuss the factors that affect diagnosis accuracy. SETTINGS AND DESIGN: A comparison was drawn between FNAC results and final histological diagnosis using samples collected over a period of 3 years. MATERIALS AND METHODS: For all patients, age, sex, cytological features, and histological types were determined. All cases of false negative (FN) and false positive (FP) diagnosis were reanalyzed. STATISTICAL ANALYSIS USED: The chi-square test and univariate analysis were performed to examine the relationship between different variables. RESULTS: About 52% of the cases were found malignant, and they were of six different histological types. Papillary carcinoma was the commonest type of malignancy at 76.9%. The rate of malignancy was 63% in males and 49.4% in females. In two of the FN cases, the tumor had a diameter of >=35 mm. Of the 12 FP cases, nine were in the follicular neoplasm or suspicious for follicular neoplasm Bethesda category. FNAC diagnosis had 95.2% sensitivity, 68.4% specificity, 83.3% positive predictive value, 89.6% negative predictive value, and 85.14% accuracy. CONCLUSIONS: FNAC was found to have a high level of sensitivity and an acceptable degree of specificity in diagnosing different types of thyroid neoplasms. The presence of microfollicular structures or crowded cellular clusters is a challenge to diagnosis, particularly in low quality specimens. PMID- 26811572 TI - Langerhans cell histiocytosis in children diagnosed by fine-needle aspiration. AB - BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare intricate pediatric neoplasm with varied clinical manifestations and multiple treatment modalities. AIM: To study the cytological features of LCH and the differential diagnoses on fine-needle aspiration (FNA). MATERIALS AND METHODS: FNA was performed using a 23 gauge needle fitted to a 10 mL syringe mounted on syringe holder. LCH was diagnosed on FNA smears in seven cases confined to the head and neck region, which included three cases of lymphadenopathy, three cases of scalp swelling, and one case of orbital swelling. RESULTS: The age of the patients ranged from 25 days to 11 years and male-to-female ratio was 1:1.3. Clinically, the diagnoses suggested were tuberculosis, inflammatory lesion, abscess, and malignancy. The cytologic findings included high cellularity, isolated Langerhans cells (LCs) with prominent nuclear indentation, grooves and abundant vacuolated cytoplasm, multinucleated giant cells, eosinophils, and lymphocytes. Areas of necrosis were noted in one case. Histopathology, along with positive S-100 immunohistochemistry, confirmed the diagnosis of LCH. CONCLUSIONS: LCH is a rare disease occurring predominantly in children and can be diagnosed with ease on FNA cytology by the presence of characteristic Langerhans cells. The S-100 positivity aids in suggesting a diagnosis of LCH. PMID- 26811573 TI - Optimization of FNAC findings as a preoperative diagnostic aid for odontogenic cysts. AB - BACKGROUND: Fine-needle aspiration cytology (FNAC) is not a definitive preoperative diagnostic procedure done for all cases of odontogenic cysts. This is because of the inconsistent results obtained with it. AIMS: This study was done to optimize FNAC findings and help in preoperative characterization of odontogenic cysts. MATERIALS AND METHODS: Cystic fluid was collected and centrifuged from 50 odontogenic cysts that were planned for excision. Three smears were prepared from the cell sediment obtained after centrifugation and stained. The stained sections were examined for presence and type of epithelial cells, to formulate a preopererative diagnosis. RESULTS: Epithelial cells were detected in 46% cases in smear 1, 48% cases in smear 2, and 52% cases in smear 3. When all three smears from one case were studied, 86% cases showed epithelial cells for evaluation. CONCLUSION: Cystic aspirate should be centrifuged and the entire cell sediment should be examined by making multiple smears for evaluation of cystic epithelial lining cells. PMID- 26811574 TI - Comparative cytomorphometric analysis of oral mucosal cells in normal, tobacco users, oral leukoplakia and oral squamous cell carcinoma. AB - BACKGROUND: Squamous cell carcinoma (SCC) is the third most common cause of oral morbidity in India despite the numerous advances made in the treatment protocol. AIM: To compare the cytomorphometric changes of oral mucosal cells in normal subjects (Group I) with that of tobacco users without any lesion (Group II), tobacco users with oral leukoplakia (Group III), and tobacco users with oral SCC (Group IV) through a semi-automated image analysis system. MATERIALS AND METHODS: Oral mucosal cells collected from study subjects (n = 100) stained using rapid Papanicolaou stain. Photomicrograph of 50 nonoverlapping cells captured at 50* magnification with a digital image capture system. Cytomorphometric analysis of cells in the captured images was performed with Image-Pro image analysis software. Image analysis was performed to obtain cell diameter (CD), cytoplasmic area (CyA), nuclear diameter (ND), nuclear area (NA), and nuclear-to-cytoplasmic ratio. These values were statistically compared among the groups using one-way analysis of variance (ANOVA) and Mann-Whitney U test. RESULTS: The ND, NA, and nuclear-to-cytoplasmic ratio values were found to be increased in the samples collected from leukoplakia and oral SCC. The CD and CyA decreased compared to the normal mucosa in oral SCC samples. CONCLUSION: The cytomorphometric changes observed in samples from oral SCC and oral leukoplakia were consistent with the current diagnostic features. Hence, the semi-automated cytomorphometric analysis of oral mucosal cells can be used as an objective adjunct diagnostic tool in the diagnosis of these lesions. PMID- 26811575 TI - Conjunctival impression cytology versus routine tear function tests for dry eye evaluation in contact lens wearers. AB - AIMS: Prolonged contact lens wear is often accompanied by dryness of the eyes. The aim of this study was to compare conjunctival impression cytology (CIC) and tear film tests such as tear film break up time (TBUT) and Schirmer test for dry eye evaluation in contact lens wearers and measure their correlation with dry eye symptoms. SETTING: A case control study was done at three referral eye centers. MATERIALS AND METHODS: The eyes of 230 contact lens users were compared to 250 eyes of age- and sex-matched controls. Participants were recruited based on their response to a questionnaire of dry eye symptoms, (Dry Eye Scoring System, DESS((c))) and measurements of TBUT, Schirmer test, and CIC was done. A correlation analysis between symptom severity and tear film tests was performed. Pearson's coefficient, R(2) > 0.5 was considered significant. RESULTS: As compared to controls (r (2) = 0.010), Nelson grade correlated significantly with dry eye symptoms (r (2) = 0.765), among cases. However, there was moderate correlation between dry eye symptoms, Schirmer test, and TBUT (r (2) = 0.557 and 0.530, respectively) among cases and a weak correlation among controls (r (2) = 0.130 and 0.054, respectively). The sensitivity of TBUT was 86.4%, specificity was 82.4%, positive likelihood ratio (LR) was 4.50 [95% confidence interval (CI) 3.46-5.85)], and negative LR was 0.09. The sensitivity of the Schirmer test was 48.2%, specificity 88%, LR 2.12 (95% CI 1.48-2.96), and negative LR 0.83. CONCLUSION: CIC correlates better than Schirmer and TBUT with dry eye symptoms. It may be the most appropriate test for dry-eye evaluation in contact lens wearers. PMID- 26811576 TI - "Sea anemone-like ciliated tumor cells" in a case of serous cystadenocarcinoma of the ovary. PMID- 26811577 TI - Cytodiagnosis of isolated primary hydatid cyst of breast masquerading as a breast neoplasm: A rare case report. AB - Hydatid cyst in the breast is very rare and unusual for its location. Reported incidence of hydatid cyst in the breast is 0.27% in the literature. Herein, we report a case of hydatid cyst of breast in a 65-year-old female who presented with painless, slowly growing lump in the breast mimicking breast neoplasm clinically. Radiological investigations such as ultrasonography and mammography may be helpful but not conclusive. Preoperative fine-needle aspiration cytology (FNAC) diagnosis was consistent with hydatid cyst of breast and was without any complications. Histopathological examination of lumpectomy specimen confirmed the diagnosis of hydatid cyst of breast. High suspicion of this entity should be there in the differential diagnosis in the evaluation of breast lump in endemic as well as in migrant population in nonendemic areas. PMID- 26811579 TI - Metastatic cervical carcinoma masquerading as iliopsoas abscess in an HIV negative woman-diagnosed on fine-needle aspiration cytology: A case report. AB - The most common pathology in iliopsoas region in the Indian subcontinent is tuberculosis. The iliopsoas compartment can also be affected by other conditions such as hemorrhage and tumors. However, isolated metastasis in the area is usually rare, especially in cases where the primary malignancy is undiagnosed previously. Such cases may be misinterpreted on radiological examination as psoas abscess of infectious origin. Here we present a case of metastasis in psoas muscle from a previously undiagnosed case of carcinoma cervix. PMID- 26811578 TI - Fine needle aspiration cytology of vulvar actinomycosis masquerading clinically as malignancy. AB - Actinomycosis is a chronic infection caused by Actinomyces israelii, usually seen in immunocompromised patients or in the background of tissue injury. Vulvar actinomycosis presenting as a fixed swelling in an elderly individual can mimic malignancy and pose a diagnostic dilemma. We report here a case of vulvar actinomycosis diagnosed by fine needle aspiration (FNA). A 60-year-old postmenopausal female presented with a gradually increasing 15 cm * 10 cm vulvar swelling involving the right mons and right labia majora. The swelling was nodular, fixed, and nonulcerated, with multiple healed and few active discharging sinus tracts draining serosanguineous fluid and yellowish sulfur granules. FNA was diagnostic, as it revealed colonies of Actinomyces surrounded by polymorphs. Histopathology of excised specimen confirmed the cytological findings. FNA is an effective tool in the diagnosis of actinomycosis, although, its documentation is rare. Difficulties in the management can be avoided by early diagnosis using the FNA technique. PMID- 26811580 TI - A case of papillary microcarcinoma of the thyroid with abundant colloid (masquerading as colloid goiter with papillary hyperplasia): Cytological evaluation with histopathological correlation. AB - Papillary thyroid carcinoma (PTC) is the most common malignant neoplasm of the thyroid. On fine-needle aspiration (FNA) cytology smears of conventional PTC, the background usually shows scanty, bubble gum-like colloid. But the macrofollicular variant and papillary microcarcinoma reveals abundant thin colloid in the background. We report a case of papillary carcinoma of thyroid in a 37-year-old female with abundant thin colloid, obscuring the nuclear morphology in many clusters, along with the presence of typical nuclear features within occasional clusters in FNA cytology and hence, masquerading as colloid goiter with papillary hyperplasia. Histopathological examination of the total thyroidectomy specimen revealed papillary microcarcinomatous focus in a background of nodular hyperplasia. The differential diagnosis of PTC should be entertained even in colloid-rich FNA smears if the typical nuclear features are present. Hence, a meticulous search for any fragment with nuclear features of PTC is mandatory before labeling the smears as benign nodular hyperplasia. PMID- 26811581 TI - Bilaterally enlarged parotids and sicca symptoms as a presentation of sarcoidosis: Pivotal role of aspiration cytology in diagnosis. AB - Sarcoidosis is a chronic multisystem inflammatory disease of unknown etiology characterized by widespread noncaseating granulomas in various organs. The diagnosis of sarcoidosis is based on cytological, clinicolaboratory, and radiological findings, and requires careful exclusion of other granulomatous diseases especially tuberculosis. Involvement of parotid glands is uncommon. Presentation of sarcoidosis with sicca symptoms that include dryness of eyes and mouth is an even rarer phenomenon. We present a case of multisystemic sarcoidosis presenting with dryness of eyes and mouth along with bilateral enlargement of parotid glands. Fine-needle aspiration cytology (FNAC) smears showed epithelioid cell granulomas and multinucleate giant cells. Stain for acid-fast bacilli was negative. Careful cytological examination revealed crystalline structures inside the giant cells, which prompted us to evaluate the patient for sarcoidosis. This case report highlights the cytological features that can be useful in clinching the diagnosis of sarcoidosis in conjunction with clinicoradiological and laboratory findings in a clinically unusual case. PMID- 26811582 TI - Fine-needle aspiration cytology of ovarian steroid cell tumor: A rare case report. AB - Steroid cell tumors (SCTs) of the ovary are a rare subgroup of sex cord tumors that account for less than 0.1% of all ovarian tumors. These tumors can produce steroids, especially testosterone, which produces symptoms such as hirsutism, amenorrhea/oligomenorrhea, and male patterned voice. For evaluation of the androgen excess, testosterone and dehydroepiandrosterone sulfate (DHEA-S) are the first laboratory tests to be measured. Abdominal ultrasound and magnetic resonance imaging (MRI) are useful radiologic imaging techniques. Although SCTs are generally benign, the risk of malignant transformation is always present. Surgical excision of tumor is the most important and hallmark treatment. The present case signifies the early preoperative diagnosis of a virilizing SCT, based on cytological features and its careful correlation with clinicopathological and radiological findings. PMID- 26811583 TI - Lymphangioleiomyomatosis diagnosed by effusion cytology: A case report. AB - Lymphangioleiomyomatosis (LAM) is a rare lung disease traditionally affecting women during their childbearing years. It can be sporadic or be associated with tuberous sclerosis syndrome. It is usually manifested in the lungs, kidneys, and/or lymphatic system. It consists of an overgrowth of abnormal smooth muscle like cells, usually along the bronchovascular structures, resulting in the formation of cysts and the destruction of the lung parenchyma. We present the case of a 43-year-old woman with a history of pleural effusion and dyspnea. A computed tomographic scan revealed a mediastinal mass, chylothorax, and multiple pulmonary cysts. A diagnosis of LAM was rendered on a pleural fluid sample. PMID- 26811584 TI - Custom made filter card for cytospin: A high fidelity economical alternative. PMID- 26811585 TI - Use of cell block preparation for improving adequacy of cytology smears. PMID- 26811586 TI - Adjuvant hormonal therapy in premenopausal women with breast cancer. PMID- 26811587 TI - HPV vaccine: One, two, or three doses for cervical cancer prevention? PMID- 26811588 TI - Breast cancer screening existence in India: A nonexisting reality. PMID- 26811589 TI - Current scenario and efforts to propound equal and affordable global cancer surgery. PMID- 26811590 TI - Emergence of micronuclei as a genomic biomarker. AB - The presence of micronuclei (MN) in mammalian cells is related to several mutagenetic stresses. MN are formed as a result of chromosome damage and can be readily identified in exfoliated epithelial cells. MN is chromatin particles derived from acentric chromosomal fragments, which are not incorporated into the daughter nucleus after mitosis. It can be visualized by chromatin stains. A variety of factors influences the formation of MN in cells such as age, sex, genetic constitution, physical and chemical agents, adverse habits such as tobacco, areca nut chewing, smoking, and alcohol consumption. Micronucleation has important implications in the genomic plasticity of tumor cells. The present paper reviews the origin, fate and scoring criteria of MN that serves as a biomarker of exposure to genetic toxins, and for the risk of cancer. PMID- 26811591 TI - Emerging role of S-1 in gastric cancer. AB - Gastric cancer remains one of the most important malignancies worldwide in terms of incidence and mortality. The treatment is based on the combination of local surgery and radiation therapy as well as systemic chemotherapy and targeted molecules. Fluoropyrimidines and particularly 5-fluorouracil (FU) represent still the backbone for gastric cancer chemotherapy and new molecular versions of this molecule have been brought to clinical practice in order to improve benefits and reduce adverse effects. S-1 is an oral prodrug of 5-FU, which has demonstrated high effectiveness for gastric cancer treatment and a favorable safety profile. Currently, there are geographic differences in the treatment of gastric cancer and in the use of S-1, which is a mainstay of gastric cancer management in Eastern countries, but is not part of the standard care in the rest of the world. In this review, we gathered data from phase I, II, and III trials of S-1 in gastric cancer, in order to define its real benefit-risk ratio and assess whether geographic differences in S-1 use are justified by unchangeable factors. PMID- 26811592 TI - Therapeutic approach beyond conventional temozolomide for newly diagnosed glioblastoma: Review of the present evidence and future direction. AB - Glioblastoma multiforme (GBM) is the most aggressive form of primary brain tumor. Maximal safe surgical resection followed by adjuvant partial brain radiation with concurrent and adjuvant temozolomide (TMZ) (oral alkylating agent) is the standard of care. Five years survival in TMZ treated patient reaches 9.8%. We aimed to summarize the changes in the management of GBM beyond conventional temozolomide based adjuvant treatment. We searched the PUBMED with the following key words: Glioblastoma, phase III trial, Phase II trial, adjuvant treatment in GBM. Clinical research has found a wide range of molecular aberrations in GBM and attempts are being made to further improve survival with the addition of different classes of drugs. Angiogenesis inhibitors, oncolytic vaccines, dose dense TMZ, and anti-epidermal growth factor receptor monoclonal antibody in phase III trials have failed to improve survival. Recent studies have also shown that the management strategies might be different and needs to be customized as per the age of patients such as pediatric and elderly patients. In addition, treatments should be personalized depending on the molecular aberrations. We reviewed all published phase III trials for newly diagnosed GBM as well as also looked into possible future directions in this review. Limited progress has happed beyond conventional TMZ in the adjuvant treatment of GBM. Newer insights are emerging about treatment intensification and introduction of newer molecular targeted drugs with more information about molecular aberrations. PMID- 26811593 TI - Maintenance pemetrexed in nonsmall cell lung carcinoma: Outcome analysis from a tertiary care center. AB - BACKGROUND: Maintenance pemetrexed is a standard treatment option for selected non squamous nonsmall cell lung carcinoma patients having a response to platin based doublet. We conducted a clinical audit of such selected patients and report the outcome among the Indian population. AIM: To evaluate the outcomes with maintenance pemetrexed in the patients with locally advanced and metastatic adenocarcinoma lung. OBJECTIVES: To calculate the progression free survival (PFS), overall survival (OS), and factors affecting the outcome. MATERIALS AND METHODS: Data of patients with locally advanced and metastatic adenocarcinoma lung were retrieved from prospectively maintained lung cancer database registered between June 2011 and March 2014. The patients who achieved partial response (n = 87) or stable disease (n = 101) after 6 cycles of pemetrexed platin based doublet and received the maintenance pemetrexed were selected for final analysis (n = 188). Kaplan-Meir survival analysis was used for PFS and OS. Log rank test was used to evaluate the factors affecting the outcome. RESULTS: Median follow-up is 14 months. The median number of maintenance pemetrexed cycles received is 6 (1 38). Common reason for the discontinuation are disease progression (n = 127), renal toxicity (n = 4), and social/financial (n = 7). Median PFS and OS are 8 months and 20 months, respectively. The patients with baseline pleural effusion had better PFS (9 months vs. 7 months, P = 0.02) and OS (26 months vs. 18 months, P = 0.05). The patients receiving more than 6 cycles of maintenance had improved PFS (12 vs. 7 months, P = 0.002) and OS (26 vs. 16 months, P = 0.05). CONCLUSION: Maintenance pemetrexed is feasible and well tolerated by the majority of Indian patients who achieved the response after platin based doublet. The patients with baseline pleural effusion benefit more with maintenance pemetrexed. PMID- 26811594 TI - N-acetylcysteine renoprotection in methotrexate induced nephrotoxicity and its effects on B-cell lymphoma. AB - BACKGROUND: Nephrotoxicity is one of the known side effects of methotrexate (MTX) therapy despite the use of conventional protective measures. Our objectives were to evaluate the effects of N-acetylcysteine (NAC) on MTX-induced toxicity in renal tubular cells and to evaluate whether adjunctive use of NAC interferes with MTX antitumor activity in the B-cell lymphoma. METHODS: Kidney Epithelial (Madin Darby canine kidney [MDCK]) cells were exposed to MTX (10 MUM or 100 MUM) alone and with NAC (0.2 mM or 0.4 mM). Reactive oxygen species (ROS) generation at 1, 2, 4, and 24 h was measured by flow cytometer. Quantification of total glutathione (GSH) was performed by using GSH assay kit. To measure the impact of NAC on the antitumor activity of MTX, B lymphoma cells were exposed to MTX alone and with NAC. A percentage of apoptosis was measured using fluorescein isothiocyanate in both cell lines. Quantitative data was presented as a means +/- standard deviation, and P values were analyzed using the Student's t-test. RESULTS: Apoptosis in MDCK cells were observed after 24 h of incubation with both 10 MUM and 100 MUM MTX. Maximum ROS generation was observed at 4 h and corresponded to GSH production. Treatment with 0.2 and 0.4 mM of NAC led to decrease percentages of apoptotic MDCK cells. NAC did not change either proliferation or apoptosis of B-cell lymphoma. CONCLUSION: Using NAC for kidney protection may not interfere with the antitumor activity of MTX. Further in vivo studies are warranted to confirm noninterference between MTX and NAC and assess synergistic antitumor effects. PMID- 26811595 TI - Comparison of postoperative complications in advanced head and neck cancer patients receiving neoadjuvant chemotherapy followed by surgery versus surgery alone. AB - BACKGROUND: Head and neck cancer is the third most common cancer in India with 60% presenting in advanced stages. There is the emerging role of neoadjuvant chemotherapy (NACT) in the management of these advanced cancers. There is a general perception that complication rates are higher with the use of NACT. MATERIALS AND METHODS: This is a retrospectively collected data of head and neck cancer patients operated at our hospital from March 2013 to September 2014. A total of 205 patients were included in the study. These patients were studied in two groups. Group 1 included 153 patients who underwent surgery alone, and Group 2 included 52 patients who received 2-3 cycles of NACT followed by surgery. RESULTS: The mean age of the population was 51 years in the Group 1 and 45 years in Group 2. The hospital stay and readmissions in postoperative period were similar in the two groups. In this study, the complication rate was 37.9% in the surgery patients and 30.8% in the NACT patients (P = 0.424). CONCLUSION: The postoperative complication rates in patients who received NACT followed by surgery were not significantly different from those who underwent surgery. PMID- 26811596 TI - Clinical profile and outcome of adult Hodgkin lymphoma: Experience from a tertiary care institution. AB - Treatment and outcome of Hodgkin lymphoma (HL) are the true success story of modern medicine. The data from the developing countries on long-term outcome of patients with HL is sparse. AIMS: Primary objective is to assess the progression free survival (PFS). Secondary objective are overall survival (OS) and toxicities. SETTINGS AND DESIGN: This is a retrospective analysis from the case records from a single institution. MATERIALS AND METHODS: Institutional Ethical Committee approval was obtained. Between January 1991 and December 2010, 301 patients (age >=18 years) underwent treatment at our institution. STATISTICAL ANALYSIS: Kaplan-Meyer curves were used to calculate the PFS and OS. RESULTS: The median age at presentation was 36 years, range from 19 to 75 years. The male to female ratio was 2.9:1. Seventy-five percent of patients had B symptoms. Majority presented in advanced stage (Stage III and IV) disease (64.7%). Mixed cellularity (74.4%) was the most common histology, followed by nodular sclerosis (13.9%). The most common chemotherapy regimen used was ABVD (61%). CONCLUSIONS: Median follow up of the cohort was 18.5 months (range 2-225). PFS and OS rate at 5 years is 66.3% and 79.7% respectively. PMID- 26811597 TI - Acute lymphoblastic leukemia: A single center experience with Berlin, Frankfurt, and Munster-95 protocol. AB - BACKGROUND: There is a paucity of data on the outcome following the treatment for acute lymphoblastic leukemia (ALL) from developing countries. MATERIALS AND METHODS: Two hundred and thirty-eight consecutive patients with ALL <30 years of age diagnosed between January 2005 and December 2011 were analyzed retrospectively. Patients were treated modified Berlin, Frankfurt, and Munster 95 protocol. Event-free survival (EFS) was calculated using Kaplan-Meier survival analysis and variables were compared using log-rank test. RESULTS: The EFS was 63.4% at a median follow-up was 32.7 months. On univariate analysis National Cancer Institute (NCI) risk stratification, sex, white blood cell count, day 8 blast clearance, and income were significantly associated with EFS. However, on multivariate analysis only female sex (P = 0.01) and day 8 blast clearance (P = 0.006) were significantly associated with EFS. Seventy-four of 238 (31%) patients had recurrent leukemia. The common sites of relapse were bone marrow in 55/74 (75%) patients and central nervous system in 11/74 (20%) patients. CONCLUSION: Compared to western data, there was an increased proportion of NCI high-risk patients and T-cell immunophenotype in our study. There has been an improvement in outcome of patients with ALL at our center over the last 2 decades. Female sex and clearance of blast in peripheral blood by day 8 of induction was associated with better EFS. PMID- 26811598 TI - Clinical implication of thiopurine methyltransferase polymorphism in children with acute lymphoblastic leukemia: A preliminary Egyptian study. AB - BACKGROUND: 6-mercaptopurine (6-MP) is an essential component of pediatric acute lymphoblastic leukemia (ALL) maintenance therapy. Individual variability in this drug-related toxicity could be attributed in part to genetic polymorphism thiopurine methyltransferase (TPMT). AIM: To investigate the frequency of common TPMT polymorphisms in a cohort of Egyptian children with ALL and the possible relation between these polymorphisms and 6-MP with short-term complications. MATERIALS AND METHODS: This study included 25 children. Data related to 6-MP toxicity during the maintenance phase were collected from the patients' files. DNA was isolated and genotyping for TPMT G460A, and A719G mutations were performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Twenty (80%) of the included 25 patients had a polymorphic TPMT allele. TPMT*3A was the most frequent (14/25, 56%), 8 patients were homozygous and 6 were heterozygous. TPMT*3C mutant allele was found in 4 patients (16%) in the heterozygous state while 2 patients (8%) were found to be heterozygous for TPMT*3B mutant allele. TPMT mutant patients, especially homozygous, were at greater risk of 6-MP hematological toxicity without significant difference regarding hepatic toxicity. CONCLUSIONS: TPMT polymorphism was common among the studied group and was associated with increased risk of drug toxicity. A population-based multi-center study is required to confirm our results. PMID- 26811599 TI - Malignant gastric teratoma in a 3-month-old infant. PMID- 26811600 TI - Complete radiotherapy response in rectal cancer: A review of the evidence. AB - Complete response to chemoradiotherapy for rectal cancer is becoming a common clinical entity. Techniques to diagnose complete response and how to survey these patients without operative intervention are still unclear. We review the most recent evidence. Barriers to firm conclusions regarding this are heterogeneity of diagnostic definitions, differing surveillance protocols, and a lack of randomised studies. PMID- 26811601 TI - Targeted therapies in gastric cancer and future perspectives. AB - Advanced gastric cancer (AGC) is associated with a high mortality rate and, despite multiple new chemotherapy options, the survival rates of patients with AGC remains poor. After the discovery of targeted therapies, research has focused on the new treatment options for AGC. In the last two decades, many targeted molecules were developed against AGC. Currently, two targeted therapy molecules have been approved for patients with AGC. In 2010, trastuzumab was the first molecule shown to improve survival in patients with HER2-positive AGC as part of a first-line combination regimen. In 2014, ramucirumab was the second targeted molecule to improve survival rates and was suggested as treatment for patients with AGC who had progressed after first-line platinum plus fluoropyrimidine with or without anthracycline chemotherapy. Ramucirumab was the first targeted therapy acting as a single agent in patients with advanced gastroesophageal cancers. Although these two molecules were introduced into clinical use, many other promising molecules have been tested in phase I-II trials. It is obvious that in the near future many different targeted therapies will be in use for treatment of AGC. In this review, the current status of targeted therapies in the treatment of AGC and gastroesophageal junction tumors, including HER (2-3) inhibitors, epidermal growth factor receptor inhibitors, tyrosine kinase inhibitors, antiangiogenic agents, c-MET inhibitors, mammalian target of rapamycin inhibitors, agents against other molecular pathways fibroblast growth factor, Claudins, insulin-like growth factor, heat shock proteins, and immunotherapy, will be discussed. PMID- 26811602 TI - Tropomyosin-related kinase B/brain derived-neurotrophic factor signaling pathway as a potential therapeutic target for colorectal cancer. AB - Colorectal cancer (CRC) is the second most common cause of cancer-related death in western countries. Approximately one-quarter of newly diagnosed patients for CRC have metastases, and a further 40%-50% experience disease recurrence or develop metastases after all standard therapies. Therefore, understanding the molecular mechanisms involved in the progression of CRC and subsequently developing novel therapeutic targets is crucial to improve management of CRC and patients' long-term survival. Several tyrosine kinase receptors have been implicated in CRC development, progression and metastasis, including epidermal growth factor receptor (EGFR) and vascular EGFR. Recently, tropomyosin-related kinase B (TrkB), a tyrosine kinase receptor, has been reported in CRC and found to clearly exert several biological and clinical features, such as tumor cell growth and survival in vitro and in vivo, metastasis formation and poor prognosis. Here we review the significance of TrkB and its ligand brain derived neurotrophic factor in CRC. We focus on their expression in CRC tumor samples, and their functional roles in CRC cell lines and in in vivo models. Finally we discuss therapeutic approaches that can lead to the development of novel therapeutic agents for treating TrkB-expressing CRC tumors. PMID- 26811604 TI - Adjuvant chemotherapy for resected colorectal cancer metastases: Literature review and meta-analysis. AB - Surgical resection is the only option of cure for patients with metastatic colorectal cancer (CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy after surgical resection of CRC metastases despite the lower level of evidence (based on the quality of studies in this setting). However, there is still no standard treatment and the effective role of an adjuvant therapy remains controversial. The aim of this review is to report the state-of-art of systemic chemotherapy and regional chemotherapy with hepatic arterial infusion in the management of patients after resection of metastases from CRC, with a literature review and meta-analysis of the relevant randomized controlled trials. PMID- 26811605 TI - Integration of genome scale data for identifying new players in colorectal cancer. AB - Colorectal cancers (CRCs) display a wide variety of genomic aberrations that may be either causally linked to their development and progression, or might serve as biomarkers for their presence. Recent advances in rapid high-throughput genetic and genomic analysis have helped to identify a plethora of alterations that can potentially serve as new cancer biomarkers, and thus help to improve CRC diagnosis, prognosis, and treatment. Each distinct data type (copy number variations, gene and microRNAs expression, CpG island methylation) provides an investigator with a different, partially independent, and complementary view of the entire genome. However, elucidation of gene function will require more information than can be provided by analyzing a single type of data. The integration of knowledge obtained from different sources is becoming increasingly essential for obtaining an interdisciplinary view of large amounts of information, and also for cross-validating experimental results. The integration of numerous types of genetic and genomic data derived from public sources, and via the use of ad-hoc bioinformatics tools and statistical methods facilitates the discovery and validation of novel, informative biomarkers. This combinatory approach will also enable researchers to more accurately and comprehensively understand the associations between different biologic pathways, mechanisms, and phenomena, and gain new insights into the etiology of CRC. PMID- 26811606 TI - Dealing with robot-assisted surgery for rectal cancer: Current status and perspectives. AB - The laparoscopic approach for treatment of rectal cancer has been proven feasible and oncologically safe, and is able to offer better short-term outcomes than traditional open procedures, mainly in terms of reduced length of hospital stay and time to return to working activity. In spite of this, the laparoscopic technique is usually practised only in high-volume experienced centres, mainly because it requires a prolonged and demanding learning curve. It has been estimated that over 50 operations are required for an experienced colorectal surgeon to achieve proficiency with this technique. Robotic surgery enables the surgeon to perform minimally invasive operations with better vision and more intuitive and precise control of the operating instruments, thus promising to overcome some of the technical difficulties associated with standard laparoscopy. It has high-definition three-dimensional vision, it translates the surgeon's hand movements into precise movements of the instruments inside the patient, the camera is held and moved by the first surgeon, and a fourth robotic arm is available as a fixed retractor. The aim of this review is to summarise the current data on clinical and oncologic outcomes of robot-assisted surgery in rectal cancer, focusing on short- and long-term results, and providing original data from the authors' centre. PMID- 26811603 TI - Gut microbiota imbalance and colorectal cancer. AB - The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes (e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial-derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies. PMID- 26811607 TI - Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer. AB - The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum (F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6% (44/511), which was lower than that in United States cohort studies (13%). Similar to the United States studies, F. nucleatum positivity in Japanese colorectal cancers was significantly associated with microsatellite instability (MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets (i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain microRNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. MicroRNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in colorectal cancer cells. Thus, emerging evidence may provide insights for strategies to target microbiota, immune cells and tumor molecular alterations for colorectal cancer prevention and treatment. Further investigation is needed to clarify the association of Fusobacterium with T-cells and microRNA expressions in colorectal cancer. PMID- 26811608 TI - Preoperative selection of patients with colorectal cancer liver metastasis for hepatic resection. AB - Surgical resection of colorectal liver metastases (CRLM) has a well-documented improvement in survival. To benefit from this intervention, proper selection of patients who would be adequate surgical candidates becomes vital. A combination of imaging techniques may be utilized in the detection of the lesions. The criteria for resection are continuously evolving; currently, the requirements that need be met to undergo resection of CRLM are: the anticipation of attaining a negative margin (R0 resection), whilst maintaining an adequate functioning future liver remnant. The timing of hepatectomy in regards to resection of the primary remains controversial; before, after, or simultaneously. This depends mainly on the tumor burden and symptoms from the primary tumor. The role of chemotherapy differs according to the resectability of the liver lesion(s); no evidence of improved survival was shown in patients with resectable disease who received preoperative chemotherapy. Presence of extrahepatic disease in itself is no longer considered a reason to preclude patients from resection of their CRLM, providing limited extra-hepatic disease, although this currently is an area of active investigations. In conclusion, we review the indications, the adequate selection of patients and perioperative factors to be considered for resection of colorectal liver metastasis. PMID- 26811609 TI - Insight to drug delivery aspects for colorectal cancer. AB - Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide in human beings. Surgery, chemotherapy, radiotherapy and targeted therapies are the conventional four approaches which are currently used for the treatment of CRC. The site specific delivery of chemotherapeutics to their site of action would increase effectiveness with reducing side effects. Targeted oral drug delivery systems based on polysaccharides are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site specific drug delivery to colon increases its concentration at the target site, and thus requires a lower dose and hence abridged side effects. Some novel therapies are also briefly discussed in article such as receptor (epidermal growth factor receptor, folate receptor, wheat germ agglutinin, VEGF receptor, hyaluronic acid receptor) based targeting therapy; colon targeted proapoptotic anticancer drug delivery system, gene therapy. Even though good treatment options are available for CRC, the ultimate therapeutic approach is to avert the incidence of CRC. It was also found that CRCs could be prevented by diet and nutrition such as calcium, vitamin D, curcumin, quercetin and fish oil supplements. Immunotherapy and vaccination are used nowadays which are showing better results against CRC. PMID- 26811610 TI - Approach to the endoscopic resection of duodenal lesions. AB - Duodenal polyps or lesions are uncommonly found on upper endoscopy. Duodenal lesions can be categorized as subepithelial or mucosally-based, and the type of lesion often dictates the work-up and possible therapeutic options. Subepithelial lesions that can arise in the duodenum include lipomas, gastrointestinal stromal tumors, and carcinoids. Endoscopic ultrasonography with fine needle aspiration is useful in the characterization and diagnosis of subepithelial lesions. Duodenal gastrointestinal stromal tumors and large or multifocal carcinoids are best managed by surgical resection. Brunner's gland tumors, solitary Peutz-Jeghers polyps, and non-ampullary and ampullary adenomas are mucosally-based duodenal lesions, which can require removal and are typically amenable to endoscopic resection. Several anatomic characteristics of the duodenum make endoscopic resection of duodenal lesions challenging. However, advanced endoscopic techniques exist that enable the resection of large mucosally-based duodenal lesions. Endoscopic papillectomy is not without risk, but this procedure can effectively resect ampullary adenomas and allows patients to avoid surgery, which typically involves pancreaticoduodenectomy. Endoscopic mucosal resection and its variations (such as cap-assisted, cap-band-assisted, and underwater techniques) enable the safe and effective resection of most duodenal adenomas. Endoscopic submucosal dissection is possible but very difficult to safely perform in the duodenum. PMID- 26811611 TI - Buried bumper syndrome: A complication of percutaneous endoscopic gastrostomy. AB - Percutaneous endoscopic gastrostomy (PEG) is a widely used method of nutrition delivery for patients with long-term insufficiency of oral intake. The PEG complication rate varies from 0.4% to 22.5% of cases, with minor complications being three times more frequent. Buried bumper syndrome (BBS) is a severe complication of this method, in which the internal fixation device migrates alongside the tract of the stoma outside the stomach. Excessive compression of tissue between the external and internal fixation device of the gastrostomy tube is considered the main etiological factor leading to BBS. Incidence of BBS is estimated at around 1% (0.3%-2.4%). Inability to insert, loss of patency and leakage around the PEG tube are considered to be a typical symptomatic triad. Gastroscopy is indicated in all cases in which BBS is suspected. The depth of disc migration in relation to the lamina muscularis propria of the stomach is critical for further therapy and can be estimated by endoscopic or transabdominal ultrasound. BBS can be complicated by gastrointestinal bleeding, perforation, peritonitis, intra-abdominal and abdominal wall abscesses, or phlegmon, and these complications can lead to fatal outcomes. The most important preventive measure is adequate positioning of the external bolster. A conservative approach should be applied only in patients with high operative risk and dismal prognosis. Choice of the method of release is based on the type of the PEG set and depth of disc migration. A disc retained inside the stomach and completely covered by the overgrowing tissue can be released using some type of endoscopic dissection technique (needle knife, argon plasma coagulation, or papillotome through the cannula). Proper patient selection and dissection of the overgrowing tissue are the major determinants for successful endoscopic therapy. A disc localized out of the stomach (lamina muscularis propria) should be treated by a surgeon. PMID- 26811612 TI - Endoscopic ultrasonography guided-fine needle aspiration for the diagnosis of solid pancreaticobiliary lesions: Clinical aspects to improve the diagnosis. AB - Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been applied to pancreaticobiliary lesions since the 1990s and is in widespread use throughout the world today. We used this method to confirm the pathological evidence of the pancreaticobiliary lesions and to perform suitable therapies. Complications of EUS-FNA are quite rare, but some of them are severe. Operators should master conventional EUS observation and experience a minimum of 20-30 cases of supervised EUS-FNA on non-pancreatic and pancreatic lesions before attempting solo EUS-FNA. Studies conducted on pancreaticobiliary EUS-FNA have focused on selection of suitable instruments (e.g., needle selection) and sampling techniques (e.g., fanning method, suction level, with or without a stylet, optimum number of passes). Today, the diagnostic ability of EUS-FNA is still improving; the detection of pancreatic cancer (PC) currently has a sensitivity of 90%-95% and specificity of 95%-100%. In addition to PC, a variety of rare pancreatic tumors can be discriminated by conducting immunohistochemistry on the FNA materials. A flexible, large caliber needle has been used to obtain a large piece of tissue, which can provide sufficient histological information to be helpful in classifying benign pancreatic lesions. EUS-FNA can supply high diagnostic yields even for biliary lesions or peri-pancreaticobiliary lymph nodes. This review focuses on the clinical aspects of EUS-FNA in the pancreaticobiliary field, with the aim of providing information that can enable more accurate and efficient diagnosis. PMID- 26811613 TI - Helicobacter pylori colonization of the oral cavity: A milestone discovery. AB - Over the past several years, the severity of Helicobacter pylori (H. pylori) infections has not significantly diminished. After successful eradication, the annual H. pylori recurrence rate is approximately 13% due to oral H. pylori infection. Established clinical diagnostic techniques do not identify an oral etiologic basis of H. pylori prior to gastric infection. There has been disagreement as to whether oral infection of H. pylori exists or not, with no definite conclusion. In medical practice, negative results with the urea breath test suggest that the stomach infection of H. pylori is cured in these patients. In fact, patients can present negative urea breath test results and yet exhibit H. pylori infection due to oral infection. The present paper provides evidence that H. pylori oral infection is nonetheless present, and the oral cavity represents a secondary site for H. pylori colonization. PMID- 26811614 TI - Helicobacter pylori and colorectal neoplasia: Is there a causal link? AB - Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation. PMID- 26811615 TI - Review of 500 single incision laparoscopic colorectal surgery cases - Lessons learned. AB - Single incision laparoscopic surgery (SILS) is a minimally invasive platform with specific benefits over traditional multiport laparoscopic surgery. The safety and feasibility of SILS has been proven, and the applications continue to grow with experience. After 500 cases at a high-volume, single-institution, we were able to standardize instrumentation and operative steps, as well as develop adaptations in technique to help overcome technical and ergonomic challenges. These technical adaptations have allowed the successful application of SILS to technically difficult patient populations, such as pelvic cases, inflammatory bowel disease cases, and high body mass index patients. This review is a frame of reference for the application and wider integration of the single incision laparoscopic platform in colorectal surgery. PMID- 26811616 TI - Advances in laparoscopy for acute care surgery and trauma. AB - The greatest advantages of laparoscopy when compared to open surgery include the faster recovery times, shorter hospital stays, decreased postoperative pain, earlier return to work and resumption of normal daily activity as well as cosmetic benefits. Laparoscopy today is considered the gold standard of care in the treatment of cholecystitis and appendicitis worldwide. Laparoscopy has even been adopted in colorectal surgery with good results. The technological improvements in this surgical field along with the development of modern techniques and the acquisition of specific laparoscopic skills have allowed for its utilization in operations with fully intracorporeal anastomoses. Further progress in laparoscopy has included single-incision laparoscopic surgery and natural orifice trans-luminal endoscopic surgery. Nevertheless, laparoscopy for emergency surgery is still considered challenging and is usually not recommended due to the lack of adequate experience in this area. The technical difficulties of operating in the presence of diffuse peritonitis or large purulent collections and diffuse adhesions are also given as reasons. However, the potential advantages of laparoscopy, both in terms of diagnosis and therapy, are clear. Major advantages may be observed in cases with diffuse peritonitis secondary to perforated peptic ulcers, for example, where laparoscopy allows the confirmation of the diagnosis, the identification of the position of the ulcer and a laparoscopic repair with effective peritoneal washout. Laparoscopy has also revolutionized the approach to complicated diverticulitis even when intestinal perforation is present. Many other emergency conditions can be effectively managed laparoscopically, including trauma in select hemodynamically-stable patients. We have therefore reviewed the most recent scientific literature on advances in laparoscopy for acute care surgery and trauma in order to demonstrate the current indications and outcomes associated with a laparoscopic approach to the treatment of the most common emergency surgical conditions. PMID- 26811618 TI - Laparoscopic colorectal surgery: Current status and implementation of the latest technological innovations. AB - The introduction of laparoscopy is an example of surgical innovation with a rapid implementation in many areas of surgery. A large number of controlled studies and meta-analyses have shown that laparoscopic colorectal surgery is associated with the same benefits than other minimally invasive procedures, including lesser pain, earlier recovery of bowel transit and shorter hospital stay. On the other hand, despite initial concerns about oncological safety, well-designed prospective randomized multicentre trials have demonstrated that oncological outcomes of laparoscopy and open surgery are similar. Although the use of laparoscopy in colorectal surgery has increased in recent years, the percentages of patients treated with surgery using minimally invasive techniques are still reduced and there are also substantial differences among centres. It has been argued that the limiting factor for the use of laparoscopic procedures is the number of surgeons with adequate skills to perform a laparoscopic colectomy rather than the tumour of patients' characteristics. In this regard, future efforts to increase the use of laparoscopic techniques in colorectal surgery will necessarily require more efforts in teaching surgeons. We here present a review of recent controversies of the use of laparoscopy in colorectal surgery, such as in rectal cancer operations, the possibility of reproducing complete mesocolon excision, and the benefits of intra-corporeal anastomosis after right hemicolectomy. We also describe the results of latest innovations such as single incision laparoscopic surgery, robotic surgery and natural orifice transluminal endoscopic surgery for colon and rectal diseases. PMID- 26811619 TI - Technical feasibility of laparoscopic extended surgery beyond total mesorectal excision for primary or recurrent rectal cancer. AB - Relatively little is known about the oncologic safety of laparoscopic surgery for advanced rectal cancer. Recently, large randomized clinical trials showed that laparoscopic surgery was not inferior to open surgery, as evidenced by survival and local control rates. However, patients with T4 tumors were excluded from these trials. Technological advances in the instrumentation and techniques used by laparoscopic surgery have increased the use of laparoscopic surgery for advanced rectal cancer. High-definition, illuminated, and magnified images obtained by laparoscopy may enable more precise laparoscopic surgery than open techniques, even during extended surgery for T4 or locally recurrent rectal cancer. To date, the quality of evidence regarding the usefulness of laparoscopy for extended surgery beyond total mesorectal excision has been low because most studies have been uncontrolled series, with small sample sizes, and long-term data are lacking. Nevertheless, laparoscopic extended surgery for rectal cancer, when performed by specialized laparoscopic colorectal surgeons, has been reported safe in selected patients, with significant advantages, including a clear visual field and less blood loss. This review summarizes current knowledge on laparoscopic extended surgery beyond total mesorectal excision for primary or locally recurrent rectal cancer. PMID- 26811617 TI - New obesity classification criteria as a tool for bariatric surgery indication. AB - Obesity plays relevant pathophysiological role in the development of health problems, arising as result of complex interaction of genetic, nutritional, and metabolic factors. Due to the role of adipose tissue in lipid and glucose metabolism, and low grade inflammation, it is necessary to classify obesity on the basis of body fat composition and distribution, rather than the simply increase of body weight, and the Body Mass Index. The new term of adiposopathy (''sick fat'') clearly defines the pathogenic role of adipose tissue. Four phenotypes of obese individuals have been described: (1) normal weight obese (NWO); (2) metabolically obese normal weight; (3) metabolically healthy obese; and (4) metabolically unhealthy obese or "at risk" obese. Moreover, sarcopenic obesity has been related to all the phenotypes. The category of normal weight lean, represented by metabolically healthy normal weight has been classified to distinguish from NWO. It is crucial to recommend a bariatric surgery taking into account adiposopathy and sick fat that occurs with the expansion of fat mass, changing the inflammatory and metabolic profile of the patient. Body fat percentage and genetic polymorphism have to be evaluated to personalize the best bariatric surgery intervention. PMID- 26811620 TI - Laparoscopic gastric cancer surgery: Current evidence and future perspectives. AB - Laparoscopic gastrectomy has been widely accepted as a standard alternative for the treatment of early-stage gastric adenocarcinoma because of its favorable short-term outcomes. Although controversies exist, such as establishing clear indications, proper preoperative staging, and oncologic safety, experienced surgeons and institutions have applied this approach, along with various types of function-preserving surgery, for the treatment of advanced gastric cancer. With technical advancement and the advent of state-of-the-art instruments, indications for laparoscopic gastrectomy are expected to expand as far as locally advanced gastric cancer. Laparoscopic gastrectomy appears to be promising; however, scientific evidence necessary to generalize this approach to a standard treatment for all relevant patients and care providers remains to be gathered. Several multicenter, prospective randomized trials in high-incidence countries are ongoing, and results from these trials will highlight the short- and long-term outcomes of the approach. In this review, we describe up-to-date findings and critical issues regarding laparoscopic gastrectomy for gastric cancer. PMID- 26811621 TI - Single-incision laparoscopic surgery for biliary tract disease. AB - Single-incision laparoscopic surgery (SILS), or laparoendoscopic single-site surgery, has been employed in various fields to minimize traumatic effects over the last two decades. Single-incision laparoscopic cholecystectomy (SILC) has been the most frequently studied SILS to date. Hundreds of studies on SILC have failed to present conclusive results. Most randomized controlled trials (RCTs) have been small in scale and have been conducted under ideal operative conditions. The role of SILC in complicated scenarios remains uncertain. As common bile duct exploration (CBDE) methods have been used for more than one hundred years, laparoscopic CBDE (LCBDE) has emerged as an effective, demanding, and infrequent technique employed during the laparoscopic era. Likewise, laparoscopic biliary-enteric anastomosis is difficult to carry out, with only a few studies have been published on the approach. The application of SILS to CBDE and biliary-enteric anastomosis is extremely rare, and such innovative procedures are only carried out by a number of specialized groups across the globe. Herein we present a thorough and detailed analysis of SILC in terms of operative techniques, training and learning curves, safety and efficacy levels, recovery trends, and costs by reviewing RCTs conducted over the past three years and two recently updated meta-analyses. All existing literature on single-incision LCBDE and single-incision laparoscopic hepaticojejunostomy has been reviewed to describe these two demanding techniques. PMID- 26811623 TI - Management of pancreatic cancer in the elderly. AB - Currently, pancreatic adenocarcinoma mainly occurs after 60 years of age, and its prognosis remains poor despite modest improvements in recent decades. The aging of the population will result in a rise in the incidence of pancreatic adenocarcinoma within the next years. Thus, the management of pancreatic cancer in the elderly population is gaining increasing relevance. Older cancer patients represent a heterogeneous group with different biological, functional and psychosocial characteristics that can modify the usual management of this disease, including pharmacokinetic and pharmacodynamic changes, polypharmacy, performance status, comorbidities and organ dysfunction. However, the biological age, not the chronological age, of the patient should be the limiting factor in determining the most appropriate treatment for these patients. Unfortunately, despite the increased incidence of this pathology in older patients, there is an underrepresentation of these patients in clinical trials, and the management of older patients is thus determined by extrapolation from the results of studies performed in younger patients. In this review, the special characteristics of the elderly, the multidisciplinary management of localized and advanced ductal adenocarcinoma of the pancreas and the most recent advances in the management of this condition will be discussed, focusing on surgery, chemotherapy, radiation and palliative care. PMID- 26811622 TI - Viro-immune therapy: A new strategy for treatment of pancreatic cancer. AB - Pancreatic ductal adenocarcinoma (PDAC) is an almost uniformly lethal disease with less than 5% survival at five years. This is largely due to metastatic disease, which is already present in the majority of patients when diagnosed. Even when the primary cancer can be removed by radical surgery, local recurrence occurs within one year in 50%-80% of cases. Therefore, it is imperative to develop new approaches for the treatment of advanced cancer and the prevention of recurrence after surgery. Tumour-targeted oncolytic viruses (TOVs) have become an attractive therapeutic agent as TOVs can kill cancer cells through multiple mechanisms of action, especially via virus-induced engagement of the immune response specifically against tumour cells. To attack tumour cells effectively, tumour-specific T cells need to overcome negative regulatory signals that suppress their activation or that induce tolerance programmes such as anergy or exhaustion in the tumour microenvironment. In this regard, the recent breakthrough in immunotherapy achieved with immune checkpoint blockade agents, such as anti-cytotoxic T-lymphocyte-associate protein 4, programmed death 1 (PD 1) or PD-L1 antibodies, has demonstrated the possibility of relieving immune suppression in PDAC. Therefore, the combination of oncolytic virotherapy and immune checkpoint blockade agents may synergistically function to enhance the antitumour response, lending the opportunity to be the future for treatment of pancreatic cancer. PMID- 26811625 TI - Advances in cryoablation for pancreatic cancer. AB - Pancreatic carcinoma is a common cancer of the digestive system with a poor prognosis. It is characterized by insidious onset, rapid progression, a high degree of malignancy and early metastasis. At present, radical surgery is considered the only curative option for treatment, however, the majority of patients with pancreatic cancer are diagnosed too late to undergo surgery. The sensitivity of pancreatic cancer to chemotherapy or radiotherapy is also poor. As a result, there is no standard treatment for patients with advanced pancreatic cancer. Cryoablation is generally considered to be an effective palliative treatment for pancreatic cancer. It has the advantages of minimal invasion and improved targeting, and is potentially safe with less pain to the patients. It is especially suitable in patients with unresectable pancreatic cancer. However, our initial findings suggest that cryotherapy combined with 125-iodine seed implantation, immunotherapy or various other treatments for advanced pancreatic cancer can improve survival in patients with unresectable or metastatic pancreatic cancer. Although these findings require further in-depth study, the initial results are encouraging. This paper reviews the safety and efficacy of cryoablation, including combined approaches, in the treatment of pancreatic cancer. PMID- 26811624 TI - Molecular targets for the treatment of pancreatic cancer: Clinical and experimental studies. AB - Pancreatic cancer is the fourth most common cause of cancer deaths worldwide. Although recent therapeutic developments for patients with pancreatic cancer have provided survival benefits, the outcomes for patients with pancreatic cancer remain unsatisfactory. Molecularly targeted cancer therapy has advanced in the past decade with the use of a number of pathways as candidates of therapeutic targets. This review summarizes the molecular features of this refractory disease while focusing on the recent clinical and experimental findings on pancreatic cancer. It also discusses the data supporting current standard clinical outcomes, and offers conclusions that may improve the management of pancreatic cancer in the future. PMID- 26811626 TI - Noncoding RNAs and pancreatic cancer. AB - Noncoding RNAs (ncRNAs) represent a class of RNA molecules that typically do not code for proteins. Emerging data suggest that ncRNAs play an important role in several physiological and pathological conditions such as cancer. The best characterized ncRNAs are the microRNAs (miRNAs), which are short, approximately 22-nucleotide sequences of RNA of approximately 22-nucleotide in length that regulate gene expression at the posttranscriptional level, through transcript degradation or translational repression. MiRNAs can function as master gene regulators, impacting a variety of cellular pathways important to normal cellular functions as well as cancer development and progression. In addition to miRNAs, long ncRNAs, which are transcripts longer than 200 nucleotides, have recently emerged as novel drivers of tumorigenesis. However, the molecular mechanisms of their regulation and function, and the significance of other ncRNAs such as piwi interacting RNAs in pancreas carcinogenesis are largely unknown. This review summarizes the growing body of evidence supporting the vital roles of ncRNAs in pancreatic cancer, focusing on their dysregulation through both genetic and epigenetic mechanisms, and highlighting the promise of ncRNAs in diagnostic and therapeutic applications of pancreatic cancer. PMID- 26811627 TI - Mouse models for the discovery of colorectal cancer driver genes. AB - Colorectal cancer (CRC) constitutes a major public health problem as the third most commonly diagnosed and third most lethal malignancy worldwide. The prevalence and the physical accessibility to colorectal tumors have made CRC an ideal model for the study of tumor genetics. Early research efforts using patient derived CRC samples led to the discovery of several highly penetrant mutations (e.g., APC, KRAS, MMR genes) in both hereditary and sporadic CRC tumors. This knowledge has enabled researchers to develop genetically engineered and chemically induced tumor models of CRC, both of which have had a substantial impact on our understanding of the molecular basis of CRC. Despite these advances, the morbidity and mortality of CRC remains a cause for concern and highlight the need to uncover novel genetic drivers of CRC. This review focuses on mouse models of CRC with particular emphasis on a newly developed cancer gene discovery tool, the Sleeping Beauty transposon-based mutagenesis model of CRC. PMID- 26811628 TI - Targeting Wnt/beta-catenin pathway in hepatocellular carcinoma treatment. AB - Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Liver cancer is generally related to hepatitis B or C infection and cirrhosis. Usually, patients with HCC are asymptomatic and are diagnosed at late stages when surgical treatment is no longer suitable. Limited treatment options for patients with advanced HCC are a major concern. Therefore, there is an urge for finding novel therapies to treat HCC. Liver cancer is highly heterogeneous and involved deregulation of several signaling pathways. Wnt/beta catenin pathway is frequently upregulated in HCC and it is implicated in maintenance of tumor initiating cells, drug resistance, tumor progression, and metastasis. A great effort in developing selective drugs to target components of the beta-catenin pathway with anticancer activity is underway but only a few of them have reached phase I clinical trials. We aim to review the role of beta catenin pathway on hepatocarcinogenesis and liver cancer stem cell maintenance. We also evaluated the use of small molecules targeting the Wnt/beta-catenin pathway with potential application for treatment of HCC. PMID- 26811629 TI - Chemokine/chemokine receptor pair CCL20/CCR6 in human colorectal malignancy: An overview. AB - Chemokines belong to a superfamily of small, cytokine-like proteins, which induce multiple physiological functions, particularly cytoskeletal rearrangement and compartment-specific migration through their interaction with G-protein-coupled receptors. Chemokines and their receptors have been widely acknowledged as essential and selective mediators in leukocyte migration in inflammatory response. It is now established that the chemokine/chemokine receptor system is also used by cancer cells to direct lymphatic and haematogenous spreading and additionally has an impact on the site of metastatic growth of different tumours. In recent years an increasing number of studies have drawn attention to CC chemokine cysteine motif chemokine ligand 20 (CCL20) and its physiological sole receptor CCR6 to play a role in the onset, development and metastatic spread of various gastrointestinal cancer entities. Among various cancer types CCR6 was also demonstrated to be significantly overexpressed in colorectal cancer (CRC) and stimulation by its physiological ligand CCL20 has been reported to promote CRC cell proliferation and migration in vitro. Further, the CCL20/CCR6 system apparently plays a role in the organ-selective liver metastasis of CRC. Here we review the literature on expression patterns of CCL20 and CCR6 and their physiological interactions as well as the currently presumed role of CCL20 and CCR6 in the formation of CRC and the development of liver metastasis, providing a potential basis for novel treatment strategies. PMID- 26811630 TI - Stents for colorectal obstruction: Past, present, and future. AB - Since the development of uncovered self-expanding metal stents (SEMS) in the 1990s, endoscopic stents have evolved dramatically. Application of new materials and new designs has expanded the indications for enteral SEMS. At present, enteral stents are considered the first-line modality for palliative care, and numerous types of enteral stents are under development for extended clinical usage, beyond a merely palliative purpose. Herein, we will discuss the current status and the future development of lower enteral stents. PMID- 26811631 TI - Nonampullary duodenal adenoma: Current understanding of its diagnosis, pathogenesis, and clinical management. AB - Nonampullary duodenal adenomas are relatively common in familial adenomatous polyposis (FAP), but nonampullary sporadic duodenal adenomas (SDAs) are rare. Emerging evidence shows that duodenal adenomas, regardless of their anatomic location and whether they are sporadic or FAP-related, share morphologic and molecular features with colorectal adenomas. The available data suggest that duodenal adenomas develop to duodenal adenocarcinomas via similar mechanisms. The optimal approach for management of duodenal adenomas remains to be determined. The techniques for endoscopic resection of duodenal adenoma include snare polypectomy, endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and argon plasma coagulation ablation. EMR may facilitate removal of large duodenal polyps. Although several studies have reported cases of successful ESD for duodenal adenomas, the procedure is technically difficult to perform safely because of the anatomical properties of the duodenum. Although current clinical practice recommends endoscopic resection of all large duodenal adenomas in patients with FAP, endoscopic treatment is usually insufficient to guarantee a polyp-free duodenum. Surgery is indicated for FAP patients with severe polyposis or nonampullary SDAs or FAP-related polyps not amenable to endoscopic resection. Further studies are needed to develop newer endoscopic techniques to guide diagnostic and therapeutic decisions for future management of nonampullary duodenal adenomas. PMID- 26811633 TI - Hepatocyte transplantation program: Lessons learned and future strategies. AB - This review aims to share the lessons we learned over time during the setting of the hepatocyte transplantation (HT) program at the Hepatic Cell Therapy Unit at Hospital La Fe in Valencia. New sources of liver tissue for hepatocyte isolation have been explored. The hepatocyte isolation and cryopreservation procedures have been optimized and quality criteria for assessment of functionality of hepatocyte preparations and suitability for HT have been established. The results indicate that: (1) Only highly viable and functional hepatocytes allow to recover those functions lacking in the native liver; (2) Organs with steatosis (>= 40%) and from elderly donors are declined since low hepatocyte yields, viability and cell survival after cryopreservation, are obtained; (3) Neonatal hepatocytes are cryopreserved without significant loss of viability or function representing high quality cells to improve human HT; (4) Cryopreservation has the advantage of providing hepatocytes constantly available and of allowing the quality evaluation and suitability for transplantation; and (5) Our results from 5 adults with acute liver failure and 4 from children with inborn metabolic diseases, indicate that HT could be a very useful and safe cell therapy, as long as viable and metabolically functional human hepatocytes are used. PMID- 26811632 TI - Status of hepatitis C virus vaccination: Recent update. AB - Hepatitis C virus (HCV) infection is still a major public health problem worldwide since its first identification in 1989. At the start, HCV infection was post-transfusion viral infection, particularly in developing countries. Recently, due to iv drug abuse, HCV infection became number one health problem in well developed countries as well. Following acute HCV infection, the innate immune response is triggered in the form of activated coordinated interaction of NK cells, dendritic cells and interferon alpha. The acquired immune response is then developed in the form of the antibody-mediated immune response (ABIR) and the cell-mediated immune response (CMIR). Both are responsible for clearance of HCV infection in about 15% of infected patients. However, HCV has several mechanisms to evade these antivirus immune reactions. The current review gives an overview of HCV structure, immune response and viral evasion mechanisms. It also evaluates the available preventive and therapeutic vaccines that induce innate, ABIR, CMIR. Moreover, this review highlights the progress in recent HCV vaccination studies either in preclinical or clinical phases. The unsatisfactory identification of HCV infection by the current screening system and the limitations of currently available treatments, including the ineligibility of some chronic HCV patients to such antiviral agents, mandate the development of an effective HCV vaccine. PMID- 26811634 TI - Biomarkers of skin toxicity induced by anti-epidermal growth factor receptor antibody treatment in colorectal cancer. AB - Skin toxicity is a common symptom of anti-epidermal growth factor receptor (EGFR) antibody treatment and is also a predictive marker of its efficacy in colorectal cancer patients. However, severe skin disorders induced by such antibodies negatively impact on the quality of life of patients and decreases drug compliance during treatment. If we can predict the high-risk group susceptible to severe skin toxicity before treatment, we can undertake the early management of any arising skin disorders and formulate a more accurate prognosis for anti-EGFR antibody treatment. Previous studies have identified molecular markers of skin toxicity induced by anti-EGFR antibody, such as EGFR polymorphisms, the expression of inflammatory chemokines and serum levels of EGFR ligands. A clinical trial was undertaken involving the escalation of cetuximab doses, guided by the grade of skin toxicity observed, such as no or low-grade, in metastatic colorectal cancer (the EVEREST study). The dose escalation of cetuximab was confirmed by a safety profile and had the tendency to achieve a higher response rate in KRAS wild-type patients. A large, prospective randomized trial is now ongoing (EVEREST 2) and the results of this trial may contribute to personalized medicine in KRAS wild-type colorectal cancer patients. PMID- 26811635 TI - Diet and nutritional factors in inflammatory bowel diseases. AB - Inflammatory bowel disease (IBD) development is affected by complex interactions between environmental factors, changes in intestinal flora, various predisposing genetic properties and changes in the immune system. Dietary factors seem to play an underestimated role in the etiopathogenesis and course of the disease. However, research about food and IBD is conflicting. An excessive consumption of sugar, animal fat and linoleic acid is considered a risk factor for IBD development, whereas a high fiber diet and citrus fruit consumption may play a protective role. Also, appropriate nutrition in particular periods of the disease may facilitate achieving or prolonging remissions and most of all, improve the quality of life for patients. During disease exacerbation, a low fiber diet is recommended for most patients. In the remission time, an excessive consumption of alcohol and sulfur products may have a negative effect on the disease course. Attempts are also made at employing diets composed in detail in order to supplement IBD therapy. A diet with a modified carbohydrate composition, a semi vegetarian diet and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols are under investigation. Due to chronic inflammation as well as side effects of chronically used medications, patients with IBD are also at increased risk of nutritional factor deficiencies, including iron, calcium, vitamin D, vitamin B12, folic acid, zinc, magnesium and vitamin A. It should also be remembered that there is no single common diet suitable for all IBD patients; each of them is unique and dietary recommendations must be individually developed for each patient, depending on the course of the disease, past surgical procedures and type of pharmacotherapy. PMID- 26811636 TI - Bisphosphonates as potential adjuvants for patients with cancers of the digestive system. AB - Best known for their anti-resorptive activity in bone, bisphosphonates (BPs) have generated interest as potential antineoplastic agents given their pleiotropic biological effects which include antiproliferative, antiangiogenic and immune modulating properties. Clinical studies in multiple malignancies suggest that BPs may be active in the prevention or treatment of cancer. Digestive tract malignancies represent a large and heterogeneous disease group, and the activity of BPs in these cancers has not been extensively studied. Recent data showing that some BPs inhibit human epidermal growth factor receptor (HER) signaling highlight a potential therapeutic opportunity in digestive cancers, many of which have alterations in the HER axis. Herein, we review the available evidence providing a rationale for the repurposing of BPs as a therapeutic adjunct in the treatment of digestive malignancies, especially in HER-driven subgroups. PMID- 26811637 TI - Inflammatory bowel disease imaging: Current practice and future directions. AB - The purpose of this paper is to evaluate the role of imaging in inflammatory bowel disease (IBD), including detection of extraluminal complications and extraintestinal manifestations of IBD, assessment of disease activity and treatment response, and discrimination of inflammatory from fibrotic strictures. IBD is a chronic idiopathic disease affecting the gastrointestinal tract that is comprised of two separate, but related intestinal disorders; Crohn's disease and ulcerative colitis. The paper discusses, in detail the pros and cons of the different IBD imaging modalities that need to be considered in order to optimize the imaging and clinical evaluation of patients with IBD. Historically, IBD evaluation of the bowel has included imaging to assess the portions of the small bowel that are inaccessible to optical endoscopic visualization. This traditionally was performed using barium fluoroscopic techniques; however, cross sectional imaging techniques (computed tomography and magnetic resonance imaging) are being increasingly utilized for IBD evaluation because they can simultaneously assess mural and extramural IBD manifestations. Recent advances in imaging technology, that continue to improve the ability of imaging to noninvasively follow disease activity and treatment response, are also discussed. This review article summarizes the current imaging approach in inflammatory bowel disease as well as the role of emerging imaging modalities. PMID- 26811639 TI - Application of computational methods in genetic study of inflammatory bowel disease. AB - Genetic factors play an important role in the etiology of inflammatory bowel disease (IBD). The launch of genome-wide association study (GWAS) represents a landmark in the genetic study of human complex disease. Concurrently, computational methods have undergone rapid development during the past a few years, which led to the identification of numerous disease susceptibility loci. IBD is one of the successful examples of GWAS and related analyses. A total of 163 genetic loci and multiple signaling pathways have been identified to be associated with IBD. Pleiotropic effects were found for many of these loci; and risk prediction models were built based on a broad spectrum of genetic variants. Important gene-gene, gene-environment interactions and key contributions of gut microbiome are being discovered. Here we will review the different types of analyses that have been applied to IBD genetic study, discuss the computational methods for each type of analysis, and summarize the discoveries made in IBD research with the application of these methods. PMID- 26811638 TI - Protective links between vitamin D, inflammatory bowel disease and colon cancer. AB - Vitamin D deficiency has been associated with a wide range of diseases and multiple forms of cancer including breast, colon, and prostate cancers. Relatively recent work has demonstrated vitamin D to be critical in immune function and therefore important in inflammatory diseases such as inflammatory bowel disease (IBD). Because vitamin D deficiency or insufficiency is increasingly prevalent around the world, with an estimated 30%-50% of children and adults at risk for vitamin D deficiency worldwide, it could have a significant impact on IBD. Epidemiologic studies suggest that low serum vitamin D levels are a risk factor for IBD and colon cancer, and vitamin D supplementation is associated with decreased colitis disease activity and/or alleviated symptoms. Patients diagnosed with IBD have a higher incidence of colorectal cancer than the general population, which supports the notion that inflammation plays a key role in cancer development and underscores the importance of understanding how vitamin D influences inflammation and its cancer-promoting effects. In addition to human epidemiological data, studies utilizing mouse models of colitis have shown that vitamin D is beneficial in preventing or ameliorating inflammation and clinical disease. The precise role of vitamin D on colitis is unknown; however, vitamin D regulates immune cell trafficking and differentiation, gut barrier function and antimicrobial peptide synthesis, all of which may be protective from IBD and colon cancer. Here we focus on effects of vitamin D on inflammation and inflammation-associated colon cancer and discuss the potential use of vitamin D for protection and treatment of IBD and colon cancer. PMID- 26811640 TI - Inflammatory bowel disease associated neoplasia: A surgeon's perspective. AB - Inflammatory bowel disease (IBD) is associated with increased risk of colorectal cancer (CRC). The risk is known to increase with longer duration of the disease, family history of CRC, and history of primary sclerosing cholangitis. The diagnosis of the neoplastic changes associated with IBD is difficult owing to the heterogeneous endoscopic appearance and inter-observer variability of the pathological diagnosis. Screening and surveillance guidelines have been established which aim for early detection of neoplasia. Several surgical options are available for the treatment of IBD-associated neoplasia. Patients' morbidities, risk factors for CRC, degree and the extent of neoplasia must be considered in choosing the surgical treatment. A multidisciplinary team including the surgeon, gastroenterologist, pathologist, and the patient who has a clear understanding of the nature of their disease is needed to optimize outcomes. PMID- 26811641 TI - Disrupted regulatory T cell homeostasis in inflammatory bowel diseases. AB - In the gut, where billions of non-self-antigens from the food and the microbiota are present, the immune response must be tightly regulated to ensure both host protection against pathogenic microorganisms and the absence of immune-related pathologies. It has been well documented that regulatory T cells (Tregs) play a pivotal role in this context. Indeed, Tregs are able to prevent excessive inflammation, which can lead to the rupture of intestinal homeostasis observed in inflammatory bowel diseases (IBDs). Both the worldwide incidence and prevalence of such diseases have increased throughout the latter part of the 20(th) century. Therefore, it is crucial to understand how Tregs suppress the colitogenic immune cells to establish new treatments for patients suffering from IBDs. In this review, we will first summarize the results obtained in animal model studies that highlight the importance of Tregs in maintaining intestinal homeostasis and describe the specific suppressive mechanisms involved. Next, our current knowledge about Tregs contribution to human IBDs will be reviewed, as well as the current therapeutic perspective on using Tregs for clinical IBD treatment and the challenges that remain to be resolved to ensure both the safety and effectiveness of these therapies in targeting this critical immune-regulatory cell population. PMID- 26811643 TI - Assessment of stricturing Crohn's disease: Current clinical practice and future avenues. AB - Crohn's disease (CD) is a chronic remittent idiopathic disease. Although the early phase of the disease is commonly characterized by inflammation-driven symptoms, such as diarrhea, the frequency of fibrostenotic complications in patients with CD increases over the long-term course of the disease. This review presents the current diagnostic options for assessing CD-associated strictures. In addition to the endoscopic evaluation of CD strictures, this review summarizes the currently available imaging modalities, including ultrasound and cross sectional imaging techniques. In addition to stricture detection, differentiating between the primarily inflammatory strictures and the predominantly fibrotic ones is essential for selecting the appropriate treatment strategy (anti-inflammatory medical treatment vs endoscopical or surgical approaches). Therefore, recent imaging advances, such as contrast-enhanced ultrasound and ultrasound elastography, contribute to the development of non-invasive non-radiating imaging of CD-associated strictures. Finally, novel magnetic resonance imaging techniques, such as diffusion-weighted, motility and magnetization transfer imaging, as well as (18)F-FDG PET/CT, molecular imaging approaches and biomarkers, are critically reviewed with regard to their potential role in assessing stricturing CD. PMID- 26811642 TI - Diagnostic imaging advances in murine models of colitis. AB - Inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeutic situations. Murine models of experimental colitis are a vital component of research into human IBD concerning questions of its complex pathogenesis or the evaluation of potential new drugs. To monitor the course of colitis, to the present day, classical parameters like histological tissue alterations or analysis of mucosal cytokine/chemokine expression often require euthanasia of animals. Recent advances mean revolutionary non-invasive imaging techniques for in vivo murine colitis diagnostics are increasingly available. These novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. For the first time, in vivo imaging techniques allow for longitudinal examinations and evaluation of intra-individual therapeutic response. This review discusses the latest developments in the different fields of ultrasound, molecularly targeted contrast agent ultrasound, fluorescence endoscopy, confocal laser endomicroscopy as well as tomographic imaging with magnetic resonance imaging, computed tomography and fluorescence-mediated tomography, discussing their individual limitations and potential future diagnostic applications in the management of human patients with IBD. PMID- 26811644 TI - How to predict clinical relapse in inflammatory bowel disease patients. AB - Inflammatory bowel diseases have a natural course characterized by alternating periods of remission and relapse. Disease flares occur in a random way and are currently unpredictable for the most part. Predictors of benign or unfavourable clinical course are required to facilitate treatment decisions and to avoid overtreatment. The present article provides a literature review of the current evidence on the main clinical, genetic, endoscopic, histologic, serologic and fecal markers to predict aggressiveness of inflammatory bowel disease and discuss their prognostic role, both in Crohn's disease and ulcerative colitis. No single marker seems to be reliable alone as a flare predictor, even in light of promising evidence regarding the role of fecal markers, in particular fecal calprotectin, which has reported good results recently. In order to improve our daily clinical practice, validated prognostic scores should be elaborated, integrating clinical and biological markers of prognosis. Finally, we propose an algorithm considering clinical history and biological markers to intercept patients with high risk of clinical relapse. PMID- 26811645 TI - Protein tyrosine phosphatase non-receptor type 2 and inflammatory bowel disease. AB - Genome wide association studies have associated single nucleotide polymorphisms within the gene locus encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) with the onset of inflammatory bowel disease (IBD) and other inflammatory disorders. Expression of PTPN2 is enhanced in actively inflamed intestinal tissue featuring a marked up-regulation in intestinal epithelial cells. PTPN2 deficient mice suffer from severe intestinal and systemic inflammation and display aberrant innate and adaptive immune responses. In particular, PTPN2 is involved in the regulation of inflammatory signalling cascades, and critical for protecting intestinal epithelial barrier function, regulating innate and adaptive immune responses, and finally for maintaining intestinal homeostasis. On one hand, dysfunction of PTPN2 has drastic effects on innate host defence mechanisms, including increased secretion of pro-inflammatory cytokines, limited autophagosome formation in response to invading pathogens, and disruption of the intestinal epithelial barrier. On the other hand, PTPN2 function is crucial for controlling adaptive immune functions, by regulating T cell proliferation and differentiation as well as maintaining T cell tolerance. In this way, dysfunction of PTPN2 contributes to the manifestation of IBD. The aim of this review is to present an overview of recent findings on the role of PTPN2 in intestinal homeostasis and the impact of dysfunctional PTPN2 on intestinal inflammation. PMID- 26811647 TI - Endothelial dysfunction in inflammatory bowel diseases: Pathogenesis, assessment and implications. AB - Endothelial dysfunction is considered one of the etiological factors of inflammatory bowel disease (IBD). An inflammatory process leads to functional and structural changes in the vascular endothelium. An increase of leukocyte adhesiveness and leukocyte diapedesis, as well as an increased vascular smooth muscle tone and procoagulant activity is observed. Structural changes of the vascular endothelium comprise as well capillary and venule remodeling and proliferation of endothelial cells. Hypoxia in the inflammatory area stimulates angiogenesis by up-regulation of vascular endothelial growth factor, fibroblast growth factor and tumor necrosis factor-alpha. Inflammatory mediators also alter the lymphatic vessel function and impair lymph flow, exacerbating tissue edema and accumulation of dead cells and bacteria. The endothelial dysfunction might be diagnosed by the use of two main methods: physical and biochemical. Physical methods are based on the assessment of large arteries vasodilatation in response to an increased flow and receptors stimulation. Flow-mediated vasodilatation (FMD) is the method that is the most widely used; however, it is less sensitive in detecting early changes of the endothelium function. Most of the studies demonstrated a decrease of FMD in IBD patients but no changes in the carotic intima-media thickness. Biochemical methods of detecting the endothelial dysfunction are based on the assessment of the synthesis of compounds produced both by the normal and damaged endothelium. The endothelial dysfunction is considered an initial step in the pathogenesis of atherosclerosis in the general population. In IBD patients, the risk of cardiovascular diseases is controversial. Large, prospective studies are needed to establish the role of particular medications or dietary elements in the endothelial dysfunction as well to determine the real risk of cardiovascular diseases. PMID- 26811648 TI - Role of antibiotics for treatment of inflammatory bowel disease. AB - Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn's disease (CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms. Antibiotics show a clinical benefit when used for the treatment of pouchitis. The downsides of antibiotic treatment, especially with recurrent or prolonged courses such as used in inflammatory bowel disease, are significant side effects that often cause intolerance to treatment, Clostridium dificile infection, and increasing antibiotic resistance. More studies are needed to define the exact role of antibiotics in inflammatory bowel diseases. PMID- 26811646 TI - Advances in nutritional therapy in inflammatory bowel diseases: Review. AB - Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease are chronic, life-long, and relapsing diseases of the gastrointestinal tract. Currently, there are no complete cure possibilities, but combined pharmacological and nutritional therapy may induce remission of the disease. Malnutrition and specific nutritional deficiencies are frequent among IBD patients, so the majority of them need nutritional treatment, which not only improves the state of nutrition of the patients but has strong anti-inflammatory activity as well. Moreover, some nutrients, from early stages of life are suspected as triggering factors in the etiopathogenesis of IBD. Both parenteral and enteral nutrition is used in IBD therapy, but their practical utility in different populations and in different countries is not clearly established, and there are sometimes conflicting theories concerning the role of nutrition in IBD. This review presents the actual data from research studies on the influence of nutrition on the etiopathogenesis of IBD and the latest findings regarding its mechanisms of action. The use of both parenteral and enteral nutrition as therapeutic methods in induction and maintenance therapy in IBD treatment is also extensively discussed. Comparison of the latest research data, scientific theories concerning the role of nutrition in IBD, and different opinions about them are also presented and discussed. Additionally, some potential future perspectives for nutritional therapy are highlighted. PMID- 26811649 TI - Influence of environmental factors on the onset and course of inflammatory bowel disease. AB - Numerous environmental factors have been linked with inflammatory bowel disease. These include smoking, diet, hygiene, drugs, geographical and psychosocial factors. These factors may either increase the risk of or protect against developing this condition and can also affect the course of illness in a positive or negative manner. A number of studies have examined the influence of environmental factors on inflammatory bowel diseases as a whole as well as on ulcerative colitis and Crohn's disease separately. As there are differences in the pathogenesis of ulcerative colitis and Crohn's disease, the effect of environmental factors on their onset and course is not always similar. Some factors have shown a consistent association, while reports on others have been conflicting. In this article we discuss the current evidence on the roles of these factors on inflammatory bowel disease, both as causative/protective agents and as modifiers of disease course. PMID- 26811650 TI - Quality of life: A critical outcome for all surgical treatments of gastric cancer. AB - Surgery represents the main curative therapeutic modality for gastric cancer, and it is occasionally considered for palliation as well as prophylaxis. Most frequently, surgical outcomes are conveyed in terms of oncological outcomes such as recurrence and survival. However, quality of life (QoL) is also important and should be considered when making treatment decisions - including the extent of and approach to surgery. Measurement of QoL usually involves the application of questionnaires. While there are multiple QoL questionnaires validated for use in oncology patients, there are very few that have been validated for use in those with gastric cancer. In this review, we discuss and compare the current status of QoL questionnaires in gastric cancer. More importantly, the impact of surgery for treatment, palliation and prophylaxis of gastric cancer on QoL will be described. These data should inform the surgeon on the optimal approach to treating gastric cancer, taking into account oncological outcomes. Knowledge gaps are also identified, providing a roadmap for future studies. PMID- 26811651 TI - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer. AB - Gastric cancer associated peritoneal carcinomatosis (GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase the survival in GCPC. Since recurrent gastric cancer remains confined to the abdominal cavity in many patients, regional therapies like aggressive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been investigated for GCPC. HIPEC has been used for three indications in GC- as an adjuvant therapy after a curative surgery, HIPEC has been shown to improve survival and reduce peritoneal recurrences in many randomised trials in Asian countries; as a definitive treatment in established PC, HIPEC along with CRS is the only therapeutic modality that has resulted in long-term survival in select groups of patients; as a palliative treatment in advanced PC with intractable ascites, HIPEC has been shown to control ascites and reduce the need for frequent paracentesis. While the results of randomised trials of adjuvant HIPEC from western centres are awaited, the role of HIPEC in the treatment of GCPC is still evolving and needs larger studies before it is accepted as a standard of care. PMID- 26811652 TI - Adjuvant radiochemotherapy for gastric cancer: Should we use prognostic factors to select patients? AB - Radiotherapy has a not well-established role in the pre-operative and in the post operative setting in gastric cancer (GC) patients. Randomized trials report controversial outcomes and impact on survival. In the D2 loco-regional node resection era, after a well-performed radical surgery, local treatment using radiotherapy combined to chemotherapy should be considered for locally advanced GC. Prognostic factors could help the better selection of subgroups that present high risk of loco-regional recurrence. Then, the addition of radiotherapy could improve the disease-free survival and also quality of life. There are no large prospective studies that have assessed specific factors predicting for recurrence or survival, but only retrospective series, some of them including high number of patients with homogeneous characteristics. In locally advanced GC adding radiotherapy to the post-operative chemotherapy seems to improve outcomes and quality of life. Prognostic factors such as T-stage, N-status, nodal ratio, and other histological factors should be considered to submit patients to post operative combined treatment. Larger prospective series are necessary to investigate the role of combined chemoradiation after radical D2-resection, especially in locally advanced GC. Further prospective investigations are needed to suggest prognostic factors that have significant impact on survival and recurrence, improving the management and outcomes, particularly in locally advanced GC patients. PMID- 26811653 TI - Advanced gastric cancer: What we know and what we still have to learn. AB - Gastric cancer is a common neoplastic disease and, more precisely, is the third leading cause of cancer death in the world, with differences amongst geographic areas. The definition of advanced gastric cancer is still debated. Different stadiating systems lead to slightly different stadiation of the disease, thus leading to variations between the single countries in the treatment and outcomes. In the present review all the possibilities of treatment for advanced gastric cancer have been analyzed. Surgery, the cornerstone of treatment for advanced gastric cancer, is analyzed first, followed by an investigation of the different forms and drugs of chemotherapy and radiotherapy. New frontiers in treatment suggest the growing consideration for intraperitoneal administration of chemotherapeutics and combination of traditional drugs with new ones. Moreover, the necessity to prevent the relapse of the disease leads to the consideration of administering intraperitoneal chemotherapy earlier in the therapeutical algorithm. PMID- 26811654 TI - Personalized medicine in gastric cancer: Where are we and where are we going? AB - Despite improvements in adjuvant therapies for gastric cancer in recent years, the disease is characterized by high recurrence rates and a dismal prognosis. The major improvement in the treatment of recurrent or metastatic gastric cancer in recent years has been the incorporation of trastuzumab, a monoclonal antibody that inhibits human epidermal growth factor receptor 2 (HER2) heterodimerization, after the demonstrated predictive value of the overexpression and/or amplification of this receptor. Beyond HER2, other genetic abnormalities have been identified, and these mutations may be targetable by tyrosine kinase inhibitors or monoclonal antibodies. The demonstration of four distinct molecular subtypes of gastric cancer by the Cancer Genome Atlas study highlight the enormous heterogeneity of the disease and its complex interplay between genetic and epigenetic alterations and provide a roadmap to implement genome-guided personalized therapy in gastric cancer. In the present review, we aim to discuss, from a clinical point of view, the genomic landscape of gastric cancer described in recent studies, the therapeutic insights derived from these findings, and the clinical trials that have been conducted and those in progress that take into account tailored therapies for gastric cancer. PMID- 26811655 TI - Important considerations when contemplating endoscopic resection of undifferentiated-type early gastric cancer. AB - Endoscopic resection (ER) of undifferentiated-type early gastric cancer (UD-EGC) has a lower curative resection (CR) rate than does ER of differentiated-type EGC (D-EGC). However, a low CR rate does not mean that it is unreasonable to schedule ER of UD-EGC. If ER is in fact curative, the long-term outcomes including survival rate are excellent. Quality of life is good because maximal stomach preservation is possible. However, UD-EGC and D-EGC differ histologically. Thus, when ER is contemplated to treat UD-EGC, a careful approach employing strict criteria is essential because the biology of UD-EGC and D-EGC differ. PMID- 26811656 TI - Changing strategies for target therapy in gastric cancer. AB - In spite of a worldwide decrease in the incidence of gastric cancer, this malignancy still remains one of the leading causes of cancer mortality. Great efforts have been made to improve treatment outcomes in patients with metastatic gastric cancer, and the introduction of trastuzumab has greatly improved the overall survival. The trastuzumab treatment took its first step in opening the era of molecular targeted therapy, however several issues still need to be resolved to increase the efficacy of targeted therapy. Firstly, many patients with metastatic gastric cancer who receive trastuzumab in combination with chemotherapeutic agents develop resistance to the targeted therapy. Secondly, many clinical trials testing novel molecular targeted agents with demonstrated efficacy in other malignancies have failed to show benefit in patients with metastatic gastric cancer, suggesting the importance of the selection of appropriate indications according to molecular characteristics in application of targeted agents. Herein, we review the molecular targeted agents currently approved and in use, and clinical trials in patients with metastatic gastric cancer, and demonstrate the limitations and future direction in treatment of advanced gastric cancer. PMID- 26811657 TI - Genomic and epigenomic heterogeneity in molecular subtypes of gastric cancer. AB - Gastric cancer is a complex disease that is affected by multiple genetic and environmental factors. For the precise diagnosis and effective treatment of gastric cancer, the heterogeneity of the disease must be simplified; one way to achieve this is by dividing the disease into subgroups. Toward this effort, recent advances in high-throughput sequencing technology have revealed four molecular subtypes of gastric cancer, which are classified as Epstein-Barr virus positive, microsatellite instability, genomically stable, and chromosomal instability subtypes. We anticipate that this molecular subtyping will help to extend our knowledge for basic research purposes and will be valuable for clinical use. Here, we review the genomic and epigenomic heterogeneity of the four molecular subtypes of gastric cancer. We also describe a mutational meta analysis and a reanalysis of DNA methylation that were performed using previously reported gastric cancer datasets. PMID- 26811658 TI - New blood markers detection technology: A leap in the diagnosis of gastric cancer. AB - Gastric cancer (GC) is still one of the malignant tumors with high morbidity and mortality in the world, with a 5-year survival rate of less than 30%. GC is often either asymptomatic or causes only nonspecific symptoms in its early stages, whereas when the symptoms manifest, the cancer has usually reached an advanced stage, which is one of the main causes of its relatively poor prognosis. Hence, the main focus of GC research has been on discovering new tools and technology to predict, screen and diagnose GC at an early stage which would prompt early treatment. With the tremendous advances in the OMICS technology, serum proteomics has been in the limelight of cancer research over the last few decades and has steered the development of several methods helping to understand the mechanisms underlying gastric carcinogenesis, resulting in the identification of a large number of molecular targets such as circulating tumor cells (CTCs), cell free DNA (cfDNA) and cell tumor DNA (ctDNA) and their sub-molecular components such as miRNA, that show great promise as GC biomarkers. In this review, we are underlying the recent breakthroughs about new blood markers technology for GC while scrutinizing the potential clinical use of CTCs, cfDNA, ctDNA and the role of the methylation of their sub-molecular components in the pathogenesis, diagnosis and management of GC. PMID- 26811660 TI - Group II p21-activated kinases as therapeutic targets in gastrointestinal cancer. AB - P21-activated kinases (PAKs) are central players in various oncogenic signaling pathways. The six PAK family members are classified into group I (PAK1-3) and group II (PAK4-6). Focus is currently shifting from group I PAKs to group II PAKs. Group II PAKs play important roles in many fundamental cellular processes, some of which have particular significance in the development and progression of cancer. Because of their important functions, group II PAKs have become popular potential drug target candidates. However, few group II PAKs inhibitors have been reported, and most do not exhibit satisfactory kinase selectivity and "drug-like" properties. Isoform- and kinase-selective PAK inhibitors remain to be developed. This review describes the biological activities of group II PAKs, the importance of group II PAKs in the development and progression of gastrointestinal cancer, and small-molecule inhibitors of group II PAKs for the treatment of cancer. PMID- 26811659 TI - Emerging roles of non-coding RNAs in gastric cancer: Pathogenesis and clinical implications. AB - Gastric cancer is a leading cause of cancer-related deaths. However, the mechanisms underlying gastric carcinogenesis remain largely unclear. The association of non-coding RNAs (ncRNAs) with cancer has been widely studied during the past decade. In general, ncRNAs have been classified as small ncRNAs, including microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). Emerging evidence shows that miRNAs and lncRNAs play key roles in the formation and progression of many cancers. In this review, we focus on the regulation of miRNAs and lncRNAs in gastric cancer. miRNAs and lncRNAs appear to be involved in gastric tumor growth, invasion, and metastasis and in establishment of the gastric tumor microenvironment through various mechanisms. Furthermore, we also discuss the possibilities of establishing miRNAs and lncRNAs as potential biomarkers and therapeutic targets for gastric cancer. Taken together, we summarize the emerging roles of ncRNAs in gastric cancer development and their possible clinical significance. PMID- 26811661 TI - Clinical approach to incidental pancreatic cysts. AB - The approach to incidentally noted pancreatic cysts is constantly evolving. While surgical resection is indicated for malignant or higher risk cysts, correctly identifying these highest risk pancreatic cystic lesions remains difficult. Using parameters including cyst size, presence of solid components, and pancreatic duct involvement, the 2012 International Association of Pancreatology (IAP) and the 2015 American Gastroenterological Association (AGA) guidelines have sought to identify the higher risk patients who would benefit from further evaluation using endoscopic ultrasound (EUS). Not only can EUS help further assess the presence of solid component and nodules, but also fine needle aspiration of cyst fluid aids in diagnosis by obtaining cellular, molecular, and genetic data. The impact of new endoscopic innovations with novel methods of direct visualization including confocal endomicroscopy require further validation. This review also highlights the differences between the 2012 IAP and 2015 AGA guidelines, which include the thresholds for sending patients for EUS and surgery and methods, interval, and duration of surveillance for unresected cysts. PMID- 26811662 TI - Advanced gastrointestinal endoscopic imaging for inflammatory bowel diseases. AB - Gastrointestinal luminal endoscopy is of paramount importance for diagnosis, monitoring and dysplasia surveillance in patients with both, Crohn's disease and ulcerative colitis. Moreover, with the recent recognition that mucosal healing is directly linked to the clinical outcome of patients with inflammatory bowel disorders, a growing demand exists for the precise, timely and detailed endoscopic assessment of superficial mucosal layer. Further, the novel field of molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy, now encompassing not only diagnosis, surveillance, and treatment but also the prediction of individual therapeutic responses. Within this review, we describe how novel endoscopic approaches and advanced endoscopic imaging methods such as high definition and high magnification endoscopy, dye based and dye-less chromoendoscopy, confocal laser endomicroscopy, endocytoscopy and molecular imaging now allow for the precise and ultrastructural assessment of mucosal inflammation and describe the potential of these techniques for dysplasia detection. PMID- 26811663 TI - Pharmacokinetic drug interactions in liver disease: An update. AB - Inhibition and induction of drug-metabolizing enzymes are the most frequent and dangerous drug-drug interactions. They are an important cause of serious adverse events that have often resulted in early termination of drug development or withdrawal of drugs from the market. Management of such interactions by dose adjustment in clinical practice is extremely difficult because of the wide interindividual variability in their magnitude. This review examines the genetic, physiological, and environmental factors responsible for this variability, focusing on an important but so far neglected cause of variability, liver functional status. Clinical studies have shown that liver disease causes a reduction in the magnitude of interactions due to enzyme inhibition, which is proportional to the degree of liver function impairment. The effect of liver dysfunction varies quantitatively according to the nature, reversible or irreversible, of the inhibitory interaction. The magnitude of reversible inhibition is more drastically reduced and virtually vanishes in patients with advanced hepatocellular insufficiency. Two mechanisms, in order of importance, are responsible for this reduction: decreased hepatic uptake of the inhibitory drug and reduced enzyme expression. The extent of irreversible inhibitory interactions is only partially reduced, as it is only influenced by the decreased expression of the inhibited enzyme. Thus, for appropriate clinical management of inhibitory drug interactions, both the liver functional status and the mechanism of inhibition must be taken into consideration. Although the inducibility of drug metabolizing enzymes in liver disease has long been studied, very conflicting results have been obtained, mainly because of methodological differences. Taken together, the results of early animal and human studies indicated that enzyme induction is substantially preserved in compensated liver cirrhosis, whereas no definitive conclusion as to whether it is significantly reduced in the decompensated state of cirrhosis was provided. Since ethical constraints virtually preclude the possibility of performing methodologically rigorous investigations in patients with severe liver dysfunction, studies have recently been performed in animals rigorously stratified according to the severity of liver insufficiency. The results of these studies confirmed that enzyme induction is virtually unaffected in compensated cirrhosis and indicated that the susceptibility of enzyme induction to severe liver dysfunction depends on the type of nuclear receptor involved and also varies among enzyme isoforms under the transcriptional control of the same nuclear receptor. These findings make it clear that no general conclusion can be reached from the study of any particular enzyme and partly explain the conflicting results obtained by previous studies. Since no general guidelines can be provided for the management of drug interactions resulting from enzyme induction, both the effects and the plasma concentration of the induced drug should be strictly monitored. The findings discussed in this review have important methodological implications as they indicate that, contrary to current guidelines, the magnitude of metabolic drug drug interactions in patients with liver disease cannot be inferred from studies in healthy subjects. PMID- 26811664 TI - Emerging role of Hippo pathway in gastric and other gastrointestinal cancers. AB - More evidence has underscored the importance of Hippo signaling pathway in gastrointestinal tissue homeostasis, whereas its deregulation induces tumorigenesis. Yes-associated protein 1 (YAP1) and its close paralog TAZ, transcriptional co-activator with a PDZ-binding motif, function as key effectors negatively controlled by the Hippo pathway. YAP1/TAZ exerts oncogenic activities by transcriptional regulation via physical interaction with TEAD transcription factors. In various cancers, Hippo pathway cross-talks with pro- or anti tumorigenic pathways such as GPCR, Wnt/beta-catenin, Notch and TGF-beta signaling and is deregulated by multiple factors including cell density/junction and microRNAs. As YAP1 expression is significantly associated with poor prognosis of gastric and other gastrointestinal cancers, detailed delineation of Hippo regulation in tumorigenesis provides novel insight for therapeutic intervention. In current review, we summarized the recent research progresses on the deregulation of Hippo pathway in the gastrointestinal tract including stomach and discuss the molecular consequences leading to tumorigenesis. PMID- 26811665 TI - Recent advances in photodynamic diagnosis of gastric cancer using 5 aminolevulinic acid. AB - Photodynamic diagnosis based on 5-aminolevulinic acid-induced protoporphyrin IX has been clinically applied in many fields based upon its evidenced efficacy and adequate safety. In order to establish a personalized medicine approach for treating gastric cancer patients, rapid intraoperative detection of malignant lesions has become important. Feasibility of photodynamic diagnosis using 5 aminolevulinic acid for gastric cancer patients has been investigated, especially for the detection of peritoneal dissemination and lymph node metastasis. This method enables intraoperative real-time fluorescence detection of peritoneal dissemination, exhibiting higher sensitivity than white light observation without histopathological examination. The method also enables detection of metastatic foci within excised lymph nodes, exhibiting a diagnostic accuracy comparable to that of a current molecular diagnostics technique. Although several complicating issues still need to be resolved, such as the effect of tissue autofluorescence and the insufficient depth penetration of excitation light, this simple and rapid method has the potential to become a useful diagnostic tool for gastric cancer, as well as urinary bladder cancer and glioma. PMID- 26811666 TI - Endoscopic ultrasonography-guided biliary drainage: Who, when, which, and how? AB - Both endoscopic ultrasonography (EUS)-guided choledochoduodenostomy (EUS-CDS) and EUS-guided hepaticogastrostomy (EUS-HGS) are relatively well established as alternatives to percutaneous transhepatic biliary drainage (PTBD). Both EUS-CDS and EUS-HGS have high technical and clinical success rates (more than 90%) in high-volume centers. Complications for both procedures remain high at 10%-30%. Procedures performed by endoscopists who have done fewer than 20 cases sometimes result in severe or fatal complications. When learning EUS-guided biliary drainage (EUS-BD), we recommend a mentor's supervision during at least the first 20 cases. For inoperable malignant lower biliary obstruction, a skillful endoscopist should perform EUS-BD before EUS-guided rendezvous technique (EUS-RV) and PTBD. We should be select EUS-BD for patients having altered anatomy from malignant tumors before balloon-enteroscope-assisted endoscopic retrograde cholangiopancreatography, EUS-RV, and PTBD. If both EUS-CDS and EUS-HGS are available, we should select EUS-CDS, according to published data. EUS-BD will potentially become a first-line biliary drainage procedure in the near future. PMID- 26811667 TI - Antibody markers in the diagnosis of inflammatory bowel disease. AB - Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic intestinal inflammation of unknown etiology. The diagnosis of IBD is based on endoscopic, radiologic and histopathologic criteria. Recently, the search for a noninvasive marker that could augment or replace part of this diagnostic process has become a focus of IBD research. In this review, antibody markers, including microbial antibodies, autoantibodies and peptide antibodies, will be described, focusing on their common features. At present, no single marker with qualities that are satisfactory for the diagnosis and treatment of IBD has been identified, although panels of some antibodies are being evaluated with keen interest. The discovery of novel IBD-specific and sensitive markers is anticipated. Such markers could minimize the use of endoscopic and radiologic examinations and could enable clinicians to implement individualized treatment plans designed to improve the long-term prognosis of patients with IBD. PMID- 26811668 TI - Helicobacter pylori associated gastric intestinal metaplasia: Treatment and surveillance. AB - Gastric cancer (GC) is one of the leading causes of cancer related death in the world, particularly in East Asia. According to the Correa's cancer cascade, non cardia GC is usually developed through a series of mucosal changes from non atrophic gastritis to atrophic gastritis (AG), intestinal metaplasia (IM), dysplasia and adenocarcinoma. Atrophic gastritis and IM are therefore generally considered to be pre-neoplastic gastric lesions. Helicobacter pylori (H. pylori) infection is an important initiating and promoting step of this gastric carcinogenesis cascade. Emerging long-term data showed that eradication of H. pylori reduced the risk of subsequent cancer development. It however remains confusing whether eradication of the bacterium in individuals with pre-neoplastic gastric lesions could regress these changes as well as in preventing cancer. Whilst H. pylori eradication could likely regress AG, the presence of IM may be a point of no return in this cascade. Hence, surveillance by endoscopy may be indicated in those with extensive IM or those with incomplete IM, particularly in populations with high GC risk. The optimal interval and the best tool of surveillance endoscopy remains to be determined in future studies. PMID- 26811669 TI - Cytomegalovirus in inflammatory bowel disease: A systematic review. AB - AIM: To identify definitions of cytomegalovirus (CMV) infection and intestinal disease, in inflammatory bowel disease (IBD), to determine the prevalence associated with these definitions. METHODS: We conducted a systematic review and interrogated PubMed, EMBASE and Cochrane for literature on prevalence and diagnostics of CMV infection and intestinal disease in IBD patients. As medical headings we used "cytomegalovirus" OR "CMV" OR "cytomegalo virus" AND "inflammatory bowel disease" OR "IBD" OR "ulcerative colitis" OR "colitis ulcerosa" OR "Crohn's disease". Both MeSH-terms and free searches were performed. We included all types of English-language (clinical) trials concerning diagnostics and prevalence of CMV in IBD. RESULTS: The search strategy identified 924 citations, and 52 articles were eligible for inclusion. We identified 21 different definitions for CMV infection, 8 definitions for CMV intestinal disease and 3 definitions for CMV reactivation. Prevalence numbers depend on used definition, studied population and region. The highest prevalence for CMV infection was found when using positive serum PCR as a definition, whereas for CMV intestinal disease this applies to the use of tissue PCR > 10 copies/mg tissue. Most patients with CMV infection and intestinal disease had steroid refractory disease and came from East Asia. CONCLUSION: We detected multiple different definitions used for CMV infection and intestinal disease in IBD patients, which has an effect on prevalence numbers and eventually on outcome in different trials. PMID- 26811670 TI - Spotlight on ixazomib: potential in the treatment of multiple myeloma. AB - Despite the significant therapeutic advances achieved with proteasome inhibitors (PIs) such as bortezomib and carfilzomib in prolonging the survival of patients with multiple myeloma, the development of drug resistance, peripheral neuropathy, and pharmacokinetic limitations continue to pose major challenges when using these compounds. Ixazomib is a second-generation PI with improved activity over other PIs. Unlike bortezomib and carfilzomib, which are administered by injection, ixazomib is the first oral PI approved by US Food and Drug Administration. This review discusses the biochemical properties, mechanisms of action, preclinical efficacy, and clinical trial results leading to the US Food and Drug Administration approval of ixazomib. PMID- 26811672 TI - Factors contributing to nonadherence to follow-up appointments in a resident glaucoma clinic versus primary eye care clinic. AB - PURPOSE: To determine the rate of adherence to follow-up appointment recommendations in a resident glaucoma clinic with no mechanism for reminders, compared to a resident cataract and primary eye care (CPEC) clinic in which telephone reminders were used, and to identify factors that contribute to adherence in each patient group. METHODS: This retrospective cohort study included subjects in the CPEC clinic who received telephone reminders and those in the glaucoma clinic who did not. Each sample was selected to have a similar proportion of follow-up recommendations for 1, 3, and 6 months. Subjects were considered adherent if they returned within a specified timeframe. RESULTS: A total of 144 subjects from the glaucoma clinic and 151 subjects from the CPEC clinic were included. There was no significant difference between follow-up adherence rates of patients who received telephone reminders and those who did not (odds ratio [OR] =1.35, 95% confidence interval [CI] 0.79-2.32, P=0.28). Patients who were on more than two ocular medications were more likely to return for follow-up (OR=3.11, 95% CI 1.53-6.35, P=0.0018). Subjects between the ages 50 and 80 years were more likely to be adherent compared to their younger and older peers (P=0.02). CONCLUSION: The follow-up adherence of patients in a CPEC clinic who received telephone reminders was similar to patients in a glaucoma clinic who did not receive any intervention to increase their adherence. Younger (?50 years old) and elderly (?80 years old) subjects, as well as patients using less than two glaucoma medications, were less likely to adhere to their follow-up appointments. PMID- 26811673 TI - Silver nanoparticle ink technology: state of the art. AB - Printed electronics will bring to the consumer level great breakthroughs and unique products in the near future, shifting the usual paradigm of electronic devices and circuit boards from hard boxes and rigid sheets into flexible thin layers and bringing disposable electronics, smart tags, and so on. The most promising tool to achieve the target depends upon the availability of nanotechnology-based functional inks. A certain delay in the innovation-transfer process to the market is now being observed. Nevertheless, the most widely diffused product, settled technology, and the highest sales volumes are related to the silver nanoparticle-based ink market, representing the best example of commercial nanotechnology today. This is a compact review on synthesis routes, main properties, and practical applications. PMID- 26811671 TI - Pasireotide: a novel treatment for patients with acromegaly. AB - Morbidity and mortality rates in patients with active acromegaly are higher than the general population. Adequate biochemical control restores mortality to normal rates. Now, medical therapy has an increasingly important role in the treatment of patients with acromegaly. Somatostatin receptor ligands (SRLs) are considered the standard medical therapy, either after surgery or as a first-line therapy when surgery is deemed ineffective or is contraindicated. Overall, octreotide and lanreotide are first-generation SRLs and are effective in ~20%-70% of patients. Pegvisomant, a growth hormone receptor antagonist, controls insulin-like growth factor 1 in 65%-90% of cases. Consequently, a subset of patients (nonresponders) requires other treatment options. Drug combination therapy offers the potential for more efficacious disease control. However, the development of new medical therapies remains essential. Here, emphasis is placed on new medical therapies to control acromegaly. There is a focus on pasireotide long-acting release (LAR) (Signifor LAR(r)), which was approved in 2014 by the US Food and Drug Administration and the European Medicine Agency for the treatment of acromegaly. Pasireotide LAR is a long-acting somatostatin multireceptor ligand. In a Phase III clinical trial in patients with acromegaly (naive to medical therapy or uncontrolled on a maximum dose of first-generation SRLs), 40 and 60 mg of intramuscular pasireotide LAR achieved better biochemical disease control than octreotide LAR, and tumor shrinkage was noted in both pasireotide groups. Pasireotide LAR tolerability was similar to other SRLs, except for a greater frequency and degree of hyperglycemia and diabetes mellitus. Baseline glucose may predict hyperglycemia occurrence after treatment, and careful monitoring of glycemic status and appropriate treatment is required. A precise definition of patients with acromegaly who will derive the greatest therapeutic benefit from pasireotide LAR remains to be established. Lastly, novel therapies and new potential delivery modalities (oral octreotide) are summarized. PMID- 26811674 TI - Benefits of use, and tolerance of, medium-chain triglyceride medical food in the management of Japanese patients with Alzheimer's disease: a prospective, open label pilot study. AB - OBJECTIVES: This is the first clinical trial of this type in Japan, designed to analyze two important aspects of Alzheimer's disease (AD) management using medium chain triglycerides. Axona was administered for 3 months (40 g of powder containing 20 g of caprylic triglycerides). We used an indurating, four-step dose titration method (from 10 to 40 g per day) for 7 days before the trial, and examined the tolerance and adverse effects of this intervention. We also investigated its effect on cognitive function in mild-to-moderate AD patients. PATIENTS AND METHODS: This was a clinical intervention in 22 Japanese patients with sporadic AD at a mild-to-moderate stage (ten females, 12 males), mean age (+/- standard deviation) 63.9 (+/-8.5) years, Mini-Mental State Examination (MMSE) score, 10-25, seven patients were ApoE4-positive. During Axona administration, we examined changes in cognitive function by obtaining MMSE and AD assessment-scale scores. Intolerance and serum ketone concentrations were also examined. RESULTS: The tolerance of Axona was good, without severe gastrointestinal adverse effects. Axona did not improve cognitive function in our sample of AD patients, even in those patients without the ApoE4 allele. However, some ApoE4-negative patients with baseline MMSE score >=14 showed improvement in their cognitive functions. CONCLUSION: The modified dose-titration method, starting with a low dose of Axona, decreased gastrointestinal adverse effects in Japanese patients. Axona might be effective for some relatively mildly affected patients with AD (with cognitive function MMSE score of >=14 and lacking the ApoE4 allele). PMID- 26811676 TI - The effect of postgastrectomy reflux on lung functions. PMID- 26811675 TI - Associations of frailty and psychosocial factors with autonomy in daily activities: a cross-sectional study in Italian community-dwelling older adults. AB - Frailty has been recognized as a risk factor for geriatric adverse events. Little is known of the role of psychosocial factors associated with frailty in explaining negative outcomes of aging. This study was aimed at 1) evaluating the differences in psychosocial factors among robust, prefrail, and frail individuals and 2) investigating whether there was any interaction effect of frailty status with empirically identified clusters of psychosocial factors on autonomy in the activities of daily living (ADLs). Two-hundred and ten older adults (age 73+/-6 years, 66% women) were involved in this study. Frailty was assessed using an adapted version of the frailty phenotype. The psychosocial factors investigated were depressive symptoms using the 20-item Center for Epidemiologic Studies Depression Scale, social isolation using the Friendship Scale, and loneliness feeling using the eight-item UCLA Loneliness Scale. The autonomy in ADLs was measured with the Groningen Activity Restriction Scale. Thirty-one percent of participants were robust, 55% prefrail, and 14% frail. We performed an analysis of covariance which showed differences between robust, prefrail, and frail individuals for all the psychosocial variables: Center for Epidemiologic Studies Depression Scale, F(2, 205)=18.48, P<0.001; Friendship Scale, F(2, 205)=4.59, P=0.011; UCLA Loneliness Scale, F(2, 205)=5.87, P=0.003, controlling for age and sex. Using the same covariates, the two-way analysis of covariance indicated an interaction effect of frailty with psychosocial factors in determining ADLs, F(4, 199)=3.53, P=0.008. This study demonstrates the close relationship between frailty and psychosocial factors, suggesting the need to take into account simultaneously physical and psychosocial components of human functioning. PMID- 26811677 TI - A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer. AB - Castrate-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Several tyrosine kinases have been implicated in the development and growth of CRPC, as such targeting these kinases may offer an alternative therapeutic strategy. We established the combination of two tyrosine kinase inhibitors (TKIs), sorafenib and nilotinib, as the most cytotoxic. In addtion, to improve their bioavailability and reduce their metabolism, we encapsulated sorafenib and nilotinib into styrene-co-maleic acid micelles. The micelles' charge, size, and release rate were characterized. We assessed the effect of the combination on the cytotoxicity, cell cycle, apoptosis, protein expression, tumor spheroid integrity, migration, and invasion. The micelles exhibited a mean diameter of 100 nm, a neutral charge, and appeared highly stable. The micellar TKIs promoted greater cytotoxicity, decreased cell proliferation, and increased apoptosis relative to the free TKIs. In addition, the combination reduced the expression and activity of several tyrosine kinases and reduced tumor spheroid integrity and metastatic potential of CRPC cell lines more efficiently than the single treatments. The combination increased the therapeutic potential and demonstrated the relevance of a targeted combination therapy for the treatment of CRPC. In addition, the efficacy of the encapsulated drugs provides the basis for an in vivo preclinical testing. PMID- 26811679 TI - Safety and efficacy of paliperidone extended-release in Chinese patients with schizophrenia: a 24-week, open-label extension of a randomized, double-blind, placebo-controlled study. AB - OBJECTIVES: The long-term safety, tolerability, and efficacy of paliperidone extended-release (ER) were evaluated in Chinese patients with schizophrenia. METHODS: Patients (aged >=18 years) with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria) who had completed run-in (8-week), stabilization (6-week), and double-blind (DB) phases (variable) of a phase-3, placebo-controlled study entered this 24-week, open-label extension (OLE) study. These patients, who had either experienced a relapse or remained relapse-free through DB phase of the study, were treated with flexible-dose paliperidone-ER (3-12 mg/day) during the OLE phase. Major safety evaluations included treatment-emergent adverse events (TEAEs) and extrapyramidal symptoms. Efficacy endpoints included changes in Positive and Negative Syndrome Scale total score, Clinical Global Impression-Severity scale, and Personal and Social Performance scale from OLE baseline to OLE endpoint. RESULTS: Out of 106 patients who entered the OLE phase (placebo: 59, paliperidone-ER: 47), a total of 85 (80%) completed it. Thirty-five (33%) patients experienced at least one TEAE; most common were akathisia, somnolence, nasopharyngitis, and constipation (3.8% each). Serious TEAEs were noted in two patients (completed suicide; schizophrenia worsening). No TEAEs with an onset during the OLE phase led to discontinuation. Extrapyramidal symptoms related-TEAEs were reported in eight (7.5%) patients. Mean (standard deviation) changes in Positive and Negative Syndrome Scale total scores (-10.4 [13.2]), Clinical Global Impression-Severity scores (-0.6 [0.96]) and Personal and Social Performance scores (7.4 [13.2]) from OLE baseline to OLE endpoint showed patients who had been treated with placebo during the DB phase experienced more pronounced improvements. CONCLUSION: In this OLE study, flexibly dosed paliperidone-ER (3-12 mg/day) was tolerable and efficacious in Chinese patients with schizophrenia. PMID- 26811678 TI - A new target ligand Ser-Glu for PEPT1-overexpressing cancer imaging. AB - Nanoparticles functionalized with active target ligands have been widely used for tumor-specific diagnosis and therapy. The target ligands include antibodies, peptides, proteins, small molecules, and nucleic acid aptamers. Here, we utilize dipeptide Ser-Glu (DIP) as a new ligand to functionalize polymer-based fluorescent nanoparticles (NPs) for pancreatic cancer target imaging. We demonstrate that in the first step, Ser-Glu-conjugated NPs (NPs-DIP) efficiently bind to AsPC-1 and in the following NPs-DIP are internalized into AsPC-1 in vitro. The peptide transporter 1 inhibition experiment reveals that the targeting effects mainly depend on the specific binding of DIP to peptide transporter 1, which is remarkably upregulated in pancreatic cancer cells compared with varied normal cells. Furthermore, NPs-DIP specifically accumulate in the site of pancreatic tumor xenograft and are further internalized into the tumor cells in vivo after intravenous administration, indicating that DIP successfully enhanced nanoparticles internalization efficacy into tumor cells in vivo. This work establishes Ser-Glu to be a new tumor-targeting ligand and provides a promising tool for future tumor diagnostic or therapeutic applications. PMID- 26811681 TI - Treatment discontinuation and tolerability as a function of dose and titration of duloxetine in the treatment of major depressive disorder. AB - PURPOSE: We sought to better understand how dose and titration with duloxetine treatment may impact tolerability and treatment discontinuation in patients with major depressive disorder. PATIENTS AND METHODS: We investigated Phase III duloxetine trials. Group 1 was a single placebo-controlled study with a 20 mg initial dose and a slow titration to 40 and 60 mg. Group 2 was a single study with a 40 mg initial dose and final "active" doses of 40 and 60 mg (5 mg control group), with 1-week titration. Group 3 consisted of eight placebo-controlled studies with starting doses of 40, 60, and 80 mg/day with minimal titration (final dose 40-120 mg/day). Tolerability was measured by rate of discontinuation due to adverse events (DCAE). RESULTS: The DCAE in Group 1 were 3.6% in the 60 mg group, 3.3% in the 40 mg group, and 3.2% in the placebo group. In Group 2, the DCAE were 15.0% in the 60 mg group, 8.1% in the 40 mg group, and 4.9% in the 5 mg group. In Group 3, the DCAE were 9.7% and 4.2% in the duloxetine and placebo groups, respectively. CONCLUSION: This study suggests that starting dose and titration may have impacted tolerability and treatment discontinuation. A lower starting dose of duloxetine and slower titration may contribute to improving treatment tolerability for patients with major depressive disorder. PMID- 26811680 TI - Optimal management of ADHD in older adults. AB - BACKGROUND: The manifestation of attention-deficit/hyperactivity disorder (ADHD) among older adults has become an interesting topic of interest due to an increasing number of adults aged 50 years and older (>=50 years) seeking assessment for ADHD. Unfortunately, there is a lack of research on ADHD in older adults, and until recently only a few case reports existed. METHOD: A systematic search was conducted in the databases Medline/PubMed and PsycINFO in order to identify studies regarding ADHD in adults >=50 years. RESULTS: ADHD persists into older ages in many patients, but the prevalence of patients fulfilling the criteria for the diagnosis at age >=50 years is still unknown. It is reason to believe that the prevalence is falling gradually with age, and that the ADHD symptom level is significantly lower in the age group 70-80 years than the group 50-60 years. There is a lack of controlled studies of ADHD medication in adults >=50 years, but this review suggests that many patients aged >=50 years experience beneficial effects of pharmacological treatment. The problem with side effects and somatic complications may rise to a level that makes pharmacotherapy for ADHD difficult after the age of 65 years. Physical assessment prior to initiation of ADHD medication in adults >=50 years should include a thorough clinical examination, and medication should be titrated with low doses initially and with a slow increase. In motivated patients, different psychological therapies alone or in addition to pharmacotherapy should be considered. CONCLUSION: It is essential when treating older adult patients with ADHD to provide good support based on knowledge and understanding of how ADHD symptoms have affected health, quality of life, and function through the life span. Individualized therapy for each elderly patient should be recommended to balance risk-benefit ratio when pharmacotherapy is considered to be a possible treatment. PMID- 26811683 TI - Synesthetic associations and psychosensory symptoms of temporal epilepsy. AB - BACKGROUND: Synesthesia manifests as unusual associative connections that may cause intriguing experiences due to various cross-modal connections, for example, a sound may be experienced as color. Several findings indicate that temporal lobe seizures or seizure-like conditions and increased excitability may influence various unusual cross-sensory links and synesthetic experiences. METHODS: In this context, the purpose of this study is to find relationships between word-color associations and psychopathological symptoms related to temporal lobe epilepsy and limbic irritability (Limbic System Checklist [LSCL-33]), symptoms of traumatic stress (Trauma Symptoms Checklist [TSC-40]), and depressive symptoms (Beck Depression Inventory [BDI-II]) in 71 participants (mean age =25.23 years) recruited from the general population. The whole sample included two subgroups according to levels of psychosensory and affective symptoms related to temporal epilepsy measured by LSCL-33. RESULTS: The results in both subgroups indicate specific words correlated with the scores of psychopathological symptoms measured by LSCL-33, BDI-II, and TSC-40. Significant Spearman correlations have been predominantly found in the subgroup of participants with higher levels of LSCL 33. CONCLUSION: The results indicate a specific synesthetic-like mechanism in association processes that reflects psychopathological symptoms related to increased temporo-limbic excitability. PMID- 26811682 TI - Targets, attitudes, and goals of psychiatrists treating patients with schizophrenia: key outcome drivers, role of quality of life, and place of long acting antipsychotics. AB - PURPOSE: This survey of Italian psychiatrists was conducted to better define drivers of schizophrenia treatment choice in real-life practice, particularly for use of long-acting injectable (LAI) antipsychotics. METHODS: Between October 15 and December 15, 2014, 1,000 surveys were sent to psychiatrists who treat schizophrenic patients; 709 completed questionnaires were analyzed (71% response rate). RESULTS: The two most important factors determining therapy success were efficacy (75% of responses) and tolerability (45%) followed by global functioning (24%) and quality of life (17%). LAI antipsychotics were most often used to facilitate regular treatment monitoring (49%), and 41% of psychiatrists thought that patients with low adherence who had failed oral therapy were well-suited for LAI antipsychotics. Only 4% of respondents saw LAI antipsychotics as appropriate for patients without other therapeutic options. CONCLUSION: Although efficacy and tolerability were the most common factors used to evaluate treatment success in schizophrenia, psychiatrists also consider QoL and global functioning to be important. PMID- 26811684 TI - Critical evaluation of paliperidone in the treatment of schizophrenia in Chinese patients: a systematic literature review. AB - BACKGROUND: Paliperidone (9-hydroxyrisperidone), the major active metabolite of risperidone, has been introduced as a novel atypical antipsychotic agent in many countries. It is available both as an oral extended-release (ER) formulation and as a long-acting injection (paliperidone palmitate, PP), which have been approved for treating schizophrenia in the People's Republic of China since 2009 and 2012, respectively. This systematic review summarizes the efficacy, effectiveness, and safety of paliperidone in the treatment of schizophrenia in the Chinese population. METHODS: A systematic literature search was conducted on the databases covering international and Chinese core journals, published from January 1, 2008, to May 22, 2015. RESULTS: A total of 122 publications were retrieved, of which 63 studies were identified for inclusion; most studies were related to paliperidone ER (n=53), nine were related to PP, and one study was related to both agents. Paliperidone ER demonstrated at least comparable efficacy with active comparators, including risperidone, olanzapine, ziprasidone, or aripiprazole, and was found to be superior with respect to the onset of action and improvement in the Personal and Social Performance Scale score. Paliperidone ER appeared to be associated with a lower risk of metabolic syndromes; the most common treatment-emergent adverse events were extrapyramidal symptoms, akathisia, insomnia, and somnolence. Results from interventional and observational studies showed that PP was also an effective and well-tolerated treatment for Chinese patients with schizophrenia. The findings were generally consistent with those observed in non-Chinese populations. CONCLUSION: Both paliperidone ER and PP were effective and well-tolerated agents for the treatment of schizophrenia in the Chinese population according to the data we reviewed. No new safety signals specific for the Chinese population were raised for paliperidone. Further studies may be needed to collect more data on long-term treatment of schizophrenia in the People's Republic of China. PMID- 26811685 TI - Treatment of Rockwood type III acromioclavicular joint dislocation using autogenous semitendinosus tendon graft and endobutton technique. AB - BACKGROUND: The aim of this study was to evaluate the therapeutic effect of autogenous semitendinosus graft and endobutton technique, and compare with hook plate in treatment of Rockwood type III acromioclavicular (AC) joint dislocation. METHODS: From April 2012 to April 2013, we treated 46 patients with Rockwood type III AC joint dislocation. Patients were randomly divided into two groups: Group A was treated using a hook plate and Group B with autogenous semitendinosus graft and endobutton technique. All participants were followed up for 12 months. Radiographic examinations were performed every 2 months postoperatively, and clinical evaluation was performed using the Constant-Murley score at the last follow-up. RESULTS: Results indicated that patients in Group B showed higher mean scores (90.3+/-5.4) than Group A (80.4+/-11.5) in terms of Constant-Murley score (P=0.001). Group B patients scored higher in terms of pain (P=0.002), activities (P=0.02), range of motion (P<0.001), and strength (P=0.004). In Group A, moderate pain was reported by 2 (8.7%) and mild pain by 8 (34.8%) patients. Mild pain was reported by 1 (4.3%) patient in Group B. All patients in Group B maintained complete reduction, while 2 (8.7%) patients in Group A experienced partial reduction loss. Two patients (8.7%) encountered acromial osteolysis on latest radiographs, with moderate shoulder pain and limited range of motion. CONCLUSION: Autogenous semitendinosus graft and endobutton technique showed better results compared with the hook plate method and exhibited advantages of fewer complications such as permanent pain and acromial osteolysis. PMID- 26811686 TI - Profile of eliglustat tartrate in the management of Gaucher disease. AB - Gaucher disease (GD) is a lysosomal storage disorder caused by the deficient activity of acid beta glucosidase, with consequent accumulation of glucosylceramide in the spleen, liver, bone marrow, and various organs and tissues. Currently, the gold standard for GD treatment is enzyme replacement therapy (ERT). The efficacy of ERT in improving or stabilizing the visceral and hematological symptoms of GD is well-proven. However, since ERT has to be administered by frequent intravenous infusions, this therapeutic approach has an important impact on the patient's quality of life. Eliglustat tartrate is a new substrate reduction therapy for GD, which acts as a specific and potent inhibitor of glucosylceramide synthase and can be administered orally. This review summarizes the results of the preclinical and clinical trials, which experimented with eliglustat, and discusses its possible role in the management of GD, when compared to the currently available treatments and the new experimental approaches. PMID- 26811687 TI - Critical evaluation of the MitraClip system in the management of mitral regurgitation. AB - The MitraClip (MC) system is a device for percutaneous, transseptal edge-to-edge reconstruction of the mitral valve (MV) in patients with severe mitral regurgitation (MR) not eligible for surgery. Recently, a number of studies have underlined the therapeutic benefit of the MC system for patients with extreme and high risk for MV surgery suffering from either degenerative or functional MR. The MC procedure shows negligible intraprocedural mortality, low periprocedural complication rates, and a significant reduction in MR, as well as an improvement in functional capacity and most importantly quality of life. Presently, the MC system has become an additional interventional tool in the concert of surgical methods. It hereby enlarges the spectrum of MV repair for the Heart Team. Lately, many reviews focused on the MC system. The current review describes the developments in the treatment of MR with the MC system. PMID- 26811689 TI - Patients harboring EGFR mutation after primary resistance to crizotinib and response to EGFR-tyrosine kinase inhibitor. AB - Anaplastic lymphoma kinase (ALK) rearrangement lung cancer responds to ALK tyrosine kinase inhibitors. It is known that many cases ultimately acquired resistance to crizotinib. However, a case of primary resistance is rare. We present a case of harboring exon 19 deletion in epidermal growth factor receptor in ALK rearranged lung adenocarcinoma, who experienced a partial tumor response to icotinib after failure with crizotinib therapy and chemotherapy. Considering the partial response, we conclude that it is important to find the cause of resistance to crizotinib. We detected gene mutations with plasma by the next generation sequencing; the next-generation sequencing demonstrates an attractive system to identify mutations improving the outcome of patients with a deadly disease. PMID- 26811688 TI - Bioinformatics analysis of hepatitis C virus genotype 2a-induced human hepatocellular carcinoma in Huh7 cells. AB - Hepatocellular carcinoma (HCC) is a liver cancer that could be induced by hepatitis C virus genotype 2a Japanese fulminant hepatitis-1 (JFH-1) strain. The aim of this study was to investigate the molecular mechanisms of HCC. The microarray data GSE20948 includes 14 JFH-1- and 14 mock (equal volume of medium [control])-infected Huh7 samples. The data were downloaded from the Gene Expression Omnibus. After data processing, soft cluster analyses were performed to identify co-regulated genes with similar temporal expression patterns. Functional and pathway enrichment analyses, as well as functional annotation analysis, were performed. Subsequently, combined networks of protein-protein interaction network, microRNA regulatory network, and transcriptional regulatory network were constructed. Hub nodes, modules, and five clusters of co-regulated genes were also identified. In total, 173 up and 207 down co-regulated genes were separately identified in JFH-1-infected Huh7 cells compared with those of control cells. Functional enrichment analysis indicated that up co-regulated genes were related to skeletal system morphogenesis and neuron differentiation and down co regulated genes were related to steroid/cholesterol/sterol metabolisms. Hub genes (such as IRF1, GBP1, ICAM1, Foxa1, DHCR7, HMGCS2, and MSMO1) were identified. Transcription factors IRF1 and Foxa1 were the targets of miR-130a, miR-17-5p, and miR-20a. PPARGC1A was targeted by miR-29 family, and MSMO1 was the target of miR 23 family. Hub nodes (such as IRF1, GBP1, ICAM1, Foxa1, DHCR7, HMGCS2, and MSMO1) and microRNAs might be used as candidate biomarkers of JFH-1-infected HCC. PMID- 26811690 TI - Decreased expression levels of PIWIL1, PIWIL2, and PIWIL4 are associated with worse survival in renal cell carcinoma patients. AB - Piwi-interacting RNAs (piRNAs) are a newly discovered class of small non-coding RNAs involved in silencing of transposable elements and in sequence-specific chromatin modifications. PIWI proteins (PIWIL), which belong to the family of Argonaute genes/proteins, bind to piRNAs and function mainly in germ line cells, but more recently were described to be functional also in stem cells and cancer cells. To date, there have been four PIWI proteins discovered in humans: PIWIL1, PIWIL2, PIWIL3, and PIWIL4. Recent studies suggested that deregulated expression of PIWI proteins and selected piRNAs is common to many types of cancers. We found significantly lower expression of PIWIL1 (P<0.0001) and piR-823 (P=0.0001) in tumor tissue in comparison to paired renal parenchyma. Further, we observed a progressive decrease in PIWIL1 (P=0.0228), PIWIL2 (P=0.0015), and PIWIL4 (P=0.0028) expression levels together with increasing clinical stage. PIWIL2 (P=0.0073) and PIWIL4 (P=0.0001) expression also progressively decreased with increasing Fuhrman grade. Most importantly, low-expression levels of PIWIL1 (P=0.009), PIWIL2 (P<0.0001), and PIWIL4 (P=0.0065) were significantly associated with worse overall survival in renal cell carcinoma (RCC) patients. Our results suggest the involvement of PIWIL genes and piR-823 in RCC pathogenesis, and indicate PIWIL1, PIWIL2, and PIWIL4 as potential prognostic biomarkers in patients with RCC. PMID- 26811691 TI - Overexpression of p53 activated by small activating RNA suppresses the growth of human prostate cancer cells. AB - Previous research has reported that a particular double-stranded RNA, named dsP53 285, has the capacity to induce expression of the tumor suppressor gene TP53 in chimpanzee cells by targeting its promoter. Usually, it is the wild-type p53 protein, rather than mutants, which exhibits potent cancer-inhibiting effects. In addition, nonhuman primates, such as chimpanzees, share almost identical genome sequences with humans. This prompted us to speculate whether dsP53-285 can trigger wild-type p53 protein expression in human prostate cancer (PCa) cells and consequently suppress cell growth. The human PCa cell lines LNCaP and DU145 were transfected with dsP53-285 for 72 hours. Compared with the dsControl and mock transfection groups, expression of both p53 messenger RNA and p53 protein was significantly enhanced after dsP53-285 transfection, and this enhancement was followed by upregulation of p21, which indirectly indicated that dsP53-285 induced wild-type p53 expression. Moreover, overexpression of wild-type p53 mediated by dsP53-285 downregulated the expression of Cyclin D1 and cyclin dependent kinase 4/6, thereby inducing PCa cell cycle arrest in G0/G1 phase and then inhibiting cell proliferation and clonogenicity. More importantly, dsP53-285 suppressed PCa cells mainly by modulating wild-type p53 expression. In conclusion, our study provides evidence that dsP53-285 can significantly stimulate wild-type p53 expression in the human PCa cell lines LNCaP and DU145 and can exert potent antitumor effects. PMID- 26811692 TI - Spectrum of autoimmune vesiculobullous diseases in Iran: a 13-year retrospective study. AB - BACKGROUND: Autoimmune bullous diseases (ABDs) represent a group of rare, acquired disorders characterized by overlapping features with involvement of the skin and mucous membranes, resistance to treatment, and potential lethality that comprise pemphigus, bullous pemphigoid (BP), epidermolysis bullosa, dermatitis herpetiformis, and linear immunoglobulin A bullous dermatosis. AIM: The main aim of this study was to identify the epidemiologic characteristics and clinical courses of these common diseases in Hamadan, Iran. Few surveys have been carried out to demonstrate the whole spectrum of ABDs in the literature. Notably, in Hamadan we are the first. MATERIALS AND METHODS: This 13-year retrospective study was designed to evaluate all of documented data obtained from hospitalized patients with ABDs at Farshchian Hospital from October 1999 to October 2012. We collected information on epidemiologic data, clinical aspects, histologic findings, and therapy prescribed. Data were analyzed using SPSS. RESULTS: Of 168 patients, 78% had pemphigus. The age of patients at presentation ranged from 1 month to 115 years, with a mean of 47.5+/-19.93 years. Mucosal or skin involvement of ABDs was statistically significant (P<0.001). The incidence of ABDs differed significantly based on anatomic location (P=0.003). We documented three deaths. CONCLUSION: Compared to previous literature, our findings showed equal epidemiologic properties in Iran. Although pemphigus was the most common ABD followed by BP, it is expected that in line with the global trend, an increase in BP will be driven by population aging in Iran. PMID- 26811693 TI - Cross-cultural adaption of the German Quebec Back Pain Disability Scale: an exposure-specific measurement for back pain patients. AB - STUDY DESIGN: Cross-cultural translation and psychometric testing. OBJECTIVE: The purpose of the present study was to examine reliability and validity of a cross cultural adaption of the German Quebec Back Pain Disability Scale (QBPDS) in a context of a randomized controlled trial evaluating the effectiveness of graded in vivo exposure in chronic low back pain patients. BACKGROUND: The QBPDS is one of the most widely used disease-specific disability questionnaires. In particular, for cognitive behavioral treatments with a clear focus on behavioral aspects such as graded in vivo exposure, the QBPDS provides an ascertained strategy with a sound conceptual basis and excellent quality criteria. Nevertheless, there is conflicting evidence concerning factor structure and a German adaption is missing. METHODS: The cross-cultural adaption followed international guidelines. Psychometric testing was performed using data from 180 participants with chronic low back pain. The psychometric analyses included internal consistency, convergent, and divergent validity. Exploratory factor analysis was used to determine the underlying factor structure. RESULTS: The QBPDS showed strong psychometric properties, with high internal consistency for the full scale (alpha=0.94) and good convergent and divergent validity. The factor analysis revealed a four-factor solution (bending, ambulation, brief effortful movements, and long-lasting postures). CONCLUSION: The translation and cross-cultural adaption of the QBPDS into German was successful. The German version proved to be a valid and reliable instrument and is well suited for use in the context of an exposure-based psychological treatment. PMID- 26811694 TI - Erratum: Incidence, morbidity, mortality, and prevalence of diabetes in Denmark, 2000-2011: results from the Diabetes Impact Study 2013 [Corrigendum]. AB - [This corrects the article on p. 421 in vol. 7, PMID: 26604822.]. PMID- 26811695 TI - Differences in sexual behavior, health, and history of child abuse among school students who had and had not engaged in sexual activity by the age of 18 years: a cross-sectional study. AB - BACKGROUND: Empirical research about late sexual debut and its consequences is limited, and further research is needed. OBJECTIVE: To explore how students who had not had intercourse by the age of 18 years differed in terms of sociodemographic factors, physical and psychological health, sexual behavior, and history of sexual abuse from those who had. MATERIALS AND METHODS: This is a cross-sectional survey involving 3,380 Swedish 18-year-olds. Descriptive analyses were used to investigate different types of sexual behavior. Ordinal data concerning alcohol consumption, self-esteem, sexual and physical abuse, parental relationships, sense of coherence, and health were analyzed, and multiple regression was carried out to identify the most important factors associated with no sexual debut. RESULTS: Just under a quarter of the adolescents had not had oral, anal, or vaginal sex by the age of 18 years, and they comprised the index group. They were characterized by being more likely to have caring fathers, parents born outside Europe, lower pornography consumption, lower alcohol and tobacco consumption, less antisocial behavior, and above all lower sexual desire (sometimes, adjusted odds ratio [aOR] 3.8; never/seldom, aOR 13.3) and fewer experiences of sexual abuse (aOR 25.5). Family structure and culture matters when it comes to the age of sexual debut. CONCLUSION: Adolescents with no sexual debut at 18 years of age seemed to live a more stable and cautious life than more sexual experienced peers, exemplified by fewer antisocial acts, less smoking and alcohol/drug consumption, less sexual desire, and less experience of sexual abuse. PMID- 26811696 TI - Conducting qualitative interviews by telephone: Lessons learned from a study of alcohol use among sexual minority and heterosexual women. AB - This study explored effective interviewer strategies and lessons-learned based on collection of narrative data by telephone with a sub-sample of women from a population-based survey, which included sexual minority women. Qualitative follow up, in-depth life history interviews were conducted over the telephone with 48 women who had participated in the 2009-2010 National Alcohol Survey. Questions explored the lives and experiences of women, including use of alcohol and drugs, social relationships, identity, and past traumatic experiences. Strategies for success in interviews emerged in three overarching areas: 1) cultivating rapport and maintaining connection, 2) demonstrating responsiveness to interviewee content, concerns, and 3) communicating regard for the interviewee and her contribution. Findings underscore both the viability and value of telephone interviews as a method for collecting rich narrative data on sensitive subjects among women, including women who may be marginalized. PMID- 26811697 TI - Skin microbiota of first cousins affected by psoriasis and atopic dermatitis. AB - BACKGROUND: Psoriasis and atopic dermatitis (AD) are chronic inflammatory skin diseases, which negatively influence the quality of life. In the last years, several evidences highlighted the pivotal role of skin bacteria in worsening the symptomatology of AD and psoriasis. In the present study we evaluated the skin microbiota composition in accurately selected subjects affected by (AD) and psoriasis. METHODS: Three first cousins were chosen for the study according to strict selection of criteria. One subject was affected by moderate AD, one had psoriasis and the last one was included as healthy control. Two lesional skin samples and two non-lesional skin samples (for AD and psoriatic subjects) from an area of 2 cm(2) behind the left ear were withdrawn by mean of a curette. For the healthy control, two skin samples from an area of 2 cm(2) behind the left ear were withdrawn by mean of a curette. DNA was extracted and sequencing was completed on the Ion Torrent PGM platform. Culturing of Staphylococcus aureus from skin samples was also performed. RESULTS: The psoriatic subject showed a decrease in Firmicutes abundance and an increase in Proteobacteria abundance. Moreover, an increase in Streptococcaceae, Rhodobacteraceae, Campylobacteraceae and Moraxellaceae has been observed in psoriatic subject, if compared with AD individual and control. Finally, AD individual showed a larger abundance of S. aureus than psoriatic and healthy subjects. Moreover, the microbiota composition of non-lesional skin samples belonging to AD and psoriatic individuals was very similar to the bacterial composition of skin sample belonging to the healthy control. CONCLUSION: Significant differences between the skin microbiota of psoriatic individual and healthy and AD subjects were observed. PMID- 26811698 TI - From the Editor-in-Chief. PMID- 26811699 TI - The pharmacological basis of opioids. AB - An opioid is a chemical that binds to opioid receptors, which are widely distributed in the central and peripheral nervous system and gastrointestinal tract. The different effects elicited by activation of these receptors are due to their specific neuronal and extraneuronal distribution. The painkiller effect of opioids is induced by the synergy of the two events, namely reduction of pain threshold and emotional detachment from pain. The opioid effects transcending analgesia include sedation, respiratory depression, constipation and a strong sense of euphoria. There are opioid-like substances endogenously produced by the body. Naturally occurring peptides, called enkephalins, have opioid-like activities but are not derived from opium and exert opioid-like effects by interacting with opioid receptors on cell membranes. Yet, animals do contain the same morphine precursors and metabolites as opium poppy and are able to synthesize endogenous morphine alkaloid. Experimental and clinical studies show that opioids, at doses comparable to those of endogenous opioids, can activate pronociceptive systems, leading to pain hypersensitivity and short-term tolerance, a phenomenon encountered in postoperative pain management by acute opioid administration. Whether endogenous opioids play a role in the acute pain necessary to the survival of the individual, remains an open question. PMID- 26811700 TI - Update on vitamin D: pros and cons. AB - Controversies on vitamin D currently represent a challenging topic in mineral metabolism research. In particular, current guidelines on vitamin D supplementation did not report consistent recommendation and the issue related to beneficial vs harmful effects of loading vitamin D doses did not lead to any firm universal conclusion. Finally, serum and clinical outcomes of vitamin D supplementation, particularly as far as extra-skeletal effect of the hormone, need to be further investigated. PMID- 26811701 TI - Osteogenic differentiation of adipose tissue-derived mesenchymal stem cells on nanostructured Ti6Al4V and Ti13Nb13Zr. AB - Bone tissue engineering and nanotechnology enable the design of suitable substitutes to restore and maintain the function of human bone tissues in complex fractures and other large skeletal defects. Long-term stability and functionality of prostheses depend on integration between bone cells and biocompatible implants. Human adipose tissue-derived mesenchymal stem cells (hAMSCs) have been shown to possess the same ability to differentiate into osteoblasts and to produce bone matrix of classical bone marrow derived stem cells (BMMSCs). Ti6A14V and Ti13Nb13Zr are two different biocompatible titanium alloys suitable for medical bone transplantation. Preliminary results from our Research Group demonstrated that smooth Ti6Al4V surfaces exhibit an osteoconductive action on hAMSCs, granting their differentiation into functional osteoblasts and sustaining bone matrix synthesis and calcification. The purpose of this study is to assay the ability of nanostructured Ti6Al4V and Ti13Nb13Zr alloys to preserve the growth and adhesion of hAMSCs and, mostly, to sustain and maintain their osteogenic differentiation and osteoblast activity. The overall results showed that both nanostructured titanium alloys are capable of sustaining cell adhesion and proliferation, to promote their differentiation into osteoblast lineage, and to support the activity of mature osteoblasts in terms of calcium deposition and bone extracellular matrix protein production. PMID- 26811702 TI - Serum 25-hydroxy vitamin D levels in patients with acne vulgaris and its association with disease severity. AB - BACKGROUND: Since vitamin D is a recent known immunoregulatory factor in some diseases which are addressed in immune system disorders such as SLE, [psoriasis] and others. OBJECTIVE: To determine the serum levels of 25-hydroxy vitamin D3 [25(OH)D] in patients with acne vulgaris and its association with clinical features. METHODS: This cross-sectional study was conducted over months. This study included 39 patients with acne vulgaris and 40 healthy controls. Subjects who did not use alcohol, vitamin D supplements, oral steroids or PUVA and/or NBUVB for more than three months were included. Serum 25(OH)D levels were measured. Baseline demographics, family history and comorbidities like PCO were recorded. Statistical analyses were performed using SPSS 16.0.0. RESULTS: The median concentration of 25(OH)D was 8.4 ng/mL (range: 1.4-99) in patients and 10.4 ng/mL (range: 3.1-56.7) in controls, with no statistical significant difference. PCOS was a significant predictor of the occurrence of acne vulgaris (OR=6.25; 95% CI: 1.52-25.66; p=0.01). There were no significant associations between severity of disease and serum 25(OH)D levels (rs=-0.12, p=0.45), age (rs= 0.28, p=0.09), BMI (rs=-0.12, p=0.46), age at onset of disease (rs=-0.08, p=0.63) and duration of disease (rs=-0.10, p=0.54). CONCLUSION: Based on the previous studies this is highly suspected that vitamin D would be a prominent factor in acne patients and more performances with bigger sample size could be useful to get positive results. PMID- 26811703 TI - Three-dimensional parametric mapping in quantitative micro-CT imaging of post surgery femoral head-neck samples: preliminary results. AB - Osteoporosis and pathological increased occurrence of fractures are an important public health problem. They may affect patients' quality of life and even increase mortality of osteoporotic patients, and consequently represent a heavy economic burden for national healthcare systems. The adoption of simple and inexpensive methods for mass screening of population at risk may be the key for an effective prevention. The current clinical standards of diagnosing osteoporosis and assessing the risk of an osteoporotic bone fracture include dual energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) for the measurement of bone mineral density (BMD). Micro-computed tomography (micro CT) is a tomographic imaging technique with very high resolution allowing direct quantification of cancellous bone microarchitecture. The Authors performed micro CT analysis of the femoral heads harvested from 8 patients who have undergone surgery for hip replacement for primary and secondary degenerative disease to identify possible new morphometric parameters based on the analysis of the distribution of intra-subject microarchitectural parameters through the creation of parametric images. Our results show that the micro-architectural metrics commonly used may not be sufficient for the realistic assessment of bone microarchitecture of the femoral head in patients with hip osteoarthritis. The innovative micro-CT approach considers the entire femoral head in its physiological shape with all its components like cartilage, cortical layer and trabecular region. The future use of these methods for a more detailed study of the reaction of trabecular bone for the internal fixation or prostheses would be desirable. PMID- 26811704 TI - Total hip replacement in osteoarthritis: the role of bone metabolism and its complications. AB - Osteoarthritis is one of the most common joint disorder. For treatment of hip symptomatic osteoarthritis, when conservative medical therapy has failed, total hip arthroplasty (THA) is a successful orthopaedic procedures that reduces pain and improves function and quality of life. Incidence of osteoarthritis is constantly increasing with raising life expectancy. This aging process also has led to an increasing number of patients with osteoporosis who need hip replacement for osteoarthritis. Osteoporosis have 3 major potential complications in total hip arthroplasty: perioperative fracture, an increased risk of periprosthetic fracture, and late aseptic loosening. The purpose of the present study was to examine the effects of osteoporosis on total hip replacement procedure outcome and highlight the importance of adequate study of calcium phosphorus metabolism in patient candidate for hip surgery, and the need to start a suitable therapy to recover the bone mass before surgery. Bone quality of the hip joint has become an important risk factor limiting the durability of THA. PMID- 26811705 TI - Normalization of bone mineral density after five years of treatment with strontium ranelate. AB - E.F., female, age 58, mother of 4 children and otherwise healthy, had gone into menopause when she was 42. She had received hormone replacement therapy during 8 years. Due to low bone mass she had been treated with oral alendronate during 7 years. She had a normal calcium intake in her diet and engaged in regular physical activity. She did not smoke, and drank alcohol only occasionally. Her mother had sustained a hip fracture at age 90. Bone densitometry of her lumbar spine by DXA showed a T-score of -3.0; standardized bone mineral density (sBMD) had decreased by 11% in the previous 3 years. She was advised to start treatment with strontium ranelate (SrR) 2 g/day, plus oral cholecalciferol (1,000 IU/day). Three months later serum alkaline phosphatase had increased 10%, and serum osteocalcin was 18.9 ng/ml (upper normal limit 13.7). One year later her lumbar BMD had increased by 13.5%. After five years of treatment the BMD value was normal (1.357 g/cm(2); T-score -0.3). The case presented here is noteworthy for two reasons. Firstly, the patient maintained low bone mass after several years of combined treatment with alendronate and hormone replacement; this combination usually induces greater densitometric responses than either treatment given alone. Secondly, she responded promptly and significantly to SrR in spite of the previous long exposure to alendronate. SrR is widely used for the treatment of osteoporosis. It is an effective and safe drug, provided the patients are properly selected. As shown here, it can help some patients to achieve a normal BMD. PMID- 26811706 TI - Teriparatide in the treatment of recurrent fractures in a Rett patient. AB - Rett syndrome is a common X-linked neurodevelopmental disorder caused by mutations in the MECP2 gene. Patients with Rett syndrome have a low bone mineral density and increased risk of fracture. The present case report describes a successful novel therapeutic intervention with teriparatide with one patient with Rett syndrome, after suffering from recurrent low-trauma fractures at intervals of several years. Because of the severity of bone involvement, the decision was made to treat with teriparatide and subsequently with intravenous bisphosphonate. Since the initiation of the treatment, there was an evident improvement at densitometric and QUS parameters. Furthermore, until the present, no new fractures have appeared. This is the first report in which teriparatide was administered to a subjects with Rett syndrome. In conclusion, this report has shown the effectiveness of teriparatide in the management of osteoporotic fractures in one subjects with Rett syndrome. This report provides evidence that increased knowledge of bone pathology and fracture prevention in Rett subjects is important and should be addressed in future studies. PMID- 26811707 TI - A steroid-induced bilateral avascular necrosis of the femoral head in an underage patient affected by multiple sclerosis. AB - Patients affected by Multiple Sclerosis are often treated by pulsed intravenous corticosteroids to manage acute relapses with positive outcomes. The intravenous administration is frequently associated to avascular necrosis of several bones, particularly the femur. The present report regards a case of an underage MS patient with a bilateral ANFH secondary to pulsed administrations of steroids, managed by a conservative approach on a hip, and by a novel surgical technique on the contralateral side. PMID- 26811708 TI - Multiple bony overgrowths in the mouth - report of two cases. AB - Tori and exostoses are benign bony protuberances that arise from bone surfaces in the oral cavity. The etiology of these growths has been implicated as multifactorial, but no consensus has been reached so far. These painless overgrowths seldom present as a complaint in the dental office unless functional or esthetic complications set in, and there is a fear for cancer. Here we discuss two rare cases where bony overgrowths present in the mouth were extensive and multiple. PMID- 26811709 TI - Regression of an ossifying fibroma of the tibia after a fracture involving the lesion. Possible role of the periostina. AB - Ossifying fibroma (OF) of the long bones is a benign fibro-osseous lesion typically seen in the first decade of life. OF usually progresses until the age of 10 years, but is occasionally found to regress spontaneously after puberty. The pathogenesis of OF is unknown; however, it has been suggested that the basic defect is in the periosteum. We present the radiological course of an OF of the tibia in a young patient, showing a rapid almost complete regression of the lesion after a tibial fracture at the lesion site. We postulate that the fracture induced activation of the periosteum in a growing skeleton was fundamental to the regression of the lesion. PMID- 26811710 TI - Severe hypocalcemia and life-threatening ventricular arrhytmias: case report and proposal of a diagnostic and therapeutic algorithm. AB - Hypocalcemia is frequent in the setting of endocrine disorders, bone diseases and renal failure. When hypocalcemia is severe it can predispose to life-threatening ventricular arrhythmias; in such cases a rapid admission to hospital and a prompt correction of electrolyte imbalance are needed. We report the case of an old patient suffering from renal failure that was admitted to our cardiac step-down unit because of severe hypocalcemia associated with ventricular arrhythmias. Hypocalcemia was promptly treated and an endocrinologic consult was requested for investigating the causes of this electrolyte imbalance. Our experience suggests the creation of a new synergy between cardiologists and endocrinologists that led us to build a simple and schematic algorithm for the diagnosis and treatment of hypocalcemia. PMID- 26811711 TI - Applying low-intensity pulsed ultrasounds (LIPUS) to a zoledronate-associated atypical femoral shaft fracture without cessation of zoledronate therapy for 3 years follow up: a case report. AB - Reports are increasing regarding atypical femoral fractures (AFFs) caused by minor trauma in patients using bisphosphonates (BPs) for long periods. Patients with malignant skeletal metastases potentially are at greater risk for these AFFs, especially considering the high dose and the duration of treatment with BPs. We evaluated a case of atypical femoral shaft fracture treated with an intramedullary nail in a patient treated for five years with zoledronate who had breast cancer with metastases to bone. Although bone union was achieved without cessation of zoledronate therapy by applying low-intensity pulsed ultrasounds (LIPUS), the remodeling phase of the fracture healing process was delayed. For BPs-associated AFFs, LIPUS is an alternative to parathyroid hormone (PTH) analogs such as teriparatide that are contraindicated in patients with malignant skeletal metastases. LIPUS is an effective treatment for fracture healing and may avoid the necessity to discontinue BP therapy. PMID- 26811713 TI - An atypical fracture in male patient with osteogenesis imperfecta. AB - So-called atypical fractures have been related to prolonged treatment with bisphosphonates. Although there remain unanswered questions with respect to their etiology and physiopathology, it does appear to be a causal relationship. There are many references in the literature about this problem in patients in whom these drugs have been used to treat osteoporosis, but few reports in patients who have received this therapy for the management of osteogenesis imperfecta. The Authors describe a case of a young male patient with osteogenesis imperfecta with a number of historical fractures, and who received treatment with these drugs, initially parenterally and subsequently orally, presenting as a complication of the treatment, an atypical diaphyseal femoral fracture. The characteristics of the fracture are consistent with the updated diagnostic criteria of the American Society for Bone and Mineral Research. The clinical case, its treatment, both surgically and metabolically with teriparatide, and its development over a year, are analysed. The case is notable for, on the one hand, the significance of the presence of this type of fracture in a young patient with this disease, and on the other, because of the administration of teriparatide outside its established clinical indications, with twin objectives: to improve the bone structure of the patient's underlying disease, and to counteract the harmful effects which bisphosphonates may have on this bone. PMID- 26811712 TI - Bilateral atypical femoral subtrochanteric fractures in a premenopausal patient receiving prolonged bisphosphonate therapy: evidence of severely suppressed bone turnover. AB - We report a case of bilateral atypical femoral fractures that occurred in a patient who had been taking bisphosphonate long-term. A 36-year-old premenopausal female diagnosed with systemic lupus erythematosus and dermatomyositis had been treated with glucocorticoid and alendronate (5 mg/day) to prevent glucocorticoid induced osteoporosis. She was taken to our hospital because she could not walk immediately after falling down from the standing position. A plain radiograph showed a subtrochanteric fracture of the left femur. Four months later, she fell again and sustained a contralateral subtrochanteric fracture. For each fracture, a femoral intramedullary nail was inserted. Delayed union was detected in both sides, and revision surgery with an iliac bone graft was required for implant breakage in the right side. Histomorphometric findings for the ilium revealed remarkably decreased osteoid volume with no osteoclasts and a minimally eroded surface, suggesting that bone turnover was severely suppressed. However, histology of the delayed union site revealed callus formation and some osteoclast appearance, suggesting that fracture healing was occurring. In total, it took 29 months (left) and 24 months (right) until fracture healing was achieved, showing delayed union. This case is extremely rare in that patient who presented with atypical femoral fractures in spite of her premenopausal status. The bone histomorphometric findings from this case suggest that severely suppressed bone turnover is associated with atypical femoral subtrochanteric fracture and can cause delayed union in patients treated with alendronate long-term. PMID- 26811714 TI - Spontaneous bilateral fracture neck of femur secondary to vitamin D deficiency: a case report. AB - We report a case of a patient who presented with inability to walk for 2 days which was acute in onset, with no history or preceeding trauma. On examination it was found to have stable vitals. Both lower limbs were in the flexed, abducted & externally rotated attitude, with no sensory motor deficit. Radiological investigations revealing osteoporosis and bilateral fracture neck of femur and blood investigations indicated severe vitamin D deficiency. PMID- 26811715 TI - DNA Sequence Polymorphism of the Lactate Dehydrogenase Genefrom Iranian Plasmodium vivax and Plasmodium falciparum Isolates. AB - BACKGROUND: Parasite lactate dehydrogenase (pLDH) is extensively employed as malaria rapid diagnostic tests (RDTs). Moreover, it is a well-known drug target candidate. However, the genetic diversity of this gene might influence performance of RDT kits and its drug target candidacy. This study aimed to determine polymorphism of pLDH gene from Iranian isolates of P. vivax and P. falciparum. METHODS: Genomic DNA was extracted from whole blood of microscopically confirmed P. vivax and P. falciparum infected patients. pLDH gene of P. falciparum and P. vivax was amplified using conventional PCR from 43 symptomatic malaria patients from Sistan and Baluchistan Province, Southeast Iran from 2012 to 2013. RESULTS: Sequence analysis of 15 P. vivax LDH showed fourteen had 100% identity with P. vivax Sal-1 and Belem strains. Two nucleotide substitutions were detected with only one resulted in amino acid change. Analysis of P. falciparum LDH sequences showed six of the seven sequences had 100% homology with P. falciparum 3D7 and Mzr-1. Moreover, PfLDH displayed three nucleotide changes that resulted in changing only one amino acid. PvLDH and PfLDH showed 75%-76% nucleotide and 90.4%-90.76% amino acid homology. CONCLUSION: pLDH gene from Iranian P. falciparum and P. vivax isolates displayed 98.8-100% homology with 1-3 nucleotide substitutions. This indicated this gene was relatively conserved. Additional studies can be done weather this genetic variation can influence the performance of pLDH based RDTs or not. PMID- 26811716 TI - Serological study of Human Fasciolosis in Patients Referring to the School of Public Health, Tehran University of Medical Sciences, Tehran, Iran during 2008 2014. AB - BACKGROUND: Fascioliasis is a zoonotic disease of livestock and human caused by Fasciola species. Here in, the results of serological evaluation of fascioliasis in people referring to the School of Public Health, Tehran University of Medical Sciences during 2008-2014 are presented. METHODS: Demographic characterizations, symptoms and eosinophil rate were registered for every patient. Using somatic antigen of Fasciola, ELISA was performed and the results were analyzed. Data of questioners were analyzed as well. RESULTS: Among 206 applicants, 24.8% were seropositive for fascioliasis, included 21% female and 28.3% male. Mean range of age of patients was between 13 to 67 yr. The highest rate of seropositivity was found among 20-30 yr old patients. Most of the patients had hypereosinophilia. All patients had history of eating raw vegetables, or drinking unsafe water. Patients were referring from different provinces of Iran, including Gilan, Mazandaran, Tehran, Ardabil, Khuzestan, Lorestan, North Khorasan, Kermanshah, Azerbaijan, Fars, Kordestan, Hamedan and Markazi. CONCLUSION: During recent years, variety of provinces in Iran, where patients with fascioliasis are referred, has been increased. Patients coming from Gilan and Mazandaran provinces were referred early after the onset of their symptoms. Most probably, physicians in Gilan and Mazandaran are more alert on fascioliasis than other provinces. Previous wrong diagnosis was more common among patients referring from other provinces than Gilan and Mazandaran provinces. PMID- 26811717 TI - Morphological and Molecular Survey of Naegleria spp. in Water Bodies Used for Recreational Purposes in Rasht city, Northern Iran. AB - BACKGROUND: Naegleria spp. is a free-living amoeba of which some species including N. fowleri and N. australeinsis are highly pathogenic in human and animals. These widespread amoebae could be found in different environmental sources particularly in aquatic resources of tropical and subtropical regions. The most important source of infection is via recreational water contact. Due to the lack of thorough research regarding species of Naegleria spp. in aquatic sources, the present study was conducted. METHODS: In the present study, 60 samples were collected from recreational water resources of Rasht city, Guilan province, north of Iran. After filtering and culturing the samples, plates were examined by microscopic method and according to the page criteria. DNA of vahlkampfiid-positive samples were then extracted using phenol-chlorophorm method. Amoebae genus was identified by targeting the ITS-region and sequencing based-approaches. RESULTS: Nine (15%) samples out of a 60 total samples were positive for Naegleria spp. of which seven belonged to potentially pathogenic N. australiensis. Two other strains were belonged to non-pathogenic N. pagei. CONCLUSION: The present research was the first report of occurrence of N. australiensis and N. pagei in Rasht city, north Iran. This study reflects the occurrence of Naegleria spp. in water sources of Guilan Province, Iran. PMID- 26811718 TI - Comparison of the Proteome Profiling of Iranian isolates of Leishmania tropica, L. major and L. infantum by Two-Dimensional Electrophoresis (2-DE) and Mass spectrometry. AB - BACKGROUND: The mechanisms of virulence and species differences of Leishmania parasites are under the influence of gene expression regulations at posttranscriptional stages. In Iran, L. major and L. tropica are known as principal agents of cutaneous leishmaniasis, while L. infantum causes visceral leishmaniasis. METHODS: As a preliminary study, we compared the proteome mapping of the above three Iranian isolates of Leishmania species through the 2-dimension electrophoresis (2-DE), and identified the prominent proteins by Liquid Chromatography (LC) mass spectrometry. RESULTS: We reproducibly detected about 700 protein spots in each species by using the Melanie software. Totally, 264 proteins exhibited significant changes among 3 species. Forty nine protein spots identified in both L. tropica and L. major were similar in position in the gel, whereas only 35 of L. major proteins and 10 of L. tropica proteins were matched with those of L. infantum. Having identified 24 proteins in the three species, we sought to provide possible explanations for their differential expression patterns and discuss their relevance to cell biology. CONCLUSION: The comparison of proteome profiling pattern of the 3 species identified limit up and limit down regulated or absent /present proteins. In addition, the LC-MS data analysis showed that most of the protein spots with differential abundance in the 3 species are involved in cell motility and cytoskeleton, cell signaling and vesicular trafficking, intracellular survival / proteolysis, oxidative stress defense, protein synthesis, protein ubiquitination / proteolysis, and stress related proteins. Differentially proteins distributed among the species maybe implicated in host pathogenecity interactions and parasite tropism to cutaneous or visceral tissue macrophages. PMID- 26811719 TI - Pathogenic Free-Living Amoebae Isolated From Contact Lenses of Keratitis Patients. AB - BACKGROUND: Free-living amoeba (FLA)-related keratitis is a progressive infection of the cornea with poor prognosis. The present study aimed to investigates the contact lenses of patients with keratitis for pathogenic free-living amoebae. METHODS: Overall, 62 contact lenses and their paraphernalia of patients with keratitis cultured and tested for the presence of free-living amoebae using morphological criteria. Unusual plates including plates containing mix amoebae and Vermamoeba were submitted to molecular analysis. RESULTS: Out of 62 plates, 11 revealed the outgrowth of free living amoeba of which 9 were Acanthamoeba, one plates contained mix amoebae including Acanthamoeba and Vermamoeba and one showed the presence of Vermamoeba. These two latter plates belonged to patients suffered from unilateral keratitis due to the misused of soft contact lenses. One of the patients had mix infection of Acanthamoeba (T4) and V. vermiformis meanwhile the other patient was infected with the V. vermiformis. CONCLUSION: Amoebic keratitis continues to rise in Iran and worldwide. To date, various genera of free-living amoebae such as Vermamoeba could be the causative agent of keratitis. Soft contact lens wearers are the most affected patients in the country, thus awareness of high-risk people for preventing free-living amoebae related keratitis is of utmost importance. PMID- 26811720 TI - Diagnosing Malaria Cases Referred to the Malaria Reference Laboratory in Tehran University of Medical Science, Iran. AB - BACKGROUND: The number of malaria cases is declining worldwide; however, it remains as a serious health problem. Diagnosing unusual cases is the most important issue to manage the problem. This study designed to describe the number of falciparum and vivax malaria infected patients referred to Malaria Reference Laboratory in Tehran University of Medical Science from 2000 to 2012. METHODS: A retrospective study was conducted based on the collected questionnaires from each patient referred to the laboratory. Diagnosing results and demographic information for positive cases were analyzed using SPSS software. Problematic cases were evaluated for any difficulties in diagnosis or in clinical signs. Scanning and molecular methods were performed whenever there was an atypical case referred to the laboratory. Some of the samples had various difficulties for diagnosing such as presence of fussed gametocytes and schizonts of Plasmodium falciparum in peripheral blood and CCHF like hemoragic disorders. RESULTS: Plasmodium vivax caused a large proportion of the cases (76.1%) in contrast with P. falciparum that included smaller proportion (22.8%) and the rest (1.1) belonged to mixed infection. Most of the positive cases (69.6%) were belonged to Afghani people. Men (94.6%) showed more infection than women (5.4%), moreover the most infection (44.5%) was seen at a range of 21-30 yr. CONCLUSION: In the case of existing atypical issues to diagnose, it is needed to perform more precise microscopical examination beyond the current standard conditions. Sometimes molecular method is required to verify the exact agent of the disease. PMID- 26811721 TI - Recombinant LPG3 Stimulates IFN-Gamma and TNF-A Secretion by Human NK Cells. AB - BACKGROUND: Natural killer (NK) cells play an important role in early stages of innate immune responses against viral and tumoral attacks. Activation of NK cells by leishmaniasis results in secretion of cytokines such as interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, which enhances the phagocytosis and clearance of parasite. Lipophosphoglycan 3 (LPG3), the Leishmania homologous with GRP94 (glucose regulated protein 94), a member of HSP90 family, contributes to LPG assembly as the most abundant macromolecule on the surface of Leishmania promastigotes. METHODS: We purified NK cells from healthy individuals (n=10) using magnetic-activated cell sorting (MACS) technology. Purified NK cells were co-incubated with different concentrations of recombinant LPG3 (rLPG3), and its N terminal (NT) and C-terminal (CT) fragments. Finally, the production of IFN-gamma and TNF-alpha by NK cells were measured by ELISA. RESULTS: Recombinant LPG3 but not its fragments (CT and NT), can significantly enhance the production of TNF alpha by NK cells (P<0.05). Moreover, rLPG3, CT, and NT fragments were markedly stimulated the secretion of IFN-gamma by NK cells (P<0.001). CONCLUSION: The Leishmania LPG3 antigen can effectively activate NK cells, in vitro. Leishmania LPG3 participates in the innate immunity against leishmaniasis and thereby improves the effective parasite destruction. However, its efficiency should be tested in vivo. PMID- 26811722 TI - Encephalitozoon cuniculi infection among immunocompromised and immunocompetent humans in Egypt. AB - BACKGROUND: Encephalitozoon cuniculi infects a wide range of homoeothermic animals, including man. Complications due to this microsporidian have been reported only in immunocompromised patients. Reports on E. cuniculi in immunocompetent humans are lacking, most probably, because it is not linked to any clinical manifestations in such hosts. The present work was carried out with the aim of studying, for the first time in Egypt, the prevalence of E. cuniculi infection of urinary tract among non-HIV immunocompromised patients and immunocompetent individuals. It tested also the influence of some factors on the risk of infection. METHODS: Blood and urine samples were collected from 88 persons (44 non-HIV immunocompromised patients and 44 subjects as immunocompetent control group). IFAT serological assay and Weber's green modified trichrome stain (MTS) urine smears were carried out. Molecular study by PCR was also performed to detect DNA of E. cuniculi in urine samples. A full history sheet was fulfilled for each subject to test the suspected risk factors. RESULTS: The IFAT examination confirmed the presence of antibodies against E. cuniculi in 44.3% of the human subjects. The seroprevalence of E. cuniculi was significantly higher in the immunocompromised patients compared with the immunocompetent individuals (77.3% versus 11.4%). Compared with IFAT (the gold standard), the sensitivity and specificity of Weber's green MTS smears were 69.23% and 89.80%. By using PCR, no positive cases were detected among human subjects. CONCLUSION: A high prevalence of E. cuniculi infection in the studied individuals was noted. Although infection was found in some immunocompetent individuals, the immune status of the host remains the corner stone for occurrence of the infection. PMID- 26811723 TI - Comparison of Parasite Burden Using Real-Time Polymerase Chain Reaction Assay and Limiting Dilution Assay in Leishmania major Infected Mouse. AB - BACKGROUND: Limiting dilution assay is considered as the gold standard method for quantifying the number of parasites in the animal model of Leishmania infection. Nowadays, real-time PCR is being increasingly applied to quantify infectious agents. In the present study, a real-time PCR assay was developed to estimate parasite burdens in lymph nodes of Leishmania major infected BALB/C mice. Enumeration of parasites was also performed by limiting dilution assay and compared with the results of real-time PCR based quantification. METHODS: The SYBR Green based real-time PCR assay was performed to amplify a 75 bp fragment of superoxide dismutase B1 gene in the lymph nodes of L. major infected BALB/C mice 8 weeks post infection. Mice were infected subcutaneously at the base of their tail with 2 * 10(5) L. major promastigotes in the stationary phase of growth. To compare parasite burdens obtained by real-time PCR assay with those of limiting dilution assay, twelve 8-fold serial dilutions of the lymph node homogenates were prepared in the Schneider medium and incubated at 26 degrees C. After 7 days, wells containing motile parasites were identified by direct observation under an inverted light microscope and the total number of parasites was estimated using the ELIDA software. RESULTS: Spearman's correlation coefficient of the parasite burdens between real-time PCR and limiting dilution assay was 0.72 (P value = 0.008). CONCLUSION: Real-time PCR assay is an appropriate replacement to existing limiting dilution assay in quantifying parasite burden in the experimental model of Leishmania infection. PMID- 26811724 TI - The Potential of beta Carbolin Alkaloids to Hinder Growth and Reverse Chloroquine Resistance in Plasmodium falciparum. AB - BACKGROUND: Nowadays, scourge of malaria as a fatalistic disease has increased due to emergence of drug resistance and tolerance among different strains of Plasmodium falciparum. Emergence of chloroquine (CQ) resistance has worsened the calamity as CQ is still considered the most efficient, safe and cost effective drug among other antimalarials. This urged the scientists to search for other alternatives or sensitizers that may be able to augment CQ action and reverse its resistance. METHOD: Three beta-carbolin derivatives, namely, harmalin, harmol and harmalol were tested for their anti-plasmodial and CQ resistance reversal effects against P. falciparum 3D7 and K1. SYBRE Green-1 based drug sensitivity assay and isobologram analysis were used to screen the mentioned effects respectively. RESULTS: All of them showed moderate anti-plasmodium effect and harmalin was the most effective as compared to the others in reversing CQ resistance and tolerance. CONCLUSION: The mentioned phytochemicals are not ideal to be used as conventional antimalarials and only harmalin can be suggested to reverse CQ resistance in P. falciparum K1. PMID- 26811725 TI - High Seroprevalence of Toxoplasma gondii Antibody in HIV/AIDS Individuals from North of Iran. AB - BACKGROUND: Toxoplasmosis in immunocompetent people is generally asymptomatic but in immunocompromised patients including HIV/AIDS, cancer patients, and organ transplant recipients, etc. it can lead to serious pathological problems. The objective of current study was to determine the seroprevalence of T. gondii IgG and IgM antibodies in HIV/AIDS patients using ELISA technique in Mazandaran Province, northern Iran. METHODS: Overall, 82 serum samples (61 males and 21 females) were collected from HIV/AIDS patients in Mazandaran Provinces, in 2013. Sera were surveyed employing ELISA assay. Data were analyzed using Chi-Square or Fisher exact test. In addition, before sampling a questionnaire was filled out for each subject. RESULTS: Overall seroprevalence of examined sera was 96.3% for IgG antibody but none of the sera shown IgM antibody against T. gondii. The seroprevalence of toxoplasmosis in males and females was 96.7% and 95.2%, respectively. An antibody titer of >1 IU/ml was considered as positive. Furthermore, none of the included variables statistically was significant. CONCLUSIONS: Seroprevalence of chronic (latent) toxoplasmosis in HIV/AIDS patients in Mazandaran Province is high compared to toxoplasmosis in general population. Consequently, the risk of acquiring Toxoplasma encephalitis in examined seropositive HIV/AIDS patients of Toxoplasma is high. PMID- 26811726 TI - Evaluation of Immunogenicity of Cocktail DNA Vaccine Containing Plasmids Encoding Complete GRA5, SAG1, and ROP2 Antigens of Toxoplasma gondii in BALB/C Mice. AB - BACKGROUND: Severe and fatal complications of toxoplasmosis urge development of effective vaccines against the disease. The current study was performed to evaluate cocktail DNA vaccine containing plasmids encoding GRA5, SAG1, and ROP2 genes of Toxoplasma gondii in BALB/c mice in Tarbiat Modares University in 2012. METHODS: The plasmids containing complete GRA5, SAG1, and ROP2 genes were mass extracted and then the recombinant plasmids were administered via intramuscular injections according to immunized mice three times with three-week intervals. Then splenocytes were cultured, and proliferation as well as cytokine assays were carried out. The other mice in each group were inoculated by the parasite and mortality of the mice was evaluated on a daily basis. RESULTS: The results of cytokine assay for INF-gamma were higher in the mice that received the cocktail DNA containing recombinant plasmids. Evaluation of proliferation of splenocytes using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay indicated induction of cellular response. Measurement of total IgG and the isotypes of IgG1 and IgG2a showed that the cocktail DNA stimulated IgG and IgG2a production in comparison with the control groups (P<0.05). Furthermore, the survival rate of mice in the groups that received the cocktail DNA was significantly higher than that in the control groups (P<0.05). CONCLUSION: Administration of the cocktail DNA vaccine led to production of higher levels of IFN-gamma, confirmed by secretion of IgG2a, and the immune response was shifted toward Th1. Thus, the cocktail DNA containing the recombinant plasmids can be an appropriate candidate for immunization against toxoplasmosis. PMID- 26811727 TI - Utility of Western Blot Analysis for the Diagnosis of Cutaneous Leishmaniasis. AB - BACKGROUND: Cutaneous leishmaniasis (CL) is a parasitic disease with a relatively wide distribution in different areas of the world, including Iran. The parasite is mainly diagnosed microscopically, but serological approaches might be useful for diagnosis as well. This study aimed to assess the efficacy of an immunoblotting system for serodiagnosis of cutaneous leishmaniasis in Iran. METHODS: Sixty-one sera samples from parasitologically confirmed CL patients and 50 sera samples from healthy controls along with 50 sera sample from non-CL patients were collected. Native strain of Leishmania major was cultured in Schneider medium and soluble Leishmania antigens were prepared from amastigotes like parasites. All of sera samples were evaluated by an immunoblotting system. RESULTS: Components of 14 to 135 kDa were detectable by the sera of CL patients. From 61 sera of CL patients, 59 cases (96.7%) detected a 63 kDa subunit and 51 cases (83.6%) recognized a 32-35 kDa component. Among all subunits, the 63 kDa band showed the highest sensitivity (96.7%) and a 75 kDa band had the highest (98%) specificity. CONCLUSION: Immunoblotting has a satisfactory performance in diagnosis of CL and this test can be used, as an aid, for proper diagnosis of CL. PMID- 26811728 TI - Description of Pallisentis (Brevitritospinus) punctati n. sp. (Acanthocephala: Quadrigyridae) from Channa punctatus in Bareilly, Uttar Pradesh, India. AB - BACKGROUND: The genus Pallisentis is an endoparasitic acanthocephalan inhabiting the intestinal walls. Hooks and spines of the worm are significant taxonomical and adaptive tools. METHODS: The parasites were fixed, dehydrated and examined under Olympus BX 53 Microscope with DIC attachment, digital camera and CELLSENS imaging system [Light microscopy (LM)] and fixed in 2% glutaraldehyde in 0.1 M cacodylate buffer, dehydrated, rotary-coated with gold palladium in NeoCoater 100 240V and examined in Neo JCM-6000 [scanning electron microscopy (SEM)]. RESULTS: P. punctati n. sp. (prevalence 65.51%; mean intensity 3-6 par/host) is described. Females almost twice as large as males; proboscis hooks small; collar spine rows similar [16] and constant in both sexes but number of spines per row greater in females [22] than males [14]; trunk spine rows 28-39 (spines per row 14-18) in females and 20-26 (spines per row 10-12) in males. spine length of females almost twice as long as males, spines extend up to posterior testis in males and 3/4 of total body length in females, Saefftigen's pouch present, nuclei in cement gland 10-11, seminal vesicle, bursa and egg size small. SEM indicated lack of micro sculptures, and spines embedded on pre-trunk and trunk. Sex-based differences apparent (hook sizes, greater number of spines per row and longer spines in pre trunk and trunk of females). Male trunk spine was narrower and of lateral spine with characteristic hooked appearance. CONCLUSION: A new species of Pallisentis based on LM and SEM is described, sexual diversity in hook and spine structure is reported. PMID- 26811729 TI - Development of a Double Glass Mounting Method Using Formaldehyde Alcohol Azocarmine Lactophenol (FAAL) and its Evaluation for Permanent Mounting of Small Nematodes. AB - BACKGROUND: Permanent slide preparation of nematodes especially small ones is time consuming, difficult and they become scarious margins. Regarding this problem, a modified double glass mounting method was developed and compared with classic method. METHODS: A total of 209 nematode samples from human and animal origin were fixed and stained with Formaldehyde Alcohol Azocarmine Lactophenol (FAAL) followed by double glass mounting and classic dehydration method using Canada balsam as their mounting media. The slides were evaluated in different dates and times, more than four years. Different photos were made with different magnification during the evaluation time. RESULTS: The double glass mounting method was stable during this time and comparable with classic method. There were no changes in morphologic structures of nematodes using double glass mounting method with well-defined and clear differentiation between different organs of nematodes in this method. CONCLUSION: Using this method is cost effective and fast for mounting of small nematodes comparing to classic method. PMID- 26811730 TI - Efficacy of the Bunium persicum (Boiss) Essential Oil against Acute Toxoplasmosis in Mice Model. AB - BACKGROUND: We evaluated the in vivo activity of Bunium persicum (Boiss) essential oil on infected mice with acute toxoplasmosis. METHODS: To evaluate prophylactic effects, male NMRI mice received B. persicum essential oil at the concentrations of 0.05 and 0.1 mL/kg for 14 days. After 24 h mice were infected intraperitonealy with 1*10(4) tachyzoites of T. gondii, RH strain. In order to investigate therapeutic effects, mice were infected and then received B. persicum oil at the concentrations of 0.05 and 0.1 ml/kg two times a day for 5 days. The time/mean time of death in all infected mice and the number of tachyzoites from infected mice were recorded. RESULTS: The time/mean time of death of infected mice was 8 and 9 days after oral administration of B. persicum oil at the concentration of 0.05 and 0.1 mL/kg, respectively (P<0.05). In contrast, the time/mean time of death control group was 5 days. In addition, B. persicum significantly reduced the mean number of tachyzoites compared with control group. The time/mean time of death of infected mice was 6 and 7 days after oral administration of B. persicum essential oil at the concentration of 0.05 and 0.1 mL/kg, respectively. In contrast, the time/mean time of death control group was 5 days. B. persicum especially at the concentration of 0.1 ml/kg significantly reduced the mean number of tachyzoites compared with control group. CONCLUSION: The results showed the potential of B. persicum essential oil as a natural source for the production of new prophylactic agent for use in toxoplasmosis. PMID- 26811731 TI - Seroepidemiology of Toxocariasis in Children (5-15 yr Old) Referred to the Pediatric Clinic of Imam Hossein Hospital, Isfahan, Iran. AB - BACKGROUND: Human toxocariasis, a helminthozoonosis, is due to the migration of Toxocara species larvae into human organisms. Humans, especially children become infected by ingesting of embryonated eggs from soil, dirty hands, and raw vegetables. Seroprevalence of this infection is high in developed countries, especially in rural areas. The aim of this study was to investigate the seroepidemiology of Toxocariasis in children referred to the pediatric clinic of Imam Hossein hospital, Isfahan, Iran. METHODS: In this cross sectional study the sera of children aged 5 to 15 years old, admitted to Imam Hossein Pediatric Hospital were collected during 2013-14. Then the sera were examined for anti Toxocara canis antibodies using commercial ELISA kit. RESULTS: From 427 children, 196 (45.9%) were female and 231(54.1%) were male. 107(25.1%) were from rural and 320 (74.9%) were from urban area. Of them 129 (30.2%) were contacted with dog. One child (0.2%) had hypereosinophilia, 33 (7.7%) eosinophlia, and 6 (1.39%) were positive for T. canis IgG (two male and four female). Four of infected children with T. canis were from urban (1.25%) and two from rural areas (1.9%). There was no significant correlation between education of parents, gender, age, place of living and contact with dog with ELISA results test. CONCLUSION: Toxocariasis is prevalent in the children of Isfahan region. Results suggest a low Toxocara exposure in children in this area. Therefore, more risk factors associated with Toxocara exposure should be identified in the further investigation. PMID- 26811732 TI - Resistance and Susceptibility to Malarial Infection: A Host Defense Strategy against Malaria. AB - BACKGROUND: In an effort to understand what limits the virulence of malaria parasites in relation to the host genetic and immunogenic background, we investigated the possibility that the parasite and host genotype crossover interactions constrain virulence. METHODS: Two groups of mice from different genotypes were used (C57BL/6 (B6) and DBA/2 mice). The mice were infected with a virulent parasite line Plasmodium yoelii 17XL (P. yoelii 17XL). Parasitemia, hematocrit value and lymphocytes yielded by livers and spleens were evaluated. Fluorescence Activated Cell Sorting (FACS) analysis illustrated phenotypic characterization of lymphocytes. RESULTS: Infection with P. yoelii 17XL did not result in the death of DBA/2 mice. In contrast, B6 mice developed significantly high parasitemia and succumbed to death. Using (FACS) analysis, DBA/2 mice were found to experience a marked expansion of interleukin (IL)-2Rbeta(+) CD3(int) cells and gammadelta T cells in the liver, especially in the recovery phase. The expansion of unconventional T cells (i.e. B220(+) T cells) was also marked in DBA/2 mice. CONCLUSION: The outcome of murine malaria infections depends on the dynamic interplay between the immune-mediator and the genotype of the host. PMID- 26811733 TI - Seroprevalence and Risk Factors of Toxoplasma gondii Infection in Buffaloes, Sheep and Goats in Yunnan Province, Southwestern China. AB - BACKGROUND: The seroprevalence of Toxoplasma gondii infection in buffaloes, sheep and goats in Yunnan Province, southwestern China was conducted between May 2012 and December 2013. METHODS: A total of 973 (427 buffaloes, 154 sheep and 392 goats) serum samples were collected from seven administrative regions of Yunnan Province, and examined for T. gondii antibodies by indirect hemagglutination (IHA) test. Some risk factors related to species, age, gender and geographical origin were determined using a multinomial logistic regression. RESULTS: The overall seroprevalence of T. gondii in ruminant species was estimated at 11.9%. The final logistic regression model demonstrated that host species and geographical origin were the main risk factors associated with T. gondii infection (P<0.05). CONCLUSION: Taken together, the results of the present study revealed a high exposure to T. gondii in ruminant species in Yunnan Province, which has an important implication for public health. PMID- 26811734 TI - Prevalence of Intestinal Parasites among Food-handlers in Shiraz, Iran. AB - BACKGROUND: Parasitic intestinal infections are still among socioeconomic problems in the world, especially in developing countries like Iran. Food handlers that directly deal with production and distribution of foods between societies are one of the most important sources to transmit parasitic infections to humans. The aim of this study was to determine the prevalence of intestinal parasitic infections among food-handlers in Shiraz, Iran. METHODS: In this cross sectional study, 1021 feces samples were randomly collected from food-handlers in Shiraz, central Iran from August to September 2013. Two different methods, routine direct fecal examination and Formalin -Ethyl acetate concentration as a complementary technique, were done to detect parasites. RESULTS: The prevalence of parasitic organisms was 10.4% in the food-handlers. The most species of the protozoan parasites were G. lamblia, E. coli and B. hominis; meanwhile, only one infection by H. nana (0.1%) was detected in this group. Mixed infections were observed in 13.2% (n=14/106) of positive cases. The majority of participants were male (57%); however, data analysis showed significant statistical difference in the rate of infection between females 11.9% (n=53/444) and males 9% (n=52/577) (P=0. 024). There was no significant statistical difference in the rate of infection among different educational and occupation groups. CONCLUSION: Although decreasing of helminthic infections is distinct, but infecting with protozoan parasites is still important in food-handlers. Concentration technique is more useful than direct smear technique, especially for detection parasites in low number. High level of education in our study showed that training courses in this group could be effective in the implementation of control and prevention programs. PMID- 26811735 TI - Human Hydatidosis/Echinococosis in North Eastern Iran from 2003-2012. AB - BACKGROUND: Human cystic echinococcosis (hydatidosis) continues to be an essential cause of morbidity and mortality in many parts of the world. METHODS: We studied hydatid cyst pattern in hospitalized adult patients from 2003 to 2012 in Mashhad and Neyshabour, northeast of Iran. RESULTS: Overall, 1342 patients, 711 females (53%) and 631 males (47%) diagnosed as infected with hydatid cyst were evaluated. Their age was between 1 and 91 yr (mean age 37.75). The most affected age group was 20-30 yr old. Totally, 953 cases (71%) were urban and 375 cases (27.8%) were rural residents. The most common localization of cysts was the liver and lung. The housewives were the most frequently infected occupations. CONCLUSION: The rate of infection with hydatid cyst is high in Mashhad, northeast of Iran, and the incidence of human hydatidosis tends to increase in recent years so control and prevention programs are recommended. PMID- 26811736 TI - Genetic Characterization of Toxoplasma gondii from Zoo Wildlife and Pet Birds in Fujian, China. AB - BACKGROUND: Toxoplasmosis, a worldwide zoonotic disease, is caused by Toxoplasma gondii. The distribution of genetic diversity of T. gondii in wild animals is of great importance to understand the transmission of the parasite in the environment. However, little is known about T. gondii prevalence in wild animals and birds in China. METHODS: We conducted the genetic characterization of T. gondii isolated from Zoo Wild Animals and Pet Birds in Fujian Province, Southeastern China. Heart tissues were collected from 45 zoo animals and 140 pet birds. After identified using B1 gene, the genetic diversity of T. gondii isolates were typed at 11 genetic markers, including SAG1, 5' and 3'-SAG2, alternative SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, Apico, and CS3. RESULTS: Seven of 45 zoo animals and 3 of 140 pet birds were positive by PCR amplification using T. gondii B1 gene specific primers. Of these positive isolates, 3 isolates from Black-capped (Cebus apella), Peacock (Peafowl) and Budgerigar (Melopsittacus undulatus) were successfully genotyped at 11 genetic loci, and grouped to three distinct genotypes: ToxoDB Genotype #9, #2 and #10, respectively. CONCLUSION: This is the first genotyping of T. gondii isolated from zoo wild animals and pet birds in Fujian, China. There is a potential risk for the transmission of this parasite through zoo wild animals and pet birds in this region. PMID- 26811737 TI - Clarification on a Published Paper in Iran J Parasitol. PMID- 26811738 TI - Highly efficient lipid production in the green alga Parachlorella kessleri: draft genome and transcriptome endorsed by whole-cell 3D ultrastructure. AB - BACKGROUND: Algae have attracted attention as sustainable producers of lipid containing biomass for food, animal feed, and for biofuels. Parachlorella kessleri, a unicellular green alga belonging to the class Trebouxiophyceae, achieves very high biomass, lipid, and starch productivity levels. However, further biotechnological exploitation has been hampered by a lack of genomic information. RESULTS: Here, we sequenced the whole genome and transcriptome, and analyzed the behavior of P. kessleri NIES-2152 under lipid production-inducing conditions. The assembly includes 13,057 protein-coding genes in a 62.5-Mbp nuclear genome. Under conditions of sulfur deprivation, lipid accumulation was correlated with the transcriptomic induction of enzymes involved in sulfur metabolism, triacylglycerol (TAG) synthesis, autophagy, and remodeling of light harvesting complexes. CONCLUSIONS: Three-dimensional transmission electron microscopy (3D-TEM) revealed extensive alterations in cellular anatomy accompanying lipid hyperaccumulation. The present 3D-TEM results, together with transcriptomic data support the finding that upregulation of TAG synthesis and autophagy are potential key mediators of the hyperaccumulation of lipids under conditions of nutrient stress. PMID- 26811739 TI - Phylogenomic analysis reveals genome-wide purifying selection on TBE transposons in the ciliate Oxytricha. AB - BACKGROUND: Transposable elements are a major player contributing to genetic variation and shaping genome evolution. Multiple independent transposon domestication events have occurred in ciliates, recruiting transposases to key roles in cellular processes. In the ciliate Oxytricha trifallax, the telomere bearing elements (TBE), a Tc1/mariner transposon, occupy a significant portion of the germline genome and are involved in programmed genome rearrangements that produce a transcriptionally active somatic nucleus from a copy of the germline nucleus during development. RESULTS: Here we provide a thorough characterization of the distribution and sequences of TBE transposons in the Oxytricha germline genome. We annotate more than 10,000 complete and 24,000 partial TBE sequences. TBEs cluster into four major families and display a preference for either insertion into DNA segments that are retained in the somatic genome or their maintenance at such sites. The three TBE-encoded genes in all four families display dN/dS ratios much lower than 1, suggesting genome-wide purifying selection. We also identify TBE homologs in other ciliate species for phylogenomic analysis. CONCLUSIONS: This paper provides genome-wide characterization of a major class of ciliate transposons. Phylogenomic analysis reveals selective constraints on transposon-encoded genes, shedding light on the evolution and domesticated functions of these transposons. PMID- 26811740 TI - Florivory and nectar-robbing perforations in flowers of pointleaf manzanita Arctostaphylos pungens (Ericaceae) and their effects on plant reproductive success. AB - Damage to petals may have varying effects on the reproductive success of the plant. The variation may depend on the kind of damage to the corolla. Whether the damage is limited to the corolla, as is usually the case with nectar-robbing perforations, or extending to the reproductive parts of the flower, as in the case of florivory holes, might determine the extent of the effect on the plant's reproduction. We examined the various perforations in the flowers of Arctostaphylos pungens and correlated their presence with fruiting success. We found that though florivory holes were highly associated with damage to reproductive parts, fruiting success did not differ significantly between flowers with the two kinds of damage. Although nectar-robbing perforations were not associated with reduced number of fruit produced, they were significantly correlated with reduced number of fruit that contained seemingly viable seeds. The implications of our findings are discussed in the context of pollination and antagonism. PMID- 26811741 TI - Molecular Basis for Resistance Against Phosphonate Antibiotics and Herbicides. AB - Research in recent years have illuminated data on the mechanisms and targets of phosphonic acid antibiotics and herbicides, including fosfomycin, glyphosate, fosmidomycin and FR900098. Here we review the current state of knowledge of the structural and biochemical characterization of resistance mechanisms against these bioactive natural products. Advances in the understanding of these resistance determinants have spurred knowledge-based campaigns aimed towards the design of derivatives that retain biological activity but are less prone to tolerance. PMID- 26811742 TI - Arginine-linked neomycin B dimers: synthesis, rRNA binding, and resistance enzyme activity. AB - The nucleotides comprising the ribosomal decoding center are highly conserved, as they are important for maintaining translational fidelity. The bacterial A-site has a small base variation as compared with the human analogue, allowing aminoglycoside (AG) antibiotics to selectively bind within this region of the ribosome and negatively affect microbial protein synthesis. Here, by using a fluorescence displacement screening assay, we demonstrate that neomycin B (NEO) dimers connected by L-arginine-containing linkers of varying length and composition bind with higher affinity to model A-site RNAs compared to NEO, with IC50 values ranging from ~40-70 nM, and that a certain range of linker lengths demonstrates a clear preference for the bacterial A-site RNA over the human analogue. Furthermore, AG-modifying enzymes (AMEs), such as AG O phosphotransferases, which are responsible for conferring antibiotic resistance in many types of infectious bacteria, demonstrate markedly reduced activity against several of the L-arginine-linked NEO dimers in vitro. The antimicrobial activity of these dimers against several bacterial strains is weaker than that of the parent NEO. PMID- 26811744 TI - Impacts of temperature on giant panda habitat in the north Minshan Mountains. AB - Understanding the impacts of meteorological factors on giant pandas is necessary for future conservation measures in response to global climate change. We integrated temperature data with three main habitat parameters (elevation, vegetation type, and bamboo species) to evaluate the influence of climate change on giant panda habitat in the northern Minshan Mountains using a habitat assessment model. Our study shows that temperature (relative importance = 25.1%) was the second most important variable influencing giant panda habitat excepting the elevation. There was a significant negative correlation between temperature and panda presence (rho = -0.133, P < 0.05), and the temperature range preferred by giant pandas within the study area was 18-21 degrees C, followed by 15-17 degrees C and 22-24 degrees C. The overall suitability of giant panda habitats will increase by 2.7%, however, it showed a opposite variation patterns between the eastern and northwestern region of the study area. Suitable and subsuitable habitats in the northwestern region of the study area, which is characterized by higher elevation and latitude, will increase by 18007.8 hm(2) (9.8% habitat suitability), while the eastern region will suffer a decrease of 9543.5 hm(2) (7.1% habitat suitability). Our results suggest that increasing areas of suitable giant panda habitat will support future giant panda expansion, and food shortage and insufficient living space will not arise as problems in the northwest Minshan Mountains, which means that giant pandas can adapt to climate change, and therefore may be resilient to climate change. Thus, for the safety and survival of giant pandas in the Baishuijiang Reserve, we propose strengthening the giant panda monitoring program in the west and improving the integrity of habitats to promote population dispersal with adjacent populations in the east. PMID- 26811743 TI - An anatomical study of arcuate foramen and its clinical implications: a case report. AB - BACKGROUND: The objective of this paper is to describe the relationship of the vertebral artery (VA) to the Atlas (C1) in the sub-occipital region in the presence of arcuate foramen; and discuss the clinical implications related to manual therapies and surgical implications related to screw placement. This study is an anatomical cadaveric case report of symmetrical bilateral lateral and dorsal arcuate foramina on the C1 dorsal arch. CASE PRESENTATION: Out of 40 cadavers that were available for use in teaching anatomy in the university setting, three presented with anomalies of the C1 dorsal arch. The sub-occipital regions were skillfully prosected to preserve related structures, especially VAs, sub-occipital and greater occipital nerves. Visual observations, photographs, measurements, and radiographic examinations were performed between January 15, 2014 and August 25, 2014. One cadaver (Specimen A) presented with complete bilateral ossified arcuate foramina, and two presented with partial ossification of the atlanto-occipital membrane. Specimen A presented the bilateral anomaly which is almost symmetrical. The VAs were found passing through double foramina (lateral and dorsal) on each side. CONCLUSIONS: Arcuate foramina have been shown to be commonly found anomalies with highly variable shapes and sizes, even in the same individual with a bilateral condition. This study found a rare type of the anomaly associated with the C1 dorsal arch, which protected the VA against manual pressure. However, VA, in this case, would be more susceptible to dissection. The presence of the arcuate foramen would also complicate screw placement during surgery. Clinical pre-screening for signs of vertebrobasilar insufficiency is important for chiropractic and manual therapies. PMID- 26811745 TI - Dominant male song performance reflects current immune state in a cooperatively breeding songbird. AB - Conspicuous displays are thought to have evolved as signals of individual "quality", though precisely what they encode remains a focus of debate. While high quality signals may be produced by high quality individuals due to "good genes" or favourable early-life conditions, whether current immune state also impacts signalling performance remains poorly understood, particularly in social species. Here, we experimentally demonstrate that male song performance is impaired by immune system activation in the cooperatively breeding white-browed sparrow weaver (Plocepasser mahali). We experimentally activated the immune system of free-living dominant males via subcutaneous injection of phytohemagglutinin (PHA) and contrasted its effects with those of a control (phosphate buffered saline) injection. PHA-challenged males showed significant reductions in both the duration and the rate of their song performance, relative to controls, and this could not be readily attributed to effects of the challenge on body mass, as no such effects were detected. Furthermore, male song performance prior to immune-challenge predicted the scale of the inflammatory response to the challenge. Our findings suggest that song performance characteristics are impacted by current immune state. This link between current state and signal performance might therefore contribute to enforcing the honesty of signal performance characteristics. Impacts of current state on signaling may be of particular importance in social species, where subordinates may benefit from an ability to identify and subsequently challenge same-sex dominants in a weakened state. PMID- 26811746 TI - A conserved pattern in plant-mediated interactions between herbivores. AB - Plant-mediated interactions between herbivores are important determinants of community structure and plant performance in natural and agricultural systems. Current research suggests that the outcome of the interactions is determined by herbivore and plant identity, which may result in stochastic patterns that impede adaptive evolution and agricultural exploitation. However, few studies have systemically investigated specificity versus general patterns in a given plant system by varying the identity of all involved players. We investigated the influence of herbivore identity and plant genotype on the interaction between leaf-chewing and root-feeding herbivores in maize using a partial factorial design. We assessed the influence of leaf induction by oral secretions of six different chewing herbivores on the response of nine different maize genotypes and three different root feeders. Contrary to our expectations, we found a highly conserved pattern across all three dimensions of specificity: The majority of leaf herbivores elicited a negative behavioral response from the different root feeders in the large majority of tested plant genotypes. No facilitation was observed in any of the treatment combinations. However, the oral secretions of one leaf feeder and the responses of two maize genotypes did not elicit a response from a root-feeding herbivore. Together, these results suggest that plant-mediated interactions in the investigated system follow a general pattern, but that a degree of specificity is nevertheless present. Our study shows that within a given plant species, plant-mediated interactions between herbivores of the same feeding guild can be stable. This stability opens up the possibility of adaptations by associated organisms and suggests that plant-mediated interactions may contribute more strongly to evolutionary dynamics in terrestrial (agro)ecosystems than previously assumed. PMID- 26811747 TI - Effects of fertilization on microbial abundance and emissions of greenhouse gases (CH4 and N2O) in rice paddy fields. AB - This study is to explore effects of nitrogen application and straw incorporation on abundance of relevant microbes and CH 4 and N2O fluxes in a midseason aerated rice paddy field. Fluxes of CH 4 and N2O were recorded, and abundance of relevant soil microbial functional genes was determined during rice-growing season in a 6 year-long fertilization experiment field in China. Results indicate that application of urea significantly changed the functional microbial composition, while the influence of straw incorporation was not significant. Application of urea significantly decreased the gene abundances of archaeal amoA and mcrA, but it significantly increased the gene abundances of bacterial amoA. CH 4 emission was significantly increased by fresh straw incorporation. Incorporation of burnt straw tended to increase CH 4 emission, while the urea application had no obvious effect on CH 4 emission. N2O emission was significantly increased by urea application, while fresh or burnt straw incorporation tended to decrease N2O emission. The functional microbial composition did not change significantly over time, although the abundances of pmoA, archaeal amoA, nirS, and nosZ genes changed significantly. The change of CH 4 emission showed an inverse trend with the one of the N2O emissions over time. To some extent, the abundance of some functional genes in this study can explain CH 4 and N2O emissions. However, the correlation between CH 4 and N2O emissions and the abundance of related functional genes was not significant. Environmental factors, such as soil Eh, may be more related to CH 4 and N2O emissions. PMID- 26811748 TI - Population genomics of divergence among extreme and intermediate color forms in a polymorphic insect. AB - Geographic variation in insect coloration is among the most intriguing examples of rapid phenotypic evolution and provides opportunities to study mechanisms of phenotypic change and diversification in closely related lineages. The bumble bee Bombus bifarius comprises two geographically disparate color groups characterized by red-banded and black-banded abdominal pigmentation, but with a range of spatially and phenotypically intermediate populations across western North America. Microsatellite analyses have revealed that B. bifarius in the USA are structured into two major groups concordant with geography and color pattern, but also suggest ongoing gene flow among regional populations. In this study, we better resolve the relationships among major color groups to better understand evolutionary mechanisms promoting and maintaining such polymorphism. We analyze >90,000 and >25,000 single-nucleotide polymorphisms derived from transcriptome (RNAseq) and double digest restriction site associated DNA sequencing (ddRAD), respectively, in representative samples from spatial and color pattern extremes in B. bifarius as well as phenotypic and geographic intermediates. Both ddRAD and RNAseq data illustrate substantial genome-wide differentiation of the red-banded (eastern) color form from both black-banded (western) and intermediate (central) phenotypes and negligible differentiation among the latter populations, with no obvious admixture among bees from the two major lineages. Results thus indicate much stronger background differentiation among B. bifarius lineages than expected, highlighting potential challenges for revealing loci underlying color polymorphism from population genetic data alone. These findings will have significance for resolving taxonomic confusion in this species and in future efforts to investigate color-pattern evolution in B. bifarius and other polymorphic bumble bee species. PMID- 26811749 TI - Molecular and iridescent feather reflectance data reveal recent genetic diversification and phenotypic differentiation in a cloud forest hummingbird. AB - The present day distribution and spatial genetic diversity of Mesoamerican biota reflects a long history of responses to habitat change. The hummingbird Lampornis amethystinus is distributed in northern Mesoamerica, with geographically disjunct populations. Based on sampling across the species range using mitochondrial DNA (mtDNA) sequences and nuclear microsatellites jointly analysed with phenotypic and climatic data, we (1) test whether the fragmented distribution is correlated with main evolutionary lineages, (2) assess body size and plumage color differentiation of populations in geographic isolation, and (3) evaluate a set of divergence scenarios and demographic patterns of the hummingbird populations. Analysis of genetic variation revealed four main groups: blue-throated populations (Sierra Madre del Sur); two groups of amethyst-throated populations (Trans-Mexican Volcanic Belt and Sierra Madre Oriental); and populations east of the Isthmus of Tehuantepec (IT) with males showing an amethyst throat. The most basal split is estimated to have originated in the Pleistocene, 2.39-0.57 million years ago (MYA), and corresponded to groups of populations separated by the IT. However, the estimated recent divergence time between blue- and amethyst-throated populations does not correspond to the 2-MY needed to be in isolation for substantial plumage divergence, likely because structurally iridescent colors are more malleable than others. Results of species distribution modeling and Approximate Bayesian Computation analysis fit a model of lineage divergence west of the Isthmus after the Last Glacial Maximum (LGM), and that the species' suitable habitat was disjunct during past and current conditions. These results challenge the generality of the contraction/expansion glacial model to cloud forest-interior species and urges management of cloud forest, a highly vulnerable ecosystem to climate change and currently facing destruction, to prevent further loss of genetic diversity or extinction. PMID- 26811750 TI - Oxidative stress and life histories: unresolved issues and current needs. AB - Life-history theory concerns the trade-offs that mold the patterns of investment by animals between reproduction, growth, and survival. It is widely recognized that physiology plays a role in the mediation of life-history trade-offs, but the details remain obscure. As life-history theory concerns aspects of investment in the soma that influence survival, understanding the physiological basis of life histories is related, but not identical, to understanding the process of aging. One idea from the field of aging that has gained considerable traction in the area of life histories is that life-history trade-offs may be mediated by free radical production and oxidative stress. We outline here developments in this field and summarize a number of important unresolved issues that may guide future research efforts. The issues are as follows. First, different tissues and macromolecular targets of oxidative stress respond differently during reproduction. The functional significance of these changes, however, remains uncertain. Consequently there is a need for studies that link oxidative stress measurements to functional outcomes, such as survival. Second, measurements of oxidative stress are often highly invasive or terminal. Terminal studies of oxidative stress in wild animals, where detailed life-history information is available, cannot generally be performed without compromising the aims of the studies that generated the life-history data. There is a need therefore for novel non-invasive measurements of multi-tissue oxidative stress. Third, laboratory studies provide unrivaled opportunities for experimental manipulation but may fail to expose the physiology underpinning life-history effects, because of the benign laboratory environment. Fourth, the idea that oxidative stress might underlie life-history trade-offs does not make specific enough predictions that are amenable to testing. Moreover, there is a paucity of good alternative theoretical models on which contrasting predictions might be based. Fifth, there is an enormous diversity of life-history variation to test the idea that oxidative stress may be a key mediator. So far we have only scratched the surface. Broadening the scope may reveal new strategies linked to the processes of oxidative damage and repair. Finally, understanding the trade-offs in life histories and understanding the process of aging are related but not identical questions. Scientists inhabiting these two spheres of activity seldom collide, yet they have much to learn from each other. PMID- 26811752 TI - Phylogenetic ecology of gall crabs (Cryptochiridae) as associates of mushroom corals (Fungiidae). AB - Coral-associated fauna is a relatively understudied topic. Hence, the nature of the relationship between an associated organism and its host is usually unknown. In the present study, the obligate associations between gall crabs (Decapoda: Cryptochiridae) and mushroom corals (Scleractinia: Fungiidae) are reviewed from a phylogenetic perspective. Based on field surveys, examination of museum material and a literature review, a total of 35 fungiid species have been found that act as hosts for four gall crab species. Fungiid-associated gall crabs appear to be more geographically widespread than previously known, with new records showing their occurrences from the Red Sea and western Indian Ocean all the way to the central Pacific Ocean. The obligate nature of the association between cryptochirids and their hosts makes them an ideal model taxon to test for possible cospeciation events. The congruence between their phylogenies was tested by using the program Jane 4.0, resulting in cospeciation and duplication events between the crabs and their host corals. The sharing of several closely related host coral species by the same gall crab species or genus may provide support to models indicating phylogenetic relationships within the Scleractinia. PMID- 26811751 TI - Genetic variation, multiple paternity, and measures of reproductive success in the critically endangered hawksbill turtle (Eretmochelys imbricata). AB - The Yucatan Peninsula in Mexico contains some of the largest breeding groups of the globally distributed and critically endangered hawksbill turtle (Eretmochelys imbricata). An improved understanding of the breeding system of this species and how its genetic variation is structured among nesting areas is required before the threats to its survival can be properly evaluated. Here, we genotype 1195 hatchlings and 41 nesting females at 12 microsatellite loci to assess levels of multiple paternity, genetic variation and whether individual levels of homozygosity are associated with reproductive success. Of the 50 clutches analyzed, only 6% have multiple paternity. The distribution of pairwise relatedness among nesting localities (rookeries) was not random with elevated within-rookery relatedness, and declining relatedness with geographic distance indicating some natal philopatry. Although there was no strong evidence that particular rookeries had lost allelic variation via drift, younger turtles had significantly lower levels of genetic variation than older turtles, suggesting some loss of genetic variation. At present there is no indication that levels of genetic variation are associated with measures of reproductive success such as clutch size, hatching success, and frequency of infertile eggs. PMID- 26811754 TI - Matrix quality and disturbance frequency drive evolution of species behavior at habitat boundaries. AB - Previous theoretical studies suggest that a species' landscape should influence the evolution of its dispersal characteristics, because landscape structure affects the costs and benefits of dispersal. However, these studies have not considered the evolution of boundary crossing, that is, the tendency of animals to cross from habitat to nonhabitat ("matrix"). It is important to understand this dispersal behavior, because of its effects on the probability of population persistence. Boundary-crossing behavior drives the rate of interaction with matrix, and thus, it influences the rate of movement among populations and the risk of dispersal mortality. We used an individual-based, spatially explicit model to simulate the evolution of boundary crossing in response to landscape structure. Our simulations predict higher evolved probabilities of boundary crossing in landscapes with more habitat, less fragmented habitat, higher-quality matrix, and more frequent disturbances (i.e., fewer generations between local population extinction events). Unexpectedly, our simulations also suggest that matrix quality and disturbance frequency have much stronger effects on the evolution of boundary crossing than either habitat amount or habitat fragmentation. Our results suggest that boundary-crossing responses are most affected by the costs of dispersal through matrix and the benefits of escaping local extinction events. Evolution of optimal behavior at habitat boundaries in response to the landscape may have implications for species in human-altered landscapes, because this behavior may become suboptimal if the landscape changes faster than the species' evolutionary response to that change. Understanding how matrix quality and habitat disturbance drive evolution of behavior at boundaries, and how this in turn influences the extinction risk of species in human-altered landscapes should help us identify species of conservation concern and target them for management. PMID- 26811753 TI - Combining the least cost path method with population genetic data and species distribution models to identify landscape connectivity during the late Quaternary in Himalayan hemlock. AB - Himalayan hemlock (Tsuga dumosa) experienced a recolonization event during the Quaternary period; however, the specific dispersal routes are remain unknown. Recently, the least cost path (LCP) calculation coupled with population genetic data and species distribution models has been applied to reveal the landscape connectivity. In this study, we utilized the categorical LCP method, combining species distribution of three periods (the last interglacial, the last glacial maximum, and the current period) and locality with shared chloroplast, mitochondrial, and nuclear haplotypes, to identify the possible dispersal routes of T. dumosa in the late Quaternary. Then, both a coalescent estimate of migration rates among regional groups and establishment of genetic divergence pattern were conducted. After those analyses, we found that the species generally migrated along the southern slope of Himalaya across time periods and genomic makers, and higher degree of dispersal was in the present and mtDNA haplotype. Furthermore, the direction of range shifts and strong level of gene flow also imply the existence of Himalayan dispersal path, and low area of genetic divergence pattern suggests that there are not any obvious barriers against the dispersal pathway. Above all, we inferred that a dispersal route along the Himalaya Mountains could exist, which is an important supplement for the evolutionary history of T. dumosa. Finally, we believed that this integrative genetic and geospatial method would bring new implications for the evolutionary process and conservation priority of species in the Tibetan Plateau. PMID- 26811755 TI - Species mtDNA genetic diversity explained by infrapopulation size in a host symbiont system. AB - Understanding what shapes variation in genetic diversity among species remains a major challenge in evolutionary ecology, and it has been seldom studied in parasites and other host-symbiont systems. Here, we studied mtDNA variation in a host-symbiont non-model system: 418 individual feather mites from 17 feather mite species living on 17 different passerine bird species. We explored how a surrogate of census size, the median infrapopulation size (i.e., the median number of individual parasites per infected host individual), explains mtDNA genetic diversity. Feather mite species genetic diversity was positively correlated with mean infrapopulation size, explaining 34% of the variation. As expected from the biology of feather mites, we found bottleneck signatures for most of the species studied but, in particular, three species presented extremely low mtDNA diversity values given their infrapopulation size. Their star-like haplotype networks (in contrast with more reticulated networks for the other species) suggested that their low genetic diversity was the consequence of severe bottlenecks or selective sweeps. Our study shows for the first time that mtDNA diversity can be explained by infrapopulation sizes, and suggests that departures from this relationship could be informative of underlying ecological and evolutionary processes. PMID- 26811756 TI - Modeling behavioral thermoregulation in a climate change sentinel. AB - When possible, many species will shift in elevation or latitude in response to rising temperatures. However, before such shifts occur, individuals will first tolerate environmental change and then modify their behavior to maintain heat balance. Behavioral thermoregulation allows animals a range of climatic tolerances and makes predicting geographic responses under future warming scenarios challenging. Because behavioral modification may reduce an individual's fecundity by, for example, limiting foraging time and thus caloric intake, we must consider the range of behavioral options available for thermoregulation to accurately predict climate change impacts on individual species. To date, few studies have identified mechanistic links between an organism's daily activities and the need to thermoregulate. We used a biophysical model, Niche Mapper, to mechanistically model microclimate conditions and thermoregulatory behavior for a temperature-sensitive mammal, the American pika (Ochotona princeps). Niche Mapper accurately simulated microclimate conditions, as well as empirical metabolic chamber data for a range of fur properties, animal sizes, and environmental parameters. Niche Mapper predicted pikas would be behaviorally constrained because of the need to thermoregulate during the hottest times of the day. We also showed that pikas at low elevations could receive energetic benefits by being smaller in size and maintaining summer pelage during longer stretches of the active season under a future warming scenario. We observed pika behavior for 288 h in Glacier National Park, Montana, and thermally characterized their rocky, montane environment. We found that pikas were most active when temperatures were cooler, and at sites characterized by high elevations and north-facing slopes. Pikas became significantly less active across a suite of behaviors in the field when temperatures surpassed 20 degrees C, which supported a metabolic threshold predicted by Niche Mapper. In general, mechanistic predictions and empirical observations were congruent. This research is unique in providing both an empirical and mechanistic description of the effects of temperature on a mammalian sentinel of climate change, the American pika. Our results suggest that previously underinvestigated characteristics, specifically fur properties and body size, may play critical roles in pika populations' response to climate change. We also demonstrate the potential importance of considering behavioral thermoregulation and microclimate variability when predicting animal responses to climate change. PMID- 26811757 TI - Rapid and repeatable shifts in life-history timing of Rhagoletis pomonella (Diptera: Tephritidae) following colonization of novel host plants in the Pacific Northwestern United States. AB - Host shifts of phytophagous insect specialists to novel plants can result in divergent ecological adaptation, generating reproductive isolation and potentially new species. Rhagoletis pomonella fruit flies in eastern North America underwent a host shift ~160 ya from native downy hawthorn (Crataegus mollis) to introduced, domesticated apple (Malus domestica). Divergent selection on diapause phenology related to the earlier fruiting time of apples versus downy hawthorns resulted in partial allochronic reproductive isolation between the fly races. Here, we test for how rapid and repeatable shifts in life-history timing are driving ecological divergence of R. pomonella in the Pacific Northwestern USA. The fly was introduced into the region via larval-infested apples 40-65 ya and now attacks native black hawthorn (Crataegus douglasii) and introduced ornamental hawthorn (Crataegus monogyna), in addition to early- and late-maturing apple varieties in the region. To investigate the life-history timing hypothesis, we used a field-based experiment to characterize the host-associated eclosion and flight activity patterns of adults, and the feeding times of larvae at a field site in Vancouver, Washington. We also assessed the degree to which differences in host-fruiting time generate allochronic isolation among apple-, black hawthorn , and ornamental hawthorn-associated fly populations. We conclude that host associated fly populations are temporally offset 24.4% to 92.6% in their seasonal distributions. Our results imply that R. pomonella possesses the capacity for rapid and repeatable shifts in diapause life history to match host-fruiting phenology, which can generate ecologically based reproductive isolation, and potentially biodiversity in the process. PMID- 26811758 TI - Reproductive isolation is mediated by pollen incompatibility in sympatric populations of two Arnebia species. AB - To explore uncertain aspects of the processes that maintain species boundaries, we evaluated contributions of pre- and postpollination reproductive isolation mechanisms in sympatric populations of Arnebia guttata and A. szechenyi. For this, we investigated their phylogenetic relationships, traits, microenvironments, pollinator visits, action of natural selection on floral traits, and the outcome of hand pollination between the two species. Phylogenetic analysis indicates that A. szechenyi is a derived species that could be closely related to A. guttata, and both could be diploid species. Arnebia guttata flowers have larger parts than A. szechenyi flowers, but smaller nectar guides. Soil supporting A. szechenyi had higher water contents than soil supporting neighboring populations of A. guttata (in accordance with their geographical distributions). The pollinators shared by the two species preferred A. szechenyi flowers, but interspecific visitations were frequent. We found evidence of conflicting selection pressures on floral tube length, flower diameter and nectar guide size mediated via male fitness, and on flower diameter and floral tube diameter via female fitness. Hand-pollination experiments indicate complete pollen incompatibility between the two species. Our results suggest that postpollination prezygotic mechanisms are largely responsible for reproductive isolation of sympatric populations of the two Arnebia species. PMID- 26811759 TI - No personality without experience? A test on Rana dalmatina tadpoles. AB - While the number of studies reporting the presence of individual behavioral consistency (animal personality, behavioral syndrome) has boomed in the recent years, there is still much controversy about the proximate and ultimate mechanisms resulting in the phenomenon. For instance, direct environmental effects during ontogeny (phenotypic plasticity) as the proximate mechanism behind the emergence of consistent individual differences in behavior are usually overlooked compared to environmental effects operating across generations (genetic adaptation). Here, we tested the effects of sociality and perceived predation risk during ontogeny on the strength of behavioral consistency in agile frog (Rana dalmatina) tadpoles in a factorial common garden experiment. Tadpoles reared alone and without predatory cues showed zero repeatability within (i.e., lack of personality) and zero correlation between (i.e., lack of syndrome) activity and risk-taking. On the other hand, cues from predators alone induced both activity and risk-taking personalities, while cues from predators and conspecifics together resulted in an activity - risk-taking behavioral syndrome. Our results show that individual experience has an unequivocal role in the emergence of behavioral consistency. In this particular case, the development of behavioral consistency was most likely the result of genotype * environment interactions, or with other words, individual variation in behavioral plasticity. PMID- 26811760 TI - Quality and quantity: transitions in antimicrobial gland use for parasite defense. AB - Parasites are a major force in evolution, and understanding how host life history affects parasite pressure and investment in disease resistance is a general problem in evolutionary biology. The threat of disease may be especially strong in social animals, and ants have evolved the unique metapleural gland (MG), which in many taxa produce antimicrobial compounds that have been argued to have been a key to their ecological success. However, the importance of the MG in the disease resistance of individual ants across ant taxa has not been examined directly. We investigate experimentally the importance of the MG for disease resistance in the fungus-growing ants, a group in which there is interspecific variation in MG size and which has distinct transitions in life history. We find that more derived taxa rely more on the MG for disease resistance than more basal taxa and that there are a series of evolutionary transitions in the quality, quantity, and usage of the MG secretions, which correlate with transitions in life history. These shifts show how even small clades can exhibit substantial transitions in disease resistance investment, demonstrating that host-parasite relationships can be very dynamic and that targeted experimental, as well as large-scale, comparative studies can be valuable for identifying evolutionary transitions. PMID- 26811761 TI - A simulation study of sample size for DNA barcoding. AB - For some groups of organisms, DNA barcoding can provide a useful tool in taxonomy, evolutionary biology, and biodiversity assessment. However, the efficacy of DNA barcoding depends on the degree of sampling per species, because a large enough sample size is needed to provide a reliable estimate of genetic polymorphism and for delimiting species. We used a simulation approach to examine the effects of sample size on four estimators of genetic polymorphism related to DNA barcoding: mismatch distribution, nucleotide diversity, the number of haplotypes, and maximum pairwise distance. Our results showed that mismatch distributions derived from subsamples of >=20 individuals usually bore a close resemblance to that of the full dataset. Estimates of nucleotide diversity from subsamples of >=20 individuals tended to be bell-shaped around that of the full dataset, whereas estimates from smaller subsamples were not. As expected, greater sampling generally led to an increase in the number of haplotypes. We also found that subsamples of >=20 individuals allowed a good estimate of the maximum pairwise distance of the full dataset, while smaller ones were associated with a high probability of underestimation. Overall, our study confirms the expectation that larger samples are beneficial for the efficacy of DNA barcoding and suggests that a minimum sample size of 20 individuals is needed in practice for each population. PMID- 26811762 TI - Genetic differentiation of the regional Plutella xylostella populations across the Taiwan Strait based on identification of microsatellite markers. AB - Movement of individuals through events, such as storms or crop transportation, may affect survival and distribution of insect pests, as well as population genetic structure at a regional scale. Understanding what factors contribute to gene flow in pest populations remains very important for sustainable pest management. The diamondback moth (Plutella xylostella) is an insect pest well known for its capacity of moving over short to long distances. Here, we used newly isolated microsatellite markers to analyze the genetic structure of nine populations across the Taiwan Strait of China (Taiwan and Fujian). A total of 12,152 simple sequence repeats (SSRs) were initially identified from the P. xylostella transcriptome (~94 Mb), with an average of 129 SSRs per Mb. Nine SSRs were validated to be polymorphic markers, and eight were used for this population genetic study. Our results showed that the P. xylostella populations could be divided into distinct two clusters, which is likely due to the year-round airflows in this region. A pattern of isolation by distance among the local populations within Fujian was found, and may be related to vegetable transportation. Considering the complexity of the P. xylostella population genetic structure from local and regional to global levels, we propose that developing ecologically sound strategies for managing this pest will require knowledge of the link between behavioral and population ecology and its genetic structure. PMID- 26811763 TI - Climate and density influence annual survival and movement in a migratory songbird. AB - Assessing the drivers of survival across the annual cycle is important for understanding when and how population limitation occurs in migratory animals. Density-dependent population regulation can occur during breeding and nonbreeding periods, and large-scale climate cycles can also affect survival throughout the annual cycle via their effects on local weather and vegetation productivity. Most studies of survival use mark-recapture techniques to estimate apparent survival, but true survival rates remain obscured due to unknown rates of permanent emigration. This is especially problematic when assessing annual survival of migratory birds, whose movement between breeding attempts, or breeding dispersal, can be substantial. We used a multistate approach to examine drivers of annual survival and one component of breeding dispersal (habitat-specific movements) in a population of American redstarts (Setophaga ruticilla) over 11 years in two adjacent habitat types. Annual survival displayed a curvilinear relation to the Southern Oscillation Index, with lower survival during La Nina and El Nino conditions. Although redstart density had no impact on survival, habitat-specific density influenced local movements between habitat types, with redstarts being less likely to disperse from their previous year's breeding habitat as density within that habitat increased. This finding was strongest in males and may be explained by conspecific attraction influencing settlement decisions. Survival was lowest in young males, but movement was highest in this group, indicating that apparent survival rates were likely biased low due to permanent emigration. Our findings demonstrate the utility of examining breeding dispersal in mark recapture studies and complement recent work using spatially explicit models of dispersal probability to obtain greater accuracy in survival estimates. PMID- 26811764 TI - Thermal tolerance and climate warming sensitivity in tropical snails. AB - Tropical ectotherms are predicted to be especially vulnerable to climate change because their thermal tolerance limits generally lie close to current maximum air temperatures. This prediction derives primarily from studies on insects and lizards and remains untested for other taxa with contrasting ecologies. We studied the HCT (heat coma temperatures) and ULT (upper lethal temperatures) of 40 species of tropical eulittoral snails (Littorinidae and Neritidae) inhabiting exposed rocky shores and shaded mangrove forests in Oceania, Africa, Asia and North America. We also estimated extremes in animal body temperature at each site using a simple heat budget model and historical (20 years) air temperature and solar radiation data. Phylogenetic analyses suggest that HCT and ULT exhibit limited adaptive variation across habitats (mangroves vs. rocky shores) or geographic locations despite their contrasting thermal regimes. Instead, the elevated heat tolerance of these species (HCT = 44.5 +/- 1.8 degrees C and ULT = 52.1 +/- 2.2 degrees C) seems to reflect the extreme temperature variability of intertidal systems. Sensitivity to climate warming, which was quantified as the difference between HCT or ULT and maximum body temperature, differed greatly between snails from sunny (rocky shore; Thermal Safety Margin, TSM = -14.8 +/- 3.3 degrees C and -6.2 +/- 4.4 degrees C for HCT and ULT, respectively) and shaded (mangrove) habitats (TSM = 5.1 +/- 3.6 degrees C and 12.5 +/- 3.6 degrees C). Negative TSMs in rocky shore animals suggest that mortality is likely ameliorated during extreme climatic events by behavioral thermoregulation. Given the low variability in heat tolerance across species, habitat and geographic location account for most of the variation in TSM and may adequately predict the vulnerability to climate change. These findings caution against generalizations on the impact of global warming across ectothermic taxa and highlight how the consideration of nonmodel animals, ecological transitions, and behavioral responses may alter predictions of studies that ignore these biological details. PMID- 26811765 TI - Modeling and predicting the growth of the mussel, Mytilus edulis: implications for planning of aquaculture and eutrophication mitigation. AB - The increased pressure on the marine ecosystems highlights the need for policies and integrated approaches for sustainable management of coastal areas. Spatial planning based on geographic information of human activities, ecological structures and functions, and their associated goods and services is a fundamental component in this context. Here, we evaluate the potential of predictive modeling to provide spatial data on one ecosystem function, mussel growth for use in such processes. We developed a methodology based on statistical modeling, spatial prediction, and mapping for the relative growth of the blue mussel, Mytilus edulis. We evaluated the performance of different modeling techniques and classification schemes using empirical measurements of growth from 144 sampling sites and data on biological, chemical, and physical predictors. Following comparisons of the different techniques and schemes, we developed random forest models to predict growth along the Swedish west coast. Implemented into GIS the best model produced in this study predicts that low, intermediate, and high growth rates can be expected in 53%, 32%, and 15% of modeled area, respectively. The results of this study also suggest that the nature and quality of predictor data hold the key to improving the predictive power of models. On a more general note, this study exemplifies a feasible approach based on measuring, modeling, and mapping for obtaining scientifically based spatial information on ecosystem functions and services affected by a complex set of factors. Such information is fundamental for maritime spatial planning and ecosystem-based management and its importance is likely to increase in the future. Because of its close link to nutrient assimilation and production yield, site-specific information of soft tissue growth such as the map of predicted growth rate developed in this study can be used as a tool for optimizing actions aimed at mitigating eutrophication and aquaculture operations and in maritime spatial planning processes of coastal areas. PMID- 26811767 TI - Interspecific interactions between wild felids vary across scales and levels of urbanization. AB - Ongoing global landscape change resulting from urbanization is increasingly linked to changes in species distributions and community interactions. However, relatively little is known about how urbanization influences competitive interactions among mammalian carnivores, particularly related to wild felids. We evaluated interspecific interactions between medium- and large-sized carnivores across a gradient of urbanization and multiple scales. Specifically, we investigated spatial and temporal interactions of bobcats and pumas by evaluating circadian activity patterns, broad-scale seasonal interactions, and fine-scale daily interactions in wildland-urban interface (WUI), exurban residential development, and wildland habitats. Across levels of urbanization, interspecific interactions were evaluated using two-species and single-species occupancy models with data from motion-activated cameras. As predicted, urbanization increased the opportunity for interspecific interactions between wild felids. Although pumas did not exclude bobcats from areas at broad spatial or temporal scales, bobcats responded behaviorally to the presence of pumas at finer scales, but patterns varied across levels of urbanization. In wildland habitat, bobcats avoided using areas for short temporal periods after a puma visited an area. In contrast, bobcats did not appear to avoid areas that pumas recently visited in landscapes influenced by urbanization (exurban development and WUI habitat). In addition, overlap in circadian activity patterns between bobcats and pumas increased in exurban development compared to wildland habitat. Across study areas, bobcats used sites less frequently as the number of puma photographs increased at a site. Overall, bobcats appear to shape their behavior at fine spatial and temporal scales to reduce encounters with pumas, but residential development can potentially alter these strategies and increase interaction opportunities. We explore three hypotheses to explain our results of how urbanization affected interspecific interactions that consider activity patterns, landscape configuration, and animal scent marking. Altered competitive interactions between animals in urbanized landscapes could potentially increase aggressive encounters and the frequency of disease transmission. PMID- 26811766 TI - Competitive outcome of multiple infections in a behavior-manipulating virus/wasp interaction. AB - Infections by multiple parasites are common in nature and may impact the evolution of host-parasite interactions. We investigated the existence of multiple infections involving the DNA virus LbFV and the Drosophila parasitoid Leptopilina boulardi. This vertically transmitted virus forces infected females to lay their eggs in already parasitized Drosophila larvae (a behavior called superparasitism), thus favoring its spread through horizontal transmission. Previous theoretical work indicated that the evolution of the level of the manipulation strongly depends on whether infected parasitoids can be re-infected or not. Here, we describe a strain of LbFV that differs from the reference strain by showing a deletion within the locus used for PCR detection. We used this polymorphism to test for the existence of multiple infections in this system. Viral strains did not differ on their vertical or horizontal transmission rates nor on the way they affect the parasitoid's phenotype, including their ability to manipulate behavior. Although already infected parasitoids were much less susceptible to new infection than uninfected ones, frequent coinfection was detected. However, following coinfection, competition between viral strains led to the rapid elimination of one strain or the other after a few generations of vertical transmission. We discuss the implications of these results for the evolution of the behavioral manipulation. PMID- 26811768 TI - When can stress facilitate divergence by altering time to flowering? AB - Stressors and heterogeneity are ubiquitous features of natural environments, and theory suggests that when environmental qualities alter flowering schedules through phenotypic plasticity, assortative mating can result that promotes evolutionary divergence. Therefore, it is important to determine whether common ecological stressors induce similar changes in flowering time. We review previous studies to determine whether two important stressors, water restriction and herbivory, induce consistent flowering time responses among species; for example, how often do water restriction and herbivory both delay flowering? We focus on the direction of change in flowering time, which affects the potential for divergence in heterogeneous environments. We also tested whether these stressors influenced time to flowering and nonphenology traits using Mimulus guttatus. The literature review suggests that water restriction has variable effects on flowering time, whereas herbivory delays flowering with exceptional consistency. In the Mimulus experiment, low water and herbivory advanced and delayed flowering, respectively. Overall, our results temper theoretical predictions for evolutionary divergence due to habitat-induced changes in flowering time; in particular, we discuss how accounting for variation in the direction of change in flowering time can either increase or decrease the potential for divergence. In addition, we caution against adaptive interpretations of stress-induced phenology shifts. PMID- 26811769 TI - Patterns of contact call differentiation in the panmictic East African Abyssinian White-eye Zosterops abyssinicus (Aves: Passeriformes). AB - Species distribution patterns range from highly disjunct to continuous, depending on their ecological demands and the availability of respective habitats. East African savannahs are mostly interconnected and ecologically comparatively homogenous and thus provide a prerequisite for a rather panmictic distribution pattern for species occurring in this habitat. The Abyssinian white-eye Zosterops abyssinicus is a savannah inhabiting bird species, representing such a continuous distribution. This species occurs in high abundances and is very mobile, and past population genetic studies have suggested that gene flow is high and genetic differentiation is low even across relatively large geographic distances. Further, only little morphological differences were found. In order to test for potential divergence in acoustic traits despite its interconnected geographic distribution, we analyzed 2795 contact calls of Z. abyssinicus, which were recorded at 19 sites across Kenya. Our data indicate weak, but significant differentiation in call characteristics across latitudinal gradients. We found strong changes in call characteristics in populations where Z. abyssinicus occurs in sympatry with its highland congener, Zosterops poliogaster. However, the changes in call characteristics in sympatry were in different directions and lead to strong differentiation of the sympatric populations to other conspecific populations potentially representing a case of cascade reinforcement. The detected spatial gradients likely result from ecological differences and balancing effects of natural and sexual selection. PMID- 26811770 TI - European wildcat populations are subdivided into five main biogeographic groups: consequences of Pleistocene climate changes or recent anthropogenic fragmentation? AB - Extant populations of the European wildcat are fragmented across the continent, the likely consequence of recent extirpations due to habitat loss and over hunting. However, their underlying phylogeographic history has never been reconstructed. For testing the hypothesis that the European wildcat survived the Ice Age fragmented in Mediterranean refuges, we assayed the genetic variation at 31 microsatellites in 668 presumptive European wildcats sampled in 15 European countries. Moreover, to evaluate the extent of subspecies/population divergence and identify eventual wild * domestic cat hybrids, we genotyped 26 African wildcats from Sardinia and North Africa and 294 random-bred domestic cats. Results of multivariate analyses and Bayesian clustering confirmed that the European wild and the domestic cats (plus the African wildcats) belong to two well-differentiated clusters (average F ST = 0.159, r st = 0.392, P > 0.001; Analysis of molecular variance [AMOVA]). We identified from c. 5% to 10% cryptic hybrids in southern and central European populations. In contrast, wild-living cats in Hungary and Scotland showed deep signatures of genetic admixture and introgression with domestic cats. The European wildcats are subdivided into five main genetic clusters (average F ST = 0.103, r st = 0.143, P > 0.001; AMOVA) corresponding to five biogeographic groups, respectively, distributed in the Iberian Peninsula, central Europe, central Germany, Italian Peninsula and the island of Sicily, and in north-eastern Italy and northern Balkan regions (Dinaric Alps). Approximate Bayesian Computation simulations supported late Pleistocene early Holocene population splittings (from c. 60 k to 10 k years ago), contemporary to the last Ice Age climatic changes. These results provide evidences for wildcat Mediterranean refuges in southwestern Europe, but the evolution history of eastern wildcat populations remains to be clarified. Historical genetic subdivisions suggest conservation strategies aimed at enhancing gene flow through the restoration of ecological corridors within each biogeographic units. Concomitantly, the risk of hybridization with free-ranging domestic cats along corridor edges should be carefully monitored. PMID- 26811771 TI - A trait-based framework for stream algal communities. AB - The use of trait-based approaches to detect effects of land use and climate change on terrestrial plant and aquatic phytoplankton communities is increasing, but such a framework is still needed for benthic stream algae. Here we present a conceptual framework of morphological, physiological, behavioural and life history traits relating to resource acquisition and resistance to disturbance. We tested this approach by assessing the relationships between multiple anthropogenic stressors and algal traits at 43 stream sites. Our "natural experiment" was conducted along gradients of agricultural land-use intensity (0 95% of the catchment in high-producing pasture) and hydrological alteration (0 92% streamflow reduction resulting from water abstraction for irrigation) as well as related physicochemical variables (total nitrogen concentration and deposited fine sediment). Strategic choice of study sites meant that agricultural intensity and hydrological alteration were uncorrelated. We studied the relationships of seven traits (with 23 trait categories) to our environmental predictor variables using general linear models and an information-theoretic model-selection approach. Life form, nitrogen fixation and spore formation were key traits that showed the strongest relationships with environmental stressors. Overall, FI (farming intensity) exerted stronger effects on algal communities than hydrological alteration. The large-bodied, non-attached, filamentous algae that dominated under high farming intensities have limited dispersal abilities but may cope with unfavourable conditions through the formation of spores. Antagonistic interactions between FI and flow reduction were observed for some trait variables, whereas no interactions occurred for nitrogen concentration and fine sediment. Our conceptual framework was well supported by tests of ten specific hypotheses predicting effects of resource supply and disturbance on algal traits. Our study also shows that investigating a fairly comprehensive set of traits can help shed light on the drivers of algal community composition in situations where multiple stressors are operating. Further, to understand non-linear and non additive effects of such drivers, communities need to be studied along multiple gradients of natural variation or anthropogenic stressors. PMID- 26811772 TI - Same school, different conduct: rates of multiple paternity vary within a mixed species breeding school of semi-pelagic cichlid fish (Cyprichromis spp.). AB - Mating system variability is known to exist between and within species, often due to environmental influences. An open question is whether, vice versa, similar environmental conditions entail congruent mating behavior, for example in terms of multiple paternity, in species or populations sharing largely comparable breeding modes. This study employed microsatellite markers to investigate the incidence of multiple paternity in Cyprichromis coloratus and Cyprichromis leptosoma, two sympatric, closely related, mouthbrooding Lake Tanganyika cichlids with similar ecological and behavioral characteristics including the formation of open-water schools. Mouthbrooding females of both species were collected from the same mixed-species breeding school at the same time, minimizing environmental variation during courtship and mating. In C. coloratus, four of 12 broods had more than one sire, with a mean of 1.33 reconstructed sires per brood. C. leptosoma exhibited multiple paternity in 18 of 22 broods, with a mean of 2.59 or 2.86 reconstructed sires per brood according to the programs gerud and colony, respectively. In addition, two broods were found to contain offspring transplanted from another brood. There was no significant difference in brood size between species, but mean sire number did differ significantly. Hence, substantial similarity in reproductive behavior along with shared environmental conditions during courtship and spawning did not lead to equal rates of polyandry or sneaking in the two species. PMID- 26811773 TI - Postdispersal nepotism in male long-tailed macaques (Macaca fascicularis). AB - Cooperative behaviors are promoted by kin selection if the costs to the actor are smaller than the fitness benefits to the recipient, weighted by the coefficient of relatedness. In primates, cooperation occurs primarily among female dyads. Due to male dispersal before sexual maturity in many primate species, however, it is unknown whether there are sufficient opportunities for selective tolerance and occasional coalitionary support for kin selection to favor male nepotistic support. We studied the effect of the presence of male kin on correlates of male reproductive success (residence time, duration of high dominance rank) in non natal male long-tailed macaques (Macaca fascicularis). We found that "related" (i.e., related at the half-sibling level or higher) males in a group have a significantly higher probability to remain in the non-natal group compared to males without relatives. Moreover, males stayed longer in a group when a relative was present at group entry or joined the same group within 3 months upon arrival. Males with co-residing relatives also maintained a high rank for longer than those without. To our knowledge, this is the first demonstration of a potential nepotistic effect on residence and rank maintenance among non-natal males in a social system without long-term alliances. PMID- 26811774 TI - Fecal antibody levels as a noninvasive method for measuring immunity to gastrointestinal nematodes in ecological studies. AB - Among-individual variation in antibody-associated immunity to gastrointestinal nematode parasites (GIN) is known be associated with life-history traits and vital rates in wild vertebrate systems. To date, measurement of levels of antibodies against GIN antigens in natural populations has exclusively been based on invasive blood sampling techniques. Previous work in laboratory rodents and ruminant livestock suggests that antibody measures from feces may provide a viable noninvasive approach. We measured total and anti-GIN antibodies of different isotypes (immunoglobulin (Ig) G, IgA and IgE) from paired samples of plasma and feces from free-living Soay sheep of different ages and sexes. We tested the correlations among these measures as well as their associations with body mass and Strongyle nematode fecal egg counts (FEC). Significant positive correlations were present among plasma and fecal anti-GIN antibody levels for IgG and IgA. Generally, correlations between total antibody levels in plasma and feces were weaker and not significant. No significant relationships were found between any antibody measures and body mass; however, fecal anti-GIN antibody levels were significantly negatively correlated with FEC. Our data clearly demonstrate the feasibility of measuring anti-GIN antibodies from fecal samples collected in natural populations. Although associations of fecal antibody levels with their plasma counterparts and FEC were relatively weak, the presence of significant correlations in the predicted direction in a relatively small and heterogeneous sample suggests fecal antibody measures could be a useful, noninvasive addition to current eco-immunological studies. PMID- 26811775 TI - Longer wings for faster springs - wing length relates to spring phenology in a long-distance migrant across its range. AB - In migratory birds, morphological adaptations for efficient migratory flight often oppose morphological adaptations for efficient behavior during resident periods. This includes adaptations in wing shape for either flying long distances or foraging in the vegetation and in climate-driven variation of body size. In addition, the timing of migratory flights and particularly the timely arrival at local breeding sites is crucial because fitness prospects depend on site-specific phenology. Thus, adaptations for efficient long-distance flights might be also related to conditions at destination areas. For an obligatory long-distance migrant, the common nightingale, we verified that wing length as the aerodynamically important trait, but not structural body size increased from the western to the eastern parts of the species range. In contrast with expectation from aerodynamic theory, however, wing length did not increase with increasing migration distances. Instead, wing length was associated with the phenology at breeding destinations, namely the speed of local spring green-up. We argue that longer wings are beneficial for adjusting migration speed to local conditions for birds breeding in habitats with fast spring green-up and thus short optimal arrival periods. We suggest that the speed of spring green-up at breeding sites is a fundamental variable determining the timing of migration that fine tune phenotypes in migrants across their range. PMID- 26811776 TI - Population genetics of the olive-winged bulbul (Pycnonotus plumosus) in a tropical urban-fragmented landscape. AB - With increasing urbanization, urban-fragmented landscapes are becoming more and more prevalent worldwide. Such fragmentation may lead to small, isolated populations that face great threats from genetic factors that affect even avian species with high dispersal propensities. Yet few studies have investigated the population genetics of species living within urban-fragmented landscapes in the Old World tropics, in spite of the high levels of deforestation and fragmentation within this region. We investigated the evolutionary history and population genetics of the olive-winged bulbul (Pycnonotus plumosus) in Singapore, a highly urbanized island which retains <5% of its original forest cover in fragments. Combining our own collected and sequenced samples with those from the literature, we conducted phylogenetic and population genetic analyses. We revealed high genetic diversity, evidence for population expansion, and potential presence of pronounced gene flow across the population in Singapore. This suggests increased chances of long-term persistence for the olive-winged bulbul and the ecosystem services it provides within this landscape. PMID- 26811777 TI - Environmental controls on the distribution and diversity of lentic Chironomidae (Insecta: Diptera) across an altitudinal gradient in tropical South America. AB - To predict the response of aquatic ecosystems to future global climate change, data on the ecology and distribution of keystone groups in freshwater ecosystems are needed. In contrast to mid- and high-latitude zones, such data are scarce across tropical South America (Neotropics). We present the distribution and diversity of chironomid species using surface sediments of 59 lakes from the Andes to the Amazon (0.1-17 degrees S and 64-78 degrees W) within the Neotropics. We assess the spatial variation in community assemblages and identify the key variables influencing the distributional patterns. The relationships between environmental variables (pH, conductivity, depth, and sediment organic content), climatic data, and chironomid assemblages were assessed using multivariate statistics (detrended correspondence analysis and canonical correspondence analysis). Climatic parameters (temperature and precipitation) were most significant in describing the variance in chironomid assemblages. Temperature and precipitation are both predicted to change under future climate change scenarios in the tropical Andes. Our findings suggest taxa of Orthocladiinae, which show a preference to cold high-elevation oligotrophic lakes, will likely see range contraction under future anthropogenic-induced climate change. Taxa abundant in areas of high precipitation, such as Micropsectra and Phaenopsectra, will likely become restricted to the inner tropical Andes, as the outer tropical Andes become drier. The sensitivity of chironomids to climate parameters makes them important bio-indicators of regional climate change in the Neotropics. Furthermore, the distribution of chironomid taxa presented here is a vital first step toward providing urgently needed autecological data for interpreting fossil chironomid records of past ecological and climate change from the tropical Andes. PMID- 26811778 TI - Ecological differentiation and habitat unsuitability maintaining a ground beetle hybrid zone. AB - Exogenous selection via interactions between organisms and environments may influence the dynamics of hybrid zones between species in multiple ways. Two major models of a hybrid zone allowed us to hypothesize that environmental conditions influence hybrid zone dynamics in two ways. In the first model, an environmental gradient determines the mosaic distribution at the boundary between ecologically differentiated species (mosaic hybrid zone model). In the second model, a patch of unsuitable habitat traps a hybrid zone between species whose hybrids are unfit (tension zone model). To test these, we examined the environmental factors influencing the spatial structure of a hybrid zone between the ground beetles Carabus maiyasanus and C. iwawakianus using GIS-based quantification of environmental factors and a statistical comparison of species distribution models (SDMs). We determined that both of the hypothetical processes can be important in the hybrid zone. We detected interspecific differences in the environmental factors in presence localities and their relative contribution in SDMs. SDMs were not identical between species even within contact areas, but tended to be similar within the range of each species. These results suggest an association between environments and species, and provide evidence that ecological differentiation between species plays a role in the maintenance of the hybrid zone. Contact areas were characterized by a relatively high temperature, low precipitation, and high topological wetness. Thus, the contact areas were regarded as being located in an unsuitable habitat with a drier climate, where those populations are likely to occur in patches with limited precipitation concentrated. A comparison of spatial scales suggests that exogenous selection via environmental factors may be weaker than endogenous selection via genitalic incompatibility. PMID- 26811779 TI - Limitation of seedling growth by potassium and magnesium supply for two ectomycorrhizal tree species of a Central African rain forest and its implication for their recruitment. AB - In the ectomycorrhizal caesalpiniaceous groves of southern Korup National Park, the dominant tree species, Microberlinia bisulcata, displays very poor in situ recruitment compared with its codominant, Tetraberlinia bifoliolata. The reported ex situ experiment tested whether availabilities of soil potassium and magnesium play a role. Seedlings of the two species received applications of K and Mg fertilizer in potted native soil in a local shade house, and their responses in terms of growth and nutrient concentrations were recorded over 2 years. Amended soil concentrations were also determined. Microberlinia responded strongly and positively in its growth to Mg, but less to K; Tetraberlinia responded weakly to both. Added Mg led to strongly increased Mg concentration for Microberlinia while added K changed that concentration only slightly; Tetraberlinia strongly increased its concentration of K with added K, but only somewhat its Mg concentration with added Mg. Additions of Mg and K had small but important antagonistic effects. Microberlinia is Mg-demanding and apparently Mg-limited in Korup soil; Tetraberlinia, whilst K-demanding, appeared not to be K-limited (for growth). Added K enhanced plant P concentrations of both species. Extra applied Mg may also be alleviating soil aluminum toxicity, and hence improving growth indirectly and especially to the benefit of Microberlinia. Mg appears to be essential for Microberlinia seedling growth and its low soil availability in grove soils at Korup may be an important contributing factor to its poor recruitment. Microberlinia is highly shade-intolerant and strongly light responding, whilst Tetraberlinia is more shade-tolerant and moderately light responding, which affords an interesting contrast with respect to their differing responses to Mg supply. The study revealed novel aspects of functional traits and likely niche-partitioning among ectomycorrhizal caesalps in African rain forests. Identifying the direct and interacting indirect effects of essential elements on tropical tree seedling growth presents a considerable challenge due the complex nexus of causes involved. PMID- 26811780 TI - Where do the treeless tundra areas of northern highlands fit in the global biome system: toward an ecologically natural subdivision of the tundra biome. AB - According to some treatises, arctic and alpine sub-biomes are ecologically similar, whereas others find them highly dissimilar. Most peculiarly, large areas of northern tundra highlands fall outside of the two recent subdivisions of the tundra biome. We seek an ecologically natural resolution to this long-standing and far-reaching problem. We studied broad-scale patterns in climate and vegetation along the gradient from Siberian tundra via northernmost Fennoscandia to the alpine habitats of European middle-latitude mountains, as well as explored those patterns within Fennoscandian tundra based on climate-vegetation patterns obtained from a fine-scale vegetation map. Our analyses reveal that ecologically meaningful January-February snow and thermal conditions differ between different types of tundra. High precipitation and mild winter temperatures prevail on middle-latitude mountains, low precipitation and usually cold winters prevail on high-latitude tundra, and Scandinavian mountains show intermediate conditions. Similarly, heath-like plant communities differ clearly between middle latitude mountains (alpine) and high-latitude tundra vegetation, including its altitudinal extension on Scandinavian mountains. Conversely, high abundance of snowbeds and large differences in the composition of dwarf shrub heaths distinguish the Scandinavian mountain tundra from its counterparts in Russia and the north Fennoscandian inland. The European tundra areas fall into three ecologically rather homogeneous categories: the arctic tundra, the oroarctic tundra of northern heights and mountains, and the genuinely alpine tundra of middle latitude mountains. Attempts to divide the tundra into two sub-biomes have resulted in major discrepancies and confusions, as the oroarctic areas are included in the arctic tundra in some biogeographic maps and in the alpine tundra in others. Our analyses based on climate and vegetation criteria thus seem to resolve the long-standing biome delimitation problem, help in consistent characterization of research sites, and create a basis for further biogeographic and ecological research in global tundra environments. PMID- 26811781 TI - Disentangling the influences of mean body size and size structure on ecosystem functioning: an example of nutrient recycling by a non-native crayfish. AB - Body size is a fundamental functional trait that can be used to forecast individuals' responses to environmental change and their contribution to ecosystem functioning. However, information on the mean and variation of size distributions often confound one another when relating body size to aggregate functioning. Given that size-based metrics are used as indicators of ecosystem status, it is important to identify the specific aspects of size distributions that mediate ecosystem functioning. Our goal was to simultaneously account for the mean, variance, and shape of size distributions when relating body size to aggregate ecosystem functioning. We take advantage of habitat-specific differences in size distributions to estimate nutrient recycling by a non-native crayfish using mean-field and variance-incorporating approaches. Crayfishes often substantially influence ecosystem functioning through their omnivorous role in aquatic food webs. As predicted from Jensen's inequality, considering only the mean body size of crayfish overestimated aggregate effects on ecosystem functioning. This bias declined with mean body size such that mean-field and variance-incorporating estimates of ecosystem functioning were similar for samples at mean body sizes >7.5 g. At low mean body size, mean-field bias in ecosystem functioning mismatch predictions from Jensen's inequality, likely because of the increasing skewness of the size distribution. Our findings support the prediction that variance around the mean can alter the relationship between body size and ecosystem functioning, especially at low mean body size. However, methods to account for mean-field bias performed poorly in samples with highly skewed distributions, indicating that changes in the shape of the distribution, in addition to the variance, may confound mean-based estimates of ecosystem functioning. Given that many biological functions scale allometrically, explicitly defining and experimentally or statistically isolating the effects of the mean, variance, and shape of size distributions is necessary to begin generalizing relationships between animal body size and ecosystem functioning. PMID- 26811782 TI - Paleodistribution modeling suggests glacial refugia in Scandinavia and out-of Tibet range expansion of the Arctic fox. AB - Quaternary glacial cycles have shaped the geographic distributions and evolution of numerous species in the Arctic. Ancient DNA suggests that the Arctic fox went extinct in Europe at the end of the Pleistocene and that Scandinavia was subsequently recolonized from Siberia, indicating inability to track its habitat through space as climate changed. Using ecological niche modeling, we found that climatically suitable conditions for Arctic fox were found in Scandinavia both during the last glacial maximum (LGM) and the mid-Holocene. Our results are supported by fossil occurrences from the last glacial. Furthermore, the model projection for the LGM, validated with fossil records, suggested an approximate distance of 2000 km between suitable Arctic conditions and the Tibetan Plateau well within the dispersal distance of the species, supporting the recently proposed hypothesis of range expansion from an origin on the Tibetan Plateau to the rest of Eurasia. The fact that the Arctic fox disappeared from Scandinavia despite suitable conditions suggests that extant populations may be more sensitive to climate change than previously thought. PMID- 26811783 TI - Quantifying interspecific variation in dispersal ability of noctuid moths using an advanced tethered flight technique. AB - Dispersal plays a crucial role in many aspects of species' life histories, yet is often difficult to measure directly. This is particularly true for many insects, especially nocturnal species (e.g. moths) that cannot be easily observed under natural field conditions. Consequently, over the past five decades, laboratory tethered flight techniques have been developed as a means of measuring insect flight duration and speed. However, these previous designs have tended to focus on single species (typically migrant pests), and here we describe an improved apparatus that allows the study of flight ability in a wide range of insect body sizes and types. Obtaining dispersal information from a range of species is crucial for understanding insect population dynamics and range shifts. Our new laboratory tethered flight apparatus automatically records flight duration, speed, and distance of individual insects. The rotational tethered flight mill has very low friction and the arm to which flying insects are attached is extremely lightweight while remaining rigid and strong, permitting both small and large insects to be studied. The apparatus is compact and thus allows many individuals to be studied simultaneously under controlled laboratory conditions. We demonstrate the performance of the apparatus by using the mills to assess the flight capability of 24 species of British noctuid moths, ranging in size from 12 27 mm forewing length (~40-660 mg body mass). We validate the new technique by comparing our tethered flight data with existing information on dispersal ability of noctuids from the published literature and expert opinion. Values for tethered flight variables were in agreement with existing knowledge of dispersal ability in these species, supporting the use of this method to quantify dispersal in insects. Importantly, this new technology opens up the potential to investigate genetic and environmental factors affecting insect dispersal among a wide range of species. PMID- 26811784 TI - A sampling optimization analysis of soil-bugs diversity (Crustacea, Isopoda, Oniscidea). AB - Biological diversity analysis is among the most informative approaches to describe communities and regional species compositions. Soil ecosystems include large numbers of invertebrates, among which soil bugs (Crustacea, Isopoda, Oniscidea) play significant ecological roles. The aim of this study was to provide advices to optimize the sampling effort, to efficiently monitor the diversity of this taxon, to analyze its seasonal patterns of species composition, and ultimately to understand better the coexistence of so many species over a relatively small area. Terrestrial isopods were collected at the Natural Reserve "Saline di Trapani e Paceco" (Italy), using pitfall traps monthly monitored over 2 years. We analyzed parameters of alpha- and beta-diversity and calculated a number of indexes and measures to disentangle diversity patterns. We also used various approaches to analyze changes in biodiversity over time, such as distributions of species abundances and accumulation and rarefaction curves. As concerns species richness and total abundance of individuals, spring resulted the best season to monitor Isopoda, to reduce sampling efforts, and to save resources without losing information, while in both years abundances were maximum between summer and autumn. This suggests that evaluations of beta-diversity are maximized if samples are first collected during the spring and then between summer and autumn. Sampling during these coupled seasons allows to collect a number of species close to the gamma-diversity (24 species) of the area. Finally, our results show that seasonal shifts in community composition (i.e., dynamic fluctuations in species abundances during the four seasons) may minimize competitive interactions, contribute to stabilize total abundances, and allow the coexistence of phylogenetically close species within the ecosystem. PMID- 26811785 TI - Squares of different sizes: effect of geographical projection on model parameter estimates in species distribution modeling. AB - In species distribution analyses, environmental predictors and distribution data for large spatial extents are often available in long-lat format, such as degree raster grids. Long-lat projections suffer from unequal cell sizes, as a degree of longitude decreases in length from approximately 110 km at the equator to 0 km at the poles. Here we investigate whether long-lat and equal-area projections yield similar model parameter estimates, or result in a consistent bias. We analyzed the environmental effects on the distribution of 12 ungulate species with a northern distribution, as models for these species should display the strongest effect of projectional distortion. Additionally we choose four species with entirely continental distributions to investigate the effect of incomplete cell coverage at the coast. We expected that including model weights proportional to the actual cell area should compensate for the observed bias in model coefficients, and similarly that using land coverage of a cell should decrease bias in species with coastal distribution. As anticipated, model coefficients were different between long-lat and equal-area projections. Having progressively smaller and a higher number of cells with increasing latitude influenced the importance of parameters in models, increased the sample size for the northernmost parts of species ranges, and reduced the subcell variability of those areas. However, this bias could be largely removed by weighting long-lat cells by the area they cover, and marginally by correcting for land coverage. Overall we found little effect of using long-lat rather than equal-area projections in our analysis. The fitted relationship between environmental parameters and occurrence probability differed only very little between the two projection types. We still recommend using equal-area projections to avoid possible bias. More importantly, our results suggest that the cell area and the proportion of a cell covered by land should be used as a weight when analyzing distribution of terrestrial species. PMID- 26811786 TI - Dissecting geographic variation in population synchrony using the common vole in central Europe as a test bed. AB - Spatial synchrony of population fluctuations is ubiquitous in nature. Theoretical models suggest that correlated environmental stochasticity, dispersal, and trophic interactions are important promoters of synchrony in nature to leave characteristic signatures of distance-dependent decays in synchrony. Recent refinements of this theory have clarified how distance-decay curves may steepen if local dynamics are governed by different density-dependent feedbacks and how synchrony should vary regionally if the importance and correlation of environmental stochasticity is location-specific. We analysed spatiotemporal data for the common vole, Microtus arvalis from 49 districts in the Czech Republic to examine the pattern of population synchrony between 2000 and 2014. By extending the nonparametric covariation function, we develop a quantitative method that allows a dissection of the effects of distance and additional variables such as altitude on synchrony. To examine the pattern of local synchrony, we apply the noncentered local-indicators of spatial association (ncLISA) which highlights areas with different degrees of synchrony than expected by the region-wide average. Additionally, in order to understand the obtained pattern of local spatial correlations, we have regressed LISA results against the proportion of forest in each district. The common vole abundances fluctuated strongly and exhibited synchronous dynamics with the typical tendency for a decline of synchrony with increasing distance but, not with altitude. The correlation between the neighbor districts decreases as the proportion of forest increases. Forested areas are suboptimum habitats and are strongly avoided by common voles. The investigation of spatiotemporal dynamics in animal populations is a key issue in ecology. Although the majority of studies are focused on testing hypotheses about which mechanisms are involved in shaping this dynamics it is crucial to understand the sources of variation involved in order to understand the underlying processes. PMID- 26811787 TI - Discovering hidden biodiversity: the use of complementary monitoring of fish diet based on DNA barcoding in freshwater ecosystems. AB - Ecological monitoring contributes to the understanding of complex ecosystem functions. The diets of fish reflect the surrounding environment and habitats and may, therefore, act as useful integrating indicators of environmental status. It is, however, often difficult to visually identify items in gut contents to species level due to digestion of soft-bodied prey beyond visual recognition, but new tools rendering this possible are now becoming available. We used a molecular approach to determine the species identities of consumed diet items of an introduced generalist feeder, brown trout (Salmo trutta), in 10 Tasmanian lakes and compared the results with those obtained from visual quantification of stomach contents. We obtained 44 unique taxa (OTUs) belonging to five phyla, including seven classes, using the barcode of life approach from cytochrome oxidase I (COI). Compared with visual quantification, DNA analysis showed greater accuracy, yielding a 1.4-fold higher number of OTUs. Rarefaction curve analysis showed saturation of visually inspected taxa, while the curves from the DNA barcode did not saturate. The OTUs with the highest proportions of haplotypes were the families of terrestrial insects Formicidae, Chrysomelidae, and Torbidae and the freshwater Chironomidae. Haplotype occurrence per lake was negatively correlated with lake depth and transparency. Nearly all haplotypes were only found in one fish gut from a single lake. Our results indicate that DNA barcoding of fish diets is a useful and complementary method for discovering hidden biodiversity. PMID- 26811788 TI - Dynamic changes in host-virus interactions associated with colony founding and social environment in fire ant queens (Solenopsis invicta). AB - The dynamics of host-parasite interactions can change dramatically over the course of a chronic infection as the internal (physiological) and external (environmental) conditions of the host change. When queens of social insects found a colony, they experience changes in both their physiological state (they develop their ovaries and begin laying eggs) and the social environment (they suddenly stop interacting with the other members of the mother colony), making this an excellent model system for examining how these factors interact with chronic infections. We investigated the dynamics of host-viral interactions in queens of Solenopsis invicta (fire ant) as they transition from mating to colony founding/brood rearing to the emergence of the first workers. We examined these dynamics in naturally infected queens in two different social environments, where queens either founded colonies as individuals or as pairs. We hypothesized that stress associated with colony founding plays an important role in the dynamics of host-parasite interactions. We also hypothesized that different viruses have different modalities of interaction with the host that can be quantified by physiological measures and genomic analysis of gene expression in the host. We found that the two most prevalent viruses, SINV-1 and SINV-2, are associated with different fitness costs that are mirrored by different patterns of gene expression in the host. In fact SINV-2, the virus that imposes the significant reduction of a queen's reproductive output is also associated with larger changes of global gene expression in the host. These results show the complexity of interactions between S. invicta and two viral parasites. Our findings also show that chronic infections by viral parasites in insects are dynamic processes that may pose different challenges in the host, laying the groundwork for interesting ecological and evolutionary considerations. PMID- 26811789 TI - Effects of ambient noise on detectability and localization of avian songs and tones by observers in grasslands. AB - Probability of detection and accuracy of distance estimates in aural avian surveys may be affected by the presence of anthropogenic noise, and this may lead to inaccurate evaluations of the effects of noisy infrastructure on wildlife. We used arrays of speakers broadcasting recordings of grassland bird songs and pure tones to assess the probability of detection, and localization accuracy, by observers at sites with and without noisy oil and gas infrastructure in south central Alberta from 2012 to 2014. Probability of detection varied with species and with speaker distance from transect line, but there were few effects of noisy infrastructure. Accuracy of distance estimates for songs and tones decreased as distance to observer increased, and distance estimation error was higher for tones at sites with infrastructure noise. Our results suggest that quiet to moderately loud anthropogenic noise may not mask detection of bird songs; however, errors in distance estimates during aural surveys may lead to inaccurate estimates of avian densities calculated using distance sampling. We recommend caution when applying distance sampling if most birds are unseen, and where ambient noise varies among treatments. PMID- 26811790 TI - Seed viability and germination success of Acacia tortilis along land-use and aridity gradients in the Eastern Sahara. AB - Our study focuses on the keystone species Acacia tortilis and is the first to investigate the effect of domestic ungulates and aridity on seed viability and germination over an extensive part of the Eastern Sahara. Bruchids infest its seeds and reduce their viability and germination, but ingestion by ruminant herbivores diminishes infestation levels and enhances/promotes seed viability and germination. The degree of these effects seems to be correlated with animal body mass. Significantly reduced numbers of wild ruminant ungulates have increased the potential importance of domestic animals and pastoral nomadism for the functionality of arid North African and Middle Eastern ecosystems. We sampled seeds (16,543) from A. tortilis in eight areas in three regions with different aridity and land use. We tested the effect of geography and sampling context on seed infestation using random effects logistic regressions. We did a randomized and balanced germination experiment including 1193 seeds, treated with different manure. Germination time and rates across geography, sampling context, and infestation status were analyzed using time-to-event analyses, Kaplan-Meier curves and proportional hazards Cox regressions. Bruchid infestation is very high (80%), and the effects of context are significant. Neither partial infestation nor adding manure had a positive effect on germination. There is a strong indication that intact, uningested seeds from acacia populations in the extremely arid Western Desert germinate more slowly and have a higher fraction of hard seeds than in the Eastern Desert and the Red Sea Hills. For ingested seeds in the pastoralist areas we find that intact seeds from goat dung germinate significantly better than those from camel dung. This is contrary to the expected body-mass effect. There is no effect of site or variation in tribal management. PMID- 26811791 TI - Weak coordination among petiole, leaf, vein, and gas-exchange traits across Australian angiosperm species and its possible implications. AB - Close coordination between leaf gas exchange and maximal hydraulic supply has been reported across diverse plant life forms. However, it has also been suggested that this relationship may become weak or break down completely within the angiosperms. We examined coordination between hydraulic, leaf vein, and gas exchange traits across a diverse group of 35 evergreen Australian angiosperms, spanning a large range in leaf structure and habitat. Leaf-specific conductance was calculated from petiole vessel anatomy and was also measured directly using the rehydration technique. Leaf vein density (thought to be a determinant of gas exchange rate), maximal stomatal conductance, and net CO 2 assimilation rate were also measured for most species (n = 19-35). Vein density was not correlated with leaf-specific conductance (either calculated or measured), stomatal conductance, nor maximal net CO 2 assimilation, with r (2) values ranging from 0.00 to 0.11, P values from 0.909 to 0.102, and n values from 19 to 35 in all cases. Leaf specific conductance calculated from petiole anatomy was weakly correlated with maximal stomatal conductance (r (2) = 0.16; P = 0.022; n = 32), whereas the direct measurement of leaf-specific conductance was weakly correlated with net maximal CO 2 assimilation (r (2) = 0.21; P = 0.005; n = 35). Calculated leaf specific conductance, xylem ultrastructure, and leaf vein density do not appear to be reliable proxy traits for assessing differences in rates of gas exchange or growth across diverse sets of evergreen angiosperms. PMID- 26811792 TI - Genotype-environment associations support a mosaic hybrid zone between two tidal marsh birds. AB - Local environmental features can shape hybrid zone dynamics when hybrids are bounded by ecotones or when patchily distributed habitat types lead to a corresponding mosaic of genotypes. We investigated the role of marsh-level characteristics in shaping a hybrid zone between two recently diverged avian taxa - Saltmarsh (Ammodramus caudacutus) and Nelson's (A. nelsoni) sparrows. These species occupy different niches where allopatric, with caudacutus restricted to coastal marshes and nelsoni found in a broader array of wetland and grassland habitats and co-occur in tidal marshes in sympatry. We determined the influence of habitat types on the distribution of pure and hybrid sparrows and assessed the degree of overlap in the ecological niche of each taxon. To do this, we sampled and genotyped 305 sparrows from 34 marshes across the hybrid zone and from adjacent regions. We used linear regression to test for associations between marsh characteristics and the distribution of pure and admixed sparrows. We found a positive correlation between genotype and environmental variables with a patchy distribution of genotypes and habitats across the hybrid zone. Ecological niche models suggest that the hybrid niche was more similar to that of A. nelsoni and habitat suitability was influenced strongly by distance from coastline. Our results support a mosaic model of hybrid zone maintenance, suggesting a role for local environmental features in shaping the distribution and frequency of pure species and hybrids across space. PMID- 26811794 TI - Community dynamics of nematodes after Larsen ice-shelf collapse in the eastern Antarctic Peninsula. AB - Free-living marine nematode communities of the Larsen B embayment at the eastern Antarctic Peninsula were investigated to provide insights on their response and colonization rate after large-scale ice-shelf collapse. This study compares published data on the post-collapse situation from 2007 with new material from 2011, focusing on two locations in the embayment that showed highly divergent communities in 2007 and that are characterized by a difference in timing of ice shelf breakup. Data from 2007 exposed a more diverse community at outer station B.South, dominated by the genus Microlaimus. On the contrary, station B.West in the inner part of Larsen B was poor in both numbers of individuals and genera, with dominance of a single Halomonhystera species. Re-assessment of the situation in 2011 showed that communities at both stations diverged even more, due to a drastic increase in Halomonhystera at B.West compared to relatively little change at B.South. On a broader geographical scale, it seems that B.South gradually starts resembling other Antarctic shelf communities, although the absence of the genus Sabatieria and the high abundance of Microlaimus still set it apart nine years after the main Larsen B collapse. In contrast, thriving of Halomonhystera at B.West further separates its community from other Antarctic shelf areas. PMID- 26811793 TI - Inbreeding depression of sperm traits in the zebra finch Taeniopygia guttata. AB - Inbreeding depression, or the reduction in fitness due to mating between close relatives, is a key issue in biology today. Inbreeding negatively affects many fitness-related traits, including survival and reproductive success. Despite this, very few studies have quantified the effects of inbreeding on vertebrate gamete traits under controlled breeding conditions using a full-sib mating approach. Here, we provide comprehensive evidence for the negative effect of inbreeding on sperm traits in a bird, the zebra finch Taeniopygia guttata. We compared sperm characteristics of both inbred (pedigree F = 0.25) and outbred (pedigree F = 0) individuals from two captive populations, one domesticated and one recently wild-derived, raised under standardized conditions. As normal spermatozoa morphology did not differ consistently between inbred and outbred individuals, our study confirms the hypothesis that sperm morphology is not particularly susceptible to inbreeding depression. Inbreeding did, however, lead to significantly lower sperm motility and a substantially higher percentage of abnormal spermatozoa in ejaculate. These results were consistent across both study populations, confirming the generality and reliability of our findings. PMID- 26811795 TI - Plant functional diversity enhances associations of soil fungal diversity with vegetation and soil in the restoration of semiarid sandy grassland. AB - The trait-based approach shows that plant functional diversity strongly affects ecosystem properties. However, few empirical studies show the relationship between soil fungal diversity and plant functional diversity in natural ecosystems. We investigated soil fungal diversity along a restoration gradient of sandy grassland (mobile dune, semifixed dune, fixed dune, and grassland) in Horqin Sand Land, northern China, using the denaturing gradient gel electrophoresis of 18S rRNA and gene sequencing. We also examined associations of soil fungal diversity with plant functional diversity reflected by the dominant species' traits in community (community-weighted mean, CWM) and the dispersion of functional trait values (FD is). We further used the structure equation model (SEM) to evaluate how plant richness, biomass, functional diversity, and soil properties affect soil fungal diversity in sandy grassland restoration. Soil fungal richness in mobile dune and semifixed dune was markedly lower than those of fixed dune and grassland (P < 0.05). Soil fungal richness was positively associated with plant richness, biomass, CWM plant height, and soil gradient aggregated from the principal component analysis, but SEM results showed that plant richness and CWM plant height determined by soil properties were the main factors exerting direct effects. Soil gradient increased fungal richness through indirect effect on vegetation rather than direct effect. The negative indirect effect of FDis on soil fungal richness was through its effect on plant biomass. Our final SEM model based on plant functional diversity explained nearly 70% variances of soil fungal richness. Strong association of soil fungal richness with the dominant species in the community supported the mass ratio hypothesis. Our results clearly highlight the role of plant functional diversity in enhancing associations of soil fungal diversity with community structure and soil properties in sandy grassland ecosystems. PMID- 26811796 TI - A limit on the extent to which increased egg size can compensate for a poor postnatal environment revealed experimentally in the burying beetle, Nicrophorus vespilloides. AB - It is often assumed that there is a positive relationship between egg size and offspring fitness. However, recent studies have suggested that egg size has a greater effect on offspring fitness in low-quality environments than in high quality environments. Such observations suggest that mothers may compensate for poor posthatching environments by increasing egg size. In this paper we test whether there is a limit on the extent to which increased egg size can compensate for the removal of posthatching parental care in the burying beetle, Nicrophorus vespilloides. Previous experiments with N. vespilloides suggest that an increased egg size can compensate for a relatively poor environment after hatching. Here, we phenotypically engineered female N. vespilloides to produce large or small eggs by varying the amount of time they were allowed to feed on the carcass as larvae. We then tested whether differences between these groups in egg size translated into differences in larval performance in a harsh postnatal environment that excluded parental care. We found that females engineered to produce large eggs did not have higher breeding success, and nor did they produce larger larvae than females engineered to produce small eggs. These results suggest that there is a limit on the extent to which increased maternal investment in egg size can compensate for a poor posthatching environment. We discuss the implication of our results for a recent study showing that experimental N. vespilloides populations can adapt rapidly to the absence of posthatching parental care. PMID- 26811797 TI - On the selection of thresholds for predicting species occurrence with presence only data. AB - Presence-only data present challenges for selecting thresholds to transform species distribution modeling results into binary outputs. In this article, we compare two recently published threshold selection methods (maxSSS and maxF pb) and examine the effectiveness of the threshold-based prevalence estimation approach. Six virtual species with varying prevalence were simulated within a real landscape in southeastern Australia. Presence-only models were built with DOMAIN, generalized linear model, Maxent, and Random Forest. Thresholds were selected with two methods maxSSS and maxF pb with four presence-only datasets with different ratios of the number of known presences to the number of random points (KP-RP ratio). Sensitivity, specificity, true skill statistic, and F measure were used to evaluate the performance of the results. Species prevalence was estimated as the ratio of the number of predicted presences to the total number of points in the evaluation dataset. Thresholds selected with maxF pb varied as the KP-RP ratio of the threshold selection datasets changed. Datasets with the KP-RP ratio around 1 generally produced better results than scores distant from 1. Results produced by We conclude that maxFpb had specificity too low for very common species using Random Forest and Maxent models. In contrast, maxSSS produced consistent results whichever dataset was used. The estimation of prevalence was almost always biased, and the bias was very large for DOMAIN and Random Forest predictions. We conclude that maxF pb is affected by the KP-RP ratio of the threshold selection datasets, but maxSSS is almost unaffected by this ratio. Unbiased estimations of prevalence are difficult to be determined using the threshold-based approach. PMID- 26811798 TI - High richness of ectomycorrhizal fungi and low host specificity in a coastal sand dune ecosystem revealed by network analysis. AB - Ectomycorrhizal (EM) fungi are ubiquitous in temperate and boreal forests, comprising over 20,000 species forming root symbiotic associations with Pinaceae and woody angiosperms. As much as 100 different EM fungal species can coexist and interact with the same tree species, forming complex multispecies networks in soils. The degree of host specificity and structural properties of these interaction networks (e.g., nestedness and modularity) may influence plant and fungal community assembly and species coexistence, yet their structure has been little studied in northern coniferous forests, where trees depend on EM fungi for nutrient acquisition. We used high-throughput sequencing to characterize the composition and diversity of bulk soil and root-associated fungal communities in four co-occurring Pinaceae in a relic foredune plain located at Iles de la Madeleine, Quebec, Canada. We found high EM fungal richness across the four hosts, with a total of 200 EM operational taxonomic units (OTUs), mainly belonging to the Agaricomycetes. Network analysis revealed an antinested pattern in both bulk soil and roots EM fungal communities. However, there was no detectable modularity (i.e., subgroups of interacting species) in the interaction networks, indicating a low level of specificity in these EM associations. In addition, there were no differences in EM fungal OTU richness or community structure among the four tree species. Limited shared resources and competitive exclusion typically restrict the number of taxa coexisting within the same niche. As such, our finding of high EM fungal richness and low host specificity highlights the need for further studies to determine the mechanisms enabling such a large number of EM fungal species to coexist locally on the same hosts. PMID- 26811799 TI - Retraction: "Screening of candidate genes and fine mapping of drought tolerance quantitative trait loci on chromosome 4 in rice (Oryza sativa L.) under drought stress" by Nie, Y. Y., L. Zhang, Y. H. Wu, H. J. Liu, W. W. Mao, J. Du, et al. AB - The above article, published online on 15 October 2015 in Wiley Online Library (http://onlinelibrary.wiley.com/doi/10.1002/ece3.1786/abstract), has been retracted by agreement between the authors, the journal Editor in Chief, Allen Moore, and John Wiley & Sons Ltd. The authors have requested the retraction of their paper because they mistakenly analyzed the wrong backcross lines. This mistake was only recently discovered and they are now in the process of repeating the experiment using the correct Backcross Introgression Lines. The authors apologize for this mistake. REFERENCE: Nie, Y. Y., L. Zhang, Y. H. Wu, H. J. Liu, W. W. Mao, J. Du, et al. 2015. Screening of candidate genes and fine mapping of drought tolerance quantitative trait loci on chromosome 4 in rice (Oryza sativa L.) under drought stress. Ecology and Evolution 5(21):5007-5015. doi: 10.1002/ece3.1786. [This retracts the article DOI: 10.1002/ece3.1786.]. PMID- 26811800 TI - Intraspecific variation in defense against a generalist lepidopteran herbivore in populations of Eruca sativa (Mill.). AB - Populations of Eruca sativa (Brassicaceae) from desert and Mediterranean (Med) habitats in Israel differ in their defense against larvae of the generalist Spodoptera littoralis but not the specialist Pieris brassicae. Larvae of the generalist insect feeding on plants of the Med population gained significantly less weight than those feeding on the desert plants, and exogenous application of methyl jasmonate (MJ) on leaves of the Med plants significantly reduced the level of damage created by the generalist larvae. However, MJ treatment significantly induced resistance in plants of the desert population, whereas the generalist larvae caused similar damage to MJ-induced and noninduced plants. Analyses of glucosinolates and expression of genes in their synthesis pathway indicated that defense in plants of the Med population against the generalist insect is governed by the accumulation of glucosinolates. In plants of the desert population, trypsin proteinase inhibitor activity was highly induced in response to herbivory by S. littoralis. Analysis of genes in the defense-regulating signaling pathways suggested that in response to herbivory, differences between populations in the induced levels of jasmonic acid, ethylene, and salicylic acid mediate the differential defenses against the insect. In addition, expression analysis of myrosinase-associated protein NSP2 suggested that in plants of the desert population, glucosinolates breakdown products were primarily directed to nitrile production. We suggest that proteinase inhibitors provide an effective defense in the desert plants, in which glucosinolate production is directed to the less toxic nitriles. The ecological role of nitrile production in preventing infestation by specialists is discussed. PMID- 26811802 TI - Mortality in individuals with intellectual disabilities in Finland. AB - OBJECTIVES: This study aimed at ascertaining the standardized mortality ratios (SMR) for those with an intellectual disability (ID) in Finland. MATERIALS AND METHODS: We used the statistical database of the national insurance institution of Finland and Statistics Finland's mean population figures. We determined the number of individuals who received benefits (disability allowance, disability pension, or care allowance for pensioners) due to an ID diagnosis and the number of those whose benefit had been terminated due to death during the years 1996 2011. RESULTS: SMR for females with a mild ID (IQ 50-69) was 2.8 (95% CI: 2.60 3.01) and for males 2.0 (95% CI: 1.88-2.14), and for females with a severe ID (IQ <50) 5.2 (95% CI: 4.99-5.50) and for males 2.6 (95% CI: 2.48-2.72). CONCLUSION: This significant difference in the SMR figures between males and females with ID warrants further research. PMID- 23867975 TI - The 6-Minute Walk Test and Person-Reported Outcomes in Boys with Duchenne Muscular Dystrophy and Typically Developing Controls: Longitudinal Comparisons and Clinically-Meaningful Changes Over One Year. AB - INTRODUCTION: Data is currently lacking anchoring a 30-meter longitudinal change in walking ability by 6-minute walk test (6MWT) in Duchenne muscular dystrophy as a minimal clinically important difference and "clinically meaningful" person reported outcomes (PROs) at differing levels of ambulatory ability. METHODS: We describe correlation between measures, 1-year change in measures, and correlation of 1-year changes between measures for the six-minute walk test (6MWT), 10-meter run/walk velocity, PedsQL and POSNA Pediatric Outcomes Data Collection Instrument (PODCI) in 24 4-12 year old. ambulatory DMD and 36 typical controls, and determine if minimal clinically important differences (MCID) of PROs contribute to different estimates of 6-minute walk distance (6MWD) change at differing levels of ability. RESULTS: PedsQL total and physical function and PODCI global, transfer/mobility and sports/physical function PROs demonstrated significant differences between DMD and controls (p<0.00001). In DMD, 6MWD and 10-meter run/walk velocity were correlated with PODCI domain scores, with the transfer/mobility scale showing the strongest relationship (r=0.79 and r=0.76). In DMD, 6MWD distance and 10-meter run/walk velocity weakly correlated with PedsQL domain scores. In DMD, 6MWD, 10-meter run/walk velocity, and PODCI global and transfer and basic mobility demonstrated significant one-year change and exceeded the amount of change representing MCID. In DMD, 6MWD change highly correlated with change in PODCI global and PODCI transfer/mobility scores (r=0.76 and r=0.93). PODCI global and PODCI transfer/mobility scales provided the best estimates of 6MWT performance. A "meaningful" 4.5 point change in a low PODCI transfer / basic mobility score of 30 to 34.5 was associated with a 5.6m 6MWD change from 150.3 to 155.9m. At PODCI levels closer to normative levels for healthy controls, the change in 6MWD distance associated with a "meaningful" change in PODCI scores was almost 46m. DISCUSSION: At lower levels of function, smaller increases in 6MWD result in meaningful change in quality of life (QoL) instrument scores. At higher levels of function, larger increases may be necessary to achieve the same QoL change score. PMID- 26811804 TI - Design of an FMCW radar baseband signal processing system for automotive application. AB - For a typical FMCW automotive radar system, a new design of baseband signal processing architecture and algorithms is proposed to overcome the ghost targets and overlapping problems in the multi-target detection scenario. To satisfy the short measurement time constraint without increasing the RF front-end loading, a three-segment waveform with different slopes is utilized. By introducing a new pairing mechanism and a spatial filter design algorithm, the proposed detection architecture not only provides high accuracy and reliability, but also requires low pairing time and computational loading. This proposed baseband signal processing architecture and algorithms balance the performance and complexity, and are suitable to be implemented in a real automotive radar system. Field measurement results demonstrate that the proposed automotive radar signal processing system can perform well in a realistic application scenario. PMID- 26811805 TI - A framework for detecting unfolding emergencies using humans as sensors. AB - The advent of online social networks (OSNs) paired with the ubiquitous proliferation of smartphones have enabled social sensing systems. In the last few years, the aptitude of humans to spontaneously collect and timely share context information has been exploited for emergency detection and crisis management. Apart from event-specific features, these systems share technical approaches and architectural solutions to address the issues with capturing, filtering and extracting meaningful information from data posted to OSNs by networks of human sensors. This paper proposes a conceptual and architectural framework for the design of emergency detection systems based on the "human as a sensor" (HaaS) paradigm. An ontology for the HaaS paradigm in the context of emergency detection is defined. Then, a modular architecture, independent of a specific emergency type, is designed. The proposed architecture is demonstrated by an implemented application for detecting earthquakes via Twitter. Validation and experimental results based on messages posted during earthquakes occurred in Italy are reported. PMID- 26811803 TI - The variance shared across forms of childhood trauma is strongly associated with liability for psychiatric and substance use disorders. AB - INTRODUCTION: Forms of childhood trauma tend to co-occur and are associated with increased risk for psychiatric and substance use disorders. Commonly used binary measures of trauma exposure have substantial limitations. METHODS: We performed multigroup confirmatory factor analysis (CFA), separately by sex, using data from the Childhood Trauma (CT) Study's sample of twins and siblings (N = 2594) to derive three first-order factors (childhood physical abuse, childhood sexual abuse, and parental partner abuse) and, as hypothesized, one higher order, childhood trauma factor (CTF) representing a measure of their common variance. RESULTS: CFA produced a good-fitting model in the CT Study; we replicated the model in the Comorbidity and Trauma (CAT) Study's sample (N = 1981) of opioid dependent cases and controls. In both samples, first-order factors are moderately correlated (indicating they measure largely unique, but related constructs) and their loadings on the CTF suggest it provides a reasonable measure of their common variance. We examined the association of CTF score with risk for psychiatric and substance use disorders in these samples and the OZ-ALC GWAS sample (N = 1538) in which CT Study factor loadings were applied. We found that CTF scores are strongly associated with liability for psychiatric and substance use disorders in all three samples; estimates of risk are extremely consistent across samples. CONCLUSIONS: The CTF is a continuous, robust measure that captures the common variance across forms of childhood trauma and provides a means to estimate shared liability while avoiding multicollinearity. PMID- 26811806 TI - Large Biatrial Thrombembolus Caught in Transit across a Patent Foramen Ovale. AB - Background In rare cases of pulmonary embolism, large thrombemboli have been found entrapped in a patent foramen ovale (PFO). Case Description A patient was referred to our center with leg swelling and dyspnea. Electrocardiogram showed sinus tachycardia and right axis deviation. Echocardiography revealed a highly mobile biatrial thrombus entrapped in a PFO extending to both tricuspid and mitral valves and prolapsing into the left ventricle. Urgent surgery for cardiac thrombectomy and PFO closure was performed. Intraoperatively, massive coherent thrombus material was extracted. Conclusion Because of a lack of data, decision making has to rely on clinical judgment rather than evidence. PMID- 26811807 TI - Dual use of peptide mass spectra: Protein atlas and genome annotation. AB - One of the objectives of genome science is the discovery and accurate annotation of all protein-coding genes. Proteogenomics has emerged as a methodology that provides orthogonal information to traditional forms of evidence used for genome annotation. By this method, peptides that are identified via tandem mass spectrometry are used to refine protein-coding gene models. Namely, these peptides are used to confirm the translation of predicted protein-coding genes, as evidence of novel genes or for correction of current gene models. Proteogenomics requires deep and broad sampling of the proteome in order to generate sufficient numbers of unique peptides. Therefore, we propose that proteogenomic projects are designed so that the generated peptides can also be used to create a comprehensive protein atlas that quantitatively catalogues protein abundance changes during development and in response to environmental stimulus. PMID- 26811808 TI - Association between FEN1 Polymorphisms -69G>A and 4150G>T with Susceptibility in Human Disease: A Meta-Analysis. AB - BACKGROUND: As a DNA repair protein, flap endonuclease 1 is a key enzyme in maintaining genomic instability and preventing carcinogenesis. Two single nucleotide polymorphisms (SNPs), -69G>A and 4150G>T are associated with DNA damage. This meta-analysis is to evaluate the genetic effects of FEN1 gene SNPs ( 69G/A and 4150G/T) and the susceptibility to diseases, including glioma risk, breast cancer, lung cancer, keratoconus (KC) and fuchs' endothelial corneal dystrophy (FECD). METHODS: A literature search of PubMed and Embase was conducted to identify all eligible published studies. Five case-control studies were included with a total of 5612 cases and 6703 controls in this meta-analysis. Crude odds ratios (ORs) with their corresponding confidence intervals (95%CI) were used to assess the strength of the association. RESULTS: The FEN1 -69G/A and 4150G/T polymorphisms were significantly associated with the disease risk. Our meta-analysis showed the FEN1 -69GG genotype was correlated to increase risk for the contained diseases compared with the -69AG genotype (OR=0.77, 95%CI=0.71~0.83). Moreover, the FEN1 4150GG genotype could increase diseases risk compared with the 4150TG genotype (OR=0.81, 95%CI=0.75~0.87). CONCLUSION: The variant genotypes of the FEN1 -69G/A and FEN1 4150G/T polymorphisms may be associated with diseases susceptibility. However, more studies are needed to detect the disease risk in different ethnic populations. PMID- 26811810 TI - Prevalence and Risk Factors Associated with Prehypertension by Gender and Age in a Korean Population in the KNHANES 2010-2012. AB - BACKGROUND: Prehypertension frequently progresses into hypertension and is related to an increased risk of cardiovascular disease. We studied the prevalence of prehypertension and their determinants by gender and age. METHODS: The study used nationally representative data from 11,754 participants aged 20-91 years collected between 2010-2012 Korea National Health and Nutrition Examination Surveys (KNHANES). RESULTS: Prehypertension was more prevalent in men than women (aOR = 2.48, CI = 2.11-2.92). Aging was positively associated with prehypertension (40-59 vs. 20-39, aOR = 1.79, CI = 1.55-2.05; 60+ vs. 20-39, aOR = 2.89, CI = 2.35-3.56). In women aged >=60, prehypertension was associated with WC (aOR = 1.04, CI = 1.00-1.07), whereas in both men and women aged 20-39, it was associated with BMI (men, aOR = 1.14, CI = 1.04-1.24; women, aOR = 1.08, CI = 1.01-1.16). In subjects aged 40-59, age (men, aOR = 1.03, CI = 1.01-1.06; women, aOR = 1.05, CI = 1.02-1.07) was the significant factor increasing the risk of prehypertension, whereas smoking (men, aOR = 0.55, CI = 0.38-0.80; women, aOR = 0.43, CI = 0.24-0.76) showed an inverse association with prehypertension. Alcohol intake showed a positive association with prehypertension in only men aged 40-59. CONCLUSION: Our findings suggest that different gender/age groups may have different patterns of risk factors associated with prehypertension. Thus, healthcare providers should consider both gender and age when designing community based interventions for controlling BP and reducing prehypertension. PMID- 26811811 TI - The Relationship between Social Support and Quality of Life: Evidence from a Prospective Study in Chinese Patients with Esophageal Carcinoma. AB - BACKGROUND: We aimed to evaluate the levels of social support in patients with postoperative esophageal carcinoma and potential effect of social support on generic and EC-specific quality of life. METHODS: Overall, 803 Chinese patients with EC were recruited in the high-incidence region- Linzhou in Henan, China for the observation study. We obtained data on European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), disease specific score of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-OES18 (The QLQ-OES18), and social support evaluation score at home visits by a specially trained research team. RESULTS: Aging and low education were negatively predicted total social support scores. A significant correlation (P = 0.000, 9 = 0.000) was found between QOL physical function and either the subjective or the objective dimensions in social supportive system. OES18 eating difficulty was significantly associated with objective support including family intimacy, friendship and community support (P = 0.016, P = 0.001). CONCLUSIONS: The social support team should endorse quality care as integrating community-care management in post-esophagus recovery and meet the need of individual health quality of life. The elders, educational levels and rural farmers are significant to challenge the social supportive delivery in the current model of esophagus cancer care. PMID- 26811809 TI - Prevalence and Cause of Self-Medication in Iran: A Systematic Review and Meta Analysis Article. AB - BACKGROUND: Nowadays self-medication is one of the most common public health issues in many countries, as well as in Iran. According to need to epidemiological information about self-medication, the aim of this study was to systematic review and meta-analysis of prevalence and cause of self-medication in community setting of Iran. METHODS: Required data were collected searching following key words: medication, self-medication, over-the-counter, non prescription, prevalence, epidemiology, etiology, occurrence and Iran in Google Scholar, PubMed, Scopus, Magiran, SID and IranMedex (from 2000 to 2015). To estimate the overall self-medication prevalence, computer software CMA: 2 applied. In order to report the results, forest plot was employed. RESULTS: Out of 1256 articles, 25 articles entered to study. The overall prevalence of self medication based on the random effect model was estimated to be 53% (95% CI, lowest= 42%, highest=67%). The prevalence of self-medication in students was 67% (95% CI, lowest=55%, highest=81%), in the household 36% (95% CI, lowest=17%, highest= 77%) and in the elderly people 68% (95% CI, lowest=54%, highest=84%). The most important cause of self-medication was mild symptoms of disease. The most important group of disease in which patients self-medicated was respiratory diseases and the most important group of medication was analgesics. CONCLUSION: The results show a relatively higher prevalence of self-medication among the Iranian community setting as compared to other countries. Raising public awareness, culture building and control of physicians and pharmacies' performance can have beneficial effects in reduce of prevalence of self-medication. PMID- 26811812 TI - Rape against Brazilian Women: Characteristics of Victims and Sex Offenders. AB - BACKGROUND: Violence against women is a serious social problem and affects mainly young women. This study aimed to evaluate sexual violence against women in Campina Grande, Brazil. METHODS: A retrospective study with analysis of 886 forensic medical reports of sexual violence from the Institute of Legal Medicine of Campina Grande, Brazil, was conducted between January 2005 and December 2009. Sociodemographic variables related to victims, offenders and aggressions were analyzed. Significance level of 5% was adopted. RESULTS: Two hundred and ninety one cases of rape (32.8%) were confirmed, the majority of victims aged between 0 and 19 years (89.9%), were single (98.8%) and had low educational level (86.9%), with association with marital status (P = 0.02). The sex offender was known to the victim in 84.2% of cases and in 93.8% of cases, he acted alone. There was an association between rape and the relationship with the offenders (P = 0.01) and the age of the offenders (P = 0.03). The rape occurred in most cases at the home of victims (49.3%), with the use of violence in 72.3% of cases, but only 5.7% of the victims exhibited physical injuries. There was an association between rape and variables date of occurrence (P = 0.001), previous virginity (P = 0.001) and violence during practice (P = 0.001). CONCLUSION: Over one third of women were victims of rape, predominantly adolescents, unmarried and with low educational level. The offenders were known to the victims, and acted alone in most situations, making use of physical violence. PMID- 26811813 TI - Perception of Lay People Regarding Determinants of Health and Factors Affecting It: An Aggregated Analysis from 29 Countries. AB - BACKGROUND: This study aimed to evaluate the perception of lay people regarding determinants of health at global level and factors affecting it. METHODS: Data was collected from International Social Survey Program (ISSP) and World Bank website. Multilevel regression analysis was done and lay people's perception regarding health behavior, environment, poverty and genes as health determinants was assessed. Various socio demographic factors were used as independent variables. RESULTS: The highest percentage of people agreed environment as determinant of health. An inverse relationship was observed between GNI quartiles and an individual's agreement with poverty, health behavior, and environment as health determinant. There was a significant negative association of females with health damaging behavior (P<0.05) and positive association with environment and genes (P<0.05) as health determinants. Elderly people agreed with poverty as determinant of health (P<0.05). GNI was negatively related to environment (P<0.05) and poverty (P<0.05) as health determinant. CONCLUSION: The common public is now becoming aware of a broadened concept of health and people belonging to different backgrounds have different perceptions regarding determinants of health. Our results show that highest percentage of people agreed with environment as determinant of health, which is consistent with scientific view of increased burden of disease, caused by environmental factors. Thus, tailored health programs and policies that address an individual's specific problems are likely to induce a change in behavior and attitude, hence decreasing the disease burden. PMID- 26811814 TI - Optimized Expression and Purification of Humbug in Pichia pastoris and Its Monoclonal Antibody Preparation. AB - BACKGROUND: The humbug gene is a truncated isoform of Aspartyl beta-hydroxylase (ASPH) gene that is overexpressed in many human malignancies. In recent years, since humbug has received increasing attention, it is considered as a potential therapeutic molecular target. Therefore, it is necessary for preparing humbug protein and its monoclonal antibody to investigate its structure and function. METHOD: The optimized humbug gene, synthesized by Genscript in Nanjing, China on December 21st 2013, was expressed in Pichia pastoris cells that were cultured in a 10-L bioreactor. The recombinant protein was further obtained and purified by using ion exchange chromatography and Sephadex G75. The humbug protein was used to immunize Balb/c mice to generate the monoclonal antibodies. The specificity and sensitivity of the monoclonal antibodies were assessed by indirect enzyme linked immunosorbent assay. Finally, the humbug monoclonal antibodies were used to detect the expression of humbug in several tumor cell lines via indirect immunofluorescence. RESULTS: Firstly, the recombinant humbug was expressed in P. pastoris successfully and efficiently by using a gene-optimized strategy. Secondly, the purification process of humbug was established via multiple chromatography methods. In addition, four monoclonal antibodies against humbug were obtained from the immunized Balb/c mice, and the result of indirect immunofluorescence was indicated that the humbug monoclonal antibody showed the high affinity with humbug protein, which expressed in several tumor cell lines. CONCLUSION: The over-expression of recombinant humbug provides adequate sources for its structural study and the preparation of the humbug-specific monoclonal antibody can potentially be used in tumor initial diagnosis and immunotherapy. PMID- 26811815 TI - Lean Body Mass as a Predictive Value of Hypertension in Young Adults, in Ankara, Turkey. AB - BACKGROUND: The aim of this study was to assess the predictive capacity of body composition estimated by bioelectrical impedance analysis (BIA) to identify abnormal blood pressure in physical education and sport teaching students in the city of Ankara. METHODS: Data for this cross-sectional study were obtained in the city of Ankara in 2014. A total of 133 students aged 20-35 yr participated in this study. Anthropometric measurements were measured. Body composition was assessed by BIA. Physical activity level (PAL) and usual dietary intake were assessed. Pre-hypertension and hypertension were defined, respectively, as BP >=120 and/or 80, and >=140 and /or 90 mmHg. RESULTS: More overweight students showed abnormal BP especially SBP (P=0.005 and 0.002, respectively). Age adjusted regression showed significant association between arm circumference (beta= 0.176, P 0.044), mid arm muscle circumference (MAMC) (beta= 0.235, P 0.007), lean body mass (LBM) (beta= 0.238, P 0.006), basal metabolism rate (BMR) (beta= 0.219, P 0.012) and SBP and, also, MAMC (beta= 0.201, P 0.022), LBM (beta= 0.203, P 0.021), BMR (beta= 0.189, P 0.030) and DBP. Fat intake was associated with DBP (beta= 0.14, P =0.040). Multivariate regression models adjusted for age, BMI, WC and fat intake/kg body weight showed positive association of SBP with MAMC, BMR and LBM (P<0.05). CONCLUSION: The relationship between blood pressure and body composition in young adults may be associated to LBM and MAMC. LBM or MAMC in this population may be indirect indicators of heart muscle mass and heart pumping power. PMID- 26811816 TI - Prevalence of Null Genotypes of Glutathione S-Transferase T1 (GSTT1) and M1 (GSTM1) in Seven Iranian Populations. AB - BACKGROUND: Previous studies have revealed significant differences between populations for genotypic frequencies of glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) polymorphisms. In order to find the frequency of the null genotypes of GSTM1 and GSTT1 in Iranian populations, the present study was carried out. METHODS: The total study subjects consisted of 1340 unrelated healthy Muslims/Iranian. From these 297, 200, 123, 168, 152, 200, and 200 individuals from Tabriz (East Azerbaijan Province; belong to Azaris), Yasuj (Kohgiluyeh-va Boyerahmad Province; belong to Lurs), Abarku (Yazd Province; belong to Persians), Zahedan (Sistan-va-Balouchestan Province; belong to Balouchis), Zahedan (Sistan va-Balouchestan Province; belong to Sistanis), Kermanshah (Kermanshah Province; belong to Kurds), and Gorgan (Golestan Province; belong to Turkmen) respectively. The genotypes were detected by multiplex PCR. RESULTS: The frequency of GSTM1 null genotype among Azaris, Lurs, Persians, Balouchis, Sistanis, Kurds, and Turkmen was 43.8, 50.0, 52.0, 50.0, 51.3, 56.0, and 53.0%, respectively. There was no significant difference between these populations for the genotypic distribution of the GSTM1 polymorphism (chi(2)=8.47, df=6, P=0.206). The frequency of GSTT1 null genotype among Azaris, Lurs, Persians, Balouchis, Sistanis, Kurds, and Turkmen was 18.2, 17.0, 29.3, 20.8, 17.8, 18.5, and 23.0%, respectively. There was very similarity between Azaris, Kurds and Lurs for the frequency of GSTT1 genotypes (chi(2)=0.17, df=2, P=0.916). CONCLUSION: By comparing the frequency of GSTT1 genotypes among Iranian populations, Caucasians and Asians, it is concluded that Azaris, Kurds and Lurs were similar to each other. Taken together, it is suggested that although Azaris are Turkish speaking belong to Caucasians. PMID- 26811817 TI - The Misuse of Anabolic-Androgenic Steroids among Iranian Recreational Male Body Builders and Their Related Psycho-Socio-Demographic factors. AB - BACKGROUND: The high prevalence and potential side effects of anabolic-androgenic steroids (AAS) misuse by athletes has made it a major public health concern. Epidemiological studies on the abuse of such drugs are mandatory for developing effective preventive drug control programs in sports community. This study aimed to investigate the prevalence of AAS abuse and their association with some psycho socio-demographic factors in Iranian male recreational body-builders. METHODS: Between March and October 2011; 906 recreational male body-builders from 103 randomly selected bodybuilding clubs in Tehran, Iran were participated in this study. Some psycho-socio- demographic factors including age, job, average family income, family size, sport experience (months), weekly duration of the sporting activity (h), purpose of participation in sporting activity, mental health as well as body image (via General Health Questionnaire and Multidimensional Body Self Relations Questionnaire, respectively), and history of AAS use were obtained by interviews using questionnaires. RESULTS: Participants were all recreational male body-builders [mean age (SD): 25.7 (7.1), ranging 14-56 yr]. Self-report of AAS abuse was registered in 150 body-builders (16.6%). Among different psycho socio-demographic factors, only family income and sport experience were inversely associated with AAS abuse. CONCLUSION: Lifetime prevalence of AAS abuse is relatively high among recreational body-builders based on their self-report. Some psycho-socio-demographic factors including family income and sport experience may influence the prevalence of AAS abuse. PMID- 26811818 TI - Assessing the Knowledge, Attitudes, and Practices of Students Regarding Ebola Virus Disease Outbreak. AB - BACKGROUND: The emergence and spread of Ebola outbreak is a growing problem worldwide, which represents a significant threat to public health. Evidence has shown that the level of knowledge, attitude, and practice of people in the society play major roles in controlling the spread of Ebola virus disease. This study was designed to determine knowledge, attitude and practice of students at School of Public Health, Tehran University of Medical Sciences towards Ebola. METHODS: A cross-sectional survey was performed in Tehran, Iran in 2014 using a pretested self-administered questionnaire on a stratified sample of 400 students. Descriptive and multivariate analyses were used for statistical analysis. RESULTS: All-in-all, 385 students returned the completed questionnaires making a response rate of 96.3%., 239 (62.2%) were females and 145 (37.8%) were males. The mean age of female and males were 28.44 and 30.3 years respectively. Of the 385 students, 83 (21.7%) were studying at PhD level, 210 (55.0%) at Masters Level (including MPH) and 89 (23.3%) at Bachelors level. knowledge of the students regarding EVD transmission was lowest among students of Department of Occupational Health (50.0%), followed by Health Education and Promotion Department (33.3%). Virology Department recorded the highest percentage of students who had selected correct answers regarding EVD prevention (100.0%). CONCLUSION: These findings will aid in the assessment of the adequacy of current students' educational curriculum. Also, it will provide further insight in designing future multifaceted interventions to promote specific messages to change attitude and improve practice. PMID- 26811819 TI - Survival Analysis of Breast Cancer Patients after Surgery with an Intermediate Event: Application of Illness-Death Model. AB - BACKGROUND: Breast cancer (BC) is the second most commonly diagnosed cancer after lung cancer. Survival of BC patients is affected by intermediate events. This study was aimed to investigate the disease course of primary nonmetastatic BC patients with first recurrence of the tumor (FRT) as the intermediate event using the illness- death model. METHODS: This retrospective cohort study was conducted on 529 Iranian females with BC underwent surgery, from 1995 to 2013. Patients, tumor and treatment characteristics were collected from medical records of the patients. The illness-death model were used to investigate the relationship between these factors and survival time. Data were analyzed using version 3.1.1 of R software. RESULTS: The risk of FRT in patients who had tumors size in the range of 2-5 cm and >5 cm was 1.3 and 3.5 times higher than that of patients with tumor size <=2 cm, respectively (P<0.001). Furthermore, risk of death in patients aged >=50 years was 1.6 times higher compared to patients aged less than 50 years (P =0.012). Risk of death after metastasis in patients with tumor size >5 cm was 2.1 times higher than patients with tumor size <=2 cm (P =0.019). CONCLUSIONS: The stage of the disease and tumor size have statistically significant effects on patients' survival before occurrence of the FRT. Furthermore, illness-death model was found to be a useful tool in modeling the disease course of BC patients. PMID- 26811820 TI - The Interaction between Heterotrophic Bacteria and Coliform, Fecal Coliform, Fecal Streptococci Bacteria in the Water Supply Networks. AB - BACKGROUND: This study investigated the interaction between heterotrophic bacteria and coliform, fecal coliforms, fecal streptococci bacteria in water supply networks. METHODS: This study was conducted during 2013 on water supply distribution network in Aq Qala City, Golestan Province, Northern Iran and standard methods were applied for microbiological analysis. The surface method was applied to test the heterotrophic bacteria and MPN method was used for coliform, fecal coliform and fecal streptococci bacteria measurements. RESULTS: In 114 samples, heterotrophic bacteria count were over 500 CFU/ml, which the amount of fecal coliform, coliform, and fecal streptococci were 8, 32, and 20 CFU/100 ml, respectively. However, in the other 242 samples, with heterotrophic bacteria count being less than 500 CFU/ml, the amount of fecal coliform, coliform, and fecal streptococci was 7, 23, and 11 CFU/100ml, respectively. The relationship between heterotrophic bacteria, coliforms and fecal streptococci was highly significant (P<0.05). We observed the concentration of coliforms, fecal streptococci bacteria being high, whenever the concentration of heterotrophic bacteria in the water network systems was high. CONCLUSION: Interaction between heterotrophic bacteria and coliform, fecal coliforms, fecal streptococci bacteria in the Aq Qala City water supply networks was not notable. It can be due to high concentrations of organic carbon, bio-films and nutrients, which are necessary for growth, and survival of all microorganisms. PMID- 26811822 TI - Type of Chemotherapy-Induced Peripheral Neuropathy, Influencing Factors, and Functional Status. PMID- 26811821 TI - Detecting Driver Mental Fatigue Based on EEG Alpha Power Changes during Simulated Driving. AB - BACKGROUND: Driver fatigue is one of the major implications in transportation safety and accounted for up to 40% of road accidents. This study aimed to analyze the EEG alpha power changes in partially sleep-deprived drivers while performing a simulated driving task. METHODS: Twelve healthy male car drivers participated in an overnight study. Continuous EEG and EOG records were taken during driving on a virtual reality simulator on a monotonous road. Simultaneously, video recordings from the driver face and behavior were performed in lateral and front views and rated by two trained observers. Moreover, the subjective self assessment of fatigue was implemented in every 10-min interval during the driving using Fatigue Visual Analog Scale (F-VAS). Power spectrum density and fast Fourier transform (FFT) were used to determine the absolute and relative alpha powers in the initial and final 10 minutes of driving. RESULTS: The findings showed a significant increase in the absolute alpha power (P = 0.006) as well as F-VAS scores during the final section of driving (P = 0.001). Meanwhile, video ratings were consistent with subjective self-assessment of fatigue. CONCLUSION: The increase in alpha power in the final section of driving indicates the decrease in the level of alertness and attention and the onset of fatigue, which was consistent with F-VAS and video ratings. The study suggested that variations in alpha power could be a good indicator for driver mental fatigue, but for using as a countermeasure device needed further investigations. PMID- 26811823 TI - Quality of Life and Fatigue among Jordanian Cancer Patients. PMID- 26811825 TI - Prevalence of Work-Related Musculoskeletal Symptoms (WMSS) among the Motorcycle Mechanics of Lahore, Pakistan. PMID- 26811824 TI - Accidental Injury of Chinese Children: Priorities and Actions. PMID- 26811826 TI - Clinical Observation on the Disinfection of Turbine Water System to Minimize Postoperative Complications of Minimally Invasive Tooth Extraction. PMID- 26811827 TI - Perspective of Iranian Vaccine-Preventable Diseases Surveillance System in the Era of Newly Introduced Pentavalent Vaccine: Possibility of Implementing a Sentinel Hospital-Based Surveillance System. PMID- 26811828 TI - Using Advanced Statistical Models to Predict the Non-Communicable Diseases. PMID- 26811829 TI - Iran's Health System and Readiness to Meet the Aging Challenges. PMID- 26811830 TI - Some Facts about Case Fatality of Acute Myocardial Infarction in Iran. PMID- 26811831 TI - Extrapulmonary Tuberculosis Presenting With Isolated Uveitis. PMID- 26811832 TI - Interventions to reduce length of stay and accelerate validated measures of recovery in cardiac surgery. PMID- 26811833 TI - Myocardial recovery during mechanical circulatory support: weaning and explantation criteria. AB - For selected patients ventricular assist device explantation is feasible. Freedom from heart transplantation and VAD support for >15 years following VAD removal is possible even if recovery is incomplete and the underlying cause for ventricular assist device implantation was a chronic form of cardiomyopathy. Echocardiography and rightheart catheterization are necessary to assess cardiac recovery. However, to date there is no gold standard for recovery assessment. Certain echocardiography parameters appeared highly predictive for long-term (>=5 years) post-weaning cardiac function and reliable for weaning decisions. PMID- 26811834 TI - Myocardial recovery during mechanical circulatory support: long-term outcome and elective ventricular assist device implantation to promote recovery as a treatment goal. AB - Even after incomplete myocardial recovery during mechanical circulatory support, long-term survival rates after ventricular assist device (VAD) explantation can be better than those expected after heart transplantation even for patients with chronic non-ischemic cardiomyopathy as the underlying cause for VAD implantation. The elective therapeutic use of ventricular assist devices for heart failure reversal in its early stage is a future goal. It may be possible to achieve it by developing tools to predict heart failure reversibility even before ventricular assist device implantation and increasing the number of weaning candidates by improvement of adjunctive therapies to optimize unloading-promoted recovery. Special attention is focused on the long-term stability of cardiac remission after VAD removal, the clinical relevance unloading-promoted myocardial recovery and on the current knowledge about a potential prediction of myocardial recovery during long-term VAD support already before VAD implantation. PMID- 26811835 TI - A novel non-invasive ventilation mask to prevent and manage respiratory failure during fiberoptic bronchoscopy, gastroscopy and transesophageal echocardiography. AB - Fiberoptic bronchoscopy (for difficult intubation, bronchoalveolar lavage or biopsies), gastric endoscopies and transesophageal echocardiography (for transfemoral aortic valve replacement, MitraClip or left atrial appendage closure), are widespread diagnostic and therapeutic procedures. Non-invasive ventilation during upper endoscopies can be used to prevent or treat acute respiratory failure especially in high risk or sedated patients. We describe a novel full face mask specifically developed not only for "elective" non-invasive ventilation during upper endoscopies but also for emergent application without probe removal. The mask is formed by two halves fixed only at the upper extremity allowing opening and closure while the probe is in place. Position of the port and shape of the mask allow easy insertion (through the nose or the mouth) and handling of different sized probes. The mask, commercialized as "Janus", preserves arterial oxygenation during procedures in spontaneously breathing patients with or at risk of hypoxemia (mainly fiberoptic bronchoscopy for guided tracheal intubation or for bronchoalveolar lavage). In patients requiring a true ventilatory support (like patients with neuromuscular disease or those deeply sedated), Janus also allows effective manual or mechanical ventilation. Its use can improve safety, patient's comfort (as sedation can be titrated to the desired effect without fearing respiratory depression) and efficiency, avoiding time wasting and allowing procedure completion. Prospective trials are required to confirm its effectiveness. PMID- 26811836 TI - The freestyle valve as a right ventricle to pulmonary artery conduit. A systematic review and meta-analysis. AB - INTRODUCTION: Reconstruction of the right ventricular outflow tract is the most commonly performed valve repair/replacement procedure in congenital cardiac surgery. There is an ongoing shortage of homografts, and existing bioprosthetic options suffer from substantial rates of structural valve deterioration over time. The Medtronic Freestyle valve is used extensively in the aortic position, but little data is available on its performance in the pulmonary position. METHODS: A systematic review and meta-analysis of primary studies reporting echocardiographic and clinical outcomes, including reintervention and functional status, associated with the Freestyle valve in the pulmonary position for both Ross and congenital surgery. RESULTS: 13 observational studies including 334 patients with a mean follow-up of 34 months (range 10-98 months) fulfilled the eligibility criteria and were included in the review. Structural valve deterioration occurred in 4.8% (95% confidence interval 0.8-10.6%) of patients. Reintervention was required in 1.1% (95% confidence interval 0.0-3.3%). Freedom from symptoms of heart failure occurred in 97.7% (94.6-99.7%). The results did not change substantially when analysed according to Ross or congenital surgery. CONCLUSIONS: The Freestyle valve performs well at short-term follow-up and provides a viable alternative when homografts are unavailable. Further long-term studies are required to better assess its role in right ventricular outflow tract reconstruction. PMID- 26811837 TI - Impact of immediate versus delayed tracheal extubation on length of ICU stay of cardiac surgical patients, a randomized trial. AB - INTRODUCTION: Ultra-fast track anaesthesia aims at immediate extubation of cardiac surgical patients at the end of the operation. This study compares the effect of ultrafast track anesthesia versus continued postoperative mechanical ventilation on the intensive care unit length of stay. METHODS: Fifty-two elective adult patients were randomly allocated into ultrafast track anaesthesia and conventional groups by computer-generated random numbers. Redo operations, pre-operative intubation, uncontrolled diabetes, shock/left ventricular ejection fraction < 45%, pulmonary artery systolic pressure >55mmHg, creatinine clearance 1, haemodynamic instability, or those with concerns of postoperative bleeding were excluded. Pre- and intra-operative management was similar and Logistic EuroSCORE II was calculated for all. Intra-operatively, haemodynamic parameters, urine output, oxygen saturation, arterial blood gas analysis, 5-lead electrocardiogram, operative bypass- and cross-clamp time, and opioid consumption were collected. Postoperatively, patients were compared during their intensive care unit stay. Data were analysed by chi2/Fischer exact, unpaired student's t test, univariate two-group repeated measures with post hoc Dunnett's test, and Mann-Whitney U tests as appropriate. p < 0.05 was considered significant. RESULTS: Patients were comparable regarding their peri-operative characteristics and EuroSCORE. The intensive care unit stay was shorter in the ultrafast track anaesthesia group [57.4 (18.6) vs. 95 (33.6) h. p < 0.001], without increasing postoperative renal, respiratory complications rate or reopening rate. CONCLUSIONS: In this single center study, ultrafast track anaesthesia decreased intensive care unit stay without increasing the rate of post-operative complications. PMID- 26811838 TI - Pitfalls in percutaneous ECMO cannulation. AB - INTRODUCTION: This observational report depicts typical problems of extracorporeal membrane oxygenation cannulation from a large case series of a single center. METHODS: We analysed our experience with 720 consecutive patients receiving veno-venous or veno-arterial extracorporeal membrane oxygenation focusing on the spectrum of complications occurring in a subset of 159 patients treated with percutaneous veno-arteria extracorporeal membrane oxygenation in our institution between January 2009 to December 2014. RESULTS: The main problems were: vascular complications or ischemia of the corresponding extremity (leading to surgical revision in 16.9 % of patients); blood loss and/or relocation of cannulas. Hypoxia of the upper body (Harlequin syndrome) occurred in 8.8 % of patients. Cannulation failure and malfunction were infrequent. Careful insertion technique, close surveillance and monitoring are compelling. CONCLUSIONS: As lack of experience is the trigger of many complications, adequate training of cannulation techniques is essential to minimize adverse events. PMID- 26811839 TI - Improved detection of an intravascular catheter using dual energy subtraction radiography. PMID- 26811840 TI - Hypothermic lung edema after accidental hypothermia with out of hospital cardiac arrest. PMID- 26811841 TI - Surgical therapy for complications of pneumonia on extracorporeal membrane oxygenation can improve the ability to wean patients from support. PMID- 26811842 TI - Resting energy expenditures in haemodynamically compromised cardiac patients. PMID- 26811844 TI - Role of the Infectious Disease Consultant in Management of Patients With Tuberculosis-Associated Ocular Inflammation. AB - Background. Tuberculosis is a disease with continued worldwide prevalence, morbidity, and mortality. Tuberculosis-associated ocular inflammation (TB-AOI) is a manifestation that can occur with pulmonary or extrapulmonary TB. Evaluation of these ocular presentations and treatment in the United States are limited. Our objective was to describe cases in an urban area and assess the role of the infectious diseases specialist in managing these complex patients. Methods. We performed a retrospective case series of all patients referred to our infectious disease clinic for presumed TB-AOI from 2005 through 2013. Patients with ocular inflammation were determined to have presumed TB-AOI based on clinical presentation with correlative positive tuberculin skin test and/or QuantiFERON-TB Gold. Attempts were made to exclude other diagnoses. Data were collected and analyzed with respect to demographics, ocular manifestations, and treatment. Results. Sixty eyes of 42 patients were included in the study; anterior uveitis was the most common site of involvement. The median age was 46 years, and 33 patients (79%) were foreign born. Forty patients (95%) received a course of antituberculous therapy with 38% experiencing treatment-related side effects. A 6 month duration was recommended in 78% cases. There was improvement or stability of the vision in 42 eyes (74%) of those treated. Conclusions. Ocular involvement is an uncommon but important manifestation of TB. Our data further characterize TB-AOI cases in the United States. Treatment provides significant benefit to properly selected patients. A multidisciplinary approach, with care provided by ophthalmology and infectious disease providers, should be used to allow for the most efficacious treatment. PMID- 26811843 TI - Fatigue Alters Landing Shock Attenuation During a Single-Leg Vertical Drop Jump. AB - BACKGROUND: Landings in fatigue conditions are considered to be one of the factors that cause noncontact anterior cruciate ligament (ACL) injury. Additionally, it is known that fatigue alters lower extremity landing strategies and decreases the ability to attenuate shock during landing. PURPOSE: To determine characteristics of knee kinematics and shock attenuation during the landing phase of a single-leg vertical drop jump in a fatigued condition. The hypothesis was that knee kinematics during the landing phase of a single-leg vertical drop jump would demonstrate a significant difference between before and after fatigue. STUDY DESIGN: Controlled laboratory study. METHODS: Thirty-four college females participated in this experiment. They were randomly assigned to either the fatigue (n = 17) or control group (n = 17). The fatigue group performed the single-leg vertical drop jump before and after the fatigue protocol, which was performed on a bike ergometer. Knee kinematics data were obtained from the 3-dimensional motion analysis system. The ratio of each variable (%) was calculated, comparing the pre- to postfatigue protocol. Unpaired t tests were used to compare changes in kinematic variables between the fatigue induced group and control group. RESULTS: Peak knee flexion angular velocity increased significantly in the fatigue group (106.1% +/- 8.0%) in comparison with the control group (100.7% +/- 6.6%) (P < .05). However, peak knee flexion angle and acceleration had no differences between each group. Peak knee adduction/abduction angle, velocity, and acceleration also had no differences between each group. CONCLUSION: Fatigue decreased the ability to attenuate shock by increasing angular velocity in the direction of knee flexion during single-leg drop jump landing. These findings indicate the need to evaluate the ability to attenuate shock by measuring knee flexion angular velocity when fatigue is considered. CLINICAL RELEVANCE: Measuring knee angular velocity during landings might be an important evaluation parameter in the consideration of the knee injury prevention. PMID- 26811846 TI - Editorial: Orthodontics and overall oral health. PMID- 26811845 TI - Correction of Gradient Nonlinearity Bias in Quantitative Diffusion Parameters of Renal Tissue with Intra Voxel Incoherent Motion. AB - Spatially non-uniform diffusion weighting bias due to gradient nonlinearity (GNL) causes substantial errors in apparent diffusion coefficient (ADC) maps for anatomical regions imaged distant from magnet isocenter. Our previously-described approach allowed effective removal of spatial ADC bias from three orthogonal DWI measurements for mono-exponential media of arbitrary anisotropy. The present work evaluates correction feasibility and performance for quantitative diffusion parameters of the two-component IVIM model for well-perfused and nearly isotropic renal tissue. Sagittal kidney DWI scans of a volunteer were performed on a clinical 3T MRI scanner near isocenter and offset superiorly. Spatially non uniform diffusion weighting due to GNL resulted both in shift and broadening of perfusion-suppressed ADC histograms for off-center DWI relative to unbiased measurements close to isocenter. Direction-average DW-bias correctors were computed based on the known gradient design provided by vendor. The computed bias maps were empirically confirmed by coronal DWI measurements for an isotropic gel flood phantom. Both phantom and renal tissue ADC bias for off-center measurements was effectively removed by applying pre-computed 3D correction maps. Comparable ADC accuracy was achieved for corrections of both b-maps and DWI intensities in presence of IVIM perfusion. No significant bias impact was observed for IVIM perfusion fraction. PMID- 26811847 TI - Electrosurgery and ultrasonics on patients with implantable cardiac devices: Evidence of side effects in the dental practice. AB - OBJECTIVE: Implantable cardiac pacemakers and cardiac defibrillators (ICDs) have been introduced in the care of patients with cardiac dysrhythmias. Most dental practitioners demonstrate extreme caution when treating patients with ICDs. This paper presents a review of the available literature on these devices and how they interact with dental electrosurgery and ultrasonic device use. RESULTS: Based on the analysis of the literature, this view is not corroborated by the current clinical data, and appears to be misguided. While further in-vivo studies are needed to truly determine the true level of risk, the evidence suggests that there is no contraindication for electrosurgery or ultrasonics use in patients with ICDs. CONCLUSION: Using the precautions stated in this analysis, the risk of any deleterious effect on ICD function is minimal. PMID- 26811848 TI - Microballoon pressure sensors for particle imaging manometry in liquid and gaseous media. AB - We present the fabrication and testing of engineered microballoon particles that expand and contract under external pressure changes hence serving as microscopic pressure sensors. The particles consist of 12 MUm hollow flexible 0.4 MUm-thick parylene-C shells with and without a coating of ultrathin Al2O3 diffusion barriers, and the changes in the particle radius are measured from the particle spectral reflectivity. The microballoons display radial pressure sensitivities of 0.64 nm psi(-1) and 0.44 nm psi(-1), respectively in agreement with theoretical estimates. The microballoon devices were used for mapping the internal pressure drop within microfluidic chips. These devices experience nearly spherical symmetry which could make them potential flow-through sensors for the augmentation of particle-based flow characterization methodologies extending today's capabilities of particle imaging velocimetry. PMID- 26811849 TI - Lab on a chip sensor for rapid detection and antibiotic resistance determination of Staphylococcus aureus. AB - The Gram-positive bacterium, Staphylococcus aureus (S. aureus), is a major pathogen responsible for a variety of infectious diseases ranging from cellulitis to more serious conditions such as septic arthritis and septicaemia. Timely treatment with appropriate antibiotic therapy is essential to ensure clinical defervescence and to prevent further complications such as infective endocarditis or organ impairment due to septic shock. To date, initial antibiotic choice is empirical, using a "best guess" of likely organism and sensitivity- an approach adopted due to the lack of rapid identification methods for bacteria. Current culture based methods take up to 5 days to identify the causative bacterial pathogen and its antibiotic sensitivity. This paper provides proof of concept for a biosensor, based on interdigitated electrodes, to detect the presence of S. aureus and ascertain its sensitivity to flucloxacillin rapidly (within 2 hours) in a cost effective manner. The proposed method is label-free and uses non faradic measurements. This is the first study to successfully employ interdigitated electrodes for the rapid detection of antibiotic resistance. The method described has important potential outcomes of faster definitive antibiotic treatment and more rapid clinical response to treatment. PMID- 26811850 TI - Boronic acid recognition based-gold nanoparticle-labeling strategy for the assay of sialic acid expression on cancer cell surface by inductively coupled plasma mass spectrometry. AB - Sialic acids are special sugars widely expressed at the termini of glycan chains on the cell surface, and their expression level on the cancer cell surface is much higher than on the normal cell surface. Herein, we reported an inductively coupled plasma mass spectrometry (ICP-MS) based method with elemental tags for the analysis of sialic acids on the cancer cell surface. The method is based on the selective recognition of sialic acids by biotinylated phenylboronic acid (biotin-APBA) at physiological pH and signal enhancement of gold nanoparticles (AuNPs) in ICP-MS when AuNPs were used as elemental tags labeled on biotin-APBA. A specificity test reveals that the proposed method has high specificity towards cancer cells. Taking HepG2 and MCF-7 cells as two model cancer cells, competitive experiments were performed to estimate the expression level of sialic acids on the cancer cell surface, and it was found that the average numbers of sialic acids expressed on the single MCF-7 and HepG2 cell surface were 7.0 * 10(9) and 5.4 * 10(9), respectively. With sialic acid as the biomarker for cancer cells, the method was further used for cell detection. The limits of detection in terms of cell number for HepG2 and MCF-7 cells were 120 and 64, respectively. And the relative standard deviations for nine replicate determinations of ca. 1000 HepG2 and MCF-7 cells were 9.6% and 8.9%, respectively. The linear ranges for HepG2 cells and MCF-7 cells were 300-10,000 and 170-11,000, respectively. The proposed approach is sensitive as well as selective for the analysis of sialic acids on the cancer cell surface, and is potentially applicable for the study of tumor malignancy and metastasis, which is helpful for biological research and clinical diagnostics. PMID- 26811851 TI - Accurate biometal quantification per individual Caenorhabditis elegans. AB - In the life sciences, small model-organisms are an established research platform. Due to the economy of culturing and maintenance animals such as the roundworm Caenorhabditis elegans, and the fly Drosophila melanogaster, have been instrumental for investigating key genetic pathways, early development, neuronal function, as well as disease pathogenesis and toxicology. Small model organisms have also found utility in the study of inorganic biochemistry, where the role of metal ion cofactors are investigated for numerous fundamental cellular processes. The metabolism and homeostasis of metal ions is also central to many aspects of biology and disease. Accurate quantification of endogenous metal ion content is an important determinant for many biological questions. There is currently no standardised method for quantifying biometal content in individual C. elegans or estimating the variation between individuals within clonal populations. Here, we have determined that ten or more adults are required to quantify physiologically important metals via inductively coupled plasma mass spectrometry (ICP-MS). The accuracy and precision of this method was then compared to synchrotron-based X ray fluorescence microscopy (XFM) to determine the variation between isogenic, developmentally synchronous C. elegans adults. PMID- 26811852 TI - Encapsulation of FRET-based glucose and maltose biosensors to develop functionalized silica nanoparticles. AB - Silicate nanoparticles with immobilized FRET-based biosensors were developed for the detection of glucose and maltose. Immobilization of the protein biosensor in the nanoparticle was achieved through specific interaction between the hexa histidine tag of the protein and a calcium-silicate complex of the silica matrix. Encapsulation of the biosensors preserved the affinity for the respective sugar. Compared to the free biosensors, encapsulation had a stabilizing effect on the biosensor towards chemical and thermal denaturation. The demonstrated immobilization strategy for specific sensing proteins paves the way towards the development of protein-inorganic nanostructures for application in metabolite analyses. PMID- 26811853 TI - Reflections:Neurology and The Humanities. Todd's paralysis. PMID- 26811854 TI - About stroke and pediatric stroke. PMID- 26811855 TI - Author Response. PMID- 26811856 TI - Commentary Author Response. PMID- 26811857 TI - A lesson in empathy. PMID- 26811858 TI - Online PA programs. PMID- 26811859 TI - The Gift of Spirituality. PMID- 26811860 TI - Retraction notice to "KDM3A interacted with p53K372me1 and regulated p53 binding to PUMA in gastric cancer" [Biochem. Biophys. Res. Commun. 467 (2015) 556-561]. PMID- 26811861 TI - Evidence of Negative Cooperativity and Half-Site Reactivity within an F420 Dependent Enzyme: Kinetic Analysis of F420H2:NADP(+) Oxidoreductase. AB - Here, we report the very first example of half-site reactivity and negative cooperativity involving an important F420 cofactor-dependent enzyme. F420H2:NADP(+) oxidoreductase (Fno) is an F420 cofactor-dependent enzyme that catalyzes the reversible reduction of NADP(+) through the transfer of a hydride from the reduced F420 cofactor. These catalytic processes are of major significance in numerous biochemical processes. While the steady-state kinetic analysis showed classic Michaelis-Menten kinetics with varying concentrations of the F420 redox moiety, FO, such plots revealed non-Michaelis-Menten kinetic behavior when NADPH was varied. The double reciprocal plot of the varying concentrations of NADPH displays a downward concave shape, suggesting that negative cooperativity occurs between the two identical monomers. The transient state kinetic data show a burst prior to entering steady-state turnover. The burst suggests that product release is rate-limiting, and the amplitude of the burst phase corresponds to production of product in only one of the active sites of the functional dimer. These results suggest either half-site reactivity or an alternate sites model wherein the reduction of the cofactor, FO occurs at one active site at a time followed by reduction at the second active site. Thus, the data imply that Fno may be a functional regulatory enzyme. PMID- 26811862 TI - First principles thermodynamical modeling of the binodal and spinodal curves in lead chalcogenides. AB - High-throughput ab initio calculations, cluster expansion techniques, and thermodynamic modeling have been synergistically combined to characterize the binodal and the spinodal decompositions features in the pseudo-binary lead chalcogenides PbSe-PbTe, PbS-PbTe, and PbS-PbSe. While our results agree with the available experimental data, our consolute temperatures substantially improve with respect to previous computational modeling. The computed phase diagrams corroborate that in ad hoc synthesis conditions the formation of nanostructure may occur justifying the low thermal conductivities in these alloys. The presented approach, making a rational use of online quantum repositories, can be extended to study thermodynamical and kinetic properties of materials of technological interest. PMID- 26811863 TI - Fastest Effectively Adiabatic Transitions for a Collection of Harmonic Oscillators. AB - We discuss fastest effectively adiabatic transitions (FEATs) for a collection of noninteracting harmonic oscillators with shared controllable real frequencies. The construction of such transitions is presented for given initial and final equilibrium states, and the dependence of the minimum time control on the interval of achievable frequencies is discussed. While the FEAT times and associated FEAT processes are important in their own right as optimal controls, the FEAT time is an added feature which provides a measure of the quality of a shortcut to adiabaticity (STA). The FEAT time is evaluated for a previously reported experiment, wherein a cloud of Rb atoms is cooled following a STA recipe that took about twice as long as the FEAT speed limit, a time efficiency of 50%. PMID- 26811864 TI - The interval testing procedure: A general framework for inference in functional data analysis. AB - We introduce in this work the Interval Testing Procedure (ITP), a novel inferential technique for functional data. The procedure can be used to test different functional hypotheses, e.g., distributional equality between two or more functional populations, equality of mean function of a functional population to a reference. ITP involves three steps: (i) the representation of data on a (possibly high-dimensional) functional basis; (ii) the test of each possible set of consecutive basis coefficients; (iii) the computation of the adjusted p-values associated to each basis component, by means of a new strategy here proposed. We define a new type of error control, the interval-wise control of the family wise error rate, particularly suited for functional data. We show that ITP is provided with such a control. A simulation study comparing ITP with other testing procedures is reported. ITP is then applied to the analysis of hemodynamical features involved with cerebral aneurysm pathology. ITP is implemented in the fdatest R package. PMID- 26811865 TI - Use of a harvested radial artery graft with preservation of the vena comitantes to reduce spasm risk and improve graft patency for extracranial to intracranial bypass: Technical note. AB - BACKGROUND AND SIGNIFICANCE: The vessels of choice for cerebrovascular high-flow direct bypass procedures are the radial artery and the saphenous vein. Radial artery grafts have become favored over saphenous vein grafts because of higher patency rates and better size matching to appropriate recipient vessels. Radial grafts are prone to spasm however, and this may be seen in 4-10% of cases and can be associated with ischemic sequelae. The standard technique for radial artery harvest calls for complete separation of the artery from its adventitial attachments and associated venous network. There is reason to believe that this could contribute to spasm risk and possibly even thrombosis. Radial graft outcomes appear to be improved when the vena comitantes is preserved in cardiac and peripheral applications. We report the novel use of a harvested radial artery graft with preservation of its venae comitantes for extracranial to intracranial bypass. CLINICAL PRESENTATION: The patient is a 59-year-old male who had a blunt head trauma with associated loss of consciousness and who was led to the incidental discovery of a large fusiform middle cerebral artery (MCA) aneurysm. CONCLUSION: Preservation of the vena comitantes when harvesting a radial arterial graft for bypass, along with dual (arterial and venous) anastomoses, and concomitant use of intra-operative vaso-dilatory maneuvers to prevent spasm, may improve overall graft patency and patient outcome. PMID- 26811866 TI - Deep Brain Stimulation of the internal globus pallidus in refractory Tourette Syndrome. AB - OBJECTIVE: Deep Brain Stimulation in psychiatric disorders is becoming an increasingly performed surgery. At present, seven different targets have been stimulated in Tourette Syndrome, including the internal globus pallidus. We describe the effects on tics and comorbid behavioral disorders of Deep Brain Stimulation of the anterior internal globus pallidus in five patients with refractory Tourette Syndrome. METHODS: This study was performed as an open label study with follow-up assessment between 12 and 38 months. Patients were evaluated twice, one month before surgery and at long-term follow-up. Primary outcome was tic severity, assessed by several scales. Secondary outcomes were comorbid behavioral disorders, mood and cognition. The final position of the active contacts of the implanted electrodes was investigated and side effects were reported. RESULTS: Three males and two females were included with a mean age of 41.6 years (SD 9.7). The total post-operative score on the Yale Global Tic Severity Scale was significantly lower than the pre-operative score (42.2+/-4.8 versus 12.8+/-3.8, P=0.043). There was also a significant reduction on the modified Rush Video-Based Tic Rating Scale (13.0+/-2.0 versus 7.0+/-1.6, P=0.041) and in the total number of video-rated tics (259.6+/-107.3 versus 49.6+/-24.8, P=0.043). No significant difference on the secondary outcomes was found, however, there was an improvement on an individual level for obsessive-compulsive behavior. The final position of the active contacts was variable in our sample and no relationship between position and stimulation effects could be established. CONCLUSION: Our study suggests that Deep Brain Stimulation of the anterior internal globus pallidus is effective in reducing tic severity, and possibly also obsessive-compulsive behavior, in refractory Tourette patients without serious adverse events or side-effects. PMID- 26811867 TI - Second surgery for recurrent glioblastoma: A concise overview of the current literature. AB - Optimal treatment for recurrent glioblastoma continues to evolve. Currently, however, there is no consensus in the literature on the role of reoperation in the management of these patients, as several studies provide evidence for a longer overall survival in selected patients with recurrent glioblastoma who underwent second surgery and other studies report a limited impact of second surgery in the clinical course. In this paper, a review of the current literature was performed to analyze the role of reoperation in patients with recurrent glioblastoma and to report the overall survival from diagnosis, progression-free survival and quality of life. Using PubMed and Ovid Medline databases, we performed a review of the literature of the last seven years, finding a total of 28 studies and 2279 patients who underwent second surgery, that were included in the final analysis. The median overall survival from diagnosis and the median survival from second surgery were 18.5 months and 9.7 months, respectively. Extent of resection at reoperation improves overall survival, even in patients with subtotal resection at initial operation. Preoperative performance status and age are important predictors of a longer survival, reason why younger patients with a good preoperative performance status could benefit from reoperation. PMID- 26811869 TI - Molecular dynamics simulation of non-covalent single-walled carbon nanotube functionalization with surfactant peptides. AB - Non-covalent functionalized single-walled carbon nanotubes (SWCNTs) with improved solubility and biocompatibility can successfully transfer drugs, DNA, RNA, and proteins into the target cells. Theoretical studies such as molecular docking and molecular dynamics simulations in fully atomistic scale were used to investigate the hydrophobic and aromatic pi-pi-stacking interaction of designing four novel surfactant peptides for non-covalent functionalization of SWCNTs. The results indicated that the designed peptides have binding affinity towards SWCNT with constant interactions during MD simulation times, and it can even be improved by increasing the number of tryptophan residues. The aromatic content of the peptides plays a significant role in their adsorption in SWCNT wall. The data suggest that pi-pi stacking interaction between the aromatic rings of tryptophan and pi electrons of SWCNTs is more important than hydrophobic effects for dispersing carbon nanotubes; nevertheless SWCNTs are strongly hydrophobic in front of smooth surfaces. The usage of aromatic content of peptides for forming SWCNT/peptide complex was proved successfully, providing new insight into peptide design strategies for future nano-biomedical applications. PMID- 26811870 TI - Contribution of main chain and side chain atoms and their locations to the stability of thermophilic proteins. AB - Proteins belonging to the same class, having similar structures thus performing the same function are known to have different thermal stabilities depending on the source- thermophile or mesophile. The variation in thermo-stability has not been attributed to any unified factor yet and understanding this phenomenon is critically needed in several areas, particularly in protein engineering to design stable variants of the proteins. Toward this motive, the present study focuses on the sequence and structural investigation of a dataset of 373 pairs of proteins; a thermophilic protein and its mesophilic structural analog in each pair, from the perspectives of hydrophobic free energy, hydrogen bonds, physico-chemical properties of amino acids and residue-residue contacts. Our results showed that the hydrophobic free energy due to carbon, charged nitrogen and charged oxygen atoms was stronger in 65% of thermophilic proteins. The number of hydrogen bonds which bridges the buried and exposed regions of proteins was also greater in case of thermophiles. Amino acids of extended shape, volume and molecular weight along with more medium and long range contacts were observed in many of the thermophilic proteins. These results highlight the preference of thermophiles toward the amino acids with larger side chain and charged to make up greater free energy, better packing of residues and increase the overall compactness. PMID- 26811868 TI - Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children. AB - Early-life antibiotic use is associated with increased risk for metabolic and immunological diseases, and mouse studies indicate a causal role of the disrupted microbiome. However, little is known about the impacts of antibiotics on the developing microbiome of children. Here we use phylogenetics, metagenomics and individual antibiotic purchase records to show that macrolide use in 2-7 year-old Finnish children (N=142; sampled at two time points) is associated with a long lasting shift in microbiota composition and metabolism. The shift includes depletion of Actinobacteria, increase in Bacteroidetes and Proteobacteria, decrease in bile-salt hydrolase and increase in macrolide resistance. Furthermore, macrolide use in early life is associated with increased risk of asthma and predisposes to antibiotic-associated weight gain. Overweight and asthmatic children have distinct microbiota compositions. Penicillins leave a weaker mark on the microbiota than macrolides. Our results support the idea that, without compromising clinical practice, the impact on the intestinal microbiota should be considered when prescribing antibiotics. PMID- 26811872 TI - Effectiveness of Meningococcal B Vaccine against Endemic Hypervirulent Neisseria meningitidis W Strain, England. AB - Serum samples from children immunized with a meningococcal serogroup B vaccine demonstrated potent serum bactericidal antibody activity against the hypervirulent Neisseria meningitidis serogroup W strain circulating in England. The recent introduction of this vaccine into the United Kingdom national immunization program should also help protect infants against this endemic strain. PMID- 26811871 TI - Crystal morphology prediction of 1,3,3-trinitroazetidine in ethanol solvent by molecular dynamics simulation. AB - In order to understand the mechanism of the effect of solvent on the crystal morphology of explosives, and be convenient for the choice of crystallization solvent, the attachment energy (AE) model was performed to predict the growth morphology and the main crystal faces of 1,3,3-trinitroazetidine (TNAZ) in vacuum. The molecular dynamics simulation was applied to investigate the interactions of TNAZ crystal faces and ethanol solvent, and the growth habit of TNAZ in ethanol solvent was predicted using the modified AE model. The results indicate that the morphology of TNAZ crystal in vacuum is dominated by the six faces of [021], [112], [002], [102], [111] and [020], and the crystal shape is similar to polyhedron. In ethanol solvent, The binding strength of ethanol with TNAZ faces changes in the order of [021]>[112]>[002]>[102]>[111]>[020], which causes that [111] and [020] faces disappear and the crystal morphology becomes more regular. The radial distribution function analysis shows that the interactions between solvent and crystal faces mainly consist of coulomb interaction, van der Waals force and hydrogen bonds. PMID- 26811873 TI - Modulation of the cellular content of metabolites in adipocytes by insulin. AB - Although the insulin-mediated cell signaling pathway has been extensively examined, changes in the cellular content of metabolites currently remain unclear. We herein examined metabolite contents in 3T3-L1 adipocytes treated with insulin using a metabolomic analysis. Fifty-four compounds were detected, and the contents of metabolites from the citric acid cycle increased in response to the insulin treatment for 4 h, which was sensitive to U0126 and LY294002, inhibitors for mitogen-activated protein kinase kinase-1 and phosphoinositide 3-kinase, respectively. The cellular contents of fumaric acid and malic acid were increased more by insulin than those of citric acid and succinic acid. Time-course changes in metabolites from the citric acid cycle exhibited oscillations with a 2-h cycle. A metabolic pathway analysis also indicated that insulin affected the metabolism of alanine, aspartate and glutamate, as well as that of arginine and proline. The contents of free amino acids were slightly decreased by the insulin treatment, while the co-treatment with U0126 and LY294002 abrogated these insulin mediated decreases. The present study revealed the unexpected accumulation of citric acid cycle metabolites in adipocytes by insulin. Our results indicate the usefulness of metabolomic analyses for obtaining a more comprehensive understanding of the regulation of metabolic pathways in cell-culture systems. PMID- 26811874 TI - Direct Observation of an Oxepin from a Bacterial Cytochrome P450-Catalyzed Oxidation. AB - The cytochromes P450 are hemoproteins that catalyze a range of oxidative C-H functionalization reactions, including aliphatic and aromatic hydroxylation. These transformations are important in a range of biological contexts, including biosynthesis and xenobiotic biodegradation. Much work has been carried out on the mechanism of aliphatic hydroxylation, implicating hydrogen atom abstraction, but aromatic hydroxylation is postulated to proceed differently. One mechanism invokes as the key intermediate an arene oxide (and/or its oxepin tautomer). Conclusive isolation of this intermediate has remained elusive and, currently, direct formation of phenols from a Meisenheimer intermediate is believed to be favored. We report here the identification of a P450 [P450cam (CYP101A1) and P450cin (CYP176A1)]-generated arene oxide as a product of in vitro oxidation of tert-butylbenzene. Computations (CBS-QB3) predict that the arene oxide and oxepin have similar stabilities to other arene oxides/oxepins implicated (but not detected) in P450-mediated transformations, suggesting that arene oxides can be unstable terminal products of P450-catalyzed aromatic oxidation that can explain the origin of some observed metabolites. PMID- 26811876 TI - Size-Dependent Exciton Formation Dynamics in Colloidal Silicon Quantum Dots. AB - We report size-dependent exciton formation dynamics within colloidal silicon quantum dots (Si QDs) using time-resolved terahertz (THz) spectroscopy measurements. THz photoconductivity measurements are used to distinguish the initially created hot carriers from excitons that form at later times. At early pump/probe delays, the exciton formation dynamics are revealed by the temporal evolution of the THz transmission. We find an increase in the exciton formation time, from ~500 to ~900 fs, as the Si QD diameter is reduced from 7.3 to 3.4 nm and all sizes exhibit slower hot-carrier relaxation times compared to bulk Si. In addition, we determine the THz absorption cross section at early delay times is proportional to the carrier mobility while at later delays is proportional to the exciton polarizability, alphaX. We extract a size-dependent alphaX and find an ~r(4) dependence, consistent with previous reports for quantum-confined excitons in CdSe, InAs, and PbSe QDs. The observed slowing in exciton formation time for smaller Si QDs is attributed to decreased electron-phonon coupling due to increased quantum confinement. These results experimentally verify the modification of hot-carrier relaxation rates by quantum confinement in Si QDs, which likely plays a significant role in the high carrier multiplication efficiency observed in these nanomaterials. PMID- 26811875 TI - Anaplasmataceae-Specific PCR for Diagnosis and Therapeutic Guidance for Symptomatic Neoehrlichiosis in Immunocompetent Host. AB - Candidatus Neoehrlichia is increasingly being recognized worldwide as a tickborne pathogen. We report a case of symptomatic neoehrlichiosis in an immunocompetent Austria resident who had recently returned from travel in Tanzania. The use of Anaplasmataceae-specific PCR to determine the duration of antimicrobial therapy seems reasonable to avert recrudescence. PMID- 26811877 TI - A phylotranscriptomic analysis of gene family expansion and evolution in the largest order of pleurocarpous mosses (Hypnales, Bryophyta). AB - The pleurocarpous mosses (i.e., Hypnanae) are a species-rich group of land plants comprising about 6,000 species that share the development of female sex organs on short lateral branches, a derived trait within mosses. Many of the families within Hypnales, the largest order of pleurocarpous mosses, trace their origin to a rapid radiation less than 100 million years ago, just after the rise of the angiosperms. As a result, the phylogenetic resolution among families of Hypnales, necessary to test evolutionary hypotheses, has proven difficult using one or few loci. We present the first phylogenetic inference from high-throughput sequence data (transcriptome sequences) for pleurocarpous mosses. To test hypotheses of gene family evolution, we built a species tree of 21 pleurocarpous and six acrocarpous mosses using over one million sites from 659 orthologous genes. We used the species tree to investigate the genomic consequences of the shift to pleurocarpy and to identify whether patterns common to other plant radiations (gene family expansion, whole genome duplication, or changes in the molecular signatures of selection) could be observed. We found that roughly six percent of all gene families have expanded in the pleurocarpous mosses, relative to acrocarpous mosses. These gene families are enriched for several gene ontology (GO) terms, including interaction with other organisms. The increase in copy number coincident with the radiation of Hypnales suggests that a process such as whole genome duplication or a burst of small-scale duplications occurred during the diversification. In over 500 gene families we found evidence of a reduction in purifying selection. These gene families are enriched for several terms in the GO hierarchy related to "tRNA metabolic process." Our results reveal candidate genes and pathways that may be associated with the transition to pleurocarpy, illustrating the utility of phylotranscriptomics for the study of molecular evolution in non-model species. PMID- 26811879 TI - Capturing metal-support interactions in situ during the reduction of a Re promoted Co/gamma-Al2O3 catalyst. AB - The reduction of a Re promoted Co/gamma-Al2O3 catalyst was monitored in situ by synchrotron X-ray powder diffraction (XRPD) under H2 environment. Whole powder pattern analysis revealed a non-linear expansion of the unit cell of gamma-Al2O3 during the reduction process, suggesting the diffusion of Co cations into the structure of the support. The non-linear cell expansion coincided with the formation of a CoO phase. In addition, space resolved diffraction at the inlet and the outlet of the reactor evidenced a negative effect of the partial pressure of indigenous H2O(g) on the reduction process. PMID- 26811880 TI - Suppression of Hepatic Inflammation via Systemic siRNA Delivery by Membrane Disruptive and Endosomolytic Helical Polypeptide Hybrid Nanoparticles. AB - Treatment of inflammatory diseases represents one of the biggest clinical challenges. RNA interference (RNAi) against TNF-alpha provides a promising modality toward anti-inflammation therapy, but its therapeutic potential is greatly hampered by the by the lack of efficient siRNA delivery vehicles in vivo. Herein, we report a hybrid nanoparticulate (HNP) system based on a cationic helical polypeptide PPABLG for the efficient delivery of TNF-alpha siRNA. The helical structure of PPABLG features pore formation on cellular and endosomal membranes to facilitate the direct translocation as well as endosomal escape of TNF-alpha siRNA in macrophages, representing a unique superiority to a majority of the existing polycation-based gene vectors that experience severe endosomal entrapment and lysosomal degradation. As such, HNPs containing TNF-alpha siRNA afforded effective systemic TNF-alpha knockdown following systemic administration at a low dose of 50 MUg of siRNA/kg and thus demonstrated a potent anti inflammatory effect to rescue animals from LPS/d-GalN-induced hepatic sepsis. This study therefore verifies that the bioactive secondary structure of polypeptides significantly dominates the in vivo siRNA delivery efficiency, and the unique properties of PPABLG HNPs render remarkable potentials for anti inflammation therapies. PMID- 26811881 TI - Simultaneous activation of Nrf2 and elevation of antioxidant compounds for reducing oxidative stress and chronic inflammation in human Alzheimer's disease. AB - Despite extensive research, neither the incidence nor the rate of progression of Alzheimer's disease (AD) has significantly changed. Some biochemical and genetic defects that initiate and promote AD include: (a) increased oxidative stress, (b) chronic inflammation (c) mitochondrial dysfunction, (d) Abeta1-42 peptides generated from the amyloid precursor protein (APP), (e) proteasome inhibition, and (f) mutations in APP, presenilin-1 and presenilin-2 genes. Increased oxidative stress appears to precede other biochemical and genetic defects. Oxidative damage induces chronic inflammation. Therefore, reducing these defects simultaneously may reduce the development and progression of AD. Previous studies with individual antioxidants produced consistent benefits in animal models of AD; however, a similar approach produced inconsistent results in human AD. This review proposes a hypothesis that simultaneous elevation of the levels of antioxidant enzymes and antioxidant compounds is necessary for optimally reducing oxidative stress and chronic inflammation in human AD. Supplementation can enhance the levels of antioxidant compounds; but elevation of antioxidant enzymes requires activation of Nrf2. This review discusses activation and regulation of Nrf2. The need for multi- antioxidants that can affect multi-targets has been proposed without specific recommendations. This review proposes a micronutrient mixture that would simultaneously enhance the levels of antioxidant enzymes and antioxidant compounds in human AD. PMID- 26811882 TI - Adsorption Studies of Organophosphonic Acids on Differently Activated Gold Surfaces. AB - In this study, the formation of self-assembled monolayers consisting of three organophosphonic acids (vinyl-, octyl-, and tetradecylphosphonic acid) from isopropanol solutions onto differently activated gold surfaces is studied in situ and in real time using multiparameter surface plasmon resonance (MP-SPR). Data retrieved from MP-SPR measurements revealed similar adsorption kinetics for all investigated organophosphonic acids (PA). The layer thickness of the immobilized PA is in the range of 0.6-1.8 nm corresponding to monolayer-like coverage and correlates with the length of the hydrocarbon chain of the PA molecules. After sintering the surfaces, the PA are irreversibly attached onto the surfaces as proven by X-ray photoelectron spectroscopy and attenuated total reflection infrared and grazing incidence infrared spectroscopy. Potential adsorption modes and interaction mechanisms are proposed. PMID- 26811883 TI - Posterior Segment Drug Delivery Devices: Current and Novel Therapies in Development. AB - Ocular drug delivery by conventional routes of administration does not maintain therapeutic drug concentrations in the target tissues for a long duration because of various anatomical and physiological barriers. Treatment of diseases of the posterior segment of the eye requires novel drug delivery systems that can overcome these barriers for efficacious delivery, provide controlled release for the treatment of chronic diseases, and increase patient's and doctor's convenience to reduce the dosing frequency and associated side effects. Thereby, an increasing number of sustained-release drug delivery devices using different mechanisms have been developed. This article discusses various current and future sustained-release drug delivery systems for the posterior segment disorders. PMID- 26811884 TI - Eyespots. AB - Skelhorn et al. introduce eyespots the circular markings resembling vertebrate eyes found on many animals. PMID- 26811885 TI - COP-coated vesicles. AB - Approximately one third of a cell's proteins are destined to function outside the cell's boundaries or while embedded within cellular membranes. Ensuring these proteins reach their diverse final destinations with temporal and spatial accuracy is essential for cellular physiology. In eukaryotes, a set of interconnected organelles form the secretory pathway, which encompasses the terrain that these proteins must navigate on their journey from their site of synthesis on the ribosome to their final destinations. Traffic of proteins within the secretory pathway is directed by cargo-bearing vesicles that transport proteins from one compartment to another. Key steps in vesicle-mediated trafficking include recruitment of specific cargo proteins, which must collect locally where a vesicle forms, and release of an appropriate cargo-containing vessel from the donor organelle (Figure 1). The newly formed vesicle can passively diffuse across the cytoplasm, or can catch a ride on the cytoskeleton to travel directionally. Once the vesicle arrives at its precise destination, the membrane of the carrier merges with the destination membrane to deliver its cargo. PMID- 26811886 TI - The fast and forceful kicking strike of the secretary bird. AB - The study of animal locomotion has uncovered principles that can be applied to bio-inspired robotics, prosthetics and rehabilitation medicine, while also providing insight into musculoskeletal form and function [1-4]. In particular, study of extreme behaviors can reveal mechanical constraints and trade-offs that have influenced evolution of limb form and function [1,2]. Secretary birds (Sagittarius serpentarius; Figure 1A) are large terrestrial birds of prey endemic to sub-Saharan Africa, which feed on snakes, lizards and small mammals [5]. They frequently kick and stamp on the prey's head until it is killed or incapacitated, particularly when dispatching larger lizards and venomous snakes [5]. The consequences of a missed strike when hunting venomous snakes can be deadly [5], so the kicking strikes of secretary birds require fast yet accurate neural control. Delivery of fast, forceful and accurate foot strikes that are sufficient to stun and kill prey requires precision targeting, demanding a high level of coordination between the visual and neuromuscular systems. PMID- 26811887 TI - Primate Thalamus: More Than Meets an Eye. AB - A recent study shows conclusively that the koniocellular layers of the marmoset dorsal lateral geniculate nucleus have binocularly responsive neurons. This adds a new twist to the traditional view about binocular processing in the primate visual system and raises questions about the role of dorsal lateral geniculate nucleus in early binocular processing. PMID- 26811888 TI - Gene Regulation: Stable Noise. AB - Transcriptional regulation is noisy, yet despite this variability, embryonic development reproducibly generates form and function. Recent work demonstrates that patterns of transcriptional activity in embryos are stably inherited through mitosis. These observations have implications for how accuracy arises in development. PMID- 26811889 TI - Systems Neuroscience: How the Cortex Contributes to Skilled Movements. AB - A recent study demonstrates how acute neural circuit manipulations can lead to overestimations of circuit function, while chronic manipulations can reveal compensatory modes of plasticity that restore behavior. PMID- 26811890 TI - Evolution: Welcome to Symbiont Prison. AB - Can egalitarian partnerships exist in nature? A new study demonstrates how protist hosts use and abuse their algal symbionts depending on their needs. While this relationship allows protists to survive in low nutrient conditions, it leaves little room for algal retaliation. PMID- 26811891 TI - Plant Biology: Seedling Emergence through Soil. AB - The resistance encountered by a seedling as it pushes through the soil causes inhibition of stem elongation and stimulates stem thickening, facilitating soil penetration. A new study demonstrates that two proteolytic pathways work in double-negative fashion - one targeting the other - to protect transcription factors central to this response. PMID- 26811892 TI - Visual Plasticity: Blindsight Bridges Anatomy and Function in the Visual System. AB - Some people who are blind due to damage to their primary visual cortex, V1, can discriminate stimuli presented within their blind visual field. This residual function has been recently linked to a pathway that bypasses V1, and connects the thalamic lateral geniculate nucleus directly with the extrastriate cortical area MT. PMID- 26811893 TI - Balancing Selection: Walking a Tightrope. AB - Combining modern transgenic techniques with fitness measurements and enzyme activity assays, a new study demonstrates a habitat-dependent tradeoff between two alleles of a key detoxification enzyme in fruit flies. The elegant findings provide concrete, elusive evidence supporting a foundational and controversial theory about the maintenance of genetic variation. PMID- 26811894 TI - Animal Behaviour: Friendship Enhances Trust in Chimpanzees. AB - Individuals that participate in exchanges with delayed rewards can be exploited if their partners don't reciprocate. In humans, friendships are built on trust, and trust enhances cooperation. New evidence suggests that close social bonds also enhance trust in chimpanzees. PMID- 26811895 TI - Signal Evolution: 'Shaky' Evidence for Sensory Bias. AB - A study of tropical crickets suggests that a twitchy response to ultrasonic bat calls has been co-opted for mate location. The neuroethological approach picks apart some surprising evolutionary steps that could inform the widespread occurrence of complex duetting behaviour. PMID- 26811896 TI - Microbiology: Social Suicide for a Good Cause. AB - Extracellular DNA is an important component of the biofilm matrix. Now, Pseudomonas aeruginosa is shown to control autolysis through the production of HQNO, a quorum-sensing-regulated respiratory poison. Thus, HQNO-driven autolysis links programmed cell death with quorum sensing and biofilm formation. PMID- 26811898 TI - Reactions of arynes promoted by silver ions. AB - Arynes are unique aromatic species that display versatile reactivity in a variety of transformations. It has been demonstrated that the reaction profiles of arynes can be altered by transition metal additives, and one of the earliest examples of the metal additive effect was observed with silver ions (Ag(+)). Especially, in the presence of Ag(+), benzyne showed distinctive reactivity and selectivity toward pi-nucleophiles compared to the corresponding reaction in its absence. Although more experimental data need to be accumulated to accurately define the Ag(+) additive effect, based on its role displayed in various transformations, we can infer that Ag(+) interacts with arynes to form a reactive intermediate, which behaves like a silver-bound aryl cation or 1,2-carbene-silver carbenoid. In this tutorial review, various aryne-mediated reactions involving Ag(+) or other organosilver species are discussed, which show a bird's-eye view on the Ag(+) effect in aryne chemistry such that further explorations of the unique reactivity of arynes under the influence Ag(+) will be inspired. PMID- 26811899 TI - Pressure-induced changes in structural and dynamic properties of liquid Fe close to the melting line. An ab initio study. AB - The static and dynamic properties of liquid Fe at high pressure and temperature have been studied using an ab initio molecular dynamics method. We have focused on four thermodynamic states at pressures of 27, 42, 50 and 58 GPa for which x ray scattering data are available. The calculated static structure shows very good agreement with the available experimental data, including an asymmetric second peak which becomes more marked with increasing pressure. The dynamical structure reveals the existence of propagating density fluctuations and the associated dispersion relation has also been determined. The relaxation mechanisms for the density fluctuations have been analyzed in terms of a model with two decay channels (fast and slow, respectively). We found that the thermal relaxation proceeds along the slow decaying channel whereas the fast one is that of the viscoelastic relaxation. The possible coupling between longitudinal and transverse excitation modes has been investigated by looking at specific signatures in two wavevector regions: the first one is located around the position of the main peak of the structure factor, qp, as suggested by the recently reported appearance of high frequency transverse waves in liquid Li under high pressures; the second region is around qp/2, as suggested by the recent finding of transverse acoustic modes in inelastic x-ray scattering intensities of liquid Fe at ambient pressure. Finally, results are also reported for several transport coefficients. PMID- 26811897 TI - A Multi-Country Cross-Sectional Study of Vaginal Carriage of Group B Streptococci (GBS) and Escherichia coli in Resource-Poor Settings: Prevalences and Risk Factors. AB - BACKGROUND: One million neonates die each year in low- and middle-income countries because of neonatal sepsis; group B Streptococcus (GBS) and Escherichia coli are the leading causes. In sub-Saharan Africa, epidemiological data on vaginal GBS and E. coli carriage, a prerequisite for GBS and E. coli neonatal sepsis, respectively, are scarce but necessary to design and implement prevention strategies. Therefore, we assessed vaginal GBS and E. coli carriage rates and risk factors and the GBS serotype distribution in three sub-Saharan countries. METHODS: A total of 430 women from Kenya, Rwanda and South Africa were studied cross-sectionally. Vaginal carriage of GBS and E. coli, and GBS serotype were assessed using molecular techniques. Risk factors for carriage were identified using multivariable logistic regression analysis. RESULTS: Vaginal carriage rates in reference groups from Kenya and South Africa were 20.2% (95% CI, 13.7-28.7%) and 23.1% (95% CI, 16.2-31.9%), respectively for GBS; and 25.0% (95% CI, 17.8 33.9%) and 27.1% (95% CI, 19.6-36.2%), respectively for E. coli. GBS serotypes Ia (36.8%), V (26.3%) and III (14.0%) were most prevalent. Factors independently associated with GBS and E. coli carriage were Candida albicans, an intermediate vaginal microbiome, bacterial vaginosis, recent vaginal intercourse, vaginal washing, cervical ectopy and working as a sex worker. GBS and E. coli carriage were positively associated. CONCLUSIONS: Reduced vaginal GBS carriage rates might be accomplished by advocating behavioral changes such as abstinence from sexual intercourse and by avoidance of vaginal washing during late pregnancy. It might be advisable to explore the inclusion of vaginal carriage of C. albicans, GBS, E. coli and of the presence of cervical ectopy in a risk- and/or screening-based administration of antibiotic prophylaxis. Current phase II GBS vaccines (a trivalent vaccine targeting serotypes Ia, Ib, and III, and a conjugate vaccine targeting serotype III) would not protect the majority of women against carriage in our study population. PMID- 26811901 TI - Cardiac Effects of Attenuating Gsalpha - Dependent Signaling. AB - AIMS: Inhibition of beta-adrenergic signalling plays a key role in treatment of heart failure. Gsalpha is essential for beta-adrenergic signal transduction. In order to reduce side-effects of beta-adrenergic inhibition diminishing beta adrenergic signalling in the heart at the level of Gsalpha is a promising option. METHODS AND RESULTS: We analyzed the influence of Gsalpha on regulation of myocardial function and development of cardiac hypertrophy, using a transgenic mouse model (C57BL6/J mice) overexpressing a dominant negative Gsalpha-mutant under control of the alpha-MHC-promotor. Cardiac phenotype was characterized in vivo and in vitro and under acute and chronic beta-adrenergic stimulation. At rest, Gsalpha-DN-mice showed bradycardia (602 +/- 13 vs. 660 +/- 17 bpm, p<0.05) and decreased dp/dtmax (5037 +/- 546- vs. 6835 +/- 505 mmHg/s, p = 0.02). No significant differences were found regarding ejection fraction, heart weight and cardiomyocyte size. beta-blockade by propranolol revealed no baseline differences of hemodynamic parameters between wildtype and Gsalpha-DN-mice. Acute adrenergic stimulation resulted in decreased beta-adrenergic responsiveness in Gsalpha-DN mice. Under chronic adrenergic stimulation, wildtype mice developed myocardial hypertrophy associated with increase of LV/BW-ratio by 23% (4.4 +/- 0.2 vs. 3.5 +/- 0.1 mg/g, p<0.01) and cardiac myocyte size by 24% (14927 +/- 442 px vs. 12013 +/- 583 px, p<0.001). In contrast, both parameters were unchanged in Gsalpha-DN mice after chronic isoproterenol stimulation. CONCLUSION: Overexpression of a dominant negative mutant of Gsalpha leads to decreased beta-adrenergic responsiveness and is protective against isoproterenol-induced hypertrophy. Thus, Gsalpha-DN-mice provide novel insights into beta-adrenergic signal transduction and its modulation in myocardial overload and failure. PMID- 26811900 TI - Repeated Activation of Lung Invariant NKT Cells Results in Chronic Obstructive Pulmonary Disease-Like Symptoms. AB - Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation, mucus hypersecretion, and emphysema, which lead to reduced lung function and breathlessness. The pathologies of COPD are due to an abnormal immune response. Invariant natural killer T (iNKT) cells are an important population of innate lymphocytes and have been implicated in the regulation of immune responses associated with a broad range of diseases including COPD. We have here analyzed the role of iNKT cells in a model of COPD induced by repeated intranasal administration of iNKT cell agonist alpha-galactosylceramide (alpha GalCer). Our results demonstrated that mice that received repeated intranasal administration of alpha-GalCer had molecular and inflammatory features of COPD including airway inflammation with significant increases in infiltration of macrophages and lymphocytes, CD8+ T cells, as well as proinflammatory cytokines IL-6 and TNF-alpha. In particular, these mice also showed the presence of pulmonary emphysema, mucus production, and pulmonary fibrosis. Furthermore, neutralization of IL-4 reduced alpha-GalCer induced emphysema. This study indicates the importance of iNKT cells in the pathogenesis of COPD by an IL-4 dependent mechanism. PMID- 26811902 TI - Comparative analysis of virus-derived small RNAs within cassava (Manihot esculenta Crantz) infected with cassava brown streak viruses. AB - Infection of plant cells by viral pathogens triggers RNA silencing, an innate antiviral defense mechanism. In response to infection, small RNAs (sRNAs) are produced that associate with Argonaute (AGO)-containing silencing complexes which act to inactivate viral genomes by posttranscriptional gene silencing (PTGS). Deep sequencing was used to compare virus-derived small RNAs (vsRNAs) in cassava genotypes NASE 3, TME 204 and 60444 infected with the positive sense single stranded RNA (+ssRNA) viruses cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV), the causal agents of cassava brown streak disease (CBSD). An abundance of 21-24nt vsRNAs was detected and mapped, covering the entire CBSV and UCBSV genomes. The 21nt vsRNAs were most predominant, followed by the 22 nt class with a slight bias toward sense compared to antisense polarity, and a bias for adenine and uracil bases present at the 5'-terminus. Distribution and frequency of vsRNAs differed between cassava genotypes and viral genomes. In susceptible genotypes TME 204 and 60444, CBSV-derived sRNAs were seen in greater abundance than UCBSV-derived sRNAs. NASE 3, known to be resistant to UCBSV, accumulated negligible UCBSV-derived sRNAs but high populations of CBSV derived sRNAs. Transcript levels of cassava homologues of AGO2, DCL2 and DCL4, which are central to the gene-silencing complex, were found to be differentially regulated in CBSV- and UCBSV-infected plants across genotypes, suggesting these proteins play a role in antiviral defense. Irrespective of genotype or viral pathogen, maximum populations of vsRNAs mapped to the cytoplasmic inclusion, P1 and P3 protein-encoding regions. Our results indicate disparity between CBSV and UCBSV host-virus interaction mechanisms, and provide insight into the role of virus-induced gene silencing as a mechanism of resistance to CBSD. PMID- 26811903 TI - Avian leukosis virus subgroup J triggers caspase-1-mediated inflammatory response in chick livers. AB - Many pathogens trigger caspase-1-mediated innate immune responses. Avian leukosis virus subgroup J (ALV-J) causes serious immunosuppression and diverse tumors in chicks. The caspase-1 inflammasome mechanism of response to ALV-J invading remains unclear. Here we investigated the expression of caspase-1, the inflammasome adaptor NLRP3, IL-1beta and IL-18 in response to ALV-J infection in the liver of chick. We found caspase-1 mRNA expression was elevated at 5 dpi and peaked at 7 dpi in ALV-J infected animals. Corresponding to this, the expressions of NLRP3 and proinflammatory cytokines IL-1beta and IL-18 were significantly increased at 5 or 7 dpi. In addition, caspase-1 protein expression and inflammatory cell infiltration were induced after virus infection. These results indicated that ALV-J infection could trigger the caspase-1- mediated inflammatory response in chicks. Thus, an understanding of the inflammatory responses can provide a better insight into the pathogenicity of ALV-J and a possible anti virus target for ALV-J infection. PMID- 26811904 TI - Gene silencing of VP9 gene impairs WSSV infectivity on Macrobrachium rosenbergii. AB - White Spot Syndrome Virus (WSSV) remains the most widespread and devastating infectious agent that hit the shrimp aquaculture industry worldwide. To date, there are no known effective strategies yet to combat WSSV infection. Hence, functional studies on genes critical for viral infection is essential in elucidating shrimp-virus interaction. Here we report the function of a gene from WSSV coding for a non-structural protein, VP9, utilizing RNA interference. Silencing of VP9 gene also effectively suppressed other gene region in the WSSV genome (wsv168 gene) as early as day 1 post infection (dpi). Three set-ups using Macrobrachium rosenbergii shrimp were prepared for treatment using VP9-dsRNA, GFP dsRNA, and PBS. Each shrimp was challenge with WSSV, and survival rate was recorded. VP9- and GFP-dsRNA injected shrimps showed a significant survival rate of 80% and 70%, respectively, in contrast to 0% of the PBS injected shrimps at 25dpi. Re-infection of shrimp survivors using a higher viral titer concentration, concurrent with the infection of new shrimp samples for the PBS control group, resulted in a significant 67% survival rate for VP9-dsRNA compared to 0% with that of GFP-dsRNA and PBS group. Challenge test on two more species, Penaeus monodon and Marsupenaeus japonicus, also significantly increased survival after VP9-dsRNA treatment. Our results provided evidence that VP9 gene plays an essential role in WSSV replication and it can be a potent target gene in the development of RNAi therapeutics for shrimps. PMID- 26811905 TI - Two second-site mutations compensate the engineered mutation of R7A in vesicular stomatitis virus nucleocapsid protein. AB - The functional template for the transcription and replication of vesicular stomatitis virus (VSV) is genomic RNA encapsidated by nucleocapsid (N) protein. Previous studies showed that the amino acid R7 in the N-terminal arm of N is involved in N-N interaction in the N-RNA complex. In our study, the recombinant virus with mutation of R7A (rVSV(R7A)) in N was recovered, and the replication level of passage 1 (P1) of rVSV(R7A) was 1000 times lower than that of wild-type rVSV at 37 degrees C. After eight passages, the replication level of P8 of rVSV(R7A) with two second-site mutations in the genome (T242 P in N protein and U7-U8 in G-L gene junction) was significantly higher than that of P1. Furthermore, we demonstrate that the mutation of either T242P or U7-U8 can compensate the effect caused by the mutation of R7A on the replication of rVSV(R7A). Therefore, we conclude that two second-site mutations both can compensated the engineered mutation of R7A in VSV N protein. PMID- 26811906 TI - Mercury induced haemocyte alterations in the terrestrial snail Cantareus apertus as novel biomarker. AB - The aim of the present work was to study the response of a suite of cellular and biochemical markers in the terrestrial snail Cantareus apertus exposed to mercury in view of future use as sensitive tool suitable for mercury polluted soil monitoring and assessment. Besides standardized biomarkers (metallothionein, acetylcholinesterase, and lysosomal membrane stability) novel cellular biomarkers on haemolymph cells were analyzed, including changes in the spread cells/round cells ratio and haemocyte morphometric alterations. The animals were exposed for 14 days to Lactuca sativa soaked for 1h in HgCl2 solutions (0.5 e 1 MUM). The temporal dynamics of the responses were assessed by measurements at 3, 7 and 14 days. Following exposure to HgCl2 a significant alteration in the relative frequencies of round cells and spread cells was evident, with a time and dose dependent increase of the frequencies of round cells with respect to spread cells. These changes were accompanied by cellular morphometric alterations. Concomitantly, a high correspondence between these cellular responses and metallothionein tissutal concentration, lysosomal membrane stability and inhibition of AChE was evident. The study highlights the usefulness of the terrestrial snail C. apertus as bioindicator organism for mercury pollution biomonitoring and, in particular, the use of haemocyte alterations as a suitable biomarker of pollutant effect to be included in a multibiomarker strategy. PMID- 26811907 TI - Effects of nonylphenol on key hormonal balances and histopathology of the endangered Caspian brown trout (Salmo trutta caspius). AB - Endocrine disruptor chemicals (EDCs) potentially pose a hazard to endangered species. Evaluation of the sensitivity of these species to EDCs could be helpful for protecting their populations. So, the present study investigated the adverse effects of nonylphenol, an EDC, on the endocrine hormones and histopathology of male and female juvenile Caspian brown trout (Salmo trutta caspius) following 21 days of exposure to nominal concentrations of 1, 10 and 100 MUg/l. The results showed that the HSI and plasma total calcium of male and female fishes exposed to 100 MUg/l nonylphenol were significantly increased compared with the control groups (P<0.001). The male plasma T3 level was significantly decreased in 10 (P<0.01) and 100 (P<0.001) MUg/l nonylphenol. The female T3 level increased in 1 MUg/l nonylphenol concentration (P<0.05). The plasma T4 of males showed significant elevation in fishes exposed to 100 MUg/l nonylphenol (P<0.05), but no change for females in any of treatment groups relative to controls (P>0.05). No significant effect of nonylphenol exposure was observed on male plasma TSH levels (P>0.05), whereas, in females, nonylphenol at all concentrations significantly reduced TSH levels. A bell-shaped response was observed in male and female plasma GH levels. Moreover, various histopathological lesions were observed in gill and intestine tissues of fishes exposed to different nonylphenol concentrations. These results demonstrate the high sensitivity of this endangered species to even environmentally relevant concentrations of nonylphenol. Furthermore, Caspian brown trout could be used as bioindicators reflecting the toxicity of nonylphenol. PMID- 26811908 TI - Ammonia toxicity induces glutamine accumulation, oxidative stress and immunosuppression in juvenile yellow catfish Pelteobagrus fulvidraco. AB - A study was carried to test the response of yellow catfish for 28 days under two ammonia concentrations. Weight gain of fish exposure to high and low ammonia abruptly increased at day 3. There were no significant changes in fish physiological indexes and immune responses at different times during 28-day exposure to low ammonia. Fish physiological indexes and immune responses in the treatment of high ammonia were lower than those of fish in the treatment of low ammonia. When fish were exposed to high ammonia, the ammonia concentration in the brain increased by 19-fold on day 1. By comparison, liver ammonia concentration reached its highest level much earlier at hour 12. In spite of a significant increase in brain and liver glutamine concentration, there was no significant change in glutamate level throughout the 28-day period. The total superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione reductase (GR) activities in the brain gradually decreased from hour 0 to day 28. Liver SOD, GPX and GR activities reached the highest levels at hour 12, and then gradually decreased. Thiobarbituric acid reactive substance brain and liver content gradually increased throughout the 28-day period. Lysozyme, acid phosphatase and alkaline phosphatase activities in the liver reached exceptionally low levels after day 14. This study indicated that glutamine accumulation in the brain was not the major cause of ammonia poisoning, the toxic reactive oxygen species is not fully counter acted by the antioxidant enzymes and immunosuppression is a process of gradual accumulation of immunosuppressive factors. PMID- 26811910 TI - Plasma concentrations of amino acid and nicotinamide metabolites in rheumatoid arthritis--potential biomarkers of disease activity and drug treatment. AB - This study aimed to evaluate changes in plasma amino acid and nicotinamide metabolites concentrations in rheumatoid arthritis (RA) in a search for potential biomarkers of the disease activity and the effect treatment. Analysis of plasma metabolite patterns with liquid chromatography/mass spectrometry revealed specific changes in RA as well as correlations with clinical parameters. Combined concentration parameter calculated as [aspartic acid] + [threonine] + [tryptophan] - [histidine] - [phenylalanine] offered the strongest correlation (p < 0.001) with pain joint count, swollen joint count and DAS 28. Such analysis of amino acid and related metabolite pattern offers potential for diagnosis as well as for monitoring disease progression and therapy in RA. PMID- 26811909 TI - Quantitative Genetics Identifies Cryptic Genetic Variation Involved in the Paternal Regulation of Seed Development. AB - Embryonic development requires a correct balancing of maternal and paternal genetic information. This balance is mediated by genomic imprinting, an epigenetic mechanism that leads to parent-of-origin-dependent gene expression. The parental conflict (or kinship) theory proposes that imprinting can evolve due to a conflict between maternal and paternal alleles over resource allocation during seed development. One assumption of this theory is that paternal alleles can regulate seed growth; however, paternal effects on seed size are often very low or non-existent. We demonstrate that there is a pool of cryptic genetic variation in the paternal control of Arabidopsis thaliana seed development. Such cryptic variation can be exposed in seeds that maternally inherit a medea mutation, suggesting that MEA acts as a maternal buffer of paternal effects. Genetic mapping using recombinant inbred lines, and a novel method for the mapping of parent-of-origin effects using whole-genome sequencing of segregant bulks, indicate that there are at least six loci with small, paternal effects on seed development. Together, our analyses reveal the existence of a pool of hidden genetic variation on the paternal control of seed development that is likely shaped by parental conflict. PMID- 26811911 TI - Germinoma Mimicking Tumefactive Demyelinating Disease in Pediatric Patients. AB - Cases of intracranial germinoma with granulomatous reaction are rare, so a pathological diagnosis of this disease is difficult. In this report, we describe the case of a 13-year-old boy with a bilateral thalamic germinoma which initially mimicked tumefactive demyelinating disease with inflammation, based on the clinical symptoms, imaging results and histology of a biopsy specimen obtained endoscopically. Upon examination of the cerebrospinal fluid, oligoclonal bands were detected. Although his symptoms and radiological findings improved following steroid pulse treatment, they worsened dramatically almost 1 year after the first surgery and even after an additional steroid pulse treatment. Prompted by the clinical course, a second biopsy was performed, and a pathological examination of the specimen showed a two-cell pattern. The diagnosis was changed to intracranial germinoma. After chemotherapeutic treatment with etoposide and cisplatin, the patient's symptoms and radiological findings dramatically improved. We conclude that it is very challenging to distinguish germinomas with a granulomatous reaction due to other inflammatory diseases, especially when only small specimens can be obtained. Stereotactic or endoscopic biopsies should be performed using samples from several different points even if the lesions are associated with eloquent brain regions. PMID- 26811914 TI - Diverse Tp*-Capped W-Cu-S Clusters from One-Pot Assembly Involving in Situ Thiolation of Phosphines. AB - In the absence/presence of S8, the one-pot assembly of [Et4N][Tp*WS3] [1; Tp* = hydridotris(3,5-dimethylpyrazol-1-yl)borate] with [Cu(MeCN)4]PF6 and bis- or tetraphosphine ligands 1,2-bis(diphenylphosphino)ethane (dppe), 1,3 bis(diphenylphosphino)propane (dppp), 1,4-bis(diphenylphosphino)butane (dppb), and N,N,N',N'-tetrakis(diphenylphosphinomethyl)ethylenediamine (dppeda) produces six W-Cu-S clusters, namely, [(Tp*WS3Cu2Cl)2(dppe)] (2), [Tp*WS3Cu4(dppp)2(MU4 Cl)(MU-Cl)]PF6.MeCN (3.MeCN), [(Tp*WS3Cu3)2(MU4-Cl)(MU-Cl)2(dpppS2)] (4), [(Tp*WS3Cu2Cl)2(dppbS2)].2MeCN.2H2O (5.2MeCN.2H2O), [(Tp*WS3Cu3Cl2)2(dppbS2)] (6), and [(Tp*WS3Cu3)2(Ph2PS2)3(MU6-Cl)0.5](PF6)0.5.0.75CH2Cl2 (7.0.75CH2Cl2). Compounds 2-7 are characterized by elemental analysis, IR, UV-vis, (1)H and (31)P{(1)H} NMR, electrospray ionization mass spectrometry, and X-ray crystallography. For 2, the dppe ligand bridges a pair of butterfly-shaped [Tp*WS3Cu2] cores to form a double-butterfly-shaped structure. For 4, the dppp ligand is susceptible toward S association and forms an in situ generated dpppS2 ligand, supporting an octanuclear double-half-open-cubane structure and contrasting an analogous system wherein a pentanuclear motorcycle-shaped cationic cluster 3 is formed with the absence of S8. A longer dppb ligand readily converts to S-based ligands in 5 and 6, subsequently serving as bridges between a pair of a butterfly-shaped (5) and nest-shaped (6) clusters. Further use of a tetraphosphine ligand, dppeda, in the cluster formation, with the presence of S8, leads to an unexpected ligand degradation to give the [Ph2PS2](-) anions. Three [Ph2PS2](-) anions juxtapose a pair of nest-shaped cluster cores to yield an octanuclear cluster, 7, featuring a cage to encapsulate MU6-Cl(-). The third order nonlinear-optical (NLO) properties of 2-7 in N,N-dimethylformamide, investigated using a Z-scan technique at 532 nm, show that 2-6 have a reverse saturable absorption, while 7 has a notable saturable absorption. All of 2-7 exhibit a self-focusing effect with hyperpolarizability gamma values in the range of 4.71 * 10(-30)-1.02 * 10(-29) esu, which are 440-1000 times higher than that of 1. The formation of 4-7 from 1 through the in situ thiolation of phosphine ligands presents a new approach to the design and assembly of the W-Cu-S clusters with interesting structural arrays and better NLO properties. PMID- 26811912 TI - A working model for the assessment of disruptions in social behavior among aged rats: The role of sex differences, social recognition, and sensorimotor processes. AB - Aging results in a natural decline in social behavior, yet little is known about the processes underlying these changes. Engaging in positive social interaction is associated with many health benefits, including reduced stress reactivity, and may serve as a potential buffer against adverse consequences of aging. The goal of these studies was to establish a tractable model for the assessment of social behavior deficits associated with late aging. Thus, in Exp. 1, 1.5-, 3-, and 18 month-old male Fischer 344 (F344) rats were assessed for object investigation, and social interaction with a same-aged partner (novel/familiar), or a different aged partner, thereby establishing working parameters for studies that followed. Results revealed that 18-month-old males exhibited reductions in social investigation and social contact behavior, with this age-related decline not influenced by familiarity or age of the social partner. Subsequently, Exp. 2 extended assessment of social behavior to both male and female F344 rats at multiple ages (3, 9, 18, and 24 months), after which a series of sensorimotor performance tests were conducted. In this study, both males and females exhibited late aging-related reductions in social interactions, but these changes were more pronounced in females. Additionally, sensorimotor performance was shown to be impaired in 24-month-olds, but not 18-month-olds, with this deficit more evident in males. Finally, Exp. 3 examined whether aging-related inflammation could account for declines in social behavior during late aging by administering naproxen (0, 7, 14, and 28 mg/kg; s.c.)-a non-steroidal anti-inflammatory drug-to 18-month-old females. Results from this study revealed that social behavior was unaffected by acute or repeated (6 days) naproxen, suggesting that aging-related social deficits in females may not be a consequence of a general aging-related inflammation and/or malaise. Together, these findings demonstrate that aging related declines in social behavior are (i) specific to social stimuli and (ii) not indicative of a general state of aging-related debilitation. Thus, these findings establish working parameters for a highly tractable model in which the neural and hormonal mechanisms underlying aging-related declines in social behavior can be examined. PMID- 26811913 TI - Early Life Origins of Lung Ageing: Early Life Exposures and Lung Function Decline in Adulthood in Two European Cohorts Aged 28-73 Years. AB - OBJECTIVES: Early life environment is essential for lung growth and maximally attained lung function. Whether early life exposures impact on lung function decline in adulthood, an indicator of lung ageing, has scarcely been studied. METHODS: Spirometry data from two time points (follow-up time 9-11 years) and information on early life exposures, health and life-style were available from 12862 persons aged 28-73 years participating in the European population-based cohorts SAPALDIA (n = 5705) and ECRHS (n = 7157). The associations of early life exposures with lung function (FEV1) decline were analysed using mixed-effects linear regression. RESULTS: Early life exposures were significantly associated with FEV1 decline, with estimates almost as large as personal smoking. FEV1 declined more rapidly among subjects born during the winter season (adjusted difference in FEV1/year of follow-up [95%CI] -2.04ml [-3.29;-0.80]), of older mothers, (-1.82 ml [-3.14;-0.49]) of smoking mothers (-1.82ml [-3.30;-0.34] or with younger siblings (-2.61ml [-3.85;-1.38]). Less rapid FEV1-decline was found in subjects who had attended daycare (3.98ml [2.78;5.18]), and indicated in subjects with pets in childhood (0.97ml [-0.16;2.09]). High maternal age and maternal smoking appeared to potentiate effects of personal smoking. The effects were independent of asthma at any age. CONCLUSION: Early life factors predicted lung function decline decades later, suggesting that some mechanisms related lung ageing may be established early in life. Early life programming of susceptibility to adult insults could be a possible pathway that should be explored further. PMID- 26811915 TI - Staphylococcus aureus and Staphylococcus epidermidis Virulence Strains as Causative Agents of Persistent Infections in Breast Implants. AB - Staphylococcus epidermidis and Staphylococcus aureus are currently considered two of the most important pathogens in nosocomial infections associated with catheters and other medical implants and are also the main contaminants of medical instruments. However because these species of Staphylococcus are part of the normal bacterial flora of human skin and mucosal surfaces, it is difficult to discern when a microbial isolate is the cause of infection or is detected on samples as a consequence of contamination. Rapid identification of invasive strains of Staphylococcus infections is crucial for correctly diagnosing and treating infections. The aim of the present study was to identify specific genes to distinguish between invasive and contaminating S. epidermidis and S. aureus strains isolated on medical devices; the majority of our samples were collected from breast prostheses. As a first step, we compared the adhesion ability of these samples with their efficacy in forming biofilms; second, we explored whether it is possible to determine if isolated pathogens were more virulent compared with international controls. In addition, this work may provide additional information on these pathogens, which are traditionally considered harmful bacteria in humans, and may increase our knowledge of virulence factors for these types of infections. PMID- 26811917 TI - Reply to 'PTX-3 release is increased by monocytes from patients with primary fibromyalgia without major depression' by J.J. Garcia et al. PMID- 26811919 TI - Life-Cycle Assessment of Biodiesel Produced from Grease Trap Waste. AB - Grease trap waste (GTW) is a low-quality waste material with variable lipid content that is an untapped resource for producing biodiesel. Compared to conventional biodiesel feedstocks, GTW requires different and additional processing steps for biodiesel production due to its heterogeneous composition, high acidity, and high sulfur content. Life-cycle assessment (LCA) is used to quantify greenhouse gas emissions, fossil energy demand, and criteria air pollutant emissions for the GTW-biodiesel process, in which the sensitivity to lipid concentration in GTW is analyzed using Monte Carlo simulation. The life cycle environmental performance of GTW-biodiesel is compared to that of current GTW disposal, the soybean-biodiesel process, and low-sulfur diesel (LSD). The disposal of the water and solid wastes produced from separating lipids from GTW has a high contribution to the environmental impacts; however, the impacts of these processed wastes are part of the current disposal practice for GTW and could be excluded with consequential LCA system boundaries. At lipid concentrations greater than 10%, most of the environmental metrics studied are lower than those of LSD and comparable to soybean biodiesel. PMID- 26811920 TI - JAYAO: Not Your Average Cancer Population, Not Your Average Journal. PMID- 26811916 TI - A Genome-Wide mRNA Expression Profile in Caenorhabditis elegans under Prolonged Exposure to 1750MHz Radiofrequency Fields. AB - OBJECTIVE: C. elegans has been used as a biomonitor for microwave-induced stress. However, the RF (radiofrequency) fields that have been used in previous studies were weak (<=1.8W/kg), and the bio-effects on C. elegans were mostly negative or ambiguous. Therefore, this study used more intense RF fields (SAR = 3W/kg) and longer time course of exposure (60h at 25 degrees C, L1 stage through adult stage) to investigate the biological consequences of 1750 MHz RF fields in wild type worms. METHODS: The growth rates and lifespans of RF-exposure group and the control group were carefully recorded. RNA samples were collected at L4 (35h) and gravid adult (50h) stages for further high-throughput sequencing, focusing on differences between the RF-exposure and the sham control groups. RESULTS: The RF exposed and sham control groups developed at almost the same rate and had similar longevity curves. In L4 stage worms, 94 up-regulated and 17 down-regulated genes were identified, while 186 up-regulated and 3 down-regulated genes were identified in adult stage worms. GO analysis showed that the differentially expressed genes at 35h were associated with growth, body morphogenesis and collagen and cuticle-based development. Genes that were linked to growth rate and reproductive development were differentially expressed at 50h. Some embryonic and larval development genes in the offspring were also differentially expressed at 50h. Ten genes were differentially expressed at both 35h and 50h, most of which were involved in both embryonic and larval developmental processes. Although prolonged RF fields did not induce significant temperature increase in RF exposure groups, the temperature inside worms during exposure was unknown. CONCLUSIONS: No harmful effects were observed in prolonged exposure to 1750 MHz RF fields at SAR of 3W/kg on development and longevity of C. elegans. Although some differentially expressed genes were found after prolonged RF exposure, these differences were ascribed to oscillating gene expression patterns in L4 and gravid adult worms. It was also difficult to rule out a weak thermal effect caused by prolonged RF exposure inside the worms. PMID- 26811921 TI - Responding to Adolescents with Cancer who Refuse Sperm Banking: When "No" Should Not Be the Last Word. PMID- 26811918 TI - Invasive Group A Streptococcus Infection among Children, Rural Kenya. AB - To determine the extent of group A Streptococcus (GAS) infections in sub-Saharan Africa and the serotypes that cause disease, we analyzed surveillance data for 64,741 hospital admissions in Kilifi, Kenya, during 1998-2011. We evaluated incidence, clinical presentations, and emm types that cause invasive GAS infection. We detected 370 cases; of the 369 for which we had data, most were skin and soft tissue infections (70%), severe pneumonia (23%), and primary bacteremia (14%). Overall case-fatality risk was 12%. Incidence of invasive GAS infection was 0.6 cases/1,000 live births among neonates, 101/100,000 person years among children <1 year of age, and 35/100,000 among children <5 years of age. Genome sequencing identified 88 emm types. GAS causes serious disease in children in rural Kenya, especially neonates, and the causative organisms have considerable genotypic diversity. Benefit from the most advanced GAS type specific vaccines may be limited, and efforts must be directed to protect against disease in regions of high incidence. PMID- 26811922 TI - Workshop Report on the European Bone Sarcoma Networking Meeting: Integration of Clinical Trials with Tumor Biology. AB - A key workshop was held in The Netherlands in June 2011, hosted by several European bone sarcoma networks and with a broad range of stakeholders from Europe and Australia. The purpose of the meeting was to identify the strengths and weaknesses in current clinical trials for bone sarcomas and to make recommendations as to how to accelerate progress in this field. Two areas of particular interest were discussed. First, all participants agreed upon the importance of tumor biology to understanding clinical responses for all types of bone sarcoma. Various barriers to biobanking tumor and germline specimens were canvassed and are outlined in this paper. Second, there was consideration of the particular challenges of dealing with adolescent and young adult cancers, exemplified by bone sarcomas. Participants recommended greater engagement of both pediatric and adult sarcoma trial organizations to address this issue. Specific opportunities were identified to develop biological sub-studies within osteosarcoma, focused on understanding germ line risk and pharmacogenomics defining toxicity and biological responses. In Ewing sarcoma, it was harder to define opportunities for biological insights. There was agreement that the results for insulin-like growth factor pathway inhibition in Ewing family tumors were disappointing, but represented a clear indication of the need for companion biologic studies to develop predictive biomarkers. The meeting ended with broad commitment to working together to make progress in this rare but important subgroup of cancers. PMID- 26811923 TI - Practices and Resources Devoted to the Care of Adolescents and Young Adults with Cancer in Canada: A Survey of Pediatric and Adult Cancer Treatment Centers. AB - PURPOSE: Adolescents and young adults (AYAs) with cancer are a population of patients facing disparities of care affecting quality of life and other health outcomes. Our objective was to document the current environment, resources, and services available to and challenges in the care of these patients in Canada. METHODS: A questionnaire was developed with separate versions for pediatric and adult cancer centers. We invited one individual from every healthcare center providing cancer care in Canada to complete the questionnaire on behalf of his or her center. The survey included questions about referral patterns, diagnosis, treatment options, the nature of the challenges faced when treating AYAs with cancer, collaborative initiatives between pediatric and adult oncologists, and the presence of dedicated AYA resources and staff. RESULTS: We identified a lack of resources, staff, and collaborative activities dedicated to AYAs with cancer throughout Canada, both in pediatric and adult centers. Adult medical oncologists reported experiencing different challenges in treating AYAs with cancer compared to pediatric practitioners. CONCLUSIONS: Efforts to enhance AYA oncology care, including better resources and staffing and improved collaboration between pediatric and adult centers, are required. PMID- 26811925 TI - [Not Available]. PMID- 26811924 TI - "Your Place or Mine?" Priorities for a Specialist Teenage and Young Adult (TYA) Cancer Unit: Disparity Between TYA and Professional Perceptions. AB - PURPOSE: To identify key components of a specialist teenager and young adult (TYA) cancer unit from the perspective of young people and health professionals. PATIENTS AND METHODS: A facilitated workshop was held in England at which participants prioritized 15 core features of a specialist cancer unit identified in a literature review. Themes were transferred onto cards and organized using a pyramid. Notes were made of the discussion and how decisions were reached. The exercise was repeated in a survey at a patient conference. Data were analyzed by weighting the ranked position and by content analysis. RESULTS: Eleven young people and 22 health professionals attended the workshops, and 64 young people completed the survey. Young people's top three priorities were a dedicated unit, contact with peers, and provision for partners/parents to live in the unit with them. Health professionals prioritized best chance of survival and best quality of life, access to expertise, access to computers/Internet, and age-appropriate equipment. CONCLUSIONS: Priorities varied across and within healthcare professionals and young people, and were dependent on viewpoint and personal experience. This is an essential first step toward a fuller description of the benefit of specialist TYA cancer services and highlights the importance of consulting users in service development. PMID- 26811926 TI - Transdermal Diagnosis of Malaria Using Vapor Nanobubbles. PMID- 26811927 TI - Experimental and Theoretical Electron Density Analysis of Copper Pyrazine Nitrate Quasi-Low-Dimensional Quantum Magnets. AB - The accurate electron density distribution and magnetic properties of two metal organic polymeric magnets, the quasi-one-dimensional (1D) Cu(pyz)(NO3)2 and the quasi-two-dimensional (2D) [Cu(pyz)2(NO3)]NO3.H2O, have been investigated by high resolution single-crystal X-ray diffraction and density functional theory calculations on the whole periodic systems and on selected fragments. Topological analyses, based on quantum theory of atoms in molecules, enabled the characterization of possible magnetic exchange pathways and the establishment of relationships between the electron (charge and spin) densities and the exchange coupling constants. In both compounds, the experimentally observed antiferromagnetic coupling can be quantitatively explained by the Cu-Cu superexchange pathway mediated by the pyrazine bridging ligands, via a sigma-type interaction. From topological analyses of experimental charge-density data, we show for the first time that the pyrazine tilt angle does not play a role in determining the strength of the magnetic interaction. Taken in combination with molecular orbital analysis and spin density calculations, we find a synergistic relationship between spin delocalization and spin polarization mechanisms and that both determine the bulk magnetic behavior of these Cu(II)-pyz coordination polymers. PMID- 26811928 TI - Heterozygote Advantage Probably Maintains Rhesus Factor Blood Group Polymorphism: Ecological Regression Study. AB - Rhesus factor polymorphism has been an evolutionary enigma since its discovery in 1939. Carriers of the rarer allele should be eliminated by selection against Rhesus positive children born to Rhesus negative mothers. Here I used an ecologic regression study to test the hypothesis that Rhesus factor polymorphism is stabilized by heterozygote advantage. The study was performed in 65 countries for which the frequencies of RhD phenotypes and specific disease burden data were available. I performed multiple multivariate covariance analysis with five potential confounding variables: GDP, latitude (distance from the equator), humidity, medical care expenditure per capita and frequencies of smokers. The results showed that the burden associated with many diseases correlated with the frequencies of particular Rhesus genotypes in a country and that the direction of the relation was nearly always the opposite for the frequency of Rhesus negative homozygotes and that of Rhesus positive heterozygotes. On the population level, a Rhesus-negativity-associated burden could be compensated for by the heterozygote advantage, but for Rhesus negative subjects this burden represents a serious problem. PMID- 26811930 TI - LC-MS/MS multiplexed assay for the quantitation of a therapeutic protein BMS 986089 and the target protein Myostatin. AB - BACKGROUND: Therapeutic protein discovery study highlights the need for the development of quantitative bioanalytical methods for determining the levels of both the therapeutic protein and the target protein, as well. RESULTS: For the quantitation of BMS-986089, both accuracy (99-103%) and precision (2.4-12%) were obtained for the analysis of the surrogate peptide (ITYGGNSPVQEFTVPGR), in addition to the accuracy (100-108%) and precision (0.7-18%) that were obtained for the analysis of the surrogate peptide (VVSVLTVLHQDWLNGK). For Myostatin, accuracy (94-103%) and precision (2.4-14.9%) were obtained for the analysis of the surrogate peptide (IPAMVVDR). CONCLUSION: The developed method was applied to the analysis of samples following dosing of BMS-986089 to mice. This method highlights the potential of LC-MS/MS-based methods to eventually assess in vivo drug-target engagement. PMID- 26811929 TI - Observational Study of Obstructive Sleep Apnea in Wake-Up Stroke: The SLEEP TIGHT Study. AB - BACKGROUND: Wake-up stroke (WUS) accounts for a quarter of all ischemic strokes. Its conspicuous occurrence during sleep suggests that WUS may be associated with obstructive sleep apnea (OSA). We investigated the potential association among WUS, OSA, and measures of sympathetic hyperactivity. METHODS: This is a cross sectional analysis of data from the Sleep Apnea in Transient Ischemic Attack and Stroke (SLEEP TIGHT) study. Ischemic stroke patients were divided into WUS and non-WUS groups. Participants underwent polysomnography and ambulatory blood pressure monitoring. Collected data included demographic, medical, stroke characteristics (including severity by National Institutes of Health Stroke Scale), cholesterol, serum catecholamines, C-reactive protein, interleukin-6, B type natriuretic peptide, blood pressure, and polysomnographic (apnea-hypopnea index (AHI); measures of hypoxia). Because both stroke and OSA affect men and women to varying degrees, the cohort was considered as a whole and by gender stratification. RESULTS: Among 164 participants, 30.3% had WUS. The mean age was 62.0 +/- 11.3 and the mean body mass index was 30.2 +/- 7.9 kg/m2. One-hundred and-five participants (63.6%) were males and 92 participants (56.8%) were Caucasian. Neither AHI nor OSA (AHI >=5) frequency differed between WUS and non WUS groups. Men tended to be more likely than women to have WUS (74.0 vs. 59.6%; p = 0.08), but this was not statistically significant. In gender-stratified analyses, men with WUS compared to men with non-WUS had significantly higher rates of severe OSA (AHI >30: 45.0 vs. 17.6%; p = 0.03) and tended toward more 3% oxygen desaturation events (57.0 +/- 63.9 vs. 31.8 +/- 22.9; p = 0.06). These differences were not seen in women. WUS patients tended to be of the male gender (74.0 vs. 59.6%; p = 0.08). History of stroke, hypertension, diabetes, dyslipidemia, or atrial fibrillation, serum catecholamines, and inflammatory biomarkers was no different between the groups. Low-density lipoprotein (LDL) was significantly higher in WUS (114.5 +/- 36.3 vs. 101.4 +/- 37.6; p = 0.04). Baseline diastolic blood pressure (DBP) was significantly greater in the WUS group. There was no difference in systolic or ambulatory blood pressure (including nighttime blood pressure) between WUS and non-WUS groups. CONCLUSIONS: WUS may be associated with severe OSA with more oxygen desaturation in men but not in women. WUS may be associated with high DBP and increased LDL cholesterol. PMID- 26811932 TI - A simple modification of PCR thermal profile applied to evade persisting contamination. AB - The polymerase chain reaction (PCR), one of the most commonly applied methods of diagnostics and molecular biology has a frustrating downside known as the false positive signal or contamination. Several solutions to avoid and to eliminate PCR contaminations have been worked out to date but the implementation of these solutions to laboratory practice may be laborious and time consuming. A simple approach to circumvent the problem of persisting PCR contamination is reported. The principle of this approach lies in shortening the steps of denaturation, annealing, and elongation in the PCR thermal cycle. The modification leads to the radical decline of false positive signals obtained for the no-template controls without affecting the detection of target PCR products. In the model experiments presented here, the signal of negative control was shifted by about ten cycles up above those for the examined samples so that it could be neglected. We do not recommend this solution in PCR diagnostics, where the sensitivity of detection is of the highest priority. However, the approach could be useful to pass by the problem of persisting contamination in quantitative PCR, where the range of quantitation is usually much above the limits of detection. PMID- 26811931 TI - Fibronectin Deposition Participates in Extracellular Matrix Assembly and Vascular Morphogenesis. AB - The extracellular matrix (ECM) has been demonstrated to facilitate angiogenesis. In particular, fibronectin has been documented to activate endothelial cells, resulting in their transition from a quiescent state to an active state in which the cells exhibit enhanced migration and proliferation. The goal of this study is to examine the role of polymerized fibronectin during vascular tubulogenesis using a 3 dimensional (3D) cell-derived de-cellularized matrix. A fibronectin rich 3D de-cellularized ECM was used as a scaffold to study vascular morphogenesis of endothelial cells (ECs). Confocal analyses of several matrix proteins reveal high intra- and extra-cellular deposition of fibronectin in formed vascular structures. Using a small peptide inhibitor of fibronectin polymerization, we demonstrate that inhibition of fibronectin fibrillogenesis in ECs cultured atop de-cellularized ECM resulted in decreased vascular morphogenesis. Further, immunofluorescence and ultrastructural analyses reveal decreased expression of stromal matrix proteins in the absence of polymerized fibronectin with high co-localization of matrix proteins found in association with polymerized fibronectin. Evaluating vascular kinetics, live cell imaging showed that migration, migration velocity, and mean square displacement, are disrupted in structures grown in the absence of polymerized fibronectin. Additionally, vascular organization failed to occur in the absence of a polymerized fibronectin matrix. Consistent with these observations, we tested vascular morphogenesis following the disruption of EC adhesion to polymerized fibronectin, demonstrating that block of integrins alpha5beta1 and alphavbeta3, abrogated vascular morphogenesis. Overall, fibronectin deposition in a 3D cell derived de-cellularized ECM appears to be imperative for matrix assembly and vascular morphogenesis. PMID- 26811934 TI - The efficacy and safety of rufinamide in drug-resistant epilepsy: A meta-analysis of double-blind, randomized, placebo controlled trials. AB - OBJECTIVE: To evaluate the clinical efficacy and safety of rufinamide in drug resistant epilepsy. METHODS: We searched PubMed, Web of Science and Clinical trial.org up to August 6, 2015. Study selection, extraction and risk of bias assessment were performed independently by two authors. A random or fixed-effect model was used to derive pooled effects risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Five randomized controlled trials were included in the final analysis with a total of 1512 patients. Rufinamide increased the 50% (RR 1.852, 95%CI 1.446-2.372, P<0.001) and 75% (RR 8.547, 95%CI 2.534-28.832, P<0.001) responder rates but not the seizure-free rate (RR 1.740, 95%CI 0.511 5.924, P=0.376) compared to placebo. Subgroup analysis demonstrated that the effect of rufinamide may be dose-dependent and related to seizure type. Regarding safety, rufinamide increased the rate of at least one adverse event (RR 1.103, 95%CI 1.047-1.161, P<0.001) and the withdrawal rate due to adverse events (RR 2.341, 95%CI 1.556-3.522, P<0.001), but it did not increase the rate of severe adverse events (RR 1.454, 95%CI 0.945-2.241, P=0.090). Individual adverse events (headache, dizziness, fatigue, somnolence, nausea, diplopia and vomiting) were significantly higher in the rufinamide group. CONCLUSIONS: This study confirmed significant effects of rufinamide as adjunctive treatment for drug-resistant seizures, both partial and tonic-atonic. However, rufinamide may induce more tolerable (but not severe) adverse events. Further large clinical trials to investigate the long-term efficacy and safety of rufinamide are warranted. PMID- 26811933 TI - Active immunisation targeting soluble murine tumour necrosis factor alpha is safe and effective in collagen-induced arthritis model treatment. AB - OBJECTIVES: TNF-alpha has been proved to be an effective target in rheumatoid arthritis treatment. So far, all the commercialised TNF-alpha antagonists function as passive immunotherapy. The aim of this study was to design a complex which can trigger active immunisation and overcome self-tolerance to elicit antibodies against murine TNF-alpha. METHODS: The complex (KLH-TNF) was chemically synthesised by linking a selected peptide TNFalpha(4-23) from murine soluble TNF-alpha to a carrier protein, keyhole limpet haemocyanin (KLH). We evaluated its safety and antibody eliciting performance. We also evaluated its disease-regulating ability on collagen-induced arthritis models. Furthermore, the immune cells responses were analysed by T cell proliferation assay and B cell memory experiments. RESULTS: The complex was safe without cytotoxity. The anti mTNF-alpha antibody titers of the KLH-TNF group were 400 times greater than the control groups (p<0.0001). The elicited antibodies could combine with soluble TNF alpha. The antibody response was independent of autologous TNF-alpha and could be reinforced by booster immunisation. Moreover, the complex did not trigger T cell activation and B cell memory response against native TNF-alpha. In animal experiments, KLH-TNF immunized mice showed a lower arthritis score (p<0.001) and better weight gain (p<0.01). Histological evaluations showed milder inflammation and cartilage depletion. CONCLUSIONS: Active immunotherapy against cytokine TNF alpha is feasible by conjugating cytokine peptide with carrier protein. The elicited antibodies could combine with the native TNF-alpha and inhibit its activity. Importantly, the antibody response is reversible and independent of autologous TNF-alpha. PMID- 26811935 TI - Visible Light Image-Based Method for Sugar Content Classification of Citrus. AB - Visible light imaging of citrus fruit from Mie Prefecture of Japan was performed to determine whether an algorithm could be developed to predict the sugar content. This nondestructive classification showed that the accurate segmentation of different images can be realized by a correlation analysis based on the threshold value of the coefficient of determination. There is an obvious correlation between the sugar content of citrus fruit and certain parameters of the color images. The selected image parameters were connected by addition algorithm. The sugar content of citrus fruit can be predicted by the dummy variable method. The results showed that the small but orange citrus fruits often have a high sugar content. The study shows that it is possible to predict the sugar content of citrus fruit and to perform a classification of the sugar content using light in the visible spectrum and without the need for an additional light source. PMID- 26811938 TI - Efficient Water Splitting Catalyzed by Cobalt Phosphide-Based Nanoneedle Arrays Supported on Carbon Cloth. AB - Efficient and low-cost electrocatalysts for water splitting are essential for solar fuel production. Herein, we report that nanoarrays of CoP supported on carbon cloth are an efficient bifunctional catalyst for overall water splitting. The catalyst exhibits remarkable activity for both the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in alkaline media, delivering a current density of 10 mA cm(-2) at an overpotential of 281 mV for OER and 95 mV for HER. During electrocatalysis, the surface of the CoP catalyst was covered with a layer of CoOx , which was the active species. However, the CoP core and the nanoarray morphology contributed significantly to the activity. PMID- 26811936 TI - Ionically Cross-Linked Polymer Networks for the Multiple-Month Release of Small Molecules. AB - Long-term (multiple-week or -month) release of small, water-soluble molecules from hydrogels remains a significant pharmaceutical challenge, which is typically overcome at the expense of more-complicated drug carrier designs. Such approaches are payload-specific and include covalent conjugation of drugs to base materials or incorporation of micro- and nanoparticles. As a simpler alternative, here we report a mild and simple method for achieving multiple-month release of small molecules from gel-like polymer networks. Densely cross-linked matrices were prepared through ionotropic gelation of poly(allylamine hydrochloride) (PAH) with either pyrophosphate (PPi) or tripolyphosphate (TPP), all of which are commonly available commercial molecules. The loading of model small molecules (Fast Green FCF and Rhodamine B dyes) within these polymer networks increases with the payload/network binding strength and with the PAH and payload concentrations used during encapsulation. Once loaded into the PAH/PPi and PAH/TPP ionic networks, only a few percent of the payload is released over multiple months. This extended release is achieved regardless of the payload/network binding strength and likely reflects the small hydrodynamic mesh size within the gel-like matrices. Furthermore, the PAH/TPP networks show promising in vitro cytocompatibility with model cells (human dermal fibroblasts), though slight cytotoxic effects were exhibited by the PAH/PPi networks. Taken together, the above findings suggest that PAH/PPi and (especially) PAH/TPP networks might be attractive materials for the multiple-month delivery of drugs and other active molecules (e.g., fragrances or disinfectants). PMID- 26811939 TI - Endoscopic disruption of an anastomotic diaphragm in ulcerative colitis. PMID- 26811940 TI - Pediatric application of the lumen-apposing metal stent for pancreatic fluid collections. PMID- 26811937 TI - Associations between Tobacco, Alcohol, and Drug Use with Coronary Artery Plaque among HIV-Infected and Uninfected Men in the Multicenter AIDS Cohort Study. AB - BACKGROUND: We characterized associations between smoking, alcohol, and recreational drug use and coronary plaque by HIV serostatus within the Multicenter AIDS Cohort Study (MACS). METHODS: MACS participants (N = 1005, 621 HIV+ and 384 HIV-) underwent non-contrast CT scanning to measure coronary artery calcium; 764 underwent coronary CT angiograms to evaluate plaque type and extent. Self-reported use of alcohol, tobacco, smoked/inhaled cocaine, methamphetamine, ecstasy, marijuana, inhaled nitrites, and erectile dysfunction drugs was obtained at semi-annual visits beginning 10 years prior to CT scanning. Multivariable logistic and linear regression models were performed, stratified by HIV serostatus. RESULTS: Among HIV+ men, current smoking, former smoking, and cumulative pack years of smoking were positively associated with multiple coronary plaque measures (coronary artery calcium presence and extent, total plaque presence and extent, calcified plaque presence, and stenosis >50%). Smoking was significantly associated with fewer plaque measures of comparable effect size among HIV- men; current smoking and calcified plaque extent was the only such association. Heavy alcohol use (>14 drinks/week) was associated with stenosis >50% among HIV+ men. Among HIV- men, low/moderate (1-14 drinks/week) and heavy alcohol use were inversely associated with coronary artery calcium and calcified plaque extent. Few significant associations between other recreational drug use and plaque measures were observed. CONCLUSION: Smoking is strongly associated with coronary plaque among HIV+ men, underscoring the value of smoking cessation for HIV+ persons. Alcohol use may protect against coronary artery calcium and calcified plaque progression in HIV- (but not HIV+) men. Few positive associations were observed between recreational drug use and coronary plaque measures. PMID- 26811942 TI - Excited State Proton Transfer and Deactivation Mechanism of 2-(4'-Amino-2' hydroxyphenyl)-1H-imidazo-[4,5-c]pyridine and Its Analogues: A Theoretical Study. AB - In the present study, the results of comprehensive theoretical exploration on the nonradiative relaxation of three (hydroxyphenyl)imidazole-based organic compounds (abbreviated AHP, HPIP, and HPBI) in the gas phase are presented. Having small structural differences, the selected systems have commonalities in the excited state intramolecular proton transfer (ESIPT) process. The ground and S1 excited state potential energy profiles of titled systems have been determined on the basis of the RI-MP2 and RI-CC2 methods, and the effect of small structural distinctions on their photophysical characters will be extensively addressed. Although, in the presence of solvent, high fluorescence quantum yield is another characteristic of AHP and HPIP, owing to accessible conical intersections between the S1/S0 state potential energy profiles of both systems, nonradiative relaxation can be proposed as the most important feature of these two systems in the gas phase. These conical intersections are responsible for ultrafast deactivation of excited systems via internal conversions to the ground state. The nonradiative deactivation mechanism determined in this work deals with the remarkable photostability of the AHP and HPIP molecules. PMID- 26811941 TI - Frequency and Distribution of Rickettsiae, Borreliae, and Ehrlichiae Detected in Human-Parasitizing Ticks, Texas, USA. AB - To describe the presence and distribution of tickborne bacteria and their vectors in Texas, USA, we screened ticks collected from humans during 2008-2014 for Rickettsia, Borrelia, and Ehrlichia spp. Thirteen tick species were identified, and 23% of ticks carried bacterial DNA from at least 1 of the 3 genera tested. PMID- 26811943 TI - Multicomponent Supramolecular Polymers as a Modular Platform for Intracellular Delivery. AB - Supramolecular polymers are an emerging family of nanosized structures with potential use in materials chemistry and medicine. Surprisingly, application of supramolecular polymers in the field of drug delivery has received only limited attention. Here, we explore the potential of PEGylated 1,3,5 benzenetricarboxamide (BTA) supramolecular polymers for intracellular delivery. Exploiting the unique modular approach of supramolecular chemistry, we can coassemble neutral and cationic BTAs and control the overall properties of the polymer by simple monomer mixing. Moreover, this platform offers a versatile approach toward functionalization. The core can be efficiently loaded with a hydrophobic guest molecule, while the exterior can be electrostatically complexed with siRNA. It is demonstrated that both compounds can be delivered in living cells, and that they can be combined to enable a dual delivery strategy. These results show the advantages of employing a modular system and pave the way for application of supramolecular polymers in intracellular delivery. PMID- 26811945 TI - Candidatus Coxiella massiliensis Infection. AB - Bacteria genetically related to Coxiella burnetii have been found in ticks. Using molecular techniques, we detected Coxiella-like bacteria, here named Candidatus Coxiella massiliensis, in skin biopsy samples and ticks removed from patients with an eschar. This organism may be a common agent of scalp eschar and neck lymphadenopathy after tick bite. PMID- 26811944 TI - Role of Annular Lipids in the Functional Properties of Leucine Transporter LeuT Proteomicelles. AB - Recent work has shown that the choice of the type and concentration of detergent used for the solubilization of membrane proteins can strongly influence the results of functional experiments. In particular, the amino acid transporter LeuT can bind two substrate molecules in low concentrations of n-dodecyl beta-d maltopyranoside (DDM), whereas high concentrations reduce the molar binding stoichiometry to 1:1. Subsequent molecular dynamics (MD) simulations of LeuT in DDM proteomicelles revealed that DDM can penetrate to the extracellular vestibule and make stable contacts in the functionally important secondary substrate binding site (S2), suggesting a potential competitive mechanism for the reduction in binding stoichiometry. Because annular lipids can be retained during solubilization, we performed MD simulations of LeuT proteomicelles at various stages of the solubilization process. We find that at low DDM concentrations, lipids are retained around the protein and penetration of detergent into the S2 site does not occur, whereas at high concentrations, lipids are displaced and the probability of DDM binding in the S2 site is increased. This behavior is dependent on the type of detergent, however, as we find in the simulations that the detergent lauryl maltose-neopentyl glycol, which is approximately twice the size of DDM and structurally more closely resembles lipids, does not penetrate the protein even at very high concentrations. We present functional studies that confirm the computational findings, emphasizing the need for careful consideration of experimental conditions, and for cautious interpretation of data in gathering mechanistic information about membrane proteins. PMID- 26811946 TI - Enantiomorphous Periodic Mesoporous Organosilica-Based Nanocomposite Hydrogel Scaffolds for Cell Adhesion and Cell Enrichment. AB - The chemical functionalization of nanomaterials with bioactive molecules has been used as an effective tool to mimic extracellular matrix (ECM) and to study the cell-material interaction in tissue engineering applications. In this respect, this study demonstrates the use of enantiomerically functionalized periodic mesoporous organosilicas (PMO) for the generation of new multifunctional 3D nanocomposite (NC) hydrogels to control the affinity of cells to the hydrogel surfaces and so to control the enrichment of cells and simultaneous drug delivery in 3D network. The functionalization of PMO with enantiomers of bioactive molecules, preparation of their nanocomposite hydrogels, and the stereoselective interaction of them with selected cell types are described. The results show that the affinity of cells to the respective NC hydrogel scaffolds is affected by the nature of the biomolecule and its enantiomers, which is more pronounced in serum containing media. The differentiation of enantiomorphous NC hydrogels by cells is used to enrich one cell type from a mixture of two cells. Finally, PMO are utilized as nanocontainers to release two different dye molecules as a proof of principle for multidrug delivery in 3D NC hydrogel scaffolds. PMID- 26811947 TI - Ultrasound-guided pulsed radiofrequency treatment of the pudendal nerve in chronic pelvic pain. AB - Chronic pelvic pain is a condition that can be caused by pudendal neuralgia, interstitial cystitis, piriformis syndrome and neuropathy of the ilioinguinal, iliohypogastric and genitofemoral nerves. Based on three case reports this article discusses the clinical effectiveness of pulsed high-frequency radiofrequency (PRF) treatment applied to the pudendal nerve under ultrasound guidance in medicinally treated patients with chronic pelvic pain. PMID- 26811948 TI - [Sepsis caused by Raoultella ornithinolytica in an immunocompetent patient]. AB - Raoultella ornithinolytica is a species of gram-negative encapsulated and aerobic bacteria belonging to the family Enterobacteriaceae and is mainly found in fish. The most distinctive feature of this bacterium is the ability to convert histidine to histamine; therefore, the consumption of decomposing fish infected by R. ornithinolytica causes rashes, diarrhea, flushing, sweating and vomiting. This food poisoning is also called histamine fish poisoning; however, human infections with R. ornithinolytica are extremely rare and have so far only affected patients with diseases suppressing the immune system. The current case report describes for the first time sepsis with evidence of bloodstream infection by R. ornithinolytica in an immunocompetent male patient and the successful antibiotic treatment. PMID- 26811949 TI - [Preoperative patient-oriented advance planning of emergency and intensive care treatment--Necessary or imposition? : Questionnaire survey]. AB - BACKGROUND: Traditional advance directives can often not be satisfactorily implemented into patient care; therefore, patient-oriented decision-making prior to scheduled interventions and beyond the actual surgery is of particular importance. Data on inpatient advance care planning (ACP) in Germany are lacking. OBJECTIVES: This proof-of-concept study was carried out to determine the needs of inpatients undergoing surgery for advance preoperative planning of emergency care and to assess potential discomfort caused by such a program. MATERIAL AND METHODS: A voluntary and anonymous standardized questionnaire survey was carried out in scheduled surgery inpatients over 50 years old. Data collection was structured in a demographic part and statements dealing with preoperative advance planning of emergency care in hospital evaluated as Likert items. RESULTS: Out of 579 patients (mean age 66 years, 51% male) 43% indicated a basic interest in being informed about advance planning of emergency care individually during the current hospital stay. Desire for patient self-determination represented an independent factor of information needs [p = 0.036, 95% confidence interval (95% CI) 0.027-0.793]. The survey was perceived as a burden by only 7.3% of patients. This perception was independently associated with less concern about perioperative complication risks (p = 0.008, 95% CI 0.144-0.975). CONCLUSION: The results confirmed a substantial interest in patient-oriented advance planning of emergency care in a preoperative setting; however, no demographic group criteria for patients with information requirements could be defined. As the burden evoked by the topic is low, advance planning of emergency and intensive care treatment of inpatients undergoing surgery should be actively provided in the future. PMID- 26811950 TI - Live Bacterial Physiology Visualized with 5 nm Resolution Using Scanning Transmission Electron Microscopy. AB - It is now possible to visualize at nanometer resolution the infection of a living biological cell with virus without compromising cell viability using scanning transmission electron microscopy (STEM). To provide contrast while preserving viability, Escherichia coli and P1 bacteriophages were first positively stained with a very low concentration of uranyl acetate in minimal phosphate medium and then imaged with low-dose STEM in a microfluidic liquid flow cell. Under these conditions, it was established that the median lethal dose of electrons required to kill half the tested population was LD50 = 30 e(-)/nm(2), which coincides with the disruption of a wet biological membrane, according to prior reports. Consistent with the lateral resolution and high-contrast signal-to-noise ratio (SNR) inferred from Monte Carlo simulations, images of the E. coli membrane, flagella, and the bacteriophages were acquired with 5 nm resolution, but the cumulative dose exceeded LD50. On the other hand, with a cumulative dose below LD50 (and lower SNR), it was still possible to visualize the infection of E. coli by P1, showing the insertion of viral DNA within 3 s, with 5 nm resolution. PMID- 26811951 TI - A Modular Formal Total Synthesis of (+/-)-Cycloclavine. AB - Cycloclavine is a clavine-type Ergot alkaloid noteworthy for its unique pentacyclic skeleton featuring a 3-azabicyclo[3.1.0]hexane substructure. A short convergent route to the racemic alkaloid is described which comprises only eight linear steps and requires only four chromatographic purifications. The two key building blocks can be prepared in high yield from commercially available starting materials. Two consecutive coupling reactions, namely a selective alkylation of a dienolate and a Heck reaction, are the key steps of the reaction sequence. PMID- 26811952 TI - KIO3-Catalyzed Aerobic Cross-Coupling Reactions of Enaminones and Thiophenols: Synthesis of Polyfunctionalized Alkenes by Metal-Free C-H Sulfenylation. AB - The synthesis of polyfunctionalized aminothioalkenes has been realized via the direct C-H sulfenylation of enaminones and analogous enamines. These cross coupling reactions have been achieved by simple KIO3 catalysis under aerobic conditions without employing any transition metal catalyst or additional oxidant. The employment of bio-based green solvent ethyl lactate as the reaction medium constitutes another sustainable feature of the present work. PMID- 26811953 TI - Diagnostic Algorithm for Residual Pain After Total Knee Arthroplasty. AB - Although total knee arthroplasty is a successful and cost-effective procedure, patient dissatisfaction remains as high as 50%. Postoperative residual knee pain after total knee arthroplasty, with or without crepitation, is a major factor that contributes to patient dissatisfaction. The most common location for residual pain after total knee arthroplasty is anteriorly. Because residual pain has been associated with an un-resurfaced patella, this review includes only registry data and total knee arthroplasty with patella replacement. Some suggest that the pathogenesis of residual knee pain may be related to mechanical stimuli that activate free nerve endings around the patellofemoral joint. Various etiologies have been implicated in residual pain, including (1) low-grade infection, (2) midflexion instability, and (3) component malalignment with patellar maltracking. Less common causes include (4) crepitation and patellar clunk syndrome; (5) patellofemoral symptoms, including overstuffing and avascular necrosis of the patella; (6) early aseptic loosening; (7) hypersensitivity to metal or cement; (8) complex regional pain syndrome; and (9) pseudoaneurysm. Because all of these conditions can lead to residual pain, identifying the etiology can be a difficult diagnostic challenge. Often, patients with persistent pain and normal findings on radiographs and laboratory workup may benefit from a diagnostic injection or further imaging. However, up to 10% to 15% of patients with residual pain may have unexplained pain. This literature review summarizes the findings on the causes of residual pain and presents a diagnostic algorithm to facilitate an accurate diagnosis for residual pain after total knee arthroplasty. PMID- 26811954 TI - Patient Anxiety, Pain, and Satisfaction With Image-Guided Needle Biopsy. AB - Image-guided percutaneous needle biopsy has become the preferred diagnostic modality for bone and soft tissue tumors. However, to the authors' knowledge, the levels of patient anxiety, pain, and satisfaction before and after the procedure have not been studied. Sixty-five patients undergoing image-guided needle biopsy of a possible bone or soft tissue tumor were prospectively surveyed to quantify preprocedure and postprocedure levels of anxiety and pain and to determine demographic and clinical correlates of anxiety, pain, and satisfaction. Anxiety was measured with the Spielberger State-Trait Anxiety Inventory, pain was measured with a visual analog scale, and satisfaction was measured by patient willingness to repeat the procedure if necessary. Statistical analysis was performed with Student's t test, Fisher's exact test, and linear regression analysis. Compared with preprocedure values, trait anxiety (defined as the underlying level of anxiety, P<.0011), state anxiety (defined as the current level of situational anxiety, P<.001), and pain (P<.05) decreased significantly postprocedure. The relationship between changes in pain and state anxiety was significant (r=0.31, P=.014), whereas no relationship was seen between changes in pain and trait anxiety (r=0.13, P=.28). Patients who were somewhat satisfied with the procedure reported higher levels of postprocedure pain than those who were completely satisfied (5.24+/-2.19 cm vs 1.70+/-2.08 cm, respectively; P<.001). In other words, lower levels of experienced pain correlated with patient satisfaction. Older age was inversely correlated with postprocedure pain (r=0.41, P=.001), and there was a trend toward increasing dissatisfaction among younger patients. PMID- 26811955 TI - Computer-Simulated Arthroscopic Knee Surgery: Effects of Distraction on Resident Performance. AB - Orthopedic surgeons cite "full focus" and "distraction control" as important factors for achieving excellent outcomes. Surgical simulation is a safe and cost effective way for residents to practice surgical skills, and it is a suitable tool to study the effects of distraction on resident surgical performance. This study investigated the effects of distraction on arthroscopic knee simulator performance among residents at various levels of experience. The authors hypothesized that environmental distractions would negatively affect performance. Twenty-five orthopedic surgery residents performed a diagnostic knee arthroscopy computer simulation according to a checklist of structures to identify and tasks to complete. Participants were evaluated on arthroscopy time, number of chondral injuries, instances of looking down at their hands, and completion of checklist items. Residents repeated this task at least 2 weeks later while simultaneously answering distracting questions. During distracted simulation, the residents had significantly fewer completed checklist items (P<.02) compared with the initial simulation. Senior residents completed the initial simulation in less time (P<.001), with fewer chondral injuries (P<.005) and fewer instances of looking down at their hands (P<.012), compared with junior residents. Senior residents also completed 97% of the diagnostic checklist, whereas junior residents completed 89% (P<.019). During distracted simulation, senior residents continued to complete tasks more quickly (P<.006) and with fewer instances of looking down at their hands (P<.042). Residents at all levels appear to be susceptible to the detrimental effects of distraction when performing arthroscopic simulation. Addressing even straightforward questions intraoperatively may affect surgeon performance. PMID- 26811956 TI - Effect of Microfracture on Meniscal Tear Healing in a Goat (Capra hircus) Model. AB - Meniscal injuries are an extremely common cause of knee pain. Meniscal repairs performed with concomitant anterior cruciate ligament reconstruction appear to heal at a higher rate than meniscal repairs performed in isolation. This may be due in part to the release of marrow elements into the knee and the time of meniscal repair. In cases of isolated meniscal repair, some orthopedic surgeons use microfracture to release marrow elements into the joint as an adjunct to enhance meniscal healing. This study evaluated rates of meniscal tear healing with or without the performance of microfracture in a goat (Capra hircus) model. Forty castrated young adult male goats underwent either a horizontal or a longitudinal 1.0-cm meniscal tear with or without microfracture. All procedures were performed open, in a bloodless field. Meniscal tears were created in the peripheral half of the body of the medial meniscus. The goats were euthanized at 6 months, and meniscal tears were analyzed and classified as complete healing, partial healing, or no healing by direct visualization. A probe was used as an aid to evaluate and classify the meniscal tears. Twenty (87%) of 23 goat meniscal tears showed at least partial healing when performed with concomitant microfracture. Only 5 (29%) of 17 menisci showed any healing in goats that did not receive microfracture. This difference in healing rates was statistically significant (P<.001). Fifteen (65%) meniscal tears accomplished with microfracture were completely healed, whereas only 2 (12%) menisci showed complete healing without microfracture (P<.001). The results of this study suggest that the release of bone marrow elements into the knee by microfracture improves meniscal healing rates. PMID- 26811957 TI - Reverse Total Shoulder Arthroplasty and Work-Related Outcomes. AB - The average retirement age is increasing, and the indications for reverse total shoulder arthroplasty (RTSA) are being broadened. The goal of the current study was to determine objective findings for rate of return to work and time to return to work after RTSA. The authors performed retrospective data collection for consecutive patients who underwent RTSA at their institution between 2007 and 2013. All patients were asked to complete a questionnaire about their work history and their ability to participate in work-related activities. A total of 40 patients reported working before surgery. Average patient age was 74.7 years (range, 56-82 years). Average follow-up was 2.6 years (range, 1-4.7 years). Average American Shoulder and Elbow Surgeons score improved from 34.0 to 81.7 (P<.001). Average visual analog scale pain score decreased from 6.5 to 0.7 (P<.001). Most patients (65.4%) classified their job as sedentary, 34.6% classified their job as light work, and no patients classified their job as heavy work. Of patients who worked preoperatively, 65% (n=26) returned to work after RTSA. Only a previous diagnosis of heart disease affected return to work (P=.04). Overall, average time to return to work was 2.3 months (range, 0.5-11 months). Patients with sedentary jobs returned to work more quickly (1.4 months) than those with light work (4.0 months). A total of 96.2% of patients reported good to excellent surgical outcomes. Of patients who worked before RTSA, 65% were still working at final follow-up. Only 5% of patients retired for reasons attributed to the operated shoulder. On average, patients returned to work less than 3 months after surgery. PMID- 26811958 TI - Locked Superior Patellar Dislocation. AB - Superior dislocation of the patella is a rare cause of knee locking, with fewer than 20 cases reported in the English literature. The vast majority of traumatic or even atraumatic knee locking cases are due to such varied conditions as meniscal tears, osteochondral lesions, osteoarthritis, and ligamentous tears. A careful examination with proper radiographic imaging must be undertaken to properly evaluate patients who present with a locked knee, as they may have interdigitating patellofemoral osteophytes. An unusual case of a locked knee secondary to interlocking osteophytes between the femoral condyle and the inferior pole of the patella without a history of trauma is presented. The authors show how local sedation and gentle reduction are usually sufficient treatment, and that the vast majority of patients with this injury quickly return to their baseline functional level without the need for general sedation or surgical treatment. PMID- 26811959 TI - Long-term Results of a First-Generation Annealed Highly Cross-Linked Polyethylene in Young, Active Patients. AB - The survivorship of total hip arthroplasty in younger patients is dependent on the wear characteristics of the bearing surfaces. Long-term results with conventional polyethylene in young patients show a high failure rate. This study assessed the long-term results of a first-generation annealed highly cross-linked polyethylene (HCLPE) in uncemented total hip arthroplasty in young, active patients. Between 1999 and 2003, 112 total hip arthroplasty procedures performed in 91 patients with an average University of California Los Angeles activity score of 8 and mean age of 53 years (range, 24-65 years) were included from a prospective database. In all patients, a 28-mm metal femoral head on annealed HCLPE (Crossfire; Stryker, Mahwah, New Jersey) was used. At minimum 10-year follow-up (11.5+/-0.94 years), Kaplan-Meier survivorship was 97% for all failures (1 periprosthetic infection and 1 late dislocation) and 100% for mechanical failure (no revisions for osteolysis or loosening). This study showed low revision rates for wear-related failure and superior survivorship in young, active patients. Oxidation causing failure of the locking mechanism has not been a problem with Crossfire for up to 10 years. PMID- 26811960 TI - Assessment of the energetic performances of various ZIFs with SOD or RHO topology using high pressure water intrusion-extrusion experiments. AB - The energetic performances of seven SOD or RHO-topology ZIFs, with zinc or cobalt metal cation (ZIF-8, ZIF-90, Zn(dcim)2-SALE, ZIF-67, ZIF-7, ZIF-71, ZIF-11) were evaluated using water intrusion-extrusion under high pressure. The relationship between the structural parameters (in particular the pore system SOD or RHO, the type of linker, the metal cation nature) and the intrusion pressure was studied to better understand the mechanism of water intrusion and the energetic behaviour for a given ZIF crystal type. "ZIF-8-water", "ZIF-67-water" and "ZIF-71-water" systems display a shock-absorber behaviour. A very important hysteresis for ZIF 71 and a slight difference between the first intrusion-extrusion cycle and the following ones for ZIF-67 were observed. ZIF-8 (SOD) with zinc cation and ZIF-67 (SOD) with cobalt cation display similar intrusion pressures. For ZIF-71 (RHO) material, the stored energy is more than doubled compared to ZIF-8 and ZIF-67 (SOD). This might be related to the topology. No water intrusion was observed after three water intrusion-extrusion cycles, for the ZIF-90 (SOD), Zn(dcim)2 SALE (SOD), ZIF-7 (SOD) and ZIF-11 (RHO) materials. This is explained in term of hydrophilic feature as well as topology and linker effects. PMID- 26811961 TI - Staircase patterns of nuclear fluxes during coherent tunneling in excited doublets of symmetric double well potentials. AB - Tunneling isomerization of molecules with symmetric double well potentials are associated with periodic nuclear fluxes, from the reactant R to the product P and back to R. Halfway between R and P the fluxes achieve their maximum values at the potential barrier. For molecules in the lowest tunneling doublet (v = 0) the rises and falls to and from the maximum values are approximately bell-shaped. Upon excitation to higher tunneling doublets v = 1, 2, etc., however, this shape is replaced by symmetric "staircase patterns" of the fluxes, with v + 1 stepping up and down in the domains of R and P, respectively. The quantum derivation of the phenomenon is universal. It is demonstrated here for a simple model of nuclear fluxes during tunneling isomerization of ammonia along the umbrella inversion mode, with application to separation of isotopomers. PMID- 26811963 TI - A multiple covalent crosslinked soft hydrogel for bioseparation. AB - A multiple covalent crosslinked gel of poly(acrylamide-acrylic acid) was synthesized by using acrylic acid and acrylamide both as a comonomer and as a covalent crosslinker. The resultant gel showed a high crosslinking degree, tight micropores, but similar softness and marked separation capacity, in contrast to traditional polyacrylamide gels. The gel might serve as a novel matrix in bioseparation. PMID- 26811962 TI - Pt74Ag26 nanoparticle-decorated ultrathin MoS2 nanosheets as novel peroxidase mimics for highly selective colorimetric detection of H2O2 and glucose. AB - To extend the functionalities of two-dimensional graphene-like layered compounds as versatile materials, the modification of transition metal dichalcogenide nanosheets such as MoS2 with metal nanoparticles is of great and widespread interest. However, few studies are available on the preparation of bimetallic nanoparticles supported on MoS2. Herein, a facile and efficient method to synthesize MoS2-PtAg nanohybrids by decorating ultrathin MoS2 nanosheets with octahedral Pt74Ag26 alloy nanoparticles has been reported. The as-prepared MoS2 Pt74Ag26 nanohybrids were investigated as novel peroxidase mimics to catalyze the oxidation of classical peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2, producing a blue colored reaction and exhibiting typical Michaelis-Menten kinetics. MoS2-Pt74Ag26 has a higher affinity for H2O2 than horseradish peroxidase (HRP) and a higher vmax value with TMB as the substrate than MoS2. The improved catalytic activity of hybrids for colorimetric reactions could be attributed to the synergistic effects of octahedral Pt74Ag26 nanoparticles and ultrathin MoS2 nanosheets as supports. Meanwhile, the generation of active oxygen species (OH) by H2O2 decomposition with MoS2-Pt74Ag26 was responsible for the oxidation of TMB. On the basis of these findings, a colorimetric method based on MoS2-Pt74Ag26 nanohybrids that is highly sensitive and selective was developed for glucose detection. Lower values of the limit of detection (LOD) were obtained, which is more sensitive than MoS2 nanosheets. PMID- 26811965 TI - Flexoelectricity, incommensurate phases and the Lifshitz point. AB - The solutions for the minimizers of the energy density f (q, p) = Aq2 + Bq4 + p2 + gA,B + beta(q'p - p'q)+ |q'|2 +kappa|p'|2] describe the flexoelectric effect with a flexoelectric coupling coefficient beta. The order parameters q and p can be visualized as strain and polarisation, respectively. The parameter kappa denotes the ratio of intrinsic length scales for q and p. We show that the structural ground-states include 3 phases, namely the paraelastic state q = p = 0, the ferroelastic state where polarization exists inside and near twin boundaries, and the incommensurate (modulated) phases with a very rich array of structural modulations ranging from nearly pure sine waves to kink arrays and ripple states. The phases coincide in the multicritical Lifshitz point. Linear flexoelectricity p~q' is encountered only approximately inside the ferroelastic phase and near the phase boundary between the paraelastic phase and the incommensurate phase. The relationship between the polarisation and the strain gradient is highly non-linear in all other states. The spatial profiles and energy distributions are discussed in detail. PMID- 26811964 TI - The Biochemical Basis of Vitamin A3 Production in Arthropod Vision. AB - Metazoan photochemistry involves cis-trans isomerization of a retinylidene chromophore bound to G protein coupled receptors. Successful production of chromophores is critical for photoreceptor function and survival. For chromophore production, animals have to choose from more than 600 naturally occurring carotenoids and process them by oxidative cleavage and geometric isomerization of double bonds. Vertebrates employ three carotenoid cleavage oxygenases to tailor the carotenoid precursor in the synthesis of 11-cis-retinal (vitamin A1). Lepidoptera (butterfly and moth) possess only one such enzyme, NinaB, which faces the challenge to catalyze these reactions in unison to produce 11-cis-3-hydroxy retinal (vitamin A3). We here showed that key to this multitasking is a bipartite substrate recognition site that conveys regio- and stereoselectivity for double bond processing. One side performed the specific C11, C12 cis-isomerization and preferentially binds 3-OH-beta-ionone rings sites. The other side maintained a trans configuration in the resulting product and preferentially binds noncanonical ionone ring sites. Concurrent binding of carotenoids containing two cyclohexyl rings to both domains is required for specific oxidative cleavage at position C15, C15' of the substrate. The unique reaction sequence follows a dioxygenase mechanism with a carbocation/radical intermediate. This ingenious quality control system guarantees 11-cis-3-hydroxy-retinal production, the essential retinoid for insect (vitamin A3) vision. PMID- 26811966 TI - DNA Binding and Photocleavage Properties, Cellular Uptake and Localization, and in-Vitro Cytotoxicity of Dinuclear Ruthenium(II) Complexes with Varying Lengths in Bridging Alkyl Linkers. AB - Two new dinuclear Ru(II) polypyridyl complexes containing three and ten methylene chains in their bridging linkers are synthesized and characterized. Their calf thymus DNA-binding and plasmid DNA photocleavage behaviors are comparatively studied with a previously reported, six-methylene-containing analog by absorption and luminescence spectroscopy, steady-state emission quenching by [Fe(CN)6](4-), DNA competitive binding with ethidium bromide, DNA viscosity measurements, DNA thermal denaturation, and agarose gel electrophoresis analyses. Theoretical calculations applying the density functional theory (DFT) method for the three complexes are also performed to understand experimentally observed DNA binding properties. The results show that the two complexes partially intercalate between the base pairs of DNA. Cellular uptake and colocalization studies have demonstrated that the complexes could enter HeLa cells efficiently and localize within lysosomes. The in-vitro antitumor activity against HeLa and MCF-7 tumor cells of the complexes are studied by MTT cytotoxic analysis. A new method, high content analysis (HCA), is also used to assess cytotoxicity, apoptosis and cell cycle arrest of the three complexes. The results show that the lengths of the alkyl linkers could effectively tune their biological properties and that HCA is suitable for rapidly identifying cytotoxicity and can be substituted for MTT assays to evaluate the cell cytotoxicity of chemotherapeutic agents. PMID- 26811967 TI - Hospital Adoption of Health Information Technology to Support Public Health Infrastructure. AB - CONTEXT: Health information technology (IT) has the potential to improve the nation's public health infrastructure. In support of this belief, meaningful use incentives include criteria for hospitals to electronically report to immunization registries, as well as to public health agencies for reportable laboratory results and syndromic surveillance. Electronic reporting can facilitate faster and more appropriate public health response. However, it remains unclear the extent that hospitals have adopted IT for public health efforts. OBJECTIVE: To examine hospital adoption of IT for public health and to compare hospitals capable of using and not using public health IT. DESIGN: Cross sectional design with data from the 2012 American Hospital Association annual survey matched with data from the 2013 American Hospital Association Information Technology Supplement. Multivariate logistic regression was used to compare hospital characteristics. Inverse probability weights were applied to adjust for selection bias because of survey nonresponse. PARTICIPANTS: All acute care general hospitals in the United States that matched across the surveys and had complete data available were included in the analytic sample. MAIN OUTCOME MEASURES: Three separate outcome measures were used: whether the hospital could electronically report to immunization registries, whether the hospital could send electronic laboratory results, and whether the hospital can participate in syndromic surveillance. RESULTS: A total of 2841 hospitals met the inclusion criteria. Weighted results show that of these hospitals, 62.7% can electronically submit to immunization registries, 56.6% can electronically report laboratory results, and 54.4% can electronically report syndromic surveillance. Adjusted and weighted results from the multivariate analyses show that small, rural hospitals and hospitals without electronic health record systems lag in the adoption of public health IT capabilities. CONCLUSION: While a majority of hospitals are using public health IT, the infrastructure still has significant room for growth. Differences in hospitals' adoption of public health IT may exacerbate existing health disparities. PMID- 26811968 TI - Randomized Controlled Trial of Hospital-Based Hygiene and Water Treatment Intervention (CHoBI7) to Reduce Cholera. AB - The risk for cholera infection is >100 times higher for household contacts of cholera patients during the week after the index patient seeks hospital care than it is for the general population. To initiate a standard of care for this high risk population, we developed Cholera-Hospital-Based-Intervention-for-7-Days (CHoBI7), which promotes hand washing with soap and treatment of water. To test CHoBI7, we conducted a randomized controlled trial among 219 intervention household contacts of 82 cholera patients and 220 control contacts of 83 cholera patients in Dhaka, Bangladesh, during 2013-2014. Intervention contacts had significantly fewer symptomatic Vibrio cholerae infections than did control contacts and 47% fewer overall V. cholerae infections. Intervention households had no stored drinking water with V. cholerae and 14 times higher odds of hand washing with soap at key events during structured observation on surveillance days 5, 6, or 7. CHoBI7 presents a promising approach for controlling cholera among highly susceptible household contacts of cholera patients. PMID- 26811969 TI - Molecular Composition and Volatility of Organic Aerosol in the Southeastern U.S.: Implications for IEPOX Derived SOA. AB - We present measurements as part of the Southern Oxidant and Aerosol Study (SOAS) during which atmospheric aerosol particles were comprehensively characterized. We present results utilizing a Filter Inlet for Gases and AEROsol coupled to a chemical ionization mass spectrometer (CIMS). We focus on the volatility and composition of isoprene derived organic aerosol tracers and of the bulk organic aerosol. By utilizing the online volatility and molecular composition information provided by the FIGAERO-CIMS, we show that the vast majority of commonly reported molecular tracers of isoprene epoxydiol (IEPOX) derived secondary organic aerosol (SOA) is derived from thermal decomposition of accretion products or other low volatility organics having effective saturation vapor concentrations <10(-3) MUg m(-3). In addition, while accounting for up to 30% of total submicrometer organic aerosol mass, the IEPOX-derived SOA has a higher volatility than the remaining bulk. That IEPOX-SOA, and more generally bulk organic aerosol in the Southeastern U.S. is comprised of effectively nonvolatile material has important implications for modeling SOA derived from isoprene, and for mechanistic interpretations of molecular tracer measurements. Our results show that partitioning theory performs well for 2-methyltetrols, once accretion product decomposition is taken into account. No significant partitioning delays due to aerosol phase or viscosity are observed, and no partitioning to particle-phase water or other unexplained mechanisms are needed to explain our results. PMID- 26811970 TI - Reply to: Importance of immunisation of elderly subjects before immunosuppressive treatment. PMID- 26811971 TI - Malaria in French Guiana Linked to Illegal Gold Mining. PMID- 26811972 TI - Modelling the Tox21 10 K chemical profiles for in vivo toxicity prediction and mechanism characterization. AB - Target-specific, mechanism-oriented in vitro assays post a promising alternative to traditional animal toxicology studies. Here we report the first comprehensive analysis of the Tox21 effort, a large-scale in vitro toxicity screening of chemicals. We test ~ 10,000 chemicals in triplicates at 15 concentrations against a panel of nuclear receptor and stress response pathway assays, producing more than 50 million data points. Compound clustering by structure similarity and activity profile similarity across the assays reveals structure-activity relationships that are useful for the generation of mechanistic hypotheses. We apply structural information and activity data to build predictive models for 72 in vivo toxicity end points using a cluster-based approach. Models based on in vitro assay data perform better in predicting human toxicity end points than animal toxicity, while a combination of structural and activity data results in better models than using structure or activity data alone. Our results suggest that in vitro activity profiles can be applied as signatures of compound mechanism of toxicity and used in prioritization for more in-depth toxicological testing. PMID- 26811974 TI - Evaluation of adjuvant carboplatin chemotherapy in the management of surgically excised anal sac apocrine gland adenocarcinoma in dogs. AB - There is no widely accepted standard of care for canine anal sac apocrine gland adenocarcinoma (ASAGAC). Surgery alone is inadequate in many cases, but the benefit of adjuvant chemotherapy is not well established. The primary objective of this retrospective study was to evaluate the role of carboplatin chemotherapy in the post-operative management of ASAGAC. Seventy-four dogs with naturally occurring ASAGAC underwent surgery. Forty-four dogs received adjuvant carboplatin and 30 did not. Median overall survival (OS) was 703 days. Median time to progression (TTP) was 384 days. Only primary tumour size and lymph node metastasis at diagnosis significantly impacted the outcome. Differences in OS and TTP, between the dogs that received adjuvant carboplatin and those that did not, failed to reach statistical significance. Treatment of progressive disease, whilst not limited to chemotherapy, significantly prolonged the survival. This study shows that adjuvant carboplatin chemotherapy is well tolerated and may have a role in the management of dogs with ASAGAC. PMID- 26811973 TI - Capturing fast relaxing spins with SWIFT adiabatic rotating frame spin-lattice relaxation (T1rho) mapping. AB - Rotating frame spin-lattice relaxation, with the characteristic time constant T1rho, provides a means to access motion-restricted (slow) spin dynamics in MRI. As a result of their restricted motion, these spins are sometimes characterized by a short transverse relaxation time constant T2 and thus can be difficult to detect directly with conventional image acquisition techniques. Here, we introduce an approach for three-dimensional adiabatic T1rho mapping based on a magnetization-prepared sweep imaging with Fourier transformation (MP-SWIFT) sequence, which captures signal from almost all water spin populations, including the extremely fast relaxing pool. A semi-analytical procedure for T1rho mapping is described. Experiments on phantoms and musculoskeletal tissue specimens (tendon, articular and epiphyseal cartilages) were performed at 9.4 T for both the MP-SWIFT and fast spin echo (FSE) read outs. In the phantom with liquids having fast molecular tumbling and a single-valued T1rho time constant, the measured T1rho values obtained with MP-SWIFT and FSE were similar. Conversely, in normal musculoskeletal tissues, T1rho values measured with MP-SWIFT were much shorter than the values obtained with FSE. Studies of biological tissue specimens demonstrated that T1rho-weighted SWIFT provides higher contrast between normal and diseased tissues relative to conventional acquisitions. Adiabatic T1rho mapping with SWIFT readout captures contributions from the otherwise undetected fast relaxing spins, allowing more informative T1rho measurements of normal and diseased states. PMID- 26811979 TI - Dynamic Chirality Control of tropos DPCB-digold Skeleton by Chiral Binaphthyldicarboxylate. AB - The planar 3,4-diphosphinidenecyclobutene (DPCB) can be remarkably twisted into a C2 -type helical structure by dual coordination of a AuCl moiety. A prompt chirality control of the twisted DPCB skeleton ligated by the digold units affords the enantiopure structure by exchanging the chloride ligands for chiral [1,1'-binaphthalene]-2,2'-dicarboxylate. The chirality of the diaurated 2,2' bis(diphenylphosphanyl)-1,1'-biphenyl (BIPHEP) system can be controlled prior to that of DPCB. Mixing of a DPCB-bis(chlorogold) complex with the chiral silver salt dynamically leads to a single diastereomer, which was characterized by the (31) P NMR spectrum and the CD couplet patterns in the visible (DPCB) area. The absolute configuration of the singly induced helical structure was assigned by the theoretical CD spectra determined by TD-DFT calculations. Intramolecular alkoxycyclization of hexa-4,5-dien-1-ol catalyzed by the asymmetric DPCB-digold structure were also attempted. PMID- 26811980 TI - Ebola and Its Control in Liberia, 2014-2015. AB - The severe epidemic of Ebola virus disease in Liberia started in March 2014. On May 9, 2015, the World Health Organization declared Liberia free of Ebola, 42 days after safe burial of the last known case-patient. However, another 6 cases occurred during June-July; on September 3, 2015, the country was again declared free of Ebola. Liberia had by then reported 10,672 cases of Ebola and 4,808 deaths, 37.0% and 42.6%, respectively, of the 28,103 cases and 11,290 deaths reported from the 3 countries that were heavily affected at that time. Essential components of the response included government leadership and sense of urgency, coordinated international assistance, sound technical work, flexibility guided by epidemiologic data, transparency and effective communication, and efforts by communities themselves. Priorities after the epidemic include surveillance in case of resurgence, restoration of health services, infection control in healthcare settings, and strengthening of basic public health systems. PMID- 26811981 TI - Hepatitis B virus causes mixed cryoglobulinaemia by driving clonal expansion of innate B-cells producing a VH1-69-encoded antibody. AB - OBJECTIVES: To investigate the expression of a VH1-69-encoded idiotype, and the phenotypic and functional features of monoclonal B-cells from patients with type II mixed cryoglobulinaemia (MC) secondary to chronic hepatitis B virus (HBV) infection. METHODS: B-cell immunophenotype and expression of a VH1-69-encoded idiotype were investigated by flow cytometry. B-cell proliferative responses to stimuli were investigated by the CFSE dilution assay. RESULTS: Two out of five patients with chronic HBV studied had massive monoclonal expansion of VH1-69 expressing B-cells. These cells had the peculiar CD21(low) phenotype and low responsiveness to stimuli typical of the VH1-69-expressing B-cells commonly expanded in MC secondary to hepatitis C virus (HCV) infection. In both patients, anti-HBV therapy led to the regression of MC and of VH1-69+ B-cell expansion. CONCLUSIONS: VH1-69-encoded antibodies are known to preferentially recognise a variety of viral proteins including HCV E2, influenza A virus haemagglutinin and HIV gp41/gp120, and may serve as innate first line antiviral defense. Thus, like HCV, HBV may cause MC by protracted antigenic stimulation of VH1-69-expressing B cells. PMID- 26811982 TI - Dynamic Loading and Unloading of Proteins in Polymeric Stomatocytes: Formation of an Enzyme-Loaded Supramolecular Nanomotor. AB - Self-powered artificial nanomotors are currently attracting increased interest as mimics of biological motors but also as potential components of nanomachinery, robotics, and sensing devices. We have recently described the controlled shape transformation of polymersomes into bowl-shaped stomatocytes and the assembly of platinum-driven nanomotors. However, the platinum encapsulation inside the structures was low; only 50% of the structures contained the catalyst and required both high fuel concentrations for the propelling of the nanomotors and harsh conditions for the shape transformation. Application of the nanomotors in a biological setting requires the nanomotors to be efficiently propelled by a naturally available energy source and at biological relevant concentrations. Here we report a strategy for enzyme entrapment and nanomotor assembly via controlled and reversible folding of polymersomes into stomatocytes under mild conditions, allowing the encapsulation of the proteins inside the stomach with almost 100% efficiency and retention of activity. The resulting enzyme-driven nanomotors are capable of propelling these structures at low fuel concentrations (hydrogen peroxide or glucose) via a one-enzyme or two-enzyme system. The confinement of the enzymes inside the stomach does not hinder their activity and in fact facilitates the transfer of the substrates, while protecting them from the deactivating influences of the media. This is particularly important for future applications of nanomotors in biological settings especially for systems where fast autonomous movement occurs at physiological concentrations of fuel. PMID- 26811983 TI - Impacts of Heterogeneous TiO2 and Al2O3 Composite Mesoporous Scaffold on Formamidinium Lead Trihalide Perovskite Solar Cells. AB - Heterogeneous TiO2 and Al2O3 composites were employed as a mesoporous scaffold in formamidinium lead trihalide (FAPbI3-xClx)-based perovskite solar cells to modify surface properties of a mesoporous layer. It was found that the quality and morphology of the perovskite film were strongly affected by the TiO2/Al2O3 ratio in the mesoporous film. The conversion efficiency of the perovskite solar cell was improved by using a composite of TiO2 and Al2O3 in comparison with TiO2- and Al2O3-based cells, yielding 11.0% for a cell with a 7:3 TiO2/Al2O3 composite. Our investigation shows a change of electron transport path depending on a composition ratio of insulating Al2O3 to n-type semiconducting TiO2 in a mesoporous layer. PMID- 26811984 TI - Ebola Virus Persistence in Semen Ex Vivo. AB - On March 20, 2015, a case of Ebola virus disease was identified in Liberia that most likely was transmitted through sexual contact. We assessed the efficiency of detecting Ebola virus in semen samples by molecular diagnostics and the stability of Ebola virus in ex vivo semen under simulated tropical conditions. PMID- 26811985 TI - High Prevalence of Borrelia miyamotoi among Adult Blacklegged Ticks from White Tailed Deer. AB - We compared the prevalence of Borrelia miyamotoi infection in questing and deer associated adult Ixodes scapularis ticks in Wisconsin, USA. Prevalence among deer associated ticks (4.5% overall, 7.1% in females) was significantly higher than among questing ticks (1.0% overall, 0.6% in females). Deer may be a sylvatic reservoir for this newly recognized zoonotic pathogen. PMID- 26811986 TI - Metal-Polysaccharide Interplay: Beyond Metal Immobilization, Graphenization Induced-Anisotropic Growth. AB - Such sweet support: Metal-polysaccharide interplay affords, after pyrolytic transformation, highly active catalysts based on anisotropically oriented nanoparticles supported on graphene sheets. PMID- 26811987 TI - Dehydrohalogenation and Dehydration Reactions of i-C3H7Br and i-C3H7OH by Sodium Ions Studied by Guided Ion Beam Techniques and Quantum Chemical Methods. AB - Dehydrohalogenation and dehydration reactions of gas-phase i-C3H7Br and i-C3H7OH molecules induced by collision with Na(+), all participants being in their electronic ground state, were studied experimentally in our laboratory using a radiofrequency-guided ion beam apparatus and covering the 0.10-10.00 eV center of mass (CM) energy range. In Na(+) + i-C3H7Br collisions the formation of [C3H6 Na](+) and [HBr-Na](+) by dehydrohalogenation was observed and quantified, as well as that of the ion-molecule adduct [Na-i-C3H7Br](+) together with its decomposition products C3H7(+) and NaBr. In Na(+) + i-C3H7OH collisions the dehydration product [H2O-Na](+) was also found, while [C3H6-Na](+) was hardly detected. Moreover, the [Na-i-C3H7OH](+) adduct formation as well as its decomposition into C3H7(+) and NaOH were also quantified. For all these processes, absolute reaction cross sections were measured as a function of the CM collision energy. From measured excitation functions, rate constants for the formation of [C3H6-Na](+), [HBr-Na](+), and [H2O-Na](+) at 303 K were obtained. Complementing the experiments, exhaustive ab initio structure calculations at the MP2 level of theory were performed, giving information on the most relevant features of the potential energy surfaces (PESs) where the dehydrohalogenation, dehydration, and decomposition reactions take place adiabatically for both collision systems. On these PESs different stationary points associated with potential energy minima and transition state barriers were characterized, and their connectivity was ensured using the intrinsic-reaction-coordinate method. The main topology features of the ab initio calculated PESs allowed a qualitative interpretation of the experimental data also exposing the role of the sodium ion as a catalyst in elimination reactions. PMID- 26811988 TI - Surface Morphology of Vapor-Deposited Chitosan: Evidence of Solid-State Dewetting during the Formation of Biopolymer Films. AB - Chitosan is a useful and versatile biopolymer with several industrial and biological applications. Whereas its physical and physicochemical bulk properties have been explored quite intensively in the past, there is a lack of studies regarding the morphology and growth mechanisms of thin films of this biopolymer. Of particular interest for applications in bionanotechnology are ultrathin films with thicknesses under 500 A. Here, we present a study of thin chitosan films prepared in a dry process using physical vapor deposition and in situ ellipsometric monitoring. The prepared films were analyzed with atomic force microscopy in order to correlate surface morphology with evaporation parameters. We find that the surface morphology of our final thin films depends on both the optical thickness, i.e., measured with ellipsometry, and the deposition rate. Our work shows that ultrathin biopolymer films can undergo dewetting during film formation, even in the absence of solvents and thermal annealing. PMID- 26811989 TI - Visualizing Nanoscale Distribution of Corrosion Cells by Open-Loop Electric Potential Microscopy. AB - Corrosion is a traditional problem but still one of the most serious problems in industry. To reduce the huge economic loss caused by corrosion, tremendous effort has been made to understand, predict and prevent it. Corrosion phenomena are generally explained by the formation of corrosion cells at a metal-electrolyte interface. However, experimental verification of their nanoscale distribution has been a major challenge owing to the lack of a method able to visualize the local potential distribution in an electrolytic solution. In this study, we have investigated the nanoscale corrosion behavior of Cu fine wires and a duplex stainless steel by in situ imaging of local corrosion cells by open-loop electric potential microscopy (OL-EPM). For both materials, potential images obtained by OL-EPM show nanoscale contrasts, where areas of higher and lower potential correspond to anodic areas (i.e., corrosion sites) and cathodic areas, respectively. This imaging capability allows us to investigate the real-time transition of local corrosion sites even when surface structures show little change. This is particularly useful for investigating reactions under surface oxide layers or highly corrosion-resistant materials as demonstrated here. The proposed technique should be applicable to the study of other redox reactions on a battery electrode or a catalytic material. The results presented here open up such future applications of OL-EPM in nanoscale electrochemistry. PMID- 26811990 TI - Multicomponent Strategy for the Synthesis of Prostaglandin E2 Methyl Ester under Anion Relay Chelation Control. AB - Starting with four components, the enantioselective synthesis of prostaglandin E2 methyl ester has been achieved through a highly stereoselective heteroatom directed conjugate addition reaction and cyclopentanone ring cyclization as the key steps. This asymmetric strategy includes (i) an asymmetric Reformatsky reaction; (ii) conjugate addition of a chiral vinyllithium reagent; (iii) cyclization to form a sulfonylated cyclopentanone in one-pot; followed by (iv) allylation of the side chain. Four carbon-carbon bond-forming processes and three stereogenic centers were established, with the steps from (ii) to (iii) being achieved in a one-pot process. PMID- 26811992 TI - Atypical ploidy cycles, Spo11, and the evolution of meiosis. AB - The Spo11 protein induces DNA double strand breaks before the first division of meiosis, enabling the formation of the chiasmata that physically link homologous chromosomes as they align. Spo11 is an ancient and well conserved protein, related in sequence and structure to a DNA topoisomerase subunit found in Archaea as well as a subset of eukaryotes. However the origins of its meiotic function are unclear. This review examines some apparent exceptions to the rule that Spo11 activity is specific to, and required for meiosis. Spo11 appears to function in the context of unusual forms of ploidy reduction in some protists and fungi. One lineage of amoebae, the dictyostelids, is thought to undergo meiosis during its sexual cycle despite having lost Spo11 entirely. Further experimental characterisation of these and other non-canonical ploidy cycling mechanisms may cast light of the evolution of meiosis. PMID- 26811991 TI - Total Synthesis of K777: Successful Application of Transition-Metal-Catalyzed Alkyne Hydrothiolation toward the Modular Synthesis of a Potent Cysteine Protease Inhibitor. AB - We report the total synthesis of K777 and a series of analogues via alkyne hydrothiolation catalyzed by Wilkinson's complex (ClRh(PPh3)3). The alkyne hydrothiolation reactions proceeded with excellent regio- and diastereoselectivity to generate the desired E-linear vinyl sulfides in high yield. The use of Ellman's auxiliary generates the requisite propargyl amines in excellent enantiomeric excess (ee) and obviates the use of L-homophenylalanine, an expensive unnatural amino acid. The vinyl sulfone derivatives exhibit a large difference in rate toward Michael addition. Kinetic data are consistent with rate limiting nucleophilic attack to generate the carbanion intermediate. PMID- 26811993 TI - Three-dimensional superhydrophobic copper 7,7,8,8-tetracyanoquinodimethane biointerfaces with the capability of high adhesion of osteoblasts. AB - A three-dimensional superhydrophobic copper 7,7,8,8-tetracyanoquinodimethane (CuTCNQ) nanowire array with the capability of high adhesion of osteoblasts was demonstrated. The CuTCNQ nanowire array was constructed by using a combined vapor deposition technique. The superhydrophobic nanowire array exhibited very high adhesion of osteoblasts, indicating that the CuTCNQ nanowire array was a good biointerface. PMID- 26811995 TI - Estimation of the minimum mRNA splicing error rate in vertebrates. AB - The majority of protein coding genes in vertebrates contain several introns that are removed by the mRNA splicing machinery. Errors during splicing can generate aberrant transcripts and degrade the transmission of genetic information thus contributing to genomic instability and disease. However, estimating the error rate of constitutive splicing is complicated by the process of alternative splicing which can generate multiple alternative transcripts per locus and is particularly active in humans. In order to estimate the error frequency of constitutive mRNA splicing and avoid bias by alternative splicing we have characterized the frequency of splice variants at three loci, HPRT, POLB, and TRPV1 in multiple tissues of six vertebrate species. Our analysis revealed that the frequency of splice variants varied widely among loci, tissues, and species. However, the lowest observed frequency is quite constant among loci and approximately 0.1% aberrant transcripts per intron. Arguably this reflects the "irreducible" error rate of splicing, which consists primarily of the combination of replication errors by RNA polymerase II in splice consensus sequences and spliceosome errors in correctly pairing exons. PMID- 26811996 TI - Structural biology of intramembrane proteases: mechanistic insights from rhomboid and S2P to gamma-secretase. AB - Intramembrane proteases catalyze hydrolysis of peptide bond within the lipid bilayer and play a key role in a variety of cellular processes. These membrane embedded enzymes comprise four major classes: rhomboid serine proteases, site-2 metalloproteases, Rce1-type glutamyl proteases, and aspartyl proteases exemplified by signal peptide peptidase and gamma-secretase. In the past several years, three-dimensional structures of representative members of these four classes of intramembrane protease have been reported at atomic resolutions, which reveal distinct protein folds and active site configurations. These structures, together with structure-guided biochemical analyses, shed light on the working mechanisms of water access and substrate entry. In this review, we discuss the shared as well as unique features of these intramembrane proteases, with a focus on presenilin-the catalytic component of gamma-secretase. PMID- 26811994 TI - XPC deficiency is related to APE1 and OGG1 expression and function. AB - Oxidative DNA damage is considered to be a major cause of neurodegeneration and internal tumors observed in syndromes that result from nucleotide excision repair (NER) deficiencies, such as Xeroderma Pigmentosum (XP) and Cockayne Syndrome (CS). Recent evidence has shown that NER aids in removing oxidized DNA damage and may interact with base excision repair (BER) enzymes. Here, we investigated APE1 and OGG1 expression, localization and activity after oxidative stress in XPC deficient cells. The endogenous APE1 and OGG1 mRNA levels were lower in XPC deficient fibroblasts. However, XPC-deficient cells did not show hypersensitivity to oxidative stress compared with NER-proficient cells. To confirm the impact of an XPC deficiency in regulating APE1 and OGG1 expression and activity, we established an XPC-complemented cell line. Although the XPC complementation was only partial and transient, the transfected cells exhibited greater OGG1 expression and activity compared with XPC-deficient cells. However, the APE1 expression and activity did not significantly change. Furthermore, we observed a physical interaction between the XPC and APE1 proteins. Together, the results indicate that the responses of XPC-deficient cells under oxidative stress may not only be associated with NER deficiency per se but may also include new XPC functions in regulating BER proteins. PMID- 26811997 TI - Preorganized tridentate analogues of mixed hydroxyoxime/carboxylate nickel extractants. AB - A series of 22 tridentate unsaturated mono-anionic ligands having the atom sequence Y-C[double bond, length as m-dash]C-N=CH-C=C-Z(-1), with Y = N, O, or S and Z = O or S, has been studied to establish whether this backbone could be used to develop strong solvent extractants for nickel(II) which will preferably also show a high selectivity over iron(III) in the pH-dependent process: 2LH(org) + NiSO4 ? [(L)2Ni]org + H2SO4. All are capable of forming octahedral [(L)2Ni] complexes with a mer-arrangement of the YNZ(-1) donor set. X-ray crystal structures of three salicylaldimine proligands derived from 3-bromo-5-t-butyl-2 hydroxybenzaldehyde show these to have pre-organised donor sets in which the three donors are held in an approximately orthogonal arrangement by intramolecular hydrogen bonds. The tautomers observed are dependent on the nature of the Y atom and the extent to which it is favourable for this to form a bonding interaction with the acidic hydrogen atom on the salicylaldimine unit. X-ray crystal structure determinations of seven of the [(L)2Ni] complexes show these to have significantly distorted octahedral coordination geometries which partly account for the proligands proving to be fairly weak Ni-extractants. DFT calculations show that extractant strength is dependent on a combination of the binding strength of the YNZ(-1) donor set to the nickel ion and on the ease of deprotonation of the extractant. On this basis 3-nitro-4-t-octyl-6-(quinolin-8 imino)phenol is predicted, and is found, to be the strongest Ni-extractant. The extractants have low hydrolytic stability, reverting to their aldehyde precursors when solutions in water-immiscible solvents are contacted with aqueous acid, making them poor candidates for development as reagents for nickel recovery based on pH-swing processes of the type shown above. PMID- 26811998 TI - Acidic pH-induced charge-reversal nanoparticles for accelerated endosomal escape and enhanced microRNA modulation in cancer cells. AB - pH-Induced charge-reversal nanoparticles incorporating microRNA (miRNA) were engineered through a single-step self-assembly of polyelectrolyte complexes. We found that the endosomal/lysosomal acidic environment could trigger the charge reversal of the nanoparticles from negative charge to positive charge and induce the structure alteration of the nanoparticles, which in turn led to accelerated endosomal escape and enhanced miRNA modulation in esophageal cancer cells. PMID- 26811999 TI - Host-only solid-state near-infrared light-emitting electrochemical cells based on interferometric spectral tailoring. AB - Solid-state near-infrared (NIR) light-emitting electrochemical cells (LECs) possess great potential in applications of NIR light sources due to their simple device structure, compatibility with large area and flexible substrates and low operating voltage. However, common host-guest NIR LECs suffer from the problem of significantly enhanced residual host emission upon increasing the bias voltage to achieve a higher NIR light output. A higher NIR light output can only be obtained at the expense of spectral purity in host-guest NIR LECs. To enhance the NIR light output of LECs without sacrificing the spectral purity significantly, a novel approach to generate NIR EL from host-only red-emitting LECs by adjusting the device thickness to modify the microcavity effect is proposed. NIR EL from host-only red-emitting LECs can be realized by adjusting the device thickness to shift the peak wavelength for constructive interference at the NIR spectral region. NIR EL resulting from the microcavity effect is relatively insensitive to bias voltage. Therefore, without losing spectral purity significantly, a 20* enhancement in the NIR output has been obtained in comparison to the previously reported value from host-guest NIR LECs. These results reveal that tailoring the EL spectra of host-only red-emitting LECs via modifying the microcavity effect would be a promising way to generate a higher NIR light output without suffering from the residual host emission problem of host-guest NIR LECs. PMID- 26812001 TI - No effect of multivitamin supplementation on central blood pressure in healthy older people: A randomized controlled trial. AB - BACKGROUND AND AIMS: Central blood pressure rises with age, which increases cardiovascular risk. There is some evidence that nutritional supplements may be useful to reduce central blood pressures in older people, but no studies have investigated the effects of multivitamin supplements for this purpose. This randomized, double-blind, placebo-controlled study investigated the effects of 16 weeks supplementation with gender-specific multivitamin and herbal supplements. METHOD: Participants were healthy individuals, free from heart disease, and included 160 females aged >= 50 and 79 males aged 50-65 years. Analyses of co variance, correcting for baseline cardiovascular assessments, were used to determine the effects of supplementation on central cardiovascular measures including augmentation index, augmentation pressure and pulse pressure. Significance was set at p = 0.016. RESULTS: No effects of multivitamin supplementation were observed in either males or females (respectively) for central augmentation index (p = 0.841; p = 0.296), central augmentation pressure (p = 0.794; p = 0.442), and central pulse pressure (p = 0.078; p = 0.304). Similarly, there was no treatment effect observed for brachial systolic, diastolic or pulse pressures. CONCLUSION: Four months multivitamin supplementation does not appear to exert any benefit to measures of central blood pressure in healthy older people. PMID- 26812002 TI - Lipid lowering drug therapy in patients with coronary heart disease from 24 European countries--Findings from the EUROASPIRE IV survey. AB - OBJECTIVE: Since dyslipidaemia is one of the most important risk factors for coronary heart disease (CHD), lowering of LDL-cholesterol (LDL-C) causes significant reduction in morbidity and mortality, particularly in patients with established CHD. The aim of this survey was to assess how statins were prescribed in CHD patients at discharge after a coronary event from hospitals throughout Europe and how the intake of these drugs was reported by the patients when they were seen more than one year later in relationship with their achieved LDL-C levels. METHODS: 6648 CHD patients' data from centres in 24 European countries were gathered using standardized methods. Lipid measurements were performed in one central laboratory. Patients were divided in three groups: high-intensity statin therapy, moderate or low intensity statin therapy and no statin therapy at all. RESULTS: 90.4% CHD patients were on statin therapy at the time of discharge from the hospital which decreased to 86% one year later. Only 37.6% of these patients were prescribed a high-intensity statin at discharge which even decreased to 32.7% later. In only 6 countries (all of them high-income countries) the number of patients on a high-intensity statin therapy increased substantially after the hospital discharge. It is worrying that statin therapy was discontinued in 11.6% and that only 19.3% of all CHD patients achieved target values of LDL-C < 1.8 mmol/L at the time of interview. CONCLUSIONS: Too many CHD patients with dyslipidaemia are still inadequately treated and most of these patients on statin therapy are not achieving the treatment targets. Therapeutic control of LDL-C is clearly related to the intensity of lipid lowering drug regimen after the CHD event indicating that a considerable potential still exists throughout Europe to reduce CHD mortality and morbidity rates through more efficient LDL-C lowering. PMID- 26812003 TI - Defecation frequency and cardiovascular disease mortality in Japan: The Ohsaki cohort study. AB - BACKGROUND: It has been suggested that constipation is associated with cardiovascular disease (CVD). The association between defecation frequency and CVD mortality in a large population has not been reported hitherto. The aim of this study was to examine whether defecation frequency is related to CVD mortality. METHODS AND RESULTS: A total of 45,112 eligible Japanese men and women aged 40-79 years participated in the Ohsaki Cohort study. Defecation frequency was evaluated at the baseline using a self-administered questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular disease mortality were calculated according to defecation frequency (>= 1 time/day, 1 time/2-3 days, <= 1 time/4 days) by the Cox proportional hazards model. During 13.3 years of follow-up, 2028 participants died due to CVD. Compared with those in the >= 1 time/day group, the risk of overall CVD mortality was significantly higher in the 1 time/2-3 days and <= 1 time/4 days groups; the multivariate HR (95%CI) for 1 time/2-3 days and <= 1 time/4 days was 1.21 (95% CI: 1.08-1.35) and 1.39 (95% CI: 1.06-1.81), respectively. CONCLUSION: A lower defecation frequency was associated with risk of CVD mortality in this Japanese population. Future studies, aiming at elucidating the mechanisms underlying the associations between chronic constipation and risk of CVD mortality, may be facilitated by our findings. PMID- 26812004 TI - The potential of protein-nanomaterial interaction for advanced drug delivery. AB - Nanomaterials, like nanoparticles, micelles, nano-sheets, nanotubes and quantum dots, have great potentials in biomedical fields. However, their delivery is highly limited by the formation of protein corona upon interaction with endogenous proteins. This new identity, instead of nanomaterial itself, would be the real substance the organs and cells firstly encounter. Consequently, the behavior of nanomaterials in vivo is uncontrollable and some undesired effects may occur, like rapid clearance from blood stream; risk of capillary blockage; loss of targeting capacity; and potential toxicity. Therefore, protein nanomaterial interaction is a great challenge for nanomaterial systems and should be inhibited. However, this interaction can also be used to functionalize nanomaterials by forming a selected protein corona. Unlike other decoration using exogenous molecules, nanomaterials functionalized by selected protein corona using endogenous proteins would have greater promise for clinical use. In this review, we aim to provide a comprehensive understanding of protein-nanomaterial interaction. Importantly, a discussion about how to use such interaction is launched and some possible applications of such interaction for advanced drug delivery are presented. PMID- 26812005 TI - Combining the single-walled carbon nanotubes with low voltage electrical stimulation to improve accumulation of nanomedicines in tumor for effective cancer therapy. AB - Effective delivery of biomolecules or functional nanoparticles into target sites has always been the primary objective for cancer therapy. We demonstrated that by combining single-walled carbon nanotubes (SWNTs) with low-voltage (LV) electrical stimulation, biomolecule delivery can be effectively enhanced through reversible electroporation (EP). Clear pore formation in the cell membrane is observed due to LV (50V) pulse electrical stimulation amplified by SWNTs. The cell morphology remains intact and high cell viability is retained. This modality of SWNT + LV pulses can effectively transfer both small molecules and macromolecules into cells through reversible EP. The results of animal studies also suggest that treatment with LV pulses alone cannot increase vascular permeability in tumors unless after the injection of SWNTs. The nanoparticles can cross the permeable vasculature, which enhances their accumulation in the tumor tissue. Therefore, in cancer treatment, both SWNT + LV pulse treatment followed by the injection of LIPO-DOX(r) and SWNT/DOX + LV pulse treatment can increase tumor inhibition and delay tumor growth. This novel treatment modality applied in a human cancer xenograft model can provide a safe and effective therapy using various nanomedicines in cancer treatment. PMID- 26812006 TI - High-performance dendritic contrast agents for X-ray computed tomography imaging using potent tetraiodobenzene derivatives. AB - The use of computed tomography (CT) for vascular imaging is critical in medical emergencies requiring urgent diagnostic decisions, such as cerebral ischemia and many cardiovascular diseases. Small-molecule iodinated contrast media are often injected intravenously as radiopaque agents during CT imaging to achieve high contrast enhancement of vascular systems. The rapid excretion rate of these agents is overcome by injecting a significantly high dose of iodine, which can have serious side effects. Here we report a simple method to prepare blood-pool contrast agents for CT based on dendrimers for the first time using tetraiodobenzene derivatives as potent radiopaque moieties. Excellent in vivo safety has been demonstrated for these small (13-22nm) unimolecular water-soluble dendritic contrast agents, which exhibit high contrast enhancement in the blood pool and effectively extend their blood half-lives. Our method is applicable to virtually any scaffold with suitable surface groups and may fulfill the current need for safer, next-generation iodinated CT contrast agents. PMID- 26812007 TI - Zinc finger-inspired nanohydrogels with glutathione/pH triggered degradation based on coordination substitution for highly efficient delivery of anti-cancer drugs. AB - Biodegradable materials used for drug delivery are of great demand due to their ability to degrade into low molecular weight species and further excrete from the body by metabolism. Herein, we report a new kind of zinc(II) crosslinked poly(methacrylic acid) nanohydrogels (ZCLNs) inspired by zinc finger proteins with dual stimuli-triggered degradation (glutathione and pH) for the first time. Compared with the disulfide bond crosslinked nanohydrogels, this new kind of ZCLNs is beneficial to the degradation of a wide range of cells, including normal cells. Ex vivo fluorescence images showed that the DOX-loaded folate-PEG conjugated zinc(II)-crosslinked polymeric nanohydrogels (FPZCLNs-15) preferentially accumulated in tumor tissue and the accumulation in normal tissues was much less compared with DOX-loaded PZCLNs-15 (non-targeted nanohydrogels) and free DOX, the FPZCLNs-15 (targeting system) delivered DOX to the tumor site with approximately 3.6- and 1.6-fold higher than free DOX and PZCLNs-15, respectively. Meanwhile, the PZCLNs-15 and FPZCLNs-15 reduced the concentration of DOX in the heart by 3.2- and 5.0-fold respectively, as compared to the free DOX. Moreover, a superior tumor growth inhibition and negligible damage to normal organs like the heart and kidney, which is reported to be vulnerable to DOX-associated side effects, are further demonstrated. PMID- 26812008 TI - Seasonal dynamics and microgeographical spatial heterogeneity of malaria along the China-Myanmar border. AB - Malaria transmission is heterogeneous in the Greater Mekong Subregion with most of the cases occurring along international borders. Knowledge of transmission hotspots is essential for targeted malaria control and elimination in this region. This study aimed to determine the dynamics of malaria transmission and possible existence of transmission hotspots on a microgeographical scale along the China-Myanmar border. Microscopically confirmed clinical malaria cases were recorded in five border villages through a recently established surveillance system between January 2011 and December 2014. A total of 424 clinical cases with confirmed spatial and temporal information were analyzed, of which 330 (77.8%) were Plasmodium vivax and 88 (20.8%) were Plasmodium falciparum, respectively. The P. vivax and P. falciparum case ratio increased dramatically from 2.2 in 2011 to 4.7 in 2014, demonstrating that P. vivax malaria has become the predominant parasite species. Clinical infections showed a strong bimodal seasonality. There were significant differences in monthly average incidence rates among the study villages with rates in a village in China being 3-8 folds lower than those in nearby villages in Myanmar. Spatial analysis revealed the presence of clinical malaria hotspots in four villages. This information on malaria seasonal dynamics and transmission hotspots should be harnessed for planning targeted control. PMID- 26812009 TI - The effect of environmental conditions and soil physicochemistry on phosphate stabilisation of Pb in shooting range soils. AB - The stabilisation of Pb in the soil by phosphate is influenced by environmental conditions and physicochemical properties of the soils to which it is applied. Stabilisation of Pb by phosphate was examined in four soils under different environmental conditions. The effect of soil moisture and temperature on stabilisation of Pb by phosphate was examined by measurement of water extractable and bioaccessible Pb, sequential fractionation and X-ray absorption spectroscopy. The addition of humic acid, ammonium nitrate and chloride was also examined for inhibition or improvement of Pb stability with phosphate treatment. The effect of moisture level varied between soils. In soil MB and DA a soil moisture level of 50% water holding capacity was sufficient to maximise stabilisation of Pb, but in soil TV and PE reduction in bioaccessible Pb was inhibited at this moisture level. Providing moisture at twice the soil water holding capacity did not enhance the effect of phosphate on Pb stabilisation. The difference of Pb stability as a result of incubating phosphate treated soils at 18 degrees C and 37 degrees C was relatively small. However wet-dry cycles decreased the effectiveness of phosphate treatment. The reduction in bioaccessible Pb obtained was between 20 and 40% with the most optimal treatment conditions. The reduction in water extractable Pb by phosphate was substantial regardless of incubation conditions and the effect of different temperature and soil moisture regimes was not significant. Selective sequential extraction showed phosphate treatment converted Pb in fraction 1 (exchangeable, acid and water soluble) to fraction 2 (reducible). There were small difference in fraction 4 (residual) Pb and fraction 1 as a result of treatment conditions. X-ray absorption spectroscopy of stabilised PE soil revealed small differences in Pb speciation under varying soil moisture and temperature treatments. The addition of humic acid and chloride produced the greatest effect on Pb speciation in phosphate treated soils. PMID- 26812010 TI - KIF1Bbeta and Neuroblastoma: Failure to Divide and Cull. AB - Neuroblastomas are associated with KIF1Bbeta mutations within tumor suppressor region 1p36. In this issue of Developmental Cell, Li et al. (2016) show that KIF1Bbeta binding releases calcineurin autoinhibition, leading to dephosphorylation of the DRP1 GTPase and subsequent mitochondrial fragmentation. KIF1Bbeta impairment causes mitochondrial hyperfusion, impairing developmental apoptosis and promoting tumorigenesis. PMID- 26812011 TI - A Wacky Bridge to mTORC1 Dimerization. AB - The activity of the mTORC1 protein complex depends on multiple metabolic inputs that regulate dimerization, recruitment to the lysosome, and activation. In this issue of Developmental Cell, David-Morrison et al. (2016) show that the Drosophila protein Wacky and its mammalian counterpart WAC act as adaptors in the process of mTORC1 dimerization. PMID- 26812012 TI - Phagocytes Get Close to Their Enemies. AB - Phagocytosis is key for many organismal functions. In a recent issue of Cell, Freeman et al. (2016) demonstrate a feed-forward signaling mechanism wherein F actin and integrin receptors drive contact formation between phagocytes and antibody-coated solid particles, signaling their engulfment. This mechanism translates nanoscale proximity effects into wider self-propagating signals. PMID- 26812013 TI - Plasticity in the Adult: How Should the Waddington Diagram Be Applied to Regenerating Tissues? AB - Conrad Waddington's eponymous 1957 diagram provided a metaphorical framework for considering how sequential developmental fate decisions allow an egg to develop into an embryo. In recent years, the Waddington diagram has been repurposed to illustrate how cellular identity changes in the context of reprogramming. In this Perspective, we revisit the Waddington diagram in light of the emerging recognition that plasticity is part and parcel of adult regeneration. Specifically, we speculate that the "epigenetic landscapes" that define identity in adult tissues are dynamic, facilitating cellular de-differentiation and trans differentiation in the setting of injury. PMID- 26812014 TI - WAC Regulates mTOR Activity by Acting as an Adaptor for the TTT and Pontin/Reptin Complexes. AB - The ability to sense energy status is crucial in the regulation of metabolism via the mechanistic Target of Rapamycin Complex 1 (mTORC1). The assembly of the TTT Pontin/Reptin complex is responsive to changes in energy status. Under energy sufficient conditions, the TTT-Pontin/Reptin complex promotes mTORC1 dimerization and mTORC1-Rag interaction, which are critical for mTORC1 activation. We show that WAC is a regulator of energy-mediated mTORC1 activity. In a Drosophila screen designed to isolate mutations that cause neuronal dysfunction, we identified wacky, the homolog of WAC. Loss of Wacky leads to neurodegeneration, defective mTOR activity, and increased autophagy. Wacky and WAC have conserved physical interactions with mTOR and its regulators, including Pontin and Reptin, which bind to the TTT complex to regulate energy-dependent activation of mTORC1. WAC promotes the interaction between TTT and Pontin/Reptin in an energy-dependent manner, thereby promoting mTORC1 activity by facilitating mTORC1 dimerization and mTORC1-Rag interaction. PMID- 26812016 TI - The 1p36 Tumor Suppressor KIF 1Bbeta Is Required for Calcineurin Activation, Controlling Mitochondrial Fission and Apoptosis. AB - KIF1Bbeta is a candidate 1p36 tumor suppressor that regulates apoptosis in the developing sympathetic nervous system. We found that KIF1Bbeta activates the Ca(2+)-dependent phosphatase calcineurin (CN) by stabilizing the CN-calmodulin complex, relieving enzymatic autoinhibition and enabling CN substrate recognition. CN is the key mediator of cellular responses to Ca(2+) signals and its deregulation is implicated in cancer, cardiac, neurodegenerative, and immune disease. We show that KIF1Bbeta affects mitochondrial dynamics through CN dependent dephosphorylation of Dynamin-related protein 1 (DRP1), causing mitochondrial fission and apoptosis. Furthermore, KIF1Bbeta actuates recognition of all known CN substrates, implying a general mechanism for KIF1Bbeta in Ca(2+) signaling and how Ca(2+)-dependent signaling is executed by CN. Pathogenic KIF1Bbeta mutations previously identified in neuroblastomas and pheochromocytomas all fail to activate CN or stimulate DRP1 dephosphorylation. Importantly, KIF1Bbeta and DRP1 are silenced in 1p36 hemizygous-deleted neuroblastomas, indicating that deregulation of calcineurin and mitochondrial dynamics contributes to high-risk and poor-prognosis neuroblastoma. PMID- 26812015 TI - Maternal DNA Methylation Regulates Early Trophoblast Development. AB - Critical roles for DNA methylation in embryonic development are well established, but less is known about its roles during trophoblast development, the extraembryonic lineage that gives rise to the placenta. We dissected the role of DNA methylation in trophoblast development by performing mRNA and DNA methylation profiling of Dnmt3a/3b mutants. We find that oocyte-derived methylation plays a major role in regulating trophoblast development but that imprinting of the key placental regulator Ascl2 is only partially responsible for these effects. We have identified several methylation-regulated genes associated with trophoblast differentiation that are involved in cell adhesion and migration, potentially affecting trophoblast invasion. Specifically, trophoblast-specific DNA methylation is linked to the silencing of Scml2, a Polycomb Repressive Complex 1 protein that drives loss of cell adhesion in methylation-deficient trophoblast. Our results reveal that maternal DNA methylation controls multiple differentiation-related and physiological processes in trophoblast via both imprinting-dependent and -independent mechanisms. PMID- 26812017 TI - Mechanistic Basis of Organization of the Harmonin/USH1C-Mediated Brush Border Microvilli Tip-Link Complex. AB - Brush border microvilli are actin-based protrusions lining the apical surface of epithelial cells in intestines and proximal tubules of kidneys. While brush border microvilli resemble the relatively well-characterized stereocilia of hair cells, the mechanistic basis of tip-link complex organization in microvilli is poorly understood. Here, we have biochemically and structurally characterized the following pairs of interactions: protocadherin 24 and Harmonin (also known as USH1C or AIE-75), Harmonin and myosin VIIb (MYO7B), Harmonin and ANKS4B, and ANKS4B and MYO7B. We show that Harmonin, ANKS4B, and MYO7B form a stable ternary complex for anchoring microvilli tip-link cadherins. Despite having only Harmonin in common, the microvilli and the stereocilia tip-link complexes are formed via strikingly similar interaction modes. These results not only provide insight into the mechanistic bases of brush border microvilli formation and maintenance but may also be valuable for understanding some gut and/or kidney diseases caused by perturbations of brush border microvilli structures. PMID- 26812018 TI - ANKS4B Is Essential for Intermicrovillar Adhesion Complex Formation. AB - Transporting and sensory epithelial cells shape apical specializations using protocadherin-based adhesion. In the enterocyte brush border, protocadherin function requires a complex of cytoplasmic binding partners, although the composition of this complex and logic governing its assembly remain poorly understood. We found that ankyrin repeat and sterile alpha motif domain containing 4B (ANKS4B) localizes to the tips of adherent brush border microvilli and is essential for intermicrovillar adhesion. ANKS4B interacts with USH1C and MYO7B, which link protocadherins to the actin cytoskeleton. ANKS4B and USH1C also bind to the MYO7B cargo-binding tail at distinct sites. However, a tripartite complex only forms if ANKS4B and MYO7B are first activated by USH1C. This study uncovers an essential role for ANKS4B in brush border assembly, reveals a hierarchy in the molecular interactions that drive intermicrovillar adhesion, and informs our understanding of diseases caused by mutations in USH1C and ankyrin repeat proteins, such as Usher syndrome. PMID- 26812019 TI - Profilin Interaction with Actin Filament Barbed End Controls Dynamic Instability, Capping, Branching, and Motility. AB - Cell motility and actin homeostasis depend on the control of polarized growth of actin filaments. Profilin, an abundant regulator of actin dynamics, supports filament assembly at barbed ends by binding G-actin. Here, we demonstrate how, by binding and destabilizing filament barbed ends at physiological concentrations, profilin also controls motility, cell migration, and actin homeostasis. Profilin enhances filament length fluctuations. Profilin competes with Capping Protein at barbed ends, which generates a lower amount of profilin-actin than expected if barbed ends were tightly capped. Profilin competes with barbed end polymerases, such as formins and VopF, and inhibits filament branching by WASP-Arp2/3 complex by competition for filament barbed ends, accounting for its as-yet-unknown effects on motility and metastatic cell migration observed in this concentration range. In conclusion, profilin is a major coordinator of polarized growth of actin filaments, controlled by competition between barbed end cappers, trackers, destabilizers, and filament branching machineries. PMID- 26812020 TI - Real-Time Three-Dimensional Cell Segmentation in Large-Scale Microscopy Data of Developing Embryos. AB - We present the Real-time Accurate Cell-shape Extractor (RACE), a high-throughput image analysis framework for automated three-dimensional cell segmentation in large-scale images. RACE is 55-330 times faster and 2-5 times more accurate than state-of-the-art methods. We demonstrate the generality of RACE by extracting cell-shape information from entire Drosophila, zebrafish, and mouse embryos imaged with confocal and light-sheet microscopes. Using RACE, we automatically reconstructed cellular-resolution tissue anisotropy maps across developing Drosophila embryos and quantified differences in cell-shape dynamics in wild-type and mutant embryos. We furthermore integrated RACE with our framework for automated cell lineaging and performed joint segmentation and cell tracking in entire Drosophila embryos. RACE processed these terabyte-sized datasets on a single computer within 1.4 days. RACE is easy to use, as it requires adjustment of only three parameters, takes full advantage of state-of-the-art multi-core processors and graphics cards, and is available as open-source software for Windows, Linux, and Mac OS. PMID- 26812022 TI - Impact of magnetic fluctuations on lattice excitations in fcc nickel. AB - The spin-space averaging formalism is applied to compute atomic forces and phonon spectra for magnetically excited states of fcc nickel. Transverse and longitudinal magnetic fluctuations are taken into account by a combination of magnetic special quasi random structures and constrained spin-density-functional theory. It turns out that for fcc Ni interatomic force constants and phonon spectra are almost unaffected by both kinds of spin fluctuations. Given the computational expense to simulate coupled magnetic and atomic fluctuations, this insight facilitates computational modeling of magnetic alloys such as Ni-based superalloys. PMID- 26812021 TI - Genetic testing for hereditary cancer predisposition: BRCA1/2, Lynch syndrome, and beyond. AB - Obstetrician/gynecologists and gynecologic oncologists serve an integral role in the care of women at increased hereditary risk of cancer. Their contribution includes initial identification of high risk patients, screening procedures like bimanual exam, trans-vaginal ultrasound and endometrial biopsy, prophylaxis via TAH and/or BSO, and chemoprevention. Further, gynecologists also serve a central role in the management of the secondary repercussions of efforts to mitigate increased cancer risks, including vasomotor symptoms, sexual function, bone health, cardiovascular disease, and mental health. The past several years has seen multiple new high and moderate penetrance genes introduced into the clinical care of women at increased risk of gynecologic malignancy. Awareness of these new genes and the availability of new multi-gene panel tests is critical for providers on the front-line of women's health. PMID- 26812023 TI - Investigation of the Inertness to Hydrolysis of Platinum(IV) Prodrugs. AB - Platinum(IV) complexes are an important class of compounds that can act as prodrugs, and due to their inertness, if correctly designed, they could have low toxicity outside the cancer cell and improve the pharmacological properties of the platinum(II) anticancer agents that are currently used in the clinic. Because of the efforts that are concentrated on the use of axial ligands able to control the reduction potentials, lipophilicity, charge, selectivity, targeting, and cell uptake of the Pt(IV) complexes, we considered to be of interest to probe the inertness of such complexes that is assumed to be a fulfilled prerequisite. To this aim, a density functional theory computational analysis of the hydrolysis mechanism and the corresponding energy profiles for a series of Pt(IV) derivatives of cisplatin, carboplatin, and oxaliplatin with acetato, haloacetato, and chlorido ligands was performed to probe their stability in biological fluids. The heights of the barriers calculated along the hydrolysis pathways for the associative displacement of ligands both in axial and equatorial positions confirm that Pt(IV) complexes are, in general, more inert than the corresponding Pt(II) drugs even if inertness is lower than expected. Some exceptions exist, such as derivatives of oxaliplatin for the hydrolysis in equatorial position. The nature of the axial ligands influences the course of the hydrolysis reaction even if a decisive role is played by the ligands in equatorial positions. The mechanism of the aquation in axial position of cisplatin Pt(IV) derivative with two chlorido axial ligands assisted by Pt(II) cisplatin was elucidated, and the calculated activation energy confirms the catalytic role played by the Pt(II) complex. PMID- 26812024 TI - Characterising granuloma regression and liver recovery in a murine model of schistosomiasis japonica. AB - For hepatic schistosomiasis the egg-induced granulomatous response and the development of extensive fibrosis are the main pathologies. We used a Schistosoma japonicum-infected mouse model to characterise the multi-cellular pathways associated with the recovery from hepatic fibrosis following clearance of the infection with the anti-schistosomal drug, praziquantel. In the recovering liver splenomegaly, granuloma density and liver fibrosis were all reduced. Inflammatory cell infiltration into the liver was evident, and the numbers of neutrophils, eosinophils and macrophages were significantly decreased. Transcriptomic analysis revealed the up-regulation of fatty acid metabolism genes and the identification of Peroxisome proliferator activated receptor alpha as the upstream regulator of liver recovery. The aryl hydrocarbon receptor signalling pathway which regulates xenobiotic metabolism was also differentially up-regulated. These findings provide a better understanding of the mechanisms associated with the regression of hepatic schistosomiasis. PMID- 26812025 TI - Hemozoin is a product of heme detoxification in the gut of the most medically important species of the family Opisthorchiidae. AB - Many species of trematodes such as Schistosoma spp., Fasciola hepatica and Echinostoma trivolvis are blood-feeding parasites. Nevertheless, there is no consensus on the feeding habits of the family Opisthorchiidae (Opisthorchis felineus, Opisthorchis viverrini and Clonorchis sinensis). Previously, histological studies of O. felineus and C. sinensis revealed some dark stained material in their gut lumen. In this study we conducted a comprehensive analysis of the gut contents of three members of the family Opisthorchiidae (O. felineus, O. viverrini and C. sinensis). Using transmission electron microscopy, we demonstrated for the first known time the presence of disintegrating blood cells in the gut of O. felineus as well as electron-dense crystals in the gut of O. felineus and C. sinensis. Electron energy loss spectroscopy revealed iron atoms in these crystals, and mass spectrometry of the purified pigment demonstrated the presence of heme. Fourier-transform infrared spectroscopy identified the signature peaks of the common iron-carboxylate bond characteristic in crystals isolated from O. felineus and C. sinensis. Scanning electron microscopy showed layered ovoid crystals of various sizes from 50 nm to 2 MUm. Morphological, chemical and paramagnetic properties of these crystals were similar to those of hemozoin from Schistosoma mansoni. Crystal formation occurs on the surface of lipid droplets in O. felineus and C. sinensis guts. Our results suggest that the diet of O. felineus and C. sinensis includes blood. Detoxification of the free heme produced during the digestion proceeds via formation of insoluble crystals that contain iron and heme dimers, i.e. crystals of hemozoin. Furthermore, we believe that biocrystallisation of hemozoin takes place on the surface of the lipid droplets, similar to S. mansoni. Hemozoin was not detected in the closely related species O. viverrini. PMID- 26812027 TI - Individual and combined in vitro (anti)androgenic effects of certain food additives and cosmetic preservatives. AB - The individual and combined (binary mixtures) (anti)androgenic effect of butylparaben (BuPB), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and propyl gallate (PG) was evaluated using the MDA-kb2 cell line. Exposing these cells to AR agonists results in the expression of the reporter gene (encoding for luciferase) and luminescence can be measured in order to monitor the activity of the reporter protein. In case of the evaluation of the anti androgenic effect, the individual test compounds or binary mixtures were tested in the presence of a fixed concentration of a strong AR agonist (1000 pM 5-alpha dihydrotestosterone; DHT). Cell viability was assessed using a resazurin based assay. For PG, this is the first report in the literature concerning its (anti)androgenic activity. In case of both individual and mixture testing none of the compounds or binary combinations showed androgenic activity. When tested in the presence of DHT, BuPB, BHA and BHT proved to be weak anti-androgens and this was confirmed during the evaluation of binary mixtures (BuPB+BHA, BuPB+BHT and BHA+BHT). Besides performing the in vitro testing of the binary combinations, two mathematical models (dose addition and response addition) were evaluated in terms of accuracy of prediction of the anti-androgenic effect of the selected binary mixtures. The dose addition model guaranteed a good correlation between the experimental and predicted data. However, no estimation was possible in case of mixtures containing PG, due to the lack of effect of the compound in case of the individual testing. PMID- 26812028 TI - Importation of Fosfomycin Resistance fosA3 Gene to Europe. PMID- 26812026 TI - Amblyomma sculptum tick saliva: alpha-Gal identification, antibody response and possible association with red meat allergy in Brazil. AB - The anaphylaxis response is frequently associated with food allergies, representing a significant public health hazard. Recently, exposure to tick bites and production of specific IgE against alpha-galactosyl (alpha-Gal)-containing epitopes has been correlated to red meat allergy. However, this association and the source of terminal, non-reducing alpha-Gal-containing epitopes have not previously been established in Brazil. Here, we employed the alpha-1,3 galactosyltransferase knockout mouse (alpha1,3-GalT-KO) model and bacteriophage Qbeta-virus like particles (Qbeta-VLPs) displaying Galalpha1,3Galbeta1,4GlcNAc (Galalpha3LN) epitopes to investigate the presence of alpha-Gal-containing epitopes in the saliva of Amblyomma sculptum, a species of the Amblyomma cajennense complex, which represents the main tick that infests humans in Brazil. We confirmed that the alpha-1,3-galactosyltransferase knockout animals produce significant levels of anti-alpha-Gal antibodies against the Galalpha1,3Galbeta1,4GlcNAc epitopes displayed on Qbeta-virus like particles. The injection of A. sculptum saliva or exposure to feeding ticks was also found to induce both IgG and IgE anti-alpha-Gal antibodies in alpha-1,3 galactosyltransferase knockout mice, thus indicating the presence of alpha-Gal containing epitopes in the tick saliva. The presence of alpha-Gal-containing epitopes was confirmed by ELISA and immunoblotting following removal of terminal alpha-Gal epitopes by alpha-galactosidase treatment. These results suggest for the first known time that bites from the A. sculptum tick may be associated with the unknown etiology of allergic reactions to red meat in Brazil. PMID- 26812030 TI - A Rare Cause of Persistent Rectal Bleeding. PMID- 26812032 TI - The expression pattern and inhibitory influence of Tenascin-C on the growth of spiral ganglion neurons suggest a regulatory role as boundary formation molecule in the postnatal mouse inner ear. AB - Sensorineural hearing loss, as a consequence of acoustic trauma, aging, genetic defects or ototoxic drugs, is highly associated with irreversible damage of cochlear hair cells (HCs) and secondary degeneration of spiral ganglion (SG) cells. Cochlear implants (CIs), which bypass the lost HC function by direct electrical stimulation of the remaining auditory neurons, offer an effective therapy option. Several studies imply that components of the extracellular matrix (ECM) have a great impact on the adhesion and growth of spiral ganglion neurons (SGNs) during development. Based on these findings, ECM proteins might act as bioactive CI substrates to optimize the electrode-nerve interface and to improve efficacy of these implants. In the present study, we focused on the ECM glycoproteins Tenascin-C (TN-C), Laminin (LN), and Fibronectin (FN), which show a prominent expression along the growth route of SGNs and the niche around HCs during murine postnatal development in vivo. We compared their influence on adhesion, neurite length, and neurite number of SGNs in vitro. Moreover, we studied the expression of the chondroitin sulfate proteoglycan (CSPG) dermatan sulfate-dependent proteoglycan-1 (DSD-1-PG), an interaction partner of TN-C. In sum, our in vitro data suggest that TN-C acts as an anti-adhesive and inhibitory factor for the growth of SGNs. The DSD-1 carbohydrate epitope is specifically localized to HC stereocilia and SG fibers. Interestingly, TN-C and the DSD-1-PG exhibit a mutually exclusive expression pattern, with the exception of a very restricted region beneath the habenula perforata, where SG neurites grow through the basilar membrane (BM) toward the HCs. The complementary expression of TN-C, LN, FN, and the DSD-1 epitope suggests that TN-C may act as an important boundary formation molecule in the developing postnatal mouse inner ear, which makes it a promising candidate to regulate neurite outgrowth in the light of CIs. PMID- 26812031 TI - Suppressors of cytokine signalling in ankylosing spondylitis and their associations with disease severity, acute-phase reactants and serum cytokines. AB - OBJECTIVES: To investigate the suppressors of cytokine signalling (SOCS1 and SOCS3) expression in peripheral blood cells in ankylosing spondylitis (AS), and their associations with clinical and laboratory manifestations. METHODS: The levels of SOCS1 and SOCS3 mRNA in peripheral blood mononuclear cells (PBMCs), T cells and monocytes were measured by RT-PCR in 53 AS patients and 31 healthy controls. Patient's serum IL-6, IL-10 and IL-17A levels were determined by ELISA. We evaluated patient's disease activity, functional ability and global assessment, and tested their ESR, CRP and IgA levels. RESULTS: Cellular SOCS1 expression did not show significant differences between AS patients and controls. However, T cells SOCS1 decreased significantly in the AS subgroup with lower ESR than controls (p=0.013). PBMCs (p=0.047) and T cells (p=0.035) SOCS1 decreased significantly in the AS subgroup with lower CRP than controls. Importantly, SOCS3 expression increased significantly in AS patients compared to the controls in PBMCs (p=0.025), T cells (p=0.003) and monocytes (p=0.009). Moreover, PBMCs SOCS3 correlated with ESR (r=0.297, p=0.031) and CRP (r=0.320, p=0.019). T cells SOCS3 correlated with BASFI (r=0.337, p=0.015), ESR (r=0.435, p=0.001) and CRP (r=0.300, p=0.029). Monocytes SOCS3 correlated with ESR (r=0.281, p=0.041) and IgA (r=0.426, p=0.006). Furthermore, T cells SOCS1 (r=-0.454, p=0.023) and T cells SOCS3 (r=-0.405, p=0.045) negatively correlated with serum IL-17A. Monocytes SOCS3 negatively correlated with serum IL-6 (r=-0.584, p=0.002). CONCLUSIONS: The decreased SOCS1 and increased SOCS3 expression in AS PBMCs and T cells, and their correlation with patient's functional ability, acute-phase reactants and serum pro-inflammatory cytokines suggested that SOCS may participate in the pathogenesis of AS. PMID- 26812033 TI - Neuronal death in the dorsal root ganglion after sciatic nerve injury does not depend on sortilin. AB - Injury to the sciatic nerve induces loss of sensory neurons in the affected dorsal root ganglia (DRGs). Previous studies have suggested the involvement of the neurotrophin receptors p75 neurotrophin receptor (p75(NTR)) and sortilin, proposing that sensory neuron subpopulations undergo proneurotrophin-induced apoptosis in a similar manner to what can be observed in the CNS following injury. To further investigate this hypothesis we induced sciatic nerve injury in sortilin-deficient mice, thereby preventing apoptotic signaling of proneurotrophins via the sortilin-p75(NTR) receptor complex. Using an unbiased stereological approach we found that loss of sortilin did not prevent the injury induced loss of DRG neurons. This result demonstrates that previous findings linking p75(NTR) and proneurotrophins to loss of sensory neurons need to involve sortilin-independent pathways and suggests that proneurotrophins may elicit different functions in the CNS and PNS. PMID- 26812034 TI - Pain sensitivity following loss of cholinergic basal forebrain (CBF) neurons in the rat. AB - Flexion/withdrawal reflexes are attenuated by spinal, intracerebroventricular (ICV) and systemic delivery of cholinergic agonists. In contrast, some affective reactions to pain are suppressed by systemic cholinergic antagonism. Attention to aversive stimulation can be impaired, as is classical conditioning of fear and anxiety to aversive stimuli and psychological activation of stress reactions that exacerbate pain. Thus, in contrast to the suppressive effects of cholinergic agonism on reflexes, pain sensitivity and affective reactions to pain could be attenuated by reduced cerebral cholinergic activation. This possibility was evaluated in the present study, using an operant test of escape from nociceptive thermal stimulation (10 degrees C and 44.5 degrees C) before and after destruction of basal forebrain cholinergic neurons. ICV injection of 192 IgG saporin produced widespread loss of basal forebrain cholinergic innervation of the cerebral cortex and hippocampus. Post-injection, escape from thermal stimulation was decreased with no indication of recovery for upto 19 weeks. Also, the normal hyperalgesic effect of sound stress was absent after ICV 192-sap. Effects of cerebral cholinergic denervation or stress on nociceptive licking and guarding reflexes were not consistent with the effects on operant escape, highlighting the importance of evaluating pain sensitivity of laboratory animals with an operant behavioral test. These results reveal that basal forebrain cholinergic transmission participates in the cerebral processing of pain, which may be relevant to the pain sensitivity of patients with Alzheimer's disease who have prominent degeneration of basal forebrain cholinergic neurons. PMID- 26812035 TI - Neonatal ventral hippocampus lesion changes nuclear restricted protein/brain (NRP/B) expression in hippocampus, cortex and striatum in developmental periods of rats. AB - Schizophrenia is conceptualized as a neurodevelopmental disorder in which developmental alterations in immature brain systems are not clear. Rats with neonatal ventral hippocampal lesions (NVHL) can exhibit schizophrenia-like behaviors, and these rats have been widely used to study the developmental mechanisms of schizophrenia. The nuclear restricted protein/brain (NRP/B) is a nuclear matrix protein that is critical for the normal development of the neuronal system. This study assessed the effect of NVHL induced by the administration of ibotenic acid on the protein expression of NRP/B in the hippocampus, cortex and striatum in pre- and post-pubertal rats. The expressions of NeuN in various developmental periods were assessed accordingly. Sprague Dawley rat pups were administered ibotenic acid at postnatal day (PD) 7. Western blotting and an immunofluorescence staining analysis showed that the expression of NRP/B was significantly decreased in the hippocampus, cortex and striatum of the NVHL rats at PD14, 28 and 42. The expressions of NeuN were decreased accordingly. In vitro experiment showed the NRP/B knockdown can decrease the Tuj1 expression in cultured cortical neurons. The data suggest that NVHL induces a change in NRP/B expression that affects neurons in the developmental period. PMID- 26812036 TI - Microarray expression profile analysis of long noncoding RNAs in premature brain injury: A novel point of view. AB - Long noncoding RNAs (lncRNAs) are abundant in the central nervous system and have a key role in brain function as well as many neurological disorders. However, the regulatory function of lncRNAs in the premature brain has not been well studied. This study described the expression profile of lncRNAs in premature mice using microarray technology. 1999 differentially expressed lncRNAs and 955 differentially expressed mRNAs were identified. Gene Ontology (GO) and pathway analysis showed that these lncRNAs were involved in multiple biological processes, including the nervous system development and inflammatory response. Additionally, the lncRNA-mRNA-network and TF-gene-lncRNA-network were constructed to identify core regulatory lncRNAs and transcription factors. The sex determining region of Y chromosome (SRY) gene may be a key transcription factor that regulates premature brain development and injury. This study for the first time represents an expression profile of differentially expressed lncRNAs in the premature brain and may provide a novel point of view into the mechanisms of premature brain injury. PMID- 26812037 TI - Nitric oxide in the prelimbic medial prefrontal cortex is involved in the anxiogenic-like effect induced by acute restraint stress in rats. AB - Neurons containing the neuronal nitric oxide synthase (nNOS) enzyme are located in brain areas related to defensive behavior, such as the ventromedial prefrontal cortex (vMPFC). Rats exposed to a live predator (a cat) present anxiety-like behavior and an increased number of nNOS-positive neurons in this brain area one week later. Moreover, stress-related behavioral changes in rodents can be prevented by systemic or local vMPFC nNOS inhibition. In the present study we investigated if acute restraint stress (RS)-induced delayed (one-week) anxiogenic like effect was associated with increased nNOS expression or activity in the vMPFC. Furthermore, we also tested if local pharmacological nNOS inhibition would prevent stress-induced behavioral changes. Male Wistar rats were submitted to RS for 3h and tested in the elevated plus maze (EPM) 24h or 7 days later. Two hours after the EPM test, their brains were removed, processed and nNOS expression in the vMPFC was evaluated by immunohistochemistry. Another group of animals was used for measuring NO metabolites (NOx; an indirect measure of NOS activity) immediately after the EPM test, 24h after RS. Independent groups had guide cannula implanted bilaterally into the prelimbic (PL) portion of vMPFC. Five to six days after surgery, the animals were submitted to RS and 24h later received local administration of the nNOS inhibitor, N-propyl-l-arginine (NPLA; 0.04 nmol). They were tested in the EPM 10 min later. RS-induced anxiogenic-like effect was accompanied by increased nNOS expression in the PL (p<0.05), but not in the infralimbic (IL) vMPFC, both 24h and 7 days after RS. Moreover, open-arm exploration of the EPM was negatively correlated with nNOS expression (p<0.05) and NOx levels (p<0.05) in the PL. The anxiogenic-like effect observed 24h after RS was prevented by NPLA (p<0.05). Our results suggest that RS-induced anxiogenic like effect might depend on increased nNOS-mediated signaling in the PL MPFC. PMID- 26812038 TI - Expression level of P2X7 receptor is a determinant of ATP-induced death of mouse cultured neurons. AB - Activation of P2X7 receptor (P2X7R), a purinergic receptor, expressed by neurons is well-known to induce their death, but whether or not their sensitivity to ATP depends on its expression levels remains unclear. Here, we examined the effect of the expression level of P2X7Rs on cell viability using pure neuron cultures, co cultures with astrocytes derived from SJL- and ddY-strain mice, and mouse P2X7R expressing HEK293T cell systems. Treatment of pure neuron cultures with 5mM ATP for 2h, followed by 3-h incubation in fresh medium, resulted in death of both types of neurons, and their death was prevented by administration of P2X7R specific antagonists. In both SJL- and ddY-neurons, ATP-induced neuronal death was inhibited by a mitochondrial permeability transition pore inhibitor cyclosporine A, mitochondrial dysfunction being involved in their death. The ATP induced neuronal death was greater for SJL-neurons than for ddY-ones, this being correlated with the expression level of P2X7R in them, and the same results were obtained for the HEK293T cell systems. Co-culture of neurons with astrocytes increased the ATP-induced neuronal death compared to the case of pure neuron cultures. Overall, we reveal that neuronal vulnerability to ATP depends on the expression level of P2X7R, and co-existence of astrocytes exacerbates ATP-induced neuronal death. PMID- 26812039 TI - Elucidating the Magnetic Anisotropy and Relaxation Dynamics of Low-Coordinate Lanthanide Compounds. AB - The magnetic relaxation and anisotropy of 3- and 4-coordinate lanthanide complexes were systematically investigated, and the change of SMM behavior originating from the equatorially coordinating ligand field was successfully elucidated through combined experimental and theoretical studies. Remarkably, a novel approach taking into account the different contributions of atomic charges, dipole moments, and quadrupole moments was used to map the electrostatic potential around the metal center in the Dy(III) derivatives, revealing the key role played by the ligands as a whole and not just by the coordinating donor atoms as often considered. PMID- 26812040 TI - Blood metabolite markers of neocortical amyloid-beta burden: discovery and enrichment using candidate proteins. AB - We believe this is the first study to investigate associations between blood metabolites and neocortical amyloid burden (NAB) in the search for a blood-based biomarker for Alzheimer's disease (AD). Further, we present the first multi-modal analysis of blood markers in this field. We used blood plasma samples from 91 subjects enrolled in the University of California, San Francisco Alzheimer's Disease Research Centre. Non-targeted metabolomic analysis was used to look for associations with NAB using both single and multiple metabolic feature models. Five metabolic features identified subjects with high NAB, with 72% accuracy. We were able to putatively identify four metabolites from this panel and improve the model further by adding fibrinogen gamma chain protein measures (accuracy=79%). One of the five metabolic features was studied in the Alzheimer's Disease Neuroimaging Initiative cohort, but results were inconclusive. If replicated in larger, independent studies, these metabolic features and proteins could form the basis of a blood test with potential for enrichment of amyloid pathology in anti amyloid trials. PMID- 26812042 TI - Dysfunctional information processing during an auditory event-related potential task in individuals with Internet gaming disorder. AB - Internet gaming disorder (IGD) leading to serious impairments in cognitive, psychological and social functions has gradually been increasing. However, very few studies conducted to date have addressed issues related to the event-related potential (ERP) patterns in IGD. Identifying the neurobiological characteristics of IGD is important to elucidate the pathophysiology of this condition. P300 is a useful ERP component for investigating electrophysiological features of the brain. The aims of the present study were to investigate differences between patients with IGD and healthy controls (HCs), with regard to the P300 component of the ERP during an auditory oddball task, and to examine the relationship of this component to the severity of IGD symptoms in identifying the relevant neurophysiological features of IGD. Twenty-six patients diagnosed with IGD and 23 age-, sex-, education- and intelligence quotient-matched HCs participated in this study. During an auditory oddball task, participants had to respond to the rare, deviant tones presented in a sequence of frequent, standard tones. The IGD group exhibited a significant reduction in response to deviant tones compared with the HC group in the P300 amplitudes at the midline centro-parietal electrode regions. We also found a negative correlation between the severity of IGD and P300 amplitudes. The reduced amplitude of the P300 component in an auditory oddball task may reflect dysfunction in auditory information processing and cognitive capabilities in IGD. These findings suggest that reduced P300 amplitudes may be candidate neurobiological marker for IGD. PMID- 26812041 TI - Applications of time-series analysis to mood fluctuations in bipolar disorder to promote treatment innovation: a case series. AB - Treatment innovation for bipolar disorder has been hampered by a lack of techniques to capture a hallmark symptom: ongoing mood instability. Mood swings persist during remission from acute mood episodes and impair daily functioning. The last significant treatment advance remains Lithium (in the 1970s), which aids only the minority of patients. There is no accepted way to establish proof of concept for a new mood-stabilizing treatment. We suggest that combining insights from mood measurement with applied mathematics may provide a step change: repeated daily mood measurement (depression) over a short time frame (1 month) can create individual bipolar mood instability profiles. A time-series approach allows comparison of mood instability pre- and post-treatment. We test a new imagery-focused cognitive therapy treatment approach (MAPP; Mood Action Psychology Programme) targeting a driver of mood instability, and apply these measurement methods in a non-concurrent multiple baseline design case series of 14 patients with bipolar disorder. Weekly mood monitoring and treatment target data improved for the whole sample combined. Time-series analyses of daily mood data, sampled remotely (mobile phone/Internet) for 28 days pre- and post treatment, demonstrated improvements in individuals' mood stability for 11 of 14 patients. Thus the findings offer preliminary support for a new imagery-focused treatment approach. They also indicate a step in treatment innovation without the requirement for trials in illness episodes or relapse prevention. Importantly, daily measurement offers a description of mood instability at the individual patient level in a clinically meaningful time frame. This costly, chronic and disabling mental illness demands innovation in both treatment approaches (whether pharmacological or psychological) and measurement tool: this work indicates that daily measurements can be used to detect improvement in individual mood stability for treatment innovation (MAPP). PMID- 26812043 TI - Rapid effects of deep brain stimulation reactivation on symptoms and neuroendocrine parameters in obsessive-compulsive disorder. AB - Improvement of obsessions and compulsions by deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) is often preceded by a rapid and transient mood elevation (hypomania). In a previous study we showed that improvement of mood by DBS for OCD is associated with a decreased activity of the hypothalamus pituitary adrenal axis. The aim of our present study was to evaluate the time course of rapid clinical changes following DBS reactivation in more detail and to assess their association with additional neuroendocrine parameters. We included therapy-refractory OCD patients treated with DBS (>1 year) and performed a baseline assessment of symptoms, as well as plasma concentrations of thyroid stimulating hormone (TSH), prolactin, growth hormone, copeptin and homovanillic acid. This was repeated after a 1-week DBS OFF condition. Next, we assessed the rapid effects of DBS reactivation by measuring psychiatric symptom changes using visual analog scales as well as repeated neuroendocrine measures after 30 min, 2 h and 6 h. OCD, anxiety and depressive symptoms markedly increased during the 1 week OFF condition and decreased again to a similar extent already 2 h after DBS reactivation. We found lower plasma prolactin (41% decrease, P=0.003) and TSH (39% decrease, P=0.003) levels during DBS OFF, which increased significantly already 30 min after DBS reactivation. The rapid and simultaneous increase in TSH and prolactin is likely to result from stimulation of hypothalamic thyrotropin releasing hormone (TRH), which may underlie the commonly observed transient mood elevation following DBS. PMID- 26812044 TI - Toward dissecting the etiology of schizophrenia: HDAC1 and DAXX regulate GAD67 expression in an in vitro hippocampal GABA neuron model. AB - Schizophrenia (SZ) is associated with GABA neuron dysfunction in the hippocampus, particularly the stratum oriens of sector CA3/2. A gene expression profile analysis of human postmortem hippocampal tissue followed by a network association analysis had shown a number of genes differentially regulated in SZ, including the epigenetic factors HDAC1 and DAXX. To characterize the contribution of these factors to the developmental perturbation hypothesized to underlie SZ, lentiviral vectors carrying short hairpin RNA interference (shRNAi) for HDAC1 and DAXX were used. In the hippocampal GABA neuron culture model, HiB5, transduction with HDAC1 shRNAi showed a 40% inhibition of HDAC1 mRNA and a 60% inhibition of HDAC1 protein. GAD67, a enzyme associated with GABA synthesis, was increased twofold (mRNA); the protein showed a 35% increase. The expression of DAXX, a co-repressor of HDAC1, was not influenced by HDAC1 inhibition. Transduction of HiB5 cells with DAXX shRNAi resulted in a 30% inhibition of DAXX mRNA that translated into a 90% inhibition of DAXX protein. GAD1 mRNA was upregulated fourfold, while its protein increased by ~30%. HDAC1 expression was not altered by inhibition of DAXX. However, a physical interaction between HDAC1 and DAXX was demonstrated by co immunoprecipitation. Inhibition of HDAC1 or DAXX increased expression of egr-1, transcription factor that had previously been shown to regulate the GAD67 promoter. Our in vitro results point to a key role of both HDAC1 and DAXX in the regulation of GAD67 in GABAergic HiB5 cells, strongly suggesting that these epigenetic/transcription factors contribute to mechanisms underlying GABA cell dysfunction in SZ. PMID- 26812045 TI - Multiplicity of Sulfate and Molybdate Transporters and Their Role in Nitrogen Fixation in Rhizobium leguminosarum bv. viciae Rlv3841. AB - Rhizobium leguminosarum Rlv3841 contains at least three sulfate transporters, i.e., SulABCD, SulP1 and SulP2, and a single molybdate transporter, ModABC. SulABCD is a high-affinity transporter whose mutation prevented growth on a limiting sulfate concentration, while SulP1 and SulP2 appear to be low-affinity sulfate transporters. ModABC is the sole high-affinity molybdate transport system and is essential for growth with NO3(-) as a nitrogen source on limiting levels of molybdate (<0.25 MUM). However, at 2.5 MUM molybdate, a quadruple mutant with all four transporters inactivated, had the longest lag phase on NO3(-), suggesting these systems all make some contribution to molybdate transport. Growth of Rlv3841 on limiting levels of sulfate increased sulB, sulP1, modB, and sulP2 expression 313.3-, 114.7-, 6.2-, and 4.0-fold, respectively, while molybdate starvation increased only modB expression (three- to 7.5-fold). When grown in high-sulfate but not low-sulfate medium, pea plants inoculated with LMB695 (modB) reduced acetylene at only 14% of the wild-type rate, and this was not further reduced in the quadruple mutant. Overall, while modB is crucial to nitrogen fixation at limiting molybdate levels in the presence of sulfate, there is an unidentified molybdate transporter also capable of sulfate transport. PMID- 26812046 TI - Analysis of Fluorescence Lifetime and Energy Transfer Efficiency in Single Molecule Photon Trajectories of Fast-Folding Proteins. AB - In single-molecule Forster resonance energy transfer (FRET) spectroscopy, the dynamics of molecular processes are usually determined by analyzing the fluorescence intensity of donor and acceptor dyes. Since FRET efficiency is related to fluorescence lifetimes, additional information can be extracted by analyzing fluorescence intensity and lifetime together. For fast processes where individual states are not well separated in a trajectory, it is not easy to obtain the lifetime information. Here, we present analysis methods to utilize fluorescence lifetime information from single-molecule FRET experiments, and apply these methods to three fast-folding, two-state proteins. By constructing 2D FRET efficiency-lifetime histograms, the correlation can be visualized between the FRET efficiency and fluorescence lifetimes in the presence of the submicrosecond to millisecond dynamics. We extend the previously developed method for analyzing delay times of donor photons to include acceptor delay times. To determine the kinetics and lifetime parameters accurately, we used a maximum likelihood method. We found that acceptor blinking can lead to inaccurate parameters in the donor delay time analysis. This problem can be solved by incorporating acceptor blinking into a model. While the analysis of acceptor delay times is not affected by acceptor blinking, it is more sensitive to the shape of the delay time distribution resulting from a broad conformational distribution in the unfolded state. PMID- 26812047 TI - Epidemiology of Epidemic Ebola Virus Disease in Conakry and Surrounding Prefectures, Guinea, 2014-2015. AB - In 2014, Ebola virus disease (EVD) in West Africa was first reported during March in 3 southeastern prefectures in Guinea; from there, the disease rapidly spread across West Africa. We describe the epidemiology of EVD cases reported in Guinea's capital, Conakry, and 4 surrounding prefectures (Coyah, Dubreka, Forecariah, and Kindia), encompassing a full year of the epidemic. A total of 1,355 EVD cases, representing ~40% of cases reported in Guinea, originated from these areas. Overall, Forecariah had the highest cumulative incidence (4* higher than that in Conakry). Case-fatality percentage ranged from 40% in Conakry to 60% in Kindia. Cumulative incidence was slightly higher among male than female residents, although incidences by prefecture and commune differed by sex. Over the course of the year, Conakry and neighboring prefectures became the EVD epicenter in Guinea. PMID- 26812048 TI - Usefulness of Mesoporous Silica as a Template for the Preparation of Bundles of Bi Nanowires with Precisely Controlled Diameter Below 10 nm. AB - The reduction of the diameter of Bi nanowires below 10 nm has been an important target because of the theoretical prediction with regard to significant enhancement in thermoelectric performance by size reduction. In this study, we have demonstrated the usefulness of mesoporous silica with tunable pore size as a template for the preparation of thin Bi nanowires with diameters below 10 nm. Bi was deposited within the templates through a liquid phase deposition using hexane and 1,1,3,3-tetramethyldisiloxane as a solvent and reducing agent, respectively. Bundles of thin Bi nanowires with non-crystalline frameworks were successfully obtained after the template removal. The diameter was precisely controlled between about 6 nm and 9 nm. The judicious choices of mesoporous silica and deposition conditions are critical for the successful preparation. The reliable formation of such thin Bi nanowires reported here opens up exciting new possibilities. PMID- 26812049 TI - Passive Smoke Exposure and Its Effects on Cognition, Sleep, and Health Outcomes in Overweight and Obese Children. AB - BACKGROUND: Passive smoke exposure (PSE) may be a risk factor for childhood overweight and obesity and is associated with worse neurocognitive development, cognition, and sleep in children. The purpose of the study is to examine the effects of PSE on adiposity, cognition, and sleep in overweight and obese children using an objective measure of PSE. METHODS: Overweight or obese children (n = 222) aged 7-11 (9.4 +/- 1.1 years; 58% black; 58% female; 85% obese) were recruited from schools near Augusta, Georgia, over the course of the school year from 2003-2006 for a clinical trial, with data analyzed in 2009-2010. Passive smoke exposure was measured with plasma cotinine. Health, cognitive, and sleep measures and parent report of smoke exposure were obtained. RESULTS: Overweight and obese children with PSE had greater overall and central adiposity than nonexposed overweight and obese children (p < 0.03). However, PSE was unrelated to prediabetes, insulin resistance, or visceral fat. PSE was linked to poorer cognitive scores (p < 0.04) independent of adiposity, but was not related to sleep-disordered breathing. CONCLUSIONS: PSE is associated with fatness and poorer cognition in children. Tailored interventions that target multiple health risk factors including nutrition, physical activity, and tobacco use in children and families are needed to prevent adverse health outcomes related to tobacco use and obesity. PMID- 26812050 TI - Etoricoxib in ankylosing spondylitis: is there a role for active patients refractory to traditional NSAIDs? AB - OBJECTIVES: To evaluate the efficacy of etoricoxib in patients with axial ankylosing spondyloarthritis (AS) refractory to traditional NSAIDs. METHODS: This was an open label, multicentric, randomised, prospective (4 weeks with and open extension to 6 months), non-controlled study. Consecutive patients with axial AS refractory to traditional NSAID eligible for anti-TNF-alpha therapy were selected. The primary outcomes were the rate of patients with good clinical response (not eligible for anti-TNF-alpha therapy after etoricoxib) and the Assessment of Spondyloarthritis International Society response criteria for biologic therapies (ASASBIO) response at 4 weeks. Secondary outcomes included: ASAS20 and 40 responses, ASDAS-CRP response, BASDAI, BASFI, back and night back pain, global patient and physician assessment of the disease, and biologic parameters like C-reactive protein (CRP) at 2, 4 weeks and 6 months. RESULTS: A total of 57 axial AS patients were recruited, 46 men, with mean age of 43 years. After 4 weeks of treatment, 26 patients (46%) achieved a good clinical response and 11 (20%) an ASASBIO response. These results at 24 weeks were 19 (33%) and 13 (23%) respectively. All individual clinical variables improved significantly after 4 weeks of treatment. CRP serum levels decreased after 4 weeks but reached no statistical significance, although 30% of patients showed a normalisation of CRP. CONCLUSIONS: Etoricoxib provided a clear clinical improvement in around a third of patients with axial AS refractory to traditional NSAIDs. Special care should be required when deciding to start anti-TNF-alpha therapy; it seems reasonable to keep in mind these results of etoricoxib treatment. PMID- 26812051 TI - Tanzawaic Acids, a Chemically Novel Set of Bacterial Conjugation Inhibitors. AB - Bacterial conjugation is the main mechanism for the dissemination of multiple antibiotic resistance in human pathogens. This dissemination could be controlled by molecules that interfere with the conjugation process. A search for conjugation inhibitors among a collection of 1,632 natural compounds, identified tanzawaic acids A and B as best hits. They specially inhibited IncW and IncFII conjugative systems, including plasmids mobilized by them. Plasmids belonging to IncFI, IncI, IncL/M, IncX and IncH incompatibility groups were targeted to a lesser extent, whereas IncN and IncP plasmids were unaffected. Tanzawaic acids showed reduced toxicity in bacterial, fungal or human cells, when compared to synthetic conjugation inhibitors, opening the possibility of their deployment in complex environments, including natural settings relevant for antibiotic resistance dissemination. PMID- 26812053 TI - Selection of Treatment Strategies among Patients with Type 2 Diabetes Mellitus in Malaysia: A Grounded Theory Approach. AB - BACKGROUND: Diabetes Mellitus is a multifaceted chronic illness and its life-long treatment process requires patients to continuously engage with the healthcare system. The understanding of how patients manoeuvre through the healthcare system for treatment is crucial in assisting them to optimise their disease management. This study aims to explore issues determining patients' treatment strategies and the process of patients manoeuvring through the current healthcare system in selecting their choice of treatment for T2DM. METHODS: The Grounded Theory methodology was used. Twelve patients with Type 2 Diabetes Mellitus, nine family members and five healthcare providers from the primary care clinics were interviewed using a semi-structured interview guide. Three focus group discussions were conducted among thirteen healthcare providers from public primary care clinics. Both purposive and theoretical samplings were used for data collection. The interviews were audio-taped and transcribed verbatim, followed by line-by-line coding and constant comparison to identify the categories and core category. RESULTS: The concept of "experimentation" was observed in patients' help-seeking behaviour. The "experimentation" process required triggers, followed by information seeking related to treatment characteristics from trusted family members, friends and healthcare providers to enable decisions to be made on the choice of treatment modalities. The whole process was dynamic and iterative through interaction with the healthcare system. The decision-making process in choosing the types of treatment was complex with an element of trial-and-error. The anchor of this process was the desire to fulfil the patient's expected outcome. CONCLUSION: Patients with Type 2 Diabetes Mellitus continuously used "experimentation" in their treatment strategies and help-seeking process. The "experimentation" process was experiential, with continuous evaluation, information seeking and decision-making tinged with the element of trial-and error. The theoretical model generated from this study is abstract, is believed to have a broad applicability to other diseases, may be applied at varying stages of disease development and is non-context specific. PMID- 26812052 TI - Effects of Prednisolone on Disease Progression in Antiretroviral-Untreated HIV Infection: A 2-Year Randomized, Double-Blind Placebo-Controlled Clinical Trial. AB - BACKGROUND: HIV-disease progression correlates with immune activation. Here we investigated whether corticosteroid treatment can attenuate HIV disease progression in antiretroviral-untreated patients. METHODS: Double-blind, placebo controlled randomized clinical trial including 326 HIV-patients in a resource limited setting in Tanzania (clinicaltrials.gov NCT01299948). Inclusion criteria were a CD4 count above 300 cells/MUl, the absence of AIDS-defining symptoms and an ART-naive therapy status. Study participants received 5 mg prednisolone per day or placebo for 2 years. Primary endpoint was time to progression to an AIDS defining condition or to a CD4-count below 200 cells/MUl. RESULTS: No significant change in progression towards the primary endpoint was observed in the intent-to treat (ITT) analysis (19 cases with prednisolone versus 28 cases with placebo, p = 0.1407). In a per-protocol (PP)-analysis, 13 versus 24 study participants progressed to the primary study endpoint (p = 0.0741). Secondary endpoints: Prednisolone-treatment decreased immune activation (sCD14, suPAR, CD38/HLA DR/CD8+) and increased CD4-counts (+77.42 +/- 5.70 cells/MUl compared to -37.42 +/- 10.77 cells/MUl under placebo, p < 0.0001). Treatment with prednisolone was associated with a 3.2-fold increase in HIV viral load (p < 0.0001). In a post-hoc analysis stratifying for sex, females treated with prednisolone progressed significantly slower to the primary study endpoint than females treated with placebo (ITT-analysis: 11 versus 21 cases, p = 0.0567; PP-analysis: 5 versus 18 cases, p = 0.0051): No changes in disease progression were observed in men. CONCLUSIONS: This study could not detect any significant effects of prednisolone on disease progression in antiretroviral-untreated HIV infection within the intent-to-treat population. However, significant effects were observed on CD4 counts, immune activation and HIV viral load. This study contributes to a better understanding of the role of immune activation in the pathogenesis of HIV infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT01299948. PMID- 26812054 TI - Evidence for Community Transmission of Community-Associated but Not Health-Care Associated Methicillin-Resistant Staphylococcus Aureus Strains Linked to Social and Material Deprivation: Spatial Analysis of Cross-sectional Data. AB - BACKGROUND: Identifying and tackling the social determinants of infectious diseases has become a public health priority following the recognition that individuals with lower socioeconomic status are disproportionately affected by infectious diseases. In many parts of the world, epidemiologically and genotypically defined community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged to become frequent causes of hospital infection. The aim of this study was to use spatial models with adjustment for area-level hospital attendance to determine the transmission niche of genotypically defined CA- and health-care-associated (HA)-MRSA strains across a diverse region of South East London and to explore a potential link between MRSA carriage and markers of social and material deprivation. METHODS AND FINDINGS: This study involved spatial analysis of cross-sectional data linked with all MRSA isolates identified by three National Health Service (NHS) microbiology laboratories between 1 November 2011 and 29 February 2012. The cohort of hospital-based NHS microbiology diagnostic services serves 867,254 usual residents in the Lambeth, Southwark, and Lewisham boroughs in South East London, United Kingdom (UK). Isolates were classified as HA- or CA-MRSA based on whole genome sequencing. All MRSA cases identified over 4 mo within the three borough catchment area (n = 471) were mapped to small geographies and linked to area-level aggregated socioeconomic and demographic data. Disease mapping and ecological regression models were used to infer the most likely transmission niches for each MRSA genetic classification and to describe the spatial epidemiology of MRSA in relation to social determinants. Specifically, we aimed to identify demographic and socioeconomic population traits that explain cross area extra variation in HA- and CA-MRSA relative risks following adjustment for hospital attendance data. We explored the potential for associations with the English Indices of Deprivation 2010 (including the Index of Multiple Deprivation and several deprivation domains and subdomains) and the 2011 England and Wales census demographic and socioeconomic indicators (including numbers of households by deprivation dimension) and indicators of population health. Both CA-and HA MRSA were associated with household deprivation (CA-MRSA relative risk [RR]: 1.72 [1.03-2.94]; HA-MRSA RR: 1.57 [1.06-2.33]), which was correlated with hospital attendance (Pearson correlation coefficient [PCC] = 0.76). HA-MRSA was also associated with poor health (RR: 1.10 [1.01-1.19]) and residence in communal care homes (RR: 1.24 [1.12-1.37]), whereas CA-MRSA was linked with household overcrowding (RR: 1.58 [1.04-2.41]) and wider barriers, which represent a combined score for household overcrowding, low income, and homelessness (RR: 1.76 [1.16-2.70]). CA-MRSA was also associated with recent immigration to the UK (RR: 1.77 [1.19-2.66]). For the area-level variation in RR for CA-MRSA, 28.67% was attributable to the spatial arrangement of target geographies, compared with only 0.09% for HA-MRSA. An advantage to our study is that it provided a representative sample of usual residents receiving care in the catchment areas. A limitation is that relationships apparent in aggregated data analyses cannot be assumed to operate at the individual level. CONCLUSIONS: There was no evidence of community transmission of HA-MRSA strains, implying that HA-MRSA cases identified in the community originate from the hospital reservoir and are maintained by frequent attendance at health care facilities. In contrast, there was a high risk of CA MRSA in deprived areas linked with overcrowding, homelessness, low income, and recent immigration to the UK, which was not explainable by health care exposure. Furthermore, areas adjacent to these deprived areas were themselves at greater risk of CA-MRSA, indicating community transmission of CA-MRSA. This ongoing community transmission could lead to CA-MRSA becoming the dominant strain types carried by patients admitted to hospital, particularly if successful hospital based MRSA infection control programmes are maintained. These results suggest that community infection control programmes targeting transmission of CA-MRSA will be required to control MRSA in both the community and hospital. These epidemiological changes will also have implications for effectiveness of risk factor-based hospital admission MRSA screening programmes. PMID- 26812055 TI - Effect of Ozone Treatment on Deoxynivalenol and Wheat Quality. AB - Deoxynivalenol (DON) is a secondary metabolite produced by Fusarium fungi, which is found in a wide range of agricultural products, especially in wheat, barley, oat and corn. In this study, the distribution of DON in the wheat kernel and the effect of exposure time to ozone on DON detoxification were investigated. A high concentration of toxin was found in the outer part of the kernel, and DON was injected from the outside to the inside. The degradation rates of DON were 26.40%, 39.16%, and 53.48% after the samples were exposed to 75 mg/L ozone for 30, 60, and 90 min, respectively. The effect of ozonation on wheat flour quality and nutrition was also evaluated. No significant differences (P > 0.05) were found in protein content, fatty acid value, amino acid content, starch content, carbonyl and carboxyl content, and swelling power of ozone-treated samples. Moreover, the ozone-treated samples exhibited higher tenacity and whiteness, as well as lower extensibility and yellowness. This finding indicated that ozone treatment can simultaneously reduce DON levels and improve flour quality. PMID- 26812056 TI - Mixture Effects of Estrogenic Pesticides at the Human Estrogen Receptor alpha and beta. AB - Consumers of fruits and vegetables are frequently exposed to small amounts of hormonally active pesticides, some of them sharing a common mode of action such as the activation of the human estrogen receptor alpha (hERalpha) or beta (hERbeta). Therefore, it is of particular importance to evaluate risks emanating from chemical mixtures, in which the individual pesticides are present at human relevant concentrations, below their corresponding maximum residue levels. Binary and ternary iso-effective mixtures of estrogenic pesticides at effect concentrations eliciting a 1 or 10% effect in the presence or absence of 17beta estradiol were tested experimentally at the hERalpha in the yeast-based estrogen screen (YES) assay as well as in the human U2-OS cell-based ERalpha chemical activated luciferase gene expression (ERalpha CALUX) assay and at the hERbeta in the ERbeta CALUX assay. The outcome was then compared to predictions calculated by means of concentration addition. In most cases, additive effects were observed with the tested combinations in all three test systems, an observation that supports the need to expand the risk assessment of pesticides and consider cumulative risk assessment. An additional testing of mixture effects at the hERbeta showed that most test substances being active at the hERalpha could also elicit additive effects at the hERbeta, but the hERbeta was less sensitive. In conclusion, effects of the same ligands at the hERalpha and the hERbeta could influence the estrogenic outcome under physiological conditions. PMID- 26812058 TI - A Big Five facet analysis of a psychopath: The validity of the HDS mischievous scale of sub-clinical psychopathy. AB - Around 5,700 British adults completed the NEO-PI-R, which measures the Big Five Personality factors at the Domain and the Facet level, as well as the Hogan Development Survey (HDS); measure of Anti-Social Personality Disorder called Mischievous. Previous work in this field has used clinical measures of psychopathy and either student or patient samples. This sought to validate this measure by comparing NEO facet correlational results with other studies. The Mischievous score from the HDS was the criterion variable in the correlations and multiple regressions. Mischievous people were Disagreeable, Stable, Extraverts, lacking in Conscientiousness. Facet analysis showed them high on Excitement seeking but low of Straightforwardness, Anxiety and Deliberation. Limitations are of the study are discussed. PMID- 26812057 TI - Epidemiology of Birth Defects Based on a Birth Defect Surveillance System from 2005 to 2014 in Hunan Province, China. AB - OBJECTIVE: To describe the epidemiology of birth defects (BDs) in perinatal infants in Hunan Province, China, between 2005 and 2014. METHODS: The BD surveillance data of perinatal infants (for stillbirth, dead fetus or live birth between 28 weeks of gestation and 7 days after birth) were collected from 52 registered hospitals of Hunan between 2005 and 2014. The prevalence rates of BDs with 95% confidence interval (CI) and crude odds ratio (ORs) were calculated to examine the associations of infant gender, maternal age, and region (urban vs rural) with BDs. RESULTS: From 2005 to 2014, there were a total of 925413 perinatal infants of which 17753 had BDs, with the average prevalence of 191.84 per 10000 PIs (perinatal infants), showing a significant uptrend. The risks of BDs are higher in urban areas versus rural areas (OR = 1.20), in male infants versus female infants (OR = 1.19), and in mothers above age 35 versus those below age 35 (OR = 1.24). The main five types of BDs are Congenital heart defects (CHD), Other malformation of external ear (OMEE), Polydactyly, Congenital malformation of kidney (CMK), and Congenital talipes equinovarus (CTE). From 2005 to 2014, the prevalence rates (per 10000 PIs) of CHD and CMK increased significantly from 22.56 to 74 (OR = 3.29, 95%CI: 2.65-4.11) and from 7.61 to 14.62 (OR = 1.92, 95%CI:1.30-2.84), respectively; the prevalence rates of congenital hydrocephalus and neural tube defects (NTDs) decreased significantly from 11.8 to 5.29 (OR = 0.45, 95%CI: 0.31-0.65) and from 7.87 to 1.74 (OR = 0.22, 95%CI: 0.13-0.38), respectively. CONCLUSIONS: The prevalence rates of specific BDs in perinatal infants in Hunan have changed in the last decade. Urban pregnant women, male perinatal infants, and mothers above age 35 present different prevalence rates of BDs. Wider use of new diagnosis technology, improving the ability of monitoring, strengthening the publicity and education are important to reduce the prevalence of BDs. PMID- 26812059 TI - Editorial. PMID- 26812061 TI - Detection of 549 new HLA alleles in potential stem cell donors from the United States, Poland and Germany. AB - We characterized 549 new human leukocyte antigen (HLA) class I and class II alleles found in newly registered stem cell donors as a result of high-throughput HLA typing. New alleles include 101 HLA-A, 132 HLA-B, 105 HLA-C, 2 HLA-DRB1, 89 HLA-DQB1 and 120 HLA-DPB1 alleles. Mainly, new alleles comprised single nucleotide variations when compared with homologous sequences. We identified nonsynonymous nucleotide mutations in 70.7% of all new alleles, synonymous variations in 26.4% and nonsense substitutions in 2.9% (null alleles). Some new alleles (55, 10.0%) were found multiple times, HLA-DPB1 alleles being the most frequent among these. Furthermore, as several new alleles were identified in individuals from ethnic minority groups, the relevance of recruiting donors belonging to such groups and the importance of ethnicity data collection in donor centers and registries is highlighted. PMID- 26812060 TI - Innate lymphoid cells and the MHC. AB - Innate lymphoid cells (ILCs) are a new class of immune cells that include natural killer (NK) cells and appear to be the innate counterparts to CD4(+) helper T cells and CD8(+) cytotoxic T cells based on developmental and functional similarities. Like T cells, both NK cells and other ILCs also show connections to the major histocompatibility complex (MHC). In human and mouse, NK cells recognize and respond to classical and nonclassical MHC I molecules as well as structural homologues, whereas mouse ILCs have recently been shown to express MHC II. We describe the history of MHC I recognition by NK cells and discuss emerging roles for MHC II expression by ILC subsets, making comparisons between both mouse and human when possible. PMID- 26812062 TI - Identification of a novel HLA-A*02 variant, HLA-A*02:586, in a Taiwanese bone marrow hematopoietic stem cell donor. AB - One nucleotide substitution at residue 179 of the HLA-A*02:07:01 results in a new allele, HLA-A*02:586. PMID- 26812063 TI - A novel HLA-DRB1 allele, DRB1*15:66:02 was identified in a Chinese potential donor by sequence-based typing. AB - DRB1*15:66:02 differs from DRB1*15:66:01 at codons 57 and 58 resulting in no coding change. PMID- 26812064 TI - Comparison of the Abilities of SD-OCT and SS-OCT in Evaluating the Thickness of the Macular Inner Retinal Layer for Glaucoma Diagnosis. AB - PURPOSE: To compare the abilities of spectral-domain optical coherence tomography (OCT) (SD-OCT; Spectralis, Heidelberg Engineering) and swept-source OCT (SS-OCT; DRI-OCT1 Atlantis system, Topcon) for analyzing the macular inner retinal layers in diagnosing glaucoma. METHODS: The study included 60 patients with primary open angle glaucoma (POAG) and 60 healthy control subjects. Macular cube area was scanned using SD-OCT and SS-OCT on the same day to assess the thicknesses of the macular retinal nerve fiber layer (mRNFL), ganglion cell layer plus inner plexiform layer (GCIPL), and total retinal layer in nine subfields defined by the Early Treatment Diabetic Retinopathy Study (ETDRS). The abilities of the parameters to discriminate between the POAG and control groups were assessed using areas under the receiver operating characteristic curves (AUCs). RESULTS: Glaucoma-associated mRNFL and GCIPL thinning was more common in the outer zones than inner zones for both SD-OCT and SS-OCT. The mRNFL and GCIPL measurements showed distinct pattern differences between SD-OCT and SS-OCT in each ETDRS subfield. Although the glaucoma-diagnosis ability was comparable between SD-OCT and SS-OCT for most of the parameters, AUC was significantly larger for SD-OCT measurements of the GCIPL thickness in the outer temporal zones (p = 0.003) and of the mRNFL thickness in the outer nasal zones (p = 0.001), with the former having the largest AUC for discriminating POAG from healthy eyes (AUC = 0.894). CONCLUSION: Spectralis SD-OCT and DRI SS-OCT have similar glaucoma-diagnosis abilities based on macular inner layer thickness analysis. However, Spectralis SD OCT was potentially superior to DRI SS-OCT in detecting GCIPL thinning in the outer temporal zone, where the glaucomatous damage predominantly occurs. PMID- 26812065 TI - Burden of Liver Disease among Community-Based People Who Inject Drugs (PWID) in Chennai, India. AB - BACKGROUND AND OBJECTIVE: We characterize the burden of liver disease in a cohort of PWID in Chennai, India, with a high prevalence of HCV. MATERIALS AND METHODS: 1,042 PWID were sampled through community outreach in Chennai. Participants underwent fasting blood draw, questionnaire and an examination that included liver stiffness assessment using transient elastography (Fibroscan) and assessment of steatosis via ultrasound. RESULTS: The median age was 39 years, all were male, 14.8% were HIV infected and 35.6% were HCV antibody positive, of whom 78.9% were chronically infected (HCV RNA positive). Median liver stiffness was 6.2 kPA; 72.9% had no evidence of or mild stiffness, 14.5% had moderate stiffness, and 12.6% had evidence of severe stiffness/cirrhosis. Prevalence of severe stiffness/cirrhosis was significantly higher among persons who were older, had a longer duration of injecting drugs, higher body mass index, higher prevalence of insulin resistance, higher prevalence of steatosis, higher HCV RNA levels and evidence of alcohol dependence. An estimated 42.1% of severe stiffness/cirrhosis in this sample was attributable to HCV. 529 (53.0%) had some evidence of steatosis. Prevalence of steatosis was higher among those who had larger waist circumference, insulin resistance, higher HDL cholesterol and a history of antiretroviral therapy. CONCLUSIONS: We observed a high burden of liver disease in this relatively young cohort that was primarily driven by chronic HCV infection, metabolic factors (insulin resistance and steatosis) and heavy alcohol use. Interventions to improve access to HCV treatment and reduce alcohol use are needed to prevent further progression of liver disease. PMID- 26812067 TI - Pressure-driven semiconducting-semimetallic transition in SnSe. AB - In this work, we report the pressure-dependent electrical transport and structural properties of SnSe. In our experiments an electronic transition from a semiconducting to semimetallic state was observed at 12.6 GPa, followed by an orthorhombic to monoclinic structural transition. Hall effect measurements indicate that both the carrier concentration and mobility vary abnormally accompanied by the semimetallic electronic transition. First-principles band structure calculations confirm the semiconducting-semimetallic transition, and reveal that the semimetallic character of SnSe can be attributed to the enhanced coupling of Sn-5s, Sn-5p, and Se-3p orbitals under compression that results in the broadening of energy bands and subsequently the closure of the band gap. The pressure modulated variations of electrical transport and structural properties may provide an approach to improving the thermoelectric properties of SnSe. PMID- 26812068 TI - Photochemical Behavior of Beryllium Complexes with Subporphyrazines and Subphthalocyanines. AB - Structures of beryllium subphthalocyanines and beryllium subporphyrazines complexes with different substituents are explored for the first time. Their photochemical properties are studied using time-dependent density functional theory calculations and compared to boron-related compounds for which their photochemical activity is already known. These beryllium compounds were found to be thermodynamically stable in a vacuum and present features similar to those of boron-containing analogues, although the nature of bonding between the cation and the macrocycle presents subtle differences. Most important contributions to the main peak in the Q-band region arise from HOMO to LUMO transitions in the case of subphthalocyanines and alkyl subporphyrazine complexes, whereas a mixture of that contribution and a HOMO-2 to LUMO contribution are present in the case of thioalkyl subporphyrazines. The absorption in the visible region could make these candidates suitable for photochemical devices if combined with appropriate donor groups. PMID- 26812066 TI - Discovery of (R)-6-(1-(8-Fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3 a]pyridin-3-yl)ethyl)-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one (AMG 337), a Potent and Selective Inhibitor of MET with High Unbound Target Coverage and Robust In Vivo Antitumor Activity. AB - Deregulation of the receptor tyrosine kinase mesenchymal epithelial transition factor (MET) has been implicated in several human cancers and is an attractive target for small molecule drug discovery. Herein, we report the discovery of compound 23 (AMG 337), which demonstrates nanomolar inhibition of MET kinase activity, desirable preclinical pharmacokinetics, significant inhibition of MET phosphorylation in mice, and robust tumor growth inhibition in a MET-dependent mouse efficacy model. PMID- 26812070 TI - Lipocalin 2 highlights the complex role of neutrophils in alcoholic liver disease. PMID- 26812069 TI - A Miniature Protein Stabilized by a Cation-pi Interaction Network. AB - The design of folded miniature proteins is predicated on establishing noncovalent interactions that direct the self-assembly of discrete thermostable tertiary structures. In this work, we describe how a network of cation-pi interactions present in proteins containing "WSXWS motifs" can be emulated to stabilize the core of a miniature protein. This 19-residue protein sequence recapitulates a set of interdigitated arginine and tryptophan residues that stabilize a distinctive beta-strand:loop:PPII-helix topology. Validation of the compact fold determined by NMR was carried out by mutagenesis of the cation-pi network and by comparison to the corresponding disulfide-bridged structure. These results support the involvement of a coordinated set of cation-pi interactions that stabilize the tertiary structure. PMID- 26812072 TI - Mathematical models and hepatology; oil and vinegar? PMID- 26812071 TI - Single-gene association between GATA-2 and autoimmune hepatitis: A novel genetic insight highlighting immunologic pathways to disease. AB - Background & Aims Autoimmune hepatitis (AIH), an immune-mediated liver disease, originates as a consequence of interacting genetic and environmental risk factors. Treatment remains non-specific and prone to side effects. Deficiencies in regulatory T cell (Treg) function are hypothesized to contribute to the pathogenesis of AIH. Methods We describe an adult patient who presented with AIH in the context of monocytopenia. The patient was characterized by GATA2 gene sequencing, flow cytometry of peripheral blood for leucocyte subsets, ELISA for serum Flt-3 ligand, and immunohistochemistry of liver biopsy tissue. Results Sequencing confirmed a GATA2 mutation. Peripheral Treg were absent in the context of a preserved total T cell count. Immunostaining for the Treg transcription factor FOXP3 was reduced in liver tissue as compared to a control AIH specimen. There were marked deficiencies in multiple antigen-presenting cell subsets and Flt-3 ligand was elevated. These findings are consistent with previous reports of GATA2 dysfunction. Conclusions The association of a GATA2 mutation with AIH is previously unrecognized. GATA2 encodes a hematopoietic cell transcription factor, and mutations may manifest as monocytopenia, dendritic and B cell deficiencies, myelodysplasia, and immunodeficiency. Tregs may be depleted as in this case. Our findings provide support for the role of Tregs in AIH, complement reports of other deficiencies in T cell regulation causing AIH-like syndromes, and support the rationale of attempting to modulate the Treg axis for the therapeutic benefit of AIH patients. PMID- 26812073 TI - Type 2 diabetes and risk of hospital admission or death for chronic liver diseases. AB - BACKGROUND & AIMS: The impact of type 2 diabetes (T2DM) on hospital admissions and deaths due to common chronic liver diseases (CLDs) is uncertain. Our aim was to investigate associations between T2DM and CLDs in a national retrospective cohort study and to investigate the role of sex and socio-economic status (SES). METHODS: We used International Classification of Disease codes to identify incident alcoholic liver disease (ALD), autoimmune liver disease, haemochromatosis, hepatocellular carcinoma, non-alcoholic fatty liver disease (NAFLD) and viral liver disease from linked diabetes, hospital, cancer and death records for people of 40-89years of age in Scotland 2004-2013. We used quasi Poisson regression to estimate rate ratios (RR). RESULTS: There were 6667 and 33624 first mentions of CLD in hospital, cancer and death records over ~1.8 and 24million person-years in people with and without T2DM, respectively. The most common liver disease was ALD among people without diabetes and was NAFLD among people with T2DM. Age-adjusted RR for T2DM compared to the non-diabetic population (95% confidence intervals) varied between 1.27 (1.04-1.55) for autoimmune liver disease and 5.36 (4.41-6.51) for NAFLD. RRs were lower for men than women and for more compared to less deprived populations for both ALD and NAFLD. CONCLUSIONS: T2DM is associated with increased risk of hospital admission or death for all common CLDs and the strength of the association varies by type of CLD, sex and SES. Increasing prevalence of T2DM is likely to result in increasing burden of all CLDs. PMID- 26812074 TI - Long non-coding RNA DILC regulates liver cancer stem cells via IL-6/STAT3 axis. AB - BACKGROUND & AIMS: Emerging evidence has demonstrated the aberrant expression of long non-coding RNAs (lncRNAs) in various malignancies including HCC. However, the knowledge of cancer stem cell-related lncRNAs remains limited. METHODS: lnc DILC (lncRNA downregulated in liver cancer stem cells (LCSCs)) was identified by microarray and validated by real-time PCR. The role of lnc-DILC in LCSCs was assessed both in vitro and in vivo. Pull down assay and oligoribonucleotides or oligodeoxynucleotides treatment were conducted to evaluate the interaction between lnc-DILC and interleukin-6 (IL-6) promoter. RESULTS: Depletion of lnc DILC markedly enhanced LCSC expansion and facilitated HCC initiation and progression, whereas ectopic expression of lnc-DILC dramatically inhibited LCSC expansion. Mechanistically, lnc-DILC inhibited the autocrine IL-6/STAT3 signaling. The putative binding locus of lnc-DILC within IL-6 promoter was confirmed by pull down assay. Consistently, the oligoribonucleotide mimics and an oligodeoxynucleotide decoy of lnc-DILC abrogated the effects on IL-6 transcription, STAT3 activation and LCSC expansion triggered by lnc-DILC depletion and lnc-DILC overexpression. Moreover, our data suggested that lnc-DILC mediated the crosstalk between TNF-alpha/NF-kappaB signaling and IL-6/STAT3 cascade. Clinical investigation demonstrated the reduction of lnc-DILC in patient HCCs, and suggested the correlation between lnc-DILC levels and IL-6, EpCAM or CD24 expression. Decreased lnc-DILC expression in HCCs predicts early recurrence and short survival of patients, highlighting its prognostic value. CONCLUSIONS: lnc-DILC mediates the crosstalk between TNF-alpha/NF-kappaB signaling and autocrine IL-6/STAT3 cascade and connects hepatic inflammation with LCSC expansion, suggesting that lnc-DILC could be not only a potential prognostic biomarker, but also a possible therapeutic target against LCSCs. PMID- 26812075 TI - Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid. AB - BACKGROUND & AIMS: The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH) and type 2 diabetes, activates FXR. Mouse studies demonstrated that FXR activation by OCA alters hepatic expression of many genes. However, no data are available on the effects of OCA in the human liver. Here we generated gene expression profiles in human precision cut liver slices (hPCLS) after treatment with OCA. METHODS: hPCLS were incubated with OCA for 24 h. Wild type or FXR(-/-) mice received OCA or vehicle by oral gavage for 7 days. RESULTS: Transcriptomic analysis showed that well-known FXR target genes, including NR0B2 (SHP), ABCB11 (BSEP), SLC51A (OSTalpha) and SLC51B (OSTbeta), and ABCB4 (MDR3) are regulated by OCA in hPCLS. Ingenuity pathway analysis confirmed that 'FXR/RXR activation' is the most significantly changed pathway upon OCA treatment. Comparison of gene expression profiles in hPCLS and mouse livers identified 18 common potential FXR targets. ChIP-sequencing in mouse liver confirmed FXR binding to IR1 sequences of Akap13, Cgnl1, Dyrk3, Pdia5, Ppp1r3b and Tbx6. CONCLUSIONS: Our study shows that hPCLS respond to OCA treatment by upregulating well-known FXR target genes, demonstrating its suitability to study FXR-mediated gene regulation. We identified six novel bona-fide FXR target genes in both mouse and human liver. Finally, we discuss a possible explanation for changes in high or low density lipoprotein observed in NASH and primary biliary cholangitis patients treated with OCA based on the genomic expression profile in hPCLS. PMID- 26812076 TI - Reply to 'Genetic and clinical data reinforce the role of GAS6 and TAM receptors in liver fibrosis'. PMID- 26812077 TI - Immunization with the Haemophilus ducreyi trimeric autotransporter adhesin DsrA with alum, CpG or imiquimod generates a persistent humoral immune response that recognizes the bacterial surface. AB - The Ducreyi serum resistance A (DsrA) protein of Haemophilus ducreyi belongs to a large family of multifunctional outer membrane proteins termed trimeric autotransporter adhesins responsible for resistance to the bactericidal activity of human complement (serum resistance), agglutination and adhesion. The ability of DsrA to confer serum resistance and bind extracellular matrix proteins lies in its N-terminal passenger domain. We have previously reported that immunization with a recombinant form of the passenger domain of DsrA, rNT-DsrA, in complete/incomplete Freund's adjuvant, protects against a homologous challenge in swine. We present herein the results of an immunogenicity study in mice aimed at investigating the persistence, type of immune response, and the effect of immunization route and adjuvants on surrogates of protection. Our results indicate that a 20 MUg dose of rNT-DsrA administered with alum elicited antisera with comparable bacterial surface reactivity to that obtained with complete/incomplete Freund's adjuvant. At that dose, high titers and bacterial surface reactivity persisted for 211 days after the first immunization. Administration of rNT-DsrA with CpG or imiquimod as adjuvants elicited a humoral response with similar quantity and quality of antibodies (Abs) as seen with Freund's adjuvant. Furthermore, intramuscular administration of rNT-DsrA elicited high-titer Abs with significantly higher reactivity to the bacterial surface than those obtained with subcutaneous immunization. All rNT-DsrA/adjuvant combinations tested, save CpG, elicited a Th2-type response. Taken together, these findings show that a 20 MUg dose of rNT-DsrA administered with the adjuvants alum, CpG or imiquimod elicits high-quality Abs with reactivity to the bacterial surface that could protect against an H. ducreyi infection. PMID- 26812078 TI - Provider communication and HPV vaccination: The impact of recommendation quality. AB - BACKGROUND: Receiving a healthcare provider's recommendation is a strong predictor of HPV vaccination, but little is known empirically about which types of recommendation are most influential. Thus, we sought to investigate the relationship between recommendation quality and HPV vaccination among U.S. adolescents. METHODS: In 2014, we conducted a national, online survey of 1495 parents of 11-17-year-old adolescents. Parents reported whether providers endorsed HPV vaccination strongly, encouraged same-day vaccination, and discussed cancer prevention. Using an index of these quality indicators, we categorized parents as having received no, low-quality, or high-quality recommendations for HPV vaccination. Separate multivariable logistic regression models assessed associations between recommendation quality and HPV vaccine initiation (>= 1 dose), follow through (3 doses, among initiators), refusal, and delay. RESULTS: Almost half (48%) of parents reported no provider recommendation for HPV vaccination, while 16% received low-quality recommendations and 36% received high quality recommendations. Compared to no recommendation, high-quality recommendations were associated with over nine times the odds of HPV vaccine initiation (23% vs. 74%, OR=9.31, 95% CI, 7.10-12.22) and over three times the odds of follow through (17% vs. 44%, OR=3.82, 95% CI, 2.39-6.11). Low-quality recommendations were more modestly associated with initiation (OR=4.13, 95% CI, 2.99-5.70), but not follow through. Parents who received high- versus low-quality recommendations less often reported HPV vaccine refusal or delay. CONCLUSIONS: High-quality recommendations were strongly associated with HPV vaccination behavior, but only about one-third of parents received them. Interventions are needed to improve not only whether, but how providers recommend HPV vaccination for adolescents. PMID- 26812079 TI - Task Shifting the Management of Non-Communicable Diseases to Nurses in Kibera, Kenya: Does It Work? AB - BACKGROUND: In sub-Saharan Africa there is an increasing need to leverage available health care workers to provide care for non-communicable diseases (NCDs). This study was conducted to evaluate adherence to Medecins Sans Frontieres clinical protocols when the care of five stable NCDs (hypertension, diabetes mellitus type 2, epilepsy, asthma, and sickle cell) was shifted from clinical officers to nurses. METHODS: Descriptive, retrospective review of routinely collected clinic data from two integrated primary health care facilities within an urban informal settlement, Kibera, Nairobi, Kenya (May to August 2014). RESULTS: There were 3,554 consultations (2025 patients); 733 (21%) were by nurses out of which 725 met the inclusion criteria among 616 patients. Hypertension (64%, 397/616) was the most frequent NCD followed by asthma (17%, 106/616) and diabetes mellitus (15%, 95/616). Adherence to screening questions ranged from 65% to 86%, with an average of 69%. Weight and blood pressure measurements were completed in 89% and 96% of those required. Laboratory results were reviewed in 91% of indicated visits. Laboratory testing per NCD protocols was higher in those with hypertension (88%) than diabetes mellitus (67%) upon review. Only 17 (2%) consultations were referred back to clinical officers. CONCLUSION: Nurses are able to adhere to protocols for managing stable NCD patients based on clear and standardized protocols and guidelines, thus paving the way towards task shifting of NCD care to nurses to help relieve the significant healthcare gap in developing countries. PMID- 26812080 TI - Restriction of oral intake during labor: whither are we bound? AB - In 1946, Dr Curtis Mendelson suggested that aspiration during general anesthesia for delivery was avoidable by restricting oral intake during labor. This suggestion proved influential, and restriction of oral intake in labor became the norm. These limitations may contribute to fear and feelings of intimidation among parturients. Modern obstetrics, especially in the setting of advances in obstetric anesthesia, does not mirror the clinical landscape of Mendelson; hence, one is left to question if his findings remain relevant or if they should inform current recommendations. The use of general anesthesia at time of cesarean delivery has seen a remarkable decline with increased use of effective neuraxial analgesia as the standard of care in modern obstetric anesthesia. While the American College of Obstetricians and Gynecologists now endorses clear liquids during labor, current recommendations continue to suggest that solid food intake should be avoided. Recent evidence from a systematic review involving 3130 women in active labor suggests that oral intake should not be restricted in women at low risk of complications, given there were no identified benefits or harms of a liberal diet. Aspiration and other adverse maternal outcomes may be unrelated to oral intake in labor and as such, qualitative measures such as patient satisfaction should be paramount. It is time to reassess the impact of oral intake restriction during labor given the minimal risk of aspiration during labor in the setting of modern obstetric anesthesia practices. PMID- 26812081 TI - Pharmacodynamics of transdermal granisetron in women with nausea and vomiting of pregnancy. AB - BACKGROUND: Limited options exist for women with nausea and vomiting of pregnancy (NVP) who cannot tolerate oral intake. Transdermal delivery of granisetron, a 5 hydroxytryptamine-3 receptor antagonist, provides an effective alternative for such patients. OBJECTIVE: The objective of this study was to evaluate the pharmacodynamics of granisetron administered intravenously (IV) and as a sustained release transdermal patch in women with NVP. STUDY DESIGN: We recruited 16 women with singleton gestation between 12 0/7-18 6/7 weeks who were receiving treatment for NVP and had a Pregnancy Unique Quantification of Emesis and Nausea (PUQE) score of >=6. All consenting subjects received 1 mg of granisetron as an IV infusion over 5 minutes and blood was obtained prior to the infusion and at 10, 20, 30, and 60 minutes and at 2, 4, 6, 8, 12, and 24 hours after the start of the infusion. After a minimum washout of 48 hours after initiation of IV granisetron, a 52-cm(2) granisetron patch (34.3 mg) was placed on the upper arm of all subjects for 7 days. Blood was drawn prior to patch placement and daily thereafter for 9 days. The subjects were evaluated daily. The PUQE score was obtained from these subjects prior to the IV infusion and daily for 2 days after and again prior to and daily for 9 days after patch placement. RESULTS: Complete data were available in 15 women after IV administration and 13 women after patch placement. One woman stopped participation during the IV infusion while data were not available in 2 additional women after patch placement due to noncompliance. Peak plasma granisetron concentrations after IV and transdermal administration were similar (~10 ng/mL). Prior to IV administration of granisetron, the PUQE score was 8.6 +/- 1.8 (mean +/- SD). The PUQE scores were significantly reduced for the ensuing 2 days (P < .01). The PUQE score prior to patch placement was 7.6 +/- 2.4. Scores were significantly (P < .001) reduced within 1 day of patch placement and stayed significantly reduced during the ensuing 6 days of patch placement. The patch was removed on the seventh day and PUQE scores increased significantly on the third day after patch removal. No serious side effects were reported either during IV administration or patch placement. CONCLUSION: Granisetron significantly improved symptoms of nausea and vomiting as gauged by the PUQE score. After IV infusion the reduction in PUQE score was observed within 1 day. When granisetron was administered as a patch, benefit likewise was seen within 1 day suggesting rapid absorption of the medication transdermally. The beneficial effect of transdermal granisetron on the PUQE score persisted for the entire 7 days during which the patch was in place. In this small cohort, the granisetron patch appeared to be efficacious in reducing the symptoms of nausea and vomiting. The patch provides another option for treating this disorder and may be particularly useful in women who cannot tolerate oral medications. PMID- 26812082 TI - A DFT-based toxicity QSAR study of aromatic hydrocarbons to Vibrio fischeri: Consideration of aqueous freely dissolved concentration. AB - In the present study, quantitative structure-activity relationship (QSAR) techniques based on toxicity mechanism and density functional theory (DFT) descriptors were adopted to develop predictive models for the toxicity of alkylated and parent aromatic hydrocarbons to Vibrio fischeri. The acute toxicity data of 17 aromatic hydrocarbons from both literature and our experimental results were used to construct QSAR models by partial least squares (PLS) analysis. With consideration of the toxicity process, the partition of aromatic hydrocarbons between water phase and lipid phase and their interaction with the target biomolecule, the optimal QSAR model was obtained by introducing aqueous freely dissolved concentration. The high statistical values of R(2) (0.956) and Q(CUM)(2) (0.942) indicated that the model has good goodness-of-fit, robustness and internal predictive power. The average molecular polarizability (alpha) and several selected thermodynamic parameters reflecting the intermolecular interactions played important roles in the partition of aromatic hydrocarbons between the water phase and biomembrane. Energy of the highest occupied molecular orbital (E(HOMO)) was the most influential descriptor which dominated the toxicity of aromatic hydrocarbons through the electron-transfer reaction with biomolecules. The results demonstrated that the adoption of freely dissolved concentration instead of nominal concentration was a beneficial attempt for toxicity QSAR modeling of hydrophobic organic chemicals. PMID- 26812083 TI - Environmentally-friendly in situ plated bismuth-film electrode for the quantification of the endocrine disruptor parathion in skimmed milk. AB - An in situ bismuth-film electrode (BiFE) together with square-wave cathodic voltammetry (SWCV) was used to determine the concentration of the endocrine disruptor parathion in skimmed milk. The experimental conditions (deposition time, deposition potential and Bi (III) concentration) were optimized for the preparation of the BiFE. A glassy carbon electrode was used as the substrate. The selection of the chemical composition of the supporting electrolyte and the solution pH was aimed at improving the reduction of parathion at the BiFE surface. In addition, the parameters of the square-wave cathodic voltammetry were adjusted to improve the sensor performance. A cathodic current identified at 0.523 V increased linearly with the parathion concentration in the range of 0.2 2.0 MUmol L(-1) (R=0.999). The sensitivity of the calibration curve obtained was 4.09 MUA L MUmol(-1), and the limits of detection (LOD) and quantification (LOQ) were 55.7 nmol L(-1) and 169.0 nmol L(-1), respectively. The performance of the sensor was tested using a sample of skimmed milk with parathion added. The same determination was carried out by UV-vis spectroscopy and the results obtained were used for the statistical evaluation of the data obtained. PMID- 26812084 TI - Case study and lessons learned from the ammonium nitrate explosion at the West Fertilizer facility. AB - In West, Texas on April 17, 2013, a chemical storage and distribution facility caught fire followed by the explosion of around 30 tons of ammonium nitrate while the emergency responders were trying to extinguish the fire, leading to 15 fatalities and numerous buildings, businesses and homes destroyed or damaged. This incident resulted in devastating consequences for the community around the facility, and shed light on a need to improve the safety management of local small businesses similar to the West facility. As no official report on the findings of the incident has been released yet, this article first investigates the root causes of the incident, and presents a simplified consequence analysis. The article reviews the regulations applicable to this type of facility and recommended emergency response procedures to identify gaps between what happened in West and the current regulations, and discusses how the current regulations could be modified to prevent or minimize future losses. Finally, the federal response that followed the incident until the publication of this paper is summarized. PMID- 26812085 TI - Cdc42 and k-Ras Control Endothelial Tubulogenesis through Apical Membrane and Cytoskeletal Polarization: Novel Stimulatory Roles for GTPase Effectors, the Small GTPases, Rac2 and Rap1b, and Inhibitory Influence of Arhgap31 and Rasa1. AB - A critical and understudied property of endothelial cells is their ability to form lumens and tube networks. Although considerable information has been obtained concerning these issues, including the role of Cdc42 and Rac1 and their effectors such as Pak2, Pak4, Par6b, and co-regulators such as integrins, MT1-MMP and Par3; many key questions remain that are necessary to elucidate molecular and signaling requirements for this fundamental process. In this work, we identify new small GTPase regulators of EC tubulogenesis including k-Ras, Rac2 and Rap1b that act in conjunction with Cdc42 as well as the key downstream effectors, IQGAP1, MRCKbeta, beta-Pix, GIT1, and Rasip1 (which can assemble into multiprotein complexes with key regulators including alpha2beta1 integrin and MT1 MMP). In addition, we identify the negative regulators, Arhgap31 (by inactivating Cdc42 and Rac) and Rasa1 (by inactivating k-Ras) and the positive regulator, Arhgap29 (by inactivating RhoA) which play a major functional role during the EC tubulogenic process. Human EC siRNA suppression or mouse knockout of Rasip1 leads to identical phenotypes where ECs form extensive cord networks, but cannot generate lumens or tubes. Essential roles for these molecules during EC tubulogenesis include; i) establishment of asymmetric EC cytoskeletal polarization (subapical distribution of acetylated tubulin and basal membrane distribution of F-actin); and ii) directed membrane trafficking of pinocytic vacuoles or other intracellular vesicles along acetylated tubulin tracks to the developing apical membrane surface. Cdc42 co-localizes subapically with acetylated tubulin, while Rac1 and k-Ras strongly label vacuole/ vesicle membranes which accumulate and fuse together in a polarized, perinuclear manner. We observe polarized apical membrane and subapical accumulation of key GTPases and effectors regulating EC lumen formation including Cdc42, Rac1, Rac2, k-Ras, Rap1b, activated c-Raf and Rasip1 to control EC tube network assembly. Overall, this work defines novel key regulators and their functional roles during human EC tubulogenesis. PMID- 26812086 TI - Computationally Guided Identification of Novel Mycobacterium tuberculosis GlmU Inhibitory Leads, Their Optimization, and in Vitro Validation. AB - Mycobacterium tuberculosis (Mtb) infections are causing serious health concerns worldwide. Antituberculosis drug resistance threatens the current therapies and causes further need to develop effective antituberculosis therapy. GlmU represents an interesting target for developing novel Mtb drug candidates. It is a bifunctional acetyltransferase/uridyltransferase enzyme that catalyzes the biosynthesis of UDP-N-acetyl-glucosamine (UDP-GlcNAc) from glucosamine-1 phosphate (GlcN-1-P). UDP-GlcNAc is a substrate for the biosynthesis of lipopolysaccharide and peptidoglycan that are constituents of the bacterial cell wall. In the current study, structure and ligand based computational models were developed and rationally applied to screen a drug-like compound repository of 20,000 compounds procured from ChemBridge DIVERSet database for the identification of probable inhibitors of Mtb GlmU. The in vitro evaluation of the in silico identified inhibitor candidates resulted in the identification of 15 inhibitory leads of this target. Literature search of these leads through SciFinder and their similarity analysis with the PubChem training data set (AID 1376) revealed the structural novelty of these hits with respect to Mtb GlmU. IC50 of the most potent identified inhibitory lead (5810599) was found to be 9.018 +/- 0.04 MUM. Molecular dynamics (MD) simulation of this inhibitory lead (5810599) in complex with protein affirms the stability of the lead within the binding pocket and also emphasizes on the key interactive residues for further designing. Binding site analysis of the acetyltransferase pocket with respect to the identified structural moieties provides a thorough analysis for carrying out the lead optimization studies. PMID- 26812087 TI - Redox regulation in the thylakoid lumen. AB - Higher plants need to balance the efficiency of light energy absorption and dissipative photo-protection when exposed to fluctuations in light quantity and quality. This aim is partially realized through redox regulation within the chloroplast, which occurs in all chloroplast compartments except the envelope intermembrane space. In contrast to the chloroplast stroma, less attention has been paid to the thylakoid lumen, an inner, continuous space enclosed by the thylakoid membrane in which redox regulation is also essential for photosystem biogenesis and function. This sub-organelle compartment contains at least 80 lumenal proteins, more than 30 of which are known to contain disulfide bonds. Thioredoxins (Trx) in the chloroplast stroma are photo-reduced in the light, transferring reducing power to the proteins in the thylakoid membrane and ultimately the lumen through a trans-thylakoid membrane-reduced, equivalent pathway. The discovery of lumenal thiol oxidoreductase highlights the importance of the redox regulation network in the lumen for controlling disulfide bond formation, which is responsible for protein activity and folding and even plays a role in photo-protection. In addition, many lumenal members involved in photosystem assembly and non-photochemical quenching are likely required for reduction and/or oxidation to maintain their proper efficiency upon changes in light intensity. In light of recent findings, this review summarizes the multiple redox processes that occur in the thylakoid lumen in great detail, highlighting the essential auxiliary roles of lumenal proteins under fluctuating light conditions. PMID- 26812089 TI - How Accurate Is the Pulse Oximeter, and Does It Matter. PMID- 26812088 TI - Seed priming to alleviate salinity stress in germinating seeds. AB - Salinity is one of the major abiotic stresses that affect crop production in arid and semiarid areas. Seed germination and seedling growth are the stages most sensitive to salinity. Salt stress causes adverse physiological and biochemical changes in germinating seeds. It can affect the seed germination and stand establishment through osmotic stress, ion-specific effects and oxidative stress. The salinity delays or prevents the seed germination through various factors, such as a reduction in water availability, changes in the mobilization of stored reserves and affecting the structural organization of proteins. Various techniques can improve emergence and stand establishment under salt conditions. One of the most frequently utilized is seed priming. The process of seed priming involves prior exposure to an abiotic stress, making a seed more resistant to future exposure. Seed priming stimulates the pre-germination metabolic processes and makes the seed ready for radicle protrusion. It increases the antioxidant system activity and the repair of membranes. These changes promote seed vigor during germination and emergence under salinity stress. The aim of this paper is to review the recent literature on the response of plants to seed priming under salinity stress. The mechanism of the effect of salinity on seed germination is discussed and the seed priming process is summarized. Physiological, biochemical and molecular changes induced by priming that lead to seed enhancement are covered. Plants' responses to some priming agents under salinity stress are reported based on the best available data. For a great number of crops, little information exists and further research is needed. PMID- 26812090 TI - Manganese Compounds as Water-Oxidizing Catalysts: From the Natural Water Oxidizing Complex to Nanosized Manganese Oxide Structures. AB - All cyanobacteria, algae, and plants use a similar water-oxidizing catalyst for water oxidation. This catalyst is housed in Photosystem II, a membrane-protein complex that functions as a light-driven water oxidase in oxygenic photosynthesis. Water oxidation is also an important reaction in artificial photosynthesis because it has the potential to provide cheap electrons from water for hydrogen production or for the reduction of carbon dioxide on an industrial scale. The water-oxidizing complex of Photosystem II is a Mn-Ca cluster that oxidizes water with a low overpotential and high turnover frequency number of up to 25-90 molecules of O2 released per second. In this Review, we discuss the atomic structure of the Mn-Ca cluster of the Photosystem II water-oxidizing complex from the viewpoint that the underlying mechanism can be informative when designing artificial water-oxidizing catalysts. This is followed by consideration of functional Mn-based model complexes for water oxidation and the issue of Mn complexes decomposing to Mn oxide. We then provide a detailed assessment of the chemistry of Mn oxides by considering how their bulk and nanoscale properties contribute to their effectiveness as water-oxidizing catalysts. PMID- 26812091 TI - Comparative Assessment of Glycosylation of a Recombinant Human FSH and a Highly Purified FSH Extracted from Human Urine. AB - Glycosylation is an important PTM and is critical for the manufacture and efficacy of therapeutic glycoproteins. Glycan significantly influences the biological properties of human follicle-stimulating hormone (hFSH). Using a glycoproteomic strategy, this study compared the glycosylation of a putative highly purified FSH (uhFSH) obtained from human urine with that of a recombinant human FSH (rhFSH) obtained from Chinese hamster ovary (CHO) cells. Intact and subunit masses, N-glycans, N-glycosylation sites, and intact N- and O glycopeptides were analyzed and compared by mass spectrometry. Classic and complementary analytical methods, including SDS-PAGE, isoelectric focusing, and the Steelman-Pohley bioassay were also employed to compare their intact molecular weights, charge variants, and specific activities. Results showed that highly sialylated, branched, and macro-heterogeneity glycans are predominant in the uhFSH compared with those in rhFSH. The O-glycopeptides of both hFSHs, which have not been described previously, were characterized herein. A high degree of heterogeneity was observed in the N-glycopeptides of both hFSHs. The differences in glycosylation provide useful information in elucidating and in further investigation the critical glycan structures of hFSH. PMID- 26812092 TI - Using the folding landscapes of proteins to understand protein function. AB - Proteins fold on a biologically-relevant timescale because of a funnel-shaped energy landscape. This landscape is sculpted through evolution by selecting amino acid sequences that stabilize native interactions while suppressing stable non native interactions that occur during folding. However, there is strong evolutionary selection for functional residues and these cannot be chosen to optimize folding. Their presence impacts the folding energy landscape in a variety of ways. Here, we survey the effects of functional residues on folding by providing several examples. We then review how such effects can be detected computationally and be used as assays for protein function. Overall, an understanding of how functional residues modulate folding should provide insights into the design of natural proteins and their homeostasis. PMID- 26812093 TI - Depopulation of Single-Phthalocyanine Molecular Orbitals upon Pyrrolic-Hydrogen Abstraction on Graphene. AB - Single-molecule chemistry with a scanning tunneling microscope has preponderantly been performed on metal surfaces. The molecule-metal hybridization, however, is often detrimental to genuine molecular properties and obscures their changes upon chemical reactions. We used graphene on Ir(111) to reduce the coupling between Ir(111) and adsorbed phthalocyanine molecules. By local electron injection from the tip of a scanning tunneling microscope the two pyrrolic H atoms were removed from single phthalocyanines. The detachment of the H atom pair induced a strong modification of the molecular electronic structure, albeit with no change in the adsorption geometry. Spectra and maps of the differential conductance combined with density functional calculations unveiled the entire depopulation of the highest occupied molecular orbital upon H abstraction. Occupied pi states of intact molecules are proposed to be emptied via intramolecular electron transfer to dangling sigma states of H-free N atoms. PMID- 26812094 TI - Quality and Safety Education for Nurses (QSEN): The Key is Systems Thinking. AB - Over a decade has passed since the Institute of Medicine's reports on the need to improve the American healthcare system, and yet only slight improvement in quality and safety has been reported. The Quality and Safety Education for Nurses (QSEN) initiative was developed to integrate quality and safety competencies into nursing education. The current challenge is for nurses to move beyond the application of QSEN competencies to individual patients and families and incorporate systems thinking in quality and safety education and healthcare delivery. This article provides a history of QSEN and proposes a framework in which systems thinking is a critical aspect in the application of the QSEN competencies. We provide examples of how using this framework expands nursing focus from individual care to care of the system and propose ways to teach and measure systems thinking. The conclusion calls for movement from personal effort and individual care to a focus on care of the system that will accelerate improvement of healthcare quality and safety. PMID- 26812095 TI - The Influence of Quality Improvement Efforts on Patient Outcomes And Nursing Work: A Perspective from Chief Nursing Officers at Three Large Health Systems. AB - Quality and performance improvement initiatives are driving significant changes in the United States healthcare system. In anticipation of the full implementation of national health reform over the next several years, the pace of these changes has been increasing. The goals of these quality initiatives mirror the National Quality Strategy's three aims which developed out of the Institute for Healthcare Improvement's triple aim of improving the patient care experience, improving the population's health, and reducing healthcare costs. Projects are underway across the United States to achieve these aims. In this article, Chief Nursing Officers of three of the nation's largest healthcare systems, the Department of Veterans Affairs, Kaiser Permanente, and Ascension Health, have outlined their organizations' quality and performance improvement initiatives. Their forward-thinking projects broadly address several aspects of healthcare, including reduction of hospital-acquired conditions, patient engagement, and the integration of mobile technologies and other informatics solutions to improve clinical workflows and increase registered nurses' access to knowledge resources. The article then offers a brief analysis and conclusion of these three exemplars. The projects span the information systems life cycle: some are well established and continuing to improve, others have been recently implemented, and still others planned for implementation in the near future. PMID- 26812096 TI - An Academic Practice Partnership: Helping New Registered Nurses to Advance Quality and Patient Safety. AB - Significant changes in the healthcare environment have occurred that offer challenges for quality improvement and nursing education programs, and thus impact both nursing practice and education. We formed an academic-practice partnership to actively engage students enrolled in an undergraduate nursing research course in quality processes with participation in a medical center's performance improvement program. This article describes the development of the partnership; and projects, results, and implications for practice. Students worked collaboratively in groups with hospital staff performance improvement preceptors and a course faculty member. Using the Plan, Do, Check, Act (PDCA) model, students collected, analyzed, and disseminated data from existing projects, or those for which the organization had identified a need. Leaders involved in the inception of this partnership agreed that it achieved its goals of enabling the college to effectively teach recently mandated quality improvement methodologies to achieve competency and enhancing the medical center's capabilities to obtain data for quality improvement purposes. The academic-practice partnership continues to evolve, and we offer discussion about lessons learned and partnership growth. PMID- 26812097 TI - Building Linkages between Nursing Care and Improved Patient Outcomes: The Role of Health Information Technology. AB - Health information technology (health IT or HIT) holds the potential to transform the quality of care and to establish linkages between nursing care and patient outcomes. This article defines eMeasurement and describes Quality of Care Definitions and Metrics for Evaluation. The authors explore the role of health IT to improve quality, barriers to eMeasurement, and health IT interventions by considering linkages between nursing care and patient outcomes for a select set of nursing sensitive indicators including patient falls, pressure ulcers, and the patient experience. We discuss specific challenges, such as barriers for routine data capture to populate nursing sensitive indicators and the use of health IT to promote positive outcomes. The conclusion addresses the implications of the current state of health IT and identifies areas for further nursing research. PMID- 26812098 TI - An Overview of the National Quality Strategy: Where Do Nurses Fit? AB - The definition of quality healthcare, its accurate measurement, and its effective management is nebulous and constantly evolving. Even the most respected and knowledgeable experts cannot come to consensus on exactly what quality means. Levels of measurement, as well as questions of whom, how, and when to measure are topics of continual deliberation. These discussions occur at multiple levels through councils, committees, workgroups, task forces, and expert panels. Many policy-related decisions these groups make affect nurses and nursing care. All of them affect how patients receive or engage in healthcare. This article discusses the National Quality Strategy by offering a description and history of the quality conversation, including federal advisory committees and quality measurement data standards. There are several gaps in the quality conversation to which nurses could contribute valuable insights. The authors describe ways that nurses can engage in the national quality agenda. The article concludes with a call to action to encourage nurses to take a larger role in driving the National Quality Strategy. PMID- 26812099 TI - Electronic Health Record: Driving Evidence-Based Catheter-Associated Urinary Tract Infections (CAUTI) Care Practices. AB - Catheter-associated urinary tract infections (CAUTIs) continue to account for most hospital-acquired infections; yet records for up to 50% of hospitalized patients who received an indwelling catheter lack documentation of evidence-based criterion for the insertion decision. Newer guidelines emphasize prevention of infection by limiting both catheter use and duration of use so as to decrease the number of hospital-acquired, urinary tract infections (UTIs). In this article, we review the literature and describe the method employed in our quality improvement (QI) project using the electronic health record (EHR) to assist in driving evidence-based care. We developed an infrastructure that provided clinical decision support, drove evidence-based care delivery practices, and maintained sustainability. Next, we present the results of this QI project that demonstrated a significant decrease in positive urine cultures, improved catheter care practices, and documentation of evidence-based criterion for catheter utilization. We discuss the benefits of using the EHR to decrease urinary catheter usage and conclude by recommending the using the EHR to decrease UTIs by limiting urinary catheter usage. PMID- 26812100 TI - Challenges in High Fidelity Simulation: Risk Sensitization and Outcome Measurement. AB - As the use of high fidelity simulation (HFS) in nursing education increases, evidence of its impact on learner self-confidence continues to grow. However, evidence to demonstrate an actual, positive influence on learner competence remains inconsistent. This lack of clear evidence supporting increased clinical competence challenges faculty seeking effective teaching strategies related to HFS. The purpose of this article is to discuss two key challenges in the integration and use of HFS in nursing curricula. The authors review the use of HFS in nursing education and provide a critical discussion of two challenges to incorporating HFS into the nursing curricula: the dangers of risk sensitization and the need for a standardized framework. They conclude that simulation experiences that encompass the element of longitudinal care and patient response, along with further research identifying best practices are needed to provide a sound basis for supporting the use of HFS in nursing education. PMID- 26812101 TI - Ethics: Deactivating a Cardiac Pacemaker: Is it Ethical? PMID- 26812102 TI - Cochrane Review Brief: Exercise Interventions on Health-Related Quality of Life for Cancer Survivors. PMID- 26812103 TI - Cochrane Review Brief: Email for Communicating Results of Diagnostic Medical Investigations to Patients. PMID- 26812104 TI - Cochrane Review Brief: Email for Clinical Communication Between Healthcare Professionals. PMID- 26812105 TI - 4-Hydroxy cinnamic acid as mushroom preservation: Anti-tyrosinase activity kinetics and application. AB - Tyrosinase is a key enzyme in post-harvest browning of fruit and vegetable. To control and inhibit its activity is the most effective method for delaying the browning and extend the shelf life. In this paper, the inhibitory kinetics of 4 hydroxy cinnamic acid on mushroom tyrosinase was investigated using the kinetics method of substrate reaction. The results showed that the inhibition of tyrosinase by 4-hydroxy cinnamic acid was a slow, reversible reaction with fractional remaining activity. The microscopic rate constants were determined for the reaction on 4-hydroxy cinnamic acid with tyrosinase. Furthermore, the molecular docking was used to simulate 4-hydroxy cinnamic acid dock with tyrosinase. The results showed that 4-hydroxy cinnamic acid interacted with the enzyme active site mainly through the hydroxy competed with the substrate hydroxy group. The cytotoxicity study of 4-hydroxy cinnamic acid indicated that it had no effects on the proliferation of normal liver cells. Moreover, the results of effects of 4-hydroxy cinnamic acid on the preservation of mushroom showed that it could delay the mushroom browning. These results provide a comprehensive underlying the inhibitory mechanisms of 4-hydroxy cinnamic acid and its delaying post-harvest browning, that is beneficial for the application of this compound. PMID- 26812106 TI - An overview on the interaction of phenazinium dye phenosafranine to RNA triple and double helices. AB - Triple helical nucleic acids or triplex are formed from the combination of three oligonucleotides. In the double stranded form the base pairs are joined through Watson-Crick base pairing while the third strand of the triplex is joined through Hoogsteen base pairing. The Hoogsteen base paired strands are less stable compare to the Watson-Crick strands. Thus stabilization of the Hoogsteen strand gains importance due to the implication of stable triplexes in various biological processes. For this reason here we have monitored the effect of phenosafranine, a phenazinium dye on the structure of poly(U).poly(A)*poly(U) triplex. Our data revealed that the dye has higher binding affinity to the RNA triplex (K'=3.7 * 10(5) M(-1)) compared to the parent duplex (K'=1.9 * 10(5) M(-1)) form. Through a series of spectroscopic and viscometric study we have found that the dye binds to triplex or duplex through the mechanism of intercalation and it stabilizes the Watson-Crick strand while the Hoogsteen strand remains unaffected. PMID- 26812107 TI - Novel serine keratinase from Caldicoprobacter algeriensis exhibiting outstanding hide dehairing abilities. AB - The current paper reports on the purification of an extracellular thermostable keratinase (KERCA) produced from Caldicoprobacter algeriensis strain TH7C1(T), a thermophilic, anaerobic bacterium isolated from a hydrothermal hot spring in Algeria. The maximum keratinase activity recorded after 24-h of incubation at 50 degrees C was 21000 U/ml. The enzyme was purified by ammonium sulfate precipitation-dialysis and heat treatment (2h at 50 degrees C) followed by UNO Q 6 FPLC anion exchange chromatography, and submitted to biochemical characterization assays. Matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis revealed that the purified enzyme was a monomer with a molecular mass of 33246.10 Da. The sequence of the 23 N-terminal residues of KERCA showed high homology with those of bacterial keratinases. Optimal activity was achieved at pH 7 and 50 degrees C. The enzyme was completely inhibited by phenylmethanesulfonyl fluoride (PMSF) and diiodopropyl fluorophosphates (DFP), which suggests that it belongs to the serine keratinase family. KERCA displayed higher levels of hydrolysis and catalytic efficiency than keratinase KERQ7 from Bacillus tequilensis strain Q7. These properties make KERCA a potential promising and eco-friendly alternative to the conventional chemicals used for the dehairing of goat, sheep, and bovine hides in the leather processing industry. PMID- 26812108 TI - Expression, purification and antibody preparation of PCV2 Rep and ORF3 proteins. AB - Rep and ORF3 proteins are important functional proteins of porcine circovirus 2 (PCV2). Here, Rep and ORF3 genes were cloned, expressed and used to raise polyclonal antibodies. The result showed the recombinant plasmids of Rep and ORF3 genes constructed in this study were expressed efficiently in the prokaryotic system, and the recombinant proteins had antigenicity and immunogenicity. Furthermore, reactivity and specificity of the antiserums were characterized by western blot and indirect immunofluorescent assays. The results elucidated that polyclonal antiserum prepared with Rep or ORF3 had good reactivity and specificity against PCV2, or the Rep and ORF3 expressed in PK-15 cells, respectively. The Rep protein is promising for PCV2 antibody and vaccine development. These results will be helpful for further studies focusing on pathogenesis of PCV2 and serology diagnostic test or vaccine development against PCV2. PMID- 26812109 TI - Existence of hydroxylated MWCNTs demotes the catalysis effect of amylases against starch degradation. AB - Possible interaction between amylase and Multi Walled Carbon Nanotubes (MWCNTs) has been elucidated with spectroscopic methods. Hyperchromism of the UV-visible spectra of amylase-CNT conjugates suggested ground state complex formation between them. On contrary, the decreasing fluorescence emission spectra revealed the fate of quenching mechanism to be static. Stoke shift observed from the synchronous and 3D spectra suggested the possibilities of disturbances to the aromatic micro-environment of amylases by OH-MWCNTS. FTIR and FT-Raman spectra showed alteration in the amide I band, that corresponds to their effect on alpha helical structures. Loss of alpha-helical structures and alteration in the dichroic band again revealed possible conformational change and effect towards the stability of polypeptide backbone structures. In addition, the shift observed in the SPR band and FTIR peaks of CNTs-amylase conjugates suggested possible alteration in their optical and structural properties. On the functional aspect, amylase activity on starch degradation and hydrolysis were found to be decreased in the presence of CNTs. PMID- 26812110 TI - CR-LAAO antileukemic effect against Bcr-Abl(+) cells is mediated by apoptosis and hydrogen peroxide. AB - Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Bcr-Abl tyrosine kinase protein, which confers resistance to apoptosis in leukemic cells. Tyrosine kinase inhibitors (TKIs) are effectively used to treat CML; however, CML patients in the advanced (CML-AP) and chronic (CML-CP) phases of the disease are usually resistant to TKI therapy. Thus, it is necessary to seek for novel agents to treat CML, such as the enzyme l-amino acid oxidase from Calloselasma rhodostoma (CR-LAAO) snake venom. We examined the antitumor effect of CR-LAAO in Bcr-Abl(+) cell lines and peripheral blood mononuclear cells (PBMC) from healthy subjects and CML patients. CR-LAAO was more cytotoxic towards Bcr-Abl(+) cell lines than towards healthy subjects' PBMC. The H2O2 produced during the enzymatic action of CR-LAAO mediated its cytotoxic effect. The CR-LAAO induced apoptosis in Bcr-Abl(+) cells, as detected by caspases 3, 8, and 9 activation, loss of mitochondrial membrane potential, and DNA damage. CR-LAAO elicited apoptosis in PBMC from CML-CP patients without TKI treatment more strongly than in PBMC from healthy subjects and TKI-treated CML-CP and CML-AP patients. The antitumor effect of CR-LAAO against Bcr-Abl(+) cells makes this toxin a promising candidate to CML therapy. PMID- 26812111 TI - The effect of pH on the glucose response of the glucose-galactose binding protein L255C labeled with Acrylodan. AB - The glucose-galactose binding protein (GGBP) is used as an optical biosensor in medical and bioprocess applications. This paper investigates the effect of pH on the behavior of GGBP-L255C labeled with Acrylodan for the purpose of finding the optimum conditions for sensing purposes as well as for protein preparation, purification and storage. The Acrylodan-GGBP fluorescence response in absence and presence of glucose was measured under varying buffer and pH conditions. Dissociation constants (Kd) and Gibbs free energies (DeltaG) for the protein glucose binding were calculated. Binding was found to be energetically favored at slightly acidic to neutral conditions, specifically close to the pI of GBP (~ 5.0). Minimal fluorescence response to glucose was exhibited at pH 3.0 accompanied by a blue shift in the steady state fluorescence spectrum. In contrast, an almost 45% response to glucose was shown at pH 4.5-9.0 with a 13-nm red shift. Frequency domain lifetime measurements and quenching with KI suggest that at highly acidic conditions both the glucose-free and the glucose-bound protein are in a conformation distinct from those observed at higher pH values. PMID- 26812112 TI - Characterization and cytotoxic activity of apoptosis-inducing pierisin-5 protein from white cabbage butterfly. AB - In this study, caspase-dependent apoptosis-inducing pierisin-5 gene was identified and characterized from cabbage white butterfly, Pieris canidia. A thousand-fold increase in expression of pierisin-5 gene was observed from second to third instar larvae, gradually decreasing before pupation. Pierisin-5 was purified from the fifth-instar larvae and was found to exhibit cytotoxicity against HeLa and HepG2 human cancer cell lines. Pierisin-5 showed growth inhibition and several morphological changes such as cell shrinkage, chromatin condensation and apoptotic body formation with programmed cell death in HeLa and HepG2 cells. Moreover, DNA fragmentation was observed after gel electrophoresis analysis. Caspase substrate assay showed further cleavage of Ac-DEVD-pNA, suggesting the activation of Caspase-3. Flow cytometry analysis revealed the cell cycle arrest at G1 phase and increased the percentage of apoptotic cells in cancer cell lines treated with pierisin-5. These findings suggest that pierisin-5 could significantly induce apoptosis in cancer cell lines and is mediated by activation of caspase-3 in the mitochondrial pathway. Phylogenetic analysis using pierisin proteins from Pierid butterflies, ADP-ribosylating toxins from bacteria, human, rat, and mouse indicated the possibility of horizontal transfer of pierisin genes from bacteria to butterflies. The single copy of pierisin gene unlike other insect toxin genes also supports lateral transfer. PMID- 26812113 TI - Development of new phosphated cellulose for application as an efficient biomaterial for the incorporation/release of amitriptyline. AB - In the last years has increased the study about the using of natural biopolymers and theirs derivatives in the removal (adsorption/incorporation) of contaminats of medium aqueous, and theirs utilization in the desorption (release) de drugs. However, there not in the literature studies about the utilization of the cellulose and cellulose phosphate in the adsorption (incorporation)/desorption (release) of the drug amitriptyline (AMI). Therefore, in this study was accomplished the synthesized of the phosphated cellulose (PC) through the reaction of pure cellulose (C) with sodium trimetaphosphate (P) under-reflux, for 4h and at 393K. The efficiency of the reaction was observed by XRD, TG/DTG, (31)P NMR and EDS. The adsorption study for the AMI in aqueous medium was carried out by varying the time, pH, concentration, temperature and ionic strength. The results showed that the PC showed a greater adsorption capacity of AMI than pure cellulose, presenting an increase of about 102.72% in the adsorption capacity of the drug by cellulose after the phosphating reaction. In desorption of drug from the surface of biomaterials was performed by varying the pH and time, where it was observed that PC showed a maximum release of 40.98% +/- 0.31% at pH 7. PMID- 26812114 TI - Covalent binding of hyper-activated Rhizomucor miehei lipase (RML) on hetero functionalized siliceous supports. AB - Physical adsorption onto hydrophobic supports has proven to be an effective way to improve the activity of lipases. Covalent binding, on the other hand, enhances the active lifetime of the immobilized biocatalysts. To combine the benefits of adsorption and covalent binding, immobilization of RML on new hetero-functional supports are reported. For this, chemical modification of silica and silica mesoporous nanoparticles was performed by the simultaneous use of two coupling linkers; Octyltriethoxysilane (OTES) for hydrophobic interaction and glycidoxypropyltrimethoxylsilane (GPTMS) for covalent linkage of RML. Altering the GPTMS/OTES ratio makes possible to have different amount of octyl and epoxy groups on the supports. The results showed that immobilization of RML on octyl functionalized supports produces specific activity almost 1.5-2 folds greater than the specific activity of the free enzyme. The observed hyper-activation decreased with increasing epoxy groups on the supports confirming the enhancement of covalent nature of the attachment. Leaching experiment was also confirmed positive effect of the presence of epoxy groups on the supports. Regarding the specific activity of the immobilized preparations and desorption percentages of RML from each support, the most suitable carrier obtains from the functionalization of the supports in presence of GPTMS and OTES in the ratio of 1:1. PMID- 26812115 TI - Immobilization of papaya laccase in chitosan led to improved multipronged stability and dye discoloration. AB - A purified papaya laccase was immobilized in chitosan beads using entrapment approach and its physico-chemical properties were investigated and compared with that of free enzyme. Increase in properties of the laccase such as optimum temperature (by 10 degrees C), thermostability (by 3-folds) and optimum pH (from 8.0 to 10.0) was observed after immobilization. Immobilization led to increased tolerance of enzyme to a number of metal ions (including heavy metals) and organic solvents namely, ethanol, isopropanol, methanol, benzene and DMF. The catalytic efficiency (Kcat/Km) of the immobilized enzyme was found to increase more than ten folds, in comparison to that of the free enzyme, with hydroquinone as substrate. Immobilization of laccase also led to improvement in dye decolorization such that the synthetic dye indigo carmine (50 MUg/ml) was completely decolorized within 8h of incubation as compared to that of the free laccase which decolorized the same dye to only 56% under similar conditions. Thus, immobilization of laccase into chitosan beads led to tremendous improvement in various useful attributes of this enzyme thereby making it more versatile for its industrial exploitation. PMID- 26812116 TI - Unfolding of insulin at the surface of ZnO quantum dots. AB - ZnO quantum dots (QDs) have been used in many biomedical applications such as bioimaging, cancer treatments and etc. Crystallinity, particle size, optical absorption and photoluminescence spectra of ZnO QDs were analyzed by X-ray diffraction (XRD), transmission electron microscopy (TEM), UV-vis absorption spectroscopy and fluorescence spectroscopy respectively. Interaction of ZnO QDs with insulin was investigated by fluorescence quenching, circular dichroism (CD), isothermal titration calorimetry (ITC) and thermal aggregation tests. The fluorescence quenching results showed a static type quenching along with red shift in synchronize fluorescence (a sign of protein unfolding). CD spectroscopy results also confirmed this unfolding and show a reduction in alpha helices content of insulin in contact with ZnO QDs and their conversion to random coils. According to ITC results, the DeltaG, DeltaH and binding constant of this interaction are -32.35 kJ/mol, -43.21 kJ/mol and 4.69 * 10(5) M(-1), respectively. Thermal aggregation test showed fast aggregation of insulin in the presence of ZnO QDs. Therefore in biological application of ZnO QDs such as bioimaging, presence of such QDs in vicinity of insulin could unfold this protein. PMID- 26812117 TI - Effect of Protonation upon Electronic Coupling in the Mixed Valence and Mixed Protonated Complex, [Ni(2,3-pyrazinedithiol)2]. AB - We demonstrate that protonation of a mixed valence molecule, generating a mixed valence mixed protonated (MVMP) state, results in a severe reduction in the electronic coupling intimately connected with electron transfer kinetics. This phenomenon is illustrated by synthesizing a mixed valence molecule, [Ni(2,3 pyrazinedithiol)2], that can be asymmetrically protonated, rendering the MVMP state. We characterize the structural, electronic, vibrational, and magnetic properties of this complex in five different states, including the mixed valence and MVMP states, and then analyze the intervalence charge transfer (IVCT) band to demonstrate a five-fold reduction in electronic coupling upon protonation. We conclude that the reduction in electronic coupling is a result of the asymmetry of the electronic orbitals of the redox sites that results from the asymmetric protonation. This conclusion suggests that many systems designed to link electron and proton transfer will also exhibit a decrease in electronic coupling upon protonation as the strength of the interaction between redox and protonation sites is increased. PMID- 26812118 TI - Euflammation attenuates peripheral inflammation-induced neuroinflammation and mitigates immune-to-brain signaling. AB - Peripheral inflammation can trigger a number of neuroinflammatory events in the CNS, such as activation of microglia and increases of proinflammatory cytokines. We have previously identified an interesting phenomenon, termed "euflammation", which can be induced by repeated subthreshold infectious challenges. Euflammation causes innate immune alterations without overt neuroimmune activation. In the current study, we examined the protective effect of euflammation against peripheral inflammation-induced neuroinflammation and the underlying mechanisms. When Escherichia coli or lipopolysaccharide (LPS) was injected inside or outside the euflammation induction locus (EIL), sickness behavior, global microglial activation, proinflammatory cytokine production in the brain, expression of endothelial cyclooxygenase II and induction of c-fos expression in the paraventricular nucleus of the hypothalamus were all attenuated in the euflammatory mice compared with those in the control unprimed mice. Euflammation also modulated innate immunity outside the EIL by upregulating receptors for pathogen-associated molecular patterns in spleen cells. In addition, euflammation attenuated CNS activation in response to an intra-airpouch (outside the EIL) injection of LPS without suppressing the cytokine expression in the airpouch. Collectively, our study demonstrates that signaling of peripheral inflammation to the CNS is modulated dynamically by peripheral inflammatory kinetics. Specifically, euflammation can offer effective protection against both bacterial infection and endotoxin induced neuroinflammation. PMID- 26812120 TI - The mitogen-activated protein kinase gene, VdHog1, regulates osmotic stress response, microsclerotia formation and virulence in Verticillium dahliae. AB - The fungus Verticillium dahliae has gained worldwide notoriety as a destructive plant pathogen, causing vascular wilt diseases on diverse plant species. V. dahliae produces melanized resting bodies, known as microsclerotia, which can survive for 15 years in the soil, and are thus critically important in its disease cycle. However, the molecular mechanisms that underpin microsclerotia formation, survival, and germination remain poorly understood. In this study, we observed that deletion of VdHog1 (DeltaVdHog1), encoding a homolog of a high osmolarity glycerol (HOG) response mitogen-activated protein kinase, displayed decreased numbers of melanized microsclerotia in culture, heightened sensitivity to hyperosmotic stress, and increased resistance to the fungicide fludioxonil. Through RNA-Seq analysis, we identified 221 genes differentially expressed in the DeltaVdHog1 strain. Interestingly, the expression levels of genes involved in melanin biosynthesis, as well as the hydrophobin gene VDH1, involved in the early stage of microsclerotia formation, were significantly decreased in the DeltaVdHog1 strains relative to the wild-type expression levels. The DeltaVdHog1 strains exhibited decreased virulence relative to the wild type strain on smoke tree seedlings. These results indicate that VdHog1 regulates hyperosmotic stress responses in V. dahliae, and establishes the Hog1-mediated pathway as a target to further probe the up- and downstream processes that regulate asexual development in this fungus. PMID- 26812122 TI - Drugs for acne. PMID- 26812119 TI - Pro-atherogenic role of smooth muscle Nox4-based NADPH oxidase. AB - Nox4-based NADPH oxidase is a major reactive oxygen species-generating enzyme in the vasculature, but its role in atherosclerosis remains controversial. OBJECTIVE: Our goal was to investigate the role of smooth muscle Nox4 in atherosclerosis. APPROACH AND RESULTS: Atherosclerosis-prone conditions (disturbed blood flow and Western diet) increased Nox4 mRNA level in smooth muscle of arteries. To address whether upregulated smooth muscle Nox4 under atherosclerosis-prone conditions was directly involved in the development of atherosclerosis, mice carrying a human Nox4 P437H dominant negative mutation (Nox4DN), specifically in smooth muscle, were generated on a FVB/N ApoE deficient genetic background to counter the effect of increased smooth muscle Nox4. Nox4DN significantly decreased aortic stiffness and atherosclerotic lesions, with no effect on blood pressure. Gene analysis indicated that soluble epoxide hydrolase 2 (sEH) was significantly downregulated in Nox4DN smooth muscle cells (SMC), at both mRNA and protein levels. Downregulation of sEH by siRNA decreased SMC proliferation and migration, and suppressed inflammation and macrophage adhesion to SMC. CONCLUSIONS: Downregulation of smooth muscle Nox4 inhibits atherosclerosis by suppressing sEH, which, at least in part, accounts for inhibition of SMC proliferation, migration and inflammation. PMID- 26812121 TI - Functional convergence and divergence of mating-type genes fulfilling in Cordyceps militaris. AB - Fungal sexual lives are considerably diversified in terms of the types of mating systems and mating-control gene functions. Sexual fruiting bodies of the ascomycete fungus Cordyceps militaris have been widely consumed as edible and medicinal mushrooms, whereas the regulation of fruiting-body development and sex in this fungus remain elusive. Herein, we performed the comprehensive functional analyses of mating-type (MAT) genes in C. militaris. Interspecies functional convergence was evident that MAT1-1 and MAT1-2-1 null mutants were sterile and lost the ability to produce stromata in outcrosses with the opposite mating-type partner. In contrast to other fungal species, functional divergence of MAT1-1-1 and MAT1-1-2 was also observed that DeltaMAT1-1-1 produced barren stromata in outcrosses, whereas DeltaMAT1-1-2 generated fruiting bodies morphologically similar to that of the parental strain but with sterile perithecia. The homothallic-like transformants MAT1-2::MAT1-1-1 (haploidic MAT1-2 isolate transformed with the MAT1-1-1 gene) produced sterile stromata, whereas the MAT1 1::MAT1-2-1 (haploidic MAT1-1 isolate transformed with the MAT1-2-1 gene) mutant was determined to be completely fruitless. The findings relating to the fully fertile gene-complementation mutants suggest that the genomic location is not essential for the MAT genes to fulfill their functions in C. militaris. Comparison of the production of bioactive constituents cordycepin and adenosine provides experimental support that the fungal sexual cycle is an energy consuming process. The results of the present study enrich our knowledge of both convergent and divergent controls of fungal sex. PMID- 26812123 TI - Drugs for rosacea. PMID- 26812124 TI - Rolapitant (Varubi) for prevention and delayed chemotherapy-induced nausea and vomiting. PMID- 26812125 TI - Mycoplasma pneumoniae Monoclonal P1 Type 2c Outbreak, Russia, 2013. PMID- 26812126 TI - Silicon monoxide--a convenient precursor for large scale synthesis of near infrared emitting monodisperse silicon nanocrystals. AB - While silicon nanocrystals (ncSi) embedded in silicon dioxide thin films have been intensively studied in physics, the potential of batch synthesis of silicon nanocrystals from the solid-state disproportionation of SiO powder has not drawn much attention in chemistry. Herein we describe some remarkable effects observed in the diffraction, microscopy and spectroscopy of SiO powder upon thermal processing in the temperature range 850-1100 degrees C. Quantum confinement effects and structural changes of the material related to the size of the silicon nanocrystals nucleated and grown in this way were established by Photoluminescence (PL), Raman, FTIR and UV-Visible spectroscopy, PXRD and STEM, pinpointing that the most significant disproportionation transformations happened in the temperature range between 900 and 950 degrees C. With this know-how a high yield synthesis was developed that produced polydispersions of decyl-capped, hexane-soluble silicon nanocrystals predominantly with near infrared (NIR) PL. Using size-selective precipitation, these polydispersions were separated into monodisperse fractions, which allowed their PL absolute quantum yield (AQY) to be studied as a function of silicon nanocrystal size. This investigation yielded volcano-shaped plots for the AQY confirming the most efficient PL wavelength for ncSi to be located at around 820-830 nm, which corresponded to a size of 3.5-4.0 nm. This work provides opportunities for applications of size-selected near infrared emitting silicon nanocrystals in biomedical imaging and photothermal therapy. PMID- 26812127 TI - Complete genome sequencing of a recombinant strain between human astrovirus antigen types 2 and 8 isolated from South Korea. AB - Human astroviruses (HAstVs) occur worldwide and are known to the causative agents of diarrhea in infants and elderly patients with immune dysfunction. This study aimed to identify recombinant HAstV strains and characterize rare genotypes. The full-length genome of a recombinant HAstV strain isolated from the stool sample of a patient with acute gastroenteritis from South Korea was amplified using three pairs of previously designed primers and seven newly designed primers. The recombinant HAstV was 6757-bp long and contained three sequential open reading frames (ORFs), designated as ORF1a (2781 bp), ORF1b (1548 bp), and ORF2 (2349 bp). Our findings suggested that a recombination event had occurred between ORF1b and ORF2 of the isolated strain, with a recombination breakpoint at 4081 bp. To our knowledge, this is the first study to reveal the complete nucleotide sequence of a recombinant HAstV strain from South Korea. Our study findings might be useful for identifying other recombinant HAstV strains and for developing vaccines against this pathogenic virus. PMID- 26812128 TI - Whole genome alignment based one-step real-time RT-PCR for universal detection of avian orthoreoviruses of chicken, pheasant and turkey origins. AB - Newly emerging avian orthoreovirus (ARV) variants have been continuously detected in Pennsylvania poultry since 2011. In this paper, we report our recent diagnostic assay development of one-step real-time RT-PCR (rRT-PCR) for the rapid and universal detection of all ARVs or reference strains of chicken, pheasant and turkey origins and six sigmaC genotypes of the newly emerging field ARV variants in Pennsylvania (PA) poultry. Primers and probes for the rRT-PCR were designed from the conserved region of the M1 genome segment 5' end based on the whole genome alignment of various ARV strains, including six field variants or novel strains obtained in PA poultry. The detection limit of the newly developed rRT PCR for ARV was as low as 10 copies/reaction of viral RNA, and 10(0.50)-10(0.88) tissue culture infectious dose (TCID50)/100 MUL of viruses. This new rRT-PCR detected all six sigmaC genotypes from the 66 ARV field variant strains and reference strains tested in this study. There were no cross-reactions with other avian viruses. Reproducibility of the assay was confirmed by intra- and inter assay tests with variability from 0.12% to 2.19%. Sensitivity and specificity of this new rRT-PCR for ARV were achieved at 100% and 88%, respectively, in comparison with virus isolation as the "gold standard" in testing poultry tissue specimen. PMID- 26812129 TI - Antinuclear Antibody-Negative Lupus Nephritis with Full House Nephropathy: A Case Report and Review of the Literature. AB - Lupus nephritis (LN) is a serious and common complication of systemic lupus erythematosus (SLE) that predisposes to significant morbidity and mortality. Studies show that prompt diagnosis and treatment improves patient survival. We present a case of a 49-year-old female with an atypical presentation of LN who initially presented with new-onset hypertension, edema, arthritis, serositis and recently diagnosed leukocytoclastic vasculitis who later developed acute kidney injury, hematuria and nephrotic syndrome. Laboratory testing showed mixed cryoglobulinemia and elevated perinuclear anti-neutrophil cytoplasmic (p-ANCA) and myeloperoxidase (MPO) antibodies. SLE-related serologies were negative. Kidney biopsy showed diffuse proliferative global glomerulonephritis with a full house nephropathy pattern on immunofluorescence suggestive of LN. Due to high clinical suspicion and renal biopsy findings, she was treated for LN with prompt renal response to immunosuppression. Cryoglobulins, p-ANCA and MPO titers normalized and the negative SLE serologies remained negative. Literature review on antinuclear antibody (ANA)-negative and seronegative LN revealed the following patient presentations: (1) renal-limited or renal and extra-renal manifestations of SLE with negative serologies and (2) renal and extra-renal manifestations of SLE with negative serologies at presentation who develop positive serologies later in follow-up. Both groups represent a unique and challenging cohort of patients who may require longer follow-up and further testing to rule out other glomerular diseases that may mimic LN on renal biopsy. The absence of SLE-related serologies should be weighed against a high pre-test probability of ANA-negative or seronegative LN. If highly suspected, the patient should be treated promptly with close monitoring. PMID- 26812130 TI - Supramolecular Fibers in Gels Can Be at Thermodynamic Equilibrium: A Simple Packing Model Reveals Preferential Fibril Formation versus Crystallization. AB - Low molecular weight gelators are able to form nanostructures, typically fibers, which entangle to form gel-phase materials. These materials have wide-ranging applications in biomedicine and nanotechnology. While it is known that supramolecular gels often represent metastable structures due to the restricted molecular dynamics in the gel state, the thermodynamic nature of the nanofibrous structure is not well understood. Clearly, 3D extended structures will be able to form more interactions than 1D structures. However, self-assembling molecules are typically amphiphilic, thus giving rise to a combination of solvophobic and solvophilic moieties where a level of solvent exposure at the nanostructure surface is favorable. In this study, we introduce a simple packing model, based on prisms with faces of different nature (solvophobic and solvophilic) and variable interaction parameters, to represent amphiphile self-assembly. This model demonstrates that by tuning shape and "self" or "solvent" interaction parameters either the 1D fiber or 3D crystal may represent the thermodynamic minimum. The model depends on parameters that relate to features of experimentally known systems: the number of faces exposed to the solvent or buried in the fiber; the overall shape of the prism; and the free energy penalties associated with the interactions can be adjusted to match their chemical nature. The model is applied to describe the pH-dependent gelation/precipitation of well-known gelator Fmoc-FF. We conclude that, despite the fact that most experimentally produced gels probably represent metastable states, one-dimensional fibers can represent thermodynamic equilibrium. This conclusion has critical implications for the theoretical treatment of gels. PMID- 26812131 TI - Population Effects of Influenza A(H1N1) Pandemic among Health Plan Members, San Diego, California, USA, October-December 2009. AB - Lacking population-specific data, activity of seasonal and pandemic influenza is usually tracked by counting the number of diagnoses and visits to medical facilities above a baseline. This type of data does not address the delivery of services in a specific population. To provide population-specific data, this retrospective study of patients with influenza-like illness, influenza, and pneumonia among members of a Kaiser Permanente health plan in San Diego, California, USA, during October-December 2009 was initiated. Population data included the number of outpatients accessing healthcare; the number of patients diagnosed with pneumonia; antimicrobial therapy administered; number of patients hospitalized with influenza, influenza-like illness, or pneumonia; level of care provided; and number of patients requiring specialized treatments (e.g., oxygen, ventilation, vasopressors). The rate of admissions specific to weeks and predictions of 2 epidemiologic models shows the strengths and weaknesses of those tools. Data collected in this study may improve planning for influenza pandemics. PMID- 26812132 TI - Wave propagation in piezoelectric layered structures of film bulk acoustic resonators. AB - In this paper, we studied the wave propagation in a piezoelectric layered plate consisting of a piezoelectric thin film on an electroded elastic substrate with or without a driving electrode. Both plane-strain and anti-plane waves were taken into account for the sake of completeness. Numerical results on dispersion relations, cut-off frequencies and vibration distributions of selected modes were given. The effects of mass ratio of driving electrode layer to film layer on the dispersion curve patterns and cut-off frequencies of the plane-strain waves were discussed in detail. Results show that the mass ratio does not change the trend of dispersion curves but larger mass ratio lowers corresponding frequency at a fixed wave number and may extend the frequency range for energy trapping. Those results are of fundamental importance and can be used as a reference to develop effective two-dimensional plate equations for structural analysis and design of film bulk acoustic resonators. PMID- 26812133 TI - [Pain therapy for acute renal colics: Nonsteroidal anti-inflammatory drugs (NSAIDs) and non-opioids]. PMID- 26812135 TI - Ebola Virus RNA Stability in Human Blood and Urine in West Africa's Environmental Conditions. AB - We evaluated RNA stability of Ebola virus in EDTA blood and urine samples collected from infected patients and stored in West Africa's environmental conditions. In blood, RNA was stable for at least 18 days when initial cycle threshold values were <30, but in urine, RNA degradation occurred more quickly. PMID- 26812136 TI - MicroRNA-9 controls apoptosis of neurons by targeting monocyte chemotactic protein-induced protein 1 expression in rat acute spinal cord injury model. AB - OBJECTIVE: For the purpose of an early identification of intervention targets for acute spinal cord injury (ASCI), we investigated the changes in expression levels of microRNA-9 (miR-9) and MCPIP1 in rat ASCI model. METHOD: A total of 108 healthy rats were randomly divided into non-ASCI group (n=18) and five ASCI groups, 6h, 12h, 24h, 3 days and 7 days, representing the experimental time points following ASCI (n=18 per group). Hematoxylin and eosin (HE) staining was used to assess the ASCI damage, and quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH) were employed for the detection of miR-9 and MCPIP1 mRNA expression. RESULTS: HE staining results showed normal neuronal morphology in the non-ASCI group, but spinal cord tissue at 6h after ASCI showed developing neuronal necrosis. Acute inflammatory response was evident at 12h and 24h, with immune cells infiltrating into the gray matter. Vascular permeability increased and the nerve cells in gray-white matter exhibited extensive damage and necrosis at 24h and 7 days after ASCI. MiR-9 expression in ASCI tissue was significantly lower than that in normal spinal cord tissue. Statistical analysis showed a significant decrease in miR-9 expression in all the ASCI groups, compared to the non-ASCI group. Results from real-time PCR analysis revealed that MCPIP1 expression in all the ASCI groups was significantly higher than the non-ASCI group, and MCPIP1 expressions gradually increased with times at 6h-24h after ASCI. ISH revealed the following results after ASCI (1) miR-9 and MCPIP1 mRNA expression mainly distributed in ventral horn motor neurons, (2) miR-9 expression was high at 7 day after ASCI and (3) in the non-ASCI group, MCPIP1 expression was high at 6h, 12h, 24h and 3 days. CONCLUSION: MCPIP1 is significantly up-regulated after ASCI. The negative relationship between MCPIP1 and miR-9 suggest that MCPIP1 mRNA could be a target of miR-9 during ASCI. Thus, miR-9 is a marker for apoptosis in neurons, and an excellent therapeutic target for ASCI patients. PMID- 26812137 TI - NMR study of the interaction of fluorescent 3-hydroxy-4-pyridinone chelators with DMPC liposomes. AB - In the present study we discuss the interaction of two fluorescent 3-hydroxy-4 pyridinone chelators (MRB7 and MRB8) of different lipophilicities with DMPC liposomes based on the analysis of the shifts of the resonance NMR signals and changes in the translational diffusion of both species. The analysis of the variation of the resonance signals of the chelators indicates that both MRB7 and MRB8 strongly interact with the liposomes and that such interaction occurs through both the fluorophore and the chelating moieties of the chelator's framework. Analysis of the variations in the characteristic resonance signals of the lipid provides evidence that MRB7 is able to reach the hydrophobic zone of the bilayer independent of the chelator concentration. The present results corroborate the fact that ethyl substituents in the amino groups of the xanthene ring and the thiourea link are important for the chelator's ability to diffuse across the lipid bilayer. PMID- 26812134 TI - A holistic view of cancer bioenergetics: mitochondrial function and respiration play fundamental roles in the development and progression of diverse tumors. AB - Since Otto Warburg made the first observation that tumor cells exhibit altered metabolism and bioenergetics in the 1920s, many scientists have tried to further the understanding of tumor bioenergetics. Particularly, in the past decade, the application of the state-of the-art metabolomics and genomics technologies has revealed the remarkable plasticity of tumor metabolism and bioenergetics. Firstly, a wide array of tumor cells have been shown to be able to use not only glucose, but also glutamine for generating cellular energy, reducing power, and metabolic building blocks for biosynthesis. Secondly, many types of cancer cells generate most of their cellular energy via mitochondrial respiration and oxidative phosphorylation. Glutamine is the preferred substrate for oxidative phosphorylation in tumor cells. Thirdly, tumor cells exhibit remarkable versatility in using bioenergetics substrates. Notably, tumor cells can use metabolic substrates donated by stromal cells for cellular energy generation via oxidative phosphorylation. Further, it has been shown that mitochondrial transfer is a critical mechanism for tumor cells with defective mitochondria to restore oxidative phosphorylation. The restoration is necessary for tumor cells to gain tumorigenic and metastatic potential. It is also worth noting that heme is essential for the biogenesis and proper functioning of mitochondrial respiratory chain complexes. Hence, it is not surprising that recent experimental data showed that heme flux and function are elevated in non-small cell lung cancer (NSCLC) cells and that elevated heme function promotes intensified oxygen consumption, thereby fueling tumor cell proliferation and function. Finally, emerging evidence increasingly suggests that clonal evolution and tumor genetic heterogeneity contribute to bioenergetic versatility of tumor cells, as well as tumor recurrence and drug resistance. Although mutations are found only in several metabolic enzymes in tumors, diverse mutations in signaling pathways and networks can cause changes in the expression and activity of metabolic enzymes, which likely enable tumor cells to gain their bioenergetic versatility. A better understanding of tumor bioenergetics should provide a more holistic approach to investigate cancer biology and therapeutics. This review therefore attempts to comprehensively consider and summarize the experimental data supporting our latest view of cancer bioenergetics. PMID- 26812138 TI - Photo-activated CO-releasing molecules (PhotoCORMs) of robust sawhorse scaffolds [MU(2)-OOCR(1), eta(1)-NH2CHR(2)(C = O] OCH3, Ru(I)2CO4]. AB - A class of sawhorse-type ruthenium(i) complexes featuring a stable CORM sphere with diverse carboxylic and amino acid derivatives were synthesized and validated as lead structures for photo-activated CO-releasing molecules (PhotoCORMs). The CO release of these CORMs was triggered by 365 nm UV irradiation. Cell viability studies indicated that 3a and 3f were non-toxic both in the dark and in UV light, making them excellent lead structures for therapeutic CORMs. PMID- 26812139 TI - Evaluation of the accuracy of several symptoms and domains in distinguishing patients diagnosed with fibromyalgia from healthy controls. AB - OBJECTIVES: To assess the discriminative power of several symptoms and domains that may assist in the diagnosis of subjects with Fibromyalgia (FM). METHODS: 79 individuals with FM and 66 healthy controls participated in the study. The potential domains proposed by the American College of Rheumatology (ACR) criteria were considered (Wolfe et al., 1990). Binary logistic regression and area under a ROC curve (AUC) were used to rank the importance of the variables in distinguishing patients from pain-free controls. Z values were then calculated to compare the AUC values obtained for each variable with that which yielded the highest AUC (reference standard). For each measure, the cut-offs that maximise sensitivity and specificity were also calculated. RESULTS: The mean pressure pain threshold (PPT) yielded the highest discriminative power (AUC, 0.991) and was therefore chosen as the reference standard; considering an optimal cut- off <=3.97, it correctly classified 95% of patients and 97% of controls. The discriminative powers of tender point count (cut-off >=9), health-related quality of life (cut-off <=63.27) and vitality (cut-off <=46.97) were as good as that of the reference standard. Finally, items related to physical role and function, body pain, fatigue and memory loss showed adequate discriminative power, although slightly lower than that of the reference. CONCLUSIONS: In addition to pain, health-related quality of life and fatigue/vitality were confirmed as the best predictors of individuals with FM. The study findings indicate that tender point count and especially pressure pain threshold (measured with an algometer) continue to be key issues in the clinical assessment of subjects with FM relative to pain-free controls. PMID- 26812140 TI - Integrated approach to sustain biogas production in anaerobic digestion of chicken manure under recycled utilization of liquid digestate: Dynamics of ammonium accumulation and mitigation control. AB - The dynamics of ammonium accumulation and mitigation control in anaerobic digestion of chicken manure under the recycled utilization of liquid digested slurry were investigated by using an integrated approach in two laboratory-scale semi-continuously stirred tank reactors. In the reactor with direct recycled utilization of the anaerobic digested liquid slurry, total volatilized fatty acids (in CH3COOH) and NH4(+)-N increased from 1600mg/L to 8000mg/L and from 2600mg/L to 5000mg/L, respectively. The daily volumetric biogas production decreased from 1.4+/-0.1L/(L.d) to 0.8+/-0.1L/(L.d) with a reduction efficiency of 43+/-4%. Air stripping was integrated for ammonium mitigation of recycled liquid digested slurry and was shown to effectively reduce the ammonium to 3000mg/L. Correspondingly, the biogas production was recovered back to 1.4+/ 0.1L/(L.d). This indicated the potential of the integration of air stripping for ammonium mitigation in an anaerobic digestion process with liquid digested slurry recirculation. PMID- 26812141 TI - Effective multiple stages continuous acetone-butanol-ethanol fermentation by immobilized bioreactors: Making full use of fresh corn stalk. AB - In order to make full use of the fresh corn stalk, the sugar containing juice was used as the sole substrate for acetone-butanol-ethanol production without any nutrients supplement, and the bagasse after squeezing the juice was used as the immobilized carrier. A total 21.34g/L of ABE was produced in batch cells immobilization system with ABE yield of 0.35g/g. A continuous fermentation containing three stages with immobilized cells was conducted and the effect of dilution rate on fermentation was investigated. As a result, the productivity and ABE solvents concentration reached 0.80g/Lh and 19.93g/L, respectively, when the dilution rate in each stage was 0.12/h (corresponding to a dilution rate of 0.04/h in the whole system). And the long-term operation indicated the continuous multiple stages ABE fermentation process had good stability and showed the great potential in future industrial applications. PMID- 26812142 TI - Theoretical Study of Phosphodiester Hydrolysis and Transesterification Catalyzed by an Unsymmetric Biomimetic Dizinc Complex. AB - Density functional theory calculations have been used to investigate the reaction mechanisms of phosphodiester hydrolysis and transesterification catalyzed by a dinuclear zinc complex of the 2-(N-isopropyl-N-((2-pyridyl)methyl)aminomethyl)-6 (N-(carboxylmethyl)-N-((2-pyridyl)methyl)amino-methyl)-4-methylphenol (IPCPMP) ligand, mimicking the active site of zinc phosphotriesterase. The substrates bis(2,4)-dinitrophenyl phosphate (BDNPP) and 2-hydroxypropyl-p-nitrophenyl phosphate (HPNP) were employed as analogues of DNA and RNA, respectively. A number of different mechanistic proposals were considered, with the active catalyst harboring either one or two hydroxide ions. It is concluded that for both reactions the catalyst has only one hydroxide bound, as this option yields lower overall energy barriers. For BDNPP hydrolysis, it is suggested that the hydroxide acts as the nucleophile in the reaction, attacking the phosphorus center of the substrate. For HPNP transesterification, on the other hand, the hydroxide is proposed to act as a Bronsted base, deprotonating the alcohol moiety of the substrate, which in turn performs the nucleophilic attack. The calculated overall barriers are in good agreement with measured rates. Both reactions are found to proceed by essentially concerted associative mechanisms, and it is demonstrated that two consecutive catalytic cycles need to be considered in order to determine the rate-determining free energy barrier. PMID- 26812144 TI - Overestimation of nanoparticles-induced DNA damage determined by the comet assay. AB - The increasing use of engineered nanoparticles (NPs) in a wide range of commercial products raises concern about the possible risks that NPs pose to human health. Many aspects of the interaction between living cells and NPs are still unclear, and a reliable assessment of NP genotoxicity would be important. One of the most common tests used for genotoxicity is the comet assay, a sensitive method measuring DNA damage in individual cells. The assay was originally developed for soluble molecules, but it is also used in the assessment of genotoxicity of NPs. However, concerns have been raised recently about the reliability of this test in the case of NPs, but no conclusive results have been presented. Using nuclei isolated from human epithelial cells incubated with NPs, we obtained clear evidence of overestimation of NP genotoxicity by the comet assay in the case of CeO2, TiO2, SiO2, and polystyrene NPs. Removal of the NPs in the cytoplasm was effective in eliminating this genotoxicity overestimation (ex post damage) and determining the actual damage produced by the NPs during incubation with the cells (ex ante damage). This method could improve significantly the determination of NP genotoxicity in eukaryotic cells. PMID- 26812143 TI - Molecular Basis of Orb2 Amyloidogenesis and Blockade of Memory Consolidation. AB - Amyloids are ordered protein aggregates that are typically associated with neurodegenerative diseases and cognitive impairment. By contrast, the amyloid like state of the neuronal RNA binding protein Orb2 in Drosophila was recently implicated in memory consolidation, but it remains unclear what features of this functional amyloid-like protein give rise to such diametrically opposed behaviour. Here, using an array of biophysical, cell biological and behavioural assays we have characterized the structural features of Orb2 from the monomer to the amyloid state. Surprisingly, we find that Orb2 shares many structural traits with pathological amyloids, including the intermediate toxic oligomeric species, which can be sequestered in vivo in hetero-oligomers by pathological amyloids. However, unlike pathological amyloids, Orb2 rapidly forms amyloids and its toxic intermediates are extremely transient, indicating that kinetic parameters differentiate this functional amyloid from pathological amyloids. We also observed that a well-known anti-amyloidogenic peptide interferes with long-term memory in Drosophila. These results provide structural insights into how the amyloid-like state of the Orb2 protein can stabilize memory and be nontoxic. They also provide insight into how amyloid-based diseases may affect memory processes. PMID- 26812145 TI - Knee flexion contracture treated with botulinum toxin type A in patients with haemophilia (PWH). AB - INTRODUCTION: Knee flexion contracture (KFC) remains a common complication of haemoarthrosis in children and young adults with haemophilia. If the KFC is not treated properly it produces disability, postural and gait abnormalities. OBJECTIVE: Evaluate the effectiveness of conservative treatment of KFC with Botulinum toxin type A (BTX-A) in PWH. METHODS: Seventeen patients were treated, with 21 affected knees. Mean age was 26 years. The mean follow up was 12 months. We evaluated flexion and KFC pretreatment BTX-A and up to 12 months posttreatment. BTX-A application was in hamstring and calf muscles. To evaluate the function, a questionnaire about different activities was made, and it was checked 3, 6 and 12 months after BTX-A. According to the degree of KFC, knees were divided into 3 groups: Group 1: -10 degrees to -30 degrees (n = 10), Group 2: -31 degrees to -45 degrees (n = 6) Group 3: -46 degrees or more (n = 5). RESULTS: The average KFC improved from -38 degrees to -24 degrees . The improvement was 14 degrees (P < 0.001). The average KFC improvement was 9 degrees in group 1, 17 degrees in group 2, and 23 degrees in group 3. There was a high correlation between the improvement in KFC and the total score of the questionnaire R = 0.77. CONCLUSIONS: Treatment of KFC with BTX-A improves knee related functional activities, with the advantage of being a low-cost procedure and easy to apply. PMID- 26812146 TI - Hospital Preparations for Viral Hemorrhagic Fever Patients and Experience Gained from Admission of an Ebola Patient. AB - The Major Incident Hospital of the University Medical Centre of Utrecht has a longstanding history of preparing for the management of highly pathogenic and infectious organisms. An assessment of the hospital's preparations for an outbreak of viral hemorrhagic fever and its experience during admission of a patient with Ebola virus disease showed that the use of the buddy system, frequent training, and information sessions for staff and their relatives greatly increased the sense of safety and motivation among staff. Differing procedures among ambulance services limited the number of services used for transporting patients. Waste management was the greatest concern, and destruction of waste had to be outsourced. The admission of an Ebola patient proceeded without incident but led to considerable demands on staff. The maximum time allowed for wearing personal protective equipment was 45 minutes to ensure safety, and an additional 20 minutes was needed for recovery. PMID- 26812147 TI - Circulating Microparticles and Coronary Plaque Components Assessed by Virtual Histology Intravascular Ultrasound of the Target Lesion in Patients with Stable Angina. AB - High levels of microparticles (MPs) circulate in the blood of patients with atherosclerotic diseases where they can serve as potential biomarkers of vascular injury and cardiovascular outcome. We used virtual histology intravascular ultrasound (VH-IVUS) to evaluate the relationship between the levels of circulating MPs and the coronary plaque composition in patients with stable angina. We included 35 patients with stable angina (22 men, age 64 +/- 9 years) and a de novo target lesion. Preintervention gray-scale and VH-IVUS analysis was performed across the target lesion. Volumetric analysis was performed over a 10 mm-long segment centered at the minimum luminal site. Blood samples were obtained from the femoral artery before coronary angioplasty. MPs were measured using a solid-phase capture assay from a commercial kit. We divided participants into either a low MPs group or high MPs group based on the median value of MPs. There was no significant difference in baseline characteristics between the groups. The plaque burden and remodeling index were similar between the groups. The presence of VH-IVUS-derived thin-cap fibroatheroma was not different between the groups. The percentage of the necrotic core (NC) was significantly higher in the high MPs group than in the low MPs group, both in planar (17.0 +/- 8.8% vs. 24.1 +/- 6.9%, p = 0.012) and volumetric analyses (17.0 +/- 4.8% vs. 22.1 +/- 4.3%, p = 0.002). Circulating MPs were positively correlated with the percentage of the NC area at the minimal luminal site (r = 0.491, p = 0.003) and the percentage of the NC volume (r = 0.496, p = 0.002). Elevated levels of circulating MPs were associated with the amount of NC in the target lesion in those with stable angina, suggesting a potential role of circulating MPs as a biomarker for detecting unstable plaque in patients with stable angina. PMID- 26812149 TI - Proton Quantization and Vibrational Relaxation in Nonadiabatic Dynamics of Photoinduced Proton-Coupled Electron Transfer in a Solvated Phenol-Amine Complex. AB - Nonadiabatic dynamics simulations of photoinduced proton-coupled electron transfer (PCET) in a phenol-amine complex in solution were performed. The electronic potential energy surfaces were generated on-the-fly with a hybrid quantum mechanical/molecular mechanical approach that described the solute with a multiconfigurational method in a bath of explicit solvent molecules. The transferring hydrogen nucleus was represented as a quantum mechanical wave function calculated with grid-based methods, and surface hopping trajectories were propagated on the adiabatic electron-proton vibronic surfaces. Following photoexcitation to the excited S1 electronic state, the overall decay to the ground vibronic state was found to be comprised of relatively fast decay from a lower proton vibrational state of S1 to a highly excited proton vibrational state of the ground S0 electronic state, followed by vibrational relaxation within the S0 state. Proton transfer can occur either on the highly excited proton vibrational states of S0 due to small environmental fluctuations that shift the delocalized vibrational wave functions or on the low-energy proton vibrational states of S1 due to solvent reorganization that alters the asymmetry of the proton potential and reduces the proton transfer barrier. The isotope effect arising from replacing the transferring hydrogen with deuterium is predicted to be negligible because hydrogen and deuterium behave similarly in both types of proton transfer processes. Although an isotope effect could be observed for other systems, in general the absence of an isotope effect does not imply the absence of proton transfer in photoinduced PCET systems. This computational approach is applicable to a wide range of other photoinduced PCET processes. PMID- 26812148 TI - Bait Preference of Free-Ranging Feral Swine for Delivery of a Novel Toxicant. AB - Invasive feral swine (Sus scrofa) cause extensive damage to agricultural and wildlife resources throughout the United States. Development of sodium nitrite as a new, orally delivered toxicant is underway to provide an additional tool to curtail growth and expansion of feral swine populations. A micro-encapsulation coating around sodium nitrite is used to minimize detection by feral swine and maximize stability for the reactive molecule. To maximize uptake of this toxicant by feral swine, development a bait matrix is needed to 1) protect the micro encapsulation coating so that sodium nitrite remains undetectable to feral swine, 2) achieve a high degree of acceptance by feral swine, and 3) be minimally appealing to non-target species. With these purposes, a field evaluation at 88 sites in south-central Texas was conducted using remote cameras to evaluate preferences by feral swine for several oil-based bait matrices including uncolored peanut paste, black-colored peanut paste, and peanut-based slurry mixed onto whole-kernel corn. These placebo baits were compared to a reference food, whole-kernel corn, known to be readily taken by feral swine (i.e., control). The amount of bait consumed by feral swine was also estimated using remote cameras and grid boards at 5 additional sites. On initial exposure, feral swine showed reduced visitations to the uncolored peanut paste and peanut slurry treatments. This reduced visitation subsided by the end of the treatment period, suggesting that feral swine needed time to accept these bait types. The black-colored peanut paste was visited equally to the control throughout the study, and enough of this matrix was consumed to deliver lethal doses of micro-encapsulated sodium nitrite to most feral swine during 1-2 feeding events. None of the treatment matrices reduced visitations by nontarget species, but feral swine dominated visitations for all matrices. It was concluded that black-colored peanut paste achieved satisfactory preference and consumption by feral swine, and no discernable preference by non-target species, compared to the other treatments. PMID- 26812150 TI - Semiparametric Modeling of Daily Ammonia Levels in Naturally Ventilated Caged-Egg Facilities. AB - Ammonia concentration (AMC) in poultry facilities varies depending on different environmental conditions and management; however, this is a relatively unexplored subject in Colombia (South America). The objective of this study was to model daily AMC variations in a naturally ventilated caged-egg facility using generalized additive models. Four sensor nodes were used to record AMC, temperature, relative humidity and wind speed on a daily basis, with 10 minute intervals for 12 weeks. The following variables were included in the model: Heat index, Wind, Hour, Location, Height of the sensor to the ground level, and Period of manure accumulation. All effects included in the model were highly significant (p<0.001). The AMC was higher during the night and early morning when the wind was not blowing (0.0 m/s) and the heat index was extreme. The average and maximum AMC were 5.94+/-3.83 and 31.70 ppm, respectively. Temperatures above 25 degrees C and humidity greater than 80% increased AMC levels. In naturally ventilated caged egg facilities the daily variations observed in AMC primarily depend on cyclic variations of the environmental conditions and are also affected by litter handling (i.e., removal of the bedding material). PMID- 26812151 TI - Pharmaceutical Industry Off-label Promotion and Self-regulation: A Document Analysis of Off-label Promotion Rulings by the United Kingdom Prescription Medicines Code of Practice Authority 2003-2012. AB - BACKGROUND: European Union law prohibits companies from marketing drugs off label. In the United Kingdom--as in some other European countries, but unlike the United States--industry self-regulatory bodies are tasked with supervising compliance with marketing rules. The objectives of this study were to (1) characterize off-label promotion rulings in the UK compared to the whistleblower initiated cases in the US and (2) shed light on the UK self-regulatory mechanism for detecting, deterring, and sanctioning off-label promotion. METHODS AND FINDINGS: We conducted structured reviews of rulings by the UK self-regulatory authority, the Prescription Medicines Code of Practice Authority (PMCPA), between 2003 and 2012. There were 74 off-label promotion rulings involving 43 companies and 65 drugs. Nineteen companies were ruled in breach more than once, and ten companies were ruled in breach three or more times over the 10-y period. Drawing on a typology previously developed to analyse US whistleblower complaints, we coded and analysed the apparent strategic goals of each off-label marketing scheme and the practices consistent with those alleged goals. 50% of rulings cited efforts to expand drug use to unapproved indications, and 39% and 38% cited efforts to expand beyond approved disease entities and dosing strategies, respectively. The most frequently described promotional tactic was attempts to influence prescribers (n = 72, 97%), using print material (70/72, 97%), for example, advertisements (21/70, 30%). Although rulings cited prescribers as the prime target of off-label promotion, competing companies lodged the majority of complaints (prescriber: n = 16, 22%, versus companies: n = 42, 57%). Unlike US whistleblower complaints, few UK rulings described practices targeting consumers (n = 3, 4%), payers (n = 2, 3%), or company staff (n = 2, 3%). Eight UK rulings (11%) pertaining to six drugs described promotion of the same drug for the same off-label use as was alleged by whistleblowers in the US. However, while the UK cases typically related to only one or a few claims made in printed material, several complaints in the US alleged multifaceted and covert marketing activities. Because this study is limited to PMCPA rulings and whistleblower initiated federal cases, it may offer a partial view of exposed off-label marketing. CONCLUSION: The UK self-regulatory system for exposing marketing violations relies largely on complaints from company outsiders, which may explain why most off-label promotion rulings relate to plainly visible promotional activities such as advertising. This contrasts with the US, where Department of Justice investigations and whistleblower testimony have alleged complex off-label marketing campaigns that remain concealed to company outsiders. UK authorities should consider introducing increased incentives and protections for whistleblowers combined with US-style governmental investigations and meaningful sanctions. UK prescribers should be attentive to, and increasingly report, off label promotion. PMID- 26812152 TI - Trends in Socioeconomic Inequalities in Body Mass Index, Underweight and Obesity among English Children, 2007-2008 to 2011-2012. AB - BACKGROUND: Socioeconomic inequalities in childhood obesity have been reported in most developed countries, with obesity more common in deprived groups. Whether inequalities are found in the prevalence of underweight, the rest of the body mass index (BMI) distribution, or have changed across time is not clear. METHODS AND FINDINGS: The sample comprised 5,027,128 children on entry (4 to 5 years old) and leaving (10 to 11 years) state primary (elementary) school who participated in the National Child Measurement Programme (England, United Kingdom). We used area-level deprivation (Indices of Multiple Deprivation at the lower super output area) as a measure of socioeconomic deprivation. From 2007-2008 to 2011-2012 inequalities in obesity between the most compared to least deprived group increased (from 7.21% to 8.30%; p<0.001), whereas inequalities in the prevalence of underweight (1.50% to 1.21%; p = 0.15) were stable during this period. There were no differences by age group or by sex, but a three-way interaction suggested inequalities in obesity had increased at a faster rate for 10 to 11 year old girls, than 4 to 5 year old boys, (2.03% vs 0.07%; p<0.001 for interaction). Investigating inequalities across the distribution of zBMI showed increases in mean zBMI (0.18 to 0.23, p<0.001) could be attributed to increases in inequalities between the 50th and 75th centiles of BMI. Using the 2011 to 2012 population attributable risk estimates, if inequalities were halved, 14.04% (95% CI 14.00% to 14.07%) of childhood obesity could be avoided. CONCLUSIONS: Socioeconomic inequalities in childhood obesity and zBMI increased in England between 2007-2008 and 2011-2012. Inequalities in the prevalence of underweight did not change. Traditional methods of examining inequalities only at the clinical thresholds of overweight and obesity may have led the magnitude of inequalities in childhood BMI to be underestimated. PMID- 26812153 TI - Deciphering Parameter Sensitivity in the BvgAS Signal Transduction. AB - To understand the switching of different phenotypic phases of Bordetella pertussis, we propose an optimized mathematical framework for signal transduction through BvgAS two-component system. The response of the network output to the sensory input has been demonstrated in steady state. An analysis in terms of local sensitivity amplification characterizes the nature of the molecular switch. The sensitivity analysis of the model parameters within the framework of various correlation coefficients helps to decipher the contribution of the modular structure in signal propagation. Once classified, the model parameters are tuned to generate the behavior of some novel strains using simulated annealing, a stochastic optimization technique. PMID- 26812155 TI - Inserting Thienyl Linkers into Conjugated Molecules for Efficient Multilevel Electronic Memory: A New Understanding of Charge-Trapping in Organic Materials. AB - The practical application of organic memory devices requires low power consumption and reliable device quality. Herein, we report that inserting thienyl units into D-pi-A molecules can improve these parameters by tuning the texture of the film. Theoretical calculations revealed that introducing thienyl pi bridges increased the planarity of the molecular backbone and extended the D-A conjugation. Thus, molecules with more thienyl spacers showed improved stacking and orientation in the film state relative to the substrates. The corresponding sandwiched memory devices showed enhanced ternary memory behavior, with lower threshold voltages and better repeatability. The conductive switching and variation in the performance of the memory devices were interpreted by using an extended-charge-trapping mechanism. Our study suggests that judicious molecular engineering can facilitate control of the orientation of the crystallite in the solid state to achieve superior multilevel memory performance. PMID- 26812156 TI - Correction: "Timed Up & Go": A Screening Tool for Predicting 30-Day Morbidity in Onco-Geriatric Surgical Patients? A Multicenter Cohort Study. PMID- 26812154 TI - Nontuberculous Mycobacterial Disease in Children - Epidemiology, Diagnosis & Management at a Tertiary Center. AB - BACKGROUND: There are limited data on the epidemiology, diagnosis and optimal management of nontuberculous mycobacterial (NTM) disease in children. METHODS: Retrospective cohort study of NTM cases over a 10-year-period at a tertiary referral hospital in Australia. RESULTS: A total of 140 children with NTM disease, including 107 with lymphadenitis and 25 with skin and soft tissue infections (SSTIs), were identified. The estimated incidence of NTM disease was 0.6-1.6 cases / 100,000 children / year; no increasing trend was observed over the study period. Temporal analyses revealed a seasonal incidence cycle around 12 months, with peaks in late winter/spring and troughs in autumn. Mycobacterium avium-complex accounted for most cases (77.8%), followed by Mycobacterium ulcerans (14.4%) and Mycobacterium marinum (3.3%). Polymerase chain reaction testing had higher sensitivity than culture and microscopy for acid-fast bacilli (92.0%, 67.2% and 35.7%, respectively). The majority of lymphadenitis cases underwent surgical excision (97.2%); multiple recurrences in this group were less common in cases treated with clarithromycin and rifampicin compared with clarithromycin alone or no anti-mycobacterial drugs (0% versus 7.1%; OR:0.73). SSTI recurrences were also less common in cases treated with two anti mycobacterial drugs compared with one or none (10.5% versus 33.3%; OR:0.23). CONCLUSIONS: There was seasonal variation in the incidence of NTM disease, analogous to recently published observations in tuberculosis, which have been linked to seasonal variation in vitamin D. Our finding that anti-mycobacterial combination therapy was associated with a reduced risk of recurrences in patients with NTM lymphadenitis or SSTI requires further confirmation in prospective trials. PMID- 26812157 TI - Prolonged Oral Administration of a Pan-Retinoic Acid Receptor Antagonist Inhibits Spermatogenesis in Mice With a Rapid Recovery and Changes in the Expression of Influx and Efflux Transporters. AB - We have previously shown that oral administration of a pan-retinoic acid receptor antagonist in mice daily at 2.5 mg/kg for 4 weeks reversibly inhibited spermatogenesis, with no detectable side effects. To elucidate the lowest dose and the longest dosing regimen that inhibits spermatogenesis but results in complete restoration of fertility upon cessation of administration of the drug, we examined the effects of daily doses as low as 1.0 mg/kg with dosing periods of 4, 8, and 16 weeks. We observed 100% sterility in all regimens, with restoration of fertility upon cessation of the drug treatment even for as long as 16 weeks. There was no change in testosterone levels in these males and the progeny examined from 2 of the recovered males were healthy and fertile, with normal testicular weight and testicular histology. Strikingly, a more rapid recovery, as assessed by mating studies, was observed at the lower dose and longer dosing periods. Insight into possible mechanisms underlying this rapid recovery was obtained at 2 levels. First, histological examination revealed that spermatogenesis was not as severely disrupted at the lower dose and with the longer treatment regimens. Second, gene expression analysis revealed that the more rapid recovery may involve the interplay of ATP-binding cassette efflux and solute carrier influx transporters in the testes. PMID- 26812159 TI - Free IL-15 Is More Abundant Than IL-15 Complexed With Soluble IL-15 Receptor alpha in Murine Serum: Implications for the Mechanism of IL-15 Secretion. AB - IL-15 is a cytokine that is part of the innate immune system, as well as a proposed myokine released from skeletal muscle during physical exercise that mediates many of the positive physiological effects of exercise. Many of the immune functions of IL-15 are mediated by juxtacrine signaling via externalized IL-15 bound to membrane-associated IL-15 receptor-alpha (IL-15Ralpha). Serum and plasma samples also contain measurable concentrations of IL-15, believed to arise from proteolytic cleavage of membrane-associated IL-15/IL-15Ralpha complexes to generate soluble IL-15/IL-15Ralpha species. Here, we validate commercial assays that can distinguish the free form of IL-15 and IL-15/IL-15Ralpha complexes. These assays showed that most (86%) IL-15 in mouse serum resides in the free state, with a minor proportion (14%) residing in complex with IL-15Ralpha. Given the much shorter half-life of free IL-15 compared with IL-15/IL-15Ralpha complexes, these findings cast doubt on the currently accepted model for IL-15 secretion from cleavage of membrane-bound IL-15/IL-15Ralpha and suggest that IL 15 is released as a free molecule by an unknown mechanism. PMID- 26812158 TI - Metabolic Benefit of Chronic Caloric Restriction and Activation of Hypothalamic AGRP/NPY Neurons in Male Mice Is Independent of Ghrelin. AB - Aging is associated with attenuated ghrelin signaling. During aging, chronic caloric restriction (CR) produces health benefits accompanied by enhanced ghrelin production. Ghrelin receptor (GH secretagogue receptor 1a) agonists administered to aging rodents and humans restore the young adult phenotype; therefore, we tested the hypothesis that the metabolic benefits of CR are mediated by endogenous ghrelin. Three month-old male mice lacking ghrelin (Ghrelin-/-) or ghrelin receptor (Ghsr-/-), and their wild-type (WT) littermates were randomly assigned to 2 groups: ad libitum (AL) fed and CR, where 40% food restriction was introduced gradually to allow Ghrelin-/- and Ghsr-/- mice to metabolically adapt and avoid severe hypoglycemia. Twelve months later, plasma ghrelin, metabolic parameters, ambulatory activity, hypothalamic and liver gene expression, as well as body composition were measured. CR increased plasma ghrelin and des-acyl ghrelin concentrations in WT and Ghsr-/- mice. CR of WT, Ghsr-/-, and Ghrelin-/- mice markedly improved metabolic flexibility, enhanced ambulatory activity, and reduced adiposity. Inactivation of Ghrelin or Ghsr had no effect on AL food intake or food anticipatory behavior. In contrast to the widely held belief that endogenous ghrelin regulates food intake, CR increased expression of hypothalamic Agrp and Npy, with reduced expression of Pomc across genotypes. In the AL context, ablation of ghrelin signaling markedly inhibited liver steatosis, which correlated with reduced Ppargamma expression and enhanced Irs2 expression. Although CR and administration of GH secretagogue receptor 1a agonists both benefit the aging phenotype, we conclude the benefits of chronic CR are a consequence of enhanced metabolic flexibility independent of endogenous ghrelin or des-acyl ghrelin signaling. PMID- 26812160 TI - Hematopoietic Stem Cells Transplantation Can Normalize Thyroid Function in a Cystinosis Mouse Model. AB - Hypothyroidism is the most frequent and earliest endocrine complication in cystinosis, a multisystemic lysosomal storage disease caused by defective transmembrane cystine transporter, cystinosin (CTNS gene). We recently demonstrated in Ctns(-/-) mice that altered thyroglobulin biosynthesis associated with endoplasmic reticulum stress, combined with defective lysosomal processing, caused hypothyroidism. In Ctns(-/-) kidney, hematopoietic stem cell (HSC) transplantation provides long-term functional and structural protection. Tissue repair involves transfer of cystinosin-bearing lysosomes from HSCs differentiated as F4/80 macrophages into deficient kidney tubular cells, via tunneling nanotubes that cross basement laminae. Here we evaluated the benefit of HSC transplantation for cystinotic thyroid and investigated the underlying mechanisms. HSC engraftment in Ctns(-/-) thyroid drastically decreased cystine accumulation, normalized the TSH level, and corrected the structure of a large fraction of thyrocytes. In the thyroid microenvironment, HSCs differentiated into a distinct, mixed macrophage/dendritic cell lineage expressing CD45 and major histocompatibility complex II but low CD11b and F4/80. Grafted HSCs closely apposed to follicles and produced tunneling nanotube-like extensions that crossed follicular basement laminae. HSCs themselves further squeezed into follicles, allowing extensive contact with thyrocytes, but did not transdifferentiate into Nkx2.1-expressing cells. Our observations revealed significant differences of basement lamina porosity between the thyroid and kidney and/or intrinsic macrophage invasive properties once in the thyroid microenvironment. The contrast between extensive thyrocyte protection and low HSC abundance at steady state suggests multiple sequential encounters and/or remanent impact. This is the first report demonstrating the potential of HSC transplantation to correct thyroid disease and supports a major multisystemic benefit of stem cell therapy for cystinosis. PMID- 26812161 TI - Gata2 Is a Rheostat for Mesenchymal Stem Cell Fate in Male Mice. AB - Gata2 is a zinc finger transcription factor that is important in hematopoiesis and neuronal development. However, the roles of Gata2 in the mesenchymal lineages are poorly understood. In vitro studies suggest that Gata2 modulates adipocyte differentiation and mesenchymal stem cell (MSC) proliferation. To systematically determine the in vivo functions of Gata2 in the MSC lineage commitment and development, we have generated three mouse models in which Gata2 is specifically deleted in MSCs, adipocytes, or osteoblasts. During the MSC expansion stage, Gata2 promotes proliferation and attenuates differentiation; thereby Gata2 loss in MSCs results in enhanced differentiation of both adipocytes and osteoblasts. During the differentiation stage, Gata2 also plays MSC-independent roles to impede lineage commitment; hence, Gata2 loss in adipocyte or osteoblast lineages also augments adipogenesis and osteoblastogenesis, respectively. These findings reveal Gata2 as a crucial rheostat of MSC fate to control osteoblast and adipocyte lineage development. PMID- 26812163 TI - Association between Polymorphisms in Bitter Taste Receptor Genes and Clinical Features in Korean Asthmatics. AB - BACKGROUND: Bitter taste receptors (TAS2R) in human airway smooth muscle have recently been shown to have an important role in bronchodilation, together with beta2-adrenergic receptors. OBJECT: To evaluate the association between genetic variations in TAS2R and clinical features, including bronchodilator response and asthma control. METHOD: We analyzed the association between single nucleotide polymorphisms (SNPs) of TAS2R10 and TAS2R14 and variables such as demographic data, atopy, duration of disease, and asthma control status, including variables such as asthma control test (ACT) score, percent predicted value of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio, as well as bronchodilator response (BDR), in 721 asthma patients in Korea. RESULT: Three novel SNPs of 633G>A, 645C>A, and -79G>A in TAS2R10 and 3 known SNPs of -815T>C, -1267G>A, and -1897T>C in TAS2R14 were analyzed. Increased BDR was significantly associated with SNPs of -815T>C [OR (95% CI) = 1.88 (1.01 3.49), p = 0.04 ] [J Gen Physiol 2005;125:535-553; Am J Respir Cell Mol Biol 2010;42:373-3812], -1267A>G [OR (95% CI) = 2.07 (1.03-4.15), p = 0.04] and 1897T>C [OR (95% CI) = 3.05 (1.01-9.23), p = 0.04, in a dominant model, and OR = 1.91 (1.08-3.36), p = 0.02, in a codominant model] of the TAS2R14 gene. There was a significant association between -815T>C and a low mean ACT score [OR (95% CI) = 5.84 (1.94-17.61), p = 0.001]. In haplotype analysis, TAC, CAT, and TGT, or TG and CA haplotypes on TAS2R14 were significantly associated with increased BDR; CAT and CA haplotypes were significantly associated with a low ACT score. CONCLUSION: Genetic variations in TAS2Rs may be valuable genetic markers to predict therapeutic response and outcomes in asthma. Further research in an independent cohort is needed. PMID- 26812164 TI - Atherosclerosis in Sjogren's syndrome: evidence, possible mechanisms and knowledge gaps. AB - Inflammation has been associated with higher cardiovascular risk in rheumatic autoimmune diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus. More recently, primary Sjogren's syndrome (pSS) was also demonstrated as an independent risk factor for cardiovascular disease, emerging as a new interesting model to study atherosclerosis in autoimmune diseases. Patients with pSS have a higher prevalence of developing traditional cardiovascular risk factors like hypertension and dyslipidaemia predisposing for endothelial dysfunction and premature atherosclerosis. However, the disease specific mechanisms for premature atherosclerosis in pSS are not fully understood. The aim of this review was to critically analyse the current literature on cardiovascular risks in pSS and to discuss the traditional and disease-associated risk factors. We also suggest possible new mechanisms that should be explored in future research to close the current knowledge gaps on the association of pSS, premature atherosclerosis, and clinical cardiovascular disease. PMID- 26812162 TI - All Hormone-Producing Cell Types of the Pituitary Intermediate and Anterior Lobes Derive From Prop1-Expressing Progenitors. AB - Mutations in PROP1, the most common known cause of combined pituitary hormone deficiency in humans, can result in the progressive loss of all hormones of the pituitary anterior lobe. In mice, Prop1 mutations result in the failure to initiate transcription of Pou1f1 (also known as Pit1) and lack somatotropins, lactotropins, and thyrotropins. The basis for this species difference is unknown. We hypothesized that Prop1 is expressed in a progenitor cell that can develop into all anterior lobe cell types, and not just the somatotropes, thyrotropes, and lactotropes, which are collectively known as the PIT1 lineage. To test this idea, we produced a transgenic Prop1-cre mouse line and conducted lineage-tracing experiments of Prop1-expressing cells. The results reveal that all hormone secreting cell types of both the anterior and intermediate lobes are descended from Prop1-expressing progenitors. The Prop1-cre mice also provide a valuable genetic reagent with a unique spatial and temporal expression for generating tissue-specific gene rearrangements early in pituitary gland development. We also determined that the minimal essential sequences for reliable Prop1 expression lie within 10 kilobases of the mouse gene and demonstrated that human PROP1 can substitute functionally for mouse Prop1. These studies enhance our understanding of the pathophysiology of disease in patients with PROP1 mutations. PMID- 26812165 TI - High Plasma Levels of Galectin-3 Are Associated with Increased Risk for Stroke after Carotid Endarterectomy. AB - BACKGROUND: Galectin-3 (Gal-3) has been suggested to have both pro- and anti atherogenic properties. High plasma Gal-3 levels are associated with increased risk for cardiovascular (CV) death. However, it has so far not been investigated if plasma Gal-3 levels can predict the risk for future stroke in patients suffering from carotid atherosclerosis. The aim of this study was to investigate whether Gal-3 could be used as a marker to predict postoperative cerebrovascular ischemic events among patients who underwent carotid endarterectomy (CEA). METHODS: Plasma samples were obtained from 558 CEA patients and Gal-3 levels were analyzed by the proximity extension assay technique. The Swedish national in patient health register was used to identify postoperative cerebrovascular events during the follow-up period (42.6 +/- 26.2 months). RESULTS: Plasma Gal-3 was increased in patients treated for a symptomatic carotid stenosis (p = 0.013). Patients with Gal-3 levels above the median value had an increased incidence of stroke as shown by Kaplan-Meier curves of event-free survival (p = 0.007). Gal-3 was a predictor of postoperative stroke among women (hazard ratio 15.1, 95% CI 1.3-172.2; p = 0.028) even after correction for traditional CV risk factors. CONCLUSIONS: This study is the first to show that increased plasma levels of Gal 3 can help in predicting the occurrence of postoperative strokes among female subjects who undergo CEA, independently of traditional risk factors for cerebrovascular disease. This finding suggests that Gal-3 could be used as a marker to identify patients in need of intensified postoperative medical care. PMID- 26812166 TI - Correction: Evidence for Centromere Drive in the Holocentric Chromosomes of Caenorhabditis. PMID- 26812167 TI - Cationic Chiral Fluorinated Oxazaborolidines. More Potent, Second-Generation Catalysts for Highly Enantioselective Cycloaddition Reactions. AB - The coordination of chiral ligands to Lewis acid metal derivatives, a useful strategy for enantioselective, electrophilic catalysis, generally leads to a lower level of catalytic activity than that of the original uncomplexed compound. Activation by further attachment of a proton or strong Lewis acid to the complex provides a way to overcome the deactivating effect of a chiral ligand. The research described herein has demonstrated that further enhancement of catalytic activity is possible by the judicious placement of fluorine substituents in the chiral ligand. This approach has led to a new, second-generation family of chiral oxazaborolidinium cationic species which can be used to effect many Diels-Alder reactions in >95% yield and >95% ee using catalyst loadings at the 1-2 mol % level. The easy recovery of the chiral ligand makes the application of these new catalysts especially attractive for large-scale synthesis. PMID- 26812168 TI - The Lewis Lead for Detection of Ventriculoatrial Conduction Type. AB - BACKGROUND: Identification of a possible ventriculoatrial (VA) dissociation in wide QRS complex tachycardias is one of the most reliable criteria for differentiation of tachycardia origin. The Lewis lead has been proposed for detection of atrial activity during ventricular tachycardias. HYPOTHESIS: A modified Lewis-lead-ECG will be superior to the standard-lead ECG for detection of ventriculoatrial conduction during ventricular tachycardia. METHODS: Forty seven patients underwent electrophysiological study, stimulated with a fixed cycle length of 400 ms in the ventricle. During stimulation, a standard-lead ECG and a modified Lewis-lead ECG were recorded. Simultaneously, VA conduction was documented by intracardiac electrograms. Surface ECGs were presented to 6 blinded examiners for VA conduction assessment. RESULTS: Type of VA conduction was correctly diagnosed in significantly more ECGs in the Lewis-lead ECG group (mean, 35.0 [75%]) than in the standard-lead ECG group (mean, 29.2 [62%]; P = 0.045). Ventriculoatrial dissociation also was significantly more often correctly diagnosed in the Lewis-lead ECG group (mean, 17.7 [71%]) than in the standard lead ECG group (mean, 12.7 [49%]; P = 0.014). Interobserver agreement was moderate in both groups (kappa = 0.45 and kappa = 0.49, respectively). CONCLUSIONS: Compared with standard-lead ECG, modified Lewis-lead ECG is associated with significantly improved detection of VA conduction type during fast ventricular pacing and thus may help improve ECG diagnosis. PMID- 26812169 TI - Growth Mechanism and Morphology of Hexagonal Boron Nitride. AB - Hexagonal boron nitride (h-BN) sheet is a structural analogue of graphene, yet its growth mechanism has been rarely studied, as complicated by its binary composition. Here, we reveal an atomistic growth mechanism for the h-BN islands by combining crystal growth theory with comprehensive first-principles calculations. The island shapes preferred by edge equilibrium are found to be inconsistent with experimental facts, which is in contrast to previous common views. Then the growth kinetics is explored by analyzing the diffusion and docking of boron and nitrogen atoms at the edges in a step-by-step manner of the nanoreactor approach. The determined sequence of atom-by-atom accretion reveals a strong kinetic anisotropy of growth. Depending on the chemical potential of constituent elements, it yields the h-BN shapes as equilateral triangles or hexagons, explaining a number of experimental observations and opening a way for the synthesis of quality h-BN with controlled morphology. The richer growth kinetics of h-BN compared to graphene is further extendable to other binary two dimensional materials, notably metal dichalcogenides. PMID- 26812170 TI - Monolayer Doping of Si with Improved Oxidation Resistance. AB - In this article, the functionalization of planar silicon with arsenic- and phosphorus-based azides was investigated. Covalently bonded and well-ordered alkyne-terminated monolayers were prepared from a range of commercially available dialkyne precursors using a well-known thermal hydrosilylation mechanism to form an acetylene-terminated monolayer. The terminal acetylene moieties were further functionalized through the application of copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions between dopant-containing azides and the terminal acetylene groups. The introduction of dopant molecules via this method does not require harsh conditions typically employed in traditional monolayer doping approaches, enabling greater surface coverage with improved resistance toward reoxidation. X-ray photoelectron spectroscopy studies showed successful dialkyne incorporation with minimal Si surface oxidation, and monitoring of the C 1s and N 1s core-level spectra showed successful azide-alkyne cycloaddition. Electrochemical capacitance-voltage measurements showed effective diffusion of the activated dopant atoms into the Si substrates. PMID- 26812171 TI - Ten novel MHC class II alleles identified in cynomolgus macaques of Vietnamese origin. AB - Five Mafa-DPB1, two Mafa-DQB1 and three Mafa-DRB novel alleles are identified in Vietnamese cynomolgus macaques. PMID- 26812172 TI - Diterpenes from the Trunk of Abies holophylla and Their Potential Neuroprotective and Anti-inflammatory Activities. AB - Eleven new abietane-type diterpenes, holophyllins D-N (1-11), and 17 known analogues (12-28), were isolated from a MeOH extract of the trunk of Abies holophylla. The chemical structures of 1-11 were determined through spectroscopic data analysis, including NMR ((1)H and (13)C NMR, DEPT, (1)H-(1)H COSY, HMQC, HMBC, and NOESY) and HRFABMS methods. All isolated compounds (1-28) were evaluated for their cytotoxicity against four human tumor cell lines (A549, SK-OV 3, SK-MEL-2, and HCT-116), for their potential neuroprotective effects through induction of nerve growth factor in C6 glioma cells, and for their effects on nitric oxide levels in lipopolysaccharide-stimulated murine microglia BV2 cells. PMID- 26812173 TI - Mitochondrial Dysfunction Plus High-Sugar Diet Provokes a Metabolic Crisis That Inhibits Growth. AB - The Drosophila mutant tko25t exhibits a deficiency of mitochondrial protein synthesis, leading to a global insufficiency of respiration and oxidative phosphorylation. This entrains an organismal phenotype of developmental delay and sensitivity to seizures induced by mechanical stress. We found that the mutant phenotype is exacerbated in a dose-dependent fashion by high dietary sugar levels. tko25t larvae were found to exhibit severe metabolic abnormalities that were further accentuated by high-sugar diet. These include elevated pyruvate and lactate, decreased ATP and NADPH. Dietary pyruvate or lactate supplementation phenocopied the effects of high sugar. Based on tissue-specific rescue, the crucial tissue in which this metabolic crisis initiates is the gut. It is accompanied by down-regulation of the apparatus of cytosolic protein synthesis and secretion at both the RNA and post-translational levels, including a novel regulation of S6 kinase at the protein level. PMID- 26812174 TI - Bordetella pertussis Strain Lacking Pertactin and Pertussis Toxin. AB - A Bordetella pertussis strain lacking 2 acellular vaccine immunogens, pertussis toxin and pertactin, was isolated from an unvaccinated infant in New York State in 2013. Comparison with a French strain that was pertussis toxin-deficient, pertactin wild-type showed that the strains carry the same 28-kb deletion in similar genomes. PMID- 26812175 TI - Laser-driven phase transitions in aqueous colloidal gold nanoparticles under high pressure: picosecond pump-probe study. AB - Pump-probe transient extinction spectroscopy was used to analyze 355 nm picosecond laser heating-induced phenomena in 60 nm-diameter aqueous gold nanoparticles (AuNPs) under a high pressure of 60 MPa. Kinetic spectroscopy revealed that a supercritical layer surrounding the AuNP nucleated with a lifetime of approximately 1 ns during its dynamic expansion and decay for a fluence of 19.6 mJ cm(-2). Moreover, in the post-mortem transmission electron micrographs we observed a number of fragments, a small percentage of size-reduced cores, and erupted particles among the intact particles after 60 shots, suggesting that evaporation occurred under laser illumination. The particle temperature calculation indicated that evaporation begins with a liquid droplet AuNP surrounded by a supercritical layer at temperatures below the boiling point of gold. By applying high pressure, we obtained a clear picture of the evaporation event, which was not possible at ambient pressure because bubble formation caused particle temperatures to rise uncontrollably. In this study, we shed light on the critical role of the supercritical layer formed around the AuNP under high pressure during laser-induced evaporation. PMID- 26812176 TI - Quantification of naphthoquinone mercapturic acids in urine as biomarkers of naphthalene exposure. AB - Naphthalene shows carcinogenic properties in animal experiments. As the substance is ubiquitary present in the environment and has a possibly high exposure at industrial workplaces, the determination of naphthalene metabolites in humans is of environmental-medical as well as occupational-medical importance. Here, biomarkers of 1,2- and 1,4-naphthoquinone, as possibly carcinogenic metabolites in the naphthalene metabolism, are of outstanding significance. We developed and validated a liquid chromatography-tandem mass-spectrometric (LC-MS/MS) method for the simultaneous determination of the naphthoquinone mercapturic acids of 1,2- and 1,4-naphthoquinone in human urine samples as a sum of naphthoquinone- and dihydroxynaphthalene-mercapturic acid. Except for enzymatic hydrolysis and acidification, no further sample preparation is necessary. For sample clean-up, a column switching procedure is applied. The mercapturic acids are extracted from the urinary matrix on a restricted access material (RAM RP 18) and separated on a reversed phase column (Synergi Polar RP C18). The metabolites were quantified by tandem mass spectrometry using labelled D5-1,4-NQMA as internal standard. The limits of detection are 3MUg/l for 1,2-NQMA and 1MUg/l for 1,4-NQMA. Intraday- and interday precision for pooled urine (spiked with 10MUg/l and 30MUg/l of the analytes) ranges from 5.9 to 15.1% for 1,2-NQMA and from 2.0 to 10.8% for 1,4 NQMA. The developed method is suited for the sensitive and specific determination of the mercapturic acids of naphthoquinones in human urine. A good precision and low limits of detection were achieved. Application of those new biomarkers in biomonitoring studies may give deeper insights into the mechanisms of the human naphthalene metabolism. PMID- 26812177 TI - An optimized method for neurotransmitters and their metabolites analysis in mouse hypothalamus by high performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry. AB - Neurotransmitters (NTs) and their metabolites are known to play an essential role in maintaining various physiological functions in nervous system. However, there are many difficulties in the detection of NTs together with their metabolites in biological samples. A new method for NTs and their metabolites detection by high performance liquid chromatography coupled with Q Exactive hybrid quadruple orbitrap high-resolution accurate mass spectrometry (HPLC-HRMS) was established in this paper. This method was a great development of the applying of Q Exactive MS in the quantitative analysis. This method enabled a rapid quantification of ten compounds within 18min. Good linearity was obtained with a correlation coefficient above 0.99. The concentration range of the limit of detection (LOD) and the limit of quantitation (LOQ) level were 0.0008-0.05nmol/mL and 0.002 25.0nmol/mL respectively. Precisions (relative standard deviation, RSD) of this method were at 0.36-12.70%. Recovery ranges were between 81.83% and 118.04%. Concentrations of these compounds in mouse hypothalamus were detected by Q Exactive LC-MS technology with this method. PMID- 26812178 TI - sHLA-G1 and HLA-G5 levels are decreased in Tunisian women with multiple abortion. AB - Pregnancy is associated with increased levels of soluble (s) human leukocyte antigen (HLA)-G molecules, while during abortion these molecules are decreased. To date, little is known about the role of sHLA-G isoforms during abortion. In this study, we investigated the levels of total sHLA-G and its isoforms: HLA-G1 (membrane shedded isoform) and alternative spliced HLA-G5 in plasma samples obtained from 55 women who had experienced spontaneous abortion, 108 pregnant healthy women and 56 non pregnant healthy women. We found that pregnant women exhibited higher amounts of sHLA-G compared to either non pregnant women or women with abortion. Among women who had experienced spontaneous abortion, women with recurrent abortions (RSA) had lower sHLA-G than women with only one abortion. In particular, RSA women were characterized by the absence of sHLA-G1 isoform, suggesting a possible implication in abortion event. PMID- 26812179 TI - Rotational Study of Dimethyl Ether-Chlorotrifluoroethylene: Lone Pair...pi Interaction Links the Two Subunits. AB - The rotational spectra of two isotopologues of chlorotrifluoroethylene-dimethyl ether show that the two constituent molecules are held together by a lone pair...pi interaction. The ether oxygen is linked to the (CF2) carbon atom, with a C-O distance of 2.908 A. PMID- 26812181 TI - Switching on mTORC1 induces neurogenesis but not proliferation in neural stem cells of young mice. AB - Recent evidence reported that activation of the mechanistic target of rapamycin complex 1 (mTORC1) induces terminal differentiation of neural stem cells (NSCs) in the neonatal subventricular zone (SVZ), but did not affect their proliferation. Here, we investigated whether such an effect of hyperactive mTORC1 would be recapitulated in young adults following removal of the negative mTORC1 regulator TSC1as seen in the neurological disorder tuberous sclerosis complex, TSC. Conditional mTORC1 activation in NSCs of 3-4 weeks old mice resulted in the generation of proliferative (Ki67+) cells and newborn neuroblasts. However, hyperactive mTORC1 did not induce NSCs to proliferate, consistent with the findings that mTORC1 induces symmetric division and differentiation of slow cycling NSCs into proliferative daughter cells. Taken together these data suggest that hyperactivity of mTORC1 could lead to the progressive loss of NSCs over time. PMID- 26812182 TI - Residual Limb Hyperhidrosis and RimabotulinumtoxinB: A Randomized Placebo Controlled Study. AB - OBJECTIVE: To investigate the use of rimabotulinumtoxinB (BoNT/B [Myobloc]) compared with placebo in treating hyperhidrosis in the residual limbs of individuals with amputation. DESIGN: Randomized, double-blind, placebo-controlled pilot study. SETTING: Military medical center. PARTICIPANTS: Male participants (N=9) with 11 major amputations of the lower limbs and who complained of excessive sweating in their residual limbs were enrolled in the study between September 24, 2008 to October 28, 2011. Participants' lower limbs were randomly assigned to receive injections of either BoNT/B (n=7) or placebo (n=4). INTERVENTION: BoNT/B. MAIN OUTCOME MEASURES: The primary efficacy variable was a minimum of 50% reduction in sweat production 4 weeks after the injection as measured via gravimetric sweat analysis after 10 minutes of physical exertion. Secondary analyses were performed on prosthetic function and pain. RESULTS: All volunteers (100%; 7) in the BoNT/B group achieved a minimum of 50% reduction in sweat production as compared with only 50% (2) in the placebo group. The percent reduction was significantly greater for the BoNT/B group than for the placebo group (-72.7%+/-15.7% vs -32.7%+/-39.2%; P<.05). Although both groups subjectively self-reported significant sweat reduction and improved prosthetic function (P<.05 for both), objective gravimetric sweat analyses significantly decreased only for the BoNT/B group (2.3+/-2.3g vs 0.7+/-1.1g; P<.05). Neither group reported a change in phantom limb pain or residual limb pain (P>.05 for both). CONCLUSIONS: BoNT/B successfully reduces sweat production in individuals with residual limb hyperhidrosis, but does not affect pain. No differences were found in perceived effect on prosthetic use between BoNT/B and placebo groups. PMID- 26812180 TI - One Dose of Staphylococcus aureus 4C-Staph Vaccine Formulated with a Novel TLR7 Dependent Adjuvant Rapidly Protects Mice through Antibodies, Effector CD4+ T Cells, and IL-17A. AB - A rapidly acting, single dose vaccine against Staphylococcus aureus would be highly beneficial for patients scheduled for major surgeries or in intensive care units. Here we show that one immunization with a multicomponent S. aureus candidate vaccine, 4C-Staph, formulated with a novel TLR7-dependent adjuvant, T7 alum, readily protected mice from death and from bacterial dissemination, both in kidney abscess and peritonitis models, outperforming alum-formulated vaccine. This increased efficacy was paralleled by higher vaccine-specific and alpha hemolysin-neutralizing antibody titers and Th1/Th17 cell responses. Antibodies played a crucial protective role, as shown by the lack of protection of 4C Staph/T7-alum vaccine in B-cell-deficient mice and by serum transfer experiments. Depletion of effector CD4+ T cells not only reduced survival but also increased S. aureus load in kidneys of mice immunized with 4C-Staph/T7-alum. The role of IL 17A in the control of bacterial dissemination in 4C-Staph/T7-alum vaccinated mice was indicated by in vivo neutralization experiments. We conclude that single dose 4C-Staph/T7-alum vaccine promptly and efficiently protected mice against S. aureus through the combined actions of antibodies, CD4+ effector T cells, and IL 17A. These data suggest that inclusion of an adjuvant that induces not only fast antibody responses but also IL-17-producing cell-mediated effector responses could efficaciously protect patients scheduled for major surgeries or in intensive care units. PMID- 26812183 TI - A High Performance Platform Based on cDNA Display for Efficient Synthesis of Protein Fusions and Accelerated Directed Evolution. AB - We describe a high performance platform based on cDNA display technology by developing a new modified puromycin linker-oligonucleotide. The linker consists of four major characteristics: a "ligation site" for hybridization and ligation of mRNA by T4 RNA ligase, a "puromycin arm" for covalent linkage of the protein, a "polyadenosine site" for a longer puromycin arm and purification of protein fusions (optional) using oligo-dT matrices, and a "reverse transcription site" for the formation of stable cDNA protein fusions whose cDNA is covalently linked to its encoded protein. The linker was synthesized by a novel branching strategy and provided >8-fold higher yield than previous linkers. This linker enables rapid and highly efficient ligation of mRNA (>90%) and synthesis of protein fusions (~ 50-95%) in various cell-free expression systems. Overall, this new cDNA display method provides 10-200 fold higher end-usage fusions than previous methods and benefits higher diversity libraries crucial for directed protein/peptide evolution. With the increased efficiency, this system was able to reduce the time for one selection cycle to <8 h and is potentially amenable to high-throughput systems. We demonstrate the efficiency of this system for higher throughput selections of various biomolecular interactions and achieved 30-40 fold enrichment per selection cycle. Furthermore, a 4-fold higher enrichment of Flag-tag was obtained from a doped mixture compared with that of the previous cDNA display method. A three-finger protein library was evolved to isolate superior nanomolar range binding candidates for vascular endothelial growth factor. This method is expected to provide a beneficial impact to accelerated drug discovery and proteome analysis. PMID- 26812184 TI - Capillary Trapping of CO2 in Oil Reservoirs: Observations in a Mixed-Wet Carbonate Rock. AB - Early deployment of carbon dioxide storage is likely to focus on injection into mature oil reservoirs, most of which occur in carbonate rock units. Observations and modeling have shown how capillary trapping leads to the immobilization of CO2 in saline aquifers, enhancing the security and capacity of storage. There are, however, no observations of trapping in rocks with a mixed-wet-state characteristic of hydrocarbon-bearing carbonate reservoirs. Here, we found that residual trapping of supercritical CO2 in a limestone altered to a mixed-wet state with oil was significantly less than trapping in the unaltered rock. In unaltered samples, the trapping of CO2 and N2 were indistinguishable, with a maximum residual saturation of 24%. After the alteration of the wetting state, the trapping of N2 was reduced, with a maximum residual saturation of 19%. The trapping of CO2 was reduced even further, with a maximum residual saturation of 15%. Best-fit Land-model constants shifted from C = 1.73 in the water-wet rock to C = 2.82 for N2 and C = 4.11 for the CO2 in the mixed-wet rock. The results indicate that plume migration will be less constrained by capillary trapping for CO2 storage projects using oil fields compared with those for saline aquifers. PMID- 26812187 TI - The AYA Cancer Patient's Survivorship: Challenges and Opportunities. PMID- 26812186 TI - Meta-analysis comparing the efficacy of anti-EGFR monoclonal antibody therapy between KRAS G13D and other KRAS mutant metastatic colorectal cancer tumours. AB - BACKGROUND: Metastatic colorectal cancer (mCRC) tumours harbouring a RAS mutation are associated with a lack of treatment benefit from anti-EGFR monoclonal antibodies (mAbs). However, observational evidence has led to speculation that mCRC patients with KRAS G13D mutant (MT) tumours may derive a benefit from treatment with anti-EGFR mAbs. METHODS: We conducted a systematic review and meta analysis of randomized controlled trials (RCTs) to evaluate whether the efficacy of anti-EGFR mAbs for mCRC differs between tumours harbouring a KRAS G13D mutation (KRAS G13D) and KRAS mutations other than G13D (other KRAS MT). RESULTS: Eight RCTs (n = 5967) met the inclusion criteria for assessment of both overall survival (OS) and progression-free survival (PFS). For other KRAS MT the hazard ratio for OS benefit with addition of anti-EGFR mAb therapy was 1.06 (95% confidence interval [CI]; 0.96, 1.17), compared to 1.08 (95% CI; 0.73, 1.60) for KRAS G13D [test for interaction p=0.99]. In contrast, the hazard ratio for KRAS wild-type (WT) tumours was 0.85 (95% CI; 0.76, 0.95). Regarding PFS benefit with anti-EGFR mAbs, the hazard ratio was 1.07 (95% CI; 0.92, 1.26) for other KRAS MT, 0.96 (95% CI; 0.73, 1.27) for KRAS G13D, and 0.68 (95% CI; 0.54, 0.85) for KRAS WT. Again, the test for interaction (p=0.46) demonstrated no significant difference in PFS benefit for anti-EGFR mAb therapy between KRAS G13D and other KRAS MT. CONCLUSION: This meta-analysis demonstrates no significant difference between KRAS G13D and other KRAS MT tumours in terms of treatment benefit from anti-EGFR mAbs for mCRC. PMID- 26812188 TI - Barriers and Facilitators of Transition from Pediatric to Adult Long-Term Follow Up Care in Childhood Cancer Survivors. AB - PURPOSE: Despite the risk for late effects in adult survivors of cancer in childhood or adolescence, many survivors fail to transition from pediatric to adult long-term follow-up (LTFU) care. The purpose of this study was to identify the barriers and facilitators of transition from pediatric to adult LTFU care. METHODS: In this qualitative study, 38 Canadian survivors of cancer in childhood or adolescence, currently aged 15-26 years, were interviewed using semi structured, open-ended questions. Participants belonged to one of four groups: pre-transition (n=10), successful transition (n=11), failed to transition (n=7), and transitioned to an adult center but then dropped out of adult care (n=10). A constructivist grounded theory approach was used to analyze the interview data. This approach consisted of coding transcripts line by line to develop categories and using constant comparison to examine relationships within and across codes and categories. Interviewing continued until saturation was reached. RESULTS: Three interrelated themes were identified that affected the transition process: micro-level patient factors (e.g., due diligence, anxiety), meso-level support factors (e.g., family, friends), and macro-level system factors (e.g., appointments, communication, healthcare providers). Factors could act as facilitators to transition (e.g., family support), barriers to transition (e.g., difficulty booking appointments), or as both a barrier and a facilitator (e.g., anxiety). CONCLUSION: This study illustrates the interaction between multiple factors that facilitate and/or prevent transition from pediatric to adult LTFU cancer care. A number of recommendations are presented to address potential macro level system barriers to successful transition. PMID- 26812189 TI - The Challenge of Access to Care for Adolescents with Cancer in Italy: National and Local Pediatric Oncology Programs. International Perspectives on AYAO, Part 2. AB - This paper, summarizing the March 2012 presentation at the second international workshop of the Canadian Task Force on Adolescents and Young Adults with Cancer, describes the situation in Italy concerning the inadequate access to optimal cancer services for adolescents, and the need to improve the quality of care for these patients while investing in more research on the diseases that afflict them. National actions to bridge the gap in care and implement specific programs tailored to these patients arose from the pediatric oncology community. These actions include creation of the national Committee on Adolescents of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP), founded with the mission of ensuring that Italian adolescents with cancer have prompt, adequate, and equitable access to the best care to optimize their treatment outcome and quality of life. Also developed was the Youth Project of the pediatric oncology unit at the Istituto Nazionale Tumori in Milan, which is currently dedicated to adolescents aged 15-19 years old and may eventually serve young adults up to the age of 25 that are affected by pediatric-type tumors. PMID- 26812190 TI - Youth Cancer Services in Australia: Development and Implementation. International Perspectives on AYAO, Part 3. AB - Based on an increased appreciation of the unique challenges facing adolescents and young adults with cancer, there has been a coordinated national effort in Australia in recent years to address this issue. In 2007, CanTeen, a consumer support organization for young people with cancer, partnered with the Australian federal government to fund the development of a network of multidisciplinary Youth Cancer Services across the country. This has resulted in a collaborative effort involving clinicians, the federal and state governments, consumers, CanTeen, and other non-government organizations to implement equitable and sustainable models of care that will improve the coordination of services, treatment, and support for 15-25-year-olds with cancer. The aims of this article are to outline the origins of Youth Cancer Services in Australia, to discuss several innovative models of care that have developed according to local geographic and demographic need, to highlight some successful strategies and early obstacles to service development, and to outline the challenges for the future. PMID- 26812191 TI - Pregnancy During Recovery from Hematopoietic Stem Cell Transplant for Mycosis Fungoides. AB - We report a case of spontaneous pregnancy with subsequent full-term live birth following hematopoietic stem cell transplantation (HSCT) for mycosis fungoides in a 24-year-old nulligravida with 4 years of prior infertility due to primary ovarian insufficiency. Four months post-transplant, the patient was found to be 10 weeks pregnant. Her pregnancy was complicated by first trimester fetal exposure to mycophenolate mofetil (pregnancy category D), delayed-onset acute gastrointestinal graft-versus-host disease, and multiple systemic infections. This report highlights the importance of discussing potential fertility outcomes in patients undergoing HSCT, including the necessity for adequate contraception post-transplant, even in the setting of previous infertility. PMID- 26812192 TI - Impact of Serum Cytokine Levels on EEG-Measured Arousal Regulation in Patients with Major Depressive Disorder and Healthy Controls. AB - BACKGROUND: In major depressive disorder (MDD), findings include hyperstable regulation of brain arousal measured by electroencephalography (EEG) vigilance analysis and alterations in serum levels of cytokines. It is also known that cytokines affect sleep-wake regulation. This study investigated the relationship between cytokines and EEG vigilance in participants with MDD and nondepressed controls, and the influence of cytokines on differences in vigilance between the two groups. METHODS: In 60 patients with MDD and 129 controls, 15-min resting state EEG recordings were performed and vigilance was automatically assessed with the VIGALL 2.0 (Vigilance Algorithm Leipzig). Serum levels of the wakefulness promoting cytokines interleukin (IL)-4, IL-10, IL-13 and somnogenic cytokines tumor necrosis factor-alpha, interferon-x03B3; and IL-2 were measured prior to the EEG. RESULTS: Summed wakefulness-promoting cytokines, but not somnogenic cytokines, were significantly associated with the time course of EEG vigilance in the MDD group only. In both groups, IL-13 was significantly associated with the course of EEG vigilance. In MDD compared to controls, a hyperstable EEG vigilance regulation was found, significant for group and group * time course interaction. After controlling for wakefulness-promoting cytokines, differences in vigilance regulation between groups remained significant. CONCLUSIONS: The present study demonstrated a relationship between wakefulness-promoting cytokines and objectively measured EEG vigilance as an indicator for brain arousal. Altered brain arousal regulation in MDD gives support for future evaluation of vigilance measures as a biomarker in MDD. Since interactions between cytokines and EEG vigilance only moderately differed between the groups and cytokine levels could not explain the group differences in EEG vigilance regulation, cytokines and brain arousal regulation are likely to be associated with MDD in independent ways. PMID- 26812185 TI - The Halogen Bond. AB - The halogen bond occurs when there is evidence of a net attractive interaction between an electrophilic region associated with a halogen atom in a molecular entity and a nucleophilic region in another, or the same, molecular entity. In this fairly extensive review, after a brief history of the interaction, we will provide the reader with a snapshot of where the research on the halogen bond is now, and, perhaps, where it is going. The specific advantages brought up by a design based on the use of the halogen bond will be demonstrated in quite different fields spanning from material sciences to biomolecular recognition and drug design. PMID- 26812194 TI - Lateral Violence in Nursing and the Theory of the Nurse as Wounded Healer. AB - Lateral violence (LV), a deliberate and harmful behavior demonstrated in the workplace by one employee to another, is a significant problem in the nursing profession. The many harmful effects of LV negatively impact both the work environment and the nurse's ability to deliver optimal patient care. In this article, the authors explain how Conti-O'Hare's Theory of the Nurse as Wounded Healer can be used in situations of lateral violence to resolve personal and/or professional pain, build therapeutic relationships, and promote positive work environments. A working model of the theory is applied to the experience of LV in nursing to demonstrate the nurse's path from being the 'walking wounded' to becoming a 'wounded healer.' Implications of this theory for promoting the process of healing and creating an environment that disenables violence are presented; an example is provided. The authors conclude that both practitioners and managers must be aware of the occurrence of LV and of the need for healing. They note that the 'journey of the walking wounded' is an ideal pathway to bring about this healing. As nurses promote health in their patients, they must also promote health in themselves and one another. PMID- 26812195 TI - Ethics: The Challenge of Ethical, Legal, and Social Implications (ELSI) in Genomic Nursing. PMID- 26812196 TI - Informatics: The Standardized Nursing Terminologies: A National Survey of Nurses' Experience and Attitudes--SURVEY II: Participants' Documentation Use of Standardized Nursing Terminologies. PMID- 26812197 TI - Legislative: Interprofessional Collaboration: What's Taking So Long? PMID- 26812198 TI - Healthy People 2020 Objectives for Violence Prevention and the Role of Nursing. AB - Violence, including child maltreatment, youth violence, intimate partner violence, and sexual violence, is a significant public health problem in the United States. A public health approach can help providers understand the health burden from violence, evaluate evidence for prevention strategies, and learn where to turn for information about planning and implementing prevention strategies for this preventable problem. For the past three decades, the U.S. Department of Health and Human Services has published "Healthy People" objectives for the next decade. The Healthy People 2020 initiative includes 13 measurable objectives related to violence prevention, one of which was selected as a Healthy People 2020 Leading Health Indicator. Progress to achieve these objectives can save thousands of lives, reduce the suffering of victims and their families, and decrease financial cost to the law enforcement and healthcare systems. The role that nurses can and do play in violence prevention is critical and extends beyond just caring for victims to also include preventing violence before it happens. This article summarizes the violence prevention objectives in Healthy People 2020 and the resources for prevention available to support nurses and others as they move prevention efforts forward in communities to stop violence before it starts. PMID- 26812193 TI - Inflammatory and oxidative stress-related effects associated with neurotoxicity are maintained after exclusively prenatal trichloroethylene exposure. AB - Trichloroethylene (TCE) is a widespread environmental toxicant with immunotoxic and neurotoxic potential. Previous studies have shown that continuous developmental exposure to TCE encompassing gestation and early life as well as postnatal only exposure in the drinking water of MRL+/+ mice promoted CD4+ T cell immunotoxicity, glutathione depletion and oxidative stress in the cerebellum, as well increased locomotor activity in male offspring. The purpose of this study was to characterize the effects of exclusively prenatal exposure on these parameters. Another goal was to investigate potential plasma oxidative stress/inflammatory biomarkers to possibly be used as predictors of TCE-mediated neurotoxicity. In the current study, 6 week old male offspring of dams exposed gestationally to 0, 0.01, and 0.1mg/ml TCE in the drinking water were evaluated. Our results confirmed that the oxidized phenotype in plasma and cerebellum was maintained after exclusively prenatal exposure. A Phenotypic analysis by flow cytometry revealed that TCE exposure expanded the effector/memory subset of peripheral CD4+ T cells in association with increased production of pro inflammatory cytokines IFN-gamma and IL-17. Serum biomarkers of oxidative stress and inflammation were also elevated in plasma suggesting that systemic effects are important and may be used to predict neurotoxicity in our model. These results suggested that the prenatal period is a critical stage of life by which the developing CNS and immune system are susceptible to long-lasting changes mediated by TCE. PMID- 26812199 TI - Child Maltreatment: A Public Health Overview and Prevention Considerations. AB - Child maltreatment (CM) is a significant public health problem, affecting hundreds of millions of children globally. CM has been linked to a variety of short- and long-term health consequences, including poor physical and mental health, changes to brain architecture and development, altered biological factors, reduced cognitive ability and educational achievement, and impaired psychosocial functioning. This article will define and describe the various types of CM and its epidemiology from a public health perspective that considers incidence, prevalence, and consequences. The authors discuss risk and protective factors and approaches for the prevention of CM, including key considerations for nurses to help identify potential victims and provide treatment and/or referrals. PMID- 26812200 TI - Supporting Gang Violence Prevention Efforts: A Public Health Approach for Nurses. AB - The impact of gang violence on a youth's risk for death or injury is tremendous. Prevention of complex societal problems, such as gang violence, requires a substantial effort and commitment from many sectors and disciplines. Nurses are uniquely positioned to help lead such efforts. Understanding the public health perspective to gang violence may be an important tool for nurses attempting to prevent this problem. The public health approach has four key components: defining and monitoring the problem; identifying risk, protective, and promoting factors; developing and evaluating interventions; and dissemination. This article outlines these components, current research on gang violence, and concludes by summarizing critical challenges for nurses to consider as they contribute to public health initiatives to prevent gang violence. PMID- 26812202 TI - Metallic Borides, La2Re3B7 and La3Re2B5, Featuring Extensive Boron-Boron Bonding. AB - La2Re3B7 and La3Re2B5 have been synthesized in single-crystalline form from a molten La/Ni eutectic at 1000 degrees C in the first example of the flux crystal growth of ternary rare-earth rhenium borides. Both compounds crystallize in their own orthorhombic structure types, with La2Re3B7 (space group Pcca) having lattice parameters a = 7.657(2) A, b = 6.755(1) A, and c = 11.617(2) A, and La3Re2B5 (space group Pmma) having lattice parameters a = 10.809(2) A, b = 5.287(1) A, and c = 5.747(1) A. The compounds possess three-dimensional framework structures that are built up from rhenium boride polyhedra and boron-boron bonding. La3Re2B5 features fairly common B2 dumbbells, whereas La2Re3B7 has unique one-dimensional subunits composed of alternating triangular B3 and trans-B4 zigzag chain fragments. Also observed in La3Re2B5 is an unusual coordination of B by an octahedron of La atoms. Electronic band structure calculations predict that La2Re3B7 is a semimetal, which is observed in the electrical resistivity data as measured on single crystals, with behavior obeying the Bloch-Gruneisen model and a room-temperature resistivity rho300 K of ~375 MUOmega cm. The electronic band structure calculations also suggest that La3Re2B5 is a regular metal. PMID- 26812201 TI - Violence in the School Setting: A School Nurse Perspective. AB - Violence in schools has become a significant public health risk and is not limited to violent acts committed in the school setting. Violence in homes, neighborhoods, and communities also affects the learning and behaviors of children while at school. School violence, such as shootings, weapons in schools, assaults, fights, bullying; other witnessed violence in non-school settings; and violence as a cultural norm of problem solving can all impact the ability of children to function in school. School nurses serve on the front-line of problem identification and intervene to diminish the effects of violence on both school children as individuals and on populations in schools and the community. This article describes ways in which school nurses deal with violence and concludes with discussion of potential responses to violence, including the school nurse response to violence and implications for other healthcare professionals. PMID- 26812203 TI - Initial Costs of Ebola Treatment Centers in the United States. PMID- 26812204 TI - Design and optimization of disintegrating pellets of MCC by non-aqueous extrusion process using statistical tools. AB - The objective of the study was to design and optimize a disintegrating pellet formulation of microcrystalline cellulose by non-aqueous extrusion process for a water sensitive drug using various statistical tools. Aspirin was used as a model drug. Disintegrating matrix pellets of aspirin using propylene glycol as a non aqueous granulation liquid and croscarmellose as a disintegrant was developed. Plackett-Burman design was initially conducted to screen and identify the significant factors. Final optimization of formula was performed by response surface methodology using a central composite design. The critical attributes of the pellet dosage forms (dependent variables); disintegration time, sphericity and yield were predicted with adequate accuracy based on the regression model. Pareto charts and contour charts were studied to understand the influence of factors and predict the responses. A design space was constructed to meet the desirable targets of the responses in terms of disintegration time <5min, maximum yield, sphericity >0.95 and friability <1.7%. The optimized matrix pellets were enteric coated using Eudragit L 100. The drug release from the enteric coated pellets after 30min in the basic media was ~93% when compared to ~77% from the marketed pellets. The delayed release pellets stored at 25 degrees C/60% RH were stable for a period of 10mo. In conclusion, it can be stated that the developed process for disintegrating pellets using non-aqueous granulating agents can be used as an alternative technique for various water sensitive drugs, circumventing the application of volatile organic solvents in conventional drug layering on inert cores. The scope of this study can be further extended to hydrophobic drugs, which may benefit from the rapid disintegration property and the use of various hydrophilic excipients used in the optimized pellet formulation to enhance dissolution and in turn improve bioavailability. PMID- 26812205 TI - Hyperbaric Oxygen Alleviates Secondary Brain Injury After Trauma Through Inhibition of TLR4/NF-kappaB Signaling Pathway. AB - BACKGROUND: The aim of this study was to investigate the efficacy of hyperbaric oxygen in secondary brain injury after trauma and its mechanism in a rat model. MATERIAL/METHODS: A rat model of TBI was constructed using the modified Feeney's free-fall method, and 60 SD rats were randomly divided into three groups--the sham group, the untreated traumatic brain injury (TBI) group, and the hyperbaric oxygen-treated TBI group. The neurological function of the rats was evaluated 12 and 24 hours after TBI modeling; the expression levels of TLR4, IkappaB, p65, and cleaved caspase-3 in the peri-trauma cortex were determined by Western blot; levels of TNF-alpha, IL-6, and IL-1beta were determined by ELISA; and apoptosis of the neurons was evaluated by TUNEL assay 24 hours after TBI modeling. RESULTS: Hyperbaric oxygen therapy significantly inhibited the activation of the TLR4/NF kappaB signaling pathway, reduced the expression of cleaved caspase-3, TNF-alpha, IL-6 and IL-1beta (P<0.05), reduced apoptosis of the neurons and improved the neurological function of the rats (P<0.05). CONCLUSIONS: Hyperbaric oxygen therapy protects the neurons after traumatic injury, possibly through inhibition of the TLR4/NF-kappaB signaling pathway. PMID- 26812206 TI - The effect of maternal immunization on female oxidative status, yolk antioxidants and offspring survival in a songbird. AB - Immune defense involves inflammatory reactions in which immune cells produce reactive oxygen species (ROS) to fight pathogens. ROS may however cause damage to the host if they are not balanced by antioxidant defenses. Therefore, one should expect individuals undergoing an immune reaction to use antioxidants to prevent oxidative stress. Antioxidants are vital compounds that provide important protection against oxidative damage of embryos and newly hatched chicks. Thus, during egg laying a female that contracted an infection may face a trade-off between the allocation of antioxidants into self-maintenance and into her offspring via the eggs. In our study we investigated whether immunized females face this trade-off and consequently modify the antioxidant allocation into the eggs and whether this allocation affects offspring performance. We injected female zebra finches (Taeniopygia guttata) with lipopolysaccharide prior to egg laying while some females were left unimmunized. We removed the second egg of each clutch, while we allowed the other eggs to hatch. We assessed oxidative stress in females 24h after immunization, yolk antioxidant capacity of the second egg of the clutch and survival success of the offspring until adulthood. Compared to controls, immunized females had higher oxidative damage, but similar plasma non-enzymatic antioxidant levels. The treatment did not affect yolk antioxidants, clutch size, laying date and offspring survival. However, we found a positive correlation between yolk antioxidant capacity and offspring survival, irrespective of the treatment. Our study suggests that our immune challenge may not have changed female strategy of antioxidant allocation between self maintenance and offspring survival. PMID- 26812207 TI - Structural and Calorimetric Studies Demonstrate that Xeroderma Pigmentosum Type G (XPG) Can Be Imported to the Nucleus by a Classical Nuclear Import Pathway via a Monopartite NLS Sequence. AB - Xeroderma pigmentosum type G (XPG) proteins are involved in DNA lesion recognition and promotion of nucleotide excision repair. Specific mutations in these proteins may lead to Cockayne syndrome, in which the patients may display severe developmental retardation and neurological abnormalities. No structural information is available for their spacer region or the C-terminal domain, which are important, respectively, for specific nucleotide excision repair activity and substrate specificity, as well as nuclear translocation. Immunofluorescence studies suggested two specific regions of the XPG C-terminus as potential bipartite nuclear localization sequences, which would be responsible for its translocation to the nucleus by the classical nuclear import pathway mediated by the importin-alpha (Impalpha). Thus, in order to test these hypotheses and gain insight into the structural basis for the nuclear import process for the XPG protein, we solved the crystal structures of complexes formed by the Impalpha and peptides corresponding to both putative nuclear localization signal (NLS) sequences (XPG1 and XPG2) and performed isothermal titration calorimetry assays to determine their binding affinities. Structural experiments confirm the binding of both NLS peptides to Impalpha but, unexpectedly, they bind to the receptor as monopartite NLSs. The isothermal titration calorimetry assays demonstrated that XPG1 and XPG2 peptides bind to two separate binding sites, but with high affinity to the major NLS-binding site of the Impalpha, resembling classical monopartite SV40 TAg NLS. The results lead to insights about what distinguishes monopartite and bipartite NLSs, as well as the differential roles of XPG1 and XPG2 NLSs in the nuclear localization of XPG. PMID- 26812208 TI - Generation of Fluorogen-Activating Designed Ankyrin Repeat Proteins (FADAs) as Versatile Sensor Tools. AB - Fluorescent probes constitute a valuable toolbox to address a variety of biological questions and they have become irreplaceable for imaging methods. Commonly, such probes consist of fluorescent proteins or small organic fluorophores coupled to biological molecules of interest. Recently, a novel class of fluorescence-based probes, fluorogen-activating proteins (FAPs), has been reported. These binding proteins are based on antibody single-chain variable fragments and activate fluorogenic dyes, which only become fluorescent upon activation and do not fluoresce when free in solution. Here we present a novel class of fluorogen activators, termed FADAs, based on the very robust designed ankyrin repeat protein scaffold, which also readily folds in the reducing environment of the cytoplasm. The FADA generated in this study was obtained by combined selections with ribosome display and yeast surface display. It enhances the fluorescence of malachite green (MG) dyes by a factor of more than 11,000 and thus activates MG to a similar extent as FAPs based on single-chain variable fragments. As shown by structure determination and in vitro measurements, this FADA was evolved to form a homodimer for the activation of MG dyes. Exploiting the favorable properties of the designed ankyrin repeat protein scaffold, we created a FADA biosensor suitable for imaging of proteins on the cell surface, as well as in the cytosol. Moreover, based on the requirement of dimerization for strong fluorogen activation, a prototype FADA biosensor for in situ detection of a target protein and protein-protein interactions was developed. Therefore, FADAs are versatile fluorescent probes that are easily produced and suitable for diverse applications and thus extend the FAP technology. PMID- 26812209 TI - Overexpression of the Replicative Helicase in Escherichia coli Inhibits Replication Initiation and Replication Fork Reloading. AB - Replicative helicases play central roles in chromosome duplication and their assembly onto DNA is regulated via initiators and helicase loader proteins. The Escherichia coli replicative helicase DnaB and the helicase loader DnaC form a DnaB6-DnaC6 complex that is required for loading DnaB onto single-stranded DNA. Overexpression of dnaC inhibits replication by promoting continual rebinding of DnaC to DnaB and consequent prevention of helicase translocation. Here we show that overexpression of dnaB also inhibits growth and chromosome duplication. This inhibition is countered by co-overexpression of wild-type DnaC but not of a DnaC mutant that cannot interact with DnaB, indicating that a reduction in DnaB6-DnaC6 concentration is responsible for the phenotypes associated with elevated DnaB concentration. Partial defects in the oriC-specific initiator DnaA and in PriA specific initiation away from oriC during replication repair sensitise cells to dnaB overexpression. Absence of the accessory replicative helicase Rep, resulting in increased replication blockage and thus increased reinitiation away from oriC, also exacerbates DnaB-induced defects. These findings indicate that elevated levels of helicase perturb replication initiation not only at origins of replication but also during fork repair at other sites on the chromosome. Thus, imbalances in levels of the replicative helicase and helicase loader can inhibit replication both via inhibition of DnaB6-DnaC6 complex formation with excess DnaB, as shown here, and promotion of formation of DnaB6-DnaC6 complexes with excess DnaC [Allen GC, Jr., Kornberg A. Fine balance in the regulation of DnaB helicase by DnaC protein in replication in Escherichia coli. J. Biol. Chem. 1991;266:22096-22101; Skarstad K, Wold S. The speed of the Escherichia coli fork in vivo depends on the DnaB:DnaC ratio. Mol. Microbiol. 1995;17:825-831]. Thus, there are two mechanisms by which an imbalance in the replicative helicase and its associated loader protein can inhibit genome duplication. PMID- 26812211 TI - Correction: Facilitated carbon dioxide reduction using a Zn(II) complex. PMID- 26812212 TI - Enhanced Photovoltaic Performances of Dye-Sensitized Solar Cells by Co Sensitization of Benzothiadiazole and Squaraine-Based Dyes. AB - Dye-sensitized solar cells (DSSCs) based on a donor-acceptor-donor oligothienylene dye containing benzothiadiazole (T4BTD-A) were cosensitized with dyes containing cis-configured squaraine rings (HSQ3 and HSQ4). The cosensitized dyes showed incident monochromatic photon-to-current conversion efficiency (IPCE) greater than 70% in the 300-850 nm wavelength region. The individual overall conversion efficiencies of the sensitizers T4BTD-A, HSQ3, and HSQ4 were 6.4%, 4.8%, and 5.8%, respectively. Improved power conversion efficiencies of 7.0% and 7.7% were observed when T4BTD-A was cosensitized with HSQ3 and HSQ4, respectively, thanks to a significant increase in current density (JSC) for the cosensitized DSSCs. Intensity-modulated photovoltage spectroscopy results showed a longer lifetime for cosensitized T4BTD-A+HSQ3 and T4BTD-A+HSQ4 compared to that of HSQ3 and HSQ4, respectively. PMID- 26812210 TI - Monitoring Ligand-Induced Protein Ordering in Drug Discovery. AB - While the gene for p53 is mutated in many human cancers causing loss of function, many others maintain a wild-type gene but exhibit reduced p53 tumor suppressor activity through overexpression of the negative regulators, Mdm2 and/or MdmX. For the latter mechanism of loss of function, the activity of endogenous p53 can be restored through inhibition of Mdm2 or MdmX with small molecules. We previously reported a series of compounds based upon the Nutlin-3 chemical scaffold that bind to both MdmX and Mdm2 [Vara, B. A. et al. (2014) Organocatalytic, diastereo- and enantioselective synthesis of nonsymmetric cis-stilbene diamines: A platform for the preparation of single-enantiomer cis-imidazolines for protein-protein inhibition. J. Org. Chem. 79, 6913-6938]. Here we present the first solution structures based on data from NMR spectroscopy for MdmX in complex with four of these compounds and compare them with the MdmX:p53 complex. A p53-derived peptide binds with high affinity (Kd value of 150nM) and causes the formation of an extensive network of hydrogen bonds within MdmX; this constitutes the induction of order within MdmX through ligand binding. In contrast, the compounds bind more weakly (Kd values from 600nM to 12MUM) and induce an incomplete hydrogen bond network within MdmX. Despite relatively weak binding, the four compounds activated p53 and induced p21(Cip1) expression in retinoblastoma cell lines that overexpress MdmX, suggesting that they specifically target MdmX and/or Mdm2. Our results document structure-activity relationships for lead-like small molecules targeting MdmX and suggest a strategy for their further optimization in the future by using NMR spectroscopy to monitor small-molecule-induced protein order as manifested through hydrogen bond formation. PMID- 26812213 TI - MRI morphometry in Alzheimer's disease. AB - MRI based evaluation of brain atrophy is regarded as a valid method to stage the disease and to assess progression in Alzheimer's disease (AD). Volumetric software programs have made it possible to quantify gray matter in the human brain in an automated fashion. At present, voxel based morphometry (VBM) is easily applicable to the routine clinical procedure with a short execution time. The importance of the VBM approach is that it is not biased to one particular structure and is able to assess anatomical differences throughout the brain. Stand-alone VBM software running on Windows, Voxel-based Specific Regional analysis system for AD (VSRAD), has been widely used in the clinical diagnosis of AD in Japan. On the other hand, recent application of graph theory to MRI has made it possible to analyze changes in structural connectivity in AD. PMID- 26812214 TI - Epidemiology of Serotype 1 Invasive Pneumococcal Disease, South Africa, 2003 2013. AB - In South Africa, 7-valent pneumococcal conjugate vaccine (PCV) was introduced in April 2009 and replaced with 13-valent PCV in April 2011. We describe the epidemiology of serotype 1 Streptococcus pneumoniae disease during the pre- and post-PCV eras (2003-2013). Using laboratory-based invasive pneumococcal disease (IPD) surveillance, we calculated annual incidences, identified IPD clusters, and determined serotype 1-associated factors. Of 46,483 IPD cases, 4,544 (10%) were caused by serotype 1. Two clusters of serotype 1 infection were detected during 2003-2004 and 2008-2012, but incidence decreased after 2011. Among children <5 years of age, those who had non-serotype 1 IPD had shorter hospital stays, fewer cases of penicillin-nonsusceptible disease, and lower HIV prevalence and in hospital death rates than did those with serotype 1 IPD; similar factors were noted for older patients. Serotype 1 IPD had distinctive clinical features in South Africa, and annual incidences fluctuated, with decreases noted after the introduction of PCV13. PMID- 26812215 TI - Ag@Au Concave Cuboctahedra: A Unique Probe for Monitoring Au-Catalyzed Reduction and Oxidation Reactions by Surface-Enhanced Raman Spectroscopy. AB - We report a facile synthesis of Ag@Au concave cuboctahedra by titrating aqueous HAuCl4 into a suspension of Ag cuboctahedra in the presence of ascorbic acid (AA), NaOH, and poly(vinylpyrrolidone) (PVP) at room temperature. Initially, the Au atoms derived from the reduction of Au(3+) by AA are conformally deposited on the entire surface of a Ag cuboctahedron. Upon the formation of a complete Au shell, however, the subsequently formed Au atoms are preferentially deposited onto the Au{100} facets, resulting in the formation of a Ag@Au cuboctahedron with concave structures at the sites of {111} facets. The concave cuboctahedra embrace excellent SERS activity that is more than 70-fold stronger than that of the original Ag cuboctahedra at an excitation wavelength of 785 nm. The concave cuboctahedra also exhibit remarkable stability in the presence of an oxidant such as H2O2 because of the protection by a complete Au shell. These two unique attributes enable in situ SERS monitoring of the reduction of 4-nitrothiophenol (4-NTP) to 4-aminothiophenol (4-ATP) by NaBH4 through a 4,4'-dimercaptoazobenzene (trans-DMAB) intermediate and the subsequent oxidation of 4-ATP back to trans DMAB upon the introduction of H2O2. PMID- 26812216 TI - Novel Stratification of Mortality Risk by Kidney Disease Stage. AB - BACKGROUND: Chronic kidney disease (CKD) is a common disorder with a variable clinical course and it is associated with increased mortality. The Intermountain Risk Score (IMRS) is an electronic risk calculator that utilizes complete blood count (CBC) and basic metabolic panel (BMP) values to predict mortality in various healthcare populations. We hypothesized that IMRS would predict mortality in patients with CKD even with adjustment for serum phosphate and urinary albumin. METHODS: Three thousand eight hundred seventy-two patients with CKD classes IIIA-V had IMRS calculated retrospectively and survival analysis was performed investigating 1- and 5-year mortality. Kaplan-Meier survival curves were generated for predefined IMRS groups of low, medium and high risk for CKD patients overall and by sex and CKD stage. Serum phosphate and urinary albumin/creatinine ratios were modeled in multivariate Cox-proportional hazard models. Receiver operator characteristic curves were used to determine c statistics for mortality. RESULTS: For all patients with CKD, mortality was significantly greater for those with medium- or high-risk compared to low-risk IMRS categories, among each CKD stage. Overall, IMRS was predictive of mortality at both 1 and 5 years, even when adjusted for CKD stage and predicted mortality more accurately than CKD stage alone. Albuminuria was not independently associated with mortality and serum phosphate weakly predicted mortality. CONCLUSION: IMRS is a strong predictor of mortality in patients with CKD and is robustly complementary to CKD stage in refining risk prediction. Given the universal availability and low cost of the CBC and BMP, IMRS may be of a substantial value in CKD risk assessment and management. PMID- 26812217 TI - Obturator abscess with spread to the thigh muscles after a transobturator tension free vaginal tape. PMID- 26812218 TI - Uveitis and Systemic Inflammatory Markers in Convalescent Phase of Ebola Virus Disease. AB - We report a case of probable Zaire Ebola virus-related ophthalmologic complications in a physician from the United States who contracted Ebola virus disease in Liberia. Uveitis, immune activation, and nonspecific increase in antibody titers developed during convalescence. This case highlights immune phenomena that could complicate management of Ebola virus disease-related uveitis during convalescence. PMID- 26812219 TI - Good Amyloid, Bad Amyloid-What's the Difference? AB - Why do some amyloids cause serious neurodegenerative diseases, while others have important biological functions? A new study of the functional amyloid Orb2 suggests that it's all about speed. Read the Research Article. PMID- 26812220 TI - New cytotoxic phloroglucinols, baeckenones D-F, from the leaves of Indonesian Baeckea frutescens. AB - Three new phloroglucinols, baeckenones D-F (1-3), were obtained from the leaves of Indonesian Baeckea frutescens, along with the known unusual endoperoxide, phloroglucinol (4). The structures of the isolated compounds were elucidated by 1D and 2D NMR and HREIMS spectra. Furthermore, the stereochemistry of baeckenone D (1) was established by an X-ray diffraction analysis. Among the isolated compounds 1-4, baeckenone F (3) showed moderate cytotoxic activities against human pancreatic (PSN-1), lung (A549), and breast (MDA-MB-231) cancer cell lines, with IC50 values of 33.3 MUM, 34 MUM, and 39.3 MUM, respectively. PMID- 26812221 TI - Y(1-x)Sc(x)BaZn3GaO7 (0 <= x <= 1): Structure Evolution by Sc-Doping and the First Example of Photocatalytic Water Reduction in "114" Oxides. AB - "114" oxides have shown intriguing physical properties while their performance in photocatalysis has not yet been reported probably due to the instability in aqueous solution. YBaZn3GaO7 is an exception, which is stable and indeed shows observable photocatalytic H2 evolution (~2 MUmol/h/g) in methanol aqueous solution under UV light. This activity was enhanced to 23.6 MUmol/h/g by a full replacement of Y(3+) by Sc(3+). Optical absorption spectra and theoretical calculations show no significant difference upon Sc(3+)-doping. Instead, a systematic analysis of the structure evolution by Rietveld refinements for Y(1 x)Sc(x)BaZn3GaO7 (0 <= x <= 1) suggests that the increase of the catalytic activity is likely due to the decrease of the structural defects and thus the lower level of recombination rate of e(-) and h(+). In detail, Sc(3+) substitution leads to a shrinkage of YO6 octahedra, and successively the adjustment of the Zn(2+)/Ga(3+) occupancy behaviors in tetrahedra sites. The photocatalytic H2 evolution rate was further optimized to 118.2 MUmol/h/g in methanol solution and 42.9 MUmol/h/g in pure water for 1 wt % Pt-loaded ScBaZn3GaO7. Here, the relatively less investigated nonmagnetic "114" oxides were, for the first time, proved to be good candidates for photocatalytic water reduction. PMID- 26812223 TI - Second harmonic generation microscopy reveals hidden polar organization in fluoride doped MIL-53(Fe). AB - Polar metal-organic frameworks have potential applications as functional non linear optical, piezoelectric, pyroelectric and ferroelectric materials. Using second harmonic generation microscopy we found that fluoride doping of the microporous iron(iii) terephthalate MOF MIL-53(Fe) induces a polar organization in its structure, which was not previously detected with XRD. The polar order is only observed when both fluoride and guest molecules are present, and may be related to a complex interplay between the adsorbates and the framework, leading to a modification of the positioning of fluoride in the inorganic Fe-chains. Combined polarized second harmonic generation microscopy and scanning pyroelectric microscopy show that the polar axis is unidirectional and of the same sense over the whole crystal, extending up to 100 micrometers. This finding shows how MOF materials can be endowed with useful properties by doping MOFs with fluoride. PMID- 26812222 TI - Cumulated organ damage is associated with arterial stiffness in women with systemic lupus erythematosus irrespective of renal function. AB - OBJECTIVES: To determine whether there is an association between cumulated organ damage and arterial stiffness in women with systemic lupus erythematosus (SLE) with normal renal function and without renal damage. METHODS: Eighty-eight SLE women with normal renal function and without renal damage, and 102 sex- and age matched controls with no history of coronary heart disease or peripheral arterial disease were studied. Cumulated organ damage and arterial stiffness were measured using the SLICC/ACR Damage Index (SDI) and pulse wave velocity (PWV), respectively. Patients were categorised as with (SDI >=1) or without cumulated organ damage (SDI=0) and bivariate analyses were performed to compare both groups. A multivariate logistic regression was carried out to analyse the independent factors associated with cumulated organ damage. A multiple linear regression analysis was used to investigate the correlation between SDI and PWV, adjusted for appropriate confounders. RESULTS: PWV was significantly higher in patients with respect to controls (p=0.007). Also, patients with SDI >=1 had significantly higher PWV than those with SDI=0 (p=0.007). In the multivariate analysis, cumulated organ damage was significantly associated with PWV (p=0.006) and obesity (p=0.003). Furthermore, PWV correlated with SDI after adjustment for age, SLE duration, systolic blood pressure, body mass index, renal function, prednisone and homocysteine (r=0.283, p=0.011). Patients with increased PWV were more likely to have organ damage (SDI >=1) than those with normal PWV (67% vs. 36%, p=0.023). CONCLUSIONS: Cumulated organ damage was found to be independently associated with the arterial stiffness in SLE women without renal involvement. PMID- 26812224 TI - An in vitro reprogrammable antiviral RISC with size-preferential ribonuclease activity. AB - Infection of Nicotiana benthamiana plants with Tomato bushy stunt virus (TBSV) mutants compromised for silencing suppression induces formation of an antiviral RISC (vRISC) that can be isolated using chromatography procedures. The isolated vRISC sequence-specifically degrades TBSV RNA in vitro, its activity can be down regulated by removing siRNAs, and re-stimulated by exogenous supply of siRNAs. vRISC is most effective at hydrolyzing the ~4.8kb genomic RNA, but less so for a ~2.2kb TBSV subgenomic mRNA (sgRNA1), while the 3' co-terminal sgRNA2 of ~0.9kb appears insensitive to vRISC cleavage. Moreover, experiments with in vitro generated 5' co-terminal viral transcripts show that RNAs of ~2.7kb are efficiently cleaved while those of ~1.1kb or shorter are unaffected. The isolated antiviral ribonuclease complex fails to degrade ~0.4kb defective interfering RNAs (DIs) in vitro, agreeing with findings that in plants DIs are not targeted by silencing. PMID- 26812225 TI - Association between Hepatic Triglyceride Content and Left Ventricular Diastolic Function in a Population-based Cohort: The Netherlands Epidemiology of Obesity Study. AB - PURPOSE: To investigate the association between hepatic triglyceride content and left ventricular (LV) diastolic function while taking potential confounding factors into account, including the components of the metabolic syndrome. MATERIALS AND METHODS: The study was approved by the institutional review board, and all participants gave informed consent. In this cross-sectional analysis of baseline data from the Netherlands Epidemiology of Obesity study, a population based, prospective cohort study, participants (45% men; mean age +/- standard deviation, 55.3 years +/- 6.2) underwent magnetic resonance (MR) spectroscopy and MR imaging to assess hepatic triglyceride content and LV diastolic heart function (ratio of peak filling rates of the early filling phase and atrial contraction [E/A ratio]). Multivariate linear regression analysis was performed while adjusting for confounding factors, and results were additionally stratified according to body mass index. RESULTS: Adjustment for age, sex, heart rate, alcohol consumption, pack-years of smoking, all components of the metabolic syndrome, and visceral adiposity attenuated crude observed associations. A 10 fold increase in hepatic triglyceride content was associated with a change in mean E/A ratio of -0.004 (95% confidence interval [CI]: -0.134, 0.125) in the total study population, -0.194 (95% CI: -0.430, 0.042) in the normal-weight subgroup, 0.079 (95% CI: -0.090, 0.248) in the overweight subgroup, and -0.109 (95% CI: -0.186, -0.032) in the obese subgroup. CONCLUSION: Fatty liver itself could, at least in obesity, pose a risk of myocardial dysfunction above and beyond known cardiovascular risk factors that are clustered within the metabolic syndrome. The association in the obese subgroup was small, and future studies with larger samples sizes are required to investigate to what extent the association exists and differs in normal-weight, overweight, and obese persons to unravel its clinical relevance. PMID- 26812226 TI - New Year's note 2016. PMID- 26812227 TI - Cytometry Part A Software Policy. PMID- 26812228 TI - Publishing code is essential for reproducible flow cytometry bioinformatics. PMID- 26812230 TI - Automated analysis of flow cytometry data comes of age. PMID- 26812231 TI - Trematode Fluke Procerovum varium as Cause of Ocular Inflammation in Children, South India. AB - Trematodes are recognized as a group of emerging parasites in tropical countries. We identified a trematode as a cause of ocular granulomas that developed in children who bathed in ponds or rivers in South India. DNA was isolated from patients' surgically excised granulomas and from the trematode cercariae (larvae) released by the snail Melanoides tuberculata in water in which the children bathed. Real-time and conventional PCRs were performed that targeted ribosomal DNA regions spanning the internal transcribed spacer 2 and 28S sequences of this trematode. The PCR-amplified products were subjected to bidirectional sequencing. Analysis of sequences for the granuloma samples and the trematode cercariae showed maximum sequence similarity with Procerovum varium (family Heterophyidae). Our results confirmed the etiology of the ocular infection, implicating snail vectors as environmental risk factors for ocular parasitosis. PMID- 26812232 TI - Cholesterol Extraction from Cell Membrane by Graphene Nanosheets: A Computational Study. AB - The health risk associated with high cholesterol levels in the human body has motivated intensive efforts to lower them by using specialized drugs. However, little research has been reported on utilizing nanomaterials to extract extra cholesterol from living tissues. Graphene possesses great potential for cholesterol extraction from cell membranes due to its distinct porous structure and outstanding surface adhesion. Here we employ dissipative dynamic simulations to explore pathways for cholesterol extraction from a cell membrane by a sheet of graphene using a coarse-grained graphene nanosheets (CGGN) model. We first demonstrate that the self-assembly process among a single layer of graphene and a group of randomly distributed cholesterol molecules in the aqueous environment, which provides a firm foundation for graphene-cholesterol interactions and the dynamic cholesterol extraction process from the cell membrane. Simulations results show that graphene is capable of removing cholesterol molecules from the bilayer membrane. The interaction between graphene and cholesterol molecules plays an important role in determining the amount of extracted cholesterol molecules from the cell membrane. Our findings open up a promising avenue to exploit the capability of graphene for biomedical applications. PMID- 26812233 TI - Pyridine derivative/graphene nanoribbon composites as molecularly tunable heterogeneous electrocatalysts for the oxygen reduction reaction. AB - In this study, a strategy to design a new class of metal-free electrocatalysts for the oxygen reduction reaction (ORR) was proposed by means of density functional theory (DFT) computations. The electrocatalysts consist of various pyridine derivatives that are anchored on the edge sites of armchair graphene nanoribbons (AGNRs). Our results revealed that these anchored pyridine derivatives have considerably high stability, and the C atoms around the "external" N-dopant possess the largest positive charge, thus facilitating the ORR though a more efficient 4e pathway, in which the first electron is transferred into O2 molecules over a long range in the outer Helmholtz plane (i.e., the ET-OHP mechanism). Among these designed catalysts, the pyrimidine/AGNR exhibits the highest catalytic activity, which can be comparable to that of Pt based catalysts. Therefore, our computations suggested that the combination of pyridine derivatives with graphene nanoribbons can constitute a novel and well defined heterogeneous electrocatalyst with good stability and tunable active sites for the ORR, which provides a useful guidance to develop the next generation of low-cost and metal-free electrocatalysts with accurate N species and content for the ORR in fuel cells. PMID- 26812234 TI - Hydrogen-Bonding Network Promoted [3+2] Cycloaddition: Asymmetric Catalytic Construction of Spiro-pseudoindoxyl Derivatives. AB - The enantioselective construction of a spirocyclic quaternary stereogenic carbon center at the C2 position of indole has long been an elusive problem in organic synthesis. Herein, by employing a rationally designed hydrogen-bonding network activation strategy, for the first time, 2,2'-pyrrolidinyl-spirooxindole, which is a valuable and prevalent indole alkaloid scaffold, was directly obtained through a catalytic asymmetric [3+2] cycloaddition reaction with high yields and excellent stereoselectivities. PMID- 26812235 TI - Modeling the Internet of Things, Self-Organizing and Other Complex Adaptive Communication Networks: A Cognitive Agent-Based Computing Approach. AB - BACKGROUND: Computer Networks have a tendency to grow at an unprecedented scale. Modern networks involve not only computers but also a wide variety of other interconnected devices ranging from mobile phones to other household items fitted with sensors. This vision of the "Internet of Things" (IoT) implies an inherent difficulty in modeling problems. PURPOSE: It is practically impossible to implement and test all scenarios for large-scale and complex adaptive communication networks as part of Complex Adaptive Communication Networks and Environments (CACOONS). The goal of this study is to explore the use of Agent based Modeling as part of the Cognitive Agent-based Computing (CABC) framework to model a Complex communication network problem. METHOD: We use Exploratory Agent based Modeling (EABM), as part of the CABC framework, to develop an autonomous multi-agent architecture for managing carbon footprint in a corporate network. To evaluate the application of complexity in practical scenarios, we have also introduced a company-defined computer usage policy. RESULTS: The conducted experiments demonstrated two important results: Primarily CABC-based modeling approach such as using Agent-based Modeling can be an effective approach to modeling complex problems in the domain of IoT. Secondly, the specific problem of managing the Carbon footprint can be solved using a multiagent system approach. PMID- 26812237 TI - C-reactive protein inhibits high-molecular-weight adiponectin expression in 3T3 L1 adipocytes via PI3K/Akt pathway. AB - Adiponectin, an adipose-specific protein hormone, is secreted from white adipose tissue and involved in glucose and lipid metabolism. It is assembled into low molecular-weight trimer (LMW), middle-molecular-weight hexameric (MMW) and high molecular-weight (HMW), among which HMW exhibits higher activity. In this study, we proved that C-reactive protein (CRP), an inflammatory marker, inhibited adiponectin expression, especially HMW in time-and dose-dependent manners. Furthermore, CRP decreased the HMW/total adiponectin ration and reduced adiponectin assembly by increasing ERp44, and decreasing Ero1-alpha and DsbA-L. CRP activated pAkt, the downstream of PI3K. Inhibition of PI3K or pAkt abolished the effect of CRP. Our study suggested that CRP decreased adiponectin expression and multimerization, while CRP-induced decline in adiponectin might be mediated through the PI3K/Akt pathway. PMID- 26812236 TI - Strategies to Prevent Cholera Introduction during International Personnel Deployments: A Computational Modeling Analysis Based on the 2010 Haiti Outbreak. AB - BACKGROUND: Introduction of Vibrio cholerae to Haiti during the deployment of United Nations (UN) peacekeepers in 2010 resulted in one of the largest cholera epidemics of the modern era. Following the outbreak, a UN-commissioned independent panel recommended three pre-deployment intervention strategies to minimize the risk of cholera introduction in future peacekeeping operations: screening for V. cholerae carriage, administering prophylactic antimicrobial chemotherapies, or immunizing with oral cholera vaccines. However, uncertainty regarding the effectiveness of these approaches has forestalled their implementation by the UN. We assessed how the interventions would have impacted the likelihood of the Haiti cholera epidemic. METHODS AND FINDINGS: We developed a stochastic model for cholera importation and transmission, fitted to reported cases during the first weeks of the 2010 outbreak in Haiti. Using this model, we estimated that diagnostic screening reduces the probability of cases occurring by 82% (95% credible interval: 75%, 85%); however, false-positive test outcomes may hamper this approach. Antimicrobial chemoprophylaxis at time of departure and oral cholera vaccination reduce the probability of cases by 50% (41%, 57%) and by up to 61% (58%, 63%), respectively. Chemoprophylaxis beginning 1 wk before departure confers a 91% (78%, 96%) reduction independently, and up to a 98% reduction (94%, 99%) if coupled with vaccination. These results are not sensitive to assumptions about the background cholera incidence rate in the endemic troop sending country. Further research is needed to (1) validate the sensitivity and specificity of rapid test approaches for detecting asymptomatic carriage, (2) compare prophylactic efficacy across antimicrobial regimens, and (3) quantify the impact of oral cholera vaccine on transmission from asymptomatic carriers. CONCLUSIONS: Screening, chemoprophylaxis, and vaccination are all effective strategies to prevent cholera introduction during large-scale personnel deployments such as that precipitating the 2010 Haiti outbreak. Antimicrobial chemoprophylaxis was estimated to provide the greatest protection at the lowest cost among the approaches recently evaluated by the UN. PMID- 26812238 TI - Reference Charts for Fetal Cerebellar Vermis Height: A Prospective Cross Sectional Study of 10605 Fetuses. AB - OBJECTIVE: To establish reference charts for fetal cerebellar vermis height in an unselected population. METHODS: A prospective cross-sectional study between September 2009 and December 2014 was carried out at ALTAMEDICA Fetal-Maternal Medical Centre, Rome, Italy. Of 25203 fetal biometric measurements, 12167 (48%) measurements of the cerebellar vermis were available. After excluding 1562 (12.8%) measurements, a total of 10605 (87.2%) fetuses were considered and analyzed once only. Parametric and nonparametric quantile regression models were used for the statistical analysis. In order to evaluate the robustness of the proposed reference charts regarding various distributional assumptions on the ultrasound measurements at hand, we compared the gestational age-specific reference curves we produced through the statistical methods used. Normal mean height based on parametric and nonparametric methods were defined for each week of gestation and the regression equation expressing the height of the cerebellar vermis as a function of gestational age was calculated. Finally the correlation between dimension/gestation was measured. RESULTS: The mean height of the cerebellar vermis was 12.7mm (SD, 1.6mm; 95% confidence interval, 12.7-12.8mm). The regression equation expressing the height of the CV as a function of the gestational age was: height (mm) = -4.85+0.78 x gestational age. The correlation between dimension/gestation was expressed by the coefficient r = 0.87. CONCLUSION: This is the first prospective cross-sectional study on fetal cerebellar vermis biometry with such a large sample size reported in literature. It is a detailed statistical survey and contains new centile-based reference charts for fetal height of cerebellar vermis measurements. PMID- 26812239 TI - Identification of Putative Chemosensory Receptor Genes from the Athetis dissimilis Antennal Transcriptome. AB - Olfaction plays a crucial role in insect population survival and reproduction. Identification of the genes associated with the olfactory system, without the doubt will promote studying the insect chemical communication system. In this study, RNA-seq technology was used to sequence the antennae transcriptome of Athetis dissimilis, an emerging crop pest in China with limited genomic information, with the purpose of identifying the gene set involved in olfactory recognition. Analysis of the transcriptome of female and male antennae generated 13.74 Gb clean reads in total from which 98,001 unigenes were assembled, and 25,930 unigenes were annotated. Total of 60 olfactory receptors (ORs), 18 gustatory receptors (GRs), and 12 ionotropic receptors (IRs) were identified by Blast and sequence similarity analyzes. One obligated olfactory receptor co receptor (Orco) and four conserved sex pheromone receptors (PRs) were annotated in 60 ORs. Among the putative GRs, five genes (AdisGR1, 6, 7, 8 and 94) clustered in the sugar receptor family, and two genes (AdisGR3 and 93) involved in CO2 detection were identified. Finally, AdisIR8a.1 and AdisIR8a.2 co-receptors were identified in the group of candidate IRs. Furthermore, expression levels of these chemosensory receptor genes in female and male antennae were analyzed by mapping the Illumina reads. PMID- 26812240 TI - A Generic Polymer-Protein Ligation Strategy for Vaccine Delivery. AB - Although the field of cancer immunotherapy is intensively investigated, there is still a need for generic strategies that allow easy, mild and efficient formulation of vaccine antigens. Here we report on a generic polymer-protein ligation strategy to formulate protein antigens into reversible polymeric conjugates for enhanced uptake by dendritic cells and presentation to CD8 T cells. A N-hydroxypropylmethacrylamide (HPMA)-based copolymer was synthesized via RAFT polymerization followed by introduction of pyridyldisulfide moieties. To enhance ligation efficiency to ovalbumin, which is used as a model protein antigen, protected thiols were introduced onto lysine residues and deprotected in situ in the presence of the polymer. The ligation efficiency was compared for both the thiol-modified versus unmodified ovalbumin, and the reversibility was confirmed. Furthermore, the obtained nanoconjugates were tested in vitro for their interaction and association with dendritic cells, showing enhanced cellular uptake and antigen cross-presentation to CD8 T-cells. PMID- 26812241 TI - Influence of Solution Chemistry and Soft Protein Coronas on the Interactions of Silver Nanoparticles with Model Biological Membranes. AB - The influence of solution chemistry and soft protein coronas on the interactions between citrate-coated silver nanoparticles (AgNPs) and model biological membranes was investigated by assembling supported lipid bilayers (SLBs) composed of zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) on silica crystal sensors in a quartz crystal microbalance with dissipation monitoring (QCM-D). Our results show that the deposition rates of AgNPs on unmodified silica surfaces increased with increasing electrolyte concentrations under neutral pH conditions. Similar trends were observed when AgNPs were deposited on SLBs, hence indicating that the deposition of AgNPs on model cell membranes was controlled by electrostatic interactions. In the presence of human serum albumin (HSA) proteins at both pH 7 and pH 2, the colloidal stability of AgNPs was considerably enhanced due to the formation of HSA soft coronas surrounding the nanoparticles. At pH 7, the deposition of AgNPs on SLBs was suppressed in the presence of HSA due to steric repulsion between HSA-modified AgNPs and SLBs. In contrast, pronounced deposition of HSA-modified AgNPs on SLBs was observed at pH 2. This observation was attributed to the reduction of electrostatic repulsion as well as conformation changes of adsorbed HSA under low pH conditions, resulting in the decrease of steric repulsion between AgNPs and SLBs. PMID- 26812242 TI - Formation, Fragmentation, and Structures of YxOy(+) (x = 1, 2, y = 1 - 13) Clusters: Collision-Induced Dissociation Experiments and Density Functional Theory Calculations. AB - Yttrium oxide cluster cations have been experimentally and theoretically studied. We produced small, oxygen-rich yttrium oxide clusters, YxOy+ (x = 1, 2, y = 1 13), by mixing the laser-produced yttrium plasma with a molecular oxygen jet. Mass spectrometry measurements showed that the most stable clusters are those consisting of one yttrium and an odd number of oxygen atoms of the form YO(+)(2k+1) (k = 0-6). Additionally, we performed collision induced dissociation experiments, which indicated that the loss of pairs of oxygen atoms down to a YO+ core is the preferred fragmentation channel for all clusters investigated. Furthermore, we conduct DFT calculations and we obtained two types of low-energy structures: one containing an yttrium cation core and the other composed of YO+ core and O2 ligands, being in agreement with the observed fragmentation pattern. Finally, from the fragmentation studies, total collision cross sections are obtained and these are compared with geometrical cross sections of the calculated structures. PMID- 26812243 TI - Association of the very early rise of human chorionic gonadotropin with adverse outcomes in singleton pregnancies after in vitro fertilization. AB - OBJECTIVE: To determine if very early serum hCG, a marker of trophoblast differentiation, is associated with adverse perinatal outcomes in singleton pregnancies. DESIGN: Retrospective cohort study. SETTING: University fertility program. PATIENT(S): A total of 360 singleton IVF live births. INTERVENTION(S): Serial hCG measurements were used to determine the within-woman slope for hCG (hCG rise). MAIN OUTCOMES MEASURE(S): Primary outcomes included birth weight and gestational age at delivery. Statistical comparisons used t test, chi-square test, and linear and logistic regressions as appropriate. RESULT(S): hCG rise was positively associated with birth weight but not gestational age at delivery. Infant sex, gestational age, and type of embryo transfer (fresh vs. frozen/thawed) were significantly associated with birth weight and confounded the associations of interest. hCG rise was slower among subjects delivering an infant with low birth weight (slope 0.386 +/- 0.05 vs. 0.407 +/- 0.06) or small for gestational age (slope 0.371 +/- 0.07 vs. 0.406 +/- 0.06). Analysis of hCG rise by quartile showed that, compared with the first quartile (slowest), subjects with a rate of hCG rise in the fourth quartile (fastest) had a significantly decreased risk of delivering an infant of low birth weight. No relationship was noted between hCG rise and hypertensive disorders of pregnancy. CONCLUSION(S): Slower very early first-trimester hCG rise is associated with low birth weight but not gestational age at delivery among singleton IVF conceptions. The rate of increase in serum hCG may reflect early trophoblast differentiation and placentation and, possibly, may predict subsequent development. PMID- 26812244 TI - Aging and the environment affect gamete and embryo potential: can we intervene? AB - Optimal maturation of the oocyte depends on its environment and determines embryo competence, because the embryonic genome is not active until the cleavage stage and new mitochondria are not produced until blastulation. Adverse environmental factors include aging, andropause, oxidative stress, obesity, smoking, alcohol, and psychologic stress, whereas androgen supplementation, a prudent diet, exercise, nutritional supplements, and psychologic interventions have beneficial effects. Mitochondrial function and energy production deteriorate with age, adversely affecting ovarian reserve, chromosome segregation, and embryo competence. In aging mice, the mitochondrial cofactor coenzyme Q10 reverses most of these changes. Early human experience has been encouraging, although only a small study using a shorter duration of intervention compared with the murine model has been carried out. Mitochondrial metabolic stress can result in an abnormal compensatory increase in mitochondrial DNA, which can be assessed in biopsied blastomeres of trophectoderm as a predictive biomarker of implantation failure. Psychologic stress may reduce oocyte competence by shifting blood flow away from the ovary as part of the classic "fight or flight" physiologic response, and methods to reduce stress or the body's reaction to stress improve pregnancy success. Enhancing oocyte competence is a key intervention that promises to reduce the number of euploid embryos failing to produce viable deliveries. PMID- 26812245 TI - Cited2 protein level in cumulus cells is a biomarker for human embryo quality and pregnancy outcome in one in vitro fertilization cycle. AB - OBJECTIVE: To determine whether the levels of CBP/p300 interacting transactivator with ED-rich tail 2 (Cited2) protein in cumulus cells (CCs) derived from patients undergoing IVF related to infertility factors, embryo quality, and clinical outcomes in one IVF cycle. DESIGN: Retrospective analysis of human CCs. SETTING: Public hospital and university. PATIENT(S): A total of 103 (conventional) IVF patients and 32 intracytoplasmic sperm injection patients. INTERVENTION(S): All CCs from each patient's oocytes were considered as one sample. The patients were divided into two groups according to whether the Cited2/beta-actin levels in their CCs were above or below the mean level detected for all patients. MAIN OUTCOME MEASURE(S): Embryo quality and clinical outcomes of IVF patients. RESULT(S): The oocytes derived from the group of patients whose CCs showed lower Cited2 levels displayed higher fertilization, transferable embryo, and implantation rates. Moreover, the patients in this group were more likely to have a successful pregnancy outcome. Among different infertility factors, a total of 78.6% of patients with polycystic ovary syndrome had a higher Cited2 level in CCs. Additionally, patients with a lower basal FSH level belonged to the higher Cited2 levels group. The expression of two genes (phosphoenolpyruvate carboxykinase 1 [PCK1] and progesterone receptor [PR]) and the glucose content in CCs were also markedly increased in CCs derived from patients with higher Cited2 levels. CONCLUSION(S): The present findings imply that Cited2 level in CCs is associated with polycystic ovary syndrome, embryo quality, and pregnancy outcome of IVF patients. PMID- 26812246 TI - Smoking-Related Home Oxygen Burn Injuries: Continued Cause for Alarm. AB - BACKGROUND: Home oxygen therapy is a mainstay of treatment for patients with various cardiopulmonary diseases. In spite of warnings against smoking while using home oxygen, many patients sustain burn injuries. OBJECTIVES: We aimed to quantify the morbidity and mortality of such patients admitted to our regional burn unit over a 6-year period. METHODS: A retrospective chart review of all patients admitted to a regional burn center from 2008 through 2013 was completed. Admitted patients sustaining burns secondary to smoking while using home oxygen therapy were selected as the study population to determine morbidity. RESULTS: Fifty-five subjects were admitted to the burn unit for smoking-related home oxygen injuries. The age range was 40-84 years. Almost all subjects were on home oxygen for chronic obstructive pulmonary disease (96%). Seventy-two percent of burns involved <5% of the total body surface area, 51% of patients were intubated, and of those 33% had evidence of inhalation injury. The hospital mortality rate was 14.5%. The mean length of hospital stay was 8.6 days, and 54.5% were discharged to a nursing home or another advanced facility. Finally, concomitant substance abuse was found in 27%, and a previous history of injury from smoking while on home oxygen was discovered in 14.5%. CONCLUSIONS: This single-center analysis is one of the largest describing burn injuries stemming from smoking while using home oxygen therapy. We identified the morbidity and mortality associated with these injuries. Ongoing education and careful consideration of prescribing home oxygen therapy for known smokers is highly encouraged. PMID- 26812247 TI - Reliability and Discriminative Ability of a New Method for Soccer Kicking Evaluation. AB - The study aimed to evaluate the test-retest reliability of a newly developed 356 Soccer Shooting Test (356-SST), and the discriminative ability of this test with respect to the soccer players' proficiency level and leg dominance. Sixty-six male soccer players, divided into three groups based on their proficiency level (amateur, n = 24; novice semi-professional, n = 18; and experienced semi professional players, n = 24), performed 10 kicks following a two-step run up. Forty-eight of them repeated the test on a separate day. The following shooting variables were derived: ball velocity (BV; measured via radar gun), shooting accuracy (SA; average distance from the ball-entry point to the goal centre), and shooting quality (SQ; shooting accuracy divided by the time elapsed from hitting the ball to the point of entry). No systematic bias was evident in the selected shooting variables (SA: 1.98+/-0.65 vs. 2.00+/-0.63 m; BV: 24.6+/-2.3 vs. 24.5+/ 1.9 m s-1; SQ: 2.92+/-1.0 vs. 2.93+/-1.0 m s-1; all p>0.05). The intra-class correlation coefficients were high (ICC = 0.70-0.88), and the coefficients of variation were low (CV = 5.3-5.4%). Finally, all three 356-SST variables identify, with adequate sensitivity, differences in soccer shooting ability with respect to the players' proficiency and leg dominance. The results suggest that the 356-SST is a reliable and sensitive test of specific shooting ability in men's soccer. Future studies should test the validity of these findings in a fatigued state, as well as in other populations. PMID- 26812248 TI - N-acetylcysteine attenuates nicotine-induced kindling in female periadolescent rats. AB - Kindling is a form of behavioral sensitization that is related to the progression of several neuropsychiatric disorders such as bipolar disorder. We recently demonstrated that female periadolescent rats are more vulnerable to nicotine (NIC)-induced kindling than their male counterparts. Furthermore, we evidenced that decreases in brain antioxidative defenses may contribute to this gender difference. Here we aimed to determine the preventive effects of the antioxidant N-acetyl cysteine (NAC) against NIC-kindling in female periadolescent rats. To do this female Wistar rats at postnatal day 30 received repeated injections of NIC 2mg/kg, i.p. every weekday for up to 19 days. NAC90, 180 or 270 mg/kg, i.p. was administered 30 min before NIC. The levels of glutathione (GSH), superoxide dismutase (SOD) activity, lipid peroxidation (LP) and nitrite were determined in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST). The development of kindling occurred at a median time of 16.5 days with 87.5% of NIC animals presenting stage 5 seizures in the last day of drug administration. NAC270 prevented the occurrence of kindling. NIC-kindled animals presented decreased levels of GSH and increased LP in the PFC, HC and ST, while SOD activity was decreased in the ST. NAC180 or 270 prevented the alterations in GSH induced by NIC, but only NAC270 prevented the alterations in LP. Nitrite levels increased in the ST of NAC270 pretreated NIC-kindled animals. Taken together we demonstrated that NAC presents anti-kindling effects in female animals partially through the restoration of oxidative alterations. PMID- 26812249 TI - Is there a difference between stripy journeys and stripy ladybirds? The N400 response to semantic and world-knowledge violations during sentence processing. AB - The distinction between linguistic and non-linguistic knowledge is particularly relevant because it is related to the principle of compositionality during sentence comprehension. Hagoort, Hald, Bastiaansen, and Petersson (2004) challenged the distinction between linguistic and non-linguistic knowledge. Here, we investigate how linguistic and non-linguistic violations are processed in a setting adapted from Hagoort et al., whilst in contrast to Hagoort, keeping the critical word identical. In line with the findings by Hagoort et al., our results showed largest N400 amplitudes for semantic violations ('Journeys are stripy'), followed by non-linguistic world-knowledge violations ('Ladybirds are stripy') and contingent sentences ('Trousers are stripy'), and finally by correct sentences ('Zebras are stripy'). Traditional fractional area and relative criterion measures of peak and onset latencies showed no effect of violation type. Interestingly, the semantic violation condition crossed a fixed criterion earlier than the word-knowledge violation condition. In conclusion, our data suggests that the question regarding the distinction between linguistic- and non linguistic knowledge in terms of language integration remains open. Implications for future studies addressing the difference between linguistic and non linguistic knowledge are discussed. PMID- 26812250 TI - Effects of empathic social responses on the emotions of the recipient. AB - Empathy is highly relevant for social behavior and can be verbally expressed by voicing sympathy and concern (emotional empathy) as well as by paraphrasing or stating that one can mentally reconstruct and understand another person's thoughts and feelings (cognitive empathy). In this study, we investigated the emotional effects and neural correlates of receiving empathic social responses after negative performance feedback and compared the effects of emotionally vs. cognitively empathic comments. 20 participants (10 male) underwent functional magnetic resonance imaging while receiving negative performance feedback for a cognitive task. Performance feedback was followed by verbal comments either expressing cognitive and emotional empathy or demonstrating a lack of empathy. Empathic comments in general led to less negative self-reported feelings and calmer breathing. At the neural level, empathic comments induced activity in regions associated with social cognition and emotion processing, specifically in right postcentral gyrus and left cerebellum (cognitively empathic comments), right precentral gyrus, the opercular part of left inferior frontal gyrus, and left middle temporal gyrus (emotionally empathic comments), as well as the orbital part of the left middle frontal gyrus and left superior parietal gyrus (emotionally empathic vs. unempathic comments). The study shows that cognitively and emotionally empathic comments appear to be processed in partially separable neural systems. Furthermore, confirming and expanding on another study on the same subject, the present results demonstrate that the social display of cognitive empathy exerts almost as positive effects on the recipient's feelings and emotions in states of distress as emotionally empathic response does. This can be relevant for professional settings in which strong negative emotions need to be de-escalated while maintaining professional impartiality, which may allow the display of cognitive but not emotional empathy. PMID- 26812251 TI - An Alzheimer's Disease-Derived Biomarker Signature Identifies Parkinson's Disease Patients with Dementia. AB - Biomarkers from multiple modalities have been shown to correlate with cognition in Parkinson's disease (PD) and in Alzheimer's disease (AD). However, the relationships of these markers with each other, and the use of multiple markers in concert to predict an outcome of interest, are areas that are much less explored. Our objectives in this study were (1) to evaluate relationships among 17 biomarkers previously reported to associate with cognition in PD or AD and (2) to test performance of a five-biomarker classifier trained to recognize AD in identifying PD with dementia (PDD). To do this, we evaluated a cross-sectional cohort of PD patients (n = 75) across a spectrum of cognitive abilities. All PD participants had 17 baseline biomarkers from clinical, genetic, biochemical, and imaging modalities measured, and correlations among biomarkers were assessed by Spearman's rho and by hierarchical clustering. We found that internal correlation among all 17 candidate biomarkers was modest, showing a maximum pairwise correlation coefficient of 0.51. However, a five-marker subset panel derived from AD (CSF total tau, CSF phosphorylated tau, CSF amyloid beta 42, APOE genotype, and SPARE-AD imaging score) discriminated cognitively normal PD patients vs. PDD patients with 80% accuracy, when employed in a classifier originally trained to recognize AD. Thus, an AD-derived biomarker signature may identify PDD patients with moderately high accuracy, suggesting mechanisms shared with AD in some PDD patients. Based on five measures readily obtained during life, this AD-derived signature may prove useful in identifying PDD patients most likely to respond to AD-based crossover therapies. PMID- 26812253 TI - What's the Point?: A Review of Reward Systems Implemented in Gamification Interventions. AB - Rewards are commonly used in interventions to change behavior, but they can inhibit development of intrinsic motivation, which is associated with long-term behavior maintenance. Gamification is a novel intervention strategy that may target intrinsic motivation through fun and enjoyment. Before the effects of gamified interventions on motivation can be determined, there must be an understanding of how gamified interventions operationalize rewards, such as point systems. The purpose of this review is to determine the prevalence of different reward types, specifically point systems, within gamified interventions. Electronic databases were searched for relevant articles. Data sources included Medline OVID, Medline PubMed, Web of Science, CINAHL, Cochrane Central, and PsycINFO. Out of the 21 articles retrieved, 18 studies described a reward system and were included in this review. Gamified interventions were designed to target a myriad of clinical outcomes across diverse populations. Rewards included points (n = 14), achievements/badges/medals (n = 7), tangible rewards (n = 7), currency (n = 4), other unspecified rewards (n = 3), likes (n = 2), animated feedback (n = 1), and kudos (n = 1). Rewards, and points in particular, appear to be a foundational component of gamified interventions. Despite their prevalence, authors seldom described the use of noncontingent rewards or how the rewards interacted with other game features. The reward systems relying on tangible rewards and currency may have been limited by inhibited intrinsic motivation. As gamification proliferates, future research should explicitly describe how rewards were operationalized in the intervention and evaluate the effects of gamified rewards on motivation across populations and research outcomes. PMID- 26812252 TI - Severity of fibromyalgia symptoms is associated with socioeconomic status and not obesity in Korean patients. AB - OBJECTIVES: Several studies conducted in Western countries have shown that obese or overweight patients with fibromyalgia (FM) exhibit more severe symptoms than patients of normal weight. However, there has been no study on the relationship between obesity and FM symptom severity in Asian patients. In this study, we evaluated the association between obesity, and other related factors such as socioeconomic status (SES), and FM symptom severity in Korean patients. METHODS: A total of 343 participants were enrolled in this prospective cohort study, which used a nationwide survey of FM patients who were followed on an annual basis. We investigated health-related quality of life (QoL) and associated factors, such as demographic characteristics, SES, and physical and psychological function. The FM patients were assessed using the following self-reported questionnaires: the Medical Outcomes Study Short-Form Health Survey, the Fibromyalgia Impact Questionnaire, the Brief Fatigue Inventory, the Beck Depression Inventory, the State-Trait Anxiety Inventory, the Self-Efficacy Scale, and the Social Support Scale. RESULTS: Of the 343 patients, 76 (22.1%) were obese; these patients did not differ from the non-obese patients in terms of tender points or self-reported questionnaire scores. FM patients with lower SES - as indexed by unemployment, lower income, and education levels - had more severe symptoms, and poorer QoL and function compared to those with higher SES. CONCLUSIONS: In contrast to Western patients, symptom severity in Korean FM patients is associated with SES, but not with obesity. PMID- 26812254 TI - N-3 Polyunsaturated Fatty Acids of Marine Origin and Multifocality in Human Breast Cancer. AB - OBJECTIVE: The microenvironment of breast epithelial tissue may contribute to the clinical expression of breast cancer. Breast epithelial tissue, whether healthy or tumoral, is directly in contact with fat cells, which in turn could influence tumor multifocality. In this pilot study we investigated whether the fatty acid composition of breast adipose tissue differed according to breast cancer focality. METHODS: Twenty-three consecutive women presenting with non-metastatic breast cancer underwent breast-imaging procedures including Magnetic Resonance Imaging prior to treatment. Breast adipose tissue specimens were collected during breast surgery. We established a biochemical profile of adipose tissue fatty acids by gas chromatography. We assessed whether there were differences according to breast cancer focality. RESULTS: We found that decreased levels in breast adipose tissue of docosahexaenoic and eicosapentaenoic acids, the two main polyunsaturated n-3 fatty acids of marine origin, were associated with multifocality. DISCUSSION: These differences in lipid content may contribute to mechanisms through which peritumoral adipose tissue fuels breast cancer multifocality. PMID- 26812256 TI - From the Editors. PMID- 26812255 TI - Effect of polyamines on the grain filling of wheat under drought stress. AB - Drought inhibits wheat grain filling. Polyamines (PAs) are closely associated with plant resistance due to drought and grain filling of cereals. However, little is known about the effect of PAs on the grain filling of wheat under drought stress. This study investigated whether and how PAs are involved in regulating wheat grain filling under drought stress. Two wheat genotypes differing in drought resistance were used, and endogenous PA levels were measured during grain filling under different water treatments. Additionally, external PAs were used, and the variation of hormone levels in grains was measured during grain filling under drought stress. The results indicated that spermidine (Spd) and spermine (Spm) relieve the inhibition caused by drought stress, and putrescine (Put) has the opposite effect. The higher activities of S adenosylmethionine decarboxylase and Spd synthase in grains promotes the synthetic route from Put to Spd and Spm and notably increases the free Spd and Spm concentrations in grains, which promotes grain filling and drought resistance in wheat. The effect of PA on the grain filling of wheat under drought stress was closely related to the endogenous ethylene (ETH), zeatin (Z) + zeatin riboside (ZR) and abscisic acid (ABA). Spd and Spm significantly increased the Z + ZR and ABA concentrations and decreased the ETH evolution rate in grains, which promoted wheat grain filling under drought. Put significantly increased the ETH evolution rate, which led to excessive ABA accumulation in grains, subsequently aggravating the inhibition of drought on wheat grain filling. This means that the interaction of hormones, rather than the action of a single hormone, was involved in the regulation of wheat grain filling under drought. PMID- 26812257 TI - QMRA for Drinking Water: 1. Revisiting the Mathematical Structure of Single-Hit Dose-Response Models. AB - Dose-response models are essential to quantitative microbial risk assessment (QMRA), providing a link between levels of human exposure to pathogens and the probability of negative health outcomes. In drinking water studies, the class of semi-mechanistic models known as single-hit models, such as the exponential and the exact beta-Poisson, has seen widespread use. In this work, an attempt is made to carefully develop the general mathematical single-hit framework while explicitly accounting for variation in (1) host susceptibility and (2) pathogen infectivity. This allows a precise interpretation of the so-called single-hit probability and precise identification of a set of statistical independence assumptions that are sufficient to arrive at single-hit models. Further analysis of the model framework is facilitated by formulating the single-hit models compactly using probability generating and moment generating functions. Among the more practically relevant conclusions drawn are: (1) for any dose distribution, variation in host susceptibility always reduces the single-hit risk compared to a constant host susceptibility (assuming equal mean susceptibilities), (2) the model-consistent representation of complete host immunity is formally demonstrated to be a simple scaling of the response, (3) the model-consistent expression for the total risk from repeated exposures deviates (gives lower risk) from the conventional expression used in applications, and (4) a model-consistent expression for the mean per-exposure dose that produces the correct total risk from repeated exposures is developed. PMID- 26812258 TI - QMRA for Drinking Water: 2. The Effect of Pathogen Clustering in Single-Hit Dose Response Models. AB - Spatial and/or temporal clustering of pathogens will invalidate the commonly used assumption of Poisson-distributed pathogen counts (doses) in quantitative microbial risk assessment. In this work, the theoretically predicted effect of spatial clustering in conventional "single-hit" dose-response models is investigated by employing the stuttering Poisson distribution, a very general family of count distributions that naturally models pathogen clustering and contains the Poisson and negative binomial distributions as special cases. The analysis is facilitated by formulating the dose-response models in terms of probability generating functions. It is shown formally that the theoretical single-hit risk obtained with a stuttering Poisson distribution is lower than that obtained with a Poisson distribution, assuming identical mean doses. A similar result holds for mixed Poisson distributions. Numerical examples indicate that the theoretical single-hit risk is fairly insensitive to moderate clustering, though the effect tends to be more pronounced for low mean doses. Furthermore, using Jensen's inequality, an upper bound on risk is derived that tends to better approximate the exact theoretical single-hit risk for highly overdispersed dose distributions. The bound holds with any dose distribution (characterized by its mean and zero inflation index) and any conditional dose response model that is concave in the dose variable. Its application is exemplified with published data from Norovirus feeding trials, for which some of the administered doses were prepared from an inoculum of aggregated viruses. The potential implications of clustering for dose-response assessment as well as practical risk characterization are discussed. PMID- 26812259 TI - Keeping It Local: Dispersal Limitations of Coral Larvae to the High Latitude Coral Reefs of the Houtman Abrolhos Islands. AB - In 2011 the first recorded bleaching event for the high latitude Houtman Abrolhos Islands (HAI) coral communities was documented. This bleaching event highlighted the question of whether a supply of 'heat tolerant' coral recruits from the tropical north would be sufficient to provide a level of resistance for these reefs to future warming events. Using Lagrangian modelling we showed that due to its regional isolation, large-scale larval input from potential tropical northern source populations to the HAI is unlikely, despite the southward flowing Leeuwin current. Successful recruitment to artificial substrates was recorded following the bleaching event. However, this was negligible (0.4 +/- 0.1 recruits per tile) compared to 2013 post impact recruitment (128.8 +/- 15.8 recruits per tile). Our data therefore provides preliminary evidence suggesting that the connectivity of the HAI with coral communities in the north is limited, and population maintenance and recovery is likely driven primarily by self-recruitment. Given the low thermal tolerance of the HAI coral communities, the dominance of Acropora, and the apparent reliance on self-recruitment, an increased frequency of thermally anomalous conditions at the HAI (such as experienced in 2011) has the potential to reduce the long-term stability of the HAI coral populations and species that depend upon them. PMID- 26812260 TI - AYAO: Looking Back at 2013 and Ahead to 2014 and One of the Next Developments in the Field of AYAO-SAYAO. PMID- 26812261 TI - Fifteen Years' Experience of the Brazilian Osteosarcoma Treatment Group (BOTG): A Contribution from an Emerging Country. AB - PURPOSE: Little information is available regarding the tumor features, prognostic factors, and treatment results in children and adolescents and young adults (AYAs) with osteosarcoma diagnosed in developing countries. We reviewed the results of three observational cohorts of osteosarcoma patients treated in an emerging country. METHODS: A total of 604 patients below the age of 30 years with high-grade osteosarcoma were prospectively enrolled in the Brazilian Osteosarcoma Treatment Group (BOTG) studies III, IV, and V. Gender, age, time from onset of symptoms to diagnosis, primary tumor site, presence or absence of metastases at diagnosis, tumor size, type of surgery (limb-sparing or amputation), treatment protocol, and histological response were correlated with survival. RESULTS: The estimated 5-year overall survival and event-free survival (EFS) rates for the 553 eligible patients were 49% and 39% respectively; of the 390 non-metastatic patients included in the total, overall- and event-free survival were 59% and 48% respectively. Metastases at diagnosis, primary tumor site, type of surgery, and histological response were significant predictors of overall survival and EFS in univariate and multivariate analysis, whereas tumor size and treatment protocol lost prognostic significance in multivariate analysis. CONCLUSION: We report on the outcome of three consecutive studies for the treatment of osteosarcoma carried out in Brazil over 15 years. Although the survival rates presented are below those reported in current literature, it represents the result of a favorable experience gathered from the national collaborative work. PMID- 26812262 TI - National Cancer Research Institute Teenage and Young Adult Clinical Studies Group: The United Kingdom Approach to Research. International Perspectives on AYAO, Part 4. AB - The unique psychosocial needs of teenagers and young adults (TYAs) with cancer have been recognized for some time in the United Kingdom. The non-profit Teenage Cancer Trust pioneered dedicated units for TYAs in 1990, and by 2005, the United Kingdom National Institute for Health and Clinical Excellence (NICE) issued healthcare policy advocating age-appropriate care. The National Cancer Research Institute Teenage and Young Adult Clinical Studies Group (NCRI TYA CSG) was also established in 2005. This national research group promotes and generates research specifically for TYAs with cancer, broadly those aged 13-24 years at diagnosis. The work of the TYA CSG to date has focused on six themes: (1) benchmarking clinical trial availability and access for TYAs; (2) developing links with other NCRI tumor-specific Clinical Studies Groups; (3) identifying priority areas for health services research; (4) evaluating the requirement for a cancer registry function for TYAs; (5) identifying issues for late effects and survivorship; and (6) identifying host- and tumor-specific biological differences in TYA cancer. Here we describe some of the research developments of the NCRI TYA CSG in the context of cancer research in the United Kingdom and healthcare policy for TYAs. PMID- 26812263 TI - Salivary Adenoid Cystic Carcinoma with Contralateral Cavernous Sinus Metastasis: A Rare Adult Tumor in an Adolescent Patient. AB - Adenoid cystic carcinoma (ACC) accounts for only 1% of all malignant head and neck tumors, and rarely affects children or adolescents. We present a 16-year-old female patient who was diagnosed with ACC at 12 years of age. The primary tumor was located in the left parotid gland. Initial treatment consisted of surgical resection and radiation therapy. Less than two years later, she developed recurrent disease in the right cavernous sinus with pulmonary metastases. At the time of this report, she is alive with disease. Both the patient's age and pattern of metastasis are rarely reported in the literature. PMID- 26812264 TI - Monolithically Integrated Metal/Semiconductor Tunnel Junction Nanowire Light Emitting Diodes. AB - We have demonstrated for the first time an n(++)-GaN/Al/p(++)-GaN backward diode, wherein an epitaxial Al layer serves as the tunnel junction. The resulting p contact free InGaN/GaN nanowire light-emitting diodes (LEDs) exhibited a low turn on voltage (~2.9 V), reduced resistance, and enhanced power, compared to nanowire LEDs without the use of Al tunnel junction or with the incorporation of an n(++) GaN/p(++)-GaN tunnel junction. This unique Al tunnel junction overcomes some of the critical issues related to conventional GaN-based tunnel junction designs, including stress relaxation, wide depletion region, and light absorption, and holds tremendous promise for realizing low-resistivity, high-brightness III nitride nanowire LEDs in the visible and deep ultraviolet spectral range. Moreover, the demonstration of monolithic integration of metal and semiconductor nanowire heterojunctions provides a seamless platform for realizing a broad range of multifunctional nanoscale electronic and photonic devices. PMID- 26812265 TI - The anti-dementia drug candidate, (-)-clausenamide, improves memory impairment through its multi-target effect. AB - Multi-target drugs, such as the cocktail therapy used for treating AIDS, often show stronger efficacy than single-target drugs in treating complicated diseases. This review will focus on clausenamide (clau), a small molecule compound originally isolated from the traditional Chinese herbal medicine, Clausenalansium. The finding of four chiral centers in clau molecules predicted the presence of 16 clau enantiomers, including (-)-clau and (+)-clau. All of the predicted enantiomers have been successfully synthesized via innovative chemical approaches, and pharmacological studies have demonstrated (-)-clau as a eutomer and (+)-clau as a distomer in improving cognitive function in both normal physiological and pathological conditions. Mechanistically, the nootropic effect of (-)-clau is mediated by its multi-target actions, which include mild elevation of intracellular Ca(2+) concentrations, modulation of the cholinergic system, regulation of synaptic plasticity, and activation of cellular and molecular signaling pathways involved in learning and memory. Furthermore, (-)-clau suppresses the pathogenesis of Alzheimer's disease by inhibiting multiple etiological processes: (1) beta amyloid protein-induced intracellular Ca(2+) overload and apoptosis and (2) tau hyperphosphorylation and neurodegeneration. In conclusion, the nature of the multi-target actions of (-)-clau substantiates it as a promising chiral drug candidate for enhancing human cognition in normal conditions and treating memory impairment in neurodegenerative diseases. PMID- 26812266 TI - A novel allele, HLA-B*15:259, was identified in a Taiwanese individual by sequence-based typing. AB - A one nucleotide replacement in codon 24 of HLA-B*15:54 results in a novel allele, HLA-B*15:259. PMID- 26812267 TI - Pulse-Reverse Electrodeposition and Micromachining of Graphene-Nickel Composite: An Efficient Strategy toward High-Performance Microsystem Application. AB - Graphene reinforced nickel (Ni) is an intriguing nanocomposite with tremendous potential for microelectromechanical system (MEMS) applications by remedying mechanical drawbacks of the metal matrix for device optimization, though very few related works have been reported. In this paper, we developed a pulse-reverse electrodeposition method for synthesizing graphene-Ni (G-Ni) composite microcomponents with high content and homogeneously dispersed graphene filler. While the Vickers hardness is largely enhanced by 2.7-fold after adding graphene, the Young's modulus of composite under dynamic condition shows ~1.4-fold increase based on the raised resonant frequency of a composite microcantilever array. For the first time, we also demonstrate the application of G-Ni composite in microsystems by fabricating a Si micromirror with the composite supporting beams as well as investigate the long-term stability of the mirror at resonant vibration. Compared with the pure Ni counterpart, the composite mirror shows an apparently lessened fluctuations of resonant frequency and scanning angle due to a suppressed plastic deformation even under the sustaining periodic loading. This can be ascribed to the reduced grain size of Ni matrix and dislocation hindering in the presence of graphene by taking into account the crystalline refinement strengthen mechanism. The rational discussions also imply that the strong interface and efficient load transfer between graphene layers and metal matrix play an important role for improving stiffness in composite. It is believed that a proper design of graphene-metal composite makes it a promising structural material candidate for advanced micromechanical devices. PMID- 26812268 TI - Challenges in Clinical Nurse Specialist Education and Practice. AB - Clinical nurse specialists (CNSs) are well-positioned to participate in the transformation of healthcare as outlined by the Institute of Medicine and called upon by the Patient Protection and Affordable Care Act of 2010. CNSs exercise their expertise through population-based care across three spheres of influence (patient/family, nurses/other professionals, systems). However, challenges during the educational process as well as implementation in practice can be barriers to optimization of the role, denying the public full benefit from the potential of CNSs. This article highlights some of the issues and provides solutions for mitigating these difficulties. PMID- 26812269 TI - Education and Practice Barriers for Certified Registered Nurse Anesthetists. AB - Of the recognized advanced practice registered nursing (APRN) specialties, Certified Registered Nurse Anesthetists (CRNAs) have historically experienced the most vigorous and organized resistance from outside entities regarding rights to practice to the full scope of their education and experience. Opposition to nurse anesthetists practicing to the full scope of their education and training is present in the clinical arena and educational milieu. PMID- 26812270 TI - Midwifery Practice and Education: Current Challenges and Opportunities. AB - Midwifery clinical practice and education has changed significantly since Mary Breckinridge first introduced nurse-midwives to the United States in 1925. This article discusses current challenges in midwifery clinical practice and education and proposes possible solutions. Midwifery clinical challenges include restrictive legislation and business-related barriers, including but not limited to physician supervision restrictions, prescriptive authority, out-of-hospital birth legislation, and third party reimbursement. Educational challenges highlighted include the current healthcare climate's influence on midwifery education, the contribution of clinical sites and preceptors, and the benefits of midwifery education. PMID- 26812271 TI - Addressing Issues Impacting Advanced Nursing Practice Worldwide. AB - Advanced practice nursing roles are developing globally, and opportunities for advanced practice nursing are expanding worldwide due to the need for expert nursing care at an advanced level of practice. Yet it is well recognized that barriers exist with respect to APRNs being able to practice to the full extent of their education and training. Addressing barriers to APRN practice worldwide and ensuring that APRNs are able to practice to the full extent of their education and training can help to promote optimal role fulfillment as well as assessment of the impact of the APRN role. PMID- 26812272 TI - Avoiding Negative Dysphagia Outcomes. AB - Dysphagia in adults affects their quality of life and can lead to life threatening conditions. The authors draw on both 30 years of experience as clinicians and also on expert testimony in adult, dysphagia-malpractice cases to make five recommendations with the aim of preventing dysphagia-related deaths. They discuss the importance of informed consent documents and suggest the following nursing actions to reduce these often unnecessary tragedies: consider the importance of diet status; understand and follow speech-language pathologists' recommendations; be familiar with the dysphagia assessment; be responsive to the need for an instrumental assessment; and ensure dysphagia communication is accurate and disseminated among healthcare professionals. They conclude that most negative dysphagia-management outcomes can be prevented and that nurses play a pivotal role in this prevention. PMID- 26812273 TI - Honduran Nurses' Work-Related Rewards and Challenges: Implications for International Service Learning and Collaboration. PMID- 26812274 TI - Informatics: Integrating a Geographic Information System into Nursing Research: Potentials and Challenges. PMID- 26812275 TI - Unusual Dermoscopic Patterns of Seborrheic Keratosis. AB - BACKGROUND: Seborrheic keratoses (SKs) may sometimes mimic benign and malignant skin tumors, and a biopsy can be necessary in order to rule out malignancy. METHODS: From the database of our pigmented lesion clinic, we evaluated the dermoscopic features of difficult-to-diagnose SKs that were biopsied between January 2010 and December 2014. RESULTS: SKs represented 3.8% of all excised lesions (161/ 4,182). Specifically, 91 (56.5%) were excised to rule out melanoma, 63 (39.1%) to rule out squamous cell carcinoma and 7 (4.4%) to rule out basal cell carcinoma. The following 10 global dermoscopic patterns were identified: multicomponent (32; 19.9%); reticular (24; 14.9%), characterized by an irregular pigment network; bowenoid (21; 13.0%); hairpin (19; 11.8%); keratoacanthoma-like (16; 9.9%); blue-nevus-like (15; 9.3%); lichenoid (6; 3.7%); hyperkeratotic (6; 3.7%); clonal (5; 3.1%); spitzoid (5; 3.1%). Furthermore, 12 SKs (7.5%) were not included in any of such patterns (not classified). CONCLUSION: Our results are in line with previous studies highlighting the dermoscopic variability of SKs. Although excised SKs may be classified into 1 of 10 repetitive dermoscopic patterns, a biopsy remains mandatory for those that cannot be clearly differentiated from common skin malignancies. PMID- 26812277 TI - Electron-Transfer Kinetics within Supramolecular Assemblies of Donor Tetrapyrrolytic Dyes and an Acceptor Palladium Cluster. AB - 9,18,27,36-Tetrakis[meso-(4-carboxyphenyl)]tetrabenzoporphyrinatozinc(II) (TCPBP, as a sodium salt) was prepared in order to compare its photoinduced electron transfer behavior toward unsaturated cluster Pd3(dppm)3(CO)(2+) ([Pd3(2+)]; dppm = Ph2PCH2PPh2 as a PF6(-) salt) with that of 5,10,15,20-tetrakis[meso-(4 carboxyphenyl)]porphyrinatozinc(II) (TCPP) in nonluminescent assemblies of the type dye...[Pd3(2+)]x (x = 0-4; dye = TCPP and TCPBP) using femtosecond transient absorption spectroscopy. Binding constants extracted from UV-vis titration methods are the same as those extracted from fluorescence quenching measurements (static model), and both indicate that the TCPBP...[Pd3(2+)]x assemblies (K14 = 36000 M(-1)) are slightly more stable than those for TCPP...[Pd3(2+)]x (K14 = 27000 M(-1)). Density functional theory computations (B3LYP) corroborate this finding because the average ionic Pd...O distance is shorter in the TCPBP...[Pd3(2+)] assembly compared to that for TCPP...[Pd3(2+)]. Despite the difference in the binding constants and excited-state driving forces for the photoinduced electron transfer in dye*...[Pd3(2+)] -> dye(*+)...[Pd3(*+)], the time scale for this process is ultrafast in both cases (<85 fs). The time scales for the back electron transfers (dye(*+)...[Pd3(*+)] -> dye...[Pd3(2+)]) occurring in the various observed species (dye...[Pd3(2+)]x; x = 0-4) are the same for both series of assemblies. It is concluded that the structural modification on going from porphyrin to tetrabenzoporphyrin does not greatly affect the kinetic behavior in these processes. PMID- 26812276 TI - Oxaspirol B with p97 Inhibitory Activity and Other Oxaspirols from Lecythophora sp. FL1375 and FL1031, Endolichenic Fungi Inhabiting Parmotrema tinctorum and Cladonia evansii. AB - A new metabolite, oxaspirol D (4), together with oxaspirols B (2) and C (3) were isolated from Lecythophora sp. FL1375, an endolichenic fungus isolated from Parmotrema tinctorum, whereas Lecythophora sp. FL1031 inhabiting the lichen Cladonia evansii afforded oxaspirols A (1), B (2), and C (3). Of these, oxaspirol B (2) showed moderate p97 ATPase inhibitory activity. A detailed characterization of all oxaspirols was undertaken because structures proposed for known oxaspirols have involved incomplete assignments of NMR spectroscopic data leading only to their planar structures. Thus, the naturally occurring isomeric mixture (2a and 2b) of oxaspirol B was separated as their diacetates (5a and 5b) and the structures and absolute configurations of 1, 2a, 2b, 3, and 4 were determined by the application of spectroscopic techniques including two-dimensional NMR and the modified Mosher's ester method. Oxaspirol B (2) and its diacetates 5a and 5b were evaluated for their ATPase inhibitory activities of p97, p97 mutants, and other ATP-utilizing enzymes, and only 2 was found to be active, indicating the requirement of some structural features in oxaspirols for their activity. Additional biochemical and cellular assays suggested that 2 was a reversible, non ATP competitive, and specific inhibitor of p97. PMID- 26812278 TI - How to think about your drink: Action-identification and the relation between mindfulness and dyscontrolled drinking. AB - Cross-sectional and intervention research have shown that mindfulness is inversely associated with difficulties in controlling alcohol use. However, little is known regarding the mechanisms through which mindfulness is related to increased control over drinking. One potential mechanism consists of the way individuals represent their drinking behaviour. Action identification theory proposes that self-control of behaviour is improved by shifting from high-level representations regarding the meaning of a behaviour to lower-level representations regarding "how-to" aspects of a behaviour. Because mindfulness involves present-moment awareness, it may help to facilitate such shifts. We hypothesized that an inverse relation between mindfulness and dyscontrolled drinking would be partially accounted for by the way individuals mentally represent their drinking behaviour - i.e., reduced levels of high-level action identification and increased levels of low-level action identification. One hundred and twenty five undergraduate psychology students completed self-report measures of mindful awareness, action identification of alcohol use, and difficulty in controlling alcohol use. Results supported the hypothesis that high level action identification partially mediates the relation between mindfulness and dyscontrolled drinking but did not support a mediating role for low-level action identification. These results suggest that mindfulness can improve self control of alcohol by changing the way we think about our drinking behaviour. PMID- 26812279 TI - Covalent Ras Dimerization on Membrane Surfaces through Photosensitized Oxidation. AB - Ras, a small GTPase found primarily on the inner leaflet of the plasma membrane, is an important signaling node and an attractive target for anticancer therapies. Lateral organization of Ras on cellular membranes has long been a subject of intense research; in particular, whether it forms dimers on membranes as part of its regulatory function has been a point of great interest. Here we report Ras dimer formation on membranes by Type II photosensitization reactions, in which molecular oxygen mediates the radicalization of proteins under typical fluorescence experimental conditions. The presence of Ras dimers on membranes was detected by diffusion-based fluorescence techniques including fluorescence correlation spectroscopy and single particle tracking, and molecular weights of the stable covalently coupled species were confirmed by gel electrophoresis. Fluorescence spectroscopy implicates interprotein dityrosine as one of the dimerization motifs. The specific surface tyrosine distribution on Ras renders the protein especially sensitive to this reaction, and point mutations affecting surface tyrosines are observed to alter dimerization potential. The photosensitization reactions are reflective of physiological oxidative stress induced by reactive oxygen species, suggesting such processes may occur naturally and influence signaling pathways in cells. PMID- 26812280 TI - Interaction between Methylation and CpG Single-Nucleotide Polymorphisms in the HTR2A Gene: Association Analysis with Suicide Attempt in Schizophrenia. AB - Dysfunctional mechanisms in the serotonergic system have been implicated in suicidal behavior among patients with schizophrenia. However, previous association analyses of major serotonin genes have provided inconsistent findings regarding their role in suicidal behavior. The goal of the current study was to identify single-nucleotide polymorphisms (SNP) within HTR2A that directly affect CpG methylation sites in schizophrenic patients with suicidal behavior. Furthermore, direct methylation analysis was performed using genomic DNA from peripheral leukocytes employing bisulfite pyrosequencing to assess the contributions of six CpG sites in HTR2A exon I in 67 schizophrenia patients assessed for lifetime suicide attempt. Potential methylation in 25 CpG SNPs across the entire HTR2A gene was analyzed considering their direct contribution to methylation. When we compared direct methylation between attempters and nonattempters, we found that only the polymorphic T102C (rs6313) was significantly different between the two groups (p = 0.02). Furthermore, in the potential methylation analysis, we found a nominal association with suicide attempt for six of the 25 SNPs analyzed, i.e. rs2770293 (p = 0.045), rs6313 (p = 0.033), rs17068986 (p = 0.029), rs4942578 (p = 0.024), rs1728872 (p = 0.014), and rs9534511 (p = 0.003). The results of this investigation provide preliminary evidence that the combined analysis of CpG SNPs and methylation may be useful for investigating the genetic and epigenetic factors involved in suicidal behavior. PMID- 26812282 TI - Detection of Influenza D Virus among Swine and Cattle, Italy. PMID- 26812281 TI - Diabetes is associated with cerebrovascular but not Alzheimer's disease neuropathology. AB - INTRODUCTION: The relationship of diabetes to specific neuropathologic causes of dementia is incompletely understood. METHODS: We used logistic regression to evaluate the association between diabetes and infarcts, Braak neurofibrillary tangle stage, and neuritic plaque score in 2365 autopsied persons. In a subset of >1300 persons with available cognitive data, we examined the association between diabetes and cognition using Poisson regression. RESULTS: Diabetes increased odds of brain infarcts (odds ratio [OR] = 1.57, P < .0001), specifically lacunes (OR = 1.71, P < .0001), but not Alzheimer's disease neuropathology. Diabetes plus infarcts was associated with lower cognitive scores at end of life than infarcts or diabetes alone, and diabetes plus high level of Alzheimer's neuropathologic changes was associated with lower mini-mental state examination scores than the pathology alone. DISCUSSION: This study supports the conclusions that diabetes increases the risk of cerebrovascular but not Alzheimer's disease pathology, and at least some of diabetes' relationship to cognitive impairment may be modified by neuropathology. PMID- 26812283 TI - Acute Colitis Caused by Helicobacter trogontum in Immunocompetent Patient. PMID- 26812284 TI - Silica encapsulated lipid-based drug delivery systems for reducing the fed/fasted variations of ziprasidone in vitro. AB - Ziprasidone is a poorly water-soluble antipsychotic drug that demonstrates low fasted state oral bioavailability and a clinically significant two-fold increase in absorption when dosed postprandially. Owing to significant compliance challenges faced by schizophrenic patients, a novel oral formulation of ziprasidone that demonstrates improved fasted state absorption and a reduced food effect is of major interest, and is therefore the aim of this research. Three lipid-based drug delivery systems (LBDDS) were developed and investigated: (a) a self-nanoemulsifying drug delivery system (SNEDDS), (b) a solid SNEDDS formulation, and (c) silica-lipid hybrid (SLH) microparticles. SNEDDS was developed using Capmul MCM(r) and Tween 80(r), and solid SNEDDS was fabricated by spray-drying SNEDDS with Aerosil 380(r) silica nanoparticles as the solid carrier. SLH microparticles were prepared in a similar manner to solid SNEDDS using a precursor lipid emulsion composed of Capmul MCM(r) and soybean lecithin. The performance of the developed formulations was evaluated under simulated digesting conditions using an in vitro lipolysis model, and pure (unformulated) ziprasidone was used as a control. While pure ziprasidone exhibited the lowest rate and extent of drug solubilization under fasting conditions and a significant 2.4-fold increase in drug solubilization under fed conditions, all three LBDDS significantly enhanced the extent of drug solubilization under fasting conditions between 18- and 43-folds in comparison to pure drug. No significant difference in drug solubilization for the fed and fasted states was observed for the three LBDDS systems. To highlight the potential of LBDDS, mechanism(s) of action and various performance characteristics are discussed. Importantly, LBDDS are identified as an appropriate formulation strategy to explore further for the improved oral delivery of ziprasidone. PMID- 26812286 TI - Bioinformatics analyses combined microarray identify the differentially expressed microRNAs in periventricular leukomalacia. AB - OBJECTIVES: With the improvement of premature infant cure rate and livability, the incidence of PVL has been one of the main reasons for premature infant nervous system sequelae. miRNAs are important in the regulation of cell growth, differentiation, apoptosis and carcinogenesis. The aim of the present study was to identify differentially expressed miRNAs between PVL and normal tissues. METHODS: The target genes of significant miRNA were retrieved from the miRecords database. Furthermore, GO analysis and biological process interaction network was constructed using the BiNGO and Cytoscape software. Finally, KEGG analysis from DAVID was used to find meaningful signaling pathway. RESULTS: In conclusion, this study identified 16 differentially expressed miRNAs, which may be important in the progression of PVL and miRNA 141 demonstrated the greatest quantity of target genes. In addition, Hdac4, Lamc1, Irs1 and Zeb1 are the most frequently appeared ones among proved genes. Wnt signaling pathway and Neurotrophin signaling pathway were identified to be significantly associated with PVL. CONCLUSION: This work may bring some new hints for the pathogenesis of PVL in the future work. However, further investigation regarding the specific function is required. PMID- 26812285 TI - Expression of the Retrotransposon Helena Reveals a Complex Pattern of TE Deregulation in Drosophila Hybrids. AB - Transposable elements (TEs), repeated mobile sequences, are ubiquitous in the eukaryotic kingdom. Their mobilizing capacity confers on them a high mutagenic potential, which must be strongly regulated to guarantee genome stability. In the Drosophila germline, a small RNA-mediated silencing system, the piRNA (Piwi interacting RNA) pathway, is the main responsible TE regulating mechanism, but some stressful conditions can destabilize it. For instance, during interspecific hybridization, genomic stress caused by the shock of two different genomes can lead, in both animals and plants, to higher transposition rates. A recent study in D. buzatii-D. koepferae hybrids detected mobilization of 28 TEs, yet little is known about the molecular mechanisms explaining this transposition release. We have characterized one of the mobilized TEs, the retrotransposon Helena, and used quantitative expression to assess whether its high transposition rates in hybrids are preceded by increased expression. We have also localized Helena expression in the gonads to see if cellular expression patterns have changed in the hybrids. To give more insight into changes in TE regulation in hybrids, we analysed Helena specific piRNA populations of hybrids and parental species. Helena expression is not globally altered in somatic tissues, but male and female gonads have different patterns of deregulation. In testes, Helena is repressed in F1, increasing then its expression up to parental values. This is linked with a mislocation of Helena transcripts along with an increase of their specific piRNA levels. Ovaries have additive levels of Helena expression, but the ping-pong cycle efficiency seems to be reduced in F1 hybrids. This could be at the origin of new Helena insertions in hybrids, which would be transmitted to F1 hybrid female progeny. PMID- 26812287 TI - Cerebral blood flow in transient hypothyroidism after thyroidectomy: Arterial spin labeling magnetic resonance study. AB - OBJECTIVE: Our purpose was to apply arterial spin labeling (ASL) magnetic resonance imaging (MRI) to characterize regional cerebral blood flow (rCBF: the CBF values at each voxel / the subject's mean global flow) in patients with transient hypothyroidism after thyroidectomy. METHODS: Our study included 27 patients who had undergone total thyroidectomy due to thyroid cancer and pre-131I therapy and 24 controls. Patients were evaluated at two points in time: before and after thyroxine replacement. The assessments for the patients and controls consisted of evaluation of ASL of the brain and the severity of depression using 21-question Beck Depression Inventory (BDI). The assessments for the patients also included thyroid hormone lebel. We performed the comparison of rCBF between patients and controls, and investigated the association between rCBF in hypothyroid patients and thyroid hormone level and BDI score. RESULTS: Hypothyroid patients showed a significantly lower rCBF in the cerebellum, the left thalamus and some regions, and showed a significantly higher rCBF in the bilateral frontal gyri and some regions. After thyroxine replacement, patients showed a significantly lower rCBF mostly in the right frontal lobe, and showed a significantly higher rCBF in the left frontal and parietal lobes, although the degree of rCBF changes was lower after thyroxine replacement. In the hypothyroid patients, significant positive relationships were found between free T3 and the rCBF (p<0.05 corrected for FDR). CONCLUSIONS: This study revealed alterations of rCBF in patients with transient hypothyroidism. ASL is helpful for understanding of the effects of hypothyroidism on the brain. PMID- 26812288 TI - Cerebral salt wasting in pediatric critical care; not just a neurosurgical disorder anymore. AB - OBJECTIVE: Cerebral salt-wasting syndrome (CSWS) is a hypovolemic hyponatremia caused by natriuresis and diuresis, of which the exact pathogenesis is unknown. Although CSWS has been more commonly described to be associated with neurosurgical disorders, increasing numbers of patients are diagnosed and new etiological factors are being identified as the awareness of it increases. METHODS: The files of the patients who had been hospitalized and treated with the diagnosis of CSWS at the pediatric critical care unit during the last three years were retrospectively reviewed. RESULTS: Totally 9 patients had been treated with the diagnosis of CSWS. The causes of CSWS were identified as tuberculosis meningitis in two patients, status epilepticus in two patients, ketamine infusion in one patient, medulloblastoma in one patient, sepsis in one patient, brain oedema following child abuse in one patient, and cerebral infarct in one patient. All of the patients had received isotonic saline and hypertonic saline while 77.7% of them had received fludrocortisone. The mean time to correction of hyponatremia was 20.37+/-14.73 days. One patient had died. CONCLUSION: Cerebral salt-wasting syndrome is increasingly described in the etiology of hyponatremia that is commonly seen in children hospitalized especially at critical care units. Serum sodium, urinary sodium and polyuria should be primarily considered in the diagnosis, and supportive laboratory tests such as uric acid and brain natriuretic peptide (BNP) should not be stipulated. At hospitals providing inpatient care services, clinical and laboratory characteristics of CSWS should be known in detail especially at pediatric critical care units. PMID- 26812289 TI - Genetic polymorphisms by deletion in genes that encode for glutathione S transferases are associated with nicotine dependence and tobacco use-related medical disorders. AB - OBJECTIVE: We examine the relationship between nicotine dependence (ND) and ND related medical disease and polymorphisms by deletion in genes that encode glutathione S-transferases (GSTs), e.g. GSTM1 and GSTT1. Individuals with homozygous gene deletions show deficiencies in GSTs enzyme activities impairing detoxification. METHODS: This study comprised 182 tobacco users and 182 controls (neversmokers). GSTM1 and GSTT1 polymorphisms were assessed using a Multiplex- PCR based protocol. RESULTS: Logistic regression analyses showed a significant association between ND and the GSTM1 and GSTT1 null genotypes. There were no significant associations between GSTT1, GSTM1 and GSTT1/M1 genetic variants and the Fagerstrom test for ND, age at onset, smoking cessation or a family history of ND. Patients with ND had increased rates of a family ND history and an increased prevalence of cardiovascular disease, hypertension, and lung disease. The null genotypes were associated with hypertension (i.e. GSTT1 * ND interaction), diabetes type 2 (i.e. GSTM1 * GSTT1 interaction), lung disease (i.e. GSTM1 * ND interaction) and cancer (i.e. GSTT1). The results show that GST null genotypes may confer protection against ND while they increase risk towards ND-related medical disorders. PMID- 26812290 TI - Higher lipid peroxidation in former-smokers vs. never-smokers - study in postmenopausal women. AB - OBJECTIVES: One of the most spectacular exogenous prooxidative agents is cigarette smoking, constituting a well documented risk factor for several diseases. In turn it is suggested that hormone replacement therapy (HRT) in postmenopausal women can contribute to oxidative status. The aim of the study was to evaluate the level of oxidative damage to membrane lipids in blood serum collected from never-smokers and former-smokers. The study was performed in postmenopausal women, who were or were not HRT users. METHODS: Ninety (90) female volunteers, aged from 46 to 67 years, were enrolled. Two major groups were considered, i.e. never-smokers (n=44) and formersmokers (n=46), which were additionally subgrouped to HRT users (HRT+) and HRT non-users (HRT-). Anthropometric parameters related to obesity were also calculated. The main groups were well matched at baseline in terms of age. The level of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA), as the index of LPO, was measured spectrophotometrically. RESULTS: The level of LPO was higher in former-smokers than in never-smokers, regardless of HRT use. The level of LPO did constitute the only independent factor associated with past smoking in the entire examined group, as well as after stratification to HRT users and HRT non-users. LPO level was not associated with HRT treatment. No positive correlations were found between LPO level and anthropometric parameters. CONCLUSION: Past smoking is independently associated with the increased damage to membrane lipids regardless of the use of HRT in postmenopausal women. Smoking cessation is not always associated with complete reversion of excessive oxidative damage to all biological macromolecules. PMID- 26812291 TI - Justice in psychotherapy. AB - Justice is one of the fundamental concepts of right ordering of human relationships. Justice is a regulative idea for the arrangement of society preceding the law and already seen in animals; the sense of justice is observed as early as in young children. The ability to altruistic behavior, sense of fairness, reciprocity and mutual help are probably genetically determined as a disposition, which may further develop or be deformed by education. Although justice issues are common in psychotherapy, they may not be reflected and processed in the course of therapy. In psychotherapy, justice issues appear directly in what the client says (mostly about injustice), but more frequently the issues are implicitly contained in complaints and stories against a background of conflicts and problems. They may be related to the client's story, his or her problems with other people, and the therapeutic process itself, including client's selection of therapy, therapeutic relationship, and therapeutic change strategies. By increasing receptiveness to the issue of justice, the therapist may help improve the therapeutic process. Problems with justice between the therapist and the client may be revealed by honest therapist self-reflection or high-quality supervision. PMID- 26812292 TI - Mothers' dilemma - conducting delivery on the limits of the foetus viability. Case Report. AB - Ethical questions concerning problems of conducting delivery of enormously immature foetuses are subjected to intensive discussion and call for a permanent and wide consideration with the participation of all specialists, who are involved in the problem. The discussions have persisted over tens of years and became intensive particularly at the moment of defining the foetus viability. In the present contribution, the author illustrates the discussion by two selected case reports exemplifying the practical impact of conducting deliveries of enormously immature foetuses on the physician and particularly on the family. PMID- 26812293 TI - Polish experiences with paternal lymphocyte immunization in women with recurrent miscarriages. AB - OBJECTIVE: This study aimed to evaluate the efficacy of PLI and results of subsequent pregnancy in women with RM showing alloimmune response. MATERIALS AND METHODS: Immunological investigations were performed in patients with RM. Subsequently, PLI was administered to 241 patients at their request. Of these, 202 conceived between September 2005 and September 2012. RESULTS: Of the 202 women, 169 pregnancies resulted in term delivery; the remaining 33 resulted in subsequent miscarriages (success rate = 83.7%). During seven-years observations of 202 tested individuals, 114 women were pregnant again for the second time and 92 pregnancies of them resulted in the next term delivery (success rate =80.7%). CONCLUSIONS: Alloimmune background indicated that PLI might improve pregnancy outcome in patients suffering from RM. Long-term monitoring did not reveal any negative effects of PLI on the immunological system in the treated women or newborn babies. PMID- 26812294 TI - Prenatal diagnosis of cardiac rhabdomyoma associated with tuberous sclerosis: report of 3 cases. AB - Cardiac rhabdomyoma is the most common cardiac tumor in fetal life, accounting for 60-86% of primary fetal cardiac tumors. It is primarily benign, originating form myocardial muscles and consisting of immature myocytes. About 50-60% of these tumors are associated with tuberous sclerosis. In this report, we present the clinical course and discuss the importance of prenatal diagnosis of cardiac tumors and their follow-up after birth. PMID- 26812295 TI - Prolactin receptor mRNA expression in experimental diabetic nephropathy: Relationship with urinary albumin excretion. AB - OBJECTIVES: Disturbances of prolactin secretion, peptide hormone produced by the pituitary gland, occur in both the chronic renal failure and in diabetes mellitus. So far, the role that prolactin play in the pathology of diabetic nephropathy progression is still unclear. Therefore, the present study was intended to examine whether the renal mRNA expression of prolactin receptor (PRL R) is altered in experimental diabetes, and how such changes related to the development of albuminuria. METHODS: Adult female wistar rats were divided into two groups (n=6/group): control (non-diabetic) and diabetic. Diabetes was induced by a single dose injection of 55 mg/ kg streptozotocin. After ten weeks, renal mRNA expressions of both short and long forms of PRL-R were evaluated by real time polymerase chain reaction. RESULTS: Diabetes was associated with increases in urine albumin excretion (UAE), kidney weight/body weight ratio, serum prolactin and the mRNA expression of both long and short forms of PRL-R. Furthermore, UAE was significantly and positively correlated with serum prolactin levels and with mRNA expressions of both short and long forms of PRL-R. CONCLUSION: These results provide evidence, for the first time, that the development of experimental diabetic kidney disease is associated with increases in the renal expression of PRL-R, suggesting a potential role for prolactin in the development and progression of renal injury secondary to diabetes mellitus. PMID- 26812296 TI - Serum alpha-klotho concentrations in girls with anorexia nervosa. AB - BACKGROUND: Soluble alpha-klotho may influence energy homeostasis. It also plays a role in calcium-phosphate and vitamin D3 metabolism regulation. Two so far published studies have demonstrated that serum alpha-klotho levels in patients with AN are decreased, but their relationships with BMI and metabolic disturbances in these patients remain unclear. OBJECTIVES: The aim of the study was to assess the association between serum soluble alpha-klotho levels and glucose, calcium-phosphorus and vitamin D3 metabolism in girls with acute AN. METHODS: Serum soluble alpha-klotho concentrations were evaluated using commercially available ELISA kit in 31 Polish girls with restrictive AN and 29 healthy controls (C). Moreover, anthropometric measurements (weight, height, BMI) and laboratory assays (serum fasting glucose, insulin, HOMA-IR, total calcium, phosphorus as well as 25-hydroxy vitamin D3 and calcitriol) were performed. RESULTS: The mean serum alpha-klotho concentrations in the AN group were significantly lower than in the C group even after adjustment for BMI. Significant correlations between serum alpha-klotho and body mass (r=0.54; p=0.009), BMI (r=0.48; p=0.02), serum calcitriol (r=0.48; p=0.03), insulin (r=0.49; p=0.008) and HOMA-IR (r=0.54; p=0.006) were observed in the AN, but not in healthy controls. CONCLUSIONS: Serum alpha-klotho concentrations in female adolescents with AN are decreased in comparison with normal weight girls and strongly associated with their nutritional status, insulin sensitivity and active vitamin D3 levels. PMID- 26812297 TI - Sunitinib treatment for multifocal renal cell carcinoma (RCC) and pancreatic neuroendocrine tumor (NET) in patient with Von Hippel-Lindau disease. Case Report. AB - OBJECTIVE: Von Hippel-Lindau disease (VHL) is an autosomal, dominant, hereditary disease occurring in approximately one in 36,000 births. VHL disease produces a variety of tumors and cysts in the central nervous system and visceral organs. Surgical management, when possible, improves prognosis and extends patient's life. When surgery is impossible, treatment with tyrosine kinase inhibitors demonstrates encouraging response rates. MATERIAL AND METHOD: We present a 60 year old patient with coexistence of multifocal renal cell carcinomas (RCC) and pancreatic neuroendocrine tumor (NET) in VHL disease, who received Sunitinib as the best option of treatment. RESULTS: Progression - free survival time is over 4 years. Regarding her acceptable tolerance for tyrosine kinase inhibitors, medical treatment is continued. CONCLUSION: RCC and pancreatic NET associated with VHL are responsive to Sunitinib for prolonged periods of time. Tyrosine kinase inhibitors treatment for patients with multiple neoplasms associated with VHL disease may too be considered. Sunitinib showed acceptable toxicity. PMID- 26812298 TI - The association between metabolic complications and arterial hypertension in obese adolescents. AB - OBJECTIVE: There is increasing evidence for the contribution of obesity and its metabolic sequels in the development of arterial hypertension (AH). METHODS: The casual blood pressure (CBP), 24hABPM, ambulatory arterial stiffness index (AASI) and symmetric (sAASI) ambulatory arterial stiffness index (both derived from a 24 h ABPM) and selected laboratory tests were performed in 130 obese (mean BMI SDS 4.2) adolescents at the mean age of 13.7 years. RESULTS: AH was diagnosed in 36.2%, and in 33.8% patients on the basis of CBP and 24hABPM respectively. There were significant correlations between: CBPSBP insulin level (fasting r=0.19, p=0.03 and post glucose load r=0.18, p=0.04), HOMA-IR (r=0.18, p=0.04), and uric acid (UA) level (r=0.35, p<0.001); CBPDBP and UA level (r=0.23, p=0.01). There were significant correlations between 24hABPM parameters and cortisol secretion: dSBP and urinary free cortisol (r=0.3, p=0.03), nDBP and nMAP and cortisol rhythm (r=0.21, p=0.03). There a correlation between sAASI and creatinine level (r=0.29, p=0.002) and negative correlation between AASI and eGFR (r=-0.23, p=0.009). CONCLUSIONS: The increase of the CBP parameters is associated with insulin resistance and hyperuricemia, while the increase of ABPM results is proportional to the cortisol secretion in obese adolescents. PMID- 26812299 TI - The comparison of selected cerebrospinal fluid and serum cytokine levels in patients with multiple sclerosis and normal pressure hydrocephalus. AB - OBJECTIVES: Cytokine production and immune activation are associated with various pathological conditions including neurodegenerative disorders. One of them is multiple sclerosis (MS), known autoimmune disease. Inflammatory changes were also reported in normal pressure hydrocephalus (NPH), neurodegenerative disorder, which pathophysiology remains still unclear. The aim of this research was to compare the group of MS subjects with NPH patients and controls and to evaluate the potential inflammatory substance of NPH in comparison with autoimmune inflamed MS. METHODS: The levels of IL-1beta, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, INF-gamma, sCD40L and TNF-alpha were measured in cerebrospinal fluid (CSF) and plasma in subjects with MS (n=15), NPH (n=18) and controls (n=11) by multiplex assay. RESULTS: The increased levels of IL-1beta, IL-6, IL-10, IL-21 and TNF-alpha in cerebrospinal fluid of NPH subjects in comparison with MS patients and controls were found. Regarding the MS patients, we have confirmed increased IL-33 levels in cerebrospinal fluid and periphery as well as the increase of IL-1beta and IL-10 in cerebrospinal fluid and IL-4 and sCD40L in plasma. CONCLUSION: The enlarged brain ventricles in NPH may repress and activate brain structures to the production of IL-1beta, IL-6, IL 10, IL-21 and TNF-alpha, reflecting the inflammatory basis in NPH affected brain. The elevation of the above mentioned cytokines in MS was confirmed. PMID- 26812300 TI - Structural analysis of the alpha subunit of Na(+)/K(+) ATPase genes in invertebrates. AB - The Na(+)/K(+) ATPase is a ubiquitous pump coordinating the transport of Na(+) and K(+) across the membrane of cells and its role is fundamental to cellular functions. It is heteromer in eukaryotes including two or three subunits (alpha, beta and gamma which is specific to the vertebrates). The catalytic functions of the enzyme have been attributed to the alpha subunit. Several complete alpha protein sequences are available, but only few gene structures were characterized. We identified the genomic sequences coding the alpha-subunit of the Na(+)/K(+) ATPase, from the whole-genome shotgun contigs (WGS), NCBI Genomes (chromosome), Genomic Survey Sequences (GSS) and High Throughput Genomic Sequences (HTGS) databases across distinct phyla. One copy of the alpha subunit gene was found in Annelida, Arthropoda, Cnidaria, Echinodermata, Hemichordata, Mollusca, Placozoa, Porifera, Platyhelminthes, Urochordata, but the nematodes seem to possess 2 to 4 copies. The number of introns varied from 0 (Platyhelminthes) to 26 (Porifera); and their localization and length are also highly variable. Molecular phylogenies (Maximum Likelihood and Maximum Parsimony methods) showed some clusters constituted by (Chordata/(Echinodermata/Hemichordata)) or (Plathelminthes/(Annelida/Mollusca)) and a basal position for Porifera. These structural analyses increase our knowledge about the evolutionary events of the alpha subunit genes in the invertebrates. PMID- 26812301 TI - Reproducibility of Multiparametric Magnetic Resonance Imaging and Fusion Guided Prostate Biopsy: Multi-Institutional External Validation by a Propensity Score Matched Cohort. AB - PURPOSE: As the adoption of magnetic resonance imaging/ultrasound fusion guided biopsy expands, the reproducibility of outcomes at expert centers becomes essential. We sought to validate the comprehensive NCI (National Cancer Institute) experience with multiparametric magnetic resonance imaging and fusion guided biopsy in an external, independent, matched cohort of patients. MATERIALS AND METHODS: We compared 620 patients enrolled in a prospective trial comparing systematic biopsy to fusion guided biopsy at NCI to 310 who underwent a similar procedure at Long Island Jewish Medical Center. The propensity score, defined as the probability of being treated outside NCI, was calculated using the estimated logistic regression model. Patients from the hospital were matched 1:1 for age, prostate specific antigen, magnetic resonance imaging suspicion score and prior negative biopsies. Clinically significant disease was defined as Gleason 3 + 4 or greater. RESULTS: Before matching we found differences between the cohorts in age, magnetic resonance imaging suspicion score (each p <0.001), the number of patients with prior negative biopsies (p = 0.01), and the overall cancer detection rate and the cancer detection rate by fusion guided biopsy (each p <0.001). No difference was found in the rates of upgrading by fusion guided biopsy (p = 0.28) or upgrading to clinically significant disease (p = 0.95). A statistically significant difference remained in the overall cancer detection rate and the rate by fusion guided biopsy after matching. On subgroup analysis we found a difference in the overall cancer detection rate and the rate by fusion guided biopsy (p <0.001 and 0.003) in patients with prior negative systematic biopsy but no difference in the 2 rates (p = 0.39 and 0.51, respectively) in biopsy naive patients. CONCLUSIONS: Improved detection of clinically significant cancer by magnetic resonance imaging and fusion guided biopsy is reproducible by an experienced multidisciplinary team consisting of dedicated radiologists and urologists. PMID- 26812302 TI - Sac-1004, a Pseudo-Sugar Derivative of Cholesterol, Restores Erectile Function through Reconstruction of Nonleaky and Functional Cavernous Angiogenesis in the Streptozotocin Induced Diabetic Mouse. AB - PURPOSE: We examined whether and how Sac-1004, a vascular leakage blocker, would restore erectile function in an animal model of diabetic erectile dysfunction. MATERIALS AND METHODS: Eight-week-old C57BL/6J mice were used. Diabetes was induced by intraperitoneal injection of streptozotocin. Eight weeks after diabetes induction the animals were divided into 6 groups, including controls, diabetic mice that received repeat intracavernous injections of phosphate buffered saline (20 MUl) on days -3 and 0, and diabetic mice that received repeat intracavernous injections of Sac-1004 on days -3 and 0 (1, 2, 5 and 10 MUg, respectively, in 20 MUl phosphate buffered saline). One week after injection erectile function was measured by cavernous nerve stimulation. The penis was then harvested for histological examinations and Western blot analysis. RESULTS: Local delivery of Sac-1004 in the corpus cavernosum restored erectile function in diabetic mice. The highest erectile response was noted at a dose of 5 MUg with a response comparable to that in the control group. Sac-1004 significantly increased cavernous endothelial and smooth muscle contents, and induced endothelial nitric oxide synthase phosphorylation (Ser1177). Sac-1004 decreased extravasation of oxidized low density lipoprotein by restoring endothelial cell cell junction proteins and pericyte content. Sac-1004 also promoted tube formation in primary cultured mouse cavernous endothelial cells in vitro. Sac 1004 mediated cavernous angiogenesis and erectile function recovery was abolished by inhibiting angiopoietin-1-Tie2 signaling with soluble Tie2 antibody. CONCLUSIONS: With the effects of angiogenesis and antipermeability Sac-1004 reestablishes structural and functional cavernous sinusoids. This is highly promising for future treatment of erectile dysfunction from vascular causes. PMID- 26812303 TI - In Silico Screening and Molecular Dynamic Study of Nonsynonymous Single Nucleotide Polymorphisms Associated with Kidney Stones in the SLC26A6 Gene. AB - PURPOSE: SLC26A6 is a multifunctional anion transporter with a critical physiological role in the transport of oxalate anions. Recognizing a genetic variant of SLC26A6 would advance our understanding of oxalate transport in the formation of calcium oxalate stones. MATERIALS AND METHODS: All nsSNPs (nonsynonymous single nucleotide polymorphisms) reported in human SLC26A6 were investigated using 4 in silico tools, including SIFT (Sorting Intolerant From Tolerant), PROVEAN (Protein Variation Effect Analyzer), PhD-SNP (Predictor of human Deleterious Single Nucleotide Polymorphisms) and MutPred. A total of 426 subjects, including 225 with kidney stones and 201 healthy controls, were included in study to genotype the candidate disease associated nsSNP using allele specific polymerase chain reaction. Furthermore, the structural consequences due to the mutation were assessed using homology modeling and molecular dynamics simulation methods. RESULTS: The nsSNP rs184187143 was identified as a more probable disease associated variant in the SLC26A6 gene by in silico screening. The C allele carrier showed a 6.1-fold increased kidney stone risk compared with G allele carriers in the nsSNP (OR 6.1, 95% CI 1.36-27.38, p = 0.007). We found that the mutation from arginine to glycine leads to the loss of 2 hydrogen bonds and to an unstable structure in the STAS domain of SLC26A6. CONCLUSIONS: Our results indicate that the variant G539R in the SLC26A6 gene is associated with kidney stone risk, providing a clear clue to further achieve insight into oxalate transport in kidney stone formation. PMID- 26812304 TI - Effect of Stress Urinary Incontinence on the Sexual Function of Couples and the Quality of Life of Patients. AB - PURPOSE: Studies of the effects of stress urinary incontinence on the sexual function of couples are scarce. We prospectively evaluated couple sexual function and the relationship between sexual function and quality of life. We also compared quality of life in females with vs without stress urinary incontinence. MATERIALS AND METHODS: Sexually active females at least 21 years old with or without stress urinary incontinence and their partners were recruited for study. To assess sexual function the couples completed GRISS (Golombok Rust Inventory of Sexual Satisfaction) and a 1-item question on overall sexual experience, "Over the past 4 weeks, how satisfied have you been with your overall sexual life?" Additionally, females completed ICIQ-LUTSqol (International Consultation on Incontinence Questionnaire-Lower Urinary Tract Symptoms Quality of Life) to assess quality of life. RESULTS: For sexual function assessment 66 of 134 couples with (49.3%) and 95 of 176 without (54.0%) stress urinary incontinence were recruited. Females with stress urinary incontinence had lower overall sexual function, lower frequency of sexual intercourse, less satisfaction (each p <0.001) and higher avoidance behavior (p = 0.026). Partners of females with stress urinary incontinence had more problems with erectile dysfunction (p = 0.027), less satisfaction (p = 0.006) and lower frequency of sexual intercourse (p = 0.001) but no difference in overall GRISS score (p = 0.093). Couples with stress urinary incontinence had poorer overall sexual experience (p <0.05). Females with stress urinary incontinence had poorer quality of life than those without stress urinary incontinence (120 of 134, response rate 89.6% vs 145 of 176, response rate 82.4%, p <0.001). Sexual function and quality of life did not significantly correlate (r = 0.001, p = 0.997). CONCLUSIONS: Stress urinary incontinence in females is negatively associated not only with female quality of life and sexual function but also with partner sexual function. PMID- 26812306 TI - Heterosis and direct effects for Charolais-sired calf weight and growth, cow weight and weight change, and ratios of cow and calf weights and weight changes across warm season lactation in Romosinuano, Angus, and F cows in Arkansas. AB - The use of Brahman in cow-calf production offers some adaptation to the harsh characteristics of endophyte-infected tall fescue. Criollo breeds, such as the Romosinuano, may have similar adaptation. The objectives were to estimate genetic effects in Romosinuano, Angus, and crossbred cows for their weights, weights of their calves, and ratios (calf weight:cow weight and cow weight change:calf weight gain) across lactation and to assess the influence of forage on traits and estimates. Cows ( = 91) were bred to Charolais bulls after their second parity. Calves ( = 214) were born from 2006 to 2009. Cows and calves were weighed in early (April and June), mid- (July), and late lactation (August and October). Animal was a random effect in analyses of calf data; sire was random in analyses of cow records and ratios. Fixed effects investigated included calf age, calf sex, cow age-year combinations, sire breed of cow, dam breed of cow, and interactions. Subsequent analyses evaluated the effect of forage grazed: endophyte-free or endophyte-infected tall fescue. Estimates of maternal heterosis for calf weight ranged from 9.3 +/- 4.3 to 15.4 +/- 5.7 kg from mid-lactation through weaning ( < 0.05). Romosinuano direct effects (of the cow) were -6.8 +/- 3.0 and -8.9 +/- 4.2 kg for weights recorded in April and June. Calf weights and weight gains from birth were greater ( < 0.05) for calves of cows grazing endophyte-free tall fescue except in mid-summer. Cow weight change from April to each time was negative for Angus cows and lower ( < 0.05) than other groups. Cows grazing endophyte-free tall fescue were heavier ( < 0.05) at all times but had more weight loss in late lactation. Angus cows had the lowest ( < 0.05) ratios (negative) of cow weight change:calf weight gain, indicating an energy-deficit condition. Cows grazing endophyte-free tall fescue had more negative ( < 0.05) values for this trait but not in early lactation ( < 0.05). Estimates of heterosis ranged from 12.8 +/- 9.5 to 28.6 +/- 9.4 kg for cow weight, 7.9 +/- 3.0 to 15.8 +/- 5.0 kg for cow weight change, and 0.07 +/- 0.03 to 0.27 +/- 0.1 for cow weight change:calf weight gain. Direct Romosinuano effects ranged from 14.8 +/- 4.2 to 49.8 +/- 7.7 kg for cow weight change and 0.2 +/- 0.04 to 0.51 +/- 0.14 for cow weight change:calf weight gain. The adaptive ability of Romosinuano in temperate fescue regions may be favorable with respect to relative cow and calf weight but may be a consequence of lower milk-producing ability. PMID- 26812305 TI - Association of Itraconazole, a Hedgehog Inhibitor, and Bladder Cancer. AB - PURPOSE: Activation of Hedgehog (Hh) signaling has been implicated in early stages of bladder cancer development while loss of Hh signaling has been described during progression to more invasive disease. Itraconazole, an antifungal, is the only azole known to be a potent Hh pathway antagonist. We evaluated whether itraconazole use is associated with bladder cancer risk or progression. MATERIALS AND METHODS: We performed a case-control study nested in a United Kingdom database in 13,440 bladder cancer cases and 52,421 matched controls between 1995 and 2013. The use of itraconazole and other azoles was measured as the number of prescriptions. Conditional logistic regression was used for estimated AORs and the 95% CI of the association of bladder cancer with ever use and an increasing number of itraconazole prescriptions. Logistic regression was done to determine whether itraconazole use in patients diagnosed with bladder cancer was associated with invasive bladder cancer requiring cystectomy relative to the use of other azoles. RESULTS: Itraconazole was not associated with the risk of bladder cancer relative to never use (ever use AOR 0.89, 95% CI 0.70-1.14 and 4 or more prescriptions AOR 0.87, 95% CI 0.42-1.81). However, among patients diagnosed with bladder cancer there was a significantly increased risk of bladder cancer requiring cystectomy with itraconazole use (ever use AOR 2.05, 95% CI 1.12 3.38 and 2 or more prescriptions AOR 2.30, 95% CI 1.12-4.72). CONCLUSIONS: Inhibition of the Hh pathway with itraconazole was not associated with a risk of bladder cancer overall but it was associated with a higher risk of invasive bladder cancer requiring cystectomy. These data provide clinical evidence supporting the role of Hh signaling in regulating bladder cancer progression. PMID- 26812307 TI - Genetic parameters of objectionable fibers and of their associations with fleece traits in Corriedale sheep. AB - The aim of this research was to assess the variability and genetic relationships among binary traits denoting the presence or absence of objectionable fibers, namely pigmented (BINPPF), medullated (BINPMED), and kemp fibers (BINPK), and of fleece traits (fiber diameter [FD] and clean fleece weight [CFW]) in Corriedale sheep. Additionally, the total response to selection against objectionable fibers and indirect responses when selecting for fleece traits were evaluated. Fiber records from 679 animals and fleece records from 795 animals obtained from 2 experimental flocks (from 2005 to 2007) were used; the pedigree file included a total of 3,792 animals. Heritability and genetic correlations among the traits were estimated with a multivariate animal model under a Bayesian setting. Heritability estimates (posterior SD) for BINPPF, BINPMED, and BINPK were 0.35 (0.08), 0.37 (0.10), and 0.63 (0.09), respectively; for CFW and FD, estimates were 0.42 (0.09) and 0.43 (0.08), respectively. The genetic correlations between CFW and the 3 types of objectionable fibers were very low (i.e., <0.2). Thus selection for CFW is not expected to affect the number of such fibers in any direction. The same occurred for the genetic correlation between BINPK and FD. Genetic correlations between FD and BINPMED and FD and BINPPF were positive and favorable (0.50 and 0.56, respectively). Selecting for lower FD would decrease the numbers of objectionable fibers. The expected correlated responses in BINPPF, BINPMED, and BINPK when selecting for CFW were -0.03 (0.11), 0.03 (0.11), and 0.05 (0.18), respectively; when selecting for FD, the correlated responses were 0.26 (0.11), -0.26 (0.11), and -0.14 (0.16). Overall, this study reports novel information on genetic parameters for the presence of objectionable fibers and their associations with fleece traits in sheep. Our findings suggest that it could be possible to improve FD while at the same time reducing the content of BINPMED and BINPPF in wool; however, improvements in CFW are likely to have no effect on the numbers of objectionable fibers. PMID- 26812308 TI - Genetic parameters for docility, weaning weight, yearling weight, and intramuscular fat percentage in Hereford cattle. AB - Cattle behavior, including measures of docility, is important to beef cattle producers not only from a human safety perspective but also due to potential correlations to economically relevant traits. Field data from the American Hereford Association was used to estimate genetic parameters for chute score (CS; = 25,037), weaning weight (WW; = 24,908), yearling weight (YW; = 23,978), and intramuscular fat percentage (IMF; = 12,566). Single-trait and bivariate animal models were used to estimate heritabilities and genetic correlations. All models included fixed effects of sex and contemporary group, defined as herd-year season, and direct genetic and residual components were included as random effects. For CS and WW, additional random effects of maternal genetic and maternal permanent environment were also fitted. For CS, WW, YW, and IMF, heritability estimates were 0.27 +/- 0.02, 0.35 +/- 0.03, 0.36 +/- 0.02, and 0.27 +/- 0.02, respectively. Genetic correlations between CS and WW, CS and YW, CS and IMF, WW and YW, WW and IMF, and YW and IMF were -0.12 +/- 0.06, -0.10 +/- 0.05, 0.08 +/- 0.06, 0.47 +/- 0.05, -0.19 +/- 0.09, and -0.41 +/- 0.05, respectively. Heritability estimates for all traits suggest that they would respond favorably to selection and that selection for increased WW or YW could decrease marbling. Genetic correlations between CS and WW, YW, and IMF were all favorable but weak, suggesting that selection for improved docility will not have negative consequences on growth or carcass quality. Furthermore, maternal additive and maternal permanent environmental variances for CS were near 0, suggesting that their inclusion in National Cattle Evaluations is not warranted. PMID- 26812309 TI - Genetic parameters and crossbreeding effects of fat deposition and fatty acid profiles in Iberian pig lines. AB - The aim of this study was to estimate the genetic and environmental parameters and crossbreeding effects on fatty acid and fat traits in the Iberian pig. Our final goal is to explore target selection traits and define crossbreeding strategies. The phenotypes were obtained under intensive management from 470 animals in a diallelic experiment involving Retinto, Torbiscal, and Entrepelado lines. The data set was composed of backfat thickness at the fourth rib (BFT), intramuscular fat (IMF) in the longissimus thoracis (LT), and the fatty acid profile for IMF and subcutaneous fat (SCF) traits. Data were analyzed through a Bayesian bivariate animal model by using a reparameterization of Dickerson's model. The results obtained showed an important genetic determinism for all traits analyzed with heritability ranging from 0.09 to 0.67. The common environment litter effect also had an important effect on IMF (0.34) and its fatty acid composition (0.06-0.53) at slaughter. The additive genetic correlation between BFT and IMF (additive genetic correlation [] = 0.31) suggested that it would be possible to improve lean growth independent of the IMF with an appropriate selection index. Furthermore, the high additive genetic correlation ( = 0.68) found between MUFA tissues would seem to indicate that either the LT or SCF could be used as the reference tissue for MUFA selection. The relevance of the crossbreeding parameters varied according to the traits analyzed. Backfat thickness at the fourth rib and the fatty acid profile of the IMF showed relevant differences between crosses, mostly due to line additive genetic effects associated with the Retinto line. On the contrary, those for IMF crosses were probably mainly attributable to heterosis effects. Particularly, heterosis effects were relevant for the Retinto and Entrepelado crosses (approximately 16% of the trait), which could be valuable for a crossbreeding system involving these lines. PMID- 26812310 TI - Direct and correlated responses to selection in two lines of rabbits selected for feed efficiency under ad libitum and restricted feeding: I. Production traits and gut microbiota characteristics. AB - To get insights into selection criteria for feed efficiency, 2 rabbit lines have been created: the ConsoResidual line was selected for residual feed intake (RFI) with ad libitum feeding and the ADGrestrict line was selected for ADG under restricted feeding (-20% of voluntary intake). The first objective of this study was to evaluate, after 9 generations of selection, the direct and correlated responses to selection on production traits in the 2 lines for traits recorded during growth. Second, applying the 2 feeding conditions used for selection to both selected lines plus the control unselected line (generation 0, G0) in a 2 * 3 factorial trial, the line performances were compared and the gut microbiota of the lines was characterized. The correlated responses in feed conversion ratio (FCR) were remarkably equivalent in both selected lines (-2.74 genetic sigma) but correlated responses in other traits were notably different. In the ConsoResidual line, selection for decreased RFI resulted in a small negative correlated response in BW at 63 d old (BW63) and in a null response in ADG. In the ADGrestrict line, on the contrary, the correlated response in BW63 was substantial (+1.59 sigma). The 2 selected lines had a FCR reduced by 0.2 point compared with the G0 line, and the same difference was found in both feeding regimens ( < 0.001). Indeed, selection on ADG would lead to heavier animals with no significant reduction of feed costs, whereas selection on RFI leads to lower feed costs and no increase of animal BW under ad libitum feeding. Altogether, our results do not suggest any genotype * environment interaction in the response to feeding regimens. The intestinal microbial communities from efficient rabbits differed from their unselected counterparts in terms of fermentation end products and microbial phylotypes, suggesting a central role of these microbes in the better feed efficiency of the rabbits. PMID- 26812311 TI - Direct and correlated responses to selection in two lines of rabbits selected for feed efficiency under ad libitum and restricted feeding: II. Carcass and meat quality. AB - To get insights into selection criteria for feed efficiency, 2 rabbit lines have been created: the ConsoResidual line was selected for residual feed intake (RFI) with ad libitum feeding and the ADGrestrict line was selected for ADG under restricted feeding. The aim of the present study was to evaluate the impact on carcass and meat quality of the genetic selections. This comparison was performed using 2 different feeding strategies corresponding to the selection design. Carcass and meat quality traits were recorded for the 3 lines (ConsoResidual, ADGrestrict, and an unselected control [generation 0 {G0}]) in the 2 feeding systems (ad libitum and restricted) for 163 animals. Concerning the line effect, the BW at 63 d old was higher for the ADGrestrict line compared with the G0 and ConsoResidual lines ( < 0.0001). There was no line effect on the gastrointestinal tract. The rabbits did not exhibit a different carcass yield but showed different carcass traits. Indeed, the ConsoResidual rabbits had a higher hind leg yield ( < 0.0001) but no difference in the meat-to-bone ratio of the hind leg. On the contrary, the ADGrestrict line had a higher proportion of forelegs plus thoracic cage ( = 0.03). We also found lower perirenal ( < 0.0001) and scapular fat yields ( < 0.0001) in ConsoResidual rabbits. The ADGrestrict line had an intermediate perirenal fat yield compared with the other 2 lines. The G0 line always exhibited higher fat yields. Concerning meat quality, the ConsoResidual rabbits showed a lower ultimate pH ( < 0.0001) and higher water loss (drip and cooking loss; < 0.002) compared with the G0 and ADGrestrict rabbits. The feeding level had a strong effect on the gastrointestinal tract ( = 0.0004) and the carcass yield ( = 0.001). The latter was decreased in restricted rabbits. The effects of feeding strategy on meat quality were detrimental in the case of restricted feeding. Even if the ultimate pH was slightly higher in restricted rabbits ( = 0.0002), the carcass chilling loss ( = 0.0005) and the drip loss during 6 d ( < 0.0001) were higher. The selection on ADG with restricted access to feed seems to be less adversely correlated with carcass traits and meat quality traits but it leads to an increase in the live weight of the rabbits. Adversely, the selection on RFI, without affecting growth rate, would not modify age at slaughter because growth rate is not affected, but it might induce detrimental effects on meat quality. PMID- 26812312 TI - Insulinotropic action of bombesin-like peptides mediated by gastrin-releasing peptide receptors in steers. AB - The present study characterizes the receptor that mediates the insulinotropic action of bombesin-like peptides (BLP) in ruminants. Eight Holstein steers were randomly and intravenously injected with synthetic bovine gastrin-releasing peptide (GRP; 0.9 nmol/kg BW), neuromedin B (NMB; 0.9 nmol/kg BW), or neuromedin C (NMC; 0.9 nmol/kg BW), each alone or combined with the antagonist of GRP receptors N-acetyl-GRP-OCHCH (N-GRP-EE; 22.5 nmol/kg BW) or the antagonist of GH secretagogue receptor type 1a (GHS-R1a) [D-Lys]-GHRP-6 (21.5 nmol/kg BW). Blood samples were collected at -10, 0 (just before injection), 5, 10, 15, 20, 30, 45, 60, 75, and 90 min relative to injection time. Levels of injected peptides, insulin, and glucose in plasma were analyzed. Results showed that the peak of insulin levels was seen at 5 min after injection of NMC or GRP. Plasma glucose was observed in 2 phases; a significant rise followed a remarkable fall after NMC or GRP administration compared with injection of the vehicle ( < 0.05). On a same molar basis, effects of GRP on insulin and glucose were more potent than those of NMC ( < 0.05). The NMC-induced changes of insulin and glucose were completely blocked by N-GRP-EE, but [D-Lys]-GHRP-6 did not block any of these changes. Administration of NMB or N-GRP-EE alone did not change the circulating levels of insulin or glucose during any of the sampling time points ( > 0.05). These results indicated that the insulinotropic action of BLP is mediated by GRP receptors but not through a ghrelin/GHS-R1a pathway and that BLP may be involved in the regulation of glucose homeostasis in ruminants. PMID- 26812313 TI - Critical role of miR-125b in lipogenesis by targeting stearoyl-CoA desaturase-1 (SCD-1). AB - Alteration of gene expression tightly regulates lipogenesis. Stearoyl-CoA desaturase-1 (SCD-1), a key enzyme in lipogenesis, catalyzes the conversion of SFA to MUFA, and inhibition of its activity impairs lipid synthesis. As posttranscriptional regulators, microRNAs are involved in many pathways of lipid metabolism; however, their effect on SCD-1 has not been reported. In this study, miR-125b was identified as a potential regulator of SCD-1 using bioinformatics analysis. Here, we validated SCD-1 as the target of miR-125b using a dual luciferase assay. During adipogenesis, a synthetic mimic or inhibitor was used to overexpress or reduce the expression of miR-125b in porcine adipocytes. Overexpression of miR-125b reduced the accumulation of lipid droplets and triglycerides concentration and repressed SCD-1 protein expression and MUFA composition. The inhibitor had the reverse effect. Small interfering RNA against tested in adipocytes further proved the direct correlation between miR-125b and SCD-1. Moreover, in vivo experiments in mice showed that injection of miR-125b expression vector decreased the hepatic triglycerides concentration relative to saline. This study indicated that miR-125b regulates lipogenesis by targeting SCD 1; therefore, miR-125b might be applied in therapy of lipid metabolism disorders. PMID- 26812314 TI - Effects of heat stress on metabolism, digestibility, and rumen epithelial characteristics in growing Holstein calves. AB - To distinguish between the direct effects of heat stress (HS) and reduced DMI on metabolic and physiological variables, morphometry, and gene expression of transporters involving in ruminal VFA absorption, 16 Holstein bull calves (178.1 +/- 7.55 kg of BW) were used in a randomized complete design using 2 experimental periods. In period 1 (P1), all animals were housed in thermoneutral (TN) conditions (20.7 +/- 3.0 degrees C and a temperature-humidity index [THI] of 65.2 +/- 3.1) and fed ad libitum for 8 d. In period 2 (P2; 9 d), half of the calves ( = 8) were subjected to HS condition (29.9 to 41.0 degrees C and a THI >= 85 for 8 h/d) and the other half ( = 8) were maintained in TN conditions but were pair fed (pair-fed thermoneutral [PFTN]) to the HS calves. Heat stress decreased DMI (20%; < 0.01) and, by design, PFTN calves had similar reduced intakes. During P1, ADG was similar between groups (1.7 kg/d), but ADG was reduced similarly for both groups (0.14 kg/d) during P2 ( < 0.01). Compared with P1, HS calves had decreased plasma glucose levels (12.5%; < 0.01) in P2. Basal insulin levels increased in P2 for HS calves (71%; < 0.03), but there was no difference between periods for PFTN calves. Circulating NEFA concentrations did not differ between periods in the HS calves, but PFTN animals had increased basal NEFA levels (100%; < 0.01). Compared with P1, HS calves had increased blood urea nitrogen concentration in P2 ( < 0.01) but blood urea nitrogen did not differ between periods in the PFTN calves. Heat stress had no measurable effect on nutrient digestibility. Rumen papillae height increased (51%; < 0.04) in HS calves whereas papillae top width decreased (40%; < 0.03), but there was no difference between treatments for other morphometric parameters. Gene expression of VFA transporters in rumen epithelium was not affected by thermal treatments. These results confirmed that short-term HS in the current study had no effect on diet digestibility, rumen morphology, or VFA transporters genes. Therefore, HS-induced decrease in DMI is in large part responsible for gross changes in BW in growing calves (albeit tissue composition of growth is not unknown). PMID- 26812315 TI - Evaluating blood perfusion of the corpus luteum in beef cows during fescue toxicosis. AB - The aim of this study was to determine if fescue toxicosis altered blood perfusion in the corpus luteum (CL) and peripheral concentrations of progesterone in cattle. The estrous cycles of 36 nonpregnant Angus or Charolais cows were synchronized in 2 replicates using the CO-Synch+CIDR protocol. Seven days after initiation of the protocol, cows were assigned (d 0) to 1 of 2 dietary treatments: 2.5 kg of 1) Kentucky-31 endophyte-infected (KY31; = 14) or 2) MaxQ novel endophyte (MaxQ; = 12) tall fescue seed. On d 7, ovaries were examined using ultrasonography, and only cows that had 1 CL present remained on the study ( = 26). Images of blood perfusion of CL, blood samples, rectal temperatures, and blood pressure of tails were collected on d 10, 13, 15, and 18. Images of CL blood perfusion were analyzed using ImageJ software for pixel density, and scored visually (0 to 9 with 0 = no perfusion, 9 = complete perfusion) by 2 independent technicians. The MIXED procedure of SAS was used with day as a repeated measure. Least squares means and SEM are reported. Cows receiving KY31 had greater rectal temperatures ( 0.003; 38.76 +/- 0.08 degrees C) than those receiving MaxQ (38.44 +/- 0.08 degrees C), providing evidence that the cows treated with KY31 were influenced by fescue toxicosis. Pulse pressure and mean arterial pressure were decreased ( < 0.01) in cows receiving KY31 (55.26 +/- 2.81 and 80.06 +/- 2.72 mmHg, respectively) than MaxQ (66.58 +/- 3.03 and 91.38 +/- 2.93 mmHg, respectively). Concentrations of progesterone were similar ( = 0.54) between cows receiving KY31 (6.04 +/- 0.53 ng/mL) or MaxQ (6.36 +/- 0.63 ng/mL). Pixel densities ( = 0.14) and visual perfusion scores were similar ( = 0.11) between cows receiving KY31 (1477.20 +/- 655.62 pixels and 2.23 +/- 0.34, respectively) or MaxQ (2934.70 +/- 718.20 pixels and 3.00 +/- 0.36, respectively). Mean CL volume was similar ( 0.95) between treatments. In conclusion, blood perfusion of CL or peripheral concentrations of progesterone were not altered at the onset of fescue toxicosis in this short-term study, indicating that a decrease in blood perfusion of the CL may not be a primary mechanism involved in decreased reproductive efficiency of cattle during fescue toxicosis. PMID- 26812316 TI - Litter-of-origin trait effects on gilt development. AB - The preweaning litter environment of gilts can affect subsequent development. In a recent experiment designed to test the effects of diet on gilt development, litter-of-origin traits including individual birth weights, immunocrits (a measure of colostrum intake), sow parity, number weaned, and individual weaning weights were collected for approximately 1,200 gilts that were progeny of approximately 300 sows. Subsequently, BW, LM area, and backfat were measured at 100 d of age and at 28-d intervals until slaughter (260 d of age). From 160 d of age to slaughter, gilts were observed daily for estrus. At slaughter, the reproductive tract and 1 mammary gland were recovered. The reproductive tract was classified as cyclic or prepubertal; the number of corpora lutea was counted. Uterine horn lengths and ovarian dimensions were measured. Uterus and ovary samples from every 10th gilt were prepared for histological evaluation of uterine gland development and follicle counts, respectively. Mammary gland tissue protein and fat were assayed. Day of the estrous cycle at slaughter was calculated using the first day of the most recent standing estrus (d 0) recorded previous to slaughter. Each gilt development trait was analyzed for association with each litter-of-origin trait, after adjusting for dietary treatment effects. Uterine length, ovarian dimensions, mammary gland protein and fat, and uterine gland development were also adjusted for day of the estrous cycle at slaughter. All litter-of-origin traits were associated ( < 0.05) with growth traits. Top-down (backward elimination) multiple regression analysis indicated that BW and LM accretion in gilts was positively associated with immunocrit ( < 0.01), birth weight ( < 0.01), preweaning growth rate ( < 0.01), and parity ( < 0.01). Backfat accretion was positively associated with preweaning growth rate ( < 0.01), number weaned ( < 0.05), and parity ( < 0.05). Age at puberty was associated with birth weight (positive; < 0.01) and preweaning growth rate (negative; < 0.01). Total uterine length was positively associated with only birth weights ( < 0.05). Mammary gland protein was negatively associated with preweaning growth ( < 0.01). Mammary gland fat was positively associated with birth weight and number of piglets weaned ( > 0.05). These results indicate that colostrum consumption, birth weights, preweaning growth rate, number weaned, and parity are associated with gilt development traits during later life. PMID- 26812317 TI - Effects of corn type and fasting time before slaughter on growth and plasma index in weaning pigs. AB - A 2 * 2 factorial experiment was conducted to evaluate the effects of dietary corn type (waxy corn [WC] vs. nonwaxy corn [NC]) and fasting period (2 h vs. 12 16 h) before slaughter on growth and plasma index in weaning pigs. Twenty-four crossbred barrows (8.26 +/- 0.47 kg) were allotted to 4 treatments with 6 replications of 1 pig per replicate metabolism cage. Waxy corn contained less fat, a lower amylase:amylopectin ratio, more CP, and more starch than NC. Pigs fed the WC diet had lower jejunum digesta pH compared with those fed the NC diet ( < 0.05). Maltase activity in the jejunum and ileum mucosa ( < 0.01), sucrose activity in the ileum mucosa ( < 0.01), and amylase activity in the pancreas and jejunum digesta ( < 0.05) were increased in pigs fed the WC diet relative to those fed the NC diet. But the total tract apparent digestibility (TTAD) of starch and CP was lower for the WC group ( < 0.05). Ingestion of the NC diet resulted in higher ( < 0.05) ADG and ADFI in the second week but did not affect ADG ( = 0.091) and the feed:gain ratio (F:G; = 0.077) during the whole experiment period. The plasma glucose ( < 0.01) concentration was higher and high-density lipoprotein cholesterol (HDL-C; < 0.01) concentrations was lower in the hepatic portal vein in pigs fed the WC diet relative to those fed the NC diet. Fasting 2 h before slaughter decreased the jejunum and ileum digesta pH compared with the 12-h fasting group ( < 0.01). Villus height increased in the duodenum ( < 0.01) and jejunum ( < 0.05) and the villus height:crypt depth ratio increased in the duodenum ( < 0.05) of pigs after shortening the fasting period before slaughter. Shortening the fasting time before slaughter resulted in higher plasma glucose ( < 0.05) concentrations and a higher HDL-C:low-density lipoprotein cholesterol (LDL-C) ratio ( < 0.05) whereas the LDL-C ( < 0.05) concentrations were reduced in the hepatic portal vein. The results of this experiment indicate that although the production performance of both WC and NC diets is equal, the glucose concentration is higher and HDL-C is lower in the portal vein for the WC diet, and fasting time before slaughter has an influence on the plasma index and intestinal morphology in weaning pigs. PMID- 26812318 TI - Prediction of the metabolizable energy requirements of free-range laying hens. AB - This experiment was conducted with the aim of estimating the ME requirements of free-range laying hens for maintenance, weight gain, and egg production. These experiments were performed to develop an energy requirement prediction equation by using the comparative slaughter technique and the total excreta collection method. Regression equations were used to relate the energy intake, the energy retained in the body and eggs, and the heat production of the hens. These relationships were used to determine the daily ME requirement for maintenance, the efficiency energy utilization above the requirements for maintenance, and the NE requirement for maintenance. The requirement for weight gain was estimated from the energy content of the carcass, and the diet's efficiency energy utilization was determined from the weight gain, which was measured during weekly slaughter. The requirement for egg production was estimated by considering the energy content of the eggs and the efficiency of energy deposition in the eggs. The requirement and efficiency energy utilization for maintenance were 121.8 kcal ME/(kg?d)and 0.68, respectively. Similarly, the NE requirement for maintenance was 82.4 kcal ME/(kg?d), and the efficiency energy utilization above maintenance was 0.61. Because the carcass body weight and energy did not increase during the trial, the weight gain could not be estimated. The requirements for egg production requirement and efficiency energy utilization for egg production were 2.48 kcal/g and 0.61, respectively. The following energy prediction equation for free-range laying hens (without weight gain) was developed: ME /(hen ? d) = 121.8 * W + 2.48 * EM, in which W = body weight (kg) and EM = egg mass (g/[hen ? d]). PMID- 26812319 TI - Bixin uptake and antioxidative effect and role in immunoregulation in domestic cats. AB - Bixin, a carotenoid found in the seed of the Annatto plant, , is a potent antioxidant. Carotenoids are readily absorbed from the diet; therefore, the purpose of this study was to examine uptake of bixin by plasma, lipoproteins, and leukocytes after dietary supplementation in domestic cats and to assess effects on immune response. Female domestic short hair cats (3 yr old; 4.79 +/- 0.13 kg BW) were fed a single dose of 0, 1, 5, or 10 mg bixin, and blood was taken at 0, 1, 2, 4 and 8 h after administration ( = 6/treatment) to determine acute absorption rate. Then, bixin was fed daily for 14 d to examine steady-state plasma concentrations and subcellular distribution. Following these preliminary experiments, cats ( = 8/treatment) were fed diets containing 0, 1, 5, or 10 mg bixin/d for 16 wk and blood was collected on wk 0, 6, 12, and 16 for analysis of leukocyte subpopulations, cell-mediated responsiveness, and inflammatory and oxidative biomarkers. Maximal uptake in plasma occurred 1 h after a single oral dose of bixin, with a maximal concentration of 0.119 MU and elimination half-life of 1.8 to 2.2 h. Daily feeding of bixin showed a steady-state plasma concentration of 0.110 MU at the greatest doses. Bixin was primarily associated with the high-density lipoprotein fraction of blood lipoproteins and was primarily distributed in mitochondrial fractions (58-59%) of but also in microsomal and nuclear fractions (37-44%). Leukocyte subpopulations in blood were variably affected by dietary bixin, with an increase ( < 0.05) in total T cells but a concurrent decrease ( < 0.05) in CD18+ and B cell subpopulations. However, plasma IgG increased ( < 0.05) in the 10-mg treatment group by wk 6. Lymphoproliferation was stimulated ( < 0.05) in the 5-mg bixin treatment group by wk 16, and delayed-type hypersensitivity response increased after nonspecific antigenic challenge. Conversely, when a specific challenge of vaccine was assessed on wk 12 and 16, responsiveness decreased ( < 0.05) in the 10-mg bixin treatment group. Bixin supplementation surprisingly caused an increase ( < 0.05) in alpha-acid glycoprotein but had no effect on natural killer cell activity, other subpopulations of leukocytes, or 8-oxo-2>-deoxyguanosine, a DNA damage biomarker. This experiment demonstrated dose-dependent uptake of bixin in plasma and blood lipoproteins and distribution in leukocyte subcellular components and an impacted immune response through cell-mediated and humoral actions. PMID- 26812320 TI - Uptake and immunomodulatory role of bixin in dogs. AB - Carotenoids are readily absorbed from the diet and distributed in blood leukocyte subcellular organelles. Bixin, a potent bioactive found in the seed of the Annatto plant, , possesses antioxidant and anti-inflammatory properties. The purpose of this study was to determine the uptake of bixin by plasma, lipoproteins, and leukocytes in domestic dogs and to examine immunoprotective properties. To determine uptake kinetics, female Beagle dogs (2 yr; 9.1 +/- 0.1 kg BW) were first fed a single dose by oral gavage of 0, 5, 10, 20, or 40 mg bixin, with blood collected at 0 to 16 h after administration ( = 6/treatment), and then fed daily with 0, 5, 10, 20, or 40 mg bixin/d, with blood collected at 0, 1, 2, 4, 6, 10, and 14 d. In a consecutive experiment, cell-mediated and humoral responses as well as oxidative biomarkers were measured following 16 wk of dietary supplementation with 0, 5, 10, or 20 mg bixin/d. Maximal absorption in plasma occurred by 0.5 h with an elimination half-life of 2.6 to 3.3 h after a single dose of bixin. Steady-state plasma concentrations were 0.053 MU after 14 d of 40 mg bixin/d. The majority of subcellular bixin was found in the leukocyte mitochondria and was associated with the high-density lipoprotein and low-density lipoprotein fractions of lipoproteins. Specific (vaccine) response increased ( < 0.05) but nonspecific mitogen response was unchanged after 12 wk of dietary bixin, as assessed by a delayed-type hypersensitivity assay. Both B cell plasma leukocyte subpopulations at 6 and 16 wk and IgG plasma concentration at 12 wk in the 10-mg treatment group increased ( < 0.05), although IgM production and other cell populations were unaffected. In addition, 8-oxo-2'-deoxyguanosine (8-OHdG), a DNA damage biomarker, was substantially reduced ( < 0.05) in all treatment groups by wk 16, and C-reactive protein (CRP) was suppressed at wk 12 ( < 0.05). Dietary supplementation with bixin showed no changes in lymphoproliferation in response to in vitro mitogenic challenge and had no effect in enhancing natural killer cell activity. In conclusion, bixin was readily absorbed in a dose dependent manner in blood following oral administration and was then taken up by leukocytes, where it was primarily distributed to mitochondria but in other subcellular organelles as well. Bixin also appeared to stimulate immune response, as seen with cell-mediated responses, and exerted anti-inflammatory (reduced CRP) as well as antioxidative (reduced 8-OHdG) effects in dogs. PMID- 26812321 TI - Effects of feeding diets containing distillers' dried grains with solubles and wheat middlings with equal predicted dietary net energy on growth performance and carcass composition of growing-finishing pigs. AB - This experiment evaluated the effects of feeding distillers' dried grains with solubles (DDGS) and wheat middlings (WM) in diets with similar estimated NE content on growth performance and carcass characteristics of growing-finishing pigs. Pigs ( = 384; 29.1 +/- 3.6 kg initial BW) were blocked by initial BW, and within blocks, pens were randomly allotted to 1 of 4 dietary treatments (8 pigs/pen and 12 replicates/treatment) in a 4-phase feeding program (29 to 50, 50 to 75, 75 to 100, and 100 to 120 kg BW). Dietary treatments were arranged in a 2 * 2 factorial design and formulated to consist of: 1) corn and soybean meal (CON), 2) CON with 30% DDGS, 3) CON with 15% WM, and 4) CON with 30% DDGS and 15% WM. Diets met or exceeded nutrient requirements published by the and were formulated to contain the same concentrations of standardized ileal digestible (SID) Lys and meet or exceed minimum SID AA to Lys ratios within phases. No significant interactions for DDGS * WM * phase or DDGS * WM were observed for all growth performance criteria. Pigs fed diets containing 30% DDGS had reduced ( < 0.05) ADFI (1.76 vs. 1.86 kg/d) and ADG (0.85 vs. 0.91 kg/d) compared with pigs fed diets with no DDGS in phase 1 but not in other phases. The G:F of pigs fed diets containing DDGS was not different during phase 1 to 3 but was greater ( < 0.01) in phase 4 (0.313 vs. 0.291) compared with that of pigs fed diets with no DDGS. Pigs fed diets containing 15% WM had similar ADFI and G:F but reduced ( < 0.05) ADG (0.86 vs. 0.90 kg/d) compared with pigs fed diets without WM in phase 1, but no difference in ADG was observed in phases 2 to 4. No DDGS * WM interaction was observed for carcass traits. Pigs fed diets containing 30% DDGS had reduced ( < 0.01) HCW (86.5 vs. 89.9 kg), carcass yield (72.3 vs. 73.6%), LM area (45.0 vs. 47.9 cm), and percentage of carcass fat-free lean (52.1 vs. 53.4%), but backfat depth was not affected compared with pigs fed diets with no DDGS. Pigs fed diets containing 15% WM had lower carcass yield (72.7 vs. 73.1%; < 0.05) and HCW (87.7 vs. 88.7 kg; < 0.10) than pigs fed diets with no addition of WM, but other carcass traits were not affected. In conclusion, overall ADG and G:F were not affected by feeding 30% DDGS or 15% WM when diets were formulated on the NE basis, but more accurate and dynamic estimation of NE content for DDGS sources is needed to optimize caloric efficiency at different physiological ages of pigs. PMID- 26812322 TI - The effect of increasing the dietary valine-to-lysine ratio on sow metabolism, milk production, and litter growth. AB - A study was conducted to investigate the effect of increasing the dietary valine to-lysine ratio (Val:Lys) for lactating sows weaning more than 12 piglets. Five hundred fifty-eight sows (parity 1 to 4) were allotted to 6 dietary treatments from 2 d postpartum, when litters were standardized to 14 piglets. Diets were analyzed to have a total dietary Val:Lys of 0.84, 0.86, 0.88, 0.90, 0.95, or 0.99:1. On all 558 sows, BW, back fat thickness (BF), and litter weight were registered at d 108 of gestation and d 2 and 25 (weaning) postpartum. On a subsample of 72 sows, additional measurements were made: sow BW and BF were measured on d 17 and litter weight was measured on d 10 and 17, and blood and urine samples were collected weekly. The litter size at weaning was not affected by the dietary Val:Lys ( = 0.23) and, on average, the sows weaned 13.0 +/- 1.1 piglets. Average daily gain of the litter (2.93 +/- 0.53 kg/d; = 0.84), litter weight at weaning ( = 0.67), the average milk yield (11.3 +/- 1.4 kg/d; = 0.49), and milk contents of fat ( = 0.57), protein ( = 0.18), and lactose ( = 0.20) were not affected by the dietary Val:Lys. Increasing the dietary Val:Lys increased the milk concentration of Val ( < 0.05) and Ile ( < 0.01). The change in sow BW and BF were similar for all sows from d 2 to 17, d 17 to 25, and d 2 to 25 ( > 0.05). During lactation, sows, on average, had a BW and back fat loss of 22.1 +/- 12.7 kg and 2.9 +/- 1.7 mm, respectively. Plasma concentrations of glucose ( = 0.26), lactate ( = 0.95), urea N ( = 0.84), NEFA ( = 0.24), and creatinine ( = 0.42); urine concentration of creatinine ( = 0.57); and concentrations of AA in whole blood ( > 0.05) were not affected by the dietary Val:Lys. In conclusion, there was no effect of increasing the total dietary Val:Lys above 0.84:1 on sow metabolism and litter performance during lactation. PMID- 26812323 TI - Effect of heat stress on the endogenous intestinal loss of amino acids in growing pigs. AB - Heat stress (HS) increases the death of intestinal cells in pigs, which, in turn, may elevate the endogenous intestinal loss (EIL) of proteins and AA. An experiment was conducted to analyze the effect of HS on the AA composition of intestinal endogenous proteins and the EIL of AA in pigs. Eight pigs (25.2 +/- 1.2 kg initial BW) were surgically implanted with T-type cannulas at the end of the small intestine. After surgery recovery, during the subsequent 7 d, all pigs were adapted to a protein- and AA-free diet and trained to consume the same amount of feed twice a day. All pigs were housed under thermoneutral (TN) conditions (22 +/- 2 degrees C) during this time. The following day, all pigs were still under TN conditions and ileal content was collected during 12 consecutive hours, at the end of which and for the following 8 d the pigs were exposed to natural HS conditions (31 to 37 degrees C). Ileal content was collected again on d 2 (HS at d 2 [HSd2]) and 8 (HS at d 8 [HSd8]). Body temperature (BT) was measured in another group of 8 pigs every 15 min during the whole study. The average BT at HSd2 (39.6 degrees C) was higher ( < 0.05) compared with both TN conditions (38.6 degrees C) and HSd8 (38.8 degrees C), but it did not differ between TN conditions and HSd8. The AA composition of endogenous intestinal protein was not affected by HS. The EIL of Arg and His were greater ( < 0.05) and the EIL of Thr and Phe tended to be greater ( <= 0.10) at HSd2 than in TN conditions; the EIL of Pro was greater ( = 0.01) at HSd8. The EIL of the remaining AA was not affected by HS. Although HS increased the EIL of Arg and His within the first 2 d, it appeared that normal EIL was shortly reestablished. These data show that acute HS does not affect the AA composition of intestinal endogenous proteins in growing pigs and that the EIL of AA may not be critical in growing pigs acclimated to high ambient temperature. Nevertheless, the increased EIL of Arg and Thr at HSd2 indicate that HS might affect the integrity of the intestinal epithelium of pigs during the first day of their exposure to high ambient temperature. PMID- 26812324 TI - Dietary spray-dried chicken plasma improves intestinal barrier function and modulates immune status in weaning piglets. AB - The objective of this study was to evaluate the effects of dietary addition of spray-dried chicken plasma (SDCP) as a replacement for spray-dried porcine plasma (SDPP) on serum biochemistry, intestinal barrier function, immune parameters, and the expression of intestinal development-related genes in weaning pigs. One hundred and forty-four 25-d-old weaning piglets with BW of 6.43 +/- 0.39 kg were randomly allotted to 1 of 4 dietary treatments: 1) CON (basal diet; control), 2) SDPP (containing 5% SDPP), 3) SDPP + SDCP (containing 2.5% SDPP and 2.5% SDCP), and 4) SDCP (containing 5% SDCP). After a 28-d trial, 6 pigs from each treatment were randomly selected to collect serum and intestinal samples. On d 14 after the initiation of the trial, pigs in the SDPP, SDPP + SDCP, and SDCP groups had an increase ( < 0.05) in serum concentrations of total protein and IgG and a decrease ( < 0.05) in activities of alanine aminotransferase and diamine oxidase compared with the CON group. In the jejunum, supplementation with SDPP and SDCP reduced ( < 0.05) the concentration of tumor necrosis factor-alpha (TNF-alpha) and upregulated ( < 0.05) the mRNA levels of zonula occludens 1 (ZO-1), zonula occludens 2 (ZO-2), occludin (OCLN), Toll-like receptor 2 (TLR2), glucagon-like peptide 2 (GLP2), and IGF-1 compared with the CON group. In the ileum, feeding SDPP, SDPP + SDCP, and SDCP decreased ( < 0.05) the concentrations of TNF-alpha and secretory IgA (sIgA) and upregulated ( < 0.05) the mRNA levels of claudin 1 (CLDN-1) and TLR2 compared with feeding CON. However, there were no differences among the SDPP, SDPP + SDCP, and SDCP groups. Furthermore, supplementation with SDCP reduced ( < 0.05) the concentration of IL-10 and upregulated ( < 0.05) the mRNA levels of GLP-2, mucin 2 (MUC2), and trefoil factor family 3 (TFF3) in the ileum compared with feeding CON. Collectively, the current results indicate that dietary addition of SDCP has a beneficial influence on the health condition of weaning pigs by alleviating liver damage, promoting intestinal development, improving intestinal barrier function, and reducing overstimulation of immune response. The efficacy of SDCP is comparable to that of SDPP. PMID- 26812326 TI - Lactoferrin supplementation of the neonatal calf has no impact on immunoglobulin G absorption and intestinal development in the first days of life. AB - The objectives of this study were to determine if newborn calves receiving supplemental lactoferrin (LF) had improved IgG uptake and if supplemental LF enhanced intestinal development through estimation of xylose uptake. Twenty-four newborn Holstein bull calves were randomly assigned to 1 of 2 treatments: 0 or 1 g/d of supplemental LF. Calves were fed pooled maternal colostrum from 9 cows in 2 feedings: at birth and 12 h later. Calves consumed in excess of 200 g of IgG. Blood samples were taken before colostrum feeding (0 h) and at 12, 18, and 24 h after birth. Blood samples were analyzed for IgG concentration. On d 2 of life, calves were fed milk replacer with the added LF and 0.5 g/kg of BW xylose to determine if supplemental LF affected intestinal development. Blood was sampled at 0, 0.5, 1, 2, 3, 4, 6, 8, and 12 h after the xylose dose. All calves attained passive transfer and supplemental LF did not affect IgG uptake ( >= 0.36) or apparent efficiency of absorption of IgG ( = 0.49). Lactoferrin did not enhance rate of absorption at any time point ( >= 0.36). There were no differences in xylose ( = 0.28) or glucose ( = 0.27) area under the curve values in calves supplemented with either 0 or 1 g/d LF. Lactoferrin did not enhance IgG uptake during the first 24 h or intestinal development in calves on the second day of life. PMID- 26812325 TI - Urinary excretion of dietary Maillard reaction products in healthy adult female cats. AB - During processing of foods, the Maillard reaction occurs, resulting in the formation of advanced Maillard reaction products (MRP). Varying amounts of MRP have been found in commercially processed pet foods. Dietary MRP can be absorbed and contribute to the endogenous pool of MRP and possibly the etiology of age related diseases. The aim of the present study was to determine urinary excretion of dietary MRP in cats fed commercial moist and dry foods. A pilot study with 10 cats, conducted to determine the adaptation time required for stable urinary excretion of MRP when changing to a diet with contrasting MRP content, showed an adaptation time of 1 d for all components. In the main study, 6 commercially processed dry and 6 moist diets were fed to 12 adult female cats in 2 parallel randomized, 36-d Latin square designs. The 24-h urine was collected quantitatively using modified litter boxes, and fructoselysine (FL), carboxymethyllysine (CML), and lysinoalanine (LAL) were analyzed using ultra high performance liquid chromatography (UHPLC) - mass spectrometer. Daily urinary excretion of FL and CML showed a positive relationship with daily intake in the dry ( = 0.03 and < 0.01, respectively) and moist ( < 0.01) foods. For LAL, no significant relationship was observed. Urinary recovery (% ingested) showed a negative relationship with daily intake for FL, CML, and LAL in the dry foods ( < 0.01, < 0.01, and = 0.08, respectively) and for CML and LAL in the moist foods ( < 0.01). The observed increase in urinary excretion with increasing dietary intake indicates that dietary MRP were absorbed from the gastrointestinal tract of cats and excreted in the urine. The adaptation time with change in diet indicates a likely effective excretion of MRP. Minimum apparent absorption of FL, CML, and LAL was found to range between 8% and 23%, 25% and 73%, and 6% and 19%, respectively. The observed decrease in urinary recovery suggests a limiting factor in digestion, absorption, metabolism, or urinary excretion. This study shows that dietary MRP in commercial diets are absorbed and excreted via the kidneys in cats. PMID- 26812327 TI - Effects of varying ruminally undegradable protein supplementation on forage digestion, nitrogen metabolism, and urea kinetics in Nellore cattle fed low quality tropical forage. AB - Effects of supplemental RDP and RUP on nutrient digestion, N metabolism, urea kinetics, and muscle protein degradation were evaluated in Nellore heifers () consuming low-quality signal grass hay (5% CP and 80% NDF, DM basis). Five ruminally and abomasally cannulated Nellore heifers (248 +/- 9 kg) were used in a 5 * 5 Latin square. Treatments were the control (no supplement) and RDP supplementation to meet 100% of the RDP requirement plus RUP provision to supply 0, 50, 100, or 150% of the RUP requirement. Supplemental RDP (casein plus NPN) was ruminally dosed twice daily, and RUP supply (casein) was continuously infused abomasally. Jugular infusion of [NN]-urea with measurement of enrichment in urine was used to evaluate urea kinetics. The ratio of urinary 3-methylhistidine to creatinine was used to estimate skeletal muscle protein degradation. Forage NDF intake (2.48 kg/d) was not affected ( >= 0.37) by supplementation, but supplementation did increase ruminal NDF digestion ( < 0.01). Total N intake (by design) and N retention increased ( < 0.001) with supplementation and also linearly increased with RUP provision. Urea entry rate and gastrointestinal entry rate of urea were increased by supplementation ( < 0.001). Supplementation with RUP linearly increased ( = 0.02) urea entry rate and tended ( = 0.07) to linearly increase gastrointestinal entry rate of urea. Urea use for anabolic purposes tended ( = 0.07) to be increased by supplementation, and RUP provision also tended ( = 0.08) to linearly increase the amount of urea used for anabolism. The fraction of recycled urea N incorporated into microbial N was greater ( < 0.001) for control (22%) than for supplemented (9%) heifers. Urinary 3 methylhistidine:creatinine of control heifers was more than double that of supplemented heifers ( < 0.001). Control heifers reabsorbed a greater ( < 0.001) fraction of urea from the renal tubule than did supplemented heifers. Overall, unsupplemented heifers had greater mobilization of AA from myofibrillar protein, which provided N for urea synthesis and subsequent recycling. Supplemental RUP, when RDP was supplied, not only increased N retention but also supported increased urea N recycling and increased ruminal microbial protein synthesis. PMID- 26812328 TI - Effects of chromium supplementation to feedlot steers on growth performance, insulin sensitivity, and carcass characteristics. AB - Objectives were to determine the effects of chromium propionate supplementation on growth performance, insulin and glucose metabolism, and carcass characteristics of beef cattle. Steers ( = 34) were stratified by BW and assigned to 1 of 2 treatments: 1) no supplemental Cr (Cont) or 2) 3 mg supplemental Cr.steer.d (CrP). Both supplements, Cont and CrP, were delivered via 0.454 kg ground corn top-dressed on the basal diet. There was no effect ( >= 0.45) of CrP on ADG, DMI, G:F, or final BW. However, steers fed CrP needed more ( = 0.10) days on feed (DOF) to achieve the same carcass back fat (BF) as steers fed Cont. There were no effects ( >= 0.41) of CrP on HCW, BF, or KPH. Steers fed CrP had increased ( = 0.01) dressing percentage (DP) and tended to have a 4.21 cm greater LM area ( = 0.15), decreased marbling scores ( = 0.11), and decreased intramuscular fat ( = 0.11) compared to steers fed Cont. There were no differences ( >= 0.25) in quality or yield grade distributions. A glucose tolerance test was conducted early (21 DOF) and late (98 DOF) in the finishing phase. There was a feedlot treatment (FT) * time * DOF interaction ( = 0.08) for glucose concentrations, but no other interactions ( >= 0.21) for glucose or insulin concentrations. There were no FT * DOF interactions ( >= 0.21) for insulin area under the curve (iAUC), insulin:glucose ratio, insulin or glucose baseline, or peak insulin or glucose concentrations. At 21 DOF, steers fed CrP had decreased glucose area under the curve (gAUC; = 0.01), decreased glucose clearance rate (; = 0.02), and increased glucose half-life (T; = 0.07) compared to steers fed Cont; however, by 98 DOF, no differences were observed between treatments. At 98 DOF, all steers, regardless of treatment, had increased ( < 0.01) peak glucose and insulin, , iAUC, insulin:glucose ratio, and baseline insulin when compared to values at 21 DOF, but gAUC and T decreased ( < 0.01). Although steers fed CrP tended ( = 0.11) to have increased baseline glucose concentrations compared to steers fed Cont, CrP supplementation did not affect ( >= 0.17) other measures of glucose or insulin. Results of this study indicate that CrP increased DP and tended to increase LM area but tended to decrease intramuscular fat, with no effect on growth performance. With increased DOF, all steers became more insulin resistant, using more insulin to clear less glucose, and these effects were not mitigated by CrP supplementation. PMID- 26812329 TI - Biofuel feedstock and blended coproducts compared with deoiled corn distillers grains in feedlot diets: Effects on cattle growth performance, apparent total tract nutrient digestibility, and carcass characteristics. AB - Crossbred steers (British * Continental; = 192; initial BW 391 +/- 28 kg) were used to evaluate the effects of feeding ethanol coproducts on feedlot cattle growth performance, apparent nutrient digestibility, and carcass characteristics. Steers were blocked by initial BW and assigned randomly to 1 of 6 dietary treatments within block. Treatments (replicated in 8 pens with 4 steers/pen) included 1) control, steam-flaked corn-based diet (CTL), 2) corn dried distillers grains with solubles (DGS; DRY-C), 3) deoiled corn dried DGS (DRY-CLF), 4) blended 50/50 corn/sorghum dried DGS (DRY-C/S), 5) sorghum dried DGS (DRY-S), and 6) sorghum wet DGS (WET-S). Inclusion of DGS was 25% (DM basis). The DGS diets were isonitrogenous, CTL was formulated for 13.5% CP, and all diets were balanced for ether extract. Final shrunk BW, ADG, and DMI did not differ among CTL and DGS treatments ( >= 0.19). Overall G:F did not differ from CTL for DRY-C, DRY-CLF, or WET-S ( >= 0.12); however, G:F was 9.6% less for DRY-S compared with CTL ( < 0.01) and tended ( = 0.09) to be less for DRY-C/S than CTL. For grain source, ADG and G:F were less for DRY-S vs. DRY-C ( < 0.05), but blending DRY-C/S tended ( = 0.07) to increase ADG and increased ( = 0.05) carcass-adjusted G:F vs. DRY-S. For WET-S, final BW and ADG were greater ( < 0.05), and G:F tended ( = 0.06) to be greater than for DRY-S. There was no difference in ADG, DMI, or G:F of steers fed DRY-C vs. DRY-CLF ( >= 0.35). Apparent DM and OM digestibility did not differ for CTL, DRY-C, DRY-CLF, and WET-S ( >= 0.30) but were lower for DRY-C/S and DRY-S ( < 0.05). Nutrient digestibility was lower for DRY-S vs. DRY-C ( < 0.01), but apparent digestibility of OM, DM, NDF, ADF, CP, ether extract, and starch were increased ( < 0.01) for DRY-C/S vs. DRY-S. Although starch digestibility did not differ between DRY-S and WET-S ( 0.18), digestibility of other measured nutrients was greater for WET-S vs. DRY-S ( < 0.01). Ether extract digestibility was greater for DRY-CLF vs. DRY-C ( < 0.05). Carcass weight, dressing percent, and marbling score did not differ between CTL and DGS diets ( >= 0.23). For DRY-S, HCW was lower than for DRY-C ( = 0.02); however, compared with DRY-S, HCW tended to be greater for DRY-C/S ( = 0.10) and WET-S ( = 0.07). At a moderately high (25% DM) inclusion, blending C/S or feeding WET-S resulted in cattle growth performance and carcass characteristics similar to those of CTL and corn-based coproducts. PMID- 26812331 TI - Estimation of the indigestible fiber in different forage types. AB - The role of indigestible NDF is essential in relation to OM digestibility prediction, total tract digestibility, rumen fill, passage rate, and digestion kinetics. Moreover, the truly indigestible NDF (iNDF) represents a core point in dynamic models used for diet formulations. However, despite its wide possible applications, few trials have been conducted to quantify iNDF and even fewer to investigate whether or not it is consistent among different forage sources. The objective of this study was to predict the iNDF by measuring the residual NDF after 240-h in vitro fermentation to determine the unavailable NDF (uNDF) within and among various forage types. Finally, a mathematical approach was investigated for the estimation of the uNDF fraction. In all, 688 forages were analyzed in this study. This pool included 122 alfalfa hays, 282 corn silages, and 284 grass hays. Values of uNDF varied among different forages and within the same type (22.7% +/- 4.48%, 20.1% +/- 4.23%, and 11.8% +/- 3.5% DM for grass hay, alfalfa hay, and corn silages, respectively). The relationship among uNDF and ADL was not constant and, for grass hay and corn silage, was different ( 0.05) from the 2.4 * lignin value applied by the traditional Chandler equation. The observed uNDF:ADL ratio was 3.22 for grass hay and 3.11 for corn silage. Relationships among chemical and biological parameters and uNDF were investigated via simple and multiple regression equations. The greatest correlation with a single variable was obtained by ADL and ADF when applied to the whole data set ( = 0.63). Greater coefficients of determination resulted from a multiple regression equation for the whole data set ( = 0.80) and within each forage type ( = 0.65, 0.77, and 0.54 for grass hay, alfalfa hay, and corn silage, respectively). In conclusion, a regression approach requires specific equations and different regression coefficients for each forage type. The direct measurement of uNDF represented the best approach to obtain an accurate prediction of the iNDF and to optimize its specific purpose in dynamic nutrition models. PMID- 26812330 TI - Supplementation of corn dried distillers grains plus solubles to gestating beef cows fed low-quality forage: I. Altered intake behavior, body condition, and reproduction. AB - To investigate the effects of corn dried distillers grains plus solubles (DDGS) supplementation to cows fed corn stover and silage during late gestation, 27 multiparous beef cows (674 +/- 17 kg; BCS, 5.6 +/- 0.1) were divided randomly into 2 pens equipped with electronic feeders. For 10 wk, both groups were fed the basal diet for ad libitum intake while 1 group was supplemented (SUP; = 12) with DDGS at 0.3% of BW (DM basis). Following parturition, all cows received the same diet for an additional 8 wk. During gestation, SUP cows gained BW ( < 0.01), and there was no change in BCS ( 0.79). Nonsupplemented (CON) cows tended to lose BW ( 0.06) and lost BCS ( < 0.01) during gestation. Supplemented cows consumed more forage ( 0.01) and total feed than CON cows. An interaction of treatment and day was observed for time spent consuming forage ( < 0.01); SUP cows consumed forage faster than CON cows ( <= 0.01) early in gestation. Control cows ate more meals than SUP cows ( = 0.06) from d 201 to 218 of gestation. Supplemented cows tended ( = 0.09) to consume larger meals than CON cows and spent more ( < 0.01) time eating than CON cows around d 240 of gestation. Calves born to SUP cows tended ( = 0.06) to be heavier than calves born to CON cows. During lactation, both groups gained ( < 0.01) BW. Body condition score was less ( < 0.05) in CON cows than it was in SUP cows at the end of the study. Dry matter intake during lactation increased ( < 0.01) over time but was not influenced ( = 0.44) by treatment. Supplemented cows spent more time ( < 0.01) eating than CON cows after wk 4 of lactation, and they ate faster than CON cows until wk 3 of lactation whereas CON cows ate faster than SUP cows after wk 6 of lactation ( 0.01). The number of meals increased with advancing lactation ( < 0.01) and CON cows averaged more meals daily than SUP cows ( = 0.01). Conversely, meal size decreased as lactation advanced ( < 0.01), and SUP cows consumed larger meals than CON cows ( = 0.05). Supplementation with DDGS during gestation influenced intake behavior during gestation and lactation as well as the maintenance of maternal BW and BCS and calf birth BW. PMID- 26812332 TI - Effect of a lysine depletion-repletion protocol on the compensatory growth of growing-finishing pigs. AB - The effect of Lys restriction followed by a repletion period on the performance of growing pigs was studied during 3 feeding phases, each lasting 28 d. A total of 47 castrated male pigs (G Performer 8.0 * Fertilis 25 pigs; Genetiporc Inc., Saint-Bernard, QC, Canada; initial BW of 26.7 +/- 2.7 kg) were given each d 70% or 100% of their Lys requirements according to 1 of the following 5 sequences: 70 70-70, 70-70-100, 70-100-70, 70-100-100, or 100-100-100 (for each sequence, numbers indicate the Lys supply percentage in phase 1, 2, and 3, respectively). Individual Lys requirements were estimated daily on the basis of each pig's actual BW and feed intake and BW gain patterns obtained by regression using each pig's historical data. At the end of phase 1, the pigs given 100% of their Lys requirements had higher ADFI ( = 0.01), ADG ( < 0.01), and average daily protein deposition ( < 0.01) than did the pigs given 70% of their requirements. Similar results were observed during phases 2 and 3. At the end of phase 2, the pigs in the 70-100 sequence did not display any compensatory response, given that their ADFI, ADG, and average daily protein deposition did not differ from those of the pigs in the 100-100 sequence. Similar results were observed during phase 3. Although no compensatory growth was observed during the growing phases, the fact that the pigs in the 70-100-100 treatment were able to catch up in terms of BW and body protein mass to the pigs in the 100-100-100 sequence could indicate that a small degree of compensation did occur; these research results cannot ascertain that any compensatory growth occurred. PMID- 26812333 TI - Evaluation of isoquinoline alkaloid supplementation levels on ruminal fermentation, characteristics of digestion, and microbial protein synthesis in steers fed a high-energy diet. AB - Four Holstein steers with ruminal and duodenal cannulas were used in a 4 * 4 Latin square design to examine the effect of daily intake of 0, 2, 4 or 6 g/steer of standardized plant extract containing a mixture of quaternary benzophenanthridine alkaloids and protopine alkaloids (QBA+PA) on the characteristics of ruminal fermentation and characteristics of digestion. The basal diet consisted of a steam-flaked corn-based finishing diet that contained 62% corn and 12% sudangrass hay and the rest of diet was composed of mainly dried distillers grains, molasses, fat, and minerals. The source of QBA+PA used was Sangrovit-RS (Phytobiotics Futterzusatzstoffe GmbH, Eltville, Germany) and supplementation levels of 2, 4, and 6 g Sangrovit-RS?steer?d, which represented a net daily ingestion of approximately 6, 12, and 18 mg of QBA+PA compounds, respectively. Inclusion of QBA+PA linearly increased ( = 0.04) flow to the duodenum of nonammonia N and linearly decreased ( < 0.01) duodenal flows of ammonia N. Ruminal microbial efficiency (duodenal microbial N; g/kg OM fermented in the rumen) and protein efficiency (duodenal nonammonia N; g/g N intake) were increased ( < 0.05) as the level of QBA+PA increased. There were no effects of QBA+PA supplementation on ruminal, postruminal, and total tract digestion of OM, starch, and NDF, but postruminal and total tract digestion of N increased ( < 0.01) as the level of QBA+PA increased. Digestible energy of the diet tended to increase (linear affect, = 0.09) with QBA+PA supplementation. Ruminal pH and total VFA molar concentrations were not different between treatments. Ruminal NH N concentration linearly decreased ( = 0.02) with QBA+PA supplementation. Ruminal molar proportion of acetate increased ( = 0.04) as the supplementation level of QBA+PA increased. It is concluded that QBA+PA supplementation enhances efficiency of N utilization in feedlot steers fed a steam-flaked corn-based finishing diet. This effect was due, in part, to enhanced ruminal microbial efficiency, decreased ruminal degradation of dietary nonammonia N, and enhanced postruminal N digestion. PMID- 26812334 TI - Relationship of glucocorticoids and hematological measures with feed intake, growth, and efficiency of finishing beef cattle. AB - The objective of this experiment was to determine the association of glucocorticoids and markers for immune status in finishing beef steers and heifers with DMI, growth, and efficiency. Steers ( = 127) and heifers ( = 109) were individually fed a finishing ration for 84 d with BW measured every 21 d. Blood samples were collected via jugular venipuncture for metabolite (glucose and lactate) and cortisol analysis and rectal grab samples of feces were collected for corticosterone analysis on d 83 of the experiment. Plasma cortisol was not correlated to DMI ( = -0.08, > 0.05) or fractional DMI (g DMI/kg BW; = -0.03, > 0.05) but was negatively correlated with ADG ( = -0.17, < 0.01) and G:F ( = 0.20, < 0.01) and positively correlated to residual feed intake (RFI; = 0.14, < 0.05). Fecal corticosterone was positively correlated to fractional DMI ( = 0.15, < 0.05) and RFI ( = 0.23, < 0.01) and negatively correlated to G:F ( = -0.18, < 0.01). Using a mixed model analysis, none of the metabolites or hormones were associated with DMI ( > 0.05) but fecal corticosterone was positively associated with fractional DMI only in heifers ( = 0.04). Plasma lactate ( < 0.01) was and plasma cortisol ( < 0.10) tended to be negatively associated with ADG. Plasma cortisol ( < 0.05) and fecal corticosterone tended ( < 0.10) to be negatively associated with G:F. Fecal corticosterone was positively associated with RFI in heifers ( < 0.04). In a mixed model analysis, total leukocyte count was positively associated with ADG ( < 0.04) and tended to be positively associated with G:F ( < 0.06). Among leukocyte subtypes, neutrophil count was positively associated with ADG in steers ( < 0.02) and monocytes were positively associated with ADG in heifers ( < 0.03). Lymphocyte counts (LY) in steers were negatively associated with DMI ( = 0.03) and fractional DMI ( < 0.03). In heifers, LY tended to be positively associated with DMI ( < 0.09) and fractional DMI ( < 0.06). Lymphocyte count was also positively associated with ADG ( < 0.01) and G:F ( = 0.05) in heifers. The association of production traits with immune status seems to be different between steers and heifers. There was a stronger relationship of cortisol than fecal corticosterone to feed efficiency measures, suggesting that cortisol concentrations could be a better marker for feed efficiency traits than fecal corticosterone concentrations. PMID- 26812335 TI - Effect of abomasal carbohydrates and live yeast on measures of postruminal fermentation. AB - Two studies were conducted to evaluate the effects of abomasal carbohydrate infusion on nutrient digestibility and fecal measures. In Exp. 1, 5 Holstein steers were assigned to a Latin square with 1-wk periods and were abomasally infused on a single day at the end of each period with water alone, a single pulse dose of water with 1 g/kg BW oligofructose or cornstarch, or 4 pulse doses of water with 0.25 g/kg BW oligofructose or cornstarch administered every 6 h. Total tract nutrient digestibility was not affected by treatment except for a tendency for a decrease in starch digestibility in response to the 1 g/kg BW dose of cornstarch ( < 0.10). Compared with the control, both oligofructose and starch infusions caused similar decreases in fecal pH ( < 0.05) and increases in fecal short-chain fatty acids ( <= 0.01) measured 12 h after the first infusion, with the single 1 g/kg BW infusions causing a greater magnitude of pH change compared with the four 0.25-g/kg BW infusions ( < 0.01). All treatments increased concentration of fecal lipopolysaccharide compared with the control for at least 1 time point following the infusion ( < 0.05), with a greater increase observed for the 0.25 g/kg BW infusions of oligofructose compared with the other treatments ( < 0.05). Results of Exp. 1 indicate that both oligofructose and cornstarch infusions increased carbohydrate fermentation in the intestines and can be used as a method to evaluate the impact of excessive intestinal fermentation on intestinal health. In Exp. 2, 6 Holstein steers received abomasal pulse doses of 0 (control) or 10 g/d live var. (SB) according to a crossover design with 18-d periods. Abomasal infusions of 4 pulse doses of 0.25 g/kg BW oligofructose administered every 6 h were conducted on d 16 of each period. During the baseline period prior to the oligofructose challenge, there were no effects of SB on fecal measures except for an increase in apparent total tract NDF digestibility ( < 0.05), suggesting that SB increased intestinal fiber fermentation. During the oligofructose challenge, SB increased fecal score ( = 0.03) and tended to reduce fecal short-chain fatty acids ( = 0.10). Results of Exp. 2 suggest that abomasal SB modestly stabilized the intestinal environment during increased carbohydrate fermentation. PMID- 26812336 TI - Feeding wet distillers grains plus solubles with and without a direct-fed microbial to determine performance, carcass characteristics, and fecal shedding of O157:H7 in feedlot heifers. AB - The inclusion of wet distillers grains plus solubles (WDGS) in feedlot diets has become a common practice in many regions of the United States due to the expanded production of byproducts and fluctuating corn prices related to ethanol production and other factors. In addition, societal concerns over the continued use of antimicrobials in agriculture production combined with an enhanced interest in disease and pathogen prevention in the food supply have led to an increased interest in use of direct-fed microbials (DFM) in growing and finishing cattle. Direct-fed microbials have been shown to improve ADG and feed efficiency, alter ruminal fermentation, and decrease fecal shedding of potential harmful pathogens in feedlot cattle in some experiments. The objective of this experiment was to evaluate the effects of WDGS inclusion with or without a DFM containing (1 * 10 cfu ? heifer ? d) combined with (1 * 10 cfu ? heifer ? d) on the performance, carcass characteristics, and O157:H7 shedding in feedlot heifers. In early August, 288 crossbred heifers (initial BW = 295 +/- 28 kg) were assigned to 1 of 4 treatments (12 pens per treatment; 6 heifers per pen) in a randomized complete block design with a 2 * 2 factorial arrangement of treatments. Body weights and fecal grab samples were obtained at approximately 28-d intervals throughout the experiment. Across the feeding period, heifers fed 30% WDGS tended ( = 0.09) to have greater ADG and had greater carcass-adjusted ADG ( = 0.05) compared with heifers fed dry-rolled corn (DRC). Dry matter intake was not affected ( = 0.65) by diet, although carcass-adjusted G:F tended ( = 0.10) to be improved for heifers fed WDGS. Heifers fed 30% WDGS tended ( <= 0.10) to have greater fat thickness at the 12th rib, lower marbling scores, and higher yield grades. The inclusion of . combined with . in the diet had no effect ( > 0.10) on performance or carcass merit in the present experiment. The incidence of O157:H7 throughout the experiment was low, with only 18 positive samples across all sampling periods. Neither WDGS inclusion nor the inclusion of . combined with . in the diet had any effect ( > 0.10) on O157:H7 shedding in this experiment. Feeding 30% WDGS to feedlot heifers improved animal performance compared to the DRC-based control diet. PMID- 26812337 TI - A meta-analysis of lasalocid effects on rumen measures, beef and dairy performance, and carcass traits in cattle. AB - The effects of lasalocid on rumen measures, beef and dairy performance, and carcass traits were evaluated using meta-analysis. Meta-regression was used to investigate sources of heterogeneity. Ten studies (20 comparisons) were used in the meta-analysis on rumen measures. Lasalocid increased total VFA and ammonia concentrations by 6.46 and 1.44 m, respectively. Lasalocid increased propionate and decreased acetate and butyrate molar percentage (M%) by 4.62, 3.18, and 0.83%, respectively. Valerate M% and pH were not affected. Meta-regression found butyrate M% linearly increased with duration of lasalocid supplementation (DUR; = 0.017). When >200 mg/d was fed, propionate and valerate M% were higher and acetate M% was lower ( = 0.042, = 0.017, and = 0.005, respectively). Beef performance was assessed using 31 studies (67 comparisons). Lasalocid increased ADG by 40 g/d, improved feed-to-gain ratio (F:G) by 410 g/kg, and improved feed efficiency (FE; combined measure of G:F and the inverse of F:G). Lasalocid did not affect DMI, but heterogeneity in DMI was influenced by DUR ( = 0.004) and the linear effect of entry BW ( = 0.011). The combination of <=100 vs. >100 d DUR and entry BW <=275 vs. >275 kg showed that cattle <=275 kg at entry fed lasalocid for >100 d had the lowest DMI. Heterogeneity of ADG was influenced by the linear effect of entry BW ( = 0.028) but not DUR. Combining entry BW <=275 vs. >275 kg and DUR showed that cattle entering at >275 kg fed <=100 d had the highest ADG. The FE ( = 0.025) and F:G ( = 0.015) linearly improved with dose, and entry BW >275 kg improved F:G ( = 0.038). Fourteen studies (25 comparisons) were used to assess carcass traits. Lasalocid increased HCW by 4.73 kg but not dressing percentage, mean fat cover, or marbling score. Heterogeneity of carcass traits was low and not affected by DUR or dose. Seven studies (11 comparisons) were used to assess dairy performance but the study power was relatively low and the evidence base is limited. Lasalocid decreased DMI in total mixed ration-fed cows by 0.89 kg/d but had no effect on milk yield, milk components, or component yields. Dose linearly decreased DMI ( = 0.049). The DUR did not affect heterogeneity of dairy measures. This work showed that lasalocid improved ADG, HCW, FE, and F:G for beef production. These findings may reflect improved energy efficiency from increased propionate M% and decreased acetate and butyrate M%. Large dairy studies are required for further evaluation of effects of lasalocid on dairy performance. PMID- 26812338 TI - Microbial community profiles of the jejunum from steers differing in feed efficiency. AB - Research regarding the association between the microbial community and host feed efficiency in cattle has primarily focused on the rumen. However, the various microbial populations within the gastrointestinal tract as a whole are critical to the overall well-being of the host and need to be examined when determining the interplay between host and nonhost factors affecting feed efficiency. The objective of this study was to characterize the microbial communities of the jejunum among steers differing in feed efficiency. Within 2 contemporary groups of steers, individual ADFI and ADG were determined from animals fed the same diet. At the end of each feeding period, steers were ranked based on their standardized distance from the bivariate mean (ADG and ADFI). Four steers with the greatest deviation within each Cartesian quadrant were sampled ( = 16/group; 2 groups). Bacterial 16S rRNA gene amplicons were sequenced from the jejunum content using next-generation sequencing technology. The phylum Firmicutes accounted for up to 90% of the populations within all samples and was dominated by the families Clostridiaceae and Ruminococcaceae. UniFrac principal coordinate analyses did not indicate any separation of microbial communities within the jejunum based on feed efficiency phenotype, and no significant changes were indicated by bacterial diversity or richness metrics. The relative abundances of microbial populations and operational taxonomic units did reveal significant differences between feed efficiency groups ( < 0.05), including the phylum Proteobacteria ( = 0.030); the families Lachnospiraceae ( = 0.035), Coriobacteriaceae ( = 0.012), and Sphingomonadaceae ( = 0.035); and the genera ( = 0.019), ( = 0.018), and ( = 0.022). The study identified jejunal microbial associations with feed efficiency, ADG, and ADFI. This study suggests the association of the jejunum microbial community as a factor influencing feed efficiency at the 16S level. PMID- 26812339 TI - Effects of various roughage levels with whole flint corn grain on performance of finishing cattle. AB - Performance responses to steam flaking flint corn as well as to the addition of roughage to finishing diets composed of whole flint corn were evaluated. Ninety six Nellore bulls were stratified by initial BW (373 +/- 11 kg) and randomly allotted to 16 feedlot pens (6 bulls/pen) in a randomized complete block design with 4 replicates/treatment. Dietary treatments for the 86-d feeding trial consisted of (DM basis) 1) 78.8% steam-flaked flint corn with 6% sugarcane bagasse and 0.20% urea, 2) 85% whole flint corn without sugarcane bagasse, 3) 81.9% whole flint corn with 3% sugarcane bagasse and 0.10% urea, and 4) 78.8% whole flint corn with 6% sugarcane bagasse and 0.20% urea. All diets contained 15% (DM basis) of a pelleted protein, mineral, and vitamin supplement. Compared with whole flint corn grain, flaking of flint grain decreased ( < 0.01) DMI but did not alter ADG ( = 0.86), so G:F was increased ( = 0.02). Although steam flaking did not alter final BW and carcass characteristics ( > 0.47), it increased energy content of the diet ( < 0.03) and total tract starch digestibility ( < 0.01). In addition, flaking increased ( < 0.01) NEg of flint corn when compared with whole corn. Increasing the roughage content of WC-based diets resulted in quadratic ( < 0.02) responses in DMI, NEm and NEg intakes, ADG, and final BW but had no effect ( > 0.47) on G:F or on observed energy content of the diet. In summary, steam flaking of flint corn when fed in diets containing 6% sugarcane bagasse decreased DMI by 17% but increased G:F by 20% and NEg of corn calculated from feedlot performance by 23%; these responses markedly exceed those typically observed with dent corn grain. Moreover, adding 3% sugarcane bagasse to a flint whole corn grain diet optimized feedlot performance of Nellore bulls. PMID- 26812340 TI - Effect of dietary replacement of alfalfa with urea-treated almond hulls on intake, growth, digestibility, microbial nitrogen, nitrogen retention, ruminal fermentation, and blood parameters in fattening lambs. AB - The objective of this study was to assess the effect of dietary replacement of alfalfa with urea-treated almond hulls (UAH) on DM and nutrients intakes, growth performance, diet digestibility, microbial N supply (MNS), N retention, rumen fermentation parameters, and blood metabolites in fattening male Shall lambs (29.9 +/- 1.9 kg initial BW). Three diets, with equal ME and CP concentrations and a forage-to-concentrate ratio of 40 to 60, were formulated in which alfalfa was replaced by different levels (0, 200, or 400 g/kg of diet DM) of UAH. Experimental diets were randomly assigned to the 3 groups ( = 8/group) in a completely randomized design for a 74-d period (14 d for adaptation and 60 d for data collection). Diets were offered as a total mixed ration to ensure 10% orts. Dry matter and nutrients intakes, animal growth, diet digestibility, MNS, N retention, rumen fermentation parameters, and plasma metabolites were determined. The dietary substitution of UAH for alfalfa had no effects on DMI (linear, = 0.96; quadratic, = 0.86), ADG (linear, = 0.35; quadratic, = 0.19), and G:F (linear, = 0.66; quadratic, = 0.13). In vivo digestibility coefficients of DM (linear, = 0.82; quadratic, = 0.42), OM (linear, = 0.73; quadratic, = 0.95), CP (linear, = 0.24; quadratic, = 0.66), and ash-free NDF (linear, = 0.69; quadratic, = 0.74) were not affected by the dietary treatment. Feeding lambs on diets containing UAH instead of alfalfa had no effects on MNS (linear, = 0.63; quadratic, = 0.68) and N retention (linear, = 0.44; quadratic, = 0.17). Rumen pH (linear, = 0.26; quadratic, = 0.071), ammonia N (linear, = 0.39; quadratic, = 0.13), and VFA (linear, = 0.091; quadratic, = 0.86) concentrations, acetic acid to-propionic acid ratio (linear, = 0.93; quadratic, = 0.62), and protozoa population (linear, = 0.62; quadratic, = 0.22) were not influenced by the experimental diets. Substituting alfalfa with UAH had no effects on the plasma concentrations of glucose (linear, = 0.55; quadratic, = 0.91), triglycerides (linear, = 0.97; quadratic, = 0.44), cholesterol (linear, = 0.71; quadratic, = 0.70), urea N (linear, = 0.084; quadratic, = 0.12), total protein (linear, = 0.53; quadratic, = 0.96), albumin (linear, = 0.43; quadratic, = 0.39), and globulin (linear, = 0.39; quadratic, = 0.25). It is concluded that UAH can be fed to fattening Shall lambs as a total replacement (400 g/kg of diet DM) for alfalfa without negative effects on animal performance. This byproduct can be a safe feedstuff to use in sheep diets and could help to reduce environmental pollution. PMID- 26812341 TI - Can the monitoring of animal welfare parameters predict pork meat quality variation through the supply chain (from farm to slaughter)? AB - The objective of this study was to assess the relationship between the animal welfare conditions evaluated through the supply chain and pork quality variation. A total of 4,680 pigs from 12 farms-5 animal welfare improved raising system (AWIRS) and 7 conventional raising system (CON) farms-were assessed from farm to slaughter through a comprehensive audit protocol merging the European Welfare Quality, the Canadian Animal Care Assessment, and American Meat Institute audit guide criteria. At the abattoir, a subsample of 1,440 pigs (120 pigs/farm) was randomly chosen out of 24 loads (2 farms per wk) transported by 2 drivers (driver A and driver B) for the assessment of stunning effectiveness, carcass bruises, blood lactate levels, and meat quality traits. Meat quality was assessed in the longissimus lumborum (LL) muscle 24 h postmortem by measuring ultimate pH (pHu), color (L*, a*, and b*), and drip loss. Data were analyzed by the MIXED, GLIMMIX, and NAPAR1WAY procedures of SAS. Spearman correlations were calculated to determine the relationship between audit scores and meat quality traits. Better animal welfare conditions, as showed by greater final scores for good housing (GHo; = 0.001) and good health ( = 0.006) principles, were recorded at AWIRS farms. Pigs from AWIRS farms handled by driver B displayed a greater percentage of turning back ( = 0.01) and slips ( < 0.001) during unloading and a greater ( = 0.02) frequency of falls in the stunning chute. A greater ( = 0.02) reluctance to move at loading was found in CON pigs loaded by driver A compared with driver B, whereas a greater ( < 0.001) reluctance to move was found in these pigs at unloading when they were unloaded by driver B. Drip loss was higher ( = 0.003) and pale, soft, and exudative pork percentage was greater ( < 0.001) in the LL muscle of the heavier AWIRS pigs. The GHO principle was best correlated with pHu ( = -0.75, = 0.01) and Minolta L* value ( = 0.87, < 0.001) of the LL muscle. Overall, drip loss variation in the LL muscle was correlated with the frequency of slips at unloading ( = 0.63, = 0.001) and in the restrainer area ( = 0.74, < 0.001). The results of this study showed that the quality of the raising system and truck driver skills as assessed by animal welfare audit protocols are important sources of variation in the behavioral response of pigs to preslaughter handling and may affect pork quality variation. However, the different live weight between CON and AWIRS pigs may have biased the meat quality results in this study. PMID- 26812342 TI - High environmental temperature around farrowing induced heat stress in crated sows. AB - The aim of the experiment was to study the impact of high ambient temperature (25 degrees C) around farrowing on crated sows unable to perform thermoregulatory behavior. Twenty sows were housed in 2 farrowing rooms in conventional farrowing crates. In 1 room (CONTROL) temperature was kept at 20 degrees C. In the other room (HEAT) temperature was initially kept at 20 degrees C and gradually raised until it reached 25 degrees C from d 112 to 115 of gestation. Then the temperature was gradually lowered to 20 degrees C. Sows were continuously video recorded for behavior recording. Sows' respiration rates were recorded from d 3 before farrowing to d 5 after farrowing. Sows' rectal temperatures were recorded from d 1 before farrowing to d 8 after farrowing, and sows' udder surface temperatures were recorded from the day of farrowing to d 3 after farrowing. All measures were recorded daily. Sows' BW were recorded at d 108 of gestation and at weaning. Sows' back fat was recorded on farrowing day, when room temperature was set again at 20 degrees C, and at weaning. Piglets were weighed at d 1, 14, and 21. The HEAT sows spent a higher proportion of time lying in the lateral position than CONTROL sows, both during the 16 h before farrowing and the 24 h after the start of farrowing ( < 0.05), but with no difference in the amount of time spent lying down between groups ( > 0.10). The HEAT sows had higher rectal temperature on d 1 after farrowing ( < 0.05) and had udder surface temperature 0.9 degrees C higher than that of CONTROL sows during the recording period ( < 0.05). The HEAT sows also tended to have longer farrowing duration ( < 0.10). Respiration rate was higher in HEAT sows on d 1 before farrowing and on the day of farrowing. On d 7, 8, and 9, CONTROL sows had higher feed intake ( < 0.05), and piglets from CONTROL sows were heavier at d 21 after farrowing ( < 0.05). High ambient temperature around farrowing altered sows' postural behavior. Sows reacted to the thermal challenge with higher respiration rate around farrowing, but both their rectal and udder temperatures were elevated, indicating that they were not able to compensate for the higher ambient temperature. High ambient temperature negatively influenced sows' feed intake, with negative impact on piglets' weaning weight. High temperatures around farrowing (25 degrees C) compromise crated sows' welfare, with a potential negative impact on offspring performance. PMID- 26812343 TI - Group and individual sow behavior is altered in early gestation by space allowance in the days immediately following grouping. AB - Aggression between domestic sows is greatest when sows are first introduced to each other and hierarchies form. The aim of this study was to determine the effect of a spacious "mixing pen" on sow aggression and stress. Sows were mixed into groups of 6 and allowed 2 (LOW; 8 groups and 48 sows), 4 (MED; 7 groups and 42 sows), or 6 m/sow (HIGH; 7 groups and 42 sows) for 4 d after mixing, at which point all pens were equalized to 2 m/sow. Salivary cortisol concentration and injury counts were measured on d -1, 0, 1, 3, and 4 relative to mixing, and behavior was also recorded on each of these days following mixing. Reproductive performance was assessed at farrowing. A linear mixed model was applied to the data. Data are presented as least squares means and standard error of the mean. Where transformations occurred, nontransformed adjusted means are presented in parentheses following the presentation of transformed data. In the primary analyses where measures were considered at the pen level, there were no effect of space allowance on fight number per sow, duration of fights, percentage of total time spent fighting, displacements, bites, knocks, and lunges ( > 0.05). These measures were higher on d 0 (i.e., fight number 1.0 +/- 0.1 [13.8]) compared with d 1 (0.4 +/- 0.1 [4.2]), 3 (0.7 +/- 0.1 [5.3]), and 4 (0.7 +/- 0.1 [5.5]; < 0.05), with no increase in aggression on d 4 when pen sizes were standardized ( > 0.05). There was increased percentage of time spent active (1.5 +/- 0.02 [33.7] for LOW, 1.5 +/- 0.02 [36.5] for MED, and 1.6 +/- 0.02 [43.4] for HIGH) and time spent exploring (1.8 +/- 0.1 [3.5] for LOW, 2.0 +/- 0.1 [4.0] for MED, and 2.3 +/ 0.1 [5.7] for HIGH) and number of nonaggressive sow-sow contacts (0.3 +/- 0.09 [2.2] for LOW, 0.4 +/- 0.07 [3.2] for MED, and 0.5 +/- 0.07 [4.5] for HIGH) in HIGH compared with LOW ( < 0.05). Farrowing rate and total piglets born were not affected by treatment ( > 0.05). A secondary analysis was conducted that examined individual sow behavior within each pen, and this identified increased injury number in the lowest ranked sows (involved in no fights on d 0 and no displacements on d0 to d4) in LOW (9.3 +/- 1.2 [107.9] for LOW, 6.2 +/- 0.8 [53.0] for MED, and 5.1 +/- 0.8 [28.1] for HIGH) and also decreased fight number and duration in HIGH compared with LOW on d 0 and 1 ( < 0.05). Our primary data analysis demonstrates positive exploratory and social behaviors with increased space and suggests that a reduction in space following hierarchy formation is not a significant stressor. Additionally, there is some evidence at an individual sow level that increased space at mixing benefits sow welfare parameters, especially for low-ranked sows. PMID- 26812344 TI - Sources of variation in udder morphology of sows. AB - This experiment investigated the sources of variation in sow udder morphology. A cross-sectional study of 218 sows (109 Large White * Landrace [LWL] and 109 Meidam [Large White * Meishan {MDM}]) of different parities was conducted using a combination of scores and metric measurements. For each teat, 4 measures were taken: the inter-teat distance within the same row (SAMER), the distance from the base of the teat in the upper row to the abdominal midline (AML), the length of the teat from the tip to the base (LEN), and the diameter at the tip of the teat (DIA). Scores were adopted to define teat orientation (0 = teat not orientated perpendicular to the mammary gland and 1 = teat orientated perpendicular to the mammary gland), teat functionality (1 = milk channel not working, including teats that were blind, inverted, or very damaged; 2 = reduced availability of colostrum; and 3 = perfectly functional), and udder development (1 = not developed to 3 = fully developed). A longitudinal study on a subset of sows ( = 70) investigated how udder morphology changed in consecutive parities. Meidam had shorter teats, which were closer to the abdominal midline than LWL (LEN, < 0.001; AML, < 0.001). In both studies, first and second parity sows had smaller teats (LEN, < 0.001; DIA, < 0.001) than older multiparous sows. Teat position had a significant ( < 0.001) effect on SAMER in both breeds, with less distance between middle teat pairs. The distance from the base of the teats in the upper row to the abdominal midline was shorter in the anterior and posterior teats compared with the middle teat pairs. Teat length was greater in the anterior and middle teats than in the posterior ones, whereas DIA was greater in the middle teats. Teat pair position was associated with teat orientation ( < 0.001) and teat functionality ( < 0.001). Parity was associated with udder development ( < 0.001). Breed, parity, and teat pair position were all significant sources of variation in udder morphology in sows. PMID- 26812345 TI - Effects of vaccination against foot-and-mouth disease virus on reproductive performance of beef cows. AB - This study compared reproductive performance of cows vaccinated against the foot and-mouth disease (FMD) virus before timed AI or during early pregnancy (Exp. 1), as well as rectal temperature (RT) and plasma concentrations of the acute-phase protein haptoglobin in cattle vaccinated or not against the FMD virus (Exp. 2). Cattle utilized in Exp. 1 and 2 originated from herds with no historical occurrences of FMD and that received vaccination against the FMD virus biannually. In Exp. 1, 604 lactating, multiparous, nonpregnant Nelore cows were randomly assigned on d -31 of the experiment to receive 1) vaccination against the FMD virus on d >= 31 (VACPRE; = 291) and 2) vaccination against FMD virus on d 30 (VACGEST; = 313). From d -11 to 0, all cows were assigned to an estrus synchronization + timed AI (d 0) protocol. Pregnancy status to AI was verified on d 30 and 90 via transrectal ultrasonography. A treatment * day interaction was detected ( < 0.01) for pregnancy rates to AI, which were similar ( = 0.17) between VACPRE and VACGEST on d 30 (61.8% vs. 56.2%, respectively; SEM = 2.8) but greater ( < 0.01) for VACPRE on d 90 (59.4% vs. 46.9%, respectively; SEM = 2.8). Pregnancy loss from d 30 to 90 was greater ( < 0.01) in VACGEST compared with VACPRE (16.5% vs. 3.9%, respectively; SEM = 2.2). In Exp. 2, 40 pregnant Nelore females (20 nulliparous and 20 multiparous cows; BCS = 4.73 +/- 0.12) were ranked by parity and assigned to receive (VAC; = 20) or not receive (NOVAC; = 20) vaccination against the FMD virus. Blood samples were collected and RT was recorded before (h 0) and 24, 72, 120, and 168 h after treatment administration. Treatment * day interactions were detected ( < 0.01) for RT and plasma haptoglobin. The RT was greater ( < 0.01) in VAC compared with NOVAC at 24 h after treatment administration and was similar ( >= 0.31) between treatments at all other sampling hours. Plasma haptoglobin concentration was similar ( = 0.98) between VAC and NOVAC before treatment administration ( = 0.48) and greater ( < 0.01) in VAC at 24, 72, 120, and 168 h after treatment administration. In summary, vaccinating beef cows against the FMD virus resulted in a 4-fold increase in pregnancy loss when the vaccine was administered 30 d after timed AI compared with 31 d before timed AI. These outcomes can be associated with inflammatory and acute-phase reactions elicited by the FMD vaccine, which are known to impair pregnancy maintenance in cattle. PMID- 26812347 TI - Effect of extended postmortem aging and steak location on myofibrillar protein degradation and Warner-Bratzler shear force of beef M. semitendinosus steaks. AB - The objective of this study was to evaluate the effect of steak location and postmortem aging on cooked meat tenderness and myofibrillar protein degradation of steaks from M. semitendinosus (ST). Following harvest and a 6 d chill period, the left ST was removed from carcasses of crossbred feedlot steers ( = 60, average hot carcass weight 427 +/- 24 kg). Each ST was fabricated into ten 2.54 cm thick steaks originating from the proximal to distal end of the muscle. Steaks cut adjacent to each other were paired, vacuum packaged, and randomly assigned to 7, 14, 21, 42, or 70 d of aging at 2 +/- 1 degrees C. After aging, within each steak pair, steaks were randomly assigned to Warner-Bratzler shear force or myofibrillar proteolysis analysis (calpain activity and desmin and troponin-T degradation). Muscle fiber type and size were also determined at the 2 ends of the muscle. There was no location * d of aging interaction ( = 0.25) for ST steak WBSF. Steak location affected (quadratic, < 0.01) WBSF. As steaks were fabricated from the proximal to distal end, WBSF values decreased toward the middle of the muscle and then increased toward the distal end. Activity of all calpains and myofibrillar protein proteolysis were unaffected by steak location ( > 0.13). Type I, IIA, and IIX muscle fibers were larger at the proximal end of the muscle than the distal end ( < 0.01). Increasing d of aging improved WBSF (quadratic, < 0.01) for the duration of the 70 d postmortem period. As d of aging increased, intact calpain-1 activity decreased (quadratic, < 0.01) with activity detected through 42 d. Day of aging affected autolyzed calpain-1 (linear, < 0.01) and calpain-2 activity (quadratic, < 0.01). Through d 70 of aging, the intensity of intact 55 kDa desmin band decreased (linear, < 0.01), while there was an increase (linear, < 0.01) in the degraded 38 kDa band. Similarly, d of aging increased troponin-T proteolysis, indicated by a decrease (quadratic, < 0.01) in intensity of the intact 40 kDa band and an increase (linear, < 0.01) in the 30 kDa degraded band. Intramuscular WBSF differences are not due to proteolytic activity or myofibrillar degradation and seem related to muscle fiber size. The improvement of ST steak WBSF through 70 d of aging is partly due to continued degradation of desmin and troponin-T. Calpain proteolytic analysis indicates that autolyzed calpain-1 and calpain-2 may be involved in extended postmortem myofibrillar protein proteolysis. PMID- 26812346 TI - Impacts of meloxicam administration before temporary calf weaning on physiological and reproductive responses of beef cows. AB - The objective of this experiment was to evaluate temperament, physiological, and reproductive variables in beef cows assigned to an estrus synchronization + timed AI protocol including eCG administration, 48-h temporary calf weaning (TCW), or TCW + meloxicam administration. A total of 943 lactating, multiparous, nonpregnant Nelore cows, allocated into 8 groups of approximately 120 cows each, were assigned to the experiment. Groups were maintained in individual pastures and assigned to the following estrus synchronization + timed AI protocol: a 2-mg injection of estradiol benzoate and an intravaginal progesterone-releasing device (CIDR) on d 0, a 12.5-mg injection of PGF on d 7, CIDR removal in addition to a 0.6-mg injection of estradiol cypionate on d 9, and timed AI on d 11. Within each group, cows were randomly assigned on d 9 to 1) TCW from d 9 to 11 (TCW-CON; = 317), 2) no TCW and a 300-IU injection of eCG on d 9 (NOTCW; = 311), and 3) TCW CON in addition to meloxicam administration (intramuscular; 0.5 mg/kg BW) on d 9 (TCW-MEL; = 315). Cow BW and BCS were assessed on d 0. On d 9 and 11, blood samples were collected, and cow temperament was evaluated via chute score and exit velocity. Pregnancy status was verified 30 d after timed AI via transrectal ultrasonography. No treatment differences were detected ( >= 0.23) for cow age, days postpartum, BW, and BCS on d 0 of the estrus synchronization + timed AI protocol. No treatment effects were detected ( >= 0.41) for any of the temperament variables evaluated. A treatment * day interaction was detected ( = 0.02) for serum cortisol concentrations, which were similar ( = 0.55) between treatments on d 9 but greater ( <= 0.05) in TCW-CON and TCW-MEL compared with NOTCW cows on d 11. No treatment effects were detected ( = 0.90) for serum haptoglobin concentrations, which decreased from d 9 to 11 in all treatments (day effect; < 0.01). No treatment differences were detected ( = 0.84) for pregnancy rates to timed AI. In summary, TCW during estrus synchronization did not impact temperament or serum haptoglobin concentrations in beef cows but increased serum cortisol concentrations compared with cows not assigned to TCW, although such an outcome was not sufficient to impact pregnancy rates to timed AI. Moreover, administration of meloxicam did not alleviate the TCW-induced increase in serum cortisol concentrations and failed to benefit pregnancy rates to timed AI in beef cows. PMID- 26812348 TI - Bos indicus cattle possess greater basal concentrations of HSP27, alpha B crystallin, and HSP70 in skeletal muscle in vivo compared with cattle. AB - The objectives of the present study were to evaluate the basal concentrations of heat shock proteins (HSP) between and cattle and to determine if HSP basal concentrations change as an animal matures. A total of 40 cattle were used in a 2 * 2 factorial design to evaluate the effects of genotype and age (heifers and mature cows) on basal concentrations of heat shock protein 27 (HSP27), alpha B crystallin (Cryab), and heat shock protein 70 (HSP70). Each experimental group of 10 animals was sampled on a separate day over a period of 4 wk during July 2014. A muscle sample was collected from the longissimus thoracis (LT) and concentrations of HSP were quantified using ELISA. There were no significant differences in HSP concentration for the interaction between age and genotype or for age alone. cattle had greater ( < 0.05) basal concentrations of HSP27, Cryab, and HSP70 in the LT than cattle. The results of this study show that basal in vivo HSP concentrations differ between and cattle. However, further studies are needed to investigate the relationship between HSP concentrations and meat tenderness with respect to genotypes to see if HSP concentrations account for at least some variability in tenderness differences. PMID- 26812349 TI - Magnetization and Resistance Switchings Induced by Electric Field in Epitaxial Mn:ZnO/BiFeO3 Multiferroic Heterostructures at Room Temperature. AB - Electric field induced reversible switchings of the magnetization and resistance were achieved at room temperature in epitaxial Mn:ZnO(110)/BiFeO3(001) heterostructures. The observed modulation of magnetic moment is ~500% accompanying with a coercive field varying from 43 to 300 Oe and a resistive switching ratio up to ~10(4)% with the applied voltages of +/-4 V. The switching mechanisms in magnetization and resistance are attributed to the ferroelectric polarization reversal of the BiFeO3 layer under applied electric fields, combined with the reversible change of oxygen vacancy concentration at the Mn:ZnO/BiFeO3 interface. PMID- 26812350 TI - Some like it hot: The emerging role of spicy food (capsaicin) in autoimmune diseases. AB - Autoimmune diseases refer to a spectrum of diseases characterized by an active immune response against the host, which frequently involves increased autoantibody production. The pathogenesis of autoimmune diseases is multifactorial and the exploitation of novel effective treatment is urgent. Capsaicin is a nutritional factor, the active component of chili peppers, which is responsible for the pungent component of chili pepper. As a stimuli, capsaicin selectively activate transient receptor potential vanilloid subfamily 1(TRPV1) and exert various biological effects. This review discusses the effect of capsaicin through its receptor on the development and modulation of autoimmune diseases, which may shed light upon potential therapies in capsaicin-targeted approaches. PMID- 26812351 TI - Predicting the Maximum Earthquake Magnitude from Seismic Data in Israel and Its Neighboring Countries. AB - This paper explores several data mining and time series analysis methods for predicting the magnitude of the largest seismic event in the next year based on the previously recorded seismic events in the same region. The methods are evaluated on a catalog of 9,042 earthquake events, which took place between 01/01/1983 and 31/12/2010 in the area of Israel and its neighboring countries. The data was obtained from the Geophysical Institute of Israel. Each earthquake record in the catalog is associated with one of 33 seismic regions. The data was cleaned by removing foreshocks and aftershocks. In our study, we have focused on ten most active regions, which account for more than 80% of the total number of earthquakes in the area. The goal is to predict whether the maximum earthquake magnitude in the following year will exceed the median of maximum yearly magnitudes in the same region. Since the analyzed catalog includes only 28 years of complete data, the last five annual records of each region (referring to the years 2006-2010) are kept for testing while using the previous annual records for training. The predictive features are based on the Gutenberg-Richter Ratio as well as on some new seismic indicators based on the moving averages of the number of earthquakes in each area. The new predictive features prove to be much more useful than the indicators traditionally used in the earthquake prediction literature. The most accurate result (AUC = 0.698) is reached by the Multi Objective Info-Fuzzy Network (M-IFN) algorithm, which takes into account the association between two target variables: the number of earthquakes and the maximum earthquake magnitude during the same year. PMID- 26812352 TI - Dogs and Opossums Positive for Vaccinia Virus during Outbreak Affecting Cattle and Humans, Sao Paulo State, Brazil. AB - During a vaccinia virus (VACV) outbreak in Sao Paulo State, Brazil, blood samples were collected from cows, humans, other domestic animals, and wild mammals. Samples from 3 dogs and 3 opossums were positive for VACV by PCR. Results of gene sequencing yielded major questions regarding other mammalian species acting as reservoirs of VACV. PMID- 26812353 TI - Gate-Tunable Dirac Point of Molecular Doped Graphene. AB - Control of the type and density of charge carriers in graphene is essential for its implementation into various practical applications. Here, we demonstrate the gate-tunable doping effect of adsorbed piperidine on graphene. By gradually increasing the amount of adsorbed piperidine, the graphene doping level can be varied from p- to n-type, with the formation of p-n junctions for intermediate coverages. Moreover, the doping effect of the piperidine can be further tuned by the application of large negative back-gate voltages, which increase the doping level of graphene. In addition, the electronic properties of graphene are well preserved due to the noncovalent nature of the interaction between piperidine and graphene. This gate-tunable doping offers an easy, controllable, and nonintrusive method to alter the electronic structure of graphene. PMID- 26812354 TI - Louseborne Relapsing Fever among East African Refugees, Italy, 2015. AB - During June 9-September 30, 2015, five cases of louseborne relapsing fever were identified in Turin, Italy. All 5 cases were in young refugees from Somalia, 2 of whom had lived in Italy since 2011. Our report seems to confirm the possibility of local transmission of louse-borne relapsing fever. PMID- 26812356 TI - Knockdown of a putative insulin-like peptide gene LdILP2 in Leptinotarsa decemlineata by RNA interference impairs pupation and adult emergence. AB - Five insulin-like peptide LdILP genes were identified in Leptinotarsa decemlineata. All of them contained three exons and two introns, with three genes tandemly arrayed and well separated from the other two. Phylogenetic analysis revealed that the three LdILPs from three tandemly-arrayed genes grouped with TcILP1, whereas the other two resembled with TcILP2 and TcILP4 from Tribolium castaneum. Thus, the five LdILP genes were provisionally named LdILP1a, LdILP1b, LdILP1c, LdILP2 and LdILP4. LdILP2 was widely expressed in several tissues such as the brain-corpora cardiaca-corpora allata (BR-CC-CA) complex, gut and fat body. In contrast, LdILP1a and LdILP1b were only transcribed in BR-CC-CA, LdILP4 was in ovaries, and LdILP1c was in both BR-CC-CA and ovaries. Ingestion of double stranded RNAs (dsRNAs) targeting LdILP2 (dsLdILP2-1 and dsLdILP2-2) specifically knocked down LdILP2 and upregulated the transcription of both LdInR and Ld4EBP, indicating insulin/insulin-like growth factor signaling pathway (IIS) was inhibited. Approximately 50% of the LdILP2 RNAi larvae did not normally pupate and about 50% of the LdILP2 RNAi pupae did not emerge. Moreover, silencing LdILP2 reduced the expression of a juvenile hormone (JH) biosynthesis gene, lowered JH titer and disturbed JH signaling. Finally, knocking down LdILP2 inhibited an ecdysteroidogenesis gene, decreased 20-hydroxyecdysone (20E) titer, and repressed the expression of two 20E-response genes LdHR3 and LdFTZ-F1. Thus, the IIS pathway is involved in larval-pupal metamorphosis by modification of both JH and 20E signaling in L. decemlineata. PMID- 26812355 TI - RNA-sequencing study of peripheral blood monocytes in chronic periodontitis. AB - BACKGROUND: Monocytes are an important cell type in chronic periodontitis (CP) by interacting with oral bacteria and mediating host immune response. The aim of this study was to reveal new functional genes and pathways for CP at monocyte transcriptomic level. METHODS: We performed an RNA-sequencing (RNA-seq) study of peripheral blood monocytes (PBMs) in 5 non-smoking moderate to severe CP (case) individuals vs. 5 controls. We took advantage of a microarray study of periodontitis to support our findings. We also performed pathway-based analysis on the identified differentially expressed (DEx) transcripts/isoforms using DAVID (Database for Annotation, Visualization and Integrated Discovery). RESULTS: Through differential expression analyses at both whole gene (or whole non-coding RNA) and isoform levels, we identified 380 DEx transcripts and 5955 DEx isoforms with a PPEE (posterior probability of equal expression) of <0.05. Pervasive up regulation of transcripts at isoform level in CP vs. control individuals was observed, suggesting a more functionally active monocyte transcriptome for CP. By comparing with the microarray dataset, we identified several CP-associated novel genes (e.g., FACR and CUX1) that have functions to interact with invading microorganisms or enhance TNF production on lipopolysaccharide stimulation. DAVID analysis of both the RNA-seq and the microarray datasets leads to converging evidence supporting "endocytosis", "cytokine production" and "apoptosis" as significant biological processes in CP. CONCLUSIONS: As the first RNA-seq study of PBMs for CP, this study provided novel findings at both gene (e.g., FCAR and CUX1) and biological process level. The findings will contribute to better understanding of CP disease mechanisms. PMID- 26812357 TI - Effect of Antiepileptic Therapy on Serum 25(OH)D3 and 24,25(OH)2D3 Levels in Epileptic Children. AB - BACKGROUND: Vitamin D deficiency is not only associated with the adverse effects of chronic treatment with antiepileptic drugs (AEDs), but also with epilepsy. Although emerging evidence suggests that AEDs can accelerate the vitamin D catabolism, resulting in suboptimal vitamin D status, there are a limited number of studies examining the vitamin D status in epileptic patients, especially in first-episode or AEDs-naive children. METHODS: Determined with high-performance liquid chromatography-tandem mass spectrometry, circulating 25(OH)D3 and 24,25(OH)2D3 levels, and 24,25(OH)2D3:25(OH)D3 ratio were compared between AEDs treated epileptic (n = 363) and control (n = 159) children. To further figure out whether the patients were in a vitamin D deficient prone state even before treatment, epileptic children before their initiation of treatment (n = 51) were enrolled into a follow-up study. RESULTS: A significant decrease of 25(OH)D3 and 24,25(OH)2D3 levels, but a significant increase of 24,25(OH)2D3:25(OH)D3 ratio was observed in epileptic children, compared with controls. Baseline 25(OH)D3, 24,25(OH)2D3 and 24,25(OH)2D3:25(OH)D3 ratio in the follow-up group were similar to those in controls, but significantly changed with 2 months of AED therapy. CONCLUSIONS: Disturbed vitamin D levels were possibly the consequence of AED therapy, rather than the contributing factor of epilepsy. Collectively, circulating vitamin D levels should be monitored and corrected in AEDs-treated epileptic children. PMID- 26812358 TI - [The Ebola epidemic--few infected but many indirectly affected]. PMID- 26812359 TI - [Unbalanced criticism of the rehabilitation guarantee]. PMID- 26812360 TI - [Flawed report on screening for abdominal aortic aneurysm--redo!]. PMID- 26812361 TI - [Pain and symptom relief in child palliative care must become better]. PMID- 26812362 TI - [Adverse effects of screening have been weighed against the possible health benefits]. PMID- 26812363 TI - [Important with the right information about indoor environment for newly arrived]. PMID- 26812364 TI - Probing the Limits to MicroRNA-Mediated Control of Gene Expression. AB - According to the 'ceRNA hypothesis', microRNAs (miRNAs) may act as mediators of an effective positive interaction between long coding or non-coding RNA molecules, carrying significant potential implications for a variety of biological processes. Here, inspired by recent work providing a quantitative description of small regulatory elements as information-conveying channels, we characterize the effectiveness of miRNA-mediated regulation in terms of the optimal information flow achievable between modulator (transcription factors) and target nodes (long RNAs). Our findings show that, while a sufficiently large degree of target derepression is needed to activate miRNA-mediated transmission, (a) in case of differential mechanisms of complex processing and/or transcriptional capabilities, regulation by a post-transcriptional miRNA-channel can outperform that achieved through direct transcriptional control; moreover, (b) in the presence of large populations of weakly interacting miRNA molecules the extra noise coming from titration disappears, allowing the miRNA-channel to process information as effectively as the direct channel. These observations establish the limits of miRNA-mediated post-transcriptional cross-talk and suggest that, besides providing a degree of noise buffering, this type of control may be effectively employed in cells both as a failsafe mechanism and as a preferential fine tuner of gene expression, pointing to the specific situations in which each of these functionalities is maximized. PMID- 26812365 TI - Modulation of Hexadecyl-LPA-Mediated Activation of Mast Cells and Microglia by a Chemical Probe for LPA5. AB - Mast cells and microglia play a critical role in innate immunity and inflammation and can be activated by a wide range of endogenous and exogenous stimuli. Lysophosphatidic acid (LPA) has recently been reported to activate mast cells and microglia. Using the human mast cell line HMC-1 and the mouse microglia cell line BV-2, we show that LPA-mediated activation can be prevented by blockade of the LPA receptor 5 (LPA5) in both cell lines. The identification of new LPA5-specific antagonists as tool compounds to probe and modulate the LPA5/LPA axis in relevant in vitro and in vivo assays should contribute to better understanding of the underlying role of LPAs in the development and progression of (neuro-) inflammatory diseases. PMID- 26812366 TI - Diagnostic accuracy of lung ultrasound for interstitial lung disease in patients with connective tissue diseases: a meta-analysis. AB - OBJECTIVES: The purpose of this study was to evaluate and compare the diagnostic performance of lung ultrasound (US) in respect to high-resolution computed tomography (HRCT) findings in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). METHODS: We searched the Pubmed, Embase, and Cochrane Library databases, and performed a meta-analysis on the diagnostic accuracy of lung US according to B-lines (comet tail sign) and on the correlation coefficients between lung US scores and HRCT Warrick scores in CTD-ILD patients. RESULTS: Five studies that included a total of 349 patients were available for this meta-analysis. The pooled sensitivity and specificity of lung US were 91.5% (95% confidence interval [CI]: 84.5-96.0) and 81.3% (95% CI: 74.6-86.9), respectively. The positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 4.100 (2.133-7.879), 0.176 (0.006-0.363), and 34.73 (10.10-99.66), respectively. The area under the curve was 0.915 and the Q* index was 0.848, indicating a high diagnostic accuracy. When all four studies with systemic sclerosis were considered together, the pooled sensitivity and specificity of lung US were 89.5% (95% CI 80.3-95.3) and 79.6% (69.9-87.2), respectively. A significant correlation was found between lung US B-line scores and HRCT Warrick scores in CTD-ILD (correlation coefficient: 0.783; p-value <1 * 10-9). CONCLUSIONS: Our meta-analysis of published studies demonstrates that lung US has a high diagnostic accuracy, correlates well with HRCT findings, and plays an important role in the diagnosis of CTD-ILD. PMID- 26812367 TI - Calcinosis preferentially affects the thumb compared to other fingers in patients with systemic sclerosis. AB - OBJECTIVES: Although Raynaud's phenomenon often spares the thumb, clinical experience suggests conversely that, in patients with systemic sclerosis (SSc), the thumb is frequently affected by calcinosis (as is demonstrated on plain radiographs). Our aim was to investigate the hypothesis that, in patients with SSc, thumbs are more commonly affected by calcinosis than other digits. METHOD: Sixty-eight hand radiographs with at least one area of calcinosis were identified. Each digit on both hands of each patient was assigned a severity score on a scale from 0 to 3 (0 = no calcinosis, 3 = most severe). The scoring was completed twice, including and excluding the metacarpals. RESULTS: Right hands were found to be associated with slightly higher scores than left hands [estimate 0.14, 95% confidence interval (CI) 0.03-0.26]. Scores were lower for other fingers compared to thumbs. There was strong evidence (p < 0.0001) of a trend of decreasing severity moving from the thumb to the little finger. There was no evidence that the pattern of severity across the fingers was different on left and right hands (p = 0.77). The results were similar whether or not metacarpals were included. CONCLUSIONS: The thumb is affected by calcinosis more than other digits, followed by the index finger. This observation provides insight into the pathogenesis of SSc-related calcinosis, which may relate more to repetitive trauma than to ischaemia. PMID- 26812368 TI - Developing nitrosocarborane chemistry. AB - The new nitrosocarboranes [1-NO-2-R-1,2-closo-C2B10H10] [R = CH2Cl (1), CH3OCH2 (2) p-MeC6H4 (3), SiMe3 (4) and SiMe2tBu (5)] and [1-NO-7-Ph-1,7-closo-C2B10H10] (6) were synthesised by reaction of the appropriate lithiocarborane in diethyl ether with NOCl in petroleum ether followed by quenching the reaction with aqueous NaHCO3. These bright-blue compounds were characterised spectroscopically and, in several cases, crystallographically including structural determinations of 2 and 6 using crystals grown in situ on the diffractometer from liquid samples. In all cases the nitroso group bonds to the carborane as a 1e substituent (bent C-N-O sequence) and has little or no influence on , the weighted average 11B chemical shift, relative to that in the parent (monosubstituted) carborane. Mono- and dinitroso derivatives of 1,1'-bis(m carborane), compounds 7 and 8 respectively, were similarly synthesised but attempts to prepare the mononitroso 1,1'-bis(o-carborane) by the same protocol led only to the hydroxylamine species [1-(1'-1',2'-closo-C2B10H11)-2-N(H)OH-1,2 closo-C2B10H10] (9); the desired compound [1-(1'-1',2'-closo-C2B10H11)-2-NO-1,2 closo-C2B10H10] (10) was only realised by switching to a non-aqueous work-up. The involvement of water in effecting the net reduction of the NO function in 10 to N(H)OH in 9 was confirmed by a series of experiments involving [1-N(H)OH-2-Ph-1,2 closo-C2B10H10] (11), [1-(1'-2'-D-1',2'-closo-C2B10H10)-2-D-1,2-closo-C2B10H10] (12) and [1-(1'-2'-D-1',2'-closo-C2B10H10)-2-N(H)OH-1,2-closo-C2B10H10] (13). It is suggested that during aqueous work-up a water molecule, H-bonded to the acidic C2'H of 10, is "delivered" to the adjacent C2NO unit. The ability of the NO group in nitrosocarboranes to undergo Diels-Alder cycloaddition reactions with cyclic 1,3-dienes was established via the syntheses of [1-(NOC10H14)-1,2-closo-C2B10H11] (14) and [1-(NOC6H8)-2-Ph-1,2-closo-C2B10H10] (15). This strategy was then utilised to prepare derivatives of the elusive dinitroso compounds of [1,2-closo C2B10H12] and 1,1'-bis(o-carborane) leading to the sterically-crowded products [1,2-(NOC6H8)2-1,2-closo-C2B10H10] (16, prepared as meso and racemic diastereoisomers), [1-{1'-2'-(NOC6H8)-1',2'-closo-C2B10H10}-2-(NOC6H8)-1,2-closo C2B10H10] (17) and [1-(1'-1',2'-closo-C2B10H11)-2-(NOC6H8)-1,2-closo-C2B10H10] (18). PMID- 26812369 TI - The fate of H2O2 during managed aquifer recharge: A residual from advanced oxidation processes for drinking water production. AB - The fate of H2O2 residual from advanced oxidation process (AOP) preceding managed aquifer recharge (MAR) is of concern because H2O2 could lead to undesired effects on organisms in the MAR aquatic and soil ecosystem. The objective of this study was to distinguish between factors affecting H2O2 decomposition in MAR systems, simulated in batch reactors with synthetic MAR water and slow sand filter sand. The results showed that pure sand and soil organic matter had no considerable effect on H2O2 decomposition, whereas naturally occurring inorganic substances on the surface of sand grains and microbial biomass are the two main factors accelerating H2O2 decomposition in MAR systems. Additionally, the results showed that the H2O2 decompositions with different initial concentrations fitted first order kinetics in 2-6 h in a mixture of slow sand filter sand (as a substitute for sand from a MAR system) and synthetic MAR water with high bacterial population. An estimation indicated that low concentrations of H2O2 (<3 mg/L) could decompose to the provisional standard of 0.25 mg/L in the first centimeters of MAR systems with the influent water containing high microbial biomass 38 ng ATP/mL. PMID- 26812370 TI - Lead, mercury, and cadmium in umbilical cord serum and birth outcomes in Chinese fish consumers. AB - Heavy metals such as lead (Pb), mercury (Hg), and cadmium (Cd) were detected in the islands of Yangtze River estuary and Hangzhou bay and their exposure caused potential health risk for the residents. To assess the exposure levels of Pb, Hg, and Cd, the umbilical cord serum samples were collected from 103 mother-newborn pairs as the noninvasive specimens. The association of the concentration of Pb, Hg, and Cd with the birth outcomes was evaluated. Pb, Hg, and Cd had high exposure levels with the median concentrations at 76.20 MUg L(-1) [interquartile range (IQR): 44.71, 115.80], 21.94 MUg L(-1) (IQR: 15.10, 27.64), and 6.36 MUg L( 1) (IQR: 3.63, 13.34), respectively. A unit increase in the Pb umbilical cord serum concentration (MUg L(-1)) was significantly associated with a 0.29 cm (95% CI: -0.50, -0.09) decrease in birth height and a 0.22 cm (95%CI: -0.44, 0.00) decrease in head circumference. The middle tertile Pb and Hg exposure levels were found significantly negative effects on birth outcomes compared with low tertile exposure levels. Exposure to Cd showed no apparent effect on birth outcomes. Our results suggested that Pb and Hg exposure has potential adverse effects on birth outcomes in Chinese fish consumers from Yangtze River outlet and Hangzhou bay estuary regions. PMID- 26812371 TI - Response to: Letter to the Editor: "Cetacean mass stranding and multidisciplinary work". PMID- 26812372 TI - Attachment insecurity, mentalization and their relation to symptoms in eating disorder patients. AB - OBJECTIVE: To investigate the relationships of attachment security and mentalization with core and co-morbid symptoms in eating disorder patients. METHOD: We compared 51 eating disorder patients at the start of intensive treatment and 20 healthy controls on attachment, mentalization, eating disorder symptoms, depression, anxiety, personality disorders, psycho-neuroticism, autonomy problems and self-injurious behavior, using the Adult Attachment Interview, the SCID-I and II and several questionnaires. RESULTS: Compared with the controls, the eating disorder patients showed a higher prevalence of insecure attachment; eating disorder patients more often than controls received the AAI classification Unresolved for loss or abuse. They also had a lower level of mentalization and more autonomy problems. In the patient group eating disorder symptoms, depression, anxiety, psycho-neuroticism and autonomy problems were neither related to attachment security nor to mentalization; self-injurious behavior was associated with lesser attachment security and lower mentalization; borderline personality disorder was related to lower mentalization. In the control group no relations were found between attachment, mentalization and psychopathologic variables. DISCUSSION: Eating disorder patients' low level of mentalization suggests the usefulness of Mentalization Based Treatment techniques for eating disorder treatment, especially in case of self-injurious behavior and/or co-morbid borderline personality disorder. PMID- 26812373 TI - Association between Landscape Factors and Spatial Patterns of Plasmodium knowlesi Infections in Sabah, Malaysia. AB - The zoonotic malaria species Plasmodium knowlesi has become the main cause of human malaria in Malaysian Borneo. Deforestation and associated environmental and population changes have been hypothesized as main drivers of this apparent emergence. We gathered village-level data for P. knowlesi incidence for the districts of Kudat and Kota Marudu in Sabah state, Malaysia, for 2008-2012. We adjusted malaria records from routine reporting systems to reflect the diagnostic uncertainty of microscopy for P. knowlesi. We also developed negative binomial spatial autoregressive models to assess potential associations between P. knowlesi incidence and environmental variables derived from satellite-based remote-sensing data. Marked spatial heterogeneity in P. knowlesi incidence was observed, and village-level numbers of P. knowlesi cases were positively associated with forest cover and historical forest loss in surrounding areas. These results suggest the likelihood that deforestation and associated environmental changes are key drivers in P. knowlesi transmission in these areas. PMID- 26812374 TI - Creating a Continuously Learning Health System Through Technology: A Call to Action. PMID- 26812376 TI - Letter to the Editor. PMID- 26812377 TI - Application of Exploratory Factor Analysis and Item Response Theory to Validate the Genomic Nursing Concept Inventory. AB - BACKGROUND: Genomic nursing education requires an assessment to capture understanding of genetic-genomic concepts that are critical to competent nursing practice. The Genomic Nursing Concept Inventory (GNCI) was designed for that purpose. Advanced psychometric analyses were applied to GNCI responses to assess dimensionality and item and scale functioning and to inform inventory refinement. METHOD: The 31-item GNCI was administered to baccalaureate nursing students (N = 758), and exploratory factor analysis (EFA) was applied to explore scale dimensionality and construct validity. Item response theory was applied to explore individual item and overall scale functioning. RESULTS: Unidimensionality of the GNCI was supported. Internal consistency reliability was sufficient for the intended use of the scale. Although a few items were identified for review and potential revision, evidence supports GNCI score accuracy across a wide range of genomic knowledge ability. CONCLUSION: Validity evidence provided support for the use of GNCI scores for the intended purposes. PMID- 26812378 TI - Measure of Clinical Decision-Making Abilities of Nurse Practitioner Students. AB - BACKGROUND: This study reports the validity and reliability of using unfolding case studies to measure the clinical decision-making abilities of nurse practitioner students. METHOD: Two unfolding case studies were developed to assess students' ability to collect, interpret, and evaluate data. Content validity was assessed through percent agreement from three expert clinicians. Reliability was measured using Cronbach's alpha, test-retest, and interrater reliability. RESULTS: Fifty-two participants, primarily from family, acute care, and adult nurse practitioner programs, completed both unfolding cases. Content validation was nearly 100% for most items; other items were revised or deleted. A significant correlation was found between total mean scores at initial testing and at 1 month after both cases. High inter-rater reliability of the scored tool was noted, as measured with intraclass correlation coefficient. CONCLUSION: The use of case studies is a learner-centric method to measure the development and transition of clinical decision making. PMID- 26812379 TI - Impact of Service-Learning on Leadership and an Interest in Social Justice. AB - BACKGROUND: Many articles describe how service-learning has been implemented, but few studies have demonstrated its effectiveness. METHOD: A service-learning component was added to a course in a registered nurse-to-baccalaureate degree (RN to-BSN) completion program. The service-learning component included a 5-hour service requirement and class discussions. The purpose of this study was to evaluate service-learning's impact on postlicensure RN-to-BSN students' self evaluation of their leadership skills and their interest in social justice. This study used a quantitative, pretest-posttest control group design and a Likert scale survey. RESULTS: Variations in precourse and postcourse responses of the control group did not demonstrate a measurable effect; responses of the service learning group revealed a small effect size for both the leadership construct and the social justice construct. CONCLUSION: This study was unique in that it addressed nontraditional RN-to-BSN students in an accelerated program, 70% of whom were taking the course in an online format. PMID- 26812380 TI - Virtual TeamSTEPPS((r)) Simulations Produce Teamwork Attitude Changes Among Health Professions Students. AB - BACKGROUND: The majority of the estimated 400,000 or more patient deaths per year in the United States are from preventable medical errors due to poor communication. Team training programs have been established to teach teamwork skills to health professions students. However, it is often challenging to provide this training at a physical site. A brief intervention using a virtual learning environment with TeamSTEPPS((r))-based scenarios is described. METHOD: Using a pretest-posttest design, the effects on teamwork attitudes in 109 health professional students from two institutions and multiple disciplines were measured using the TeamSTEPPS Teamwork Attitudes questionnaire. RESULTS: Participants showed significant attitude changes in the categories of leadership, situation monitoring, mutual support, and communication (p ? .05), with significance in four of the six indicator attitudes in the communication section at the p ? .001 level. CONCLUSION: These findings indicate the potential impact that virtual learning experiences may have on teamwork attitudes in learners across professions on multiple campuses. PMID- 26812381 TI - Effects of Service-Learning on Graduate Nursing Students: Care and Advocacy for the Impoverished. AB - BACKGROUND: Service-learning is a widely used teaching method that appears to be a good fit for graduate nurses, with essential outcomes of advocacy and culturally responsive health care in special populations. However, quantitative evidence to support its effectiveness is minimal. This study evaluated the impact of service-learning on graduate nursing students' cultural competence, civic engagement, and knowledge and understanding of the effects of poverty on health care. Students are required to serve 16 to 20 hours in a nurse-run free clinic as part of their clinical experience. METHOD: Students (N = 152) completed pre- and postservice surveys. RESULTS: Statistically significant increases were noted in graduate students' civic engagement (p = .0001 to .0495), knowledge and understanding of health care issues (p < .0001), and in three of six statements related to cultural competence (p = .0001 to 9.662). Patient-reported outcomes and community impact is also positive. CONCLUSION: Service-learning appears to be an effective tool with graduate nurses. PMID- 26812382 TI - Preparing Students for Success on Examinations: Readiness Assurance Tests in a Graduate-Level Statistics Course. AB - BACKGROUND: Formative feedback is one way to foster students' readiness for statistics examinations. METHOD: The use of Readiness Assurance Tests was examined as an educational intervention in which feedback was provided for both correct and incorrect responses in a graduate-level statistics course. Examination scores in the intervention group (n = 56) were compared with those in a control group (n = 42). RESULTS: Intervention group examination scores significantly improved from 75.92 +/- 14.52 on the Readiness Assurance Test to 90.06 +/- 7.06, p < .001, on the midterm, and final examination scores improved from 78.23 +/- 17.29 to 85.6 +/- 6.98, p = .002. Intervention group midterm scores were significantly higher than those of the control group (90.06 +/- 7.06 versus 79.7 +/- 11.6, p < .001); however, no differences were found between the groups on the final examination (85.35 +/- 9.46 versus 85.6 +/- 6.98, p = .91). CONCLUSION: Use of Readiness Assurance Tests was an effective modality to increase student self-efficacy, learning experience, and, relative to a control group, midterm examination performance in statistics. PMID- 26812383 TI - Building Cultural Sensitivity and Interprofessional Collaboration Through a Study Abroad Experience. AB - BACKGROUND: Study abroad (SA) experiences for health professions students may be used to heighten cultural sensitivity to future patients and incorporate interprofessional education (IPE). METHOD: Two groups of nursing and pharmacy students participated in an SA elective over a 2-year period, traveling to China and India. RESULTS: Both groups improved significantly in knowledge, awareness, and skills following the travel experiences. Student reflections indicate that the SA experience was transformative, changing their views of travel, other cultures, personal environment, collaboration with other health professionals, and themselves. CONCLUSION: Use of SA programs is a novel method to encourage IPE, with a focus on enhancing the acquisition of cultural competency skills. PMID- 26812384 TI - Home Care Simulation to Teach Culturally Based Competencies in End-of-Life Care. AB - BACKGROUND: A simulation on end-of-life home care was developed for senior nursing students to address cultural components, communication skills, and common concerns at the end of life. Evidence-based clinical guidelines were provided beforehand on the treatment of pain, dyspnea, and depression, as well as culture, which affects attitudes and beliefs around end-of-life care. METHOD: The simulation of end-of-life care in a Chinese-American home was scripted with student actors to familiarize students with the concepts of death and dying, as well as integrating cultural considerations in providing such care. The scenario included recognizing traditions from the Chinese culture, including view's on dying in the home, spiritual beliefs, and the use of Eastern treatment remedies. RESULTS: After the simulation, many students reported that they had never reflected on death and dying before, and the majority of student and clinical faculty participants found that the simulation increased students' comfort level around end-of-life care. CONCLUSIONS: Students appreciated the family members' response, the importance of one's cultural views on death and dying, and the emotional impact of nursing care in these situations. PMID- 26812385 TI - An Innovative Approach to Staffing a Simulation Center in a College of Health Professions. AB - BACKGROUND: The current limited number of nurse faculty and available clinical sites requires innovative strategies to provide education to current and future nurses. Simulation centers and clinical education laboratories can meet this need, but staffing issues can be problematic. METHOD: This article describes how an urban university developed a cost-effective model to staff its clinical education laboratory. After two faculty members proposed a pilot program to fully integrate simulation into both the accelerated and traditional undergraduate nursing programs on two campuses, a need was identified for more nursing staff dedicated to the simulation program. RESULTS: Knowing that many recent nurse graduates were available while waiting to obtain their first nursing position, these new nurses were recruited to serve in a volunteer capacity, supporting nursing faculty in the simulation program. CONCLUSION: The new nurse graduate volunteer position quickly evolved into a paid nurse intern position and has proven to benefit students, faculty, and new nurse graduates. PMID- 26812386 TI - Use of a Mobile Device Simulation as a Preclass Active Learning Exercise. AB - BACKGROUND: Research shows that preclass activities introducing new material can increase student performance. In an effort to engage students in an active learning, preclass activity, the authors developed a mobile application. METHOD: Eighty-four nursing students were assigned a preclass reading exercise, whereas 32 students completed the preclass simulation scenario on their mobile device. All students completed the same electronic fetal monitoring (EFM) quiz 1 week following the lecture. The effects of reading or simulation on student quiz performance was evaluated with a student's paired t test, using an alpha of .05. RESULTS: Students completing the preclass simulation scored higher on the EFM quiz, compared with students assigned the preclass reading (85% versus 70% correct answers, p = .01). Student survey data indicated that the mobile device simulation was perceived as an engaging and desirable instructional tool. CONCLUSION: Nursing students completing the mobile device EFM preclass simulation outperformed the students who were given the traditional reading assignment. PMID- 26812387 TI - The FACTS: A Mnemonic for the Rapid Assessment of Rigor in Qualitative Research Studies. PMID- 26812388 TI - Multi-spin-state at a Li3PO4/LiCoO2 (104) interface. AB - We have found the disproportion between the intermediate spin (IS) and low spin (LS) configurations of Co atoms at a Li3PO4/LiCoO2 (104) interface through density functional molecular dynamics (DF-MD). The manifold of the spin state at the interface, however, does not affect the band alignment between the Li3PO4 and LiCoO2 regions. PMID- 26812389 TI - Synthesis, Photophysical and Electrochemical Properties, and Self-assembly Behavior of Two Hexaazatriphenylene Derivatives: A Single Bond Makes a Big Difference. AB - A hexaazatriphenylene (HAT) derivative (compound 1) that bears four n-octyl chains and two thienyl groups was designed and synthesized. Further light-induced oxidation coupling reaction led to thienyl-fused compound 2. Their photophysical and electrochemical properties and self-assembly behavior have been investigated by UV/Vis, fluorescence, and (1)H NMR spectroscopies, cyclic voltammetry (CV), scanning electron microscopy (SEM), and powder X-ray diffraction (PXRD). Although the difference in compounds 1 and 2 only lie in one single bond that connects the two thienyl segments, they displayed remarkably different properties, revealing an interesting structure-property relationship. PMID- 26812390 TI - Fully automated semi-quantitative toxicological screening in three biological matrices using turbulent flow chromatography/high resolution mass spectrometry. AB - BACKGROUND: In clinical and forensic toxicology, fast and specific methods are needed for the screening of different classes of drugs. A complete general unknown screening procedure was developed using turbulent flow chromatography with electrospray ionization and Orbitrap mass spectrometry. METHODS: After protein precipitation, samples were injected directly into the turbulent flow chromatographic system and analyzed with an Orbitrap mass spectrometer. The Exactive(r) operated in positive and negative modes with alternated high collision dissociation in order to obtain characteristic fragments. We built a library containing 616 compounds by analyzing a reference standard for all the molecules. RESULTS: Identification was based on retention time, accurate measured mass, isotopic pattern and presence of specific fragments. For each substance, we set a calibration range encompassing infra-therapeutic, therapeutic, supra therapeutic and toxic concentrations in order to generate semi-quantitative result. For 65% of the components, the limit of detection was below 5 ng/mL. The validation process showed the approach to be selective, sensitive, accurate and precise. CONCLUSION: The method has been accredited by COFRAC (French Accreditation Committee) according to the ISO 15189 standard. Applicability was successfully tested by analyzing authentic serum, urine and whole blood samples. PMID- 26812392 TI - Can Data Sharing Become the Path of Least Resistance? PMID- 26812391 TI - Birdsong Denoising Using Wavelets. AB - Automatic recording of birdsong is becoming the preferred way to monitor and quantify bird populations worldwide. Programmable recorders allow recordings to be obtained at all times of day and year for extended periods of time. Consequently, there is a critical need for robust automated birdsong recognition. One prominent obstacle to achieving this is low signal to noise ratio in unattended recordings. Field recordings are often very noisy: birdsong is only one component in a recording, which also includes noise from the environment (such as wind and rain), other animals (including insects), and human-related activities, as well as noise from the recorder itself. We describe a method of denoising using a combination of the wavelet packet decomposition and band-pass or low-pass filtering, and present experiments that demonstrate an order of magnitude improvement in noise reduction over natural noisy bird recordings. PMID- 26812393 TI - Cellulose Nanofibril Hydrogel Tubes as Sacrificial Templates for Freestanding Tubular Cell Constructs. AB - The merging of defined nanoscale building blocks with advanced additive manufacturing techniques is of eminent importance for the preparation of multiscale and highly functional materials with de novo designed hierarchical architectures. Here, we demonstrate that hydrogels of cellulose nanofibrils (CNF) can be processed into complex shapes, and used as a sacrificial template to prepare freestanding cell constructs. We showcase our approach for the fabrication of hollow fibers using a controlled extrusion through a circular die into a coagulation bath. The dimensions of the hollow fibers are tunable, and the final tubes combine the nanofibrillar porosity of the CNF hydrogel with a submillimeter wall thickness and centimeter-scale length provided by the additive manufacturing technique. We demonstrate that covalent and supramolecular cross linking of the CNFs can be used to tailor the mechanical properties of the hydrogel tubes within 1 order of magnitude and in an attractive range for the mechanosensation of cells. The resulting tubes are highly biocompatible and allow for the growth of mouse fibroblasts into confluent cell layers in their inner lumen. A detailed screening of several cellulases enables degradation of the scaffolding, temporary CNF hydrogel tube in a quick and highly cell-friendly way, and allows the isolation of coherent cell tubes. We foresee that the growing capabilities of hydrogel printing techniques in combination with the attractive features of CNFs-sustainable, globally abundant, biocompatible and enzymatically degradable-will allow making plant-based biomaterials with hierarchical structures and on-demand degradation useful, for instance, to engineer complex tissue structures to replace animal models, and for implants. PMID- 26812394 TI - Material Flow for the Intentional Use of Mercury in China. AB - Intentional use of mercury (Hg) is an important contributor to the release of Hg into the environment. This study presents the first inventory of material flow for intentional use of Hg in China. The total amount of Hg used in China increased from 803 +/- 95 tons in 2005 to its peak level of 1272 +/- 110 tons in 2011. Vinyl chloride monomer (VCM) production is the largest user of Hg, accounting for over 60% of the total demand. As regulations on Hg content in products are tightening globally against the background of the Minamata Convention, the total demand will decrease. Medical devices will likely still use a significant amount of Hg and become the second largest user of Hg if no proactive measures are taken. Significant knowledge gaps exist in China for catalyst recycling sector. Although more than half of the Hg used is recycled, this sector has not drawn enough attention. There are also more than 200 tons of Hg that had unknown fates in 2011; very little information exists related to this issue. Among the final environmental fates, landfill is the largest receiver of Hg, followed by air, water, and soil. PMID- 26812395 TI - Dynamical Effects and Product Distributions in Simulated CN + Methane Reactions. AB - Dynamics of collisions between structured molecular species quickly become complex as molecules become large. Reactions of methane with halogen and oxygen atoms serve as model systems for polyatomic molecule chemical dynamics, and replacing the atomic reagent with a diatomic radical affords further insights. A new, full-dimensional potential energy surface for collisions between CN + CH4 to form HCN + CH3 is developed and then used to perform quasi-classical simulations of the reaction. Coupled-cluster energies serve as input to an empirical valence bonding (EVB) model, which provides an analytical function for the surface. Efficient sampling permits simulation of velocity-map ion images and exploration of dynamics over a range of collision energies. Reaction populates HCN vibration, and energy partitioning changes with collision energy. The reaction cross-section depends on the orientation of the diatomic CN radical. A two-dimensional extension of the cone of acceptance for an atom in the line-of-centers model appropriately describes its reactivity. The simulation results foster future experiments and diatomic extensions to existing atomic models of chemical collisions and reaction dynamics. PMID- 26812396 TI - Editorial Comment. PMID- 26812397 TI - Critical Analysis of Forest Degradation in the Southern Eastern Ghats of India: Comparison of Satellite Imagery and Soil Quality Index. AB - India has one of the largest assemblages of tropical biodiversity, with its unique floristic composition of endemic species. However, current forest cover assessment is performed via satellite-based forest surveys, which have many limitations. The present study, which was performed in the Eastern Ghats, analysed the satellite-based inventory provided by forest surveys and inferred from the results that this process no longer provides adequate information for quantifying forest degradation in an empirical manner. The study analysed 21 soil properties and generated a forest soil quality index of the Eastern Ghats, using principal component analysis. Using matrix modules and geospatial technology, we compared the forest degradation status calculated from satellite-based forest surveys with the degradation status calculated from the forest soil quality index. The Forest Survey of India classified about 1.8% of the Eastern Ghats' total area as degraded forests and the remainder (98.2%) as open, dense, and very dense forests, whereas the soil quality index results found that about 42.4% of the total area is degraded, with the remainder (57.6%) being non-degraded. Our ground truth verification analyses indicate that the forest soil quality index along with the forest cover density data from the Forest Survey of India are ideal tools for evaluating forest degradation. PMID- 26812399 TI - Anthropogenic pollutants may increase the incidence of neurodegenerative disease in an aging population. AB - The current world population contains an ever-increasing increased proportion of the elderly. This is due to global improvements in medical care and access to such care. Thus, a growing incidence of age-related neurodegenerative disorders is to be expected. Increased longevity also allows more time for interaction with adverse environmental factors that have the potential exert a gradual pressure, facilitating the onset of organismic aging. Nearly all neurodegenerative disorders have a relatively minor genetic element and a larger idiopathic component. It is likely that some of the unknown factors promoting neurological disease involve the appearance of some deleterious aspects of senescence, elicited prematurely by low but pervasive levels of toxic materials present in the environment. This review considers the nature of such possible toxicants and how they may hasten neurosenescence. An enhanced rate of emergence of normal age related changes in the brain can lead to increased incidence of those specific neurological disorders where aging is an essential requirement. In addition, some xenobiotic agents appear to have the capability of engendering specific neurodegenerative disorders and some of these are also considered. PMID- 26812400 TI - Lysine Adduction by Reactive Metabolite(s) of Monocrotaline. AB - Pyrrolizidine alkaloids (PAs) are known hepatotoxins. The execution of the toxicities of the alkaloids requires metabolic activation. Protein modification by reactive metabolites of PAs has been suggested to be an important mechanism of the toxic actions of PAs. The objectives of the present study were to define the interactions of dehydromonocrotaline (DHM) with lysine, lysine derivatives, a model peptide, and bovine serum albumin and to explore the lysine modification of hepatic proteins of animals given monocrotaline. DHM was found to react with the epsilon-amino group of all model compounds tested after incubation with DHM, and the modification reaction preferentially occurred at C7 of the necine base. The lysine residue modification with the same regioselectivity was also observed in hepatic proteins of mice treated with monocrotaline. The observed modification increased with the increase in doses administered to the animals. This work allowed us to better understand the mechanisms of the hepatotoxicity of monocrotaline. PMID- 26812398 TI - N-Terminal Polypeptide of Annexin A2 Decreases Infection of Mycoplasma hyorhinis to Gastric Cancer Cells. AB - Mycoplasma infection in human and its contamination in cell cultures are worldwide problems. The drugs currently available for preventing or treating mycoplasma infection suffer from low sensitivity, strong resistance and high toxicity. Our previous work showed that Mycoplasma hyorhinis (M. hyorhinis) infection was mediated by the interaction between p37 of M. hyorhinis and Annexin A2 (ANXA2) of host cells, however the translational value of this mechanism was unknown. Herein, we synthesized the N-terminal of ANXA2 polypeptide (A2PP) and found that A2PP could decrease the infection of M. hyorhinis to gastric cancer cells and block M. hyorhinis infection-induced cell migration. Furthermore, we found that A2PP could reduce M. hyorhinis contamination of passage cells. Moreover, compared with the commercial antibiotics commonly used in cell culture to prevent M. hyorhinis infection, A2PP demonstrated a more effectiveness but a low toxicity on cell growth. Thus, our study for the first time revealed A2PP's potential for the treatment and prevention of M. hyorhinis infection. PMID- 26812401 TI - Breaking Down the Barriers in Complicated Pleural Sepsis. PMID- 26812403 TI - Winds of change in delivery of quality surgical care are not strong enough. PMID- 26812402 TI - The Phenazine 2-Hydroxy-Phenazine-1-Carboxylic Acid Promotes Extracellular DNA Release and Has Broad Transcriptomic Consequences in Pseudomonas chlororaphis 30 84. AB - Enhanced production of 2-hydroxy-phenazine-1-carboxylic acid (2-OH-PCA) by the biological control strain Pseudomonas chlororaphis 30-84 derivative 30-84O* was shown previously to promote cell adhesion and alter the three-dimensional structure of surface-attached biofilms compared to the wild type. The current study demonstrates that production of 2-OH-PCA promotes the release of extracellular DNA, which is correlated with the production of structured biofilm matrix. Moreover, the essential role of the extracellular DNA in maintaining the mass and structure of the 30-84 biofilm matrix is demonstrated. To better understand the role of different phenazines in biofilm matrix production and gene expression, transcriptomic analyses were conducted comparing gene expression patterns of populations of wild type, 30-84O* and a derivative of 30-84 producing only PCA (30-84PCA) to a phenazine defective mutant (30-84ZN) when grown in static cultures. RNA-Seq analyses identified a group of 802 genes that were differentially expressed by the phenazine producing derivatives compared to 30 84ZN, including 240 genes shared by the two 2-OH-PCA producing derivatives, the wild type and 30-84O*. A gene cluster encoding a bacteriophage-derived pyocin and its lysis cassette was upregulated in 2-OH-PCA producing derivatives. A holin encoded in this gene cluster was found to contribute to the release of eDNA in 30 84 biofilm matrices, demonstrating that the influence of 2-OH-PCA on eDNA production is due in part to cell autolysis as a result of pyocin production and release. The results expand the current understanding of the functions different phenazines play in the survival of bacteria in biofilm-forming communities. PMID- 26812405 TI - Working toward reducing postoperative fracture radiographs: a survey of Canadian surgeons. AB - BACKGROUND: When fracture management includes operative fixation with a load sharing construct in good-quality bone, screening for healing problems or hardware failure with radiographs in the first 6 postoperative weeks may be unnecessary. I sought to determine Canadian orthopedic surgeons' current protocol for early postoperative radiographs of stable, internally fixed fractures as well as their willingness to adopt a simplified protocol. METHODS: Members of the Canadian Orthopaedic Association were surveyed electronically. Five examples of surgically treated fractures were chosen to represent the spectrum of load sharing constructs. The survey collected demographic data and inquired about current postoperative radiograph protocols and consideration of a simplified protocol. RESULTS: Of the 822 emailed invitations to complete the survey, 400 were opened and 243 surveys were completed. Most participants (91%) practised in Canada and managed some trauma (91%), but were not trauma specialists (82%). Surgeon experience was equally distributed. Sixty-six percent of respondents acquire immediate postoperative radiographs after femur and tibia intramedullary nails, and 62% repeat radiographs at 2-week follow-up. Fifty-one percent of respondents acquire immediate postoperative radiographs after forearm, humerus and ankle internal fixation, and 69% repeat radiographs at 2-week follow-up. Of the respondents who currently acquire radiographs, 33% would consider foregoing immediate postoperative radiographs after intramedullary nailing of femur and tibia fractures, while 25% would forego them at 2-week follow-up. Similarly, 58% would consider foregoing radiographs immediately after internal fixation of forearm, humerus and ankle fractures, while 24% would forego them at 2-week follow-up. CONCLUSION: Many Canadian orthopedic surgeons do not acquire screening postoperative radiographs after stable fracture fixation, and many more are willing to adopt this practice. These findings support investigating the safety and cost-effectiveness of a simplified postoperative radiographic protocol. PMID- 26812406 TI - Discrepancy between gastroenterologists' and general surgeons' perspectives on repeat endoscopy in colorectal cancer. AB - BACKGROUND: A myriad of localization options are available to endoscopists for colorectal cancer (CRC); however, little is known about the use of such techniques and their relation to repeat endoscopy before CRC surgery. We examined the localization practices of gastroenterologists and compared their perceptions toward repeat endoscopy to those of general surgeons. METHODS: We distributed a survey to practising gastroenterologists through a provincial repository. Univariate analysis was performed using the chi2 test. RESULTS: Gastroenterologists (n = 69) reported using anatomical landmarks (91.3%), tattooing (82.6%) and image capture (73.9%) for tumour localization. The majority said they would tattoo lesions that could not be removed by colonoscopy (91.3%), high-risk polyps (95.7%) and large lesions (84.1%). They were equally likely to tattoo lesions planned for laparoscopic (91.3%) or open (88.4%) resection. Rectal lesions were less likely to be tattooed (20.3%) than left-sided (89.9%) or right sided (85.5%) lesions. Only 1.4% agreed that repeat endoscopy is the standard of care, whereas 38.9% (n = 68) of general surgeons agreed (p < 0.001). General surgeons were more likely to agree that an incomplete initial colonoscopy was an indication for repeat endoscopy (p = 0.040). Further, 56% of general surgeons indicated that the findings of repeat endoscopy often lead to changes in the operative plan. CONCLUSION: Discrepancies exist between gastroenterologists and general surgeons with regards to perceptions toward repeat endoscopy and its indications. This is especially significant given that repeat endoscopy often leads to change in surgical management. Further research is needed to formulate practice recommendations that guide the use of repeat endoscopy, tattoo localization and quality reporting. PMID- 26812407 TI - Trauma care and referral patterns in Rwanda: implications for trauma system development. AB - BACKGROUND: Trauma remains a leading cause of death worldwide. The development of trauma systems in low-resource settings may be of benefit. The objective of this study was to describe operative procedures performed for trauma at a tertiary care facility in Kigali, Rwanda, and to evaluate geographical variations and referral patterns of trauma care. METHODS: We retrospectively reviewed all prospectively collected operative cases performed at the largest referral hospital in Rwanda, the Centre Hospitalier Universitaire de Kigali (CHUK), between June 1 and Dec. 1, 2011, for injury-related diagnoses. We used the Pearson chi2 and Fisher exact tests to compare cases arising from within Kigali to those transferred from other provinces. Geospatial analyses were also performed to further elucidate transfer patterns. RESULTS: Over the 6-month study period, 2758 surgical interventions were performed at the CHUK. Of these, 653 (23.7%) were for trauma. Most patients resided outside of Kigali city, with 337 (58.0%) patients transferred from other provinces and 244 (42.0%) from within Kigali. Most trauma procedures were orthopedic (489 [84.2%]), although general surgery procedures represented a higher proportion of trauma surgeries in patients from other provinces than in patients from within Kigali (28 of 337 [8.3%] v. 10 of 244 [4.1%]). CONCLUSION: To our knowledge, this is the first study to highlight geographical variations in access to trauma care in a low income country and the first description of trauma procedures at a referral centre in Rwanda. Future efforts should focus on maturing prehospital and interfacility transport systems, strengthening district hospitals and further supporting referral institutions. PMID- 26812408 TI - Prevalence of musculoskeletal disorders among orthopedic trauma surgeons: an OTA survey. AB - BACKGROUND: Occupational injuries and hazards have gained increased attention in the surgical community in general and in the orthopedic literature specifically. The aim of this study was to assess prevalence and characteristics of musculoskeletal disorders among orthopedic trauma surgeons and the impact of these injuries on the surgeons' practices. METHODS: We sent a modified version of the physical discomfort survey to surgeon members of the Orthopaedic Trauma Association (OTA) via email. Data were collected and descriptive statistics were analyzed. RESULTS: A total of 86 surgeons completed the survey during the period of data collection; 84.9% were men, more than half were 45 years or older and 40.6% were in practice for 10 years or more. More than 66% of respondents reported a musculoskeletal disorder that was related to work; the most common was low back pain (29.3%). The number of body regions involved and disorders diagnosed was associated with increasing age and number of years in practice (p = 0.033). Time off work owing to these disorders was associated with working in a private setting (p = 0.045) and working in more than 1 institute (p = 0.009). CONCLUSION: To our knowledge, our study is the first to report a high percentage of orthopedic trauma surgeons sustaining occupational injuries some time in their careers. The high cost of management and rehabilitation of these injuries in addition to the related number of missed work days indicate the need for increased awareness and implementation of preventive measures. PMID- 26812409 TI - Mid-term survivorship and clinical outcomes of cobalt-chrome and oxidized zirconium on highly crosslinked polyethylene. AB - BACKGROUND: The choice of bearing articulation for total hip arthroplasty in younger patients is amenable to debate. We compared mid-term patient-reported outcomes and survivorship across 2 different bearing articulations in a young patient cohort. METHODS: We reviewed patients with cobalt-chrome or oxidized zirconium on highly crosslinked polyethylene who were followed prospectively between 2004 and 2012. Kaplan-Meier analysis was used to determine predicted cumulative survivorship at 5 years with all-cause and aseptic revisions as the outcome. We compared patient-reported outcomes, including the Harris hip score (HHS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and Short-form 12 (SF-12) scores. RESULTS: A total of 622 patients were followed during the study period. Mean follow-up was 8.2 (range 2.0-10.6) years for cobalt chrome and 7.8 (range 2.1-10.7) years for oxidized zirconium. Mean age was 54.9 +/- 10.6 years for cobalt-chrome and 54.8 +/- 10.7 years for oxidized zirconium. Implant survivorship was 96.0% (95% confidence interval [CI] 94.9%-97.1%) for cobalt-chrome and 98.7% (95% CI 98.0%-99.4%) for oxidized zirconium on highly crosslinked polyethylene for all-cause revisions, and 97.2% (95% CI 96.2%-98.2%) for cobalt-chrome and 99.0% (95% CI 98.4%-99.6%) for oxidized zirconium for aseptic revisions. An age-, sex- and diagnosis-matched comparison of the HHS, WOMAC and SF-12 scores demonstrated no significant changes in clinical outcomes across the groups. CONCLUSION: Both bearing surface couples demonstrated excellent mid-term survivorship and outcomes in young patient cohorts. Future analyses on wear and costs are warranted to elicit differences between the groups at long-term follow-up. PMID- 26812410 TI - Prevention of perineal hernia after laparoscopic and robotic abdominoperineal resection: review with illustrative case series of internal hernia through pelvic mesh. AB - ABSTRACT: This review is intended to raise awareness of placing a pelvic mesh to prevent perineal hernias in cases of minimally invasive (MIS) abdominoperineal resections (APR) and, in doing so, causing internal hernias through the mesh. In this article, we review the published literature and present an illustrative series of 4 consecutive cases of early internal hernia through a pelvic mesh defect. These meshes were placed to prevent perineal hernias after laparoscopic or robotic APRs. The discussion centres on 3 key questions: Should one be placing a pelvic mesh following an APR? What are some of the technical details pertaining to the initial mesh placement? What are the management options related to internal hernias through such a mesh? PMID- 26812411 TI - Evaluating if colonoscopies are essential after a diverticulitis diagnosis. PMID- 26812412 TI - Evaluating if colonoscopies are essential after a diverticulitis diagnosis - Author response. PMID- 26812413 TI - Operative or nonoperative management of Hinchey III purulent acute diverticulitis? PMID- 26812414 TI - Re: Recurrence of inguinal hernias repaired in a large surgical specialty hospital and general hospitals in Ontario, Canada. PMID- 26812416 TI - Towards deep inclusion for equity-oriented health research priority-setting: A working model. AB - Growing consensus that health research funders should align their investments with national research priorities presupposes that such national priorities exist and are just. Arguably, justice requires national health research priority setting to promote health equity. Such a position is consistent with recommendations made by the World Health Organization and at global ministerial summits that health research should serve to reduce health inequalities between and within countries. Thus far, no specific requirements for equity-oriented research priority-setting have been described to guide policymakers. As a step towards the explication and defence of such requirements, we propose that deep inclusion is a key procedural component of equity-oriented research priority setting. We offer a model of deep inclusion that was developed by applying concepts from work on deliberative democracy and development ethics. This model consists of three dimensions--breadth, qualitative equality, and high-quality non elite participation. Deep inclusion is captured not only by who is invited to join a decision-making process but also by how they are involved and by when non elite stakeholders are involved. To clarify and illustrate the proposed dimensions, we use the sustained example of health systems research. We conclude by reviewing practical challenges to achieving deep inclusion. Despite the existence of barriers to implementation, our model can help policymakers and other stakeholders design more inclusive national health research priority setting processes and assess these processes' depth of inclusion. PMID- 26812415 TI - The Incidence of End-Stage Renal Disease in the Diabetic (Compared to the Non Diabetic) Population: A Systematic Review. AB - End-stage renal disease (ESRD) in diabetes is a life threatening complication resulting in a poor prognosis for patients as well as high medical costs. The aims of this systematic review were (1) to evaluate the incidence of ESRD due to all causes and due to diabetic nephropathy in the diabetic population and differences between incidences of ESRD with respect to sex, ethnicity, age and regions, (2) to compare incidence rates in the diabetic and non-diabetic population, and (3) to investigate time trends. The systematic review was conducted according to the PRISMA group guidelines by performing systematic literature searches in the biomedical databases until January 3rd 2015; thirty two studies were included. Among patients with incident type 1 diabetes the 30 year cumulative incidence ranged from 3.3% to 7.8%. Among patients with prevalent diabetes, incidence rates of ESRD due to all causes ranged from 132.0 to 167.0 per 100,000 person-years, whereas incidence rates of ESRD due to diabetic nephropathy varied from 38.4 to 804.0 per 100,000 person-years. The incidence of ESRD in the diabetic population was higher compared to the non-diabetic population, and relative risks varied from 6.2 in the white population to 62.0 among Native Americans. The results regarding time trends were inconsistent. The review conducted demonstrates the considerable variation of incidences of ESRD among the diabetic population. Consistent findings included an excess risk when comparing the diabetic to the non-diabetic population and ethnic differences. We recommend that newly designed studies should use standardized methods for the determination of ESRD and population at risk. PMID- 26812417 TI - Dimensions of Cognitive Closure. AB - This study investigated the generality of the perceptual factors of speed and flexibility of closure in the cognitive domain. Several experimental measures of both flexibility and speed of closure employing perceptual or figural content, verbal or symbolic content, and semantic content were administered to 541 Naval Aviation Cadets, along with marker measures for several established factors. In addition to several of these marker dimensions, factors were obtained for both flexibility and speed of figural closure, of verbal or symbolic closure, and of semantic closure, along with a dimension tentatively interpreted as flexibility of grammatical closure. The substantial intercorrelations among these factors yielded four second-order dimensions, interpreted as analytical functioning or general reasoning, figural closure, symbolic closure, and semantic closure. The latter three factors each represent a combination of analytical and structuring skills (a coalescence of flexibility and speed of closure) and are distinguished by the type of content involved (figure, symbol, or meaning). PMID- 26812418 TI - A Score Matrix for Thurstone's Box Problem. AB - Since the score matrix for Thurstone's classic 20-variable box problem contains no measurement error and also genera1,es a singular correlation matrix, a new score matrix for this problem, both containing measurement error and having enough entities to yield a nonsingular correlation matrix, is developed. Various interesting statistics for the new data are given, and an extended vector projection for the new data is shown. The new score matrix should be of use for work in factor-analytic methodology. PMID- 26812419 TI - Anxiety Profiles Based on Both Situational and Response Factors. AB - It was argued that a comprehensive picture of an individual's anxiety pattern could be obtained by taking into account different types of anxiety reactions and different categories of stressful situations reacted to. An anxiety inventory utilizing these two factors was analyzed with regard to the anxiety profiles of different subgroups of 116 adolescents. The original situation and response scales were categorized on the basis of factor analyses, in order to reduce the total matrix. Ss with similar response profiles across categories of situations were classified in homogeneous groups using latent profile analysis (LPA). For each sex, three categories of individuals were obtained, two of which differed mainly in anxiety level whereas the their group was characterized by a high transsituational inconsistency. For the total sample of Ss, "Psychic" responses were reported as more intense than "Somatic" responses and "Anticipation fear" situations were reported as less anxiety provoking than "Inanimate threat" situations and "Threat of punishment" situations. PMID- 26812420 TI - A Conjugate Gradient Algorithm for the Multidimensional Analysis of Preference Data. AB - In continuation of earlier work on a new individual difference model for the multidimensional analysis of preference data (Schonemann and Wang, 1972), a relatively efficient algorithm for applying the model to fallible data was developed. It is based on the Method of Conjugate Gradients and thus does not require storage for second order derivatives. Several different versions of such an algorithm were compared ill terms of robustness, accuracy, and speed of convergence. The results strongly suggest that the so-called "intervening conjugate gradient method" (which iterates for only two of the three sets of unknowns and solves for the third set algebraically at each stage) is the most effective method for most purposes. The algorithm was applied to a relatively large set of political choice data which had bee previously analyzed by a different method. The outcome of this empirical study not only confirmed the earlier results but also led, as a consequence of the stronger metric structure of the present model, to a more detailed an informative description of the data. PMID- 26812421 TI - A Multivariate Analysis of Selected Class Characteristic and Student Rating of Instruction. AB - This study examined the relationship between selected class characteristics and student ratings of instructors. A large number of classes (N = 1247)and students (over 33,000) a t a large Midwestern University provided the data for this study. The results indicated that the class characteristics that had the strongest influence on the results of instructor ratings were the grades expected by students and the percentage of students in the class taking the course as an elective. PMID- 26812422 TI - An Approximate Confidence Interval for Maximum Coefficient Alpha. AB - An approximate confidence interval is developed for the maximum coefficient alpha reliability of a scale where the scale is considered fixed an persons are sampled. PMID- 26812423 TI - The Relation Between Rao's Paradox in Discriminate Analysis and Regression Analysis. AB - Rao has commented on an apparent paradox in discriminant analysis in which two variables discriminate the groups when used separately, but not in combination. It is shown that there is an exact relationship between this an the paradoxes in regression analysis. An expression for the F statistic in discriminant analysis is given in terms of the average of squares of t value to clarify this relationship. PMID- 26812424 TI - Repeatability of Principal Components in Samples: Normal and Non-Normal Data Sets Compared. AB - The asymptotic theory of the distribution of the latent roots and vector of principal components analysis (PCA) of samples has hitherto been tied t multivariate normal (MVN) distributions. However, much real behavior dat are not normal. The results of the present study show, using arguments base on Monte Carlo methods, that if there is enough meaningful structure in th population, then PCA of samples of data with multivariate non-normal (NN distribution may provide answers relative to the "true" population principal components (PC) of comparable reliability to PCA of samples of MVAT data. PMID- 26812425 TI - Brief Report: Asymmetric Simplicity Criteria for Orthogonal Factor Transformation. AB - The notion of column simplicity in a factor pattern matrix is discussed, and the varimax procedure is shown to be only one way of operatioializing this notion. A general central-moment simplicity criterion is introduced, an the special cases of this formulation that indicate asymmetry are shown t have logical appeal in a constraint-free factor transformation context. The results of implementing these criteria with data, however, suggest that., in the case of orthogonal rotation, the considerable constraints render solutions based on various special cases of the general criterion quite similar to one another. PMID- 26812426 TI - Effect of Fc-Glycan Structure on the Conformational Stability of IgG Revealed by Hydrogen/Deuterium Exchange and Limited Proteolysis. AB - Human therapeutic immunoglobulin gamma (IgG) molecules contain an N-glycan on each of their Fc CH2 domains. These glycans include high-mannose, hybrid, and complex types. Recombinant IgG molecules containing high-mannose glycans have been shown to clear faster in human blood, and exhibit decreased thermal stability. The molecular mechanism behind these observations, however, is not well understood. In this work, we used hydrogen/deuterium exchange combined with mass spectrometry (HDX MS), as well as proteolytic degradation under a native like condition, to assess the impact of different glycoforms on the molecular structure and stability of recombinant IgG1 and IgG2 molecules expressed from Chinese hamster ovary cells. Our HDX MS data indicate that the conformation of these IgG molecules was indeed influenced by the glycan structure. IgG molecules containing high-mannose and hybrid glycans showed more conformational flexibility in the CH2 domain. This conclusion was further supported by the analysis of glycopeptides released from these molecules by trypsin digestion under a native like condition. The higher CH2 conformational flexibility of IgG molecules with high-mannose and hybrid glycans contributes to their decreased thermal stability. IgG molecules containing sialylated glycans in the CH2 domain exhibited similar enzymatic degradation behavior as high-mannose glycans, suggesting decreased CH2 domain stability compared to shorter complex glycans, likely resulting from steric effect that decreased the glycan-CH2 domain interaction. PMID- 26812427 TI - Hepatobiliary and Pancreatic: Leiomyosarcoma: unusual cause of inferior vena cava obstruction. PMID- 26812428 TI - From the Editor-in-Chief's Desk. PMID- 26812429 TI - Breast Cancer in Young Women: Research Priorities. A Report of the Young Survival Coalition Research Think Tank Meeting. AB - Breast cancer in young women is a significant issue-7% of all female breast cancer is diagnosed in women under 40 years of age. Young women with breast cancer (YWBC) face significant and unique challenges, including a higher likelihood of biologically aggressive disease and metastatic disease at diagnosis, leading to poorer prognosis, more aggressive treatment and long-term treatment-related toxicities, and unique psychosocial concerns. This article summarizes the Young Survival Coalition (YSC) Research Think Tank Meeting, held in Arlington, Virginia, in February 2013, and presents the process that led to YSC's priorities for YWBC research. The meeting's participants focused on six broad categories of investigation in which additional advancements in research on YWBC are crucial: risk factors; treatment; fertility; pregnancy-associated breast cancer; quality of life and survivorship; and metastasis. Several key themes emerged from this meeting. Researchers and advocates felt that a large-scale data registry focused on YWBC is necessary to collect quality information to guide future research for YWBC. This database should include clinical data, genomic profiling of primary tumor and metastatic sites, and an increased focus on fertility and pregnancy following breast cancer treatment. The participants also felt that more must be done to elucidate how and why YWBC develop more aggressive tumors, and to what degree treatment should be modified for young women. The discussions summarized here led to the formulation of YSC's Research Agenda, published in May 2014. PMID- 26812430 TI - An Innovative Website in the United States for Meeting the Emotional and Supportive Care Needs of Young Adults with Cancer. AB - This paper describes the development of an institution-specific website designed to meet the supportive and emotional needs of young adults (18-39 years old) with cancer in the United States. The website contains information about topics of particular interest to young adults, coping skills education, and resources; and has social networking capacity. In a survey of website users, participants reported increased "connectedness" and variable impact on feelings of sadness, fear, and worry. Recommendations are made for fostering peer interactions, encouraging staff to educate website users around self-monitoring for distress, and incorporating relevant content on the website. PMID- 26812431 TI - Extramedullary Breast Relapse of Acute Lymphoblastic Leukemia Controlled with a Second Allogeneic/Autologous Hematopoietic Cell Transplant. AB - Relapse of acute lymphoblastic leukemia (ALL) in the breast is uncommon and often precedes systemic relapse, resulting in poor survival. We report the development of breast involvement of ALL in a 20-year-old woman 32 months after a related allogeneic peripheral blood hematopoietic cell transplantation (PBHCT) in first remission. This extramedullary relapse occurred in the continuous presence of complete donor chimerism. After systemic re-induction chemotherapy and a second PBHCT using donor cells that had been cryopreserved at first transplant, our patient has remained in second complete remission for more than 44 months. PMID- 26812433 TI - Atomic/Molecular Layer Deposition of Lithium Terephthalate Thin Films as High Rate Capability Li-Ion Battery Anodes. AB - We demonstrate the fabrication of high-quality electrochemically active organic lithium electrode thin films by the currently strongly emerging combined atomic/molecular layer deposition (ALD/MLD) technique using lithium terephthalate, a recently found anode material for lithium-ion battery (LIB), as a proof-of-the-concept material. Our deposition process for Li-terephthalate is shown to well comply with the basic principles of ALD-type growth including the sequential self-saturated surface reactions, a necessity when aiming at micro-LIB devices with three-dimensional architectures. The as-deposited films are found crystalline across the deposition temperature range of 200-280 degrees C, which is a trait highly desired for an electrode material but rather unusual for hybrid inorganic-organic thin films. Excellent rate capability is ascertained for the Li terephthalate films with no conductive additives required. The electrode performance can be further enhanced by depositing a thin protective LiPON solid state electrolyte layer on top of Li-terephthalate; this yields highly stable structures with capacity retention of over 97% after 200 charge/discharge cycles at 3.2 C. PMID- 26812434 TI - Real-Time PCR for Measles Virus Detection on Clinical Specimens with Negative IgM Result in Morocco. AB - Since the confirmation of measles cases represents an important indicator regarding the performance of the measles-elimination program, the aim of this study was to evaluate the effectiveness of the routine procedures followed in Morocco for the laboratory confirmation of measles cases. Suspected cases reported between January 2010 and December 2012 were assessed for the timeliness of the sample collection, occurrence of measles clinical symptoms, and the results of the laboratory diagnoses. For 88% of the 2,708 suspected cases, a clinical specimen was collected within 7d of rash onset, of which 50% were IgM positive and 2.6% were equivocal. The measles symptoms were reported in 91.4% of the cases; the occurrence of symptoms showed a positive association with the serological results (odds ratio [OR] = 2.9883, 95% confidence interval [CI] 2.2238-4.0157). Of the negative samples, 52% (n = 116) tested positive by real time polymerase chain reaction (PCR). These results are in favor of using molecular detection to complement serological diagnosis in the context of measles surveillance approach in Morocco. In addition, the introduction of additional laboratory methods for differential diagnosis is required for the final classification of suspected cases with maculopapular rash and fever in the context of the measles elimination program. PMID- 26812435 TI - Cog-Wheel Octameric Structure of RS1, the Discoidin Domain Containing Retinal Protein Associated with X-Linked Retinoschisis. AB - RS1, also known as retinoschisin, is a disulphide-linked, discoidin domain containing homo-oligomeric protein that plays a crucial role in maintaining the cellular and synaptic organization of the retina. This is highlighted by the finding that over 130 mutations in RS1 cause X-linked retinoschisis, a retinal degenerative disease characterized by the splitting of the retinal cell layers, disruption of the photoreceptor-bipolar synapses, degeneration of photoreceptors, and severe loss in central vision. In this study, we investigated the arrangement of the RS1 subunits within the oligomer complex using single particle electron microscopy. RS1 was seen as two stacked rings with each ring displaying a symmetrical cog wheel-like structure with eight teeth or projections corresponding to the RS1 subunits. Three dimensional reconstruction and molecular modelling indicated that the discoidin domain, the principal functional unit of RS1, projects outward, and the Rs1 domain and C-terminal segment containing intermolecular disulphide bonds are present in the inner ring to form the core octameric structure. These studies provide a basis for further understanding the role of the novel core RS1 octameric complex in retinal cell biology and X-linked retinoschisis. PMID- 26812436 TI - A novel HLA-B allele, HLA-B*35:254, identified by sequence-based typing from a HIV-associated tuberculosis sufferer. AB - HLA-B*35:254 differs from HLA-B35:25 by two coding changes at nucleotides positions 142 (T > G) and 292 (T > G). PMID- 26812437 TI - Assessing Patients' Disaster Preparedness in Home-Based Primary Care. AB - BACKGROUND: Chronic conditions paired with normal aging put home-bound individuals at risk of harm during a disaster. Because of their high rate of comorbidities, veterans receiving care from the Veterans Health Administration (VHA)'s home-based primary care (HBPC) program are especially vulnerable, which may prevent them from being prepared for disaster. With intimate knowledge of their patients' home environments, medical needs, resources, and limitations, HBPC practitioners are uniquely positioned to assess and improve disaster preparedness of patients. OBJECTIVE: This study explored issues regarding disaster preparedness for HBPC patients, including ways in which policy and procedures support routine assessment of disaster preparedness for patients as well as patient education activities. METHODS: This project involved 32 semi structured interviews with practitioners and leadership at 5 VHA HBPC programs - 3 urban and 2 rural. Transcripts of the interviews were analyzed using content analysis techniques. RESULTS: Three themes emerged regarding the assessment of a patient's disaster preparedness: (1) assessment tools are rudimentary and, in some cases, individually developed by practitioners; (2) comprehension of criteria for assigning risk categories varies among practitioners, and (3) patients' cognitive impairment, limited resources, and out-of-date or inaccessible materials are the primary challenges to their preparedness. A fourth additional theme emerged as well: (4) the interdisciplinary nature of the HBPC team allows for unique innovative practices, such as a central focus on caregiver support and personal safety, as it relates to assessment and preparedness of the patient. CONCLUSION: Health and functional limitations may prevent home-bound patients from being adequately prepared for disasters. Standardized strategies and tools concerning disaster preparedness assessment for HBPC patients, which allow flexibility in consideration of factors such as local hazards, could assist in creating more comprehensive planning approaches and, in turn, more prepared persons. PMID- 26812438 TI - An Independent Evaluation of the CryoXtract Instruments' CXT350 Frozen Sample Aliquotter Using Tissue and Fecal Biospecimens. AB - The ability to take targeted multiple cores from a single frozen biospecimen would enable several research projects to be fueled from one biospecimen, a small piece of tissue to be quality-control tested, and for pathologically-discrete areas of a biospecimen (e.g., tumor, stromal, and normal tissue) to be selectively sampled for comparative analyses. CryoXtract Instruments' CXT350 Frozen Sample Aliquotter can potentially achieve this by producing multiple cores from one cryopreserved biospecimen without thawing either the parent biospecimen or its daughter cores. It therefore has the potential to add significant value to a tissue banking workflow. We have evaluated its performance while using 614 cores from fecal, liver, kidney, lung, heart, and colon biospecimens. Coring densities of up to five complete and four fragmentary cores per cm(3) are achievable using 3 mm coring probes. Median core weights for tissue were 14.1 17.2 mg (depending on tissue type) and cores <=325 mg could be taken from fecal biospecimens (depending on the fill-depth of the tube). The coefficient of variation for multiple cores taken from a fecal biospecimen was 11.7%. Between sample contamination did not occur. RNA Integrity numbers and qRT-PCR analysis demonstrated that coring induced a statistically significant impact on RNA quality that was inconsequential in magnitude and in our view does not represent a barrier for the effective utilization of the technology. PMID- 26812439 TI - High-pass filters and baseline correction in M/EEG analysis-continued discussion. PMID- 26812440 TI - Microwave-Assisted Synthesis of Reduced Graphene Oxide/SnO2 Nanocomposite for Oxygen Reduction Reaction in Microbial Fuel Cells. AB - We report on an easy, fast, eco-friendly, and reliable method for the synthesis of reduced graphene oxide/SnO2 nanocomposite as cathode material for application in microbial fuel cells (MFCs). The material was prepared starting from graphene oxide that has been reduced to graphene during the hydrothermal synthesis of the nanocomposite, carried out in a microwave system. Structural and morphological characterizations evidenced the formation of nanocomposite sheets, with SnO2 crystals of few nanometers integrated in the graphene matrix. Physico-chemical analysis revealed the formation of SnO2 nanoparticles, as well as the functionalization of the graphene by the presence of nitrogen atoms. Electrochemical characterizations put in evidence the ability of such composite to exploit a cocatalysis mechanism for the oxygen reduction reaction, provided by the presence of both SnO2 and nitrogen. In addition, the novel composite catalyst was successfully employed as cathode in seawater-based MFCs, giving electrical performances comparable to those of reference devices employing Pt as catalyst. PMID- 26812441 TI - Dynamics of Aqueous Droplets at the Interface of Coflowing Immiscible Oils in a Microchannel. AB - We report the dynamics of aqueous droplets of different size and viscosity at the interface of a coflowing stream of immiscible oils (i.e., primary and secondary continuous phases) in a microchannel, at low Re. The lateral migration of droplets introduced into the primary continuous phase toward the interface and subsequent selective migration of droplets across the interface into the secondary continuous phase is investigated. The interplay between the competing noninertial lift and interfacial tension forces, which govern the interfacial migration of the droplets, is presented and discussed. The velocity and strain rate profiles, and interface location, which are critical for calculating the lift force and migration behavior of droplets, are presented. The trajectories of droplets of different size and viscosity in the primary continuous phase are obtained for different interface locations. During interfacial migration, the deformation behavior of droplets of different viscosities is studied. Finally, sorting of droplets based on size contrast is demonstrated and sorting efficiency is found. A new paradigm of migration and sorting of droplets is reported, which could find importance in chemical and biological applications. PMID- 26812442 TI - EEG Brain Wave Activity at Rest and during Evoked Attention in Children with Attention-Deficit/Hyperactivity Disorder and Effects of Methylphenidate. AB - OBJECTIVE: The aim of this study was to assess baseline EEG brain wave activity in children with attention-deficit/hyperactivity disorder (ADHD) and to examine the effects of evoked attention and methylphenidate on this activity. METHOD: Children with ADHD (n = 19) were tested while they were stimulant free and during a period in which they were on stimulant (methylphenidate) medication. Control subjects (n = 18) were tested once. EEG brain wave activity was tested both at baseline and during focussed attention. Attention was evoked and EEG brain wave activity was determined by means of the BioGraph Infiniti biofeedback apparatus. RESULTS: The main finding of this study was that control subjects and stimulant free children with ADHD exhibited the expected reactivity in high alpha-wave activity (11-12 Hz) from baseline to focussed attention; however, methylphenidate appeared to abolish this reactivity. CONCLUSION: Methylphenidate attenuates the normal cortical response to a cognitive challenge. PMID- 26812443 TI - Toward Structural Correctness: Aquatolide and the Importance of 1D Proton NMR FID Archiving. AB - The revision of the structure of the sesquiterpene aquatolide from a bicyclo[2.2.0]hexane to a bicyclo[2.1.1]hexane structure using compelling NMR data, X-ray crystallography, and the recent confirmation via full synthesis exemplify that the achievement of "structural correctness" depends on the completeness of the experimental evidence. Archived FIDs and newly acquired aquatolide spectra demonstrate that archiving and rigorous interpretation of 1D (1)H NMR data may enhance the reproducibility of (bio)chemical research and curb the growing trend of structural misassignments. Despite being the most accessible NMR experiment, 1D (1)H spectra encode a wealth of information about bonds and molecular geometry that may be fully mined by (1)H iterative full spin analysis (HiFSA). Fully characterized 1D (1)H spectra are unideterminant for a given structure. The corresponding FIDs may be readily submitted with publications and collected in databases. Proton NMR spectra are indispensable for structural characterization even in conjunction with 2D data. Quantum interaction and linkage tables (QuILTs) are introduced for a more intuitive visualization of 1D J coupling relationships, NOESY correlations, and heteronuclear experiments. Overall, this study represents a significant contribution to best practices in NMR-based structural analysis and dereplication. PMID- 26812444 TI - Hemorrhagic Fever with Renal Syndrome, Zibo City, China, 2006-2014. AB - Analysis of hemorrhagic fever with renal syndrome cases in Zibo City, China, during 2006-2014 showed that it occurred year-round. Peaks in spring and fall/winter were caused by Hantaan and Seoul viruses, respectively. Rodent hosts were the striped field mouse for Hantaan virus and the brown rat and house mouse for Seoul virus. PMID- 26812445 TI - Emerging infections caused by non-Aspergillus filamentous fungi. AB - There are three broad groups of non-Aspergillus moulds: the mucormycetes, the hyalohyphomycetes and the phaeohyphomycetes. Infections with these pathogens are increasingly reported, particularly in the context of increasing use of immunosuppressant agents and improved diagnostics. The epidemiology of non Aspergillus mould infections varies with geography, climate and level of immunosuppression. Skin and soft-tissue infections are the predominant presentation in the immunocompetent host and pulmonary and other invasive infections in the immunocompromised host. The more common non-Aspergillus moulds include Rhizopus, Mucor, Fusarium and Scedosporium species; however, other emerging pathogens are Rasamsonia and Verruconis species, which are discussed in this article. Outbreaks of non-Aspergillus mould infections have been increasingly reported, with contaminated medical supplies and natural disasters as common sources. Currently culture and other conventional diagnostic methods are the cornerstone of diagnosis. Molecular methods to directly detect and identify mould pathogens in tissue and body fluids are increasingly used. PMID- 26812446 TI - Rapid decline of fasting glucose in HCV diabetic patients treated with direct acting antiviral agents. AB - Association between hepatitis C virus (HCV) infection and diabetes has been widely postulated. Little is known about the effect of direct-acting antiviral agents (DAAs) on glycaemic control. The aim of our study was to evaluate the glycaemic control modifications in a case series of HCV-positive diabetic patients receiving DAAs. We retrospectively evaluated 149 HCV-positive patients in two different institutions affiliated with Sapienza University: Policlinico Umberto I of Rome and Ospedale Santa Maria Goretti of Latina. We were able to identify 29 patients with type 2 diabetes mellitus (19% of total population) who were receiving different interferon-free regimens. During-treatment fasting glucose (FG) values were available for 21 patients, and analysis revealed a statistically significant reduction (p 0.007); reduction mean value was -52.86 mg/dL. A glycated haemoglobin (A1C) value during treatment (at weeks 4, 8 and/or 12) was available for ten patients, and the analysis revealed a statistically significant reduction (p 0.021) with a reduction mean value of -1.95%. Six patients (23%) needed to reduce hypoglycaemic drugs, eight of ten patients showed reduction of A1C and 14 (67%) of 21 patients showed reduced FG during treatment. FG and A1C reductions values were independent from which DAA was present in the regimen, HCV genotype, body mass index and HIV status. In order to avoid hypoglycaemic events, diabetic patients receiving DAAs should be closely monitored for reduction of hypoglycaemic drugs. Furthermore, in our opinion, diabetes could be considered as an element to prioritize treatment in those patients with no apparent liver disease. PMID- 26812447 TI - Probing the Crystal Structure, Composition-Dependent Absolute Energy Levels, and Electrocatalytic Properties of Silver Indium Sulfide Nanostructures. AB - The absolute electronic energy levels in silver indium sulfide (AIS) nanocrystals (NCs) with varying compositions and crystallographic phases have been determined by using cyclic voltammetry. Different crystallographic phases, that is, metastable cubic, orthorhombic, monoclinic, and a mixture of cubic and orthorhombic AIS NCs, were studied. The band gap values estimated from the cyclic voltammetry measurements match well with the band gap values calculated from the diffuse reflectance spectra measurements. The AIS nanostructures were found to show good electrocatalytic activity towards the hydrogen evolution reaction (HER). Our results clearly establish that the electronic and electrocatalytic properties of AIS NCs are strongly sensitive to the composition and crystal structure of AIS NCs. Monoclinic AIS was found to be the most active HER electrocatalyst, with electrocatalytic activity that is almost comparable to the MoS2 -based nanostructures reported in the literature, whereas cubic AIS was observed to be the least active of the studied crystallographic phases and compositions. In view of the HER activity and electronic band structure parameters observed herein, we hypothesize that the Fermi energy level of AIS NCs is an important factor that decides the electrocatalytic efficiency of these nanocomposites. The work presented herein, in addition to being the first of its kind regarding the composition and phase-dependence of electrochemical aspects of AIS NCs, also presents a simple solvothermal method for the synthesis of different crystallographic phases with various Ag/In molar ratios. PMID- 26812448 TI - Sonologic enthesitis in children with enthesitis-related arthritis. AB - OBJECTIVES: Enthesitis is an important clinical manifestation and is a diagnostic criterion for juvenile idiopathic enthesitis-related arthritis (JIA-ERA). Ultrasound (US) is a highly sensitive method of detection of enthesitis in adult spondyloarthropathies. However, since the data on JIA and the preformance of US compared to clinical examination is limited, we aimed to compare the accuracy of US and clinical examination in JIA-ERA. METHODS: Patients with JIA-ERA (ILAR criteria) were enrolled in the study after consent. Besides data on disease variables, enthesitis was evaluated clinically as well as by ultrasound. Six entheseal sites (iliac crest, superior pole patella, inferior pole patella, tibial tuberosity, tendoachilles and plantar fascia) on both sides of the body were examined in each patient. Features of acute and chronic enthesitis were noted. RESULTS: 360 entheseal sites in 30 male patients (26 positive for HLA B27), with a median age of 16 years and median disease duration of 4 years were evaluated. Median Madrid Sonology Enthesitis Index (MSEI) was 2.0 (MSEI-Acute) (IQR 0-3) and 1.0 (MSEI-Chronic) (IQR 0-1). Ultrasound enthesitis was seen in 25 of 30 patients whereas clinical enthesitis was present in 15 patients only. USG picked up 20 (47 vs. 27) more sites of enthesitis as compared to clinical examination. The concordance rate was 89.4%. Discordance was more at tibial tuberosity, superior pole patella and tendoachilles entheses. CONCLUSIONS: Ultrasonography detects subclinical enthesitis in a proportion of patients with JIA-ERA. It can be a useful, cost-effective and safe diagnostic tool in the workup of JIA patients. PMID- 26812449 TI - Management of Adolescent Low-Risk Classical Hodgkin Lymphoma: Which Chemotherapy Backbone Gives the Best Chance of Omitting Radiotherapy Safely. AB - Even though more than 90% of adolescents with low-risk classical Hodgkin lymphoma (LRcHL) will be cured with first-line therapy, many will suffer serious late toxic effects from radiotherapy (RT). The goals for care have shifted toward minimizing late toxic effects without compromising the outstanding cure rates by adapting a risk and response-based therapy. Recent published and ongoing randomized clinical trials, using functional imaging, may allow for better identification of those patients for whom RT may be safely omitted while maintaining excellent cure rates. To evaluate the best chemotherapy regimens with a reasonable toxicity profile and that are expected to have a high chance of omitting RT based on a response-directed therapy while maintaining high cure rates, a mini review was conducted of the recent clinical trials in pediatric and adult LRcHL. The UK RAPID trial chemotherapy backbone (3 * ABVD) followed by a response-based positron emission tomography scan offers up to a 75% chance of safely omitting RT without compromising the cure rate, which remained well above 90%. PMID- 26812450 TI - Randomized Trial of a Physical Activity and Meditation Intervention for Young Adult Cancer Survivors. AB - PURPOSE: Young adult cancer survivors have a number of increased health and psychosocial risks. To minimize these risks, they must address any modifiable risk factors, for example increase their physical activity (PA) and reduce stress. Unfortunately, more than half of young survivors remain sedentary, and few participate in a structured form of relaxation. This study evaluated the feasibility, acceptability, and effects of a theory-based PA and meditation intervention for young survivors. METHODS: Young adult cancer survivors (age 18 39 years) were randomized to receive the 12-week "RElaxation aNd Exercise for Wellness" (RENEW) intervention right away (intervention group) or after a 12-week wait (control group). Participants were assessed at baseline, 12 weeks, and 24 weeks. RESULTS: Thirty-five survivors were enrolled and randomized. Results indicate that 89% of intervention calls were delivered, and most participants felt that intervention goals and the number and duration of intervention calls were appropriate. Satisfaction ratings indicate that the intervention was acceptable, and 100% of participants would recommend it to others. Comparison of the intervention and control groups at the 12-week assessment (i.e., before controls received the intervention) revealed that the intervention group was performing more minutes of at least moderate intensity PA/week (p = 0.002; M = 113.8, SE = 23.5 vs. M = -8.7, SE = 27.1) and outperformed controls on a test of cardiovascular fitness (p = 0.008; M = -1.76, SE = 0.41 vs. M = -0.03, SE = 0.45). When data from the intervention and control groups were pooled, pre- to post-intervention analyses indicated a trend toward improved mood. CONCLUSION: This theory-based intervention for young adult cancer survivors was feasible and acceptable, and may have helped survivors increase PA, improve fitness, and enhance mood. PMID- 26812451 TI - Disparities in Adolescent and Young Adult Survival After Testicular Cancer Vary by Histologic Subtype: A Population-Based Study in California 1988-2010. AB - PURPOSE: Testicular cancer is the most common cancer among adolescent and young adult (AYA) men 15-39 years of age. This study aims to determine whether race/ethnicity and/or neighborhood socioeconomic status (SES) contribute independently to survival of AYAs with testicular cancer. METHODS: Data on 14,249 eligible AYAs with testicular cancer diagnosed in California between 1988 and 2010 were obtained from the population-based California Cancer Registry. Multivariable Cox proportional hazards regression was used to examine overall and testicular cancer-specific survival and survival for the seminoma and nonseminoma histologic subtypes according to race/ethnicity, census-tract level neighborhood SES, and other patient and clinical characteristics. RESULTS: Compared with White AYAs, Hispanic AYAs had worse overall and testicular cancer-specific survival (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.07-1.37) and Black AYAs had worse overall survival (HR, 1.41; 95% CI, 1.01-1.97), independent of neighborhood SES and other demographic and clinical factors. Racial/ethnic disparities in survival were more pronounced for nonseminoma than for seminoma. AYAs residing in middle and low SES neighborhoods experienced worse survival across both histologic subtypes independent of race/ethnicity and other factors, while improvements in survival over time were more pronounced for seminoma. Longer time to treatment was also associated with worse survival, particularly for AYAs with nonseminoma. CONCLUSION: Among AYAs, race/ethnicity, and neighborhood SES are independently associated with survival after testicular cancer. Variation in disparities by histologic type according to demographic factors, year of diagnosis, and time to treatment may reflect differences in prognosis and extent of treatment for the two histologies. PMID- 26812453 TI - A Review of Cardiorespiratory Fitness in Adolescent and Young Adult Survivors of Childhood Cancer: Factors that Affect its Decline and Opportunities for Intervention. AB - Childhood cancer incidence and survivorship rates are increasing, leading to a growing population of survivors that are at risk for competing causes of death, most notably cardiovascular disease (CVD). Cardiorespiratory fitness (CRF), a key modifiable CVD risk factor, is lower than expected among childhood survivors 5-20 years post-diagnosis. This review discusses the studies that demonstrate lower CRF in survivors of childhood cancer and the potential mechanisms and factors contributing to lower CRF in this population. Both exercise interventions and strategies to improve CRF are considered. The review advocates for more robust clinical research and exercise interventions to improve CRF with the goal of reducing comorbidities and competing CVD risk among childhood cancer survivors into adolescence and young adulthood. PMID- 26812452 TI - Fertility Issues in Adolescent and Young Adult Cancer Survivors. AB - PURPOSE: Many adolescent and young adult (AYA) cancer survivors place great importance on fertility. This study explored AYAs' discussions of fertility in the context of discussing their survivorship experiences. METHODS: Secondary analyses of a qualitative study of young adult survivors of adolescent cancers ("AYA survivors") was performed using semistructured individual interviews and focus groups. Analyses were conducted using grounded theory using thematic content analysis with an inductive data-driven approach. RESULTS: Participants (n = 43) were 16-24 years old, diagnosed with cancer between ages 14 and 18 years, and were at least 6 months post-treatment. Before treatment, 5 males banked sperm and no females preserved fertility. More males (50%) than females (39%) reported uncertainty about their fertility. Three major categories emerged from the data: fertility concerns, emotions raised when discussing fertility, and strategies used to manage fertility concerns. Fertility concerns focused on dating/partner reactions, health risks, and what potential infertility would mean for their life narrative. Emotions included distress, feeling overwhelmed and hopeful/wishful thinking. Females were more likely to feel distressed and overwhelmed than males. Strategies to manage concerns included acceptance/"making do," desire to postpone concerns, and reliance on assisted reproductive technology. CONCLUSIONS: Most AYAs in our study reported a number of reproductive concerns and fertility related distress after treatment, which may affect other areas of psychosocial functioning. Females may be more at-risk for distress than males, particularly in situations of uncertainty and limited knowledge. Future work should explore how to best incorporate fertility-related informational and support services more fully into survivorship care. Implications for survivorship care are discussed. PMID- 26812454 TI - Fertility Preservation Counseling for Pediatric and Adolescent Cancer Patients. AB - PURPOSE: Fertility preservation for children and young adults with cancer is an important part of comprehensive patient care. In 2013, the American Society of Clinical Oncology (ASCO) released updated clinical practice guidelines addressing fertility preservation. This study aimed to evaluate if pediatric oncologists were performing fertility preservation counseling, if the new guidelines were being adopted, and how reproductive endocrinologists can educate this patient population and their providers. METHODS: A cross-sectional study was performed from May 26, 2014, to August 26, 2014. An online survey addressing fertility preservation practice patterns was created and provided to the members of the Children's Oncology Group (COG). RESULTS: Thirty-five percent of the 234 respondents reported reading the new 2013 ASCO guidelines. Ninety-five percent of providers reported mentioning fertility preservation options prior to treatment, most commonly including referral to a reproductive endocrinologist (28%), and sperm banking (57%). The most commonly reported barrier to fertility preservation counseling was the cost of treatment. CONCLUSION: Fertility preservation counseling is being performed by pediatric oncology providers. Familiarity of the ASCO guidelines is limited, revealing that the established methods for fertility preservation in women--embryo and oocyte cryopreservation--may be offered less than experimental methods in this younger patient population. Such differences in apparent practice patterns highlight the need for more education for providers. PMID- 26812455 TI - Validation of a Health Literacy Measure for Adolescents and Young Adults Diagnosed with Cancer. AB - Health literacy can influence long-term health outcomes. This study aimed to validate an adapted version of the Functional, Communicative and Critical Health Literacy measure for adolescent and young adult (AYA) cancer patients and survivors (N = 105; age 12-24 years). Exploratory factor analysis was used to validate the measure, and indicated that a slightly modified item structure better fit the results. Furthermore, item response theory analysis highlighted location and discrimination parameter differences among items. Acceptability of the measure was high. This is the first validation of a health literacy measure among AYAs with an illness such as cancer. PMID- 26812456 TI - A Grounded Theory Investigation into the Psychosexual Unmet Needs of Adolescent and Young Adult Cancer Survivors. AB - PURPOSE: For many adolescents and young adults (AYAs) with cancer, psychosexual well-being is compromised due to the onset of illness at a vulnerable stage of sexual development. To date, prior studies have focused on the psychosexual well being of older adult survivors, largely ignoring AYAs. Furthermore, the few studies investigating AYA psychosexual well-being have been prematurely quantitative in nature, limited by a lack of in-depth exploration regarding the unique psychosexual experiences of AYA survivors. Qualitative research is required to better identify and understand the unique complexities surrounding psychosexual needs among AYAs with cancer. METHODS: Semi-structured interviews were conducted with 11 AYA cancer survivors (aged 15-45 years at the time of diagnosis). Transcripts were coded using a grounded theory methodology. RESULTS: Constant comparison data analysis gave rise to the Pathways to Problems model, denoting the pathways to psychosexual unmet needs among AYA survivors. Participants experienced identity conflict, whereby an incongruity occurred between their chronological age and their self-perceived age. The experience of identity conflict, combined with changes to intimate relationships, shifts in priorities, physicians' assumptions, and inadequate support, contributed to the onset of psychosexual unmet needs. Six areas of psychosexual unmet needs were identified: fertility concerns, sexual communication, dealing with side effects, dating and disclosure, relating to other AYAs, and reconciling identity conflict. CONCLUSION: The present findings provide evidence for shared and unique psychosexual unmet needs among AYA survivors. Practical implications include the need for validation and incorporation of unique AYA unmet needs into screening tools and care plans, as well as peer support. PMID- 26812457 TI - Experiences of Parents and General Practitioners with End-of-Life Care in Adolescents and Young Adults with Cancer. AB - This study aims to analyze the experiences of Dutch bereaved parents and general practitioners (GPs) with palliative care of AYAs (18-35 years) in the terminal stage. Fifteen parents and nine GPs involved with nine deceased AYAs filled out questionnaires and were interviewed by telephone, respectively. In general, the parents were satisfied with the emotional care they themselves received and the medical care that their child received. The GPs were very satisfied with the cooperation with the palliative team. Gaps are present in the areas of symptom control, communication between hospital professionals and parents, aftercare, and transition between hospital and GP. PMID- 26812458 TI - A Review of Health Behaviors in Childhood and Adolescent Cancer Survivors: Toward Prevention of Second Primary Cancer. AB - PURPOSE: Survival of children and adolescents and young adults (AYAs) treated for cancer has increased with improved treatments. However, there is still an increased risk of second primary cancer (SPC) in the long term compared with the same-age population, especially related to treatments. The follow-up of this population and the prevention of SPC are important issues. Therefore, this study aimed to review the available literature on cancer risk factors (lifestyle and occupational exposures) in children and AYAs previously treated for cancer in order to identify interventions that might be implemented to improve healthy behaviors in this population. METHODS: PubMed was searched using the following terms: "cancer[Tiab] AND young adult[Tiab] or teen[Tiab] or childhood[Tiab] AND prevention[Tiab] AND survivors[Meshterm]." RESULTS: Twenty-seven articles were included. Children and AYA survivors of cancer have similar risk behaviors to their peers regarding tobacco, diet, and sun exposure. However, they have lower physical activity. Few studies on prevention strategies in this population were identified. Results of available studies remain inconclusive. No publications were found on occupational exposure and risk of second cancer. CONCLUSION: Children and AYAs treated for cancer are a population at risk and require specific effective prevention strategies. PMID- 26812459 TI - Metabolic Health in Childhood Cancer Survivors: A Longitudinal Study in a Long Term Follow-Up Clinic. AB - PURPOSE: Childhood cancer survivors (CCS) are at increased risk of metabolic dysfunction as a late effect of cancer treatment. However, pediatric metabolic syndrome (MetS) lacks a unified definition, limiting the diagnosis of MetS in CCS. This study evaluated individual metabolic health risk factors and potential areas for intervention in this at-risk population. METHODS: This single center, retrospective observational longitudinal study evaluated the metabolic health of all CCS attending an oncology long-term follow-up clinic at a university hospital in Sydney, Australia (January 2012-August 2014). Participants were 276 CCS (52.2% male; mean age 18.0 years; range 6.8-37.9 years), at least 5 years disease free with a broad spectrum of oncological diagnoses. Primary metabolic health risk factors included raised body mass index, hypertension, and hypertransaminasemia. Participants treated with cranial radiotherapy (n = 47; 17.0% of cohort) had additional biochemical variables analyzed: fasting glucose/insulin, HDL/LDL cholesterol, and triglycerides. RESULTS: Hypertension was common (19.0%), with male sex (p < 0.01) and being aged 18 years or above (p < 0.01) identified as risk factors. Cranial irradiation was a risk factor for overweight/obesity (47.8% in cranial radiotherapy-treated participants vs. 30.4%; p = 0.02). Hypertransaminasemia was more prevalent among participants treated with radiotherapy (15.6% vs. 7.3%; p = 0.03), and overweight/obese participants (17.6% vs. 8.2%; p = 0.04). CONCLUSION: Metabolic health risk factors comprising MetS are common in CCS, placing this population at risk of premature adverse cardiovascular consequences. Proactive surveillance and targeted interventions are required to minimize these metabolic complications, and a unified definition for pediatric MetS would improve identification and monitoring. PMID- 26812460 TI - Need and Use of Healthcare Services in Survivors of Hodgkin Lymphoma. AB - PURPOSE: Hodgkin lymphoma (HL) is the commonest cancer in adolescents and young adults (AYAs), aged 15-29 years. While the survival rate is high, many survivors experience adverse late effects of therapy. Yet, this age group in general makes limited use of health services. This study sought to determine whether the need for health services by HL survivors was mismatched to their health service utilization, as hypothesized a priori. METHODS: A population-based cohort of survivors (N = 43) younger than 39 years of age was sent a mailed survey for self assessment of need, as expressed in health-related quality of life (HRQOL), and utilization of health services by validated instruments; the Health Utilities Index and Health and Social Service Utilization Survey, respectively. Survivors who were AYAs at diagnosis were compared to children and older adults. RESULTS: AYAs had the lowest mean HRQOL score (0.79 on a scale of 0.00-1.00) compared to children (0.86) and older adults (0.94)-clinically meaningful differences. The difference in the single attribute score for cognition reached statistical significance (0.89 vs. 0.99 vs. 1.00, p = 0.02). AYAs also had lower mean overall annual costs for health services (CAN$601) than children (CAN$753) and older adults (CAN$936) did. CONCLUSIONS: Survivors of HL who were AYAs at diagnosis had a mismatch between high need for and low utilization of health services. Providers of healthcare to this population should be made aware of this discrepancy, and the survivors should be encouraged to seek the health services they need. PMID- 26812461 TI - Perceptions, Attributions, and Emotions Toward Endocrine Therapy in Young Women with Breast Cancer. AB - PURPOSE: The aims of this study were to describe symptoms attributed to endocrine therapy (ET) and perceptions of ET in a sample of young women with breast cancer and to explore whether these factors are associated with adherence to ET. METHODS: An online questionnaire was completed by 106 young women taking ET for hormone receptor-positive breast cancer. In addition to demographic and medical characteristics, the survey assessed symptom attribution, emotions, and perceptions related to ET. A supplemental survey measuring adherence to ET was completed by 82/106 women. Means, medians, and frequency distributions were calculated for continuous and categorical covariates, respectively. An exploratory analysis evaluated whether adherence was associated with patient characteristics and views. RESULTS: The mean age of respondents was 39 years (range 22-45 years). Two-thirds of women had stage 1 or 2 breast cancer. Women attributed an average of nine symptoms to ET; hot flashes, night sweats, and decreased libido were the most frequently attributed symptoms. Positive emotions toward ET were more common than negative emotions were, although only 48% of respondents believed that ET was essential. Women of higher financial status and those who reported more positive emotions toward ET reported greater adherence with ET. A significant difference in symptom attribution was not detected between less and more adherent respondents. CONCLUSIONS: Young women's views regarding ET may play an important role in determining adherence behavior. Given that young women have a higher risk of recurrence, some of which may be attributable to ET non-adherence, further work is needed to confirm these findings and determine whether interventions designed to modify young women's perceptions of ET could promote adherence. PMID- 26812462 TI - Young Adults' Access to Fertility Preservation Services at National Cancer Institute Community Oncology Research Program Minority/Underserved Community Sites: A Qualitative Study. AB - PURPOSE: This qualitative study aims to characterize the factors that influence access to fertility preservation (FP) resources and services after cancer diagnosis at NCI Community Oncology Research Program (NCORP) minority/underserved community sites, which serve patient populations comprising at least 30% racial/ethnic minorities or rural residents. METHODS: Phone interviews were conducted from 2014 to 2015 with interested and knowledgeable healthcare providers practicing at NCORP minority/underserved community sites, using a semi structured interview guide. Data were transcribed, de-identified, and analyzed using qualitative analysis software, Dedoose, to determine the most common themes in access to FP resources and services. RESULTS: Interviews were conducted with 10 board-certified physicians practicing at 10 of the 12 NCORP minority/underserved community sites; five respondents identified as oncologists, and five were reproductive endocrinology/infertility specialists (n = 4) or obstetricians/gynecologists (n = 1). Findings revealed highly variable access to FP resources at each site. Notable barriers to FP services were cost, time, provider education, lack of clinical guideline application, and perceptions among healthcare providers that negatively affect the discussion of options and risks with eligible patients. CONCLUSION: Clinical FP guidelines and resources for cancer patients and healthcare providers need to be better integrated into existing cancer networks that serve minority and underserved patient populations. Providers need more education regarding timely provision of FP services to all newly diagnosed cancer patients of reproductive age. PMID- 26812463 TI - Comparison of fetal and maternal heart rate measures using electrocardiographic and cardiotocographic methods. AB - PURPOSE: To determine the reliability at term of: (1) two methods of measuring fetal heart rate (HR), electrocardiographic (ECG, the 'gold standard') and cardiotocographic (CTG) and (2) two ECG methods of measuring maternal HR variability over relatively brief periods of time (s-min). METHODS: During 20 min of rest (N=39) and during 2 min of auditory stimulation (mother's recorded voice, n=19), fetal HR data were collected using an ECG (Monica AN24) and a Hewlett Packard Model 1351A CTG. Simultaneously, maternal HR data (n=37) were collected using the same ECG device (Monica AN24) and a second stand-alone cardiac monitor (Spacelab 514T cardiac monitor with a QRS detector). RESULTS: During 20 min of maternal rest, correlations of individual fetal CTG with ECG measures of HR at each second were moderate to high (r=.57-.97) for 77% of fetuses. Correlations of HR averaged over fetuses and over each of the 20 min were high (r=.93-.97); fetal HR averaged over 20 min varied between devices from 0.0 to 0.8 bpm. During 2 min of maternal voice presentation, correlations of fetal HR over each second were moderate to high (r=.54-.99) for 95% of fetuses and high (all rs=.99) when averaged across fetuses in 30s or 2 min epochs. Average fetal HR between devices over the 2 min voice varied from 0.0 to 0.6 bpm. Correlations and/or % agreement between the two ECG methods of measuring maternal HR were high. Average maternal HR over 10 min showed 81% of pairs with a difference of <= 1 bpm; correlations for HR variability measures varied from r=.89 to .97. CONCLUSIONS: Good reliability was demonstrated between individual spontaneous and auditory induced fetal CTG and ECG with high correlations when HR data were averaged over fetuses or in 30-120 s epochs. High reliability of maternal HR measures was obtained using two ECG devices. PMID- 26812464 TI - Smartphone-Based Urine Reagent Strip Test in the Emergency Department. AB - BACKGROUND: Although a smartphone could be used for a urine reagent strip test, few studies have reported on the reliability of the test in a clinical setting. The objective of our study was to access the smartphone-based urine reagent strip test in the clinical emergency department (ED). MATERIALS AND METHODS: We developed a smartphone-based urine reagent strip reader for a rapid and accurate screening of leukocyte esterase (LE) and nitrite (NIT) in urine. The developed reader was evaluated with the clinical urine samples (n = 81). The detection performance of the reader for LE and NIT was evaluated to assess reliability of the reader; turnaround times (TATs) for analysis and the time for the entire study procedure were also calculated to assess the efficiency of the reader. A photometric analyzer (model US-3100R Plus((r)); Eiken Chemical, Ltd., Tokyo, Japan) was used as a reference. RESULTS: The proposed reader showed high accuracy (85.2% for LE and 97.5% for NIT), exhibiting close agreement with the true values (kappa = 0.903 for LE; kappa = 1.000 for NIT). The reader also exhibited a lower median TAT for analysis than the photometric analyzer (3.0 min versus 33.0 min; p < 0.001). This reduction of TAT in the reader was even more evident considering the required time for delivery of urine samples for the photometric analyzer (3.0 min versus 62.0 min; p < 0.001). CONCLUSIONS: Our results demonstrated the clinical capability of a smartphone-based urine reagent strip test, and this reader is expected to enable a more rapid and reliable colorimetric test for screening of LE and NIT at the clinical setting and the point of care. PMID- 26812465 TI - Correction: Comprehensive Sieve Analysis of Breakthrough HIV-1 Sequences in the RV144 Vaccine Efficacy Trial. AB - [This corrects the article DOI: 10.1371/journal.pcbi.1003973.]. PMID- 26812466 TI - Feasibility of Xpert Ebola Assay in Medecins Sans Frontieres Ebola Program, Guinea. AB - Rapid diagnostic methods are essential in control of Ebola outbreaks and lead to timely isolation of cases and improved epidemiologic surveillance. Diagnosis during Ebola outbreaks in West Africa has relied on PCR performed in laboratories outside this region. Because time between sampling and PCR results can be considerable, we assessed the feasibility and added value of using the Xpert Ebola Assay in an Ebola control program in Guinea. A total of 218 samples were collected during diagnosis, treatment, and convalescence of patients. Median time for obtaining results was reduced from 334 min to 165 min. Twenty-six samples were positive for Ebola virus. Xpert cycle thresholds were consistently lower, and 8 (31%) samples were negative by routine PCR. Several logistic and safety issues were identified. We suggest that implementation of the Xpert Ebola Assay under programmatic conditions is feasible and represents a major advance in diagnosis of Ebola virus disease without apparent loss of assay sensitivity. PMID- 26812467 TI - Stimulation of Early Osteochondral Differentiation of Human Mesenchymal Stem Cells Using Binary Colloidal Crystals (BCCs). AB - A new surface based on self-assembly of two colloids into well-defined nanostructures, so-called binary colloidal crystals (BCCs), was fabricated for stem cell culture. The facile fabrication process are able to cover large surface areas (>3 cm-diameter, i.e. > 7 cm(2)) with ordered surface nanotopographies that is often a challenge particularly in biomaterials science. From our library, four different combinations of BCCs were selected using mixtures of silica, polystyrene and poly(methyl methacrylate) particles with sizes in the range from 100 nm to 5 MUm. Cell spreading, proliferation, and surface-induced lineage commitment of human adipose-derived stem cells (hADSCs) was studied using quantitative real time polymerase chain reaction (qRT-PCR) and immunostaining. The results showed that BCCs induced osteo- and chondro- but not adipo-gene expression in the absence of induction medium suggesting that the osteochondral lineage can be stimulated by the BCCs. When applying induction media, higher osteo- and chondro-gene expression on BCCs was found compared with tissue culture polystyrene (TCPS) and flat silica (Si) controls, respectively. Colony forming of chondrogenic hADSCs was found on BCCs and TCPS but not Si controls, suggesting that the differentiation of stem cells is surface-dependent. BCCs provide access to complex nanotopographies and chemistries, which can find applications in cell culture and regenerative medicine. PMID- 26812468 TI - Self-assembling oligothiophene-bolaamphiphiles for loading and controlled release of doxorubicin into living cells. AB - Design and synthesis of symmetric mannose-functionalized oligothiophenes is reported. Self-organization of these bolaamphiphiles in solution and in the solid state was investigated by optical and AFM experiments. Fluorescence measurements revealed efficient loading and pH-dependent release of the anti-cancer drug doxorubicin. Delivery and release of the active drug into viable A549 cells as well as chirality-dependent cellular toxicity of the bolaamphiphilic transporter were evident from in vitro experiments. PMID- 26812469 TI - AP92-like Crimean-Congo Hemorrhagic Fever Virus in Hyalomma aegyptium Ticks, Algeria. PMID- 26812470 TI - Bioactive Silver-Organic Networks Assembled from 1,3,5-Triaza-7-phosphaadamantane and Flexible Cyclohexanecarboxylate Blocks. AB - Three novel bioactive silver-organic networks, namely, the 2D polymer [Ag(MU3 PTA)(chc)]n.n(Hchc).2nH2O (1), the 3D bioMOF [Ag2(MU3-PTA)2(MU2-chdc)]n.5nH2O (2), and the 2D polymer [Ag2(MU2-PTA)2(MU4-H2chtc)]n.6nH2O (3), were constructed from 1,3,5-triaza-7-phosphaadamantane (PTA) and various flexible cyclohexanecarboxylic acids as building blocks {cyclohexanecarboxylic (Hchc), 1,4 cyclohexanedicarboxylic (H2chdc), and 1,2,4,5-cyclohexanetetracarboxylic (H4chtc) acid, respectively}. The obtained products 1-3 were fully characterized by IR and NMR spectroscopy, ESI-MS(+/-) spectrometry, elemental and thermogravimetric (TGA) analyses, and single-crystal and powder X-ray diffraction. Their structural diversity originates from distinct coordination modes of cyclohexanecarboxylate moieties as well as from the presence of unconventional N,N,P-tridentate or N,P bidentate PTA spacers. Topological classification of underlying metal-organic networks was performed, disclosing the hcb, 4,4L28, and a rare fsc-3,4-Pbcn-3 topology in 1, 2, and 3, respectively. Moreover, combination of aqueous solubility (S25 degrees C ~ 4-6 mg mL(-1)), air stability, and appropriate coordination environments around silver centers favors a release of bioactive Ag(+) ions by 1-3, which thus act as potent antibacterial and antifungal agents against Gram-positive (S. aureus) and Gram-negative (E. coli and P. aeruginosa) bacteria as well as a yeast (C. albicans). The best normalized minimum inhibitory concentrations (normalized MIC) of 10-18 (for bacterial strains) or 57 nmol mL( 1) (for a yeast strain) were achieved. Detailed ESI-MS studies were performed, confirming the relative stability of 1-3 in solution and giving additional insight on the self-assembly formation of polycarboxylate Ag-PTA derivatives and their crystal growth process. PMID- 26812471 TI - Photodissociation of acryloyl chloride at 193 nm: interpretation of the product energy distributions, and new elimination pathways. AB - The ground electronic state potential energy surface of acryloyl chloride, CH2CHC(O)Cl, has been mapped using an automated transition state search procedure. A total of 174 minima, 527 TSs, and 20 different dissociation channels have been found. Among others, three novel HCl elimination pathways, namely, a five-center mechanism and two three-body dissociations (leading to CO + HCl + HCCH) have been discovered. While the bimodal character of the experimental HCl rotational distributions was previously attributed to the presence of two competing channels, our dynamics simulations show that a single channel, the four center HCl elimination of CH2ClCHCO following a 1,3-Cl-shift of CH2CHC(O)Cl, displays a bimodal distribution in nearly prefect agreement with the experiment. Overall, our simulation results suggest that, as far as molecular elimination is concerned, this channel dominates in the 193 nm photodissociation of the molecule. The simulations also show evidence of non-IRC dynamics for this channel. PMID- 26812472 TI - Accuracy of Dengue Reporting by National Surveillance System, Brazil. PMID- 26812473 TI - Linking high resolution mass spectrometry data with exposure and toxicity forecasts to advance high-throughput environmental monitoring. AB - There is a growing need in the field of exposure science for monitoring methods that rapidly screen environmental media for suspect contaminants. Measurement and analysis platforms, based on high resolution mass spectrometry (HRMS), now exist to meet this need. Here we describe results of a study that links HRMS data with exposure predictions from the U.S. EPA's ExpoCastTM program and in vitro bioassay data from the U.S. interagency Tox21 consortium. Vacuum dust samples were collected from 56 households across the U.S. as part of the American Healthy Homes Survey (AHHS). Sample extracts were analyzed using liquid chromatography time-of-flight mass spectrometry (LC-TOF/MS) with electrospray ionization. On average, approximately 2000 molecular features were identified per sample (based on accurate mass) in negative ion mode, and 3000 in positive ion mode. Exact mass, isotope distribution, and isotope spacing were used to match molecular features with a unique listing of chemical formulas extracted from EPA's Distributed Structure-Searchable Toxicity (DSSTox) database. A total of 978 DSSTox formulas were consistent with the dust LC-TOF/molecular feature data (match score>=90); these formulas mapped to 3228 possible chemicals in the database. Correct assignment of a unique chemical to a given formula required additional validation steps. Each suspect chemical was prioritized for follow-up confirmation using abundance and detection frequency results, along with exposure and bioactivity estimates from ExpoCast and Tox21, respectively. Chemicals with elevated exposure and/or toxicity potential were further examined using a mixture of 100 chemical standards. A total of 33 chemicals were confirmed present in the dust samples by formula and retention time match; nearly half of these do not appear to have been associated with house dust in the published literature. Chemical matches found in at least 10 of the 56 dust samples include Piperine, N,N-Diethyl-m-toluamide (DEET), Triclocarban, Diethyl phthalate (DEP), Propylparaben, Methylparaben, Tris(1,3-dichloro-2-propyl)phosphate (TDCPP), and Nicotine. This study demonstrates a novel suspect screening methodology to prioritize chemicals of interest for subsequent targeted analysis. The methods described here rely on strategic integration of available public resources and should be considered in future non-targeted and suspect screening assessments of environmental and biological media. PMID- 26812474 TI - Mobius Aromatic Core-Modified Heterocyclic [20] Macrocycles (4.1.1) with a Protruding N-Methyl Pyrrole Ring. AB - Herein, we report the first synthesis of an unorthodox tripyrrane moiety from the regioselective beta-benzoylation of pyrrole and the acid-catalyzed condensation of the desired precursors. A [3+1] Mac Donald type condensation strategy for this tripyrrane has led to the exclusive isolation of two hitherto-unknown aromatic [20] heterocyclic macrocycles (4.1.1). PMID- 26812475 TI - Surface Enhanced Raman Scattering Based in Situ Hybridization Strategy for Telomere Length Assessment. AB - Assessing telomere length is of vital importance since telomere length is closely related with several fatal diseases such as atherosclerosis and cancer. Here, we present a strategy to assess/measure telomere length, that is, surface enhanced Raman scattering (SERS) based in situ hybridization (SISH). The SISH method uses two kinds of SERS nanoprobes to hybridize in situ with telomeres and centromeres, respectively. The telomere specific SERS nanoprobe is called the Telo-probe, while the centromere specific SERS nanoprobe is called the Centro-probe. They are composed of metal nanoparticles (NPs), Raman reporter molecules and specially designed DNA strands. With longer telomeres, more Telo-probes will hybridize with them, resulting in a stronger SERS signal. To exclude possible influence of the SERS intensity by external factors (such as the nanoprobe concentration, the cell number or different batches of nanoprobes), centromeres are used as the inner control, which can be recognized by Centro-probes. Telomere length is evaluated using a redefined telomere-to-centromere ratio (T/C ratio). The calculation method for T/C ratio in SISH method is more reliable than that in fluorescent in situ hybridization (FISH). In addition, unlike FISH method, the SISH method is insensitive to autofluorescence. Moreover, SISH method can be used to analyze single telomeres. These features make SISH an excellent alternative strategy for telomere length measurement. PMID- 26812476 TI - Clinico-Pathological Association of Delineated miRNAs in Uveal Melanoma with Monosomy 3/Disomy 3 Chromosomal Aberrations. AB - PURPOSE: To correlate the differentially expressed miRNAs with clinico pathological features in uveal melanoma (UM) tumors harbouring chromosomal 3 aberrations among South Asian Indian cohort. METHODS: Based on chromosomal 3 aberration, UM (n = 86) were grouped into monosomy 3 (M3; n = 51) and disomy 3 (D3; n = 35) by chromogenic in-situ hybridisation (CISH). The clinico pathological features were recorded. miRNA profiling was performed in formalin fixed paraffin embedded (FFPE) UM samples (n = 6) using Agilent, Human miRNA microarray, 8x15KV3 arrays. The association between miRNAs and clinico pathological features were studied using univariate and multivariate analysis. miRNA-gene targets were predicted using Target-scan and MiRanda database. Significantly dys-regulated miRNAs were validated in FFPE UM (n = 86) and mRNAs were validated in frozen UM (n = 10) by qRT-PCR. Metastasis free-survival and miRNA expressions were analysed by Kaplen-Meier analysis in UM tissues (n = 52). RESULTS: Unsupervised analysis revealed 585 differentially expressed miRNAs while supervised analysis demonstrated 82 miRNAs (FDR; Q = 0.0). Differential expression of 8 miRNAs: miR-214, miR-149*, miR-143, miR-146b, miR-199a, let7b, miR-1238 and miR-134 were studied. Gene target prediction revealed SMAD4, WISP1, HIPK1, HDAC8 and C-KIT as the post-transcriptional regulators of miR-146b, miR 199a, miR-1238 and miR-134. Five miRNAs (miR-214, miR146b, miR-143, miR-199a and miR-134) were found to be differentially expressed in M3/ D3 UM tumors. In UM patients with liver metastasis, miR-149* and miR-134 expressions were strongly correlated. CONCLUSION: UM can be stratified using miRNAs from FFPE sections. miRNAs predicting liver metastasis and survival have been identified. Mechanistic linkage of de-regulated miRNA/mRNA expressions provide new insights on their role in UM progression and aggressiveness. PMID- 26812477 TI - Morphological and morphometric study of protective effect of green tea in gentamicin-induced nephrotoxicity in rats. AB - AIMS: One of the most popular beverages worldwide, green tea, was investigated for its potential protective effect in a rat model of gentamicin-induced nephrotoxicity by monitoring functional and morphological changes in kidneys. MAIN METHODS: The study was conducted on four groups of rats: control group (C), treated with only gentamicin (GM), treated with only green tea (GT) and treated with both gentamicin and green tea (GT+GM). Kidney function, oxidant and antioxidant parameters of renal tissue, as well as histopathological studies were assessed. Morphometric analysis was used to quantify these histopathological changes. KEY FINDINGS: Gentamicin caused significant elevations in serum creatinine and urea and oxidative stress parameter (AOPP), while antioxidative enzyme catalase was significantly decreased. Histological sections of kidneys in GM group revealed necrosis of proximal tubules, vacuolation of cytoplasm and massive mononuclear inflammatory infiltrates in interstitium. Coadministration of green tea with gentamicin histologically showed renoprotective effect. Histological results were confirmed and quantified by morphometric analysis. Also in this group we measured ameliorated parameters of renal functions and antioxidative defense. SIGNIFICANCE: Regenerative potential of green tea after renal injury induced by gentamicin could be explained through the decrease of oxidative stress and lipid peroxidation. Green tea is a natural antioxidant, with many health promoting effects, widely available and in accordance to that affordable. Because of the established habits, people largely consume it as a beverage. It could be beneficial in the reduction of oxidative stress and changes caused by it primarily in renal tubules and interstitium. PMID- 26812478 TI - Determination of Sodium Tanshinone IIA Sulfonate in human plasma by LC-MS/MS and its application to a clinical pharmacokinetic study. AB - An assay based on protein precipitation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and validated for the quantitative analysis of Sodium Tanshinone IIA Sulfonate (STS) in human plasma. After the addition of dehydroepiandrosterone-D5-3-sulfate sodium salt (DHEAS-D5) as internal standard (IS) and formic acid, plasma samples were prepared by one-step protein precipitation with a mixture of acetonitrile and methanol. Isocratic mobile phase consisted of 0.4 mmol/L ammonium formate buffer (16 ppm formic acid)/acetonitrile (40/60, v/v) on a XSELECTTM HSS T3 column. Detection was performed on a triple-quadrupole mass spectrometer utilizing an electrospray ionization (ESI) interface operating in positive ion and selected reaction monitoring (SRM) mode with the precursor to product ion transitions m/z 373.3 >357.1 for STS and m/z 373.0->97.8 for the IS. Calibration curves of STS in human plasma were linear (r=0.9957-0.9998) over the concentration range of 2-1000 ng/mL with acceptable accuracy and precision. The lower limit of quantification in human plasma was 2 ng/mL. The validated LC-MS/MS method has been successfully applied to a pharmacokinetic study of STS in Chinese healthy male volunteers. PMID- 26812479 TI - Crystalline phase transition of ezetimibe in final product, after packing, promoted by the humidity of excipients: Monitoring and quantification by Raman spectroscopy. AB - Ezetimibe (EZT), in its anhydrous form, is a drug used for cholesterol and lipids reduction in blood plasma. The presence of EZT monohydrate in commercial tablets can change the solubility rate of the API, decreasing its activity. The objective of this work was to verify if the humidity present in the excipients could promote the phase transition from EZT anhydrous to hydrate. Initially the stability of the pure anhydrous form was monitored by Raman, at room temperature (23 degrees C) and relative humidity (75%). The MCR-ALS method showed that almost all EZT changed to hydrated form in 30 min. Then tablets of ezetimibe in the presence of its excipients were prepared and vacuum packed using a polyethylene film. Such tablet was monitored by Raman spectroscopy for 24h in order to quantify the mixture of the crystalline forms. A multivariate calibration model using Raman spectroscopy and Partial Least Square (PLS) regression was built, with validation and cross validation errors around 0.6% (wt/wt), for both crystalline forms, and R(2) higher than 0.96. The PLS model was used to quantify the crystalline mixture of ezetimibe in the monitored tablet, after 24h more than 70% of ezetimibe changed to the hydrated form. PMID- 26812480 TI - Force Nanoscopy as a Versatile Platform for Quantifying the Activity of Antiadhesion Compounds Targeting Bacterial Pathogens. AB - The development of bacterial strains that are resistant to multiple antibiotics has urged the need for new antibacterial therapies. An exciting approach to fight bacterial diseases is the use of antiadhesive agents capable to block the adhesion of the pathogens to host tissues, the first step of infection. We report the use of a novel atomic force microscopy (AFM) platform for quantifying the activity of antiadhesion compounds directly on living bacteria, thus without labeling or purification. Novel fullerene-based mannoconjugates bearing 10 carbohydrate ligands and a thiol bond were efficiently prepared. The thiol functionality could be exploited as a convenient handle to graft the multimeric species onto AFM tips. Using a combination of single-molecule and single-cell AFM assays, we demonstrate that, unlike mannosidic monomers, multivalent glycofullerenes strongly block the adhesion of uropathogenic Escherichia coli bacteria to their carbohydrate receptors. We expect that the nanoscopy technique developed here will help designing new antiadhesion drugs to treat microbial infections, including those caused by multidrug resistant organisms. PMID- 26812481 TI - Prolonged Distress of Parents After Early Preterm Birth. AB - OBJECTIVE: To examine how parents describe the distress of early preterm birth in the months and years after the infant's hospital discharge. DESIGN: Discourse analysis of in-depth interviews and photo elicitation. SETTING: Homes or cafes in the Pacific Northwest United States. PARTICIPANTS: Parents of premature infants born between 24 and 30 weeks gestation (N = 10) who experienced significant distress in and out of the hospital. Parents participated in the study when their children were between 15 months and 8 years old. METHODS: Participants described dealing with prematurity, emotional distress, and parenting in individual interviews and returned for second interviews in which they further described their distress using photographs. Data were analyzed using discourse analysis. RESULTS: Parents described preterm birth, hospitalization, and the aftermath as ongoing traumatic events. Discourses of distress included the Perfect Child, the Good Mother, and the Good Father. Parents used these discourses to reconcile the loss of an idealized birth and parenting after the birth of a premature child. Isolation and Medicalized Parenting were used to explain how parents struggled to interact within their social networks and to parent under challenging circumstances. CONCLUSION: Participants described their trauma and distress in ways not captured by psychiatric diagnoses such as depression and anxiety. Findings may help nurses be aware of the negative effects of preterm birth and respond to parents' emotional needs. PMID- 26812482 TI - On the Viability of Conspiratorial Beliefs. AB - Conspiratorial ideation is the tendency of individuals to believe that events and power relations are secretly manipulated by certain clandestine groups and organisations. Many of these ostensibly explanatory conjectures are non falsifiable, lacking in evidence or demonstrably false, yet public acceptance remains high. Efforts to convince the general public of the validity of medical and scientific findings can be hampered by such narratives, which can create the impression of doubt or disagreement in areas where the science is well established. Conversely, historical examples of exposed conspiracies do exist and it may be difficult for people to differentiate between reasonable and dubious assertions. In this work, we establish a simple mathematical model for conspiracies involving multiple actors with time, which yields failure probability for any given conspiracy. Parameters for the model are estimated from literature examples of known scandals, and the factors influencing conspiracy success and failure are explored. The model is also used to estimate the likelihood of claims from some commonly-held conspiratorial beliefs; these are namely that the moon-landings were faked, climate-change is a hoax, vaccination is dangerous and that a cure for cancer is being suppressed by vested interests. Simulations of these claims predict that intrinsic failure would be imminent even with the most generous estimates for the secret-keeping ability of active participants-the results of this model suggest that large conspiracies (>=1000 agents) quickly become untenable and prone to failure. The theory presented here might be useful in counteracting the potentially deleterious consequences of bogus and anti-science narratives, and examining the hypothetical conditions under which sustainable conspiracy might be possible. PMID- 26812483 TI - Electrochemistry of ferrocene derivatives on highly oriented pyrolytic graphite (HOPG): quantification and impacts of surface adsorption. AB - Cyclic voltammetry of three ferrocene derivatives - (ferrocenylmethyl)trimethylammonium (FcTMA(+)), ferrocenecarboxylic acid (FcCOOH), and ferrocenemethanol (FcCH2OH) - in aqueous solutions shows that the reduced form of the first two redox species weakly adsorbs onto freshly cleaved surfaces of highly oriented pyrolytic graphite (HOPG), with the fractional surface coverage being in excess of 10% of a monolayer at a bulk concentration level of 0.25 mM for both compounds. FcCH2OH was found to exhibit greater and stronger adsorption (up to a monolayer) for the same bulk concentration. The adsorption of FcTMA(+) on freshly cleaved surfaces of high quality (low step edge density) and low quality (high step edge density) HOPG is the same within experimental error, suggesting that the amount of step edges has no influence on the adsorption process. The amount of adsorption of FcTMA(+) is the same (within error) for low quality HOPG, irrespective of whether the surface is freshly cleaved or left in air for up to 12 hours, while - with aging - high quality HOPG adsorbs notably more FcTMA(+). The formation of an airborne contaminating film is proposed to be responsible for the enhanced entrapment of FcTMA(+) on aged high quality HOPG surfaces, while low quality surfaces appear less prone to the accumulation of such films. The impact of the adsorption of ferrocene derivatives on graphite for voltammetric studies is discussed. Adsorption is quantified by developing a theory and methodology to process cyclic voltammetry data from peak current measurements. The accuracy and applicability, as well as limits of the approach, are demonstrated for various adsorption isotherms. PMID- 26812484 TI - Emerging Disinfection Byproducts, Halobenzoquinones: Effects of Isomeric Structure and Halogen Substitution on Cytotoxicity, Formation of Reactive Oxygen Species, and Genotoxicity. AB - Halobenzoquinones (HBQs) are a structurally diverse class of water disinfection byproducts. Here, we report a systematic study on the effects of isomeric structure and the type and number of halogen substitutions of HBQs on their cytotoxicity, formation of reactive oxygen species (ROS), and genotoxicity. Dynamic responses and IC50 histograms were obtained using real-time cell analysis, clearly ranking the cytotoxicity of the HBQs in Chinese hamster ovary (CHO-K1) cells. Strong isomeric structure effects were shown with 2,5-HBQ isomers inducing greater cytotoxicity than their corresponding 2,6-HBQ isomers (P < 0.05). HBQ-halogen substitution groups also influence cytotoxicity, as cytotoxicity increases across the dihalogenated HBQs: iodo- > bromo- > chloro HBQs (P < 0.05). Determination of HBQ-induced ROS further supports isomeric structure and halogen substitution effects. HBQ-induced genotoxicity was shown as increased levels of 8-hydroxy-2'-deoxyguanosine and p53 protein. Pearson correlation analysis of the HBQ toxicity measurements with their physicochemical parameters demonstrates that dipole moment and the lowest unoccupied molecular orbital energy are two major structural influences on toxicity (r = -0.721 or 0.766, P < 0.05). Dipole moment also correlates with isomer toxicity. This study suggests that formation and occurrence of highly toxic iodo-HBQs and 2,5-HBQs warrant further investigation to fully assess the impact of HBQs in drinking water. PMID- 26812485 TI - Mediterranean Fin Whales (Balaenoptera physalus) Threatened by Dolphin MorbilliVirus. AB - During 2011-2013, dolphin morbillivirus was molecularly identified in 4 stranded fin whales from the Mediterranean Sea. Nucleoprotein, phosphoprotein, and hemagglutinin gene sequences of the identified strain were highly homologous with those of a morbillivirus that caused a 2006-2007 epidemic in the Mediterranean. Dolphin morbillivirus represents a serious threat for fin whales. PMID- 26812486 TI - Medicinal plants in Brazil: Pharmacological studies, drug discovery, challenges and perspectives. AB - This review article focuses on pre-clinical and clinical studies with some selected Brazilian medicinal plants in different areas of interest, conducted by research groups in Brazil and abroad. It also highlights the Brazilian market of herbal products and the efforts of Brazilian scientists to develop new phytomedicines. This review is divided into three sections. The section I describes the Brazilian large biodiversity and some attempts of Brazilian scientists to assess the pharmacological profile of most plant extracts or isolated active principles. Of note, Brazilian scientists have made a great effort to study the Brazilian biodiversity, especially among the higher plants. In fact, more than 10,000 papers were published on plants in international scientific journals between 2011 and 2013. This first part also discussed the main efforts to develop new medicines from plants, highlighting the Brazilian phytomedicines market. Despite the large Brazilian biodiversity, notably with the higher plants, which comprise over 45,000 species (20-22% of the total worldwide), and the substantial number of scientific publications on medicinal plants, only one phytomedicine is found in the top 20 market products. Indeed, this market is still only worth about 261 million American dollars. This represents less than 5% of the global Brazilian medicine market. The section II of this review focus on the use of Brazilian plant extract and/or active principles for some selected diseases, namely: central nervous systems disorders, pain, immune response and inflammation, respiratory diseases, gastrointestinal tract and metabolic diseases. Finally, section III discusses in more details some selected Brazilian medicinal plants including: Cordia verbenacea, Euphorbia tirucalli, Mandevilla velutina, Phyllanthus spp., Euterpe oleracea, Vitis labrusca, Hypericum caprifoliatum and Hypericum polyanthemum, Maytenus ilicifolia, Protium kleinii and Protium heptaphylium and Trichilia catigua. Most of these publications are preliminary and only report the effects of crude extracts, both in vitro and in vivo studies. Only very few studies have been dedicated to investigate the mechanisms of action of isolated compounds. Likewise, studies on safety (toxicology), pharmacokinetic, and especially on well conducted clinical trials are rare. In conclusion, in spite of the abundant Brazilian biodiversity and the thousands of academic publications on plants in international peer-reviewed scientific journals, few patents and medicines have been derived from such studies. Undoubtedly, great efforts must be made to improve the development of plant-derived medicine market in Brazil, especially by involving the partnership between academia and pharmaceutical companies. PMID- 26812487 TI - Toward FRP-Based Brain-Machine Interfaces-Single-Trial Classification of Fixation Related Potentials. AB - The co-registration of eye tracking and electroencephalography provides a holistic measure of ongoing cognitive processes. Recently, fixation-related potentials have been introduced to quantify the neural activity in such bi-modal recordings. Fixation-related potentials are time-locked to fixation onsets, just like event-related potentials are locked to stimulus onsets. Compared to existing electroencephalography-based brain-machine interfaces that depend on visual stimuli, fixation-related potentials have the advantages that they can be used in free, unconstrained viewing conditions and can also be classified on a single trial level. Thus, fixation-related potentials have the potential to allow for conceptually different brain-machine interfaces that directly interpret cortical activity related to the visual processing of specific objects. However, existing research has investigated fixation-related potentials only with very restricted and highly unnatural stimuli in simple search tasks while participant's body movements were restricted. We present a study where we relieved many of these restrictions while retaining some control by using a gaze-contingent visual search task. In our study, participants had to find a target object out of 12 complex and everyday objects presented on a screen while the electrical activity of the brain and eye movements were recorded simultaneously. Our results show that our proposed method for the classification of fixation-related potentials can clearly discriminate between fixations on relevant, non-relevant and background areas. Furthermore, we show that our classification approach generalizes not only to different test sets from the same participant, but also across participants. These results promise to open novel avenues for exploiting fixation-related potentials in electroencephalography-based brain-machine interfaces and thus providing a novel means for intuitive human-machine interaction. PMID- 26812488 TI - A cross-sectional study of carnitine deficiency and fatigue in pediatric cancer patients. AB - PURPOSE: Carnitine deficiency has been found in cancer patients and has been associated with fatigue. This study aimed to explore the prevalence of carnitine deficiency in pediatric cancer patients and its relationship with fatigue and other potential contributing factors. METHODS: Children with cancer or Langerhans cell histiocytosis who were receiving treatment or had completed therapy were eligible. Patients completed the Pediatric Functional Assessment of Chronic Illness-Fatigue, the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale, a numeric fatigue rating, and had carnitine levels obtained. Carnitine deficiency was defined as a total and/or free carnitine level less than normal for age or an acylcarnitine value higher than normal for age. RESULTS: Data from 142 children aged 8-17 were analyzed. Twenty-eight of 142 (19.7 %) had decreased total and 42.8 % (12/28) had decreased free carnitine levels. No patients had elevated acylcarnitine levels or elevated ratios. Patients with versus without carnitine deficiency differed by age (p = 0.043), treatment (p = 0.037), duration since last chemotherapy (p = 0.020), and body mass index (p = 0.010), but not fatigue, when all data were analyzed together. Yet, a negative relationship between fatigue and carnitine levels was found on a subgroup (off-therapy; fatigue worse than the norm). CONCLUSION: No significant association between fatigue and carnitine level was demonstrated when data from all patients were analyzed together; however, a significant yet unexpected relationship was found for patients who completed therapy and reported elevated fatigue. Given the small sample size, these results should be interpreted with caution. Future studies to explore impact upon excessive carnitine levels are warranted. PMID- 26812489 TI - The Risk of Dengue Virus Transmission in Dar es Salaam, Tanzania during an Epidemic Period of 2014. AB - BACKGROUND: In 2010, 2012, 2013 and 2014 dengue outbreaks have been reported in Dar es Salaam, Tanzania. However, there is no comprehensive data on the risk of transmission of dengue in the country. The objective of this study was to assess the risk of transmission of dengue in Dar es Salaam during the 2014 epidemic. METHODOLOGY/PRINCIPAL FINDINGS: This cross-sectional study was conducted in Dar es Salaam, Tanzania during the dengue outbreak of 2014. The study involved Ilala, Kinondoni and Temeke districts. Adult mosquitoes were collected using carbon dioxide-propane powered Mosquito Magnet Liberty Plus traps. In each household compound, water-holding containers were examined for mosquito larvae and pupae. Dengue virus infection of mosquitoes was determined using real-time reverse transcription polymerase chain reaction (qRT-PCR). Partial amplification and sequencing of dengue virus genome in infected mosquitoes was performed. A total of 1,000 adult mosquitoes were collected. Over half (59.9%) of the adult mosquitoes were collected in Kinondoni. Aedes aegypti accounted for 17.2% of the mosquitoes of which 90.6% were from Kinondoni. Of a total of 796 houses inspected, 38.3% had water-holding containers in their premises. Kinondoni had the largest proportion of water-holding containers (57.7%), followed by Temeke (31.4%) and Ilala (23.4%). The most common breeding containers for the Aedes mosquitoes were discarded plastic containers and tires. High Aedes infestation indices were observed for all districts and sites, with a house index of 18.1% in Ilala, 25.5% in Temeke and 35.3% in Kinondoni. The respective container indices were 77.4%, 65.2% and 80.2%. Of the reared larvae and pupae, 5,250 adult mosquitoes emerged, of which 61.9% were Ae. aegypti. Overall, 27 (8.18) of the 330 pools of Ae. aegypti were positive for dengue virus. On average, the overall maximum likelihood estimate (MLE) indicates pooled infection rate of 8.49 per 1,000 mosquitoes (95%CI = 5.72-12.16). There was no significant difference in pooled infection rates between the districts. Dengue viruses in the tested mosquitoes clustered into serotype 2 cosmopolitan genotype. CONCLUSIONS/SIGNIFICANCE: Ae. aegypti is the main vector of dengue in Dar es Salaam and breeds mainly in medium size plastic containers and tires. The Aedes house indices were high, indicating that the three districts were at high risk of dengue transmission. The 2014 dengue outbreak was caused by Dengue virus serotype 2. The high mosquito larval and pupal indices in the area require intensification of vector surveillance along with source reduction and health education. PMID- 26812491 TI - Correction: Growth and Reproduction of Glyphosate-Resistant and Susceptible Populations of Kochia scoparia. PMID- 26812490 TI - Addition of Arsenic Trioxide into Induction Regimens Could Not Accelerate Recovery of Abnormality of Coagulation and Fibrinolysis in Patients with Acute Promyelocytic Leukemia. AB - AIM: All-trans retinoic acid combined to anthracycline-based chemotherapy is the standard regimen of acute promyelocytic leukemia. The advent of arsenic trioxide has contributed to improve the anti-leukemic efficacy in acute promyelocytic leukemia. The objectives of the current study were to evaluate if dual induction by all-trans retinoic acid and arsenic trioxide could accelerate the recovery of abnormality of coagulation and fibrinolysis in patients with acute promyelocytic leukemia. METHODS: Retrospective analysis was performed in 103 newly-diagnosed patients with acute promyelocytic leukemia. Hemostatic variables and the consumption of component blood were comparably analyzed among patients treated by different induction regimen with or without arsenic trioxide. RESULTS: Compared to patients with other subtypes of de novo acute myeloid leukemia, patients with acute promyelocytic leukemia had lower platelet counts and fibrinogen levels, significantly prolonged prothrombin time and elevated D-dimers (P<0.001). Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification presented lower initial fibrinogen level than that of low-risk group (P<0.05). After induction treatment, abnormal coagulation and fibrinolysis of patients with acute promyelocytic leukemia was significantly improved before day 10. The recovery of abnormal hemostatic variables (platelet, prothrombin time, fibrinogen and D-dimer) was not significantly accelerated after adding arsenic trioxide in induction regimens; and the consumption of transfused component blood (platelet and plasma) did not dramatically change either. Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification had higher platelet transfusion demands than that of low-risk group (P<0.05). CONCLUSIONS: Unexpectedly, adding arsenic trioxide could not accelerate the recovery of abnormality of coagulation and fibrinolysis in acute promyelocytic leukemia patients who received all-trans retinoic acid combining chemotherapy. PMID- 26812492 TI - Amyloid-beta pathology and cerebral amyloid angiopathy are frequent in iatrogenic Creutzfeldt-Jakob disease after dural grafting. AB - QUESTIONS UNDER STUDY: Alzheimer-type amyloid-beta (Abeta) pathology was reported in brains of individuals developing iatrogenic Creutzfeldt-Jakob disease (iCJD) after treatment with human cadaveric growth hormone, and interpreted as evidence of human transmission of Abeta by the treatment. Here we investigated the prevalence of Abeta pathology in other instances of iCJD related to dura mater grafts. METHODS: By use of immunohistochemistry for Abeta, we investigated seven brains of patients (age range 28-63) who succumbed to iCJD after dural grafting, which had been applied by means of neurosurgery between 11 and 25 years before death. For control, we examined a series of 21 brains of age-matched (40-63 years) patients with sporadic CJD (sCJD) and an additional series of 81 sCJD cases (55-85 years) with the same methods. RESULTS: In five of seven iCJD brains, Abeta was deposited in meningeal vessels as congophilic amyloid angiopathy and brain parenchymal plaques. This was significantly (p <0.001) more frequent than in the age-matched sCJD controls and in the usual sCJD series. CONCLUSIONS: We conclude that congophilic amyloid angiopathy and brain parenchymal Abeta plaques are frequent in iCJD after dural grafting. The presence of Abeta pathology in young individuals is highly unusual and suggests a causal relationship to the dural grafts. Further studies will be needed to elucidate whether such pathology resulted from the seeding of Abeta aggregates from the grafts to host tissues. PMID- 26812493 TI - Insights from Theory and Experiment on the Photochromic spiro-Dihydropyrrolo Pyridazine/Betaine System. AB - We elucidated the photochromic spiro-4a,5-dihydropyrrolo[1,2-b]pyridazine/betaine (DPP/betaine) system by comparing state-of-the-art density functional theory calculations with nanosecond/millisecond UV-vis absorption spectroscopy, as well as steady-state absorption and cyclization kinetics. Time-dependent density functional theory calculations are employed to examine the transformations occurring after photoexcitation. This study shows that the photochromic spiro 4a,5-dihydropyrrolo[1,2-b]pyridazine and spiro-1,8a-dihydroindolizine (DHI) systems react according to similar pathways. However, notable differences exist. Although photoexcitation of the spiro-DPP system also leads to cis-betaines, which then isomerize to trans-betaines, we found two distinct classes of cis isomers (cis-betaine rotamer-1 and cis-betaine rotamer-2), which do not exist in spiro-1,8a-dihydroindolizine. Similar to our previous study on the spiro DHI/betaine system, a complicated potential-energy landscape between cis and trans isomers exists in the spiro-DPP system, consisting of a network of transition states and intermediates. Because the spiro-DPP/betaine is even more complicated than the spiro-DHI/betaine system, (substituted) photochromic systems featuring a 4a,5-dihydropyrrolo[1,2-b]pyridazine functional unit will require thorough in silico design to function properly as logical gates or in devices for information storage. PMID- 26812495 TI - The Color of Rice and the Chinese Paradox. PMID- 26812496 TI - Oxysterol-binding protein ORP3 rescues the Amyotrophic Lateral Sclerosis-linked mutant VAPB phenotype. AB - A mutation in VAPB causes a familial form of Amyotrophic Lateral Sclerosis. The mutant protein (VAPB-P56S) is aggregate prone and blocks retrograde traffic from the endoplasmic reticulum (ER) Golgi intermediate compartment (ERGIC) including trafficking to the nuclear envelope (NE). Here we report a morphological screen where overexpression of oxysterol binding protein-related protein-3 (ORP3) rescued the mutant VAPB phenotype. It resolved the mutant VAPB-induced membrane expansions, restored solubility of the mutant protein in non-ionic detergent, and restored trafficking of Emerin to the NE. Knockdown of ORP3 or VAPB increased the intracellular level of phosphatidylinositol 4-phosphate (PtdIns4P). Decreasing PtdIns4P levels by inhibiting its synthesis reduced the severity of the mutant VAPB-induced membrane expansions and restored Emerin trafficking to the NE. Thus, VAPB and its interacting partners cooperatively regulate protein trafficking through the ERGIC by modulating PtdIns4P levels. PMID- 26812494 TI - Biocatalytic portfolio of Basidiomycota. AB - Basidiomycota fungi have received little attention for applications in biocatalysis and biotechnology and remain greatly understudied despite their importance for carbon recycling, ecosystem functioning and medicinal properties. The steady influx of genome data has facilitated detailed studies aimed at understanding the evolution and function of fungal lignocellulose degradation. These studies and recent explorations into the secondary metabolomes have uncovered large portfolios of enzymes useful for biocatalysis and biosynthesis. This review will provide an overview of the biocatalytic repertoires of Basidiomycota characterized to date with the hope of motivation more research into the chemical toolkits of this diverse group of fungi. PMID- 26812497 TI - Vitamin A and insulin are required for the maintenance of hepatic stellate cell quiescence. AB - Transdifferentiation of vitamin A-storing hepatic stellate cells (HSCs) to vitamin A-depleted myofibroblastic cells leads to liver fibrosis. Vitamin A regulates lipid accumulation and gene transcription, suggesting that vitamin A is involved in the maintenance of HSC quiescence under a physiological condition. However, the precise mechanism remains elusive because there is no appropriate in vitro culture system for quiescent HSCs. Here, we show that treatment of quiescent HSCs with vitamin A partially maintained the accumulation of lipid droplets and expression of quiescent HSC markers (glial fibrillary acidic protein, peroxisome proliferator-activator receptor-gamma and CCAAT/enhancer binding protein-alpha) and also the expression of myofibroblastic markers (alpha smooth muscle actin, heat shock protein 47 and collagen type I). On the other hand, combined treatment with vitamin A and insulin sustained the characteristic of HSC quiescence and completely suppressed the expression of myofibroblastic markers through activation of the JAK2/STAT5 signaling pathway and increased expression of sterol regulatory element binding protein-1. These treated HSCs transdifferentiated to myofibroblastic cells under a culture condition with fetal bovine serum. The results suggest an important role of vitamin A and insulin in the maintenance of HSC quiescence under a physiological condition. PMID- 26812498 TI - Evidence for a rhizobia-induced drought stress response strategy in Medicago truncatula. AB - Drought stress hampers plant energy and biomass production; however it is still unknown how internal C:N balance and rhizobial symbiosis impact on plant response to water limitation. Here, the effect of differential optimal nitrogen nutrition and root nodule symbiosis on drought stress and rehydration responses of Medicago truncatula was assessed. Two groups of plants were nodulated with Sinorhizobium medicae or Sinorhizobium meliloti--differing in the performance of N fixation; the third group grew in a rhizobia-free medium and received mineral nitrogen fertilizer. In addition to growth analyses, physiological and molecular responses of the two systems were studied using ionomic, metabolomic and proteomic techniques. We found a significant delay in drought-induced leaf senescence in nodulated relative to non-nodulated plants, independent of rhizobial strain and uncoupled from initial leaf N content. The major mechanisms involved are increased concentrations of potassium and shifts in the carbon partitioning between starch and sugars under well-watered conditions, as well as the enhanced allocation of reserves to osmolytes during drought. Consequently, nodulated plants recovered more effectively from drought, relative to non-nodulated M. truncatula. Proteomic data suggest that phytohormone interactions and enhanced translational regulation play a role in increased leaf maintenance in nodulated plants during drought. PMID- 26812500 TI - Effects of low level lead exposure on associative learning and memory in the rat: Influences of sex and developmental timing of exposure. AB - Lead (Pb) exposure during development impairs a variety of cognitive, behavioral and neurochemical processes resulting in deficits in learning, memory, attention, impulsivity and executive function. Numerous studies have attempted to model this effect of Pb in rodents, with the majority of studies focusing on hippocampus associated spatial learning and memory processes. Using a different paradigm, trace fear conditioning, a process requiring coordinated integration of both the medial prefrontal cortex and the hippocampus, we have assessed the effects of Pb exposure on associative learning and memory. The present study examined both female and male long evans rats exposed to three environmentally relevant levels of Pb (150 ppm, 375 ppm and 750 ppm) during different developmental periods: perinatal (PERI; gestation-postnatal day 21), early postnatal (EPN; postnatal days 1-21) and late postnatal (LPN; postnatal days 1-55). Testing began at postnatal day 55 and consisted of a single day of acquisition training, and three post training time points (1, 2 and 10 days) to assess memory consolidation and recall. All animals, regardless of sex, developmental window or level of Pb exposure, successfully acquired conditioned-unconditioned stimulus association during training. However, there were significant effects of Pb-exposure on consolidation and memory recall at days 1-10 post training. In females, EPN and LPN exposure to 150 ppm Pb (but not PERI exposure) significantly impaired recall. In contrast, only PERI 150 ppm and 750 ppm-exposed males had significant recall deficits. These data suggest a complex interaction between sex, developmental window of exposure and Pb-exposure level on consolidation and recall of associative memories. PMID- 26812501 TI - Electrospun Nanofibrous Sheets for Selective Cell Capturing in Continuous Flow in Microchannels. AB - Electrospun nanofibrous meshes were surface-modified for selective capturing of specific cells from a continuous flow in PDMS microchannels. We electrospun nanofibrous mats composed of poly(epsilon-carprolactone) (PCL) and amine functionalized block copolymers composed of PCL and poly(ethylenimine) (PEI). A mixture of biotinylated PEG and blunt PEG was chemically tethered to the nanofibrous mats via the surface-exposed amines on the mat. The degree of biotinylation was fluorescently and quantitatively assayed for confirming the surface-biotinylation levels for avidin-specific binding. The incorporation level of avidin gradually increased when the blend ratio of biotinylated PEG on the mat increased, confirming the manipulated surfaces with various degree of biotinylation. Biotinylated cells were incubated with avidin-coated biotinylated mats and the specific binding of biotinylated cells was monitored in a microfluidic channel with a continuous flow of culture medium, which suggests efficient and selective capturing of the biotinylated cells on the nanofibrous mat. PMID- 26812499 TI - Integration and Validation of the Genome-Scale Metabolic Models of Pichia pastoris: A Comprehensive Update of Protein Glycosylation Pathways, Lipid and Energy Metabolism. AB - MOTIVATION: Genome-scale metabolic models (GEMs) are tools that allow predicting a phenotype from a genotype under certain environmental conditions. GEMs have been developed in the last ten years for a broad range of organisms, and are used for multiple purposes such as discovering new properties of metabolic networks, predicting new targets for metabolic engineering, as well as optimizing the cultivation conditions for biochemicals or recombinant protein production. Pichia pastoris is one of the most widely used organisms for heterologous protein expression. There are different GEMs for this methylotrophic yeast of which the most relevant and complete in the published literature are iPP668, PpaMBEL1254 and iLC915. However, these three models differ regarding certain pathways, terminology for metabolites and reactions and annotations. Moreover, GEMs for some species are typically built based on the reconstructed models of related model organisms. In these cases, some organism-specific pathways could be missing or misrepresented. RESULTS: In order to provide an updated and more comprehensive GEM for P. pastoris, we have reconstructed and validated a consensus model integrating and merging all three existing models. In this step a comprehensive review and integration of the metabolic pathways included in each one of these three versions was performed. In addition, the resulting iMT1026 model includes a new description of some metabolic processes. Particularly new information described in recently published literature is included, mainly related to fatty acid and sphingolipid metabolism, glycosylation and cell energetics. Finally the reconstructed model was tested and validated, by comparing the results of the simulations with available empirical physiological datasets results obtained from a wide range of experimental conditions, such as different carbon sources, distinct oxygen availability conditions, as well as producing of two different recombinant proteins. In these simulations, the iMT1026 model has shown a better performance than the previous existing models. PMID- 26812502 TI - Effect of Vitamin D Receptor Activators on Glomerular Filtration Rate: A Meta Analysis and Systematic Review. AB - BACKGROUND: Vitamin D receptor activators (VDRAs) can protect against mineral bone disease, but they are reported to elevate serum creatinine (SCr) and may also reduce glomerular filtration rate (GFR). METHODS: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) to evaluate the effect of VDRAs on kidney function and adverse events. MEDLINE, EMBASE, the Cochrane Controlled Trials Register were searched for RCTs that evaluate vitamin D receptor activators (alfacalcidol, calcitriol, doxercalciferol, falecalcitriol, maxacalcitol and paricalcitol) up to March 2015. RESULTS: We included 31 studies, all of which were performed between 1976 and 2015, which enrolled 2621 patients. Patients receiving VDRAs had lower eGFR (weighted mean difference WMD -1.29 mL/min /1.73 m2, 95% CI -2.42 to -0.17) and elevated serum creatinine (WMD 7.03 MUmol/L, 95% CI 0.61 to 13.46) in sensitivity analysis excluding studies with dropout rate more than 30%. Subgroup analysis of the 5 studies that not use SCr based measures did not indicated lower GFR in the VDRAs group(WMD -0.97 mL/min/1.73 m2, 95% CI -4.85 to 2.92). Compared with control groups, there was no difference in all-cause mortality (relative risk RR 1.41, 95% CI 0.58 to 3.80), cardiovascular disease (RR 0.84, 95% CI 0.42 to 1.71), and severe adverse events (RR 1.15, 95% CI 0.75 to 1.77) for the VDRAs groups. Episodes of hypercalcemia (RR 3.29, 95% CI 2.02 to 5.38) were more common in the VDRAs group than in the control group. CONCLUSIONS: Administration of VDRAs increased serum creatinine levels. Subgroup analysis of studies that did not use SCr-based measures did not indicate a lower GFR in the VDRA group. Future studies with non-SCr-based measures are needed to assess whether the mild elevations of serum creatinine are of clinical significance. PMID- 26812503 TI - Muscle Mass Index and Animal Source of Dietary Protein Are Positively Associated with Insulin Resistance in Participants of the NuAge Study. AB - OBJECTIVES: Contribute evidence towards the complex interrelationships of body composition, insulin sensitivity and protein intake independently from adiposity in an older population. DESIGN: This is a cross-sectional analysis of an existing dataset in which a literature-supported model linking together the variables of interest is tested using path analysis. SETTING: The loss of muscle mass has been implicated in the development of insulin resistance. We propose to test associations of muscle mass with insulin sensitivity and their respective associations with animal and vegetable sources of protein intake, independently from adiposity. PARTICIPANTS: Non-diabetic participants aged 68-82 years from the NuAge study with all available measures (n=441) were included. MEASUREMENTS: A model considering age, sex, chronic diseases, physical activity; smoking and sources of protein intake influencing body composition components and insulin sensitivity was created and tested with Path Analysis for their independent associations. Muscle mass index (MMI; kg/height in m2) and % body fat were derived from DXA and BIA. Insulin resistance was estimated by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score and physical activity by the Physical Activity Scale for the Elderly (PASE) questionnaire. Protein intakes were obtained from three non-consecutive 24h-diet recalls. RESULTS: In the final model, direct positive associations were observed between HOMA-IR score and MMI (beta=0.42; 95%CI: 0.24; 0.6) and % body fat (beta=0.094; 95%CI: 0.07; 0.11). There were no direct associations between animal protein intake and MMI or with HOMA-IR. There was a significant direct negative association between plant protein intake and MMI (beta= -0.068; 95%CI: -0.13; -0.003) and significant indirect associations mediated through MMI and % body fat between HOMA-IR and animal protein intake (beta=0.0321; 95%CI: 0.01; 0.05), as well as plant protein intake (beta= -0.07; 95%CI: -0.1; 0.0). CONCLUSIONS: Our final model indicated that MMI and HOMA score were significantly positively associated. Protein intake sources were related to HOMA-IR score differently through MMI and % body fat, respectively. PMID- 26812504 TI - Does Low Body Mass Index Matter? Relationship between Body Mass Index and Subjective Well-Being among Long-Lived Women over 95 Years of Age. AB - OBJECTIVES: To examine the relationship between body mass index (BMI) and subjective well-being (SWB) among long-lived women over 95 years of age and evaluate whether this relationship is mediated by functional ability. DESIGN: Retrospective cohort study. SETTING: Data from the Rugao longevity cohort, a population-based study in Rugao, China. PARTICIPANTS: A sample of 342 long-lived women (mean age 97.4 +/- 2.1, range 95-107) whose SWB and other covariates were available were included in this study. MEASUREMENTS: BMI was calculated as weight in kilograms divided by height in meters-squared (kg/m(2)). SWB was measured by life satisfaction (LS), positive affect (PA), negative affect (NA) and affect balance (AB). Functional ability was assessed by the Katz Index of Activities of Daily Living (ADL). RESULTS: According to BMI classification standards for China, the underweight group had lower levels of LS than the normal and overweight groups (28.62 vs. 30.51 and 31.57, respectively; p<.05). Correlation analysis showed that BMI was significantly related to LS (r = 0.166, p<.01). The strength of the BMI and LS association was diminished when ADL was included in the general linear regression models. Mediation analysis revealed that ADL mediated this relationship (effect size = 22.6%). We did not observe significant associations of BMI with other SWB components (PA, NA, and AB). CONCLUSION: For long-lived women, low BMI, rather than elevated BMI, is an indicator of poor psychological well-being. The findings call for public health awareness about low body weight in long-lived women, especially in those with physical disabilities when focusing on quality of life. PMID- 26812505 TI - Dietary Features and Blood Pressure among 18-88-Year-Old Residents in an Island Population in China. AB - OBJECTIVES: Dietary recommendations to reduce blood pressure (BP) have been widely disseminated and residents who live on islands have unique dietary characteristics. Here, we identified associations between dietary intake and BP levels among island residents in China. DESIGN: Cross-sectional study. SETTING: The Changhai islands, which is an important island county in China. PARTICIPANTS: A total of 876 residents, 18-88 years old, of Changhai county. MEASUREMENTS: Dietary intake and BP measurements were assessed using standardized questionnaires and protocols, respectively. Dietary intake was compared across BP categories and linear regression analyses were performed between dietary intake and systolic blood pressure (SBP) and diastolic blood pressure (DBP). RESULTS: Participants previously diagnosed with hypertension consumed less salt than those with undiagnosed high BP (p < 0.01). After exclusion of participants previously diagnosed with hypertension, salt and meat consumption were positively and linearly associated with both SBP (p < 0.01 and < 0.001, respectively) and DBP (p = 0.03 and < 0.01, respectively), whereas consumption of marine products was inversely associated with SBP (p = 0.047). Mixed edible oil and edible oil consumption were associated with SBP (p < 0.01) and DBP (p = 0.021), respectively. In the multiple linear regression model, meat intake was positively associated with both SBP and DBP (beta = 0.139, p < 0.001; beta = 0.066, p = 0.047, respectively), whereas consumption of marine products was inversely associated with SBP (beta = -0.102, p <0.001), while mixed edible oil was associated with SBP (beta = 0.062, p = 0.03). CONCLUSION: Adherence to nutritional recommendations can be improved among hypertensive patients, even those aware of their conditions. In the general island population, eating habits regarding salt, meat, edible oil consumption, and use of mixed edible oil increased the risk of hypertension onset, whereas marine products were found to decrease this risk. PMID- 26812506 TI - Screening for Malnutrition in Community Dwelling Older Japanese: Preliminary Development and Evaluation of the Japanese Nutritional Risk Screening Tool (NRST). AB - BACKGROUND: Early and effective screening for age-related malnutrition is an essential part of providing optimal nutritional care to older populations. OBJECTIVE: This study was performed to evaluate the adaptation of the original SCREEN II questionnaire (Seniors in the Community: Risk Evaluation for Eating and Nutrition, version II) for use in Japan by examining its measurement properties and ability to predict nutritional risk and sarcopenia in community-dwelling older Japanese people. The ultimate objective of this preliminary validation study is to develop a license granted full Japanese version of the SCREEN II. PARTICIPANTS: The measurement properties and predictive validity of the NRST were examined in this cross-sectional study of 1921 community-dwelling older Japanese people. MEASUREMENTS: Assessments included medical history, and anthropometric and serum albumin measurements. Questions on dietary habits that corresponded to the original SCREEN II were applied to Nutritional Risk Screening Tool (NRST) scoring system. Nutritional risk was assessed by the Geriatric Nutrition Risk Index (GNRI) and the short form of the Mini-Nutritional Assessment (MNA-SF). Sarcopenia was diagnosed according to the criteria of the European Working Group on Sarcopenia in Older People. RESULTS: The nutritional risk prevalences determined by the GNRI and MNA-SF were 5.6% and 34.7%, respectively. The prevalence of sarcopenia was 13.3%. Mean NRST scores were significantly lower in the nutritionally at-risk than in the well-nourished groups. Concurrent validity analysis showed significant correlations between NRST scores and both nutritional risk parameters (GNRI or MNA-SF) and sarcopenia. The areas under the receiver operating characteristic curves (AUC) of NRST for the prediction of nutritional risk were 0.635 and 0.584 as assessed by GNRI and MNA-SF, respectively. AUCs for the prediction of sarcopenia were 0.602 (NRST), 0.655 (age-integrated NRST), and 0.676 (age and BMI-integrated NRST). CONCLUSIONS: These results indicate that the NRST is a promising screening tool for the prediction of malnutrition and sarcopenia in community-dwelling older Japanese people. Further development of a full Japanese version of the SCREEN II is indicated. PMID- 26812507 TI - Differences in Medical and Life-style Risk Factors for Malnutrition in Limited Resource Older Adults in a Rural U.S. State: A Descriptive Study. AB - OBJECTIVES: Medical and life-style factors are associated with malnutrition in older adults. This study assessed the presence of these risk factors in limited resource, community-dwelling older adults to inform the development of a nutrition education interventions. DESIGN: Quantitative descriptive study. SETTING: A total of 24 randomly selected congregate nutrition sites (where limited-resource older adults can receive one hot meal/day, five days/week) in the rural state of South Carolina, USA. PARTICIPANTS: Data were collected from 477 older adults (of the 407 who reported race, 219 were African American and 171 were White). MEASUREMENTS: Extension Educators who work for the Cooperative Extension Service (a formalized educational outreach system associated with some U.S. universities) read aloud a 27-item instrument designed to assess risk factors for malnutrition. Response frequencies were tabulated and chi-square tests were performed using SAS 9.3. RESULTS: More African Americans reported having a chronic illness or condition (81.2 vs. 68.3%; p=0.003), eating alone (66.2 vs. 53.6%; p=0.012), having a refrigerator that sometimes did not keep food cold (31.8 vs. 8.4%; p<0.0001), and sometimes not having enough money to buy food (38.9 vs. 18.5%; p<0.0001) compared to White older adults. CONCLUSION: Rural older adults who attend congregate nutrition sites, especially African Americans, could be at risk for malnutrition due to health status and food preparation related factors. Evidence-based, tailored programs are needed to minimize malnutrition among limited-resource older adults living in rural areas in the U.S. PMID- 26812509 TI - The Impact of a Home-Based Computerized Cognitive Training Intervention on Fall Risk Measure Performance in Community Dwelling Older Adults, a Pilot Study. AB - OBJECTIVES: Cognitive intervention studies have reported improvements in various domains of cognition as well as a transfer effect of improved function post training. Despite the availability of web based cognitive training programs, most intervention studies have been performed under the supervision of researchers. Therefore, the purpose of this study was to first, examine the feasibility of a six week home based computerized cognitive training (CCT) program in a group of community dwelling older adults and, second, to determine if a CCT program which focused on set shifting, attention, and visual spatial ability impacted fall risk measure performance. DESIGN: This pilot study used a pretest/posttest experimental design with randomization by testing site to an intervention or control group. PARTICIPANTS: Community dwelling older adults (mean age = 74.6 years) participated in either the control (N=25) or the intervention group (N=19). INTERVENTION: Intervention group subjects participated in 6 weeks of home based CCT 3x/week for an average of 23 minutes/session, using an online CCT program. MEASUREMENTS: Comparisons of mean scores on three measures of physical function (usual gait speed, five times sit to stand, timed up and go) were completed at baseline and week 7. RESULTS: Following the completion of an average of 18 sessions of CCT at home with good adherence (86%) and retention (92%) rates, a statistically significant difference in gait speed was found between groups with an average improvement of 0.14 m/s in the intervention group. CONCLUSION: A home based CCT program is a feasible approach to targeting cognitive impairments known to influence fall risk and changes in gait in older adults. PMID- 26812508 TI - Consumption of Dairy Products and Cognitive Functioning: Findings from the SU.VI.MAX 2 Study. AB - OBJECTIVES: Research concerning the link between dairy product intake and cognition is scant while experimental studies suggest links through various biological mechanisms. This study's objective was to examine the cross-time associations of total and specific dairy product consumption with cognitive performance in aging adults. We also explored compliance with dairy intake recommendations in France. DESIGN: The study was based on the "Supplementation en Vitamines et Mineraux Antioxydants" randomized trial (SU.VI.MAX, 1994-2002) and the SU.VI.MAX 2 observational follow-up study (2007-2009). SETTING: A general population cohort in France. PARTICIPANTS: N=3,076 participants included in both the SU.VI.MAX and SU.VI.MAX 2 studies. MEASUREMENTS: Dairy product consumption was estimated using repeated 24h records (1994-1996; mean=10 records, SD=3). Cognitive performance was assessed by neuropsychologists after an average of 13 years post-baseline via a battery of six validated tests. Mean age at the time of the cognitive function evaluation was 65.5 (SD=4.6) years. Principal component analysis revealed factors for verbal memory and working memory. Associations of energy-adjusted dairy product consumption and compliance with the respective dietary guidelines with subsequent cognitive impairment were examined using ANCOVA, providing mean differences (95% confidence intervals, CI) according to tertiles (T), adjusted for confounders including overall dietary patterns. RESULTS: Total dairy product consumption was not associated with cognitive function. However, milk intake was negatively associated with verbal memory performance: mean difference T3 versus T1= -0.99 (-1.83, -0.15). Among women, consuming more than the recommended amount of dairy was negatively associated with working memory performance: excess versus adequate = -1.52 (-2.93, -0.11). CONCLUSION: Our results indicate that dairy products consumption and especially compliance with dietary guidelines regarding dairy product intake are differentially associated with performance in specific cognitive domains after a comprehensive adjustment for lifestyle factors, health status markers and dietary patterns. Further longitudinal research is needed given the limited data available. PMID- 26812510 TI - Association of Long-Term Dietary Fat Intake, Exercise, and Weight with Later Cognitive Function in the Finnish Diabetes Prevention Study. AB - OBJECTIVES: To investigate associations of long-term nutrient intake, physical activity and obesity with later cognitive function among the participants in the Finnish Diabetes Prevention Study, in which a lifestyle intervention was successful in diabetes prevention. DESIGN: An active lifestyle intervention phase during middle age (mean duration 4 years) and extended follow-up (additional 9 years) with annual lifestyle measurements, followed by an ancillary cognition assessment. SETTING: 5 research centers in Finland. PARTICIPANTS: Of the 522 middle-aged, overweight participants with impaired glucose tolerance recruited to the study, 364 (70%) participated in the cognition assessment (mean age 68 years). MEASUREMENTS: A cognitive assessment was executed with the CERAD test battery and the Trail Making Test A on average 13 years after baseline. Lifestyle measurements included annual clinical measurements, food records, and exercise questionnaires during both the intervention and follow-up phase. RESULTS: Lower intake of total fat (p=0.021) and saturated fatty acids (p=0.010), and frequent physical activity (p=0.040) during the whole study period were associated with better cognitive performance. Higher BMI (p=0.012) and waist circumference (p=0.012) were also associated with worse performance, but weight reduction prior to the cognition assessment predicted worse performance as well (decrease vs. increase, p=0.008 for BMI and p=0.002 for waist). CONCLUSIONS: Long-term dietary fat intake, BMI, and waist circumference have an inverse association with cognitive function in later life among people with IGT. However, decreases in BMI and waist prior to cognitive assessment are associated with worse cognitive performance, which could be explained by reverse causality. PMID- 26812511 TI - Homocysteine and Mild Cognitive Impairment: Are These the Tools for Early Intervention in the Dementia Spectrum? AB - Dementia, being a neurodegenerative disease, has devastating consequences not just for the ailing but also for the carers as it has a tremendous negative impact on the quality of life. The pathophysiology of dementia commences far earlier than its diagnosis. Mild cognitive impairment (MCI) is a stage prior to definite dementia. The progression from MCI to dementia is insidious with no definite demarcation, thus making diagnosis clinically difficult at an early stage. This paper attempts to throw light on the epidemiology, risk factors and the aetiopathogenesis of MCI. It further attempts to elaborate on the rate of conversion of MCI to definite dementia and the factors influencing the same. Many established as well as probable, modifiable as well as non-modifiable risk factors influence the progress of MCI to definite dementia. Homocysteine, a sulphur containing amino-acid has been identified as a probable risk factor for the dementia spectrum. Various existing clinical evidences and biological plausibility towards probable link between homocysteine and dementia are discussed in this paper. B vitamin mediated homocysteine reduction and cognitive outcomes demonstrate mixed results. This review attempts to evaluate hyperhomocysteinaemia and MCI as a brain risk marker and assess their potential for future research with a view to attempt early intervention. PMID- 26812513 TI - Impact of Nutritional Status and Sleep Quality on Hospital Utilisation in the Oldest Old with Heart Failure. AB - OBJECTIVES: To describe three-year trends in nutritional status and sleep quality and their impact on hospital utilisation in the oldest old (80 +) with heart failure (HF). DESIGN: Single-centred longitudinal observational study. SETTING: South-eastern Sweden. PARTICIPANTS: 90 elderly (80+) with objectively verified HF. MEASUREMENTS: Baseline data from the Mini Nutritional Assessment (MNA) and on sleep quality were collected through structured interviews following the HF diagnosis (n=90) and at a three-year follow-up (n=41). Data on hospital utilisation during the three years following the HF diagnosis were also collected. RESULTS: Nineteen percent of the participants were found to have impaired nutritional status, a condition that increased hospital utilisation by four bed days per year. A majority (85%) had impaired sleep quality, but no impact on hospital utilisation was found. Nutritional status and sleep quality were stable over the three-year period. CONCLUSION: In the oldest old with HF, impaired nutritional status and impaired sleep quality are already common at HF diagnosis. Impaired nutritional status increases hospital utilisation significantly. Therefore, it is of supreme importance to systematically evaluate nutritional status and sleep quality in the oldest old when they are diagnosed with HF, as well as to take action if impairments are present. PMID- 26812512 TI - Fish Oil Supplementation Increases Event-Related Posterior Cingulate Activation in Older Adults with Subjective Memory Impairment. AB - OBJECTIVES: To determine the effects of long-chain omega-3 (LCn-3) fatty acids found in fish oil, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cortical blood oxygen level-dependent (BOLD) activity during a working memory task in older adults with subjective memory impairment. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Academic medical center. PARTICIPANTS: Healthy older adults (62-80 years) with subjective memory impairment, but not meeting criteria for mild cognitive impairment or dementia. INTERVENTION: Fish oil (EPA+DHA: 2.4 g/d, n=11) or placebo (corn oil, n=10) for 24 weeks. MEASUREMENTS: Cortical BOLD response patterns during performance of a sequential letter n-back working memory task were determined at baseline and week 24 by functional magnetic resonance imaging (fMRI). RESULTS: At 24 weeks erythrocyte membrane EPA+DHA composition increased significantly from baseline in participants receiving fish oil (+31%, p <= 0.0001) but not placebo (-17%, p=0.06). Multivariate modeling of fMRI data identified a significant interaction among treatment, visit, and memory loading in the right cingulate (BA 23/24), and in the right sensorimotor area (BA 3/4). In the fish oil group, BOLD increases at 24 weeks were observed in the right posterior cingulate and left superior frontal regions during memory loading. A region-of-interest analysis indicated that the baseline to endpoint change in posterior cingulate cortex BOLD activity signal was significantly greater in the fish oil group compared with the placebo group during the 1-back (p=0.0003) and 2-back (p=0.0005) conditions. Among all participants, the change in erythrocyte EPA+DHA during the intervention was associated with performance in the 2-back working memory task (p = 0.01), and with cingulate BOLD signal during the 1-back (p = 0.005) with a trend during the 2-back (p = 0.09). Further, cingulate BOLD activity was related to performance in the 2-back condition. CONCLUSION: Dietary fish oil supplementation increases red blood cell omega-3 content, working memory performance, and BOLD signal in the posterior cingulate cortex during greater working memory load in older adults with subjective memory impairment suggesting enhanced neuronal response to working memory challenge. PMID- 26812514 TI - Effectiveness of Food-Based Fortification in Older People. A Systematic Review and Meta-Analysis. AB - BACKGROUND: Early intervention with nutritional support has been found to stop weight loss in older people malnourished or at risk of malnutrition. Enriched food could be a more attractive alternative to improve meals, than conventional oral nutritional supplements. AIMS: To determine the effectiveness of food-based fortification to prevent risk of malnutrition in elderly patients in community or institutionalized elderly patients. METHODS: A systematic review was conducted of randomized controlled trials, quasi-experimental, and interrupted time series including a longitudinal analysis. PARTICIPANTS: Elderly patients who are institutionalized, hospitalized or community-dwelling, with a minimum average age of 65 years. All type of patient groups, with the exception of people in critical care, or those who were recovering from cancer treatment, were included. INTERVENTION: Studies had to compare food-based fortification against alternatives. Studies that used oral nutritional supplementation such as commercial sip feeds, vitamin or mineral supplements were excluded. The search was conducted in Cochrane, CINAHL, PubMed, EMBASE, LILACS, and Cuiden. An independent peer review was carried out. RESULTS: From 1011 studies obtained, 7 were included for the systematic review, with 588 participants. It was possible to perform meta-analysis of four studies that provided results on caloric and protein intake. Food-based fortification yielded positive results in the total amount of ingested calories and protein. Nevertheless, due to the small number of participants and the poor quality of some studies, further high quality studies are required to provide reliable evidence. IMPLICATIONS FOR PRACTICE: Despite the limited evidence, due to their simplicity, low cost, and positive results in protein and calories intake, simple dietary interventions based on the food-based fortification or densification with protein or energy of the standard diet could be considered in patients at risk of malnutrition. PMID- 26812516 TI - FRAIL-NH Predicts Outcomes in Long Term Care. AB - BACKGROUND/OBJECTIVES: To investigate the predictive validity of the short, simple FRAIL-NH frailty screening tool in the long term care population and to then compare the predictive validity with the frailty index (FI) for 6-month adverse health outcomes. DESIGN: Retrospective study using the Minimum Data Set (MDS) 3.0 and chart review from June-December 2014. SETTING: Two Long Term Care Facilities in Saint Louis, MO. PARTICIPANTS: 270 patients ages >= 65 years old residing in long term care. MEASUREMENTS: Frailty was measured using the FRAIL-NH and Frailty Index (FI) criteria. Adverse outcomes measured at 6-month follow-up included falls, hospitalizations, and hospice enrollment/mortality. RESULTS: Based on screening tool used frailty prevalence was 48.7% for FRAIL-NH and 30.3% for FI. The FRAIL-NH pre-frail (Adjusted Odds Ratio [AOR]=2.62; 95% Confidence Interval [CI]=1.25-5.54; p=0.11) classification was associated with 6 month risk of falling and mortality/hospice enrollment was associated with the frail classification, AOR=3.96 (1.44-10.87, p=0.007). Combining the pre-frail and frail categories both measures predicted 6 month mortality with the FRAIL-NH being the strongest predictor (AOR=3.36; 95%CI=1.26-8.98; p=0.016) and the FI was a more modest predictor with an AOR of 2.28; 95%CI=1.01-5.15; p=0.047. When directly comparing the FRAIL-NH to the FI, the FRAIL-NH pre-frail were at increased risk of falling, AOR=2.42 (1.11-5.92, p=0.027) and the FRAIL-NH frail were at increased risk of hospice enrollment/death, OR=3.25 (1.04- 10.86) p=0.044. CONCLUSION: In comparison to the FI, the FRAIL-NH preformed just as well at screening for frailty and was a slightly better predictor of adverse outcomes. The FRAIL-NH is a brief, easy-to-administer frailty screening tool appropriate for long term care patients and predicts increased risk of falls in the pre-frail and mortality/hospice enrollment in the frail. PMID- 26812515 TI - Effects of Nutritional Supplements on Muscle Mass and Activities of Daily Living in Elderly Rehabilitation Patients with Decreased Muscle Mass: A Randomized Controlled Trial. AB - OBJECTIVE: To investigate the effects of nutritional intervention with resistance training on skeletal muscle mass in elderly patients with disabilities in a convalescent rehabilitation setting. DESIGN: A randomized controlled trial. (UMIN Clinical Trials Registry ID: UMIN000006238). SETTING: A rehabilitation hospital. PARTICIPANTS: 39 elderly patients with decreased skeletal muscle mass in an inpatient convalescence rehabilitation unit. INTERVENTIONS: A combination of resistance training plus nutritional supplementation (R/N group) or resistance training alone (R group). The training and supplementation were conducted essentially from the patient's admission to discharge (2-6 months). OUTCOME MEASURES: The patients were evaluated at the time of admission and at the end of the intervention for skeletal muscle mass (calf circumference [CC] as a primary outcome, and arm circumference [AC]), hand grip strength (HG), Mini-Nutritional Assessment-Short Form (MNA(r)-SF) score, serum albumin level (Alb), body mass index (BMI), and activities of daily living (ADL) as represented by the Barthel Index (BI) score. RESULTS: Significant treatment effects were seen for CC, AC, BI, Alb in the R/N group compared to the R group. A mean treatment effect of 3.2 (95%CI: 2.0-4.4) was seen in CC, 1.4 (95%CI: 0.8-2.1) was seen in AC, 11.2 (95%CI: 0.5-21.8) was seen in BI, 0.3 (95%CI: 0.1-0.5) was seen in Alb. CONCLUSION: The results of this study suggest that nutritional intervention added to resistance training during convalescent rehabilitation may improve skeletal muscle mass and activities of daily living. PMID- 26812518 TI - Oral Submucous Fibrosis Secondary to Iron Deficiency Anemia: A Case Report, Etiopathogenesis and Management. AB - Oral submucous fibrosis (OSMF) is a premalignant condition that has received considerable attention in the recent past because of its chronic debilitating and resistant nature. Over the past decades, dental researchers have reported overwhelming evidence about various etiological factors of OSMF. It has been the subject of controversy ever since Schwartz first described the condition in 1952. Areca nut is considered the primary etiology along with other local irritants like capsaicin, pungent and spicy food, nutritional deficiency, defective iron metabolism, collagen metabolic disorder and genetic predisposition. Association of iron deficiency anemia and OSMF is very sparse in literature. Here, we present a case report of a 58 year old male patient where the patient presented with OSMF where iron deficiency anemia was found to be the main etiological factor. PMID- 26812517 TI - Nutritional State Predicts All-Cause Death Independent of Comorbidities in Geriatric Patients with Coronary Artery Disease. AB - OBJECTIVE: To explore whether nutritional risk is associated with poor outcomes independent of complicated clinical status in older patients with coronary artery disease (CAD). DESIGN: Cohort study. SETTING: Patients referred for coronary angiography in West China Hospital, Sichuan University, China. PARTICIPANTS: 1772 patients with angiographic documented CAD whose age was above 65 years. MEASUREMENTS: Nutritional state was appraised using geriatric nutritional risk index (GNRI). Nutritional risk was defined as the GNRI below 98. The event rate of all-cause death was observed among patients with nutritional risk and those without. RESULTS: During a median follow-up period of 27 months, 224 patients died. Multivariate Cox regression analysis showed that nutritional risk was associated with all-cause death (adjusted hazard ratio 1.99; 95% confidence interval 1.35-2.95; P=0.001). Subgroup analysis verified the association between nutritional risk and death among patients with distinct clinical features, comorbidities, and medication. There was no interaction between nutritional risk and clinical characteristics with regard to all-cause death. CONCLUSION: Nutritional state is independently associated with the risk of all-cause death in geriatric patients with CAD. Whether nutritional support in appropriate patients improves clinical outcomes deserves further investigation. PMID- 26812519 TI - Risk of Unplanned Emergency Department Readmission after an Acute-Care Hospital Discharge among Geriatric Inpatients: Results from the Geriatric EDEN Cohort Study. AB - OBJECTIVES: The study aims 1) to examine whether items of the brief geriatric assessment (BGA) or their combinations predicted the risk of unplanned emergency department readmission after an acute care hospital discharge among geriatric inpatients, and 2) to determine whether BGA could be used as a prognostic tool for unplanned emergency department readmission. METHODS: A total of 312 older patients (mean age, 84.6 +/- 5.4 years; 64.1% female) hospitalized in acute care wards after an emergency department visit were recruited in this observational prospective cohort study and separated into 2 groups based on the occurrence or not of an unplanned emergency department readmission during a 12-month follow-up period after their hospital discharge. A 6-item BGA was performed at emergency department admission before the discharge to acute care wards. Information on incident unplanned emergency department readmission was prospectively collected by phone call and by consulting the hospital registry. Several combinations of items of BGA identifying three levels of risk of unplanned emergency department readmission (i.e., low risk, intermediate risk and high risk) were examined. RESULTS: The unplanned emergency department readmission was more frequently associated with a temporal disorientation (P=0.004). Area under receiver operating characteristic curves of unplanned emergency department readmission based on BGA items and their combinations ranged from 0.53 to 0.61. The best predictor of unplanned emergency department readmission was the temporal disorientation (hazard ratio>1.65, P<0.035), which defined the high-risk group. Inpatients classified in high-risk group of unplanned emergency department readmission were more frequently readmitted to emergency department than those in intermediate- and low-risk groups (P log Rank <0.004). Prognostic values for unplanned emergency department readmission of items and their combinations were poor with sensitivity below 67%, specificity ranging from 36.4 to 53.7, and positive likelihood ratio below 1.4. CONCLUSIONS: The items of BGA and their combinations were significant risk factors for unplanned emergency department readmission, but their prognostic value was poor. PMID- 26812521 TI - Letter to the editor: RE: Comments Referring to the Article "Comprehensive Nutritional Status in Sarco-Osteoporotic Older Fallers". PMID- 26812520 TI - Validity, Reliability and Feasibility of Tools to Identify Frail Older Patients in Inpatient Hospital Care: A Systematic Review. AB - BACKGROUND: The objective of this study is to identify and review screening tools for frailty in older adults admitted to inpatient hospital care with respect to their validity, reliability and feasibility. METHODS: Studies were identified through systematically searching PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase and PsycINFO and screening reference lists till June 2014. Papers dealing with screening tools aimed at identifying frail older patients in in-hospital care, and including information about validity, reliability or feasibility, were included in the review. The quality of the included studies was critically appraised via the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). RESULTS: From the originally identified 2001 studies 32 studies met the inclusion criteria, in which 16 screening tools were presented. The screening tools showed different characteristics with respect to the number of items, the method of administration and the domains included. The most frequently studied tools with respect to predictive validity were the Identification Seniors At Risk (ISAR) and Triage Risk Stratification Tool (TRST). Studies retrieved poorer information about reliability and feasibility. Overall sensitivity was fairly good. The ISAR, ISAR-HP (Identification Seniors At Risk Hospitalized Patients) and Multidimensional Prognostic Index (MPI) generally had the best sensitivity. CONCLUSIONS: Many screening tools are available for daily practice. These tools to identify frail older patients in inpatient hospital care could be useful. For no tool, however, is clear evidence available yet regarding validity, reliability and feasibility. The overall sensitivity of the included screening tools was fairly good, whereas information on reliability and feasibility was lacking for most tools. In future research more attention should be given to the latter items. PMID- 26812522 TI - Rates of organ donation in a UK tertiary cardiac arrest centre following out-of hospital cardiac arrest. AB - AIM: To ascertain the rate of successful organ donation (OD) within patients who sustained an out of hospital cardiac arrest (OHCA) with initial return of spontaneous circulation (ROSC) and survival to hospital admission, but whom subsequently do not survive to hospital discharge. METHODS: A retrospective audit of ambulance service and hospital databases from January 2010 to January 2015 was undertaken in a United Kingdom tertiary-referral regional cardiac arrest centre. Crude denominator data for cardiac arrests was obtained from the regional ambulance service; the ICU database was interrogated for OHCA patient admissions and outcomes. Patients who died were cross-referenced against the local Organ Donation service database. RESULTS: Five hundred and fourteen {514} patients were admitted to ICU following OHCA over this five year period. Two hundred and forty one {241} patients (47%) survived to hospital discharge and 273 (53%) died of whom 106 (39%) were referred to a Specialist Nurse for Organ Donation (SNOD). The conversion rate after the family was approached was 64%. Twenty-eight {28} patients proceeded to donation and 25 patients (24%) successfully donated at least one organ. On average, a patient proceeding to donation provided 1.9 organs. CONCLUSIONS: A proactive, systematic approach to OD in OHCA patients can provide a good conversion rate and substantial number of donors. Most donations occur after death from circulatory criteria. There is a positive socio-economic benefit with nearly L4m in savings to the health service within the next 5 years potentially being realised during this period by liberating patients from dialysis. PMID- 26812524 TI - Assessing Progress towards Public Health, Human Rights, and International Development Goals Using Frontier Analysis. AB - Indicators to measure progress towards achieving public health, human rights, and international development targets, such as 100% access to improved drinking water or zero maternal mortality ratio, generally focus on status (i.e., level of attainment or coverage) or trends in status (i.e., rates of change). However, these indicators do not account for different levels of development that countries experience, thus making it difficult to compare progress between countries. We describe a recently developed new use of frontier analysis and apply this method to calculate country performance indices in three areas: maternal mortality ratio, poverty headcount ratio, and primary school completion rate. Frontier analysis is used to identify the maximum achievable rates of change, defined by the historically best-performing countries, as a function of coverage level. Performance indices are calculated by comparing a country's rate of change against the maximum achievable rate at the same coverage level. A country's performance can be positive or negative, corresponding to progression or regression, respectively. The calculated performance indices allow countries to be compared against each other regardless of whether they have only begun to make progress or whether they have almost achieved the target. This paper is the first to use frontier analysis to determine the maximum achievable rates as a function of coverage level and to calculate performance indices for public health, human rights, and international development indicators. The method can be applied to multiple fields and settings, for example health targets such as cessation in smoking or specific vaccine immunizations, and offers both a new approach to analyze existing data and a new data source for consideration when assessing progress achieved. PMID- 26812523 TI - Alterations in Monocyte Phenotypes and Functions after a Hip Fracture in Elderly Individuals: A 6-Month Longitudinal Study. AB - BACKGROUND: Healthy elderly individuals are particularly prone to catastrophic events at any moment of their lives. One stressful event for individuals aged 65 and older is a fall that results in a fracture of the hip (HF). HF causes a state of inflammation that may affect immune responses. In this connection, we have reported that HF induced alterations in neutrophil functions. OBJECTIVE: To assess the impact of HF on classical (cM), intermediate (iM) and non-classical (ncM) monocyte subsets. METHODS: Distribution, functions (chemotaxis, phagocytosis, superoxide production and cytokine production), phenotype and activation (NF-x03BA;B and PI3K) were evaluated in monocyte subsets before surgery and 6 weeks and 6 months after the event. RESULTS: The distribution of cM and ncM was unchanged, but iM transiently increased before surgery. Sustained increases (iM response to CCL2 and CX3CL1) and decreases (cM and ncM response to CCL2) in chemotaxis were observed. Phagocytosis and superoxide production were impaired in cM but not in iM or ncM. Sustained expression of HLA-DR occurred in cM but not in iM and ncM. Sustained decreased expression of CD11b occurred only in ncM. Sustained decreases (cM and ncM) and increases (iM) in CCR2 expression were observed. An elevated expression of CX3CR1 was found only in iM. cM produced elevated quantities of TNFalpha. There was a transient oxidative burst of production before surgery in iM and a sustained decrease in ncM. IL-10 production was severely impaired in cM and decreased in iM prior to surgery. Sustained activation (cM), inhibition (ncM) and transient activation (iM) of NF-x03BA;B were observed. Activation of PI3K was severely impaired in cM and ncM but was sustained in iM. CONCLUSION: HF had more impact on cM and ncM functions than on iM. HF triggered a switch in cM functions from phagocytic to inflammatory elevated TNFalpha-producing cells. These changes may impact clinical outcomes of HF with respect to inflammation, opportunistic infections and physical recovery. PMID- 26812525 TI - Specific Reaction Patterns to Distinct Positive Emotional Cues Related to Incentive Motivation in Dependence of the Taq1A-Polymorphism: Molecular Genetic Associations of Early and Late Event-Related Potentials. AB - BACKGROUND/AIMS: Early and late event-related potential (ERP) responses, representing early subconscious and late motivational processes, were recorded for positive emotional words related to 'wanting' and 'liking', in dependence of the dopamine-related Taq1A genotype (ANKK1/DRD2). Research suggests that 'wanting' as opposed to 'liking' is related to dopaminergic processes. Therefore, it was hypothesized that risk allele carriers of the Taq1A polymorphism exhibit late ERP changes in reaction to words representing incentive motivation, i.e. 'wanting' (word categories 'lust' and 'anticipation'), but not to words representing 'liking' ('closeness'). METHODS: Seventy-two male participants performed an emotional-word Stroop task during EEG recording and were genotyped according to the Taq1A polymorphism of ANKK1/DRD2. RESULTS: Positive emotional words related to anticipation and lust revealed blunted responses in the late positive potential (LPP) in carriers of the A1 allele, an effect absent in response to 'liking'-related words. These differences were not evident in the earlier posterior negativity (EPN). CONCLUSION: As no differences in dependence of the Taq1A genotype were observed in reaction to 'wanting'- and 'liking' related words in the EPN, but merely in the LPP, it can be assumed that incentive motivational stimuli only modify motivation-related ERP responses in carriers of the A1 allele of the Taq1A polymorphism, indicating the role of dopamine in late ERP components. PMID- 26812526 TI - A Puzzle Unsolved: Failure to Observe Different Effects of God and Religion Primes on Intergroup Attitudes. AB - Religious priming has been found to have both positive and negative consequences, and recent research suggests that the activation of God-related and community related religious cognitions may cause outgroup prosociality and outgroup derogation respectively. The present research sought to examine whether reminders of God and religion have different effects on attitudes towards ingroup and outgroup members. Over two studies, little evidence was found for different effects of these two types of religious primes. In study 1, individuals primed with the words "religion", "God" and a neutral control word evaluated both ingroup and outgroup members similarly, although a marginal tendency towards more negative evaluations of outgroup members by females exposed to religion primes was observed. In study 2, no significant differences in attitudes towards an outgroup member were observed between the God, religion, and neutral priming conditions. Furthermore, the gender effect observed in study 1 did not replicate in this second study. Possible explanations for these null effects are discussed. PMID- 26812527 TI - Trimethylphosphine-Assisted Surface Fingerprinting of Metal Oxide Nanoparticle by (31)P Solid-State NMR: A Zinc Oxide Case Study. AB - Nano metal oxides are becoming widely used in industrial, commercial and personal products (semiconductors, optics, solar cells, catalysts, paints, cosmetics, sun cream lotions, etc.). However, the relationship of surface features (exposed planes, defects and chemical functionalities) with physiochemical properties is not well studied primarily due to lack of a simple technique for their characterization. In this study, solid state (31)P MAS NMR is used to map surfaces on various ZnO samples with the assistance of trimethylphosphine (TMP) as a chemical probe. As similar to XRD giving structural information on a crystal, it is demonstrated that this new surface-fingerprint technique not only provides qualitative (chemical shift) but also quantitative (peak intensity) information on the concentration and distribution of cations and anions, oxygen vacancies and hydroxyl groups on various facets from a single deconvoluted (31)P NMR spectrum. On the basis of this technique, a new mechanism for photocatalytic *OH radical generation from direct surface-OH oxidation is revealed, which has important implications regarding the safety of using nano oxides in personal care products. PMID- 26812528 TI - Plasmonic Nanogels for Unclonable Optical Tagging. AB - We demonstrate the fabrication of novel functional gel coatings with randomized physical and chemical patterns that enable dual encoding ability to realize unclonable optical tags. This design is based on swelling-mediated massive reconstruction of an ultrathin responsive gelatinous polymer film uniformly adsorbed with plasmonic nanostructures into a randomized network of interacting folds, resulting in bright electromagnetic hotspots within the folds. We reveal a strong correlation between the topology and near-field electromagnetic field enhancement due to the intimate contact between two plasmonic surfaces within the folds, each of them representing a unique combination of local topography and chemical distribution caused by the formation of electromagnetic hotspots. Because of the efficient trapping of the Raman reporters within the uniquely distributed electromagnetic hotspots, the surface enhanced Raman scattering enhancement from the morphed plasmonic gel was found to be nearly 40 times higher compared to that from the pristine plasmonic gel. Harnessing the nondeterministic nature of the folds, the folded plasmonic gel can be employed as a multidimensional (with dual topo-chemical encoding) optical taggant for prospective anticounterfeiting applications. Such novel optical tags based on the spontaneous folding process are virtually impossible to replicate because of the combination of nondeterministic physical patterns and chemical encoding. PMID- 26812530 TI - Kinetic Energy of Hydrocarbons as a Function of Electron Density and Convolutional Neural Networks. AB - We demonstrate a convolutional neural network trained to reproduce the Kohn-Sham kinetic energy of hydrocarbons from an input electron density. The output of the network is used as a nonlocal correction to conventional local and semilocal kinetic functionals. We show that this approximation qualitatively reproduces Kohn-Sham potential energy surfaces when used with conventional exchange correlation functionals. The density which minimizes the total energy given by the functional is examined in detail. We identify several avenues to improve on this exploratory work, by reducing numerical noise and changing the structure of our functional. Finally we examine the features in the density learned by the neural network to anticipate the prospects of generalizing these models. PMID- 26812529 TI - Formation of M-Like Intermediates in Proteorhodopsin in Alkali Solutions (pH >= ~8.5) Where the Proton Release Occurs First in Contrast to the Sequence at Lower pH. AB - Proteorhodopsin (PR) is an outward light-driven proton pump observed in marine eubacteria. Despite many structural and functional similarities to bacteriorhodopsin (BR) in archaea, which also acts as an outward proton pump, the mechanism of the photoinduced proton release and uptake is different between two H(+)-pumps. In this study, we investigated the pH dependence of the photocycle and proton transfer in PR reconstituted with the phospholipid membrane under alkaline conditions. Under these conditions, as the medium pH increased, a blue shifted photoproduct (defined as Ma), which is different from M, with a pKa of ca. 9.2 was produced. The sequence of the photoinduced proton uptake and release during the photocycle was inverted with the increase in pH. A pKa value of ca. 9.5 was estimated for this inversion and was in good agreement with the pKa value of the formation of Ma (~ 9.2). In addition, we measured the photoelectric current generated by PRs attached to a thin polymer film at varying pH. Interestingly, increases in the medium pH evoked bidirectional photocurrents, which may imply a possible reversal of the direction of the proton movement at alkaline pH. On the basis of these findings, a putative photocycle and proton transfer scheme in PR under alkaline pH conditions was proposed. PMID- 26812531 TI - African Buffalo Movement and Zoonotic Disease Risk across Transfrontier Conservation Areas, Southern Africa. AB - We report on the long-distance movements of subadult female buffalo within a Transfrontier Conservation Area in Africa. Our observations confirm that bovine tuberculosis and other diseases can spread between buffalo populations across national parks, community land, and countries, thus posing a risk to animal and human health in surrounding wildlife areas. PMID- 26812532 TI - Guest Editorial: Have We Lost Sight Of The Original Vision For Smep And Mbr? PMID- 26812533 TI - Autonomy Or The Autonomies? Trait Consistency And Situation Specificity. AB - Reports of a series of item and factor analyses of a number of sentence completion and multiple-choice measures of autonomy in children are presented. Factors suggested in early versions of the tests were strengthened in later versions. Various factor analyses were performed on 2041 children averaging age 12, using four separate and progressive versions of the measure. Autonomy was differentiated into independence when faced with obstacles, in the face of parental pressure, in the face of peer pressure, and in traumatic situations. The results are discussed as supporting the interactionist position in the situation specific and trans-situational trait-consistency controversy. PMID- 26812534 TI - Transformation Of Axes In Interbattery Factor Analysis. AB - Tucker's interbattery factor analysis model is briefly reviewed. The various transformational alternatives possible with the model are delineated, and those resulting in identical orientations of the factors -- in the interbattery factor spaces for the two batteries -- are identified and developed further. Transformation in the interbattery context is developed using the Harris-Kaiser logic of oblique factor solutions by orthonormal transformations, and methods for obtaining the necessary common orthonormal transformation matrix are discussed. PMID- 26812535 TI - Inefficient Redundancy. AB - Two articles on canonical correlation are criticized as erroneous, Wood (1972) and Nicewander & Wood (1974). In both instances, the errors would have been avoided had the authors been required to offer both the mathematical basis of their contributions and illustrative worked examples. PMID- 26812536 TI - Common Misconceptions Concerning The Analysis Of Covariance. AB - Four misconceptions about the requirements for proper use of analysis of covariance (ANCOVA) are examined by means of Monte Carlo simulation. Conclusions are that ANCOVA does not require covariates to be measured without error, that ANCOVA can be used effectively to adjust for initial group differences that result from nonrandom assignment which is dependent on observed covariate scores, that ANCOVA does not provide unbiased estimates of true treatment effects where initial group differences are due to nonrandom assignment which is dependent on the true latent covariable if the covariate contains measurement error, and that ANCOVA requires no assumption concerning the equality of within-groups and between-groups regression. Where treatments actually influence covariate scores, the hypothesis tested by ANCOVA concerns a weighted combination of effects on covariate and dependent variables. PMID- 26812537 TI - A Maximum Likelihood Solution To The Errors In Variables And Errors In Equations Model. AB - This article provides a maximum likelihood estimation procedure for a linear model with errors in variables. Warren, et al, provide a least squares procedure for the same problem but which may be shown to be a special case of the more general approach suggested here. Also unlike the least squares approach, this formulation permits tests of the independence of measurement errors as well as the equality of measurement units. The importance of testing these assumptions is related to various definitions as well as estimation methods for reliability. PMID- 26812538 TI - Exploring Relationships Among Multiple Data Sets. AB - This paper has two related aims. First, some conceptual and mathematical relationships are discussed among alternative procedures for analyzing multiple data sets, including: inter-battery factor analysis (Tucker, 1958; Kristof, 1967), multiple regression, canonical correlation, generalized canonical correlation (Horst, 1965; Kettenring, 1971), longitudinal factor analysis (Corballis and Traub, 1970), and multiple set factor analysis (Golding and Seidman, 1974; Jackson, 1975). To motivate the comparison, each technique is related to a principal components model. The second aim is to describe an exploratory data analysis strategy for integrating the relative advantages of canonical correlation and multiple set factor analysis. When considering two data sets, the testing of statistical significance of appropriate linear combinations is emphasized, together with a further transformation to enhance substantive interpretation of the data. PMID- 26812539 TI - A Longitudinal Factor Model For Studying Change In Ability Structure. AB - Models of the Longitudinal Factor Analysis type were designed to describe the development of ability structure between the ages 10 and 13. The parameters of the models were estimated by the LISREL program (Joreskog & van Thillo, 1973). The sample comprised 375 girls and 353 boys who were tested at age 10 and retested at age 13 with six ability tests and two achievement tests. The results indicate that verbal, inductive, and spatial abilities can be described as developing fairly independently of each other between the ages 10 and 13. At age 13, but not at age 10, two subfactors of the inductive factor could be differentiated. The unique variances show a marked decrease between age 10 and age 13. Consequently the factors, and the relationships between factors, explain more of the variance of the response variates at age 13 than at age 10. PMID- 26812540 TI - On Weighted G Analysis. AB - An analytic method for discriminating between clinical subgroups is introduced. It is based on a weighted G index and is therefore called weighted G analysis. In this analysis group weights for the various items are determined, after which a Q analysis is run on the analysis group. Scores in the factors for imagined delegates of the clinical subgroups are computed, after which scores of the individuals in a validation group are computed. Using a distance-based placement system, the persons in the validation group are placed into subgroups. For a specific set of empirical data with normals and schizophrenics as subgroups, 31 of 32 subjects were placed correctly. PMID- 26812541 TI - The Semistandardized Regression Coefficient. AB - The semistandardized regression coefficient is presented for combining unstandardized and standardized variables into a single regression equation. Equations, interpretations, and an example are given for applying the coefficients to multivariate data. PMID- 26812542 TI - Membrane Protein Mobility and Orientation Preserved in Supported Bilayers Created Directly from Cell Plasma Membrane Blebs. AB - Membrane protein interactions with lipids are crucial for their native biological behavior, yet traditional characterization methods are often carried out on purified protein in the absence of lipids. We present a simple method to transfer membrane proteins expressed in mammalian cells to an assay-friendly, cushioned, supported lipid bilayer platform using cell blebs as an intermediate. Cell blebs, expressing either GPI-linked yellow fluorescent proteins or neon-green fused transmembrane P2X2 receptors, were induced to rupture on glass surfaces using PEGylated lipid vesicles, which resulted in planar supported membranes with over 50% mobility for multipass transmembrane proteins and over 90% for GPI-linked proteins. Fluorescent proteins were tracked, and their diffusion in supported bilayers characterized, using single molecule tracking and moment scaling spectrum (MSS) analysis. Diffusion was characterized for individual proteins as either free or confined, revealing details of the local lipid membrane heterogeneity surrounding the protein. A particularly useful result of our bilayer formation process is the protein orientation in the supported planar bilayer. For both the GPI-linked and transmembrane proteins used here, an enzymatic assay revealed that protein orientation in the planar bilayer results in the extracellular domains facing toward the bulk, and that the dominant mode of bleb rupture is via the "parachute" mechanism. Mobility, orientation, and preservation of the native lipid environment of the proteins using cell blebs offers advantages over proteoliposome reconstitution or disrupted cell membrane preparations, which necessarily result in significant scrambling of protein orientation and typically immobilized membrane proteins in SLBs. The bleb-based bilayer platform presented here is an important step toward integrating membrane proteomic studies on chip, especially for future studies aimed at understanding fundamental effects of lipid interactions on protein activity and the roles of membrane proteins in disease pathways. PMID- 26812543 TI - Ambient UV-B exposure reduces the binding of ofloxacin with bacterial DNA gyrase and induces DNA damage mediated apoptosis. AB - Ofloxacin (OFLX) is a broad spectrum antibiotic, which generates photo-products under sunlight exposure. Previous studies have failed to explain the attenuated anti-bacterial activity of OFLX. The study was extended to explore the unknown molecular mechanism of photogenotoxicity on human skin cell line (HaCaT) under environmental UV-B irradiation. Photochemically OFLX generates ROS and caused 2' dGuO photodegradation. We have addressed the binding affinity of OFLX and its photo-products against DNA gyrase. Significant free radical generation such as (1)O2, O2(*-) and (*)OH reduces antioxidants and demonstrated the ROS mediated OFLX phototoxicity. However, the formation of micronuclei and CPDs showed photogenotoxic potential of OFLX. OFLX induced cell cycle arrest in sub-G1 peak. OFLX triggers apoptosis via permeabilization of mitochondrial membrane with the downregulation of anti-apoptotic Bcl-2 and caspase-3 whereas, upregulation of pro apoptotic Bax and Cyto-C proteins. Our study illustrated that binding affinity of OFLX photo-products with DNA gyrase was mainly responsible for the attenuated antimicrobial activity. It was proved through molecular docking study. Thus, study suggests that sunlight exposure should avoid by drug users especially during peak hours for their safety from photosensitivity. Clinicians may guide patients regarding the safer use of photosensitive drugs during treatment. PMID- 26812544 TI - Discoveries, target identifications, and biological applications of natural products that inhibit splicing factor 3B subunit 1. AB - Covering: 1992 to 2015The natural products FR901464, pladienolide, and herboxidiene were discovered as activators of reporter gene systems. Unexpectedly, these compounds target neither transcription nor translation; rather, they target splicing factor 3B subunit 1 of the spliceosome, causing changes in splicing patterns. All of them showed anticancer activity in a low nanomolar range. Since their discovery, these molecules have been used in a variety of biological applications. PMID- 26812545 TI - Human cytomegalovirus IE1 protein alters the higher-order chromatin structure by targeting the acidic patch of the nucleosome. AB - Human cytomegalovirus (hCMV) immediate early 1 (IE1) protein associates with condensed chromatin of the host cell during mitosis. We have determined the structure of the chromatin-tethering domain (CTD) of IE1 bound to the nucleosome core particle, and discovered that IE1-CTD specifically interacts with the H2A H2B acidic patch and impairs the compaction of higher-order chromatin structure. Our results suggest that IE1 loosens up the folding of host chromatin during hCMV infections. PMID- 26812547 TI - Redox-Neutral Couplings between Amides and Alkynes via Cobalt(III)-Catalyzed C-H Activation. AB - C-H activation assisted by a bifunctional directing group has allowed the construction of heterocycles. This is ideally catalyzed by earth-abundant and eco friendly transition metals. We report Co(III)-catalyzed redox-neutral coupling between arenes and alkynes using an NH amide as an electrophilic directing group. The redox-neutral C-H activation/coupling afforded quinolines with water as the sole byproduct. PMID- 26812548 TI - Blood DNA Yield but Not Integrity or Methylation Is Impacted After Long-Term Storage. AB - Collection of human whole blood for genomic DNA extraction is part of numerous clinical studies. Since DNA extraction cannot always be performed at the time of sample collection, whole blood samples may be stored for years before being processed. The use of appropriate storage conditions is then critical to obtain DNA in sufficient quantity and of adequate quality in order to obtain reliable results from the subsequent molecular biological analyses. In this study, EDTA whole blood samples were collected from 8 healthy volunteers, and different durations (up to 1 year) and temperatures (room temperature, 4 degrees C, -20 degrees C, and -80 degrees C) of storage were compared. The effect of the addition of a DNA preservative agent was also assessed before and after storage. DNA concentrations measured by UV spectrophotometry and spectrofluorometry were used to calculate DNA extraction yields and double-strand DNA ratios. DNA integrity was controlled by agarose gel electrophoresis and long-range polymerase chain reaction. The impact of storage conditions on DNA methylation was also evaluated. Results showed that certain storage conditions have a significant impact on the DNA extraction yield but little or no effect on DNA integrity and methylation. Storage of EDTA blood at -80 degrees C guarantees high-quality DNA with a good yield. Higher DNA extraction yields were obtained with the addition of a DNA preservative agent before thawing EDTA blood stored at -20 degrees C or 80 degrees C. Long-term storage at room temperature in the presence of a DNA preservative agent also appeared to be a reliable procedure. PMID- 26812546 TI - Mutation in ATG5 reduces autophagy and leads to ataxia with developmental delay. AB - Autophagy is required for the homeostasis of cellular material and is proposed to be involved in many aspects of health. Defects in the autophagy pathway have been observed in neurodegenerative disorders; however, no genetically-inherited pathogenic mutations in any of the core autophagy-related (ATG) genes have been reported in human patients to date. We identified a homozygous missense mutation, changing a conserved amino acid, in ATG5 in two siblings with congenital ataxia, mental retardation, and developmental delay. The subjects' cells display a decrease in autophagy flux and defects in conjugation of ATG12 to ATG5. The homologous mutation in yeast demonstrates a 30-50% reduction of induced autophagy. Flies in which Atg5 is substituted with the mutant human ATG5 exhibit severe movement disorder, in contrast to flies expressing the wild-type human protein. Our results demonstrate the critical role of autophagy in preventing neurological diseases and maintaining neuronal health. PMID- 26812549 TI - Geometry of an Isolated Dimer of Imidazole Characterised by Rotational Spectroscopy and Ab Initio Calculations. AB - An isolated, gas-phase dimer of imidazole is generated through laser vaporisation of a solid rod containing a 1:1 mixture of imidazole and copper in the presence of an argon buffer gas undergoing supersonic expansion. The complex is characterised through broadband rotational spectroscopy and is shown to have a twisted, hydrogen-bonded geometry. Calculations at the CCSD(T)(F12*)/cc-pVDZ-F12 level of theory confirm this to be the lowest-energy conformer of the imidazole dimer. The distance between the respective centres of mass of the imidazole monomer subunits is determined to be 5.2751(1) A, and the twist angle gamma describing rotation of one monomer with respect to the other about a line connecting the centres of mass of the monomers is determined to be 87.9(4) degrees . Four out of six intermolecular parameters in the model geometry are precisely determined from the experimental rotational constants and are consistent with results calculated ab initio. PMID- 26812551 TI - From the Editor-in-Chief's Desk. PMID- 26812550 TI - Consensus document on the evaluation and treatment of moderate-to-severe psoriasis: Psoriasis Group of the Spanish Academy of Dermatology and Venereology. AB - Psoriasis is a highly prevalent disease with a major impact on quality of life; therefore, appropriate patient management is mandatory. Given that many issues in psoriasis are controversial and not clearly defined by evidence-based medicine, management of psoriasis is very variable. Expert consensus can generate practical guidelines for optimization of patient care. Much has changed since 2009, when the Consensus Document on the Evaluation and Treatment of Moderate to Severe Psoriasis was published by the Spanish Psoriasis Group (GEP) of the Spanish Academy of Dermatology and Venereology (AEDV). The objective of the present consensus document is to provide the dermatologist with updated recommendations for the evaluation and treatment of patients with moderate-to-severe plaque psoriasis. All active members of the GEP of the AEDV were invited to participate in the survey. The final group comprised 46 members from various areas of Spain and with substantial experience in managing psoriasis. A 3-round Delphi process was used to reach consensus. Consistent agreement and consistent disagreement (consensus) required the achievement of at least two of the following three criteria: Criterion 1, which was based on the position occupied by the mean on a scale of 1-9 and an SD <2; Criterion 2, which was based on the median and interquartile range (IQR) on a scale of 1-9; Criterion 3, which considered the percentage of the voting experts on a scale of 1-9. The items studied were definition of severity, therapeutic objectives, indications for systemic treatment and biologic therapy, induction and maintenance periods, therapeutic failure, loss of response, relapse and rebound, continuous and intermittent therapy, screening of patients before treatment, adherence to therapy, follow-up of treatment outcome, combination of drugs, transitioning and associated comorbidities. Consistent agreement or disagreement (consensus) was achieved for 198 items (agreement, 3 criteria 146 items, 2 criteria 43 items; disagreement, 3 criteria 9 items, 2 criteria 0 items) based on the criteria described above. Completion of the Delphi consensus process enabled a broad and experienced group of Spanish psoriasis experts to provide useful and practical guidelines for the management and treatment of patients with moderate-to-severe psoriasis, particularly in areas where evidence is lacking. PMID- 26812552 TI - Cancer-Related Distress in Young Adults Compared to Middle-Aged and Senior Adults. AB - PURPOSE: Little is known about cancer-related distress during young adulthood. Results from the few studies that have directly assessed this age group have indicated that young adults (YAs) may be at greater risk of developing psychosocial difficulties due to their unique challenges of coping with cancer. This study's objective was to investigate cancer-related distress in YAs compared to older adults. METHODS: This retrospective cross-sectional study compared the distress level of YAs (18-39 years old) with that of middle-aged (40-64 years old) and senior adults (65-90 years old) using the Distress Thermometer (DT) and associated Problem List (PL). Factors that may be associated with distress by age group were examined, including demographics, cancer type, and PL items endorsed. RESULTS: YAs had higher cancer-related distress than senior adults but similar distress levels to middle-aged adults. Findings from distress comparisons across demographics, cancer types, and PL items endorsed suggest that YAs and middle aged adults had similar distress patterns when compared to senior adults, who had the lowest DT scores. Multivariable analyses indicated age-related risk factors for high distress, including gynecologic cancers for YAs; divorced, single, or unemployed statuses for middle-aged adults; and being of Hispanic ethnicity for senior adults. Female gender and practical, emotional, and physical problems were associated with distress for all age groups. CONCLUSION: There is a differential impact of cancer by age. It is important to screen for cancer-related distress, paying attention to risk factors by age to determine age-appropriate supportive care needs. PMID- 26812553 TI - Alleviating Emotional Distress in Adolescent and Young Adult Cancer Survivors: An Open Trial of Metacognitive Therapy. AB - PURPOSE: Metacognitive therapy (MCT) is an effective psychological treatment for a range of emotional disorders. However, the applicability of MCT to treating emotional distress in physical health populations has yet to be tested. The present study examined the potential of MCT for alleviating emotional distress in adolescent and young adult cancer (AYAC) survivors. METHODS: Twelve AYAC survivors, aged 18-23, who had completed acute medical treatment participated in this pilot open trial with 6 months follow-up. Each participant completed a baseline period followed by 8-14 sessions of MCT that targeted perseverative thinking (worry and rumination), attentional control, and metacognitive beliefs. The primary outcome variable was severity of depression and anxiety symptoms as measured by the Hospital Anxiety and Depression Scale (HADS). RESULTS: MCT was associated with large and statistically significant reductions in anxiety, depression, trauma symptoms, and metacognitive beliefs and processes. In the intention-to-treat sample, 50% of participants met standardized criteria for recovery on the HADS at posttreatment and these gains were maintained through to 6-month follow-up. CONCLUSION: MCT is a promising transdiagnostic approach to treating different forms of emotional distress in AYAC survivors. Further investigation in controlled trials is now warranted. PMID- 26812554 TI - Prevalence and Intensity of Pain and Other Physical and Psychological Symptoms in Adolescents and Young Adults Diagnosed with Cancer on Referral to a Palliative Care Service. AB - PURPOSE: While adolescent and young adult (AYA) oncology is recognized as a distinct specialty, there remains a paucity of literature documenting symptomatology in this cohort. This study aimed to identify the prevalence, severity, and mechanism of pain and other symptoms in AYA patients referred to a palliative care service in a specialist Australian cancer center. METHODS: A retrospective design analyzed the case file data of 33 eligible AYA patients aged 15-25 years old at diagnosis and two randomly selected control groups of patients >25 years old: unmatched and matched for diagnosis and sex. All cases were referred to the palliative care service between July 2009 and June 2012. Descriptive statistics, analysis of Edmonton Symptom Assessment Scale (ESAS) and Edmonton Classification System of Cancer Pain (ECS-CP) data, and non-parametric tests were performed. RESULTS: The most common malignancies among the AYA patients were sarcoma and hematological cancers. All AYA patients reported pain syndrome on the ECS-CP compared with 85% of the matched controls (p=0.018). An age group effect was found for mechanisms of pain (p=0.035). A trend toward more neuropathic pain among AYA cases was also found (59% vs. 39%). The most common ESAS symptoms in AYAs were pain (91%), diminished well-being (76%), fatigue (75%), and decreased appetite (67%). CONCLUSION: AYA cancer patients appear to experience a unique symptom profile with high symptom prevalence and complexity. Further research is warranted to identify determinants and inform integration of supportive and palliative care services for this unique patient cohort. PMID- 26812555 TI - Survival Differences by Race/Ethnicity and Neighborhood Socioeconomic Status in Adolescents and Young Adults Diagnosed with Non-Hodgkin Lymphoma. AB - PURPOSE: Lymphoid malignancies are among the most common cancers diagnosed in adolescents and young adults (AYAs). However, little is known about the factors affecting survival in AYAs with non-Hodgkin lymphoma (NHL). We evaluated if survival differs by race/ethnicity and neighborhood socioeconomic status in AYAs with NHL. METHODS: AYAs aged 15-39 diagnosed with incident NHL during 1990-2010 at Kaiser Permanente Southern California (KPSC), a large managed care organization, were identified. Demographic information and cancer characteristics were obtained from KPSC's cancer registry. Mortality data were obtained from California and national death files. Patients were followed from NHL diagnosis to 5 years postdiagnosis or 12/31/2012, whichever came first. Multivariable Cox model was used to evaluate the association between race/ethnicity, neighborhood income/education level, and mortality, adjusting for age, gender, stage, year of diagnosis, and histology subtype. RESULTS: A total of 718 AYAs with NHL were included (mean age at diagnosis: 31 years); 45% were non-Hispanic white, 10% were African American, 36% were Hispanic, and 8% were Asian/Pacific Islander. Overall 5-year mortality was 30%. Compared to non-Hispanic whites, Asians/Pacific Islanders had increased 5-year mortality (hazard ratio=1.95, 95% confidence interval: 0.93-4.07). No significant increase in mortality was found for Hispanics or African Americans. Lower neighborhood income but not education level was associated with worse overall survival. CONCLUSION: A survival disparity for Asians/Pacific Islanders and low-income neighborhoods was observed in AYAs with NHL despite relatively equal access to care. These results call for studies to further understand mechanisms underlying the inferior outcomes among disadvantaged subgroups. PMID- 26812557 TI - Letter to the Editor: Management of Concurrent Pregnancy and Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma. Comment on the Article by Zaidi et al. PMID- 26812558 TI - Response to the Letter to the Editor from Bleyer. PMID- 26812556 TI - A Qualitative Study of the Impact of Cancer on Romantic Relationships, Sexual Relationships, and Fertility: Perspectives of Canadian Adolescents and Parents During and After Treatment. AB - PURPOSE: We sought to gain insight into perspectives around core domains of adolescent development--romantic relationships, sexual relationships, and fertility--from the vantage point of Canadian adolescents and parents during and after cancer treatment. METHODS: Twenty adolescents (12-17 years old at interview) and 20 parents (who may or may not have had an adolescent interviewed) participated in this study. Using a semistructured guide, adolescents and parents were interviewed separately. All interviews were audio-recorded and transcribed. Transcribed interview data were independently coded according to the study objectives by two trained analysts. Codes were organized into categories that reflected emerging themes. Discrepancies in coding were resolved through discussion with the lead investigator. RESULTS: Qualitative analysis revealed main themes for adolescents and parents related to: (1) romantic relationships (opinions on the importance of dating in the context of cancer, expectations that cancer will impact future relationships, dating as a source of moral support, and limited opportunities to engage with partners); (2) sexual relationships (thoughts related to the impact of cancer on future sexual relationships); (3) fertility (initiating treatment as a primary concern and fear of infertility and perceived consequences); and (4) recommendations for care (access to knowledge and support through adolescent-friendly and accessible means). CONCLUSION: Findings from this study highlight cancer-specific relationship and fertility issues faced by adolescents and provide important direction to the development of interventions that may ultimately improve the psychosocial health of adolescents during and after cancer treatment. PMID- 26812559 TI - Features of childhood Sjogren's syndrome in comparison to adult Sjogren's syndrome: considerations in establishing child-specific diagnostic criteria. AB - OBJECTIVES: To describe the clinical features of childhood Sjogren's syndrome (SS) in comparison to adult SS and to evaluate possible child-specific modifications to existing adult criteria for use in diagnosing childhood SS. METHODS: We retrospectively identified children (age <18 years) with SS and compared the clinical, laboratory, and histopathological features of these children based on presence or absence of parotitis. We compared these features to adults with SS and evaluated the applicability of existing classification criteria in diagnosing childhood SS. Child-specific modifications to existing criteria were evaluated. RESULTS: Twenty-six children were included in our childhood SS group. Sixteen children had parotitis at or before presentation. Absence of parotitis was associated with greater degree of organ damage based on SS disease damage index. Compared to 413 adult SS patients, childhood SS was more commonly associated with parotitis, positive serologies, neurologic and nephrologic manifestations, and non-specific features (fever, lymphadenopathy) but less commonly associated with dry mouth and dry eyes. Only a minority of these children met previously established criteria for adult SS. Inclusion of child-specific features such as parotitis and the presence of any focal lymphocytic sialadenitis on minor salivary gland biopsy increased the proportion of children meeting these criteria. CONCLUSIONS: Childhood SS features may be different than adult SS features necessitating child-specific criteria for better diagnosis of childhood SS, a key step towards better understanding the features, prognosis, and outcomes in this disease. PMID- 26812560 TI - Photoassociation Spectroscopy in Penning Ionization Reactions at Sub-Kelvin Temperatures. AB - Penning ionization reactions in merged beams with precisely controlled collision energies have been shown to accurately probe quantum mechanical effects in reactive collisions. A complete microscopic understanding of the reaction is, however, faced with two major challenges-the highly excited character of the reaction's entrance channel and the limited precision of even the best state-of the-art ab initio potential energy surfaces. Here, we suggest photoassociation spectroscopy as a tool to identify the character of orbiting resonances in the entrance channel and probe the ionization width as a function of interparticle separation. We introduce the basic concept, using the example of metastable helium and argon, and discuss the general conditions under which this type of spectroscopy will be successful. PMID- 26812561 TI - A New Journal to Improve Care for Adolescent and Young Adult Oncology Patients and Survivors. PMID- 26812562 TI - What Should the Age Range Be for AYA Oncology? PMID- 26812563 TI - Palliative Care for Adolescents and Young Adults: A Pediatric Perspective. PMID- 26812564 TI - Trailblazers in Adolescent and Young Adult Oncology. PMID- 26812565 TI - Treatment of Acute Lymphoblastic Leukemia in Adolescents and Young Adults. AB - Treatment outcomes have significantly improved for children with acute lymphoblastic leukemia (ALL), a relatively common childhood cancer, with 5-year survival rates over 80%. However, survival rates for adolescents and young adults (AYAs) with ALL are lower than that for their younger counterparts. Despite marked heterogeneity in the biology of ALL, advancing age appears to be associated with an increased incidence of prognostically unfavorable cytogenetic abnormalities and a decreased incidence of favorable cytogenetic abnormalities. Retrospective analyses indicate that AYAs display superior remission and survival rates when treated with a pediatric rather than an adult protocol. This is thought to, in part, reflect differences in drug selection and dose intensity, with typical pediatric treatment regimens incorporating higher total doses of vincristine, l-asparaginase, and glucocorticoids than adult regimens, which tend to use more myelosuppressive agents. The tolerability and efficacy of intensive pediatric regimens are being tested prospectively in the AYA population. This review will describe the biology, treatment approaches, and therapy-related toxicities for AYAs with ALL. PMID- 26812566 TI - Evaluation and Preservation of Fertility in Patients with Testicular Cancer. AB - Young men presenting with testicular cancer enjoy a very high prospect of cure and look forward to an average of 40 additional years of life. As such, emphasis has focused on care algorithms that are not only curative, but also minimize the consequences of the disease and associated treatments on subsequent quality of life. Concerns regarding therapy-related second malignancies and cardiovascular disease have led to management strategies emphasizing the reduction or elimination of chemotherapy and radiation therapy and increase utilization of surveillance for early-stage patients. Germ cell tumors present typically in the late 20s or early 30s, occurring in a timeframe when many young men begin to consider their families seriously. Indeed, more than 80% of young patients report significant concerns regarding diminished fertility. The biology and anatomy of most germ cell tumors lead to significant potential for disrupted fertility from both disease-related factors-hypogonadism and diminished native spermatogenesis and manifold treatment-related complications such as ejaculatory dysfunction, chemotherapy, and radiation effects on spermatogenesis and testosterone production. Despite these unique challenges of managing fertility in patients with germ cell tumors, such efforts are rewarded with a high rate of fertility preservation for most patients with no evidence that subsequent progeny are affected by the parent's disease or treatments. Herein, we review the biological and clinical issues associated with reduced fertility potential in patients with germ cell tumors, methods for evaluating and preserving fertility in such patients, and anticipated overall success rates. PMID- 26812567 TI - Latest Estimates of Survival Rates of the 24 Most Common Cancers in Adolescent and Young Adult Americans. AB - PURPOSE: A need to examine survival trends of individual cancers in older adolescents and young adults (AYAs) is prompted by overall survival trends that have indicated a lack of progress in survival improvement for AYAs compared with both younger and older cancer patients. PATIENTS AND METHODS: The most recent Surveillance, Epidemiology and End Results (SEER) data were used to ascertain survival trends of the 24 most frequent cancers in AYAs. RESULTS: Of the 20 types of cancers in 15- to 39-year-olds evaluable for survival rate trends, only eight had evidence for a statistically significant improvement in their age-adjusted 5 year survival rate since 1985. As of 2000-2007, of the 24 most common types of cancer in American AYAs, nine had an age-adjusted 5-year survival rate in excess of 80% and eight had a survival rate below 60%. In 19 of 21 cancers for which a comparison of survival by gender is feasible, AYA males had a worse survival rate than females. Of the 23 types of cancer that are classifiable as distant disease, 13 had 5-year survival rates of less than 30%. CONCLUSION: While some progress has been made, the lack of improvement for some cancers with distant disease is disappointing. Increased survival of AYA cancer patients offers significant societal gains in terms of years of productivity compared to older adults. If the potential long-term economic impact of health in AYAs is considered, the need to improve the survival of AYAs with cancer is obvious. PMID- 26812568 TI - The History and Accomplishments of the LIVESTRONG Young Adult Alliance. AB - PURPOSE: This article outlines the history, background, and accomplishments of the LIVESTRONG Young Adult Alliance. BACKGROUND: The LIVESTRONG Young Adult Alliance, a program of the Lance Armstrong Foundation, was developed as a vehicle for a strategic plan designed to implement the Adolescent and Young Adult Oncology Progress Review Group (AYAO PRG) recommendations. The AYAO PRG was co sponsored by Lance Armstrong Foundation and the National Cancer Institute (NCI); both LIVESTRONG and NCI provide strategic oversight and guidance to the Alliance. Highlights and accomplishments: The Alliance accomplishments include the publication of disease-specific retrospective analyses, funding of an AYA cohort study and biorepository proposal, publication of two position statements on guidelines for care of AYAs with cancer and training for AYA oncology health professionals, promotion of an international charter of rights for AYA cancer patients, creation and distribution of a survey to college health professionals, creation and implementation of a Cancer Centers Working Group and Institutional Review Board Toolkit, and continued growth and collaboration through an annual meeting. CONCLUSION: The growth and success of the Alliance has coincided with the growth of AYA oncology as a field. The collaborative environment of the Alliance draws together a diverse group of individuals united in the effort to increase survival rates and improve the quality of life for adolescents and young adults diagnosed with cancer. PMID- 26812569 TI - The International Charter of Rights for Young People with Cancer. AB - The International Charter of Rights for Young People with Cancer is a global internet-based initiative set up by five charities from across the world. They are calling on the international community to recognize that access to quality cancer care is a right, not a privilege, and to improve the services and support that young people diagnosed with cancer receive, regardless of geographical location. PMID- 26812571 TI - Voices of AYAO. PMID- 26812570 TI - Expanded Access Through Cancer Trials Support Unit to Children's Oncology Group Sarcoma Trial AEWS1031 for Adolescents and Young Adults. PMID- 26812574 TI - Rehabilitation of Executive Functions in Patients with Chronic Acquired Brain Injury with Goal Management Training, External Cuing, and Emotional Regulation: A Randomized Controlled Trial. AB - Executive dysfunction is a common consequence of acquired brain injury (ABI), causing significant disability in daily life. This randomized controlled trial investigated the efficacy of Goal Management Training (GMT) in improving executive functioning in patients with chronic ABI. Seventy patients with a verified ABI and executive dysfunction were randomly allocated to GMT (n=33) or a psycho-educative active control condition, Brain Health Workshop (BHW) (n=37). In addition, all participants received external cueing by text messages. Neuropsychological tests and self-reported questionnaires of executive functioning were administered pre-intervention, immediately after intervention, and at 6 months follow-up. Assessors were blinded to group allocation. Questionnaire measures indicated significant improvement of everyday executive functioning in the GMT group, with effects lasting at least 6 months post treatment. Both groups improved on the majority of the applied neuropsychological tests. However, improved performance on tests demanding executive attention was most prominent in the GMT group. The results indicate that GMT combined with external cueing is an effective metacognitive strategy training method, ameliorating executive dysfunction in daily life for patients with chronic ABI. The strongest effects were seen on self-report measures of executive functions 6 months post-treatment, suggesting that strategies learned in GMT were applied and consolidated in everyday life after the end of training. Furthermore, these findings show that executive dysfunction can be improved years after the ABI. PMID- 26812572 TI - A urinary microRNA signature can predict the presence of bladder urothelial carcinoma in patients undergoing surveillance. AB - BACKGROUND: The objective of this study was to determine whether microRNA (miRNA) profiling of urine could identify the presence of urothelial carcinoma of the bladder (UCB) and to compare its performance characteristics to that of cystoscopy. METHODS: In the discovery cohort we screened 81 patients, which included 21 benign controls, 30 non-recurrers and 30 patients with active cancer (recurrers), using a panel of 12 miRNAs. Data analysis was performed using a machine learning approach of a Support Vector Machine classifier with a Student's t-test feature selection procedure. This was trained using a three-fold cross validation approach and performance was measured using the area under the receiver operator characteristic curve (AUC). The miRNA signature was validated in an independent cohort of a further 50 patients. RESULTS: The best predictor to distinguish patients with UCB from non-recurrers was achieved using a combination of six miRNAs (AUC=0.85). This validated in an independent cohort (AUC=0.74) and detected UCB with a high sensitivity (88%) and sufficient specificity (48%) with all significant cancers identified. The performance of the classifier was best in detecting clinically significant disease such as presence of T1 Stage disease (AUC=0.92) and high-volume disease (AUC=0.81). Cystoscopy rates in the validation cohort would have been reduced by 30%. CONCLUSIONS: Urinary profiling using this panel of miRNAs shows promise for detection of tumour recurrence in the surveillance of UCB. Such a panel may be useful in reducing the morbidity and costs associated with cystoscopic surveillance, and now merits prospective evaluation. PMID- 26812573 TI - New ARCHITECT plasma pro-gastrin-releasing peptide assay for diagnosing and monitoring small-cell lung cancer. AB - BACKGROUND: Progastrin-releasing peptide (ProGRP) is a potential marker for small cell lung cancer (SCLC) in serum; however, it may be more stable in plasma. We investigated a new plasma assay (ProGRPp) and its usefulness in diagnosing and monitoring SCLC. METHODS: The marker concentrations were determined on the ARCHITECT i system. RESULTS: The assay could distinguish SCLC from non-small-cell lung cancer (NSCLC: area under the curve 0.931, 95% CI 0.893-0.969; cross validated accuracy 0.813; sensitivity 84.0%, specificity 96.3%; at 140 pg ml(-1) cutoff). The probability of SCLC when ProGRPp was >140 pg ml(-1) was 91.8%, after adjusting for age, gender, and renal dysfunction. The NSCLC patients with ProGRPp >140 pg ml(-1) were at high risk (odds ratio=37.0, P<0.001) for tumours with neuroendocrine features. False negatives in SCLC were associated with a lack of thyroid transcription factor-1 (P<0.001). A decrease of ProGRPp to <140 pg ml(-1) during chemotherapy was significantly associated with the image-based response (P<0.001), and independently affected progression-free survival (PFS, relative risk=2.51, P=0.04) and overall survival (OS, relative risk=4.38, P=0.003), after adjustment for imaging response, performance status, and stage. CONCLUSIONS: The ProGRPp assay is specific and sensitive for diagnosing SCLC. Changes in ProGRPp during chemotherapy are significantly associated with image-based response, PFS, and OS. PMID- 26812575 TI - A sterilization system using ultraviolet photochemical reactions based on nitrous oxide and oxygen gases. AB - Active oxygen species (AOS) generated under ultraviolet (UV) lamps can be applied for various industrial processes owing to extremely strong oxidative abilities. We have already reported on an application of the AOS for a sterilization process of microorganisms. Here, a sterilization method using active oxygen generated under ultraviolet (UV) lamps introducing nitrous oxide (N2O) and oxygen gases into a vacuum chamber was investigated. Nitrogen dioxide (NO2) gas was readily produced from N2O by UV photochemical reactions under the low-pressure mercury lamp and then used to sterilize medical devices. We compared the ability of the N2O gas to sterilize Geobacillus stearothermophilus spores with those of conventional methods. Successful sterilization of spores on various biological indicators was achieved within 60 min, not only in sterilization bags but also in a lumen device. PMID- 26812576 TI - Studying long 16S rDNA sequences with ultrafast-metagenomic sequence classification using exact alignments (Kraken). AB - Ultrafast-metagenomic sequence classification using exact alignments (Kraken) is a novel approach to classify 16S rDNA sequences. The classifier is based on mapping short sequences to the lowest ancestor and performing alignments to form subtrees with specific weights in each taxon node. This study aimed to evaluate the classification performance of Kraken with long 16S rDNA random environmental sequences produced by cloning and then Sanger sequenced. A total of 480 clones were isolated and expanded, and 264 of these clones formed contigs (1352 +/- 153 bp). The same sequences were analyzed using the Ribosomal Database Project (RDP) classifier. Deeper classification performance was achieved by Kraken than by the RDP: 73% of the contigs were classified up to the species or variety levels, whereas 67% of these contigs were classified no further than the genus level by the RDP. The results also demonstrated that unassembled sequences analyzed by Kraken provide similar or inclusively deeper information. Moreover, sequences that did not form contigs, which are usually discarded by other programs, provided meaningful information when analyzed by Kraken. Finally, it appears that the assembly step for Sanger sequences can be eliminated when using Kraken. Kraken cumulates the information of both sequence senses, providing additional elements for the classification. In conclusion, the results demonstrate that Kraken is an excellent choice for use in the taxonomic assignment of sequences obtained by Sanger sequencing or based on third generation sequencing, of which the main goal is to generate larger sequences. PMID- 26812577 TI - The yield and quality of cellular and bacterial DNA extracts from human oral rinse samples are variably affected by the cell lysis methodology. AB - Recent culture-independent studies have enabled detailed mapping of human microbiome that has not been hitherto achievable by culture-based methods. DNA extraction is a key element of bacterial culture-independent studies that critically impacts on the outcome of the detected microbial profile. Despite the variations in DNA extraction methods described in the literature, no standardized technique is available for the purpose of microbiome profiling. Hence, standardization of DNA extraction methods is urgently needed to yield comparable data from different studies. We examined the effect of eight different cell lysis protocols on the yield and quality of the extracted DNA from oral rinse samples. These samples were exposed to cell lysis techniques based on enzymatic, mechanical, and a combination of enzymatic-mechanical methods. The outcome measures evaluated were total bacterial population, Firmicutes levels and human DNA contamination (in terms of surrogate GAPDH levels). We noted that all three parameters were significantly affected by the method of cell lysis employed. Although the highest yield of gDNA was obtained using lysozyme-achromopeptidase method, the lysozyme-zirconium beads method yielded the peak quantity of total bacterial DNA and Firmicutes with a lower degree of GAPDH contamination compared with the other methods. Taken together our data clearly points to an urgent need for a consensus, standardized DNA extraction technique to evaluate the oral microbiome using oral rinse samples. Further, if Firmicutes levels are the focus of investigation in oral rinse microbiome analyses then the lysozyme-zirconium bead method would be the method of choice in preference to others. PMID- 26812578 TI - Phage Selection of Peptide Macrocycles against beta-Catenin To Interfere with Wnt Signaling. AB - Upregulation of beta-catenin, the primary mediator of the Wnt signaling pathway, plays an important role in the tumorigenesis of several types of human cancer. Targeting beta-catenin to interfere with its ability to serve as a translational co-activator is considered an attractive therapeutic approach. However, the development of inhibitors has been challenging because of the lack of obvious binding pockets for ligands, and because inhibitors should not interfere with other beta-catenin functions. Only two ligands with known molecular interactions with beta-catenin have been developed so far, and are based on stabilized alpha helical peptides. In this study, we screened a large combinatorial library of bicyclic peptides by phage display. Binders to different surface regions of beta catenin were identified. The binding site of one group of ligands was mapped to the interaction region of the translational Wnt inhibitor ICAT (inhibitor of beta catenin and Tcf), which is a prime target site on beta-catenin for therapeutic intervention, and to which no ligands could be developed before. PMID- 26812580 TI - Unraveling The Origin of Enhanced Field Emission from Irradiated FeCo-SiO2 Nanocomposites: A Combined Experimental and First-Principles Based Study. AB - This work is driven by the vision of engineering planar field emitters with ferromagnetic metal-insulator nanocomposite thin films, using swift heavy ion (SHI) irradiation method. FeCo nanoparticles inside SiO2 matrix, when subjected to SHI get elongated. Using this, we demonstrate here a planar field emitter with maximum current density of 550 MUA/cm(2) at an applied field of 15 V/MUm. The film, irradiated with 5 * 10(13) ions/cm(2) fluence (5e13) of 120 MeV Au(9+) ions, shows very high electron emitting quantum efficiency in comparison to its unirradiated counterpart. Surface enhanced Raman spectroscopy analysis of unirradiated and 5e13 films further confirms that the field emission (FE) enhancement is not only due to surface protrusions but also depends on the properties of entire matrix. We find experimental evidence of enhanced valence band density of states (VB DOS) for 5e13 film from XPS, which is verified in the electronic structure of a model FeCo cluster from first-principles based calculations combining density functional theory (DFT) and molecular dynamics (MD) simulations. The MD temperature is selected from the lattice temperature profile inside nanoparticles as deduced from thermal spike model. Increasing the irradiation fluence beyond 5e13, results in reduced VB DOS and melting of surface protrusions, thus causing reduction of FE current density. We finally conclude from theoretical analysis that change in fluence alters the co-ordination chemistry followed by the charge distribution and spin alignment, which influence the VB DOS and concurrent FE as evident from our experiment. PMID- 26812581 TI - A fluorescent switchable AIE probe for selective imaging of dipeptidyl peptidase 4 in vitro and in vivo and its application in screening DPP-4 inhibitors. AB - A novel fluorescent probe for in vitro and in vivo imaging of dipeptidyl peptidase-4 (DPP-4) was designed and synthesized. This probe is successfully utilized to screen DPP-4 inhibitors in living 3T3-L1 cells and zebrafish, which provides a novel approach for the discovery of anti-diabetes drugs. PMID- 26812579 TI - Prognostic Indicators for Ebola Patient Survival. AB - To determine whether 2 readily available indicators predicted survival among patients with Ebola virus disease in Sierra Leone, we evaluated information for 216 of the 227 patients in Bo District during a 4-month period. The indicators were time from symptom onset to healthcare facility admission and quantitative real-time reverse transcription PCR cycle threshold (Ct), a surrogate for viral load, in first Ebola virus-positive blood sample tested. Of these patients, 151 were alive when detected and had reported healthcare facility admission dates and Ct values available. Time from symptom onset to healthcare facility admission was not associated with survival, but viral load in the first Ebola virus-positive blood sample was inversely associated with survival: 52 (87%) of 60 patients with a Ct of >24 survived and 20 (22%) of 91 with a Ct of <24 survived. Ct values may be useful for clinicians making treatment decisions or managing patient or family expectations. PMID- 26812582 TI - Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs. AB - The advent of induced pluripotent stem cells (iPSCs) revolutionized human genetics by allowing us to generate pluripotent cells from easily accessible somatic tissues. This technology can have immense implications for regenerative medicine, but iPSCs also represent a paradigm shift in the study of complex human phenotypes, including gene regulation and disease. Yet, an unresolved caveat of the iPSC model system is the extent to which reprogrammed iPSCs retain residual phenotypes from their precursor somatic cells. To directly address this issue, we used an effective study design to compare regulatory phenotypes between iPSCs derived from two types of commonly used somatic precursor cells. We find a remarkably small number of differences in DNA methylation and gene expression levels between iPSCs derived from different somatic precursors. Instead, we demonstrate genetic variation is associated with the majority of identifiable variation in DNA methylation and gene expression levels. We show that the cell type of origin only minimally affects gene expression levels and DNA methylation in iPSCs, and that genetic variation is the main driver of regulatory differences between iPSCs of different donors. Our findings suggest that studies using iPSCs should focus on additional individuals rather than clones from the same individual. PMID- 26812584 TI - Effect of Geometrical Distortion on the Electronic Structure: Synthesis and Characterization of Monoradical-Coordinated Mononuclear Cu(II) Complexes. AB - Ligand H3Sami(Mixed(tBu)) was composed of two different compartments, a redox active 2-aminophenol and a salen salicylidene. Both compartments were linked via a benzyl linker. The ligand reacted with CuCl2.2H2O under air in the presence of Et3N and provided the corresponding monoradical-coordinated mononuclear Cu(II) complex (1). Complex 1, in solution, reacted with air and provided complex 2 via ligand-centered oxygenation at the benzyl-CH2 position. Both complexes were characterized via IR, mass spectrometry, X-ray single-crystal diffraction, variable-temperature magnetic susceptibility, cyclic voltammograms (CVs), and UV vis/NIR spectroscopic techniques. X-ray crystallographic analyses clearly showed almost equally distorted square planar geometry around the Cu(II) atom in both complexes. However, the bending of the radical-containing C6 ring compared to the N1-Cu1-O1 plane was different in both complexes. While complex 1 was paramagnetic and showed a ferromagnetic coupling between the d(x(2)-y(2)) magnetic orbital of Cu(II) ion and the p(z) orbital of coordinated pi-radical, complex 2 was diamagnetic by experiencing a strong antiferromagnetic coupling between the two magnetic orbitals. UV-vis/NIR spectra of the complexes were dominated by charge transfer transitions. CVs of the complexes showed two reversible one-electron oxidations and one reversible one-electron reduction. E(1/2)(ox2) and E(1/2)(red1) potentials were different in both complexes, while E(1/2)(ox1) values were almost the same and the process corresponded to the formation of phenoxyl radical. Theoretical studies were also performed to understand the magnetic coupling phenomena, and TD-DFT calculations were employed for the assignment of charge-transfer absorption bands. PMID- 26812585 TI - Aberrant Ascaris suum Nematode Infection in Cattle, Missouri, USA. PMID- 26812583 TI - Nanopore Sequencing as a Rapidly Deployable Ebola Outbreak Tool. AB - Rapid sequencing of RNA/DNA from pathogen samples obtained during disease outbreaks provides critical scientific and public health information. However, challenges exist for exporting samples to laboratories or establishing conventional sequencers in remote outbreak regions. We successfully used a novel, pocket-sized nanopore sequencer at a field diagnostic laboratory in Liberia during the current Ebola virus outbreak. PMID- 26812586 TI - Fungal biotransformation of chlorogenic and caffeic acids by Fusarium graminearum: New insights in the contribution of phenolic acids to resistance to deoxynivalenol accumulation in cereals. AB - Fusarium Head Blight and Gibberella Ear Rot, mainly caused by the fungi Fusarium graminearum and Fusarium culmorum, are two of the most devastating diseases of small-grain cereals and maize. In addition to yield loss, these diseases frequently result in contamination of kernels with toxic type B trichothecenes. The potential involvement of chlorogenic acid in cereal resistance to Fusarium Head Blight and Gibberella Ear Rot and to trichothecene accumulation was the focus of this study. The effects of chlorogenic acid and one of its hydrolyzed products, caffeic acid, on fungal growth and type B trichothecenes biosynthesis were studied using concentrations close to physiological amounts quantified in kernels and a set of F. graminearum and F. culmorum strains. Both chlorogenic and caffeic acids negatively impact fungal growth and mycotoxin production, with caffeic acid being significantly more toxic. Inhibitory efficiencies of both phenolic acids were strain-dependent. To further investigate the antifungal and anti "mycotoxin" effect of chlorogenic and caffeic acids, the metabolic fate of these two phenolic acids was characterized in supplemented F. graminearum broths. For the first time, our results demonstrated the ability of F. graminearum to degrade chlorogenic acid into caffeic, hydroxychlorogenic and protocatechuic acids and caffeic acid into protocatechuic and hydroxycaffeic acids. Some of these metabolic products can contribute to the inhibitory efficiency of chlorogenic acid that, therefore, can be compared as a "pro-drug". As a whole, our data corroborate the contribution of chlorogenic acid to the chemical defense that cereals employ to counteract F. graminearum and its production of mycotoxins. PMID- 26812587 TI - Synthesis of Titania@Carbon Nanocomposite from Urea-Impregnated Cellulose for Efficient Lithium and Sodium Batteries. AB - Nanostructured TiO2 and TiO2@C nanocomposites were prepared directly from urea impregnated cellulose by a simple reaction/diffusion process and evaluated as negative electrode materials for Li and Na batteries. By direct treatment with TiCl4 under anhydrous conditions, the urea impregnation of cellulose impacts both the TiO2 morphology and the carbon left by cellulose after pyrolysis. Hierarchical TiO2 structures with a flower-like morphology grown from-and-at the surface of the cellulose fibers are obtained without any directing agent. The resulting TiO2/cellulose composite is then transformed either into pure TiO2 flowers by calcination in air at 600 degrees C, or into TiO2@C nanocomposites by pyrolysis under Ar at 600 degrees C. Electrochemical studies demonstrate that both samples can (de)insert lithium and sodium ions and are promising electrode materials. PMID- 26812589 TI - Association of kidney stones with atherosclerotic cardiovascular disease among adults in the United States: Considerations by race-ethnicity. AB - BACKGROUND: There is a paucity of research examining the relationship between kidney stones and risk of cardiovascular disease while considering individuals of different race-ethnicities. PURPOSE: The purpose of this study was to examine the association between history of kidney stones and increased odds of atherosclerotic cardiovascular disease (via the Pooled Cohort Equations) across race-ethnicity groups. METHODS: 5571 participants aged 40-79 from the 2007-2012 cycles of the NHANES were used for this study. A history of kidney stones was collected from survey data. Predicted odds of having a 10-year atherosclerotic cardiovascular disease (ASCVD) event was assessed from the Pooled Cohort Equations. RESULTS: After adjustments, having kidney stones was not associated with an increase odds of having an ASCVD event within the next 10-years (OR 1.03; 95% CI: 0.58-1.82, P=0.91). However, among non-Hispanic blacks, those with kidney stones had a 2.24 increased odds (OR 2.24; 95% CI: 1.08-4.66; P=0.03) of having an ASCVD event within the next 10-years when compared to non-Hispanic blacks with no history of a kidney stone. CONCLUSION: Kidney stones were associated with 10 year risk of a future ASCVD event among non-Hispanic blacks. PMID- 26812588 TI - Dispersion of Hydrophobic Co Supracrystal in Aqueous Solution. AB - Assembly of nanoparticles into supracrystals provides a class of materials with interesting optical and magnetic properties. However, supracrystals are mostly obtained from hydrophobic particles and therefore cannot be manipulated in aqueous systems, limiting their range of applications. Here, we show that hydrophobic-shaped supracrystals self-assembled from 8.2 nm cobalt nanoparticles can be dispersed in water by coating the supracrystals with lipid vesicles. A careful characterization of these composite objects provides insights into their structure at different length scales. This composite, suspended in water, retains the crystalline structure and paramagnetic properties of the starting material, which can be moved with an applied magnetic field. PMID- 26812590 TI - Androgen receptors in Purkinje neurons are modulated by systemic testosterone and sexual training in a region-specific manner in the male rat. AB - The androgen receptor (AR) is a widely distributed molecule indicating the spread actions of its ligand steroid, and plays an important role underlying male sexual behavior. Nevertheless, the influence of steroid hormones and their receptors on cerebellar neurons, as foundation of sexual behavior, is largely unknown. We sought to determine the influence of peripheral hormones on the AR expression in Purkinje neurons across cerebellar lobules in the vermis of male rats. First, we found a basal AR expression in Purkinje neurons that was higher in the superficial region than the deep region only in cerebellar lobules 2, 4, 5, 7, 8 and 9. Moreover, only the cerebellar lobule 10 showed a significant difference between the coordinates 0.1, 0.3 and 0.9. Second, males with four sessions of sexual training showed a decreased AR density in cerebellar lobules 7, 8, 9 and 10, but not in lobules 2, 4 or 5 when compared to males with one session of sexual training. However, sexual training did not affect AR expression in Purkinje neurons according to their location in any of the cerebellar lobules studied. Third, castration decreased the AR density in the cerebellar lobules 1, 2, 5 and 9 in the superficial region, while in the deep region all cerebellar lobules, except lobule 6, showed a lower AR density after castration. Finally, testosterone replacement restored AR density to control levels in all cerebellar lobules in the superficial region that were affected by castration. Contrary, in the deep region hormonal replacement failed to restore the AR density to control level in the majority of the cerebellar lobules that were affected by castration. Altogether, our findings indicate that Purkinje neurons in the vermis are influenced by systemic testosterone in a region-dependent manner highlighting a link between the cerebellum and gonads in the male rat. The AR function in Purkinje neurons may be related to cerebellar plasticity since both estrogen and progesterone receptors, members of the nuclear receptor family, regulate plasticity processes in Purkinje neurons. We concluded the cerebellum is an important component of the neural circuit for male sexual behavior. PMID- 26812591 TI - Behavioral and hormonal responses to stress in binge-like eating prone female rats. AB - Binge eating episodes are frequently stimulated by stress. We developed a model of binge eating proneness based on individual sensitivity of young female Sprague Dawley rats to significantly increase sucrose consumption in response to stress. The rats were subjected to unpredictable intermittent 1-h access to 10% sucrose. After the stabilization of sucrose intake, rats were assessed for consistency of higher (for binge-like eating prone, BEP) or lower (for binge-like eating resistant, BER) sucrose intake in response to unpredictable episodes of foot shock stress. The objectives of this study included demonstrating face validity of the BEP model and determining if some of the features of this model were pre existing before exposure to intermittent access to sucrose and repeated stress. The BEP rats consumed a larger (20%>BER) amount of sucrose in a discrete (1-h) period of time compared to the BER phenotype in non-stressful conditions and significantly increased sucrose intake (50%>BER) under stress. Conversely, stress did not affect sucrose intake in BER rats. BEP rats showed higher sucrose intake compared to BER rats at the beginning of darkness as well as during the light period when they were sated and not physically hungry. Analyses of the sucrose licking microstructure revealed that BEP rats had a high motivational drive to consume sucrose in non-stressful condition and an increased hedonic value of sucrose when they were exposed to stressful conditions. BEP rats consumed sucrose much more rapidly under stressful conditions compared to BER rats. Finally, BEP rats demonstrated compulsive-like intake of sucrose (assessed in the light-dark box) and a blunted stress-induced increase in plasma corticosterone levels. Body weight and chow intake were not different between the phenotypes. Before exposure to intermittent access to sucrose and repeated stress, the BEP rats showed no clear evidence for compulsive sucrose intake. However, from the first 1-h access to sucrose, the BEP rats exhibited sucrose overeating; and from the first exposure to stress before intermittent access to sucrose, the BEP rats showed a blunted increase in corticosterone plasma levels. Innate sucrose hyperconsumption and altered reactivity of the hypothalamo-pituitary adrenal (HPA) axis to stress may be involved in the development of binge-like eating. Increased perceived hedonic value of palatable food and an increased motivation to consume this food despite aversive conditions as well as deregulated reactivity of the HPA axis may contribute to stress-induced bingeing on sucrose in BEP rats. PMID- 26812592 TI - Exercise deprivation increases negative mood in exercise-addicted subjects and modifies their biochemical markers. AB - The aim of this study was to identify the possible association between biochemical markers of exercise addiction and affective parameters in a sample of athletes during 2weeks of withdrawal exercise. Eighteen male runners were distributed into a control group (n=10) composed of runners without exercise addiction symptoms and an exercise addiction group (n=8) composed of runners with exercise addiction symptoms. The volunteers performed a baseline evaluation that included affective questionnaires, blood samples, body composition and an aerobic test performed at ventilatory threshold I. After the baseline evaluation, the groups started an exercise withdrawal period that was sustained for 2weeks. During exercise withdrawal, an actigraph accelerometer was used to monitor the movement index, and CK and LDH were measured in blood samples to validate the non exercise practice. At the end of the exercise withdrawal period, a blood collection, aerobic test and mood scale was performed in the re-test. The results showed that at the end of the experimental protocol, when compared with the control group, the exercise addiction group showed an increase in depression, confusion, anger, fatigue and decreased vigor mood that improved post-exercise, along with low levels of anandamide at all time-points evaluated and a modest increase in beta-endorphin post-exercise. Moreover, the exercise addiction group showed a decrease in oxygen consumption and respiratory exchange ratio after the exercise withdrawal period, which characterized a detraining phenomenon. Our data suggest that a 2-week withdrawal exercise period resulted in an increase of negative mood in exercise addiction; additionally, exercise addiction showed low levels of anandamide. PMID- 26812593 TI - Parents of terror victims. A longitudinal study of parental mental health following the 2011 terrorist attack on Utoya Island. AB - BACKGROUND AND AIMS: Little is known about parents' health following their children's exposure to trauma. We investigated the mental health of parents of young terrorist survivors and assessed parental distress and guilt as potential predictors of mental health. METHOD: Mothers and fathers (N=531) participated in two study waves 4-5 and 14-15 months after the shooting. Posttraumatic stress reactions (PTSS) and anxiety/depression were compared with age- and gender adjusted expected scores that were calculated from a concurrent population study. Mixed effects models investigated the associations between parental distress, parental guilt, and mental health. RESULTS: Parents' level of anxiety/depression was three times higher and PTSS was five times higher than that of the general population. Parental distress and guilt about their child's traumatic experience contributed uniquely to symptoms at both time points. CONCLUSIONS: Parents of traumatized youth constitute a vulnerable group that has been overlooked in the literature. Intervention strategies following trauma should include both survivors and their parents. PMID- 26812594 TI - Visuo-manual coordination in preterm infants without neurological impairments. AB - The extent of and reasons for visuo-manual coordination deficits in moderate and late preterm born infants without neurological impairments are not well known. This paper presents a longitudinal study on the visuo-manual development of twelve preterm infants, born after 33-36 weeks of gestation without neurological complications, between the ages of 6 and 12 months. Visuo-manual integration and grasping were assessed using the Peabody Developmental Motor Scales, along with bimanual coordination and handedness tests. Visual function was examined once prior to the beginning of the study. Gross motor development was also evaluated every month. Preterm infants were compared to a control group of ten full-term infants according to corrected age. Compared to full-terms, the visual perception of preterm infants was close to normal, with only a measure of visual fixation lower than in full-terms. In contrast, preterm infants had delayed development of visuo-manual integration, grasping, bimanual coordination, and handedness even when compared using corrected age. Tonicity and gestational age at birth were the main variables associated to the delays. These results are discussed in terms of the possible factors underlying such delays. They need to be confirmed on a larger sample of preterm born children, and to be correlated with later development. This would allow developing markers of future neuropsychological impairments during childhood. PMID- 26812595 TI - Vocabulary skills are well developed in university students with dyslexia: Evidence from multiple case studies. AB - Most studies in adults with developmental dyslexia have focused on identifying the deficits responsible for their persistent reading difficulties, but little is known on how these readers manage the intensive exposure to written language required to obtain a university degree. The main objective of this study was to identify certain skills, and specifically vocabulary skills, that French university students with dyslexia have developed and that may contribute to their literacy skills. We tested 20 university students with dyslexia and 20 normal readers (matched on chronological age, gender, nonverbal IQ, and level of education) in reading, phonological, vocabulary breadth (number of known words), and vocabulary depth (accuracy and precision) tasks. In comparing vocabulary measures, we used both Rasch model and single case study methodologies. Results on reading and phonological tasks confirmed the persistence of deficits in written word recognition and phonological skills. However, using the Rasch model we found that the two groups performed at the same level in the vocabulary breadth task, whereas dyslexics systematically outperformed their chronological age controls in the vocabulary depth task. These results are supplemented by multiple case studies. The vocabulary skills of French university students with dyslexia are well developed. Possible interpretations of these results are discussed. PMID- 26812596 TI - Change in Adverse Events After Enrollment in the National Surgical Quality Improvement Program: A Systematic Review and Meta-Analysis. AB - BACKGROUND: The American College of Surgeons' National Surgical Quality Improvement Program (NSQIP) is the first nationally validated, risk-adjusted, outcomes-based program to measure and compare the quality of surgical care across North America. Participation in this program may provide an opportunity to reduce the incidence of adverse events related to surgery. STUDY DESIGN: A systematic review of the literature was performed. MedLine, EMBASE and PubMed were searched for studies relevant to NSQIP. Patient characteristics, intervention, and primary outcome measures were abstracted. The intervention was participation in NSQIP and monitoring of Individual Site Summary Reports with or without implementation of a quality improvement program. The outcomes of interest were change in peri operative adverse events and mortality represented by pooled risk ratios (pRR) and 95% confidence intervals (CI). RESULTS: Eleven articles reporting on 35 health care institutions were included. Nine (82%) of the eleven studies implemented a quality improvement program. Minimal improvements in superficial (pRR 0.81; 95% CI 0.72-0.91), deep (pRR 0.82; 95% CI0.64-1.05) and organ space (pRR 1.15; 95% CI 0.96-1.37) infections were observed at centers that did not institute a quality improvement program. However, centers that reported formal interventions for the prevention and treatment of infections observed substantial improvements (superficial pRR 0.55, 95% CI 0.39-0.77; deep pRR 0.61, 95% CI 0.50 0.75, and organ space pRR 0.60, 95% CI 0.50-0.71). Studies evaluating other adverse events noted decreased incidence following NSQIP participation and implementation of a formal quality improvement program. CONCLUSIONS: These data suggest that NSQIP is effective in reducing surgical morbidity. Improvement in surgical quality appears to be more marked at centers that implemented a formal quality improvement program directed at the reduction of specific morbidities. PMID- 26812597 TI - Physical Condition Does Not Affect Gravity-Induced Loss of Consciousness during Human Centrifuge Training in Well-Experienced Young Aviators. AB - BACKGROUND: Consensus on whether physical condition affects the risk of gravity induced loss of consciousness (G-LOC) has not been reached, and most previous studies about the issue did not include well-experienced aviators. We compared the physical conditions of well-experienced young aviators according to the occurrence of G-LOC during human centrifuge training. METHODS: Among 361 young male aviators on active flight duty with experience in high performance aircrafts for at least 2 years, 350 had full data available and were reviewed in this study. We divided the aviators into the G-LOC group and the non-G-LOC group according to their human centrifuge training results. We then compared their basic characteristics, body composition, physical fitness level, and pulmonary function. RESULTS: Twenty nine aviators (8.3%) who experienced G-LOC during human centrifuge training in their first trials were classified into the G-LOC group. There was no difference in physical condition of aviators between the two groups. CONCLUSIONS: Young aviators with experience in G-LOC showed no difference in physical condition such as muscle mass, strength, and general endurance from the aviators with no such experience. Although more studies are needed, physical condition does not seem to be a significant determinant of G-LOC among the experienced aviators. PMID- 26812598 TI - Heavy snow: IR spectroscopy of isotope mixed crystalline water ice. AB - Mid-infrared spectra have been measured for crystalline water ice aerosols of widely varied H/D isotopic composition. Particles with diameters ranging from 10 200 nm were generated via rapid collisional cooling with a cold buffer gas over a range of temperatures from 7-200 K. In near isotopically pure ices, the nuL band position is slightly red-shifted with increasing temperature whilst in the nu2 region apparently anomalous shifts in peak maxima are explained by the contribution of a broad 2nuL band of H2O and a 3nuL band of D2O together with nu2 intensity that is particularly weak in low temperature crystalline ice. The hydrogen bonded OH (or OD) oscillator bands of near pure H2O (or D2O) ices are blue-shifted with temperature, with a gradient very similar to that of the corresponding band in isotope diluted samples, HOD in D2O (or H2O). It implies that this observed temperature trend is predominantly due to the intrinsic change in local hydride stretch potential energy, rather than to changes in intermolecular coupling. However, it is also observed that the narrow hydride stretch bands of an isotope diluted sample rapidly develop sub-band structure as the oscillator concentration increases, evidence of strong intermolecular coupling and a high degree of delocalisation. Anomalous blue-shifts in the OD stretch profile as D2O concentration grows is attributable to Fermi resonance with 2nu2 of D2O, in much closer proximity than the corresponding H2O levels. Theoretical results from a mixed quantum/classical approach are used to validate these findings in the hydride stretching region. Theory qualitatively reproduces the experimental trends as a function of temperature and isotopic variance. PMID- 26812599 TI - Blastomyces gilchristii as Cause of Fatal Acute Respiratory Distress Syndrome. AB - Since the 2013 description of Blastomyces gilchristii, research describing the virulence or clinical outcome of B. gilchristii infection has been lacking. We report molecular evidence of B. gilchristii as an etiologic agent of fatal acute respiratory distress syndrome. B. gilchristii infection was confirmed by PCR and sequence analysis. PMID- 26812600 TI - High-level expression and purification of the major house dust mite allergen Der p 2 in Escherichia coli. AB - Der p 2, a major allergen derived from the house dust mite Dermatophagoides pteronyssinus, is one of the most clinically relevant allergens worldwide. Recombinant Der p 2 (rDer p 2) is useful in clinical diagnosis and disease specific immunotherapy. However, previous studies showed that Der p 2 can only be expressed in Escherichia coli (E. coli) cells as inclusion bodies, thus protein refolding is required to obtain functional products. Here we report a new method to produce biologically active Der p 2 protein in E. coli. N-terminal hexahistidine- and trigger factor (TF)-tagged Der p 2 was expressed in soluble form in E. coli and purified using a combination of chromatography processes. This procedure produced milligram-level high purity Der p 2 per liter of bacterial culture. Moreover, far-UV region circular dichroism (CD) analysis and serum specific IgE reactivity test demonstrated that the secondary structure and IgE reactivity properties of rDer p 2 produced in our study were almost identical to those of natural Der p 2 (nDer p 2). In conclusion, the method developed in this work provides a useful tool for the production of immunologically active recombinant Der p 2 for clinical applications. PMID- 26812601 TI - Computational Tension Mapping of Adherent Cells Based on Actin Imaging. AB - Forces transiting through the cytoskeleton are known to play a role in adherent cell activity. Up to now few approaches haves been able to determine theses intracellular forces. We thus developed a computational mechanical model based on a reconstruction of the cytoskeleton of an adherent cell from fluorescence staining of the actin network and focal adhesions (FA). Our custom made algorithm converted the 2D image of an actin network into a map of contractile interactions inside a 2D node grid, each node representing a group of pixels. We assumed that actin filaments observed under fluorescence microscopy, appear brighter when thicker, we thus presumed that nodes corresponding to pixels with higher actin density were linked by stiffer interactions. This enabled us to create a system of heterogeneous interactions which represent the spatial organization of the contractile actin network. The contractility of this interaction system was then adapted to match the level of force the cell truly exerted on focal adhesions; forces on focal adhesions were estimated from their vinculin expressed size. This enabled the model to compute consistent mechanical forces transiting throughout the cell. After computation, we applied a graphical approach on the original actin image, which enabled us to calculate tension forces throughout the cell, or in a particular region or even in single stress fibers. It also enabled us to study different scenarios which may indicate the mechanical role of other cytoskeletal components such as microtubules. For instance, our results stated that the ratio between intra and extra cellular compression is inversely proportional to intracellular tension. PMID- 26812604 TI - Yeast-Based High-Throughput Screens to Identify Novel Compounds Active against Brugia malayi. AB - BACKGROUND: Lymphatic filariasis is caused by the parasitic worms Wuchereria bancrofti, Brugia malayi or B. timori, which are transmitted via the bites from infected mosquitoes. Once in the human body, the parasites develop into adult worms in the lymphatic vessels, causing severe damage and swelling of the affected tissues. According to the World Health Organization, over 1.2 billion people in 58 countries are at risk of contracting lymphatic filariasis. Very few drugs are available to treat patients infected with these parasites, and these have low efficacy against the adult stages of the worms, which can live for 7-15 years in the human body. The requirement for annual treatment increases the risk of drug-resistant worms emerging, making it imperative to develop new drugs against these devastating diseases. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a yeast-based, high-throughput screening system whereby essential yeast genes are replaced with their filarial or human counterparts. These strains are labeled with different fluorescent proteins to allow the simultaneous monitoring of strains with parasite or human genes in competition, and hence the identification of compounds that inhibit the parasite target without affecting its human ortholog. We constructed yeast strains expressing eight different Brugia malayi drug targets (as well as seven of their human counterparts), and performed medium-throughput drug screens for compounds that specifically inhibit the parasite enzymes. Using the Malaria Box collection (400 compounds), we identified nine filarial specific inhibitors and confirmed the antifilarial activity of five of these using in vitro assays against Brugia pahangi. CONCLUSIONS/SIGNIFICANCE: We were able to functionally complement yeast deletions with eight different Brugia malayi enzymes that represent potential drug targets. We demonstrated that our yeast-based screening platform is efficient in identifying compounds that can discriminate between human and filarial enzymes. Hence, we are confident that we can extend our efforts to the construction of strains with further filarial targets (in particular for those species that cannot be cultivated in the laboratory), and perform high-throughput drug screens to identify specific inhibitors of the parasite enzymes. By establishing synergistic collaborations with researchers working directly on different parasitic worms, we aim to aid antihelmintic drug development for both human and veterinary infections. PMID- 26812605 TI - Serum Levels of Coenzyme Q10 in Patients with Multiple System Atrophy. AB - The COQ2 gene encodes an essential enzyme for biogenesis, coenzyme Q10 (CoQ10). Recessive mutations in this gene have recently been identified in families with multiple system atrophy (MSA). Moreover, specific heterozygous variants in the COQ2 gene have also been reported to confer susceptibility to sporadic MSA in Japanese cohorts. These findings have suggested the potential usefulness of CoQ10 as a blood-based biomarker for diagnosing MSA. This study measured serum levels of CoQ10 in 18 patients with MSA, 20 patients with Parkinson's disease and 18 control participants. Although differences in total CoQ10 (i.e., total levels of serum CoQ10 and its reduced form) among the three groups were not significant, total CoQ10 level corrected by serum cholesterol was significantly lower in the MSA group than in the Control group. Our findings suggest that serum CoQ10 can be used as a biomarker in the diagnosis of MSA and to provide supportive evidence for the hypothesis that decreased levels of CoQ10 in brain tissue lead to an increased risk of MSA. PMID- 26812602 TI - Hip Joint Stresses Due to Cam-Type Femoroacetabular Impingement: A Systematic Review of Finite Element Simulations. AB - BACKGROUND: The cam deformity causes the anterosuperior femoral head to obstruct with the acetabulum, resulting in femoroacetabular impingement (FAI) and elevated risks of early osteoarthritis. Several finite element models have simulated adverse loading conditions due to cam FAI, to better understand the relationship between mechanical stresses and cartilage degeneration. Our purpose was to conduct a systematic review and examine the previous finite element models and simulations that examined hip joint stresses due to cam FAI. METHODS: The systematic review was conducted to identify those finite element studies of cam type FAI. The review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and studies that reported hip joint contact pressures or stresses were included in the quantitative synthesis. RESULTS: Nine articles studied FAI morphologies using finite element methods and were included in the qualitative synthesis. Four articles specifically examined contact pressures and stresses due to cam FAI and were included in the quantitative synthesis. The studies demonstrated that cam FAI resulted in substantially elevated contact pressures (median = 10.4 MPa, range = 8.5-12.2 MPa) and von Mises stresses (median 15.5 MPa, range = 15.0-16.0 MPa) at the acetabular cartilage; and elevated maximum-shear stress on the bone (median = 15.2 MPa, range = 14.3-16.0 MPa), in comparison with control hips, during large amplitudes of hip motions. Many studies implemented or adapted idealized, ball-and-cup, parametric models to predict stresses, along with homogeneous bone material properties and in vivo instrumented prostheses loading data. CONCLUSION: The formulation of a robust subject-specific FE model, to delineate the pathomechanisms of FAI, remains an ongoing challenge. The available literature provides clear insight into the estimated stresses due to the cam deformity and provides an assessment of its risks leading to early joint degeneration. PMID- 26812606 TI - Comparing the length of penile mucosa in men with and without premature ejaculation. AB - BACKGROUND: Premature ejaculation is one of the prevalent disorders in men; almost one out of three men between 18 and 59 years old have this disorder with its leading sequel such as lack of self-confidence, anxiety, depression and unsatisfactory intercourse in men and their partners. This study aimed to compare the length of penile mucosa in men with and without premature ejaculation. METHOD: Three hundred and eighty patients referring to our hospital from March 2009 to March 2010 were enrolled in the study. First group comprised 190 men with premature ejaculation and second group included 190 men without premature ejaculation as control group that were chosen randomly. A questionnaire was designed to collect data and was completed for both groups. Height, weight, body mass index (BMI), length of penile mucosa, length of penis and intravaginal ejaculation latency time (IELT) were measured. RESULTS: The mean IELT in premature ejaculation group and control group were 47.58 +/- 29.55 and 410.38 +/- 190.2 s, respectively (p = 0.001). The mean penis length in premature ejaculation group and control group were 127.25 +/- 16.23 and 127.03 +/- 17.42 mm, respectively (p = 0.901, with nonsignificant difference); the mean penile mucosa in premature ejaculation group was 33.83 +/- 11.54 mm and in control group was 31.40 +/- 11.97 mm (p = 0.014, with significant difference). CONCLUSION: Longer penile mucosa can be one of the factors in causing premature ejaculation. PMID- 26812608 TI - Limitation of Symptoms as Predictors of Remission in Eosinophilic Esophagitis: The Need to Go Beyond Endoscopy and Histology. PMID- 26812609 TI - Family History of Colorectal Adenomas: Taking the Methodological Bull by the Horns. PMID- 26812607 TI - Type I interferons in viral control and immune regulation. AB - Type 1 interferons (IFN-I) exert pleiotropic biological effects during viral infections, all which contribute to balancing virus control and immune pathology. Despite extensive antiviral functions that subdue virus replication, recent studies demonstrate pathogenic and pro-viral roles for IFN-I signaling during acute and persistent virus infection. IFN-I signaling can promote morbidity and mortality through induction of aberrant inflammatory responses during acute viral infection. In contrast, IFN-I signaling during persistent viral infection supports immune suppression, lymphoid tissue disorganization and CD4 T cell dysfunction. Systematic characterization of the cellular populations and intricacies of IFN-I signaling that promote pathology or immune suppression during acute and persistent viral infections, respectively, should inform the development of treatments and modalities to control viral associated pathologies. PMID- 26812610 TI - Surface decorated nanoparticles as surrogate carriers for improved transport and absorption of epirubicin across the gastrointestinal tract: Pharmacokinetic and pharmacodynamic investigations. AB - Epirubicin (EPI) is a P-gp substrate antracycline analogue which elicits poor oral bioavailability. In the present work, EPI loaded poly-lactide-co-glycolic acid nanoparticles (PLGA-NPs) were prepared by double emulsion approach and superficially decorated with polyethylene glycol (EPI-PNPs) and mannosamine (EPI MNPs). Average hydrodynamic particle size of EPI-PNPs and EPI-MNPs was found 248.63 +/- 12.36 and 254.23 +/- 15.16 nm, respectively. Cytotoxicity studies were performed against human breast adenocarcinoma cell lines (MCF-7) confirmed the superiority of EPI-PNPs and EPI-MNPs over free epirubicin solution (EPI-S). Further, confocal laser scanning microscopy (CLSM) and flow cytometric analysis (FACS) demonstrated enhanced drug uptake through EPI-PNPs and EPI-MNPs and elucidated dominance of caveolae mediated endocytosis for NPs uptake. Cellular transport conducted on human colon adenocarcinoma cell line (Caco-2) showed 2.45 and 3.17 folds higher permeability of EPI through EPI-PNPs and EPI-MNPs when compared with EPI-S (p<0.001) while permeability of EPI was found 5.23 and 5.67 folds higher across rat ileum, respectively. Furthermore, pharmacokinetic studies demonstrated 4.7 and 5.57 folds higher oral bioavailability through EPI-PNPs and EPI-MNPs when compared with EPI-S. In addition, both, EPI-PNPs and EMNPs showed tumor suppression comparable to indicated route (i.v. injection). EPI-MNPs showed 1.18 folds higher bioavailability and better tumor suppression than EPI-PNPs. PMID- 26812611 TI - The effects of strength training and raloxifene on bone health in aging ovariectomized rats. AB - The aim of this study was to investigate the effects of strength training (ST) and raloxifene (Ral), alone or in combination, on the prevention of bone loss in an aging estrogen-deficient rat model. Aging Wistar female rats were ovariectomized at 14months and allocated to four groups: (1) non-trained and treated with vehicle, NT-Veh; (2) strength training and treated with vehicle, ST Veh; (3) non-trained and treated with raloxifene, NT-Ral; and (4) strength training and treated with raloxifene, ST-Ral. ST was performed on a ladder three times per week and Ral was administered daily by gavage (1mg/kg/day), both for 120days. Areal bone mineral density (aBMD), strength, microarchitecture, and biomarkers (osteocalcin, OCN; osteoprotegerin, OPG; and tartrate-resistant acid phosphatase, TRAP) were assessed. Immunohistochemistry was performed for runt related transcription factor 2 (RUNX2), osterix (OSX), OCN, OPG, TRAP, and receptor activator of nuclear factor kappa-B ligand (RANKL). The rats that performed ST (ST-Veh) or were treated with Ral (NT-Ral) showed significant improvements in aBMD (p=0.001 and 0.004), bone strength (p=0.001), and bone microarchitecture, such as BV/TV (%) (p=0.001), BS/TV (mm(2)/mm(3)) (p=0.023 and 0.002), Conn.Dn (1/mm(3)) (p=0.001), Tb.N (1/mm) (p=0.012 and 0.011), Tb.Th (1/mm) (p=0.001), SMI (p=0.001 and 0.002), Tb.Sp (p=0.001), and DA (p=0.002 and 0.007); there was also a significant decrease in plasma levels of OCN (p=0.001 and 0.002) and OPG (p=0.003 and 0.014), compared with animals in the NT-Veh group. Ral, with or without ST, promoted an increased immunolabeling pattern for RUNX2 (p=0.0105 and p=0.0006) and OSX (p=0.0105), but a reduced immunolabeling pattern for TRAP (p=0.0056) and RANKL (p=0.033 and 0.004). ST increased the immunolabeling pattern for RUNX2 (p=0.0105), and association with Ral resulted in an increased immunolabeling pattern for OPG (p=0.0034) and OCN (p=0.0024). In summary, ST and Ral administration in aged, estrogen-deficient Wistar female rats is associated with a decrease in bone turnover marker plasma levels, increased activity of cells that promote osteoblastogenesis, and decreased activity of cells that promote osteoclastogenesis; these are correlated with higher aBMD, bone strength, and bone microarchitecture at the femoral neck. The results indicate that strength training and Ral are potential tools to reduce the risk of fractures at clinically relevant sites. PMID- 26812612 TI - Inflammatory mediators in osteoarthritis: A critical review of the state-of-the art, current prospects, and future challenges. AB - Osteoarthritis (OA) has traditionally been defined as a prototypical non inflammatory arthropathy, but today there is compelling evidence to suggest that it has an inflammatory component. Many recent studies have shown the presence of synovitis in a large number of patients with OA and demonstrated a direct association between joint inflammation and the progression of OA. Pro inflammatory cytokines, reactive oxygen species (ROS), nitric oxide, matrix degrading enzymes and biomechanical stress are major factors responsible for the progression of OA in synovial joints. The aim of this review is to discuss the significance of a wide range of implicated inflammatory mediators and their contribution to the progression of OA. We also discuss some of the currently available guidelines, practices, and prospects. In addition, this review argues for new innovation in methodologies and instrumentation for the non-invasive detection of inflammation in OA by modern imaging techniques. We propose that identifying early inflammatory events and targeting these alterations will help to ameliorate the major symptoms such as inflammation and pain in OA patients. PMID- 26812613 TI - Executive functions improvement following a 5-month aquaerobics program in older adults: Role of cardiac vagal control in inhibition performance. AB - The aims of this study were to examine the effects of aerobic exercise on measures of executive performance and their relationships with changes in cardiorespiratory fitness, cardiac vagal control (heart rate variability) and psychological variables. Thirty-six sedentary seniors aged 60-75 years were randomly assigned to a swimming and aquaerobics program or a stretching program two times a week for 21 weeks. Executive functions (inhibition, updating of working memory and cognitive flexibility) and cardiorespiratory fitness (estimated VO2max) were assessed at the start, after 10 weeks of program and at the end of the program. Resting HRV and measures of psychological outcomes (depression, self-efficacy, decisional balance) were obtained at the start and at the end of the program. Participants of both groups significantly improved their VO2max level, their psychological state and their performance for the 2-back task. Only the participants in the aquaerobics group significantly improved their vagally-mediated HRV and their performance for the Stroop test and the verbal running-span test at the end of the program. Only improvements in cardiac vagal control and in inhibition were shown to be functionally related. These results are discussed in line with the model of neurovisceral integration. PMID- 26812614 TI - Otologic and Rhinologic Manifestations of Eosinophilic Granulomatosis with Polyangiitis. AB - BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic autoimmune disease that manifests as asthma, recurrent sinusitis and peripheral eosinophilia. In this study, we investigated the clinical features of the ear and nasal manifestations of EGPA in comparison with those of granulomatosis with polyangiitis (GPA). MATERIALS AND METHODS: Twenty-one patients diagnosed with EGPA were studied. The frequency of otologic manifestations, the degree of hearing loss and the frequency of nasal symptoms were assessed. The onset of ear symptoms, sinusitis and asthma in patients with EGPA were also examined. RESULTS: Eleven patients (52.4%) with EGPA demonstrated otologic symptoms. The EGPA patients commonly presented mild-to-moderate mixed or sensorineural hearing loss. The pattern of hearing loss was mainly flat, and all but 1 patient achieved complete remission from their hearing impairments. Eighteen patients (85.7%) with EGPA demonstrated nasal symptoms. Patients with EGPA showed a significantly higher incidence of nasal polyps than did those with GPA. The median Lund and Mackey scoring system score was 13.7 for patients with EGPA, and ethmoid sinus shadows were more severe than those of the maxillary sinus. Most ear symptoms associated with EGPA were observed after definitive diagnosis, although sinusitis and asthma tended to manifest themselves before diagnosis. There were significant differences between the onset of ear symptoms and those of asthma and sinusitis. CONCLUSION: As over 80% of patients with EGPA had nasal symptoms and over half had ear symptoms, otolaryngologists should be aware of this disease. Recognition of the characteristic ear and nasal symptoms are thought to be particularly important to obtain an early diagnosis of EGPA. PMID- 26812615 TI - Predominance of Intrinsic Mechanism of Resting Heart Rate Control and Preserved Baroreflex Sensitivity in Professional Cyclists after Competitive Training. AB - Different season trainings may influence autonomic and non-autonomic cardiac control of heart rate and provokes specific adaptations on heart's structure in athletes. We investigated the influence of transition training (TT) and competitive training (CT) on resting heart rate, its mechanisms of control, spontaneous baroreflex sensitivity (BRS) and relationships between heart rate mechanisms and cardiac structure in professional cyclists (N = 10). Heart rate (ECG) and arterial blood pressure (Pulse Tonometry) were recorded continuously. Autonomic blockade was performed (atropine-0.04 mg.kg-1; esmolol-500 MUg.kg-1 = 0.5 mg). Vagal effect, intrinsic heart rate, parasympathetic (n) and sympathetic (m) modulations, autonomic influence, autonomic balance and BRS were calculated. Plasma norepinephrine (high-pressure liquid chromatography) and cardiac structure (echocardiography) were evaluated. Resting heart rate was similar in TT and CT. However, vagal effect, intrinsic heart rate, autonomic influence and parasympathetic modulation (higher n value) decreased in CT (P<=0.05). Sympathetic modulation was similar in both trainings. The autonomic balance increased in CT but still showed parasympathetic predominance. Cardiac diameter, septum and posterior wall thickness and left ventricular mass also increased in CT (P<0.05) as well as diastolic function. We observed an inverse correlation between left ventricular diastolic diameter, septum and posterior wall thickness and left ventricular mass with intrinsic heart rate. Blood pressure and BRS were similar in both trainings. Intrinsic heart rate mechanism is predominant over vagal effect during CT, despite similar resting heart rate. Preserved blood pressure levels and BRS during CT are probably due to similar sympathetic modulation in both trainings. PMID- 26812616 TI - Early-Stage Induction of SWI/SNF Mutations during Esophageal Squamous Cell Carcinogenesis. AB - The SWI/SNF chromatin remodeling complex is frequently inactivated by somatic mutations of its various components in various types of cancers, and also by aberrant DNA methylation. However, its somatic mutations and aberrant methylation in esophageal squamous cell carcinomas (ESCCs) have not been fully analyzed. In this study, we aimed to clarify in ESCC, what components of the SWI/SNF complex have somatic mutations and aberrant methylation, and when somatic mutations of the SWI/SNF complex occur. Deep sequencing of components of the SWI/SNF complex using a bench-top next generation sequencer revealed that eight of 92 ESCCs (8.7%) had 11 somatic mutations of 7 genes, ARID1A, ARID2, ATRX, PBRM1, SMARCA4, SMARCAL1, and SMARCC1. The SMARCA4 mutations were located in the Forkhead (85Ser>Leu) and SNF2 family N-terminal (882Glu>Lys) domains. The PBRM1 mutations were located in a bromodomain (80Asn>Ser) and an HMG-box domain (1,377Glu>Lys). For most mutations, their mutant allele frequency was 31-77% (mean 61%) of the fraction of cancer cells in the same samples, indicating that most of the cancer cells in individual ESCC samples had the SWI/SNF mutations on one allele, when present. In addition, a BeadChip array analysis revealed that a component of the SWI/SNF complex, ACTL6B, had aberrant methylation at its promoter CpG island in 18 of 52 ESCCs (34.6%). These results showed that genetic and epigenetic alterations of the SWI/SNF complex are present in ESCCs, and suggested that genetic alterations are induced at an early stage of esophageal squamous cell carcinogenesis. PMID- 26812617 TI - Validation of a Multiplex Allele-Specific Polymerase Chain Reaction Assay for Detection of KRAS Gene Mutations in Formalin-Fixed, Paraffin-Embedded Tissues from Colorectal Cancer Patients. AB - BACKGROUND: Patients with KRAS mutations do not respond to epidermal growth factor receptor (EGFR) inhibitors and fail to benefit from adjuvant chemotherapy. Mutation analysis of KRAS is needed before starting treatment with monoclonal anti-EGFR antibodies in patients with metastatic colorectal cancer (mCRC). The objective of this study is to develop a multiplex allele-specific PCR (MAS-PCR) assay to detect KRAS mutations. METHODS: We developed a single-tube MAS-PCR assay for the detection of seven KRAS mutations (G12D, G12A, G12R, G12C, G12S, G12V, and G13D). We performed MAS-PCR assay analysis for KRAS on DNA isolated from 270 formalin-fixed paraffin-embedded (FFPE) colorectal cancer tissues. Sequences of all 270 samples were determined by pyrosequencing. Seven known point-mutation DNA samples diluted with wild-type DNA were assayed to determine the limitation of detection and reproducibility of the MAS-PCR assay. RESULTS: Overall, the results of MAS-PCR assay were in good concordance with pyrosequencing, and only seven discordant samples were found. The MAS-PCR assay reproducibly detected 1 to 2% mutant alleles. The most common mutations were G13D in codon 13 (49.17%), G12D (25.83%) and G12V (12.50%) in codon 12. CONCLUSION: The MAS-PCR assay provides a rapid, cost-effective, and reliable diagnostic tool for accurate detection of KRAS mutations in routine FFPE colorectal cancer tissues. PMID- 26812618 TI - The Comparative Effects of Risperidone Long-Acting Injection and Paliperidone Palmitate on Social Functioning in Schizophrenia: A 6-Month, Open-Label, Randomized Controlled Pilot Trial. AB - PURPOSE: The aim of this study was to compare the effects of risperidone long acting injection (RLAI) and paliperidone palmitate (PP) on non-acute-phase social functioning in patients with schizophrenia. PATIENTS AND METHODS: In this 6-month pilot, open-label, randomized controlled study, 30 patients with schizophrenia who had been treated with RLAI were randomly allocated to the RLAI continuation group or switched to the PP group. Patients were evaluated at baseline and 6 months with the Social Functioning Scale (SFS) as the primary outcome variable and University of California San Diego Performance-Based Skills Assessment Brief (UPSA-B), Social Emotional Cognition Task (SECT), Positive and Negative Syndrome Scale (PANSS), and Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) scores as secondary outcomes. RESULTS: At baseline, the two groups did not significantly differ in demographic or clinical features. The two groups did not differ in total score changes for the UPSA-B, the SECT, the PANSS, and the DIEPSS. However, the total scores and the two subscales of the SFS, i.e. independence-competence and independence-performance, were more improved in the PP group compared to the RLAI group (total scores, p = 0.038; competence, p = 0.001, and performance, p = 0.007, respectively). CONCLUSION: These results suggest that PP may improve the total social functioning, independent life competence, and performance as compared to the RLAI group. However, these results are preliminary and need independent replication in larger samples before any definitive statement can be made. PMID- 26812619 TI - Molecular Motion and Conformational Interconversion of Ir(I).COD Included in Rebek's Self-Folding Octaamide Cavitand. AB - We report experimental and theoretical evidence of restrained axial rotation for heteroleptic L2.Ir(I).1,5-cyclooctadiene (COD) complexes included in the aromatic cavity of Rebek's self-folding octaamide cavitand. At 298 K, the axial spinning motion of the included organometallic guests was slow on the (1)H NMR time scale and produced a proton spectrum for the bound host indicative of C2 symmetry. Signals corresponding to aromatic protons of the bound host coalesced at 323 K, indicating that the spinning process of the included guest became fast on the (1)H NMR time scale and that the complex approached C4 symmetry. Surprisingly, lowering the temperature of the solution to 193 K induced an additional splitting of the proton signals observed at room temperature for both the bound host and the included guest. We propose the emergence of a new element of chirality in the complexes, which was associated with a slow interconversion, on the (1)H NMR time scale between the two chiral twisted-boat conformers of the chelated COD included in the already chiral cavity of the container. This leads to the inclusion complexes existing in solution as pairs of two racemic diastereomers. We estimated that the racemization barrier for the two cyclochiral conformers of the Ir(I) chelated COD was 5 kcal mol(-1) higher as an included organometallic complex than as free in solution. Furthermore, we performed a van't Hoff plot and determined that the inclusion of the organometallic complex in the cavitand was endothermic and exclusively driven by entropy (DeltaH = 5.9 kcal mol(-1) and DeltaS = 33.9 cal mol(-1) K(-1)). PMID- 26812620 TI - Direct Interfacial Modification of Nanocellulose Films for Thermoresponsive Membrane Templates. AB - This letter proposes a strategy to construct tunable films combining the physical characteristics of cellulose nanofibrils and smart polymers for membrane applications. A functional membrane template was obtained by first fabricating a water stable film from cellulose nanofibrils and subsequently surface grafting it with a thermoresponsive polymer, poly(N-isopropylacrylamide). The behavior of the membrane template was dependent on temperature. The increment in slope of relative water permeance around the lower critical solution temperature of poly(N isopropylacrylamide) increased from 18 to 100% upon polymer attachment. Although the membrane template essentially consisted of wood-based materials, the benefits of smart synthetic polymers were achieved. PMID- 26812622 TI - Iron-Catalyzed Allylic Amination Directly from Allylic Alcohols. AB - Allylic amination, directly from alcohols, has been demonstrated without any Lewis acid activators using an efficient and regiospecific molecular iron catalyst. Various amines and alcohols were employed and the reaction proceeded through the oxidation/reduction (redox) pathway. A direct one-step synthesis of common drugs, such as cinnarizine and nafetifine, was exhibited from cinnamyl alcohol that produced water as side product. PMID- 26812621 TI - RORalpha and 25-Hydroxycholesterol Crosstalk Regulates Lipid Droplet Homeostasis in Macrophages. AB - Nuclear hormone receptors have important roles in the regulation of metabolic and inflammatory pathways. The retinoid-related orphan receptor alpha (Roralpha) deficient staggerer (sg/sg) mice display several phenotypes indicative of aberrant lipid metabolism, including dyslipidemia, and increased susceptibility to atherosclerosis. In this study we demonstrate that macrophages from sg/sg mice have increased ability to accumulate lipids and accordingly exhibit larger lipid droplets (LD). We have previously shown that BMMs from sg/sg mice have significantly decreased expression of cholesterol 25-hydroxylase (Ch25h) mRNA, the enzyme that produces the oxysterol, 25-hydroxycholesterol (25HC), and now confirm this at the protein level. 25HC functions as an inverse agonist for RORalpha. siRNA knockdown of Ch25h in macrophages up-regulates Vldlr mRNA expression and causes increased accumulation of LDs. Treatment with physiological concentrations of 25HC in sg/sg macrophages restored lipid accumulation back to normal levels. Thus, 25HC and RORalpha signify a new pathway involved in the regulation of lipid homeostasis in macrophages, potentially via increased uptake of lipid which is suggested by mRNA expression changes in Vldlr and other related genes. PMID- 26812625 TI - Vectorborne Infections, Mali. PMID- 26812624 TI - Transplantation from a symptomatic carrier sister restores host defenses but does not prevent colitis in NEMO deficiency. AB - NF-kappaB essential modulator (NEMO) deficiency causes ectodermal dysplasia with immunodeficiency in males, while manifesting as incontinentia pigmenti in heterozygous females. We report a family with NEMO deficiency, in which a female carrier displayed skewed X-inactivation favoring the mutant NEMO allele associated with symptoms of Behcet's disease. Hematopoietic stem cell transplantation of an affected boy from this donor reconstituted an immune system with retained skewed X-inactivation. After transplantation no more severe infections occurred, indicating that an active wild-type NEMO allele in only 10% of immune cells restores host defense. Yet he developed inflammatory bowel disease (IBD). While gut infiltrating immune cells stained strongly for nuclear p65 indicating restored NEMO function, this was not the case in intestinal epithelial cells - in contrast to cells from conventional IBD patients. These results extend murine observations that epithelial NEMO-deficiency suffices to cause IBD. High anti-TNF doses controlled the intestinal inflammation and symptoms of Behcet's disease. PMID- 26812626 TI - Total Synthesis of (+)-Fusarisetin A Driven by a One-Pot Four-Reaction Process. AB - A concise, asymmetric total synthesis of (+)-fusarisetin A, a hybrid natural product, has been achieved. A one-pot four-reaction process efficiently delivered the tetracycle 2 which served as a key intermediate for the synthesis of the title natural product and its analogues through amino acid incorporation. PMID- 26812623 TI - DNA-based control of protein activity. AB - DNA has emerged as a highly versatile construction material for nanometer-sized structures and sophisticated molecular machines and circuits. The successful application of nucleic acid based systems greatly relies on their ability to autonomously sense and act on their environment. In this feature article, the development of DNA-based strategies to dynamically control protein activity via oligonucleotide triggers is discussed. Depending on the desired application, protein activity can be controlled by directly conjugating them to an oligonucleotide handle, or expressing them as a fusion protein with DNA binding motifs. To control proteins without modifying them chemically or genetically, multivalent ligands and aptamers that reversibly inhibit their function provide valuable tools to regulate proteins in a noncovalent manner. The goal of this feature article is to give an overview of strategies developed to control protein activity via oligonucleotide-based triggers, as well as hurdles yet to be taken to obtain fully autonomous systems that interrogate, process and act on their environments by means of DNA-based protein control. PMID- 26812628 TI - Approaches to Increasing Clinical Trial Access and Enrollment for Adolescents and Young Adults with Cancer. PMID- 26812627 TI - Pharmacological evaluation of the mechanisms involved in increased adiposity in zebrafish triggered by the environmental contaminant tributyltin. AB - One proposed contributing factor to the rise in overweight and obesity is exposure to endocrine disrupting chemicals. Tributyltin chloride (TBT), an organotin, induces adipogenesis in cell culture models and may increases adipose mass in vivo in vertebrate model organisms. It has been hypothesized that TBT acts via the peroxisome proliferator activated receptor (PPAR)gamma-dependent pathway. However, the mechanisms involved in the effects of TBT exposure on in vivo adipose tissue metabolism remain unexplored. Semitransparent zebrafish larvae, with their well-developed white adipose tissue, offer a unique opportunity for studying the effects of toxicant chemicals and pharmaceuticals on adipocyte biology and whole-organism adiposity in a vertebrate model. Within hours, zebrafish larvae, treated at environmentally-relevant nanomolar concentrations of TBT, exhibited a remarkable increase in adiposity linked to adipocyte hypertrophy. Under the experimental conditions used, we also demonstrated that zebrafish larvae adipose tissue proved to be highly responsive to selected human nuclear receptor agonists and antagonists. Retinoid X receptor (RXR) homodimers and RXR/liver X receptor heterodimers were suggested to be in vivo effectors of the obesogenic effect of TBT on zebrafish white adipose tissue. RXR/PPARgamma heterodimers may be recruited to modulate adiposity in zebrafish but were not a necessary requirement for the short term in vivo TBT obesogenic effect. Together, the present results suggest that TBT may induce the promotion of triacylglycerol storage in adipocytes via RXR-dependent pathways without necessary using PPAR isoforms. PMID- 26812629 TI - Challenges Conducting Qualitative Psychosocial Research for Adolescent and Young Adult Patients and Survivors. AB - The field of adolescent and young adult oncology (AYAO) is developing and evolving, providing fertile ground for debate, discussion, and the exchange of opinions. In the "Controversies" feature of each issue of Journal of Adolescent and Young Adult Oncology, we will pose a key AYAO question to people from various organizations, geographical locations, and professions. In this issue, we asked respondents about the challenges they encounter conducting qualitative psychosocial research for AYA patients and survivors. -Editors. PMID- 26812630 TI - Returning to School After Adolescent Cancer: A Qualitative Examination of Australian Survivors' and Their Families' Perspectives. AB - PURPOSE: To examine key factors related to adolescent cancer survivors' return to school after cancer treatment completion, which can be a time of complex transition. PATIENTS AND METHODS: Seventy semi-structured interviews were conducted with 19 adolescent cancer survivors (mean age 16.1 years), 21 mothers, 15 fathers, and 15 siblings from 22 Australian families. The conceptual framework of Miles and Huberman (1994) was employed to analyze interview data and emergent themes were organized using the software package QSR NVivo 8.0. RESULTS: Barriers to successful school re-entry included symptoms of fatigue, anxiety (particularly regarding examinations), and poor communication between families and the broader school community. Changing grade or school typically extinguished pre-existing support networks and was perceived by parents as a period of unmet need. Support from friends, teachers, tutors, and the hospital outreach nurse were seen as instrumental in creating a positive school re-entry experience. However, the majority of participants reported that support from the school counselor was minimal. Siblings reported this period as relatively non-impactful regarding their own education. CONCLUSIONS: Additional support is needed to help parents navigate the education system and to advocate effectively for their child's academic needs beyond the immediate re-entry period. There is strong potential for school counselors to increase the level of support they provide adolescents and their parents during the school re-entry period. The impact of this period on siblings' education is under-studied and warrants further research. PMID- 26812631 TI - Examination of the Increase in Thyroid Cancer Incidence Among Younger Women in the United States by Age, Race, Geography, and Tumor Size, 1999-2007. AB - PURPOSE: Thyroid cancer incidence has been increasing for several decades, but the reasons are not fully understood. Previous surveillance reports have covered less than 26% of the U.S. POPULATION: More recent, nationwide data are needed. This study examines thyroid cancer incidence among younger women by age, race/ethnicity, geography, and tumor size. PATIENTS AND METHODS: Our study uses nationwide surveillance data to describe incidence rates and recent trends in thyroid cancer among adults aged 20-39 years in the United States during 1999 2007, with a focus on females. RESULTS: Incidence rates were more than five times higher among females (16.4 per 100,000; 95% confidence interval [CI]: 16.2-16.6) than among males (3.1 per 100,000; 95% CI: 3.1-3.2). Among females, rates were higher among non-Hispanic whites than among other racial/ethnic groups and higher in the Northeast compared with other regions (p<0.05). During 1999-2007, incidence rates increased 5.3% each year among females (95% CI: 4.7-5.9). This increase was observed across five-year age groups, racial/ethnic groups (except American Indians/Alaska Natives), geographic regions, and tumor sizes. CONCLUSION: The increase in rates across all tumor sizes suggests that the observed increases cannot be attributed solely to changes in diagnostics or surveillance. In addition, the continued increase in incidence rates in recent years among persons born after 1960 suggests that other, more contemporary factors than those previously proposed may play a contributing role. PMID- 26812632 TI - Consolidative Proton Therapy Following High-dose Chemotherapy and Autologous Stem Cell Transplant in an Adolescent with Relapsed Hodgkin Lymphoma. AB - We present a case of an adolescent male with relapsed Hodgkin lymphoma involving the mediastinum two years following chemotherapy without radiotherapy. The patient was treated with second-line chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant and then presented for evaluation of consolidative involved-field proton therapy (PT). Comparative treatment plans were developed with three-dimensional X-ray radiotherapy (3DXRT) and PT. PT substantially reduced the dose to the lungs, heart, esophagus, and total body compared with 3DXRT, resulting in treatment with PT. PT should reduce the risk of late side effects compared with 3DXRT, including secondary malignancies and cardiovascular disease. PMID- 26812633 TI - Intergroup Trial C10403: A Pediatric Treatment Approach to Improve Outcomes in Adolescents and Young Adults with Acute Lymphoblastic Leukemia. PMID- 26812634 TI - [Not Available]. PMID- 26812635 TI - Dish-like drying patterns of the water-soluble gelatin sheet wetted by an aqueous droplet. AB - Drying dissipative patterns of the water-soluble gelatin sheet wetted by an aqueous droplet were observed as a function of time elapsed. The arrayed clusters of dishes formed at the broad ring area and grew outward toward multiple arrays with time. The drying patterns formed by the cooperative contribution of wetting, swelling, dissolving, evaporative, convectional, sedimentary and solidifying processes. Drying patterns were studied also for aqueous ethanol, aqueous NaCl solutions and dispersions of colloidal silica and poly(methyl methacrylate) spheres. The dish patterns were observed for the water-soluble substrates, for the first time, in this work. PMID- 26812636 TI - PEGylated polyethylenimine-entrapped gold nanoparticles modified with folic acid for targeted tumor CT imaging. AB - Development of various cost-effective contrast agents for targeted tumor computed tomography (CT) imaging still remains a great challenge. Herein, we present a facile approach to forming folic acid (FA)-targeted multifunctional gold nanoparticles (AuNPs) using cost-effective branched polyethylenimine (PEI) modified with polyethylene glycol (PEG) as a template for tumor CT imaging applications. In this work, PEI sequentially modified with PEG monomethyl ether, FA-linked PEG, and fluorescein isothiocyanate was used as a template to synthesize AuNPs, followed by transformation of the remaining PEI surface amines to acetamides. The formed FA-targeted PEI-entrapped AuNPs (FA-Au PENPs) were fully characterized. We show that the formed FA-Au PENPs with an Au core size of 2.1 nm are water soluble, colloidally stable, and non-cytotoxic in a given concentration range. Flow cytometry and confocal microscopy data reveal that the FA-Au PENPs are able to target cancer cells overexpressing FA receptors (FAR). Importantly, the developed FA-Au PENPs can be used as a nanoprobe for targeted CT imaging of FAR-expressing cancer cells in vitro and the xenografted tumor model in vivo. With the demonstrated biocompatibility by organ biodistribution and histological studies, the designed FA-Au PENPs may hold great promise to be used as a nanoprobe for CT imaging of different FAR-overexpressing tumors. PMID- 26812637 TI - Effect of interfacial properties on the activation volume of adsorbed enzymes. AB - We have studied the enzymatic activities of alpha-chymotrypsin (alpha-CT) and horseradish peroxidase (HRP) that are adsorbed on various chemically modified planar surfaces under aqueous solution. The enzymes were adsorbed on bare quartz, hydrophobic poly(styrene) (PS), positively charged poly(allylamine hydrochloride) (PAH), and negatively charged poly(styrene sulfonate) (PSS). Activation volumes of the enzymes at the aqueous-solid interfaces were determined by using high pressure total internal reflection fluorescence (TIRF) spectroscopy. Apparently, the pressure response of the adsorbed enzymes strongly depends on the interfacial properties. alpha-CT can be activated by pressure (increasing enzymatic rate) on negatively charged surfaces like quartz and PSS, whereas HRP is activated by pressure on hydrophobic PS. Corresponding negative activation volumes of -29 mL mol(-1) for alpha-CT on quartz, -23 mL mol(-1) for alpha-CT on PSS, and -35 mL mol(-1) for HRP on PS are found. In addition, the absolute activities of alpha-CT and HRP on quartz, PS, PAH and PSS were determined by UV absorption at ambient pressure. Remarkably, large activities are found on those surfaces that are associated with negative activation volumes. However, Fourier transform infrared (FTIR) spectra collected in attenuated total reflection (ATR) mode do not indicate major adsorption induced conformational changes of the enzymes at any interface studied. Overall, the results of this study show that the activity of immobilized enzymes can largely be enhanced by the right combination of adsorbent material and applied pressure. PMID- 26812638 TI - Direct chemical grafted curcumin on halloysite nanotubes as dual-responsive prodrug for pharmacological applications. AB - Covalently functionalized halloysite nanotubes (HNTs) were successfully employed as dual-responsive nanocarriers for curcumin (Cur). Particularly, we synthesized HNT-Cur prodrug with a controlled curcumin release on dependence of both intracellular glutathione (GSH) and pH conditions. In order to obtain HNT-Cur produgs, halloysite was firstly functionalized with cysteamine through disulphide linkage. Afterwards, curcumin molecules were chemically conjugated to the amino end groups of halloysite via Schiff's base formation. The successful functionalization of halloysite was proved by thermogravimetric analysis, FT-IR spectroscopy, dynamic light scattering and scanning electron microscopy. Experimental data confirmed the presence of curcumin on HNT external surface. Moreover, we investigated the kinetics of curcumin release by UV-vis spectroscopy, which highlighted that HNT-Cur prodrug possesses dual stimuli responsive ability upon exposure to GSH-rich or acidic environment. In vitro antiproliferative and antioxidant properties of HNT-Cur prodrug were studied with the aim to explore their potential applications in pharmaceutics. This work puts forward an efficient strategy to prepare halloysite based nanocarriers with controlled drug delivery capacity through direct chemical grafting with stimuli responsive linkage. PMID- 26812639 TI - Cross-linked polystyrene sulfonic acid and polyethylene glycol as a low-fouling material. AB - A negatively charged hydrophilic low fouling film was prepared by thermally cross linking a blend consisting of polystyrene sulfonic acid (PSS) and polyethylene glycol (PEG). The film was found to be stable by dip-washing. The fouling resistance of this material toward bacterial (Escherichia coli) and colloidal (polystyrene particles) attachment, non-specific protein (fibronectin) adsorption and cell (3T3 NIH) adhesion was evaluated and was compared with glass slides modified with polyethylene glycol (PEG) brushes, oxidized 3 mercaptopropyltrimethoxysilane (sulfonic acid, SA), and n octadecyltrichlorosilane (OTS). The extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory and thermodynamic models based on surface energy were used to explain the interaction behaviors of E. coli/polystyrene particles-substrate and protein-substrate interactions, respectively. The cross-linked PSS-PEG film was found to be slightly better than SA and PEG toward resisting non-specific protein adsorption, and showed comparable low attachment results as those of PEG toward particle, bacterial and NIH-3T3 cells adhesion. The low-fouling performance of PSS-PEG, a cross-linked film by a simple thermal curing process, could allow this material to be used for applications in aqueous environments, where most low fouling hydrophilic polymers, such as PSS or PEG, could not be easily retained. PMID- 26812640 TI - The International Scene in 2016: Biopreservation and Biobanking and ISBER. PMID- 26812641 TI - Impairment of arterial elastic properties and elevated circulating levels of transforming growth factor-beta in subjects with repaired coarctation of aorta. PMID- 26812642 TI - Sudden cardiac death in neuromuscolar disorders: Time to establish shared protocols for cardiac pacing. PMID- 26812645 TI - Feasibility of an Early Discontinuation of Thyroid Hormone Treatment in Very-Low Birth-Weight Infants at Risk for Transient or Permanent Congenital Hypothyroidism. AB - BACKGROUND/AIMS: This prospective study was conducted to investigate the feasibility of an early discontinuation of thyroid hormone treatment in very-low birth-weight (VLBW) infants with congenital hypothyroidism (CH). METHODS: We enrolled VLBW infants between January 2011 and December 2012. The infants were divided into the hypothyroid and normal thyroid function groups according to the results of a thyroid function test. We performed an early off-therapy trial at 24 months of age. RESULTS: Of the 182 VLBW infants enrolled, 15 were lost to follow up and 167 were finally enrolled. In total, 24 infants (14.4%) were assigned to the hypothyroid function group and were treated with thyroid hormone. Younger gestational age and a lower birth weight were associated with hypothyroid function. In the hypothyroid function group, hypothyroidism (HT) and hyperthyrotropinemia (HTT) were observed in 13 and 11 infants, respectively. There were no differences in the clinical characteristics between the HT and HTT groups. Overall, 24 infants discontinued thyroxine medication at 24 months of age after normal results had been confirmed by radiologic work-ups, including thyroid ultrasonography and technetium-99m scans. All infants were successfully weaned off thyroxine and maintained euthyroid function. CONCLUSION: Early discontinuation of thyroid hormone replacement therapy is possible in the majority of VLBW infants with CH. PMID- 26812643 TI - Exploring potential mortality reductions in 9 European countries by improving diet and lifestyle: A modelling approach. AB - BACKGROUND: Coronary heart disease (CHD) death rates have fallen across most of Europe in recent decades. However, substantial risk factor reductions have not been achieved across all Europe. Our aim was to quantify the potential impact of future policy scenarios on diet and lifestyle on CHD mortality in 9 European countries. METHODS: We updated the previously validated IMPACT CHD models in 9 European countries and extended them to 2010-11 (the baseline year) to predict reductions in CHD mortality to 2020(ages 25-74years). We compared three scenarios: conservative, intermediate and optimistic on smoking prevalence (absolute decreases of 5%, 10% and 15%); saturated fat intake (1%, 2% and 3% absolute decreases in % energy intake, replaced by unsaturated fats); salt (relative decreases of 10%, 20% and 30%), and physical inactivity (absolute decreases of 5%, 10% and 15%). Probabilistic sensitivity analyses were conducted. RESULTS: Under the conservative, intermediate and optimistic scenarios, we estimated 10.8% (95% CI: 7.3-14.0), 20.7% (95% CI: 15.6-25.2) and 29.1% (95% CI: 22.6-35.0) fewer CHD deaths in 2020. For the optimistic scenario, 15% absolute reductions in smoking could decrease CHD deaths by 8.9%-11.6%, Salt intake relative reductions of 30% by approximately 5.9-8.9%; 3% reductions in saturated fat intake by 6.3-7.5%, and 15% absolute increases in physical activity by 3.7 5.3%. CONCLUSIONS: Modest and feasible policy-based reductions in cardiovascular risk factors (already been achieved in some other countries) could translate into substantial reductions in future CHD deaths across Europe. However, this would require the European Union to more effectively implement powerful evidence-based prevention policies. PMID- 26812644 TI - Klebsiella pneumoniae Is Able to Trigger Epithelial-Mesenchymal Transition Process in Cultured Airway Epithelial Cells. AB - The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1alpha mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells. PMID- 26812646 TI - Financing Maternal Health and Family Planning: Are We on the Right Track? Evidence from the Reproductive Health Subaccounts in Mexico, 2003-2012. AB - OBJECTIVE: To analyze whether the changes observed in the level and distribution of resources for maternal health and family planning (MHFP) programs from 2003 to 2012 were consistent with the financial goals of the related policies. MATERIALS AND METHODS: A longitudinal descriptive analysis of the Mexican Reproductive Health Subaccounts 2003-2012 was performed by financing scheme and health function. Financing schemes included social security, government schemes, household out-of-pocket (OOP) payments, and private insurance plans. Functions were preventive care, including family planning, antenatal and puerperium health services, normal and cesarean deliveries, and treatment of complications. Changes in the financial imbalance indicators covered by MHFP policy were tracked: (a) public and OOP expenditures as percentages of total MHFP spending; (b) public expenditure per woman of reproductive age (WoRA, 15-49 years) by financing scheme; (c) public expenditure on treating complications as a percentage of preventive care; and (d) public expenditure on WoRA at state level. Statistical analyses of trends and distributions were performed. RESULTS: Public expenditure on government schemes grew by approximately 300%, and the financial imbalance between populations covered by social security and government schemes decreased. The financial burden on households declined, particularly among households without social security. Expenditure on preventive care grew by 16%, narrowing the financing gap between treatment of complications and preventive care. Finally, public expenditure per WoRA for government schemes nearly doubled at the state level, although considerable disparities persist. CONCLUSIONS: Changes in the level and distribution of MHFP funding from 2003 to 2012 were consistent with the relevant policy goals. However, improving efficiency requires further analysis to ascertain the impact of investments on health outcomes. This, in turn, will require better financial data systems as a precondition for improving the monitoring and accountability functions in Mexico. PMID- 26812647 TI - Reproducibility of Brain Morphometry from Short-Term Repeat Clinical MRI Examinations: A Retrospective Study. AB - PURPOSE: To assess the inter session reproducibility of automatic segmented MRI derived measures by FreeSurfer in a group of subjects with normal-appearing MR images. MATERIALS AND METHODS: After retrospectively reviewing a brain MRI database from our institute consisting of 14,758 adults, those subjects who had repeat scans and had no history of neurodegenerative disorders were selected for morphometry analysis using FreeSurfer. A total of 34 subjects were grouped by MRI scanner model. After automatic segmentation using FreeSurfer, label-wise comparison (involving area, thickness, and volume) was performed on all segmented results. An intraclass correlation coefficient was used to estimate the agreement between sessions. Wilcoxon signed rank test was used to assess the population mean rank differences across sessions. Mean-difference analysis was used to evaluate the difference intervals across scanners. Absolute percent difference was used to estimate the reproducibility errors across the MRI models. Kruskal Wallis test was used to determine the across-scanner effect. RESULTS: The agreement in segmentation results for area, volume, and thickness measurements of all segmented anatomical labels was generally higher in Signa Excite and Verio models when compared with Sonata and TrioTim models. There were significant rank differences found across sessions in some labels of different measures. Smaller difference intervals in global volume measurements were noted on images acquired by Signa Excite and Verio models. For some brain regions, significant MRI model effects were observed on certain segmentation results. CONCLUSIONS: Short-term scan-rescan reliability of automatic brain MRI morphometry is feasible in the clinical setting. However, since repeatability of software performance is contingent on the reproducibility of the scanner performance, the scanner performance must be calibrated before conducting such studies or before using such software for retrospective reviewing. PMID- 26812648 TI - Inaugurating the Everett Mendelsohn Prize. PMID- 26812649 TI - Distribution of Total Depressive Symptoms Scores and Each Depressive Symptom Item in a Sample of Japanese Employees. AB - BACKGROUND: In a previous study, we reported that the distribution of total depressive symptoms scores according to the Center for Epidemiologic Studies Depression Scale (CES-D) in a general population is stable throughout middle adulthood and follows an exponential pattern except for at the lowest end of the symptom score. Furthermore, the individual distributions of 16 negative symptom items of the CES-D exhibit a common mathematical pattern. To confirm the reproducibility of these findings, we investigated the distribution of total depressive symptoms scores and 16 negative symptom items in a sample of Japanese employees. METHODS: We analyzed 7624 employees aged 20-59 years who had participated in the Northern Japan Occupational Health Promotion Centers Collaboration Study for Mental Health. Depressive symptoms were assessed using the CES-D. The CES-D contains 20 items, each of which is scored in four grades: "rarely," "some," "much," and "most of the time." The descriptive statistics and frequency curves of the distributions were then compared according to age group. RESULTS: The distribution of total depressive symptoms scores appeared to be stable from 30-59 years. The right tail of the distribution for ages 30-59 years exhibited a linear pattern with a log-normal scale. The distributions of the 16 individual negative symptom items of the CES-D exhibited a common mathematical pattern which displayed different distributions with a boundary at "some." The distributions of the 16 negative symptom items from "some" to "most" followed a linear pattern with a log-normal scale. CONCLUSIONS: The distributions of the total depressive symptoms scores and individual negative symptom items in a Japanese occupational setting show the same patterns as those observed in a general population. These results show that the specific mathematical patterns of the distributions of total depressive symptoms scores and individual negative symptom items can be reproduced in an occupational population. PMID- 26812650 TI - Catastrophic medical expenditure risk. AB - We propose a measure of household exposure to particularly onerous medical expenses. The measure can be decomposed into the probability that medical expenditure exceeds a threshold, the loss due to predictably low consumption of other goods if it does and the further loss arising from the volatility of medical expenses above the threshold. Depending on the choice of threshold, the measure is consistent with a model of reference-dependent utility with loss aversion. Unlike the risk premium, the measure is only sensitive to particularly high expenses, and can identify households that expect to incur such expenses and would benefit from subsidised, but not actuarially fair, insurance. An empirical illustration using data from seven Asian countries demonstrates the importance of taking account of informal insurance and reveals clear differences in catastrophic medical expenditure risk across and within countries. In general, risk is higher among poorer, rural and chronically ill populations. PMID- 26812651 TI - Meiotic Recombination in Neurospora crassa Proceeds by Two Pathways with Extensive Holliday Junction Migration. AB - Analysis of thousands of Deltamsh-2 octads using our fluorescent recombination system indicates that, as in other filamentous fungi, symmetric heteroduplex is common in the his-3 region of Neurospora crassa. Symmetric heteroduplex arises from Holliday junction migration, and we suggest this mechanism explains the high frequency of His+ spores in heteroallelic crosses in which recombination is initiated cis to the his-3 allele further from the initiator, cog+. In contrast, when recombination is initiated cis to the his-3 allele closer to cog+, His+ spores are mainly a result of synthesis-dependent strand annealing, yielding asymmetric heteroduplex. Loss of Msh-2 function increases measures of allelic recombination in both his-3 and the fluorescent marker gene, indicating that mismatches in asymmetric heteroduplex, as in Saccharomyces cerevisiae, tend to be repaired in the direction of restoration. Furthermore, the presence of substantial numbers of conversion octads in crosses lacking Msh-2 function suggests that the disjunction pathway described in S. cerevisiae is also active in Neurospora, adding to evidence for a universal model for meiotic recombination. PMID- 26812652 TI - Heart Rate Variability Is Associated with Exercise Capacity in Patients with Cardiac Syndrome X. AB - Heart rate variability (HRV) reflects the healthiness of autonomic nervous system, which is associated with exercise capacity. We therefore investigated whether HRV could predict the exercise capacity in the adults with cardiac syndrome X (CSX). A total of 238 subjects (57+/-12 years, 67.8% men), who were diagnosed as CSX by the positive exercise stress test and nearly normal coronary angiogram were enrolled. Power spectrum from the 24-hour recording of heart rate was analyzed in frequency domain using total power (TP) and spectral components of the very low frequency (VLF), low frequency (LF) and high frequency (HF) ranges. Among the study population, 129 subjects with impaired exercise capacity during the treadmill test had significantly lower HRV indices than those with preserved exercise capacity (>=90% of the age predicted maximal heart rate). After accounting for age, sex, and baseline SBP and heart rate, VLF (odds ratio per 1SD and 95% CI: 2.02, 1.19-3.42), LF (1.67, 1.10-2.55), and TP (1.82, 1.17 2.83) remained significantly associated with preserved exercise capacity. In addition, increased HRV indices were also associated with increased exercise duration, rate-pressure product, and heart rate recovery, independent of age, body mass index, and baseline SBP and heart rate. In subgroup analysis, HRV indices demonstrated similar predictive values related to exercise capacity across various subpopulations, especially in the young. In patients with CSX, HRV was independently associated with exercise capacity, especially in young subjects. The healthiness of autonomic nervous system may have a role in modulating the exercise capacity in patients with CSX. PMID- 26812654 TI - Biodistribution and Pharmacokinetics Study of siRNA-loaded Anti-NTSR1-mAb functionalized Novel Hybrid Nanoparticles in a Metastatic Orthotopic Murine Lung Cancer Model. AB - Small interfering RNA (siRNA) is effective in silencing critical molecular pathways in cancer. The use of this tool as a treatment modality is limited by lack of an intelligent carrier system to enhance the preferential delivery of this molecule to specific targets in vivo. In the present study, the in vivo behavior of novel anti-NTSR1-mAb-functionalized antimutant K-ras siRNA-loaded hybrid nanoparticles, delivered by i.p. injection to non-small-cell lung cancer in mice models, was investigated and compared to that of a naked siRNA formulation. The siRNA in anti-NTSR1-mAb-functionalized hybrid nanoparticles was preferentially accumulated in tumor-bearing lungs and metastasized tumor for at least 48 hours while the naked siRNA formulation showed lack of preferential accumulation in all of the organs monitored. The plasma terminal half-life of nanoparticle-delivered siRNA was 11 times higher (17-1.5 hours) than that of the naked siRNA formulation. The mean residence time and AUClast were 3.4 and 33 times higher than the corresponding naked siRNA formulation, respectively. High performance liquid chromatography analysis showed that the hybrid nanoparticle carrier system protected the encapsulated siRNA against degradation in vivo. Our novel anti-NTSR1-mAb-functionalized hybrid nanoparticles provide a useful platform for in vivo targeting of siRNA for both experimental and clinical purposes. PMID- 26812653 TI - Silencing CCR2 in Macrophages Alleviates Adipose Tissue Inflammation and the Associated Metabolic Syndrome in Dietary Obese Mice. AB - Adipose tissue macrophage (ATM)-mediated inflammation is a key feature contributing to the adverse metabolic outcomes of dietary obesity. Recruitment of macrophages to obese adipose tissues (AT) can occur through the engagement of CCR2, the receptor for MCP-1 (monocyte chemoattractant protein-1), which is expressed on peripheral monocytes/macrophages. Here, we show that i.p. administration of a rabies virus glycoprotein-derived acetylcholine receptor binding peptide effectively delivers complexed siRNA into peritoneal macrophages and ATMs in a mouse model of high-fat diet-induced obesity. Treatment with siRNA against CCR2 inhibited macrophage infiltration and accumulation in AT and, therefore, proinflammatory cytokines produced by macrophages. Consequently, the treatment significantly improved glucose tolerance and insulin sensitivity profiles, and also alleviated the associated symptoms of hepatic steatosis and reduced hepatic triglyceride production. These results demonstrate that disruption of macrophage chemotaxis to the AT through cell-targeted gene knockdown strategies can provide a therapeutic intervention for obesity-related metabolic diseases. The study also highlights a siRNA delivery approach for targeting specific monocyte subsets that contribute to obesity-associated inflammation without affecting the function of other tissue-resident macrophages that are essential for host homeostasis and survival. PMID- 26812656 TI - Characterization of two novel alcohol short-chain dehydrogenases/reductases from Ralstonia eutropha H16 capable of stereoselective conversion of bulky substrates. AB - Biocatalysis has significant advantages over organic synthesis in the field of chiral molecule production and several types of stereoselective enzymes are already in use in industrial biotechnology. However, there is still a high demand for new enzymes capable of transforming bulky molecules with sufficient operability. In order to reveal novel high-potential biocatalysts, the complete genome of the beta-proteobacterium Ralstonia eutropha H16 was screened for potential short-chain dehydrogenases/reductases (SDRs). We were able to identify two (S)-enantioselective SDRs named A5 and B3. These showed clear preference towards long-chain and aromatic secondary alcohols, aldehydes and ketones, with diaryl diketone benzil as one of the best substrates. In addition the phylogenetic analysis of all enzyme types, which are known to facilitate benzil reduction, revealed at least two separate evolutionary clusters. Our results indicate the biotechnological potential of SDRs A5 and B3 for the production of chiral compounds with potential commercial value. PMID- 26812655 TI - Efficient Restoration of the Dystrophin Gene Reading Frame and Protein Structure in DMD Myoblasts Using the CinDel Method. AB - The CRISPR/Cas9 system is a great revolution in biology. This technology allows the modification of genes in vitro and in vivo in a wide variety of living organisms. In most Duchenne muscular dystrophy (DMD) patients, expression of dystrophin (DYS) protein is disrupted because exon deletions result in a frame shift. We present here the CRISPR-induced deletion (CinDel), a new promising genome-editing technology to correct the DMD gene. This strategy is based on the use of two gRNAs targeting specifically exons that precede and follow the patient deletion in the DMD gene. This pair of gRNAs induced a precise large additional deletion leading to fusion of the targeted exons. Using an adequate pair of gRNAs, the deletion of parts of these exons and the intron separating them restored the DMD reading frame in 62% of the hybrid exons in vitro in DMD myoblasts and in vivo in electroporated hDMD/mdx mice. Moreover, adequate pairs of gRNAs also restored the normal spectrin-like repeat of the dystrophin rod domain; such restoration is not obtained by exon skipping or deletion of complete exons. The expression of an internally deleted DYS protein was detected following the formation of myotubes by the unselected, treated DMD myoblasts. Given that CinDel induces permanent reparation of the DMD gene, this treatment would not have to be repeated as it is the case for exon skipping induced by oligonucleotides. PMID- 26812657 TI - Autotrophic hydrogen photoproduction by operation of carbon-concentrating mechanism in Chlamydomonas reinhardtii under sulfur deprivation condition. AB - Under autotrophic conditions, starch plays an important role in establishing anoxic conditions during PSII-dependent hydrogen (H2) photoproduction in microalgae. This is because starch is the sole organic substrate during respiratory consumption of internal oxygen (O2) from PSII-dependent direct pathway. Herein, we propose a novel approach to further facilitate the internal starch synthesis of Chlamydomonas reinhardtii through the operation of carbon concentrating mechanism (CCM) along with a two-stage process based on sulfur (S) deprivation, thereby resulting in enhanced anaerobic capacity during PSII dependent H2 photoproduction. When CCM-induced cells were exposed to high levels of carbon dioxide (CO2) (5%, v/v) with S deprivation, internal levels of starch were significantly elevated by retaining a functional CCM with the boosted photosynthetic activity during 24h of O2 evolution phase (I) of S deprivation. Consequently, during H2 production phase of S deprivation at irradiance of 50MUEm(-2)s(-1), the concentrations of starch and H2 in CCM-induced cells were remarkably enhanced by 65.0% and 218.9% compared to that of CCM-uninduced cells, respectively. The treatment of low-CO2-driven CCM induction prior to S deprivation is a cost-effective and energy-efficient strategy that significantly improves the solar-driven H2 production by microalgae; this is particularly realizable in an industrial scale. PMID- 26812658 TI - Near-freezing effects on the proteome of industrial yeast strains of Saccharomyces cerevisiae. AB - At near-freezing temperatures (0-4 degrees C), the growth of the yeast Saccharomyces cerevisiae stops or is severely limited, and viability decreases. Under these conditions, yeast cells trigger a biochemical response, in which trehalose and glycerol accumulate and protect them against severe cold and freeze injury. However, the mechanisms that allow yeast cells to sustain this response have been not clarified. The effects of severe cold on the proteome of S. cerevisiae have been not investigated and its importance in providing cell survival at near-freezing temperatures and upon freezing remains unknown. Here, we have compared the protein profile of two industrial baker's yeast strains at 30 degrees C and 4 degrees C. Overall, a total of 16 proteins involved in energy metabolism, translation and redox homeostasis were identified as showing increased abundance at 4 degrees C. The predominant presence of glycolytic proteins among those upregulated at 4 degrees C, likely represents a mechanism to maintain a constant supply of ATP for the synthesis of glycerol and other protective molecules. Accumulation of these molecules is by far the most important component in enhancing viability of baker's yeast strains upon freezing. Overexpression of genes encoding certain proteins associated with translation or redox homeostasis provided specifically protection against extreme cold damage, underlying the importance of these functions in the near-freezing response. PMID- 26812661 TI - From the Editor-in-Chief's Desk. PMID- 26812659 TI - Sleep reverts changes in human gray and white matter caused by wake-dependent training. AB - Learning leads to rapid microstructural changes in gray (GM) and white (WM) matter. Do these changes continue to accumulate if task training continues, and can they be reverted by sleep? We addressed these questions by combining structural and diffusion weighted MRI and high-density EEG in 16 subjects studied during the physiological sleep/wake cycle, after 12 h and 24 h of intense practice in two different tasks, and after post-training sleep. Compared to baseline wake, 12 h of training led to a decline in cortical mean diffusivity. The decrease became even more significant after 24 h of task practice combined with sleep deprivation. Prolonged practice also resulted in decreased ventricular volume and increased GM and WM subcortical volumes. All changes reverted after recovery sleep. Moreover, these structural alterations predicted cognitive performance at the individual level, suggesting that sleep's ability to counteract performance deficits is linked to its effects on the brain microstructure. The cellular mechanisms that account for the structural effects of sleep are unknown, but they may be linked to its role in promoting the production of cerebrospinal fluid and the decrease in synapse size and strength, as well as to its recently discovered ability to enhance the extracellular space and the clearance of brain metabolites. PMID- 26812660 TI - Antivirulence Isoquinolone Mannosides: Optimization of the Biaryl Aglycone for FimH Lectin Binding Affinity and Efficacy in the Treatment of Chronic UTI. AB - Uropathogenic E. coli (UPEC) employ the mannose-binding adhesin FimH to colonize the bladder epithelium during urinary tract infection (UTI). Previously reported FimH antagonists exhibit good potency and efficacy, but low bioavailability and a short half-life in vivo. In a rational design strategy, we obtained an X-ray structure of lead mannosides and then designed mannosides with improved drug-like properties. We show that cyclizing the carboxamide onto the biphenyl B-ring aglycone of biphenyl mannosides into a fused heterocyclic ring, generates new biaryl mannosides such as isoquinolone 22 (2-methyl-4-(1-oxo-1,2 dihydroisoquinolin-7-yl)phenyl alpha-d-mannopyranoside) with enhanced potency and in vivo efficacy resulting from increased oral bioavailability. N-Substitution of the isoquinolone aglycone with various functionalities produced a new potent subseries of FimH antagonists. All analogues of the subseries have higher FimH binding affinity than unsubstituted lead 22, as determined by thermal shift differential scanning fluorimetry assay. Mannosides with pyridyl substitution on the isoquinolone group inhibit bacteria-mediated hemagglutination and prevent biofilm formation by UPEC with single-digit nanomolar potency, which is unprecedented for any FimH antagonists or any other antivirulence compounds reported to date. PMID- 26812662 TI - Tough Talk: Discussing Fertility Preservation with Adolescents and Young Adults with Cancer. PMID- 26812663 TI - Matched Marrow, Sibling Shadow: The Epidemiology, Experience, and Ethics of Sibling Donors of Stem Cells. PMID- 26812664 TI - The Doctor-Patient Relationship in the Adolescent Cancer Setting: A Developmentally Focused Literature Review. AB - Several national reports and many individuals in the clinical oncology community have defined the adolescent and young adult (AYA) cancer population as individuals diagnosed between the ages of 15 and 39. However, neuroscience and developmental research have identified important decision-making skills (e.g., information processing, reasoning, emotion regulation) that are not fully developed during adolescence, making general, AYA-focused doctor-patient interaction guidelines potentially questionable for the adolescent cancer population. Most studies include adolescents in samples of pediatric cancer patients or include adolescents in samples of young adult cancer patients, but studies rarely consider adolescent cancer patients as a distinct, developmentally unique group. A systematic literature review was undertaken in October 2014 to begin to understand what is known about the doctor-patient relationship and communication preferences within adolescent oncology. From the 25 included studies, three important conclusions emerged: (1) discrepancies among adolescent patients, parents, and providers about the desired extent of involvement in treatment-related decisions; (2) patient desire for developmentally and culturally appropriate information provision; and (3) the desire and preference for how information is delivered, with recognition that these preferences may change with age. There was some variation in themes by study design, with studies directly observing medical consultations reporting less adolescent involvement in discussions than studies that surveyed doctors. The results of this review support the need for developmentally focused research and clinical guidelines that emphasize the experience of adolescent cancer patients separate from their older and younger counterparts. PMID- 26812665 TI - Exploration of Morbidity in a Serial Study of Long-Term Brain Tumor Survivors: A Focus on Pain. AB - PURPOSE: Children surviving brain tumors are frequently identified as having substantially decreased health-related quality of life (HRQL) in cross-sectional studies. This study explored the HRQL of a cohort of such survivors, who were recruited as adolescents and followed for a decade, in order to determine the trajectory of their morbidities. METHOD: Children diagnosed between January 1, 1985, and December 31, 1998, more than 2 years from diagnosis (N = 40), were recruited in 2000/2001 (T1) aged 16.74 +/- 4.23 years. Health Utilities Index questionnaires (HUI2/3) were completed in 2000/2001 and again at 5 years (T2) and 10 years (T3), with 37 and 25 participants then aged 21.54 +/- 4.29 and 27.97 +/- 4.07 years, respectively. In addition to study subjects, parental proxies completed questionnaires at T1 and T2, while study subjects selected proxies at T3. Single attributes (domains/dimensions) of HRQL and details of pain were analyzed. RESULTS: Cognition was the attribute compromised most often (T1 = 66.7% of participants, T2 = 62.2%, T3 = 60.0%). Pain was also reported frequently (T1 = 35%, T2 = 25%, T3 = 52%), and at T3 correlated moderately with HUI2 sensation (0.77) and HUI3 vision (0.44), speech (0.51), and ambulation (0.50). The lower median utility score for pain at T3 than at T1/T2 was a clinically important difference. Severe pain was identified in the lower extremities, back, upper extremities, and abdomen. Morbidity was observed also in emotion (worry HUI2 and unhappiness HUI3), sensation, and vision. CONCLUSION: Decreased HRQL in survivors of brain tumors in childhood is multifaceted. Pain is a prominent burden, along with morbidity in cognition, emotion, sensation, and vision. Further studies should explore pain and neurologic deficits, and potential opportunities for therapeutic intervention. PMID- 26812666 TI - Modeling interdependent animal movement in continuous time. AB - This article presents a new approach to modeling group animal movement in continuous time. The movement of a group of animals is modeled as a multivariate Ornstein Uhlenbeck diffusion process in a high-dimensional space. Each individual of the group is attracted to a leading point which is generally unobserved, and the movement of the leading point is also an Ornstein Uhlenbeck process attracted to an unknown attractor. The Ornstein Uhlenbeck bridge is applied to reconstruct the location of the leading point. All movement parameters are estimated using Markov chain Monte Carlo sampling, specifically a Metropolis Hastings algorithm. We apply the method to a small group of simultaneously tracked reindeer, Rangifer tarandus tarandus, showing that the method detects dependency in movement between individuals. PMID- 26812667 TI - Primary lumbar hernia: A rarely encountered hernia. AB - INTRODUCTION: Lumbar hernia is an uncommon abdominal wall hernia, making its diagnosis and management a challenge to the treating surgeon. Presentation may be misleading and diagnosis often missed. An imaging study forms an indispensable aid in the diagnosis and surgery is the only treatment option. PRESENTATION OF CASE: A 42 year old male presented with history of pain in lower back of 4 years duration and was being treated symptomatically over 4 years with analgesics and physiotherapy. He had noticed a swelling over the left side of his mid-back and consequently on examination was found to have a primary acquired lumbar hernia arising from the deep superior lumbar triangle of Grynfelt. Diagnosis was confirmed by Computed Tomographic imaging. DISCUSSION: A lumbar hernia may be primary or secondary with only about 300 cases of primary lumbar hernia reported in literature. Lumbar hernias manifest through two possible defects in the posterior abdominal wall, the superior being more common. Management remains surgical with various techniques emerging over the years. The patient at our center underwent an open sublay mesh repair with excellent outcome. CONCLUSION: A surgeon may encounter a primary lumbar hernia perhaps once in his lifetime making it an interesting surgical challenge. Sound anatomical knowledge and adequate imaging are indispensable. Inspite of advances in minimally invasive surgery, it cannot be universally applied to patients with lumbar hernia and management requires a more tailored approach. PMID- 26812669 TI - Retroperitoneal mass presenting as recurrent inguinal hernia: A case report. AB - INTRODUCTION: Retroperitoneal masses presenting as an inguinal hernia are rare conditions. PRESENTATION OF CASE: A 53 year old male admitted with the symptoms of weight loss, abdominal discomfort and left sided recurrent inguinal hernia. Physical examination demonstrated an abdominal mass in the left flank and an irreducible, painless scrotal mass. He had a history of left sided inguinal hernia surgery six years ago. Computed tomography revealed a large enhancing left sided retroperitoneal mass invading the colon, pancreas and kidney and it was going down towards the left scrotum. Unblock tumor resection including the neighboring organs (left kidney, left colon, distal pancreas with spleen) was performed. Scrotal extension of the tumor was also excised and the inguinal canal was repaired primarily. Histopathology of the mass was myxoid-liposarcoma. The patient has disease free, without hernia recurrence but poor in renal function after twenty months follow-up. DISCUSSION: Large retroperitoneal tumors may grow towards the inguinal region and they can mimic an inguinal hernia. An irreducible, painless and hard scrotal mass should be considered from this perspective. PMID- 26812668 TI - Atypical breasts cancers. AB - INTRODUCTION: With increasing incidence of breast cancers there are now a larger number of cases diagnosed with rare malignancies. These can be diagnostic dilemmas and management strategy can be different by various breast multi disciplinary teams (MDT). We aim to discuss the evidence-based approach for management of these atypical breast cancers which were identified in patients from a single breast screening unit. METHOD: Patient with unusual breast malignancies (all types except invasive ductal and lobular) treated under the care of a single surgeon were identified during the breast multi-disciplinary discussion from 2011 to 2015. The histology and management of these cases were reviewed and literature search of electronic databases via PubMed and the search engines Google/Google Scholar was performed. Emphasis on keywords based on the histology type was used to limit search. Search was focused on the diagnosis, management and prognosis of these unusual breast cancers. CONCLUSION: This series aims to focus on the evidence-based management of these rare breast malignancies; the diagnosis of which is crucial as it affects the overall treatment and prognosis. PMID- 26812670 TI - Two-stage surgical resection of an atypical teratoid rhabdoid tumor occupying the infratentorial and supratentorial compartment in children under two years: Report of two cases. AB - INTRODUCTION: Atypical teratoid rhabdoid tumors are highly malignant neoplasms that present in young children and can grow to a large size. Maximal safe surgical resection is a mainstay of treatment. PRESENTATION OF CASES: Two cases of children under the age of two with large tumors involving the supratentorial and infratentorial compartments are presented. A two-staged operative approach combining a standard suboccipital approach to the fourth ventricle followed by an infratentorial, supracerebellar approach was utilized for resection. DISCUSSION: Maximal safe surgical resection of large tumors in young children is challenging. A staged approach is presented that affords maximal tumor resection while minimizing perioperative morbidity. CONCLUSION: A staged operative approach appears safe and efficacious when resecting large tumors from both the infratentorial and supratentorial compartments in children less than two years of age. PMID- 26812671 TI - A tumoral mass (local recurrence of renal cell carcinoma) causing massive intraabdominal bleeding after blunt abdominal trauma. AB - BACKGROUND: Solid organ injury after abdominal trauma is a common condition, however, injury of the local recurrent tumoral masses following abdominal trauma is rare. The injuries and bleeding in recurrent tumors tend to be highly serious since they are more fragile. The bleedings caused by renal cell carcinomas and by the traumatic laceration of their recurrence commonly occur in the retroperitoneum. In this report, we present a 55-year-old female patient who underwent emergency surgery due to intraabdominal bleeding and bleeding was from the recurrence of a renal cell carcinomas. PRESENTATION OF CASE: The 55-year-old female patient was admitted to the emergency service with intraabdominal bleeding. Physical examination revealed tenderness in the right lower quadrant, particularly in the traumatic area. Ultrasonography and computed tomography revealed diffuse intraabdominal fluid and a ruptured bleeding mass was excised. Pathological analysis indicated that the mass was isolated local recurrence of renal cell carcinoma. DISCUSSION: Solid organ injury caused by blunt abdominal trauma may be accompanied by tumoral laceration; however, minor bleeding may occur in cases with blunt trauma, coexistence of blunt abdominal trauma with local recurrence and massive bleeding is extremely rare. Control of bleeding is more challenging in tumoral tissues compared to normal tissues. The bleeding intraabdominal area rather than the retroperitoneal area, and this condition was attributed to the peritoneal tear caused by the trauma. CONCLUSION: Local recurrent tumoral masses may be the source of the intraabdominal massive bleeding after blunt trauma. PMID- 26812672 TI - Higher-Order Structure-Of-Intellect Abilities. AB - Using data available from the published reports of factor analyses performed by the Aptitudes Research Project at the University of Southern California, investigations were made into the possibility of demonstrating higher-order factorial abilities latent in those data. Since the policy in those analyses had been to rotate axes orthogonally rather than obliquely, there was no direct information regarding intercorrelations among first-order or basic factors. By combining salient tests for each basic factor, and using their loadings on the obtained factors, correlations were estimated among representatives of those factors. Several methods were devised for factoranalyzing those intercorrelations, applying experimental controls that seemed to be needed, in view of the three-faceted nature of each basic ability. Evidence was found for a large number of second-order abilities and a smaller number of third-order factors, connected with many parts of the structure-of-intellect model, within the limits of available data. In general, the results provide excellent support for the model and for its oblique nature, and for relative discriminability of its categories. Implications for higher-order factorial procedures, for the testing of intelligence, for research, both bivariate and multivariate, and for general psychological theory are suggested. PMID- 26812673 TI - Canonical Correlation Analysis As A Special Case Of A Structural Relations Model. AB - Canonical correlation analysis is commonly considered to be a general model for most parametric bivariate and multivariate statistical methods. Because of its capability for handling multiple criteria and multiple predictors simultaneously, canonical correlation analysis has a great deal of appeal and has also enjoyed increasing application in the behavioral sciences. However, it has also been plagued by several serious shortcomings. In particular, researchers have been unable to determine the statistical significance of individual parameter estimates or to relax assumptions of the canonical model that are inconsistent with theory and/or observed data. As a result, canonical correlation analysis has found more application in exploratory research than in theory testing. This paper illustrates how these problems can be resolved by expressing canonical correlation as a special case of a linear structural relations model. PMID- 26812674 TI - Hierarchical Vs. Generally Overlapping Models In Psychiatric Classification. AB - This paper illustrates two formal models for psychiatric classification. The first model, called a hierarchical or tree structure, requires patient categories to be disjoint or strictly nested. The second model, called the generally overlapping or network model, allows patient categories to cut across each other in a variety of different ways. Thus, patient groups can be disjoint, strictly nested (as in a hierarchy), or partially overlapping. To derive classification schemes consistent with the structural models, two different clustering techniques were applied to interpatient similarity data collected on 50 psychiatric patients. A hierarchical clustering technique was applied to the similarity data to obtain a hierarchical classification. To obtain a generally overlapping classification, Peay's cliquing procedure was applied to the same data. Two criteria were used to compare the clustering solutions. First, a solution's goodness-of-fit to the original data was examined by calculating the proportion of variance accounted for by cluster categories. Second, the predictive accuracy of a solution was analyzed by looking at the categories' ability to predict treatment assignment. The generally overlapping solution produced the best fit to the original similarity data; however, the hierarchical solution's clusters tended to be more readily interpretable in terms of psychiatric syndromes. Both clustering solutions were relatively poor predictors of treatment assignment. It was concluded that the hierarchical and generally overlapping approaches, although not conclusively demonstrated, represented promising models for psychiatric classification. PMID- 26812675 TI - Corrections For Spurious Influences On Correlations Between Mmpi Scales. AB - Correlations between measures containing common elements have a spurious component due to the overlapping elements. For example, personality scales such as the MMPI and the CPI have subscales with overlapping items, so correlations between these subscales are spuriously influenced by this overlap. Methods for statistical and experimental adjustment of these spuriously influenced correlations are reviewed and compared, but are rejected in favor of Bashaw and Anderson's (1967) reliability solution. To illustrate the proposed correction and to show the potential magnitude of this spurious influence, the original "Minnesota normals" data on nine clinical subscales of the MMPI were analyzed. A comparison of the unadjusted and adjusted values showed that 32 of the 36 correlations were changed, six of them were radically changed, and in two cases the sign of the correlation was reversed. A principal components analysis was used to investigate changes in the correlation structure. PMID- 26812676 TI - Testing Main Effects Of Continuous Variables In Nonadditive Models. AB - Problems in testing main effects when there is interaction are discussed. A method by which main effects can be tested independently of the interaction is developed and compared with the hierarchical method. The hierarchical method is shown to be inadequate, as it does not provide sufficient control of the type I error rate. The alternative method provides control of the type I error rate, but is quite conservative. PMID- 26812677 TI - A Note On Specifying Parameter Values For Testing Covariance Matrix Hypotheses. AB - Eiting and Mellenbergh (1980) used Monte Carlo studies to investigate the power in testing covariance matrix hypotheses. Although their reasoning for specifying the common variance in the Monte Carlo study may have been incorrect, the results of a second Monte Carlo study appear to be realistic. It is recommended that simulations be based on empirical estimates of parameter values. PMID- 26812678 TI - Shape-Controlled Synthesis of Co2P Nanostructures and Their Application in Supercapacitors. AB - Co2P nanostructures with rod-like and flower-like morphologies have been synthesized by controlling the decomposition process of Co(acac)3 in oleylamine system with triphenylphosphine as phosphorus source. Investigations indicate that the final morphologies of the products are determined by their peculiar phosphating processes. Electrochemical measurements manifest that the Co2P nanostructures exhibit excellent morphology-dependent supercapacitor properties. Compared with that of 284 F g(-1) at a current density of 1 A g(-1) for Co2P nanorods, the capacitance for Co2P nanoflowers reaches 416 F g(-1) at the same current density. Furthermore, an optimized asymmetric supercapacitor by using Co2P nanoflowers as anode and graphene as cathode is fabricated. It can deliver a high energy density of 8.8 Wh kg(-1) (at a high power density of 6 kW kg(-1)) and good cycling stability with over 97% specific capacitance remained after 6000 cycles, which makes the Co2P nanostructures potential applications in energy storage/conversion systems. This study paves the way to explore a new class of cobalt phosphide-based materials for supercapacitor applications. PMID- 26812679 TI - Ethnobotany, phytochemistry, and pharmacology of the genus Litsea: An update. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The genus Litsea is one of the most diverse genera of evergreen trees or shrubs belong to Lauraceae, and comprises roughly 400 species of tree that are distributed abundantly throughout tropical and subtropical Asia, North and South America. Litsea species have been used globally in traditional medicine for the treatment of various diseases including influenza, stomach aches, diarrhea, diabetes, vomiting, bone pain, inflammation, illness related to the central nervous system and other ailments. The purpose of this review is to provide updated, comprehensive and categorized information on the ethnobotany, phytochemistry and pharmacological research of Litsea species in order to explore their therapeutic potential and evaluate future research opportunities. MATERIALS AND METHODS: All the available information on Litsea species was actualised by systematically searching the scientific literatures including Chinese, Korean, Japanese, Indian, and South American herbal classics, library catalogs and scientific databases (PubMed, SciFinder, Web of Science, Google Scholar, VIP and Wanfang). The Plant List, International Plant Name index and Scientific Database of China Plant Species were used to validate scientific names. RESULTS: 407 secondary metabolites have been reported from Litsea species. Litsea Species are sources of secondary metabolites with interesting chemical structures (alkaloids, lactones, sesquiterpenes, flavonoids, lignans, and essential oils) and significant bioactivities. Crude extracts, fractions and phytochemical constituents isolated from Litsea show a wide spectrum of in vitro and in vivo pharmacological activities including anticancer, anti-inflammatory, antimicrobial, antioxidant, antidiabetic, anti-HIV, insecticidal, etc. CONCLUSIONS: From data collected in this review, the genus Litsea comprises a wide range of therapeutically promising and valuable plants, and has attracted much attention owing to its multiple functions. Many traditional uses of Litsea species have now been validated by modern pharmacology research. Deep and systematic phytochemical investigation of the genus Litsea and the pharmacological properties, especially its mechanism of action and toxicology, to illustrate its ethnomedicinal use, explore the therapeutic potential and support further health-care product development will undoubtedly be the focus of further research. Therefore, detailed and extensive studies and clinical evaluation of Litsea species should be carried out in future for the safety approval of therapeutic applications. PMID- 26812680 TI - Antithrombocytopenic activity of carpaine and alkaloidal extract of Carica papaya Linn. leaves in busulfan induced thrombocytopenic Wistar rats. AB - ETHNOPHARMACOLOGICAL RELAVANCE: The decoction of Carica papaya Linn. leaves is used in folklore medicine in certain parts of Malaysia and Indonesia for the treatment of different types of thrombocytopenia associated with diseases and drugs. There are several scientific studies carried out on humans and animal models to confirm the efficacy of decoction of papaya leave for the treatment of disease induced and drug induced thrombocytopenia, however very little is known about the bio-active compounds responsible for the observed activity. The aim of present study was to identify the active phytochemical component of Carica papaya Linn. leaves decoction responsible for anti-thrombocytopenic activity in busulfan induced thrombocytopenic rats. MATERIALS AND METHODS: Antithrombocytopenic activity was assessed on busulfan induced thrombocytopenic Wistar rats. The antithrombocytopenic activity of different bio-guided fractions was evaluated by monitoring blood platelet count. Bioactive compound carpaine was isolated and purified by chromatographic methods and confirmed by spectroscopic methods (LC-MS and 1D/2D-1H/13C NMR) and the structure was confirmed by single crystal X-ray diffraction. Quantification of carpaine was carried out by LC-MS/MS equipped with XTerra((r)) MS C18 column and ESI-MS detector using 90:10 CH3CN:CH3COONH4 (6mM) under isocratic conditions and detected with multiple reaction monitoring (MRM) in positive ion mode. RESULTS: Two different phytochemical groups were isolated from decoction of Carica papaya leaves: phenolics, and alkaloids. Out of these, only alkaloid fraction showed good biological activity. Carpaine was isolated from the alkaloid fraction and exhibited potent activity in sustaining platelet counts upto 555.50+/-85.17*10(9)/L with no acute toxicity. CONCLUSIONS: This study scientifically validates the popular usage of decoction of Carica papaya leaves and it also proves that alkaloids particularly carpaine present in the leaves to be responsible for the antithrombocytopenic activity. PMID- 26812681 TI - Aberrant Circulating Th17 Cells in Patients with B-Cell Non-Hodgkin's Lymphoma. AB - Non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of neoplasm in which 90% are B-cell lymphomas and 10% T-cell lymphomas. Although T-helper 17 (Th17) cells have been implicated to be essential in the pathogenesis of autoimmune and inflammatory diseases, its role in B-cell non-Hodgkin's lymphoma (B-NHL) remains unknown. In this study, we observed a significantly decreased frequency of Th17 cells in peripheral blood from B-NHL patients compared with healthy individuals, accompanied with increased Th1 cells. IL-17AF plasma levels were remarkably decreased in B-NHL patients, accompanied with undetectable IL-17FF and unchangeable IL-17AA. Moreover, Th17 and Th1 cells became normalized after one or two cycles of chemotherapy. Interestingly, in B-NHL, circulating Th17 cells frequencies were significantly higher in relapsed patients than those in untreated patients or normal individuals. Meanwhile, there was no statistical difference regarding the frequencies of Th1 cells between relapsed and untreated patients. Taken these data together, circulating Th17 subset immune response may be associated with the response of patients to treatment and with different stages of disease. PMID- 26812683 TI - A Submersible, Off-Axis Holographic Microscope for Detection of Microbial Motility and Morphology in Aqueous and Icy Environments. AB - Sea ice is an analog environment for several of astrobiology's near-term targets: Mars, Europa, Enceladus, and perhaps other Jovian or Saturnian moons. Microorganisms, both eukaryotic and prokaryotic, remain active within brine channels inside the ice, making it unnecessary to penetrate through to liquid water below in order to detect life. We have developed a submersible digital holographic microscope (DHM) that is capable of resolving individual bacterial cells, and demonstrated its utility for immediately imaging samples taken directly from sea ice at several locations near Nuuk, Greenland. In all samples, the appearance and motility of eukaryotes were conclusive signs of life. The appearance of prokaryotic cells alone was not sufficient to confirm life, but when prokaryotic motility occurred, it was rapid and conclusive. Warming the samples to above-freezing temperatures or supplementing with serine increased the number of motile cells and the speed of motility; supplementing with serine also stimulated chemotaxis. These results show that DHM is a useful technique for detection of active organisms in extreme environments, and that motility may be used as a biosignature in the liquid brines that persist in ice. These findings have important implications for the design of missions to icy environments and suggest ways in which DHM imaging may be integrated with chemical life-detection suites in order to create more conclusive life detection packages. PMID- 26812685 TI - Efficiency of Health Care Production in Low-Resource Settings: A Monte-Carlo Simulation to Compare the Performance of Data Envelopment Analysis, Stochastic Distance Functions, and an Ensemble Model. AB - Low-resource countries can greatly benefit from even small increases in efficiency of health service provision, supporting a strong case to measure and pursue efficiency improvement in low- and middle-income countries (LMICs). However, the knowledge base concerning efficiency measurement remains scarce for these contexts. This study shows that current estimation approaches may not be well suited to measure technical efficiency in LMICs and offers an alternative approach for efficiency measurement in these settings. We developed a simulation environment which reproduces the characteristics of health service production in LMICs, and evaluated the performance of Data Envelopment Analysis (DEA) and Stochastic Distance Function (SDF) for assessing efficiency. We found that an ensemble approach (ENS) combining efficiency estimates from a restricted version of DEA (rDEA) and restricted SDF (rSDF) is the preferable method across a range of scenarios. This is the first study to analyze efficiency measurement in a simulation setting for LMICs. Our findings aim to heighten the validity and reliability of efficiency analyses in LMICs, and thus inform policy dialogues about improving the efficiency of health service production in these settings. PMID- 26812684 TI - Challenges in the Detection of Working Memory and Attention Decrements among Overweight Adolescent Girls. AB - BACKGROUND: The present study is unique in employing unusually difficult attention and working memory tasks to reveal subtle cognitive decrements among overweight/obese adolescents. It evaluated novel measures of background electroencephalographic (EEG) activity during one of the tasks and tested correlations of these and other measures with psychological and psychiatric predictors of obesity maintenance or progression. METHODS: Working memory and sustained attention tasks were presented to 158 female adolescents who were rated on dichotomous (body mass index percentile <85 vs. >=85) and continuous (triceps skinfold thickness) measures of adiposity. RESULTS: The results revealed a significant association between excess adiposity and performance errors during the working memory task. During the sustained attention task, overweight/obese adolescents exhibited more EEG frontal beta power as well as greater intraindividual variability in reaction time and beta power across task periods than their normal-weight peers. Secondary analyses showed that frontal beta power during the sustained attention task was positively correlated with anxiety, panic, borderline personality features, drug abuse, and loss of control over food intake. CONCLUSIONS: The findings suggest that working memory and sustained attention decrements do exist among overweight/obese adolescent girls. The reliable detection of the decrements may depend on the difficulty of the tasks as well as the manner in which performance and brain activity are measured. Future studies should examine the relevance of these decrements to dietary education efforts and treatment response. PMID- 26812682 TI - Co- and Post-Treatment with Lysine Protects Primary Fish Enterocytes against Cu Induced Oxidative Damage. AB - The aim of the work was primarily to explore the protective activity pathways of lysine against oxidative damage in fish in vivo and in enterocytes in vitro. First, grass carp were fed diets containing six graded levels of lysine (7.1-19.6 g kg-1 diet) for 56 days. Second, the enterocytes were treated with different concentrations of lysine (0-300 mg/L in media) prior to (pre-treatment), along with (co-treatment) or following (post-treatment) with 6 mg/L of Cu for 24 h. The results indicated that lysine improved grass carp growth performance. Meanwhile, lysine ameliorated lipid and protein oxidation by elevating the gene expression and activity of antioxidant enzymes (superoxide dismutase (SOD), glutathioneperoxidase (GPx), glutathione-S-transferase (GST) and reductase (GR)), and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA levels in fish intestine. The in vitro studies showed that co- and post-treatment with lysine conferred significant protection against Cu-induced oxidative damage in fish primary enterocytes as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) OD values, along with alkaline phosphatase (ALP) and lactate dehydrogenase activities, and the depletion of protein carbonyl (PC), malondialdehyde (MDA) and 8-hydroxydeoxyguanosine contents. Moreover, lysine co-treatment decreased the activities and mRNA level of cellular SOD, GPx, GST and GR compared with the Cu-only exposed group. Gene expression of the signalling molecule Nrf2 showed the same pattern as that of SOD activity, whereas Kelch-like ECH-associated protein 1b (Keap1b) followed the opposite trend, indicating that co-treatment with lysine induced antioxidant enzymes that protected against oxidative stress through Nrf2 pathway. In addition, post treatment with lysine increased proteasomal activity and blocked the Cu stimulated increase in mRNA levels of GST and associated catalase (CAT) and GST activities (P<0.01 and P<0.001). GR activity and gene expression, and glutathione (GSH) content followed an opposite trend to GST activity (P<0.05). Thus, post treatment of lysine elevated protein and DNA repair abilities and ameliorated the cellular redox state of enterocytes. The overall results suggest that lysine plays a significant role in the protection of fish intestine in vivo and in vitro through the induction of key antioxidant protection. PMID- 26812686 TI - Fast Electromagnetic Analysis of MRI Transmit RF Coils Based on Accelerated Integral Equation Methods. AB - A fast frequency domain full-wave electromagnetic simulation method is introduced for the analysis of MRI coils loaded with the realistic human body models. The approach is based on integral equation methods decomposed into two domains: 1) the RF coil array and shield, and 2) the human body region where the load is placed. The analysis of multiple coil designs is accelerated by introducing the precomputed magnetic resonance Green functions (MRGFs), which describe how the particular body model used responds to the incident fields from external sources. These MRGFs, which are precomputed once for a given body model, can be combined with any integral equation solver and reused for the analysis of many coil designs. This approach provides a fast, yet comprehensive, analysis of coil designs, including the port S-parameters and the electromagnetic field distribution within the inhomogeneous body. The method solves the full-wave electromagnetic problem for a head array in few minutes, achieving a speed up of over 150 folds with root mean square errors in the electromagnetic field maps smaller than 0.4% when compared to the unaccelerated integral equation-based solver. This enables the characterization of a large number of RF coil designs in a reasonable time, which is a first step toward an automatic optimization of multiple parameters in the design of transmit arrays, as illustrated in this paper, but also receive arrays. PMID- 26812687 TI - Correction: Comparing Effects of Biologic Agents in Treating Patients with Rheumatoid Arthritis: A Multiple Treatment Comparison Regression Analysis. PMID- 26812688 TI - The Relationship of Insulin-Like Growth Factor 2 to Fetal Growth and Adiposity. AB - Insulin-like growth factor 2 (IGF-2) is necessary for adequate human growth. Overexpression of the IGF2 gene is associated with fetal overgrowth and may play a role in the intrauterine programming of adipose tissue. As obesity in children is a major public health problem associated with early onset of comorbid metabolic diseases, identifying early life markers of obesity may serve as useful tool for counseling and implementation of preventive efforts before obesity develops. The relationship between IGF-2 and body composition is an emerging field of study and existing data are conflicting. In this review, we discuss the IGF2 gene and its function, highlight the proposed mechanisms for the effects of IGF-2 on adiposity, and examine the current literature studying the relationships between IGF-2 levels, changes within the IGF2 gene, weight, and adiposity. With additional study, IGF-2 may emerge as a useful marker of future obesity risk in infants. PMID- 26812689 TI - Diagnostic Accuracy of NT-ProBNP for Heart Failure with Sepsis in Patients Younger than 18 Years. AB - This clinical study investigated plasma NT-proBNP levels as a potential predictor of heart failure in pediatric patients with sepsis. Plasma NT-ProBNP levels of 211 pediatric patients with sepsis and 126 healthy children were measured. Patients were stratified as with heart failure (HF) or without heart failure (non HF). Patients were graded as having sepsis, severe sepsis, or septic shock. The optimal cut-off values of plasma NT-ProBNP for heart failure were determined by analyzing the receiver operating characteristic (ROC). In the HF, non-HF and control groups, the median plasma NT-proBNP levels were 3640, 656, and 226 ng/L, respectively. For all patients with sepsis, the optimal diagnostic cut-off value was 1268 ng/L for differentiating heart failure. In the severe sepsis patients and septic shock patients, the optimal diagnostic cut-off values were 1368 ng/L and 1525 ng/L, respectively. This report is the first one to reveal that NT proBNP may predict heart failure in children with sepsis. It provides an important clinical reference for the diagnosis of heart failure in pediatric patients with sepsis, and enables monitoring septic children for cardiac involvement. PMID- 26812690 TI - Salivary Cortisone Reflects Cortisol Exposure Under Physiological Conditions and After Hydrocortisone. AB - In this study we tested the use of salivary cortisol and cortisone as alternatives to serum cortisol. Salivary cortisol is often undetectable and contaminated by hydrocortisone. Salivary cortisone strongly reflects serum cortisol. PMID- 26812692 TI - Pareidolia in Neuroendocrinology: A Pituitary Macroadenoma Resembling "Big Bird". AB - The MRI picture of a pituitary macroadenoma with supra- and perisellar expansion resembled a famous character from a children's television series demonstrating that pareidolia is also observed in neuro-endocrinology and -radiology. PMID- 26812691 TI - Physical Activity and the Risk of Primary Hyperparathyroidism. AB - CONTEXT: Primary hyperparathyroidism (P-HPTH) is relatively common and predominantly affects women. Prior studies have shown that physical activity (PA) can lower PTH levels. OBJECTIVE: Our objective was to evaluate the hypothesis that lower PA is a risk factor for developing P-HPTH. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included 69 621 female participants in the Nurses' Health Study I followed for 22 years. EXPOSURES: PA and other dietary and demographic exposures were quantified via detailed, and validated, biennial questionnaires. OUTCOMES: Incident P-HPTH was confirmed by medical record review after initial assessment by questionnaire. Adjusted Cox proportional hazards models were used to evaluate whether PA was an independent risk factor for developing P-HPTH. We also evaluated the risk of developing P HPTH when combining low PA (<16 metabolic equivalent hours/week) with a previously identified independent risk factor for developing P-HPTH: low calcium intake (<800 mg/day). The relation between PA and PTH levels was evaluated in 625 participants. RESULTS: We confirmed 302 incident cases of P-HPTH during 1 474 993 person-years of follow-up. Participants in the highest quintile (Q) of PA had a 50% lower risk of developing P-HPTH: age-adjusted relative risks and 95% confidence intervals for incident P-HPTH by lowest to highest of PA were Q1 = 1.0 (reference); Q2 = 0.83 (0.60-1.15); Q3 = 0.84 (0.61-1.15); Q4 = 0.50 (0.34-0.74); Q5 = 0.50 (0.35-0.73); P for trend <.001. Extensive multivariable adjustments did not materially change these findings. The adjusted relative risk for developing P HPTH among participants with the combination lower PA and lower calcium intake was 2.37-fold (1.60-3.51) higher than in participants with higher PA and higher calcium intake. PA was inversely correlated with serum PTH (rho = -0.09, P = .03); the mean adjusted serum PTH in Q 2-5 of PA was lower than in Q 1 (36.3 vs 39.1 pg/mL, P = .02). CONCLUSION: Low physical activity may be a modifiable risk factor for developing P-HPTH in women. PMID- 26812693 TI - Elevated serum microRNA-122/222 levels are potential diagnostic biomarkers in Egyptian patients with chronic hepatitis C but not hepatic cancer. AB - MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that regulate gene expression at the post-transcriptional level. Because of their size, specificity, and relative stability in plasma, miRNAs can be used as diagnostic and prognostic biomarkers to monitor liver injury, such as that caused by hepatitis C virus (HCV) and liver cancer. In this study, we investigated miRNA expression patterns from the serum of Egyptian patients with HCV and liver cancer compared with matched healthy controls. Using microarray-based expression profiling followed by real-time quantitative polymerase chain reaction validation, we compared the levels of circulating miRNA-122 and miRNA-222 in serum from patients with hepatitis C virus (n = 40) and liver cancer (n = 60) to matched healthy controls (n = 30). MiRNA SNORD68 was the housekeeping endogenous control. We found that the serum levels of miR-122 and miR-222 were significantly elevated in HCV patients, but not in liver cancer patients, compared with controls. Receiver operating characteristic analysis revealed that miR-122 and miR-222 have a high diagnostic potential in discriminating patients with HCV from controls. Serum miR-222 was significantly higher in HCV patients compared to liver cancer patients. Our results indicate that serum miR-122 and miR-222 are elevated in Egyptian patients with chronic HCV, and these miRNAs have a strong potential to serve as novel biomarkers for liver injury but not specifically for liver cancer. PMID- 26812696 TI - A PSYCHOPHYSICAL APPROACH TO THE STUDY OF PERSONALITY TRAITS. AB - A total of 366 school children were rated by 12 teachers in respect of 11 personality traits. In a laboratory experiment, a group of 10 teachers estimated the degree of perceived similarity between the same traits. In a second laboratory experiment, estimates were obtained of the frequency with which the traits occur together. It was found that similarity of traits was proportional to the squared coefficient of inter-trait ccmelation. A similar relation was demonstrated for estimated co-frequency and inter-trait corre- lation. Furthermore, factor analyses of the three sets of data revealed essentially the same three factors of Intelligence, Sociability and Dependability. The results are discussed within a psychophysical framework regarding the subjects rated and traits estimated as stimuli in a person-perception experiment. PMID- 26812695 TI - Global rank tests for multiple, possibly censored, outcomes. AB - Clinical trials often collect multiple outcomes on each patient, as the treatment may be expected to affect the patient on many dimensions. For example, a treatment for a neurological disease such as ALS is intended to impact several dimensions of neurological function as well as survival. The assessment of treatment on the basis of multiple outcomes is challenging, both in terms of selecting a test and interpreting the results. Several global tests have been proposed, and we provide a general approach to selecting and executing a global test. The tests require minimal parametric assumptions, are flexible about weighting of the various outcomes, and are appropriate even when some or all of the outcomes are censored. The test we propose is based on a simple scoring mechanism applied to each pair of subjects for each endpoint. The pairwise scores are then reduced to a summary score, and a rank-sum test is applied to the summary scores. This can be seen as a generalization of previously proposed nonparametric global tests (e.g., O'Brien, 1984). We discuss the choice of optimal weighting schemes based on power and relative importance of the outcomes. As the optimal weights are generally unknown in practice, we also propose an adaptive weighting scheme and evaluate its performance in simulations. We apply the methods to analyze the impact of a treatment on neurological function and death in an ALS trial. PMID- 26812694 TI - Expression and mechanisms of long non-coding RNA genes MEG3 and ANRIL in gallbladder cancer. AB - The objective of this study was to investigate the expression, proliferation, and apoptosis function of long-chain non-coding RNA maternally expressed gene 3 (MEG3) and antisense non-coding RNA at the INK4 locus (ANRIL) in gallbladder cancer (GBC) tissues. GBC tissues and adjacent normal samples were collected from 84 patients from January 2008 to June 2010. Empty vector, pcDNA-MEG3, and pcDNA ANRIL vectors were transfected into GBC-SD and QBC939 cells. An MTT assay, real time quantitative polymerase chain reaction (RT-qPCR), flow cytometry, Western blotting, and immunohistochemistry were applied. The effects of MEG3 and ANRIL were also verified in mice. Compared with normal tissues, the expression of MEG3 was significantly lower in GBC tissues, whereas the expression of ANRIL was significantly higher (both P < 0.05). The overexpression of MEG3 and underexpression of ANRIL were significantly associated with GBC prognosis (both P < 0.05). The expressions of MEG3 and ANRIL were higher in pcDNA-MEG3 and pcDNA ANRIL-transfected cells than in empty vector-transfected cells in vitro (both P < 0.05). Most of the pcDNA-MEG3-transfected cells were in the G0-G1 phase, which showed reduced cell activity and clone counts and increased p53 and decreased cyclin D1, whereas the pcDNA-ANRIL-transfected cells were mostly in the S phase and showed contrasting behavior. Mice injected with pcDNA-MEG3-transfected cells had smaller and lighter tumors, decreased ki-67 levels, and increased caspase 3 levels, whereas those injected with pcDNA-ANRIL showed contrasting results (all P < 0.05). MEG3 can inhibit the proliferation of GBC cells and promote apoptosis, whereas ANRIL can improve the proliferation of gallbladder cells and inhibit apoptosis. Collectively, our results suggest that therapeutic strategies directed toward upregulating MEG3 and downregulating ANRIL may be clinically relevant for the inhibition of GBC deterioration. PMID- 26812697 TI - THE PATTERNS OF DYADIC FOREIGN CONFLICT FOR 1963. AB - Five patterns of dyadic foreign conflict behavior were delineated for 1963. The first of these patterns was negative communications, which accounted for patterns, violence intensity, and warning and defensive acts, marked the general decrease in military activity from 1966 to 1963. The most militant conflict behavior in 1963 was that of China to Taiwan and Taiwan to China. There were a number of warning and defensive acts, most noteworthy being those of Indonesia to Malaysia and Malaysia to Indonesia. Negative sanctions and unofficial incidence of violence were the most stable patterns of foreign conflict behavior between 1966 to 1963, each accounting for about ten percent of foreign conflict behavior. The United States was involved in a number of sanctions directed against Cuba, the Dominican Republic, Russia, and South Vietnam. The unofficial incidents of violence occurred most frequently in the less developed, smaller nations, and were frequently directed against major world powers. The negative communication pattern characterized the primary behavior of the major world powers. PMID- 26812698 TI - ADJECTIVE RATING SCALES FOR SELF DESCRIPTION. AB - Factor analysis of Gough's 300-item Adjective Check List identified 8 highest loading items for 7 factors of self-perception. These were alphabetized and presented with 6-point scales to 713 females in teacher training. Factor analysis of the 66 self-rating items replicated the original structure, and simple scale sums showed satisfactory internal consistency and test-retest stability. Correlations with another self-description inventory evidenced concurrent validity of the instrument, which should be valuable for rapid, straight-forward, quantified self-description. PMID- 26812699 TI - MULTIVARIATE ANALYSIS OF GANG DELINQUENCY: II. STRUCTURAL AND DYNAMIC PROPERTIES OF GANGS. AB - Measures of structural and dynamic properties of gangs are developed: size, differentiation, primary pattern strength, competing pattern strength, and territorial dispersion; and cohesiveness, uniformity of attitude, and felt effectiveness. Except for size and dispersion, all measures are derived from applications of cluster and factor analysis. Evidence of construct validity is provided. The measurements are then related to mean scores on five factors of behavior for sixteen gangs. It is found that less differentiated gangs engage in more property offenses; gangs with stronger primary pattern engage in more conflict and stable sex behaviors; gangs with greater cohesion engage in less property offenses and conflict behaviors. Discussion centers upon a distinction between behavioral and attitudinal cohesiveness. PMID- 26812701 TI - PATTERN CLUSTERING BY MULTIVARIATE MIXTURE ANALYSIS. AB - Cluster analysis is reformulated as a problem of estimating the para- meters of a mixture of multivariate distributions. The maximum-likelihood theory and numerical solution techniques are developed for a fairly general class of distributions. The theory is applied to mixtures of multivariate nor- mals (NORMIX) and mixtures of multivariate Bernoulli distributions (Latent Classes). The feasibility of the procedures is demonstrated by two examples of computer solutions for normal mixture models of the Fisher Iris data and of artifjcially generated clusters with unequal covariance matrices. PMID- 26812700 TI - SOCIAL DESIRABILITY AND THE TSC SCALES: A REPLICATION AND REPLY TO STEIN. AB - A replication of a study by Edwards, Klockars, and Abbott, 1970, using Tryon's sample, showed that each of the seven TSC scales had its highest loading on the first principal component. The results are in agreement with those obtained with a college sample. PMID- 26812702 TI - EXTENSIONS OF A MULTITRAIT-MULTIMETHOD MODEL TO EXPERIMENTAL PSYCHOLOGY. AB - A simplified description of restricted maximum likelihood factor analysis of multitrait-multimethod data is presented. The series of hypothetical exam- ples and data are taken from motivational-experimental psychology. Implications of the model and the relations between this approach and other multitrait-multimethod analytic techniques are discussed briefly. PMID- 26812703 TI - BRIEF REPORT: THE EFFECT OF AGGREGATION ON NONMETRIC MULTIDIMENSIONAL SCALING SOLUTIONS. AB - J A nonmetric multidimensional scaling analysis was done on similarities between 12 objects on data gathered from 42 subjects. First, each subject's data were used to produce a separate configuration. Then, data were aggregated over all subjects land a single solution Configuration was abtained. Comparisons between the tWO approaches were made. Generally, it was found that aggregation did not produce a configuration which differed greatly from those obtained by analyzing each subjeot's codiguration separately. However, the aggregate stress figures consistently indicated a far better fit than did the corresponding individual stress values. PMID- 26812704 TI - MEETING THE GOALS OF RESEARCH WITH MULTIPLE LINEAR REGRESSION. AB - Multiple linear regression is discussed as it relates to several goals of research: Predictability, Parsimony, Replication, and Validity Generalization. law. The emphasis i s upon the per cent of variance accounted for in the criterion under investigation, rather than on statistical significance from random events. Additional remarks concerning curvilinear relationships and data snooping are also presented. Dingman's Canons of Repmducibility are discussed within the framework of multiple linear regression and the goals of research. I These goals are presented with the development of a well established physical. PMID- 26812705 TI - Spatio-Temporal Multiscale Denoising of Fluoroscopic Sequence. AB - In the past 20 years, a wide range of complex fluoroscopically guided procedures have shown considerable growth. Biologic effects of the exposure (radiation induced burn, cancer) lead to reduce the dose during the intervention, for the safety of patients and medical staff. However, when the dose is reduced, image quality decreases, with a high level of noise and a very low contrast. Efficient restoration and denoising algorithms should overcome this drawback. We propose a spatio-temporal filter operating in a multi-scales space. This filter relies on a first order, motion compensated, recursive temporal denoising. Temporal high frequency content is first detected and then matched over time to allow for a strong denoising in the temporal axis. We study this filter in the curvelet domain and in the dual-tree complex wavelet domain, and compare those results to state of the art methods. Quantitative and qualitative analysis on both synthetic and real fluoroscopic sequences demonstrate that the proposed filter allows a great dose reduction. PMID- 26812706 TI - Robust Cell Detection of Histopathological Brain Tumor Images Using Sparse Reconstruction and Adaptive Dictionary Selection. AB - Successful diagnostic and prognostic stratification, treatment outcome prediction, and therapy planning depend on reproducible and accurate pathology analysis. Computer aided diagnosis (CAD) is a useful tool to help doctors make better decisions in cancer diagnosis and treatment. Accurate cell detection is often an essential prerequisite for subsequent cellular analysis. The major challenge of robust brain tumor nuclei/cell detection is to handle significant variations in cell appearance and to split touching cells. In this paper, we present an automatic cell detection framework using sparse reconstruction and adaptive dictionary learning. The main contributions of our method are: 1) A sparse reconstruction based approach to split touching cells; 2) An adaptive dictionary learning method used to handle cell appearance variations. The proposed method has been extensively tested on a data set with more than 2000 cells extracted from 32 whole slide scanned images. The automatic cell detection results are compared with the manually annotated ground truth and other state-of the-art cell detection algorithms. The proposed method achieves the best cell detection accuracy with a F1 score = 0.96. PMID- 26812707 TI - A Novel Regularization Technique for Microendoscopic Electrical Impedance Tomography. AB - A novel regularization technique is developed for end-fired microendoscopic electrical impedance tomography using the dual-mesh method. The new regularization technique coupled with appropriate forward modeling and inverse mesh design is shown to produce dramatically improved reconstructions over previous methods. 3D absolute and difference reconstructions from measured saline tank and ex vivo adipose and muscle tissue experiments are used to validate the approach. The ex vivo experiments are used as a surrogate for prostate tissue, which is the primary clinical application for the probe. Inclusion center of mass errors were less than 0.47 mm for tank experiments with inclusion depths and radial offsets ranging less than 3 mm and 1.5 mm, respectively. Absolute 3D reconstructions on the tissue show quantitatively good accuracy and the ability to spatially distinguish small tissue features (adipose strands of approximately 2.5 mm in width). The reconstruction algorithm developed provides strong evidence for the promise of surgical margin detection using microendoscopic EIT. PMID- 26812708 TI - Optical Profile Following High Hyperopia Correction With a 500-Hz Excimer Laser System. AB - PURPOSE: To evaluate corneal higher order aberrations after LASIK for the correction of high hyperopia using a 500-Hz excimer laser and optimized ablation profile. METHODS: Retrospective consecutive study including 51 eyes of 28 patients (age range: 21 to 54 years) with high hyperopia or hyperopic astigmatism (sphere >= 5.00 diopters). All cases underwent LASIK using the sixth generation Amaris excimer laser (SCHWIND eye-tech-solutions, Kleinostheim, Germany) and a femtosecond laser platform for flap creation. Postoperative changes in corneal higher order aberrations for the 4-, 5-, and 6-mm pupil diameters and corneal asphericity for 4.5 and 8 mm were represented at the end of the 6-month follow up. RESULTS: A significant increase in corneal root mean square higher order, spherical, and coma aberrations was observed 6 months after surgery (P < .01). Corneal asphericity for the 4.5-mm (Q45) and 8-mm (Q8) corneal diameter also changed significantly during the postoperative period (P < .01). Strehl ratio change was not statistically significant (P = .77). CONCLUSIONS: Correction of high hyperopia with LASIK significantly induces corneal higher order aberrations regardless of the physiologic level of photopic and mesopic pupil conditions. PMID- 26812709 TI - One-Year Outcomes of Femtosecond Laser-Assisted LASIK Following Previous Radial Keratotomy. AB - PURPOSE: To report the 1-year outcomes of LASIK in patients with previous radial keratotomy using a novel femtosecond laser platform. METHODS: The charts of 27 eyes of 18 patients who underwent femtosecond laser-assisted LASIK with the WaveLight FS200 laser (Alcon Laboratories, Inc., Fort Worth, TX) for consecutive hyperopia following previous radial keratotomy were retrospectively reviewed at a single private practice location. The preoperative characteristics, intraoperative details, and postoperative results were evaluated. RESULTS: All 27 eyes had successful femtosecond laser flap creation without significant intraoperative or postoperative complications. Uncorrected visual acuity significantly improved postoperatively to 0.13 +/- 0.13 logMAR at 12 months of follow-up (P < .0001). Postoperative spherical equivalent averaged 0.11 +/- 0.53 diopters. None of the patients lost any lines of corrected distance visual acuity during the postoperative period. CONCLUSIONS: The femtosecond laser technique described by this study resulted in a safe and effective way to deliver LASIK following previous radial keratotomy. Future investigations are needed to further validate the outcomes of this study. PMID- 26812710 TI - Objective Monitoring of Corneal Backward Light Scattering After Femtosecond Laser assisted LASIK. AB - PURPOSE: To investigate the changes in corneal backward light scattering, as measured by a rotating Scheimpflug camera with automated corneal densitometry software, in eyes treated with femtosecond laser-assisted LASIK (FS-LASIK). METHODS: The cornea was examined preoperatively and postoperatively at 1 day, 1 week, and 1, 3, and 6 months in 23 patients who underwent myopic FS-LASIK. Local analysis of corneal backscatter was performed on four concentric radial zones across a 12-mm diameter (0 to 2, 2 to 6, 6 to 10, and 10 to 12 mm) and at a different corneal depth (anterior 120 um, central and posterior 60 um). RESULTS: A statistically significant increase in corneal backward light scattering (P < .0001) was detected within the central 10 mm of the anterior cornea. The increase in corneal densitometry was gradually reversed over 6 months. The difference compared to preoperative values was no longer statistically significant at 3 and 6 months after surgery in the central cornea, whereas it remained significant in the mid-peripheral annulus (ranging from 6 to 10 mm), where the flap edge was located. CONCLUSIONS: FS-LASIK is followed by an increase in corneal backward light scattering during the early postoperative period that returns to baseline by 3 months. Whereas the increase in corneal densitometry at the flap edge location can be related to a scarring reaction, the explanation for such an increase in the central anterior cornea remains speculative. PMID- 26812711 TI - Evaluation of Total Corneal Thickness and Corneal Layers With Spectral-Domain Optical Coherence Tomography. AB - PURPOSE: To evaluate total corneal thickness and corneal layers in healthy young adults using spectral-domain optical coherence tomography and to describe its repeatability and reproducibility. METHODS: Eighty-six eyes from 86 healthy volunteers were prospectively and consecutively enrolled. Manual measurements of central corneal thickness (CCT) and central thickness of epithelium, Bowman's layer, stroma, and the Descemet-endothelium complex were performed using Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany). To assess the reliability of the repeated measurements, intraclass correlation coefficients and coefficients of variation were used. RESULTS: Mean CCT, epithelium, Bowman's layer, stroma, and Descemet-endothelium values were 555.50 +/- 29.64, 54.60 +/- 4.25, 16.70 +/- 1.73, 467.51 +/- 28.91, and 16.74 +/- 1.66 um, respectively. The intraclass correlation coefficients ranged from 0.746 (Bowman's layer) to 0.999 (CCT and stroma) and from 0.483 (Bowman's layer) to 0.995 (CCT) and 0.998 (stroma) for intraobserver repeatability and interobserver reproducibility, respectively. The measurements showed coefficients of variation lower than 11% in all cases. CONCLUSIONS: This study establishes a normal database for corneal thickness and all its layers in healthy young adults with spectral-domain optical coherence tomography. This device exhibited a high degree of intraobserver repeatability and interobserver reproducibility for all regions except Bowman's layer. PMID- 26812712 TI - New Scheimpflug Dynamic In Vivo Curve Analyses to Characterize Biomechanical Changes of the Cornea After Cross-linking for Progressive Keratoconus. AB - PURPOSE: To evaluate the effect of corneal cross-linking (CXL) in progressive keratoconus by applying in vivo static and dynamic Scheimpflug analyses. METHODS: In this longitudinal retrospective study, corneal topography and tomography (Pentacam HD) and dynamic Scheimpflug-based biomechanical analyses (CorvisST [CST]) of 24 eyes of 24 patients with progressive keratoconus before and 6 months after CXL were reviewed. New dynamic curve analyses, provided by Oculus Optikgerate, were performed to analyze corneal dynamics throughout the entire response to the CST air puff impulse. RESULTS: Besides subtle changes of topography and tomography, only the CorvisST predefined parameters peak distance (-0.5 mm) and radius of the intended cornea (+0.5 mm; P < .05) demonstrated statistically significant differences 6 months after CXL. Using new dynamic curve analyses, additional distinct changes of the corneal biomechanical characteristics after CXL were noted. CONCLUSIONS: Published results of corneal biomechanical changes after CXL for progressive keratoconus based on single, predefined CST parameters are inconsistent. The new dynamic curve analyses demonstrate distinct changes of the biomechanical properties of the cornea and might therefore be the next step in understanding in vivo analyses of corneal biomechanics. PMID- 26812714 TI - Sliding Keratoplasty Followed by Transepithelial Iontophoresis Collagen Cross linking for Pellucid Marginal Degeneration. AB - PURPOSE: To describe the changes in visual acuity and topographic analysis in a patient affected by advanced pellucid marginal degeneration (PMD). METHODS: A 59 year-old woman with bilateral PMD who was contact lens intolerant was treated by sliding keratoplasty before and 3 months after transepithelial (epi-on) iontophoresis collagen cross-linking (I-CXL) in one eye. Corrected distance visual acuity (CDVA), spherical equivalent and cylinder refraction, corneal topography, ultrasound pachymetry, and endothelial cell count were assessed at baseline and up to 12 months postoperatively. RESULTS: After 1 year of follow-up, CDVA increased from 20/200 to 20/50 and the videokeratographic patterns significantly improved. Endothelial cell counts did not change significantly (P > .05). CONCLUSIONS: Sliding keratoplasty combined with I-CXL was safe and effective in the treatment of advanced PMD. PMID- 26812713 TI - Evaluation of UVA Cytotoxicity for Human Endothelium in an Ex Vivo Corneal Cross linking Experimental Setting. AB - PURPOSE: To evaluate endothelial cytotoxicity after exposure of human corneas to ultraviolet-A (UVA) (lambda = 365 nm; 5.4 J/cm(2)) in an experimental ex vivo corneal cross-linking setting. METHODS: Sixteen pairs of human donor corneas were cut into two pieces. One piece of each cornea was treated with 0.025% riboflavin solution prior to UVA irradiation (5 minutes; 18 mW/cm(2)), whereas the other piece was not irradiated but treated with riboflavin (right eye) or preservation medium (left eye). By irradiating from the endothelial side, the UVA dosage applied to endothelial cells exceeded at least eight times the cytotoxic threshold established in animal models (0.65 J/cm(2)). Endothelial cell counts were performed by two independent investigators after storage (4 to 5 days at 31 degrees C) and staining (trypan blue, alizarin red). Normality (Q-Q plot; Shapiro Wilk test) and equivalence (mixed-effects modeling with a 10% equivalence threshold) of the endothelial cell counts of the different groups were evaluated. RESULTS: Equivalence of mean endothelial cell density between both groups was observed: 2,237 +/- 208 cells/mm(2) in UVA-irradiated pieces and 2,290 +/- 281 cells/mm(2) in control pieces (mean difference of 53 +/- 240 cells/mm(2) between both groups). CONCLUSIONS: Despite direct irradiation of human donor endothelium using the clinical dosage for cross-linking, equivalence in endothelial cell counts was observed between irradiated tissues and controls. Ex vivo human corneal endothelial cells seem to be far more resistant to riboflavin-enhanced UVA irradiation than previously estimated by animal experiments. PMID- 26812715 TI - Femtosecond Laser-Assisted LASIK Flap Complications. AB - PURPOSE: To discuss intraoperative and postoperative femtosecond laser-assisted LASIK flap complications and their management. METHODS: Review of published literature. RESULTS: Flap creation is a critical step in LASIK. The femtosecond laser has improved the overall predictability and safety of the lamellar incision, but complications can still occur during or after flap creation. Although many complications (eg, epithelial ingrowth and flap striae) were reduced with the femtosecond laser application, other specific complications have emerged, such as vertical gas breakthrough, opaque bubble layer, and transient light-sensitivity syndrome. CONCLUSIONS: The application of femtosecond laser technology to LASIK flap creation has increased greatly since its introduction. These lasers have improved the safety and predictability of the lamellar incision step. The majority of the femtosecond laser-assisted flap complications can be well managed without significant effects on refractive outcomes. PMID- 26812716 TI - Keratoconus Progression Induced by In Vitro Fertilization Treatment. AB - PURPOSE: To evaluate patients with keratoconus who manifested progression after in vitro fertilization (IVF) treatment. METHODS: Patients with keratoconus who received IVF treatment were included in this study. None of the patients became pregnant as a result of the IVF treatment. Progression of keratoconus was determined by changes in corrected distance visual acuity and/or topographic changes and subjective assessments. RESULTS: Three patients with keratoconus received IVF treatment and keratoconus progression was detected in all 6 eyes of the patients. The mean age of the patients was 32.3 +/- 3.6 years (range: 28 to 36 years) and the mean follow-up duration was 15.6 +/- 3.2 months (range: 12 to 18 months). The mean and the maximum keratometry values increased and corrected distance visual acuity decreased after 2.3 IVF treatments. CONCLUSIONS: Drugs used in IVF treatment increase estrogen levels, which may affect corneal biomechanics and induce progression of keratoconus. Corneal cross-linking treatment could be offered to minimize the risk of keratoconus progression before IVF treatment. PMID- 26812718 TI - Integrity of Intrastromal Arcuate Keratotomies Performed by Femtosecond Laser. PMID- 26812717 TI - Theoretical Effect of Lens Position and Corneal Curvature on the Near Focal Point of Multifocal Intraocular Lenses. AB - PURPOSE: To determine the effect of lens position and corneal curvature on the near focal point of different multifocal intraocular lenses. METHODS: Near focal points for various multifocal intraocular lenses were calculated using a refractive vergence formula. Median, high, and low values for lens position and corneal curvature were used. RESULTS: Lens position and corneal curvature both affected the theoretical near point of multifocal intraocular lenses. The effect was more pronounced for lower power adds. There was overlap of near focal points for the different near adds of the Tecnis multifocal lenses (AMO, Abbott Park, IL) across the range of lens positions and corneal curvatures seen in a normal population. CONCLUSIONS: Clinicians need to be aware of the effect of lens position and corneal curvature on the near focal point of intraocular lenses. PMID- 26812719 TI - Complications From Corneal Cross-linking for Keratoconus in Pediatric Patients. PMID- 26812720 TI - Intraoperative Wavefront Aberrometry for Toric Intraocular Lens Placement in Eyes With a History of Refractive Surgery. PMID- 26812722 TI - Out-of-Sample Generalizations for Supervised Manifold Learning for Classification. AB - Supervised manifold learning methods for data classification map high-dimensional data samples to a lower dimensional domain in a structure-preserving way while increasing the separation between different classes. Most manifold learning methods compute the embedding only of the initially available data; however, the generalization of the embedding to novel points, i.e., the out-of-sample extension problem, becomes especially important in classification applications. In this paper, we propose a semi-supervised method for building an interpolation function that provides an out-of-sample extension for general supervised manifold learning algorithms studied in the context of classification. The proposed algorithm computes a radial basis function interpolator that minimizes an objective function consisting of the total embedding error of unlabeled test samples, defined as their distance to the embeddings of the manifolds of their own class, as well as a regularization term that controls the smoothness of the interpolation function in a direction-dependent way. The class labels of test data and the interpolation function parameters are estimated jointly with an iterative process. Experimental results on face and object images demonstrate the potential of the proposed out-of-sample extension algorithm for the classification of manifold-modeled data sets. PMID- 26812723 TI - Visual Object Tracking Performance Measures Revisited. AB - The problem of visual tracking evaluation is sporting a large variety of performance measures, and largely suffers from lack of consensus about which measures should be used in experiments. This makes the cross-paper tracker comparison difficult. Furthermore, as some measures may be less effective than others, the tracking results may be skewed or biased toward particular tracking aspects. In this paper, we revisit the popular performance measures and tracker performance visualizations and analyze them theoretically and experimentally. We show that several measures are equivalent from the point of information they provide for tracker comparison and, crucially, that some are more brittle than the others. Based on our analysis, we narrow down the set of potential measures to only two complementary ones, describing accuracy and robustness, thus pushing toward homogenization of the tracker evaluation methodology. These two measures can be intuitively interpreted and visualized and have been employed by the recent visual object tracking challenges as the foundation for the evaluation methodology. PMID- 26812724 TI - Super-Resolution of Multi-Observed RGB-D Images Based on Nonlocal Regression and Total Variation. AB - There is growing demand for accuracy in image processing and visualization, and the super-resolution (SR) technique for multi-observed RGB-D images has become popular, because it provides space-redundant information and produces a detailed reconstruction even with a large magnification factor. This technique has been thoroughly investigated in recent years. Nevertheless, technical challenges remain, such as finding sub-pixel correspondences with low-resolution (LR) observations, exploiting space-redundant information, formulating space homogeneity constraints, and leveraging cross-image similarities in structures. To address these challenges, this paper proposes a unified optimization framework to estimate both the super-resolved RGB image and the super-resolved depth image from the multi-observed LR RGB-D images using their correlations. Using depth assisted cross-image correspondences, the RGB image SR problem is formulated as an effective regularization function by incorporating the normalized bilateral total variation regularizer, and it is efficiently solved by a first-order primal dual algorithm. The depth image SR estimate can be obtained by minimizing a nonlocal regression-based energy, which integrates the structural cues of the super-resolved RGB image in a detail-preserving fashion. Essentially, our unified optimization framework uses the RGB image and depth image as a priori knowledge that the SR process uses for better accuracy. Our extensive experiments on public RGB-D benchmarks and real data and our quantitative comparison with several state of-the-art methods demonstrate the superiority of our method in terms of accuracy, versatility, and reliability of details and sharp feature preservation. PMID- 26812725 TI - Vis-A-Ware: Integrating Spatial and Non-Spatial Visualization for Visibility Aware Urban Planning. AB - 3D visibility analysis plays a key role in urban planning for assessing the visual impact of proposed buildings on the cityscape. A call for proposals typically yields around 30 candidate buildings that need to be evaluated with respect to selected viewpoints. Current visibility analysis methods are very time consuming and limited to a small number of viewpoints. Further, analysts neither have measures to evaluate candidates quantitatively, nor to compare them efficiently. The primary contribution of this work is the design study of Vis-A Ware, a visualization system to qualitatively and quantitatively evaluate, rank, and compare visibility data of candidate buildings with respect to a large number of viewpoints. Vis-A-Ware features a 3D spatial view of an urban scene and non spatial views of data derived from visibility evaluations, which are tightly integrated by linked interaction. To enable a quantitative evaluation we developed four metrics in accordance with experts from urban planning. We illustrate the applicability of Vis-A-Ware on the basis of a use case scenario and present results from informal feedback sessions with domain experts from urban planning and development. This feedback suggests that Vis-A-Ware is a valuable tool for visibility analysis allowing analysts to answer complex questions more efficiently and objectively. PMID- 26812726 TI - A Study of Layout, Rendering, and Interaction Methods for Immersive Graph Visualization. AB - Information visualization has traditionally limited itself to 2D representations, primarily due to the prevalence of 2D displays and report formats. However, there has been a recent surge in popularity of consumer grade 3D displays and immersive head-mounted displays (HMDs). The ubiquity of such displays enables the possibility of immersive, stereoscopic visualization environments. While techniques that utilize such immersive environments have been explored extensively for spatial and scientific visualizations, contrastingly very little has been explored for information visualization. In this paper, we present our considerations of layout, rendering, and interaction methods for visualizing graphs in an immersive environment. We conducted a user study to evaluate our techniques compared to traditional 2D graph visualization. The results show that participants answered significantly faster with a fewer number of interactions using our techniques, especially for more difficult tasks. While the overall correctness rates are not significantly different, we found that participants gave significantly more correct answers using our techniques for larger graphs. PMID- 26812727 TI - Motion Capture With Ellipsoidal Skeleton Using Multiple Depth Cameras. AB - This paper introduces a novel motion capturing framework which works by minimizing the fitting error between an ellipsoid based skeleton and the input point cloud data captured by multiple depth cameras. The novelty of this method comes from that it uses the ellipsoids equipped with the spherical harmonics encoded displacement and normal functions to capture the geometry details of the tracked object. This method is also integrated with a mechanism to avoid collisions of bones during the motion capturing process. The method is implemented parallelly with CUDA on GPU and has a fast running speed without dedicated code optimization. The errors of the proposed method on the data from Berkeley Multimodal Human Action Database (MHAD) are within a reasonable range compared with the ground truth results. Our experiment shows that this method succeeds on many challenging motions which are failed to be reported by Microsoft Kinect SDK and not tested by existing works. In the comparison with the state-of art marker-less depth camera based motion tracking work our method shows advantages in both robustness and input data modality. PMID- 26812728 TI - Discriminative Feature Extraction via Multivariate Linear Regression for SSVEP Based BCI. AB - Many of the most widely accepted methods for reliable detection of steady-state visual evoked potentials (SSVEPs) in the electroencephalogram (EEG) utilize canonical correlation analysis (CCA). CCA uses pure sine and cosine reference templates with frequencies corresponding to the visual stimulation frequencies. These generic reference templates may not optimally reflect the natural SSVEP features obscured by the background EEG. This paper introduces a new approach that utilizes spatio-temporal feature extraction with multivariate linear regression (MLR) to learn discriminative SSVEP features for improving the detection accuracy. MLR is implemented on dimensionality-reduced EEG training data and a constructed label matrix to find optimally discriminative subspaces. Experimental results show that the proposed MLR method significantly outperforms CCA as well as several other competing methods for SSVEP detection, especially for time windows shorter than 1 second. This demonstrates that the MLR method is a promising new approach for achieving improved real-time performance of SSVEP BCIs. PMID- 26812729 TI - Low-Complexity Adaptive Threshold Detection for Molecular Communication. AB - This paper studies detection algorithms for diffusion-based molecular communication systems, where molecules freely diffuse as information carrier from a transmitter to a receiver in a fluid medium. The main limitations are strong intersymbol interference due to the random propagation of the molecules, and the low-energy/low-complexity assumption regarding future implementations in so called nanomachines. In this contribution, a new biologically inspired detection algorithm suitable for binary signaling, named adaptive threshold detection, is proposed, which deals with these limitations. The proposed detector is of low complexity, does not require explicit channel knowledge, and seems to be biologically reasonable. Numerical results demonstrate that the proposed detector can outperform the common low-complexity fixed threshold detector under certain conditions. As a benchmark, maximum-likelihood sequence estimation (MLSE) and reduced-state sequence estimation (RSSE) are also analyzed by means of numerical simulations. In addition, the effect of molecular denaturation on the detection performances is studied. It is shown that denaturation generally improves the detection performances, while RSSE is able to outperform MLSE in the case of no denaturation. PMID- 26812730 TI - Extracting Coevolutionary Features from Protein Sequences for Predicting Protein Protein Interactions. AB - Knowing the ways proteins interact with each other are crucial to our understanding of the functional mechanisms of proteins. It is for this reason that different approaches have been developed in attempts to predict protein protein interactions (PPIs) computationally. Among them, the sequence-based approaches are preferred to the others as they do not require any information about protein properties to perform their tasks. Instead, most sequence-based approaches make use of feature extraction methods to extract features directly from protein sequences so that for each protein sequence, we can construct a feature vector. The feature vectors of every pair of proteins are then concatenated to form two classes of interacting and non-interacting proteins. The prediction of whether or not two proteins interact with each other is then formulated as a classification problem. How accurate PPI predictions can be made therefore depends on how good the features are that can be extracted from the protein sequences to allow interacting or non-interacting to be best distinguished. To do so, instead of extracting such features from individual protein sequences independently of the other protein in the same pair, we propose to jointly consider features from both sequences in a protein pair during the feature extraction process through using a novel coevolutionary feature extraction approach called CoFex. Coevolutionary features extracted by CoFex refer to the covariations found at coevolving positions. Based on the presence and absence of these coevolutionary features in the sequences of two proteins, feature vectors can be composed for pairs of proteins rather than individual proteins. The experiment results show that CoFex is a promising feature extraction approach and can improve the performance of PPI prediction. PMID- 26812731 TI - Predicting nsSNPs that Disrupt Protein-Protein Interactions Using Docking. AB - The human genome contains a large number of protein polymorphisms due to individual genome variation. How many of these polymorphisms lead to altered protein-protein interaction is unknown. We have developed a method to address this question. The intersection of the SKEMPI database (of affinity constants among interacting proteins) and CAPRI 4.0 docking benchmark was docked using HADDOCK, leading to a training set of 166 mutant pairs. A random forest classifier based on the differences in resulting docking scores between the 166 mutant pairs and their wild-types was used, to distinguish between variants that have either completely or partially lost binding ability. Fifty percent of non binders were correctly predicted with a false discovery rate of only 2 percent. The model was tested on a set of 15 HIV-1 - human, as well as seven human- human glioblastoma-related, mutant protein pairs: 50 percent of combined non-binders were correctly predicted with a false discovery rate of 10 percent. The model was also used to identify 10 protein-protein interactions between human proteins and their HIV-1 partners that are likely to be abolished by rare non-synonymous single-nucleotide polymorphisms (nsSNPs). These nsSNPs may represent novel and potentially therapeutically-valuable targets for anti-viral therapy by disruption of viral binding. PMID- 26812732 TI - Emerging Security Mechanisms for Medical Cyber Physical Systems. AB - The following decade will witness a surge in remote health-monitoring systems that are based on body-worn monitoring devices. These Medical Cyber Physical Systems (MCPS) will be capable of transmitting the acquired data to a private or public cloud for storage and processing. Machine learning algorithms running in the cloud and processing this data can provide decision support to healthcare professionals. There is no doubt that the security and privacy of the medical data is one of the most important concerns in designing an MCPS. In this paper, we depict the general architecture of an MCPS consisting of four layers: data acquisition, data aggregation, cloud processing, and action. Due to the differences in hardware and communication capabilities of each layer, different encryption schemes must be used to guarantee data privacy within that layer. We survey conventional and emerging encryption schemes based on their ability to provide secure storage, data sharing, and secure computation. Our detailed experimental evaluation of each scheme shows that while the emerging encryption schemes enable exciting new features such as secure sharing and secure computation, they introduce several orders-of-magnitude computational and storage overhead. We conclude our paper by outlining future research directions to improve the usability of the emerging encryption schemes in an MCPS. PMID- 26812733 TI - A Visual Interface for Querying Heterogeneous Phylogenetic Databases. AB - Despite the recent growth in the number of phylogenetic databases, access to these wealth of resources remain largely tool or form-based interface driven. It is our thesis that the flexibility afforded by declarative query languages may offer the opportunity to access these repositories in a better way, and to use such a language to pose truly powerful queries in unprecedented ways. In this paper, we propose a substantially enhanced closed visual query language, called PhyQL, that can be used to query phylogenetic databases represented in a canonical form. The canonical representation presented helps capture most phylogenetic tree formats in a convenient way, and is used as the storage model for our PhyloBase database for which PhyQL serves as the query language. We have implemented a visual interface for the end users to pose PhyQL queries using visual icons, and drag and drop operations defined over them. Once a query is posed, the interface translates the visual query into a Datalog query for execution over the canonical database. Responses are returned as hyperlinks to phylogenies that can be viewed in several formats using the tree viewers supported by PhyloBase. Results cached in PhyQL buffer allows secondary querying on the computed results making it a truly powerful querying architecture. PMID- 26812734 TI - An Autonomous Wireless Sensor Node With Asynchronous ECG Monitoring in 0.18 MU m CMOS. AB - The design of a 13.56 MHz/402 MHz autonomous wireless sensor node with asynchronous ECG monitoring for near field communication is presented. The sensor node consists of an RF energy harvester (RFEH), a power management unit, an ECG readout, a data encoder and an RF backscattering transmitter. The energy harvester supplies the system with 1.25 V and offers a power conversion efficiency of 19% from a -13 dBm RF source at 13.56 MHz. The power management unit regulates the output voltage of the RFEH to supply the ECG readout with VECG = 0.95 V and the data encoder with VDE = 0.65 V . The ECG readout comprises an analog front-end (low noise amplifier and programmable voltage to current converter) and an asynchronous level crossing ADC with 8 bits resolution. The ADC output is encoded by a pulse generator that drives a backscattering transmitter at 402 MHz. The total power consumption of the sensor node circuitry is 9.7 MU W for a data rate of 90 kb/s and a heart rate of 70 bpm. The chip has been designed in a 0.18 MUm CMOS process and shows superior RF input power sensitivity and lower power consumption when compared to previous works. PMID- 26812736 TI - Nonparametric Density Estimation Based on Self-Organizing Incremental Neural Network for Large Noisy Data. AB - With the ongoing development and expansion of communication networks and sensors, massive amounts of data are continuously generated in real time from real environments. Beforehand, prediction of a distribution underlying such data is difficult; furthermore, the data include substantial amounts of noise. These factors make it difficult to estimate probability densities. To handle these issues and massive amounts of data, we propose a nonparametric density estimator that rapidly learns data online and has high robustness. Our approach is an extension of both kernel density estimation (KDE) and a self-organizing incremental neural network (SOINN); therefore, we call our approach KDESOINN. An SOINN provides a clustering method that learns about the given data as networks of prototype of data; more specifically, an SOINN can learn the distribution underlying the given data. Using this information, KDESOINN estimates the probability density function. The results of our experiments show that KDESOINN outperforms or achieves performance comparable to the current state-of-the-art approaches in terms of robustness, learning time, and accuracy. PMID- 26812735 TI - A Multi-Modality CMOS Sensor Array for Cell-Based Assay and Drug Screening. AB - In this paper, we present a fully integrated multi-modality CMOS cellular sensor array with four sensing modalities to characterize different cell physiological responses, including extracellular voltage recording, cellular impedance mapping, optical detection with shadow imaging and bioluminescence sensing, and thermal monitoring. The sensor array consists of nine parallel pixel groups and nine corresponding signal conditioning blocks. Each pixel group comprises one temperature sensor and 16 tri-modality sensor pixels, while each tri-modality sensor pixel can be independently configured for extracellular voltage recording, cellular impedance measurement (voltage excitation/current sensing), and optical detection. This sensor array supports multi-modality cellular sensing at the pixel level, which enables holistic cell characterization and joint-modality physiological monitoring on the same cellular sample with a pixel resolution of 80 MUm * 100 MUm. Comprehensive biological experiments with different living cell samples demonstrate the functionality and benefit of the proposed multi-modality sensing in cell-based assay and drug screening. PMID- 26812737 TI - Impulsive Synchronization of Reaction-Diffusion Neural Networks With Mixed Delays and Its Application to Image Encryption. AB - This paper presents a new impulsive synchronization criterion of two identical reaction-diffusion neural networks with discrete and unbounded distributed delays. The new criterion is established by applying an impulse-time-dependent Lyapunov functional combined with the use of a new type of integral inequality for treating the reaction-diffusion terms. The impulse-time-dependent feature of the proposed Lyapunov functional can capture more hybrid dynamical behaviors of the impulsive reaction-diffusion neural networks than the conventional impulse time-independent Lyapunov functions/functionals, while the new integral inequality, which is derived from Wirtinger's inequality, overcomes the conservatism introduced by the integral inequality used in the previous results. Numerical examples demonstrate the effectiveness of the proposed method. Later, the developed impulsive synchronization method is applied to build a spatiotemporal chaotic cryptosystem that can transmit an encrypted image. The experimental results verify that the proposed image-encrypting cryptosystem has the advantages of large key space and high security against some traditional attacks. PMID- 26812738 TI - A Scoring Scheme for Online Feature Selection: Simulating Model Performance Without Retraining. AB - Increasing the number of features increases the complexity of a model even if the additional feature does not improve its decision-making capacity. Irrelevant features may also cause overfitting and reduce interpretability of the concerned model. It is, therefore, important that the features are optimally selected before a model is built. In the case of online learning, new instances are periodically discovered, and the respective model is tactically retrained as required. Similarly, there are many real-life situations where hundreds of new features are discovered periodically, and the existing model needs to be retrained or tested for its performance improvement. Supervised selection of feature subset usually requires creation of multiple suboptimal models, thus incurring time-intensive computations. Unsupervised selections, although faster, largely rely on some subjective definition of feature relevance. In this paper, we introduce a score that accurately determines the importance of the features. The proposed score is appropriate for online feature selection scenarios for its low time complexity and ability to interpret performance improvement of the current model after the addition of a new feature, without invoking a retraining. PMID- 26812739 TI - Learning a Coupled Linearized Method in Online Setting. AB - Based on the alternating direction method of multipliers, in this paper, we propose, analyze, and test a coupled linearized method, which aims to minimize an unconstrained problem consisting of a loss term and a regularization term in an online setting. To solve this problem, we first transform it into an equivalent constrained minimization problem with a separable structure. Then, we split the corresponding augmented Lagrangian function and minimize the resulting subproblems distributedly with one variable by fixing another one. This method is easy to execute without calculating matrix inversion by implementing three linearized operations per iteration, and at each iteration, we can obtain a closed-form solution. In particular, our update rule contains the well-known soft thresholding operator as a special case. Moreover, upper bound on the regret of the proposed method is analyzed. Under some mild conditions, it can achieve O(1/?T) convergence rate for convex learning problems and O((log T)/ T) for strongly convex learning. Numerical experiments and comparisons with several state-of-the-art methods are reported, which demonstrate the efficiency and effectiveness of our approach. PMID- 26812740 TI - Graph Theory-Based Pinning Synchronization of Stochastic Complex Dynamical Networks. AB - This paper is concerned with the adaptive pinning synchronization problem of stochastic complex dynamical networks (CDNs). Based on algebraic graph theory and Lyapunov theory, pinning controller design conditions are derived, and the rigorous convergence analysis of synchronization errors in the probability sense is also conducted. Compared with the existing results, the topology structures of stochastic CDN are allowed to be unknown due to the use of graph theory. In particular, it is shown that the selection of nodes for pinning depends on the unknown lower bounds of coupling strengths. Finally, an example on a Chua's circuit network is given to validate the effectiveness of the theoretical results. PMID- 26812741 TI - High-Order Measurements for Residual Classifiers. AB - Residual classifiers are common in dictionary-based multiclass classification. This paper proposes the concept of performance functions for residual classifiers. A performance function for multiclass classifications is a conceptual measurement function that combines local and global measurements. In general, the performance function is nonlinear. To explore the properties of the performance function, we employ the Taylor series expansion technique and derive a family of measurement functions. Specifically, the linear measurement and the quadratic measurement (QM) are derived. By exploiting the effect of the higher order terms in the performance function as well as the fundamental nondecreasing constrain, we derive the normalized QM (NQM). We present the classifier for multiclass classification using the proposed measurements. The proposed algorithms are tested against frontal faces and handwritten digit recognition tasks. Our tests show that the QM classifier achieves competitive classification results compared with baseline methods. NQM shows better stability with different parameter configurations. PMID- 26812742 TI - Distributed Recurrent Neural Networks for Cooperative Control of Manipulators: A Game-Theoretic Perspective. AB - This paper considers cooperative kinematic control of multiple manipulators using distributed recurrent neural networks and provides a tractable way to extend existing results on individual manipulator control using recurrent neural networks to the scenario with the coordination of multiple manipulators. The problem is formulated as a constrained game, where energy consumptions for each manipulator, saturations of control input, and the topological constraints imposed by the communication graph are considered. An implicit form of the Nash equilibrium for the game is obtained by converting the problem into its dual space. Then, a distributed dynamic controller based on recurrent neural networks is devised to drive the system toward the desired Nash equilibrium to seek the optimal solution of the cooperative control. Global stability and solution optimality of the proposed neural networks are proved in the theory. Simulations demonstrate the effectiveness of the proposed method. PMID- 26812743 TI - Real-Time Fault Detection Approach for Nonlinear Systems and its Asynchronous T-S Fuzzy Observer-Based Implementation. AB - This paper is concerned with a real-time observer-based fault detection (FD) approach for a general type of nonlinear systems in the presence of external disturbances. To this end, in the first part of this paper, we deal with the definition and the design condition for an L infinity / L 2 type of nonlinear observer-based FD systems. This analytical framework is fundamental for the development of real-time nonlinear FD systems with the aid of some well established techniques. In the second part, we address the integrated design of the L infinity / L 2 observer-based FD systems by applying Takagi-Sugeno (T-S) fuzzy dynamic modeling technique as the solution tool. This fuzzy observer-based FD approach is developed via piecewise Lyapunov functions, and can be applied to the case that the premise variables of the FD system is nonsynchronous with the premise variables of the fuzzy model of the plant. In the end, a case study on the laboratory setup of three-tank system is given to show the efficiency of the proposed results. PMID- 26812744 TI - An Incremental Type-2 Meta-Cognitive Extreme Learning Machine. AB - Existing extreme learning algorithm have not taken into account four issues: 1) complexity; 2) uncertainty; 3) concept drift; and 4) high dimensionality. A novel incremental type-2 meta-cognitive extreme learning machine (ELM) called evolving type-2 ELM (eT2ELM) is proposed to cope with the four issues in this paper. The eT2ELM presents three main pillars of human meta-cognition: 1) what-to-learn; 2) how-to-learn; and 3) when-to-learn. The what-to-learn component selects important training samples for model updates by virtue of the online certainty-based active learning method, which renders eT2ELM as a semi-supervised classifier. The how-to learn element develops a synergy between extreme learning theory and the evolving concept, whereby the hidden nodes can be generated and pruned automatically from data streams with no tuning of hidden nodes. The when-to-learn constituent makes use of the standard sample reserved strategy. A generalized interval type-2 fuzzy neural network is also put forward as a cognitive component, in which a hidden node is built upon the interval type-2 multivariate Gaussian function while exploiting a subset of Chebyshev series in the output node. The efficacy of the proposed eT2ELM is numerically validated in 12 data streams containing various concept drifts. The numerical results are confirmed by thorough statistical tests, where the eT2ELM demonstrates the most encouraging numerical results in delivering reliable prediction, while sustaining low complexity. PMID- 26812745 TI - A Nonhomogeneous Cuckoo Search Algorithm Based on Quantum Mechanism for Real Parameter Optimization. AB - Cuckoo search (CS) algorithm is a nature-inspired search algorithm, in which all the individuals have identical search behaviors. However, this simple homogeneous search behavior is not always optimal to find the potential solution to a special problem, and it may trap the individuals into local regions leading to premature convergence. To overcome the drawback, this paper presents a new variant of CS algorithm with nonhomogeneous search strategies based on quantum mechanism to enhance search ability of the classical CS algorithm. Featured contributions in this paper include: 1) quantum-based strategy is developed for nonhomogeneous update laws and 2) we, for the first time, present a set of theoretical analyses on CS algorithm as well as the proposed algorithm, respectively, and conclude a set of parameter boundaries guaranteeing the convergence of the CS algorithm and the proposed algorithm. On 24 benchmark functions, we compare our method with five existing CS-based methods and other ten state-of-the-art algorithms. The numerical results demonstrate that the proposed algorithm is significantly better than the original CS algorithm and the rest of compared methods according to two nonparametric tests. PMID- 26812748 TI - Severe Vascular Complications Of Acute Pancreatitis. AB - Acute pancreatitis (AP) develops as a result of the imbalance of the mechanisms inhibiting the activity of enzymes in the pancreatic cells, which causes their autoactivation in the pancreas. The incidence of AP ranges from 10 up to 100 cases per 100,000 population per year in different parts of the world. The overall mortality rate for acute pancreatitis is 10-15%. The mortality rate in patients diagnosed with the severe form of acute pancreatitis is up to 30-40%. MATERIAL AND METHODS: The study included 10 patients treated due to acute pancreatitis in two surgical departments run by one of the authors (S.G.) in the years 2004-2014, who developed a serious complication in the form of haemorrhage into the inflammatory tumour/pancreatic cyst or an adjacent organ. Haemorrhage was diagnosed based on the clinical picture, most often a sudden drop in blood pressure, peritonitis symptoms and imaging findings--abdominal ultrasound and abdominal computed tomography. Therapeutic methods included conservative treatment, endovascular embolisation and, in the absence of efficacy of the above mentioned methods, surgical treatment. Patients age and gender, the etiological factor, comorbidities, Atlanta Classification, treatment outcomes and mortality rate were assessed. RESULTS: Alcohol was the most common etiological factor in the investigated AP cases. The patients received conservative treatment, interventional radiology treatment (endovascular embolisation) or surgical treatment. In the study group, 6 patients required surgical treatment, 3 patients received invasive radiology treatment, and conservative treatment was used in one patient. The mortality rate in the study group was 30%. CONCLUSIONS: Haemorrhages into the inflammatory cisterns or adjacent organs (stomach, transverse colon mesentery) secondary to AP are the most severe complications, which are difficult to manage. The successful use of interventional radiology methods to inhibit and prevent the recurrence of bleeding in some of the patients is a significant milestone. PMID- 26812749 TI - The Use Of The VEINES-QOL/Sym Questionnaire In Patients Operated For Varicose Veins. AB - Venous insufficiency is a common, chronic disease that affects nearly half of the population in highly developed countries. The vast majority of affected patients suffer from varicose veins (VV). Recently, the priority in medicine has been patient satisfaction with treatment and high quality of life. Therefore, disease specific questionnaires that measure quality of life have been developed. One of these is VEINES-QOL/Sym with two subscales that assess quality of life and disease symptoms. To date, it has been used to examine patients with venous ulcers and thrombosis. No data are available concerning the use of VEINES to assess patients after VV surgery. The aim of the study was to investigate the change in QOL after VV surgery and verify the usefulness of VEINES in daily phlebological practice. MATERIAL AND METHODS: The study recruited 69 patients (CEAP class C2-C3) in need of surgery for VV. The patients responded 2 hours before surgery and after 3 months. Patients were differentiated into several categories according to CEAP stage, age, sex, BMI, the use/lack of compression therapy, and education level. RESULTS: The quality of life increased significantly in C3 patients and in patients over the age of 50. Quality of life increased significantly in all patients regardless of education. There were no differences between groups differentiated according to sex, the use or lack of compression therapy, or BMI. CONCLUSIONS: The VEINES-QOL/Sym questionnaire can be used in daily phlebological practice to assess patients before and after surgical treatment of VV. VEINES-QOL/Sym is reliable and highly valid. PMID- 26812750 TI - Risk Factors Of Pancreatitis After Endoscopic Retrograde Cholangiopancreatography -A Retrospective Cohort Study. AB - Endoscopic retrograde cholangiopancreatography (ERCP) is the most important non surgical procedure in serious pancreatic and biliary diseases, still burdened with the risk of severe complications. The objective of the study was to distinguish factors which could increase the risk of occurrence of ERCP complication in the form of pancreatitis. MATERIAL AND METHODS: The study included 452 patients who had undergone ERCP. Patients' records were retrospectively analyzed from the aspect of demographic data, indications for the procedure, type and course of the procedure, type and severity of complications, width of the common bile duct (CBD), concomitant diseases and administered medicines which might increase the risk of complications. RESULTS: In 35 patients (7.7%) a complication occurred in the form of pancreatitis (AP). A severe course was confirmed in 11 patients (31%). Cholelithiasis constituted approximately 2/3 of indications for ERCP. AP after ERCP was significantly more often observed in the group of patients aged under 40 (22.9% vs 8.6%; p<0.05). Narrow biliary ducts (3-8 mm) were the factor increasing the frequency of development of AP (25.9% vs 45%; p<0.05). Death occurred in 5 patients (1.1%), including 4 patients (0.96%) in the group without complications, and in 1 patient (2.85%) with complicated AP. CONCLUSIONS: ERCP is a very valuable procedure in clinical treatment; however, it is burdened with the risk of complications, such as AP, bleeding, or duodenal perforation. A group especially exposed to the risk of complications in the form of AP are young patients aged under 40 with a narrow CBD. PMID- 26812751 TI - Analysis Of Risk Factors Of Positive Peritoneal Cytology In Patients Treated For Gastric Cancer--Preliminary Report. AB - Presence of free gastric cancer cells in the peritoneal cavity of patients who underwent surgical treatment for gastric cancer is a negative prognostic factor and caused rapid disease recurrence, manifested as peritoneal metastases. Positive peritoneal cytology despite lack of visible peritoneal metastases was regarded as M1 class in the TNM classification (7th edition) in 2010. The aim of the study was to analyze factors associated with positive peritoneal cytology and identify groups of patients in whom diagnostic laparoscopy plus peritoneal lavage in the diagnostic process could affect therapeutic decisions. MATERIAL AND METHODS: The study enrolled patients with gastric cancer who underwent surgical treatment at the Department of Surgery, Wielkopolskie Oncology Center in Poznan. During the laparotomy, after opening of the peritoneal cavity, 200 ml of physiological saline at 37 degrees C was administered in the tumor region. After this fluid was mixed, 100 ml of lavage fluid was collected. This fluid was subsequently spun many times to obtain sediment for cytology and immunohistochemistry investigation using anti-BerEp-4, CK 7/20, and B72.3. Results of peritoneal cytology were analyzed jointly with clinical factors- patient's age, sex and pathology factors--tumor invasion, involvement of lymph nodes, histological grade, histological type according to Lauren and localization of the cancer in the stomach. RESULTS: Analysis of the peritoneal fluid for presence of free cancer cells was done in 51 patients. Positive peritoneal cytology was found in 12 (23.5%) patients. In the group of patients with positive cytology, all patients had T3/T4 tumors and all were found to have lymph node metastases, while G3 cancer was found in 83.3% of patients. In patients with positive cytology, diffuse gastric cancer according to Lauren predominated (9 of 12 patients, 75%), while in patients with negative cytology--intestinal type (20 of 39 patients, 51.2%). In the group of patients with positive histology, the whole stomach was involved by the cancer process in 7 of 12 patients (58.3%), while in the group with negative histology, in 29 of 39 patients the tumor was located in the gastric body and prepyloric part (74.4%). CONCLUSIONS: Based on this study we can conclude that determinants of positive peritoneal cytology include: tumor stage T3/T4, N+, G3, cancer located in the whole stomach, diffuse histological type according to Lauren. PMID- 26812752 TI - Own Experience From The Use Of A Substitute Of An Allogeneic Acellular Dermal Matrix Revitalized With In Vitro Cultured Skin Cells In Clinical Practice. AB - As a result of the removal of cells from human allogeneic dermis, a collagen scaffold is obtained, which can be populated de novo with autologous/allogeneic skin cells and transplanted onto the area of skin loss. The optimal method for production of acellular dermal matrices (ADM) has been selected. Three female patients (a mean age of 54 years) were subjected to the transplantation of either autologous or allogeneic keratinocytes and fibroblasts into the holes of acellular dermal matrix (ADM) mesh graft. The method for burn wound treatment based on the use of a viable dermal-epidermal skin substitute (based on ADM and in vitro cultured fibroblasts and keratinocytes) may be the optimal method of burn treatment. PMID- 26812753 TI - The Use Of Negative Pressure Wound Therapy (NPWT) In The Management Of Enteroatmospheric Fistula--Case Report And Literature Review. AB - An enteric fistula that occurs in an open abdomen is called an enteroatmospheric fistula (EAF) and is the most challenging complication for a surgical team to deal with. The treatment of EAF requires a multidisciplinary approach. First of all, sepsis has to be managed. Any fluid, electrolyte and metabolic disorders need to be corrected. Oral intake must be stopped and total parenteral nutrition introduced. The control and drainage of the effluent from the fistula is a separate issue. Since there are no fixed algorithms for the treatment of EAF, surgeons need to develop their own, often highly unconventional solutions. We present the case of a 24-year-old man who developed enteroatmospheric fistula after laparotomy and relaparotomy due to acute necrotic pancreatitis. Both the laparostomy and the fistula were successfully managed using modified negative pressure wound therapy. The literature regarding this issue was also reviewed. PMID- 26812754 TI - A Rare Presentation Of An Ectopic Breast Tissue In Axilla. AB - Accessory breast tissue is rare accounting to less than 1% cases seen in females. It is usually bilateral. We report a case of 24-year-old woman with a lump in the left axilla in view of its rarity and made a differential diagnosis of fibroadenoma, which following the investigations and histopathological report was confirmed as revealed fibroadenoma in the axilla. It should also be considered as a differential diagnosis for all axillary swellings. PMID- 26812755 TI - Parastomal Hernia--Contemporary Methods Of Treatment. PMID- 26812756 TI - Searching bioremediation patents through Cooperative Patent Classification (CPC). AB - Patent classification systems have traditionally evolved independently at each patent jurisdiction to classify patents handled by their examiners to be able to search previous patents while dealing with new patent applications. As patent databases maintained by them went online for free access to public as also for global search of prior art by examiners, the need arose for a common platform and uniform structure of patent databases. The diversity of different classification, however, posed problems of integrating and searching relevant patents across patent jurisdictions. To address this problem of comparability of data from different sources and searching patents, WIPO in the recent past developed what is known as International Patent Classification (IPC) system which most countries readily adopted to code their patents with IPC codes along with their own codes. The Cooperative Patent Classification (CPC) is the latest patent classification system based on IPC/European Classification (ECLA) system, developed by the European Patent Office (EPO) and the United States Patent and Trademark Office (USPTO) which is likely to become a global standard. This paper discusses this new classification system with reference to patents on bioremediation. PMID- 26812758 TI - Inadequate water, sanitation and hygiene in the South Pacific: how might it be impacting children? AB - It is detrimental to anyone's health to live with conditions of inadequate water, sanitation and hygiene (WaSH). Research suggests that the impact is greatest on children, and that poor WaSH conditions during the formative years can lead to decreased physical, mental and social well-being throughout one's life. Little research has investigated how such poor WaSH conditions are negatively impacting children in the South Pacific region, and hence contributing to disease and social burden. To increase children's opportunities to develop physically and intellectually in a healthy and sustained manner, it is important that practitioners take a holistic approach to improving WaSH by acknowledging it as a core component of environmental health. PMID- 26812759 TI - Global challenges for e-waste management: the societal implications. AB - Over the last decades the electronics industry and ICT Industry in particular has revolutionized the world: electrical and electronic products have become ubiquitous in today's life around the planet. After use, those products are discarded, sometimes after re-use cycles in countries different from those where they were initially sold; becoming what is commonly called e-waste. Compared to other traditional waste streams, e-waste handling poses unique and complex challenges. e-Waste is usually regarded as a waste problem, which can cause environmental damage and severe human health consequences if not safely managed. e-Waste contains significant amounts of toxic and environmentally sensitive materials and is, thus, extremely hazardous to humans and the environment if not properly disposed of or recycled. On the other hand, e-waste is often seen as a potential source of income for individuals and entrepreneurs who aim to recover the valuable materials (metals in particular) contained in discarded equipment. Recently, for a growing number of people, in developing countries in particular, recycling and separation of e-waste has become their main source of income. In most cases, this is done informally, with no or hardly any health and safety standards, exposing workers and the surrounding neighborhoods to extensive health dangers as well as leading to substantial environmental pollution. Treatment processes of e-waste aim to remove the hazardous components and recover as much reusable material (e.g. metals, glass and plastics) as possible; achieving both objectives is most desired. The paper discuss societal implications of proper e waste management and key elements to be considered in the policy design at country level. PMID- 26812757 TI - Epidemiology of musculoskeletal injury in the California film and motion picture industry. AB - INTRODUCTION: Musculoskeletal injury exerts a significant burden on US industry. The purpose of this study was to investigate the frequency and characteristics of musculoskeletal injuries in the California (CA) film and motion picture (FMP) industry which may result in unforeseen morbidity and mortality. METHODS: We reviewed the workers' compensation (WC) claims database of the Workers' Compensation Insurance Rating Bureau of California (WCIRB) and employment statistics through the US Bureau of Labor Statistics (BLS). We analyzed the frequency, type, body part affected, and cause of musculoskeletal injuries. RESULTS: From 2003 to 2009, there were 3505 WC claims of which 94.4% were musculoskeletal. In the CA FMP industry, the most common injuries were strains (38.4%), sprains (12.2%), and fractures (11.7%). The most common sites of isolated injury were the knee (18.9%), lower back (15.0%), and ankle (8.6%). Isolated musculoskeletal spine injuries represented 19.3% of all injuries. The most common causes of injury were work-directed activity (36.0%) and falls (25.5%). CONCLUSION: We present the first report on the unique profile of musculoskeletal injury claims in the FMP industry. This data provides direction for improvement of workplace safety. PMID- 26812760 TI - Lead exposure from battery recycling in Indonesia. AB - In Indonesia, more than 200 illegal used lead acid battery (ULAB) smelters are currently operating. Only a few health studies support the finding of lead related symptoms and diseases among populations living near the smelters. To assess the blood lead levels (BLLs) and potential health impacts among the population surrounding ULAB recycling smelters, we evaluated health effects reported from 2003 to 2013, conducted focus group discussions with lead smelter owner/workers and a group of 35 female partners of smelter owners or workers not actively engaged in smelter work, and retook and measured BLLs. It was found that many children in the areas were having difficulty achieving high grades at school and having stunting or other problems with physical development. The average mean of BLLs increased by almost double in 2015, compared with in 2011. The risk of having hypertension, interference in the ability to make red blood cells in females occurred among 24% of respondents; Elevated blood pressure, hearing loss, and interference in the ability to make red bloods cell occurred in 20% of males; Kidney damage, infertility in male, nerve problems, including decreased sensation and decreased ability to move quickly occurred in 13%; Decreased ability to make red blood cells (20%), and; Frank anemia, decreased life-span, coma/seizures were experienced by 22%. The populations living in areas surrounding ULAB smelters are experiencing severe chronic health problems. It is recommended that the smelters must be moved and placed far away from the municipality. PMID- 26812761 TI - Health co-benefits in mortality avoidance from implementation of the mass rapid transit (MRT) system in Kuala Lumpur, Malaysia. AB - INTRODUCTION: The mass rapid transit (MRT) is the largest transport infrastructure project under the national key economic area (NKEA) in Malaysia. As urban rail is anticipated to be the future spine of public transport network in the Greater Kuala Lumpur city, it is important to mainstream climate change mitigation and public health benefits in the local transport development. This study quantifies the health co-benefits in terms of mortality among the urbanites when the first line of the 150 km MRT system in Kuala Lumpur commences by 2017. METHOD: Using comparative health risk assessment, we estimated the potential health co-benefits from the establishment of the MRT system. We estimated the reduced CO2 emissions and air pollution (PM2.5) exposure reduction among the general population from the reduced use of motorized vehicles. Mortality avoided from traffic incidents involving motorcycles and passenger cars, and from increased physical activity from walking while using the MRT system was also estimated. RESULTS: A total of 363,130 tonnes of CO2 emissions could be reduced annually from the modal shift from cars and motorcycles to the MRT system. Atmospheric PM2.5 concentration could be reduced 0.61 MUg/m3 annually (2%). This could avoid a total of 12 deaths, mostly from cardio-respiratory diseases among the city residents. For traffic injuries, 37 deaths could be avoided annually from motorcycle and passenger cars accidents especially among the younger age categories (aged 15-30). One additional death was attributed to pedestrian walking. The additional daily physical activity to access the MRT system could avoid 21 deaths among its riders. Most of the mortality avoided comes from cardiovascular diseases. Overall, a total of 70 deaths could be avoided annually among both the general population and the MRT users in the city. CONCLUSION: The implementation of the MRT system in Greater Kuala Lumpur could bring substantial health co-benefits to both the general population and the MRT users mainly from the avoidance of mortality from traffic injuries. PMID- 26812762 TI - How much gambling is too much? Identifying potential problem gambling among adolescents. AB - AIMS: Using a population-based sample of Finnish 12-17 year olds, this study explored gambling behaviour limits for potential problem gambling [South Oaks Gambling Screen - revised for adolescents (SOGS-RA)]. METHODS: Data were obtained from the Youth Gambling Survey 2006, which is a cross-sectional survey of a nationally representative random sample of 5000 adolescents. Adolescents who participated in gambling at least once a month were selected from the data (n=1827, 25.1% were girls). The limits for gambling behaviour were detected using receiver operating characteristic (ROC) analysis. Logistic regression was used to study associations between these behavioural limits and potential problem gambling. RESULTS: For each of the gambling behaviour indicators plotted, the risk curves showed similar trends among boys and girls. The risk of being a potential problem gambler increased noticeably with increasing gambling intensity. The ROC analysis showed that the optimal behavioural cut-off values among 12-14 year olds for frequency was gambling more than 2-3 times a month, spending more than ?2 per week on gambling, spending more than ?8 in any 1 day on gambling, and gambling on more than two different games per year. For 15-17 year olds, cut-off values were gambling more than once a week, spending more than ?4 per week and spending more than ?12 in any 1 day on gambling. Cut-off for number of game types was same as it was for younger adolescents. Of the behavioural indicators those associated with money were the most robust. CONCLUSION: Behavioural indicators can be used as initial markers of possible problem gambling. PMID- 26812763 TI - A birthday tribute to Professor Daniel TL Shek: adolescent researcher and advocate. PMID- 26812764 TI - Predictors of overweight and obesity among school going adolescents of Vadodara city in Western India. AB - BACKGROUND: Obesity among adolescents is escalating as a global epidemic which is associated with various lifestyle disorders in later life. OBJECTIVE: To assess the factors influencing overweight and obesity among school going adolescents of Vadodara city in Western India. METHODS: The study was carried out among 1050 school going adolescents from 15 schools selected by systematic random sampling after taking written informed consent from the participants. A predefined pretested semi-structured questionnaire was used to collect dietary information and physical activity. Anthropometric measurements such as height, weight, triceps skin fold thickness, waist and hip circumferences was measured using standard techniques. Adolescents were classified as overweight (>+1SD) and obese (>+2SD) with respect to their age and sex by using WHO reference charts. Factors found to be statistically significant in bivariate analysis were considered in the multiple logistic regression model. RESULTS: Among 1050 school going adolescents, 7.8% were overweight and 2.7% were obese, making the combined prevalence of overweight and obesity as 10.5%. Among socio-demographic predictors: early and mid adolescence, male gender, English medium of instruction, positive family history of obesity were found to be the significantly associated with overweight/obesity among the study population. Whereas consumption of outside food, meal skipping habit, infrequent consumption of staple healthy food items were found to be significant diet related predictor variables for overweight/obesity. Among the physical activity predictors: sedentary activities, less outdoor games and sleep deprivation were also found to be significant predictors of overweight/obesity. CONCLUSION: Adolescents should be motivated to take adequate amount of healthy staple food like dal-rice at home and to engage in outdoor sports related activity to prevent overweight and obesity. PMID- 26812765 TI - Effectiveness of group CBT in treating adolescents with depression symptoms: a critical review. AB - Depression is among the most common psychological disorders of adolescents. Its management is based on pharmacological treatment, psychological therapy, or a combination thereof. Cognitive behavioral therapy (CBT) is the most extensively tested intervention for adolescent depression. A PubMed search was conducted for randomized controlled trials (RCT) of the efficacy of CBT in treating adolescents with depressive symptoms published in 2005-2015. Keywords were "cognitive behavioral therapy", "group therapy", "depression" and "adolescent". Of the 23 papers that were retrieved, only six met all inclusion criteria. Three of them reported a significant reduction in depressive symptom severity after either individual or group (G)-CBT compared with the control group, even with a small number of CBT sessions (six rather than 10-12), with a medium or medium-to-large effect size. One study reported improved self-awareness and a significantly greater increase in perceived friend social support compared with bibliotherapy and check with brochure. Two studies reported clinical symptom reduction without significant differences compared with the control group (activity contrast). This review highlighted primarily that very few RCT have applied CBT in adolescents; moreover, it confirmed the effectiveness of G-CBT, especially as psychotherapy, although it was not always superior to other interventions (e.g. other activities in prevention programs). Comparison showed that G-CBT and group interpersonal psychotherapy were both effective in reducing depressive symptoms. Successful G CBT outcomes were related to the presence of peers, who were an important source of feedback and support to observe, learn, and practice new skills to manage depressive symptoms and improve social-relational skills. PMID- 26812766 TI - An evaluation of Gaelic Athletic Association (GAA) athletes' self-reported practice of playing while concussed, knowledge about and attitudes towards sports related concussion. AB - BACKGROUND/AIM: Sports-related concussions are now recognized as a major public health concern. However, despite the association of concussion with short- and long-term health consequences, many young athletes still lack basic knowledge about concussion and seem to believe that concussions may be "toughed out" and do not require medical attention. This study assessed self-reported practice of playing in training or a match while concussed among Gaelic Athletic Association (GAA) athletes in Ireland aged 13-25 years old (M=19.19, SD=3.54). This study also assessed knowledge about and attitudes towards sports-related concussion in GAA players in Ireland. METHODS: Using a self-report questionnaire, data were captured electronically on GAA athletes aged 13-25 years old (n=80) regarding knowledge about the detection, assessment and management of sports-related concussion, as well as participant's attitudes towards concussion and self reported practice of playing in training or a match while concussed. Data were collected from June to August 2013. RESULTS: This study revealed that approximately one in four athletes reported having played while concussed in practice or during a match. Males were significantly more likely to play while concussed than females (40.9% and 17.2%, respectively). Results from this study indicated participants lack a complete understanding of concussion, as common misconceptions about concussion prevailed. Analyses revealed that participants generally have safe attitudes towards concussion and concussion management. CONCLUSION: Generating awareness of the potential short- and long-term health consequences of concussion, coupled with the promotion of safer attitudes towards this injury, could minimize the number of players who return-to-play pre-maturely and promote a more safety-conscious sports culture in Ireland. PMID- 26812767 TI - Exploring the relationship difficulties of Iranian adolescents with conduct disorder: a qualitative content analysis. AB - BACKGROUND: Conduct disorder is characterized by aggressive behaviors, deceitfulness or theft, destruction of property and serious violations of rules prior to age 18 years. The object relations theory provides an integrative model to understand the problems of conduct disorder, and proposes that child-caregiver relationships develop the internal working models of self and others. The aim of this study was to explore the relationship difficulties of Iranian adolescents with conduct disorder. METHODS: This study was a qualitative directed content analysis research. The in-depth interview was conducted with nine male adolescents aged 12-17 years who had conduct disorder with or without substance use disorder at the reformatory in Tehran. All tape-recorded data were fully transcribed and analyzed. RESULTS: The relations with different objects including parents, siblings, relatives, friends, peers, teachers, other school members, colleagues and employers were analyzed, and four themes were extracted: 1) Object relations based on insecurity and fear; 2) Object relations based on inability and abjection; 3) Object relations based on pessimism and mistrust; 4) Object relations based on non-maintenance of boundaries and limits. CONCLUSION: The importance of object relations and attachment problems in adolescents with conduct disorder, and their need to participate in special intervention programs should be reconsidered. PMID- 26812768 TI - Adolescents' sexual and reproductive health: an ecological perspective. AB - BACKGROUND: Adolescence is the key time in the formation of sexual confidence and fertility in people and many risky sexual behaviors in this sensitive era are the roots of many adulthood diseases. STD and early pregnancy are among the most important issues of adolescence. OBJECTIVE: This study deals with reviewing ecological factors related to the sexual and reproductive health of adolescents. METHODS: As this study was a narrative review the researchers conducted their computer search in public bases such as Google Scholar and then in more specialized ones such as MEDLINE, EMBASE, Science Direct, Up-to-date, SPRINGER, SID, Magi ran, Iranmedex and Irandoc with the key words adolescents, sexual health, reproductive health and ecological from 1991 to 2015. Initially 152 articles were elicited and after a review study of the title and abstract, 80 articles entered the study. After reading the full text, 39 articles were chosen for writing the current review article. RESULTS: Reviewing the articles led to organizing the contents in three main classes according to Bronfenbrenner's suggestion namely ecological factors at microsystem, mesosystem and macrosystem levels which include individual predisposing factors, environmental enabling factors and social reinforcing factors. CONCLUSION: Adolescents are at a high risk of STD and early pregnancy. Many factors are considered as effective at this critical era, based on which comprehensive intervention based on ecological factors is needed to step forward toward preventing adolescence risks. PMID- 26812769 TI - The winner takes it all? Characteristics of adolescent at-risk/problem gamblers in Switzerland. AB - BACKGROUND: Gambling has and still entertains people in almost all societies throughout the world. Western societies have faced considerable changes in the amount and accessibility of gambling possibilities during the last decades, and the rates of both adolescent gamblers and problem gamblers have increased significantly. OBJECTIVE: To determine the characteristics of at-risk and problem adolescent gamblers in Switzerland. SUBJECTS: The study population consisted of 3134 students (1669 females) attending post-mandatory education in 15 randomly chosen centres. Participants were divided into non- (n=2207), non-problematic (n=754) and at-risk/ problematic gamblers (n=176). METHODS: Both gambling groups were compared to non-gamblers on socio-demographic measures, substance use and Internet use. Overall, 29.6% had gambled during the past year and 5.6% had gambled in a risky or problematic way. Compared to non-gamblers and after controlling for potential confounders, non-problem gamblers were significantly more likely to be male, apprentices and to misuse alcohol. At-risk/problematic gamblers were additionally more likely to smoke cannabis, to be problematic Internet users and to be non-Swiss than non-gamblers. CONCLUSION: At-risk and problematic adolescent gambling is associated with other health risk behaviours. Health practitioners should include gambling in the psycho-social screening and preventive counselling of adolescents. PMID- 26812770 TI - The first cigarette and then.......... PMID- 26812771 TI - Long-term first line medical treatment in a 4-year-old girl with Xq26.3 microduplication-negative somatotropinoma. Case report and literature review. AB - Growth hormone (GH) secreting adenoma represents a therapeutic challenge in childhood. Because of its rarity no treatment guidelines are available and pediatric management often results from recommendations issued for adults. We report a case of a 4-year-old girl with somatotropinoma successfully treated with only medical treatment. She presented with tall stature and history of growth acceleration. Imaging and laboratory confirmed the diagnosis of GH secreting macroadenoma. She started medical treatment with a somatostatin analogue and a dopamine agonist. During an 8-year follow-up period, a good clinical control of the disease and a shrinkage of the adenoma have been demonstrated. At the last observation she achieved normal near-adult height and pubertal development. According to our experience and limited literature evidences, first line treatment with somatostatin analogues can be attempted in patients with somatotropinoma. This approach seems to be able to control the clinical course of the disease, allowing to postpone transphenoidal surgery to adult age or to avoid it. PMID- 26812772 TI - The association of thyroid hormones and blood pressure in euthyroid preadolescents. AB - BACKGROUND: Hypertension is the leading cause of cardiovascular disease worldwide, and both high and low blood pressures are associated with various chronic diseases. Thyroid hormones have profound effects on cardiovascular function, including on blood pressure. Recent studies have shown that childhood hypertension can lead to adult hypertension. Therefore, adequate blood pressure control is important from early life. Employing a life-course approach, we aimed to investigate the association between thyroid hormones and blood pressure in children. METHODS: A total of 290 children from the Ewha Woman's University Hospital birth cohort participated in a preadolescent check-up program. We assessed the levels of serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) and the blood pressure status in these children. Thyroid hormone concentrations were measured using an electro-chemiluminescence immunoassay (ECLIA), and hypertension was defined according to the guideline of the Korea Centers for Disease Control and Prevention. RESULTS: The sex-, age-, and height adjusted prevalence of hypertension was 27.0% in the present study. On regression analysis, serum FT4 showed significantly negative association with diastolic blood pressure (DBP; beta=-8.24, 95% CI: -14.19-2.28, p=0.007). However, these relationships were not significant after adjustment for sex, age, and current body mass index. The levels of serum TSH showed no relationship with mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) after adjustment. No significant differences in serum TSH and FT4 levels according to hypertension status were found. CONCLUSIONS: These findings suggest that thyroid hormone is not independently associated with increased blood pressure in euthyroid preadolescents. PMID- 26812773 TI - Pubertal outcome in a female with virilizing adrenocortical carcinoma. AB - Adrenocortical tumors are neoplasms that rarely occur in pediatric patients. Adrenocortical carcinoma (ACC) is even more uncommon, and is an aggressive malignancy with 5-year survival of 55% in a registry series. There is a lack of information on long-term endocrine outcome in survivors. We describe a 10-year follow-up in a patient who presented at 3 years 5 months with a 1-year history of axillary odor and 6 months' history of pubic hair development with an increased clitoral size. Androgen levels were increased and a pelvic sonogram revealed a suprarenal mass of the left kidney. The tumor was successfully removed. At 6 years 11 months, androgen levels increased again. Workup for tumor recurrence was negative and the findings likely represented early adrenarche. The patient had menarche at an appropriate time and attained a height appropriate for her family. PMID- 26812774 TI - Absence of a relationship between thyroid hormones and vitamin D levels. AB - BACKGROUND: Vitamin D is an immune modulator that may play a role in thyroid related autoimmunity. METHODS: We analyzed a US population based dataset to determine the relationship between serum 25-hydroxyvitamin D (25OHD) and thyroid hormones while assessing the effects of autoimmunity and BMI. RESULTS: 25OHD did not correlate significantly with any thyroid related measure. 25OHD levels stratified by thyroid antibody status were not statistically different between antibody positive and negative groups. The mean 25OHD levels of lean, overweight, and obese groups defined by BMI were lower than those of the normal group. Only the mean thyroid stimulating hormone (TSH) value in the obese group was significantly higher than the normal group. CONCLUSIONS: We conclude that thyroid related measures and 25OHD serum levels are not related. PMID- 26812775 TI - Relationship between oxidative stress and blood glucose fluctuations evaluated with daily glucose monitoring in children with type 1 diabetes mellitus. AB - BACKGROUND: The aim of this study is to determine the relationship between oxidative stress marker (8-iso-prostaglandine F2alpha) and glycemic indices computed from daily glucose monitoring data in children with type 1 diabetes mellitus (T1DM). METHODS: Thirty-one children and adolescents with T1DM (median age 12.2 years) and healthy subjects (median age 11.7 years) were enrolled into the study. Anthropometric data were recorded for the entire group before the study. In addition, diabetes duration, insulin requirement, lipid values, microalbuminuria, HbA1c were recorded in T1DM subjects. T1DM subjects performed self-monitoring of blood glucose (SMBG) for a month (at least four times a day) for calculating glycemic indices. Twenty-four-hour urine 8-iso-prostoglandine F2alpha levels were studied at the end of the study period in the both groups. RESULTS: Median diabetes duration was 5 years, hemoglobin A1c (HbA1c) was 7.3%. Standard deviation (SD) of the blood glucose (BG) was determined as 85 mg/dL. Median urinary 8-iso-prostoglandine F2alpha was found to be significantly higher than that of the healthy subjects (2808.9 and 298 pg/mg creatinine, p<0.001, respectively). There was no correlation between urinary 8-iso-prostoglandine F2alpha and age, anthropometric data, diabetes duration, insulin requirement, lipid values, microalbuminuria, HbA1c, or SD of BG in T1DM groups. CONCLUSIONS: This study showed that, 8-iso-prostoglandine F2alpha that is an oxidative stress marker, is significantly higher in T1DM than that of healthy subjects while, no significant relation between glycemic indices and urinary 8-iso-prostoglandine F2alpha levels were demonstrated. Further studies are needed to assess other factors, and the relationship between glucose fluctuations and oxidative stress markers. PMID- 26812776 TI - Growth failure in adolescents: etiology, the role of pubertal timing and most useful criteria for diagnostic workup. AB - BACKGROUND: The aim of the study was to evaluate the etiology, the role of pubertal timing and most useful criteria for diagnostic workup in adolescents with growth failure. METHODS: Adolescents (n=182) aged 10.0-18.0 years underwent a standardized diagnostic protocol. Constitutional delay of growth and puberty (CDGP) was defined as late pubertal onset or a Tanner stage less than -2 SDS. Dutch and Finnish criteria for growth monitoring were retrospectively assessed. RESULTS: In 13 children (7.1%) a specific diagnosis could be established. CDGP was diagnosed in 10% of patients aged >=13 (girls) or >=14 years (boys). Sensitivity to detect pathologic causes was 85% and 62% for, respectively Dutch and Finnish criteria for growth monitoring as used in younger children, but specificity was low (55%-59%). CONCLUSIONS: In adolescents, pathological causes for growth failure and pubertal delay are common, and we recommend a combination of height SDS, distance to THSDS and growth deflection for deciding on further diagnostic testing. PMID- 26812777 TI - Resistance to thyroid hormone alpha, revelation of basic study to clinical consequences. AB - In the past 3 years, 15 patients with resistance to thyroid hormone alpha (RTHalpha), nine THRA gene mutations have been reported, reforming classification of RTH. RTHalpha exhibits distinguished clinical manifestations from RTHbeta, including growth retardation, skeletal dysplasia, impaired neurodevelopment, cardiovascular dysfunction, constipation and specific thyroid axis type. This review focuses on possible pathogenesis by revelatory basic science of RTHalpha animal models in vivo, and patients' mutant thyroid hormone receptor alpha (TRalpha) in vitro. Clinical manifestations and L-T4 effects are summarized, showing strong correlation to the severity of mutation mostly within the domain which dominated TR interaction with T3 and its corepressors/coactivators. In particular, we propose the diagnosis clues and promising treatment for clinicians. PMID- 26812778 TI - Slipped capital femoral epiphysis and associated hypothyroidism. A review of the literature with two classic case examples. AB - Slipped capital femoral epiphysis (SCFE) is a relatively common hip disorder often seen in overweight, peripubertal children. Although the exact etiology is uncertain, it is generally accepted that underlying endocrinopathies play a role in the pathogenesis. Hypothyroidism is the endocrine disorder cited most commonly in association with SCFE, and patients often have no history of thyroid dysfunction at the time of presentation. Despite being a well-recognized risk factor, recommendations for screening thyroid function in patients with typical presentations of SCFE have not been deemed cost-effective; however, there is data to support screening for hypothyroidism in patients with atypical presentations of SCFE or short stature. Hypothyroidism may have a significant impact on healing and bone union after surgical management of SCFE and there is a paucity of case reports in the literature describing potential peri- and postoperative complications. We performed a systematic review of the literature of all reported cases of SCFE with associated hypothyroidism using the search terms, which demonstrated a physiologic relationship between hypothyroidism and SCFE. Two case reports of SCFE in patients with hypothyroidism and associated complications are presented with the literature review. There is a physiologic relationship between thyroid dysfunction and SCFE, and we postulate that profound hypothyroidism may contribute to delayed healing or nonunion in patients undergoing operative management. We support the recommendation to screen patients with short stature, atypical presentation of SCFE, or perisistent nonunion after surgery. In cases of hypothyroidism, we recommend thyroid hormone replacement and laboratory confirmation of return to euthyroid state prior to operative intervention. PMID- 26812779 TI - New approach to phenotypic variability and karyotype-phenotype correlation in Turner syndrome. AB - BACKGROUND: Phenotypic variability of Turner syndrome (TS) challenges clinicians, and undiagnosed mosaicism may lead to conflicting results of karyotype-phenotype correlations. This study assessed the extent of phenotypic variability and investigated the presence of karyotype-phenotype correlations. METHODS: The sample comprised 80 patients with >=50 cells analyzed in karyotype. Twenty were 45,X/46,X,+mar; three groups of 20 patients were constructed by matching those girls with the nearest-aged patient with 45,X, 45,X/46,XX and 45,X/46,X,i(Xq) or 46,X,i(Xq) karyotype. RESULTS: Data were obtained on height z-score, dysmorphic features, echocardiogram and urinary system sonography. The number of dysmorphic features ranged from one to 16 and was not correlated to age at diagnosis or height. The groups did not differ in height, number of dysmorphic features, cardiovascular and urinary system anomalies and frequency of any specific feature, except for short fourth metacarpal. CONCLUSIONS: Wide phenotypical variability of TS may be objectively described and its clinical picture is not correlated to karyotype. PMID- 26812780 TI - Emotion regulation strategies in trauma-related disorders: pathways linking neurobiology and clinical manifestations. AB - Emotion regulation impairments with traumatic origins have mainly been studied from posttraumatic stress disorder (PTSD) models by studying cases of adult onset and single-incident trauma exposure. The effects of adverse traumatic experiences, however, go beyond the PTSD. Different authors have proposed that PTSD, borderline personality, dissociative, conversive and somatoform disorders constitute a full spectrum of trauma-related conditions. Therefore, a comprehensive review of the neurobiological findings covering this posttraumatic spectrum is needed in order to develop an all-encompassing model for trauma related disorders with emotion regulation at its center. The present review has sought to link neurobiology findings concerning cortico-limbic function to the field of emotion regulation. In so doing, trauma-related disorders have been placed in a continuum between under- and over-regulation of affect strategies. Under-regulation of affect was predominant in borderline personality disorder, PTSD with re-experiencing symptoms and positive psychoform and somatoform dissociative symptoms. Over-regulation of affect was more prevalent in somatoform disorders and pathologies characterized by negative psychoform and somatoform symptoms. Throughout this continuum, different combinations between under- and over-regulation of affect strategies were also found. PMID- 26812781 TI - Recent progress on the role of GABAergic neurotransmission in the pathogenesis of Alzheimer's disease. AB - Despite their possible causative role, targeting amyloidosis, tau phosphorylation, acetylcholine esterase, glutamate, oxidative stress and mitochondrial metabolism have not yet led to the development of drugs to cure Alzheimer's disease (AD). Recent preclinical and clinical reports exhibit a surge in interest in the role of GABAergic neurotransmission in the pathogenesis of AD. The interaction among GABAergic signaling, amyloid-beta and acetylcholine is shown to affect the homeostasis between excitation (glutamate) and inhibition (GABA) in the brain. As a consequence, over-excitation leads to neurodegeneration (excitotoxicity) and impairment in the higher level functions. Previously, the glutamate arm of this balance received the most attention. Recent literature suggests that over-excitation is primarily mediated by dysfunctional GABA signaling and can possibly be restored by rectifying anomalous metabolism observed in the GABAergic neurons during AD. Additionally, neurogenesis and synaptogenesis have also been linked with GABAergic signaling. This association may provide a basis for the needed repair mechanism. Furthermore, several preclinical interventional studies revealed that targeting various GABA receptor subtypes holds potential in overcoming the memory deficits associated with AD. In conclusion, the recent scientific literature suggests that GABAergic signaling presents itself as a promising target for anti-AD drug development. PMID- 26812782 TI - Remote ischemic conditioning for acute ischemic stroke: dawn in the darkness. AB - Stroke is a leading cause of disability with high morbidity and mortality worldwide. Of all strokes, 87% are ischemic. The only approved treatments for acute ischemic stroke are intravenous thrombolysis with alteplase within 4.5 h and thrombectomy within 8 h after symptom onset, which can be applied to just a few patients. During the past decades, ischemic preconditioning has been widely studied to confirm its neuroprotection against subsequent ischemia/reperfusion injury in the brain, including preconditioning in situ or in a remote organ (such as a limb) before onset of brain ischemia, the latter of which is termed as remote ischemic preconditioning. Because acute stroke is unpredicted, ischemic preconditioning is actually not suitable for clinical application. So remote ischemic conditioning performed during or after the ischemic duration of the brain was then designed to study its neuroprotection alone or in combination with alteplase in animals and patients, which is named as remote ischemic perconditioning or remote ischemic postconditioning. As expected, animal experiments and clinical trials both showed exciting results, indicating that an evolution in the treatment for acute ischemic stroke may not be far away. However, some problems or disputes still exist. This review summarizes the research progress and unresolved issues of remote ischemic conditioning (pre-, per-, and post-conditioning) in treating acute ischemic stroke, with the hope of advancing our understanding of this promising neuroprotective strategy for ischemic stroke in the near future. PMID- 26812783 TI - Aqueous extracts of avocado pear (Persea americana Mill.) leaves and seeds exhibit anti-cholinesterases and antioxidant activities in vitro. AB - BACKGROUND: Avocado pear (Persea americana Mill.) leaves and seeds are used in traditional medicine for the treatment/management of Alzheimer disease (AD); however, information on the mechanism of actions is limited. This study sought to investigate the effect of P. americana leaf and seed aqueous extracts on some enzymes linked with AD (acetylcholinesterase [AChE] and butyrylcholinesterase [BChE] activities) and their antioxidant potentials in vitro. METHODS: The inhibitory effects of extracts on AChE and BChE activities and antioxidant potentials (inhibition of Fe2+- and sodium nitroprusside-induced thiobarbiturate reactive species [TBARS] production in rat brain homogenates, radicals [1,1 diphenyl-2-picrylhydrazyl, hydroxyl, and nitric oxide] scavenging and iron [Fe] chelation abilities) were investigated. Phenolic content and phytochemical screening were carried out. Alkaloid profile was also determined using gas chromatography coupled with flame ionization detector (GC-FID). RESULTS: The extracts inhibited AChE and BChE activities and prooxidant-induced TBARS production in a dose-dependent manner, with the seed extract having the highest inhibitory effect and the leaf extract exhibiting higher phenolic content and radical scavenging abilities, but lower Fe chelation ability compared with that of the seed. The phytochemical screening revealed the presence of saponins, alkaloids, and terpenoids in both extracts, whereas the total alkaloid profile was higher in the seed extract than in the leaf extract, as revealed by GC-FID. CONCLUSIONS: The anti-cholinesterase and antioxidant activities of avocado leaf and seed could be linked to their phytoconstituents and might be the possible mechanisms underlying their use as a cheap and natural treatment/management of AD. However, these extracts should be further investigated in vivo. PMID- 26812784 TI - Antinociceptive and anti-inflammatory potentials of kolaviron: mechanisms of action. AB - BACKGROUND: Major attention has been on dietary and medicinal phytochemicals that inhibit or reverse abnormal conditions caused by nociceptive and inflammatory stimuli. Garcinia kola (Guttiferae) seed, known as "bitter kola", plays an important role in African ethno-medicine and traditional hospitality like in the treatment of inflammation, colds, bronchitis, bacterial, and viral infections. A number of useful phytochemicals have been isolated from the seed, and the most prominent of them is kolaviron (Garcinia bioflavonoid), which has been suggested to have antinociceptive and anti-inflammatory potentials. The aim of this experiment is to explore the mechanisms of action of the antinociceptive and anti inflammatory potentials of kolaviron. METHODS: The probable mechanisms of action of kolaviron were assessed by using naloxone, prazosin, and atropine to investigate the involvement of adrenergic, opioidergic, and cholinergic systems, respectively, using tail flick, the acetic acid-induced writhing, formalin induced paw licking, and carrageenan-induced paw edema models. Also, hematoxylin and eosin (H&E) staining was used to analyze the level of inflammation. RESULTS: In the acetic acid-induced writhing test in mice, pretreatment with naloxone, prazosin, and atropine significantly reversed the antinociception effects of kolaviron (200 mg/kg) when compared with control and kolaviron groups. In the formalin-induced paw licking test in mice, there was a significant decrease on the antinociceptive effects of kolaviron in the late phase when compared with the control, while the pretreatment with naloxone and prazosin significantly reversed the antinociception of kolaviron but atropine did not have any significant decrease when compared with the kolaviron group. In the tail flick latency assay in rats, pretreatment with naloxone and prazosin significantly reversed the antinociception of kolaviron but atropine; however, did not have any significant increase when compared with the control and kolaviron groups. The result of the study also shows a highly significant inhibition of paw edema in the carrageenan induced receiving kolaviron when compared with the vehicle carrageenan-induced groups. Histological staining also showed that kolaviron significantly reduced the infiltration of inflammatory cells in the paw tissues. CONCLUSIONS: Kolaviron possesses antinociceptive and anti-inflammatory activity, both centrally and peripherally, which justifies its folkloric use to relieve pain and inflammation. It may be exerting its effects through mechanisms that involve opioidergic and adrenergic systems, and may not involve the cholinergic system. PMID- 26812785 TI - Can genotype determine the sports phenotype? A paradigm shift in sports medicine. AB - In last two decades, there has been an evolution in sports medicine. Several researchers have worked on different domains of sports medicine, like strength, endurance, sports injury, and psychology. Besides this, several groups have explored the changes at cellular and molecular levels during exercise, which has led to the development of the new domain in sports science known as genetic medicine. Genetic medicine deals with the genotypic basis of sports phenotype. In this article, we try to provide an up-to-date review on genetic determinants of sports performance, which will be like a journey from the nostalgic past towards the traditional present and the romantic future of sports medicine. Endurance and power performance are two important domains of athletes. They vary in individuals, even among trained athletes. Researches indicate that the genetic makeup of sportsmen play a vital role in their performance. Several genetic factors are reported to be responsible for endurance, power, susceptibility to injury, and even psychology of the individual. Besides this, proper training, nutrition, and environment are also important in shaping their potential. The aim of this discussion is to understand the influence of the environment and the genetic makeup on the performance of the athletes. There is sufficient evidence to suggest that genotype determines the sports phenotype in an athlete. Choosing the right sports activity based on genetic endowment is the key for achieving excellence in sports. PMID- 26812786 TI - Efficacy of oral vs. intratympanic corticosteroids in sudden sensorineural hearing loss. AB - BACKGROUND: The current standard treatment for sudden sensorineural hearing loss (SSNHL) comprises of tapered course of oral corticosteroids. Intratympanic steroids are introduced as another modality of treatment, but management of SSNHL continues to be debatable. The present study was designed to evaluate the efficacy of steroids given orally and by the intratympanic route. METHODS: A prospective, randomized, open-labeled study was conducted involving 42 patients. These were randomly divided into two groups; group I patients received oral prednisone tapered over 14 days, and group II patients were treated with intratympanic methylprednisolone (40 mg/mL). One milliliter of the drug solution containing 40 mg of the drug (40 mg/mL) was injected into the middle ear cavity through the trans-tympanic route. The drug was injected twice a week for 2 weeks. The total duration of the study was 60 days, and hearing outcome was assessed on the basis of change in pure tone average. RESULTS: An improvement of 18.24+/-8.72 dB was recorded in group I patients treated with oral prednisone in comparison to 14.68+/-12.88 dB improvement in group II. Statistically significant improvement in hearing was observed in both groups, but it was not significant when group I and group II were compared. CONCLUSIONS: The post-treatment outcomes among patients who receive either oral prednisone or intratympanic methylprednisolone within 2 weeks of onset of symptoms were comparable. The outcomes were affected by degree of hearing loss and association of SSNHL with vertigo. PMID- 26812787 TI - Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function. AB - The nuclear factor erythroid-derived 2 (NF-E2)-related factor 2 (Nrf2) is a transcription factor well-known for its function in controlling the basal and inducible expression of a variety of antioxidant and detoxifying enzymes. As part of its cytoprotective activity, increasing evidence supports its role in metabolism and mitochondrial bioenergetics and function. Neurodegenerative diseases are excellent candidates for Nrf2-targeted treatments. Most neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia and Friedreich's ataxia are characterized by oxidative stress, misfolded protein aggregates, and chronic inflammation, the common targets of Nrf2 therapeutic strategies. Together with them, mitochondrial dysfunction is implicated in the pathogenesis of most neurodegenerative disorders. The recently recognized ability of Nrf2 to regulate intermediary metabolism and mitochondrial function makes Nrf2 activation an attractive and comprehensive strategy for the treatment of neurodegenerative disorders. This review aims to focus on the potential therapeutic role of Nrf2 activation in neurodegeneration, with special emphasis on mitochondrial bioenergetics and function, metabolism and the role of transporters, all of which collectively contribute to the cytoprotective activity of this transcription factor. PMID- 26812788 TI - Highlight: Perspectives of molecular neuroscience in health and disease. PMID- 26812789 TI - Effect of molecular chaperones on aberrant protein oligomers in vitro: super versus sub-stoichiometric chaperone concentrations. AB - Living systems protect themselves from aberrant proteins by a network of chaperones. We have tested in vitro the effects of different concentrations, ranging from 0 to 16 MUm, of two molecular chaperones, namely alphaB-crystallin and clusterin, and an engineered monomeric variant of transthyretin (M-TTR), on the morphology and cytotoxicity of preformed toxic oligomers of HypF-N, which represent a useful model of misfolded protein aggregates. Using atomic force microscopy imaging and static light scattering analysis, all were found to bind HypF-N oligomers and increase the size of the aggregates, to an extent that correlates with chaperone concentration. SDS-PAGE profiles have shown that the large aggregates were predominantly composed of the HypF-N protein. ANS fluorescence measurements show that the chaperone-induced clustering of HypF-N oligomers does not change the overall solvent exposure of hydrophobic residues on the surface of the oligomers. alphaB-crystallin, clusterin and M-TTR can diminish the cytotoxic effects of the HypF-N oligomers at all chaperone concentration, as demonstrated by MTT reduction and Ca2+ influx measurements. The observation that the protective effect is primarily at all concentrations of chaperones, both when the increase in HypF-N aggregate size is minimal and large, emphasizes the efficiency and versatility of these protein molecules. PMID- 26812790 TI - MicroRNA regulation of airway smooth muscle function. AB - Airway smooth muscle (ASM) controls airway narrowing and plays a pivotal role in the pathogenesis of asthma. MicroRNAs are small yet powerful gene tuners that regulate diverse cellular processes. Recent studies have demonstrated the versatile role of microRNAs in regulating multiple ASM phenotypes that are critically involved in asthma pathogenesis. These ASM phenotypes include proliferation, cell size, chemokine secretion, and contractility. Here we review microRNA-mediated regulation of ASM functions and discuss the potential of microRNAs as a novel class of therapeutic targets to improve ASM function for asthma therapy. PMID- 26812791 TI - Laboratory and clinical risk assessment to treat myelodysplatic syndromes. AB - Myelodisplastic syndromes (MDS) are heterogeneous myeloid disorders characterized by peripheral cytopenias and increased risk of transformation into acute myelogenous leukemia (AML). MDS are generally suspected in the presence of cytopenia on routine analysis and the evaluation of bone marrow cells morphology and cellularity leads to correct diagnosis of MDS. The incidence of MDS is approximately five cases per 100,000 people per year in the general population, but it increases up to 50 cases per 100,000 people per year after 60 years of age. Typically MDS affect the elderly, with a median age at diagnosis of 65-70 years. Here the current therapeutic approaches for MDS are evaluated by searching the PubMed database. Establishing the prognosis in MDS patients is a key element of therapy. In fact an accurate estimate of prognosis drives decisions about the choice and timing of the therapeutic options. Therapy is selected based on prognostic risk assessment, cytogenetic pattern, transfusion needs and biological characteristics of the disease, comorbidities and clinical condition of the patients. In lower-risk patients the goals of therapy are different from those in higher-risk patients. In lower-risk patients, the aim of therapy is to reduce transfusion needs and transformation to higher risk disease or AML, improving the quality of life and survival. In higher-risk patients, the main goal of therapy is to prolong survival and to reduce the risk of AML transformation. Current therapies include growth factor support, lenalidomide, immunomodulatory and hypomethylating agents, intensive chemotherapy, and allogenic stem cell transplantation. The challenge when dealing with MDS patients is to select the optimal treatment by balancing efficacy and toxicity. PMID- 26812792 TI - Free light chain testing for the diagnosis, monitoring and prognostication of AL amyloidosis. AB - The disease causing agent in systemic AL amyloidosis is a monoclonal immunoglobulin free light chain, or fragments thereof, circulating in the blood. It is not surprising, therefore, that measurement of serum free light chains plays a central role in the management of this disorder. In this paper, we review the utility of the serum free light chain assay in the investigation, prognostication and monitoring of AL amyloidosis. Data on the two currently available commercial assays is compared and some practical applications of the assay's use are presented. While there are limitations, it is clear that the availability of the free light chain assay in the laboratory is a major advance and plays an essential role in the management of patients with AL amyloidosis. PMID- 26812793 TI - Updating pregnancy diabetes guidelines: is (y)our laboratory ready? PMID- 26812794 TI - Discriminant indices for distinguishing thalassemia and iron deficiency in patients with microcytic anemia. PMID- 26812795 TI - Quantification of beta region IgA paraproteins - should we include immunochemical "heavy/light chain" measurements? Counterpoint. AB - Serum protein electrophoresis (SPE), serum immunofixation (s-IFE), free light chain measurement (FLC) and nephelometric measurements of total immunoglobulin in serum (IgTot) are some of the laboratory tests required for the management of plasma cell proliferative disorders. The monoclonal protein is usually visible on SPE as a spike (M-spike) in the gamma region and the derived densitogram is used to quantify it relative to serum total protein concentration. IgA M-protein, however, often migrates in the beta region on SPE and its quantification can be masked by other serum proteins that migrate in this region. The immunoassay HevyliteTM (heavy/light chain, HLC) seems to solve this problem: it quantifies the involved/uninvolved isotype, calculating the ratio IgAkappa/IgAlambda, considered indicative of clonal proliferation. However, this test seems redundant in the case of artifacts on SPE such as obvious hemolysis or lipemia, or if the IgA M-spike is clearly visible in the beta region. In conclusion whereas the IgA HLC assay does not represent an alternative to SPE and s-IFE in the diagnostic patient workup, it may prove to be an alternative to SPE, s-IFE and total IgA quantification in risk stratification and evaluation of response to therapy in patients affected by MM and other monoclonal plasma proliferative disorders. PMID- 26812796 TI - Is the combination of trueness and precision in one expression meaningful? On the use of total error and uncertainty in clinical chemistry. AB - The performance of all measurement procedures used in routine clinical laboratories shall be verified; a minimum is to verify the precision and trueness of the results. This is well established and adequate recommendations and procedures are available. Conveying this information in a form that is adequate and understandable for the practical end-user in the health care sector is still a much debated issue. By tradition, since several decades, the "total error" (TE) is presented, a quantity that is the linear sum of an imprecision and bias. Since any combination of the two can yield the same TE it may not be very helpful in finding and correcting a root-cause for an unacceptable value. Also, an acceptable TE may hide an unacceptable level of its constituents. An alternative is the measurement uncertainty (MU), which is recommended by accreditation and standardizing bodies The MU separates the imprecision and bias and expresses an interval around a best estimate within which the true value is expected with a certain probability. We describe the reporting the best estimate of a measurement result and describe how the uncertainty of the result, can be calculated, using simple custom-made software. PMID- 26812797 TI - Patient-performed extraction of faecal calprotectin. AB - BACKGROUND: Faecal (f-) calprotectin is a widely used marker for intestinal inflammation. However, extraction procedure is time consuming and cumbersome. The main aim of this study was to evaluate patient-performed extraction of f calprotectin compared to extraction performed in the laboratory. METHODS: A total of 81 adult patients with an established diagnosis of inflammatory bowel disease provided two samples from the same bowel movement, one conventional faeces sample and one sample with a patient administered extraction device. A laboratory technician extracted the conventional faeces sample with the same extraction device. RESULTS: F-calprotectin results from the laboratory-performed extraction and the patient-performed extraction correlated significantly, with a Spearman rank correlation coefficient of 0.92. Method comparison showed a slope of 1.20 (95% confidence interval 1.08-1.36) with intercept of -0.30 (95% confidence interval -9.00 to 4.62). This demonstrates a small proportional difference between the results from the home extracted samples and the results from the laboratory extracted samples, where the home extracted samples are slightly higher. However, six of the 81 patients had made obvious mistakes in the extraction process and their samples were excluded from the study. CONCLUSIONS: Patient administered extraction of f-calprotectin can be a realistic alternative for selected patients. However, instructions must be very precise to avoid mistakes. PMID- 26812798 TI - Earlier detection of sepsis by Candida parapsilosis using three-dimensional cytographic anomalies on the Mindray BC-6800 hematological analyzer. PMID- 26812799 TI - Discriminant indices for distinguishing thalassemia and iron deficiency in patients with microcytic anemia: a reply. PMID- 26812800 TI - Dydrogesterone and pre-term birth. AB - Progestin supplementation appears to be a promising approach to both preventing initiation of pre-term labor and treating it once it is already established. Successful pregnancy depends on maternal tolerance of the fetal "semi-allograft". A protein called progesterone-induced blocking factor (PIBF), by inducing a Th2 dominant cytokine production mediates the immunological effects of progesterone. Over time, various attempts have been made to clarify the question, whether progestogens can contribute positively to either prevention or treatment of pre term labor and birth. Dydrogesterone treatment of women at risk of pre-term delivery results in increased PIBF production and IL-10 concentrations, and lower concentrations of IFNgamma and could be effective for prevention or treatment of pre-term labor. Further randomized studies are needed. PMID- 26812801 TI - Prenatal exposure to bisphenol A alters mouse fetal pancreatic morphology and islet composition. AB - BACKGROUND: Exposure to bisphenol A (BPA), an endocrine disrupting chemical, during gestation is associated with a variety of metabolic dysfunctions in adulthood, including hyperinsulinemia, glucose intolerance and insulin resistance. These modifications in glucose homeostasis largely stem from alterations in pancreatic function. However, the effects of BPA on the fetal pancreas have never been explored. The present study addressed this important question by examining the effects of prenatal BPA exposure on the mouse fetal pancreatic development. MATERIALS AND METHODS: Pregnant mice were fed a BPA diet (25 mg BPA/kg diet) from embryonic day 7.5 (E7.5) to E18.5. At E18.5, fetal pancreata were collected and analyzed for morphological changes in the endocrine pancreas such as islet size, number and beta and alpha cell distribution. RESULTS: We showed that BPA exposed fetal pancreata had a greater number of islet cell clusters (ICCs; <300 MUm(2); p<0.05) compared with controls. Furthermore, immunohistochemical analysis revealed that prenatal BPA exposure increased both glucagon expression in islets and the numbers of glucagon-expressing islet-cell clusters (p<0.05). CONCLUSION: Considering that ICCs represent the initial stages of islet development in the fetal pancreas, our findings suggest that BPA promotes islet differentiation or delays the conversion of ICCs into mature islets. Moreover, the increase in glucagon expression suggests a potential alteration in the alpha:beta-cell ratio in islets, which may have significant implications for the fetal pancreas both structurally and functionally. This study provides novel insight into the effects of BPA exposure on the fetal pancreata, indicating alterations in glucagon expression in islets and ICCs. PMID- 26812802 TI - Spontaneous conception following GnRHa and progestogen therapy in adenomyosis. AB - Adenomyosis is a common gynaecological disorder that is associated with infertility and miscarriage. We report a case of adenomyosis presented with urinary retention and infertility. The patient successfully conceived spontaneously following GnRHa followed by progestogen therapy. This treatment option might provide a synergistic effect in improving fertility and pregnancy outcome for women with adenomyosis. This modality has no potential surgical risk; it minimises the long-term side effects of GnRHa and also provides luteal support. PMID- 26812803 TI - Physiological and pathological roles of exosomes in the nervous system. AB - Exosomes represent a subtype of extracellular nanovesicles that are generated from the luminal budding of limiting endosomal membranes and subsequent exocytosis. They encapsulate or associate with obsolete molecules to eliminate or to transfer their cargos in intercellular communication. The exosomes are also released and transported between neurons and glia in the nervous system, having a broad impact on nerve development, activation and regeneration. Accumulating evidence suggests that the exosomes are attributed to the pathogenesis of several neurodegenerative diseases such as prion disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, as well as aging, in which the exosomes lack the capacity for cellular self-repair and spread their enclosed pathological agents among neurons. In this article, we review the current proposed functions of exosomes in physiological and pathological processes in the nervous system. PMID- 26812804 TI - Testing Equality in Ordinal Data with Repeated Measurements: A Model-Free Approach. AB - In randomized clinical trials, we often encounter ordinal categorical responses with repeated measurements. We propose a model-free approach with using the generalized odds ratio (GOR) to measure the relative treatment effect. We develop procedures for testing equality of treatment effects and derive interval estimators for the GOR. We further develop a simple procedure for testing the treatment-by-period interaction. To illustrate the use of test procedures and interval estimators developed here, we consider two real-life data sets, one studying the gender effect on pain scores on an ordinal scale after hip joint resurfacing surgeries, and the other investigating the effect of an active hypnotic drug in insomnia patients on ordinal categories of time to falling asleep. PMID- 26812805 TI - Using persistent homology and dynamical distances to analyze protein binding. AB - Persistent homology captures the evolution of topological features of a model as a parameter changes. The most commonly used summary statistics of persistent homology are the barcode and the persistence diagram. Another summary statistic, the persistence landscape, was recently introduced by Bubenik. It is a functional summary, so it is easy to calculate sample means and variances, and it is straightforward to construct various test statistics. Implementing a permutation test we detect conformational changes between closed and open forms of the maltose-binding protein, a large biomolecule consisting of 370 amino acid residues. Furthermore, persistence landscapes can be applied to machine learning methods. A hyperplane from a support vector machine shows the clear separation between the closed and open proteins conformations. Moreover, because our approach captures dynamical properties of the protein our results may help in identifying residues susceptible to ligand binding; we show that the majority of active site residues and allosteric pathway residues are located in the vicinity of the most persistent loop in the corresponding filtered Vietoris-Rips complex. This finding was not observed in the classical anisotropic network model. PMID- 26812806 TI - Assessment of iron in uterine and testicular tissues and hair of free-ranging and household cats. AB - Iron (Fe) represents a highly essential element for various biological processes. In spite of this very little is known as regards its status in mammalian reproductive tissues and factors that may potentially influence it. At the same time, there is an ongoing debate as to whether analyses of the Fe content in hair can provide reliable information on its tissue burden. Therefore, the aim of the present study was to investigate the content of Fe in the testicular and uterine tissues, and hair of the domestic cat (Felis catus) and how this content relates to an animal's age, weight, physical activity, inhabited environment and diet. The median Fe content in the feline reproductive tissues amounted to 50.8 ppm and in hair to 180.2 ppm. As found, free-ranging cats were characterized by a significantly higher Fe content in reproductive tissues, particularly in the uterus. Age, weight and physical activity had no effect on determined Fe levels. The type of commercial diet (wet, dry or combined) given to household cats also had no influence upon Fe status in hair and tissue although males fed exclusively on dry food had a lower Fetestis:Fehair ratio. Hair Fe level was positively correlated with that found in the reproductive tissues (Rs=0.30). This study extends the body of information on Fe distribution in felines, demonstrates the difference between free-ranging and household cats and provides evidence that Fe hair status may, at least partially, reflect the status of this element in the feline reproductive system. PMID- 26812807 TI - Fungal rhinitis in dogs. AB - Fungal rhinitis and sinusitis in dogs are quite common reasons of chronic nasal discharge and rhinoscopy in such cases is commonly suggested. Forty three dogs were examined using rhinoscopy because of the presence of chronic airway symptoms. Clinical examination, routine hematology and serum biochemistry profiles, nasal and frontal sinus radiographs were made in all animals. Additionally, computed tomography in one dog was performed. Samples for histopathology were taken from 9 patients during rhinoscopy, additionally, from 8 of these patients samples for cytopathology were collected by blind nasal swab technique. In 9 of 43 dogs (20,5%), all males aged 1 to 13 years, examinations led to a diagnosis of fungal rhinitis. In 2 cases a diagnosis of fungal rhinitis was obtained based solely on cytopathology, while in 7 cases - mycosis of nasal mucosa was confirmed by histopathology. The present study revealed that cytopathological examination of nasal swabs has a low diagnostic value in the case of nasal infections in dogs. Although, in some dogs cytopathology, together with other widely available diagnostic techniques was sufficient to reliably diagnose fungal rhinitis, histopathology of samples collected during rhinoscopy is still the gold standard in such cases. PMID- 26812808 TI - Hematological parameters in Polish mixed breed rabbits with addition of meat breed blood in the annual cycle. AB - In the paper we studied haematologic values, such as haemoglobin concentration, haematocrit value, thrombocytes, leucocytes: lymphocytes, neutrophils, basophils, eosinophils and monocytes in the pheral blood in Polish mixed-breeds with addition of meat breed blood in order to obtain the reference values which are until now not available for this animals. In studying this indices we took into consideration the impact of the season (spring, summer, autumn, winter), and sex of the animals. The studies have shown a high impact of the season of the year on those rabbits, but only in spring and summer. Moreover we observed that the sex has mean impact on the studied values of haematological parameters in those rabbits. According to our knowledge, this is the first paper on haematologic values in this widely used group of rabbits, so they may serve as reference values. PMID- 26812809 TI - Invasiveness of Listeria monocytogenes strains isolated from animals in Poland. AB - Animals are important reservoir of Listeria monocytogenes, a pathogen causing serious infections in both humans and livestock. However, data on invasiveness of L. monocytogenes strains of animal origin is very scarce. Ability of 18 L. monocytogenes strains of animal origin to invade HT-29 cells was investigated. Plaque forming assay was used to assess invasiveness and ability of the pathogen to spread in the cell line. Almost 40% of L. monocytogenes strains were weakly invasive. It was shown that strains from serogroup 4b exhibited the highest invasiveness, whereas serogroup 1/2b consisted of strains of invasiveness below 0.0001%. Analysis of translated inlA and inlB gene sequences revealed no premature stop codons. Lineage-specific mutations in low invasive strains were identified within inlA and inlB sequences. Our results demonstrate high incidence of low invasive animal L. monocytogenes strains, which may be at least partly explained by unique point mutations in the InlA and InlB. PMID- 26812810 TI - Molecular detection of bovine leukemia virus in peripheral blood of Iranian cattle, camel and sheep. AB - Bovine leukemia virus (BLV) is a deltaretrovirus which infects and induces proliferation of B-lymphocytes in the peripheral blood circulation and in lymphoid organs primarily of cattle, leading to leukemia/lymphoma. This study was carried out to investigate the presence of BLV in cattle, sheep and camels from the Chaharmahal va Bakhtiary and Isfahan provinces in Iran. A total of 874 blood samples collected from cattle, sheep and camels were used in this study to detect BLV using a nested-PCR. The results from this study indicated that 17.2% (n=874) of all blood samples collected were positive for BLV. The percentages of blood samples positive for BLV from cattle, sheep and camels were 22.1 (n=657), 5.3 (n=95) and 0 (n=122) respectively. The results from this study showed that BLV infected cattle and sheep. Camels seemed to be resistant to BLV infection. This study contributes to the nationwide effort to obtain baseline information on the prevalence of BLV, which will assist in planning the control strategy for the disease in Iran. PMID- 26812811 TI - The effect of yeast Yarrowia lipolytica on the antioxidant indices and macro-and microelements in blood plasma of turkey hens. AB - The aim of the study was to assess the effect of different amounts of Yarrowia lipolytica yeast on the redox response and content of macro- and microelements in the blood plasma of turkey hens. The experiment was carried out on 240 turkey hens aged from 1 to 16 weeks. The birds were randomly assigned to 3 experimental groups of 80 birds each. Group I served as a control (K) and did not receive any experimental compounds. The turkey hens from the experimental groups (YL3 and YL6) were administered dried Yarrowia lipolytica yeast in their feed mixtures in the amount of 3% (YL3) or 6% (YL6). Yarrowia lipolytica yeast in the feed mixtures for the turkey hens did not induce oxidation reactions in the organism of the birds. However, an increase in catalase activity and a reduction in the level of LOOH, MDA and vitamin C were observed in the blood plasma of the turkey hens whose diet was supplemented with YL yeast. In the case of other indices, such as superoxide dismutase activity and total antioxidant potential (FRAP), the additive caused no significant changes. Administering Yarrowia lipolytica yeast to turkey hens may stimulate the enzymatic response of the antioxidant system (e.g. increasing catalase activity), mainly by increasing the concentration of iron in the plasma. PMID- 26812812 TI - A multiplex PCR for simultaneous detection of classical swine fever virus, African swine fever virus, highly pathogenic porcine reproductive and respiratory syndrome virus, porcine reproductive and respiratory syndrome virus and pseudorabies in swines. AB - In this assay, we developed and evaluated a multiplex PCR (mPCR) for its ability in detecting multiple infections of swine simultaneously. Four pairs of primers were used to detect five viruses. Specific primers were designed for classical swine fever virus (CSFV), African swine fever virus (ASFV) and pseudorabies (PRV). A pair of primers was designed prudently for two different types of porcine reproductive and respiratory syndrome virus that respectively were porcine reproductive and respiratory syndrome virus (PRRSV), highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV). The detection limits of the mPCR were 1.09 * 104, 1.50 * 103, 2.10 * 103, 1.30 * 103 and 8.97 * 102 copies/reaction for CSFV, ASFV, HP-PRRSV, PRRSV and PRV, respectively. A total of 49 clinical specimens were tested by the mPCR, and the result showed that co-infection by two or three viruses was 51%. In conclusion, the PCR is a useful tool for clinical diagnosis of not only single infections but also mixed infections in swines. PMID- 26812813 TI - Selection and electrophoretic characterization of Salmonella enterica subsp. enterica biocide variants resistant to antibiotics. AB - The proposed research outlines a serious common concern of Salmonella resistance to antimicrobials following prolonged exposure to the disinfectants (biocides). These phenotypes of bacteria could potentially result in hard to treat infections. Typical for avian sources, biocide sensitive S. enterica subsp. enterica serovars: Typhimurium, Enteritidis, Virchow and Zanzibar and their isogenic biocide-tolerant variants were studied in order to investigate bacteriostatic effect of two commercially available biocide formulations: potassium peroxymonosulfate (P) and dodecylamine based structure (triamine, D). We found that cultivating of the bacteria in the medium supplemented with a blend containing P did not influence their antibiotic susceptibility pattern. In contrast, tolerance of bacteria to D compound resulted in resistance to co trimoxazole, cefotaxime and ciprofloxacin of which two cefotaxime and ciprofloxacin are used commonly for the treatment of invasive Salmonella infections in humans. The dependency between OMP patterns and the level of Salmonella survival in media containing the biocides was observed merely in serovar Typhimurium. In conclusion, these results suggest that Salmonella strains challenged by prolonged treatment with the disinfectants become resistant to antibiotics, however it depends on Salmonella serovar and the chemical used. This paper also highlights the loop-mediated isothermal amplification (LAMP) as a technique that offers great benefits to microbiological detecting of Salmonella species in the samples. PMID- 26812814 TI - Effects of storage in different semen extenders on the pre-freezing and post thawing quality of boar spermatozoa. AB - The aim of this study was to investigate the effects of storage of semen in different commercial extenders on the pre-freezing and post-thawing quality of boar spermatozoa. Semen was diluted in BTS, Androhep (AH) and Gedil (GD), stored for 24 h at 17 degrees C, and then frozen in accordance with the cryopreservation protocol. Analyses of the quality of spermatozoa included: motility, normal apical ridge (NAR) acrosome, plasma membrane integrity (PMI), mitochondrial membrane potential (MMP), measurements of ATP content and activity of superoxidase dismutase (SOD) and glutathione peroxidase (GPx). Prior to the freezing process, no significant effect of the extender on the sperm quality parameters was noted. After thawing the spermatozoa it was demonstrated that the type of extender used influenced PMI, MMP, ATP content and activity of GPx. In the AH extender the percentage of spermatozoa with PMI and ATP content in spermatozoa was significantly higher (P<0.05) as compared to the BTS or GD extenders. In addition, semen stored in the AH was characterised by a statistically higher (P<0.05) percentage of spermatozoa with MMP and increased activity of GPx as compared with the BTS. The results obtained indicate that for the cryopreservation process, boar spermatozoa stored for 24 hours in liquid state can be used. However, the type of extender used prior to freezing may have a significant effect on the post-thawing quality of the spermatozoa. The AH extender better secured the quality of thawed boar spermatozoa as compared with the BTS or GD. PMID- 26812815 TI - Effects of dietary supplementation with sage (Salvia officinalis L.) essential oil on antioxidant status and duodenal wall integrity of laying strain growers. AB - The objective of this study was to compare the influence of four different concentrations of Salvia officinalis essential oil (EO) on animal health. A total of 50 laying strain chicks were randomly divided at the day of hatching into five dietary-treatment groups. Control group was given the basal diet (BD), the other four experimental groups contained BD supplemented with 0.1, 0.25, 0.5, 1.0 g S. officinalis EO/kg diet, respectively. 0.1 g/kg EO increased glutathion peroxidase activity (GPx) in duodenal mucosa, liver and kidney, phagocytic activity in blood (PA), transepithelial electrical resistance (TEER) in duodenal tissue and decreased malondialdehyde (MDA) concentration in plasma and liver. 0.25 g/kg EO increased GPx in liver, total antioxidant status (TAS) in plasma, PA in blood and TEER in duodenal tissue. Our results demonstrate that lower concentrations of EO improve animals' health status, and that it is necessary keep in mind the selection of sufficient concentration of EO used as animal feed additive. PMID- 26812816 TI - In vitro study of the effect of corn dried distillers grains with solubles on rumen fermentation in sheep. AB - The aim of the in vitro study was to determine the effect of corn dried distillers grains with solubles (corn DDGS), used as a replacement for the concentrate ingredients of sheep diet, on rumen fermentation. The material for the study was the ruminal fluid of Polish Merino sheep which was incubated during 4-, 8- or 24-hour periods. Five groups of samples were prepared for in vitro fermentation: C - control, incubated with the substrate consisting of the concentrate ingredients; D1, D2 and D3, where DDGS was used as a substrate added in proportions of 10, 20 and 30% of dry matter of the concentrate; and D4, where 100% DDGS was used as a substrate. After fermentation, the gas and short chain fatty acids (SCFAs) analyses were performed using gas chromatography. The ammonia concentration and pH were also determined, and the SCFA utilization index (NGR), the fermentation efficiency (FE) and the index of cell yield of ruminal microorganisms (CY) were calculated. This research showed no effect of DDGS on the methane emission. The positive correlations between the amount of methane and ammonia concentrations in the 8- and 24-hour fermentation periods were found. DDGS addition increased propionate proportion, but decreased production of acetate (p<0.01). Additionally, D1, D2, D3 and D4 substrates lowered isobutyrate (p<0.05) and isovalerate (p<0.01) production. Based on the results obtained, it can be stated that partial substitution of the concentrate ingredients with DDGS did not have deleterious effect on sheep rumen fermentation processes. PMID- 26812818 TI - Immunohistochemical evaluation of hippocampal CA1 region astrocytes in 10-day-old rats after monosodium glutamate treatment. AB - High concentration of glutamate (Glu) is excitotoxic for nervous system structures. This may lead to glial reactivity ie. increased expression of glial fibrillary acidic protein (GFAP) and S100beta protein, and also to hypertrophy and proliferation of cells which are determined by the presence of Ki-67 antigen. The aim of the study was to analyse the immunoreactivity of the GFAP, S100beta and Ki-67 proteins in astrocytes of hippocampal CA1 region in young rats after administration of monosodium glutamate (MSG) at two doses: 2 g/kg b.w. (I group) and 4 g/kg b.w. (II group). In rats from I and II group morphologically altered astrocytes with the GFAP expression were observed in the SLM of the hippocampal CA1 region. The cells had eccentrically located nuclei and on the opposite site of the nuclei there were single or double, long and weakly branched processes. Moreover, in the SLM the increase of the number of GFAP and S100beta immunopositive astrocytes and nuclei with Ki-67 expression, in contrary to control individuals, was observed. These results suggest the increased expression of the proteins in early reactions or hyperplasia which, together with cell hypertrophy, indicate late reactivity of astroglia in response to glutamate noxious effect. PMID- 26812817 TI - Is downer cow syndrome related to chronic botulism? AB - The present work was directed to investigate the relationship between Downer cow syndrome (DCS) and chronic botulism in dairy cattle. For this purpose, a total of 52 fresh calving downer cows and 206 apparently healthy cows at 14 dairy farms were investigated for Clostridium botulinum ABE and CD antibody levels, C. botulinum and botulinum neurotoxin in rumen fluids as well as in faeces. Results indicated that the downer cows had higher IgG titers for C. botulinum ABE and CD than the healthy cows. All tested rumen fluids were negative for BoNT and C. botulinum. BoNT/D, however, and C. botulinum type D spores were detected in faecal samples of healthy and downer cows in the selected farms. In conclusion, the presence of a significantly higher C. botulinum ABE and CD antibody levels in DCS cows than in the healthy animals suggests that chronic C. botulinum toxico infection could be a predisposing factor for DCS. PMID- 26812819 TI - Detection of Pentatrichomonas hominis in dogs using real-time PCR. AB - Trichomonadidae family is a protozoan occurring in different animal species. It inhabits the gastrointestinal and urinary tracts. P. hominis is rarely found in faecal samples of dogs, and its identification and differentiation from other trichomonads by light microscopy are difficult. Methods of molecular biology are the most effective in this case, because they confirm the presence of the specific species in animal organisms, irrespective of the protozoan form. The aim of this study was to find P. hominis in selected dog kennels in North-Eastern Poland. Forty-one faecal samples of dogs from 7 dog kennels were examined. The occurrence of P. hominis in 5 faecal samples of dogs with no symptoms of diarrhoea was the first one to be confirmed in Poland. PMID- 26812820 TI - Etiology and pathology of epidemic outbreaks of avian influenza H5N1 infection in Egyptian chicken farms. AB - Epidemic outbreaks of avian influenza (AI) virus H5N1 have been frequently reported in Egypt during the last nine years. Here we investigate the involvement of AI H5N1 in outbreaks of acute respiratory disease that occurred in several commercial chicken farms in Egypt in 2011, and we describe to the pathology caused by the virus in the course of the outbreak. Twenty-one chicken farms with history of acute respiratory symptoms and high mortalities were screened for AI H5N1. Virus identification was based on hemagglutination inhibition test, and PCR detection and sequencing of the hemagglutinin and neuraminidase genes. Virus distribution was determined by immunohistochemical staining of AI antigens in organs of infected birds. Standard H&E staining was performed for histological examination of affected organs. Eighty-one % of the examined birds, representing 100% of the screened farms, were positive for AI H5N1 virus. Phylogenetic analysis of the hemagglutinin and neuraminidase genes of the isolated virus reveals its affiliation to clade 2.2.1. Viral antigens were localized in the endothelial cells of the heart, liver, lungs and skin, where pathological lesions including congestion, hemorrhages, multifocal inflammation and necrosis were concurrently observed. According to the pattern of the viral antigen and lesion distribution in the visceral organs, we suggest cardiovascular and circulatory failures as the probable cause of death during these outbreaks. In conclusion, the present study further confirms the epidemic status of AI H5N1 virus in Egypt and reveals the highly pathogenic nature of the local isolates. PMID- 26812821 TI - Biofilm-formation by Staphylococcus aureus and Staphylococcus epidermidis isolates from subclinical mastitis in conditions mimicking the udder environment. AB - Staphylococcus is the genus most commonly isolated from bovine mastitis in many countries. It may express several virulence factors including biofilm formation, which may protect the bacterial community from antimicrobials' action, preventing these compounds from reaching its interior, where they reach subinhibitory concentrations (subMIC). Most biofilm production assays are performed in static conditions, while studies regarding antimicrobial resistance usually do not resemble the udder environment because they are performed at high concentrations. In this study we evaluated the influence of dynamic conditions and media, including Mueller Hinton Broth (MHB) and UHT whole milk (WM), as well as the effect of subMIC concentrations of five different antimicrobial agents on biofilm formation by staphylococci isolated from subclinical mastitis. Results suggest that dynamic conditions and media may influence biofilm formation and revealed that milking simulation may significantly increase biofilm production. Sub-MIC concentrations decrease biofilm formation in MHB but increase in WM, suggesting a protective role of milk against antimicrobial compounds' action. Therefore, in vitro conditions that simulate the udder environment and in vivo conditions should be included as one of the parameters in evaluation of biofilm producing strains, in order to provide more reliable results. PMID- 26812822 TI - Can liquorice extract and herbal solution prevent colonic mucosa damage caused by robenacoxib in dogs? AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in animals, especially in dogs, to manage pain due to inflammatory disease. This study investigated whether plant drugs can prevent mucosal injury induced by robenacoxib. We used fifteen healthy beagle dogs (7 male and 8 female) aged 4 months, weighing 4.2-5.1 kg at the beginning of the study. Endoscopy and biopsy of the colon were performed before and on the 21 day treatment with robenacoxib (1), robenacoxib, herbal solution with liquorice extract (2), placebo - an empty capsule (3). There were 5 animals in each group. The greatest microscopic damage in the colon was observed in animals which received robenacoxib. Plant drug administration reduced the severity of lesions in the colon when administered with robenacoxib (ARI = - 0.15). CONCLUSION: concurrent administration of liquorice extract and plant solution with robenacoxib was associated with significant decreased severity of the robenacoxib-induced colonic mucosal lesions. PMID- 26812823 TI - Evaluation of the udder health status in subclinical mastitis affected dairy cows through bacteriological culture, somatic cell count and thermographic imaging. AB - Subclinical mastitis in dairy cows is a big economic loss for farmers. The monitoring of subclinical mastitis is usually performed through Somatic Cell Count (SCC) in farm but there is the need of new diagnostic systems able to quickly identify cows affected by subclinical infections of the udder. The aim of this study was to evaluate the potential application of thermographic imaging compared to SCC and bacteriological culture for infection detection in cow affected by subclinical mastitis and possibly to discriminate between different pathogens. In this study we evaluated the udder health status of 98 Holstein Friesian dairy cows with high SCC in 4 farms. From each cow a sample of milk was collected from all the functional quarters and submitted to bacteriological culture, SCC and Mycoplasma spp. culture. A thermographic image was taken from each functional udder quarter and nipple. Pearson's correlations and Analysis of Variance were performed in order to evaluate the different diagnostic techniques. The most frequent pathogen isolated was Staphylococcus aureus followed by Coagulase Negative Staphylococci (CNS), Streptococcus uberis, Streptococcus agalactiae and others. The Somatic Cell Score (SCS) was able to discriminate (p<0.05) cows positive for a pathogen from cows negative at the bacteriological culture except for cows with infection caused by CNS. Infrared thermography was correlated to SCS (p<0.05) but was not able to discriminate between positive and negative cows. Thermographic imaging seems to be promising in evaluating the inflammation status of cows affected by subclinical mastitis but seems to have a poor diagnostic value. PMID- 26812825 TI - Influence of chamber type integrated with computer-assisted semen analysis (CASA) system on the results of boar semen evaluation. AB - The objective of the study was to evaluate the effect of different types of chambers used in computer-assisted semen analysis (CASA) on boar sperm concentration and motility parameters. CASA measurements were performed on 45 ejaculates by comparing three commonly used chambers: Leja chamber (LJ), Makler chamber (MK) and microscopic slide-coverslip (SL). Concentration results obtained with CASA were verified by manual counting on a Burker hemocytometer (BH). No significant differences were found between the concentrations determined with BH vs. LJ and SL, whereas higher (p<0.01) values of this parameter were obtained with MK. Compared to MK and SL, significantly higher values were recorded in LJ for velocity (VCL and VAP) as well as amplitude of the lateral head displacement (ALH) and beat cross frequency (BCF), which was associated with significantly higher percentages of motile, progressively motile and rapidly progressive motile spermatozoa. Higher values for the linearity (LIN) and straightness (STR) of sperm movement were obtained for the analysis performed in MK and SL. In both these chambers, the results of all the linearity and kinetic parameters of sperm were similar (p>0.05). The results obtained show that CASA assessment of boar semen should account for the effect of counting chamber on the results of sperm motility and concentration, which confirms the need for further study on standardizing the automatic analysis of boar semen. PMID- 26812824 TI - Biochemical and immunological responses of young turkeys to vaccination against Ornithobacterium rhinotraheale and different levels of dietary methionine. AB - The objective of this study was to verify the hypothesis that increasing levels of dietary methionine can stimulate the mechanisms of cell-mediated and humoral immunity in young turkeys. The blood and organs involved in cell-mediated and humoral immune responses were analyzed in 8-week-old turkeys that had been vaccinated against Ornithobacterium rhinotraheale (ORT) infection (on days 17 and 48). The birds were fed diets with a low (LM), medium (MM) and high (HM) methionine content (0.45 and 0.40%, 0.60 and 0.51%, 0.71 and 0.57% in weeks 1 - 4 and 5 - 8, respectively). Dietary methionine supplementation led to a significant increase in body weights of turkeys at 56 days of age, from 3532 g in group LM to 3720 g in group MM and 3760 g in group HM (p=0.001). A significant increase in vaccine-induced antibody titers against ORT was noted in group HM relative to group LM (p=0.006). Increasing levels of methionine had no significant effect on total serum IgG nor IgM levels and most serum biochemical parameters, TP, ALB, GLOB, GLU, AST, ALP, P and Ca. In comparison with group LM, group HM turkeys were characterized by a lower percentage of IgM+ B cell subpopulation in the blood and bursa of Fabricius. The percentages of CD4+ and CD8+ T cell subpopulations in the bursa of Fabricius in group HM were significantly different from those found in groups LM and MM. The highest percentages of CD4+ T cells and CD8+ T cells in the spleen were observed in groups LM (p<0.001) and HM (p=0.04), respectively. The differences were statistically significant relative to the remaining groups. Turkeys of group LM were characterized by a lower CD4+ T cell percentage in the thymus (p<0.001) and a lower CD8+ T cell percentage in the cecal tonsils (CTs) (p<0.01). Vaccination against ORT resulted in a significant increase in the percentage of CD4+CD8+ T cell subpopulation and a decrease in the percentage of CD8+ T cell subset in the spleen. PMID- 26812826 TI - Prevalence and risk factors for Lawsonia intracellularis, Brachyspira hyodysenteriae and Salmonella spp. in finishing pigs in Polish farrow-to-finish swine herds. AB - The aim of the study was to estimate the herd-level, within-herd prevalence, the frequency of mixed infections and risk factors for L. intracellularis, B. hyodysenteriae and Salmonella spp. in selected farrow-to-finish Polish pig herds. A total of 254 pooled fecal samples were collected from 9 to 24 week-old pigs in 70 herds. Real time PCR for detection of L. intracellularis and B. hyodysenteriae was performed. For Salmonella spp. bacteriological examination was performed. The herd-level prevalences of L. intracellularis, B. hyodysenteriae and Salmonella spp. among examined herds were 65.7%, 1.4% and 8.6%, respectively. The within herd prevalences (in positive herds) for L. intracellularis, B. hyodysenteriae and Salmonella spp. were 51.5%, 75.0% and 30.4%, respectively. All herds with diarrhea observed during sampling were infected with L. intracellularis and 60% of herds with no diarrhea at the moment of sampling were infected with L. intracellularis (p=0.035). In herds with more than 200 sows the prevalence of Salmonella spp. was significantly higher compared to herds with less than 200 sows (p=0.027). In herds where all-in/all-out (AIAO) was respected, prevalence of L. intracellularis was significantly lower than in herds where this rule was not kept (p=0.024). Obtained results confirm that L. intracellularis is the major cause of bacterial diarrhea in finishing pigs. The present study identified AIAO and herd size as a risk factor, at the herd level, for L. intracellularis and Salmonella spp., respectively. PMID- 26812827 TI - Application of real-time PCR for evaluation of distribution of equine herpesvirus type 1 in tissues of aborted fetuses. AB - A highly sensitive and specific real-time PCR assay was used for detection and quantitation of equine herpesvirus type 1 (EHV-1) in the different internal organs of aborted fetuses. Tissue samples from 23 aborted fetuses submitted to the Department of Virology of the National Veterinary Research Institute in Pulawy between 2012 and 2013 were used for testing. Total DNA was extracted using a phenol-chloroform-isoamyl alcohol standard protocol. A real-time PCR with forward and reverse primers encompassing a highly conserved region encoding viral glycoprotein B was adapted for diagnosis of EHV-1 infection. The detection limit of the assay was shown to be 6.0 * 100 of viral DNA copies and the obtained standard curve exhibited a linear range from 100 to 107 molecules. Sixteen out of twenty three aborted fetuses (69.5%) were positive for EHV-1 in real-time PCR. The highest EHV-1 DNA load was obtained for liver (mean Ct value: 15.7) and lung (18.2) samples, while the lowest was in the thymus (29.6) and placenta (28.4). PMID- 26812828 TI - Retrospective analysis of co-occurrence of congenital aortic stenosis and pulmonary artery stenosis in dogs. AB - The study has focused on the retrospective analysis of cases of coexisting congenital aortic stenosis (AS) and pulmonary artery stenosis (PS) in dogs. The research included 5463 dogs which were referred for cardiological examination (including clinical examination, ECG and echocardiography) between 2004 and 2014. Aortic stenosis and PS stenosis were detected in 31 dogs. This complex defect was the most commonly diagnosed in Boxers - 7 dogs, other breeds were represented by: 4 cross-breed dogs, 2 Bichon Maltais, 3 Miniature Pinschers, 2 Bernese Mountain Dogs, 2 French Bulldogs, and individuals of following breeds: Bichon Frise, Bull Terrier, Czech Wolfdog, German Shepherd, Hairless Chinese Crested Dog, Miniature Schnauzer, Pug, Rottweiler, Samoyed, West Highland White Terrier and Yorkshire Terrier. In all the dogs, the murmurs could be heard, graded from 2 to 5 (on a scale of 1-6). Besides, in 9 cases other congenital defects were diagnosed: patent ductus arteriosus, mitral valve dysplasia, pulmonary or aortic valve regurgitation, tricuspid valve dysplasia, ventricular or atrial septal defect. The majority of the dogs suffered from pulmonary valvular stenosis (1 dog had supravalvular pulmonary artery stenosis) and subvalvular aortic stenosis (2 dogs had valvular aortic stenosis). Conclusions and clinical relevance - co-occurrence of AS and PS is the most common complex congenital heart defect. Boxer breed was predisposed to this complex defect. It was found that coexisting AS and PS is more common in male dogs and the degree of PS and AS was mostly similar. PMID- 26812829 TI - Spleen content of selected polyphenols, splenocytes morphology and function in mice fed Rhodiola kirilowii extracts during pregnancy and lactation. AB - The genus Rhodiola (Crassulaceae) consists of many species, growing mainly in Asia and traditionally used as adaptogens and anti-inflammatory drugs. In order to elaborate herbal immunostimulator which could be safely given to pregnant women, we performed a study on immunotropic effects of feeding pregnant and lactating mice Rhodiola kirilowii extracts. This paper presents the results of the first part of our study - spleen content of selected polyphenols, spleen cellularity, splenocytes phenotype and their response to mitogens. Experiments were performed on adult inbred females of Balb/c strain, mated with adult males. Females, since copulatory plug was noted, up to the 28-th day after delivery were fed daily with 20 mg/kg b.m. water (RKW) or hydro-alcoholic (RKW-A) extracts of Rhodiola kirilowii. RESULTS: 1. Significantly lower proportion of pregnant mice in experimental groups than in the control. 2. Cellularity of spleen and flavonol quercetin spleen concentration were significantly lower in experimental groups in comparison to the controls. 3. Flavanols ((+)-catechin and epicatechin) levels were significantly higher in the spleens of experimental mice than in the controls. 4. Positive correlation between spleen cellularity and quercetin, and negative correlation between spleen cellularity and epicatechin content were observed. 5. Spleen mass and spleen lymphocytes phenotype and proliferation in RKW and RKW-A fed mice did not differ from the control. These results, together with suspicion of some embryo-toxicity, are worrying and eliminate the possibility of use Rhodiola kirilowii extracts for long-term treatment in pregnant females. PMID- 26812830 TI - Immunocytochemical detection of calretinin in the claustrum and endopiriform nucleus of the chinchilla. AB - Calretinin (CR) as a buffer and sensor protein plays an important role in regulatory processes of Ca2+ and anty-apoptotic cellular protection. In the present study, immunohistochemical peroxidase-antiperoxidase (PAP) method was used in order to determine the numbers, morphology, morphometry and distribution pattern of CR in neurons of the chinchilla's claustrum (Cl) and endopiriform nucleus (EN). In Cl and EN the presence of several classes of neurons with different immunoreactivity to CR was found. In Cl, CR-immunoreactive (IR) neurons were predominantly found in close vicinity to insular border while CR-IR neurons were evenly scattered throughout EN. In general, immunoreaction to CR was observed in neuronal cytoplasm, nucleus and in fibres-like nerve extensions. Statistical analysis showed the differences between average large diameter as well as cross-sectional area of CR-IR neurons present in Cl and EN. It is suggested, that CR acting as a calcium binding protein may play a role in neuronal network. Further co-localization studies are necessary to fully elucidate neurophysiology and neuropathology of the chinchilla's Cl and EN neurons. PMID- 26812831 TI - Evaluation of selected serum biochemical and haematological parameters in gilts exposed per os to 100 ppb of zearalenone. AB - Zearalenone (ZEN) widely contaminates animal feed of plant origin. The recommended safe concentrations of ZEN in feeds for various animal species are set mainly based on the mycotoxin's hormonal properties (NOEL). Our growing knowledge about biologically active concentrations of ZEN, molecular mechanisms and cells/tissues targeted by ZEN indicates that the harmful effects exerted by this mycotoxin on animals may be far greater than previously believed. This experiment was performed on pre-pubertal gilts divided into a control group (n=9) and an experimental group (ZEN, n=9). The control group received placebo, whereas the experimental group was administered ZEN at a dose of 0.1 mg/kg feed (equivalent to 5 MUg/kg BW/day) for 42 days. On days 14, 28 and 42 blood samples were collected from the animals to determine the concentrations of selected zearalenols, serum biochemical and haematological parameters. Conjugated ZEN was found in the blood serum of the experimental gilts. Changes in the analysed biochemical parameters included a transient increase in albumin and cholesterol levels. A statistically significant increase in the concentrations of neutrophilic and acidophilic granulocytes was observed in the white blood cell system. The results indicate that long-term per os exposure of pre-pubertal gilts to low doses of ZEN (below NOEL) has a modulatory effect on liver function and white blood cells. PMID- 26812832 TI - Suitability of using serum hialuronic acid concentrations in the diagnosis of canine liver fibrosis. AB - There are multiple dynamic changes associated with the metabolism of the extracellular matrix (ECM) which occur in the course of liver fibrosis. Therefore, the evaluation of parameters reflecting the deposition of ECM, the activity of myofibroblasts and the synthesis and degradation of collagen may aid in the diagnosis of liver fibrosis. Hyaluronic acid is considered to be a marker of ECM deposition. It is a glycosaminoglycan synthesized by hepatic stellate cells and degraded by hepatic sinusoidal endothelial cells. The aim of this study was to evaluate the concentration of hyaluronic acid in dogs with different degrees of liver fibrosis. The study was carried out on 29 dogs with liver disease. A core needle biopsy of the liver was performed in order to assess the degree of hepatic inflammation. Then, hyaluronic acid serum concentrations were measured. The dogs were divided into five groups based on the histopathological examination and the evaluation of the degree of hepatic fibrosis. The study showed that serum hyaluronic acid concentrations were low in patients with first stage liver fibrosis and in controls, while they were twice as high as control values in the group of dogs with second stage liver fibrosis. These concentrations were three-fold greater than control values in patients with third stage liver fibrosis, and seven-fold greater in patients with liver cirrhosis. Based on the results, it was concluded that serum hyaluronic acid is a useful marker of liver fibrosis and may aid in determining the degree of its advancement. PMID- 26812834 TI - A serological and molecular study on the occurrence of mycoplasmas in European bison (Bison bonasus) from two areas of Eastern Poland. AB - European bison (Bison bonasus) from two different areas of Eastern Poland showing gross pathology possibly associated with mycoplasma infections were tested for ruminant Mycoplasma species using serological and molecular methods. Fifty-five samples, blood or tissue were collected from 28 animals during 2013-2014. Six sera were positive for Mycoplasma bovis. The ELISA and complement fixation test for Mycoplasma mycoides subsp. mycoides gave a few weak reactions, but were negative by immunoblotting and molecular methods. PMID- 26812833 TI - Expression of goose parvovirus whole VP3 protein and its epitopes in Escherichia coli cells. AB - The aim of this study was the expression of goose parvovirus capsid protein (VP3) and its epitopes in Escherichia coli cells. Expression of the whole VP3 protein provided an insufficient amount of protein. In contrast, the expression of two VP3 epitopes (VP3ep4, VP3ep6) in E. coli, resulted in very high expression levels. This may suggest that smaller parts of the GPV antigenic determinants are more efficiently expressed than the complete VP3 gene. PMID- 26812835 TI - Winter blood values of selected parameters in a group of non-hibernating captive brown bears (Ursus arctos). AB - Bears undergo some significant changes reflected in blood values during winter season. The most significant are reduced urea and increased creatinine, by some authors considered to be physiological indicators of hibernation. Studied group of six captive brown bears (Ursus arctos) showed decreased activity in winter but were accepting food and walked outdoors. Blood parameters assessed in February 2011 revealed mean values of leucocytes and neutrophils as significantly lower, and creatinine significantly increased compared to captive and free living bears sampled during other seasons when bears are active. PMID- 26812836 TI - Interethnic variability of pharmacogenetic biomarkers in Mexican healthy volunteers: a report from the RIBEF (Ibero-American Network of Pharmacogenetics and Pharmacogenomics). AB - Mexico presents a complex population diversity integrated by Mexican indigenous (MI) (7% of Mexico's population) and Mexican mestizos (MMs). This composition highlights the importance of pharmacogenetic studies in Mexican populations. The aims of this study were to analyze the reported frequencies of the most relevant pharmacogenetic biomarkers and metabolic phenotypes in healthy volunteers from Mexican populations and to assess its interethnic variability across MI and MM populations. After a literature search in PubMed, and according to previously defined inclusion criteria, 63 pharmacogenetic studies performed in Mexican healthy volunteers up to date were selected. These reports comprised 56,292 healthy volunteers (71.58% MM). Allele frequencies in 31 pharmacogenetic biomarkers, from 121 searched, are described. Nine of these biomarkers presented variation within MM and MI groups. The frequencies of CYP2D6*3, *4, *5, *10, *17, *35 and *41 alleles in the MM group were different from those reported in the MI group. CYP2C9*2 and *3 alleles were more frequent in MM than in MI populations (chi2 test, p<0.05). CYP2C19*3 allele was not found in the MM or MI populations reported. For UGT1A1*28, only one study was found. HLA-A*31:01 and HLA-B*15:02 were present in some MM and MI populations. Poor metabolizers for CYP2D6 and CYP2C9 were more frequent in MM than in MI groups (chi2 test, p<0.05). Only 26% of the relevant pharmacogenetic biomarkers searched have been studied in Mexican healthy volunteers; therefore, further studies are warranted. The frequency variation of biomarkers in MM and MI populations could be important for the clinical implementation of pharmacogenetics in Mexico. PMID- 26812837 TI - Elective Laparoscopic Cholecystectomy--Is It Safe In The Hands Of Residents During Training? AB - The aim of the study was to assess safety of elective laparoscopic cholecystectomy (LC) performed by residents that are undergoing training in general surgery. MATERIAL AND METHODS: A retrospective analysis was conducted on 330 patients operated electively due to cholelithiasis. Patients with acute cholecystitis, choledocholithiasis, undergoing cholecystectomy as a part of more extensive operation and patients with gall-bladder cancer were excluded. Group 1 included patients operated by resident, group 2--by specialist. Duration of operation, mean blood loss, number of major complications, number of conversions to the open technique and conversions of the operator, reoperations and length of hospital stay were analyzed. RESULTS: Mean operative time overall was 81 min (25 170, SD +/- 28.6) and 71 min (30-210, SD +/- 29.1) in groups 1 and 2 respectively (p=0.00009). Mean blood loss in group 1 was 45 +/- 68.2 ml and in group 2 - 41 +/- 73.4 ml (p=0.23). Six major complications has occurred (1.81%) - 2 (2%) in group 1 and 4 (1.7%) in group 2. 18 cases (15.5%) of conversion of the operator occurred in group 1, and 6 cases (2.6%) of conversion of the operator happened in group 2. Average LOS was 1.9 days in group 1 and 2.3 days in group 2 (p=0.03979). CONCLUSIONS: Elective LC performed by a supervised resident is a safe procedure. Tactics of "conversion of operator" allowed to prevent major complications. Longer LC by residents is natural during the learning curve. Modifications of residency program in the field of laparoscopy may increase its accessibility. PMID- 26812838 TI - Satisfaction With Life And Disease Acceptance By Patients With A Stomy Related To Surgical Treatment Of The Rectal Cancer--Determinants Of Quality Of Life? AB - Satisfaction with life and disease acceptance by patients with a stomy related to surgical treatment of the rectal cancer depend on multiple factors. Such factors as social support, life conditions and time that elapsed after stomy creation, are very important in this context. The aim of the study was to conduct an early evaluation of life satisfaction and disease acceptance by patients with a stomy related to surgical treatment of the rectal cancer. MATERIAL AND METHODS: The study was conducted at Dr. Jan Biziel University Hospital No. 2 in Bydgoszcz and at the prof. F. Lukaszczyk Oncology Centre in Bydgoszcz in 2014. The final analysis included 96 subjects aged 41-87 years (median 59 years). Satisfaction With Life Scale (SWLS) and Acceptance of Illness Scale (AIS) adapted by Zygfryd Juczynski, were used in this study. RESULTS: Most patients had satisfaction with life score of 5 or 6, 23 (24%) and 28 (29.2%) subjects, respectively. Twenty nine (30.2%) study subjects had low satisfaction level, while 16 (16.7%) had high satisfaction level. Average disease acceptance score was 23.2 points. Most patients, 71 (74%) had a moderate disease acceptance score, while the lowest number of subjects, 9 (9.4%), had high disease acceptance score. None of the study subjects who were under the care of a psychologist (14/100%) did not have a low acceptance level. CONCLUSIONS: Half of the study subjects had a moderate level of satisfaction with life. Most patients with stomy related to surgical treatment of the rectal cancer in an early postoperative period had moderate level of the disease acceptance. Patients with high level of satisfaction with life, accept the disease better. Few patients who used help by a psychologist, were two- and three-fold more likely to have higher level of satisfaction with life and disease acceptance, respectively. PMID- 26812839 TI - Effects Of Gelatine-Coated Vascular Grafts On Human Neutrophils. AB - The aim of the study was to investigate the immune-modulatory potential of commercially available PTFE and polyester vascular grafts with and without gelatine-coating. The biomaterial-cell-interaction was characterized by changes of established parameters such as PMN-related receptors/mediators, phagocytosis potential and capacity as well as the effect of an additional plasma-dependent modulation. MATERIAL AND METHODS: By means of a standardized experimental in vitro model, various vascular graft material (PTFE/polyester/uncoated/gelatine coated) was used for incubation with or without plasma and co-culturing with human neutrophile granulocytes (PMN) followed by analysis of representative receptors and mediators (CD62L, CD11b, CXCR2, fMLP-R, IL-8, Elastase, LTB4). Oxidative burst assessed phagocytosis capacity. RESULTS: Comparing the vascular grafts, un-coated PTFE induced the lowest magnitude of cell stimulation whereas in case of gelatine-coating, cell response exceeded those of the other vascular grafts. This was also found comparing the polyester-based prosthetic material. Gelatine-coated polyester led to a more pronounced release of elastase than gelatine-coated PTFE and the uncoated materials. The results of oxidative burst indicated a reduced phagocytosis capacity in case of gelatine-coated polyester. Plasma incubation did also provide an impact on the cellular response. While in case of gelatine-coating, PMN-related receptor stimulation became lower, it increased by native polyester. The latter one did also induce more mediators such as IL-8 and LTB4 than gelatine-coated material. CONCLUSIONS: There have been no extensive data on cell-cell interactions, cytokines and general histo /hemocompatibility of human cells by the new generation of vascular grafts. It remains still open whether healing process and infectious resistance can be compromised by material-dependent over-stimulation or reduced phagocytosis potential of the immune cells of the primary unspecific immune response induced by gelatine-coated materials. PMID- 26812840 TI - Comfort During Digital Rectal Examination - Patient Preference. AB - The sex and age of the physician performing the digital rectal examination (DRE) procedure is one of the parameters influencing patients' comfort. It is postulated that the stress related to DRE during admission to the surgical ward may affect the compliance. The aim of the study was to characterize patients' preferences according to their sex, age, socioeconomic status and according to DRE-related variables. MATERIAL AND METHODS: Patients admitted to the Department of General and Colorectal Surgery at Medical University in Lodz between October 2014 and June 2015 were asked to complete a questionnaire regarding their sex, age, ethnic background, socioeconomic status and preference for a physician performing the DRE during admission to the surgical ward. RESULTS: The study enrolled 225 patients, 52% (n=117) women and 48% (n=108) men. Most patients 73.3% (n=244) expressed no preference for sex of the physician performing the DRE during admission, while 22.7% (n=51) preferred a same-sex physician. Analysis showed that the age, female sex, lower education status, small amount of comorbidities and number of hospitalizations, and no previous colonoscopy experience were all associated with preference for a same-sex physician. CONCLUSIONS: In our study most patients expressed no preference for sex of the physician performing the DRE during admission to the surgical ward. However, over one-tenth of patients reported such preferences. Most of these patients preferred a same-sex physician. It is important to offer these patients the choice of physician performing the DRE. Addressing patients' preferences may improve the atmosphere in the clinical environment, reduce stress, and facilitate better treatment. PMID- 26812841 TI - Patients' Awareness Of The Prevention And Treatment Of Colorectal Cancer. AB - The aim of the study was to assess patients' awareness of the prevention and treatment of colorectal cancer. MATERIAL AND METHODS: Patients diagnosed with colorectal cancer, hospitalised at the Department of General and Colorectal Surgery of the Medical University in Lodz during the period from January 2015 to April 2015, were asked to complete a questionnaire concerning their families' medical case record, factors predisposing them to the development of colorectal cancer, the tests applied in diagnostics, and the treatment process. The questionnaire comprised 42 closed-ended questions with one correct answer. A statistical analysis of all answers was carried out. RESULTS: The study group consisted of 30 men and 20 women aged 27-94 years old. A strong, statistically significant negative correlation between a patient's age and his/her awareness of the prevention and treatment of colorectal cancer was noted (p<0.001; r= -0.51). The study demonstrated a statistically significant relationship between the occurrence of neoplasms in a patient's family (p=0.009) or, more specifically, the occurrence of colorectal cancer (p=0.008), and the awareness of the prevention programme. The women's group was characterised by statistically significantly greater awareness of colonoscopy as a screening examination (p=0.004). CONCLUSIONS: Patients need more information on colorectal cancer, its risk factors, prevention, the treatment process, and postoperative care. Lack of awareness of the colorectal cancer issue can be one of the major factors contributing to the high incidence of this disease. PMID- 26812842 TI - Sclerotherapy Of Esophageal Varices In Severe Hemophilia A Patient And High Titer Inhibitor--Case Report. AB - In cirrhotic hemophilia patients bleeding from esophageal varices is a serious clinical condition due to congenital deficiency of clotting factors VIII or IX, decreased prothrombin synthesis and hypersplenic thrombocytopenia. In hemophiliac with high-titer inhibitor bypassing therapy is required with activated prothrombin complex concentrates (aPCC) or recombinant activated coagulation factor VII (rFVIIa). Doses and duration treatment with these agents following endoscopic treatment of esophageal varices have not been yet established. Authors report the first case of a severe hemophilia A patient with high titer inhibitor (40 BU) treated with repeated injection sclerotherapy. The patient was admitted with symptoms of massive esophageal variceal hemorrhage ceased with emergency sclerotherapy. Bypassing therapy was administered with aPCC at initial dose of 72.5 U/kg and then with average daily dose of 162 U/kg through 5 days. To achieved a total eradication of esophageal varices the patient was then subjected to four elective sclerotherapy procedures. Two were covered by aPCC with daily dose of 120 U/kg and 145 U/kg for 4 and 3 days respectively and the following two procedures were covered by rFVIIa with the initial dose of 116 ug/kg and the next doses of 87 ug/kg administered every 3 hours in procedure day and every 4 hours on the next two days. During all procedures excellent hemostasis was achieved and no hemorrhagic or thromboembolic complications were observed. Bypassing regimen therapy with aPCC and rFVIIa we applied have been shown to be safe and effective in this patient subjected to sclerotherapy procedures. PMID- 26812843 TI - Rare Case Report Of Mesenteric Fibromatosis. AB - Mesenteric fibromatosis is a part of the clinical-pathologic spectrum of deep fibromatoses. We report this rare case of primary mesenteric tumor that was diagnosed to be a mesenteric fibromatosis on histopathological examination. In majority of patients it may remain asymptomatic and the management of these tumors depends on histopathological examination. Postoperatively, patient was well and subsequent follow up showed normal recovery. PMID- 26812844 TI - The Use Of The Diep Flap In The Modern Reconstructive Surgery. AB - Perforator flaps are one of the most complex currently known forms of tissue reconstruction. Their discovery base based on the knowledge of many generations of scientists. The DIEP flap is used in clinical situations where there is need to reconstruct a large tissue volume. Owing to the similarity of tissue structure and skin colour, it is a flap of choice in breast reconstruction with native tissues. It has large dimensions size and a considerable volume. Its peduncle is characterised by a large diameter and significant length of vessels. Anatomical variation is low and possible to assess preoperatively. It is for these reasons that the DIEP flap is counted among the flaps of the highest clinical use. With careful planning, application of meticulous surgical technique and utilisation of the operating team's experience, the complication rate is relatively low. The current reality of medical procedure pricing makes it impossible not to mention the costs. DIEP flap breast reconstruction is apparently expensive. Breast reconstruction with implants is associated with lower initial costs, but often requires additional procedures spread over time (e.g. implant replacement, plastic surgery of the other breast), which makes the costs difficult to estimate. Costs incurred by a facility performing DIEP flap reconstruction are currently not reflected in the pricing of this procedure by the Polish National Health Fund (NFZ), which is another factor affecting the number of such surgeries performed in Poland. PMID- 26812845 TI - Letters To The Editor. PMID- 26812846 TI - Nanotechnology: a clean and sustainable technology for the degradation of pharmaceuticals present in water and wastewater. AB - Pharmaceuticals, newly recognized classes of environmental pollutants, are becoming increasingly problematic contaminants of either surface water or ground water around industrial and residential communities. Pharmaceuticals are constantly released into aquatic environments, mainly due to their widespread consumption and complicated removal in wastewater treatment plants. Heterogeneous photocatalysis appear to be one of the most destructive advanced oxidation processes (AOPs) for organic contaminants and are possible to obtain complete mineralization of organic pollutants into eco-friendly end products under visible and solar light irradiation. In this study, flower-like In2S3 hierarchical nanostructures were successfully prepared via a facile solution-phase route, using thioacetamide as both sulfur source and capping agent. X-ray diffractometry (XRD) of the flowers revealed that the cubic structure of In2S3; morphological studies examined by scanning electron microscopy (SEM) showed the synthesized In2S3 nanostructure was flower-like hierarchitecture assembled from nanoscale flakes. X-ray photoelectron spectroscopy (XPS) analysis confirmed the stoichiometry of In2S3 nanoflowers. Furthermore, the photocatalytic activity studies revealed that the prepared indium(III) sulfide(In2S3) nanoflowers exhibit an excellent photocatalytic performance, degrading rapidly the aqueous pharmaceutical solution of Lisinopril under visible light irradiation. These results suggest that In2S3 nanoflowers will be a promising candidate of photocatalyst working in thevisible light range. PMID- 26812847 TI - What works in water supply and sanitation projects in developing countries with EWB-USA. AB - The World Health Organization (WHO) reports some progress on the global problem of a lack of improved water and sanitation. Between 1990 and 2012, the number of people that gained improved access to improved drinking water reached 2.3 billion people, while the number of children that have died from diarrheal diseases has fallen from 1.5 million deaths to just above 600,000 deaths (1, 2). However, it is estimated that there are still 1.8 billion people using a fecally contaminated source of drinking water (3). In addition, 748 million people continue to lack clean water, 1 billion continue to practice open defecation, and 2.5 billion people still lack adequate sanitation (3). In response to this global issue, Engineers Without Borders USA (EWB-USA) began with a mission to build a better world through engineering projects that empower communities to meet their basic human needs and equip leaders to solve the world's most pressing challenges. Their 15,000+ members work with communities to find appropriate solutions to improve water supply, sanitation, energy, agriculture, civil works and structures. Their development approach is based on standard engineering methodology, including problem identification, assessment, alternatives analysis, implementation, and monitoring and evaluation. EWB-USA began in 2002 and currently has members working in over 40 countries around the world. The majority of their work is focused in Latin America and Africa, but their programs are expanding to Asia and the Pacific Basin. Currently, EWB-USA members are working in 17 programs in six countries, including the Philippines, Thailand, Cambodia, India, Nepal, and Fiji. Success in these programs is defined by measuring overall impact and learning from failure. Impact is measured through Standard Monitoring Indicators and learning is accomplished by documenting failures and lessons learned. Through this work, the organization has impacted 2.5 million lives through primarily water supply and sanitation projects by focusing on sustainable engineering solutions, community-education, capacity building, and appropriate technologies and local resources. PMID- 26812848 TI - E-waste interventions in Ghana. AB - Electrical and electronic waste (e-waste) has become an emerging environmental and human health problem in the world in the 21st century. Recently, the developing nations of West Africa (e.g. Ghana and Nigeria) have become a major destination for e-waste worldwide. In Ghana, the e-waste recyclers use primitive methods (mechanical shredding and open burning) to remove plastic insulation from copper cables. This technique can release highly toxic chemicals and severely affect the environment and human health if improperly managed. It is as a result of the adverse impact on human health that some interventions are being made in Ghana to reduce exposure. The present mode of recycling/dismantling, which happens at Agbogbloshie must be replaced by official receiving/recycling centers to be established. Currently, equipment to strip both large and small cables are available in the country via the Blacksmith Institute (USA) and it is expected that the e-waste workers will embrace the use of these machines. This technology will go a long way to help prevent the burning of e-waste and will be replicated in other smaller e-waste centers in the country. PMID- 26812849 TI - Creating healthy and just bioregions. AB - Dramatic changes taking place locally, regionally, globally, demand that we rethink strategies to improve public health, especially in disadvantaged communities where the cumulative impacts of toxicant exposure and other environmental and social stressors are most damaging. The emergent field of Sustainability Science, including a new bioregionalism for the 21st Century, is giving rise to promising place-based (territorially rooted) approaches. Embedded in this bioregional approach is an integrated planning framework (IPF) that enables people to map and develop plans and strategies that cut across various scales (e.g. from regional to citywide to neighborhood scale) and various topical areas (e.g. urban land use planning, water resource planning, food systems planning and "green infrastructure" planning) with the specific intent of reducing the impacts of toxicants to public health and the natural environment. This paper describes a case of bioregionally inspired integrated planning in San Diego, California (USA). The paper highlights food-water-energy linkages and the importance of "rooted" community-university partnerships and knowledge-action collaboratives in creating healthy and just bioregions. PMID- 26812850 TI - Bayesian networks in infectious disease eco-epidemiology. AB - Globally, infectious diseases are responsible for a significant burden on human health. Drivers of disease transmission depend on interactions between humans, the environment, vectors, carriers, and pathogens; transmission dynamics are therefore potentially highly complex. Research in infectious disease eco epidemiology has been rapidly gaining momentum because of the rising global importance of disease emergence and outbreaks, and growing understanding of the intimate links between human health and the environment. The scientific community is increasingly recognising the need for multidisciplinary translational research, integrated approaches, and innovative methods and tools to optimise risk prediction and control measures. Environmental health experts have also identified the need for more advanced analytical and biostatistical approaches to better determine causality, and deal with unknowns and uncertainties inherent in complex systems. In this paper, we discuss the use of Bayesian networks in infectious disease eco-epidemiology, and the potential for developing dynamic tools for public health decision-making and improving intervention strategies. PMID- 26812851 TI - Worm-free children: an integrated approach to reduction of soil-transmitted helminth infections in Central Java. AB - Among children, infections with soil-transmitted helminths (STH) can cause anemia, impaired growth, and absence from school. Sustainable control of STH infection requires that appropriate latrines be integrated with health-promotion education. We report a pilot study of the effects of a combined latrine-education intervention in Central Java, Indonesia. The participants were 99 children (3-13 years old) in two villages (intervention and control) south of Semarang city. Stool samples were collected from the children and were examined for the presence of helminth eggs. After baseline data were collected, latrines were constructed and health education was given in the intervention village. Then, in both villages, all children who had STH infection at baseline were given 400 mg of albendazole. Eight months later, follow-up stool samples were collected and examined. In both villages, 20% of the children had STH infection at baseline. At follow-up, the incidence of STH infection was much lower in the intervention village than in the control village (4.0% vs. 20.4%; p<0.02). The results of this small pilot study give some confidence that a scaled-up study involving many more children and cluster-randomization of the intervention will be feasible and could provide more conclusive evidence of the intervention's effectiveness. PMID- 26812852 TI - Mercury exposure in the work place and human health: dental amalgam use in dentistry at dental teaching institutions and private dental clinics in selected cities of Pakistan. AB - During the past two decades, mercury has come under increasing scrutiny with regard to its safety both in the general population and in occupationally exposed groups. It's a growing issue of global concern because of its adverse environmental and health impacts. Very few investigations on mercury amalgam use in the dentistry sector have been carried out in South Asia and there is little data reported on mercury contamination of indoor/outdoor air at dental sites. According to an earlier SDPI study, reported in 2013, alarmingly high mercury levels were observed in air (indoor as well as outdoor) at 11 of the 34 visited dental sites (17 dental teaching institutions, 7 general hospitals & 10 dental clinics) in five main cities of Pakistan. 88% of the sites indicated indoor mercury levels in air above the USA EPA reference level of 300 ng/m3. According to our study, carried out at 38 dental teaching institutions in 12 main cities (in Khyber Pakhtunkhwa, Punjab and Sindh provinces) of Pakistan, respondents were of the opinion that the currently offered BDS curriculum does not effectively guide outgoing dental professionals and does not provide them adequate knowledge and training about mercury/mercury amalgam and other mercury related human health and mercury waste issues. 90% of respondents supported the review and revision of the present dental curriculum offered at dental teaching institutions in the country, at the earliest. A study has also been conducted to assess the status of mercury amalgam use in private dental clinics in Gilgit, Hunza, Peshawar, Rawalpindi and Islamabad. More than 90 private dental clinics were visited and dental professionals/private clinics in-charge were interviewed during June-July, 2015. The focus areas of the study were Hg amalgam toxicity, its waste management practices and safety measures practiced among the dental practitioners. In the light of the findings described and discussed in this brief report, to safeguard public health and for the protection of environment, it is strongly recommended that since mercury amalgam use cannot be banned immediately in the country, its use may be regularized and allowed subject to use of "Amalgam Separators," "Capsulated Mercury" and "Mechanized Mixing," use of mercury amalgam be banned for children (below 12 years age) and pregnant women. The curriculum currently being taught at medical and dental colleges in the country be reviewed and revised, to ensure adequate training towards minimizing mercury exposure. PMID- 26812853 TI - Solar-driven membrane distillation demonstration in Leupp, Arizona. AB - The Navajo Nation is the largest and one of the driest Native American reservations in the US. The population in the Navajo Nation is sporadically distributed over a very large area making it extremely ineffective to connect homes to a centralized water supply system. Owing to this population distribution and the multi decadal drought prevailing in the region, over 40% of the 300,000 people living on Navajo Tribal Lands lack access to running potable water. For many people the only alternative is hauling water from filling stations, resulting in economic hardship and limited supply. A solution to this problem is a de-centralized off-grid water source. The University of Arizona and US Bureau of Reclamation's Solar Membrane Distillation (SMD), stand-alone, pilot desalination system on the Navajo Reservation will provide an off-grid source of potable water; the pilot will serve as a proximal water source, ease the financial hardships caused by the drought, and provide a model for low-cost water treatment systems in arid tribal lands. Bench-scale experiments and an earlier field prototype plant showed viable operation of a solar heated, membrane distillation (MD) system, but further optimization is required. The objectives of the Navajo pilot study are to i) demonstrate integration of solar collectors and membrane distillation, ii) optimize operational parameters, iii) demonstrate and monitor technology performance during extended duration operation, and iv) facilitate independent system operation by the Navajo Water Resources Department, including hand-over of a comprehensive operations manual for implementation of subsequent SMD systems. The Navajo SMD system is designed as a perennial installation that includes remote communication of research data and full automation for remote, unmanned operation. PMID- 26812854 TI - Funisitis is more common in cervical insufficiency than in preterm labor and preterm premature rupture of membranes. AB - OBJECTIVE: To compare the frequency of histologic chorioamnionitis and funisitis among women experiencing preterm labor, preterm premature rupture of membranes (PROM) and cervical insufficiency. METHODS: This retrospective cohort study included singleton pregnant women who delivered at <=36 weeks of gestation. The patients with preterm birth were subdivided into preterm labor (n=117), preterm PROM (n=153), and cervical insufficiency (n=20). All placentas were examined for pathology, according to the criteria of Salafia with minor modification. Frequencies of histologic chorioamnionitis and funisitis were evaluated according to the causes of preterm birth. RESULTS: 1) Histologic chorioamnionitis was diagnosed in 48.7% (57/117) of cases with preterm labor, 47.4% (73/153) with preterm PROM, and 75.0% (15/20) with cervical insufficiency. Funisitis was detected in 11.1% (13/117) of cases with preterm labor, 15.7% (24/153) with preterm PROM, and 40.0% (8/20) with cervical insufficiency. 2) Frequency of histologic chorioamnionitis was higher in cases with cervical insufficiency compared to preterm PROM. Frequency of funisitis was higher in cases with cervical insufficiency compared to both preterm labor and preterm PROM (P<0.05). The difference in frequency of funisitis remained significant after adjustment for gestational age at delivery and cervical dilatation at diagnosis. 3) Frequency of grade 2 funisitis was higher in cases with cervical insufficiency (35.0%, 7/20) compared to both preterm labor (6.8%, 8/117) and preterm PROM (9.8%, 15/153) (P=0.001). And the difference remained significant after adjustment for gestational age at delivery and cervical dilatation at diagnosis. CONCLUSION: The highest frequency of funisitis was observed in cervical insufficiency among cases with spontaneous preterm birth. PMID- 26812856 TI - Out-of-hospital births in the United States 2009-2014. AB - OBJECTIVE: To evaluate recent trends of out-of-hospital births in the US from 2009 to 2014. METHODS: We accessed data for all live births occurring in the US from the National Vital Statistics System, Natality Data Files for 2009-2014 through the interactive data tool, VitalStats. RESULTS: Out-of-hospital (OOH) births in the US increased from 2009 to 2014 by 80.2% from 32,596 to 58,743 (0.79%-1.47% of all live births). Home births (HB) increased by 77.3% and births in freestanding birthing centers (FBC) increased by 79.6%. In 2014, 63.8% of OOH births were HB, 30.7% were in FBC, and 5.5% were in other places, physicians offices, or clinics. The majority of women who had an OOH birth in 2014 were non Hispanic White (82.3%). About in one in 47 non-Hispanic White women had an OOH in 2014, up from 1 in 87 in 2009. Women with a HB were older compared to hospital births (age >=35: 21.5% vs. 15.4%), had a higher live birth order(>=5: 18.9% vs. 4.9%), 3.48% had infants <2500 g and 4.66% delivered <37 weeks' gestation. 4.34% of HB were patients with prior cesarean deliveries, 1.6% were breech, and 0.81% were twins. CONCLUSIONS: Since 2004 the number of women delivered out of the hospital, at home and in freestanding birthing centers has significantly increased in the US making it the country with the most out of hospital births among all developed countries. The root cause of the increase in planned OOH births should be identified and addressed by the medical community. PMID- 26812855 TI - Omega-3 fatty acids modulate neonatal cytokine response to endotoxin. AB - Neonatal immune response is characterized by an uncompensated pro-inflammatory response that can lead to inflammation-related morbidity and increased susceptibility to infection. We investigated the effects of long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) pre-treatment on cytokine secretion to low concentration endotoxin (lipopolysaccharide, LPS) in THP-1 monocytes and neonatal cord blood (CB) from healthy full-term infants. Pre-treatment of THP-1 cells, with either n-3 PUFA at 25 or 100 MUM significantly reduced IL-6, IL-10, and IL 12 secretion while DHA, but not EPA, reduced TNF-alpha response to LPS. DHA inhibition was stronger compared to EPA and effective at the low concentration. The same concentrations of n-3 PUFAs inhibited IL-12 but not IL-10 cytokine response in whole CB from 9 infants pre-treated for 24 h. To assess clinical relevance for acute response to LPS, the effects of low-concentration DHA at 25 MUM or 12.5 MUM were assessed before and after LPS exposure of isolated CB mononuclear cells from 20 infants for 1 h. When added before or after LPS, physiologic DHA treatment produced significant concentration-dependent inhibition of TNF-alpha, IL-6, IL-1beta, and IL-8 secretion. The results demonstrate prophylactic and therapeutic modulation of neonatal cytokine response to LPS and provide proof-of-concept that low-concentration administration of n-3 PUFA could attenuate or resolve neonatal inflammatory response. PMID- 26812857 TI - Male Iranian adolescent's reasons for having an other-gender friend. AB - AIM: The aim of this study was to identify the primary reasons why male Iranian adolescents enter into other-gender friendships. METHODS: A qualitative study was conducted with a sample of 21 male adolescents recruited in public places in Tehran, Iran. Information about each boy's experiences with other-gender friends was collected via semi-structured interviews whose contents were analyzed with a conventional qualitative content analysis approach. RESULTS: Five reasons were identified for engaging in other-gender friendships: (a) for the purpose of entertainment, (b) financial benefits, (c) increased popularity with peers, (d) sensation seeking and (e) sexual experiences. CONCLUSION: This study revealed that adolescent males do not follow appropriate goals for communicating with the other-gender. In many cases, these goals could endanger their own health and the health of their other-gender friends. Future researchers must focus on identifying and understanding the factors that influence an adolescent to enter into an other-gender friendship. PMID- 26812858 TI - Characterization of eating behavior disorders in school-aged children and adolescents: a population-based study. AB - OBJECTIVE: Cross-sectional study to assess the characteristics of the risk behaviors for eating disorders (EDs) in school children between 10 and 14 years of age in the city of Recife, Pernambuco, Brazil. METHODS: 1405 school-aged children were assessed, using the Eating Behaviours and Body Image Test (EBBIT) to screen for EDs. The normality of the continuing variables was tested using the Kolmogorov-Smirnov test with Lilliefors correction. They were described as medians and interquartile intervals (25 and 75th percentiles). RESULTS: The criteria that represented a condition of anorexia and/or bulimia nervosa were considered as strong indicators of risk for EDs in school-aged children who indicated the following behaviors with scores superior to the 75th percentile on the scales: "compulsive eating" 3.0% (CI95% 2.2-4.0); "dissatisfaction with body image/restrictive eating" 1.3% (CI95% 0.8-2.0); children scoring superior to the 30th percentile, "compulsive eating" + "dissatisfaction with body image/restrictive eating", 0.6% (CI95% 0.3-1.2); and superior to the 50th percentile; "compensatory behavior for hyperphagia" 6.7% (CI95% 5.4-8.1). In addition, greater vulnerability of the female gender was perceived, as well as an increase in the preliminary risk factors of EDs, such as advanced age, dissatisfaction with the body image linked to restrictive behaviors and the compulsive establishment of an eating pattern. CONCLUSION: This study shows the dimension of the problem in this ecological context and the urgent need for intervention programs, developed among different sectors, from the perspective of the adolescents' empowerment to prevent and minimize the vulnerability factors of the eating disorders. PMID- 26812859 TI - Adolescent's perceptions of parental influences on physical activity. AB - BACKGROUND: Youth physical activity engagement is a key component of contemporary health promotion strategies. Parents have potential to influence the physical activity behaviours of their children. The purpose of this study was to explore associations between adolescent self-reported physical activity, parent physical activity and perceptions of parental influence as measured by the Children's Physical Activity Correlates (CPAC) questionnaire. METHODS: This investigation included a total of 146 adolescents and their parents. Self-reported measures of physical activity were obtained using the International Physical Activity Questionnaire for Adolescents and International Physical Activity Questionnaire for adolescents and their parents respectively. Adolescent perceptions of parental role modelling, support, and encouragement were measured with the parental influences scales of the CPAC. RESULTS: Ordinary least squares regression indicated that perceptions of parental role modelling (beta=197.41, 95% CI 34.33-360.49, p=0.031) was positively associated with adolescent self reported moderate-to-vigorous physical activity with the overall model accounting for a small amount of the variance (R2=0.076). CONCLUSION: These results are in agreement with previous research indicating that parents play a small, albeit vital role in the physical activity engagement of their children. Public health campaigns with the aim of promoting youth physical activity should endeavour to incorporate parents into their interventions. PMID- 26812860 TI - Youth friendly health services in a rural community of Lagos, Nigeria: are the youths receptive? AB - BACKGROUND: Globally, the youths constitute a major segment of most societies particularly in developing countries. This study was undertaken to assess the perception and practices related to youth friendly health services (YFHS) by in school adolescents in a rural community of Lagos, Nigeria. METHODS: A descriptive cross-sectional survey was conducted on 400 proportionately selected consenting respondents from the senior classes of the three secondary schools in Agbowa community. A pre-tested interviewer-administered questionnaire was used for data collection and analysis was done with the aid of statistical software. RESULTS: Most of the respondents were in the age range of 12-15 years with mean age being 15.33+/-1.54 years. About half (46.8%) of the respondents correctly described adolescents as persons between the ages of 10 and 19 years. The majority (83.2%) of the respondents first heard about the Youth Friendly Health facilities from parents, guardians and friends. However, only few of the respondents had ever visited a Youth Friendly Center. A good location, convenient hours and comfortable surroundings were the most appealing aspects of YFHS. The provision of a seminar room and educational materials (60.8% and 70.8%, respectively) are important to the respondents. Reproductive health (56.8%) was the most preferred health education topic chosen by the respondents. CONCLUSION: Sensitization of the youths in the Agbowa community about youth friendly health services and provision of such services would be useful in reducing risky practices and improving their health. PMID- 26812861 TI - Parathyroid hormone-ionized calcium dynamics over the first year of life. AB - BACKGROUND: Ionized calcium (iCa) is believed to be the principle determinant of parathyroid hormone concentration (PTH). However, previous studies contained few infants. METHODS: This ancillary study from our vitamin D3 dose-response trial in healthy, breastfed infants measured calcium, phosphorus, PTH and 25(OH)D (25 hydroxyvitamin D) at 1, 2, 3, 6, 9 and 12 months of age. The relationship between iCa and PTH was assessed by Pearson correlation and a mixed effects regression model to account for repeated measures. RESULTS: No significant correlations were observed between iCa and PTH at individual visits (p>0.2). After accounting for repeated measures, PTH decreased with increasing iCa (slope -5.25; 95% confidence intervals (CI) -8.78 to -1.73), decreased with increasing 25(OH)D (slope -0.006; 95% CI -0.009 to -0.002, and increased with later visits (6-12 months, p<0.001), CONCLUSIONS: We observed a weak negative relationship between iCa and PTH and an increase with age consistent with physiologic maturation. PMID- 26812862 TI - Increased levels of bisphenol A (BPA) in Thai girls with precocious puberty. AB - BACKGROUND: Reports on the secular trend of pubertal onset indicate a recent earlier start especially in girls. Bisphenol A (BPA), which posses estrogenic activity, might be a cause of advanced puberty. The objective of the study was to determine the association between BPA and advanced puberty. METHODS: A cross sectional study was conducted in patients with advanced puberty (n=41) compared to age-matched controls (n=47). Anthropometric measurements, estradiol, basal and gonadotropin releasing hormone (GnRH)-stimulated follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels, uterine sizes, ovarian diameters and bone ages were obtained. Urinary BPA concentrations were analyzed by ultra performance liquid chromatography-tandem mass spectrometry (UPLC/MSMS) with the lower limit of quantification (LLOQ) of 0.05 ng/mL. RESULTS: The median adjust BPA concentration in advanced puberty group was higher than in control groups [1.44 vs. 0.59 MUg/g creatinine (Cr): p<0.05]. We also found that the median adjust-BPA concentration in girls with advanced puberty who were overweight/obese, was greater than in the normal pubertal overweight/obese girls (1.74 vs. 0.59 MUg/g Cr: p<0.05), and was in the same trend among normal weight girls with advanced and normal puberty (0.83 vs. 0.49 MUg/g Cr: p=0.09), but not statistically significant. CONCLUSIONS: The present findings suggest that BPA exposure appears to be related to an earlier age at onset of puberty especially in obese girls. PMID- 26812863 TI - Putative duality of presynaptic events. AB - The main structure in the brain responsible not only for nerve signal transmission but also for its simultaneous regulation is chemical synapse, where presynaptic nerve terminals are of considerable importance providing release of neurotransmitters. Analyzing transport of glutamate, the major excitatory neurotransmitter in the mammalian CNS, the authors suggest that there are two main relatively independent mechanisms at the presynaptic level that can influence the extracellular glutamate concentration, and so signaling, and its regulation. The first one is well-known precisely regulated compound exocytosis of synaptic vesicles containing neurotransmitters stimulated by membrane depolarization, which increases significantly glutamate concentration in the synaptic cleft and initiates glutamate signaling through postsynaptic glutamate receptors. The second one is permanent glutamate turnover across the plasma membrane that occurs without stimulation and is determined by simultaneous non pathological transporter-mediated release of glutamate thermodynamically synchronized with uptake. Permanent glutamate turnover is responsible for maintenance of dynamic glutamatein/glutamateout gradient resulting in the establishment of a flexible extracellular level of glutamate, which can be unique for each synapse because of dependence on individual presynaptic parameters. These two mechanisms, i.e. exocytosis and transporter-mediated glutamate turnover, are both precisely regulated but do not directly interfere with each other, because they have different intracellular sources of glutamate in nerve terminals for release purposes, i.e. glutamate pool of synaptic vesicles and the cytoplasm, respectively. This duality can set up a presynaptic base for memory consolidation and storage, maintenance of neural circuits, long-term potentiation, and plasticity. Arguments against this suggestion are also considered. PMID- 26812864 TI - Recent approaches and challenges in iPSCs: modeling and cell-based therapy of Alzheimer's disease. AB - The lack of effective therapies for different neurodegenerative disorders has placed huge burdens on society. To overcome the restricted capacity of the central nervous system for regeneration, the promising alternative would be to use stem cells for more effective treatment of chronic degenerative and inflammatory neurological conditions and also of acute neuronal damage and from injuries or cerebrovascular diseases. The generation of induced pluripotent stem cells from somatic cells by the ectopic expression of specific transcription factors has provided the regenerative medicine field with a new tool for investigating and treating neurodegenerative diseases, including Alzheimer's disease (AD). This technology provides an alternative to traditional approaches, such as nuclear transfer and somatic cell fusion using embryonic stem cells. However, due to a problem in standardization of certain reprogramming techniques and systems research, the induced pluripotent stem cell-based technology is still in its infancy. The present paper is aimed at a brief review of the current status in modeling and cell-based therapies for AD. PMID- 26812865 TI - Intrahemispheric white matter asymmetries: the missing link between brain structure and functional lateralization? AB - Hemispheric asymmetries are a central principle of nervous system architecture and shape the functional organization of most cognitive systems. Structural gray matter asymmetries and callosal interactions have been identified as contributing neural factors but always fell short to constitute a full explanans. Meanwhile, recent advances in in vivo white matter tractography have unrevealed the asymmetrical organization of many intrahemispheric white matter pathways, which might serve as the missing link to explain the substrate of functional lateralization. By taking into account callosal interactions, gray matter asymmetries and asymmetrical interhemispheric pathways, we opt for a new triadic model that has the potential to explain many observations which cannot be elucidated within the current frameworks of lateralized cognition. PMID- 26812866 TI - Evaluation of antinociceptive and anti-inflammatory properties of methanolic crude extract of Lophopetalum javanicum (bark). AB - BACKGROUND: The aim of the current study was to investigate the scientific basis of the traditional application of Lophopetalum javanicum for measuring anti inflammatory and analgesic activity and phytochemical screening. METHODS: Present study includes the preliminary screening of the phytochemical composition and in vivo analgesic and anti-inflammatory activity of methanolic extract of L. javanicum (MELJ). Hot-plate test and tail immersion method were used to investigate acute analgesic effects of L. javanicum, and the potency in inhibition of chronic inflammation in mice was tested by carrageenan-induced paw edema and formalin-induced edema method. RESULTS: One hour after the administration of carrageenan, rat's paw was inflamed, and after treating it with 500 mg/kg dose, increase in the significant inhibitory effect on paw was observed. At the third hour after carrageenan injection, extreme inhibition (55.61%+/-0.015%; p<0.001) resulted by methanolic extract. By using hot plate method, it was found that L. javanicum increases pain tolerance time up to 17.89+/-0.079 min, whereas the compared standard's interval was 21.48+/-0.397 min. In tail immersion method, the pain threshold was 3.02+/-0.074 (p<0.001) at 400 mg/kg by L. javanicum at 90 min of experiment. CONCLUSIONS: This study manifested that the methanolic extract of L. javanicum is efficient in inhibiting pain mediators to release, and conceivably, this report should get priority while searching for a new analgesic and anti-inflammatory agent. PMID- 26812867 TI - Prevalence, risk factors and antimicrobial susceptibility pattern of extended spectrum beta-lactamase-producing bacteria in a tertiary care hospital. AB - BACKGROUND: The widespread misuse of antibiotics over the past several decades has been regarded as the contributing factor in the development of resistance toward them. Extended spectrum beta-lactamases (ESBLs) are enzymes produced by certain bacteria that can make them resistant to certain antibiotics. Early detection of ESBL strains and judicious use of antibiotics and proper implementation of infection control strategies are essential to prevent the spread of this threat in the community. The study aimed at appraising the prevalence, risk factors and antimicrobial susceptibility pattern of ESBL producing microorganisms. METHODS: A prospective observational study was carried out in a tertiary care referral hospital located in Malappuram district of Kerala among inpatients with infection by ESBL-producing bacteria in order to estimate the prevalence, risk factors and their antibiotic susceptibility pattern. RESULTS: Out of the total 1156 patients studied, 118 had confirmed diagnosis on the presence of ESBL-producing microorganisms. Overall, 9.79% of all samples growing Enterobacteriaceae yielded an ESBL producer. Out of the total isolates identified, 66.1% were urinary tract infections, 15.1% were respiratory tract infections, 14.4% were surgical site infections and the remaining constituted blood stream infections. The highest antimicrobial activity against ESBL producing isolates was observed for meropenem. CONCLUSIONS: High prevalence of ESBL-producing organisms is evident in the study setting implicating the necessity to report the ESBL production along with the routine sensitivity reports supplemented with control measures which can assist a clinician in prescribing appropriate antibiotics. PMID- 26812868 TI - Unguisin F, a new cyclic peptide from the endophytic fungus Mucor irregularis. AB - The new cyclic heptapeptide unguisin F (1) and the known congener unguisin E (2), were obtained from the endophytic fungus Mucor irregularis, isolated from the medicinal plant Moringa stenopetala, collected in Cameroon. The structure of the new compound was unambiguously determined on the basis of one- and two dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. The absolute configuration of the amino acid residues of 1 and 2 was determined using Marfey's analysis. Compounds 1 and 2 were evaluated for their antibacterial and antifungal potential, but failed to display significant activities. PMID- 26812869 TI - The effect of nicotine on the expressions of the alpha7 nicotinic receptor gene and Bax and Bcl-2 proteins in the mammary gland epithelial-7 breast cancer cell line and its relationship to drug resistance. AB - The binding of nicotine with nicotinic acetylcholine receptors (nAChRs) stimulates cell division and increases drug resistance in cancer. Experiments with specific inhibitors such as RNAi, hexamethonium, and alpha-bungarotoxin showed that alpha7 nicotinic receptor plays a key role in the pro-proliferation activity of nicotine. However, the mechanism of nicotine in the progress of breast cancer, the commonest malignancy in women, remains unknown. This study focuses on the effect of nicotine on the expressions of the alpha7 nicotinic receptor gene and Bax and Bcl-2 proteins in mammary gland epithelial-7 (MCF-7) breast cancer cells and its relationship to drug resistance. To evaluate the effect on drug resistance, human mammary gland epithelial adenocarcinomas from the MCF-7 line were exposed to 100 MUl of nicotine at a concentration of 9.2 mg/ml for varying periods of time. Then, the cells were treated with 1, 2, 3 or 5 MUl/ml of doxorubicin, either with or without the continued presence of nicotine. Cell viability was determined using the MTT assay. The biochemical parameters of apoptosis, including the expressions of Bax, Bcl-2 and alpha7 nicotinic receptor proteins were determined via western blotting, and the alpha7 nicotinic receptor gene expression level was assessed via real-time qPCR using the 2(-DeltaDeltaCt) method. Differences in the target gene expression levels were evaluated with ANOVA with p <= 0.05 considered significant. We found a novel and effective signaling pathway of nicotine in the MCF-7 breast cancer cell line. The levels of alpha7 nicotinic receptor and Bcl-2 protein increased but the Bax protein levels decreased, while the alpha7 nicotinic receptor gene expression level was not significantly different compared with the control. PMID- 26812870 TI - On the regulative role of the glutamate receptor in mitochondria. AB - The purpose of this work was to study the regulative role of the glutamate receptor found earlier in the brain mitochondria. In the present work a glutamate dependent signaling system with similar features was detected in mitochondria of the heart. The glutamate-dependent signaling system in the heart mitochondria was shown to be suppressed by gamma-aminobutyric acid (GABA). The GABA receptor presence in the heart mitochondria was shown by golding with the use of antibodies to alpha- and beta-subunits of the receptor. The activity of glutamate receptor was assessed according to the rate of synthesis of hydrogen peroxide. The glutamate receptor in mitochondria could be activated only under conditions of hypoxic stress, which in model experiments was imitated by blocking Complex I by rotenone or fatty acids. The glutamate signal in mitochondria was shown to be calcium- and potential-dependent and the activation of the glutamate cascade was shown to be accompanied by production of hydrogen peroxide. It was discovered that H2O2 synthesis involves two complexes of the mitochondrial electron transfer system - succinate dehydrogenase (SDH) and fatty acid dehydrogenase (ETF:QO). Thus, functions of the glutamate signaling system are associated with the system of respiration-glycolysis switching (the Pasteur-Crabtree) under conditions of hypoxia. PMID- 26812871 TI - Corrigendum to: Defects of corneocyte structural proteins and epidermal barrier in atopic dermatitis. PMID- 26812872 TI - New mutations in SERPING1 gene of Brazilian patients with hereditary angioedema. AB - Hereditary Angioedema is an autosomal dominant inherited disease leading to oedema attacks with variable severity and localization predominantly caused by C1 INH deficit. More than 400 mutations have been already identified, however no genetic analysis of a Brazilian cohort of HAE patients with C1-INH deficiency has been published. Our aim was to perform genetic analysis of C1-INH gene (SERPING1) in Brazilian HAE patients. We screened the whole SERPING1 coding region from 30 subjects out of 16 unrelated families with confirmed diagnosis of HAE due to C1 INH deficiency. Clinical diagnosis was based on symptoms and quantitative and/or functional analysis of C1-INH. We identified fifteen different mutations among which eight were not previously described according to databases. We found five small deletions (c.97_115del19; c.553delG; c.776_782del7; c.1075_1089del15 and c.1353_1354delGA), producing frameshifts leading to premature stop codons; seven missense mutations (c.498C>A; c.550G>C; c.752T>C; c.889G>A; c.1376C>A; c.1396C>T; c.1431C>A); one nonsense mutation (c.1480C>T), and two intronic alterations (c.51+1G>T; c.51+2T>C). Despite the small number of participants in this study, our results show mutations not previously identified in SERPING1 gene. This study represents the first Brazilian HAE cohort evaluated for mutations and it introduces the possibility to perform genetic analysis in case of need for differential diagnosis. PMID- 26812873 TI - Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA). AB - Daratumumab is a fully human anti-CD38 IgG1-kappa monoclonal antibody (mAb) currently being evaluated in several Phase 2 and 3 clinical studies for the treatment of multiple myeloma (MM). In this clinical case study we demonstrate that daratumumab can be detected as an individual monoclonal band in serum immunofixation electrophoresis (IFE). M-protein follow-up by IFE is part of the International Myeloma Working Group (IMWG) criteria to assess treatment response. Therefore, it is crucial that the daratumumab band is not confused with the endogenous M-protein of the patient during IFE interpretation. Moreover, a significant number of IgG-kappa M-proteins co-migrate with daratumumab. Co migration introduces a bias in the M-protein quantification since pharmacokinetic studies show that daratumumab peak plasma concentrations reach up to 1 g/L. More importantly, co-migration can mask clearance of the M-protein by IFE which is necessary for classification of complete response by IMWG criteria (negative serum IFE). For optimal M-protein monitoring the laboratory specialist needs to be informed when patients receive daratumumab, and it is essential that the laboratory specialist is aware that a slow migrating band in the gamma-region in those patients may be derived from the daratumumab. A daratumumab specific IFE reflex assay (DIRA) has been developed and can be utilized to abrogate interference. The here described mAb interference is not limited to daratumumab, and as therapeutic antibodies gain approval and enter into common clinical practice, laboratory specialists will need additional processes to characterize IFE interference and distinguish endogenous M-protein from therapeutic antibodies. PMID- 26812874 TI - Prognostic value of red blood cell distribution width in acute pancreatitis patients admitted to intensive care units: an analysis of a publicly accessible clinical database MIMIC II. PMID- 26812876 TI - Measurement of free light chains - pros and cons of current methods. AB - The measurement of the serum free light chains (FLC) is of paramount importance in the management of patients with plasma cell dyscrasias (PSD). The immunoassays for FLC measurement require adequate precision, accuracy, specificity and reproducibility between batches to prevent under or over estimation of FLC concentration and for an adequate patient monitoring. Considering the peculiarity of the measurand (monoclonal proteins), the optimization of any analytical aspect is difficult to achieve. Three methods are currently available for the assay. The first one has been on the market for over 15 years, and it is based on polyclonal antibodies. The vast majority of the clinical studies demonstrating the utility of the serum FLC measurement have been performed using this assay. A second method based on monoclonal antibodies (mAbs) was marketed in 2011; a third one, also employing mAbs and allowing the simultaneous measurement of kappa and lambda FLC is in the process of publication. These methods show relevant differences in the type of antibodies used and in the assay design and it is not possible to identify an immunoassay that is superior to the others in any analytical aspect. The comparison studies show that the three methods differ significantly in terms of quantitative values, especially when samples containing monoclonal proteins are compared. Hence the methods cannot be used interchangeably, in particular when the assay is used to monitor the patient response to therapy. In the absence of an international standard for FLC measurement, it is impossible, at this stage to establish, which method shows the best accuracy. PMID- 26812875 TI - Monoclonal antibody therapeutics as potential interferences on protein electrophoresis and immunofixation. AB - BACKGROUND: The use of therapeutic recombinant monoclonal antibodies (mAbs) has triggered concerns of mis-diagnosis of a plasma cell dyscrasia in treated patients. The purpose of this study is to determine if infliximab (INF), adalimumab (ADA), eculizumab (ECU), vedolizumab (VEDO), and rituximab (RITU) are detected as monoclonal proteins by serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE). METHODS: Pooled normal sera were spiked with various concentrations (ranging from trough to peak) of INF, ADA, ECU, VEDO and RITU. The peak concentration for VEDO and RITU was also added to samples with known monoclonal gammopathies. All samples were analyzed by SPEP (Helena Laboratories) and IFE (Sebia); sera containing peak concentrations of mAbs were reflexed to electrospray-time-of-flight mass spectrometry (AbSciex Triple TOF 5600) for the intact light chain monoclonal immunoglobulin rapid accurate mass measurement (miRAMM). RESULTS: For all mAbs tested, no quantifiable M-spikes were observed by SPEP at any concentration analyzed. Small gamma fraction abnormalities were noted on SPEP for VEDO at 300 MUg/mL and RITU at 400 MUg/mL, with identification of small IgG kappa proteins on IFE. Using miRAMM for peak samples, therapeutic mAbs light chain accurate masses were identified above the polyclonal background and were distinct from endogenous monoclonal gammopathies. CONCLUSIONS: MAbs should not be easily confounded with plasma cell dyscrasias in patients undergoing therapy except when a SPEP and IFE are performed within a couple of days from infusion (peak). In ambiguous cases the use of the miRAMM technology could precisely identify the therapeutic mAb distinct from any endogenous monoclonal protein. PMID- 26812877 TI - Dydrogesterone and the immunology of pregnancy. AB - Progesterone is indispensable for the maintenance of pregnancy, both via its endocrine effects and its role in creating a favorable immunological environment for the fetus. This review focuses on the immunological effects of progesterone. Progestogens have been shown to have very interesting effects on cytokine production and decidual natural killer (NK) cell activity. The orally administered progestogen, dydrogesterone, has the ability to modulate cytokine production patterns in a manner that could be conducive to successful pregnancy. The adverse effects of progesterone deficiency and the beneficial effects of progesterone supplementation in pregnancy pathologies will be discussed. PMID- 26812878 TI - Sexuality in eating disorders patients: etiological factors, sexual dysfunction and identity issues. A systematic review. AB - The scientific community appears to be less interested in sexuality of eating disorders (EDs) as compared to other psychiatric or medical comorbidities. However, a clear association between sexual problems and ED psychopathology was reported from different perspectives. The overarching goal of this systematic review was to evaluate the general approach of the scientific literature toward the topic of sexuality and EDs. In particular, four different categories of research have been individuated, encompassing the role of puberty, and sexual abuse in the pathogenesis of the disorders, sexual dysfunctions, and the association between sexual orientation and EDs psychopathology. Timing of puberty with its hormonal consequences and the changes in the way persons perceive their own body represent a crucial period of life for the onset of the disorder. Sexual abuse, and especially childhood sexual abuse are well-recognized risk factors for the development of ED, determining a worse long-term outcome. Recent research overcome the approach that considers sexual activity of EDs patients, in terms of hypersexuality and dangerous sexual behaviors, considering the sexuality of EDs persons in terms of sexual desire, satisfaction, orgasm and pain. Results from this line of research are promising, and describe a clear relationship between sexual dysfunction and the core psychopathological features of EDs, such as body image disturbances. Finally, the analysis of the literature showed an association between sexual orientation and gender dysphoria with EDs psychopathology and pathological eating behaviors, confirming the validity of research developing new models of maintaining factors of EDs related to the topic of self-identity. PMID- 26812879 TI - Pathophysiology of obesity on knee joint homeostasis: contributions of the infrapatellar fat pad. AB - Osteoarthritis (OA) is a debilitating condition characterized by inflammation, breakdown, and consequent loss of cartilage of the joints. Epidemiological studies indicate obesity is an important risk factor involved in OA initiation and progression. Traditional views propose OA to be a biomechanical consequence of excess weight on weight-bearing joints; however, emerging data demonstrates that systemic and local factors released from white adipose depots play a role. Hence, current views characterize OA as a condition exacerbated by a metabolic link related to adipose tissue, and not solely related to redistributed/altered weight load. Factors demonstrated to influence cartilage and bone homeostasis include adipocyte-derived hormones ("adipokines") and adipose depot released cytokines. Epidemiological studies demonstrate a positive relation between systemic circulating cytokines, leptin, and resistin with OA types, while the association with adiponectin is controversial. Local factors in joints have also been shown to play a role in OA. In particular, this includes the knee, a weight bearing joint that encloses a relatively large adipose depot, the infrapatellar fat pad (IFP), which serves as a source of local inflammatory factors. This review summarizes the relation of obesity and OA as it specifically relates to the IFP and other integral supporting structures. Overall, studies support the concept that metabolic effects associated with systemic obesity also extend to the IFP, which promotes inflammation, pain, and cartilage destruction within the local knee joint environment, thus contributing to development and progression of OA. PMID- 26812880 TI - Model approach for stress induced steroidal hormone cascade changes in severe mental diseases. AB - INTRODUCTION: Stress was described by Cushing and Selye as an adaptation to a foreign stressor by the anterior pituitary increasing ACTH, which stimulates the release of glucocorticoid and mineralocorticoid hormones. The question is raised whether stress can induce additional steroidal hormone cascade changes in severe mental diseases (SMD), since stress is the common denominator. METHODS: A systematic literature review was conducted in PubMed, where the steroidal hormone cascade of patients with SMD was compared to the impact of increasing stress on the steroidal hormone cascade (a) in healthy amateur marathon runners with no overtraining; (b) in healthy well-trained elite soldiers of a ranger training unit in North Norway, who were under extreme physical and mental stress, sleep deprivation, and insufficient calories for 1 week; and, (c) in soldiers suffering from post traumatic stress disorder (PTSD), schizophrenia (SI), and bipolar disorders (BD). RESULTS: (a) When physical stress is exposed moderately to healthy men and women for 3-5 days, as in the case of amateur marathon runners, only few steroidal hormones are altered. A mild reduction in testosterone, cholesterol and triglycerides is detected in blood and in saliva, but there was no decrease in estradiol. Conversely, there is an increase of the glucocorticoids, aldosterone and cortisol. Cellular immunity, but not specific immunity, is reduced for a short time in these subjects. (b) These changes are also seen in healthy elite soldiers exposed to extreme physical and mental stress but to a somewhat greater extent. For instance, the aldosterone is increased by a factor of three. (c) In SMD, an irreversible effect on the entire steroidal hormone cascade is detected. Hormones at the top of the cascade, such as cholesterol, dehydroepiandrosterone (DHEA), aldosterone and other glucocorticoids, are increased. However, testosterone and estradiol and their metabolites, and other hormones at the lower end of the cascade, seem to be reduced. 1) The rate and extent of reduction of the androgen metabolites may cause a decrease of cellular and specific immunity which can lead to viral and bacterial infections; joint and stomach inflammation; general pain; and allergic reactions. 2) The decrease in testosterone, and estradiol in SMD may have detrimental effects in cell repair as the estradiol metabolite, 2-methoxy estradiol (2ME2), helps to transforms stem cells into functional cells. As dopamine and 2ME2 are inversely metabolized via various forms of catechol-O methyl transferase (COMT), well-being and hypertension may be related. 2ME2 is related to vascular endothelial growth factor (VEGF), which regulates blood capillary growth and O2 supply. As reduced O2 is a key marker of stress, the increase of glucocorticoids in all forms of mental and physical stress cannot counterbalance the reduced 2ME2 in cellular and mental stress. The increased cholesterol and triglycerides are related to stroke and infarction, contributing to a reduced life expectancy in SMD between 14 and 20 years. The increase of aldosterone leads to increases in anxiety, edema, and lung infections. DISCUSSION: Increasing mental and physical stress is related to systematic deviations in the steroidal hormone cascade in the non-psychotic state, which then may cause life threatening co-morbidities in PTSD, SI, and BD. PMID- 26812881 TI - Hydroxyurea synergizes with valproic acid in wild-type p53 acute myeloid leukaemia. AB - Palliative care in acute myeloid leukaemia (AML) is inadequate. For elderly patients, unfit for intensive chemotherapy, median survival is 2-3 months. As such, there is urgent demand for low-toxic palliative alternatives. We have repositioned two commonly administered anti-leukaemia drugs, valproic acid (VPA) and hydroxyurea (HU), as a combination therapy in AML. The anti-leukemic effect of VPA and HU was assessed in multiple AML cell lines confirming the superior anti-leukemic effect of combination therapy. Mechanistic studies revealed that VPA amplified the ability of HU to slow S-phase progression and this correlated with significantly increased DNA damage. VPA was also shown to reduce expression of the DNA repair protein, Rad51. Interestingly, the tumour suppressor protein p53 was revealed to mitigate cell cycle recovery following combination induced arrest. The efficacy of combination therapy was validated in vivo. Combination treatment increased survival in OCI-AML3 and patient-derived xenograft mouse models of AML. Therapy response was confirmed by optical imaging with multiplexed near-infrared labelled antibodies. The combination of HU and VPA indicates significant potential in preclinical models of AML. Both compounds are widely available and well tolerated. We believe that repositioning this combination could significantly enhance the palliative care of patients unsuited to intensive chemotherapy. PMID- 26812882 TI - Genomic loss of EZH2 leads to epigenetic modifications and overexpression of the HOX gene clusters in myelodysplastic syndrome. AB - The role of EZH2 in cancer is complex and may vary depending on cancer type or stage. We examined the effect of altered EZH2 levels on H3K27 methylation, HOX gene expression, and malignant phenotype in myelodysplastic syndrome (MDS) cell lines and an in vivo xenograft model. We also studied links between EZH2 expression and prognosis in MDS patients. Patients with high-grade MDS exhibited lower levels of EZH2 expression than those with low-grade MDS. Low EZH2 expression was associated with high percentages of blasts, shorter survival, and increased transformation of MDS into acute myeloid leukemia (AML). MDS patients frequently had reductions in EZH2 copy number. EZH2 knockdown increased tumor growth capacity and reduced H3K27me3 levels in both MDS-derived leukemia cells and in a xenograft model. H3K27me3 levels were reduced and HOX gene cluster expression was increased in MDS patients. EZH2 knockdown also increased HOX gene cluster expression by reducing H3K27me3, and H3K27 demethylating agents increased HOX gene cluster expression in MDS-derived cell lines. These findings suggest genomic loss of EZH2 contributes to overexpression of the HOX gene clusters in MDS through epigenetic modifications. PMID- 26812883 TI - Transcriptional profiling analysis and functional prediction of long noncoding RNAs in cancer. AB - Long noncoding RNAs (lncRNAs), which are noncoding RNAs (ncRNAs) with length more than 200 nucleotides (nt), have been demonstrated to be involved in various types of cancer. Consequently, it has been frequently discussed that lncRNAs with aberrant expression in cancer serve as potential diagnostic biomarkers and therapeutic targets. However, one major challenge of developing cancer biomarkers is tumor heterogeneity which means that tumor cells show different cellular morphology, metastatic potential as well as gene expression. In this study, a custom designed microarray platform covering both mRNAs and lncRNAs was applied to tumor tissues of gastric, colon, liver and lung. 316 and 157 differentially expressed (DE-) protein coding genes and lncRNAs common to these four types of cancer were identified respectively. Besides, the functional roles of common DE lncRNAs were inferred based on their expression and genomic position correlation with mRNAs. Moreover, mRNAs and lncRNAs with tissue specificity were also identified, suggesting their particular roles with regard to specific biogenesis and functions of different organs. Based on the large-scale survey of mRNAs and lncRNAs in four types of cancer, this study may offer new biomarkers common or specific for various types of cancer. PMID- 26812884 TI - Expression of aquaporin1, a water channel protein, in cytoplasm is negatively correlated with prognosis of breast cancer patients. AB - Aquaporin1 (AQP1) belongs to a highly conserved family of aquaporin proteins which facilitate water flux across cell membranes. Although emerging evidences indicated the cytoplasm was important for AQP1 localization, the function of AQP1 corresponding to its cytoplasmic distribution has rarely been explored until present. In our clinical study, we reported for the first time that AQP1 was localized dominantly in the cytoplasm of cancer cells of invasive breast cancer patients and cytoplasmic AQP1 was an independent prognostic factor. High expression of AQP1 indicated a shorter survival, especially in luminal subtype. Moreover, in line with our findings in clinic, cytoplasmic expression of AQP1 was further validated in both primary cultured breast cancer cells and AQP1 over expressing cell lines, in which the functional importance of cytoplasmic AQP1 was confirmed in vitro. In conclusion, our study provided the first evidence that cytoplasmic expression of AQP1 promoted breast cancer progression and it could be a potential prognostic biomarker for breast cancer. PMID- 26812885 TI - CDK9 inhibitors selectively target estrogen receptor-positive breast cancer cells through combined inhibition of MYB and MCL-1 expression. AB - Our previous studies showed that MYB is required for proliferation of, and confers protection against apoptosis on, estrogen receptor-positive (ER(+ve)) breast cancer cells, which are almost invariably also MYB(+ve). We have also shown that MYB expression in ER(+ve) breast cancer cells is regulated at the level of transcriptional elongation and as such, is suppressed by CDK9i. Here we examined the effects of CDK9i on breast cancer cells and the involvement of MYB in these effects. ER(+ve) breast cancer cell lines including MCF-7 were much more sensitive (> 10 times) to killing by CDK9i than ER(-ve)/MYB(-ve) cells. Moreover, surviving cells showed a block at the G2/M phase of the cell cycle. Importantly, ectopic MYB expression conferred resistance to apoptosis induction, cell killing and G2/M accumulation. Expression of relevant MYB target genes including BCL2 and CCNB1 was suppressed by CDK9 inhibition, and this too was reversed by ectopic MYB expression. Nevertheless, inhibition of BCL2 alone either by MYB knockdown or by ABT-199 treatment was insufficient for significant induction of apoptosis. Further studies implied that suppression of MCL-1, a well-documented target of CDK9 inhibition, was additionally required for apoptosis induction, while maximal levels of apoptosis induced by CDK9i are likely to also involve inhibition of BCL2L1 expression. Taken together these data suggest that MYB regulation of BCL2 underlies the heightened sensitivity of ER(+ve) compared to ER(-ve) breast cancer cells to CDK9 inhibition, and that these compounds represent a potential therapeutic for ER(+ve) breast cancers and possibly other MYB-dependent cancers. PMID- 26812889 TI - Magneto-transport behaviour of Bi2Se3-xTex : role of disorder. AB - Magneto-resistance and Hall resistance measurements have been carried out in fast cooled single crystals of Bi2Se3-xTex (x = 0 to 2) in 4-300 K temperature range, under magnetic fields up to 15 T. The variation of resistivity with temperature that points to a metallic behaviour in Bi2Se3, shows an up-turn at low temperatures in the Te doped samples. Magneto-resistance measurements in Bi2Se3 show clear signatures of Shubnikov-de Hass (SdH) oscillations that gets suppressed in the Te doped samples. In the Bi2SeTe2 sample, the magneto resistance shows a cusp like positive magneto-resistance at low magnetic fields and low temperatures, a feature associated with weak anti-localisation (WAL), that crosses over to negative magneto-resistance at higher fields. The qualitatively different magneto-transport behaviour seen in Bi2SeTe2 as compared to Bi2Se3 is rationalised in terms of the disorder, through an estimate of the carrier density, carrier mobility and an analysis in terms of the Ioffe-Regel criterion with support from Hall Effect measurements. We demonstrate that by introducing Te, in the strongly disordered samples a smooth crossover of SdH and WAL can be seen in the Bi2Se3-xTex series, both of which provide signatures for the presence of topological surface states. PMID- 26812888 TI - Study by EXAFS of the local structure around Si on silicene deposited on Ag(1 1 0) and Ag(1 1 1) surfaces. AB - The local structure around the silicon atoms of silicene deposited onto Ag(1 1 0) and Ag(1 1 1) has been determined by extended x-ray absorption fine structure spectroscopy at the silicon K-edge. This study shows that silicon atoms are not in a flat honeycomb network locally buckled, but that this structure mimics the double Si(1 1 1)-plane of crystalline silicon with almost the same first and second interatomic distances (2.35 and 3.83 A) on a regularly buckled geometry. Moreover the results evidence silver atoms at a well-defined distance from the silicon ones, a signature for an interaction between the silicene sheet and silver atoms released from the substrate. PMID- 26812886 TI - Tumor resistance to vascular disrupting agents: mechanisms, imaging, and solutions. AB - The emergence of vascular disrupting agents (VDAs) is a significant advance in the treatment of solid tumors. VDAs induce rapid and selective shutdown of tumor blood flow resulting in massive necrosis. However, a viable marginal tumor rim always remains after VDA treatment and is a major cause of recurrence. In this review, we discuss the mechanisms involved in the resistance of solid tumors to VDAs. Hypoxia, tumor-associated macrophages, and bone marrow-derived circulating endothelial progenitor cells all may contribute to resistance. Resistance can be monitored using magnetic resonance imaging markers. The various solutions proposed to manage tumor resistance to VDAs emphasize combining these agents with other approaches including antiangiogenic agents, chemotherapy, radiotherapy, radioimmunotherapy, and sequential dual-targeting internal radiotherapy. PMID- 26812887 TI - Splicing factor mutations predict poor prognosis in patients with de novo acute myeloid leukemia. AB - Mutations in splicing factor (SF) genes are frequently detected in myelodysplastic syndrome, but the prognostic relevance of these genes mutations in acute myeloid leukemia (AML) remains unclear. In this study, we investigated mutations of three SF genes, SF3B1, U2AF1 and SRSF2, by Sanger sequencing in 500 patients with de novo AML and analysed their clinical relevance. SF mutations were identified in 10.8% of total cohort and 13.2% of those with intermediate risk cytogenetics. SF mutations were closely associated with RUNX1, ASXL1, IDH2 and TET2 mutations. SF-mutated AML patients had a significantly lower complete remission rate and shorter disease-free survival (DFS) and overall survival (OS) than those without the mutation. Multivariate analysis demonstrated that SFmutation was an independent poor prognostic factor for DFS and OS. A scoring system incorporating SF mutation and ten other prognostic factors was proved very useful to risk-stratify AML patients. Sequential study of paired samples showed that SF mutations were stable during AML evolution. In conclusion, SF mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression. These mutations may be potential targets for novel treatment and biomarkers for disease monitoring in AML. PMID- 26812890 TI - Health Law as Social Justice. AB - Health law is in the midst of a dramatic transformation. From a relatively narrow discipline focused on regulating relationships among individual patients, health care providers, and third-party payers, it is expanding into a far broader field with a burgeoning commitment to access to health care and assurance of healthy living conditions as matters of social justice. Through a series of incremental reform efforts stretching back decades before the Affordable Care Act and encompassing public health law as well as the law of health care financing and delivery, reducing health disparities has become a central focus of American health law and policy. This Article labels, describes, and furthers a nascent "health justice" movement by examining what it means to view health law as an instrument of social justice. Drawing on the experiences of the reproductive justice, environmental justice, and food justice movements, and on the writings of political philosophers and ethicists on health justice, I propose that health justice offers an alternative to the market competition and patient rights paradigms that currently dominate health law scholarship, advocacy, and reform. I then examine the role of law in reducing health disparities through the health justice lens. I argue that the nascent health justice framework suggests three commitments for the use of law to reduce health disparities. First, to a broader inquiry that views access to health care as one among many social determinants of health deserving of public attention and resources. Second, to probing inquiry into the effects of class, racial, and other forms of social and cultural bias on the design and implementation of measures to reduce health disparities. And third, to collective action grounded in community engagement and participatory parity. In exploring these commitments, I highlight tensions within the social justice framework and between the social justice framework and the nascent health justice movement. These tensions illustrate, rather than undermine, the power of viewing health law as social justice. They raise important questions that should prompt more fruitful and rigorous thinking within health law activism and scholarship and with regard to the relationships between law and social justice more broadly. PMID- 26812891 TI - Medical Examination of Aliens--Revisions to Medical Screening Process. Final rule. AB - The Centers for Disease Control and Prevention (CDC), within the Department of Health and Human Services (HHS), is issuing this final rule (FR) to amend its regulations governing medical examinations that aliens must undergo before they may be admitted to the United States. Based on public comment received, HHS/CDC did not make changes from the NPRM published on June 23, 2015. Accordingly, this FR will: Revise the definition of communicable disease of public health significance by removing chancroid, granuloma inguinale, and lymphogranuloma venereum as inadmissible health-related conditions for aliens seeking admission to the United States; update the notification of the health-related grounds of inadmissibility to include proof of vaccinations to align with existing requirements established by the Immigration and Nationality Act (INA); revise the definitions and evaluation criteria for mental disorders, drug abuse and drug addiction; clarify and revise the evaluation requirements for tuberculosis; clarify and revise the process for the HHS/CDC-appointed medical review board that convenes to reexamine the determination of a Class A medical condition based on an appeal; and update the titles and designations of federal agencies within the text of the regulation. PMID- 26812892 TI - Reply from the Author. PMID- 26812893 TI - Stroke and interventional neurology. PMID- 26812894 TI - The Value of Medicaid. PMID- 26812896 TI - [prof. MUDr. Ales Rejther, CSc. (30.6.1938-16.10.2016)]. PMID- 26812895 TI - Medical Spending of the Elderly. PMID- 26812897 TI - [In Process Citation]. PMID- 26812898 TI - [In Process Citation]. PMID- 26812899 TI - Health and social justice: the role of today's physician. PMID- 26812900 TI - Actinopolyspora salinaria sp. nov., a halophilic actinomycete isolated from solar saltern soil. AB - The taxonomic position of the halophilic actinobacterial strain, HS05-03T, isolated from solar saltern soil, was determined using a polyphasic approach. Phylogenetic analysis based on the 16S rRNA gene sequence of the strain showed that it formed a distinct evolutionary lineage in the genus Actinopolyspora. The organism was most closely related to the type strains of the species Actinopolyspora xinjiangensis (98.0% similarity), Actinopolyspora righensis (97.9% similarity), Actinopolyspora lacussalsi (97.9% similarity) and Actinopolyspora erythraea (97.8% similarity). The whole-organism hydrolysates contained meso-diaminopimelic acid, arabinose, galactose and ribose. The predominant menaquinones were found to be MK-9(H4) and MK-10(H4). The acyl type of the peptidoglycan was N-acetyl. The diagnostic phospholipid detected was phosphatidylcholine. The predominant cellular fatty acids were iso-C16 : 0, anteiso-C17:0 and iso-C15:0. The G+C content of the genomic DNA was 69.9 mol%. DNA-DNA hybridization values between strain HS05-03T and the type strains of the most closely related species were below the 70 % threshold. On the basis of the phenotypic and genotypic data, it is proposed that strain HS05-03T represents a novel species of the genus Actinopolyspora, with the name Actinopolyspora salinaria sp. nov. The type strain is HS05-03T (=BCC 51286T=NBRC 109078T). PMID- 26812901 TI - Pre-treatment neutrophil to lymphocyte ratio predicts the chemoradiotherapy outcome and survival in patients with oral squamous cell carcinoma: a retrospective study. AB - BACKGROUND: The Neutrophil to lymphocyte ratio (NLR) has prognostic value in patients with a variety of cancers. However, its prognostic significance in oral squamous cell carcinoma (OSCC) patients has not been fully explored. The purpose of this study was to determine the clinical significance of NLR in patients with OSCC. METHODS: OSCC patients who underwent surgery following 5-fluorouracil (5 FU)-based chemoradiotherapy were enrolled in this study. The associations between the NLR status and various clinicopathological features were examined, and the effects of the NLR on the prognosis were evaluated. Analysis of circulating interleukin-6 (IL-6) was carried out and correlation with NLR and C-reactive protein concentration (CRP) was examined. RESULTS: An elevated NLR was significantly correlated with advanced T-stage and poor response to chemoradiotherapy. Moreover, a Cox regression analysis based on the disease-free survival (DFS) revealed the NLR status (hazard ratio, 2.013; P = 0.041) and pathological response to chemoradiotherapy (hazard ratio, 0.226; P = 0.001) to be significant prognostic factors in OSCC patients. Furthermore, circulating IL-6 was found to correlate with NLR and CRP. CONCLUSION: The NLR is a potential biomarker for predicting the clinical response to 5-FU-based chemoradiotherapy and the survival in OSCC patients, and the systemic inflammatory response may be potential target for improving patient's prognosis. PMID- 26812903 TI - European cancer mortality predictions for the year 2016 with focus on leukaemias. AB - BACKGROUND: Current cancer mortality statistics are important for public health decision-making and resource allocation. Age-standardized rates and numbers of deaths are predicted for 2016 in the European Union (EU). PATIENTS AND METHODS: Population and death certification data for stomach, colorectum, pancreas, lung, breast, uterus, prostate, leukaemias and total cancers were obtained from the World Health Organization database and Eurostat. Figures were derived for the EU, France, Germany, Italy, Poland, Spain and the UK. Projected numbers of deaths by age group were obtained for 2016 by linear regression on estimated numbers of deaths over the most recent time period identified by a joinpoint regression model. RESULTS: Projected total cancer mortality trends for 2016 in the EU are favourable in both sexes with rates of 133.5/100 000 men and 85.2/100 000 women (8% and 3% falls since 2011) corresponding to 753 600 and 605 900 deaths in men and women for a total number of 1 359 500 projected cancer deaths (+3% compared with 2011, due to population ageing). In men, lung, colorectal and prostate cancer have fallen 11%, 5% and 8%, respectively, since 2011. Breast and colorectal cancer trends in women are favourable (8% and 7% falls, respectively), but lung and pancreatic cancer rates have risen 5% and 4% since 2011 reaching rates of 14.4 and 5.6/100 000 women. Leukaemias show favourable projected mortality for both sexes and all age groups, with stronger falls in the younger age groups. All ages rates are 4.0/100 000 men and 2.5/100 000 women, with falls of 14% and 12% respectively. CONCLUSION: The 2016 predictions for EU cancer mortality confirm the favourable trends in rates particularly for men. Lung cancer is likely to be the leading site for female cancer rates. Continuing falls in mortality, larger in children and young adults, are predicted in leukaemias, essentially due to advancements in management and therapy, and their subsequent adoption across Europe. PMID- 26812904 TI - Cardiovascular-Active Venom Toxins: An Overview. AB - Animal venoms are a mixture of bioactive compounds produced as weapons and used primarily to immobilize and kill preys. As a result of the high potency and specificity for various physiological targets, many toxins from animal venoms have emerged as possible drugs for the medication of diverse disorders, including cardiovascular diseases. Captopril, which inhibits the angiotensin-converting enzyme (ACE), was the first successful venom-based drug and a notable example of rational drug design. Since captopril was developed, many studies have discovered novel bradykinin-potentiating peptides (BPPs) with actions on the cardiovascular system. Natriuretic peptides (NPs) have also been found in animal venoms and used as template to design new drugs with applications in cardiovascular diseases. Among the anti-arrhythmic peptides, GsMTx-4 was discovered to be a toxin that selectively inhibits the stretch-activated cation channels (SACs), which are involved in atrial fibrillation. The present review describes the main components isolated from animal venoms that act on the cardiovascular system and presents a brief summary of venomous animals and their venom apparatuses. PMID- 26812902 TI - Working memory and processing speed training in schizophrenia: study protocol for a randomized controlled trial. AB - BACKGROUND: In most domains of cognition, individuals with schizophrenia are generally found to be one standard deviation below the mean of the controls. As a result, examining the impact of cognitive remediation in individuals with schizophrenia has been a burgeoning area of research. However, the state of the literature remains unclear as to which domains of cognition should be targeted to produce the most widespread and durable benefits for individuals with schizophrenia. One suggestion is that targeting lower-level cognitive processes that are important for higher-level and more complex aspects of cognition may produce the most widespread benefits in cognition and everyday functioning. Relatively few studies have examined the effects of working memory or processing speed training in schizophrenia, as most studies examine broad-based remediation programs. Thus, a need exists for targeted working memory and processing speed training studies to better understand the mechanisms of cognitive enhancement in patients. This study aims to 1) investigate near-transfer gains (that is, the transfer of learning to related contexts) associated with working memory and processing speed training in schizophrenia patients; 2) investigate far-transfer gains (that is, the transfer of learning to new contexts) associated with working memory and processing speed training (that is, gains in other neurocognitive domains and social cognition); and 3) investigate real-world gains associated with training (that is, gains in daily functioning). METHODS/DESIGN: A double blind randomized controlled trial with a three parallel group design will be conducted. A random sample of 81 patients with schizophrenia or schizoaffective disorder will be recruited through outpatient clinics at Foothills Hospital and community support programs in Calgary, Alberta. Participants will be randomly assigned using a computer-generated program in a 1:1:1 ratio to a working memory training group, a processing speed-training group, or a no-training control group. Training will be completed at home for 30 minutes per day, 5 days per week, for a total of 10 weeks. Neurocognitive, social cognitive, and daily functioning measures will be administered both pre- and post-training to detect training-related gains. The primary outcome measures will include working memory and processing speed (near-transfer measures), as well as fluid intelligence (far transfer measure). TRIAL REGISTRATION: Current controlled trials NCT02478827 (ClinicalTrials.gov, registered on 15 June 2015). PMID- 26812905 TI - Cost-effectiveness of remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction. AB - AIMS: Remote ischaemic conditioning seems to improve long-term clinical outcomes in patients undergoing primary percutaneous coronary intervention. Remote ischaemic conditioning can be applied with cycles of alternating inflation and deflation of a blood-pressure cuff. We evaluated the cost-effectiveness of remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction from the perspective of the Danish healthcare system. METHODS AND RESULTS: Between February 2007 and November 2008, 251 patients with ST-elevation myocardial infarction were randomly assigned to remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention (n=126) or to primary percutaneous coronary intervention alone (n=125). During a 4-year follow-up period, we used data from Danish medical registries and medical records to estimate within-trial cardiovascular medical care costs and major adverse cardiac and cerebrovascular event-free survival. After 4 years of follow-up, mean cumulative cardiovascular medical care costs were ?2763 (95% confidence interval 207-5318, P=0.034) lower in the remote ischaemic conditioning group than in the control group (?12,065 vs. ?14,828), while mean major adverse cardiac and cerebrovascular event-free survival time was 0.30 years (95% confidence interval 0.03-0.57, P=0.032) higher in the remote ischaemic conditioning group than in the control group (3.51 vs. 3.21 years). In the cost-effectiveness plane, remote ischaemic conditioning therapy was economically dominant (less costly and more effective) in 97.26% of 10,000 bootstrap replications. CONCLUSION: Remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention appears to be a cost effective treatment strategy in patients with ST-elevation myocardial infarction. PMID- 26812907 TI - A geometric method for computing ocular kinematics and classifying gaze events using monocular remote eye tracking in a robotic environment. AB - BACKGROUND: Robotic and virtual-reality systems offer tremendous potential for improving assessment and rehabilitation of neurological disorders affecting the upper extremity. A key feature of these systems is that visual stimuli are often presented within the same workspace as the hands (i.e., peripersonal space). Integrating video-based remote eye tracking with robotic and virtual-reality systems can provide an additional tool for investigating how cognitive processes influence visuomotor learning and rehabilitation of the upper extremity. However, remote eye tracking systems typically compute ocular kinematics by assuming eye movements are made in a plane with constant depth (e.g. frontal plane). When visual stimuli are presented at variable depths (e.g. transverse plane), eye movements have a vergence component that may influence reliable detection of gaze events (fixations, smooth pursuits and saccades). To our knowledge, there are no available methods to classify gaze events in the transverse plane for monocular remote eye tracking systems. Here we present a geometrical method to compute ocular kinematics from a monocular remote eye tracking system when visual stimuli are presented in the transverse plane. We then use the obtained kinematics to compute velocity-based thresholds that allow us to accurately identify onsets and offsets of fixations, saccades and smooth pursuits. Finally, we validate our algorithm by comparing the gaze events computed by the algorithm with those obtained from the eye-tracking software and manual digitization. RESULTS: Within the transverse plane, our algorithm reliably differentiates saccades from fixations (static visual stimuli) and smooth pursuits from saccades and fixations when visual stimuli are dynamic. CONCLUSIONS: The proposed methods provide advancements for examining eye movements in robotic and virtual-reality systems. Our methods can also be used with other video-based or tablet-based systems in which eye movements are performed in a peripersonal plane with variable depth. PMID- 26812906 TI - Significant treatment effect of adjunct music therapy to standard treatment on the positive, negative, and mood symptoms of schizophrenic patients: a meta analysis. AB - BACKGROUND: Music therapy (MT) has been used as adjunct therapy for schizophrenia for decades. However, its role is still inconclusive. A recent meta-analysis demonstrated that MT for schizophrenic patients only significantly benefits negative symptoms and mood symptoms rather than positive symptoms. In addition, the association between specific characteristics of MT and the treatment effect remains unclear. The aim of this study was to update the published data and to explore the role of music therapy in adjunct treatment in schizophrenia with a thorough meta-analysis. METHODS: We compared the treatment effect in schizophrenic patients with standard treatment who did and did not receive adjunct MT through a meta-analysis, and investigated the clinical characteristics of MT through meta-regression. RESULTS: The main finding was that the treatment effect was significantly better in the patients who received adjunct MT than in those who did not, in negative symptoms, mood symptoms, and also positive symptoms (all p < 0.05). This significance did not change after dividing the patients into subgroups of different total duration of MT, amounts of sessions, or frequency of MT. Besides, the treatment effect on the general symptoms was significantly positively associated with the whole duration of illness, indicating that MT would be beneficial for schizophrenic patients with a chronic course. CONCLUSIONS: Our meta-analysis highlights a significantly better treatment effect in schizophrenic patients who received MT than in those who did not, especially in those with a chronic course, regardless of the duration, frequency, or amounts of sessions of MT. These findings provide evidence that clinicians should apply MT for schizophrenic patients to alleviate disease severity. PMID- 26812908 TI - A longitudinal study of anxiety and cognitive decline in dementia with Lewy bodies and Alzheimer's disease. AB - BACKGROUND: Anxiety in dementia is common but not well studied. We studied the associations of anxiety longitudinally in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). METHODS: In total, 194 patients with a first-time diagnosis of dementia were included (n = 122 patients with AD, n = 72 patients with DLB). Caregivers rated the patients' anxiety using the Neuropsychiatric Inventory, and self-reported anxiety was assessed with the anxiety and tension items on the Montgomery-Asberg Depression Rating Scale. The Mini Mental State Examination was used to assess cognitive outcome, and the Clinical Dementia Rating (CDR)-Global and CDR boxes were used for dementia severity. Linear mixed effects models were used for longitudinal analysis. RESULTS: Neither in the total sample nor in AD or DLB was caregiver-rated anxiety significantly associated with cognitive decline or dementia severity over a 4-year period. However, in patients with DLB, self-reported anxiety was associated with a slower cognitive decline than in patients with AD. No support was found for patients with DLB with clinical anxiety having a faster decline than patients with DLB without clinical anxiety. Over the course of 4 years, the level of anxiety declined in DLB and increased in AD. CONCLUSIONS: Anxiety does not seem to be an important factor for the rate of cognitive decline or dementia severity over time in patients with a first-time diagnosis of dementia. Further research into anxiety in dementia is needed. PMID- 26812909 TI - Comparison of Long-Term Outcomes Between Emergency Surgery and Bridge to Surgery for Malignant Obstruction in Right-Sided Colon Cancer: A Multicenter Retrospective Study. AB - BACKGROUND: Malignant obstruction in right-sided colon (MORC) has traditionally been treated by emergency resection with primary anastomosis. The aim of this study was to evaluate short-term postoperative and long-term oncologic outcomes according to the surgical approach adopted for MORC. METHODS: A total of 1785 patients who underwent curative surgery for stage II or III colon cancer in seven hospitals were reviewed retrospectively. Seventy-four of 1785 patients had MORC. We compared the postoperative outcome and long-term oncologic outcome between the emergency surgery (ES) group (49 patients) and the bridge to surgery (BS) group (25 patients) for 74 patients with MORC. RESULTS: There were no differences in the length of the distal and proximal resection margin (p = 0.820 and p = 0.620) or the number of metastatic lymph nodes (p = 0.221). There were no differences in flatus passage (p = 0.242), start of diet (p = 0.336), hospital stay (p = 0.444), or postoperative morbidity (p = 0.762). The 5-year overall survival rates were 73.2 % in the ES group and 90.7 % in the BS group (p = 0.172). Moreover, the 5 year disease-free survival rates were 71.9 % in the ES group and 76.2 % in the BS group (p = 0.929). CONCLUSIONS: On the basis of the above results, the postoperative course of the ES group was similar to that of the BS group. In addition, the long-term oncologic outcome of the BS group was similar or slightly better than that of the ES group. BS after colonic stent may be an alternative option for MORC. PMID- 26812910 TI - The Dual Inhibition of Met and EGFR by ME22S, a Novel Met/EGFR Bispecific Monoclonal Antibody, Suppresses the Proliferation and Invasion of Laryngeal Cancer. AB - PURPOSE: It has been reported that the abnormal activation of receptor tyrosine kinases is associated with the development of many human carcinomas and the high activation of EGFR and Met mediates the tumorigenicity of laryngeal carcinoma. In this study, we have done the therapeutic efficacy of ME22S (a novel EGFR/Met bispecific antibody) in laryngeal carcinoma in vitro and in vivo was thoroughly evaluated. METHODS: The effects of ME22S on cell viability was assessed through MTT assays, and then Western blotting and immunocytochemistry were used to determine the expression of EGFR and Met. Also, wound healing and invasion assays were performed to observe the inhibitory effects of ME22S. RESULTS: We found the ability of ME22S reducing the expression of both EGFR and Met and significantly inhibiting the cell migration, invasion, and proliferation of SNU899 and HN3 in vitro. Also, the notably reduced levels of p-Met, p-ERK, and p-AKT were found when the cells were treated with only ME22S alone or with HGF together. Meanwhile, ME22S, interestingly enough, caused caspase-3-dependent apoptotic cell death when HN3 cells were treated with ME22S for 72 h, decreased the HGF-induced Slug expression, and also inhibited the tumor growth of HN3 cells in a xenograft model in vivo. CONCLUSIONS: Taken together, our findings suggest that the dual inhibition of EGFR and Met through ME22S largely suppresses the invasion and growth of laryngeal carcinoma both in vitro and in vivo, hence, can be a practical approach as a novel therapeutic strategy for the treatment of laryngeal carcinoma. PMID- 26812911 TI - Erratum to: The ultimate radiochemical nightmare: upon radio-iodination of Botulinum neurotoxin A, the introduced iodine atom itself seems to be fatal for the bioactivity of this macromolecule. PMID- 26812912 TI - Joint use of Disparate Data for the Surveillance of Zoonoses: A Feasibility Study for a One Health Approach in Germany. AB - Zoonotic diseases concern human and animal populations and are transmitted between both humans and animals. Nevertheless, surveillance data on zoonoses are collected separately for the most part in different databases for either humans or animals. Bearing in mind the concept of One Health, it is assumed that a global view of these data might help to prevent and control zoonotic diseases. In following this approach, we wanted to determine which zoonotic data are routinely collected in Germany and whether these data could be integrated in a useful way to improve surveillance. Therefore, we conducted an inventory of the existing data collections and gathered information on possible One Health surveillance areas in Germany by approaching experts through a scoping survey, personal interviews and during a workshop. In matching the information between the status quo for existing data collections and the possible use cases for One Health surveillance, this study revealed that data integration is currently hindered by missing data, missing pathogen information or a lack of timeliness, depending on the surveillance purpose. Therefore, integrating the existing data would require substantial efforts and changes to adapt the collection procedures for routine databases. Nevertheless, during this study, we observed a need for different stakeholders from the human and animal health sectors to share information to improve the surveillance of zoonoses. Therefore, our findings suggest that before the data sets from different databases are integrated for joint analyses, the surveillance could be improved by the sharing of information and knowledge through a collaboration of stakeholders from different sectors and institutions. PMID- 26812913 TI - Risk of violence in drug rehabilitation centers: perceptions of people who inject drugs in Tijuana, Mexico. AB - BACKGROUND: In 2009, Mexico reformed its health law to partially decriminalize drug possession considered for personal use and to increase mandatory referrals to certified drug rehabilitation centers in lieu of incarceration. Concurrently, news media reported violent attacks perpetrated by drug cartels against Mexican drug rehabilitation centers and instances of human rights violations by staff against people who inject drugs (PWID) in treatment. In many cases, these violent situations took place at "Peer Support" (Ayuda Mutua) drug rehabilitation centers that house a large number of drug-dependent PWID. In an effort to understand barriers to treatment uptake, we examined prevalence and correlates of perceived risk of violence at drug rehabilitation centers among PWID in Tijuana, Mexico. METHODS: Secondary analysis of baseline data collected between March 2011 and May 2013 of PWID recruited into a prospective cohort study in Tijuana. Interviewer administered surveys measured perceived risk of violence at drug rehabilitation centers by asking participants to indicate their level of agreement with the statement "going to rehabilitation puts me at risk of violence". Logistic regression was used to examine factors associated with perceived risk of violence. RESULTS: Of 733 PWID, 34.5 % perceived risk of violence at drug rehabilitation centers. In multivariate analysis, reporting ever having used crystal methamphetamine and cocaine (separately), having a great or urgent need to get help for drug use, and ever receiving professional help for drug/alcohol use were negatively associated with perceived risk of violence at drug rehabilitation centers, while having been told by law enforcement that drug rehabilitation attendance is mandatory was positively associated with perceived risk of violence. All associations were significant at a 0.05 alpha level. CONCLUSION: The perception of violence at drug rehabilitation centers among PWID does not represent the lived experience of those PWID who attended professionalized services, reported a great or urgent need to get help for their drug use and had a history of using crystal and cocaine. Professionalizing service delivery and engaging law enforcement in their new role of decriminalization and service referral for PWID could address the perceptions of violence at drug rehabilitation centers. Similarly, health authorities should expand periodic inspections at drug rehabilitation centers to guarantee quality service provision and minimize PWIDs' concerns about violence. PMID- 26812915 TI - Nitric Oxide and Major Depressive Disorder: Pathophysiology and Treatment Implications. AB - Major depressive disorder (MDD) is a multi-factorial and heterogeneous disease. Robust evidence suggests that inflammation is involved in the pathogenesis of MDD for a subpopulation of individuals. However, it remains unclear what traits and/or states precede the onset of inflammation in this subpopulation of individuals with MDD. Several recent studies have implicated nitric oxide (NO) as a critical regulator of neuroinflammation, thus suggesting a possible role in the pathophysiology of MDD. The aim of this review is to evaluate the evidentiary base supporting the hypothesis that the increased hazard for developing MDD in certain subpopulations may be mediated, in part, by inflammogenic trait and/or state variations in NO signaling pathways. We conducted a non-systematic literature search for English language studies via PubMed and Google Scholar, from 1985 to October 2014. Replicated evidence suggests that NO has contrasting effects in the central nervous system (CNS). Low concentrations of NO are neuroprotective and mediate physiological signaling whereas higher concentrations mediate neuroinflammatory actions and are neurotoxic. Certain polymorphisms in the neuronal nitric oxide synthase gene (NOS1) are associated MDD. Furthermore, state variations (e.g. decreased levels of essential co-factor, 5,6,7,8 tetrahydrobiopterin [BH4], enhanced microglial cell activity) in the NO signaling pathway are associated with an increased risk of developing MDD. Increased concentrations of NO enhance the production of reactive nitrogen species (RNS) and reactive oxygen species (ROS), which are associated with an increase in pro inflammatory cytokines. Taken together, evidences suggest that abnormalities in NO signaling may constitute a trait-marker related to MDD pathophysiology, which could be explored for novel therapeutic targets. PMID- 26812916 TI - The Adverse Effects of Smoking on Health Outcomes in Bipolar Disorder: A Review and Synthesis of Biological Mechanisms. AB - Several biological systems are implicated in the neuroprogression of bipolar disorder including but not limited to cytokine levels, oxidative stress markers, monoamine levels, tryptophan catabolite and glutamate-mediated excitotoxicity, microglial activation as well as structural and functional changes. The high rate of smoking behaviour in individuals with bipolar disorder provides the impetus for exploring shared and discrete pathogenetic mechanisms. In addition to contributing to increased mortality, smoking activates several neurobiological effector systems implicated in the progression of bipolar disorder. Here, a narrative review provides evidence and putative mechanisms of comorbid effects of BD, cigarette use, and nicotine dependence, and discusses the clinical implications of these interactions. PMID- 26812914 TI - Disparity in reimbursement for tuberculosis care among different health insurance schemes: evidence from three counties in central China. AB - BACKGROUND: Health inequity is an important issue all around the world. The Chinese basic medical security system comprises three major insurance schemes, namely the Urban Employee Basic Medical Insurance (UEBMI), the Urban Resident Basic Medical Insurance (URBMI), and the New Cooperative Medical Scheme (NCMS). Little research has been conducted to look into the disparity in payments among the health insurance schemes in China. In this study, we aimed to evaluate the disparity in reimbursements for tuberculosis (TB) care among the abovementioned health insurance schemes. METHODS: This study uses a World Health Organization (WHO) framework to analyze the disparities and equity relating to the three dimensions of health insurance: population coverage, the range of services covered, and the extent to which costs are covered. Each of the health insurance scheme's policies were categorized and analyzed. An analysis of the claims database of all hospitalizations reimbursed from 2010 to 2012 in three counties of Yichang city (YC), which included 1506 discharges, was conducted to identify the differences in reimbursement rates and out-of-pocket (OOP) expenses among the health insurance schemes. RESULTS: Tuberculosis patients had various inpatient expenses depending on which scheme they were covered by (TB patients covered by the NCMS have less inpatient expenses than those who were covered by the URBMI, who have less inpatient expenses than those covered by the UEBMI). We found a significant horizontal inequity of healthcare utilization among the lower socioeconomic groups. In terms of financial inequity, TB patients who earned less paid more. The NCMS provides modest financial protection, based on income. Overall, TB patients from lower socioeconomic groups were the most vulnerable. CONCLUSION: There are large disparities in reimbursement for TB care among the three health insurance schemes and this, in turn, hampers TB control. Reducing the gap in health outcomes between the three health insurance schemes in China should be a focus of TB care and control. Achieving equity through integrated policies that avoid discrimination is likely to be effective. PMID- 26812917 TI - The Comorbidity of Bipolar Disorder and Migraine: The Role of Inflammation and Oxidative and Nitrosative Stress. AB - Comorbid migraine in the course of bipolar disorder has been reported as highly prevalent and associated with increased morbidity. Patients with bipolar disorder and comorbid migraine tend to present with higher rates of rapid cycling, increased number of depressive episodes, more severe depression, and increased suicidality when compared to subjects with bipolar disorder alone. Both conditions display similar clinical features, such as relapsing-recovering presentation, and vulnerability to psychological and physical stress. Clinical implications of this association have been well established, however the biological underpinnings involved in both conditions remain poorly understood. Inflammation and oxidative and nitrosative stress seem to play a role as mediators in the cross-sensitization between bipolar disorder and migraine. Therefore, the present study aims to review the role of inflammation, oxidative and nitrosative stress as underlying mechanisms in the natural history of bipolar disorder comorbid with migraine. PMID- 26812918 TI - Depression and Disturbed Bone Metabolism: A Narrative Review of the Epidemiological Findings and Postulated Mechanisms. AB - Major depressive disorder (MDD) is a pervasive chronic condition that contributes substantially to the global burden of disease and disability. Adding to the complexity of this disorder are numerous associated medical comorbidities with a bidirectional impact on morbidity and mortality. In recent years, osteoporosis has been increasingly identified as a significant comorbidity of MDD. This narrative review examines the literature to summarize key epidemiological studies and discuss postulated mechanisms of interaction. Epidemiological studies have repeatedly shown an increased co-prevalence of fractures and decreased bone mineral density (BMD) in MDD. The pathophysiological mechanism underlying this interaction is undoubtedly complex and multifactorial, and proposed pathways have varying levels of evidence from preclinical and clinical models. Conceptually, the mechanisms by which depression might influence bone metabolism can be categorized into biological, behavioral, iatrogenic, and comorbidity-related factors. Biological factors include the inflammatory-mood pathway, hypothalamic pituitary-adrenal (HPA) axis dysregulation, metabolic dysfunction, and serotonin's direct and indirect effects on bone cells. Behavioral factors incorporate lifestyle choices typical in depressed patients, such as increased tobacco use or limited exercise. The prominent iatrogenic factor is the independent effects of anti-depressants on bone metabolism. Psychiatric and medical comorbidities common to both osteoporosis and MDD are also important to consider. Physical activity promotion, vitamin D supplementation, and routine BMD screening of MDD patients are simple interventions that might lead to improved outcomes for both conditions. An improved understanding of the underlying mechanisms may yield insights into novel prevention and treatment strategies to target osteoporosis and fractures in the MDD population. PMID- 26812920 TI - Fibromyalgia and Bipolar Disorder: Emerging Epidemiological Associations and Shared Pathophysiology. AB - Fibromyalgia (FM) is a prevalent disorder defined by the presence of chronic widespread pain in association with fatigue, sleep disturbances and cognitive dysfunction. Recent studies indicate that bipolar spectrum disorders frequently co-occur in individuals with FM. Furthermore, shared pathophysiological mechanisms anticipate remarkable phenomenological similarities between FM and BD. A comprehensive search of the English literature was carried out in the Pubmed/MEDLINE database through May 10th, 2015 to identify unique references pertaining to the epidemiology and shared pathophysiology between FM and bipolar disorder (BD). Overlapping neural circuits may underpin parallel clinical manifestations of both disorders. Fibromyalgia and BD are both characterized by functional abnormalities in the hypothalamic-pituitary-adrenal axis, higher levels of inflammatory mediators, oxidative and nitrosative stress as well as mitochondrial dysfunction. An over-activation of the kynurenine pathway in both illnesses drives tryptophan away from the production of serotonin and melatonin, leading to affective symptoms, circadian rhythm disturbances and abnormalities in pain processing. In addition, both disorders are associated with impaired neuroplasticity (e.g., altered brain-derived neurotrophic factor signaling). The recognition of the symptomatic and pathophysiological overlapping between FM and bipolar spectrum disorders has relevant etiological, clinical and therapeutic implications that deserve future research consideration. PMID- 26812919 TI - Potential Biomarkers for Depression Associated with Coronary Artery Disease: A Critical Review. AB - Depression, the most common mood disorder, is a leading contributor to the global burden of disease affecting more than 120 million individuals worldwide. Various pathophysiological processes underlie depression; this complexity renders it difficult to identify clinically useful diagnostic and prognostic markers, as well as treatment options. The current state of knowledge driving the management and treatment of depression remains incomplete, which underscores the need for further insight into pathways relevant to depression. Exploring co-morbid conditions, such as coronary artery disease, may be useful to further elucidate the etiopathology of depression. The present review therefore systematically identifies and critically evaluates relevant markers of depression as assessed in a high-risk population, namely patients with coronary artery disease. Biomarkers related to hypothalamicpituitary- adrenal axis dysregulation, inflammation, endothelial dysfunction, platelet activation and aggregation, serotonin activity, sympathetic nervous system activation, thyroid function, structural and morphological brain abnormalities, genetic variation, lipid metabolism, one carbon metabolism, endocannabinoid signalling irregularities, and vitamin D deficiency are reviewed. Markers exhibiting the most consistent associations with depression include tumour necrosis factor-alpha, flow-mediated dilation, endothelin-1, endothelial progenitor cells, brain-derived neurotrophic factor, and docosahexaenoic acid. Further investigating the mechanisms underlying those markers and exploring novel pathways, such as oxidative stress, will extend the current state of knowledge and potentially lead to the identification of novel therapeutic targets. PMID- 26812921 TI - Exposure to Perinatal Infections and Bipolar Disorder: A Systematic Review. AB - Bipolar disorder (BD) is a debilitating psychiatric disorder and a growing global public health issue. Notwithstanding BD has been conceptualized as a neuroprogressive illness, there are some evidences to suggest a role for neurodevelopmental pathways in the patho-etiology of this disorder. Evidences on the associations between perinatal infections and risk for bipolar disorder have been inconsistent across studies. Here, we performed a systematic review of observational studies on the relationship between exposure to perinatal pathogens and bipolar disorder. A computerized literature search of the PubMed, Embase, and PsyINFO databases till January 31(st), 2015 was performed. Twenty-three studies ultimately met inclusion criteria. Studies investigated exposure to several pathogens namely Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Herpes simplex virus-1 (HSV-1), Herpes simplex virus-2 (HSV-2), Human herpesvirus 6 (HHV-6), Toxoplasma gondii, Influenza, and Varicella zoster virus (VZV). Overall, studies provided mixed evidences. Thus, contrary to schizophrenia, the role of perinatal infections as risk factors for BD remain inconclusive. Larger studies with a prospective design would be necessary to elucidate the role of previous exposure to infectious agents as a potential risk factor for BD. PMID- 26812923 TI - Obesity-Related Colorectal Cancer: The Role of Leptin. PMID- 26812922 TI - Skeletal muscle Heat shock protein 60 increases after endurance training and induces peroxisome proliferator-activated receptor gamma coactivator 1 alpha1 expression. AB - Heat shock protein 60 (Hsp60) is a chaperone localizing in skeletal muscle mitochondria, whose role is poorly understood. In the present study, the levels of Hsp60 in fibres of the entire posterior group of hindlimb muscles (gastrocnemius, soleus, and plantaris) were evaluated in mice after completing a 6-week endurance training program. The correlation between Hsp60 levels and the expression of four isoforms of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1alpha) were investigated only in soleus. Short-term overexpression of hsp60, achieved by in vitro plasmid transfection, was then performed to determine whether this chaperone could have a role in the activation of the expression levels of PGC1alpha isoforms. The levels of Hsp60 protein were fibre-type specific in the posterior muscles and endurance training increased its content in type I muscle fibers. Concomitantly with the increased levels of Hsp60 released in the blood stream of trained mice, mitochondrial copy number and the expression of three isoforms of PGC1alpha increased. Overexpressing hsp60 in cultured myoblasts induced only the expression of PGC1 1alpha, suggesting a correlation between Hsp60 overexpression and PGC1 1 alpha activation. PMID- 26812924 TI - Quantum random walks on congested lattices and the effect of dephasing. AB - We consider quantum random walks on congested lattices and contrast them to classical random walks. Congestion is modelled on lattices that contain static defects which reverse the walker's direction. We implement a dephasing process after each step which allows us to smoothly interpolate between classical and quantum random walks as well as study the effect of dephasing on the quantum walk. Our key results show that a quantum walker escapes a finite boundary dramatically faster than a classical walker and that this advantage remains in the presence of heavily congested lattices. PMID- 26812925 TI - AbobotulinumtoxinA for Equinus Foot Deformity in Cerebral Palsy: A Randomized Controlled Trial. AB - BACKGROUND: Although botulinum toxin is a well-established treatment of focal spasticity in cerebral palsy, most trials have been small, and few have simultaneously assessed measures of muscle tone and clinical benefit. METHODS: Global, randomized, controlled study to assess the efficacy and safety of abobotulinumtoxinA versus placebo in cerebral palsy children with dynamic equinus foot deformity. Patients were randomized (1:1:1) to abobotulinumtoxinA 10 U/kg/leg, 15 U/kg/leg, or placebo injections into the gastrocnemius-soleus complex (1 or both legs injected). In the primary hierarchical analysis, demonstration of benefit for each dose required superiority to placebo on the primary (change in Modified Ashworth Scale from baseline to week 4) and first key secondary (Physician's Global Assessment at week 4) end points. RESULTS: Two hundred and forty-one patients were randomized, and 226 completed the study; the intention to treat population included 235 patients (98%). At week 4, Modified Ashworth Scale scores significantly improved with abobotulinumtoxinA; mean (95% confidence interval) treatment differences versus placebo were -0.49 (-0.75 to 0.23; P = .0002) for 15 U/kg/leg and -0.38 (-0.64 to -0.13; P = .003) for 10 U/kg/leg. The Physician's Global Assessment treatment differences versus placebo of 0.77 (0.45 to 1.10) for 15 U/kg/leg and 0.82 (0.50 to 1.14) for 10 U/kg/leg were also significant (both Ps < .0001). The most common treatment-related adverse event was muscular weakness (10 U/Kg/leg = 2; placebo = 1). CONCLUSIONS: AbobotulinumtoxinA improves muscle tone in children with dynamic equinus resulting in an improved overall clinical impression and is well tolerated. PMID- 26812926 TI - Stakeholder Views of Clinical Trials in Low- and Middle-Income Countries: A Systematic Review. AB - CONTEXT: Clinical trials are necessary to improve the health care of children, but only one-quarter are conducted in the low- to middle-income countries (LMICs) in which 98% of the global burden of disease resides. OBJECTIVE: To describe stakeholder beliefs and experiences of conducting trials in children in LMICs. DATA SOURCES: Electronic databases were searched to August 2014. STUDY SELECTION: Qualitative studies of stakeholder perspectives on conducting clinical trials among children in LMICs. DATA EXTRACTION: Findingswere analyzed by using thematic synthesis. RESULTS: Thirty-nine studies involving 3110 participants (children [n = 290], parents or caregivers [n = 1609], community representatives [n = 621], clinical or research team members [n = 376], regulators [n = 18], or sponsors [n = 15]) across 22 countries were included. Five themes were identified: centrality of community engagement (mobilizing community, representatives' pivotal role, managing expectations, and retaining involvement); cognizance of vulnerability and poverty (therapeutic opportunity and medical mistrust); contending with power differentials (exploitation, stigmatization, and disempowerment); translating research to local context (cultural beliefs, impoverishment constraints, and ethical pluralism); and advocating fair distribution of benefits (health care, sponsor obligation, and collateral community benefits). LIMITATIONS: Studies not published in English were excluded. CONCLUSIONS: Conducting trials in children in LMICs is complex due to social disadvantage, economic scarcity, idiosyncratic cultural beliefs, and historical disempowerment, all of which contribute to inequity, mistrust, and fears of exploitation. Effective community engagement in recruiting, building research capacities, and designing trials that are pragmatic, ethical, and relevant to the health care needs of children in LMICs may help to improve the equity and health outcomes of this vulnerable population. PMID- 26812927 TI - Hereditary Angioedema Presenting as Recurrent Acute Pancreatitis. AB - Hereditary angioedema (HAE) may manifest with swelling of the face, extremities, and upper airways. Gastrointestinal symptoms are also common and may include abdominal pain, vomiting, and diarrhea. However, pancreatic involvement is rare and has been reported only in a few adults with previously diagnosed HAE. We describe a 6-year-old boy who presented with recurrent severe abdominal pain accompanied by an elevation in pancreatic enzyme levels, without subcutaneous or cutaneous angioedema. His symptoms had begun 18 months earlier, and he was hospitalized several times before the present admission with a diagnosis of acute pancreatitis. More comprehensive analysis yielded low levels of C2, C4, CH50, and C1 esterase inhibitor, establishing the diagnosis of HAE. One year after diagnosis, swelling of the extremities appeared for the first time. This is the first report of a child in whom pancreatic disease was the presenting symptom of HAE. HAE should be included in the differential diagnosis of recurrent pancreatitis in children. PMID- 26812928 TI - Recombinant growth hormone therapy in a girl with Costello syndrome: a 4-year observation. AB - BACKGROUND: Costello syndrome is a rare syndrome of multiple congenital anomalies. The typical clinical traits include dysmorphic craniofacial features, skin hyperpigmentation and excess, feeding difficulties leading to severe postnatal growth retardation, short stature, joint hypermobility, and delayed psychomotor development. Additionally, Costello syndrome may present with an increased incidence of congenital heart disease, hypertrophic cardiomyopathy, and increased risk of both benign and malignant tumors. Furthermore, cases of patients with endocrine disorders such as adrenal insufficiency and endogenous growth hormone deficiency have also been documented. CASE PRESENTATION: We present a patient with Costello syndrome who has been successfully treated with recombinant human growth hormone (rhGH) for almost 4 years. CONCLUSIONS: The possibility of growth hormone (GH) treatment can be considered in cases of documented GH deficiency in patients with Costello syndrome, but only under close oncologic and cardiologic supervision. PMID- 26812929 TI - Sixty seconds on . . . Zika virus. PMID- 26812930 TI - Injection therapy for Peyronie's disease: pearls of wisdom. PMID- 26812931 TI - Future of the PCI Readmission Metric. AB - Between 2013 and 2014, the Centers for Medicare and Medicaid Services and the National Cardiovascular Data Registry publically reported risk-adjusted 30-day readmission rates after percutaneous coronary intervention (PCI) as a pilot project. A key strength of this public reporting effort included risk adjustment with clinical rather than administrative data. Furthermore, because readmission after PCI is common, expensive, and preventable, this metric has substantial potential to improve quality and value in American cardiology care. Despite this, concerns about the metric exist. For example, few PCI readmissions are caused by procedural complications, limiting the extent to which improved procedural technique can reduce readmissions. Also, similar to other readmission measures, PCI readmission is associated with socioeconomic status and race. Accordingly, the metric may unfairly penalize hospitals that care for underserved patients. Perhaps in the context of these limitations, Centers for Medicare and Medicaid Services has not yet included PCI readmission among metrics that determine Medicare financial penalties. Nevertheless, provider organizations may still wish to focus on this metric to improve value for cardiology patients. PCI readmission is associated with low-risk chest discomfort and patient anxiety. Therefore, patient education, improved triage mechanisms, and improved care coordination offer opportunities to minimize PCI readmissions. Because PCI readmission is common and costly, reducing PCI readmission offers provider organizations a compelling target to improve the quality of care, and also performance in contracts involve shared financial risk. PMID- 26812933 TI - Dabigatran Versus Warfarin for Atrial Fibrillation in Real-World Clinical Practice: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Trial data for the benefits and risks of dabigatran versus warfarin in the treatment of nonvalvular atrial fibrillation are lacking. We sought to review real-world observational evidence for the comparative effectiveness and safety of these agents. METHODS AND RESULTS: A systematic search of multiple databases was conducted from first available date to March 10, 2015 for longitudinal, observational studies comparing dabigatran with warfarin. Two reviewers evaluated studies for eligibility and extracted hazard ratios for ischemic stroke and gastrointestinal and intracranial bleeding. hazard ratios were pooled using random-effects meta-analysis. Metaregression was performed to assess treatment-effect heterogeneity. We identified 232 unique citations. Seven retrospective cohort studies met study eligibility criteria, with 348 750 patients and a mean follow-up of 2.2 years. In pooled analyses, dabigatran-150 mg was not superior to warfarin in preventing stroke (hazard ratio, 0.92; 95% confidence interval, 0.84-1.01; P=0.066), but had a significantly lower hazard of intracranial bleeding (0.44; 0.34-0.59; P<0.001). Dabigatran-150 mg had a significantly greater hazard of gastrointestinal bleeding than warfarin (1.23; 1.01-1.50; P=0.041), which was potentiated in studies of older (elderly) versus younger populations (median/mean age, >=75 versus <75 years; beta=1.53; 95% confidence interval, 1.10-2.14; P=0.020). CONCLUSIONS: In real-world clinical practice, dabigatran is comparable with warfarin in preventing ischemic stroke among patients with nonvalvular atrial fibrillation. However, dabigatran is associated with a lower risk for intracranial bleeding relative to warfarin, but particularly among the elderly-a greater risk for gastrointestinal bleeding. Bleeding outcomes from observational studies are consistent with those from the pivotal Randomized Evaluation of Long-Term Anticoagulation Therapy trial. PMID- 26812932 TI - Paramedic Exposure to Out-of-Hospital Cardiac Arrest Resuscitation Is Associated With Patient Survival. AB - BACKGROUND: Although out-of-hospital cardiac arrest (OHCA) is a major public health problem, individual paramedics are rarely exposed to these cases. In this study, we examined whether previous paramedic exposure to OHCA resuscitation is associated with patient survival. METHODS AND RESULTS: For the period 2003 to 2012, we linked data from the Victorian Ambulance Cardiac Arrest Registry to Ambulance Victoria's employment data set. We defined exposure as the number of times a paramedic attended an OHCA where resuscitation was attempted in the 3 years preceding each case. Using a multivariable model adjusting for known predictors of survival, we measured the association between paramedic OHCA exposure and patient survival to hospital discharge. During the study period, there were 4151 paramedics employed and 48 291 OHCAs (44% with resuscitation attempted). The median exposure of all paramedics was 2 (interquartile range 1-3) OHCAs/year. Eleven percent of paramedics were not exposed to any OHCA cases. Increased paramedic exposure was associated with reduced odds of attempted resuscitation (P<0.001). In the 3 years preceding each OHCA where resuscitation was attempted, the median exposure of the treating paramedics was 11 (interquartile range 6-17) OHCAs. Compared with patients treated by paramedics with a median of <=6 exposures during the previous 3 years (7% survival), the odds of survival were higher for patients treated by paramedics with >6 to 11 (12%, adjusted odds ratio 1.26, 95% confidence interval 1.04-1.54), >11 to 17 (14%, adjusted odds ratio 1.29, 95% confidence interval 1.04-1.59), and >17 exposures (17%, adjusted odds ratio 1.50, 95% confidence interval 1.22-1.86). Paramedic years of experience were not associated with survival. CONCLUSIONS: Patient survival after OHCA significantly increases with the number of OHCAs that paramedics have previously treated. PMID- 26812934 TI - Care Transitions After Acute Myocardial Infarction for Transferred-In Versus Direct-Arrival Patients. AB - BACKGROUND: Many patients in the United States require transfer from one hospital to another for acute myocardial infarction (MI) care. How well these transferred in patients are transitioned back to their local community is unknown. METHODS AND RESULTS: We used linked Medicare claims data to examine postdischarge outcomes of 39 136 patients with acute MI aged >=65 years discharged alive from 451 US hospitals in Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines. Multivariable Cox modeling was used to compare the likelihood of outpatient clinic follow-up and risks of all-cause mortality and all-cause or cardiovascular readmission at 30 days post MI between transferred-in and direct-arrival patients. From 2007 to 2010, 14 060 of 39 136 patients (36%) required interhospital transfer for acute MI care, traveling a median of 43 miles (interquartile range, 27-68 miles; 77.6 km [interquartile range, 48.2-122.6 km]). Compared with those arriving directly, transferred-in patients with MI were slightly younger (median age, 73 versus 74; P<0.01) but less likely to have previous MI, heart failure, and previous revascularization than direct-arrival patients. Relative to direct-arrival patients, those transferred-in had a lower likelihood of outpatient follow-up within 30 days post discharge (risk-adjusted incidence, 69.9% versus 78.2%; hazard ratio [HR], 0.90; 95% confidence interval, 0.87-0.92) and higher adjusted 30-day all-cause and cardiovascular readmission risks (14.5% versus 14.0%; HRall-cause, 1.08; 95% confidence interval, 1.01-1.15 and 9.5% versus 9.1%; HRcardiovascular, 1.13; 95% confidence interval, 1.04-1.22). In contrast, risk-adjusted 30-day mortality was similar between transferred-in and direct arrivals (1.6% versus 1.6%; HR, 1.05; 95% confidence interval, 0.86-1.27). CONCLUSIONS: Transferred-in patients with acute MI are less likely to have outpatient clinic follow-up within 30 days and more likely to be readmitted within the first 30 days post discharge compared with direct-arrival patients. These results indicate room for improvement in the safe and seamless transition of care for transferred patients with MI traveling back to their home environments. PMID- 26812935 TI - Management of Cyclosporine and Nifedipine-Induced Gingival Hyperplasia. AB - Gingival enlargements modified by medications are becoming more common because of the increased use of inducing drugs, and may create speech, mastication, tooth eruption, periodontal, and aesthetic problems. We hereby present a case of a 54 year-old man with 12-month history of generalized gingival enlargement in the keratinized gingiva was referred to our clinic. The patient had a history of kidney transplant and was under medication of cyclosporine and nifedipine. After medical consultation, cyclosporine was changed to tacrolimus and nifedipine was changed to captopril. Gingivectomy was performed using a diode laser, and scaling and root planning were performed. At five months postoperative, the gingival enlargements relapsed and diode laser-assisted surgery was repeated. The patient was followed-up on second postoperatively at 18 months and no relapse was seen. Diode laser-assisted gingivectomy was found to be useful for coagulation during surgery and decreased postoperative bleeding. Recurrence risk of cyclosporine and nifedipine-induced gingival overgrowth is high, thus, there is a great need for prolonged care of patients following treatment and prosthetic restoration. PMID- 26812936 TI - School-Based Speech-Language Pathologists' Knowledge and Perceptions of Autism Spectrum Disorder and Bullying. AB - PURPOSE: The purpose of the current investigation was to examine speech-language pathologists' (SLPs') knowledge and perceptions of bullying, with an emphasis on autism spectrum disorder (ASD). METHOD: A 46-item, web-based survey was used to address the purposes of this investigation. Participants were recruited through e mail and electronic mailing lists for American Speech-Language-Hearing Association (ASHA) special interest divisions 1 (Language, Learning, and Education) and 16 (School-Based Issues). Also, an embedded link to the survey was posted on the ASHA Community website and ASHA Facebook page. RESULTS: Participants demonstrated knowledge of many aspects of bullying research; however, they demonstrated weaknesses in others. All respondents agreed that SLPs should intervene in moments of bullying, but not all indicated that they feel comfortable intervening. Few participants indicated that their school district implemented antibullying campaigns specific to children with special needs, such as ASD. CONCLUSIONS: As recognized experts in working with children with communication deficits, including individuals with ASD, SLPs have the opportunity to play a key role in antibullying efforts. Results revealed, however, that school-based SLPs may benefit from more information on bullying in order to understand the nature, context, and extent of this issue, as well as ways in which to respond to bullying when it is observed. PMID- 26812937 TI - Detection of Early Stage Apoptotic Cells Based on Label-Free Cytochrome c Assay Using Bioconjugated Metal Nanoclusters as Fluorescent Probes. AB - Cytochrome c (Cyt c) is an important biomarker in cell lysates for the early stage of apoptosis or anticancer agents. Here, two novel label-free fluorescence assays based on hemoglobin-stabilized gold nanoclusters (Hb/AuNCs) and aptamer stabilized silver nanoclusters (DNA/AgNCs) for analysis of Cyt c are presented. The heme group of the protein induces sensitive sensing platforms accompanied by the decreased fluorescence of both metal nanoclusters. The quenching processes observed found to be based on the fluorescence resonance energy transfer mechanism from Hb/AuNCs to Cyt c and photoinduced electron transfer from DNA/AgNCs to the aptamer-Cyt c complex. The linear range for Cyt c was found to be 0-10 MUM for Hb/AuNCs and from 0 to 1 MUM for DNA/AgNCs, with limits of detection of ~15 nM. On the basis of strong binding affinity of DNA aptamers for their target proteins, the DNA/AgNCs probe was successfully applied to the quantitative determination of Cyt c in cell lysates, which opens a new avenue to early diagnostics and drug screening with high sensitivity. Compared to the conventional Western blot method, the presented assays are low cost, easy to prepare the fluorescent probes, and sensitive, while overall time for the detection and quantitation of Cyt c from isolated mitochondria is only 20 min. The proposed method for Cyt c detection may also be useful for the study of those materials that cause mitochondrial dysfunction and apoptotic cell death. PMID- 26812939 TI - Re: Review article titled 'Clinical benefits and impact of early use of long acting injectable antipsychotics for schizophrenia' (Stevens GL et al. Early Interv Psychiatry 2015 Sep 25. doi: 10.1111/eip.12278). PMID- 26812938 TI - First report of human parvovirus 4 detection in Iran. AB - Parvovirus 4 (PARV4) is an emerging and intriguing virus that currently received many attentions. High prevalence of PARV4 infection in high-risk groups such as HIV infected patients highlights the potential clinical outcomes that this virus might have. Molecular techniques were used to determine both the presence and the genotype of circulating PARV4 on previously collected serum samples from 133 HIV infected patients and 120 healthy blood donors. Nested PCR was applied to assess the presence of PARV4 DNA genome in both groups. PARV4 DNA was detected in 35.3% of HIV infected patients compared to 16.6% healthy donors. To genetically characterize the PARV4 genotype in these groups, positive samples were randomly selected and subjected for sequencing and phylogenetic analysis. All PARV4 sequences were found to be genotype 1 and clustered with the reference sequences of PARV4 genotype 1. J. Med. Virol. 88:1314-1318, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26812942 TI - Orientation-Induced Effects of Water Harvesting on Humps-on-Strings of Bioinspired Fibers. AB - Smart water-collecting functions are naturally endowed on biological surfaces with unique wettable microstructures, e.g., beetle back with "alternate hydrophobic, hydrophilic micro-regions", and spider silk with wet-rebuilt "spindle-knot, joint" structures. Enlightened by the creature features, design of bio-inspired surfaces becomes the active issue in need of human beings for fresh water resource. Recently, as observed from spider web in nature, the net of spider silk is usually set in different situations and slopes in air, thus spider silks can be placed in all kinds of orientations as capturing water. Here, we show the styles and orientations of hump-on-string to control the ability of water collection as bioinspired silks are fabricated successfully. As different strings, sizes (height, length, pitch) of humps can become the controlling on volumes of extreme water drops. It is related to the different solid/liquid contact regions resulting in the as-modulated wet adhesion due to orientations of humps-on-strings. The conversion of high-low adhesion can be achieved to rely on orientations for the effect of capturing water drops. These studies offer an insight into enhancement of water collection efficiency and are helpful to design smart materials for controlled water drop capture and release via conversions of high-low adhesion. PMID- 26812943 TI - Towards new treatment options for renal cell carcinoma: development and clinical results of tivozanib, a selective VEGFR tyrosine kinase inhibitor. PMID- 26812941 TI - Donors' health state the year after peripheral haematopoietic progenitor cell collection: A prospective follow-up study in related and unrelated donors compared to first-time platelet donors. AB - Granulocyte colony-stimulating factor (G-CSF) mobilized peripheral haematopoietic progenitor cells collected by apheresis (HPC-A) are the most common source used for allogeneic hematopoietic stem cell transplantation (HSCT). Retrospective short and long-term donor follow-up studies show very low risks of serious complications and do not report compelling evidence of increased cancer occurrence. Some studies reported a prolonged period of leucopenia without an obvious association with infectious complications. However, beyond the first few weeks after the procedure a relationship between events is elusive. We therefore evaluated medical service utilization by prospectively recruited HPC-A donors and first-time platelet apheresis donors for comparison for 1 year after donation. Data were prospectively collected using questionnaires and by medical record review. A total of 215 HPC-A donors (111 unrelated donors and 104 related donors) and 96 first-time platelet donors consented to participation in the study. Follow up was available for 202 (96%): questionnaires were returned by 74% and records from nonstudy contacts were available for 94% of donors. During the 1-year follow up, 94 of the donors who returned questionnaires sought medical attention for diagnostic evaluation and/or treatment: 41% of HPC-A donors and 40% of platelet donors. Medical service utilization the first year after HPC-A donation is similar to that after first-time platelet donation. The occurrence of serious medical conditions in both related and unrelated HPC-A donors underscores the importance of participation in long-term follow-up in large cohorts. The findings in this relatively small cohort contribute to evidence on the safety of G-CSF mobilization and HPC-A. J. Clin. Apheresis 31:523-528, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26812944 TI - Vertebral Compression Fractures--the Missed Opportunities. PMID- 26812940 TI - Generating trunk neural crest from human pluripotent stem cells. AB - Neural crest cells (NCC) are stem cells that generate different lineages, including neuroendocrine, melanocytic, cartilage, and bone. The differentiation potential of NCC varies according to the level from which cells emerge along the neural tube. For example, only anterior "cranial" NCC form craniofacial bone, whereas solely posterior "trunk" NCC contribute to sympathoadrenal cells. Importantly, the isolation of human fetal NCC carries ethical and scientific challenges, as NCC induction typically occur before pregnancy is detectable. As a result, current knowledge of NCC biology derives primarily from non-human organisms. Important differences between human and non-human NCC, such as expression of HNK1 in human but not mouse NCC, suggest a need to study human NCC directly. Here, we demonstrate that current protocols to differentiate human pluripotent stem cells (PSC) to NCC are biased toward cranial NCC. Addition of retinoic acid drove trunk-related markers and HOX genes characteristic of a posterior identity. Subsequent treatment with bone morphogenetic proteins (BMPs) enhanced differentiation to sympathoadrenal cells. Our approach provides methodology for detailed studies of human NCC, and clarifies roles for retinoids and BMPs in the differentiation of human PSC to trunk NCC and to sympathoadrenal lineages. PMID- 26812946 TI - Decompensated alcohol related liver disease: acute management. PMID- 26812945 TI - Outcomes of patients admitted to intensive care units for acute manifestation of small-vessel vasculitis: a multicenter, retrospective study. AB - BACKGROUND: The outcomes of patients admitted to the intensive care unit (ICU) for acute manifestation of small-vessel vasculitis are poorly reported. The aim of the present study was to determine the mortality rate and prognostic factors of patients admitted to the ICU for acute small-vessel vasculitis. METHODS: This retrospective, multicenter study was conducted from January 2001 to December 2014 in 20 ICUs in France. Patients were identified from computerized registers of each hospital using the International Classification of Diseases, Ninth Revision (ICD-9). Inclusion criteria were (1) known or highly suspected granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis (respectively, ICD-9 codes M31.3, M30.1, and M31.7), or anti glomerular basement membrane antibody disease (ICD-9 codes N08.5X-005 or M31.0+); (2) admission to the ICU for the management of an acute manifestation of vasculitis; and (3) administration of a cyclophosphamide pulse in the ICU or within 48 h before admission to the ICU. The primary endpoint was assessment of mortality rate 90 days after admission to the ICU. RESULTS: Eighty-two patients at 20 centers were included, 94% of whom had a recent (<6 months) diagnosis of small-vessel vasculitis. Forty-four patients (54%) had granulomatosis with polyangiitis. The main reasons for admission were respiratory failure (34%) and pulmonary-renal syndrome (33%). Mechanical ventilation was required in 51% of patients, catecholamines in 31%, and renal replacement therapy in 71%. Overall mortality at 90 days was 18% and the mortality in ICU was 16 %. The main causes of death in the ICU were disease flare in 69% and infection in 31%. In univariable analysis, relevant factors associated with death in nonsurvivors compared with survivors were Simplified Acute Physiology Score II (median [interquartile range] 51 [38-82] vs. 36 [27-42], p = 0.005), age (67 years [62 74] vs. 58 years [40-68], p < 0.003), Sequential Organ Failure Assessment score on the day of cyclophosphamide administration (11 [6-12] vs. 6 [3-7], p = 0.0004), and delayed administration of cyclophosphamide (5 days [3-14] vs. 2 days [1-5], p = 0.0053). CONCLUSIONS: Patients admitted to the ICU for management of acute small-vessel vasculitis benefit from early, aggressive intensive care treatment, associated with an 18% death rate at 90 days. PMID- 26812947 TI - Right Ventricular and Right Atrial Involvement Can Predict Atrial Fibrillation in Patients with Hypertrophic Cardiomyopathy? AB - OBJECTIVES AND BACKGROUND: Atrial fibrillation (AF) is associated with clinical deterioration, stroke and disability in patients with hypertrophic cardiomyopathy (HCM). Therefore, the objective of this study was to evaluated cardiac magnetic resonance (CMR)-derived determinants for the occurrence of AF in patients with HCM. METHODS: 98 Patients with HCM and 30 healthy controls underwent CMR and were followed-up for 6 +/- 3 years. RESULTS: 19 (19.4%) patients presented with AF at initial diagnosis, 19 (19.4%) developed AF during follow-up and 60 (61.2%) remained in sinus rhythm (SR). Compared to healthy controls, patients with HCM who remained in SR presented with significantly increased left ventricular mass, an elevated left ventricular remodeling index, enlarged left atrial volumes and reduced septal mitral annular plane systolic excursion (MAPSE) compared to healthy controls. Whereas HCM patients who presented with AF at initial diagnosis and those who developed AF during follow-up additionally presented with reduced tricuspid annular plane systolic excursion (TAPSE) and right atrial (RA) dilatation. Receiver-operator curve analysis indicated good predictive performance of TAPSE, RA diameter and septal MAPSE (AUC 0.73, 0.69 and 0.71, respectively) to detect patients at risk of developing AF. CONCLUSION: Reduced MAPSE measurements and enlarged LA volumes seems to be a common feature in patients with HCM, whereas reduced TAPSE and RA dilatation only seem to be altered in patients with history of AF and those developing AF. Therefore, they could serve as easy determinable markers of AF in patients with HCM. PMID- 26812949 TI - The role of hypoxia in intestinal inflammation. AB - Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease of the intestine. IBD is a multifactorial disorder, and IBD-associated genes are critical in innate immune response, inflammatory response, autophagy, and epithelial barrier integrity. Moreover, epithelial oxygen tension plays a critical role in intestinal inflammation and resolution in IBD. The intestines have a dynamic and rapid fluctuation in cellular oxygen tension, which is dysregulated in IBD. Intestinal epithelial cells have a steep oxygen gradient where the tips of the villi are hypoxic and the oxygenation increases at the base of the villi. IBD results in heightened hypoxia throughout the mucosa. Hypoxia signals through a well-conserved family of transcription factors, where hypoxia inducible factor (HIF)-1alpha and HIF-2alpha are essential in maintaining intestinal homeostasis. In inflamed mucosa, HIF-1alpha increases barrier protective genes, elicits protective innate immune responses, and activates an antimicrobial response through the increase in beta-defensins. HIF-2alpha is essential in maintaining an epithelial-elicited inflammatory response and the regenerative and proliferative capacity of the intestine following an acute injury. HIF-1alpha activation in colitis leads to a protective response, whereas chronic activation of HIF-2alpha increases the pro-inflammatory response, intestinal injury, and cancer. In this mini-review, we detail the role of HIF 1alpha and HIF-2alpha in intestinal inflammation and injury and therapeutic implications of targeting HIF signaling in IBD. PMID- 26812948 TI - Can corneal pannus with trachomatous inflammation--follicular be used in combination as an improved specific clinical sign for current ocular Chlamydia trachomatis infection? AB - BACKGROUND: Trachoma is a blinding disease caused by conjunctival infection with Chlamydia trachomatis (Ct). Mass drug administration (MDA) for trachoma control is administered based on the population prevalence of the clinical sign of trachomatis inflammation - follicular (TF). However, the prevalence of TF is often much higher than the prevalence of Ct infection. The addition of a clinical sign specific for current ocular Ct infection to TF could save resources by preventing unnecessary additional rounds of MDA. METHODS: Study participants were aged between 1-9 years and resided on 7 islands of the Bijagos Archipelago, Guinea Bissau. Clinical grades for trachoma and corneal pannus and ocular swab samples were taken from 80 children with TF and from 81 matched controls without clinical evidence of trachoma. Ct infection testing was performed using droplet digital PCR. RESULTS: New pannus was significantly associated with Ct infection after adjustment for TF (P = 0.009, OR = 3.65 (1.4-9.8)). Amongst individuals with TF, individuals with new pannus had significantly more Ct infection than individuals with none or old pannus (75.0% vs 45.5%, Chi(2) P = 0.01). TF and new pannus together provide a highly specific (91.7%), but a poorly sensitive (51.9%) clinical diagnostic test for Ct infection. CONCLUSIONS: As we move towards trachoma elimination it may be desirable to use a combined clinical sign (new pannus in addition to TF) that is highly specific for current ocular Ct infection. This would allow national health systems to obtain a more accurate estimate of Ct population prevalence to inform further need for MDA without the expense of Ct molecular diagnostics, which are currently unaffordable in programmatic contexts. PMID- 26812950 TI - The multiple roles of sucrase-isomaltase in the intestinal physiology. AB - Osmotic diarrhea and abdominal pain in humans are oftentimes associated with carbohydrate malabsorption in the small intestine due to loss of function of microvillar disaccharidases. Disaccharidases are crucial for the digestion and the subsequent absorption of carbohydrates. This review focuses on sucrase isomaltase as the most abundant intestinal disaccharidase and the primary or induced pathological conditions that affect its physiological function. Congenital defects are primary factors which directly influence the transport and function of sucrase-isomaltase in a healthy epithelium. Based on the mutation type and the pattern of inheritance, a mutation in the sucrase-isomaltase gene may exert a variety of symptoms ranging from mild to severe. However, structure and function of wild type sucrase-isomaltase can be also affected by secondary factors which influence its structure and function either specifically via certain inhibitors and therapeutic agents or generally as a part of intestinal pathogenesis, for example in the inflammatory responses. Diagnosis of sucrase isomaltase deficiency and discriminating it from other gastrointestinal intolerances can be latent in the patients because of common symptoms observed in all of these cases.Here, we summarize the disorders that implicate the digestive function of sucrase-isomaltase as well as the diagnostic and therapeutic strategies utilized to restore normal intestinal function. PMID- 26812951 TI - Monitoring pasture variability: optical OptRx((r)) crop sensor versus Grassmaster II capacitance probe. AB - Estimation of pasture productivity is an important step for the farmer in terms of planning animal stocking, organizing animal lots, and determining supplementary feeding needs throughout the year. The main objective of this work was to evaluate technologies which have potential for monitoring aspects related to spatial and temporal variability of pasture green and dry matter yield (respectively, GM and DM, in kg/ha) and support to decision making for the farmer. Two types of sensors were evaluated: an active optical sensor ("OptRx((r))," which measures the NDVI, "Normalized Difference Vegetation Index") and a capacitance probe ("GrassMaster II" which estimates plant mass). The results showed the potential of NDVI for monitoring the evolution of spatial and temporal patterns of vegetative growth of biodiverse pasture. Higher NDVI values were registered as pasture approached its greatest vegetative vigor, with a significant fall in the measured NDVI at the end of Spring, when the pasture began to dry due to the combination of higher temperatures and lower soil moisture content. This index was also effective for identifying different plant species (grasses/legumes) and variability in pasture yield. Furthermore, it was possible to develop calibration equations between the capacitance and the NDVI (R(2) = 0.757; p < 0.01), between capacitance and GM (R(2) = 0.799; p < 0.01), between capacitance and DM (R(2) =0.630; p < 0.01), between NDVI and GM (R(2) = 0.745; p < 0.01), and between capacitance and DM (R(2) = 0.524; p < 0.01). Finally, a direct relationship was obtained between NDVI and pasture moisture content (PMC, in %) and between capacitance and PMC (respectively, R(2) = 0.615; p < 0.01 and R(2) = 0.561; p < 0.01) in Alentejo dryland farming systems. PMID- 26812952 TI - Flow monitoring with a camera: a case study on a flood event in the Tiber River. AB - Monitoring surface water velocity during flood events is a challenging task. Techniques based on deploying instruments in the flow are often unfeasible due to high velocity and abundant sediment transport. A low-cost and versatile technology that provides continuous and automatic observations is still not available. Among remote methods, large-scale particle image velocimetry (LSPIV) is an optical method that computes surface water velocity maps from videos recorded with a camera. Here, we implement and critically analyze findings obtained from a recently introduced LSPIV experimental configuration during a flood event in the Tiber River at a cross section located in the center of Rome, Italy. We discuss the potential of LSPIV observations in challenging environmental conditions by presenting results from three tests performed during the hydrograph flood peak and recession limb of the event for different illumination and weather conditions. The obtained surface velocity maps are compared to the rating curve velocity and to benchmark velocity values. Experimental findings show that optical methods should be preferred in extreme conditions. However, their practical implementation may be associated with further hurdles and uncertainties. PMID- 26812953 TI - Editorial: Mood Disorders and General Medical Comorbidities: Shared Biology and Novel Therapeutic Targets. PMID- 26812955 TI - Enhancing the carrier thermalization time in organometallic perovskites by halide mixing. AB - Hybrid metal-organic halide perovskites have recently attracted a great deal of attention because of their interesting electronic, optical and transport properties, which make them promising materials for high-performance, low-cost solar cells. Fundamental understanding of the formation mechanisms and dynamics of photoinduced charge carriers is essential for improving the performance of perovskite solar cell devices. For example, a significant amount of absorbed solar energy is lost as a result of carrier thermalization. This energy could be harnessed by extracting hot carriers before they cool down to the band edges. Although such hot carrier collection is experimentally challenging, theoretical investigations based on time-dependent methods can guide future experimental research by providing insights into the thermalization process. Here, we perform ab initio nonadiabatic molecular dynamics simulations to study non-radiative relaxation dynamics of charge carriers in hybrid halide perovskites. We find that the carrier relaxation time can be considerably increased by mixing halogen atoms in the perovskite materials. These findings show that simple approaches could be adopted to slow down the thermalization process of hot carriers in perovskite materials. PMID- 26812956 TI - Marinobacterium aestuariivivens sp. nov., isolated from a tidal flat. AB - A Gram-stain-negative, motile, aerobic, rod- or ovoid-shaped bacterium, designated DB-1T, was isolated from a tidal flat on the Yellow Sea in South Korea and subjected to a taxonomic study using a polyphasic approach. Strain DB-1T grew optimally at 30 degrees C, at pH 7.0-8.0 and in the presence of 0.5-2.0% (w/v) NaCl. The neighbour-joining phylogenetic tree based on 16S rRNA gene sequences revealed that strain DB-1T falls within the clade comprising species of the genus Marinobacterium, clustering coherently with the type strain of Marinobacterium nitratireducens and showing a sequence similarity value of 98.4 %. The novel strain exhibited 16S rRNA gene sequence similarities of 91.5-94.4 % to the type strains of other species of the genus Marinobacterium. Strain DB-1T contained Q-8 as the predominant ubiquinone and C18:1omega7c, summed feature 3 (C16:1omega7c and/or C16:1omega6c) and C16:0 as the major fatty acids. The major polar lipids detected in strain DB-1T were phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminolipid, one unidentified glycolipid, one unidentified phospholipid and two unidentified lipids. The DNA G+C content of strain DB-1T was 62.3 mol% and the mean DNA-DNA relatedness value with the type strain of M. nitratireducens was 21+/-4.6%. Differential phenotypic properties, together with phylogenetic and genetic distinctiveness, revealed that strain DB-1T is separated from recognized species of the genus Marinobacterium. On the basis of the data presented, strain DB-1T is considered to represent a novel species of the genus Marinobacterium, for which the name Marinobacterium aestuariivivens sp. nov. is proposed. The type strain is DB-1T (=KCTC 42778T=NBRC 111756T). PMID- 26812954 TI - Prediction of mortality and functional outcome from status epilepticus and independent external validation of STESS and EMSE scores. AB - BACKGROUND: Two clinical scoring systems, the status epilepticus severity score (STESS) and the epidemiology-based mortality score in status epilepticus (EMSE), are used to predict mortality in patients with status epilepticus (SE). The aim of this study was to compare the outcome-prediction function of the two scoring systems regarding in-hospital mortality using a multicenter large cohort of adult patients with SE. Moreover, we studied the potential role of these two scoring systems in predicting the functional outcome in patients with SE. METHODS: The SE cohort consisted of patients from the epilepsy centers of eight academic tertiary medical centers in South Korea. The clinical and electroencephalography data for all adult patients with SE from January 2013 to December 2014 were derived from a prospective SE database. The primary outcome variable was defined as in-hospital death. The secondary outcome variable was defined as a poor functional outcome, i.e., a score of 1-3 on the Glasgow Outcome Scale, at discharge. RESULTS: Among the 120 non-hypoxic patients with SE recruited into the study, 16 (13.3%) died in the hospital and 64 (53.3%) were discharged with a poor functional outcome. The receiver-operating characteristic (ROC) curve for prediction of in-hospital death based on the STESS had an area under the curve of 0.673 with an optimal cutoff value for discrimination (best match for both sensitivity (0.56) and specificity (0.70)) that was >= 4 points. The two combinations of elements of the EMSE system (EMSE-ALDEg and EMSE-ECLEg) predicted not only in-hospital mortality with the best match for sensitivity (more than 0.6) and specificity (more than 0.6), but also a poor functional outcome with the best match for both sensitivity (>0.7) and specificity (>0.6). STESS did not predict a poor functional outcome (area under the ROC, 0.581; P = 0.23). CONCLUSION: Although the EMSE is a clinical scoring system that focuses on individual mortality, we did not find differences between the EMSE and STESS in the prediction of in-hospital death. The EMSE was useful in predicting poor functional outcome, as it was significantly better than STESS. PMID- 26812957 TI - The development of nanostructure assisted isothermal amplification in biosensors. AB - Developing simple and inexpensive methods to ultrasensitively detect biomarkers is important for medical diagnosis, food analysis and environmental security. In recent years, isothermal amplifications with sensitivity, high speed, specificity, accuracy, and automation have been designed based on interdisciplinary approaches among chemistry, biology, and materials science. In this article, we summarize the advances in nanostructure assisted isothermal amplification in the past two decades for the detection of commercial biomarkers, or biomarkers extracted from cultured cells or patient samples. This article has been divided into three parts according to the ratio of target-to-signal probe in the detection strategy, namely, the N : N amplification ratio, the 1 : N amplification ratio, and the 1 : N(2) amplification ratio. PMID- 26812959 TI - Minimizing resource overheads for fault-tolerant preparation of encoded states of the Steane code. AB - The seven-qubit quantum error-correcting code originally proposed by Steane is one of the best known quantum codes. The Steane code has a desirable property that most basic operations can be performed easily in a fault-tolerant manner. A major obstacle to fault-tolerant quantum computation with the Steane code is fault-tolerant preparation of encoded states, which requires large computational resources. Here we propose efficient state preparation methods for zero and magic states encoded with the Steane code, where the zero state is one of the computational basis states and the magic state allows us to achieve universality in fault-tolerant quantum computation. The methods minimize resource overheads for the fault-tolerant state preparation, and therefore reduce necessary resources for quantum computation with the Steane code. Thus, the present results will open a new possibility for efficient fault-tolerant quantum computation. PMID- 26812958 TI - Dysmorphic erythrocytes are superior to hematuria for indicating non-diabetic renal disease in type 2 diabetics. AB - AIMS/INTRODUCTION: There are sparse and limited studies on erythrocyte morphology in renal biopsy identifying nephropathic patients among type 2 diabetics. The present study sought to clarify the predictive value of dysmorphic erythrocytes in type 2 diabetics with non-diabetic renal disease and influences on hematuria. MATERIALS AND METHODS: We examined 198 patients with type 2 diabetes who underwent kidney biopsies between 2012 and 2013. Hematuria was defined as >3 or >10 red blood cells per high-power field (RBCs/hpf) in urine sediment. If >80% of the erythrocytes were dysmorphic, glomerular hematuria was diagnosed. Clinical findings and predictive value of dysmorphic erythrocytes were compared between patients with hematuria (n = 19) and those without (n = 61). The potential risk factors for hematuria among diabetic nephropathy patients were also screened. RESULTS: There was a statistically significant difference between the diabetic nephropathy group and the non-diabetic renal disease group (6.6 vs 16.8%; P = 0.04) when the demarcation point of hematuria was 10 RBCs/hpf. When the definition of hematuria was based on an examination of urinary erythrocyte morphology, a marked difference was seen (3.3 vs 24.8%; P < 0.001). Glomerular hematuria showed high specificity and a positive predictive value (0.97 and 0.94, respectively) in non-diabetic renal disease. A multivariate analysis showed that nephrotic syndrome was significantly associated with hematuria (odds ratio 3.636; P = 0.034). CONCLUSIONS: Dysmorphic erythrocytes were superior to hematuria for indicating non-diabetic renal disease in type 2 diabetics. Nephrotic syndrome was an independent risk factor for hematuria. PMID- 26812960 TI - Cancer mortality in the West Bank, Occupied Palestinian Territory. AB - BACKGROUND: The burden of cancer is difficult to study in the context of the occupied Palestinian territory because of the limited data available. This study aims to evaluate the quality of mortality data and to investigate cancer mortality patterns in the occupied Palestinian territory's West Bank governorates from 1999 to 2009. METHODS: Death certificates collected by the Palestinian Ministry of Health for Palestinians living in the West Bank were used. Direct and indirect age-standardised mortality rates were computed and used to compare different governorates according to total and specific cancer mortality. Furthermore, standardised proportional mortality ratios were calculated to compare mortality by urban, rural and camp locales. RESULTS: The most common cause of death out of all cancer types was lung cancer among males (22.8 %) and breast cancer among females (21.5 %) followed by prostate cancer for males (9.5 %) and by colon cancer for females (11.4 %). Regional variations in cancer specific causes of death were observed. The central- West Bank governorates had the lowest mortality for most cancer types among men and women. Mortality for lung cancer was highest in the north among men (SMR 109.6; 95%CI 99.5-120.4). For prostate cancer, mortality was highest in the north (SMR 103.6; 95%CI 88.5-120.5) and in the south (SMR 118.6; 95%CI 98.9-141.0). Breast cancer mortality was highest in the south (SMR 119.3; 95%CI 103.9-136.2). Similar mortality rate patterns were found in urban, rural and camp locales. CONCLUSION: The quality of the Palestinian mortality registry has improved over time. Results in the West Bank governorates present different mortality patterns. The differences might be explained by personal, contextual and environmental factors that need future in depth investigations. PMID- 26812961 TI - Wood reinforcement of poplar by rice NAC transcription factor. AB - Lignocellulose, composed of cellulose, hemicellulose, and lignin, in the secondary cell wall constitutes wood and is the most abundant form of biomass on Earth. Enhancement of wood accumulation may be an effective strategy to increase biomass as well as wood strength, but currently only limited research has been undertaken. Here, we demonstrated that OsSWN1, the orthologue of the rice NAC Secondary-wall Thickening factor (NST) transcription factor, effectively enhanced secondary cell wall formation in the Arabidopsis inflorescence stem and poplar (Populus tremula*Populus tremuloides) stem when expressed by the Arabidopsis NST3 promoter. Interestingly, in transgenic Arabidopsis and poplar, ectopic secondary cell wall deposition in the pith area was observed in addition to densification of the secondary cell wall in fiber cells. The cell wall content or density of the stem increased on average by up to 38% and 39% in Arabidopsis and poplar, respectively, without causing growth inhibition. As a result, physical strength of the stem increased by up to 57% in poplar. Collectively, these data suggest that the reinforcement of wood by NST3pro:OsSWN1 is a promising strategy to enhance wood-biomass production in dicotyledonous plant species. PMID- 26812962 TI - Contextual factors associated with uptake of breast and cervical cancer screening: A systematic review of the literature. AB - Existing research on barriers to breast and cervical cancer screening uptake has focused primarily on socio-demographic characteristics of individuals. However, contextual factors, such as service organization, as well as healthcare providers' training and practices, are more feasibly altered to increase health service use. The objective of the authors in this study was to perform a critical systematic review of the literature to identify contextual factors at the provider- and system-level that were associated with breast and cervical cancer screening uptake. Studies published from 2000 to 2013 were identified through PubMed and PsycInfo. Methodologic quality was assessed, and studies were examined for themes related to provider- and system-level factors associated with screening uptake. Thirteen studies met the inclusion criteria. Findings revealed a positive association between patients' receipt of provider recommendation and uptake of breast and cervical cancer screening. Uptake was also higher among patients of female providers. Facilities with flexible appointment times and reminders had higher mammography and Pap test uptake. Similarly, greater organizational commitment to quality and performance had higher breast and cervical cancer screening rates. Knowledge provided in this review could be used in future research to inform the development of public health policy and clinical programs to improve screening uptake. PMID- 26812964 TI - Headaches and hormones: a potentially lethal combination. PMID- 26812965 TI - Zebrafish as a Model for the Study of Chaperonopathies. AB - There is considerable information on the clinical manifestations and mode of inheritance for many genetic chaperonopathies but little is known on the molecular mechanisms underlying the cell and tissue abnormalities that characterize them. This scarcity of knowledge is mostly due to the lack of appropriate animal models that mimic closely the human molecular, cellular, and histological characteristics. In this article we introduce zebrafish as a suitable model to study molecular and cellular mechanisms pertaining to human chaperonopathies. Genetic chaperonopathies manifest themselves from very early in life so it is necessary to examine the impact of mutant chaperone genes during development, starting with fertilization and proceeding throughout the entire ontogenetic process. Zebrafish is amenable to such developmental analysis as well as studies during adulthood. In addition, the zebrafish genome contains a wide range of genes encoding proteins similar to those that form the chaperoning system of humans. This, together with the availability of techniques for genetic manipulations and for examination of all stages of development, makes zebrafish the organism of choice for the analysis of the molecular features and pathogenic mechanisms pertaining to human chaperonopathies. J. Cell. Physiol. 231: 2107 2114, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26812963 TI - Understanding the transmission dynamics of Leishmania donovani to provide robust evidence for interventions to eliminate visceral leishmaniasis in Bihar, India. AB - Visceral Leishmaniasis (VL) is a neglected vector-borne disease. In India, it is transmitted to humans by Leishmania donovani-infected Phlebotomus argentipes sand flies. In 2005, VL was targeted for elimination by the governments of India, Nepal and Bangladesh by 2015. The elimination strategy consists of rapid case detection, treatment of VL cases and vector control using indoor residual spraying (IRS). However, to achieve sustained elimination of VL, an appropriate post elimination surveillance programme should be designed, and crucial knowledge gaps in vector bionomics, human infection and transmission need to be addressed. This review examines the outstanding knowledge gaps, specifically in the context of Bihar State, India.The knowledge gaps in vector bionomics that will be of immediate benefit to current control operations include better estimates of human biting rates and natural infection rates of P. argentipes, with L. donovani, and how these vary spatially, temporally and in response to IRS. The relative importance of indoor and outdoor transmission, and how P. argentipes disperse, are also unknown. With respect to human transmission it is important to use a range of diagnostic tools to distinguish individuals in endemic communities into those who: 1) are to going to progress to clinical VL, 2) are immune/refractory to infection and 3) have had past exposure to sand flies.It is crucial to keep in mind that close to elimination, and post-elimination, VL cases will become infrequent, so it is vital to define what the surveillance programme should target and how it should be designed to prevent resurgence. Therefore, a better understanding of the transmission dynamics of VL, in particular of how rates of infection in humans and sand flies vary as functions of each other, is required to guide VL elimination efforts and ensure sustained elimination in the Indian subcontinent. By collecting contemporary entomological and human data in the same geographical locations, more precise epidemiological models can be produced. The suite of data collected can also be used to inform the national programme if supplementary vector control tools, in addition to IRS, are required to address the issues of people sleeping outside. PMID- 26812967 TI - Flavobacterium brevivitae sp. nov., isolated from river water. AB - A bacterial strain, designated TTM-43T, was isolated from a water sample taken from the Caohu River in Taiwan and characterized using a polyphasic taxonomic approach. Cells of strain TTM-43T were Gram-stain-negative, strictly aerobic, motile by gliding, rod-shaped and surrounded by a thick capsule. The strain formed bright-yellow colonies. Growth occurred at 15-30 degrees C (optimum, 20 degrees C), at pH 5-9 (optimum, pH 6) and with 0-0.3% NaCl (optimum growth in the absence of added NaCl). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain TTM-43T belonged to the genus Flavobacterium and was most closely related to Flavobacterium terrae R2A1-13T, with 97.8% sequence similarity. Strain TTM-43T contained iso-C15:0 (24.9%), iso-C15:1 G (12.6%), summed feature 9 (iso-C17:1omega9c and/or 10-methyl C16:0; 12.2%), iso-C17:0 3-OH (10.9%), iso-C15:0 3-OH (7.3%) and iso-C16:0 (6.7%) as the predominant fatty acids. The major isoprenoid quinone was MK-6. The polar lipid profile consisted of phosphatidylethanolamine and several uncharacterized aminophospholipids and phospholipids. The major polyamine was homospermidine. The genomic DNA G+C content of strain TTM-43T was 31 mol%. DNA-DNA relatedness of strain TTM-43T with respect to type strains of recognized species of the genus Flavobacterium was less than 70%. On the basis of phylogenetic inference and phenotypic data, strain TTM-43T should be assigned to a novel species, for which the name Flavobacterium brevivitae sp. nov. is presented. The type strain is TTM-43T (=BCRC 80913T=KCTC 42744T=LMG 29004T). PMID- 26812969 TI - [Clinicopathological features and survival of bone metastasis from primary hepatic carcinoma]. AB - OBJECTIVE: To explore clinicopathological features and prognostic factors of bone metastasis from primary hepatic carcinoma (PHC). METHODS: Eighty patients were enrolled with bone metastasis from PHC in Tianjin Medical University Cancer Institute and Hospital from January 2005 to June 2014 respectively. The clinicopathological features and prognostic factors of primary tumor were collected and bone metastases. Kaplan-Meier method was adopted for survival analysis. Log-rank method and Cox regression were used for univariate and multivariate analysis. RESULTS: The median survival was 4.7 (95% CI range from 3.4 to 6.0) months. The 6-, 12-, and 24-month survival was 42.5%, 17.5%, 2.5%, respectively. Univariate analysis indicated that Child-Pugh grading (P<0.01), ECOG score (P=0.014), serum cholinesterase (P=0.002), total bilirubin (P=0.006), ascites (P=0.003), TACE (P<0.01) were significant prognostic factors of survival. Multivariate analysis revealed that Child-Pugh classification (P<0.01), TACE (P<0.01) were independent prognostic factors of survival. CONCLUSION: Bone metastasis from PHC patients had poor survival. Patients can benefit from TACE and liver protecting treatment. PMID- 26812966 TI - Nanoparticle Attachment to Erythrocyte Via the Glycophorin A Targeted ERY1 Ligand Enhances Binding without Impacting Cellular Function. AB - PURPOSE: Nanoparticle (NP) attachment to biocompatible secondary carriers such as red blood cell (RBC) can prolong blood residence time of drug molecules and help create next-generation nanotherapeutics. However, little is known about the impact of RBC-targeted NPs on erythrocyte function. METHODS: The objectives of this study were to develop and characterize in vitro a novel poly-L-lysine (PLL) and polyethylene glycol (PEG) copolymer-based NP containing fluorescent-tagged bovine serum albumin (BSA), and conjugated with ERY1, a 12 amino acid peptide with high affinity for the RBC membrane protein glycophorin A (ENP). RESULTS: Confocal and flow cytometry data suggest that ENPs efficiently and irreversibly bind to RBC, with approximately 70% of erythrocytes bound after 24 h in a physiologic flow loop model compared to 10% binding of NPs without ERY1. Under these conditions, synthesized ENPs were not toxic to the RBCs. The rheological parameters at the applied shear. (0-15 Pa) were not influenced by ENP attachment to the RBCs. However, at high concentration, the strong affinity of ENPs to the glycophorin-A reduced the deformability of the RBC. CONCLUSIONS: ENPs can be efficiently attached to the RBCs without adversely affecting cellular function, and this may potentially enhance circulatory half-life of drug molecules. PMID- 26812970 TI - [Magnetic resonance guided focused ultrasound surgery for pain palliation of bone metastases: early experience of clinical application in China]. AB - OBJECTIVE: To evaluate the safety and efficacy of magnetic resonance guided focused ultrasound surgery (MRgFUS) in treatment for pain palliation of bone metastases. METHODS: Eighty-one patients of painful bone metastases were volunteered to screen for this study in Shanghai General Hospital from June 2014 to February 2015. Twenty-three patients among them were treated by MRgFUS, who was more than 18-years old, having the ability to fully understand the informed consent of the research, suffering with pain of numeric rating scale (NRS) >= 4, non-received radiotherapy or chemotherapy for pain palliation of bone metastases in the past two weeks. The NRS, the standard question of Brief Pain Inventory (BPI-QoL), and the standard question of Europe Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Bone Metastases 22 (EORTC QLQ BM22) were respectively recorded before and 1-week, 1-month, 3-month after the treatment. The related adverse events of MRgFUS were observed and recorded in 3 months after the treatment as well. RESULTS: (1)Twenty-three metastatic bone tumor lesions of 23 patients were treated by MRgFUS, the treatment data was as follows: the mean treatment time was (88 +/- 33) minutes, the mean sonication number was 13 +/- 8. (2) Adverse events included: pain in therapy area 3/23, which spontaneous relieving within one week; numbness in lower limb (1/23), which relieved after physiotherapy. (3) The NRS of before treatment and at 1-week, 1 month, and 3-month after treatment respectively was 6.0 +/- 1.5, 3.7 +/- 1.7,3.1 +/- 2.0, and 2.2 +/- 1.0,which significantly decreased after the treatment (P<0.01). (4) The BPI-QoL score of before treatment and at 1-week, 1-month, and 3 month after treatment respectively was 39 +/- 16, 27 +/- 18, 26 +/- 18, and 21 +/ 18, which significantly decreased after the treatment (P<0.01). (5) The EORTC QLQ-BM22 score of before treatment and at 1-week, 1-month, and 3-month after treatment respectively was 52 +/- 13, 44 +/- 12, 42 +/- 12, and 39 +/- 12, which also significantly decreased after the treatment (P<0.01). CONCLUSIONS: MRgFUS can be used as a non-invasive, safe, and effective method for treating painful bone metastases. Its clinical benefits of pain palliation and patient's quality of life improving are sustained after the treatment at least to 3 months. PMID- 26812968 TI - Elevated blood pressure in adolescent girls: correlation to body size and composition. AB - BACKGROUND: To improve understanding of the pathophysiology of hypertension in adolescents and pave the way for risk stratification, studies have sought to determine the correlates of blood pressure (BP). Inconsistencies in dependent and independent variables have resulted in an elusive consensus. The aim of this report is to examine an inclusive array of correlates of BP, as a continuous (systolic and diastolic BP) and a dichotomous variable. METHODS: Subjects were a school-based sample of 730 urban, mostly African American, non-referred 6th and 7th grade girls. To find independent correlates of SBP/DBP, we used a stepwise model selection method based on the Schwarz Bayesian Information Criterion, enabling selection of a parsimonious model among highly correlated covariates. Candidate variables were: age, stature, heart rate, pubertal development, BMI, BMI z-score, waist circumference, waist-to-height ratio (WHtR), body surface area, fat mass (by bioelectrical impedance analysis), fat-free mass (FFM), percentage of body fat, and presence of overweight/obesity. RESULTS: The best fitting models for DBP and SBP (considered separately) included fat-free mass, heart rate and, in the case of SBP, stature. The best-fitting model for high normal/elevated blood pressure (H-N/EBP) included WHtR with no independent relation of any other variable. The prevalence of H-N/EBP tripled between a WHtR of 0.5 and 0.7. CONCLUSIONS: The easily obtained and calculated WHtR is the strongest correlate of elevated blood pressure among available variables and is a prime candidate for longitudinal studies of predictors of the development of hypertension. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT00746083. PMID- 26812971 TI - [Virtual unehanced image in the single-source dual energy CT for evaluation of renal cell carcinoma:a preliminary study]. AB - OBJECTIVE: To qualitatively and quantitatively evaluate the feasibility of CT virtual unenhanced (VUE) spectral imaging in renal cell carcinoma. METHOD: Thirty six patients with histopathologically proven renal cell carcinoma underwent gemstone spectral imaging (GSI) including ture unenhanced (TUE), arterial, cortex and medullary phase acquisitions. The triphasic GSI dataset was sent to workstation and 3 sets of VUE images (including VUE a, VUE c, VUE m) were obtained by subtract iodine from iodine-water images in the triphasic enhanced GSI images, respectively. The quality of VUE s and TUE images was evaluated on a five-point scale.Interobserver agreement with regard to image quality was assessed using Cohen's Kappa, and four groups of image quality was compared with ANOVA analysis. The contrast-to-noise ratio (CNR) of mass-to-kidney in the TUE and VUE s images was calculated, and difference between these four datasets was compared with ANOVA analysis. Using appearance of masses on triphasic images as a standard, the masses detection ratio of four groups was calculated and compared with chi-square test. RESULTS: Interobserver agreement with regard to image quality was excellent (kappa>0.600). There was no significant difference among the image quality of TUE and triphasic images of VUEs (P>0.05). The CNR of TUE (0.7 +/- 0.6) was significant worse than that of triphasic images (1.7 +/- 1.0, 1.9 +/- 1.2, 2.5 +/- 1.4, respectively) (P<0.05). There was no significant difference among the CNR of triphasic images (P>0.05). CONCLUSION: VUE images obtain from triphasic phases may be a surrogate for conventional unenhanced scan in renal cell carcinoma diagnosis. PMID- 26812972 TI - [Prevalence, severity, characteristics and coronary calcified score of coronary artery plaques are different in women than men with suspected coronary artery disease]. AB - OBJECTIVE: To validate the prevalence, severity, characteristics and coronary calcified score(CACS) of coronary artery plaques in women are different from men. METHODS: A total of 3 752 patients with suspected coronary artery disease in the First Affiliated Hospital of China Medical University were enrolled between September 2011 and December 2013. Patients with suspect CAD underwent 256 detecter coronary computed tomography (CCTA) and CACS measurement were enrolled. The differences of sex-associated coronary artery plaques were assessed. The univariable and multivariable Logistic regression were employ to assess the association female and male with coronary artery plaques. RESULTS: A total of 3 752 patients including 1 832 females and 1 920 males, the average age of the patients was (56 +/- 11) years. Women were older and less smoker than men. The prevalences of any plaque, 2-,3-/LM disease and significant/severe stenosis significantly decreased in female than male (all P<0.01). The proportion of non calcified plaques significantly higher and mixed plaque significantly lower in female than male (all P<0.01). the proportion of women were significantly lower than men in CACS>0 (all P<0.01). The similar tendency also happened in four age matched female and male subgroups. After adjustment, female was the significant protective factor for significant and severe stenosis, 2- and 3-/LM vessel disease, calcified and mixed plaques, and CACS>100 (all P<0.01); female was the significant protective factor for non-calcified plaques in the univariate analysis (P<0.01). When the age >= 65, female became the significant risk factor for coronary artery plaques (all P<0.01). CONCLUSIONS: Women have less prevalence and extensive coronary artery plaques and lower CACS, the plaque characteristics in women is more frequently composed by non-calcified plaques than men, even after matched by age. With age, female change from a protective factor to a risk factor for coronary artery plaques. PMID- 26812973 TI - [Case-control study of expansion of heart cavity and great vessel diameters in acromegaly]. AB - OBJECTIVE: To investigate alternations of heart cavity and great vessel diameters and their risk factors in acromegalic patients. METHODS: Ninety-two cases, diagnosed as acromegaly, were selected as research subjects from January 2013 to December 2013 in Peking Union Medical College Hospital. There were 37 males and 55 females with an average age of 41.2 years (SD, 12.5 years, range from 19 to 67 years old). Ninety-two sex and age matched healthy individuals were selected as controls. Disease history, echocardiography, endocrine hormone levels were collected to make contractive analysis. We analyzed the related risk factors of great vessel diameters expansion with binary logistic regression analysis and finally obtained the OR (odd ratio) and predictive formula. RESULTS: Left ventricle end-diastolic diameter (LVEDD), left ventricle end-systolic diameter (LVESD), left atrium longitudinal dimension (LALD), right ventricle longitudinal dimension (RVLD), aortic root dimension (AORD), ascending aorta (AA), main pulmonary artery (MPA) were higher in patients with acromegaly than in healthy people, P<0.05. The comparison between expanded vessel diameters and normal vessel diameters in acromegalics showed that difference of disease duration was of statistical significance, OR= 1.011. We got the formula: logit (ADE)= 3.420+0.011 * duration of disease. CONCLUSION: Heart cavity and vessel diameters in acromegalic patients were higher than that in public. Expanding of great vessel diameters mainly depend on duration of disease instead of serum GH and IGF 1 level, and the duration of disease is the risk factor of the expansion of great vessel diameters. PMID- 26812974 TI - [Pulmonary ultrasound guidance of congenital heart disease postoperative ventilator applications]. AB - OBJECTIVE: To investigate the pulmonary ultrasound in children with congenital heart disease postoperative invasive ventilator time, non-invasive ventilator use the guide. METHODS: Using prospective clinical observation research methods, Randomly divide 100 cases ranged from 6 months to 3 years old in cardiopulmonary bypass after congenital heart disease surgery patients into ultrasound group and control group, 50 cases in each group. All postoperative give positive cardiac function maintenance, diuresis, etc. Ultrasound group adopted the pulmonary ultrasound in children with pulmonary interstitial pulmonary edema monitoring and guide to extubation, enable the timing of the noninvasive ventilator support; Control group based on the bedside chest X-ray lung condition. Compare two groups of children with mechanical ventilation time (including the invasive and noninvasive ventilator support), noninvasive ventilator utilization rate and its accuracy, start the noninvasive ventilator time, the incidence of ventilator associated pneumonia (VAP), secondary tracheal intubation cases and ICU stay time, etc. RESULTS: The ultrasound group compared with the control group in Invasive ventilator time [(15.0 +/- 11.0) vs (20.0 +/- 13.5, P=0.043)], noninvasive ventilation time [(38.5 +/- 11.8) vs (48.6 +/- 21.9, P=0.032)], the number of cases of the use of noninvasive ventilation (10 cases vs 22 cases, P=0.041), the correct use of the number of cases (10 vs 14, P=0.034) and VAP cases (3 vs 8, P=0.044), there was statistical significance, P< 0.05. The ultrasound group of children with ICU stay time was significantly lower than the control group [(66.0 +/- 38.9) vs (82.0 +/- 42.4, P=0.038)]; Control group had 2 cases with secondary tracheal intubation, ultrasound group one, comparing the two groups has no statistical significance (P> 0.05). CONCLUSION: Postoperative children with congenital heart disease using pulmonary ultrasound evaluation of pulmonary interstitial edema,guide the ventilator, it can effectively shorten (invasive and noninvasive mechanical ventilation time and ICU length of hospital stay, lung ultrasound has instant, noninvasive, No radiation, repeatable,pulmonary ultrasound will be important after cardiopulmonary bypass interstitial lung edema diagnosis, evaluation of treatment means and helps to treat critically ill children. PMID- 26812975 TI - [Influence of ODD diagnosis on the association between NET1 and attention deficit/hyperactivity disorder]. AB - OBJECTIVE: To explore the association between the SNP rs3785143 of NET1 gene and attention-deficit/hyperactivity disorder (ADHD) with and without oppositional defiant disorder (ODD). METHODS: Five hundreds and eighty-seven ADHD children with ODD, 1228 ADHD children without ODD and 554 healthy children were recruited from child psychiatric clinics of Peking University Sixth Hospital/Institute of Mental Health and included for genotyping of rs3785143. Comparisons of allelic and genotypic distribution among these groups were conducted. RESULTS: In ADHD children with ODD, the genotypic distribution was significantly different from controls (P=0.008), showing higher TT frequency in ADHD with ODD (4.3% vs 1.6%, P=0.009). In ADHD children without ODD, the C allele (0.859 vs 0.821, P=0.005) and CC genotype (73.4% vs 65.9%, P=0.001) showed higher frequencies than controls. After controlling the potential influence of age and gender, those associations were retained. To further exclude the potential effect of other comorbidities, we repeated above analyses in pure ADHD and pure ADHD with ODD. In pure ADHD, the C allele (0.870 vs 0.821, P=0.003) and CC genotype (75.8% vs 65.9%, P=0.001) showed higher frequencies than controls; while in pure ADHD with ODD, the TT genotype showed higher frequency than controls (5.1% vs 1.6%, P=0.006). CONCLUSIONS: We replicate the association between the SNP rs3785143 of NET1 gene and ADHD by case-control study.There may be different genetic mechanisms between ADHD with and without ODD. PMID- 26812976 TI - [Study on changes of plasma levels of oxidative stress biomarkers and its relation with cognition function in patients with parkinson's disease]. AB - OBJECTIVE: To study the changes of plasma levels of oxidative stress biomarkers in patients with parkinson's disease (PD), and to explore its association with cognition function. METHODS: Seventy-two PD patients from June 2013 to May 2012 were enrolled. All of them were outpatients or inpatients at the First Affiliated Hospital of Nanjing Medical University. And forty-five age- and gender- matched healthy subjects were used as controls. The information including gender, age, illness duration, years of education and Hoehn & Yahr (H-Y) stage were recorded. Cognition function of all the patients with PD and the controls were measured by using Montreal Cognitive Assessment (MoCA) scale. Plasma levels of catalase (CAT), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), total glutathione (T-GSH) and malondialdehyde (MDA) were measured by ELISA . Then we compared and analyzed the results. RESULTS: Plasma levels of CAT, T-SOD and T-GSH in PD group were significantly lower than the control group [(159 +/- 9) kU/L vs (170 +/- 5) kU/L, P< 0.01; (97 +/- 24) kU/L vs (124 +/- 25) kU/L, P<0.01; (17 +/- 10) umol/L vs (60 +/- 51) umol/L, P< 0.01]. Plasma levels of CAT, T-GSH, GSH-Px and MDA were no differences between early PD group (H-Y stage I-II) and middle late PD group (H-Y stage III or higher) of patients (P>0.05). Plasma levels of T GSH in PD group with mild cognitive impairment (MCI) were obviously lower than PD group without MCI [(14 +/- 7) umol/L vs (19 +/- 11) umol/L, P< 0.05]. In PD patients, MoCA scores were positively correlated with years of education (beta=0.634, P= 0.000) and plasma levels of T-GSH (beta= 0.204, P= 0.014), and were negatively correlated with H-Y stage (beta=-0.194, P=0.020). CONCLUSIONS: The damage of plasma antioxidant mechanism may be involved in the pathogenesis of patients with PD. Decrease in plasma levels of T-GSH may be associated with MCI in PD patients . Plasma levels of T-GSH may be a potential early predictive index in PD patients with cognitive dysfunction. PMID- 26812977 TI - [Analysis of serum lipid level in patients with multiple system atrophy]. AB - OBJECTIVE: To explore the serum levels of lipids and lipoproteins in patients with multiple system atrophy (MSA). METHODS: From July 2009 to June 2014, a total of 62 MSA patients from the neurology department of our hospital were enrolled as the case group and 63 healthy individuals were enrolled as control group. The serum levels of lipids and lipoproteins were compared between two groups and also analyzed according to gender, age and disease subtypes. RESULTS: Compared with the healthy controls, abnormal rates of high density lipoprotein cholesterol (HDL C), apolipoproteins A (ApoA) and apolipoproteins B (ApoB) in MSA patients were decreased significantly (P<0.01), while there is no difference of abnormal rates in TC, TG and LDL-C. Compared with the healthy controls, the serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), LDL-C, ApoA and ApoB levels in MSA patients were decreased significantly (P<0.01). There was no significant difference in TG levels. Compared with female MSA patients, the serum TG and LDL-C in male MSA patients were decreased significantly (P<0.05). Compared with male controls, TC, LDL-C, HDL-C, ApoA and ApoB levels of male MSA patients were decreased significantly (P<0.05) whilst there was no significant difference in TG level (P>0.05). Compared with female controls, the serum TC,TG, HDL-C, ApoA and ApoB levels in female MSA patients were decreased significantly (P<0.05) whilst there was no significant difference in LDL-C (P>0.05). There was no significant difference in lipid levels between elder patients (age over 65) and younger patients (age under 65) (P>0.05). Also no significant difference existed between type C and type P of MSA (P>0.05). No significant relationship between course of disease and lipids was found (P>0.05). CONCLUSION: Serum levels of TC, HDL-C, LDL-C, ApoA and ApoB are decreased in MSA patients but all lipid levels are not related to either disease course or subtype, which may indicate that lipids levels are related to the pathogenesis of MSA. PMID- 26812978 TI - [Investigation of osteoporosis prevalence and osteoporosis-related clinical risk factors among healthy elderly male]. AB - OBJECTIVE: To investigate the osteoporosis prevalence and osteoporosis-related clinical risk factors among healthy elderly male. METHODS: A cross-sectional study was conducted from January 2014 to October 2014. Healthy elderly male aged 50 and above from Beijing WangZuo Community who had completed the questionnaire we made were enrolled in this study and accepted bone mineral density (BMD) testing by dual energy X-ray absorptiometry. Subjects were classified as the osteoporosis group (OP group) and the non-osteoporosis group (Non-OP group) according to the WHO criteria, of which osteoporosis was defined arbitrarily when any T-score was -2.5 standard deviations or less at femoral neck, total hip or lumbar spine (L1-4). The clinical risk factors of each subject including age, body weight, Body Mass Index (BMI), previous fragility fracture history, smoking, alcohol abuse, glucocorticoid therapy and other capable clinical risk factors were collected and compared in OP group and Non-OP group. RESULTS: In the 346 cases of elderly healthy men, 18.5% had osteoporosis, 55.5% had osteopenia and 26.0% were normal. Femoral neck's and total hip's BMD level decreased with increasing age. However, the trend was not found at lumbar spine site. There appeared to be a significant difference in BMD standard between lumbar vertebral and total hip when compared with age-matched cohorts (P<0.05). Weight, BMI, previous fragility fracture history and smoking were found significant differences between OP group and Non-OP group (P<0.05). CONCLUSIONS: The prevalence of osteoporosis in healthy older men should not be ignored. Low BMI and weight, previous fragility fracture history and smoking history were clinical risk factors of OP in this population. PMID- 26812979 TI - [Characteristic and treatment of acute aggravating cubital tunnel syndrome]. AB - OBJECTIVE: To investigate the causes and the characteristics of acute aggravating cubital tunnel syndrome. METHODS: The enrolling criteria of subjects were as follows: (1) Patients with manifestation of cubital tunnel syndrome for more than 6 months; (2) acute exacerbation of the disease for no more than 4 weeks. The clinical data from March 2011 to December 2014 was collected and analyzed retrospectively. Twelve cases aged 52 to 65 met the enrolling criteria and were included in this study, and among them 10 patients were male, 2 were female; 5 cases were on the left and the other 7 on the right. All of them had some degree of cubital tunnel syndrome symptoms before the onset of acute exacerbation. RESULTS: When nerve decompression and anterior transposition of the ulnar nerve was performed, the elbow joint cysts which squeezed the ulnar nerve were found. The cysts were then resected. In all 12 cases, the compression symptoms of ulnar nerve were relieved after surgery. The mean follow up period was 13 months, ranging from 6 to 45 months. According to Gu Yudong functional evaluation criteria for cubital tunnel syndrome, 2 of the patients can be judged as "Excellent", 8 "good" and 2 "acceptable" at the follow-up. CONCLUSIONS: Cyst compression may induce the acute exacerbation of ulnar nerve symptom in patients with cubital tunnel syndrome. Early diagnosis and treatment is critical for these patients. PMID- 26812980 TI - [Change and Significance of RhoA/ROCK signaling pathway in the model with natural degeneration of the rat endplate chondrocytes]. AB - OBJECTIVE: To explore the change and Significance of RhoA/ROCK signaling pathway in the model with natural degeneration of the rat endplate chondrocytes. METHODS: Endplate chondrocytes were selected by enzyme digestion and cultured in vitro to divided into control (P2 cells), naturally passaged (P5 cells) groups and treatment group (P5+ROCK Inhibitor Y27632). The phenotype of endplate chondrocytes were identified by toluidine blue stains and F-actin stains. Type II collagen, aggrecan and SOX9 genes were examed by Real-time RT-PCR to verify the degeneration model. The RhoA/ROCK signaling pathway related gene ROCK-1, ROCK-2 were detected by RT-PCR and Western blot. The actived RhoA was examed by active RhoA detection and Western blot. RESULTS: With the passaging,endplate chondrocytes completely lost the original cell morphology, the levels of type II collagen (P5/P2=0.248, P<0.001), aggrecan (P5/P2=0.172, P<0.001) and SOX9 (P5/P2 =0.499, P<0.001) significantly reduced. There is also a certain reduction of ROCK 1 (P5/P2=0.652, P<0.001), but ROCK-2 (P5/P2=2.527, P<0.001) expression increased significantly. And the active-RhoA were Significant increased too.ROCK-1 AND ROCK 2 were down-regulated in the treatment group. And type II collagen, aggrecan, SOX9 significantly increased. CONCLUSION: The degeneration of endplate chondrocytes with decreased ROCK-1 expression but increased active-RhoA and ROCK 2 expression suggest that RhoA/ROCK signaling pathway play an important role in the in vitro degeneration of endplate chondrocytes.Modulating the expression of RhoA/ROCK signaling pathway may be a new method of solving the problem of the degeneration of intervertebral disc. PMID- 26812981 TI - [The safety and efficacy of endoscopic versus microscopic surgery for transsphenoidal pituitary adenoma in China: an updated and cumulative meta analysis]. AB - OBJECTIVE: To evaluate the present clinical effectiveness and its change trend by an updated and cumulative meta-analysis of endoscopic versus microscopic surgery for transsphenoidal pituitary adenoma in China. METHODS: We conducted a systematic review of the literature related to theme,and the meta-analysis of the data extracted onto a standard form was conducted by State 12.0 software. RESULTS: Finally 14 studies were included. There were 1 888 patients in total including 962 patients receiving endoscopic surgery and 926 patients undergoing microscopic surgery. Compared with microscopic group,there were significant advantages in endoscopic group including the high rate of complete tumor resection (OR=1.951, 95% CI: 1.525-2.495) and the lower incidence of overall operation complication (OR=0.480, 95% CI: 0.298-0.773) and cerebrospinal fluid leakage (OR=0.592, 95% CI: 0.399-0.878), but the advantage of the incidence rate of diabetes insipidus (OR=0.72, 95% CI: 0.420-1.252) was no statistically significant. Cumulative meta-analysis suggested that the advantage of total resection of tumor has stabilized in 2013. CONCLUSION: At present in our country, compared with microscopic group, there were significant advantages in endoscopic group including the rate of complete tumor resection and the incidence of overall operation complications and cerebrospinal fluid leakage, but the advantage of the incidence rate of diabetes insipidus was no statistically significant difference. The follow-up studies related to the rate of total resection of tumor may not change the existing meta-analysis results. PMID- 26812982 TI - Effect of Temporary Meiotic Attenuation of Oocytes with Butyrolactone I and Roscovitine in Resistance to Bovine Embryos on Vitrification. AB - This study aimed to produce in vitro bovine embryos by the addition of two drugs, which is responsible for oocyte meiosis inhibition: roscovitine (ROS) and butyrolactone I (BL-I). Oocytes were recovered from slaughtered cows and matured in a commercial medium and maintained in a 5% CO2 atmosphere. Oocytes were maintained for 6 h in an in vitro maturation (IVM) medium containing ROS (12.5 MUm), BL-I (50 MUm) and association of drugs (ROS 6.25 MUm and BL-I 25 MUm). Oocytes were cultured for 18 h in an agent-free medium for the resumption of meiosis. After 24 h of maturation, oocytes were inseminated in the commercial in vitro fertilization (IVF) medium. Presumptive zygotes were cultured in SOFaa medium in a 5% CO2 atmosphere. On day 3, rate of cleavage was evaluated and on days 6 and 7, rate of blastocyst formation. BL-I and its association with the ROS increased the rates of cleavage and blastocyst formation (p < 0.05). The ROS alone was inefficient, impairing embryonic development, with low rates of blastocyst formation when compared to the control group and other treatments (p < 0.05). The embryos from BL-I and ROS+BL-I groups presented higher number of cells and lower rates of cellular apoptosis compared to other groups, either for the fresh or for post-thawing embryos. Embryos from ROS+BL-I group showed to be more resistant to the vitrification process, presenting a higher rate of embryonic re expansion (p < 0.05). In conclusion, block of meiosis using BL-I or its association with ROS increased the rate of blastocyst formation, and the association of ROS+BL-I resulted in a better resistance to the embryo cryopreservation process. PMID- 26812983 TI - CD-MOF: A Versatile Separation Medium. AB - Porous metal-organic frameworks (MOFs) have been studied in the context of a wide variety of applications, particularly in relation to molecular storage and separation sciences. Recently, we reported a green, renewable framework material composed of gamma-cyclodextrin (gamma-CD) and alkali metal salts--namely, CD-MOF. This porous material has been shown to facilitate the separation of mixtures of alkylaromatic compounds, including the BTEX mixture (benzene, toluene, ethylbenzene, and the regioisomers of xylene), into their pure components, in both the liquid and gas phases, in an energy-efficient manner which could have implications for the petrochemical industry. Here, we report the ability of CD MOF to separate a wide variety of mixtures, including ethylbenzene from styrene, haloaromatics, terpinenes, pinenes and other chiral compounds. CD-MOF retains saturated compounds to a greater extent than their unsaturated analogues. Also, the location of a double bond within a molecule influences its retention within the extended framework, as revealed in the case of the structural isomers of pinene and terpinine, where the isomers with exocyclic double bonds are more highly retained than those with endocyclic double bonds. The ability of CD-MOF to separate various mono- and disubstituted haloaromatic compounds appears to be controlled by both the size of the halogen substituents and the strength of the noncovalent bonding interactions between the analyte and the framework, an observation which has been confirmed by molecular simulations. Since CD-MOF is a homochiral framework, it is also able to resolve the enantiomers of chiral analytes, including those of limonene and 1-phenylethanol. These findings could lead to cheaper and easier-to-prepare stationary phases for HPLC separations when compared with other chiral stationary phases, such as CD-bonded silica particles. PMID- 26812984 TI - Fondaparinux: another potential treatment for heparin-induced thrombocytopenia type II? PMID- 26812985 TI - Advancing sports and exercise genomics: moving from hypothesis-driven single study approaches to large multi-omics collaborative science. PMID- 26812986 TI - Biosynthesis of milk fat, protein, and lactose: roles of transcriptional and posttranscriptional regulation. AB - The demand for high-quality milk is increasing worldwide. The efficiency of milk synthesis can be improved by taking advantage of the accumulated knowledge of the transcriptional and posttranscriptional regulation of genes coding for proteins involved in the synthesis of fat, protein, and lactose in the mammary gland. Research in this area is relatively new, but data accumulated in the last 10 years provide a relatively clear picture. Milk fat synthesis appears to be regulated, at least in bovines, by an interactive network between SREBP1, PPARgamma, and LXRalpha, with a potential role for other transcription factors, such as Spot14, ChREBP, and Sp1. Milk protein synthesis is highly regulated by insulin, amino acids, and amino acid transporters via transcriptional and posttranscriptional routes, with the insulin-mTOR pathway playing a central role. The transcriptional regulation of lactose synthesis is still poorly understood, but it is clear that glucose transporters play an important role. They can also cooperatively interact with amino acid transporters and the mTOR pathway. Recent data indicate the possibility of nutrigenomic interventions to increase milk fat synthesis by feeding long-chain fatty acids and milk protein synthesis by feeding amino acids. We propose a transcriptional network model to account for all available findings. This model encompasses a complex network of proteins that control milk synthesis with a cross talk between milk fat, protein, and lactose regulation, with mTOR functioning as a central hub. PMID- 26812990 TI - The editorial term of Sir John Ellis (Volumes 1-9). PMID- 26812987 TI - Differential DNA methylation patterns of homeobox genes in proximal and distal colon epithelial cells. AB - Region and cell-type specific differences in the molecular make up of colon epithelial cells have been reported. Those differences may underlie the region specific characteristics of common colon epithelial diseases such as colorectal cancer and inflammatory bowel disease. DNA methylation is a cell-type specific epigenetic mark, essential for transcriptional regulation, silencing of repetitive DNA and genomic imprinting. Little is known about any region-specific variations in methylation patterns in human colon epithelial cells. Using purified epithelial cells and whole biopsies (n= 19) from human subjects, we generated epigenome-wide DNA methylation data (using the HELP-tagging assay), comparing the methylation signatures of the proximal and distal colon. We identified a total of 125 differentially methylated sites (DMS) mapping to transcription start sites of protein-coding genes, most notably several members of the homeobox (HOX) family of genes. Patterns of differential methylation were validated with MassArray EpiTYPER. We also examined DNA methylation in whole biopsies, applying a computational technique to deconvolve variation in methylation within cell types and variation in cell-type composition across biopsies. Including inferred epithelial proportions as a covariate in differential methylation analysis applied to the whole biopsies resulted in greater overlap with the results obtained from purified epithelial cells compared with when the covariate was not included. Results obtained from both approaches highlight region-specific methylation patterns of HOX genes in colonic epithelium. Regional variation in methylation patterns has implications for the study of diseases that exhibit regional expression patterns in the human colon, such as inflammatory bowel disease and colorectal cancer. PMID- 26812991 TI - Revisiting 'Measuring the process of solving clinical diagnostic problems'. PMID- 26812988 TI - Effect of Breed on Plasma Endothelin-1 Concentration, Plasma Renin Activity, and Serum Cortisol Concentration in Healthy Dogs. AB - BACKGROUND: There are breed differences in several blood variables in healthy dogs. OBJECTIVE: Investigate breed variation in plasma endothelin-1 (ET-1) concentration, plasma renin activity, and serum cortisol concentration. ANIMALS: Five-hundred and thirty-one healthy dogs of 9 breeds examined at 5 centers (2-4 breeds/center). METHODS: Prospective observational study. Circulating concentrations of ET-1 and cortisol, and renin activity, were measured using commercially available assays. Absence of organ-related or systemic disease was ensured by thorough clinical investigations, including blood pressure measurement, echocardiography, ECG, blood and urine analysis. RESULTS: Median ET 1 concentration was 1.29 (interquartile range [IQR], 0.97-1.82) pg/mL, median cortisol concentration 46.0 (IQR, 29.0-80.8) nmol/L, and median renin activity 0.73 (IQR, 0.48-1.10) ng/mL/h in all dogs. Overall, breed differences were found in ET-1 and cortisol concentrations, and renin activity (P < .0001 for all). Pair wise comparisons between breeds differed in 67% of comparisons for ET-1, 22% for cortisol, and 19% for renin activity, respectively. Within centers, breed differences were found at 5/5 centers for ET-1, 4/5 centers for cortisol, and 2/5 centers for renin activity. Newfoundlands had highest median ET-1 concentration, 3 times higher than Cavalier King Charles Spaniels, Doberman Pinschers, and Dachshunds. Median renin activity was highest in Dachshunds, twice the median value in Newfoundlands and Boxers. Median cortisol concentration was highest in Finnish Lapphunds, almost 3 times higher than in Boxers. CONCLUSIONS AND CLINICAL IMPORTANCE: Breed variation might be important to take into consideration when interpreting test results in clinical studies. PMID- 26812992 TI - Socio-material theory: an alternate view of interprofessional team learning. PMID- 26812993 TI - Is medical education ready to embrace the socio-material? PMID- 26812994 TI - The complex relationship between student, context and learning outcomes. PMID- 26812995 TI - When I say... culture. PMID- 26812996 TI - Socio-material perspectives on interprofessional team and collaborative learning. AB - CONTEXT: Interprofessional teamwork and collaboration have become important parts of health care practice and education. Most of the literature on interprofessional learning, however, assumes that learning is something acquired by individuals and readily transferred to other contexts. This assumption severely limits the ways in which interprofessional educators and researchers can conceptualise and support learning related to collaborative interprofessional health care. Socio-material theories provide an alternative to individualistic, acquisition-oriented notions by reconceiving learning in terms of collective dynamics, participation in social communities and active engagement with material contexts. METHODS: Socio-material literature and theories were reviewed to identify concepts relevant to interprofessional learning. After briefly summarising the origins and key principles of socio-material approaches, the authors draw upon specific socio-material theories--including complexity theory, cultural-historical activity theory and actor-network theory--in order to reconceive how learning happens in interprofessional contexts. This reframing of interprofessional learning focuses less on individuals and more on collective dynamics and the actual social and material relations involved in practice. DISCUSSION: The paper proposes five ways in which learning may be enacted in interprofessional teamwork and collaboration from a socio-material perspective: (i) diverse contributions; (ii) social interactions and relationships; (iii) synthesis of professional ideas; (iv) integration of material elements, and (v) connections to large-scale organisations. For each of these categories, the paper provides practical illustrations to assist educators and researchers who wish to identify and assess this learning. CONCLUSIONS: Although more exploratory than comprehensive, this paper articulates many key aspects of socio-material learning theories and offers practical guidance for those who wish to employ and assess them in interprofessional contexts. PMID- 26812997 TI - Does source matter? Nurses' and Physicians' perceptions of interprofessional feedback. AB - OBJECTIVE: Receptiveness to interprofessional feedback, which is important for optimal collaboration, may be influenced by 'in-group or out-group' categorisation, as suggested by social identity theory. We used an experimental design to explore how nurses and resident physicians perceive feedback from people within and outside their own professional group. METHODS: Paediatric residents and nurses participated in a simulation-based team exercise. Two nurses and two physicians wrote anonymous performance feedback for each participant. Participants each received a survey containing these feedback comments with prompts to rate (i) the usefulness (ii) the positivity and (iii) their agreement with each comment. Half of the participants received feedback labelled with the feedback provider's profession (two comments correctly labelled and two incorrectly labelled). Half received unlabelled feedback and were asked to guess the provider's profession. For each group, we performed separate three-way anovas on usefulness, positivity and agreement ratings to examine interactions between the recipient's profession, actual provider profession and perceived provider profession. RESULTS: Forty-five out of 50 participants completed the survey. There were no significant interactions between profession of the recipient and the actual profession of the feedback provider for any of the 3 variables. Among participants who guessed the source of the feedback, we found significant interactions between the profession of the feedback recipient and the guessed source of the feedback for both usefulness (F1,48 = 25.6; p < 0.001; eta(2) = 0.35) and agreement ratings (F1,48 = 8.49; p < 0.01; eta(2) = 0.15). Nurses' ratings of feedback they guessed to be from nurses were higher than ratings of feedback they guessed to be from physicians, and vice versa. Among participants who received labelled feedback, we noted a similar interaction between the profession of the feedback recipient and labelled source of feedback for usefulness ratings (F1,92 = 4.72; p < 0.05; eta(2) = 0.05). CONCLUSION: Our data suggest that physicians and nurses are more likely to attribute favourably perceived feedback to the in-group than to the out-group. This finding has potential implications for interprofessional feedback practices. PMID- 26812998 TI - What do UK doctors in training value in a post? A discrete choice experiment. AB - CONTEXT: Many individual and job-related factors are known to influence medical careers decision making. Medical trainees' (residents) views of which characteristics of a training post are important to them have been extensively studied but how they trade-off these characteristics is under-researched. Such information is crucial for the development of effective policies to enhance recruitment and retention. Our aim was to investigate the strength of UK foundation doctors' and trainees' preferences for training post characteristics in terms of monetary value. METHODS: We used an online questionnaire study incorporating a discrete choice experiment (DCE), distributed to foundation programme doctors and doctors in training across all specialty groups within three UK regions, in August-October 2013. The main outcome measures were monetary values for training-post characteristics, based on willingness to forgo and willingness to accept extra income for a change in each job characteristic, calculated from regression coefficients. RESULTS: The questionnaire was answered by 1323 trainees. Good working conditions were the most influential characteristics of a training position. Trainee doctors would need to be compensated by an additional 49.8% above the average earnings within their specialty to move from a post with good working conditions to one with poor working conditions. A training post with limited rather than good opportunities for one's spouse or partner would require compensation of 38.4% above the average earnings within their specialty. Trainees would require compensation of 30.8% above the average earnings within their specialty to move from a desirable to a less desirable locality. These preferences varied only to a limited extent according to individual characteristics. DISCUSSION: Trainees place most value on good working conditions, good opportunities for their partners and desirable geographical location when making career-related decisions. This intelligence can be used to develop alternative models of workforce planning or to develop information about job opportunities that address trainees' values. PMID- 26812999 TI - Students' goal orientations, perceptions of early clinical experiences and learning outcomes. AB - CONTEXT: Workplace learning is optimised when learners engage in the activities of the workplace; learner engagement is influenced by workplace affordances and learner agency. Learner agency can be operationalised through achievement goal theory, which explains that students can have different goal orientations as they enter learning situations: mastery (learn and improve), performance approach (demonstrate competence) or performance-avoid (avoid demonstrating incompetence). Mastery-orientated, compared with performance-orientated, students approach curricular experiences as opportunities for developing rather than demonstrating competence. This study explored the relationships among students' achievement goal orientations, workplace affordances and learning outcomes in the context of early clinical experiences. METHODS: Students who completed their preclerkship curricula at four medical schools answered a questionnaire about their personal goal orientation and the perceived goal structure and workplace affordances of their preceptorship experiences. All items used a 5-point scale (1 = strongly disagree/not at all true, 5 = strongly agree/very true). Students were evaluated by their preceptors and completed standardised-patient exams at the end of their pre-clerkship curricula. Analyses included descriptive statistics and mediation analysis. RESULTS: Of 517 students, 296 (57.3%) responded and 253 (85.5%) had linked performance data. Student goal orientation means were: mastery, mean = 4.27 (SD = 0.65); performance-approach, 2.41 (0.76); performance-avoid, 2.84 (0.88). Student goal orientation and performance on preceptor evaluations (PEval) or standardised-patient exams (SPExam) were not significantly related. Perceptions of a mastery-structured curriculum and inviting workplace were associated with higher SPExam (beta = 0.28, p = 0.02) and PEval (beta = 0.51, p = 0.00) scores, respectively. Student mastery goal orientation was positively associated with perceptions of a mastery-structured curriculum (beta = 0.59, p = 0.00) and positive workplace affordances (beta = 0.25-0.29, p <= 0.01). CONCLUSIONS: Students held a predominant mastery goal orientation towards their early clinical experiences. Mastery-orientated students perceived preceptorships as mastery-structured with positive workplace affordances, and those perceiving a mastery-structured or inviting preceptorship performed better. Clinical experiences should be structured to emphasise learning rather than demonstration of skills to promote learning outcomes. PMID- 26813000 TI - Changes in the preferences of US physicians-in-training for medical interventions throughout medical education. AB - CONTEXT: There exists a disparity between the views of physicians and the views of their patients on end-of-life decisions. However, the timing of when the end of-life preferences of physicians and non-medically-trained individuals diverge is currently unknown. The objective of this paper is to characterise how preferences for medical interventions change throughout medical education and residency or fellowship training when confronted with scenarios of critical or terminal illness. METHODS: This is a single-centre cross-sectional study that enrolled medical students at Sidney Kimmel Medical College and residents and fellows at Thomas Jefferson University Hospital. Through an online survey we determined the preferences of medical trainees for specific interventions throughout medical training when presented with different clinical scenarios. Interventions were organised into three categories: standard, intermediate and aggressive. We analysed responses to questions regarding different scenarios in separate repeated measures logistic regression models. The probability of declining medical interventions was modelled, and significant predictors of refusal of interventions were identified. RESULTS: Years of training was a significant predictor of declining interventions for several scenarios. When faced with permanent physical disability, increased years of training led to a higher rate of refusal of intermediate (OR = 1.14 [1.02-1.28], p = 0.02) and aggressive interventions (OR = 1.15 [1.03-1.28], p = 0.01). For the scenario of terminal illness with associated physical disability, years of training significantly influenced refusal of intermediate (OR = 1.14 [1.04-1.26], p = 0.006) and aggressive (OR = 1.20 [1.08-1.34], p = 0.001) interventions. For the scenario of permanent cognitive impairment, increased years of training led to a higher rate of refusal of standard (OR = 1.14 [1.01-1.29], p = 0.03), intermediate (OR = 1.30 [1.13-1.50], p < 0.001) and aggressive (OR = 1.38 [1.14 1.66], p = 0.001) interventions. CONCLUSION: Changes in end-of-life preferences occur throughout medical training. Years of training influenced the likelihood of declining medical interventions when faced with scenarios of terminal illness and physical or cognitive disability. PMID- 26813001 TI - Is three a crowd? Impact of the presence of a medical student in the general practice consultation. AB - OBJECTIVES: To determine the impact of the presence of a medical student on the satisfaction and process of the general practice consultation from the perspective of the general practitioner (GP), patient and student. METHODS: An observational study was conducted in regional general practices accepting third year medical students. General practitioners, patients and medical students were asked to complete a questionnaire after each consultation. The main outcome measures were: patient satisfaction; GPs' perceived ability to deliver care; medical students' satisfaction with their learning experience; length of consultation; and patient waiting times. RESULTS: Of the 26 GP practices approached, 11 participated in the study (42.3%). Patients returned 477 questionnaires: 252 consultations with and 225 without a student present. Thirteen GPs completed 473 questionnaires: 248 consultations with and 225 without a student. Twelve students attended 255 consultations. Most patients (83.5%) were comfortable with the presence of a student. There were no significant differences between consultations with and without a student regarding the time the patients spent in the waiting room (p = 0.6), the patients' perspectives of how the GPs dealt with their presenting problems (100% versus 99.2%; p = 0.6) and overall satisfaction with the consultation (99.2% versus 99.1%; p = 0.5). Despite these reassuring findings, a significantly higher proportion of patients in consultations without students raised sensitive or personal issues (26.3% versus 12.6%; p < 0.001). There were no statistically significant differences in the lengths of consultations with and without students (81% versus 77% for 6-20 minutes consultation; p = 0.1) or in the GPs' perceptions of how they effectively managed the presenting problem (95.1% versus 96.0%; p = 0.4). Students found that the majority (83.9%) of the 255 consultations were satisfactory for learning. CONCLUSIONS: The presence of a medical student during the GP consultation was satisfactory for all participant groups. These findings support the ongoing and increased placement of medical students in regional general practice. Medical educators and GPs must recognise that patients may not raise personal issues with a student present. PMID- 26813002 TI - A multi-site study of strategies to teach critical thinking: 'why do you think that?'. AB - CONTEXT: Critical thinking (CT) is a fundamental skill for clinicians. It plays an essential role in clinical decision making, which has implications for diagnostic accuracy, appropriate management and, ultimately, patient outcomes. Many theoretical frameworks have conceptualised CT and its related constructs. Nevertheless, it is unclear how this topic is taught by faculty staff who teach health professionals. METHODS: The purpose of this multi-site qualitative study was to characterise the instructional strategies of faculty members actively teaching CT. We used semi-structured interviews to answer the following questions: (i) What approaches do faculty staff recognised by peers as good teachers in CT use to teach CT? (ii) How explicit is this teaching? We used snowball recruitment at eight participating institutions to identify faculty staff considered to be local experts in teaching CT. Forty-four eligible faculty members agreed to participate in semi-structured interviews, which were recorded and transcribed. We used the framework method to analyse the qualitative data. RESULTS: We organised the findings into themes of what faulty staff teach to learners (habits of mind, such as higher-order thinking and metacognition), how they teach (guiding principles of clinical relevance and perspective shifting, and concrete strategies such as questioning and group interaction) and why they teach CT (to produce the best possible health outcomes for patients). CONCLUSION: This work has practical recommendations for the individual faculty member. Promoting higher-level cognition, asking questions that probe the learner's understanding and linking discussions to the clinical context are some of the approaches that can be incorporated immediately. PMID- 26813003 TI - Using stroke thrombolysis to describe the role of repetition in learning a cognitive skill. AB - OBJECTIVE: To empirically describe how independent physicians develop a new cognitive clinical skill through repetition using the initiation of a stroke thrombolysis programme as a model. METHODS: This was a retrospective cohort study from April 2009 to March 2013. The setting was a single-centre, Canadian tertiary care community hospital. The participants were 52 physicians with no prior formal training in stroke thrombolysis assuming a new role of being front-line hyperacute stroke physicians. The main outcome measures were: time needed to accrue experience, door-to-needle time (DTN), with achievement of expertise defined as an average of <= 60 minutes, computed tomography (CT)-to-needle time (CTN), with achievement of expertise defined as an average of <= 35 minutes, usage of an outside expert stroke telemedicine service, and complication rates with intracranial haemorrhage (ICH). RESULTS: Seven hundred and fifteen cases of hyperacute stroke were seen over the 4-year study period. On average, a physician saw 0.025 cases per hour of code stroke coverage provided; only seven (13.5%) accrued more than 20 code stroke cases and only six (11.6%) ordered thrombolysis more than 10 times. By regression analysis, the average first DTN was 81.0 minutes (95% confidence interval [CI], 77.1-84.9 minutes) and incrementally improved linearly by 0.259 minutes per case seen (95% CI, 0.182-0.337 minutes per case). An estimated 71 cases needed to be seen for the average physician to achieve expertise. Results using CTN were highly similar. Overall, physicians used the external stroke telemedicine providers 23.2% of the time for their first five cases, a rate that decreased to about 5% by the 45th case. Over time, ICH rates were kept at expected benchmarks. CONCLUSIONS: Accruing sufficient experience of a new cognitive clinical skill can be challenging for independent physicians, with expertise gradually emerging in a largely linear fashion only after much repetition. PMID- 26813004 TI - The phantom professor: a medical student perspective. PMID- 26813005 TI - The phantom professor: an emeritus professor's perspective. PMID- 26813006 TI - Distinctive effects of CD34- and CD133-specific antibody-coated stents on re endothelialization and in-stent restenosis at the early phase of vascular injury. AB - It is not clear what effects of CD34- and CD133-specific antibody-coated stents have on re-endothelialization and in-stent restenosis (ISR) at the early phase of vascular injury. This study aims at determining the capabilities of different coatings on stents (e.g. gelatin, anti-CD133 and anti-CD34 antibodies) to promote adhesion and proliferation of endothelial progenitor cells (EPCs). The in vitro study revealed that the adhesion force enabled the EPCs coated on glass slides to withstand flow-induced shear stress, so that allowing for the growth of the cells on the slides for 48 h. The in vivo experiment using a rabbit model in which the coated stents with different substrates were implanted showed that anti-CD34 and anti-CD133 antibody-coated stents markedly reduced the intima area and restenosis than bare mental stents (BMS) and gelatin-coated stents. Compared with the anti CD34 antibody-coated stents, the time of cells adhesion was longer and earlier present in the anti-CD133 antibody-coated stents and anti-CD133 antibody-coated stents have superiority in re-endothelialization and inhibition of ISR. In conclusion, this study demonstrated that anti-CD133 antibody as a stent coating for capturing EPCs is better than anti-CD34 antibody in promoting endothelialization and reducing ISR. PMID- 26813007 TI - Epidemiological surveys of, and research on, soil-transmitted helminths in Southeast Asia: a systematic review. AB - Soil-transmitted helminth (STH) infections of humans fall within the World Health Organization's (WHO) grouping termed the neglected tropical diseases (NTDs). It is estimated that they affect approximately 1.4 billion people worldwide. A significant proportion of these infections are in the population of Southeast Asia. This review analyses published data on STH prevalence and intensity in Southeast Asia over the time period of 1900 to the present to describe age related patterns in these epidemiological measures. This is with a focus on the four major parasite species affecting humans; namely Ascaris lumbricoides, Trichuris trichiura and the hookworms; Necator americanus and Ancylostoma duodenale. Data were also collected on the diagnostic methods used in the published surveys and how the studies were designed to facilitate comparative analyses of recorded patterns and changes therein over time. PubMed, Google Scholar, EMBASE, ISI Web of Science, Cochrane Database of Systematic Reviews and the Global Atlas of Helminth Infections search engines were used to identify studies on STH in Southeast Asia with the search based on the major key words, and variants on, "soil-transmitted helminth" "Ascaris" "Trichuris" "hookworm" and the country name. A total of 280 studies satisfied the inclusion criteria from 11 Southeast Asian countries; Brunei, Cambodia, Indonesia, Lao People's Democratic Republic (Lao PDR), Malaysia, Myanmar, Philippines, Singapore, Thailand, Timor Leste and Vietnam. It was concluded that the epidemiological patterns of STH infection by age and species mix in Southeast Asia are similar to those reported in other parts of the world. In the published studies there were a large number of different diagnostic methods used with differing sensitivities and specificities, which makes comparison of the results both within and between countries difficult. There is a clear requirement to standardise the methods of both STH diagnosis in faecal material and how the intensity of infection is recorded and reported in future STH research and in monitoring and evaluation (M&E) of the impact of continuing and expanding mass drug administration (MDA) programmes. PMID- 26813009 TI - [Chronic issues related to traumatic brain injury: Traumatic brain injury is not an incident]. AB - Despite an increased awareness of the long-term consequences of traumatic brain injury, health care professionals often consider traumatic brain injury as an incident. However, patients with traumatic brain injury may experience long-term neurological, cognitive and behavioural problems. Due to the absence of valid prognostic models for long term sequelae there is a lack of standardized risk management. This is a major obstacle to placing traumatic brain injury in a chronic disease model and explains the difficulty in getting the correct support with the adequate level of expertise when required. Many patients face long-term unmet needs. By means of two case reports we discuss in more detail the long-term consequences of mild and severe traumatic brain injury. In addition, we discuss the organization of care for these patients in the Netherlands. In our opinion, the general practitioner has an important role in recognizing health care problems or neurobehavioural concerns for patients with traumatic brain injury. Subsequently, they can refer to, for example, the rehabilitation physician or neurologist, or draw attention to local patient associations. PMID- 26813008 TI - Plasminogen activator inhibitor-1 and type 2 diabetes: a systematic review and meta-analysis of observational studies. AB - An emerging body of evidence has implicated plasminogen activator inhibitor-1 (PAI-1) in the development of type 2 diabetes (T2D), though findings have not always been consistent. We systematically reviewed epidemiological studies examining the association of PAI-1 with T2D. EMBASE, PubMed, Web of Science, and the Cochrane Library were searched to identify studies for inclusion. Fifty-two studies (44 cross-sectional with 47 unique analytical comparisons and 8 prospective) were included. In pooled random-effects analyses of prospective studies, a comparison of the top third vs. bottom third of baseline PAI-1 values generated a RR of T2D of 1.67 (95% CI 1.28-2.18) with moderate heterogeneity (I(2) = 38%). Additionally, of 47 cross-sectional comparisons, 34(72%) reported significantly elevated PAI-1 among diabetes cases versus controls, 2(4%) reported significantly elevated PAI-1 among controls, and 11(24%) reported null effects. Results from pooled analyses of prospective studies did not differ substantially by study design, length of follow-up, adjustment for various putative confounding factors, or study quality, and were robust to sensitivity analyses. Findings from this systematic review of the available epidemiological literature support a link between PAI-1 and T2D, independent of established diabetes risk factors. Given the moderate size of the association and heterogeneity across studies, future prospective studies are warranted. PMID- 26813011 TI - [A neonatal supracondylar humeral fracture resembling a plexus injury]. AB - BACKGROUND: A supracondylar fracture of the distal humerus in the newborn is a rare injury that can occur during a traumatic partus. It can be difficult to make the correct diagnosis soon after birth. CASE DESCRIPTION: A neonate, born by a short fundal delivery in an otherwise minimally traumatic partus had reduced movement in the lower left arm on the first day of life. Physical examination and conventional radiography did not reveal any other abnormalities, suggesting a brachial plexus injury. As the arm movement did not improve, two weeks after birth radiographic investigations were repeated and a supracondylar humeral fracture was diagnosed. After a period of immobilisation without a plaster cast, the function of the elbow was completely restored in this otherwise healthy child. CONCLUSION: In neonates with a supracondylar humeral fracture clear clinical or radiological signs may be absent. According to the literature, ultrasonography is effective in revealing these fractures at an early stage. Generally, these fractures heal well without a plaster cast. PMID- 26813010 TI - [SSRIs for adolescents with medically unexplained symptoms]. AB - BACKGROUND: Medically unexplained symptoms (MUS) are somatic symptoms without a clear physical cause. MUS are highly prevalent amongst adolescents and result in overconsumption of healthcare and functional impairment. Current treatment options are limited and failing treatment results in high societal costs. CASE DESCRIPTION: We report the cases of two fifteen-year-old girls who were referred to us with an extensive history of MUS and affective symptoms resulting in general functional impairment and frequent visits to specialists. Previous treatments had been unsuccessful. Both adolescents were given selective serotonin reuptake inhibitor (SSRI) solution which resulted in impressive improvement of general functioning. At four to five months of follow-up these improvements had remained consistent. CONCLUSION: MUS can have extremely negative effects on adolescents, their support system and society. SSRIs may be a successful treatment option, but more research in adolescents is needed. PMID- 26813012 TI - [Anorectal pain in children: rare or rarely recognised?]. AB - Anorectal pain is a common symptom, often as part of functional gastrointestinal disorders. Children seldom present with this complaint. Proctalgia fugax and chronic proctalgia are both anorectal pain syndromes but differ in duration and frequency of episodes and in pain characteristics. No research has been conducted on anorectal pain syndromes in children. We present two patients. Firstly, an 8 year-old girl who suffered from anorectal cramps. We found no underlying cause apart from constipation. The symptoms disappeared spontaneously. The second concerned an 8-year-old boy who presented with recurrent anorectal cramps. He was diagnosed with celiac disease. Anorectal dysfunction and visceral hypersensitivity have been described in adult celiac patients. Symptoms of anorectal pain in children are rare probably because it often remains unrecognised. Noninvasive diagnostic methods and interventions are preferred in paediatric medicine. Screening for celiac disease in children with anorectal pain episodes should be considered. PMID- 26813013 TI - [The Warburg effect and its role in tumour metabolism: opportunities for new cancer treatments]. AB - Cancer cells are characterised by altered metabolism compared to healthy tissue. Ninety years ago, the German medical doctor and biochemist Otto Warburg discovered that tumours--when compared to healthy tissue--convert considerably more glucose into lactate, regardless of oxygen presence. This phenomenon is known as the Warburg effect; it is a hallmark of most cancer types and can be well understood by the process of somatic evolution. The Warburg effect explains the significance of the PET scan and may offer opportunities for new treatments of cancer. PMID- 26813014 TI - [The value of ipsilateral breast tumor recurrence as a quality indicator: hospital variation in the Netherlands]. AB - OBJECTIVE: All Dutch hospitals are obliged to report their 5-year ipsilateral breast tumor recurrence (IBTR) rate after breast cancer surgery. Experts decided that these rates should not exceed 5%. This study determined the value of IBTR as an indicator to compare quality of care between hospitals. DESIGN: Cohort study METHOD: All patients with breast cancer (pT1-3, any N, M0) who underwent surgery in 1 of 92 Dutch hospitals from 2003 to 2006 were identified in the Netherlands Cancer Registry. Data of recurrence was retrieved from hospital records. Five year IBTR rates for breast-conserving surgery (BCS) and mastectomy were calculated using the Kaplan-Meier method. Hospital variation was presented in funnel plots . Multivariate analysis was used to assess hospital characteristics associated with IBTR rates. RESULT: A total of 40,892 breast cancer patients were included. The overall 5-year IBTR rate was 2.85% (95%-CI 2.68-3.03) and was significantly lower for BCS than for mastectomy (2.38% vs 3.45%, p < 0.001). IBTR rates decreased over time in both groups. Rates varied between 0.77 and 5.70% between hospitals. When random variation is taken into account, only extremely high IBTR rates can be detected as deviant from the target value of 5%. Adjusting for tumor and patient characteristics, analyses showed that a higher volume of mastectomies is associated with lower IBTR rates. CONCLUSION: Our population based findings show that IBTR rates in the Netherlands are low and have improved over time. The 5-year IBTR rate as an indicator for quality of care of individual hospitals is of limited value. PMID- 26813015 TI - [Challenges in acute paediatric medicine]. AB - A big drop in the number of severe infections has resulted in less experience in recognising a seriously ill child. The challenge is finding a safe and effective balance between high-quality expertise and quickly accessible care, while avoiding over-diagnosis. There are a number of tools available to aid recognition of a seriously ill child and to avoid delay in diagnostic procedures and treatment: the use of a validated paediatric triage system, validated decision rules and guidelines, listening carefully to the parents ('my child's illness is different this time'), the clinical intuition of the experienced paediatrician and the provision of good 'safety net' advice to parents concerning the alarm signals and when they should contact a care provider. Experienced paediatricians should be at the forefront in the evaluation of the acutely ill child in order to teach their younger colleagues the importance of various alarm signals and the role played by clinical intuition. PMID- 26813016 TI - [Adolescents, MUPS and SSRIs: caution is advised]. AB - Although the prescription of SSRIs for patients with medically unexplained physical symptoms (MUPS) has increased in past years, there is still remarkably little evidence for their efficacy in adults with MUPS, as shown by a recent Cochrane review. As there is virtually no evidence that SSRIs are effective in adolescents with MUPS, doctors should think twice before prescribing SSRIs for this patient group; SSRIs can have serious side effects, particularly in adolescents. Increasing numbers of off-label prescriptions and a great improvement in symptoms in two adolescents with MUPS and psychiatric problems as described in a recent article in the Dutch Journal of Medicine (NTvG) do not justify the, albeit cautious, recommendation to consider prescribing SSRIs for adolescents with MUPS and depressive or anxiety symptoms. PMID- 26813018 TI - Effect of Oral Dimenhydrinate in Children with Acute Gastroenteritis: A Clinical Trial. AB - OBJECTIVES: One of the major causes of mortality in children is acute gastroenteritis. Vomiting is common in early stages of the disease. The aim of this study was to determine the effect of oral dimenhydrinate (DH) in the control of vomiting in cases of acute gastroenteritis in children. METHODS: This double blind, randomized, clinical trial was conducted in a university-affiliated hospital in a western province of Iran. Two hundred children aged one to 12 years old were randomly assigned to either drug or placebo groups. Children in the drug group received oral DH as four doses of 1 mg/kg every six hours (maximum 200 mg), and children in the placebo group received a placebo drug. The patients variables were compared 24 hours after receiving the first dose and at seven and 14 days after discharge. RESULTS: The mean number of episodes of vomiting was 4.4+/-2.5 in the drug group versus 4.4+/-2.1 in the placebo group, which was not statistically significant (p<0.050). The mean number of episodes of diarrhea was 7.4+/-3.2 and 10.1+/-2.8 in the drug and placebo groups, respectively, (p<0.050). The duration of diarrhea, side effects, need to revisit, and parent's satisfaction in both groups were also significantly different (p>0.050). CONCLUSIONS: Oral DH in children with acute gastroenteritis does not reduce the number and duration of vomiting. However, our results showed that consumption of DH in acute gastroenteritis patients was effective in reducing the frequency and duration of diarrhea and further investigation into this is warranted. PMID- 26813017 TI - Predictors of Post-Operative Pain Relief in Patients with Chronic Pancreatitis Undergoing the Frey or Whipple Procedure. AB - BACKGROUND: Post-operative pain relief in chronic pancreatitis (CP) is variable. Our objective was to determine clinical imaging or histopathologic predictor(s) of post-operative pain relief in CP patients undergoing the Whipple or Frey procedure. METHODS: All patients who underwent a Whipple (n = 30) or Frey procedure (n = 30) for painful CP between January 2003 and September 2013 were evaluated. A toxic etiology was defined as a history of alcohol use and/or smoking. The pre-operative abdominal CT was evaluated for calcification(s) and main pancreatic duct (MPD) dilation (>=5 mm). The post-operative histopathology was evaluated for severe fibrosis. Clinical imaging and histopathologic features were evaluated as predictors of post-operative pain relief using univariable and multivariable regression analysis. RESULTS: A total of 60 patients (age 51.6 years, 53% males) were included in our study, of whom 42 (70%) reported post operative pain relief over a mean follow-up of 1.1 years. There were 37 (62%) patients with toxic etiology, 36 (60%) each with calcification(s) and MPD dilation. A toxic etiology, calcifications, and severe fibrosis were associated with post-operative pain relief on univariable analysis (all p < 0.01). However, only a toxic etiology was an independent predictor of post-operative pain relief (OR 5.7, 95% CI 1.3, 24.5, p = 0.02). CONCLUSION: Only a toxic etiology, and not imaging or histopathologic findings, independently predicts post-operative pain relief in CP patients undergoing the Whipple or Frey procedure. PMID- 26813019 TI - Expression of Natural Cytotoxicity Receptors on and Intracellular Cytokine Production by NK Cells in Women with Gestational Diabetes Mellitus. AB - PROBLEM: To determine the role of peripheral blood NK (pNK) cells in putative etiology of gestational diabetes, the expression of surface markers on pNK cells and the percentage of cytokine-producing pNK cells in women at 12 weeks of pregnancy with gestational diabetes mellitus (GDM) were studied. METHOD OF STUDY: Multicolor flow cytometry was used to analyze the expression of NK cell surface receptors (CD16, NKp46, and NKp30) and intracellular cytokines (IFN-gamma, TNF alpha, TGF-beta, and VEGF) in pNK cells (CD56(dim) and CD56(bright) ) at 12 weeks of pregnancy with GDM (n = 7) and non-GDM (n = 28). RESULTS: CD56(bright) /CD16( ) NK and CD56(bright) /NKp46(+) NK cell percentage were significantly lower in GDM women than that in non-GDM women. IFN-gamma- and TNF-alpha-producing CD56(+) cells, respectively, were significantly high, while TGF-beta- and VEGF-producing CD56(+) cells and CD56(bright) cells, respectively, were significantly low in GDM women. CONCLUSIONS: Women with GDM possibly have abnormal NK cell function for the expression of surface receptors and cytokine production. PMID- 26813020 TI - Retraction: "Isolation, characterization, and effect of administration in vivo, a novel probiotic strain from pig feces" by Yasuhiro Ihara, Hideki Hyodo, Shin Sukegawa, Hiroshi Murakami and Fumiki Morimatsu. PMID- 26813021 TI - Supernatant protein biomarkers of red blood cell storage hemolysis as determined through an absolute quantification proteomics technology. AB - BACKGROUND: Laboratory technologies have highlighted the progressive accumulation of the so-called "storage lesion," a wide series of alterations to stored red blood cells (RBCs) that may affect the safety and effectiveness of the transfusion therapy. New improvements in the field are awaited to ameliorate this lesion, such as the introduction of washing technologies in the cell processing pipeline. Laboratory studies that have tested such technologies so far rely on observational qualitative or semiquantitative techniques. STUDY DESIGN AND METHODS: A state-of-the-art quantitative proteomics approach utilizing quantitative concatamers (QconCAT) was used to simultaneously monitor fluctuations in the abundance of 114 proteins in AS-3 RBC supernatants (n = 5; 11 time points, including before and after leukoreduction, at 3 hours, on Days 1 and 2, and weekly sampling from Day 7 through Day 42). RESULTS: Leukoreduction dependent depletion of plasma proteins was observed at the earliest time points. A subset of proteins showed very high linear correlation (r(2) > 0.9) not only with storage time, but also with absolute levels of hemoglobin alpha1 and beta, a proxy for RBC hemolysis and vesiculation. Linear regression was performed to describe the temporal relationship between these proteins. Our findings suggest a role for supernatant glyceraldehyde-3-phosphate dehydrogenase; peroxiredoxin-1, 2, and -6; carbonic anhydrase-1 and -2; selenium binding protein-1; biliverdin reductase; aminolevulinate dehydratase; and catalase as potential biomarkers of RBC quality during storage. CONCLUSION: A targeted proteomics technology revealed novel biomarkers of the RBC storage lesion and promises to become a key analytical readout for the development and testing of alternative cell processing strategies. PMID- 26813022 TI - Rich diversity and potency of skin antioxidant peptides revealed a novel molecular basis for high-altitude adaptation of amphibians. AB - Elucidating the mechanisms of high-altitude adaptation is an important research area in modern biology. To date, however, knowledge has been limited to the genetic mechanisms of adaptation to the lower oxygen and temperature levels prevalent at high altitudes, with adaptation to UV radiation largely neglected. Furthermore, few proteomic or peptidomic analyses of these factors have been performed. In this study, the molecular adaptation of high-altitude Odorrana andersonii and cavernicolous O. wuchuanensis to elevated UV radiation was investigated. Compared with O. wuchuanensis, O. andersonii exhibited greater diversity and free radical scavenging potentiality of skin antioxidant peptides to cope with UV radiation. This implied that O. andersonii evolved a much more complicated and powerful skin antioxidant peptide system to survive high-altitude UV levels. Our results provided valuable peptidomic clues for understanding the novel molecular basis for adaptation to high elevation habitats. PMID- 26813023 TI - The pathogenesis of necrotic enteritis in chickens: what we know and what we need to know: a review. AB - This review summarizes advances in understanding the pathogenesis of necrotic enteritis of chickens caused by netB-positive Clostridium perfringens. The discovery of NetB as the essential toxin trigger for the disease was followed by recognition that it forms part of a large plasmid-encoded 42 kb pathogenicity locus (NELoc-1). While the locus is critical for toxin production, it likely has additional functions related to colonization and degradation of the mucus barrier, which are essential both to multiplication and to bringing NetB close to the intestinal epithelium. Two "chitinases" (glycoside hydrolases (GHs)) present on NELoc-1 are predicted to be involved in mucin degradation, as is the large carbohydrate-binding metalloprotease, shown to be involved in mucinase activity in other clostridia. A second pathogenicity locus found in netB-positive C. perfringens, NELoc-2, also encodes a GH likely involved in mucin degradation. Upon reaching a sufficient cell density on the intestinal mucosa, the Agr-like quorum-sensing system is triggered, which in turn up-regulates the VirR/VirS regulon. This regulon includes NetB. Where NetB initiates damage is unresolved, but it may be deep in the intestinal mucosa, rather than superficially. As the disease progresses, C. perfringens line what remains of the intestinal epithelium in large numbers. This likely involves a number of different bacterial adhesins, including additional NELoc-1-encoded bacterial surface proteins, some of which may adhere to epithelial cell ligands exposed by bacterial sialidases. Further studies of the pathogenesis of necrotic enteritis should lead to development of novel ways to control the infection. PMID- 26813024 TI - Detection of Protein Glycosylation Using Tip-Enhanced Raman Scattering. AB - The correct glycosylation of biopharmaceutical glycoproteins and their formulations is essential for them to have the desired therapeutic effect on the patient. It has recently been shown that Raman spectroscopy can be used to quantify the proportion of glycosylated protein from mixtures of native and glycosylated forms of bovine pancreatic ribonuclease (RNase). Here we show the first steps toward not only the detection of glycosylation status but the characterization of glycans themselves from just a few protein molecules at a time using tip-enhanced Raman scattering (TERS). While this technique generates complex data that are very dependent on the protein orientation, with the careful development of combined data preprocessing, univariate and multivariate analysis techniques, we have shown that we can distinguish between the native and glycosylated forms of RNase. Many glycoproteins contain populations of subtly different glycoforms; therefore, with stricter orientation control, we believe this has the potential to lead to further glycan characterization using TERS, which would have use in biopharmaceutical synthesis and formulation research. PMID- 26813025 TI - Experimental reproduction of necrotic enteritis in chickens: a review. AB - This review discusses key factors important in successful experimental reproduction of necrotic enteritis (NE) in chickens, and how these factors can be adjusted to affect the severity of the lesions induced. The critical bacterial factor is the need to use virulent, netB-positive, strains of Clostridium perfringens; disease severity can be enhanced by using netB-positive C. perfringens strains that are also tpeL-positive, by the use of young rather than old broth cultures, and by the number of days of inoculation and the number of bacteria used. Use of cereals rich in non-starch polysaccharides can enhance disease, as does use of animal proteins. Administration of coccidia, including coccidial vaccines, combined with netB-positive C. perfringens, increases the severity of experimentally-induced NE. Dietary manipulation may be less important in coccidia-based models since the latter are so effective. Disease scoring systems and welfare considerations are discussed. PMID- 26813026 TI - Gas Evolution in LiNi0.5Mn1.5O4/Graphite Cells Studied In Operando by a Combination of Differential Electrochemical Mass Spectrometry, Neutron Imaging, and Pressure Measurements. AB - The cycling performance and in operando gas analysis of LiNi0.5Mn1.5O4 (LNMO)/graphite cells with reasonably high loading, containing a "standard" carbonate-based electrolyte is reported. The gas evolution over the first couple of cycles was thoroughly investigated via differential electrochemical mass spectrometry (DEMS), neutron imaging and pressure measurements. The main oxidation and reduction products were identified as CO2, H2 and C2H4. In different sets of experiments graphite was substituted with delithiated LiFePO4 (LFP) and LNMO with LFP to distinguish between processes occurring at either anode or cathode and gain mechanistic insights. Both C2H4 and H2 were found to be mainly formed at the anode side, while CO2 is generated at the cathode. The results from DEMS analysis further suggest that the Ni redox couples play a profound role in the evolution of CO2 at the LNMO/electrolyte interface. Lastly, it is shown that the cycling stability and capacity retention of LNMO/graphite cells can be considerably improved by a simple cell formation procedure. PMID- 26813027 TI - Yamadazyma kitorensis f.a., sp. nov. and Zygoascus biomembranicola f.a., sp. nov., novel yeasts from the stone chamber interior of the Kitora tumulus, and five novel combinations in Yamadazyma and Zygoascus for species of Candida. AB - Analysis of D1/D2 large-subunit (LSU) rRNA gene sequences predicted that 17 yeast isolates, mainly from viscous gels (biofilms) taken from the stone chamber interior of the Kitora tumulus in Nara, Japan, were placed in the Yamadazyma and Zygoascus clades. Polyphasic characterization, including morphological, physiological and chemotaxonomic characteristics, multigene sequence divergence and DNA-DNA hybridization, strongly suggested the assignment of one novel species to each of the clades; these are Yamadazyma kitorensis f.a., sp. nov., with the type strain JCM 31005T (ex-type CBS 14158T=isolate K8617-6-8T), and Zygoascus biomembranicola f.a., sp. nov., with the type strain JCM 31007T (ex-type CBS 14157T=isolate K61208-2-11T). Furthermore, the transfer of five known species of the genus Candida as novel combinations to the genera Yamadazyma and Zygoascus is proposed; these are Yamadazyma olivae f.a., comb. nov. (type strain CBS 11171T=ATCC MYA-4568T), Yamadazyma tumulicola f.a., comb. nov. (type strain JCM 15403T=ex-type CBS 10917T=isolate T6517-9-5T), Yamadazyma takamatsuzukensis f.a., comb. nov. (type strain JCM 15410T=CBS 10916T = isolate T4922-1-1T), Zygoascus polysorbophila f.a., comb. nov. (type strain NRRL Y-27161T=CBS 7317T) and Zygoascus bituminiphila f.a., comb. nov. (type strain CBS 8813T=MUCL 41424T). PMID- 26813029 TI - Improvements in life expectancy among Australians due to reductions in smoking: Results from a risk percentiles approach. AB - BACKGROUND: Tobacco smoking is a major burden on the Australian population in terms of health, social and economic costs. Because of this, in 2008, all Australian Governments agreed to set targets to reduce prevalence of smoking to 10 % by 2018 and subsequently introduced several very strong anti-smoking measures. On this backdrop, we estimated in 2012-13 the impact of several scenarios related to reduction of smoking prevalence to 10 % across the entire Australian population and for below specific ages, on improving life expectancy. METHODS: Using the risk percentiles method the Australian Diabetes, Obesity and Lifestyle (AUSDIAB) baseline survey and the Australian Bureau of Statistics (ABS) age-sex specific death counts were analyzed. RESULTS: Amongst men the gains in life expectancy associated with 10 % smoking prevalence are generally greater than those of women with average life expectancy for men increasing by 0.11 to 0.41 years, and for women by 0.12 to 0.29 years. These are at best 54 % and 49 % for men and women of the gains achieved by complete smoking cessation. The gains plateau for interventions targeting those <70 and <80 years. Amongst smokers the potential gains are much greater, with an increase in average life expectancy amongst men smokers of 0.43 to 2.08 years, and 0.73 to 2.05 years amongst women smokers. These are at best 46 % and 38 % for men and women smokers of the gains achieved by complete smoking cessation. CONCLUSION: The estimated optimum gain in life expectancy is consistent with potentially moderate gains which occur when both men and women below 60 years are targeted to reduce smoking prevalence to 10 %. PMID- 26813028 TI - Insights into Complex Oxidation during BE-7585A Biosynthesis: Structural Determination and Analysis of the Polyketide Monooxygenase BexE. AB - Cores of aromatic polyketides are essential for their biological activities. Most type II polyketide synthases (PKSs) biosynthesize these core structures involving the minimal PKS, a PKS-associated ketoreductase (KR) and aromatases/cyclases (ARO/CYCs). Oxygenases (OXYs) are rarely involved. BE-7585A is an anticancer polyketide with an angucyclic core. (13)C isotope labeling experiments suggest that its angucyclic core may arise from an oxidative rearrangement of a linear anthracyclinone. Here, we present the crystal structure and functional analysis of BexE, the oxygenase proposed to catalyze this key oxidative rearrangement step that generates the angucyclinone framework. Biochemical assays using various linear anthracyclinone model compounds combined with docking simulations narrowed down the substrate of BexE to be an immediate precursor of aklaviketone, possibly 12-deoxy-aklaviketone. The structural analysis, docking simulations, and biochemical assays provide insights into the role of BexE in BE-7585A biosynthesis and lay the groundwork for engineering such framework-modifying enzymes in type II PKSs. PMID- 26813030 TI - Complementary and alternative medicine practitioner use prior to pregnancy predicts use during pregnancy. AB - The objective of the authors in this study was to determine if prior visits to a complementary and alternative medicine (CAM) practitioner were associated with CAM use during pregnancy. The study sample comprised the Australian Longitudinal Study on Women's Health. Women were surveyed prior to pregnancy in 2006, and then again in 2010 if they were pregnant or had recently given birth, and asked a range of questions relating to demographic variables, health status, and use of CAM. A multivariable analysis identified significant covariates associated with visits to specific CAM practitioner modalities during pregnancy. Of the 447 women who consulted a CAM practitioner prior to pregnancy, 62.4% (n = 279) continued this use during pregnancy. Prior use of massage therapy, acupuncture, herbalist/naturopath, or chiropractor was related to use of the same service during pregnancy. Higher income and working full-time were associated with the continued use of massage, while continued visits to a chiropractor were associated with having depressive symptoms, a urinary tract infection, and living in a rural community. Prior use of CAM was highly related to continuing use during pregnancy. Further research is required to elucidate the benefits women attain from a CAM-model of care that they do not get from their conventional maternity care providers alone. PMID- 26813031 TI - Surgical treatment of Peyronie's disease by modified 16-dot placation in China. AB - OBJECTIVE: To assess the long-term patient's satisfaction and functional results of surgical correction for Peyronie's disease (PD) patients with penile curvature by 16-dot minimal tension placation and its modification in Chinese population. PATIENTS AND METHODS: Between August 2004 and December 2008, 32 patients with PD underwent surgical correction of penile curvature by 16-dot minimal tension placation and its modification. Indications for operation included PD patients with penile curvature, adequate erectile capacity, difficulty or inability to vaginal penetration. Preoperative evaluation included International Index of Erectile Function 5 (IIEF-5) questionnaire score, pain on erection and physical examination. Patients were recommended daily low dose phosphodiesterase type 5 (PDE5) inhibitors two weeks after surgery and maintained for two months. At follow-up, patients and partner's satisfaction and erectile function were assessed by IIEF-5 questionnaire score. RESULTS: There were no surgery-related complications, and 94% of patients and 88% of partners reported overall satisfaction after the surgery. Complete penile straightening was achieved in 27 (84%) patients. Slight residual curvatures were observed in 4 patients, which did not affect their sexual intercourse. All patients were satisfied with postoperative penile length while shortening of the penis was noted in 13 patients ?(40%) with median penile length loss of 1.5 cm. In addition, no de novo erectile dysfunction was observed, and sexual function was significantly improved evidenced by the IIEF-5 scores, especially in the patients who have received PDE5 inhibitors for two months after two weeks surgery. CONCLUSIONS: Correction of penile curvature using 16-dot placation and its modification is a simple and safe method to achieve cosmetic and functional satisfaction in carefully selected PD patients. PMID- 26813033 TI - Positive Psychotherapy to Improve Autonomic Function and Mood in ICD Patients (PAM-ICD): Rationale and Design of an RCT Currently Underway. AB - BACKGROUND: Improving mental and physical health of patients with implantable cardioverter defibrillators (ICD) is critical because this group is at high risk for ventricular arrhythmias and sudden death and depressed or anxious cardiovascular disease (CVD) patients appear to be at even higher risk for mortality compared to nondepressed or nonanxious CVD patients. Further, autonomic dysfunction is present in these patients, and negative emotions and arrhythmias form a downward spiral further worsening mood, well-being, and cardiovascular health. Much research demonstrates that positive emotion is related to health benefits, improved physiology, and increased survival. METHODS AND RESULTS: This is a two-arm randomized controlled trial aiming to recruit 60 adult ICD patients comparing 12 individually delivered, weekly sessions of: (1) a positive emotion focused cognitive-behavioral therapy (Quality of Life Therapy [QOLT]), and (2) Heart Healthy Education. Autonomic functioning, heart rhythm indices, and psychosocial health are measured at baseline, 3 months, and 9 months. The first goal is feasibility and acceptability, with the primary outcome being arrhythmic event frequency data. CONCLUSION: This study is designed to test whether QOLT produces changes in mood, quality of life/well-being, autonomic function, and arrhythmic and ICD therapy event rates. This feasibility trial is a foundational step for the next trial of QOLT to help determine whether a 3-month QOLT trial can reduce arrhythmias occurrences among ICD patients, and examine a mechanism of autonomic functioning. This study may help to develop and implement new medical or psychological therapies for ICD patients. PMID- 26813034 TI - Standard cystectomy fits all: truth or myth? AB - Radical cystectomy (RC) with pelvic lymph node dissection (PLND) followed by urinary diversion is the treatment of choice for muscle-invasive bladder cancer (BC) and non-invasive BC refractory to transurethral resection of the bladder (TUR-B) and/or intravesical instillation therapies. Since the morbidity and possible mortality of this surgery are relevant, care must be taken in the preoperative selection of patients for the various organ-sparing procedures (e.g., bladder-sparing, nerve sparing, seminal vesicle sparing) and various types of urinary diversion. The patient's performance status and comorbidities, along with individual tumor characteristics, determine possible surgical steps during RC. This individualized approach to RC in each patient can maximize oncological safety and minimize avoidable side effects, rendering 'standard' cystectomy a surgery of the past. PMID- 26813036 TI - The OPTN Deceased Donor Potential Study: Implications for Policy and Practice. AB - The Organ Procurement and Transplantation Network (OPTN) Deceased Donor Potential Study, funded by the Health Resources and Services Administration, characterized the current pool of potential deceased donors and estimated changes through 2020. The goal was to inform policy development and suggest practice changes designed to increase the number of donors and organ transplants. Donor estimates used filtering methodologies applied to datasets from the OPTN, the National Center for Health Statistics, and the Agency for Healthcare Research and Quality and used these estimates with the number of actual donors to estimate the potential donor pool through 2020. Projected growth of the donor pool was 0.5% per year through 2020. Potential donor estimates suggested unrealized donor potential across all demographic groups, with the most significant unrealized potential (70%) in the 50-75-year-old age group and potential Donation after Circulatory Death (DCD) donors. Actual transplants that may be realized from potential donors in these categories are constrained by confounding medical comorbidities not identified in administrative databases and by limiting utilization practices for organs from DCD donors. Policy, regulatory, and practice changes encouraging organ procurement and transplantation of a broader population of potential donors may be required to increase transplant numbers in the United States. PMID- 26813032 TI - Microglia in the spinal cord and neuropathic pain. AB - In contrast to physiological pain, pathological pain is not dependent on the presence of tissue-damaging stimuli. One type of pathological pain - neuropathic pain - is often a consequence of nerve injury or of diseases such as diabetes. Neuropathic pain can be agonizing, can persist over long periods and is often resistant to known painkillers. A growing body of evidence shows that many pathological processes within the central nervous system are mediated by complex interactions between neurons and glial cells. In the case of painful peripheral neuropathy, spinal microglia react and undergo a series of changes that directly influence the establishment of neuropathic pain states. After nerve damage, purinergic P2X4 receptors (non-selective cation channels activated by extracellular adenosine triphosphate) are upregulated in spinal microglia in a manner that depends on the transcription factors interferon regulatory factor 8 and 5, both of which are expressed in microglia after peripheral nerve injury. P2X4 receptor expression on the cell surface of microglia is also regulated at the post-translational level by signaling from CC chemokine receptor chemotactic cytokine receptor 2. Furthermore, spinal microglia in response to extracellular stimuli results in signal transduction through intracellular signaling cascades, such as mitogen-activated protein kinases, p38 and extracellular signal-regulated protein kinase. Importantly, inhibiting the function or expression of these microglial molecules suppresses the aberrant excitability of dorsal horn neurons and neuropathic pain. These findings show that spinal microglia are a central player in mechanisms for neuropathic pain, and might be a potential target for treating the chronic pain state. PMID- 26813037 TI - Differentiation of Cardiac from Noncardiac Pleural Effusions in Cats using Second Generation Quantitative and Point-of-Care NT-proBNP Measurements. AB - BACKGROUND: Pleural effusion is a common cause of dyspnea in cats. N-terminal pro B-type natriuretic peptide (NT-proBNP) measurement, using a first-generation quantitative ELISA, in plasma and pleural fluid differentiates cardiac from noncardiac causes of pleural effusion. HYPOTHESIS/OBJECTIVES: To determine whether NT-proBNP measurements using second-generation quantitative ELISA and point-of-care (POC) tests in plasma and pleural fluid distinguish cardiac from noncardiac pleural effusions and how results compare to the first-generation ELISA. ANIMALS: Thirty-eight cats (US cohort) and 40 cats (UK cohort) presenting with cardiogenic or noncardiogenic pleural effusion. METHODS: Prospective cohort study. Twenty-one and 17 cats in the US cohort, and 22 and 18 cats in the UK cohort were classified as having cardiac or noncardiac pleural effusion, respectively. NT-proBNP concentrations in paired plasma and pleural fluid samples were measured using second-generation ELISA and POC assays. RESULTS: The second generation ELISA differentiated cardiac from noncardiac pleural effusion with good diagnostic accuracy (plasma: sensitivity, 95.2%, specificity, 82.4%; pleural fluid: sensitivity, 100%, specificity, 76.5%). NT-proBNP concentrations were greater in pleural fluid (719 pmol/L (134-1500)) than plasma (678 pmol/L (61 1500), P = 0.003), resulting in different cut-off values depending on the sample type. The POC test had good sensitivity (95.2%) and specificity (87.5%) when using plasma samples. In pleural fluid samples, the POC test had good sensitivity (100%) but low specificity (64.7%). Diagnostic accuracy was similar between first and second-generation ELISA assays. CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of NT-proBNP using a quantitative ELISA in plasma and pleural fluid or POC test in plasma, but not pleural fluid, distinguishes cardiac from noncardiac causes of pleural effusion in cats. PMID- 26813038 TI - Public Health Nurses' Activities for Suicide Prevention in Japan. AB - OBJECTIVE: Suicide is a major health issue worldwide, including in Japan. Japanese public health nurses (PHNs) play a distinctive role in suicide prevention, although few studies have delineated this role. The purpose of this study was to develop a conceptual framework that elucidates PHNs' activities for suicide prevention. DESIGN AND SAMPLE: Semi-structured interviews were conducted in 2012-2013 with 15 PHNs who worked in Tokyo metropolitan regions. Data were analyzed qualitatively using grounded theory, and a conceptual framework with seven categories was developed. RESULTS: Three phases that depict the PHNs' suicide prevention activities emerged. Phase I, Pursuing to understand suicide cases, included two categories: tracing back individual suicide cases and raising consciousness among the general public. Phase II, Spreading a web of care, included three categories: knitting a caring network, weaving regular programs into the web, and continuing to be a member of the web. Phase III, Maintaining motivation and commitment, included two categories: legitimatizing suicide prevention and cultivating continued commitment in the community. CONCLUSION: The activities of suicide prevention by PHNs included a process of developing a caring network that lead to the enhancement of the caring capacity of the community as a whole. PMID- 26813040 TI - Erratum. PMID- 26813039 TI - Atrasentan increased the expression of klotho by mediating miR-199b-5p and prevented renal tubular injury in diabetic nephropathy. AB - Atrasentan is a promising therapy for treating diabetic nephropathy (DN). Here we evaluated whether atrasentan down-regulated the miR-199b-5p expression, thereby increasing klotho and preventing renal tubular injury in DN. One-hundred patients with type 2 diabetes mellitus (T2DM) and 40 healthy subjects were included. A DN mice model was established by an injection of streptozotocin (STZ). Human renal proximal tubular epithelial HK-2 cells were exposed to high glucose (20 mmol/L). Treated the mice and HK-2 cells with atrasentan, and we then investigated whether and how miR-199b-5p and Klotho were involved in preventing renal tubular injury in DN. In patients, the serum miR-199b-5p level increased and the klotho concentration decreased in accordance with elevated albuminuria. Atrasentan down regulated miR-199b-5p and up-regulated klotho of the DN mice and HK-2 cells exposed to high glucose. High glucose promoted the binding of histone H3 to the miR-199b-5p promoter, and atrasentan canceled this effect. MiR-199b-5p targeted the 3' UTR of klotho. Overexpression of miR-199b-5p canceled the effects of atrasentan on klotho expression and apoptosis of renal tubular cells in both in vivo and in vitro. The increased serum klotho, mediated by miR-199b-5p, is a possible mechanism by which atrasentan prevents renal tubular injury in DN. PMID- 26813042 TI - CT and radiation dose: Where are we now? PMID- 26813043 TI - Should children travel overseas for proton therapy? PMID- 26813041 TI - Mosaic analysis of cell rearrangements during ureteric bud branching in dissociated/reaggregated kidney cultures and in vivo. AB - BACKGROUND: Cell rearrangements mediated by GDNF/Ret signaling underlie the formation of the ureteric bud (UB) tip domain during kidney development. Whether FGF signaling also influences these rearrangements is unknown. Chimeric embryos are a powerful tool for examining the genetic controls of cellular behaviors, but generating chimeras by traditional methods is expensive and laborious. Dissociated fetal kidney cells can reorganize to form complex structures including branching UB tubules, providing an easier method to generate renal chimeras. RESULTS: Cell behaviors in normal or chimeric kidney cultures were investigated using time-lapse imaging. In Spry1(-/-) <-> wild-type chimeras, cells lacking Spry1 (a negative regulator of Ret and FGF receptor signaling) preferentially occupied the UB tips, as previously observed in traditional chimeras, thus validating this experimental system. In Fgfr2(UB-/-) <-> wild-type chimeras, the wild-type cells preferentially occupied the tips. Independent evidence for a role of Fgfr2 in UB tip formation was obtained using Mosaic mutant Analysis with Spatial and Temporal control of Recombination (MASTR). CONCLUSIONS: Dissociation and reaggregation of fetal kidney cells of different genotypes, with suitable fluorescent markers, provides an efficient way to analyze cell behaviors in chimeric cultures. FGF/Fgfr2 signaling promotes UB cell rearrangements that form the tip domain, similarly to GDNF/Ret signaling. PMID- 26813044 TI - Inter- and intra-fraction motion in stereotactic body radiotherapy for spinal and paraspinal tumours using cone-beam CT and positional correction in six degrees of freedom. AB - INTRODUCTION: Stereotactic body radiotherapy (SBRT) for spinal tumours delivers high doses per fraction to targets in close proximity to neural tissue. With steep dose gradients, small changes in position can confer significant dosimetric impact on adjacent structures. We analysed positioning error in consecutively treated patients on a strict image-guidance protocol with online correction in 6 degrees of freedom (6-DOF). METHODS: Set-up error, residual error post-correction and intra-fraction motion for 30 courses of spinal SBRT in 27 patients were assessed using cone-beam CT. Positional error was corrected in x, y and z translational planes and rotational axes using a robotic couch, applying 2 mm and 2 degrees action levels. Linear mixed-effects model assessed whether positional error was influenced by factors such as vertebral level, immobilisation device and treatment duration. RESULTS: Sixty-two fractions were delivered with 225 image registrations. Median treatment duration was significantly longer for patients treated with static-field intensity-modulated radiotherapy compared with volumetric-modulated arc treatment--40 min versus 28 min, respectively (P = 0.01). Across all fractions, the median residual positional error after initial correction was greatest in the x translational plane (0.5 mm; 95% confidence interval (CI) 0.3-0.6) and y rotational axis (0.25 degrees ; 95% CI 0.1-0.3). Median intra-fraction error was also greatest in the x-plane (0.7 mm; 95% CI 0.5 1.0) and y-axis (0.4 degrees ; 95% CI 0.2-0.5). CONCLUSION: With strict immobilisation, image-guidance and 6-DOF correction, our current practice of applying 3-mm planning margins for target volumes and critical structures appears safe. Lower image-guidance action thresholds plus verification with end-to-end testing would be recommended before further reducing margins. PMID- 26813046 TI - Development and validation of hydrophobic molecular fields derived from the quantum mechanical IEF/PCM-MST solvation models in 3D-QSAR. AB - Since the development of structure-activity relationships about 50 years ago, 3D QSAR methods belong to the most refined ligand-based in silico techniques for prediction of biological data using physicochemical molecular fields. In this scenario, this study reports the development and validation of quantum mechanical (QM)-based hydrophobic descriptors derived from the parametrized MST continuum solvation model to be used in 3D-QSAR studies within the framework of the Hydrophobic Pharmacophore (HyPhar) method. To this end, five sets of compounds reported in the literature (dopamine D2/D4 antagonists, antifungal 2-aryl-4 chromanones, and inhibitors of GSK-3, cruzain and thermolysin) have been revisited. The results derived from the QM/MST-based hydrophobic descriptors have been compared with previous CoMFA and CoMSIA studies, and examined in light of the available X-ray crystallographic structures of the targets. The analysis reveals that the combination of electrostatic and nonelectrostatic components of the octanol/water partition coefficient yields pharmacophoric models fully comparable with the predictive potential of standard 3D-QSAR techniques. Moreover, the graphical representation of the hydrophobic maps provides a direct linkage with the pattern of interactions found in crystallographic structures. Overall, the introduction of the QM/MST-based descriptors, which could be easily adapted to other continuum solvation formalisms, paves the way to novel computational strategies for disclosing structure-activity relationships in drug design. (c) 2016 Wiley Periodicals, Inc. PMID- 26813047 TI - Relevance of a 5-grass sublingual tablet for immunotherapy of patients with grass pollen allergy in North America. AB - Grass pollen allergy is common and clinically consequential in North America. While it is frequently treated with subcutaneous or sublingual immunotherapy, debate remains regarding whether allergen immunotherapy is best carried out using a single representative or multiple cross-reactive allergen(s). Patients are commonly exposed to pollens from multiple allergenic grass species belonging to the Pooideae subfamily. Beyond the known IgE cross-reactivity, considerable molecular heterogeneity exists with respect to allergen content among grass species, with further evidence that these molecular variants can be detected by the patients' immune system. These observations provide a compelling scientific rationale for the use of mixed pollen allergen extracts to broaden the allergen repertoire, with the aim of reorienting inappropriate immune responses in allergic patients. PMID- 26813049 TI - Role of priority setting in implementing universal health coverage. PMID- 26813048 TI - Enhanced CO2 Resistance for Robust Oxygen Separation Through Tantalum-doped Perovskite Membranes. AB - Oxygen selective membranes with enhanced oxygen permeability and CO2 resistance are highly required in sustainable clean energy generation technologies. Here, we present novel, cobalt-free, SrFe1-x Tax O3-delta (x=0, 0.025, 0.05, 0.1, 0.2) perovskite membranes. Ta-doping induced lattice structure progression from orthorhombic (x=0) to cubic (x=0.05). SrFe0.95 Ta0.05 O3-delta (SFT0.05) showed the highest oxygen flux rates reaching 0.85 mL min(-1) cm(-2) at 950 degrees C on a 1.0 mm-thick membrane. Surface decoration can increase the permeation rate further. Ta inclusion within the perovskite lattice of SrFeO3-delta (SF) enhanced the CO2 resistance of the membranes significantly as evidenced by the absence of the carbonate functional groups on the FTIR spectrum when exposed to CO2 atmosphere at 850 degrees C. The CO2 resistance of Ta-doped SF compounds correlates with the lower basicity and the higher binding energy for the lattice oxygen. SFT0.05 demonstrated high stability during long-term permeation tests under 10% CO2 atmosphere. PMID- 26813050 TI - Pet Therapy: Enhancing Social and Cardiovascular Wellness in Community Dwelling Older Adults. AB - Pet therapy can be therapeutic for older adults living in the community. A crossover design was used to examine changes in blood pressure and heart rate before and after a pet therapy visit versus a volunteer-only visit in 28 community dwelling older adults. Relationships among stress, pet attitude, social support, and health status were also examined. Study findings supported that pet therapy significantly decreased blood pressure and heart rate. Ultimately, the findings supported the notion that community health nurses should consider developing and implementing pet therapy programs in the communities they serve. Further implications for community health nurses are discussed. PMID- 26813051 TI - Life Skills Interventions to Improve Social Confidence, Self-Management, and Protection against Drug Use in Rural Elementary School Aged Children. AB - This pilot project evaluated the effectiveness of a life skills training program for elementary-school-aged children for development of social confidence, self management, and general social and drug resistance skills. The setting was a rural community after-school program. Children participated in 30-min weekly sessions for 8 weeks. Pre- and posttest scores were analyzed to determine effectiveness of the program. Results showed improvements in antismoking and antidrinking attitudes and use of self-management and general social skills, and social confidence in conflict situations. The life skills training intervention serves as a potential supplement to community programs for the prevention of behaviors such as bullying, smoking and drug use among elementary school aged children. PMID- 26813053 TI - Assessment of Barriers to Screening Mammograms for Rural, Poor, Uninsured Women and a Community Plan of Action. AB - This project determined the barriers to obtaining screening mammograms for women aged 40-64 years in rural northwest Georgia, sampling 20 poor and uninsured women and 5 key community professionals. Data were collected from the women participants regarding mammogram screening beliefs about their susceptibility, barriers encountered, and benefits identified. The same women and key community providers were interviewed about their perception of barriers to receiving mammograms. The women experienced more barriers and believed that they had a greater susceptibility to developing breast cancer compared to previous research. The most overwhelming barrier was cost. A community plan was developed to address screening needs. PMID- 26813054 TI - Increasing Cervical Cancer and Human Papillomavirus Prevention Knowledge and HPV Vaccine Uptake through Mother/Daughter Education. AB - This evidence-based initiative assessed the impact of language-appropriate cervical cancer and human papillomavirus (HPV) prevention education on knowledge level and HPV vaccine uptake among mothers and their daughters. Forty-one mother/daughter dyads from a low-cost, faith-based clinic for the uninsured in southeastern Texas participated in the nurse practitioner-led cervical cancer prevention educational sessions. Spanish was the primary language for the majority of participating mothers. The project produced appreciable knowledge increase and HPV vaccine uptake intent. Aggregate HPV vaccine uptake numbers for the clinic increased considerably compared to HPV vaccine administration prior to educational intervention. PMID- 26813052 TI - A Systematic Review of the Transition from Homelessness to Finding a Home. AB - Homelessness is associated with premature mortality, increased morbidity, and poor quality of life. Transitioning from homelessness to housing is a complex process, particularly for individuals with mental illness. This article presents a systematic review of 26 empirical studies exploring the transition of adults from homelessness to finding a home. Seven qualitative, 14 quantitative, and 5 mixed-method studies were critically appraised and synthesized yielding persistent qualitative themes such as maintaining stability, making adjustments, and a place called home, and quantitative key categories including quality of life, sociodemographics, and housing conditions. More research is needed exploring factors related successful housing placement. PMID- 26813056 TI - [Protecting Safety During Dust Fires and Dust Explosions - The Example of the Formosa Fun Coast Water Park Accident]. AB - This paper will explore the fire and explosion characteristics of cornstarch powder as well as strategies for protecting the safety of people who are involved a dust fire or dust explosion. We discuss the 5 elements of dust explosions and conduct tests to analyze the fire and explosion characteristics of differently colored powders (yellow, golden yellow, pink, purple, orange and green). The results show that, while all of the tested powders were difficult to ignite, low moisture content was associated with significantly greater risks of ignition and flame spread. We found the auto-ignition temperature (AIT) of air-borne cornstarch powder to be between 385 degrees C and 405 degrees C, with yellow colored cornstarch powder showing the highest AIT and pink-colored cornstarch powder showing the lowest AIT. The volume resistivity of all powder samples was approximately 108 Omega.m, indicating that they were nonconductive. Lighters and cigarettes are effective ignition sources, as their lit temperatures are higher than the AIT of cornstarch powder. In order to better protect the safety of individuals at venues where cornstarch powder is released, explosion control measures such as explosion containment facilities, vents, and explosion suppression and isolation devices should be installed. Furthermore, employees that work at these venues should be better trained in explosion prevention and control measures. We hope this article is a reminder to the public to recognize the fire and explosion characteristics of flammable powders as well as the preventive and control measures for dust explosions. PMID- 26813057 TI - [The Treatment of Major Burn Injuries]. AB - Major burn injuries constitute a systemic disease. In addition to completely understanding the mechanisms of wound healing, precise burn depth and area assessment is critical to the successful management of burn injuries. The recent advancements in post-burn fluid resuscitation, tangential burn excision and grafting, effective enteral tube feeding, and aggressive sepsis treatment have helped greatly increase the survival rates for major burn injuries. However, the restricted joint motion that results from hypertrophic scar contracture remains the main challenge facing burn survivors. In conclusion, as the course of the treatment and rehabilitation is prolonged and multifaceted, a complete treatment plan is always necessary in addition to teamwork among physicians, nurses, social workers, physical therapists, and psychologists. Finally, social return is the final goal of treatment and may be achieved only through mutual support and understanding among the members of the burn treatment and rehabilitation team. PMID- 26813058 TI - [Entering the Dawn of a New Life: A Discussion of Life for Survivors of the Formosa Fun Coast Water Park Explosion]. AB - A dust explosion at the Formosa Fun Coast water park in Taiwan caused nearly 500 burn injury cases. One hundred of these cases involved burns over more than 20% of the total body surface area. This tragedy inundated hospitals across northern Taiwan with an unprecedented number of burn patients. Significant manpower and medical resources were targeted on related resuscitation and treatment efforts, with support and assistance provided by agencies and organizations nationwide. Most of the burn patients were young people in their teens and twenties, whose severe burns posed the greatest threat and challenge to their lives so far. Furthermore, their experience presented major psychosocial and physical health challenges. Patients received an array of clinical treatments such as debridement, skin grafting, dressing, and rehabilitation. Debilitating pain, skin damage, changes to body image, physical disabilities, helplessness, sadness, and anxiety have not only deeply affected the patients physically and psychologically but also created significant life stresses for their family members / companions, which requires counseling in order to facilitate emotional healing. Although burn patients gradually recover as they pass through the acute, recovery, and rehabilitation phases, they will face the challenges of lifelong rehabilitation after discharge. I hope that these young victims will take courage and be brave and strong in dealing with the difficulties and challenges of daily life and will embrace the future with hope as they enter the dawn of their new life. PMID- 26813059 TI - [The Nutrition Care of Severe Burn Patients]. AB - In addition to recent advances in burn patient care techniques such as maintaining warm circumambient temperature, the early excision of wounds, and the use of closed dressing, providing nutrition support through early feeding has proven instrumental in greatly increasing the survival rate of burn patients. Severe burns complicated by many factors initiate tremendous physiological stress that leads to postburn hypermetabolism that includes enhanced tissue catabolism, the loss of muscle mass, and decreases in the body's reservoirs of protein and energy. These problems have become the focus of burn therapy. Treating severe burns aims not only to enhance survival rates but also to restore normal bodily functions as completely as possible. Recent research evaluating the application of anabolic agents and immune-enhance formula for severe burns therapy has generated significant controversy. Inadequate caloric intake is one of the main differences among the related studies, with the effect of many special nutrients such as bran acid amides not taken into consideration. Therefore, considering the sufficiency of caloric and protein intake is critical in assessing effectiveness. Only after patients receive adequate calories and protein may the effect of special nutrients such as glutamine and supplements be evaluated effectively. PMID- 26813060 TI - [Discussion of the Roles of Medical Social Workers in the Response to the Explosion Incident at Formosa Fun Coast]. AB - Medical social workers apply the theories of "person in the environment" (PIE) and "ecological perspective" as practical foundations. Furthermore, they emphasize the people, the environment, and the interactions between these two. When burn patients from the explosion at Formosa Fun Coast were sent to hospitals, social workers not only provided care and assessed the impact on burn patients but also assisted in supporting the family members of these patients. This article discusses the various roles of social workers within different systems. In the individual system, we use Eric Erickson's theory of psychosocial development to evaluate the patient's crisis and the tasks of social workers. Secondly, in the systems of family, school, and work, we assess the relationships between a patient, his/her significant others, and caregivers as well as the interactions among sub-systems in the family. In the community and cultural systems, we focus on the social resources that may be utilized by the burn patients after discharge. Moreover, we add a time frame to examine our major tasks, including the initial stage, the middle stage, and the preparation-for discharge stage. We explore the roles of social workers, the applicable theories, and the goals for each stage. PMID- 26813061 TI - [The Mental Rehabilitation of Burn Patients After a Major Disaster]. AB - Many catastrophic disasters have happened in Taiwan over the last decade. As disaster is not a special occurrence but rather a part of the norm, mental rehabilitation should be treated as a mainstream issue in psychiatry. The internalization of emergency psychological interventions is necessary for every mental-health professional. The two primary categories of major manmade disasters in Taiwan over the past decade have been gas explosions and powder burns. Both categories have led to the serious injury of many individuals. The physical deformities and job problems faced by burn patients affect their psychiatric and emotional states both directly and indirectly. The psychiatric comorbidities of burn patients include: major depression, generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD), with GAD and PTSD comprising the most significant comorbidities in terms of numbers of diagnoses. To reduce psychological problems in the future, mental-health professionals should use appropriate psychological first aid (PFA) interventions in the early stages of treatment and rehabilitation. Mental rehabilitation is a major and comprehensive rehabilitation process. Mental-health professionals should thus use PFA to treat burn patients as well as provide long-term mental rehabilitation after discharge. PMID- 26813062 TI - [I Am an Occupational Therapist. I Will Accompany You Through the Process of Burn Rehabilitation]. AB - Burn injuries nearly always occur by accident. Burn injuries that cover large areas of the body typically cause hypertrophic scarring and joint contractures that affect the ability of the burn patient to handle normal activities of daily living. Occupational therapists begin the related interventions as early as possible, and patients require rehabilitation continuously until scar maturation. The present article provides an overview of the approach that occupational therapists should take in treating burn patients. Key elements of this approach include creating a burn rehabilitation program and helping patients achieve independence in their activities of daily living by applying individual assistive devices. The goal of this program is to allow burn patients to return to the workplace and to a normal life. We hope that this article makes more specialists aware of the proper approach to occupational therapy for burn patients and reduces the incidence of post-burn-injury sequelae. PMID- 26813063 TI - [The Effects of a Biosensing Game on the Physical Health-Related Fitness of Chronic Schizophrenic Patients]. AB - BACKGROUND: Being overweight is a common problem among chronic schizophrenic patients. However, these patients lack related exercise interventions that are both effective and convenient. PURPOSE: To explore the effects of a biosensing game intervention on the health-related fitness of chronic schizophrenic patients. METHODS: Two rehabilitation wards at a psychiatric hospital in New Taipei City were selected as the study sites. Simple random sampling was used to recruit participants. Participants in the experimental group received a 12-week biosensing game intervention, while participants in the control group received routine nursing care only. The study instruments included a demographic data sheet and anthropometric measurements. In addition, health-related fitness variables including cardiovascular endurance, muscular endurance, flexibility, and body composition (e.g., body mass index (BMI), waist-hip ratio, and body fat) were used as outcome indicators. RESULTS: A total of 35 patients participated in the experimental group and 35 patients participated in the control group. The results showed that the mean differences between the pre-test and post-test values for body weight (t=6.07, p<.01), BMI (t=5.79, p<.01), and waist-hip ratio (t=2.87, p<.05) differed significantly, with the experimental group performing better than the control group on all three indicators. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The results indicate that this 12-week intervention holds the potential to help chronic schizophrenic patients improve their health-related fitness, especially in terms of body weight, BMI, and waist-hip ratio. This study may be used as a reference for the promotion of health-related fitness programs in psychiatric institutes in the future. PMID- 26813065 TI - [The Association of the Disturbed Degree of Job Stressful Events, Physical Data and Quality of Life in Allied Personnel of Outpatient Department]. AB - BACKGROUND: Interactions between allied personnel and patients that occur during the provision of healthcare services may affect patient evaluations of the quality of medical care received. The many patients served and stresses faced every day by allied personnel may disturb their physical and psychological health and negatively affect their quality of life. PURPOSE: The aim of this study is to explore the association among stressful job-related events, physical data, and quality of life in allied personnel who work in outpatient departments. METHODS: This cross-sectional study used structured questionnaires and physical-data tests. The participants were recruited from a medical center in southern Taiwan. A total of 141 valid questionnaires were obtained, with a response rate of 88.1%. RESULTS: Larger differences between systolic and diastolic blood pressure and greater disturbed feelings toward stressful events were both associated with poorer quality of life in participants. Furthermore, the internal stressors related to the context of job and hospital sites impacted the quality of life of participants more than the external stressors related to patients or outsiders. CONCLUSIONS: The results of the present study may serve as a reference for nursing departments in medical institutions to establish contingency strategies for job stressful events and to enhance and promote the quality of life of allied personnel working in outpatient departments. PMID- 26813064 TI - [Willingness to Receive Text Message Appointment Reminders Among Patients With HIV Infection]. AB - BACKGROUND: Wireless communication technologies are increasingly being used in the fields of healthcare, with platforms such as mobile health (mHealth) being widely implemented in HIV care. The rapid expansion of mobile technologies, including smartphone applications (apps), provides a unique opportunity to effectively remind patients about regular follow-up appointments, thereby ensuring patient retention and resulting in a higher quality of care for HIV patients. PURPOSE: This study examines mobile phone users' usage patterns, application usage, and challenges associated with the use of a mobile phone reminder system in order to improve retention in HIV care among patients. METHODS: A cross-sectional descriptive study was conducted to collect data on the usage and patterns of communication technologies from 405 patients. RESULTS: This study included 384 of the 405 eligible patients, resulting in a response rate of 94.8%. A majority of participants (73.3%) indicated their willingness to receive reminders via a text message regarding their upcoming HIV clinical appointments. After adjusting for sociodemographic and clinical variables, multiple logistic regression models indicated that the willingness to receive reminder messages was independently associated with having a college-level education (AOR=2.06, 95% CI [1.05, 4.04]) and with having prior experience with using electronic reminders (AOR=4.01, 95% CI [1.51, 10.66]). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Protection of personal information was identified as the most important factor that must be addressed in order to increase patient willingness to use a cell phone reminder system. Our findings suggest that mobile technologies are a widely used and an acceptable method for improving quality of care for HIV patients. PMID- 26813066 TI - [Exploring Regular Exercise Behavior and Its Predictors in Hemodialysis Patients]. AB - BACKGROUND: Hemodialysis dialysis patients are restricted in their physical functions. These restrictions affect physical activity, psychological status, health-related quality of life, and medical prognoses. PURPOSE: The purpose of this study was to explore regular exercise behavior and its predictors in hemodialysis patients. METHODS: A cross-sectional, descriptive, correlational study design was used, and 122 subjects were recruited. Convenience sampling was conducted at an outpatient hemodialysis center of a regional teaching hospital in northern Taiwan. RESULTS: The results showed that only 23.8% of the participants engaged in regular exercise. There were statistically significant differences between the regular-exercise group and the no-regular-exercise group in terms of the 6-minute walk distance, exercise self-efficacy, fatigue, and depression. A logistic regression analysis indicated that depression (odds ratio=0.93) and exercise self-efficacy (odds ratio=1.45) were the significant predictors of regular exercise behavior for hemodialysis patients. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The present study demonstrated that low depression and high exercise self-efficacy were predictors of regular exercise behavior. The findings provide healthcare professionals with information that may be used to develop interventions that target the effective improvement of patient exercise habits. PMID- 26813067 TI - [Correlation Between Nursing Work Environment and Nurse Burnout, Job Satisfaction, and Turnover Intention in the Western Region of Mainland China]. AB - BACKGROUND: Nurse burnout and low job satisfaction are main reasons that cause nurses to leave their current position. Improving the nursing work environment may reduce the severity of job burnout and of job dissatisfaction and thus decrease the turnover intention of nursing staff. PURPOSE: The aim of this study was to explore the correlation between the nursing work environment and the outcome variables of burnout, job satisfaction, and turnover intention in the western region of Mainland China. METHODS: This is a cross-sectional descriptive study. Survey data were collected between February and December 2012 from 1,112 clinical nurses working at 83 medical, surgical, and intensive care units in 20 hospitals across the western region of Mainland China. Multistage sampling was conducted on some of the participants. The research instruments that were used included the Practice Environment Scale of the Nursing Work Index, Maslach Burnout Inventory, Nurse Job Satisfaction Scale, and the self-developed basic information and turnover intention questionnaire. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 19.0. The level of statistical significance was set at p<.05. RESULTS: Among the five dimensions of the nursing work environment, collegial nurse-physician relations earned the most favorable mean scores (3.57+/-0.68; total=4 points), whereas adequacy of staffing and resources earned the lowest (3.21+/-0.82). Over half of the participants (58.4%) reported experiencing a high level of emotional exhaustion (EE) burnout, 45.2% reported experiencing a high level of depersonalization (DP) burnout, and 24.6% reported experiencing a high level of personal accomplishment (PA) burnout. About 59% of the participants were satisfied with their work and 3.8% reported intention to leave. Participants in self-reported "favorable" work environments were less likely to report high burnout, less likely to report intention to leave, and more likely to report job satisfaction than their peers in self-reported "poor" work environments. The odds ratio (OR) values were 0.64 (EE), 0.66 (DP), 0.57 (PA), 0.19, and 2.26. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results of the present study support that the nursing work environment affects nurse burnout, job satisfaction, and turnover intention. Therefore, nursing managers should work to improve nursing work environments in order to reduce the turnover intent among their nursing staff. PMID- 26813068 TI - [An Exploration of the Pain Management Knowledge of Emergency Room Staffs and Factors of Influence]. AB - BACKGROUND: Pain has been integrated as the fifth vital sign that is a common health problem for emergency room patients. Although prior studies have addressed the effects of the pain-management knowledge of emergency room staffs on the quality of pain care, there is a dearth of research on pain management knowledge and on the factors that influence this knowledge. PURPOSE: To explore the knowledge of emergency room staffs regarding pain management and the factors that influence this knowledge. METHODS: This cross-sectional study used a self developed questionnaire to survey a convenience sample of 201 physicians and nurses from three emergency rooms in northern Taiwan. RESULTS: The average score for pain-management knowledge was 63.28 out of 100. Demographic variables including education level, professional specialty, and sources of pain education had significant effects on participants' pain-management knowledge. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The knowledge of emergency room staffs regarding pain management must be reinforced further in order to improve care quality. The factors identified that influence this knowledge may be referenced by hospitals in developing / revising pain-related continuing education, in developing pain management guidelines, and in setting the directions for future research on pain management. PMID- 26813069 TI - [Health Technology Dependency: A Concept Analysis]. AB - Health technology dependence is a widely recognized concept that refers to the utilization of technology, including drugs, equipment, instruments, and related devices, to compensate for a physical disability or to prevent the progression of a disability. Although technology may significantly prolong the life of a patient, technology may also increase the psychological pressure of these patients and the burdens of their caregivers. There is a current dearth of related research and discussions related to the concept of "health technology dependency". Therefore, the present paper uses the strategies of concept analysis described by Walker & Avant (2010) to analyze this concept. The characteristic definition of health technology dependence addresses individuals who: (1) currently live with health technology, (2) may perceive physical or psychological burdens due to health technology, and (3) feel physical and psychological well being when coping positively with their health technology dependency and, further, regard health technology as a part of their body. Further, the present paper uses case examples to help analyze the general concept. It is hoped that nurses may better understand the concept of "health technology dependency", consider the concerns of health-technology-dependent patients and their families, and develop relevant interventions to promote the well-being of these patients and their families. PMID- 26813070 TI - [Introduction of Hemodynamic Monitoring in Critical Care Units]. AB - Hemodynamic monitoring is a very important treatment in intensive care units. Measurements taken during monitoring include pulmonary artery catheter (PAC), pulse-induced contour output (PiCCO), and non-invasive hemodynamic monitoring. PAC measures cardiopulmonary parameters using the thermodilution principle. PiCCO uses transpulmonary thermodilution and pulse contour analysis to measure cardiopulmonary parameters and extra-vascular lung water, to predict lung edema, and to differentiate between cardiogenic and non-cardiogenic respiratory failure. Non-invasive hemodynamic monitoring uses the thoracic electrical bioimpedance principle to measure electrical conductivity and then calculates stroke volume and cardiopulmonary parameters using the arrangement of red blood cells. The author is a nurse in an intensive care unit who is familiar with the various methods used in hemodynamic monitoring, with preparing the related devices, with briefing patients and family members prior to procedures, with related aseptic skills, with preventing complications during the insertion procedure, and with analyzing and interpreting those parameters accurately. The issues addressed in this paper are provided as a reference for nurses and other medical personnel to choose appropriate treatments when caring for critical patients. PMID- 26813071 TI - [Applying Mishel's Uncertainty Theory to the Care of a Patient After Living-Donor Kidney Transplantation: A Care Experience]. AB - Kidney transplantation greatly benefits end-stage renal disease patients, as they no longer must bear the torment of hemodialysis. However, the effectiveness of living-donor kidney transplantation is often negatively impacted by various complications, which patients may learn to control through related self-care strategies. However, lack of information on these complications and related strategies may lead to feelings of uncertainty and worries over the prognosis. This article discusses a nursing experience with a patient who underwent living donor kidney transplantation and who suffered from immense uncertainty and prognosis-related worry. Based on the assessment framework of Mishel's uncertainty theory, the authors identified the cause of the subject's uncertainty and offered thorough information regarding post-transplant care. During the period of care, the subject gained self-care knowledge and skills. Furthermore, he learned to apply self-recording, a technique that enabled him to self-monitor the progress of his disease progress, which reduced his sense of insecurity significantly. Ultimately, the subject turned uncertainty into motivation in order to actively participate in his treatment and to maintain optimum health status. PMID- 26813072 TI - Continuous or intermittent? On the dosing schedule of sunitinib for advanced renal cell carcinoma. PMID- 26813073 TI - Robotic management of gastric stromal tumors (GIST): a single Middle Eastern center experience. AB - BACKGROUND: Surgical resection is the gold standard treatment for gastrointestinal stromal tumors (GISTs). This paper describes the authors' experience in the management of posterior gastric wall GISTs through the robotic surgical approach. METHODS: A case-series analysis for surgically resected GISTs was conducted between 2009 and 2010. All patients were followed up until mid 2015. RESULTS: Robotic resection was performed in four cases. There was no evidence of bleeding or leak in all cases. The median hospital length of stay was 8 (5-8) days. No post-operative morbidity or mortality was reported during the follow-up duration (mean +/- SD; 40.25 +/- 35 months). CONCLUSION: Findings show that the robotic assisted surgical approach to the removal of posterior wall gastric stromal tumors is associated with 100% disease-free survival rate. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26813077 TI - Extensive cicatricial alopecia in a patient with long-term trichotillomania. PMID- 26813076 TI - Melanoma therapy: Check the checkpoints. AB - Recent mutational and translational studies have revealed that the Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal regulated kinase (ERK) pathway plays a key role in melanomagenesis. Mutations in NRAS and BRAF are found in the majority of melanomas resulting in the formation of constitutively active NRAS and BRAF molecules, which leads to the proliferation and survival of melanoma cells through the activation of MEK/ERK signals. Inhibitors of BRAF or MEK significantly extend the progression-free survival and overall survival of melanoma patients compared with conventional chemotherapies. Combining BRAF and MEK inhibitors further enhances the clinical effectiveness. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is an immune checkpoint molecule that downregulates T-cell activation by binding to B7 (CD80/CD86) molecules on antigen-presenting cells. Programmed death receptor ligand 1 on melanoma cells negatively regulates T-cell function by binding to the programmed death-1 (PD-1) receptor on T cells. Antibodies against CTLA-4 and PD-1 also enhance the survival of melanoma patients. In this review, we summarize the clinical effectiveness and adverse events of the BRAF inhibitors, MEK inhibitors and anti-immune checkpoint antibodies in melanoma treatment. PMID- 26813078 TI - Stimulation of terrestrial ecosystem carbon storage by nitrogen addition: a meta analysis. AB - Elevated nitrogen (N) deposition alters the terrestrial carbon (C) cycle, which is likely to feed back to further climate change. However, how the overall terrestrial ecosystem C pools and fluxes respond to N addition remains unclear. By synthesizing data from multiple terrestrial ecosystems, we quantified the response of C pools and fluxes to experimental N addition using a comprehensive meta-analysis method. Our results showed that N addition significantly stimulated soil total C storage by 5.82% ([2.47%, 9.27%], 95% CI, the same below) and increased the C contents of the above- and below-ground parts of plants by 25.65% [11.07%, 42.12%] and 15.93% [6.80%, 25.85%], respectively. Furthermore, N addition significantly increased aboveground net primary production by 52.38% [40.58%, 65.19%] and litterfall by 14.67% [9.24%, 20.38%] at a global scale. However, the C influx from the plant litter to the soil through litter decomposition and the efflux from the soil due to microbial respiration and soil respiration showed insignificant responses to N addition. Overall, our meta analysis suggested that N addition will increase soil C storage and plant C in both above- and below-ground parts, indicating that terrestrial ecosystems might act to strengthen as a C sink under increasing N deposition. PMID- 26813079 TI - Triplets with neonatal alloimmune thrombocytopenia due to antibodies against human platelet antigen 1a. AB - BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) has been reported only rarely in twins and not at all, to our knowledge, in triplets. CASE REPORT: Nonidentical triplets were born with severe thrombocytopenia. Nadir platelet (PLT) counts were 17 * 109 , 12 * 109 , and 10 * 109 /L. NAIT was confirmed by an incompatibility for human PLT antigen (HPA)-1a and the presence of maternal anti HPA-1a. The maternal genotype was HPA-1bb and the paternal genotype was HPA-1aa; thus, all children were affected. RESULTS: PLT counts for each infant improved with the administration of random-donor PLT transfusions. All three infants also received intravenous immunoglobulin. None had major bleeding. A small isolated subependymal hemorrhage was found incidentally in one infant; this remained stable on repeat imaging. CONCLUSIONS: This is the first report of triplets with NAIT. Anti-HPA-1a is sufficiently potent to affect three infants simultaneously. Random-donor PLTs were effective in improving PLT counts in all three infants. PMID- 26813080 TI - Impact of positive fluid balance on mortality and length of stay in septic shock patients. AB - BACKGROUND: Fluid management is important in critically patients. The aim of this study was to determine the relationship between fluid balance and adverse outcomes of septic shock. METHODS: A retrospective study was conducted in the medical Intensive Care Unit (ICU) of a tertiary university hospital in Thailand, over a 7-year period. RESULTS: A total of 1048 patients with an ICU mortality rate of 47% were enrolled. The median cumulative fluid intake at 24, 48, and 72 h from septic shock onset were 4.2, 7.7, and 10.5 L, respectively. Nonsurvivors had a significantly higher median cumulative fluid intake at 24, 48, and 72 h (4.6 vs. 3.9 L, 8.2 vs. 7.1 L, and 11.4 vs. 9.9 L, respectively, P < 0.001 for all). Nonsurvivors also had a significantly higher cumulative and mean fluid balance within 72 h (5.4 vs. 4.4 L and 2.8 vs. 1.6 L, P < 0.001 for both). In multivariate logistic regression analysis, mean fluid balance quartile within 72 h, was independently associated with an increase in ICU and hospital mortality. Quartile 3 and 4 have statistically significant increases in mortality compared with quartile 1 (odds ratio [95% confidence interval] 3.04 [1.9-4.48] and 4.16 [2.49-6.95] for ICU mortality and 2.75 [1.74-4.36] and 3.16 [1.87-5.35] for hospital mortality, respectively, P < 0.001 for all). In addition, the higher amount of mean fluid balance was associated with prolonged ICU stays. CONCLUSIONS: Positive fluid balance over 3 days is associated with increased ICU and hospital mortality along with prolonged ICU stays in septic shock patients. PMID- 26813081 TI - Frequency domain near-infrared multiwavelength imager design using high-speed, direct analog-to-digital conversion. PMID- 26813082 TI - Experimental demonstration of two-photon Mueller matrix second-harmonic generation microscopy. PMID- 26813083 TI - Role of hormonal therapy for prostate cancer: perspective from Japanese experiences. AB - Hormonal therapy has been playing an important role in the treatment of prostate cancer. However, it has recently been the subject of criticism that it shows minimal effectiveness, it may reduce patients' quality of life, and induce adverse effects. On the other hand, next-generation hormonal drugs have provided new strategies for hormonal therapy to overcome advanced prostate cancer. Therefore, it is necessary to accumulate further clinical evidence concerning the efficacy and adverse effects of hormonal therapy. And, what is important for the treatment of prostate cancer is how we use hormonal therapy most effectively. This article presents a review of the possible roles of hormonal therapy for prostate cancer based upon experience in Japan. PMID- 26813085 TI - Glandular Odontogenic Cyst of Mandible: A Rare Entity. AB - Glandular odontogenic cyst (GOC) is a rare developmental odontogenic cyst. It is a slow growing and asymptomatic swelling, usually affecting middle aged men and has tendency to reoccur. Here, we report a case of GOC in the anterior portion of mandible diagnosed by histopathology. PMID- 26813084 TI - Counseling Immigrant Parents about Food and Feeding Practices: Public Health Nurses' Experiences. AB - OBJECTIVES: To describe the experiences of public health nurses (PHNs) in counseling immigrant parents on food and feeding practices at child health centers (CHCs). DESIGN AND SAMPLE: In this study employing a qualitative description (QD) approach, the participants (n = 26) were PHNs from five CHCs in the greater Oslo region of Norway. MEASURES: Data were collected through five focus group interviews and examined using qualitative content analysis. RESULTS: Counseling on food and feeding practices was an important topic in most consultations with immigrant parents. The PHNs were concerned that the child should eat ordinary, healthy food regularly. Immigrant families were often experienced as a "generic group" and the PHNs disclosed that they rarely adjusted their counseling strategy based on enquiries about families' food culture or parents' level of education or knowledge. Time constraints and language and cultural barriers were common challenges. The PHNs suggested that culturally adapted information materials and visual aids from health authorities could improve communication. CONCLUSIONS: Counseling immigrant parents on food and feeding at CHCs is often challenging for PHNs. The study findings could be used in the development of guidelines to assist PHNs in delivering culturally competent counseling about food and feeding practices. PMID- 26813086 TI - Variability of tropism and replicative capacity of two naturally occurring influenza A H9N2 viruses in cell cultures from different tissues. AB - Studies carried out on cell permissivity are of great interest to understand virus replication and pathogenicity. We described the results of a comparative analysis of replication efficiency of two naturally occurring influenza A H9N2 variants isolated from poultry and wild birds, differing by only two substitutions Q226L and T384N, in the receptor-binding site of haemagglutinin and the 380 loop region of NA proteins, respectively. Considering the overall growth of both viruses, lung cultures ensured the most efficient growth of TUN12L226N384 strain with titres up to 10(9) TCID50/ml whereas small intestine culture was highly susceptible to the TUN51Q226T384 virus reaching a titre of 10(6) TCID50/ml. The lowest replication was shown in liver cells. The addition of trypsin was essential for the replication of either virus in primary fibroblasts, but it had a marginal positive effect on virus replication in the four other culture types with maximum titres of 10(8) TCID50/ml. This means that in chicken, the proteolytic activation of the H9N2 viruses with the cleavage motif RSSR may be mediated by other endoproteases than trypsin. Further investigations should concentrate on the production of the appropriate set of viruses by a reverse genetics approach and the examination of cellular protease expression in chicken tissues. This would lead to a more complete understanding of the tropism of low pathogenic Influenza A viruses. PMID- 26813088 TI - [Evolution and changes of authentic medicinal of Rhizoma Corydalis]. AB - Rhizoma Corydalis was first recorded in Ben cao shi yi (A Supplement to Materia Medica). In the Tang and Song Dynasties, Rhizoma Corydalis used was derived from Corydalis turtschaninovii Bess. grown in the Northeast China. After the Ming Dynasty, the producing area migrated to the South and Rhizoma Corydalis was replaced by the"Maoshan Rhizoma Corydalis", that is Corydalis yanhusuo W. T. Wang nowadays, and those produced in Jiangsu and Zhejiang areas were recognized as the authentic ones. The collected time of Rhizoma Corydalis was also changed from fall to the beginning of summer. And then the processing methods in the production places underwent a change from the "critical dry", "shade dry" to the modern "boiling" method. In addition, the evaluation of quality of this medicinal was gradually changed from the location of its origin to its medicinal properties. PMID- 26813087 TI - Mental health and suicidal ideation among Chinese women who have sex with men who have sex with men (MSM). AB - In China, men who have sex with men (MSM) are the fastest growing population at risk for HIV. They face social stigma due to both MSM behavior and HIV. In addition, concern has been raised about the mental health of wives of MSM. In this cross-sectional study, the authors examine the mental health status of a sample of 135 of these women. Participants completed an Internet-administered questionnaire in Xi'an from April to June, 2012. Most were unaware at the time of marriage that their husbands were MSM. Physical abuse was frequently reported; depressive symptom and mental health (Symptom Checklist, SCL-90) scores were significantly higher than those of the general Chinese adult female population. A majority (59.8%) of women reported suicidal thoughts after discovering their husbands' MSM behavior; about 10% had attempted suicide. Multiple logistic regression revealed that women's experience with anal sex was associated with 7.8 times (95% CI: 1.3-65.9) greater odds of suicidal ideation. Also, women who demonstrated mental symptoms on the SCL-90 had 2.3 times (95% CI: 1.04-5.2) the odds of suicidal ideation. These results suggest that wives of MSM have a significant need for mental health care, suicide prevention, HIV education, and social support. PMID- 26813089 TI - [Liu Wansu's "theory of pathogenesis of six climatic qi" and its inheritance and development by Zhang Yuansu]. AB - By using the "Six climatic Qi"-wind, heat, fire, dampness, dryness, and cold-to classify diseases, to mark the innate property of viscerae, and by using the theory of engendering-restraining-overwhelming-rebellion of the six climatic Qi and its conversion to elucidate the new theme of "extreme hyperactivity might conversely overcoming the Qi it is to be converted", and expound the specificity that fire-heat is apt to combine and assimilate with wind, dampness, and dryness. Liu Wansu proposed a complete "Theory of Six Climatic Qi for Mechanism of Diseases". By inheriting the main points of Liu's such theory, Zhang Yuansu studied the theory of prescription and medication in accordance with the "Six climatic Qi cause diseases" and classified prescriptions and medicines on the basis of "Six climatic Qi", thus, developed Liu's such theory as the guideline for syndrome differential diagnosis to directly handle clinical practice. In the meantime, he also promoted the theory of visceral syndrome differential diagnosis, embodying the mutual complementary property of theories for syndrome differentiation by both viscera and six climatic Qi. PMID- 26813090 TI - [Thought of charity-persuasion and the compilation, carving and spread of medical formulary in the Qing Dynasty]. AB - Since the Song Dynasty, morality books aiming at guiding agaisnst evil and persuading charity, spread widely in the civil society. Many medical issues were categorized as encouraging kindness, hence, the thought of encouraging kindness was gradually infiltrated into the development of medical and health services. For the dissemination of medical knowledge, medical formulary became the favorite to well-doers because of its practicability in curing diseases and saving lives. Therefore, the thought of encouraging kindness infiltrated into the compilation, carving and spread of many medical formularies. The thought of encouraging kindness not only rendered a lot of doctors throw their whole life into the cause, but also attracted groups such as Confucian scholars, officers, scholar officials and many organizations such as benevolent society, benevolent association, bookshop and publishing house to join in, thus increasing the entities of spreaders, expanding the range for the spread of medical knowledge and promoting the popularization and utilization of medical knowledge in grass root society and remote area, which was helpful in dealing with the social problems such as shortage of medical resources and its uneven distribution. PMID- 26813091 TI - [Bibliometric analysis on TCM periodicals of the Republic of China]. AB - Based on analysis of the 322 kinds of TCM periodicals in the period of Republic of China , the development of such periodicals in that time can be divided into four stages. 1Sprouting Stage: from 1897 to 911; 2 Exploring Stage: from 1912 to 1927; 3Accelerating Stage: from 1928 to 1937; 4 Unstable Developing Stage, from 1938 to 1949. Periodicals of this period were mostly established by medical communities, followed by medical schools, private individuals, institutions of medical books, and medical economical units. The main source of such TCM periodicals were Zhejiang and Shanghai and then spread to Chinese inland gradually. The TCM periodicals were widely distributed, but the distribution of areas was quite uneven. PMID- 26813092 TI - [Historical origins between National Medical Association of China and Boji Hospital in Guangzhou]. AB - In 2015, National Medical Association of China, now being called the Chinese Medical Association, celebrates its centennial and Boji Hospital in Guangzhou ( also known as Canton Hospital, or the Canton Pok Tsai Hospital, and now Sun Yat sen Memorial Hospital of Sun Yat-sen University ) marks its 180th anniversary. Three major historical events establish the role of Boji Hospital in the founding and development of the National Medical Association of China during the last 100 years, viz.: 1hosting and participating in the establishment of the Medical Missionary Association of China and its official journal: the China Medical Missionary Journal; 2holding the 11th scientific sessions of the National Medical Association of China; 3nominating Dr. Wu Lien-teh as a candidate for the Nobel Prize in Physiology or Medicine in 1935 by William Warder Cadbury, the president of Boji Hospital. PMID- 26813093 TI - [The Health Station of the First Inner Ward, Peiping: Its history and legacy]. AB - The Health Station of the First Inner Ward, Peiping, was open in 1925 as a community health care institution of Peiping Health Bureau, sponsored and operated by Peking Union Medical College (PUMC) established in 1921. It was a unique demonstration project to provide the community with medical and prevention service, to implement an extraordinary educational internship of preventive medicine for PUMC students and other doctors and nurses all over the country; and to conduct applied research on the community residents'disease prevention and health promotion. Guided by the prevention thought advocated by John B. Grant, the first Chairperson of the Department of Public Health, PUMC, the station created a variety of innovative programs such as prevention-oriented public health nursing for the residents and school students, maternal and child health programs, and family health records and residents' vital surveillance statistics. The station operated for 26 years and made a significant influence on the contemporary public health in China through its unparalleled prevention education and training program and its innovative community health care demonstration. As one of the examples, it inspired the thought of primary health care raised by WHO several decades later. It provides us definitely beneficial learning as nowadays we reform health system in China. PMID- 26813094 TI - [The retrospection of nucleic acids metabolism research before the 1950s]. AB - People found the guanine in the 1840s and the nucleic acid in the 1860s. But they did not know the relationship between them. Later, people found various bases, confirmed the relationship between bases and nucleic acids, and understood the three basic processes of katabolic metabolism of nucleic acids by a number of scientists, especially with Kossel's efforts. In the 1940s, Kalckar isolated and identified some key enzymes of nucleotides metabolism, as well as Buchanan and Greenberg found the two processes of synthesis of nucleotides. The model of DNA double helix came out in 1953. Kornberg proved DNA is self-replicating in 1956. Stahl, Meselson and Vinograd found the semiconservative replication mechanism of DNA in 1958. At the same time, Ochoa found the polynucleotide phosphorylase, the enzyme can catalyze the synthesis of RNA, and synthesized RNA in 1955. Kornberg synthesized DNA on the basis of Ochoa's work in 1956. So far people found the processes of genetic information flow from DNA to RNA. It contributed to the comprehensive recognition and exploration of the pathways of genetic information and made the research of gene expression and regulation possible. PMID- 26813095 TI - [Textual research on the illustrations in ancient versions of Yi jin jing (Classic of Changing Tendon)]. AB - For a long time, the origin of inheritance of Daoyin illustrations for changing the tendon and its development are vague and lack of investigation. By investigating 48 kinds of versions of Yi jin jing (Classic of Changing Tendon), and other archaic texts of Daoyin for keeping-fit, it can be identified that there are no illustrations in extant early works of Yi jin jing. In terms of the Daoyin illustrations in the rather extensively distributed Yi jin jing, there are external exercise of Eight Section Brocade, Twelve Illustrations for Changing Tendon, 22-style yi jin jing, which are 3 different series of exercise in which the 22-style is not derived from the 12-style one. The illustrations of Daoyin for changing the tendon in the ancient versions of Yi jin jing were stemmed from the source other than the versions of Yi jin jing itself. Among them, the external exercise of Eight-section brocade is derived from many works of the Ming Dynasty, while the 12 illustrations for changing the tendon is derived from Wei sheng yao shu (Essential Art of Healthcare) in the 18th year of Xianfeng reign of the Qing Dynasty. The so-called "illustrations of external classic of yi jin jing" is but only part of the 22-style yi jin jing. PMID- 26813096 TI - [Carving and spread of Xu Shuwei's medical books in the Southern Song Dynasty]. AB - Xu Shuwei's Pu ji ben shi fang (Moxibustion in Prescription for Universal Relief) was carved for several times and disseminated to Hubei, Hunan, Zhejiang, Jiangsu, Fujian, Sichuan Provinces and the areas under the rule of the Jin ethnic minority group. While Shang han bai zheng ge (Poets of Syndrome of Exo-pathogenic Cold disease), Shang han fa wei lun (Discourse on Elucidation of Exo-pathogenic Cold Disease), and Shang han jiu shi lun (90 Discourses on Exo-pathogenic Disease) were scarcely carved or spread in its copying form with very limited distribution. Hence, Pu ji ben shi fang exerts greater influence in the Southern Song Dynasty. When analysing the citations from the Pu ji ben sgiu fang in the books of the Southern Song Dynasty, very few texts were cited from Pu ji ben shi fang. Thus, in terms of knowledge on exo-pathogenic cold disease in the Southern Song Dynasty, Xu's influence was quite limited even though he himself had deep insight into this art of disease. PMID- 26813097 TI - [Discussion on the date of Dunhuang medical scrolls]. AB - The latest closing time of the Dunhuang cave for preserving Buddhist sutra should be considered firstly in the textual research on the date of Dunhuang medical scrolls. Based on the word "Shanyao" recorded in the scroll P. 3810, it is very likely that this scroll was copied after the reign of Emperor Yingzong of the Song Dynasty, and the sealing time of Dunhuang cave for preserving Buddhist sutra was, most probably, later than 1064. The specific writing or/and copying date of each scroll could be identified by its preface, external characteristics, contents, special characters, symbols and typeface, and language feature of the scrolls. PMID- 26813098 TI - Compliance with anthelmintic treatment in the neglected tropical diseases control programmes: a systematic review. AB - Preventive chemotherapy (PCT) programmes are used to control five of the highest burden neglected tropical diseases (NTDs): soil-transmitted helminth infections (hookworm, ascariasis, and trichuriasis), lymphatic filariasis, schistosomiasis, onchocerciasis, and trachoma. Over the past decade, new resource commitments for the NTDs have enabled such programmes to intensify their control efforts, and for some diseases, to shift from goals of morbidity control to the interruption of transmission and elimination. To successfully eliminate the parasite reservoir, these programmes will undoubtedly require prolonged, high treatment coverage. However, it is important to consider that even when coverage levels reach an acceptable proportion of the target population, there may be a considerable gap between coverage (those who receive the drug) and compliance (those who actually consume the drug)-a topic of fundamental and perhaps underestimated importance. We conducted a systematic review of published literature that investigated compliance to PCT programmes for NTD control and elimination. Databases searched included PubMed/Medline, Web of Knowledge (including Web of Science), OVID, and Scopus. Data were collected on compliance rates, reasons for non-compliance, as well as the heterogeneity of compliance definitions and calculations across programmes and studies. A total of 112 studies were selected for inclusion. The findings of the review revealed substantial heterogeneity across compliance terms and definitions; an imbalance of available studies for particular disease areas and countries; and finally, a lack of longitudinal compliance studies to properly investigate the role of systematic non-compliance. The lack of consistency among reporting of compliance data can result in under- or over-estimating compliance in a population, and therefore has serious implications for setting and reaching elimination targets. Reframing of the guidelines on compliance definitions coupled with an urgent call for longitudinal research in systematic non compliance should be essential elements in the programmatic shift from control to elimination. PMID- 26813100 TI - Chemical synthesis of germanium nanoparticles with uniform size as anode materials for lithium ion batteries. AB - A simple Mg-thermal reduction reaction is reported to synthesize germanium (Ge) nanoparticles with a uniform size at a low temperature of 400 degrees C in an autoclave. The as-prepared Ge nanoparticles exhibit promising anode applications in lithium ion batteries with high capacity and excellent cycling stability. PMID- 26813099 TI - Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences. AB - Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development and reproductive function in resulting offspring (F1) or in the F2 generation. Exposure to either analgesic reduced F1 fetal GC number in both sexes and altered the tempo of fetal GC development sex-dependently, with delayed meiotic entry in oogonia but accelerated GC differentiation in males. These effects persisted in adult F1 females as reduced ovarian and litter size, whereas F1 males recovered normal GC numbers and fertility by adulthood. F2 offspring deriving from an analgesic-exposed F1 parent also exhibited sex-specific changes. F2 males exhibited normal reproductive development whereas F2 females had smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise concerns that analgesic use in pregnancy could potentially affect fertility of resulting daughters and grand daughters. PMID- 26813101 TI - Can Nitrite AMPk Up Sirt-ainty to Treat Heart Failure With Preserved Ejection Fraction? PMID- 26813103 TI - Biological Plausibility of a Link Between Arterial Ischemic Stroke and Infection With Varicella-Zoster Virus or Herpes Simplex Virus. PMID- 26813105 TI - Naphthalimide Scaffold Provides Versatile Platform for Selective Thiol Sensing and Protein Labeling. AB - Reversible thiol modifications are fundamental of cellular redox regulation. Specific thiol detection, including thiol sensing and protein thiols labeling, is critical to study such modifications. We reported the discovery of 4 methylsulfonyl-N-n-butyl-1,8-naphthalimide (MSBN), a highly selective fluorogenic probe for thiols based on the 1,8-naphthalimide scaffold. Thiols react with MSBN nearly quantitatively via nucleophilic aromatic substitution to replace the methylsulfonyl group and restore the quenched fluorescence (>100-fold increase). MSBN was employed to selectively image thiols in live cells and specifically label protein thiols with a turn-on signal to determine diverse reversible protein thiol modifications. In addition, we introduced a bulky group into the MSBN as a mass tag to create a probe MSBN-TPP, which readily discriminates the reduced thioredoxin from the oxidized one. The specific reaction of MSBN with thiols and the easy manipulation of the naphthalimide unit enable MSBN a versatile scaffold in developing novel probes for thiol-based protein bioconjugation and studying various thiol modifications. PMID- 26813106 TI - Cohnella saccharovorans sp. nov., isolated from ginseng soil. AB - A novel bacterial strain, CJ22T, was isolated from soil of a ginseng field located in Anseong, Korea. Cells of strain CJ22T were aerobic, Gram-stain positive, endospore-forming, motile, oxidase- and catalase-positive and rod shaped. The isolate grew optimally at pH 7 and 30 degrees C. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain CJ22T belonged to the genus Cohnella, displaying highest sequence similarity of 97.3% with Cohnella panacarvi Gsoil 349T. DNA-DNA relatedness between strain CJ22T and its closest relative was 35.5 % (reciprocal value, 23.8%). The phenotypic features of strain CJ22T also distinguished it from related species of the genus Cohnella. The diagnostic diamino acid in the cell-wall peptidoglycan was meso diaminopimelic acid. The major isoprenoid quinone was menaquinone MK-7 and the major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, lysyl-phosphatidylglycerol, two unidentified phospholipids and two unidentified aminophospholipids. The predominant cellular fatty acids of strain CJ22T were anteiso-C15 : 0, iso-C16:0 and C16:0. The DNA G+C content was 63.1 mol%. Based on data from this polyphasic taxonomic study, strain CJ22T is considered to represent a novel species of the genus Cohnella, for which the name Cohnella saccharovorans sp. nov. is proposed. The type strain is CJ22T (=KACC 17501T=JCM 19227T). PMID- 26813102 TI - SIRT3-AMP-Activated Protein Kinase Activation by Nitrite and Metformin Improves Hyperglycemia and Normalizes Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction. AB - BACKGROUND: Pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF) is an increasingly recognized clinical complication of metabolic syndrome. No adequate animal model of PH-HFpEF is available, and no effective therapies have been identified to date. A recent study suggested that dietary nitrate improves insulin resistance in endothelial nitric oxide synthase null mice, and multiple studies have reported that both nitrate and its active metabolite, nitrite, have therapeutic activity in preclinical models of pulmonary hypertension. METHODS AND RESULTS: To evaluate the efficacy and mechanism of nitrite in metabolic syndrome associated with PH-HFpEF, we developed a 2-hit PH HFpEF model in rats with multiple features of metabolic syndrome attributable to double-leptin receptor defect (obese ZSF1) with the combined treatment of vascular endothelial growth factor receptor blocker SU5416. Chronic oral nitrite treatment improved hyperglycemia in obese ZSF1 rats by a process that requires skeletal muscle SIRT3-AMPK-GLUT4 signaling. The glucose-lowering effect of nitrite was abolished in SIRT3-deficient human skeletal muscle cells, and in SIRT3 knockout mice fed a high-fat diet, as well. Skeletal muscle biopsies from humans with metabolic syndrome after 12 weeks of oral sodium nitrite and nitrate treatment (IND#115926) displayed increased activation of SIRT3 and AMP-activated protein kinase. Finally, early treatments with nitrite and metformin at the time of SU5416 injection reduced pulmonary pressures and vascular remodeling in the PH HFpEF model with robust activation of skeletal muscle SIRT3 and AMP-activated protein kinase. CONCLUSIONS: These studies validate a rodent model of metabolic syndrome and PH-HFpEF, suggesting a potential role of nitrite and metformin as a preventative treatment for this disease. PMID- 26813104 TI - Herpesvirus Infections and Childhood Arterial Ischemic Stroke: Results of the VIPS Study. AB - BACKGROUND: Epidemiological studies demonstrate that childhood infections, including varicella zoster virus, are associated with an increased risk of arterial ischemic stroke (AIS). Other herpesviruses have been linked to childhood AIS in case reports. We sought to determine whether herpesvirus infections, which are potentially treatable, increase the risk of childhood AIS. METHODS AND RESULTS: We enrolled 326 centrally confirmed cases of AIS and 115 stroke-free controls with trauma (29 days to 18 years of age) with acute blood samples (<=3 weeks after stroke/trauma); cases had convalescent samples (7-28 days later) when feasible. Samples were tested by commercial enzyme-linked immunosorbent assay kits for immunoglobulin M/immunoglobulin G antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, and varicella zoster virus. An algorithm developed a priori classified serological evidence of past and acute herpesvirus infection as dichotomous variables. The median (quartiles) age was 7.7 (3.1-14.3) years for cases and 10.7 (6.9-13.2) years for controls (P=0.03). Serological evidence of past infection did not differ between cases and controls. However, serological evidence of acute herpesvirus infection doubled the odds of childhood AIS, even after adjusting for age, race, and socioeconomic status (odds ratio, 2.2; 95% confidence interval, 1.2-4.0; P=0.007). Among 187 cases with acute and convalescent blood samples, 85 (45%) showed evidence of acute herpesvirus infection; herpes simplex virus 1 was found most often. Most infections were asymptomatic. CONCLUSIONS: Herpesviruses may act as a trigger for childhood AIS, even if the infection is subclinical. Antivirals like acyclovir might have a role in the prevention of recurrent stroke if further studies confirm a causal relationship. PMID- 26813107 TI - Fano resonances from gradient-index metamaterials. AB - Fano resonances - resonant scattering features with a characteristic asymmetric profile - have generated much interest, due to their extensive and valuable applications in chemical or biological sensors, new types of optical switches, lasers and nonlinear optics. They have been observed in a wide variety of resonant optical systems, including photonic crystals, metamaterials, metallic gratings and nanostructures. In this work, a waveguide structure is designed by employing gradient-index metamaterials, supporting strong Fano resonances with extremely sharp spectra. As the changes in the transmission spectrum originate from the interaction of guided modes from different channels, instead of resonance structures or metamolecules, the Fano resonances can be observed for both transverse electric and transverse magnetic polarizations. These findings are verified by fine agreement with analytical calculations and experimental results at microwave, as well as simulated results at near infrared frequencies. PMID- 26813109 TI - Constant-pH MD Simulations Portray the Protonation and Structural Behavior of Four Decapeptides Designed to Coordinate Cu(2+). AB - The cyclic decapeptide C-Asp, containing one Asp residue and three His residues, was designed by Fragoso et al. (Chem. Eur. J. 2013, 19, 2076) to bind Cu(2+) exclusively through the side chain groups and mimic copper coordination in metalloproteins. A variant of the cyclodecapeptide where Asp is substituted by Asn (C-Asn) has also been synthesized in addition to the linear ("open") counterparts of both forms (O-Asp and O-Asn), testing the importance of cyclization and the presence of Asp in Cu(2+) coordination (Chem. Eur. J. 2013, 19, 2076; Dalton Trans. 2013, 42, 6182). All peptides formed a major species at neutral pH that was able to coordinate Cu(2+) exclusively through the neutral imidazole groups and the Asp side chain, when present, with C-Asp being the most effective. A detailed description of the protonation behavior of each histidine could help understanding the coordination species being formed in the pH range and eventually further optimizing the peptide's design. However, the standard current methods (NMR titrations) are not very suited for proximal groups titrating in the same pH range. In this work, we used the stochastic titration constant-pH molecular dynamics method to calculate the protonation curves and pKa of each titrable residue in the four decapeptides, in the absence of Cu(2+) ions. The global protonation curves obtained in our simulations are in very good agreement with the existing potentiometric titration curves. The histidines are titrating very closely, and the Asp forms abundant salt bridges with the basic residues, displaying an unusually low pKa value. In addition, we could observe that the four peptides are very unstructured in the absence of copper, and not even the cyclic forms exhibit a significant beta-sheet, unlike what could be expected from the presence of beta-turn inducer units in this type of scaffold. PMID- 26813110 TI - Are the Current Doppler Echocardiography Criteria Able to Discriminate Mitral Bileaflet Mechanical Heart Valve Malfunction? An In Vitro Study. AB - Malfunction of bileaflet mechanical heart valves in the mitral position could either be due to patient-prosthesis mismatch (PPM) or leaflet obstruction. The aim of this article is to investigate the validity of current echocardiographic criteria used for diagnosis of mitral prosthesis malfunction, namely maximum velocity, mean transvalvular pressure gradient, effective orifice area, and Doppler velocity index. In vitro testing was performed on a double activation left heart duplicator. Both PPM and leaflet obstruction were investigated on a St. Jude Medical Master. PPM was studied by varying the St. Jude prosthesis size (21, 25, and 29 mm) and stroke volume (70 and 90 mL). Prosthesis leaflet obstruction was studied by partially or totally blocking the movement of one valve leaflet. Mitral flow conditions were altered in terms of E/A ratios (0.5, 1.0, and 1.5) to simulate physiologic panel of diastolic function. Maximum velocity, effective orifice area, and Doppler velocity index are shown to be insufficient to distinguish normal from malfunctioning St. Jude prostheses. Doppler velocity index and effective orifice area were 1.3 +/- 0.49 and 1.83 +/- 0.43 cm(2) for testing conditions with no malfunction below the 2.2 and 2 cm(2) thresholds (1.19 cm(2) for severe PPM and 1.23 cm(2) for fully blocked leaflet). The mean pressure gradient reached 5 mm Hg thresholds for several conditions of severe PPM only (6.9 mm Hg and mean maximum velocity value: 183.4 cm/s) whereas such value was never attained in the case of leaflet obstruction. In the case of leaflet obstruction, the maximum velocity averaged over the nine pulsed-wave Doppler locations increased by 38% for partial leaflet obstruction and 75% for a fully blocked leaflet when compared with normal conditions. Current echocardiographic criteria might be suboptimal for the detection of bileaflet mechanical heart valve malfunction. Further developments and investigations are required in order to further improve current guidelines. PMID- 26813108 TI - Systematic identification of genes with a cancer-testis expression pattern in 19 cancer types. AB - Cancer-testis (CT) genes represent the similarity between the processes of spermatogenesis and tumorigenesis. It is possible that their selective expression pattern can help identify driver genes in cancer. In this study, we integrate transcriptomics data from multiple databases and systematically identify 876 new CT genes in 19 cancer types. We explore their relationship with testis-specific regulatory elements. We propose that extremely highly expressed CT genes (EECTGs) are potential drivers activated through epigenetic mechanisms. We find mutually exclusive associations between EECTGs and somatic mutations in mutated genes, such as PIK3CA in breast cancer. We also provide evidence that promoter demethylation and close non-coding RNAs (namely, CT-ncRNAs) may be two mechanisms to reactivate EECTG gene expression. We show that the meiosis-related EECTG (MEIOB) and its nearby CT-ncRNA have a role in tumorigenesis in lung adenocarcinoma. Our findings provide methods for identifying epigenetic-driver genes of cancer, which could serve as targets of future cancer therapies. PMID- 26813111 TI - What's in a Label? Is Diagnosis the Start or the End of Clinical Reasoning? AB - Diagnostic reasoning has received substantial attention in the literature, yet what we mean by "diagnosis" may vary. Diagnosis can align with assignment of a "label," where a constellation of signs, symptoms, and test results is unified into a solution at a single point in time. This "diagnostic labeling" conceptualization is embodied in our case-based learning curricula, published case reports, and research studies, all of which treat diagnostic accuracy as the primary outcome. However, this conceptualization may oversimplify the richly iterative and evolutionary nature of clinical reasoning in many settings. Diagnosis can also represent a process of guiding one's thoughts by "making meaning" from data that are intrinsically dynamic, experienced idiosyncratically, negotiated among team members, and rich with opportunities for exploration. Thus, there are two complementary constructions of diagnosis: 1) the correct solution resulting from a diagnostic reasoning process, and 2) a dynamic aid to an ongoing clinical reasoning process. This article discusses the importance of recognizing these two conceptualizations of "diagnosis," outlines the unintended consequences of emphasizing diagnostic labeling as the primary goal of clinical reasoning, and suggests how framing diagnosis as an ongoing process of meaning-making might change how we think about teaching and assessing clinical reasoning. PMID- 26813112 TI - Macrophage migration inhibitory factor enhances lipopolysaccharide-induced fibroblast proliferation by inducing toll-like receptor 4. AB - BACKGROUND: Fibroblast proliferation is a common manifestation of chronic inflammatory diseases, including rheumatoid arthritis (RA), Crohn's disease and ulcerative colitis, etc. To alleviate patient suffering, the mechanism underlying fibroblast proliferation should be elucidated. METHODS: CCK-8 assay was used to assess the stimulatory effect of LPS and macrophage migration inhibitory factor (MIF) on fibroblast proliferation. Then, TLR4 expression on fibroblast cell membrane was carried out by confocal scanning microscopy. Finally, real-time fluorescent quantitative PCR and flow cytometry were applied to determine the expression of TLR4 after MIF challenge. RESULTS: LPS alone directly stimulated the fibroblast proliferation. In addition, MIF showed co-stimulatory effect on LPS-induced fibroblast proliferation. Interestingly, fibroblast overtly expressed TLR4 without stimulation. After MIF stimulation, real-time PCR showed TLR4 mRNA levels were increased by about 33% in the fibroblasts; in agreement, TLR4 expression on the fibroblast membrane was increased by about 20%, as shown by flow cytometry. CONCLUSIONS: These findings indicated MIF elevates TLR4 expression in fibroblast, enhancing LPS-induced cell proliferation. PMID- 26813113 TI - Isoform prefiltering improves performance of count-based methods for analysis of differential transcript usage. AB - BACKGROUND: RNA-seq has been a boon to the quantitative analysis of transcriptomes. A notable application is the detection of changes in transcript usage between experimental conditions. For example, discovery of pathological alternative splicing may allow the development of new treatments or better management of patients. From an analysis perspective, there are several ways to approach RNA-seq data to unravel differential transcript usage, such as annotation-based exon-level counting, differential analysis of the percentage spliced in, or quantitative analysis of assembled transcripts. The goal of this research is to compare and contrast current state-of-the-art methods, and to suggest improvements to commonly used work flows. RESULTS: We assess the performance of representative work flows using synthetic data and explore the effect of using non-standard counting bin definitions as input to DEXSeq, a state of-the-art inference engine. Although the canonical counting provided the best results overall, several non-canonical approaches were as good or better in specific aspects and most counting approaches outperformed the evaluated event- and assembly-based methods. We show that an incomplete annotation catalog can have a detrimental effect on the ability to detect differential transcript usage in transcriptomes with few isoforms per gene and that isoform-level prefiltering can considerably improve false discovery rate control. CONCLUSION: Count-based methods generally perform well in the detection of differential transcript usage. Controlling the false discovery rate at the imposed threshold is difficult, particularly in complex organisms, but can be improved by prefiltering the annotation catalog. PMID- 26813114 TI - Is the Degree of Hearing Loss Truly Dependent on the Site of Tympanic Membrane Perforation? PMID- 26813115 TI - Systematic Review and Meta-Analysis of the Impact of Computed Tomography-Assessed Skeletal Muscle Mass on Outcome in Patients Awaiting or Undergoing Liver Transplantation. AB - Liver transplant outcome has improved considerably as a direct result of optimized surgical and anesthesiological techniques and organ allocation programs. Because there remains a shortage of human organs, strict selection of transplant candidates remains of paramount importance. Recently, computed tomography (CT)-assessed low skeletal muscle mass (i.e. sarcopenia) was identified as a novel prognostic parameter to predict outcome in liver transplant candidates. A systematic review and meta-analysis on the impact of CT-assessed skeletal muscle mass on outcome in liver transplant candidates were performed according to the Preferred Reporting Items for Systematic Reviews and Meta Analysis guidelines. Nineteen studies, including 3803 patients in partly overlapping cohorts, fulfilled the inclusion criteria. The prevalence of sarcopenia ranged from 22.2% to 70%. An independent association between low muscle mass and posttransplantation and waiting list mortality was described in 4 of the 6 and 6 of the 11 studies, respectively. The pooled hazard ratios of sarcopenia were 1.84 (95% confidence interval 1.11-3.05, p = 0.02) and 1.72 (95% confidence interval 0.99-3.00, p = 0.05) for posttransplantation and waiting list mortality, respectively, independent of Model for End-stage Liver Disease score. Less-consistent evidence suggested a higher complication rate, particularly infections, in sarcopenic patients. In conclusion, sarcopenia is an independent predictor for outcome in liver transplantation patients and could be used for risk assessment. PMID- 26813116 TI - Epigenetics and Neuro-behavioral Modulations. PMID- 26813117 TI - Epigenetic Drugs for Multiple Sclerosis. AB - There is increasing evidence that abnormalities in epigenetic mechanisms of gene expression contribute to the development of multiple sclerosis (MS). Advances in epigenetics have given rise to a new class of drugs, epigenetic drugs. Although many classes of epigenetic drugs are being investigated, at present most attention is being paid to two classes of epigenetic drugs: drugs that inhibit DNA methyltransferase (DNMTi) and drugs that inhibit histone deacetylase (HDACi). This paper discusses the potential use of epigenetic drugs in the treatment of MS, focusing on DNMTi and HDACi. Preclinical drug trials of DNMTi and HDACi for the treatment of MS are showing promising results. Epigenetic drugs could improve the clinical management of patients with MS. PMID- 26813118 TI - Dysregulation of Acetylation Enzymes Inanimal Models of Psychostimulant use Disorders: Evolving Stories. AB - Substance use disorders are neuropsychiatric illnesses that have substantial negative biopsychosocial impact. These diseases are defined as compulsive abuse of licit or illicit substances despite adverse medicolegal consequences. Although much research has been conducted to elucidate the pathobiological bases of these disorders, much remains to be done to develop an overarching neurobiological understanding that might be translatable to beneficial pharmacological therapies. Recent advances in epigenetics promise to lead to such an elucidation. Here I provide a brief overview of observations obtained using some models of psychostimulant administration in rodents. The review identifies CREB binding protein (CBP), HDAC1, HDAC2, HADC3, HDAC4, and HDAC5 as important players in the acetylation and deacetylation processes that occur after contingent or non contingent administration of psychostimulants. These observations are discussed within a framework that suggests a need for better animal models of addiction in order to bring these epigenetic advances to bear on the pharmacological treatment of human addicts. PMID- 26813119 TI - From Clinical Application to Cognitive Enhancement: The Example of Methylphenidate. AB - Methylphenidate (MPD) is a central nervous system (CNS) stimulant, which belongs to the phenethylamine group and is mainly used in the treatment of attention deficit hyperactive disorder (ADHD). However, a growing number of young individuals misuse or abuse MPD to sustain attention, enhance intellectual capacity and increase memory. Recently, the use of MPD as a cognitive enhancement substance has received much attention and raised concerns in the literature and academic circles worldwide. The prescribing frequency of the drug has increased sharply as consequence of the more accurate diagnosis of the ADHD and the popularity of the drug itself due to its beneficial short-term effect. However, careful monitoring is required, because of possible abuse. In this review different aspects concerning the use of MPD have been approached. Data showing its abuse among college students are given, when the drug is prescribed short term beneficial effects and side effects are provided; moreover studies on animal models suggesting long lasting negative effects on healthy brains are discussed. Finally, emphasis is given to the available formulations and pharmacology. PMID- 26813121 TI - Metabotropic Glutamate 2/3 Receptors and Epigenetic Modifications in Psychotic Disorders: A Review. AB - Schizophrenia and Bipolar Disorder are chronic psychiatric disorders, both considered as "major psychosis"; they are thought to share some pathogenetic factors involving a dysfunctional gene x environment interaction. Alterations in the glutamatergic transmission have been suggested to be involved in the pathogenesis of psychosis. Our group developed an epigenetic model of schizophrenia originated by Prenatal Restraint Stress (PRS) paradigm in mice. PRS mice developed some behavioral alterations observed in schizophrenic patients and classic animal models of schizophrenia, i.e. deficits in social interaction, locomotor activity and prepulse inhibition. They also showed specific changes in promoter DNA methylation activity of genes related to schizophrenia such as reelin, BDNF and GAD67, and altered expression and function of mGlu2/3 receptors in the frontal cortex. Interestingly, behavioral and molecular alterations were reversed by treatment with mGlu2/3 agonists. Based on these findings, we speculate that pharmacological modulation of these receptors could have a great impact on early phase treatment of psychosis together with the possibility to modulate specific epigenetic key protein involved in the development of psychosis. In this review, we will discuss in more details the specific features of the PRS mice as a suitable epigenetic model for major psychosis. We will then focus on key proteins of chromatin remodeling machinery as potential target for new pharmacological treatment through the activation of metabotropic glutamate receptors. PMID- 26813120 TI - REM sleep and its Loss-Associated Epigenetic Regulation with Reference to Noradrenaline in Particular. AB - Sleep, an essential physiological process, has been divided into rapid eye movement sleep (REMS) and non-REMS (NREMS) in higher animals. REMS is a unique phenomenon that unlike other sleep-waking states is not under voluntary control. Directly or indirectly it influences or gets influenced by most of the physiological processes controlled by the brain. It has been proposed that REMS serves house-keeping function of the brain. Extensive research has shown that during REMS at least noradrenaline (NA)-ergic neurons must cease activity and upon REMS loss, there is increased level of NA in the brain, which then induces many of the REMS loss associated acute and chronic effects. The NA level is controlled by many bio-molecules, which are regulated at the molecular and transcriptional levels. Similarly, NA may also directly or indirectly modulate synthesis and levels of many molecules, which in turn may affect physiological processes. The burgeoning field of behavioral neuro-epigenetics has gained importance in recent years and explains the regulatory mechanisms underlying several behavioral phenomena. As REMS and its loss associated changes in NA modulates several pathophysiological processes, in this review we have attempted to explain on one hand how the epigenetic mechanisms regulating the gene expression of factors like tyrosine hydroxylase (TH), monoamine oxidase (MAO), noradrenaline transporter (NAT) control NA levels and on the other hand, how NA per se may affect other molecules in neural circuitry at epigenetic level resulting in behavioral changes in health and diseases. An understanding of these events will expose the molecular basis of REMS and its loss-associated pathophysiological changes; which are presented as testable hypothesis for confirmation. PMID- 26813125 TI - [Pay attention to research on prevention and treatment of sleep disturbances at high altitude]. PMID- 26813124 TI - Polaronic metal state at the LaAlO3/SrTiO3 interface. AB - Interplay of spin, charge, orbital and lattice degrees of freedom in oxide heterostructures results in a plethora of fascinating properties, which can be exploited in new generations of electronic devices with enhanced functionalities. The paradigm example is the interface between the two band insulators LaAlO3 and SrTiO3 that hosts a two-dimensional electron system. Apart from the mobile charge carriers, this system exhibits a range of intriguing properties such as field effect, superconductivity and ferromagnetism, whose fundamental origins are still debated. Here we use soft-X-ray angle-resolved photoelectron spectroscopy to penetrate through the LaAlO3 overlayer and access charge carriers at the buried interface. The experimental spectral function directly identifies the interface charge carriers as large polarons, emerging from coupling of charge and lattice degrees of freedom, and involving two phonons of different energy and thermal activity. This phenomenon fundamentally limits the carrier mobility and explains its puzzling drop at high temperatures. PMID- 26813126 TI - [Pay attention to their sleep health problems: the bed partners of patients with sleep-disordered breathing]. PMID- 26813122 TI - Compartmentalized Platforms for Neuro-Pharmacological Research. AB - Dissociated primary neuronal cell culture remains an indispensable approach for neurobiology research in order to investigate basic mechanisms underlying diverse neuronal functions, drug screening and pharmacological investigation. Compartmentalization, a widely adopted technique since its emergence in 1970s enables spatial segregation of neuronal segments and detailed investigation that is otherwise limited with traditional culture methods. Although these compartmental chambers (e.g. Campenot chamber) have been proven valuable for the investigation of Peripheral Nervous System (PNS) neurons and to some extent within Central Nervous System (CNS) neurons, their utility has remained limited given the arduous manufacturing process, incompatibility with high-resolution optical imaging and limited throughput. The development in the area of microfabrication and microfluidics has enabled creation of next generation compartmentalized devices that are cheap, easy to manufacture, require reduced sample volumes, enable precise control over the cellular microenvironment both spatially as well as temporally, and permit highthroughput testing. In this review we briefly evaluate the various compartmentalization tools used for neurobiological research, and highlight application of the emerging microfluidic platforms towards in vitro single cell neurobiology. PMID- 26813127 TI - [Application value of four different questionnaires in the screening of patients with obstructive sleep apnea]. AB - OBJECTIVE: To evaluate the clinical utility of four questionnaires of Berlin, STOP, STOP-Bang (SBQ) and Epworth Sleepiness Scale (ESS) in the screening of patients with obstructive sleep apnea (OSA). METHODS: A total of 350 consecutive patients (302 males and 48 females, 19-86 years old, average(42.9 +/- 11.0) years old) with suspected OSA who underwent an overnight polysomnography (PSG) were recruited into this study. Four questionnaires of Berlin, STOP, SBQ and ESS were completed. Based on the severity of OSA which was determined by apnea-hypopnea index (AHI), the patients were classified into four groups of primary snoring (<5 events/h), mild (5-<15 events/h), moderate (15-<30 events/h) and severe OSA (>= 30 events/h). Sensitivity, specificity, positive predictive values, negative predictive values and the area under the receiver operating characteristics curve of four questionnaires were calculated. RESULTS: Using mild-moderate-severe (>= 5 events/h), moderate-severe (>= 15 events/h), and severe (>= 30 events/h) OSA as cutoffs, SBQ had the highest sensitivity (94%, 94% and 95%, respectively). Berlin Questionnaire had the largest area under the receiver operating characteristics curve (0.784, 0.732, and 0.771, respectively). ESS had the lowest sensitivity (43%, 45% and 48%, respectively). CONCLUSIONS: Compared to the PSG, SBQ questionnaire has the highest sensitivity, but lower specificity; in contrast, Berlin questionnaire may have better accuracy. PMID- 26813128 TI - [Value of actigraphy and oximetry for diagnosing sleep apnea-hypopnea syndrome]. AB - OBJECTIVE: To explore the value of actigraphy and oximetry for diagnosing sleep apnea-hypopnea syndrome (SAHS). METHODS: Suspected SAHS subjects were enrolled from sleep center of Peking University People's Hospital between December 2013 and September 2014. Light-out and light-on were simultaneously recorded for polysomnography (PSG), actigraphy and oximetry. Actigraphy was used to correct total sleep time (TST) for oximetry. Oxygen desaturation index (ODI4), namely the times of pulse oxygen saturation (SpO2) drop>=4% per hour, was detected by oximetry. ODIA was used instead of ODI4 with TST corrected by actigraphy. Receiver operating characteristic (ROC) curve was used for evaluating the value of ODI4 and ODIA for diagnosing SAHS and cut-off value was calculated. Paired t test or signed rank t-test was used for data acquired using actigraphy or oximetry compared with data acquired by PSG. Sensitivity and specificity were calculated using fourfold table. Disease severity of SAHS was classified by apnea hypopnea index (AHI) detected by PSG. If AHI<5/h, SAHS was not considered. 5 <15/h was classified as mild, 15-<30/h was classified as moderate and AHI>=30/h was classified as severe. RESULTS: Among 213 SAHS subjects, 38 of them were normal, 34 of them were mild, 51 were moderate and 90 were severe. Compared with PSG, actigraphy can correctly estimate TST in non-SAHS (P=0.408) and mild SAHS groups (P=0.949); while in moderate and severe SAHS groups, TSTs detected by actigraphy were shorter than TSTs acquired by PSG ((405+/-51) vs (419+/-40) min and (399 +/- 62) vs (422 +/- 60) min) (both P<0.05). Area under ROC curve (AUC) of ODI4 for diagnosing SAHS was 0.956 using a cut-off value of 5; the AUC of ODIA for diagnosing SAHS was 0.951 with a cut-off value of 5 as well. The sensitivity of ODI4 for mild, moderate and severe SAHS was 80.6%, 66.7% and 58.9% respectively, all with a specificity of 100%. After adjusting TST with actigraphy, the sensitivity of ODIA for mild, moderate and severe SAHS was 84.0%, 73.8 % and 68.9%, with specificity of 94.7%, 100% and 99.2% respectively. CONCLUSIONS: Actigraphy can correctly estimate TST in non-SAHS and mild SAHS groups. ODI4 can be used for diagnosing SAHS. After correcting TST by actigraphy, the sensitivity of ODIA is higher. PMID- 26813129 TI - [Pilot study on the differences of young male's sleep structure and quality between indigenous Tibetans and longtime Han residents in high altitude area]. AB - OBJECTIVE: To compare young males' sleep quality and structure between native Tibetans and longtime Han residents. METHODS: A total of 14 male Tibetans and 11 male Hans at an altitude of 3 780 m were enrolled in this study. Tibetans were native highlanders with a mean age of (32.0 +/- 9.1) years. Han subjects were born and living in high altitude with a mean age of (36.6 +/- 7.6) years. All subjects were monitored by Polysomnography(PSG), and the differences of sleep structure and quality between the two groups were compared according to the international standard. RESULTS: The sleep efficiency (93.1% +/- 3.9% vs 85.7% +/ 4.2%) and nocturnal oxygen saturation (SpO(2)) (89.4% +/- 2.0% vs 84.6% +/- 4.3%) in Tibetans was significantly higher than those in Hans (both P<0.05). The number of awakening ((1.9 +/- 0.8) vs (4.1 +/- 1.3)/h) and micro-awakening ((23.4 +/- 5.8) vs (28.7 +/- 4.1)/h), the oxygen reduction index ((11.7 +/- 4.8) vs (16.3 +/- 7.5)/h), apnea hypoventilation index (AHI) ((5.8 +/- 2.3) vs (9.6 +/- 4.2)/h) and average heart rate ((66.9 +/- 8.3) vs (79.9 +/- 6.7)/min) of Tibetans were significantly lower than Hans (all P<0.05). Tibetans had longer slow wave sleep (20.1% +/- 7.2% vs 8.8% +/- 3.3%) and the Hans had longer stage 2 of non rapid eye movement (NREM) (31.1% +/- 11.9% vs 18.4% +/- 6.7%) and shallow sleep (76.1 +/- 11.7 vs 70.8 +/- 11.2) (all P<0.05). CONCLUSION: Tibetans have better sleep quality and higher sleep efficiency than Han residents at high altitude. PMID- 26813130 TI - [Relationship of visceral adiposity index with serum aminotransferase and nonalcoholic fatty liver disease in patients with sleep apnea]. AB - OBJECTIVE: To evaluate the relationship of visceral adiposity index (VAI) with serum aminotransferase levels and incidence of nonalcoholic fatty liver disease (NAFLD) in patients with sleep apnea (SA). METHODS: Between January 2011 and December 2014, participants who were referred from Fujian Provincial Sleep disordered Breathing (SDB) Clinic Center with repeated snoring or a clinical suspicion of SDB were recruited. All individuals underwent polysomnography (PSG) testing and an abdominal ultrasonography scan during this period. They were classified into four groups by apnea-hypopnea index (AHI), non-SA group, mild, moderate and severe group (AHI<5/h, 5-<15/h, 15-<30/h, >=30/h, respectively). The differences in SA-related parameters, serum aminotransferase and VAI were tested, and the correlations of VAI with indices of PSG and serum aminotransferase were analyzed using Spearman coefficient. Receiver operating characteristic (ROC) curve was conducted to obtain a cut-off value of VAI for predicting NAFLD. Afterwards, logistic regression was performed to analyze VAI's predictive ability regarding incidence of NAFLD in SDB patients. RESULTS: A total of 152 participants including 110 males and 42 females were analyzed, with mean age (51.1+/-11.3) years. There were 20 subjects in non-SA group, 31 in mild, 39 in moderate and 62 in severe group, with 92 NAFLD patients and 60 controls. No differences in sex, age, alkaline phosphatase were observed among groups according to AHI. However, body mass index, waist circumference, AHI, lowest oxygen saturation, oxygen desaturation index(ODI), VAI, alanine aminotransferase (ALT), aspartate aminotransferase, gamma glutamyltransferase (GGT) and incidence of NAFLD were significantly different among groups. Significant positive relations were observed between VAI and AHI (beta=0.222, P=0.006), ODI (beta=0.216, P=0.008), ALT (beta=0.237, P=0.003), GGT (beta=0.238, P=0.003). As shown in ROC curve, the cut-off point of VAI for predicting NAFLD was 1.59 in all individuals. SDB patients with VAI>=1.59 tended to have significantly greater risk in incidence of NAFLD (OR=4.550, P<0.001). CONCLUSION: VAI was closely associated with increased serum aminotransferase levels and incidence of NAFLD. PMID- 26813131 TI - [Association of the extra-gonadal manifestations with different pathogenic gene mutations in male patients with congenital hypogonadotropic hypogonadism]. AB - OBJECTIVE: To explore the relationships between pathogenic gene mutations and extra-gonadal manifestations in male patients with congenital hypogonadotropic hypogonadism (CHH). METHODS: A total of 15 genes were screened in 259 CHH patients by massively parallel DNA sequencing. The identified pathogenic mutations were confirmed by Sanger polymerase chain reaction (PCR). The extra gonadal features in all patients were recorded. RESULTS: Gene mutations were detected in 83 (32.0%) patients, which included FGFR1 (n=20), PROKR2 (n=19), CHD7 (n=16), KAL1 (n=14) and other genes (n=14), such as PROK2, FGF8, GNRHR, KISS1R, NELF and WDR11. Patients with KAL1 mutation displayed CHH related family history (n=5) and obesity (n=3). Patients with FGFR1 mutation presented with short stature (n=3), testicular hydrocele (n=2), lip-palate cleft (n=2) and dental dysplasia (n=1). Patients without detectable mutations may also exhibit obesity, mental retardation and short stature. CONCLUSIONS: CHH patients may present with extra-gonadal manifestations, including anosmia, obesity, dental dysplasia, short stature and mental retardation. An obscure relationships could be found between the clinical features and different gene mutations, but it is difficult to speculate the types of pathogenic gene mutations according to these extra-gonadal manifestations. PMID- 26813132 TI - [Association of single nucleotide polymorphisms of IL-6 gene with longevity in Uyghurs in Xinjiang]. AB - OBJECTIVE: To investigate whether the variations of genes encoding pro inflammatory cytokines is associated with longevity in Uyghurs in Xinjiang. METHODS: A total of 240 individuals aged >=90 years from Xinjiang Uyghur Autonomous Region were enrolled between 1999 and 2012 as the longevity group, 92 unrelated individuals from the same area who died naturally at the age of 59-73 in the same period were selected as the control group. Seven single nucleotide polymorphisms (SNPs) of 4 genes (tumor necrosis factor (TNF)-alpha(rs1800629), IL 6(rs1800796, rs10499563), C-reactive protein (CRP) (rs2808630, rs1205) and IL 1beta(rs1143623, rs16944)) were genotyped. Logistic regression was applied to assess the association between each individual SNP and longevity in case-control analyses. RESULTS: The distribution of C allele of rs1800796 in the longevity group (0.298) was lower than that in the control group (0.435) with statistical significance (P=0.001). The distributions of the other 6 genetic variations between the longevity group and the control group showed no statistically significant differences (all P>0.05). CT genotype of rs1800796 was positively associated with longevity (Padd=0.002, OR=1.983, 95%CI: 1.296-3.023), while no significant association was noted between other genotypes and longevity. CONCLUSIONS: SNP of rs1800796 of IL-6 gene may be significantly associated with longevity in Uyghurs in Xinjiang. CT genotype of rs1800796 is significantly associated with longevity. C allele of rs1800796 may be a negative factor for longevity. PMID- 26813123 TI - Alzheimer's disease: Targeting the Cholinergic System. AB - Acetylcholine (ACh) has a crucial role in the peripheral and central nervous systems. The enzyme choline acetyltransferase (ChAT) is responsible for synthesizing ACh from acetyl-CoA and choline in the cytoplasm and the vesicular acetylcholine transporter (VAChT) uptakes the neurotransmitter into synaptic vesicles. Following depolarization, ACh undergoes exocytosis reaching the synaptic cleft, where it can bind its receptors, including muscarinic and nicotinic receptors. ACh present at the synaptic cleft is promptly hydrolyzed by the enzyme acetylcholinesterase (AChE), forming acetate and choline, which is recycled into the presynaptic nerve terminal by the high-affinity choline transporter (CHT1). Cholinergic neurons located in the basal forebrain, including the neurons that form the nucleus basalis of Meynert, are severely lost in Alzheimer's disease (AD). AD is the most ordinary cause of dementia affecting 25 million people worldwide. The hallmarks of the disease are the accumulation of neurofibrillary tangles and amyloid plaques. However, there is no real correlation between levels of cortical plaques and AD-related cognitive impairment. Nevertheless, synaptic loss is the principal correlate of disease progression and loss of cholinergic neurons contributes to memory and attention deficits. Thus, drugs that act on the cholinergic system represent a promising option to treat AD patients. PMID- 26813133 TI - [Effectiveness and safety of pulsatile GnRH pump therapy on female patients with IHH]. AB - OBJECTIVE: To investigate the therapeutic effect of pulsatile GnRH (gonadorelin) pump on female patients with idiopathic hypogonadotropic hypogonadism (IHH). METHODS: In this retrospective study, five female IHH patients were recruited. Patients were treated with pulsatile gonadorelin (10 ug per 90 min) via a pump for at least 12 weeks. Serum gonadotropins and sex steroid levels were measured, and menses were recorded. RESULTS: After one-week treatment, luteinizing hormone (LH) level increased from (2.2 +/- 2.0) U/L to (5.4 +/- 2.5) U/L (P=0.028), follicle-stimulating hormone(FSH) level increased from (3.7 +/- 2.7) U/L to(6.3 +/- 1.0) U/L (P=0.162), and estradiol (E2) level increased from (58 +/- 13) pmol/L to (260 +/- 97) pmol/L (P=0.011). Menstrual bleeding was observed in 4 patients after starting treatment for 35-55 days and two natural pregnancies were reported. No menstrual bleeding was reported in another patient. The frequency of pulsatile GnRH had to be adjusted according to endogenous GnRH secretion during the follicular phase of normal women and regular menses were induced. CONCLUSIONS: Pulsatile GnRH is effective in treating female IHH. A constant frequency of pulsatile GnRH is suitable for most of IHH patients. However, for those who failed to produce regular menses, adjusting pulsatile frequency to imitate the physiological rhythm of GnRH may be an alternative option. PMID- 26813135 TI - [The effect of propofol and sevoflurane on the perioperative immunity in patients under laparoscopic radical resection of colorectal cancer]. AB - OBJECTIVE: To compare the effect of propofol and sevoflurane on perioperative immunity and surgical outcomes in patients undergoing laparoscopic radical resection of colorectal cancer. METHODS: During September 2012 to April 2014 in Sir Run Run Shaw Hospital, thirty patients scheduled for laparoscopic colorectal cancer radical resection were randomly assigned into two groups: propofol TCI anesthesia and sevoflurane inhale anesthesia. Venous blood was taken before induction, on finishing the surgery and 24 h after surgery for lymphocyte subtype study by flow cytometry. Postoperative outcomes including intestinal obstruction, urine retention, anastomotic fistula and incision healing, antibiotic using time, hospital-stay time were compared. RESULTS: In the sevoflurane group, the percentage of CD3+, CD4+ and CD19+ subtype were increased immediately after surgery ((64.0 +/- 13.5)%, (37.5 +/- 11.8)%, (12.3 +/- 4.5)%) comparing to preoperative level ((59.0 +/- 12.0)%, (33.0 +/- 8.3)%, (9.9 +/- 4.3)%) (t= 3.423, 2.543, 2.768 respectively, all P<0.05), while NK cell percentage was significantly decreased ((22.9 +/- 13.2)% vs (30.7 +/- 11.9)%) (t=-3.444, P<0.01). The changes of CD3+, CD19+ and NK cell remained significant at 24 h ((63.5 +/- 9.3)%, (13.0 +/- 4.0)%, (22.5 +/- 7.2)%) (t=2.961, 3.502, -4.621 respectively, all P<0.05). In the propofol group, the levels of CD3+, CD4+, CD19+ and CD4+ /CD8+ ratio were significantly increased after surgery ((69.4 +/- 9.7)%, (43.2 +/- 9.2)%, (15.2 +/- 7.4)%, 1.9 +/- 0.9) comparing to the preoperative levels ((61.9 +/- 13.6)%, (34.6 +/- 8.9)%, (10.4 +/- 4.5)%, 1.5 +/- 0.7) (t= 4.732, 6.132, 3.688, 4.640 respectively, all P<0.01), and NK cell was significantly decreased ((14.7 +/- 10.2)% vs (27.2 +/- 14.3)%) (t=-4.935, P<0.01). These changes were similar to that of the sevoflurane group. At 24 h in the propofol group, comparing with those after surgery, CD3+, CD4+ and CD4+ /CD8+ ratio were significantly decreased ((63.6 +/- 12.3)%, (36.0 +/- 8.7)%, 1.5 +/- 0.6) (t=-2.879, -3.682, -3.340 respectively, all P<0.05), and returned to baseline when comparing to the preoperative level (t= 0.858, 0.758, -0.074 respectively, all P>0.05). NK cell began to recover at 24 h ((22.2 +/- 12.6)%) comparing to the postoperative level (t= 2.941, P<0.05), but was still lower than the baseline (t=-2.249, P<0.05). Also, for all the above data, there were no difference between the two groups at any points (all P>0.05). There were no difference in hospital-stay time, antibiotic using time, the time to anal exhaust or defecate, postoperative fever, incision infection, neither other complications such as intestinal obstruction, urine retention, anastomotic fistula or intraperitoneal infection (all P>0.05). The incision infection rate was 0 in the propofol group while 14.3% in the sevoflurane group, which was quite clinically obvious though not statistically significant. CONCLUSIONS: Propofol may have less or shorter impact on immunity. However, whether anesthesia with propofol could be superior to that with sevoflurane for patients' immune function is still undetermined and needs further study. PMID- 26813134 TI - [Clinical significance of serum bone metabolic markers in diagnosis and monitoring of myeloma bone disease]. AB - OBJECTIVE: To explore the significance of serum bone metabolic markers in the diagnosis and monitoring of multiple myeloma bone disease(MBD). METHODS: Thirty six newly diagnosed multiple myeloma (MM) patients who were treated in Department of Hematology, Tianjin Medical University General Hospital from January 2013 to December 2014 were collected. Bone morbidity was graded into two stages according to the radiographic evaluation of the skeleton: stage A (n=12) included patients with no lytic lesions or with osteoporosis alone; stage B (n=24) included patients with osteolytic lesions and/or a pathological fracture. All the patients achieved partial or complete remission after treated with bortezomib + dexamethasone + zoledronic acid regimen. A total of 25 aged- and gender-matched healthy individuals were enrolled in this study as controls. The levels of serum tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), carboxy-terminal cross linking telopeptide of type I collagen (CTX), osteocalcin (OCN), and procollagen I amino-terminal propeptide (PINP) were investigated by ELISA and electrochemiluminescence immunoassay (ECLIA). The differences of these bone metabolic markers before and after treatment, and at different stages of bone disease were observed. RESULTS: The value of TRACP-5b in the newly diagnosed MM was significantly higher than that in the healthy controls and after treatment(median 4.16 vs 2.63 U/L, P=0.014; 4.16 vs 2.61 U/L, P=0.037). Serum level of CTX in the newly diagnosed MM patients was significantly decreased after treatment (median: 0.26 vs 1.05 ug/L, P=0.003). The ratio of CTX/OCN and CTX/PINP decreased after treatment, but there were no significant differences (both P>0.05). The pretreatment level of serum TRACP-5b in stage B patients was higher than that of the healthy controls (median: 4.20 vs 2.63 U/L, P=0.015). The levels of serum CTX in stage A and stage B patients were both higher than that of the healthy controls (median: 1.16 vs 0.48 ug/L, P=0.002; 0.88 vs 0.48 ug/L, P=0.040). The levels of serum OCN and PINP were higher in stage A patients compared with stage B patients, but there were no significant differences (both P>0.05). The ratio of CTX/OCN and CTX/PINP of stage A and stage B patients all increased compared with those of the healthy controls, but there were no significant differences (all P>0.05). CONCLUSIONS: Bone damage of MM patients is improved after effective treatment, but bone imbalance still exists, indicating that the treatment of MBD is a long process. Abnormal serum levels of TRACP-5b and CTX are found before positive X-ray findings in MBD, suggesting that these biochemical markers could be used as indices for early diagnosis of MBD. PMID- 26813136 TI - [Clinicopathological analysis of 14 cases of early stage dermatofibrosarcoma protuberans]. AB - OBJECTIVE: To improve understanding of the clinical and histopathological features of early stage dermatofibrosarcoma protuberans(DFSP). METHODS: The clinical data and histopathological findings of 14 cases of early stage DFSP diagnosed in Institute of Dermatology, Chinese Academy of Medical Sciences from 2008 to 2014 were retrospectively analyzed. RESULTS: The patients were mostly young people. The average age of onset was 21 years old. The progress was slow. The initial main manifestations were well-circumscribed atrophic erythema or sclerotic plaque, and subcutaneous nodules appeared gradually based on the erythema. Histopathology showed a small number of tumor cells in the upper dermis, aligned parallel to the epidermis with wavy arrangement, while the tumor cells exhibited typical DFSP changes in the lower dermis and the subcutaneous fat. The tumor cells expressed vimentin and CD34, but not S100 and CD68. CONCLUSIONS: Because the clinical and histological features are atypical, the early stage of DFSP is easily misdiagnosed as various benign diseases. Repeated biopsy and combining clinical features with pathological findings are helpful for diagnosis. PMID- 26813137 TI - [Analysis of the relationship between mitochondrial DNA deletion and clinical complexity of mitochondrial disease]. AB - OBJECTIVE: To analyze the relationship between proportion of mitochondrial DNA 4 977 bp deletion (DeltamtDNA(4977)) or copy number in blood and the clinical complexity to find the pathogenesis of mitochondrial disease. METHODS: A total of 160 patients with mitochondrial disease and 101 healthy controls of Peking University First Hospital from December 2003 to December 2013 were collected in this study. Their peripheral blood showed no hot-point mutation which detected by polymerase chain reaction-restriction fragment length polymorphism. All the patients were divided into younger group (age<10y) and elder group (10y<=age<20y). The incidence of DeltamtDNA(4977) was detected by real-time quantitative PCR. Internal gene was used to calculate the number of mitochondrial DNA in each cell. Statistical analysis were carried out by the independent t test, one-way ANOVA and Spearman's bivariate correlation analysis. RESULTS: DeltamtDNA (4977) proportion in the younger group was (2.66 +/- 0.63)% and in the elder group was (3.09 +/- 0.74)%, both of them were higher than that of healthy control group with the same age (the younger group: t=8.57, P<0.01; the elder group: t=4.38, P<0.01); DeltamtDNA(4977) copy number per cell in the younger group was (2.79 +/- 0.50) copy and in the elder group was (2.97 +/- 0.48) copy, both of them were higher than that of healthy control group with the same age (the younger group: t=4.50, P<0.01; the elder group: t=-3.67, P<0.01). The DeltamtDNA (4977) proportion was positively correlated with the complexity of the mitochondrial disease(the younger group: r=0.519, P<0.01; the elder group: r=0.772, P<0.01). The DeltamtDNA (4977) copy number per cell was positively correlated with the complexity of the mitochondrial disease(the younger group: r=0.389, P<0.01; the elder group: r=0.607, P<0.05). However, the total mtDNA copy number per cell was negatively correlated with the complexity of the mitochondrial disease (the younger group: r=-0.260, P<0.01; the elder group: r= 0.430, P<0.05). CONCLUSIONS: The proportion or copy number of DeltamtDNA (4977) or total mtDNA copy number in blood are correlated with the complexity of mitochondrial diseases, especially the proportion of DeltamtDNA (4977). PMID- 26813138 TI - [A multicenter randomized controlled clinical trial of Ligation of the Intersphincteric Fistula Tract Plus Bioprosthetic Anal Fistula Plug in the treatment of chronic anal fistula]. AB - OBJECTIVE: To evaluate the effectiveness and safety of Ligation of the Intersphincteric Fistula Tract Plus Bioprosthetic Anal Fistula Plug (LIFT-plug) in the treatment of chronic anal fistula. METHODS: A total of 239 patients (199 males, 40 females) with chronic anal fistula were recruited from 5 hospitals between March 2011 and April 2013. These patients were randomly assigned to the experimental group (n=119) treated with LIFT-plug or the control group (n=120) treated with LIFT. The follow-up period was 180 days. The collected data included healing rate, the median healing time, the recurrence rate, the Visual Analogue Scale (VAS), the incontinence rate, and the safety indicators associated with the anal fistula plug. RESULTS: The healing rate of the experimental group was better than the control group (96.5% vs 83.7%, P<0.05). The median healing time of the experimental group was 22 days and the latter was 30 days (P<0.05). By the end of the follow-up period, there was no recurrence found in the two groups. The VAS and the incontinence rate had no statistically significant difference between the two groups. There were no adverse events associated with the anal fistula plug in the experimental group. CONCLUSION: LIFT-plug is simple, less invasive, and with shorter healing time and more satisfactory healing rate in treating chronic anal fistula compared with LIFT. PMID- 26813139 TI - [The incidence and risk factors of male urinary tract infection following invasive urodynamic investigation]. AB - OBJECTIVE: To assess the prevalence of male urinary tract infection (UTI) after invasive urodynamic studies and to determinate the risk factors by evaluating the clinical characteristics and urodynamic parameters of patients. METHODS: Six hundred and seventy-one consecutive men were recruited. All patients accepted urine routine tests and(or)urine culture three times. The first culture and routine tests were carried out in the 2 to 4 weeks before urodynamic studies by using clean-catch midstream urine (MSU) or catheter urine specimen. The second urine routine test was carried out at the start of examinations and the last urine culture were carried out in 48-72 hours after the investigations. Male patients with negative results (leucocytes <15 cells/ul and <10(5) colony-forming units per milliliter [cfu/ml]) in 1(st) and 2(nd) time received a standard urodynamic investigation. The investigations of the remaining patients were postponed until the urinary tract infection had been treated. RESULTS: The prevalence of urinary tract infection before urodynamic investigation (with positive results in 1(st) and 2(nd) urine test) was 7.3%, and the prevalence after the investigation in patients without UTI before examination was 10.3%. Bladder outlet obstruction (BOO), age >= 65 years, and diabetes were the risk factors for UTI after urodynamic investigation. The most common uropathogens in the urinary tract infections after the urodynamic investigation were Escherichia coli (53.1%, 34/64) and Enterococcus faecalis (17.2%, 11/64). CONCLUSION: Despite a stringent standard operation protocol, the prevalence of UTI in male patients caused by urodynamic examination is about 10%. For the high-risk patients with BOO, older age, and diabetes, prophylactic antibiotic treatment before or after procedure may be necessary. PMID- 26813140 TI - [The methods and techniques of treatment of renal pedicle vessels during retroperitoneal laparoscopic nephrectomy]. AB - OBJECTIVE: To introduce the methods and techniques of treatment of renal pedicle vessels during retroperitoneal laparoscopic nephrectomy. METHODS: Retroperitoneal laparoscopic nephrectomies were performed in 580 cases in our hospital from March 2004 to May 2014. Different measures were adopted to seek and manage bilateral renal pedicle vessels. The operative time, intraoperative blood loss, duration of postoperative drainage, and postoperative hospital stay were analyzed retrospectively. RESULTS: 12 cases were converted to open surgery due to severe bleeding of renal pedicle vessels. Mean operative time was (100.5 +/- 24.8) min, mean intraoperative blood loss was (90.4 +/- 26.5) ml, duration of postoperative drainage was (3.6 +/- 1.2) d, and mean postoperative hospital stay were (7.4 +/- 2.8) d. CONCLUSION: Different managing for bilateral renal pedicle vessels will help to decrease operative time and improve the safety of the surgery. PMID- 26813141 TI - [The effects of repetitive extragenic palindromic sequences from Brucella melitensis DNA on the toll-like receptor 9-mediated interferon-alpha production]. AB - OBJECTIVE: To screen the repetitive extragenic palindromic sequences with activation of toll-like receptor 9 (TLR9) activity from Brucella melitensis DNA, providing new ideas and new targets for prevention and treatment of brucellosis. METHODS: Bioinformatics methods were used to detect repetitive extragenic palindromic (REP) sequences from Brucella melitensis DNA. The studied REPs were selected and synthesized. RAW264.7 was cultured and transfected with REPs mediated by lipofectamine 3000. Additionally, TLR9-siRNA was used to downregulate TLR9 expression. The content of interferon-alpha (IFN-alpha) in the supernatant was then measured by ELISA. RESULTS: A total of 2 200 REP sequences in Brucella melitensis DNA were identified. Twelve REP sequences were synthesized for further detecting of the TLR9 agonistic activity. IFN-alpha expression in RAW264.7 treated with M2, M3, M4, M5, M6, M7, M9, M12 were (26.944 +/- 1.868), (46.461 +/- 2.562), (34.980 +/- 2.055), (43.016 +/- 2.162), (62.533 +/- 4.031), (67.125 +/- 5.069), (18.908 +/- 1.633), (39.572 +/- 2.465) pg/ml respectively, which significantly increased when compared with the negative control group [(12.594 +/ 1.338) pg/ml, t=10.817, 20.295, 15.812, 20.724, 20.365, 18.016, 5.180, 16.660, all P<0.05]. Additionally, TLR9-siRNA can significantly decrease the levels of IFN-alpha in RAW264.7 treated with M6. CONCLUSION: REP sequences presented in Brucella melitensis DNA are able to induce IFN-alpha expression through TLR9, which can be helpful for the understanding of pathogenesis and immunity of Brucella melitensis. PMID- 26813142 TI - A novel pathway for the production of H2 S by DAO in rat jejunum. AB - BACKGROUND: Hydrogen sulfide (H2 S) is endogenously generated from L-cysteine (L Cys) by the enzymes cystathionine-beta-synthase (CBS) and cystathionine-gamma Lyase (CSE). Hydrogen sulfide is also produced from D-cysteine (D-Cys) by D-Amino acid oxidase (DAO). METHODS: The H2 S production was measured by the methylene blue assay. The expression of DAO was investigated by Western blotting and immunohistochemistry. The short-circuit current (Isc) was recorded using the Ussing chamber technique. KEY RESULTS: The epithelium in rat jejunum possesses DAO, and generates H2 S. D-cysteine, originally used as a negative control for L Cys, significantly increases the H2 S release, which is inhibited by I2CA, an inhibitor of DAO. In vitro study by Ussing chamber technique reveals that D-Cys decreases the Isc across the epithelium of the rat jejunum and enhances the Na(+) -coupled L-alanine transport. CONCLUSIONS & INFERENCES: A novel pathway for the production of H2 S by DAO exists in rat jejunum. PMID- 26813143 TI - Controlled Phase and Tunable Magnetism in Ordered Iron Oxide Nanotube Arrays Prepared by Atomic Layer Deposition. AB - Highly-ordered and conformal iron oxide nanotube arrays on an atomic scale are successfully prepared by atomic layer deposition (ALD) with controlled oxidization states and tunable magnetic properties between superparamagnetism and ferrimagnetism. Non-magnetic alpha-Fe2O3 and superparamagnetic Fe3O4 with a blocking temperature of 120 K are in-situ obtained by finely controlling the oxidation reaction. Both of them exhibit a very small grain size of only several nanometers due to the nature of atom-by-atom growth of the ALD technique. Post annealing alpha-Fe2O3 in a reducing atmosphere leads to the formation of the spinel Fe3O4 phase which displays a distinct ferrimagnetic anisotropy and the Verwey metal-insulator transition that usually takes place only in single crystal magnetite or thick epitaxial films at low temperatures. The ALD deposition of iron oxide with well-controlled phase and tunable magnetism demonstrated in this work provides a promising opportunity for the fabrication of 3D nano-devices to be used in catalysis, spintronics, microelectronics, data storages and bio applications. PMID- 26813144 TI - A cotton miRNA is involved in regulation of plant response to salt stress. AB - The present study functionally identified a new microRNA (microRNA ovual line 5, miRNVL5) with its target gene GhCHR from cotton (Gossypium hirsutum). The sequence of miRNVL5 precursor is 104 nt long, with a well developed secondary structure. GhCHR contains two DC1 and three PHD Cys/His-rich domains, suggesting that GhCHR encodes a zinc-finger domain-containing transcription factor. miRNVL5 and GhCHR express at various developmental stages of cotton. Under salt stress (50-400 mM NaCl), miRNVL5 expression was repressed, with concomitant high expression of GhCHR in cotton seedlings. Ectopic expression of GhCHR in Arabidopsis conferred salt stress tolerance by reducing Na(+) accumulation in plants and improving primary root growth and biomass. Interestingly, Arabidopsis constitutively expressing miRNVL5 showed hypersensitivity to salt stress. A GhCHR orthorlous gene At2g44380 from Arabidopsis that can be cleaved by miRNVL5 was identified by degradome sequencing, but no confidential miRNVL5 homologs in Arabidopsis have been identified. Microarray analysis of miRNVL5 transgenic Arabidopsis showed six downstream genes (CBF1, CBF2, CBF3, ERF4, AT3G22920, and AT3G49200), which were induced by salt stress in wild-type but repressed in miRNVL5-expressing Arabidopsis. These results indicate that miRNVL5 is involved in regulation of plant response to salt stress. PMID- 26813145 TI - Bi-directional series-parallel elastic actuator and overlap of the actuation layers. AB - Several robotics applications require high torque-to-weight ratio and energy efficient actuators. Progress in that direction was made by introducing compliant elements into the actuation. A large variety of actuators were developed such as series elastic actuators (SEAs), variable stiffness actuators and parallel elastic actuators (PEAs). SEAs can reduce the peak power while PEAs can reduce the torque requirement on the motor. Nonetheless, these actuators still cannot meet performances close to humans. To combine both advantages, the series parallel elastic actuator (SPEA) was developed. The principle is inspired from biological muscles. Muscles are composed of motor units, placed in parallel, which are variably recruited as the required effort increases. This biological principle is exploited in the SPEA, where springs (layers), placed in parallel, can be recruited one by one. This recruitment is performed by an intermittent mechanism. This paper presents the development of a SPEA using the MACCEPA principle with a self-closing mechanism. This actuator can deliver a bi directional output torque, variable stiffness and reduced friction. The load on the motor can also be reduced, leading to a lower power consumption. The variable recruitment of the parallel springs can also be tuned in order to further decrease the consumption of the actuator for a given task. First, an explanation of the concept and a brief description of the prior work done will be given. Next, the design and the model of one of the layers will be presented. The working principle of the full actuator will then be given. At the end of this paper, experiments showing the electric consumption of the actuator will display the advantage of the SPEA over an equivalent stiff actuator. PMID- 26813146 TI - Heart rate variability in untreated newly diagnosed temporal lobe epilepsy: Evidence for ictal sympathetic dysregulation. AB - OBJECTIVE: To compare heart rate variability (HRV) parameters in newly diagnosed and untreated temporal lobe epilepsy (TLE) between the interictal, preictal, ictal, and postictal states. METHODS: HRV parameters were extracted from single lead electrocardiography data collected during video-electroencephalography (EEG) recordings from 14 patients with newly diagnosed TLE in a resting, awake, and supine state. HRV parameters in the time and frequency domains included low frequency (LF), high frequency (HF), standard deviation of all consecutive R wave intervals (SDNN), and square root of the mean of the sum of the squares of differences between adjacent R wave intervals (RMSSD). Cardiovagal index (CVI), cardiosympathetic index (CSI), and approximate entropy (ApEn) were also studied. RESULTS: Frequency domain analysis showed significantly higher preictal, ictal, and postictal LF/HF ratio compared to the interictal state. Similarly, the LF component increased progressively and was significantly higher during the ictal state compared to interictal and preictal states. RR interval values were lower in the ictal state compared to basal and preictal states and in the postictal state compared to the preictal state. Interictal RMSSD was significantly higher compared to all other states, and ictal SDNN was significantly higher compared to all other states. Ictal CSI was significantly higher compared to preictal and interictal states, whereas preictal CVI was lower than in basal and ictal states. In addition, ictal ApEn was significantly lower than interictal and preictal ApEn. Interictal CVI was lower in left TLE compared to right TLE. In addition, in left TLE, ictal CVI was higher than interictal CVI, whereas in right TLE, CVI was lower in the preictal state compared to all other states. SIGNIFICANCE: Our data suggest an ictal sympathetic overdrive with partial recovery in the postictal state. Higher sympathetic tone and vagal tone imbalance may induce early autonomic dysfunction and increase cardiovascular risk in patients affected by TLE. PMID- 26813147 TI - Drug carriers based on highly protein-resistant materials for prolonged in vivo circulation time. AB - Long-circulating drug carriers are highly desirable in drug delivery system. However, nonspecific protein adsorption leaves a great challenge in drug delivery of intravenous administration and significantly affects both the pharmacokinetic profiles of the carrier and drugs, resulting in negatively affect of therapeutic efficiency. Therefore, it is important to make surface modification of drug carriers by protein-resistant materials to prolong the blood circulation time and increase the targeted accumulation of therapeutic agents. In this review, we highlight the possible mechanism of protein resistance and recent progress of the alternative protein-resistant materials and their drug carriers, such as poly(ethylene glycol), oligo(ethylene glycol), zwitterionic materials, and red blood cells adhesion. PMID- 26813148 TI - An Indirect Action Contributes to C-Fos Induction in Paraventricular Hypothalamic Nucleus by Neuropeptide Y. AB - Neuropeptide Y (NPY) is a well-established orexigenic peptide and hypothalamic paraventricular nucleus (PVH) is one major brain site that mediates the orexigenic action of NPY. NPY induces abundant expression of C-Fos, an indicator for neuronal activation, in the PVH, which has been used extensively to examine the underlying NPY orexigenic neural pathways. However, PVH C-Fos induction is in discordance with the abundant expression of NPY receptors, a group of inhibitory Gi protein coupled receptors in the PVH, and with the overall role of PVH neurons in feeding inhibition, suggesting a mechanism of indirect action. Here we showed that the ability of NPY on C-Fos induction in the PVH was blunted in conditions of insulin deficiency and fasting, a condition associated with a high level of NPY and a low level of insulin. Moreover, insulin insufficiency blunted C-Fos induction in the PVH by fasting-induced re-feeding, and insulin and NPY induced c Fos induction in the same group of PVH neurons. Finally, NPY produced normal C Fos induction in the PVH with disruption of GABA-A receptors. Thus, our results revealed that PVH C-Fos induction by NPY is mediated by an indirect action, which is at least partially mediated by insulin action, but not GABA-A receptors. PMID- 26813149 TI - Improved Catalytic Activity and Stability of a Palladium Pincer Complex by Incorporation into a Metal-Organic Framework. AB - A porous metal-organic framework Zr6O4(OH)4(L-PdX)3 (1-X) has been constructed from Pd diphosphinite pincer complexes ([L-PdX](4-) = [(2,6-(OPAr2)2C6H3)PdX](4 ), Ar = p-C6H4CO2(-), X = Cl, I). Reaction of 1-X with PhI(O2CCF3)2 facilitates I(-)/CF3CO2(-) ligand exchange to generate 1-TFA and I2 as a soluble byproduct. 1 TFA is an active and recyclable catalyst for transfer hydrogenation of benzaldehydes using formic acid as a hydrogen source. In contrast, the homogeneous analogue (t)Bu(L-PdTFA) is an ineffective catalyst owing to decomposition under the catalytic conditions, highlighting the beneficial effects of immobilization. PMID- 26813150 TI - Toxic Shock Syndrome Caused by Methicillin-Resistant Staphylococcus aureus (MRSA) After Expander-Based Breast Reconstruction. AB - OBJECTIVE: Toxic shock syndrome is a rare but life-threatening complication after plastic surgery procedures. METHODS: We experienced 2 cases of toxic shock syndrome after expander-based breast reconstruction caused by methicillin resistant Staphylococcus aureus. RESULTS: The first patient took a severe clinical course due to the delayed diagnosis and treatment, and the second patient recovered rapidly after the early diagnosis and treatment based on our experience of the first case. Fever, rash, and gastrointestinal symptoms (diarrhea and/or vomiting) were characteristic and important for the early diagnosis of toxic shock syndrome. CONCLUSIONS: Considering the increased prevalence of methicillin-resistant Staphylococcus aureus, we should suspect methicillin-resistant Staphylococcus aureus in cases of toxic shock syndrome that occur postoperatively, and the empiric administration of vancomycin should be initiated in such cases. PMID- 26813151 TI - Evaluation and treatment of hypernatremia: a practical guide for physicians. AB - Hypernatremia (serum sodium concentration >145 mEq/L) is a common electrolyte disorder with increased morbidity and mortality especially in the elderly and critically ill patients. The review presents the main pathogenetic mechanisms of hypernatremia, provides specific directions for the evaluation of patients with increased sodium levels and describes a detailed algorithm for the proper correction of hypernatremia. Furthermore, two representative cases of hypovolemic and hypervolemic hypernatremia are presented along with practical clues for their proper evaluation and treatment. Accurate diagnosis and appropriate treatment is crucial since undercorrection or overcorrection of hypernatremia are both associated with poor patients' prognosis. PMID- 26813152 TI - Bulk Crystallization in a SiO2/Al2O3/Y2O3/AlF3/B2O3/Na2O Glass: Fivefold Pseudo Symmetry due to Monoclinic Growth in a Glassy Matrix Containing Growth Barriers. AB - A glass with the mol% composition 17 Y2O3.33 Al2O3.40 SiO2.2 AlF3.3 Na2O.2 CeF3.3 B2O3 is heat treated at 1000 degrees C for 6-24 h. This results in the surface nucleation and growth of YAG. Nucleation and growth of star-shaped alumina and later of monoclinic beta-Y2Si2O7 and orthorhombic delta-Y2Si2O7 are additionally observed in the bulk. Phase identification and localization are performed by electron backscatter diffraction (EBSD) as well as TEM analysis. The monoclinic beta-Y2Si2O7 observed in the bulk occurs in the form of large, crystal agglomerates which range from 50 to 120 MUm in size. The individual crystals are aligned along the c-axis which is the fastest growing axis. Ten probability maxima are observed in the pole-figures illustrating the rotation of orientations around the c-axes indicating a fivefold symmetry. This symmetry is caused by multiple twinning which results in a high probability of specific orientation relationships with rotation angles of ~36 degrees , ~108 degrees (also referred to as the pentagon angle) and ~144 degrees around the c-axis. All these rotation angles are close to the multiples of 36 degrees which are required for an ideal fivefold symmetry. This is the first report of a fivefold symmetry triggered by the presence of barriers hindering crystal growth. PMID- 26813153 TI - An economic cost analysis of emergency department key performance indicators in Ireland. AB - OBJECTIVES: High quality data is fundamental to using key performance indicators (KPIs) for performance monitoring. However, the resources required to collect high quality data are often significant and should usually be targeted at high priority areas. As part of a study of 11 emergency department (ED) KPIs in Ireland, the primary objective of this study was to estimate the relative cost of collecting the additional minimum data set (MDS) elements for those 11 KPIs. METHODS: An economic cost analysis focused on 12 EDs in the Republic of Ireland. The resource use data were obtained using two separate focus group interviews. The number of available MDS elements was obtained from a sample of 100 patient records per KPI per participating ED. Unit costs for all resource use were taken at the midpoint of the relevant staff salary scales. RESULTS: An ED would need to spend an estimated additional &OV0556;3561 per month on average to capture all the MDS elements relevant to the 11 KPIs investigated. The additional cost ranges from 14.8 to 39.2%; this range is 13.9-32.3% for small EDs, whereas the range for medium EDs is 11.7-40%. Regional EDs have a higher additional estimated cost to capture all the relevant MDS elements (&OV0556;3907), compared with urban EDs (&OV0556;3353). CONCLUSION: The additional cost of data collection, contingent on that already collected, required to capture all the relevant MDS elements for the KPIs examined, ranges from 14.8 to 39.2% per KPI, with variation identified between regional and urban hospitals. PMID- 26813155 TI - Construction of pillar[6]arene-based CO2 and UV dual-responsive supra-amphiphile and application in controlled self-assembly. AB - A gas and photo dual-responsive host-guest recognition motif was established based on a water-soluble pillar[6]arene and an azobenzene derivative in an aqueous medium. This smart inclusion complex was further applied for the construction of a supra-amphiphile, which could reversibly self-assemble into vesicles upon UV/vis irradiation or bubbling with N2/CO2. PMID- 26813156 TI - Pseudoverticin B, a novel geldanamycin analog obtained as new cell cycle inhibitor from Streptomyces pseudoverticillus YN17707. AB - Pseudoverticin B (1), a novel naturally occurring geldanamycin analog with cell cycle inhibitory activity, was isolated from the fermentation broth of Streptomyces pseudoverticillus YN17707, together with the known ansamycin antibiotic, hydroquinone geldanamycin (2), through bioassay-guided fractionation procedures. The structure of compound 1 was elucidated by spectroscopic methods, being characterized by an ansa bridge, same as that in geldanamycin and a novel hydroquinone-derived moiety. Compounds 1 and 2 arrested the cell cycle of tsFT210 cells at the G0/G1 phase with the minimum inhibitory concentration values of 10.1 and 20.2 MUmolL(-1), respectively. PMID- 26813154 TI - New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel. AB - BACKGROUND: By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations. METHODS: We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel. RESULTS: We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90% threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold. CONCLUSIONS: Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals. PMID- 26813157 TI - Fluorescence Lifetime Imaging of Nanoflares for mRNA Detection in Living Cells. AB - The expression level of tumor-related mRNA can reveal significant information about tumor progression and prognosis, so specific mRNA in cells provides an important approach for biological and disease studies. Here, fluorescence lifetime imaging of nanoflares in living cells was first employed to detect specific intracellular mRNA. We characterized the lifetime changes of the prepared nanoflares before and after the treatment of target mRNA and also compared the results with those of fluorescence intensity-based measurements both intracellularly and extracellularly. The nanoflares released the cy5-modified oligonucleotides and bound to the targets, resulting in a fluorescence lifetime lengthening. This work puts forward another dimension of detecting specific mRNA in cells and can also open new ways for detection of many other biomolecules. PMID- 26813158 TI - Health-related quality of life association with work-related stress and social support among female and male disabled employees. AB - Few studies have focused on adverse relations of job strain to health in disabled employees by gender. In this study, the author explores gender differences in work-related stress, social support, and health-related quality of life (HRQoL) among 106 disabled employees in an electronics manufacturing plant during 2012 2013, using questionnaire data on demographics, perceived work-related stress, the Beck Depression Inventory, the Chinese version of the Job Content Questionnaire (C-JCQ), and HRQoL. The prevalence of stress related to workload, colleagues, and supervisor were 26.4%, 14.1%, and 8.5%, respectively. Disabled females had higher scores for psychological job demand than male disabled employees (p = .0219). Increasing psychological job demand scores were adversely related to physical function scores (beta = -1.6) in males, whereas increasing decision latitude scores were positively related to role-limitation due to physical function (beta = 2.3), general health (beta = 1.2), vitality (beta = 1.3), role-limitation due to emotional health (beta = 2.6), and mental health (beta = 0.9) scores in females. These results provide a better understanding of the HRQoL in female and male disabled workers, allowing for the development of stress-prevention programs specific for gender in disabled laborers. PMID- 26813159 TI - Urinary adverse effects of pelvic radiotherapy. AB - OBJECTIVE: Radiation is an integral part of the treatment of many pelvic tumors. The cellular death induced by radiotherapy (RT) benefits cancer control but can also result in adverse effects (AEs) on the organ being treated or those adjacent to it. RT for cancers of the pelvis (bladder, prostate, rectum, uterus or cervix) can result in AEs in the urinary tract. While the acute urinary AEs of pelvic RT are well described, late AEs are less well characterized. The burden of treatment for late AEs may be large given the prevalence of tumors in the pelvis and the high utilization of RT to treat them. REVIEW: For prostate cancer, grade 1 and 2 urinary AEs following external beam radiation therapy (EBRT) are reported to occur in 20-43% and 7-19%, respectively, with a follow up of 10 years. Three-year cumulative risk for grade >=2 urinary AEs is 28-30%. Following brachytherapy (BT), rates of urinary AEs at 5 years are reported to be 36%, 24%, 6.2% and 0.1% for Radiation Therapy Oncology Group (RTOG) grade 1, 2, 3, and 4, respectively. For bladder cancer, with a median follow-up of 5 years, 7-12% of patients who receive RT experience urinary AEs of grade 3 or more. For cervical cancer, there remains a 0.25% per year risk of severe AEs for at least 25 years following RT, and ureteral stricture is a well-described AE. For endometrial cancer, severe urinary AEs are rare, but at 13 years of follow up, patients report a significantly worse quality of life with respect to urinary function. In rectal cancer, preoperative RT has a lower risk of AEs than postoperative RT, and few urinary AEs are reported in the literature. CONCLUSIONS: Urinary AEs can manifest long after RT, and there is a paucity of studies describing rates of these long term AEs. It is important that the possible complications of RT are recognized by providers and properly communicated to patients so that they are able to make informed decisions about their cancer treatment. PMID- 26813161 TI - Metazoan parasites of Brama australis from southern Chile: a tool for stock discrimination? AB - The metazoan parasites of 403 specimens of the southern ray's bream Brama australis from three localities in southern Chile (Lebu 36 degrees 70' S; 73 degrees 40' W, Calbuco 41 degrees 50' S; 73 degrees 08' W and Punta Arenas 53 degrees 10' S; 70 degrees 50' W) were recorded. More than 23 400 parasite specimens belonging to 12 taxa were registered. Metazoan parasites were dominated by the copepod Hatschekia conifera, constituting 97% of the total number of parasites; the larval cestode Hepatoxylon trichiuri was the second most important parasite (2.1% of the total number of parasites). The remaining 10 species constituted <1% of the metazoan parasites. Parasitological evidence, based on univariate and multivariate analysis, does not support the existence of discrete stocks in the studied zone. PMID- 26813160 TI - Neuron-derived FGF10 ameliorates cerebral ischemia injury via inhibiting NF kappaB-dependent neuroinflammation and activating PI3K/Akt survival signaling pathway in mice. AB - FGF10 is a member of fibroblast growth factors (FGFs). We previously showed that FGF10 protects neuron against oxygen-glucose deprivation injury in vitro; however, the effect of FGF10 in ischemic stroke in vivo is unknown. In the present study, we showed that FGF10 was mainly expressed in neurons but not astrocytes, and detected FGF10 in mouse cerebrospinal fluid. The FGF10 levels in neurons culture medium and cell lysate were much higher than those in astrocytes. FGF10 expression in brain tissue and FGF10 level in CSF were increased in mouse middle cerebral artery occlusion (MCAO) model. Administration of FGF10 into lateral cerebroventricle not only decreased MCAO-induced brain infarct volume and neurological deficit, but also reduced the number of TUNEL-positive cells and activities of Caspases. Moreover, FGF10 treatment depressed the triggered inflammatory factors (TNF-alpha and IL-6) and NF-kappaB signaling pathway, and increased phosphorylation of PI3K/Akt signaling pathway. Blockade of PI3K/Akt signaling pathway by wortmannin and Akt1/2-kinase inhibitor, partly compromised the neuroprotection of FGF10. However, blockade of PI3K/Akt signaling pathway did not impair the anti-inflammation action of FGF10. Collectively, our results demonstrate that neuron-derived FGF10 ameliorates cerebral ischemia injury via inhibiting NF-kappaB-dependent neuroinflammation and activating PI3K/Akt survival signaling pathway in mice. PMID- 26813162 TI - Role of envelope N-linked glycosylation in Ross River virus virulence and transmission. AB - With an expanding geographical range and no specific treatments, human arthritogenic alphaviral disease poses a significant problem worldwide. Previous in vitro work with Ross River virus (RRV) demonstrated that alphaviral N-linked glycosylation contributes to type I IFN (IFN-alphabeta) induction in myeloid dendritic cells. This study further evaluated the role of alphaviral N-linked glycans in vivo, assessing the effect of glycosylation on pathogenesis in a mouse model of RRV-induced disease and on viral infection and dissemination in a common mosquito vector, Aedes vigilax. A viral mutant lacking the E1-141 glycosylation site was attenuated for virus-induced disease, with reduced myositis and higher levels of IFN-gamma induction at peak disease contributing to improved viral clearance, suggesting that glycosylation of the E1 glycoprotein plays a major role in the pathogenesis of RRV. Interestingly, RRV lacking E2-200 glycan had significantly reduced replication in the mosquito vector A. vigilax, whereas loss of either of the E1 or E2-262 glycans had little effect on the competence of the mosquito vector. Overall, these results indicate that glycosylation of the E1 and E2 glycoproteins of RRV provides important determinants of viral virulence and immunopathology in the mammalian host and replication in the mosquito vector. PMID- 26813163 TI - Autopsy. PMID- 26813164 TI - Bone and Soft Tissue Pathology. PMID- 26813165 TI - Breast Pathology. PMID- 26813166 TI - Cardiovascular Pathology. PMID- 26813167 TI - Cytopathology. PMID- 26813168 TI - Dermatopathology. PMID- 26813169 TI - Education. PMID- 26813170 TI - Endocrine Pathology. PMID- 26813171 TI - Gastrointestinal Pathology. PMID- 26813172 TI - Genitourinary Pathology. PMID- 26813173 TI - Gynecologic and Obstetric Pathology. PMID- 26813174 TI - Head and Neck Pathology. PMID- 26813176 TI - Infectious Disease Pathology. PMID- 26813175 TI - Hematopathology. PMID- 26813177 TI - Informatics. PMID- 26813179 TI - Liver. PMID- 26813178 TI - Kidney/Renal Pathology. PMID- 26813180 TI - Neuropathology and Ophthalmic Pathology. PMID- 26813181 TI - Pancreas and Biliary Tree. PMID- 26813182 TI - Pathobiology. PMID- 26813183 TI - Pediatric Pathology. PMID- 26813184 TI - Pulmonary Pathology. PMID- 26813186 TI - Techniques. PMID- 26813185 TI - Quality Assurance. PMID- 26813188 TI - Disclosure Information. PMID- 26813189 TI - Renal evaluation with B-mode and Doppler ultrasound in captive tufted capuchins (Sapajus apella). AB - BACKGROUND: This study aimed to evaluate, by B-mode ultrasound and Doppler ultrasound, the kidneys of one Neotropical primate maintained in captivity. METHODS: Ten adult intact tufted capuchins (Sapajus apella) were evaluated. The morphometric parameters of both kidneys were evaluated and kidney volumes calculated. Color Doppler was used to evaluate renal vascular architecture and to identify arteries of the left kidney. Spectral Doppler was used to measure peak systolic velocity, end-diastolic velocity, and resistive index (RI). RESULTS: Both kidneys presented homogeneous cortical echogenicity and homogeneous echotexture with preserved corticomedullary differentiation. There was no statistically significant difference between right and left kidneys for all morphometric parameters. RI of the left renal, interlobar, and arcuate arteries were, respectively, 0.75 (SD, 0.07), 0.70 (SD, 0.08), and 0.70 (SD, 0.06). CONCLUSIONS: Both kidneys showed similar morphometric parameters by B-mode ultrasound, whereas RI by spectral Doppler decreased progressively from renal artery to interlobar and arcuate arteries. PMID- 26813190 TI - Validity and reliability of the Chronic Oral Mucosal Diseases Questionnaire in a UK population. AB - OBJECTIVE: The objective of this study was to investigate the validity and reliability of a the Chronic Oral Mucosal Diseases Questionnaire in a UK population METHODS: Two hundred patients with chronic oral mucosal disease (oral lichen planus, recurrent aphthous stomatitis, mucous membrane pemphigoid, pemphigus vulgaris) were enrolled in this study from the Oral Medicine Department of University College London Hospitals Trust (UCLHT) Eastman Dental Hospital. Individuals were interviewed using Oral Health Impact Profile (OHIP-14), Visual Analogue Scale (VAS) and Chronic Oral Mucosal Diseases Questionnaire (COMDQ), and the construct validity and internal reliability were examined. RESULTS: Of the 200 study participants, 100 respondents had oral lichen planus, 42 had recurrent aphthous stomatitis and 58 had vesiculobullous conditions (mucous membrane pemphigoid or pemphigus vulgaris). With regard to construct validity, a moderate to good degree of convergent validity was found between OHIP-14 and VAS and most subscales and the total COMDQ score except the patient support subscale of COMDQ (0.21-0.37). CONCLUSION: COMDQ is a valid and reliable patient-reported outcome measure for patients with chronic oral mucosal diseases in a UK population. It can be considered a valuable instrument in both clinical practice and in oral medicine research. PMID- 26813193 TI - Nkisi Nkondi (Nail Figure): Congolese, Republic of the Congo. PMID- 26813194 TI - Clinicians Embrace 3D Printers to Solve Unique Clinical Challenges. PMID- 26813203 TI - Implementation Science: A Potential Catalyst for Delivery System Reform. PMID- 26813204 TI - A PIECE OF MY MIND. I Feel Witty, Oh So Witty. PMID- 26813206 TI - Recommendations for Screening for Depression in Adults. PMID- 26813205 TI - Inconclusive Results of Randomized Trials of Prenatal Vitamin D for Asthma Prevention in Offspring: Curbing the Enthusiasm. PMID- 26813207 TI - JAMA Welcomes the US Preventive Services Task Force. PMID- 26813208 TI - Effect of Vitamin D3 Supplementation During Pregnancy on Risk of Persistent Wheeze in the Offspring: A Randomized Clinical Trial. AB - IMPORTANCE: Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring, but the preventive effect of vitamin D supplementation to pregnant women is unknown. OBJECTIVE: To determine whether supplementation of vitamin D3 during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, single-center, randomized clinical trial conducted within the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort. Enrollment began March 2009 with a goal of 708 participants, but due to delayed ethical approval, only 623 women were recruited at 24 weeks of pregnancy. Follow-up of the children (N = 581) was completed when the youngest child reached age 3 years in March 2014. INTERVENTIONS: Vitamin D3 (2400 IU/d; n = 315) or matching placebo tablets (n = 308) from pregnancy week 24 to 1 week postpartum. All women received 400 IU/d of vitamin D3 as part of usual pregnancy care. MAIN OUTCOMES AND MEASURES: Age at onset of persistent wheeze in the first 3 years of life. Secondary outcomes included number of episodes of troublesome lung symptoms, asthma, respiratory tract infections, and neonatal airway immunology. Adverse events were assessed. RESULTS: Of the 581 children, persistent wheeze was diagnosed during the first 3 years of life in 47 children (16%) in the vitamin D3 group and 57 children (20%) in the control group. Vitamin D3 supplementation was not associated with the risk of persistent wheeze, but the number of episodes of troublesome lung symptoms was reduced, and the airway immune profile was up-regulated (principal component analysis, P = .04). There was no effect on additional end points. Intrauterine death was observed in 1 fetus (<1%) in the vitamin D3 group vs 3 fetuses (1%) in the control group and congenital malformations in 17 neonates (5%) in the vitamin D3 group vs 23 neonates (8%) in the control group. [table: see text]. CONCLUSIONS AND RELEVANCE: The use of 2800 IU/d of vitamin D3 during the third trimester of pregnancy compared with 400 IU/d did not result in a statistically significant reduced risk of persistent wheeze in the offspring through age 3 years. However, interpretation of the study is limited by a wide CI that includes a clinically important protective effect. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00856947. PMID- 26813209 TI - Effect of Prenatal Supplementation With Vitamin D on Asthma or Recurrent Wheezing in Offspring by Age 3 Years: The VDAART Randomized Clinical Trial. AB - IMPORTANCE: Asthma and wheezing begin early in life, and prenatal vitamin D deficiency has been variably associated with these disorders in offspring. OBJECTIVE: To determine whether prenatal vitamin D (cholecalciferol) supplementation can prevent asthma or recurrent wheeze in early childhood. DESIGN, SETTING, AND PARTICIPANTS: The Vitamin D Antenatal Asthma Reduction Trial was a randomized, double-blind, placebo-controlled trial conducted in 3 centers across the United States. Enrollment began in October 2009 and completed follow up in January 2015. Eight hundred eighty-one pregnant women between the ages of 18 and 39 years at high risk of having children with asthma were randomized at 10 to 18 weeks' gestation. Five participants were deemed ineligible shortly after randomization and were discontinued. INTERVENTIONS: Four hundred forty women were randomized to receive daily 4000 IU vitamin D plus a prenatal vitamin containing 400 IU vitamin D, and 436 women were randomized to receive a placebo plus a prenatal vitamin containing 400 IU vitamin D. MAIN OUTCOMES AND MEASURES: Coprimary outcomes of (1) parental report of physician-diagnosed asthma or recurrent wheezing through 3 years of age and (2) third trimester maternal 25 hydroxyvitamin D levels. RESULTS: Eight hundred ten infants were born in the study, and 806 were included in the analyses for the 3-year outcomes. Two hundred eighteen children developed asthma or recurrent wheeze: 98 of 405 (24.3%; 95% CI, 18.7%-28.5%) in the 4400-IU group vs 120 of 401 (30.4%, 95% CI, 25.7%-73.1%) in the 400-IU group (hazard ratio, 0.8; 95% CI, 0.6-1.0; P = .051). Of the women in the 4400-IU group whose blood levels were checked, 289 (74.9%) had 25 hydroxyvitamin D levels of 30 ng/mL or higher by the third trimester of pregnancy compared with 133 of 391 (34.0%) in the 400-IU group (difference, 40.9%; 95% CI, 34.2%-47.5%, P < .001). CONCLUSIONS AND RELEVANCE: In pregnant women at risk of having a child with asthma, supplementation with 4400 IU/d of vitamin D compared with 400 IU/d significantly increased vitamin D levels in the women. The incidence of asthma and recurrent wheezing in their children at age 3 years was lower by 6.1%, but this did not meet statistical significance; however, the study may have been underpowered. Longer follow-up of the children is ongoing to determine whether the difference is clinically important. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00920621. PMID- 26813210 TI - Effects of Nicotine Patch vs Varenicline vs Combination Nicotine Replacement Therapy on Smoking Cessation at 26 Weeks: A Randomized Clinical Trial. AB - IMPORTANCE: Smoking cessation medications are routinely used in health care; it is vital to identify medications that most effectively treat this leading cause of preventable mortality. OBJECTIVE: To compare the efficacies of varenicline, combination nicotine replacement therapy (C-NRT), and the nicotine patch for 26 week quit rates. DESIGN, SETTING, AND PARTICIPANTS: Three-group randomized intention-to-treat clinical trial occurring from May 2012 to November 2015 among smokers recruited in the Madison, Wisconsin, and Milwaukee, Wisconsin, communities; 65.5% of smokers offered the study (2687/4102) refused participation prior to randomization. INTERVENTIONS: Participants were randomized to one of three 12-week open-label smoking cessation pharmacotherapy groups: (1) nicotine patch only (n = 241); (2) varenicline only (including 1 prequit week; n = 424); and (3) C-NRT (nicotine patch + nicotine lozenge; n = 421). Six counseling sessions were offered. MAIN OUTCOMES AND MEASURES: The primary outcome was carbon monoxide-confirmed self-reported 7-day point-prevalence abstinence at 26 weeks. Secondary outcomes were carbon monoxide-confirmed self-reported initial abstinence, prolonged abstinence at 26 weeks, and point-prevalence abstinence at weeks 4, 12, and 52. RESULTS: Among 1086 smokers randomized (52% women; 67% white; mean age, 48 years; mean of 17 cigarettes smoked per day), 917 (84%) provided 12-month follow-up data. Treatments did not differ on any abstinence outcome measure at 26 or 52 weeks, including point-prevalence abstinence at 26 weeks (nicotine patch, 22.8% [55/241]; varenicline, 23.6% [100/424]; and C-NRT, 26.8% [113/421]) or at 52 weeks (nicotine patch, 20.8% [50/241]; varenicline, 19.1% [81/424]; and C-NRT, 20.2% [85/421]). At 26 weeks, the risk differences for abstinence were, for patch vs varenicline, -0.76% (95% CI, -7.4% to 5.9%); for patch vs C-NRT, -4.0% (95% CI, -10.8% to 2.8%); and for varenicline vs C-NRT, 3.3% (95% CI, -9.1% to 2.6%). All medications were well tolerated, but varenicline produced more frequent adverse events than did the nicotine patch for vivid dreams, insomnia, nausea, constipation, sleepiness, and indigestion. CONCLUSIONS AND RELEVANCE: Among adults motivated to quit smoking, 12 weeks of open-label treatment with nicotine patch, varenicline, or C-NRT produced no significant differences in biochemically confirmed rates of smoking abstinence at 26 weeks. The results raise questions about the relative effectiveness of intense smoking pharmacotherapies. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01553084. PMID- 26813211 TI - Screening for Depression in Adults: US Preventive Services Task Force Recommendation Statement. AB - DESCRIPTION: Update of the 2009 US Preventive Services Task Force (USPSTF) recommendation on screening for depression in adults. METHODS: The USPSTF reviewed the evidence on the benefits and harms of screening for depression in adult populations, including older adults and pregnant and postpartum women; the accuracy of depression screening instruments; and the benefits and harms of depression treatment in these populations. POPULATION: This recommendation applies to adults 18 years and older. RECOMMENDATION: The USPSTF recommends screening for depression in the general adult population, including pregnant and postpartum women. Screening should be implemented with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up. (B recommendation). PMID- 26813213 TI - Analyzing Repeated Measurements Using Mixed Models. PMID- 26813212 TI - Primary Care Screening for and Treatment of Depression in Pregnant and Postpartum Women: Evidence Report and Systematic Review for the US Preventive Services Task Force. AB - IMPORTANCE: Depression is a source of substantial burden for individuals and their families, including women during the pregnant and postpartum period. OBJECTIVE: To systematically review the benefits and harms of depression screening and treatment, and accuracy of selected screening instruments, for pregnant and postpartum women. Evidence for depression screening in adults in general is available in the full report. DATA SOURCES: MEDLINE, PubMed, PsycINFO, and the Cochrane Collaboration Registry of Controlled Trials through January 20, 2015; references; and government websites. STUDY SELECTION: English-language trials of benefits and harms of depression screening, depression treatment in pregnant and postpartum women with screen-detected depression, and diagnostic accuracy studies of depression screening instruments in pregnant and postpartum women. DATA EXTRACTION AND SYNTHESIS: Two investigators independently reviewed abstracts and full-text articles and extracted data from fair- and good-quality studies. Random-effects meta-analysis was used to estimate the benefit of cognitive behavioral therapy (CBT) in pregnant and postpartum women. MAIN OUTCOMES AND MEASURES: Depression remission, prevalence, symptoms, and related measures of depression recovery or response; sensitivity and specificity of selected screening measures to detect depression; and serious adverse effects of antidepressant treatment. RESULTS: Among pregnant and postpartum women 18 years and older, 6 trials (n = 11,869) showed 18% to 59% relative reductions with screening programs, or 2.1% to 9.1% absolute reductions, in the risk of depression at follow-up (3-5 months) after participation in programs involving depression screening, with or without additional treatment components, compared with usual care. Based on 23 studies (n = 5398), a cutoff of 13 on the English language Edinburgh Postnatal Depression Scale demonstrated sensitivity ranging from 0.67 (95% CI, 0.18-0.96) to 1.00 (95% CI, 0.67-1.00) and specificity consistently 0.87 or higher. Data were sparse for Patient Health Questionnaire instruments. Pooled results for the benefit of CBT for pregnant and postpartum women with screen-detected depression showed an increase in the likelihood of remission (pooled relative risk, 1.34 [95% CI, 1.19-1.50]; No. of studies [K] = 10, I2 = 7.9%) compared with usual care, with absolute increases ranging from 6.2% to 34.6%. Observational evidence showed that second-generation antidepressant use during pregnancy may be associated with small increases in the risks of potentially serious harms. CONCLUSIONS AND RELEVANCE: Direct and indirect evidence suggested that screening pregnant and postpartum women for depression may reduce depressive symptoms in women with depression and reduce the prevalence of depression in a given population. Evidence for pregnant women was sparser but was consistent with the evidence for postpartum women regarding the benefits of screening, the benefits of treatment, and screening instrument accuracy. PMID- 26813214 TI - Association of Immunotherapies With Outcomes in Relapsing-Remitting Multiple Sclerosis. AB - CLINICAL QUESTION: What immunotherapies for multiple sclerosis are associated with the greatest benefit and highest risk of discontinuation due to adverse events in patients with relapsing-remitting multiple sclerosis? BOTTOM LINE: Alemtuzumab, natalizumab, and fingolimod were associated with the greatest benefit with regard to relapse prevention. Their association with prevention of disability worsening was unclear. Fingolimod was associated with a high risk of treatment discontinuation due to adverse events. PMID- 26813215 TI - Safety of Propranolol Therapy for Severe Infantile Hemangioma. PMID- 26813216 TI - Physical Activity vs Health Education for Cognition in Sedentary Older Adults. PMID- 26813217 TI - Physical Activity vs Health Education for Cognition in Sedentary Older Adults- Reply. PMID- 26813218 TI - Epinephrine Administration and Pediatric In-Hospital Cardiac Arrest. PMID- 26813219 TI - Marriage Equality Act and Changes to Health Insurance Coverage. PMID- 26813220 TI - Marriage Equality Act and Changes to Health Insurance Coverage--Reply. PMID- 26813221 TI - Epinephrine Administration and Pediatric In-Hospital Cardiac Arrest--Reply. PMID- 26813222 TI - Addition of Missing Covariate. PMID- 26813223 TI - Error in the Text. PMID- 26813225 TI - A Medicolegal Study of Blood Stains. PMID- 26813226 TI - JAMA PATIENT PAGE. Screening for Depression. PMID- 26813227 TI - Effects of Salt Loading on the Morphology of Astrocytes in the Ventral Glia Limitans of the Rat Supraoptic Nucleus. AB - In the ventral glial limitans (VGL) of the supraoptic nucleus (SON) of the rat, a unique astrocyte type is found with an ability to undergo striking morphological plasticity in response to a wide range of physiological stimulations such as chronic hypernatraemia. This includes a thinning of the VGL, which contains the somata and proximal processes of these astrocytes, as well as an almost complete withdrawal of their vertically-oriented distal processes. Currently, there is little information available on the types of astrocytes that reside in the SON VGL and which of these exhibit state-dependent structural plasticity. To address this, we enabled the visualisation of single SON-VGL glia using two novel cell labelling techniques with fluorescence microscopy. First, we used an inducible genetic reporter mouse line that allowed the specific labelling of a low density of astrocytes expressing glutamate and aspartate transporter (GLAST)/excitatory amino acid transporter 1. This approach revealed a high degree of variability in the morphology of mouse SON-VGL astrocytes, in contrast to what has been reported for cortical astrocytes. Next, we used the DiOlistlic labelling approach to label single glial cells with DiI in the SON-VGL of rats. Astrocytes observed using this approach shared the morphological features of GLAST-expressing astrocytes in the mouse SON-VGL. Specific structural aspects of these cells were modified by chronic hypernatraemia achieved by 7-day salt loading. Notably, the average area of cells exhibiting protoplasmic features was significantly reduced in the horizontal plane, and the size of varicosities present on fibrous projections was significantly enlarged. These observations indicate that novel cell labelling methods can significantly advance our understanding of SON-VGL cells and reveal specific forms of morphological plasticity that can be driven by chronic hypernatraemia. PMID- 26813228 TI - A New Era for Lipids: Introduction of Rapid Communications. PMID- 26813229 TI - Systematic analysis of design and stratification for phase III trials in first line advanced non-small cell lung cancer. AB - BACKGROUND: A recent study reviewed phase III trials of first-line advanced non small cell lung cancer (NSCLC) conducted from 1981 to 2010, and provided trends in the study outcome. However, such trials have never been analyzed in detail for design and stratification factors. METHODS: Phase III studies of systemic treatment for first-line advanced or metastatic NSCLC published in English literature between 1981 and 2010 were identified. Characteristics, including sample size, number of trials, region, rate of meeting accrual goal, primary endpoint, type of phase III, interim analysis, allocation method, and stratification factors, were determined for each decade. RESULTS: A total of 162 studies met the criteria. The number of studies and sample size increased over the three decades. The primary endpoint was reported more frequently in recent decades, and non-overall survival endpoints were chosen in European and Asian studies. Interim analysis was conducted more commonly during the 2000s. Allocation method was rarely reported throughout the three decades. The number of stratification factors increased significantly from one in 1980s to three in 2000s. Performance status, stage, and institution were most frequently selected, and at least one of the three factors was used in most of the studies in the 2000s. However, there are many other stratification factors that were used infrequently. CONCLUSIONS: Despite Consolidated Standards of Reporting Trials guidelines, allocation method has rarely been reported. The choice of stratification factor remains inconsistent across studies. PMID- 26813230 TI - Evaluation of 968 children with corrosive substance ingestion. AB - BACKGROUND AND AIMS: The aim of the study was to evaluate the etiology, treatment, and prognosis in children who had presented at our clinic with corrosive substance ingestion and comparison of our results with the literature. MATERIALS AND METHODS: The patients were put on nil by mouth and broad-spectrum antibiotics were administered. Oral fluids were started for patients whose intraoral lesions resolved and who could swallow their saliva. Steroids were not given, a nasogastric catheter was not placed, and early endoscopy was not used. RESULTS: A total of 968 children presented at our clinic for corrosive substance ingestion during the 22-year period. The stricture development rate was 13.5%. Alkali substance ingestion caused a stricture development rate of 23%. A total of 54 patients required 1-52 sessions (mean 15 +/-12) of dilatation. CONCLUSION: We do not perform early endoscopy, administer steroids, or place a nasogastric catheter at our clinic for patients who had ingested a corrosive substance. This approach has provided results similar to other series. We feel that determining the burn with early esophagoscopy when factors that prevent or decrease the development of corrosive strictures will be very important. PMID- 26813231 TI - Knowledge, attitudes, and practice of drivers towards traffic regulations in Bandar-Abbas, Iran. AB - INTRODUCTION: Traffic injuries are among the leading causes of death and disability in many countries. The knowledge, attitudes, and practice of drivers towards traffic regulations are key factors in decreasing traffic injuries and deaths. The objectives of this research were to study the knowledge, attitudes, and practice of taxi drivers towards traffic regulations in Bandar-Abbas, Iran, and to determine the relationships between demographic features and knowledge, attitudes, and practice of taxi drivers towards traffic regulations. METHODS: This cross-sectional study was done in 2014 in Bandar-Abbas, Iran (Hormozgan Province). To study the knowledge, attitudes, and practice of 241 intra-city taxi drivers towards traffic regulations, researchers developed questionnaires and a checklist. The chi-squared test was performed to determine the relationships between knowledge, attitude, and practice of drivers towards traffic regulations and demographic features. RESULTS: Among the 241 drivers, 50 of them (20.7%) thought that the seat belt could cause discomfort while driving, and 107 (44.4%) did not wear a seat belt while driving. The study determined that there was a significant difference between the knowledge and work experience of the drivers (p = 0.014). The 94 drivers (43.5%) in the 31-40 year age group had positive attitudes towards traffic regulations (among 216 drivers expressed positive attitudes) and 92 (44.4%) of the drivers in this age group had safe practices towards traffic regulations (among 207 drivers with safe practice). CONCLUSION: Many of the taxi drivers in Bandar-Abbas had inadequate knowledge, less positive attitudes, and risky practices towards traffic regulations. Implementation of effective intervention programs may increase the taxi drivers' knowledge, attitudes, and practices towards traffic regulations. PMID- 26813232 TI - Evaluation of the autogenous bone block transfer for dental implant placement: Symphysal or ramus harvesting? AB - BACKGROUND: The absence of sufficient bone volume is the most relevant problem in implant dentistry. Grafting from exogenous sources may provide a limited gain but exhibits poor performance in large bone defects. Autogenous bone block transfer (ABBT) from the mandibular symphysis and ramus has been used with varying rates of success. The aim of this study was to compare the efficacy of symphysal and ramus ABBT for the restoration of lost horizontal alveolar bone volume in the anterior maxilla. Implants placed in the augmented areas were also evaluated. METHODS: The maxillary alveolar bone deficits of 32 patients were treated by similar-sized autogenous bone blocks (7 * 7 * 4 mm) harvested from the symphysis or ramus area. After 4 to 5 months of healing, implants were inserted. At the end of the osseointegration period, the implants were restored by fixed prostheses. Baseline bone thickness was determined by Cone beam computed tomography and was compared to post-op and one-year post-loading bone thickness values where the implants were inserted. Any complications or consequences were noted. The success and survival of the 45 implants were evaluated. The results were analyzed using the Student t-test and Fisher's exact test (p < 0.05). RESULTS: Post-op complications were frequent in both groups. Baseline bone thickness values were similar at the beginning of the study (p = 0.71) and exhibited a significant increase after the ABBT surgery (6.29 (SD 0.86) and 6.01 (SD 0.92) mm in the symphysis and ramus groups, respectively). The amount of bone thickness gain was 4.34 mm (SD: 0.92) and 4.36 mm (SD: 1.01) in the symphysis and ramus groups, respectively. After one year, the mean surface resorption was 0.6 mm (SD: 0.78) and 0.80 mm (SD: 0.56) for the symphysis and ramus groups, respectively (p = 0.089). The success and survival rates of the implants were 94.11 and 96.42 %, respectively. No graft failures were observed. CONCLUSIONS: Both symphysal and ramus ABBT procedures were successful for the restoration of a horizontal bone defect in the anterior maxilla. Ramus harvesting may be advisable due to fewer complications. Implants placed in the grafted regions exhibited a high success and survival rate within the one-year follow-up period. PMID- 26813234 TI - Use of overlapping buccal mucosa graft urethroplasty for complex anterior urethral strictures. AB - Complex anterior urethral stricture disease typically manifests as a symptomatic, severely narrowed, long stricture (or multiple strictures) in which conventional excision and/or augmentation is not feasible. Overlapping buccal mucosal graft urethroplasty (OBMGU) is an innovative hybrid technique, combining the well established principles of dorsal and ventral graft augmentation to allow single stage reconstruction of complex anterior urethral strictures. In this review, we discuss the rationale, techniques, and outcomes of OBMGU for complex anterior urethral strictures. PMID- 26813235 TI - Agminated eruptive pyogenic granuloma on chin following redundant needle injections. PMID- 26813233 TI - Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients. AB - BACKGROUND: The androgen receptor (AR) is a pivotal drug target for the treatment of prostate cancer, including its lethal castration-resistant (CRPC) form. All current non-steroidal AR antagonists, such as hydroxyflutamide, bicalutamide, and enzalutamide, target the androgen binding site of the receptor, competing with endogenous androgenic steroids. Several AR mutations in this binding site have been associated with poor prognosis and resistance to conventional prostate cancer drugs. In order to develop an effective CRPC therapy, it is crucial to understand the effects of these mutations on the functionality of the AR and its ability to interact with endogenous steroids and conventional AR inhibitors. RESULTS: We previously utilized circulating cell-free DNA (cfDNA) sequencing technology to examine the AR gene for the presence of mutations in CRPC patients. By modifying our sequencing and data analysis approaches, we identify four additional single AR mutations and five mutation combinations associated with CRPC. Importantly, we conduct experimental functionalization of all the AR mutations identified by the current and previous cfDNA sequencing to reveal novel gain-of-function scenarios. Finally, we evaluate the effect of a novel class of AR inhibitors targeting the binding function 3 (BF3) site on the activity of CRPC associated AR mutants. CONCLUSIONS: This work demonstrates the feasibility of a prognostic and/or diagnostic platform combining the direct identification of AR mutants from patients' serum, and the functional characterization of these mutants in order to provide personalized recommendations regarding the best future therapy. PMID- 26813236 TI - The effects of proliferation and DNA damage on hematopoietic stem cell function determine aging. AB - In most of the mammalian tissues, homeostasis as well as injury repair depend upon a small number of resident adult stem cells. The decline in tissue/organ function in aged organisms has been directly linked with poorly functioning stem cells. Altered function of hematopoietic stem cells (HSCs) is at the center of an aging hematopoietic system, a tissue with high cellular turnover. Poorly engrafting, myeloid-biased HSCs with higher levels of DNA damage accumulation are the hallmark features of an aged hematopoietic system. These cells show a higher proliferation rate than their younger counterparts. It was proposed that quiescence of these cells over long period of time leads to accumulation of DNA damage, eventually resulting in poor function/pathological conditions in hematopoietic system. However, various mouse models with premature aging phenotype also show highly proliferative HSCs. This review examines the evidence that links proliferation of HSCs with aging, which leads to functional changes in the hematopoietic system. Developmental Dynamics 245:739-750, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26813237 TI - Effect of phylogenetic diversity of velogenic Newcastle disease virus challenge on virus shedding post homologous and heterologous DNA vaccination in chickens. AB - Newcastle disease (ND) is a highly devastating disease for the poultry industry as it causes high economic losses. In this present study, a DNA vaccine containing the F and HN surface antigens of a highly virulent Newcastle disease virus (NDV), NDV/1/Chicken/2005 (FJ939313), was successfully generated. Cell transfection test indicated that the vaccine expressed the F and HN genes in Hep 2 cells. The main objective of this study was to compare the extent of protection induced by DNA vaccination after homologous and heterologous NDV-challenge as determined by the amount of NDV shedding after challenge. NDV-antibody-negative chickens were vaccinated either once, twice or thrice intramuscularly at 7, 14 and 21 days old and were challenged 14 days post vaccination with either homologous virus (vaccine-matched velogenic viscerotropic Newcastle disease virus (vvNDV) strain, FJ939313), phylogenetically related to group VII, or a phylogenetically divergent heterologous virus (unmatched vvNDV strain, AY968809), which belongs to genogroup VI and shows 84.1% nucleotide similarity to the NDV sequences of the DNA vaccine. Our data indicate that birds, which received a single dose of the DNA vaccine were poorly protected, and only 30-40% of these birds survived after challenge with high virus shedding titre. Multiple administration of the DNA vaccine induced high protection rates of 70-90% with reduced virus shedding compared to the non-vaccinated and challenged birds. Generally, homologous challenge led to reduced tracheal and cloacal shedding compared to the heterologous vvNDV strain. This study provides a promising approach for the control of ND in chickens using DNA vaccines, which are phylogenetically closely related to the circulating field strains. PMID- 26813238 TI - Evaluation of Sexual and Urinary Function After Implementation of Robot-assisted Surgery for Rectal Cancer: A Single-Center Study. AB - PURPOSE: Our objective was to report postoperative urogenital dysfunction after rectal cancer surgery, identifying possible predictors including conventional laparoscopic total mesorectal excision and robot-assisted total mesorectal excision laparoscopic surgery. MATERIALS AND METHODS: Questionnaires were mailed to 184 patients who underwent laparoscopic rectal cancer surgery between January 2009 and May 2013. Single questions were used to retrospectively assess preoperative urogenital dysfunction. Surgical data were collected from hospital records. Postoperative urinary and sexual function was measured with validated questionnaires and the results were statistically analyzed. RESULTS: A total of 97 questionnaires were included in the study. Of those sexually active before the operation, 81% reported some degree of erectile dysfunction (ED). In total, 73% reported some degree of orgasmic dysfunction (OD). On multivariate analyses, older age was the only predictor for ED (P=0.0012). Older age (P=0.007) and having a rectal extirpation procedure (P=0.013) were predictors of OD. CONCLUSIONS: ED and OD are common after rectal cancer surgery. Robotic surgery was seemingly not associated with ED or OD. PMID- 26813239 TI - Adenoma Detection Rate in Colonoscopy: Is Indication a Predictor? AB - PURPOSE: To describe factors that may influence adenoma detection rate (ADR), with an emphasis on the indication for colonoscopy. METHODS: Consecutive colonoscopies performed by a single endoscopist between January 2008 and December 2014 were reviewed. Indications for colonoscopy were tested for association with ADR after adjusting for age and sex. RESULTS: A total of 2648 colonoscopies were analyzed. Adenomas were detected in 630 patients (23.8%). Overall ADR was 22.9% in patients undergoing screening colonoscopy. ADR was higher in fecal occult blood test-triggered screening colonoscopies (32%) than colonoscopies performed for patients with a family history of colorectal cancer (21.7%) or asymptomatic average-risk individuals (20.4%) (P=0.05). ADR was 36.1% in patients undergoing surveillance colonoscopy and ranged from 12% to 30% in patients with gastrointestinal symptoms undergoing diagnostic colonoscopy. CONCLUSIONS: ADR differs depending on whether the indication is screening, surveillance, or diagnosis. Within screening colonoscopies, ADR seems to be higher in patients with a positive fecal occult blood test. PMID- 26813240 TI - The Novel Transvestibule Approach for Endoscopic Thyroidectomy: A Case Series. AB - OBJECT: To evaluate the feasibility of NOTES for thyroid by the transvestibule approach. METHODS: Six patients diagnosed with benign thyroid diseases were enrolled and underwent transvestibule endoscopic thyroidectomy in our hospital from October 2013 to September 2014. RESULTS: All 6 patients completed transvestibule endoscopic thyroidectomy successfully with no conversion to open surgery. The mean operation time was 122 minutes (100 to 150 min). The average blood loss during surgery was 30 mL (10 to 40 mL). The pathologic diagnosis coincided with the preoperative diagnosis, which was 1 case of thyroid adenoma and 5 cases of thyroid goiters. The mean length of hospital stay was 8.2 days (8 to 10 d). No severe complications were reported during the 3 to 13 months' follow up. CONCLUSIONS: Transvestibule endoscopic thyroidectomy is feasible, with a satisfactory cosmetic effect; yet, further improvement of surgical techniques are required on account of the complexity of the surgical procedure and the prolonged operation time. PMID- 26813241 TI - Early Improvements in Individual Symptoms to Predict Later Remission in Major Depressive Disorder Treated With Mirtazapine. AB - Few studies, to our knowledge, have examined whether early improvements in individual, instead of overall, depressive symptoms predict remission in major depressive disorder (MDD). This post hoc analysis used data from 194 patients with MDD enrolled in a 6-week double-blind, placebo-controlled, randomized trial of mirtazapine, to identify improvements in specific individual depressive symptoms in the early phase that are associated with subsequent remission. Trajectories of individual depressive symptoms over 6 weeks were compared between remitters and nonremitters. Early improvement was defined as a >=20% decrease in the Hamilton Rating Scale for Depression 17 items (HAM-D17) total score in weeks 1 and 2, and remission was defined as a HAM-D17 final score of <=7. Reliability parameters were calculated for early improvements in predicting later remission. Whether improvement in each of the HAM-D17 symptoms in weeks 1 or 2 predicted remission was examined, using binary logistic regression analyses. As a result, improvements in weeks 1 and 2 were associated with sensitivity of 0.82 and 0.99 and specificity of 0.54 and 0.44, respectively, in predicting remission in week 6. Improvements in insomnia late (P = .04) and insight (P = .007) in week 1 and somatic symptoms general (P = .002) and insight (P = .04) in week 2 were associated with remission in week 6. In conclusion, early improvements in insight, insomnia late, and somatic symptoms general, as well as overall depressive symptoms, may serve as specific clinical indicators of subsequent remission in patients with MDD receiving mirtazapine. PMID- 26813242 TI - Implant-retained prostheses: ball vs. conus attachments - A randomized controlled clinical trial. AB - OBJECTIVE: To evaluate implant survival, peri-implant tissue conditions, prosthodontic maintenance requirements and patient satisfaction of two differently retained implant-supported mandibular overdentures (IOD) after the 3 years of observation. MATERIALS AND METHODS: Twenty-five patients with edentulous mandibles received two implants each. Twelve patients were randomly selected to receive ball attachments, whereas 13 patients received prefabricated coni. Implant survival, peri-implant parameters (modified Plaque Index, Bleeding on Probing, modified Gingival Index, probing depth and marginal bone loss) and patient satisfaction were assessed. Additionally, prosthodontic maintenance was monitored. Clinical and radiographic follow-ups were performed 1, 2 and 3 years after prosthetic delivery. The Kaplan-Meier method was used to calculate complication rates. RESULTS: After a mean observation period of 29.6 months, an implant survival rate of 100% could be observed. There were no significant differences in the peri-implant parameters. During the observation period, six patients with conus attachment refused to further participate in follow-ups due to dissatisfaction with their treatment and had to be regarded as dropouts. Based on the Kaplan-Meier method, inacceptable retention was calculated for 80% and 75% of the patients in the ball and the conus groups, respectively. Patient satisfaction was 64% for the ball- and 100% for the conus-retained IODs, the latter only respecting five of initially 13 patients. CONCLUSION: The evaluated treatment method revealed high implant survival rates, but the prosthetic reconstruction required intensive maintenance. Therefore, a trend toward the reduced patient satisfaction was observed, and the promoted economy of the evaluated attachment systems should be questioned. For the conical attachment, the recommendation of the manufacturer is to use four interforaminal implants to support a removable prostheses. PMID- 26813243 TI - The Influence of Apical Aneurysm on Left Ventricular Geometry and Clinical Outcomes: 3-Year Follow-Up Using Echocardiography. AB - BACKGROUND: Left ventricular apical aneurysm (LVAA) is a serious complication associated with myocardial infarction. However, the effects of a previously formed LVAA on long-term left ventricular (LV) geometry and clinical outcomes have not been fully evaluated. METHODS: From January 2009 to May 2015, we retrospectively identified 70 patients (mean age, 66 +/- 12 years; males, 72.9%) with an LVAA due to ischemia. These patients were classified into two groups according to the initial apical conicity ratio (ACR): large LVAA group (ACR >= 1.5, n = 40) and small LVAA group (ACR < 1.5, n = 30). An adverse outcome was defined as a composite of fatal arrhythmia, embolic infarction, and readmission due to heart failure. RESULTS: The ACR significantly decreased over the first month and then increased after 1 and 3 years of follow-up. The other examined echocardiographic indexes did not exhibit temporal changes. During the follow-up period (median 1138 days), the large LVAA group experienced a lower event-free survival (P = 0.016). In a multivariate Cox model, the presence of a large LVAA (adjusted hazard ratio [HR] = 2.795, 95% confidence interval [CI] = 1.118-6.986, P = 0.028) and the initial LV ejection fraction (EF) (adjusted HR = 0.964, 95% CI = 0.932-0.997, P = 0.034) were independent predictors of adverse outcomes. CONCLUSIONS: This study demonstrates that LVAAs undergo a dynamic process and that large LVAAs are associated with adverse outcomes. Our results suggest that the ACR could be helpful for predicting adverse outcomes in patients with apical aneurysm. PMID- 26813244 TI - A microbial carbonate response in synchrony with the end-Triassic mass extinction across the SW UK. AB - The eruption of the Central Atlantic Magmatic Province (CAMP)-the largest igneous province known-has been linked to the end-Triassic mass extinction event, however reconciling the response of the biosphere (at local and nonlocal scales) to potential CAMP-induced geochemical excursions has remained challenging. Here we present a combined sedimentary and biological response to an ecosystem collapse in Triassic-Jurassic strata of the southwest United Kingdom (SW UK) expressed as widely distributed carbonate microbialites and associated biogeochemical facies. The microbialites (1) occur at the same stratigraphic level as the mass extinction extinction, (2) host a negative isotope excursion in delta(13)Corg found in other successions around the world, and (3) co-occur with an acme of prasinophyte algae 'disaster taxa' also dominant in Triassic-Jurassic boundary strata of other European sections. Although the duration of microbialite deposition is uncertain, it is likely that they formed rapidly (perhaps fewer than ten thousand years), thus providing a high-resolution glimpse into the initial carbon isotopic perturbation coincident with the end-Triassic mass extinction. These findings indicate microbialites from the SW UK capture a nonlocal biosedimentary response to the cascading effects of massive volcanism and add to the current understanding of paleoecology in the aftermath of the end Triassic extinction. PMID- 26813245 TI - The Innovator. PMID- 26813246 TI - Driving change in population health. PMID- 26813247 TI - An inquiry about the theoretical and philosophical frameworks used in "a practical field guide to conducting nursing research in low-and middle-income countries". PMID- 26813248 TI - Investing in nursing and midwifery enterprise to empower women and strengthen health services and systems: An emerging global body of work. AB - In September of 2014, the Institute of Medicine (IOM) convened a global Rockefeller Bellagio Center workshop focusing on the largely overlooked area of investment in nursing and midwifery enterprise as a means for both empowering women and strengthening health systems and services. The report of this meeting, Empowering Women and Strengthening Health Systems and Services Through Investing in Nursing and Midwifery Enterprise: Lessons from Lower-Income Countries: Workshop Summary, was released in February, 2015. This report represents a pivotal point in a growing body of work begun in 2012, providing insights and perspectives of global experts that have resulted in subsequent global discussions and are paving the way for the future. This three-part article summarizes the initial exploration leading to the IOM workshop and report, followed by highlights and insights from the report and related meetings, and authors concluding discussion of implications for the future and next steps. PMID- 26813249 TI - Seizures as presenting and prominent symptom in chorea-acanthocytosis with c.2343del VPS13A gene mutation. AB - OBJECTIVE: The aim of the study was to characterize the clinical features of nine patients in three families with chorea-acanthocytosis (ChAc) sharing the same rare c.2343del mutation in the VPS13A gene. METHODS: Genetic test results, clinical description, magnetic resonance imaging (MRI), and electroencephalography (EEG), as well as laboratory results are summarized. RESULTS: ChAc is a rare genetic disorder characterized by hyperkinetic movements, seizures, cognitive decline, neuropsychiatric symptoms, and acanthocytes on peripheral blood smear. This unique cohort of nine patients is characterized by seizures as a first and prominent symptom. In our patients, other features of ChAc appeared later, including tics, other movement disorders, dysarthria, and mild to moderate cognitive decline. SIGNIFICANCE: Patients with chorea acanthocytosis carrying the described rare mutation can present with focal, treatment-resistant seizures. PMID- 26813252 TI - Reconfigurable Optical Signal Processing Based on a Distributed Feedback Semiconductor Optical Amplifier. AB - All-optical signal processing has been considered a solution to overcome the bandwidth and speed limitations imposed by conventional electronic-based systems. Over the last few years, an impressive range of all-optical signal processors have been proposed, but few of them come with reconfigurability, a feature highly needed for practical signal processing applications. Here we propose and experimentally demonstrate an analog optical signal processor based on a phase shifted distributed feedback semiconductor optical amplifier (DFB-SOA) and an optical filter. The proposed analog optical signal processor can be reconfigured to perform signal processing functions including ordinary differential equation solving and temporal intensity differentiation. The reconfigurability is achieved by controlling the injection currents. Our demonstration provitdes a simple and effective solution for all-optical signal processing and computing. PMID- 26813250 TI - One ring to rule them all: Current trends in combating bacterial resistance to the beta-lactams. AB - From humble beginnings of a contaminated petri dish, beta-lactam antibiotics have distinguished themselves among some of the most powerful drugs in human history. The devastating effects of antibiotic resistance have nevertheless led to an "arms race" with disquieting prospects. The emergence of multidrug resistant bacteria threatens an ever-dwindling antibiotic arsenal, calling for new discovery, rediscovery, and innovation in beta-lactam research. Here the current state of beta-lactam antibiotics from a structural perspective was reviewed. PMID- 26813253 TI - Outcomes of Endovascular Aortic Aneurysm Repair in Kidney Transplant Recipients: Results From a National Quality Initiative. AB - Contrast-induced nephropathy after endovascular aortic aneurysm repair (EVAR) in kidney transplant recipients (KTRs) can have devastating consequences. The Vascular Quality Initiative (VQI) database was queried to select all KTRs who underwent EVAR between January 2003 and December 2014. Our primary outcome was renal dysfunction, defined as acute kidney injury (AKI; elevation of serum creatinine >0.5 mg/dL from baseline) or new postoperative hemodialysis requirement. Within the EVAR VQI dataset, 40 patients were KTRs (40 of 17 213, or 0.2%). Renal dysfunction occurred in five of 40 patients in the KTR group in comparison to 779 of 17 173 patients in the nontransplanted group (12.5% versus 4.5%, p < 0.01). Emergent EVAR was required in 2 (5%) patients, one of whom required dialysis after surgery and subsequently died. One-year survival after EVAR was similar in the two groups (92.9% versus 93.1%, p = 0.73). KTRs who developed renal dysfunction had significantly lower preoperative estimated glomerular filtration rates (eGFRs) (29.5 versus 54.7, p = 0.007) and a significantly higher iodine:eGFR ratio (0.78 versus 0.39, p = 0.02) despite receiving a similar volume of contrast (70.0 versus 68.8, p = 0.97). Renal dysfunction is 3 times more frequent in KTRs treated with EVAR, though overall survival did not differ between the groups. Decreased preoperative eGFR and a higher iodine:eGFR ratio are associated with postoperative renal dysfunction. PMID- 26813255 TI - Trends in Global Assisted Reproductive Technologies Research: a Scientometrics study. AB - INTRODUCTION: This study illustrated the global contribution to assisted reproductive technologies (ARTs) research in MEDLINE database from 1998 to 2014. METHODS: In March 2015, the MEDLINE database was searched for research publications indexed under 'reproductive techniques, assisted' (including the following MeSH headings: in vitro fertilization [IVF]; intracytoplasmic sperm injections; cryopreservation; and ovulation induction), with the following expressions in the fields of title or abstract: intrauterine insemination; sperm donation; embryo/egg donation and surrogate mothers. The number of publications in MEDLINE database was recorded for each individual year, 1998-2014, and for each country. The following countries were arbitrarily selected for data retrieval: United States, United Kingdom, France, Germany, Canada, Italy, Japan (G7 countries), Brazil, Russia, India, China (BRIC countries), Egypt, Turkey, Israel and Iran. RESULTS: The absolute number of publications for each country from 1998 to 2014 ranged from 75 to 16453, with a median of 2024. The top five countries were the US (16453 publications), the UK (5427 publications), Japan (4805), China (4660) and France (3795). ART (20277), cryopreservation (11623) and IVF (11209) were the most researched areas. CONCLUSION: Global research on ARTs were geographically distributed and highly concentrated among the world's richest countries. Cryopreservation and IVF were the most productive research domains among ARTs. PMID- 26813254 TI - PAX4 preserves endoplasmic reticulum integrity preventing beta cell degeneration in a mouse model of type 1 diabetes mellitus. AB - AIMS/HYPOTHESIS: A strategy to enhance pancreatic islet functional beta cell mass (BCM) while restraining inflammation, through the manipulation of molecular and cellular targets, would provide a means to counteract the deteriorating glycaemic control associated with diabetes mellitus. The aims of the current study were to investigate the therapeutic potential of such a target, the islet-enriched and diabetes-linked transcription factor paired box 4 (PAX4), to restrain experimental autoimmune diabetes (EAD) in the RIP-B7.1 mouse model background and to characterise putative cellular mechanisms associated with preserved BCM. METHODS: Two groups of RIP-B7.1 mice were genetically engineered to: (1) conditionally express either PAX4 (BPTL) or its diabetes-linked mutant variant R129W (mutBPTL) using doxycycline (DOX); and (2) constitutively express luciferase in beta cells through the use of RIP. Mice were treated or not with DOX, and EAD was induced by immunisation with a murine preproinsulin II cDNA expression plasmid. The development of hyperglycaemia was monitored for up to 4 weeks following immunisation and alterations in the BCM were assessed weekly by non-invasive in vivo bioluminescence intensity (BLI). In parallel, BCM, islet cell proliferation and apoptosis were evaluated by immunocytochemistry. Alterations in PAX4- and PAX4R129W-mediated islet gene expression were investigated by microarray profiling. PAX4 preservation of endoplasmic reticulum (ER) homeostasis was assessed using thapsigargin, electron microscopy and intracellular calcium measurements. RESULTS: PAX4 overexpression blunted EAD, whereas the diabetes-linked mutant variant PAX4R129W did not convey protection. PAX4-expressing islets exhibited reduced insulitis and decreased beta cell apoptosis, correlating with diminished DNA damage and increased islet cell proliferation. Microarray profiling revealed that PAX4 but not PAX4R129W targeted expression of genes implicated in cell cycle and ER homeostasis. Consistent with the latter, islets overexpressing PAX4 were protected against thapsigargin mediated ER-stress-related apoptosis. Luminal swelling associated with ER stress induced by thapsigargin was rescued in PAX4-overexpressing beta cells, correlating with preserved cytosolic calcium oscillations in response to glucose. In contrast, RNA interference mediated repression of PAX4-sensitised MIN6 cells to thapsigargin cell death. CONCLUSIONS/INTERPRETATION: The coordinated regulation of distinct cellular pathways particularly related to ER homeostasis by PAX4 not achieved by the mutant variant PAX4R129W alleviates beta cell degeneration and protects against diabetes mellitus. The raw data for the RNA microarray described herein are accessible in the Gene Expression Omnibus database under accession number GSE62846. PMID- 26813256 TI - Epidemiology of urethral strictures. AB - Urethral stricture disease is relatively common and is associated with a significant financial cost and potentially debilitating outcomes. Understanding urethral stricture epidemiology is important to identify risk factors associated with the etiology or progression of the disease. This understanding may lead to better treatments and preventative measures that could ameliorate disease severity, produce better health outcomes, and reduce expenditures. We performed a comprehensive review of urethral stricture disease based on available published case series, identified gaps in knowledge of this disease, and recommend future directions for research. PMID- 26813257 TI - Direct growth of single-crystalline III-V semiconductors on amorphous substrates. AB - The III-V compound semiconductors exhibit superb electronic and optoelectronic properties. Traditionally, closely lattice-matched epitaxial substrates have been required for the growth of high-quality single-crystal III-V thin films and patterned microstructures. To remove this materials constraint, here we introduce a growth mode that enables direct writing of single-crystalline III-V's on amorphous substrates, thus further expanding their utility for various applications. The process utilizes templated liquid-phase crystal growth that results in user-tunable, patterned micro and nanostructures of single-crystalline III-V's of up to tens of micrometres in lateral dimensions. InP is chosen as a model material system owing to its technological importance. The patterned InP single crystals are configured as high-performance transistors and photodetectors directly on amorphous SiO2 growth substrates, with performance matching state-of the-art epitaxially grown devices. The work presents an important advance towards universal integration of III-V's on application-specific substrates by direct growth. PMID- 26813259 TI - Hypovolemic shock following induced abortion and spontaneous heterotopic pregnancy. AB - Spontaneous heterotopic pregnancy is a rare clinical condition in which intrauterine and extrauterine pregnancies occur at the same time. It is rare, estimated to occur in 1 in 30,000 pregnancies. The case was a 38-year-old woman with spontaneously conceived heterotopic pregnancy. She was admitted to our center with hypovolemic shock. Focused assessment sonography for trauma examination in emergency department showed large amount of free fluid in peritoneal cavity. She was managed surgical laparotomy. Considering spontaneous pregnancies, physician should be aware of the possibility of heterotopic pregnancy in all reproductive age women, especially those with history of recent abortion. It can occur without any predisposing risk factors. Patients should be informed about possible side effects of nonprescription medicines, and also the health care centers must be safe peaceful environment for them without severe legal consequences. PMID- 26813258 TI - High-fidelity of non-small cell lung cancer xenograft models derived from bronchoscopy-guided biopsies. AB - BACKGROUND: At present, there are two main types of lung cancer xenograft models: those derived from stable cell lines, and patient-derived xenograft models established by surgically resected tissues. However, these animal models may not reflect the biological and genetic characteristics of advanced non-small cell lung cancer (NSCLC). We utilized bronchoscopy-guided biopsy tissues of NSCLC patients to establish xenograft models and analyzed their histopathologic and genotypic fidelity with parental tumors. METHODS: Tumor tissues of NSCLC patients taken via bronchoscope were subcutaneously implanted into mice with non-obese diabetic-severe combined immunodeficiency disease for model establishment and serial passage. The histopathology and genotype of the samples from bronchoscopy guided biopsy-derived xenograft (BDX) models and their parental tumors were detected. RESULTS: Thirty BDXs out of 114 NSCLC patients (26.32%) were successfully established. Smoking status significantly affected the success rate of NSCLC BDX establishment (P = 0.010). The BDX establishment success rate in squamous cell cancer was higher than in adenocarcinoma, with no significant difference (32.00% vs. 16.21%, P = 0.112). However, the growth rate of passage 1 BDX was slower than that of passages 2 and 3. Almost all NSCLC BDXs maintained similarity to their parental tumor tissues in regard to histologic characteristics, pathological markers, and driver-gene mutations. Only one BDX model lost the epidermal growth factor receptor mutation contained in tumor parental tissue, as a result of heterogeneity. CONCLUSIONS: NSCLC BDXs maintained high fidelity of histopathology and genotype with their original tumors. NSCLC BDXs that possess the actual status of advanced lung carcinoma should be used in preclinical research. PMID- 26813260 TI - New frontiers in urethral reconstruction: injectables and alternative grafts. AB - Contemporary management of anterior urethral strictures requires both endoscopic as well as complex substitution urethroplasty, depending on the nature of the urethral stricture. Recent clinical and experimental studies have explored the possibility of augmenting traditional endoscopic urethral stricture management with anti-fibrotic injectable medications. Additionally, although buccal mucosa remains the gold standard graft for substitution urethroplasty, alternative grafts are necessary for reconstructing particularly complex urethral strictures in which there is insufficient buccal mucosa or in cases where it may be contraindicated. This review summarizes the data of the most promising injectable adjuncts to endoscopic stricture management and explores the alternative grafts available for reconstructing the most challenging urethral strictures. Further research is needed to define which injectable medications and alternative grafts may be best suited for urethral reconstruction in the future. PMID- 26813261 TI - A study of an influenza A (H1N1)pdm09 outbreak in pregnant women in Rajasthan, India. AB - OBJECTIVES: To describe the clinical and epidemiological factors of influenza A (H1N1)pdm09-infected patients who were pregnant or in the puerperal period during a recent influenza outbreak in Rajasthan, India. METHODS: A retrospective, observational study was performed using hospital records of individuals with confirmed influenza A (H1N1)pdm09 infection admitted to a large tertiary care center in Rajasthan, India, between January 1 and March 15, 2015. RESULTS: The study cohort included 44 patients who were pregnant or in the puerperal period. The mean age was significantly lower in the study cohort than in other female patients treated for influenza A (H1N1)pdm09 infection at the hospital during the study period (25.45+/-3.45years vs 40.46+/-13.99 years; P<0.001). Mortality was significantly higher in the study cohort than in the comparison female patients (36% vs 17%; P=0.003). Factors found to be associated with mortality were delayed initiation of oseltamivir, poor oxygen saturation at admission, and more than 50% lung involvement under radiographic examination. None of the patients in the study cohort had received a vaccination against seasonal influenza. CONCLUSION: Influenza A (H1N1)pdm09 infection during pregnancy causes more severe illness. Early recognition and timely administration of antiviral therapy can improve outcomes. The role of influenza vaccination in this high-risk population cannot be overemphasized. PMID- 26813262 TI - The Short- and Long-Term Effects of Psychobehavioral Correlates in Buffering Diabetes-Related Cognitive Decline. AB - BACKGROUND/PURPOSE: The short- and long-term impacts of behavioral and psychological factors on the diabetes and cognitive function relationship are not fully understood. This study examined levels and rates of change in age trajectories of cognitive function in middle-aged and older adults with and without diabetes who participated in different health behaviors. METHODS: Participants aged 53 and above with and without diabetes were drawn from the 1999 Taiwan Longitudinal Study of Aging (N = 4076, mean age 69.3, SD = 9.1). Cognitive function was measured with the 9-item Short Portable Mental Status Questionnaire (SPMSQ) in 1999, 2003, and 2007. Lifestyle and psychosocial variables were measured in 1996, 1999, and 2003 as lagged time-varying covariates in random effects model analyses. RESULTS: Adults with diabetes had significantly lower levels of (betadiabetes = -.212, p < .001) cognitive function, compared to those without diabetes, net of the effects of key sociodemographic and comorbidity covariates. The addition of exercise, social support, and depressive symptoms to the analytic models reduced the diabetes impact to non-significance. Exercise alone explained 33 % of the variation in the age trajectory. Only diet behavior showed a significant interaction effect with age (betadiet*age = .011, p < .05). CONCLUSIONS: This population-based longitudinal study provides evidence for the prospective effects of psychobehavioral factors in preserving cognitive function for at least 3 to 4 years in adults with or without diabetes, a result supporting psychoneuroendocrinology studies linking stress and stress hormones to cognitive function, potentially informing treatment options for diabetes care. PMID- 26813263 TI - An Ethogram to Quantify Operating Room Behavior. AB - BACKGROUND: The operating room (OR) is a highly social and hierarchical setting where interprofessional team members must work interdependently under pressure. Due primarily to methodological challenges, the social and behavioral sciences have had trouble offering insight into OR dynamics. PURPOSE: We adopted a method from the field of ethology for observing and quantifying the interpersonal interactions of OR team members. METHODS: We created and refined an ethogram, a catalog of all our subjects' observable social behaviors. The ethogram was then assessed for its feasibility and interobserver reliability. RESULTS: It was feasible to use an ethogram to gather data in the OR. The high interobserver reliability (Cohen's Kappa coefficients of 81 % and higher) indicates its utility for yielding largely objective, descriptive, quantitative data on OR behavior. CONCLUSIONS: The method we propose has potential for social research conducted in healthcare settings as complex as the OR. PMID- 26813264 TI - Chronic Pain Status, Nicotine Withdrawal, and Expectancies for Smoking Cessation Among Lighter Smokers. AB - BACKGROUND: Chronic pain and tobacco smoking are both highly prevalent and comorbid conditions, and chronic pain may pose a barrier to smoking cessation. PURPOSE: The objective of this study was to test associations between chronic pain status and several smoking-related factors that have previously been shown to predict cessation outcomes. METHOD: Daily smokers (N = 205) were recruited from the general population to complete an online survey of pain and tobacco smoking. RESULTS: Results indicated that smokers with chronic pain (vs. no chronic pain) consumed more cigarettes per day, scored higher on an established measure of tobacco dependence, reported having less confidence in their ability to quit, and endorsed expectations for experiencing greater difficulty and more severe nicotine withdrawal during future cessation attempts. Mediation analyses further indicated that the inverse association between chronic pain and abstinence self-efficacy was indirectly influenced by past cessation failures. CONCLUSIONS: These findings suggest that individuals with chronic pain may constitute an important subgroup of tobacco smokers who tend to experience lower confidence and greater difficulty when attempting to quit. Future research would benefit from replicating these findings among older and more diverse samples of heavier tobacco smokers, and extending this work to the study of prospective relations between chronic pain status and cessation-relevant processes/outcomes over the course of a quit attempt. PMID- 26813265 TI - Exemestane-induced radiation recall dermatitis and morbilliform rash. PMID- 26813266 TI - Evaluation of the pylorus with concurrent intraluminal pressure and EndoFLIP in patients with nausea and vomiting. AB - BACKGROUND: Nausea and vomiting occurs in gastroparesis due to diabetes mellitus or unknown causes. The aim of this study was to compare (i) pyloric distensibility to pyloric manometric pressure in patients with nausea and vomiting and (ii) to correlate distensibility with delays in gastric emptying. METHODS: Sleeve manometry and EndoFLIP were performed sequentially during the same endoscopy on 114 patients with nausea and vomiting (47 with diabetes mellitus and 67 with idiopathic cause) after a standardized gastric emptying study. The sleeve manometer was positioned fluoroscopically, and the EndoFLIP was placed endoscopically. Manometric pressure using a water-perfused catheter and distensibility using an EndoFLIP filled with 40 cc of saline were measured from the pylorus. KEY RESULTS: The basal pyloric pressure was elevated (>10 mmHg) in 34 patients and was normal in 80 patients. The basal and peak pressures were similar in patient with normal and delayed gastric emptying (p > 0.05). There was a significant decrease in distensibility (8.0 +/- 1.0 mm(2) /mmHg) in patients with gastric retention (>20% at 4 h) compared with patients (12.4 +/- 1.4 mm(2) /mmHg) (p < 0.01) with normal gastric retention (<10%). Pressure measurements from the sleeve manometer and the EndoFLIP correlated (r = 0.29) (p < 0.002), and increased EndoFLIP balloon pressure (19.4 +/- 1.4 mmHg) (p < 0.01) was associated with a severe delay in gastric emptying. CONCLUSIONS & INFERENCES: Elevated basal pyloric pressure occurs in 42% of patients with nausea and vomiting and delayed emptying. Decreased pyloric distensibility occurs with nausea, vomiting, and delayed gastric emptying. The EndoFLIP is a useful tool in the evaluation of pyloric function in symptomatic patients. PMID- 26813268 TI - [Screening, dignosis and follow-up in lung cancer in early stage]. PMID- 26813267 TI - Autosomal gsdf acts as a male sex initiator in the fish medaka. AB - Sex is pivotal for reproduction, healthcare and evolution. In the fish medaka, the Y-chromosomal dmy (also dmrt1bY) serves the sex determiner, which activates dmrt1 for male sex maintenance. However, how dmy makes the male decision via initiating testicular differentiation has remained unknown. Here we report that autosomal gsdf serves a male sex initiator. Gene addition and deletion revealed that gsdf was necessary and sufficient for maleness via initiating testicular differentiation. We show that gsdf transcription is activated directly by dmy. These results establish the autosomal gsdf as the first male sex initiator. We propose that dmy determines maleness through activating gsdf and dmrt1 without its own participation in developmental processes of sex initiation and maintenance. gsdf may easily become a sex determiner or other autosomal genes can be recruited as new sex determiners to initiate gsdf expression. Our findings offer new insights into molecular mechanisms underlying sex development and evolution of sex-controlling genes in vertebrates. PMID- 26813269 TI - [Spectrum of COL1A1/2 mutations and gene diagnosis in Chinese patients with osteogenesis imperfecta]. AB - OBJECTIVE: To identify mutations of the type I collagen genes (COL1A1 and COL1A2) in the affected with osteogenesis imperfecta (OI), to establish the spectrum of COL1A1/2 mutations in Chinese OI patients, and to provide prenatal gene diagnosis to the fetuses at high risk. METHODS: Genomic DNA was extracted from peripheral blood by the standard SDS-proteinase K-phenol/chloroform method. All the coding regions and exon/intron boundaries of COL1A1/2 were screened in 200 OI cases by conventional Sanger sequencing and targeted next-generation sequencing (NGS) on Ion Torrent-personalized genome sequencing operation (Ion PGMTM). For familial cases, candidate mutations were validated in all available family members using high resolution melting analysis (HRM). In sporadic cases, only parents were examined to determine the origin of the identified mutation.Prenatal gene diagnosis was carried out by PCR direct sequencing and linkage analysis using microsatellite markers. RESULTS: In total, the authors identified 125 differently pathogenic mutations, including 74 in COL1A1 and 51 in COL1A2, in 158 probands, with a mutation detection rate of 79% (158/200). Among the 125 identified mutations, there were 63 novel mutations (33 in COL1A1 and 30 in COL1A2) and 13 recurrent mutations found in 46 probands (seven mutations recurring for two times, and the other six mutations recurring for more than 4 times). They performed prenatal genetic testing in 74 fetuses and found that 40 ones carried COL1A1/2 mutations identified in the corresponding probands. CONCLUSIONS: The authors have developed a combined approach for genetic testing of OI, extended the COL1A1/2 mutation spectrum in Chinese OI patients, and confirmed gene diagnosis in a relatively large cohort of OI probands and fetuses. PMID- 26813270 TI - [Liver safety of biosimilar of recombinant tumor necrosis factor-alpha receptor antibody fusion protein in Spondyloarthritis patients under different status of HBV infection: a prospective observational study]. AB - OBJECTIVE: To investigate the influence of recombinant human tumor necrosis factor alpha receptor-antibody fusion protein (rhTNFR: Fc) to the Hepatitis B virus (HBV) infection status and liver function of Spondyloarthritis (SpA) patients under different HBV infection status. METHODS: Active SpA patients with normal liver function were enrolled in Sun Yat-sen Memorial hospital from February 2012 to August 2014. All were treated with rhTNFR: Fc based therapy (monotherapy or combined therapy) for at least 12 weeks. SpA disease activity, HBV infection status and liver function were evaluated at each interview (baseline, 4(th) and 12(th) week, as primary endpoint). Part of the patients were evaluated at 24(th) week with or without extended rhTNFR: Fc treatment(as secondary endpoint) based on their choice. RESULTS: Eighty-one patients who completed 12-week follow-up visit were divided into chronic HBV carrier group (n=21), past HBV exposure group (n=25) and free of HBV infection group (n=35). Alanine transaminase (ALT) elevated (no more than 3-fold of normal) in 3 patients from 3 groups respectively at 4th week. During 24-week follow-up, none in past HBV exposure group or in free of HBV infection group developed HBV reactivation or HBV infection; and 4 patients in chronic HBV carrier group developed HBV reactivation without more than 2-fold of normalelevation of ALT. Among 7 patients with negative baseline HBV-DNA and without antiviral prophylaxis, 2 patients developed HBV reactivation at 10(th) 24(th) week of rhTNFR: Fc therapy respectively and 1 patient developed reactivation at 16(th) week (12-week rhTNFR: Fc+ thalidomide therapy and following 4-week thalidomide monotherapy), whose HBV DNA load returned to normal spontaneously or after antiviral therapy. Four chronic HBV carriers with low-load of baseline HBV-DNA did not develop reactivation. One of 9 chronic HBV carriers with high-load of baseline HBV-DNA developed reactivation due to resistance of antiviral prophylaxis. CONCLUSIONS: Short-term rhTNFR: Fc based therapy may induce mild and transient HBV reactivation, usually without hepatitis. PMID- 26813271 TI - [Association between site of onset and ventilation dysfunction in patients with amyotrophic lateral sclerosis]. AB - OBJECTIVE: To study the association between site of onset and ventilation dysfunction in Chinese patients with amyotrophic lateral sclerosis. METHODS: The clinical data of 344 patients with sporadic amyotrophic lateral sclerosis (SALS) in Department of Neurology of Peking University Third Hospital from January 2009 to September 2013 were retrospectively reviewed. The differences of Forced Vital Capacity (FVC) between groups with distinct site of onset were analyzed. RESULTS: There were 55, 200 and 89 patients in the group with bulbar, upper limb and lower limb onset, respectively. The values of FVC were 84% +/- 14%, 83% +/- 17% and 88% +/- 16%, and the cases of FVC < 80% were 24 (43.64%), 81 (40.50%) and 25 (28.09%) in each group. The mean value of FVC was significantly lower and the frequency of FVC< 80% statistically higher in the group with upper limb onset in comparison with the group with lower limb onset. The mean value of FVC was lower and the frequency of FVC< 80% higher in the group with bulbar onset than in the group with lower limb onset. However, the differences were not significant between the two groups. CONCLUSIONS: Compared with SALS with upper limb onset, ventilation function disorder may occur less and later in patients with lower limb onset, who may also require noninvasive positive pressure ventilation (NIPPV) less and later. PMID- 26813272 TI - [Treatment of moyamoya disease by superficial temporal artery-middle cerebral artery anastomosis]. AB - OBJECTIVE: To explore the clinical efficacy and experiences of superficial temporal artery-middle cerebral artery anastomosis (STA-MCA) for the treatment of adult Moyamoya disease. METHOD: Preoperative and postoperative clinical data of 60 patients with moyamoya disease from affiliated hospital of jining medical college were analyzed retrospectively, including 46 cases of ischemic lesion and 14 cases of hemorrhage lesion. All patients were diagnosed with moyamoya disease by DSA and received STA-MCA anastomosis. RESULTS: The clinical symptoms of 52 patients disappeared after surgery; the clinical symptoms were improved in 6 patients; 1 patient complicated with cerebral infarction; 1 patients reoccurred cerebral hemorrhage broken into ventricles 1 year after anastomosis. CONCLUSION: STA-MCA anastomosis can improve the symptoms of ischemic moyamoya disease effectively and reduce the recurrence of cerebral hemorrhage. STA-MCA anastomosis is a rational and effective approach for the treatment of adult Moyamoya disease. PMID- 26813273 TI - [Image anatomic characteristics and clinical diagnosis and treatment of cerebral venous sinus stenosis]. AB - OBJECTIVE: To explore the imaging anatomic features of symptomatic cerebral venous sinus stenosis, and evaluate the efficacy and feasibility of different treatment methods. METHODS: From August 2001 to September 2004, 173 patients (transverse sinus stenosis 150, middle of the superior sagittal sinus stenosis 18, proximal part of sigmoid sinus stenosis 3, straight sinus stenosis 2; combined with sinus diverticulum 14, combined with Labbe's vein stenosis 3) were confirmed venous sinus stenosis by digital subtraction angiography (DSA). Among these patients, 121 were treated by stent implantation and the other 52 with mild symptoms by anticoagulation and/or thrombolysis treatment. RESULT: The treatment procedures were succeeded in all patients. 2 patients developed temporal and occipital hemorrhage during the procedure of artery thrombolysis, and 1 patient developed epidural hematoma in the transverse sinus area.All the 3 patients had a satisfactory prognosis through symptomatic treatment.There was no recurrence for all the patients during the follow-up period ranging from 1 to 9 years.9 patients who had recurring dizziness were confirmed no stent stenosis or thrombosis by DSA. The sites of stenosis in 168 patients (97%) were in the connect area of sigmoid and transverse sinuses or in the middle segment of superior sagittal sinus, where arachnoid granulations were focused on according to the anatomic characteristics. CONCLUSIONS: There is significant correlation between the cerebral venous sinuses stenosis and the abnormal growth of arachnoid granulations in the sinuses; the neurologic deficits caused by venous sinus stenosis can be relieved and eliminated by anticoagulation, thrombolysis, or stent implantation. Favorable medium-long term outcome is showed in the study population. PMID- 26813274 TI - [Characteristics and outcome of acute ischemic stroke patients with atrial fibrillation]. AB - OBJECTIVE: To evaluate clinical characteristics and outcome of acute ischemic stroke patients with atrial fibrillation. METHODS: Consecutive acute ischemic stroke patients who were hospitalized in the neurology department of General Hospital of Jinan Military Region were prospectively recruited from August 2010 to November 2013.The baseline datum including age, sex, National Institute of Health Stroke Scale (NIHSS), type of Oxfordshire Community Stroke Project (OCSP: total anterior circulation infarct, partial anterior circulation infarction, posterior circulation infarction and lacunar infarction), serum creatinine, serum albumin levels etc.were recorded.Atrial fibrillation (AF) was defined as a history of persistent atrial fibrillation or paroxysmal atrial fibrillation, supported by past electrocardiogram or diagnosed by the attending physicians based on physical examination, electrocardiogram and/or 24-hour electrocardiogram monitoring during hospitalization. Outcome was assessed by modified Rankin Scale (mRS) which was obtained 180 days after stroke by telephone interview (mRS <= 2 reflected good prognosis, and mRS>2 reflected unfavorable prognosis), and death defined as all-cause mortality. Multivariate regression model was used to analyze predictors of mortality and disability. RESULTS: Of the 965 patients included in this study, 113 (11.71%) had AF; valvular AF was observed in 11 patients (9.7%) among them.Only 4 patients with valvular AF and none of the patients with non valvular AF took warfarin before the stroke event. 14.2% (16/113) acute ischemic stroke patients with AF took aspirin. Compared to patients without AF, patients with AF had a higher NIHSS score on admission (median 11 vs 5, P=0.000); were more often with diabetes (26.55% vs 9.74%, P=0.028), congestive heart failure (12.37% vs 11.03%, P=0.000), prior stroke (31.86% vs 21.83%, P=0.023), total anterior circulation infarct subtype (51.33% vs 19.37%, P=0.000); they were less often smokers (20.35% vs 37.32%, P=0.000), alcohol consumers (13.27% vs 27.58%, P=0.001), partial anterior circulation infarction subtype (24.78% vs 36.74%, P=0.012), lacunar infarct subtype (0 vs 17.61%, P=0.000); they had less often experienced myocardial infarction (11.50% vs 11.74%, P=0.041). AF was a significant independent prognostic factor for long-term poor outcomes (OR=2.227, 95%CI: 1.262-3.933, P=0.006). CONCLUSIONS: Oral anticoagulants are underused in AF patients.Brain infarction patients with AF is more severe than patients without AF; have higher frequency of total anterior circulation infarct subtype, prior stroke and lower frequency of lacunar infarct subtype. AF is a significant independent prognostic factor for long-term poor outcome in patients with acute brain infarction. PMID- 26813275 TI - [CT perfusion imaging evaluation on hemodynamic changes of acute spontaneous intracerebral hemorrhage surrounding tissues]. AB - OBJECTIVE: To discuss the hemodynamic changes in patients with acute supratentorial spontaneous intracerebral hemorrhage (within 72 hours) by using 320-slice of low-dose volume CT perfusion imaging. METHODS: Twenty-six patients of The First Affiliated Hospital of Wenzhou Medical University during December 2012 to December 2013 with acute supratentorial SICH diagnosed by plain CT scanning and clinic were enrolled. With hematoma maximum level for reference, the hematoma volume, edema area and perfusion defect area were measured, and the perfusion parameters values of the marginal area and outer area of the intracerebral hematoma and contralateral mirror area were measured, including cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time-to-peak (TTP), and rCBF, rCBV, rMTT and rTTP were calculated by ipsilateral/contralateral value. RESULTS: The CBF, CBV of the marginal area were lower than the contralateral mirror area (tCBF=-8.125, tCBV=-8.671, PCBF, CBV<0.01); the MTT of the marginal area was shorter than the contralateral mirror area (tMTT=-3.246, PMTT<0.05); the TTP of the marginal area was longer than the contralateral mirror area (tTTP=5.027, PTTP<0.01). The CBV of the outer area was lower than the contralateral mirror area (tCBV=-2.337, PCBV<0.05); the MTT of the outer area was shorter than the contralateral mirror area (tMTT=-2.421, PMTT<0.05); the TTP of the outer area was longer than the contralateral mirror area (tTTP=2.077, PTTP<0.05). There was a siginificant relationship between the volume of acute hematoma and rCBV, rMTT, rTTP of the marginal area (rrCBV=-0.412, PrCBV<0.05, rrMTT=-0.437, PrMTT<0.05, rrTTP=0.475, PrMTT<0.05). Perihematomal CBF perfusion defect area showed a positive linear relation with the volume of acute hematoma (r=0.440, P<0.05). There was a positive linear relationship between the maximum level edema area and the hematoma volume, perihematomal CBF perfusion defect area (r=0.400, r=0.81, P<0.05). CONCLUSIONS: 320-slice of low-dose and volume CT perfusion imaging can perfectly reflect the hemodynamic changes in brain tissuse after acute supratentorial SICH. Hypoperfusion was appeared in perihematomal area of acute supratentorial SICH. The perihematomal brain tissue may exists ischemic injury associated with the size of hematoma.The hematoma place holder effect, ischemic injury are the important cause of acute brain edema formation. PMID- 26813276 TI - [Study on the hemodynamic changes in solid thyroid nodules by ultrasound contrast quantitative analysis]. AB - OBJECTIVE: To compare the difference between the different perfusional regions in solid thyroid nodules. METHODS: From October 2013 to May 2015, CEUS was performed in 59 patients who hospitalizated in Zhoushan Hospital with solid thyroid nodules before operation. The time-intensity curve (TIC) of normal thyroid tissue, tumor edge and tumor center was drawn to collect perfusion index like the peak intensity (PI), time to peak (TP), area under the curve (AUC), mean transit time (MTT). After surgery, immunohistochemical staining was performed to evaluate the MVD in surgical specimens.Quantitative parameters and MVD were assessed by the Spearman correlation analysis. RESULTS: There were 31 thyroid papillary carcinomas and 28 nodular goiters. In malignant tumor group, the PI of normal thyroid tissue, tumor edge and tumor center were 28% +/- 6%, 21% +/- 7% and 14% +/- 5%, respectively, while the AUC and MVD of the same regions were (1 865 +/- 1 079)%S, (1 376 +/- 595)%S, (805 +/- 412)%S and(33 +/- 6), (27 +/- 6)/HP, (17 +/- 6)/HP, respectively. The differences were statistically significant. However, in benign tumor group, there was no obvious statistic difference in the quantitative parameters and MVD between the three regions. The PI values of thyroid carcinomas and nodular goiters all were positively correlated with MVD (r=0.819, r=0.838, P<0.05). CONCLUSIONS: The variance of perfusion parameters were valuable diagnostic basis in differential diagnosis between benign and malignant thyroid nodules. They were associated with MVD, which might reflect the microvessel distributional characteristics of neoplasm and might be one of bases used to evaluate neoplasm angiogenesis. PMID- 26813277 TI - [Occurrence and outcome of left ventricular-arterial coupling in sepsis-induced cardiomyopathy]. AB - OBJECTIVE: To explore the occurrence and development of sepsis-induced cardiomyopathy (SIC) and its correlation with left ventricular arterial coupling. METHODS: A total of 46 SIC patients were recruited and divided into non-survival and survival groups. And hemodynamics parameters, lactate, cardiac elastance (Ees), arterial elastance (Ea) and ventricular-arterial coupling (Ea/Ees), stroke work (SW), total mechanical work (PVA) and cardiac work efficiency (SW/PVA) were recorded before and after an onset of SIC. RESULTS: The occurrence and development of SIC had close correlations with left ventricular arterial coupling.Heart and arterial elastance affected the occurrence and outcome of SIC. The former was a underlying cause while the latter a precipitating factor; the primary treatment goal of SIC was improving ventricular-arterial coupling. And the short-term objective was reducing arterial elastance and long-term strategy improving cardiac elastance; Ea declined initially when SIC recovered. And it was consistent with ventricular-arterial coupling improvement. Ees recovery was delayed; before and after SIC, low peripheral vascular resistance within 36 h could reduce arterial elastance Ea; ventricular artery coupling affected cardiac external work, work efficiency and stroke volume and was associated with tissue perfusion. CONCLUSION: The occurrence and outcome of SIC are simultaneously influenced by Ees and Ea and are closely correlated with Ea/Ees. Treatment goal of SIC is improving ventricular-arterial coupling.Ea should be reduced within 36 h and Ees should be boosted after 48 h. PMID- 26813278 TI - [Comparison of clinical results between middle-aged patients and young patients after anterior cruciate ligament reconstruction]. AB - OBJECTIVE: To compare the outcomes of anterior cruciate ligament (ACL) reconstruction in patients aged over 40 years and under 25 years at least 24 months follow-up after operation. METHODS: Fifty-seven patients who underwent ACL reconstruction for ACL rupture in Institute of Sports Medicine, Peking University Third Hospital, from October 2010 to December 2012 were selected for this retrospective study.The patients aged over 40 years consisted of 13 men and 15 women with an average age of 46.5 years (range, 41 to 63 years). The patients younger than 25 years consisted of 19 men and 10 women with an average age of 21.0 years (range, 18 to 24 years). The average follow-up time was 26.0 months (range, 24 to 45 months). Clinical functional evaluation for all patients was performed according to Lysholm, Tegner and IKDC scores both before and after surgery.In addition, a pre- and post-operative arthrometric evaluation was also performed with KT-2000. RESULTS: The average postoperative Lysholm, Tegner and IKDC scores in patients aged over 40 years and under 25 years were 89 (74 to 100), 5 (3 to 6), 90 (70 to 100) and 94 (79 to 100), 5 (4 to 7), 93 (74 to 100) respectively.The average postoperative KT-2000 arthrometer anterior laxity in 30 degrees and 90 degrees in both groups was 2 mm (0 to 4 mm), 1 mm (-1 to 4 mm) and 2 mm (0 to 4 mm), 1 mm (0 to 4 mm) respectively.The postoperative functional scores and side-to-side difference improved more significantly than preoperative values, with no significant difference in both groups. CONCLUSION: ACL reconstruction provides the comparable clinical outcomes between middle-aged patients and young patients. PMID- 26813279 TI - [Expression and clinical significance of ING4 and HIF-1 alpha in brain astrocytoma]. AB - OBJECTIVE: To study the mRNA expression level of growth inhibition factor 4 (ING4) and hypoxia inducing factor 1 alpha (HIF-1 alpha), and their relationship with tumor malignant degree or the pathology classification in human brain astrocytoma. METHODS: The mRNA expression levels of ING4 and HIF-1 alpha were detected by RT-PCR method in 45 cases of grade I-IV human brain astrocytoma and 11 cases of control brain tissues from January 2009 to June 2010 in the Second Affiliated Hospital of Zhengzhou University, and their correlation was also analyzed. RESULTS: In the non-tumor brain tissue, the expression level of ING4 mRNA was 1.19 +/- 0.22, while they were 0.91 +/- 0.19, 0.74 +/- 0.28, 0.54 +/- 0.33 and 0.22 +/- 0.19 in I-IV grade astrocytoma, respectively. Compared with the non-tumor control, the mRNA expression level of ING4 gene decreased significantly in the astrocytoma (P<0.05). And the expression of ING4 gradually reduced with the increase of the pathological classification of the astrocytoma.In the non tumor brain tissue, the expression level of HIF-1 alpha mRNA was 0.26 +/- 0.16, and they were 0.34 +/- 0.19, 0.50 +/- 0.23, 0.96 +/- 0.15 and 1.04 +/- 0.15 in I IV grade astrocytoma, respectively.For HIF-1 alpha gene, the mRNA expression level increased significantly in the astrocytoma. Meanwhile, the expression gradually increased with the increase of the pathological classification of the astrocytoma (P<0.05). The mRNA expression showed a negative correlation between ING4 and HIF-1 alpha with the increase of the tumor malignant degree. CONCLUSION: The ING4 and HIF-1 alpha genes play a role in the tumorigenesis and development of human brain astrocytoma, and closely associate with the malignant degree of astrocytoma. PMID- 26813280 TI - [Effect analysis of multi-electrode synchronous radiofrequency ablation and conventional single electrode overlapping ablation]. AB - OBJECTIVE: To explore the different effects in ex vivo bovine liver between multiple cool-tip internally cooled electrodes synchronous radiofrequency ablation via switching controller and conventional single electrode overlapping radiofrequency ablation. METHOD: The above two methods were used to ablate in ex vivo bovine liver respectively. Electrode exposed end was 3 cm or 4 cm in length. The morphological characteristics of lesions created by two methods were observed, the sizes of the ablated lesions were measured and compared. RESULT: The formation of lesions ablated by both two methods was ellipsoidal. The longitudinal diameter, transverse diameter, front-end diameter and volume of the lesions ablated 16 mins by multi-electrode synchronous radiofrequency ablation via switching controller were (7.12 +/- 0.52) cm, (5.71 +/- 0.47) cm, (1.77 +/- 0.29) cm, (102 +/- 20) cm3, respectively. All of them are larger than the lesions ablated 36 mins by conventional single electrode overlapping radiofrequency ablation (P<0.01). At the same 16 mins, multi-electrode synchronous radiofrequency ablation via switching controller created longer longitudinal diameter and large volume (P<0.01) with longer exposed end electrodes (4 cm vs 3 cm). But the transverse diameter, the front-end diameter had no statistical difference (P>0.05). CONCLUSION: Compared with the conventional single electrode overlapping radiofrequency ablation, multi-electrode synchronous radiofrequency ablation via switching controller create larger lesion in the shorter time. It may provide a new attempt for the clinical treatment of large hepatocellular carcinoma. PMID- 26813281 TI - [Effects of emodin-8-O-beta-D-glucoside on cell apoptosis and expression of Bcl 2/Bax in cervical cancer SKOV3 cells]. AB - OBJECTIVE: To explore the effect of emodin-8-O-beta-D-glucoside (EG) on cell apoptosis and expression levels of Bcl-2 family proteins in human ovarian cancer SKOV3 cells. METHODS: SKOV3 cells were cultured and divided into two groups (control group and experimental group). Cell viabilities were determined by the methyl thiazolyl tetrazolium (MTT) method; apoptosis and cell cycle were analyzed by flow cytometry; the changes of protein expression of cleaved caspase-3, cleaved caspase-9, Bcl-2 and Bax were detected by Western blot. RESULTS: From the data of MTT, the cell proliferation of human ovarian cancer SKOV3 cells was inhibited by EG (20, 40, 80 mg/L) in a dose- and time-dependent manner. Flow cytometry assays showed that EG significantly induced apoptosis in SKOV3 cells. 48 h after treated with EG (20, 40, 80 mg/L), the apoptosis rate of the experimental group were increased gradually, and they were 23.8%, 35.5%, 59.6%, respectively, which were higher than these of the control group significantly. The data of Western blot showed that EG down-regulated Bcl-2 and up-regulated cleaved caspase-3, cleaved caspase-9, Bax in a dose-dependent manner. CONCLUSIONS: EG can inhibit the proliferation of SKOV3 cells and promote apoptosis, and the anticancer effect of EG may be associated with the down regulation of Bcl-2 expression and up regulation of Bax expression, as well as the increase of relative activity of caspase 3 and caspase 9. EG may be a promising antitumor agent for cancer treatment. PMID- 26813282 TI - [Effects of mild hypothemia on hemodynamics of systemic and renal of dog with septic shock]. AB - OBJECTIVES: To explore the effects of mild hypothemia on hemodynamics of systemic and renal of dog with septic shock. METHODS: 40 healthy dogs were randomly and evenly divided into the normal temperature non-infected group (NTNS), normal temperature infected group (NTS), hypothermia non-infected group (MHNS) and hypothermia infected group (MHS). NTS and MHS were pumped through the femoral vein of Escherichia coli (E.coli 1 * 109 cfu/ml) by 0.5 ml.kg-1.h-1, producting septic shock model with high-power cycle. Combining with blood pump devices and low temperature thermostat bath, the MHNS and MHS implemented extracorporeal blood cooling method to maintain the blood in temperature (33 +/- 1) degrees C. 0, 24, 48, 72 h point, tested specimens from femoral vein for renal function. In the 0-72 h. Pulse indicates the continuous cardiac output monitor (PiCCO) monitored systemic hemodynamics on each time point. In the 0-72 h, color Doppler ultrasound (CDFI) measured renal hemodynamic on each time point. RESULTS: There was an increase of SBP (P<0.05), SVR [(2 415 +/- 651) dyn.s.cm-5 vs (1 613 +/- 223) dyn.s.cm-5, P=0.01] and RI (P=0.04) in the MHS group comparing with the NTS group from 24 to 72 h. CO [(3.58 +/- 0.44) L/min vs (4.18 +/- 0.60) L/min, P=0.04], HR and PSV was decreased in the MHS group. BUN [(8.6 +/- 1.6) mmol/L vs (21.2 +/- 4.8) mmol/L, P<0.01] and Scr [(167.6 +/- 31.2) umol/L vs (383.8 +/- 35.2) umol/L, P<0.01] was decreased in MHS group comparing with the NTS group. There was a positively correlation between CO and PSV in the canine model of septic shock (P<0.01); and CO was negatively correlated with RI (P<0.01). CONCLUSIONS: In this canine model of septic shock, hypothermia can stable systemic and renal hemodynamics, and improve kidney function. PMID- 26813284 TI - Corrigendum: Revealing the nanoparticles aspect ratio in the glass-metal nanocomposites irradiated with femtosecond laser. PMID- 26813283 TI - Syndactyly in a novel Fras1(rdf) mutant results from interruption of signals for interdigital apoptosis. AB - BACKGROUND: Fras1 encodes an extracellular matrix protein that is critical for the establishment of the epidermal basement membrane during gestation. In humans, mutations in FRAS1 cause Fraser Syndrome (FS), a pleiotropic condition with many clinical presentations such as limb, eye, kidney, and craniofacial deformations. Many of these defects are mimicked by loss of Fras1 in mice, and are preceded by the formation of epidermal blisters in utero. RESULTS: In this study, we identified a novel ENU-derived rounded foot (rdf) mouse mutant with highly penetrant hindlimb soft-tissue syndactyly, among other structural defects. Mapping and sequencing revealed that rdf is a novel loss-of-function nonsense allele of Fras1 (Fras1(rdf)). Focusing on the limb, we found that the Fras1(rdf) syndactyly phenotype originates from loss of interdigital cell death (ICD). Despite normal expression of bone morphogenetic protein (BMP) ligands and their receptors, the BMP downstream target gene Msx2, which is also necessary and sufficient to promote ICD, was down-regulated in the interdigital regions of Fras1(rdf) hindlimb buds. CONCLUSIONS: The close correlation between limb bud epidermal blistering, decreased Msx2 expression, and reduced ICD in the Fras1(rdf) hindlimb buds suggests that epithelium detachment from the mesenchyme may create a physical gap that interrupts the transmission of BMP, among other signals, resulting in soft tissue syndactyly. PMID- 26813285 TI - Spinocerebellar ataxia type 21 exists in the Chinese Han population. AB - Recently, mutations in transmembrane protein 240 (TMEM240) were identified as the cause of spinocerebellar ataxia type 21 (SCA21) in several French families. Clinically, SCA21 is characterized as an early-onset, slowly progressive cerebellar syndrome typically associated with cognitive impairment. To date, molecular screening of SCA21 has not been reported among patients of other ethnic origins or in other areas. Here we used Sanger sequencing to detect mutations in exons of TMEM240 in 340 unrelated probands with spinocerebellar ataxia for whom commonly known causative mutations have been excluded (96 probands of autosomal dominant spinocerebellar ataxia families and 244 patients with sporadic spinocerebellar ataxia). As a result, a de novo missense mutation (c.509C > T/p.P170L) was identified in one sporadic SCA patient. The condition manifested as early-onset (30 years old), slowly progressive cerebellar ataxia accompanied by mild early evidenced mental retardation, mild frontal behavior disorders and intentional hand tremors. Although rare, a SCA21 case was identified and described in mainland China, thus broadening the ethnic distribution of SCA21 beyond French families. PMID- 26813286 TI - Defining competencies for the practice of telepsychiatry through an assessment of resident learning needs. AB - BACKGROUND: A foundational assessment of learning needs is missing from previous reports of telepsychiatry curricula. We used an in-depth needs assessment to identify specific skills required for the practice of effective telepsychiatry, and provide an evidence base to guide the development of telepsychiatry curricula in postgraduate psychiatry training. Many of these skills set telepsychiatry apart from practice in traditional face-to-face clinical settings, or result from adaptations to clinical practice to meet the needs of a telepsychiatry interface in patient care. METHODS: We used a qualitative, modified grounded theory approach to gain insight into areas of importance for telepsychiatry training in postgraduate psychiatry residency. 16 interviews of faculty and residents (9 and 7 interviews, respectively), allowed participants to reflect on their experiences in telepsychiatry. Data were then thematically analyzed. RESULTS: Interview respondents identified important aspects of the context for telepsychiatry training; the skills required to competently practice telepsychiatry; and the desired teaching and learning methods for acquiring these skills. Specific domains of competency were identified: technical skills; assessment skills; relational skills and communication; collaborative and interprofessional skills; administrative skills; medico-legal skills; community psychiatry and community specific knowledge; cultural psychiatry skills, including knowledge of Indigenous cultures; and, knowledge of health systems. The skills identified in this study map well to competency- based medical education frameworks. CONCLUSIONS: Telepsychiatry is increasingly being adopted as a solution to health systems problems such as regional disparities in access to care, and it requires explicit competency development. Ensuring adequate and quality exposure to telepsychiatry during residency training could positively impact our health systems and health equity. PMID- 26813287 TI - Tandem Intramolecular Diels-Alder/1,3-Dipolar Cycloaddition Cascade of 1,3,4 Oxadiazoles: Initial Scope and Applications. AB - A summary of the development and initial studies on the scope of a powerful tandem intramolecular [4 + 2]/[3 + 2] cycloaddition cascade of 1,3,4-oxadiazoles is detailed and provides the foundation for its subsequent use in organic synthesis. Implemented with substrates in which both the initiating dienophile and subsequent dipolarophile are tethered to the 1,3,4-oxadiazoles, the studies expanded the scope of oxadiazoles that participate in the reaction cascade, permitted the use of differentiated dienophiles and dipolarophiles, extended their use to unsymmetrical dienophiles and dipolarophiles, provided exclusive control of the cycloaddition regioselectivities, and imposed exquisite control on the cycloaddition stereochemistry. As key reactivity and stereochemical features of the reactions were being defined, the cascade cycloaddition reaction was implemented in the total synthesis of a series of alkaloids including (-) vindoline, (-)-vindorosine, the closely related natural products (+)-4 desacetoxyvindoline and (+)-4-desacetoxyvindorosine, natural minovine, (+)-N methylaspidospermidine, (+)-spegazzinine, (-)-aspidospermine, and a number of key analogues. Most recently, it was used in the divergent total syntheses of (+) fendleridine, (-)-kopsinine, (-)-kopsifoline D, and (-)-deoxoapodine, in which four different strategic bonds in four different classes of the hexacyclic alkaloids were formed from a common cascade cycloaddition intermediate. A large number of vindoline analogues were prepared by variations on the cascade cycloaddition reaction for single step incorporation into analogues of vinblastine. These structural changes to vindoline permitted both systematic alterations to the peripheral substituents as well as deep-seated changes to the core structure and embedded functionality of vinblastine not previously accessible. Although explored initially for accessing vindoline and vinblastine, the use of the cycloaddition cascade in the total synthesis of an impressive range of additional natural products illustrate the power of the methodology. Alternative tethering strategies for the cascade cycloaddition reaction, combined intramolecular and intermolecular variants of either the initiating Diels-Alder reaction or the subsequent carbonyl ylide 1,3-dipolar cycloaddition, an expanded examination of the tethered dipolarophile scope, and applications to additional natural product classes represent attractive areas for future work. PMID- 26813289 TI - Next-generation resorbable polymer scaffolds with surface-precipitated calcium phosphate coatings. AB - Next-generation synthetic bone graft therapies will most likely be composed of resorbable polymers in combination with bioactive components. In this article, we continue our exploration of E1001(1k), a tyrosine-derived polycarbonate, as an orthopedic implant material. Specifically, we use E1001(1k), which is degradable, nontoxic, and osteoconductive, to fabricate porous bone regeneration scaffolds that were enhanced by two different types of calcium phosphate (CP) coatings: in one case, pure dicalcium phosphate dihydrate was precipitated on the scaffold surface and throughout its porous structure (E1001(1k) + CP). In the other case, bone matrix minerals (BMM) such as zinc, manganese and fluoride were co precipitated within the dicalcium phosphate dihydrate coating (E1001(1k) + BMM). These scaffold compositions were compared against each other and against ChronOS (Synthes USA, West Chester, PA, USA), a clinically used bone graft substitute (BGS), which served as the positive control in our experimental design. This BGS is composed of poly(lactide co-epsilon-caprolactone) and beta-tricalcium phosphate. We used the established rabbit calvaria critical-sized defect model to determine bone regeneration within the defect for each of the three scaffold compositions. New bone formation was determined after 2, 4, 6, 8 and 12 weeks by micro-computerized tomography (MUCT) and histology. The experimental tyrosine derived polycarbonate, enhanced with dicalcium phosphate dihydrate, E1001(1k) + CP, supported significant bone formation within the defects and was superior to the same scaffold containing a mix of BMM, E1001(1k) + BMM. The comparison with the commercially available BGS was complicated by the large variability in bone formation observed for the laboratory preparations of E1001(1k) scaffolds. At all time points, there was a trend for E1001(1k) + CP to be superior to the commercial BGS. However, only at the 6-week time point did this trend reach statistical significance. Detailed analysis of the MUCT data suggested an increase in bone formation from 2 through 12 weeks in implant sites treated with E1001(1k) + CP. At 2 and 4 weeks post-implantation, bone formation occurred at the interface where the E1001(1k) + CP scaffold was in contact with the bone borders of the implant site. Thereafter, during weeks 6, 8 and 12 bone formation progressed throughout the E1001(1k) + CP test implants. This trend was not observed with E1001(1k) + BMM scaffolds or the clinically used BGS. Our results suggest that E1001(1k) + CP should be tested further for osteoregenerative applications. PMID- 26813288 TI - Epigenomic analysis detects aberrant super-enhancer DNA methylation in human cancer. AB - BACKGROUND: One of the hallmarks of cancer is the disruption of gene expression patterns. Many molecular lesions contribute to this phenotype, and the importance of aberrant DNA methylation profiles is increasingly recognized. Much of the research effort in this area has examined proximal promoter regions and epigenetic alterations at other loci are not well characterized. RESULTS: Using whole genome bisulfite sequencing to examine uncharted regions of the epigenome, we identify a type of far-reaching DNA methylation alteration in cancer cells of the distal regulatory sequences described as super-enhancers. Human tumors undergo a shift in super-enhancer DNA methylation profiles that is associated with the transcriptional silencing or the overactivation of the corresponding target genes. Intriguingly, we observe locally active fractions of super enhancers detectable through hypomethylated regions that suggest spatial variability within the large enhancer clusters. Functionally, the DNA methylomes obtained suggest that transcription factors contribute to this local activity of super-enhancers and that trans-acting factors modulate DNA methylation profiles with impact on transforming processes during carcinogenesis. CONCLUSIONS: We develop an extensive catalogue of human DNA methylomes at base resolution to better understand the regulatory functions of DNA methylation beyond those of proximal promoter gene regions. CpG methylation status in normal cells points to locally active regulatory sites at super-enhancers, which are targeted by specific aberrant DNA methylation events in cancer, with putative effects on the expression of downstream genes. PMID- 26813290 TI - Periodontal Health Condition and Associated Factors among University Students, Yemen. AB - INTRODUCTION: Studies on oral health status among Yemeni population are scarce. AIM: This study aimed to evaluate the periodontal health among advantaged section of Yemeni society, university students, in health and non-health fields. MATERIALS AND METHODS: Periodontal health status of a sample of 360 students from dental, medical and literature faculties (120 each with equal gender distribution) at Sana'a University was evaluated by two calibrated examiners using CPI index. Data regarding tooth-brushing practices and smoking and khat chewing habits were obtained using a structured interview questionnaire. RESULTS: Only 45 students (12.5%) had healthy periodontium, while 113 (31.4%), 186 (51.7%) and 16 (4.4%) had bleeding, calculus and shallow pocket, respectively, with no significant differences between faculties. Females revealed significantly better periodontal health compared to males, though their bleeding score was higher. Dental and medical students and female students in general were significantly more interested in tooth-brushing and significantly less interested in practicing the deleterious habits such as smoking and khat chewing. CONCLUSION: The overall periodontal health of Sana'a University students is still unsatisfactory even among students in health field. Females and students in health field revealed better periodontal health and oral health practices (tooth-brushing) in comparison to male students and those in non-health field. The negative effects of the highly prevalent smoking and khat chewing habits deserve further reliable researches and proper educational programs at the national level. PMID- 26813291 TI - Bioorthogonal chemistry for selective recognition, separation and killing bacteria over mammalian cells. AB - By taking advantage of metabolic engineering and bioorthogonal click chemistry, we report a new strategy for selective recognition, separation and killing bacteria over mammalian cells. PMID- 26813292 TI - Interaction of a live attenuated Salmonella Gallinarum vaccine candidate with chicken bone marrow-derived dendritic cells. AB - Salmonella enterica serovar Gallinarum (SG) is a Gram-negative intracellular host adapted pathogen that causes fowl typhoid. Attenuated strains of SG are proven and widely used vaccine candidates because of advantages like induction of strong humoral and cell-mediated immune responses. In the present study, we investigated the interaction of chicken bone marrow-derived dendritic cells (chBM-DCs) with an attenuated SG (JOL1355) strain that secretes a heat-labile enterotoxin B subunit protein previously shown to successfully vaccinate chickens. ChBM-DCs were isolated and cultured in the presence of recombinant chicken GM-CSF and IL-4 cytokines. The chBM-DCs were infected with JOL1355 at an multiplicity of infection of 10. JOL1355 was able to invade dendritic cells (DCs); however, the survival of JOL1355 in DCs decreased over time. At 24 h post infection, IL-6, IL 10 and IFN-gamma transcript levels were significantly increased in JOL1355 infected DCs compared to non-stimulated DCs. Flow cytometry analysis showed an increased proportion of cells producing CD40, CD80, and MHC class II in the JOL1355-infected cultures compared to the non-stimulated control. In addition, JOL1355-stimulated chBM-DCs could induce significant expression of IL-2 in co culture with autologous CD4+ T cells. Based on these results, we conclude that chBM-DCs are capable of internalizing the live attenuated SG vaccine candidate and the infected chBM-DCs show signs of maturation as evidenced by the upregulated expression of costimulatory molecules and cytokines. PMID- 26813294 TI - Commentary on refractory ischemic priapism. PMID- 26813295 TI - Discrimination of bacteriophage infected cells using locked nucleic acid fluorescent in situ hybridization (LNA-FISH). AB - Bacteriophage-host interaction studies in biofilm structures are still challenging due to the technical limitations of traditional methods. The aim of this study was to provide a direct fluorescence in situ hybridization (FISH) method based on locked nucleic acid (LNA) probes, which targets the phage replication phase, allowing the study of population dynamics during infection. Bacteriophages specific for two biofilm-forming bacteria, Pseudomonas aeruginosa and Acinetobacter, were selected. Four LNA probes were designed and optimized for phage-specific detection and for bacterial counterstaining. To validate the method, LNA-FISH counts were compared with the traditional plaque forming unit (PFU) technique. To visualize the progression of phage infection within a biofilm, colony-biofilms were formed and infected with bacteriophages. A good correlation (r = 0.707) was observed between LNA-FISH and PFU techniques. In biofilm structures, LNA-FISH provided a good discrimination of the infected cells and also allowed the assessment of the spatial distribution of infected and non infected populations. PMID- 26813297 TI - Screening at hair salons: The feasibility of using community resources to screen for intimate partner violence. AB - BACKGROUND: Intimate partner violence (IPV) is a source of severe health consequences, and therefore, health care organizations have recommended routine IPV screening. Implementing health-related screenings outside of health care facilities is common public health practice, but to date, IPV screening in hair salons has not been reported. The objective of this study was to determine the prevalence of IPV among women at hair salons. We hypothesized that women would disclose IPV in this setting and that rates of abuse would reflect national averages. METHODS: We recruited a convenience sample of hair salons in Connecticut in 2014. Hair stylists were trained on how to recognize and refer IPV victims. Self-reported IPV of salon clients was measured by a tablet-based validated screening tool, the Patient Satisfaction and Safety Survey. RESULTS: Overall, reported past-year prevalence of physical abuse was 3.6%, past-year prevalence of sexual abuse was 2.7%, lifetime prevalence of emotional or physical abuse was 34.2%, and 5.3% of the sample reported that they had been hurt that day by their current or former partner. Past-year physical abuse was more common among women 30 years to 39 years old (9.1%), black (9%), and single women (7.5%). Past-year sexual abuse was more common among women 20 years to 29 years old (13.8%), other races (6.7%), and single women (5.4%). Lifetime abuse was more common among women 50 years to 59 years old (13.8%), black (36.1%), and divorced women (69.7%). Hurt-today abuse was more common among women younger than 20 years (12.5%), other races (13.3%), and women in common law relationships (25%). CONCLUSION: Women in our study reported IPV prevalence rates consistent with national data. Documentation of IPV prevalence in hair salons will provide much needed support for novel interventions such as CUT IT OUT, a national program designed to train hair stylists on how to recognize and refer IPV victims. PMID- 26813296 TI - Evidence of suppression of onchocerciasis transmission in the Venezuelan Amazonian focus. AB - BACKGROUND: The World Health Organization (WHO) has set goals for onchocerciasis elimination in Latin America by 2015. Most of the six previously endemic countries are attaining this goal by implementing twice a year (and in some foci, quarterly) mass ivermectin (Mectizan(r)) distribution. Elimination of transmission has been verified in Colombia, Ecuador and Mexico. Challenges remain in the Amazonian focus straddling Venezuela and Brazil, where the disease affects the hard-to-reach Yanomami indigenous population. We provide evidence of suppression of Onchocerca volvulus transmission by Simulium guianense s.l. in 16 previously hyperendemic Yanomami communities in southern Venezuela after 15 years of 6-monthly and 5 years of 3-monthly mass ivermectin treatment. METHODS: Baseline and monitoring and evaluation parasitological, ophthalmological, entomological and serological surveys were conducted in selected sentinel and extra-sentinel communities of the focus throughout the implementation of the programme. RESULTS: From 2010 to 2012-2015, clinico-parasitological surveys indicate a substantial decrease in skin microfilarial prevalence and intensity of infection; accompanied by no evidence (or very low prevalence and intensity) of ocular microfilariae in the examined population. Of a total of 51,341 S. guianense flies tested by PCR none had L3 infection (heads only). Prevalence of infective flies and seasonal transmission potentials in 2012-2013 were, respectively, under 1% and 20 L3/person/transmission season. Serology in children aged 1-10 years demonstrated that although 26 out of 396 (7%) individuals still had Ov-16 antibodies, only 4/218 (2%) seropositives were aged 1-5 years. CONCLUSIONS: We report evidence of recent transmission and morbidity suppression in some communities of the focus representing 75% of the Yanomami population and 70% of all known communities. We conclude that onchocerciasis transmission could be feasibly interrupted in the Venezuelan Amazonian focus. PMID- 26813298 TI - Botulinum toxin A-induced paralysis of the lateral abdominal wall after damage control laparotomy: A multi-institutional, prospective, randomized, placebo controlled pilot study. AB - BACKGROUND: Damage-control laparotomy (DCL) is a lifesaving operation used in critically ill patients; however, interval primary fascial closure remains a challenge. We hypothesized that flaccid paralysis of the lateral abdominal wall musculature induced by botulinum toxin A (BTX) would improve rates of primary fascial closure, decrease duration of hospital stay, and enhance pain control. METHODS: Consenting adults who had undergone a DCL at two institutions were prospectively randomized to receive ultrasound-guided injections of their external oblique, internal oblique, and transversus abdominus muscles with either BTX (150 mL, 2 U/mL) or placebo (150-mL 0.9% NaCl). Patients were excluded if they had a body mass index of greater than 50, remained unstable or coagulopathic, were home O2 dependent, or had an existing neuromuscular disorder. Outcomes were assessed in a double-blinded manner. Univariate and Kaplan-Meier estimates of cumulative probability of abdominal closure were performed. RESULTS: We randomized 46 patients (24 BTX, 22 placebo). There were no significant differences in demographics, comorbidities, and physiologic status. Injections were performed on average 1.8 +/- 2.8 days (range, 0-14 days) after DCL. The 10 day cumulative probability of primary fascial closure was similar between groups: 96% for BTX (95% confidence interval [CI], 72-99%) and 93% for placebo (95% CI, 61-99%) (HR, 1.0; 95% CI, 0.5-1.8). No difference between BTX and placebo groups was observed for hospital length of stay (37 days vs. 26 days, p = 0.30) or intensive care unit length of stay (17 days vs. 11 days, p = 0.27). There was no difference in median morphine equivalents following DCL. The overall complication rate was similar (63% vs. 68%, p = 0.69), with two deaths in the placebo group and none in the BTX group. No BTX or injection procedure complications were observed. CONCLUSION: The use of BTX after DCL was safe but did not seem to affect primary fascial closure, hospital length of stay, or pain modulation after DCL. Given higher-than-expected rates of primary fascial closure, Type II error may have occurred. LEVEL OF EVIDENCE: Therapeutic study, level III. PMID- 26813301 TI - Hitting rock bottom? Resource loss as a predictor of alcoholism treatment completion. AB - Background Efforts to better understand the phenomenon of the 'bottom', the beginning of the process of turning away from alcohol, are important for both theoretical and practical goals. The conservation of resources theory by Hobfoll may represent a suitable framework to base these attempts around. Aim The aim of the study was to examine the role of resource loss in completing alcoholism treatment on the basis of Hobfoll's conservation of resources theory. Methods The study included 86 patients undergoing inpatient alcoholism treatment. An assessment of resource loss and gain during the previous year, as well as of the decisional balance regarding the pros and cons of drinking alcohol, took place at the beginning of therapy. Results The results of hierarchical binary logistic regression confirmed that resource loss was the only significant predictor of therapy completion, after adjustment for decisional balance, demographics and basic clinical data. Additionally, gender moderated the relationship between resource gain and therapy completion: while an increase in gain was related to a decreased chance of completing therapy in men, the opposite effect was noted in women. Conclusions Resource loss has more influence than decisional balance in predicting therapy completion, which can be translated into clinically valid recommendations based on gender differences. PMID- 26813303 TI - Production, Characterization and Evaluation of Kaempferol Nanosuspension for Improving Oral Bioavailability. AB - CONTEXT: Kaempferol has a large particle size and poor water solubility, leading to poor oral bioavailability. The present work aimed to develop a kaempferol nanosuspension (KNS) to improve pharmacokinetics and absolute bioavailability. METHODS: A nanosuspension was prepared using high pressure homogenization (HPH) techniques. The physico-chemical properties of the kaempferol nanosuspension (KNS) were characterized using photon correlation spectroscopy (PCS), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR) and x-ray diffractometry (XRD). A reversephase high performance liquid chromatography (RP-HPLC) method for the analysis of the drug in rat plasma was developed and validated as per ICH guidelines. In vivo pharmacokinetic parameters of oral pure kaempferol solution, oral kaempferol nanosuspension and intravenous pure kaempferol were assessed in rats. RESULTS AND DISCUSSION: The kaempferol nanosuspension had a greatly reduced particle size (426.3 +/- 5.8 nm), compared to that of pure kaempferol (1737 +/- 129 nm). The nanosuspension was stable under refrigerated conditions. No changes in physico-chemical characteristics were observed. In comparison to pure kaempferol, kaempferol nanosuspension exhibited a significantly (P<0.05) increased in Cmax and AUC(0-infinity) following oral administration and a significant improvement in absolute bioavailability (38.17%) compared with 13.03% for pure kaempferol. CONCLUSION: These results demonstrate enhanced oral bioavailability of kaempferol when formulated as a nanosuspension. PMID- 26813302 TI - Pharmaco-Phylogenetic Investigation of Methyl Gallate Isolated from Acacia nilotica (L.) Delile and Its Cytotoxic Effect on NIH3T3 Mouse Fibroblast. AB - Present exploration deals with the therapeutic perspective of methyl gallate isolated from the leaf extract of Acacia nilotica (L.) Delile in contrast to food borne bacterial pathogen's viz., Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium, Pseudomonas aeruginosa and Staphylococcus aureus with their evolutionary succession. The extract was subjected to phytochemical analysis and isolated compound was identified as methyl gallate using UV-vis, IR and NMR spectra. It was found most potent against K. pneumoniae with its minimum inhibition concentration (MIC) of 0.32 mg/ml and minimum bactericidal concentration (MBC) at 0.62 mg/ml. The correlation of MIC values with an evolutionary succession assists the relationship between their genetic and toxic properties. The cytotoxic pursuit of methyl gallate was additionally assessed over NIH3T3 mouse fibroblast by Neutral red (NR) uptake, MTT cell proliferation assay and did not disclose any relevant influence on cell viability as well as cell proliferation. As such, the methyl gallate extracted from the leaf of A. nilotica holds massive antibacterial aptitude and hands out towards a new paradigm for food and pharmaceutical industries. PMID- 26813305 TI - Progress in the Use of Autologous Regenerative Platelet-based Therapies in Implant Dentistry. AB - The field of medicine is rapidly moving towards the development of personalized treatments and non-invasive tools to achieve a more predictable and optimal tissue regeneration. In this sense, the goal of periodontal healing is to arrest disease progression and functionally regenerate all the tissues that comprise the periodontium. The latter implies a well-orchestrated interaction among oral cells, growth factors and extracellular matrix. Although several procedures are performed in an attempt to regenerate lost periodontal tissue, outcomes are not always predictable. Growth factors represent a class of biologically active polypeptides that have a critical role in the healing process. Their use provides a new paradigm to understand the regenerative medicine. The use of platelet- rich plasma (PRP) products as a local source and delivery system of autologous growth factors has emerged recently. Among them, PRGF stands for its remarkable stimulatory effect on oral tissue regeneration, making it a very safe and successful tool with a great value in Dentistry. PMID- 26813304 TI - Controlled Drug Delivery Using Microdevices. AB - Therapeutic drugs administered systematically are evenly distributed to the whole body through blood circulation and have to cross many biological barriers before reaching the pathological site. Conventional drug delivery may make drugs inactive or reduce their potency as they may be hydrolyzed or degraded enzymatically and are rapidly excreted through the urinary system resulting in suboptimal concentration of drugs at the desired site. Controlled drug delivery aims to localize the pharmacological activity of the drug to the desired site at desired release rates. The advances made by micro/nanofluidic technologies have provided new opportunities for better-controlled drug delivery. Various components of a drug delivery system can be integrated within a single tiny micro/nanofluidic chip. This article reviews recent advances of controlled drug delivery made by microfluidic/nanofluidic technologies. We first discuss microreservoir-based drug delivery systems. Then we highlight different kinds of microneedles used for controlled drug delivery, followed with a brief discussion about the current limitations and the future prospects of controlled drug delivery systems. PMID- 26813306 TI - Incretins, Pregnancy, and Gestational Diabetes. AB - The number of pregnant women affected by gestational diabetes mellitus (GDM) is increasing among Caucasians, and East Asians. GDM also increases the risk for later advent of type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease in both women and their offspring. The underlying mechanism of GDM is not fully elucidated. Incretins such as glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic peptide (GIP), have been suggested to have a role in maternal metabolism and weight as well as fetal growth. These hormones might be implicated in mechanisms that compensate for the increment in glycemia and insulin resistance seen during pregnancy, while other factors, such as heredity, environment and lifestyle, but also different race/ethnic background might also lead to the comorbid health problems. Some studies indicate that pregnancy is associated with a diminished GLP-1 response which is more prominently evident in women with GDM and normalizes after delivery. Postprandial GIP level seems to be unaffected by pregnancy, despite its increased level in GDM. On the other hand, the reduced incretin effect observed in GDM may represent a risk factor for obesity, T2DM and metabolic disorders even in the offspring of these women. Further investigations are needed to establish the exact role of incretins in pregnancy and gestational glucose intolerance. PMID- 26813307 TI - An Interplay between Obesity and Inflammation in Gestational Diabetes Mellitus. AB - Gestational diabetes mellitus (GDM) is traditionally defined as hyperglycemia first detected in pregnancy. The risk of GDM is much higher among obese women than in their lean counterparts. An excess of adipose tissue leads to immune and inflammatory responses of both white adipose tissue and the placenta, contributing to systemic inflammation. Although the significance of both obesity and inflammation is relatively well characterized in GDM, the molecular mechanisms involved are not fully defined and require further study. In recent years huge progress has been made in identifying the intracellular signaling pathways involved in the pathophysiology of GDM. However, currently available data regarding inflammation and obesity in women with GDM are still conflicting or incomplete. We discuss selected aspects of the problem and propose future directions for research in the hope of achieving a better understanding of the disease. In particular, this review highlights recent studies exploring molecular alterations related to insulin resistance, inflammation of the adipose tissue and the placenta, lipotoxicity or endotoxemia. PMID- 26813308 TI - Stearoyl-CoA desaturase-1 mediated cell apoptosis in colorectal cancer by promoting ceramide synthesis. AB - Inhibition of stearoyl-CoA desaturase 1 (SCD1) has been found to effectively suppress tumor cell proliferation and induce apoptosis in numerous neoplastic lesions. However, mechanism underlying SCD1-mediated anti-tumor effect has maintained unclear. Herein, we reported endo-lipid messenger ceramides played a critical role in tumor fate modulated by SCD1 inhibition. In vitro study in colorectal cancer cells demonstrated inhibition of SCD1 activity promoted apoptosis attributed to mitochondria dysfunctions, upregulation of reaction oxygen species (ROS), alteration of mitochondrial transmembrane potential and translocation of mitochondrial protein cytochrome C. While these effects were mediated by intracellular ceramide signals through induction of ceramide biosynthesis, rather than exclusive SFA accumulation. In vivo study in xenograft colorectal cancer mice showed pharmacologic administration of SCD1 inhibitor A939 significantly delayed tumor growth, which was reversed by L-cycloserine, an inhibitor of ceramide biosynthesis. These results depicted the cross-talk of SCD1 mediated lipid pathway and endo-ceramide biosynthesis pathway, indicating roles of ceramide signals in SCD1-mediated anti-tumor property. PMID- 26813309 TI - Diagnostic and Surgical Approach of Thyroglossal Duct Cyst in Children: Ten Years Data Review. AB - INTRODUCTION: Thyroglossal duct cysts are the most common congenital midline neck swelling in children. AIM: To evaluate the clinical features, treatment, incidence of complications and outcomes in children with congenital midline neck lesions and more specifically with thyroglossal duct cyst, treated in our department the last ten years. It is a retrospective study. MATERIALS AND METHODS: The aggregated data revealed 59 patients with congenital midline neck lesions, of which 33 patients were with thyroglossal duct cyst (TDC). The diagnosis of TDC was made by physical examination, ultrasound (US) in all cases, and for complicated cases a magnetic resonance imaging (MRI) was performed. In all cases followed histopathological conformation of thyroglossal duct cyst. RESULTS: Fifty nine patients were admitted with midline cystic neck mass and the histopathological evaluation revealed, 33 cases (55.9%) of thyroglossal duct cyst, 14 cases (23.7%) of dermoid cysts, 3 cases (5.1%) of second branchial anomalies, 4 cases (6.7%) of inflammation of unknown cause, 4 cases (6.7%) of lymph nodes and 1 case (1.7%) of capillary skin haemangioma. More specifically, 38 patients were admitted with preoperative diagnosis of thyroglossal duct cyst, but in 5 patients pathological investigation demonstrated the presence of dermoid cyst. The mean age of the 33 patients with TDC at the time of surgery was 6.125 years, ranging between 9 months and 13 years with 10 patients younger than 3 years. Of the 38 patients with initial diagnosis of thyroglossal duct cyst, only four patients (10.5%) had a simple cyst excision and complication rate was 25% (1 case with recurrence). In these patients, the histopathological examination showed that three of them had a dermoid cyst and one had thyroglossal duct cyst. The other 34 patients (89.4%) were treated by Sistrunk's procedure, with two cases (5.9%) were proven on histology to be non TDC. In this group the complication rate was 3.03% (1 case with wound infection). CONCLUSION: The inappropriate surgical approach due to misdiagnosis or the incomplete surgical procedure remains the impact factor for recurrence. The modification of Sistrunk's procedure remains the main surgical technique that can provides good results with low rate of complication (3.03%) and recurrence (0%) as shown of our collecting data. PMID- 26813310 TI - Supernumerary Digits of the Hand. PMID- 26813311 TI - Detection of Free and Protein-Bound ortho-Quinones by Near-Infrared Fluorescence. AB - Aging and oxidative stress are two prominent pathological mechanisms for Parkinson's disease (PD) that are strongly associated with the degeneration of dopamine (DA) neurons in the midbrain. DA and other catechols readily oxidize into highly reactive o-quinone species that are precursors of neuromelanin (NM) pigment and under pathological conditions can modify and damage macromolecules. The role of DA oxidation in PD pathogenesis remains unclear in part due to the lack of appropriate disease models and the absence of a simple method for the quantification of DA-derived oxidants. Here, we describe a rapid, simple, and reproducible method for the quantification of o-quinones in cells and tissues that relies on the near-infrared fluorescent properties of these species. Importantly, we demonstrate that catechol-derived oxidants can be quantified in human neuroblastoma cells and midbrain dopamine neurons derived from induced pluripotent stem cells, providing a novel model to study the downstream actions of o-quinones. This method should facilitate further study of oxidative stress and DA oxidation in PD and related diseases that affect the dopaminergic system. PMID- 26813312 TI - Long-term epidemiological study of disseminated neoplasia of cockles in Galicia (NW Spain): temporal patterns at individual and population levels, influence of environmental and cockle-based factors and lethality. AB - The dynamics of disseminated neoplasia (DN) affecting cockles Cerastoderma edule (L.) in Galicia was addressed at individual and population levels. Early stage of DN was characterized by isolated neoplastic cells occurring in branchial vessels or in the connective tissue of gills, mantle, gonad or digestive gland. As disease progressed, the neoplastic cells appeared loose in foci and became widely distributed throughout the organs. In advanced stages, the connective tissue of most organs was infiltrated by neoplastic cells, which displaced normal cells, leading to the loss of the normal tissue/organ architecture. Host defence reaction was occasionally observed. A field survey performed for 7 years, in two cockle beds located in different Galician Rias, showed that DN is a hyperendemic disease usually present all year-round at high prevalence in adult cockles but with annual prevalence minima in spring likely due to the death of heavily affected cockles, concurrently with gonad ripeness-spawning. DN was detected in the cockles ranging from 10 to 39 mm in size; the highest DN prevalence and severity corresponded to the cockles of intermediate size/age (22-29 mm/0.7-1 year old). Sex did not appear to influence DN occurrence. An inhibitory effect of DN on cockle gametogenesis was detected. PMID- 26813313 TI - Hepatitis C Virus Outbreaks in Hemodialysis Centers: A Continuing Problem. PMID- 26813314 TI - Antimicrobial Stewardship Practices in Michigan Long-Term Care Facilities. PMID- 26813316 TI - Impact of Host Heterogeneity on the Efficacy of Interventions to Reduce Staphylococcus aureus Carriage - CORRIGENDUM. PMID- 26813315 TI - CPE Clearance-A Response to Kim et al. PMID- 26813317 TI - [Drawing experiences from history for inheritance and innovation, a Preface to A Century History of Traditional Chinese Medicine: 1912-2015]. PMID- 26813318 TI - [Basic skeleton and main features of history of traditional Chinese medicine in the last century]. PMID- 26813319 TI - [Textual research on the time of completion of XU Shuwei' books on exo-pathogenic cold diseases]. AB - Shang han bai zheng ge (Poets of Syndromes of Exo-pathogenic Cold Disease), Shang han fa wei lun (Discourse on Elucidation of Exo-pathogenic Cold Disease), Shang han jiu shi lun (90 Discourses on Exo-pathogenic Cold Disease) were the three extant books on exo-pathogenic cold disease written by Xu Shuwei among his other works of its kind. Although there were carved editions of the Yuan and Ming Dynasties, these books were gradually paid attention for citations by other physicians till the Qing Dynasty. Through comparison of its texts, it can be found that the title of Shang han bai zheng ge was mentioned in his other medical works. While Shang han fa wei lun and Shang han jiu shi lun contained some overlapping contents, some even carrying concept contradictory to each other. According to historical materials, Xu Shuwei began to write the above-mentioned 3 books in the Northern Song Dynasty. In the several early years of the Southern Song Dynasty after crossing the Yangtze River, he collected the remained manuscripts and continued to write. Among them, Shang han bai zheng ge was completed first, followed by Shang han fa wei lun, with Shang han jiu shi lun came as the last. PMID- 26813320 TI - [International exchanges in the early stage of the Academy of Traditional Chinese Medicine]. AB - The Academy of Traditional Chinese Medicine under the Ministry of Health was established in 1955. It exerted worldwide influence, and attracted extensive attention internationally. During its early days, lots of letters from abroad asking for TCM consultation were accepted consistently. TCM experts were invited to treat a great number of foreign patients in China or overseas. It also received visits of many foreign government delegations and academic groups. Moreover, physicians were dispatched to visit abroad, international academic conferences were held and training classes were sponsored for returned students and medical interns. Frequent international academic exchanges promoted the friendly intercourse with foreign countries, and the spread of TCM overseas, which displayed the function and value of traditional Chinese medicine, reflecting its unique significance and charm, and its great contributions to the improvement of people's health the world over. PMID- 26813321 TI - [My personal idea on acupuncture and moxibustion (acu-moxibustion) literature of the Republic of China not recorded in the General Catalog of the Ancient Chinese Medical Books]. AB - In addition to the collected books in the General Catalog of Ancient Chinese Medical Books, there are lots of acu-moxibustion literature of the Republic of China period scattered among the people which are not carried in this Catalog, some of them are rare and precious ones. In 1933, the first issue of Acu moxibustion Journal was published and became the first professional Journal of acupuncture and moxibustion in China, 35 issues were published at that time, with many monographs on acu-moxibustion carried in its "special column". Meanwhile, other acupuncturists from different regions also established acu-moxibustion associations or schools and edited all kinds of acupuncture moxibustion teaching materials in order to develop acu-moxibustion education. In a word, the acu moxibustion literature of the Republic of China were not only rich in forms and contents, but also combined with regional characteristics. Therefore, it should be pay more attention on that field and do further study. PMID- 26813322 TI - [A proposal for the works of traditional Chinese medicine drafted by Mr. Yue Meizhong]. AB - In 1951, The Interim Regulations on Practitioners of Traditional Chinese Medicine was issued by the Ministry of Health to restrict the practitioners' practice of traditional Chinese medicine (TCM) and to transform TCM, resulting in TCM facing the risk of interrupting its inheritance and development. In 1953, Yue Meizhong, a famous TCM physician, drafted a proposal about TCM development. After discussing and revising with Li Zhensan, the Director of North China Institute of TCM Experiment, the proposal was submitted to the Central Committee of Chinese Communist Party and Government Administration Council as a reference. The proposal made a retrospect of the long history of TCM development, elaborated the characteristic and significance of TCM, proposed the detailed suggestions about the establishment of TCM administration institutions at various levels, set up of TCM Academy and Colleges etc., which represented the voice of TCM professionals, and reflected the objective principle of TCM development. PMID- 26813323 TI - [The inaugural meeting of Academy of Traditional Chinese Medicine, a milestone in the career of TCM in New China]. AB - On 19 October, 1955, the Founding Congress of Academy of Traditional Chinese Medicine was held at the Academy Hall located at Beixiange, Guang'anmen Nei, Beijing. The main issues of the Congress include: the report of Academy's preparatory process, speeches delivered by leading comrades, announcement of Academy's leading group, awards granting, and speeches of the guests. Nowadays, by reviewing the past 60 years, the high attention to the TCM career paid by the Party and people's government still can be sensed. It could be said that the establishment of Academy of Traditional Chinese Medicine is a milestone of TCM career in New China. PMID- 26813324 TI - [The first national Whole-time Training Class for Western Physicians Learning Traditional Chinese Medicine in China]. AB - On 19 October, 1955, at the time when the Academy of Traditional Chinese Medicine affiliated with the Ministry of Health was established, the opening ceremony of the first Whole-time Training Class for Western Physicians Learning Systematically Traditional Chinese Medicine was also held. Altogether 84 new graduates from western medical colleges and skilled doctors of western medicine from all over the country were registered. During the 2.5 year term of training, the students learnt 16 professional courses and then practiced at the clinic, and graduated with gratifying results in July, 1958. On 11 October the same year, Chairman Mao made an important instruction to the report submitted by the Leading Party Group of the Ministry of Health, "A Report to the Party Central Committee about the situation, results and experience of Whole-time Training Class for Western Physicians Learning Traditional Chinese Medicine", by pointing out that "in the future, the Training Class for Western Physicians Learning Traditional Chinese Medicine should be held across the country hereafter. This is a top issue and is not to be ignored". PMID- 26813325 TI - [Brief history of the main institutions in the China Academy of Chinese Medical Sciences]. AB - On 19 October, 1955, the Academy of Traditional Chinese Medicine affiliated with the Ministry of Health of the People's Republic of China was established formally. On 8 October, 1985, its name was changed to "China Academy of Traditional Chinese Medicine", which was renamed as "China Academy of Chinese Medical Sciences (CACMS)" on 15 November, 2005. During its six decades of history, the construction of the institutions in the CACMS were improved constantly. Nowadays, there are altogether 17 academic institutions, 6 clinical institutions, 1 educational institution and 6 industrial institutions in the CACMS, which has become a comprehensive research institution of traditional Chinese medicine (TCM), embodying scientific research, clinical service, education and industry as a whole, under the direct control of the State Administration of Traditional Chinese Medicine of the People's Republic of China. PMID- 26813326 TI - Wavelength-tunable entangled photons from silicon-integrated III-V quantum dots. AB - Many of the quantum information applications rely on indistinguishable sources of polarization-entangled photons. Semiconductor quantum dots are among the leading candidates for a deterministic entangled photon source; however, due to their random growth nature, it is impossible to find different quantum dots emitting entangled photons with identical wavelengths. The wavelength tunability has therefore become a fundamental requirement for a number of envisioned applications, for example, nesting different dots via the entanglement swapping and interfacing dots with cavities/atoms. Here we report the generation of wavelength-tunable entangled photons from on-chip integrated InAs/GaAs quantum dots. With a novel anisotropic strain engineering technique based on PMN PT/silicon micro-electromechanical system, we can recover the quantum dot electronic symmetry at different exciton emission wavelengths. Together with a footprint of several hundred microns, our device facilitates the scalable integration of indistinguishable entangled photon sources on-chip, and therefore removes a major stumbling block to the quantum-dot-based solid-state quantum information platforms. PMID- 26813329 TI - Design, Synthesis and Biological Evaluation of New Thieno[2,3- d]pyrimidines as Anti-inflammatory Agents. AB - BACKGROUND: Long term use of NSAIDS is mainly accompanied by major health implications such as gastrointestinal erosions, ulcerations and nephrotoxicity. These side effects arise from local irritation by the carboxylic acid moiety, that is common to most of NSAIDs (topical effect), in addition to decreased cytoprotective prostaglandin production. Therefore, in the medicinal chemistry research area, there is an ongoing need for the discovery of new, potent and safer anti-inflammatory lead compounds devoid of the irritant carboxylic acid moiety. METHODS: A series of new 3-substituted-2-thioxo-thieno[2,3-d]pyrimidine derivatives were synthesized through reacting the starting 3-amino-2-thioxo thieno[2,3-d]pyrimidines with different aromatic aldehydes. The structure of all newly synthesized compounds was confirmed with spectral and elemental analyses. The synthesized thieno[2,3-d]pyrimidines were investigated for in vivo anti inflammatory activity, using the carrageenan induced paw edema test. The possible antiinflammatory mechanism was also evaluated by determining the concentration of prostaglandin E2 (PGE2) in blood serum using a rat specific PGE2 ELISA kit. RESULTS: All test compounds could significantly reduce carrageenan induced paw edema comparable to diclofenac sodium as a potent anti-inflammatory drug. Moreover, they could decrease the concentration of PGE2 in blood serum. Interestingly, compound 4c exhibited the most potent in vivo anti-inflammatory activity with protection of 35%, 36% and 42% against carrageenan-induced paw edema after 1h, 2h and 3h, representing 92%, 86% and 88% respectively of diclofenac activity. It also decreased the concentration of PGE2 in blood serum to 19 pg/ mL which is comparable to diclofenac with PGE2 concentration of 12 pg/ mL. Moreover, Compounds 4f, 4a, 4i and 4e exerted significant anti-inflammatory activity after 4h, representing 71%, 69%, 63% and 61% respectively of diclofenac activity. Furthermore, they significantly decreased the concentration of PGE2 in blood serum. CONCLUSION: These thienopyrimidines may be used as good candidates for the search of promising, potent and safe antiinflammatory leads for being free from acidic functions. PMID- 26813330 TI - Experience with dynamic reinforcement rates decreases resistance to extinction. AB - The ability of organisms to detect reinforcer-rate changes in choice preparations is positively related to two factors: the magnitude of the change in rate and the frequency with which rates change. Gallistel (2012) suggested similar rate detection processes are responsible for decreases in responding during operant extinction. Although effects of magnitude of change in reinforcer rate on resistance to extinction are well known (e.g., the partial-reinforcement extinction effect), effects of frequency of changes in rate prior to extinction are unknown. Thus, the present experiments examined whether frequency of changes in baseline reinforcer rates impacts resistance to extinction. Pigeons pecked keys for variable-interval food under conditions where reinforcer rates were stable and where they changed within and between sessions. Overall reinforcer rates between conditions were controlled. In Experiment 1, resistance to extinction was lower following exposure to dynamic reinforcement schedules than to static schedules. Experiment 2 showed that resistance to presession feeding, a disruptor that should not involve change-detection processes, was unaffected by baseline-schedule dynamics. These findings are consistent with the suggestion that change detection contributes to extinction. We discuss implications of change-detection processes for extinction of simple and discriminated operant behavior and relate these processes to the behavioral-momentum based approach to understanding extinction. PMID- 26813331 TI - High-Efficiency Perovskite Solar Cells Employing a S,N-Heteropentacene-based D-A Hole-Transport Material. AB - We developed a new donor-pi-acceptor-type hole-transport material (HTMs) incorporating S,N-heteropentacene as pi-spacer, triarylamine as donor, and dicyanovinylene as acceptor. In addition to appropriate frontier molecular orbital energies, the new HTM showed high photo absorptivity in the visible region. Without the use of p-dopants, solution-processed mixed perovskite devices using the HTM achieved power conversion efficiencies of up to 16.9% and high photocurrents of up to 22.2 mA cm(-2). These results demonstrate that heteroacene can be an excellent building block to prepare alternative HTMs for perovskite solar cells and hold promise for further advancement through fine-tuning the molecular structure. PMID- 26813332 TI - Differential contributions of porcine bocavirus NP1 protein N- and C-terminal regions to its nuclear localization and immune regulation. AB - Porcine bocavirus (PBoV), a newly identified parvovirus in the family Parvoviridae, has been reported worldwide in swine with post-weaning multisystemic wasting syndrome, respiratory disease or diarrhoea and in asymptomatic swine. NP1 is a protein unique to the genus Bocavirus and its function is not fully understood. In this study, we show that the N-terminal region of PBoV NP1 contains two classical nuclear localization signals (cNLSs) and a non-classical NLS. The N-terminal region also inhibits the promoter activity of IFN-beta and IFN-stimulated response element activity the same as full-length NP1 protein, but the PBoV NP1 C-terminal region does not. PBoV NP1 also induces NFkappaB activation by increasing the phosphorylation of p65, and we demonstrate that the C-terminal region (aa 168-218) is responsible for the induction of NFkappaB, although the cNLS region of NP1 enhances this activation. The data suggest that PBoV NP1 contains two functionally independent domains in its N- and C-terminal regions. Thus, the N-terminal region of PBoV NP1 is critical for its nuclear localization and IFN-related promoter inhibition, and the C-terminal region is critical for its induction of NFkappaB. PMID- 26813333 TI - Large scale patterns in vertical distribution and behaviour of mesopelagic scattering layers. AB - Recent studies suggest that previous estimates of mesopelagic biomasses are severely biased, with the new, higher estimates underlining the need to unveil behaviourally mediated coupling between shallow and deep ocean habitats. We analysed vertical distribution and diel vertical migration (DVM) of mesopelagic acoustic scattering layers (SLs) recorded at 38 kHz across oceanographic regimes encountered during the circumglobal Malaspina expedition. Mesopelagic SLs were observed in all areas covered, but vertical distributions and DVM patterns varied markedly. The distribution of mesopelagic backscatter was deepest in the southern Indian Ocean (weighted mean daytime depth: WMD 590 m) and shallowest at the oxygen minimum zone in the eastern Pacific (WMD 350 m). DVM was evident in all areas covered, on average ~50% of mesopelagic backscatter made daily excursions from mesopelagic depths to shallow waters. There were marked differences in migrating proportions between the regions, ranging from ~20% in the Indian Ocean to ~90% in the Eastern Pacific. Overall the data suggest strong spatial gradients in mesopelagic DVM patterns, with implied ecological and biogeochemical consequences. Our results suggest that parts of this spatial variability can be explained by horizontal patterns in physical-chemical properties of water masses, such as oxygen, temperature and turbidity. PMID- 26813334 TI - Systems-Pharmacology Dissection of Traditional Chinese Medicine Compound Saffron Formula Reveals Multi-scale Treatment Strategy for Cardiovascular Diseases. AB - Cardiovascular diseases (CVDs) have been regarding as "the world's first killer" of human beings in recent years owing to the striking morbidity and mortality, the involved molecular mechanisms are extremely complex and remain unclear. Traditional Chinese medicine (TCM) adheres to the aim of combating complex diseases from an integrative and holistic point of view, which has shown effectiveness in CVDs therapy. However, system-level understanding of such a mechanism of multi-scale treatment strategy for CVDs is still difficult. Here, we developed a system pharmacology approach with the purpose of revealing the underlying molecular mechanisms exemplified by a famous compound saffron formula (CSF) in treating CVDs. First, by systems ADME analysis combined with drug targeting process, 103 potential active components and their corresponding 219 direct targets were retrieved and some key interactions were further experimentally validated. Based on this, the network relationships among active components, targets and diseases were further built to uncover the pharmacological actions of the drug. Finally, a "CVDs pathway" consisted of several regulatory modules was incorporated to dissect the therapeutic effects of CSF in different pathological features-relevant biological processes. All this demonstrates CSF has multi-scale curative activity in regulating CVD-related biological processes, which provides a new potential way for modern medicine in the treatment of complex diseases. PMID- 26813335 TI - Atomic-layer soft plasma etching of MoS2. AB - Transition from multi-layer to monolayer and sub-monolayer thickness leads to the many exotic properties and distinctive applications of two-dimensional (2D) MoS2. This transition requires atomic-layer-precision thinning of bulk MoS2 without damaging the remaining layers, which presently remains elusive. Here we report a soft, selective and high-throughput atomic-layer-precision etching of MoS2 in SF6 + N2 plasmas with low-energy (<0.4 eV) electrons and minimized ion-bombardment related damage. Equal numbers of MoS2 layers are removed uniformly across domains with vastly different initial thickness, without affecting the underlying SiO2 substrate and the remaining MoS2 layers. The etching rates can be tuned to achieve complete MoS2 removal and any desired number of MoS2 layers including monolayer. Layer-dependent vibrational and photoluminescence spectra of the etched MoS2 are also demonstrated. This soft plasma etching technique is versatile, scalable, compatible with the semiconductor manufacturing processes, and may be applicable for a broader range of 2D materials and intended device applications. PMID- 26813336 TI - G-LoSA: An efficient computational tool for local structure-centric biological studies and drug design. AB - Molecular recognition by protein mostly occurs in a local region on the protein surface. Thus, an efficient computational method for accurate characterization of protein local structural conservation is necessary to better understand biology and drug design. We present a novel local structure alignment tool, G-LoSA. G LoSA aligns protein local structures in a sequence order independent way and provides a GA-score, a chemical feature-based and size-independent structure similarity score. Our benchmark validation shows the robust performance of G-LoSA to the local structures of diverse sizes and characteristics, demonstrating its universal applicability to local structure-centric comparative biology studies. In particular, G-LoSA is highly effective in detecting conserved local regions on the entire surface of a given protein. In addition, the applications of G-LoSA to identifying template ligands and predicting ligand and protein binding sites illustrate its strong potential for computer-aided drug design. We hope that G LoSA can be a useful computational method for exploring interesting biological problems through large-scale comparison of protein local structures and facilitating drug discovery research and development. G-LoSA is freely available to academic users at http://im.compbio.ku.edu/GLoSA/. PMID- 26813338 TI - In silico analysis of the effect of mutation on epidermal growth factor receptor in non-small-cell lung carcinoma: from mutational analysis to drug designing. AB - Tyrosine kinase inhibitors (TKI)-resistant mutation in epidermal growth factor receptor's (EGFR) kinase domain is an important anomaly to look into. Studying the mutations at atomic level using molecular dynamics simulations gave us an insight into the architectural changes happening at the microscopic level. The knowledge was used to design new TKI whose function is devoid of the affect of the mutations in kinase domain. Traditional Chinese medicinal library was used for structure-based drug designing, where virtual screening was followed by ADME/Tox analysis and the shortlisted compounds were docked into the kinase domain of EGFR and simulated there using atomic-level selection of the grid. The shortlisted compounds from molecular docking analysis were subjected to MM-PBSA calculations. The in silico data generated is giving a strong lead compound for further in vitro and in vivo analysis. PMID- 26813337 TI - Effects of selective serotonin and norepinephrine reuptake inhibitors on depressive- and impulsive-like behaviors and on monoamine transmission in experimental temporal lobe epilepsy. AB - OBJECTIVE: Examine therapeutic potential of a selective serotonin reuptake inhibitor (SSRI) and a norepinephrine reuptake inhibitor (NERI) in an animal model of comorbidity between epilepsy, depression-like, and impulsive-like impairments. METHODS: Epilepsy was induced in male Wistar rats by LiCl and pilocarpine. An SSRI fluoxetine (FLX), and an NERI reboxetine (RBX) were administered either alone or as a combination over 1 week. Depressive-like and impulsive-like behaviors were examined using the forced swim test. Fast scan cyclic voltammetry was used to analyze serotonergic transmission in the raphe nucleus (RN)-prefrontal cortex (PFC) pathway, and noradrenergic transmission in locus coeruleus (LC)-PFC, and LC-RN projections. Monoamine levels in PFC were measured using high-performance liquid chromatography (HPLC). Functional capacities of 5-HT1A receptors and alpha2A adrenoreceptors in PFC were analyzed by autoradiography. RESULTS: Epileptic rats showed behavioral signs of depression and hyperimpulsivity, suppressed serotonergic and noradrenergic tones, decreased levels of serotonin (5-HT), and norepinephrine (NE); 5-HT1A receptor and alpha2A adrenoreceptors functions remained intact. FLX failed to improve behavioral deficits, but effectively raised 5-HT level and marginally improved RN-PFC serotonergic transmission. RBX reversed impulsive-like behavior, normalized content of NE and noradrenergic tone in LC-PFC and LC-RN. FLX-RBX combination fully reversed depressive-like behavior, and normalized RN-PFC serotonergic transmission. None of the treatment modified the function of 5-HT and NE receptors. SIGNIFICANCE: Depressive- and impulsive-like behaviors in the pilocarpine model of epilepsy stem respectively from dysfunctions of serotonergic and noradrenergic ascending pathways. At the same time, epilepsy-associated depression is SSRI resistant. The finding that an SSRI-NERI combination exerts antidepressant effect, along with RBX-induced improvement of LC-RN noradrenergic transmission point toward the involvement of LC-RN noradrenergic input in enabling therapeutic potential of FLX. Medications that improve serotonergic and noradrenergic transmission, such as serotonin-norepinephrine reuptake inhibitors may be effective in treating epilepsy-associated SSRI-resistant depression, as well as concurrent depression and attention-deficit/hyperactivity disorder (ADHD). PMID- 26813339 TI - The goblet cell-derived mediator RELM-beta drives spontaneous colitis in Muc2 deficient mice by promoting commensal microbial dysbiosis. AB - Intestinal goblet cells are potentially key players in controlling susceptibility to ulcerative colitis (UC). Although impaired mucin (Muc2) production by goblet cells increases microbial stimulation of the colonic mucosa, goblet cells secrete other mediators that may influence or promote UC development. Correspondingly, Muc2-deficient ((-/-)) mice develop spontaneous colitis, concurrent with the dramatic upregulation of the goblet cell mediator, resistin-like molecule-beta (RELM-beta). Testing RELM-beta's role, we generated Muc2(-/-)/Retnlb(-/-) mice, finding that RELM-beta deficiency significantly attenuated colitis development and symptoms compared with Muc2(-/-) mice. RELM-beta expression in Muc2(-/-) mice strongly induced the production/secretion of the antimicrobial lectin RegIIIbeta, that exerted its microbicidal effect predominantly on Gram-positive Lactobacillus species. Compared with Muc2(-/-)/Retnlb(-/-) mice, this worsened intestinal microbial dysbiosis with a selective loss of colonic Lactobacilli spp. in Muc2(-/ ) mice. Orally replenishing Muc2(-/-) mice with murine Lactobacillus spp., but not with a probiotic formulation containing several human Lactobacillus spp. (VSL#3), ameliorated their spontaneous colitis in concert with increased production of short-chain fatty acids. These studies demonstrate that the goblet cell mediator RELM-beta drives colitis in Muc2(-/-) mice by depleting protective commensal microbes. The ability of selective commensal microbial replacement to ameliorate colitis suggests that personalized bacterial therapy may prove beneficial for treatment of UC. PMID- 26813340 TI - Distinct genital tract HIV-specific antibody profiles associated with tenofovir gel. AB - The impact of topical antiretrovirals for pre-exposure prophylaxis on humoral responses following HIV infection is unknown. Using a binding antibody multiplex assay, we investigated HIV-specific IgG and IgA responses to envelope glycoproteins, p24 Gag and p66, in the genital tract (GT) and plasma following HIV acquisition in women assigned to tenofovir gel (n=24) and placebo gel (n=24) in the CAPRISA 004 microbicide trial to assess if this topical antiretroviral had an impact on mucosal and systemic antibody responses. Linear mixed effect modeling and partial least squares discriminant analysis was used to identify multivariate antibody signatures associated with tenofovir use. There were significantly higher response rates to gp120 Env (P=0.03), p24 (P=0.002), and p66 (P=0.009) in plasma and GT in women assigned to tenofovir than placebo gel at multiple time points post infection. Notably, p66 IgA titers in the GT and plasma were significantly higher in the tenofovir compared with the placebo arm (P<0.05). Plasma titers for 9 of the 10 HIV-IgG specificities predicted GT levels. Taken together, these data suggest that humoral immune responses are increased in blood and GT of individuals who acquire HIV infection in the presence of tenofovir gel. PMID- 26813342 TI - Signal transducer and activator of transcription-3 licenses Toll-like receptor 4 dependent interleukin (IL)-6 and IL-8 production via IL-6 receptor-positive feedback in endometrial cells. AB - Interleukin 6 (IL-6), acting via the IL-6 receptor (IL6R) and signal transducer and activator of transcription-3 (STAT3), limits neutrophil recruitment once bacterial infections are resolved. Bovine endometritis is an exemplar mucosal disease, characterized by sustained neutrophil infiltration and elevated IL-6 and IL-8, a neutrophil chemoattractant, following postpartum Gram-negative bacterial infection. The present study examined the impact of the IL6R/STAT3 signaling pathway on IL-8 production by primary endometrial cells in response to short- or long-term exposure to lipopolysaccharide (LPS) from Gram-negative bacteria. Tyrosine phosphorylation of STAT3 is required for DNA binding and expression of specific targets genes. Immunoblotting indicated constitutive tyrosine phosphorylation of STAT3 in endometrial cells was impeded by acute exposure to LPS. After 24 h exposure to LPS, STAT3 returned to a tyrosine phosphorylated state, indicating cross-talk between the Toll-like receptor 4 (TLR4) and the IL6R/STAT3 signaling pathways. This was confirmed by short interfering RNA targeting the IL6R, which abrogated the accumulation of IL-6 and IL-8, induced by LPS. Furthermore, there was a differential endometrial cell response, as the accumulation of IL-6 and IL-8 was dependent on STAT3, suppressor of cytokine signaling 3, and Src kinase signaling in stromal cells, but not epithelial cells. In conclusion, positive feedback through the IL6R amplifies LPS-induced IL-6 and IL-8 production in the endometrium. These findings provide a mechanistic insight into how elevated IL-6 concentrations in the postpartum endometrium during bacterial infection leads to marked and sustained neutrophil infiltration. PMID- 26813341 TI - Novel strategies for targeting innate immune responses to influenza. AB - We previously reported that TLR4(-/-) mice are refractory to mouse-adapted A/PR/8/34 (PR8) influenza-induced lethality and that therapeutic administration of the TLR4 antagonist Eritoran blocked PR8-induced lethality and acute lung injury (ALI) when given starting 2 days post infection. Herein we extend these findings: anti-TLR4- or -TLR2-specific IgG therapy also conferred significant protection of wild-type (WT) mice from lethal PR8 infection. If treatment is initiated 3 h before PR8 infection and continued daily for 4 days, Eritoran failed to protect WT and TLR4(-/-) mice, implying that Eritoran must block a virus-induced, non-TLR4 signal that is required for protection. Mechanistically, we determined that (i) Eritoran blocks high-mobility group B1 (HMGB1)-mediated, TLR4-dependent signaling in vitro and circulating HMGB1 in vivo, and an HMGB1 inhibitor protects against PR8; (ii) Eritoran inhibits pulmonary lung edema associated with ALI; (iii) interleukin (IL)-1beta contributes significantly to PR8-induced lethality, as evidenced by partial protection by IL-1 receptor antagonist (IL-1Ra) therapy. Synergistic protection against PR8-induced lethality was achieved when Eritoran and the antiviral drug oseltamivir were administered starting 4 days post infection. Eritoran treatment does not prevent development of an adaptive immune response to subsequent PR8 challenge. Overall, our data support the potential of a host-targeted therapeutic approach to influenza infection. PMID- 26813344 TI - IL-36alpha expression is elevated in ulcerative colitis and promotes colonic inflammation. AB - A role for the IL-36 family of cytokines has been identified in the pathogenesis of psoriasis. Although significant mechanistic overlap can exist between psoriasis and inflammatory bowel disease (IBD), to date there have been no reports investigating the IL-36 family in gastrointestinal inflammation. Here we demonstrate that expression levels of IL-36alpha are specifically elevated in the colonic mucosa of ulcerative colitis patients. This elevated expression is mirrored in the inflamed colonic mucosa of mice, wherein IL-36 receptor deficiency confirmed this pathway as a mediator of mucosal inflammation. Il36r-/- mice exhibited reduced disease severity in an acute DSS-induced model of colitis in association with decreased innate inflammatory cell infiltration to the colon lamina propria. Consistent with these data, infection with the enteropathogenic bacteria Citrobacter rodentium, resulted in reduced innate inflammatory cell recruitment and increased bacterial colonization in the colons of il36r-/- mice. Il36r-/- mice also exhibited altered T helper cell responses in this model, with enhanced Th17 and reduced Th1 responses, demonstrating that IL-36R signaling also regulates intestinal mucosal T-cell responses. These data identify a novel role for IL-36 signaling in colonic inflammation and indicate that the IL-36R pathway may represent a novel target for therapeutic intervention in IBD. PMID- 26813343 TI - Protein tyrosine phosphatase 1B negatively regulates S100A9-mediated lung damage during respiratory syncytial virus exacerbations. AB - Protein tyrosine phosphatase 1B (PTP1B) has anti-inflammatory potential but PTP1B responses are desensitized in the lung by prolonged cigarette smoke exposure. Here we investigate whether PTP1B expression affects lung disease severity during respiratory syncytial viral (RSV) exacerbations of chronic obstructive pulmonary disease (COPD). Ptp1b(-/-) mice infected with RSV exhibit exaggerated immune cell infiltration, damaged epithelial cell barriers, cytokine production, and increased apoptosis. Elevated expression of S100A9, a damage-associated molecular pattern molecule, was observed in the lungs of Ptp1b(-/-) mice during RSV infection. Utilizing a neutralizing anti-S100A9 IgG antibody, it was determined that extracellular S100A9 signaling significantly affects lung damage during RSV infection. Preexposure to cigarette smoke desensitized PTP1B activity that coincided with enhanced S100A9 secretion and inflammation in wild-type animals during RSV infection. S100A9 levels in human bronchoalveolar lavage fluid had an inverse relationship with lung function in healthy subjects, smokers, and COPD subjects. Fully differentiated human bronchial epithelial cells isolated from COPD donors cultured at the air liquid interface secreted more S100A9 than cells from healthy donors or smokers following RSV infection. Together, these findings show that reduced PTP1B responses contribute to disease symptoms in part by enhancing S100A9 expression during viral-associated COPD exacerbations. PMID- 26813348 TI - Oceanic barnacles act as foundation species on plastic debris: implications for marine dispersal. AB - Plastic has emerged as an abundant, stable substratum for oceanic dispersal of organisms via rafting. However, the ecological mechanisms underlying community diversity on plastic debris remain poorly understood. On a cruise from California to Hawai'i, we surveyed plastic debris, some likely originating from the 2011 Tohoku tsunami, to examine the relationship between rafting community diversity and both habitat area and stalked barnacle (Lepas spp.) abundance. For sessile taxa richness, we observed an interaction in which the positive effect of debris area weakened the negative effect of barnacle cover. In contrast, for mobile taxa richness, including cohabiting species from opposite sides of the Pacific Ocean, barnacle abundance had a positive effect that was strongest at smaller debris sizes. These findings suggest that barnacles, through interactions with habitat area, have trait-dependent effects on other species, serving as both foundation species and competitors, mediating the diversity and dispersal potential of marine organisms on plastic debris. PMID- 26813346 TI - CD101 inhibits the expansion of colitogenic T cells. AB - CD101 exerts negative-costimulatory effects in vitro, but its function in vivo remains poorly defined. CD101 is abundantly expressed on lymphoid and myeloid cells in intestinal tissues, but absent from naive splenic T cells. Here, we assessed the impact of CD101 on the course of inflammatory bowel disease (IBD). Using a T-cell transfer model of chronic colitis, we found that in recipients of naive T cells from CD101(+/+) donors up to 30% of the recovered lymphocytes expressed CD101, correlating with an increased interleukin (IL)-2-mediated FoxP3 expression. Transfer of CD101(-/-) T cells caused more severe colitis and was associated with an expansion of IL-17-producing T cells and an enhanced expression of IL-2Ralpha/beta independently of FoxP3. The co-transfer of naive and regulatory T cells (Treg) protected most effectively from colitis, when both donor and recipient mice expressed CD101. Although the expression of CD101 on T cells was sufficient for Treg-function and the inhibition of T-cell proliferation, sustained IL-10 production required additional CD101 expression by myeloid cells. Finally, in patients with IBD a reduced CD101 expression on peripheral and intestinal monocytes and CD4(+) T cells correlated with enhanced IL-17 production and disease activity. Thus, CD101 deficiency is a novel marker for progressive colitis and potential target for therapeutic intervention. PMID- 26813345 TI - Translational opportunities for targeting the Th17 axis in acute graft-vs.-host disease. AB - Allogeneic stem cell transplantation (allo-SCT) is a curative therapy for different life-threatening malignant and non-malignant hematologic disorders. Acute graft-vs.-host disease (aGVHD) and particularly gastrointestinal aGVHD remains a major source of morbidity and mortality following allo-SCT, which limits the use of this treatment in a broader spectrum of patients. Better understanding of aGVHD pathophysiology is indispensable to identify new therapeutic targets for aGVHD prevention and therapy. Growing amount of data suggest a role for T helper (Th)17 cells in aGVHD pathophysiology. In this review, we will discuss the current knowledge in this area in animal models and in humans. We will then describe new potential treatments for aGVHD along the Th17 axis. PMID- 26813347 TI - Nucleotide-binding oligomerization domain 1 acts in concert with the cholecystokinin receptor agonist, cerulein, to induce IL-33-dependent chronic pancreatitis. AB - Nucleotide-binding oligomerization domain 1 (NOD1) fulfills important host defense functions via its responses to a variety of gut pathogens. Recently, however, we showed that in acute pancreatitis caused by administration of cholecystokinin receptor (CCKR) agonist (cerulein) NOD1 also has a role in inflammation via its responses to gut commensal organisms. In the present study, we explored the long-term outcome of such NOD1 responsiveness in a new model of chronic pancreatitis induced by repeated administration of low doses of cerulein in combination with NOD1 ligand. We found that the development of chronic pancreatitis in this model requires intact NOD1 and type I IFN signaling and that such signaling mediates a macrophage-mediated inflammatory response that supports interleukin (IL)-33 production by acinar cells. The IL-33, in turn, has a necessary role in the induction of IL-13 and TGF-beta1, factors causing the fibrotic reaction characteristic of chronic pancreatitis. Interestingly, the Th2 effects of IL-33 were attenuated by the concomitant type I IFN response since the inflammation was marked by clear increases in IFN-gamma and TNF-alpha production but only marginal increases in IL-4 production. These studies establish chronic pancreatitis as an IL-33-dependent inflammation resulting from synergistic interactions between the NOD1 and CCKR signaling pathways. PMID- 26813349 TI - Adjunctive maneuvers to treat urethral stricture: a review of the world literature. AB - The development of urethral stricture (US) or bladder neck contracture is a relatively uncommon but well described condition observed primarily in men. Despite familiarity with US disease, management remains challenging for urologists. Risk factors for the development of USs or bladder neck contracture include primary treatment modality, tobacco smoking, coronary artery disease and poorly controlled diabetes mellitus. Numerous treatment options exist for this condition that vary in procedural complexity, including intermittent self catheterization (CIC), serial urethral dilation, endoscopic techniques and open reconstructive repairs. Repetitive procedures for this condition may carry increased failure rates and morbidities. For the treatment of refractory or recalcitrant bladder neck contracture, newer intralesional anti-proliferative, anti-scar agents have been used in combination with transurethral bladder neck incisions to augment outcome and long-term effect. The primary focus of this systematic review of the published literature is to streamline and summarize various and newer therapeutic modalities available to manage patients with US or bladder neck contracture. PMID- 26813351 TI - Evaluation of the psychometric properties of the Persian version of the Pittsburgh Sleep Quality Index in depressed patients. AB - INTRODUCTION: The Pittsburgh Sleep Quality Questionnaire is capable of covering different stages of sleep, and it is regarded as one of the best ones available, and checking for its validity and reliability among depressed patients is a step in this direction. The aim of this study was to evaluate the reliability and validity of the Persian version of the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) questionnaires in patients with depression. METHODS: In this study, 93 depressed patients were in the study group, and 100 patients were in the control group. The Persian translation of the PSQI and ESS questionnaires and the Beck Depression Inventory (BDI) were at the disposal of both validity and reliability of PSQI and ESS, and its correlation with BDI scores were analyzed. RESULTS: In our study, Cronbach's alpha coefficient of the PSQI questionnaire was 0.821. According to the PSQI and BDI-II scores, the results between the PSQI and ESS scores were significantly correlated. CONCLUSION: Using the Persian PSQI and ESS questionnaires to evaluate sleep quality and daytime sleepiness in patients with depression provides a reliable and valid measure for subjective sleep quality in clinical practice and research. PMID- 26813350 TI - ADAR-mediated RNA editing suppresses sleep by acting as a brake on glutamatergic synaptic plasticity. AB - It has been postulated that synaptic potentiation during waking is offset by a homoeostatic reduction in net synaptic strength during sleep. However, molecular mechanisms to support such a process are lacking. Here we demonstrate that deficiencies in the RNA-editing gene Adar increase sleep due to synaptic dysfunction in glutamatergic neurons in Drosophila. Specifically, the vesicular glutamate transporter is upregulated, leading to over-activation of NMDA receptors, and the reserve pool of glutamatergic synaptic vesicles is selectively expanded in Adar mutants. Collectively these changes lead to sustained neurotransmitter release under conditions that would otherwise result in synaptic depression. We propose that a shift in the balance from synaptic depression towards synaptic potentiation in sleep-promoting neurons underlies the increased sleep pressure of Adar-deficient animals. Our findings provide a plausible molecular mechanism linking sleep and synaptic plasticity. PMID- 26813353 TI - The highest (3600 IU) reported overdose of insulin glargine ever and management. PMID- 26813352 TI - Rare case of primary pleural lymphoma presenting with pleural effusion. AB - Primary pleural lymphoma is rare and has been described in association with human immunodeficiency virus (HIV) infection or pyothorax. We report a rare case of primary pleural lymphoma in a 73-year-old man who presented with chest pain and no history of HIV infection or pyothorax. Chest imaging showed pleural thickening and pleural effusion. Thoracoscopic pleural biopsy was performed. Histopathological and immunohistochemical examinations conformed to that of a diffuse large B-cell lymphoma. Physicians should be aware of this rare location of primary lymphoma and implement thoracoscopy as soon as possible. PMID- 26813355 TI - Commentary on Moodley S et al. "Shouldn't Propranolol be Used to Treat All Hemangiomas?" and Dr. Blei's Invited Commentary. PMID- 26813354 TI - When to ask male adolescents to provide semen sample for fertility preservation? AB - BACKGROUND: Fertility preservation in adolescents undergoing sterilizing radiation and/or chemotherapy is the standard of care in oncology. The opportunity for patients to provide a semen sample by ejaculation is a critical issue in adolescent fertility preservation. METHODS: Fifty males with no medical or sexual developmental abnormalities were evaluated. The subjects were screened for evidence of orgasmic, erectile, and ejaculatory dysfunction. A detailed sexual development history was obtained under an Institutional Review Board (IRB) approved protocol. RESULTS: Fifty males, aged 18-65 years (mean 39+/-16.03 years) volunteered to be part of this study. The mean reported age for the onset of puberty was 12.39 years (95% CI, 11.99-12.80 years), 13.59 years (95% CI, 13.05 14.12 years) for the first ejaculation, 12.56 years (95% CI, 11.80-13.32 years) for the start of masturbation, and 17.26 years (95% CI, 16.18-18.33 years) for the first experienced intercourse. Seventy-five percent of the cohort reached puberty by the age of 13.33, experienced masturbation by 14.5, first ejaculated by the age of 14.83, and had intercourse at age of 19.15 years. The first experienced ejaculation fell 1.5 years after the onset of puberty in 80% present of the cohort, and 84% starts masturbation 1.5 years after the onset of puberty. The mean response between the younger and the older subject was not statistical significance. CONCLUSIONS: It is appropriate to consider a request for semen specimens by masturbation from teenagers at one year and six months after the onset of puberty; the onset age of puberty plus 1.5 years is an important predictor of ejaculation and sample collection for cryopreservation. PMID- 26813356 TI - The Combination of DNA Ploidy Status and PTEN/6q15 Deletions Provides Strong and Independent Prognostic Information in Prostate Cancer. AB - PURPOSE: Aberrant DNA content has been discussed as a potential prognostic feature in prostate cancer. EXPERIMENTAL DESIGN: We analyzed the clinical significance of DNA ploidy in combination with prognostic relevant deletions of PTEN and 6q15 in 3,845 prostate cancers. RESULT: The DNA status was diploid in 67.8%, tetraploid in 25.6%, and aneuploid in 6.8% of tumors, and deletions of PTEN and 6q15 occurred in 17.8% and 20.3% of tumors. Abnormal DNA content and deletions were linked to high Gleason score, advanced tumor stage, and positive nodal stage (P < 0.0001 each). The risk of PSA recurrence increased from diploid to tetraploid and from tetraploid to aneuploid DNA status (P < 0.0001 each). However, 40% of patients with Gleason score >=4+4 and 55% of patients with PSA recurrence had diploid cancers. This fraction decreased to 21% (Gleason >=4+4) and 29% (PSA recurrence) if PTEN and/or 6q deletion data were added to ploidy data to identify cancers with an aberrant DNA status. The significance of combining both deletions and ploidy was further demonstrated in a combined recurrence analysis. Presence of deletions increased the risk of PSA recurrence in diploid (P < 0.0001), tetraploid (P < 0.0001), and aneuploid cancers (P = 0.0049), and the combination of ploidy data and deletions provided clinically relevant information beyond the CAPRA-S nomogram. Multivariate modeling including preoperatively and postoperatively available parameters identified the "combined DNA status" as a strong independent predictor of poor patient outcome. CONCLUSIONS: The combinatorial DNA content analysis involving general (ploidy) and specific events (deletions) has the potential for clinical utility in prostate cancer. Clin Cancer Res; 22(11); 2802-11. (c)2016 AACR. PMID- 26813357 TI - Vaccination against Oncoproteins of HPV16 for Noninvasive Vulvar/Vaginal Lesions: Lesion Clearance Is Related to the Strength of the T-Cell Response. AB - PURPOSE: Therapeutic vaccination with human papillomavirus type 16 (HPV16) E6 and E7 synthetic long peptides (SLP) is effective against HPV16-induced high-grade vulvar and vaginal intraepithelial neoplasia (VIN/VaIN). However, clinical nonresponders displayed weak CD8(+) T-cell reactivity. Here, we studied if imiquimod applied at the vaccine site could improve CD8(+) T-cell reactivity, clinical efficacy, and safety of HPV16-SLP (ISA101). EXPERIMENTAL DESIGN: A multicenter open-label, randomized controlled trial was conducted in patients with HPV16(+) high-grade VIN/VaIN. Patients received ISA101 vaccination with or without application of 5% imiquimod at the vaccine site. The primary objective was the induction of a directly ex vivo detectable HPV16-specific CD8(+) T-cell response. The secondary objectives were clinical responses (lesion size, histology, and virology) and their relation with the strength of vaccination induced immune responses. RESULTS: Forty-three patients were assigned to either ISA101 with imiquimod (n = 21) or ISA101 only (n = 22). Imiquimod did not improve the outcomes of vaccination. However, vaccine-induced clinical responses were observed in 18 of 34 (53%; 95% CI, 35.1-70.2) patients at 3 months and in 15 of 29 (52%; 95% CI, 32.5-70.6) patients, 8 of whom displayed a complete histologic response, at 12 months after the last vaccination. All patients displayed vaccine induced T-cell responses, which were significantly stronger in patients with complete responses. Importantly, viral clearance occurred in all but one of the patients with complete histologic clearance. CONCLUSIONS: This new study confirms that clinical efficacy of ISA101 vaccination is related to the strength of vaccine-induced HPV16-specific T-cell immunity and is an effective therapy for HPV16-induced high-grade VIN/VaIN. Clin Cancer Res; 22(10); 2342-50. (c)2016 AACRSee related commentary by Karaki et al., p. 2317. PMID- 26813358 TI - Expression and Role of the ErbB3-Binding Protein 1 in Acute Myelogenous Leukemic Cells. AB - PURPOSE: The ErbB3-binding protein 1 (Ebp1) has been implicated in diverse cancers as having either oncogenic or tumor suppressor activities. The present study was undertaken to determine the effects of Ebp1 expression in AML cells and to determine the mechanisms by which Ebp1 promotes cell proliferation in these cells. EXPERIMENTAL DESIGN: The expression of Ebp1 was studied in mononuclear cells obtained from the peripheral blood of 54 patients with AML by Western blot analysis. The effects of Ebp1 expression on proliferating cell nuclear antigen (PCNA) expression and cell proliferation was measured using Western blot analysis, immunoprecipitation, in vitro ubiquitination, and colony-forming assays. The role of Ebp1 in promoting rRNA synthesis and cell proliferation was evaluated by measuring the level of pre-rRNA and the recruitment of Pol I to rDNA. RESULTS: Ebp1 is highly expressed in acute myelogenous leukemia (AML) cells and regulates the level of ribosomal RNA (rRNA) synthesis by binding to RNA Polymerase I (Pol I) and enhancing the formation of the Pol I initiation complex. Ebp1 also increases the stability of PCNA protein by preventing its interaction with Mdm2, for which it is a substrate. CONCLUSIONS: These results demonstrate an important role of Ebp1 in promoting cell proliferation in AML cells through the regulation of both rRNA synthesis and PCNA expression. Clin Cancer Res; 22(13); 3320-7. (c)2016 AACR. PMID- 26813359 TI - Phase Ib Study of PEGylated Recombinant Human Hyaluronidase and Gemcitabine in Patients with Advanced Pancreatic Cancer. AB - PURPOSE: This phase Ib study evaluated the safety and tolerability of PEGylated human recombinant hyaluronidase (PEGPH20) in combination with gemcitabine (Gem), and established a phase II dose for patients with untreated stage IV metastatic pancreatic ductal adenocarcinoma (PDA). Objective response rate and treatment efficacy using biomarker and imaging measurements were also evaluated. EXPERIMENTAL DESIGN: Patients received escalating intravenous doses of PEGPH20 in combination with Gem using a standard 3+3 dose-escalation design. In cycle 1 (8 weeks), PEGPH20 was administrated twice weekly for 4 weeks, then once weekly for 3 weeks; Gem was administrated once weekly for 7 weeks, followed by 1 week off treatment. In each subsequent 4-week cycle, PEGPH20 and Gem were administered once weekly for 3 weeks, followed by 1 week off. Dexamethasone (8 mg) was given pre- and post-PEGPH20 administration. Several safety parameters were evaluated. RESULTS: Twenty-eight patients were enrolled and received PEGPH20 at 1.0 (n = 4), 1.6 (n = 4), or 3.0 MUg/kg (n = 20), respectively. The most common PEGPH20 related adverse events were musculoskeletal and extremity pain, peripheral edema, and fatigue. The incidence of thromboembolic events was 29%. Median progression free survival (PFS) and overall survival (OS) rates were 5.0 and 6.6 months, respectively. In 17 patients evaluated for pretreatment tissue hyaluronan (HA) levels, median PFS and OS rates were 7.2 and 13.0 months for "high"-HA patients (n = 6), and 3.5 and 5.7 months for "low"-HA patients (n = 11), respectively. CONCLUSIONS: PEGPH20 in combination with Gem was well tolerated and may have therapeutic benefit in patients with advanced PDA, especially in those with high HA tumors. Clin Cancer Res; 22(12); 2848-54. (c)2016 AACR. PMID- 26813360 TI - Comprehensive Transcriptome Profiling Reveals Multigene Signatures in Triple Negative Breast Cancer. AB - PURPOSE: By integrating expression profiles of mRNAs and long noncoding RNAs (lncRNA), we tried to develop and validate novel multigene signatures to facilitate individualized treatment of triple-negative breast cancer (TNBC) patients. EXPERIMENTAL DESIGN: We analyzed 165 TNBC samples and 33 paired normal breast tissues using transcriptome microarrays. Tumor-specific mRNAs and lncRNAs were identified and correlated with patients' recurrence-free survival (RFS). Using Cox regression model, we built two multigene signatures incorporating mRNAs and lncRNAs. The prognostic and predictive accuracy of the signatures were tested in a training set of 165 TNBC patients and validated in other 101 TNBC patients. RESULTS: We successfully developed an mRNA and an integrated mRNA-lncRNA signature based on eight mRNAs and two lncRNAs. In the training set, patients in the high-risk group were more likely to suffer from recurrent disease than patients in the low-risk group in both signatures [HR, 10.00; 95% confidence interval (CI), 2.53-39.47, P= 0.001; HR = 4.46, 95% CI, 1.34-14.91, P= 0.015 for integrated signature and mRNA signature, respectively). Results were validated in the validation set (P= 0.019 and 0.030, respectively). In addition, time dependent receiver operating curve showed that the integrated mRNA-lncRNA signature had a better prognostic value than both the eight-mRNA-only signature and the clinicopathologic risk factors in both sets. We also found through interaction analysis that patients classified into the low-risk group by the integrated mRNA-lncRNA signature had a more favorable response to adjuvant taxane chemotherapy. CONCLUSIONS: The multigene signature we developed can accurately predict clinical outcome and benefit of taxane chemotherapy in TNBC patients. PMID- 26813361 TI - Natural motion trajectory enhances the coding of speed in primate extrastriate cortex. AB - The ability to estimate the speed of an object irrespective of size or texture is a crucial function of the visual system. However, previous studies have suggested that the neuronal coding of speed in the middle temporal area (MT, a key cortical area for motion analysis in primates) is ambiguous, with most neurons changing their speed tuning depending on the spatial frequency (SF) of a visual pattern. Here we demonstrate that the ability of MT neurons to encode speed is markedly improved when stimuli follow a trajectory across the visual field, prior to entering their receptive fields. We also show that this effect is much less marked in the primary visual area. These results indicate that MT neurons build up on computations performed at earlier levels of the visual system to provide accurate coding of speed in natural situations, and provide additional evidence that nonlinear pooling underlie motion processing. PMID- 26813362 TI - Two Japanese siblings affected with Chikungunya fever with different clinical courses: Imported infections from the Cook Islands. AB - Two Japanese siblings visited the Cook Islands on business and stayed for 2 months. The sister developed a high fever, arthralgia, erythema and leg edema on the day after returning to Japan. The brother also developed neck and joint pain on the day following the sister's onset. Subsequently, his erythematous lesions spread over his whole body. Chikungunya virus was detected from the sister's blood and urine by specific reverse transcription polymerase chain reaction, but not in the brother's samples. Retrospectively, his history of Chikungunya fever was confirmed by the presence of the anti-Chikungunya virus immunoglobulin (Ig)M and IgG antibodies using the specific enzyme-linked immunoassay. In Japan, no autochthonous case of Chikungunya fever was reported previously. We should give attention to the imported infectious diseases for epidemic prevention. This report warns about the danger of the imported infectious diseases, and also suggests that covering the topic of infectious disease in the world is critical to doctors as well as travelers. PMID- 26813363 TI - [Strengthen the management on comorbidities of type 2 diabetes]. PMID- 26813364 TI - [Associations of sleep disorders with occurrence of diabetes and control of metabolic abnormalities]. PMID- 26813365 TI - [The pathogenesis and management of non-alcoholic fatty liver disease coexisted with type 2 diabetes]. PMID- 26813366 TI - [Effect of metformin on ventricular remodeling in patients with primary hypertension and type 2 diabetes mellitus]. AB - OBJECTIVE: To explore the effects of metformin on left ventricular remodeling in patients with primary hypertension and type 2 diabetes mellitus, and to investigate the effects of hypertension duration and duration of drug administration on metformin's cardiac action. METHODS: The clinical and echocardiographic data of 176 patients with primary hypertension and type 2 diabetes mellitus who were admitted to department of cardiology from January to December 2012 were retrospectively analyzed. The follow-up period was 6 to 24 months (the median follow-up time was 11 months). The patients were classified into two groups according to the usage of metformin: metformin group (n=84) and control group (n=92). The clinical data and echocardiography findings were evaluated both at baseline and follow-up. Subgroup analyses were used to assess the effects of hypertension duration and duration of drug medication on metfomin's action. RESULTS: At baseline, there was no significant difference in interventricular septum depth (IVSD), left ventricular posterior wall depth (LVPWD), and left ventricular mass index (LVMI) between the two groups. At the follow-up period, IVSD (P=0.001), LVPWD (P=0.04) and LVMI (P=0.01) were lower in metformin group. Multiple linear regression indicated that metformin had significant influence on LVPWD (P=0.02) and LVMI (P=0.04). At the follow-up period, LVMI was lower in two metformin subgroups. Additionally, LVMI was lower in the group which the patients took metformin for more than one year than that in control group (P=0.04). For patients whose hypertension duration was not shorter than 5 years, IVSD (P=0.01) and LVMI (P=0.02) were lower in metformin group at the follow-up period, compared with control group. CONCLUSIONS: Metformin may attenuate hypertrophy of left ventricular in patients with primary hypertension and type 2 diabetes mellitus. In patients with longer hypertension duration and longer duration of metformin use, metformin may show more obvious effects. PMID- 26813367 TI - [Clinical features of non-alcoholic fatty liver disease and its relationship with serum C-peptide levels in patients with latent autoimmune diabetes in adults]. AB - OBJECTIVE: To investigate the clinical features of non-alcoholic fatty liver disease (NAFLD) and its relationship with serum C-peptide levels in patients with latent autoimmune diabetes in adults (LADA). METHODS: A total of 155 patients with LADA who had no drinking history and were hospitalized in department of endocrinology and metabolism from January 2007 to June 2009 were divided into two groups, including patients with LADA but without NAFLD and patients with both LADA and NAFLD, according to Chinese medical association's guidelines of NAFLD and hepatic ultrasound result. Their clinical data and results of laboratory examinations were collected and analyzed, including medications, blood pressure, weight, height, waist circumference, hip circumference, fasting plasma glucose, 2 h postprandial plasma glucose, fasting C-peptide, 2 h postprandial C-peptide, hemoglobin A1c, renal function, liver function, blood lipid and C-reactive protein. The clinical features between two groups were compared and the relationship between serum C-peptide and NAFLD were also analyzed. RESULTS: Compared to the patients with LADA but without NAFLD, patients with both LADA and NAFLD had higher alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (gamma-GT) (all P<0.01), but the serum total bilirubin (TBI) and direct bilirubin (DBI) level had no significant inter-group difference (P>0.05). The patients with both LADA and NAFLD had higher fasting C peptide [0.62(0.33-0.93) vs 0.17 (0.05-0.50) nmol/L, P<0.001], 2 h postprandial C peptide [1.57(0.78-1.88) vs 0.42(0.06-1.01) nmol/L, P<0.001] and more severe insulin resistance [0.8(1.0-2.5) vs 0.6(0.2-1.3), P<0.001]. Logistic regression analysis showed that there was a significant association between fasting C peptide and the presence of NAFLD after controlling other confounding factors in patients with LADA. CONCLUSIONS: The patients with both LADA and NAFLD had more severe metabolic disorders and insulin resistance. Serum fasting C peptide was independently associated with the presence of NAFLD in patients with LADA. PMID- 26813368 TI - [Effect of CPAP therapy on dynamic glucose level in OSAHS patients with newly diagnosed T2DM]. AB - OBJECTIVE: To investigate the characteristic of dynamic glucose level in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients with newly diagnosed type 2 diabetes mellitus (T2DM) and to evaluate the effect of continuous positive airway pressure (CPAP) treatment on the glucose level. METHODS: A total of 65 cases of patients with T2DM who were newly diagnosed by oral glucose tolerance test (OGTT) were enrolled from April 2014 to April 2015 in Gansu Provincial Hospital, and divided into simple T2DM group (n=30) and OSAHS with T2DM group (n=35) according to aponea-hypopnea index (AHI) which was monitored by polysomnography (PSG). Their general clinical data were collected, and glucose level of different periods was monitored by continuous glucose moitoring system (CGMS). Changes of glucose level were compared between two groups before and after CPAP treatment. RESULTS: Age, gender proportion, BMI, smoking and drinking history, glycosylated hemoglobin (HbA1c) and blood lipid profile had no significantly difference between two groups. Longer neck circumstance and higher waist-hip ration (WHR), higher systolic blood pressure and diastolic blood pressure, higher fasting plasma glucose (FPG) [(9.4 +/- 3.2) vs (7.3 +/- 2.1) mmol/L, P=0.028] and fasting insulin (FINS) [(19.2 +/- 8.7) vs (11.1 +/- 4.7) mU/L, P=0.044] level, more serious homeostasis model assessment insulin resistance (HOMA-IR) were found in OSAHS patients with T2DM when compared to patients in simple T2DM group. The average dynamic glucose level of 24 hours, daytime, nocturnal and sleep time in OSAHS with T2DM group were higher than that in the simple T2DM group (all P<0.05). The alarming times when the average dynamic glucose level of nocturnal time was more than 0.1 mmol.L-1.min-1 in T2DM with OSAHS was more than that in control group (P=0.001). After treatment of CPAP, the level of AHI [(5.9 +/- 3.6) vs (56.7 +/- 11.4) times/h, P<0.001], average dynamic glucose level of 24 hours, day, nocturnal and sleep time were obviously decreased (all P<0.05); lowest saturation oxygen (LSpO2) was significantly increased [(92.3 +/- 3.7)% vs (81.5 +/- 20.2)%, P<0.001]; the alarming times and HOMA-IR were obviously decreased (P=0.019, 0.043). According to multiple linear regression analysis, the AHI (beta=0.736, P<0.001) in OSAHS with T2DM group was positively related to the average dynamic glucose level during sleep time, but the LSpO2(beta=-0.889, P<0.001) was negatively correlated. CONCLUSIONS: OSAHS patients with newly diagnosed T2DM have higher glucose level than that in simple T2DM patients, and CPAP therapy can obviously decrease the glucose level in newly diagnosed T2DM patients with OSAHS. AHI and LSpO2may influence the average dynamic glucose level during sleep time. PMID- 26813369 TI - [Effectiveness analysis of carotid endarterectomy in diabetic patients suffering from carotid stenosis]. AB - OBJECTIVE: To evaluate the perioperative complications and effectiveness of carotid endarterectomy (CEA) with diabetes mellitus (DM). METHODS: A total of 148 patients with carotid stenosis undergone CEA from December 2010 to December 2013 were collected and analyzed retrospectively. The patients were distributed into DM group (n=83) and the control group (n=65) according to the comorbidities. Age, gender, risk factors, stenosis degree, cerebral ischemic symptom, shunt in operation, perioperative complications and restenosis after one year in the two groups were analyzed and compared. RESULTS: There were no statistical difference between the two groups in terms of the general characteristic, clinical ischemic symptoms, concomitant disease, operative time, the amount of bleeding, the ratio of shunt (P>0.05). The rates of perioperative complications observed in DM group, including postoperative infection, neck hematoma, cranial nerves injured, acute cardiac infarction, stroke, hyperperfusion syndrome, all-cause mortality and one year restenosis after operation were 7.2%, 12.0%, 10.8%, 3.6%, 6.0%, 9.6%, 2.4% and 9.6% respectively. The complication rates observed in the control group, on the other hand were 3.1%, 9.2%, 4.6%, 1.5%, 4.6%, 7.7%, 1.5% and 3.1% respectively. There were no significant statistical difference between the two groups (chi2 =0.551, 0.300, 1.898, 0.069, 0, 0.172, 0.138, 1.559, P>0.05). CONCLUSION: CEA may be safe and effective in diabetic patients suffering from carotid stenosis, on the condition that the blood glucoses of the patients are controlled well, and the cardio cerebral vascular system is carefully assessed and intervened before the operation. PMID- 26813370 TI - [Analysis of clinical relevant bleeding events in the elderly patients with acute pulmonary thromboembolism after treatment]. AB - OBJECTIVE: To investigate the incidences of clinical relevant bleeding events and risk factors in elderly patients with acute pulmonary thromboembolism (PTE). METHODS: Between January of 2009 and December of 2013, a total of 539 initially diagnosed PTE patients were recruited in our study in Beijing Chao Yang hospital. Basic clinical characteristics, medical history, imaging results, laboratory tests, therapy and outcomes (including mortality, recurrence and incidences of bleeding events) were collected during 3 months' follow-up. All the patients were divided into two groups according to age (<= 65 years and >65 years ), and these parameters were compared between the two groups. RESULTS: Compared with younger patients (<= 65 years old), older patients (>65 years) had higher incidences of total bleeding, clinical relevant non-major bleeding (20.2% vs 13.4%, P=0.038; 16.7% vs 10.5%, P=0.043). The incidence of gastrointestinal bleeding of the elderly was also higher than that of younger patients (6.0% vs 1.4%, P=0.005) and majority of bleeding events were within 1 month after initial treatment. For the elderly, chronic liver diseases (P=0.001, OR=9.229), ischemic stroke (P=0.001, OR=6.323) and anemia (P=0.014, OR=3.774) were independent risk factors for major bleeding, and malignancy (P<0.001, OR=3.140) was independent risk factor for clinical relevant non-major bleeding. The independent risk factors for gastrointestinal bleeding were diabetes mellitus (P=0.012, OR=3.711) and anemia (P<0.001, OR=5.863). CONCLUSIONS: The older PTE patients had higher incidences of total bleeding and clinical relevant non-major bleeding. Gastrointestinal bleeding of the elderly was also higher than that of younger patients and mainly occurred within 1 month after initial treatment. Complications can increase the risk of bleeding in older PTE patients. PMID- 26813371 TI - [Curative effect analysis of rituximab combined with intensive chemotherapy for follicular lymphoma patients with bone marrow involvement]. AB - OBJECTIVE: To investigate the efficacy of different regimens in previously untreated follicular lymphoma (FL) patients with bone marrow involvement. METHODS: Clinical data of 38 previously untreated FL patients with bone marrow involvement visited Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences during the period from January 2002 to December 2013 were analyzed retrospectively, in order to compare the efficacy and survival status of different regimens. RESULTS: The median age of onset was 43 years (19 74 years). The number of patients in low, intermediate and high risk group according to the follicular lymphoma international prognostic index (FLIPI) was 11 (28.9%), 11 (28.9%), and 16 (42.1%) respectively.And 36 of the 38 patients received combined chemotherapies. The overall response rate (ORR), complete remission (CR) rate, and partial remission (PR) rate were 100%, 66.7%, and 33.3%, respectively.A total of 31 patients (86.1%) used rituximab, in whom the 3-year overall survival (OS) was significantly higher than that in those who had not used rituximab (94.4% vs 80.0%, P=0.012), but the difference between 3-year progression-free survival (PFS) rate had no statistical significance (P=0.305). In the rituximab group, 16 patients had received RCHOP (rituximab, cyclophosphamide, epirubicin, vincristine, prednisone), 9 patients had received RFC (rituximab, fludarabine, cyclophosphamide), 6 young patients with high invasion and high tumor burden had received R-HyperCVAD (rituximab , cyclophosphamide, epirubicin, vincristine, dexamethasone). In the RFC/R-HyperCVAD group, the 3-year PFS was significantly higher than that in the RCHOP group (92.3% vs 48.9%, P=0.036), but the 3-year OS rate had no statistically significant difference (P=0.190). Compared with the RCHOP group, the 3-year PFS was significantly higher in the RFC group (100% vs 48.9%, P=0.029), but the 3 year OS rate had no statistically significant difference (100% vs 85.7%, P=0.285). Of the 36 patients who had received combined chemotherapy, 13 had received rituximab for maintenance treatment, whose 3-year PFS (92.3% vs 58.7%, P=0.025) and OS (100% vs 80.0%, P=0.040) were significantly higher than those not receiving maintenance treatment. CONCLUSIONS: FL patients with bone marrow involvement may tend to have an onset at young age and intermediate to high FLIPI scores. These patients may benefit from rituximab combined with intensive chemotherapy. Rituximab as maintenance treatment may further improve the survival of these patients. PMID- 26813373 TI - [Prognostic value of extra-vascular lung water index and pulmonary vascular permeability index in patients with ARDS]. AB - OBJECTIVE: To investigate the correlation of the extra-vascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) with disease severity and their prognostic value in patients with acute respiratory distress syndrome (ARDS). METHODS: A total of 44 patients with ARDS from October 2012 to June 2014 admitted in the Second Affiliated Hospital of Wenzhou Medical University were recruited in this study. According to the severity, patients were divided into three groups (Mild group, Moderate group and Severe group); the acute physiology and chronic health evaluation system II score (APACHE II), the lung injury score (LIS), the pulse contour curve continuous cardiac output (PiCCO) and other clinical indicators were respectively monitored in the period of 24, 48, 72 hrs after admission; then the correlation of EVLWI, PVPI and oxygenation index (OI) among groups were analyzed; According to the prognosis, patients were divided into the survival group and the death group, both given the univariate and multivariate Logistic regression analysis; EVLWI, PVPI, APACHE II score, LIS and lactic acid were admitted into the receiver operating characteristic (ROC) curve analysis, and the prognosis was evaluated respectively. RESULTS: With the increase of disease severity, LIS and lactic acid gradually increased, the difference was significant among the three groups of Mild, Moderate and Severe (P<0.05). And the APACHE II score also increased gradually with the severity, but the difference was statistically significant only between the Mild group and the Severe group (P<0.01). And likewise, mild, moderate, severe ARDS patients had 1, 6, 9 cases of death, respectively. The 28 day mortality rate increased gradually after admission, with a significant difference between the Mild group and the Severe group (P<0.05). When all the 44 patients of three severities (during the 24 hrs period and during the 72 hrs period) were compared, the OI gradually decreased with the increase of severity of ARDS, while EVLWI and PVPI ascended, and differences between any two groups were statistically significant (P<0.05). In addition, there was a significant negative correlation between EVLWI and OI or between PVPI and OI (r=-0.666, 0.763, all P<0.01), and a significant positive correlation between EVLWI and PVPI, the APACHE II score or LIS (r=0.929, 0.895, 0.661, all P<0.01). Besides, OI was a predictive protection factor of ARDS, whereas lactic acid, EVLWI and PVPI were risk factors. Multivariate Logistic regression analysis showed that EVLWI and lactic acid were risk factors for ARDS death (all P<0.05). ROC curve analysis results suggested EVLWI and lactic acid were risk factors, (odd ratio (OR)> 1, and 95%CI: 1.071-5.201, 5.201-99.852, all P<0.05). CONCLUSION: EVLWI, PVPI were positively correlated with the severity of ARDS illness; EVLWI can be used as an independent risk factor for forecasting ARDS death, jointing EVLWI with PVPI could improve the accuracy of ARDS death forecasting. PMID- 26813372 TI - [Value of cardiopulmonary exercise testing in comparing cardio-pulmonary function among patients with three kinds of pulmonary artery hypertension]. AB - OBJECTIVE: To assess the exercise capacity of three kinds of pulmonary artery hypertension using cardiopulmonary exercise testing (CPET). METHODS: In the Center for Pulmonary Vascular Disease Diagnosis and Treatment of Fuwai Hospital, idiopathic pulmonary artery hypertension (IPAH), congenital heart disease associated pulmonary artery hypertension (CHD-PAH), connective tissue disease associated pulmonary artery hypertension (CTD-PAH) were enrolled into this study from December 2012 to May 2013. CPET was performed in all patients, and clinical features, routine tests results, N-terminal B-type natriuretic peptide (NT proBNP), Six-minutes-walk distance (6MWD) were all collected. RESULTS: Thirty-two patients with IPAH, 38 patients with CHD-PAH, 25 patients with CTD-PAH were enrolled. For IPAH, CHD-PAH, and CTD-PAH patients, the peak oxygen uptake via body weight (VO2max/kg) was (12.3 +/- 2.3), (14.9 +/- 4.0), and (11.1 +/- 2.5) ml.min-1.kg-1, respectively. The peak VO2/kg was significantly different within these three groups (P<0.001), and was significantly higher in CHD-PAH patients compared with the other two groups (P=0.003, P<0.001). The peak VO2/heart rate (HR) was (5.8+/-1.4), (6.4 +/- 1.8), (5.3 +/- 1.7) ml.beat(-1).min-1 in the above three groups and was significantly different within these three groups (P=0.034). The peak VO2/HR was significantly increased in CHD-PAH patients than CTD-PAD patients (P=0.012). The peak HR was (136.1 +/- 21.4), (140.8 +/- 19.9), (124.5 +/ 21.6) beat/min respectively and was significantly lower in CTD-PAD patients than CHD-PAH patients (P=0.009). The 6MWD was significantly decreased in CTD-PAD patients compared with CHD-PAH and IPAH patients (P=0.006, 0.010). Nt-proBNP was significantly decreased in CTD-PAD patients compared with CHD-PAH patients (P=0.012). In Pearson and partial correlation analysis, the peak VO2/kg was significantly correlated with peak VO2/HR, peak HR, 6MWD, Nt-proBNP, left ventricular end-diastolic diameter, right ventricular end-diastolic diameter (r=0.477, 0.518, 0.387, 0.465, -0.350, 0.349, -0.259). CONCLUSION: CPET parameters can objectively evaluate exercise capacity and cardiopulmonary function of the patients with pulmonary hypertension. PMID- 26813374 TI - [Application of plasmapheresis combined with hemofiltration in the treatment of severe liver disease in middle and late pregnancy]. AB - OBJECTIVE: To investigate the application and security of plasmapheresis combined with hemofiltration in the treatment of severe liver disease in middle and late pregnancy. METHODS: Clinical data of 29 patients of middle and late pregnancy with severe liver disease from March 2009 to November 2013 in the Third Affiliated Hospital of Sun Yat-sen University was analyzed retrospectively. According to the therapeutic schedule, patients were divided into control group (n=16, 18-29 years old, median age of 24 years old) and treatment group (n=13, 21 28 years old, median age of 25 years old). The informed consents of all patients were obtained and the ethical committee approval was received. The control group was given the treatment of resisting infection, protecting liver, reducing jaundice, supplying albumin and globulin, infusing blood coagulation and so on. The treatment group was given plasmapheresis and hemofiltration on the basis of the above-mentioned treatment. The differences of major clinical indicators such as MELD scores, APACHEII scores, total bilirubin (TB), albumin (ALB), prothrombin time activity (PTA) , fasting blood glucose (FPG), serum creatinine (Scr) of peripheral venous blood and arterial lactic acid (Lac) in patients of two groups were observed 6 hours before and 1, 3, 5 days after the treatment. The major clinical indicators in patients of two groups were compared by t test and the clinical efficient were compared by chi2 test. RESULTS: There were no statistical differences of the clinical indicators between the two groups 6 hours before the treatment (all P>0.05). The MELD scores, APACHEII scores, TB, ALB, PTA, FPG, Scr, Lac were (25 +/- 6) scores, (22 +/- 5) scores, (197 +/- 69) umol/L, (30 +/- 7) g/L, (55 +/- 24)%, (5.7 +/- 2.4) mmol/L, (111 +/- 42) umol/L, (2.3 +/- 0.6) mmol/L in treatment group 1 day after treatment, and were (33 +/- 8) scores, (30 +/- 7) scores, (299 +/- 113) umol/L, (24 +/- 6) g/L, (33 +/- 11)%, (3.7 +/- 1.7) mmol/L, (165 +/- 82) umol/L, (4.4 +/- 1.5) mmol/L in control group, which improved significantly in the treated group compared to those in the control group. There was also significant improvement in those posttreatment d3, and 5 lab findings in the treatment group (P<0.05). The effective rate was higher in the treatment group (92%, 12/13) than the control group (56%, 9/16) (chi2 =4.215, P<0.05). Kaplan-Meier analysis showed the combined treatment could significantly improve the 42 d survival rate in postpartum patients with liver function failure. One patient had transitional hypotension after plasma infusion and hemofiltration in the treatment group, but the blood pressure returned to normal 1 h after small dose of vasoconstrictor. CONCLUSION: The therapeutic effect of plasmapheresis combined with hemofiltration on the treatment of severe liver disease in middle and late pregnancy is safe and effective, and it could improve the clinical outcomes and survival rate. PMID- 26813375 TI - [Clinical and high-resolution computed tomography characteristics of the welder's pneumoconiosis]. AB - OBJECTIVE: To investigate the clinical and high-resolution computed tomography (HRCT) features of the welder's pneumoconiosis. METHODS: A total of 10 patients diagnosed by bronchoscopy and pathology from January 2010 to January 2015 in Nanjing Drum Tower Hospital were recruited in this study, and the clinical manifestations, pulmonary function tests, pathology and HRCT data were collected and analyzed retrospectively. RESULTS: Ten patients all had welder's occupational history for 5-30 years, with the main clinical manifestations of cough, sputum production, chest tightness and other symptoms. And the ratio of forced expiratory volume in one second and forced vital capacity (FEV1/FVC) of 4 patients was lower than 75.0% in the pulmonary function tests. Transbronchial lung biopsy specimen showed numerous hemosiderin-laden macrophages within the alveolar space, associated with positive iron staining. In welder's pneumoconiosis, small centrilobular nodules (10 cases) were frequently seen on HRCT in bilateral lung fields, with branching linear structures or the tree buds like shadows in 7 cases; 3 patients also showed areas of ground-glass attenuation. And the patients were misdiagnosed as tuberculosis (1/10), interstitial pneumonia (3/10), allergic alveolitis (1/10), diffuse lung disease (2/10), and vasculitis (1/10). CONCLUSIONS: Clinical manifestations of welder's pneumoconiosis are not specific; small centrilobular nodules are frequently seen on HRCT, with linear opacities or tree bud-like shadows. PMID- 26813376 TI - [Diagnostic value of serum procalcitonin in urinary tract infection]. AB - OBJECTIVE: To analyze the serum level of procalcitonin (PCT) in urinary tract infection (UTI) patients with urinary obstruction or bacteremia, and to investigate the value of PCT in diagnosing UTI. METHODS: A total of 102 patients with UTI hospitalized from January to December 2013 in the Second Hospital of Tianjin Medical University were categorized into obstructed UTI (n=60) and non obstructed UTI (n=42), whose serum PCT concentrations were compared. Blood cultures were implemented in 44 patients, including 13 with positive findings (bacteremia) and 31 with negative findings (non-bacteremia). Serum PCT levels were also compared between the bacteremia and non-bacteremia groups. Receiver operating characteristic (ROC) curves were constructed to illustrate the performance of PCT in diagnosing urinary obstruction and bacteremia. RESULTS: The median serum concentration of PCT in the obstructed UTI group (1.71 (0.10-53.20) mg/L)was higher than that in the non-obstructed UTI group (0.21 (0.10-10.00) mg/L, P<0.001); the serum concentration of PCT in the bacteremia group (2.73 (0.10-41.60) mg/L) was higher than that in the non-bacteremia group (0.42 (0.10 53.20) mg/L, P=0.030). The area under ROC curve of PCT in diagnosing urinary obstruction and bacteremia was 0.80 (95% CI 0.71-0.89) and 0.71 (95% CI 0.53 0.88). The maximum negative predictive value (NPV) was 0.90 and 0.87, respectively, when the serum concentrations of PCT diagnosing bacteremia and urinary obstruction was 0.51 mg/L and 0.35 mg/L. CONCLUSION: PCT may be of some value in diagnosing UTI with urinary obstruction or bacteremia. PMID- 26813377 TI - [Factors affecting residual stones after percutaneous nephrolithotomy in patients with renal calculus]. AB - OBJECTIVE: To explore the factors affecting the residual stones after percutaneous nephrolithotomy (PCNL) in patients with renal calculus. METHODS: A retrospective analysis was performed for 1 200 patients who were affected by renal calculus and treated with PCNL between Jan 2008 and May 2014 in People's Hospital of Anyang City. Among those patients, 16 were diagnosed as bilateral renal stone and had two successive operations. The size, location and number of stones, previous history of surgery, the degree of hydronephrosis, urinary infection were included in the univariate analysis. Significant factors in univariate analysis were included in the multivariate analysis to determine factors affecting stone residual. RESULTS: A total of 385 cases developed stone residual after surgery. The overall residual rate was 31.7%. In univariate analysis, renal pelvis combined with caliceal calculus (P=0.006), stone size larger than 4 cm (P=0.005), stone number more than 4 (P=0.002), the amount of bleeding more than 200 ml (P=0.025), operation time longer than 120 minutes (P=0.028) were associated with an increased rate of stone residual. When subjected to the Cox multivariate analysis, the independent risk factors for residual stones were renal pelvis combined with caliceal calculus (P=0.049), stone size larger than 4 cm (P=0.038) and stone number more than 4 (P=0.018). CONCLUSIONS: Factors affecting the incidence of residual stones after PCNL are the size, location and number of stones. Larger size stone and the presence of renal pelvis combined with caliceal calculus are significantly associated with residual stones. Nevertheless, stone number less than 4 indicates an increased stone clearance rate. PMID- 26813378 TI - [Expression of HCN4 protein in ventricular outflow tract of rabbit with idiopathic ventricular tachycardia]. AB - OBJECTIVE: To confirm the existence of purkinje fibers in rabbit outflow tract tissue and explore the role of Hyperpolarization-Activated Cyclic Nucleotide Gated Channel 4 (HCN4) protein in idiopathic ventricular tachycardia. METHODS: A total of ten New Zealand white rabbits were randomly selected to observe whether there were pukinje fibers in outflow tract by the methods of HE staining and immunohistochemical detection of midsize neurofilament (NF-M). Forty rabbits were randomly divided into four groups: normal control group (SO), ventricular tachycardia group (VT), ventricular tachycardia+ esmolol intervention group (VT+ ESM) and ventricular tachycardia+ ivabradine intervention group (VT+ IVA). Immunohistochemistry was used to detect the expression of HCN4 protein in ventricular outflow tract; the required output voltage amplitude was recorded when ventricular tachycardia was induced; the times and duration of spontaneous ventricular tachycardia when stimulation stopped were also recorded for each group. RESULTS: (1)Purkinje fibers existed in the myocardial tissue of rabbit outflow tract. (2)HCN4 protein expression significantly increased in VT group compared with SO group (left ventricular: 97.6 +/- 16.7 vs 29.0 +/- 8.0, P<0.01; right ventricular: 92.7 +/- 12.3 vs 26.0 +/- 10.8, P<0.01), the expression of HCN4 protein obviously reduced in VT+ IVA group compared with VT group (left ventricular: 32.0 +/- 9.4 vs 97.6 +/- 16.7, P<0.01; right ventricular: 30.8 +/- 12.4 vs 92.7 +/- 12.3, P<0.01). (3)The output voltage amplitude required to induce the desired ventricular tachycardia in VT+ ESM group and VT+ IVA group were higher than the VT group, under the same high frequency stimulation (P<0.01); the times and duration of spontaneous ventricular tachycardia in VT+ ESM group and VT+ IVA group significantly reduced when the stimulation stopped, compared with the VT group (both P<0.01). CONCLUSIONS: (1)Purkinje fibers exist in ventricular outflow tract, which may be the histological origin of the ventricular tachycardia. (2)HCN4 protein is up-regulated in ventricular outflow tract when ventricular tachycardia occurs. (3)Esmolol and ivabradine can prevent and reduce the occurrence of ventricular tachycardia, and as the specific inhibitor of the HCN channel, the effect of ivabradine is more obvious. PMID- 26813379 TI - [Meta-analysis of percutaneous transluminal atherectomy in the treatment for in stent restenosis of lower extremity peripheral artery disease]. AB - OBJECTIVE: To evaluate the clinical safety and efficacy of percutaneous transluminal atherectomy for in-stent restenosis (ISR) in patients with low extremity peripheral arterial diseases (PAD). METHODS: PubMed, Elsevier, EBSCO, Spring databases and Cochrane Library were searched for relevant articles. Based on the different mechanisms of atherectomy, the patients were divided into mechanic atherectomy group and laser atherectomy group. The safety end points included the rate of distal embolism and severe arterial wall injuries. And the efficacy end points included primary patency rate and freedom from target vessel revascularization (TVR-free) 6 months and 12 months after surgery. RESULTS: A total of 9 studies and 620 patients (published between 2006 and 2014) were accepted. The rate of distal embolism was 4.2% (95% confidence interval (CI): 1.7%-6.7%), while that of severe arterial wall injuries was 1.9% (95%CI: 0.9% 3.0%), respectively. Laser atherectomy was responsible for more distal embolism (6.8%) compared to mechanic atherectomy (2.0%), which was significantly different (Q=21.66, P=0.010). At 6-month follow-up, primary patency rate and rate of TVR free were 63.0% (95% CI: 55.5%-70.6%) and 80.4% (95% CI: 70.5%-90.3%), while at 12-month follow-up were 43.5% (95%CI: 32.2%-54.9%) and 58.0% (95% CI: 52.1% 63.9%), respectively. The free-TVR rate at 6 months follow-up in mechanical atherectomy group was 77.9%, and was inferior to that in laser atherectomy group (80.8%, Q=13.49, P=0.009). Published bias was discovered at the analysis of 12 month TVR-free rate by means of Begg Test (P=0.039). Meta analysis concerned about the 3 randomized controlled trials demonstrated that there was no significant improvement using atherectomy for ISR comparing to standard balloon at 6-month TVR-free rate (OR=1.34, 95% CI: 0.86-2.07, P=0.196). CONCLUSIONS: To treat ISR lesion in lower extremities, laser atherectomy has a lower free-TVR rate in the middle term follow-up.A higher rate of distal embolism is noted though. On balance, percutaneous transluminal atherectomy demonstrates no significant improvement compared to plain balloon angioplasty for ISR lesions. PMID- 26813380 TI - [Preliminary establishment of quantitative detection for luteinizing hormone based on superparamagnetic particles labeled immuno chromatography method]. AB - OBJECTIVE: To develop a quick quantitative detecting method for luteinizing hormone(LH) based on superparamagnetic particles labeled immunochromatography technology. METHODS: Magnetic particles were catalyzed by EDC/NHS, LH monoclonal antibody were coupled with magnetic particles, another antibody were coated with the NC membrane, established a quantitative detecting method combined sand wish assay format with immunochromatography. The performance of this method was evaluated by linear range, precision, accuracy, specificity and stability. Detecting the serum sample that were tested by chemiluminescence immunoassay (CLIA) which was high credibility to verify the reliability. RESULTS: The reaction time of LH antibody coupled magnetic particles, LH and LH antibody coated in nitrocellulose membrane was 20 min; the coefficient of variation (CV) values for low, median, high were 8%-12%, the bias was less than 10%, recovery rate was 90%-120%, the minimum detection limit was 0.63 mIU/ml, no obvious cross reaction with human chorionic gonadotropin (HCG), thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH). Test results of clinical sample had good correlation with CLIA (R2 =0.96, P<0.05). CONCLUSION: The superparamagnetic particles labeled immuno-chromatography method is simple and rapid, and is expected to become a direction in the development for point-of-care test (POCT) quantitative detection of micro components in biological sample. PMID- 26813381 TI - Contribution of writing to reading: Dissociation between cognitive and motor process in the left dorsal premotor cortex. AB - Functional brain imaging studies reported activation of the left dorsal premotor cortex (PMd), that is, a main area in the writing network, in reading tasks. However, it remains unclear whether this area is causally relevant for written stimulus recognition or its activation simply results from a passive coactivation of reading and writing networks. Here, we used chronometric paired-pulse transcranial magnetic stimulation (TMS) to address this issue by disrupting the activity of the PMd, the so-called Exner's area, while participants performed a lexical decision task. Both words and pseudowords were presented in printed and handwritten characters. The latter was assumed to be closely associated with motor representations of handwriting gestures. We found that TMS over the PMd in relatively early time-windows, i.e., between 60 and 160 ms after the stimulus onset, increased reaction times to pseudoword without affecting word recognition. Interestingly, this result pattern was found for both printed and handwritten characters, that is, regardless of whether the characters evoked motor representations of writing actions. Our result showed that under some circumstances the activation of the PMd does not simply result from passive association between reading and writing networks but has a functional role in the reading process. At least, at an early stage of written stimuli recognition, this role seems to depend on a common sublexical and serial process underlying writing and pseudoword reading rather than on an implicit evocation of writing actions during reading as typically assumed. PMID- 26813382 TI - Corrigendum: Disparate developmental patterns of immune responses to bacterial and viral infections in fish. PMID- 26813384 TI - Semiquantum key distribution with secure delegated quantum computation. AB - Semiquantum key distribution allows a quantum party to share a random key with a "classical" party who only can prepare and measure qubits in the computational basis or reorder some qubits when he has access to a quantum channel. In this work, we present a protocol where a secret key can be established between a quantum user and an almost classical user who only needs the quantum ability to access quantum channels, by securely delegating quantum computation to a quantum server. We show the proposed protocol is robust even when the delegated quantum server is a powerful adversary, and is experimentally feasible with current technology. As one party of our protocol is the most quantum-resource efficient, it can be more practical and significantly widen the applicability scope of quantum key distribution. PMID- 26813383 TI - Comparison of the effect of recombinant bovine wild and mutant lipopolysaccharide binding protein in lipopolysaccharide-challenged bovine mammary epithelial cells. AB - Lipopolysaccharide (LPS)-binding protein (LBP) plays a crucial role in the recognition of bacterial components, such as LPS that causes an immune response. The aim of this study was to compare the different effects of recombinant bovine wild LBP and mutant LBP (67 Ala -> Thr) on the LPS-induced inflammatory response of bovine mammary epithelial cells (BMECs). When BMECs were treated with various concentrations of recombinant bovine lipopolysaccharide-binding protein (RBLBP) (1, 5, 10, and 15 MUg/mL) for 12 h, RBLBP of 5 MUg/mL increased the apoptosis of BMECs induced by LPS without cytotoxicity, and mutant LBP resulted in a higher cell apoptosis than wild LBP did. By gene-chip microarray and bioinformatics, the data identified 2306 differentially expressed genes that were changed significantly between the LPS-induced inflamed BMECs treated with 5 MUg/mL of mutant LBP and the BMECs only treated with 10 MUg/mL of LPS (fold change >=2). Meanwhile, 1585 genes were differently expressed between the inflamed BMECs treated with 5 MUg/mL of wild LBP and 10 MUg/mL of LPS-treated BMECs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that these differentially expressed genes were involved in different pathways that regulate the inflammation response. It predicted that carriers of this mutation increase the risk for a more severe inflammatory response. Our study provides an overview of the gene expression profile between wild LBP and mutant LBP on the LPS-induced inflammatory response of BMECs, which will lead to further understanding of the potential effects of LBP mutations on bovine mammary glands. PMID- 26813385 TI - From the Editors. PMID- 26813386 TI - Perinatal Nurses: Key to Increasing African American Breast-Feeding Rates. PMID- 26813387 TI - Pharmacologic Treatment of Patent Ductus Arteriosus in the Preterm Infant. PMID- 26813388 TI - Common Questions on Documentation. PMID- 26813389 TI - Internet Resources. PMID- 26813390 TI - Shedding Light on Inherited Thrombophilias: The Impact on Pregnancy. AB - Physiologic changes of pregnancy result in a hypercoagulable state, placing the risk for venous thromboembolic events at 1 in 1600 births. Venous thromboembolic events are one of the leading causes of maternal mortality. A correlation among venous thromboembolic events, pregnancy complications, and inherited thrombophilia continues to be investigated. This article primarily focuses on the impact of inherited thrombophilias on pregnancy, labor, and birth and yet also addresses acquired thrombophilia. Prophylactic and therapeutic perinatal anticoagulation are lifesaving and pregnancy-sparing interventions. Interprofessional management of these high-risk pregnancies allows for increased surveillance to reduce perinatal morbidity and mortality. PMID- 26813392 TI - Intrauterine Tobacco Smoke Exposure and Congenital Heart Defects. AB - Tobacco use and second-hand smoke exposure during pregnancy are linked to a host of deleterious effects on the pregnancy, fetus, and infant. Health outcomes improve when women quit smoking at any time during the pregnancy. However, the developing heart is vulnerable to noxious stimuli in the early weeks of fetal development, a time when many women are not aware of being pregnant. Congenital heart defects are the most common birth defects. Research shows an association between maternal tobacco exposure, both active and passive, and congenital heart defects. This article presents recent evidence supporting the association between intrauterine cigarette smoke exposure in the periconceptional period and congenital heart defects and discusses clinical implications for practice for perinatal and neonatal nurses. PMID- 26813391 TI - Pulmonary Disorders Complicating Pregnancy: An Overview. AB - Awareness of pulmonary complications and the timely execution of appropriate interventions are critical to maintaining adequate oxygenation for the pregnant woman and the fetus. Clinicians have an opportunity during prenatal visits to provide women with education regarding pulmonary complications during pregnancy to promote positive maternal and fetal outcomes. The pulmonary conditions to be addressed in this article include asthma, tuberculosis, cystic fibrosis, and pneumonia. The purpose of this manuscript is to provide an overview of specific pulmonary conditions, as well as interventions related to each disorder and its impact on pregnancy. PMID- 26813393 TI - Care of the Family of an Infant With a Congenital Heart Defect During the NICU Hospitalization. AB - The family of an infant born with a congenital heart defect is challenged by both the short- and long-term implications of the diagnosis and the neonatal intensive care unit (NICU) hospitalization. Nurses are in a key position to support these families as they deal with the psychological, emotional, and financial impact of the NICU experience. Understanding how families perceive the NICU environment and their grief in losing the desired healthy baby provides the NICU nurse with the knowledge to engage in self-reflection on her or his interpersonal style and caregiving attitudes. Utilizing the concepts and principles of family-centered care and relationship-based practice, nurses can work together with the families to determine how to best meet the families' needs and to find the resources to support them. Families and colleagues appreciate nurses who demonstrate expertise in this approach to family-centered care. This appreciation leads to greater job satisfaction and decreased job-related stress. PMID- 26813394 TI - Cardiovascular Transition of the Extremely Premature Infant and Challenges to Maintain Hemodynamic Stability. AB - The intricate fetal circulatory blood flow undergoes abrupt changes and restructuring at birth, allowing transition to extrauterine life and survival. In the extremely low-birth-weight newborn infant (birth weight <1000 g), these changes are affected by the immaturity of the fetal cardiovascular and pulmonary systems. The immature physiology associated with the inability to transition properly can lead to a poor prognosis and create problematic issues for the clinical management of these infants. Potentially problematic issues and complications include immature myocardium, adrenal insufficiency, patent ductus arteriosus, hypotension, and anemia. Understanding the unique transition to extrauterine life for these infants, problems that arise from immaturity and incomplete transition, and current approaches to management will help nurses and physicians caring for ELBW infants to improve the care they give and minimize mortality and morbidity in this vulnerable population. This article will review transitional physiology for term and preterm newborns, potential problems and complications, and current management approaches. PMID- 26813395 TI - Complications of Long-Term Prostaglandin E1 Use in Newborns With Ductal-Dependent Critical Congenital Heart Disease. AB - Prostaglandin E1 (PGE1) has been used for decades in the medical treatment of ductal dependent critical congenital heart disease in neonates. The article is a report of a retrospective evaluation of the long-term effects of PGE1 in a neonatal intensive care unit in Saudi Arabia. There were 22 subjects with a wide spectrum of cardiac defects maintained on PGE1 for a mean of 38 days (range: 6 200 days). The majority of the complications included hypokalemia, hypotension, and apnea/bradycardia. Pseudo-Barett syndrome and gastric outlet obstruction were also found. While long-term administration of PGE1 is rare in North America, it is important to be aware of possible adverse effects of fluid and electrolyte imbalance, gastric outlet obstruction, and feeding difficulties. PMID- 26813396 TI - Human Papillomavirus Vaccinations. PMID- 26813399 TI - Strategies for regeneration of components of nervous system: scaffolds, cells and biomolecules. AB - Nerve diseases including acute injury such as peripheral nerve injury (PNI), spinal cord injury (SCI) and traumatic brain injury (TBI), and chronic disease like neurodegeneration disease can cause various function disorders of nervous system, such as those relating to memory and voluntary movement. These nerve diseases produce great burden for individual families and the society, for which a lot of efforts have been made. Axonal pathways represent a unidirectional and aligned architecture allowing systematic axonal development within the tissue. Following a traumatic injury, the intricate architecture suffers disruption leading to inhibition of growth and loss of guidance. Due to limited capacity of the body to regenerate axonal pathways, it is desirable to have biomimetic approach that has the capacity to graft a bridge across the lesion while providing optimal mechanical and biochemical cues for tissue regeneration. And for central nervous system injury, one more extra precondition is compulsory: creating a less inhibitory surrounding for axonal growth. Electrospinning is a cost-effective and straightforward technique to fabricate extracellular matrix (ECM)-like nanofibrous structures, with various fibrous forms such as random fibers, aligned fibers, 3D fibrous scaffold and core-shell fibers from a variety of polymers. The diversity and versatility of electrospinning technique, together with functionalizing cues such as neurotrophins, ECM-based proteins and conductive polymers, have gained considerable success for the nerve tissue applications. We are convinced that in the future the stem cell therapy with the support of functionalized electrospun nerve scaffolds could be a promising therapy to cure nerve diseases. PMID- 26813400 TI - Optimal sequence of tests for the mediastinal staging of non-small cell lung cancer. AB - BACKGROUND: Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer and the most difficult to predict. When there are no distant metastases, the optimal therapy depends mainly on whether there are malignant lymph nodes in the mediastinum. Given the vigorous debate among specialists about which tests should be used, our goal was to determine the optimal sequence of tests for each patient. METHODS: We have built an influence diagram (ID) that represents the possible tests, their costs, and their outcomes. This model is equivalent to a decision tree containing millions of branches. In the first evaluation, we only took into account the clinical outcomes (effectiveness). In the second, we used a willingness-to-pay of ? 30,000 per quality adjusted life year (QALY) to convert economic costs into effectiveness. We assigned a second-order probability distribution to each parameter in order to conduct several types of sensitivity analysis. RESULTS: Two strategies were obtained using two different criteria. When considering only effectiveness, a positive computed tomography (CT) scan must be followed by a transbronchial needle aspiration (TBNA), an endobronchial ultrasound (EBUS), and an endoscopic ultrasound (EUS). When the CT scan is negative, a positron emission tomography (PET), EBUS, and EUS are performed. If the TBNA or the PET is positive, then a mediastinoscopy is performed only if the EBUS and EUS are negative. If the TBNA or the PET is negative, then a mediastinoscopy is performed only if the EBUS and the EUS give contradictory results. When taking into account economic costs, a positive CT scan is followed by a TBNA; an EBUS is done only when the CT scan or the TBNA is negative. This recommendation of performing a TBNA in certain cases should be discussed by the pneumology community because TBNA is a cheap technique that could avoid an EBUS, an expensive test, for many patients. CONCLUSIONS: We have determined the optimal sequence of tests for the mediastinal staging of NSCLC by considering sensitivity, specificity, and the economic cost of each test. The main novelty of our study is the recommendation of performing TBNA whenever the CT scan is positive. Our model is publicly available so that different experts can populate it with their own parameters and re-examine its conclusions. It is therefore proposed as an evidence-based instrument for reaching a consensus. PMID- 26813402 TI - Evaluation of Coronal Leakage Following Different Obturation Techniques and in vitro Evalution Using Methylene Blue Dye Preparation. AB - INTRODUCTION: Coronal and apical leakage still remains one of the most important cause for endodontic failure in spite of the presence of advanced endodontic materials. The cause may attribute to different filling techniques, physical and chemical properties of sealers and presence or absence of smear layer assessment of coronal or apical leakage is used as a research method to compare the sealing ability of different techniques and endodontic materials. AIM: To compare the coronal bacterial leakage using methylene blue in four different obturation techniques after protaper hand instrumentation. MATERIALS AND METHODS: Ninety extracted single-rooted teeth were instrumented to an apical preparation size F3 Protaper hand files. Twenty teeth were randomly obturated with lateral compaction, 20 with vertical compaction, 20 with combination of vertical and lateral compaction and 20 with Thermafil. Ten teeth were used for positive and negative controls (five teeth in each group). Teeth were kept in 100% humidity for 90 days, and then subjected coronally to Proteus vulgaris for 21 days to assess bacterial leakage. After bacterial challenge, methylene blue was placed coronally for another 21 days, and then scoring was done according to depth of dye leakage. Chi-square test was done for statistical analysis. RESULTS: Leakage as observed with combination of vertical and lateral compaction was significantly less than vertical compaction, lateral compaction and thermafil carriers during bacterial challenge. However, when dye was used it also showed statistically significant results with thermafil carriers showing the least leakage in comparison to vertical condensation, lateral condensation and combined groups. CONCLUSION: The study concludes that two different methods i.e. bacterial and dye leakage revealed considerable variation on the same substrate Thus, due to the presence of variability among the results obtained by two different analytical methods used in the present study, the study emphasizes the need for standardization of methods as the lack of standardization hinders the comparison of different endodontic filling techniques. PMID- 26813403 TI - Biomechanical comparison of conventional and anatomical calcaneal plates for the treatment of intraarticular calcaneal fractures - a finite element study. AB - Initial stability is essential for open reduction internal fixation of intraarticular calcaneal fractures. Geometrical feature of a calcaneal plate is influential to its endurance under physiological load. It is unclear if conventional and pre-contoured anatomical calcaneal plates may exhibit differently in biomechanical perspective. A Sanders' Type II-B intraarticular calcaneal fracture model was reconstructed to evaluate the effectiveness of calcaneal plates using finite element methods. Incremental vertical joint loads up to 450 N were exerted on the subtalar joint to evaluate the stability and safety of the calcaneal plates and bony structure. Results revealed that the anatomical calcaneal plate model had greater average structural stiffness (585.7 N/mm) and lower von Mises stress on the plate (774.5 MPa) compared to those observed in the conventional calcaneal plate model (stiffness: 430.9 N/mm; stress on plate: 867.1 MPa). Although both maximal compressive and maximal tensile stress and strain were lower in the anatomical calcaneal plate group, greater loads on fixation screws were found (average 172.7 MPa compared to 82.18 MPa in the conventional calcaneal plate). It was noted that high magnitude stress concentrations would occur where the bone plate bridges the fracture line on the lateral side of the calcaneus bone. Sufficient fixation strength at the posterolateral calcaneus bone is important for maintaining subtalar joint load after reduction and fixation of a Sanders' Type II-B calcaneal fracture. In addition, geometrical design of a calcaneal plate should worth considering for the mechanical safety in practical usage. PMID- 26813405 TI - Awards in Transplantation Science Recognize the Best Manuscripts Published in Transplantation. PMID- 26813406 TI - Organ Transplantation in Sweden. PMID- 26813404 TI - Comparison of laparoscopic and open cystectomy for bladder cancer: a single center of 110 cases report. AB - PURPOSE: We compared the operative time, complications, blood loss, total cost, and hospital days of laparoscopic cystectomy vs. open cystectomy for bladder cancer. MATERIALS AND METHODS: This retrospective, nonrandomized study was conducted between January 2004 and March 2011 on 110 patients (17 women and 93 men) who underwent radical cystectomy for bladder cancer. A total of 45 cystectomies were performed laparoscopically and 65 by open surgery. Mean patient age was 62.9+/-10.4 years. The age, gender, American Society of Anesthesiologists score, histopathological results etc. were reviewed in this article. RESULTS: Intraoperative blood loss was significantly lower in the laparoscopic surgery group (821+/-776 vs. 1112+/-706 mL, P=0.044) while operative time was significantly lower in the open surgery group (376+/-90 vs. 445+/-119 min, P=0.001). The total costs were also significantly lower in the open surgery group 51,726+/-13,589 yuan (about $8000) vs. 63,053+/-19,378 yuan (about $10,000), P<0.001). There was no statistically significant difference in complication rates, postoperative days in hospital between the two groups. CONCLUSIONS: Laparoscopic cystectomy can reduce intraoperative blood loss significantly. Open cystectomy requires less operative time and has a lower cost than laparoscopic cystectomy for bladder cancer. There was no statistically significant difference in postoperative complication rates in the hospital between the two groups. PMID- 26813408 TI - Identity Crisis. PMID- 26813401 TI - A survey of best practices for RNA-seq data analysis. AB - RNA-sequencing (RNA-seq) has a wide variety of applications, but no single analysis pipeline can be used in all cases. We review all of the major steps in RNA-seq data analysis, including experimental design, quality control, read alignment, quantification of gene and transcript levels, visualization, differential gene expression, alternative splicing, functional analysis, gene fusion detection and eQTL mapping. We highlight the challenges associated with each step. We discuss the analysis of small RNAs and the integration of RNA-seq with other functional genomics techniques. Finally, we discuss the outlook for novel technologies that are changing the state of the art in transcriptomics. PMID- 26813409 TI - New HCV Therapies and Liver Transplantation. PMID- 26813410 TI - Gauke Kootstra, PhD. [Corrected]. PMID- 26813412 TI - Meta-analysis of the COMT Val158Met polymorphism in major depressive disorder: the role of gender. AB - OBJECTIVES: Many studies have reported an association of the COMT Val158Met polymorphism and major depressive disorder (MDD), although with conflicting results. The role of gender is a possible modulator. To overcome the problem of poor sample size detecting genes of small effect, we perform a meta-analysis of the current literature, investigating the influence of the COMT Val158Met polymorphism on the pathogenesis of MDD, with a major focus on the effect of gender. METHODS: Out of 977 retrieved articles, 21 included case-control studies allowed the analysis of 9005 patients with MDD and 12,095 controls. Allelic and genotypic pooled odds ratios (OR) were calculated for the total sample and gender subgroups. RESULTS: In the absence of publication bias, allelic and genotypic analyses showed no significant association in the total sample, as well as in gender-specific subgroups. Sensitivity analysis did not alter the ORs. CONCLUSIONS: The results imply a complex nature of the genotype * phenotype interaction. Further studies of the COMT gene or the locus remain to be justified given the important positional and functional relevance and the plethora of gender-specific findings. A possible way to further dissect this topic is shifting the focus to gene-based or genome-wide analyses of intermediate phenotypes. PMID- 26813413 TI - Role of the electric field in selective ion filtration in nanostructures. AB - Nafion has received great attention as a proton conductor that can block negative ions. Here, we report the effect of a Nafion coating on an anodic aluminium oxide (AAO) nanoporous membrane on its function of ion rejection and filtering depending on the electric field. In our experiments, Nafion, once coated, was used to repel the negative ions (anions) from the coated surface, and then selectively allowed positive ions (cations) to pass through the nanopores in the presence of an electric field. To demonstrate the proof-of-concept validation, we coated Nafion solution onto the surface of AAO membranes with 20 nm nanopores average diameter at different solution concentration levels. Vacuum filtration methods for Nafion coating were vertically applied to the plane of an AAO membrane. An electric field was then applied to the upper surface of the Nafion coated AAO membrane to investigate if ion rejection and filtering was affected by the presence of the electric field. Both anions and cations could pass through the AAO nanopores without an electric field applied. However, only cations could well pass through the AAO nanopores under an electric field, thus effectively blocking anions from passing through the nanopores. This result shows that ion filtration of electrons has been selectively performed while the system also works as a vital catalyst in reactivating Nafion via electrolysis. A saturated viscosity ratio of Nafion solution for the coating was also determined. We believe that this approach is potentially beneficial for better understanding the fundamentals of selective ion filtration in nanostructures and for promoting the use of nanostructures in potential applications such as ion-based water purification and desalination system at the nanoscale in a massively electrically integrated format. PMID- 26813411 TI - Multi-parallel qPCR provides increased sensitivity and diagnostic breadth for gastrointestinal parasites of humans: field-based inferences on the impact of mass deworming. AB - BACKGROUND: Although chronic morbidity in humans from soil transmitted helminth (STH) infections can be reduced by anthelmintic treatment, inconsistent diagnostic tools make it difficult to reliably measure the impact of deworming programs and often miss light helminth infections. METHODS: Cryopreserved stool samples from 796 people (aged 2-81 years) in four villages in Bungoma County, western Kenya, were assessed using multi-parallel qPCR for 8 parasites and compared to point-of-contact assessments of the same stools by the 2-stool 2 slide Kato-Katz (KK) method. All subjects were treated with albendazole and all Ascaris lumbricoides expelled post-treatment were collected. Three months later, samples from 633 of these people were re-assessed by both qPCR and KK, re-treated with albendazole and the expelled worms collected. RESULTS: Baseline prevalence by qPCR (n = 796) was 17 % for A. lumbricoides, 18 % for Necator americanus, 41 % for Giardia lamblia and 15% for Entamoeba histolytica. The prevalence was <1% for Trichuris trichiura, Ancylostoma duodenale, Strongyloides stercoralis and Cryptosporidium parvum. The sensitivity of qPCR was 98% for A. lumbricoides and N. americanus, whereas KK sensitivity was 70% and 32%, respectively. Furthermore, qPCR detected infections with T. trichiura and S. stercoralis that were missed by KK, and infections with G. lamblia and E. histolytica that cannot be detected by KK. Infection intensities measured by qPCR and by KK were correlated for A. lumbricoides (r = 0.83, p < 0.0001) and N. americanus (r = 0.55, p < 0.0001). The number of A. lumbricoides worms expelled was correlated (p < 0.0001) with both the KK (r = 0.63) and qPCR intensity measurements (r = 0.60). CONCLUSIONS: KK may be an inadequate tool for stool-based surveillance in areas where hookworm or Strongyloides are common or where intensity of helminth infection is low after repeated rounds of chemotherapy. Because deworming programs need to distinguish between populations where parasitic infection is controlled and those where further treatment is required, multi-parallel qPCR (or similar high throughput molecular diagnostics) may provide new and important diagnostic information. PMID- 26813414 TI - Protein Counting in Single Cancer Cells. AB - The cell is the basic unit of biology and protein expression drives cellular function. Tracking protein expression in single cells enables the study of cellular pathways and behavior but requires methodologies sensitive enough to detect low numbers of protein molecules with a wide dynamic range to distinguish unique cells and quantify population distributions. This study presents an ultrasensitive and automated approach for quantifying phenotypic responses with single cell resolution using single molecule array (SiMoA) technology. We demonstrate how prostate specific antigen (PSA) expression varies over several orders of magnitude between single prostate cancer cells and how PSA expression shifts with genetic drift. Single cell SiMoA introduces a straightforward process that is capable of detecting both high and low protein expression levels. This technique could be useful for understanding fundamental biology and may eventually enable both earlier disease detection and targeted therapy. PMID- 26813415 TI - Synthesis of Peptides by Silver-Promoted Coupling of Carboxylates and Thioamides: Mechanistic Insight from Computational Studies. AB - The mechanism of the recently described N->C direction peptide synthesis through silver-promoted coupling of N-protected amino acids with thioacetylated amino esters was explored by using density functional theory. Calculation of the potential energy surfaces for various pathways revealed that the reaction proceeds through silver-assisted addition of the carboxylate to the thioamide, which is followed by deprotonation and silver-mediated extrusion of sulfur as Ag2 S. The resulting isoimide is the key intermediate, which subsequently rearranges to an imide through a concerted pericyclic [1,3]-acyl shift (O-sp(2) N 1,3-acyl migration). The proposed mechanism clearly emphasises the requirement of two equivalents of Ag(I) and basic reaction conditions, which is in full agreement with the experimental findings. Alternative rearrangement pathways involving only one equivalent of Ag(I) or through O-sp(3) N 1,3-acyl migration can be excluded. The computations further revealed that peptide couplings involving thioformamides require significant conformational changes in the intermediate isoformimide, which slow down the rearrangement process. PMID- 26813416 TI - Alcoholic Liver Disease and Hepatitis C Chronic Infection. AB - Alcoholic and virus C hepatitis currently represent the main causes of chronic liver disease worldwide. Every year many people die and are subjected to complex hospitalization and medical assistance due to these pathologies. Alcoholic liver disease and hepatitis C virus chronic infection are often present in the same patient. These two pathologies sinergically act in determining the onset and progression of liver damage that, from the chronic hepatitis staging, may rapidly progress to fibrosis, cirrhosis and hepatocellular carcinoma. In this review we analysed physiopathological aspects and biomolecular interactions that relate ethanol and hepatitis C virus in determining liver damage; moreover we took into account the effect on the natural history of liver disease deriving from the co presence of these pathologies. Therefore we paid particular attention to the ability of ethanol and hepatitis C virus to in inducing oxidative stress or lipid accumulation, and analyzed the basic mechanisms of fibrogenesis that both diseases have got, amplified by their co-presence in the same patient. Finally we paid attention to the oncogenetic mechanisms inducing hepatocellular carcinoma and variability of response to antiviral therapy that derives from alcohol abuse in a subject affected by C hepatitis. PMID- 26813417 TI - Survival of Root-filled Teeth in the Swedish Adult Population. AB - INTRODUCTION: The aim was to assess survival in the Swedish population of teeth treated by nonsurgical root canal treatment during 2009. METHODS: Data from the Swedish Social Insurance Agency were analyzed by Kaplan-Meier analysis to assess cumulative tooth survival during a period of 5-6 years of all teeth that were root-filled during 2009. RESULTS: In 2009, 248,299 teeth were reported as root filled. The average age of the patients at the time of the root filling was 55 years (range, 20-102 years). The teeth most frequently root-filled were the maxillary and mandibular first molars. During the 5- to 6-year period 25,228 of the root-filled teeth (10.2%) were reported to have been extracted; thus 223,071 teeth (89.8%) survived. Tooth survival was highest in the youngest age group (93.2%). The highest survival (93.0%) was for the mandibular premolars, and the lowest (87.5%) was for the mandibular molars. Teeth restored with indirect restorations within 6 months of the root filling had higher survival rates (93.1%) than those restored with a direct filling (89.6%). CONCLUSIONS: In the adult population of Sweden, teeth that are root-filled by general practitioners under the tax-funded Swedish Social Insurance Agency have a 5- to 6-year survival rate of approximately 90%. PMID- 26813418 TI - Uncontrolled Removal of Dentin during In Vitro Ultrasonic Irrigant Activation. AB - INTRODUCTION: The aim of this study was to evaluate uncontrolled removal of dentin during in vitro ultrasonic irrigant activation in prepared root canals using 2 different files. METHODS: Fifty-four human single-rooted teeth with straight root canals were prepared to size 35/.06 taper. The specimens were randomly allocated to 3 groups (n = 18). Two milliliters of 2% sodium hypochlorite was delivered 3 times to each root canal by a syringe and an open ended needle. After each delivery, the irrigant was ultrasonically activated for 10 seconds at 35% power either by a size 15 ultrasonic K-file (group A) or a size 20 Irrisafe file (Acteon Satelec, Merignac, France) (group B) placed at 2 mm short of the working length. The irrigant in the control specimens (group C) was not activated. Specimens were scanned by micro-computed tomographic imaging at 10 MUm voxel size before preparation, after preparation, and after the final irrigation/activation sequence. Scans were coregistered and segmented, and the amount of dentin removed during the final step was quantified by morphologic operations. Results were analyzed by nonparametric statistical tests. The level of significance was set to P < .05. RESULTS: Defects with a maximum depth of 0.09 mm and 0.07 mm were identified in groups A and B, respectively. Both ultrasonic files removed significantly more dentin than irrigant delivery in the control group (P <= .005). K-files removed significantly more dentin than Irrisafe files in the apical third (P = .001). CONCLUSIONS: Ultrasonic irrigant activation may result in uncontrolled removal of dentin in straight root canals and at manufacturer-recommended power settings. PMID- 26813419 TI - Sequence features associated with the cleavage efficiency of CRISPR/Cas9 system. AB - The CRISPR-Cas9 system has recently emerged as a versatile tool for biological and medical research. In this system, a single guide RNA (sgRNA) directs the endonuclease Cas9 to a targeted DNA sequence for site-specific manipulation. In addition to this targeting function, the sgRNA has also been shown to play a role in activating the endonuclease activity of Cas9. This dual function of the sgRNA likely underlies observations that different sgRNAs have varying on-target activities. Currently, our understanding of the relationship between sequence features of sgRNAs and their on-target cleavage efficiencies remains limited, largely due to difficulties in assessing the cleavage capacity of a large number of sgRNAs. In this study, we evaluated the cleavage activities of 218 sgRNAs using in vitro Surveyor assays. We found that nucleotides at both PAM-distal and PAM-proximal regions of the sgRNA are significantly correlated with on-target efficiency. Furthermore, we also demonstrated that the genomic context of the targeted DNA, the GC percentage, and the secondary structure of sgRNA are critical factors contributing to cleavage efficiency. In summary, our study reveals important parameters for the design of sgRNAs with high on-target efficiencies, especially in the context of high throughput applications. PMID- 26813420 TI - Borrelia bissettiae sp. nov. and Borrelia californiensis sp. nov. prevail in diverse enzootic transmission cycles. AB - Two species of the genus Borrelia, Borrelia bissettiae sp. nov. and Borrelia californiensis sp. nov., were first described by Postic and co-workers on the basis of genetic analyses of several loci. Multilocus sequence analysis of eight housekeeping loci confirmed that these two Borrelia genomospecies are distinct members of the Borrelia burgdorferi sensu lato complex. B. bissettiae sp. nov. was initially described in transmission cycles involving Neotoma fuscipes wood rats and Ixodes pacificus ticks in California, and Neotoma mexicana and Ixodes spinipalpis in Colorado. The preferred host of B. californiensis sp. nov. appears to be the California kangaroo rat, Dipodomys californicus; Ixodes jellisoni, I. spinipalipis and I. pacificus ticks are naturally infected with it. Thus, the ecological associations of the two genomospecies and their genetic distance from all other known Borrelia genomospecies species justify their description as separate genomospecies: B. bissettiae sp. nov. (type strain DN127T = DSM 17990T = CIP 109136T) and B. californiensis (type strain CA446T = DSM 17989T = ATCC BAA 2689T). PMID- 26813421 TI - First detection of koi herpesvirus from koi, Cyprinus carpio L. experiencing mass mortalities in Iran: clinical, histopathological and molecular study. AB - Koi herpesvirus (KHV) is the aetiological agent of an emerging disease (KHVD) associated with mass mortalities in koi and common carp and reported from at least 30 countries. We report the first detection of KHV from koi in Iran using clinical, histopathological and molecular studies. KHV-infected fish showed reduced swimming activity, sunken eyes and increased mucus production on skin and fins. On post-mortem examination, gill necrosis was observed in the majority of fish. Histopathologically, the gill showed diffuse necrosis of the branchial epithelial cells. Margination of chromatin was detected in gills, kidney, heart, spleen, intestine and brain. In addition, sequence analyses of the TK gene, ORF 136 and marker I and II, demonstrates that Iranian KHV isolates were identical and classified as variant A1 of TUSMT1 (J strain) and displayed the I(++) II(+) allele of this Asian genotype. PMID- 26813422 TI - Impact of Video Based Learning on the Perfomance of Post Graduate Students in Biostatistics: A Retrospective Study. AB - INTRODUCTION: Education, being a process of knowledge transfer always has advances which are generally on par with the discovery of newer technologies. Currently, most of the education process has shifted away from the conventional black board towards the usage of more student friendly technologies. This leads us to the aim of this study, which is to analyse the impact of video based learning on the performance of dental post graduate students in their biostatistics course. MATERIALS AND METHODS: A new video based discussion method was followed to teach biostatistics to MDS postgraduate students in 2013 (test group, n=44). The performance of these students were compared to a historical cohort of scores obtained by students of the 2012 batch (control group, n=44) who underwent a traditional lecture based teaching for the same course. The scores obtained by the students in their undergraduate board exams were compared to test for difference in academic aptitude of the students in the two groups. RESULTS: The mean exam score of the test group was significantly higher (66.60+/-8.92) when compared to the control group (53.48+/-8.38); (p < 0.001 Independent Sample t-test). There was no significant difference in the overall academic performance of the students from both groups (test group mean academic performance was 61.47+/-4.86 and control group was 63.19+/-4.69. CONCLUSION: The results of this study suggest that video based discussion based teaching is more effective in training postgraduate dental students in biostatistics. PMID- 26813423 TI - [Discussion on the road of liver cancer prevention and treatment in China]. PMID- 26813424 TI - [Research progress in improving the efficacy of surgical treatment of primary liver cancer]. PMID- 26813425 TI - [Practice strategy of liver transplantation for hepatocellular carcinoma]. PMID- 26813426 TI - [Stereotactic body radiation therapy for hepatocellular carcinoma]. PMID- 26813427 TI - [Interventional treatment of primary liver cancer in China: status quo and perspectives]. PMID- 26813428 TI - [Further discussion on image-guided standardized radiofrequency ablation therapy for hepatocellular carcinoma]. PMID- 26813429 TI - [Advances in clinical research of liver metastases from colorectal cancer]. PMID- 26813430 TI - [Silencing HMGB1 expression by lentivirus-mediated small interfering RNA (siRNA) inhibits the proliferation and invasion of colorectal cancer LoVo cells in vitro and in vivo]. AB - OBJECTIVE: To inquire into the influence of silencing HMGB1 expression by small interfering RNA (siRNA) on cell growth, proliferation, invasion and metastasis of colorectal cancer LoVo cells both in vitro and in vivo. METHODS: Lentivirus mediated HMGB1 siRNA was transfected into LoVo cells to silence the HMGB1 expression. The HMGB1 mRNA and protein expression after siRNA transfection was detected by RT-PCR and Western blot. MTT assay was used to observe the cell proliferation and to draw a growth curve. Cell cycle was measured by flow cytometry. The ability of invasion and speed of cell migration were evaluated by transwell chamber invasion and cell scratch assay. The influence of HMGB1 silencing on the proliferation of LoVo cells in vivo was observed in LoVo tumor bearing nude mice. RESULTS: Lentivirus-mediated siRNA was successfully transfected into colorectal cancer cell line LoVo. The expression of HMGB1 mRNA and protein in the HMGB1-siRNA group were 0.24+/-0.04 and 0.21+/-0.03, respectively. Compared with the HMGB1-siRNA-Neg group (0.82+/-0.13, 1.15+/-0.18) and control group (0.93+/-0.15, 1.21+/-0.20), the difference was significant (P<0.05). MTT assay showed that the cell proliferation in the HMGB1-siRNA group was significantly inhibited when compared with that in the HMGB1-siRNA-Neg group and control group (P<0.05). Flow cytometry showed that the proliferation index (PI) of HMGB1-siRNA group was 38.27+/-1.32, significantly lower than 54.66+/-1.74 in the HMGB1-siRNA-Neg group and 57.43+/-1.29 in the control group (P<0.05). The transwell assay showed that the number of penetrated cells in the HMGB1-siRNA group was 14.0+/-3.5, significantly lower than 51.0+/-6.7 in the HMGB1-siRNA-Neg group and 68.0+/-5.3 in the control group (P<0.05). Similarly, the scrape wound recovered significantly slower in the HMGB1-siRNA group (83.61+/-23.21) um than that in the other two groups (202.86+/-46.46) um and (214.58+/-57.38) um(P<0.05). The nude mouse xenograft tumor experiment showed that the final tumor volume was (521+/-34) mm3 in the HMGB1-siRNA group, significantly smaller than that in the HMGB1-siRNA-Neg group of (763+/-46) mm3 and control group of (802+/-51) mm3 (P<0.05). CONCLUSIONS: Lentivirus-mediated HMGBl-siRNA can effectively inhibit the HMGB1 expression in colorectal cancer LoVo cells both in vitro and in vivo. HMGB1 gene silencing can slow the growth of colorectal cancer cells, extend the cell proliferation cycle, decrease their invasion and migration, and significantly inhibit the growth of xenograft tumor in nude mice. PMID- 26813431 TI - [Effect of preoperative transcatheter arterial chemoembolization on the perioperative outcome of patients with hepatocellular carcinoma]. AB - OBJECTIVE: To explore the surgical risk, perioperative outcome and the response of patients with hepatocellular carcinoma (HCC) after preoperative transcatheter arterial chemoembolization (TACE). METHODS: A retrospective case-matched study was conducted to compare the characteristics and corresponding measures of patients in the preoperative TACE group and the control group without TACE. A total of 105 patients (82 patients with selective and dynamic region-specific vascular occlusion to perform hepatectomy for patients with complex hepatocellular carcinoma) was included in this study, in which 35 patients underwent TACE therapy, and a 1:2 matched control group of 70 subjects. RESULTS: The patients of preoperative TACE therapy group had a higher level of gamma glutamyl transpeptidase before operation (119.52+/-98.83) U/L vs. (67.39+/-61.25) U/L (P=0.040). The operation time was longer in the TACE group than that in the control group but with a non-significant difference (232.60+/-95.43) min vs. (218.70+/-75.13) min (P=0.052). The postoperative recovery of liver function and severe complications in the preoperative TACE group were similar to that in the control group (P>0.05). There were no massive hemorrhage, biliary fistula and 30 d death neither in the treatment group and matched control group. CONCLUSIONS: Preoperative TACE therapy has certain negative effect on liver function. It is preferable to use selective and dynamic region-specific vascular occlusion technique during hepatectomy and combine with reasonable perioperative treatment for this group of patients, that can ensure safety of patients and promote their rapid recovery. PMID- 26813432 TI - [Phase II clinical trial of two different modes of administration of the induction chemotherapy for locally advanced nasopharyngeal carcinoma]. AB - OBJECTIVE: To compare the therapeutic effects, toxic side effects and influence on the immune function in patients treated with TPF [docetaxel (DOC) + cisplatin (DDP) + 5-fluorouracil (5-Fu)] induction chronochemotherapy and conventional chemotherapy for locally advanced nasopharyngeal (NPC). METHODS: Seventy patients with locally advanced nasopharyngeal carcinoma were treated in our department at their first visit from April 2013 to December 2013. They were divided randomly into two groups: the chronochemotherapy group (38 patients) and conventional chemotherapy group (32 patients). All of the patients were treated with TPF regimen with 2 cycles of induction chemotherapy in a 21-28-days/cycle. The chronochemotherapy group: DOC: 75 mg/m2, i. v. gtt, d1 (03: 30-04: 30); DDP: 75 mg/m2, 10 am-10 pm, c.i.v, d1-d5; 5-Fu: 750 mg.m(-2).d(-1), 10 pm-10 am, c. i.v., d1-d5, both chemotherapies were administered by intravenous infusion using an automatic electric pump. The conventional chemotherapy group: Both DOC and DDP were administered intravenously at a dose of 75 mg/m2 on d1. 5-Fu was given at a dose of 750 mg/m2 for 24 hours from d1-d5 with continuous infusion in a total of 120 hours. In this procedure, prescribing the conventional intravenous infusion, intensity modulated radiation therapy was used after the induction chemotherapy. The prescribed nasopharyngeal lesion dose (GTVnx) was 69.96 Gy/33 fractions for the T1-T2 nasopharygeal cancer, while 73.92 Gy/33 fractions nasopharynx lesion dose (GTVnx) for the T3-T4 nasopharyngeal cancer. The planning target volume (PTV) of positive lymph node (PTVnd) dose was 69.96 Gy/33 fractions. Concurrent chemoradiotherapy: cisplatin 100 mg/m2, i. v. gtt. d1-d2, and there were two cycles in total and 21 days each cycle. RESULTS: Sixty-six patients were evaluable for the response assessment. There were 36 patients in the chronochemotherapy group and 30 patients in the conventional chemotherapy group. After the induction chemotherapy, no CR case was found in both of the two groups. The PR was 80.6% in the chronochemotherapy group and 50.0% in the conventional chemotherapy group (P=0.009). After concurrent chemoradiotherapy, the CR rate in the chronocheotherapy group was 45.5%, significantly higher than 20.7% in the conventional chemotherapy group (P=0.040). Secondly, the incidence rates of adverse reactions including bone marrow suppression, nausea, vomiting, diarrhea, constipation, oral mucositis, fatigue, anorexia in the chrono-chemotherapy group were significantly lower than that in the conventional group (P<0.05 for all). Finally, compared the two groups, the CD4+ /CD8+ ratio was significantly lower in the chronochemotherapy group than that in the conventional chemotherapy group (P<0.05). The lymphocytes CD19+ and CD4+/CD8+ were decreased and CD3+, CD4+, CD8+, CD16++CD56+ were increased in the chronochemotherapy group, while only CD3+ and CD8+ were increased in the conventional chemotherapy group. CONCLUSIONS: Compared with the conventional chemotherapy, the chronochemotherapy may be more favorable in the treatment of NPC, with a better therapeutic effects and effectiveness than that of conventional chemotherapy after induction chemotherapy, with less side effects, and can improve the immune function in the patients. PMID- 26813433 TI - [Clinical application of MRI-guided puncture of breast microlesions]. AB - OBJECTIVE: To explore the clinical indications of MRI-guided puncture positioning or biopsy, and evaluate the clinical practical value. METHODS: The clinicopathological data of 30 patients who underwent MRI-guided puncture positioning or biopsy were retrospectively collected and analyzed, and the patients were followed up after operation. RESULTS: The success rate of MRI guided puncture was 100%. After biopsy or surgical resection, the pathological diagnoses were as follows: 6 cases (20.0%) of invasive carcinoma, 9 cases (30.0%) of ductal carcinoma in suit (DCIS), and 15 cases (50.0%) of benign lesions, and the false negative rate was 0.In the 30 patients, the lesions of 22 patients were not clear and difficult to analyze qualitatively by ultrasound or mammography imaging examination. After MRI-guided puncture positioning or biopsy, the pathological examination showed that 11 cases (50.0%) of them were malignant tumors. MRI examinations indicated as malignant in 21 cases, among them, seven cases were pathologically confirmed as benign pathology, with a false positive rate of 33.3%. MRI examination considered benign in 9 cases, in which one case was pathologically diagnosed as malignant, thus, the false negative rate was 11.1%.In the 30 patients, there were no hematoma, infection and other complications after the puncture. The median follow-up time was 7.5 months. One patient died due to breast cancer metastasis, one patient showed relapse by imaging examination and underwent surgery, one case was lost, and the remaining patients were normal in the regularly follow-up results. CONCLUSIONS: MRI-guided biopsy of breast microlesions is a safe, rapid and accurate diagnostic method. When the ultrasound and mammography can not find clear lesions or the lesions are difficult to analyze qualitatively, MRI-guided puncture positioning or biopsy can be applied to improve early diagnosis and treatment, and reduce false negative rate of breast cancer. PMID- 26813434 TI - [Analysis of the diagnosis and treatment of desmoplastic small round cell tumor]. AB - OBJECTIVE: To explore the clinical diagnostic features and treatment of desmoplastic small round cell tumor (DSRCT), and to improve the understanding and management of this tumor. METHODS: The clinicopathological data of nine patients treated in our hospital from October 2004 to June 2014 were retrospectively analyzed and a review of the literature was made. The clinical manifestations, pathological characteristics, diagnosis and differential diagnosis, treatment and prognosis of this tumor were summarized and analyzed. RESULTS: Nine patients with DSRCT, 5 males and 4 females, with an average age of 21 years (range 8-56 years) were included in this study. Ultrasound examination revealed irregular low density mass shadow in the abdominal cavity. CT examination found that 6 cases had abdominal and retroperitoneal multiple solid tumor nodules, uneven density, and visible low density fluid area. Postoperative pathological examination revealed that the tumor cells were small, mostly elliptic, gathered to form clear structure of nests with clear irregular boundaries. The central portion of large tumor nests often showed necrosis. Scattered fibroblasts and large amount of hyalinization of collagen fibers were seen in the interstitial tissue around the nests. Six patients received laparotomy surgery, however, all failed to resect the tumor completely. Three patients received postoperative chemotherapy, i. e. two cases had carboplatin and paclitaxel chemotherapy, and one case of chemotherapy regimen not specified. Two patients had radiation and chemotherapy (no concrete plan was available). Another case was lost to follow-up. Two of the three patients without surgery received chemotherapy with CAP (cyclophosphamide+adriamycin+carboplatin) and total rectal lesions, pelvic and inguinal lymph nodes, ilium metastases radiation therapy. Another one patient received EP regimen (DDP+VP16) which was then changed into a TP chemotherapy alone. Eight of the nine cases died shortly after surgery, and only one patient treated with chemotherapy alone was still alive after 11 months of follow-up. CONCLUSIONS: Desmoplastic small round cell tumor is a very rare, special type of soft tissue tumor, with very poor prognosis. This tumor may be preliminarily diagnosed according to the imaging characteristics and detection of tumor markers, however, final diagnosis is made by pathology. Surgery is the priority of treatment, combined with complementary radiation and chemotherapy. PMID- 26813435 TI - [Analysis of liver cancer incidence and trend in China]. AB - OBJECTIVE: The national population-based cancer registration data were used to analyze the liver cancer incidence and trend in China, in order to provide advise for making further strategy on liver cancer prevention and control. METHODS: Liver cancer data of 2011 were retrieved from the database of the National Cancer Registry. The incident cases of liver cancer were estimated using age-specific rate by urban or rural areas and gender according to the national population in 2011. Liver cancer incidence data from 22 cancer registries were used to analyze the incidence trend during 2000-2011. RESULTS: The estimates of new cases of liver cancer were about 356 thousand in China in 2011. The incidence rate was 26.39/10(5,) and the age-standardized incidence rates by Chinese standard population and by world population were 19.48/10(5) and 19.10/10(5,) respectively.There was an increasing trend of incidence rate of liver cancer in China during 2000-2011 with an average annual percentage change(AAPC) of 1.0% (95%CI: 0.5%-1.4%), 1.2% (95%CI: 0.7%-1.8%)in urban areas and 1.1% (95%CI: 0.5% 1.8%) in rural areas. After age standardization, the incidence rate was significantly decreased, with an AAPC of -1.8% (95%CI: -2.4% to -1.2%), -1.6% (95%CI: -2.2% to -0.9%) in urban and -1.4% (95%CI: -2.5% to -0.3%) in rural areas. CONCLUSIONS: Liver cancer is a common cancer in China. As changing in people's dietary habits and implementing neonatal HBV vaccination for years, the exposure to risk factors is reducing, and age-standardized incidence rate is decreasing. While cardinal number of population is big and aging population is growing rapidly in the country, trend of incidence rate is increasing, and the burden of liver cancer is still high in China. PMID- 26813436 TI - [Mortality and survival analysis of liver cancer in China]. AB - OBJECTIVE: Based on the cancer registry data to analyze the mortality and survival of liver cancer in China. METHODS: Liver cancer data of 2011 were retrieved from the National Cancer Registry Database.Liver cancer deaths were estimated using age-specific rate by areas and gender according to the national population in 2011. Mortality data from 22 cancer registries during 2000-2011 were used to analyze the mortality trend, and data from 17 cancer registries during 2003-2005 were used for survival analysis. RESULTS: The estimates of liver cancer deaths were about 322 thousand in 2011 with a crude mortality rate of 23.93/10(5).There was an increasing trend of crude mortality rate of liver cancer during 2000-2011 in 22 Chinese cancer registries with an average annual percentage change of 0.7% (95%CI: 0.2%-1.2%), 1.1% in urban and 0.4% in rural areas. After age standardization with Segi's population, the mortality rate was significantly decreased, with an APC of -2.3%, -1.9% in urban and -2.2% in rural populations. The 5-year age standardized relative survival was 10.1% (95%CI: 9.5% to 10.7%), and the 1-, 3- and the 5-year observed survival rates were 27.2%, 12.7%, and 8.9%, respectively. CONCLUSION: Liver cancer is a major cancer threatening people's lives and health in China, and the liver cancer burden is still high. PMID- 26813437 TI - [Liver cancer incidence and mortality data set in China]. PMID- 26813438 TI - The pathobiology of pig-to-primate xenotransplantation: a historical review. AB - The immunologic barriers to successful xenotransplantation are related to the presence of natural anti-pig antibodies in humans and non-human primates that bind to antigens expressed on the transplanted pig organ (the most important of which is galactose-alpha1,3-galactose [Gal]), and activate the complement cascade, which results in rapid destruction of the graft, a process known as hyperacute rejection. High levels of elicited anti-pig IgG may develop if the adaptive immune response is not prevented by adequate immunosuppressive therapy, resulting in activation and injury of the vascular endothelium. The transplantation of organs and cells from pigs that do not express the important Gal antigen (alpha1,3-galactosyltransferase gene-knockout [GTKO] pigs) and express one or more human complement-regulatory proteins (hCRP, e.g., CD46, CD55), when combined with an effective costimulation blockade-based immunosuppressive regimen, prevents early antibody-mediated and cellular rejection. However, low levels of anti-non-Gal antibody and innate immune cells and/or platelets may initiate the development of a thrombotic microangiopathy in the graft that may be associated with a consumptive coagulopathy in the recipient. This pathogenic process is accentuated by the dysregulation of the coagulation-anticoagulation systems between pigs and primates. The expression in GTKO/hCRP pigs of a human coagulation-regulatory protein, for example, thrombomodulin, is increasingly being associated with prolonged pig graft survival in non-human primates. Initial clinical trials of islet and corneal xenotransplantation are already underway, and trials of pig kidney or heart transplantation are anticipated within the next few years. PMID- 26813439 TI - 70-fs mode-locked erbium-doped fiber laser with topological insulator. AB - Femtosecond optical pulses have applications in optical communication, astronomical frequency combs, and laser spectroscopy. Here, a hybrid mode-locked erbium-doped fiber (EDF) laser with topological insulator (TI) is proposed, for the first time to our best knowledge. The pulsed laser deposition (PLD) method is employed to fabricate the fiber-taper TI saturable absorber (TISA). By virtue of the fiber-taper TISA, the hybrid EDF laser is passively mode-locked using the nonlinear polarization evolution (NPE), and emits 70 fs pulses at 1542 nm, whose 3 dB spectral width is 63 nm with a repetition rate and transfer efficiency of 95.4 MHz and 14.12%, respectively. Our experiments indicate that the proposed hybrid mode-locked EDF lasers have better performance to achieve shorter pulses with higher power and lower mode-locking threshold in the future. PMID- 26813440 TI - Global inorganic nitrogen dry deposition inferred from ground- and space-based measurements. AB - Atmospheric nitrogen (N) dry deposition is an important component in total N deposition. However, uncertainty exists in the assessment of global dry deposition. Here, we develop empirical models for estimating ground N concentrations using NO2 satellite measurements from the Ozone Monitoring Instrument (OMI) and ground measurements from 555 monitoring sites. Global patterns and trends in the fluxes of NO2, HNO3, NH4(+), and NO3(-) were assessed for 2005-2014. Moreover, we estimated global NH3 dry deposition directly using data from 267 monitoring sites. Our results showed that East Asia, the United States, and Europe were important regions of N deposition, and the total annual amount of global inorganic N deposition was 34.26 Tg N. The dry deposition fluxes were low in Africa and South America, but because of their large area, the total amounts in these regions were comparable to those in Europe and North America. In the past decade, the western United States and Eurasia, particularly eastern China, experienced the largest increases in dry deposition, whereas the eastern United States, Western Europe, and Japan experienced clear decreases through control of NOx and NH3 emissions. These findings provide a scientific background for policy-makers and future research into global changes. PMID- 26813441 TI - Combined QM(DFT)/MM molecular dynamics simulations of the deamination of cytosine by yeast cytosine deaminase (yCD). AB - Extensive combined quantum mechanical (B3LYP/6-31G*) and molecular mechanical (QM/MM) molecular dynamics simulations have been performed to elucidate the hydrolytic deamination mechanism of cytosine to uracil catalyzed by the yeast cytosine deaminase (yCD). Though cytosine has no direct binding to the zinc center, it reacts with the water molecule coordinated to zinc, and the adjacent conserved Glu64 serves as a general acid/base to shuttle protons from water to cytosine. The overall reaction consists of several proton-transfer processes and nucleophilic attacks. A tetrahedral intermediate adduct of cytosine and water binding to zinc is identified and similar to the crystal structure of yCD with the inhibitor 2-pyrimidinone. The rate-determining step with the barrier of 18.0 kcal/mol in the whole catalytic cycle occurs in the process of uracil departure where the proton transfer from water to Glu64 and nucleophilic attack of the resulting hydroxide anion to C2 of the uracil ring occurs synchronously. (c) 2016 Wiley Periodicals, Inc. PMID- 26813442 TI - The Effect of Protein Mass Modulation on Human Dihydrofolate Reductase. AB - Dihydrofolate reductase (DHFR) from Escherichia coli has long served as a model enzyme with which to elucidate possible links between protein dynamics and the catalyzed reaction. Such physical properties of its human counterpart have not been rigorously studied so far, but recent computer-based simulations suggest that these two DHFRs differ significantly in how closely coupled the protein dynamics and the catalyzed C-H -> C hydride transfer step are. To test this prediction, two contemporary probes for studying the effect of protein dynamics on catalysis were combined here: temperature dependence of intrinsic kinetic isotope effects (KIEs), which are sensitive to the physical nature of the chemical step, and protein mass modulation, which slows down fast dynamics (femto to picosecond time scale) throughout the protein. The intrinsic H/T KIEs of human DHFR, like those of E. coli DHFR, are shown to be temperature-independent in the range from 5 to 45 degrees C, indicating fast sampling of donor and acceptor distances (DADs) at the reaction's transition state (or tunneling ready state, TRS). Mass modulation of these enzymes through isotopic labeling with (13)C, (15)N, and (2)H at nonexchangeable hydrogens yields an 11% heavier enzyme. The additional mass has no effect on the intrinsic KIEs of the human enzyme. This finding indicates that the mass modulation of the human DHFR affects neither DAD distribution nor the DAD's conformational sampling dynamics. Furthermore, reduction in the enzymatic turnover number and the dissociation rate constant for the product indicate that the isotopic substitution affects kinetic steps that are not the catalyzed C-H -> C hydride transfer. The findings are discussed in terms of fast dynamics and their role in catalysis, the comparison of calculations and experiments, and the interpretation of isotopically modulated heavy enzymes in general. PMID- 26813444 TI - Comment on the case report "Limb deformity in a newborn. Is rifampicin just an innocent bystander?" by Kalayci et al. PMID- 26813443 TI - Long-term cumulative survival and mechanical complications of single-tooth Ankylos Implants: focus on the abutment neck fractures. AB - PURPOSE: To evaluate the cumulative survival rate (CSR) and mechanical complications of single-tooth Ankylos(r) implants. MATERIALS AND METHODS: This was a retrospective clinical study that analyzed 450 single Ankylos(r) implants installed in 275 patients between December 2005 and December 2012. The main outcomes were survival results CSR and implant failure) and mechanical complications (screw loosening, fracture, and cumulative fracture rate [CFR]). The main outcomes were analyzed according to age, sex, implant length or diameter, bone graft, arch, and position. RESULTS: The 8-year CSR was 96.9%. Thirteen (2.9%) implants failed because of early osseointegration failure in 3, marginal bone loss in 6, and abutment fracture in 4. Screw loosening occurred in 10 implants (2.2%), and 10 abutment fractures occurred. All abutment fractures were located in the neck, and concurrent screw fractures were observed. The CSR and rate of screw loosening did not differ significantly according to factors. The CFR was higher in middle-aged patients (5.3% vs 0.0% in younger and older patients); for teeth in a molar position (5.8% vs 0.0% for premolar or 1.1% for anterior position); and for larger-diameter implants (4.5% for 4.5 mm and 6.7% for 5.5 mm diameter vs 0.5% for 3.5 mm diameter) (all P<.05). CONCLUSION: The Ankylos(r) implant is suitable for single-tooth restoration in Koreans. However, relatively frequent abutment fractures (2.2%) were observed and some fractures resulted in implant failures. Middle-aged patients, the molar position, and a large implant diameter were associated with a high incidence of abutment fracture. PMID- 26813445 TI - Comment on "The correlation of Helicobacter pylori with the development of cholelithiasis and cholecystitis: the results of a prospective clinical study in Saudi Arabia". PMID- 26813446 TI - Comment on "Tegafur gimeracil oter combined with oxaliplatin for advanced colorectal cancer." Is it cost effectiveness? PMID- 26813447 TI - Bilateral hypertrophy of masseteric and temporalis muscles, our fifteen patients and review of literature. AB - OBJECTIVE: The association of bilateral hypertrophy of temporalis and masseteric muscles is a rare clinical entity. The origin of the condition is unclear, causing cosmetic problems, pain, and functional impairment. PATIENTS AND METHODS: In this paper we analyzed 15 patients treated at the Department of Maxillo-Facial Surgery of the University of Naples Federico II, from 2000 to 2013, for temporalis and/or masseteric muscle hypertrophy, and in particular, a rare case of a patient with a marked bilateral swelling of the temporalis and masseteric region, in conjunction with a review of the literature. RESULTS: Fourteen patients have not any kind of postoperatively problems. The last patient had been aware of the swelling for many years and complained of recurrent headaches. We adopted a new protocol fort this patients and the patient was very pleased with the treatment results, and reported a reduction in headaches and a continuation of his well-being, in addition to greater self-confidence. The last follow-up was performed three years after the first treatment, and the patient showed a complete resolution of his symptoms, and just a small increase of the swelling. CONCLUSIONS: The treatment of temporalis and masseteric hypertrophy with Botulin toxin could be an effective option compared to conservative treatment or surgical intervention, although the review of the literature shows that this is only a temporary treatment. In fact, surgery still remains the best option. The treatment must be repeated every 4/6 months for 2-3 consecutive years before having stable benefits. To overcome this problem, an association with a bite treatment allowed us to achieve more lasting and more stable results over time without a recurrence of symptoms between the treatments. Furthermore, this association has enabled us to obtain a more rapid reduction of the hypertrophy. PMID- 26813448 TI - A longitudinally split rabbit segmental gracilis to simulate penile erectile function: anatomic basis and animal models. AB - OBJECTIVE: The gracilis was once applied in reconstructing erectile function but its appearance was bulky. We aimed to design a model meeting the requirements of both reducing volume and retaining function. MATERIALS AND METHODS: The gracilis muscles of 6 rabbits were harvested, applied colorful vascular perfusion and modified Sihler's intramuscular nerve staining. According to their intramuscular nerves and blood vessels, 9 rabbit right gracilis muscles were then longitudinally split into two halves. The anterior muscle bundle was selected as the functional unit and blood supply. RESULTS: The intramuscular nerves and vessels were simultaneously presented on a same specimen. Their relationship suggested gracilis muscle to be composed of two relatively independent subunits. The reconstructed penis survived well, simulating erectile action satisfactorily. DISCUSSION: The penis model reconstructed with longitudinally split rabbit segmental gracilis myocutaneous flap had met the requirements of both restoring erectile function and improving the appearance. PMID- 26813449 TI - The evaluation of hormonal and psychological parameters that affect bone mineral density in postmenopausal women. AB - OBJECTIVE: In this study we aimed to investigate the relationships between serum levels of DHEAS, reproductive hormones and low bone mineral density (BMD) in postmenopausal women. We also examined the relationship between psychological status of patients and their BMD results. PATIENTS AND METHODS: This study included postmenopausal female patients. BMD measurements were performed with dual-energy X-ray absorptiometry (DEXA). Psychological assessments of all cases were performed using the Hamilton Anxiety and Hamilton Depression scales. All patients provided fasting venous blood samples in order to determine serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and DHEAS. RESULTS: There were 33 cases (45.2%) with normal BMD levels and 40 cases (54.8%) with abnormal BMD levels (osteopenia and osteoporosis). DHEAS levels did not show any statistically significant difference according to BMD results (p = 0.431). The Hamilton Anxiety and Depression scores also did not show statistically significant differences in accordance with the BMD results (p = 0.889 and p = 0.706, respectively). CONCLUSIONS: According to our results, anxiety, depression and circulating DHEAS levels are not significantly associated with low levels of BMD, particularly at osteopenic levels. So these parameters are not useful for clinical practice in patients with low BMD in the middle-aged postmenopausal women. PMID- 26813450 TI - Effects of vitamin D levels on asthma control and severity in pre-school children. AB - OBJECTIVE: Prevalence of asthma and vitamin D deficiency has been increasing and leading to significant morbidities. This study aimed to compare the vitamin D levels in the pre-school children with asthma and in healthy controls and to assess the relationship between vitamin D levels and asthma clinical parameters and control. PATIENTS AND METHODS: Vitamin D [25(OH)D3] levels were measured in 102 pre-school children, aged 1-4 years with asthma and 102 healthy controls in winter. The patients with asthma were grouped according to serum vitamin D levels as sufficient, insufficient and deficient. Asthma control was classified according to the Global Initiative for Asthma (GINA) guidelines and the Test for Respiratory and Asthma Control in Kids (TRACK) in 1-4 years-old children. RESULTS: Serum vitamin D levels were 22.64 (9.96) ng/ml in the asthma group and 32.11 (14.74) ng/ml in the control group (p = 0.001). Total number of exacerbations during the previous year were significantly lower in the vitamin D sufficient group, compared to the deficient and insufficient groups (p = 0.03). Frequency of patients with controlled asthma was higher in the sufficient group compared to the deficient and insufficient groups (p = 0.001 and p = 0.001, respectively). There was a positive correlation between serum vitamin D levels and asthma control. CONCLUSIONS: The frequency of vitamin D deficiency and insufficiency was higher in children with asthma, compared to the controls. Therefore, we suggest that lower levels of vitamin D are associated with poor asthma control and increased asthma severity. PMID- 26813451 TI - Effect of acetazolamide on post-NIV metabolic alkalosis in acute exacerbated COPD patients. AB - OBJECTIVE: Non-invasive ventilation (NIV) is an effective treatment in patients with acute exacerbation of COPD (AECOPD). However, it may induce post-hypercapnic metabolic alkalosis (MA). This study aims to evaluate the effect of acetazolamide (ACET) in AECOPD patients treated with NIV. PATIENTS AND METHODS: Eleven AECOPD patients, with hypercapnic respiratory failure and MA following NIV, were treated with ACET 500 mg for two consecutive days and compared to a matched control group. Patients and controls were non invasively ventilated in a bilevel positive airway pressure (BiPAP) mode to a standard maximal pressure target of 15-20 cmH2O. RESULTS: ACET intra-group analysis showed a significant improvement for PaCO2 (63.9 +/- 9.8 vs. 54.9 +/- 8.3 mmHg), HCO3- (43.5 +/- 5.9 vs. 36.1 +/- 5.4 mmol/L) and both arterial pH (7.46 +/- 0.06 vs. 7.41 +/- 0.06) and urinary pH (6.94 +/- 0.77 vs 5.80 +/- 0.82), already at day 1. No significant changes in endpoints considered were observed in the control group at any time-point. Inter group analysis showed significant differences between changes in PaCO2 and HCO3- (delta), both at day 1 and 2. Furthermore, the length of NIV treatment was significantly reduced in the ACET group compared to controls (6 +/- 8 vs. 19 +/- 19 days). No adverse events were recorded in the ACET and control groups. CONCLUSIONS: ACET appears to be effective and safe in AECOPD patients with post NIV MA. PMID- 26813452 TI - Serum angiopoietin-like 4 is over-expressed in COPD patients: association with pulmonary function and inflammation. AB - OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is both a pulmonary and systematic disease, which will cause abnormal expression of some circulating factors. Angiopoietin-like protein 4 (ANGPTL4) has been reported to play important role in inflammatory responses and several diseases. However, whether it contributes to COPD is an open question. The aim of this study is to explore the potential relationship between ANGPTL4 and COPD. PATIENTS AND METHODS: In this study, circulating levels of ANGPTL4, C-reactive protein (CRP), adiponectin, tumor necrosis factor (TNF)-alpha, matrix metalloproteinase (MMP)-9 and monocyte chemotactic protein (MCP)-1 in 73 COPD patients and 40 healthy volunteers were investigated using multiplex enzyme-linked immunosorbent assay Kits. Then, we analyzed the correlations between ANGPTL4 with other inflammatory mediators and pulmonary function. RESULTS: Serum ANGPTL4 levels were significantly elevated in COPD patients compared with healthy controls (122.86 +/- 38.59 ng/mL versus 99.03 +/- 31.84 ng/mL, p = 0.001). Besides, serum ANGTPL4 levels were much higher in ever-smokers with COPD than in never-smokers with COPD (131.71 +/- 32.92 ng/mL versus 113.25 +/- 42.34 ng/mL, p = 0.03). More importantly, the concentrations of circulating ANGPLT4 correlated inversely with forced expiratory volume in 1 second (FEV1) % predicted, an index of lung function in COPD (r = -0.450, p < 0.001) and in all participants (r = -0.369, p < 0.001), while correlated positively with CRP (r = 0.312, p = 0.007 for COPD; r = 0.404, p < 0.001 for total subjects), adiponectin (r = 0.266, p = 0.004 for total subjects), and MMP-9 (r = 0.254, p = 0.03 for COPD). CONCLUSIONS: Our results suggest that circulating ANGPTL4 levels are up-regulated in COPD patients, and have correlations with pulmonary function and systematic inflammation in COPD, which provides a novel idea to further dig the pathogenic mechanisms of COPD, and justifies more studies to determine how ANGPTL4 contributes to COPD. PMID- 26813453 TI - Update on the treatment of androgenetic alopecia. AB - OBJECTIVE: Androgenetic alopecia is the most common type of hair loss, affecting women (50% of menopausal women and a large number of women of childbearing age) as well as males (over 70% of adult men). Since the condition is of an evolutionary nature, it is important to intervene early in order to prevent the progression of the clinical picture. It is equally important to identify all the factors that may hinder the effectiveness of the therapy. MATERIALS AND METHODS: A literature search was conducted using, as electronic bibliographic database, Medline and the Cochrane library from 1995 until present. RESULTS: Patients who make use of certain supplements can be less responsive to medical treatments. CONCLUSIONS: The therapeutic approach to the patient with androgenetic alopecia should be global as the effectiveness of valid therapies may be affected by the patient overlooking the information received from the specialist. PMID- 26813454 TI - Correlation between depression and burden observed in informal caregivers of people suffering from dementia with time spent on caregiving and dementia severity. AB - OBJECTIVE: The aim of the study is to compare data on the examined population of informal caregivers of people suffering from dementia with previous studies, as well as to assess the correlation between (i) depression determined on the basis of the Center for Epidemiologic Studies Depression Scale and (ii) caregiver burden measured by means of the Zarit Caregiver Burden Scale and some chosen parameters, such as total time devoted to caregiving, time of caregiving in hours per week and level of dementia severity measured by Global Deterioration Scale. PATIENTS AND METHODS: 41 informal caregivers of people suffering from dementia from different backgrounds were evaluated using the Zarit Caregiver Burden Scale and the Center for Epidemiologic Studies Depression Scale. Demographic data about the time devoted to caregiving and the number of hours spend on caregiving weekly were gathered. The type of dementia and its stage were registered using the Global Deterioration Scale (GDS). With the aid of the Statistica StatSoft program, mutual correlations between the parameters were measured. The study was conducted within the framework of AAL UnderstAID--a platform that supports and helps to understand and assist caregivers in the care of a relative with dementia. The international project is co-founded by the Joint Programme Ambient Assisted Living (Grant code: ESR-aal 2012 5 107). RESULTS: No significant correlations between the level of depression severity evaluated in caregivers and the total time of taking care of a demented person or time of caregiving in hours per week were observed. Similarly, no significant correlation between depression severity level and dementia severity level measured on the GDS scale were noted. There was also no significant correlation between Zarit Caregiver Burden Scale scores and the above-mentioned parameters. CONCLUSIONS: The level of depression among caregivers do not depend on socio-demographic factors. PMID- 26813456 TI - Correlation between intensity modulated radiotherapy and bone marrow suppression in breast cancer. AB - OBJECTIVE: To study the correlation factors of bone marrow suppression in breast cancer radiotherapy and find out the method to guide the target area, dose limitation for breast cancer to reduce the risk of bone marrow suppression. PATIENTS AND METHODS: 72 cases of breast cancer patients were collected through retrospective, clinical control study. For patients with Grade 0-3, bone marrow suppression in the course of radiotherapy, the dose-volume parameters (V5, V10, V20, V30, V50, D20, D40, D60, D80, D100, Min, Max, Dmean) of the chest and rib of each patient were collected and analyzed from multiple points including tumor stage, age, lesion location, surgical approach, chemotherapy regimen and the number of cycles, bone dose-volume parameters. RESULTS: The relative parameters of the rib in the middle and severe bone marrow suppression group were significantly higher than those in the mild bone marrow depression group and the p values of V5, V10, V20, V30, Dmean, D40, D60, D80, D100 were less than 0.05. The difference of V50 in the two groups was statistically significant (p <0.05). For chemotherapy regimens containing doxorubicin, epirubicin, cyclophosphamide, the differences between bone marrow suppression group and non-bone marrow suppression were statistically significant (p =0.002). CONCLUSIONS: The dose volume parameters of the rib radiation is one of the main factors causing the suppression of bone marrow in radiotherapy, and the volume of the 50Gy irradiation is also a contribution to the bone marrow. For patients accepted chemotherapy with doxorubicin, epirubicin, cyclophosphamide before radiotherapy, bone marrow suppression is more likely to occur during radiotherapy. After radical mastectomy or the volume of thoracic rib is increased because of the small breast, the occurrence of bone marrow suppression is increased. The effects of radiation on the bone marrow suppression were small, while its effect on the ribs was more evident, especially on the ribs V20 and Dmean and the difference was statically significant. PMID- 26813455 TI - Sorafenib in combination with transarterial chemoembolization for hepatocellular carcinoma: a meta-analysis. AB - OBJECTIVE: This meta-analysis aimed to analyze the efficacy of sorafenib in combination with transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Electronic data bases were searched for studies (1) enrolled HCC patients undergoing TACE; (2) with sorafenib therapy and control arm of no sorafenib therapy were included for meta-analysis and meta regression; (3) studies without control arm were included for data review and (4) had time to progression (TTP) and overall survival (OS) or relative outcome of HCC as the endpoint. Meta-analysis and meta-regression were performed according to Cochrane guidelines. RESULTS: Five studies (3 randomized trials, 1 cohort study and 1 prospective non- randomized controlled trial, totally 899 patients) were eligible for meta-analysis. The hazard ratio (HR) for TTP was 0.75 (95% CI: 0.48-1.03, p = 0.003) with significant heterogeneity (I2 = 82.7%) and for OS was 0.76 (95% CI: 0.47-1.05, p = 0.147) with slight heterogeneity (I2 = 47.9%). However, no covariate was found as independent predictor for better treatment efficacy. Hand-foot skin reaction, alopecia, rash/desquamation, diarrhea, hypertension, fatigue, anorexia, nausea and vomiting were common adverse events. CONCLUSIONS: TACE combined with sorafenib has potential efficacy for HCC. PMID- 26813457 TI - Clinical significance of sCIP2A levels in breast cancer. AB - OBJECTIVE: It has previously found that human oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) was overexpressed in breast cancer, and was positively correlated with lymph node metastasis of the patients. This study aimed to investigate the association between serum CIP2A and prognosis of breast cancer. Then, we investigated whether CIP2A could be as a therapeutic target in breast cancer treatment. PATIENTS AND METHODS: Preoperative CIP2A levels of 240 patients with breast cancer and 480 cases of controls were measured by ELISA method. The association of CIP2A levels with clinicopathological outcomes was investigated by univariate and multivariate analyses. The effect of CIP2A on breast cancer MDA-MB-231 cells was evaluated by CIP2A siRNA-mediated depletion of the CIP2A protein followed by an analysis of cell proliferation, invasion, colony growth, and xenograft growth and metastasis. RESULTS: The serum CIP2A levels in patients with breast cancer were (79.0 +/- 74.2) ng/mL, which was significantly higher than that in those controls (25.6 +/- 21.4) ng/mL for male and (24.8 +/- 20.6) ng/mL for female control. Higher preoperative CIP2A levels were significantly associated with the American Joint Committee on Cancer (AJCC) stage, histological grade and lymph node metastasis. Patients with elevated CIP2A levels showed worse survival. In multivariate analysis, elevated preoperative CIP2A levels were independent prognostic factors. Patients with high CIP2A levels had significantly shorter overall survival (OS) and disease-free survival (DFS) times. Knockdown of CIP2A by stable CIP2A siRNA transfection inhibited MDA-MB-231 cell proliferation, invasion, colony growth in vitro, and xenograft growth and metastasis in vivo. CONCLUSIONS: Our results suggest that serum CIP2A is significantly higher in patients with breast cancer, which is a potential biomarker to make a distinction between breast cancer patients and healthy controls. Higher serum CIP2A levels positively associated with the aggressive phenotype of breast cancer, and forecasts poor prognosis for patients with breast cancer. Knockdown of CIP2A may be a novel target for prevention and treatment of breast cancer. PMID- 26813458 TI - MiR-205 suppresses autophagy and enhances radiosensitivity of prostate cancer cells by targeting TP53INP1. AB - OBJECTIVE: This study aimed to investigate the role of miR-205 in radiosensitivity and autophagy of prostate cancer cells and to explore its regulative effect on TP53INP1. MATERIALS AND METHODS: MiR-205 expression was compared in three prostate cancer cell lines (DU145, PC-3 and LNCaP) and one normal human prostate epithelial cell line (RWPE-1). The effect of irradiation induced autophagy on radiosensitivity of the cancer cells and the effect of miR 205 on irradiation-induced autophagy were explored. The regulative effect of miR 205 on TP53INP1 and the function of this axis was further studied. RESULTS: Ectopic expression of miR-205 substantially reduced the survival fraction of both DU145 and LNCaP cells to irradiation and inhibited irradiation-induced autophagy. Irradiation-induced autophagy acted as a protective mechanism in prostate cancer cells. TP53INP1 is a direct functional target of miR-205 in irradiation-induced autophagy and radiosensitivity regulation. CONCLUSIONS: The miR-205/TP53INP1 mediated autophagy pathway might be an important molecular mechanism regulating radiosensitivity of prostate cancer cells and represents a potential therapeutic target for prostate cancer. PMID- 26813459 TI - Hypoxia induced upregulation of miR-301a/b contributes to increased cell autophagy and viability of prostate cancer cells by targeting NDRG2. AB - OBJECTIVE: Previous studies reported that NDRG2 might be a tumor suppressor of prostate cancer. In this study, we investigated the hypoxia-induced expression change of miR-301a/b in prostate cancer cells and explored its regulation on NDRG2 in autophagy and viability of prostate cancer cells. MATERIALS AND METHODS: MiR-301a/b expression in hypoxia and normoxia cultured prostate cancer cells was measured. Its regulation on autophagy was measured by quantifying expression change of LC3B and p62. The direct binding between miR-301a/b and 3'UTR of NDRG2 was verified using dual luciferase, qRT-PCR and Western blot assay. The influence of miR-301a/b-NDRG2 axis on autophagy, viability and apoptosis of prostate cancer cells was further investigated. RESULTS: Hypoxia induced a significant upregulation of miR-301a/b in prostate cancer cells. Enhanced miR-301a/b expression significantly weakened autophagy of prostate cancer cells. Both miR 301a and miR-301b could directly target 3'UTR of NDRG2 and decrease its expression. Decreased NDRG2 expression directly resulted in increased autophagy and cell viability and reduced cell apoptosis. CONCLUSIONS: Taken together, we demonstrated that miR-301a/b-NDRG2 might be an important axis modulating autophagy and viability of prostate cancer cells under hypoxia. PMID- 26813460 TI - The MTHFR C677T polymorphism is associated with mitral valve rheumatic heart disease. AB - OBJECTIVE: Rheumatic heart disease (RHD) is a serious complication of rheumatic fever (RF). Plasma homocysteine (Hcy) levels are increased in RHD patients. MTHFR catalyzes the irreversible conversion of 5,10-methylenetetrahydrofolate to 5 methyltetrahydrofolate and plays a vital role in Hcy metabolism. We hypothesize that the MTHFR C677T polymorphism is associated with a risk of RHD. PATIENTS AND METHODS: Eighty-six patients with RHD and 130 matched controls without a history of RHD were eligible for the study. The diagnosis of RHD was made according to modified Jones' criteria and echocardiography. Using echocardiography, RHD patients were further divided into mitral valve lesion (MVL) and combined valve lesion (CVL) groups. MTHFR C677T polymorphisms were genotyped by DNA sequencing. The chi-squared test was used to evaluate differences in genotypes. RESULTS: Control genotypes were in Hardy-Weinberg equilibrium. The C677T homozygous genotype (OR = 4.09; 95% CIs 1.16-14.44; p = 0.020) and recessive model (TT vs. CC+CT; OR = 4.05; 95% CIs 1.17-14.04; p = 0.019) were significantly associated with MVL RHD. CONCLUSIONS: This is the first study to investigate the association between the MTHFR C677T polymorphism and risk of RHD. The MTHFR C677T polymorphism is associated with RHD in patients with MVLs, perhaps via an Hcy mediated cytokine effect. PMID- 26813461 TI - Study on the expression of VEGF and HIF-1alpha in infarct area of rats with AMI. AB - OBJECTIVE: To investigate the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1alpha (HIF-1alpha) in infarct area of rats with acute myocardial infarction (AMI). MATERIALS AND METHODS: A total of 36 healthy male Wistar rats weighing 180 g-220 g were included in our study and were randomly divided into two groups of 6 rats each: sham operation group and experiment group. In sham operation group, surgery was performed by opening chest without ligation of arteria coronaria while, in the experiment group, surgery was performed to produce AMI model. Animals were sacrificed immediately after the operation on day 7 and day 14, respectively. The serum troponin, myocardial infarct area, microvessel density in infarct area, VEGF and HIF-1alpha expression were analyzed. RESULTS: Differences in the serum troponin level, myocardial infarct area, microvessel density in infarct area, VEGF and HIF-1 expression level at different time points in sham and experiment groups had statistical significance (p < 0.05). On day 7, the serum troponin, myocardial infarct area, microvessel density in infarct area, VEGF and HIF-1 expression level were the highest and the level was second highest on day 14 while the levels were lowest immediately after the operation. The expression levels of VEGF and HIF-1alpha were positively related with the increasing density of microvessel in infarct area (p < 0.05). CONCLUSIONS: The expression of VEGF and HIF-1alpha might be involved with myocardial remodeling and angiogenesis. PMID- 26813462 TI - Does the imbalance between agonistic and antagonistic IL-1 play a role in progression of febrile convulsions? AB - OBJECTIVE: Inflammation may play an important role in the etiopathology of febrile convulsions (FC). IL-1beta is an important mediator of inflammation and fever is also important information of FCs. It is suggested that there may be a relationship between polymorphisms of IL-1beta and FC. The aim of the present study is to investigate the polymorphic situation of promoter region of IL-1beta in two sites (-31 and -511) and assess the IL-1 RA VNTR polymorphisms in FC patients in comparison with healthy control groups. MATERIALS AND METHODS: Fifty FC patients and 50 healthy controls (HC) were included in the study. DNA extraction was performed by QIAamp DNA Mini Kit from peripheral blood lymphocytes of all subjects. IL-1beta promoter polymorphisms were analyzed by PCR-RFLP, IL-1 RA VNTR polymorphisms were analyzed by PCR-agarose gel electrophoresis. RESULTS: Genotype distribution of IL-1beta promoter region in position -31 was statistically different between FC patients and control groups. Allele I and allele II of IL-1 RA distribution were also statistically different in FC patients and healthy controls. CONCLUSIONS: We have found a significant association between IL-1 RA allele distribution and FC and a poor correlation of T/C substitution at the -31 position of IL-1beta promoter in FC. Further studies are needed to investigate the gene expression levels and polymorphic situation in same samples. PMID- 26813463 TI - The influence of continuous glucose monitoring of high-risk neonate on guiding perinatal complications and one-year follow-up results. AB - OBJECTIVE: To investigate the value of micro blood glucose monitoring of high risk neonate on guiding perinatal complications and one-year follow-up results. PATIENTS AND METHODS: A total of 268 cases that were diagnosed as high-risk neonates by our Obstetrics Department from June 2010 to June 2014 were enrolled. After measuring their micro blood glucose instantly, 6h, 12h, 24h, 1d, 2d and 3d after delivery, divided them into two groups: hypoglycemic group (n = 54) and normal group (n = 214). And then the differences of perinatal complications and their one-year follow-up results were compared. RESULTS: The occurrence of perinatal complications in hypoglycemic group was significantly higher than that in normal group (p < 0.05); the faster the hypoglycemia occurred, the longer the duration was, and the severer the complications were. Hypoglycemia often occurred prior to the complications. The mental development index (MDI) and the physical development index (PDI) of hypoglycemic group were significantly lower than those in the normal group and differences were statistically significant (p < 0.05). CONCLUSIONS: Continuous blood glucose monitoring of high-risk neonate was of great significance in guiding perinatal complications at one-year follow-up. PMID- 26813464 TI - Scolicidal effect of Allium sativum flowers on hydatid cyst protoscolices. AB - he s OBJECTIVE: Because there is no effective and safe drug therapy for hydatid cyst, finding of some new agents especially from herbal origin with a desired scolicidal effect attracts great attention for treatment and pre-surgical use to prevent the hydatid cyst recurrence. In this study, the scolicidal effect of ultrasonic methanol extract of Garlic (Allium sativum) flower is investigated. MATERIALS AND METHODS: Protoscolices were collected aseptically from sheep livers containing hydatid cyst and were exposed to different concentrations of extract for various exposure times. The viability of protoscolices was confirmed by 0.1% Eosin staining. RESULTS: The scolicidal activity of extract at a concentration of 50 mg ml-1 was 59, 76, 81 and 86% after 10, 30, 60, and 180 min of exposure respectively. The scolicidal effect at 100 mg ml-1 was 67, 78, 85 and 98% after various exposure times, respectively. The results of this study showed that the ultrasonic extract has high scolicidal activity and might be used as a natural scolicidal agent. CONCLUSIONS: Garlic flower extracts is a potent protoscolicid and might be used in hydatid cyst treatment and pre-surgery to prevent secondary cyst recurrence. PMID- 26813465 TI - Mechanisms of propofol attenuation of ketamine-induced neonatal brain injury. AB - OBJECTIVE: We studied the mechanisms of protective effects of propofol on ketamine-induced damage to neonatal cognitive function. MATERIALS AND METHODS: We utilized a rat model of ketamine anaesthesia. Eighty neonatal rats (7 days after birth) were divided into four groups: normal saline group, ketamine group, and low- and high-dose propofol combined with ketamine groups. Six hours after anaesthesia, we obtained hippocampal tissue, and quantified apoptotic index and total protein concentration, and assessed global proteomics changes induced by two tested drugs. The latter changes were documented by two-dimensional electrophoresis and matrix-assisted laser desorption/ ionization time of flight mass spectrometry. To evaluate cognitive functions, water maze test was applied after animals grew for 21 days. We further repeated proteomics studies at 21 days post-anaesthesia. RESULTS: Ketamine markedly up-regulated apoptotic index and decreased total protein concentration. Propofol dose-dependently reverted these adverse changes. Six hours post-anaesthesia, combined propofol and ketamine administration up-regulated the following proteins in the hippocampus: PD1A3, NDUFB10, HSPA8, ATP5JD, and PSMA1. Furthermore, the following proteins were down regulated: PPIA, PKM2, GFAP, NSE, PPIA, PKM2, and GFAP. After 21 days, animals treated with ketamine showed marked disturbances in cognitive function as demonstrated by increased time of the water maze test, whereas propofol diminished these changes. In addition, expression of proteins largely normalized in propofol-treated animals, with only two up-regulated proteins (FUBP3 and PRDX5) and three down-regulated proteins (GAPDH, AKR1A1, and VCP). CONCLUSIONS: Adverse effects of ketamine on cognitive function are reverted by propofol, also through beneficial effects on protein expression in the hippocampus. PMID- 26813466 TI - KLF2 and caveolin-1 as early indicators of acute lung injury induced by paraquat. AB - OBJECTIVE: The roles of Kruppel-like factors KLF2 and KLF4, and caveolin-1 (Cav 1) in acute lung injury (ALI) induced by paraquat (PQ) are insufficiently defined. Here we tested their expression in a rat model of ALI. MATERIALS AND METHODS: 80 Wistar rats were divided into control group and groups exposed to PQ for 6, 12, and 24 hours (20 animals/group). ALI was assessed by behavioural and pathological scores. In addition, we quantified the concentration of KLF2, KLF4, and Cav-1 in serum by ELISA, and expression of these proteins at the mRNA and protein level in lung tissue (respectively, qPCR and Western blot). RESULTS: Pathological scores were the highest at 12 hours after exposure to PQ. These changes correlated well with the kinetics of serum levels of KLF2, KLF4 and Cav 1. Thus, the lowest levels of the two former proteins were observed at 12 hours post-exposure, whereas Cav-1 levels peaked at this time point. In lung tissue, the kinetics of mRNA and protein expression of these proteins was different from the changes in the serum. Specifically, both KLF and Cav-1 mRNA expression changed significantly at 6 hours post-exposure to PQ, whereas KLF4 mRNA expression did not change significantly at any of the studied time points. Studies of at the protein level corroborated the observations of mRNA kinetics. CONCLUSIONS: We demonstrate here that lung tissue expression of KLF2 and Cav-1 is modulated early in the pathogenesis of ALI. These proteins could, therefore, serve as molecular markers for early diagnosis of this clinical condition. PMID- 26813467 TI - The effect of ginger (Zingiber officinalis) and artichoke (Cynara cardunculus) extract supplementation on gastric motility: a pilot randomized study in healthy volunteers. AB - OBJECTIVE: Prodigest(r) is the standardized combination of artichoke and ginger extracts. This combination was safe and effective in the treatment of functional dyspepsia. However, further evidence could be useful to shed new lights on the effect of Prodigest(r) on gastric motility. This pilot randomized study on healthy volunteers investigates the prokinetic activity of Prodigest(r). SUBJECTS AND METHODS: This was a randomized, cross-over study in healthy volunteers comparing Prodigest(r) versus placebo. Eleven healthy volunteers were enrolled. Each participant underwent two evaluations, at a 7-day interval. Ten minutes before the main meal, the baseline area of gastric volume was determined by ultrasonography. The subject was then given one Prodigest(r) or placebo capsule and, then consumed a standardized meal. One hour after the meal, the gastric volume was measured again. Two weeks after the second evaluation, three subjects repeated the above-mentioned procedures taking two capsules of Prodigest(r). RESULTS: The mean gastric area at baseline was 3.2 +/- 0.5 cm(2); after the meal, this figure was 8.4 +/- 0.7 cm(2) with Prodigest(r) and 11.0 +/- 1.5 cm2 with placebo (p<0.001). The after-meal gastric area was significantly smaller, with a 24% difference, following the combination of extracts, as compared with placebo (p<0.001). The effect of two capsules of Prodigest(r) seems to be more evident but due to the very small number of the patients sample further clinical data are necessary before confirming the dose-related effects. CONCLUSIONS: This pilot study shows that Prodigest(r), a standardized extract of ginger and artichoke, significantly promotes gastric emptying in healthy volunteers without being associated with notable adverse effects. PMID- 26813468 TI - Effects of spirulina consumption on body weight, blood pressure, and endothelial function in overweight hypertensive Caucasians: a double-blind, placebo controlled, randomized trial. AB - OBJECTIVE: Some studies have demonstrated the beneficial effects of Spirulina maxima (Arthrospira maxima) consumption on glycemic, lipid, and blood pressure parameters. The aim of this study was to investigate the effect of Spirulina maxima on body weight, blood pressure, and endothelial function. PATIENTS AND METHODS: In this randomized double-blind placebo-controlled trial, 40 patients with hypertension but lacking evidence of cardiovascular disease were enrolled to receive daily either 2.0 g Hawaiian spirulina or placebo for three months. Anthropometric parameters, systolic blood pressure (SBP), diastolic blood pressure (DBP), and stiffness index (SI) using digital plethysmography were measured before and after the intervention. RESULTS: After three months, there was no change in body mass index (BMI) or weight in either the spirulina or the placebo group. However, a significant reduction in SBP and SI was observed. The patients in the spirulina group showed significant reductions in BMI (26.9 +/- 3.1 vs. 25.0 +/- 2.7 kg/m(2), p = 0.0032), weight (75.5 +/- 11.8 vs. 70.5 +/- 10.3 kg, p < 0.001), SBP (149 +/- 7 vs. 143 +/- 9 mmHg, p = 0.0023), and SI (7.2 +/- 0.6 vs. 6.9 +/- 0.7 m/s, p < 0.001). The tested parameters did not change in the placebo group. CONCLUSIONS: This study demonstrates that three months of regular consumption of Spirulina maxima not only improves BMI and weight but also results in improvements in blood pressure and endothelial function spirulina in overweight patients with hypertension but lacking evidence of cardiovascular disease. PMID- 26813469 TI - Tramadol inhibits proliferation, migration and invasion via alpha2-adrenoceptor signaling in breast cancer cells. AB - OBJECTIVE: The aim of this study was to examine the function of tramadol on cell proliferation, migration and invasion in breast cancer cells in vitro, and to evaluate the effect of tramadol in vivo. Further, we explore the mechanism accounting for the role of tramadol on breast cancer cells. MATERIALS AND METHODS: Cell proliferation was detected by the methyl thiazolyl tetrazolium (MTT) assay. Wound healing assay and transwell assay was applied to quantify the migration and invasion ability of MDA-MB-231 cells. The expression of endogenous alpha2-adrenoceptor and ERK was measured by Western blotting. RESULTS: Tramadol at a clinical dose of up to 2 MUM significantly inhibited the proliferation, migration and invasion in a time-dependent manner from day 0 to 28 in vitro. Moreover, tramadol suppressed the growth of xenotransplant tumor in vivo markedly. Furthermore, the protein levels of alpha2-adrenoceptor and phosphorylated ERK were decreased by tramadol, whereas the expression of total ERK remained unchanged. In addition, downregulation of alpha2-adrenoceptor by yohimbine could mimic the effect of tramadol treatment. CONCLUSIONS: Collectively, we demonstrated that tramadol could inhibit proliferation, migration and invasion of breast cancers via inactivating alpha2-adrenoceptor signaling pathway. Our data provide the experimental fundamental for further investigation of the anti-cancer effect of tramadol in breast cancer cells. PMID- 26813470 TI - The influence of the time-of-day administration of sunitinib on the penetration through the blood-brain and blood-aqueous humour barriers in rabbits. AB - OBJECTIVE: Sunitinib is a multiple tyrosine kinase inhibitor (TKI) that exerts anti-tumor and antiangiogenic activity. It is used for the treatment of metastatic gastrointestinal stromal tumours, renal cell carcinoma and pancreatic neuroendocrine tumours. A few studies confirm the anti-tumour activity of sunitinib in brain tumours and uveal melanoma, as well as its efficacy in the reduction of brain metastases of some primary cancers. Therefore, the penetration of sunitinib through the blood-brain barrier (BBB) and blood-aqueous humour barrier (BAB) is an issue of growing interest. The aim of the study was to investigate the influence of the time-of-day administration on the penetration of sunitinib into the cerebrospinal fluid (CSF) and aqueous humour (AH). MATERIALS AND METHODS: The rabbits were divided into two groups: I (control group)- receiving sunitinib at 8 a.m., and II--receiving sunitinib at 8 p.m. Sunitinib was administered p.o. at a single dose of 25 mg. The concentrations of sunitinib and its active metabolite (SU12662) in the plasma, CSF, AH were measured with the validated HPLC-UV method. RESULTS: The plasma AUC0-t for sunitinib in group I was 2051.8 ng * h/mL, whereas in group II it was 3069.3 ng * h/mL. The aqueous humour AUC0-t for sunitinib in thr groups were 43.2 and 76.3 ng * h/mL, respectively. The cerebrospinal AUC0-t for sunitinib in groups I and II were 55.5 and 66.3 ng * h/mL, respectively. CONCLUSIONS: After the evening administration (8 p.m.) the exposure to sunitinib in the rabbits' plasma, AH and CSF was higher than after the morning administration (8 a.m.), but the degree of sunitinib penetration through the BAB and BBB was very low (< 5%) and comparable in both groups. PMID- 26813471 TI - Clinical study of double dose of valsartan combined with tacrolimus in treatment of diabetic nephropathy. AB - OBJECTIVE: To investigate the clinical effect of double dose of valsartan combined with tacrolimus in the treatment of diabetic nephropathy (DN). PATIENTS AND METHODS: HA total of 86 cases diagnosed with DN were selected from October 2013 to October 2014 in Zaozhuang Municipal Hospital, China. The study was approved by our hospital Ethics Committee and written consent was obtained from patients and their family members. Patients were randomly divided into three groups according to the sequence of admission, group A (conventional dose of valsartan group, n = 28 cases), group B (double dose of valsartan group, n = 29 cases) and group C (double dose of valsartan combined with tacrolimus group, n = 29). Clinical effects were compared by analyzing the renal function tests after 8 weeks. RESULTS: 24h urine protein, serum creatinine level of patients in group B and group C were significantly lower than that of group A. Those in group C was much lower. The glomerular filtration rates were significantly higher for group B and C than that of group A, and those in group C were much higher. The difference is statistically significant (p < 0.05). High-sensitivity C-reactive protein (hs CRP) and adiponectin levels of patients in group B and C of were significantly lower than that of group A and those in group C were much lower. The difference is statistically significant (p < 0.05). The high mobility group protein 1 (HMGB1) and renal tubular and interstitial damage index (TDI) of patients in B and C groups were significantly lower than those in the A group, and those in C group were significantly lower. The difference was statistically significant p < 0.05). The clinical effective rates of patients in group B and C were significantly higher than that in group A, and those of group C were much higher. The difference is statistically significant (p < 0.05). The recurrence rates of patients in group B and group C were significantly lower than those of group A and those in group C were much lower. The difference is statistically significant (p < 0.05). Patients in three groups showed no obvious drug complications. CONCLUSIONS: Double dose of valsartan combined with tacrolimus treatment of DN patients can improve clinical symptoms, reducing inflammation, inhibiting or even reversing the interstitial fibrosis, which will improve the curative effect and reduce the recurrence, as to provide a new theoretical basis for the clinical treatment of the disease. PMID- 26813472 TI - The effects of N-acetylcysteine on pulmonary functions in patients undergoing on pump coronary artery surgery: a double blind placebo controlled study. AB - OBJECTIVE: To investigate the effects of N-acetylcysteine (NAC) on pulmonary function tests and arterial blood gases in patients undergoing on-pump coronary artery surgery. PATIENTS AND METHODS: The effect of NAC was assessed within the scope of a prospective, single center, double-blind, placebo-controlled, parallel group study. Eighty-two patients undergoing coronary artery bypass grafting were randomized into two groups to receive either placebo (group 1, n = 40) or NAC (group 2, n=42). Both the NAC group and the placebo-receiving control group also included a COPD subgroup consisting of patients with an FEV1/FVC ratio of < 0.7 and an FEV1 value of 50-80%. Pulmonary function tests were performed preoperatively and on postoperative day 60. RESULTS: Both groups were similar with respect to age, gender, preoperative risk factors, ejection fraction (EF), mean cross-clamp time, ventilation time, intensive care unit (ICU) stay, atrial fibrillation (AF) and hospital stay (p > 0.05). Postoperative FVC and FEV1 values in group 1 and the postoperative FEV1, FEV1/FVC and FEF 25-75 values in group 2 were lower in comparison to their preoperative values. However, in both group 1 and 2, the decreases observed in these parameters were not statistically significant (p > 0.05). In the COPD subgroup of group 1, a postoperative decrease was observed in the FEV1 and FEF25-75 values, with the FEV1 decreasing by 4.55%, and the FEF25-75 decreasing by 4.2% (p < 0.05). In the COPD subgroup of group 2, no significant decrease was observed in the pulmonary function test values (p > 0.05). CONCLUSIONS: This study demonstrated that NAC administration in COPD patients undergoing on-pump coronary artery surgery resulted in the preservation of pulmonary functions. PMID- 26813473 TI - Trimetazidine hydrochloride as a new treatment for patients with peripheral vascular disease--an exploratory trial. AB - OBJECTIVE: To evaluate the therapeutic effect of trimetazidine hydrochloride in peripheral vascular disease patients who had Rutherford classification grade 2-3. PATIENTS AND METHODS: 72 patients with Rutherford classification grade 2-3 in peripheral vascular were recruited successfully, they were randomly assigned to control group (35 cases) and trimetazidine group (37 cases), patients in control group received conventional treatment and trimetazidine group received conventional treatment plus trimetazidine hydrochloride for 6 months. Their ankle brachial index (ABI), maximum walking distance, pain onset time and the maximum walking time were compared before and after the treatment. RESULTS: After 6 months' treatment, the ABI, maximum walking distance, pain onset time and the maximum walking time in two groups were both improved of when compared with before treatment (p < 0.05). The maximum walking distance, pain onset time and the maximum walking time in trimetazidine group were improved better than control (p < 0.05) while no evident improvement in ABI between the 2 groups (p > 0.05). CONCLUSIONS: Conventional therapy plus trimetazidine hydrochloride could significantly improve the clinical symptoms of patients with Rutherford classification Grade 2-3 in peripheral vascular. PMID- 26813474 TI - The importance of disclosing the conflict of interest (CoI) in the era of open access publishing. PMID- 26813475 TI - Hypothermic Machine Perfusion Reduced Inflammatory Reaction by Downregulating the Expression of Matrix Metalloproteinase 9 in a Reperfusion Model of Donation After Cardiac Death. AB - The exact mechanism by which hypothermic machine perfusion (HMP) improves the graft quality in kidney transplantation of donation after cardiac death (DCD) remains unclear. The aim of this study was to investigate the correlation between the expression of matrix metalloproteinase 9 (MMP-9) and inflammatory reaction in kidney ischemia-reperfusion (I/R) injury injury followed by cold storage (CS) or HMP model of DCD. New Zealand white rabbit kidneys were subjected to 35 min of warm ischemia and 1 h reperfusion, then preserved by either 1 h reperfusion (sham operated group), 4 h CS or 4 h HMP in vivo. Kidneys were reperfused 24 h followed by further analysis. No treatment was given to rabbits in the normal control group. The expression of MMP-9, nuclear factor-kappaB (NF-kappaB), and MMP-2 mRNA were detected by real-time PCR (RT-PCR). MMP-9 was located by immunohistochemistry and immunofluorescence methods. Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), myeloperoxidase (MPO), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured by kits for each groups. Compared with the CS group, the expression of MMP-9 and NF-kappaB mRNA were downregulated in HMP group (P < 0.05). In contrast, expression of MMP-2 mRNA had no statistical significance between CS group and HMP group (P > 0.05). In normal control and sham-operated groups, a low level of MMP-9 expression was detected in glomeruli. However, positive signals of MMP-9 were mostly located in the tubulointerstitium and the vascular wall of CS and HMP groups. Expression of TNF-alpha, IL-6, MDA, and activity of MPO decreased while activity of SOD in the HMP group increased in contrast to the CS group (P < 0.05). In conclusion, inflammatory cytokines mediated MMP-9 expression through NF-kappaB band to MMP-9 promoter region, resulting in renal injury. Therefore, HMP reduced inflammatory reaction by downregulating the expression of MMP-9, which may be the mechanism of kidney protection in I/R injury. PMID- 26813476 TI - An fMRI Study of Responses to Sexual Stimuli as a Function of Gender and Sensation Seeking: A Preliminary Analysis. AB - Although sexual cues produce stronger neural activation in men than in women, mechanisms underlying this differential response are unclear. We examined the relationship of sensation seeking and the brain's response to sexual stimuli across gender in 27 subjects (14 men, M = 25.2 years, SD = 3.6, 85.2% Caucasian) who underwent functional magnetic resonance imaging (fMRI) while viewing sexual and nonsexual images. Whole-brain corrected significant clusters of regional activation were extracted and associated with gender, sensation seeking, and sexual behaviors. Men responded more to sexual than nonsexual images in the anterior cingulate/medial prefrontal cortex (ACC/mPFC), anterior insula/lateral orbitofrontal cortex, bilateral amygdala, and occipital regions. Sensation seeking related positively to ACC/mPFC (r = 0.65, p = 0.01) and left amygdala (r = 0.66, p = 0.01) response in men alone, with both of these correlations being significantly larger in men than in women (ps < 0.03). The relationship between brain responses and self-reported high-risk and low-risk sexual behaviors showed interesting, albeit nonsignificant, gender-specific trends. These findings suggest the relationship between sexual responsivity, sensation seeking, and sexual behavior is gender specific. This study indicates a need to identify the gender-specific mechanisms that underlie sexual responsivity and behaviors. In addition, it demonstrates that the nature of stimuli used to induce positive mood in imaging and other studies should be carefully considered. PMID- 26813477 TI - Clinical outcome of epidermal growth factor receptor-tyrosine kinase inhibitors therapy for patients with overlapping kirsten rat sarcoma 2 viral oncogene homolog and epidermal growth factor receptor gene mutations. AB - BACKGROUND: Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) is the second most common mutated gene following epidermal growth factor receptor (EGFR) mutation in Chinese lung adenocarcinoma (LADC) patients. Investigating the clinical characteristics and outcomes of patients with co-existing KRAS and EGFR mutations can provide significant information for suitable therapies. METHODS: We retrospectively investigated 2106 LADC patients who had undergone EGFR and KRAS mutation tests at the Peking University Cancer Hospital. Only advanced LADC patients who carried KRAS and/or EGFR mutations, received EGFR-tyrosine kinase inhibitors (TKIs) and/or chemotherapy, and had completed follow-up analysis were analyzed further. KRAS and EGFR mutations were tested by denaturing high performance liquid chromatography. RESULTS: A KRAS mutation was detected in 123 out of 2106 LADC patients (5.8%) and 38 (1.8%) had a concurrent EGFR mutation. Seventy-two of 123 patients were advanced cases, which were divided into two sub groups according to EGFR mutation status: overlapping KRAS and EGFR mutations (n = 24) and KRAS mutation alone (n = 48). Clinical characteristics of the two subgroups were similar. A greater ratio of patients with double mutations received EGFR-TKIs compared to KRAS mutation alone (75% vs. 43.8%, P = 0.012), and obtained a better objective response rate (38.9% vs. 9.5%, P = 0.027) and longer progression-free survival (8.0 vs. 1.5 months, P = 0.028) following EGFR TKIs therapy. However, these differences were not observed in patients treated with platinum-based chemotherapy. CONCLUSIONS: Overlapping KRAS and EGFR mutations occurred in 1.8% of Chinese LADC patients studied. The co-presence of EGFR mutations could predict a clinical benefit from EGFR-TKIs treatment for patients with KRAS mutations. PMID- 26813479 TI - The reconstructive urology work force: present and future. AB - Indirect measures that determine the number of reconstructive urologists in the US seem to indicate a general shortage in the number of these specially trained surgeons. This shortage may worsen in the future, as the US population continues to age and the number of urologists relative to the general population growth continues to fall. The lack of reconstructive urology expertise seems to drive an inappropriate number of urethrotomies performed in the US, most troubling in those with previous failed urethotomies in whom the subsequent urethrotomy failure rate approaches 100%. Recently increases in the number of fellowship training programs and an increased number of residency centers nationwide that graduate urologists with good basic knowledge of urethroplasty will partly ameliorate this shortage, but wide geographic regions remain without any urologic reconstruction experts. PMID- 26813478 TI - A comparison between robotic-assisted laparoscopic distal pancreatectomy versus laparoscopic distal pancreatectomy. AB - BACKGROUND: This study aims to compare the early perioperative outcomes of robotic-assisted laparoscopic distal pancreatectomy (RDP) versus laparoscopic distal pancreatectomy (LDP). METHODS: The clinicopathologic features of 45 consecutive patients who underwent minimally-invasive distal pancreatectomy from 2006 to 2015 were retrospectively reviewed. RESULTS: Thirty-nine patients who met our study criteria were included. Eight patients underwent RDP and 31 had LDP. There were 10 (25.6%) open conversions. Six (15.4%) patients had major (> grade 2) morbidities and there was no in-hospital mortality. There were 14 (35.9%) grade A and 9 (23.1%) grade B pancreatic fistulas. Comparison between RDP and LDP demonstrated no significant difference between the patients' baseline characteristics except there was increased frequency of spleen-preserving pancreatectomies (3 (37.5%) vs 25 (80.6%), P=0.016) and splenic-vessel preservation (5 (62.5%) vs 4 (12.9%), P=0.003) in RDP. Comparison between outcomes demonstrated that RDP was associated with a longer median operation time (452.5 (range, 300-685) vs 245 min (range, 85-430), P=0.001) and increased frequency of the procedure completed purely laparoscopically (8 (100%) vs 18 (58.1%), P=0.025). CONCLUSIONS: RDP can be safely adopted and is equivalent to LDP in most perioperative outcomes. It is also associated with a decreased frequency of the need for hand-assistance laparoscopic surgery or open conversion but needed a longer operation time. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26813480 TI - Distribution of hospital beds in Tehran Province based on Gini coefficient and Lorenz curve from 2010 to 2012. AB - INTRODUCTION: Fair distribution of hospital beds across various regions is a controversial subject. Resource allocation in health systems rarely has focused on those who need it most and, in addition, is often influenced by political interests. The study assesses the distribution of hospital beds in different regions in Tehran, Iran, during 2010-2012. METHODS: This cross-sectional study was conducted in all regions of Tehran (22 regions) during 2010 to 2012. All hospital beds in these regions are included in the study. Data regarding populations of each region were obtained from the Statistics Center of Iran. According to the data, the total number of beds (N.B) and population (P) in 2010 (N.B=19075, P= 7585000), 2011 (N.B=21632, P= 9860500), and 2012 (N.B=21808, P=12818650). The instrument was a form, including the name of the hospital, the district in which the hospital was located, the number of staffed beds, the name of each region, and its population. Data analysis was performed using DASP software version 2.3. RESULTS: The results demonstrate that the Gini coefficient of distributed beds in 22 regions of Tehran was 0.46 in all three years and specifically calculated 0.4666 in 2010, 0.4658 in 2011 and 0.4652 in 2012. The Gini coefficient of beds in 22 regions of Tehran is not fair in comparison with the population of each region during the years 2010 to 2012. CONCLUSION: The results demonstrate that the distribution of beds in regions in Tehran is not fair in relation to the population of each region-and some regions had no hospitals. Therefore, it is essential for policymakers to frequently monitor this issue and investigate the fair distribution of hospital beds. PMID- 26813481 TI - Attitudes and Beliefs of Nursing Students Toward Mental Disorder: The Significance of Direct Experience With Patients. AB - PURPOSE: The objective of this study was to analyze nursing students' beliefs and attitudes toward mental disorder before and after clinical placements. DESIGN AND METHODS: A cross-sectional design was chosen. One hundred ninety-four first- and third-year students in a three-year nursing degree course completed the Attribution Questionnaire AQ-27 regarding Mental Health, the Questionnaire of Beliefs, and a Socio-Demographic Questionnaire. FINDINGS: Significant differences were found between students who had experienced mental illness and those who had not. Differences were also found between students with friends who suffered from mental health problems and those who did not. PRACTICE IMPLICATIONS: These results emphasize the need for nursing students to have direct interaction with people with a mental illness. PMID- 26813482 TI - Psychotherapy in a Rapidly Changing World. PMID- 26813483 TI - Online CBT Is Effective in Overcoming Cultural and Language Barriers in Patients With Depression. AB - OBJECTIVE: The goal of this study was to evaluate the efficacy of weekly email in delivering online cognitive behavioral therapy (CBT) to treat mild to moderately depressed individuals. The effectiveness of the online CBT was measured following treatment and then again at a 6-month follow-up and was compared with outcomes in a waitlist control group. METHODS: Participants were recruited through announcements on psychology Web sites, Iranian organization Web sites, and weblogs and flyers. Ninety-three individuals who met inclusion criteria, including a score >18 on the Beck Depression Inventory (BDI), participated in the study, with 47 randomly assigned to the CBT group and 46 to the control group. The CBT group received 10 to 12 sessions of online CBT conducted by a psychiatrist and a psychiatry resident. Following completion of the CBT, a second BDI was sent to participants. Another BDI was then sent to participants 6 months after the completion of treatment. RESULTS: Email-based CBT significantly reduced BDI scores compared with results in a waitlist control group following 10 to 12 weeks of treatment and at 6-month follow-up. CONCLUSIONS: Email is a viable method for delivering CBT to individuals when face-to-face interaction is not possible. Limitations and future directions are discussed. PMID- 26813484 TI - A Flexible-Dose Study of Paliperidone ER in Patients With Nonacute Schizophrenia Previously Treated Unsuccessfully With Oral Olanzapine. AB - OBJECTIVE: The goal of this study was to explore the tolerability, safety, and treatment response of switching from oral olanzapine to paliperidone extended release (ER). METHODS: Adult patients with nonacute schizophrenia who had been treated unsuccessfully with oral olanzapine were switched to flexible doses of paliperidone ER (3 to 12 mg/d). The primary efficacy outcome was a >= 20% improvement in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to endpoint for patients who switched medications because of lack of efficacy with olanzapine and noninferiority versus previous olanzapine treatment (mean endpoint change in PANSS total scores vs. baseline of <= 5 points) for patients who switched for reasons other than lack of efficacy. Safety and tolerability were assessed by monitoring adverse events, extrapyramidal symptoms, and weight change. RESULTS: Of 396 patients, 65.2% were men, mean age was 40.0 +/ 12.0 years, and 75.5% had paranoid schizophrenia. Among the patients whose main reason for switching was lack of efficacy, an improvement in the PANSS total score of >= 20% occurred in 57.4% of patients. Noninferiority was confirmed for each subgroup of patients whose main reason for switching was something other than lack of efficacy. Paliperidone ER was generally well tolerated. Extrapyramidal symptoms as measured by total Extrapyramidal Symptom Rating Scale scores showed statistically significant and clinically relevant improvements at endpoint, the average weight decreased by 0.8 +/- 5.2 kg at endpoint, and a clinically relevant weight gain of >= 7% occurred in 8.0% of patients. CONCLUSION: Paliperidone ER flexibly-dosed over 6 months was well tolerated and associated with a meaningful clinical response in patients with nonacute schizophrenia who had previously been unsuccessfully treated with oral olanzapine. PMID- 26813485 TI - Comorbidity of ADHD and High-functioning Autism: A Pilot Study on the Utility of the Overflow Movements Measure. AB - OBJECTIVES: Children with attention-deficit/hyperactivity disorder (ADHD) and high-functioning autism (HFA) commonly show neurological soft signs (NSS) and impairment in executive functioning (EF). Many children with HFA may experience ADHD-like symptoms, and the 2 disorders may be comorbid. Evaluating NSS and EF in drug-naive subjects with ADHD, HFA, and ADHD+HFA compared with healthy children may be critical in understanding and differentiating the biological substrates and cognitive phenotypes associated with these disorders. The goal of this study was to evaluate possible differences among these groups in motor and EF and the effects of comorbidity. METHODS: Thirty-eight drug-naive patients (13 with ADHD, 13 with HFA, 12 with ADHD+HFA) and 13 healthy controls (HC) were evaluated on measures of planning, verbal working memory, and response inhibition. Evaluation of NSS involved 3 primary variables: overflow movements (OM), dysrhythmia, and speed of timed activities. RESULTS: The group with ADHD and the group with HFA both showed impairment on measures of planning, response inhibition, and verbal working memory compared with the HC group. Moreover, the group with ADHD showed a greater number of NSS compared with the HC group, whereas the group with HFA showed greater dysrhythmia and slowness compared with the HC group. The group with ADHD+HFA showed deficits of planning and response inhibition and a greater number of NSS compared with the HC group. The group with ADHD+HFA showed greater impairment of planning compared with the other clinical groups and greater dysrhythmia compared with the group with ADHD. CONCLUSION: According to our data, the OM measure revealed a gradient in which ADHD was at one extreme (more OM) and HFA at the other extreme (less OM), whereas ADHD+HFA showed a number of OM that fell in the middle between the numbers for the ADHD and HFA groups. PMID- 26813486 TI - Correlates of Adolescent-reported and Parent-reported Family Conflict Among Canadian Adolescents With Bipolar Disorder. AB - BACKGROUND: Family conflict exacerbates the course of bipolar disorder (BP) among adults. However, few studies have examined family conflict among adolescents with BP, and fewer have looked at adolescent-reported and parent-reported family conflict separately. METHODS: Subjects were 89 adolescents, aged 13 to 19 years, with a diagnosis of BP on the basis of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL). Subjects were divided into high-conflict and low-conflict groups using a median split on the Conflict Behavior Questionnaire (child report and parent report). The chi(2) analyses and independent samples t tests were performed for univariate analyses. Multivariable logistic regression analyses were performed on variables with P<0.2. RESULTS: Parent-reported and adolescent reported Conflict Behavior Questionnaire scores were significantly correlated (r=0.50, P<0.001). High parent-reported family conflict was positively associated with recent manic symptoms, externalizing comorbidities, and dimensional scores reflecting emotional dysregulation. High adolescent-reported family conflict was positively associated with recent manic symptoms and emotional dysregulation, and negatively associated with socioeconomic status and lifetime psychiatric hospitalization. Bipolar subtype was significantly associated with high versus low family conflict. LIMITATIONS: The limitations of this study included being a cross-sectional study, use of a medium-sized sample, and lack of a control group. CONCLUSIONS: Despite substantial agreement between adolescents and parents regarding the amount of family conflict, there were meaningful differences in the factors associated with adolescent-reported and parent-reported conflict. These findings demonstrate the importance of ascertaining family conflict from adolescents as well as from parents. Moreover, these findings can potentially inform family therapy, which is known to be effective for adolescents with BP. PMID- 26813487 TI - Determining Whether a Definitive Causal Relationship Exists Between Aripiprazole and Tardive Dyskinesia and/or Dystonia in Patients With Major Depressive Disorder, Part 2: Preclinical and Early Phase Human Proof of Concept Studies. AB - This series of columns has 3 main goals: (1) to explain class warnings as used by the United States Food and Drug Administration, (2) to increase awareness of movement disorders that may occur in patients treated with antipsychotic medications, and (3) to understand why clinicians should refrain from immediately assuming a diagnosis of tardive dyskinesia/dystonia (TD) in patients treated with antipsychotics. The first column in this series began with the case of a 76-year old man with major depressive disorder who developed orofacial dyskinesias while being treated with aripiprazole as an antidepressant augmentation strategy. It was alleged that a higher than intended dose of aripiprazole (ie, 20 mg/d for 2 wk followed by 10 mg/d for 4 wk instead of the intended dose of 2 mg/d) was the cause of the dyskinetic movements in this man, and the authors were asked to review the case and give their opinion. The principal basis for this theory of causation was the class warning about TD in the package insert for aripiprazole. The rationale for concluding aripiprazole caused TD in the 76-year-old man led to this series of columns about aripiprazole, its potential--if any--to cause TD, and the presence of a class warning about TD in its package insert. The central point is to illustrate why class warnings exist and their implications for practice. The first column in this series focused on the historical background, incidence, prevalence, risk factors, and clinical presentations of tardive and spontaneous dyskinesias and concluded with a discussion of diagnostic considerations explaining why clinicians should avoid making a diagnosis of TD until a thorough differential diagnosis has been considered. This second column in the series reviews the pharmacology of aripiprazole and the preclinical and phase I translational human studies that suggest aripiprazole should have a low to nonexistent risk of causing TD compared with other antipsychotics. The third column in the series will review the systematic clinical trial data and "real world" data on TD and the use of aripiprazole as adjunctive treatment with antidepressants for major depressive disorder to see whether these data support the conclusion of a low to nonexistent relationship between aripiprazole treatment and the development of TD. The fourth and final column in the series will consider the type of study that would need to be performed to avoid a specific class warning, focusing on the TD class warning as an example and discussing why such studies are rarely done. PMID- 26813489 TI - Effectiveness of a Unique Support Group for Physicians in a Physician Health Program. AB - State Physician Health Programs (PHPs) assess, support, and monitor physicians with mental, behavioral, medical, and substance abuse problems. Since their formation in the 1970s, PHPs have offered support groups following the 12-step model for recovery from substance use disorders (SUDs). However, few programs have developed support groups for physicians without SUDs. This study at the Massachusetts PHP (Physician Health Services Inc.) represents the first effort to survey physician attitudes concerning a unique support group that goes beyond classic addiction models. The group was initiated because of the observation that physicians with problems other than SUDs did not fit easily into the 12-step framework. It was hypothesized that such a group would be effective in helping participants control workplace stress, improve professional and personal relationships, and manage medical and psychiatric difficulties. With a response rate of 43% (85 respondents), the survey identified a strong overall impact of the Physician Health Services Inc. support group, identifying positive effects in all areas of personal and professional life: family and friends, wellness, professional relationships, and career. Respondents identified the role of the facilitator as particularly important, underscoring the facilitator's capacity to welcome participants, manage interactions, set limits, and maintain a supportive emotional tone. The implications for physician health extend from supporting a broader application of this model to using a skilled facilitator to manage groups intended to reduce the stress and burnout of present-day medical practice. The results encourage PHPs, hospitals, medical practices, and physician groups to consider implementing facilitated support groups as an additional tool for maintaining physician health. PMID- 26813488 TI - Hoarding Symptoms Respond to Treatment for Rapid Cycling Bipolar II Disorder. AB - Although some studies have reported a relationship between hoarding and bipolar disorder, we are unaware of any previous description of how they may interact with each other and how they should be managed appropriately. A 48-year-old male depressed patient with hoarding symptoms and obsessive-compulsive disorder (OCD) was diagnosed with bipolar II disorder after 2 hypomanic episodes. The patient was treated unsuccessfully with different high-dose serotonin reuptake inhibitors and atypical antipsychotics, maintaining a pattern of 6 to 8 discrete, but severe, depressive episodes each year, always in association with a drastic worsening of his OCD and hoarding symptoms. T.he patient did not improve until the dose of the serotonin reuptake inhibitor was decreased and a combination of lamotrigine and methylphenidate was initiated. On this treatment regimen, the patient did not show clinically significant levels of depression or hoarding or other OCD symptoms. This case suggests that, in some patients, (1) hoarding related cognitions and behaviors may be a part of bipolar depression, (2) the episodic nature of rapid cycling bipolar II disorder may protect against the development of severe clutter, and (3) treatment focusing on bipolar depression (eg, lamotrigine plus methylphenidate) may result in an improvement of hoarding symptoms when these are present in patients with rapid cycling bipolar II disorder. PMID- 26813490 TI - Linking Orders in Electronic Medical Records Can Improve the Frequency With Which Recommended Treatments Are Ordered as Illustrated in the Treatment of Alcohol Withdrawal. AB - OBJECTIVE: The purpose of this study was to collect objective data concerning the prescription of vitamin supplementation treatment in hospitalized patients at risk for alcohol withdrawal. METHODS: This study compared the total number of orders for folate, thiamine, and multivitamins with assessments ordered using the revised Clinical Institute Withdrawal Assessment of Alcohol (CIWA-Ar) during 2 congruent time periods in a hospital system before and after these orders were linked to determine the effectiveness of the link. Frequency counts of the order sets containing CIWA-Ar with and without doses of folate, thiamine, and multivitamins were extracted from the electronic medical record. One set of frequencies was collected between January 1, 2012, and June 15, 2012. The second set was collected between January 1, 2013, and June 15, 2013, after the intervention in which these orders were linked. Percentages were calculated from the frequency counts. RESULTS: Results of the study showed that before the intervention linking these orders, thiamine was ordered only 41 times, folate 42 times, and multivitamin 42 times, whereas CIWA-Ar was ordered 1228 times within the same time parameters (3.34%, 3.42%, and 3.42%, respectively), for a total average rate of 10.18%. After orders for thiamine, folate, and multivitamins were linked to the CIWA-Ar, the average rate of these vitamins being ordered with CIWA Ar reached 77.94%. CONCLUSION: This study found that linking CIWA-Ar and vitamin supplementation orders within the electronic medical record increases the likelihood of them being ordered together. We propose that this can be applied to other treatments that are commonly ordered together and that such orders should be linked to improve the standards of care for all patients. PMID- 26813491 TI - Highly Efficient Quantum Sieving in Porous Graphene-like Carbon Nitride for Light Isotopes Separation. AB - Light isotopes separation, such as (3)He/(4)He, H2/D2, H2/T2, etc., is crucial for various advanced technologies including isotope labeling, nuclear weapons, cryogenics and power generation. However, their nearly identical chemical properties made the separation challenging. The low productivity of the present isotopes separation approaches hinders the relevant applications. An efficient membrane with high performance for isotopes separation is quite appealing. Based on first-principles calculations, we theoretically demonstrated that highly efficient light isotopes separation, such as (3)He/(4)He, can be reached in a porous graphene-like carbon nitride material via quantum sieving effect. Under moderate tensile strain, the quantum sieving of the carbon nitride membrane can be effectively tuned in a continuous way, leading to a temperature window with high (3)He/(4)He selectivity and permeance acceptable for efficient isotopes harvest in industrial application. This mechanism also holds for separation of other light isotopes, such as H2/D2, H2/T2. Such tunable quantum sieving opens a promising avenue for light isotopes separation for industrial application. PMID- 26813492 TI - Photoelectrochemical water splitting using WO3 photoanodes: the substrate and temperature roles. AB - The influence of a substrate on the performance of WO3 photoanodes is assessed as a function of temperature. Two samples were studied: WO3 deposited on a FTO glass and anodized on a tungsten foil. Current-voltage curves and electrochemical impedance spectroscopy measurements were used to characterize these samples between 25 degrees C and 65 degrees C. The photocurrent density increased with temperature for both samples and the onset potential shifted to lower potentials. However, for WO3/FTO, a negative shift of the dark current onset was also observed. The intrinsic resistivity of this substrate limits the photocurrent plateau potential range. On the other hand, this behavior was not observed for WO3/metal. Therefore, the earlier dark current onset observed for WO3/FTO was assigned to the FTO layer. The optimal operating temperatures observed were 45 degrees C and 55 degrees C for WO3/FTO and WO3/metal, respectively. For higher temperatures, the bulk electron-hole recombination phenomenon greatly affects the overall performance of WO3 photoanodes. The stability behavior was then studied at these temperatures over 72 h. For WO3/FTO, a crystalline-to-amorphous phase transformation occurred during the stability test, which may justify the current decrease observed after the aging period. The WO3/metal remained stable, maintaining its morphology and good crystallinity. Interestingly, the preferential orientation of the aged crystals was shifted to the (-222) and (222) planes, suggesting that this was responsible for its better and more stable performance. These findings provide crucial information for allowing further developments on the preparation of WO3 photoanodes, envisaging their commercial application in PEC water splitting cells. PMID- 26813493 TI - An ecological model organism flies into the genomics era. AB - Despite the very rapid 'genomicization' of the field of Molecular Ecology in recent years, there have been relatively few annotated whole-genome assemblies of nonmodel organisms published. Instead, molecular ecologists have more frequently utilized next-generation sequencing technologies to develop genome-wide markers or to generate transcriptome data. Whole-genome assemblies are more expensive and require considerable computational resources and bioinformatic expertise. However, the availability of an annotated genome offers exciting opportunities to address fundamental questions in ecology and evolution that are difficult to address with moderate sets of markers or by transcriptome sequencing. Such questions include elucidating the roles of natural and sexual selection in shaping diversity, determining the roles of regulatory and protein-coding change in the evolution of traits, and determining the genomic architecture of sex specific trait variation. Arguably, these questions are most tractable--and most interesting--in well-characterized species for which there is already some knowledge of natural and sexual selection, and of the traits that are most likely to link to fitness. In this issue, Mueller et al. (2016) present the assembly and annotation of the genome of the blue tit (Cyanistes caeruleus), a model ecological species. In addition, by sequencing the transcriptome of male and female blue tits, the authors identify and annotate sex-biased gene expression and conclude that noncoding RNA genes are likely to play a significant role in sex-biased expression. By making their assembly and annotation publically available and accessible via a genome browser, Mueller et al. (2016) offer exciting possibilities for further research into the genomic basis of adaptation, and investigation of the roles of natural and sexual selection, in this well studied ecological model species. PMID- 26813494 TI - P-LOCI: a computer program for choosing the most efficient set of loci for parentage assignment. PMID- 26813495 TI - The dual function of PRMT1 in modulating epithelial-mesenchymal transition and cellular senescence in breast cancer cells through regulation of ZEB1. AB - Although the involvement of protein arginine methyltransferase 1 (PRMT1) in tumorigenesis has been reported, its roles in breast cancer progression and metastasis has not been elucidated. Here we identified PRMT1 as a key regulator of the epithelial-mesenchymal transition (EMT) in breast cancer. We showed that the EMT program induced by PRMT1 endowed the human mammary epithelial cells with cancer stem cell properties. Moreover, PRMT1 promoted the migratory and invasive behaviors in breast cancer cells. We also demonstrated that abrogation of PRMT1 expression in breast cancer cells abated metastasis in vivo in mouse model. In addition, knockdown of PRMT1 arrested cell growth in G1 tetraploidy and induced cellular senescence. Mechanistically, PRMT1 impacted EMT process and cellular senescence by mediating the asymmetric dimethylation of arginine 3 of histone H4 (H4R3me2as) at the ZEB1 promoter to activate its transcription, indicating the essential roles of this epigenetic control both in EMT and in senescence. Thus, we unraveled a dual function of PRMT1 in modulation of both EMT and senescence via regulating ZEB1. This finding points to the potent value of PRMT1 as a dual therapeutic target for preventing metastasis and for inhibiting cancer cell growth in malignant breast cancer patients. PMID- 26813497 TI - [Intracellular and extracellular functions of phosphorus compound in the body]. AB - Phosphorus, as a phosphate is a component of bone, cellular membrane, and also high-energy phosphate compounds, and nucleic acids. Also phosphate acts as a buffer to maintain the pH and is concerned with functional regulation of several proteins and intracellular signaling through the phosphorylation/dephosphorylation. Thus phosphorus plays a variety of important roles intracellular and extracellular component. A disorder of phosphate homeostasis results bone disorder and general metabolic dysfunction of all body tissues and organs. PMID- 26813498 TI - [Regulatory mechanism of circulating inorganic phosphate]. AB - Circulating level of phosphate is altered by age and diet, and is also controlled by several hormones such as parathyroid hormone(PTH), 1,25-dihydroxyvitamin D[1,25(OH)2D]and fibroblast growth factor 23(FGF23). The main function of PTH and 1,25(OH)2D is maintaining calcium homeostasis, while FGF23 plays a central role in phosphate metabolism. PTH suppresses phosphate reabsorption in the proximal tubules to increase the renal phosphate wasting, while 1,25(OH)2D facilitates the intestinal phosphate absorption. FGF23 increases the renal phosphate wasting and reduces the production of 1,25(OH)2D. Of note, these hormones mutually regulate one another. The production of FGF23 is also regulated by various local factors. The mechanism for sensing the phosphate availability still remains unknown, and further investigation is required. PMID- 26813496 TI - Rapid endothelial cytoskeletal reorganization enables early blood-brain barrier disruption and long-term ischaemic reperfusion brain injury. AB - The mechanism and long-term consequences of early blood-brain barrier (BBB) disruption after cerebral ischaemic/reperfusion (I/R) injury are poorly understood. Here we discover that I/R induces subtle BBB leakage within 30-60 min, likely independent of gelatinase B/MMP-9 activities. The early BBB disruption is caused by the activation of ROCK/MLC signalling, persistent actin polymerization and the disassembly of junctional proteins within microvascular endothelial cells (ECs). Furthermore, the EC alterations facilitate subsequent infiltration of peripheral immune cells, including MMP-9-producing neutrophils/macrophages, resulting in late-onset, irreversible BBB damage. Inactivation of actin depolymerizing factor (ADF) causes sustained actin polymerization in ECs, whereas EC-targeted overexpression of constitutively active mutant ADF reduces actin polymerization and junctional protein disassembly, attenuates both early- and late-onset BBB impairment, and improves long-term histological and neurological outcomes. Thus, we identify a previously unexplored role for early BBB disruption in stroke outcomes, whereby BBB rupture may be a cause rather than a consequence of parenchymal cell injury. PMID- 26813499 TI - [Pathogenesis of hypophosphatemia]. AB - Chronic hypophosphatemia is seriously involved in several disorders of musculoskeletal system. Symptoms of patients are usually non-specific, such as pain with or without muscle weakness on lower extremities and are often hard to be correctly diagnosed. It is clinically important for physicians to understand pathogenesis and clinical features of hypophosphatemia and its related diseases. PMID- 26813501 TI - [Diagnostic criteria for vitamin D-deficient rickets and hypocalcemia-]. AB - Vitamin D deficiency causes rickets or osteomalacia, which is associated with hypomineralization of bone and chondrocytes, and/or hypocalcemia. Accumulating evidence indicates increase in frequency of vitamin D deficiency due to insufficient intake of vitamin D and calcium and decrease in sunshine. It is necessary for clinician to diagnose vitamin D deficiency accurately and treat patients with vitamin D deficiency adequately. For the purpose, clinical guideline or expert opinion on vitamin D deficiency has been reported. PMID- 26813500 TI - [Pathogenesis and clinical condition of hyperphosphatemic diseases]. AB - Phosphorus is essential mineral to life, which has the multiple roles like postural maintenance or production of energy in the cells. Phosphate overload is harmful and compensatory mechanisms exist. Phosphate is abolished through kidneys and target organ of the compensatory mechanism is also kidneys. It is necessary to evaluate renal function and source of phosphate for estimating the cause of hyperphosphatemia. Acute hyperphosphatemia may cause severe acute kidney injury and avoidance of massive phosphate overload is needed. Chronic hyperphosphatemia have an impact on prognosis because the risk of cardiovascular event increases. Adequate restriction of phosphate intake and use of phosphate absorbent is needed for improvement of prognosis of patients with chronic kidney disease. PMID- 26813503 TI - [Inhitibion of FGF23 activities as a possible new treatment for patients with FGF23-related hypophosphatemic diseases]. AB - Excessive actions of fibroblast growth factor 23(FGF23)result in several kinds of hypophosphatemic rickets and osteomalacia. A combination of oral active vitamin D3 and phosphate is the current standard therapy for FGF23-related hypophosphatemia. However, these medications can lead to long-term complications, such as secondary hyperparathyroidism and renal impairment. Therefore, safer and more efficient therapy to correct excessive actions of FGF23 is needed. X-linked hypophosphatemic rickets(XLHR)is the most prevalent form of FGF23-related hypophosphatemia. The efficacy of anti-FGF23 antibody was confirmed in a Hyp mouse, a murine model of XLHR. A recent phase 1 double-blind, placebo-controlled study and the subsequent open-label phase 1/2 study in adults with XLHR showed the safety and the efficacy of human anti-FGF23 antibody, KRN23. KRN23 has a potential for effectively treating patients with XLHR and other types of FGF23 related hypophosphatemia as well. PMID- 26813502 TI - [Epidemiology of FGF23-related hypophosophatemic diseases]. AB - Through the studies of patients with hypophosphatemic rickets/osteomalacia, fibroblast growth factor 23(FGF23)has emerged as a humoral factor that reduces serum phosphate. Discovery of FGF23 as an essential regulator of phosphate homeostasis has markedly improved our understanding of phosphate homeostasis and hypophosphatemic or hyperphosphatemic disorders. A nationwide epidemiologic survey of FGF23-related hypophosphatemic diseases indicated that the patients showed FGF23 levels of above 30 pg/mL by intact assay in the presence of hypophosphatemia. The survey also showed that prevalence and biochemical data before and after treatment of the diseases. Novel therapeutic methods for these disorders may be developed by elucidation of the mechanism of action of FGF23. PMID- 26813504 TI - [Phosphate metabolism and iron deficiency]. AB - Autosomal dominant hypophosphatemic rickets(ADHR)is caused by gain-of-function mutations in FGF23 that prevent its proteolytic cleavage. Fibroblast growth factor 23(FGF23)is a hormone that inhibits renal phosphate reabsorption and 1,25 dihydroxyvitamin D biosynthesis. Low iron status plays a role in the pathophysiology of ADHR. Iron deficiency is an environmental trigger that stimulates FGF23 expression and hypophosphatemia in ADHR. It was reported that FGF23 elevation in patients with CKD, who are often iron deficient. In patients with nondialysis-dependent CKD, treatment with ferric citrate hydrate resulted in significant reductions in serum phosphate and FGF23. PMID- 26813505 TI - [Vitamin D insufficiency/deficiency:its clinical significance and treatment]. AB - Vitamin D insufficiency/deficiency, a medical condition in which vitamin D store is decreased, is the most frequent cause of decreased action of vitamin D. Severer form vitamin D deficiency can cause hypocalcemia and rickets/osteomalacia. Milder form vitamin D insufficiency also harms bone health via secondary hyperparathyroidism, the increase in fracture risk, and poor responses to anti-osteoporotic medications. Diagnosis can only be made by measuring serum 25(OH)D, which is not currently covered by the Japanese health insurance policy. In Japan, the guideline for the diagnosis vitamin D insufficiency/deficiency is in the process of drafting. According to the current provisional guideline draft that was made in public, vitamin D deficiency would be defined by serum 25(OH)D level less than 20 ng/mL whereas vitamin D insufficiency would refer to the state in which serum 25(OH)D level is between 20 and 30 ng/mL. PMID- 26813506 TI - [Treatment for CKD-MBD(Chronic Kidney Disease-Mineral and Bone Disorder)]. AB - CKD is a common disease that is estimated to develop one in eight persons in Japan. The CKD itself is highly risk factor on the cardiac/vascular mortality. In addition,a new concept has been proposed "CKD-MBD". CKD-MBD is composed of a combination of abnormal mineral metabolism, abnormal bone, and extra skeletal calcification with cardiovascular high mortality. Treatment for CKD-MBD is a wide ranging. We aim to decline cardiovascular event, fracture, and mortality rate of patients with CKD. The main therapeutic target for CKD-MBD becomes the phosphate control. Today, we can use of the VRDA, Calcimimetics and muti-phosphate binders as a lot of pharmacological intervention. PMID- 26813507 TI - [FGF23 related hypophosphatemic rickets:current therapy and unresolved issues]. AB - FGF23-related hypophosphatemic rickets is basically treated with active vitamin D and phosphorus. The treatment goals are to minimize bone deformity and improve adult height in children, and to relieve pain and decrease osteomalacia in adult. However, since they do not target the underlying molecular defect, bone deformity can worsen during growth and adult height is suboptimal restricted. Many adult patients suffer from enthesopathy leading to symptoms such as spinal cord compression and debilitating pain. At present, no treatment is effective in preventing or revenging this complication. The recently developed anti-FGF23 antibody may potentially be a more fundamental treatment. PMID- 26813508 TI - [Vitamin D dependency and its treatment]. AB - Vitamin D dependency is classified to vitamin D-dependent rickets type 1 which shows defective 1,25(OH)(2)D production, and vitamin D-dependent rickets type 2 which shows end-organ unresponsiveness to 1,25(OH)(2)D. Recent advance in the molecular analysis of these diseases revealed variety in the presentation and in the inheritance patterns. Molecular diagnosis would be preferable for adequate therapy especially in type 2. PMID- 26813509 TI - [Renal hypophosphatemia:pathophysiology and treatment]. AB - Serum level of phosphate is regulated by the kidney, especially proximal tubule. The transcellular transport of phosphate in the proximal tubule is mediated via Na dependent transporters, i.e., NPT2a and NPT2b at the luminal membrane, and unknown channel at the basolateral side. The transport of phosphate via NPT2a and NPT2b is further regulated by factors, such as PTH, FGF23, and 1,25(OH)(2)D. Several hereditary diseases that cause hypophoshatemia specically are known. In addition, dysfunction of proximal tubule may develop Fanconi syndrome, which also causes hypherphosphaturia. In this section, I describe the renal mechanisms of phosphate handling and the causes of hypophosphatemia along with its treatment. PMID- 26813510 TI - [NF-kappaB signaling pathways and the future perspectives of bone disease therapy using selective inhibitors of NF-kappaB]. AB - The transcriptional factor nuclear factor kappaB(NF-kappaB)regulates the expression of a wide variety of genes that are involved in immune and inflammatory responses, proliferation, and tumorigenesis. NF-kappaB consists of five members, such as p65(RelA), RelB, c-Rel, p50/p105(NF-kappaB1), and p52/p100(NF-kappaB2). There are two distinct NF-kappaB activation pathways, termed the classical and alternative NF-kappaB signaling pathways. Since mice lacking both p50 and p52 subunits developed typical osteopetrosis, due to total lack of osteoclasts, NF-kappaB is also important osteoclast differentiation. A selective NF-kappaB inhibitor blocked receptor activator of NF-kappaB ligand(RANKL)-induced osteoclastogenesis both in vitro and in vivo. Recent findings have shown that inactivation of NF-kappaB enhances osteoblast differentiation in vitro and bone formation in vivo. NF-kappaB is constitutively activated in many cancers including oral squamous cell carcinoma(OSCC), and is involved in the invasive characteristics of OSCC. A selective NF-kappaB inhibitor also prevented jaw bone destruction by OSCC by reduced osteoclast numbers in animal model. Thus the inhibition of NF-kappaB might useful for the treatment of bone diseases, such as arthritis, osteoporosis, periodontitis, and bone invasion by OSCC by inhibiting bone resorption and by stimulating bone formation. PMID- 26813511 TI - Effect of porosities of bilayered porous scaffolds on spontaneous osteochondral repair in cartilage tissue engineering. AB - Poly(lactide-co-glycolide)-bilayered scaffolds with the same porosity or different ones on the two layers were fabricated, and the porosity effect on in vivo repairing of the osteochondral defect was examined in a comparative way for the first time. The constructs of scaffolds and bone marrow-derived mesenchymal stem cells were implanted into pre-created osteochondral defects in the femoral condyle of New Zealand white rabbits. After 12 weeks, all experimental groups exhibited good cartilage repairing according to macroscopic appearance, cross section view, haematoxylin and eosin staining, toluidine blue staining, immunohistochemical staining and real-time polymerase chain reaction of characteristic genes. The group of 92% porosity in the cartilage layer and 77% porosity in the bone layer resulted in the best efficacy, which was understood by more biomechanical mimicking of the natural cartilage and subchondral bone. This study illustrates unambiguously that cartilage tissue engineering allows for a wide range of scaffold porosity, yet some porosity group is optimal. It is also revealed that the biomechanical matching with the natural composite tissue should be taken into consideration in the design of practical biomaterials, which is especially important for porosities of a multi-compartment scaffold concerning connected tissues. PMID- 26813513 TI - Frequency and characteristics of acne-related post-inflammatory hyperpigmentation. AB - In patients with darker skin types (Fitzpatrick phototypes III-VI), acne is often accompanied by post-inflammatory hyperpigmentation (PIH). Further, acne-related pigmentation can pose a greater concern for the patient than the acne lesions. There has been little formal study of this acne-related PIH. Recently, the Asian Acne Board - an international group of dermatologists with interest in acne research - made a preliminary evaluation of the frequency and characteristics of PIH in seven Asian countries. A total of 324 sequential acne subjects were evaluated for the presence of PIH. The majority (80.2%) of subjects had mild to moderate acne and there were more females than males (63.0% vs 37.0%). In this population of patients consulting a dermatologist for acne, 58.2% (188/324) had PIH. The results also showed that pigmentation problems are often long lasting: at least 1 year for more than half of subjects and 5 years or longer in 22.3%. In accordance with our clinical experience, patients reported that PIH is quite bothersome, often as bothersome or more so than the acne itself and sometimes more problematic. Excoriation was commonly reported by patients, and may represent a modifiable risk factor that could potentially be improved by patient education. PMID- 26813512 TI - Features of Computer-Based Decision Aids: Systematic Review, Thematic Synthesis, and Meta-Analyses. AB - BACKGROUND: Patient information and education, such as decision aids, are gradually moving toward online, computer-based environments. Considerable research has been conducted to guide content and presentation of decision aids. However, given the relatively new shift to computer-based support, little attention has been given to how multimedia and interactivity can improve upon paper-based decision aids. OBJECTIVE: The first objective of this review was to summarize published literature into a proposed classification of features that have been integrated into computer-based decision aids. Building on this classification, the second objective was to assess whether integration of specific features was associated with higher-quality decision making. METHODS: Relevant studies were located by searching MEDLINE, Embase, CINAHL, and CENTRAL databases. The review identified studies that evaluated computer-based decision aids for adults faced with preference-sensitive medical decisions and reported quality of decision-making outcomes. A thematic synthesis was conducted to develop the classification of features. Subsequently, meta-analyses were conducted based on standardized mean differences (SMD) from randomized controlled trials (RCTs) that reported knowledge or decisional conflict. Further subgroup analyses compared pooled SMDs for decision aids that incorporated a specific feature to other computer-based decision aids that did not incorporate the feature, to assess whether specific features improved quality of decision making. RESULTS: Of 3541 unique publications, 58 studies met the target criteria and were included in the thematic synthesis. The synthesis identified six features: content control, tailoring, patient narratives, explicit values clarification, feedback, and social support. A subset of 26 RCTs from the thematic synthesis was used to conduct the meta-analyses. As expected, computer-based decision aids performed better than usual care or alternative aids; however, some features performed better than others. Integration of content control improved quality of decision making (SMD 0.59 vs 0.23 for knowledge; SMD 0.39 vs 0.29 for decisional conflict). In contrast, tailoring reduced quality of decision making (SMD 0.40 vs 0.71 for knowledge; SMD 0.25 vs 0.52 for decisional conflict). Similarly, patient narratives also reduced quality of decision making (SMD 0.43 vs 0.65 for knowledge; SMD 0.17 vs 0.46 for decisional conflict). Results were varied for different types of explicit values clarification, feedback, and social support. CONCLUSIONS: Integration of media rich or interactive features into computer based decision aids can improve quality of preference-sensitive decision making. However, this is an emerging field with limited evidence to guide use. The systematic review and thematic synthesis identified features that have been integrated into available computer-based decision aids, in an effort to facilitate reporting of these features and to promote integration of such features into decision aids. The meta-analyses and associated subgroup analyses provide preliminary evidence to support integration of specific features into future decision aids. Further research can focus on clarifying independent contributions of specific features through experimental designs and refining the designs of features to improve effectiveness. PMID- 26813514 TI - The role of inhibitory dynamics in the loss and reemergence of macropodoid tooth traits. AB - The reversibility of phenotypic evolution is likely to be strongly influenced by the ability of underlying developmental systems to generate ancestral traits. However, few studies have quantitatively linked these developmental dynamics to traits that reevolve. In this study, we assess how changes in the inhibitory cascade, a developmental system that regulates relative tooth size in mammals, influenced the loss and reversals of the posthypocristid, a molar tooth crest, in the kangaroo superfamily Macropodoidea. We find that posthypocristid loss is linked with reduced levels of posterior molar inhibition, potentially driven by selection for lophodont, higher-crowned molar teeth. There is strong support for two posthypocristid reversals, each occurring after more than 15 million years of absence, in large-bodied species of Macropus, and two giant extinct species of short-faced sthenurine kangaroo (Procoptodon). We find that whereas primitive posthypocristid expression is linked to higher levels of posterior molar inhibition, reemergence is tied to a relative increase in third molar size associated with increasing body mass, producing molar phenotypes similar to those in mouse where the ectodysplasin pathway is upregulated. We argue that although shifts in the inhibitory cascade may enable reemergence, dietary ecology may limit the frequency of phylogenetic reversal. PMID- 26813516 TI - Metal-based bracken-like single-sided dye-sensitized solar cells with horizontal separation. AB - One of the drawbacks of typical dye-sensitized solar cells (DSCs) is their high cost and the high electrical resistance of the transparent conducting substrate. In conventional sandwich-type DSCs, only one of the FTO substrates can be replaced by a metal substrate. We investigated an all-metal-electrode single sided DSC in which interpenetrated bracken-like Cr electrodes were created using photolithography; mesoporous TiO2 and Pt films were deposited on the laterally separated electrodes. Thermal Pt deposition and electrodeposition methods were investigated and it was found that a cyclic electrodeposition method resulted in selective Pt deposition at room temperature with a higher device performance. Cu or ZnO sacrificial layers and TiO2 or TiO2/SiO2 porous layers were used for the spacer layer that keeps the Pt electrode away from the TiO2 mesoporous layer and the optimum results were obtained when a TiO2/SiO2 layer was used. The best device had a current density of 8.47 mA cm(-2), an open circuit voltage of 0.685 V and an efficiency of 2.44%. The results of open circuit voltage decay and electrochemical impedance spectrometry showed the formation of a high-resistivity blocking layer, which was attributed to the Cr oxide formed during thermal treatment. The efficiency may be improved further by developing low-temperature fabrication processes. PMID- 26813515 TI - Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case-Control Study. AB - Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group. PMID- 26813517 TI - Anxiety, stress, depression, and psychosocial functioning of Indian adolescents. AB - BACKGROUND: Lifetime prevalence of depression and anxiety increases from 1% of the population under age 12 years to ~17%-25% of the population by the end of adolescence. The greatest increase in new cases occurs between 15-18 years. Indian empirical studies have reported a prevalence of psychiatric morbidity in the range between 14.4% and 31.7%; thus, affecting psychosocial functioning. AIMS: The objectives of the current study were to (i) examine the psychometric properties of the DASS and SDQ on Indian adolescents, (ii) explore the role of socio- demographic variablesand (iii) examine if there was any difference between school going and school dropouts. METHODOLOGY: Data from 1812 students, aged 12 19 years was collected with mean age = 15.67 years (SD =1.41 years). The participants were administered a booklet containing demographic questionnaire and psychometric scales such as DASS-21 (Henry & Crawford, 2005; Lovibond & Lovibond, 1999) and Strengths and Difficulties Questionnaire (Goodman, 1997). STATISTICAL ANALYSIS: Structure validation, correlational analysis and multivariate analysis. RESULTS AND CONCLUSIONS: The results of validation indicated that English and Hindi version of 3 factor model of DASS and 2 factor model of SDQ was an acceptable model fit. It was noted that early adolescents were high on prosocial behaviour whereas late adolescents were high on difficulties score. Females were higher than males on prosocial behaviour. Adolescents residing in rural areas differed from their urban counterparts on prosocial behaviour and anxiety. Government school going adolescents differed from private school going adolescents on prosocial behaviour, stress and anxiety. Negative perception of relationship with family affected adolescents difficulties score, depression and stress. Similarly, negative perception of self-concept leads to higher difficulties score and lower prosocial behaviour score. The school going adolescents differed from non-school going adolescents on stress, depression and anxiety. PMID- 26813518 TI - Genetic evaluation of male infertility. AB - Men with severe oligospermia (<5 million sperm/mL ejaculate fluid) or azoospermia should receive genetic testing to clarify etiology of male infertility prior to treatment. Categorization by obstructive azoospermia (OA) or non-obstructive azoospermia (NOA) is critical since genetic testing differs for the former with normal testicular function, testicular volume (~20 mL), and follicle-stimulating hormone (FSH) (1-8 IU/mL) when compared to the latter with small, soft testes and increased FSH. History and physician examination along with laboratory testing (following appropriate genetic counseling) is critical to accurate selection of genetic testing appropriate for azoospermia due to primary testicular failure as compared with congenital hypogonadotropic hypogonadism (HH). Genetic testing options include cystic fibrosis transmembrane conductance regulator (CFTR) testing for men with congenital absence of the vas, while karyotype, Y chromosome microdeletions (YCMD), and other specific genetic tests may be warranted depending on the clinical context of severe oligospermia or NOA. The results of genetic testing guide management options. The most recent techniques for genetic analysis, including sperm microRNA (miRNA) and epigenetics, are forming the foundation for future genetic diagnosis and therapeutic targets in male infertility. PMID- 26813519 TI - Morbillivirus and henipavirus attachment protein cytoplasmic domains differently affect protein expression, fusion support and particle assembly. AB - The amino-terminal cytoplasmic domains of paramyxovirus attachment glycoproteins include trafficking signals that influence protein processing and cell surface expression. To characterize the role of the cytoplasmic domain in protein expression, fusion support and particle assembly in more detail, we constructed chimeric Nipah virus (NiV) glycoprotein (G) and canine distemper virus (CDV) haemagglutinin (H) proteins carrying the respective heterologous cytoplasmic domain, as well as a series of mutants with progressive deletions in this domain. CDV H retained fusion function and was normally expressed on the cell surface with a heterologous cytoplasmic domain, while the expression and fusion support of NiV G was dramatically decreased when its cytoplasmic domain was replaced with that of CDV H. The cell surface expression and fusion support functions of CDV H were relatively insensitive to cytoplasmic domain deletions, while short deletions in the corresponding region of NiV G dramatically decreased both. In addition, the first 10 residues of the CDV H cytoplasmic domain strongly influence its incorporation into virus-like particles formed by the CDV matrix (M) protein, while the co-expression of NiV M with NiV G had no significant effect on incorporation of G into particles. The cytoplasmic domains of both the CDV H and NiV G proteins thus contribute differently to the virus life cycle. PMID- 26813520 TI - Insights about weight loss-induced metabolic adaptation. PMID- 26813521 TI - Gender Norms and Obesity: Incorporating Gender Norms Change Into Clinical Interventions. PMID- 26813522 TI - The critical period for brown adipocyte development: Genetic and environmental influences. AB - OBJECTIVE: The current review summarizes recent advances in the origin of brown adipocytes in rodents and humans. METHODS: This review describes recent insights into induction of the brown adipocyte phenotype (BAP) in white fat (WAT) revealed by murine studies during the early postnatal period and reversible temperature transitions. The origin of adipocytes and identity of progenitors as indicated by lineage tracing experiments are reviewed. RESULTS: We describe a genetic model for brown adipocyte development that involves the appearance of brown adipocytes in WAT at 21 days of age and a mechanism of post-weaning involution relevant for acquisition of the BAP in fully functional WAT in mice. Under normal physiological conditions, the BAP is dormant with the potential to be stimulated by changes in the external environment. Current evidence for the acquisition of brown adipocytes by interconversion of mature adipocytes versus de novo recruitment of progenitors suggests that mechanisms for acquisition of the BAP in WAT in mice are depot-specific and controlled by allelic variation. CONCLUSIONS: Although the BAP is highly variable among mice, there is no information on genetic variability in the expression of brown adipocytes in humans. Thus, deeper understanding of genetic mechanisms underlying development of functional brown adipocytes is crucial. PMID- 26813523 TI - Physical activity and weight loss are independent predictors of improved insulin sensitivity following energy restriction. AB - OBJECTIVE: The role of physical activity and the joint effect with sleep duration on insulin sensitivity (IS) during energy restriction followed by weight maintenance were determined. METHODS: One hundred and two subjects (28 males) (mean +/- SD age: 40 +/- 9 years; BMI: 31.9 +/- 3.0 kg/m(2) ) followed a very-low energy diet for 8 weeks, followed by a 44-week period of weight maintenance. Body composition (three-compartment model based on body weight, total body water, and body volume), physical activity (accelerometry), sleep (questionnaire, Epworth Sleepiness Scale), and fasting plasma insulin and glucose concentrations were assessed before the diet and at 8, 20, and 52 weeks after the start. RESULTS: Compared to baseline, IS was improved significantly after 8 weeks (P < 0.001) and was higher after 20 weeks (P < 0.001) and 52 weeks (P < 0.05). After 8, 20, and 52 weeks, 23% (P < 0.01), 19% (P < 0.05), and 13% (P < 0.05), respectively, of the variance in IS improvement was explained by weight loss percentage and change in physical activity counts. CONCLUSIONS: Maintaining daily physical activity during energy restriction is as important as weight loss itself in the improvement of IS; there was no additional effect of change in sleep duration. During weight maintenance, improved IS is maintained better if physical activity returns to baseline or higher. PMID- 26813524 TI - The effect of rate of weight loss on long-term weight regain in adults with overweight and obesity. AB - OBJECTIVE: To investigate the effect of rate of weight loss, with similar total weight loss, on weight regain in individuals with overweight and obesity. METHODS: Fifty-seven participants (BMI: 28-35 kg/m(2) ) underwent a dietary intervention (DI). They were randomized to a low-calorie diet (LCD; 1250 kcal/day) for 12 weeks (slow weight loss) or a very-low-calorie diet (VLCD; 500 kcal/day) for 5 weeks (rapid weight loss) (weight loss (WL) period) followed by a 4-week weight-stable (WS) period and 9 months follow-up. Body weight and body composition (BodPod) were determined at study start and after each period. RESULTS: Weight change was similar in both groups after WL (LCD: -8.2 kg and VLCD: -9.0 kg, P = 0.24). Weight regain after follow-up was not significantly different between groups (LCD: 4.2 kg and VLCD: 4.5 kg, P = 0.73). Percentage fat free mass loss (%FFML) was higher in the VLCD-group compared to the LCD-group after DI (8.8% and 1.3%, respectively, P = 0.034) and was associated with weight regain during follow-up in the whole group (r = 0.325, P = 0.018). CONCLUSIONS: The present study showed that, with similar total weight loss, rate of weight loss did not affect weight regain. However, %FFML after DI was associated with weight regain. PMID- 26813525 TI - Dietary fat restriction increases fat taste sensitivity in people with obesity. AB - OBJECTIVE: Individuals with obesity may be less sensitive to the taste of fat, and it is hypothesized that this is due to excess dietary fat intake. This study assessed the effect of a 6-week low-fat (LF) or portion control (PC) diet matched for weight loss on fat taste thresholds, fat perception, and preference in people with overweight/obesity. METHODS: Participants (n = 53) completed a randomized dietary intervention and consumed either a LF diet (25% fat) or PC diet (33% fat) for 6 weeks. Fat taste thresholds (lowest detectable fat concentration), fat perception (discrimination ability), preference, and anthropometry were assessed at baseline and week 6. RESULTS: Consumption of a LF diet (n = 26) and PC diet (n = 27) reduced participants' weight (P < 0.001), with no significant differences between groups (LF, -2.9%, PC, -2.7%). Both diets resulted in a decrease in fat taste thresholds (P = 0.014), and the effect tended to be stronger in the LF diet vs. the PC diet (P = 0.060). The ability to perceive different fat concentrations in foods was increased after the LF diet only (P = 0.017); however, food preference did not change on either diet. CONCLUSIONS: A PC and LF diet both increase fat taste sensitivity in people with overweight/obesity, with the strongest effect after the LF diet. PMID- 26813526 TI - Adipose tissue R2* signal is increased in subjects with obesity: A preliminary MRI study. AB - OBJECTIVE: Circulating and adipose tissue markers of iron overload are increased in subjects with obesity. The aim is to study iron signals in adipose tissue. METHODS: Adipose tissue R2* values and hepatic iron concentration (HIC) were evaluated using magnetic resonance imaging (MRI) in 23 middle-aged subjects with obesity and 20 subjects without obesity. RESULTS: Subcutaneous (SAT) and visceral adipose tissue (VAT) R2* were increased in subjects with obesity (P = 0.004 and P = 0.008) and correlated significantly and positively with HIC in all subjects. Strikingly, most of the associations of liver iron with metabolic parameters were replicated with SAT and VAT R2*. BMI, waist circumference, fat mass, HOMA value, and C-reactive protein positively correlated with HIC and SAT and VAT R2*. BMI or percent fat mass (but not insulin resistance) contributed independently to 26.8 34.8% of the variance in sex- and age-adjusted SAT or VAT R2* (beta > 0.40, P < 0.005). Within subjects with obesity, total cholesterol independently contributed to 14.8% of sex- and age-adjusted VAT iron variance (beta = 0.50, P = 0.025). CONCLUSIONS: Increased R2* in adipose tissue, which might indicate iron content, runs in parallel to liver iron stores of subjects with obesity. VAT iron seems also associated with serum cholesterol within subjects with obesity. PMID- 26813527 TI - Weight loss predictability by plasma metabolic signatures in adults with obesity and morbid obesity of the DiOGenes study. AB - OBJECTIVE: Aim is to predict successful weight loss by metabolic signatures at baseline and to identify which differences in metabolic status may underlie variations in weight loss success. METHODS: In DiOGenes, a randomized, controlled trial, weight loss was induced using a low-calorie diet (800 kcal) for 8 weeks. Men (N = 236) and women (N = 431) as well as groups with overweight/obesity and morbid obesity were studied separately. The relation between the metabolic status before weight loss and weight loss was assessed by stepwise regression on multiple data sets, including anthropometric parameters, NMR-based plasma metabolites, and LC-MS-based plasma lipid species. RESULTS: Maximally, 57% of the variation in weight loss success can be predicted by baseline parameters. The most powerful predictive models were obtained in subjects with morbid obesity. In these models, the metabolites most predictive for weight loss were acetoacetate, triacylglycerols, phosphatidylcholines, specific amino acids, and creatine and creatinine. This metabolic profile suggests that high energy metabolism activity results in higher amounts of weight loss. CONCLUSIONS: Possible predictive (pre diet) markers were found for amount of weight loss for specific subgroups. PMID- 26813528 TI - Ahnak stimulates BMP2-mediated adipocyte differentiation through Smad1 activation. AB - OBJECTIVE: Previous reports have indicated that Ahnak-deficient mice were protected from high-fat diet-induced obesity. However, the molecular mechanism in which Ahnak mediates adipocyte differentiation and high-fat diet-induced obesity is unclear. METHODS: Adipocytes from Ahnak knockout (Ahnak(-/-) ) mice and knockdown of Ahnak in C3H10T1/2 were used to investigate the function of Ahnak in adipocyte differentiation. Ahnak-induced adipocyte differentiation was analyzed by Oil Red O staining. RESULTS: Adipocytes from Ahnak(-/-) mice were smaller than those from wild-type mice. Silencing of Ahnak in C3H10T1/2 and adipose tissue derived mesenchymal stem cells (ADSCs) from Ahnak(-/-) mice showed severely impaired adipocyte differentiation. Down-regulation of Ahnak in C3H10T1/2 cells and ADSCs from Ahnak(-/-) mice attenuated the phosphorylation and nuclear localization of Smad1 in response to BMP2, whereas Ahnak overexpression in 3T3-L1 cells significantly increased Smad1 activation. Because PPARgamma is a well-known transcriptional factor in adipocyte differentiation, the PPARgamma expression in Ahnak-mediated adipocyte differentiation was investigated. Transfection of C3H10T1/2 cells with Ahnak siRNA resulted in reduced PPARgamma expression apparently through inhibited binding of Smad1 to the Smad1-binding site in the PPARgamma promoter. These results suggest that Ahnak regulates adipogenesis by regulating Smad1-dependent PPARgamma expression. CONCLUSIONS: A molecular mechanism was proposed in which Ahnak regulates adipocyte differentiation through Smad1 activation. PMID- 26813529 TI - Subcutaneous fat mass in infancy and cardiovascular risk factors at school-age: The generation R study. AB - OBJECTIVE: To examine the associations of infant subcutaneous fat with cardiovascular risk factors at school-age. METHODS: In a population-based prospective cohort study among 808 children, total subcutaneous fat (sum of biceps, triceps, suprailiacal, and subscapular skinfold thicknesses) and central to-total subcutaneous fat ratio (sum of suprailiacal and subscapular skinfold thicknesses/total subcutaneous fat) at 1.5 and 24 months were estimated. At 6 years, body mass index, blood pressure, cholesterol, triglycerides, and insulin levels were measured. RESULTS: Infant subcutaneous fat measures were not associated with childhood blood pressure, triglycerides, or insulin levels. A 1 standard-deviation score (SDS) higher total subcutaneous fat at 1.5 months was, independently of body mass index, associated with lower low-density lipoprotein (LDL)-cholesterol levels at 6 years. In contrast, a 1-SDS higher total subcutaneous fat at 24 months was associated with higher total-cholesterol [difference 0.13 (95% confidence interval (CI) 0.03, 0.23) SDS] and LDL cholesterol levels [difference 0.12 (95% CI 0.02, 0.21) SDS] at 6 years. There were no associations of central-to-total subcutaneous fat ratio with childhood cholesterol levels. CONCLUSIONS: These results suggest that infant total subcutaneous fat is weakly associated with cholesterol levels at school-age. Further studies are needed to assess the long-term cardiometabolic consequences of infant body fat. PMID- 26813530 TI - Gender expression associated with BMI in a prospective cohort study of US adolescents. AB - OBJECTIVE: To examine the relationship between gender expression (GE) and BMI in adolescence. METHODS: Repeated measures of weight-related behaviors and BMI were collected from 1996 to 2011 via annual/biennial self-report surveys from youth aged 10 to 23 years (6,693 females, 2,978 males) in the longitudinal Growing Up Today Study. GE (very conforming [referent], mostly conforming, nonconforming) was assessed in 2010/11. Sex-stratified, multivariable linear models estimated GE group differences in BMI and the contribution of sexual orientation and weight related exposures to group differences. Models for males included interaction terms for GE with age. RESULTS: In females, mostly conforming youth had 0.53 kg m(-2) and nonconforming had 1.23 kg m(-2) higher BMI; when adding adjustment for sexual orientation and weight-related exposures, GE group estimates were attenuated up to 8% and remained statistically significant. In males, mostly conforming youth had -0.67 kg m(-2) and nonconforming had -1.99 kg m(-2) lower BMI (age [in years]) interactions were between -0.09 and -0.14 kg m(-2) ; when adding adjustment for sexual orientation and weight-related exposures, GE group estimates were attenuated up to 11% and remained statistically significant. CONCLUSIONS: GE is a strong independent predictor of BMI in adolescence. Obesity prevention and treatment interventions with youth must address ways that gender norms may reinforce or undermine healthful behaviors. PMID- 26813531 TI - Mid-adulthood cardiometabolic risk factor profiles of sarcopenic obesity. AB - OBJECTIVE: Midlife and contemporaneous cardiometabolic risk factors associated with sarcopenic obesity were examined. METHODS: Utilizing BMI and sex-specific 24 h urinary creatinine excretion, 1,019 participants from the Framingham cohorts were categorized as non-sarcopenia non-obese (NSNO), non-obese sarcopenia, non sarcopenic obesity, and sarcopenic obesity. Cardiometabolic risk factors were quantified by standard laboratory assessment cross-sectionally and 10, 20, and 30 years before sarcopenic obesity assessment. RESULTS: NSNO, sarcopenia, obesity, and sarcopenic obesity accounted for 30.0%, 39.6%, 20.0%, and 10.4% of study participants, respectively. Cross-sectionally, participants with sarcopenic obesity had a higher proportion of hypertension, metabolic syndrome, and type 2 diabetes than those with NSNO or sarcopenia (all P < 0.03). Similar patterns were observed retrospectively at 10, 20, and 30 years. Compared with NSNO or sarcopenia, sarcopenic obesity was associated with a higher prevalence of type 2 diabetes at 10 years and hypertension and metabolic syndrome at all three time points before baseline (all P < 0.03). Individuals with sarcopenic obesity had more type 2 diabetes than those with obesity alone at baseline and 10 years prior (all P < 0.001). CONCLUSIONS: Older adults with sarcopenic obesity had more adverse midlife cardiometabolic risks, particularly diabetes 10 years earlier, which suggests the importance of early identification of risk factors associated with sarcopenic obesity. PMID- 26813532 TI - Erratum: Low/No calorie sweetened beverage consumption in the national weight control registry. PMID- 26813533 TI - Erratum: Cell phone intervention for you (CITY): A randomized, controlled trial of behavioral weight loss intervention for young adults using mobile technology. PMID- 26813534 TI - 1-R-2-([1,2,4]Triazolo[1,5-c]quinazoline-2-ylthio)etanon(ol)s: synthesis, bioluminescence inhibition, molecular docking studies, antibacterial and antifungal activity. AB - The increasing mortality due to antibacterial resistance necessitates the search for novel antimicrobial agents. Hence, series of 1-R-2-([1,2,4]triazolo[1,5 c]quinazoline-2-ylthio)etanon(ol)s were synthesized, evaluated by spectral data and studied against St. aureus, M. luteum, E. faecalis, E. aerogenes, P. aeruginosa, C. sakazakii, E.coli, K. pneumonia, hospital Streptococcus spp., C. albicans and A. niger in 100, 500 ug/mL and 100 ug/disk. Substances exhibited moderate toxicity in 0.025, 0.1 and 0.25 mg/mL in bioluminescence inhibition tests of Photobacterium leiognathi. SAR exposed that introduction of 2,4 (Cl)2C6H3-, 2,5-(OMe)2C6H3-, 4-Me-2-iPr-C6H3O- and 3-iPr-C6H4O- fragments and reduction of the pyrimidine ring of R-([1,2,4]triazolo[1,5-c]quinazolin-2 ylthio)alcohols were the best modifications to promote antimicrobial activity. Molecular docking showed their good affinity into the active sites of EcPanK AMPPNP and hDHFR. Hence, reported results will be used for subsequent QSAR model creation and purposeful antimicrobial modification of the strongest compounds. PMID- 26813535 TI - Primary Angiosarcoma of the Breast: An Uncommon Histopathological Subtype. AB - Primary angiosarcoma of the breast is extremely rare malignant tumour of the breast. The cytological and radiological findings are often non specific for diagnosis. Histopathology plays an important role in diagnosis and grading of tumour. Herewith we present a case of 55-year-old postmenopausal woman having history of rapidly enlarging right breast lump with prominent vascularity and associated bluish discolouration of overlying skin. Mammography shows ill defined mass lesion. Fine needle aspiration cytology was done which showed haemorrhagic aspirate with few clusters of highly pleomorphic neoplastic cells. Patient underwent modified radical mastectomy. On histopathological evaluation it showed primary angiosarcoma of the breast, poorly differentiated, grade-III. We are presenting this extremely rare malignancy of breast for its clinical, cytological and histopathological findings. PMID- 26813536 TI - A 7/7 NHS: what price equity? PMID- 26813537 TI - Virulence and antimicrobial resistance of Klebsiella pneumoniae isolated from passerine and psittacine birds. AB - Klebsiella pneumoniae is considered one of the most important Gram-negative opportunistic pathogens. The contact between humans and birds poses health risks to both. The aim of this study was to investigate the resistance and virulence of K. pneumoniae isolates from psittacines and passerines, seized from illegal trade in Brazil. We analysed 32 strains isolated from birds of the orders Psittaciformes and Passeriformes by polymerase chain reaction (PCR) for virulence factor genes. Antibiotic resistance was assessed by disk diffusion assay and PCR. The results indicated that fimH (100%), uge (96.8%), kfu (81.2%) and irp-2 (68.7%) were the most common virulence genes, followed by kpn (46.8%), K2 (43.7%), mrkD (34.3%) and iroN (15.6%). The combination of virulence genes resulted in a great diversity of genotypes and the heterogeneity of the strains is also confirmed in the analysis by amplified fragment length polymorphism. The susceptibility profiles of the K. pneumoniae showed 25% of multiple antibiotic resistance strains. We identified seven strains that presented non-extended spectrum beta lactamase blaSHV variants SHV-1 and SHV-11 and one strain positive to the blaTEM-1 gene. Plasmid-mediated quinolone resistance was present in 10 strains (10/32). The data obtained in this study reveal the pathogenic potential of this pathogen and highlight the need for surveillance and monitoring. PMID- 26813538 TI - Current perspectives on China's national essential medicine system: primary care provider and patient views. AB - BACKGROUND: The National Essential Medicine System (NEMS) is a new policy launched by the Chinese government in 2009. The effects of its introduction have been widely investigated. However, little research has focused on individual patients' perspectives. The purpose of this study was to examine current understanding and opinions of China's NEMS of primary care providers (PCPs) and patients. METHODS: Providers (n = 134) and patients (n = 175) were examined based on self-completed questionnaire surveys conducted in 16 primary healthcare centers in Ningxia, northwestern China. Questions addressed the topics of: participants' socio-demographic characteristics; awareness of NEMS policies; perceptions of NEMS-related changes; satisfactions with NEMS. RESULTS: The patients had a low awareness of NEMS while a majority of providers were familiar with NEMS. All participants were satisfied with the price and quality of essential medicines, but not satisfied with the quantity. Patients felt there had been a decrease in their total medical expenses per visit and improved pharmaceutical services. Most providers perceived no change in their personal or departmental income. The overall satisfaction rate related to NEMS among providers and patients was 92.54 and 93.31%, respectively. Overall there was a link between knowledge about NEMS and satisfaction with the program: patients who had greater knowledge of reimbursement policy, and the providers with greater knowledge of NEMS, reported higher satisfaction. CONCLUSIONS: The findings revealed a high level of satisfaction towards NEMS among primary care providers and patients, which is a reflection of the improvements in the health care system. However, some patients' low awareness of NEMS should be paid attention to, as it could reduce their knowledge of essential medicines and hinder the full potential of NEMS. PMID- 26813539 TI - Survival After Emergency General Surgery: What can We Learn from Enhanced Recovery Programmes? AB - Enhanced recovery after surgery (ERAS) has been adopted by many centres and across whole healthcare systems. The results have shown significant reductions in length of stay and postoperative complications. However, there has been very little change in these factors and mortality in emergency surgery. Can we learn from principles of ERAS for emergency abdominal surgery? PMID- 26813540 TI - Postoperative Elevation of the Neutrophil: Lymphocyte Ratio Predicts Complications Following Esophageal Resection. AB - BACKGROUND: Complications following esophagectomy are a significant source of morbidity. The aim of this study was to investigate the utility of the neutrophil:lymphocyte ratio (NLR) in the early identification of complications following esophagectomy, as compared to other routinely available parameters. METHODS: We performed a retrospective cohort study of patients undergoing Ivor Lewis esophagectomy at a single centre. Baseline characteristics and complications occurring within the first 30 days of surgery were recorded. White blood cell counts and C-reactive protein (CRP) levels immediately following surgery (day 0) and over the subsequent three postoperative days were analysed. RESULTS: Sixty-five patients were included, of whom 29 (45 %) developed complications. The median NLR was similar among patients with and without a complicated recovery on day 0 (12.7 vs 13.6, p = 0.70) and day 1 (10.0 vs 9.3, p = 0.29). Patients who subsequently developed complications had a higher NLR on day 2 (11.8 vs 7.5, p < 0.001) and day 3 (9.0 vs 6.5, p = 0.001) compared to those whose recovery was uncomplicated. Receiver-operating-characteristic plots for the diagnostic performance of the NLR, neutrophil count, lymphocyte count and CRP level at each time point demonstrated that the NLR on day 2 had the greatest discriminatory ability in predicting complications, with an area under the curve of 0.83 (95 % CI 0.73-0.94). An NLR of >8.3 on day 2 had a sensitivity of 93 % and a specificity of 72 % for predicting complications. CONCLUSION: The NLR is a simple and routinely available parameter which has a high sensitivity in the early detection of complications following esophagectomy. PMID- 26813541 TI - Milligan-Morgan (Open) Versus Ferguson Haemorrhoidectomy (Closed): A Systematic Review and Meta-Analysis of Published Randomized, Controlled Trials. AB - OBJECTIVE: The purpose of this article is to systematically analyse the randomized, controlled trials (RCTs) comparing Ferguson or closed haemorrhoidectomy (CH) versus open haemorrhoidectomy (OH) or Milligan-Morgan haemorrhoidectomy in the management of haemorrhoidal disease (HD). METHODS: RCTs on the effectiveness of CH and OH in the management of HD were analysed systematically using RevMan((r)), and combined outcome was expressed as odds ratio (OR) and standardized mean difference. RESULTS: Eleven CRTs encompassing 1326 patients were analysed systematically. There was significant heterogeneity among included trials. Therefore, in the random effects model, CH was associated with a reduced post-operative pain (SMD, -0.36; 95 % CI, -0.64, -0.07; z = 2.45; p = 0.01), faster wound healing (OR, 0.08; 95 % CI, 0.02, 0.24; z = 4.33; p < 0.0001), lesser risk of post-operative bleeding (OR, 0.50; 95 % CI, 0.27, 0.91; z = 2.27; p < 0.02) and prolonged duration of operation (SMD, 6.10; 95 % CI, 3.21, 8.98; z = 4.13; p < 0.0001). But the variables such as pain on defecation (SMD, 0.33; 95 % CI, -0.68, 0.03; z = 1.82; p = 0.07), length of hospital stay, post operative complications, HD recurrence and risk of surgical site infection were similar in both groups. CONCLUSION: CH has clinically measurable advantages over OH in terms of reduced post-operative pain, lower risk of post-operative bleeding and faster wound healing. PMID- 26813542 TI - Laparoscopic simple prostatectomy with prostatic urethra preservation for benign prostatic hyperplasia. AB - OBJECTIVE: Laparoscopic simple prostatectomy for large volume benign prostatic hyperplasia (BPH) has been reported in the literature and may be a viable alternative to open surgery for large prostate glands. While previous publications have shown comparable outcomes between laparoscopic and open simple prostatectomy, there have been few publications describing improved laparoscopic operative technique to further improve these outcomes. The authors describe a novel technique of prostatic urethra preservation during laparoscopic simple prostatectomy. MATERIALS AND METHODS: From January 2006 to September 2009, laparoscopic simple prostatectomy with prostatic urethra preservation was performed in 51 patients with symptomatic BPH. This technique included extraperitoneal insufflation of the retropubic space by balloon dilation, placement of five trocars in an inverted U shape, transverse prostatic capsular incision, development of a subcapsular plane, and removal of prostatic adenoma with preservation of the prostatic urethra followed by suturing of the prostatic capsule. Demographic, perioperative and outcome data were recorded. RESULTS: The mean operative time was 126+/-51.98 min and the estimated blood loss was 232.55+/ 199.54 mL. Significant improvements were noted in the International Prostate Symptom Score (IPSS), quality of life (QOL) questionnaires and maximum flow rate (Qmax) of patients three months after surgery. No incontinence was reported in any patient. Moreover, there was no significant difference in the 5-Item International Index of Erectile Function (IIEF-5) score pre- and post- operatively in patients who had erectile function before surgery and no patient complained of retrograde ejaculation during the postoperative follow-up period. CONCLUSIONS: Laparoscopic simple prostatectomy with prostatic urethra preservation for benign prostatic hyperplasia is feasible and reproducible. With this technique, postoperative morbidity can be reduced and antegrade ejaculation preserved. PMID- 26813543 TI - [New strategies are warranted to achieve the World Heart Federation "25*25" roadmaps on reducing hypertension--related mortality in China]. PMID- 26813544 TI - [Development tendency of domestic professional cardiac rehabilitation: clinical practice situation from today to tomorrow]. PMID- 26813545 TI - [Familial hypercholesterolaemia: urgent to establish a global united front]. PMID- 26813546 TI - [The expert consensus on medication management in patients with stable coronary heart disease undergoing cardiac rehabilitation]. PMID- 26813547 TI - [Chinese expert consensus on the diagnosis and treatment of mental stress-induced myocardial ischemia in patients with stable coronary artery disease]. PMID- 26813548 TI - [Status of beta-blocker use and heart rate control in Chinese patients with stable coronary artery disease]. AB - OBJECTIVE: To observe the current status of beta-blocker (BB) use and heart rate control in Chinese patients with stable coronary artery disease (SCAD) based on subgroup data of the prospective observational longitudinal registry of patients with stable coronary artery disease (CLARIFY). METHODS: The CLARIFY study is an international prospective observational registry of outpatients with SCAD. From November 2009 to July 2010, patients with SCAD were enrolled, and demographic information, clinical indicators, medication and blood flow reconstruction were collected. Patients were divided in three mutually exclusive categories by baseline pulse palpation heart rate(HR)<=60 beats per minute (bpm)(n=397), 61-69 bpm(n=782), and >=70 bpm(n=1 443). The patients were also divided into taking BB or not taking BB groups. The aim of present study is to describe and analyze the current status and factors related to the HR control and BB use in the Chinese subgroup of CLARIFY. RESULTS: A total of 2 622 patients were enrolled from 56 centers across China. The mean age was (63.6+/-10.3) years old with 75.6% (1 983) male patients, 55.0% (1 443) patients had HR>=70 bpm. Mean HR measure by electrocardiogram(ECG) was (69.4+/-10.2)bpm, 50.9% (1 334 cases) patients had myocardial infarction(MI) history. A total of 21.9%(575 cases) patients had anginal symptoms; coronary angiography was performed in 88.8%(2 327 cases) of the patients. 76.2%(1 997 cases) patients were treated with BB (any molecule and any dose), 2.7% (70 cases) with digoxin or derivatives, 3.9% (103 cases) with verapamil or diltiazem, and 1.8% (47 cases) with amiodarone or dronedarone and 0.1%(2 cases) received ivabradine. BB use was similar among 3 HR groups(P>0.05). The independent risk factors associated with HR>=70 bpm were diabetes(OR=1.31), current smoker(OR=1.57), chronic heart failure(CHF) with NYHA III (OR=2.13) and increased diastolic blood pressure (OR=1.30). Conversely, high physical activity (OR=0.61), former smoker (OR=0.76) and history of percutaneous coronary intervention(PCI, OR=0.80) were associated with lower risk of HR>=70 bpm (all P<0.05). The independent risk factors associated with non-BB use were older age (OR=1.11, 95%CI 1.01-1.47, P=0.005), lower diastolic blood pressure (OR=1.47, 95%CI 1.32-1.68, P=0.012), no history of MI (OR=1.86, 95%CI 1.43-2.44, P<0.001) or PCI (OR=1.94, 95%CI 1.55-3.73, P<0.001), asthma/chronic obstructive pulmonary disease (OR=1.32, 95%CI 1.15-1.99, P<0.001). CONCLUSIONS: A total of 76.2% Chinese SCAD patients received BB medication but more than half of them did not reach the optimal HR. Clinical characteristics including diabetes, current smoker, CHF, increased diastolic blood pressure and no PCI were associated with poorly controlled HR(>=70 bpm). More efforts including adjusting the type and dose of heart rate lowering drugs are needed to achieve optimal HR control in Chinese SCAD patients. Clinical Trail Registry International Standard Randomized Controlled Trial, ISRCTN43070564. PMID- 26813549 TI - [Related factors of optical coherence tomography detected in-stent heterogonous neointima]. AB - OBJECTIVE: To explore the related factors of optical coherence tomography (OCT) detected in-stent heterogeneous neointimal in coronary stents. METHODS: A total of 143 cases of coronary heart disease patients with OCT detected in-stent neointimal hyperplasia in Fuwai hospital from September 2009 to April 2012 were included in this study and patients data were retrospectively analyzed. Patients were divided into heterogeneous intima group(26 cases) and homogeneous intima group(117 cases)according to neointimal characteristics. Clinical features and OCT characteristics of the 2 groups were compared and binary logistic regression analysis was performed to analyze the risk factors of in-stent heterogonous neointimal hyperplasia. RESULTS: Compared to homogeneous intima group, patients in heterogeneous intima group had significantly higher cholesterol level ((5.31+/ 1.11)mmol/L vs.(4.70+/-0.94)mmol/L, P=0.005), low-density lipoprotein cholesterol level ((2.57+/-0.87)mmol/L vs.(2.29+/-0.46)mmol/L, P=0.021) and triglyceride level (2.12(1.82-2.87)mmol/L vs. 1.90(1.73-2.11)mmol/L, P=0.015). Moreover, the percent of percutaneous coronary intervention (PCI) because of acute coronary syndrome (23.1%(6/26) vs. 6.8%(8/117), P=0.022) and the thin cap neoatheroma (5.8%(28/481)vs. 3.9%(89/2 276), P=0.043) were also significantly higher in heterogeneous intima group than in homogeneous intima group. Binary logistic regression analysis showed that low-density lipoprotein cholesterol (OR=2.74, 95%CI 1.04-7.24, P=0.042), triglyceride (OR=2.88, 95%CI 1.05-7.89, P=0.040), PCI for acute coronary syndrome (OR=12.74, 95%CI 2.69-60.49, P=0.001), and cerebrovascular disease (OR=13.09, 95%CI 2.16-79.53, P=0.005) were risk factors for in-stent heterogenous intima. Time post stent implantation was protective factor for in-stent heterogenous intima (OR=0.63, 95%CI 0.42-0.96, P=0.033). CONCLUSION: OCT detected heterogeneous intima is correlated with level of blood lipid, PCI for acute coronary syndrome and history of cerebrovascular disease, and it may lead to unstable intima. PMID- 26813550 TI - [Impact of plasma homocysteinemia on contrast-induced nephropathy after percutaneous coronary intervention in patients with coronary syndrome]. AB - OBJECTIVE: To explore the impact of plasma homocysteinemia(Hcy) on contrast induced nephropathy (CIN) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) patients. METHODS: Consecutive 684 ACS patients undergoing first PCI in our department between January 2013 and December 2014 were prospectively enrolled.Patients were divided into 2 groups according to the pre-procedural plasma Hcy level: high-Hcy group (Hcy>=10 MUmol/L, n=404) and control group (Hcy<10 MUmol/L, n=280). The CIN was defined as serum creatinine >= 44.2 MUmol/L or 25% increase compared to baseline within 48-72 h after PCI.The baseline clinical data and the ratio of CIN were compared between the 2 groups.Multivariate logistic regression analysis was used to define the independent risk factors for CIN. RESULTS: CIN occurred in 133(19.4%) out of 684 enrolled patients, and the incidence of CIN was significantly higher in high Hcy group than in the control group (22.0%(89/404)vs. 15.7%(44/280), P=0.040). After adjusting the confounding factors, including age, acute myocardial infarction, co morbidities(hypertension, diabetes mellitus, and old myocardial infarction), laboratory examination (level of cystatin C and uric acid), glomerular filtration rate, left ventricular ejection fraction, angiographic and procedural characteristics (3 diseased vessels, multiple stent implantation), treatment at admission (spironolactone, digoxin), multivariate logistic regression analysis showed that high Hcy was independently associated with the development of CIN (OR=1.70, 95%CI 1.60-2.64, P=0.021). CONCLUSION: Elevated Hcy prior PCI is an independent risk factor of CIN in ACS patients undergoing first PCI. PMID- 26813551 TI - [Carotid plaque characteristics detected with 3.0T high resolution nuclear magnetic resonance imaging in patients with coronary artery disease]. AB - OBJECTIVE: To assess the value of detecting the compositional features of carotid atherosclerotic plaques by 3.0T high resolution magnetic resonance imaging (MRI) in patients with coronary artery disease (CAD). METHODS: Consecutive 104 patients with coronary atherosclerosis confirmed by coronary angiography were prospectively recruited from January 2013 to January 2015 in Tiantan hospital. All patients were imaged with 3.0T high resolution MRI system. After exclusion patients with poor image quality, 97 patients were divided into 3 groups according to the degree of coronary artery stenosis: coronary atherosclerosis group (coronary stenosis between 1%-49%, n=16); single-vessel lesion group (single vessel lesion with stenosis between 50%-100%, n=48); multi-vessel lesion group (two or three vessel lesions with stenosis between 50%-100% or left main stem disease, n=33). The prevalence of total carotid plaque, calcified plaque, lipid-rich necrotic core, intra-plaque hemorrhage, plaque ulcer and rupture were compared among 3 groups. RESULTS: The prevalence of total carotid plaque (81.3%(13/16), 72.9%(35/48), and 93.9%(31/33)) and calcified plaque (50.0%(8/16), 35.4%(17/48), and 42.4%(14/33)) were similar among the 3 groups (both P>0.05). The prevalence of carotid lipid-rich necrotic core in coronary atherosclerosis group was significantly lower than in single-vessel lesion group (18.8%(3/16) vs. 64.6%(31/48), P<0.01) and multi-vessel lesion group(18.8%(3/16) vs. 69.7%(23/33), P<0.01), but there was no significant difference between single-vessel lesion group and multi-vessel lesion group(P>0.05). Intra-plaque hemorrhage was detected in 2 patients of multi-vessel lesion group. There was no plaque ulcer or rupture in this cohort. CONCLUSION: Carotid plaque features are associated with the severity of coronary atherosclerosis in CAD patients. PMID- 26813552 TI - [Changes of hospitalization rates and in-hospital mortality for coronary heart disease in Beijing from 2007-2012]. AB - OBJECTIVE: To observe the changes of hospitalization rates and in-hospital mortality for coronary heart disease (CHD) in Beijing from 2007-2012. METHODS: Patients hospitalized for CHD in Beijing from 1 January 2007 to 31 December 2012 were identified from"The Cardiovascular Disease Surveillance System in Beijing". In total, 421 929 patients aged >=25 years of permanent Beijing residents were admitted for CHD in Beijing during the 6 years. After excluding duplicate records and validation for the completeness and accuracy of the records, the hospitalization rates for CHD and in-hospital CHD mortality were analyzed. Trends in hospitalization rates and the in-hospital mortality for CHD were analyzed with Poisson regression models. RESULTS: The age-standardized average hospitalization rate of CHD was 515.3 per 100 000 population in patients aged >=25 years in Beijing. During the six years, an increasing trend was observed in the hospitalization rates for CHD after adjusting the age and gender (P<0.001). The age-standardized hospitalization rates of CHD increased by 43.0% in the past six years. The greatest increases of hospitalization rates were noted in both men and women between 45 to 54 years. The age-standardized in-hospital mortality decreased from 3.3% to 2.2% over the time (P<0.001), with a in-hospital mortality reduction for acute myocardial infarction from 11.3% to 8.5%. CONCLUSIONS: An increasing trend in hospitalization rate was observed during 2007-2012 for Beijing residents aged >=25 years, indicating an urgent need in CHD prevention in Beijing. The in-hospital mortality reduction during this period might reflect the improvement in the in-hospital treatment modalities of CHD. PMID- 26813553 TI - [Relationship between electrocardiographic and genetic mutation (MYH7-H1717Q, MYLK2-K324E and KCNQ1-R190W) phenotype in patients with hypertrophic cardiomyopathy]. AB - OBJECTIVE: To explore the relationship between electrocardiographic (ECG) and genetic mutations of patients with hypertrophic cardiomyopathy (HCM), and early ECG changes in HCM patients. METHODS: Clinical, 12-lead ECG and echocardiographic examination as well as genetic examinations were made in a three-generation Chinses HCM pedigree with 8 family members (4 males). The clinical characterization and ECG parameters were analyzed and their relationship with genotypes in the family was explored. RESULTS: Four missense mutations (MYH7 H1717Q, MYLK2-K324E, KCNQ1-R190W, TMEM70-I147T) were detected in this pedigree. The proband carried all 4 mutations and 5 members carried 2 mutations. Corrected QTc interval of KCNQ1-H1717Q carriers was significantly prolonged and was consistent with the ECG characterization of long QT syndrome. MYLK2-K324E and KCNQ1-R190W carriers presented with Q wave and(or) depressed ST segment, as well as flatted or reversed T waves in leads from anterolateral and inferior ventricular walls. ECG results showed ST segment depression, flat and inverted T wave in the gene mutation carriers with normal echocardiographic examination results. ECG and echocardiographic results were normal in TMEM70-I147T mutation carrier. CONCLUSIONS: The combined mutations of the genes associated with cardiac ion channels and HCM are linked with the ECG phenotype changes in this HCM pedigree. The variations in ECG parameters due to the genetic mutation appear earlier than the echocardiography and clinical manifestations. Variation in ECG may become one of the indexes for early diagnostic screening and disease progression of the HCM gene mutation carriers. PMID- 26813554 TI - [Experiences of applying home monitoring for cardiac implantable electronic devices]. AB - OBJECTIVE: To observe the results of remote home monitoring for cardiac implantable electronic devices (CIED). METHODS: From November 2009 to July 2014, 37 patients implanted with home monitoring system CIED were enrolled, and 31 cases were implanted with dual chamber pacemakers, 2 with cardiac resynchronization therapy(CRT) and 4 with implantable cardioverter defibrillator (ICD). All patients received clinical routine follow-up.Data was automatic transmitted daily by remote home monitoring system, while special alarm events were transmitted at any time.The success rate of data transmission, abnormal events monitoring and pacing parameter changes were analyzed. RESULTS: A total of 37 patients (24 males, mean age (70.0+/-9.6) years) were enrolled.Average follow up time was (902+/-404) days.Success rate of data transmission was 97.6% (32 574), failed data transmission rate was 2.4% (801). Ninth-nine alerts were transmitted from 28 patients (75.7%), including 80 (80.8%) disease-related alerts and 19 (19.2%) system-related alerts.Average detection time of atrial fibrillation by remote home monitoring system to last clinical routine follow-up was 62 (19-120) days.There was no significant change in ventricular threshold, atrial and ventricle sensing during acute, subacute and chronic phases post the application of the steroid-eluting leads(all P>0.05). CONCLUSIONS: The success rate of data transmission for CIED with remote home monitoring system is efficient, abnormal events can be timely detected.Meanwhile, remote home monitoring system also verified the stability of pacing parameters during acute, subacute and chronic phases post the application of the steroid-eluting leads. PMID- 26813555 TI - [The impact of long- and short-time blood pressure variability on glomerular filtration rate in elderly population]. AB - OBJECTIVE: To investigate the impact of long-time and short-time blood pressure variability (BPV) on glomerular filtration rate (eGFR) in elderly population. METHODS: A total of 2 464 participants aged of >=60 years old without history of stroke and coronary heart disease were selected with random sampling method from the individuals underwent health check up in Tangshan Kailuan Hospital, Kailuan Linxi Hospital, Kailuan Zhaogezhuang Hospital between 2006 and 2013. The study participants were asked to join a face-to-face interview every two years. Long time BPV was defined as the standard deviation of all SBP values at the baseline visit and following visits, short-time BPV was defined as the standard deviation of day time blood pressure and night time blood pressure which was derived from 24 hours ambulatory blood pressure monitoring. Multivariate linear regression models were used to test the impact of long- and short-time BPV on eGFR. RESULTS: The study included 3 participants groups including the long-time SBPV group (2 279 participants), the short-time SBPV group (1 636 participants) and the long- plus short-time SBPV group (1 632 participants). Participants were further sub grouped by median value (NO.1median value). eGFR in the long time SBPV NO.1 and NO.2 group was 83.19 and 81.49 ml.min(-1).1.73 m(-2) respectively, in the short time SBPV NO.1 and NO.2 group was 83.53 and 80.81ml.min(-1).1.73 m(-2) of the day time, and was 83.20 and 81.14 ml.min( 1).1.73 m(-2) of the night time, respectively. eGFR in the long- plus short-time SBPV NO.1 and NO.2 group was 83.21 and 81.08 ml.min(-1).1.73 m(-2) of the long time SBPV, and was 83.53 and 80.75 ml.min(-1).1.73 m(-2) of the day time, and was 83.18 and 81.11 ml.min(-1).1.73 m(-2) of the night time. Significant linear relationship was found between higher day time SBPV and lower eGFR (P<0.05). After adjusting for confounding parameters including age, sex, body mass index, 1 mmHg(1 mmHg=0.133 kPa) of day time SBPV increase was related 0.21 ml.min(-1).1.73 m(-2) eGFR decrease (P<0.05). CONCLUSION: The higher day time SBPV is associated with reduced eGFR in the elderly population.Clinical Trail Registry Chinese Clinical Trial Registry, ChiCTR-TNC-11001489. PMID- 26813556 TI - [One case of stent-assisted coil embolization of coronary artery aneurysm in a patient with left main bifurcation lesions]. PMID- 26813557 TI - [Anomalous origin of the left coronary artery from the pulmonary artery: a case report]. PMID- 26813558 TI - [A case of bioprosthetic valve endocarditis due to Pichia ohmeri]. PMID- 26813559 TI - [Research progress of relationship between serum bilirubin and coronary heart disease]. PMID- 26813560 TI - [Progress of research in coronary mircochannel identified by optical coherence tomography]. PMID- 26813561 TI - [Assessing the risk of thanscatheter aortic valve replacement for patients with severe aortic stenosis by computed tomography angiography]. PMID- 26813562 TI - Autoantibodies against Linear Epitopes of Myeloperoxidase in Anti-Glomerular Basement Membrane Disease. AB - BACKGROUND AND OBJECTIVES: Approximately 20%-30% of patients with anti-glomerular basement membrane disease present coexisting anti-myeloperoxidase (MPO) autoantibodies. We previously showed the recognition of a linear fragment of the MPO heavy chain N-terminus ((1)H, MPO279-409) in plasma from most double-positive patients. Herein, we investigated the frequency of autoantibodies against overlapping (1)H-derived linear peptides in plasma from patients with anti glomerular basement membrane disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We synthesized 13 overlapping linear peptides ((1)H-1 to (1)H-13) covering MPO279-409. We retrospectively collected plasma samples from 67 patients with anti-glomerular basement membrane disease from 1996 to 2012, and we screened them for IgG autoantibodies by ELISA using intact human MPO and the overlapping peptides as antigens, and we further investigated the clinical significance. Autoantibody binding to the linear MPO structure was confirmed by Western blotting. RESULTS: We followed up the 67 patients until 2015, with a median follow-up time of 10.0 (2.3-36.0) months, and 56 ESRD events occurred among the 67 patients with follow-up data. Plasma from 23.9% (16) of the patients recognized intact human MPO, whereas 62.7% (42) plasma samples recognized MPO279 409 linear peptides. Of the 13 linear peptides, (1)H-4 (44.8%, 30 patients) and (1)H-12 (40.3%, 27 patients) exhibited the highest recognition frequencies. Patients with autoantibodies against (1)H-11 or (1)H-12 (MPO371-400) were older (46.1+/-18.8 versus 34.1+/-16.6 years; P<0.01), had higher serum creatinine upon diagnosis (median 7.8 mg/dl, interquartile range 4.9-12.6 mg/dl versus median 5.4 mg/dl, interquartile range 2.4-7.3 mg/dl; P=0.02), and had a higher probability of progressing to ESRD; however, multivariate Cox regression analysis showed that (1)H-11 or 12 reaction was not an independent risk factor for renal failure (hazard ratio, 1.2; 95% confidence interval, 0.8 to 2.8; P=0.19). CONCLUSIONS: Autoantibodies against linear peptides of MPO can be detected in the majority of patients with anti-glomerular basement membrane disease, and several are associated with disease severity. The potential common pathogenic mechanism between anti-glomerular basement membrane antibodies and anti-MPO autoantibodies in anti-glomerular basement membrane disease requires further investigation. PMID- 26813563 TI - MarsAtlas: A cortical parcellation atlas for functional mapping. AB - An open question in neuroimaging is how to develop anatomical brain atlases for the analysis of functional data. Here, we present a cortical parcellation model based on macroanatomical information and test its validity on visuomotor-related cortical functional networks. The parcellation model is based on a recently developed cortical parameterization method (Auzias et al., [2013]: IEEE Trans Med Imaging 32:873-887), called HIP-HOP. This method exploits a set of primary and secondary sulci to create an orthogonal coordinate system on the cortical surface. A natural parcellation scheme arises from the axes of the HIP-HOP model running along the fundus of selected sulci. The resulting parcellation scheme, called MarsAtlas, complies with dorsoventral/rostrocaudal direction fields and allows inter-subject matching. To test it for functional mapping, we analyzed a MEG dataset collected from human participants performing an arbitrary visuomotor mapping task. Single-trial high-gamma activity, HGA (60-120 Hz), was estimated using spectral analysis and beamforming techniques at cortical areas arising from a Talairach atlas (i.e., Brodmann areas) and MarsAtlas. Using both atlases, we confirmed that visuomotor associations involve an increase in HGA over the sensorimotor and fronto-parietal network, in addition to medial prefrontal areas. However, MarsAtlas provided: (1) crucial functional information along both the dorsolateral and rostrocaudal direction; (2) an increase in statistical significance. To conclude, our results suggest that the MarsAtlas is a valid anatomical atlas for functional mapping, and represents a potential anatomical framework for integration of functional data arising from multiple techniques such as MEG, intracranial EEG and fMRI. PMID- 26813564 TI - miR-15a and miR-24-1 as putative prognostic microRNA signatures for pediatric pilocytic astrocytomas and ependymomas. AB - In the current setting, we attempted to verify and validate miRNA candidates relevant to pediatric primary brain tumor progression and outcome, in order to provide data regarding the identification of novel prognostic biomarkers. Overall, 26 resected brain tumors were studied from children diagnosed with pilocytic astrocytomas (PAs) (n = 19) and ependymomas (EPs) (n = 7). As controls, deceased children who underwent autopsy and were not present with any brain malignancy were used. The experimental approach included microarrays covering 1211 miRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the expression profiles of miR-15a and miR-24-1. The multiparameter analyses were performed with MATLAB. Matching differentially expressed miRNAs were detected in both PAs and EPs, following distinct comparisons with the control cohort; however, in several cases, they exhibited tissue-specific expression profiles. On correlations between miRNA expression and EP progression or outcome, miR-15a and miR-24-1 were found upregulated in EP relapsed and EP deceased cases when compared to EP clinical remission cases and EP survivors, respectively. Taken together, following several distinct associations between miRNA expression and diverse clinical parameters, the current study repeatedly highlighted miR-15a and miR-24-1 as candidate oncogenic molecules associated with inferior prognosis in children diagnosed with ependymoma. PMID- 26813565 TI - The cancer-retina antigen recoverin as a potential biomarker for renal tumors. AB - The renal cell carcinoma is the ninth most common cancer with an increasing occurrence and mortality. Recoverin is the first retina-specific photoreceptor protein that was shown to undergo aberrant expression, due to its promoter demethylation, as a cancer-retina antigen in a number of malignant tumors. In this work, we demonstrated that recoverin is indeed expressed in 68.4 % of patients with different subtypes of renal cell carcinoma, and this expression has tendency to correlate with tumor size. Interestingly, 91.7 % of patients with the benign renal tumor, oncocytoma, express recoverin as well in their tumor. Epigenetic analysis of the recoverin gene promoter revealed a stable mosaic methylation pattern with the predominance of the methylated state, with the exception of -80 and 56 CpG dinucleotides (CpGs). While the recoverin expression does not correlate withoverall survival of the tumor patients, the methylation of the recoverin gene promoter at -80 position is associated with better overall survival of the patients. This work is the first report pointing towards the association of overall survival of renal cell carcinoma (RCC) patients with promoter methylation of a cancer-retina antigen. Taken together, these data allow to consider recoverin as a potential therapeutic target and/or marker for renal tumors. PMID- 26813566 TI - Naive Treg-like CCR7(+) mononuclear cells indicate unfavorable prognosis in hepatocellular carcinoma. AB - Chemokine receptor-like 1 (CCRL1) has the potential in creating a low level of CCL19 and CCL21 to hinder CCR7(+) cell tracking to tumor tissue. Previously, we found a tumor suppressive role of CCRL1 by impairing CCR7-related chemotaxis of tumor cells in human hepatocellular carcinoma (HCC). Here, we reported a contribution of CCR7(+) mononuclear cells in the tumor microenvironment to the progression of disease. Immunohistochemistry was used to investigate the distribution and clinical significance of CCR7(+) cells in a cohort of 240 HCC patients. Furthermore, the phenotype, composition, and functional status of CCR7(+) cells were determined by flow cytometry, immunofluorescence, and in vitro co-culture assays. We found that CCR7(+) mononuclear cells were dispersed around tumor tissue and negatively related to tumoral expression of CCRL1 (P < 0.001, r = 0.391). High density of CCR7(+) mononuclear cells positively correlated with the absence of tumor capsule, vascular invasion, and poor differentiation (P < 0.05). Survival analyses revealed that increased number of CCR7(+) mononuclear cells was significantly associated with worse survival and increased recurrence. We found that CCR7(+) mononuclear cells featured a naive Treg-like phenotype (CD45RA(+)CD25(+)FOXP3(+)) and possessed tumor-promoting potential by producing TGF-beta1. Moreover, CCR7(+) cells were also composed of several immunocytes, a third of which were CD8(+) T cells. CCR7(+) Treg-like cells facilitate tumor growth and indicate unfavorable prognosis in HCC patients, but fortunately, their tracking to tumor tissue is under the control of CCRL1. PMID- 26813567 TI - Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis. AB - AIMS: Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular release. This model allows testing of antifibrotic agents, such as rosiglitazone. METHODS: A total of 20 rabbits underwent contracture forming surgery. Eight weeks later, the animals underwent a surgical capsular release. Ten animals received rosiglitazone (intramuscular initially, then orally). The animals were sacrificed following 16 weeks of free cage mobilisation. The joints were tested biomechanically, and the posterior capsule was assessed histologically and via genetic microarray analysis. RESULTS: There was no significant difference in post-traumatic contracture between the rosiglitazone and control groups (33 degrees (standard deviation (sd) 11) vs 37 degrees (sd14), respectively; p = 0.4). There was no difference in number or percentage of myofibroblasts. Importantly, there were ten genes and 17 pathways that were significantly modulated by rosiglitazone in the posterior capsule. DISCUSSION: Rosiglitazone significantly altered the genetic expression of the posterior capsular tissue in a rabbit model, with ten genes and 17 pathways demonstrating significant modulation. However, there was no significant effect on biomechanical or histological properties.Cite this article: M. P. Abdel. Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis. Bone Joint Res 2016;5:11-17. doi: 10.1302/2046 3758.51.2000593. PMID- 26813568 TI - Increased mortality attributed to Chagas disease: a systematic review and meta analysis. AB - BACKGROUND: The clinical outcomes associated with Chagas disease remain poorly understood. In addition to the burden of morbidity, the burden of mortality due to Trypanosoma cruzi infection can be substantial, yet its quantification has eluded rigorous scrutiny. This is partly due to considerable heterogeneity between studies, which can influence the resulting estimates. There is a pressing need for accurate estimates of mortality due to Chagas disease that can be used to improve mathematical modelling, burden of disease evaluations, and cost effectiveness studies. METHODS: A systematic literature review was conducted to select observational studies comparing mortality in populations with and without a diagnosis of Chagas disease using the PubMed, MEDLINE, EMBASE, Web of Science and LILACS databases, without restrictions on language or date of publication. The primary outcome of interest was mortality (as all-cause mortality, sudden cardiac death, heart transplant or cardiovascular deaths). Data were analysed using a random-effects model to obtain the relative risk (RR) of mortality, the attributable risk percent (ARP), and the annual mortality rates (AMR). The statistic I(2) (proportion of variance in the meta-analysis due to study heterogeneity) was calculated. Sensitivity analyses and publication bias test were also conducted. RESULTS: Twenty five studies were selected for quantitative analysis, providing data on 10,638 patients, 53,346 patient-years of follow-up, and 2739 events. Pooled estimates revealed that Chagas disease patients have significantly higher AMR compared with non-Chagas disease patients (0.18 versus 0.10; RR = 1.74, 95% CI 1.49-2.03). Substantial heterogeneity was found among studies (I(2) = 67.3%). The ARP above background mortality was 42.5%. Through a sub-analysis patients were classified by clinical group (severe, moderate, asymptomatic). While RR did not differ significantly between clinical groups, important differences in AMR were found: AMR = 0.43 in Chagas vs. 0.29 in non Chagas patients (RR = 1.40, 95% CI 1.21-1.62) in the severe group; AMR = 0.16 (Chagas) vs. 0.08 (non-Chagas) (RR = 2.10, 95% CI 1.52-2.91) in the moderate group, and AMR = 0.02 vs. 0.01 (RR = 1.42, 95% CI 1.14-1.77) in the asymptomatic group. Meta-regression showed no evidence of study-level covariates on the effect size. Publication bias was not statistically significant (Egger's test p=0.08). CONCLUSIONS: The results indicate a statistically significant excess of mortality due to Chagas disease that is shared among both symptomatic and asymptomatic populations. PMID- 26813569 TI - Sporadic medullary microcarcinoma in a male patient with concurrent Hashimoto's hypothyroidism and Kikuchi disease. PMID- 26813570 TI - Urachal abscess precipitated as acute pyelonephritis in an adult patient with diabetes. PMID- 26813571 TI - Prosthetic knee joint infection due to Listeria monocytogenes bacteremia in a diabetic female. PMID- 26813572 TI - Angiographic spontaneous pseudo-resolution of a coronary artery aneurysm after implantation of a sirolimus-eluting stent. PMID- 26813573 TI - Solitary bone and brain metastasis in a patient with papillary thyroid carcinoma mimicking cavernous angioma. PMID- 26813574 TI - Phylogenomic exploration of the relationships between strains of Mycobacterium avium subspecies paratuberculosis. AB - BACKGROUND: Mycobacterium avium subspecies paratuberculosis (Map) is an infectious enteric pathogen that causes Johne's disease in livestock. Determining genetic diversity is prerequisite to understanding the epidemiology and biology of Map. We performed the first whole genome sequencing (WGS) of 141 global Map isolates that encompass the main molecular strain types currently reported. We investigated the phylogeny of the Map strains, the diversity of the genome and the limitations of commonly used genotyping methods. RESULTS: Single nucleotide polymorphism (SNP) and phylogenetic analyses confirmed two major lineages concordant with the former Type S and Type C designations. The Type I and Type III strain groups are subtypes of Type S, and Type B strains are a subtype of Type C and not restricted to Bison species. We found that the genome-wide SNPs detected provided greater resolution between isolates than currently employed genotyping methods. Furthermore, the SNP used for IS1311 typing is not informative, as it is likely to have occurred after Type S and C strains diverged and does not assign all strains to the correct lineage. Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) differentiates Type S from Type C but provides limited resolution between isolates within these lineages and the polymorphisms detected do not necessarily accurately reflect the phylogenetic relationships between strains. WGS of passaged strains and coalescent analysis of the collection revealed a very high level of genetic stability, with the substitution rate estimated to be less than 0.5 SNPs per genome per year. CONCLUSIONS: This study clarifies the phylogenetic relationships between the previously described Map strain groups, and highlights the limitations of current genotyping techniques. Map isolates exhibit restricted genetic diversity and a substitution rate consistent with a monomorphic pathogen. WGS provides the ultimate level of resolution for differentiation between strains. However, WGS alone will not be sufficient for tracing and tracking Map infections, yet importantly it can provide a phylogenetic context for affirming epidemiological connections. PMID- 26813575 TI - Interaction of chemokine receptor CXCR4 in monomeric and dimeric state with its endogenous ligand CXCL12: coarse-grained simulations identify differences. AB - Despite the recent resolutions of the crystal structure of the chemokine receptor CXCR4 in complex with small antagonists or viral chemokine, a description at the molecular level of the interactions between the full-length CXCR4 and its endogenous ligand, the chemokine CXCL12, in relationship with the receptor recognition and activation, is not yet completely elucidated. Moreover, since CXCR4 is able to form dimers, the question of whether the CXCR4-CXCL12 complex has a 1:1 or 2:1 preferential stoichiometry is still an open question. We present here results of coarse-grained protein-protein docking and molecular dynamics simulations of CXCL12 in association with CXCR4 in monomeric and dimeric states. Our proposed models for the 1:1 and 2:1 CXCR4-CXCL12 quaternary structures are consistent with recognition and activation motifs of both partners provided by the available site-directed mutagenesis data. Notably, we observed that in the 2:1 complex, the chemokine N-terminus makes more steady contacts with the receptor residues critical for binding and activation than in the 1:1 structure, suggesting that the 2:1 stoichiometry would favor the receptor signaling activity with respect to the 1:1 association. PMID- 26813577 TI - Orientational Imaging of a Single Gold Nanorod at the Liquid/Solid Interface with Polarized Evanescent Field Illumination. AB - Understanding the mechanistic information on many kinetic processes requires the exploration of dynamic rotational information on the target object at the single particle (or molecule) level. In this work, we developed a new strategy, total internal reflection scattering (TIRS) microscopy, to determine the full three dimensional (3D) angular information on a single gold nanorod (GNR) close to the liquid/solid interface. It was found that the 3D orientational information on individual GNR could be readily elucidated by using p-polarized TIRS illumination through deciphering the orientation-coded intensity distribution pattern in a single TIRS image. In comparison with the previously reported strategies, this method does not require complicated focal plane correction, affording a versatile pathway to track the rotational dynamics close to the interface in a high throughput manner. The methodology presented here, therefore, demonstrates a promising approach that can be applied to fluidic membranes, including membranes with polymers, bound proteins, and so on. PMID- 26813576 TI - Selection of suitable reference genes for qRT-PCR normalization during leaf development and hormonal stimuli in tea plant (Camellia sinensis). AB - Tea plant (Camellia sinensis) leaf is an important non-alcoholic beverage resource. The application of quantitative real time polymerase chain reaction (qRT-PCR) has a profound significance for the gene expression studies of tea plant, especially when applied to tea leaf development and metabolism. In this study, nine candidate reference genes (i.e., CsACT7, CsEF-1alpha, CseIF-4alpha, CsGAPDH, CsPP2A, CsSAND, CsTBP, CsTIP41, and CsTUB) of C. sinensis were cloned. The quantitative expression data of these genes were investigated in five tea leaf developmental stages (i.e., 1st, 2nd, 3rd, 4th, and older leaves) and normal growth tea leaves subjected to five hormonal stimuli (i.e., ABA, GA, IAA, MeJA, and SA), and gene expression stability was calculated using three common statistical algorithms, namely, geNorm, NormFinder, and Bestkeeper. Results indicated that CsTBP and CsTIP41 were the most stable genes in tea leaf development and CsTBP was the best gene under hormonal stimuli; by contrast, CsGAPDH and CsTUB genes showed the least stability. The gene expression profile of CsNAM gene was analyzed to confirm the validity of the reference genes in this study. Our data provide basis for the selection of reference genes for future biological research in the leaf development and hormonal stimuli of C. sinensis. PMID- 26813578 TI - Nesterenkonia aurantiaca sp. nov., an alkaliphilic actinobacterium isolated from Antarctica. AB - A Gram-stain-positive, non-endospore-forming, haloalkaliphilic actinobacterium, strain CK5T, was isolated from a soil sample, collected at Cape King (Antarctica), and its taxonomic position was investigated by using a polyphasic approach. Cells were cocci with orange pigmentation, non-motile and grew optimally at 25 degrees C and pH 9.0-9.5 in the presence of 2 % (w/v) NaCl. Cellular membrane contained MK-7 (72 %) and MK-8 (28 %), and anteiso-C15 : 0 (64.8 %), iso-C16 : 0 (13.3 %), n-C17 : 0 (9.9 %), n-C16 : 0 (4.0 %), n-C14 : 0 (3.7 %) as major cellular fatty acids. The DNA G+C content was 64.8 mol%. Strain CK5T, based on the 16S rRNA gene sequence similarity, was most closely related to Nesterenkonia jeotgali JG-241T (99.5 %), Nesterenkonia sandarakina YIM 70009T (99.4 %), Nesterenkonia lutea YIM 70081T (99.4 %), Nesterenkonia halotolerans YIM 70084T (99.3 %), Nesterenkonia xinjiangensis YIM 70097T (97.2 %), Nesterenkonia flava CAAS 251T (97.1 %) and Nesterekonia aethiopica CCUG 48939T (97.1 %). Strain CK5T revealed 31 % DNA-DNA relatedness with respect to N. sandarakina DSM 15664T, 29 % with respect to N. jeotgali DSM 19081T, 10 % with respect to N. lutea DSM 15666T and 1 % with respect to N. halotolerans, DSM 15474T, N. xinjiangensis DSM 15475T, N. aethiopica DSM 17733T and N. flava DSM 19422T. On the basis of 16S rRNA gene sequences, DNA-DNA hybridization and chemotaxonomic characteristics, strain CK5T represents a novel species of the genus Nesterenkonia, for which the name Nesterenkonia aurantiaca sp. nov. is proposed. The type strain is CK5T ( = DSM 27373T = JCM 19723T). PMID- 26813579 TI - Short range smectic order driving long range nematic order: example of cuprates. AB - We present a model for describing the combined presence of nematic and 'smectic' or stripe-like orders seen in recent scanning tunneling microscopy (STM) experiments on cuprates. The smectic order is treated as an electronic charge density wave with an associated Peierls distortion or a 'Pomeranchuk wave'. This primary order is restricted to nanoscale domains by disorder effects, while the secondary coupling to strain generates the nematic order with a considerably longer range. A variety of experimental results are shown to be consistent with our theoretical predictions. PMID- 26813580 TI - Stable solid and aqueous H2CO3 from CO2 and H2O at high pressure and high temperature. AB - Carbonic acid (H2CO3) forms in small amounts when CO2 dissolves in H2O, yet decomposes rapidly under ambient conditions of temperature and pressure. Despite its fleeting existence, H2CO3 plays an important role in the global carbon cycle and in biological carbonate-containing systems. The short lifetime in water and presumed low concentration under all terrestrial conditions has stifled study of this fundamental species. Here, we have examined CO2/H2O mixtures under conditions of high pressure and high temperature to explore the potential for reaction to H2CO3 inside celestial bodies. We present a novel method to prepare solid H2CO3 by heating CO2/H2O mixtures at high pressure with a CO2 laser. Furthermore, we found that, contrary to present understanding, neutral H2CO3 is a significant component in aqueous CO2 solutions above 2.4 GPa and 110 degrees C as identified by IR-absorption and Raman spectroscopy. This is highly significant for speciation of deep C-O-H fluids with potential consequences for fluid carbonate-bearing rock interactions. As conditions inside subduction zones on Earth appear to be most favorable for production of aqueous H2CO3, a role in subduction related phenomena is inferred. PMID- 26813581 TI - Exploring the role of the alpha-carboxyphosphonate moiety in the HIV-RT activity of alpha-carboxy nucleoside phosphonates. AB - As alpha-carboxy nucleoside phosphonates (alpha-CNPs) have demonstrated a novel mode of action of HIV-1 reverse transcriptase inhibition, structurally related derivatives were synthesized, namely the malonate 2, the unsaturated and saturated bisphosphonates 3 and 4, respectively and the amide 5. These compounds were evaluated for inhibition of HIV-1 reverse transcriptase in cell-free assays. The importance of the alpha-carboxy phosphonoacetic acid moiety for achieving reverse transcriptase inhibition, without the need for prior phosphorylation, was confirmed. The malonate derivative 2 was less active by two orders of magnitude than the original alpha-CNPs, while displaying the same pattern of kinetic behavior; interestingly the activity resides in the "L"-enantiomer of 2, as seen with the earlier series of alpha-CNPs. A crystal structure with an RT/DNA complex at 2.95 A resolution revealed the binding of the "L"-enantiomer of 2, at the polymerase active site with a weaker metal ion chelation environment compared to 1a (T-alpha-CNP) which may explain the lower inhibitory activity of 2. PMID- 26813582 TI - Interactions between the Powdery Mildew Effector BEC1054 and Barley Proteins Identify Candidate Host Targets. AB - There are over 500 candidate secreted effector proteins (CSEPs) or Blumeria effector candidates (BECs) specific to the barley powdery mildew pathogen Blumeria graminis f.sp. hordei. The CSEP/BEC proteins are expressed and predicted to be secreted by biotrophic feeding structures called haustoria. Eight BECs are required for the formation of functional haustoria. These include the RNase-like effector BEC1054 (synonym CSEP0064). In order to identify host proteins targeted by BEC1054, recombinant BEC1054 was expressed in E. coli, solubilized, and used in pull-down assays from barley protein extracts. Many putative interactors were identified by LC-MS/MS after subtraction of unspecific binders in negative controls. Therefore, a directed yeast-2-hybrid assay, developed to measure the effectiveness of the interactions in yeast, was used to validate putative interactors. We conclude that BEC1054 may target several host proteins, including a glutathione-S-transferase, a malate dehydrogenase, and a pathogen-related-5 protein isoform, indicating a possible role for BEC1054 in compromising well known key players of defense and response to pathogens. In addition, BEC1054 interacts with an elongation factor 1 gamma. This study already suggests that BEC1054 plays a central role in barley powdery mildew virulence by acting at several levels. PMID- 26813583 TI - Capturing Transient Endoperoxide in the Singlet Oxygen Oxidation of Guanine. AB - The chemistry of singlet O2 toward the guanine base of DNA is highly relevant to DNA lesion, mutation, cell death, and pathological conditions. This oxidative damage is initiated by the formation of a transient endoperoxide through the Diels-Alder cycloaddition of singlet O2 to the guanine imidazole ring. However, no endoperoxide formation was directly detected in native guanine or guanosine, even at -100 degrees C. Herein, gas-phase ion-molecule scattering mass spectrometry was utilized to capture unstable endoperoxides in the collisions of hydrated guanine ions (protonated or deprotonated) with singlet O2 at ambient temperature. Corroborated by results from potential energy surface exploration, kinetic modeling, and dynamics simulations, various aspects of endoperoxide formation and transformation (including its dependence on guanine ionization and hydration states, as well as on collision energy) were determined. This work has pieced together reaction mechanisms, kinetics, and dynamics data concerning the early stage of singlet O2 induced guanine oxidation, which is missing from conventional condensed-phase studies. PMID- 26813584 TI - Structure and electrochemical properties for complexes of nitrocompounds with inorganic ions: A theoretical approach. AB - Reduction and oxidation (redox) reactions are widely used for removal of nitrocompounds from contaminated soil and water. Structures and redox properties for complexes of nitrocompounds, such as 2,4,6-trinitrotoluene (TNT), 2,4 dinitrotoluene (DNT), 2,4-dinitroanisole (DNAN), and 5-nitro-2,4-dihydro-3H-1,2,4 triazol-3-one (NTO), with common inorganic ions (Na(+) , Cl(-) , NO3-) were investigated at the SMD(Pauling)/PCM(Pauling)/MPWB1K/TZVP level of theory. Atoms in molecules (AIM) theory was applied to analyze the topological properties of the bond critical points involved in the interactions between the nitrocompounds and the ions. Topological analyses show that intermolecular interactions of the types O(N)...Na(+) , C-H...Cl(-) ( ONO2-), and C...Cl(-) ( ONO2-) may be discussed as noncovalent closed-shell interactions, while N-H...Cl(-) ( ONO2-) hydrogen bonds are partially covalent in nature. Complexation causes significant decrease of redox activity of the nitrocompounds. Analysis of the reduction potentials of the complexes obtained through application of the Pourbaix diagram of an iron/water system revealed that sodium complexes of NTO might be reduced by metallic iron. (c) 2016 Wiley Periodicals, Inc. PMID- 26813585 TI - Nutrition and neurodevelopmental outcomes in preterm infants: a systematic review. AB - A systematic review with meta-analysis was carried out to investigate the effects of increased nutritional intake, via either macronutrient or multinutrient intervention, during the neonatal period on neurodevelopmental outcomes in infants born at <32 weeks of gestation or weighing <1501 g at birth. CONCLUSION: Although the relationship remains unclear, increased early nutrition may reduce neurodevelopmental impairment in this group of infants. Future research should focus on using standardised nutritional interventions and an agreed neurodevelopmental assessment battery. PMID- 26813586 TI - Ultrahigh Mobility in an Organic Semiconductor by Vertical Chain Alignment. AB - A method to produce highly efficient and long-range vertical charge transport is demonstrated in an undoped polythiophene thin film, with average mobilities above 3.1 cm(2) V(-1) s(-1) . These record high mobilities are achieved by controlled orientation of the polymer crystallites enabling the most efficient and fastest charge transport along the chain backbones and across multiple chains. The significant increase in mobility shown here may present a new route to producing faster and more efficient optoelectronic devices based on organic materials. PMID- 26813588 TI - [Treatment options in the elderly patients with advanced non-small-cell lung cancer]. PMID- 26813587 TI - Regulation of human cerebro-microvascular endothelial baso-lateral adhesion and barrier function by S1P through dual involvement of S1P1 and S1P2 receptors. AB - Herein we show that S1P rapidly and acutely reduces the focal adhesion strength and barrier tightness of brain endothelial cells. xCELLigence biosensor technology was used to measure focal adhesion, which was reduced by S1P acutely and this response was mediated through both S1P1 and S1P2 receptors. S1P increased secretion of several pro-inflammatory mediators from brain endothelial cells. However, the magnitude of this response was small in comparison to that mediated by TNFalpha or IL-1beta. Furthermore, S1P did not significantly increase cell-surface expression of any key cell adhesion molecules involved in leukocyte recruitment, included ICAM-1 and VCAM-1. Finally, we reveal that S1P acutely and dynamically regulates microvascular endothelial barrier tightness in a manner consistent with regulated rapid opening followed by closing and strengthening of the barrier. We hypothesise that the role of the S1P receptors in this process is not to cause barrier dysfunction, but is related to controlled opening of the endothelial junctions. This was revealed using real-time measurement of barrier integrity using ECIS ZTheta TEER technology and endothelial viability using xCELLigence technology. Finally, we show that these responses do not occur simply though the pharmacology of a single S1P receptor but involves coordinated action of S1P1 and S1P2 receptors. PMID- 26813589 TI - [Effect of antibacterial peptide hCAP18/LL-37 on ovarian cancer microenvironment and the regulatory mechanism of its expression]. AB - OBJECTIVE: To investigate the effect of antibacterial peptide hCAP18/LL-37 on ovarian cancer microenvironment and the regulatory mechanism of its expression. METHODS: We assessed the effect of macrophage-promoted ovarian cancer cells invasion using BioCoat Matrigel invasion chamber. The expressions of hCAP18/LL-37 and versican V1 were determined by real-time PCR and Western blot analysis. SKOV3 cells were transfected with shRNA plasmid to abrogate the expression of versican V1, and then the expression of hCAP18/LL-37 in macrophages and the invasiveness of SKOV3 cells were assayed. RESULTS: The Matrigel invasion assay showed that after co-culture with macrophages for 4 days, the number of penetrated SKOV3 cells was 112.8+/-17.1/per high power field, significantly higher than that in the SKOV3 cells cultured alone (8.2+/-1.9/per high power field) (P<0.05). Addition of hCAP/LL-37 neutralizing antibody into the co-cultured macrophage SKOV3 cells markedly inhibited the macrophage-promoted SKOV3 cells invasion. The penetrated SKOV3 cells was 22.2+/-5.6/per high power field, significantly lower than the 100.6+/-25.2/per high power field in the control macrophage- SKOV3 co cultured cells (P<0.05). The expressions of hCAP18/LL-37 mRNA and protein in macrophages were remarkably enhanced upon co-culture with SKOV3 cells, but not changed in SKOV3 cells cultured alone. The expression and secretion of versican V1 in the ovarian cancer cells were also significantly increased after co cultured with macrophages. Knockdown of versican V1 in SKOV3 cells by small interfering RNA significantly reduced the expression of hCAP18/LL-37 mRNA and protein in the macrophages, as well as decreased the invasiveness of SKOV3 cells (P<0.05). CONCLUSIONS: In the cancer microenvironment, the macrophage-secreted hCAP18/LL-37 promote the invasiveness of ovarian cancer cells, and the hCAP18/LL 37 expression is regulated by versican V1 protein released by ovarian cancer cells. PMID- 26813590 TI - [Reversal of stemness in multidrug-resistant hepatocellular carcinoma cells by SIS3]. AB - OBJECTIVE: To investigate whether SIS3, a specific inhibitor of Smad3 phosphorylation, can reverse the stemness of multidrug-resistant(MDR) hepatocellular carcinoma cells. METHODS: MDR HCC Huh7.5.1/ADM cell lines were developed by exposing parental cells to stepwise increasing concentrations of ADM. CCK-8 assay was used to determine the cellular sensitivity of various anticancer drugs. Flow cytometry (FCM) was used to analyze the expression level of cancer stem cell marker CD133. Clone formation assay and mouse subcutaneous xenograft tumors were used to investigate the tumorigenicity in vitro and in vivo. Western blotting (WB) was used to analyze the changes of expressions of CD133, Smad3, Bcl-2, Bax and p-Smad3 in different conditions. RESULTS: ADM treatment of HCC cells in vitro resulted in a development of subline, Huh7.5.1/ADM cells, with CSC phenotypes: stable MDR phenotype (besides ADMc Huh7.5.1/ADM cells were also more resistant to some other anticancer drugs including VCR, MMC and CTX ) (IC50: 0.215 +/- 0.018 vs. 0.123 +/- 0.004, 0.145 +/ 0.009 vs. 0.014 +/- 0.002, 1.021 +/- 0.119 vs. 0.071 +/- 0.006, 27.007 +/- 1.606 vs. 1.919 +/- 0.032) (unit: ug/ml) (P<0.05). Huh7.5.1/ADM cells enriched the cancer stem-like cell fraction (CD133-positive subpopulation) (76.06 +/- 2.948% vs. 25.38 +/- 4.349%) (P<0.05), had stronger tumorigenicity in vivo and colony formation ability, and activated the Smad3 activity. Inhibition of Smad3 activity by SIS3 decreased stemness of the Huh7.5.1/ADM cells: CD133-positive subpopulation (48.49 +/- 2.304% vs. 76.06 +/- 2.948%) (P<0.05); ADM IC50: (0.112 +/- 0.019 vs. 0.215 +/- 0.018), VCR IC50 (0.065 +/- 0.013 vs. 0.145+/-0.009), MMC IC50 (0.749 +/- 0.121 vs. 1.021 +/- 0.119), CTX IC50 (10.576 +/- 1.248 vs. 27.007 +/- 1.606) (unit: ug/ml) (P<0.05), and decreased tumorigenicity and colony formation ability. CONCLUSION: SIS3 as a specific inhibitor of Smad3 signal is involved in the stemness of multidrug resistant hepatocellular carcinoma cells. PMID- 26813591 TI - [Non-small cell lung cancer 95D cells co-cultured with 3D-bioprinted scaffold to construct a lung cancer model in vitro]. AB - OBJECTIVE: To fabricate an innovative scaffold for lung cancer cell culture and establish a three-dimensional lung cancer model in vitro, and to reveal the differences in biological functions of lung cancer cells under the two dimensional and three-dimensional culture conditions. METHODS: We chose agarose and alginate as the scaffold materials, and 3D printing technique was applied to construct cell culture scaffold. 95D cells were co-cultured with this scaffold. The differences of cell morphology, proliferation ability, protein expression, etc. in the cells cultured under 2D and 3D cultural conditions were evaluated by light microscopy using HE staining, MTT assay, scanning electron microscopy, and Western blot analysis. RESULTS: Cells cultured in 2D wells displayed a spindle and polygonal morphology, whereas those grown in the 3D culture aggregated into spheroids, which invaded, migrated and disseminated into the surrounding scaffold. MTT assay showed that the proliferation rates of the 3D-cultured cells for 2-6 days were significantly lower than, but those cultured for 8-9 days were significantly higher than that of the 2D-cultured cells, indicating that proliferative activity of the cells grown in 2D cultures for 8-9 days was inhibited. In contrast, cells grown on 3D scaffolds still maintained a higher proliferation. The Western blot assay showed that the expression of Cdc42, p53, mTOR were significantly down-regulated in 3D scaffold-cultured group (0.529+/ 0.103, 0.820+/-0.038 vs. 1.967+/-0.066), compared with that of the 2D-cultured group (3.063+/-0.139, 1.738+/-0.122 vs. 2.472+/-0.151) (P<0.05 for all), while the expression of MMP-2 was up-regulated in the 3D-cultured cells (1.110+/ 0.029), significantly higher than that of the 2D-cultured cells (0.017+/-0.001) (P<0.05). CONCLUSIONS: The cell morphology, proliferation and associated protein expression of lung cancer cells in 3D-culture systems are distinctively different as compared to those of the 2D-cultural cells. 3D-bioprinted agarose-alginate scaffold can better mimic the growth microenvironment of lung cancer in vivo and may provide a promising model for lung cancer research in vitro. PMID- 26813592 TI - [A standardized protocol for detection of ALK protein expression and gene fusion in lung adenocarcinoma cytologic specimens]. AB - OBJECTIVE: The aim of this study was to establish a standardized protocol for detection of ALK protein expression and gene fusion in cytologic specimens. METHODS: Lung adenocarcinoma cytologic specimens were collected from seven hospitals in Beijing city. A detection protocol for ALK protein expression and gene fusion was designed according to the results of comparative experiment. Ventana immunohistochemical (IHC) ALK(D5F3) detecting ALK protein expression was performed in 203 prepared formalin-fixed paraffin-embedded (FFPE) cell blocks. ALK gene fusion in 98 EGFR gene wild type cytologic specimens and in 4 bronchoalveolar lavage fluid (BL) samples was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). ALK gene fusion in the Ventana IHC ALK (D5F3) positive samples was further tested by fluorescence in situ hybridization (FISH). Six patients with ALK IHC-positive result were followed up to analyze the responses of crizotinib therapy. Comparative experiments: (1) Comparison of the results of 4% neutral buffered formalin fixed for different time (24 h, 48 h, 72 h) on the Ventana IHC ALK (D5F3) staining was conducted in two cases of IHC ALK positive FFPE cell blocks; (2) Comparing qRT-PCR results for ALK fusion in samples from FFPE cell blocks and cytospin prepared slides in 10 cases of lung adenocarcinoma cytologic specimens. RESULTS: Among the specimens examined using the standardized protocol recommended by this study, 229 cases of cytologic specimens met the diagnostic criteria of lung adenocarcinoma. Among them, 207 cases obtained ALK gene test results (by at least one method), with an ALK test ratio of 90.4% (207/229). FFPE cell blocks were successfully prepared in 203 cases, Ventana IHC ALK (D5F3) were successfully performed in all the 203 FFPE cell blocks (100%), and the ALK protein positive detection rate was 10.3% (21/203). ALK fusion was tested in 98 FFPE cytologic samples of EGFR wild types by qRT-PCR, and 96 out of 98 (97.96%) cytologic samples were successfully performed.18 out of 19 IHC ALK-positive cases were verified to be of ALK fusion status by qRT-PCR. The concordance rate was 94.7% (Kappa=0.967, P<0.001) between Ventana IHC ALK (D5F3) and qRT-PCR, and the sensitivity of the Ventana IHC ALK (D5F3) assay compared with qRT-PCR was 100% and the specificity was 98.7%. FISH assay was used to verify the positive cases detected by Ventana IHC ALK (D5F3) staining. Two cases of low tumor cell content FFPE samples obtained indefinite results by FISH test. The six patients with positive ALK protein expression received crizotinib therapy, and 5 paitents got treated effectively. For two ALK IHC positive cases, which were 4% neutral buffered formalin fixed for 72 h, the result of Ventana IHC ALK (D5F3) staining became weakened obviously and uneven. In 10 cases of samples, total RNA was extracted from FFPE cytologic sections and cytospin prepared slides, and the results of qRT-PCR test and ALK gene fusion showed good concordance. CONCLUSIONS: The standardized protocol recommended in this study expands the detection types and quantity of cytologic specimens for ALK protein expression and gene fusion and increased the detection rate. Ventana IHC ALK (D5F3) is a reliable method for detecting ALK protein expression in FFPE cell blocks. The pathologic quality control procedure prior to Ventana IHC ALK (D5F3) is crucial for the accuracy of testing the ALK gene status. When FFPE cell blocks could not be prepared or prepared unsuccessfully from the cytologic specimens, qRT-PCR may be an alternative option for the detection of ALK gene fusion. PMID- 26813593 TI - [Value of CK5/6, CK14, ER and PR detection in differential diagnosis of intraductal proliferative lesions of the breast]. AB - OBJECTIVE: To investigate the expression of high-molecular-weight keratins CK5/6, CK14, estrogen receptor (ER) and progesterone receptor (PR) in differential diagnosis of simple ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH) and low-grade ductal carcinoma in situ (low-grade DCIS) . METHODS: The clinicopathological data of twenty cases of atypical ductal epithelial hyperplasia (ADH) with focal cancerization changed into low-grade DCIS diagnosed at Tianjin Medical University Cancer Institute and Hospital between January 2013 and February 2014 were reviewed and analyzed. The expressions of CK5/6, CK14, ER and PR were detected by immunohistochemistry. RESULTS: Positive expressions of CK5/6 and CK14 were seen in UDH showing a mosaic pattern, while negative expression in ADH and low-grade DCIS. In addition, CK5/6 and CK14 were positively expressed in the myoepithelial cells of UDH, ADH and low-grade DCIS. Positive expressions of ER and PR were observed in UDH, ADH and low-grade DCIS. But they presented diffuse and homogeneous strong positive expression in ADH and variable positive expression in UDH. CONCLUSION: In the intraductal proliferative lesions of the breast, the use of combined detection of the expression of CK5/6, CK14, ER and PR is of practical significance in the differential diagnosis of UDH, ADH and low-grade DCIS. PMID- 26813594 TI - [Value of E-PASS and mE-PASS in predicting morbidity and mortality of gastric cancer surgery]. AB - OBJECTIVE: To investigate the clinical value of Physiologic Ability and Surgical Stress (E-PASS) and modified Estimation of Physiologic Ability and Surgical Stress (mE-PASS) scoring systems in predicting the mortality and surgical risk of gastric cancer patients, and to analyze the relationship between the parameters of E-PASS and early postoperative complications. METHODS: Clinical data of 778 gastric cancer patients who underwent elective surgical resection in Tianjin Medical University General Hospital from Jan. 2010 to Jan. 2014 were analyzed retrospectively. E-PASS and mE-PASS scoring systems were used to predict the mortality of gastric cancer patients, respectively. Univariate and unconditioned logistic regression analyses were performed to assess the relationships between nine parameters of E-PASS system and early postoperative complications. RESULTS: E-PASS and mE-PASS systems were used to predict the mortality in the death group and non-death group. The Z value was -5.067 and -4.492, respectively, showing a significant difference between the two groups (P<0.05). AUCs of mortality predicted by E-PASS and mE-PASS were 0.926 and 0.878 (P>0.05), and the prediction calibration of postoperative mortality showed statistically non-significant difference (P>0.05) between the E-PASS and mE-PASS prediction and actual mortality. Univariate analysis showed that age, operation time, severe heart disease, severe lung disease, diabetes mellitus, physical state index and ASA classification score are related to postoperative complications (P<0.05 for all). Unconditioned logistic regression analysis showed that severe lung disease, diabetes mellitus, ASA classification score and operation time are risk factors for early postoperative complications (P<0.05 for all). CONCLUSIONS: Both mE-PASS and E-PASS scoring system have good consistency in the predicting postoperative mortality and actual mortality, and both are suitable for clinical application. Moreover, the mE-PASS scoring system is clinically more simple and convenient than E-PASS scoring system. Preoperative severe lung disease, diabetes mellitus, ASA classification score and operation time are independent factors affecting the early postoperative complications. PMID- 26813595 TI - [Target-resequencing to identify microRNA-associated SNP and predict the effect of SNP on microRNA function in colorectal cancer patients]. AB - OBJECTIVE: To identify SNPs in the miRNA genes in colorectal cancer (CRC) patients and to investigate their association with CRC. METHODS: DNAs were isolated from 30 CRC tumor tissues and 30 tumor-adjacent tissues, and subjected to target capture using a custom miRNA chip covering 685 miRNA genes from NimbleGen. The captured DNAs were then sequenced using the Illumina's sequencing technology, and the data were analyzed. RESULTS: We identified 64 SNPs in 43 miRNA genes and most of these SNPs are novel SNPs not reported previously. Prediction of functional consequences of the SNPs using TargetScan and miRSNP showed that SNPs of hsa-mir-1273-G/A, hsa-mir-548h-3-C/U, hsa-mir-1290-A/G, and hsa-mir-1273-C/U resulted in reduction of their mature miRNA abundance. SNPs of hsa-mir-376b-C/G, hsa-mir-604-T/C, hsa-mir-1268-T/G and hsa-mir-146a-C/G resulted in changes in their targeted genes. Finally, we focused on the analysis of SNPs in mir-146a and we found that mir-146a rs1052918 C>G was predicted to promote tumorigenesis via the Wnt signaling pathway. CONCLUSIONS: SNPs in the miRNA genes are important for tumorigenesis. The changes by hsa-mir-146a rs1052918 C>G may result in loss of Wnt, constant activation of the Wnt signaling pathway, and uncontrolled cell proliferation and tumor progression. PMID- 26813596 TI - [Expression and clinical significance of GRHL2 in colorectal cancer]. AB - OBJECTIVE: The purpose of this study was to detect the expression of GRHL2 in colorectal cancer (CRC) tissues, and to assess the relationship between GRHL2 expression and clinicopathological features. METHODS: Immunohistochemistry was used to examine GRHL2 in 75 CRC tissues. GRHL2 mRNA and protein levels in the CRC tissues were also analyzed by qRT-PCR and Western blot. The relationship between GRHL2 and clinicopathological features was assessed by Pearson's chi-square (chi(2)) test. RESULTS: Positive immunoreactivity for GRHL2 was detected in the nuclei of CRC cells. GRHL2 expression was increased in CRC tissues compared withthat in the paired non-tumor tissues (61.3% vs. 44.0%, P<0.01). Moreover, qRT PCR results showed that the relative expression level of GRHL2 mRNA in the colorectal cancer tissue was (2.64+/-0.35), significantly higher than that of normal mucosa tissue (1.19+/-0.23, P<0.001). The expression level of GRHL2 mRNA was higher in stage III-IV patients (2.84+/-0.36) than that of stage I-II cases (2.31+/-0.32, P<0.05). Western blot results also showed that the expression level of GRHL2 protein in the colorectal carcinoma tissue was significantly higher than that in the normal mucosa (P<0.05). GRHL2 expression was positively correlated with tumor size, TNM stage and Ki-67 (P<0.05, respectively). CONCLUSION: Taking together, our findings demonstrate that GRHL2 is overexpressed in CRC, and plays an important role in the progression of CRC. PMID- 26813597 TI - [Reliability and validity of the FACIT-AI Chinese-version for assessing quality of life in patients with malignant ascites]. PMID- 26813598 TI - [Analysis of the patterns of cervical lymph node recurrence in patients with cN0 papillary thyroid carcinoma after central neck lymph node dissection]. AB - OBJECTIVE: To retrospectively analyze the long-term results of prophylactic central lymph node dissection in cN0 papillary thyroid carcinoma (PTC), and investigate the treatment method of the cervical lymph nodes for cN0 PTC. METHODS: One hundred and thirty-six patients with cN0 PTC were treated by surgery at the Cancer Hospital of Chinese Academy of Medical Sciences from 2000 to 2006. Their clinicopathological characteristics, surgical procedures and survival outcomes were collected and analyzed. RESULTS: The occult lymph node metastasis rate in central compartment was 61.0%. The average number of positive lymph nodes was 2.47 (1-13), in which 54 patients had 1-2 and 29 patients had >= 3 positive lymph nodes. Multiple logistic regression analysis showed that age less than 45 (P=0.001, OR 3.571, 95% CI 1.681-7.587)and extracapsular spread (ECS) (P=0.015, OR 2.99, 95% CI 1.241-7.202)were independent risk factors for lymph node metastasis in the central compartment. The ten-year cumulative overall survival rate was 98.3% and cumulative lateral neck metastasis rate was 25.2%. Multivariate analysis with Cox regression model showed that ECS (P=0.001, OR 5.211, 95% CI1.884-14.411) and positive lymph nodes in the central compartment >= 3 (P=0.009, OR 4.005, 95% CI 1.419-11.307) were independent risk factors for lymph node recurrence in the lateral neck region. The distribution of recurrent lymph nodes: level IV (82.4%), level III (64.7%), level II (29.4%) and level V (11.8%). CONCLUSIONS: Routine central lymph node dissection, at least unilateral, should be conducted for cN0 papillary thyroid carcinoma. Attention should be paid to the treatment of lateral neck region in patients with cN0 papillary thyroid carcinoma. Selective neck dissection is suggested for cN0 PTC with ECS or positive central lymph nodes >= 3, or both. The range of dissection should include level III and IV at least. PMID- 26813599 TI - [Analysis of the effectiveness of radiotherapy in postoperative residual tumors in patients with thyroid papillary carcinoma]. AB - OBJECTIVE: The aim of this study was to assess the impact of radiotherapy on patients with postoperative residual or recurrent papillary thyroid cancer (PTC). METHODS: We retrospectively reviewed the medical records of 34 patients with PTC, who underwent surgery and radiotherapy in other hospitals, and treated at the Department of Head and Neck Surgery at Cancer Institute & Hospital CAMS from January 2011 to January 2014. Among the 34 cases, 22 were in stage I, 5 in stage II and 7 in stage IVa. The 34 patients received 1.5 times of surgery before radiotherapy in average. All the cases received radiotherapy (mean, 56 Gy; range, 50-70 Gy). The patients were re-operated in our hospital, and the specimens were examined by pathology. The pre- and post-radiotherapy images (CT and B ultrasound) were compared, and the changes of tumor volume were examined. The objective effect of treatment on the tumor residual focus was evaluated using RECIST, and analyzed by t-test (SPSS 17.0). RESULTS: All the re-resected lesions after radiotherapy were proved by pathology to be papillary thyroid cancer (PTC) or metastatic PTC in cervical lymph nodes. Among the 34 patients, 22 cases showed mild or moderate cell degeneration and the other 12 cases showed no obvious degeneration. The largest tumor diameter was 27.18 mm before radiotherapy and 27.76 mm after radiotherapy, with a non-significant difference between them (t= 1.618, P>0.05). Among the 34 patients, only 3 patients received reoperation, all other 31 cases had complete resection, and no severe complications were observed except recurrent laryngeal nerve injury in one case. CONCLUSIONS: Radiotherapy has few therapeutic benefit to PTC patients after surgery with residual tumor or local recurrence. It should be used in the PTC patients, in which the tumor invasion involves important organ tissues and is difficult for a single operation to achieve safe resection margin, or in patients who can't bear a surgery because of severe coronary heart disease or others. PMID- 26813600 TI - [Prognostic impact of different chemotherapy strategies on small cell esophageal carcinoma]. AB - OBJECTIVE: To investigate the prognostic impact of different chemotherapy strategies on small cell esophageal carcinoma (SCEC). METHODS: The clinical data of 62 patients with histologically confirmed SCEC treated in our department between January 2006 and April 2011 were retrospectively analyzed. There were 39 patients with limited stage (LS) and 23 patients with extensive stage (ES) SCEC according to the Veterans Administration Lung Study Group staging system. Cox's hazard regression model was used to determine the prognostic factors, and Chi square test was used to detect the difference of frequencies among different groups. Kaplan-Meier and log-rank analyses were used to estimate and compare the survival rates. RESULTS: The chemotherapy combined with local therapy group was significantly better than chemotherapy alone group in median survival time (MST) (20.8 vs. 7.6 months, P<0.05). The MST was 18.0 months and the 1-, 2-, and 3-year overall survival rates (OS) were 68.8%, 38.6%, and 20.9%, respectively, for all the 62 patients. Etoposide plus cisplatin or carboplatin (EP/CP) did not result in significantly longer MST, compared with that of the cases treated by other combination chemotherapy (P>0.05, for either LS or ES cases). Multivariate analysis showed that the VALSG stage, the number of chemotherapy cycles (>= 4), and treatment modality are independent prognostic factors (P<0.05). CONCLUSIONS: SCEC is a tumor characterized by high malignancy and poor prognosis. Chemotherapy combined with local therapy is an effective treatment for SCEC, and appropriate chemotherapy cycles (>= 4) may improve the survival time. EP/CP, as commonly used multidrug chemotherapy regimen, is not superior to other combination chemotherapy. PMID- 26813601 TI - [Efficacy of crizotinib for 28 cases of advanced ALK-positive non-small cell lung cancer]. AB - OBJECTIVE: This study aims to evaluate the efficacy and safety of crizotinib for advanced ALK-positive non-small cell lung cancer (NSCLC) patients. METHODS: Twenty-eight patients with advanced ALK-positive NSCLC were given orally crizotinib 250 mg b. i.d., and were followed up to evaluate the therapeutic efficacy and safety. RESULTS: Among the 28 patients, the objective response rate (ORR) was 71.4% (20/28) and disease control rate (DCR) was 92.9% (26/28). Three patients achieved complete response. Seventeen patients had partial response. The most common drug-related adverse events were mild flickering vision and gastrointestinal reaction. Eleven patients experienced flickering vision. Nine patients had nausea and vomiting. Eight patients had diarrhea. They were all reversible and of grade I or II. Only one patient had grade III myelosuppression. Among the 28 patients, 16 cases were disease-free and 12 cases had progressive disease, with a progression-free survival of 8.2 months. CONCLUSIONS: Crizotinib is effective and tolerable in the treatment of advanced ALK-positive NSLCC. However, its long-term treatment efficacy requires to be further studied. PMID- 26813602 TI - [Efficacy and toxicity of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes]. AB - OBJECTIVE: To assess the efficacy of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes. METHODS: Clinical data of 48 patients diagnosed and treated for mTNBC between 2004 and 2012 at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) were retrospectively analyzed. All patients were pretreated with anthracyclines and at least one taxane in neo-adjuvant, adjuvant or chemotherapy for mTNBC and patients should be having at least one measurable metastatic lesion. Totally, 48 patients were included in this study, of which 21 cases received first-line chemotherapy and 27 cases received second-line chemotherapy. Based on the regimen they received, 22 patients were treated with NVB plus platinum (NP), and 26 patients with NVB plus capecitabine (NX). RESULTS: After 70 months follow-up, in the total group of patients, the objective response rate was 20.8%, clinical benefit rate was 43.8%, median progression free survival (PFS) was 4.4 months and median overall survival (OS) was 15.5 months. In addition, the ORR was significantly better in the NP arm versus NX arm (33.8% vs.7.7%, P=0.029) as well as PFS was statistically improved in the NP arm than NX arm (5.3 m vs. 3.0 m, P=0.023). Similar trend was observed in the OS, although the difference was not statistically significant (27.7 m vs. 14.8 m, P=0.077). In all, the most frequently reported adverse events were G1/2 gastrointestinal toxicity (68.8%) and neutropenia (62.5%) . No significant difference was observed between the NP arm and NX arm (P>0.05). The percentage of patients who delayed chemotherapy administration in the NP arm and NX arm was 9.1% (n=2), and 3.8% (n=1), respectively. CONCLUSIONS: NVB-based combination chemotherapy demonstrates moderate efficacy in mTNBC patients pretreated with anthracyclines and one taxane with manageable toxicity. NP regimen shows potential superiority over NX regimen, and should be further verified in randomized phase III clinical trial in larger cohort. PMID- 26813603 TI - [Learning curve for middle pancreatectomy]. AB - OBJECTIVE: To explore the learning curve for middle pancreatectomy by comparing the outcomes of middle pancreatectomy operated by a single treatment group at different stages. METHODS: A total of 48 patients received middle pancreatectomy by single treatment group between January 2006 and April 2014 at our hospital. These 48 cases were divided into 10 stages (5 cases in each) according to the operation sequence. The operation time, blood loss, surgical complications, rate of negative margin and postoperative hospital stay were analyzed retrospectively. RESULTS: There was no significant difference among the 10 stages in respect to surgical complications, rate of negative margin and postoperative hospital stay (P>0.05). The median operation time and blood loss in the first stage was 375 min and 530 ml, respectively. The median operation time and blood loss in the second stage was 280 min and 330 ml, respectively. There were significant differences between these two stages and the other later stages in median operation time and blood loss (P<0.01). However, there was no significant difference among the stages 3 to 10 in the median operation time and blood loss (P>0.05 for all). CONCLUSION: After 10-15 cases of middle pancreatectomy, a surgeon can be skilled and experienced in this surgical procedure with few surgical complications. PMID- 26813604 TI - [The Guideline for Diagnosis and Treatment of Chinese Patients with sensitizing EGFR Mutation or ALK Fusion Gene-Positive Non-Small Cell Lung Cancer (2015 Version)]. PMID- 26813605 TI - Misorientation-angle-dependent electrical transport across molybdenum disulfide grain boundaries. AB - Grain boundaries in monolayer transition metal dichalcogenides have unique atomic defect structures and band dispersion relations that depend on the inter-domain misorientation angle. Here, we explore misorientation angle-dependent electrical transport at grain boundaries in monolayer MoS2 by correlating the atomic defect structures of measured devices analysed with transmission electron microscopy and first-principles calculations. Transmission electron microscopy indicates that grain boundaries are primarily composed of 5-7 dislocation cores with periodicity and additional complex defects formed at high angles, obeying the classical low angle theory for angles <22 degrees . The inter-domain mobility is minimized for angles <9 degrees and increases nonlinearly by two orders of magnitude before saturating at ~ 16 cm(2) V(-1) s(-1) around misorientation angle ~ 20 degrees . This trend is explained via grain-boundary electrostatic barriers estimated from density functional calculations and experimental tunnelling barrier heights, which are ~ 0.5 eV at low angles and ~ 0.15 eV at high angles (>= 20 degrees ). PMID- 26813607 TI - Abnormal Chest Radiograph Due to a Common Lung Finding in Down Syndrome. PMID- 26813606 TI - Col4a1 mutations cause progressive retinal neovascular defects and retinopathy. AB - Mutations in collagen, type IV, alpha 1 (COL4A1), a major component of basement membranes, cause multisystem disorders in humans and mice. In the eye, these include anterior segment dysgenesis, optic nerve hypoplasia and retinal vascular tortuosity. Here we investigate the retinal pathology in mice carrying dominant negative Col4a1 mutations. To this end, we examined retinas longitudinally in vivo using fluorescein angiography, funduscopy and optical coherence tomography. We assessed retinal function by electroretinography and studied the retinal ultrastructural pathology. Retinal examinations revealed serous chorioretinopathy, retinal hemorrhages, fibrosis or signs of pathogenic angiogenesis with chorioretinal anastomosis in up to approximately 90% of Col4a1 mutant eyes depending on age and the specific mutation. To identify the cell-type responsible for pathogenesis we generated a conditional Col4a1 mutation and determined that primary vascular defects underlie Col4a1-associated retinopathy. We also found focal activation of Muller cells and increased expression of pro angiogenic factors in retinas from Col4a1(+/Deltaex41)mice. Together, our findings suggest that patients with COL4A1 and COL4A2 mutations may be at elevated risk of retinal hemorrhages and that retinal examinations may be useful for identifying patients with COL4A1 and COL4A2 mutations who are also at elevated risk of hemorrhagic strokes. PMID- 26813609 TI - Risk factors of vitamin D deficiency in children with epilepsy taking anticonvulsants at initial and during follow-up. AB - PURPOSE: Vitamin D status was evaluated in children with epilepsy taking anticonvulsants to determine the prevalence and risk factors of vitamin D deficiency. METHODS: This study was designed as both a cross-sectional and a retrospective cohort study. A sum of 198 children who were diagnosed with epilepsy at the Department of Pediatrics in Dankook University Hospital was included. Their serum vitamin D levels were reviewed based on clinical information, and analyzed using IBM SPSS ver. 20.0. RESULTS: One hundred twenty four children (62.6%) had vitamin D deficiency. Two risk factors were associated: winter to spring season (odds ratio [OR], 3.71; 95% confidence interval [CI], 1.835-7.492) and age more than 12 years (OR, 3.22; 95% CI, 1.377-7.542). Out of the 57 patients who were not vitamin D deficient at the time of initial assay, 47 patients (82.5%) became vitamin D deficient during followup. The change of serum 25-hydroxy vitamin D3 (25(OH)D) levels during follow up showed a weak negative correlation with the duration of medication (r=-0.283, P=0.033). Medication duration was longer and brain magnetic resonance imaging (MRI) abnormality, abnormal underlying conditions, and nonambulatory status were more frequently present in twenty-five patients (44%) who showed a decline of more than 15 ng/mL during follow-up (P<0.05). CONCLUSION: Vitamin D deficiency is common in children with epilepsy taking anticonvulsants, especially in adolescents more than 12 years of age. This study emphasizes the regular monitoring of vitamin D level, especially in the presence of longer duration of medication, brain MRI abnormality, abnormal underlying conditions, and nonambulatory status. PMID- 26813610 TI - The JAK2 V617F Mutation in Plasma Cell Neoplasms with Co-existing Erythrocytosis. PMID- 26813608 TI - Competence of Thiamin Diphosphate-Dependent Enzymes with 2'-Methoxythiamin Diphosphate Derived from Bacimethrin, a Naturally Occurring Thiamin Anti-vitamin. AB - Bacimethrin (4-amino-5-hydroxymethyl-2-methoxypyrimidine), a natural product isolated from some bacteria, has been implicated as an inhibitor of bacterial and yeast growth, as well as in inhibition of thiamin biosynthesis. Given that thiamin biosynthetic enzymes could convert bacimethrin to 2'-methoxythiamin diphosphate (MeOThDP), it is important to evaluate the effect of this coenzyme analogue on thiamin diphosphate (ThDP)-dependent enzymes. The potential functions of MeOThDP were explored on five ThDP-dependent enzymes: the human and Escherichia coli pyruvate dehydrogenase complexes (PDHc-h and PDHc-ec, respectively), the E. coli 1-deoxy-D-xylulose 5-phosphate synthase (DXPS), and the human and E. coli 2-oxoglutarate dehydrogenase complexes (OGDHc-h and OGDHc ec, respectively). Using several mechanistic tools (fluorescence, circular dichroism, kinetics, and mass spectrometry), it was demonstrated that MeOThDP binds in the active centers of ThDP-dependent enzymes, however, with a binding mode different from that of ThDP. While modest activities resulted from addition of MeOThDP to E. coli PDHc (6-11%) and DXPS (9-14%), suggesting that MeOThDP derived covalent intermediates are converted to the corresponding products (albeit with rates slower than that with ThDP), remarkably strong activity (up to 75%) resulted upon addition of the coenzyme analogue to PDHc-h. With PDHc-ec and PDHc-h, the coenzyme analogue could support all reactions, including communication between components in the complex. No functional substitution of MeOThDP for ThDP was in evidence with either OGDH-h or OGDH-ec, shown to be due to tight binding of ThDP. PMID- 26813611 TI - Sexual Orientation, Objective Height, and Self-Reported Height. AB - Studies that have used mostly self-reported height have found that androphilic men and women are shorter than gynephilic men and women, respectively. This study examined whether an objective height difference exists or whether a psychosocial account (e.g., distortion of self-reports) may explain these putative height differences. A total of 863 participants, recruited at a Canadian university, the surrounding region, and through lesbian, gay, bisexual, and transgender (LGBT) events across Canada, self-reported their height and had their height measured. Androphilic men were shorter, on average, than gynephilic men. There was no objective height difference between gynephilic, ambiphilic, and androphilic women. Self-reported height, statistically controlling for objective height, was not related to sexual orientation. These findings are the first to show an objective height difference between androphilic and gynephilic men. Also, the findings suggest that previous studies using self-reported height found part of a true objective height difference between androphilic and gynephilic men. These findings have implications for existing biological theories of men's sexual orientation development. PMID- 26813612 TI - Application of Controlled Shear Stresses on the Erythrocyte Membrane as a New Approach to Promote Molecule Encapsulation. AB - Human red blood cells (RBCs) have a remarkable capacity to undergo reversible membrane swelling. Resealed erythrocytes have been proposed as carriers and bioreactors to be used in the treatment of various diseases. This work is aimed at developing a setup allowing the encapsulation of test molecules into erythrocytes by inducing reversible pore formation on the RBC membrane through the application of controlled mechanical shear stresses. The designed setup consists of two reservoirs connected by a glass capillary. Each reservoir is connected to a compressor; during the tests, the reservoirs were in turn pressurized to promote erythrocyte flow through the capillary. The setup was filled with a suspension of erythrocytes, phosphate buffer, and FITC-dextran. Dextran was chosen as the diffusive molecule to check membrane pore dimensions. Samples of the suspension were withdrawn at scheduled times while the setup was operating. Flow cytometry and stereo-optical microscopy analyses were used to evaluate the erythrocyte dextran uptake. The setup was shown to be safe, well controlled, and adjustable. The outcomes of the experimental tests showed significant dextran uptake by RBCs up to 8%. Microscopy observations highlighted the formation of echinocytes in the analyzed samples. Erythrocytes from different donors showed different reactions to mechanical stresses. The experimental outcomes proved the possibility to encapsulate test molecules into erythrocytes by applying controlled mechanical shear stresses on the RBC membrane, encouraging further studies. PMID- 26813613 TI - Editorial. PMID- 26813614 TI - IWGDF guidance on footwear and offloading interventions to prevent and heal foot ulcers in patients with diabetes. PMID- 26813615 TI - Sedentary behaviour as a new behavioural target in the prevention and treatment of type 2 diabetes. AB - Our modern day society encompasses an ecological niche in which sedentary behaviour, labour-saving devices and energy dense foods have become the new reference of living. We now spend more time sedentary, defined as sitting, than in all other activities combined. It has recently been confirmed that the consequences of our modern chair dependency are substantial and a direct contributing factor to the ever increasing epidemic of chronic diseases witnessed within industrialized environments. Epidemiological evidence--from both cross sectional and prospective observational studies--has indicated that the time spent in sedentary behaviour is a distinct risk factor for several health outcomes, including type 2 diabetes mellitus, insulin resistance, all-cause and cardiovascular disease mortality, depression and some types of cancer. Importantly, these detrimental associations remain even after accounting for time spent in moderate-to-vigorous physical activity, with the strongest and most persistent associations seen between sedentary time and type 2 diabetes mellitus. Importantly, experimental studies have started to confirm the observational associations, with mounting evidence showing that breaking prolonged sitting time with light ambulation is an effective strategy for improving postprandial glucose regulation. Indeed, there is even emerging evidence showing that simply substituting sitting for standing regularly throughout the day may be of sufficient stimulus to improve glucose regulation. We highlight some of the key definitions, issues and evidence underpinning the link between sedentary behaviour and chronic disease in order to better inform clinicians and patients about the importance of incorporating reduced sitting time into type 2 diabetes mellitus management and prevention pathways. PMID- 26813616 TI - Assessment of foot perfusion in patients with a diabetic foot ulcer. AB - Assessment of foot perfusion is a vital step in the management of patients with diabetic foot ulceration, in order to understand the risk of amputation and likelihood of wound healing. Underlying peripheral artery disease is a common finding in patients with foot ulceration and is associated with poor outcomes. Assessment of foot perfusion should therefore focus on identifying the presence of peripheral artery disease and to subsequently estimate the effect this may have on wound healing. Assessment of perfusion can be difficult because of the often complex, diffuse and distal nature of peripheral artery disease in patients with diabetes, as well as poor collateralisation and heavy vascular calcification. Conventional methods of assessing tissue perfusion in the peripheral circulation may be unreliable in patients with diabetes, and it may therefore be difficult to determine the extent to which poor perfusion contributes to foot ulceration. Anatomical data obtained on cross-sectional imaging is important but must be combined with measurements of tissue perfusion (such as transcutaneous oxygen tension) in order to understand the global and regional perfusion deficit present in a patient with diabetic foot ulceration. Ankle-brachial pressure index is routinely used to screen for peripheral artery disease, but its use in patients with diabetes is limited in the presence of neuropathy and medial arterial calcification. Toe pressure index may be more useful because of the relative sparing of pedal arteries from medial calcification but may not always be possible in patients with ulceration. Fluorescence angiography is a non-invasive technique that can provide rapid quantitative information about regional tissue perfusion; capillaroscopy, iontophoresis and hyperspectral imaging may also be useful in assessing physiological perfusion but are not widely available. There may be a future role for specialized perfusion imaging of these patients, including magnetic resonance imaging techniques, single-photon emission computed tomography and PET-based molecular imaging; however, these novel techniques require further validation and are unlikely to become standard practice in the near future. PMID- 26813617 TI - Pitfalls in diagnosing diabetic foot infections. AB - Although the diagnosis of a diabetic foot infection is made based on clinical symptoms and signs, we also use blood laboratory, microbiological and radiological studies to make treatment decisions. All of these diagnostic studies have pitfalls that can lead to a delay in diagnosis. Such delays will likely lead to further tissue damage and to a higher chance of amputation. One of these pitfalls is that some clinicians rely on microbiological, rather than clinical data, to diagnose infection. Though subjective by nature, clinical signs predict outcome of foot infections accurately. Another pitfall is that microbiological data can be misleading. All wounds harbour microorganisms; therefore, a positive wound culture does not mean that a wound is infected. Furthermore, the outcome of cultures of wound swabs does not correlate well with culture results of tissue biopsies. Therapy guidance by wound swab will likely lead to overtreatment of non pathogenic organisms. Genotyping might have a role in identifying previously unrecognized (combinations of) pathogens in diabetic foot infection, bacteria in sessile phenotype and non-culturable pathogens, e.g. in cases where antibiotics have already been administered. One more pitfall is that the diagnosis of osteomyelitis remains difficult. Although the result of percutaneous bone biopsy is the reference standard for osteomyelitis, some other diagnostic modalities can aid in the diagnosis. A combination of several of these diagnostic tests is probably a good strategy to achieve a higher diagnostic accuracy. Relying on a single test will likely lead to misidentification of patients with osteomyelitis with associated overtreatment and undertreatment. PMID- 26813618 TI - Innovations in diabetic foot reconstruction using supermicrosurgery. AB - The treatment of diabetic foot ulceration is complex with multiple factors involved, and it may often lead to limb amputation. Hence, a multidisciplinary approach is warranted to cover the spectrum of treatment for diabetic foot, but in complex wounds, surgical treatment is inevitable. Surgery may involve the decision to preserve the limb by reconstruction or to amputate it. Reconstruction involves preserving the limb with secure coverage. Local flaps usually are able to provide sufficient coverage for small or moderate sized wound, but for larger wounds, soft tissue coverage involves flaps that are distantly located from the wound. Reconstruction of distant flap usually involves microsurgery, and now, further innovative methods such as supermicrosurgery have further given complex wounds a better chance to be reconstructed and limbs salvaged. This article reviews the microsurgery involved in reconstruction and introduces the new method of supermicrosurgery. PMID- 26813619 TI - Surgical treatment of the Charcot foot. AB - With the increased number of diabetics worldwide and the increased incidence of morbid obesity in more prosperous cultures, there has become an increased awareness of Charcot arthropathy of the foot and ankle. Outcome studies would suggest that patients with deformity associated with Charcot Foot arthropathy have impaired health related quality of life. This awareness has led reconstructive-minded foot and ankle surgeons to develop surgical strategies to treat these acquired deformities. This article outlines the current clinical approach to this disabling medical condition. PMID- 26813620 TI - Integrating palliative care with usual care of diabetic foot wounds. AB - Palliative care is a philosophy and a system for deciding care and can be used alone or integrated with usual chronic disease care. Palliative care encompasses end-of-life care. Palliative care aims to enhance quality of life, optimize function and manage symptoms including early in the course of chronic diseases. The purposes of this article are to outline palliative care and discuss how it can be integrated with usual care of diabetic foot wounds. Many people with diabetes who have foot wounds also have other comorbidities and diabetes complications such as cardiovascular and renal disease and depression, which affect medicine and other treatment choices, functional status, surgical risk and quality of life. Two broad of diabetic foot disease exist: those likely to heal but who could still benefit from integrated palliative care such as managing pain and those where healing is unlikely where palliation can be the primary focus. People with diabetes can die suddenly, although the life course is usually long with periods of stable and unstable disease. Many health professionals are reluctant to discuss palliative care or suggest people to document their end-of life care preferences. If such preferences are not documented, the person might not achieve their desired death or place of death and health professionals and families can be confronted with difficult decisions. Palliative care can be integrated with usual foot care and is associated with improved function, better quality of life and greater patient and family satisfaction. PMID- 26813621 TI - Interactions of C4 Subtype Metabolic Activities and Transport in Maize Are Revealed through the Characterization of DCT2 Mutants. AB - C4 photosynthesis in grasses requires the coordinated movement of metabolites through two specialized leaf cell types, mesophyll (M) and bundle sheath (BS), to concentrate CO2 around Rubisco. Despite the importance of transporters in this process, few have been identified or rigorously characterized. In maize (Zea mays), DCT2 has been proposed to function as a plastid-localized malate transporter and is preferentially expressed in BS cells. Here, we characterized the role of DCT2 in maize leaves using Activator-tagged mutant alleles. Our results indicate that DCT2 enables the transport of malate into the BS chloroplast. Isotopic labeling experiments show that the loss of DCT2 results in markedly different metabolic network operation and dramatically reduced biomass production. In the absence of a functioning malate shuttle, dct2 lines survive through the enhanced use of the phosphoenolpyruvate carboxykinase carbon shuttle pathway that in wild-type maize accounts for ~ 25% of the photosynthetic activity. The results emphasize the importance of malate transport during C4 photosynthesis, define the role of a primary malate transporter in BS cells, and support a model for carbon exchange between BS and M cells in maize. PMID- 26813622 TI - Pectin Biosynthesis Is Critical for Cell Wall Integrity and Immunity in Arabidopsis thaliana. AB - Plant cell walls are important barriers against microbial pathogens. Cell walls of Arabidopsis thaliana leaves contain three major types of polysaccharides: cellulose, various hemicelluloses, and pectins. UDP-D-galacturonic acid, the key building block of pectins, is produced from the precursor UDP-D-glucuronic acid by the action of glucuronate 4-epimerases (GAEs). Pseudomonas syringae pv maculicola ES4326 (Pma ES4326) repressed expression of GAE1 and GAE6 in Arabidopsis, and immunity to Pma ES4326 was compromised in gae6 and gae1 gae6 mutant plants. These plants had brittle leaves and cell walls of leaves had less galacturonic acid. Resistance to specific Botrytis cinerea isolates was also compromised in gae1 gae6 double mutant plants. Although oligogalacturonide (OG) induced immune signaling was unaltered in gae1 gae6 mutant plants, immune signaling induced by a commercial pectinase, macerozyme, was reduced. Macerozyme treatment or infection with B. cinerea released less soluble uronic acid, likely reflecting fewer OGs, from gae1 gae6 cell walls than from wild-type Col-0. Although both OGs and macerozyme-induced immunity to B. cinerea in Col-0, only OGs also induced immunity in gae1 gae6. Pectin is thus an important contributor to plant immunity, and this is due at least in part to the induction of immune responses by soluble pectin, likely OGs, that are released during plant-pathogen interactions. PMID- 26813623 TI - The Opposing Actions of Arabidopsis CHROMOSOME TRANSMISSION FIDELITY7 and WINGS APART-LIKE1 and 2 Differ in Mitotic and Meiotic Cells. AB - Sister chromatid cohesion, which is mediated by the cohesin complex, is essential for the proper segregation of chromosomes during mitosis and meiosis. Stable binding of cohesin with chromosomes is regulated in part by the opposing actions of CTF7 (CHROMOSOME TRANSMISSION FIDELITY7) and WAPL (WINGS APART-LIKE). In this study, we characterized the interaction between Arabidopsis thaliana CTF7 and WAPL by conducting a detailed analysis of wapl1-1 wapl2 ctf7 plants. ctf7 plants exhibit major defects in vegetative growth and development and are completely sterile. Inactivation of WAPL restores normal growth, mitosis, and some fertility to ctf7 plants. This shows that the CTF7/WAPL cohesin system is not essential for mitosis in vegetative cells and suggests that plants may contain a second mechanism to regulate mitotic cohesin. WAPL inactivation restores cohesin binding and suppresses ctf7-associated meiotic cohesion defects, demonstrating that WAPL and CTF7 function as antagonists to regulate meiotic sister chromatid cohesion. The ctf7 mutation only had a minor effect on wapl-associated defects in chromosome condensation and centromere association. These results demonstrate that WAPL has additional roles that are independent of its role in regulating chromatin-bound cohesin. PMID- 26813624 TI - General Health status of workers among different workplaces in Qom Province, Iran. AB - INTRODUCTION: In a healthy organization, psychological health and physical health are as important as production and productivity; and healthy workers have higher productivity. Regarding lack of information about workers' general health profile in Qom Province, this study aimed to assess and compare the staffs' general health and its components among different workplaces in 2014. METHODS: In a cross sectional study, 2,276 employees working at 46 industries and organizations completed a standardized General Health Questionnaire (GHQ 28) and a demographic questionnaire. Data were analyzed using t-test, ANOVA, and Pearson product-moment correlation coefficient by IBM SPSS version 20. RESULTS: The mean age of the participants was 32.22 (+/-7.55) years. Seventy-nine point four percent of participants were married and the rest were single. Highest and lowest scores belonged to social dysfunction and depression, respectively. Also, total score of staffs' general health was 17.87 +/- 10.93. The results showed that, in spite of the non-relationship between general health score difference among married and single personnel (p > 0.05), there was a significant difference between men and women and among organizations and industries with regards to general health score (p < 0.05), and drivers had the most difference with others. The relationship between workers' ages and GH was significant (p < 0.05, Pearson's bivariate correlation coefficient = -0.05). CONCLUSION: The findings of this study collectively indicated that participants had an acceptable condition for mental factors, such as depression, but not in viewpoints of social dysfunction. In other words, staffs' interfaces with circumstances and personal innovation/creativity in the workplaces are at risk. Altogether, the general health score in the studied population was suitable in its entirety. PMID- 26813626 TI - The Therapeutic Approach to a Patient's Criminal Offense in a Forensic Mental Health Nurse-Patient Relationship-The Nurses' Perspectives. AB - PURPOSE: The purpose of this study is to describe the therapeutic approach to a patient's criminal offense in a forensic mental health nurse-patient relationship from the nurse's perspective. DESIGN AND METHODS: Eight nurses in a Finnish forensic psychiatric hospital were interviewed, and the resultant research material was analyzed by inductive content analysis. FINDINGS: The results revealed the process of the therapeutic approach to a patient's offense, which comprises numerous steps and various phases. PRACTICE IMPLICATIONS: For the nurse, the process of working through the offense can be divided into stages in which an attempt is made to respond to the patient's behavior and interaction in a manner that leads to working through the criminal act. PMID- 26813627 TI - Fouling on ion-exchange membranes: Classification, characterization and strategies of prevention and control. AB - The environmentally friendly ion-exchange membrane (IEM) processes find more and more applications in the modern industries in order to demineralize, concentrate and modify products. Moreover, these processes may be applied for the energy conversion and storage. However, the main drawback of the IEM processes is a formation of fouling, which significantly decreases the process efficiency and increases the process cost. The present review is dedicated to the problematic of IEM fouling phenomena. Firstly, the major types of IEM fouling such as colloidal fouling, organic fouling, scaling and biofouling are discussed along with consideration of the main factors affecting fouling formation and development. Secondly, the review of the possible methods of IEM fouling characterization is provided. This section includes the methods of fouling visualization and characterization as well as methods allowing investigations of characteristics of the fouled IEMs. Eventually, the reader will find the conventional and modern strategies of prevention and control of different fouling types. PMID- 26813625 TI - The role of microRNAs in prostate cancer progression. AB - Prostate cancer (PCa) is the most common male malignancy and the second highest cause of cancer-related mortality in United States. MicroRNAs (miRNAs) are small non-coding RNAs that represent a new mechanism to regulate mRNA post transcriptionally. It is involved in diverse physiological and pathophysiological process. Dysregulation of miRNAs has been associated with the multistep progression of PCa from prostatic intraepithelial neoplasia (PIN), localized adenocarcinoma to metastatic castration-resistance PCa (CRPC). Identification of unique miRNA could provide new biomarkers for PCa and develop into therapeutic strategies. In this review, we will summarize a broad spectrum of both tumor suppressive and oncogenic miRNAs, and their mechanisms contribute to prostate carcinogenesis. PMID- 26813628 TI - Bundling in semiflexible polymers: A theoretical overview. AB - Supramolecular assemblies of polymers are key modules to sustain the structure of cells and their function. The main elements of these assemblies are charged semiflexible polymers (polyelectrolytes) generally interacting via a long(er) range repulsion and a short(er)-range attraction. The most common supramolecular structure formed by these polymers is the bundle. In the present paper, we critically review some recent theoretical and computational advances on the problem of bundle formation, and point a few promising directions for future work. PMID- 26813629 TI - Effect of Strength and Power Training on Tackling Ability in Semiprofessional Rugby League Players. AB - This study examined the influence of a strength and power program on tackling ability in rugby league players. Twenty-four semiprofessional rugby league players (mean +/- SD age, 23.4 +/- 3.1 years) underwent tests of upper-body strength (3 repetition maximum [RM] bench press), lower-body strength (3RM squat), upper-body power (plyometric push-up), and lower-body power (countermovement jump [CMJ]). Muscular strength relative to body mass was also calculated. Tackling ability of the players was assessed using video analysis of a standardized one-on-one tackling drill. The players then underwent 8 weeks of strength and power training as part of their preseason training before being retested. Training resulted in significant (p <= 0.01) improvements in absolute and relative measures of squat, bench press, CMJ peak power, and plyometric push up peak power. The strongest correlates of change in tackling ability were changes in 3RM squat (r = 0.60; p < 0.01) and squat relative to body mass (r = 0.54; p < 0.01). The players with the greatest improvements in 3RM squat and squat relative to body mass (i.e., responders) had significantly greater improvements in tackling ability than nonresponding players (p = 0.04; effect size [ES] >= 0.85). A small, nonsignificant difference (p = 0.20; ES = 0.56) in tackling ability was found between responders and nonresponders for lower-body power. The findings of this study demonstrate that the enhancement of lower-body muscular strength, and to a lesser extent muscular power, contribute to improvements in tackling ability in semiprofessional rugby league players. PMID- 26813630 TI - Comparative Effects of In-Season Full-Back Squat, Resisted Sprint Training, and Plyometric Training on Explosive Performance in U-19 Elite Soccer Players. AB - The aim of this study was to analyze the effects of 3 different low/moderate load strength training methods (full-back squat [SQ], resisted sprint with sled towing [RS], and plyometric and specific drills training [PLYO]) on sprinting, jumping, and change of direction (COD) abilities in soccer players. Thirty-two young elite male Spanish soccer players participated in the study. Subjects performed 2 specific strength training sessions per week, in addition to their normal training sessions for 8 weeks. The full-back squat protocol consisted of 2-3 sets * 4-8 repetitions at 40-60% 1 repetition maximum (~ 1.28-0.98 m . s(-1)). The resisted sprint training was compounded by 6-10 sets * 20-m loaded sprints (12.6% of body mass). The plyometric and specific drills training was based on 1-3 sets * 2-3 repetitions of 8 plyometric and speed/agility exercises. Testing sessions included a countermovement jump (CMJ), a 20-m sprint (10-m split time), a 50-m (30-m split time) sprint, and COD test (i.e., Zig-Zag test). Substantial improvements (likely to almost certainly) in CMJ (effect size [ES]: 0.50-0.57) and 30-50 m (ES: 0.45-0.84) were found in every group in comparison to pretest results. Moreover, players in PLYO and SQ groups also showed substantial enhancements (likely to very likely) in 0-50 m (ES: 0.46-0.60). In addition, 10 20 m was also improved (very likely) in the SQ group (ES: 0.61). Between-group analyses showed that improvements in 10-20 m (ES: 0.57) and 30-50 m (ES: 0.40) were likely greater in the SQ group than in the RS group. Also, 10-20 m (ES: 0.49) was substantially better in the SQ group than in the PLYO group. In conclusion, the present strength training methods used in this study seem to be effective to improve jumping and sprinting abilities, but COD might need other stimulus to achieve positive effects. PMID- 26813631 TI - Acute Effects of Two Different Resistance Circuit Training Protocols on Performance and Perceived Exertion in Semiprofessional Basketball Players. AB - This study aimed to investigate the acute effects of two different resistance circuit training protocols on basketball players' physical and technical performance and rating of perceived exertion (RPE). In a repeated-measures, crossover experimental design, 9 semiprofessional basketball players performed a Power Circuit Training (PCT; 45% 1RM) and a High-Resistance Circuit Training (HRC; 6RM), on consecutive weeks. Vertical and horizontal jump performance, 3 points shooting accuracy, repeated-sprint ability (RSA), agility, and upper body power output were measured before and after training. The RPE was assessed 20 minutes after resistance training. One-way repeated-measures analysis of variance showed performance decrements in vertical jump height and peak power, horizontal jump distance, 3-points percentage, bench-press power output, RSA total and ideal time, and agility T-Test at total time following HRC, but not PCT (p <= 0.05). The RPE was higher in HRC compared with PCT. The results of this study indicated that HRC was perceived as being harder and produced higher fatigue levels, which in turn lowered acute performance. However, low-to-moderate intensity loads did not negatively affect performance. Thus, completing a PCT session may be the most appropriate option before a practice or game as it avoids acute-resistance training-induced performance decrements. However, if the objective of the basketball session is to develop or perfect technical skills during fatiguing conditions, HRC may be the more suitable option. PMID- 26813632 TI - Influence of Postactivation Potentiation on Shot Put Performance of Collegiate Throwers. AB - The purpose of this investigation was to determine the acute effects of heavy and light implements on subsequent overhead back (OHB) shot put performance with a competition weight shot put. This investigation was designed to test the efficacy of heavy implements for potentiating subsequent OHB performance. Participants included 41 athletes (20.9 +/- 1.18 years.) from 2 National Collegiate Athletic Association Division I schools in the Midwestern United States (n = 23 male and n = 18 female). Mean distance for OHB throw with a competition shot put was examined after treatment (control, light shot put warm-up, and heavy shot put warm-up) through repeated-measures analysis of variance (ANOVA) with post hoc Bonferroni-corrected post hoc analysis. Responses after treatment on the 10-cm visual analog scale (VAS) fatigue were examined through repeated-measures ANOVA and demonstrated a significant main effect for treatment on VAS fatigue (F = 16.463; p = 0.001). The heavy shot put warm-up resulted in the greatest mean performance over the course of the 3 attempts (14.39 +/- 1.82 m) followed by the light shot put warm-up (14.18 +/- 1.68 m) and the control (14.15 +/- 1.70 m). Results of the repeated-measures ANOVA demonstrated a significant main effect for treatment in regard to average distance (F = 6.276; p = 0.003). Post hoc testing suggested that the heavy shot put warm-up resulted in significantly better mean OHB performance than either the light shot put warm-up (t = 2.983; p = 0.0048; ES = 0.472; power = 0.901) or the control shot put warm-up (t = 3.349; p = 0.0018; effect size [ES] = 0.513; power = 0.939). Subsequent analysis examined the relationship between reported fatigue accrued during the overweight shot put warm up and the change in performance on the OHB throw when compared to the control condition. Analysis revealed that subjects who reported higher levels of VAS fatigue did not perform as well after the overweight treatment (p = 0.0274). PMID- 26813633 TI - Aerobic Conditioning Might Protect Against Liver and Muscle Injury Caused by Short-Term Military Training. AB - This study aimed to compare the biochemical markers of muscle and liver injury and total antioxidant capacity in army cadets after a traditional army physical training program and to correlate these effects with aerobic conditioning. Male army cadets (n = 87; age, 20 +/- 2 years) were evaluated 12 hours before the start of training (T0), 12 hours after a 30-km march (T1), and 48 hours after military training (T2). Creatine kinase (CK), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) serum levels were measured using an autoanalyzer. Total antioxidant capacity was determined by 2,2-diphenyl-1 picrylhydrazyl radical scavenging activity (Sc%). Seventy-four percent of army cadets were classified as having excellent aerobic conditioning (53.9 +/- 3.0 ml . kg(-) . min(-1) predicted VO2max from the Cooper test). The median serum concentration of all enzymes increased 12 hours after marching (T1: CK 675%; ALT 59%; AST 336%; AST/ALT ratio 85%; p = 0.001) and 48 hours after the end of training (T2: CK 878%; ALT 256%; AST 418%; AST/ALT ratio 180%; p = 0.001). Sc% was higher in T2 (31.1 +/- 9.8%; p = 0.01) than in T0 (3.4% change). Maximal oxygen consumption (ml . kg(-1) . min(-1)) correlated negatively with CK (r = 0.25; p = 0.009) and ALT (r = -0.21; p = 0.03) serum levels, and positively with the change in Sc% (r = 0.22; p = 0.04) at T2. The results indicate that intense military training can cause liver and muscle injury and that aerobic conditioning can be considered as a protective factor for these injuries. PMID- 26813634 TI - Effect of Peer Influence on Exercise Behavior and Enjoyment in Recreational Runners. AB - Fitness professionals and popular media sources often recommend exercising with a partner to increase exercise motivation, adherence, intensity, and/or duration. Although competition with peers has been shown to enhance maximal athletic performance, experimental research examining the impact of peer influence on submaximal exercise behavior in adults is limited. The purpose of this study was to determine the effects of the presence of familiar and unfamiliar peers, vs. running alone, on recreational runners' voluntary running duration, distance, intensity, liking (i.e., enjoyment), and ratings of perceived exertion (RPEs). Recreational runners (n = 12 males, n = 12 females) completed 3 experimental trials, each under a different social condition, in a randomized order. Each trial consisted of self-paced running for a duration voluntarily determined by the participant. The 3 social conditions were running alone, with a sex- and fitness-matched familiar peer, or with a sex- and fitness-matched unfamiliar peer. A wrist-worn global positioning system was used to record running duration, distance, and average speed. Liking and RPE were assessed at the end of each trial. Mixed model regression analysis showed no significant effects of social condition (p >= 0.40) for any of the dependent variables. The presence of a familiar or unfamiliar peer did not alter recreational runners' running behavior, liking, or perceived exertion during submaximal exercise. However, exercising with others may have other benefits (e.g., reduced attrition) not examined herein. PMID- 26813635 TI - PMD: A Resource for Archiving and Analyzing Protein Microarray data. AB - Protein microarray is a powerful technology for both basic research and clinical study. However, because there is no database specifically tailored for protein microarray, the majority of the valuable original protein microarray data is still not publically accessible. To address this issue, we constructed Protein Microarray Database (PMD), which is specifically designed for archiving and analyzing protein microarray data. In PMD, users can easily browse and search the entire database by experimental name, protein microarray type, and sample information. Additionally, PMD integrates several data analysis tools and provides an automated data analysis pipeline for users. With just one click, users can obtain a comprehensive analysis report for their protein microarray data. The report includes preliminary data analysis, such as data normalization, candidate identification, and an in-depth bioinformatics analysis of the candidates, which include functional annotation, pathway analysis, and protein protein interaction network analysis. PMD is now freely available at www.proteinmicroarray.cn. PMID- 26813636 TI - Melanocyte reprogramming requires chromatin and transcription remodelling. PMID- 26813637 TI - Distinct cognitive effects and underlying transcriptome changes upon inhibition of individual miRNAs in hippocampal neurons. AB - MicroRNAs (miRNA) are small, non-coding RNAs mediating post-transcriptional regulation of gene expression. miRNAs have recently been implicated in hippocampus-dependent functions such as learning and memory, although the roles of individual miRNAs in these processes remain largely unknown. Here, we achieved stable inhibition using AAV-delivered miRNA sponges of individual, highly expressed and brain-enriched miRNAs; miR-124, miR-9 and miR-34, in hippocampal neurons. Molecular and cognitive studies revealed a role for miR-124 in learning and memory. Inhibition of miR-124 resulted in an enhanced spatial learning and working memory capacity, potentially through altered levels of genes linked to synaptic plasticity and neuronal transmission. In contrast, inhibition of miR-9 or miR-34 led to a decreased capacity of spatial learning and of reference memory, respectively. On a molecular level, miR-9 inhibition resulted in altered expression of genes related to cell adhesion, endocytosis and cell death, while miR-34 inhibition caused transcriptome changes linked to neuroactive ligand receptor transduction and cell communication. In summary, this study establishes distinct roles for individual miRNAs in hippocampal function. PMID- 26813639 TI - Trust Is a Two-Way Street. PMID- 26813638 TI - Electrochemical camera chip for simultaneous imaging of multiple metabolites in biofilms. AB - Monitoring spatial distribution of metabolites in multicellular structures can enhance understanding of the biochemical processes and regulation involved in cellular community development. Here we report on an electrochemical camera chip capable of simultaneous spatial imaging of multiple redox-active phenazine metabolites produced by Pseudomonas aeruginosa PA14 colony biofilms. The chip features an 8 mm * 8 mm array of 1,824 electrodes multiplexed to 38 parallel output channels. Using this chip, we demonstrate potential-sweep-based electrochemical imaging of whole-biofilms at measurement rates in excess of 0.2 s per electrode. Analysis of mutants with various capacities for phenazine production reveals distribution of phenazine-1-carboxylic acid (PCA) throughout the colony, with 5-methylphenazine-1-carboxylic acid (5-MCA) and pyocyanin (PYO) localized to the colony edge. Anaerobic growth on nitrate confirms the O2 dependence of PYO production and indicates an effect of O2 availability on 5-MCA synthesis. This integrated-circuit-based technique promises wide applicability in detecting redox-active species from diverse biological samples. PMID- 26813640 TI - More on Promoting Medical Student Scholarly Research. PMID- 26813641 TI - More on Promoting Medical Student Scholarly Research. PMID- 26813642 TI - In Reply to Rosenkranz and Hu and to Wolfson and Arora. PMID- 26813643 TI - A Critical Look at the "Problem" With Competencies in Global Health Education. PMID- 26813644 TI - In Reply to Hagopian. PMID- 26813645 TI - "Taxes," "Antes," and "Bonuses": More on the Realities of Global Health Careers. PMID- 26813646 TI - "Taxes," "Antes," and "Bonuses": More on the Realities of Global Health Careers. PMID- 26813647 TI - In Reply to Lukolyo and Haq and to Loh. PMID- 26813648 TI - Addressing Implicit Bias: Leading by Example. PMID- 26813649 TI - In Reply to Williams. PMID- 26813650 TI - Obesity Education Beyond Nutrition Education: Thinking Farther Outside the Box. PMID- 26813652 TI - Letter to a Funeral Parlor. PMID- 26813653 TI - Commentary on "Letter to a Funeral Parlor". PMID- 26813654 TI - An E-mail to My Residents. PMID- 26813655 TI - Applying Kolb's Learning Cycle to Competency-Based Residency Education. PMID- 26813656 TI - Sinorhizobium meliloti low molecular mass phosphotyrosine phosphatase SMc02309 modifies activity of the UDP-glucose pyrophosphorylase ExoN involved in succinoglycan biosynthesis. AB - In Gram-negative bacteria, tyrosine phosphorylation has been shown to play a role in the control of exopolysaccharide (EPS) production. This study demonstrated that the chromosomal ORF SMc02309 from Sinorhizobium meliloti 2011 encodes a protein with significant sequence similarity to low molecular mass protein tyrosine phosphatases (LMW-PTPs), such as the Escherichia coli Wzb. Unlike other well-characterized EPS biosynthesis gene clusters, which contain neighbouring LMW PTPs and kinase, the S. meliloti succinoglycan (EPS I) gene cluster located on megaplasmid pSymB does not encode a phosphatase. Biochemical assays revealed that the SMc02309 protein hydrolyses p-nitrophenyl phosphate (p-NPP) with kinetic parameters similar to other bacterial LMW-PTPs. Furthermore, we show evidence that SMc02309 is not the LMW-PTP of the bacterial tyrosine-kinase (BY-kinase) ExoP. Nevertheless, ExoN, a UDP-glucose pyrophosphorylase involved in the first stages of EPS I biosynthesis, is phosphorylated at tyrosine residues and constitutes an endogenous substrate of the SMc02309 protein. Additionally, we show that the UDP-glucose pyrophosphorylase activity is modulated by SMc02309 mediated tyrosine dephosphorylation. Moreover, a mutation in the SMc02309 gene decreases EPS I production and delays nodulation on Medicago sativa roots. PMID- 26813657 TI - Vector-borne transmission of Trypanosoma cruzi among captive Neotropical primates in a Brazilian zoo. AB - BACKGROUND: Neotropical primates are important sylvatic hosts of Trypanosoma cruzi, the etiological agent of Chagas disease. Infection is often subclinical, but severe disease has been described in both free-ranging and captive primates. Panstrongylus megistus, a major T. cruzi vector, was found infesting a small primate unit at Brasilia zoo (ZooB), Brazil. ZooB lies close to a gallery-forest patch where T. cruzi circulates naturally. Here, we combine parasitological and molecular methods to investigate a focus of T. cruzi infection involving triatomine bugs and Neotropical primates at a zoo located in the Brazilian Savannah. METHODS: We assessed T. cruzi infection in vectors using optical microscopy (n = 34) and nested PCR (n = 50). We used quantitative PCR (qPCR) to examine blood samples from 26 primates and necropsy samples from two primates that died during the study. We determined parasite lineages in five vectors and two primates by comparing glucose-6-phosphate isomerase (G6pi) gene sequences. RESULTS: Trypanosoma cruzi was found in 44 vectors and 17 primates (six genera and eight species); one Mico chrysoleucus and one Saguinus niger had high parasitaemias. Trypanosoma cruzi DNA was detected in three primates born to qPCR negative mothers at ZooB and in the two dead specimens. One Callithrix geoffroyi became qPCR-positive over a two-year follow-up. All G6pi sequences matched T. cruzi lineage TcI. CONCLUSIONS: Our findings strongly suggest vector-borne T. cruzi transmission within a small-primate unit at ZooB - with vectors, and perhaps also parasites, presumably coming from nearby gallery forest. Periodic checks for vectors and parasites would help eliminate T. cruzi transmission foci in captive-animal facilities. This should be of special importance for captive breeding programs involving endangered mammals, and would reduce the risk of accidental T. cruzi transmission to keepers and veterinarians. PMID- 26813658 TI - Kinetic Approaches to Measuring Peroxiredoxin Reactivity. AB - Peroxiredoxins are ubiquitous thiol proteins that catalyse the breakdown of peroxides and regulate redox activity in the cell. Kinetic analysis of their reactions is required in order to identify substrate preferences, to understand how molecular structure affects activity and to establish their physiological functions. Various approaches can be taken, including the measurement of rates of individual steps in the reaction pathway by stopped flow or competitive kinetics, classical enzymatic analysis and measurement of peroxidase activity. Each methodology has its strengths and they can often give complementary information. However, it is important to understand the experimental conditions of the assay so as to interpret correctly what parameter is being measured. This brief review discusses different kinetic approaches and the information that can be obtained from them. PMID- 26813659 TI - Microbial 2-Cys Peroxiredoxins: Insights into Their Complex Physiological Roles. AB - The peroxiredoxins (Prxs) constitute a very large and highly conserved family of thiol-based peroxidases that has been discovered only very recently. We consider here these enzymes through the angle of their discovery, and of some features of their molecular and physiological functions, focusing on complex phenotypes of the gene mutations of the 2-Cys Prxs subtype in yeast. As scavengers of the low levels of H2O2 and as H2O2 receptors and transducers, 2-Cys Prxs have been highly instrumental to understand the biological impact of H2O2, and in particular its signaling function. 2-Cys Prxs can also become potent chaperone holdases, and unveiling the in vivo relevance of this function, which is still not established, should further increase our knowledge of the biological impact and toxicity of H2O2. The diverse molecular functions of 2-Cys Prx explain the often-hard task of relating them to peroxiredoxin genes phenotypes, which underscores the pleiotropic physiological role of these enzymes and complex biologic impact of H2O2. PMID- 26813660 TI - Peroxiredoxins in Regulation of MAPK Signalling Pathways; Sensors and Barriers to Signal Transduction. AB - Peroxiredoxins are highly conserved and abundant peroxidases. Although the thioredoxin peroxidase activity of peroxiredoxin (Prx) is important to maintain low levels of endogenous hydrogen peroxide, Prx have also been shown to promote hydrogen peroxide-mediated signalling. Mitogen activated protein kinase (MAPK) signalling pathways mediate cellular responses to a variety of stimuli, including reactive oxygen species (ROS). Here we review the evidence that Prx can act as both sensors and barriers to the activation of MAPK and discuss the underlying mechanisms involved, focusing in particular on the relationship with thioredoxin. PMID- 26813661 TI - Multiple Roles of Peroxiredoxins in Inflammation. AB - Inflammation is a pathophysiological response to infection or tissue damage during which high levels of reactive oxygen and nitrogen species are produced by phagocytes to kill microorganisms. Reactive oxygen and nitrogen species serve also in the complex regulation of inflammatory processes. Recently, it has been proposed that peroxiredoxins may play key roles in innate immunity and inflammation. Indeed, peroxiredoxins are evolutionarily conserved peroxidases able to reduce, with high rate constants, hydrogen peroxide, alkyl hydroperoxides and peroxynitrite which are generated during inflammation. In this minireview, we point out different possible roles of peroxiredoxins during inflammatory processes such as cytoprotective enzymes against oxidative stress, modulators of redox signaling, and extracellular pathogen- or damage-associated molecular patterns. A better understanding of peroxiredoxin functions in inflammation could lead to the discovery of new therapeutic targets. PMID- 26813663 TI - 'Classic Papers' in this issue of Acta Radiologica. PMID- 26813662 TI - The Roles of Peroxiredoxin and Thioredoxin in Hydrogen Peroxide Sensing and in Signal Transduction. AB - A challenge in the redox field is the elucidation of the molecular mechanisms, by which H2O2 mediates signal transduction in cells. This is relevant since redox pathways are disturbed in some pathologies. The transcription factor OxyR is the H2O2 sensor in bacteria, whereas Cys-based peroxidases are involved in the perception of this oxidant in eukaryotic cells. Three possible mechanisms may be involved in H2O2 signaling that are not mutually exclusive. In the simplest pathway, H2O2 signals through direct oxidation of the signaling protein, such as a phosphatase or a transcription factor. Although signaling proteins are frequently observed in the oxidized state in biological systems, in most cases their direct oxidation by H2O2 is too slow (10(1) M(-1)s(-1) range) to outcompete Cys-based peroxidases and glutathione. In some particular cellular compartments (such as vicinity of NADPH oxidases), it is possible that a signaling protein faces extremely high H2O2 concentrations, making the direct oxidation feasible. Alternatively, high H2O2 levels can hyperoxidize peroxiredoxins leading to local building up of H2O2 that then could oxidize a signaling protein (floodgate hypothesis). In a second model, H2O2 oxidizes Cys-based peroxidases that then through thiol-disulfide reshuffling would transmit the oxidized equivalents to the signaling protein. The third model of signaling is centered on the reducing substrate of Cys-based peroxidases that in most cases is thioredoxin. Is this model, peroxiredoxins would signal by modulating the thioredoxin redox status. More kinetic data is required to allow the identification of the complex network of thiol switches. PMID- 26813664 TI - [Not Available]. PMID- 26813665 TI - [Not Available]. PMID- 26813666 TI - Ethics requirements and impact factor in radiological journals. PMID- 26813667 TI - On the difference between evidence accumulator models and the urgency gating model. PMID- 26813668 TI - Age at Menarche and Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study Among 27,482 Women. AB - OBJECTIVE: To examine the association between age at menarche and risk of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: A prospective cohort study of 42,109 eligible pregnancies from 27,482 women in the Nurses' Health Study II. RESULTS: The adjusted risk ratios for GDM across the age at menarche categories (<=11, 12, 13, and >=14 years) were 1.34 (95% CI 1.14-1.58), 1.13 (0.97-1.31), 1.11 (0.95-1.29), and 1.00 (referent; P for trend = 0.0005), respectively. Analysis of the mediating effect indicated that 42.1% (P = 0.0007) of the association was mediated through prepregnancy BMI. CONCLUSIONS: These findings suggested that earlier menarche was significantly associated with an increased risk of GDM. This association was largely mediated through prepregnancy excessive body adiposity. PMID- 26813669 TI - Patient responses to research recruitment and follow-up surveys: findings from a diverse multicultural health care setting in Qatar. AB - BACKGROUND: Health care researchers working in the Arabian Gulf need information on how to optimize recruitment and retention of study participants in extremely culturally diverse settings. Implemented in Doha, Qatar in 2012 with 4 language groups, namely Arabic, English, Hindi, and Urdu, this research documents persons' responses to recruitment, consent, follow-up, and reminder procedures during psychometric testing of the Multicultural Assessment Instrument (MAI), a novel self- or interviewer-administered survey. METHODS: Bilingual research assistants recruited adults in outpatient clinics by approaching persons in particular who appeared to be from a target language group. Participants completed the MAI, a second acculturation instrument used for content-validity assessment, and a demographics questionnaire. Participants were asked to take the MAI again in 2-3 weeks, in person or by post, to assess test-retest reliability. Recruitment data were analyzed by using nonparametric statistics. RESULTS: Of 1503 persons approached during recruitment, 400 enrolled (27%)-100 per language group. The enrollment rates in the language groups were: Arabic-32%; English-33%; Hindi-18%; Urdu-30%. The groups varied somewhat in their preferences regarding consent procedure, follow-up survey administration, contact mode for follow-up reminders, and disclosure of personal mailing address (for postal follow-up). Over all, telephone was the preferred medium for follow-up reminders. Of 64 persons who accepted a research assistant's invitation for in-person follow-up, 40 participants completed the interview (follow-up rate, 63%); among 126 persons in the postal group with a deliverable address, 29 participants mailed back a completed follow-up survey (response rate, 23%). CONCLUSIONS: Researchers in the Arabian Gulf face challenges to successfully identify, enroll, and retain eligible study participants. Although bilingual assistants-often from the persons' own culture-recruited face-to-face, and our questionnaire contained no health care-related content, many persons were reluctant to participate. This occurrence was observed especially at follow-up, particularly among participants who had agreed to follow-up by post. PMID- 26813670 TI - Performance of ultralow-dose CT with iterative reconstruction in lung cancer screening: limiting radiation exposure to the equivalent of conventional chest X ray imaging. AB - OBJECTIVE: To investigate the detection rate of pulmonary nodules in ultralow dose CT acquisitions. MATERIALS AND METHODS: In this lung phantom study, 232 nodules (115 solid, 117 ground-glass) of different sizes were randomly distributed in a lung phantom in 60 different arrangements. Every arrangement was acquired once with standard radiation dose (100 kVp, 100 references mAs) and once with ultralow radiation dose (80 kVp, 6 mAs). Iterative reconstruction was used with optimized kernels: I30 for ultralow-dose, I70 for standard dose and I50 for CAD. Six radiologists examined the axial 1-mm stack for solid and ground-glass nodules. During a second and third step, three radiologists used maximum intensity projection (MIPs), finally checking with computer-assisted detection (CAD), while the others first used CAD, finally checking with the MIPs. RESULTS: The detection rate was 95.5 % with standard dose (DLP 126 mGy*cm) and 93.3 % with ultralow-dose (DLP: 9 mGy*cm). The additional use of either MIP reconstructions or CAD software could compensate for this difference. A combination of both MIP reconstructions and CAD software resulted in a maximum detection rate of 97.5 % with ultralow-dose. CONCLUSION: Lung cancer screening with ultralow-dose CT using the same radiation dose as a conventional chest X-ray is feasible. KEY POINTS: * 93.3 % of all lung nodules were detected with ultralow-dose CT. * A sensitivity of 97.5 % is possible with additional image post-processing. * The radiation dose is comparable to a standard radiography in two planes. * Lung cancer screening with ultralow-dose CT is feasible. PMID- 26813671 TI - Formation of microemulsions for using as cosmeceutical delivery systems: effects of various components and characteristics of some formulations. AB - Microemulsions are interesting formulations for cosmeceutical applications due to their good appearance, high solubilization power, thermodynamic stability, and enhancement of skin penetration. In addition, they can spontaneously form when suitable types and amounts of components are simply mixed. In this study, the phase behavior of the nonionic systems with various parameters was studied by construction of phase diagrams using titration method. Natural oils, i.e., coconut oil (CO), rice bran oil (RBO), and palm oil (PO), were analyzed for their fatty acid compositions and then mixed with blends of nonionic surfactants (Tween80: Span80) and water or mixtures of water and a cosolvent, propylene glycol (PG), to find the microemulsion regions. Subsequently, some microemulsions were selected for physical characterization. The largest microemulsion regions which were obtained from CO, RBO, and PO covered the sizes of 11.65, 9.84, and 9.24 %, respectively. The surfactant mixture at weight ratio of 1:1 was the most suitable for CO and PO, but for RBO, it was 2:1. PG could increase the microemulsion regions of PO from 9.24 to 15.33 %, depending on PG concentrations. Hence, the sizes of the microemulsion regions were related to oil types, surfactant mixtures, and ratios between water and PG. The studied microemulsions were water-in-oil (w/o) type, and their internal droplets were in the nanosize range. They exhibited Newtonian flow behavior and their mean viscosity values were from 247.53 to 690.35 cP which were correlated with the types and concentrations of the components in the formulations. In conclusion, natural oils could form w/o microemulsions with nonionic surfactants. The microemulsion formation and characteristics were related to many parameters of the components. PMID- 26813672 TI - Marinobacterium profundum sp. nov., a marine bacterium from deep-sea sediment. AB - A Gram-stain-negative, rod-shaped and motile strain, designated PAMC 27536T, was isolated from deep-sea sediment in the East Sea, Korea. Analysis of the 16S rRNA gene sequence of the strain showed an affiliation with the genus Marinobacterium. Phylogenetic analyses revealed that strain PAMC 27536T was related most closely to Marinobacterium rhizophilum CL-YJ9T with a 16S rRNA gene sequence similarity of 98.5 % and to other members of the genus Marinobacterium (94.0-91.7 %). Genomic relatedness analyses between strain PAMC 27536T and M. rhizophilum KCCM 42386T gave an average nucleotide identity of 85.6 % and an estimated DNA-DNA hybridization of 24.6 % using the genome-to-genome distance calculator, indicating that they represent genomically distinct species. Cells of strain PAMC 27536T grew optimally at 25-30 degrees C and pH 7.0-7.5 in the presence of 3 % (w/v) sea salts. The major cellular fatty acids were C16 : 1omega6c and/or C16 : 1omega7c, C18 : 1omega6c and/or C18 : 1omega7c, and C16 : 0. The major isoprenoid quinone was Q-8. The genomic DNA G+C content was 56.1-57.2 mol%. Based on the phylogenetic, chemotaxonomic, genomic and phenotypic data presented, a novel species with the name Marinobacterium profundum sp. nov. is proposed, with PAMC 27536T ( = KCCM 43095T = JCM 30410T) as the type strain. PMID- 26813673 TI - Effects of the physicochemical properties of gold nanostructures on cellular internalization. AB - Unique physicochemical properties of Au nanomaterials make them potential star materials in biomedical applications. However, we still know a little about the basic problem of what really matters in fabrication of Au nanomaterials which can get into biological systems, especially cells, with high efficiency. An understanding of how the physicochemical properties of Au nanomaterials affect their cell internalization is of significant interest. Studies devoted to clarify the functions of various properties of Au nanostructures such as size, shape and kinds of surface characteristics in cell internalization are under way. These fundamental investigations will give us a foundation for constructing Au nanomaterial-based biomedical devices in the future. In this review, we present the current advances and rationales in study of the relationship between the physicochemical properties of Au nanomaterials and cell uptake. We also provide a perspective on the Au nanomaterial-cell interaction research. PMID- 26813674 TI - 6-PACK programme to decrease fall injuries in acute hospitals: cluster randomised controlled trial. AB - OBJECTIVE: To evaluate the effect of the 6-PACK programme on falls and fall injuries in acute wards. DESIGN: Cluster randomised controlled trial. SETTING: Six Australian hospitals. PARTICIPANTS: All patients admitted to 24 acute wards during the trial period. INTERVENTIONS: Participating wards were randomly assigned to receive either the nurse led 6-PACK programme or usual care over 12 months. The 6-PACK programme included a fall risk tool and individualised use of one or more of six interventions: "falls alert" sign, supervision of patients in the bathroom, ensuring patients' walking aids are within reach, a toileting regimen, use of a low-low bed, and use of a bed/chair alarm. MAIN OUTCOME MEASURES: The co-primary outcomes were falls and fall injuries per 1000 occupied bed days. RESULTS: During the trial, 46 245 admissions to 16 medical and eight surgical wards occurred. As many people were admitted more than once, this represented 31 411 individual patients. Patients' characteristics and length of stay were similar for intervention and control wards. Use of 6-PACK programme components was higher on intervention wards than on control wards (incidence rate ratio 3.05, 95% confidence interval 2.14 to 4.34; P<0.001). In all, 1831 falls and 613 fall injuries occurred, and the rates of falls (incidence rate ratio 1.04, 0.78 to 1.37; P=0.796) and fall injuries (0.96, 0.72 to 1.27; P=0.766) were similar in intervention and control wards. CONCLUSIONS: Positive changes in falls prevention practice occurred following the introduction of the 6-PACK programme. However, no difference was seen in falls or fall injuries between groups. High quality evidence showing the effectiveness of falls prevention interventions in acute wards remains absent. Novel solutions to the problem of in-hospital falls are urgently needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12611000332921. PMID- 26813676 TI - Constitutive activation of Pim1 kinase is a therapeutic target for adult T-cell leukemia. AB - Human T-cell leukemia virus type 1 (HTLV-1)-associated adult T-cell leukemia and T-cell lymphoma (ATL) are aggressive diseases with poor prognoses, limited therapeutic options, and no curative treatment. In this study, we used a mouse model of ATL and restored expression of the microRNA, miR-124a, to identify in vivo downstream effectors responsible for its tumor-suppressive functions in ATL cells. Our results revealed that STAT3, a direct target of miR-124a, is constitutively activated in HTLV-I-transformed cells and ATL cells, and activating STAT3 mutations were detected in 25.5% of primary ATL patients. Interestingly, we found that the STAT3 downstream kinase effector, Pim1, is constitutively activated in ATL cells. The dependence of ATL cells to Pim1 activity was demonstrated using 2 Pim1 small inhibitors, SMI-4a and AZD1208. These studies indicated that HTLV-I-transformed and ATL cells, but not normal peripheral blood mononuclear cells, are highly sensitive to AZD1208, and the inhibition of Pim1 signaling triggers an apoptotic signal in leukemic cells. Finally, preclinical testing of AZD1208 in a mouse model of ATL resulted in significant prevention of tumor growth in vivo. In conclusion, our studies suggest that constitutive activation of the STAT3-Pim1 pathway represents a novel therapeutic target for the treatment of ATL. PMID- 26813675 TI - Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia. AB - Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is highly promising but requires robust T-cell expansion and engraftment. A T-cell defect in chronic lymphocytic leukemia (CLL) due to disease and/or therapy impairs ex vivo expansion and response to CAR T cells. To evaluate the effect of ibrutinib treatment on the T-cell compartment in CLL as it relates to CAR T-cell generation, we examined the phenotype and function of T cells in a cohort of CLL patients during their course of treatment with ibrutinib. We found that >=5 cycles of ibrutinib therapy improved the expansion of CD19-directed CAR T cells (CTL019), in association with decreased expression of the immunosuppressive molecule programmed cell death 1 on T cells and of CD200 on B-CLL cells. In support of these findings, we observed that 3 CLL patients who had been treated with ibrutinib for >=1 year at the time of T-cell collection had improved ex vivo and in vivo CTL019 expansion, which correlated positively together and with clinical response. Lastly, we show that ibrutinib exposure does not impair CAR T cell function in vitro but does improve CAR T-cell engraftment, tumor clearance, and survival in human xenograft models of resistant acute lymphocytic leukemia and CLL when administered concurrently. Our collective findings indicate that ibrutinib enhances CAR T-cell function and suggest that clinical trials with combination therapy are warranted. Our studies demonstrate that improved T-cell function may also contribute to the efficacy of ibrutinib in CLL. These trials were registered at www.clinicaltrials.gov as #NCT01747486, #NCT01105247, and #NCT01217749. PMID- 26813677 TI - Effects of G.H.3. On mental symptoms and health-related quality of life among older adults: results of a three-month follow-Up study in Shanghai, China. AB - OBJECTIVE: To explore the effects of daily use of Gerovital H3 (G.H.3.) tablets on relieving mental symptoms and improving health-related quality of life among Chinese older adults population. METHODS: In a randomized, placebo-controlled, double-blinded study, totally 100 eligible participants were randomly allocated into the G.H.3. group or the placebo group, administered either G.H.3. or placebo tablets and were followed up for three months. All of the participants were required to report their subjective feelings about quality of life, low mood, and anxiety by filling out Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS) and a 36-item Short-Form Health Survey (SF-36 scale). Physicians were responsible for evaluating the related mental health indications through physical examinations at the baseline and at the end of the intervention period. RESULTS: Participants were men and women between 50 and 89 years of age, with a median of 62.53 years. Before the intervention, the demographic characteristics and the baseline SF-36 scores, low mood, and anxiety statuses were comparable (p > 0.05). After the 12-week intervention, the scores of role-physical (RP), bodily pain (BP), general health (GH), vitality (VT), mental health (MH) and health transition (HT), mental composite score (MCS) of the G.H.3. group were higher than the placebo group (p < 0.05), There were no significant differences in other domains in SF-36 and PCS between the two groups(p > 0.05), the scores of SDS and SAS in the G.H.3. group were both lower than the placebo group(p < 0.01), the prevalence rates of low moods in the G.H.3. group and the placebo group were 20.8 % and 34.0 % respectively, no significant difference was found (chi (2) =2.127,p = 0.145), while the prevalence rate of clinical anxiety concerns in the G.H.3. group was 2.1 %, which was significantly lower than the placebo group, 22.0 % (chi (2) =9.040,p < 0.001). CONCLUSIONS: Preliminarily use of G.H.3. shows positive effects in supporting mental health and improving general health and well-being while promoting the recovery of cognitive function among older adults. Most of SF-36 domains including PF, RP, BP, GH, VT, RE, MH, and HT, as well as the overall quality of life in MCS might benefit from taking G.H.3. tablets. Average levels of low moods and anxiety concerns were both reduced and the prevalence rate of clinical anxiety concerns were reduced. PMID- 26813678 TI - The enigma of men with interstitial cystitis/bladder pain syndrome. AB - Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common and frequently misdiagnosed disorder in men. Hallmark symptoms are the presence of chronic discomfort attributed to the urinary bladder associated with bladder filling and relieved with bladder emptying, often associated with irritative voiding symptoms, in the absence of any other identifiable cause. It is often grouped with another common clinical entity, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Men with IC/BPS often suffer from a delay in diagnosis and subsequent treatment, often being categorized as having prostatitis, benign prostatic hyperplasia, or epididymitis before the correct diagnosis is reached. The etiology of IC/BPS is poorly understood, and its pathogenesis may involve multiple pathways leading to a common clinical entity. Diagnostic criteria continue to evolve over time as the understanding of IC/BPS improves, and a clinical diagnosis with properly performed history and physical exam is suitable for diagnosis after other processes such as infection, radiation, or pharmaceutical exposure are appropriately excluded. No set pathological findings, biomarkers, or phenotypic descriptions have been universally accepted as a result of conflicting studies. Guidelines for diagnostic and treatment options are limited by available data, and few studies incorporate substantial numbers of male patients. Reported outcomes for common therapies are mixed or have not yet been subjected to study in rigorous placebo-controlled clinical trials in men. Lessons learned from the treatment of CP/CPPS can be applied to IC/BPS, by favoring a phenotypically directed, multimodal approach rather than a stepwise algorithm as advocated by current practice guidelines. PMID- 26813680 TI - Impact of Health Literacy, Self-efficacy, and Outcome Expectations on Adherence to Self-care Behaviors in Iranians with Type 2 Diabetes. AB - OBJECTIVES: Diabetic patients with higher health literacy (HL) may feel more confident in their ability to perform self-care behaviors and may have strong beliefs that diabetes-related behaviors will lead to specific outcomes. Our study aimed to document the relationships between HL, self-efficacy, outcome expectations, and diabetes self-care of patients with type 2 diabetes mellitus (T2DM) in Iran. METHODS: We conducted a cross-sectional observational study of 187 patients with T2DM. Participants completed the Functional Communicative and Critical Health Literacy scale, the Summary of Diabetes Self-Care Activities, the Diabetes Management Self-Efficacy Scale, Outcome Expectations Questionnaire, and a demographic questionnaire. RESULTS: Participants who received diabetes education (t = 5.79, p<0.001) and were married (F = 3.04, p<0.050) had better diabetes self-care behavior. There was a significant positive correlation between self-care behaviors and communicative HL (r = 0.455, p<0.010), critical HL (r = 0.297, p<0.010), self-efficacy (r = 0.512, p<0.010) and outcome expectations (r = 0.387, p<0.010). Diabetes education and marital status accounted for 16.9% of the variance in diabetes self-care. Self-efficacy, outcome expectations, communicative, and critical HL explained 28.0%, 1.5%, 3.7%, and 1.4% of the variance, respectively. CONCLUSIONS: This study revealed that the potential impact of self-efficacy, outcome expectations, communicative, and critical HL should be considered in the education program for patients with diabetes. We found self-efficacy to be the most important predictor of diabetes self-care. Therefore, the use of self-efficacy theory when designing patient education interventions could enhance diabetes self-care. It is essential that health care providers assess patient's HL levels to tailor health-related information specific to a domain of HL. This would fully inform patients and promote empowerment rather than simple compliance. PMID- 26813679 TI - Evolutionary and developmental implications of asymmetric brain folding in a large primate pedigree. AB - Bilateral symmetry is a fundamental property of the vertebrate central nervous system. Local deviations from symmetry provide various types of information about the development, evolution, and function of elements within the CNS, especially the cerebral hemispheres. Here, we quantify the pattern and extent of asymmetry in cortical folding within the cerebrum of Papio baboons and assess the evolutionary and developmental implications of the findings. Analyses of directional asymmetry show a population-level trend in length measurements indicating that baboons are genetically predisposed to be asymmetrical, with the right side longer than the left in the anterior cerebrum while the left side is longer than the right posteriorly. We also find a corresponding bias to display a right frontal petalia (overgrowth of the anterior pole of the cerebral cortex on the right side). By quantifying fluctuating asymmetry, we assess canalization of brain features and the susceptibility of the baboon brain to developmental perturbations. We find that features are differentially canalized depending on their ontogenetic timing. We further deduce that development of the two hemispheres is to some degree independent. This independence has important implications for the evolution of cerebral hemispheres and their separate specialization. Asymmetry is a major feature of primate brains and is characteristic of both brain structure and function. PMID- 26813681 TI - Characterization of halo-alkaline and thermostable protease from Halorubrum ezzemoulense strain ETR14 isolated from Sfax solar saltern in Tunisia. AB - A total of 54 halophilic strains were isolated from crystallizer TS18 (26 strains) and non-crystallizer M1 (28 strains) ponds and screened for their ability to produce protease, amylase, and lipase activities. Enzymatic assays allowed the selection of thirty-two active strains, among them, the ETR14 strain from TS18 showed maximum protease production yields and therefore, selected for further analysis. The results from 16S rRNA gene sequence analysis revealed that the strain belonged to Halorubrum ezzemoulense (Hrr. ezzemoulense) species. Further results indicated that optimum growth and protease production yields were obtained with 10-15% NaCl concentrations in the DSC-97 medium. The enzyme was also able to maintain high levels of protease activity at salt concentrations of up to 25%. While readily available carbon sources were noted to significantly reduce protease production, the combination between yeast extract and peptone enhanced protease excretion, which reached a maximum of 284 U ml(-1) at the end of the exponential growth phase. The enzyme exhibited optimum activity at pH 9 and 60 degrees C. The halophilic protease retained 87% of its initial activity after 1 h incubation at 70 degrees C and showed high stability over a wide range of pH, ranging from 7 to 10. This protease exhibited good temperature, pH, and salinity tolerance, which distinguishes it from other proteases previously described from other members of the holoarchaea genera and makes it a promising candidate for application in various industries. PMID- 26813682 TI - A Mobile Phone App to Stimulate Daily Physical Activity in Patients with Chronic Obstructive Pulmonary Disease: Development, Feasibility, and Pilot Studies. AB - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) demonstrate reduced levels of daily physical activity (DPA) compared to healthy controls. This results in a higher risk of hospital admission and shorter survival. Performing regular DPA reduces these risks. OBJECTIVE: To develop an eHealth intervention that will support patients with COPD to improve or maintain their DPA after pulmonary rehabilitation. METHODS: The design process consisted of literature research and the iterative developing and piloting phases of the Medical Research Council (MRC) model for complex clinical interventions and the involvement of end users. Participants were healthy adults and persons with COPD. RESULTS: The mobile phone interface met all the set requirements. Participants found that the app was stimulating and that reaching their DPA goals was rewarding. The mean (SD) scores on a 7-point scale for usability, ease of use, ease of learning, and contentment were 3.8 (1.8), 5.1 (1.1), 6.0 (1.6), and 4.8 (1.3), respectively. The mean (SD) correlation between the mobile phone and a validated accelerometer was 0.88 (0.12) in the final test. The idea of providing their health care professional with their DPA data caused no privacy issues in the participants. Battery life lasted for an entire day with the final version, and readability and comprehensibility of text and colors were favorable. CONCLUSIONS: By employing a user-centered design approach, a mobile phone was found to be an adequate and feasible interface for an eHealth intervention. The mobile phone and app are easy to learn and use by patients with COPD. In the final test, the accuracy of the DPA measurement was good. The final version of the eHealth intervention is presently being tested by our group for efficacy in a randomized controlled trial in COPD patients. PMID- 26813683 TI - Couples-based interventions following prostate cancer treatment: a narrative review. AB - BACKGROUND: Sexual dysfunction following prostate cancer (PC) treatment often results in sexual avoidance and a loss of sexual intimacy, which can lead to relationship distress. This review aims to evaluate six studies intended to address relational and sexual intimacy following PC treatment and discuss methodological concerns which may help produce more effective interventions. METHODS: Electronic databases used to conduct literature searches included Medline, PsychINFO, and Web of Science. Studies were included if they were: randomized controlled trials (RCTs) using samples of men diagnosed with PC of any stage, had a psychosocial intervention, and addressed at least one sexual and relational outcome. RESULTS: As a whole, the literature has produced mixed results. While significant findings were reported, many of the primary hypotheses were not achieved. The six studies show that men with PC may benefit from education and support related to treatment options for erectile dysfunction (ED), whereas their partners may benefit more from interventions focused on relational issues. Important methodological limitations included: selection of general outcome measures as opposed to measures specific to sexuality or intimacy outcomes, lack of assessing distress or bother of the patient/couples as study entry criteria, heterogeneity of study populations, and lack of innovative intervention content as the current studies tested standard educational interventions, sex therapies techniques, and couples therapy strategies with only marginal success. CONCLUSIONS: Interventions based on innovative theoretical approaches as well as study designs that address the outlined methodological limitations are needed in this area. PMID- 26813684 TI - Activity Enhancement of G-Quadruplex/Hemin DNAzyme by Flanking d(CCC). AB - G-quadruplex (G4)/hemin DNAzymes have been extensively applied in bioanalysis and molecular devices. However, their catalytic activity is still much lower than that of proteinous enzymes. The G4/hemin DNAzyme activity is correlated with the G4 conformations and the solution conditions. However, little is known about the effect of the flanking sequences on the activity, though they are important parts of G4s. Here, we report sequences containing d(CCC), flanked on both ends of the G4-core sequences remarkably enhance their DNAzyme activity. By using circular dichroism and UV-visible spectroscopy, the d(CCC) flanking sequences were demonstrated to improve the hemin binding affinity to G4s instead of increasing the parallel G4 formation, which might explain the enhanced DNAzyme activity. Meanwhile, the increased hemin binding ability promoted the degradation of hemin within the DNAzyme by H2O2. Furthermore, the DNAzyme with d(CCC) flanking sequences showed strong tolerance to pH value changes, which makes it more suitable for applications requiring wide pH conditions. The results highlight the influence of the flanking sequences on the DNAzyme activity and provide insightful information for the design of highly active DNAzymes. PMID- 26813685 TI - Identification of Potent Virtual Leads Specific to S1' Loop of ADAMTS4: Pharmacophore Modeling, 3D-QSAR, Molecular Docking and Dynamic Studies. AB - ADAMTS4 (Aggrecanase-1) is an important enzyme, which belongs to ADAMTS family. Aggrecanase-1 is involved in aggrecan degradation of articular cartilage in osteoarthritis and rheumatoid arthritis. Overall variability of S1' domain of ADAMTS4 has been the main selectivity determinant to design the unique inhibitors. 34 inhibitors from Binding database and literature were used to develop the pharmacophore model. The five featured pharmacophore model AHHRR had the best survival score of 3.493 and post-hoc score of 2.545, indicating that the model is highly reliable. The 3D-QSAR acquired had excellent r(2) value of 0.99 and GH score of 0.839. The validated pharmacophore model was used for insilico screening of Asinex and ZINC database for finding the potential lead compounds. ZINC00987406 and ASN04459656 which pose high glide score i.e >7 Kcal/mol and H bond and hydrophobic interactions in the S1'loop residues of ADAMTS4 were subjected to Molecular Dynamics Simulation studies. Molecular dynamic simulation result indicates that the RMSD and RMSF of backbone atoms for the above complexes were within the limit of 2.0 A. These compounds can be potential candidates for osteoarthritis by inhibiting ADAMTS4. PMID- 26813686 TI - Designing string-of-beads vaccines with optimal spacers. AB - String-of-beads polypeptides allow convenient delivery of epitope-based vaccines. The success of a polypeptide relies on efficient processing: constituent epitopes need to be recovered while avoiding neo-epitopes from epitope junctions. Spacers between epitopes are employed to ensure this, but spacer selection is non trivial.We present a framework to determine optimally the length and sequence of a spacer through multi-objective optimization for human leukocyte antigen class I restricted polypeptides. The method yields string-of-bead vaccines with flexible spacer lengths that increase the predicted epitope recovery rate fivefold while reducing the immunogenicity from neo-epitopes by 44% compared to designs without spacers. PMID- 26813687 TI - [Rheumatism and cancer]. PMID- 26813688 TI - [Malignancies of the skin and immunomodulatory antirheumatic therapy]. AB - For the clinical practice there is uncertainty as to what degree the therapeutic immunomodulation of rheumatoid arthritis (RA) is associated with a weakening of protective tumor immunity. Neoplasms of the skin in particular are known to exhibit increased incidence rates in association with therapeutic immunosuppression in transplantation medicine; however, the immunosuppression required for the prevention of allogenic graft rejection is much more intensive and thus not directly transferable to the potential risks for an onset or relapse of melanoma or non-melanoma skin cancers (NMSC), e. g. spinocellular and basal cell carcinomas in association with the antirheumatic treatment of RA. This review covers the association of RA and its pharmacotherapy with conventional synthetic (cs) and biologic disease-modifying antirheumatic drugs (DMARD) on the basis of a systematic literature search. The incidence rates of NMSC are twice as high in biologic-naive RA patients compared to the general population, whereas the respective incidence rates for melanoma do not differ. A biologic treatment with tumor necrosis factor (TNF) blockers compared with administration of csDMARD only has a minor, if any effect on the increase of NMSC risk but is associated with a trend towards an elevated incidence rate of new onset melanoma although significance level was not reached in all of the reviewed studies. The data on non-TNF blocking biologics is sparse. Accordingly, it is inappropriate to draw any strong conclusions on potentially associated skin cancer risks from the present lack of safety signals. The consideration of individual risk factors, recommendations on sufficient UV protection and regular skin monitoring may serve to improve the safety of DMARD therapy in RA. PMID- 26813689 TI - [Gynecological cancers in patients with inflammatory rheumatic diseases]. AB - The risk of gynecological cancers in patients with inflammatory rheumatic diseases only seems to be elevated with respect to cervical cancer and mainly in patients with systemic lupus erythematosus. There is increasing evidence for an influence of the immune system on tumor control of gynecological malignancies; however, an adverse influence of immunosuppressive treatment in rheumatic patients was indicated only for the risk of cervical cancer. In contrast, biologics could not be shown to cause an increased risk of cervical cancer but data on this topic are limited. General screening recommendations exist for breast cancer and cervical cancer. Recommendations for follow-up after oncological treatment are presented. Because of limited evidence immunosuppressive and biological treatment should be applied with great restraint at least within the first 5 years after curative oncological treatment also for gynecological tumors. As far as breast cancer is concerned an even longer interval is under discussion. PMID- 26813690 TI - New small-size peptides modulators of the exosite of BACE1 obtained from a structure-based design. AB - We report here two new small-size peptides acting as modulators of the beta-site APP cleaving enzyme 1 (BACE1) exosite. Ac-YPYFDPL-NH2 and Ac-YPYDIPL-NH2 displayed a moderate but significant inhibitory effect on BACE1. These peptides were obtained from a molecular modeling study. By combining MD simulations with ab initio and DFT calculations, a simple and generally applicable procedure to evaluate the binding energies of small-size peptides interacting with the exosite of the BACE1 is reported here. The structural aspects obtained for the different complexes were analyzed providing a clear picture about the binding interactions of these peptides. These interactions have been investigated within the framework of the density functional theory and the quantum theory of atoms in molecules using a reduced model. Although the approach used here was traditionally applied to the study of noncovalent interactions in small molecules complexes in gas phase, we show, through in this work, that this methodology is also a very powerful tool for the study of biomolecular complexes, providing a very detailed description of the binding event of peptides modulators at the exosite of BACE1. PMID- 26813691 TI - Rebinding dynamics of NO to microperoxidase-8 probed by time-resolved vibrational spectroscopy. AB - Femtosecond vibrational spectroscopy was used to probe the rebinding kinetics of NO to microperoxidase-8 (Mp), an ideal model system for the active site of ligand binding heme proteins, including myoglobin and hemoglobin, after the photodeligation of MpNO in glycerol/water (G/W) solutions at 294 K. The geminate rebinding (GR) of NO to Mp in viscous solutions was highly efficient and ultrafast and negligibly dependent on the solution viscosity, which was adjusted by changing the glycerol content from 65% to 90% by volume in G/W mixtures. The kinetics of the GR of NO to Mp in viscous solutions was well represented by an exponential function with a time constant of ca. 11 ps. Although the kinetic traces of the GR of NO to Mp in solutions with three different viscosities (18, 81, and 252 cP) almost overlap, they show a slight difference early in the decay process. The kinetic traces were also described by the diffusion-controlled reaction theory with a Coulomb potential. Since the ligand is deligated in a neutral form, an ionic pair of NO(-) and Mp(+) may be produced before forming the Mp-NO bond by an electron transfer from Mp to NO as the deligated NO is sufficiently near to the Fe atom of Mp. The strong reactivity between NO and ferrous heme may arise from the Coulomb interaction between the reacting pair, which is consistent with the harpooning mechanism for NO binding to heme. PMID- 26813692 TI - Relationship Between the Parenting Styles and Students' Educational Performance Among Iranian Girl High School Students, A Cross- Sectional Study. AB - INTRODUCTION: Parenting styles are effective in the educational performance of their child. The present study aimed to investigate the relationship between the parenting styles and students' educational performance among Iranian girl high school students. MATERIALS AND METHODS: In a cross-sectional survey, female students in high schools of Ilam (Iran) evaluated during the academic year 2014 15. Multistage cluster random sampling was used to select the participants. Data were collected by two demographic and Baumrind's parenting styles questionnaire. The Cronbach's alpha coefficient was measured as an index of internal identicalness of the questionnaire to verify its reliability. RESULTS: A total 400 students were studied. The Mean+/-SD of the students' age were 14+/-1.08. The students' school grades were the first year of high school to pre-university course. The Mean+/-SD of parenting styles were 35.37+/-5.8, 34.69+/-6.34 and 19.17+/-6.64 for permissive parenting style, authoritarian parenting style and authoritative parenting styles, respectively. There was a significant relationship between the score of permissive parenting style (p= 0.001, r= 0.151), authoritarian parenting style (p= 0.001, r= 0.343) and authoritative parenting style (p=0. 001, r= 0.261) with the students' average score for studying. CONCLUSION: The results of this study demonstrate that parental influence plays an important role in students' educational performance. PMID- 26813693 TI - Characterization of the Enzymatic Activity of SETDB1 and Its 1:1 Complex with ATF7IP. AB - The protein methyltransferase (PMT) SETDB1 is a strong candidate oncogene in melanoma and lung carcinomas. SETDB1 methylates lysine 9 of histone 3 (H3K9), utilizing S-adenosylmethionine (SAM) as the methyl donor and its catalytic activity, has been reported to be regulated by a partner protein ATF7IP. Here, we examine the contribution of ATF7IP to the in vitro activity and substrate specificity of SETDB1. SETDB1 and ATF7IP were co-expressed and 1:1 stoichiometric complexes were purified for comparison against SETDB1 enzyme alone. We employed both radiometric flashplate-based and SAMDI mass spectrometry assays to follow methylation on histone H3 15-mer peptides, where lysine 9 was either unmodified, monomethylated, or dimethylated. Results show that SETDB1 and the SETDB1:ATF7IP complex efficiently catalyze both monomethylation and dimethylation of H3K9 peptide substrates. The activity of the binary complex was 4-fold lower than SETDB1 alone. This difference was due to a decrease in the value of kcat as the substrate KM values were comparable between SETDB1 and the SETDB1:ATF7IP complex. H3K9 methylation by SETDB1 occurred in a distributive manner, and this too was unaffected by the presence of ATF7IP. This finding is important as H3K9 can be methylated by HMTs other than SETDB1 and a distributive mechanism would allow for interplay between multiple HMTs on H3K9. Our results indicate that ATF7IP does not directly modulate SETDB1 catalytic activity, suggesting alternate roles, such as affecting cellular localization or mediating interaction with additional binding partners. PMID- 26813694 TI - Shifts in target modality cause attentional reset: Evidence from sequential modulation of crossmodal congruency effects. AB - Reduced congruency effects after a preceding incongruent trial suggest a conflict monitoring process, which reactively triggers the recruitment of attentional control in subsequent trials. In the present study, we assessed this sequential modulation of crossmodal congruency effects separately in two different tasks. Participants performed a location judgment task and a numerical judgment task in a block-wise fashion in a modality-switching paradigm. Stimuli were presented simultaneously in two modalities and were either congruent or incongruent (e.g., left visual object, right sound) with each other. The target modality was indicated by a cue, so that the target modalities either repeated or switched in successive trials. For both tasks, the results indicated reduced congruency effects after an incongruent trial only for modality repetitions, but not for switches. This finding suggests that modality switches induce a shift in episodic context, which in turn leads to an attentional reset. This reset eliminates the sequential modulation of congruency effects. PMID- 26813696 TI - Erwinia gerundensis sp. nov., a cosmopolitan epiphyte originally isolated from pome fruit trees. AB - A survey to obtain potential antagonists of pome fruit tree diseases yielded two yellow epiphytic bacterial isolates morphologically similar to Pantoea agglomerans, but showing no biocontrol activity. Whole-cell MALDI-TOF mass spectrometry and analysis of 16S rRNA gene and gyrB sequences suggested the possibility of a novel species with a phylogenetic position in either the genus Pantoea or the genus Erwinia. Multi-locus sequence analysis (MLSA) placed the two strains in the genus Erwinia and supported their classification as a novel species. The strains showed general phenotypic characteristics typical of this genus and results of DNA-DNA hybridizations confirmed that they represent a single novel species. Both strains showed a DNA G+C content, as determined by HPLC, of 54.5 mol% and could be discriminated from phylogenetically related species of the genus Erwinia by their ability to utilize potassium gluconate, potassium 2-ketogluconate, maltose, melibiose and raffinose. Whole-genome sequencing of strain EM595T revealed the presence of a chromosomal carotenoid biosynthesis gene cluster similar to those found in species of the genera Cronobacter and Pantoea that explains the pigmentation of the strain, which is atypical for the genus Erwinia. Additional strains belonging to the same species were recovered from different plant hosts in three different continents, revealing the cosmopolitan nature of this epiphyte. The name Erwinia gerundensis sp. nov. is proposed, with EM595T ( = LMG 28990T = CCOS 903T) as the designated type strain. PMID- 26813695 TI - Autologous skeletal muscle derived cells expressing a novel functional dystrophin provide a potential therapy for Duchenne Muscular Dystrophy. AB - Autologous stem cells that have been genetically modified to express dystrophin are a possible means of treating Duchenne Muscular Dystrophy (DMD). To maximize the therapeutic effect, dystrophin construct needs to contain as many functional motifs as possible, within the packaging capacity of the viral vector. Existing dystrophin constructs used for transduction of muscle stem cells do not contain the nNOS binding site, an important functional motif within the dystrophin gene. In this proof-of-concept study, using stem cells derived from skeletal muscle of a DMD patient (mdcs) transplanted into an immunodeficient mouse model of DMD, we report that two novel dystrophin constructs, C1 (DeltaR3-R13) and C2 (DeltaH2 R23), can be lentivirally transduced into mdcs and produce dystrophin. These dystrophin proteins were functional in vivo, as members of the dystrophin glycoprotein complex were restored in muscle fibres containing donor-derived dystrophin. In muscle fibres derived from cells that had been transduced with construct C1, the largest dystrophin construct packaged into a lentiviral system, nNOS was restored. The combination of autologous stem cells and a lentivirus expressing a novel dystrophin construct which optimally restores proteins of the dystrophin glycoprotein complex may have therapeutic application for all DMD patients, regardless of their dystrophin mutation. PMID- 26813697 TI - Alignment and Patterning of Ordered Small-Molecule Organic Semiconductor Micro /Nanocrystals for Device Applications. AB - Large-area alignment and patterning of small-molecule organic semiconductor micro /nanocrystals (SMOSNs) at desired locations is a prerequisite for their practical device applications. Recent strategies for alignment and patterning of ordered SMOSNs and their corresponding device applications are highlighted. PMID- 26813698 TI - Cytoplasmic Determination of Meiotic Spindle Size Revealed by a Unique Inter Species Germinal Vesicle Transfer Model. AB - Spindle sizes are different in diverse species and cell types. In frogs, the meiotic spindle size is positively correlated with the egg cell volume. Across species, relatively small mouse oocytes (70-80 MUm) have a relatively large spindle while larger pig oocytes (about 120 MUm) have a considerably smaller spindle. In this study we investigated whether species-specific oocyte spindle size was determined by cytoplasmic or nuclear factors. By exchanging the germinal vesicle between mouse and pig oocytes, we obtained two kinds of reconstructed oocytes: one with mouse ooplasm and pig GV (mCy-pGV oocyte), and the other with pig ooplasm and mouse GV (pCy-mGV oocyte). We show that the MII spindle size of the mCy-pGV oocyte is similar to that of the mouse meiotic spindle and significantly larger than that of the pig meiotic spindle. The timing of oocyte maturation also followed that of the species from which the oocyte cytoplasm arose, although some impact of the origin of the GV was observed. These data suggest that spindle size and the timing of meiotic progression are governed by cytoplasmic components rather than cytoplasmic volume and GV materials. PMID- 26813699 TI - A comparative study on psycho-socio-demographic and clinical profile of patients with bipolar versus unipolar depression. AB - BACKGROUND: Several studies have revealed significant differences between bipolar (BP) and unipolar depression (UP). Misdiagnosing BP depression results in suboptimal symptom resolution, induction of manic switch, mixed state, or accelerated cycling. This study compares various psycho-socio-demographic, longitudinal course, and phenomenological factors associated with BP and UP depression. MATERIALS AND METHODS: We compared 30 UP and 30 BP depression patients using a specially designed intake proforma, International Classification of Diseases-10 diagnostic criteria for research, Hamilton Rating Scale for Depression-21 (HAMD-21), Hypomania Checklist-32 Questionnaire (HCL-32), Brief psychiatric rating scale (BPRS), and Kuppuswami's socioeconomic status scale. RESULTS: BP depression group consisted of mostly males, with earlier age of onset of illness, longer illness duration, frequent episodes, hospitalizations and psychotic symptoms. The total HAM-D score and 4 HAM-D item scores-psychomotor retardation, insight, diurnal variation of symptoms and its severity, and paranoid symptoms were significantly higher in this group. Binary logistic regression identified the age of onset, the total duration of illness, frequency of affective episodes, and presence of delusions as predictors of bipolarity (odds ratio = 1.327; 1.517; 0.062; 0.137). CONCLUSIONS: Identification of clinical markers of bipolarity from large scale prospective studies is needed. PMID- 26813700 TI - Child-specific food insecurity and its sociodemographic and nutritional determinants among Iranian schoolchildren. AB - Despite strong evidence of the prevalence of food insecurity in adults and households with children in different areas of Iran, the prevalence of child specific food insecurity in Iran and especially in Tabriz has not been evaluated. Therefore, the objective of the current study is to evaluate the prevalence of food insecurity in schoolchildren and to identify its social, demographic, and nutritional determinants in Tabriz, Iran. This cross-sectional study was conducted between April and September 2014 among 330 schoolchildren aged 7-11 years comprising 170 boys and 160 girls from ten public schools in Tabriz, Iran. Demographic and socioeconomic factors had been obtained from participants. Food security status was assessed by an eight-item U.S. Department of Agriculture (USDA) Food Security Module previously validated for use in Iran. Dietary information was obtained by a food frequency questionnaire (FFQ). In our findings, the prevalence of food insecurity among children was 30% with 29.1% being low food secure and 0.9% being very low food secure. Mean weight for age Z score (WAZ) in the food insecure group was significantly lower than in the food secure group. The prevalence of food insecurity was more prevalent in boys (p = .006). Food insecure children had a significantly lower intake of energy, carbohydrate, protein, and meat (p < .001) and higher prevalence of wasting compared with their counterparts in the food secure group (p = .004). These results suggest a proportionally high prevalence of food insecurity in schoolchildren in Tabriz and its significant association with poor nutritional status and dietary habits. Our findings also ensures the necessity of nutritional support programs and nutritional education in Iranian low-income families to improve their overall health. PMID- 26813701 TI - Analysis of breast milk fatty acid composition using dried milk samples. AB - BACKGROUND: The effect of breast milk fatty acid (FA) composition, particularly levels of docosahexaenoic acid (DHA), on infant health outcomes is unclear. Part of the reason for this is difficulties in collecting, storing and shipping milk samples to the laboratory. Here we report the validation of a dried milk spot (DMS) system to measure FA composition to help overcome these obstacles. Milk FA were measured by gas chromatography and reported as percent of total FA; the FA of primary interest in this study were DHA and industrially produced trans FA (iTFA). Experiments were carried out using pooled milk samples from US (n = 5) and Malawian women (n = 50). Experiments compared liquid vs. DMS samples (n = 55), assessed stability of FA composition under different storage conditions (n = 5), and compared the results from two different labs using the same methods (n = 5). RESULTS: Both % DHA and % iTFA levels in liquid and DMS samples were strongly correlated (R(2) = 0.99 and 0.99, respectively, P < 0.0001). The % DHA in DMS samples was stable for up to four weeks at room temperature and up to three years at -80 degrees C; only slight deviations from the acceptable range of variability (+/-15 %) occurred in the 4 degrees C and -20 degrees C conditions for % DHA. The % iTFA was stable under all conditions. All % DHA and % iTFA were within 15 % of the referent when analyzed in two laboratories. CONCLUSIONS: Valid FA composition values can be obtained from DMS samples using this robust collection and transport system which should facilitate studies of the role of milk FA composition in infant development. PMID- 26813702 TI - Fate of Fusarium Toxins during the Malting Process. AB - Little is known about the fate of Fusarium mycotoxins during the barley malting process. To determine the fungal DNA and mycotoxin concentrations during malting, we used barley grain harvested from field plots that we had inoculated with Fusarium species that produce type A or type B trichothecenes or enniatins. Using a recently developed multimycotoxin liquid chromatography-tandem mass stable isotope dilution method, we identified Fusarium-species-specific behaviors of mycotoxins in grain and malt extracts and compared toxin concentrations to amounts of fungal DNA in the same samples. In particular, the type B trichothecenes and Fusarium culmorum DNA contents were increased dramatically up to 5400% after kilning. By contrast, the concentrations of type A trichothecenes and Fusarium sporotrichioides DNA decreased during the malting process. These data suggest that specific Fusarium species that contaminate the raw grain material might have different impacts on malt quality. PMID- 26813703 TI - Historical photographs revisited: A case study for dating and characterizing recent loss of coral cover on the inshore Great Barrier Reef. AB - Long-term data with high-precision chronology are essential to elucidate past ecological changes on coral reefs beyond the period of modern-day monitoring programs. In 2012 we revisited two inshore reefs within the central Great Barrier Reef, where a series of historical photographs document a loss of hard coral cover between c.1890-1994 AD. Here we use an integrated approach that includes high-precision U-Th dating specifically tailored for determining the age of extremely young corals to provide a robust, objective characterisation of ecological transition. The timing of mortality for most of the dead in situ corals sampled from the historical photograph locations was found to coincide with major flood events in 1990-1991 at Bramston Reef and 1970 and 2008 at Stone Island. Evidence of some recovery was found at Bramston Reef with living coral genera similar to what was described in c.1890 present in 2012. In contrast, very little sign of coral re-establishment was found at Stone Island suggesting delayed recovery. These results provide a valuable reference point for managers to continue monitoring the recovery (or lack thereof) of coral communities at these reefs. PMID- 26813704 TI - Differential diagnosis between primary lung squamous cell carcinoma and pulmonary metastasis of head and neck squamous cell carcinoma. AB - Differentiation between lung squamous cell carcinoma and pulmonary metastasis of head and neck squamous cell carcinoma is clinically important because the prognoses and therapeutic options are considerably different. However, the clinical, pathological, and immunohistochemical diagnostic methods have not yet been fully established. Although various molecular methods have been developed, they have not yet been practically applied. A combined approach involving molecular and immunohistochemical analysis, such as one that uses antibodies selected on the basis of comprehensive genetic analysis results, may be effective. We suggest a new diagnostic criteria using the clinical characteristics and the result of immunohistochemical analysis. However, there are two underlying problems in the development of new diagnostic methods: tumor heterogeneity and determination of the diagnostic accuracy. PMID- 26813705 TI - Effect of the interaction between childhood abuse and rs1360780 of the FKBP5 gene on gray matter volume in a general population sample. AB - OBJECTIVE: The FKBP5 gene codes for a co-chaperone that regulates glucocorticoid receptor sensitivity and thereby impacts the reactivity of the hypothalamic pituitary-adrenal (HPA)-axis. Evidence suggested that subjects exposed to childhood abuse and carrying the TT genotype of the FKBP5 gene single nucleotide polymorphism (SNP) rs1360780 have an increased susceptibility to stress-related disorders. METHOD: The hypothesis that abused TT genotype carriers show changes in gray matter (GM) volumes in affect-processing brain areas was investigated. About 1,826 Caucasian subjects (age <= 65 years) from the general population [Study of Health in Pomerania (SHIP)] in Germany were investigated. The interaction between rs1360780 and child abuse (Childhood Trauma Questionnaire) and its effect on GM were analyzed. RESULTS: Voxel-based whole-brain interaction analysis revealed three large clusters (FWE-corrected) of reduced GM volumes comprising the bilateral insula, the superior and middle temporal gyrus, the bilateral hippocampus, the right amygdala, and the bilateral anterior cingulate cortex in abused TT carriers. These results were not confounded by major depressive disorders. In region of interest analyses, highly significant volume reductions in the right hippocampus/parahippocampus, the bilateral anterior and middle cingulate cortex, the insula, and the amygdala were confirmed in abused TT carriers compared with abused CT/CC carriers. CONCLUSION: The results supported the hypothesis that the FKBP5 rs1360780 TT genotype predisposes subjects who have experienced childhood abuse to widespread structural brain changes in the subcortical and cortical emotion-processing brain areas. Those brain changes might contribute to an increased vulnerability of stress-related disorders in TT genotype carriers. PMID- 26813706 TI - A comparative study of the clinical efficacy and safety of agomelatine with escitalopram in major depressive disorder patients: A randomized, parallel-group, phase IV study. AB - OBJECTIVE: To compare the efficacy of agomelatine with escitalopram in the treatment of major depressive disorder (MDD), improve sleep in MDD patients and study the adverse effects of agomelatine. MATERIALS AND METHODS: Randomized, parallel-group, open-label study. The primary efficacy outcome was change from baseline to last post-baseline value in Hamilton depression rating scale and Leeds sleep evaluation questionnaire scale. Both parametric and nonparametric tests were applied for analysis. RESULTS: Within-group and between-groups comparison of the mean HAMD17 scores showed statistically significant changes (P < 0.0001). Escitalopram showed early onset of response and remission compared to agomelatine at 10(th) week (P < 0.0001) and 14(th) week (P < 0.0001), respectively. In agomelatine, within-group and between-groups change of the mean LSEQ score was statistically significant at subsequent follow-up visits (P < 0.0001). CONCLUSION: Escitalopram is superior to agomelatine in efficacy, considering the early response, early remission, and better relief from symptoms of MDD in adults. Agomelatine may be preferred in MDD patients having insomnia as a predominant symptom. Liver function monitoring should be done in patients on long-term agomelatine therapy. PMID- 26813707 TI - Surface hydrophobicity of slippery zones in the pitchers of two Nepenthes species and a hybrid. AB - To investigate the hydrophobicity of slippery zones, static contact angle measurement and microstructure observation of slippery surfaces from two Nepenthes species and a hybrid were conducted. Marginally different static contact angles were observed, as the smallest (133.83 degrees ) and greatest (143.63 degrees ) values were recorded for the N. alata and N. miranda respectively, and the median value (140.40 degrees ) was presented for the N. khasiana. The slippery zones under investigation exhibited rather similar surface morphologies, but different structural dimensions. These findings probably suggest that the geometrical dimensions of surface architecture exert primary effects on differences in the hydrophobicity of the slippery zone. Based on the Wenzel and Cassie-Baxter equations, models were proposed to analyze the manner in which geometrical dimensions affect the hydrophobicity of the slippery surfaces. The results of our analysis demonstrated that the different structural dimensions of lunate cells and wax platelets make the slippery zones present different real area of the rough surface and thereby generate somewhat distinguishable hydrophobicity. The results support a supplementary interpretation of surface hydrophobicity in plant leaves, and provide a theoretical foundation for developing bioinspired materials with hydrophobic properties and self-cleaning abilities. PMID- 26813708 TI - Metronidazole pharmacokinetics during rapid growth in turkeys - relation to changes in haemodynamics and drug metabolism. AB - Whereas interspecies variation in pharmacokinetics is a commonly investigated issue, variations in drug kinetics within a species are less documented. The aim of the study was to assess the influence of age-related changes in haemodynamics on the pharmacokinetics of metronidazole (MTZ) and its hydroxy metabolite (MTZ OH) in turkeys. MTZ was administered intravenously and orally at a dose of 25 mg/kg. Plasma drug and metabolite concentrations were assessed by high performance liquid chromatography, and pharmacokinetic parameters were calculated by noncompartmental analysis. Haemodynamic parameters (heart rate, stroke volume, cardiac output) were assessed by echocardiography and extraction ratio for MTZ was calculated based on total body clearance (ClB ). Between the 5th and 15th week of age, ClB of MTZ decreased from 3.6 to 1.2 mL/min/kg causing a twofold increase in the mean residence time (MRT) and elimination half-life (T1/2el ). The MTZ-OH production decreased threefold and its MRT and T1/2el increased. Although heart rate significantly decreased with age, cardiac output increased. Extraction ratio was low in all age groups. It is concluded that significant age dependent decrease in ClB of MTZ in turkeys resulted from decreased perfusion of the clearing organs and their reduced metabolic capacity. This phenomenon is probably species specific and may apply to other therapeutic agents. PMID- 26813709 TI - Personality over ontogeny in zebra finches: long-term repeatable traits but unstable behavioural syndromes. AB - A crucial assumption of animal personality research is that behaviour is consistent over time, showing a high repeatability within individuals. This assumption is often made, sometimes tested using short time intervals between behavioural tests, but rarely thoroughly investigated across long time intervals crossing different stages of ontogeny. We performed such a longitudinal test across three life stages in zebra finches (Taeniopygia guttata), representing about 15-20% of their life span in captivity, and found repeatabilities ranging from 0.03 to 0.67. Fearlessness and exploration were the most repeatable traits both within and across life stages. Activity and aggression were repeatable across, but not or only partly within life stages. Boldness was not repeatable. Furthermore, we found no evidence for a consistent behavioural syndrome structure across ontogeny. Our results indicate that the consistency of behavioural traits and their correlations might be overestimated and suggest that life-long stability of animal personality should not simply be assumed. PMID- 26813710 TI - Graphene-ferroelectric metadevices for nonvolatile memory and reconfigurable logic-gate operations. AB - Memory metamaterials are artificial media that sustain transformed electromagnetic properties without persistent external stimuli. Previous memory metamaterials were realized with phase-change materials, such as vanadium dioxide or chalcogenide glasses, which exhibit memory behaviour with respect to electrically/optically induced thermal stimuli. However, they require a thermally isolated environment for longer retention or strong optical pump for phase change. Here we demonstrate electrically programmable nonvolatile memory metadevices realised by the hybridization of graphene, a ferroelectric and meta atoms/meta-molecules, and extend the concept further to establish reconfigurable logic-gate metadevices. For a memory metadevice having a single electrical input, amplitude, phase and even the polarization multi-states were clearly distinguishable with a retention time of over 10 years at room temperature. Furthermore, logic-gate functionalities were demonstrated with reconfigurable logic-gate metadevices having two electrical inputs, with each connected to separate ferroelectric layers that act as the multi-level controller for the doping level of the sandwiched graphene layer. PMID- 26813711 TI - Test-retest reliability and discriminant validity for the Brazilian version of "The Interstitial Cystitis Symptom Index and Problem Index" and "Pelvic Pain and Urgency/Frequency (PUF) Patient Symptom Scale" instruments. AB - BACKGROUND: The purpose is to evaluate the psychometric properties of reliability and discriminant validity of the Brazilian Portuguese versions of two instruments used in the diagnosis of interstitial cystitis (IC): "The Interstitial Cystitis Symptom Index and Problem Index" (The O'Leary-Sant), and "Pelvic Pain and Urgency/Frequency (PUF) Patient Symptom Scale". METHODS: Three groups of patients were examined: a study group (subjects with IC), control group 1 (individuals with at least one IC symptom), and control group 2 (subjects without IC symptoms). Test-retest stability was evaluated at intervals of 3 to 7 days in the study group. Discriminant validity was examined in all three groups. RESULTS: The intraclass correlation coefficient (ICC) [95% confidence interval (CI)] results were 0.56 (range, 0.21-0.78) for The O'Leary-Sant Symptom Index, 0.48 (range, 0.10-0.73) for The O'Leary-Sant Problem Index, and 0.49 (range, 0.12-0.74) for the PUF. To analyze discriminant validity between groups, we used Fisher's exact test and odd ratio (OR) to identify differences. We obtained a P value<0.0001, which indicated that the null hypothesis was rejected; in other words, there was evidence that at least two different groups were compared to the proportion of patients with IC. CONCLUSIONS: The analyzed instruments did not reach appropriate values for reliability. Future studies are needed to analyze the psychometric measures of these instruments on a larger sample of patients with IC. PMID- 26813712 TI - The Hydrophobic Effect in Solute Partitioning and Interfacial Tension. AB - Studies of the partitioning of hydrophobic solutes between water and nonpolar solvents provide estimates for the energy cost of creating hydrophobic-water contacts. This energy is a factor of three lower than the work of adhesion derived from interfacial tension measurements. This discrepancy noted by Tanford in 1979 is widely viewed as a serious challenge to our understanding of hydrophobic interactions. However, the interfacial energy of a water-alkane interface depends on chain length. A simple analysis of published data shows that the loss of rotational freedom of an alkane chain at an interface accounts quantitatively for the length-dependent contribution to interfacial tension, leaving a length-independent contribution very close to the free energy of transfer per unit of solvent accessible surface area. This analysis thus clarifies the discrepancy between the thermodynamic and interfacial tension measurements of hydrophobic interaction energy. Alkanes do not loose rotational freedom when transferred between two different liquid phases but they do at an interface. This reconciles the difference between microscopic and macroscopic measurements. Like the partitioning free energy, the work of adhesion also has a large entropy and small enthalpy at 20 (o)C. PMID- 26813713 TI - [Child neglect situation and intervention outlook in rural areas of China]. AB - The neglect situation of rural children in China is serious, which is more serious than the same age group of urban children, especially the behind children are more severe. Child neglect deeply affects children's physical and mental health of children and adolescents in rural areas (from physical neglect, emotional neglect, education neglect, safety neglect, medical neglect and social neglect six aspects). To effectively prevent and control rural child neglect and promote the development of the physical and mental health of rural children and adolescents in China, we must adopt comprehensive measures including social, family and children three aspects. We need to cause the attention of the government and the society, improve the prevention of child neglect of social support networks, promote the social multi departments cooperation and efforts, and from the different angles to take effective intervention measure. To strengthen family intervention for the neglected children, to provide support and help to parents and families, as much as possible to eliminate or reduce the influence factors of child neglect. Should be aimed at high-risk group of child neglect, to adopt the principle of "early detection, early intervention", through to help and support to prevent or reduce the occurrence of neglect. PMID- 26813714 TI - [Pay attention to the human health risk of drinking low mineral water]. AB - The consumption of low mineral drinking water has been increasing around the world with the shortage of water resources and the development of advanced water treatment technologies. Evidences from systematic document reviews, ecological epidemiological observations, and experimental drinking water intervention studies indicate that lack of minerals in drinking water may cause direct or indirect harm to human health, among which, the associations of magnesium in water with cardiovascular disease, as well as calcium in water with osteoporosis, are well proved by sufficient evidence. This article points out that it is urgent to pay more attention to the issues about establishment of health risk evaluation system on susceptible consuming population, establishment of lab evaluation system on water quality and health effect for non-traditional drinking water, and program of safety mineralization for demineralized or desalinated water and so on. PMID- 26813715 TI - [Manganese neurotoxic effect and its susceptibility biomarkers of choice]. AB - Long-term occupational exposure to manganese might cause manganese poisoning, which would had adverse effects on nervous system of workers. The basal nucleus was damaged and dopaminergic neuron was injuried by manganese. The mechanism could be related with interfering the energy metabolism of central nerve, changing neurotransmitters, activating oxidation system and so on. Genetic factors may also plays a significant role in the neurotoxicity caused by manganese. Study the effects of manganese exposure biomarker, the neurotoxicity of biomarkers and the genetic susceptibility to early and susceptibility biomarkers will contribute to the prevention and control of manganese neurotoxicity. PMID- 26813716 TI - [Status analysis on child neglect of rural pupils aged 6-11 year-old in China]. AB - OBJECTIVE: To analyze pupils' neglect status aged 6-11 years in China's rural. METHODS: According to the principle of multi-stage stratified cluster sampling, to extract 7,943 pupils aged 6-11 years for the survey from 56 primary schools in 28 counties in nine provinces, from December 2012 to March 2013. Proceed questionnaire survey by the scale from "Neglect Evaluation Norms for pupils aged 6-8 years in Rural Areas of China" and "Neglect Evaluation Norms for pupils aged 9-11 years in Rural Areas of China". And analyze neglect rates and neglect degrees of the different grades, gender, family types and different levels of neglect. RESULTS: The total neglect rate of China's rural pupils aged 6-8 and 9 11 years was 40.2% (1,258/3,130) and 42.5% (1,498/3,526) respectively, which differences had no statistical significant (chi2=3.59, P=0.058); the total neglect degree was 46.04+/-8.87 and 44.78+/-10.43 respectively, which differences had statistical significant (t=5.01, P<0.001); the differences of neglect rates and neglect degrees between male (41.4% (657/1,587) and 46.28+/-8.76) and female (39.0% (601/1,543) and 45.78+/-8.97) of aged 6-8 were all no statistical significant (chi2=1.87, P=0.171; t=1.49, P=0.136); the neglect rates and neglect degrees of male (46.3% (816/1,763) and 45.53+/-10.11) were higher than female (38.7% (682/1,763) and 44.06+/-10.69) in the group of aged 9-11, which differences were all statistical significant (chi2=20.84, t=3.97, P<0.001); the male neglect rate in the group of aged 6-8 in social neglect (11.7% (198/1,691)) and the neglect degree in educational neglect (48.09+/-9.70) were higher than female (9.4% (155/1,648) and 47.37+/-9.89), which differences were all statistical significance (chi2=14.55, P<0.001, t=2.22, P=0.026), the male neglect rate in the group of aged 9-11 in physical neglect (20.4% (398/1,954)) was higher than female (16.7% (326/1 957)), which differences had statistical significance (chi2=8.92, P=0.003). CONCLUSION: The neglect status of Chinese pupils aged 6-11 years in rural was serious, and we should find out risk factors and provide efficient prevention measures. PMID- 26813717 TI - [Impact factors analysis on child neglect of children aged 3-6 year-old in rural areas of China]. AB - OBJECTIVE: To investigate the major influence factors of child neglect among rural areas children aged 3-6 years in China. METHODS: According to multi-stage stratified cluster sampling, distribution characteristics and the level of economic development, we randomly sampled 10 provinces, 26 cities (8 capital cities, 16 prefecture-level cities and 2 municipalities) using lottery method. Depending on the different level of economic and cultural, we sampled one medium county from each city (municipalities sampled two counties), a total of 28 counties. All towns were divided into high, medium and low three levels in accordance with economic and cultural, each level sampled one town, each conty sampled three towns, a total of 84 towns were sampled. Each town sampled 40 children, including 20 boys and 20 girls (including each 10 children aged 3 to 6, half and half boys and girls). 4 096 rural children aged 3-6 years old were sampled and surveyed of China. Based on "the Neglect Norms for Children Aged 3 to 6 Years Old in Rural Areas of China" explored the risk factors of child neglect. SPSS 18. 0 for windows was employed for statistics analysis. Multifactorial analysis was conducted through multivariate Logistic Regression. RESULTS: The total neglected rate of the rural children aged 3 to 6 was 53.7% (2,047/3,810), and the total neglected degree was 44.42+/-7.57. The multivariate logistic regression analysis showed that, neglected risk of the boys was higher than the girls (OR=1.30, 95% CI: 1.13-1.49), neglected risk of children were higher, when their mothers were migrant workers (OR=2.18, 95% CI: 1.59-3.00); the lower educational level of mothers, the higher neglected risk of children, the children in families that mothers only received primary education or was uneducated were most likely to be neglected (OR=2.92, 95% CI: 1.91-4.47), the second was the families that mothers received primary education (OR=1.86, 95% CI: 1.29-2.69); the lower the household income, the easier to be neglected the children, the easiest one was the household income less than 5000 RMB (OR=2.85, 95% CI: 2.14 3.79), the second was 5000-9,999 RMB (OR=1.76, 95% CI: 1.40-2.20); the relationship between children and mothers was distanced, neglect risk of children was higher (OR=3.88, 95% CI: 1.31-11.52); left behind children were easier to be neglected (OR=1.30, 95% CI: 1.09-1.54). CONCLUSION: The influence factors among children aged 3-6 years in the rural areas of China were boys, mother's occupation, maternal education level, the relationship between children and mothers, household income and left-behind children. PMID- 26813718 TI - [Research on child neglect situation and influential factors of left-behind children and living-with-parents children aged 6-17 year-old in rural areas of two provinces, western China]. AB - OBJECTIVE: To investigate the situation and the influential factors of child neglect between left-behind children and living-with-parents children aged 6-17 years in the rural areas in western China. METHODS: Students were randomly selected according to the principle of multi-stage stratified cluster sampling and they were from three cities in Shanxi and four districts in Chongqing. Among the 4,131 children, there were 1,874 students in the 6-11 years group and the left-behind children accounted for 50.21% (941/1,874) in this group. There were 2,257 students in the 12-17 years old group and the left-behind children accounted for 53.35% (1,204/2,257) in this group. The questionnaire named "Evaluation on Neglect for Elementary and Secondary School Students Aged 6-17 Years in Rural Areas in China" was used in the field investigation. The students' neglect frequency was described by neglect rate and the factors affecting students' neglect were analyzed by means of binary logistic regression. RESULTS: In the 6-11 years old group, the neglect rates of left-behind children and living with-parents children were 63.03% (474/752) and 43.87% (347/791), respectively (chi2=58.86, P<0.001). In the 12-17 years old group, the neglect rates of left behind children and living-with-parents children were 60.64% (627/1 034) and 53.57% (495/924), respectively (chi2=9.96, P<0.001). For factors influencing left behind children, compared to the factors about boys, younger mother (<=40 years old), presence of parents' income reduction within the last year and nuclear family, the factors about girls, elder mother (41-49 years), absence of parents' income reduction within the last year and three-generation family or single parent family were associated with lower neglect risk, and OR values were 0.67, 0.68, 0.70, 0.73, and 0.43 (P<0.05); compared to the factors about Han nationality, only child, with separate room at home, and resident children, the factors about other nationalities, non-only child, no separate room at home, and non-resident children were associated with high neglect risk, and OR values were 1.85, 1.34, 1.46, and 1.32 (P<0.05); compared to the lower father's education background (primary school or uneducated), the higher father's education background (junior middle school, senior middle school, technical secondary school, college and above) was associated with lower neglect risk, and OR values were 0.66, 0.50, and 0.25 (P<0.05); compared to good relationship between children and parents as well as good relationship between parents, fair or poor relationship was associated with high neglect risk, and OR values were 1.57-3.79 (P<0.05). For factors influencing non-left-behind children, compared to the factors about younger mother (<=40 years old), changes of patient's work in the last year, presence of parents' income reduction within the last year and nuclear family, the factors about elder mother (41-49 years), no changes of patients' work in the last year, absence of parents' income reduction within the last year and three-generation family or single-parent family were associated with lower neglect risk, and OR values were 0.69, 0.71, 0.75, 0.82, and 0.56 (P<0.05); compared to the factors about Han nationality, only child and younger father (<=40 years old), other nationalities, the factors about non-only child, and elder father (41-49 years) were associated with high neglect risk, and OR values were 1.45, 1.56, and 1.57 (P<0.05); compared to lower father's education background (primary school or uneducated), higher father's education background (junior middle school, senior middle school, technical secondary school, college and above) was associated with lower neglect risk, and OR values were 0.65 and 0.49 (P<0.05); compared to good relationship between children and parents as well as good relationship between parents, fair or poor relationship was associated with high neglect risk, and OR values were 1.56-7.69 (P<0.05). CONCLUSION: The situation of child neglect among left-behind children aged 6-17 years in rural areas of the two provinces in western China was serious, their neglect rates were higher than those of living-with-parents children, and there were many risk factors affecting the neglect rates of the two group children. PMID- 26813719 TI - [Analysis of effect of screening of esophageal cancer in 12 cities and counties of Henan province]. AB - OBJECTIVE: To evaluate effect of screening of esophageal cancer at rural areas in Henan province. METHODS: At rural areas with high incidence of upper gastrointestinal carcinoma in Henan province total of 88,263 persons with 40 to 69 years old were set to the target population of the screening by the 12 cities and countries and endoscope and pathology diagnosis were performed during 2009 2013. For patients with precancerous lesions, follow-up visits were conducted and defined as follows: once in three years for patients with mild dysplasia, once per year for moderate hyperplasia patients, the patients with severe intraepithelial neoplasia/carcinoma in situ should be treat, at least once per year for those one who didn't under treatment. The result data of screening were summarized and detection rates of esophagus hyperplasia, carcinoma in situ, early and middle-late cancer were calculated, as well as the early diagnosis rate. The result between first round and follow-up screening was compared. RESULTS: Target population were examined in first round screening. There were 8,434 persons with above mild dysplasia and the detection rate was 9.56%, among them there were 7,224 (8.18%) cases with light-middle hyperplasia, 789 (0.89%) cases with serious dysplasia or cancer in situ, 239 (0.27%) cases with early cancer and 182 (0.21%) cases with middle-late cancer. The sum of serious dysplasia or cancer in situ and early cancer was 1 028 and the early detection rate was 84.96% (1,028/1,210). From 2012 to 2013, the follow-up screening for persons with light-middle hyperplasia which should be followed 4,230 cases, there were 2 853 people to take in screening and compliance was 67.45%. Total of 94 cases were diagnosed with cancer in situ or early cancer. The detection rate and the early detection rate were 3.29% and 100%, respectively. The rates of detection and early detection in phase of follow-up screening were statistically significantly higher than that in first round screening respectively (P<0.001). CONCLUSION: At rural areas of high incidence upper gastrointestinal carcinoma in Henan province, the screening with endoscope had good effect and strengthening the follow-up screening could increase the effect. PMID- 26813720 TI - [The prediction of high-sensitivity C reactive protein for peripheral arterial sclerosis in middle-aged population]. AB - OBJECTIVE: To explore the predictive value of high-sensitivity C reactive protein (hsCRP) in middle-aged population during the peripheral arteriosclerosis. METHODS: Random sampling method was used in the study. In 2006-2007 Kailuan Group health examination of 101,510 employees, using stratified random sampling method to select 5,852 as observational cohort included, in the final with a standard queue 5,440 in December 2009. This study selected to participate in the 2012-2013 health examination cohort as the research object, in accordance with the inclusion criteria ultimately selected survey 3,978, select the epidemiological investigation, physical examination, laboratory testing data analysis. Of the 3 978 subjects, 2,282 were male and 1,696 were female, and the baseline age was (53.80+/-11.14) years. According to the baseline hsCRP quartile level was divided into four groups for comparison of baseline data, using multiple linear regression analysis between hsCRP and brachial-ankle pulse wave velocity (baPWV). Area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the prediction of hsCRP levels in peripheral arteriosclerosis. RESULTS: With increase of hsCRP levels, the survey of baseline levels of baPWV showed increasing trend, (1,445.49+/-300.55), (1,494.46+/-307.94), (1,547.67+/-320.34), (1,621.32+/-342.53) cm/s, respectively. Multiple linear regression results showed that age, by logarithmic transformation of hsCRP (lghsCRP) level, systolic blood pressure and fasting blood glucose for each additional unit, baPWV levels were increased 266.47, 58.00, 5.02, 39.79 cm/s (P<0.001), and BMI for each additional unit, baPWV level decreased 9.52 cm/s (P=0.030). The prediction of hsCRP in peripheral artery showed that lghsCRP level of AUC to 0.59 (95% CI: 0.57-0.61), lower than the age and systolic blood pressure predicted value AUC (95% CI) of 0.69 (0.67-0.71), 0.75 (0.73-0.77), respectively. CONCLUSION: The hsCRP level could not predict the peripheral arteriosclerosis alone, and the combined age and systolic blood pressure level could have better predictive value. PMID- 26813721 TI - [Western area surge for controlling Ebola hemorrhagic fever outbreak in Sierra Leone and evaluation of its effect]. AB - OBJECTIVE: To investigate the Western Area Surge (WAS) program in the Ebola outbreak of Sierra Leone, and to analyze its implementing effect. METHODS: The subject of this study was 3,813 laboratory confirmed Ebola hemorrhagic fever (EHF) cases reported in Sierra Leone from November 19, 2014 through January 27, 2015, a period before and after the implementation of the WAS program. To analyze and make conclusions according to the working experience of China Mobile Laboratory Reponses Team in the fight of Ebola outbreak, using WHO published EHF case definition to make diagnosis and compare the number of bed numbers, confirmed EHF cases, samples tested, and positive rates before and after implementation of WAS program. RESULTS: From the implementation of WAS program on 17th December 2014 to half a month later, the total numbers of Ebola holding and treatment centers increased from 640 to 960, six additional laboratories were established. On January, 2015, another two laboratories from America and The Netherlands were established. The numbers of samples tested one month before and after WAS program were 7,891 and 9,783, respectively, with an increase of 24.0 percent, while the positive rate of Ebola virus decreased from 22.2% (1,752/7,891) to 11.0% (1,077/9,783). The positive rate of blood samples decreased from 39.6% (248/626) in the month before WAS program to 27.4% (131/478) (chi2=17.93, P<0.001) in the mother after WAS program, the positive rate of blood samples 22.7% (103/454) to 10% (62/609) (chi2=31.03, P<0.001), accordingly. After 3 weeks of WAS program, in addition to Western Area, another four hotspots in Sierra Leone had also reported a significant decrease of the numbers of confirmed EVD cases. Forty-two days after implementation of WAS program, the daily number of laboratory confirmed EHF cases decreased from 63 to 10. CONCLUSION: WAS program played a vital role in controlling the EHF outbreak rapidly in Sierra Leone. It could also provide guidance for the control similar large infectious diseases outbreak in the future. PMID- 26813722 TI - [Discovery and whole genome sequences analysis of a dengue virus type 1 strain isolated in Henan province]. AB - OBJECTIVE: To diagnose imported dengue fever case from Henan province, and to sequence and analyze the characteristics of whole genome sequence, and to explore the possible viral origin source. METHODS: A suspected dengue fever case was reported in Yuzhou city, Henan province. The patient returned from foshan, Guangdong province on September 19, 2014, after the epidemiological investigation and serum specimen collected, which dengue fever case was diagnosed in the laboratory, then it was inoculated on Vero cells. Whole genome sequence was amplified by several pairs primers and characterized using biologic software. RESULTS: The imported case was diagnosed as dengue virus 1 serotype infection. Dengue 1 strain was isolated using Vero cells successfully. Whole genome was 10,670 nt, which belonged to dengue virus 1 serotype V genotype and didn't found any recombination event. The phylogenetic analysis demonstrated that the strain was closed to Indian starins isolated in 2008-2011, and the homology of nucleotide sequence was between 98.2%-99.4%. CONCLUSION: It was the first time to discover imported dengue 1 serotype case in Henan province. However, according to the patient has been to Guangdong province before onset, it inferred that the Indian strain had been imported to Guangdong province before this case in Henan province. PMID- 26813723 TI - [Risk assessments and control strategies of plague in five key surveillance counties, Zhejiang province]. AB - OBJECTIVE: To analyze the epidemiology data on plague in five counties in Zhejiang province and to evaluate the risk of plague in theses areas. METHODS: We selected five monitoring stations as a risk assessment (Qingyuan county, Longquan city, Yiwu city, Wencheng county, and Ruian city) in Zhejiang province where the plague epidemic more serious in the history. At least one constant site and 1-4 variable sites where plague occurred in history were selected for monitoring. We collected the five counties (cities) surveillance data of indoor rat density, indoor Rattus flavipectus density, the Xenopsylla cheopis index of rat, the Xenopsylla cheopis index of Rattus flavipectus in 1995-2014. Isolation of Yersinia pestis was conducted among 171,201 liver samples and F1 antibody were detected among 228,775 serum samples. Risk matrix, Borda count method, and Delphi approach were conducted to assess risk of the plague of five counties (cities) in Zhejiang province. RESULTS: Indoor rat density in Qingyuan county, Longquan city, Yiwu city, Wencheng county, Ruian city was 1.58%-5.50%, 1.13%-9.76%, 0.56%-3.67%, 2.83%-16.08%, 7.16%-15.96%, respectively; Indoor Rattus flavipectus density of five counties (cities) was 0.08%-2.23%, 0-2.02%, 0-0.54%, 0.71%-5.58%, 0.55% 4.92%, respectively. The Xenopsylla cheopis index of rat in Qingyuan county and Wencheng county was 0.011-0.500 and 0.015-0.227, respectively; The Xenopsylla cheopis index of Rattus flavipectus of Qingyuan county and Wencheng county was 0.119-3.412 and 0.100-1.430, respectively; Ruian City and Yiwu city cannot collected Xenopsylla cheopis, Long quan city only collected the Xenopsylla cheopis index of rat in the five years. Yersinia pestis were not isolated in five counties (cities).There were 3 Apodemus agrarius samples positive of plague F1 antibody test, in Longquan city and Yiwu city in 2005. Borda count method to assess the Longquan city, Yiwu (Borda point were both 321) plague risk was higher than three other regions; Delphi approach to evaluation five counties (cities) belong to the plague had a lower risk areas, according to the level of risk score (Pf) Longquan city and Yiwu (Pf was 0.314, 0.292, respectively) plague risk were higher than three other regions (Pf were all 0.292). CONCLUSION: The main host and media were lower in five key plague surveillance counties (cities) of Zhejiang province; The result of Borda count method and Delphi approach for risk assessment indicated that endogenous plague recrudescence was at lower level, but Longquan city and Yiwu city risk were higher than other counties (cities). PMID- 26813724 TI - [Drug-resistance characteristics of CRF01_AE and CRF07_BC subtypes of HIV-1 strains in Sichuan province]. AB - OBJECTIVE: To investigate the drug resistance of HIV patients to the HIV-1 CRF01_AE and CRF07_BC strains in Sichuan province during 2010 to 2013. METHODS: 1.5 ml of plasma were collected from AIDS patients who had been receiving anti retroviral treatment for over 6 months but still had a HIV-1 virus load of over 1 000 copies/ml from January 1, 2010 to December 31, 2013 in Sichuan province. Genetic analysis of the HIV-1 pol gene was performed using self-established method, and patients with a positive drug-resistant HIV-1 pol gene mutation were included. HIV-1 poly gene was successfully sequenced for a total of 1 213 patients. Drug resistance of different HIV-1 strains was compared with chi2 test or Fisher exact test. RESULTS: 558 cases (46.0%) of the 1 213 successfully sequenced patients were infected by HIV-1-strains with drug-resistant mutations, including 327 cases (58.6%) infected by CRF01_AE strain, 126 (22.6%) by CRF07_BC strain, 46 (8.2%) by CRF08_BC strain, 33 (5.9%) by B strain, 4 (0.7%) by C strain, 1 (0.2%) by CRF02_AG strain, and 21 (3.8%) by unidentified strains. Drug resistant mutation analysis revealed that L33, F116, L74, Q151, and T69 resistance mutations occurred only in the CRF01_AE strain, while A71, K43, and Q58 resistance mutations occurred only in the CRF07_BC strain; in nuclear nucleoside reverse transcriptase inhibitors (NRTIs) and non nucleoside reverse transcriptase inhibitors (NNRTIs), CRF01_AE subtype strains showed highly resistant rate were higher than CRF07_BC, CRF08_BC and B subtype strains, with the differences were statistically significant (P<0.05). CONCLUSION: The drug resistant HIV-1 strains in Sichuan mainly included the CRF01_AE and CRF07_BC strains, which had different resistance mutations. PMID- 26813725 TI - [Influential factors analysis on the survival time of patients infected with tuberculosis and HIV]. AB - OBJECTIVE: To investigate the predictors that reduced the survival time on HIV positive TB patients during their first year's anti-TB therapy. METHODS: A retrospective study was conducted to review 519 TB/HIV co-infection patients from an Internet based TB surveillance system. We collected information of demography, HIV status, CD4+ lymphocytes count, antiretroviral therapy (ART), sputum smear results of diagnosis and around 2 months' initiation of anti-TB therapy, et al. Wilconxon rank sum test was used to compare the difference of age and CD4+ lymphocytes, count and Cox Uni-variable, and Multi-variable analysis were used to compare the different distribution of rest of risk elements between the groups of death and survival; survival function also has been used to evaluate the top 4 risk elements that have made negative impact on the survival time of HIV positive TB patients during their first year's anti-TB therapy. RESULTS: Among 519 TB/HIV patients, 84 (16.18%) were dead, 435 (83.82%) survived. Median age (P50 (P25 P75)) in survival was 51.0 (41.0-65.0), while in death was 45.0 (35.0-60.0) (U= 2.68, P=0.007). There was significant difference between survival and death. Median CD4+ lymphocyte count in survival and death (P50 (P25-P75)) were 69.00 (26.00-131.20) and 114.50 (35.00-245.00), respectively, significant difference also has been observed. Based on the Cox analysis, patients with less than 2 months' intensive anti-TB therapy, poor treatment adherence, less than 4 months continue anti-TB therapy and sputum smear positive around 2 months initiation of anti-TB therapy had higher risk of death, the Relative Risk value (RR) were 1 100.40 (95% CI: 105.62-11,470.00), 52.91 (95% CI: 27.42-102.13), 49.43 (95% CI: 6.38-382.81), and 15.83 (95% CI: 2.55-98.40), respectively. Log-rank test results showed that there were significant difference between survival and death groups with anti-TB intensive therapy duration (Log-Rank value was 236.0, P<0.001), adherence (Log-Rank value was 302.9, P<0.001), and sputum smear results around 2 months' anti-TB initiation (Log-Rank value was 7.55, P=0.006). CONCLUSION: Known HIV positive, less CD4+ lymphocyte count, not initiation of ART, sputum smear positive, around 2 months' initiation of anti-TB therapy, not enough anti-TB therapy duration of intensive and continue period and poor treatment adherence were the predictors of death of HIV positive TB patients in the first year's anti TB therapy. PMID- 26813726 TI - [Expression of heat shock protein 70 and its mRNA in career exposure to manganese]. AB - OBJECTIVE: To analyze the expression levels of heat shock protein70 (HSPs70) and HSPs70 mRNA in different exposure to manganese, and research the neuroprotective effect on the career exposure to manganese. METHODS: From 2008 to 2009, with cross-sectional study design, and in a locomotive and rolling stock works, by stratified random sampling method, the exposed sample consisted of 180 welders from different welding shops and 100 unexposed in the last three years, non welder controls with age-matched workers of similar socioeconomic status from the same industry. The control workers had not been exposed to neurotoxic chemicals. The mRNA expressions of four different metabolic enzyme were detected by SYBR Green I quantitative real-time polymerase chain reaction. The expression levels of the two enzymes mRNA in different exposure to manganese were analyzed. The expressions of HSPs70 were detected by Western blot. The concentration of air manganese was determined by GFAAS. The average concentration of 8 h time (8h-TWA) was used to express the level of individual exposure to manganese, according to the air manganese workplace occupational exposure limit (8h-TWA=0.15 mg/m3), the exposed group is divided into high exposed group (>0.15 mg/m3) and low exposure group (<0.15 mg/m3). RESULTS: The individuals exposed to manganese dose of exposed group ((0.25+/-0.31) mg/m3) was higher than the control group ((0.06+/ 0.02) mg/m3) (t=6.15, P=0.001); individuals exposed to manganese dose of high exposure group for (0.42+/-0.34) mg/m3, which was higher than low exposure group (0.09+/-0.07) mg/m3 (t=9.80, P=0.001). HSPs70 mRNA and protein of exposure group (5.65+/-0.21, 3.26+/-0.15) were higher than the reference group (0.41+/-0.03, 1.32+/-0.12) (t=18.91, t=8.68, P=0.001). HSP70 mRNA and protein of high exposure group (6.48+/-0.37, 3.67+/-0.26) were higher than the low exposure group (5.15+/ 0.23, 3.02+/-0.19) (t=3.24, t=2.01, P=0.003, P=0.043). CONCLUSION: The expression of peripheral blood lymphocytes HSPs70 level and HSPs70 mRNA workers exposed to manganese increased and protect nerve cells from related to Mn stimulation induced lipid peroxidation damag. PMID- 26813727 TI - [Distribution of copper and zinc level in urine of general population in eight provinces of China]. AB - OBJECTIVE: To describe the distribution of zinc (Zn) and copper (Cu) in urine samples of generalpopulation in eight provinces of China, to analyze their characteristics of distribution between different region, gender and age-cohorts, and to provide the baseline of themetabolites in the general population. METHODS: From 2009 to 2010, 18 120 subjects from the general population aged from 6 to 60 years old were recruited from 24 areas among 8 provinces of China mainland by random sampling. The environmental and physical condition characteristics were collected from questionnaires, and urine samples were collected at the mean time. The levels of Zn and Cu in urine were measured using ICP-MS. Data were analyzed by statistical methods to compare the distribution characteristics of Zn and Cu among populations with different ages and genders. RESULTS: Totally, the median of Cu and Zn in urine were 9.28 and 115.47 ug/L respectively; and the inter quartile range of Cu and Zn were 2.66-16.09 and 35.32-265.15 ug/L respectively. The median of Cu in male and female were 9.90 and 8.60 ug/L (Z=-5.63, P<0.001), and Zn in male and female were 140.44 and 95.27 ug/L (Z=-14.79, P<0.001). The median of Cu among the groups aged 6-12, 13-16, 17-20, 21-30, 31-45 and 46-60 years old were 9.30, 10.14, 9.67, 9.33, 8.38 and 8.74 ug/L (chi2=70.94, P<0.001), respectively, and the median of Zn 130.83, 132.07, 139.34, 109.3, 78.74 and 109.51 ug/L ((chi2=146.00, P<0.001), respectively.There was statistically significant differences in urinary Cu and Zn levels between male and female, and among the different age groups. CONCLUSION: The Cu and Zn levels and distribution in urine among general population between 2009 and 2010 in China were reported in this article. These basic data in China will provide scientific and reliable reference for further scientific research. PMID- 26813728 TI - [The effect of occupational stress on depression symptoms among 244 policemen in a city]. AB - OBJECTIVE: To explore the influence of occupational stress related factors on depression symptoms among 244 policemen in a city in China. METHODS: In May 2011, 287 policemen from a city public security bureau were recruited to this survey by cluster sampling method. We deleted questionnaires which include missing variables on demographic characteristics and factors associated with occupational stress questionnaires which include over 3 missing items. 244 policemen were included in this study. Depression symptoms and occupational stressors were measured using Chinese version of depression self-reported questionnaire, job content questionnaire, Chinese version of effort-reward imbalances questionnaire, job hazard scale and occupational stress inventory. Depression symptom scores and the relationship between the variables and occupational stress were analyzed by Spearman correlation analysis and multiple regression analysis. RESULTS: The Median (P25-P75) of depression symptom scores of all respondents was 16.50 (11.00 25.00). 144 were policemen with no depression symptoms and 100 were with depression symptoms. The median (P25-P75) of depression symptoms scores among policemen with length of serves <10, 10-19, 20-29 and >=30 was 17.00 (8.00 26.00), 16.00 (11.00-24.50), 19.00 (12.00-27.00), and 12.00 (6.25-15.00), respectively. The difference of scores was significant among length of serves groups (chi2=9.52, P=0.023). The scores of psychological demands, sleep disorder, daily life stress and negative affectivity among policemen with depression symptoms were 17.00 (8.00-26.00), 16.00 (11.00-24.50), 19.00 (12.00-27.00), and 12.00 (6.25-15.00), respectively, which were higher than those with no depression symptoms (24.00 (22.00-25.00), 8.00 (5.00-13.00), 8.00 (6.00-10.00), 1.00 (0 2.75)), and the differences were significant (Z=3.82, 5.39, 5.15, 6.41, P<0.001). Spearman correlation analysis revealed that depression symptoms score was positively related to sleep disorder, commitment effort, psychological demands, daily life stress, negative affectivity and job hazards scores. Correlations coefficient were 0.44, 0.28, 0.28, 0.33, 0.38, 0.44, and 0.38, respectively (P<0.001). Multiple linear regression analysis indicated that self-esteem, daily life stress and negative affectivity had bigger contribution on the depression symptoms scores. The standard regression coefficient was -0.46, 0.19 and 0.13, respectively (P<0.001, P=0.001, P=0.030). CONCLUSION: Sleep disorder, commitment effort, psychological demands, daily life stress, negative affectivity and job hazards scores were the inducement of depression symptoms for policemen. To reduce the daily life stress, negative affectivity and improve the quality of sleep, add to self-esteem, reward and social support have positive effects on reducing the occurrence of depressive symptoms for police. PMID- 26813729 TI - [A survey on the mineral contents and potential renal acid loads in primary and secondary school-supplied drinking water in Chongqing]. PMID- 26813730 TI - [Immunogenicity of primary doses of serogroup A, C meningococcal conjugate vaccine]. PMID- 26813731 TI - Perturbation of nucleo-cytoplasmic transport affects size of nucleus and nucleolus in human cells. AB - Size regulation of human cell nucleus and nucleolus are poorly understood subjects. 3D reconstruction of live image shows that the karyoplasmic ratio (KR) increases by 30-80% in transformed cell lines compared to their immortalized counterpart. The attenuation of nucleo-cytoplasmic transport causes the KR value to increase by 30-50% in immortalized cell lines. Nucleolus volumes are significantly increased in transformed cell lines and the attenuation of nucleo cytoplasmic transport causes a significant increase in the nucleolus volume of immortalized cell lines. A cytosol and nuclear fraction swapping experiment emphasizes the potential role of unknown cytosolic factors in nuclear and nucleolar size regulation. PMID- 26813732 TI - Angiographic predictors of 2-year stent thrombosis in patients receiving drug eluting stents: Insights from the ADAPT-DES study. AB - OBJECTIVES: We sought to identify angiographic predictors of 2-year stent thrombosis (ST) in the ADAPT-DES study. BACKGROUND: A strong relationship between platelet reactivity and ST after implantation of drug-eluting stents (DES) was recently confirmed in the prospective, multicenter ADAPT-DES study. METHODS: In a pre-specified analysis of patients enrolled in ADAPT-DES, an independent angiographic core laboratory performed detailed angiographic analyses for all cases of ST. Patients with Academic Research Consortium definite/probable target lesion ST were matched with controls in a 1:2 ratio, and multivariable Cox regression models identified angiographic predictors of 2-year ST. RESULTS: Among 8,582 patients who had successful percutaneous coronary intervention (PCI) and were included in the ADAPT-DES study, 92 (1.1%) patients had ST at 2-year follow up. Target lesion-related ST was identified in 77 patients (82 lesions) who were clinically matched with 153 patients (196 lesions) without ST. Patients with ST were more likely to have longer target lesions, thrombus, moderate/severe calcification, American College of Cardiology/American Heart Association (ACC/AHA) type C lesions, and saphenous vein grafts. After adjustment for clinical covariates the angiographic variables that predicted ST were lesion complexity (ACC/AHA type C lesion, adjusted HR: 1.97, 95% CI: 1.19 to 3.26, P = 0.01) and presence of thrombus on index PCI (HR: 2.25, 95% CI: 1.40 to 3.59, P < 0.01). CONCLUSIONS: Anatomically complex lesions and the presence of thrombus are strong predictors of 2-year ST in the DES era. (c) 2016 Wiley Periodicals, Inc. PMID- 26813733 TI - Affinity-Mediated Homogeneous Electrochemical Aptasensor on a Graphene Platform for Ultrasensitive Biomolecule Detection via Exonuclease-Assisted Target-Analog Recycling Amplification. AB - As is well-known, graphene shows a remarkable difference in affinity toward nonstructured single-stranded (ss) DNA and double-stranded (ds) DNA. This property makes it popular to prepare DNA-based optical sensors. In this work, taking this unique property of graphene in combination with the sensitive electrochemical transducer, we report a novel affinity-mediated homogeneous electrochemical aptasensor using graphene modified glassy carbon electrode (GCE) as the sensing platform. In this approach, the specific aptamer-target recognition is converted into an ultrasensitive electrochemical signal output with the aid of a novel T7 exonuclease (T7Exo)-assisted target-analog recycling amplification strategy, in which the ingeniously designed methylene blue (MB) labeled hairpin DNA reporters are digested in the presence of target and, then, converted to numerous MB-labeled long ssDNAs. The distinct difference in differential pulse voltammetry response between the designed hairpin reporters and the generated long ssDNAs on the graphene/GCE allows ultrasensitive detection of target biomolecules. Herein, the design and working principle of this homogeneous electrochemical aptasensor were elucidated, and the working conditions were optimized. The gel electrophoresis results further demonstrate that the designed T7Exo-assisted target-analog recycling amplification strategy can work well. This electrochemical aptasensor realizes the detection of biomolecule in a homogeneous solution without immobilization of any bioprobe on electrode surface. Moreover, this versatile homogeneous electrochemical sensing system was used for the determination of biomolecules in real serum samples with satisfying results. PMID- 26813734 TI - Small Cell Variant of T-Cell Prolymphocytic Leukemia with Acquired Palmoplantar Keratoderma and Cutaneous Infiltration. AB - T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive post-thymic malignancy that is characterized by the proliferation of small- to medium- sized prolymphocytes. The classic clinical features of T-PLL are lymphocytosis, lymphadenopathy, hepatosplenomegaly, and skin lesions. Skin involvement varies clinically from diffuse infiltrated erythema. Infiltration is localized to the face and ears, nodules, and erythroderma. We present a case of small cell variant of T-PLL in a patient who presented with unusual cutaneous manifestations of acquired palmoplantar keratoderma (PPK) followed by diffuse erythematous infiltrated papules and plaques involving the trunk. When the etiology of acquired PPK is not clear, the physician should consider the possibility of an underlying malignant disease. In this case, the diagnosis of T-PLL was subsequently confirmed by laboratory and cytological findings, as well as by the immunophenotyping of leukemic cells in skin biopsy. Since paraneoplastic acquired PPK may be the initial evident sign of malignancy, the physician's awareness of this manifestation may be crucial for early diagnosis and treatment. Our case emphasizes the importance of accurate evaluation of skin lesions and early skin biopsy in the diagnosis of some hematological malignancies. PMID- 26813735 TI - Prevention of bone metatasis in prostate cancer by denosumab: Unneeded endpoint or unmet need? PMID- 26813736 TI - Autonomy Support and Recovery Practice at a Psychosocial Clubhouse. AB - PURPOSE: To explore how recovery practices are embodied in the behavior of staff and implemented by staff and members at a psychosocial clubhouse. DESIGN AND METHODS: Case study design guided 120 hr of participation observation and 18 interviews at a psychosocial clubhouse. Data were subjected to thematic analysis guided by self-determination theory. FINDINGS: "Autonomy support" emerged as an overarching theme, with three subthemes: "voice cultivating," "talent scouting," and "confidence coaching." PRACTICE IMPLICATIONS: Autonomy support is an important means of supporting the self-determination of clubhouse members. The findings of this study inform the ongoing development of the clubhouse involved and also provide insights for health services generally in relation to how to implement recovery-oriented practice. PMID- 26813738 TI - Published and unpublished evidence in coverage decision-making for pharmaceuticals in Europe: existing approaches and way forward. AB - BACKGROUND: Dissemination bias occurs when only some results emerging from clinical research reach their intended audience in the knowledge translation process. Given that coverage decisions increasingly rely on evidence, it is important to explore the types of evidence considered. This paper aimed to examine the evidence base used by regulatory institutions involved in pricing and reimbursement of pharmaceuticals in a broad range of European countries, as well as their awareness of and approach towards dissemination bias. METHODS: A mixed methods approach was adopted. Regulatory documents and published literature were identified in systematic searches and relevant documents were analysed. An online survey was carried out to verify and expand insights. RESULTS: Forty-two relevant regulatory documents and 10 publications were included. The survey had a 35% response rate, yielding valid responses for 13 countries. A fragmented impression was obtained for most countries indicating a general lack of transparency regarding both processes of decision-making and approaches towards unpublished information. Dissemination bias was rarely consistently considered. Practices for the identification and inclusion of all available evidence varied considerably, as did the influence of missing evidence on decision-making. Differences were often attributable to the regulatory context and/or institutional principles. CONCLUSIONS: Best practice is difficult to generalize given the identified variations. Individual exemplary practices support the necessity for institutional exchange at international level. Increased institutional commitment to transparency of methods and processes should be advocated. PMID- 26813737 TI - MoodHacker Mobile Web App With Email for Adults to Self-Manage Mild-to-Moderate Depression: Randomized Controlled Trial. AB - BACKGROUND: Worldwide, depression is rated as the fourth leading cause of disease burden and is projected to be the second leading cause of disability by 2020. Annual depression-related costs in the United States are estimated at US $210.5 billion, with employers bearing over 50% of these costs in productivity loss, absenteeism, and disability. Because most adults with depression never receive treatment, there is a need to develop effective interventions that can be more widely disseminated through new channels, such as employee assistance programs (EAPs), and directly to individuals who will not seek face-to-face care. OBJECTIVE: This study evaluated a self-guided intervention, using the MoodHacker mobile Web app to activate the use of cognitive behavioral therapy (CBT) skills in working adults with mild-to-moderate depression. It was hypothesized that MoodHacker users would experience reduced depression symptoms and negative cognitions, and increased behavioral activation, knowledge of depression, and functioning in the workplace. METHODS: A parallel two-group randomized controlled trial was conducted with 300 employed adults exhibiting mild-to-moderate depression. Participants were recruited from August 2012 through April 2013 in partnership with an EAP and with outreach through a variety of additional non-EAP organizations. Participants were blocked on race/ethnicity and then randomly assigned within each block to receive, without clinical support, either the MoodHacker intervention (n=150) or alternative care consisting of links to vetted websites on depression (n=150). Participants in both groups completed online self assessment surveys at baseline, 6 weeks after baseline, and 10 weeks after baseline. Surveys assessed (1) depression symptoms, (2) behavioral activation, (3) negative thoughts, (4) worksite outcomes, (5) depression knowledge, and (6) user satisfaction and usability. After randomization, all interactions with subjects were automated with the exception of safety-related follow-up calls to subjects reporting current suicidal ideation and/or severe depression symptoms. RESULTS: At 6-week follow-up, significant effects were found on depression, behavioral activation, negative thoughts, knowledge, work productivity, work absence, and workplace distress. MoodHacker yielded significant effects on depression symptoms, work productivity, work absence, and workplace distress for those who reported access to an EAP, but no significant effects on these outcome measures for those without EAP access. Participants in the treatment arm used the MoodHacker app an average of 16.0 times (SD 13.3), totaling an average of 1.3 hours (SD 1.3) of use between pretest and 6-week follow-up. Significant effects on work absence in those with EAP access persisted at 10-week follow-up. CONCLUSIONS: This randomized effectiveness trial found that the MoodHacker app produced significant effects on depression symptoms (partial eta(2) = .021) among employed adults at 6-week follow-up when compared to subjects with access to relevant depression Internet sites. The app had stronger effects for individuals with access to an EAP (partial eta(2) = .093). For all users, the MoodHacker program also yielded greater improvement on work absence, as well as the mediating factors of behavioral activation, negative thoughts, and knowledge of depression self-care. Significant effects were maintained at 10-week follow-up for work absence. General attenuation of effects at 10-week follow-up underscores the importance of extending program contacts to maintain user engagement. This study suggests that light-touch, CBT-based mobile interventions like MoodHacker may be appropriate for implementation within EAPs and similar environments. In addition, it seems likely that supporting MoodHacker users with guidance from counselors may improve effectiveness for those who seek in-person support. TRIAL REGISTRATION: ClinicalTrials.gov NCT02335554; https://clinicaltrials.gov/ct2/show/NCT02335554 (Archived by WebCite at http://www.webcitation.org/6dGXKWjWE). PMID- 26813739 TI - Impact of Enhanced External Counterpulsation on Heart Failure Rehospitalization in Patients With Ischemic Cardiomyopathy. AB - Heart failure (HF) affects millions of Americans and causes financial burdens because of the need for rehospitalization. For this reason, health care systems and patients alike are seeking methods to decrease readmissions. We assessed the potential for reducing readmissions of patients with postacute care HF through an educational program combined with enhanced external counterpulsation (EECP). We examined 99 patients with HF who were referred to EECP centers and received heart failure education and EECP treatment within 90 days of hospital discharge from March 2013 to January 2015. We compared observed and predicted 90-day readmission rates and examined results of 6-minute walk tests, Duke Activity Status Index, New York Heart Association classification, and Canadian Cardiovascular Society classification before and after EECP. Patients were treated with EECP at a median augmentation pressure of 280 mm Hg (quartile 1 = 240, quartile 3 = 280), achieved as early as the first treatment. Augmentation ratios varied from 0.4 to 1.9, with a median of 1.0 (quartile 1 = 0.8, quartile 3 = 1.2). Only 6 patients (6.1%) had unplanned readmissions compared to the predicted 34%, p <0.0001. The average increase in distance walked was 52 m (18.4%), and the median increase in Duke Activity Status Index was 9.95 points (100%), p values <0.0001. New York Heart Association and Canadian Cardiovascular Society classes improved in 61% and 60% of the patients, respectively. In conclusion, patients with HF who received education and EECP within 90 days of discharge had significantly lower readmission rates than predicted, and improved functional status, walk distance, and symptoms. PMID- 26813740 TI - Radiotherapy for prostate cancer and sexual health. AB - Sexual dysfunction is very common after treatment of prostate cancer. Radiation therapy together with radical prostatectomy is the most effective treatment for localized disease. Percentages of erectile dysfunction (ED) reported in prospective studies after external-beam radiotherapy (RT) vary from 60-70%, and these are similar after brachytherapy. In randomized trials more realistic percentages of 30-40% are reported. Modern techniques do not seem to decrease post-radiation ED. No final conclusions can be drawn whether or not the radiation dose to the penile structures correlates with post-radiation ED in patients treated for prostate cancer. The etiology of ED after RT of prostate cancer is most probably multi-factorial. The phosphodiesterase type 5 inhibitors (PDE5-I) sildenafil and tadalafil have been shown to be effective to treat post-radiation ED in about half of the patients in randomized trials. Patients and their partners need to be adequately counselled on the effects of cancer treatment on their sexual life and relationship, and about the different treatment possibilities. Sexual counselling has not become yet a routine part of oncology care in most hospitals, but this should be provided. Due to the lack of robust data, prevention of post-radiation ED with PDE5-I cannot be recommended so far. PMID- 26813741 TI - "Intrinsic" correlations and their temporal evolutions between winter-time PNA/EPW and winter drought in the west United States. AB - In this study, relations between winter-time Pacific-Northern America pattern (PNA)/East Pacific wave-train (EPW) and winter-time drought in the west United States over the period of 1951-2010 are analyzed. Considering traditional Pearson's Correlation Coefficient can be influenced by non-stationarity and nonlinearity, a recently proposed method, Detrended Partial-Cross-Correlation Analysis (DPCCA) is applied. With DPCCA, we analyzed the "intrinsic" correlations between PNA/EPW and the winter drought with possible effects of ENSO and PDO removed. We found, i) significant negative correlations between PNA/EPW and drought on time scales of 5-6 years after removing the effects of ENSO, ii) and significant negative correlations between PNA/EPW and drought on time scales of 15-25 years after removing the effects of PDO. By further studying the temporal evolutions of the "intrinsic" correlations, we found on time scales of 5-6 years, the "intrinsic" correlations between PNA/EPW and drought can vary severely with time, but for most time, the correlations are negative. While on interdecadal (15 25 years) time scales, after the effects of PDO removed, unlike the relations between PNA and drought, the "intrinsic" correlations between EPW and drought takes nearly homogeneous-sign over the whole period, indicating a better model can be designed by using EPW. PMID- 26813742 TI - Partner Meeting Contexts and Risky Behavior in College Students' Other-Sex and Same-Sex Hookups. AB - We analyzed a sample of 12,065 hookup encounters among college students at 22 colleges and universities in the Online College Social Life Survey (OCSLS) to explore how partner meeting locales may influence college students' risky behavior when hookup partners are met in those contexts. For other-sex encounters, meeting in bars or at parties, through common interest groups or history, and (for women) at dormitories was associated with binge drinking during encounters, while meeting online and (for women) in public was associated with reduced binge drinking during encounters. Unprotected sex during other-sex encounters was more common when partners were met in public and less common with partners met in dormitories. Binge drinking and marijuana use during or just prior to encounters was associated with an increased risk of unprotected sex and other substance use. Marijuana use and unprotected sex during encounters was more common when students knew their hookup partner better or had hooked up with the partner before, while binge drinking was associated with hooking up with less familiar partners. Associations of meeting contexts with behavior were explained by the locale's association with institutional and personal trust, social scripts, and selection into certain contexts by students with a risk-taking personality. PMID- 26813743 TI - ST09, a Novel Thioester Derivative of Tacrine, Alleviates Cognitive Deficits and Enhances Glucose Metabolism in Vascular Dementia Rats. AB - AIMS: Chemical entities containing mercapto group have been increasingly attractive in the therapy of central nerve system (CNS) diseases. In the recent study, we screened a series of mercapto-tacrine derivatives with synergistic neuropharmacological profiles in vitro. METHODS: We investigated the effect and mechanism of ST09, a thioester derivative of tacrine containing a potential mercapto group, on the vascular dementia (VaD) model of rat induced by bilateral common carotid arteries occlusion (2-VO). RESULTS: ST09 and its active metabolite ST10 retained excellent inhibition on acetylcholinesterase (AChE) activity. ST09 significantly attenuated the 2-VO-induced impairment in spatial acquisition performance and inhibited the 2-VO-induced rise of AChE activity. In the VaD model, ST09 attenuated the oxidative stress and decreased the apoptosis in the cortex and hippocampus. Compared with donepezil, ST09 exhibited a better effect on the regeneration of free thiols in 2-VO rats. Interestingly, ST09, not donepezil, greatly improved glucose metabolism in various brain regions of 2-VO rats using functional imaging of (18) F-labeled fluoro-deoxyglucose (FDG) positron emission tomography (PET). CONCLUSIONS: ST09 may serve as a more promising agent for the therapy of VaD than tacrine owing to the introduction of a potential mercapto group into the parent skeleton. PMID- 26813744 TI - High Expression of Intestinal Homing Receptor CD103 in Adult T-Cell Leukemia/Lymphoma, Similar to 2 Other CD8+ T-Cell Lymphomas. AB - We investigated the expression of the alphaEbeta7 integrin (CD103)-intestinal homing receptor of T-intraepithelial lymphocytes (IELs) in 130 cases of adult T cell leukemia/lymphoma (ATLL). We detected CD103 lymphoma cells in 55% (31/56) of mainly gastrointestinal (GI)-involved ATLL cases. Among them, lymphoma cells of 18 cases located in other involved organs had similar CD103 expression patterns. Histologically, we found (a) increased reactive IELs in non-neoplastic mucosal layers in 28% (5/18) of surgical and mucosal resection cases, (b) preserved epithelial glands, and (c) numerous small intraepithelial ATLL nests in involved lesions in 36 (69%) and 21 (40%), respectively, of the 52 examined cases. These 3 patterns were common in intestinal type II enteropathy-associated T-cell lymphoma but were rare in intestinal EBV nasal-type/like T/natural killer (NK)-cell lymphoma. We detected CD103 tumor cells in 41% (16/39) of lymph node-involved ATLL, in 31% (11/35) of skin-involved ATLL, in 68% (21/31) of type II CD4 enteropathy-associated T-cell lymphoma cases, in 36% (8/22) of primary gastric T/NK-cell lymphomas, and in 77% (7/9) of CD8 epidermotropic mycosis fungoides. CD103 ATLL prefers involving the GI tract over the skin (P<0.05). CD103 expression in GI-involved and/or total ATLL cases was significantly higher than in other 9 T/NK-cell lymphoma groups (P<0.05 or 0.01). Only ATLL cases were commonly CD103 in CD4 T/NK-cell lymphoma groups (P<0.05 or 0.01). Human T lymphotropic virus-1-infected CD103 T-IELs and mucosal T cells may be important sources of ATLL. PMID- 26813746 TI - Intestinal Metaplasia is Present in Most if Not All Patients Who Have Undergone Endoscopic Mucosal Resection for Esophageal Adenocarcinoma. AB - Barrett esophagus is presently defined in the United States by the presence of intestinal metaplasia in columnar-lined esophagus based on the premise that the risk for adenocarcinoma depends on the presence of intestinal metaplasia. Recently, arguments have been made that nonintestinalized cardiac epithelium is also at risk and should be included in the definition of Barrett esophagus, as it is in England and Japan. One of these arguments is that residual intestinal metaplasia is frequently absent around early adenocarcinomas removed by endoscopic mucosal resection (EMR). We reviewed 27 EMRs performed in 21 patients. Residual intestinal metaplasia was absent in 10/27 (37%) EMR specimens. An in depth study of these 10 cases showed that 3 had intestinal metaplasia in a concurrent second EMR specimen, 4 had intestinal metaplasia in prior biopsy material available in our unit, and 2 had intestinal metaplasia in an esophagectomy that followed the EMR. The single patient in whom no intestinal metaplasia was found, neither in biopsies nor in EMR, and who did not undergo an esophagectomy had been under surveillance for Barrett esophagus for over 20 years. We conclude that the frequent absence of residual intestinal metaplasia around an adenocarcinoma in an EMR specimen is the result of sampling error. When evaluated in depth by looking at history, biopsies preceding the EMR, and esophagectomy following the EMR, all of these patients with adenocarcinoma had intestinal metaplasia in their columnar-lined esophagus. This indicates that intestinal metaplasia is a necessary precursor to adenocarcinoma of the esophagus. PMID- 26813747 TI - Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Ovary: Incidence and Morphologic Associations in 109 Cases. AB - Several morphologic features have been reported to be predictive of abnormal expression of mismatch repair (MMR) proteins in endometrial and colon carcinomas. Although it is known that abnormal MMR expression is increased in frequency in ovarian endometrioid and clear cell carcinomas, no such histologic correlation has been identified. We reviewed 109 unselected ovarian clear cell carcinomas for specific tumor characteristics (architecture, nuclear atypia, signet ring cells, stromal hyalinization, background precursor) and inflammatory response (peritumoral lymphocytes found along the leading edge of the tumor, intratumoral stromal inflammation found within the tumor, percentage of plasma cells in the intratumoral stromal inflammation, tumor-infiltrating lymphocytes) and performed immunohistochemistry for all 4 MMR proteins. Abnormal MMR expression was identified in 6% of tumors and included MSH2/MSH6 (3), MLH1/PMS2 (1), MSH6 (1), and PMS2 (1). These patients had a mean age of 40 (range, 31 to 48) years, which contrasted with a mean of 53.2 (range, 28 to 82) years for the overall cohort. One had a concurrent diagnosis of endometrial carcinoma, whereas another had a family history of endometrial carcinoma. None had a personal/family history of colonic carcinoma. Tumors with diffuse intratumoral stromal inflammation and peritumoral lymphocytes were more frequently associated with MMR loss on univariate analysis (P<0.001 and 0.047, respectively) with diffuse intratumoral stromal inflammation remaining a significant independent predictor on multivariate analysis. None of the other morphologic features evaluated reached statistical significance. Although previous series have been unable to identify a relationship between histology and MMR expression, this study identified a correlation with diffuse intratumoral stromal inflammation and peritumoral lymphocytes, 2 features that potentially could be selected for MMR analysis if corroborated by other studies. PMID- 26813749 TI - Various diagnostic criteria for atopic dermatitis (AD): A proposal of Reliable Estimation of Atopic Dermatitis in Childhood (REACH) criteria, a novel questionnaire-based diagnostic tool for AD. AB - Atopic dermatitis (AD) is a heterogeneous disease that manifests with a wide variety of clinical symptoms and signs. Due to the lack of definitive biomarkers for AD, it is very difficult to set up standard diagnostic criteria for AD which cover the entire spectrum of AD patients. Various instruments have been proposed for AD diagnosis, and they can be classified into a hospital setting or a community setting. From the preventive medicine viewpoint, questionnaire-based diagnostic criteria in a community setting are important to detect and manage childhood AD patients properly. In this article, various diagnostic criteria for AD in hospital and community settings will be reviewed. Additionally, the Reliable Estimation of Atopic Dermatitis in Childhood (REACH), a new full questionnaire-based diagnostic tool for childhood AD, will be reviewed. PMID- 26813750 TI - Measurement Properties of the Lower Extremity Functional Scale: A Systematic Review. AB - STUDY DESIGN: Systematic review of measurement properties. BACKGROUND: Many primary studies have examined the measurement properties, such as reliability, validity, and sensitivity to change, of the Lower Extremity Functional Scale (LEFS) in different clinical populations. A systematic review summarizing these properties for the LEFS may provide an important resource. OBJECTIVE: To locate and synthesize evidence on the measurement properties of the LEFS and to discuss the clinical implications of the evidence. METHODS: A literature search was conducted in 4 databases (PubMed, MEDLINE, Embase, and CINAHL), using predefined search terms. Two reviewers performed a critical appraisal of the included studies using a standardized assessment form. RESULTS: A total of 27 studies were included in the review, of which 18 achieved a very good to excellent methodological quality level. The LEFS scores demonstrated excellent test-retest reliability (intraclass correlation coefficients ranging between 0.85 and 0.99) and demonstrated the expected relationships with measures assessing similar constructs (Pearson correlation coefficient values of greater than 0.7). The responsiveness of the LEFS scores was excellent, as suggested by consistently high effect sizes (greater than 0.8) in patients with different lower extremity conditions. Minimal detectable change at the 90% confidence level (MDC90) for the LEFS scores varied between 8.1 and 15.3 across different reassessment intervals in a wide range of patient populations. The pooled estimate of the MDC90 was 6 points and the minimal clinically important difference was 9 points in patients with lower extremity musculoskeletal conditions, which are indicative of true change and clinically meaningful change, respectively. CONCLUSION: The results of this review support the reliability, validity, and responsiveness of the LEFS scores for assessing functional impairment in a wide array of patient groups with lower extremity musculoskeletal conditions. PMID- 26813748 TI - Magnetic Resonance Spectroscopy discriminates the response to microglial stimulation of wild type and Alzheimer's disease models. AB - Microglia activation has emerged as a potential key factor in the pathogenesis of Alzheimer's disease. Metabolite levels assessed by magnetic resonance spectroscopy (MRS) are used as markers of neuroinflammation in neurodegenerative diseases, but how they relate to microglial activation in health and chronic disease is incompletely understood. Using MRS, we monitored the brain metabolic response to lipopolysaccharides (LPS)-induced microglia activation in vivo in a transgenic mouse model of Alzheimer's disease (APP/PS1) and healthy controls (wild-type (WT) littermates) over 4 hours. We assessed reactive gliosis by immunohistochemistry and correlated metabolic and histological measures. In WT mice, LPS induced a microglial phenotype consistent with activation, associated with a sustained increase in macromolecule and lipid levels (ML9). This effect was not seen in APP/PS1 mice, where LPS did not lead to a microglial response measured by histology, but induced a late increase in the putative inflammation marker myoinositol (mI) and metabolic changes in total creatine and taurine previously reported to be associated with amyloid load. We argue that ML9 and mI distinguish the response of WT and APP/PS1 mice to immune mediators. Lipid and macromolecule levels may represent a biomarker of activation of healthy microglia, while mI may not be a glial marker. PMID- 26813751 TI - The Relationship Between Landing Sound, Vertical Ground Reaction Force, and Kinematics of the Lower Limb During Drop Landings in Healthy Men. AB - STUDY DESIGN: Controlled laboratory study, cross-sectional. BACKGROUND: Soft landing instruction, which is advocated in several injury prevention programs, is thought to have a qualitative relationship with decreased vertical ground reaction forces (vGRFs) and increased lower-limb joint excursions. OBJECTIVE: To quantify the relationships among landing sound, vGRFs, and lower-limb kinematics during a drop-landing task. METHODS: Twenty-six asymptomatic men aged 18 to 35 years were asked to perform 15 single-leg drop landings from a 30-cm height. Five trials were collected under 3 sound conditions: normal, quiet, and loud. The vGRF, lower-limb kinematics (sagittal plane), and impact sound were recorded during the deceleration phase. RESULTS: A simple linear regression revealed a significant relationship between landing sound and vGRF (R(2) = 0.42, P<.001). A repeated-measures analysis of variance showed that ankle and knee excursion significantly increased by 7.0 degrees and 11.7 degrees , respectively, during quiet landing (compared to normal landing; P<.001). During the loud landing condition, ankle joint excursion significantly decreased by 9.4 degrees compared to the normal landing condition (P<.001), and hip joint excursion significantly increased by 4.0 degrees compared to normal landing condition (P<.045). CONCLUSION: As landing sound decreases, so does vGRF during a drop-landing task. These reductions were achieved by increasing ankle and knee joint excursions. Conversely, as the landing sound increases, so does vGRF. This was the result of decreasing ankle joint excursion and increasing hip joint excursion. PMID- 26813745 TI - Barrett's Esophagus: A Comprehensive and Contemporary Review for Pathologists. AB - This review provides a summary of our current understanding of, and the controversies surrounding, the diagnosis, pathogenesis, histopathology, and molecular biology of Barrett's esophagus (BE) and associated neoplasia. BE is defined as columnar metaplasia of the esophagus. There is worldwide controversy regarding the diagnostic criteria of BE, mainly with regard to the requirement to histologically identify goblet cells in biopsies. Patients with BE are at increased risk for adenocarcinoma, which develops in a metaplasia-dysplasia carcinoma sequence. Surveillance of patients with BE relies heavily on the presence and grade of dysplasia. However, there are significant pathologic limitations and diagnostic variability in evaluating dysplasia, particularly with regard to the more recently recognized unconventional variants. Identification of non-morphology-based biomarkers may help risk stratification of BE patients, and this is a subject of ongoing research. Because of recent achievements in endoscopic therapy, there has been a major shift in the treatment of BE patients with dysplasia or intramucosal cancer away from esophagectomy and toward endoscopic mucosal resection and ablation. The pathologic issues related to treatment and its complications are also discussed in this review article. PMID- 26813752 TI - Development of a Risk Stratification Model for Delayed Inpatient Recovery of Physical Activities in Patients Undergoing Total Hip Replacement. AB - STUDY DESIGN: Prospective cohort design using data derived from usual care. BACKGROUND: It is important that patients are able to function independently as soon as possible after total hip replacement. However, the speed of regaining activities differs significantly. OBJECTIVES: To develop a risk stratification model (RSM) to predict delayed inpatient recovery of physical activities in people who underwent total hip replacement surgery. METHODS: This study was performed in 2 routine orthopaedic settings: Diakonessenhuis Hospital (setting A) and Nij Smellinghe Hospital (setting B). Preoperative screening was performed for all consecutive patients. In-hospital recovery of activities was assessed with the Modified Iowa Level of Assistance Scale. Delayed inpatient recovery of activities was defined as greater than 5 days. The RSM, developed using logistic regression analysis and bootstrapping, was based on data from setting A (n = 154). External validation was performed on the data set from setting B (n = 271). RESULTS: Twenty-one percent of the patients in setting A had a delayed recovery of activities during their hospital stay. Multivariable logistic regression modeling yielded a preliminary RSM that included the following factors: male sex (odds ratio [OR] = 0.8; 95% confidence interval [CI]: 0.2, 2.6), 70 or more years of age (OR = 1.2; 95% CI: 0.4, 3.4), body mass index of 25 kg/m(2) or greater (OR = 2.2; 95% CI: 0.7, 7.4), an American Society of Anesthesiologists score of 3 (OR = 1.2; 95% CI: 0.3, 4.4), a Charnley score of B or C (OR = 6.1; 95% CI: 2.2, 17.4), and a timed up-and-go score of 12.5 seconds or greater (OR = 3.1; 95% CI: 1.1, 9.0). The area under the receiver operating characteristic (ROC) curve was 0.82 (95% CI: 0.74, 0.90) and the Hosmer-Lemeshow test score was 3.57 (P>.05). External validation yielded an area under the ROC curve of 0.71 (95% CI: 0.61, 0.81). CONCLUSION: We demonstrated that the risk for delayed recovery of activities during the hospital stay can be predicted by using preoperative data. Level of Evidence Prognosis, level 1b. PMID- 26813753 TI - The Immediate Effects of Different Types of Ankle Support Introduced 6 Weeks After Surgical Internal Fixation for Ankle Fracture on Gait and Pain: A Randomized Crossover Trial. AB - STUDY DESIGN: Randomized 3-treatment, 3-period crossover trial. BACKGROUND: There is variation in clinical practice regarding the type of ankle support used to aid recovery after ankle fracture internal fixation surgery. OBJECTIVE: To determine the immediate effects of different ankle supports commonly issued to patients 6 weeks after surgery. METHODS: Participants were 18 adults, 6 weeks after internal fixation for transsyndesmotic/infrasyndesmotic fracture, in a major trauma center in the UK. Interventions were a stirrup brace and walker boot compared with Tubigrip. Outcomes were (1) step-length and single-limb support time asymmetry (percentage comparing injured and uninjured limbs), (2) step width, (3) gait velocity, and (4) pain during walking (visual analog scale, 0-100). RESULTS: Participants (mean +/- SD age, 47 +/- 14 years) included 8 women and 10 men, 6 weeks after surgical internal fixation for ankle fracture. Single-limb support time asymmetry reduced by 3% (95% confidence interval [CI]: 0%, 6%; P = .02) in the stirrup brace and by 5% (95% CI: 2%, 7%; P = .001) in the walker boot compared with Tubigrip. Step width was 1.2 cm (95% CI: 0.6, 1.7; P<.001) wider in the walker boot than in Tubigrip. Self-reported pain was lower in the walker boot (5/100) and in the stirrup brace (13/100) compared to the Tubigrip (18/100, P = .03). No significant differences were found in the effects of the supports on step-length asymmetry between the walker boot or stirrup brace and Tubigrip. CONCLUSION: At 6 weeks after surgical internal fixation for ankle fracture, pain and single-limb support time asymmetry over a short distance and for a short-term walk were immediately reduced with the use of a walker boot use and, to a lesser extent, a stirrup-brace compared to Tubigrip. Step width also widened in a walker boot, which may confer some additional gait stability. These results apply to immediate effects, so studies with longer-term follow-up are now indicated. The trial was registered at http://www.isrctn.com/ (ISRCTN84536917). Level of Evidence Therapy, level 2b. PMID- 26813754 TI - Plantar Cutaneous Sensitivity With and Without Cognitive Loading in People With Chronic Ankle Instability, Copers, and Uninjured Controls. AB - STUDY DESIGN: Controlled laboratory study. BACKGROUND: Deficits in light touch have recently been identified on the plantar surface of the foot in those with chronic ankle instability (CAI) but not in uninjured controls. It is unknown whether copers display similar deficits. Similarly, cognitive loading has been shown to impact postural control in different populations, but it is unclear how it may impact sensory perception. OBJECTIVES: To evaluate the difference in cutaneous sensation thresholds at rest and under cognitive loading, using Semmes Weinstein monofilaments (SWMs), among uninjured controls, copers, and those with CAI. METHODS: A total of 45 participants (mean +/- SD age, 20.2 +/- 2.8 years; height, 167.6 +/- 9.9 cm; mass, 66.3 +/- 14.7 kg) were recruited and categorized to a CAI, coper, or control group, based on Ankle Instability Instrument scores. Participants were assessed with SWMs for cutaneous thresholds using a 4-2-1 stepping algorithm at the head of the first metatarsal, base of the fifth metatarsal, calcaneus, and sinus tarsi. Each participant was then retested while generating random digits to the beat of a metronome in order to simulate cognitive loading. RESULTS: Participants with CAI displayed significantly higher SWM thresholds at the head of the first metatarsal, base of the fifth metatarsal, and sinus tarsi than those of the control participants, and significantly higher thresholds at the base of the fifth metatarsal and calcaneus than those of copers (all, P<.05). Copers showed higher thresholds than those of controls at the sinus tarsi only (P<.05). A main effect of cognitive loading was identified at all 4 sites (P<.05). CONCLUSION: People with CAI have deficits in plantar sensation relative to controls and copers. Cognitive loading increases plantar cutaneous sensation thresholds irrespective of CAI status. PMID- 26813755 TI - The Effectiveness of Mechanical Traction Among Subgroups of Patients With Low Back Pain and Leg Pain: A Randomized Trial. AB - STUDY DESIGN: Randomized clinical trial. Background The recommended initial management strategy for patients with low back pain and signs of nerve root compression is conservative treatment, but there is little evidence to guide the most appropriate management strategy. Preliminary research suggests that a treatment protocol of mechanical traction and extension-oriented exercises may be effective, particularly in a specific subgroup of patients. OBJECTIVE: To examine the effectiveness of mechanical traction in patients with lumbar nerve root compression and within a predefined subgroup. METHODS: One hundred twenty patients with low back pain with nerve root compression were recruited from physical therapy clinics. Using predefined subgrouping criteria, patients were stratified at baseline and randomized to receive an extension-oriented treatment approach with or without the addition of mechanical traction. During a 6-week period, patients received up to 12 treatment visits. Primary outcomes of pain and disability were collected at 6 weeks, 6 months, and 1 year by assessors blinded to group allocation. Outcomes were examined using linear mixed-model analyses examining change over time by treatment and the interaction between treatment and subgrouping status. RESULTS: The mean +/- SD age of participants was 41.1 +/- 11.3 years, median duration of symptoms was 62 days, and 57% were male. No significant differences in disability or pain outcomes were noted between treatment groups at any time point, nor was any interaction found between subgroup status and treatment. CONCLUSION: Patients with lumbar nerve root compression presenting for physical therapy can expect significant changes in disability and pain over a 6-week treatment period. There is no evidence that mechanical lumbar traction in combination with an extension-oriented treatment is superior to extension-oriented exercises alone in the management of these patients or within a predefined subgroup of patients. The study protocol was registered with ClinicalTrials.gov (NCT00942227). Level of Evidence Therapy, level 2b. PMID- 26813756 TI - Immediate Effect of Active Abdominal Contraction on Inter-recti Distance. AB - STUDY DESIGN: Controlled laboratory study. BACKGROUND: Inter-recti distance (IRD) is the measurement of the linear distance between the medial aspects of the rectus abdominis muscle. Inter-recti distance has been reported to decrease in postpartum women during a curl-up maneuver. OBJECTIVE: To determine if IRD decreases with active abdominal contraction in men and in nulliparous and parous women. METHODS: Fifty-six subjects (male, 11; nulliparous female, 22; parous female, 23) participated. Inter-recti distance was measured with the abdominal muscles at rest and during active contraction (curl-up), at 2 locations (above and below the umbilicus), using ultrasound imaging. A mixed-model, repeated measures analysis of covariance was used for each of the 2 locations, to determine whether IRD differed between contraction states among the 3 groups, with age and umbilicus circumference as covariates. When significant differences were found, planned t test comparisons were made. RESULTS: The parous group's IRD significantly decreased from rest to contraction at both locations, whereas the nulliparous and male groups' IRD did not significantly change from rest to contraction. The nulliparous group's IRD was significantly narrower than the other groups at rest at both locations, and narrower than the parous group during active contraction. CONCLUSION: Parous women had a narrower IRD in the curl-up condition than at rest, as hypothesized. However, an unexpected finding of a lack of significant within-group change in IRD in nulliparous women and men occurred. Findings suggest that the IRD in men may only differ from that of nulliparous women. PMID- 26813757 TI - The Influence of Centralization and Directional Preference on Spinal Control in Patients With Nonspecific Low Back Pain. AB - STUDY DESIGN: Prospective cohort, test-retest design. BACKGROUND: Directional preference (DP) with centralization (CEN) and DP without CEN are common pain pattern responses assessed by Mechanical Diagnosis and Therapy (MDT). Although there is evidence that MDT can reduce pain and disability in the short term by treating the patient with direction-specific exercises concordant with the patient's DP, the mechanism responsible for this is unclear. OBJECTIVE: To determine whether clinical signs of impaired spinal control improve immediately after eliciting a DP-with-CEN response or a DP-without-CEN response in patients with nonspecific low back pain. METHODS: Participants underwent a standardized MDT assessment and were classified into the following pain-pattern subgroups: DP with CEN, DP without CEN, or no DP. Clinical signs of impaired spinal control were assessed pre-MDT assessment and post-MDT assessment by an independent examiner. Four spinal control tests were conducted: aberrant lumbar movements while bending forward, the active straight leg raise (ASLR) test, the Trendelenburg test, and the prone instability test. Differences in spinal control pre-MDT assessment and post-MDT assessment were calculated for the 3 pain-pattern subgroups and compared with chi-square tests. We hypothesized that a larger proportion of patients in the DP-with-CEN subgroup would exhibit improved spinal control than patients categorized as DP without CEN or no DP. RESULTS: Of 114 patients recruited, 51 patients (44.7%) were categorized as DP with CEN, 23 (20.2%) as DP without CEN, and 40 (35.1%) as no DP. Before MDT assessment, between 28.9% (Trendelenburg test) and 63.7% (ASLR test) of patients showed impaired spinal control. After MDT assessment, a larger proportion of patients in the DP-with-CEN subgroup (43%) showed improvement than those in the no-DP subgroup (7%) on aberrant lumbar movements (P = .02). Likewise, more patients in the DP-with-CEN subgroup (50%) improved on the ASLR test than those in the no-DP subgroup (8%, P<.01) or the DP-without-CEN subgroup (7%, P = .01). Changes in Trendelenburg test and prone instability test outcomes did not reach statistical significance. CONCLUSION: Immediately following MDT assessment, a larger proportion of patients with a DP-with-CEN pain pattern showed improvement in clinical signs of spinal control compared to patients with a DP-without-CEN or no DP pain pattern. The current study was registered in the Dutch trial registry at http://www.trialregister.nl/trialreg/index.asp (NTR4246). LEVEL OF EVIDENCE: Therapy, level 2b. PMID- 26813758 TI - Where genome editing is needed. PMID- 26813759 TI - Co-occurrence of MYC amplification and TP53 mutations in human cancer. PMID- 26813760 TI - Reply: Co-occurrence of MYC amplification and TP53 mutations in human cancer. PMID- 26813761 TI - A proposed regulatory framework for genome-edited crops. PMID- 26813762 TI - Flavonols drive plant microevolution. AB - The idea that pollinators are in large part responsible for the diversity of flowering plants dates back more than 150 years to Darwin's work, but even modern scientists have struggled to identify specific 'speciation genes' and determine how they influenced flower-pollinator interactions. A new study proposes that a series of mutations in a single gene controlling floral chemicals influenced pollinator preferences, likely resulting in speciation, bringing us closer to finding a speciation gene. PMID- 26813763 TI - Hybridization speeds up the emergence and evolution of a new pathogen species. AB - Plant pathogens can evolve new host specificities and overcome host resistances over surprisingly few generations, a process that is greatly accelerated by agricultural practices. A new study provides a striking example in which the rapid emergence of a new pathogen via introgressive hybridization mirrors the evolution of a hybrid cereal crop. PMID- 26813764 TI - Legionella effectors reflect strength in diversity. AB - The Legionella genus includes opportunistic human pathogenic species that invade human cells using effector proteins that evolved during association with their natural amoeba hosts. A new study compares the genomes of 41 Legionella species to identify nearly 6,000 effectors, providing insight into these species' evolution and pathogenic lifestyles. PMID- 26813765 TI - Retraction: A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function. PMID- 26813766 TI - Zika virus outbreaks prompt warnings to pregnant women. PMID- 26813767 TI - Preparation of pH-sensitive zwitterionic nano micelles and drug controlled release for enhancing cellular uptake. AB - Zwitterionic copolymers have exhibited high resistance to nonspecific protein adsorption and have wide applications in drug delivery systems. Herein, a pH responsive poly(Lysine-alt-N,N'-bis(acryloyl) diaminohexane) was synthesized through the Michael addition polymerization between N, N'-bis(acryloyl) diaminohexane and lysine. Subsequently, nano micelles (NMs) were formed by self assembly of the copolymer in an aqueous solution. The NMs showed a slightly negative charge in blood environment, but a positively charged surface in extracellular pH of tumor. This feature could be used to enhance permeability and retention effect, and reinforce tumor cell uptake. Vitro release studies revealed that the release of DOX from the DOX-loaded NMs was evidently faster at pH 5.0 than at pH 7.4. MTT assays revealed that NMs were nontoxic. Thus, these smart NMs were feasible candidates and could be potentially used in cancer chemotherapy. PMID- 26813768 TI - Therapeutic Plasma Exchange-Does Age Matter? A Single-Center Study. AB - Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique designed for the removal of substances with large molecular weight from the plasma. However, it is not commonly performed in children and the elderly because of concern of potential complications. The Department of Nephrology at Zagreb University Hospital Centre's database (8335 procedures, 981 patients) was retrospectively analyzed from 1982 to 2011 to record indications, applications, and safety of TPE use in children (<=18 years), adults (>18 and <65 years), and elderly patients (>=65 years). Indications, blood access, replacement fluid, and anticoagulation during TPE differed among age groups. Significantly more complications were recorded in the youngest and eldest patients compared with the adults (12.2% and 12.7% vs. 9.9%, respectively), while the severity of complications did not differ significantly among the age groups. Our results indicate that TPE may be performed relatively safely in all age groups when the patients' differences are acknowledged prior to prescribing the procedure. PMID- 26813770 TI - Acute Respiratory and Renal Failure due to Hypermagnesemia, Induced by Counter Laxatives in an Elderly Man. PMID- 26813771 TI - An Unusual Cation-Binding Site and Distinct Domain-Domain Interactions Distinguish Class II Enolpyruvylshikimate-3-phosphate Synthases. AB - Enolpyruvylshikimate-3-phosphate synthase (EPSPS) catalyzes a critical step in the biosynthesis of a number of aromatic metabolites. An essential prokaryotic enzyme and the molecular target of the herbicide glyphosate, EPSPSs are the subject of both pharmaceutical and commercial interest. Two EPSPS classes that exhibit low sequence homology, differing substrate/glyphosate affinities, and distinct cation activation properties have previously been described. Here, we report structural studies of the monovalent cation-binding class II Coxiella burnetii EPSPS (cbEPSPS). Three cbEPSPS crystal structures reveal that the enzyme undergoes substantial conformational changes that alter the electrostatic potential of the active site. A complex with shikimate-3-phosphate, inorganic phosphate (Pi), and K(+) reveals that ligand induced domain closure produces an unusual cation-binding site bordered on three sides by the N-terminal domain, C terminal domain, and the product Pi. A crystal structure of the class I Vibrio cholerae EPSPS (vcEPSPS) clarifies the basis of differential class I and class II cation responsiveness, showing that in class I EPSPSs a lysine side chain occupies the would-be cation-binding site. Finally, we identify distinct patterns of sequence conservation at the domain-domain interface and propose that the two EPSPS classes have evolved to differently optimize domain opening-closing dynamics. PMID- 26813769 TI - Secreted Thrombospondin-1 Regulates Macrophage Interleukin-1beta Production and Activation through CD47. AB - Thrombospondin-1 regulates inflammation by engaging several cell surface receptors and by modulating activities of other secreted factors. We have uncovered a novel role of thrombospondin-1 in modulating production and activation of the proinflammatory cytokine IL-1beta by human and murine macrophages. Physiological concentrations of thrombospondin-1 limit the induction by lipopolysaccharide of IL-1beta mRNA and total protein production by human macrophages. This inhibition can be explained by the ability of thrombospondin-1 to disrupt the interaction between CD47 and CD14, thereby limiting activation of NFkappaB/AP-1 by lipopolysaccharide. Only the CD47-binding domain of thrombospondin-1 exhibits this activity. In contrast, CD47, CD36, and integrin binding domains of thrombospondin-1 independently enhance the inflammasome dependent maturation of IL-1beta in human THP-1 monocyte-derived macrophages. Correspondingly, mouse bone marrow-derived macrophages that lack either thrombospondin-1 or CD47 exhibit diminished induction of mature IL-1beta in response to lipopolysaccharide. Lack of CD47 also limits lipopolysaccharide induction of IL-1beta, NLRP3, and caspase-1 mRNAs. These data demonstrate that thrombospondin-1 exerts CD47-dependent and -independent pro-and anti-inflammatory effects on the IL-1beta pathway. Therefore, thrombospondin-1 and its receptor CD47 may be useful targets for limiting the pro-inflammatory effects of lipopolysaccharide and for treating endotoxemia. PMID- 26813772 TI - Invasive papillary carcinoma treated with neoadjuvant endocrine therapy in which pathological complete response was achieved. AB - BACKGROUND: Invasive papillary carcinoma is a rare type of invasive ductal carcinoma. Neoadjuvant endocrine therapy is now considered as an optional therapy for postmenopausal women with hormone receptor-positive breast cancers, including invasive papillary carcinoma. CASE PRESENTATION: We discuss the case of an 83 year-old postmenopausal Japanese female with hormone receptor-positive invasive papillary carcinoma who started treatment with an aromatase inhibitor and achieved pathological complete response after 12 months of endocrine treatment. CONCLUSION: Appropriate drugs and durations of neoadjuvant endocrine treatment have yet to be established. Continuing therapy with an aromatase inhibitor until the best clinical response is achieved may represent one of the best strategies in neoadjuvant endocrine therapy. PMID- 26813773 TI - IFN beta 1a as Glucocorticoids-Sparing Therapy in a Patient with CLIPPERS. AB - BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described inflammatory disease of the central nervous system, distinguished by brainstem- and spinal cord-centered lesions with a characteristic contrast enhancement on MRI, a lymphocytic perivascular infiltrate on pathological exam, and a dramatic response to and dependence on steroids therapy. Since its initial description in 2010, different glucocorticoid-sparing agents, mostly immunosuppressant drugs, have been used to minimize the dosage, but these therapies also carry the risk of important secondary effects. We present the first reported case of CLIPPERS treated with interferon beta 1a as add-on therapy. CASE REPORT: A previously healthy 31-year-old man presented with gait ataxia and dysarthria. MRI showed pons-centered hyperintense patchy lesions on T2-weighted images. Additional tests ruled out other possible diagnoses and symptoms reversed with intravenous methylprednisolone. Over the years the patient presented with several episodes of deterioration each year, which were partly reversed with glucocorticoid therapy, but leaving him with growing sequelae. Four years after the initial event, treatment with interferon-beta-1a was initiated, achieving reduced frequency of the relapses to 1 every 4 years, which were no longer associated to increasing disability. This allowed reducing glucocorticoids to 30 mg of Deflazacort every other day. CONCLUSIONS: Interferon beta-1a could be an alternative to corticosteroid-combined therapy in CLIPPERS and its more benign profile of secondary effects compared to immunosuppressants could make it an attractive choice. PMID- 26813774 TI - Nonclassical light from a large number of independent single-photon emitters. AB - Nonclassical quantum effects gradually reach domains of physics of large systems previously considered as purely classical. We derive a hierarchy of operational criteria suitable for a reliable detection of nonclassicality of light from an arbitrarily large ensemble of independent single-photon emitters. We show, that such large ensemble can always emit nonclassical light without any phase reference and under realistic experimental conditions including incoherent background noise. The nonclassical light from the large ensemble of the emitters can be witnessed much better than light coming from a single or a few emitters. PMID- 26813775 TI - Erratum to: Transitions between the Arabidopsis-type and the human-type telomere sequence in green algae (clade Caudivolvoxa, Chlamydomonadales). PMID- 26813776 TI - Autophagy and Alpha-Synuclein: Relevance to Parkinson's Disease and Related Synucleopathies. AB - Evidence from human postmortem material, transgenic mice, and cellular/animal models of PD link alpha-synuclein accumulation to alterations in the autophagy lysosomal pathway. Conversely, alpha-synuclein mutations related to PD pathogenesis, as well as post-translational modifications of the wild-type protein, result in the generation of aberrant species that may impair further the function of the autophagy lysosomal pathway, thus generating a vicious cycle leading to neuronal death. Moreover, PD-linked mutations in lysosomal-related genes, such as glucocerebrosidase, have been also shown to contribute to alpha synuclein accumulation and related toxicity, indicating that lysosomal dysfunction may, in part, account for the neurodegeneration observed in synucleinopathies. In the current review, we summarize findings related to the inter-relationship between alpha-synuclein and lysosomal proteolytic pathways, focusing especially on recent experimental strategies based on the manipulation of the autophagy lysosomal pathway to counteract alpha-synuclein-mediated neurotoxicity in vivo. Pinpointing the factors that regulate alpha-synuclein association to the lysosome may represent potential targets for therapeutic interventions in PD and related synucleinopathies. PMID- 26813777 TI - Reply to: "Recent Advances in Circumferential Tracheal Replacement and Transplantation". PMID- 26813778 TI - The effect of production system (barn and free-range), slaughtering age and gender on carcass traits and meat quality of partridges (Alectoris chukar). AB - 1. A total of 400 Alectoris chukar partridges were reared in either barn or free range production systems and slaughtered at 14, 16 or 18 weeks of age in order to determine the effects of production system, age and gender on carcass traits (live weight, carcass weight, carcass yield, carcass part and edible inner organ percentages at slaughtering) and meat quality (L*, a* and b* meat colour and pH). 2. Production system had a significant effect on both slaughter traits and meat quality. 3. Partridges raised in barn conditions had higher live weights and carcass weights whereas meat quality was better in birds raised in the free-range system. PMID- 26813779 TI - Evaluation of two instruments of perceived symptom intensity in palliative care patients in an outpatient clinic. AB - AIMS AND OBJECTIVES: To evaluate the test-retest stability in assessments of perceived symptom intensity on the Edmonton Symptom Assessment System-revised and the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core 15 Palliative. The possible interchangeability between the instruments and the patients' experiences of completing the instruments were also studied. BACKGROUND: The two instruments assess the same symptoms, but the symptom intensity is assessed on 11-point numerical scales on the Edmonton Symptom Assessment System-revised and on four-point verbal descriptive scales on the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core 15 Palliative. Both instruments are commonly used; however, uncertainty exists about which instrument should be recommended and about the interchangeability of the instruments. DESIGN: This study used a test-retest design with inter-scale comparisons. METHODS: Data from 54 patients with cancer who were receiving palliative care in an oncology outpatient clinic were self reported by the patients in the clinic, at home and when patients returned to the clinic. RESULTS: The assessments on the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core 15 Palliative verbal rating scales showed a higher level of test-retest stability than the assessments on the Edmonton Symptom Assessment System-revised numerical scoring scales, indicating higher reliability. The correspondence between the verbal categories and the numerical scores of symptom intensity were low because different verbal categories were used by patients who assessed the same numerical score. CONCLUSIONS: The test-retest stability in the assessments was higher on the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core 15 Palliative and the results show that assessments on the two instruments could not be used interchangeably. Therefore, the symptom instrument chosen must be specified and unchanged within a patient to improve efficacy in clinical practice. RELEVANCE TO CLINICAL PRACTICE: The Edmonton Symptom Assessment System-revised or the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core 15 Palliative can be used for initial assessments of patients, but should not be compared or used interchangeably. It is vitally important to have individual follow-up for all patients who score an instrument. PMID- 26813780 TI - A Stretchable Graphitic Carbon/Si Anode Enabled by Conformal Coating of a Self Healing Elastic Polymer. AB - A high-capacity stretchable graphitic carbon/Si foam electrode is enabled by a conformal self-healing elastic polymer coating. The composite electrode exhibits high stretchability (up to 88%) and endures 1000 stretching-releasing cycles at 25% strain with detrimental resistance increase. Meanwhile, the electrode delivers a high reversible specific capacity of 719 mA g(-1) and good cycling stability with 81% capacity retention after 100 cycles. PMID- 26813782 TI - An approach to scoring cursorial limb proportions in carnivorous dinosaurs and an attempt to account for allometry. AB - From an initial dataset of 53 theropod species, the general relationship between theropod lower-leg length and body mass is identified. After factoring out this allometric relationship, theropod hindlimb proportions are assessed irrespective of body mass. Cursorial-limb-proportion (CLP) scores derived for each of the considered theropod taxa offer a measure of the extent to which a particular species deviates in favour of higher or lower running speeds. Within the same theropod species, these CLP scores are found to be consistent across multiple adult specimens and across disparate ontogenetic stages. Early theropods are found to have low CLP scores, while the coelurosaurian tyrannosauroids and compsognathids are found to have high CLP scores. Among deinonychosaurs, troodontids have consistently high CLP scores, while many dromaeosaur taxa, including Velociraptor and Deinonychus, have low CLP scores. This indicates that dromaeosaurs were not, overall, a particularly cursorily adapted group. Comparisons between the CLP scores of Tyrannosaurus and specimens referred to the controversial genus Nanotyrannus indicate a strong discrepancy in cursorial adaptations, which supports the legitimacy of Nanotyrannus and the previous suggestions of ecological partitioning between Nanotyrannus and the contemporaneous Tyrannosaurus. PMID- 26813781 TI - Trends in Life Expectancy and Lifespan Variation by Educational Attainment: United States, 1990-2010. AB - The educational gradient in life expectancy is well documented in the United States and in other low-mortality countries. Highly educated Americans, on average, live longer than their low-educated counterparts, who have recently seen declines in adult life expectancy. However, limiting the discussion on lifespan inequality to mean differences alone overlooks other dimensions of inequality and particularly disparities in lifespan variation. The latter represents a unique form of inequality, with higher variation translating into greater uncertainty in the time of death from an individual standpoint, and higher group heterogeneity from a population perspective. Using data from the National Vital Statistics System from 1990 to 2010, this is the first study to document trends in both life expectancy and S25--the standard deviation of age at death above 25--by educational attainment. Among low-educated whites, adult life expectancy declined by 3.1 years for women and by 0.6 years for men. At the same time, S25 increased by about 1.5 years among high school-educated whites of both genders, becoming an increasingly important component of total lifespan inequality. By contrast, college-educated whites benefited from rising life expectancy and record low variation in age at death, consistent with the shifting mortality scenario. Among blacks, adult life expectancy increased, and S25 plateaued or declined in nearly all educational attainment groups, although blacks generally lagged behind whites of the same gender on both measures. Documenting trends in lifespan variation can therefore improve our understanding of lifespan inequality and point to diverging trajectories in adult mortality across socioeconomic strata. PMID- 26813783 TI - Suicide lethality scale: Concerns regarding validity and scoring. PMID- 26813785 TI - Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells. AB - Self-renewing tissue-resident macrophages are thought to be exclusively derived from embryonic progenitors. However, whether circulating monocytes can also give rise to such macrophages has not been formally investigated. Here we use a new model of diphtheria toxin-mediated depletion of liver-resident Kupffer cells to generate niche availability and show that circulating monocytes engraft in the liver, gradually adopt the transcriptional profile of their depleted counterparts and become long-lived self-renewing cells. Underlining the physiological relevance of our findings, circulating monocytes also contribute to the expanding pool of macrophages in the liver shortly after birth, when macrophage niches become available during normal organ growth. Thus, like embryonic precursors, monocytes can and do give rise to self-renewing tissue-resident macrophages if the niche is available to them. PMID- 26813786 TI - Apibacter mensalis sp. nov.: a rare member of the bumblebee gut microbiota. AB - Isolates LMG 28357T (=R-53146T) and LMG 28623 were obtained from gut samples of Bombus lapidarius bumblebees caught in Ghent, Belgium. They had identical 16S rRNA gene sequences which were 95.7 % identical to that of Apibacter adventoris wkB301T, a member of the family Flavobacteriaceae. Both isolates had highly similar matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS and randomly amplified polymorphic DNA (RAPD) profiles. A draft genome sequence was obtained for strain LMG 28357T (Gold ID Gp0108260); its DNA G+C content was 30.4%, which is within the range reported for members of the family Flavobacteriaceae (27 to 56 mol%) and which is similar to that of the type strain of A. adventoris (29.0 mol%). Whole-cell fatty acid methyl ester analysis of strain LMG 28357T revealed many branched-chain fatty acids, a typical characteristic of bacteria of the family Flavobacteriaceae and a profile that was similar to that reported for A. adventoris wkB301T. MK6 was the major respiratory quinone, again conforming to bacteria of the family Flavobacteriaceae. The isolates LMG 28357T and LMG 28623 could be distinguished from A. adventoris strains through their oxidase activity. On the basis of phylogenetic, genotypic and phenotypic data, we propose to classify both isolates as representatives of a novel species of the genus Apibacter, Apibacter mensalis sp. nov., with LMG 28357T (=DSM 100903T=R-53146T) as the type strain. PMID- 26813784 TI - Protein-Specific Differential Glycosylation of Immunoglobulins in Serum of Ovarian Cancer Patients. AB - Previous studies indicated that glycans in serum may serve as biomarkers for diagnosis of ovarian cancer; however, it was unclear to which proteins these glycans belong. We hypothesize that protein-specific glycosylation profiles of the glycans may be more informative of ovarian cancer and can provide insight into biological mechanisms underlying glycan aberration in serum of diseased individuals. Serum samples from women diagnosed with epithelial ovarian cancer (EOC, n = 84) and matched healthy controls (n = 84) were obtained from the Gynecologic Oncology Group. Immunoglobulin (IgG, IgA, and IgM) concentrations and glycosylation profiles were quantified using multiple reaction monitoring mass spectrometry. Differential and classification analyses were performed to identify aberrant protein-specific glycopeptides using a training set. All findings were validated in an independent test set. Multiple glycopeptides from immunoglubins IgA, IgG, and IgM were found to be differentially expressed in serum of EOC patients compared with controls. The protein-specific glycosylation profiles showed their potential in the diagnosis of EOC. In particular, IgG-specific glycosylation profiles are the most powerful in discriminating between EOC case and controls. Additional studies of protein- and site-specific glycosylation profiles of immunoglobulins and other proteins will allow further elaboration on the characteristics of biological functionality and causality of the differential glycosylation in ovarian cancer and thus ultimately lead to increased sensitivity and specificity of diagnosis. PMID- 26813787 TI - The effect of major income sources on rural household food (in)security: Evidence from Swaziland and implications for policy. AB - The aim of this article was to investigate the food (in)security effect of household income generated from major economic activities in rural Swaziland. From a sample of 979 households, the results of a multinomial treatment regression model indicated that gender of household head, labor endowment, education, size of arable land, and location significantly influenced the households' choice of primary economic activity. Further results suggested that off-farm-income-dependent households were less likely to be food insecure when compared with on-farm-income-dependent households. However, on-farm-income dependent households had a better food security status than their counterparts who depended on remittances and nonfarm economic activities. PMID- 26813788 TI - "Everyone else gets ice cream here more often than I do--It burns me up"- Perspectives on Diabetes Care from Nursing Home Residents and their Doctors. AB - BACKGROUND: To explore the perspectives of nursing home (NH) residents with diabetes and their doctors regarding the burdens of living with diabetes and diabetes treatments. METHODS: Qualitative study of nursing home residents aged 65 and older with diabetes (n = 14) and nursing home physicians (n = 9) at a Department of Veterans Affairs nursing home (known as the Community Living Center). A semi-structured interview was used to elicit nursing home residents' and physicians' perspectives on the burden of diabetes and diabetes treatments. Transcripts were analyzed using constant comparative methods. RESULTS: The mean age of the nursing home residents was 74; Most (93%) were male and 50% self identified themselves as white. The mean age of nursing home physicians was 39 and 55% were geriatricians. Dietary restrictions, loss of independence and fingersticks/insulin were noted to be the most burdensome aspects of diabetes. Nursing home residents with a more positive outlook were generally more engaged in their care, while nursing home residents with a more pessimistic outlook were less engaged, allowing their physicians to assume complete control of their care. While physicians noted the potential negative impact of dietary restrictions, nursing home residents' comments suggest that physicians underestimate the burden of dietary restrictions. CONCLUSIONS: Veterans Affairs nursing home residents were substantially burdened by their diabetes treatments, especially dietary restrictions and fingerstick monitoring. Since there is little evidence that dietary restrictions improve outcomes, fewer dietary restrictions may be appropriate and lead to lower treatment burdens for nursing home residents with diabetes. PMID- 26813789 TI - Appoptosin interacts with mitochondrial outer-membrane fusion proteins and regulates mitochondrial morphology. AB - Mitochondrial morphology is regulated by fusion and fission machinery. Impaired mitochondria dynamics cause various diseases, including Alzheimer's disease. Appoptosin (encoded by SLC25A38) is a mitochondrial carrier protein that is located in the mitochondrial inner membrane. Appoptosin overexpression causes overproduction of reactive oxygen species (ROS) and caspase-dependent apoptosis, whereas appoptosin downregulation abolishes beta-amyloid-induced mitochondrial fragmentation and neuronal death during Alzheimer's disease. Herein, we found that overexpression of appoptosin resulted in mitochondrial fragmentation in a manner independent of its carrier function, ROS production or caspase activation. Although appoptosin did not affect levels of mitochondrial outer-membrane fusion (MFN1 and MFN2), inner-membrane fusion (OPA1) and fission [DRP1 (also known as DNM1L) and FIS1] proteins, appoptosin interacted with MFN1 and MFN2, as well as with the mitochondrial ubiquitin ligase MITOL (also known as MARCH5) but not OPA1, FIS1 or DRP1. Appoptosin overexpression impaired the interaction between MFN1 and MFN2, and mitochondrial fusion. By contrast, co-expression of MFN1, MITOL and a dominant-negative form of DRP1, DRP1(K38A), partially rescued appoptosin-induced mitochondrial fragmentation and apoptosis, whereas co expression of FIS1 aggravated appoptosin-induced apoptosis. Together, our results demonstrate that appoptosin can interact with mitochondrial outer-membrane fusion proteins and regulates mitochondrial morphology. PMID- 26813790 TI - Molecular cytogenetic characterization of Dasypyrum breviaristatum chromosomes in wheat background revealing the genomic divergence between Dasypyrum species. AB - BACKGROUND: The uncultivated species Dasypyrum breviaristatum carries novel diseases resistance and agronomically important genes of potential use for wheat improvement. The development of new wheat-D. breviaristatum derivatives lines with disease resistance provides an opportunity for the identification and localization of resistance genes on specific Dasypyrum chromosomes. The comparison of wheat-D. breviaristatum derivatives to the wheat-D. villosum derivatives enables to reveal the genomic divergence between D. breviaristatum and D. villosum. RESULTS: The mitotic metaphase of the wheat- D. breviaristatum partial amphiploid TDH-2 and durum wheat -D. villosum amphiploid TDV-1 were studied using multicolor fluorescent in situ hybridization (FISH). We found that the distribution of FISH signals of telomeric, subtelomeric and centromeric regions on the D. breviaristatum chromosomes was different from those of D. villosum chromosomes by the probes of Oligo-pSc119.2, Oligo-pTa535, Oligo-(GAA)7 and Oligo-pHv62-1. A wheat line D2139, selected from a cross between wheat lines MY11 and TDH-2, was characterized by FISH and PCR-based molecular markers. FISH analysis demonstrated that D2139 contained 44 chromosomes including a pair of D. breviaristatum chromosomes which had originated from the partial amphiploid TDH 2. Molecular markers confirmed that the introduced D. breviaristatum chromosomes belonged to homoeologous group 7, indicating that D2139 was a 7V(b) disomic addition line. The D2139 displayed high resistance to wheat stripe rust races at adult stage plant, which may be inherited from, D. breviaristatum chromosome 7V(b). CONCLUSION: The study present here revealed that the large divergence between D. breviaristatum and D. villosum with respected to the organization of different repetitive sequences. The identified wheat- D. breviaristatum chromosome addition line D2139 will be used to produce agronomically desirable germplasm for wheat breeding. PMID- 26813791 TI - TFEB and TFE3 are novel components of the integrated stress response. AB - To reestablish homeostasis and mitigate stress, cells must activate a series of adaptive intracellular signaling pathways. The participation of the transcription factors TFEB and TFE3 in cellular adaptation to starvation is well established. Here, we show that TFEB and TFE3 also play an important role in the cellular response to ER stress. Treatment with ER stressors causes translocation of TFEB and TFE3 to the nucleus in a process that is dependent on PERK and calcineurin but not on mTORC1. Activated TFEB and TFE3 enhance cellular response to stress by inducing direct transcriptional upregulation of ATF4 and other UPR genes. Under conditions of prolonged ER stress, TFEB and TFE3 contribute to cell death, thus revealing an unexpected role for these proteins in controlling cell fate. This work evidences a broader role of TFEB and TFE3 in the cellular response to stress than previously anticipated and reveals an integrated cooperation between different cellular stress pathways. PMID- 26813792 TI - Natural variation in methane emission of sheep fed on a lucerne pellet diet is unrelated to rumen ciliate community type. AB - Only limited information is available on the roles of different rumen ciliate community types, first described by Eadie in 1962, in enteric methane (CH4) formation by their ruminant hosts. If the different types were differentially associated with CH4 formation, then ciliate community typing could be used to identify naturally high and low CH4-emitting animals. Here we measured the CH4 yields [g CH4 (kg feed dry matter intake, DMI)(-1)] of 118 sheep fed a standard pelleted lucerne diet at two different times, at least 2 weeks apart. There were significant differences (P < 2.2 * 10(-16), Wilcoxon rank sum test) in the CH4 yields (+/- sd) from sheep selected as high [16.7 +/- 1.5 g CH4 (kg DMI)(-1)] and low emitters [13.3 +/- 1.5 g CH4 (kg DMI)(-1)]. A rumen sample was collected after each of the two measurements, and ciliate composition was analysed using barcoded 454 Titanium pyrosequencing of 18S rRNA genes. The genera found, in order of mean relative abundance, were Epidinium, Entodinium, Dasytricha, Eudiplodinium, Polyplastron, Isotricha and Anoplodinium-Diplodinium, none of which was significantly correlated with the CH4 emissions ranking associated with the rumen sample. Ciliate communities naturally assembled into four types (A, AB, B and O), characterized by the presence and absence of key genera. There was no difference in CH4 yield between sheep that harboured different ciliate community types, suggesting that these did not underlie the natural variation in CH4 yields. Further research is needed to unravel the nature of interactions between ciliate protozoa and other rumen micro-organisms, which may ultimately lead to contrasting CH4 emission phenotypes. PMID- 26813793 TI - Combined Chlorophyll Fluorescence and Transcriptomic Analysis Identifies the P3/P4 Transition as a Key Stage in Rice Leaf Photosynthetic Development. AB - Leaves are derived from heterotrophic meristem tissue that, at some point, must make the transition to autotrophy via the initiation of photosynthesis. However, the timing and spatial coordination of the molecular and cellular processes underpinning this switch are poorly characterized. Here, we report on the identification of a specific stage in rice (Oryza sativa) leaf development (P3/P4 transition) when photosynthetic competence is first established. Using a combined physiological and molecular approach, we show that elements of stomatal and vascular differentiation are coordinated with the onset of measurable light absorption for photosynthesis. Moreover, by exploring the response of the system to environmental perturbation, we show that the earliest stages of rice leaf development have significant plasticity with respect to elements of cellular differentiation of relevance for mature leaf photosynthetic performance. Finally, by performing an RNA sequencing analysis targeted at the early stages of rice leaf development, we uncover a palette of genes whose expression likely underpins the acquisition of photosynthetic capability. Our results identify the P3/P4 transition as a highly dynamic stage in rice leaf development when several processes for the initiation of photosynthetic competence are coordinated. As well as identifying gene targets for future manipulation of rice leaf structure/function, our data highlight a developmental window during which such manipulations are likely to be most effective. PMID- 26813794 TI - The Wheat Mediator Subunit TaMED25 Interacts with the Transcription Factor TaEIL1 to Negatively Regulate Disease Resistance against Powdery Mildew. AB - Powdery mildew, caused by the biotrophic fungal pathogen Blumeria graminis f. sp. tritici, is a major limitation for the production of bread wheat (Triticum aestivum). However, to date, the transcriptional regulation of bread wheat defense against powdery mildew remains largely unknown. Here, we report the function and molecular mechanism of the bread wheat Mediator subunit 25 (TaMED25) in regulating the bread wheat immune response signaling pathway. Three homoalleles of TaMED25 from bread wheat were identified and mapped to chromosomes 5A, 5B, and 5D, respectively. We show that knockdown of TaMED25 by barley stripe mosaic virus-induced gene silencing reduced bread wheat susceptibility to the powdery mildew fungus during the compatible plant-pathogen interaction. Moreover, our results indicate that MED25 may play a conserved role in regulating bread wheat and barley (Hordeum vulgare) susceptibility to powdery mildew. Similarly, bread wheat ETHYLENE INSENSITIVE3-LIKE1 (TaEIL1), an ortholog of Arabidopsis (Arabidopsis thaliana) ETHYLENE INSENSITIVE3, negatively regulates bread wheat resistance against powdery mildew. Using various approaches, we demonstrate that the conserved activator-interacting domain of TaMED25 interacts physically with the separate amino- and carboxyl-terminal regions of TaEIL1, contributing to the transcriptional activation activity of TaEIL1. Furthermore, we show that TaMED25 and TaEIL1 synergistically activate ETHYLENE RESPONSE FACTOR1 (TaERF1) transcription to modulate bread wheat basal disease resistance to B. graminis f. sp. tritici by repressing the expression of pathogenesis-related genes and deterring the accumulation of reactive oxygen species. Collectively, we identify the TaMED25-TaEIL1-TaERF1 signaling module as a negative regulator of bread wheat resistance to powdery mildew. PMID- 26813796 TI - Letter to the editor about Maculopapular Rash after Penicillin Injection in a Patient with Confirmed Infectious Mononucleosis. PMID- 26813795 TI - Fast Estimation of Dietary Fiber Content in Apple. AB - Dietary fibers (DF) are one of the nutritional benefits of fleshy fruit consumption that is becoming a quality criterion for genetic selection by breeders. However, the AOAC total DF content determination is not readily amenable for screening large fruit collections. A new screening method of DF content in an apple collection based on the automated preparation of cell wall material as an alcohol-insoluble residue (AIR) is proposed. The yield of AIR from 27 apple genotypes was compared with DF measured according to AOAC method 985.29. Although residual protein content in AIRs did not affect DF measurement, subtraction of starch content above 3% dry weight in AIRs was needed to agree with AOAC measured DF. A fast colorimetric screening of starch in AIR was developed to detect samples needing correction. The proposed method may prove useful for the rapid determination of DF in collections of other fleshy fruit besides apple. PMID- 26813797 TI - Impacts of a Rapidly Declining Mountain Snowpack on Streamflow Timing in Canada's Fraser River Basin. AB - With its headwaters in the water towers of the western Cordillera of North America, the Fraser River is one of the continent's mightiest rivers by annual flows, supplies vital freshwater resources to populous downstream locations, and sustains the world's largest stocks of sockeye salmon along with four other salmon species. Here we show the Variable Infiltration Capacity (VIC) model's ability to reproduce accurately observed trends in daily streamflow for the Fraser River's main stem and six of its major tributaries over 1949-2006 when air temperatures rose by 1.4 degrees C while annual precipitation amounts remained stable. Rapidly declining mountain snowpacks and earlier melt onsets result in a 10-day advance of the Fraser River's spring freshet with subsequent reductions in summer flows when up-river salmon migrations occur. Identification of the sub basins driving the Fraser River's most significant changes provides a measure of seasonal predictability of future floods or droughts in a changing climate. PMID- 26813798 TI - Antifungal drugs combinations: a patent review 2000-2015. AB - INTRODUCTION: Combination therapy has emerged as an approach to improve the efficacy of antifungal drugs. Its main objective is to achieve synergistic interaction with higher antifungal properties and lower toxic effects than each substance alone. AREAS COVERED: Twenty-four patents disclosed in the period of 2000-2015 were covered in this review. Twenty of them were devoted to pharmacodynamic potentiation, while four were dedicated to pharmacokinetic actions. EXPERT OPINION: The common characteristic of most patents published in this area is that the main partner is a commercial antifungal drug. In the most innovative combinations the second component was either a modifier of proton homeostasis, an antibody, an inhibitor of the adhesion of epithelial or endothelial cells or a keratinolytic agent that improves the skin penetration. The evaluation of synergism is always made with simple in vitro methods, which constitutes a weakness of the disclosed patents, due to the lack of in vivo studies, since the in vitro tests cannot predict the in vivo behavior. Also, it is surprising that none of the patents analyze the toxicity of the new combinations, taking into account that one of the main objectives of the combinations is to reduce the toxicity of the existing antifungal drugs. PMID- 26813799 TI - Kounis syndrome secondary to intravenous cephalosporin administration. AB - Kounis syndrome is a clinical condition due to hypersensitivity that culminates into acute coronary syndrome (ACS) which can be fatal. A 36-year-old male with no conventional coronary risk factors presented elsewhere with a history of fever for 4 days, cough with expectoration, diarrhea and was treated with cephalosporin (Inj. Cefotaxime as an infusion) along with analgesics. He experienced generalized itching 5 minutes after cefotaxime infusion followed by sweating, headache, chest pain with facial and periorbital swelling for which he was rushed to our hospital. On examination he was afebrile with a low blood pressure. Electrocardiogram taken at an outside hospital revealed incomplete right bundle branch block and ST depression V3-V5. Investigations showed increase in troponin T. He was managed with anti-histamines and standard protocol for treatment of ACS. Coronary angiogram revealed normal coronaries. The patient improved symptomatically with treatment and was discharged on an anti-platelet, nitrate and a statin. PMID- 26813800 TI - Satellite gravity measurement monitoring terrestrial water storage change and drought in the continental United States. AB - We use satellite gravity measurements in the Gravity Recovery and Climate Experiment (GRACE) to estimate terrestrial water storage (TWS) change in the continental United States (US) from 2003 to 2012, and establish a GRACE-based Hydrological Drought Index (GHDI) for drought monitoring. GRACE-inferred TWS exhibits opposite patterns between north and south of the continental US from 2003 to 2012, with the equivalent water thickness increasing from -4.0 to 9.4 cm in the north and decreasing from 4.1 to -6.7 cm in the south. The equivalent water thickness also decreases by -5.1 cm in the middle south in 2006. GHDI is established to represent the extent of GRACE-inferred TWS anomaly departing from its historical average and is calibrated to resemble traditional Palmer Hydrological Drought Index (PHDI) in the continental US. GHDI exhibits good correlations with PHDI in the continental US, indicating its feasibility for drought monitoring. Since GHDI is GRACE-based and has minimal dependence of hydrological parameters on the ground, it can be extended for global drought monitoring, particularly useful for the countries that lack sufficient hydrological monitoring infrastructures on the ground. PMID- 26813801 TI - Effects of Repeated Annual Inactivated Influenza Vaccination among Healthcare Personnel on Serum Hemagglutinin Inhibition Antibody Response to A/Perth/16/2009 (H3N2)-like virus during 2010-11. AB - BACKGROUND: Recently, lower estimates of influenza vaccine effectiveness (VE) against A(H3N2) virus illness among those vaccinated during the previous season or multiple seasons have been reported; however, it is unclear whether these effects are due to differences in immunogenicity. METHODS: We performed hemagglutination inhibition antibody (HI) assays on serum collected at preseason, ~ 30 days post-vaccination, and postseason from a prospective cohort of healthcare personnel (HCP). Eligible participants had medical and vaccination records for at least four years (since July, 2006), including 578 HCP who received 2010-11 trivalent inactivated influenza vaccine [IIV3, containing A/Perth/16/2009-like A(H3N2)] and 209 HCP who declined vaccination. Estimates of the percentage with high titers (>= 40 and>100) and geometric mean fold change ratios (GMRs) to A/Perth/16/2009-like virus by number of prior vaccinations were adjusted for age, sex, race, education, household size, hospital care responsibilities, and study site. RESULTS: Post-vaccination GMRs were inversely associated with the number of prior vaccinations, increasing from 2.3 among those with 4 prior vaccinations to 6.2 among HCP with zero prior vaccinations (F[4,567]=9.97, p<.0005). Thirty-two percent of HCP with 1 prior vaccination achieved titers >100 compared to only 11% of HCP with 4 prior vaccinations (adjusted odds ratio=6.8, 95% CI=3.1 - 15.3). CONCLUSION: Our findings point to an exposure-response association between repeated IIV3 vaccination and HI for A(H3N2) and are consistent with recent VE observations. Ultimately, better vaccines and vaccine strategies may be needed in order to optimize immunogenicity and VE for HCP and other repeated vaccinees. PMID- 26813802 TI - The pharmacokinetics of DPH after the administration of a single intravenous or intramuscular dose in healthy dogs. AB - The objective of this study was to determine the pharmacokinetics of diphenhydramine (DPH) in healthy dogs following a single i.v. or i.m. dose. Dogs were randomly allocated in two treatment groups and received DPH at 1 mg/kg, i.v., or 2 mg/kg, i.m. Blood samples were collected serially over 24 h. Plasma concentrations of DPH were determined by high-performance liquid chromatography, and noncompartmental pharmacokinetic analysis was performed with the commercially available software. Cardio-respiratory parameters, rectal temperature and effects on behaviour, such as sedation or excitement, were recorded. Diphenhydramine Clarea , Vdarea and T1/2 were 20.7 +/- 2.9 mL/kg/min, 7.6 +/- 0.7 L/kg and 4.2 +/ 0.5 h for the i.v. route, respectively, and Clarea /F, Vdarea /F and T1/2 20.8 +/- 2.7 mL/kg/min, 12.3 +/- 1.2 L/kg and 6.8 +/- 0.7 h for the i.m. route, respectively. Bioavailability was 88% after i.m. administration. No significant differences were found in physiological parameters between groups or within dogs of the same group, and values remained within normal limits. No adverse effects or changes in mental status were observed after the administration of DPH. Both routes of administration resulted in DPH plasma concentrations which exceeded levels considered therapeutic in humans. PMID- 26813803 TI - Integrating resource defence theory with a neural nonapeptide pathway to explain territory-based mating systems. AB - The ultimate-level factors that drive the evolution of mating systems have been well studied, but an evolutionarily conserved neural mechanism involved in shaping behaviour and social organization across species has remained elusive. Here, we review studies that have investigated the role of neural arginine vasopressin (AVP), vasotocin (AVT), and their receptor V1a in mediating variation in territorial behaviour. First, we discuss how aggression and territoriality are a function of population density in an inverted-U relationship according to resource defence theory, and how territoriality influences some mating systems. Next, we find that neural AVP, AVT, and V1a expression, especially in one particular neural circuit involving the lateral septum of the forebrain, are associated with territorial behaviour in males of diverse species, most likely due to their role in enhancing social cognition. Then we review studies that examined multiple species and find that neural AVP, AVT, and V1a expression is associated with territory size in mammals and fishes. Because territoriality plays an important role in shaping mating systems in many species, we present the idea that neural AVP, AVT, and V1a expression that is selected to mediate territory size may also influence the evolution of different mating systems. Future research that interprets proximate-level neuro-molecular mechanisms in the context of ultimate-level ecological theory may provide deep insight into the brain-behaviour relationships that underlie the diversity of social organization and mating systems seen across the animal kingdom. PMID- 26813804 TI - Demonstration of a near-IR line-referenced electro-optical laser frequency comb for precision radial velocity measurements in astronomy. AB - An important technique for discovering and characterizing planets beyond our solar system relies upon measurement of weak Doppler shifts in the spectra of host stars induced by the influence of orbiting planets. A recent advance has been the introduction of optical frequency combs as frequency references. Frequency combs produce a series of equally spaced reference frequencies and they offer extreme accuracy and spectral grasp that can potentially revolutionize exoplanet detection. Here we demonstrate a laser frequency comb using an alternate comb generation method based on electro-optical modulation, with the comb centre wavelength stabilized to a molecular or atomic reference. In contrast to mode-locked combs, the line spacing is readily resolvable using typical astronomical grating spectrographs. Built using commercial off-the-shelf components, the instrument is relatively simple and reliable. Proof of concept experiments operated at near-infrared wavelengths were carried out at the NASA Infrared Telescope Facility and the Keck-II telescope. PMID- 26813806 TI - Increased Concentrations of Interleukin-33 in the Serum and Cerebrospinal Fluid of Patients with Multiple Sclerosis. AB - OBJECTIVES: Interleukin (IL)-33 is a cytokine with both pro- and anti inflammatory effects involved in the pathogenesis of some inflammatory diseases. The purpose of this investigation was to evaluate the serum and cerebrospinal fluid (CSF) IL-33 concentrations in patients with multiple sclerosis (MS). METHODS: Blood specimens were obtained from 140 patients with MS (46 males and 94 females) with various disease patterns and treatment plans and 140 healthy subjects (47 males and 93 females), who acted as a control group. CSF samples were collected from 20 MS group and 20 sex- and age-matched patients with other neurological diseases of nonautoimmune etiology. The serum and CSF concentrations of IL-33 were measured by the enzyme-linked immunosorbent assay. RESULTS: The serum and CSF IL-33 levels were significantly higher in the MS group compared to the control group (p<0.001 and p<0.050, respectively). The serum IL-33 concentrations were also significantly higher in newly diagnosed (untreated) patients and patients treated with methylprednisolone or with interferon-beta and methylprednisolone compared to the healthy patient group (p<0.007, p<0.002, and p<0.010, respectively). Moreover, the serum IL-33 concentrations in patients with relapsing-remitting (RRMS), primary progressive (PPMS), and secondary progressive (SPMS) forms of the disease were significantly higher than in the healthy control group (p<0.006, p<0.001, and p<0.020, respectively). CONCLUSIONS: Our results showed increased concentrations of IL-33 in patients with MS including both untreated and treated MS patients and patients with the RRMS, SPMS, and PPMS forms. This suggests that IL-33 may be involved in the pathogenesis of all MS forms and treatment with methylprednisolone or both interferon-beta plus methylprednisolone has no influence on IL-33 concentrations. PMID- 26813807 TI - (Un)targeted Scanning of Locks of Hair for Drugs of Abuse by Direct Analysis in Real Time-High-Resolution Mass Spectrometry. AB - Forensic hair evidence can be used to obtain retrospective timelines of drug use by analysis of hair segments. However, this is a laborious and time-consuming process, and mass spectrometric (MS) imaging techniques, which show great potential for single-hair targeted analysis, are less useful due to differences in hair growth rate between individual hairs. As an alternative, a fast untargeted analysis method was developed that uses direct analysis in real time high-resolution mass spectrometry (DART-HRMS) to longitudinally scan intact locks of hair without extensive sample preparation or segmentation. The hair scan method was validated for cocaine against an accredited liquid chromatography/tandem mass spectrometry (LC/MS/MS) method. The detection limit for cocaine in hair was found to comply with the cutoff value of 0.5 ng/mg recommended by the Society of Hair Testing; that is, the DART hair scan method is amenable to forensic cases. Under DART conditions, no significant thermal degradation of cocaine occurred. The standard DART spot size of 5.1 +/- 1.1 mm could be improved to 3.3 +/- 1.0 mm, corresponding to approximately 10 days of hair growth, by using a high spatial resolution exit cone. By use of data dependent product ion scans, multiple drugs of abuse could be detected in a single drug user hair scan with confirmation of identity by both exact mass and MS/HRMS fragmentation patterns. Furthermore, full-scan high-resolution data were retrospectively interrogated versus a list of more than 100 compounds and revealed additional hits and temporal profiles in good correlation with reported drug use. PMID- 26813805 TI - Genitourinary mast cells and survival. AB - Mast cells (MCs) are ubiquitous in the body, but they have historically been associated with allergies, and most recently with regulation of immunity and inflammation. However, it remains a puzzle why so many MCs are located in the diencephalon, which regulates emotions and in the genitourinary tract, including the bladder, prostate, penis, vagina and uterus that hardly ever get allergic reactions. A number of papers have reported that MCs have estrogen, gonadotropin and corticotropin-releasing hormone (CRH) receptors. Moreover, animal experiments have shown that diencephalic MCs increase in number during courting in doves. We had reported that allergic stimulation of nasal MCs leads to hypothalamic pituitary adrenal (HPA) activation. Interestingly, anecdotal information indicates that female patients with mastocytosis or mast cell activation syndrome may have increased libido. Preliminary evidence also suggests that MCs may have olfactory receptors. MCs may, therefore, have been retained phylogenetically not only to "smell danger", but to promote survival and procreation. PMID- 26813808 TI - The lonely doctors. PMID- 26813809 TI - Screening for Mycoplasma genitalium infection? PMID- 26813810 TI - [Re: Chronic fatigue syndrome/myalgic encephalo-myelitis--pathophysiology, diagnosis and treatment]. PMID- 26813811 TI - [Re: Cumulative summation in monitoring postoperative wound infections]. PMID- 26813812 TI - [Re: Circumcision of boys]. PMID- 26813813 TI - [The first liver transplantation in Norway and the way there]. PMID- 26813814 TI - [Oral treatment of vitamin B12 deficiency]. PMID- 26813815 TI - [Not Available]. PMID- 26813816 TI - Prevalence of M. genitalium and U. urealyticum in urine tested for C. trachomatis. AB - BACKGROUND: Mycoplasma genitalium and Ureaplasma urealyticum cause sexually transmitted infections. While M. genitalium is an established aetiological agent, U. urealyticum is still controversial as a pathogen. Testing for these microbes is not yet widely available in Norway, and knowledge of their prevalence is limited. In this study we have investigated the prevalence of M. genitalium and U. urealyticum in a heterogeneous population from Vestfold and Telemark. MATERIAL AND METHOD: Urine samples (n = 4,665) received by the laboratory for testing for Chlamydia trachomatis in the period from February 2011 to January 2012 were subsequently tested for M. genitalium and U. urealyticum. Samples were analysed using an in-house PCR protocol. RESULTS: The prevalence of C. trachomatis, M. genitalium and U. urealyticum was 11.9%, 3.6% and 17.9% respectively. M. genitalium was found most frequently in women aged 20-24 years (5.1%), while the proportion of samples positive for U. urealyticum was greatest in persons aged 15 24 years (22.8%). INTERPRETATION: M. genitalium was highly prevalent in urine samples submitted for C. trachomatis testing. M. genitalium testing was requested for only a minority of the samples analysed, suggesting limited knowledge of this microbe. U. urealyticum was the most predominant microbe in the study, which may indicate that it is largely non-pathogenic. PMID- 26813817 TI - [Primary ciliary dyskinesia]. AB - Primary ciliary dyskinesia (PCD) is a rare disease, but causes symptoms that resemble far more common respiratory diseases. Late diagnosis is common, when damage to the respiratory system has already occurred. This article aims to elucidate the condition and the diagnostic methods available. The article is based on literature searches in PubMed and the author's own experience of patient treatment and clinical research. PMID- 26813818 TI - [Sudden unexpected death in epilepsy (SUDEP)]. AB - Sudden unexpected death is the most frequent cause of seizure-related death in cases of epilepsy. Those primarily affected are young adults with a long disease duration and regular seizures. The deaths are often related to a nocturnal generalised tonic-clonic seizure attack. In Norway around 30 persons are thought to be affected each year. Optimisation of epilepsy treatment will probably prevent some of these deaths. PMID- 26813819 TI - [Air embolism caused by intraosseous needle?]. PMID- 26813820 TI - [A man in his 60s with acute back pain and kidney failure]. PMID- 26813821 TI - [Mobility, semantics and acute neurology]. PMID- 26813822 TI - [Not Available]. PMID- 26813824 TI - [Not Available]. PMID- 26813825 TI - [An academic year in primary health care--a travelogue from Australia]. PMID- 26813826 TI - [Not Available]. PMID- 26813827 TI - [Not Available]. PMID- 26813828 TI - [Not Available]. PMID- 26813829 TI - [Not Available]. PMID- 26813830 TI - [Not Available]. PMID- 26813831 TI - [Attach importance to the planning and implementation of endovascular repair for ascending aorta dissection]. AB - Since 2000 Dorros et al. reported the first case of type A aortic dissection (TAAD) treated with an endovascular repair, surgeons explored a novel treatment option for TAAD gradually. The application of endovascular repair for TAAD highlights some points below which should pay attention to because of the special anatomic location and morphological characteristics of ascending aorta: (1) customized treatment strategy based on the characteristics of patients; (2) pre operation evaluation; (3) selection of the stent and delivery system; (4) selection of the access sites; (5) preservation of the coronary artery flow, aortic valve function and perfusion of the branch vessels; (6) accurate location of stent-graft; (7) mid-term and long-term follow-up. In a word, it's helpful to avoid misunderstanding in treatment and improve the safety of operation by grasping the indication and the technical points and making the customized treatment strategy based on the characteristics of patients. PMID- 26813832 TI - [Endovascular treatment of aortic lesions involving branch vessels with multi layer bare stents]. AB - Aortic lesions involving branch vessels have always been a great challenge for vascular surgeons. Endovascular repair are growing to take place of traditional open repair for less invasion and lower complication rates. Despite rapid developments in endovascular instruments have been achieved in the last decade, and endovascular techniques such as fenestration stents have been applied in the treatment of aortic lesions involving branch vessels. However, endovascular repairing aortic lesions involving branch vessels remains being restricted by rigorous indication selection as well as requirements of advanced experiences and sophisticated skills. Recently, several studies about treating aortic lesion involving branch vessels with multi-layer bare stents have been reported, the primary results were encouraging and brought new visions for the management of such disease. More approving clinical evidences about the safety and efficacy of multi-layer stents are anticipated. PMID- 26813833 TI - [Clinical practice and thinking on chimney technique for endovascular aortic repair]. AB - Chimney technique is an assistive technology of endovascular aortic repair, which is used to reconstruct the vital branch vessel invaded by aortic pathology. In chimney technique, most of the commercial aortic stent-graft can be used, and covered branch stent-graft is recommended to decrease the risk of type I a endoleak. The suggested oversizing for aortic stent-graft and branch stent-graft is 15% and 5% respectively, and the length of overlapping between stent-grafts should be more than 2 cm. Type I a endoleak is the main concentration, appropriated oversizing and overlapping are important precautions theoretically. Anticoagulation therapy post-operation is crucial in preventing restenosis of the chimney stent-graft. PMID- 26813834 TI - [Endovascular aortic repair of infrarenal abdominal aortic aneurysm: a 10-year single center outcomes]. AB - OBJECTIVE: To evaluate the outcome after endovascular aortic repair (EVAR) of abdominal aortic aneurysms (AAA) in single center. METHODS: A total of 711 AAA patients treated by EVAR in Department of Vascular Surgery, People's Liberation Army General Hospital and met the inclusion criteria from January 2004 to June 2014 were followed-up and analyzed. There were 612 male and 99 female patients, with a mean age of (69+/-13) years in this study group. The primary outcome of the study was all-cause mortality, secondary outcome included procedural data, intervention-related morbidity and secondary therapeutic procedures. The endpoint was death. Kaplan-Meier survival analysis were used to analyze long-term survival and cumulative probability of intervention related morbidity. Cox proportional hazards regression was used to analyze factors influenced the survival. Multivariable analysis were adjusted for covariates. RESULTS: There were 74.8% of total patients followed up. The longest follow-up period was 10.4 years (mean 3.8 years). For the primary outcome of all-cause mortality, 140 deaths occurred. Intervention related morbidity was 9.3%, secondary therapeutic procedures was 5.3%.The Kaplan-Meier survival curve showed that cumulative survival is 78% (95% CI: 74% to 82%) in 5 years, 67% (95% CI: 61% to 74%) in 10 years and the cumulative probability of intervention related morbidity is 10.5% (95% CI: 7.3% to 13.7%) in 5 years, 19.3% (95% CI: 11.9% to 26.0%) in 10 years. Cox proportional hazards regression showed that age>75 years, American Society of Anesthesiologists classification III or IV, smoking, diabetes significantly increase the risk of long-term all-cause mortality, while hypertension significantly decreases the risk. CONCLUSIONS: Long-term outcome after EVAR of AAA in the study is similar to those advanced studies.The management of risk factors would improve the prognosis of these patients. PMID- 26813835 TI - [Clinical analysis of hybrid treatment for extensive aortic disease]. AB - OBJECTIVE: To evaluate the effect of extensive aortic diseases (EAD) after hybrid repair with supra-arch branches or visceral arterial debranching and endovascular repair. METHODS: A total of 24 EAD patients (19 male and 5 female) underwent hybrid repair in Department of Vascular Surgery, Zhongshan Hospital, Fudan University between March 2005 and April 2015. The clinical data was analyzed retrospectively. The mean age was (49+/-12) years (from 29 to 69 years). The high risk candidates for open surgery were enrolled in the study. The patients, including 14 cases with thoracic aortic aneurysms and 10 cases with aortic dissection, were treated by one or two stages. Post-operative follow-up with CT angiography was performed at 3, 6 and 12 months and then annually thereafter. RESULTS: A total of 74 branches, including 63 with visceral arteries and 11 with supra-arch arteries, were recanalized. Nine patients were treated in two-stage hybrid procedure and fifteen were repaired by one stage. The perioperative mortality was 12.5% (3/24), whereas the aneurysm-related mortality was 8.3% (2/24). The 30-day patency of the grafts was 95.9% (71/74). There was no endoleak, paralysis, and intestinal ischemia at 30 days post-hybrid procedures. Four cases (16.6%) suffered acute renal dysfunction. During the follow-up (3 to 123 months), there were two deaths and one endoleak (type Ia and III) which emerged at 4 months post-procedure. The 1-year and 3-year survival rates were 81.7% and 73.5%, respectively. CONCLUSIONS: Hybrid treatment is safe and effective for complex EAD patients in the midterm follow-up. It is especially suitable for the high-risk patients with comorbidities, re-intervention, or little tolerance to open surgery repair. PMID- 26813836 TI - [Outcomes of endovascular repairing aortic arch disease hybrid with supra-arch debranching procedures]. AB - OBJECTIVE: To summarize the experience of endovascular repairing aortic arch disease hybrid with supra-arch debranching procedures. METHODS: It was a retrospective study. From January 2002 to December 2014, 42 high risk patients with aortic arch disease were treated by supra-arch debranching hybrid with subsequent endovascular repair in the First Affiliated Hospital of Sun Yat-sen University. There were 39 male and 3 female patients with a mean age of (53+/-13) years (ranging from 34 to 80 years). Of the 42 patients, 7 were thoracic aortic aneurysm, 20 were Stanford type B aortic dissection and 15 were Stanford type A aortic dissection. After the supra-aortic debranching technique, simultaneous (n=16) or staged (n=26, mean interval (7+/-3) days) endovascular repair were performed. Fisher exact test was used to compare the in-hospital mortality of ascending aorta based debranching and non-ascending aorta based debranching. RESULTS: Technical success rate was 81.0% (34/42). The overall 30-day complication rate was 31.0% (13/42), including 3 cerebral stroke (7.1%), 8 endoleak (19.0%, including 6 type I endoleak and 2 type II endoleak), 1 circulatory failure, 1 aorto-tracheal fistula. The 30-day mortality was 9.5% (4/42), 2 died of cerebral stroke, 1 died of circulatory failure, 1 died of aorto tracheal fistula. The in-hospital mortality of ascending aorta based debranching group was obviously higher than that of the non-ascending aorta based debranching group (4/16 vs. 0, P=0.02). The median time of follow-up was 64.8 (2 to 156.9) months. CT scanning was performed at 1, 3 months after surgery and annually thereafter. The overall survival rate was 76.6%. During the follow-up period, there was 4 deaths, and 2 of them were aortic artery related (5.3%). There were 4 de novo complications during the follow-up period, 1 stroke attributed to bypass occlusion was cured by medical treatment, 2 pseudoaneurysm was successfully treated with open surgery, 1 stent-graft induced new distal entry tear was successfully treated with a tapered stent-graft, there was no new endoleak during follow up period, 3 type I endoleak disappeared spontaneously, and 1 type II endoleak disappeared after secondary intervention. CONCLUSIONS: Endovascular repair of aortic arch disease hybrid with supra-arch debranching procedure is low invasive with favorable long-term outcomes. It is suitable for high risk patients of poor general condition with little tolerance to aortic arch replacement. The in-hospital mortality is higher in the ascending aorta based debranching group than in the non-ascending aorta based debranching group. Stroke is a critical fatal complication and should be attached attention. PMID- 26813837 TI - [Operation experience of atypical ruptured abdominal aortic aneurysm]. AB - OBJECTIVE: To evaluate and report surgical management and experience of atypical ruptured abdominal aortic aneurysm (RAAA). METHODS: Clinical data of 52 RAAA patients from May 2002 to February 2015 were retrospectively collected and analyzed. Thirty-three cases were included into this study based on atypical clinical presentation and etiology, including 6 infected RAAA, 5 inflammatory RAAA, 1 traumatic aortic rupture, 6 tuberculotic RAAA, 2 aoritc-vena cava fistula, 3 intestinal fistula and 5 spine erosion cases. Two of them refused operation during preparation, 19 of them received emergency open repair and 13 of them received endovascular aortic repair (EVAR) with 1 case converted to open surgery. RESULTS: The systolic blood pressure of atypical RAAA before operation was (88+/-16) mmHg (1 mmHg=0.133 kPa), duration time from admission to diagnosis making was (17+/-10) hours. Perioperative death occurred in 1 patient because of hemorrhagic shock induced acidosis. During follow-up for 3 to 72 months, no operation related complications occured, such as artificial graft infection. CONCLUSIONS: Emergent operation including open surgery and EVAR is crucial for RAAA treatment. Early diagnosis, excellent operative techniques and comprehensive perioperative management are measures conducive to reduce the mortality rate of RAAA. PMID- 26813838 TI - [The risk factors of splenic arterial steal syndrome after orthotopic liver transplantation]. AB - OBJECTIVE: To discuss the risk factors of splenic arterial steal syndrome (SASS) after orthotopic liver transplantation. METHODS: Twenty-four cases who confirmed SASS after liver transplantation in Tianjin First Central Hospital between June 2005 and June 2013 were analyzed retrospectively. Another 96 cases were selected randomly from those patients of the same time with no complication of SASS patients postoperatively as control group. Clinical data of two groups including diameter of splenic artery and hepatic artery preoperatively, weight of graft, weight of recipients, cold/warm ischemia time, an hepatic period and operation time and so on were collected. Others including hepatic artery peak systolic velocity (PSV), end diastolic velocity (EDV), blood flow resistance index and portal vein average velocity (PVF) on the first day after liver transplantation, the day before diagnosis, the day when diagnosed, the 1, 3, 7 days after treatment in SASS group and on 1, 3, 7, 9, 11, 14 days after liver transplantation in control group. Statistical analysis were made between two groups. RESULTS: The splenic artery/hepatic artery ratio preoperatively and weight of donor liver,and the GRWR in SASS group and control group were 1.26 and 1.00, 1 032 g and 1 075 g, (1.40+/-0.30)% and (1.82+/-0.21)% respectively, with significantly statistical differences (Z=-6.40, Z=-2.22, t=-6.50; all P<0.05). The warm ischemia time, the cold ischemia time, the anhepatic period and operation time in SASS group and control group were 3.5 minutes and 4.0 minutes, 10.25 hours and 10.10 hours, 43 minutes and 45 minutes, 8.7 hours and 8.7 hours, with no significantly statistical differences (all P>0.05). RI of hepatic went up gradually in the early time after transplantation while dropped obviously when spleen artery spring coils embolization was received (P<0.01) and trended to stable two weeks later. CONCLUSIONS: Splenic artery/hepatic artery ratio and GRWR are the positive and negative risk factors respectively for SASS. The gradual rising of hepatic RI in the early time after transplantation may be the warning signal SASS and spleen artery spring coils embolization is the effective strategy for SASS after liver transplantation. PMID- 26813839 TI - [Three-dimensional finite-element study on anterior transpedicular screw fixation system of the subaxial cervical spine]. AB - OBJECTIVE: To evaluate the biomechanical effects of the anterior cervical transpedicular-screw system (ACTPS), compared to the anterior cervical screw plate system (ACLP), in the subaxial cervical spine after 2-level corpectomy. METHODS: A verified intact finite element subaxial cervical (C3-C7) model was established and analyzed by Mimics 10.0, Rapidform XOR3, Hypermesh 10.0, CATIA5V19, ANSYS 14.0 softwares based on the CT data (C1-T1) was collected from a 28 years old male volunteer. The axial force of 75 N and moment couple of 1N.m was loaded on the upper surface of C3, which made the model movement in flexion extension, lateral bending, rotating direction, respectively. Then, recorded the range of motion, and compared the results with the in vitro biomechanical experimental data to verify the effectiveness of the model. The ACTPS model and the ACLP model were analyzed using the finite element method. The range of motion at the operation segments (C4-C7), the range of motion at the adjacent segment (C3-C4) and stress distribution under flexion, extension, lateral bending, and axial rotation were calculated, and compared the range of motion with intact model. RESULTS: There were 85,832 elements and 23,612 nodes in the intact model of subaxial cervical spine (C3-C7) in this experiment,and the range of motion of intact model validated with the reported cadaveric experimental data. In ACTPS group the stress was been well-distributed, but the stress concentrated on the interface between screw and the titanium plate in ACLP group. There were obvious differences of the maximum stress value between the two groups. The range of motion of fixed segments in ACTPS group was smaller than ACLP group, however adjacent segment range of motion showed no significant difference. Compared with the intact group, the range of motion in flexion extension, lateral flexion, rotation direction was decreased respectively about 25 degrees , 20 degrees and 8 degrees , the range of motion at adjacent segment (C3-C4) was correspondingly compensated about 0.3 degrees , 3 degrees and 0.1 degrees . CONCLUSIONS: ACTPS is better than ACLP in terms of biomechanical properties. It offers rigid stability, and may be more suitable for reconstruction stability of 2-level and more than 2 levels corpectomy in the subaxial cervical spine. Meanwhile, the risk of fracture of ACTPS system is lower than that of the ACLP system. PMID- 26813840 TI - [Clinical outcomes of laparoscopic radical prostatectomy for high risk prostate cancer]. AB - OBJECTIVE: To study the technique and clinical outcomes of laparoscopic radical prostatectomy for high risk prostate cancer. METHODS: A total of 65 patients with high risk prostate cancer were treated with surgery in the First Affiliated Hospital of Nanjing Medical University from January 2011 to June 2013. The mean age was 67 years (range 45-75 years). The mean preoperative prostate specific antigen (PSA) level was 26.7 ug/L (range 11.2-65.5 ug/L). The transrectal biopsy revealed Gleason score of 3+3 in 4 patients, Gleason 3+4 in 27 patients, Gleason 4+3 in 11 patients, Gleason 4+4 in 21 patients and Gleason 4+5 in 2 patients. The bone metastasis was excluded by scintigraphy examination. The surgical procedures were performed through transperitoneal approach. Extended pelvic lymph nodes dissection was performed after the removal of the prostate. Adjuvant radiotherapy or hormonal therapy was administrated according to the pathological results. Serum PSA was detected every 1 to 2 month and urinary continence was evaluated every 3 month in the first year, and then serum PSA was detected every 2 to 3 month. RESULTS: The mean operative time was (134+/-21) minutes and the median blood loss was (300+/-146) ml. Bladder neck reconstruction was performed in 15 cases. The drainage was removed on postoperative day 4 and the catheter was removed on day 7. Pathologic results demonstrated pT2 in 25 patients, pT3a in 28 patients, pT3b in 9 patients and pT4 in 3 patients. Positive surgical margin was presented in 15 patients. A median of 19 lymph nodes (range 11-24 nodes) were retrieved during lymphadenectomy and 11 patients had lymph nodes metastasis with a total of 19 positive nodes. Forty-three patients recovered continence after the removal of catheter. Eleven patients received adjuvant hormonal therapy and 19 patients received adjuvant radiation therapy. With the median of 20 months follow up (range 12-30 months), 5 patients got biochemical recurrence. CONCLUSIONS: Laparoscopic radical prostatectomy with extended lymph nodes dissection for high risk prostate cancer is safe and technical feasible. It provides accurate information on tumor stage and grade. It is an important component of multimodality for the treatment of high risk prostate cancer. PMID- 26813841 TI - [Ring suture technique for renorrhaphy during partial nephrectomy in the management of renal hilar cancer]. AB - OBJECTIVE: To evaluate the safety and efficacy of "ring suture technique" during partial nephrectomy in the management of renal cell cancer located in renal hilar. METHODS: The data of 31 patients with renal cell cancer located in renal hilar who underwent partial nephrectomy from January 2009 to January 2014 in Peking University First Hospital were collected. Of the 31 patients, 21 were male, 10 were female ranging from 48 to 75 years (average age of (58+/-13) years). "Ring suture technique" was adopted in all the operation which were performed following the same steps: a ureteral catheter was placed into ipsilateral ureter pre-operatively; renal artery was clamped first and after 30 s renal vein was also clamped; tumor was resected from kidney; the edge of renal parenchyma was sutured continuously; methylthioninium Chloride solution was injected into pelvis retrograde through the ureteral catheter, and the collecting system was repaired if needed; remove renal vein clamp and then the renal artery, repair any injury of the vascular when necessary. The renal ischemic time, blood loss and postoperative complications were analyzed retrospectively. RESULTS: Retroperitoneal laparoscopic surgery and laparotomy were performed in 14 patients and 17 patients each. Average maximum diameter of tumor was (3.3+/-1.2) cm, and median R.E.N.A.L.nephrometry score was 8 (7-11). Average ischemic time was (24+/ 8) minutes (18.4-37.5 minutes). Median blood loss during operation was 130 ml (90 350 ml), average blood loss was (125+/-45) ml, and there was no uncontrollable massive bleeding. Radical nephrectomy was adopted in 1 case due to tumor embolus in branch of renal vein. All patients had good recovery after surgery without complications such as hemorrhage, urine leakage or renal atrophy during the first 3 months after surgery. CONCLUSION: Ring suture technique is a safe and effective method in the management of renal hilar cancer during partial nephrectomy. PMID- 26813842 TI - [Analysis of clinical features of retroperitoneal bronchogenic cyst]. AB - OBJECTIVE: To analyze the clinical features of retroperitoneal bronchogenic cyst. METHODS: The clinical data of 6 cases with retroperitoneal brochogenic cyst treated in Peking Union Medical College Hospital from April 1996 to October 2014 were retrospectively analyzed. The clinical manifestation, diagnosis, treatment and prognosis were analyzed. RESULTS: Of the patients, 1 was male and 5 were female aging from 31 to 50 years with a mean age of 38.3 years. Three cases were diagnosed from physical examination, 2 cases from upper abdominal pain and 1 case from left flank pain. The cysts located in the left adrenal region, between the liver and the pancreas, and anterior aspect of the tail of the pancreas were seen in 4 cases, 1 case and 1 case, respectively. The major diameter was from 5 cm to 13 cm, and the mean major diameter was 7 cm. Ultrasonography and CT scan could reveal cystic, cystic-solid or solid masses. Color doppler flow imaging showed no obvious blood flow, and contrast-enhanced CT scans showed no enhancement or no obvious enhancement. Six cases were all misdiagnosed preoperatively. They all underwent operations via retroperitoneal laparoscopic resection for 3 cases, laparotomy for 2 cases and open flank resection for 1 case respectively. The pathological diagnoses were all bronchogenic cysts. Three symptomatic patients became asymptomatic after operations. Five patients had been followed up. During the follow-up of 2 months to 15 years, no recurrence had been found with CT scan. CONCLUSIONS: Retroperitoneal bronchogenic cyst is rare and easily misdiagnosed. It should be considered in the differential diagnosis of a retroperitoneal mass. Most cysts are positioned in the left adrenal region and adjacent regions. Some cysts demonstrate soft tissue characteristics in image. After surgical removal, the patients have a good prognosis. PMID- 26813843 TI - [Magnetic resonance three dimensional sampling perfection with application optimized contrasts using different flip angle evolution sequence for obstructive hydrocephalus: impact on diagnosis and surgical strategy modification]. AB - OBJECTIVE: To investigate the value of magnetic resonance three dimensional sampling perfection with application optimized contrasts using different flip angle evolution (3D-SPACE) sequences in diagnosis and surgical strategy modification for obstructive hydrocephalus. METHODS: From March 2013 to July 2014, there were 152 cases admitted in People's Liberation Army General Hospital suffered from hydrocephalus, including 88 male patients and 64 female patients aging from 8 months to 79 years. All patients were performed magnetic resonance T2WI and 3D-SPACE sequence scanning before operation. Surgical strategy was made after evaluation of 3D-SPACE sequence. Non-communicating hydrocephalus was treated with endoscopic third ventriculostomy (ETV) and communicating hydrocephalus was treated with ventriculo-peritoneal shunt. According to MR images of direct observation to site of obstruction to determine the detection rate. MRI 3D-SPACE and cranial CT examination were performed in regular follow-up studies. RESULTS: The relevance ratio of 3D-SPACE for the diagnosis of non communicating hydrocephalus was 98.3% (114/116), while the relevance ratio of conventional T2-weighted MRI was 72.4% (84/116). Among the 152 patients, there were 36 cases with cerebral aqueduct film obstruction, 22 cases with space occupying lesions in pineal region, posterior part of the third ventricle, or space-occupying lesions in quadrigeminal bodies area, 10 cases with Dandy-Walker symptom, 18 cases with cyst of the anterior pool of the bridge, 16 cases with cysticercosis, 4 cases with cyst of lateral ventricle, 2 cases with cyst of fourth ventricle, 2 cases with space-occupying lesion in foramen ofmonro, 2 cases with foramen ofmonro atresia, 4 cases with craniopharyngioma, 36 cases with communicating hydrocephalus. There were 112 hydrocephalus cases (73.7%) were treated with ETV, without shunt catheter insertion in follow-up study from 1 to 18 months (average (14+/-9) months). CONCLUSIONS: For obstructive hydrocephalus, MRI 3D-SPACE sequence image has high diagnostic yield rate for providing more detailed anatomical information than conventional MRI. Hence, the advanced imaging methods are helpful for surgical treatment strategy decision making. PMID- 26813844 TI - [Strategy of visceral arteries reconstruction during the endovascular therapy of the aortic dilated disease]. AB - Endovascular repair has gradually become the mainstream treatment of aortic dilatation disease. However, endovascular therapy requires sufficient landing zone both in the proximal and distal region of aortic lesion. A large proportion of aortic dilatation lesion was excluded from traditional endovascular therapy due to the visceral artery involvement or being too close to the orifice of viceral artery. Recently, with the adoption of chimney technique, sandwich technique and hybrid technique and the advent of fenestrated and branched stent graft expand the application of endovascular repair technology, rendering these specific type of aortic disease gradually got the chance to endovascular surgery. Different technology has its own characteristics and scope. The surgeons should make their own judgment and selection based on the specific characteristics of lesions, their experience and accessibility to special equipment and other related factors. PMID- 26813845 TI - Randomized Controlled Pilot Trial of Behavioral Insomnia Treatment for Chronic Migraine With Comorbid Insomnia. AB - BACKGROUND: Migraine frequently co-occurs with and is triggered by sleep disturbance, particularly insomnia, and the large majority of patients with chronic migraine (CM) have comorbid insomnia. Limited evidence suggests that behavioral regulation of sleep may reduce migraine frequency, but studies to date have not assessed the viability of stimulus control and sleep restriction interventions or included objective measurement of sleep parameters. The aim of this study, thus, was to pilot-test the efficacy of a brief behavioral insomnia intervention for adults with CM and comorbid insomnia; headache diaries and actigraphy were included to assess outcomes throughout the trial. METHODS: This randomized parallel-arm pilot trial recruited adults with both CM and comorbid insomnia. Participants were randomly assigned to three 30-minute biweekly sessions of cognitive-behavioral therapy for insomnia (CBTi) or control treatment. Participants were blinded to treatment and control conditions to control for outcome expectations. Each treatment condition involved training in and daily practice in 5 instructions/skills. The CBTi group learned and practiced skills pertaining to stimulus control and sleep restriction. The control intervention was the same as used by Calhoun and Ford (2007) and involved training in and daily practice of skills pertaining to keeping a consistent food/liquid intake, range of motion exercises, and acupressure. Participants provided outcome data via daily headache diaries, actigraphy, and self-report measures. The primary outcome was reduction in headache frequency at 2 weeks post treatment and 6-week follow-up; secondary outcomes included other headache parameters, objective actigraphic and subjective changes in sleep, and treatment effect sizes and perceived credibility. Generalized estimating equations with a binomial logit link and inverse probability weights were used to assess the primary outcome among the intent-to-treat sample, and repeated measures generalized linear models were used to assess changes in secondary outcomes after controlling for baseline values. RESULTS: The intent-to-treat analyses included 31 adults (M age = 30.8 [12.9] years; 90.3% female; 80.6% white) with CM and comorbid insomnia. Both interventions yielded reductions in headache frequency at post-treatment (26.9% reduction for CBTi vs. 36.2% for control) and follow-up (48.9% for CBTi vs. 25.0% for control). At follow-up the odds of experiencing headache were 60% lower for CBTi than for control treatment, indicative of a large effect size that did not reach statistical significance after Bonferroni correction for assessing two primary endpoints (odds ratio: 0.40; 95% CI: 0.17, 0.91; P = .028). CBTi produced significantly larger increases than control treatment in total sleep time and sleep efficiency as quantified by actigraphy, as well as in self-reported insomnia severity. Adherence was high and treatments were perceived as credible without differences between groups, but the control group experienced a higher rate of dropouts. No adverse events were reported. CONCLUSIONS: Behavioral treatment of comorbid insomnia in individuals with CM produced large reductions in headache frequency, though some improvement in headache occurred with a behavioral intervention not focused on modifying sleep. Among the CBTi group only, both headache frequency and sleep parameters continued to improve after treatment, suggesting the presence of enduring effects over time. Directly treating insomnia using components of stimulus control and sleep restriction holds promise for reducing comorbid migraine. Development of and comparison to a truly inert pseudotherapy control presents unique challenges that future studies should address. PMID- 26813846 TI - Demographics, disparities, and outcomes in substernal goiters in the United States. AB - BACKGROUND: Disparities distinguishing patients with substernal goiters from nonsubsternal goiters have not been thoroughly described. METHODS: The National Inpatient Sample database was used to compare patients who underwent substernal thyroidectomy years 2000 to 2010 with those who underwent thyroidectomy for nonsubsternal goiter. RESULTS: A total of 110,889 patients underwent thyroidectomy for goiter (5,525 substernal and 105,364 nonsubsternal). Substernal thyroidectomy patients were older, more likely to be Black or Hispanic and to have Medicare insurance. They had a higher comorbidity index, were more likely to be admitted emergently and to have postoperative complications such as hemorrhage/hematoma, pneumothorax, pulmonary embolism, and hypocalcemia/hypoparathyroidism. Furthermore, substernal thyroidectomy patients had 73% increased odds of death during admission than nonsubsternal thyroidectomy patients. CONCLUSIONS: Substernal goiters present a distinct type of goiter with identifiable patient-level characteristics and an increased risk of postoperative complications and death. Earlier identification and treatment of goiters may allow earlier interventions at a stage when risks are reduced. PMID- 26813847 TI - Exogenous testosterone: a preventable cause of male infertility. AB - MAIN PROBLEM: Testosterone replacement therapy inhibits spermatogenesis, representing a problem for hypogonadal men of reproductive age. METHODS: A literature review of PubMed from 1990-2013. Semen analysis and pregnancy outcomes, time to recovery of spermatogenesis, serum and intratesticular testosterone levels were examined. RESULTS: Exogenous testosterone suppresses intratesticular testosterone production, which is an absolute prerequisite for normal spermatogenesis. Therapies that protect the testis involve human chorionic gonadotropin (hCG) therapy or selective estrogen receptor modulators (SERMs), but may also include low dose hCG with exogenous testosterone. SERMs, such as clomiphene citrate, are effective for maintaining testosterone production and represent a well-tolerated, oral therapy. Routine use of aromatase inhibitors is not recommended based on a lack of long-term data. CONCLUSIONS: Exogenous testosterone supplementation decreases sperm production. Studies of hormonal contraception indicate that most men have a return of normal sperm production within 1 year after discontinuation. Clomiphene citrate is a safe and effective therapy for men who desire to maintain future potential fertility. Although less frequently used in the general population, hCG therapy with or without testosterone supplementation represents an alternative treatment. PMID- 26813848 TI - Optical analysis of RE(3+) (RE = Pr(3) (+) , Er(3) (+) and Nd(3) (+) ):cadmium lead boro tellurite glasses. AB - This article reports on the optical characterization of Pr(3) (+) -, Er(3) (+) - and Nd(3) (+) -doped cadmium lead boro tellurite (CLBT) glasses prepared using the melt quenching method. The visible-near infrared (Vis-NIR) absorption spectra of these glasses were analyzed systematically. On measuring the NIR emission spectra of Er(3) (+) :CLBT glasses, a broad emission band centered at 1536 nm ((4) I13 /2 -> (4) I15 /2 ) was observed, as were three NIR emission bands at 900 nm ((4) F3 /2 -> (4) I9 /2 ), 1069 nm ((4) F3 /2 -> (4) I11 /2 ) and 1338 nm ((4) F3 /2 -> (4) I13 /2 ) from Nd(3) (+) :CLBT glasses and an NIR emission band at 1334 nm ((1) G4 -> (3) H5 ) from Pr(3) (+) :CLBT glasses at an excitation wavelength (lambdaex ) of 514.5 nm (Ar(+) laser). Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26813849 TI - A randomized, blinded, placebo-controlled trial of education and iron supplementation for mitigation of iron deficiency in regular blood donors. AB - BACKGROUND: The historical approach of offering dietary advice to donors with low hemoglobin (Hb) is ineffective for preventing iron deficiency in frequent donors. Alternative approaches to maintaining donor iron status were explored. STUDY DESIGN AND METHODS: Frequent blood donors were randomly assigned into five arms for 2 years of follow-up. Three double-blinded arms provided 60 once-daily pills after each donation (38, 19, or 0 mg of iron). Two single-blinded arms provided iron status (ferritin) or no information letters after each donation. Ferritin, soluble transferrin receptor, and complete blood count were measured at each donation. RESULTS: There were 692 subjects enrolled and 393 completed the study. Subjects in pill groups deenrolled more than those in letter groups (39% vs. 7%). Adverse events occurred equally in subjects receiving iron or placebo pills. Of those completing the study, the prevalence of ferritin of less than 12 or less than 26 ng/mL declined by more than 50% and was statistically indistinguishable in the three intervention groups (19 or 38 mg of iron; iron status letter). Longitudinal analyses of all subjects showed improved iron status in iron pill groups and worsening iron status in control groups (placebo; no information letter). The iron pill groups experienced a net increase of approximately 0.6 g/dL Hb compared to control groups. The iron status letter group had little change in Hb. CONCLUSION: Providing 19 or 38 mg of daily iron or iron status information were effective and mostly equivalent interventions for mitigating iron deficiency in regular donors when compared at the end of the 2-year longitudinal phase of the study. Donors without intervention had worsened iron deficiency with continued donation. PMID- 26813850 TI - Contribution of ionic silver to genotoxic potential of nanosilver in human liver HepG2 and colon Caco2 cells evaluated by the cytokinesis-block micronucleus assay. AB - Extensive human exposure to food- and cosmetics-related consumer products containing nanosilver is of public concern because of the lack of information about their safety. Genotoxicity is an important endpoint for the safety and health hazard assessment of regulated products including nanomaterials. The in vitro cytokinesis-block micronucleus (CBMN) assay is a very useful test for predictive genotoxicity testing. Recently, we have reported the genotoxicity of 20 nm nanosilver in human liver HepG2 and colon Caco2 cells evaluated using the CBMN assay. The objective of our present study was three-fold: (i) to evaluate if HepG2 and Caco2 cells are valuable in vitro models for rapid genotoxicity screening of nanosilver; (ii) to test the hypothesis that the nanoparticle size and cell types are critical determinants of its genotoxicity; and (iii) to determine if ionic silver contributes to the nanosilver genotoxicity. With these objectives in mind, we evaluated the genotoxic potential of 50 nm nanosilver of the same shape, composition, surface charge, obtained from the same commercial source, under the same experimental conditions and the same genotoxic CBMN endpoint used for the previously tested 20 nm silver. The ionic silver (silver acetate) was also evaluated under the same conditions. Results of our study show that up to the concentrations tested in these cell types, the smaller (20 nm) nanosilver induces micronucleus formation in both the cell types but the larger (50 nm) nanosilver and the ionic silver provide a much weaker response compared with controls under the same conditions. PMID- 26813851 TI - The contemporary role of 1 vs. 2-stage repair for proximal hypospadias. AB - This review discusses the most commonly employed techniques in the repair of proximal hypospadias, highlighting the advantages and disadvantages of single versus staged surgical techniques. Hypospadias can have a spectrum of severity with a urethral meatus ranging from the perineum to the glans. Associated abnormalities are commonly found with proximal hypospadias and encompass a large spectrum, including ventral curvature (VC) up to 50 degrees or more, ventral skin deficiency, a flattened glans, penile torsion and penoscrotal transposition. Our contemporary understanding of hypospadiology is comprised of a foundation built by experts who have described a number of techniques and their outcomes, combined with survey data detailing practice patterns. The two largest components of hypospadias repair include repair of VC and urethroplasty. VC greater than 20 degrees is considered clinically relevant to warrant surgical correction. To repair VC, the penis is first degloved-a procedure that may reduce or remove curvature by itself in some cases. Residual curvature is then repaired with dorsal plication techniques, transection of the urethral plate, and/or ventral lengthening techniques. Urethroplasty takes the form of 1- or 2-stage repairs. One-stage options include the tubularized incised urethroplasty (TIP) or various graft or flap-based techniques. Two-stage options also include grafts or flaps, including oral mucosal and preputial skin grafting. One stage repairs are an attractive option in that they may reduce cost, hospital stay, anesthetic risks, and time to the final result. The downside is that these repairs require mastery of multiple techniques may be more complex, and-depending on technique-have higher complication rates. Two-stage repairs are preferred by the majority of surveyed hypospadiologists. The 2-stage repair is versatile and has satisfactory outcomes, but necessitates a second procedure. Given the lack of clear high quality evidence supporting the superiority of one approach over the others, hypospadiologists should develop their own algorithm, which gives them the best outcomes. PMID- 26813852 TI - PEDOT:PSS as multi-functional composite material for enhanced Li-air-battery air electrodes. AB - We propose PEDOT: PSS as a multi-functional composite material for an enhanced Li air-battery air electrode. The PEDOT: PSS layer was coated on the surface of carbon (graphene) using simple method. A electrode containing PEDOT: PSS-coated graphene (PEDOT electrode) could be prepared without binder (such as PVDF) because of high adhesion of PEDOT: PSS. PEDOT electrode presented considerable discharge and charge capacity at all current densities. These results shows that PEDOT: PSS acts as a redox reaction matrix and conducting binder in the air electrode. Moreover, after cycling, the accumulation of reaction products due to side reaction in the electrode was significantly reduced through the use of PEDOT: PSS. This implies that PEDOT: PSS coating layer can suppress the undesirable side reactions between the carbon and electrolyte (and/or Li2O2), which causes enhanced Li-air cell cyclic performance. PMID- 26813854 TI - Surviving Penetrating Brainstem Injury by Bamboo Sticks: Rare Case Reports and a Brief Review of Literature. AB - BACKGROUND AND IMPORTANCE: Chopsticks are common utensils used in many Asian cultures. However, they sometimes can be used as weapons or can cause accidents, particularly in children. Penetrating transorbital/transpharyngeal intracranial injuries with bamboo sticks are peculiar accidents and are relatively rare. Because of their rarity, the management of such injuries is often complex. We discuss 3 cases of penetration of the brainstem by bamboo sticks, 1 case through the foramen magnum, which, to the best of our knowledge, is the first reported case of such an injury. CLINICAL PRESENTATION: The case of a 50-year-old man who was stabbed with a pair of chopsticks in his left eye is presented. The chopsticks passed through the cavernous sinus, and the patient sustained superior orbital fissure syndrome. The other 2 cases were those of a 4-year-old girl having a similar pattern but different mechanism of injury and a 2-year-old boy who sustained transpharyngeal intracranial injury via the foramen magnum. Computed tomography, magnetic resonance imaging, and computed tomographic angiography (CTA) are the key imaging modalities frequently used to determine the course and extent of brain injury. CONCLUSION: Early surgical exploration by a multidisciplinary team approach is essential for attaining a favorable outcome. All cases demonstrated good postoperative recovery and were successfully managed by removing the foreign body through its trajectory. We discuss and briefly review the literature on patterns, complications, and management issues of these less common injuries. PMID- 26813853 TI - A Comparison of Actual and Perceived Sexual Risk Among Older Adults. AB - Sexual risk among older adults (OAs) is prevalent, though little is known about the accuracy of sexual risk perceptions. Thus, the aim was to determine the accuracy of sexual risk perceptions among OAs by examining concordance between self-reported sexual risk behaviors and perceived risk. Data on OAs aged 50 to 92 were collected via Amazon.com's Mechanical Turk. Frequency of sexual risk behaviors (past six months) were reported along with perceived risk, namely, sexually transmitted infection (STI) susceptibility. Accuracy categories (accurate, underestimated, overestimated) were established based on dis/concordance between risk levels (low, moderate, high) and perceived risk (not susceptible, somewhat susceptible, very susceptible). Approximately half of the sample reported engaging in vaginal (49%) and/or oral sex (43%) without a condom in the past six months. However, approximately two-thirds of the sample indicated they were "not susceptible" to STIs. No relationship was found between risk behaviors and risk perceptions, and approximately half (48.1%) of OAs in the sample underestimated their risk. Accuracy was found to decrease as sexual risk level increased, with 93.1% of high-risk OAs underestimating their risk. Several sexual risk behaviors are prevalent among OAs, particularly men. However, perception of risk is often inaccurate and warrants attention. PMID- 26813856 TI - Imaging Surrogates of Infiltration Obtained Via Multiparametric Imaging Pattern Analysis Predict Subsequent Location of Recurrence of Glioblastoma. AB - BACKGROUND: Glioblastoma is an aggressive and highly infiltrative brain cancer. Standard surgical resection is guided by enhancement on postcontrast T1-weighted (T1) magnetic resonance imaging, which is insufficient for delineating surrounding infiltrating tumor. OBJECTIVE: To develop imaging biomarkers that delineate areas of tumor infiltration and predict early recurrence in peritumoral tissue. Such markers would enable intensive, yet targeted, surgery and radiotherapy, thereby potentially delaying recurrence and prolonging survival. METHODS: Preoperative multiparametric magnetic resonance images (T1, T1 gadolinium, T2-weighted, T2-weighted fluid-attenuated inversion recovery, diffusion tensor imaging, and dynamic susceptibility contrast-enhanced magnetic resonance images) from 31 patients were combined using machine learning methods, thereby creating predictive spatial maps of infiltrated peritumoral tissue. Cross validation was used in the retrospective cohort to achieve generalizable biomarkers. Subsequently, the imaging signatures learned from the retrospective study were used in a replication cohort of 34 new patients. Spatial maps representing the likelihood of tumor infiltration and future early recurrence were compared with regions of recurrence on postresection follow-up studies with pathology confirmation. RESULTS: This technique produced predictions of early recurrence with a mean area under the curve of 0.84, sensitivity of 91%, specificity of 93%, and odds ratio estimates of 9.29 (99% confidence interval: 8.95-9.65) for tissue predicted to be heavily infiltrated in the replication study. Regions of tumor recurrence were found to have subtle, yet fairly distinctive multiparametric imaging signatures when analyzed quantitatively by pattern analysis and machine learning. CONCLUSION: Visually imperceptible imaging patterns discovered via multiparametric pattern analysis methods were found to estimate the extent of infiltration and location of future tumor recurrence, paving the way for improved targeted treatment. PMID- 26813857 TI - Pulsatile Dynamics of the Optic Nerve Sheath and Intracranial Pressure: An Exploratory In Vivo Investigation. AB - BACKGROUND: Raised intracranial pressure (ICP) may lead to increased stiffness of the optic nerve sheath (ONS). OBJECTIVE: To develop a method for analyzing ONS dynamics from transorbital ultrasound and investigate a potential difference between patients with raised ICP vs normal ICP. METHODS: We retrospectively analyzed data from 16 patients (<=12 years old) for whom ultrasound image sequences of the ONS had been acquired from both eyes just before invasive measurement of ICP. Eight patients had an ICP >=20 mm Hg. The transverse motion on each side of the ONS was estimated from ultrasound, and Fourier analysis was used to extract the magnitude of the displacement corresponding to the heart rate. By calculating the normalized absolute difference between the displacements on each side of the ONS, a measure of ONS deformation was obtained. This parameter was referred to as the deformability index. According to our hypothesis, because deformability is inversely related to stiffness, we expected this parameter to be lower for ICP >=20 mm Hg compared with ICP <20 mm Hg. The one-sided Mann-Whitney U test was used for statistical comparison. RESULTS: The deformability index was significantly lower in the group with ICP >=20 mm Hg (median value 0.11 vs 0.24; P = .002). CONCLUSION: We present a method for assessment of ONS pulsatile dynamics using transorbital ultrasound imaging. A significant difference was noted between the patient groups, indicating that deformability of the ONS may be relevant as a noninvasive marker of raised ICP. The clinical implications are promising and should be investigated in future clinical studies. ABBREVIATIONS: AUC, area under curveICP, intracranial pressureONS, optic nerve sheathONSD, optic nerve sheath diameterROC, receiver operating characteristic. PMID- 26813858 TI - Anterior Nucleus Deep Brain Stimulation for Refractory Epilepsy: Insights Into Patterns of Seizure Control and Efficacious Target. AB - BACKGROUND: Anterior nucleus (AN) deep brain stimulation (DBS) is a palliative treatment for medically refractory epilepsy. The long-term efficacy and the optimal target localization for AN DBS are not well understood. OBJECTIVE: To analyze the long-term efficacy of AN DBS and its predictors. METHODS: We performed a retrospective review of 16 patients who underwent AN DBS. We selected only patients with reliable seizure frequency data and at least a 1-year follow up. We studied the duration of the seizure reduction after DBS insertion and before stimulation (the insertional effect) and its association with long-term outcome. We modeled the volume of activation using the active contacts, stimulation parameters, and postoperative imaging. The overlap of this volume was plotted in Montreal Neurological Institute 152 space in 7 patients with significant clinical efficacy. RESULTS: Nine patients reported a decrease in seizure frequency immediately after electrode insertion (insertional or microthalamotomy effect). The duration of insertional effect varied from 2 to 4 months. However, 1 patient had a long-term insertional effect of 36 months. Altogether, 11 patients reported >50% decrease in seizure frequency with long term stimulation. The most common pattern of seizure control was immediate and sustained stimulation benefit (n = 8). In patients with long-term stimulation benefit, the efficacious target was localized in the anteroventral AN in close proximity to the mammillothalamic tract. CONCLUSION: AN DBS is efficacious in the control of seizure frequency in selected patients. An insertional effect is commonly observed (56%). The most efficacious site of stimulation appears to be the anteroventral AN. ABBREVIATIONS: AN, anterior nucleusDBS, deep brain stimulationMNI, Montreal Neurological InstituteMRE, medical refractory epilepsyMT, mammillothalamic tractSANTE, Stimulation of the Anterior Nucleus of the Thalamus for EpilepsyVNS, vagal nerve stimulation. PMID- 26813859 TI - Contribution of Lordotic Correction on C5 Palsy Following Cervical Laminectomy and Fusion. AB - BACKGROUND: C5 palsy is a well-reported complication of cervical spine surgery. The implication of sagittal cervical alignment parameters and their changes after surgery on the incidence of C5 palsy remains unclear. OBJECTIVE: We review cervical alignment changes in our cases of C5 palsy after cervical laminectomy and fusion. METHODS: Cases of C5 palsy were retrospectively compared with a control group. Preoperative and postoperative upright plain film radiographs were analyzed in blinded fashion. RESULTS: Spine registry analysis identified 148 patients who underwent cervical laminectomy and fusion by the senior author over 5 years. There were 18 (12%) cases complicated by postoperative C5 palsy. Nine of these 18 patients had prerequisite upright films and were compared with a randomly constructed case control group of 20 patients. There were no statistically significant differences between the 2 groups in age, proportion of males, and preoperative Nurick score. Measures of sagittal alignment did not differ significantly between the 2 groups on preoperative and postoperative imaging. When comparing the amount of alignment change between preoperative and postoperative upright imaging, however, patients with C5 palsy had a statistically higher amount of average C4-C5 Cobb angle change (-2.53 vs 0.78 degrees ; P = .01). Logistic regression analysis demonstrated that lordotic change in both C4-C5 and C2-C7 Cobb angles were associated with development of palsy. CONCLUSION: Lordotic cervical correction, as measured on upright imaging, was statistically larger in patients who had C5 palsy. The role of deformity correction in C5 palsy deserves further study and may inform intraoperative decision making. ABBREVIATION: CLF, cervical laminectomy and fusion. PMID- 26813860 TI - Protective effect of diallyl trisulfide against naphthalene-induced oxidative stress and inflammatory damage in mice. AB - The aim of this study was to investigate the possible protective effects of diallyl trisulfide (DATS) against naphthalene-induced oxidative and inflammatory damage in the livers and lungs of mice. Elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels showed significant hepatic damage after the challenge with 100 mg/kg naphthalene. Hepatic malondialdehyde (MDA) contents and the activity of myeloperoxidase (MPO) increased significantly, accompanying a decrease in the hepatic activity of total superoxide dismutase (SOD) and glutathione (GSH) levels after the naphthalene damage. In addition, the serum levels of nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), and interleukin 8 (IL-8) increased significantly in the groups damaged with naphthalene. The main parameters related to oxidative stress and inflammatory responses in the lungs, including the NO, MPO, and GSH contents, were determined, and the histopathological and immunohistochemical changes in the lung and liver tissues were also observed. In the DATS-treated groups, all of the oxidative and inflammatory damage in the serum, liver, and lung tissues were significantly prevented. PMID- 26813861 TI - Immunomodulatory impression of anti and pro-inflammatory cytokines in relation to humoral immunity in human scabies. AB - The chief manifestations of scabies are mediated through hypersensitivity-like reactions and immune responses which are so far not well understood and remain poorly characterized. The aim of this study is to investigate the role of inflammatory cytokines in relation to humoral immunity in patients with scabies. Serum levels of total IgE, specific IgG, IL-10, IL-6, INF-gamma, and TNF-alpha were investigated in a cross-sectional study including 37 patients with manifestations suggestive of scabies and serologically positive for anti Sarcoptes IgG, in addition to 20 healthy controls. The median value of total IgE was 209 (range, 17-1219 IU/mL), reflecting its wide range within cases. IL-10 showed significant higher levels (287 +/-: 139) in cases than in controls (17.4 +/- 11.32). A positive correlation was reported between total IgE and severity of manifestations (r = 0.429, P <0.005). A significant positive correlation was observed between total IgE and both IgG and IL-6. On the contrary, a negative correlation was recorded between IL-6 and TNF-alpha which makes us suggested anti inflammatory rather than pro-inflammatory effect of IL-6. Moreover, a negative correlation was noticed between the anti-inflammatory cytokine IL-10 and severity of manifestations, specific IgG, total IgE, and INF-gamma. Therefore, the current study theorized a regulatory role of IL-10 in inflammatory responses of scabietic patients suggesting further future analysis of its therapeutic potential. PMID- 26813863 TI - Atomic and electronic aspects of the coloration mechanism of gasochromic Pt/Mo modified V2O5 smart films: an in situ X-ray spectroscopic study. AB - In this work, gasochromic pristine and Mo-modified V2O5 thin films were prepared by the sol-gel spin coating method. Both films exhibit excellent gasochromic coloration. Synchrotron grazing incidence X-ray diffraction reveals that the Mo modified V2O5 thin film is more amorphous than the pristine V2O5 thin film. X-ray absorption spectroscopy (XAS) was utilized to elucidate the modifications of the local electronic and atomic structures that are caused by Mo. In situ soft-XAS and in situ hard-XAS were performed to monitor the effect of the adsorption of dihydrogen on the charge state of vanadium and local atomic rearrangement in the gasochromic thin films. The gasochromic V2O5 film has a significantly pyramid like oxygen-coordinated environment. However, the Mo-modified film exhibits mixed pyramid- and octahedral-like structures. Analytic results indicate that upon gasochromic coloration, adsorption of hydrogen adds electrons to the V 3d t2g orbital, lowering the charge state of vanadium. The films undergo structural modification before the valence is changed. The Mo-modified V2O5 film exhibits faster coloration because the apical V-O bond differs from that in the pristine V2O5 film. This in situ XAS allows real-time monitoring of changes in the element specific local atomic structure during the gasochromic reaction and enables the elucidation of the gasochromic mechanism. PMID- 26813862 TI - Anti-laminin-1 antibodies in serum and follicular fluid of women with Hashimoto's thyroiditis undergoing in vitro fertilization. AB - The aim of this study is to evaluate the presence of anti-laminin-1 antibodies (aLN-1) in sera and follicular fluid (FF) of infertile women affected by Hashimoto's thyroiditis (HT) undergoing in vitro fertilization (IVF) and its impact on oocyte maturation and IVF outcome. aLN-1 were measured by a home-made enzyme linked immunosorbent assay (ELISA) in: (1) sera and FF from 44 infertile women affected by HT (HTIW) with tubal factor or male factor as primary cause of infertility; (2) in sera and FF from 28 infertile women without HT, with tubal factor or male factor as cause of infertility (infertile controls-ICTR); and (3) in sera from 50 fertile women (FW). aLN-1 serum levels were significantly higher in HTIW when compared with both fertile women and ICTR (P <0.001and P <0.01, respectively). Assuming as cutoff the 99th percentile of values obtained in sera of FW, 43.2% of HTIW and 3.6% of ICTR were aLN-1 positive (P = 0.0001). Also aLN 1 detected in FF from HTIW were significantly higher in comparison with those found in FF of ICTR (P = 0.006). In HTIW, metaphase II oocyte count showed inverse correlation with both serum and FF aLN-1 levels (r = 0.34, P = 0.02 and r = 0.33, P = 0.03, respectively). Implantation and pregnancy rates were significantly lower in HTIW (7.9% and 9.1%, respectively) when compared with ICTR (23% and 31.1%, respectively) (P = 0.015 and P = 0.03, respectively). Our results demonstrated for the first time the presence of aLN-1 in a relevant percentage of HTIW and suggest that these auto-antibodies may impair IVF outcome. PMID- 26813864 TI - Matrin3: connecting gene expression with the nuclear matrix. AB - As indicated by its name, Matrin3 was discovered as a component of the nuclear matrix, an insoluble fibrogranular network that structurally organizes the nucleus. Matrin3 possesses both DNA- and RNA-binding domains and, consistent with this, has been shown to function at a number of stages in the life cycle of messenger RNAs. These numerous activities indicate that Matrin3, and indeed the nuclear matrix, do not just provide a structural framework for nuclear activities but also play direct functional roles in these activities. Here, we review the structure, functions, and molecular interactions of Matrin3 and of Matrin3 related proteins, and the pathologies that can arise upon mutation of Matrin3. WIREs RNA 2016, 7:303-315. doi: 10.1002/wrna.1336 For further resources related to this article, please visit the WIREs website. PMID- 26813866 TI - Use of denosumab in a dialysis patient with bone metastases from breast cancer and hepatorenal polycystic disease: a case report. AB - Cancer patients with severe renal dysfunction represent a challenge for the physician. This is the first case report on the use of denosumab in a dialysis patient with bone metastases. We present the clinical case of a 45-year-old woman who had hepatorenal polycystic disease, diagnosed during childhood, and stage IV chronic kidney failure at the time of breast cancer diagnosis. Three years after surgery plus adjuvant hormonal therapy she suffered a further worsening of renal function, requiring dialysis, and very advanced bone metastasis in the hip with severe pain. As pamidronate was the only bone agent available in the center, she received it for 4 months (before a dialysis session), during which time the bone metastases stabilized. In March 2014, the patient switched to denosumab (which had become available in the center), and continued with hormone therapy. Seven months after denosumab initiation, the patient had almost complete pain relief, and the bone metastases exhibited radiological improvement. The tolerability was excellent, without any related adverse event. There were no changes in albumin adjusted serum calcium, serum phosphorus, and intact parathyroid hormone, except for a transient and mild hypocalcemia at 3 months and an increase in intact parathyroid hormone levels, which required adjustment of vitamin D analog dose. Denosumab can be administered to prevent skeletal-related events in patients with bone metastasis from solid tumors and severely impaired renal function, even in those requiring dialysis. In this particular patient, the safety was good. PMID- 26813865 TI - Spontaneous regression of tumour and the role of microbial infection- possibilities for cancer treatment. AB - This review deals with the role of microorganisms in spontaneous regression of a tumour. Spontaneous cancer regression is a phenomenon that has been described for many centuries. One of the most well known methods of inducing spontaneous regression of cancer is the application of Coley's toxin (heat-killed Streptococcus pyogenes and Serratia marcescens), which has been used for the successful treatment of sarcomas, carcinomas, lymphomas, myelomas and melanomas. In clinical practice, the use of Bacillus Calmette-Guerin vaccine for the treatment of superficial urinary bladder cancer is the most common instance of the application of microorganisms for the treatment of cancer. This review provides further information on other tested bacteria--Clostridium spp., Bifidobacterium spp., Lactobacillus spp. and Salmonella spp.--in this field of study. Among new age methods, bactofection, alternative gene therapy, combination bacteriolytic therapy and bacteria-directed enzyme prodrug therapy are some of the potential cancer treatment modalities that use microorganisms. We have also provided information about the interconnection among microorganisms, immune system response, and the possible mechanisms involved in the spontaneous regression of tumours. PMID- 26813867 TI - Climatic irregular staircases: generalized acceleration of global warming. AB - Global warming rates mentioned in the literature are often restricted to a couple of arbitrary periods of time, or of isolated values of the starting year, lacking a global view. In this study, we perform on the contrary an exhaustive parametric analysis of the NASA GISS LOTI data, and also of the HadCRUT4 data. The starting year systematically varies between 1880 and 2002, and the averaging period from 5 to 30 yr - not only decades; the ending year also varies . In this way, we uncover a whole unexplored space of values for the global warming rate, and access the full picture. Additionally, stairstep averaging and linear least squares fitting to determine climatic trends have been sofar exclusive. We propose here an original hybrid method which combines both approaches in order to derive a new type of climatic trend. We find that there is an overall acceleration of the global warming whatever the value of the averaging period, and that 99.9% of the 3029 Earth's climatic irregular staircases are rising. Graphical evidence is also given that choosing an El Nino year as starting year gives lower global warming rates - except if there is a volcanic cooling in parallel. Our rates agree and generalize several results mentioned in the literature. PMID- 26813868 TI - Recurrent neutrophilic dermatosis of the face: A report of two cases and review of the published work. AB - Recurrent neutrophilic dermatosis of the face is a disease that is morphologically and histopathologically compatible with Sweet's syndrome, but is distributed on the face without fever, laboratory abnormalities or associated disorders. At present, it is unclear whether our cases belong to the chronic and mild variant of Sweet's syndrome or are independent entities. Here, we present two cases of recurrent neutrophilic dermatosis of the face with good response to systemic corticosteroids or potassium iodine, as well as those of cases reported in the published work. PMID- 26813870 TI - Recovery position cuts hospital admissions in unconscious children, study shows. PMID- 26813869 TI - Comparison of two different techniques for balloon sizing in percutaneous mitral balloon valvuloplasty: which is preferable? AB - BACKGROUND: Percutaneous balloon mitral valvuloplasty (BMV) is an important option for the treatment of mitral valve stenosis. The crux of this process is choosing the appropriate Inoue balloon size. There are two methods to do this. One is an empirical formula based on the patient's height, and other is to choose according to the maximal inter-commissural distance of the mitral valve provided by echocardiography. METHODS: The study, performed between January 2006 and December 2011, included 128 patients who had moderate to severe mitral stenosis and whose valve morphology was suitable for BMV. Patients were randomised into two groups. One group was allocated to conventional height-based balloon reference sizing (the HBRS group) and the other was allocated to balloons sized by the echocardiographic measurement of the diastolic inter-commissural diameter (the EBRS group). RESULTS: BMV was assessed as successful in 60 (92.3%) patients in the HBRS group and in 61 (96.8%) in the EBRS group (p = 0.03). The mean of the calculated balloon reference sizes was significantly higher in the HBRS than in the EBRS group [26.3 +/- 1.2 mm, 95% confidence interval (CI): 26.1-26.6 vs 25.2 +/- 1.1, 95% CI: 25.0-25.4, respectively; p = 0.007]. Final mitral valve areas (MVA) were larger and mitral regurgitation (MR) gt; 2+ was less in the EBRS group (p = 0.02 and p = 0.05, respectively) CONCLUSIONS: EBRS is a method that is independent of body structure. Choosing Inoue balloon size by measuring maximal diastolic annulus diameter by echocardiography for BMV may be an acceptable method for appropriate final MVA and to avoid risk of significant MR. PMID- 26813873 TI - Mucoepidermoid Carcinoma of Floor of the Mouth - A Rarity. AB - Mucoepidermoid Carcinoma (MEC) is one of the most commonly occurring malignant salivary gland neoplasm, and contributes 2.8%-15% of all salivary gland tumours. More than half of these cases involve the major salivary glands, primarily the parotid glands and minor salivary glands. Sublingual salivary glands neoplasms are very rare and constitute 0.5% and 1% of all epithelial salivary tumours and approximately 1.5% of the major salivary glands carcinomas. Here we describe a case report of low grade mucoepidermoid carcinoma in the floor of the mouth in a 70-year-old female patient that was mimicking like a ranula clinically. PMID- 26813872 TI - Correlating confocal microscopy and atomic force indentation reveals metastatic cancer cells stiffen during invasion into collagen I matrices. AB - Mechanical interactions between cells and their microenvironment dictate cell phenotype and behavior, calling for cell mechanics measurements in three dimensional (3D) extracellular matrices (ECM). Here we describe a novel technique for quantitative mechanical characterization of soft, heterogeneous samples in 3D. The technique is based on the integration of atomic force microscopy (AFM) based deep indentation, confocal fluorescence microscopy, finite element (FE) simulations and analytical modeling. With this method, the force response of a cell embedded in 3D ECM can be decoupled from that of its surroundings, enabling quantitative determination of the elastic properties of both the cell and the matrix. We applied the technique to the quantification of the elastic properties of metastatic breast adenocarcinoma cells invading into collagen hydrogels. We found that actively invading and fully embedded cells are significantly stiffer than cells remaining on top of the collagen, a clear example of phenotypical change in response to the 3D environment. Treatment with Rho-associated protein kinase (ROCK) inhibitor significantly reduces this stiffening, indicating that actomyosin contractility plays a major role in the initial steps of metastatic invasion. PMID- 26813874 TI - Preventing falls in hospitals. PMID- 26813875 TI - Kinematic Adaptive Deep Brain Stimulation for Resting Tremor in Parkinson's Disease. PMID- 26813876 TI - Association of Decreased Expression of Serum miR-9 with Poor Prognosis of Oral Squamous Cell Carcinoma Patients. AB - BACKGROUND: Dysregulation of miR-9 is a common feature of many types of cancers, including oral squamous cell carcinoma (OSCC). However, whether the expression level of serum miR-9 is changed in patients with OSCC remains unknown. MATERIAL/METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression level of serum miR-9 in OSCC patients, oral leukoplakia (OLK) patients, and healthy volunteers, then we evaluated the association between serum miR-9 expression level and clinical outcome of OSCC patients. RESULTS: The expression level of serum miR-9 was significantly downregulated in patients with OSCC or OLK in comparison with healthy controls (P<0.01). Serum miR-9 expression level was associated with various clinicopathological parameters, including T stage (P=0.013), lymph node metastasis (P=0.002), and TNM stage (P=0.007). In addition, the OSCC patients in the low serum miR-9 expression group had poorer overall survival rate (P=0.022) and disease-free survival rate (P=0.004) compared with those in the high serum miR-9 expression group. Multivariate analysis showed that serum miR-9 was an independent prognostic factor for OSCC. CONCLUSIONS: Serum miR-9 was downregulated in patients with OSCC and patients with OLK. In addition, low serum miR-9 was correlated with poor prognosis of OSCC, indicating miR-9 might play a tumor suppressive role in OSCC and can serve as a promising biomarker for this deadly disease. PMID- 26813877 TI - Enzyme- and pH-Responsive Microencapsulated Nanogels for Oral Delivery of siRNA to Induce TNF-alpha Knockdown in the Intestine. AB - Inflammatory bowel diseases (IBD) manifest from excessive intestinal inflammation. Local delivery of siRNA that targets these inflammatory cytokines would provide a novel treatment approach. Microencapsulated nanogels are designed and validated as platforms for oral delivery of siRNA targeting TNF-alpha, a common clinical target of IBD treatments. The preferred platform was designed to (i) protect siRNA-loaded nanogels from the harsh acidic environment of the upper GI tract and (ii) enzymatically degrade and release the nanogels once the carrier has reached the intestinal region. This platform consists of microgels composed of poly(methacrylic acid-co-N-vinyl-2-pyrrolidone) (P[MAA-co-NVP]) cross-linked with a trypsin-degradable peptide linker. The P(MAA-co-NVP) backbone is designed to collapse around and protect encapsulated nanogel from degradation at the low pH levels seen in the stomach (pH 2-4). At pH levels of 6-7.5, as typically observed in the intestine, the P(MAA-co-NVP) matrix swells, potentially facilitating diffusion of intestinal fluid and degradation of the matrix by intestinal enzymes such as trypsin, thus "freeing" the therapeutic nanogels for delivery and cellular uptake within the intestine. TNF-alpha siRNA-loaded nanogels released from this platform were capable of inducing potent knockdown of secreted TNF-alpha levels in murine macrophages, further validating the potential for this approach to be used for the treatment of IBD. PMID- 26813878 TI - Nanoparticle-Mediated Physical Exfoliation of Aqueous-Phase Graphene for Fabrication of Three-Dimensionally Structured Hybrid Electrodes. AB - Monodispersed polypyrrole (PPy) nanospheres were physically incorporated as guest species into stacked graphene layers without significant property degradation, thereby facilitating the formation of unique three-dimensional hybrid nanoarchitecture. The electrochemical properties of the graphene/particulate PPy (GPPy) nanohybrids were dependent on the sizes and contents of the PPy nanospheres. The nanohybrids exhibited optimum electrochemical performance in terms of redox activity, charge-transfer resistance, and specific capacitance at an 8:1 PPy/graphite (graphene precursor) weight ratio. The packing density of the alternately stacked nanohybrid structure varied with the nanosphere content, indicating the potential for high volumetric capacitance. The nanohybrids also exhibited good long-term cycling stability because of a structural synergy effect. Finally, fabricated nanohybrid-based flexible all-solid state capacitor cells exhibited good electrochemical performance in an acidic electrolyte with a maximum energy density of 8.4 Wh kg(-1) or 1.9 Wh L(-1) at a maximum power density of 3.2 kW kg(-1) or 0.7 kW L(-1); these performances were based on the mass or packing density of the electrode materials. PMID- 26813879 TI - Autoimmune Recurrence as a Cause of Adrenal Gland Graft Loss? PMID- 26813880 TI - Characterization of extracellular amylase produced by haloalkalophilic strain Kocuria sp. HJ014. AB - The haloalkaliphilic bacterium Kocuria sp. (HJ014) has the ability to produce extracellular amylase. The aim of this study was to purify and characterize this protein. The amylase enzyme with a specific activity of 753,502 U/mg was purified 5.7- fold using Sepharose 4B and Sephacryl S-300 gel filtration columns. The molecular weight of the enzyme was 45,000 Da as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The amylase showed maximum activity at pH 9 and 50 degrees C in the presence of 3.5 M NaCl. The Km was 3.0 mg/ml and Vmax 90.09 U/ml. It was found that extracellular amylase from Kocuria sp. has a high industrial potential. PMID- 26813881 TI - Group discussions with structured reminiscence and a problem-based method as an intervention to prevent depressive symptoms in older people. AB - AIMS AND OBJECTIVES: To evaluate the effect of group discussions, in which structured reminiscence and a problem-based method were used, on depressive symptoms, quality of life and self-rated health among older people. BACKGROUND: Depressive symptoms in older people have a considerable impact on self-rated health and quality of life, with a high rate of co-morbidity and mortality. As the ageing population is growing, late-life depression is becoming an important public health problem and there is a need to find preventive interventions to avert unnecessary suffering. DESIGN: The study was quasi-experimental, with a one group pretest-post-test design and follow-up after one year. METHODS: Initially, a questionnaire was sent to the total population of 55-80-year-old retirees in a community in the northeast of Sweden, (n = 679). The questionnaire concerned demographics and covered areas such as health, depression and quality of life. The intervention consisted of group discussions where structured reminiscence and a problem-based method were used. The participants (n = 18) met 10 times under the guidance of a group-leader, a registered nurse educated in the method. Each session had different themes with a focus on positive memories but also on the present situation and the future. Parametric, nonparametric tests and content analysis were used. RESULTS: Participants evaluated the intervention positively, showed a decrease in depressive symptoms, an increase in self-rated health and experienced an increased autonomy. No long- lasting effect was seen. CONCLUSION: Group discussions where structured reminiscence and a problem-based method are used might be an option to prevent depressive symptoms in older people. RELEVANCE TO CLINICAL PRACTICE: This method might provide an opportunity for older people with depressive symptoms to improve their quality of life, however, to maintain the positive outcome the intervention should probably be continuous. PMID- 26813882 TI - Parallel Stitching of 2D Materials. AB - Diverse parallel stitched 2D heterostructures, including metal-semiconductor, semiconductor-semiconductor, and insulator-semiconductor, are synthesized directly through selective "sowing" of aromatic molecules as the seeds in the chemical vapor deposition (CVD) method. The methodology enables the large-scale fabrication of lateral heterostructures, which offers tremendous potential for its application in integrated circuits. PMID- 26813883 TI - Integrated double mulching practices optimizes soil temperature and improves soil water utilization in arid environments. AB - Water shortage threatens agricultural sustainability in many arid and semiarid areas of the world. It is unknown whether improved water conservation practices can be developed to alleviate this issue while increasing crop productivity. In this study, we developed a "double mulching" system, i.e., plastic film coupled with straw mulch, integrated together with intensified strip intercropping. We determined (i) the responses of soil evaporation and moisture conservation to the integrated double mulching system and (ii) the change of soil temperature during key plant growth stages under the integrated systems. Experiments were carried out in northwest China in 2009 to 2011. Results show that wheat-maize strip intercropping in combination with plastic film and straw covering on the soil surface increased soil moisture (mm) by an average of 3.8 % before sowing, 5.3 % during the wheat and maize co-growth period, 4.4 % after wheat harvest, and 4.9 % after maize harvest, compared to conventional practice (control). The double mulching decreased total evapotranspiration of the two intercrops by an average of 4.6 % (P < 0.05), compared to control. An added feature was that the double mulching system decreased soil temperature in the top 10-cm depth by 1.26 to 1.31 degrees C in the strips of the cool-season wheat, and by 1.31 to 1.51 degrees C in the strips of the warm-season maize through the 2 years. Soil temperature of maize strips higher as 1.25 to 1.94 degrees C than that of wheat strips in the top 10-cm soil depth under intercropping with the double mulching system; especially higher as 1.58 to 2.11 degrees C under intercropping with the conventional tillage; this allows the two intercrops to grow in a well "collaborative" status under the double mulching system during their co-growth period. The improvement of soil moisture and the optimization of soil temperature for the two intercrops allow us to conclude that wheat-maize intensification with the double mulching system can be used as an effective farming model in alleviating water shortage issues experiencing in water shortage areas. PMID- 26813884 TI - Spa therapy for elderly: a retrospective study of 239 older patients with osteoarthritis. AB - Very few studies tested the effectiveness of spa therapy in older patients with osteoarthritis. Therefore, we aimed to evaluate the short-term effects of spa therapy in patients aged 65 years and older with generalized, knee, hip, and cervical and lumbar spine osteoarthritis. In an observational retrospective study design at the Medical Ecology and Hydroclimatology Department of Istanbul Medical Faculty, we analyzed the records of 239 patients aged over 65 years with the diagnosis of all types of osteoarthritis who were prescribed a spa therapy course in some spa resorts in Turkey between 7 March 2002 and 31 December 2012. They travelled to a spa resort where they stayed at a thermal spa hotel and followed the usual therapy packages for 2 weeks. Patients were assessed by an experienced physician within a week before the spa journey and within a week after the completion of the spa therapy. Compared with baseline in whole sample, statistically significant improvements were observed in pain (visual analog scale, VAS), patient and physician global assessments (VAS), Health Assessment Questionnaire disability index (HAQ-DI), Lequesne algofunctional index (LAFI) for knee, Western Ontario and McMaster Universities index (WOMAC), Waddell disability index (WDI), and Neck Pain and Disability Scale (NPAD). According to Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT OARSI) Set of Responder Criteria, responder rate were 63.8 % (51/80) in generalized, 52 % (13/25) in knee, 50 % (2/4) in hip, 66.7 % (8/12) in lumbar, and 100 % (6/6) in cervical osteoarthritis subgroups. Spa therapy improved pain and physical functional status in older patients with osteoarthritis, especially generalized osteoarthritis and multiple joint osteoarthritis with involvement of knee. This improvement was clinically important in majority of the patients. To confirm the results of this preliminary study, there is a need of a randomized controlled clinical study comparing spa therapy with usual care in the elderly population with osteoarthritis. PMID- 26813886 TI - Role of Lipid Composition on the Interaction between a Tryptophan-Rich Protein and Model Bacterial Membranes. AB - The interaction between tryptophan-rich puroindoline proteins and model bacterial membranes at the air-liquid interface has been investigated by FTIR spectroscopy, surface pressure measurements, and Brewster angle microscopy. The role of different lipid constituents on the interactions between lipid membrane and protein was studied using wild type (Pin-b) and mutant (Trp44 to Arg44 mutant, Pin-bs) puroindoline proteins. The results show differences in the lipid selectivity of the two proteins in terms of preferential binding to specific lipid head groups in mixed lipid systems. Pin-b wild type was able to penetrate mixed layers of phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) head groups more deeply compared to the mutant Pin-bs. Increasing saturation of the lipid tails increased penetration and adsorption of Pin-b wild type, but again the response of the mutant form differed. The results provide insight as to the role of membrane architecture, lipid composition, and fluidity on antimicrobial activity of proteins. Data show distinct differences in the lipid binding behavior of Pin-b as a result of a single residue mutation, highlighting the importance of hydrophobic and charged amino acids in antimicrobial protein and peptide activity. PMID- 26813887 TI - Therapeutic microRNA Delivery Strategies with Special Emphasis on Cancer Therapy and Tumorigenesis: Current Trends and Future Challenges. AB - BACKGROUND: Over the decade, miRNAs are the most important molecules for the biopharmaceutical industry due to their relation with several human diseases. Presently, the phase-II clinical trial has been initiated for the first miRNA based therapeutics ("Miravirsen") to treat HCV infection. It has been expected that many more miRNA-based therapeutics will enter the clinical trials. Therefore, it is important to develop different kinds of novel delivery systems with better efficacy and more efficiency, but fewer side effects. METHODS: We have undertaken a structured search of bibliographic databases for peer-reviewed research literature to solve our review question. Literature survey was performed widely to write this review article. RESULTS: In this review, we have discussed the various types of miRNA delivery systems such as viral vectors, lipid-based systems, nanocarriers, and LNA-customized DNA delivery without any delivery mediated agent. Current status, technical support, and the future challenges for miRNA-based delivery are also discussed. CONCLUSION: Recent development and understanding of miRNA had shown the therapeutic potentiality of miRNA. PMID- 26813885 TI - Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus. AB - Respiratory syncytial virus (RSV) infection is a major cause of severe lower respiratory illness in infants and young children, but the underlying mechanisms responsible for viral pathogenesis have not been fully elucidated. To date, no drugs or vaccines have been employed to improve clinical outcomes for RSV infected patients. In this paper, we report that angiotensin-converting enzyme-2 (ACE2) protected against severe lung injury induced by RSV infection in an experimental mouse model and in pediatric patients. Moreover, ACE2 deficiency aggravated RSV-associated disease pathogenesis, mainly by its action on the angiotensin II type 1 receptor (AT1R). Furthermore, administration of a recombinant ACE2 protein alleviated the severity of RSV-induced lung injury. These findings demonstrate that ACE2 plays a critical role in preventing RSV induced lung injury, and suggest that ACE2 is a promising potential therapeutic target in the management of RSV-induced lung disease. PMID- 26813888 TI - Restricting mutualistic partners to enforce trade reliance. AB - Mutualisms are cooperative interactions between members of different species, often involving the trade of resources. Here, we suggest that otherwise cooperative mutualists might be able to gain a benefit from actively restricting their partners' ability to obtain resources directly, hampering the ability of the restricted partner to survive and/or reproduce without the help of the restricting mutualist. We show that (i) restriction can be favoured when it makes the resources of the restricting individual more valuable to their partner, and thus allows them to receive more favourable terms of trade; (ii) restriction maintains cooperation in conditions where cooperative behaviour would otherwise collapse; and (iii) restriction can lead to either an increase or decrease in a restricted individual's fitness. We discuss the applicability of this scenario to mutualisms such as those between plants and mycorrhizal fungi. These results identify a novel conflict in mutualisms as well as several public goods dilemmas, but also demonstrate how conflict can help maintain cooperation. PMID- 26813891 TI - Caffeine Consumption and Cardiovascular Risks: Little Cause for Concern. PMID- 26813889 TI - Consumption of Caffeinated Products and Cardiac Ectopy. AB - BACKGROUND: Premature cardiac contractions are associated with increased morbidity and mortality. Though experts associate premature atrial contractions (PACs) and premature ventricular contractions (PVCs) with caffeine, there are no data to support this relationship in the general population. As certain caffeinated products may have cardiovascular benefits, recommendations against them may be detrimental. METHODS AND RESULTS: We studied Cardiovascular Health Study participants with a baseline food frequency assessment, 24-hour ambulatory electrocardiography (Holter) monitoring, and without persistent atrial fibrillation. Frequencies of habitual coffee, tea, and chocolate consumption were assessed using a picture-sort food frequency survey. The main outcomes were PACs/h and PVCs/hour. Among 1388 participants (46% male, mean age 72 years), 840 (61%) consumed >=1 caffeinated product per day. The median numbers of PACs and PVCs/h and interquartile ranges were 3 (1-12) and 1 (0-7), respectively. There were no differences in the number of PACs or PVCs/h across levels of coffee, tea, and chocolate consumption. After adjustment for potential confounders, more frequent consumption of these products was not associated with ectopy. In examining combined dietary intake of coffee, tea, and chocolate as a continuous measure, no relationships were observed after multivariable adjustment: 0.48% fewer PACs/h (95% CI -4.60 to 3.64) and 2.87% fewer PVCs/h (95% CI -8.18 to 2.43) per 1-serving/week increase in consumption. CONCLUSIONS: In the largest study to evaluate dietary patterns and quantify cardiac ectopy using 24-hour Holter monitoring, we found no relationship between chronic consumption of caffeinated products and ectopy. PMID- 26813892 TI - Blaming Machismo: How the Social Imaginary is Failing Men with HIV in Santa Cruz, Bolivia. AB - Drawing from an ethnography of HIV care in Santa Cruz, Bolivia, in this article I explore how the social imaginary surrounding gender relations shapes men's experiences of seeking care for and living with HIV. Popular understandings of gender relations, which draw heavily on the machismo concept, intersect with a global health master narrative that frames women as victims in the AIDS epidemic in a way that generates a strong sentiment of blaming machismo within local HIV/AIDS-related services. Statements such as, "it's because of machismo" are used to explain away epidemiological trends. Participant observation in the context of HIV care, coupled with illness narrative interviews, illuminate how blaming machismo shapes men's experiences of care and the ways that they feel excluded from various forms of support. Thus, the illness experiences of men with HIV problematize the machismo concept and how it is drawn upon in the context of care. PMID- 26813893 TI - Caviibacter abscessus gen. nov., sp. nov., a member of the family Leptotrichiaceae isolated from guinea pigs (Cavia porcellus). AB - A pleomorphic, Gram-stain-negative, rod-shaped, indole-, oxidase- and catalase negative, non-spore-forming, non-motile bacterium was originally isolated from the mandibular lymph node of a guinea pig and deposited as Streptobacillus moniliformis CCUG 39713 in 1998. A second strain, 151011837, was isolated from an identical lesion in a guinea pig in Germany in 2015. On the basis of 16S rRNA gene sequence analyses, these strains displayed highest sequence similarities with Sneathia sanguinegens NTS65407T (93.4%) and 'Sneathia amnii' Sn35 (93.2%), followed by Streptobacillus moniliformis DSM 12112T (91.3%), 'Streptobacillus ratti' OGS16 (91.2%), Streptobacillus notomytis AHL370-1T (91.0%), Streptobacillus hongkongensis HKU33T (90.9%) and Streptobacillus felis 131000547T (90.9%). Levels of sequence similarity with all other members of the family Leptotrichiaceae were <89%. Results of phylogenetic analyses of strains CCUG 39713T and 151011837, based on gyrB, groEL and recA nucleotide and deduced amino acid sequences, were highly similar, as the topologies of all trees were virtually identical. DNA relatedness values derived from average nucleotide identities calculated for comparisons between strain CCUG 39713T and the type strains of Sneathia sanguinegens and Streptobacillus moniliformis, respectively, were 72.05 and 70.42%. The genomes of CCUG39713T and 151011837 shared 99.57% average nucletide identity. The chemotaxonomic and physiological data for strains CCUG 39713T and 151011837 were in congruence with other closely related members of the family Leptotrichiaceae, with highly similar enzyme activities and fatty acid profiles. Matrix-assisted laser desorption ionization time-of-flight MS analysis was capable of clearly discriminating strains CCUG 39713T and 151011837 from all taxa of the family Leptotrichiaceae with validly published names. On the basis of these data, the novel taxon Caviibacter abscessus gen. nov., sp. nov. is proposed. The type strain of Caviibacter abscessus is CCUG 39713T (=DSM 101949T); 151011837 (DSM 101950) is an additional strain of the species. PMID- 26813895 TI - The Journal in 2015. PMID- 26813894 TI - Quality of life in women who were exposed to domestic violence during pregnancy. AB - BACKGROUND: Quality of life in pregnant women is an important issue both for women's and fetus' health. This study aimed to examine quality of life in a group of women who were exposed to domestic violence during pregnancy. METHODS: This was a cross sectional study of quality of life among a consecutive sample of pregnant women attending to a teaching hospital in Lorestan, Iran. Women were screened for experiencing violence using the Abuse Assessment Screen (AAS) questionnaire and were categorized as psychological abused, physical abused and non-abused groups. Quality of life was assessed using the Short-Form 36 Health Survey (SF-36). One-way analysis of variance and t-test were used to examine differences in quality of life in the study sub-samples. In addition logistic regression analyses were performed to investigate the association between general health and mental health and independent variables including age, education, parity and type of violence. RESULTS: In all 266 pregnant women were approached, of which 230 (86.5%) agreed to participate in the study. Of these, 149 women (64.8%) reported that they had experienced either physical or psychological violence during pregnancy. A significant difference between abused and non-abused groups was identified, with the abused group recording lower mean scores on all sub-scales with the exception of the bodily pain (p = 0.27). In addition comparing quality of life between physical and psychological abused groups, women who reported physical violence recorded lower mean scores for physical functioning, role physical, bodily pain and general health, while women reporting psychological abuse had lower mean scores on social functioning, role emotional, vitality and mental health. Comparison between the physically and psychologically abused groups indicated significant differences only for role physical (p = 0.04), bodily pain (p = 0.003) and general health (p = 0.04). After adjusting for age, parity, and education, physical abuse was associated with poor physical health (OR = 2.13, 95% CI = 1.05-4.36, p = 0.03), while emotional abuse was significantly associated with poor mental health (OR = 1.89, 95% CI = 1.09-3.84, p = 0.04). CONCLUSION: Domestic violence against women during pregnancy in Iran was evident and this had significant adverse association with their quality of life. Indeed health care professionals involved in the care of women need to be aware of the extent of the problem and consider how it may be impacting on the women in their care. PMID- 26813898 TI - Editor's Note. PMID- 26813897 TI - Intrinsically flawed health systems by design. PMID- 26813899 TI - Coronary computed tomography angiography and its increasing application in day to day cardiology practice. AB - Coronary artery disease (CAD) is the leading single cause of death in Australia affecting around 1.4 million people. Coronary computed tomography angiography has an established role in the assessment of patients with low to intermediate pretest probability for CAD who have chest pain and is typically used with the aim to rule out significant coronary artery stenosis. Use was initially limited because of concerns over radiation exposure, a Medicare rebate restricted to specialist referrals and an absence of data supporting its use as an alternative to functional testing in patients with chest pain. Recent advances in scanner technology and image sequencing, along with data from randomised control trials, have addressed these issues and indicate that coronary computed tomography angiography will play a greater role in the assessment of CAD in the coming years. PMID- 26813900 TI - Placental involvement by non-Hodgkin lymphoma in a Crohn disease patient on long term thiopurine therapy. AB - We report the first published case of aggressive diffuse large B-cell (non Hodgkin) lymphoma in a 35-year-old pregnant woman who had Crohn disease and was taking long-term thiopurine therapy: the patient developed placental insufficiency, and there was intrauterine fetal death. PMID- 26813890 TI - Dietary alpha-Linolenic Acid, Marine omega-3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvencion con DIeta MEDiterranea (PREDIMED) Study. AB - BACKGROUND: Epidemiological evidence suggests a cardioprotective role of alpha linolenic acid (ALA), a plant-derived omega-3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine omega-3 fatty acids (long-chain n-3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all-cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long-chain n-3 polyunsaturated fatty acids (>=500 mg/day). METHODS AND RESULTS: We longitudinally evaluated 7202 participants in the PREvencion con DIeta MEDiterranea (PREDIMED) trial. Multivariable-adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9-y follow-up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56-0.92) for all-cause mortality and 0.95 (95% CI 0.58-1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long chain n-3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67 1.05) for all-cause mortality, 0.61 (95% CI 0.39-0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29-0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22-1.01) for sudden cardiac death. The highest reduction in all-cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45-0.87]). CONCLUSIONS: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all-cause mortality, whereas protection from cardiac mortality is limited to fish-derived long-chain n-3 polyunsaturated fatty acids. CLINICAL TRIAL REGISTRATION: URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639. PMID- 26813902 TI - Positive beliefs and privacy concerns shape the future for the Personally Controlled Electronic Health Record. AB - The uptake of the Personally Controlled Electronic Health Record (PCEHR) has been slowly building momentum in Australia. The purpose of the PCEHR is to collect clinically important information from multiple healthcare providers to provide a secure electronic record to patients and their authorised healthcare providers that will ultimately enhance the efficiency and effectiveness of healthcare delivery. Reasons for the slow uptake of the PCEHR and future directions to improve its usefulness is discussed later. PMID- 26813901 TI - Value of electrocardiograms ordered by junior medical officers in the emergency department. AB - The diagnostic rationale for patients with chest pain requires an electrocardiogram (ECG) often limited by low pretest values and widely variable post-test values. We assess the value of ECG ordered and interpreted by internal medicine junior medical officers in our emergency department (ED). Participants enrolled in this study included patients who presented to the ED for chest pain between June and October 2014. Seventeen leads ECG were performed systematically when an ECG was judged required by the medical officer in charge and interpreted by a blinded medical officer and ED attending. Ultrasensitive troponin T (usTrop T) and creatinine were also withdrawn. Junior medical officers ordered ECG more commonly for atypical chest pain (57 vs 43%, P = 0.049). Univariate and multivariate analysis did not demonstrate a statistically discordant diagnosis between the medical officer and the attending throughout the study period and between the different rotations. We demonstrated 97% sensitivity, 95% specificity, 92% positive predictive value, 98% negative predictive value and 96% accuracy. Our junior medical officers demonstrated an overall high proficiency in the clinical and bedside setting. This finding reinforces our ECG education in the undergraduate curriculum, highlights the importance of the intensive recapitulation sessions undergone at the beginning of the training programme and our daily internal medicine staff discussions rarely performed in other EDs as reported with our experience. PMID- 26813903 TI - Medicine: in need of culture change. AB - Compared with other health professionals and the general population, doctors and medical students reported higher rates of psychological distress, burnout, diagnosed mental illness, suicidal ideation and attempted suicide. Where possible, the problematic and unnecessarily stressful aspects of working as a doctor must be improved. Collectively, we must change the often toxic culture of medicine into a culture that promotes a nurturing and supportive approach to teaching and supervision. The goal should be to develop medical practices that facilitate well-being and quality of life, where sustainable medical careers can develop and better serve the community. PMID- 26813904 TI - Cutaneous lichen amyloidosis in multiple endocrine neoplasia. PMID- 26813905 TI - A case of steroid-responsive valerian-associated hepatitis. PMID- 26813906 TI - Acrokeratosis paraneoplastica (Bazex syndrome) associated with metastatic cutaneous squamous cell carcinoma. PMID- 26813907 TI - Punishment for a medical malpractice in Japan. PMID- 26813908 TI - Sick number medicine. PMID- 26813909 TI - Building the community of patient-centred care practice across all sectors of health care and health professional education. PMID- 26813910 TI - Author reply. PMID- 26813914 TI - A Review and Update of Treatment Options and Controversies in the Management of Hepatocellular Carcinoma. AB - OBJECTIVE: To review the current management, outline recent advances and address controversies in the management of hepatocellular carcinoma (HCC). SUMMARY OF BACKGROUND DATA: The treatment of HCC is multidisciplinary involving hepatologists, surgeons, medical oncologists, radiation oncologists, radiologists, interventional radiologists, and other disciplines. Each of these disciplines brings its unique perspective and differing opinions that add to controversies in the management of HCC. METHODS: A focused literature review was performed to identify recent studies on the management of HCC and thereby summarize relevant information on the various therapeutic modalities and controversies involved in the treatment of HCC. RESULTS: The main treatment algorithms continue to rely on hepatic resection or transplantation with controversies involving patients harboring early stage disease and borderline hepatic function. The other treatment strategies include locoregional therapies, radiation, and systemic therapy used alone or in combination with other treatment modalities. Recent advances in locoregional therapies, radiation, and systemic therapies have provided better therapeutic options with curative intent potential for some locoregional therapies. Further refinements in combination therapies such as algorithms consisting of locoregional therapies and systemic or radiation therapies are likely to add additional options and improve survival. CONCLUSIONS: The management of HCC has witnessed significant strides with advances in existing options and introduction of several new treatment modalities of various combinations. Further refinements in these treatment options combined with enrollment in clinical trials are essential to improve the management and outcomes of patients with HCC. PMID- 26813911 TI - Neisseria cinerea isolates can adhere to human epithelial cells by type IV pilus independent mechanisms. AB - In pathogenic Neisseria species the type IV pili (Tfp) are of primary importance in host-pathogen interactions. Tfp mediate initial bacterial attachment to cell surfaces and formation of microcolonies via pilus-pilus interactions. Based on genome analysis, many non-pathogenic Neisseria species are predicted to express Tfp, but aside from studies on Neisseria elongata, relatively little is known about the formation and function of pili in these organisms. Here, we have analysed pilin expression and the role of Tfp in Neisseria cinerea. This non pathogenic species shares a close taxonomic relationship to the pathogen Neisseria meningitidis and also colonizes the human oropharyngeal cavity. Through analysis of non-pathogenic Neisseria genomes we identified two genes with homology to pilE, which encodes the major pilin of N. meningitidis. We show which of the two genes is required for Tfp expression in N. cinerea and that Tfp in this species are required for DNA competence, similar to other Neisseria. However, in contrast to the meningococcus, deletion of the pilin gene did not impact the association of N. cinerea to human epithelial cells, demonstrating that N. cinerea isolates can adhere to human epithelial cells by Tfp-independent mechanisms. PMID- 26813915 TI - Predicting Mid-term All-cause Mortality in Patients Undergoing Elective Endovascular Repair of a Descending Thoracic Aortic Aneurysm. AB - INTRODUCTION: All-cause mortality in patients after repair of aortic aneurysms of the descending thoracic aorta thoracic endovascular aortic repair (TEVAR) is relatively high at mid-term follow-up. The aim of this study was to derive and validate a system that could predict all-cause mortality after TEVAR to aid with patient selection. METHODS: The MOTHER database contained 625 patients that underwent elective surgery for descending thoracic aortic aneurysms. Univariate analysis identified preoperative factors associated with mid-term all-cause mortality, and a Cox proportional hazards model was developed. The model was internally validated using Kaplan-Meier comparison of observed vs predicted mortality. External validation was performed using a data set from the University of Florida College of Medicine. RESULTS: There were 625 patients that underwent TEVAR for descending thoracic aortic aneurysm in the MOTHER database and 231 in the University of Florida College of Medicine validation set. The mid-term mortality rate at 6 years of follow-up was 34.4% and 34%, respectively. The all cause mortality risk score was calculated using 0.0398 * (age) + 0.516 * (renal insufficiency) + 0.46 * (previous cerebrovascular disease) + 0.352 * (prior tobacco use) + 0.376 * (number of devices >2) + 0.016 * (maximum aneurysm diameter). Using this score, low-, medium-, and high-risk groups were defined, with predicted survival at 5 years of 80%, 60%, and 40%. Patients at high risk of mid-term all-cause death were identified in the validation cohort using the prediction rule. CONCLUSIONS: Identifying patients with a limited life expectancy after TEVAR is possible using a preoperative risk-stratification system. This information can be used to inform decision making regarding when and whether to proceed with TEVAR. PMID- 26813917 TI - Filippi Syndrome: Report of a Rare Case. AB - Filippi syndrome is an autosomal recessive condition characterized by syndactyly of fingers and toes, microcephaly, growth retardation and abnormal facies. We are describing a boy who presented with syndactyly, mental retardation, microcephaly, depressed nasal bridge and growth retardation. In addition he had some dental abnormalities like missing bilateral lateral incisors and delayed eruption of teeth. We concluded it to be Filippi syndrome by studying pathognomic clinical features and reviewed the literature. This is the second case report from India. PMID- 26813916 TI - A Biocompatible and Biodegradable Protein Hydrogel with Green and Red Autofluorescence: Preparation, Characterization and In Vivo Biodegradation Tracking and Modeling. AB - Because of its good biocompatibility and biodegradability, albumins such as bovine serum albumin (BSA) and human serum albumin (HSA) have found a wide range of biomedical applications. Herein, we report that glutaraldehyde cross-linked BSA (or HSA) forms a novel fluorescent biological hydrogel, exhibiting new green and red autofluorescence in vitro and in vivo without the use of any additional fluorescent labels. UV-vis spectra studies, in conjunction with the fluorescence spectra studies including emission, excitation and synchronous scans, indicated that three classes of fluorescent compounds are presumably formed during the gelation process. SEM, FTIR and mechanical tests were further employed to investigate the morphology, the specific chemical structures and the mechanical strength of the as-prepared autofluorescent hydrogel, respectively. Its biocompatibility and biodegradability were also demonstrated through extensive in vitro and in vivo studies. More interestingly, the strong red autofluorescence of the as-prepared hydrogel allows for conveniently and non-invasively tracking and modeling its in vivo degradation based on the time-dependent fluorescent images of mice. A mathematical model was proposed and was in good agreement with the experimental results. The developed facile strategy to prepare novel biocompatible and biodegradable autofluorescent protein hydrogels could significantly expand the scope of protein hydrogels in biomedical applications. PMID- 26813918 TI - Tumour Necrosis Factor-alpha (TNF-alpha) and its soluble receptor type 1 (sTNFR I) in human active and healed leishmaniases. AB - The role of tumour necrosis factor-alpha (TNF-alpha) is not fully understood in human leishmaniasis. We analysed the alterations in the levels of TNF-alpha, soluble TNF receptor type 1 (sTNFR I), IL-17 and IL-22 productions in active and healed leishmaniases. Blood samples were collected from volunteers with active cutaneous leishmaniasis (ACL), the same subjects after lesion healing (healed CL = HCL), volunteers with active visceral leishmaniasis (AVL), healed VL (HVL) and healthy controls. Levels of cytokines were titrated on Leishmania Ag-stimulated PBMC culture. The mean level of TNF-alpha production from stimulated cells was significantly higher in ACL than controls (P < 0.001) and significantly reduced after treatment in HCL volunteers (P < 0.05). The mean level of sTNFR I production was significantly higher in ACL than controls (P < 0.001) and significantly reduced after treatment in HCL volunteers (P < 0.05). The mean level of IL-22 production in AVL was significantly higher than controls (P < 0.05) and was significantly lower in HVL compared with AVL (P < 0.001) and controls (P < 0.05). The levels of TNF-alpha (P = 0.0025) and sTNFR I (P < 0.01) productions from PBMCs showed significant decreasing trend after treatment in each CL volunteer. Reduction in TNF-alpha is associated with clinical response to treatment and healing of CL lesions due to L. major. PMID- 26813919 TI - Pd(II)-catalysed meta-C-H functionalizations of benzoic acid derivatives. AB - Benzoic acids are highly important structural motifs in drug molecules and natural products. Selective C-H bond functionalization of benzoic acids will provide synthetically useful tools for step-economical organic synthesis. Although direct ortho-C-H functionalizations of benzoic acids or their derivatives have been intensely studied, the ability to activate meta-C-H bond of benzoic acids or their derivatives in a general manner via transition-metal catalysis has been largely unsuccessful. Although chelation-assisted meta-C-H functionalization of electron-rich arenes was reported, chelation-assisted meta-C H activation of electron-poor arenes such as benzoic acid derivatives remains a formidable challenge. Herein, we report a general protocol for meta-C-H olefination of benzoic acid derivatives using a nitrile-based sulfonamide template. A broad range of benzoic acid derivatives are meta-selectively olefinated using molecular oxygen as the terminal oxidant. The meta-C-H acetoxylation, product of which is further transformed at the meta-position, is also reported. PMID- 26813920 TI - Impact of the Stem Extract of Thevetia neriifolia on the Feeding Potential and Histological Architecture of the Midgut Epithelial Tissue of Early Fourth Instars of Helicoverpa armigera Hubner. AB - Helicoverpa armigera Hubner is one of the most important agricultural crop pests in the world causing heavy crop yield losses. The continued and indiscriminate use of synthetic insecticides in agriculture for their control has received wide public apprehension because of multifarious problems, including insecticide resistance, resurgence of pest species, environmental pollution, and toxic hazards to humans and nontarget organisms. These problems have necessitated the need to explore and develop alternative strategies using eco-friendly and biodegradable plant products. In view of this, the efficacy of Thevetia neriifolia methanol stem extract was evaluated against the early fourth instars of H. armigera as an antifeedant and stomach poison agent. Feeding of larvae with the diet containing 0.005%-5.0% extract resulted in 2.06%-37.35% antifeedant index; the diet with 5.0% extract caused 54.3% reduced consumption. The negative impact of extract on larval feeding resulted in 37.5%-77.7% starvation, causing adverse effects on the larval weight. Choice between control and experimental diet resulted in feeding preference of larvae for the control diet, leading to 7.3%-42.9% reduced consumption of extract-containing diet. The only exception was the diet with 0.005% extract, which could not cause any deterrence. The midgut histological architecture of H. armigera larvae fed with 0.005%-0.05% extract containing diet with negligible antifeedant potential showed significant damage, shrinkage, and distortion and vacuolization of gut tissues and peritrophic membrane, causing the disintegration of epithelial, goblet, and regenerative cells; the damage increased with the increase in concentration. These changes in the gut caused negative impact on the digestion and absorption of food and thus nutritional deficiency in the larvae, which could probably affect their growth and development. This study reveal the appreciable stomach poison potential of T. neriifolia stem methanol extract against H. armigera larvae, which can be explored as an eco-friendly pest control strategy. PMID- 26813921 TI - Novel research approaches for interstitial cystitis/bladder pain syndrome: thinking beyond the bladder. AB - Despite years of basic and clinical research focused on interstitial cystitis/bladder pain syndrome (IC/BPS), including clinical trials of candidate therapies, there remains an insufficient understanding of underlying cause(s), important clinical features and a lack of effective treatments for this syndrome. Progress has been limited and is likely due to many factors, including a primary focus on the bladder and lower urinary tract as origin of symptoms without adequately considering the potential influence of other local (pelvic) or systemic factors. Traditionally, there has been a lack of sufficiently diverse expertise and application of novel, integrated methods to study this syndrome. However, some important insights have been gained. For example, epidemiological studies have revealed that IC/BPS is commonly associated with other chronic pain conditions, including fibromyalgia, irritable bowel syndrome and chronic fatigue syndrome. These observations suggest that IC/BPS may involve systemic pathophysiology, including alterations of the central nervous system in some patients. Furthermore, there may be multiple causes and contributing factors that manifest in the symptoms of IC/BPS leading to multiple patient sub-groups or phenotypes. Innovative research is necessary to allow for a more complete description of the relationship between this syndrome and other disorders with overlapping symptoms. This report provides examples of such innovative research studies and their findings which have the potential to provide fresh insights into IC/BPS and disorders associated with chronic pain through characterization of broad physiologic systems, as well as assessment of the contribution of the bladder and lower urinary tract. They may also serve as models for future investigation of symptom-based urologic and non-urologic disorders that may remain incompletely characterized by previous, more traditional research approaches. Furthermore, it is anticipated a more holistic understanding of chronic urologic pain and dysfunction will ensue from productive interactions between IC/BPS studies like those described here and broader cutting-edge research endeavors focused on potentially related chronic pain disorders. A more comprehensive vision for IC/BPS inquiry is anticipated to yield new insights into basic disease mechanisms and clinical characteristics that will inform future research studies that will lead to more effective therapies and improved clinical care for these patients. PMID- 26813922 TI - Carbimazole-induced agranulocytosis. AB - A 47 year old lady with hyperthyroidism for past 11/2 years was initially on Carbimazole 20 mg orally then changed to 30 mg (during Hysterectomy) but was taking 10 mg for last 1 year. She had intermittent fever with severe B/L bifrontal headache since 3 weeks. Routine investigations showed anaemia, neutropenia, leucopenia and CRP elevation. Peripheral smear showed normocytic normochromic anaemia with Rouleaux formation, leucopenia with 2% atypical cells and mild thrombocytosis. Widal test, RA factor (Rheumatoid factor) test, Ig M (Immunoglobulin M) dengue, Ig M Lepto, TORCH infections (Toxoplasmosis, Other (Syphilis, varicella-zoster, parvovirus B19), Cytomegalovirus and Herpes infections), ANA (Antinuclear antibody) screen cANCA (Cytoplasmic antineutrophil cytoplasmic antibodies) and pANCA (Perinuclear Anti-Neutrophil Cytoplasmic Antibodies) tests were negative. Bone marrow aspiration showed normo to hypercellular marrow with 15% atypical cells and plasma cells. Multiple myeloma workup was done. Carbimazole was withheld. CONCLUSION: Drug induced agranulocytosis occurs with in 1-2 months of taking the antithyroid medication but onset delayed by 11/2 year. De-challenge resulted normalization of blood parameters. PMID- 26813923 TI - Does Implant Selection Impact Postoperative Complications Following Hip Arthroplasty for Failed Intertrochanteric Fractures? A Retrospective Comparative Study. AB - The purpose of this study is to compare postoperative complications among different acetabular and femoral components of hip arthroplasty for failed intertrochanteric fractures. A total of 79 patients were included and followed-up for an average of 75.6 months (range, 24-244). Fifty-five patients underwent total hip arthroplasty, and 24 had bipolar hemiarthroplasty. Cementless metaphyseal locking, cementless diaphyseal locking, and cemented standard stems were used in 41, 29, and 9 patients, respectively. Dislocation and wear rate were not different between the total hip arthroplasty and bipolar hemiarthroplasty groups. Stem subsidence or loosening was more frequently found in the cementless, metaphyseal locking stem groups. In conclusion, cemented standard stem and cementless diaphyseal locking stem might be better implant choices. With regard to dislocation rate, our results were insufficient to conclude a better implant choice of total hip arthroplasty or bipolar hemiarthroplasty than the other. PMID- 26813924 TI - Amyloid-beta in mitochondrial disease: mutation in a human metallopeptidase links amyloidotic neurodegeneration with mitochondrial processing. PMID- 26813925 TI - Chemotherapy could make breast cancer patients more vulnerable to common infections. PMID- 26813926 TI - ReCAP: ASCO Core Curriculum for Cancer Survivorship Education. AB - CONTEXT AND QUESTIONS ASKED: The number of cancer survivors is increasing exponentially. Currently there about 15 million cancer survivors, and by 2025, there will be nearly 20 million. Who will provide survivorship care, what are evidenced-based or best care practices, what are best methods to disseminate this information and assess its impact on physician practice, and what are the most cost-effective health care delivery models to serve the majority of survivors? SUMMARY ANSWER: The ASCO Survivorship Committee in collaboration with the ASCO Professional Development Committee developed a core curriculum and core competencies for physicians, allied health professionals, training programs, and policymaking organizations. Adapted from Institute of Medicine recommendations for survivorship care, the core curriculum and competencies include the following subheadings: surveillance for recurrence and second malignancies, long-term and late effects, health promotion and prevention, psychosocial well-being, special populations including adolescent and young adult survivors, older adult cancer survivors, caregivers of cancer survivors and communication and care coordination. METHODS: An environmental scan (a process that systematically surveys and interprets relevant data to identify opportunities and barriers) for survivorship was performed. Although survivorship content exists in various courses, conferences, guidelines, and Web-based applications, the information is incomplete and not easily found. Hence, there was a need for this content to be easy to access and available in one place. Content experts formulated the individual sections based on the environmental scan and their knowledge of the various subheadings. BIAS, CONFOUNDING FACTORS, DRAWBACKS: Both an environmental scan and a comprehensive literature review have standard methodologies. The differences are in scope; an environmental scan is more like an overview, and the standard literature review is more granular. For this article, we felt that environmental scan better served the purpose of developing a survivorship core curriculum and competencies. REAL-LIFE IMPLICATIONS: Survivorship care is one the most challenging problems oncologists face today and in the near future. Fundamental to the relatively new field of survivorship care is this core curriculum and competencies, which provide the framework necessary to generate appropriate referrals depending on local practices and expertise. PMID- 26813927 TI - Implementing and Improving Automated Electronic Tumor Molecular Profiling. AB - Oncology practice increasingly requires the use of molecular profiling of tumors to inform the use of targeted therapeutics. However, many oncologists use third party laboratories to perform tumor genomic testing, and these laboratories may not have electronic interfaces with the provider's electronic medical record (EMR) system. The resultant reporting mechanisms, such as plain-paper faxing, can reduce report fidelity, slow down reporting procedures for a physician's practice, and make reports less accessible. Vanderbilt University Medical Center and its genomic laboratory testing partner have collaborated to create an automated electronic reporting system that incorporates genetic testing results directly into the clinical EMR. This system was iteratively tested, and causes of failure were discovered and addressed. Most errors were attributable to data entry or typographical errors that made reports unable to be linked to the correct patient in the EMR. By providing direct feedback to providers, we were able to significantly decrease the rate of transmission errors (from 6.29% to 3.84%; P < .001). The results and lessons of 1 year of using the system and transmitting 832 tumor genomic testing reports are reported. PMID- 26813928 TI - David Oliver: Keeping care home residents out of hospital. PMID- 26813930 TI - Fasiglifam/TAK-875, a Selective GPR40 Agonist, Improves Hyperglycemia in Rats Unresponsive to Sulfonylureas and Acts Additively with Sulfonylureas. AB - Sulfonylureas (SUs) are widely used insulin secretagogues, but they have adverse effects including hypoglycemia and secondary failure. Fasiglifam/TAK-875, a selective GPR40 agonist, enhances glucose-stimulated insulin secretion and improves hyperglycemia. In the present study, we compared the in vivo glucose lowering effects of fasiglifam with SUs. The risk of secondary failure of fasiglifam and the efficacy in rats desensitized to SUs were also evaluated. Moreover, we assessed whether fasiglifam was effective when combined with SUs. In diabetic neonatally streptozotocin-induced rats 1.5 days after birth (N-STZ-1.5), oral administrations of fasiglifam (3-30 mg/kg) dose dependently improved glucose tolerance; the effect was greater than that of glibenclamide at maximal effective doses (glucose AUC: fasiglifam, -37.6%; glibenclamide, -12.3%). Although the glucose-lowering effects of glibenclamide (10 mg/kg/day) were completely diminished in N-STZ-1.5 rats after 4 weeks of treatment, effects were maintained in rats receiving fasiglifam (10 mg/kg/day), even after 15 weeks. Fasiglifam (3 10 mg/kg) was still effective in two models desensitized to SUs: 15-week glibenclamide-treated N-STZ-1.5 rats and aged Zucker diabetic fatty (ZDF) rats. Acute administration of fasiglifam (3 mg/kg) and glimepiride (10 mg/kg) in combination additively decreased glucose AUC (fasiglifam, -25.3%; glimepiride, 20.0%; combination, -43.1%). Although glimepiride (10 mg/kg) decreased plasma glucose below normal in nonfasted control rats, fasiglifam (3 mg/kg) maintained normoglycemia, and no further exaggeration of hypoglycemia was observed with combination treatment. These results indicate that GPR40 agonists could be more effective and durable than SUs. Our results also provide new insights into GPR40 pharmacology and rationale for the use of GPR40 agonists in diabetic patients with SU failure. PMID- 26813931 TI - WHO urged to define responsibility during emergencies. PMID- 26813929 TI - Rigid Adenine Nucleoside Derivatives as Novel Modulators of the Human Sodium Symporters for Dopamine and Norepinephrine. AB - Thirty-two congeneric rigid adenine nucleoside derivatives containing a North (N) methanocarba ribose substitution and a 2-arylethynyl group either enhanced (up to 760% of control) or inhibited [(125)I] methyl (1R,2S,3S)-3-(4-iodophenyl)-8 methyl-8-azabicyclo[3.2.1]octane-2-carboxylate (RTI-55) binding at the human dopamine (DA) transporter (DAT) and inhibited DA uptake. Several nucleosides also enhanced [(3)H]mazindol [(+/-)-5-(4-chlorophenyl)-3,5-dihydro-2H-imidazo[2,1 a]isoindol-5-ol] binding to the DAT. The combination of binding enhancement and functional inhibition suggests possible allosteric interaction with the tropanes. The structure-activity relationship of this novel class of DAT ligands was explored: small N(6)-substition (methyl or ethyl) was favored, while the N1 of the adenine ring was essential. Effective terminal aryl groups include thien-2-yl (compounds 9 and 16), with EC50 values of 35.1 and 9.1 nM, respectively, in [(125)I]RTI-55 binding enhancement, and 3,4-difluorophenyl as in the most potent DA uptake inhibitor (compound 6) with an IC50 value of 92 nM (3-fold more potent than cocaine), but not nitrogen heterocycles. Several compounds inhibited or enhanced binding at the norepinephrine transporter (NET) and serotonin transporter (SERT) and inhibited function in the micromolar range; truncation at the 4'-position in compound 23 allowed for weak inhibition of the SERT. We have not yet eliminated adenosine receptor affinity from this class of DAT modulators, but we identified modifications that remove DAT inhibition as an off-target effect of potent adenosine receptor agonists. Thus, we have identified a new class of allosteric DAT ligands, rigidified adenosine derivatives, and explored their initial structural requirements. They display a very atypical pharmacological profile, i.e., either enhancement by increasing affinity or inhibition of radioligand binding at the DAT, and in some cases the NET and SERT, and inhibition of neurotransmitter uptake. PMID- 26813932 TI - Rise in deaths of mental health patients needs investigating, says MP. PMID- 26813933 TI - Planned Parenthood "sting" film makers are indicted in Texas. PMID- 26813934 TI - Toward disease modification in multiple system atrophy: Pitfalls, bottlenecks, and possible remedies. AB - Multiple system atrophy has recently attracted increased attention in basic and clinical research. Understanding of key pathophysiological mechanismshas improved; and, in the past decade, the first clinical trials aiming at diseasemodification were conducted. However, there is still no established interventional therapy available. In this review, the authors summarize recent advances, discuss bottlenecks and possible pitfalls of previous interventional studies, and suggest future research avenues. PMID- 26813936 TI - Ovarian cancer: Multimodal screening - keeping mortality at bay? PMID- 26813937 TI - Haematological cancer: Good omens - SIRIUS's glow is auspicious for daratumumab. PMID- 26813935 TI - Squamous-cell carcinoma of the anus: progress in radiotherapy treatment. AB - Chemoradiotherapy is the standard-of-care treatment of squamous-cell carcinoma of the anus (SCCA), and this has not changed in decades. Radiation doses of 50-60 Gy, as used in many phase III trials, result in substantial late morbidities and fail to control larger and node-positive tumours. Technological advances in radiation therapy are improving patient outcomes and quality of life, and should be applied to patients with SCCA. Modern techniques such as intensity-modulated radiotherapy (IMRT), rotational IMRT, image-guided radiotherapy using cone-beam CT, and stereotactic techniques have enabled smaller margins and highly conformal plans, resulting in decreased radiation doses to the organs at risk and ensuring a shorter overall treatment time. In this Perspectives article, the use of novel approaches to target delineation, optimized radiotherapy techniques, adaptive radiotherapy, dose-escalation with external-beam radiotherapy (EBRT) or brachytherapy, and the potential for modified fractionation are discussed in the context of SCCA. PMID- 26813938 TI - Bilateral Multiple Variations in Carotid Arteries-A Case Report. AB - The common carotid arteries are the largest bilateral arteries of the head and neck. The common carotid arteries may bifurcate higher or lower than the usual levels. A higher bifurcation is more common. Tortuous arteries if present may be asymptomatic if it is mild but may lead to ischaemia of the organs if severe. The cause could be genetic, or may be thickening of the arteries. During routine dissection of an adult male cadaver in the department of Anatomy, BLDEU's Shri BM Patil Medical college, Vijaypur, we found the bilateral multiple variations in the carotid arteries regarding the bifurcation level of common carotid arteries, tortuous external and internal carotid arteries and the number of branches arising from external carotid arteries. The knowledge of such variations of carotid arteries is of great importance in radiological examinations especially per cutaneous carotid angiography. It is necessary to understand the anatomy of these vessels and its variations to carry out surgeries with minimum complications. PMID- 26813939 TI - Maternal obesity during pregnancy is negatively associated with maternal and neonatal iron status. AB - BACKGROUND/OBJECTIVES: Obesity among pregnant women may adversely affect both maternal iron status throughout pregnancy and placental transfer of iron. The objective of this study was to determine the association of maternal body mass index (BMI) with (1) maternal iron status and inflammation in mid and late pregnancy, (2) the change in maternal iron status throughout pregnancy and (3) neonatal iron status. SUBJECTS/METHODS: We examined longitudinal data from 1613 participants in a pregnancy iron supplementation trial in rural China. Women with uncomplicated singleton pregnancies were enrolled in the early second trimester of pregnancy and followed through parturition. Maternal blood samples obtained at enrollment and in the third trimester and cord blood samples were analyzed for a range of hematological and iron biomarkers. RESULTS: There was a negative association between maternal BMI and iron status at enrollment (transferrin receptor (sTfR): r=0.20, P<0.001; body iron (BI): r=-0.05; P=0.03). This association was markedly stronger among obese women. Maternal BMI was positively associated with maternal inflammation (C-reactive protein: r=0.33, P<0.001). In multiple linear regression models, maternal BMI was negatively associated with neonatal iron status (cord serum ferritin: -0.01, P=0.008; BI: -0.06, P=0.006) and associated with a lower decrease in iron status throughout pregnancy (sTfR: 4.6, P<0.001; BI: 1.1, P=0.004). CONCLUSIONS: Maternal obesity during pregnancy may adversely affect both maternal and neonatal iron status, potentially through inflammatory pathways. PMID- 26813940 TI - Maternal pre-pregnancy BMI, gestational weight gain and breastfeeding. AB - BACKGROUND/OBJECTIVES: The aims were to investigate the association of maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with breastfeeding (BF) duration and BF pattern at 3 months of age. SUBJECTS/METHODS: This was a prospective cohort study of 4231 children who were enrolled at birth and were followed-up at 3, 12, 24 and 48 months of age to gather information on maternal and offspring characteristics including BF patterns and BF duration. Maternal pre-pregnancy BMI was categorized according to the WHO classification and GWG according to the 2009 Institute of Medicine recommendations. Cox's proportional hazards model was used to assess whether pre-pregnancy BMI and GWG were associated with BF and exclusive breastfeeding (EBF) duration. Predicted probabilities of BF patterns at 3 months were estimated by multinomial logistic regression. RESULTS: Information on BF was available to 4011 infants. The total BF and EBF median durations were 7.0 months and 1.5 months, respectively. There were no differences in duration of any BF or EBF according to pre-pregnancy BMI or GWG categories. There was an increased predicted probability for weaning before the age of 3 months among infants from obese women, compared with those from mothers with normal pre-pregnancy BMI, with margins adjusted predictions of 0.36 (95% confidence interval (CI) 0.31-0.41) and 0.23 (95% CI 0.21-0.25), respectively. CONCLUSIONS: Infants from pre-pregnancy overweight/obese mothers presented higher probability of early weaning compared with infants from normal weight mothers. Obese/overweight pregnant women need supplementary guidance about BF benefits to infant health during prenatal and postnatal care. PMID- 26813941 TI - A Rare Constellation of Hurthle Cell Thyroid Carcinoma and Parathyroid Carcinoma. AB - Separate occurrence of thyroid and parathyroid carcinoma in patients is extremely rare, and to the best of our knowledge, only 7 patients with documented parathyroid and papillary thyroid carcinomas have been described formerly in published reports. We report a patient with an extremely unusual clinical presentation of Hurthle cell carcinoma in thyroid and parathyroid carcinoma. The patient displayed a rare presentation of life-threatening hypercalcaemia after total para-thyroidectomy and failed to respond to standard therapy. Our review of available literature yielded insufficient evidence in managing such. When a patient with thyroid cancer is diagnosed, checking for serum calcium is advised. This is considered a useful method for detecting possible incidental parathyroid lesion and screening the probable concealed parathyroid pathology. PMID- 26813942 TI - Nanoparticles Based on Chitosan as Carriers for the Combined Herbicides Imazapic and Imazapyr. AB - The use of lower concentrations and fewer applications of herbicides is one of the prime objectives of the sustainable agriculture as it decreases the toxicity to non-targeted organisms and the risk of wider environmental contamination. In the present work, nanoparticles were developed for encapsulation of the herbicides imazapic and imazapyr. Alginate/chitosan and chitosan/tripolyphosphate nanoparticles were manufactured, and their physicochemical stability was evaluated. Determinations were made of the encapsulation efficiency and release kinetics, and the toxicity of the nanoparticles was evaluated using cytotoxicity and genotoxicity assays. The effects of herbicides and herbicide-loaded nanoparticles on soil microorganisms were studied in detail using real-time polymerase chain reactions. The nanoparticles showed an average size of 400 nm and remained stable during 30 days of storage at ambient temperature. Satisfactory encapsulation efficiencies of between 50 and 70% were achieved for both types of particles. Cytotoxicity assays showed that the encapsulated herbicides were less toxic, compared to the free compounds, and genotoxicity was decreased. Analyses of soil microbiota revealed changes in the bacteria of the soils exposed to the different treatments. Our study proves that encapsulation of the herbicides improved their mode of action and reduced their toxicity, indicating their suitability for use in future practical applications. PMID- 26813943 TI - Prominent scapulae mimicking an inherited myopathy expands the phenotype of CHD7 related disease. AB - CHD7 variants are a well-established cause of CHARGE syndrome, a disabling multi system malformation disorder that is often associated with deafness, visual impairment and intellectual disability. Less severe forms of CHD7-related disease are known to exist, but the full spectrum of phenotypes remains uncertain. We identified a de novo missense variant in CHD7 in a family presenting with musculoskeletal abnormalities as the main manifestation of CHD7-related disease, representing a new phenotype. The proband presented with prominent scapulae, mild shoulder girdle weakness and only subtle dysmorphic features. Investigation revealed hypoplasia of the trapezius and sternocleidomastoid muscles and semicircular canal defects, but he did not fulfill diagnostic criteria for CHARGE syndrome. Although the shoulders are often sloping and anteverted in CHARGE syndrome, the underlying neuromuscular cause has never been investigated. This report expands the phenotypes associated with CHD7 mutations to include a musculoskeletal presentation, with hypoplasia of the shoulder and neck muscles. CHD7 should be considered in patients presenting in childhood with stable scapular winging, particularly if accompanied by dysmorphic features and balance difficulties. PMID- 26813945 TI - Clinical utility gene card for: Familial platelet disorder with associated myeloid malignancies. PMID- 26813944 TI - Copy number variation of scavenger-receptor cysteine-rich domains within DMBT1 and Crohn's disease. AB - Previous work has shown that the gene DMBT1, which encodes a large secreted epithelial glycoprotein known as salivary agglutinin, gp340, hensin or muclin, is an innate immune defence protein that binds bacteria. A deletion variant of DMBT1 has been previously associated with Crohn's disease, and a DMBT1(-/-) knockout mouse has increased levels of colitis induced by dextran sulphate. DMBT1 has a complex copy number variable structure, with two, independent, rapidly mutating copy number variable regions, called CNV1 and CNV2. Because the copy number variable regions are predicted to affect the number of bacteria-binding domains, different alleles may alter host-microbe interactions in the gut. Our aim was to investigate the role of this complex variation in susceptibility to Crohn's disease by assessing the previously reported association. We analysed the association of both copy number variable regions with presence of Crohn's disease, and its severity, on three case-control cohorts. We also reanalysed array comparative genomic hybridisation data (aCGH) from a large case-control cohort study for both copy number variable regions. We found no association with a linear increase in copy number, nor when the CNV1 is regarded as presence or absence of a deletion allele. Taken together, we show that the DMBT1 CNV does not affect susceptibility to Crohn's disease, at least in Northern Europeans. PMID- 26813946 TI - Against all odds: blended phenotypes of three single-gene defects. AB - Whole-exome sequencing allows for an unbiased and comprehensive mutation screening. Although successfully used to facilitate the diagnosis of single-gene disorders, the genetic cause(s) of a substantial proportion of presumed monogenic diseases remain to be identified. We used whole-exome sequencing to examine offspring from a consanguineous marriage featuring a novel combination of congenital hypothyroidism, hypomagnesemia and hypercholesterolemia. Rather than identifying one causative variant, we report the first instance in which three independent autosomal-recessive single-gene disorders were identified in one patient. Together, the causal variants give rise to a blended and seemingly novel phenotype: we experimentally characterized a novel splice variant in the thyroglobulin gene (c.638+5G>A), resulting in skipping of exon 5, and detected a pathogenic splice variant in the magnesium transporter gene TRPM6 (c.2667+1G>A), causing familial hypomagnesemia. Based on the third variant, a stop variant in ABCG5 (p.(Arg446*)), we established a diagnosis of sitosterolemia, confirmed by elevated blood plant sterol levels and successfully initiated targeted lipid lowering treatment. We propose that blended phenotypes resulting from several concomitant single-gene disorders in the same patient likely account for a proportion of presumed monogenic disorders of currently unknown cause and contribute to variable genotype-phenotype correlations. PMID- 26813947 TI - Variants of the ACTG2 gene correlate with degree of severity and presence of megacystis in chronic intestinal pseudo-obstruction. AB - Chronic intestinal pseudo-obstruction (CIPO) syndromes are heterogeneous gastrointestinal disorders, caused by either neuropathy or myopathy, resulting in compromised peristalsis and intestinal obstruction. CIPO can have a profound impact on quality of life, leading the most severely affected individuals to life long parenteral nutrition and urinary catheterization. To search for disease causing gene(s), we performed the whole exome sequencing (WES) in both eight sporadic and two familial cases, followed by targeted sequencing in additional CIPO patients. After identifying a heterozygous missense variant in the ACTG2 gene in one of 10 patients undergone WES, targeted Sanger sequencing of this gene allowed to detect heterozygous missense variants in 9 of 23 further patients with either megacystis-microcolon-intestinal hypoperistalsis syndrome or intestinal pseudo-obstruction. Variants thus identified, one of which still unreported, affect highly conserved regions of the ACTG2 gene that encodes a protein crucial for correct enteric muscle contraction. These findings provided evidence for a correlation between the clinical phenotype and genotype at the ACTG2 locus, a first step to improve the diagnosis and prognosis of these severe conditions. PMID- 26813950 TI - Prostate cancer: Testosterone-guided ADT for prostate cancer. PMID- 26813951 TI - Prostate cancer: MCT4 is a novel target for prostate cancer. PMID- 26813954 TI - Kidney cancer: When worlds collide--integrating metabolic and transcriptomic data in ccRCC. PMID- 26813956 TI - Prostate cancer: A prognostic pathway signature for personalizing therapy. PMID- 26813955 TI - Active surveillance for prostate cancer: a narrative review of clinical guidelines. AB - In the past decade active surveillance (AS) of men with localized prostate cancer has become an increasingly popular management option, and a range of clinical guidelines have been published on this topic. Existing guidelines regarding AS for prostate cancer vary widely, but predominantly state that the most suitable patients for AS are those with pretreatment clinical stage T1c or T2 tumours, serum PSA levels <10 ng/ml, biopsy Gleason scores of 6 or less, a maximum of one or two tumour-positive biopsy core samples and/or a maximum of 50% of cancer per core sample. Following initiation of an AS programme, most guidelines recommend serial serum PSA measurements, digital rectal examinations and surveillance biopsies to check for and identify pathological indications of tumour progression. Definitions of disease reclassification and progression differ among guidelines and multiple criteria for initiation of definitive treatment are proposed. The variety of descriptions of criteria for clinically insignificant prostate cancer indicates a lack of consensus on optimal AS and intervention thresholds. A single set of guidelines are needed in order to reduce variations in clinical practice and to optimize clinical decision-making. To enable truly evidence-based guidelines, further research that combines existing evidence, while also gathering information from more long-term studies is needed. PMID- 26813957 TI - Need of Revision of Lower Limb Amputations in a North Indian Tertiary Care Centre. AB - INRTODUCTION: Amputation of the extremity is a big challenge to mankind. Revision rate of primary amputations stands high despite of maximum care at tertiary care centres. The purpose of this study was to establish cause for the revision, identify preventable cause and to assess outcome of revision amputation surgery. MATERIALS AND METHODS: We performed a retrospective study on lower limb revision amputations in Department of Physical Medicine and Rehabilitation and Department of Orthopaedic Surgery, King George Medical University between Jan 2012 to Jan 2015. All patients of any age group and gender admitted for revision amputation were included in the study population. RESULTS: A total of 32 patients who required revision amputation of lower limbs was included in the study, out of these 62.50 % were male and 37.50 % were female. Age of the patients ranged from 5 to 72 years with mean of 42 years. Most common level of initial amputation was below knee (56.25 %) followed by above knee amputation (31.25%). Most common indication for initial amputation was trauma (43.75%) followed by infection, vascular diseases, malignancy and leprosy. Poor stump formation was found to be most common indication for revision amputation (37.50%) followed by infection (25%), recurrent ulceration (18.75%), stitch abscess (6.25%), neuroma (6.25%), and necrosis (6.25%). All patients were treated successfully. CONCLUSION: Revision amputation increases morbidity. Poor stump formation at the time of initial amputation and infection are the most common indication for revision surgery. These are the preventable causes and every effort should be made to alleviate these as well as other preventable causes. PMID- 26813959 TI - Generation of 2,000 breast cancer metabolic landscapes reveals a poor prognosis group with active serotonin production. AB - A major roadblock in the effective treatment of cancers is their heterogeneity, whereby multiple molecular landscapes are classified as a single disease. To explore the contribution of cellular metabolism to cancer heterogeneity, we analyse the Metabric dataset, a landmark genomic and transcriptomic study of 2,000 individual breast tumours, in the context of the human genome-scale metabolic network. We create personalized metabolic landscapes for each tumour by exploring sets of active reactions that satisfy constraints derived from human biochemistry and maximize congruency with the Metabric transcriptome data. Classification of the personalized landscapes derived from 997 tumour samples within the Metabric discovery dataset reveals a novel poor prognosis cluster, reproducible in the 995-sample validation dataset. We experimentally follow mechanistic hypotheses resulting from the computational study and establish that active serotonin production is a major metabolic feature of the poor prognosis group. These data support the reconsideration of concomitant serotonin-specific uptake inhibitors treatment during breast cancer chemotherapy. PMID- 26813958 TI - Waist-to-height ratio as a measure of abdominal obesity in southern Chinese and European children and adolescents. AB - BACKGROUND: Waist-to-height ratio (WHtR), with a 0.5 threshold (WHtR0.5), is regarded as a simple age- and gender-independent criterion of abdominal obesity (AO) and a better predictor than the 90th percentile of waist circumference (WCP90). OBJECTIVE: An analysis of gender and ethnic differences of WHtR and other AO indices between children and adolescents from southern China (HK: Hong Kong, China) and Europe (LD: Lodz, Poland). SUBJECTS: Two large cross-sectional surveys of children and adolescents aged 7-19 years, one from LD (13 172) and one from HK (14 566). METHODS: The percentile and standardized values of WHtR and other parameters (WC, body mass index (BMI)) were assessed using the LMS method. The WHtR values corresponding to WCP90 and to the BMI definition of global obesity (BMIP95) were evaluated with the polynomial regression model. The compliance of the AO prevalence data, obtained with two criteria (WCP90 vs WHtR0.5) was analyzed using Cohen's kappa index (kappaC). RESULTS: The WHtR data of Polish subjects were generally higher than those of their HK peers, and the ethic differences increased with age. The WHtR values of HK boys showed a stronger relationship with BMI z-score. WHtR corresponding to WCP90 assumed values <0.5. An application of Cohen's kappa coefficient (kappaC) to Polish subjects showed either 'substantial' (kappaC>0.6) or 'almost perfect' (kappaC>0.8) agreement in the AO prevalence for both criteria (WCP90 and WHtR0.5). For these criteria, either 'fair' (kappaC <0.4) or 'moderate' (kappaC<0.6) AO consistency ratings were observed among HK girls. In HK boys, a significant difference in the prevalence of AO was observed, independent of the criterion used. CONCLUSIONS: Our results provide further evidence of the need for developing ethnic-specific WC charts and for recommending that a WHtR cutoff of 0.5 may not be appropriate to predict cardiometabolic risk in children of different ethnic groups. PMID- 26813960 TI - A novel method for evaluating antibody-dependent cell-mediated cytotoxicity by flowcytometry using cryopreserved human peripheral blood mononuclear cells. AB - Analyzing the cytotoxic functions of effector cells, such as NK cells against target cancer cells, is thought to be necessary for predicting the clinical efficacy of antibody-dependent cellular cytotoxicity (ADCC) -dependent antibody therapy. The (51)Cr release assay has long been the most widely used method for quantification of ADCC activity. However, the reproducibilities of these release assays are not adequate, and they do not allow evaluation of the lysis susceptibilities of distinct cell types within the target cell population. In this study, we established a novel method for evaluating cytotoxicity, which involves the detection and quantification of dead target cells using flowcytometry. CFSE (carboxyfluorescein succinimidyl ester) was used as a dye to specifically stain and thereby label the target cell population, allowing living and dead cells, as well as both target and effector cells, to be quantitatively distinguished. Furthermore, with our new approach, ADCC activity was more reproducibly, sensitively, and specifically detectable, not only in freshly isolated but also in frozen human peripheral blood mononuclear cells (PBMCs), than with the calcein-AM release assay. This assay, validated herein, is expected to become a standard assay for evaluating ADCC activity which will ultimately contribute the clinical development of ADCC dependent-antibody therapies. PMID- 26813961 TI - Cutaneous-type pemphigus vulgaris successfully treated with topical corticosteroids. PMID- 26813962 TI - Red Cell Alloimmunization to Rhesus Antigen Among Pregnant Women Attending a Tertiary Care Hospital in Oman. AB - OBJECTIVES: The detection of maternal alloimmunization against red cell antigens is vital in the management of hemolytic disease of the fetus and newborn. We sought to measure the presence of allosensitization to Rhesus D (RhD) antibodies in antenatal women attending a tertiary care hospital and assess the fetal outcome in sensitized women. ? METHODS: We conducted a retrospective review of pregnant Omani women who registered at the Sultan Qaboos University Hospital between June 2011 and June 2013. Pregnant women were tested for ABO blood type and were screened for RhD antigen and antibodies at their first antenatal clinic visit. In women who tested positive for the RhD antibodies, an antibody titer was performed to evaluate the severity of their case. RESULTS: Data was available on 1,251 pregnant women who were managed and delivered at Sultan Qaboos University Hospital. The prevalence of RhD negative pregnant women was 7.3%. Blood group O was the most common followed by A, B, and AB. The rate of RhD negative alloimmunization was 10%, and anti-D was the most common antibody detected. There were no stillbirths or neonatal deaths. Postnatal transfusion was necessary for only one baby. CONCLUSIONS: The prevalence of RhD negativity was comparable to other Asian countries. Previous RhD alloimmunization and history of miscarriages were the most common maternal medical history. PMID- 26813963 TI - Newly diagnosed lung cancer patients' preferences for and beliefs about physical activity prior to chemotherapy. AB - Physical activity has been found to have a number of benefits for lung cancer patients yet very little information is available concerning physical activity beliefs and preferences for this population. The purpose of the study was to explore physical activity programming and counseling preferences and beliefs about physical activity in newly diagnosed lung cancer patients scheduled to receive chemotherapy. A total of 43 new diagnosed lung cancer patients completed a researcher-administered survey prior to commencing chemotherapy. Results indicated that only 7 participants (17%) reported meeting public health recommendations for physical activity yet the majority of participants (n = 28) indicated interest or possible interest in physical activity counseling. Many participants also indicated interest or possible interest in an exercise program (n = 29) for lung cancer survivors, preferring it to start during chemotherapy (n = 20), for it to be home based (n = 21), and moderate in intensity (n = 22). The most common behavioral belief (advantage) of physical activity was to build/maintain strength (n = 26) and the most common control belief (barrier) was fatigue (n = 11). These data suggest that physical activity counseling and programming may be well received by newly diagnosed lung cancer patients. Information about physical activity and programming preferences and beliefs from this study may be useful for the design of optimal physical activity interventions for lung cancer patients. PMID- 26813964 TI - PPARgamma Represses Apolipoprotein A-I Gene but Impedes TNFalpha-Mediated ApoA-I Downregulation in HepG2 Cells. AB - Apolipoprotein A-I (ApoA-I) is the main anti-atherogenic component of human high density lipoproteins (HDL). ApoA-I gene expression is regulated by several nuclear receptors, which are the sensors for metabolic changes during development of cardiovascular diseases. Activation of nuclear receptor PPARgamma has been shown to impact lipid metabolism as well as inflammation. Here, we have shown that synthetic PPARgamma agonist GW1929 decreases both ApoA-I mRNA and protein levels in HepG2 cells and the effect of GW1929 on apoA-I gene transcription depends on PPARgamma. PPARgamma binds to the sites A and C within the hepatic enhancer of apoA-I gene and the negative regulation of apoA-I gene transcription by PPARgamma appears to be realized via the site C (-134 to -119). Ligand activation of PPARgamma leads to an increase of LXRbeta and a decrease of PPARalpha binding to the apoA-I gene hepatic enhancer in HepG2 cells. GW1929 abolishes the TNFalpha-mediated decrease of ApoA-I mRNA expression in both HepG2 and Caco-2 cells but does not block TNFalpha-mediated inhibition of ApoA-I protein secretion by HepG2 cells. These data demonstrate that complex of PPARgamma with GW1929 is a negative regulator involved in the control of ApoA-I expression and secretion in human hepatocyte- and enterocyte-like cells. J. Cell. Biochem. 117: 2010-2022, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26813965 TI - A Computational Protein Phenotype Prediction Approach to Analyze the Deleterious Mutations of Human MED12 Gene. AB - Genetic mutations in MED12, a subunit of Mediator complex are seen in a broad spectrum of human diseases. However, the underlying basis of how these pathogenic mutations elicit protein phenotype changes in terms of 3D structure, stability and protein binding sites remains unknown. Therefore, we aimed to investigate the structural and functional impacts of MED12 mutations, using computational methods as an alternate to traditional in vivo and in vitro approaches. The MED12 gene mutations details and their corresponding clinical associations were collected from different databases and by text-mining. Initially, diverse computational approaches were applied to categorize the different classes of mutations based on their deleterious impact to MED12. Then, protein structures for wild and mutant types built by integrative modeling were analyzed for structural divergence, solvent accessibility, stability, and functional interaction deformities. Finally, this study was able to identify that genetic mutations mapped to exon-2 region, highly conserved LCEWAV and Catenin domains induce biochemically severe amino acid changes which alters the protein phenotype as well as the stability of MED12-CYCC interactions. To better understand the deleterious nature of FS-IDs and Indels, this study asserts the utility of computational screening based on their propensity towards non-sense mediated decay. Current study findings may help to narrow down the number of MED12 mutations to be screened for mediator complex dysfunction associated genetic diseases. This study supports computational methods as a primary filter to verify the plausible impact of pathogenic mutations based on the perspective of evolution, expression and phenotype of proteins. J. Cell. Biochem. 117: 2023-2035, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26813966 TI - Antifungal Resistance and Virulence Among Candida spp. from Captive Amazonian manatees and West Indian Manatees: Potential Impacts on Animal and Environmental Health. AB - This work aimed at evaluating the antifungal susceptibility and production of virulence factors by Candida spp. isolated from sirenians in Brazil. The isolates (n = 105) were recovered from the natural cavities of Amazonian and West Indian manatees and were tested for the susceptibility to amphotericin B, itraconazole, and fluconazole and for the production of phospholipases, proteases, and biofilm. The minimum inhibitory concentrations (MICs) for amphotericin B ranged from 0.03 to 1 ug/mL, and no resistant isolates were detected. Itraconazole and fluconazole MICs ranged from 0.03 to 16 ug/mL and from 0.125 to 64 ug/mL, respectively, and 35.2% (37/105) of the isolates were resistant to at least one of these azole drugs. Concerning the production of virulence factors, phospholipase activity was observed in 67.6% (71/105) of the isolates, while protease activity and biofilm production were detected in 50.5% (53/105) and 32.4% (34/105) of the isolates, respectively. Since the natural cavities of manatees are colonized by resistant and virulent strains of Candida spp., these animals can act as sources of resistance and virulence genes for the environment, conspecifics and other animal species, demonstrating the potential environmental impacts associated with their release back into their natural habitat. PMID- 26813967 TI - Nakamurella endophytica sp. nov., a novel endophytic actinobacterium isolated from the bark of Kandelia candel. AB - A Gram-stain-positive, aerobic, coccus-shaped, non-spore-forming actinobacterium, designated strain 2Q3S-4-2T, was isolated from the surface-sterilized bark of Kandelia candel, collected from Cotai Ecological Zones in Macao, PR China. It was tested using a polyphasic approach to determine its taxonomic position. Strain 2Q3S-4-2T grew optimally without NaCl at 28-30 degrees C and at pH 7.0. Substrate mycelia and aerial mycelia were not formed and no diffusible pigments were observed on the media tested. Phylogenetic analysis, based on 16S rRNA gene sequences, suggested that strain 2Q3S-4-2T belonged to the genus Nakamurella, sharing highest 16S rRNA gene sequence similarity with Nakamurella flavida DS-52T (96.76 %). The DNA G+C content of strain 2Q3S-4-2T was 67.8 mol%. The cell-wall peptidoglycan contained meso-diaminopimelic acid and MK-8(H4) was the predominant menaquinone. The predominant polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, unidentified aminophospholipids and phosphatidylinositol. The major fatty acids were iso-C16 : 0, anteiso-C15 : 0, anteiso-C17 : 0 and C16 : 0. On the basis of the phylogenetic, phenotypic and chemotaxonomic analysis, strain 2Q3S-4-2T represents a novel species of the genus Nakamurella, for which the name Nakamurella endophytica sp. nov. is proposed. The type strain is 2Q3S-4-2T ( = DSM 100722T = CGMCC 4.7308T). PMID- 26813968 TI - Bereavement by suicide as a risk factor for suicide attempt: a cross-sectional national UK-wide study of 3432 young bereaved adults. AB - OBJECTIVES: US and UK suicide prevention strategies suggest that bereavement by the suicide of a relative or friend is a risk factor for suicide. However, evidence is lacking that the risk exceeds that of any sudden bereavement, is specific to suicide, or applies to peer suicide. We conducted the first controlled UK-wide study to test the hypothesis that young adults bereaved by suicide have an increased risk of suicidal ideation and suicide attempt compared with young adults bereaved by other sudden deaths. DESIGN: National cross sectional study. SETTING: Staff and students at 37 UK higher educational institutions in 2010. PARTICIPANTS: 3432 eligible respondents aged 18-40 exposed to sudden bereavement of a friend or relative after the age of 10. EXPOSURES: Bereavement by suicide (n=614), by sudden unnatural causes (n=712) and by sudden natural causes (n=2106). PRIMARY OUTCOME MEASURES: Incident suicidal ideation and suicide attempt. FINDINGS: Adults bereaved by suicide had a higher probability of attempting suicide (adjusted OR (AOR)=1.65; 95% CI 1.12 to 2.42; p=0.012) than those bereaved by sudden natural causes. There was no such increased risk in adults bereaved by sudden unnatural causes. There were no group differences in probability of suicidal ideation. The effect of suicide bereavement was similar whether bereaved participants were blood-related to the deceased or not. The significant association between bereavement by suicide and suicide attempt became non-significant when adding perceived stigma (AOR=1.11; 95% CI 0.74 to 1.67; p=0.610). When compared with adults bereaved by sudden unnatural causes, those bereaved by suicide did not show significant differences in suicide attempt (AOR=1.48; 95% CI 0.94 to 2.33; p=0.089). CONCLUSIONS: Bereavement by suicide is a specific risk factor for suicide attempt among young bereaved adults, whether related to the deceased or not. Suicide risk assessment of young adults should involve screening for a history of suicide in blood relatives, non-blood relatives and friends. PMID- 26813970 TI - Serum Glycans as Risk Markers for Non-Small Cell Lung Cancer. AB - Previous studies have suggested occurrence of altered serum glycan profiles in patients with lung cancer. Here, we aimed to determine the predictive value of serum glycans to distinguish non-small cell lung cancer (NSCLC) cases from controls in prediagnostic samples using a previously validated predictive protein marker pro-SFTPB, as anchor. Blinded prediagnostic serum samples were obtained from the Carotene and Retinol Efficacy Trial (CARET), and included a discovery set of 100 NSCLC cases and 199 healthy controls. A second test set consisted of 108 cases and 216 controls. Cases and controls were matched for age at baseline (5-year groups), sex, smoking status (current vs. former), study enrollment cohort, and date of blood draw. Serum glycan profiles were determined by mass spectrometry. Twelve glycan variables were identified to have significant discriminatory power between cases and controls in the discovery set (AUC > 0.6). Of these, four were confirmed in the independent validation set. A combination marker yielded AUCs of 0.74 and 0.64 in the discovery and test set, respectively. Four glycan variables exhibited significant incremental value when combined with pro-SFTPB compared with pro-SFTPB alone with AUCs of 0.73, 0.72, 0.72, and 0.72 in the test set, indicating that serum glycan signatures have relevance to risk assessment for NSCLC. PMID- 26813971 TI - Premalignancy in Prostate Cancer: Rethinking What we Know. AB - High-grade prostatic intraepithelial neoplasia (PIN) has been accepted as the main precursor lesion to invasive adenocarcinoma of the prostate, and this is likely to be the case. However, in an unknown number of cases, lesions fulfilling the diagnostic criteria for high-grade PIN may actually represent intra-acinar or intraductal spread of invasive carcinoma. Intriguingly, this possibility would not contradict many of the findings of previous epidemiologic studies linking high-grade PIN to carcinoma or molecular pathologic studies showing similar genomic (e.g., TMPRSS2-ERG gene fusion) as well as epigenomic and molecular phenotypic alterations between high-grade PIN and carcinoma. Also, this possibility would be consistent with previous anatomic studies in prostate specimens linking high-grade PIN and carcinoma in autopsy and other whole prostate specimens. In addition, if some cases meeting morphologic criteria for PIN actually represent intra-acinar spread of invasive carcinoma, this could be an important potential confounder of the interpretation of past clinical trials enrolling patients presumed to be without carcinoma, who are at high risk of invasive carcinoma. Thus, in order to reduce possible bias in future study/trial designs, novel molecular pathology approaches are needed to decipher when an apparent PIN lesion may be intra-acinar/intra-ductal spread of an invasive cancer and when it truly represents a precursor state. Similar approaches are needed for lesions known as intraductal carcinoma to facilitate better classification of them as true intra-ductal/acinar spread on one hand or as precursor high-grade PIN (cribriform type) on the other hand; a number of such molecular approaches (e.g., coevaluating TMPRSS-ERG fusion and PTEN loss) are already showing excellent promise. Cancer Prev Res; 9(8); 648-56. (c)2016 AACR. PMID- 26813969 TI - Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer's disease. AB - Alzheimer's disease is a multifactorial dementia disorder characterized by early amyloid-beta, tau deposition, glial activation and neurodegeneration, where the interrelationships between the different pathophysiological events are not yet well characterized. In this study, longitudinal multitracer positron emission tomography imaging of individuals with autosomal dominant or sporadic Alzheimer's disease was used to quantify the changes in regional distribution of brain astrocytosis (tracer (11)C-deuterium-L-deprenyl), fibrillar amyloid-beta plaque deposition ((11)C-Pittsburgh compound B), and glucose metabolism ((18)F fluorodeoxyglucose) from early presymptomatic stages over an extended period to clinical symptoms. The 52 baseline participants comprised autosomal dominant Alzheimer's disease mutation carriers (n = 11; 49.6 +/- 10.3 years old) and non carriers (n = 16; 51.1 +/- 14.2 years old; 10 male), and patients with sporadic mild cognitive impairment (n = 17; 61.9 +/- 6.4 years old; nine male) and sporadic Alzheimer's disease (n = 8; 63.0 +/- 6.5 years old; five male); for confidentiality reasons, the gender of mutation carriers is not revealed. The autosomal dominant Alzheimer's disease participants belonged to families with known mutations in either presenilin 1 (PSEN1) or amyloid precursor protein (APPswe or APParc) genes. Sporadic mild cognitive impairment patients were further divided into (11)C-Pittsburgh compound B-positive (n = 13; 62.0 +/- 6.4; seven male) and (11)C-Pittsburgh compound B-negative (n = 4; 61.8 +/- 7.5 years old; two male) groups using a neocortical standardized uptake value ratio cut-off value of 1.41, which was calculated with respect to the cerebellar grey matter. All baseline participants underwent multitracer positron emission tomography scans, cerebrospinal fluid biomarker analysis and neuropsychological assessment. Twenty-six of the participants underwent clinical and imaging follow-up examinations after 2.8 +/- 0.6 years. By using linear mixed-effects models, fibrillar amyloid-beta plaque deposition was first observed in the striatum of presymptomatic autosomal dominant Alzheimer's disease carriers from 17 years before expected symptom onset; at about the same time, astrocytosis was significantly elevated and then steadily declined. Diverging from the astrocytosis pattern, amyloid-beta plaque deposition increased with disease progression. Glucose metabolism steadily declined from 10 years after initial amyloid-beta plaque deposition. Patients with sporadic mild cognitive impairment who were (11)C-Pittsburgh compound B-positive at baseline showed increasing amyloid-beta plaque deposition and decreasing glucose metabolism but, in contrast to autosomal dominant Alzheimer's disease carriers, there was no significant longitudinal decline in astrocytosis over time. The prominent initially high and then declining astrocytosis in autosomal dominant Alzheimer's disease carriers, contrasting with the increasing amyloid-beta plaque load during disease progression, suggests astrocyte activation is implicated in the early stages of Alzheimer's disease pathology. PMID- 26813972 TI - Type 2 Diabetes Mellitus in Saudi Arabia: Major Challenges and Possible Solutions. AB - The World Health Organization has ranked Saudi Arabia as having the second highest rate of diabetes in the Middle East (7th highest in the world) with an estimated population of 7 million living with diabetes and more than 3 million with pre-diabetes. This presents a pressing public health problem. Several challenges in diabetes management need to be tackled in Saudi Arabia, including the growing prevalence (chiefly among children and young adults), micro-and macrovascular complications, lifestyle changes, late diagnosis, poor awareness and high treatment costs. Over the last two decades, the Saudi population saw an increase in the expenses in healthcare and treatment of diabetes by more than 500%. In 2014, the health care budget was 180 billion (Saudi Riyal) of which 17 billion was spent on all Saudis, with an approximate 25 billion on the entire Saudi diabetic population. This implies that the direct expense of diabetes is costing Saudi Arabia around 13.9% of the total health expenditure. Therefore, unless a comprehensive epidemic control program/ multidisciplinary approach is stringently enforced, the diabetes mellitus burden on Saudi Arabia will probably increase to very serious levels. It is crucial to implement improved health and health-related quality of life of to those with diabetes, thus minimizing the social and personal expenses for diabetes care in Saudi Arabia. In this study we discuss the significant and major threats posed by diabetes mellitus to the Saudi population and recommend essential possible solutions to delay/ prevent this formidable issue. PMID- 26813973 TI - Modulation of leukotriene B4 receptor 1 signaling by receptor for advanced glycation end products (RAGE). AB - Leukotriene B4 (LTB4) receptor 1 (BLT1), a high-affinity GPCR for LTB4, plays important roles in acute and chronic inflammatory diseases. Although the LTB4 BLT1 axis is known to promote inflammation, no studies have defined the binding proteins that modulate LTB4-BLT1 signaling. In this study, the receptor for advanced glycation end products (RAGE) interacted with BLT1 in human cervical epithelial HeLa cells. RAGE increased LTB4-BLT1-dependent ERK phosphorylation and inhibited LTB4-BLT1-dependent activation of NF-kappaB and up-regulation of proinflammatory cytokines and chemokines. RAGE-dependent inhibition of NF-kappaB was blunted by treatment with an MEK inhibitor, suggesting that RAGE suppresses LTB4-BLT1-dependent NF-kappaB signaling by enhancing the MEK-ERK pathway. Meanwhile, in a chemotaxis assay of mouse bone marrow-derived neutrophils, the velocity of LTB4-dependent neutrophil migration was attenuated by soluble RAGE, which is an inhibitory decoy protein for RAGE signaling, in a dose-dependent manner (0.2-5 MUg/ml), or by RAGE deficiency. Furthermore, both LTB4-dependent ERK phosphorylation in neutrophils and LTB4-dependent neutrophil accumulation in a murine peritonitis model were significantly attenuated in RAGE-deficient mice compared with C57BL/6J wild-type mice, indicating that RAGE potentiates LTB4 dependent neutrophil migration by enhancing ERK phosphorylation. Our results demonstrate that RAGE interacts with BLT1 and modulates LTB4-BLT1 signaling through potentiation of the MEK-ERK pathway.-Ichiki, T., Koga, T., Okuno, T., Saeki K., Yamamoto, Y., Yamamoto, H., Sakaguchi, M., Yokomizo, T. Modulation of leukotriene B4 receptor 1 signaling by receptor for advanced glycation end products (RAGE). PMID- 26813974 TI - Diet-induced obesity in mice diminishes hematopoietic stem and progenitor cells in the bone marrow. AB - Obesity is associated with chronic low-grade inflammation, characterized by leukocytosis and inflammation in the adipose tissue. Continuous activation of the immune system is a stressor for hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM). Here we studied how diet-induced obesity (DIO) affects HSPC population dynamics in the BM. Eight groups of age-matched C57Bl/6 mice received a high-fat diet (45% kilocalories from fat) ranging from 1 d up to 18 wk. The obesogenic diet caused decreased proliferation of lineage(-)Sca-1(+)c Kit(+) (LSK) cells in the BM and a general suppression of progenitor cell populations including common lymphoid progenitors and common myeloid progenitors. Within the LSK population, DIO induced a shift in stem cells that are capable of self-renewal toward maturing multipotent progenitor cells. The higher differentiation potential resulted in increased lymphoid and myeloid ex vivo colony-forming capacity. In a competitive BM transplantation, BM from obese animals showed impaired multilineage reconstitution when transplanted into chow fed mice. Our data demonstrate that obesity stimulates the differentiation and reduces proliferation of HSPCs in the BM, leading to a decreased HSPC population. This implies that the effects of obesity on HSPCs hampers proper functioning of the immune system.-Van den Berg, S. M., Seijkens, T. T. P., Kusters, P. J. H., Beckers, L., den Toom, M., Smeets, E., Levels, J., de Winther, M. P. J., Lutgens, E. Diet-induced obesity in mice diminishes hematopoietic stem and progenitor cells in the bone marrow. PMID- 26813975 TI - The VP3 structural protein of foot-and-mouth disease virus inhibits the IFN-beta signaling pathway. AB - Foot-and-mouth disease is a frequently occurring disease of cloven-hoofed animals that is caused by infection with the foot-and-mouth virus (FMDV). FMDV circumvents the type-I IFN response by expressing proteins that antagonize cellular innate immunity, such as leader protease and 3C protease. We identified the FMDV structural protein VP3 as a negative regulator of the virus-triggered IFN-beta signaling pathway. Expression of FMDV VP3 inhibited the Sendai virus triggered activation of IFN regulatory factor-3 and the expression of retinoic acid-inducible gene-I/melanoma differentiation-associated protein-5. Transient transfection and coimmunoprecipitation confirmed that the structural protein VP3 interacts with virus-induced signaling adapter (VISA), which is dependent on the C-terminal aa 111-220 of VP3. In addition, we found that FMDV VP3 inhibits the expression of VISA by disrupting its mRNA. Taken together, our findings reveal a novel strategy used by the structural VP3 protein of FMDV to evade host innate immunity.-Li, D., Yang, W., Yang, F., Liu, H., Zhu, Z., Lian, K., Lei, C., Li, S., Liu, X., Zheng, H., Shu, H. The VP3 structural protein of foot-and-mouth disease virus inhibits the IFN-beta signaling pathway. PMID- 26813976 TI - Gradient COUP-TFI Expression Is Required for Functional Organization of the Hippocampal Septo-Temporal Longitudinal Axis. AB - The hippocampus (HP), a medial cortical structure, is subdivided into a distinct dorsal (septal) and ventral (temporal) portion, which is separated by an intermediate region lying on a longitudinal curvature. While the dorsal portion is more dedicated to spatial navigation and memory, the most ventral part processes emotional information. Genetic factors expressed in gradient during development seem to control the size and correct positioning of the HP along its longitudinal axis; however, their roles in regulating differential growth and in supporting its anatomical and functional dissociation remain unexplored. Here, we challenge the in vivo function of the nuclear receptor COUP-TFI (chicken ovalbumin upstream promoter transcription factor 1) in controlling the hippocampal, anatomical, and functional properties along its longitudinal axis. Loss of cortical COUP-TFI function results in a dysmorphic HP with altered shape, volume, and connectivity, particularly in its dorsal and intermediate regions. Notably, topographic inputs from the entorhinal cortex are strongly impaired in the dorsal portion of COUP-TFI mutants. These severe morphological changes are associated with selective spatial learning and memory impairment. These findings identify a novel transcriptional regulator required in the functional organization along the hippocampal septo-temporal axis supporting a genetic basis of the hippocampal volumetric growth with its final shape, circuit, and type of memory function. PMID- 26813978 TI - Indian diabetes lifestyle interventions work at many ages and weights. PMID- 26813977 TI - A new class of temporarily phenotypic enhancers identified by CRISPR/Cas9 mediated genetic screening. AB - With <2% of the human genome coding for proteins, a major challenge is to interpret the function of the noncoding DNA. Millions of regulatory sequences have been predicted in the human genome through analysis of DNA methylation, chromatin modification, hypersensitivity to nucleases, and transcription factor binding, but few have been shown to regulate transcription in their native contexts. We have developed a high-throughput CRISPR/Cas9-based genome-editing strategy and used it to interrogate 174 candidate regulatory sequences within the 1-Mbp POU5F1 locus in human embryonic stem cells (hESCs). We identified two classical regulatory elements, including a promoter and a proximal enhancer, that are essential for POU5F1 transcription in hESCs. Unexpectedly, we also discovered a new class of enhancers that contribute to POU5F1 transcription in an unusual way: Disruption of such sequences led to a temporary loss of POU5F1 transcription that is fully restored after a few rounds of cell division. These results demonstrate the utility of high-throughput screening for functional characterization of noncoding DNA and reveal a previously unrecognized layer of gene regulation in human cells. PMID- 26813979 TI - Rapid Response to the Call for More METs. PMID- 26813980 TI - Pediatric Medical Emergency Team Events and Outcomes: A Report of 3647 Events From the American Heart Association's Get With the Guidelines-Resuscitation Registry. AB - OBJECTIVES: To describe the clinical characteristics and outcomes of a large, multicenter cohort of pediatric medical emergency team (MET) events occurring in US hospitals reported to the American Heart Association's Get With the Guidelines Resuscitation registry. METHODS: We analyzed consecutive pediatric (<18 years) MET events reported to the registry from January 2006 to February 2012. RESULTS: We identified 3647 MET events from 151 US hospitals: 3080 (84%) ward and 567 (16%) telemetry/step-down unit events; median age 3.0 years (interquartile range: 0.0-11.0); 54% male; median duration 29 minutes (interquartile range: 18-49). Triggers included decreased oxygen saturation (32%), difficulty breathing (26%), and staff concern (24%). Thirty-seven percent (1137/3059) were admitted within 24 hours before MET event. Within 24 hours before the MET event, 16% were transferred from a PICU, 24% from an emergency department, and 7% from a pediatric anesthesia care unit. Fifty-three percent of MET events resulted in transfer to a PICU; 3251 (89%) received nonpharmacologic interventions, 2135 (59%) received pharmacologic interventions, 223 (6.1%) progressed to an acute respiratory compromise event, and 17 events (0.5%) escalated to cardiopulmonary arrest during the event. Survival to hospital discharge was 93.3% (n=3299/3536). CONCLUSIONS: Few pediatric MET events progress to respiratory or cardiac arrest, but most require nonpharmacologic and pharmacologic intervention. Median duration of MET event was 29 minutes (interquartile range: 18-49), and 53% required transfer to a PICU. Events often occurred within 24 hours after hospital admission or transfer from the PICU, emergency department, or pediatric anesthesia care unit and may represent an opportunity to improve triage and other systems of care. PMID- 26813981 TI - Clinical features and patency rates of Remedy(r) biodegradable peripheral stents. AB - OBJECTIVE: The aim of this study was to investigate the midterm results of Remedy(r) biodegradable stents, which have recently come into use for lower extremity arterial occlusive disease. METHODS: Sixty-five patients, who underwent surgical intervention in various cardiovascular surgery clinics throughout Turkey, were included in the study. The total number of stents used was 92. The mean age of the patients was 64.11 +/- 24.13 years (20-82), and 16 (24.6%) were female. The mean number of stents per patient was 1.42, and 70.7% of the lesions were TASC type A. Patients were followed for a mean of 32 months. Sixty-five patients underwent a control examination using either digital subtraction angiography or colour Doppler ultrasonography. In-stent restenosis was defined as >= 50% stenosis in the stent area in asymptomatic patients. The procedure was repeated if the degree of stenosis was >= 70%. RESULTS: During the follow-up period, restenosis (>=50% stenosis) was observed in seven patients (10.7%). The patency rate after secondary intervention was 100%, and there was no loss of limbs in any patient. Restenosis was observed in six patients with superficial femoral artery stents, and in one patient with a popliteal arterial stent. CONCLUSION: Our experience shows that Remedy(r) biodegradable peripheral stents were safe and effective in our cohort of patients, with acceptable patency rates. PMID- 26813982 TI - Varicocele and its effect on testosterone: implications for the adolescent. AB - The treatment of varicoceles in adolescents is highly controversial. In contrast to adults with varicocele, fertility status is not yet known and it is not generally feasible to obtain a semen analysis in adolescents in order to guide treatment. Hence, the principal indication for surgery in teenagers is hypotrophy/atrophy of the left testis associated with a varicocele. Recent evidence in adults suggests that varicocele may be a cause of hypogonadism. If this is further documented in adults, it may be true in teens as well and indeed, might be an indication for early surgery. This is an important area for research in adolescents with a varicocele. PMID- 26813983 TI - Proteome-wide analysis reveals widespread lysine acetylation of major protein complexes in the malaria parasite. AB - Lysine acetylation is a ubiquitous post-translational modification in many organisms including the malaria parasite Plasmodium falciparum, yet the full extent of acetylation across the parasite proteome remains unresolved. Moreover, the functional significance of acetylation or how specific acetyl-lysine sites are regulated is largely unknown. Here we report a seven-fold expansion of the known parasite 'acetylome', characterizing 2,876 acetylation sites on 1,146 proteins. We observe that lysine acetylation targets a diverse range of protein complexes and is particularly enriched within the Apicomplexan AP2 (ApiAP2) DNA binding protein family. Using quantitative proteomics we determined that artificial perturbation of the acetate/acetyl-CoA balance alters the acetyl lysine occupancy of several ApiAP2 DNA-binding proteins and related transcriptional proteins. This metabolic signaling could mediate significant downstream transcriptional responses, as we show that acetylation of an ApiAP2 DNA-binding domain ablates its DNA-binding propensity. Lastly, we investigated the acetyl-lysine targets of each class of lysine deacetylase in order to begin to explore how each class of enzyme contributes to regulating the P. falciparum acetylome. PMID- 26813984 TI - Rapid, sensitive separation of the three main isoflavones in soybean using immunoaffinity chromatography. AB - Daidzin, genistin, and glycitein are major isoflavone compounds in soybean that are indispensable nutrients in traditional Chinese foods. Generally, strategies for detecting and separating soy isoflavones have been based on HPLC and chromatographic techniques, which are tedious and time-consuming procedures. In the present study, we developed an ELISA-based approach for daidzin detection using a broad-specificity monoclonal antibody (clone number: AA9) with an effective detection range of 10-10 000 ng/mL. Subsequently, we prepared an immunoaffinity column by coupling the monoclonal antibody AA9 to CNBr-activated Sepharose 4B. Our results demonstrate that the immunoaffinity column can efficiently and specifically extract daidzin, glycitein, and genistin from numerous structurally similar soy isoflavones in leguminous plants, thereby providing a new method for the extraction of target components from similar compounds in natural products. PMID- 26813985 TI - Quetiapine safety in older adults: a systematic literature review. AB - WHAT IS KNOWN AND OBJECTIVE: Quetiapine is a second-generation antipsychotic that is commonly prescribed for a range of approved and off-label indications in older adults. However, little is known about its safety in this population. The available evidence on quetiapine safety is based on studies on second-generation antipsychotics as a group, often in the general population and for approved indications. There are no systematic reviews on the safety of quetiapine in older adults, and therefore, there is a need for systematically assessing quetiapine safety in this group of patients to establish an appropriate safety profile for this vulnerable population. The aim of this paper was to review and describe adverse drug events associated with quetiapine use in older adults. METHODS: A systematic literature search was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases searched were CINAHL, PubMed, Medline, PsycInfo and the Cochrane Library. RESULTS AND DISCUSSION: Sixty-nine papers met the inclusion criteria. The majority of the studies (n = 36, 52%) were observational, and 11 (16%) were randomized controlled trials (RCTs). Most of the reported indications (75%) were off-label. The most commonly reported adverse events were somnolence (25-39%), dizziness (15-27%), headache (10-23%), postural hypotension (6-18%) and weight gain (11-30%). From the included RCTs, comparing quetiapine with placebo, quetiapine resulted in significantly greater cognitive impairment, higher rates of falls and injury and increased mortality in patients with parkinsonism, but not in patients with dementia. Compared with risperidone and olanzapine, quetiapine had significantly lower risk of mortality, reduced rate of cerebrovascular events, increased rate of falls and injury and less metabolic disorders compared with olanzapine, but higher metabolic disorders compared with risperidone. WHAT IS NEW AND CONCLUSION: This work provides full characterization of quetiapine safety in older people, which may help healthcare providers better anticipate, prevent and manage ADEs in this population. PMID- 26813986 TI - Possible serotonin syndrome with carbidopa-levodopa and linezolid. AB - WHAT IS KNOWN AND OBJECTIVE: Serotonin syndrome (SS) can occur when linezolid is combined with other serotonergic agents. CASE DESCRIPTION: We report a case of possible SS in an elderly patient receiving linezolid in combination with carbidopa-levodopa (CL). WHAT IS NEW AND CONCLUSION: Although certain classes of agents are commonly reported as causing SS among patients receiving linezolid, there are no specific case reports detailing this reaction with CL. Linezolid combined with CL should generally be avoided; however, if linezolid must be used, discontinuation of other agents with serotonergic activity is recommended with careful monitoring for signs and symptoms of SS. PMID- 26813987 TI - Adverse event potentially due to an interaction between ibrutinib and verapamil: a case report. AB - WHAT IS KNOWN AND OBJECTIVE: Ibrutinib is a recently approved oral anticancer agent with pharmacokinetics that is very sensitive to metabolic inhibition. We report a serious side effect of ibrutinib potentially attributable to interaction with the moderate CYP3A4 inhibitor verapamil. CASE DESCRIPTION: A patient with mantle cell lymphoma was admitted to our emergency department with severe diarrhoea. During a prescription review, the clinical pharmacist identified a potential drug interaction between ibrutinib and verapamil present in a branded combination product also containing trandolapril. Ibrutinib was discontinued for 5 days, and verapamil was stopped. Lercanidipine 10 mg daily was prescribed as an alternative antihypertensive drug. The patient was discharged after 3 days with symptomatic treatment for his diarrhoea. Three months later, the patient maintained control with ibrutinib and olmesartan, but without verapamil. WHAT IS NEW AND CONCLUSION: This is the first description of a serious side effect of ibrutinib likely due to an interaction with the CYP3A4 inhibitor verapamil. Prescriptions of ibrutinib must be carefully checked to identify possible interactions with CYP3A4 inhibitors and patients monitored accordingly. PMID- 26813988 TI - Accuracy of PET/MR image coregistration of cervical lesions. AB - PURPOSE: This study aimed to evaluate the accuracy of sequential whole-body PET/MR image coregistration of cervical lesions. MATERIALS AND METHODS: Twenty five patients with cervical carcinomas underwent fluorine-18 fluorodeoxyglucose PET/MR before radiotherapy. MR-volumes of interest (VOIs), PET-VOIs, and apparent diffusion coefficient (ADC)-VOIs were outlined manually on T2-weighted MR images, PET images, and ADC maps. The difference between the lesion centers on PET and MR was determined by calculating the distance of the respective geometric center of gravity. In addition, the tumor volume contour differences were assessed using the dice similarity coefficient for PET and ADC. Results were analyzed by mean+/ SD and a two-sample t-test. RESULTS: The mean values of the center of gravity mismatch were relatively higher with lesions between PET and ADC (5.79+/-1.70 mm) than that between PET and MR-T2 (5.22+/-1.97 mm; P=0.304). Tumor location overlap difference between MR-T2 and PET images (0.64+/-0.13) was larger than that between ADC and PET (0.56+/-0.14; P=0.054). The average differences between the centers of lesions on PET and T2-weighted images were 6.25+/-1.91, 5.24+/-2.17, and 4.30+/-1.30 mm for MR-VOI less than 14, 14-62, and at least 62 ml. The average differences between the center of lesions on PET and ADC were 5.97+/ 1.48, 5.43+/-1.40, and 5.78+/-2.75 mm, respectively. Image registration tended to be slightly less accurate in the smaller lesions than in the larger lesions (P>0.05). The average overlaps were 0.51+/-0.13, 0.63+/-0.10, and 0.76+/-0.03 between the T2-weighted image and PET, respectively. The average overlaps were 0.44+/-0.14, 0.58+/-0.11, and 0.66+/-0.04 between the ADC and PET, respectively. Larger tumors had a higher degree of overlap compared with small tumors (P<0.05). CONCLUSION: Image coregistration of cervical lesions is usually accurate in sequential whole-body PET/MR. The accuracy of image registration between MR-T2 and PET was larger than that between ADC and PET. Image registration tended to be more accurate in the larger lesions. PMID- 26813989 TI - Individualized 131I-mIBG therapy in the management of refractory and relapsed neuroblastoma. AB - OBJECTIVE: Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) therapy is an established treatment modality for relapsed/refractory neuroblastoma, most frequently administered according to fixed or weight-based criteria. We evaluate response and toxicity following a dosimetry-based, individualized approach. MATERIALS AND METHODS: A review of 44 treatments in 25 patients treated with I mIBG therapy was performed. Patients received I-mIBG therapy following relapse (n=9), in refractory disease (n=12), or with surgically unresectable disease despite conventional treatment (n=4). Treatment schedule (including mIBG dose and number of administrations) was individualized according to the clinical status of the patient and dosimetry data from either a tracer study or previous administrations. Three-dimensional tumour dosimetry was also performed for eight patients. RESULTS: The mean administered activity was 11089+/-7222 MBq and the mean whole-body dose for a single administration was 1.79+/-0.57 Gy. Tumour absorbed doses varied considerably (3.70+/-3.37 mGy/MBq). CTCAE grade 3/4 neutropenia was documented following 82% treatments and grade 3/4 thrombocytopenia following 71% treatments. Further acute toxicity was found in 49% of patients. All acute toxicities resolved with appropriate therapy. The overall response rate was 58% (complete or partial response), with a further 29% of patients having stable disease. CONCLUSION: A highly personalized approach combining patient-specific dosimetry and clinical judgement enables delivery of high activities that can be tolerated by patients, particularly with stem cell support. We report excellent response rates and acceptable toxicity following individualized I-mIBG therapy. PMID- 26813990 TI - Clinical relevance of 18F-FDG-negative osteoblastic metastatic bone lesions noted on PET/CT in breast cancer patients. AB - PURPOSE: Our study aims to assess the clinical relevance of fluorine-18 fluorodeoxyglucose (F-FDG) negative osteoblastic metastatic bone lesions noted on PET/computed tomography (CT) in breast cancer patients. PATIENTS AND METHODS: The medical records of breast cancer patients were reviewed retrospectively from January 2012 until April 2015. We included the patients who had metastatic bone disease evaluated by F-FDG-PET/CT. Group 1 included patients with newly diagnosed metastatic bone disease at the time of imaging and group 2 included patients with a history of treated metastatic bone disease at the time of imaging. Functional and structural bone abnormality was monitored on F-FDG-PET/CT scans. RESULTS: Fifty-three patients, median age 47.1 years (range 27-80 years), were included. Group 1 included 35 patients. Of those, 88% had predominantly F-FDG-avid osteolytic and mixed lesions (destructive pattern). Complete response was noted in 65% of the patients after treatment, evidenced by disappearance of bony focal activity with partial or total ossification of most osteolytic lesions converting into mixed and 'secondary' osteoblastic lesions. In addition, more ossified lesions were noted in some patients whose lesions were left untreated for long time (aged lesions). The remaining 12% of group 1 patients had pure 'primary' osteoblastic lesions (nondestructive pattern), which started small and expanded with time and tend to be F-FDG-negative. Group 2 included 18 patients who had predominantly mixed and 'secondary' osteoblastic lesions. CONCLUSION: We described two types of osteoblastic metastatic bone lesions in breast cancer patients: 'primary' and 'secondary'. 'Secondary' lesions (88%) are totally ossified (healed) osteolytic lesions and are almost always F-FDG-negative on PET/CT. These lesions are of no clinical importance. Healing is potentially seen after treatment or if the lesions are left untreated for a long time (aged lesions). 'Primary' lesions (12%) are seen without previous bone destruction and tend to be F-FDG-negative, although they contain tumor cells. Hence, sequential CT is more helpful than sequential FDG-PET in following 'primary' lesions. PMID- 26813991 TI - The role of 18F-FDG PET/CT in the follow-up of well-differentiated thyroid cancer with negative thyroglobulin but positive and/or elevated antithyroglobulin antibody. AB - Thyroglobulin measurement is the most sensitive and important indicator of persistent and/or recurrent disease in the follow-up of well-differentiated thyroid cancer (DTC) after total thyroidectomy and radioiodine ablation therapy. However, positive or elevated thyroglobulin autoantibody (TgAb) interferes with the accurate measurement of serum thyroglobulin and may mask the presence of a recurrent and/or metastatic disease. It was reported that persistently positive TgAb could be viewed as evidence of the continued presence of functional thyroid cells, either benign or malignant, and elevated TgAb might indicate the recurrent and/or metastatic disease and could be used as an alternative of the tumor marker for DTC. However, the clinical application and usefulness of TgAb for the follow up of DTC are uncertain. Imaging studies such as the neck ultrasound and whole body radioiodine are still used widely for the detection of the lesions. Although it is not used routinely in DTC, limited clinical observations showed that fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography could be an additive valuable imaging modality in the detection of recurrent and/or metastatic disease in these patients, with promising sensitivity and specificity. A negative F-FDG PET/computed tomography result was associated with the absence of active disease and disappearing TgAb over time, and F-FDG-avid residual/recurrent/metastatic lesions were associated with aggressive disease, poor outcome, and persistently increased TgAb levels. PMID- 26813992 TI - Comparison of 18F-FDG PET/CT scan and 99mTc-MDP bone scintigraphy in detecting bone metastasis in head and neck tumors. AB - PURPOSE: The aim of this study was to evaluate the efficacy of fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) compared with bone scan in detecting bone metastases in patients with head and neck cancer. MATERIALS AND METHODS: A total of 319 patients with head and neck cancer were identified in our database who had undergone F-FDG PET/CT, from January 2006 until June 2007. Of them 156 patients (age range 15-100 years) met our inclusion criteria - namely, biopsy-proven head and neck cancer, and bone scan and F-FDG PET/CT within 30 days. Comparison was made on a lesion-by-lesion analysis. MRI, multidetector CT, and the clinical course of the patients were our references. RESULTS: F-FDG PET/CT identified (n=213) bone lesions in 18 patients, in addition to distant metastases in solid organs such as the liver and lung, lymphadenopathy above and below the diaphragm, and adrenal glands in 12 patients. However, bone scan identified (n=198) 16 patients. Bone scan missed two patients with confirmed bone metastases by means of biopsy in one patient and radiologically in the second. F FDG PET/CT showed true-positive results in 18 patients, whereas bone scan showed true-positive results in 16 patients. F-FDG PET/CT showed true-negative results in 138 patients, whereas bone scan showed true-negative results in 134 patients. F-FDG PET/CT showed no false-positive or false-negative results. However, bone scan had two false-positive and two false-negative results. The overall sensitivity, specificity, and accuracy was 100% for F-FDG PET/CT and 88, 98, and 96%, respectively, for bone scan. CONCLUSION: F-FDG PET/CT is superior to Tc methylene diphosphonate bone scan in detecting bone metastases in head and neck cancer. PMID- 26813994 TI - Factors related to falls, weight-loss and pressure ulcers--more insight in risk assessment among nursing home residents. AB - AIMS AND OBJECTIVES: To describe how the included items in three different scales, Downton Fall Risk Index, the short form of Mini Nutritional Assessment and the Modified Norton Scale are associated to severe outcomes as falls, weight loss and pressure ulcers. BACKGROUND: Falls, malnutrition and pressure ulcers are common adverse events among nursing home residents and risk scoring are common preventive activities, mainly focusing on single risks. In Sweden the three scales are routinely used together with the purpose to improve the quality of prevention. DESIGN: Longitudinal quantitative study. METHODS: Descriptive analyses and Cox regression analyses. RESULTS: Only 4% scored no risk for any of these serious events. Longitudinal risk scoring showed significant impaired mean scores indicating increased risks. This confirms the complexity of this population's status of general condition. There were no statistical significant differences between residents categorised at risk or not regarding events. Physical activity increased falls, but decreased pressure ulcers. For weight loss, cognitive decline and the status of general health were most important. CONCLUSIONS: Risk tendencies for falls, malnutrition and pressure ulcers are high in nursing homes, and when measure them at the same time the majority will have several of these risks. Items assessing mobility or items affecting mobility were of most importance. Care processes can always be improved and this study can add to the topic. RELEVANCE TO CLINICAL PRACTICE: A more comprehensive view is needed and prevention can not only be based on total scores. Mobility is an important factor for falls and pressure ulcers, both as a risk factor and a protective factor. This involves a challenge for care--to keep the inmates physical active and at the same time prevent falls. PMID- 26813995 TI - Obligatory parthenogenesis and TE load: Bacillus stick insects and the R2 non-LTR retrotransposon. AB - Transposable elements (TEs) are selfish genetic elements whose self-replication is contrasted by the host genome. In this context, host reproductive strategies are predicted to impact on both TEs load and activity. The presence and insertion distribution of the non-LTR retrotransposon R2 was here studied in populations of the strictly bisexual Bacillus grandii maretimi and of the obligatory parthenogenetic Bacillus atticus atticus. Furthermore, data were also obtained from the offspring of selected B. a. atticus females. At the population level, the gonochoric B. g. maretimi showed a significantly higher R2 load than the obligatory parthenogenetic B. a. atticus. The comparison with bisexual and unisexual Bacillus rossius populations showed that their values were higher than those recorded for B. a. atticus and similar, or even higher, than those of B. g. maretimi. Consistently, an R2 load reduction is scored in B. a. atticus offspring even if with a great variance. On the whole, data here produced indicate that in the obligatory unisexual B. a. atticus R2 is active and that mechanisms of molecular turnover are effective. Furthermore, progeny analyses show that, at variance of the facultative parthenogenetic B. rossius, the R2 activity is held at a lower rate. Modeling parental-offspring inheritance, suggests that in B. a. atticus recombination plays a major role in eliminating insertions rather than selection, as previously suggested for unisexual B. rossius progeny, even if in both cases a high variance is observed. In addition to this, mechanisms of R2 silencing or chances of clonal selection cannot be ruled out. PMID- 26813997 TI - Implementing Recommendations for Depression Screening of Adults: How Can Neurology Contribute to the Dialogue? PMID- 26813996 TI - TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL. AB - Translationally Controlled Tumor Protein (TCTP) is anti-apoptotic, key in development and cancer, however without the typical Bcl2 family members' structure. Here we report that TCTP contains a BH3-like domain and forms heterocomplexes with Bcl-xL. The crystal structure of a Bcl-xL deletion variant TCTP11-31 complex reveals that TCTP refolds in a helical conformation upon binding the BH3-groove of Bcl-xL, although lacking the h1-subregion interaction. Experiments using in vitro-vivo reconstituted systems and TCTP(+/-) mice indicate that TCTP activates the anti-apoptotic function of Bcl-xL, in contrast to all other BH3-proteins. Replacing the non-conserved h1 of TCTP by that of Bax drastically increases the affinity of this hybrid for Bcl-xL, modifying its biological properties. This work reveals a novel class of BH3-proteins potentiating the anti-apoptotic function of Bcl-xL. PMID- 26813998 TI - Are You a Change Agent? PMID- 26813999 TI - Securing the Literature Now and in the Future. PMID- 26814000 TI - Caring for the Patient With Limited Systemic Scleroderma. AB - Systemic scleroderma (systemic sclerosis) is a rare, autoimmune, collagen vascular disease of unknown etiology that affects the connective tissues of the skin, internal organs, as well as the small blood vessels. There are 3 subclasses of systemic scleroderma: limited cutaneous, diffuse cutaneous, and sine scleroderma. Prognosis depends on the extent of organ involvement. Complications of systemic scleroderma can involve the cardiovascular, pulmonary, gastrointestinal, renal, integumentary, and the skeletal-muscular systems. Because systemic scleroderma is not common, many orthopaedic nurses may be unfamiliar with how to best provide care. This article provides information about the complexity of the different types of this disease and the basic nursing care of the patient with the most common subclass of systemic scleroderma, limited cutaneous systemic scleroderma. PMID- 26814002 TI - Comparison of Two Postoperative Bowel Regimens in Children With Scoliosis Repair. AB - BACKGROUND: Orthopaedic procedures place children at risk for postoperative constipation due to combined effects of anesthesia, narcotics, and decreased physical mobility. PURPOSE: This retrospective study analyzed medication use and stool outcomes of 36 children who received polyethylene glycol 3350 (PEG) or mineral oil (MO) after a spinal fusion. METHODS AND RESULTS: A chart review found no statistical differences by group for number of bowel movements (BMs) before discharge (p = .37), time from procedure to BM, use of rescue cathartics (p = .55), or medication refusal (p = .37). In the PEG group, 90% refused the medication one or more times compared with 75% in the MO group. CONCLUSION: Only 17% of patients had a BM before discharge. Findings suggest medication refusal may be related to the method of medication preparation, suggesting the child's choice in bowel regimens may be indicated. A prospective study with a larger, randomized sample size is needed. PMID- 26814004 TI - A Randomized Controlled Trial of an Individualized Preoperative Education Intervention for Symptom Management After Total Knee Arthroplasty. AB - Pain and nausea limit recovery after total knee arthroplasty (TKA) patients. The aim of this study was to determine the effect of a preoperative educational intervention on postsurgical pain-related interference in activities, pain, and nausea. Participants (n = 143) were randomized to intervention or standard care. The standard care group received the usual teaching. The intervention group received the usual teaching, a booklet containing symptom management after TKA, an individual teaching session, and a follow-up support call. Outcome measures assessed pain, pain interference, and nausea. There were no differences between groups in patient outcomes. There were no group differences for pain at any time point. Respondents had severe postoperative pain and nausea and received inadequate doses of analgesia and antiemetics. Individualizing education content was insufficient to produce a change in symptoms for patients. Further research involving the modification of system factors affecting the provision of symptom management interventions is warranted. PMID- 26814005 TI - Educational Intervention Impact on Osteoporosis Knowledge, Health Beliefs, Self Efficacy, Dietary Calcium, and Vitamin D Intakes in Young Adults. AB - BACKGROUND: Successful prevention of osteoporosis begins early in life. Adequate intake of calcium and vitamin D plays a role in this prevention along with knowledge, health beliefs, and self-efficacy related to preventive dietary behaviors. PURPOSE: The purpose of this theory-based study was to examine young adults' knowledge of osteoporosis, health beliefs, self-efficacy, dietary calcium, and vitamin D intakes as measures of preventive behaviors. METHODS: A pre-/posttest design was used to determine knowledge, health beliefs, and self efficacy. A convenience sample of young adults (n = 153) was obtained at a Midwestern college. Participants completed pre- and postquestionnaires that included an osteoporosis knowledge test, health belief scale, self-efficacy scale, and 3-day food records. RESULTS: Health beliefs were a significant predictor of dietary calcium intake and vitamin D intake. Both interventions increased osteoporosis knowledge and health beliefs but not self-efficacy. No differences were found between genders. Both interventions did not significantly alter dietary behavior; however, average dietary calcium intake met current recommendations. CONCLUSION: Either educational method could be implemented in courses or community education to increase knowledge and health beliefs. PMID- 26814007 TI - Catching Up on New Medications: New FDA Approvals. AB - Despite all efforts of the Federal Drug Administration to release timely and accurate information about new drug approvals, marketing and media announcements about new drugs may be incomplete, misinterpreted, or misunderstood. Informed and knowledgeable nurses are able to educate patients about new medications: they can clarify misunderstandings or misconceptions and significantly reduce the potential for harm. In this article, selected examples of new brand name drugs and first-time generics approved this year are discussed. PMID- 26814009 TI - Anterior Process Fracture of the Calcaneus: A Case Report and Discussion. PMID- 26814013 TI - Triticale allergy in a farmer. AB - We present the case of a 29-year-old farmer with hay fever and atopic dermatitis since adolescence who had developed work-related asthma about 5 years earlier. He was sensitized to grass pollen, wheat and rye flour, dust from the floors of the animal facilities (cows and pigs) and grain barn, and a battery of animal feed from his farm. Work-relatedness of his asthma was demonstrated by serial measurements of spirometry and fractional exhaled nitric oxide at work and during a holiday. Immunoblot analyses revealed dominant IgE-binding to grass pollen and triticale (a hybrid of rye and wheat). IgE inhibition experiments demonstrated that sensitization to triticale was not due to cross-reactivity to grass pollen. Testing of specific IgE-antibodies to recombinant wheat allergens showed sensitizations to profilin, peroxidase, and nonspecific lipid transfer proteins type I subfamily 9.1 and 9.7. We conclude that triticale allergy may occur as a distinct allergy in farmers. Am. J. Ind. Med. 59:501-505, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26814016 TI - Screening for Depression--A Tale of Two Questions. PMID- 26814017 TI - Emergent core values: the student perspective. AB - BACKGROUND: Certain moral and ethical values are expected of doctors, and these values are usually formed and consolidated at medical school. The efficacy of didactic teaching of values such as compassion and empathy has been disputed. Additionally, it is not clear if the values that students actually develop during undergraduate training are concordant with those outlined by national legislative and governing bodies. METHOD: A total of 24 final-year medical students participated in semi-structured interviews, which explored the values that they recognise in themselves and in their colleagues. The resultant data were thematically analysed to establish core themes. These themes represent the values that students hold in the highest regard. RESULTS: Analysis yielded three overarching themes: personal fortitude, which relates to the nurturing of the inner strength of the trainee; establishment of the ego, which pertains to the developing sense of self as a doctor; and striving for professional maturity, which refers to the cultivation of humane and compassionate care and interpersonal communication. The efficacy of didactic teaching of values such as compassion and empathy has been disputed FINDINGS: The moral values that are constructed in undergraduates centre around maintaining personal well-being, establishing an identity as a medical professional and delivering compassionate care as part of a team. Most values align with those described by professional bodies and educators, but a minority are new findings, and relate to student welfare. Although there are validated assessment tools that measure the trainees' emotional intelligence and adherence to universally approved values, this study delineates the core principles valued by the students themselves. Understanding these principles grants teachers the opportunity to facilitate personal and professional development, and to foster humane and caring values. PMID- 26814015 TI - Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity. AB - The hepatic tricarboxylic acid (TCA) cycle is central to integrating macronutrient metabolism and is closely coupled to cellular respiration, free radical generation, and inflammation. Oxidative flux through the TCA cycle is induced during hepatic insulin resistance, in mice and humans with simple steatosis, reflecting early compensatory remodeling of mitochondrial energetics. We hypothesized that progressive severity of hepatic insulin resistance and the onset of nonalcoholic steatohepatitis (NASH) would impair oxidative flux through the hepatic TCA cycle. Mice (C57/BL6) were fed a high-trans-fat high-fructose diet (TFD) for 8 wk to induce simple steatosis and NASH by 24 wk. In vivo fasting hepatic mitochondrial fluxes were determined by(13)C-nuclear magnetic resonance (NMR)-based isotopomer analysis. Hepatic metabolic intermediates were quantified using mass spectrometry-based targeted metabolomics. Hepatic triglyceride accumulation and insulin resistance preceded alterations in mitochondrial metabolism, since TCA cycle fluxes remained normal during simple steatosis. However, mice with NASH had a twofold induction (P< 0.05) of mitochondrial fluxes (MUmol/min) through the TCA cycle (2.6 +/- 0.5 vs. 5.4 +/- 0.6), anaplerosis (9.1 +/- 1.2 vs. 16.9 +/- 2.2), and pyruvate cycling (4.9 +/- 1.0 vs. 11.1 +/- 1.9) compared with their age-matched controls. Induction of the TCA cycle activity during NASH was concurrent with blunted ketogenesis and accumulation of hepatic diacylglycerols (DAGs), ceramides (Cer), and long-chain acylcarnitines, suggesting inefficient oxidation and disposal of excess free fatty acids (FFA). Sustained induction of mitochondrial TCA cycle failed to prevent accretion of "lipotoxic" metabolites in the liver and could hasten inflammation and the metabolic transition to NASH. PMID- 26814014 TI - Glucose uptake and lipid metabolism are impaired in epicardial adipose tissue from heart failure patients with or without diabetes. AB - Type 2 diabetes mellitus is a complex metabolic disease, and cardiovascular disease is a leading complication of diabetes. Epicardial adipose tissue surrounding the heart displays biochemical, thermogenic, and cardioprotective properties. However, the metabolic cross-talk between epicardial fat and the myocardium is largely unknown. This study sought to understand epicardial adipose tissue metabolism from heart failure patients with or without diabetes. We aimed to unravel possible differences in glucose and lipid metabolism between human epicardial and subcutaneous adipocytes and elucidate the potential underlying mechanisms involved in heart failure. Insulin-stimulated [(14)C]glucose uptake and isoproterenol-stimulated lipolysis were measured in isolated epicardial and subcutaneous adipocytes. The expression of genes involved in glucose and lipid metabolism was analyzed by reverse transcription-polymerase chain reaction in adipocytes. In addition, epicardial and subcutaneous fatty acid composition was analyzed by high-resolution proton nuclear magnetic resonance spectroscopy. The difference between basal and insulin conditions in glucose uptake was significantly decreased (P= 0.006) in epicardial compared with subcutaneous adipocytes. Moreover, a significant (P< 0.001) decrease in the isoproterenol stimulated lipolysis was also observed when the two fat depots were compared, and it was strongly correlated with lipolysis, lipid storage, and inflammation related gene expression. Moreover, the fatty acid composition of these tissues was significantly altered by diabetes. These results emphasize potential metabolic differences between both fat depots in the presence of heart failure and highlight epicardial fat as a possible therapeutic target in situ in the cardiac microenvironment. PMID- 26814018 TI - Redeeming Lost Mothers: Adolescent Antiretroviral Treatment and the Making of Home in South Africa. AB - In this article, we explore how adolescent antiretroviral treatment (ART) might be signified to repair sociality in Eastern Cape homes that have been ruptured by HIV/AIDS and maternal loss. The post-apartheid period has exposed these families to new forms of social fragmentation, propelled by the disintegration of wage labor, declining marriage rates, and a rampant HIV/AIDS epidemic. Drawing on eight months of ethnographic fieldwork (August 2013-April 2014), we show that in the homes of some adolescents born with HIV, these present-day domestic ruptures were discursively connected to the past shortcomings of their dead and absent mothers. In some familial narratives lost mothers were accused of disobeying their elders, neglecting their children, and flouting custom; their social transgressions were made manifest in their child's inherited HIV. By signifying adolescent ART-taking as an enactment of the discipline and care purportedly absent in their mothers, these families might also attempt to imbue ART, beyond its biomedical function, as a means of social repair. PMID- 26814019 TI - Age-space-time CAR models in Bayesian disease mapping. AB - Mortality counts are usually aggregated over age groups assuming similar effects of both time and region, yet the spatio-temporal evolution of cancer mortality rates may depend on changing age structures. In this paper, mortality rates are analyzed by region, time period and age group, and models including space-time, space-age, and age-time interactions are considered. The integrated nested Laplace approximation method, known as INLA, is adopted for model fitting and inference in order to reduce computing time in comparison with Markov chain Monte Carlo (McMC) methods. The methodology provides full posterior distributions of the quantities of interest while avoiding complex simulation techniques. The proposed models are used to analyze prostate cancer mortality data in 50 Spanish provinces over the period 1986-2010. The results reveal a decline in mortality since the late 1990s, particularly in the age group [65,70), probably because of the inclusion of the PSA (prostate-specific antigen) test and better treatment of early-stage disease. The decline is not clearly observed in the oldest age groups. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26814020 TI - Single-molecule Spectroscopy: Exploring Heterogeneity in Chemical and Biological Systems. AB - Many chemical and biological systems are heterogeneous in the molecular length scale (~ 1 nm). Heterogeneity in many chemical systems and organized assemblies may be monitored using single-molecule spectroscopy (SMS). In SMS, the size of the focal spot (i.e., the smallest region to be probed) is nearly half of the excitation wavelength (lambda/2, i.e., 200-375 nm) for visible light (400-750 nm). We discuss how one can get spatial resolutions better than 200 nm using molecules as nanometric probes. We show that polymer hydrogels, lipid vesicles, room temperature ionic liquids (RTILs), and binary liquid mixtures exhibit such heterogeneity. Another important observation is solute-dependent friction in RTILs. In an RTIL, diffusion of an ionic solute is slower than that of a neutral solute. PMID- 26814022 TI - Tetrel Bonding Interactions. AB - Tetrel (Tr) bonding is first placed into perspective as a sigma-hole bonding interaction with atoms of the Tr family. An sp(3) R4Tr unit has four sigma-holes with which a Lewis base can form a complex. We then highlight some inspiring crystal structures where Tr bonding is obvious, followed by an account of our own work. We have shown that Tr bonding is ubiquitous in the solid state and we have highlighted that Tr bonding with carbon is possible when C is placed in the appropriate chemical context. We hope that this account serves as an initial guide and source of inspiration for others wishing to exploit this vastly underexplored interaction. PMID- 26814021 TI - Serum NT-proCNP levels increased after initiation of GH treatment in patients with achondroplasia/hypochondroplasia. AB - OBJECTIVE: Serum amino-terminal propeptide of C-type natriuretic peptide (NT proCNP) levels have been proposed as a biomarker of linear growth in healthy children. The usefulness of NT-proCNP in patients with achondroplasia (ACH)/hypochondroplasia (HCH) remains to be elucidated. The objective was to study whether serum NT-proCNP level is a good biomarker for growth in ACH/HCH and other patients of short stature. DESIGN: This was a longitudinal cohort study. PATIENTS: Sixteen children with ACH (aged 0.4-4.3 years), six children with HCH (2.7-6.3 years), 23 children with idiopathic short stature (ISS) (2.2-9.0 years), eight short children with GH deficiency (GHD) (2.9-6.8 years) and five short children born small for gestational age (SGA) (2.0-6.6 years). Patients with ACH/HCH received GH treatment for 1 year. MEASUREMENTS: Serum NT-proCNP levels and height were measured. RESULTS: NT-proCNP levels positively correlated with height velocity in these short children (P < 0.05, r = 0.27). NT-proCNP levels inversely correlated with age in children with ISS alone (P < 0.01, r = -0.55). Serum NT-proCNP levels in patients with ACH/HCH were increased 3 months following the initiation of GH treatment (P < 0.05). Height SDS gain during GH treatment for 1 year was positively correlated with the changes in NT-proCNP levels after the initiation of GH (P < 0.01, r = 0.72). CONCLUSION: Serum NT-proCNP levels may be a good biomarker to indicate the effect of GH treatment on growth in patients with ACH/HCH at least in the first year and height velocity in short stature patients. PMID- 26814023 TI - Synthesis and biocompatibility of a biodegradable and functionalizable thermo sensitive hydrogel. AB - Injectable thermal gels are a useful tool for drug delivery and tissue engineering. However, most thermal gels do not solidify rapidly at body temperature (37 degrees C). We addressed this by synthesizing a thermo-sensitive, rapidly biodegrading hydrogel. Our hydrogel, poly(ethylene glycol)-co poly(propanol serinate hexamethylene urethane) (EPSHU), is an ABA block copolymer comprising A, methoxy poly ethylene glycol group and B, poly (propanol L-serinate hexamethylene urethane). EPSHU was characterized by gel permeation chromatography for molecular weight and (1)H NMR and Fourier transformed infrared for structure. Rheological studies measured the phase transition temperature. In vitro degradation in cholesterol esterase and in Dulbecco's phosphate buffered saline (DPBS) was tracked using the average molecular weight measured by gel permeation chromatography. LIVE/DEAD and resazurin reduction assays performed on NIH 3T3 fibroblasts exposed to EPSHU extracts demonstrated no cytotoxicity. Subcutaneous implantation into BALB/cJ mice indicated good biocompatibility in vivo. The biodegradability and biocompatibility of EPSHU together make it a promising candidate for drug delivery applications that demand carrier gel degradation within months. PMID- 26814024 TI - Handing over the reins. PMID- 26814025 TI - 'Like a Virgin': Hymenoplasty and Secret Marriage in Egypt. AB - In Egypt, women seek hymenoplasty to disguise evidence of premarital sexual intercourse. Physicians hide the fact that they perform the procedure, and laypeople condemn it as against religion and morality, a way of cheating men of knowledge of their wives' sexual history. Yet high-ranking religious leaders have condoned hymenoplasty. Based on ethnographic fieldwork, archival research, and formal interviews with laypeople and physicians, in this article, I investigate this discrepancy between religious and lay opinions. Many Egyptians believe women resort to hymenoplasty after contracting secret 'urfi (customary) marriages, and I examine the relationship between hymenoplasty and extramarital and paramarital sexuality. Egyptian debates around hymenoplasty and marriage are concerned with the notion that women's sexual status must be socially visible, believing that doctors and kin have the ability and obligation to read women's sexual history through physiological markers and social rituals. Hymenoplasty and secret marriage render women's sexual histories illegible to observers. PMID- 26814027 TI - Where are the Patients in Pediatric Patient Satisfaction Surveys? PMID- 26814026 TI - Towards do-it-yourself planar optical components using plasmon-assisted etching. AB - In recent years, the push to foster increased technological innovation and basic scientific and engineering interest from the broadest sectors of society has helped to accelerate the development of do-it-yourself (DIY) components, particularly those related to low-cost microcontroller boards. The attraction with DIY kits is the simplification of the intervening steps going from basic design to fabrication, albeit typically at the expense of quality. We present herein plasmon-assisted etching as an approach to extend the DIY theme to optics, specifically the table-top fabrication of planar optical components. By operating in the design space between metasurfaces and traditional flat optical components, we employ arrays of Au pillar-supported bowtie nanoantennas as a template structure. To demonstrate, we fabricate a Fresnel zone plate, diffraction grating and holographic mode converter--all using the same template. Applications to nanotweezers and fabricating heterogeneous nanoantennas are also shown. PMID- 26814029 TI - Information Curation among Vaccine Cautious Parents: Web 2.0, Pinterest Thinking, and Pediatric Vaccination Choice. AB - To learn about pediatric vaccine decision-making, we surveyed and interviewed US parents with at least one child kindergarten age or younger (N = 53). Through an anthropologically informed content analysis, we found that fully vaccinating parents (n = 33) mostly saw vaccination as routine. In contrast, selective and nonvaccinating parents (n = 20) exhibited the type of self-informed engagement that the health care system recommends. Selective vaccinators also expressed multiple, sometimes contradictory positions on vaccination that were keyed to individual children's biologies, child size, environmental hazards, specific diseases, and discrete vaccines. Rather than logical progressions, viewpoints were presented as assembled collections, reflecting contemporary information filtering and curation practices and the prevalence of collectively experienced and constructed digital "hive" narratives. Findings confirm the need for a noncategorical approach to intervention that accommodates the fluid, polyvalent nature of vaccine reasoning and the curatorial view selectively vaccinating parents take toward information while honoring their efforts at engaged healthcare consumption. PMID- 26814030 TI - Raman spectroscopy detects phenotypic differences among Escherichia coli enriched for 1-butanol tolerance using a metagenomic DNA library. AB - Advances in Raman spectroscopy are enabling more comprehensive measurement of microbial cell chemical composition. Advantages include results returned in near real-time and minimal sample preparation. In this research, Raman spectroscopy is used to analyze E. coli with engineered solvent tolerance, which is a multi-genic trait associated with complex and uncharacterized phenotypes that are of value to industrial microbiology. To generate solvent tolerant phenotypes, E. coli transformed with DNA libraries are serially enriched in the presence of 0.9% (v/v) and 1.1% (v/v) 1-butanol. DNA libraries are created using degenerate oligonucleotide primed PCR (DOP-PCR) from the genomic DNA of E. coli, Clostridium acetobutylicum ATCC 824, and the metagenome of a stream bank soil sample, which contained DNA from 72 different phyla. DOP-PCR enabled high efficiency library cloning (with no DNA shearing or end-polishing) and the inclusion un-culturable organisms. Nine strains with improved tolerance are analyzed by Raman spectroscopy and vastly different solvent-tolerant phenotypes are characterized. Common among these are improved membrane rigidity from increasing the fraction of unsaturated fatty acids at the expense of cyclopropane fatty acids. Raman spectroscopy offers the ability to monitor cell phenotype changes in near real time and is adaptable to high-throughput screening, making it relevant to metabolic engineering. PMID- 26814031 TI - Improving outpatient implementation of preexposure prophylaxis in men who have sex with men. AB - BACKGROUND AND PURPOSE: Preexposure prophylaxis (PrEP) has been shown to decrease the transmission of human immunodeficiency virus (HIV) when used in high-risk populations including men who have sex with men. However, despite effectiveness, there is underutilization in the outpatient setting. This review aims to assess the facilitators and barriers to improve outpatient utilization. METHODS: A systematic search of four databases, CINAHL, Ovid, Scopus, and PsychINFO, during March-May of 2015. A total of 22 articles were included for review. CONCLUSIONS: Barriers to utilization were either patient or provider centered. Patient barriers included a significant lack of knowledge, stigma, risk-taking, and adherence. Provider barriers also included lack of knowledge of treatment and protocols as well as fears of resistance and behavior change. Facilitators included adherence regimens, education, and comprehensive care. IMPLICATIONS FOR PRACTICE: Men who have sex with men are a high-risk population for HIV transmission. PrEP is successful in this subgroup at reducing transmission. Through education, nonjudgmental and comprehensive care providers can utilize PrEP to decrease transmission. PMID- 26814034 TI - Colloid fluids in adult anesthesia and ICU. PMID- 26814035 TI - Making a case for use of the pretracheal stethoscope in pediatric procedural sedation. PMID- 26814032 TI - Global metagenomic survey reveals a new bacterial candidate phylum in geothermal springs. AB - Analysis of the increasing wealth of metagenomic data collected from diverse environments can lead to the discovery of novel branches on the tree of life. Here we analyse 5.2 Tb of metagenomic data collected globally to discover a novel bacterial phylum ('Candidatus Kryptonia') found exclusively in high-temperature pH-neutral geothermal springs. This lineage had remained hidden as a taxonomic 'blind spot' because of mismatches in the primers commonly used for ribosomal gene surveys. Genome reconstruction from metagenomic data combined with single cell genomics results in several high-quality genomes representing four genera from the new phylum. Metabolic reconstruction indicates a heterotrophic lifestyle with conspicuous nutritional deficiencies, suggesting the need for metabolic complementarity with other microbes. Co-occurrence patterns identifies a number of putative partners, including an uncultured Armatimonadetes lineage. The discovery of Kryptonia within previously studied geothermal springs underscores the importance of globally sampled metagenomic data in detection of microbial novelty, and highlights the extraordinary diversity of microbial life still awaiting discovery. PMID- 26814036 TI - The pretracheal stethoscope useful, but not a necessity. PMID- 26814037 TI - Intranasal dexmedetomidine: an effective sedative agent for electroencephalogram and auditory brain response testing. AB - OBJECTIVE: Dexmedetomidine is an alpha2 agonist with sedative, anxiolytic, and analgesic properties. The intranasal (IN) route avoids the pain of intravenous (i.v.) catheter placement but limited literature exists on the use of IN dexmedetomidine. This study examines the effectiveness and safety of IN dexmedetomidine for sedation of patients undergoing electroencephalogram (EEG) and auditory brain response (ABR) testing. STUDY DESIGN: This was a review of all outpatients sedated with IN dexmedetomidine for EEG or ABR between October 1, 2012 and October 1, 2014. An initial dose of 2.5-3 MUg . kg(-1) IN dexmedetomidine was given with a repeat dose of 1-1.5 MUg . kg(-1) IN if needed 30 min later. Prospectively entered patient information was extracted from a quality assurance database and additional information gathered via retrospective chart review. RESULTS: Intranasal dexmedetomidine was used in 169 patients (EEG = 117, ABR = 52). First-dose success rates were 90.4% for ABR and 87.2% for EEG. Total success rates (with one or two doses of IN dexmedetomidine) were 100% for ABR and 99.1% for EEG. The median time to onset of sleep was 25 min (IQR, 20-32 min). The median duration of sedation was 107 min (IQR, 90-131 min). Adverse events included: 18 patients (10.7%) with hypotension which resolved without intervention, six patients with oxygen desaturation <90%, two of whom received supplemental oxygen, and one patient with an underlying upper airway abnormality who was treated with continuous positive airway pressure. CONCLUSIONS: IN dexmedetomidine is an effective and noninvasive method of sedating children for EEG and ABR. PMID- 26814038 TI - A prospective, randomized, double-blind trial of intranasal dexmedetomidine and oral chloral hydrate for sedated auditory brainstem response (ABR) testing. AB - BACKGROUND: Dexmedetomidine is increasingly used by various routes for pediatric sedation. However, there are few randomized controlled trials comparing the efficacy of dexmedetomidine to other commonly used sedatives. AIM: To compare the efficacy of sedation with intranasal dexmedetomidine to oral chloral hydrate for auditory brainstem response (ABR) testing. METHODS: In this double-blind, double dummy study, children undergoing ABR testing were randomized to receive intranasal dexmedetomidine 3 mcg . kg(-1) plus oral placebo (Group IN DEX) or oral chloral hydrate 50 mg . kg(-1) plus intranasal saline placebo (Group CH). We recorded demographic data, times from sedative administration to start and completion of testing, quality of sedation, occurrence of predefined adverse events, discharge times, and return to baseline activity on the day of testing. RESULTS: Testing completion rates with a single dose of medication were higher in the IN DEX group (89% vs 66% for CH, odds ratio with 95% confidence intervals 4.04 [1.3-12.6], P = 0.018). The median [95% CI)] time to successful testing start was shorter (25 [20-29] min vs 30 [20-49] min for IN DEX and CH, respectively, log rank test P = 0.02) and the proportion of children whose parents reported a return to baseline activity on the day of testing was greater for the IN DEX than the CH group (89% vs 64%, OR [95% CI] 4.71 [1.34-16.6], P = 0.02). There were no major adverse events in either group and no significant differences in the incidence of minor events. CONCLUSION: Intranasal dexmedetomidine is an effective alternative to oral chloral hydrate sedation for ABR testing, with the advantages of a higher incidence of testing completion with a single dose, shorter time to desired sedation level, and with significantly more patients reported to return to baseline activity on the same day. PMID- 26814039 TI - The addition of clonidine to bupivacaine in saphenous/sciatic nerve blocks in children. PMID- 26814040 TI - Inadvertent insertion of central venous catheter into a Blalock-Taussig shunt--a rare complication. PMID- 26814041 TI - Anesthesia for noncardiac intervention in a patient with total anomalous systemic venous return. PMID- 26814042 TI - Routine epidurography for epidural placement in anesthetized pediatric patients. PMID- 26814043 TI - Letter to the Editor informing readers about a free patient information animation. PMID- 26814044 TI - A retrospective evaluation of fistula formation in children undergoing hypospadias repair and caudal anesthesia. PMID- 26814045 TI - Rapid ester biosynthesis screening reveals a high activity alcohol-O acyltransferase (AATase) from tomato fruit. AB - Ethyl and acetate esters are naturally produced in various yeasts, plants, and bacteria. The biosynthetic pathways that produce these esters share a common reaction step, the condensation of acetyl/acyl-CoA with an alcohol by alcohol-O acetyl/acyltransferase (AATase). Recent metabolic engineering efforts exploit AATase activity to produce fatty acid ethyl esters as potential diesel fuel replacements as well as short- and medium-chain volatile esters as fragrance and flavor compounds. These efforts have been limited by the lack of a rapid screen to quantify ester biosynthesis. Enzyme engineering efforts have also been limited by the lack of a high throughput screen for AATase activity. Here, we developed a high throughput assay for AATase activity and used this assay to discover a high activity AATase from tomato fruit, Solanum lycopersicum (Atf-S.l). Atf1-S.l exhibited broad specificity towards acyl-CoAs with chain length from C4 to C10 and was specific towards 1-pentanol. The AATase screen also revealed new acyl-CoA substrate specificities for Atf1, Atf2, Eht1, and Eeb1 from Saccharomyces cerevisiae, and Atf-C.m from melon fruit, Cucumis melo, thus increasing the pool of characterized AATases that can be used in ester biosynthesis of ester-based fragrance and flavor compounds as well as fatty acid ethyl ester biofuels. PMID- 26814046 TI - New guidelines for HER2 pathological diagnostics in gastric cancer. PMID- 26814047 TI - Current status of the histopathological assessment, diagnosis, and reporting of colorectal neuroendocrine tumors: A Web survey from the Japanese Society for Cancer of Colon and Rectum. AB - Although new classifications for neuroendocrine tumors were established by the World Health Organization, the current procedures and terms used in pathology laboratories are not known. A Web-based questionnaire was distributed to 491 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum, and 150 participated. The questionnaires included questions regarding routine pathological reporting, staining, and assessment of neuroendocrine tumors. Next, the time taken to assess Ki-67 index and mitotic count according to recommendation was evaluated to determine its feasibility. Most laboratories recorded diagnostic term, depth of invasion, size, lymph-vascular invasion, Ki-67 index, and mitotic count. However, only 32.2% reported tumor stage. Chromogranin A and synaptophysin were common neuroendocrine markers. D2-40 and elastica stain were frequently used to confirm lymph-vascular invasion. Only 62.1% counted more than 500 cells for the Ki-67 index, and only 17.0% counted more than 50 fields for the mitotic count, as suggested by the recommendations. Median time of 7 cases was 18.0 and 27.3 min to assess mitotic count in 50 fields with Ki-67 index in 500 and 2000 cells, respectively. For more standardized pathological reporting, education about standardized staging systems are needed in Japan. Practical and standardized procedures for mitotic index and Ki-67 index are also required. PMID- 26814048 TI - Functionalized silk assembled from a recombinant spider silk fusion protein (Z 4RepCT) produced in the methylotrophic yeast Pichia pastoris. AB - Functional biological materials are a growing research area with potential applicability in medicine and biotechnology. Using genetic engineering, the possibility to introduce additional functions into spider silk-based materials has been realized. Recently, a recombinant spider silk fusion protein, Z-4RepCT, was produced intracellularly in Escherichia coli and could after purification self-assemble into silk-like fibers with ability to bind antibodies via the IgG binding Z domain. In this study, the use of the methylotrophic yeast Pichia pastoris for production of Z-4RepCT has been investigated. Temperature, pH and production time were influencing the amount of soluble Z-4RepCT retrieved from the extracellular fraction. Purification of secreted Z-4RepCT resulted in a mixture of full-length and degraded silk proteins that failed to self-assemble into fibers. A position in the C-terminal domain of 4RepCT was identified as being subjected to proteolytic cleavage by proteases in the Pichia culture supernatant. Moreover, the C-terminal domain was subjected to glycosylation during production in P. pastoris. These observed alterations of the CT domain are suggested to contribute to the failure in fiber assembly. As alternative approach, Z-4RepCT retrieved from the intracellular fraction, which was less degraded, was used and shown to retain ability to assemble into silk-like fibers after enzymatic deglycosylation. PMID- 26814049 TI - High-throughput cell quantification assays for use in cell purification development - enabling technologies for cell production. AB - High-throughput screening (HTS) technology is gaining increasing importance in downstream process development of cell-based products. The development of such HTS-technologies, however, is highly dependent on the availability of robust, accurate, and sensitive high-throughput cell quantification methods. In this article, we compare state-of-the-art cell quantification methods with focus on their applicability in HTS-platforms for downstream processing of cell-based products. Sensitivity, dynamic range, and precision were evaluated for four methods that differ in their respective mechanism. In addition, we evaluated the performance of these methods over a range of buffer compositions, medium densities, and viscosities, representing conditions found in many downstream processing methods. We found that CellTiter-GloTM and flow cytometry are excellent tools for high-throughput cell quantification. Both methods have broad working ranges (3-4 log) and performed well over a wide range of buffer compositions. In comparison, CyQuant(r) Direct and CellTrackerTM had smaller working ranges and were more sensitive to changes in buffer composition. For fast and sensitive quantification of a single cell type, CellTiter-GloTM performed best, while for more complex cell mixtures flow cytometry is the method of choice. Our analysis will facilitate the selection of the most suitable method for a specific application and provides a benchmark for future HTS development in downstream processing of cell-based products. PMID- 26814050 TI - Variation in intraoperative and postoperative red blood cell transfusion in pediatric surgery. AB - BACKGROUND: Intraoperative and postoperative red blood cell (RBC) transfusions are relatively frequent events tracked in the American College of Surgeons' National Surgical Quality Improvement Program-Pediatric (ACS-NSQIP-P). This study sought to quantify variation in RBC transfusion practices among hospitals. STUDY DESIGN AND METHODS: This is an observational study of children older than 28 days who underwent a general, neurologic, urologic, otolaryngologic, plastic, or orthopedic operation at 50 hospitals in participating in the ACS-NSQIP-P during 2011 to 2012. The primary outcome was whether or not a RBC transfusion was administered from incision time to 72 hours postoperatively. Transfusions of fresh-frozen plasma, cryoprecipitate, and platelets were excluded from data abstraction due the rarity of their administration. A multivariate hierarchical risk-adjustment model estimated the risk-adjusted hospital RBC transfusion odds ratio (OR) and designated hospitals by transfusion practice. RESULTS: The mean RBC transfusion rate was 1.5%. Five preoperative variables were associated with greater than threefold increased odds of having an intraoperative or postoperative RBC transfusion; young age; 29 days to 1 year (OR, 5.9; p < 0.001) and 1 to 2 years (OR, 3.4; p < 0.001); American Society of Anesthesiologists Class IV (OR, 3.2; p < 0.001); procedure linear risk (OR, 3.1; p < 0.001); preoperative septic shock (OR, 14.5; p < 0.001); and preoperative cardiopulmonary resuscitation (OR, 8.1; p < 0.001). Twenty-five hospitals had RBC transfusion practices significantly different than risk-adjusted mean (17 higher and eight lower). CONCLUSION: Intraoperative and postoperative RBC transfusion practices vary widely among hospitals after controlling for patient and procedural characteristics. PMID- 26814052 TI - Comparison of the validity of two dental age estimation methods: A study on South Indian population. AB - BACKGROUND: Forensic odontologists are often confronted with the problem of estimating age for the identification of unknown bodies or skeletal remains of accidents, crimes and disaster victims. Teeth have the benefit of being preserved long after other tissues have disintegrated and present the only means for age estimation. Different techniques have been published for dental age estimation with variable accuracy, precision and reliability. The search for optimal method by forensic odontologists has continued over the years until the present day. AIM: The present study was aimed at evaluating and comparing the accuracy of age estimation using translucent dentin and cemental annulations. MATERIALS AND METHODS: A total of 150 freshly extracted teeth were obtained and longitudinal ground sections were prepared. The length of the translucent dentin was measured and cemental annulations were counted in each section and the age was calculated separately for both the methods. RESULTS AND CONCLUSION: The present study suggests that both the methods are reliable in the middle age groups; whereas the large error obtained in the extreme age groups indicate that translucent dentin method should be preferred in older age group and cemental annulations method in the younger age group before the formation of translucent dentin. PMID- 26814051 TI - Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications. AB - During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co expression may refine their properties rather than determine their identity. Gain and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features. PMID- 26814053 TI - Age estimation in Indian children and adolescents in the NCR region of Haryana: A comparative study. AB - INTRODUCTION: Age estimation is a preliminary step in the identification of an individual. It is a crucial and often most critical step for forensic experts. The assessment has been standardized utilizing common dental diagnostic x-rays, but most such age-estimating systems are European population-based and their applicability has not been determined in the context of the Indian population. AIMS AND OBJECTIVES: To assess the applicability and to compare the methods of dental age estimation by Demirjian's method and the same method as modified by Willems (i.e. the Willems method) in Indian children of the National Capital Region (NCR). Also, to find a correlation among skeletal maturity using the Cervical vertebrae maturation index (CVMI), dental maturity, and chronological age in the same population. MATERIALS AND METHODS: This cross-sectional study was conducted using dental radiographs of 70 orthodontic patients (37 males, 33 females) in the age range 9-16 years selected by simple random sampling. pantomogram were used to estimate dental age by Demirjian's method and the Willems method using their scoring tables. Lateral cephalograms were used to estimate skeletal maturity using CVMI. The latter was compared with Demirjian's stage for mandibular left second molar. RESULTS: Overestimation of age among males by 0.856 years and 0.496 years was found by Demirjian's and the Willems methods, respectively. Among females, both the methods underestimated the age by 0.31 years and 0.45 years, respectively. Demirjian's stage G corresponded to CVMI stage 3 in males and stage 2 in females. CONCLUSION: In our study, the Willems method has proved to be more accurate for age estimation among Indian males, and Demirjian's method for Indian females. A statistically significant association appeared between Demirjian's stages and CVMI among both males and females. Our study recommends the derivation of a regression formula by studying a larger section of the Indian population instead of applying the European system of age estimation directly to the Indian scenario. PMID- 26814054 TI - Congenital Pouch Colon associated with Pseudoexstrophy: Report of Two Cases. AB - This report describes two newborn girls with single perineal opening (cloaca), and pseudoexstrophy in the form of divergent pubic bones and rectus muscles, and a low-set umbilicus. Both patients had a type II congenital pouch colon (CPC) with one hemiuterus and vagina on each side in the pelvis. In one patient, a Meckel's diverticulum was present 5 cm from the ileocecal junction. In both girls, a diverting proximal ileostomy was the initial surgery. PMID- 26814055 TI - Passiflora incarnata L. Improves Spatial Memory, Reduces Stress, and Affects Neurotransmission in Rats. AB - Passiflora incarnata L. has been used as a medicinal plant in South America and Europe since the 16th century. Previous pharmacological studies focused mainly on the plant's sedative, anxiolytic, and anticonvulsant effects on the central nervous system and its supporting role in the treatment of addiction. The aim of the present study was to evaluate the behavioral and neurochemical effects of long-term oral administration of P. incarnata. The passionflower extract (30, 100, or 300 mg/kg body weight/day) was given to 4-week-old male Wistar rats via their drinking water. Tests were conducted after 7 weeks of treatment. Spatial memory was assessed in a water maze, and the levels of amino acids, monoamines, and their metabolites were evaluated in select brain regions by high performance liquid chromatography (HPLC). We observed reduced anxiety and dose-dependent improvement of memory in rats given passionflower compared to the control group. In addition, hippocampal glutamic acid and cortical serotonin content were depleted, with increased levels of metabolites and increased turnover. Thus, our results partially confirmed the proposed mechanism of action of P. incarnata involving GABAA receptors. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26814056 TI - Novel 20(S)-sulfonylamidine derivatives of camptothecin and the use thereof as a potent antitumor agent: a patent evaluation of WO2015048365 (A1). AB - A series of camptothecin (CPT) derivatives featuring acyl-esterification of the 20(S)-hydroxyl group with a residue containing a sulfonylamidine moiety is synthesized via a Cu catalyzed three-component reaction. The compounds show remarkable cytotoxicity against a panel of tumor cells, including a cell line exhibiting Multi-Drug Resistant (MDR) phenotype. The patent develops 9a, the best derivative of the series, that i) selectively poisons DNA Topoisomerase I (TopoI); ii) induces cell-cycle S-phase arrest with activation of the DNA damage response pathway and apoptosis induction and iii) shows considerable in vivo antitumor potency. We envision that the peculiar modification of the 20(S) hydroxyl group of CPT with a sulfonylamidine residue will play a continuing role in affording new TopoI poison drug candidates for therapeutic applications. PMID- 26814057 TI - Non-ECG-gated CT pulmonary angiography and the prediction of right ventricular dysfunction in patients suspected of pulmonary embolism. AB - PURPOSE: Right ventricular dysfunction (RVD) is an important prognostic factor of 30-day mortality in patients with acute pulmonary embolism (PE). The aim of our study was to evaluate whether non-electrocardiogram (ECG)-gated cardiovascular parameters attained during computed tomography pulmonary angiography (CTPA) could predict RVD in patients suspected of PE using ECG-gated cardiac CT angiography as reference. METHODS: Consecutive patients suspected of PE were referred to a ventilation/perfusion single-photon emission tomography (V/Q-SPECT) as first-line imaging procedure. Patients had a V/Q-SPECT/CT, a CTPA and an ECG-gated cardiac CT angiography performed the same day. RESULTS: A total of 71 patients were available for analysis. Seventeen patients (24%) had RVD. The non-ECG-gated dimensions of left and right ventricle and the major vessels were correlated with ECG-gated cardiac dimensions. The size of the pulmonary trunk could identify patients with RVD: AUC (0.67, 95% confidence intervals (CIs) 0.52-0.82) as seen in the ROC curve (P<0.05). With a cut-off value of the pulmonary trunk of 29 mm, the sensitivity and specificity were 70.6% and 55.5%, respectively. The positive predictive and negative predictive values for detection of RVD were 59.1% and 85.7%, respectively. CONCLUSION: In the present study, we demonstrated correlation between ECG-gated cardiac dimensions and non-ECG-gated cardiovascular parameters, however with only moderate diagnostic accuracies. We demonstrated that the dimension of the pulmonary trunk might be of value in detection of patients with RVD. We suggest further studies on the potential value of non-ECG gated cardiac dimensions in patients suspected of PE. PMID- 26814058 TI - Activation of Cellular Immunity in Herpes Simplex Virus Type 1-Infected Mice by the Oral Administration of Aqueous Extract of Moringa oleifera Lam. Leaves. AB - Moringa oleifera Lam. is used as a nutritive vegetable and spice. Its ethanol extract has been previously shown to be significantly effective in alleviating herpetic skin lesions in mice. In this study, we evaluated the alleviation by the aqueous extract (AqMOL) and assessed the mode of its anti-herpetic action in a murine cutaneous herpes simplex virus type 1 (HSV-1) infection model. AqMOL (300 mg/kg) was administered orally to HSV-1-infected mice three times daily on days 0 to 5 after infection. AqMOL significantly limited the development of herpetic skin lesions and reduced virus titers in the brain on day 4 without toxicity. Delayed-type hypersensitivity (DTH) reaction to inactivated HSV-1 antigen was significantly stronger in infected mice administered AqMOL and AqMOL augmented interferon (IFN)-gamma production by HSV-1 antigen from splenocytes of HSV-1 infected mice at 4 days post-infection. AqMOL administration was effective in elevating the ratio of CD11b(+) and CD49b(+) subpopulations of splenocytes in infected mice. As DTH is a major host defense mechanism for intradermal HSV infection, augmentation of the DTH response by AqMOL may contribute to their efficacies against HSV-1 infection. These results provided an important insights into the mechanism by which AqMOL activates cellular immunity. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26814059 TI - Impact of dynamic changes in MELD score on survival after liver transplantation - a Eurotransplant registry analysis. AB - BACKGROUND & AIMS: With restricted numbers of available organs, futility in liver transplantation has to be avoided. The concept of dynamic changes in MELD score (DeltaMELD) has previously been shown to be a simple tool to identify patients with the greatest risk of death after transplantation. Aim was to validate this concept with the Eurotransplant (ET) database. METHODS: A retrospective registry analysis was performed on all patients listed for liver transplantation within ET between 2006 and 2011. Patients <18 years of age, acute liver failure, malignancy and patients listed for retransplantation were excluded. Influence of MELD at listing (MELDon), MELD at transplantation (MELDoff), DeltaMELD, age, sex, underlying disease and time on the waiting list on overall survival after liver transplantation were evaluated. RESULTS: A total of 16 821 patients were listed for liver transplantation, 8096 met the inclusion criteria. Age, MELD on and DeltaMELD showed significant influence on survival on the waiting list. Age and DeltaMELD showed influence on survival after liver transplantation, with DeltaMELD>10 showing a 1.6-fold increased risk of death. CONCLUSION: The concept of DeltaMELD was validated in a large, prospective data set. It provides a simple tool to identify patients with increased risk of death after liver transplantation and might help improve long-term results. PMID- 26814060 TI - [Improve the standardized diagnosis and treatment of male infertility: a brief analysis of the noval trichotomy approach]. PMID- 26814061 TI - [New guidelines for molecular diagnosis of Y-chromosomal microdeletions in Europe]. PMID- 26814062 TI - [Recognition of varicocelectomy]. PMID- 26814063 TI - [Correlation between chromosomal polymorphisms and male sperm quality in population of Jilin Province]. AB - OBJECTIVE: To evaluate the correlation between chromosomal polymorphisms and male sperm quality in Jilin Province. METHODS: A total of 2 584 male patients with infertility in Center for Reproductive Medicine, First Bethune Hospital of Jilin University from 2008 to 2013 were enrolled, which semen analysis, chromosomal analysis, Y chromosome microdeletion analysis and serum hormone levels analysis were performed. A total of 602 healthy individuals, 50 fertile individuals with normal kayrotypes, 50 azoospermia patients with normal kayrotypes and 50 oligospermia patients with normal kayrotypes were selected as control groups. RESULTS: There was no significant difference in the frequency of chromosome polymorphisms between infertile patients and normal control individuals (3.91% (101/2 584) vs 3.16% (19/602), P > 0.05). And there was no significant difference in the frequency of autosomal polymorphisms between infertile patients and normal control individuals (all P > 0.05). The frequency of Yqh-variant was increased by the decrease of sperm count and it appeared a significantly high frequency in azoospermia patients compared with oligospermia patients and sperm count normal patients in the infertile group (57.14% (21/42) vs 24.32% (9/37), 0 (0/13), both P < 0.05). There was no significant difference in the testis volume and serum hormone levels between the infertile patients with chromosomal polymorphisms and patients in control groups with normal kayrotypes (all P > 0.05). The results of PCR amplication indicated that 32.14% (9/28) patients with Yqh +/- had Y chromosome microdeletion. CONCLUSIONS: There is no significant correlation between autosomal polymorphisms and male infertility. But Yqh +/- may be responsible for Y chromosome microdeletion and male infertility. PMID- 26814064 TI - [Efficacy and safety of microsurgical varicocelectomy combined with aescine in the treatment of varicocele]. AB - OBJECTIVE: To discuss the efficacy and safety of microsurgical varicocelectomy combined with aescine in the treatment of varicocele. METHODS: A total of 120 patients with varicocele received treatments and follow up in Shanghai Renji Hospital and Shanghai General Hospital between September 2013 and April 2015, 63 patients of which were infertile and 57 patients of which were painful varicocele. A total of 106 patients were unilateral varicocele and 14 patients were bilateral varicocele. Forty-one patients were treated with varicocelectomy, and 79 patients were treated with varicocelectomy combined with aescine, 300 mg, twice a day, orally. Sperm analysis, pregnancy rate, sex hormone, and complications were recorded after six months treatments. RESULTS: There was significant difference in the sperm motility improvement in infertile patients between microsurgical group (60.0%, 12/20) and combined therapy group (83.7%, 36/43) (P < 0.05). There was no significant difference in levels of sexual hormones in infertile patients between microsurgical group and combined therapy group (luteinizing hormone (4.07 +/- 1.49) vs (4.29 +/- 1.32) U/L, follicule stimulating hormone (5.64 +/- 2.70) vs (5.11 +/- 1.25) U/L, and testosterone (16.09 +/- 2.25) vs (15.98 +/- 3.79) ug/L). The pregnancy rate of infertile patients in microsurgical group and combined therapy group were 15.0% (3/20) and 18.6% (8/43), respectively, with no statistic difference between these two groups (P > 0.05). The total improvement rates for the pain resolution in microsurgical group and combined therapy group were 76.2% (16/21) and 94.4% (34/36), respectively, with statistic difference between these two groups (P < 0.05). In the microsurgical group, there were two cases of scrotal edema and one case of reoccurrence after treatment, while no complications were appeared in the combined therapy group. CONCLUSIONS: Microsurgical varicocelectomy combined with aescine could improve sperm quality, relieve pain, and prevent complications occurrence to some extent compared with microsurgical varicocelectomy. Microsurgical varicocelectomy combined with aescine could be applied in clinical varicocele treatment. PMID- 26814065 TI - [Detection of promoter region of CFTR gene in Chinese congenital bilateral absence of vas deferens]. AB - OBJECTIVE: To detect the variants in the promoter region of the CFTR gene in congenital bilateral absence of vas deferens (CBAVD). METHODS: A total of 11 CBAVD patients and 50 healthy men as control were enrolled in the study from May 2013 to January 2015. Sanger sequencing was performed in the promoter region of 3.8 kb of the CFTR gene on the PCR products. The genome sequence of the CFTR gene was compared and analyzed with the website of NCBI and Cystic Fibrosis Mutation Database. Also, Transfac and phylogenetic footprinting method was used to investigate the relationship between the promoter region variants and the transcription factors function components. RESULTS: SNP of c.-8G > C (n = 1) and c.-966T > G (n = 7), as well as one single nucleotide variant of c.-195C > A (n = 1) were identified in the promoter region of the CBAVD patients, of which c.-195C > A was in the conserved domains of the promoter region. CONCLUSIONS: A single nucleotide variant within the conserved region of CFTR promoter is detected in Chinese CBAVD. And further functional study should be performed to explore the relationship between the variants in CFTR promoter and Chinese CBAVD. PMID- 26814066 TI - [Evaluation of left atrial function by three-dimensional speckle-tracking echocardiography in heart failure with preserved ejection fraction patients]. AB - OBJECTIVE: To evaluate left atrial function changes inheart failure with preserved ejection fraction (HFpEF) patients by three-dimensional speckle tracking echocardiography (3D-STE) and Real time three-dimensional echocardiograph (RT3DE). METHODS: 43 HFpEF patients and a control group with 18 healthy subjectswere enrolled. According to left atrial max volume index (LAVImax), patients were grouped as A (LAVImax < 34 ml/m2) and B (LAVImax >= 34 ml/m(2)). 3D-STE deformative parameters, left atrial ventricular-systolic longitudinal peak strain (LSs%) and left atrial pre-contraction longitudinal peak strain (LSa%), from three levels (Basal, Middle and Roof) and global were measured. These parameters combined with RT3DE and Doppler parameters were analyzed between groups. RESULTS: Reproducibilities of MLSs and MLSa were satisfactory (ICC > 0.8). In group A, LA filling and emptying deformation reduced mainly in middle level (compared to control group: MLSs (33 +/- 6)% vs (45 +/- 9)%, MLSa (12 +/- 3)% vs (17 +/- 5)%, P < 0.05), while in group B, deformation of basal and roof levels also reduced (compared to A and control group: BLSs (18 +/- 7)% vs (25 +/- 8)% vs (29 +/- 8)%, RLSs (24 +/- 9)% vs (28 +/- 8)% vs (32 +/- 10)%; compared to control group: BLSa (11 +/- 5)% vs (14 +/- 4)%, RLSa (12 +/- 5)% vs (15 +/- 5)%; all P < 0.05). LA stiffness increased while LA expansion index (LAEI%), LA passive ejection fraction (LAPEF%) decreased significantly in HFpEF patients, LA active ejection fraction (LAAEF%) of group B also decreased. CONCLUSIONS: 3D-STE in combination with RT3DE enables the assessment of LA function effectively and comprehensively. 3D-STE strains of LA middle level were ideal parameters for LA function assessment. HFpEF patients have significantly reduced LA reservoir, conduit, pump function and left ventricular diastolic dysfunction, and these changes were more apparent in patients with LA enlarged significantly. PMID- 26814067 TI - [Influence of environmental factors on the migratory birds population with chronic obstructive pulmonary disease]. AB - OBJECTIVE: To explore the influence of environment factors on the migratory birds population with chronic obstructive pulmonary disease (MDCOPD). METHODS: A total of 82 stable MDCOPD patients from Beijing area, who went to Hainan Branch of PLA General Hospital and the People's Hospital of Sanya for treatment between September 2012 and May 2014, were recruited in this study.At Sanya, from October to April of the following year (wintertime), all the patients were evaluated by COPD assessment test (CAT) and modified medical research council (mMRC) questionnaire, and follow-up was performed every 2 months.From May to September (summertime), when the MDCOPD patients came back to Beijing area, the patients were evaluated by CAT and mMRC questionnaire again, and still follow-up was performed every 2 months.The scores of before and after living environment changed were compared.Acute exacerbations or hospitalizations were recorded if any occurred in the patients during the follow up period, and the patients were reevaluated by the two questionnaires 1 month later after they became stable.At the same time, the daily air quality index (AQI) from the national urban air quality publishing platform and the temperature and relative humidity from the local weather network were recorded. RESULTS: The score of CAT in Sanya was significantly lower than that in Beijing ((20.0 +/- 8.0) vs (26.4 +/- 7.1) scores, P < 0.001); the score of mMRC in Sanya was also significantly lower than Beijing ((1.9 +/- 0.8) vs (2.9 +/- 0.9) scores, P = 0.001). Based on the latest guidelines, the classification of COPD patients changed from D (in Beijing) to C (in Sanya) according to mMRC scores, while the CAT scores from the two cities did not cause the change of classification.The difference of temperature between wintertime of Sanya and summertime of Beijing was not significant ((23.1 +/- 4.2) vs (24.3 +/- 2.3) degrees C, P = 0.674); the wintertime's AQI in Sanya was significantly lower than the summertime's AQI in Beijing ((49.4 +/- 8.9) vs (113.1 +/- 14.2) ug/m3, P < 0.001); the relative humidity of wintertime in Sanya was significantly higher than that of summertime in Beijing ((90.6 +/- 4.9)% vs ((58.0 +/- 10.0)%, P = 0.001). CONCLUSION: When the MDCOPDs live in the area where has a better air quality and higher relative humidity, their quality of life and activity tolerance can be improved obviously. PMID- 26814069 TI - [Efficacy of pressure support ventilation general anesthesia in infants and premature patients undergoing ophthalmologic surgeries]. AB - OBJECTIVE: To investigate the efficacy of pressure support ventilation (PSV) general anesthesia in infants and premature patients undergoing ophthalmologic surgeries. METHODS: A total of forty-two infants undergoing vitreoretinal surgeries in Peking university people's hospital from Dec. 2014 to Jul. 2015 were enrolled in the study, whose post-conceptual age (PCA, duration from the mother's last menstrual period to the date surgery was performed) were 38-92 weeks. They were divided into 3 groups according to PCA, which were group A (PCA <= 44 weeks), group B (44 weeks < PCA <= 64 weeks) and group C (64 weeks < PCA <= 92 weeks). Anesthesia was induced with 6% sevoflurane inhalation by mask. After placement of laryngeal mask airway, patients were breathing spontaneously during the whole procedure with the inhalational maintenance concentration of sevoflurane and ventilation parameters adjusted according to clinical set. The surgical procedure begun when satisfying retrobulbar nerve block was achieved. The end-tidal concentration- of sevoflurane, hemodynamic and respirational data were recorded at the time of before surgery (T0), 15 minutes after surgery (T1) and 30 minutes after surgery (T2). The time interval from cease of sevoflurane inhalation to the laryngeal mask removal and adverse events during and after surgery were also recorded. RESULTS: A total of 42 patients were enrolled in the study, with 10 cases in group A, 17 cases in group B and 15 cases in group C. The hemodynamics of all patients in three groups were stable. There was no significant difference in removal time interval among groups (all P > 0.05). No significant difference was found in end-tidal concentrations of sevoflurane, minute ventilation, pressure of end-tidal carbon dioxide, lung compliance among three time points(all P > 0.05). The respiration rate (per minute) of group B and group C were (33.1 +/- 5.7) and (29.4 +/- 6.4) at T1, (35.8 +/- 7.4) and (32.1 +/ 5.6) at T0, respectively, with statistical difference (F = 5.087, 5.628; P < 0.05) at both time points between groups. The peak airway pressure (cmH2O) of group B and group C were (14.5 +/- 3.1) and (14.3 +/- 2.2) at T1, (14.1 +/- 2.9) and (13.1 +/- 1.5) at T0, respectively, with statistical difference (F = 4.923, 12.393; P < 0.05) at both time points between groups. There was no significant difference in end-tidal concentrations of sevoflurane, pressure of end-tidal carbon dioxide, expiratory tidal volume per kg, minute ventilation per kg, respiration rate and peak airway pressure among groups (all P > 0.05). There was no severe adverse events during and after surgery in any group. CONCLUSION: The application of PSV during laryngeal mask airway general anesthesia with spontaneous breathing maintained can be a choice for infants and premature patients undergoing ophthalmologic surgeries. PMID- 26814068 TI - [Relationship between 24-hour urinary sodium and renin-angiotensin-aldosterone system in children with postural tachycardia syndrome]. AB - OBJECTIVE: To analyze the relationship between 24 hours urinary sodium and renin angiotensin-aldosterone system (RAAS) in children with postural tachycardia syndrome (POTS) and to explore low blood volume related pathogenesis of POTS. METHODS: A total of 39 POTS children who were at the clinic or admitted to the Department of Pediatrics, Peking University First Hospital from June 2012 to February 2013 and 21 healthy children (control group) were enrolled, level of RAAS in plasma, 24-hour urinary sodium and plasma sodium were detected, respectively. Baseline data, levels of RAAS and hemodynamic parameters were compared between POTS and control group, as well as groups with different 24-hour urinary sodium levels of POTS. RESULTS: The angiotensin II levels of POTS children were significantly higher than that of control group ((105 +/- 50) vs (84 +/- 28) ng/L, P = 0.041), while no statistical significance was found in plasma renin and aldosterone (P > 0.05). Pearson correlation analysis showed that 24-hour urinary sodium and angiotensin II in children with POTS was negatively correlated (r = -0.536, P < 0.001). Angiotensin II, symptom score, upright heart rate and changes of heart rate were significantly higher in urinary sodium < 124 mmol/24 h group than that in urinary sodium >= 124 mmol/24 h group (P < 0.05). CONCLUSION: The regulating function disorder of RAAS may involve in the pathogenesis of POTS and cause sustained low blood volume in patients with POTS. PMID- 26814070 TI - [Characteristic of blood pressure profile in elderly hypertensive patients with chronic kidney disease: a tertiary hospital-based study]. AB - OBJECTIVE: To identify the characteristics of blood pressure (BP) in the elderly hypertensive patients with chronic kidney disease (CKD). METHODS: We retrospectively recruited 337 CKD patients who had been admitted into our renal unit during January 2010 to December 2012 and undergone clinical blood pressure (CBP) and ambulatory blood pressure (ABP) measurement with detailed clinical data. Those with age >= 60 years old (n = 94) were designated as elderly patients and their BP data were compared with those of young- and middle-aged patients (< 60 years old, n = 243). Logistic regression was adopted to analyze the independent risk factor for white-coat hypertension and reverse-dipper rhythm. RESULTS: Compared to those < 60 y, the elder CKD patients had the following characteristics: (1) Higher prevalence of white-coat hypertension (24.5% vs 12.3%, P = 0.008). (2) Significantly lower diastolic blood pressure of average 24 h, daytime and nighttime by ambulatory monitoring of blood pressure (ABPM) (all P < 0.001). (3) Higher BP variability with significant difference (all P < 0.05) and more patients with morning surge (11.7% vs 3.7%, P = 0.009). (4) Higher prevalence of reverse-dipper circadian BP rhythm (41.5% vs 25.1%, P = 0.004). (5) Age was an independent predictor for white-coat hypertension (OR = 1.024, 95% CI: 1.004-1.044) and reverse-dipper circadian BP rhythm (OR = 1.016, 95% CI: 1.001 1.032). CONCLUSIONS: The BP profile of elderly hypertensive CKD patients is different from that of young- and middle-aged patients. ABPM should be more commonly performed to improve BP treatment of elderly CKD patients. PMID- 26814071 TI - [Training evaluation of clinical laboratory excellence for technologists from some county and township hospitals in 31 provinces of China]. AB - OBJECTIVE: To improve clinical testing excellence through a large scale training project targeting laboratory operators at China's county and township hospitals. METHODS: The Chinese Society of Laboratory Medicine launched the "Clinical Laboratory Standards and Training Support Project" from 2010 to 2013. The project innovatively created a model of partnership between government, professional association, individual hospitals and other social forces. A survey before training was conducted in 445 county-hospital laboratories in 31 provinces. Six months after implementation, a sampling survey was conducted among 250 participating county hospitals in 9 provinces to assess the project. RESULTS: From 2010 to 2013, the project had covered 31 provinces of China, and trained technologists from 3 570 hospitals. After training, the average pass rate of assessment examination increased to 83.7% compared with 16.2% before the training. 29.6% hospitals added new biochemistry parameters, and the number of hospital with new hematology, immunology, and microbiology parameters accounted for 24.4%, 21.2% and 16.4%, respectively. The internal quality control and external quality assessment items also increased significantly. Biochemistry increased most, reaching 12.8% and 10.0%, and microbiology also reached 4.4% and 2.8% respectively. Bio-safety management capacities were also enhanced. The number of hospital implementing bio-safety risk assessment increased from 41.2% to 76.4%. CONCLUSIONS: This project helpfully fills an important technical gap of clinical testing in China's rural healthcare infrastructure. Through training, clinical laboratory operations has been standardized, and systems of internal quality control and external quality assessment are increasingly improved. PMID- 26814072 TI - [Effect of lung strain on pulmonary edema in dogs with acute respiratory distress syndrome]. AB - OBJECTIVE: To explore the effect of lung strain on pulmonary edema in dogs with acute respiratory distress syndrome (ARDS) preliminarily. METHODS: Twenty dogs were recruited to induct ARDS models by venous injection of oleic acid and grouped into Group S1.0, S1.5, S2.0, S2.5 randomly, the lung strain was previously designated as 1.0, 1.5, 2.0 or 2.5 for each group. The ventilation was used to support the dogs for 24 hours with tidal volume calculated from lung strain, functional residual capacity and the volume recruitment by positive end expiratory pressure. Extra vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were tested by thermodilution technique and wet to dry ratio of lung tissue was evaluated by weighing method. RESULTS: The tidal volume of Group S1.0, S1.5, S2.0, S2.5 was (7.5 +/- 1.7), (13.9 +/- 5.8), (17.9 +/- 4.7) and (20.3 +/- 7.9) ml/kg, respectively. After ventilation for 4 h, EVLWI in Group S2.0 and Group S2.5 were higher than them in Group S1.0 and Group S1.5 ((38.9 +/- 6.5), (40.1 +/- 7.7) vs (26.6 +/- 5.2), (28.8 +/- 5.4) ml/kg; F = 5.627, P = 0.009). At the end of study, PVPI of Group S2.5 increased significantly versus Group S1.0, S1.5 and S2.0 (16.7 +/- 5.4 vs 7.0 +/- 2.3, 9.2 +/- 2.2, 11.5 +/- 6.0; F = 4.329, P = 0.022). Wet to dry ratios of lung tissue in Group S2.0 and Group S2.5 were significantly higher than Group S1.0 and Group S1.5 (10.4 +/- 1.2, 10.8 +/- 1.5 vs 8.3 +/- 1.2, 8.0 +/- 2.2; F = 5.627, P = 0.009) after ventilation. CONCLUSION: Lung strain above 2.0 aggravates pulmonary edema dramatically and the effect might be slight if lung strain was smaller than 1.5. PMID- 26814073 TI - [Protective effect of ulinastatin on cerebral tissue in rats with lethal scald injury]. AB - OBJECTIVE: To explore the protective effects of ulinastatin on cerebral tissue in rats following lethal burn injury and its relationship with the expression of protective protein. METHODS: A total of 40 male Sprague-Dawley rats were randomly divided into scald and ulinastatin groups (n = 20 each). Both groups were subjected to 50% total body surface area third-degree burns. Immediately after scalding, 1 ml normal saline was injected intravenously in scald group while 1 ml saline containing ulinastatin (40 000 U/kg) in ulinastatin group. Then cerebral tissue was harvested for measuring the activities of neuron-specific enolase (NSE) by enzyme-linked immunosorbent assay (ELISA) at 6 h and 24 h post-injury. And the level of acetylated histone H3 was detected by Western blot and heat shock protein 70 (HSP70) by ELISA. The rates of tissue water content in heart were determined by dry/wet weight. RESULTS: NSE and water content of cerebral tissue after 6 h injury in ulinastatin group were significantly lower than those in scald group ((146 +/- 11) vs (156 +/- 13) pg/ml, (77.3 +/- 1.9)% vs (79.0 +/- 2.2)%, both P < 0.05), the expressions of HSP70 and histone H3 after 6 h injury in ulinastatin group was significantly higher than those in scald group ((99 +/- 19) vs (92 +/- 13) pg/ml, (1.26 +/- 0.37) vs (0.57 +/- 0.23), both P < 0.05). The NSE content of cerebral tissue after 24 h injury in ulinastatin group was significantly lower than that in scald group ((141 +/- 14) vs (159 +/- 10) pg/ml, P < 0.05). And the water content of cerebral tissue, the expressions of HSP70 and histone H3 after 24 h injury had no significant inter-group differences ((75.9 +/ 1.2)% vs (76.5 +/- 1.4)%, (118 +/- 17) vs (102 +/- 16) pg/ml, (2.31 +/- 0.27) vs (1.87 +/- 0.31), both P > 0.05). CONCLUSIONS: Ulinastatin significantly alleviates cerebral tissue injury in early stage of burn injury. And its protective effects may be due to the up-regulations of histone H3 and HSP70. PMID- 26814074 TI - [Effect of PON1 overexpression on mouse diaphragmatic muscle cells injury caused by acute dichlorvos poisoning]. AB - OBJECTIVE: To investigate the effect of paraoxonase1 (PON1) overexpression on mouse diaphragmatic muscle cells injury caused by acute dichlorvos poisoning. METHODS: Mouse diaphragmatic muscle cells were cultured routinely and infected with overexpression lentivirus. Cells were divided into normal control group, DDVP group, LV-GFP + DDVP group, LV-PON1 + DDVP group. Cell viability was determined by CCK-8 assay. Flow cytometry was used to detect cell apoptosis. The mRNA and protein expression of PON1 and Nrf2 in mouse diaphragmatic muscle cells was measured by RT-PCR and Western blot. Enzyme-linked immunosorbent assay was used to determine levels of acetyl cholinesterase (AchE), heme oxygenase 1 (HO-1) and quinone oxidoreductase-1 (NQO-1) in mouse diaphragmatic muscle cells. The activity of superoxide dismutase (SOD) and catalase (CAT) as well as malondialdehyde (MDA) content in cells was measured by chemical colorimetry. RESULTS: After induced by 0, 80, 160, 320, 640 umol/L DDVP for 24 hours, the viability of mouse diaphragmatic muscle cells was (100 +/- 3.82)%, (82.13 +/- 2.60)%, (53.57 +/- 5.05)%, (30.77 +/- 3.30)%, (14.20 +/- 2.19)% respectively, changing in a concentration-dependent manner (P < 0.05). After induced by 160 umol/L DDVP for 0, 6, 12, 24 hours, the viability of mouse diaphragmatic muscle cells was (100.17 +/- 2.74)%, (76.13 +/- 6.01)%, (66.53 +/- 3.55)%, (53.57 +/- 5.05)%, changing in a time-dependent manner (P < 0.05). The PON1 protein level in LV-PON1 group was higher than that of blank control group (0.370 +/- 0.015 vs 0.232 +/- 0.004, 0.197 +/- 0.015 vs 0.037 +/- 0.003, P < 0.05). The cell viability of LV-PON1 group is higher than that of DDVP group at different time point after induction of DDVP (P < 0.05). After induced by DDVP for 24 hours, the cell apoptosis rate and MDA content in LV-PON1 group were lower than those of DDVP group (P < 0.05). While levels of AchE, PON1 and Nrf2 protein expression, SOD and CAT, HO-1 and NQO-1 were higher than those of DDVP group (P < 0.05). CONCLUSIONS: The overexpression of PON1 could effectively alleviate AchE inhibition by DDVP and induce Nrf2 expression to exert antioxidant effect, thus protected the mouse diaphragmatic muscle cells. PMID- 26814075 TI - [Effect of IFN-alpha on hepatic cancer SMCC-7721 cell via PI3K/Akt signaling pathway and related mechanism research]. AB - OBJECTIVE: This study explored how interferon alpha (IFN-alpha) influenced liver cancer SMCC-7721 cell via PI3K/Akt signaling pathway. METHODS: The effect of IFN alpha on the viability of SMCC-7721 cell was measured by MTT assay. The effect of IFN-alpha on SMCC-7721 cell cycle was measured by flow cytometry. The activation of PI3K/Akt signaling pathway and downstream target genes expression level of glycogen synthase kinase 3 beta (GSK-3beta), and cell cycle protein (Cyclin D1), p21, C-myc, Survivin were assayed by Western blot. RESULTS: MTT assay indicated IFN-alpha (5, 10, 15 U/L) could inhibit SMCC-7721 cell viability, and the inhibitory rate was the highest at 48 h. IFN-alpha made SMCC-7721 cell arrested. Western blotting assays presented IFN-alpha could down-regulate expression of PI3K and suppress the phosphorylation of Akt, and then inhibit phosphorylation of GSK-3beta. It could also reduce the expression levels of Cyclin D1, C-myc and Survivin but increase the level of p21. CONCLUSION: These results suggested IFN alpha could depress the growth and proliferation of liver cancer SMCC-7721 cell via blocking PI3K/Akt signaling pathway, and the molecular proteins Cyclin D1, p21, C-myc, Survivin were involved. PMID- 26814076 TI - [Efficacy of sildenafil citrate in men with erectile dysfunction following bilateral nerve-sparing radical prostatectomy: systematic review and meta analysis]. AB - OBJECTIVE: To systematically assess the efficacy and safety of oral sildenafil citrate for post bilateral nerve-sparig radical prostatectomy (post-BNSRP) erectile dysfunction (ED). METHODS: The following keywords: sildenafil, radical prostatectomy were used to search in Medline, Pubmed, Web of Science, Cochrane Library, CNKI, WanFang Database. The title, abstract and keywords of each article were independently screened by two reviewers. Randomized controlled trials (RCT) published between 1990 and 2014 were retrieved according to our inclusion and exclusion criteria. The efficacy and safety of oral sildenafil citrate for post BNSRP ED were systematically assessed by meta-analysis. RESULTS: Four RCTs with 320 cases were included after literature retrieval and filtering. The potency rates were 32.1% (35/109) and 11.3% (7/62) between sildenafil and placebo groups after meta-analysis and showed statistically significant differences (OR = 4.66, 95% CI: 1.79-12.11). IIEF-5 score in sildenafil group was significant higher than that in the placebo group (WMD: 4.73, 95% CI: 3.26-6.19). In subgroup meta analysis, the potency rates in high-dose, low-dose sildenafil groups and placebo groups were 30.4% (14/46), 25.0% (10/40) and 4.5% (2/44), respectively. There were statistically significant differences between the high-dose subgroup and placebo group (OR = 9.32, 95% CI: 1.96-44.23), and the low-dose subgroup and placebo group (OR = 6.99, 95% CI: 1.43-34.22). But there was no significant difference between high-dose and low-dose subgroups (OR = 1.31, 95% CI: 0.51 3.40). CONCLUSIONS: Compared with placebo, sildenafil has considerable efficacy for erectile function rehabilitationas as a primary treatment for post-BNSRP ED. There is no significant difference between high-dose and low-dose schedule for its efficacy. However, further studies are required to optimize treatment. PMID- 26814078 TI - [Clinical significance of new urine red blood cell parameter in different kinds of glomerulonephritis]. AB - OBJECTIVE: To investigate the clinical value of new kinds of urinary erythrocyte morphology parameter in discriminating different pathology types of glomerulonephritis. METHODS: All of the 52 urine samples were from glomerulonephritis patients who had been diagnosed by renal biopsy results. The change of the percentage of acanthocytes, the size of RBC, the shape of RBC between the primary glomerulonephritis (39 cases) and secondary glomerulonephritis (13 cases) urine were detected by AVE-764 fully automatic urine cell analyzer. RESULTS: Acanthocytes could be found in both primary glomerulonephritis and secondary glomerulonephritis. Of the patients whose acanthocytes percentages above 10%, 94.1% had primary glomerulonephritis and 5.9% had secondary glomerulonephritis. The picture of size-shape phase were classified as strip-type, inverted triangle-type and hanging tail-type. 95.2% Strip-type cases were from primary glomerulonephritis patients. Triangle-typenormally cases were all from primary glomerulonephritis patients. Hanging tail-type cases were all from secondary glomerulonephritis. CONCLUSION: High acanthocytes percentage is most common in primary glomerulonephritis, going with the size and shape of RBC can be useful in the differential diagnosis of different pathology types of glomerulonephritis. PMID- 26814077 TI - [Efficacy and safety of active vitamin D3 supplement in maintenance hemodialysis patients: a meta-analysis]. AB - OBJECTIVE: To evaluate the efficacy and safety of active vitamin D3 treatment in maintenance hemodialysis patients (MHD). METHODS: We conducted a comprehensive search of the following databases: PubMed, Embase, Google scholar, CNKI, VIP, Wanfang data and CBM, to identify randomized controlled trials (RCTs) of active vitamin D3 supplementation in MHD patients up to November 2014. Meanwhile, we manually searched the reference lists of identified studies. The selection of studies, assessment of methodological quality and data extraction were performed independently by two researchers. Statistical analyses were performed using RevMan software, version 5.0. RESULTS: A total of 10 trials were included. There was a significant improvement in serum albumin (ALB) and an associated decline in PTH, alkaline phosphatase (ALP), C-reactive protein (CRP) and interleukin-6 (IL 6) in active vitamin D3-treated group (standardized mean difference (SMD) or weighted mean difference (95% CI): 0.47 (0.06, 0.88), -2.49 (-3.96, -1.02), 50.55 (-83.91, -17.19), -1.53 (-1.93, -1.12) and -4.71 (-7.48, -1.94), respectively). There was no statistical difference in the incidence of hyperphosphatemia, adverse events and mortality between the treatment and control group (RR (95% CI): 1.31 (0.96, 1.79), 0.85 (0.55, 1.32), 1.49 (0.80, 2.74), respectively). But there was a significant increase in serum calcium and calcium phosphorus product in treatment group (RR (95% CI): 2.10 (1.18, 3.75) and 3.65 (1.45, 9.17), respectively). CONCLUSIONS: Currently available evidence suggests that active vitamin D3 is effective in treating secondary hyperparathyroidism, renal osteodystrophy, and improving malnutrition and microinflammation in MHD patients, without obvious adverse events. However, the occurrence of calcium and phosphate abnormalities should be closely monitored. PMID- 26814079 TI - [Exploratory study of 3D printing technique in the treatment of basilar invagination and atlantoaxial dislocation]. AB - OBJECTIVE: To investigate the clinical application value of the 3D printing technique in the treatment of basilar invagination and atlantoaxial dislocation. METHODS: From January 2013 to September 2013, 10 patients with basilar invagination and atlantoaxial dislocation needing posterior fixation undertook 3D printing modes at the Department of Neurosurgery in PLA General Hospital. The 1:1 size models were established from skull base to C4 level with different colors between bone structures and vertebral arteries. The simulation of screw insertion was made to investigate the fixation plan and ideal entry point to avoid vertebral artery injury. After obtaining the individual screw insertion data in 3D printing modes, the according surgical operations were performed. The actual clinical results and virtual screw data in 3D printing mode were compared with each other. RESULTS: The 3D printing modes revealed that all the 10 patients had the dysplasia or occipitalized C1 posterior arch indicating C1 posterior arch screw implantation was not suitable. C1 lateral masses were chosen as the screws entry points. C2 screws were designed individually based on the 3D printing modes as follows: 3 patients with aberrant vertebral artery or narrow C2 pedicle less than 3.5 mm were not suitable for pedicle screw implantation. Among the 3 patients, 1 was fixed with C2 laminar screw, and 1 with C2-3 transarticular screw and 1 with C3 pedicle screw (also combined with congenital C2-3 vertebral fusion). Two patients with narrow C2 pedicle between 3.5 and 4mm were designed to choose pedicle screw fixation after 3D printing mode evaluation. One patient with C1 lateral mass vertically dislocated axis was planned with C1-2 transarticular screw fixation. All the other patients were planned with C2 pedicle screws. All the 10 patients had operation designed as the 3D printing modes schemes. The follow-up ranged from 12 to 18 months and all the patients recovered from the clinical symptoms and the bony fusion attained to 100%. CONCLUSIONS: 3D printing mode could provide thorough information of the bony structure abnormalities and route of vertebral artery. It is helpful for setting operation strategy and designing screw entry point and trajectory and avoiding vertebral artery and spinal cord injury and thus deserves generalization. PMID- 26814080 TI - [Evaluation of dysfunction of hand and clinical efficacy in patients with hirayama disease treated with surgery by Jebsen-Taylor Test]. AB - OBJECTIVE: To investigate the clinical efficacy of cervical anterior internal fixation and bone grafting fusion by comparative analyzing hand dysfunction in Hirayama disease patients using Jebsen-Taylor Test (JTT). METHODS: From Feb 2010 to Jan 2014, 20 hirayama disease patients who underwent surgery were enrolled in Department of Orthopaedics, Peking University Third Hospital. JTT were evaluated for the 20 patients before and after surgery. Among them, 9 patients were evaluated before and at three months, one year and more than 2 years after surgery. RESULTS: All sections of the JTT scale indicated that the patients with CSM exhibited a significant impairment compared with healthy adults. Each scale of JTT was improved after surgery in addition to picking up small objects and placing them in a can and simulated feeding. The whole time were improved from 72.3 s to 60.2 s. CONCLUSION: JJT is a valid efficacy evaluation in assessing the impairment of hand and upper extremities of patients with Hirayama disease and the surgery can improve patients' hand function. PMID- 26814081 TI - [Radiological factors influencing pulmonary function test in severe spinal deformity]. AB - OBJECTIVE: To investigate the pulmonary dysfunction patterns in severe spinal deformity and to identify radiological factors affecting the pulmonary function. METHODS: From September 2009 to December 2014, a total of 66 patients were involved in this Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University. Preoperative pulmonary function testing (PFTs) and radiographic examination were performed on all of the involved patients. Correlation analysis and subsequent stepwise multiple regression analysis were carried out to assess the associations between radiographic measurements of deformity and the results of pulmonary function testing. RESULTS: Fifty-seven out of 66 patients had impaired pulmonary dysfunction, and more than half of were <=59% predicted forced expiratory volume in 1 second (FEV1). Most of the patients with severe spinal deformity demonstrated a restrictive pattern of pulmonary function. The magnitude of the major curve, the number of involved thoracic vertebrae had significant effect on pulmonary function. While these 2 factors were associated with an increased risk of pulmonary impairment, they explained only 46.2%-55.1% of the observed variability in vital capacity, forced vital capacity, and forced expiratory volume in one second. CONCLUSIONS: Preoperative PFTs are clinically impaired in 86% of patients with severe spinal deformity, and more than half of that were moderate and severe pulmonary dysfunction. The magnitude of the major curve and the number of involved thoracic vertebrae are the main risk factors influencing the pulmonary dysfunction. PMID- 26814082 TI - [Correlation of region blood perfusion and glucose metabolism of the prefrontal lobes with clinical features in patients with first-episode depression]. AB - OBJECTIVE: To explore the cerebral blood flow (CBF) by three-dimensional arterial spin labeling (3D-ASL) and the standardized uptake value (SUV) of 18F fluorodeoxyglucose (18F-FDG) in the prefrontal lobe of patients with major depression disorder (MDD), and analyze their correlations with patients' depressive symptoms. METHODS: 3D-ASL and 18F-FDG positron emission tomography/computed tomography (PET/CT) were performed in 17 MDD patients and 16 healthy controls under the resting state. The depressive symptoms were classified into seven factors using Hamilton depression rating scale. Regional cerebral blood flow (CBF) and standardized uptake value (SUV) were compared between the patients and healthy controls using a two-sample t-test, and the correlation between the CBF and SUV with the patient Hamilton scores was examined using Spearman analysis. RESULTS: Decreased regional CBF values were present in the bilateral middle and the right superior frontal gyrus in patients, and decreased regional SUVs were observed in the bilateral superior, middle and inferior frontal gyrus. The significant correlation between the CBF and SUV values with the patients' Hamilton scores was mainly observed in the left middle, right middle and the right inferior frontal gyrus. CONCLUSION: 18F-FDG PET/CT is more sensitive than ASL in identifying the functional abnormalities in the prefrontal lobe. Decreased CBF and SUV in the prefrontal lobe closely correlate with the Hamilton Depression Rating Scale scores. We speculate that the left middle frontal gyrus may be a key responsible functional region in patients with MDD. PMID- 26814083 TI - [Clinical features and treatment of paraneoplastic neurological syndrome associated with small cell lung cancer]. AB - OBJECTIVE: The aim of this study is to explore the clinical characteristics, treatment and prognosis of pareneoplastic neurological syndrome (PNS) associated with small cell lung cancer (SCLC) in a single-center cohort. METHODS: We retrospectively and consecutively reviewed 34 patients (22 male and 12 female, mean age 55.4 years old) diagnosed as PNS associated with SCLC in our hospital from 2001 to 2014 and investigated the clinical features, related antibodies, treatment and prognosis in this cohort. RESULTS: In a total of 34 patients, 31 (91.4%) presented with neurological symptoms prior to the diagnosis of cancer. Lambert-Eaton syndrome (13/34, 38.2%) was the most common subtype, followed by paraneoplastic sensory neuronopathy (10/34, 29.4%), paraneoplastic cerebellar degeneration (7/34, 20.6%), limbic encephalitis (6/34, 17.6%) and brainstem encephalitis (1/34, 3%). Anti-neuronal antibodies were positive in 9 out of a total of 24 patients (37.5%) who performed the tests. There were 28 (82.4%) patients who received the treatment for the primary tumor. Of them, operation of removing the tumor was performed in 4 patients. 5 patients received treatment of suppression of the immune response to PNS. Significant neurological improvement was found in a patient who received operation combined with immunotherapy after a 3-year follow-up. CONCLUSIONS: The majority of patients with PNS are unknown to have cancer at the time of diagnosis. Early recognition of PNS is helpful to the treatment of the tumor. PNS has diverse presentations, affecting both the central and peripheral nervous system, which makes the diagnosis hard. Operation of removing the tumor and immune suppression may slow the immune response, creating the greatest chance for neurologic improvement or symptom stabilization. PMID- 26814084 TI - [Follow up study on auditory development of congenital hearing-impaired infants and toddlers]. AB - OBJECTIVE: To study the characteristics of auditory ability development in hearing-impaired infants and toddlers under home-based early intervention, and provide the theoretical basis for the development of rehabilitation and assessment strategies. METHODS: The clinical data was collected from subjects from 5 provinces between 2012 and 2014 in China. A total of 80 subjects were enrolled and divided into 2 groups with 1 year interval according to chronological age. Initials, finals and disyllable words in Auditory Ability Test were used to assess the auditory development before intervention (0 month) and after intervention (6, 12, 18, 24 months). Data was analyzed by repeated measures analysis of variance. RESULTS: In 1 age group and 2 age group, the main effect of recovery time and chronological age were significantly different in initials, finals and disyllable (P<0.05). The recognition ability of initials, finals and disyllable words in 1 age group were less than 2 age group at 6- and 12-month after early intervention (P<0.05). After 2 years hearing intervention and rehabilitation, the recognition rates of initials, finals and disyllable words were 88%+/-11%, 90%+/-11% and 92%+/-9%, respectively. 18%, 30% and 47%, respectively, hearing-impaired children achieved full score in initials, finals and disyllable words. 70% hearing-impaired children reached more than 90% recognition ability in initials, finals and disyllable words. CONCLUSIONS: The chronological age and recovery time are principle factors for auditory development in hearing-impaired children; 70% hearing-impaired children have reached grade A after 2 years hearing intervention and rehabilitation, and performed well in hearing identification and speech intelligibility. PMID- 26814085 TI - [Narrow band imaging-assisted holmium laser resection reduced the recurrence rate of non-muscle invasive bladder cancer: a prospective, randomized controlled study]. AB - OBJECTIVE: To compare the differential effects of narrow band imaging (NBI) assisted holmium laser with transurethral resection on the 1-year recurrence rate of non-muscle invasive bladder cancer (NMIBC), and to evaluate the clinical values of NBI-assisted holmium laser resection for NMIBC (NBI-HoLRBt). METHODS: During the period of February 2013 to February 2014, 178 cases of NMIBC were randomly divided into NBI-HoLRBt group and white light imaging (WLI) assisted transurethral resection of bladder tumor (WLI-TURBt) group. In NBI-HoLRBt, all suspicious lesion identified by either WLI or NBI were resected with WLI and in NBI mode for lesion only visible with NBI. At the end of the procedure, a NBI cystoscopic examination was performed to assess the margins of the resection areas and to identify eventual residual lesions. In WLI-TURBt group, only WLI and TURBt were applied. All patients underwent routine follow-up with WLI and NBI cystoscopy supplemented with cytology every 3 month. The recurrence risk of patients with NMIBC subjected to either NBI-HoLRBt or WLI-TURBt was compared at 3 and 12 month. RESULTS: The 3-month and 1-year recurrence rate was 18.48% (17/92) and 38.04% (35/92) respectively in the WLI-TURBt group, it was 5.81% (5/86) and 18.60% (16/86) in the NBI-HoLRBt group (both P<0.05). In addition, the in situ recurrence rate was less in the NBI-HoLRBt than WLI-TURBt group (2.33% vs 14.13%, P<0.05). CONCLUSION: NBI-assisted holmium laser resection of bladder tumor can reduce the 3-month and 1-year recurrence risk of NMIBC and should be considered a valuable clinical therapeutic method for NMIBC. PMID- 26814086 TI - [Clinical values of hemodynamics assessment by parametric color coding of digital subtraction angiography before and after endovascular therapy for critical limb ischaemia]. AB - OBJECTIVE: To investigate the feasibility of parametric color coding of digital subtraction angiography (Syngo iFlow) for hemodynamics assessment in patients with critical limb ischemia in pre- and post-endovascular therapy. To explore the correlation between Syngo iFlow and the conventional techniques. METHODS: from January 2013 to December 2014, Clinical data of 21 patients with TASC II type B and type C femoropopliteal arteriosclerotic occlusive disease who were treated by percutaneous transluminal angioplasty and/or primary stent implantation in Nanjing first hospital were analyzed retrospectively. Of these patients there were 10 males and 11 females with an average age of (72+/-6) years (range from 58 85 years). The treatment efficacy was assessed by the variation of a series of clinical symptoms indexes (such as pain score, cold sensation score and intermittent claudication score), ankle braehial index (ABI) and transcutaneous oxygen pressure (TcPO2). Angiography was performed with the same protocol before and after treatment and parametric color coding of digital subtraction angiography was created by Syngo iFlow software on a dedicated workstation. The time to peak (TTP) of artery and tissue perfusion selected at the same regions of foot and ankle were measured and analyzed to evaluate the improvement of microcirculation and hemodynamics of the ischemic limb. The correlations between Syngo iFlow and the traditional clinical evaluation methods were explored using the Spearman rank correlation test. RESULTS: All patients (21 limbs) underwent successful endovaseular therapy. The mean pain score, cold sensation score, intermittent claudication score, ABI and TcPO2 before treatment were (0.48+/ 0.68), (2.71+/-0.72), (2.86+/-0.85), ABI (0.33+/-0.07), TcPO2 (26.83+/-3.41) mmHg. While 1 week after treatment all above indicators were (2.57+/-0.93), (0.33+/-0.48), (0.90+/-0.54), (0.69+/-0.11), TcPO2 (53.75+/-3.60) mmHg respectively. There were significant statistical differences between pre- and post-treatment (P<0.05). The pre- and post-operative TTP of artery and tissue perfusion were (14.07+/-1.77) vs (10.43+/-2.05) s, (18.75+/-2.72) vs (15.38+/ 2.78) s. For assessment of hemodynamic changes during and after treatment, parametric color coding of digital subtraction angiography (Syngo iFlow) was assumed to show the limb blood flow and perfusion were improved and the differences were statistically significant. The Spearman rank correlation test showed the TTP of artery was positively correlated with ABI, TcPO2 (r=0.65, 0.73, P<0.05), the TTP of tissue perfusion was also positively correlated with ABI, TcPO2 (r=0.60, 0.60, P<0.05). CONCLUSION: Parametric color coding of digital subtraction angiography (Syngo iFlow) is a real-time, sensitive and quantitative tool that might provide additional support in the hemodynamics evaluation of endovascular treatment for patients with lower extremity peripheral arterial occlusion disease. PMID- 26814087 TI - [The best noise index combined with ASIR weighting selection in low-dose chest scanning]. AB - OBJECTIVE: To discuss the best noise index combined with ASIR weighting selection in low-dose chest scanning based on BMI. METHODS: 200 patients collected from May to December 2014 underwent non-contrast chest CT examinations, they were randomly assigned into standard dose group (Group A, NI15 combined with 30% ASIR) and low dose groups (Group B, NI25 combined with 40% ASIR, Group C, NI30 combined with 50% ASIR, Group D, NI35 combined with 60% ASIR), 50 cases in each group; the patients were assigned into three groups based on BMI (kg/m2): BMI<18.5; 18.5<=BMI<=25; BMI>25. Signal-to-nosie ratio (SNR), contrast-to noise ratio (CNR), CT dose index volume (CTDIvol), dose-length product (DLP), effective dose (ED) and subjective scoring between the standard and low-dose groups were compared and analyzed statistically. Differences of SNR, CNR, CTDIvol, DLP and ED among groups were determined with ANOVA analysis and the consistency of diagnosis with Kappa test. RESULTS: SNR, CTDIvol, DLP and ED reduced with the increase of nosie index, the differences among the groups were statistically significant (P<0.05). Kappa value of the two reviewers were 0.888. Subjective scoring of four groups were all above 3 points in BMI<18.5 kg/m2 group; subjective scoring of ABC groups were all above 3 points in 18.5 kg/m2<=BMI<=25 kg/m2 group and subjective scoring of AB groups were all above 3 points in BMI>25 kg/m2 group. CONCLUSIONS: NI35 combined with 60% ASIR in BMI<18.5 kg/m2 group; NI30 combined with 50% ASIR in 18.5 kg/m2<=BMI<=25 kg/m2 group; NI25 combined with 40% ASIR in 18.5 kg/m2<=BMI<=25 kg/m2 group were the best parameters combination which both can significantly reduce the radiation dose and ensure the image quality. PMID- 26814088 TI - [Feasibility of treatment of cesarean scar pregnancy with dilatation and curettage under ultrasound guidance]. AB - OBJECTIVE: The present study sought to investigate the predictors of successful dilatation and curettage (D&C) in treatment of cesarean scar pregnancy (CSP). METHODS: Retrospective analysis was conducted in 84 CSP patients undergoing D&C from January 2013 to December 2014. Failure was defined as D&C followed by transcatheter uterine arterial embolization due to uncontrolled hemorrhage. Sub stratification of success group as residue group or non-residue group was performed according to the residues at the site of cesarean scar after D&C. The univariate logistic regression and linear regression were used to assess the predictors of the failure and residues. ROC curve was used to assess the cut-off values of the predictors. RESULTS: D&C under ultrasound guidance succeeded in 75 patients (89.3%) and 36 patients had residues at the site of cesarean scar among them (48%), 9 patients failed in D&C (10.7%). High Serum human chorionic gonadotropin (hCG), small gestation sac (GS), thin cesarean scar myometrium thickness (CSM) and low peritrophoblastic flow resistance index (RI) were risk factors of D&C failure in treatment of CSP. That serum hCG>97 006 U/L was prime predictor of failure (predictive value 100%, 95% CI 94.9%-100%). High success ratio was observed in patients with serum hCG<58 076 U/L, GS<=19 mm, CSM>2.7 mm, and RI>0.25. And days of menopause<=41 d, GS<=15 mm, CSM>3.7 mm, RI>0.4 and serum hCG<3 935 U/L were predictors of complete success of D&C. The postponed restoration of menstruation was observed in patients with residues, which did not induce amenorrhea and disappeared in 1-3 months after procedures. CONCLUSION: Early diagnosis and treatment is associated with successful D&C in treatment of CSP. HCG, GS, CSM and RI are valuable in predicting the prognosis of D&C in treatment of CSP. PMID- 26814089 TI - [Expression of Daxx and HPV16 E6 and its significance in cervical lesions]. AB - OBJECTIVE: To investigate the expression of death domain associated protein (Daxx) and human papillomavirus 16 E6 protein (HPV16 E6) in cervical lesions and analyze their significance. METHODS: Immunohistochemical SABC method was used to detect the expression of Daxx and HPV16 E6 in 194 cases of cervical tissues with different lesions. RESULTS: (1) The positive expression rate of Daxx was 28.57% (12/42), 40.00% (18/45), 65.91% (29/44), 66.67% (42/63), respectively, in chronic cervicitis, cervical intraepithelial neoplasia I-II (CIN I-II), CIN III and cervical squamous cell carcinoma. The positive expression rate of HPV16 E6 was 15.38% (6/39), 36.17% (17/47), 46.30% (25/54), 100.00% (24/24) in the above four groups. The positive rates in cervical cancer group and high grade CIN group were significantly higher than these in low level of CIN group and chronic cervicitis group (P<0.05). (2) The expression of Daxx was stronger in HPV16 E6 high positive group than that in HPV16 E6 low positive group (P<0.05). (3) There was no significant relationship between the expression of Daxx and pathological classification, clinical stage, situation of lymph node metastasis or patients' age in cervical squamous cell carcinoma (P>0.05). (4) There was significant positive relationship between Daxx and HPV16 E6 expression (r=0.695, P<0.05). CONCLUSIONS: The expression of Daxx and HPV16 E6 gradually increases with cervical lesion degree aggravating. Here might be synergy between them, and both could promote the development of cervical lesions. PMID- 26814090 TI - [Diagnostic value of Kimura's disease with ultrasonography]. AB - OBJECTIVE: To explore the diagnostic value of ultrasonography for Kimura's disease (KD). METHODS: Retrospectively analyzed the results of two dimension and color Doppler of 21 Kimura's disease carried by 19 patients who were resected and confirmed by pathologhy. RESULTS: Twenty-one KD cases were detected by the ultrasound while none of them was diagnosed by ultrasonography. 21 cases were showed in the lymph nodes (42.9%, 9/21), parotid gland (4.8%, 1/21) and soft tissues (52.4%, 11/21). The masses both in the lymph and in the parotid gland marked hypoechogenicity and round or like-round. Cases in the soft tissues marked hypoechogencity or hyperechogenicity. Color Doppler flow pattern II to III were showed in 19 cases (90.5%, 19/21). CONCLUSION: Ultrasonography enables a confident preoperative diagnosis of Kimura's disease. PMID- 26814091 TI - [The effect of Ixabepilone on NSCLC cells radio-sensitivity under quiescent or hypoxic condition]. AB - OBJECTIVE: To evaluate the effect of Ixabepilone on quiescent or hypoxic cells response to ionizing radiation. METHODS: NCI-H460 and A549, two human NSCLC cell lines, were employed in this experiment. Quiescent cells (QC) or hypoxic cells (HC) were induced as mentioned previously and untreated cells as control. A colony forming assay was applied to compare cellular radio-sensitivity with or without Ixabepilone. Flow cytometry and Western blot analysis were used to detect cell cycle distribution and apoptosis. RESULTS: Along with an increased population of G1 cell (NCI-H46 P=0.001 3; A549 P=0.006), both HC and QC were exhibited radio-resistance compared to untreated cells (survival fraction: NCI H460 P=0.003; A549 P=0.000 1). Moreover, it was found that Ixabepilone, which induced apoptosis in both IR-treated or untreated NSCLC cells, significantly enhanced cells death under hypoxia (decrease of survival fraction: NCI-H460 P=0.000 2; A549 P<0.01). CONCLUSION: The existence of quiescent or hypoxic cells in solid tumors poses a critical therapeutic problem since they were resistant to IR. Ixabepilone, which induces apoptosis in NSCLC, showed great radio sensitization effect on hypoxic cells. Following work will focus on whether Ixabepilone could increase hypoxic tumor cells radio-sensitivity in vivo, which could provide useful data for the application of Ixabepilone in clinical practice. PMID- 26814092 TI - [Histocompatibility of nano-hydroxyapatite/poly-co-glycolic acid tissue engineering bone modified by mesenchymal stem cells with vascular endothelial frowth factor]. AB - OBJECTIVE: To explorec Histocompatibility of nano-hydroxyapatite/poly-co-glycolic acid tissue engineering bone modified by mesenchymal stem cells with vascular endothelial frowth factor transinfected. METHODS: Rat bone marrow mesenchymal stem cells (BMSCs) was separated, using BMSCs as target cells, and then vascular endothelial growth factor (VEGF) gene was transfected. Composite bone marrow mesenchymal stem cells and cells transfected with nano-hydroxyapatite (HA)/polylactic-co-glycolic acid (PLGA). The composition of cell and scaffold was observed. RESULTS: The blank plasmid transfection was 39.1%, 40.1% in VEGF group. The cell adhesion and growth was found on the scaffold pore wall after 5 days, and the number of adherent cells in the nano-HA/PLGA composite scaffold material basically had no significant difference in both. CONCLUSION: Although the nano HA/PLGA scaffold material is still not fully meet the requirements of the matrix material for bone tissue engineering, but good biocompatibility, structure is its rich microporous satisfaction in material mechanics, toughening, enhanced obviously. Composition scaffold with BMSCs transfected by VEGF plasmid, the ability of angiogenesis is promoted. PMID- 26814094 TI - [Surgical treatment for hepatocellular carcinoma beyond the Barcelona clinic liver cancer staging system]. PMID- 26814093 TI - [Next-generation sequencing targeting targeted therapies in clinical oncology:challenges and thoughts]. PMID- 26814095 TI - [Diagnosis, evaluation and individualized treatment of severe asthma]. PMID- 26814096 TI - [Environmental factor control and asthma]. PMID- 26814097 TI - [Impact of chronic rhinitis and rhinosinusitis on the asthma control]. PMID- 26814098 TI - [Difficult-to-asthma and obstructive sleep apnea]. PMID- 26814099 TI - [Concerning the personalized medicine for asthma: from phenotype to endotype]. PMID- 26814100 TI - [Comparison of clinicopathological characteristics and prognosis of intrahepatic biliary cystic tumor between male and female patients]. AB - OBJECTIVE: To describe the clinicopathological characteristics and prognosis of intrahepatic biliary cystic tumor (IBCT) and compare the difference betwwen male and female patients. METHODS: 11 male and 45 female patients with histological confirmed IBCT from January 2003 to April 2014 were envolved. clinical characteristics, laboratory examination, radiological features, treatment method and prognosis were analyzed. RESULTS: The mean age of male patients with IBCT was significantly older than that of female patients (54.9+/-10.1 years vs 46.2+/ 12.9 years, P=0.041). There were no significant differences in radiological features between male and female patients except for mural nodules (10/11 vs 15/45, P=0.001). Intrahepatic biliary cystadenocarcinoma (IBC) was more common in male patients than female patients (8/11 vs 16/45, P=0.041). Male patients had worse prognosis than female patients (P=0.014). 1-year, 3-year, and 5-year survival of male patients was 90.9%,45.5%,30.3%, respectively. However, 1-year, 3 year, and 5-year survival of female patients was 94.8%,82.7%,78.6%. CONCLUSIONS: Male patients had low incidence of IBCT, and were more common for IBC. Even with complete resection, the long-term survival was still poor, close follow-up were recommended especially for male patients. PMID- 26814101 TI - [Hepatic resection for hepatocellular carcinoma involving a single large tumor, multiple tumors or macrovascular invasion]. AB - OBJECTIVE: To investigate the safety and efficacy of hepatic resection for those patients with large/multinodular hepatocellular carcinoma (HCC) or those involving macrovascular invasion (MVI). METHODS: PubMed was systematically searched for studies examining the safety and efficacy of hepatic resection for treatment of HCC involving a single large tumor (>5 cm) or multiple tumors (>2), or those involving MVI. RESULTS: The identified 52 studies involving 14 922 patients that investigated the use of hepatic resection for large/multinodular HCC, and 25 studies with 4 412 patients that investigated hepatic resection for HCC with MVI. Median in-hospital mortality of patients with either type of HCC was significantly lower in Asian studies (2.7%) than in non-Asian studies (7.3%, P<0.001). Median overall survival rate was significantly higher for all Asian patients with large/multinodular HCC than for all non-Asian patients both at the time of 1 year (81% vs 65%, P<0.001) and 5 years (42% vs 32%, P<0.001). However, median overall survival rate was similar for Asian and non-Asian patients with HCC involving MVI at the time of 1 year (50% vs 52%, P=0.46) and 5 years (18% vs 15%, P=0.95). There was an increasing trend in 5-year overall survival in patients with either type of HCC. CONCLUSIONS: Hepatic resection is reasonably safe and effective for the treatment of large/multinodular HCC and HCC with MVI. The available evidence argues for expanding the indications for hepatic resection in official treatment guidelines. PMID- 26814102 TI - [Protective effect of magnesium isoglycyrrhizinate combinated with verapamil on liver ischemia-reperfusion injury after semi-hepatectomy in rats]. AB - OBJECTIVE: To investigate protective effect of isoglycyrrhizinate combinated with verapamil on liver ischemia-reperfusion injury after semi-hepatectomy in rats. METHODS: Male SD rats were randomly divided into five groups: false operation (group A); rats subjected to 50%hepatectomy and 45 min of hepatic ischemia (group B); rats subjected to 50% hepatectomy and 45 min of hepatic ischemia, and treated with isoglycyrrhizinate (group C); rats subjected to 50% hepatectomy and 45 min of hepatic ischemia, and treated with verapamil (group D); rats subjected to 50% hepatectomy and 45 min of hepatic ischemia, and treated with isoglycyrrhizinate and verapamil (group E). Liver function, as well as morphology, SOD activity, FasL, caspase 3, and beta-catenin expression of rats were analyzed. RESULTS: Compared to group B, the levels of serum ALT of group E were significantly lower (P<0.05), SOD activity of liver tissue (98.8+/-7.1) were significantly higher (P<0.01), pathological changes were milder, FasL gene (1.327+/-0.193) and protein (0.010 9+/-0.001 4) expression were significantly lower (P<0.01). Caspase 3 protein expression levels (0.141 0+/-0.005 3) were significantly lower (P<0.001), beta-catenin protein expression levels (0.079 1+/-0.008 2) were higher significantly (P<0.01). CONCLUSIONS: Isoglycyrrhizinate combinated with verapamil can effectively reduce rats liver ischemia-reperfusion injury. The protective effect on liver cells may be mediated by inhibiting apoptosis caused by Fas/FasL system, increasing beta-catenin protein expression, promoting liver regeneration and relieving liver peroxidation damage. PMID- 26814103 TI - [Analysis on BK virus associated nephropathy related risk factors in renal transplant recipients]. AB - OBJECTIVE: To analyze the risk factors affecting BK virus associated nephropathy (BKVAN) after kidney transplantation. METHODS: Three screening methods for BKVAN including quantitative PCR assay for BK virus (BKV) DNA load in urine and plasma and quantitative assay of urine cytology concurrently with renal transplant biopsies for the evaluation of 615 patients from January 2006 to December 2014 were used. The renal allograft biopsy specimens were analyzed by routine histologic examination, immunohistochemistry and classified into three categories of BKVAN. Potential variables were analyzed by Logistic regression model multivariate analysis to assess and rank BKVAN related risk factors. RESULTS: The positive rate of urine decoy cell , BKV viruria and viremia in 615 renal recipients were 13.7% (84/615), 29.3% (180/615), and 8.8% (54/615), respectively. BKVAN were diagnosed in 49 recipients. The incidence and the median level of the number of the decoy cell, BK viral load in urine and plasma were higher in the BKVAN group than those in non-BKVAN group (all P<0.05). Tacrolimus (Tac) combined with mycophenolic acid (MPA) protocol (OR=12.4, P=0.001) and severe pneumonia post-transplant (OR=3.7, P=0.001) were the independent risk factors impacting on BKVAN in renal recipients. CONCLUSIONS: The renal recipients with high level of BKV replication, whose immunosuppressant protocol include Tac and MPA, should be suspected the diagnosis of BKVAN. PMID- 26814104 TI - [Different doses of dexmedetomidine for quiet extubation during anesthesia recovery in hypertensive patients]. AB - OBJECTIVE: To explore the feasibility of different doses of dexmedetomidine for quiet extubation during anesthesia recovery in hypertensive patients monitored with Narcotrend. METHODS: A total of 120 hypertensive patients scheduled for thyroid surgery from August 2012 to June 2014 in the Second Affiliated Hospital of Wenzhou Medical University, were randomly divided into 6 groups (n=20 each). Dexmedetomidine 0.4 (group M1), 0.6 (group M2), 0.8 (group M3) or 1.0 (group M4) ug.kg(-1).h(-1), remifentanil 0.1 ug.kg(-1).min(-1) (group R) and normal saline (group S) were infused for half an hour before the end of surgery, and extubation was carried out when Narcotrend index (NI) values were >=80 in each group. Data of heart rate (HR), systolic blood pressure (SBP) and minimal alveolar concentration (MAC) of sevoflurane were observed and recorded at the time of baseline (T0), half an hour (T1) and 15 min (T2) before the end of surgery, stopping sevoflurane (T3), before extubation (T4), 1 min (T5), 5 min (T6) and 10 min (T7) after extubation. Extubation time, recovery time and related adverse reactions were also recorded. RESULTS: Compared with T0, SBP and HR at T4 to T7 in four M groups were significantly lower (all P<0.05). SBP and HR at T6, T7 in group R were significantly lower than at T0 (all P<0.05). SBP at T6, T7 and HR at T4 to T7 in group R were significantly lower than that of group S (all P<0.05). SBP and HR at T4 to T7 in four M groups were significantly lower than that of group S and group R (all P<0.05). The values of MAC of sevoflurane at T2 and T3 in group R and M2-4 were significantly lower than at T1 and that of group S (all P<0.05). Recovery time in group M3 [(19.1+/-2.8) min] and group M4 [(20.6+/-4.1) min] were significantly longer compared with other four groups (all P<0.05). The percentage of cough grade at level I and II in each M group and group R during extubation was significantly higher than that in group S (85%, 85%, 90%, 95%, 80% vs 45%, all P<0.05). CONCLUSIONS: Dexmedetomidine could be safely used in hypertensive patients monitored with Narcotrend for quiet extubation during anesthesia recovery, but larger doses of dexmedetomidine may prolong the recovery time. PMID- 26814105 TI - [Risk factors for coronary artery calcification in patients with end-stage renal disease]. AB - OBJECTIVE: To explore risk factors for coronary artery calcification (CAC) inpatients with end-stage renal disease (ESRD). METHODS: A total of 53 ESRD patients undergoing regular hemodialysis (3 times a week) from August 2014 to March 2015 in the Fourth Hospital of Hebei Medical University were enrolled in the study. The patients were divided into the negative control group (13 cases) and three positive groups (11 mild calcification cases, 12 moderate calcification cases and 17 severe calcification cases) based on coronary artery calcification score (CACs). Clinical data of all patients at study entry were collected. Arterial blood samples were also collected at the start of the first hemodialysis (HD) session of the week to measure the levels of serum albumin, uric acid, calcium (Ca), phosphorus (P), magnesium, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), C reactive protein (CRP), beta-2 microglobulin (beta2-MG), free parathyroid hormone (iPTH), alkaline phosphatase, fibrinogen, hemoglobin (HGB) and ferritin. Meanwhile, levels of blood pH were detected after collecting pre- and post-HD blood samples to calculate DeltapH (post-HD pH subtracted pre-HD pH). Logistic regression analysis was performed to analyze the correlation of CACs with clinical data and previously-reported blood biochemical indicators, followed by analysis of the incidence of CAC and influential factors in ESRD patients. RESULTS: Severity of CAC was positively correlated with age (r=0.269), HD duration (r=0.341), serum calcium (r=0.358), serum phosphorus (r=0.186) and pre-HD pH (r=0.275), but negatively correlated with serum albumin (r=-0.192) and DeltapH (r=-0.302), all P<0.05. Logistic regression analysis revealed that age, HD duration, serum phosphorus level and DeltapH were independent risk factors for CAC in ESRD patients (P<0.05). In CAC positive groups, CAC was predominantly involved in the left anterior descending artery (P<0.05, P<0.01 and P<0.01 in mild, moderate and severe calcification group, respectively). CONCLUSIONS: CAC in ESRD patients seems to be affected by multiple factors, such as age, HD duration, serum phosphorus level and DeltapH. Moreover, DeltapH affects CAC mainly by pre-HD pH. Furthermore, left anterior descending artery is predominantly affected by CAC in ESRD patients. PMID- 26814107 TI - [Mechanisms of antimicrobial peptide cathelicidin secreted by non-tumorous cells for lung tumor growth]. AB - OBJECTIVE: To investigate the effect of antimicrobial peptide cathelicidin secreted by non-tumorous cells in lung tumor growth. METHODS: CRAMP(-/-) mice and WT mice were used to establish a lung cancer model via tail vein injection of Lewis lung carcinoma cells (LLC1). Lung was weighted and tumor number on the lung surface was counted. Kaplan-Meier (K-M) survival curve was used to analyze survival rate of mice. Expression of cathelicidin, Ki-67 and CD68 in the tumor tissue was measured by immunohistochemical analysis. BALF cells were stained with Diff Quik and percentages of leukocyte types were determined by light microscopy. RESULTS: Cathelicidin was high expression in inflammatory cells of tumor tissue, whereas weak expression in tumor cells. The lung weight and number of tumor in CRAMP-/- mice were (0.25+/-0.04)g and (9.60+/- 2.25), respectively, which were significantly lower than those of WT mice (0.65+/-0.05) g and (23.40+/- 2.68). The difference was statistically significant (t=6.07, 3.95, all P<0.05). And Kaplan-Meier survival analysis showed median survival time of CRAMP-/- mice was 49(46-51)d, which was longer than 34(28-39) d of WT mice (chi2=12.00, P<0.05). And the positive rate of Ki-67 tumor cells was significant reduced from (35.80+/ 2.96)% in WT mice to (18.80+/-2.38)% in CRAMP-/- groups (t=4.48, P<0.05). The total cell number as well as the number of lymphocytes, neutrophils, and macrophages in BALFs of CRAMP-/- mice were (4.72+/-0.86)*10(4), (0.08+/ 0.02)*10(4), (0.05+/-0.02)*10(4) and (4.60+/-0.84)*10(4), respectively, while of WT mice were (16.18+/-1.61)*10(4), (0.32+/-0.05)*10(4), (0.20+/-0.05)*10(4) and (15.66+/-1.57)*10(4). All of them had significant difference (t=6.28, 4.39, 3.00, 6.20, all P<0.05). In addition, the infiltration of macrophages into lung tumors was decreased in CRAMP-/- mice compared to WT mice, from (15.53+/-2.28)/high power field to (6.77+/-3.12)/high power field (t=3.41, P<0.05). CONCLUSIONS: Non tumor cells secreted cathelicidin promotes tumor cell proliferation and lung tumor growth. Recruitment of inflammatory cells such as macrophages into the tumor microenvironment may be the main mechanism of action. PMID- 26814106 TI - [Analgesic effect and safety of intercostal nerve cryoanalgesia after the video assisted thoracoscopic surgery]. AB - OBJECTIVE: To investigate the analgesic efficacy and safety of intercostal nerve cryoanalgesia after video-assisted thoracoscopic surgery (VATS). METHODS: This was a prospective randomized controlled study. From May 2014 to April 2015, 80 patients who would undergoing selective surgery performed by the same surgeon team were chosen, and were randomly divided into cryoanalgesia group and intravenous analgesia group by a random number table. Visual analogue scale (VAS) at resting and movement were measured on postoperative 4 h, 1 d, 2 d, 3 d, and the amount of supplemental morphine use and adverse reactions were recorded; plasma concentration of cortisol, blood glucose, C-reactive protein (CRP) and interleukin-6 (IL-6) were detected on preoperative and postoperative 4 h,1 d,2 d. RESULTS: Seventy-one patients with complete test process were included in the statistical analysis, including cryoanalgesia group (35 cases) and intravenous group (36 cases). No statistical differences were found in terms of age, gender, body mass index (BMI) between the two groups. VAS scores of cryoanalgesia group at movement on postoperative 4 h, 1 d, 2 d, 3 d were 5(5,7), 4(3,6), 3(3,4), 3(0,3), and in intravenous group were 5(5,6), 5(3,5), 3(3,4), 2(0,3), respectively, but there was no statistically different between two groups (P>0.05). Resting VAS scores of cryoanalgesia group on postoperative 4 h, 1 d, 2 d, 3 d were 3(2,4), 0(0,3), 0(0,0), 0(0,0), and in intravenous group were 3(0.5,4), 2(0,3), 0(0,1.5), 0(0,0) respectively, but there was no statistically different between two groups (P>0.05). Resting analgesic effectiveness (VAS<=5) of cryoanalgesia group were 91.4%, and in intravenous group were 97.2%, respectively. Median of morphine dosage was equal between two groups on postoperative 4 h, 1 d, 2 d, cumulative amount of morphine of cryoanalgesia group was higher than intravenous group, but the difference between the two groups was not statistically significant. Incidence of nausea and vomiting for intravenous group was 36.1%, significantly higher than cryoanalgesia group (17.1%, chi(2)=4.148, P<0.05). The change of plasma concentration of cortisol, C-response protein (CRP), interleuken-6(IL-6) was noticeable, but there was no statistical significance in each time point. CONCLUSION: The analgesic effect of both Intercostal nerve cryoanalgesia and intravenous analgesia after VATS is almost the same.Compare with intravenous analgesia, incidence of the adverse reactions of cryoanalgesia is lower, and there is no increasing in the stress response. PMID- 26814108 TI - [mRNA-binding protein Human-antigen R regulates alpha-SMA expression in human bronchia smooth muscle cells]. AB - OBJECTIVE: To investigate the role of mRNA binding protein Human-antigen R (HuR) in the over-expression of alpha-Smooth muscle actin (alpha-SMA) stimulated by Platelet-derived Growth Factor (PDGF) in cultured human bronchia smooth muscle cells. METHODS: Human bronchia smooth muscle cells cultured in vitro were divided into 0, 6, 12 and 24 h groups according to the time of PDGF treatment. Total HuR protein and total alpha-SMA protein expression were detected by Western blot. Total HuR mRNA and total alpha-SMA mRNA level were determined by quantitative real time-polymerase chain reaction. RNA interference technology was used to down regulate HuR protein level to study the protective effect of HuR in PDGF stimulated alpha-SMA protein expression. RESULTS: PDGF up-regulated the expression of HuR in a time-dependent manner. The relative expression levels of whole-cell HuR protein and mRNA in 0, 6, 12, 24 h groups were 0.23+/-0.09, 0.42+/ 0.11, 0.93+/-0.21, 1.37+/-0.28; 1.00+/-0.00, 1.09+/-0.03, 1.16+/-0.03, 1.27+/ 0.02 (all P<0.05). The relative expression levels of alpha-SMA protein and mRNA in 0, 6, 12, 24 h group also showed an increase trend marked in a time-dependent manner (1.03+/-0.08, 1.20+/-0.09, 1.39+/-0.11, 1.58+/-0.10; 1.00+/-0.00, 1.17+/ 0.02, 1.23+/-0.02, 1.45+/-0.03; all P<0.05). Using RNA interference technology to down-regulate HuR protein level, there was a decrease in alpha-SMA protein expression. CONCLUSION: PDGF stimulation can increase the expression of HuR and alpha-SMA in the smooth muscle cells, and HuR protein is involved in the expression of alpha-SMA protein stimulated by PDGF. PMID- 26814109 TI - [Can critically ill patients get benefit from fluid resuscitation with albumin?]. PMID- 26814110 TI - [Investigation on the predictive value of the dynamic changes of EVLWI and PVPI on the prognosis of ARDS patients]. AB - OBJECTIVE: To investigate the dynamic changes of extra vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) on the prognosis of acute respiratory distress syndrome (ARDS), and predict the risk factors affecting prognosis of ARDS. METHODS: 70 patients meeting ARDS Berlin definition, who were admitted to the ICU from July 2012 to July 2014, were analyzed with a prospective method. The patients were divided into a survival group and a death group according to their survival situation in 28 days. EVLWI (EVLWI1-EVLWI4), PVPI (PVPI1-PVPI4), DeltaEVLWI (subtracting EVLWI day 4 from day 1), and DeltaPVPI (subtracting PVPI day 4 from day 1) of the two groups of patients from the 1st day to the 4th day were monitored by the pulse indicator continuous cardiac output (PiCCO). Parameters including the acute physiology and chronic health evaluation (APACHE II) score, sequential organ failure assessment (SOFA) score, EVLWI, PVPI, DeltaEVLWI, DeltaPVPI, oxygenation index (OI), CVP, the number of organ dysfunction were compared between the two groups. Univariate analysis and multivariate logistic regression were used to analyze the independent risk factors associated with prognosis. Receiver operating characteristic curve (ROC curve) was drawn to evaluate the prediction performance of those risk factors in the prognosis of ARDS. RESULTS: Comparison of EVLWI and PVPI between the survival group and the death group of ARDS patients at different time points: EVLWI and PVPI showed no statistical difference from the 1st day to the 2nd day after admission, but those two parameters in the death group were higher than those in the survival group form the 3rd day to the 4th day after admission (P<0.01). The comparison of the dynamic changes of EVLWI and PVPI within the two groups: the EVLWI and PVPI in the survival group declined gradually from 1st day to 4th day after treatment, but that changing trend in the death group showed no statistical difference. DeltaEVLWI and DeltaPVPI changes in the survival group were higher than in the death group (P<0.01). They were independent risk factors of patients 28-day prognosis (P<0.05). ROC curve and 28 day survival curve showed that the area under ROC curve of DeltaPVPI predicting prognosis of patients with ARDS was 0.812, when the optimal cut off value was 1.2, and the median survival period in DeltaPVPI>1.2 group was longer than that in the Delta PVPI<=1.2 group. CONCLUSIONS: The continuous dynamic observation of EVLWI and PVPI changes is better than that of a single detection. DeltaEVLWI and DeltaPVPI are independent risk factors and can be used as an auxiliary indicator for the prognosis of patients with ARDS. PMID- 26814111 TI - [Effect of transpulmonary pressure-directed mechanical ventilation on respiration in severe acute pancreatitis patient with intraabdominal hypertension]. AB - OBJECTIVE: To assess the effect of mehanical ventilation (MV) guided by transpulmonary pressure (Ptp) on respiratory mechanics and gas exchange in severe acute pancreatitis patient with intraabdominal hypertension. METHODS: Twelve severe acute pancreatitis patient with intraabdominal hypertension and acute respiratory distress syndrome(ARDS) underwent mechanical ventilation were involved from Jan to Dec 2013. PEEP levels were set to achieve a Ptp of 0 to 10 cm of water at end expiration. We also limited tidal volume to keep Ptp at less than 25 cm of water at end inspiration. Respiratory mechanics and gas-exchange were measured. RESULTS: Plat pressure (Pplat) increased and the compliance of chest wall (Ccw) decreased when intraabdominal pressure (IAP) increased. Pplat correlated with IAP positively (r2=0.741 9, P<0.05) and Ccw? correlated with IAP negtively (r2=0.722 2, P<0.05), respectively.There were not corrletions between IAP and end-expiratory Ptp (Ptp-e) and end-inspiratory Ptp (Ptp-i) (P>0.05). Compared with baseline, after guiding MV with Ptp, the Level of PEEP (14.6+/-4.2) cmH2O vs (8.3+/-2.0) cmH2O, and Ptp-e (1.5+/-0.5) cmH2O vs (-2.3+/-1.4) cmH2O increased (P<0.05) and Ptp-i did not increase significantly (P>0.05). Ptp-e correlated with PEEP (r2=0.549, P<0.05) and end-expiratory esophageal pressure (Pes-e) (r2=0.260, P<0.05). Ptp-i correlated with Pplat (r2=0.523, P<0.05) and end-inspiratory esophageal pressure (Pes-i) (r2=0.231, P<0.05), but did not correlate with Tidal volume(VT) (r2=0.052 4, P>0.05). Compared with baseline, lung compliance (CL) (48.1+/-10.3) cmH2O vs (25.7+/-6.4) cmH2O and oxygenation index (PaO2/FiO2) (235+/-48) mmHg vs (160+/-35) mmHg improved obviously (P<0.05), dead space fraction (VD/VT) (0.48+/-0.07) vs (0.59+/-0.06) decreased (P<0.05), but Ccw and respiratory compliance(Cr) didn't improve (P>0.05). CONCLUSIONS: Transpulmonary pressure-directed mechanical ventilation in ARDS secondary to severe acute pancreatitis patient with intraabdominal hypertension could not only recruit the collapsed alveoli, improve lung compliance, increase oxygenation index and decrease dead space ventilation but also monitor lung stress to avoid alveoli overinflation, which might be lung protective. PMID- 26814112 TI - [Score in APACHEIIderived from critical clinic information system is more accurate than artificial method]. AB - OBJECTIVE: To evaluate the accuracy of APACHEII score derived from critical clinic information system compared with artificial method. METHODS: The APACHEII score derived from critical clinical information system (simple called system score) from August 1st to September 1st 2013 were collected.Each of the results including overall score subtitle were compared with the corresponding score calculated through artificial method. RESULTS: there is big difference between the two methods both between overall score and subtitle score.overall score (193.4) vs.(127.6) (P=0.001); age: (161.4) vs.(159.6) (P=0.862); Temperature: (169.6) vs.(151.4) (P=0.027); MAP: (190.8) vs. (130.2) (P=0.001); HR: (181.8) vs.(139.3) (P=0.001); RR: (191.4) vs.(129.6) (P=0.001); PaO2: (152.5) vs. (168.5) (P=0.001); pH: (174.0) vs. (147.0) vs. (P=0.001); Na+: (161.5) vs.(159.6) (P=0.576); K+: (163.4) vs. (157.6) (P=0.457); CR: (177.2) vs (143.8) (P=0.001); HCT: (166.2) vs. (154.8) (P=0.199); WBC: (167.8) vs.(153.2) (P=0.054); Items of GCS and Organ Failure were not being compared. CONCLUSION: The APACHEII score obtained from critical clinic information system is more accurate and more objective. PMID- 26814113 TI - [Regulation of hydrogen sulfide on transporter protein Bsep and Mdr2 in acute liver failure]. AB - OBJECTIVE: To observe the effect of hydrogen sulfide on Bsep and Mdr2 in acute liver failure induced by thioacetamide. METHODS: Twenty-four male SD rats were randomly divided into thioacetamide (TAA) induced model group (n=6), control group (n=6), TAA+sodium hydrosulfide group (n=6), and TAA+ propargylglycine group (n=6). TAA was given to enterocoelia at the dose of 600 mg/kg for the model group, sodium hydrosulfide group and propargylglycine group rats.Sodium hydrosulfide with the dose of 0.15 mmol/kg and propargylglycine of 30 mg/kg was injected into enterocoelia one hour before the TAA used. All rats were sacrificed and serum specimen was collected to test hydrogen sulfide and hepatic function. The method of Western blot and Immunohistochemistry were used to measure the expression of Bsep and Mdr2 in the liver. RESULTS: The Liver function of TAA group rats was severely injured [ALT(524.0+/-32.0) vs (28.3+/-8.4) U/L]. It was worsen by application of sodium hydrosulfide [ALT(861.9+/-55.1) U/L] while recovered [ALT(59.5+/-10.2) U/L)] by propargylglycine. The level of bilirubin and bile acid was significantly higher in the TAA group rats than in the normal control group, and the application of sodium hydrosulfide caused bile acids increased further besides of bilirubin. On the contrary, the levels of bile acids and bilirubin were significantly decreased with PPG application. The level of hydrogen sulfide in the serum of the TAA group rats was higher than normal group rats'. That was elevated by sodium hydrosulfide and decreased by propargylglycine.Severely edema, necrosis and inflammatory cell infiltration were observed in TAA group rats, which worse by sodium hydrosulfide and released by propargylglycine. The expression of Bsep and Mdr2 down regulated in TAA and deteriorated by sodium hydrosulfide application and relieved by propargylglycine application. CONCLUSION: Hydrogen sulfide exacerbated the Bsep and Mdr2 loss in the liver failure and contributed to high serum concentration of bile acids. PMID- 26814114 TI - [Rosiglitazone protects against endotoxin-induced acute liver injury in rats]. AB - OBJECTIVE: To observe the effects of rosiglitazone (ROSI) on endotoxin-induced acute liver injury in rats. METHODS: All the animals were randomly assigned to one of four following groups (n=24 per group). Rats in the Sepsis-Dimethyl sulfoxide (DMSO) group(n=24), rats were treated with 10%DMSO(1 ml/kg) 30 mins before they were challenged with cecal ligation and puncture(CLP) (n=24). In the sepsis-rosiglitazone (ROSI) group was identical to the sepsis-DMSO group but received ROSI (10 mg/kg intravenously) (n=24). In the sham-DMSO group, rats were treated with 10% DMSO(1 ml/kg) 30 mins before the administration of saline (n=24). The sham-ROSI group was identical to the sham-ROSI group except that ROSI (10 mg/kg intravenously) was administered instead of DMSO (n=24). Sepsis was induced in rats by dissecting the cecum and placing the discontinued organ back into the abdomen CLP. And all the Rats were decapitated at 0, 6, 12, 24 h after the model completed.Serum glutamic oxaloacetic transaminase(GOT), glutamic pyruvic transaminase (GPT), interleukin 12 (IL-12) were determined to assess activity and liver pathologic change of rats in different groups. Data were analyzed with SPSS 19.0 software.Student's t-test was used to compare densitometry data. RESULTS: SPSS 19.0 statistical software analysis by the outcome of the application ELASA method for determining zero hours between every group, there was non-difference. The sepsis-ROSI group and the sepsis-DMSO group 12 hours and 24 hours the presence of plasma GOT concentration changes statistically significant difference (t12=3.97, P12=0.01; t24=3.10, P24<0.001), (t12=0.55, P12<0.001; t24=4.32, P24<0.001). The Sepsis-ROSI group and the sepsis DMSO group 6 hours, 12 hours and 24 hours the presence of plasma GPT concentration changes statistically significant difference (t6=3.17, P6=0.021; t12=2.81, P12=0.018; t24=5.06, P24<0.001), (t6=2.67, P6=0.001; t12=3.36, P12=0.002; t24=2.83, P24<0.001). The sepsis-ROSI group and the sepsis-DMSO group 6 hours, 12 hours and 24 hours the presence of plasma IL-12 concentration changes statistically significant difference(t6=3.17, P6=0.021; t12=2.81, P12=0.018; t24=5.06, P24<0.001), (t6=2.67, P6=0.001; t12=3.36, P12=0.002; t24=2.83, P24<0.001). Sepsis GOT, GPT, IL-12 began to increase in 6 hours, 24 hours of high value, no clear peak trend, the sepsis-ROSI group compared with the sham-ROSI group had lower concentrations of GOT, GPT and IL-12 to some extent. Description rosiglitazone inhibit inflammatory cytokines in rats with sepsis role of IL-12, there is a certain role to reduce the inflammatory response in sepsis. CONCLUSIONS: Treatment with Thiazolidinedione, markedly inhibited the expression of IL-12, attenuated pulmonary inflammation and liver injury caused by sepsis in rat. PMID- 26814115 TI - [Multi-dimensional exploration of the characteristics of emotional regulation in children with attention-deficit/hyperactivity disorder]. AB - OBJECTIVE: To explore the characteristics of emotional regulation in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Two hundred and eighty-two children who were diagnosed as ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) were recruited from the child psychiatric clinic of Peking University Sixth Hospital/Institute of Mental Health from August 2012 to April 2014. And 260 normal children from the local primary schools were selected as the healthy control group. The emotional factors or items of Conners' Parent Rating Scale, Behavior Rating Inventory of Executive Function (BRIEF), Achenbach's Child Behavior Checklist (CBCL) and Rutter Children Behavior Questionnaire were used to assess the characteristics of emotional regulation multi-dimensionally. RESULTS: After controlling for the effects of age, sex and intelligence quotient (IQ), in Conner scale, the emotional lability (EL) scores of ADHD group were significantly higher than that of healthy control group [(4.3+/-2.6) vs (1.4+/-1.5), P<0.001]. In BRIEF scale, the emotional control (ECTRL) scores of ADHD group were significantly higher than that of control group [(16.1+/-4.4) vs (12.0+/-2.5), P<0.001]. In CBCL scale, the deficient emotional self-regulation (DESR) scores of ADHD group were significantly higher than that of control group [(26.8+/-11.0) vs (6.6+/-6.8), P<0.001]. In Rutter questionnaire, the emotional symptoms (ES) scores of ADHD group were significantly higher than that of control group [(2.7+/-2.0) vs (1.7+/ 1.5), P<0.001]. Based on the receiver operating characteristics (ROC) curve, the area under the curve (AUC) of EL was 0.84 with 95% Confidence Intervals (CI) 0.81 0.87. The AUC of ECTRL was 0.81 with 95%CI 0.77-0.84. The AUC of DESR was 0.95 with 95%CI 0.93-0.97. The AUC of ES was 0.66 with 95%CI 0.61-0.70. CONCLUSIONS: The study multi-dimensionally indicated that children with ADHD displayed significant deficient emotional regulation. PMID- 26814116 TI - [The resting-state functional connectivity of the hypothalamus and its relationships with gonadal steroid hormones and depression symptoms in perimenopausal women]. AB - OBJECTIVE: This study aimed to investigate the resting-state functional connectivity of the hypothalamus and its relationships with gonadal steroid hormones and depression symptoms in perimenopausal women. METHODS: Total 66 perimenopausal women voluntarily participated in this study from October 2012 to June 2013. Zung Self-rating Depression Scale (ZSDS) was used to assess depression symptoms. Plasma gonadal steroid hormones including estradiol, testosterone, and progesterone were determined by the chemiluminescence immunoassay. A 3.0 Tesla magnetic resonance imaging (MRI) scanner was utilized to acquire resting-state functional MRI data. The z-value functional connectivity map of each participant was calculated voxel-wisely based on the seed region of the hypothalamus. One sample t test of Statistical Parametric Mapping (SPM) were used to determine the brain areas with statistically significant functional connectivity to the hypothalamus, then multiple regression of SPM was used to calculate the correlated areas with 3 gonadal steroid hormones, respectively. Finally, Pearson correlation was performed to analyze bivariate correlations between mean z-values and ZSDS scores. RESULTS: Significant functional connectivity to the hypothalamus were found in brain areas as follows:the lateral inferior frontal gyrus, medial prefrontal cortex, dorsal lateral prefrontal cortex, orbitofrontal cortex, subgenual cortex, anterior cingulate cortex, posterior cingulate cortex, cuneus and precuneus, hippocampus and parahippocampal gyrus, and angular gyrus (False Discovery Rate q<0.05). Among these areas, the plasma testosterone level was positively related to the functional connectivity strength of the right angular gyrus, and negatively related to the strengths of the right subgenual cortex and bilateral medial superior frontal gyrus to the hypothalamus (PAlphaSim<0.05). Especially, mean z-value in the subgenual cortex was positively related to the ZSDS index score (r=0.279, P=0.023), and factor scores of the core depression symptoms (r=0.278, P=0.024) and somatic symptoms (r=0.357, P=0.003). CONCLUSION: In perimenopausal women, the hypothalamus has resting-state functional connectivity with widespread areas involved in the brain depression-related network and default mode network, and the plasma androgen level may modulate the functional connectivity strengths of the hypothalamus and decrease the susceptibility of perimenopausal women to depression. PMID- 26814117 TI - [Altered cortical and subcortical local coherence in migraine with and without aura:evidence from resting-state fMRI]. AB - OBJECTIVE: To compare the interictal spontaneous brain activity between migraine without aura (MwoA) patients, Migraine with visual aura (MA) patients and healthy control subjects in order to provide further insights into the complex migraine pathophysiology. METHODS: Twenty-three eligible MwoA patients, twelve MA patients who were treated in the neurology clinics in the Second Hospital of Hebei Medical University from March to October 2014 and twenty-five gender-, age- and education matched healthy volunteers participated in this study.After demographic and clinical characteristics were acquired, a 3.0-T MRI system was used to obtain rfMRI.ReHo method was applied to analyze the synchronization of the BOLD signal in the same time series among neighboring voxels of the brain. RESULTS: Compared with healthy controls, MwoA patients showed significant decreases in ReHo values in the right thalamus, right putamen, right prefrontal lobe and right hippocampus (P<0.05); while MA patients showed significant decreases in ReHo values in the right thalamus, right putamen, right cerebellum and brainstem, whereas a significant increase in ReHo values in the right occipital lobe (P<0.05). Furthermore, compared with MA patients, increased ReHo values in the right cerebellum and brainstem were shown in the MwoA group (P<0.05). CONCLUSIONS: The results suggest that the resting-state abnormalities of these regions may be associated with functional impairments in pain processing in migraine.Specifically, the results of brain regions may reflect both the similarities and differences of pathophysiological mechanisms relative to the major subtypes of migraine. PMID- 26814118 TI - [Value of diffusion-weighted MRI in differentiation between benign and malignant polypoid gallbladder lesions]. AB - OBJECTIVE: To evaluate the efficiency of diffusion-weighted MRI in differentiating between benign and malignant polypoid gallbladder lesions. METHODS: The study population consisted of 10 benign (5 polyps, 3 adenomyomatosis and 2 adenomas) and 13 malignant (all adenocarcinomas) polypoid gallbladder lesions treated in hospital from November 2007 to May 2014. DWI was evaluated by two observers. Qualitatively, the signal intensity of the lesions on DWI was visually evaluated and categorized as iso, high, or very high signal.Quantitatively, the ADC values of the lesions were measured from ADC maps. Statistical analysis was performed using a two-tailed Fisher's exact test and the Mann-Whitney test, respectively. The cut-off values were determined by receiver operating characteristic analysis. RESULTS: Qualitative analysis revealed a statistical difference (P=0.036). In the 10 benign lesions, three were categorized as iso, 5 as high, and 2 as very high signal.Four of the 13 malignant lesions were categorized as high, and the remaining 9 were categorized as very high signal. The mean ADC value of the malignant lesions [(1.13+/-0.28)*10(-3) mm2/s] was significantly lower than that of benign lesions [(2.22+/-0.42)*10(-3) mm2/s, P<0.01]. The cut-off value between cancer and the benign lesions was 1.5*10(-3) mm2/s, the sensitivity, specificity, and accuracy were 92%, 100% and 96%, respectively. CONCLUSION: Diffusion-weighted MRI may be useful in differentiating between benign and malignant polypoid gallbladder lesions. PMID- 26814119 TI - [Mechanical thrombectomy using Solitaire AB stent for acute middle cerebral artery occlusion with atrial fibrillation]. AB - OBJECTIVE: To investigate the endovascular management strategy of mechanical thrombectomy using Solitaire AB stent for acute middle cerebral artery occlusion with atrial fibrillation and assess the safety and efficacy. METHODS: From June 2012 to Dec 2013, 40 patients of acute middle cerebral artery occlusion with atrial fibrillation admitted to our institutes were treated by Solitaire AB stent.Clinical status was evaluated by the score of National Institute of Health Stroke Scale (NIHSS) before and 72 hours after treatment, immediate scale of thrombolysis in cerebral infarction (TICI) after thrombectomy, the 90 d score of Modified Rankin Scale (mRS).The patients were classified into good result group (mRS<=2) and bad result group (mRS>2) according to the mRS score. RESULTS: Out of 40 cases, there were 28 cases caused by cardiogenic embolism. Recanalization was successful (TICI score 2b or 3) in 37 out of 40 (92.5%). 90 d follow-up mRS was 0 2 in 19 of 40 patients (47.5%). 3-5 in 21 patients (52.5%). 5 patients died (12.5%).Symptomatic hemorrhagic transform developed in 6 patients (15%).No complications related to the Solitaire AB thrombectomy occurred.Mean time from symptom onset to recanalization (312+/-52 min vs 370+/-68 min, P<0.05) and initial NIHSS score (17.0+/-0.4 vs 18.6+/-0.4, P<0.05) were of significant difference between good result group and bad result group. CONCLUSION: These results confirm that mechanical thrombectomy using solitaire AB stent for acute middle cerebral artery occlusion with atrial fibrillation is safe and effective. PMID- 26814120 TI - [Surgical treatment of intracranial aneurysms via the pterional keyhole approach]. AB - OBJECTIVE: Modify the pterional approach for intracranial aneurysms clipping with minimally invasive concept to reduce the risk of iatrogenic surgical trauma. METHODS: A 4.0 cm skin incision was made along the temporal hairline and centered on the pterion, temporal muscle was incised along the sylvian fissure.A bone flap with 2.0 to 2.5 cm in diameter was milled after a bone hole was drilled just on the sphenoid ridge, which was drilled off as needed then.Aneurysms were exposed after dissection of sylvian fissure and cistern, as well as cerebrospinal fluid releasing.A total of 123 cases with 140 intracranial aneurysms were treated surgically via the pterional keyhole approach, including 6 large aneurysms, 4 giant aneurysms, and 17 cases with multiple aneurysms (34 aneurysms). Of 3 cases with bilateral aneurysms, 2 were treated via bilateral approach as well as 1 via unilateral approach. Contralateral approach was used in 1 case with ophthalmic artery aneurysm, which pointed medial. Concomitant intracranial tumors were removed simultaneously in 2 cases, and one of them was diagnosed with middle cerebral artery aneurysm and tuberculum sellae meningioma, the other one with posterior communicating artery aneurysm and middle cranial fossa menigioma. RESULTS: Of the 140 aneurysms, 139 aneurysms were clipped and 1 was trapped.Postoperative image showed 4 cases had residual of aneurysm neck. 3 cases had incomplete dysfunction of oculomotor nerve and 1 had mild hemiplegia after surgery and recovered eventually. 4 cases presented with aggravated disturbance of consciousness, of whom 3 cases were caused by ischemia and 1 by brain edema.Unusual ipsilateral hemiplegia occurred in 1 case in Hunt&Hess grade IV, which caused by contralateral vasospasm. Postoperative courses in other cases were uneventful. CONCLUSIONS: As a minimally invasive and effective approach, the pterional keyhole approach is applicable to intracranial aneurysms clipping for patients without any necessary for decompressive craniectomy. Surgical related complications and operative duration can be reduced significantly. PMID- 26814121 TI - [Diagnosis and surgical management in patients with Cushing disease with negative magnetic resonance imaging]. AB - OBJECTIVE: To analyze the outcome in patients who underwent transsphenoidal surgery (TSS) with Cushing's disease (CD) with no visible adenoma on magnetic resonance imaging (MRI). METHODS: Between 2012 and 2014, 118 patients with CD underwent TSS at PUMCH. We retrospectively analyzed data in 43 patients without visible adenomas on MRI and compared them with 75 patients with MRI-visible microadenomas. RESULTS: Of 75 patients with MRI-visible microadenomas, postoperative remission was achieved in 64 patients (85.3%), and no recurrence or persistent of CD was observed during 2-year follow-up, and pituitary adenoma confirmed by pathology examination in 71 cases.Of 43 patients with negative MRI, postoperative remission was achieved in 32 patients (74.4%), and pituitary adenoma confirmed by pathology examination in 38 cases. No statistic difference was found between MRI-negative group and MRI-visible group after chi2 test (P value>0.05). BIPSS was performed in 32 cases, and 27 cases were positive. Pituitary adenoma was confirmed in 28 cases. CONCLUSION: There is no difference in remission rate of CD in MRI-visible and MRI-negative group. BIPSS should be performed in normal MRI cases. We recommend transsphenoidal surgery as the first line treatment for CD. Selective adenomectomy was recommended when an adenoma was found during surgery, and partial or hemihypophysectomy when no adenoma was found. PMID- 26814122 TI - [Analysis of relevant factors affecting the visual prognosis of traumatic optic neuropathy]. AB - OBJECTIVE: To investigate the relevant factors affecting the prognosis of traumatic optic neuropathy (TON). METHODS: A total of 685 cases (719 eyes) of TON from June 2007 to June 2012 were analyzed retrospectively. A total of 9 independent variables (X) including sex, side of TON, duration of coma, vision after trauma, fracture of optic nerve canal, fracture of big ridge of sphenoid bone, hematoma in sphenoid sinus and surgical treatment, and the dependent variable (Y) of visual prognosis were analyzed using the unconditioned Logistic regression analysis to find the risk factors for the visual prognosis of TON. RESULTS: A total of 325 eyes (45.2%) recovered out of 719 eyes. Four variables showed a significant relation with the visual recovery: duration of coma>0.5 h (X3, P<0.01), remnant vision after trauma (X4, P<0.01) and sphenoid ridge fractures (X7, P<0.01), and surgical treatment (X9, P<0.01). These factors above were also proved to be significant in Logistic regression. CONCLUSION: The duration of coma>0.5 h, no light perception after trauma, sphenoid ridge fractures are risk factors of visual recovery, while surgical treatment is the protective factor for the visual recovery after TON. PMID- 26814123 TI - [Clinical value of toes periungual green-coloured voxels of dual-energy CT gout detecting technology]. AB - OBJECTIVE: To evaluate the clinical value of dual-energy CT(DECT) in the detection of green-coloured voxels in toenails in patients with gout using DECT. METHODS: A total of 53 patients with gout could be included in the study composed of 45 men and 8 women, and 33 individuals without gout were regarded as control group. There were no significant differences in gender and age between two groups. DECT were performed for the both feet, DE (80 kV and 140 kV) datasets were reconstructed via gout-recognition software, the pseudo-color images group as the postprocessed group.Imagings were reviewed independently by two senior radiologists. Chi-square test was used for statistical analysis with the SPSS 17.0 software. RESULTS: In the gout group, DECT scans revealed a total of 266 areas of green-coloured voxels in 53 patients (relevance ratio 50.2% (266/530)); in the control group, 27 areas of green-coloured voxels were detected in 33 patients (relevance ratio 8.2% (27/330)), the differences had statistical significance (P<0.01). In the gout group, the green-coloured voxels were detected only in the nail groove in 8 patients which compared with 2 the control group, the differences had statistical significance (P<0.01). CONCLUSIONS: DECT gout recognition technology can detect green-coloured voxels of monosodium urate in the toenails, with a great potential in clinical diagnosis. PMID- 26814124 TI - [Effect of LINGO-1 gene silencing on movement function of EAE mice]. AB - OBJECTIVE: To explore the effect of LINGO-1 silencing on movement function of experimental autoimmune encephalomyelitis (EAE) mice. METHODS: EAE was established by induction of MOG35-55 in female C57/BL6 mice. Then female EAE mice (n=105) were completely randomly divided into 5 groups: group A (n=21): 5 ul 5*10(9) Tu/ml lentiviral vectors encoding LINGO-1shRNA (LV/LINGO-1-shRNA) by intracerebroventricular (ICV) injection, group B (n=21): 5 ul 5*10(8)Tu/ml LV/LINGO-1-shRNA by ICV injection, group C (n=21): 5 ul 5*10(7) Tu/ml LV/LINGO-1 shRNA by ICV injection, group D (n=21): 5 ul LVCON053 by ICV injection and group E (n=21): untreated.The movement function was scored and the expression of LINGO 1 protein was detected by Western blot on day 1, 3, 7, 14, 21, 30 after ICV among different groups. Luxol fast blue staining was performed to know about conditions of myelin sheath on day 30. RESULTS: The expression of LINGO-1 in EAE mouse was obviously downregulated ever since day 7 after LV/LINGO-1-shRNA implantation.Group B and C achieved the most reduction of LINGO-1 expression (1.99+/-0.13, 2.08+/-0.10, P<0.05, P<0.01). Simultaneously, the movement functional score of group A, B and C was lowered at different levels from day 7 (3.11+/-0.13, 2.42+/-0.13, 2.96+/-0.10 vs 3.56+/-0.15, 3.87+/-0.12, P<0.01, P<0.01, P<0.05), with the most marked decrease in group B. The densities of myelin sheaths in group A and B were higher than untreated group on day 30 (0.72+/-0.09, 0.83+/-0.11 vs 0.56+/-0.10, P<0.05, P<0.01). CONCLUSION: LV/LINGO 1shRNA by ICV injection is an effective method to silence LINGO-1 expression. LINGO-1 silencing could ameliorate motor function and promote formation of myelin sheaths. But the effects do not enhance with the increase of LV/LINGO-1-shRNA dose. PMID- 26814125 TI - [Evaluate the early changes of renal ischemia-reperfusion by susceptibility weighted imaging:primary experiment study]. AB - OBJECTIVE: To explore whether susceptibility weighted imaging (SWI) could diagnose the early changes of renal IRI in vivo by modeling the renal ischemia reperfusion (IRI) of rabbit. METHODS: Thrity four New Zealand white rabbits were chosen, the vesseles of the left kidney of rabbits were ligated for 60 minutes, then the renal ischemia-reperfusion model was established. Respectively, the rabbits before ligation, 0.5, 24 and 48 h after the ligation, were examined with MR, then the signal of the cortex and medulla was analyzed in SWI and T2WI, the imaging features were compared with histopathology. RESULTS: The inner medullary of renal showed high signal, low signal in the outer medulla and mildly high in the cortex before ligation in T2WI sequence, which showed the typical three-band signal distribution, while the outer medulla showed wildly hypo-signal in SWI, the remnants showed high signal; kidney swelled significantly 0.5 hour after ligation, the stripe of cortex became thin, however, the inner medulla and outer medulla widened. The hypo-signal of the outer medulla faded, while the signal of inner medullary and cortical slightly elevated. The signal intensity of outer medulla lowered more obviously in SWI, the margin of the cortex and medulla became more clearly 24 and 48 h after ligation,However the signal of the outer medulla was higher than normal kidney in the SWI, and punctuate or stripe haemorrhage occurred in the outer medulla. Respectively, the number of punctuate, stripe haemorrhage detected by SWI in the out medulla of kidney 0.5, 24 and 48 h after ligation were 0, 2.50, 6.75 (F=52.17, P<0.01), Meanwhile, the number detected by T2WI was 0, 1.13, 2.88 (F=15.65, P<0.01); the number of hemorrhage which was detected by SWI and T2WI in the outer medulla among different timepoint have the statistical significance (t=4.83, P<0.01). CONCLUSION: SWI can clearly show early changes in IRI-renal, especially in the outer medulla of the renal, the technique was helpful to assess the early changes of renal IRI. PMID- 26814126 TI - A Hox Gene, Antennapedia, Regulates Expression of Multiple Major Silk Protein Genes in the Silkworm Bombyx mori. AB - Hoxgenes play a pivotal role in the determination of anteroposterior axis specificity during bilaterian animal development. They do so by acting as a master control and regulating the expression of genes important for development. Recently, however, we showed that Hoxgenes can also function in terminally differentiated tissue of the lepidopteranBombyx mori In this species,Antennapedia(Antp) regulates expression of sericin-1, a major silk protein gene, in the silk gland. Here, we investigated whether Antpcan regulate expression of multiple genes in this tissue. By means of proteomic, RT-PCR, and in situ hybridization analyses, we demonstrate that misexpression of Antpin the posterior silk gland induced ectopic expression of major silk protein genes such assericin-3,fhxh4, and fhxh5 These genes are normally expressed specifically in the middle silk gland as is Antp Therefore, the evidence strongly suggests that Antpactivates these silk protein genes in the middle silk gland. The putativesericin-1 activator complex (middle silk gland-intermolt-specific complex) can bind to the upstream regions of these genes, suggesting that Antpdirectly activates their expression. We also found that the pattern of gene expression was well conserved between B. moriand the wild species Bombyx mandarina, indicating that the gene regulation mechanism identified here is an evolutionarily conserved mechanism and not an artifact of the domestication of B. mori We suggest that Hoxgenes have a role as a master control in terminally differentiated tissues, possibly acting as a primary regulator for a range of physiological processes. PMID- 26814127 TI - Arf-like Protein 3 (ARL3) Regulates Protein Trafficking and Ciliogenesis in Mouse Photoreceptors. AB - Arf-like protein 3 (ARL3) is a ubiquitous small GTPase expressed in ciliated cells of plants and animals. Germline deletion ofArl3in mice causes multiorgan ciliopathy reminiscent of Bardet-Biedl or Joubert syndromes. As photoreceptors are elegantly compartmentalized and have cilia, we probed the function of ARL3 (ADP-ribosylation factor (Arf)-like 3 protein) by generating rod photoreceptor specific (prefix(rod)) and retina-specific (prefix(ret))Arl3deletions. In predegenerate(rod)Arl3(-/-)mice, lipidated phototransduction proteins showed trafficking deficiencies, consistent with the role of ARL3 as a cargo displacement factor for lipid-binding proteins. By contrast,(ret)Arl3(-/-)rods and cones expressing Cre recombinase during embryonic development formed neither connecting cilia nor outer segments and degenerated rapidly. Absence of cilia infers participation of ARL3 in ciliogenesis and axoneme formation. Ciliogenesis was rescued, and degeneration was reversed in part by subretinal injection of adeno-associated virus particles expressing ARL3-EGFP. The conditional knock-out phenotypes permitted identification of two ARL3 functions, both in the GTP-bound form as follows: one as a regulator of intraflagellar transport participating in photoreceptor ciliogenesis and the other as a cargo displacement factor transporting lipidated protein to the outer segment. Surprisingly, a farnesylated inositol polyphosphate phosphatase only trafficked from the endoplasmic reticulum to the Golgi, thereby excluding it from a role in photoreceptor cilia physiology. PMID- 26814129 TI - Megakaryocytic Maturation in Response to Shear Flow Is Mediated by the Activator Protein 1 (AP-1) Transcription Factor via Mitogen-activated Protein Kinase (MAPK) Mechanotransduction. AB - Megakaryocytes (MKs) are exposed to shear flow as they migrate from the bone marrow hematopoietic compartment into circulation to release pro/preplatelets into circulating blood. Shear forces promote DNA synthesis, polyploidization, and maturation in MKs, and platelet biogenesis. To investigate mechanisms underlying these MK responses to shear, we carried out transcriptional analysis on immature and mature stem cell-derived MKs exposed to physiological shear. In immature (day (d)9) MKs, shear exposure up-regulated genes related to growth and MK maturation, whereas in mature (d12) MKs, it up-regulated genes involved in apoptosis and intracellular transport. Following shear-flow exposure, six activator protein 1 (AP-1) transcripts (ATF4,JUNB,JUN,FOSB,FOS, andJUND) were up-regulated at d9 and two AP-1 proteins (JunD and c-Fos) were up-regulated both at d9 and d12. We show that mitogen-activated protein kinase (MAPK) signaling is linked to both the shear stress response and AP-1 up-regulation. c-Jun N-terminal kinase (JNK) phosphorylation increased significantly following shear stimulation, whereas JNK inhibition reduced shear-induced JunD expression. Although p38 phosphorylation did not increase following shear flow, its inhibition reduced shear-induced JunD and c-Fos expression. JNK inhibition reduced fibrinogen binding and P-selectin expression of d12 platelet-like particles (PLPs), whereas p38 inhibition reduced fibrinogen binding of d12 PLPs. AP-1 expression correlated with increased MK DNA synthesis and polyploidization, which might explain the observed impact of shear on MKs. To summarize, we show that MK exposure to shear forces results in JNK activation, AP-1 up-regulation, and downstream transcriptional changes that promote maturation of immature MKs and platelet biogenesis in mature MKs. PMID- 26814130 TI - The Tumor-suppressive Small GTPase DiRas1 Binds the Noncanonical Guanine Nucleotide Exchange Factor SmgGDS and Antagonizes SmgGDS Interactions with Oncogenic Small GTPases. AB - The small GTPase DiRas1 has tumor-suppressive activities, unlike the oncogenic properties more common to small GTPases such as K-Ras and RhoA. Although DiRas1 has been found to be a tumor suppressor in gliomas and esophageal squamous cell carcinomas, the mechanisms by which it inhibits malignant phenotypes have not been fully determined. In this study, we demonstrate that DiRas1 binds to SmgGDS, a protein that promotes the activation of several oncogenic GTPases. In silico docking studies predict that DiRas1 binds to SmgGDS in a manner similar to other small GTPases. SmgGDS is a guanine nucleotide exchange factor for RhoA, but we report here that SmgGDS does not mediate GDP/GTP exchange on DiRas1. Intriguingly, DiRas1 acts similarly to a dominant-negative small GTPase, binding to SmgGDS and inhibiting SmgGDS binding to other small GTPases, including K Ras4B, RhoA, and Rap1A. DiRas1 is expressed in normal breast tissue, but its expression is decreased in most breast cancers, similar to its family member DiRas3 (ARHI). DiRas1 inhibits RhoA- and SmgGDS-mediated NF-kappaB transcriptional activity in HEK293T cells. We also report that DiRas1 suppresses basal NF-kappaB activation in breast cancer and glioblastoma cell lines. Taken together, our data support a model in which DiRas1 expression inhibits malignant features of cancers in part by nonproductively binding to SmgGDS and inhibiting the binding of other small GTPases to SmgGDS. PMID- 26814128 TI - Multidomain, Surface Layer-associated Glycoside Hydrolases Contribute to Plant Polysaccharide Degradation by Caldicellulosiruptor Species. AB - The genome of the extremely thermophilic bacterium Caldicellulosiruptor kronotskyensisencodes 19 surface layer (S-layer) homology (SLH) domain-containing proteins, the most in any Caldicellulosiruptorspecies genome sequenced to date. These SLH proteins include five glycoside hydrolases (GHs) and one polysaccharide lyase, the genes for which were transcribed at high levels during growth on plant biomass. The largest GH identified so far in this genus, Calkro_0111 (2,435 amino acids), is completely unique toC. kronotskyensisand contains SLH domains. Calkro_0111 was produced recombinantly inEscherichia colias two pieces, containing the GH16 and GH55 domains, respectively, as well as putative binding and spacer domains. These displayed endo- and exoglucanase activity on the beta 1,3-1,6-glucan laminarin. A series of additional truncation mutants of Calkro_0111 revealed the essential architectural features required for catalytic function. Calkro_0402, another of the SLH domain GHs inC. kronotskyensis, when produced inE. coli, was active on a variety of xylans and beta-glucans. Unlike Calkro_0111, Calkro_0402 is highly conserved in the genus Caldicellulosiruptorand among other biomass-degrading Firmicutes but missing from Caldicellulosiruptor bescii As such, the gene encoding Calkro_0402 was inserted into the C. besciigenome, creating a mutant strain with its S-layer extensively decorated with Calkro_0402. This strain consequently degraded xylans more extensively than wild-typeC. bescii The results here provide new insights into the architecture and role of SLH domain GHs and demonstrate that hemicellulose degradation can be enhanced through non-native SLH domain GHs engineered into the genomes of Caldicellulosiruptorspecies. PMID- 26814131 TI - Regulation of Phagolysosomal Digestion by Caveolin-1 of the Retinal Pigment Epithelium Is Essential for Vision. AB - Caveolin-1 associates with the endo/lysosomal machinery of cells in culture, suggesting that it functions at these organelles independently of its contribution to cell surface caveolae. Here we explored mice lacking caveolin-1 specifically in the retinal pigment epithelium (RPE). The RPE supports neighboring photoreceptors via diurnal phagocytosis of spent photoreceptor outer segment fragments. Like mice lacking caveolin-1 globally, (RPE)CAV1(-/-) mice developed a normal RPE and neural retina but showed reduced rod photoreceptor light responses, indicating that lack of caveolin-1 affects photoreceptor function in a non-cell-autonomous manner. (RPE)CAV1(-/-) RPE in situ showed normal particle engulfment but delayed phagosome clearance and reversed diurnal profiles of levels and activities of lysosomal enzymes. Therefore, eliminating caveolin-1 specifically impairs phagolysosomal degradation by the RPE in vivo. Endogenous caveolin-1 was recruited to maturing phagolysosomes in RPE cells in culture. Consistent with these in vivo data, a moderate increase (to ~ 2.5-fold) or decrease (by half) of caveolin-1 protein levels in RPE cells in culture was sufficient to accelerate or impair phagolysosomal digestion, respectively. A mutant form of caveolin-1 that fails to reach the cell surface augmented degradation like wild-type caveolin-1. Acidic lysosomal pH and increased protease activity are essential for digestion. We show that halving caveolin-1 protein levels significantly alkalinized lysosomal pH and decreased lysosomal enzyme activities. Taken together, our results reveal a novel role for intracellular caveolin-1 in modulating phagolysosomal function. Moreover, they show, for the first time, that organellar caveolin-1 significantly affects tissue functionality in vivo. PMID- 26814132 TI - Polymorphisms of the neurotrophic factor-3 (NTF-3) in Alzheimer's disease: rs6332 associated with onset time and rs6489630 T allele exhibited a protective role. AB - Because of its implications in neuroprotection, formation of long lasting memories and a disturbed function in Alzheimer's disease (AD), neurotrophin-3 (NTF-3) may represent an appropriate candidate gene conferring risk to AD. Recently, two single nucleotide polymorphisms (SNPs) (rs6489630 and rs6332) within the NTF-3 gene have been associated with AD in a Japanese population. Because of the importance of this finding, we analyzed the NTF-3 polymorphism in a Han Chinese sample consisting of 138 AD patients and 115 age-matched normal controls (NCs). In ApoE-E4 non-carriers, a negative gene dose-association was found between the A allele of rs6332 and the onset time of AD. Individuals homozygous for the A allele developed AD significantly earlier than those homozygous for the G allele (mean age +/- SD: 63.72 +/- 9.08 versus 69.75 +/- 6.03, p = 0.023). Moreover, in male subjects, we found the rs6489630 T allele to be protective against AD (OR 0.494; 95% CI 0.274-0.891; p value = 0.018) compared to C allele carriers. Due to a small number of patients showing homozygosity for the T allele in rs6489630 (n = 5), all of which were normal subjects, the result needs to be confirmed in a larger sample. The results suggest a gene dose association between the A allele of rs6332 and the onset of AD in E4 non carriers, as well as the NTF-3 rs6489630 polymorphism being a relevant risk factor for AD in patients lacking the ApoE-E4 allele in this Chinese sample. PMID- 26814133 TI - Six novel rare non-synonymous mutations for migraine without aura identified by exome sequencing. AB - Migraine without aura (MWO) is the most common among migraine group, and is mainly associated with genetic, physical and chemical factors, and hormonal changes. We aimed to identify novel non-synonymous mutations predisposing to the susceptibility to MWO in a Chinese sample using exome sequencing. Four patients with MWO from a family and four non-migraine subjects unrelated with these patients were genotyped using whole-exome sequencing. Bioinformatics analysis was used to screen possible susceptibility gene mutations, which were then verified by PCR. In four patients with MWO, six novel rare non-synonymous mutations were observed, including EDA2R (G170A), UBE2NL (T266G), GBP2 (A907G), EMR1 (C264G), CLCNKB (A1225G), and ARHGAP28 (C413G). It is worth stressing that GBP2 (A907G) was absent in any control subject. Multiple genes predispose to the susceptibility to MWO. ARHGAP28-, EMR1-, and GBP2-encoded proteins may affect angiokinesis, which supports vasogenic theory for the etiological hypothesis of this disease. CLCNKB-encoded protein may affect cell membrane potential, which is consistent with the cortical spreading depression theory. UBE2NL-encoded protein may regulate cellular responses to 5-hydroxytryptamine, which is in accordance with trigeminovascular reflex theory. EDA2R and UBE2NL are located on the X chromosome, which supports that this disease may have gender differences in genetic predisposition. Replication in larger sample size would significantly strengthen these findings. PMID- 26814135 TI - Microtubule-associated protein light chain 3 is involved in melanogenesis via regulation of MITF expression in melanocytes. AB - Although autophagy plays a role in melanogenesis by regulating melanosome degradation and biogenesis in melanocytes, a detailed understanding of the regulatory functions of autophagy factors is lacking. Here, we report a mechanistic link between microtubule-associated protein light chain 3 (LC3) activation and melanogenesis. We observed high expression of LC3 in melanosome associated pigment-rich melanocytic nevi of sun-exposed skin, as indicated by patterns of melanosomal protein MART1 expression. Rapamycin-induced autophagy significantly increased the melanin index, tyrosinase activity and expression of several proteins linked to melanosome biogenesis, including microphthalmia transcription factor (MITF), pre-melanosome protein and tyrosinase, in Melan-a melanocytes. siRNA-mediated knockdown of LC3, but not beclin-1 or ATG5, decreased melanin content and tyrosinase activity. LC3 knockdown also markedly inhibited MITF expression and subsequent rapamycin-induced melanosome formation. More importantly, LC3 knockdown suppressed alpha-MSH-mediated melanogenesis by attenuating cAMP response element-binding protein (CREB) phosphorylation and MITF expression in Melan-a cells via decreased extracellular signal-regulated kinase (ERK) activity. Overexpression of constitutively active ERK reversed the effect of LC3 knockdown on CREB phosphorylation and MITF expression. These findings demonstrate that LC3 contributes to melanogenesis by increasing ERK-dependent MITF expression, thereby providing a mechanistic insight into the signaling network that links autophagy to melanogenesis. PMID- 26814138 TI - Formation of tunable graphene oxide coating with high adhesion. AB - Graphene oxide (GO) can be applied as a coating on metals, but few of these coatings have an adhesion suitable for practical applications. We demonstrate here how to form a GO coating on metals with a high adhesion (~ 10.6 MPa) and tuneable surface, which can be further applied using similar/modified techniques for special applications (e.g. anti-corrosion and anti-biofouling). PMID- 26814136 TI - Determination of size-dependent metal distribution in dissolved organic matter by SEC-UV/VIS-ICP-MS with special focus on changes in seawater. AB - Iron is an essential micronutrient for all marine organisms, but it is also a growth limiting factor as the iron concentrations in the open ocean are below 1 nmol/L in sea water iron is almost entirely bound to organic ligands of the dissolved organic matter fraction, which are mostly of unknown structure. The input from rivers was traditionally considered as less important due to estuarine sedimentation processes of the mainly colloidal iron particles. However, recent studies have shown that this removal is not complete and riverine input may represent an important iron source in the open ocean. In this context, iron transport by land-derived natural organic matter (NOM), and dissolved organic matter (DOM) have been identified as carrier mechanisms for riverine iron. The aim of this work is to characterize complexes containing iron and other metals in waters simulating estuarine conditions in order to help understand which role iron-DOM compounds play in the open ocean. A method based on size-exclusion chromatography (SEC) with sequential UV/VIS and ICP-MS detection was developed for investigation of DOM size distribution and for assessment of the size dependent metal distribution in NOM-rich surface water. Furthermore, sample matrix experiments were also performed revealing a dependence of DOM size distribution upon seawater concentration and different compounds present in seawater. Finally, efforts toward determination of DOM size with standardization with typical SEC standards indicate that only relative comparisons are possible with this approach, and that the sample matrix composition strongly influences obtained results. PMID- 26814137 TI - Dysregulated expression of IDO may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration. AB - In pregnancy, trophoblast proliferation, migration and invasion are important for the establishment and maintenance of a successful pregnancy. Impaired trophoblast function has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy, but the underlying mechanisms remain unclear. Indoleamine 2,3-dioxygenase (IDO), an enzyme that catabolizes tryptophan along the kynurenine pathway, is highly expressed in the placenta and serum during pregnancy. Here, we identified a novel function of IDO in regulating trophoblast cell proliferation and migration. We showed that IDO expression and activity were decreased in unexplained recurrent spontaneous abortion (URSA) compared to normal pregnancy. Furthermore, blocking IDO in human trophoblast cells led to reduced proliferation and migration, along with decreased STAT3 phosphorylation and MMP9 expression. Increased STAT3 phosphorylation reversed the IDO knockdown-suppressed trophoblast cell proliferation and migration. In addition, the overexpression of IDO promoted cell proliferation and migration, which could be abolished by the STAT3 signaling inhibitor (AG490). Finally, we observed similar reductions of STAT3 phosphorylation and MMP9 expression in URSA patients. These results indicate that the level of IDO expression may be associated with pregnancy related complications, such as URSA, by affecting trophoblast cell proliferation and migration via the STAT3 signaling pathway. PMID- 26814139 TI - Effect of a CGMS and SMBG on Maternal and Neonatal Outcomes in Gestational Diabetes Mellitus: a Randomized Controlled Trial. AB - In this study, we sought to investigate the effects of a continuous glucose monitoring system (CGMS) on maternal and neonatal outcomes. A total of 106 women with gestational diabetes mellitus (GDM) in gestational weeks 24-28 were randomly allocated to the antenatal care plus CGMS group or the self-monitoring blood glucose (SMBG) group. The CGMS group was subdivided into early and late subgroups. There were no significant differences in prenatal or obstetric outcomes, e.g., caesarean delivery rate, Apgar score at 5 min, macrosomia or neonatal hypoglycaemia, between the CGMS and SMBG groups. The CGMS group had lower glycated haemoglobin (HbA1C) levels than the SMBG group; however, the difference was not statistically significant. The proportion of GDM women with excessive gestational weight gain was lower in the CGMS group than in the SMBG group (33.3% vs. 56.4%, P = 0.039), and women who initiated CGMS earlier gained less weight (P = 0.017). The mode of blood glucose monitoring (adjusted OR 2.40; 95% CI 1.030-5.588; P = 0.042) and pre-pregnancy BMI (adjusted OR 0.578; 95% CI 0.419-0.798; P = 0.001) were independent factors for weight gain. In conclusion, early CGMS for GDM mothers reduces gestational weight gain. A follow-up study with a large cohort is needed. PMID- 26814141 TI - Unraveling chronic obstructive pulmonary disease and keeping up with new and avatars of old occupational lung diseases. PMID- 26814142 TI - How to reduce hospital readmissions in chronic obstructive pulmonary disease? AB - PURPOSE OF REVIEW: This article examines factors associated with readmission for chronic obstructive pulmonary disease and interventions that may decrease readmissions. RECENT FINDINGS: The literature on this topic is relatively sparse. Drug therapy revolves around appropriate use of bronchodilators, antibiotics, and steroids. Patient education and participation and a multidisciplinary approach to the transition out of hospital can lead to decreased rehospitalizations. Patients who cannot participate in self-care may do better in skilled nursing facilities. SUMMARY: We must optimize in-hospital care and see that patients receive a continuum of care upon discharge. We must also recognize that some patients have received optimal care and yet continue to suffer with end-stage disease on an ongoing basis; palliative medications such as long-acting narcotics and end-of life discussions need to be considered in patients unable to survive for long outside of hospital. PMID- 26814140 TI - NF-kappaB promotes leaky expression of adenovirus genes in a replication incompetent adenovirus vector. AB - The replication-incompetent adenovirus (Ad) vector is one of the most promising vectors for gene therapy; however, systemic administration of Ad vectors results in severe hepatotoxicities, partly due to the leaky expression of Ad genes in the liver. Here we show that nuclear factor-kappa B (NF-kappaB) mediates the leaky expression of Ad genes from the Ad vector genome, and that the inhibition of NF kappaB leads to the suppression of Ad gene expression and hepatotoxicities following transduction with Ad vectors. Activation of NF-kappaB by recombinant tumor necrosis factor (TNF)-alpha significantly enhanced the leaky expression of Ad genes. More than 50% suppression of the Ad gene expression was found by inhibitors of NF-kappaB signaling and siRNA-mediated knockdown of NF-kappaB. Similar results were found when cells were infected with wild-type Ad. Compared with a conventional Ad vector, an Ad vector expressing a dominant-negative IkappaBalpha (Adv-CADNIkappaBalpha), which is a negative regulator of NF-kappaB, mediated approximately 70% suppression of the leaky expression of Ad genes in the liver. Adv-CADNIkappaBalpha did not induce apparent hepatotoxicities. These results indicate that inhibition of NF-kappaB leads to suppression of Ad vector mediated tissue damages via not only suppression of inflammatory responses but also reduction in the leaky expression of Ad genes. PMID- 26814143 TI - Quality of life changes over time in patients with chronic obstructive pulmonary disease. AB - PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is often considered to be a disease in which an inevitable decline in lung function results in increasing dyspnea and deteriorating quality of life. This review summarizes recent data that calls this classic paradigm into question. Studies evaluating the effects of chronic sputum production, physical activity, and inhaled medications on quality of life and prognosis are also discussed. RECENT FINDINGS: Chronic sputum production and level of dyspnea contribute at least as much to impairment of quality of life and prognosis as does abnormal lung function. An accelerated decline in FEV1 occurs in only half of the patients who develop COPD. Current pharmacotherapy has been shown to moderate disease progression and quality of life, although the effects are lost when inhaled corticosteroids are discontinued. Declining physical activity begins early in the course of COPD, but increasing activity levels result in improved quality of life and a slower decline in lung function. SUMMARY: Symptoms and activity levels are as important as measuring FEV1 in determining disease severity, quality of life, and prognosis of COPD. Therapies exist that moderate the course of the disease, and small sustained increases in physical activity may slow physical deterioration and improve health-related quality of life. PMID- 26814144 TI - The psychological burden of cystic fibrosis. AB - PURPOSE OF REVIEW: Cystic fibrosis (CF) is the most common genetic, life shortening illness among white populations. Management of the disease requires a complex, time-consuming treatment regimen. The purpose of this review is to highlight current research examining the psychological burden of CF, including psychological distress, social challenges, treatment burden, and adherence to daily treatments. RECENT FINDINGS: Individuals with CF and their parent caregivers report elevated symptoms of depression and anxiety. Recent international guidelines (Cystic Fibrosis Foundation and European Cystic Fibrosis Society) recommend annual screening of these symptoms using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scales. Symptoms of depression have been associated with decreased adherence, lower quality of life, and higher healthcare costs. Adherence to pulmonary medications has been found to be 50% or less and decreases with age. Poor adherence has been associated with higher healthcare costs, more frequent hospitalizations, and worse quality of life. SUMMARY: Individuals with CF face unique challenges that can lead to psychological burden. Screening for these symptoms and developing effective interventions to improve adherence are the key targets for the next 5 years of research. PMID- 26814146 TI - Core principles of sexual health treatments in cancer for men. AB - PURPOSE OF REVIEW: The considerable prevalence of sexual health problems in men after cancer treatment coupled with the severity of impact and challenges to successful intervention make sexual dysfunction one of the most substantial health-related quality of life burdens in all of cancer survivorship. Surgeries, radiation therapies, and nontreatment (e.g., active surveillance) variously result in physical disfigurement, pain, and disruptions in physiological, psychological, and relational functioning. Although biomedical and psychological interventions have independently shown benefit, long-term, effective treatment for sexual dysfunction remains elusive. RECENT FINDINGS: Recognizing the complex nature of men's sexual health in an oncology setting, there is a trend toward the adoption of a biopsychosocial orientation that emphasizes the active participation of the partner, and a broad-spectrum medical, psychological, and social approach. Intervention research to date provides good insight into the potential active ingredients of successful sexual rehabilitation programming. SUMMARY: Combining a biopsychosocial approach with these active intervention elements forecasts an optimistic future for men's sexual rehabilitation programming within oncology. However, significant gaps remain in our understanding of patient experience and appropriate sexual health intervention for gay men and men of diverse race and culture. PMID- 26814149 TI - Corrigendum: The conservation and signatures of lincRNAs in Marek's disease of chicken. PMID- 26814150 TI - Chemical Reactivity Probes for Assessing Abiotic Natural Attenuation by Reducing Iron Minerals. AB - Increasing recognition that abiotic natural attenuation (NA) of chlorinated solvents can be important has created demand for improved methods to characterize the redox properties of the aquifer materials that are responsible for abiotic NA. This study explores one promising approach: using chemical reactivity probes (CRPs) to characterize the thermodynamic and kinetic aspects of contaminant reduction by reducing iron minerals. Assays of thermodynamic CRPs were developed to determine the reduction potentials (ECRP) of suspended minerals by spectrophotometric determination of equilibrium CRP speciation and calculations using the Nernst equation. ECRP varied as expected with mineral type, mineral loading, and Fe(II) concentration. Comparison of ECRP with reduction potentials measured potentiometrically using a Pt electrode (EPt) showed that ECRP was 100 150 mV more negative than EPt. When EPt was measured with small additions of CRPs, the systematic difference between EPt and ECRP was eliminated, suggesting that these CRPs are effective mediators of electron transfer between mineral and electrode surfaces. Model contaminants (4-chloronitrobenzene, 2 chloroacetophenone, and carbon tetrachloride) were used as kinetic CRPs. The reduction rate constants of kinetic CRPs correlated well with the ECRP for mineral suspensions. Using the rate constants compiled from literature for contaminants and relative mineral reduction potentials based on ECRP measurements, qualitatively consistent trends were obtained, suggesting that CRP based assays may be useful for estimating abiotic NA rates of contaminants in groundwater. PMID- 26814151 TI - Episiotomy preferences, indication, and classification--a survey among Nordic doctors. AB - INTRODUCTION: Episiotomy performance impacts perineal health and rates of obstetric anal sphincter injuries (OASIS). Our objective was to assess self reported episiotomy practice and opinions on clinical indication for episiotomy among Nordic physicians and to investigate potential misclassification. MATERIAL AND METHODS: A survey was conducted among doctors attending the 2012 Nordic obstetrical and gynecological conference. Participants were asked to draw an episiotomy on a photo of a perineum with a crowning fetal head similarly to their clinical practice if an episiotomy was clinically indicated, and to name the technique drawn. Differences in outcome measures were compared by country of practice and seniority. RESULTS: The majority of the 297 participants (47%) drew a lateral episiotomy according to our classification by incision point and angle, but as many as 64% of these 138 doctors misclassified this as mediolateral episiotomy. Only 20% drew a mediolateral episiotomy, the great majority classifying it accurately, but 8% misclassified their mediolateral cut as a lateral episiotomy. One-third of episiotomies were nonclassifiable. In general, doctors in Finland, Sweden, and Norway more often favored lateral episiotomies compared with doctors in Denmark and Iceland. There were significant differences between Finnish and Norwegian vs. Danish and Swedish doctors in perception of clinical indications for episiotomy. CONCLUSIONS: The great variation in self reported episiotomy performance between Nordic physicians and large misclassification rates indicate that educational programs are warranted. Use of uniform classification and appropriate techniques may be crucial to investigate the role of episiotomies in preventing OASIS. PMID- 26814152 TI - An evaluation of multiple-schedule variations to reduce high-rate requests in the picture exchange communication system. AB - Using procedures similar to those of Tiger, Hanley, and Heal (2006), we compared two multiple-schedule variations (S+/S- and S+ only) to treat high-rate requests for edible items in the Picture Exchange Communication System (PECS). Two individuals with autism participated, after they showed persistent requests for edible items after PECS training. Stimulus control was achieved only with the multiple schedule that involved presentation of a discriminative stimulus during reinforcement components and its removal during extinction components (S+ only). Discriminated requests were maintained for the 1 participant who experienced schedule thinning. PMID- 26814148 TI - Mechanisms of resistance in castration-resistant prostate cancer (CRPC). AB - Despite advances in prostate cancer diagnosis and management, morbidity from prostate cancer remains high. Approximately 20% of men present with advanced or metastatic disease, while 29,000 men continue to die of prostate cancer each year. Androgen deprivation therapy (ADT) has been the standard of care for initial management of advanced or metastatic prostate cancer since Huggins and Hodges first introduced the concept of androgen-dependence in 1972, but progression to castration-resistant prostate cancer (CRPC) occurs within 2-3 years of initiation of ADT. CRPC, previously defined as hormone-refractory prostate cancer, is now understood to still be androgen dependent. Multiple mechanisms of resistance help contribute to the progression to castration resistant disease, and the androgen receptor (AR) remains an important driver in this progression. These mechanisms include AR amplification and hypersensitivity, AR mutations leading to promiscuity, mutations in coactivators/corepressors, androgen-independent AR activation, and intratumoral and alternative androgen production. More recently, identification of AR variants (ARVs) has been established as another mechanism of progression to CRPC. Docetaxel chemotherapy has historically been the first-line treatment for CRPC, but in recent years, newer agents have been introduced that target some of these mechanisms of resistance, thereby providing additional survival benefit. These include AR signaling inhibitors such as enzalutamide (Xtandi, ENZA, MDV-3100) and CYP17A1 inhibitors such as abiraterone acetate (Zytiga). Ultimately, these agents will also fail to suppress CRPC. While some of the mechanisms by which these agents fail are unique, many share similarities to the mechanisms contributing to CRPC progression. Understanding these mechanisms of resistance to ADT and currently approved CRPC treatments will help guide future research into targeted therapies. PMID- 26814154 TI - Use of an explicit rule decreases procrastination in university students. AB - The procrastination behavior of students from a small rural university was decreased by presenting them with a rule indicating that a sooner final due date for a writing assignment would be contingent on procrastination during earlier phases of the paper. A counterbalanced AB BA design was used to measure the effects of the rule-based treatment across 2 introductory psychology classes (N = 33). Overall, participants engaged in less procrastination, missed fewer deadlines, and produced higher quality writing in the treatment condition. PMID- 26814153 TI - Hyperuricemia and the risk for coronary heart disease morbidity and mortality a systematic review and dose-response meta-analysis. AB - Considerable controversy exists regarding the association between hyperuricemia and coronary heart disease (CHD). Therefore, we performed a systematic review and dose-response meta-analysis of prospective studies to examine the controversy. Prospective cohort studies with relative risks (RRs) and 95% confidence intervals (CIs) for CHD according to serum uric acid levels in adults were eligible. A random-effects model was used to compute the pooled risk estimate. The search yielded 29 prospective cohort studies (n = 958410 participants). Hyperuricemia was associated with increased risk of CHD morbidity (adjusted RR 1.13; 95% CI 1.05 to 1.21) and mortality (adjusted RR 1.27; 95% CI 1.16 to 1.39). For each increase of 1 mg/dl in uric acid level, the pooled multivariate RR of CHD mortality was 1.13 (95% CI 1.06 to 1.20). Dose-response analysis indicated that the combined RR of CHD mortality for an increase of 1 mg uric acid level per dl was 1.02 (95% CI 0.84 to 1.24) without heterogeneity among males (P = 0.879, I(2) = 0%) and 2.44 (95% CI 1.69 to 3.54) without heterogeneity among females (P = 0.526, I(2) = 0%). The increased risk of CHD associated with hyperuricemia was consistent across most subgroups. Hyperuricemia may increase the risk of CHD events, particularly CHD mortality in females. PMID- 26814156 TI - Phillip Frank Lewis 1919-2015. PMID- 26814157 TI - Raw beef bones as chewing items to reduce dental calculus in Beagle dogs. AB - OBJECTIVE: Evaluate the effect of raw bovine cortical bone (CB) (medullary bone cross-sectioned) and marrow or epiphyseal 'spongy' bone (SB) as chew items to reduce dental calculus in adult dogs. METHODS: Eight 3-year-old Beagle dogs were observed in two study periods. In the first study, the dogs each received a piece of bovine femur CB (122 +/- 17 g) daily and in the second study, a piece of bovine femur SB (235 +/- 27 g). The first study lasted 12 days and the second 20 days. Dental calculus was evaluated using image integration software. RESULTS: At the start of the studies, dental calculus covered 42.0% and 38.6% of the dental arcade areas, respectively. In study one, the chewing reduced the established dental calculus area to 27.1% (35.5% reduction) after 3 days and after 12 days the dental calculus covering was reduced to 12.3% (70.6% reduction). In study two, the dental calculus covered 16.8% (56.5% reduction) after 3 days, 7.1% (81.6% reduction) after 12 days and 4.7% (87.8% reduction) after 20 days. The CB remained largely intact after 24 h, but SB was reduced to smaller pieces and in some cases totally consumed after 24 h. No complications such as tooth fractures, pieces of bone stuck between teeth or intestinal obstructions were observed during the studies. CONCLUSIONS: Chewing raw bovine bones was an effective method of removing dental calculus in dogs. The SB bones removed dental calculus more efficiently in the short term. PMID- 26814158 TI - Dachshund bitch with severe uterine adhesions and intramural uterine foreign material as an incidental ovariohysterectomy finding. PMID- 26814159 TI - Effect of Manuka honey gel on the transforming growth factor beta1 and beta3 concentrations, bacterial counts and histomorphology of contaminated full thickness skin wounds in equine distal limbs. AB - OBJECTIVE: To investigate the effect of 66% Manuka honey gel on the concentrations of transforming growth factor (TGF)-beta1 and TGF-beta3, bacterial counts and histomorphology during healing of contaminated equine distal limb wounds. METHODS: In this experimental study of 10 Standardbred horses, five full thickness skin wounds (2 * 1.5 cm) were created on one metacarpus and six similar wounds were created on the contralateral metacarpus. Wounds were assigned to three groups: non-contaminated control wounds; contaminated control wounds; contaminated wounds treated daily with 1 mL Manuka honey gel topically for 10 days. For the contaminated wounds, faeces were applied for 24 h after wound creation. In five horses wounds were bandaged and in the other five horses wounds were left without a bandage. Biopsies were taken on days 1, 2, 7 and 10 after wounding to evaluate the effects of Manuka honey gel, wound contamination and bandaging on TGF-beta1 and TGF-beta3 concentrations, aerobic and anaerobic bacterial counts, and histomorphology. RESULTS: Manuka honey gel had no significant effect on TGF-beta1 and TGF-beta3 concentrations or wound bacterial counts. Manuka honey gel decreased wound inflammation (days 7, 10), increased angiogenesis (days 2, 7, 10), increased fibrosis and collagen organisation (day 7) and increased epithelial hyperplasia (days 7, 10). CONCLUSIONS: Treatment with Manuka honey gel resulted in a more organised granulation tissue bed early in wound repair, which may contribute to enhanced healing of equine distal limb wounds. PMID- 26814160 TI - Anthelmintic resistance in gastrointestinal nematodes of dairy cattle in the Macalister Irrigation District of Victoria. AB - OBJECTIVE: To report anthelmintic resistance in gastrointestinal nematode parasites of cattle on commercial dairy farms in the Macalister Irrigation District of Gippsland, Victoria. METHODS: Faecal egg count reduction tests (FECRTs) were used to assess anthelmintic resistance on 20 Macalister Irrigation District dairy farms between May 2013 and June 2014. All three currently available anthelmintic classes for cattle nematodes in Australia were tested. Faecal samples were collected 10-14 days post-treatment for individual faecal egg counts (FEC) and larval differentiation. The arithmetic mean FEC for each treatment group was compared with an untreated control post-treatment. Resistance was defined as <95% reduction in FEC, with a lower 95% confidence interval <90% when the mean FEC of the control group, differentiated by genus, was greater than 25 eggs/g. RESULTS: Anthelmintic resistance was present on all 20 dairy farms involved in this study. Resistance to doramectin in at least one species was detected on 15/20 (70%) farms, fenbendazole on 16/20 (80%) farms and levamisole on 5/20 (25%) farms. On three farms, resistance by Ostertagia ostertagi to all three anthelmintic classes was detected. CONCLUSION: This is the first report of anthelmintic-resistant O. ostertagi on Australian dairy farms. Resistance to all three available anthelmintic classes is of concern, given the high pathogenicity of this species. The study highlights the need for veterinarians and dairy farmers to be aware of the risks posed by anthelmintic resistance. PMID- 26814161 TI - Andrew Hansen 1945-2015. PMID- 26814164 TI - PC-SAFT Modeling of CO2 Solubilities in Deep Eutectic Solvents. AB - Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT), a physically based model that accounts for different molecular interactions explicitly, was applied to describe for the first time the phase behavior of deep eutectic solvents (DESs) with CO2 at temperatures from 298.15 to 318.15 K and pressures up to 2 MPa. DESs are mixtures of two solid compounds, a hydrogen bond donor (HBD) and a hydrogen bond acceptor (HBA), which form liquids upon mixing with melting points far below that of the individual compounds. In this work, the HBD is lactic acid and the HBAs are tetramethylammonium chloride, tetraethylammonium chloride, and tetrabutylammonium chloride. Two different modeling strategies were considered for the PC-SAFT modeling. In the first strategy, the so-called pseudo pure component approach, a DES was considered as a pseudo-pure compound, and its pure-component parameters were obtained by fitting to pure DES density data. In the second strategy, the so-called individual-component approach, a DES was considered to consist of two individual components (HBA and HBD), and the pure component parameters of the HBA and HBD were obtained by fitting to the density of aqueous solutions containing only the individual compounds of the DES. In order to model vapor-liquid equilibria (VLE) of DES + CO2 systems, binary interaction parameters were adjusted to experimental data from the literature and to new data measured in this work. It was concluded that the individual-component strategy allows quantitative prediction of the phase behavior of DES + CO2 systems containing those HBD:HBA molar ratios that were not used for k(ij) fitting. In contrast, applying the pseudo-pure component strategy required DES composition specific k(ij) parameters. PMID- 26814165 TI - Time Invariant Surface Roughness Evolution during Atmospheric Pressure Thin Film Depositions. AB - The evolution of thin film morphology during atmospheric pressure deposition has been studied utilizing Monte Carlo methods. Time invariant root-mean-squared roughness and local roughness morphology were both observed when employing a novel simulation parameter, modeling the effect of the experimental high pressure condition. This growth regime, where the surface roughness remains invariant after reaching a critical value, has not been classified by any existing universality class. An anti-shadowing growth mechanism responsible for this regime occurs when particles undergo binary collisions beneath the surface apexes. Hence, this mechanism is applicable when the mean free path of the depositing species is comparable to the amplitude of the surface features. Computationally this has been modeled by allowing particles to change direction at a specified height above the local film surface. This modification of the incoming flux trajectory consequently has a dramatic smoothening effect, and the resulting surfaces appear in agreement with recent experimental observations. PMID- 26814163 TI - CD45RA, a specific marker for leukaemia stem cell sub-populations in acute myeloid leukaemia. AB - Chemotherapy resistant leukaemic stem cells (LSC) are thought to be responsible for relapses after therapy in acute myeloid leukaemia (AML). Flow cytometry can discriminate CD34(+) CD38(-) LSC and normal haematopoietic stem cells (HSC) by using aberrant expression of markers and scatter properties. However, not all LSC can be identified using currently available markers, so new markers are needed. CD45RA is expressed on leukaemic cells in the majority of AML patients. We investigated the potency of CD45RA to specifically identify LSC and HSC and improve LSC quantification. Compared to our best other markers (CLL-1, also termed CLEC12A, CD33 and CD123), CD45RA was the most reliable marker. Patients with high percentages (>90%) of CD45RA on CD34(+) CD38(-) LSC have 1.69-fold higher scatter values compared to HSC (P < 0.001), indicating a more mature CD34(+) CD38(-) phenotype. Patients with low (<10%) or intermediate (10-90%) CD45RA expression on LSC showed no significant differences to HSC (1.12- and 1.15 fold higher, P = 0.31 and P = 0.44, respectively). CD45RA-positive LSC tended to represent more favourable cytogenetic/molecular markers. In conclusion, CD45RA contributes to more accurate LSC detection and is recommended for inclusion in stem cell tracking panels. CD45RA may contribute to define new LSC-specific therapies and to monitor effects of anti-LSC treatment. PMID- 26814166 TI - Precision Medicine: Genetic Repair of Retinitis Pigmentosa in Patient-Derived Stem Cells. AB - Induced pluripotent stem cells (iPSCs) generated from patient fibroblasts could potentially be used as a source of autologous cells for transplantation in retinal disease. Patient-derived iPSCs, however, would still harbor disease causing mutations. To generate healthy patient-derived cells, mutations might be repaired with new gene-editing technology based on the bacterial system of clustered regularly interspersed short palindromic repeats (CRISPR)/Cas9, thereby yielding grafts that require no patient immunosuppression. We tested whether CRISPR/Cas9 could be used in patient-specific iPSCs to precisely repair an RPGR point mutation that causes X-linked retinitis pigmentosa (XLRP). Fibroblasts cultured from a skin-punch biopsy of an XLRP patient were transduced to produce iPSCs carrying the patient's c.3070G > T mutation. The iPSCs were transduced with CRISPR guide RNAs, Cas9 endonuclease, and a donor homology template. Despite the gene's repetitive and GC-rich sequences, 13% of RPGR gene copies showed mutation correction and conversion to the wild-type allele. This is the first report using CRISPR to correct a pathogenic mutation in iPSCs derived from a patient with photoreceptor degeneration. This important proof-of-concept finding supports the development of personalized iPSC-based transplantation therapies for retinal disease. PMID- 26814167 TI - Retrospective study of the incidence and patterns of arterial and venous thrombosis in Chinese versus African American patients with multiple myeloma. PMID- 26814168 TI - Fitness costs of increased cataract frequency and cumulative radiation dose in natural mammalian populations from Chernobyl. AB - A cataract is a clouding of the lens that reduces light transmission to the retina, and it decreases the visual acuity of the bearer. The prevalence of cataracts in natural populations of mammals, and their potential ecological significance, is poorly known. Cataracts have been reported to arise from high levels of oxidative stress and a major cause of oxidative stress is ionizing radiation. We investigated whether elevated frequencies of cataracts are found in eyes of bank voles Myodes glareolus collected from natural populations in areas with varying levels of background radiation in Chernobyl. We found high frequencies of cataracts in voles collected from different areas in Chernobyl. The frequency of cataracts was positively correlated with age, and in females also with the accumulated radiation dose. Furthermore, the number of offspring in female voles was negatively correlated with cataract severity. The results suggest that cataracts primarily develop as a function of ionizing background radiation, most likely as a plastic response to high levels of oxidative stress. It is therefore possible that the elevated levels of background radiation in Chernobyl affect the ecology and fitness of local mammals both directly through, for instance, reduced fertility and indirectly, through increased cataractogenesis. PMID- 26814169 TI - Use of machine learning approaches for novel drug discovery. AB - INTRODUCTION: The use of computational tools in the early stages of drug development has increased in recent decades. Machine learning (ML) approaches have been of special interest, since they can be applied in several steps of the drug discovery methodology, such as prediction of target structure, prediction of biological activity of new ligands through model construction, discovery or optimization of hits, and construction of models that predict the pharmacokinetic and toxicological (ADMET) profile of compounds. AREAS COVERED: This article presents an overview on some applications of ML techniques in drug design. These techniques can be employed in ligand-based drug design (LBDD) and structure-based drug design (SBDD) studies, such as similarity searches, construction of classification and/or prediction models of biological activity, prediction of secondary structures and binding sites docking and virtual screening. EXPERT OPINION: Successful cases have been reported in the literature, demonstrating the efficiency of ML techniques combined with traditional approaches to study medicinal chemistry problems. Some ML techniques used in drug design are: support vector machine, random forest, decision trees and artificial neural networks. Currently, an important application of ML techniques is related to the calculation of scoring functions used in docking and virtual screening assays from a consensus, combining traditional and ML techniques in order to improve the prediction of binding sites and docking solutions. PMID- 26814170 TI - A Tunable Protein Piston That Breaks Membranes to Release Encapsulated Cargo. AB - Movement of molecules across membranes in response to a stimulus is a key component of cellular programming. Here, we characterize and manipulate the response of a protein-based piston capable of puncturing membranes in a pH dependent manner. Our protein actuator consists of modified R bodies found in a bacterial endosymbiont of paramecium. We express and purify R bodies from in E. coli; these pistons undergo multiple rounds of rapid extension and retraction. We developed a high throughput screen for mutants with altered pH sensitivity for tuning of the extension process. We show that the R bodies are capable of acting as synthetic pH-dependent pistons that can puncture E. coli membranes to release the trapped content. As such, these protein machines present a novel way to selectively rupture membrane compartments and will be important for programming cellular compartmentalization. PMID- 26814172 TI - Declaration. PMID- 26814171 TI - How beta3 -adrenoceptor-selective is mirabegron? PMID- 26814173 TI - Current Investigational Drugs for the Treatment of Attention Deficit/Hyperactivity Disorder. AB - INTRODUCTION: Symptoms of attention-deficit/hyperactivity disorder (ADHD) were first described more than 100 years ago. It is a common neurobehavioral disorder that begins in childhood and often persists into adulthood. Treatment for ADHD has been available since Bradley first prescribed amphetamines for hyperkinetic boys more than 70 years ago. Although multiple effective medications for the treatment of ADHD are on the market, all have limitations. Stimulants are controlled substances and may not be effective or tolerable for all patients. The non-stimulants are not as effective as stimulants and have their own side effect profiles. AREAS COVERED: In this review, the limitations of currently available medications including methylphenidates, amphetamines, atomoxetine, extended release guanfacine and extended-release clonidine are considered and drugs in development for the treatment of ADHD are examined. Although the main focus is on phase I and II trials, drugs which may soon be marketed are also discussed. EXPERT OPINION: Multiple drugs are currently in development, with several targeting novel receptors originally identified using animal models. Since ADHD appears to be complex disorder associated with multiple genes, these models have often not predicted effectiveness in humans. Until there is a better understanding of the genetics of ADHD, drug development will remain challenging. PMID- 26814174 TI - Eye movement disorders are an early manifestation of CACNA1A mutations in children. AB - AIM: The alpha-1 isoform of the calcium channel gene is expressed abundantly in neuronal tissue, especially within the cerebellum. Mutations in this gene may manifest with hemiplegic migraine, spinocerebellar ataxia type 6 (SCA6) and episodic ataxia type 2 (EA2) in adults. There are reports of children with CACAN1A mutations presenting with paroxysmal tonic upgaze, abnormal saccades and congenital nystagmus as well as severe forms of hemiplegic migraine. The aim of this study was to review the clinical presentation and subsequent course of all children with a CACNA1A mutation who presented to a tertiary children's hospital. METHOD: We reviewed retrospectively nine children with a proven CACNA1A mutation who presented to the Children's Hospital at Westmead between 2005-2015. The initial and subsequent clinical presentation, radiological features and molecular genetic profile of each child was reviewed. RESULTS: Nine children presented to out institute over a 10 year period; six were female and three male. The median age of presentation was 1.2 years. Eye movement disorders were the presenting feature in eight children. Three of these children later presented with severe hemiplegic migraine episodes often requiring ICU care. Affected children also had developmental delay and developed classical hemiplegic migraine, episodic ataxia and seizures. Calcium channel blockers were used with some efficacy in preventing severe HM episodes. INTERPRETATION: Eye movement disorders are an early manifestation of CACNA1A mutations in children. Improved recognition of the CACNA1A phenotype in childhood is important for early diagnosis, counselling and appropriate emergency management. There is some early evidence that calcium channel blockers may be an effective prophylactic agent for the severe hemiplegic migraine episodes. PMID- 26814176 TI - The Adenovirus E4-ORF3 Protein Stimulates SUMOylation of General Transcription Factor TFII-I to Direct Proteasomal Degradation. AB - Modulation of host cell transcription, translation, and posttranslational modification processes is critical for the ability of many viruses to replicate efficiently within host cells. The human adenovirus (Ad) early region 4 open reading frame 3 (E4-ORF3) protein forms unique inclusions throughout the nuclei of infected cells and inhibits the antiviral Mre11-Rad50-Nbs1 DNA repair complex through relocalization. E4-ORF3 also induces SUMOylation of Mre11 and Nbs1. We recently identified additional cellular targets of E4-ORF3 and found that E4-ORF3 stimulates ubiquitin-like modification of 41 cellular proteins involved in a wide variety of processes. Among the proteins most abundantly modified in an E4-ORF3 dependent manner was the general transcription factor II-I (TFII-I). Analysis of Ad-infected cells revealed that E4-ORF3 induces TFII-I relocalization and SUMOylation early during infection. In the present study, we explored the relationship between E4-ORF3 and TFII-I. We found that Ad infection or ectopic E4 ORF3 expression leads to SUMOylation of TFII-I that precedes a rapid decline in TFII-I protein levels. We also show that E4-ORF3 is required for ubiquitination of TFII-I and subsequent proteasomal degradation. This is the first evidence that E4-ORF3 regulates ubiquitination. Interestingly, we found that E4-ORF3 modulation of TFII-I occurs in diverse cell types but only E4-ORF3 of Ad species C regulates TFII-I, providing critical insight into the mechanism by which E4-ORF3 targets TFII-I. Finally, we show that E4-ORF3 stimulates the activity of a TFII-I repressed viral promoter during infection. Our results characterize a novel mechanism of TFII-I regulation by Ad and highlight how a viral protein can modulate a critical cellular transcription factor during infection. IMPORTANCE: Adenovirus has evolved a number of mechanisms to target host signaling pathways in order to optimize the cellular environment during infection. E4-ORF3 is a small viral protein made early during infection, and it is critical for inactivating host antiviral responses. In addition to its ability to capture and reorganize cellular proteins, E4-ORF3 also regulates posttranslational modifications of target proteins, but little is known about the functional consequences of these modifications. We recently identified TFII-I as a novel target of E4-ORF3 that is relocalized into dynamic E4-ORF3 nuclear structures and subjected to E4-ORF3-mediated SUMO modification. Here, we show that TFII-I is targeted by E4-ORF3 for ubiquitination and proteasomal degradation and that E4 ORF3 stimulates gene expression from a TFII-I-repressed viral promoter. Our findings suggest that the specific targeting of TFII-I by E4-ORF3 is a mechanism to inactivate its antiviral properties. These studies provide further insight into how E4-ORF3 functions to counteract host antiviral responses. PMID- 26814175 TI - Human Mesenchymal Stem Cells of Diverse Origins Support Persistent Infection with Kaposi's Sarcoma-Associated Herpesvirus and Manifest Distinct Angiogenic, Invasive, and Transforming Phenotypes. AB - Kaposi's sarcoma (KS), a highly angiogenic and invasive tumor often involving different organ sites, including the oral cavity, is caused by infection with Kaposi's sarcoma-associated herpesvirus (KSHV). Diverse cell markers have been identified on KS tumor cells, but their origin remains an enigma. We previously showed that KSHV could efficiently infect, transform, and reprogram rat primary mesenchymal stem cells (MSCs) into KS-like tumor cells. In this study, we showed that human primary MSCs derived from diverse organs, including bone marrow (MSCbm), adipose tissue (MSCa), dental pulp, gingiva tissue (GMSC), and exfoliated deciduous teeth, were permissive to KSHV infection. We successfully established long-term cultures of KSHV-infected MSCa, MSCbm, and GMSC (LTC KMSCs). While LTC-KMSCs had lower proliferation rates than the uninfected cells, they expressed mixtures of KS markers and displayed differential angiogenic, invasive, and transforming phenotypes. Genetic analysis identified KSHV-derived microRNAs that mediated KSHV-induced angiogenic activity by activating the AKT pathway. These results indicated that human MSCs could be the KSHV target cells in vivo and established valid models for delineating the mechanism of KSHV infection, replication, and malignant transformation in biologically relevant cell types. IMPORTANCE: Kaposi's sarcoma is the most common cancer in AIDS patients. While KSHV infection is required for the development of Kaposi's sarcoma, the origin of KSHV target cells remains unclear. We show that KSHV can efficiently infect human primary mesenchymal stem cells of diverse origins and reprogram them to acquire various degrees of Kaposi's sarcoma-like cell makers and angiogenic, invasive, and transforming phenotypes. These results indicate that human mesenchymal stem cells might be the KSHV target cells and establish models for delineating the mechanism of KSHV-induced malignant transformation. PMID- 26814177 TI - Ssn6 Defines a New Level of Regulation of White-Opaque Switching in Candida albicans and Is Required For the Stochasticity of the Switch. AB - The human commensal and opportunistic pathogen Candida albicans can switch between two distinct, heritable cell types, named "white" and "opaque," which differ in morphology, mating abilities, and metabolic preferences and in their interactions with the host immune system. Previous studies revealed a highly interconnected group of transcriptional regulators that control switching between the two cell types. Here, we identify Ssn6, the C. albicans functional homolog of the Saccharomyces cerevisiae transcriptional corepressor Cyc8, as a new regulator of white-opaque switching. In A: or alpha mating type strains, deletion of SSN6 results in mass switching from the white to the opaque cell type. Transcriptional profiling of ssn6 deletion mutant strains reveals that Ssn6 represses part of the opaque cell transcriptional program in white cells and the majority of the white cell transcriptional program in opaque cells. Genome-wide chromatin immunoprecipitation experiments demonstrate that Ssn6 is tightly integrated into the opaque cell regulatory circuit and that the positions to which it is bound across the genome strongly overlap those bound by Wor1 and Wor2, previously identified regulators of white-opaque switching. This work reveals the next layer in the white-opaque transcriptional circuitry by integrating a transcriptional regulator that does not bind DNA directly but instead associates with specific combinations of DNA-bound transcriptional regulators. IMPORTANCE: The most common fungal pathogen of humans, C. albicans, undergoes several distinct morphological transitions during interactions with its host. One such transition, between cell types named "white" and "opaque," is regulated in an epigenetic manner, in the sense that changes in gene expression are heritably maintained without any modification of the primary genomic DNA sequence. Prior studies revealed a highly interconnected network of sequence-specific DNA-binding proteins that control this switch. We report the identification of Ssn6, which defines an additional layer of transcriptional regulation that is critical for this heritable switch. Ssn6 is necessary to maintain the white cell type and to properly express the opaque cell transcriptional program. Ssn6 does not bind DNA directly but rather associates with specific combinations of DNA-bound transcriptional regulators to control the switch. This work is significant because it reveals a new level of regulation of an important epigenetic switch in the predominant fungal pathogen of humans. PMID- 26814178 TI - Characterization of a Multipeptide Lantibiotic Locus in Streptococcus pneumoniae. AB - Bacterial communities are established through a combination of cooperative and antagonistic interactions between the inhabitants. Competitive interactions often involve the production of antimicrobial substances, including bacteriocins, which are small antimicrobial peptides that target other community members. Despite the nearly ubiquitous presence of bacteriocin-encoding loci, inhibitory activity has been attributed to only a small fraction of gene clusters. In this study, we characterized a novel locus (the pld locus) in the pathogen Streptococcus pneumoniae that drives the production of a bacteriocin called pneumolancidin, which has broad antimicrobial activity. The locus encodes an unusual tandem array of four inhibitory peptides, three of which are absolutely required for antibacterial activity. The three peptide sequences are similar but appear to play distinct roles in regulation and inhibition. A modification enzyme typically found in loci encoding a class of highly modified bacteriocins called lantibiotics was required for inhibitory activity. The production of pneumolancidin is controlled by a two-component regulatory system that is activated by the accumulation of modified peptides. The locus is located on a mobile element that has been found in many pneumococcal lineages, although not all elements carry the pld genes. Intriguingly, a minimal region containing only the genes required for pneumolancidin immunity was found in several Streptococcus mitis strains. The pneumolancidin-producing strain can inhibit nearly all pneumococci tested to date and provided a competitive advantage in vivo. These peptides not only represent a unique strategy for bacterial competition but also are an important resource to guide the development of new antimicrobials. IMPORTANCE: Successful colonization of a polymicrobial host surface is a prerequisite for the subsequent development of disease for many bacterial pathogens. Bacterial factors that directly inhibit the growth of neighbors may provide an advantage during colonization if the inhibition of competitors outweighs the energy for production. In this work, we found that production of a potent antimicrobial called pneumolancidin conferred a competitive advantage to the pathogen Streptococcus pneumoniae. S. pneumoniae secreting pneumolancidin inhibits a wide array of Gram-positive organisms, including all but one tested pneumococcal strain. The pneumolancidin genetic locus is of particular interest because it encodes three similar modified peptides (lantibiotics), each of which has a distinct role in the function of the locus. Lantibiotics represent a relatively untapped resource for the development of clinically useful antibiotics which are desperately needed. The broad inhibitory activity of pneumolancidin makes it an ideal candidate for further characterization and development. PMID- 26814180 TI - Kisameet Clay Exhibits Potent Antibacterial Activity against the ESKAPE Pathogens. AB - The ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens cause an increasing number of nosocomial infections worldwide since they escape the inhibitory effect of the available antibiotics and the immune response. Here, we report the broad-spectrum and potent antibacterial activity of Kisameet clay, a natural clay mineral from British Columbia, Canada, against a group of multidrug-resistant ESKAPE strains. The results suggest that this natural clay might be developed as a therapeutic option for the treatment of serious infections caused by these important pathogens. IMPORTANCE: More than 50 years of misuse and overuse of antibiotics has led to a plague of antibiotic resistance that threatens to reduce the efficacy of antimicrobial agents available for the treatment of infections due to resistant organisms. The main threat is nosocomial infections in which certain pathogens, notably the ESKAPE organisms, are essentially untreatable and contribute to increasing mortality and morbidity in surgical wards. The pipeline of novel antimicrobials in the pharmaceutical industry is essentially empty. Thus, there is a great need to seek for new sources for the treatment of recalcitrant infectious diseases. We describe experiments that demonstrate the efficacy of a "natural" medicine, Kisameet clay, against all of the ESKAPE strains. We suggest that this material is worthy of clinical investigation for the treatment of infections due to multidrug-resistant organisms. PMID- 26814179 TI - The Atomic Structure of the Phage Tuc2009 Baseplate Tripod Suggests that Host Recognition Involves Two Different Carbohydrate Binding Modules. AB - The Gram-positive bacterium Lactococcus lactis, used for the production of cheeses and other fermented dairy products, falls victim frequently to fortuitous infection by tailed phages. The accompanying risk of dairy fermentation failures in industrial facilities has prompted in-depth investigations of these phages. Lactococcal phage Tuc2009 possesses extensive genomic homology to phage TP901-1. However, striking differences in the baseplate-encoding genes stimulated our interest in solving the structure of this host's adhesion device. We report here the X-ray structures of phage Tuc2009 receptor binding protein (RBP) and of a "tripod" assembly of three baseplate components, BppU, BppA, and BppL (the RBP). These structures made it possible to generate a realistic atomic model of the complete Tuc2009 baseplate that consists of an 84-protein complex: 18 BppU, 12 BppA, and 54 BppL proteins. The RBP head domain possesses a different fold than those of phages p2, TP901-1, and 1358, while the so-called "stem" and "neck" domains share structural features with their equivalents in phage TP901-1. The BppA module interacts strongly with the BppU N-terminal domain. Unlike other characterized lactococcal phages, Tuc2009 baseplate harbors two different carbohydrate recognition sites: one in the bona fide RBP head domain and the other in BppA. These findings represent a major step forward in deciphering the molecular mechanism by which Tuc2009 recognizes its saccharidic receptor(s) on its host. IMPORTANCE: Understanding how siphophages infect Lactococcus lactis is of commercial importance as they cause milk fermentation failures in the dairy industry. In addition, such knowledge is crucial in a general sense in order to understand how viruses recognize their host through protein-glycan interactions. We report here the lactococcal phage Tuc2009 receptor binding protein (RBP) structure as well as that of its baseplate. The RBP head domain has a different fold than those of phages p2, TP901-1, and 1358, while the so-called "stem" and "neck" share the fold characteristics also found in the equivalent baseplate proteins of phage TP901-1. The baseplate structure contains, in contrast to other characterized lactococcal phages, two different carbohydrate binding modules that may bind different motifs of the host's surface polysaccharide. PMID- 26814181 TI - Helicobacter pylori Diversity and Gastric Cancer Risk. AB - Gastric cancer is a leading cause of cancer-related death worldwide. Helicobacter pylori infection is the strongest known risk factor for this malignancy. An important goal is to identify H. pylori-infected persons at high risk for gastric cancer, so that these individuals can be targeted for therapeutic intervention. H. pylori exhibits a high level of intraspecies genetic diversity, and over the past two decades, many studies have endeavored to identify strain-specific features of H. pylori that are linked to development of gastric cancer. One of the most prominent differences among H. pylori strains is the presence or absence of a 40-kb chromosomal region known as the cag pathogenicity island (PAI). Current evidence suggests that the risk of gastric cancer is very low among persons harboring H. pylori strains that lack the cag PAI. Among persons harboring strains that contain the cag PAI, the risk of gastric cancer is shaped by a complex interplay among multiple strain-specific bacterial factors as well as host factors. This review discusses the strain-specific properties of H. pylori that correlate with increased gastric cancer risk, focusing in particular on secreted proteins and surface-exposed proteins, and describes evidence from cell culture and animal models linking these factors to gastric cancer pathogenesis. Strain-specific features of H. pylori that may account for geographic variation in gastric cancer incidence are also discussed. PMID- 26814183 TI - Identification and Characterization of the Novel Subunit CcoM in the cbb33Cytochrome c Oxidase from Pseudomonas stutzeri ZoBell. AB - Cytochrome c oxidases (CcOs), members of the heme-copper containing oxidase (HCO) superfamily, are the terminal enzymes of aerobic respiratory chains. The cbb3 type cytochrome c oxidases (cbb3-CcO) form the C-family and have only the central catalytic subunit in common with the A- and B-family HCOs. In Pseudomonas stutzeri, two cbb3 operons are organized in a tandem repeat. The atomic structure of the first cbb3 isoform (Cbb3-1) was determined at 3.2 A resolution in 2010 (S. Buschmann, E. Warkentin, H. Xie, J. D. Langer, U. Ermler, and H. Michel, Science 329:327-330, 2010, http://dx.doi.org/10.1126/science.1187303). Unexpectedly, the electron density map of Cbb3-1 revealed the presence of an additional transmembrane helix (TMH) which could not be assigned to any known protein. We now identified this TMH as the previously uncharacterized protein PstZoBell_05036, using a customized matrix-assisted laser desorption ionization (MALDI)-tandem mass spectrometry setup. The amino acid sequence matches the electron density of the unassigned TMH. Consequently, the protein was renamed CcoM. In order to identify the function of this new subunit in the cbb3 complex, we generated and analyzed a CcoM knockout strain. The results of the biochemical and biophysical characterization indicate that CcoM may be involved in CcO complex assembly or stabilization. In addition, we found that CcoM plays a role in anaerobic respiration, as the DeltaCcoM strain displayed altered growth rates under anaerobic denitrifying conditions. IMPORTANCE: The respiratory chain has recently moved into the focus for drug development against prokaryotic human pathogens, in particular, for multiresistant strains (P. Murima, J. D. McKinney, and K. Pethe, Chem Biol 21:1423-1432, 2014, http://dx.doi.org/10.1016/j.chembiol.2014.08.020). cbb3-CcO is an essential enzyme for many different pathogenic bacterial species, e.g., Helicobacter pylori, Vibrio cholerae, and Pseudomonas aeruginosa, and represents a promising drug target. In order to develop compounds targeting these proteins, a detailed understanding of the molecular architecture and function is required. Here we identified and characterized a novel subunit, CcoM, in the cbb3-CcO complex and thereby completed the crystal structure of the Cbb3 oxidase from Pseudomonas stutzeri, a bacterium closely related to the human pathogen Pseudomonas aeruginosa. PMID- 26814185 TI - Update on the use of abdominal and thoracic endografts for treating aortic aneurysms. AB - Endovascular abdominal and thoracic aneurysm repair has heralded a paradigm shift in the management of abdominal and thoracic aortic aneurysms. Randomized controlled trials have suggested superior short-term and equivalent long-term outcomes of endovascular repair compared with open surgery. Existing endografts have undergone several modifications to meet anatomic challenges and improve patient results. In the past, endovascular repair has been limited to infrarenal abdominal aortic aneurysms and isolated thoracic aortic aneurysms. The advent of fenestrated and branched endografts have made endovascular repair of thoracoabdominal and juxtarenal aneurysms possible. Continued evolution of endograft technology will maximize the benefit and minimize complications in patients with a range of aneurysmal disease. PMID- 26814182 TI - Fighting the Monster: Applying the Host Damage Framework to Human Central Nervous System Infections. AB - The host damage-response framework states that microbial pathogenesis is a product of microbial virulence factors and collateral damage from host immune responses. Immune-mediated host damage is particularly important within the size restricted central nervous system (CNS), where immune responses may exacerbate cerebral edema and neurological damage, leading to coma and death. In this review, we compare human host and therapeutic responses in representative nonviral generalized CNS infections that induce archetypal host damage responses: cryptococcal menigoencephalitis and tuberculous meningitis in HIV-infected and non-HIV-infected patients, pneumococcal meningitis, and cerebral malaria. Consideration of the underlying patterns of host responses provides critical insights into host damage and may suggest tailored adjunctive therapeutics to improve disease outcome. PMID- 26814184 TI - Escherichia coli Quorum-Sensing EDF, A Peptide Generated by Novel Multiple Distinct Mechanisms and Regulated by trans-Translation. AB - Eshcerichia coli mazEF is a stress-induced toxin-antitoxin module mediating cell death and requiring a quorum-sensing (QS) extracellular death factor (EDF), the pentapeptide NNWNN. Here we uncovered several distinct molecular mechanisms involved in its generation from the zwf mRNA encoding glucose-6-phosphate dehydrogenase. In particular, we show that, under stress conditions, the endoribonuclease MazF cleaves specific ACA sites, thereby generating a leaderless zwf mRNA which is truncated 30 codons after the EDF-encoding region. Since the nascent ribosome peptide exit tunnel can accommodate up to 40 amino acids, this arrangement allows the localization of the EDF residues inside the tunnel when the ribosome is stalled at the truncation site. Moreover, ribosome stalling activates the trans-translation system, which provides a means for the involvement of ClpPX in EDF generation. Furthermore, the trans-translation is described as a regulatory system that attenuated the generation of EDF, leading to low levels of EDF in the single cell. Therefore, the threshold EDF molecule concentration required is achieved only by the whole population, as expected for QS. IMPORTANCE: Bacteria communicate with one another via quorum-sensing (QS) signal molecules. QS provides a mechanism for bacteria to monitor each other's presence and to modulate gene expression in response to population density. Previously, we added E. coli pentapeptide EDF to this list of QS molecules. We showed that, under stress conditions, the induced MazF, an endoribonuclease cleaving at ACA sites, generates EDF from zwf. Here we studied the mechanism of EDF generation and asked whether it is related to EDF density dependency. We illustrated that, under stress conditions, multiple distinct complex mechanisms are involved in EDF generation. This includes formation of leaderless truncated zwf mRNA by MazF, configuration of a length corresponding to the nascent ribosome peptide exit tunnel, rescue performed by the trans-translation system, and cleavage by ClpPX protease. trans-Translation is described as a regulatory system attenuating EDF generation and leading to low levels of EDF in the single cell, as expected for QS. PMID- 26814186 TI - Towards Understanding Male Infertility After Spinal Cord Injury Using Quantitative Proteomics. AB - The study of male infertility after spinal cord injury (SCI) has enhanced the understanding of seminal plasma (SP) as an important regulator of spermatozoa function. However, the most important factors leading to the diminished sperm motility and viability observed in semen of men with SCI remained unknown. Thus, to explore SP related molecular mechanisms underlying infertility after SCI, we used mass spectrometry-based quantitative proteomics to compare SP retrieved from SCI patients to normal controls. As a result, we present an in-depth characterization of the human SP proteome, identifying ~2,800 individual proteins, and describe, in detail, the differential proteome observed in SCI. Our analysis demonstrates that a hyper-activation of the immune system may influence some seminal processes, which likely are not triggered by microbial infection. Moreover, we show evidence of an important prostate gland functional failure,i.e.diminished abundance of metabolic enzymes related to ATP turnover and those secreted via prostasomes. Further we identify the main outcome related to this fact and that it is intrinsically linked to the low sperm motility in SCI. Together, our data highlights the molecular pathways hindering fertility in SCI and shed new light on other causes of male infertility. PMID- 26814188 TI - Reshaping the Chromatin and Epigenetic Landscapes with Quantitative Mass Spectrometry. PMID- 26814187 TI - Simultaneous Metabolite, Protein, Lipid Extraction (SIMPLEX): A Combinatorial Multimolecular Omics Approach for Systems Biology. AB - Interconnected molecular networks are at the heart of signaling pathways that mediate adaptive plasticity of eukaryotic cells. To gain deeper insights into the underlying molecular mechanisms, a comprehensive and representative analysis demands a deep and parallel coverage of a broad spectrum of molecular species. Therefore, we introduce a simultaneous metabolite, protein, lipid extraction (SIMPLEX) procedure, a novel strategy for the quantitative investigation of lipids, metabolites, and proteins. Compared with unimolecular workflows, SIMPLEX offers a fundamental turn in study design since multiple molecular classes can be accessed in parallel from one sample with equal efficiency and reproducibility. Application of this method in mass-spectrometry-based workflows allowed the simultaneous quantification of 360 lipids, 75 metabolites, and 3327 proteins from 10(6)cells. The versatility of this method is shown in a model system for adipogenesis- peroxisomal proliferator-activated receptor gamma (PPARG) signaling in mesenchymal stem cells-where we utilized SIMPLEX to explore cross-talk within and between all three molecular classes and identified novel potential molecular entry points for interventions, indicating that SIMPLEX provides a superior strategy compared with conventional workflows. PMID- 26814190 TI - Mapping the Quebec dental workforce: ranking rural oral health disparities. AB - INTRODUCTION: Ensuring access to oral health services is crucial for improving the oral health of rural and remote populations. A logical step towards addressing oral health disparities and underutilization of services in rural areas is to ensure the availability of the dental workforce. Geographical information systems are valuable in examining workforce dispersion patterns and identifying priority areas requiring administrative and policy attention. The objective of this study was to examine and map the distribution patterns of the dental workforce in Quebec, Canada. METHODS: Utilizing the membership directory of Quebec Professional Orders (2009-2010), data on practice locations, practice types and license issue date for all active members of the Quebec dental workforce were obtained. This was followed by reverse geocoding of the geographic coordinates using a global positioning system visualizer to reveal textual locations. These locations were classified according to various degrees of rurality as defined by the 2006 Census Metropolitan Area and Census Agglomeration Influenced Zone typology, developed by Statistics Canada. Cartography layers were extracted from a geospatial database provided by Canada Natural Resources using ArcGIS 9.3. Descriptive and bivariate analyses were performed using SPSS v17 for Windows. RESULTS: Data analysis revealed statistically significant differences in the distribution of dental professionals in rural and urban areas (urban 59.4+/ 19.4/100 000 vs rural 39.9+/-17.6/100 000; p<0.001). Approximately 90.3% of the dental workforce was located in urban zones, 1.3% in the zones strongly influenced by metropolitan area, 4.9% in the moderately influenced zones, while only 0.3% of the dental workforce was located in non-metropolitan-influenced zones. Urban zones such as Montreal, Quebec and Sherbrooke had the highest workforce availability (4-6 dentists for every 5000 inhabitants). Of a total of 447 specialist dentists in Quebec, only five were located in rural areas. CONCLUSIONS: This study concludes that there is a strong relationship between the degree of urbanization and the highest concentration of dental professionals. In addition, there is a lack of dental workforce availability, particularly specialists in rural Quebec. Further research is needed to examine and evaluate to what degree these distribution patterns might contribute to oral health outcomes of the rural population. PMID- 26814189 TI - Human Lineage-Specific Transcriptional Regulation through GA-Binding Protein Transcription Factor Alpha (GABPa). AB - A substantial fraction of phenotypic differences between closely related species are likely caused by differences in gene regulation. While this has already been postulated over 30 years ago, only few examples of evolutionary changes in gene regulation have been verified. Here, we identified and investigated binding sites of the transcription factor GA-binding protein alpha (GABPa) aiming to discover cis-regulatory adaptations on the human lineage. By performing chromatin immunoprecipitation-sequencing experiments in a human cell line, we found 11,619 putative GABPa binding sites. Through sequence comparisons of the human GABPa binding regions with orthologous sequences from 34 mammals, we identified substitutions that have resulted in 224 putative human-specific GABPa binding sites. To experimentally assess the transcriptional impact of those substitutions, we selected four promoters for promoter-reporter gene assays using human and African green monkey cells. We compared the activities of wild-type promoters to mutated forms, where we have introduced one or more substitutions to mimic the ancestral state devoid of the GABPa consensus binding sequence. Similarly, we introduced the human-specific substitutions into chimpanzee and macaque promoter backgrounds. Our results demonstrate that the identified substitutions are functional, both in human and nonhuman promoters. In addition, we performed GABPa knock-down experiments and found 1,215 genes as strong candidates for primary targets. Further analyses of our data sets link GABPa to cognitive disorders, diabetes, KRAB zinc finger (KRAB-ZNF), and human-specific genes. Thus, we propose that differences in GABPa binding sites played important roles in the evolution of human-specific phenotypes. PMID- 26814191 TI - Photostability enhancement of the pentacene derivative having two nitronyl nitroxide radical substituents. AB - Pentacene derivatives possessing nitronyl nitroxide radical substituents (1a and 1b) were synthesized, and their photochemical properties were evaluated. 1a with two radical substituents showed a remarkable enhancement of photostability compared with pentacene, 6,13-bis(triisopropylsilylethynyl)pentacene and the monoradical, 1b. This is understood due to the presence of the multiple deactivation pathways in the photoexcited states. PMID- 26814192 TI - Continuous cell lines from the Muscovy duck as potential replacement for primary cells in the production of avian vaccines. AB - Veterinary vaccines contribute to food security, interrupt zoonotic transmissions, and help to maintain overall health in livestock. Although vaccines are usually cost-effective, their adoption depends on a multitude of factors. Because poultry vaccines are usually given to birds with a short life span, very low production cost per dose is one important challenge. Other hurdles are to ensure a consistent and reliable supply of very large number of doses, and to have flexible production processes to accommodate a range of different pathogens and dosage requirements. Most poultry vaccines are currently being produced on primary avian cells derived from chicken or waterfowl embryos. This production system is associated with high costs, logistic complexities, rigid intervals between harvest and production, and supply limitations. We investigated whether the continuous cell lines Cairina retina and CR.pIX may provide a substrate independent of primary cell cultures or embryonated eggs. Viruses examined for replication in these cell lines are strains associated with, or contained in vaccines against egg drop syndrome, Marek's disease, Newcastle disease, avian influenza, infectious bursal disease and Derzsy's disease. Each of the tested viruses required the development of unique conditions for replication that are described here and can be used to generate material for in vivo efficacy studies and to accelerate transfer of the processes to larger production volumes. PMID- 26814193 TI - Orthogonal intercellular signaling for programmed spatial behavior. AB - Bidirectional intercellular signaling is an essential feature of multicellular organisms, and the engineering of complex biological systems will require multiple pathways for intercellular signaling with minimal crosstalk. Natural quorum-sensing systems provide components for cell communication, but their use is often constrained by signal crosstalk. We have established new orthogonal systems for cell-cell communication using acyl homoserine lactone signaling systems. Quantitative measurements in contexts of differing receiver protein expression allowed us to separate different types of crosstalk between 3-oxo-C6- and 3-oxo-C12-homoserine lactones, cognate receiver proteins, and DNA promoters. Mutating promoter sequences minimized interactions with heterologous receiver proteins. We used experimental data to parameterize a computational model for signal crosstalk and to estimate the effect of receiver protein levels on signal crosstalk. We used this model to predict optimal expression levels for receiver proteins, to create an effective two-channel cell communication device. Establishment of a novel spatial assay allowed measurement of interactions between geometrically constrained cell populations via these diffusible signals. We built relay devices capable of long-range signal propagation mediated by cycles of signal induction, communication and response by discrete cell populations. This work demonstrates the ability to systematically reduce crosstalk within intercellular signaling systems and to use these systems to engineer complex spatiotemporal patterning in cell populations. PMID- 26814194 TI - Low-Cost Air Quality Monitoring Methods to Assess Compliance With Smoke-Free Regulations: A Multi-Center Study in Six Low- and Middle-Income Countries. AB - INTRODUCTION: Many low- and middle-income countries (LMICs) have enacted legislation banning smoking in public places, yet enforcement remains challenging. The aim of this study was to assess the feasibility of using a validated low-cost methodology (the Dylos DC1700) to provide objective evidence of smoke-free (SF) law compliance in hospitality venues in urban LMIC settings, where outdoor air pollution levels are generally high. METHODS: Teams measured indoor fine particulate matter (PM2.5) concentrations and systematically observed smoking behavior and SF signage in a convenience sample of hospitality venues (bars, restaurants, cafes, and hotels) covered by existing SF legislation in Mexico, Pakistan, Indonesia, Chad, Bangladesh, and India. Outdoor air PM2.5 was also measured on each sampling day. RESULTS: Data were collected from 626 venues. Smoking was observed during almost one-third of visits with substantial differences between countries-from 5% in India to 72% in Chad. After excluding venues where other combustion sources were observed, secondhand smoke (SHS) derived PM2.5 was calculated by subtracting outdoor ambient PM2.5 concentrations from indoor measurements and was, on average, 34 ug/m(3) in venues with observed smoking-compared to an average value of 0 ug/m(3) in venues where smoking was not observed (P < .001). In over one-quarter of venues where smoking was observed the difference between indoor and outdoor PM2.5 concentrations exceeded 64 ug/m(3). CONCLUSIONS: This study suggests that low-cost air quality monitoring is a viable method for improving knowledge about environmental SHS and can provide indicative data on compliance with local and national SF legislation in hospitality venues in LMICs. IMPLICATIONS: Air quality monitoring can provide objective scientific data on SHS and air quality levels in venues to assess the effectiveness of SF laws and identify required improvements. Equipment costs and high outdoor air pollution levels have hitherto limited application in LMICs. This study tested the feasibility of using a validated low-cost methodology in hospitality venues in six LMIC urban settings and suggests this is a viable method for improving knowledge about SHS exposure and can provide indicative data on compliance with SF legislation. PMID- 26814195 TI - Rewilding. PMID- 26814197 TI - TCDD-inducible poly-ADP-ribose polymerase (TIPARP/PARP7) mono-ADP-ribosylates and co-activates liver X receptors. AB - Members of the poly-ADP-ribose polymerase (PARP) family catalyse the ADP ribosylation of target proteins and are known to play important roles in many cellular processes, including DNA repair, differentiation and transcription. The majority of PARPs exhibit mono-ADP-ribosyltransferase activity rather than PARP activity; however, little is known about their biological activity. In the present study, we report that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inducible poly-ADP-ribose polymerase (TIPARP), mono-ADP-ribosylates and positively regulates liver X receptor alpha (LXRalpha) and LXRbeta activity. Overexpression of TIPARP enhanced LXR-reporter gene activity. TIPARP knockdown or deletion reduced LXR regulated target gene expression levels in HepG2 cells and in Tiparp(-/-)mouse embryonic fibroblasts (MEFs) respectively. Deletion and mutagenesis studies showed that TIPARP's zinc-finger and catalytic domains were required to enhance LXR activity. Protein interaction studies using TIPARP and LXRalpha/beta peptide arrays revealed that LXRs interacted with an N-terminal sequence (a.a. 209-236) of TIPARP, which also overlapped with a putative co activator domain of TIPARP (a.a. 200-225). Immunofluorescence studies showed that TIPARP and LXRalpha or LXRbeta co-localized in the nucleus.In vitroribosylation assays provided evidence that TIPARP mono-ADP-ribosylated both LXRalpha and LXRbeta. Co-immunoprecipitation (co-IP) studies revealed that ADP-ribosylase macrodomain 1 (MACROD1), but not MACROD2, interacted with LXRs in a TIPARP dependent manner. This was complemented by reporter gene studies showing that MACROD1, but not MACROD2, prevented the TIPARP-dependent increase in LXR activity. GW3965-dependent increases in hepatic Srebp1 mRNA and protein expression levels were reduced in Tiparp(-/-)mice compared with Tiparp(+/+)mice. Taken together, these data identify a new mechanism of LXR regulation that involves TIPARP, ADP-ribosylation and MACROD1. PMID- 26814198 TI - A new home for the Journal of Cerebral Blood Flow and Metabolism. PMID- 26814199 TI - Corrigendum. AB - Pyroptotic neuronal cell death mediated by the AIM2 inflammasomeAdamczak SE, de Rivero Vaccari JP, Dale G, Brand FJ 3rd, Nonner D, Bullock MR, Dahl GP, Dietrich WD, Keane RWJournal of Cerebral Blood Flow & Metabolism 2014; 34: 621-629. PMID- 26814200 TI - Corrigendum. AB - The TNF-alpha/NF-kappaB signaling pathway has a key role in methamphetamine induced blood-brain barrier dysfunctionVanessa Coelho-Santos, Ricardo A Leitao, Filipa L Cardoso, Ines Palmela, Manuel Rito, Marcos Barbosa, Maria A Brito, Carlos A Fontes-Ribeiro and Ana P SilvaJournal of Cerebral Blood Flow & Metabolism 2015; 35: 1260-1271. PMID- 26814201 TI - Validity of visual perceptive computing for static posturography in patients with multiple sclerosis. AB - BACKGROUND: Multiple sclerosis (MS) patients frequently have postural control impairment but quantitative posturography is difficult to perform in clinical care. Recent technology facilitates new posturography approaches. OBJECTIVE: To evaluate construct validity of visual perceptive computing (VPC) for static posturography to study postural control in MS patients. METHODS: A total of 90 MS patients and 59 healthy controls (HCs) performed three stance tests: open, closed and tandem stance. Static posturography was performed using a VPC system with Microsoft Kinect. Clinical assessments included Expanded Disability Status Scale (EDSS), Timed-25-Foot-Walk, Short-Maximum-Speed-Walk and 12-item MS Walking Scale (MSWS-12) questionnaire. Reliability was assessed with intra-class correlation coefficients at retest. RESULTS: As a group, MS patients performed worse than HCs in all tests. The closed stance test showed best applicability and reliability. With closed eyes, in 36.7% of patients, the three-dimensional mean angular sway velocity (MSV-3D) was above HCs' 95th percentile. Higher MSV-3D was associated with decreased walking speed (p < 0.001); worse clinical scores, mainly attributable to the cerebellar functional system score (p < 0.001); and reflected in self-reported walking disability (MSWS-12, p < 0.001). CONCLUSION: Postural control can be reliably assessed by VPC-based static posturography in patients with MS. Abnormal postural control seems to predominantly reflect involvement of cerebellar circuits with impact on gait and walking disability. PMID- 26814202 TI - Oxidative stress and abdominal aortic aneurysm: potential treatment targets. AB - Abdominal aortic aneurysm (AAA) is a significant cause of mortality in older adults. A key mechanism implicated in AAA pathogenesis is inflammation and the associated production of reactive oxygen species (ROS) and oxidative stress. These have been suggested to promote degradation of the extracellular matrix (ECM) and vascular smooth muscle apoptosis. Experimental and human association studies suggest that ROS can be favourably modified to limit AAA formation and progression. In the present review, we discuss mechanisms potentially linking ROS to AAA pathogenesis and highlight potential treatment strategies targeting ROS. Currently, none of these strategies has been shown to be effective in clinical practice. PMID- 26814205 TI - NADPH oxidase 2 plays a role in experimental corneal neovascularization. AB - Corneal neovascularization, the growth of new blood vessels in the cornea, is a leading cause of vision impairment after corneal injury. Neovascularization typically occurs in response to corneal injury such as that caused by infection, physical trauma, chemical burns or in the setting of corneal transplant rejection. The NADPH oxidase enzyme complex is involved in cell signalling for wound-healing angiogenesis, but its role in corneal neovascularization has not been studied. We have now analysed the role of the Nox2 isoform of NADPH oxidase in corneal neovascularization in mice following chemical injury. C57BL/6 mice aged 8-14 weeks were cauterized with an applicator coated with 75% silver nitrate and 25% potassium nitrate for 8 s. Neovascularization extending radially from limbal vessels was observed in corneal whole-mounts from cauterized wild type mice and CD31+ vessels were identified in cauterized corneal sections at day 7. In contrast, in Nox2 knockout (Nox2 KO) mice vascular endothelial growth factor-A (Vegf-A), Flt1 mRNA expression, and the extent of corneal neovascularization were all markedly reduced compared with their wild type controls. The accumulation of Iba-1+ microglia and macrophages in the cornea was significantly less in Nox2 KO than in wild type mice. In conclusion, we have demonstrated that Nox2 is implicated in the inflammatory and neovascular response to corneal chemical injury in mice and clearly VEGF is a mediator of this effect. This work raises the possibility that therapies targeting Nox2 may have potential for suppressing corneal neovascularization and inflammation in humans. PMID- 26814206 TI - Transoral Surgical Anatomy and Clinical Considerations of Lateral Oropharyngeal Wall, Parapharyngeal Space, and Tongue Base. AB - OBJECTIVE: With the emergence of transoral robotic approaches, head and neck surgeons are faced with an unfamiliar inside-out head and neck anatomy. This study was performed to describe key anatomic landmarks and surgical considerations of transoral robotic resection of the lateral oropharyngeal wall, the parapharyngeal space, and the base of the tongue. STUDY DESIGN: Descriptive transoral anatomic study. SETTING: Academic anatomy laboratory and tertiary academic hospital. SUBJECTS AND METHODS: Transoral dissections of the lateral pharyngeal wall, base of tongue, and parapharyngeal space were performed in 5 vascular silicone-injected cadavers to illustrate anatomic landmarks from the inside-out perspective. Lateral neck dissections were also performed to better appreciate the anatomic structures and to be more familiar with intraoperative anatomy. RESULTS: The neurovascular and muscular structures located in parapharyngeal space, lateral oropharyngeal wall, and base of tongue were described. Surgical significance of key anatomic landmarks was emphasized with high-quality illustrations. CONCLUSION: A thorough understanding of transoral anatomy is crucial to perform transoral robotic surgery safely and efficiently. To understand inside-out anatomy of base of tongue, lateral oropharyngeal wall, and parapharyngeal space, cadaveric dissection is highly beneficial and may help to shorten the learning curve for transoral robotic dissections. PMID- 26814207 TI - A Not So Lucky Penny. PMID- 26814204 TI - Gender differences in developmental programming of cardiovascular diseases. AB - Hypertension is a risk factor for cardiovascular disease, the leading cause of death worldwide. Although multiple factors contribute to the pathogenesis of hypertension, studies by Dr David Barker reporting an inverse relationship between birth weight and blood pressure led to the hypothesis that slow growth during fetal life increased blood pressure and the risk for cardiovascular disease in later life. It is now recognized that growth during infancy and childhood, in addition to exposure to adverse influences during fetal life, contributes to the developmental programming of increased cardiovascular risk. Numerous epidemiological studies support the link between influences during early life and later cardiovascular health; experimental models provide proof of principle and indicate that numerous mechanisms contribute to the developmental origins of chronic disease. Sex has an impact on the severity of cardiovascular risk in experimental models of developmental insult. Yet, few studies examine the influence of sex on blood pressure and cardiovascular health in low-birth weight men and women. Fewer still assess the impact of ageing on sex differences in programmed cardiovascular risk. Thus, the aim of the present review is to highlight current data about sex differences in the developmental programming of blood pressure and cardiovascular disease. PMID- 26814208 TI - Variable Findings for Drug-Induced Sleep Endoscopy in Obstructive Sleep Apnea with Propofol versus Dexmedetomidine. AB - OBJECTIVE: To compare VOTE classification findings (velum, oropharyngeal-lateral walls, tongue base, and epiglottis) for drug-induced sleep endoscopy (DISE) among patients with obstructive sleep apnea (OSA) using 2 sedation protocols. STUDY DESIGN: Case series with chart review. SETTING: Single tertiary institution. SUBJECTS: Patients with OSA who underwent DISE. METHODS: A total of 216 patients underwent DISE between November 23, 2011, and May 1, 2015. DISE findings based on VOTE classification were compared between patients receiving the propofol- and dexmedetomidine-based sedation protocols. RESULTS: Patients with OSA (N = 216; age, 44.3 +/- 11.7 years; body mass index, 27.9 +/- 4.8 kg/m(2)) underwent DISE with intravenous administration of propofol (n = 52) or dexmedetomidine (n = 164). There were no statistically significant differences between the 2 groups in baseline apnea-hypopnea index, oxygen desaturation index, Mallampati score, tonsil size, Epworth Sleepiness Scale score, peripheral oxygen saturation nadir, age, sex, or body mass index. Patients in the propofol group had a significantly increased likelihood of demonstrating complete tongue base obstruction (75%, 39 of 52) versus partial or no obstruction (25%, 13 of 52) in the anterior-posterior dimension, as compared with the dexmedetomidine group (complete obstruction: 42.7%, 70 of 164; partial or no obstruction: 57.3%, 94 of 164; odds ratio: 4.0; 95% confidence interval: 2.0-8.1; P = .0001). Obstruction of other airway subsites was not significantly different. CONCLUSION: Use of propofol versus dexmedetomidine to induce sedation may have a significant effect on the pattern of upper airway obstruction observed during DISE. Randomized prospective studies are indicated to confirm these initial findings. PMID- 26814203 TI - NADPH oxidases: key modulators in aging and age-related cardiovascular diseases? AB - Reactive oxygen species (ROS) and oxidative stress have long been linked to aging and diseases prominent in the elderly such as hypertension, atherosclerosis, diabetes and atrial fibrillation (AF). NADPH oxidases (Nox) are a major source of ROS in the vasculature and are key players in mediating redox signalling under physiological and pathophysiological conditions. In this review, we focus on the Nox-mediated ROS signalling pathways involved in the regulation of 'longevity genes' and recapitulate their role in age-associated vascular changes and in the development of age-related cardiovascular diseases (CVDs). This review is predicated on burgeoning knowledge that Nox-derived ROS propagate tightly regulated yet varied signalling pathways, which, at the cellular level, may lead to diminished repair, the aging process and predisposition to CVDs. In addition, we briefly describe emerging Nox therapies and their potential in improving the health of the elderly population. PMID- 26814209 TI - The dynamic steroid landscape of equine pregnancy mapped by mass spectrometry. AB - Liquid chromatography-tandem mass spectrometry (LC-MS/MS) allowed comprehensive analysis of various steroids detectable in plasma throughout equine gestation. Mares (n=9) were bled serially until they foaled. Certain steroids dominated the profile at different stages of gestation, clearly defining key physiological and developmental transitions. The period (weeks 6-20) coincident with equine chorionic gonadotropic (eCG) stimulation of primary corpora lutea and subsequent formation of secondary luteal structures was defined by increased progesterone, 17OH-progesterone and androstenedione, all Delta4 steroids. The 5alpha-reduced metabolite of progesterone, dihydroprogesterone (DHP) paralleled progesterone secretion at less than half the concentration until week 12 of gestation when progesterone began to decline but DHP concentrations continued to increase. DHP exceeded progesterone concentrations by week 16, clearly defining the luteo placental shift in pregnane synthesis from primarily ovarian to primarily placental. The period corresponding to the growth of fetal gonads was defined by increasing dehydroepiandrosterone and pregnenolone (Delta5 steroids) concentrations from week 14, peaking at week 34 and declining to term. Metabolites of DHP (including allopregnanolone) dominated the steroid profile in late gestation, some exceeding DHP by weeks 13 or 14 and near term by almost tenfold. Thus Delta4 steroids dominated during ovarian stimulation by eCG, inversion of the ratio of progesterone: DHP (increasing 5alpha-pregnanes) marked the luteo-placental shift, Delta5 steroids defined fetal gonadal growth and 5alpha-reduced metabolites of DHP dominated the steroid profile in mid- to late gestation. Comprehensive LC-MS/MS steroid analysis provides opportunities to better monitor the physiology and the progress of equine pregnancies, including fetal development. PMID- 26814210 TI - High-fat diets exaggerate endocrine and metabolic phenotypes in a rat model of DHEA-induced PCOS. AB - Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder with unclear etiology and unsatisfactory management. Effects of diets on the phenotype of PCOS were not fully understood. In the present study, we applied 45 and 60% high-fat diets (HFDs) on a rat model of PCOS induced by postnatal DHEA injection. We found that both DHEA and DHEA+HFDs rats exhibited reproductive abnormalities, including hyperandrogenism, irregular cycles and polycystic ovaries. The addition of HFDs, especially 60% HFDs, exaggerated morphological changes of ovaries and a number of metabolic changes, including increased body weight and body fat content, impaired glucose tolerance and increased serum insulin levels. Results from qPCR showed that DHEA-induced increased expression of hypothalamic androgen receptor and LH receptor were reversed by the addition of 60% HFDs. In contrast, the ovarian expression of LH receptor and insulin receptor mRNA was upregulated only with the addition of 60% HFDs. These findings indicated that DHEA and DHEA+HFDs might influence PCOS phenotypes through distinct mechanisms: DHEA affects the normal function of hypothalamus-pituitary ovarian axis through LH, whereas the addition of HFDs exaggerated endocrine and metabolic dysfunction through ovarian responses to insulin-related mechanisms. We concluded that the addition of HFDs yielded distinct phenotypes of DHEA-induced PCOS and could be used for studies on both reproductive and metabolic features of the syndrome. PMID- 26814211 TI - Evaluation of Heating and Shearing on the Viscoelastic Properties of Calcium Hydroxyapatite Used in Injection Laryngoplasty. AB - OBJECTIVE: To compare the viscoelastic properties of calcium hydroxyapatite (CaHA) to carboxymethylcellulose (CMC) injectables used for injection laryngoplasty and determine if they are affected by heating and shearing. STUDY DESIGN: Experimental. SETTING: University laboratory. SUBJECTS AND METHODS: Vocal fold injection laryngoplasty with CaHA is oftentimes challenging due to the amount of pressure necessary to push the injectate through a needle. Anecdotal techniques, such as heating the product, have been suggested to facilitate injection. The viscoelastic properties of CaHA and CMC were measured with a rheometer. The effects of heating and shearing on sample viscoelasticity were recorded. RESULTS: CaHA was 9.5 times more viscous than CMC (43,100 vs 4540 Pa.s). Heating temporarily decreased the viscosity of CaHA by 32%. However, it also caused the viscosity to subsequently increase after time. Shearing of CaHA reduced its viscosity by 26%. Heating and shearing together temporarily reduced the viscosity of CaHA by 52%. CONCLUSION: A combination of heating and shearing had a more profound effect than heating or shearing alone on the viscosity of CaHA, potentially making it easier to inject temporarily. Long-term and in vivo studies are required to further analyze the effect of heating and shearing on CaHA injectables. PMID- 26814212 TI - A service evaluation of an integrated model of palliative care of cystic fibrosis. AB - BACKGROUND: Patients with advanced cystic fibrosis have severe symptoms with a complex trajectory of exacerbations and recovery. They are often awaiting lung transplantation, and many die without receiving specialist palliative care. AIM: We introduced an integrated model whereby palliative specialists joined the cystic fibrosis team to provide palliative care in parallel with standard care. DESIGN: A service evaluation of this model of care was undertaken in a prospective case series documenting symptoms and outcomes, the views of the cystic fibrosis team and the experience of the palliative specialists. SETTING/PARTICIPANTS: Over 3 years, 28 (10%) of 282 patients attending the cystic fibrosis centre had specialist palliative care. RESULTS: They had advanced lung disease (mean forced expiratory volume in 1 s (FEV1) = 0.86 L (25% predicted)), and 17 died: 6 were on a transplant waiting list at death; 10 were unsuitable and 1 died post transplantation. All who died over these 3 years had specialist palliative care. Four patients had successful transplants. Assessment showed a high prevalence of breathlessness, cough, pain, vomiting and fatigue, with a significant impact on daily life. The cystic fibrosis team rated this model of care highly, felt that palliative care should be members of the team, and thought that patients had found it helpful. The palliative specialists gained knowledge of cystic fibrosis, found it beneficial to meet patients earlier in the disease, and identified unmet needs in managing bereavement and the effects of deaths on other patients with cystic fibrosis. CONCLUSION: This model has been successful in overcoming the difficulties in access to specialist palliative care for patients with cystic fibrosis. PMID- 26814213 TI - Gender and family caregiving at the end-of-life in the context of old age: A systematic review. AB - BACKGROUND: As societies age and governments attempt to manage within constrained health budgets by moving care into community settings, women will be called upon to provide more palliative care in old age. However, little is known about gendered disparities for caregivers of people over the age of 65 years. AIM: To identify and synthesise the empirical literature between 1994 and 2014 that focusses on gender and family caregiving for people over the age of 65 years with a life-limiting illness. DESIGN: Systematic review of qualitative and quantitative studies conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Supplemental review using a novel feminist quality appraisal framework. DATA SOURCES: Search of MEDLINE, CINAHL, PsycINFO, Sociological Abstracts and Gender Studies to find empirical studies on gender and family caregiving at end-of-life in the context of old age. RESULTS: Of 19 studies identified, 9 presented thorough gender analyses. Gender themes included why people care, how they care, and the consequences of providing care. Women caregivers experienced a greater degree of mental and physical strain than their male counterparts. This was linked to societal expectation that women should provide a greater degree of care at the end-of-life for family members. CONCLUSION: Palliative family caregiving for older adults is gendered. Gender affects why people care and the consequences of providing care. Palliative care literature needs to incorporate a greater gender focus for future research and policy makers need to be aware of the gendered ramifications of providing more palliative care in the community. PMID- 26814214 TI - Differences in palliative care quality between patients with cancer, patients with organ failure and frail patients: A study based on measurements with the Consumer Quality Index Palliative Care for bereaved relatives. AB - BACKGROUND: Palliative care is rooted in the care for incurably ill cancer patients. Yet today there is a recognised need for palliative care for patients with non-cancer conditions. However, the often unpredictable illness trajectories and the difficulty in predicting the imminence of death in people with non-cancer conditions may hamper the provision of high-quality palliative care. AIM: To compare the quality of palliative care provided to patients with cancer, patients with organ failure and frail patients and their relatives. DESIGN: An existing dataset was analysed, consisting of data collected through the Consumer Quality Index Palliative Care questionnaire for bereaved relatives. SETTING/PARTICIPANTS: Data were analysed of 456 relatives of deceased patients with cancer, patients with organ failure and frail patients from various care settings in the Netherlands. RESULTS: Relatives (e.g. partners or children) of deceased patients with organ failure (n = 61) were more likely to have negative experiences regarding the expertise of healthcare professionals compared with relatives of patients with cancer (n = 215). Relatives of frail patients (n = 180) gave a relatively low rating of the general quality of the care in the last week of the patient's life, both as regards the care provided to patients (p = 0.015) and as regards the support to relatives (p = 0.009). CONCLUSION: Compared with the bereaved relatives of patients with cancer, bereaved relatives of patients with organ failure or frailty were more likely to negatively assess the palliative care provided to both the patient and themselves. Improving professionals' expertise in palliative care for people with non-cancer conditions is recommended. PMID- 26814215 TI - A survey of views and practice patterns of dialysis medical directors toward end of-life decision making for patients with end-stage renal disease. AB - BACKGROUND: Patients with end-stage renal disease report infrequent end-of-life discussions, and nephrology trainees report feeling unprepared for end-of-life decision making, but the views of dialysis medical directors have not been studied. AIM: Our objective is to understand dialysis medical directors' views and practice patterns on end-of-life decision making for patients with ESRD. DESIGN: We administered questionnaires to dialysis medical directors during medical director meetings of three different dialysis organizations in 2013. Survey questions corresponded to recommendations from the Renal Physicians Association clinical practice guidelines on initiation and withdrawal of dialysis. SETTING/PARTICIPANTS: There were 121 medical director respondents from 28 states. RESULTS: The majority of respondents felt "very prepared" (66%) or "somewhat prepared" (29%) to participate in end-of-life decisions and most (80%) endorsed a model of shared decision making. If asked to do so, 70% of the respondents provided prognostic information "often" or "nearly always." For patients with a poor prognosis, 36% of respondents would offer a time-limited trial of dialysis "often" or "nearly always", while 56% of respondents would suggest withdrawal from dialysis "often" or "nearly always" for those with a poor prognosis currently receiving dialysis therapy. Patient resistance and fear of taking away hope were the most commonly cited barriers to end-of-life discussions. CONCLUSION: Views and reported practice patterns of medical directors are consistent with clinical practice guidelines for end-of-life decision making for patients with end-stage renal disease but inconsistent with patient perceptions. PMID- 26814216 TI - Hospice assist at home: does the integration of hospice care in primary healthcare support patients to die in their preferred location - A retrospective cross-sectional evaluation study. AB - BACKGROUND: A majority of patients prefer to die at home. Specialist palliative care aims to improve quality of life. Hospice assist at home is a Dutch model of general/specialised palliative care within primary care, collaboratively built by general practitioners and a hospice. AIM: The aims of this study are to explore whether hospice assist at home service enables patients at hometo express end-of life preferences and die in their preferred location. In addition, this study provides insight into symptomburden, stability and early referral. DESIGN: A retrospective cross-sectional evaluation study was performed (December 2014-March 2015), using hospice assist at home patient records and documentation. Primary outcome includes congruence between preferred and actual place of death. Secondary outcomes include symptom burden, (in)stability and early identification. SETTING/PARTICIPANTS: Between June 2012 and December 2014, 130 hospice assist at home patients, living at home with a life expectancy <1 year, were enrolled. Hospice assist at home, a collaboration between general practitioners, district nurses, trained volunteers and a hospice team, facilitates (1) general practitioner-initiated consultation by Nurse Consultant Hospice, (2) fortnightly interdisciplinary consultations and (3) 24/7 hospice backup for patients, caregivers and professionals. RESULTS: A total of 130 patients (62 (48%) men; mean age, 72 years) were enrolled, of whom 107/130 (82%) died and 5 dropped out. Preferred place of death was known for 101/107 (94%) patients of whom 91% patients died at their preferred place of death. CONCLUSION: Hospice assist at home service supports patients to die in their preferred place of death. Shared responsibility of proactive care in primary care collaboration enabled patients to express preferences. Hospice care should focus on local teamwork, to contribute to shared responsibilities in providing optimal palliative care. PMID- 26814217 TI - Fat-Free Mass Index for Evaluating the Nutritional Status and Disease Severity in COPD. AB - BACKGROUND: Despite the high prevalence of weight loss in subjects with COPD, the 2011 COPD management guidelines do not include an index measuring nutritional status. Fat-free mass index (FFMI) can accurately determine the nutritional status of subjects and may be closely correlated with COPD severity. We aimed to determine the nutritional status evaluated by FFMI according to the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) levels in stable subjects with COPD and the association between nutritional status and respiratory symptoms, exercise capacity, and respiratory muscle function. METHODS: We included 235 stable subjects with COPD in this cross-sectional study. All of the subjects were divided into the 2011 GOLD Groups A, B, C, and D. FFMI (measured by bioelectrical impedance), spirometry (FEV1, percent-of-predicted FEV1, and FEV1/FVC), respiratory muscle function (peak inspiratory and peak expiratory pressures), exercise capacity (6-min walk distance), and dyspnea severity (Modified Medical Research Council dyspnea scale) were measured and compared between the GOLD groups. RESULTS: Malnutrition was identified in 48.5% of subjects and most prevalent in Group D (Group A: 41%, Group B: 41%, Group C: 31%, and Group D: 62%). FFMI was significantly lower in Group D (P < .001), with both sexes considered malnourished. Low FFMI significantly correlated with frequent exacerbation, older age, decreased pulmonary function, 6-min walk distance, peak inspiratory pressure, and worsened dyspnea. FFMI was significantly lower in the emphysema-dominant phenotype and mixed phenotype compared with the normal phenotype and airway-dominant phenotype. A stepwise multiple linear regression analysis identified peak inspiratory pressures and older age as independent predictors of FFMI. CONCLUSIONS: Malnutrition is highly prevalent in all COPD groups, particularly in Group D subjects, who warrant special attention for nutritional intervention and pulmonary rehabilitation. FFMI significantly correlated with exercise capacity, dyspnea, respiratory muscle function, and pulmonary function and may be a useful predictor of COPD severity. PMID- 26814218 TI - Ultrasonographic Assessment of Diaphragm Function in Critically Ill Subjects. AB - The majority of patients admitted to the ICU require mechanical ventilation as a part of their process of care. However, mechanical ventilation itself or the underlying disease can lead to dysfunction of the diaphragm, a condition that may contribute to the failure of weaning from mechanical ventilation. However, extended time on the ventilator increases health-care costs and greatly increases patient morbidity and mortality. Nevertheless, symptoms and signs of muscle disease in a bedridden (or bed rest-only) ICU patient are often difficult to assess because of concomitant confounding factors. Conventional assessment of diaphragm function lacks specific, noninvasive, time-saving, and easily performed bedside tools or requires patient cooperation. Recently, the use of ultrasound has raised great interest as a simple, noninvasive method of quantification of diaphragm contractile activity. In this review, we discuss the physiology and the relevant pathophysiology of diaphragm function, and we summarize the recent findings concerning the evaluation of its (dys)function in critically ill patients, with a special focus on the role of ultrasounds. We describe how to assess diaphragm excursion and diaphragm thickening during breathing and the meaning of these measurements under spontaneous or mechanical ventilation as well as the reference values in health and disease. The spread of ultrasonographic assessment of diaphragm function may possibly result in timely identification of patients with diaphragm dysfunction and to a potential improvement in the assessment of recovery from diaphragm weakness. PMID- 26814219 TI - Out-Patient Pulmonary Rehabilitation Improves Medial-Lateral Balance in Subjects With Chronic Respiratory Disease: Proof-of-Concept Study. AB - BACKGROUND: Recent studies show balance impairment in subjects with chronic respiratory disease. The aim of this proof-of-concept study was to investigate clinical and quantitative measures of balance in people with chronic respiratory disease following participation in an out-patient pulmonary rehabilitation (PR) program to better understand features of balance improvement. A secondary aim was to probe possible mechanisms for balance improvement to provide the foundation for optimal design of future studies. METHODS: Eleven individuals with chronic respiratory disease enrolled in an 8-week out-patient PR program participated. Standing balance, measured with a force plate, in the medial-lateral and anterior posterior directions with eyes open and closed was assessed with linear (SD and sway path length) and non-linear (diffusion analysis) center-of-pressure measures. Balance was evaluated clinically with the Timed Up and Go and Four Square Step Test. Fear of falling and balance confidence were assessed with questionnaires. RESULTS: After participation in PR, medial-lateral sway path length decreased (P = .031), and center-of-pressure diffusion in the medial lateral direction was slower (P = .02) and traveled over less distance (P = .03) with eyes closed. This suggests greater control of medial-lateral sway. There was no change in anterior-posterior balance (P > .067). Performance improved on the Timed Up and Go (median [interquartile range] pre-PR = 9.4 [7.9-12.8] vs. post-PR = 8.1 [7.3-12.2] s, P = .003) and Four Square Step Test (median [interquartile range] pre-PR = 9.3 [7.2-14.2] vs. post-PR = 8.7 [7.4-10.2] s, P = .050). There were no changes in balance confidence (P = .72) or fear of falling (P = .57). CONCLUSIONS: Participation in an 8-week out-patient PR program improved balance, as assessed by clinical and laboratory measures. Detailed analysis of force plate measures demonstrated improvements primarily with respect to medial-lateral balance control. These data provide a basis for the development of larger scale studies to investigate the mechanisms for medial-lateral balance improvements following PR and to determine how PR may be refined to enhance balance outcomes in this population. (ClinicalTrials.gov registration NCT00864084.). PMID- 26814220 TI - Flexible Bronchoscopy Is Safe and Effective in Adult Subjects Supported With Extracorporeal Membrane Oxygenation. AB - BACKGROUND: Previous studies have demonstrated the safety of flexible bronchoscopy (FB) in mechanically ventilated subjects. However, the safety of FB in adult subjects receiving extracorporeal membrane oxygenation (ECMO) has not been described previously. METHODS: A retrospective review was conducted of all adult subjects who underwent FB while receiving ECMO support at the University of Alabama at Birmingham Hospital from January 1, 2013, to December 31, 2014. Physiologic variables, pre- and post-FB ECMO, and ventilator settings were recorded. RESULTS: 79 adult subjects underwent FB receiving ECMO with a total of 223 bronchoscopies. The most common indications for bronchoscopy included diagnostic evaluation of infection in subjects with pneumonia (29%) and clearance of excessive secretions (22%). In 70% of subjects, moderate or greater amounts of secretions were noted. FB yielded positive culture data in 37 subjects (47%), which resulted in a change to the antibiotic regimen in 14 subjects (38%) with positive culture data. No significant differences in mean PaO2 /FIO2 , mean ECMO flow, mean sweep gas, ventilator settings, or hemodynamic parameters (heart rate, oxygen saturation, and mean blood pressure) were noted before and after FB. Complications were mild and transient: blood-tinged secretions after FB in 21% cases, which resolved spontaneously, intraprocedural hypoxemia in 2.2% of cases, and dysrhythmia in <1% of cases. There were no episodes of ECMO cannula dislodgement or inadvertent extubation. CONCLUSIONS: FB can be used safely in adult subjects supported with ECMO and is not associated with significant hemodynamics changes, bleeding, or mechanical complications during ECMO support. PMID- 26814221 TI - Body Mass Index-Dependent Ventilatory Parameters From Respiratory Inductive Plethysmography During 6-Minute Walk Test. AB - BACKGROUND: Walking is part of obesity management. Assessment of ventilatory impairments and consequences for gait induced by obesity could be clinically helpful. We aimed to develop a method to accurately monitor ventilation with respiratory inductive plethysmography (RIP) in subjects with high body mass indices (BMIs) during a 6-min walk test (6MWT). METHODS: 25 volunteers were divided into 2 groups based on BMI (<25 or >30 kg/m2) and performed a 6MWT with a calibrated RIP. Ventilatory parameters (tidal volume [V(T)], inspiratory [T(I)] and expiratory [T(E)] times, V(T)/T(I) ratio, and T(I)/Ttot ratio) were determined after processing RIP signals with a custom-made algorithm designed to discriminate tissue motion artifacts and respiratory cycles in the time domain. Six-min walk distance and average speed by minute were collected. RESULTS: The number of artifacts removed by the algorithm used for artifact removal was higher for high-BMI subjects and was correlated to their individual values (r = 0.66, P < .001). Six-min walk distance was lower for the group with a higher BMI (P = .001). ANOVA revealed effects of exercise for V(T), T(I), and T(E) (P < .001) and also BMI effects in the course of the 6MWT for V(T), T(I), T(E), V(T)/T(I), and T(I)/Ttot (P < .001 for each of them). CONCLUSIONS: This respiratory monitoring method is sufficiently sensitive to point out differences between rest and exercise as well as locomotor and ventilatory differences relative to BMI during the 6MWT. Thus, this system gives useful information from the 6MWT for clinicians who want to assess respiratory patterns of patients during this commonly used test. PMID- 26814222 TI - Ventilator-Related Adverse Events: A Taxonomy and Findings From 3 Incident Reporting Systems. AB - BACKGROUND: In 2009, researchers from Johns Hopkins University's Armstrong Institute for Patient Safety and Quality; public agencies, including the FDA; and private partners, including the Emergency Care Research Institute and the University HealthSystem Consortium (UHC) Safety Intelligence Patient Safety Organization, sought to form a public-private partnership for the promotion of patient safety (P5S) to advance patient safety through voluntary partnerships. The study objective was to test the concept of the P5S to advance our understanding of safety issues related to ventilator events, to develop a common classification system for categorizing adverse events related to mechanical ventilators, and to perform a comparison of adverse events across different adverse event reporting systems. METHODS: We performed a cross-sectional analysis of ventilator-related adverse events reported in 2012 from the following incident reporting systems: the Pennsylvania Patient Safety Authority's Patient Safety Reporting System, UHC's Safety Intelligence Patient Safety Organization database, and the FDA's Manufacturer and User Facility Device Experience database. Once each organization had its dataset of ventilator-related adverse events, reviewers read the narrative descriptions of each event and classified it according to the developed common taxonomy. RESULTS: A Pennsylvania Patient Safety Authority, FDA, and UHC search provided 252, 274, and 700 relevant reports, respectively. The 3 event types most commonly reported to the UHC and the Pennsylvania Patient Safety Authority's Patient Safety Reporting System databases were airway/breathing circuit issue, human factor issues, and ventilator malfunction events. The top 3 event types reported to the FDA were ventilator malfunction, power source issue, and alarm failure. CONCLUSIONS: Overall, we found that (1) through the development of a common taxonomy, adverse events from 3 reporting systems can be evaluated, (2) the types of events reported in each database were related to the purpose of the database and the source of the reports, resulting in significant differences in reported event categories across the 3 systems, and (3) a public private collaboration for investigating ventilator-related adverse events under the P5S model is feasible. PMID- 26814223 TI - Queen pheromones modulate DNA methyltransferase activity in bee and ant workers. AB - DNA methylation is emerging as an important regulator of polyphenism in the social insects. Research has concentrated on differences in methylation between queens and workers, though we hypothesized that methylation is involved in mediating other flexible phenotypes, including pheromone-dependent changes in worker behaviour and physiology. Here, we find that exposure to queen pheromone affects the expression of two DNA methyltransferase genes in Apis mellifera honeybees and in two species of Lasius ants, but not in Bombus terrestris bumblebees. These results suggest that queen pheromones influence the worker methylome, pointing to a novel proximate mechanism for these key social signals. PMID- 26814225 TI - 'Neo-Europe' and its ecological consequences: the example of systematic degradation in Australia's inland fisheries. AB - The antiquity of human impact on ecosystems is increasingly understood, though the arrival of settlers to new lands remains a defining period. Colonization of the 'neo-Europes', a reference from the discipline of history, precipitated changes in aquatic ecosystems through modification of waterways and introductions of non-native species. We considered historical fisheries and fish market records from South Australia (1900-1946) against contemporary production statistics (1987 2011). Native inland species historically contributed large quantities to the market but have deteriorated such that fishing is now limited, and conservation regulations exist. This pattern mirrors the demand-driven transition from freshwater to marine fisheries in Europe; hence, we propose that this pattern was predicated on societal expectations and that European settlement and introduction of non-native fishes led to systematic overexploitation and degradation of native inland fisheries species in Australia, representing a further consequence of neo European colonization to ecology. Accurate interpretation of ecological change can ensure more appropriate management intervention. Concepts, such as neo Europe, from alternative disciplines can inform the recognition and evaluation of patterns at regional and global scales. PMID- 26814224 TI - Can women detect cues to ovulation in other women's faces? AB - Recent research suggests that men find portraits of ovulatory women more attractive than photographs of the same women taken during the luteal phase. Only few studies have investigated whether the same is true for women. The ovulatory phase matters to men because women around ovulation are most likely to conceive, and might matter to women because fertile women might pose a reproductive threat. In an online study 160 women were shown face pairs, one of which was assimilated to the shape of a late follicular prototype and the other to a luteal prototype, and were asked to indicate which face they found more attractive. A further 60 women were tested in the laboratory using a similar procedure. In addition to choosing the more attractive face, these participants were asked which woman would be more likely to steal their own date. Because gonadal hormones influence competitive behaviour, we also examined whether oestradiol, testosterone and progesterone levels predict women's choices. The women found neither the late follicular nor the luteal version more attractive. However, naturally cycling women with higher oestradiol levels were more likely to choose the ovulatory woman as the one who would entice their date than women with lower oestradiol levels. These results imply a role of oestradiol when evaluating other women who are competing for reproduction. PMID- 26814226 TI - Blood transcriptomes reveal novel parasitic zoonoses circulating in Madagascar's lemurs. AB - Zoonotic diseases are a looming threat to global populations, and nearly 75% of emerging infectious diseases can spread among wildlife, domestic animals and humans. A 'One World, One Health' perspective offers us an ideal framework for understanding and potentially mitigating the spread of zoonoses, and the island of Madagascar serves as a natural laboratory for conducting these studies. Rapid habitat degradation and climate change on the island are contributing to more frequent contact among humans, livestock and wildlife, increasing the potential for pathogen spillover events. Given Madagascar's long geographical isolation, coupled with recent and repeated introduction of agricultural and invasive species, it is likely that a number of circulating pathogens remain uncharacterized in lemur populations. Thus, it is imperative that new approaches be implemented for de novo pathogen discovery. To this end, we used non-targeted deep sequencing of blood transcriptomes from two species of critically endangered wild lemurs (Indri indri and Propithecus diadema) to characterize blood-borne pathogens. Our results show several undescribed vector-borne parasites circulating within lemurs, some of which may cause disease in wildlife, livestock and humans. We anticipate that advanced methods for de novo identification of unknown pathogens will have broad utility for characterizing other complex disease transmission systems. PMID- 26814227 TI - Measurement of Workplace Violence Reporting. PMID- 26814229 TI - A Review of Design and Policy Interventions to Promote Nurses' Restorative Breaks in Health Care Workplaces. AB - The nursing profession in the United States is on the precipice of a crisis. Nurses are essential to the health care industry, and maintaining quality nursing care is a primary concern of today's health care managers. Health care facilities report high rates of staff burnout and turnover, and interest in the nursing profession among younger students is declining. Health care leaders must improve nurses' job satisfaction, performance, and retention. However, they often overlook the need for nurses' respite and underestimate the value of well designed staff break areas. An exhaustive and systematic literature search was conducted in the summer of 2014, and all studies found on the topic were reviewed for their relevance and quality of evidence. The existing literature about the main causes of nurses' fatigue, barriers that prevent nurses from taking restorative breaks, and consequences of nurses' fatigue for staff, patient, and facility outcomes demonstrates the pressing need for interventions that improve nurses' working conditions. Additional literature on the restorative effects of breaks and the value of well-designed break areas indicates that efforts to improve breakroom design can play an important role in improving nurses' job satisfaction and performance. PMID- 26814228 TI - Response to Letter to the Editor, "Measurement of Workplace Violence Reporting". PMID- 26814232 TI - Identification of Fic-1 as an enzyme that inhibits bacterial DNA replication by AMPylating GyrB, promoting filament formation. AB - The morphology of bacterial cells is important for virulence, evasion of the host immune system, and coping with environmental stresses. The widely distributed Fic proteins (filamentation induced by cAMP) are annotated as proteins involved in cell division because of the presence of the HPFx[D/E]GN[G/K]R motif. We showed that the presence of Fic-1 from Pseudomonas fluorescens significantly reduced the yield of plasmid DNA when expressed in Escherichia coli or P. fluorescens. Fic-1 interacted with GyrB, a subunit of DNA gyrase, which is essential for bacterial DNA replication. Fic-1 catalyzed the AMPylation of GyrB at Tyr(109), a residue critical for binding ATP, and exhibited auto-AMPylation activity. Mutation of the Fic-1 auto-AMPylated site greatly reduced AMPylation activity toward itself and toward GyrB. Fic-1-dependent AMPylation of GyrB triggered the SOS response, indicative of DNA replication stress or DNA damage. Fic-1 also promoted the formation of elongated cells when the SOS response was blocked. We identified an alpha-inhibitor protein that we named anti-Fic-1 (AntF), encoded by a gene immediately upstream of Fic-1. AntF interacted with Fic-1, inhibited the AMPylation activity of Fic-1 for GyrB in vitro, and blocked Fic-1-mediated inhibition of DNA replication in bacteria, suggesting that Fic-1 and AntF comprise a toxin-antitoxin module. Our work establishes Fic-1 as an AMPylating enzyme that targets GyrB to inhibit DNA replication and may target other proteins to regulate bacterial morphology. PMID- 26814231 TI - Cholesterol modulates Orai1 channel function. AB - STIM1 (stromal interaction molecule 1) and Orai proteins are the essential components of Ca(2+) release-activated Ca(2+) (CRAC) channels. We focused on the role of cholesterol in the regulation of STIM1-mediated Orai1 currents. Chemically induced cholesterol depletion enhanced store-operated Ca(2+) entry (SOCE) and Orai1 currents. Furthermore, cholesterol depletion in mucosal-type mast cells augmented endogenous CRAC currents, which were associated with increased degranulation, a process that requires calcium influx. Single point mutations in the Orai1 amino terminus that would be expected to abolish cholesterol binding enhanced SOCE to a similar extent as did cholesterol depletion. The increase in Orai1 activity in cells expressing these cholesterol binding-deficient mutants occurred without affecting the amount in the plasma membrane or the coupling of STIM1 to Orai1. We detected cholesterol binding to an Orai1 amino-terminal fragment in vitro and to full-length Orai1 in cells. Thus, our data showed that Orai1 senses the amount of cholesterol in the plasma membrane and that the interaction of Orai1 with cholesterol inhibits its activity, thereby limiting SOCE. PMID- 26814233 TI - Functional redundancy of the kinases MEK1 and MEK2: Rescue of the Mek1 mutant phenotype by Mek2 knock-in reveals a protein threshold effect. AB - The mammalian genome contains two mitogen-activated protein kinase (MAPK) kinase (MEK)-encoding genes, Mek1 and Mek2. MEKs phosphorylate and activate the two extracellular signal-regulated kinase (ERK) isoforms ERK1 and ERK2. Mek1(-/-) embryos die due to placental defects, whereas Mek2(-/-) mice survive with a normal life span and fertility, suggesting that MEK1 has functions not shared by MEK2. However, most Mek1(+/-)Mek2(+/-) embryos also die from placental defects, indicating that both Mek genes contribute to placental development. To assess the functional specificity of the Mek1 and Mek2 genes, we produced a Mek1 knock-in allele in which the Mek2 coding sequences were placed under the control of Mek1 regulatory sequences (Mek1(2) allele). Mek1(2/2) mice were viable with no apparent phenotype, indicating rescue by MEK2 and functional redundancy between the two MEK proteins. However, Mek1(2/-) embryos with Mek2 in only one of the Mek1 alleles and the other Mek1 allele null died from abnormal placenta, suggesting a dosage effect. Analysis of mice from a Mek1 Mek2 allelic series revealed that the occurrence of the placenta phenotype correlated with the amount of MEK protein independently of which MEK isoform was produced. Thus, although MEK1 and MEK2 can substitute for each other, a minimum amount of MEK is critical for placenta development and embryo survival. PMID- 26814234 TI - Cortical Venous Filling on Dynamic Computed Tomographic Angiography: A Novel Predictor of Clinical Outcome in Patients With Acute Middle Cerebral Artery Stroke. AB - BACKGROUND AND PURPOSE: Venous flow in the downstream territory of an occluded artery may influence patient prognosis after ischemic stroke. Our aim was to study cortical venous filling (CVF) in a time-resolved manner with dynamic computed tomographic angiography and to assess the relationship with clinical outcome. METHODS: Patients with a proximal middle cerebral artery occlusion underwent noncontrast CT and whole-brain CT perfusion/dynamic CT angiography within 9 hours after stroke-onset. We defined poor outcome as a modified Rankin Scale score of >=3. Association between the extent and velocity of CVF and poor outcome at 3 months was analyzed with Poisson-regression. Prognostic value of optimal CVF (maximum opacification of cortical veins) in addition to age, stroke severity, treatment, Alberta Stroke Program Early CT score, cerebral blood flow, and collateral status was assessed with logistic regression and summarized with the area under the curve. RESULTS: Eighty-eight patients were included, with a mean age of 67 years. By combining the extent and velocity of optimal CVF, we observed a decreased risk of poor outcome in patients with good and fast optimal CVF, risk ratio of 0.5 (95% confidence interval, 0.3-0.7). Extent and velocity of optimal CVF had additional prognostic value (area under the curve, 0.88; 95% confidence interval, 0.77-0.98; P<0.02) compared with a model without CVF information. CONCLUSIONS: The combination of extent and velocity of optimal CVF, as assessed with dynamic CT angiography, is useful to identify patients with acute middle cerebral artery stroke at higher risk of poor clinical outcome at 3 month follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl/trialreg and http://www.clinicaltrials.gov. Unique identifier: NTR1804 and NCT00880113, respectively. PMID- 26814236 TI - StrokeNet Takes Off: National Institute of Neurological Disorders and Stroke Organizational Update. PMID- 26814235 TI - Prognostic Significance of Hyperglycemia in Acute Intracerebral Hemorrhage: The INTERACT2 Study. AB - BACKGROUND AND PURPOSE: We aimed to determine associations of baseline blood glucose and diabetes mellitus with clinical outcomes in participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). METHODS: INTERACT2 was an international prospective, open, blinded end point, randomized controlled trial of 2839 patients with spontaneous intracerebral hemorrhage (<6 hours) and elevated systolic blood pressure randomly assigned to intensive (target systolic blood pressure <140 mm Hg) or guideline based (systolic blood pressure <180 mm Hg) BP management. Associations of hyperglycemia at presentation (>6.5 mmol/L) and combined and separate poor outcomes of death and major disability (scores of 3-6, 3-5, and 6, respectively, on the modified Rankin scale) at 90 days were determined in logistic regression models. RESULTS: In 2653 patients with available data, there were 1348 (61%) with hyperglycemia and 292 (11%) with diabetes mellitus. Associations of baseline blood glucose and poor outcome were strong and near continuous. After adjustment for baseline variables, the highest fourth (7.9-25.0 mmol/L) of blood glucose was significantly associated with combined poor outcome (adjusted odds ratio 1.35, 95% confidence interval 1.01-1.80; P trend 0.015). Diabetes mellitus also predicted poor outcome (adjusted odds ratio 1.46, 95% confidence interval 1.05 2.02; P=0.023), though more important for residual disability than death on separate analysis. CONCLUSIONS: Hyperglycemia and diabetes mellitus are independent predictors of poor outcome in patients with predominantly mild to moderate severity of intracerebral hemorrhage. These data support guideline recommendations for good glycemic control in patients with intracerebral hemorrhage. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079. PMID- 26814237 TI - Attitudes Toward Acupuncture Among Pain Fellowship Directors. AB - OBJECTIVES: The purpose of this survey was to evaluate attitudes toward acupuncture among pain medicine fellowship directors. Additional goals were to assess the availability of acupuncture at academic medical centers and ascertain the inclusion of this modality in fellowship curricula. METHODS: Electronic and paper surveys were distributed to the 97 American College of Graduate Medical Education pain medicine fellowship directors during January and February, 2014. Directors were queried about their referral patterns to acupuncture, as well as their perceptions of the utility of acupuncture for common pain conditions. They were asked about the availability of acupuncture at their institution, and whether acupuncture was included in the fellowship curriculum. RESULTS: Sixty seven percent of fellowship directors (65/97) completed the questionnaire. A majority of directors (83%) reported acupuncture is available to patients at their institution, and reported that acupuncture is a modality that they discuss with patients when creating a treatment plan for chronic pain (72%). The majority of programs include acupuncture as part of didactic (63%) and clinical (52%) education. Time constraints, lack of qualified teaching personnel, and cost to patients were cited as barriers to inclusion. The majority of fellowship directors considered acupuncture a safe and worthwhile option for common pain conditions. CONCLUSION: Results from this survey indicate that acupuncture is widely available to patients at academic medical centers, integrated into many pain fellowship curricula, and considered a useful modality by physician leaders in the field of pain medicine. This sentiment, paired with the flexibility of national guidelines for pain fellowship curricula, suggests a trend toward greater inclusion of this modality in academic medicine. PMID- 26814238 TI - The Treatment of Longstanding Complex Regional Pain Syndrome with Oral Steroids. AB - OBJECTIVE: Evaluate the effectiveness of oral steroids in relieving pain in patients with Complex Regional Pain Syndrome (CRPS) of more than 3 months duration. DESIGN: Service evaluation/Open label uncontrolled trial. SETTING: Two pain outpatient clinics specialized in CRPS diagnosis and treatment in the period 2009-2012. SUBJECTS: Thirty-one patients diagnosed with CRPS with the Budapest criteria in two specialized centers, with a disease duration of more than 3 months and not responsive to standard treatment were included. METHODS: Patients were treated with oral prednisolone in both centers [100 mg daily tapered by 25 mg every 4 days to zero (Sigma1g) at center 1 (C1) and 60 mg daily for 2 weeks lowered 20 mg every 4 days to zero (Sigma1.06g) at center 2 (C2)]. The average pain intensity was recorded by patients using a numeric rating scale before the treatment start, and 6 weeks after treatment onset (treatment duration was respectively 16 days and 22 days at the two centers). RESULTS: Overall the authors observed no significant reduction in the average pain intensity (P = 0.059), but 2 patients had a consistent reduction in pain intensity with return to baseline pain levels 9 weeks after treatment onset, and 1 patient had ongoing stable pain relief of >50%. CONCLUSIONS: This study provides indications that the efficacy of oral corticosteroids is limited in treating CRPS of more than 3 months duration who did not respond to previous treatment. Randomized controlled studies (with enriched designs), or single subject designs would be required to identify the possible existence of a patient subgroup with a specific disease profile that may benefit from a steroid treatment. PMID- 26814239 TI - Differences in Mexican Americans' Prevalence of Chronic Pain and Co-Occurring Analgesic Medication and Substance Use Relative to Non-Hispanic White and Black Americans: Results from NHANES 1999-2004. AB - OBJECTIVE: Little is known about the burgeoning Mexican American (MA) population's pain experience. METHODS: Using 1999-2004 National Health and Nutrition Examination Survey (NHANES) data, prevalence of chronic pain, analgesic medication use, and substance use were examined among MA, non-Hispanic White (NHW), and non-Hispanic Black (NHB) respondents. Logistic and linear regression models examined racial/ethnic differences in: 1) chronic pain prevalence among all respondents, 2) location and number of pain sites among respondents with chronic pain, and 3) analgesic medication and substance use among respondents with chronic pain. RESULTS: Compared to NHWs and NHBs, MAs were less likely to report any chronic pain. Among respondents with chronic pain, MAs had higher odds of reporting headache, abdominal pain, and a greater number of pain sites than NHWs. Compared to NHWs, MAs with chronic pain had lower odds of reporting past month analgesic medication and COX-2 inhibitor use. MAs with chronic pain had lower odds of being a current cigarette smoker and heavy alcohol drinker but had similar street drug/cocaine use relative to NHWs. CONCLUSIONS: Results suggest that: 1) MAs are less likely to develop chronic pain than NHWs, 2) MAs with chronic pain report greater headache and abdominal pain than NHWs, and 3) MAs with chronic pain are less likely to use analgesic medications and other substances compared to NHWs. These results suggest that providers should consider taking extra time to discuss analgesic medications with MAs. Future investigations should examine reasons underlying these racial/ethnic differences in chronic pain, as well as differences in the use of other substances, such as marijuana. PMID- 26814240 TI - Intranasal Abuse Potential, Pharmacokinetics, and Safety of Once-Daily, Single Entity, Extended-Release Hydrocodone (HYD) in Recreational Opioid Users. AB - OBJECTIVES: A once-daily, extended-release hydrocodone bitartrate tablet with abuse-deterrent properties (Hysingla ER(r) [HYD]) is available for the treatment of chronic pain in appropriate patients. This study evaluated the intranasal abuse potential and pharmacokinetics of HYD coarse and fine particles vs hydrocodone powder or placebo. DESIGN: Single-center, double-blind, positive- and placebo-controlled, randomized, four-treatment crossover study. SUBJECTS: Healthy adult, nondependent, recreational opioid users with a history of intranasal abuse. METHODS: During four treatment periods, subjects (N = 31) received hydrocodone powder 60 mg, HYD coarse particles 60 mg, HYD fine particles 60 mg, or placebo, with five-to-seven-day washouts between treatments. Measures over 36 hours postdose included drug-liking and willingness to take drug again, assessed using visual analog scales (VASs), pupillometry, intranasal irritation, and pharmacokinetics. RESULTS: Insufflation of both HYD coarse and fine particles led to lower "At this Moment" Drug Liking VAS peak values compared with hydrocodone powder, but higher values compared with placebo (P < 0.001 for all comparisons). Similar results were observed for Overall Drug Liking VAS, Take Drug Again VAS, and Subjective Drug Value. Compared with hydrocodone, insufflation of HYD particles led to reduced miosis and increased nasal irritation. Mean hydrocodone Cmax following insufflation of HYD coarse particles, HYD fine particles, and hydrocodone powder was 27.5, 36.5, and 105.8 ng/mL, respectively; median Tmax was >=2-fold longer with either HYD particle size than hydrocodone powder; and (Cmax/Tmax) was 9.5, 13.4, and 82.0 ng/mL/h, respectively. Safety was consistent with that of opioid agonists. CONCLUSIONS: HYD demonstrated reduced intranasal abuse potential compared with hydrocodone powder. PMID- 26814241 TI - Local Injection of Methylcobalamin Combined with Lidocaine for Acute Herpetic Neuralgia. AB - OBJECTIVE: To determine the efficacy of methylcobalamin combined with lidocaine for acute herpetic neuralgia. DESIGN: Randomized controlled trial with longitudinal analysis. SUBJECTS: The authors recruited 204 patients (>50 years) with T5-10 dermatomal acute herpetic neuralgia with rash onset within 7 days. Patients were divided into two groups based on the time of onset: immediate-early (IE, 1-3 days) and early stage (ES, 4-7 days) groups and then subdivided randomly into control (IE-Ctl, ES-Ctl) and treatment (IE-Tr, ES-Tr) groups. METHODS: Control groups received intramuscular methylcobalamin in addition to local lidocaine injection, while treatment groups received local methylcobalamin combined with lidocaine injection for 14 days. Treatment efficacy was assessed based on rash healing time, alteration in pain intensity, and interference with quality of life. Multilevel mixed modeling and survival analysis were employed to examine treatment responses. RESULTS: There was no significant difference in the rash healing time between IE and ES. The mean pain scores in IE-Tr (2.4 +/- 0.7) and ES-Tr (1.3 +/- 0.7) decreased significantly compared with those in the control groups. The median satisfactory response time was 6 days in ES-Tr and 11 days in IE-Tr. The benefit ratio for ES-Tr versus IE-Tr was 14.94. The subjects in IE-Tr and ES-Tr had higher quality of life scores (81.2 +/- 6.9 vs 88.3 +/- 8.6, respectively) than those in the control groups. The incidence of postherpetic neuralgia was 1.1% at 3 months. CONCLUSIONS: Local methylcobalamin combined with lidocaine, optimally administered within 4-7 days of onset, may be an effective therapeutic option for acute herpetic neuralgia. PMID- 26814242 TI - At Completion of a Multidisciplinary Treatment Program, Are Psychophysical Variables Associated with a VAS Improvement of 30% or More, a Minimal Clinically Important Difference, or an Absolute VAS Score Improvement of 1.5 cm or More? AB - OBJECTIVES: Objectives were to determine at completion of a multidisciplinary pain program: 1) what percentage of chronic low back pain (CLBP) patients had improved at 30% or more (minimal clinically important difference [MCID]) and by 1.5 cm or more (minimal important change [MIC]) on the visual analog scale (VAS) and 2) whether that improvement is associated with pain matching (PM), pain threshold (PTRE), and pain tolerance (PTOL) improvements. METHODS: One hundred and six CLBP patients had admission and discharge scores for VAS, PM, PTRE, and PTOL. Improvement was determined by absolute, MCID, and MIC VAS improvement. Logistic regression analysis controlling for age, gender, race, education, psychoactive substance dependence, and depression was utilized to develop models for the dependent variables of improvement of overall VAS; of MCID of 50% or more; and of MIC with PM, PTOL, and PTRE as independent variables. RESULTS: Thirty-two percent and 35% of the CLBP patients were at MCID and MIC, respectively, at discharge (68% and 65% not at MCID and MIC, respectively), and 54.7% were improved overall. Of the improved patients, 59% were at MCID and 63.7% at MIC. PM was associated with overall VAS improvement, while PTRE and PM were associated with MCID improvement. MIC and 50% or above models could not be estimated. LIMITATIONS: The VAS was treated as a ratio scale. CONCLUSIONS: A significant percentage of CLBP patients were at MCID and at MIC at completion of multidisciplinary treatment. PM was associated with overall VAS improvement, while PTRE and PM were associated with MCID. PMID- 26814243 TI - Expect the Un-Expected: Marked Urinary and Erectile Dysfunction with Short-Term Tramadol Use! PMID- 26814244 TI - Early Diagnostic Value of 18F-FDG PET/CT in Spontaneous Spondylodiscitis. PMID- 26814245 TI - Off-Label, Low-Dose Naltrexone for Refractory Painful Diabetic Neuropathy. PMID- 26814246 TI - Buprenorphine, Clonidine, Dexamethasone, and Ropivacaine for Interscalene Nerve Blockade: A Prospective, Randomized, Blinded, Ropivacaine Dose-Response Study. AB - OBJECTIVE: This study investigated interscalene block for shoulder arthroplasty with various ropivacaine concentrations in the presence of clonidine, dexamethasone, and buprenorphine. The goal was prolonged analgesia with minimal motor blockade. DESIGN: Prospective, double-blind, randomized controlled trial. SETTING: University-affiliated orthopedic hospital. METHODS: Patients (20/group) received acetaminophen, ketorolac, pregabalin, opioids, and "Control"; interscalene block, 0.375% ropivacaine, intravenous additives (buprenorphine, clonidine, dexamethasone); "High Dose"; 0.375% ropivacaine, perineural additives; "Medium Dose"; 0.2% ropivacaine, perineural additives; and "Low Dose"; 0.1% ropivacaine, perineural additives. RESULTS: Pain with movement at 24 hours was 4.9 +/- 2.5 (mean +/- standard deviation [SD]) (Control), 4.5 +/- 3.0 (High Dose), 3.4 +/- 1.8 (Medium Dose), 4.2 +/- 2.4 (Low Dose). The difference between Medium Dose and Control was -1.5 (95% CI: -2.9, -0.1) (P = 0.040). Median time until need for opioids was 16.1 hours (Control) vs 23.7 hours (High Dose); hazard ratio 0.37 [95% CI: 0.17, 0.79]. High Dose had less pain with movement the morning after surgery, vs Control; 2.9 +/- 2.5 vs 4.9 +/- 2.7; P = 0.027. Pain with movement in the Post-Anesthesia Care Unit was higher in Low Dose, vs Control; 0.9 +/- 1.4 vs 0 +/- 0, P = 0.009. Low Dose had superior hand strength in the Post-Anesthesia Care Unit (mean +/- SD of pre-operative strength: 44.0 +/- 20.3%) compared to Control (27.5 +/- 24.5%) (P = 0.031). CONCLUSIONS: For maximum pain reduction, combining perineural additives with ropivacaine 0.375% or 0.2% is suggested. To minimize motor blockade, perineural additives can be combined with ropivacaine, 0.1%. PMID- 26814247 TI - Perforator-Guided Drug Injection in the Treatment of Abdominal Wall Pain. AB - BACKGROUND: Pain from the abdominal wall can be caused by nerve entrapment, a condition called abdominal cutaneous nerve entrapment syndrome (ACNES). As an alternative to surgery, ACNES may be treated with injection of local anesthetics, corticosteroids, or botulinum toxin at the point of maximal pain. METHOD: The point of maximal pain was marked on the abdominal skin. Using color Doppler ultrasound, the corresponding exit point of perforating blood vessels through the anterior fascia of the rectus abdominis muscle was identified. Ultrasound-guided injection of botulinum toxin in close proximity to the perforator's exit point was performed below and above the muscle fascia. RESULTS: The technique was used from 2008 to 2014 on 15 patients in 46 sessions with a total of 128 injections without complications. The injection technique provided safe and accurate administration of the drug in proximity to the affected cutaneous nerves. The effect of botulinum toxin on ACNES is beyond the scope of this article. CONCLUSION: Perforator-guided injection enables precise drug administration at the location of nerve entrapment in ACNES in contrast to blind injections. PMID- 26814248 TI - Contact Heat Evoked Potentials (CHEPs) in Patients with Mild-Moderate Alzheimer's Disease and Matched Control--A Pilot Study. AB - OBJECTIVE: Clinical studies have found that patients with Alzheimer's disease report pain of less intensity and with a lower affective response, which has been thought to be due to altered pain processing. The authors wished to examine the cerebral processing of non-painful and painful stimuli using somatosensory evoked potentials and contact heat evoked potentials in patients with Alzheimer's disease and in healthy elderly controls. DESIGN: Case-control study SETTING AND SUBJECTS: Twenty outpatients with mild-moderate Alzheimer's disease and in 17 age and gender-matched healthy controls were included METHOD: Contact heat evoked potentials and somatosensory evoked potentials were recorded in all subjects. Furthermore, warmth detection threshold and heat pain threshold were assessed. Patients and controls also rated quality and intensity of the stimuli. RESULTS: The authors found no difference on contact heat evoked potential amplitude (P = 0.59) or latency of N2 or P2 wave (P = 0.62 and P = 0.75, respectively) between patients and controls. In addition, there was no difference in regard to pain intensity scores or pain quality. The patients and controls had similar warmth detection threshold and heat pain threshold. Somatosensory evoked potentials, amplitude, and latency were within normal range and similar for the two groups. CONCLUSIONS: The findings suggest that the processing of non-painful and painful stimuli is preserved in patients with mild to moderate Alzheimer's disease. PMID- 26814249 TI - C-Arm Fluoroscope Angle Settings for Fluoroscopically Guided Lumbar Transforaminal Epidural Injections. AB - BACKGROUND DATA: Minimizing fluoroscopy time in spine interventions is critical for time of procedure as well as radiation safety of the patient and medical personnel. Specific fluoroscopy angle settings for fluoroscopically guided L4-S1 transforaminal epidural injections (TFEIs) have not been described. OBJECTIVES: To describe the most common encountered settings for the C-arm fluoroscope angles for fluoroscopically guided L4-S1 (TFEI). METHODS: Each subject was placed in prone position on a flat fluoroscopy table without utilizing any device to alter innate lumbar spine curvature. The data from 246 consecutive patients at their first encounter in the fluoroscopy suite for a single level subpedicular lumbosacral TFEI was retrospectively analyzed. Most procedures occurred at the L4 5, L5-S1, and S1 levels (227 subjects). The C-arm angles including the oblique, cephalad/caudal were recorded for each subject upon observing final needle positioning for successful completion of the procedure according to ISIS Guidelines. RESULTS: For the L4-5 level, 71% of cases had oblique angle of 30 degrees +/-5 degrees and 94% of cases had neutral cephalad/caudal tilt (0 degrees +/-5 degrees ) observed. For the L5-S1, 72% of cases had oblique angle of 30 degrees +/-5 degrees and 62% of cases had cephalad tilt angle of 15 degrees +/-5 degrees observed. For the S1 level, 73% of cases had oblique angle of 5 degrees +/-5 degrees and 69% of cases had cephalad tilt angle of 15 degrees +/-5 degrees observed. DISCUSSION/CONCLUSION: This retrospective descriptive study suggests fluoroscope angles for L4-S1 TFEI as a starting point before fine tuning views accounting for individual anatomy. Angles suggested for each level (oblique/cephalad tilt angles) are as follows: L4-5 (30/0 degrees ), L5-S1 (30/15 degrees ), and S1 (5/15 degrees ). Prospective studies using these guidelines would need to be undertaken to prove reproducibility between interventionalists, time efficiency, and radiation exposure reduction. PMID- 26814251 TI - The Effects of Local Anesthesia Administration on Pain Experience During Interventional Spine Procedures: A Prospective Controlled Trial. AB - OBJECTIVE: It has been postulated that local anesthetic administration may be the most painful part of interventional spine procedures. Despite this, there is a lack of evidence supporting the commonly used traditional technique of anesthetic delivery as part of these procedures. This study tested three hypotheses: 1) alternative method of local anesthesia injection is superior to the traditional method; 2) using the traditional method of injection is not superior to using no local anesthetic; and 3) treatment needle size, anesthetic injection technique, and sedation are associated with pain experienced during procedures. DESIGN: Prospective, multicenter clinical trial of 127 participants who underwent elective bilateral symmetric interventional spine procedures in outpatient spine clinics. METHODS: Primary outcomes were pain scores during and after procedures to examine the influence of anesthetic injection method and treatment needle gauge on pain experience using linear mixed model regression analysis. A post-hoc comparison of estimated marginal mean pain scores was completed on both anesthetic injection method and treatment needle gauge. CONCLUSIONS: The alternative method was superior (P < 0.05) to the traditional method on post procedural pain scores. Injecting local anesthetic with the traditional or alternative method was not superior to using no local anesthetic. Treatment needle size, pain at one inch of treatment needle insertion, and baseline pain were all significantly (P < 0.05) associated with overall procedural pain. Further studies are needed optimize and justify local anesthetic injections for these procedures. PMID- 26814250 TI - Minority Aging and Endogenous Pain Facilitatory Processes. AB - OBJECTIVE: The aim of the current study was to examine the relationships among age, ethnicity, and endogenous pain facilitation using temporal summation (TS) responses to mechanical and heat stimuli. DESIGN: The present study assessed hyperalgesia and pain facilitation to thermal and mechanical stimuli at the knee and distal sites in 98 pain-free men and women. Participants were drawn from two ethnic groups [African-American (AA) and non-Hispanic white (NHW)] and two age groups (19-35 and 45-85). RESULTS: Significant main effects of ethnicity were demonstrated for both mechanical and heat modalities (all P's <= 0.05), suggesting that AA participants, relative to NHW counterparts, demonstrated enhanced hyperalgesia. Age differences (older > younger) in hyperalgesia were found in mechanical pain ratings only. Results indicated that mechanical pain ratings significantly increased from first to maximal pain as a function of both age group and ethnicity (all P's <= 0.05), and a significant ethnicity by age interaction for TS of mechanical pain was found at the forearm (P < 0.05) and trended toward significance at the knee (P = 0.071). Post-hoc tests suggested that results were primarily driven by the older AA participants, who demonstrated the greatest mechanical TS. Additionally, evidence of differences in heat TS due to both ethnicity alone (all P's <= 0.05) and minority aging was also found. CONCLUSIONS: This study provides evidence suggesting that older AAs demonstrate enhanced pain facilitatory processes, which is important because this group may be at increased risk for development of chronic pain. These results underscore the necessity of testing pain modulatory mechanisms when addressing questions related to pain perception and minority aging. PMID- 26814252 TI - Local and Widespread Hyperalgesia After Isolated Tibial Shaft Fractures Treated with Intramedullary Nailing. AB - OBJECTIVES: Knee pain is accepted as a common complication to intramedullary nailing of tibial fractures. However, no studies have systematically studied the pain sequel following tibial fractures. The objective of this study was to assess pain and hyperalgesia from 6 weeks to 12 months postoperatively after intramedullary nailing of tibial shaft fracture. METHODS: A total of 39 patients were included in this 12-month follow-up study. After 6 weeks, 3, 6, and 12 months postoperatively the pain intensity was measured on a visual analog scale (VAS) and the pressure pain sensitivity was assessed bilaterally by pain pressure thresholds (PPTs). RESULTS: The mean age at the time of fracture was 42.9 years. Twelve months after surgery, the pain intensity for worst pain during the last 24 hours was 1.8 +/- 2.7 cm. The PPTs progressively increased from 6 weeks after surgery to 12 months postoperatively for all PPT sites except for the forearm (P < 0.012). Moreover, the PPTs on the leg were generally reduced on the injured side compared with the non-injured side (P < 0.04). CONCLUSIONS: This study suggests that localized, distal, and bilateral hyperalgesia are common following an isolated tibial shaft fracture treated with intramedullary nailing, although no widespread (extrasegmental) hyperalgesia was detected. Such observations may be important for developing the most adequate rehabilitation procedure following a tibial fracture. PMID- 26814253 TI - Impaired Conditioned Pain Modulation in Young Female Adults with Long-Standing Patellofemoral Pain: A Single Blinded Cross-Sectional Study. AB - OBJECTIVE: Patellofemoral pain (PFP) is common among young individuals. Female adolescents with PFP present typically with localized mechanical hyperalgesia around the knee, but the effect of central pain mechanisms are unknown. This study aimed to compare temporal summation of pain, conditioned pain modulation (CPM), and widespread hyperalgesia in young female adults with PFP and age matched pain-free controls. DESIGN: Cross-sectional study. SETTING AND SUBJECTS: Twenty young female adults (19-21 years old) with long-standing PFP were compared with 20 pain-free controls from the same population-based cohort. METHODS: Cuff algometry was used to assess the pain detection threshold. Temporal summation of pain was assessed by recording the pain intensity on a visual analog scale during repeated cuff pressure stimulations at pain tolerance intensity on the lower leg. CPM was recorded as an increase in the cuff pain detection threshold in response to experimental conditioning pain imposed on the contralateral arm. Handheld pressure algometry was used to assess pressure pain thresholds (PPTs) on the knee, shin, and forearm. The examiner was blinded to the type of subject assessed. RESULTS: Compared with pain-free controls, young females with PFP showed no decrease in cuff pain thresholds (P < 0.40) or facilitated temporal summation (P < 0.15) but had a lower CPM response (P < 0.04) and lower PPTs (P < 0.005). CONCLUSIONS: Young female adults with long-standing PFP demonstrated impaired CPM. This is important because PFP, a peripheral pathology, might have important central components that need to be studied in order to understand its extent and therapeutic implications. PMID- 26814254 TI - Effectiveness and Factors Associated with Epidural Decompression and Adhesiolysis Using a Balloon-Inflatable Catheter in Chronic Lumbar Spinal Stenosis: 1-Year Follow-Up. AB - OBJECTIVES: This study aimed to investigate the efficacy of the combined balloon decompression with a balloon-inflatable catheter (ZiNeu) in addition to conventional epidural adhesiolysis, and to identify factors that predict patient responses. STUDY DESIGN: An institutional single-armed prospective observational study. SUBJECTS: Chronic refractory lumbar spinal stenosis. METHODS: This study was performed in 61 patients with spinal stenosis who suffered from chronic (at least 3 months) lumbar radicular pain with or without lower back pain. Patients had failed to maintain improvement for more than 1 month with conventional epidural injection. The numeric rating scale (NRS) and Oswestry disability index (ODI) were each measured at 1, 3, 6, and 12 months after percutaneous epidural adhesiolysis and balloon decompression with a ZiNeu catheter. RESULTS: The percentage of successful responders was 72.1%, 60.7%, 57.4%, and 36.1% of patients at 1, 3, 6, and 12 months, respectively. A single combined treatment of percutaneous epidural adhesiolysis and balloon decompression with a ZiNeu catheter provided sufficient pain relief and functional improvement in patients with chronic refractory lumbar spinal stenosis, and the improvement was maintained for 12 months (P < 0.001). Multivariate logistic regression analysis showed that absence of diabetes independently predicted successful response at 12 months after percutaneous epidural decompression and adhesiolysis with the balloon catheter (Odds ratio = 0.080; 95% confidence interval = 0.009-0.676; P = 0.020). CONCLUSIONS: The combined epidural adhesiolysis and balloon decompression with a ZiNeu catheter led to significant pain relief and functional improvement in a subset of patients with refractory spinal stenosis. PMID- 26814255 TI - Prevalence and Time Course of Post-Stroke Pain: A Multicenter Prospective Hospital-Based Study. AB - OBJECTIVE: Pain prevalence data for patients at various stages after stroke. DESIGN: Repeated cross-sectional, observational epidemiological study. SETTING: Hospital-based multicenter study. SUBJECTS: Four hundred forty-three prospectively enrolled stroke survivors. METHODS: All patients underwent bedside clinical examination. The different types of post-stroke pain (central post stroke pain, musculoskeletal pains, shoulder pain, spasticity-related pain, and headache) were diagnosed with widely accepted criteria during the acute, subacute, and chronic stroke stages. Differences among the three stages were analyzed with chi(2)-tests. RESULTS: The mean overall prevalence of pain was 29.56% (14.06% in the acute, 42.73% in the subacute, and 31.90% in the chronic post-stroke stage). Time course differed significantly according to the various pain types (P < 0.001). The prevalence of musculoskeletal and shoulder pain was higher in the subacute and chronic than in the acute stages after stroke; the prevalence of spasticity-related pain peaked in the chronic stage. Conversely, headache manifested in the acute post-stroke stage. The prevalence of central post-stroke pain was higher in the subacute and chronic than in the acute post stroke stage. Fewer than 25% of the patients with central post-stroke pain received drug treatment. CONCLUSIONS: Pain after stroke is more frequent in the subacute and chronic phase than in the acute phase, but it is still largely undertreated. PMID- 26814257 TI - Intrathecal Hydromorphone and Bupivacaine Combination Therapy for Post Laminectomy Syndrome Optimized with Patient-Activated Bolus Device. AB - BACKGROUND: Intrathecal (IT) pumps have become a valuable tool in managing intractable non-cancer pain. The purpose of this study was to evaluate the efficacy of using a rigorous treatment algorithm for trialing and implanting IT pumps with hydromorphone and bupivacaine in managing a more homogeneous population of post-laminectomy syndrome or failed back surgery syndrome (FBSS) patients. METHODS: This is a retrospective analysis of FBSS patients with chronic intractable back pain implanted with IT pumps delivering hydromorphone and bupivacaine. RESULTS: A cohort of 57 (26 males, 31 females) consecutively implanted FBSS patients was analyzed. The average age at implant was 65.4 years. Average pain scores were 8.4 +/- 0.2 (pre-implant), 4.9 +/- 0.4 (6 months), 5.2 +/- 0.5 (12 months), and 4.3 +/- 0.5 (24 months). Average oral opioid doses in morphine equivalents were 56 +/- 10 mg/day (pre-implant), 12.0 +/- 3.5 mg/day (12 months), 15 +/- 6 mg/day (24 months). Average IT hydromorphone doses were 79 +/- 6.8 mcg/day (at implant), 184 +/- 22 mcg/day (6 months), 329 +/- 48 mcg/day (12 months), and 487 +/- 80 mcg (24 months). IT hydromorphone dose escalation from baseline was 133% (6 months vs baseline), 78% (12 months vs 6 months), and 48% from 12 months to 24 months. Average IT bupivacaine doses were 5.8 +/- 0.3 mg/day (implant), 9.5 +/- 0.6 mg/day (6 months), 12.2 +/- 0.7 mg/day (12 months), and 12.6 +/- 0.9 mg/day (24 months). CONCLUSION: IT hydromorphone and bupivacaine are effective in treating chronic pain of FBSS, as demonstrated by the reduction of pain intensity and oral opioid consumption. However, an IT dose escalation phenomenon was observed, although at a reduced rate compared with what had been previously reported in the literature. It is possible that the local anesthetic combination delivered via a patient-activaed bolus device is an important factor. Despite demonstrating effectiveness, the clinical utility of myPTM-optimized IT therapy remains limited by a lack of prospective, placebo-controlled trials and comparative effectiveness research. PMID- 26814256 TI - A Randomized, Double-Blind, Double-Dummy Study to Evaluate the Intranasal Human Abuse Potential and Pharmacokinetics of a Novel Extended-Release Abuse-Deterrent Formulation of Oxycodone. AB - OBJECTIVE: Evaluate the human abuse potential (HAP) of an experimental, microsphere-in-capsule formulation of extended-release oxycodone (oxycodone DETERx(r)) (herein "DETERx"). DESIGN: Randomized, double-blind, double-dummy, positive- and placebo-controlled, single-dose, four-phase, four-treatment, crossover study. SETTING: Clinical research site. SUBJECTS: There were 39 qualifying subjects (72% male, 85% white, mean age of 27 years) with 36 completing all four Double-blind Treatment Periods. METHODS: The four phases encompassed: 1) Screening; 2) Drug Discrimination; 3) Double-blind Treatment; and 4) Follow-up. Drug Discrimination tests ensured that subjects could distinguish placebo from opioid. The four Double-blind Treatments compared DETERx administered as either a crushed intranasal (IN) or an intact oral (PO) preparation-with immediate-release oxycodone IN (OXY-IR IN) and with an intact IN and PO placebo DETERx control. RESULTS: For primary pharmacokinetic (PK) assessments, abuse quotient (Cmax/Tmax) was lower with DETERx IN than DETERx PO; both treatments were substantially lower than OXY-IR IN (6.24, 8.60, and 69.6 ng/mL/h, respectively). For drug liking, the primary subjective pharmacodynamic (PD) endpoint, both DETERx IN and DETERx PO produced significantly lower scores than OXY-IR IN (P <= 0.0001 for each); DETERx IN was less liked than DETERx PO (P <= 0.05), mirroring the PK relationships. Objectively assessed pupillometry corroborated the more rapid and significantly greater effect of OXY-IR IN than either DETERx IN or DETERx PO (P <= 0.007 for each). Overall safety profiles of DETERx and OXY-IR were comparable and both were well tolerated. CONCLUSIONS: Pharmacokinetic and pharmacodynamic outcomes suggest that DETERx IN has relatively low HAP; continued research in larger populations is suggested. PMID- 26814260 TI - Complications of Spinal Cord Stimulation and Peripheral Nerve Stimulation Techniques: A Review of the Literature. AB - OBJECTIVE: Spinal cord and peripheral neurostimulation techniques have been practiced since 1967 for the relief of pain, and some techniques are also used for improvement in organ function. Neuromodulation has recognized complications, although very rarely do these cause long-term morbidity. The aim of this article is to present a review of complications observed in patients treated with neurostimulation techniques. METHODS: A review of the major recent publications in the literature on the subjects of spinal cord, occipital, sacral, and peripheral nerve field stimulation was conducted. RESULTS: The incidence of complications reported varies from 30% to 40% of patients affected by one or more complications. Adverse events can be subdivided into hardware-related complications and biological complications. The commonest hardware-related complication is lead migration. Other lead related complications such as failure or fracture have also been reported. Common biological complications include infection and pain over the implant. Serious biological complications such as dural puncture headache and neurological damage are rarely observed. CONCLUSIONS: Spinal cord and peripheral neurostimulation techniques are safe and reversible therapies. Hardware-related complications are more commonly observed than biological complications. Serious adverse events such as neurological damage are rare. PMID- 26814258 TI - Trunk Muscle Size and Composition Assessment in Older Adults with Chronic Low Back Pain: An Intra-Examiner and Inter-Examiner Reliability Study. AB - OBJECTIVE: To evaluate intra- and inter-examiner reliability for the assessment of relative cross-sectional area, muscle-to-fat infiltration indices, and relative muscle cross-sectional area, i.e., total cross-sectional area minus intramuscular fat, from T1-weighted magnetic resonance images obtained in older adults with chronic low back pain. DESIGN: Reliability study. SUBJECTS: n = 13 (69.3 +/- 8.2 years old) METHODS: After lumbar magnetic resonance imaging, two examiners produced relative cross-sectional area measurements of multifidi, erector spinae, psoas, and quadratus lumborum by tracing regions of interest just inside fascial borders. Pixel-intensity summaries were used to determine muscle to-fat infiltration indices; relative muscle cross-sectional area was calculated. Intraclass correlation coefficients were used to estimate intra- and inter examiner reliability; standard error of measurement was calculated. RESULTS: Intra-examiner intraclass correlation coefficient point estimates for relative cross-sectional area, muscle-to-fat infiltration indices, and relative muscle cross-sectional area were excellent for multifidi and erector spinae across levels L2-L5 (ICC = 0.77-0.99). At L3, intra-examiner reliability was excellent for relative cross-sectional area, muscle-to-fat infiltration indices, and relative muscle cross-sectional area for both psoas and quadratus lumborum (ICC = 0.81-0.99). Inter-examiner intraclass correlation coefficients ranged from poor to excellent for relative cross-sectional area, muscle-to-fat infiltration indices, and relative muscle cross-sectional area. CONCLUSIONS: Assessment of relative cross-sectional area, muscle-to-fat infiltration indices, and relative muscle cross-sectional area in older adults with chronic low back pain can be reliably determined by one examiner from T1-weighted images. Such assessments provide valuable information, as muscle-to-fat infiltration indices and relative muscle cross-sectional area indicate that a substantial amount of relative cross sectional area may be magnetic resonance-visible intramuscular fat in older adults with chronic low back pain. PMID- 26814259 TI - Analgesic Efficacy and Safety of Curcuminoids in Clinical Practice: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: Curcuminoids are natural products with potent anti-inflammatory and antioxidant properties. There have been a number of reports on the analgesic effects of curcuminoids in clinical trials, yet data have not been fully conclusive. OBJECTIVES: To provide the highest level of evidence on the efficacy of curcuminoids in patients with painful conditions through meta-analysis of data from randomized controlled trials (RCTs). METHODS: A systematic review and meta analysis was conducted using data reported by RCTs. The primary efficacy measure was pain intensity or algofunctional status. Treatment effect was summarized with standardized mean difference (SMD) calculated from differences in means of pain measures between treatment and control groups using a random-effects model. RESULTS: A total of eight RCTs met our inclusion criteria that included 606 randomized patients. Curcuminoids were found to significantly reduce pain (SMD: 0.57, 95% CI: -1.11 to -0.03, P = 0.04). This pain-relieving effect was found to be independent of administered dose and duration of treatment with curcuminoids, and was free from publication bias. Curcuminoids were safe and well tolerated in all evaluated RCTs. CONCLUSION: Curcuminoids supplements may be a safe and effective strategy to improve pain severity, by warranting further rigorously conducted studies to define the long-term efficacy and safety. PMID- 26814261 TI - Dramatic Reduction in Hydrocodone Prescriptions in an Urban Safety Net Health Care System: Has It Improved Patient Safety or Led to Increased Patient Suffering? PMID- 26814262 TI - Opioids and Coronary Heart Disease. PMID- 26814263 TI - Persistent Back Pain Due to Intercostal Schwannoma. PMID- 26814264 TI - Iron Deficiency Anemia Is Associated with Menstrual Migraine: A Case-Control Study. AB - OBJECTIVE: Association between iron deficiency anemia (IDA) and migraine, its subgroups, or tension-type headache (TTH) has not yet been shown. This study aimed to determine whether there was an association between IDA and these disorders. DESIGN: Case-control study. SETTING: Gebze Fatih General Hospital, Kocaeli, Turkey. SUBJECTS: Migraine and TTH patients, as well as healthy controls (N = 170/group), were investigated. METHODS: Descriptive statistics and multivariate logistic regression analyses were performed. Migraine and TTH groups (that included both sexes) and specific migraine subtypes (females only) were selected as dependent variables with sex, age, family history of migraine, alcohol consumption, cigarette smoking, and IDA selected as independent variables. The migraine subgroups selected were as follows: (1) pure menstrual migraine (PMM) or menstrually related migraine (MRM) and (2) migraine not associated with menses (MNAM). RESULTS: IDA was more common in patients with migraine than controls (21.7% vs 12.9%, P = 0.02). There was no association between IDA and TTH (15.9% vs 12.9%, P = 0.43). Family history of migraine (P < 0.001) and IDA (P = 0.03) were significant factors in the model of migraine. Age (P = 0.009), family history of migraine (P < 0.001), and IDA (P = 0.018) were significant factors in the model of PMM/MRM. Only family history of migraine (P < 0.001) was significant in the model of MNAM. CONCLUSIONS: Our findings indicate that IDA is significantly associated with PMM/MRM. Further research may determine whether the complex relationships between estrogen, iron metabolism, and dopamine dysfunction, and their effects on migraine, are underlying reasons for this association. PMID- 26814265 TI - Effects of Low-Dose Escherichia coli Lipopolysaccharide-Induced Endotoxemia on Morphine Pharmacokinetics in an Animal Model. AB - OBJECTIVE: Systemic inflammation may change the bioavailability and pharmacokinetics of opioids. However, there are insufficient data on morphine pharmacokinetics in mild inflammatory conditions. This study aimed to determine the pharmacokinetics of morphine during low-dose endotoxemia in rabbits. DESIGN: In two experiments (separated by a 14-day washout period), 10 rabbits received intravenous morphine at a dose of 3 mg/kg. In the second set of experiments, morphine infusion was preceded by low-dose endotoxemia induced with lipopolysaccharide (Escherichia coli 0111: B4) at a dose of 5 ug/kg. The kinetics of systemic morphine concentrations and chosen physiological parameters were measured at specific time intervals up to 6 hours after morphine administration. RESULTS: In endotoxemia, decreased elimination half-life (P = 0.017), mean residence time (P = 0.022), and volume of distribution (P = 0.037) as well as an increased elimination rate constant (P = 0.013) and total body clearance (P = 0.023) were noted. The inverse linear correlation between morphine clearance versus the percentage (%) change in body temperature and pulse rate observed under control conditions was abolished under endotoxemia. CONCLUSIONS: Low-dose endotoxemia is correlated with significant alterations in morphine pharmacokinetics in rabbits, leading to the faster elimination of the drug. CLINICAL IMPLICATIONS: These findings may have important implications in patients with low-grade inflammation and imply the need to modify morphine dosing regimens to ensure optimal analgesia. The issue warrants further experimental and clinical investigation. PMID- 26814266 TI - Contralateral Oblique View Is Superior to the Lateral View for Lumbar Epidural Access. AB - OBJECTIVE: The purpose of this study was to perform a comparative analysis of the contralateral oblique (CLO) view and the lateral view for lumbar interlaminar epidural access. DESIGN: After the epidural space was accessed, fluoroscopic images at eight different angles (antero-posterior view, multiple CLO, and lateral view) were prospectively obtained. Visualization and location of needle tip relative to bony landmarks were analyzed. The epidural location of the needle was subsequently confirmed by contrast injection and analysis in multiple views. RESULTS: Visualization of the needle tip and the relevant radiologic landmarks was superior in the CLO view. The needle tip location in the epidural space was most consistent at a CLO angle of 45 degrees . CONCLUSION: This study shows that the CLO view for lumbar interlaminar epidural access offers clear advantages over the lateral view on many clinically important grounds: the needle tip visualization is better, the important radiological landmarks are better visualized, and the needle tip when placed in the epidural space presents a more precise relationship to these landmarks. All of these differences were highly significant. Thus, when using this view, the needle may be directly placed in very close vicinity to the epidural space and true loss of resistance expected soon thereafter. In addition, this view provides the ability to plot the cranio caudad needle trajectory. The combination of these factors is likely to improve the ease and efficiency of epidural access. The crisp visualization of the final moments of epidural access could also translate to improved safety and accuracy. In light of this, it is suggested that a CLO view at 45 degrees be considered the preferred view for gauging needle depth during interlaminar lumbar epidural access. PMID- 26814268 TI - Epidemiology of Primary Headaches Among 1,876 Adolescents: A Cross-Sectional Survey. AB - BACKGROUND: The main goal of our research was to perform an epidemiological study of migraine and tension-type headache (TTH) among high school students in the Republic of Croatia. METHODS: The authors surveyed 1,876 students attending high schools in the Republic of Croatia using a self-administered 36-item questionnaire. RESULTS: Among 1,876 students who completed the questionnaire, prevalence of migraine was 12.8% (17% in women and 8.1% in men) and prevalence of TTH was 38.3% (40.6% in women and 35.7% in men). Prevalence of migraine with TTH was 2.9% (3.1% in women and 2.7% in men). The authors found a significantly greater prevalence of migraine in female than in male students (OR = 2.3), as in TTH (OR = 1.23). Compared with students with TTH, migraine sufferers were more inclined to take medications (OR = 3.29) and use health care (OR = 8.12) and were more likely to smoke (OR = 2.34). CONCLUSION: The prevalence of primary headaches in Croatia is similar to that in other countries of the world. TTH is the most common primary headache, occurring later in relation to migraine, and both types are more common in females. Teenagers who suffer from migraines are more likely to smoke in comparison to TTH. Although migraine patients visit the doctor and take medications more frequently than those with TTH, both headaches are being underdiagnosed and undertreated. PMID- 26814267 TI - Diversion and Illicit Sale of Extended Release Tapentadol in the United States. AB - OBJECTIVE: Prescription opioid analgesics are commonly prescribed for moderate to severe pain. An unintended consequence of prescribing opioid analgesics is the abuse and diversion of these medications. Tapentadol ER is a recently approved centrally acting analgesic with synergistic mechanisms of action: MU-opioid receptor agonism and inhibition of norepinephrine reuptake. We assessed the amount of diversion and related cost of obtaining tapentadol IR (Nucynta(r)) and tapentadol ER (Nucynta ER(r)) as well as other Schedule II opioid medications in street transactions in the United States using the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS(r)) System. METHODS: The Drug Diversion Program measures the number of cases opened by 260 drug diversion investigators in 49 states. StreetRx(TM) uses a crowd-sourcing Website to collect the prices paid for licit or illicit drugs. RESULTS: The population-based rates of diversion were 0.003 (tapentadol IR), 0.001 (tapentadol ER), and 1.495 (other Schedule II opioid tablets) reports per 100,000 population. The tapentadol ER rate was lower than the other Schedule II opioid tablets (P < 0.001) and tapentadol IR (P= 0.004). Diversion rates based on drug availability were 0.03 (tapentadol IR), 0.016 (tapentadol ER), and 0.172 (other Schedule II opioid tablets) per 1,000 prescriptions dispensed. The median street price per milligram was $0.18 (tapentadol IR), $0.10 (tapentadol ER), and $1.00 (other Schedule II opioid tablets). DISCUSSION: Our results indicate that tapentadol ER is rarely sold illicitly in the United States. When sold illicitly, tapentadol ER costs less than other Schedule II opioid products. PMID- 26814269 TI - Patients Presenting to the Emergency Department with Acute Pain: The Significant Role of Pain Catastrophizing and State Anxiety. AB - OBJECTIVE: Pain is one of the most common reasons for emergency department (ED) visits. Given the significant association of psychological variables and pain experience, it is critical to examine the relation of such factors with ED pain reports. This study sought to analyze the association of reported pain intensity in ED with pain catastrophizing and state anxiety. METHODS: One hundred participants presenting with a primary complaint of acute pain in an urban ED completed the study. The measures included a demographic survey with questions pertaining to pain intensity, type and duration of present pain, the Pain Catastrophizing Scale (PCS), and the State-Trait Anxiety Inventory-State Subscale (STAI-S). RESULTS: Pain intensity was significantly and positively associated with pain catastrophizing and state anxiety. Follow-up PROCESS mediation analysis revealed a significant indirect effect of pain catastrophizing on the relationship between state anxiety and pain intensity. CONCLUSIONS: The results suggest that it is important to assess the psychological distress due to anxiety and pain catastrophizing of patients presenting to EDs with acute pain. Setting appropriate brief behavioral interventions in conjunction with pharmacological interventions could improve outcomes. PMID- 26814270 TI - Enhanced RAGE Expression in the Dorsal Root Ganglion May Contribute to Neuropathic Pain Induced by Spinal Nerve Ligation in Rats. AB - OBJECTIVE: There is some evidence implicating receptor for advanced glycation end products (RAGE) signaling in the pathogenesis of neuropathic pain (NP). The objective was to investigate whether RAGE signaling in the dorsal root ganglion (DRG) might contribute to NP following peripheral nerve injury. DESIGN: Experimental study before and after spinal nerve ligation (SNL) surgery. SETTING: Caged in a controlled environment. SUBJECTS: Male Sprague-Dawley rats. METHODS: A SNL rat model of NP was used. Mechanical hyperalgesia was measured by the paw withdrawal threshold (PWT) to mechanical stimuli (1.4-15 g). Protein expressions of RAGE (immunofluorescence and western blotting), glial fibrillary acidic protein (GFAP; satellite glial cell [SGC] activation marker), IL-1beta (ELISA), TNF-alpha (ELISA), and NF-kappaB (western blotting) in the DRG were determined. RAGE signaling was inhibited by intrathecal injection of anti-RAGE antibody. RESULTS: After 7 days, SNL surgery reduced the PWT and upregulated the protein expression of RAGE, GFAP, NF-kappaB, TNF-alpha, and IL-1beta. Intrathecal injection of RAGE-neutralizing antibody attenuated the SNL-induced mechanical hyperalgesia, activation of SGCs, and upregulation of NF-kappaB, TNF-alpha, and IL-1beta in the DRG. CONCLUSION: RAGE signaling may contribute to the pain hypersensitivity observed in the rat SNL model of NP. Although the precise mechanism remains to be established, NF-kappaB, TNF-alpha, and IL-1beta likely play a role, together with the activation of SGCs. PMID- 26814271 TI - Association of Physical Fitness with Depression in Women with Fibromyalgia. AB - OBJECTIVE: The aim of this study was to examine the association between physical fitness and depressive symptoms in women with fibromyalgia (FM). We also assessed whether different fitness components present independent relationships with depressive symptoms. DESIGN: Cross-sectional study. SETTING: University facilities and FM associations. SUBJECTS: Four hundred and forty-four patients with FM according to the 1990 American College of Rheumatology criteria. METHODS: Depressive symptoms were assessed using the Beck Depression Inventory (BDI-II). Physical fitness (aerobic fitness, muscle strength, flexibility, and motor agility) was assessed using the standardized Senior Fitness Test battery and the handgrip strength test. A standardized composite score for fitness was computed and divided into quintiles. RESULTS: Overall, the fitness tests presented inverse associations with the total BDI-II score (P < 0.05). The patients in the highest fitness quintile had 8.4% lower depressive symptoms than the patients in the lowest fitness quintile (P = 0.014). The odds of severe symptoms of depression were between 3.7% and 16.9% lower for each performance unit in the back-scratch, handgrip, arm-curl, and eight-feet up-and-go tests. When all the fitness tests were simultaneously considered, the back-scratch test was the only one independently associated with the total BDI-II score (P = 0.001; R(2) = 0.023). CONCLUSIONS: Although higher physical fitness was generally associated with lower symptoms of depression in women with FM, the observed associations were somewhat weak and inconsistent, differing from those previously observed in healthy adults. Further research to determine the clinical relevance of the association between physical fitness and depression in FM is warranted. PMID- 26814272 TI - An Uncommon Cause of Posterior Knee Pain: Diagnosis and Injection for Popliteus Strain Using Ultrasonography. PMID- 26814273 TI - Re: Signs and Symptoms of Myofascial Pain: An International Survey of Pain Management Providers and Proposed Preliminary Set of Diagnostic Criteria. PMID- 26814274 TI - Response to Rathbone and Kuthmare. PMID- 26814275 TI - Successful Peripheral Neuromodulation for Phantom Limb Pain: An Update. PMID- 26814277 TI - Physiological Indices of Stress Prior to and Following Total Knee Arthroplasty Predict the Occurrence of Severe Post-Operative Pain. AB - OBJECTIVE: The severe pain and disability associated with osteoarthritis often motivate individuals to undergo arthroplastic surgery. However, a significant number of surgical patients continue to experience pain following surgery. Prior research has implicated both the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) in the sensitization of pain receptors and chronic pain conditions. This study uses a prospective, observational, cohort design to examine whether physiological stress responses before and after surgery could predict post-operative pain severity. SUBJECTS: Participants included 110 patients undergoing total knee arthroplasty. METHODS: Physiological indices of stress included the measurement of catecholamine and cortisol levels in 15-hour urine samples collected prior to and 1 month following surgery, as well as in hospital heart rate and blood pressure (before and after surgery), which were abstracted from medical records. Patients completed the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [Bellamy et al., J Orthop Rheumatol 1: , 95 (1988)] 2.5 weeks prior to surgery and at a 3 month follow-up. RESULTS: Contrary to expectations, lower stress hormone levels at baseline were related to more severe post-operative pain. Data at later time points, however, supported our hypothesis: cardiovascular tone shortly before surgery and urinary levels of epinephrine 1 month following surgery were positively related to pain severity 3 months later. CONCLUSION: Results suggest that the occurrence of post-operative pain can be predicted on the basis of stress physiology prior to and following arthroplastic surgery. PMID- 26814276 TI - Transcranial Direct Current Stimulation (tDCS) Targeting Left Dorsolateral Prefrontal Cortex Modulates Task-Induced Acute Pain in Healthy Volunteers. AB - OBJECTIVE: Current chronic pain treatments target nociception rather than affective "suffering" and its associated functional and psychiatric comorbidities. The left dorsolateral prefrontal cortex (DLPFC) has been implicated in affective, cognitive, and attentional aspects of pain and is a primary target of neuromodulation for affective disorders. Transcranial direct current stimulation (tDCS) can non-invasively modulate cortical activity. The present study tests whether anodal tDCS targeting the left DLPFC will increase tolerability of acute painful stimuli vs cathodal tDCS. METHODS: Forty tDCS-naive healthy volunteers received anodal and cathodal stimulation targeting the left DLPFC in two randomized and counterbalanced sessions. During stimulation, each participant performed cold pressor (CP) and breath holding (BH) tasks. We measured pain intensity with the Defense and Veterans Pain Rating Scale (DVPRS) before and after each task. RESULTS: Mixed ANOVA revealed no main effect of stimulation polarity for mean CP threshold, tolerance, or endurance, or mean BH time (allP > 0.27). However, DVPRS rise associated with CP was significantly smaller with anodal vs cathodal tDCS (P = 0.024). We further observed a significant tDCS polarity * stimulation order interaction (P = 0.042) on CP threshold, suggesting task sensitization. CONCLUSIONS: Although our results do not suggest that polarity of tDCS targeting the left DLPFC differentially modulates the tolerability of CP- and BH-related pain distress in healthy volunteers, there was a significant effect on DVPRS pain ratings. This contrasts with our previous findings that tDCS targeting the left dorsal anterior cingulate cortex showed a trend toward higher mean CP tolerance with cathodal vs anodal stimulation. The present results may suggest tDCS-related effects on nociception or DLPFC-mediated attention, or preferential modulation of the affective valence of pain as captured by the DVPRS. Sham-controlled clinical studies are needed. PMID- 26814278 TI - Can Pain or Hyperalgesia Be a Classically Conditioned Response in Humans? A Systematic Review and Meta-Analysis. AB - BACKGROUND: Clinical scenarios of repeated pain usually involve both nociceptive and non-nociceptive input. It is likely that associations between these stimuli are learned over time. Such learning may underlie subsequent amplification of pain, or evocation of pain in the absence of nociception. METHODS: We undertook a systematic review and meta-analysis to evaluate the evidence that allodynia or hyperalgesia can be a classically conditioned response. A sensitive search of the literature covered Medline, Embase, CINAHL, AMED, PubMed, Scopus, PsycArticles, PsycINFO, Cochrane Library, and Web of Science. Additional studies were identified by contacting experts and searching published reviews. Two reviewers independently assessed studies for inclusion, evaluated risk of bias, and extracted data. Studies were included if they aimed to elicit or amplify pain using a classical conditioning procedure in healthy, adult humans. Studies were excluded if they did not distinguish between classical conditioning and explicit verbal suggestion as learning sources, or did not use experiential learning. RESULTS: Thirteen studies, with varying risk of bias, were included. Ten studies evaluated classically conditioned hyperalgesia: nine found hyperalgesia; one did not. Pooled effects (n = 8 with full data) showed a significant pain increase after conditioning (mean difference of 7.40 [95%CI: 4.00-10.80] on a 0-100 pain scale). Three studies evaluated conditioned allodynia and found conflicting results. CONCLUSION: The existing literature suggests that classical conditioning can amplify pain. No conclusions can be drawn about whether or not classical conditioning can elicit pain. Rigorous experimental conditioning studies with nociceptive unconditioned stimuli are needed to fill this gap in knowledge. PMID- 26814279 TI - Performance of a Patient Reported Outcomes Measurement Information System (PROMIS) Short Form in Older Adults with Chronic Musculoskeletal Pain. AB - OBJECTIVE: To assess reliability, validity, and responsiveness of a 29-item short form version of the Patient Reported Outcomes Measurement Information System (PROMIS) and a novel "impact score" calculated from those measures. DESIGN: Prospective cohort study. SETTING: Rural primary care practices. SUBJECTS: Adults aged >= 55 years with chronic musculoskeletal pain, not currently receiving prescription opioids. METHODS: Subjects completed the PROMIS short form at baseline and after 3 months. Patient subsets were compared to assess reliability and responsiveness. Construct validity was tested by comparing baseline scores among patients who were or were not applying for Worker's Compensation; those with higher or lower catastrophizing scores; and those with or without recent falls. Responsiveness was assessed with mean score changes, effect sizes, and standardized response means. RESULTS: Internal consistency was good to excellent, with Cronbach's alpha between 0.81 and 0.95 for all scales. Among patients who rated their pain as stable, test-retest scores at 3 months were around 0.70 for most scales. PROMIS scores were worse among patients seeking or receiving worker's compensation, those with high catastrophizing scores, and those with recent falls. Among patients rating pain as "much less" at 3 months, absolute effect sizes for the various scales ranged from 0.24 (Depression) to 1.93 (Pain Intensity). CONCLUSIONS: Results indicate that the PROMIS short 29-item form may be useful for the study of patients with chronic musculoskeletal pain. Our findings also support use of the novel "impact score" recommended by the National Institutes of Health (NIH) Task Force on Research Standards for Chronic Low Back Pain. PMID- 26814280 TI - One Month of Oral Morphine Decreases Gray Matter Volume in the Right Amygdala of Individuals with Low Back Pain: Confirmation of Previously Reported Magnetic Resonance Imaging Results. AB - OBJECTIVE: Prolonged exposure to opioids is known to produce neuroplastic changes in animals; however, few studies have investigated the effects of short-term prescription opioid use in humans. A previous study from our laboratory demonstrated a dosage-correlated volumetric decrease in the right amygdala of participants administered oral morphine daily for 1 month. The purpose of this current study was to replicate and extend the initial findings. METHODS: Twenty one participants with chronic low back pain were enrolled in this double-blind, placebo-controlled study. Participants were randomized to receive daily morphine (n = 11) or a matched placebo (n = 10) for 1 month. High-resolution anatomical images were acquired immediately before and after the treatment administration period. Morphological gray matter changes were investigated using tensor-based morphometry, and significant regions were subsequently tested for correlation with morphine dosage. RESULTS: Decreased gray matter volume was observed in several reward- and pain-related regions in the morphine group, including the bilateral amygdala, left inferior orbitofrontal cortex, and bilateral pre supplementary motor areas. Morphine administration was also associated with significant gray matter increases in cingulate regions, including the mid cingulate, dorsal anterior cingulate, and ventral posterior cingulate. CONCLUSIONS: Many of the volumetric increases and decreases overlapped spatially with the previously reported changes. Individuals taking placebo for 1 month showed neither gray matter increases nor decreases. The results corroborate previous reports that rapid alterations occur in reward-related networks following short-term prescription opioid use. PMID- 26814281 TI - Investigating the Effects of Pulsed Radiofrequency on Dorsal Root Ganglion in Chronic Lumbar Radicular Pain Patients: Is It Not Important that We Ask the Right Question, the Right Way, on an Appropriate Sample of Patients? PMID- 26814283 TI - Intradiscal Platelet-Rich Plasma Injection for Chronic Discogenic Low Back Pain: Preliminary Results from a Prospective Trial. AB - BACKGROUND: Platelet-rich plasma (PRP) has been found to be effective for a variety of musculoskeletal conditions. The treatment of discogenic pain with PRP is under investigation. OBJECTIVE: To assess changes in pain and function in patients with discogenic low back pain after an intradiscal injection of PRP. STUDY DESIGN: Prospective trial. METHODS: Patients were diagnosed with discogenic low back pain by clinical means, imaging, and exclusion of other structures. Provocation discography was used in a minority of the patients. Patients underwent a single treatment of intradiscal injection of PRP at one or multiple levels. MAIN OUTCOME MEASURES: Patients were considered a categorical success if they achieved at least 50% improvement in the visual analog score and 30% decrease in the Oswestry Disability Index at 1, 2, and 6 months post-treatment. RESULTS: 22 patients underwent intradiscal PRP. Nine patients underwent a single level injection, ten at 2 levels, two at 3 levels, and one at 5 levels. Categorical success rates were as follows: 1 month: 3/22 = 14% (95% CI 0% to 28%), 2 months: 7/22 = 32% (95% CI 12% to 51%), 6 months: 9/19 = 47% (95% CI 25% to 70%). CONCLUSION: This trial demonstrates encouraging preliminary 6 month findings, using strict categorical success criteria, for intradiscal PRP as a treatment for presumed discogenic low back pain. Randomized placebo controlled trials are needed to further evaluate the efficacy of this treatment. PMID- 26814282 TI - Is There a Relationship Between Body Mass Index and Fluoroscopy Time During Sacroiliac Joint Injection? A Multicenter Cohort Study. AB - OBJECTIVE: To determine the relationship between BMI and fluoroscopy time during intra-articular sacroiliac joint (SIJ) injections performed for a pain indication. DESIGN: Multicenter retrospective cohort study. SETTING: Three academic, outpatient pain treatment centers. SUBJECTS: Patients who underwent fluoroscopy guided SIJ injection with encounter data regarding fluoroscopy time during the procedure and body mass index (BMI). MAIN OUTCOME MEASURE: Median and 25-75% Interquartile Range (IQR) fluoroscopy time. RESULTS: 459 SIJ injections (350 patients) were included in this study. Patients had a median age of 57 (IQR 44, 70) years, and 72% were female. The median BMI in the normal weight, overweight, and obese groups were 23 (IQR 21, 24), 27 (IQR 26, 29), and 35 (IQR 32, 40), respectively. There was no significant difference in the median fluoroscopy time recorded between these BMI classes (p = 0.45). First-time SIJ injection (p = 0.53), bilateral injection (p = 0.30), trainee involvement (p = 0.47), and new trainee involvement (trainee participation during the first 2 months of the academic year) (p = 0.85) were not associated with increased fluoroscopy time for any of the three BMI categories. CONCLUSIONS: Fluoroscopy time during sacroiliac joint injection is not increased in patients who are overweight or obese, regardless of whether a first-time sacroiliac joint injection was performed, bilateral injections were performed, a trainee was involved, or a new trainee was involved. PMID- 26814284 TI - Timeliness of Care Planning upon Initiation of Chronic Opioid Therapy for Chronic Pain. AB - BACKGROUND: Chronic opioid therapy (COT) guidelines recommend developing a COT care plan at the initiation of COT. OBJECTIVE: Assess the timeliness of care planning upon initiation of COT. DESIGN: Observational cohort study in a setting incentivizing and tracking documentation of COT care plans in electronic health records (EHRs). PARTICIPANTS: Study participants (N = 896) were aged 45 years or older, had initiated an episode of opioid use within the prior 6 months, and reported regular use of prescription analgesics when screened for a baseline interview about 3 months after an index opioid prescription MEASURES: A timely care plan was defined by an EHR documented care plan prior to or within 4 months after the index opioid prescription. RESULTS: Among COT initiators, 30% had a timely COT care plan documented in the EHR within 4 months following index prescription, while 51% had a documented COT care plan within 12 months following index prescription. Among those interviewed at 1 year follow-up (N = 735), 252 (34.2%) reported opioid use on 7 or more days in the prior 2 weeks. Less than half (45.6%) of the 252 individuals who sustained regular opioid use at 1 year had predicted at baseline that it was somewhat, very, or extremely likely they would be using opioids regularly in 1 year. CONCLUSIONS: Patients initiating COT were unlikely to have timely COT care plans. Many who sustained regular opioid use at 1 year had not anticipated using opioids long term. PMID- 26814285 TI - Improving Trainee Competency and Comfort Level with Needle Driving Using Simulation Training. AB - OBJECTIVE: To assess whether a combination of lecture and model simulation improves resident competency and comfort level with needle driving for interventional pain medicine procedures. DESIGN: Prospective, observational study. METHOD: Trainees who rotated through the University of California, Irvine, outpatient pain medicine clinic were recruited for the study. Subjects were given a brief lecture and completed a survey with questions regarding their level of comfort with interventional pain medicine procedures. This was followed by a timed trial on a training simulator where the objective was to drive a needle to the target. After the trial, the subject was then given a 30-minute practice session with the simulation model. The subject was then asked to repeat the timed trial and complete a post-simulation survey. RESULTS: All measures of the level of comfort increased significantly after subjects underwent the simulation training. In addition, subjects were able to significantly decrease their entrance time (P= 0.002), total time (P= 0.033), and vertical (P<= 0.001) and horizontal deviation (P<= 0.001) from the final target point after the simulation training. CONCLUSIONS: Our study demonstrates that simulation training may improve both trainee comfort level and competency with needle driving. After a brief lecture and a 30-minute training session with the simulator, subjective comfort measures and competency measures (more subjects were able to reach the target, vertical and horizontal deviations from the target decreased) were significantly improved. This suggests that simulation may be a helpful tool in teaching needle driving skills. PMID- 26814286 TI - Successful Management of Corneal Neuropathic Pain with Intrathecal Targeted Drug Delivery. AB - OBJECTIVE: To describe the successful treatment of refractory corneal neuropathic pain with neuromodulation techniques. DESIGN: Single case report. SETTING: Academic tertiary care center in the United States of America. SUBJECT AND METHODS: A 30-year-old woman presented with a 7-year history of refractory bilateral keratoneuralgia following laser-assisted in-situ keratomileusis (LASIK) procedure on both eyes. Having failed all conservative measures, the patient initially underwent trigeminal nerve stimulation and subsequently was implanted with an intrathecal drug delivery system (IDDS) with the catheter placed at the level C1. RESULTS: Following an initial favorable response to the trigeminal nerve stimulator, the pain became refractory to neurostimulation after a few months and the system was explanted. The patient was successfully trialed with an intrathecal catheter placed at the level of C1 delivering a combination of bupivacaine and low dose fentanyl. The patient was then implanted with an IDDS equipped with a patient-activated bolus system. The patient was very satisfied with the treatment and has had greater than 50% pain relief for over a year. CONCLUSIONS: Intrathecal delivery of bupivacaine and low dose fentanyl in the upper cervical spine can be effective in controlling refractory eye pain in properly selected patients and treatment centers. PMID- 26814287 TI - Influence of Neonatal Pain in Motor Development During Childhood. PMID- 26814288 TI - Questions Regarding "Pulsed Radiofrequency for Chronic Intractable Lumbosacral Radicular Pain: A Six-Month Cohort Study". PMID- 26814289 TI - Can a Smartphone Application Help Balance Patient Autonomy and Public Safety in Drivers Who Take Psychoactive Medications? PMID- 26814290 TI - Reply to Remarks on the Six-Month Cohort Study on PRF for Chronic Intractable Radicular Pain. PMID- 26814291 TI - An Online Survey of Patients' Experiences Since the Rescheduling of Hydrocodone: The First 100 Days. AB - OBJECTIVE: To conduct an Internet patient survey through the National Fibromyalgia & Chronic Pain Association on reactions to the first 100 days following the rescheduling of hydrocodone. METHODS: Face-valid survey questions were created with expert consensus along with repurposed questions used on previous NFMCPA surveys covering domains such as demographics and symptoms. The questionnaire was designed to be administered over the Internet. RESULTS: 6,420 responders met screening criteria and completed the survey. Most (5,181, or 82.5%) had been prescribed hydrocodone for more than 1 year. 2,296, (39.0%) reported no changes in access to hydrocodone, while the majority experienced some barriers. Of those who could no longer get hydrocodone, 1,067 (18.1%) borrowed pain medications, 1,007 (17.1%) turned to marijuana, 773 (13.1%) used alcohol, and 135 (2.3%) used illicit drugs. Most respondents had to visit their healthcare providers more often (N = 3,699, 64.2%) and 1,735 (30.3%) reported some type of issue interacting with their pharmacy. Most felt that the rescheduling was neither a fair nor appropriate solution to the abuse of hydrocodone (N = 4,938, 88.3%). For those still working, 801 (46.2%) reported that they had missed work because of the stricter regulations. 1,462 (27.2%) reported having thoughts of suicide since the rescheduling. SIGNIFICANCE: The unintended consequences for people with chronic pain that have been caused by the rescheduling effort to impede hydrocodone abuse are negatively impacting thousands. These consequences include suffering from being placed on less effective drugs, increased cost, inconvenience, and negative influence on physician-patient and pharmacist-patient relationships. PMID- 26814292 TI - The Discriminatory Ability of the Fibromyalgia Rapid Screening Tool (FiRST): An International Study in Spain and Four Latin American Countries. AB - OBJECTIVE: To assess the transcultural equivalency of the Spanish version of the Fibromyalgia Rapid Screening Tool (FiRST) and its discriminatory ability in different Latin American samples. DESIGN: Validation study. SETTING: Departments of Rheumatology in general hospitals and private centers; fibromyalgia unit in a university hospital. SUBJECTS: 350 chronic pain patients from Spain, Argentina, Mexico, Peru, and Ecuador. METHODS: The cultural relevance of the Spanish version of the FiRST was evaluated. The ability of the FiRST as a screening tool for fibromyalgia was assessed by logistic regression analysis. To determine the degree to which potential confounders, such as differences in demographics, pain, affective distress, catastrophizing, and disability, might affect the discriminatory ability, the tool was reassessed by hierarchical multivariate logistic regression. RESULTS: Slightly different versions of the FiRST were recommended for use in each Latin American subsample. The FiRST showed acceptable criterion validity and was able to discriminate between fibromyalgia and non fibromyalgia patients even after controlling for the effect of potential confounders. However, low specificities were observed in samples from Spain and Mexico. CONCLUSIONS: The Spanish version of the FiRST may be used as a screening tool for fibromyalgia in several Latin American subsamples, even in those patients with high scores on potential confounders. In Spain and Mexico, the low specificity of the FiRST suggests, however, that it would be best used to support a suspected diagnosis of fibromyalgia, rather than to exclude the diagnosis. PMID- 26814293 TI - The Incidence of Intradiscal, Intrathecal, and Intravascular Flow During the Performance of Retrodiscal (Infraneural) Approach for Lumbar Transforaminal Epidural Steroid Injections. AB - BACKGROUND: Lumbar transforaminal epidural steroid injections (TFESIs) are often used in the treatment of radicular pain. In light of safety concerns, many practitioners have proposed adopting the retrodiscal (infraneural) approach with the needle tip positioned into Kambin's triangle. With this technique, the needle may inadvertently be directed too far ventrally and enter the intervertebral disc. In addition, the risk of subarachnoid or subdural extra-arachnoid injection may be higher with this technique as well. OBJECTIVE: To determine the incidence of inadvertent intradiscal, intrathecal, and vascular injections during the performance of retrodiscal TFESI. STUDY DESIGN: Retrospective review METHODS: Retrospective review of all retrodiscal approach TFESIs performed from July 2012 to August 2014 by two of the authors (DL and SH). RESULTS: A total of 257 retrodiscal transforaminal injections were performed. There were no neurologic complications. There were no cases of discitis. Inadvertent intradiscal injections occurred in 12/257 injections, 4.7% (95% CI 2.1-7.3%). Intrathecal injections occurred in 8/257 injections, 3.1% (95% CI 0.99- 5.23%). Three were subarachnoid (SA), four were subdural extra-arachnoid (SDXA), and one was both SA and SDXA. Vascular injections occurred in 17/257, 6.6% (95% CI 3.6-9.6%). CONCLUSION: This retrospective review demonstrates that a relatively high rate of inadvertent intradiscal injections occurs in the performance of the retrodiscal approach for TFESI. This has significant implications in terms of the potential risk of disc injury induced by the needle puncture. The high incidence of intrathecal injections may also be of great concern depending upon the injectate delivered. PMID- 26814294 TI - A Randomized, Double-Blind, Placebo-Controlled, Crossover Study of the T-Type Calcium Channel Blocker ABT-639 in an Intradermal Capsaicin Experimental Pain Model in Healthy Adults. AB - OBJECTIVE: This randomized, double-blind, placebo-controlled, crossover trial evaluated the pharmacodynamic effects of a single 100-mg dose of ABT-639, a peripherally active, selective T-type Cav3.2 channel blocker, with the intradermal capsaicin pain model using pregabalin 300 mg as a positive control. SUBJECTS: Healthy adult males (aged 21 to 55 years) were randomly assigned to receive single oral doses of ABT-639, pregabalin, and placebo. METHODS: Serial measurements for area (cm2) of hyperalgesia, allodynia, and flare response were performed over a 20-minute period after each capsaicin injection at 1 and 4 hours post-dose. Capsaicin injections were administered in different arms as determined by random assignment. Serial measurements for spontaneous pain and elicited pain were performed over a 60-minute period at 1 and 4 hours post-dose using a 100-mm visual analog scale. Standard safety evaluations were performed. RESULTS: Nineteen participants were randomized and included in the analysis. No significant differences were observed between ABT-639 and placebo in spontaneous pain, elicited pain, and areas of allodynia, hyperalgesia, and flare after intradermal capsaicin injection at 1 and 4 hours post-dose. In contrast, pregabalin demonstrated significant reductions in spontaneous pain at 1 and 4 hours post-dose, and elicited pain and areas of allodynia and hyperalgesia at 4 hours post-dose compared with placebo. ABT-639 demonstrated acceptable safety and tolerability; somnolence and euphoric mood were the most commonly reported adverse events. CONCLUSIONS: These data indicate that a single 100-mg dose of ABT 639 had no effect on experimental pain induced by intradermal capsaicin injection. PMID- 26814296 TI - Burning Eye Syndrome: Do Neuropathic Pain Mechanisms Underlie Chronic Dry Eye? AB - OBJECTIVE: Dry eye is a multi-factorial disorder that manifests with painful ocular symptoms and visual disturbances, which can only be partly attributed to tear dysfunction. This disorder may also involve neuroplasticity in response to neuronal injury. This review will emphasize the key characteristics of dry eye pain and its pathologic mechanisms, making the argument that a subset of dry eye represents a neuropathic pain disorder of the eye, more appropriately called "burning eye syndrome." METHODS: A literature review was conducted using a PubMed search focusing on dry eye, corneal nociception, and neuropathic pain. Articles were reviewed and those discussing clinical course, pathophysiology, and neuronal regulation of chronic ocular pain as related to dry eye were summarized. RESULTS: We found that there is a discordance between ocular pain and dryness on the ocular surface. Although tear dysfunction may be one of the initial insults, its persistence may be associated with repeated ocular sensory nerve injury leading to an acute-to-chronic pain transition associated with neuropathologic changes (peripheral and central sensitization), neuronal dysfunction, and spontaneous ocular pain. CONCLUSION: Dry eye is becoming a major health concern due to its increasing incidence, significant morbidity, and economic burden. Recent evidence suggests that a subset of dry eye may be better represented as a chronic neuropathic pain disorder due to its features of dysesthesia, spontaneous pain, allodynia, and hyperalgesia. Future therapies targeted at the underlying neuroplasticity may yield improved efficacy for patients with this subset of dry eye, which we term "burning eye syndrome." PMID- 26814295 TI - Reliability and Convergent Validity of the Algometer for Vestibular Pain Assessment in Women with Provoked Vestibulodynia. AB - OBJECTIVE: Women with provoked vestibulodynia (PVD) suffer pain at the entry of the vagina elicited by pressure as during vaginal penetration. To quantify vestibular pain, we developed a new instrument, an algometer. The aim of this study was to investigate the test-retest reliability of the algometer and evaluate its convergent validity for vestibular pain assessment in women with PVD. METHODS: Twenty-six women with PVD participated in the study. Vestibular pain was assessed with the new algometer and the already known vulvalgesiometer during two different sessions 2 to 4 weeks apart. At each session, the pressure pain threshold (PPT) and pressure pain tolerance (PPTol) were measured twice at the 3, 6, and 9 o'clock sites of the vestibule in random order. The test-retest reliability (intra- and inter-session) of the algometer was calculated using the intraclass correlation coefficient (ICC) and standard error of measurement (SEM). Its convergent validity was evaluated by the correlation coefficients between PPTs and PPTols measured by the algometer and those measured with the vulvalgesiometer. RESULTS: Intra-session reliability at all three sites for PPTs and PPTols in both sessions was excellent (ICC = 0.859 to 0.988, P <= 0.002). Inter-session reliability was good to excellent (ICC = 0.683 to 0.922, SEM = 15.06 to 47.04 g, P <= 0.001). Significant correlations were found between the two tools for all sites for PPTs (r = 0.500 to 0.614, P <= 0.009) and PPTols (r = 0.809 to 0.842, P < 0.001). DISCUSSION: Findings showed that the algometer is a reliable and valid instrument for measuring PPTs and PPTols in the vestibular area in women with PVD. This technology is promising for pinpointing treatment mechanisms and efficacy. PMID- 26814297 TI - Migraine, Osmophobia, and Anxiety. AB - OBJECTIVES: To evaluate the association between osmophobia and the characteristics of patients and their headaches, among migraine patients. METHODS: This was a cross-sectional study. Patients who consecutively sought medical attendance in a primary care unit were asked about their headaches over the last 12 months. Those who had migraine were included. A semi-structured interview, the Headache Impact Test and the Hospital Anxiety and Depression Scale were used. RESULTS: 147 patients had migraine; 78 had osmophobia; 60 had significant anxiety symptoms; and 78 had significant depression symptoms. The mean age of these patients was 43.2 years (+/- 13.7); 91.2% were women. The mean length of time with complaints of headache was 13.8 years (+/- 12). Among the migraine patients, those with anxiety, more years of headache history, and phonophobia presented significantly more osmophobia (multivariate logistic regression). CONCLUSION: Osmophobia in migraine patients is associated with significant anxiety symptoms, length of headache history, and phonophobia. PMID- 26814299 TI - Medical Judgments Across the Range of Reported Pain Severity: Clinician and Lay Perspectives. AB - BACKGROUND: While increasing evidence suggests that observers discount high severity chronic pain, factors that occasion such discounting are poorly understood, particularly regarding health provider vs lay perspectives. OBJECTIVE: This study examined the effects of supporting medical evidence and comorbid psychological distress (pain behavior) on medical student and lay clinical judgments of increasingly severe patient pain reports. DESIGN: In a 2 * 2 * 2 * (7) mixed between- and within-subject design, participants (medical students vs lay) made clinical judgments after reading vignettes describing a hypothetical patient that varied in levels of medical evidence and pain behavior (low vs high) and pain severity (4/10-10/10). SUBJECTS: Fourth-year medical students (N = 115) and lay persons in the community (N = 300) participated in this research. RESULTS: While both medical student and lay judgments plateaued at high levels of pain severity, judgments regarding cause (medical vs psychological), treatment (opioid prescription), and disability showed growing divergence as levels of reported pain severity increased. Divergence relative to medical and psychological causes of pain was found irrespective of the level of supporting medical evidence; divergence relative to opioid treatment and support for a disability claim was found when supporting medical evidence was low. CONCLUSIONS: The results indicate differing expectations of chronic pain treatment for health care providers relative to the lay public that could impact clinical care, especially at high pain severity levels, where lay expectations diverge significantly from those of health professionals. PMID- 26814298 TI - An Examination of Pain Catastrophizing and Endogenous Pain Modulatory Processes in Adults with Chronic Low Back Pain. AB - OBJECTIVE: Research on chronic low back pain (cLBP) has focused heavily on structural abnormalities with emphasis on diagnostic imaging. However, for many cLBP patients, clinical pain and disability are not clearly associated with identifiable pathology of the spine or associated tissues. Therefore, alternative determinants such as psychological factors and dysfunctional pain modulatory processes have been suggested to be important. METHODS: This observational study examined differences in pain catastrophizing and endogenous pain modulation between 25 cLBP patients and 25 pain-free controls. Associations among pain catastrophizing, endogenous pain modulatory processes, clinical pain reports, and disability were also examined in cLBP patients. Endogenous pain modulation was examined using temporal summation (TS) of mechanical and heat pain stimuli as well as conditioned pain modulation (CPM) with algometry (test stimulus) and the cold pressor task (conditioning stimulus). RESULTS: Findings demonstrated significantly greater pain catastrophizing as well as greater TS of mechanical and heat pain for cLBP patients compared with controls. CPM was not present in cLBP patients or controls. Among cLBP patients, pain catastrophizing was significantly associated with disability, while TS of mechanical pain was significantly associated with clinical pain severity and disability. CONCLUSIONS: This study suggests that endogenous pain modulatory processes are altered for cLBP patients, particularly TS of mechanical and heat stimuli. Pain catastrophizing and TS of mechanical pain may have important clinical relevance for cLBP, given associations with clinical pain and disability; however, future research is needed to replicate these findings. PMID- 26814300 TI - Methods and Instruments to Evaluate Cognitive Function in Chronic Pain Patients: A Systematic Review. AB - OBJECTIVE: We aimed to systematically review the methods and instruments used to evaluate cognitive function in chronic pain (CP) patients. METHODS: A sensitive search strategy was designed using five databases. Based on the objectives and methodology, we selected cross-sectional studies on adults with chronic non cancer pain in which cognitive function was assessed using validated instruments. The characteristics of the subjects, control groups, and other variables that might affect cognitive function, and the instruments used, were extracted from each article. RESULTS: In the 42 articles identified, 53 instruments were used to assess cognitive function. Chronic pain criteria were defined in 83.3% of the articles and more than half (57.1%) included single diagnosis samples, with fibromyalgia being the most frequent studied (75%). Patients with prior cognitive impairment were excluded in 61.9% of the studies, and a control group was included in 64.3% of the studies. In most cases potential confounding variables were evaluated. More than 14% of the studies used self-report measures, and 73.8% used neuropsychological instruments, particularly for assessing attention (30%) and memory (27.5%). None of the instruments were specifically validated for pain patients and only five studies analyzed the psychometric properties of the instruments. CONCLUSIONS: Various instruments and methods were used to assess cognitive function in CP patients, particularly fibromyalgia patients, but also other cohorts with well-defined CP. The instruments used had been validated, but not for pain populations, thus they require specific adaptation and validation to be used in CP patients. Certain recommendations are made in order to improve the evaluation of cognitive function in these patients. PMID- 26814301 TI - Analysis of Pressure Pain Hypersensitivity, Ultrasound Image, and Quality of Life in Patients with Chronic Plantar Pain: A Preliminary Study. AB - OBJECTIVES: To evaluate widespread pressure pain in patients with chronic plantar heel pain compared with that in healthy controls and to investigate the differences in ultrasound imaging and quality of life between these two groups. METHODS: A total of 22 patients (11 female) with chronic plantar heel pain and the same number of healthy patients, matched according to age and gender, were included in this pilot study. Pressure pain thresholds (PPTs) were bilaterally assessed over the calcaneus bone, the plantar fascia, the first and fifth metatarsals, the soleus muscle, the second metacarpal, and the zygapophyseal joint of C5-C6. Plantar fascia thickness was measured via ultrasound imaging. In addition, quality of life and physical function were assessed using the Short Form 36 (SF-36) questionnaire and the Foot and Ankle Ability Measure (FAAM) questionnaire, respectively. RESULTS: Analysis of covariance (ANCOVA) results showed significant differences in the PPTs at all points between the groups (P < 0.001), but not between sides. The PPTs were significantly lower in the patients than in the controls at all sites (P < 0.05). The results showed significant increases in fascia thickness at the calcaneus insertion (group: F = 74.172, P <= 0.001; side: F = 8.920, P <= 0.001) and the middle fascia point (group: F = 133.685, P = <0.001; side: F = 11.414, P = <0.001) on ultrasound in the patient group compared with the matched control group. The analysis also revealed that the patient group had a significantly lower score on every subscale of the SF-36 and FAAM questionnaires (all P < 0.001), except for the mental component, compared with the matched control group. DISCUSSION: Patients suffering from chronic plantar heel pain showed widespread and bilateral hypersensitivity, increased thickness of the plantar fascia in the affected foot, and deterioration in quality of life and physical functioning compared with matched controls. PMID- 26814302 TI - Pain Medicine Ethics Forum: Key Opinion Leaders with Industry Conflicts of Interest Should Be Able to Hold Leadership Positions in Professional Medical Associations. PMID- 26814303 TI - Professional Medical Associations and Divestiture from Industry: An Ethical Imperative for Pain Society Leadership. PMID- 26814304 TI - Ethics Forum: Conflict of Interest, Part II: Pain Society Leadership and Industry. PMID- 26814305 TI - Assessment of Adults Experiencing Chronic Non-Cancer Pain: A Randomized Trial of Group Versus Individual Format at an Australian Tertiary Pain Service. AB - OBJECTIVE: To compare the outcomes of a new group assessment format with conventional individual assessment. DESIGN: A randomized controlled trial. SETTING: An Australian tertiary hospital multidisciplinary pain service. PATIENTS: Adults referred with chronic non-cancer pain. METHODS: Following attendance at an education and orientation group, 211 participants were randomized to either a group assessment format (focused on supported self assessment) or individual assessment. Follow-up occurred 3 months post-assessment and prior to subsequent pain service intervention. Outcome measures were pain intensity, pain interference, self-efficacy, psychological distress, health care utilization beyond the pain service, waiting time, participant satisfaction, and implementation of self-management strategies. RESULTS: Seventy-two participants undertook group assessment and 90 were assessed individually. Follow-up data were collected on 57 group and 72 individual assessment participants. Results revealed no significant differences between the two assessment formats in outcome with the exception of wait-times. Median wait-time to the first offer of assessment was 47 days for the group format and 144 days for individual. CONCLUSIONS: Group assessment provides a viable alternative to conventional individual assessment. The group assessment reduced wait-times while delivering otherwise comparable outcomes. PMID- 26814306 TI - Pain and Functionality Following Sternotomy: A Prospective 12-Month Observational Study. AB - OBJECTIVE: To document pain levels, functionality, and analgesic use in the 12 months following a sternotomy to identify factors associated with the development of persistent post-sternotomy pain. DESIGN: Prospective observational study. SETTINGS: Royal Hobart Hospital, Australia. SUBJECTS: Patients undergoing a sternotomy between January and November 2013. METHODS: One hundred and ten patients were recruited and followed for 12 months, with telephone calls at 10 days, 6 weeks, 3 months, and 12 months. An initial survey was completed at the point of recruitment including patient history, depression and anxiety scales, self-rated health, and pain catastrophizing scale. RESULTS: The mean age of participants was 69.6 years, with the majority of participants being male (84.5%). The proportion of patients reporting pain in the early post-discharge period was high, with 30% of patients experiencing on average moderate-severe pain in the 10 days following discharge and 11% experiencing on average moderate severe pain at 6 weeks. At 12 months, 15.5% of participants reported on average mild pain and 0.9% an average of moderate-severe pain in the preceding week at their sternotomy site. Pain of neuropathic origin was reported by 41.2% of those with on average daily pain at 12 months. CONCLUSION: This study highlights the need for further research to investigate whether more intensive pain management in the post-discharge period following sternotomy as well as the early identification of patients with neuropathic pain symptoms can reduce the incidence of persistent post-operative pain at 12 months. PMID- 26814307 TI - Impact of Data Imputation Methodology on Pain Assessment over 24 Hours in a Randomized, Placebo-Controlled Study of Gabapentin Enacarbil in Patients with Neuropathic Pain Associated with Postherpetic Neuralgia. AB - OBJECTIVE: To assess the impact of gabapentin enacarbil on primary and secondary pain endpoints using three data imputation methodologies in a randomized phase II study of adult patients with postherpetic neuralgia. METHODS: The primary endpoint was change from baseline to end of maintenance treatment in mean 24-hour average pain intensity score. Secondary endpoints (daytime/nighttime average pain intensity score, daytime/nighttime current pain intensity score, and daytime/nighttime worst pain intensity score) were based on daily electronic diary assessments. Comparisons of each gabapentin enacarbil dose with placebo were performed using three different statistical methodologies: last observation carried forward, baseline observation carried forward, and mixed-effect model for repeated measures. RESULTS: Of the 376 randomized patients, 371 were in the intent-to-treat population (gabapentin enacarbil 1,200 mg, 107; 2,400 mg, 82; 3,600 mg, 87; placebo, 95). For mean 24-hour average pain intensity score, there were statistically significant improvements from baseline to end of maintenance treatment for all gabapentin enacarbil groups vs placebo using the three analysis methods. Significant improvements were also observed for all secondary endpoints with gabapentin enacarbil 1,200 mg using the three analysis methods. Most secondary endpoints also showed improvements following treatment with gabapentin enacarbil 2,400 mg or 3,600 mg compared with placebo. CONCLUSIONS: Gabapentin enacarbil (1,200 mg, 2,400 mg, and 3,600 mg) was effective and well tolerated in patients with postherpetic neuralgia compared with placebo, as confirmed by three different and robust statistical methodologies. PMID- 26814308 TI - Detection of Intravascular Injection During Lumbar Medial Branch Blocks: A Comparison of Aspiration, Live Fluoroscopy, and Digital Subtraction Technology. AB - BACKGROUND CONTEXT: Medial branch blocks may have unrecognized vascular uptake potentially resulting in false- negative results. PURPOSE: To determine the rate of unintended vascular injection of contrast medium during medial branch blocks (MBB) with digital subtraction (DS) technology in the context of negative vascular uptake as determined by live fluoroscopy. STUDY DESIGN/SETTING: Prospective Study in an academic medical center. PATIENT SAMPLE: 344 consecutive MBBs in 80 subjects. OUTCOME MEASURES: The presence of vascular flow as determined by live fluoroscopy and DS technology. METHODS: Unintended vascular injection of contrast medium was determined on 344 consecutive MBBs in 84 subjects, first using live fluoroscopy followed by DS. If live fluoroscopy initially detected vascular uptake, the needle was repositioned until no vascular flow was detected. Once no vascular uptake was confirmed by live fluoroscopy, a contrast medium was then injected while being visualized with DS to again assess the presence or absence of vascular flow undetected by live fluoroscopy. RESULTS: Live fluoroscopy revealed inadvertent vascular uptake in 38 of the 344 blocks [11% (95% CI 8.0-15%)]. DS uncovered an additional 27 of the 344 blocks [7.8% (95% CI 5.3-11.4%)] with evidence of vascular uptake that were not detected with conventional live fluoroscopy. CONCLUSION: DS enhances the ability to detect inadvertent vascular flow during medial branch blocks. This study demonstrates that standard live fluoroscopy can miss a small percentage of cases with unintentional vascular uptake during MBB when compared with DS and may contribute to occasional false-negative responses. PMID- 26814309 TI - Reliability and Accuracy of MRI Laminar Angle Measurements to Determine Intra Procedural Contralateral Oblique View Angle for Cervical or Thoracic Interlaminar Epidural Steroid Injections. AB - BACKGROUND AND OBJECTIVE: Contralateral oblique (CLO) angle view has been a useful addition to standard views in fluoroscopically guided interlaminar epidural injections. Determination of the appropriate CLO angle is paramount in the usefulness of this technique. Using MRI laminar angle measurements as a pre procedural guide for the intra-procedural fluoroscopic CLO angle has been proposed. The purpose of this study was to help determine if using axial MRI laminar measurements prior to a cervical or thoracic epidural steroid injection would be useful in predicting the appropriate fluoroscopic CLO angle. STUDY DESIGN: A retrospective review was performed for patients who underwent cervical or thoracic interlaminar injections. In the performance of interlaminar injections, the authors had routinely determined the true fluoroscopic contra lateral oblique angle after epidural access was confirmed, for use during any potential future injections. The fluoroscopic CLO angle measurements were obtained from a chart review and compared blindly to each patient's MRI axial laminar angle measurements. RESULTS: 34 injections were included. Inter-rater reliability comparing the two authors' MRI angle measurements was considered fair, ICC = 0.395. Accuracy was only 57% comparing MRI laminar angle measurements to within five degrees of the true fluoroscopic CLO angle as determined during the injection procedure. Accuracy by ICC showed only fair agreement, 0.47 and 0.22, for the two authors. CONCLUSIONS: The findings of this study indicate fair inter-rater reliability in manual measurements of laminar angle on axial MRI images. MRI laminar angle measurements do not appear to be highly accurate in determining the appropriate fluoroscopic CLO angle. PMID- 26814310 TI - Unusual Painful Trigeminal Neuropathy Caused by Racemose Neurocysticercosis. PMID- 26814311 TI - Limited Association Between Aerobic Fitness and Pain in Healthy Individuals: A Cross-Sectional Study. AB - OBJECTIVE: In healthy individuals and people with chronic pain, an inverse association between physical activity level and pain has been reported. Associations between objectively measured fitness and pain have also been found in people with chronic pain, but it is not clear whether the same relations are apparent in healthy individuals. The purpose of the present study was to examine the relation between aerobic capacity and pain in healthy individuals. METHODS: Pressure pain threshold, ischemic pain tolerance, and pain ratings during ischemia were assessed and analyzed in relation to aerobic capacity in 35 healthy individuals. Correlation and multiple linear regression were used to analyze the data. Data from previous similar studies in healthy individuals and people with fibromyalgia were extracted and collated by literature review to support interpretation of the experimental data. RESULTS: No relation was found between aerobic capacity and any measure of pain, with the exception of a moderate inverse association between aerobic capacity and lower body pressure pain threshold in males (r = -0.58, P = 0.03) when data from male and female participants were analyzed separately. The limited association between aerobic capacity and quantitative sensory testing of pain was consistent with the data synthesis from previous studies of healthy individuals but differed from studies of people with fibromyalgia. CONCLUSIONS: Aerobic capacity is unrelated to pain in healthy young adults. For people with chronic pain, the negative relation between aerobic capacity and pain presumably arises from the underlying pathophysiology and/or associated behaviors of the disease process. PMID- 26814312 TI - Evolving Pain Services: Preclinic Groups Speed Assessment and Lower Costs. PMID- 26814313 TI - Response: Is It Truly the Answer? Personalized Oxycodone Dosing Based on Pharmacogenetic Testing and Corresponding Pharmacokinetics. PMID- 26814314 TI - Five-year Effects of Chlorhexidine on the In Vitro Durability of Resin/Dentin Interfaces. AB - PURPOSE: To evaluate the effect of an acid containing 2% chlorhexidine (Ac/CHX) or a 2% CHX aqueous solution (Aq/CHX) on the immediate and 5-year bonding properties of resin/dentin interfaces produced by two adhesives. The presence of CHX in these interfaces was also evaluated under micro-Raman spectroscopy. MATERIALS AND METHODS: Forty-two molars were ground to expose a flat dentin surface. In the control group, the surfaces were etched with conventional phosphoric acid, and Prime&Bond NT (PB) and Adper Single Bond 2 (SB) were applied. In Ac/CHX, an acid containing 2% CHX was applied after adhesive application. In the Aq/CHX group, an aqueous solution of 2% CHX was applied for 60 s after etching. After placing the restoration, specimens were prepared and tested using the microtensile bond strength test (MUTBS, 0.5 mm/min) immediately or after 5 years. For nanoleakage (NL), specimens at each period were immersed in silver nitrate solution and examined by EDX-SEM. In addition, specimens at each period underwent examination for CHX using micro-Raman spectroscopy. Data were submitted to appropriate statistical analysis (a=0.05). RESULTS: After 5 years, NL was more pronounced in the control than in the Ac/CHX or Aq/CHX (p<0.001). Significant reductions in the MUTBS were observed for all groups; however, they were more pronounced for the control (p<0.001). CHX was still present in the hybrid layers Ac/CHX or Aq/CHX groups after 5 years. CONCLUSION: The use of a 2% chlorhexidine-containing acid or the application of an aqueous CHX primer may increase the long-term stability of resin/dentin interfaces. PMID- 26814315 TI - Influence of the Oxygen-inhibited Layer on Bonding Performance of Dental Adhesive Systems: Surface Free Energy Perspectives. AB - PURPOSE: To examine the influence of the oxygen inhibited layer (OIL) on shear bond strength (SBS) to dentin and surface free energy (SFE) characteristics of different adhesive systems. MATERIALS AND METHODS: Three adhesive systems were used: Scotchbond Multipurpose (SM), Clearfil SE Bond (CS), and Scotchbond Universal (SU). Resin composite was bonded to dentin surfaces to determine SBS with and without OIL of adhesives. The SFE, dispersion force (gammaSd), polarity force (gammaSp), and hydrogen bonding force (gammaSh) of cured adhesives with and without an OIL were measured. Two-way ANOVA and Tukey's honestly significant difference (HSD) test were used for analysis of SBS data, and one-way ANOVA and Tukey's HSD test were used for the SFE and contact angle data. RESULTS: The SBS of SM and CS showed no significant differences between specimens with and without the OIL. However, the SBS of SU with the OIL was significantly higher than without the OIL. The SFE, gammaSp, and gammaSh of cured adhesives with an OIL were significantly higher than those of cured adhesives without an OIL. The SFE, gammaSp, and gammaSh of SM and CS with an OIL were significantly higher than those of SU with an OIL. CONCLUSION: The results of this study indicate that the presence of an OIL with a single-step self-etching adhesive promotes higher SBS to dentin, unlike in the other types of adhesive systems. The SFE characteristics of the OIL of dental adhesives differed depending on the type of adhesive system. PMID- 26814316 TI - Effects of Dentin Moisture on Cementation of Fiber Posts to Root Canals. AB - PURPOSE: Achieving optimal moisture inside the root canal is a challenge during bonding of fiberglass posts. This study evaluated the effect of different moisture patterns on the push-out bond strength (PBS) and nanoleakage (NL) of fiber posts bonded to the root canal of two simplified etch-and-rinse adhesives. MATERIALS AND METHODS: The roots of 72 human premolars were endodontically prepared and divided into 6 groups according to the combination of the main factors: adhesive (Ambar and Adper Single Bond 2) and moisture (dry, wet, and overwet). The posts were cemented and after 1 week, the roots were cross sectioned into 6 disks. Two disks each were obtained from the cervical, middle, and apical thirds, and the PBS test was carried out (0.5 mm/min; n = 8). The NL was evaluated by scanning electron microscopy after the immersion of specimens in 50% silver nitrate (n = 4). The failure pattern was examined on all debonded specimens. Data were analyzed by three-way repeated measures ANOVA and Tukey's test (5%). RESULTS: For both adhesives, higher PBS values and lower NL were observed in the wet groups, and lower PBS and higher NL in the dry group. In general, the overwet condition showed intermediate results. CONCLUSIONS: The root dentin walls should be left slightly moist before performing fiber post cementation procedures. PMID- 26814317 TI - Durability of Resin-Zirconia Bonds Produced Using Methods Available in Dental Practice. AB - PURPOSE: To evaluate the strength, after artificial aging, of resin-zirconia bonds yielded by methods available in dental practice. MATERIALS AND METHODS: Standardized test specimens consisting of composite resin cylinders cemented to Y TZP disks were assigned to 24 groups (n=20 per group) on the basis of the surface conditioning of the disks and the adhesive used (cement+manufacturer-specific primer). Conditioning methods were: none (control), airborne particle abrasion (50-MUm Al2O3 at 0.05, 0.10, or 0.25 MPa), or tribochemical silica coating (Rocatec or CoJet). Panavia 21+Clearfil Ceramic Primer, Multilink Automix+Monobond Plus, BiFix QM+Ceramic bond, or RelyX Ultimate+Scotchbond Universal were used for cementation. Specimens were stored in water at 37 degrees C either for 3 days or for 150 days in conjunction with 37,500 thermocycles before being submitted to a tensile test (crosshead speed: 1 mm/min). Nonparametric ANOVA and post-hoc tests within the same model were applied to the results (alpha=0.05). RESULTS: Conditioning, cement, aging, and all their interactions significantly affected bond strength (p<0.0001). After storage in water for 3 days, bond strengths ranged between 4 and 45 MPa (values were lowest in the BiFix QM groups). After long-term aging, the best results were obtained for silica-coated (Rocatec) zirconia samples cemented with Panavia 21/Clearfil Ceramic Primer; this was the only group for which bond strengths were >10 MPa. Premature failure of the resin-ceramic bond was usually observed during long-term aging, the only exception being the non-control groups cemented with Panavia. CONCLUSION: Most bonding strategies failed to create bonds to zirconia with acceptable strength after long-term aging. It might therefore be unwise to rely solely on adhesion for retention of load-bearing Y-TZP restorations. PMID- 26814318 TI - Adhesive Systems as an Alternative Material for Color Masking of White Spot Lesions: Do They Work? AB - PURPOSE: To evaluate the color masking effect of infiltration treatment of artificial white spot lesions (AWSL) using a dedicated resin in comparison to different adhesive systems. MATERIALS AND METHODS: Enamel/dentin specimens were obtained from bovine incisors and baseline color was assessed using a reflectance spectrophotometer, according to the CIE L*a*b* system. AWSL were produced using a buffered acid solution and a new color evaluation was performed. The specimens were divided into 8 groups: control: artificial saliva changed daily for 7 days; IC: infiltrating resin Icon; EC: EquiaCoat; FU: Futurabond U; SBU: Single Bond U; SBMP: Scotchbond MP; OB: OptibondFL; BF: Bioforty. After the treatments, the color was evaluated again and the values for the parameters DeltaL (change in lightness), Deltaa (change in chroma), Deltab (change in hue), and DeltaE (general color difference) were calculated in relation to baseline. Data were analyzed by one-way ANOVA and Tukey's tests. RESULTS: After treatment, ANOVA showed significant differences for all parameters (p = 0.001). Tukey's test showed the greatest lightness reduction (DeltaL) for the IC group, followed by EC, FU, and SBU. The SBMP, OB, and BF groups were similar to the control. For Deltab values, all groups showed differences in relation to the control, with no differences between them. In relation to DeltaE, all groups showed differences in relation to the control (DeltaE = 5.24), with no significant differences between them. DeltaE values after application of all resinous materials were lower than the threshold of 3.7, indicating effective color masking. CONCLUSIONS: The Icon infiltrant produced a greater lightness reduction of white lesions (DeltaL). For general color difference (DeltaE), all the resinous materials tested were able to color mask artificial AWSL. PMID- 26814319 TI - Clinical Evaluation of Indirect Composite Resin Restorations Cemented with Different Resin Cements. AB - PURPOSE: To clinically evaluate the performance of indirect composite resin restorations cemented with conventional and self-adhesive resin cements over a 12 month period. MATERIALS AND METHODS: Ten patients fulfilled all the inclusion criteria. Twenty-four composite resin restorations were performed using an indirect technique and cemented with a resin cement (RelyX ARC) or a self adhesive resin cement (RelyX U100). Two independent evaluators analyzed the restorations using modified USPHS criteria after periods of two weeks and 6 and 12 months. Statistical significance between the cements at each timepoint was evaluated with the Wilcoxon test and between timepoints with the Mann-Whitney test, both at a significance level of 5%. Fisher's exact test was used to assess the occurrence of absolute failures. RESULTS: No statistically significant differences were found between the groups at the same timepoint nor between groups at different timepoints. The only significant difference was found for color match for both groups after 12 months. CONCLUSION: After 12 months, indirect composite resin restorations cemented with self-adhesive resin cement performed similarly to those cemented with conventional resin cement. PMID- 26814320 TI - Influence of Cavity Margin Design and Restorative Material on Marginal Quality and Seal of Extended Class II Resin Composite Restorations In Vitro. AB - PURPOSE: To investigate the influence of three cavity designs on the marginal seal of large Class II cavities restored with low-shrinkage resin composite limited to the enamel. MATERIALS AND METHODS: One hundred twenty (120) intact human molars were randomly divided into 12 groups, with three different cavity designs: 1. undermined enamel, 2. box-shaped, and 3. proximal bevel. The teeth were restored with 1. an extra-low shrinkage (ELS) composite free of diluent monomers, 2. microhybrid composite (Herculite XRV), 3. nanohybrid composite (Filtek Supreme XTE), and 4. silorane-based composite (Filtek Silorane). After artificial aging by thermocycling and storage in physiological saline, epoxy resin replicas were prepared. To determine the integrity of the restorations' approximal margins, two methods were sequentially employed: 1. replicas were made of the 120 specimens and examined using SEM, and 2. the same 120 specimens were immersed in AgNO3 solution, and the dye penetration depth was observed with a light microscope. Statistical analysis was performed using the Kruskal-Wallis and the Dunn-Bonferroni tests. RESULTS: After bevel preparation, SEM observations showed that restorations did not exhibit a higher percentage of continuous margin (SEM-analysis; p>0.05), but more leakage was found than with the other cavity designs (p<0.05). The lowest percentage of continuous margin was observed in ELS restorations (p<0.05). More fractured margins were observed in the undermined enamel cavity design groups (p<0.05). CONCLUSION: Bevel preparation failed to improve margin quality in large Class II composite restorations and is no longer recommended. However, undermined enamel should be removed to prevent enamel fractures. PMID- 26814324 TI - [Injuries to the upper limbs - the anatomist cooperation with the clinician]. PMID- 26814321 TI - [Data for surgery]. PMID- 26814325 TI - [Not Available]. PMID- 26814327 TI - [Pathology of transplantations II]. PMID- 26814326 TI - [Not Available]. PMID- 26814328 TI - [Not Available]. PMID- 26814329 TI - Introduction. PMID- 26814330 TI - Retraction Note: Adenosine triphosphate treatment for supraventricular tachycardia in infants. AB - Retraction Note to: Eur J Pediatr (1994) 153:668-671 DOI 10.1007/BF02190689. This article, "Adenosine triphosphate treatment for supraventricular tachycardia in infants", published in the European Journal of Pediatrics (1994) 153/9: 668-671, Springer-Verlag 1994, has been retracted at the request of the Publisher as it is a duplicate of the paper "Adenosine-tri-phosphate treatment for supraventricular tachycardia in infants", that has been published with further corrections in Vol. 153/11: 793-796, of the same journal. PMID- 26814331 TI - Adjuvant vs.salvage radiotherapy for patients at high risk for recurrence after radical prostatectomy. AB - Prostate cancer patients with adverse pathologic factors (i.e., positive surgical margin, pT3 disease) after radical prostatectomy are more likely not cured (>60%) than cured by surgery alone. Adjuvant radiotherapy compared with observation reduces recurrence by 49% to 57%, may improve overall survival, and improves long term quality of life without increased long-term patient-reported urinary or gastrointestinal tract symptoms. Despite these results, adjuvant radiotherapy is uncommonly received by patients with these adverse factors.We discuss the rationale for adjuvant therapy as part of oncologic treatment and potential reasons why patients do not receive adjuvant radiotherapy in prostate cancer. We conclude that patients need a thorough discussion regarding the potential benefits and harms of both approaches (watch and wait vs. adjuvant radiotherapy) to make an informed decision. PMID- 26814332 TI - The Coronary Sinus Reducer improves angina and ischaemia by redistribution of blood from non-ischaemic to ischaemic myocardium. PMID- 26814333 TI - Perioperative management of nail polish, artificial nails and piercings in The Netherlands: A survey study. PMID- 26814334 TI - A facile and cheap synthesis of zwitterion coatings of the CS@PGMA@IDA nanomaterial for highly specific enrichment of glycopeptides. AB - CS@PGMA@IDA nanomaterials were facilely synthesized, the zwitterion polymer surface PGMA@IDA endows the nanomaterial with biocompatibility, excellent hydrophilic properties and a large amount of functional groups on the polymer chains that can selectively bind to glycopeptides based on hydrophilic interaction. PMID- 26814336 TI - Management of a giant perineal condylomata acuminata. AB - A condylomata acuminata infection is caused by human papillomaviridae (HPV). This sexually transmitted condition most often affects the perineal region. Importantly, infections with types 16 and 18 are associated with an increased risk for anal and cervix cancer. In most cases topical therapy is sufficient for successfully treating condylomata acuminata. Here, we report the case of a 51 year old patient who suffered from a giant perianal located condylomata acuminata which had developed over a period of more than 10 years. Imaging by MRI revealed a possible infiltration of the musculus sphincter ani externus. Because a topical treatment or a radiotherapy was considered unfeasible, a surgical treatment was the only therapeutic option in this unusual case. First, a colostomy was performed and subsequently a resection of the tumor in toto with circular resection of the external portion of the musculus sphincter ani externus was performed. The large skin defect was closed by two gluteus flaps. The rectum wall was reinserted in the remnant of the musculus sphincter ani externus. Postoperatively, parts of the flaps developed necrosis. Therefore, a vacuum sealing therapy was initiated. Subsequently, the remaining skin defects were closed by autologous skin transplantation. Six months later the colostomy could be reversed. To date, one year after first surgery, the patient has still a normal sphincter function and no recurrence of the condylomata acuminata. This case report demonstrates how giant condylomata acuminata can be successfully treated by extended surgical procedures including colostomy and plastic reconstruction of resulting defects upon resection. PMID- 26814338 TI - Exploring the role of synaptic layering. PMID- 26814339 TI - Putting the brakes on CRISPR-Cas9 gene drive systems. PMID- 26814335 TI - F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signalling. AB - During immune surveillance and inflammation, leukocytes exit the vasculature through transient openings in the endothelium without causing plasma leakage. However, the exact mechanisms behind this intriguing phenomenon are still unknown. Here we report that maintenance of endothelial barrier integrity during leukocyte diapedesis requires local endothelial RhoA cycling. Endothelial RhoA depletion in vitro or Rho inhibition in vivo provokes neutrophil-induced vascular leakage that manifests during the physical movement of neutrophils through the endothelial layer. Local RhoA activation initiates the formation of contractile F actin structures that surround emigrating neutrophils. These structures that surround neutrophil-induced endothelial pores prevent plasma leakage through actomyosin-based pore confinement. Mechanistically, we found that the initiation of RhoA activity involves ICAM-1 and the Rho GEFs Ect2 and LARG. In addition, regulation of actomyosin-based endothelial pore confinement involves ROCK2b, but not ROCK1. Thus, endothelial cells assemble RhoA-controlled contractile F-actin structures around endothelial pores that prevent vascular leakage during leukocyte extravasation. PMID- 26814341 TI - Repair and rescue for muscular dystrophy. PMID- 26814342 TI - A new model of Huntington's disease. PMID- 26814344 TI - Advancing science by leaps and bounds. PMID- 26814345 TI - Use of FOIA by animal rights activists. PMID- 26814346 TI - Refinement, a part of a three-legged stool. PMID- 26814347 TI - Should refinement 'mess with success'? PMID- 26814348 TI - A mutual understanding can promote progress. PMID- 26814349 TI - A necessary consideration. PMID- 26814350 TI - A word from USDA and OLAW. PMID- 26814351 TI - Altered states part 2: addressing nausea in canine research subjects. AB - Nausea and emesis can occur for multiple reasons. While research staff can readily empathize with this type of discomfort, proper assessment and treatment can be challenging. In order to provide optimal care for canine research subjects, it is critical that institutions develop a treatment plan and take preemptive measures to control nausea and emesis when they occur. PMID- 26814352 TI - Antibody production in rabbits administered Freund's complete adjuvant and carprofen concurrently. AB - Freund's complete adjuvant (FCA) is a commonly used immunopotentiator that can boost polyclonal antibody production in animal models such as rabbits, but FCA is also known to cause inflammation and pain. It is important to balance the welfare of animals with the goal of efficiently producing antibodies, but little is known about how common treatments for pain and inflammation, such as non-steroidal anti inflammatory drugs (NSAIDs), affect the production of polyclonal antibodies. The purpose of this study was to measure polyclonal antibody production in rabbits that were administered FCA either with or without a concurrent treatment of a NSAID, carprofen. Rabbits were divided into two groups and were administered identical treatments of an antigen with adjuvant, and the treatment group also received carprofen injections at different stages of the study. Carprofen treatment did not significantly affect polyclonal antibody production, which suggests that carprofen and other NSAIDs can be used alongside FCA in rabbits to achieve desired levels of antibody production while minimizing pain and distress associated with the use of FCA. PMID- 26814354 TI - Education is becoming! PMID- 26814353 TI - Common swine models of cardiovascular disease for research and training. AB - Cardiovascular diseases are a major health concern and therefore an important topic in biomedical research. Large animal models allow researchers to assess the safety and efficacy of new cardiovascular procedures in systems that resemble human anatomy; additionally, they can be used to emulate scenarios for training purposes. Among the many biomedical models that are described in published literature, it is important that researchers understand and select those that are best suited to achieve the aims of their research, that facilitate the humane care and management of their research animals and that best promote the high ethical standards required of animal research. In this resource the authors describe some common swine models that can be easily incorporated into regular practices of research and training at biomedical institutions. These models use both native and altered vascular anatomy of swine to carry out research protocols, such as testing biological reactions to implanted materials, surgically creating aneurysms using autologous tissue and inducing myocardial infarction through closed-chest procedures. Such models can also be used for training, where native and altered vascular anatomy allow medical professionals to learn and practice challenging techniques in anatomy that closely simulates human systems. PMID- 26814355 TI - It takes a village, not a federal law. PMID- 26814356 TI - Training and caring for primates. AB - Ms. Andrews-Kelly recounts the experiences and inspirations that have guided her career in providing care, enrichment and training for non-human primates. PMID- 26814357 TI - Oxidative Stress in Obese Postmenopausal Women: An Additive Burden for Atherosclerosis. AB - INTRODUCTION: Coronary Artery Disease are on the rise in the general population and is the leading cause of death in both men and women. The impact of CAD is underappreciated in younger women when compared to men. Women have unique risk factors for CAD and postmenopausal women are at higher risk of developing CAD when compared to normal menstruating women. AIM: The aim of our study was to find out the difference in oxidative stress levels between obese postmenopausal women and normal menstruating women, also to compare the same in normal weight postmenopausal women. MATERIALS AND METHODS: Thirty one normal and 29 obese postmenopausal women with age more than 45 years who visited obstetrics and gynaecology outpatient department for general clinical evaluation at a tertiary care centre were recruited in this cross-sectional study. Thirty normal menstruating women were compared. Anthropometric measurements were recorded and the body mass index was calculated. Serum Malondialdehyde and superoxide dismutase was measured using a spectrophotometer. RESULTS: There was a significant difference in mean MDA levels in postmenopausal women (1.477 +/- 0.359) when compared to normal menstruating women (0.666 +/- 0.302) (p < 0.01). There was no significant difference in mean SOD levels in postmenopausal women (2.836 +/- 0.899) when compared to normal menstruating women (2.986 +/- 0.686) (p > 0.05). Also, there was a significant increase between mean MDA levels in obese postmenopausal women (2.48 +/- 0.52) when compared to normal weight postmenopausal women (1.65 +/- 0.36) (p < 0.01). There was a significant difference between mean SOD levels in obese postmenopausal women (1.36 +/- 0.96) and normal weight postmenopausal women (2.56 +/- 1.03) (p < 0.01). CONCLUSION: The oxidative stress was higher in obese postmenopausal women when compared to normal weight postmenopausal women and normal menstruating women. PMID- 26814358 TI - A New, Simple and Versatile Strategy for the Synthesis of Short Segments of Zigzag-Type Carbon Nanotubes. AB - Short segments of zigzag single-walled carbon nanotubes (SWCNTs) were obtained from a calixarene scaffold by using a completely new, simple and expedited strategy that allowed fine-tuning of their diameters. This new approach also allows for functionalised short segments of zigzag SWCNTs to be obtained; a prerequisite towards their lengthening. These new SWCNT short segments/calixarene composites show interesting behaviour in solution. DFT analysis of these new compounds also suggests interesting photophysical behaviour. Along with the synthesis of various SWCNTs segments, this approach also constitutes a powerful tool for the construction of new, radially oriented pi systems. PMID- 26814359 TI - An Uncommon Cause for Polyuria. PMID- 26814360 TI - Microcantilever Actuation by Laser Induced Photoacoustic Waves. AB - We present here a combined theoretical and experimental investigation on effective excitation of microcantilever by using photoacoustic waves. The photoacoustic waves arose from a vibrating Al foil induced by an intensity modulated laser. We demonstrate that, superior to photothermal excitation, this new configuration avoids direct heating of the microcantilever, thus minimizing undesired thermal effects on the vibration of microcantilever, while still keeps the advantage of being a remote, non-contact excitation method. We also measured the vibration amplitude of the microcantilever as a function of distance between the microcantilever and the Al foil and found that the amplitudes decay gradually according to the inverse distance law. This method is universal and can be adopted in bio-microelectromechanical systems (BioMEMs) for the detection of small signals where detrimental thermal effects must be avoided. PMID- 26814361 TI - CTRP9 Ameliorates Pulmonary Arterial Hypertension Through Attenuating Inflammation and Improving Endothelial Cell Survival and Function. AB - Endothelial dysfunction and inflammation are believed to be 2 primary instigators of pulmonary arterial hypertension (PH). C1q/TNF-related protein 9 (CTRP9) plays important roles in anti-inflammation and improvement of epithelial function. However, the role of CTRP9 in the progression of PH remains still unclear. In this study, the role and mechanism of CTRP9 in the PH progression were explored. First, serum CTRP9 contents and CTRP9 mRNA expression in the pulmonary artery epithelial cells from patients with PH were detected. Our data on enzyme-linked immunosorbent assay and real-time quantitative Polymerase Chain Reaction showed that CTRP9 mRNA and protein content were markedly downregulated in the patients with PH. Then the pcDNA-CTRP9 expression vector or CTRP9 siRNA was transfected into the primary pulmonary artery epithelial cells from the patients with PH in vitro. CTRP9 overexpression significantly improved endothelial NOS protein expression and reduced the secretion of endothelin-1 (ET-1) and matrix metalloproteinase-2 (MMP-2), whereas knockdown of CTRP9 sharply reduced eNOS protein expression and promoted the secretion of ET-1 and MMP-2 in the cultured human epithelial cells. Moreover, the levels of phosphatidylinositol 3-kinase (PI3K) and pAkt were reduced in the epithelial cells and CTRP9 overexpression activated the PI3K/Akt pathway. CTRP9 could inhibit cell apoptosis and eNOS expression reduction in the cells pretreated with the PI3K/Akt inhibitor LY294002 and resist LY294002-induced ET-1 and MMP-2 secretion. Finally, to verify the role of CTRP9 in the progression of PH in vivo, the pcDNA-CTRP9 expression vector or CTRP9 siRNA was intravenously injected into rats with PH. Pulmonary arterial pressures of the rats were notably reduced by the pcDNA-CTRP9 injection and elevated by the CTRP9 siRNA injection. In conclusion, CTRP9 ameliorated PH by attenuating inflammation and improving endothelial cell survival and function. PMID- 26814362 TI - First report on the nationwide incidence and prevalence of Type 1 diabetes among children in Turkey. AB - AIM: To report, for the first time, the incidence and prevalence of childhood Type 1 diabetes in Turkey using a nationwide registry. METHODS: Information on birth date, city of birth, diagnosis date and gender of all patients with Type 1 diabetes aged < 18 years were obtained from the Turkish Social Security Institute for the period from January 2011 to December 2013. RESULTS: There were 17 175 prevalent cases of Type 1 diabetes over the 3-year period. The prevalence of Type 1 diabetes was 0.75/1 000 (95% CI 0.74-0.76) and was higher in girls than in boys (0.79 vs 0.72 /1 000; P < 0.01). There were 2465 incident cases in 2013. The incidence was slightly higher among girls (50.6%) than boys (49.4%); the girl:boy case ratio was 1.02. The incidence was 10.4/100 000 for boys and 11.3/100 000 for girls. The age-standardized incidence rate was 10.8 per 100 000 (95% CI 10.1 11.5) according to the WHO standard population, estimated using the direct method. The mean patient age at diagnosis was 10.6 +/- 4.6 years. The highest proportion of cases (40.6%) was diagnosed in children aged 10-14 years. CONCLUSIONS: This is the first study to report the incidence and prevalence of Type 1 diabetes in children in Turkey. The incidence of Type 1 diabetes reflects the geographical location of Turkey, bridging Asia and Europe, with the incidence being higher than in Asia but lower than in Europe. PMID- 26814363 TI - HLA-A, -B, -C, -DR, and -DQ Matching in Pancreas Transplantation: Effect on Graft Rejection and Survival. AB - To enhance selection of appropriate deceased donors for pancreas transplants, we sought to determine whether HLA matching improved posttransplantation outcomes. In this single-center study of 1219 pancreas transplants, we correlated posttransplantation outcomes with HLA-A, -B, -C, -DR, and -DQ matches and mismatches. Rejection was linearly correlated with the number of mismatches. The individual number of HLA mismatches reached significance at four or more with a 2.3- to 2.9-fold increase in rejection. The effect was most predominant with HLA B (1.8-fold with one mismatch and 2.0-fold with two mismatches) and -DR (1.9-fold with two mismatches) loci, whereas HLA-A, -C, and -DQ matches or mismatches did not independently predict acute rejection. The affect was strongest in solitary pancreas transplants, with little impact for simultaneous pancreas and kidney (SPK). In contrast, HLA matching did not affect graft or patient survival rates but was associated with a reduced risk of opportunistic infection. Avoidance of acute rejection saved an estimated $32 000 for solitary pancreas recipients and $52 000 for SPK recipients in hospital costs. Our data do not support the use of HLA matching for predicting pancreas graft survival but do support its significance for the reduction of acute rejection, particularly for solitary pancreas recipients. PMID- 26814364 TI - Reductive amination-assisted quantitation of tamoxifen and its metabolites by liquid phase chromatography tandem mass spectrometry. AB - Tamoxifen, a hormonal therapy drug against estrogen receptor-positive breast cancer, can be metabolized by cytochrome P450 enzymes such as CYP3A4 and CYP3A5, and converted to N-desmethyltamoxifen, which is subsequently, metabolized by CYP2D6 and inverted to form 4-hydroxy-N-desmethyltamoxifen (endoxifen). Conventional mass spectrometry (MS) analyses of tamoxifen and its metabolites require isotopic internal standards (ISs). In this study, endoxifen and N desmethyltamoxifen amine groups were modified by reductive amination with formaldehyde-D2 to produce new metabolite molecules. Both endoxifen and N desmethyltamoxifen generated their corresponding D2-methyl modified analogs. This method is expected to simplify MS detection and overcome the difficulty in selecting adequate ISs when tamoxifen metabolites are analyzed by absolute quantification. It identified tamoxifen, D2-methyl modified endoxifen, and D2 methyl modified N-desmethyltamoxifen with a linearity ranging from 2 to 5000 ng/mL with correlation coefficient (R(2)) values of 0.9868, 0.9849, and 0.9880, respectively. Furthermore, this reductive amination-based method may enhance the signal intensities of D2-methyl modified N-desmethyltamoxifen and endoxifen, thus facilitating the MS detection. PMID- 26814365 TI - Fractionation of dextrin by gradient polyethylene glycol precipitation. AB - This work aimed at developing a novel approach, named gradient polyethylene glycol (PEG) precipitation, to fractionate dextrin into fractions with narrower molecular weight distribution. This approach was based on the incompatibility between PEG and dextrin in aqueous solution; this incompatibility is positively correlated with the molecular weight of dextrin. Theoretically, dextrin can be precipitated in descending order of molecular weight by the gradual addition of PEG into the dextrin solution. Specifically, this study investigated the effects of molecular weight and its distribution of PEG on dextrin fractionation with the molecular-weight dispersity (DM) as index. The parent dextrin could be fractionated by PEG into several fractions with different molecular weights and lower DM. The average DM of fractions obtained by PEG2000, PEG4000, PEG6000, PEG10000, and PEG20000 was 1.471, 1.352, 1.286, 1.453, and 2.028, respectively, while the DM of the parent dextrin was 2.052. These data suggest that PEG6000 was the optimal precipitant, while PEG20000 was unsuitable for fractionating dextrin. Furthermore, narrowly-distributed PEG resulted in optimum fractionation results. Therefore, gradient PEG precipitation is an efficient method for fractionating dextrin. Additionally, narrowly-distributed PEG of suitable molecular weight should be selected to obtain superior fractionation results. PMID- 26814366 TI - Magnetic hydrophilic-lipophilic balance sorbent for efficient extraction of chemical warfare agents from water samples. AB - Magnetic hydrophilic-lipophilic balance (MHLB) hybrid resin was prepared by precipitation polymerization using N-vinylpyrrolidone (PVP) and divinylbenzene (DVB) as monomers and Fe2O3 nanoparticles as magnetic material. These resins were successfully applied for the extraction of chemical warfare agents (CWAs) and their markers from water samples through magnetic dispersive solid-phase extraction (MDSPE). By varying the ratios of monomers, resin with desired hydrophilic-lipophilic balance was prepared for the extraction of CWAs and related esters of varying polarities. Amongst different composites Fe2O3 nanoparticles coated with 10% PVP+90% DVB exhibited the best recoveries varying between 70.32 and 97.67%. Parameters affecting the extraction efficiencies, such as extraction time, desorption time, nature and volume of desorption solvent, amount of extraction sorbent and the effect of salts on extraction were investigated. Under the optimized conditions, linearity was obtained in the range of 0.5-500 ng mL(-1) with correlation ranging from 0.9911-0.9980. Limits of detection and limits of quantification were 0.5-1.0 and 3.0-5.0 ng mL(-1) respectively with RSDs varying from 4.88-11.32% for markers of CWAs. Finally, the developed MDSPE method was employed for extraction of analytes from water samples of various sources and the OPCW proficiency test samples. PMID- 26814368 TI - Gyre-driven decay of the Earth's magnetic dipole. AB - Direct observations indicate that the magnitude of the Earth's magnetic axial dipole has decreased over the past 175 years; it is now 9% weaker than it was in 1840. Here we show how the rate of dipole decay may be controlled by a planetary scale gyre in the liquid metal outer core. The gyre's meridional limbs on average transport normal polarity magnetic flux equatorward and reverse polarity flux poleward. Asymmetry in the geomagnetic field, due to the South Atlantic Anomaly, is essential to the proposed mechanism. We find that meridional flux advection accounts for the majority of the dipole decay since 1840, especially during times of rapid decline, with magnetic diffusion making an almost steady contribution generally of smaller magnitude. Based on the morphology of the present field, and the persistent nature of the gyre, the current episode of dipole decay looks set to continue, at least for the next few decades. PMID- 26814367 TI - Pathogenicity of the Korean H5N8 highly pathogenic avian influenza virus in commercial domestic poultry species. AB - In 2014, the highly pathogenic avian influenza (HPAI) virus H5N8 triggered outbreaks in wild birds and poultry farms in South Korea. In the present study, we investigated the pathogenicity of the H5N8 HPAI virus, belonging to the clade 2.3.4.4, in different species of poultry. For this, we examined clinical signs and viral shedding levels following intranasal inoculation of the virus in 3-week old commercial layer chickens and quails, 10-week-old Korean native chickens, and 8-week-old Muscovy ducks. Intranasal inoculation with 10(6.0) viruses at 50% egg infective dose resulted in 100% mortality in the layer chickens (8/8) and quails (4/4), but 60% and 0% deaths in the Korean native chickens (3/5) and Muscovy ducks (0/4), respectively. In addition, transmission of the inoculated virus to contact-exposed birds was evident in all the species used in this study. Based on our results, we conclude that the H5N8 HPAI virus has lower pathogenicity and transmissibility in poultry species compared with previously reported H5N1 HPAI viruses. PMID- 26814369 TI - Private capital investments in health care provision through mergers and acquisitions: from long-term to acute care. AB - OBJECTIVES: This work aims to test whether different segments of healthcare provision differentially attract private capital and thus offer heterogeneous opportunities for private investors' diversification strategies. METHODS: Thomson Reuter's SDC Platinum database provided data on 2563 merger and acquisition (M&A) deals targeting healthcare providers in Western Europe between 1990 and 2010. Longitudinal trends of industrial and geographical characteristics of M&As' targets and acquirers are examined. RESULTS: Our analyses highlight: (i) a relative decrease of long-term care facilities as targets of M&As, replaced by an increasing prominence of general hospitals, (ii) a shrinking share of long-term care facilities as targets of financial service organizations' acquisitions, in favor of general hospitals, and (iii) an absolute and relative decrease of long term care facilities' role as target of cross-border M&As. CONCLUSIONS: We explain the decreasing interest of private investors towards long-term care facilities along three lines of reasoning, which take into account the saturation of the long-term care market and the liberalization of acute care provision across Western European countries, regulatory interventions aimed at reducing private ownership to ensure resident outcomes and new cultural developments in favor of small-sized facilities, which strengthen the fragmentation of the sector. These findings advance the literature investigating the effect of private ownership on health outcomes in long-term facilities. Market, policy and cultural forces have emerged over two decades to jointly regulate the presence of privately owned, large-sized long-term care providers, seemingly contributing to safeguard residents' well-being. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26814370 TI - Profiles of delirium and the clinical outcomes of patients who underwent coronary artery bypass grafting: a prospective study from China. AB - AIMS AND OBJECTIVES: To explore the profiles of delirium in coronary artery bypass grafting patients and identify related patient outcomes. BACKGROUND: Delirium was assessed previously as a binary result, i.e. present or absent, but little attention was paid to the profiles of delirium, e.g. the subtype, severity, duration and the first episode, and little was known about clinical outcomes. DESIGN: A prospective study. METHODS: Ninety-five delirious patients who underwent coronary artery bypass grafting were included. Delirium episodes were categorised as hypoactive, hyperactive or mixed type and as mild, moderate or severe. Duration in days and the first episode of delirium in day after surgery were recorded. Patient outcomes were recorded prospectively to determine the effects of delirium profiles. RESULTS: Mixed-type delirium was most common (44.21%), followed by hyperactive delirium (26.32%) and hypoactive delirium (29.47%). Patients with hypoactive delirium had a longer duration of ventilator use. Severity of delirium measurements revealed 28.42% mild, 51.58% moderate and 20.00% severe. Patients with severe delirium had a longer duration of ventilation use, longer lengths of intensive care unit stay and hospital stay compared to mild and moderate delirium. Delirium duration lasted from 1-5 days. Differences were observed in the length of intensive care unit stay and hospital days across groups of different delirium duration. A total of 73.68% of delirium developed on the first and second postoperative days. The later the first episode of delirium occurred, the longer the duration of delirium was, which also yielded longer lengths of intensive care unit stay. CONCLUSION: Hypoactive delirium, severe delirium and delirium of later onset and longer duration were associated with adverse outcomes. RELEVANCE TO CLINICAL PRACTICE: Hospital staff should pay attention to hypoactive delirium, take measures properly to decrease the severity and duration of delirium to improve the results of delirious patients. PMID- 26814371 TI - Corrigendum: Pyruvate Dehydrogenase Kinase 4 Promotes Vascular Calcification via SMAD1/5/8 Phosphorylation. PMID- 26814373 TI - Anguilla anguilla intestinal immune response to natural infection with Contracaecum rudolphii A larvae. AB - The European eel, Anguilla anguilla, is a major warm-water fish species cultured in North and South Europe. Seventy-one A. anguilla collected between 2010 and 2015 from the Comacchio lagoons were examined. Fish were infected and damaged by larvae (L3) of the nematode Contracaecum rudolphii A, which were encapsulated within the thickness of the intestinal wall and within the external visceral peritoneum (serosa). Conspicuous granulomas, visible at sites of infection, were arranged in a trilayer, formed by a series of concentric whorls. The cells involved in the immune response and their distribution in the granuloma layers were assessed by immunohistochemical, immunofluorescence, and ultrastructural techniques. The outer part of the granuloma contained macrophages, macrophage aggregates, and mast cells (MCs) scattered among fibroblasts. This layer was vascularized, with degranulation of MCs occurring in close proximity to the capillaries. The middle layer was rich in MCs and fibroblasts. The inner layer, closest to the parasite larva, consisted mainly of dark epithelioid cells, some of which were necrotic. Non-necrotic epithelioid cells formed desmosomes between themselves or with fibroblasts. Within the granulomas, numerous cells of different types were positive to proliferative cell nuclear antigen antibody, indicating a high degree of cellular proliferation around the larvae. PMID- 26814372 TI - HIV Susceptibility of human antigen-specific CD4 T cells in AIDS pathogenesis and vaccine response. AB - HIV causes infection and progressive depletion of human CD4 T cells. Emerging data have shown that antigen-specific CD4 T-cell subsets manifest differential susceptibility to HIV, potentially leading to pathogen-specific immune failure and opportunistic infections. This concept was recently explored in context of vectors utilized in HIV vaccine trials, and the data suggest that adenovirus type 5(Ad5)-specific CD4 T cells elicited by Ad5-HIV vaccine may be particularly susceptible to HIV, potentially rendering Ad5 vaccine recipients susceptible to HIV acquisition. We here examined recent data regarding the HIV susceptibility of antigen-specific CD4 T cells induced during infection or HIV vaccination and discussed its potential impact on HIV acquisition risk posed by HIV vaccination. PMID- 26814374 TI - How do nurses and ward managers perceive that evidence-based sources are obtained to inform relevant nursing interventions?--an exploratory study. AB - AIMS AND OBJECTIVES: To explore how nurses and managers perceive that evidence based sources are obtained to inform relevant nursing interventions. BACKGROUND: Implementation of evidence-based practice requires a systematic search and evaluation of research, clinical expertise and consideration of the patients' preferences and values. Much has been written over the past decade about how this should be done and nurses' mandatory education has provided them with the necessary tools to work in this way. In spite of this, nurses do not provide evidence-based practice on a regular basis. Many of the barriers against evidence based practice are dependent on contextual factors. Therefore, it can be of interest to study both managers and nurses. DESIGN: This qualitative study has an explorative and retrospective design. METHOD: Interviews were conducted with 15 participants, including eight nurses, four ward managers, two operation managers and one care developer. Directed content analysis was used. RESULT: Nurses and managers had different approaches towards the use of scientific knowledge. Nurses' use of clinical experience and learning from each other was common. Nurses' work as facilitators was structured by managers. Not involving the patient in the care was common among the nurses. CONCLUSION: The parts of evidence-based practice that are supported by the managers are also used by the nurses. When use of research is not controlled by the managers, the nurses do not search for scientific research. Neither is the patients' involvement in decision making obvious. RELEVANCE TO CLINICAL PRACTICE: A change in nurses' attitudes to scientific knowledge and perception of patient participation is needed. For this to happen, nurses need managers with a strong interest in evidence-based practice that support successful implementation of research in everyday clinical practise. PMID- 26814375 TI - Bone Mineral Density and Parathyroid Hormone as Independent Risk Factors for Mortality in Community-Dwelling Older Adults: A Population-Based Prospective Cohort Study in Brazil. The Sao Paulo Ageing & Health (SPAH) Study. AB - Previous studies have shown a relationship between osteoporosis and increased mortality risk. However, none of these studies performed a concomitant evaluation of the parathyroid hormone (PTH)-calcium-vitamin D axis and bone mass to accurately determine the contribution of each of these parameters to survival in older subjects. Thus, we sought to investigate the association between bone parameters and mortality in a longitudinal, prospective, population-based cohort of 839 elderly subjects. Clinical data (including history of fractures and cardiovascular events) were assessed using a specific questionnaire. Laboratory exams, including serum 25OHD and PTH, were also performed. Bone mineral density (BMD) at the lumbar spine and hip were evaluated using DXA. All analyses were performed at baseline (2005 to 2007). Mortality was recorded during follow-up. Multivariate Cox proportional regression was used to compute hazard ratios for all-cause and cardiovascular mortality. Over a mean 4.06 +/- 1.07 years, there were 132 (15.7%) deaths. These individuals were compared to 707 subjects who were alive at the end of the coverage period for mortality data collection. In a multivariate Cox proportional hazards model, age (HR 1.32; 95% CI, 1.13 to 1.55; p = 0.001, for each 5-year increase), male gender (HR 1.90; 95% CI, 1.30 to 2.79; p = 0.001), recurrent falls (more than two in the previous year; HR 1.65; 95% CI, 1.06 to 2.56; p = 0.026), diabetes mellitus (HR 2.17; 95% CI, 1.46 to 3.21; p < 0.001), low physical activity score (HR 1.78; 95% CI, 1.14 to 2.79; p = 0.011), prior cardiovascular event (HR 1.76; 95% CI, 1.18 to 2.63; p = 0.006), total hip BMD (HR 1.41; 95% CI, 1.15 to 1.72; p = 0.001, per each 1 SD decrease), and intact PTH (iPTH) (HR 1.06; 95% CI, 1.04 to 1.08; p < 0.001, per each 10 pg/mL increase) were independently associated with all-cause mortality. The subjects in the highest quartile of PTH (>49 pg/mL) were at a higher risk of cardiovascular death (HR 3.09; 95% CI, 1.36 to 6.99; p = 0.007) compared with the subjects in the lowest quartile (<26 pg/mL). Low BMD and higher PTH were significantly associated with mortality in community-dwelling older adults. These findings support the notion that careful screening of these bone parameters might lead to better management of older patients and improve outcomes in this population. (c) 2016 American Society for Bone and Mineral Research. PMID- 26814376 TI - Prevalence of Mycoplasma gallisepticum and Mycoplasma synoviae in commercial poultry, racing pigeons and wild birds in Belgium. AB - Mycoplasma gallisepticum is the most important pathogenic avian Mycoplasma species and causes chronic respiratory disease in poultry. In addition, the prevalence of Mycoplasma synoviae is of increasing concern in several EU member states. We investigated the prevalence of M. gallisepticum in commercial poultry (5220 layers, 1224 broilers and 1020 meat turkeys), 56 racing pigeons and 890 wild birds (Order Anseriformes, Galliformes, Pelecaniformes, Accipitriformes, Gruiformes, Charadriiformes, Columbiformes, Strigiformes, Falconiformes and Passeriformes). Broilers and wild birds were also evaluated for Mycoplasma synoviae. Dependent on the bird lifespan and the nature of the sample, different diagnostic tests were used including the rapid plate agglutination test, enzyme linked immunosorbent assay (ELISA), polymerase chain reaction and real-time polymerase chain reaction. A low prevalence of M. gallisepticum was found in both layers (0.9%; 95% CI: 0.7-1.2%) and broilers (2.7%; 95% CI: 1.9-3.8%) possibly due to reduced vertical transmission by breeder farms, which are under official surveillance. None of the samples from turkeys or racing pigeons tested positive. In wild birds, we found five birds were positive (1.7%; 95% CI: 0.7-3.9%): one wood pigeon, two grey herons, one mallard and one Eurasian magpie. For M. synoviae a high prevalence was found in broilers (12.9%: 95% CI: 11.1-14.9%). Four samples collected by hunters gave a positive result for M. synoviae (4%: 95% CI: 1.6-9.8%): one carrion crow and three wood pigeons. In addition, 12 house sparrows were found to be positive (3%; 95% CI: 1.7-5.2%). Wild birds probably play a limited role as a reservoir but we cannot exclude a possible impact on transmission of Mycoplasmas. PMID- 26814377 TI - Green Hospital and Climate Change: Their Interrelationship and the Way Forward. AB - Climate change is a reality, and the modern healthcare sector not just contributes towards this grave phenomenon but is itself being affected by it. The present review was thus conducted to understand the meaning of 'Green Hospital', to identify the many ways in which health sector is contributing towards climate change, to explore possibilities for countering this grave trend and last of all to look for institutions that are pioneering change. Data for the review was extracted from multiple online sources using the Google search engine. It was found that hospitals, being resource intensive establishments, consume vast amounts of electricity, water, food and construction materials to provide high quality care. It was also found that certain healthcare institutions, by employing simple, smart and sustainable measures can greatly reduce their environmental footprint. But constructing Green Hospitals can be a challenge considering the local conditions and growing customer expectations. PMID- 26814378 TI - Lean body mass as an independent determinant of dose-limiting toxicity and neuropathy in patients with colon cancer treated with FOLFOX regimens. AB - Evidence suggests that lean body mass (LBM) may be useful to normalize chemotherapy doses. Data from one prospective and one retrospective study were used to determine if the highest doses of oxaliplatin/kg LBM within FOLFOX regimens would be associated with dose-limiting toxicity (DLT) in colon cancer patients. Toxicity over four cycles was graded according to NCI Common Toxicity Criteria V2 or V3 (Common Terminology Criteria for Adverse Events, National Cancer Institute, Bethesda, MD). Muscle tissue was measured by computerized tomography (CT) and used to evaluate the LBM compartment of the whole body. In prospective randomized clinical trials conducted in France (n = 58), for patients given FOLFOX-based regimens according to body surface area, values of oxaliplatin/kg LBM were highly variable, ranging from 2.55 to 6.6 mg/kg LBM. A cut point of 3.09 mg oxaliplatin/kg LBM for developing toxicity was determined by Receiver Operating Characteristic (ROC) analysis, below this value 0/17 (0.0%) of patients experienced DLT; in contrast above this value 18/41 (44.0%) of patients were dose reduced or had treatment terminated owing to toxicity (>=Grade 3 or neuropathy >=Grade 2); for 9/41 the DLT was sensory neuropathy. These findings were validated in an independent cohort of colon cancer patients (n = 80) receiving FOLFOX regimens as part of standard care, in Canada. Low LBM is a significant predictor of toxicity and neuropathy in patients administered FOLFOX based regimens using conventional body surface area (BSA) dosing. PMID- 26814379 TI - Bioengineering and functional characterization of arenicin shortened analogs with enhanced antibacterial activity and cell selectivity. AB - New bioengineering approaches are required for development of more active and less toxic antimicrobial peptides. In this study we used beta-hairpin antimicrobial peptide arenicin-1 as a template for design of more potent antimicrobials. In particular, six shortened 17-residue analogs were obtained by recombinant expression in Escherichia coli. Besides, we have introduced the second disulfide bridge by analogy with the structure of tachyplesins. As a result, a number of analogs with enhanced activity and cell selectivity were developed. In comparison with arenicin-1, which acts on cell membranes with low selectivity, the most potent and promising its analog termed ALP1 possessed two fold higher antibacterial activity and did not affect viability of mammalian cells at concentration up to 50 MUM. The therapeutic index of ALP1 against both Gram-positive and Gram-negative bacteria was significantly increased compared with that of arenicin-1 while the mechanism of action remained the same. Like arenicin-1, the analog rapidly disrupt membranes of both stationary and exponential phase bacterial cells and effectively kills multidrug-resistant Gram negative bacteria. Furthermore, ALP1 was shown to bind DNA in vitro at a ratio of 1:1 (w/w). The circular dichroism spectra demonstrated that secondary structures of the shortened analogs were similar to that of arenicin-1 in water solution, but significantly differed in membrane-mimicking environments. This work shows that a strand length is one of the key parameters affecting cell selectivity of beta-hairpin antimicrobial peptides. PMID- 26814380 TI - Influence of Instruments Used in Root Canal Preparation on Amount of Apically Extruded Debris. AB - The aim of the present study was to compare the effects of ProTaper Gold, WaveOne Gold, ProTaper Universal, and WaveOne instruments on the amount of apically extruded debris. Eighty mandibular premolar teeth with straight root canals were selected and assigned to four groups (n = 20). The root canals were instrumented using ProTaper Gold, WaveOne Gold, ProTaper Universal, and WaveOne systems. Eppendorf tubes containing apically extruded debris were weighed three times, and mean values were calculated. The net mass of the extruded debris was calculated by subtracting the initial mass from the final mass. The groups were compared using one-way analysis of variance and Tukey's post hoc tests at a significance level of P < 0.05. The PTG group extruded less debris than the PTU group, and the WOG group extruded less debris than the WO group (P < 0.05). All the instrumentation systems tested in the present study were associated with apical extrusion of debris. PMID- 26814382 TI - Senear-Usher syndrome presenting with bipolar disorder: Management challenges. PMID- 26814381 TI - Pretreatment lymphopenia is an easily detectable predictive and prognostic marker in patients with metastatic esophagus squamous cell carcinoma receiving first line chemotherapy. AB - To explore the influence of pretreatment lymphopenia on the toxicity and efficacy of first-line chemotherapy in patients with metastatic esophagus squamous cell carcinoma (ESCC). In total, 215 patients were included in this retrospective study. Correlations between pretreatment lymphopenia (lymphocyte count <1 * 10(9) /L) and the occurrence of toxicity and the efficacy of first-line palliative chemotherapy were investigated. Pretreatment lymphopenia was found in 19.1% of the patients. The overall response rate (ORR) was 35.5% (65 of 183 patients). Patients with pretreatment lymphopenia had a lower ORR to chemotherapy compared with those without lymphopenia (22.2% vs. 38.8%, respectively; P = 0.045). Furthermore, the patients with pretreatment lymphopenia have higher grade 3-4 hematological toxicity than that of patients without pretreatment lymphopenia (19 of 41 patients, 46.3% vs. 54 of 174 patients, 31.0%; P = 0.048). Pretreatment lymphopenia was not correlated with grade 3-4 nonhematological toxicity. Multivariate analysis showed that pretreatment lymphopenia is an independent prognostic factor. Patients with pretreatment lymphopenia had a significantly shorter overall survival time than those without lymphopenia (8.2 months vs. 12.7 months; P = 0.020). This study shows that pretreatment lymphopenia is a good prognostic factor as well as a predictive factor for tumor response and chemotherapy-related hematological toxicity in metastatic ESCC. PMID- 26814384 TI - Systematic Reviews Keep Arthroscopy Up to Date. AB - Sometimes systematic reviews seem overprevalent, and some systematic reviews can be "inconclusive," which does not improve clinical decision making. On the other hand, systematic reviews can make a positive impact on patient outcomes by summarizing clinically relevant literature for arthroscopic surgeons and related researchers. PMID- 26814383 TI - Gap junction mediated miRNA intercellular transfer and gene regulation: A novel mechanism for intercellular genetic communication. AB - Intercellular genetic communication is an essential requirement for coordination of cell proliferation and differentiation and has an important role in many cellular processes. Gap junction channels possess large pore allowing passage of ions and small molecules between cells. MicroRNAs (miRNAs) are small regulatory RNAs that can regulate gene expression broadly. Here, we report that miRNAs can pass through gap junction channels in a connexin-dependent manner. Connexin43 (Cx43) had higher permeability, whereas Cx30 showed little permeability to miRNAs. In the tested connexin cell lines, the permeability to miRNAs demonstrated: Cx43 > Cx26/30 > Cx26 > Cx31 > Cx30 = Cx-null. However, consistent with a uniform structure of miRNAs, there was no significant difference in permeability to different miRNAs. The passage is efficient; the miRNA level in the recipient cells could be up to 30% of the donor level. Moreover, the transferred miRNA is functional and could regulate gene expression in neighboring cells. Connexin mutation and gap junctional blockers could eliminate this miRNA intercellular transfer and gene regulation. These data reveal a novel mechanism for intercellular genetic communication. Given that connexin expression is cell specific, this connexin-dependent, miRNA intercellular genetic communication may play an important role in synchronizing and coordinating proliferation and differentiation of specific cell types during multicellular organ development. PMID- 26814385 TI - Editorial Commentary: Long Head Biceps Pathology: How Do We Find It? AB - Identification of symptomatic long head biceps pathology continues to be a clinical challenge. Magnetic resonance imaging may fail to identify symptomatic lesions when present. Clinicians must maintain a high index of suspicion, and avoid over-reliance on diagnostic imaging in establishing a diagnosis or indicating surgery. PMID- 26814386 TI - Editorial Commentary: Subscapularis Tendon Tears--Do We Know What Our Preoperative Magnetic Resonance and Arthroscopic Images Are Showing? AB - Very little interobserver and intraobserver agreement is found when classifying and reclassifying magnetic resonance and arthroscopic images of subscapularis tendon tears. PMID- 26814387 TI - Biomechanical and Computed Tomography Analysis of Adjustable Femoral Cortical Fixation Devices for Anterior Cruciate Ligament Reconstruction in a Cadaveric Human Knee Model. AB - PURPOSE: To evaluate and compare two adjustable femoral cortical suspensory fixation devices used for anterior cruciate ligament reconstruction through a novel, direct computed tomography (CT) analysis metric and biomechanical laxity testing in a matched cadaveric human knee study. METHODS: Anterior cruciate ligament reconstructions with bovine tendon grafts were performed using two adjustable femoral cortical suspensory fixation devices (RigidLoop Adjustable [DePuy Synthes Mitek, Raynham, MA] and TightRope [Arthrex, Naples, FL]) in 12 knees (6 matched pairs). A mechanical testing series was used to determine each knee's laxity in the intact condition. After reconstruction, each specimen was again tested for laxity and also imaged with CT. The laxity testing and CT imaging were then repeated after 1,000 cycles of anteroposterior loading on each knee to compare changes in laxity for the two fixation devices and to visualize changes in button-to-graft distance migration through a three-dimensional CT imaging method. RESULTS: No significant differences were found between the two fixation groups' laxity measures after reconstruction (all P values >= .620) or after cycling (all P values >= .211) at any flexion angle. In addition, no significant differences were found between the two groups regarding button-to graft distance migration (P = .773; mean, 0.61 +/- 0.6 mm [95% confidence interval, -0.1 to 1.3 mm] in RigidLoop Adjustable group and 0.53 +/- 0.6 mm [95% confidence interval, -0.1 to 1.2 mm] in TightRope group). CONCLUSIONS: There were no significant differences between the two femoral cortical suspensory adjustable loop devices regarding laxity outcomes or loop displacement as measured by button to-graft distance migration. CLINICAL RELEVANCE: Use of either of the adjustable loop cortical suspensory devices in our analysis would appear to produce similar, acceptable laxity outcomes and minimal effects in terms of device-related loop displacement. PMID- 26814388 TI - Editorial Commentary: Controversy on Fixation Properties of the Adjustable-Loop Cortical Suspension Fixation Device Used for Anterior Cruciate Ligament Reconstruction. AB - Two adjustable-loop femoral cortical suspensory fixation devices tested in this cadaveric human knee study could afford comparably secure fixation properties under a cyclic loading condition. PMID- 26814389 TI - Editorial Commentary: Increase in Posterior Slope in High Tibial Osteotomy Is Preventable. AB - Increase in the posterior tibial slope after open-wedge high tibial osteotomy can be prevented by appropriate uniplanar and biplanar osteotomy with careful attention to osteotomy length and dimension of distraction. PMID- 26814390 TI - Editorial Commentary: There's No Time Like the Present if You Want to Save Your Mechanoreceptors! AB - The timing of stump-sparing surgery for the preservation of mechanoreceptors, volume of the anterior cruciate ligament stump, and number of Ruffini corpuscles matters, with longer delays leading to worse results for patients. PMID- 26814391 TI - Editorial Commentary: Combined High Tibial Osteotomy and Anterior Cruciate Ligament Reconstruction Yield Good Results With Unknown Effect of the Cartilage Restoration Procedure. AB - Realignment of the knee with high tibial osteotomy combined with anterior cruciate ligament reconstruction for a varus-deformed, anterior cruciate ligament deficient knee yields improved International Knee Documentation Committee functional outcomes at 1 and 5 years, with cartilage restoration shown by second look arthroscopy at 1 to 2 years. The effect of the cartilage restoration technique is still unknown, and recent literature poses a challenge to its need when realignment surgery is performed. PMID- 26814392 TI - Editorial Commentary: All-Inside or Inside-Out Meniscal Repair for the Posterior Thirds in Meniscus Allograft Transplantation? Which to Choose and What Difference It Makes. AB - Performing an all-inside repair or inside-out fixation for the posterior third in meniscus allograft transplantation is discussed. Less invasiveness is always important when the results are the same, and surgeons' personal experience may be a determining factor for this procedure. PMID- 26814393 TI - Editorial Commentary: Anterior Cruciate Ligament Remnant: What to Do With It? AB - There is considerable current controversy regarding surgical techniques for anterior cruciate ligament reconstruction. Yet despite constant evolution, clinical outcomes have changed very little. Subtle changes in surgical techniques are unlikely to have material impacts on patient-reported outcomes. PMID- 26814394 TI - Editorial Commentary: Reinventing the Anterior Cruciate Ligament. AB - Our goal as orthopaedic surgeons is to repair, reconstruct, and/or restore function and anatomy to our patients. A new study in this issue, commented upon here, represents another step toward helping surgeons recreate the anatomy of the native anterior cruciate ligament. PMID- 26814395 TI - Editorial Commentary: All-Inside Anterior Cruciate Ligament Reconstruction Can Afford Satisfactory Clinical Outcome and Functional Stability. AB - Anatomic all-inside anterior cruciate ligament reconstruction using the autogenous semitendinosus tendon graft can afford satisfactory outcomes, achieving significant postoperative improvement in all clinical parameters. PMID- 26814396 TI - Editorial Commentary: "All That Glitters Is Not Gold". AB - For the treatment of osteochondral lesions of the talus, the addition of concentrated bone marrow aspirate to marrow stimulation procedures results in repair tissue that, by magnetic resonance imaging, appears to be similar to native articular cartilage. But, functional outcomes are no different when compared with marrow stimulation alone. Moreover, the true "gold" is that the repair tissue not only has the magnetic resonance imaging appearance of native articular cartilage but also should have the same organizational structure and composition so that it may function like native articular cartilage. PMID- 26814397 TI - Editorial Commentary: Big Data Suggest That Because of a Significant Increased Risk of Postoperative Infection, Steroid Injection Is Not Recommended After Ankle Arthroscopy. AB - A recent study addressing infection rate after intra-articular steroid injection during ankle arthroscopy gives pause to this practice, with an odds ratio of 2.2 in the entire population that was injected with a steroid simultaneously with ankle arthroscopy compared with patients who did not receive an ankle injection. Big data, used in the study upon which the Editor comments here, suggest that because of a significant increased risk of postoperative infection, steroid injection is not recommended after ankle arthroscopy. PMID- 26814398 TI - Editorial Commentary: High-Tensile Strength Polyblend Tape Outperforms Suture for Whip and Krackow Stitch Models at Time Zero, Which Is No Surprise. AB - The matched, head-to-head comparison of high-tensile strength tape versus suture shows a higher load to failure for tape. This may be the first step to showing the advantage of polyblend tape in clinical models as we await further cyclic load testing to extend beyond time zero in cadaveric biomechanical modeling. PMID- 26814399 TI - Editorial Commentary: Open Versus Arthroscopic Biceps Tenodesis--You Choose. AB - In a Level IV evidence systematic review of 16 studies comparing arthroscopic and open biceps tenodesis, both techniques showed good or excellent short-term subjective and objective clinical outcomes in 98% of subjects. Ultimately, technique selection may be based on surgeon preference. In open tenodesis, one should avoid vigorous medial retraction to mitigate the risk of nerve injury. PMID- 26814400 TI - Editorial Commentary: Arthroscopic Debridement for Hip Dysplasia--The More Things Change, the More Things Stay the Same. AB - A systematic review of arthroscopic debridement versus open osteotomy for acetabular dysplasia documented essentially equivalent results; however, with much shorter follow-up and many fewer cases in the arthroscopic series. PMID- 26814401 TI - Editorial Commentary: Focal Cartilage Defect Matrix-Assisted Repair Has a Low Failure Rate. AB - Reported outcome of matrix-assisted cartilage treatment is 11% treatment failure at 5 years. On the other hand, the glass is more than half full, because 89% of patients do well at 5 years. Abrasion arthroplasty results in approximately 66% survivorship at 20 years; future cartilage restoration outcomes should prove more durable. PMID- 26814402 TI - Editorial Commentary: Well-Performed Anterior Cruciate Ligament Statistical Analysis Results in Figures Worth a Second Look. AB - Statisticians are required to ensure that systematic reviews and meta-analyses are performed using proper methods. Forest plots contain substantial and important information and are visually compelling, but conclusions could be incorrect absent appropriate application of statistical methods. PMID- 26814403 TI - Capturing in Vivo Plant Metabolism by Real-Time Analysis of Low to High Molecular Weight Volatiles. AB - We have deployed an efficient secondary electrospray ionization source coupled to an Orbitrap mass analyzer (SESI-MS) to investigate the emissions of a Begonia semperflorens. We document how hundreds of species can be tracked with an unparalleled time resolution of 2 min during day-night cycles. To further illustrate the capabilities of this system for volatile organic compounds (VOCs) analysis, we subjected the plant to mechanical damage and monitored its response. As a result, ~1200 VOCs were monitored displaying different kinetics. To validate the soundness of our in vivo measurements, we fully characterized some key compounds via tandem mass spectrometry (MS/MS) and confirmed their expected behavior based on prior gas chromatography/mass spectrometry (GC/MS) studies. For example, beta-caryophyllene, which is directly related to photosynthesis, was found to show a periodic day-night pattern with highest concentrations during the day. We conclude that the capability of SESI-MS to capture highly dynamic VOC emissions and wide analyte coverage makes it an attractive tool to complement GC/MS in plant studies. PMID- 26814404 TI - Articular cartilage vesicles and calcium crystal deposition diseases. AB - PURPOSE OF REVIEW: Articular cartilage vesicles (ACVs) are small extracellular vesicles that serve as foci of pathologic calcium crystal deposition in articular cartilage matrix. In this review, I have summarized the role of ACVs in calcium crystal formation and discuss recent findings that impact our understanding of the content, behavior, and origin of ACVs in healthy and diseased joints. The burgeoning interest in extracellular vesicles in other fields renders this a timely and relevant topic. RECENT FINDINGS: I have highlighted recent studies demonstrating that some ACVs originate in the autophagic pathway in healthy articular chondrocytes. I have reviewed accumulating evidence that nonmineralizing functions of ACVs contribute to osteoarthritis. I have also discussed new work supporting a role for extracellular vesicles in interleukin 1beta-induced mineralization and in mediating the catabolic effects of synovial inflammation in osteoarthritis. SUMMARY: We are making slow and steady progress in understanding the origin and function of ACVs and other relevant extracellular vesicles in arthritis. Further work in this interesting area is warranted. PMID- 26814405 TI - Microbiota and arthritis: correlations or cause? AB - PURPOSE OF REVIEW: The microorganisms that colonise our bodies, the commensal 'microbiota', respond to changes in our behaviour and environment, and can also profoundly affect our health. We can now investigate these organisms with unprecedented depth and precision, revealing that they may contribute to the pathogenesis of diseases including arthritis. Here we discuss the changes occurring in the microbiota in people with arthritis, and how manipulation of the microbiota may provide an additional pathway for therapy. RECENT FINDINGS: We highlight two important aspects of the recent literature. First we describe changes in the microbiota identified in people with arthritis; these correlations give insights into the microbial changes that may contribute to symptoms of arthritis. We then discuss attempts to ameliorate arthritis by manipulating the microbiota. This is a rapidly developing area of research. There are tantalising hints that interventions targeting the microbiota may become therapeutically viable for some types of inflammatory arthritis. SUMMARY: Our commensal microbial communities respond to changes in our health, and are altered in people with arthritis. Understanding the complex relationships between the microbiota and the body may enable us to deliberately manipulate these organisms and provide additional therapeutic options for people with arthritis. PMID- 26814407 TI - A novel allele HLA-A*11:152 was identified by sequence-based typing in a Chinese individual. AB - HLA-A*11:152 differs from A*11:01:01 by a single nucleotide at position 266 in Exon 2. PMID- 26814408 TI - Genomic full-length sequence of two HLA-A alleles, A*23:01:01 and A*24:02:01:01, identified by cloning and sequencing. AB - Genomic full-length sequences of HLA-A*23:01:01 and A*24:02:01:01, identified by cloning and sequencing from Chinese donors. PMID- 26814409 TI - Genomic full-length sequence of two HLA-A alleles, A*24:03:01 and A*24:07:01, identified by cloning and sequencing. AB - Genomic full length sequences of HLA-A*24:03:01 and A*24:07:01, identified by cloning and sequencing Chinese donors. PMID- 26814411 TI - The new HLA-A*24:321 shows one conservative amino acid replacement compared with HLA-A*24:02:01. AB - HLA-A*24:321 shows one nucleotide difference at codon 49 (GCG>GTG; A49>V49) compared with A*24:02:01. PMID- 26814410 TI - A further HLA-A*23 family allele--HLA-A*23:68. AB - HLA-A*23:68 differs from A*23:01:01 by one base (518C > A) in exon 3 resulting in an amino acid substitution of A149E. PMID- 26814412 TI - HLA-B*35:168, a novel HLA allele identified in a Chinese platelet donor. AB - HLA-B*35:168 has one nucleotide change from HLA-B*35:01:01:01 where 20 P is changed to R. PMID- 26814413 TI - HLA-B*40:306, a novel variant of HLA-B*40, discovered in a Taiwanese bone marrow hematopoietic stem cell donor. AB - One nucleotide substitution at residue 308 of the HLA-B*40:06:01:01 results in a new allele, HLA-B*40:306. PMID- 26814414 TI - A single nucleotide insertion in Exon 3 produces a novel HLA-B*58 null allele, HLA-B*58:72N. AB - One nucleotide insertion in Exon 3 of HLA-B*58:01:01:01 results in a new null allele, HLA-B*58:72N. PMID- 26814415 TI - A novel HLA-C null allele, HLA-C*08:121N. AB - HLA-C*08:121N results from two-nucleotide loss compared with its closest allele HLA-C*08:01:01. PMID- 26814416 TI - Correction of the HLA-DQB1*04:01:01 sequence at position 79 in exon 1. AB - The HLA-DQB1*04:01:01 sequence is corrected at position 79 in exon 1 (G > A, Ala > Thr). PMID- 26814417 TI - Description of a novel HLA-DQB1 allele, HLA-DQB1*06:126, in the Saudi stem cell donor registry. AB - HLA-DQB1*06:126 differs from HLA-DQB1*06:02:01 by a nonsynonymous C to T substitution at nucleotide position 1621 in Exon 2. PMID- 26814418 TI - A nucleotide insertion in Exon 2 is responsible for a new HLA-DRB1 null allele, HLA-DRB1*14:166N. AB - DRB1*14 is identical to DRB1*14:54:01 except for a single nucleotide insertion of A in position 175 in Exon 2. PMID- 26814419 TI - Increasing polymorphism of the RAET1E/ULBP4 gene in humans. AB - Description of three novel RAET1E/ULBP4 allele and promoter polymorphisms identified by sequence-based typing. PMID- 26814421 TI - High Fidelity, Efficiency and Functionalization of Ds-Px Unnatural Base Pairs in PCR Amplification for a Genetic Alphabet Expansion System. AB - Genetic alphabet expansion of DNA using an artificial extra base pair (unnatural base pair) could augment nucleic acid and protein functionalities by increasing their components. We previously developed an unnatural base pair between 7-(2 thienyl)-imidazo[4,5-b]pyridine (Ds) and 2-nitro-4-propynylpyrrole (Px), which exhibits high fidelity as a third base pair in PCR amplification. Here, the fidelity and efficiency of Ds-Px pairing using modified Px bases with functional groups, such as diol, azide, ethynyl and biotin, were evaluated by an improved method with optimized PCR conditions. The results revealed that all of the base pairs between Ds and either one of the modified Px bases functioned with high amplification efficiency (0.76-0.81), high selectivity (>=99.96% per doubling), and less sequence dependency, in PCR using 3'-exonuclease-proficient Deep Vent DNA polymerase. We also demonstrated that the azide-Px in PCR-amplified DNA was efficiently modified with any functional groups by copper-free click reaction. This genetic alphabet expansion system could endow nucleic acids with a wide variety of increased functionalities by the site-specific incorporation of modified Px bases at desired positions in DNA. PMID- 26814422 TI - Bi2MoO6/BiVO4 heterojunction electrode with enhanced photoelectrochemical properties. AB - Herein, we demonstrate the synthesis of a Bi2MoO6 nanorod array followed by the deposition of a BiVO4 absorber layer. This heterojunction yielded a photocurrent density of 250 MUA cm(-2) at 0.8 VSCE, which is 21 times that produced by a planar Bi2MoO6 array under the same conditions. Moreover, in situ X-ray photoelectron spectroscopy clearly confirmed the improvement of the electron transport and charge separation afforded by the heterostructure, features that efficiently enhanced the photoelectrochemical properties of the array. PMID- 26814420 TI - COMADRE: a global data base of animal demography. AB - The open-data scientific philosophy is being widely adopted and proving to promote considerable progress in ecology and evolution. Open-data global data bases now exist on animal migration, species distribution, conservation status, etc. However, a gap exists for data on population dynamics spanning the rich diversity of the animal kingdom world-wide. This information is fundamental to our understanding of the conditions that have shaped variation in animal life histories and their relationships with the environment, as well as the determinants of invasion and extinction. Matrix population models (MPMs) are among the most widely used demographic tools by animal ecologists. MPMs project population dynamics based on the reproduction, survival and development of individuals in a population over their life cycle. The outputs from MPMs have direct biological interpretations, facilitating comparisons among animal species as different as Caenorhabditis elegans, Loxodonta africana and Homo sapiens. Thousands of animal demographic records exist in the form of MPMs, but they are dispersed throughout the literature, rendering comparative analyses difficult. Here, we introduce the COMADRE Animal Matrix Database, an open-data online repository, which in its version 1.0.0 contains data on 345 species world-wide, from 402 studies with a total of 1625 population projection matrices. COMADRE also contains ancillary information (e.g. ecoregion, taxonomy, biogeography, etc.) that facilitates interpretation of the numerous demographic metrics that can be derived from its MPMs. We provide R code to some of these examples. SYNTHESIS: We introduce the COMADRE Animal Matrix Database, a resource for animal demography. Its open-data nature, together with its ancillary information, will facilitate comparative analysis, as will the growing availability of databases focusing on other aspects of the rich animal diversity, and tools to query and combine them. Through future frequent updates of COMADRE, and its integration with other online resources, we encourage animal ecologists to tackle global ecological and evolutionary questions with unprecedented sample size. PMID- 26814423 TI - Coordinated augmentation of NFAT and NOD signaling mediates proliferative VSMC phenotype switch under hyperinsulinemia. AB - AIM: Although hyperglycemia has been demonstrated to play a significant role in the vascular disease associated with type 2 diabetes, the mechanisms underlying hyperinsulinemia mediated vascular dysfunction are not well understood. We have analyzed whether hyperinsulinemia could activate NFAT (Nuclear factor of activated T cells) signaling and thereby influence vascular smooth muscle cell (VSMC) migration and proliferation, a major event in the progression of atherosclerosis. METHODS AND RESULTS: Human aortic VSMCs upon chronic insulin treatment exhibited increased expression of NFATc1 both at the mRNA and protein levels. The mechanistic role of NFAT in VSMC migration and proliferation was examined using 11R-VIVIT, a cell permeable NFAT specific inhibitor, where it reduced the insulin effect on VSMC, which was further substantiated by over expression or silencing of NFATc1gene (p < 0.05). This study also report for the first time the role of NFAT in NOD (Nucleotide oligomerization domain) mediated innate immune signaling and its significance in insulin effect on VSMCs. mRNA expression of NOD was up regulated when cells were treated with insulin or ligands whereas pretreatment with 11R-VIVIT reversed this effect (p < 0.05). Our study uphold the clinical significance as we observed an increased mRNA expression of NFATc1 in monocytes isolated from patients with type 2 diabetes which correlated positively with insulin resistance and glycemic load (p < 0.05). DISCUSSION: This study suggests that targeted NFAT inhibition can be an effective strategy to coordinately quench insulin induced proliferative and inflammatory responses along with innate immunity alterations in vascular smooth muscle cells, which underlie atherosclerosis. PMID- 26814424 TI - Differential Isotope Labeling of 38 Dietary Polyphenols and Their Quantification in Urine by Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry. AB - A large number of polyphenols are consumed with the diet and may contribute to the prevention of chronic diseases such as cardiovascular diseases, diabetes, cancers, and neurodegenerative diseases. More comprehensive methods are needed to measure exposure to this complex family of bioactive plant compounds in epidemiological studies. We report here a novel method enabling the simultaneous measurement in urine of 38 polyphenols representative of the main classes and subclasses found in the diet. This method is based on differential (12)C-/(13)C isotope labeling of polyphenols through derivatization with isotopic dansyl chloride reagents and on the analysis of the labeled polyphenols by tandem mass spectrometry. This derivatization approach overcomes the need for costly labeled standards. Different conditions for enzyme hydrolysis of polyphenol glucuronides and sulfate esters, extraction, and dansylation of unconjugated aglycones were tested and optimized. Limits of quantification varied from 0.01 to 1.1 MUM depending on polyphenols. Intrabatch coefficients of variation varied between 3.9% and 9.6%. Interbatch variations were lower than 15% for 31 compounds and lower than 29% for 6 additional polyphenols out of the 38 tested. Thirty seven polyphenols were validated and then analyzed in 475, 24 h urine samples from the European Prospective Investigation on Cancer and Nutrition (EPIC) study. Thirty four polyphenols could be detected and successfully estimated and showed large interindividual variations of concentrations (2-3 orders of magnitude depending on the compound), with median concentrations spanning from 0.01 to over 1000 MUM for all 34 compounds. PMID- 26814425 TI - Relationship between Travel Time from Home to a Regional Sleep Apnea Clinic in British Columbia, Canada, and the Severity of Obstructive Sleep. AB - RATIONALE: In the majority of people with obstructive sleep apnea, the disorder remains undiagnosed. This may be partly a result of inadequate access to diagnostic sleep services. We thus hypothesized that even modest travel times to a sleep clinic may delay diagnosis and reduce detection of milder disease. OBJECTIVES: We sought to determine whether travel time between an individual's home and a sleep clinic is associated with sleep apnea severity at presentation. METHODS: We recruited patients referred for suspected sleep apnea to the University of British Columbia Hospital Sleep Clinic between May 2003 and July 2011. The patient's place of residence was geocoded at the postal code level. Travel times between the population-weighted dissemination areas for each patient and the sleep clinic were calculated using ArcGIS (ESRI, Redlands, CA) network analyst and the Origin-Destination matrix function. All patients underwent full polysomnography. MEASUREMENTS AND MAIN RESULTS: There were 1,275 patients; 69% were male, the mean age was 58 years. (SD = 11.9), and the mean apnea-hypopnea index was 22 per hour (SD = 21.6). In the univariate model, travel time was a significant predictor of obstructive sleep apnea severity (P = 0.02). After controlling for confounders including sex, age, obesity, and education, travel time remained a significant predictor of sleep apnea severity (P < 0.01). In the multivariate model, each increase in 10 minutes of travel time was associated with an increase in the apnea-hypopnea index of 1.4 events per hour. CONCLUSIONS: For reasons that remain to be determined, travel times are associated with the severity of obstructive sleep apnea at presentation to a sleep clinic. If the results can be verified at other centers, this may help guide the geographic distribution of sleep centers within a health care system. PMID- 26814426 TI - Schima superba outperforms other tree species by changing foliar chemical composition and shortening construction payback time when facilitated by shrubs. AB - A 3.5-year field experiment was conducted in a subtropical degraded shrubland to assess how a nurse plant, the native shrub Rhodomyrtus tomentosa, affects the growth of the target trees Pinus elliottii, Schima superba, Castanopsis fissa, and Michelia macclurei, and to probe the intrinsic mechanisms from leaf chemical composition, construction cost (CC), and payback time aspects. We compared tree seedlings grown nearby shrub canopy (canopy subplots, CS) and in open space (open subplots, OS). S. superba in CS showed greater growth, while P. elliottii and M. macclurei were lower when compared to the plants grown in the OS. The reduced levels of high-cost compounds (proteins) and increased levels of low-cost compounds (organic acids) caused reduced CC values for P. elliottii growing in CS. While, the levels of both low-cost minerals and high-cost proteins increased in CS such that CC values of S. superba were similar in OS and CS. Based on maximum photosynthetic rates, P. elliottii required a longer payback time to construct required carbon in canopy than in OS, but the opposite was true for S. superba. The information from this study can be used to evaluate the potential of different tree species in the reforestation of subtropical degraded shrublands. PMID- 26814427 TI - Excitation wavelength-dependent EPR study on the influence of the conformation of multiporphyrin arrays on triplet state delocalization. AB - The optoelectronic properties of conjugated porphyrin arrays render them excellent candidates for use in a variety of molecular electronic devices. Understanding the factors controlling the electron delocalization in these systems is important for further developments in this field. Here, we use transient EPR and ENDOR (Electron Nuclear Double Resonance) to study the extent of electronic delocalization in the photoexcited triplet states of a series of butadiyne-linked porphyrin oligomers. We are able to distinguish between planar and twisted arrangements of adjacent porphyrin units, as the different conformations are preferentially excited at different wavelengths in the visible range. We show that the extent of triplet state delocalization is modulated by the torsional angle between the porphyrins and therefore by the excitation wavelength. These results have implications for the design of supramolecular systems with fine-tuned excitonic interactions and for the control of charge transport. PMID- 26814428 TI - Trends in Long-Term Outcomes Among Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Renal Disease. AB - OBJECTIVE: It is still not clear how advances in the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have impacted long-term outcomes. We undertook this study to examine changes over 25 years in long-term clinical outcomes, including the impact of renal function at diagnosis (a potential marker of time to disease detection) and the duration of cyclophosphamide use in AAV patients with renal involvement. METHODS: We included ANCA-positive patients with biopsy-proven AAV diagnosed between 1985 and 2009 who were followed up in the Glomerular Disease Collaborative Network inception cohort. Outcomes included the composite outcome of end-stage renal disease (ESRD) or death as well as relapse. Cox proportional hazards or competing risks regression models were adjusted for potential baseline confounders. RESULTS: Data from 554 patients were included in the analysis. There was a decreasing 5-year risk of ESRD or death over time (P < 0.001 by log rank test for trend). After adjustment for baseline characteristics, the risk of relapse was similar across the time periods (P = 0.45 by test for trend). Serum creatinine level at baseline was the only significant predictor of an increased risk of ESRD or death (hazard ratio 1.11 per 1 mg/dl of serum creatinine [95% confidence interval 1.04-1.18], P = 0.002). CONCLUSION: In patients with renal disease secondary to AAV, over 25 years the risk of ESRD or death has decreased but the risk of relapse has not changed. A higher serum creatinine level at diagnosis is associated with a higher risk of ESRD or death, suggesting that earlier disease detection is potentially an important measure to improve outcomes in AAV. PMID- 26814429 TI - Sustained Transmission of Pertussis in Vaccinated, 1-5-Year-Old Children in a Preschool, Florida, USA. PMID- 26814430 TI - A novel small molecule agent displays potent anti-myeloma activity by inhibiting the JAK2-STAT3 signaling pathway. AB - The oncogenic STAT3 signaling pathway is emerging as a promising target for the treatment of multiple myeloma (MM). In the present study, we identified a novel STAT3 inhibitor SC99 in a target-based high throughput screen. SC99 inhibited JAK2-STAT3 activation but had no effects on other transcription factors such as NF-kappaB, and kinases such as AKT, ERK, and c-Src that are in association with STAT3 signaling pathway. Furthermore, SC99 downregulated the expression of STAT3 modulated genes, including Bcl-2, Bcl-xL, VEGF, cyclin D2, and E2F-1. By inhibiting the STAT3 signaling, SC99 induced MM cell apoptosis which could be partly abolished by the ectopic expression of STAT3. Furthermore, SC99 displayed potent anti-MM activity in two independent MM xenograft models in nude mice. Oral administration of SC99 led to marked decrease of tumor growth within 10 days at a daily dosage of 30 mg/kg, but did not raise toxic effects. Taken together, this study identified a novel oral JAK2/STAT3 inhibitor that could be developed as an anti-myeloma agent. PMID- 26814431 TI - Fatty acid activated PPARgamma promotes tumorigenicity of prostate cancer cells by up regulating VEGF via PPAR responsive elements of the promoter. AB - In previous work, it is suggested that the excessive amount of fatty acids transported by FABP5 may facilitate the malignant progression of prostate cancer cells through a FABP5-PPARgamma-VEGF signal transduction axis to increase angiogenesis. To further functionally characterise the FABP5-PPARgamma-VEGF signal transduction pathway, we have, in this work, investigated the molecular mechanisms involved in its tumorigenicity promoting role in prostate cancer. Suppression of PPARgamma in highly malignant prostate cancer cells produced a significant reduction (up to 53%) in their proliferation rate, invasiveness (up to 89%) and anchorage-independent growth (up to 94%) in vitro. Knockdown of PPARgamma gene in PC3-M cells by siRNA significantly reduced the average size of tumours formed in nude mice by 99% and tumour incidence by 90%, and significantly prolonged the latent period by 3.5 fold. Results in this study combined with some previous results suggested that FABP5 promoted VEGF expression and angiogenesis through PPARgamma which was activated by fatty acids transported by FABP5. Further investigations showed that PPARgamma up-regulated VEGF expression through acting with the PPAR-responsive elements in the promoter region of VEGF gene in prostate cancer cells. Although androgen can modulate VEGF expression through Sp1/Sp3 binding site on VEGF promoter in androgen-dependent prostate cancer cells, this route, disappeared as the cells gradually lost their androgen dependency; was replaced by the FABP5-PPARgamma-VEGF signalling pathway. These results suggested that the FABP5-PPARgamma-VEGF signal transduction axis, rather than androgen modulated route, may be a more important novel therapeutic target for angiogenesis-suppression treatment of castration resistant prostate cancer. PMID- 26814432 TI - Paracrine effect of GTP cyclohydrolase and angiopoietin-1 interaction in stromal fibroblasts on tumor Tie2 activation and breast cancer growth. AB - Cancer-associated fibroblasts (CAFs) play a key role in promoting tumor growth, acting through complex paracrine regulation. GTP cyclohydrolase (GTPCH) expression for tetrahydrobiopterin synthesis in tumor stroma is implicated in angiogenesis and tumor development. However, the clinical significance of GTPCH expression in breast cancer is still elusive and how GTPCH regulates stromal fibroblast and tumor cell communication remains unknown. We found that GTPCH was upregulated in breast CAFs and epithelia, and high GTPCH RNA was significantly correlated with larger high grade tumors and worse prognosis. In cocultures, GTPCH expressing fibroblasts stimulated breast cancer cell proliferation and motility, cancer cell Tie2 phosphorylation and consequent downstream pathway activation. GTPCH interacted with Ang-1 in stromal fibroblasts and enhanced Ang-1 expression and function, which in turn phosphorylated tumor Tie2 and induced cell proliferation. In coimplantation xenografts, GTPCH in fibroblasts enhanced tumor growth, upregulating Ang-1 and alpha-smooth muscle actin mainly in fibroblast like cells. GTPCH inhibition resulted in the attenuation of tumor growth and angiogenesis. GTPCH/Ang-1 interaction in stromal fibroblasts and activation of Tie2 on breast tumor cells could play an important role in supporting breast cancer growth. GTPCH may be an important mechanism of paracrine tumor growth and hence a target for therapy in breast cancer. PMID- 26814434 TI - Medical Machiavellianism: the tradeoff between benefit and harm with targeted chemotherapy. AB - Machiavellianism is a word synonymous with the phrase "the end justifies the means", and in this article we have coined the term Medical Machiavellianism to describe the 'cruel-to-be-kind' administration of toxic chemotherapeutic agents in apparent violation of the precept first do no harm, while acknowledging the 'dirty hands' dilemma of having to decide between and choose the lesser of two evils in the setting of advanced cancer--i.e. to treat or not to treat. The perception that 'targeted' therapies are relatively non-toxic and therefore respect the Hippocratic First Commandment by virtue of their narrow selectivity is belied by their often inherent promiscuity, addressing multiple targets either inadvertently or deliberately, which may result in multiple side effects. The remarkable success of immunotherapy may have taken the bloom off the 'targeted agent' rose, however due to a lack of other approved treatment alternatives the toxicity of these agents may be overlooked or, at least, undervalued, especially given that the official measure of treatment success in oncology is overall survival (OS), not quality-of-life improvements. By analogy with the MACH-IV personality survey (1970), [1] which measures high and low Machiavellian orientation, we have defined in this article a rudimentary MACH scale for selected targeted chemotherapies, based on the means-to-ends ratio of toxicity and benefit. It is our hope that this comparison between targeted agents will itself function as a means to an end--to help oncologists strike the right balance between efficacy, toxicity and quality of life in the management of their patients. PMID- 26814433 TI - Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry. AB - BACKGROUND: Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score>=4+4 prostate cancer (PCa) in a manner independent of PSA. PATIENTS AND METHODS: Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/uL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naive, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. RESULTS: PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score>=8 disease, a high-risk prognostic factor, from patients with Gleason Score<=7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. CONCLUSIONS: PMP enumeration was able to identify patients with Gleason Score >=8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer. PMID- 26814435 TI - Common and distinct features of mammary tumors driven by Pten-deletion or activating Pik3ca mutation. AB - PTEN loss and PIK3CA activation both promote the accumulation of phosphatidylinositol (3, 4, 5)-trisphosphate (PIP3). While these proteins also have distinct biochemical functions, beyond the regulation of PIP3, little is known about the consequences of these differences in vivo. Here, we directly compared cancer signalling in mammary tumors from MMTV-Cre:Ptenf/f and MMTV Cre:Pik3ca(LSL-H1047R) mice. Using unsupervised hierarchical clustering we found that whereas MMTV-Cre:Pik3ca(LSL-H1047R)-derived tumors fall into two separate groups, designated squamous-likeEx and class14(Ex), MMTV-Cre:Ptenf/f tumors cluster as one group together with PIK3CA(H1047R) class14(Ex), exhibiting a 'luminal' expression profile. Gene Set Enrichment Analysis (GSEA) of Pten(Delta)?? and PIK3CA(H1047R) class14(Ex) tumors revealed very similar profiles of signalling pathways as well as some interesting differences. Analysis of 18 signalling signatures revealed that PI3K signalling is significantly induced whereas EGFR signalling is significantly reduced in Pten(?) versus PIK3CA(H1047R) tumors. Thus, Pten(?) and PIK3CA(H1047R) tumors exhibit discernable differences that may impact tumorigenesis and response to therapy. PMID- 26814437 TI - Reply. PMID- 26814436 TI - Dual PI-3 kinase/mTOR inhibition impairs autophagy flux and induces cell death independent of apoptosis and necroptosis. AB - The PI-3 kinase (PI-3K)/mTOR pathway is critical for cell growth and proliferation. Strategies of antagonising this signaling have proven to be detrimental to cell survival. This observation, coupled with the fact many tumours show enhanced growth signaling, has caused dual inhibitors of PI-3K and mTOR to be implicated in cancer treatment, and have thus been studied across various tumour models. Since PI-3K (class-I)/mTOR pathway negatively regulates autophagy, dual inhibitors of PI-3K/mTOR are currently believed to be autophagy activators. However, our present data show that the dual PI-3K/mTOR inhibition (DKI) potently suppresses autophagic flux. We further confirm that inhibition of Vps34/PI3KC3, the class-III PI-3K, causes the blockade to autophagosome-lysosome fusion. Our data suggest that DKI induces cell death independently of apoptosis and necroptosis, whereas autophagy perturbation by DKI may contribute to cell death. Given that autophagy is critical in cellular homeostasis, our study not only clarifies the role of a dual PI-3K/mTOR inhibitor in autophagy, but also suggests that its autophagy inhibition needs to be considered if such an agent is used in cancer chemotherapy. PMID- 26814438 TI - Biomechanical Analysis of Implanted Clavicle Hook Plates With Different Implant Depths and Materials in the Acromioclavicular Joint: A Finite Element Analysis Study. AB - Clinical implantation of clavicle hook plates is often used as a treatment for acromioclavicular joint dislocation. However, it is not uncommon to find patients that have developed acromion osteolysis or had peri-implant fracture after hook plate fixation. With the aim of preventing complications or fixation failure caused by implantation of inappropriate clavicle hook plates, the present study investigated the biomechanics of clavicle hook plates made of different materials and with different hook depths in treating acromioclavicular joint dislocation, using finite element analysis (FEA). This study established four parts using computer models: the clavicle, acromion, clavicle hook plate, and screws, and these established models were used for FEA. Moreover, implantations of clavicle hook plates made of different materials (stainless steel and titanium alloy) and with different depths (12, 15, and 18 mm) in patients with acromioclavicular joint dislocation were simulated in the biomechanical analysis. The results indicate that deeper implantation of the clavicle hook plate reduces stress on the clavicle, and also reduces the force applied to the acromion by the clavicle hook plate. Even though a clavicle hook plate made of titanium alloy (a material with a lower Young's modulus) reduces the force applied to the acromion by the clavicle hook plate, slightly higher stress on the clavicle may occur. The results obtained in this study provide a better reference for orthopedic surgeons in choosing different clavicle hook plates for surgery. PMID- 26814439 TI - Preparation and Characterization of Nanocomposites from Whey Protein Concentrate Activated with Lycopene. AB - The production and characterization of nanocomposites based on whey protein concentrate (WPC) and montmorilonite (MMT) incorporated with lycopene as a functional substance is presented and discussed as an alternative biomaterial for potential uses in foodstuff applications. A full factorial design with varying levels of MMT (0% and 2% in w/w) and lycopene (0%, 6%, and 12% in w/w) was used. Color, light transmission, film transparency, moisture, density, solubility, water vapor permeability, and antioxidant activity of the resulting materials were evaluated. Results indicated that lycopene and MMT nanoparticles were successfully included in WPC films using the casting/evaporation method. Inclusion of 2% w/w of MMT in the polymeric matrix significantly improved barrier property against water vapor. Lycopene, besides its good red coloring ability, provided to the films antioxidant activity and UV-vis light protection. These findings open a new perspective for the use of materials for bioactive packaging applications. PMID- 26814440 TI - Developing Statistical Models to Assess Transplant Outcomes Using National Registries: The Process in the United States. AB - Created by the US National Organ Transplant Act in 1984, the Scientific Registry of Transplant Recipients (SRTR) is obligated to publicly report data on transplant program and organ procurement organization performance in the United States. These reports include risk-adjusted assessments of graft and patient survival, and programs performing worse or better than expected are identified. The SRTR currently maintains 43 risk adjustment models for assessing posttransplant patient and graft survival and, in collaboration with the SRTR Technical Advisory Committee, has developed and implemented a new systematic process for model evaluation and revision. Patient cohorts for the risk adjustment models are identified, and single-organ and multiorgan transplants are defined, then each risk adjustment model is developed following a prespecified set of steps. Model performance is assessed, the model is refit to a more recent cohort before each evaluation cycle, and then it is applied to the evaluation cohort. The field of solid organ transplantation is unique in the breadth of the standardized data that are collected. These data allow for quality assessment across all transplant providers in the United States. A standardized process of risk model development using data from national registries may enhance the field. PMID- 26814441 TI - Functionalized graphene oxide serves as a novel vaccine nano-adjuvant for robust stimulation of cellular immunity. AB - Benefiting from their unique physicochemical properties, graphene derivatives have attracted great attention in biomedicine. In this study, we carefully engineered graphene oxide (GO) as a vaccine adjuvant for immunotherapy using urease B (Ure B) as the model antigen. Ure B is a specific antigen for Helicobacter pylori, which is a class I carcinogen for gastric cancer. Polyethylene glycol (PEG) and various types of polyethylenimine (PEI) were used as coating polymers. Compared with single-polymer modified GOs (GO-PEG and GO PEI), certain dual-polymer modified GOs (GO-PEG-PEI) can act as a positive modulator to promote the maturation of dendritic cells (DCs) and enhance their cytokine secretion through the activation of multiple toll-like receptor (TLR) pathways while showing low toxicity. Moreover, this GO-PEG-PEI can serve as an antigen carrier to effectively shuttle antigens into DCs. These two advantages enable GO-PEG-PEI to serve as a novel vaccine adjuvant. In the subsequent in vivo experiments, compared with free Ure B and clinically used aluminum-adjuvant-based vaccine (Alum-Ure B), GO-PEG-PEI-Ure B induces stronger cellular immunity via intradermal administration, suggesting promising applications in cancer immunotherapy. Our work not only presents a novel, highly effective GO-based vaccine nano-adjuvant, but also highlights the critical roles of surface chemistry for the rational design of nano-adjuvants. PMID- 26814442 TI - Risk factors for depression and fatigue among survivors of hematopoietic cell transplantation. AB - BACKGROUND: Patients treated with hematopoietic cell transplantation (HCT) often experience depression and fatigue but analyses to determine risk factors have typically lacked statistical power. The current study examined sociodemographic and clinical risk factors for depression and fatigue in a large cohort of survivors of HCT. METHODS: Measures of depression and fatigue were included in an annual survey of HCT recipients that also included self-reported sociodemographic and health information. Patient clinical characteristics were obtained from the clinical database. RESULTS: The sample consisted of 1869 recipients (with a mean age of 56 years; 53% male) who were a mean of 13 years (allogeneic recipients) and 6 years (autologous recipients) from HCT. Moderate to severe depression was reported by 13% of participants; moderate to severe fatigue was reported by 42%. Among allogeneic recipients, female sex, younger age, current presence of chronic pain, and current patient-reported severity of chronic graft-versus-host disease were found to be independently associated with greater depression whereas female sex, current presence of chronic pain, and current severity of chronic graft versus-host disease were independently associated with greater fatigue (P values <.01). Among autologous recipients, younger age and current presence of chronic pain were found to be independently associated with both greater depression and greater fatigue (P values <.01). CONCLUSIONS: Rates of depression and fatigue in this group of survivors suggest a high symptom burden. Better screening, referral, and interventions are needed. PMID- 26814443 TI - Sleep Disturbances in Childhood Cancer Survivors. PMID- 26814444 TI - Reply. PMID- 26814445 TI - Effect of variations of the complexity of the target variable on the assessment of Wiener-Granger causality in cardiovascular control studies. AB - We hypothesized that Wiener-Granger causality (WGC) indexes might have different abilities in coping with modifications of the complexity of the target variable in the context of the assessment of the cardiovascular control from spontaneous fluctuations of heart period (HP), systolic arterial pressure (SAP) and respiratory activity (R). After having defined the universe of knowledge as the set Omega = {HP, SAP, R} and the unpredictability decrement (UPD) as the difference between the prediction error variances of the target signal computed in Omega after excluding the presumed cause (i.e. the restricted Omega) and in Omega, we computed the following frequently utilized WGC indexes: (i) the plain UPD; (ii) the fractional UPD (FUPD) by dividing UPD by the prediction error variance in the restricted Omega; (iii) the normalized UPD (NUPD) by dividing UPD by the prediction error variance in Omega; (iv) the log-unpredictability decrement (LUPD) by applying the logarithm transformation to the prediction error variances before computing the UPD. The hypothesis was tested over two experimental protocols known to produce modifications of the complexity of HP variability: graded head-up tilt (HUT) inducing a gradual decrease of the HP complexity with tilt table inclination and head-down tilt (HDT) inducing the opposite trend. We demonstrated that: (1) when the strength of the causal relations from SAP to HP during HUT and from R to HP during HDT is assessed in Omega, WGC indexes reach different conclusions; (2) UPD is biased by modifications of the complexity of HP dynamics; (3) FUPD, NUPD and LUPD are less sensitive to changes of the complexity of the target dynamic, even though they have slightly different statistical power, being the NUPD the weakest one and FUPD and LUPD the strongest ones. We conclude that UPD should be avoided when assessing WGC and FUPD and LUPD should be privileged over NUPD. PMID- 26814446 TI - Adsorption of plasma proteins and fibronectin on poly(hydroxylethyl methacrylate) brushes of different thickness and their relationship with adhesion and migration of vascular smooth muscle cells. AB - The surface-grafted poly(hydroxylethyl methacrylate) (PHEMA) molecules were demonstrated to show a brush state regardless of their molecular length (molecular weight). Adsorption of proteins from 10% fetal bovine serum (FBS), fibronectin (Fn) and bovine serum albumin (BSA) was quantified by ellipsometry, revealing that the amounts of FBS and Fn decreased monotonously along with the increase of PHEMA thickness, whereas not detectable for BSA when the PHEMA thickness was larger than 6 nm. Radio immunoassay found that the adsorption of Fn from 10% FBS had no significant difference regardless of the PHEMA thickness. However, ELISA results showed that the Arg-Gly-Asp (RGD) activity of adsorbed Fn decreased with the increase of PHEMA thickness. By comparison of cellular behaviors of vascular smooth muscle cells (VSMCs) being cultured in vitro in the normal serum-containing medium and the Fn-depleted serum-containing medium, the significant role of Fn on modulating the adhesion and migration of VSMCs was verified. Taking account all the results, the Fn adsorption model and its role on linking the biomaterials surface to the VSMCs behaviors are proposed. PMID- 26814448 TI - Long-chain polynucleotide filler for skin rejuvenation: efficacy and complications in five patients. AB - Aging well has become the new target of preventative medicine, and aesthetic dermatology can contribute to this request. The polynucleotide (PN) containing products not only fill the space, but improve tissue regeneration, resulting in more natural tissue regeneration. Five Korean women received four times injections of long-chain PN filler in two-week intervals for skin rejuvenation. About 0.05 mL of material was injected in 40 points of one-side cheek. The pore and skin thickness were markedly improved in the patients in their 30s, whereas skin tone, melanin, wrinkles, and sagging were noticeably improved for patients in their 40s. There are no serious side effects. In conclusion, intradermal long chain PN filler injection seems to be an effective and safe treatment for skin rejuvenation. PMID- 26814449 TI - Delayed immunologic complications due to injectable fillers by unlicensed practitioners: our experiences and a review of the literature. AB - For a number of years, there have been unauthorized practitioners who have been illegally injecting substances. In this series of cases, delayed type hypersensitivity reactions occurred after having unknown material fillers injected by unlicensed practitioners. When injecting an unknown material, there can be a severe immune reaction due to the unknown number of antigens in the material, and therefore may act as a much stronger superantigen than conventional filler materials. It appears that the adverse effects in these cases are more severe and have tendency to break out after a longer period of time in comparison with those caused by approved fillers, likely due to operative technique and use of unverified materials. It is important to recognize the danger of such illegal procedures and to increase awareness of the public, as this has evolved into a significant public health issue. PMID- 26814452 TI - Prospective Validation of the Lupus Impact Tracker: A Patient-Completed Tool for Clinical Practice to Evaluate the Impact of Systemic Lupus Erythematosus. AB - OBJECTIVE: To evaluate the reliability, validity, responsiveness, and utility of the Lupus Impact Tracker (LIT). METHODS: This was a prospective longitudinal study with 20 North American sites participating. Consenting patients completed the LIT, Medical Outcomes Study Short Form 36 (version 2), Patient Health Questionnaire 9 (PHQ-9), LupusQoL, and patient LIT feedback questionnaire. Rheumatologists completed the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and physician LIT feedback questionnaire. The reliability, convergent validity, construct validity, and responsiveness of the LIT were evaluated. RESULTS: Of the 325 SLE patients enrolled, 90% were female, 53% were white, and 33% were African American. Their mean age was 42 years. The mean +/- SD baseline physician's global assessment and total SELENA SLEDAI scores were 1.04 +/- 0.8 and 4.28 +/- 3.8, respectively, while 3-month scores were 0.94 +/- 0.73 and 4.09 +/- 3.79, respectively. Internal consistency reliability was high (>0.9) at both visits. LIT scores correlated highly with other measures of patient-reported outcomes, and construct validity was established against clinical measures. The LIT was highly responsive to patient reported changes in SLE health status; however, LIT scores were not as responsive to changes in the SELENA-SLEDAI score. The majority of patients and physicians found LIT to be acceptable and feasible to administer in a clinical setting. CONCLUSION: The LIT is a reliable and valid instrument for assessing the impact of SLE on patients and captures unique and important information not included in physician assessments of disease. It may be useful in clinical practice to facilitate communication between the physician and the patient and enable efficient incorporation of the patient's perspective in disease management. PMID- 26814453 TI - High-contrast and fast electrochromic switching enabled by plasmonics. AB - With vibrant colours and simple, room-temperature processing methods, electrochromic polymers have attracted attention as active materials for flexible, low-power-consuming devices. However, slow switching speeds in devices realized to date, as well as the complexity of having to combine several distinct polymers to achieve a full-colour gamut, have limited electrochromic materials to niche applications. Here we achieve fast, high-contrast electrochromic switching by significantly enhancing the interaction of light--propagating as deep subwavelength-confined surface plasmon polaritons through arrays of metallic nanoslits, with an electrochromic polymer--present as an ultra-thin coating on the slit sidewalls. The switchable configuration retains the short temporal charge-diffusion characteristics of thin electrochromic films, while maintaining the high optical contrast associated with thicker electrochromic coatings. We further demonstrate that by controlling the pitch of the nanoslit arrays, it is possible to achieve a full-colour response with high contrast and fast switching speeds, while relying on just one electrochromic polymer. PMID- 26814454 TI - Simultaneous muscle water T2 and fat fraction mapping using transverse relaxometry with stimulated echo compensation. AB - Skeletal muscle inflammation/necrosis and fat infiltration are strong indicators of disease activity and progression in many neuromuscular disorders. They can be assessed by muscle T2 relaxometry and water-fat separation techniques, respectively. In the present work, we exploited differences between water and fat T1 and T2 relaxivities by applying a bi-component extended phase graph (EPG) fitting approach to simultaneously quantify the muscle water T2 and fat fraction from standard multi-slice multi-echo (MSME) acquisitions in the presence of stimulated echoes. Experimental decay curves were adjusted to the theoretical model using either an iterative non-negative least-squares (NNLS) procedure or a pattern recognition approach. Twenty-two patients (age, 49 +/- 18 years) were selected to cover a large range of muscle fat infiltration. Four cases of chronic or subchronic juvenile dermatomyositis (age, 8 +/- 3 years) were investigated before and 3 months following steroid treatment. For control, five healthy volunteers (age, 25 +/- 2 years) were recruited. All subjects underwent the MSME sequence and EPG fitting procedure. The EPG fitting algorithm allowed a precise estimation of water T2 and fat fraction in diseased muscle, even in the presence of large B1(+) inhomogeneities. In the whole cohort of patients, there was no overall correlation between water T2 values obtained with the proposed method and the fat fraction estimated inside muscle tissues (R(2) = 0.02). In the patients with dermatomyositis, there was a significant decrease in water T2 (-4.09 +/- 3.7 ms) consequent to steroid treatment. The pattern recognition approach resulted in a 20-fold decrease in processing time relative to the iterative NNLS procedure. The fat fraction derived from the EPG fitting approach correlated well with the fat fraction derived from a standard three-point Dixon method (~1.5% bias). The bi-component EPG fitting analysis is a precise tool to monitor muscle tissue disease activity and is able to handle bias introduced by fat infiltration and B1(+) inhomogeneities. PMID- 26814455 TI - The importance of daily removal of the denture biofilm for oral and systemic diseases prevention. PMID- 26814456 TI - Static compression regulates OPG expression in periodontal ligament cells via the CAMK II pathway. AB - OBJECTIVE: This study aimed to investigate the potential role of CAMK II pathway in the compression-regulated OPG expression in periodontal ligament cells (PDLCs). MATERIAL AND METHOds: The PDL tissue model was developed by 3-D culturing human PDLCs in a thin sheet of poly lactic-co-glycolic acid (PLGA) scaffolds, which was subjected to static compression of 25 g/cm2 for 3, 6 and 12 h, with or without treatment of KN-93. After that, the expression of OPG, RANKL and NFATC2 was investigated through real-time PCR and western blot analysis. RESULTS: After static compression, the NFATC2 and RANKL expression was significantly up-regulated, while partially suppressed by KN-93 for 6 and 12 h respectively. The OPG expression was significantly down-regulated by compression in 3 h, started to elevate in 6 h, and significantly up-regulated in 12 h. The up regulation after 12 h was significantly suppressed by KN-93. CONCLUSIONS: Long term static compression increases OPG expression in PDLCs, at least partially, via the CAMK II pathway. PMID- 26814457 TI - Deep pain sensitivity is correlated with oral-health-related quality of life but not with prosthetic factors in complete denture wearers. AB - Low pressure Pain Threshold (PPT) is considered a risk factor for Temporomandibular Disorders (TMD) and is influenced by psychological variables. Objectives To correlate deep pain sensitivity of masticatory muscles with prosthetic factors and Oral-Health-Related Quality of Life (OHRQoL) in completely edentulous subjects. Material and Methods A total of 29 complete denture wearers were recruited. The variables were: a) Pressure Pain Threshold (PPT) of the masseter and temporalis; b) retention, stability, and tooth wear of dentures; c) Vertical Dimension of Occlusion (VDO); d) Oral Health Impact Profile (OHIP) adapted to orofacial pain. The Kolmogorov-Smirnov test, the Pearson Product Moment correlation coefficient, the Spearman Rank correlation coefficient, the Point-Biserial correlation coefficient, and the Bonferroni correction (alpha=1%) were applied to the data. Results The mean age (standard deviation) of the participants was of 70.1 years (9.5) and 82% of them were females. There were no significant correlations with prosthetic factors, but significant negative correlations were found between the OHIP and the PPT of the anterior temporalis (r=-0.50, 95% CI-0.73 to 0.17, p=0.005). Discussion The deep pain sensitivity of masticatory muscles in complete dentures wearers is associated with OHRQoL, but not with prosthetic factors. PMID- 26814458 TI - Effect of 10% fluoride on the remineralization of dentin in situ. AB - Objective The purpose of this randomized, cross-over, in situ study was to determine the remineralization of demineralized dentin specimens after the application of a 10% fluoride (F-) or a 1% chlorhexidine-1% thymol (CHX-thymol) varnish. Material and Methods Twelve individuals without current caries activity wore removable appliances in the lower jaw for a period of four weeks. Each appliance contained four human demineralized dentin specimens fixed on the buccal aspects. The dentin specimens were obtained from the cervical regions of extracted human third molars. After demineralization, half the surface of each specimen was covered with a nail varnish to serve as the reference surface. The dentin specimens were randomly assigned to one of the three groups: F-, CHX thymol, and control (no treatment). Before the first treatment period and between the others, there were washout periods of one week. After each treatment phase, the changes in mineral content (vol% um) and the lesion depths (um) of the dentin slabs were determined by transverse microradiography (TMR). Data analysis was accomplished by the Kruskal-Wallis test and the Mann-Whitney U test (p<0.05). Results The medians (25th/75th percentile) of integrated mineral loss were 312.70 (203.0-628.7) for chlorhexidine varnish, 309.5 (109.8-665.8) for fluoride varnish, and -346.9 (-128.7 - -596.0) for the control group. The medians (25th/75th percentile) of lesion depth were 13.6 (5.7-34.5) for chlorhexidine varnish, 16.5 (5.6-38.1) for fluoride varnish, and -14.2 (-4.5- -32.9) for the control group. Use of the 10% F- or 1% CHX-1% thymol varnishes resulted in significantly decreased mineral loss and lesion depth in dentin when compared with the control group. There were no statistically significant differences among the test groups. Conclusions Within the limitations of this study, the results suggest that the effect of the treatment of demineralized dentin with 10% F- or 1% CHX-1% thymol is better than without any treatment. PMID- 26814459 TI - Pre-heating mitigates composite degradation. AB - Dental composites cured at high temperatures show improved properties and higher degrees of conversion; however, there is no information available about the effect of pre-heating on material degradation. Objectives This study evaluated the effect of pre-heating on the degradation of composites, based on the analysis of radiopacity and silver penetration using scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS). Material and Methods Thirty specimens were fabricated using a metallic matrix (2x8 mm) and the composites Durafill VS (Heraeus Kulzer), Z-250 (3M/ESPE), and Z-350 (3M/ESPE), cured at 25 degrees C (no pre-heating) or 60 degrees C (pre-heating). Specimens were stored sequentially in the following solutions: 1) water for 7 days (60 degrees C), plus 0.1 N sodium hydroxide (NaOH) for 14 days (60 degrees C); 2) 50% silver nitrate (AgNO3) for 10 days (60 degrees C). Specimens were radiographed at baseline and after each storage time, and the images were evaluated in gray scale. After the storage protocol, samples were analyzed using SEM/EDS to check the depth of silver penetration. Radiopacity and silver penetration data were analyzed using ANOVA and Tukey's tests (alpha=5%). Results Radiopacity levels were as follows: Durafill VSZ-350>Z-250 (p<0.05). After storage in water/NaOH, pre-heated specimens presented higher radiopacity values than non-pre heated specimens (p<0.05). There was a lower penetration of silver in pre-heated specimens (p<0.05). Conclusions Pre-heating at 60 degrees C mitigated the degradation of composites based on analysis of radiopacity and silver penetration depth. PMID- 26814460 TI - Differential expression of CC chemokines (CCLs) and receptors (CCRs) by human T lymphocytes in response to different Aggregatibacter actinomycetemcomitans serotypes. AB - In Aggregatibacter actinomycetemcomitans, different serotypes have been described based on LPS antigenicity. Recently, our research group has reported a differential immunogenicity when T lymphocytes were stimulated with these different serotypes. In particular, it was demonstrated that the serotype b of A. actinomycetemcomitans has a stronger capacity to trigger Th1- and Th17-type cytokine production. Objective This study aimed to quantify the expression of different CC chemokines (CCLs) and receptors (CCRs) in T lymphocytes stimulated with the different A. actinomycetemcomitans serotypes. In addition, the expression of the transcription factors T-bet, GATA-3, RORC2, and Foxp3, master switch genes implied in the Th1, Th2, Th17, and T-regulatory differentiation, respectively, was analyzed in order to determine T-cell phenotype-specific patterns of CCL and CCR expression upon A. actinomycetemcomitans stimulation. Material and Methods Human naive CD4+ T lymphocytes were obtained from healthy subjects and stimulated with autologous dendritic cells primed with the different A. actinomycetemcomitans serotypes. The expression levels for the chemokines CCL1, CCL2, CCL3, CCL5, CCL11, CCL17, CCL20, CCL21, CCL25, and CCL28, as well as the chemokine receptors CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 were quantified by qPCR. Similarly, the expression levels for the transcription factors T-bet, GATA-3, RORC2, and Foxp3 were quantified and correlated with the CCL and CCR expression levels. Results Higher expression levels of CCL2, CCL3, CCL5, CCL20, CCL21, CCL28, CCR1, CCR2, CCR5, CCR6, CCR7, and CCR9 were detected in T lymphocytes stimulated with the serotype b of A. actinomycetemcomitans compared with the other serotypes. In addition, these higher expression levels of CCLs and CCRs positively correlated with the increased levels of T-bet and RORC2 when T lymphocytes were stimulated with the serotype b. Conclusion A T-lymphocyte response biased towards a Th1- and Th17 pattern of CCL and CCR expression was detected under stimulation with the serotype b of A. actinomycetemcomitans. PMID- 26814461 TI - Cytocompatibility and biocompatibility of nanostructured carbonated hydroxyapatite spheres for bone repair. AB - OBJECTIVE: The aim of this study was to investigate the in vitro and in vivo biological responses to nanostructured carbonated hydroxyapatite/calcium alginate (CHA) microspheres used for alveolar bone repair, compared to sintered hydroxyapatite (HA). MATERIAL AND METHODS: The maxillary central incisors of 45 Wistar rats were extracted, and the dental sockets were filled with HA, CHA, and blood clot (control group) (n=5/period/group). After 7, 21 and 42 days, the samples of bone with the biomaterials were obtained for histological and histomorphometric analysis, and the plasma levels of RANKL and OPG were determined via immunoassay. Statistical analysis was performed by Two-Way ANOVA with post-hoc Tukey test at 95% level of significance. RESULTS: The CHA and HA microspheres were cytocompatible with both human and murine cells on an in vitro assay. Histological analysis showed the time-dependent increase of newly formed bone in control group characterized by an intense osteoblast activity. In HA and CHA groups, the presence of a slight granulation reaction around the spheres was observed after seven days, which was reduced by the 42nd day. A considerable amount of newly formed bone was observed surrounding the CHA spheres and the biomaterials particles at 42-day time point compared with HA. Histomorphometric analysis showed a significant increase of newly formed bone in CHA group compared with HA after 21 and 42 days from surgery, moreover, CHA showed almost 2-fold greater biosorption than HA at 42 days (two-way ANOVA, p<0.05) indicating greater biosorption. An increase in the RANKL/OPG ratio was observed in the CHA group on the 7th day. CONCLUSION: CHA spheres were osteoconductive and presented earlier biosorption, inducing early increases in the levels of proteins involved in resorption. PMID- 26814462 TI - Can a bleaching toothpaste containing Blue Covarine demonstrate the same bleaching as conventional techniques? An in vitro, randomized and blinded study. AB - OBJECTIVE: The purpose of this in vitro study was to compare the efficacy of a bleaching toothpaste containing Blue Covarine vs. conventional tooth bleaching techniques using peroxides (both in-office and at-home). MATERIAL AND METHODS: Samples were randomly distributed into five experimental groups (n=15): C - Control; BC - Bleaching toothpaste containing Blue Covarine; WBC - Bleaching toothpaste without Blue Covarine; HP35 - In-office bleaching using 35% hydrogen peroxide; and CP10 - At-home bleaching with 10% carbamide peroxide. The dental bleaching efficacy was determined by the color difference (DeltaE), luminosity (DeltaL), green-red axis (Deltaa), and blue-yellow axis (Deltab). The CIELab coordinates were recorded with reflectance spectroscopy at different times: T0 - baseline, T1 - immediately after bleaching, T2 - 7 days, T3 - 14 days, and T4 - 21 days after the end of treatments. Data were analyzed by a repeated measures mixed ANOVA and post hoc Bonferroni test, with a significance level of 5%. RESULTS: No significant differences were found between the treatment groups C, BC, and WBC. The groups HP35 and CP10 showed significantly higher whitening efficacy than groups C, BC, and WBC. CONCLUSIONS: There were no significant differences in the whitening efficacy between a Blue Covarine containing toothpaste, a standard whitening toothpaste, and a control. Neither of the whitening toothpastes tested were as effective as in-office or at-home bleaching treatments. PMID- 26814463 TI - Effects of plasma on polyethylene fiber surface for prosthodontic application. AB - Plasma technology has the potential to improve the adherence of fibers to polymeric matrices, and there are prospects for its application in dentistry to reinforce the dental particulate composite. Objectives This study aimed to investigate the effect of oxygen or argon plasma treatment on polyethylene fibers. MATERIAL AND METHODS: Connect, Construct, InFibra, and InFibra treated with oxygen or argon plasma were topographically evaluated by scanning electron microscopy (SEM), and chemically by X-ray photoelectron spectroscopy (XPS). For bending analysis, one indirect composite (Signum) was reinforced with polyethylene fiber (Connect, Construct, or InFibra). The InFibra fiber was subjected to three different treatments: (1) single application of silane, (2) oxygen or argon plasma for 1 or 3 min, (3) oxygen or argon plasma and subsequent application of silane. The samples (25x2x2 mm), 6 unreinforced and 60 reinforced with fibers, were subjected to three-point loading tests to obtain their flexural strength and deflection. The results were statistically analyzed with ANOVA and the Bonferroni correction for multiple comparison tests. RESULTS: SEM analysis showed that oxygen and argon plasma treatments promote roughness on the polyethylene fiber surface. X-ray photoelectron spectroscopy (XPS) analysis shows that both plasmas were effective in incorporating oxygenated functional groups. Argon or oxygen plasma treatment affected the flexural strength and deflection of a fiber reinforced composite. The application of silane does not promote an increase in the flexural strength of the reinforced composites. CONCLUSIONS: Oxygen and argon plasma treatments were effective in incorporating oxygenated functional groups and surface roughness. The highest strength values were obtained in the group reinforced with polyethylene fibers treated with oxygen plasma for 3 min. PMID- 26814464 TI - Effect of collagen sponge and fibrin glue on bone repair. AB - The ability of hemostatic agents to promote bone repair has been investigated using in vitro and in vivo models but, up to now, the results are inconclusive. Objective In this context, the aim of this study was to compare the potential of bone repair of collagen sponge with fibrin glue in a rat calvarial defect model. MATERIAL AND METHODS: Defects of 5 mm in diameter were created in rat calvariae and treated with either collagen sponge or fibrin glue; untreated defects were used as control. At 4 and 8 weeks, histological analysis and micro-CT-based histomorphometry were carried out and data were compared by two-way ANOVA followed by Student-Newman-Keuls test when appropriated (p<=0.05). RESULTS: Three dimensional reconstructions showed increased bone formation in defects treated with either collagen sponge or fibrin glue compared with untreated defects, which was confirmed by the histological analysis. Morphometric parameters indicated the progression of bone formation from 4 to 8 weeks. Additionally, fibrin glue displayed slightly higher bone formation rate when compared with collagen sponge. CONCLUSION: Our results have shown the benefits of using collagen sponge and fibrin glue to promote new bone formation in rat calvarial bone defects, the latter being discreetly more advantageous. PMID- 26814468 TI - Transmetallation from CCC-NHC pincer Zr complexes in the synthesis of air-stable CCC-NHC pincer Co(iii) complexes and initial hydroboration trials. AB - Development of CCC-NHC pincer Co complexes via transmetalation from Zr is reported. Formation of these air-stable Co(iii) complexes was achieved through use of a CoCl2 or Co(acac)3in situ or with a discrete CCC-NHC pincer Zr transmetallating agent. Preliminary activity in the hydroboration of styrene is reported. This facile methodology will further the development of CCC-NHC pincer first-row transition metal complexes. PMID- 26814465 TI - Effects of air abrasion with alumina or glass beads on surface characteristics of CAD/CAM composite materials and the bond strength of resin cements. AB - OBJECTIVE: The study aimed to evaluate effects of air abrasion with alumina or glass beads on bond strengths of resin cements to CAD/CAM composite materials. MATERIAL AND METHODS: CAD/CAM composite block materials [Cerasmart (CS) and Block HC (BHC)] were pretreated as follows: (a) no treatment (None), (b) application of a ceramic primer (CP), (c) alumina-blasting at 0.2 MPa (AB), (d) AB followed by CP (AB+CP), and (e) glass-beads blasting at 0.4 MPa (GBB) followed by CP (GBB+CP). The composite specimens were bonded to resin composite disks using resin cements [G-CEM Cerasmart (GCCS) and ResiCem (RC)]. The bond strengths after 24 h (TC 0) and after thermal cycling (TC 10,000 at 4-60 degrees C) were measured by shear tests. Three-way ANOVA and the Tukey compromise post hoc tests were used to analyze statistically significant differences between groups (alpha=0.05). RESULTS: For both CAD/CAM composite materials, the None group exhibited a significant decrease in bond strength after TC 10,000 (p<0.05). AB showed significantly higher bond strength after TC 10,000 than the None group, while CP did not (p<0.05). GBB exhibited smaller surface defects than did AB; however, their surface roughnesses were not significantly different (p>0.05). The AB+CP group showed a significantly higher bond strength after TC 10,000 than did the AB group for RC (p<0.05), but not for GCCS. The GBB+CP group showed the highest bond strength for both thermal cyclings (p<0.05). CONCLUSIONS: Air abrasion with glass beads was more effective in increasing bond durability between the resin cements and CAD/CAM composite materials than was using an alumina powder and a CP. PMID- 26814466 TI - Antimicrobial activity of complete denture cleanser solutions based on sodium hypochlorite and Ricinus communis - a randomized clinical study. AB - To preserve oral health and to maintain the prosthetic devices, it is important not only to improve the properties of commonly known hygiene products, but also to investigate new materials with antimicrobial action. Objectives This study evaluated the antimicrobial activity of sodium hypochlorite (0.25% and 0.50%) and 10% Ricinus communis' solutions against specific microorganisms. MATERIAL AND METHODS: Sixty four maxillary complete denture wearers were instructed to brush their dentures three times a day and to soak them (20 min/day) in the solutions: SH1: 0.25% sodium hypochlorite; SH2: 0.5% sodium hypochlorite; RC: 10% R. communis oil; and C: 0.85% saline (control). The solutions were used for 7 days in a randomized sequence. Following each period of use, there was a 1-week washout period. Antimicrobial activity was determined by Colony Forming Units (CFU) counts of Streptococcus mutans, Candida spp., and gram-negative microorganisms. For collecting biofilm, the internal surface of maxillary dentures was brushed with saline solution, and biofilm suspension obtained. After dilutions (100 - 10-3), aliquots were seeded in Mitis salivarius, CHROMagar Candida, and MacConkey agar for detecting S. mutans, Candida spp., or gram negative microorganisms, respectively. After incubation, colonies were counted, and CFU/mL values were calculated. Then, transformation - log10 (CFU+1) - data were analyzed using the Friedman test (alpha=0.05). Results showed significant differences between the solutions (p<0.001). RESULTS: All three solutions showed antimicrobial activity against S. mutans. Against Candida spp., RC and SH1 solutions showed similar effect while SH2 showed superior activity. SH1 and SH2 solutions showed antimicrobial action against gram-negative microorganisms. The Candida species most frequently isolated was C. albicans, followed by C. tropicalis and C. glabrata. CONCLUSIONS: The 0.5% sodium hypochlorite solution was the most effective and might be used to control denture biofilm. C. albicans was the most frequently isolated Candida sp. PMID- 26814469 TI - A Cross-Sectional Study on Pattern of Alcohol Consumption and Body Mass Index Among Health Institution Students in Bagalkot. AB - INTRODUCTION: Adolescence is a vulnerable period, where they try to initiate new things, sometimes wicked habits or high risk behaviours like smoking or alcohol consumption. Due to change in lifestyle a considerable number of social drinkers have shifted to heavy episodic drinking. Alcohol consumption plays a role in the development of obesity but the relationship between alcohol and weight is still unclear. OBJECTIVES: To find the association between pattern of drinking and Body Mass Index (BMI). MATERIALS AND METHODS: A cross-sectional study was conducted among 395 students from five health Institutions in Bagalkot. A pre tested, semi structured questionnaire was used and BMI was noted. Results were tabulated using Microsoft excel 2007 and analysis were performed using OpenEpi, version 2.3.1. Chi square tests was used to find the association. RESULTS: In the present study 68% were girls and 32% were boys. About one fifth (20.53%) were current alcohol drinkers. Alcohol quantity and frequency had inverse association with BMI. As quantity increases from 1 drink/drinking day to >=4 drinks/drinking day, BMI increases from 20.49 (95%CL 14.66-26.33) to 22.66 (95%CL 12.62-32.70). As frequency increased from low to high quintiles of drinking days/year, BMI significantly decreases (p <0.003) from 21.44 (95% CI 20.31-22.58) to 20.38 (95% CI 13.05-27.72). CONCLUSION: Alcohol contributes to increase in body weight in certain types of drinking pattern while in others it was not associated. PMID- 26814470 TI - Radical Monocationic Guanidino-Functionalized Aromatic Compounds (GFAs) as Bridging Ligands in Dinuclear Metal Acetate Complexes: Synthesis, Electronic Structure, and Magnetic Coupling. AB - In this work, the oxidation of several new dinuclear metal (M) acetate complexes of the redox-active guanidino-functionalized aromatic compound (GFA) 1,2,4,5 tetrakis(tetramethylguanidino)benzene (1) was studied. The complexes [1{M(OAc)2}2] (M = Ni or Pd) were oxidized to the radical monocationic complexes [1{M(OAc)2}2](+ *). From CV (cyclic voltammetry) measurements, the Gibbs free enthalpy for disproportionation of [1{M(OAc)2}2](+ *) into [1{M(OAc)2}2] and [1{M(OAc)2}2](2+) could be estimated to be roughly +20 kJ mol(-1) in CH2Cl2 solution. A characteristic feature of the [1{M(OAc)2}2](+ *) complexes is the presence of intense metal-ligand charge-transfer bands in the electronic absorption spectra. The complex [1{Ni(OAc)2}2](+ *) combines three paramagnetic centers with four metal-centered unpaired electrons and a ligand centered pi radical and exhibits a sextet electronic ground state. Spin distribution of the Ni complexes was evaluated by paramagnetic (1)H and (13)C NMR and was correlated with calculations. The strong ferromagnetic metal-ligand magnetic coupling was studied in the solid state by magnetometric (SQUID) measurements and by quantum chemical (DFT) calculations. The temperature dependence of the paramagnetic NMR shift was used for the evaluation of the magnetic coupling between the Ni centers and the pi-radical in solution. PMID- 26814472 TI - Abstracts : 11(th) European Congress of Trauma and Emergency Surgery May 15-18, 2010 Brussels, Belgium. PMID- 26814471 TI - Exosome-mediated communication in the ovarian follicle. AB - Cells are able to produce and release different types of vesicles, such as microvesicles and exosomes, in the extracellular microenvironment. According to the scientific community, both microvesicles and exosomes are able to take on and transfer different macromolecules from and to other cells, and in this way, they can influence the recipient cell function. Among the different macromolecule cargos, the most studied are microRNAs. MicroRNAs are a large family of non coding RNAs involved in the regulation of gene expression. They control every cellular process and their altered regulation is involved in human diseases. Their presence in mammalian follicular fluid has been recently demonstrated, and here, they are enclosed within microvesicles and exosomes or they can also be associated to protein complexes. The presence of microvesicles and exosomes carrying microRNAs in follicular fluid could represent an alternative mechanism of autocrine and paracrine communication inside the ovarian follicle. The outcomes from these studies could be important in basic reproductive research but could also be useful for clinical application. In fact, the characterization of extracellular vesicles in follicular fluid could improve reproductive disease diagnosis and provide biomarkers of oocyte quality in ART (Assisted Reproductive Treatment). PMID- 26814473 TI - [MRI methods for pulmonary ventilation and perfusion imaging]. AB - CLINICAL/METHODICAL ISSUE: Separate assessment of respiratory mechanics, gas exchange and pulmonary circulation is essential for the diagnosis and therapy of pulmonary diseases. Due to the global character of the information obtained clinical lung function tests are often not sufficiently specific in the differential diagnosis or have a limited sensitivity in the detection of early pathological changes. STANDARD RADIOLOGICAL METHODS: The standard procedures of pulmonary imaging are computed tomography (CT) for depiction of the morphology as well as perfusion/ventilation scintigraphy and single photon emission computed tomography (SPECT) for functional assessment. METHODICAL INNOVATIONS: Magnetic resonance imaging (MRI) with hyperpolarized gases, O2-enhanced MRI, MRI with fluorinated gases and Fourier decomposition MRI (FD-MRI) are available for assessment of pulmonary ventilation. For assessment of pulmonary perfusion dynamic contrast-enhanced MRI (DCE-MRI), arterial spin labeling (ASL) and FD-MRI can be used. PERFORMANCE: Imaging provides a more precise insight into the pathophysiology of pulmonary function on a regional level. The advantages of MRI are a lack of ionizing radiation, which allows a protective acquisition of dynamic data as well as the high number of available contrasts and therefore accessible lung function parameters. ACHIEVEMENTS: Sufficient clinical data exist only for certain applications of DCE-MRI. For the other techniques, only feasibility studies and case series of different sizes are available. The clinical applicability of hyperpolarized gases is limited for technical reasons. PRACTICAL RECOMMENDATIONS: The clinical application of the techniques described, except for DCE-MRI, should be restricted to scientific studies. PMID- 26814474 TI - Normative values for the L5 incidence in a subgroup of transitional anomalies extracted from 147 asymptomatic subjects. AB - PURPOSE: Pelvic incidence angle is not always measurable due to lumbosacral transitional vertebrae (LSV). The fifth lumbar vertebra (L5) is rarely abnormal. The purpose of this study was to quantify from full-body standing X-rays, the L5 incidence angle (L5I) in a normal asymptomatic population and to correlate it with standard spino-pelvic parameters taking the sacrum (S1) as a reference. METHODS: One hundred and forty seven asymptomatic volunteers were enrolled. The ethics committee approved the study protocol. Subjects underwent a low-dose full spine X-ray. 3D reconstructions were obtained and L5I was measured using the upper L5 endplate as the reference instead of the S1 endplate. A group of subjects with LSV was identified and subdivided in two subgroups. Standard spino pelvic parameters and normative values for the L5 parameters were obtained. Statistical correlations were calculated between the standard and L5 parameters as well as L5I with L1-L5 lordosis in both subgroups. RESULTS: Twenty two (14.96 %) subjects with LSV were found. Ten of these had an unidentifiable S1 endplate due to a sacralisation of L5. Mean values for the L5I, L5 tilt, L5 slope and L1 L5 lordosis were, respectively, 22.43, 4.65, 17.73, and 45.51 for normal subjects (N = 137) and 32.75, 6.63, 26.38, and 55.02 for sacralisation of L5 subjects (N = 10). Mathematical relationship found: L5I = 0.7641 * PI - 17.725 (R = 0.83) and L1-L5 = 0.67 * L5I + 30.7 (R = 0.64). CONCLUSION: This prospective study is first to provide normative spino-pelvic values at the L5 level in an asymptomatic population, particularly in case of (LSV) sacralisation of L5 (N = 10) where L5I and L1-L5 lordosis appears to be 10 degrees more important than in normal population. We propose L5I as a new spino-pelvic parameter to restore in case of L5-S1 disk disease. These normative values will help to control peri-operatively the adequate lordosis restoration, in the presence of LSV. PMID- 26814475 TI - Comparison of unilateral versus bilateral percutaneous kyphoplasty for the treatment of patients with osteoporosis vertebral compression fracture (OVCF): a systematic review and meta-analysis. AB - PURPOSE: To compare the short- and long-term clinical outcomes, operation times, restoration rate, dosage of polymethylmeth-acrylate (PMMA) injected, complications and X-rays exposure frequency between unilateral and bilateral kyphoplasty approaches for the treatment of OVCF. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Randomized or non-randomized controlled trials published up to April 2015 that compared the unilateral and bilateral PKP for the treatment of OVCF were acquired by a comprehensive search in the Cochrane Controlled Trial Register, PubMed, MEDLINE, EMBASE, Web of Science, OVID. Exclusion criteria were patients with neoplastic etiology (metastasis or myeloma), infection, neural compression syndrome, invasive and degenerative disease, traumatic fracture, re-operation, neurological deficits, significant scoliosis and spinal stenosis. The main end points included: operation times, the short- and long-term postoperative Visual Analogue Scale (VAS) scores, the short term postoperative Oswestry Disability Index (ODI), restoration rate, dosage of PMMA injected, cement leakage, X-ray exposure frequency and postoperative adjacent-level fractures. RESULTS: A total of 8 studies involving 428 patients were included in the meta-analysis. The mean operative time was shorter in the unilateral groups compared with the bilateral groups [P < 0.05, weighted mean difference (WMD) -19.74 (-30.56, -8.92)]. There was no significant difference in the short-term postoperative VAS scores [P > 0.05, WMD 0.03 (-0.34, 0.40)], the long-term postoperative VAS scores between them [P > 0.05, WMD 0.01 (-0.42, 0.45)] and the short-term postoperative ODI [P > 0.05, WMD -0.33 (-2.36, 1.69)] between the two groups. The unilateral approaches required significantly less dosage of PMMA than the bipedicular approaches did [P < 0.05, WMD -1.56 (-1.59, 1.16)]. The restoration rate in the bilateral groups was higher than the unilateral groups [P < 0.05, WMD -7.82 (-12.23, -3.41)]. There was no significant difference in the risk ratio of cement leakage [P > 0.05, RR 0.86 (0.36, 2.06)] and postoperative adjacent-level fractures [P > 0.05, RR 0.91 (0.25, 3.26)] between the two methods. The mean X-ray exposure frequency in the unilateral groups was greater than the bilateral groups [P < 0.05, WMD -5.69 (-10.67, 0.70)]. CONCLUSIONS: A definitive verdict could not be reached regarding which approach is better for the treatment of OVCF. Although unilateral PKP was associated with shorter operative time, less X- ray exposure frequency and dosage of PMMA than bilateral PKP. There was no apparent difference in the short- and long-term clinical outcomes and complications between them. However, bilateral PKP approaches were higher than unilateral PKP in term of the restoration rate. But on account of lack of some high-quality evidence, we hold that amounts of high-quality randomized controlled trials should be required and more complications should be analysed to resolve which surgical approach is better for the treatment of OVCF in the future. PMID- 26814476 TI - Dimensional changes of cervical and lumbar bony spinal canals in one generation in Western Switzerland: a computed tomography study. AB - PURPOSE: We aimed to study generational changes in the dimensions of cervical and lumbar bony spinal canals in Western Switzerland. METHODS: A total of 254 patients were retrospectively included, 144 of whom were born during 1940-1949 and 110 during 1970-1979. Cervical spine CTs were performed as part of the spinal clearance procedure following trauma (n = 135) or while investigating neurological symptoms (CT angiography, n = 119). Three independent observers digitally measured the cross-sectional area (CSA) at pedicle levels from C0 to C7 and the anteroposterior diameter (APD) at C3, C5, and C7. In addition, lumbar spine CSAs and APDs were measured on whole body trauma or abdominal CTs, which were also available for 134 patients. RESULTS: Mean CSAs at pedicle levels were numerically smaller in the younger patient group in both cervical and lumbar spine, with the difference reaching statistical significance at all lumbar levels (p <= 0.024) except L5. Cervical APDs showed no difference between groups. Subgroup analysis revealed that younger CT angiography patients had a significantly smaller CSA at C1 (p = 0.018) and a similar trend at C4 (p = 0.053). There was moderate positive correlation between cervical and lumbar CSAs, taking C4 and L3 as reference (r = 0.509, p < 0.01). CONCLUSIONS: Younger generation patients have smaller bony spinal canals also in the cervical spine even though this difference is less marked than at the lumbar level. There is, nevertheless, moderate positive correlation between these two anatomical regions. Perinatal factors that adversely influence spinal growth, such as increased maternal age and smoking, could explain these generational changes, given that body height has increased during the same time period. The lesser difference observed in the cervical spine could be due to later closure of the neurocentral synchondrosis at this level. PMID- 26814477 TI - Double-level degenerative spondylolisthesis: what is different in the sagittal plane? AB - PURPOSE: Degenerative spondylolisthesis (DS) is a common disease. The importance of sagittal malalignment in the DS population has been widely described. However, there is no study reporting sagittal alignment analysis in double-level DS. This study aims to analyze patients with double-level DS and compare them with single level DS patients in terms of demographic and radiographic data. METHODS: Retrospective multicenter (n = 13) study. Adult patients with one (uni_DS) or two level DS (multi_DS) were included. Sagittal radiographic parameters were measured by an experienced observer: pelvic, spinal and global parameters with C7 sagittal tilt (C7 tilt, angle between the center of C7 vertebral body and the middle of the sacral endplate with the vertical reference line). After a descriptive analysis, radiographic and demographic data were compared between single and multi_DS. RESULTS: 78 patients were included in multi_DS group and 576 in uni_DS group. Multi_DS were older than uni_DS (70.2 +/- 9.4 vs 66.9 +/- 10.6 years, p = 0.009). C7tilt was greater in multi_DS (6.2 degrees +/- 5.3 vs. 4.8 degrees +/- 3.8, p = 0.003). Multi_DS had a greater pelvic incidence (62.4 degrees +/- 11.3 vs. 58.3 degrees +/- 11.1, p = 0.002). Pelvic tilt was larger in multi-DS (26.0 degrees +/- 7.5 vs. 22.6 degrees +/- 8.1, p = 0.001). L4S1 lordosis represented 40.4 % of the LLmax in multi_DS and 45.8 % in uni_DS group (p = 0.013). CONCLUSIONS: Multi_DS have different sagittal alignment than single DS with greater PI. In multi_DS, malalignment is more important with larger anterior tilt, loss of lumbosacral lordosis and more compensatory mechanisms such as pelvic retroversion. These findings highlight the need for an adapted surgical correction in these older patients with greater sagittal malalignment. PMID- 26814478 TI - The Severity of Visceral Leishmaniasis Correlates with Elevated Levels of Serum IL-6, IL-27 and sCD14. AB - BACKGROUND: Visceral leishmaniasis (VL) is a severe disease caused by infection with protozoa of the genus Leishmania. Classic VL is characterized by a systemic infection of phagocytic cells and an intense activation of the inflammatory response. It is unclear why 90% of infected individuals do not develop the disease while a minority develop the classical form. Furthermore, among those that develop disease, a small group progresses to more severe form that is unresponsive to treatment. The presence of inflammatory mediators in serum could theoretically help to control the infection. However, there is also a release of anti-inflammatory mediators that could interfere with the control of parasite multiplication. In this study, we took advantage of the spectrum of outcomes to test the hypothesis that the immune profile of individuals infected with Leishmania (L.) infantum is associated with the development and severity of disease. METHODOLOGY/PRINCIPAL FINDINGS: Sera from patients with confirmed diagnosis of VL were evaluated for the presence of numerous molecules, and levels compared with healthy control and asymptomatic infected individuals. CONCLUSIONS/PRINCIPAL FINDINGS: Although differences were not observed in LPS levels, higher levels of sCD14 were detected in VL patients. Our data suggest that L. infantum may activate the inflammatory response via CD14, stimulating a generalized inflammatory response with production of several cytokines and soluble molecules, including IFN-gamma, IL-27, IL-10, IL-6 and sCD14. These molecules were strongly associated with hepatosplenomegaly, neutropenia and thrombocytopenia. We also observed that IL-6 levels greater than 200 pg/ml were strongly associated with death. Together our data reinforce the close relationship of IFN-gamma, IL-10, IL-6, TNF-alpha and IL-27 in the immune dynamics of VL and suggest the direct participation of sCD14 in the activation of the immune response against L. infantum. PMID- 26814479 TI - Reduced Personal Space in Individuals with Autism Spectrum Disorder. AB - Maintaining an appropriate distance from others is important for establishing effective communication and good interpersonal relations. Autism spectrum disorder (ASD) is a developmental disorder associated with social difficulties, and it is thus worth examining whether individuals with ASD maintain typical or atypical degrees of social distance. Any atypicality of social distancing may impact daily social interactions. We measured the preferred distances when individuals with ASD and typically developing (TD) individuals approached other people (a male experimenter) and objects (a coat rack with clothes) or when other people approached them. Individuals with ASD showed reduced interpersonal distances compared to TD individuals. The same tendency was found when participants judged their preferred distance from objects. In addition, when being approached by other people, both individuals with ASD and TD individuals maintained larger interpersonal distances when there was eye contact, compared to no eye contact. These results suggest that individuals with ASD have a relatively small personal space, and that this atypicality exists not only for persons but also for objects. PMID- 26814480 TI - Health-related quality of life questionnaire for polycystic ovary syndrome (PCOSQ 50): development and psychometric properties. AB - PURPOSE: The determinants of the health-related quality of life of women with polycystic ovary syndrome are not fully understood. The aim of this study was to develop a comprehensive instrument to assess the health-related quality of life of Iranian women with PCOS and to assess its psychometric properties. METHODS: We used a mixed-method, sequential, exploratory design including both qualitative [in-depth interview to define the components of health-related quality of life questionnaire (PCOSQ)] and quantitative approaches (to assess the psychometric properties of PCOSQ). RESULTS: A preliminary questionnaire was developed including 147 items which emerged from the qualitative phase of the study. Considering the optimum cutoff points for content validity ratio (CVR), content validity index (CVI), and impact score, items of the preliminary questionnaire were reduced from 147 to 88 items. Finally, by excluding highly correlated items using the exploratory factor analysis, a 50-item questionnaire was obtained. The Kaiser criteria (eigenvalues >1) and Scree plot tests demonstrated that six factors were optimum with an estimated 47.3 % of variance. Assessment of the psychometric properties of the questionnaire demonstrated a mean CVI = 0.92, CVR = 0.91, Cronbach's alpha for whole questionnaire = 0.88 (0.61-0.88 for subscales), Spearman's correlation coefficients of test-retest = 0.75, and the intra-class correlation coefficient for the PCOS questionnaire subscales ranging from 0.57 to 0.88. Eventually the final questionnaire included 50 items in six domains, 'psychosocial and emotional,' 'fertility,' 'sexual function,' 'obesity and menstrual disorders,' 'hirsutism,' and 'coping' and rated on a 5-point Likert scale. CONCLUSION: The PCOSQ-50 is a valid and reliable instrument for the assessment of quality of life of women with PCOS, capable of assessing some obscure aspects overlooked by previous HRQL questionnaires. PMID- 26814482 TI - Focus on Pancreatic and Duodenal Injuries. PMID- 26814483 TI - Nonoperative Management of Pancreato-Duodenal Injuries. AB - Following injuries to the pancreas and duodenum (PDI) patients often present in extremis and undergo immediate laparotomy for hemodynamic instability and peritoneal signs. Nonoperative management (NOM) may be offered in selected patients with lowgrade injuries. Precise mapping of the injury, most commonly by computed tomography, is a prerequisite for NOM because clinical symptomatology can be variable and misleading. Additionally, delaying the treatment of PDI that should be corrected surgically may lead to significant complications. Therefore, NOM of PDI presents unique challenges, and the decision-making is not as straightforward as it is with NOM of other solid abdominal organs. Essentially, only duodenal hematomas without fullthickness wall perforation (Grade I and selected II) and pancreatic trauma without major duct involvement (Grade I and selected II) could be offered NOM. In these cases, the reported success rates vary from 74 to 95%. There are also a few severe pancreatic injuries that can be managed by stents with adequate reconstitution of the major pancreatic duct integrity and resolution of symptoms and without the need for operative management. Intensive monitoring and follow-up by clinical examination and repeat CT imaging is essential in these patients, as the risk of complications, and particularly a pseudocyst is high. PMID- 26814481 TI - Capsule Design for Blue Light Therapy against Helicobacter pylori. AB - A photo-medical capsule that emits blue light for Helicobacter pylori treatment was described in this paper. The system consists of modules for pH sensing and measuring, light-emitting diode driver circuit, radio communication and microcontroller, and power management. The system can differentiate locations by monitoring the pH values of the gastrointestinal tract, and turn on and off the blue light according to the preset range of pH values. Our experimental tests show that the capsule can operate in the effective light therapy mode for more than 32 minutes and the wireless communication module can reliably transmit the measured pH value to a receiver located outside the body. PMID- 26814484 TI - Treatment of Pancreatic Fistulas. AB - Pancreatic fistula is usually a complication of acute and chronic pancreatitis but can also occur postoperatively or after abdominal trauma. Conservative treatment of pancreatic fistula is time-consuming and often fails. Endoscopic treatment has become the preferred first-line treatment in many centres. Surgery is necessary in few cases when endoscopy fails or is not technically possible. PMID- 26814485 TI - Duodenal Injuries: A Review. AB - Duodenal injuries are uncommon injuries but are associated with significant morbidity and mortality from a delayed diagnosis in the case of blunt trauma and associated major vascular injuries in penetrating trauma. A simplistic approach with primary repair or resection and anastomosis is ideal for the vast majority. Complex procedures such as pyloric exclusion with or without gastrojejunostomy may be indicated for delayed treatment or severe, high-grade combined pancreato duodenal injuries. A high index of suspicion and a judicious treatment plan based on a careful consideration of all the available options are crucial for optimal outcome. PMID- 26814486 TI - Pressure Ulcers and Prolonged Hospital Stay in Hip Fracture Patients Affected by Time-to-Surgery. AB - BACKGROUND: Hip fractures are associated with high morbidity. Pressure ulcer formation after hip surgery is often related to delayed patient mobilization. The objectives of this study were to determine whether time-to-surgery affects development of pressure ulcers postoperatively and, thus, length of hospital stay. PATIENTS AND METHODS: We performed a retrospective analysis of consecutive hip fracture patients, aged 60 years and above, who underwent surgery between 1995 and 2001. The primary outcome was in-hospital development of pressure ulcers. The secondary outcome measure was the overall length of hospital stay. Analyses were adjusted for relevant confounders. RESULTS: Of the 722 patients enrolled, 488 patients (68%) received surgery at 12 h after admission. Approximately 30% (n = 214) developed pressure ulcers during admission, whilst 19% of patients operated within 12 h of admission developed pressure ulcers. Time to-surgery was an independent predictor of both development of pressure ulcers (OR = 1.7, 95% confidence interval [CI] = 1.2-2.6; p = 0.008) and length of hospital stay (11.3 vs 13.3 days in the early and the late surgery group, respectively, p = 0.050). Furthermore, development of pressure ulcers was associated with prolonged postoperative hospital stay (19.5 vs 11.1 days for patients with and without pressure ulcers, respectively, p = 0.001) INTERPRETATION: : In hip fracture patients, time-to-surgery was an independent predictor of both postoperative pressure ulcer development and prolonged hospital stay. These data suggest that the implementation of an early surgery protocol following admission for hip fractures may reduce both the postoperative complications and overall hospital stay. PMID- 26814487 TI - The Finnish Forward Surgical Team Experience During EUFOR Operation RD Congo in 2006. AB - The army Forward Surgical Team (FST) is a mobile surgical asset designed to provide life- and limbsaving combat surgery in remote and austere terrains. Operation EUFOR RDC in Democratic Republic of the Congo (DRC) in 2006 was the first one planned and conducted solely by the European Union Forces (EUFOR). The first two European FSTs reported in the present article were established by the Finnish Defence Forces.The Finnish FSTs were deployed for 4 months in Kinshasa. Three different deployment scenarios were trained; the equipments loaded on two trucks and carried by two C-130 aircrafts, the equipments loaded on two aircraft pallets (no trucks) and carried by one C-130 aircraft, and the equipments loaded on and carried by two CH-53 helicopters. The FSTs were deployed in three tactical and four reconnaissance operations. Due to the peacekeeping nature of the Operation, the surgical medical workload was light. The total number of patients treated by FSTs was 12,5 of them being due to trauma and 7 to medical condition. All trauma cases were of noncombat origin, and only one of them was severe.The European FST concept should be developed for future missions regarding the experiences gained during the reported deployment, the main goals being the mobility and the lightness of the unit. This kind of special trauma surgical asset, designed for remote theatres, will possibly be useful also in other emergency operations taking place in non-conventional circumstances; a concept of FST could easily be deployed in short notice to various accidental and natural disasters. PMID- 26814488 TI - Cost Analysis of Vertical Deceleration Injury in the Acute Setting. AB - INTRODUCTION: Vertical deceleration injury is a known but not well understood form of blunt injury in both the urban and rural environment. The purpose of this study was to investigate the financial cost of treatment for this specific mechanism of injury in the acute care setting, and to continue to expand a fall prevention program from our unit. METHOD: This is a prospective review of vertical deceleration injuries admitted over a 2-year period to a Level I trauma center. Patients were followed until discharge to either home or rehabilitation facilities. RESULTS: Ninety-nine patients who sustained a vertical deceleration injury from a height of >= 6 ft were identified from our Trauma Registry database. The length of hospital stay, including rehabilitation, ranged from 1 to 78 days (mean, 13.1 days). The mean injury severity score (ISS) was 16.4 (range, 4-75). The average height of fall was 19.5 ft (range, 6-110 ft) with a mean impact velocity of 23 mph (range, 13-58). The cost of hospitalization was significantly correlated to the ISS score (correlation = 0.558, p < 0.001); and as expected, higher ISS scores yielded higher costs (chi(2) = 34.7, p < 0.001). We found that the best predictor variable for the cost of treatment for vertical deceleration injury is the ISS score with a regression equation of: Cost = $19,578 + ($6,609 * ISS). The average cost per fall incident was $91,435 (range $5,006-$948,957) for vertical deceleration injuries. CONCLUSION: The cost of treatment of vertical deceleration injuries is very high. Hospital stays are prolonged and rehabilitation needs frequent. Overall, ISS is the best predictor of cost of treatment and length of hospital stay. PMID- 26814489 TI - Changing the Management from Olecranon Screw Traction to Percutaneous Wiring for Displaced Supracondylar Fractures of the Humerus in Children. A Justified Decision? AB - BACKGROUND AND PURPOSE: In this institution, the management of displaced (Gartland III) supracondylar fractures in children was changed from overhead olecranon screw traction to manipulation and percutaneous wiring in 1996. The purpose of this study was to compare the two methods of treatment and observe whether the decision to change management was justified. METHODS: A retrospective study of two cohorts; 151 patients between 1986 and 1996 treated with olecranon screw traction and 92 patients between 1996 and 2002 treated with percutaneous wiring. Both sets of patients were followed up clinically and radiologically until the child could demonstrate a satisfactory range of movement and the fracture had united. RESULTS: There were no differences in the clinical outcomes between the two groups. The main difference between the groups was in length of stay, which was a median of 1 day in the wired group and 14 days in the traction group. CONCLUSION: Outcomes achieved from percutaneous wiring of displaced supracondylar fractures are similar to those from olecranon screw traction. The advantage of percutaneous wiring to both patient and provider is the reduced hospital stay. The decision to change management therefore appears to be justified. However, percutaneous wiring is generally a technically more demanding procedure and olecranon screw traction should remain a possible treatment option for the management of this injury. PMID- 26814490 TI - Complications after Intramedullary Stabilization of Proximal Femur Fractures: a Retrospective Analysis of 178 Patients. AB - Secondary dislocation, non-union, re-fracture and implant failure are generally known complications after intramedullary fixation of proximal femur fractures with the PFN((r)) (Synthes GmbH, Solothurn, Switzerland). The goal of our study was to assess the impact of patient- and treatment-specific risk factors on these complications. Complex fracture type and poor bone quality were defined as patient-specific risk factors. Inadequate fracture reduction and implant position were defined as treatment-specific risk factors. One hundred and seventy-eight cases were retrospectively analyzed. All patients had at least one clinical and radiological follow-up examination 3-6 months after the operation. Fifty percent of the patients were available for one more follow-up at least 1 year after the operation. All patients without patient-specific risk factors had a good outcome, irrespective of whether treatmentspecific risk factors were present or absent. In 153 of the 178 cases, patients had a complex type of fracture and/or poor bone quality. Of these patients, 27 (15.2%) had a poor result. Twenty-four of these patients needed re-operation within 6 months. Complication rate in these patients highly depended on treatment-specific risk factors. We conclude that the PFN is a secure implant for the stabilization of simple cases. Stabilization of complex proximal femoral fractures with the PFN, however, has a relevant complication rate and should therefore be considered a challenge. PMID- 26814491 TI - Guidelines for Quality Management of Apallic Syndrome / Vegetative State. AB - INTRODUCTION: Epidemiology in Europe shows constantly increasing figures for the apallic syndrome (AS)/vegetative state (VS) as a consequence of advanced rescue, emergency services, intensive care treatment after acute brain damage and high standard activating home nursing for completely dependent end-stage cases secondary to progressive neurological disease. Management of patients in irreversible permanent AS/VS has been the subject of sustained scientific and moral-legal debate over the past decade. METHODS: A task force on guidelines for quality management of AS/VS was set up under the auspices of the Scientific Panel Neurotraumatology of the European Federation of Neurological Societies to address key issues relating to AS/VS prevalence and quality management. Collection and analysis of scientific data on class II (III) evidence from the literature and recommendations based on the best practice as resulting from the task force members' expertise are in accordance with EFNS Guidance regulations. FINDINGS: The overall incidence of new AS/VS full stage cases all etiology is 0.5-2/100.000 population per year. About one third are traumatic and two thirds non traumatic cases. Increasing figures for hypoxic brain damage and progressive neurological disease have been noticed. The main conceptual criticism is based on the assessment and diagnosis of all different AS/VS stages based solely on behavioural findings without knowing the exact or uniform pathogenesis or neuropathological findings and the uncertainty of clinical assessment due to varying inclusion criteria. No special diagnostics, no specific medical management can be recommended for class II or III AS treatment and rehabilitation. This is why sine qua non diagnostics of the clinical features and appropriate treatment of AS/VS patients of "AS full, remission, defect and end stages" require further professional training and expertise for doctors and rehabilitation personnel. INTERPRETATION: Management of AS aims at the social reintegration of patients or has to guarantee humanistic active nursing if treatment fails. Outcome depends on the cause and duration of AS/VS as well as patient's age. There is no single AS/VS specific laboratory investigation, no specific regimen or stimulating intervention to be recommended for improving higher cerebral functioning. Quality management requires at least 3 years of advanced training and permanent education to gain approval of qualification for AS/VS treatment and expertise. Sine qua non areas covering AS/VS institutions for early and long-term rehabilitation are required on a population base (prevalence of 2/100.000/year) to quicken functional restoration and to prevent or treat complications. Caring homes are needed for respectful humane nursing including basal sensor-motor stimulating techniques. Passive euthanasia is considered an act of mercy by physicians in terms of withholding treatment; however, ethical and legal issues with regard to withdrawal of nutrition and hydration and end of life discussions raise deep concerns. The aim of the guideline is to provide management guidance (on the best medical evidence class II and III or task force expertise) for neurologists, neurosurgeons, other physicians working with AS/VS patients, neurorehabilitation personnel, patients, next-of-kin, and health authorities. PMID- 26814492 TI - Proximal Radio-Ulnar Synostosis at the Pin-Track Site after External Fixation of the Forearm. AB - Posttraumatic synostosis of the forearm bones is a rare but serious complication following fixation or even conservative treatment of adult forearm fractures. This is the second report in the English literature of such a complication at the pin-track site following external fixation of proximal forearm fractures. A 36 year-old male patient sustained an open fracture of his proximal right forearm after a road traffic accident. It was managed by external fixation of the ulna and plate fixation of the radius. At follow-up, a type 3 radio-ulnar synostosis at the pin-track site became evident, which was treated after 20 months with surgical resection of the bony bridge to regain the rotatory motion of his forearm. PMID- 26814493 TI - Proximal Radio-Ulnar Synostosis at the Pin-Track Site after External Fixation of the Forearm. AB - Posttraumatic synostosis of the forearm bones is a rare but serious complication following fixation or even conservative treatment of adult forearm fractures. This is the second report in the English literature of such a complication at the pin-track site following external fixation of proximal forearm fractures. A 36- year-old male patient sustained an open fracture of his proximal right forearm after a road traffic accident. It was managed by external fixation of the ulna and plate fixation of the radius. At follow-up, a type 3 radio-ulnar synostosis at the pin-track site became evident, which was treated after 20 months with surgical resection of the bony bridge to regain the rotatory motion of his forearm. PMID- 26814494 TI - Blast-Induced Colon Perforation Secondary to Civilian Gunshot Wound. AB - Gunshot injuries sustained from rifle bullets in general are associated with more severe tissue destruction than similar injuries due to handgun bullets. This includes damage not directly attributable to the missile itself, in other words, that due to cavitation. We describe herein a colonic injury following a 0.223 caliber rifle bullet injury presumably due solely to blast effect. PMID- 26814495 TI - Gluteal Soft Tissue Necrosis After Transcatheter Angiographic Embolization for Pelvic Fracture: a Report of Two Cases. AB - In this paper, two cases of the gluteal soft tissue necrosis after pelvic fractures will be discussed. In the case of a 29-year-old man, a localized area of skin necrosis on the buttock appeared after transcatheter arterial embolization (TAE) of the right internal iliac artery (IIA). In the second case, a 52-year-old man, who was treated using TAE of the bilateral IIA's, developed an extensive area of necrosis in the gluteus maximus muscle with subsequent severe infection. In both cases, complete excision of the necrotic tissue and reconstructive flap surgery were imperative. Gluteal soft tissue necrosis is clinically important as one of the serious complications of TAE. PMID- 26814496 TI - Traumatic Hemipelvectomy: A Case Report and a Review of the Literature. AB - Traumatic hemipelvectomy is a life threatening, devastating pelvic injury with very low survival rates. Excessive loss of blood, related systemic problems and additional injuries about the gastrointestinal and genitourinary systems increase mortality of this severe sort of injury. A young, male farmer injured violently by an agricultural heavy machine; a survivor of traumatic hemipelvectomy is described in this case report. PMID- 26814497 TI - Hemiarthroplasty for Humeral Head Fractures. AB - OBJECTIVE: Replacement of the fractured humeral head with a modular prosthesis. The procedure aims at an adequate reconstruction of shape and function of the shoulder. INDICATIONS: Displaced three- and four-part fractures of the proximal humerus that cannot be reduced and internally fixed. CONTRAINDICATIONS: Fracture can be reduced and adequately internally fixated. Noncompliant patient. SURGICAL TECHNIQUE: In beach-chair position, the fractured humeral head is removed via a deltopectoral approach. The Aequalis modular fracture prosthesis can be positioned by two methods: (i) a fracture jig optimizing height and retroversion of the prosthesis, (ii) under additional intraoperative fluoroscopy. Healing of the tuberosities can be promoted by cancellous grafts taken from the fractured head. These are fixed by four heavy sutures running horizontally and two sutures running vertically. RESULTS: 13 out of 22 patients treated by primary hemiarthroplasty (within 10 days after the fracture) and 34 out of 50 patients treated by secondary arthroplasty could be assessed after a mean follow-up of 40 (15-70) and 44 (8-98) months, respectively. The absolute Constant score amounted to 45 and 50 points, respectively, and the relative score to 56% in both groups. The majority of patients was free of pain or suffered less pain than before the operation (secondary arthroplasty; p < 0.001). In contrast to these, only satisfactory, objective results, self-assessment was good or better than before (secondary prostheses; p < 0.001). In both groups, prognostic factors were the size and position of the tuberosities (p < 0.001). PMID- 26814498 TI - 26th Meeting of the Pediatric Section of the German Society of Trauma Surgeons (DGU) June 21-23, 2007 Graz, Austria. PMID- 26814499 TI - Good and complete responding locally advanced rectal tumors after chemoradiotherapy: where are the residual positive nodes located on restaging MRI? AB - PURPOSE: Aim of this study was to evaluate the distribution of persistent mesorectal lymph node metastases on restaging MRI in patients with a good or complete response of their primary tumor (ypT0-2) after CRT for locally advanced rectal cancer. METHODS: Two hundred and twenty eight locally advanced rectal cancer patients underwent CRT, which resulted in a good response (downstaging to yT0-2) in 144 patients. Forty-nine patients were excluded (no surgery/insufficient follow-up or lacking lesion-by-lesion histology results). This resulted in a final study group of 95 yT0-2 patients. For the patients with a yN(+)-status, a detailed lesion-by-lesion comparison between restaging MRI and histology was performed to evaluate the characteristics and distribution of the individual N(+)-nodes. RESULTS: 7/95 patients (7%) had a yT0-2N(+) status (11/880 (1%) N(+) nodes): no N(+) were found below the tumor level, 55% of the N(+) nodes were located at the level of the tumor, and 45% proximal to the tumor (at a median distance of 1.4 cm above the tumor level). In axial plane, 82% of the nodes were located at the ipsilateral circumference of the tumor, at a median distance of 0.9 cm from the tumor/rectal wall. CONCLUSIONS: The incidence of persistent metastatic mesorectal nodes after CRT in patients with a good tumor response after CRT is very low. No N(+) nodes are found below the tumor level. All N(+) nodes are located at the level of or proximal to the primary tumor, of which the majority very close to the tumor/lumen. PMID- 26814500 TI - Risk factors for radiation exposure in newly diagnosed IBD patients. AB - PURPOSE: Patients with inflammatory bowel disease (IBD) may be exposed to high doses of diagnostic radiation. The purpose of this study is to identify subsets of this population at risk for significant radiation exposure. METHODS: This HIPAA compliant, IRB approved study consists of 336 patients (237 adult and 99 pediatric) within the Ocean State Crohn's & Colitis Area Registry (OSCCAR). All were newly diagnosed with IBD and prospectively enrolled between 1/2008 and 12/2012. Comprehensive chart review was performed. RESULTS: 207 (61.6%) patients were diagnosed with Crohn's disease (CD), 120 (35.7%) with ulcerative colitis (UC), and 9 (2.7%) with inflammatory bowel disease, type unspecified (IBDU). 192 (57.1%) patients were exposed to GI-specific radiation. Average GI-specific radiation dose for adult IBD patients was 14.1 mSV and was significantly greater among adult CD than adult UC patients (p = 0.01). Pediatric patients underwent fewer CT scans (p < 0.0001). Risk factors for increased radiation exposure include: GI surgery (p = 0.003), biologic therapy (p = 0.01), pain-predominant symptoms (as compared to diarrhea-predominant symptoms; p < 0.05), and isolated ileal disease (p = 0.02). Patients with stricturing or penetrating disease received higher radiation doses than patients with non-stricturing, non penetrating disease (p < 0.0001). CONCLUSIONS: A variety of risk factors are associated with increased exposure to ionizing radiation after diagnosis of IBD. Knowledge of these risk factors can help physicians prospectively identify patients at risk for elevated radiation exposure and consider low-dose or radiation-free imaging. PMID- 26814501 TI - The expanding landscape of diffusion-weighted MRI in prostate cancer. AB - The added value of diffusion-weighted magnetic resonance imaging (DW-MRI) for the detection, localization, and staging of primary prostate cancer has been extensively reported in original studies and meta-analyses. More recently, DW-MRI and related techniques have been used to noninvasively assess prostate cancer aggressiveness and estimate its biological behavior. The present article aims to summarize the potential applications of DW-MRI for noninvasive optimization of pretherapeutic risk assessment, patient management decisions, and evaluation of treatment response. PMID- 26814502 TI - Computed tomography features of gastrointestinal linitis plastica: spectrum of findings in early and delayed phase imaging. AB - PURPOSE: To analyze the features of gastrointestinal linitis plastica obtained by computed tomography (CT). MATERIALS AND METHODS: We conducted a single-center, retrospective analysis of 45 cases of gastrointestinal tract linitis plastica collected over a 10-year period. "Linitis plastica" was defined based on histological characteristics. Primary and secondary linitis plastica were included. Two readers independently assessed the radiological findings (i.e., number of lesions, mass, wall thickening, and enhancement). RESULTS: The patient cohort comprised 23 men and 22 women with an average age of 63.2 years. The main presenting signs and symptoms were impaired general health and ascites (22/45 patients, 48.8%). The stomach was the affected organ in 68.3% of the cases, while the rectum was affected in 11.7% of the cases. Primary linitis was found in 73.3% of the cases, and solitary lesions were found in 77.8% of the cases. The most common CT finding was wall thickening (91.7%) with a complete disappearance of folds and enhancement of the entire wall at 2 min. Four lesions (6.6%) were described as masses, and only one (1.7%) was described as a wall atrophy. CONCLUSION: Linitis plastica can affect the entire digestive system. Its potentially secondary nature necessitates a systematic search for a primary tumor. An appropriate CT protocol is required to detect the specific radiological features of this fibrous cancer. CT can help confirm the diagnosis of linitis plastica, rule out differential diagnoses, and indicate the need for deep biopsies where possible. PMID- 26814503 TI - A Microarray-Based Analysis Reveals that a Short Photoperiod Promotes Hair Growth in the Arbas Cashmere Goat. AB - Many animals exhibit different behaviors in different seasons. The photoperiod can have effects on migration, breeding, fur growth, and other processes. The cyclic growth of the fur and feathers of some species of mammals and birds, respectively, is stimulated by the photoperiod as a result of hormone-dependent regulation of the nervous system. To further examine this phenomenon, we evaluated the Arbas Cashmere goat (Capra hircus), a species that is often used in this type of research. The goats were exposed to an experimentally controlled short photoperiod to study the regulation of cyclic cashmere growth. Exposure to a short photoperiod extended the anagen phase of the Cashmere goat hair follicle to increase cashmere production. Assessments of tissue sections indicated that the short photoperiod significantly induced cashmere growth. This conclusion was supported by a comparison of the differences in gene expression between the short photoperiod and natural conditions using gene chip technology. Using the gene chip data, we identified genes that showed altered expression under the short photoperiod compared to natural conditions, and these genes were found to be involved in the biological processes of hair follicle growth, structural composition of the hair follicle, and the morphogenesis of the surrounding skin appendages. Knowledge about differences in the expression of these genes as well as their functions and periodic regulation patterns increases our understanding of Cashmere goat hair follicle growth. This study also provides preliminary data that may be useful for the development of an artificial method to improve cashmere production by controlling the light cycle, which has practical significance for livestock breeding. PMID- 26814505 TI - Acute compartment syndrome. PMID- 26814504 TI - Antagonistic Effect of a Salivary Proline-Rich Peptide on the Cytosolic Ca2+ Mobilization Induced by Progesterone in Oral Squamous Cancer Cells. AB - A salivary proline-rich peptide of 1932 Da showed a dose-dependent antagonistic effect on the cytosolic Ca2+ mobilization induced by progesterone in a tongue squamous carcinoma cell line. Structure-activity studies showed that the activity of the peptide resides in the C-terminal region characterized by a proline stretch flanked by basic residues. Furthermore, lack of activity of the retro inverso peptide analogue suggested the involvement of stereospecific recognition. Mass spectrometry-based shotgun analysis, combined with Western blotting tests and biochemical data obtained with the Progesterone Receptor Membrane Component 1 (PGRMC1) inhibitor AG205, showed strong evidence that p1932 performs its modulatory action through an interaction with the progesterone receptor PGRMC1, which is predominantly expressed in this cell line and, clearly, plays a role in progesterone induced Ca2+ response. Thus, our results point to p1932 as a modulator of the transduction signal pathway mediated by this protein and, given a well-established involvement of PGRMC1 in tumorigenesis, highlight a possible therapeutic potential of p1932 for the treatment of oral cancer. PMID- 26814506 TI - The diagnosis of acute compartment syndrome: a review. AB - Delay in the diagnosis of acute compartment syndrome (ACS) has serious and sometimes catastrophic consequences for the outcome of injury, and has been recognised as one of the primary causes of a poor outcome. This article reviews the evidence for the use of clinical findings and intra-compartmental pressure (ICP) monitoring in making a prompt diagnosis of ACS. Clinical findings have poor sensitivities (13-64 %) compared to ICP monitoring (94 %) using a differential pressure threshold of less than 30 mmHg for more than 2 h. The specificities of clinical findings range from 63 to 98 % compared to a value of 98 % for ICP monitoring. Patients at risk of ACS or at risk of a delayed diagnosis are defined, and it is recommended that these patients undergo ICP monitoring. It is recommended that decompression is carried out primarily on the basis of the differential pressure being less than 30 mmHg for more than 2 h as this results in a reduced time to definitive treatment when compared to waiting for the development of clinical symptoms and signs. PMID- 26814507 TI - Mechanism of injury and treatment of trauma-associated acute compartment syndrome of the foot. AB - Acute compartment syndrome (ACS) of the foot represents a rare complication following trauma of the lower extremity. Early diagnosis and treatment are necessary to prevent poor outcome. The study was conducted to describe etiology and treatment of foot ACS. In the current study, patients diagnosed with and treated for ACS between 1st December 2000 and 30th September 2007 were included. Mechanism of injury, additional injuries and treatment was analyzed. We included 31 patients (21 males) with a mean age of 33.8 +/- 16.9 years. Most injuries were caused by a motor vehicle accident, while nearly 20 % occurred after a low-energy mechanism. Multiple injuries with a mean ISS of 19.5 +/- 11.0 were present in 14 patients. Superficial infections occurred in 6 feet, while a deep infection only developed in one patient. Acute compartment syndrome of the foot has a low incidence. A thorough clinical examination in patients on risk is required to provide timely diagnosis and adequate surgical decompression. PMID- 26814508 TI - Contrast enhanced ultrasound (CEUS) reliably detects critical perfusion changes in compartmental muscle: a model in healthy volunteers. AB - PURPOSE: The purpose of this study was to assess the utility of contrast enhanced ultrasound (CEUS) in the differentiation between physiological and simulated pathophysiological lower limb muscle perfusion pressures in healthy volunteers. METHODS: The lower limb muscle perfusion pressures in eight healthy volunteers were assessed in the supine position (as a control) and then subsequently in an elevated position with a thigh tourniquet applied to induce venous stasis. An intravenous bolus injection of 2.5 ml contrast agent was given to create a perfusion signal, which was measured with a multiple-frequency probe. Semiquantitative analysis was performed using specific software to create a perfusion curve which allowed measurement of six parameters: the time to arrival (TTA) starting from bolus application (s); peak of signal intensity (%); time to peak (TTP) maximum (seconds); regional blood volume (RBV), regional blood flow (RBF), and mean transit time (MTT) in seconds. Statistical analysis was performed using the Mann-Whitney U test as a non-parametric test (IBM SPSS statistics, version 21, USA). RESULTS: The group of simulated hypoperfusion showed significant higher values for TTA (39.8 +/- 5.1 s) (p = 0.028), TTP (43.8 +/- 13.6 s) (p = 0.003), RBV (8,424 +/- 5,405) (p = 0.028), and MTT (262 +/- 90.6 s) (p = 0.005). In contrast, the parameter of regional blood flow (32.1 +/- 10.9) was significantly lower (p = 0.038). The peak signal intensity (25.8 +/- 8.2 %) was lower, but this was not significant (p = 0.083). CONCLUSIONS: CEUS provides a reliable non-invasive imaging modality for the assessment of lower limb muscle perfusion pressures. This may be of clinical use in the assessment of a developing compartment syndrome. Further clinical studies are required to further define its accuracy and reproducibility. PMID- 26814509 TI - Autotransfusion in emergent operative trauma resuscitation. AB - PURPOSE: Autotransfusion of red cells is common in many surgical specialties. However, this technique is not uniformly used in abdominal trauma. The purpose of this paper is to study the outcomes of patients who were autotransfused during emergency trauma operations in which they sustained full-thickness hollow viscus injury (HVI). METHODS: A total of 179 patients in period 1999-2008 with penetrating and blunt abdominal trauma requiring intraoperative blood transfusion were evaluated. Recipients of autotransfusion and banked blood (autotransfused group) were compared with recipients of banked blood products only (control group). The t-test, Chi-squared, and Fisher's exact test were used to evaluate the data. Multivariate regression analysis evaluated the primary outcomes, survival and bloodstream infection (BSI). RESULTS: Of the 179 patients, 108 controls and 71 autotransfused patients were evaluated. The results showed no statistically significant difference between the control and autotransfusion groups regarding age, injury pattern/severity [Injury Severity Score (ISS)], length of stay, postoperative international normalized ratio (INR), and volume of banked blood products. Both groups were also proportional with colon injury. The estimated operative blood loss (EBL) was 2,472 +/- 3,261 for controls and 4,056 +/- 3,825 for the autotransfused group (p = 0.0001). The total volume of blood transfused was 2,792 and 5,513 for controls and patients in the autotransfusion group, respectively (p = 0.002). Ninety controls (84 %) and 53 autotransfused patients (76 %) survived to discharge (p = 0.21). Twenty controls (49 %) and 17 autotransfused patients (45 %) developed BSI (p = 0.72). Logistic regression analysis revealed that an ISS >25, systolic blood pressure <90, and EBL >2 L predicted mortality. There was also a trend towards decreased survival with age >50 years. CONCLUSION: We found no evidence that emergent autotransfusion worsens clinical outcomes in the setting of concomitant HVI. PMID- 26814510 TI - Risk factors for liver abscess formation in patients with blunt hepatic injury after non-operative management. AB - PURPOSE: To identify risk factors for liver abscess formation in patients with blunt hepatic injury who underwent non-operative management (NOM). METHODS: From January 2004 to October 2008, retrospective data were collected from a single level I trauma center. Clinical data, hospital course, and outcome were all extracted from patient medical records for further analysis. RESULTS: A total of 358 patients were enrolled for analysis. There were 13 patients with liver abscess after blunt hepatic injury. Patients with abscess had a significant increase in glutamic oxaloacetic transaminase (GOT, p = 0.006) and glutamic pyruvic transaminase (GPT, p < 0.0001), and a decrease in arterial blood pH (p = 0.023) compared to patients without abscess in the univariate analyses. In addition, high-grade hepatic injury and transarterial embolization (TAE, p < 0.001) were also risk factors for liver abscess formation. Five factors (GOT, GPT, pH level in the arterial blood sample, TAE, and high-grade hepatic injury) were included in the multivariate analysis. TAE, high-grade hepatic injury, and GPT level were statistically significant. The odds ratios of TAE and high-grade hepatic injury were 15.41 and 16.08, respectively. A receiver operating characteristic (ROC) analysis was used for GPT, and it suggested cutoff values of 372.5 U/L. A prediction model based on the ROC analysis had 100 % sensitivity and 86.7 % specificity to predict liver abscess formation in patients with two of the three independent risk factors. CONCLUSIONS: TAE, high-grade hepatic injury, and a high GPT level are independent risk factors for liver abscess formation. PMID- 26814511 TI - The role of non-invasive ventilation in blunt chest trauma: systematic review and meta-analysis. AB - PURPOSE: Respiratory support is the mainstay for the management of patients with pulmonary contusion following blunt chest trauma. In patients not requiring immediate intubation and ventilation, the optimal respiratory management strategy is not clear. This systematic review and meta-analysis aimed to determine the efficacy of non-invasive ventilation (NIV), as compared to traditional respiratory support strategies (i.e., high-flow facemask oxygen or pre-emptive intubation and ventilation), in adult patients with blunt chest trauma. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing NIV to traditional forms of respiratory support (i.e., facemask oxygen or intubation and ventilation) in an adult trauma population. For each eligible trial, we extracted the outcomes of all-cause mortality, length of intensive care unit (ICU) stay, length of hospital stay, and pneumonia. RESULTS: We identified 643 citations, selected 17 for full-text evaluation, and identified three eligible RCTs. Patients receiving NIV had a non-significant reduction in the risk of death (OR 0.55; 95 % CI 0.18-1.70; I (2) = 0 %), but significant reductions in length of ICU stay (mean difference -2.45 days; 95 % CI -4.27 to 0.63; I (2) = 66 %), length of hospital stay (mean difference -4.60 days; 95 % CI -8.81 to -0.39; I (2) = 85 %), and risk of pneumonia (OR 0.20; 95 % CI 0.09-0.47; I (2) = 0 %). CONCLUSION: This meta-analysis suggests that NIV is superior to both high-flow facemask oxygen or pre-emptive intubation and ventilation in patients with blunt chest trauma who have no contraindication to NIV. PMID- 26814512 TI - Adherence to protocol in pregnant trauma patients? A 12-year retrospective study. AB - PURPOSE: We investigated whether the standard (ATLS) trauma protocol was adhered to in cases of suspected multi-traumatized pregnant patients and if serious injuries were overlooked. We hypothesized that radiographic studies would be less frequent in pregnant trauma patients. METHODS: Forty-eight pregnant trauma patients were received in the observational period from January 2000 until May 2012; median age 30 years (range 16-40) and median stage of pregnancy 22 weeks (range 4-40). A retrospective review of patient files was performed. RESULTS: Twenty-one percent of the pregnant trauma patients received a full trauma CT (T CT) scan (head to pelvis), which was significantly lower than the percentage (62 %) of all primarily referred trauma patients in the same period. In the last four years of observation, the use of radiographic studies among pregnant trauma patients increased considerably. Along with this increase in the tendency to use T-CT over time during the observational period, there was also a rise in the median ISS. In addition, radiographic studies of the pelvis and abdominal area were performed only half as frequently as studies of the neck and chest. CONCLUSIONS: Adherence to the ATLS protocol in pregnant trauma patients was low in relation to radiographic studies but, in spite of this, no known significant injuries were missed. We found that a pelvic fracture seems to be predictive of a high risk of obstetric complications, such as intrauterine death or the need for cesarean section, but we were not able to relate trauma in general to a higher risk of cesarean section or premature birth. PMID- 26814513 TI - Age and mortality after injury: is the association linear? AB - INTRODUCTION: Multiple studies have demonstrated a linear association between advancing age and mortality after injury. An inflection point, or an age at which outcomes begin to differ, has not been previously described. We hypothesized that the relationship between age and mortality after injury is non-linear and an inflection point exists. METHODS: We performed a retrospective cohort analysis at our urban level I center from 2007 through 2009. All patients aged 65 years and older with the admission diagnosis of injury were included. Non-parametric logistic regression was used to identify the functional form between mortality and age. Multivariate logistic regression was utilized to explore the association between age and mortality. Age 65 years was used as the reference. Significance was defined as p < 0.05. RESULTS: A total of 1,107 patients were included in the analysis. One-third required intensive care unit (ICU) admission and 48 % had traumatic brain injury. 229 patients (20.6 %) were 84 years of age or older. The overall mortality was 7.2 %. Our model indicates that mortality is a quadratic function of age. After controlling for confounders, age is associated with mortality with a regression coefficient of 1.08 for the linear term (p = 0.02) and a regression coefficient of -0.006 for the quadratic term (p = 0.03). The model identified 84.4 years of age as the inflection point at which mortality rates begin to decline. CONCLUSIONS: The risk of death after injury varies linearly with age until 84 years. After 84 years of age, the mortality rates decline. These findings may reflect the varying severity of comorbidities and differences in baseline functional status in elderly trauma patients. Specifically, a proportion of our injured patient population less than 84 years old may be more frail, contributing to increased mortality after trauma, whereas a larger proportion of our injured patients over 84 years old, by virtue of reaching this advanced age, may, in fact, be less frail, contributing to less risk of death. PMID- 26814514 TI - The impact of body mass index and gender on the development of infectious complications in polytrauma patients. AB - PURPOSE: The aim was to test the impact of body mass index (BMI) and gender on infectious complications after polytrauma. METHODS: A total of 651 patients were included in this retrospective study, with an Injury Severity Score (ISS) >=16 and age >=16 years. The sample was subdivided into three groups: BMI <25 kg/m(2), BMI 25-30 kg/m(2), and BMI >30 kg/m(2), and a female and a male group. Infectious complications were observed for 31 days after admission. Data are given as mean +/- standard errors of the means. Analysis of variance, Kruskal-Wallis test, chi(2) tests, and Pearson's correlation were used for the analyses and the significance level was set at P < 0.05. RESULTS: The overall infection rates were 31.0 % in the BMI <25 kg/m(2) group, 29.0 % in the BMI 25-30 kg/m(2) group, and 24.5 % in the BMI >30 kg/m(2) group (P = 0.519). The female patients developed significantly fewer infectious complications than the male patients (26.8 vs. 73.2 %; P < 0.001). The incidence of death was significantly decreased according to the BMI group (8.8 vs. 7.2 vs. 1.5 %; P < 0.0001) and the female population had a significantly lower mortality rate (4.1 vs. 13.4 %; P < 0.0001). Pearson's correlations between the Abbreviated Injury Scale (AIS) score and the corresponding infectious foci were not significant. CONCLUSION: Higher BMI seems to be protective against polytrauma-associated death but not polytrauma associated infections, and female gender protects against both polytrauma associated infections and death. Understanding gender-specific immunomodulation could improve the outcome of polytrauma patients. PMID- 26814515 TI - A randomized trial comparing two intraosseous access devices in intrahospital healthcare providers with a focus on retention of knowledge, skill, and self efficacy. AB - INTRODUCTION: Intraosseous access is recommended in vitally compromised patients if an intravenous access cannot be easily obtained. Intraosseous infusion can be initiated by various healthcare providers. Currently, there are two mechanical intraosseous devices approved by the U.S. Food and Drug Administration (FDA) for use in adults and children. A comparison is made in this study of the theoretical and practical performance by anesthesiologists and registered nurses of anesthesia (RNAs) in the use of the battery-powered device (device A) versus the spring-loaded needle device (device B). This study entailed a 12-month follow-up of knowledge, skill retention, and self-efficacy measured by standardized testing. METHODS: A prospective randomized trial was performed, initially comparing 15 anesthesiologists and 15 RNAs, both on using the two types of intraosseous devices. A structured lecture and skill station was given with the educational aids provided by the respective manufacturers. Individual knowledge and practical skills were tested at 0, 3, and 12 months after the initial course. RESULTS: There was no statistical significant difference in the retention of theoretical knowledge between RNAs and anesthesiologists on all testing occasions. However, the self-efficacy of the anesthesiologists is significantly higher (p < 0.01) than the self-efficacy of the RNAs for both devices, on any testing occasion. Insufficient skills were local disinfection (both groups, both devices) and attachment of the needle to the intravenous line (RNAs with both devices). In 33 % of all device B handlings, unsafe practice occurred. CONCLUSION: The use of device A is safer in handling in comparison to device B at 12 months follow-up. The hypothesis that doctors are more qualified in obtaining intraosseous access has been disproven, as anesthesiologists were as successful as RNAs. However, the low self-efficacy of RNAs in the use of intraosseous devices could diminish the chance of them actually using one. PMID- 26814516 TI - Titanium osteosynthesis hardware in maxillofacial trauma surgery: to remove or remain? A retrospective study. AB - INTRODUCTION: A 5-year retrospective study evaluated the incidence and causes for removal of titanium miniplates. MATERIAL AND METHODS: The surgical records of 156 patients treated with rigid internal fixation after maxillofacial traumas were reviewed. Study variables included age, sex, site of fracture, site and number of plates, time of plate removal and reasons for plate removal. RESULTS: Of 384 plates used for fixation, 35 plates (9 %) in 21 patients (13.5 %) were removed due to hardware related complications. Statistical significance (p < 0.01) was observed in mandibular body and parasymphysis fractures with regards to both fracture site location and plate removal rates. Most plates were removed within the first year after placement (p < 0.01). The highest number of fractures were observed in the 20-30 years group (p < 0.01) while most cases of removal were in the 30-40 years group (p < 0.01). Secondary reconstruction/growth facilitation (11/156, 7 %) (p < 0.01) was the main cause of plate removal while infection/wound dehiscence (9/156, 6 %) (p < 0.01) was the main cause for complication related plate removal. A significantly greater number of plates placed via intraoral incisions (p < 0.01) needed removal. CONCLUSIONS: The low incidence of complication related plate removal (7 %) in the mid and upper face in this study suggests that routine removal of asymptomatic titanium miniplates after maxillofacial trauma at these sites may not be beneficial. The high rate of mandibular site complications (19 %) in this study suggests that routine removal of titanium hardware from mandibular sites may be indicated. PMID- 26814517 TI - A measuremental approach to calcaneal fractures. AB - OBJECTIVE: The calcaneus is the most frequently broken tarsal bone in the setting of trauma. The diagnosis, treatment and prognosis of calcaneal fractures depend on the location and type determined by the Sanders classification. With the help of measurements on lateral view radiographs like the Bohler's angle, the angle of Gissane, the calcaneal inclination angle and the calcaneal facet height, we can predict the severity of the trauma and prognosis by assessing the collapse of the calcaneus. On computed tomography (CT), calcaneal fractures which reach into the joint space can be classified by the Sanders classification system according to the number of fragments. In this study, we tried to determine whether calcaneal fracture severity determined by angle and facet height measurements on lateral X ray radiographs correlate with the Sanders classification. MATERIALS AND METHODS: Among 69 patients diagnosed with calcaneal fractures, we performed a retrospective study by analysing the Bohler's angle, the angle of Gissane, the calcaneal inclination angle and the calcaneal facet height on digital lateral X rays and by classifying the fractures according to the Sanders classification by CT. We compared the results of the two different imaging modalities. RESULTS: We found that, as the Sanders classification type became more severe from type 1 to type 4, a general decrease was observed in the Bohler's angle, the inclination angle and the facet length, whereas a general increase was observed for the mean values of the angle of Gissane. CONCLUSION: These findings suggest that measurements obtained from lateral X-rays coincide with the Sanders classification and, therefore, might indicate the prognosis. PMID- 26814518 TI - Crossover external fixator for acetabular fractures: a cadaver study. AB - BACKGROUND: Dislocated acetabular fractures in polytraumatized patients are very challenging cases to deal with. Temporary stabilization by skeletal traction is difficult in these patients. A more effective solution can be an external fixation. OBJECTIVE: The authors designed a new crossover external fixation frame for acetabular fracture. The aim of this study is the biomechanical testing of this frame on human cadavers. METHODS: This study is an experiment on ten human cadavers. The acetabular fracture C2.2 was created. The stabilization effect of external fixation was compared with stabilization by large distractor. Femoral heads' shifts caused by standardized manipulation with the cadaver were obtained from X-ray pictures. RESULTS: The mean total shift in stabilization technique by external fixation was 2.56 (1-4) mm. In stabilization by large distractor, the mean of the total shift after cadaver manipulation was 5.11 (0-10) mm. No significant differences were found between stabilization by external fixation and by large distractor (p = 0.066). CONCLUSIONS: The stabilization of acetabular fracture C2.2 by a crossover external fixator is as effective as large distractor. The crossover external fixation could be a suitable solution for the temporary stabilization of acetabular fractures in polytraumatized patients. Subsequent studies including clinical trials are necessary to confirm the authors' suggestion. PMID- 26814519 TI - Posterior only versus combined posterior and anterior approaches in surgical management of lumbosacral tuberculosis with paraspinal abscess in adults. AB - PURPOSE: To compare single-stage posterior transforaminal lumbar interbody fusion, debridement, posterior instrumentation, and postural drainage (posterior only surgery) with a combined posterior-anterior surgical approach for treatment of adults with lumbosacral spinal tuberculosis (STB) with paraspinal abscess and to determine the clinical feasibility and effectiveness of posterior-only surgical treatment. METHODS: Thirty-nine patients with lumbosacral STB and paraspinal abscess were treated with one of two surgical procedures in our center from September 2003 to December 2012. Nineteen patients were treated with posterior-only surgery (Group A) and 20 were treated with combined posterior anterior surgery (Group B). Surgery duration, intraoperative blood loss, length of hospitalization, bony fusion rates, complication rates, neurological status, lumbosacral angle correction, and Kirkaldy-Willis functional outcomes of the two groups were compared. RESULTS: The average follow-up period was 39.1 +/- 12.0 months for Group A and 40.7 +/- 12.4 months for Group B. Under the Frankel classification, all patients improved with treatment. STB was completely cured and grafted bones were fused within 5-11 months in all patients. There were no persistent or recurrent infections or obvious differences in radiological results between the groups. The lumbosacral angle was significantly corrected after surgical management, but loss of correction was seen in both groups. The average operative duration, blood loss, length of hospital stay, and postoperative complication rate of Group A were lower than those of Group B. CONCLUSIONS: Posterior-only surgery is feasible and effective, resulting in better clinical outcomes than combined posterior-anterior surgeries, especially in surgical time, blood loss, hospital stay, and complications. PMID- 26814521 TI - ESTES News 5.2014. PMID- 26814520 TI - Risk stratification, management and outcomes in emergency general surgical patients in the UK. AB - INTRODUCTION: The Royal College of Surgeons of England (RCS) published guidance in 2011 setting standards for the management of emergency surgical patients with the aim of reducing surgical mortality. These suggested the presence of a consultant surgeon and anaesthetist, and transfer to a higher level of care postoperatively for all patients deemed high risk. OBJECTIVE: This prospective multi-institutional study sought to evaluate whether adherence to these standards was associated with reduced mortality. DESIGN: Data were prospectively collected on all emergency general surgery operations performed in emergency theatres across Merseyside, UK, during a 30-day period in September-October 2011. Patients were risk assessed using P-POSSUM (Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity). High-risk patients were classified as those with a P-POSSUM predicted mortality of >=10 %, and moderate-risk patients as those with a P-POSSUM predicted mortality of 5-10 %. RESULTS: Some 494 procedures were performed on 471 patients. Twenty-four patients (5 %) died within 30 days of surgery. Mortality in the 65 patients identified as high risk was 27 % (14 patients undergoing 17 procedures), with a consultant surgeon present in 46 of 65 high-risk cases (71 %), a consultant anaesthetist in 43 (66 %), and 46 (71 %) cases were admitted to level 2 or 3 care postoperatively. There was no association between adherence to standards and postoperative mortality in either the whole cohort or specifically the high-risk group. CONCLUSIONS: There is currently incomplete adherence to the national guidelines, but this does not seem to adversely impact postoperative mortality. PMID- 26814522 TI - Emergency aeromedical services in Ireland: a retrospective study for "MEDEVAC112". AB - AIM: This is a retrospective analysis of all consecutive patients requiring emergency aeromedical services (EAS) to a level II trauma centre. This analysis was performed to evaluate the new service to Tallaght Hospital in terms of: the criteria used for dispatch, an estimate of baseline efficiency of time critical management of patients, the cross-catchment transfer of patients. METHODS: Data were provided by the EAS with respect to the patients brought to Tallaght Hospital not including inter-facility transfers for the calendar year 2013. Using this information patient records were matched to the electronic database. Once patients were identified, their hospital journey was catalogued using chart review. Using Google Maps and the EAS data an estimated road-time was calculated. Specific dispatch criteria were unavailable, however, using five broad categories outlined by the American College of Surgeons (ACS) for trauma related dispatch criteria each case was evaluated. RESULTS: The EAS data had 52 cases which were reported to come to this unit. 48 patient records were accurately matched to this data. 25 % were discharged without speciality input. Seven patients died within 24 h only one of which was admitted under a speciality. 30 patients were admitted under specialist care with two requiring transfer to another centre. 80 % of admissions came under the primary management of the orthopaedic team. 11 patients required operative management, five required ICU management, three required chest drains and one patient required cardiac angiogram. Of the five dispatch criteria categories evaluated the mean number of criteria met was 3.1. CONCLUSION: 25 % of the patients were managed in the Emergency Department alone indicating an acceptable level of over-triage according to ACS guidelines. When comparing the dispatch criteria met for this 25 % there was no statistical difference compared with the other 75 %. Sensitivity and specificity analyses have looked at the question of dispatch criteria before and our data are comparable with international evidence. We suggest that further research be undertaken to develop this service to improve activation criteria and thereby the entire service delivered. PMID- 26814523 TI - Soft Tissue and Bone Reconstruction in Severe Open Fractures of the Lower Extremity. PMID- 26814524 TI - How to Cover Soft-Tissue Defects After Injuries to the Leg in Precarious Conditions. AB - BACKGROUND: In precarious conditions, bone exposure on the leg is synonymous with amputation. The authors describe their experiences with such injuries in 15 patients. MATERIALS AND METHODS: Fifteen patients were operated by the same surgeon in Afghanistan and Ivory Coast for bone exposure on the leg after war or roadcrash injuries. A flap was performed after an initial debridement and external fixation. The delay between the flap and the first injury was about 42 days. RESULTS: The duration of hospitalization following the flap was about eight days. Cicatrization was complete after 25 days. Three patients had complications: one partial necrosis of the skin, one sepsis, and one patient had a leg amputation. DISCUSSION: In precarious conditions, the management of bone exposure in local civilians and soldiers is limited by the conditions in their country or the conditions at the field hospital. The treatment must be simple and reliable because it may be difficult to perform patient follow-up. A pedicled flap provides new vascularized tissue with anti-infectious properties. Classical indications are: muscular flaps for the proximal and the middle part of the leg; sural flaps for the middle and the distal-third part. In substantial soft-tissue defects, amputation must be discussed. CONCLUSION: The pedicled flap is an essential technique for fighting against infection, especially in cases where only poor technical and medicinal resources are available. This simple and reliable technique allows most tissue defects on the leg to be covered. PMID- 26814525 TI - Soft Tissue Management in Open Fractures of the Lower Leg: The Role of Vacuum Therapy. AB - The management of severe open fractures of the lower leg continues to challenge the treating surgeon. Major difficulties include high infection rates as well as adequate temporary soft tissue coverage. In the past, these injuries were commonly associated with loss of the extremity. Today, vacuum therapy provides not only safe temporary wound coverage but also conditioning of the soft tissues until definitive wound closure. Amongst other advantages, bacterial clearance and increased formation of granulation tissue are attributed to vacuum therapy, making it an extremely attractive tool in the field of wound healing. However, despite its clinical significance, which is underlined by a constantly increasing range of indications, there is a substantial lack of basic research and well designed studies documenting the superiority of vacuum therapy compared to alternative wound dressings. Vacuum therapy has been approved as an adjunct in the treatment of severe open fractures of the lower leg, complementing repeated surgical debridement and soft tissue coverage by microvascular flaps, which are still crucial in the treatment of these limb-threatening injuries. Vacuum therapy has in general proven useful in the management of soft tissue injuries and, since it is generally well tolerated and has low complication rates, it is fast becoming the gold standard for temporary wound coverage in the treatment of severe open fractures of the lower leg. PMID- 26814526 TI - Reconstruction of Large Diaphyseal Defects of the Femur and the Tibia with Autologous Bone. AB - Post-traumatic segmental bone defects of the femur and the tibia above the critical size require special attention because conventional bone grafts result in high rates of nonunion. The biological and biomechanical aspects of this challenging surgery, as well as ongoing refinements to achieve mechanically stable bone healing with correct bone alignment are reviewed. Choosing the best appropriate method is mainly dependent on both the location and etiology of the bone defect. Three patients with successful bone reconstruction using two-stage reconstruction with cancellous bone graft, double-barrel free vascularized fibula transfer and distraction osteogenesis are described. Advantages and disadvantages of these methods are discussed in accordance with recent literature. PMID- 26814527 TI - Hemorrhage is More Prevalent than Brain Injury in Early Trauma Deaths: The Golden Six Hours. AB - INTRODUCTION: Under the trimodal distribution, most trauma deaths occur within the first hour. Determination of cause of death without autopsy review is inaccurate. The goal of this study is to determine cause of death, in hourly intervals, in trauma patients who died in the first 24 h, as determined by autopsy. MATERIALS AND METHODS: Trauma deaths that occurred within 24 h at a Level I trauma center were reviewed over a six-year period ending December 2005. Timing of death was separated into 0-1, 1-3, 3-6, 6-12 and 12-24 h intervals. Cause of death was determined by clinical course and AIS scores, and was confirmed by autopsy results. RESULTS: Overall, 9,388 trauma patients were admitted, of which 185 deaths occurred within 24 h, with 167 available autopsies. Blunt and penetrating were the injury mechanisms in 122 (73%) and 45 (27%) patients, respectively. Of 167 deaths, 73 (43.7%) occurred within the first hour. Brain injury, when compared to other body areas, was the most likely cause of death in all hourly intervals, but hemorrhage was as or more important than brain injury as the cause of death during the first 3 h and up to 6 h. No deaths were attributable to hemorrhage after 12 h. CONCLUSIONS: The temporal distribution of the cause of death varies in the first 24 h after admission. Hemorrhage should not be overlooked as the cause of death, even after survival beyond 1 h. Understanding the temporal relationship of causes of early death can aid in the targeting of management and surgical training to optimize patient outcome. PMID- 26814528 TI - Is Routine Spiral CT-Chest Justified in Evaluation of the Major Blunt Trauma Patients? AB - STUDY: New generation spiral CT scanners permit multiple consecutive CT examinations on the same trauma patient in a short period of time. The purpose of this study was to evaluate the diagnostic role and therapeutic impact of routine spiral CT chest in multiply injured patients or patients with a suspicious mechanism of injury. PATIENTS AND METHODS: This prospective study included 443 patients with blunt chest trauma. All patients underwent a spiral CT chest as part of their routine evaluation. Radiological interpretation of chest x-rays, CT scan findings, and changes in management plan guided by these findings were recorded. RESULTS: The mechanism of injury was road traffic accidents in 422 patients (95.26%). Out of the 167 patients with normal chest radiograph, 136 (81.43%) were found to have an abnormality on chest CT. The management was changed in the form of additional investigations or unplanned intervention in 92 patients (20.76%). Additional investigations included transoesophageal echocardiography (n = 7), bronchoscopy (n = 13), transfer to higher center for aortography (n = 2). Intercostal tubes (n = 55), thoracotomies (n = 4), fixation of sternal fracture (n = 9), laparotomy (n = 1) and spinalfixation (n = 1) were performed following the CT scan. CONCLUSION: Although the incidence of significant injuries identified by the chest CT scan was low, it did prompt immediate intervention in a significant number of patients; some of them had potentially life-threatening injuries. Routine use of CT scanning is warranted in early evaluation of polytrauma patients or patients with severe blunt chest trauma. PMID- 26814529 TI - Minimal Invasive PHILOS((r))-Plate Osteosynthesis in Proximal Humeral Fractures. AB - INTRODUCTION: The anterior delto-pectoral approach is the standard approach for the fixation of proximal humeral fractures with the PHILOS((r))-Plate system. However, this approach can impair the vascular supply and can increase avascular necrosis. The objective of this study was to evaluate the results and complexity of surgery of proximal humeral fractures with a minimal invasive (MIPO) approach. METHODS: All PHILOS((r))-plate osteosynthesis operated between Januray 2003 and June 2006 were evaluated prospectively. A minimal invasive antero-lateral deltasplit-approach was performed in all two to four fragment instable fractures meeting the indication for osteosynthesis according to Neer. An open approach (ORIF) was chosen in all other fractures mainly dislocated fractures and particularly in fractures with major subcapital displacement. RESULTS: A cohort of 68 patients suffered a proximal humerus fracture and qualified for a minimal invasive approach with a PHILOS((r))-plate osteosynthesis. Of these 68 patients, 41 were locally resident. Eight patients refused a follow-up, two patients were in constant care, and two patients died; 29 patients (71%) (20 females, 9 males) could be documented entirely with a median age of 64 years. The median operation time amounted to 75 min with a fluoroscopic time of 160 s. The median Constant score was 78 after 12 months. All fractures healed in adequate time. One patient showed a lesion of the ventral part of the axillary nerve. No patient suffered an avascular necrosis. DISCUSSION: The minimal invasive PHILOS((r)) plate osteosynthesis through an antero-lateral delta-split approach proved to be an elegant procedure for selected fractures of the proximal humerus with a low morbidity and good functional outcome. PMID- 26814530 TI - Clinical Risk Factors for Hip Fracture in Young Adults Under 50 Years Old. AB - BACKGROUND: Established risk factors for hip fracture exist for older individuals. Young adults (less than 50 years old) presenting with hip fractures have received little attention. METHODS: The records of all adults, presenting over a 5-year period (1999-2004), to a large inner city teaching hospital, with a diagnosis of hip fracture, were reviewed. Of the 2,778 subjects, 196 involved people less than 65 years of age, limiting this to those less than 50 years old left 42 subjects [30 F/12 M, median (IQR) age 43 (37-47) years old]. Stepwise logistic regression analysis was performed to examine for clinical risk factors. RESULTS: In this cohort regression analysis revealed a history of high impact trauma (beta = 0.219, p = 0.002) and intravenous drug abuse (beta = 0.206, p = 0.003) as predictors for risk of hip fracture. CONCLUSIONS: Our data suggest that intravenous drug abusers under 50 are a particular group that we should be targeting for intervention strategies. PMID- 26814531 TI - Historical Treatment Results of Pelvic Ring Fractures: A 12-year Cohort Study. AB - BACKGROUND: Since the Academic Medical Center Amsterdam was appointed as a level 1 trauma center in July 1997, the number of polytrauma patients who were presented has increased. This stimulated us to perform a retrospective analysis on the treatment results of patients with a pelvic ring fracture and to evaluate our treatment strategies. MATERIALS AND METHODS: A chart review of all patients with a partially stable fracture (Tile/AO type B) or an unstable fracture (Tile/AO type C) was performed. All patients presented between 1 January 1990 and 31 December 2001 were included. Two historical groups (1990-1997 and 1998-2001) were formed. General demographics, treatment method, complications, re operations, length of hospital stay and anatomic results were recorded for all patients. RESULTS: Fifty-two patients were included in group 1 and 65 patients in group 2. There was a lower mortality in group 2. The B-fractures were treated either conservatively (group 1 83.3% vs. group 2 73.8%), by external fixation (16.7 vs. 9.5%) or by ORIF (0 vs. 16.7%). C-fractures were treated by ORIF in 32.1 versus 82.6%, by external fixation in 28.6 versus 4.4% and conservatively 39.3 versus 13.0%, respectively. Fracture healing with less than 10 mm displacement was achieved in 58.3 versus 78.6% for the B-fractures, while this was achieved in 42.9 versus 73.9% in the C-fractures. Group 2 showed significantly fewer complications. CONCLUSION: Evaluating two consecutive patient groups shows an increase in the number of fractures. A more aggressive surgical treatment has lead to lower mortality, improved anatomical reduction, and lower rate of complications. PMID- 26814532 TI - The Value of the Trauma Mechanism in the Triage of Severely Injured Elderly. AB - BACKGROUND: The triage of trauma patients is currently based on the trauma mechanism. However, it is known that elderly patients can sustain severe injuries due to insignificant trauma mechanisms. As such, triage methods might be questionable. OBJECTIVE: To evaluate whether current trauma triage criteria are appropriate in severely injured elderly patients. METHODS: To analyze the effect of the trauma mechanism on triage and treatment, consecutive patients >= 55 years of age, with an injury severity score > 15, treated from 2002 to 2005 were divided into those who sustained a high-energy trauma (HET) versus a low energy trauma (LET). Pre-hospital and in-hospital data, injury characteristics, and data on mortality and disablement one year postinjury (sickness impact profile) were analyzed for HET and LET groups. RESULTS: Age, sex and co-morbidity rate were similar in 84 HET patients and 107 LET patients. HET patients (mean ISS 28) received more sophisticated trauma care than LET patients (mean ISS 22), although mortality was similar (38 vs. 34%). Long-term disablement was also similar (median SIP scores 4 vs. 6). Severe head injuries and the Revised Trauma Score were related to mortality. Physical disablement was related to preexisting co morbidities. No variables were related to psychosocial disablement. CONCLUSIONS: In elderly people a low energy trauma may lead to severe consequences. Not only the trauma mechanism, but also age, co-morbidity, and the likelihood of a brain injury should be leading in the triage and subsequent management of severely injured elderly. PMID- 26814533 TI - Evaluation of Quality of Trauma Care in a Local Hospital Using a Customization of ASCOT. AB - OBJECTIVE: Evaluating processes of care and outcomes of injured patients are important if improvements in the quality of care delivered to injured patients are to be accomplished. We applied a customized ASCOT model developed from our database as a tool to criticize the quality of care in a local hospital. PATIENTS AND METHODS: A total number of 4,096 trauma patients were used to develop new coefficients for customization of ASCOT. These patients were divided randomly into two equal groups. New coefficients for ASCOT were derived from the first set of patients. The newly developed model was validated in the second group of patients and the measures of discrimination (area under the ROC curve) and calibration (Hosmer-Lemeshow goodness of fit) were calculated. Then we used the customized model to calculate the W score in different subgroups of patients treated in a local hospital to evaluate the care offered to patients in each group. RESULTS: The customized ASCOT had a good discrimination (area under ROC curve = 0.9575) and calibration (Hosmer-Lemeshow goodness of fit p value = 0.7628) in the validation dataset. Using the customized model, we calculated W score in different subgroup of patients treated in a local hospital for a period of six months. The quality of care was worst for laparotomy (W = -13.31) and pelvic fracture (W = -5.56) and best for orthopedic (W = 1.76) operations. CONCLUSION: We believe that a customization of ASCOT model when used for evaluation of quality of care in a local hospital can be useful for detection of defects and improvement of the process of care delivered to the patients. PMID- 26814535 TI - Traumatic Cervical Vertebral Artery Transection Associated with a Dural Tear Leading to Subarachnoid Extravasation. AB - Vertebral artery injuries can be seen following trauma. Most traumatic vertebral artery injuries are limited to an intimal dissection. Rarely, transection of the vertebral artery can be seen with extravasation of hemorrhage into the surrounding soft tissues of the neck. Dural tears are rare in the setting of trauma. They are usually the result of penetrating trauma or severe blunt trauma. We present a case with both a vertebral artery transection and a dural tear. The combination of these lethal injuries resulted in extravasation of hemorrhage into the soft tissues of the neck, through the dural tear, and into the subarachnoid space of the cervical spine. The subarachnoid hemorrhage extended superiorly into the brain. The diagnosis was made by computed tomography (CT) and computed tomography angiography (CTA). The treatment of traumatic vertebral artery transections and dural tears are discussed. PMID- 26814534 TI - Cost-Drivers in Acute Treatment of Severe Trauma in Europe: A Systematic Review of Literature. AB - INTRODUCTION: Throughout the world, trauma is a leading cause of morbidity and mortality in the young and most active group of society. While specialist trauma centers play a critical role in the survival after severe trauma, the assessment of trauma-related costs, budgeting for adequate trauma capacity, and determining the cost-effectiveness of interventions in critical care are fraught with difficulties. Through a systematic review of the European literature on severe trauma, we aimed to identify the key elements that drive the costs of acute trauma care. METHODS: A PubMed/MEDLINE search for articles relating the costs and economics of trauma was performed for the period January 1995 to July 2007. One hundred and seventy-three European publications were identified. Twelve publications were retrieved for complete review that provided original cost data, a breakdown of costs according to the different elements of trauma care, and focused on severe adult polytrauma. The identified publications presented studies from the UK (3), Germany (6), Italy (2), and Switzerland (1). RESULTS: In all publications reviewed, length of stay in the intensive care unit (ICU; 60%) and requirements for surgical interventions (<= 25%) were the key drivers of hospital costs. The cost of transfusion during the initial rescue therapy can also be substantial, and in fact represented a significant portion of the overall cost of emergency and ICU care. Multiple injuries often require multiple surgical interventions, and prolonged ICU and hospital stay, and across all studies a clear relationship was observed between the severity of polytrauma injuries observed and overall treatment costs. While significant differences existed in the absolute costs of trauma care across countries, the key drivers of costs were remarkably similar. CONCLUSIONS: Irrespective of the idiosyncrasies of the national healthcare systems in Europe, severity of injury, length of stay in ICU, surgical interventions and transfusion requirements represent the key drivers of acute trauma care for severe injury. PMID- 26814536 TI - Giant Synovial Cyst of the Anterior Compartment: An Unusual Cause of Chronic Knee Pain After Trauma. AB - There is almost no literature describing the management and rationale for intervention for posttraumatic, extra-articular synovial cysts of the knee. We describe the very rare case of a 45-year-old blind man who developed chronic knee pain after a traumatic injury. He was found to have a giant, posttraumatic, true synovial cyst of the knee in an extra-articular location and migrating down the anterior compartment. The surgical management, potential complications, and rationale for intervention are discussed. PMID- 26814537 TI - Compartment Syndrome of the Arm After Cable-Wakeboard Accident. AB - A compartment syndrome is an increased tissue pressure within a closed osteofascial compartment. This compromises blood flow to the muscles and nerves within that compartment, which -if not treated adequately in an early stage results in permanent tissue and nerve damage. It most frequently occurs in the lower leg, but can also occur elsewhere when muscles are enclosed in tight fascial compartments, such as the forearm and hand. In this report a patient is described who developed an acute compartment syndrome of the arm after a cable wakeboard accident in which his arm was strangulated. Cable-wakeboarding is an extreme sport that has become very popular over the last years. Early recognition and treatment of an acute compartment syndrome is of extreme importance since in short term necrotic muscles can lead to severe irreversible complications. Accidents with cable-wakeboarding often occur during the start. This is caused by the strong forces that are on the cable during the start. Strangulation injuries of the arm can cause a compartment syndrome of the arm. Possibly a wet-suit or dry-suit offers some protection. However, the duration of strangulation determines much of the damage. Although diagnosis of a compartment syndrome can be difficult, a high index of suspicion combined with fast and adequate treatment with a fasciotomy improve outcome and prognosis. PMID- 26814538 TI - Irreducible Pulled Elbow in an Adolescent. A Case Report. AB - We present a case of pulled elbow in an adolescent patient that required open reduction. PMID- 26814539 TI - Simultaneous, Bilateral Pathological Displaced Intracapsular Hip Fractures Occurring Spontaneously Secondary to Osteomalacia of Hypomagnesemic Origin: A Case Report and Review of the Literature. AB - Spontaneous fractures involving both of the femoral necks simultaneously are exceedingly rare events. We report a case of an elderly female who presented after breaking both femoral necks following a trivial fall, initially diagnosed as age-related osteoporosis. Both the hips were treated by hemiarthroplasty. The diagnosis was revised to vitamin D-resistant osteomalacia secondary to hypomagnesemia after histopathological confirmation and further investigations. We examine the different etiological factors and mechanisms operating in the causation of this rare injury and explore the possible role of magnesium in the pathogenesis of osteomalacia. Fractures may remain occult until late, leading to increased morbidity and mortality. The value of an early MRI is recapitulated, with emphasis placed on prevention and early fixation. PMID- 26814540 TI - Exploration of the effects of classroom humidity levels on teachers' respiratory symptoms. AB - PURPOSE: Previous studies indicate that teachers have higher asthma prevalence than other non-industrial worker groups. Schools frequently have trouble maintaining indoor relative humidity (RH) within the optimum range (30-50 %) for reducing allergens and irritants. However, the potential relationship between classroom humidity and teachers' health has not been explored. Thus, we examined the relationship between classroom humidity levels and respiratory symptoms among North Carolina teachers. METHODS: Teachers (n = 122) recorded daily symptoms, while data-logging hygrometers recorded classroom RH levels in ten North Carolina schools. We examined effects of indoor humidity on occurrence of symptoms using modified Poisson regression models for correlated binary data. RESULTS: The risk of asthma-like symptoms among teachers with classroom RH >50 % for 5 days was 1.27 (95 % Confidence Interval (CI) 0.81, 2.00) times the risk among the referent (teachers with classroom RH 30-50 %). The risk of cold/allergy symptoms among teachers with classroom RH >50 % for 5 days was 1.06 (95 % CI 0.82, 1.37) times the risk among the referent. Low RH (<30 %) for 5 days was associated with increased risk of asthma-like [risk ratio (RR) = 1.26 (95 % CI 0.73, 2.17)] and cold/allergy symptoms [RR = 1.11 (95 % CI 0.90, 1.37)]. CONCLUSIONS: Our findings suggest that prolonged exposure to high or low classroom RH was associated with modest (but not statistically significant) increases in the risk of respiratory symptoms among teachers. PMID- 26814542 TI - Editorial. PMID- 26814541 TI - Influence of Clinical Factors and Magnification Correction on Normal Thickness Profiles of Macular Retinal Layers Using Optical Coherence Tomography. AB - PURPOSE: To identify the factors which significantly contribute to the thickness variabilities in macular retinal layers measured by optical coherence tomography with or without magnification correction of analytical areas in normal subjects. METHODS: The thickness of retinal layers {retinal nerve fiber layer (RNFL), ganglion cell layer plus inner plexiform layer (GCLIPL), RNFL plus GCLIPL (ganglion cell complex, GCC), total retina, total retina minus GCC (outer retina)} were measured by macular scans (RS-3000, NIDEK) in 202 eyes of 202 normal Asian subjects aged 20 to 60 years. The analytical areas were defined by three concentric circles (1-, 3- and 6-mm nominal diameters) with or without magnification correction. For each layer thickness, a semipartial correlation (sr) was calculated for explanatory variables including age, gender, axial length, corneal curvature, and signal strength index. RESULTS: Outer retinal thickness was significantly thinner in females than in males (sr2, 0.07 to 0.13) regardless of analytical areas or magnification correction. Without magnification correction, axial length had a significant positive sr with RNFL (sr2, 0.12 to 0.33) and a negative sr with GCLIPL (sr2, 0.22 to 0.31), GCC (sr2, 0.03 to 0.17), total retina (sr2, 0.07 to 0.17) and outer retina (sr2, 0.16 to 0.29) in multiple analytical areas. The significant sr in RNFL, GCLIPL and GCC became mostly insignificant following magnification correction. CONCLUSIONS: The strong correlation between the thickness of inner retinal layers and axial length appeared to result from magnification effects. Outer retinal thickness may differ by gender and axial length independently of magnification correction. PMID- 26814543 TI - Therapeutic options for acute and chronic elbow instability. AB - INTRODUCTION: Acute elbow instability usually develops after injuries involving the bony or ligamentous stabilizers of the joint. It occurs frequently after dislocation and/or fracture-dislocation, but isolated valgus or varus overloading can also lead to ligament ruptures with subsequent instability. Chronic instability can result from incompletely healed acute injuries or from recurring microtrauma, for example after repetitive strain from participating in certain sports. CONCLUSION: Stable conditions of the joint are essential for early functional post-traumatic or postoperative treatment of the elbow, as permanent mobility deficits may result otherwise. The following article gives an overview of the current understanding of these injuries and concepts in treatment. PMID- 26814544 TI - Treatment of radial head and neck fractures: in favor of anatomical reconstruction. AB - Radial head fractures represent the most common elbow fractures. Undisplaced fractures usually occur in isolation and can be treated nonsurgically. Displaced fractures should be treated surgically. Simple two-part fractures can easily be handled by osteosynthesis, but comminuted fractures pose a major problem for reconstruction. As the radial head is an important stabilizer of the elbow joint especially in the context of concomitant ligamentous injuries-its resection may lead to pain, limited range of motion, and instability. Therefore, radial head resection is not recommended for the acute situation and open reduction internal fixation (ORIF) or prosthetic replacement should be aimed for. Complications such as secondary loss of fixation, radial head necrosis, and nonunion due to insufficient stability of the osteosynthesis have often been described. Therefore, prosthetic replacement is recommended if stable reconstruction is impossible. With the development of new locking plates especially designed for the maintenance of radial head fractures, the indications for osteosynthesis may be extended. As radial head fractures are complicated by a high percentage of ligamentous injuries and concomitant elbow fractures such as the coronoid, capitellum, and proximal ulna, these additional injuries have to be taken into account. The current treatment concepts are discussed within this paper. PMID- 26814545 TI - Distal humerus fractures in the elderly: osteosynthesis or endoprosthesis? Review of the literature. AB - Fractures of the distal humerus in adults are rare but challenging for the orthopaedic trauma surgeon. The bimodal distribution reflects the trauma mechanism. While distal humerus fractures are caused by high-energy traumata in young male adults, a fall from a standing height is the most common reason for humerus fractures among elderly females. As a rule, fractures of the distal humerus are treated surgically. In young patients, open reduction and internal fixation (ORIF) with anatomic locking plates are the gold standard. In elderly patients, reconstruction is not always possible, and total elbow arthroplasty (TEA) becomes necessary. The present article provides an overview of the current diagnostic and treatment recommendations. The current literature is reviewed and the results discussed. PMID- 26814546 TI - Endovascular repair of iatrogenic popliteal artery trauma. AB - PURPOSE: To evaluate the outcome of the management of iatrogenic arterial injuries following knee arthroplasty using a primary endovascular approach. METHODS: A detailed review of the management of all iatrogenic arterial injuries to the lower limb following total knee arthroplasty (TKA) referred to the Vascular Surgical Unit of a tertiary referral hospital between July 2005 and December 2007 identified from a prospectively maintained database. RESULTS: Of the seven cases referred over a 30-month period, six patients underwent endovascular treatment with successful limb salvage. All seven injuries were related to the popliteal artery behind the knee: pseudoaneurysm (4), intimal flap occlusion (2) and stenosis (1). One patient underwent above-knee amputation. The presentation and pattern of arterial injuries, potential risk factors for their occurrence, measures to reduce their risk and factors that aid in their early recognition are discussed. CONCLUSIONS: An endovascular approach may be considered for the management of these injuries, although it is likely to involve long-term surveillance and may not be appropriate for all cases. Surgeons performing TKA should be aware of the potential risk factors for arterial injury and maintain a high index of suspicion for these infrequent injuries during the post-operative period. PMID- 26814547 TI - Clinical outcomes following invasive versus noninvasive preoperative stabilization of closed diaphyseal femur fractures. AB - BACKGROUND: The use of invasive traction (INV-T) to stabilize femur fractures prior to fixation (open reduction and internal fixation, ORIF) remains controversial. Some centers have utilized noninvasive traction (NINV-T) or splinting preoperatively. It is possible that INV-T decreases hemorrhage. However, the use of INV-T in pediatric patients and for femoral neck fractures in adults is associated with worsened outcomes. We hypothesized that there is no difference in the need for transfusion between those who receive INV-T and NINV T. METHODS: A retrospective study was performed at two level I and one level II trauma center from January 2006 to December 2009. Patients >=18 years with a closed diaphyseal femur fracture who underwent ORIF within 48 h of arrival were included. Patients were grouped by method of preoperative fracture stabilization. Primary endpoint was need for transfusion. A power analysis found that 94 patients were needed to detect a 25 % difference with 80 % power. RESULTS: Fifty six (22 %) received INV-T and 199 (78 %) received NINV-T stabilization. No significant differences were found between groups in terms of age, injury severity score, or ORIF method. There was no significant difference between the two groups in the hemoglobin value on arrival, preoperative hemoglobin value, or the difference between admission and preoperative hemoglobin values. We did not find a significant difference in the need for red blood cell transfusion between the two groups. There was no difference in length of stay or discharge destination. CONCLUSION: INV-T is not associated with improved outcomes in adult patients with closed mid-shaft femoral fractures who are operated upon within 48 h of arrival. PMID- 26814548 TI - Minimally invasive plate osteosynthesis for distal radius fractures with a palmar locking plate. AB - PURPOSE: Since 2006, we have been performing minimally invasive plate osteosynthesis with a palmar locking plate and without division of the pronator quadratus muscle for repairing distal radial fractures. The purpose of this study was to present the surgical technique we have developed and to retrospectively evaluate the clinical outcomes. METHODS: Twenty patients were treated with this technique between January and December 2007. The range of motion of the wrist and forearm, grip strength, and the quick disability of the arm, shoulder, and hand score were assessed at the latest follow-up examination, and postoperative complications were evaluated. RESULTS: The average ranges of flexion and extension of the wrist were 55 degrees and 60 degrees , respectively. The average ranges of supination and pronation of the forearm were 88 degrees and 86 degrees , respectively. The average grip strength of the treated side was 71 % of that of the uninjured side. The average quick disability of the arm, shoulder, and hand score was 13.4 points. No patient had loss of fracture reduction, implant failure, deep infection, or tendon or nerve problems. CONCLUSIONS: The small skin incisions of this technique are advantageous from the aesthetic viewpoint. Minimally invasive plate osteosynthesis is one of the options for the treatment of distal radial fractures. PMID- 26814549 TI - Invasive and surgical procedures in pre-hospital care: what is the need? AB - BACKGROUND: On occasion, advanced invasive procedures in pre-hospital care can be life saving. This study aimed to identify the contemporary use of these procedures on a regional doctor-led air ambulance unit, and to define the need, skill set and training requirements for a regional pre-hospital team in the UK. METHODS: Mission data were recorded prospectively and the database reviewed to identify invasive procedures over a 76-month period. These cases were reviewed with indications, mechanism of injury, presence of cardiac arrest at any time point (+/-return of spontaneous circulation) and procedural failure or morbidity. RESULTS: Two hundred and thirty-five procedures were performed: 16 for injuries affecting the airway, 111 for breathing and 108 for circulation. Almost a third of patients in cardiac arrest regained spontaneous circulation. Procedures performed increased fivefold from 2003 to 2009, with a marked increase in the use of thoracostomy and intra-osseous access. Procedural failure or inadequacy was high with needle cricothyroidotomy, needle chest decompression and early intra osseous access experience. CONCLUSIONS: A steady increase in the number of procedures was observed over time. Less invasive methods of airway and breathing support were frequently inadequate, though definitive surgical airway or chest decompression was effective each time it was performed. Thoracotomy was performed infrequently. There are implications for the training of pre-hospital doctors who work in the majority of the UK. PMID- 26814550 TI - Predictors of early outcome after acute appendicitis: is delaying surgery for acute appendicitis an option? A retrospective study. AB - PURPOSE: This study analysed the clinical and para-clinical criteria that may allow surgeons and emergency physicians to take a decision regarding the surgery of acute appendicitis. METHODS: A retrospective analysis was conducted on 284 acute appendicitis patients who underwent surgery between January 2007 and December 2009 in our institution. The registered data were extracted from patient files and statistically analysed. These data included past medical history, clinical, laboratory and imaging data, duration of hospital stay and post operative complications. Patient delay (time between the appearance of symptoms and patient arrival at the emergency department) and hospital delay (time between hospital arrival and operation) were correctly investigated. Statistical analysis was done by using SPSS software. RESULTS: The patient delay is significantly increased in relation to the severity of appendicitis: 24 h (10.8-30.8 h) versus 37.4 h (36.8-38 h) (P < 0.05), unlike hospital delay, which remains constant (between simple and severe appendicitis): 7.5 h (5-14.8 h) versus 8 h (5-13 h). In severe appendicitis, the proportion of guarding, rebound tenderness, tachycardia (P < 0.05) and fever (P < 0.005) were significantly high, and leucocytosis (P < 0.05), C-reactive protein (CRP) (P < 0.001) and eosinopaenia [37.0 vs. 72.8 (P < 0.001)] were significantly different. Concerning computed tomography (CT) and echography, perforation, abscess formation (P < 0.05), phlegmon (P < 0.005) and peritonitis (P < 0.05) were significant signs of complicated cases. The length of hospital stay (P < 0.001) and duration of antibiotic therapy (P < 0.001) were statistically significant in cases of complicated appendicitis. CONCLUSION: Patient delay is a determining factor for the grade of appendicitis. It has an influence on the complications, length of hospital stay and duration of antibiotic treatment, unlike hospital delay. PMID- 26814551 TI - Prospective validation of the Ocular Trauma Score as a prognostic model to predict vision survival in injured adult patients from a developing country. AB - PURPOSE: To assess the prognostic value of the Ocular Trauma Score (OTS) in patients with eye injury treated in a University Hospital in South America. METHODS: One hundred and ninety subjects who were victims of eye trauma with different degrees of severity were evaluated and treated accordingly. Initial OTS categories were calculated for each patient and compared to the final visual result by transforming the achieved best-corrected visual acuity (BCVA) after treatment into OTS values. RESULTS: OTS visual acuity showed good correlation with the final BCVA after treatment [Spearman's rho = 0.857, 95 % confidence interval (CI) 0.813-0.891, P < 0.0001). No difference between the predicted BCVA and achieved BCVA was noticed (P < 0.0001, Chi-square test). CONCLUSION: The OTS provided useful information on outcomes treatment after eye trauma and can be used as a prognostic model to predict vision survival in injured adult patients from a developing country. PMID- 26814552 TI - The epidemiology of amputation injuries in the Austrian helicopter emergency medical service: a retrospective, nationwide cohort study. AB - PURPOSE: Data on the epidemiological characteristics of traumatic amputations in prehospital emergency care, especially in the context of air rescue, are scarce. Therefore, we aimed to describe the epidemiology of total and subtotal amputation injuries encountered by the OEAMTC helicopter emergency medical service (HEMS) in Austria, based on an almost nationwide sample. METHODS: We retrospectively reviewed all HEMS rescue missions flown for amputation injuries in 2009. Only primary missions were analyzed. RESULTS: In total, 149 out of 16,100 (0.9 %) primary HEMS rescue missions were for patients suffering from amputation injuries. Among these, HEMS physicians diagnosed 63.3 % (n = 94) total and 36.9 % (n = 55) subtotal amputations, with both groups showing a predominance of male victims (male:female ratios were 8:1 and 6:1, respectively).The highest rate occurred among adults between 45 and 64 years of age (35.6 %, n = 53). The most common causes were working with a circular saw (28.9 %, n = 43) and processing wood (16.8 %, n = 25). The majority of the cases included digital amputation injuries (77.2 %, n = 115) that were mainly related to the index finger (36.2 %, n = 54). One hundred forty patients (94.0 %) showed a total GCS of more than 12. Amputations were most prevalent in rural areas (84.6 %, n = 126) and between Thursday and Saturday (55.0 %, n = 82). The replantation rate after primary air transport was low (28 %). CONCLUSIONS: In the HEMS, amputation injuries are infrequent and mostly not life-threatening. However, HEMS crews need to maintain their focus on providing sufficient and fast primary care while facilitating rapid transport to a specialized hospital. The knowledge of the epidemiological characteristics of amputation injuries encountered in the HEMS gained in this study may be useful for educational and operational purposes. PMID- 26814553 TI - Shoulder outcome measures: is there a right answer? AB - PURPOSE: A number of outcome measures (instruments) are used to assess shoulder pain and function in clinical practice. No clear 'gold standard' exists and it is thought that different instruments will give a different answer. Our aim is to statistically compare four commonly used outcome measures in a group of trauma patients and to identify whether instruments which combine objective and subjective components differ from those which are purely subjective. METHODS: Forty-four patients undergoing internal fixation of proximal humeral fractures were recruited between 2003 and 2008. Each was asked to complete a number of outcome measures: University of Los Angeles score (UCLA); Constant and Murley score (Constant); Oxford Shoulder Score (OSS); Quick form of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH). Each were measured on a different scale but were standardised to 0-100 for comparison. RESULTS: Purely subjective instruments gave higher scores (better function and/or less pain). Statistical differences were found between each pair of instruments (p < 0.001), except for the comparison between UCLA and QuickDASH (p = 0.403). The study found inconsistencies between instruments, with outcomes varying depending on whether subjective or objective measurements were being assessed. CONCLUSIONS: Outcome measures are useful tools, but clinicians need to be aware that their choice of instrument should be made carefully, taking into account the reason behind its use with regard to outcome. PMID- 26814554 TI - Predictive ability of the ISS, NISS, and APACHE II score for SIRS and sepsis in polytrauma patients. AB - PURPOSE: Systemic inflammatory response syndrome (SIRS) and sepsis as causes of multiple organ dysfunction syndrome (MODS) remain challenging to treat in polytrauma patients. In this study, the focus was set on widely used scoring systems to assess their diagnostic quality. METHODS: A total of 512 patients (mean age: 39.2 +/- 16.2, range: 16-88 years) who had an Injury Severity Score (ISS) >=17 were included in this retrospective study. The patients were subdivided into four groups: no SIRS, slight SIRS, severe SIRS, and sepsis. The ISS, New Injury Severity Score (NISS), Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, and prothrombin time were collected at admission. The Kruskal-Wallis test and chi(2)-test, multinomial regression analysis, and kernel density estimates were performed. Receiver operating characteristic (ROC) analysis is reported as the area under the curve (AUC). Data were considered as significant if p < 0.05. RESULTS: All variables were significantly different in all groups (p < 0.001). The odds ratio increased with increasing SIRS severity for NISS (slight vs. no SIRS, 1.06, p = 0.07; severe vs. no SIRS, 1.07, p = 0.04; and sepsis vs. no SIRS, 1.11, p = 0.0028) and APACHE II score (slight vs. no SIRS, 0.97, p = 0.44; severe vs. no SIRS, 1.08, p = 0.02; and sepsis vs. no SIRS, 1.12, p = 0.0028). ROC analysis revealed that the NISS (slight vs. no SIRS, AUC 0.61; severe vs. no SIRS, AUC 0.67; and sepsis vs. no SIRS, AUC 0.77) and APACHE II score (slight vs. no SIRS, AUC 0.60; severe vs. no SIRS, AUC 0.74; and sepsis vs. no SIRS, AUC 0.82) had the best predictive ability for SIRS and sepsis. CONCLUSION: Quick assessment with the NISS or APACHE II score could preselect possible candidates for sepsis following polytrauma and provide guidance in trauma surgeons' decision-making. PMID- 26814555 TI - Fascia iliaca compartment block reduces morphine requirement pre-operatively for patients with fractured neck of femur. AB - INTRODUCTION: Fascia iliaca compartment block, performed in the emergency department (A&E) in patients presenting with femoral neck fracture, has gained increasing recognition as an adjunctive analgesic. The purpose of this study was to investigate whether fascia iliaca block (FIB) significantly reduced the requirement for systemic opiates in the pre-operative setting. MATERIALS AND METHODS: Analgesia requirements for all patients admitted with fractured neck of femur to one unit over a 9-month period were gathered prospectively. Fifty percent of patients had received FIB at diagnosis in the A&E, dependant on the expertise of the attending physician. Morphine administration between groups was analysed. RESULTS: Over a 9-month period, 286 patients with complete documentation were admitted with fractured neck of femur. At the start of the study, an informal education programme in A&E was introduced, increasing the incidence of FIB provision at diagnosis (p = <0.0001, Fisher's exact test) and reducing the average amount of morphine administered (p = 0.027, linear regression analysis). The administration of FIB reduced the average morphine requirement for a patient in A&E by 41 % when compared with those who received systemic analgesia alone (p = 0.018, Mann-Whitney test). No adverse effects were reported with FIB. CONCLUSION: Fascia iliaca compartment block is a safe and effective method of providing analgesia to patients with fractured neck of femur and reduces morphine requirement. PMID- 26814556 TI - ESTES News 5.12. PMID- 26814557 TI - Pre-contraction dynamic electrical impedance myography of the forearm finger flexors. AB - Electrical activity in the sensory-motor and supplementary motor areas of the cerebral cortex is known to occur during a 'readiness interval', extending up to 2 s before the relevant muscle actually contracts. This paper presents evidence that there are also changes in the properties of the muscle itself during a similar preparatory period, as revealed by dynamic electrical impedance myography. 11 healthy subjects aged 23.5 +/- 2.5 years were asked to perform a series of isometric gripping exercises during which the force, resistance and reactance of the forearm finger flexor muscles were monitored. A change in reactance, DeltaX, or resistance, DeltaR, which occurred before the generation of force, DeltaF, was dubbed a 'PIC', shorthand for precontraction impedance change (subject to criteria to rule out the possibility of simple 'noise'), of which 1206 qualified in the entire subject cohort. Such PIC's are statistically well correlated when expressed in terms of differences between PIC and force onset times (r ~ 0.9, p ~ 0). This is demonstrated using a variation on the 'computer of average transients' method. Precontraction impedance changes (PICs) occurring as much as 2 s before the onset of force generation were found, in qualitative agreement with precontraction EEG activity reported in the literature. Also, a subset of PIC's was found in which the scaled and time-shifted DeltaX(t) was virtually identical to DeltaF(t). Since the occurrence and timing of all the PICs depend on oral commands, it is clear that the auditory cortex is likely involved, but the detailed mechanism coupling brain activity with PICs is not known. PMID- 26814558 TI - Drastic Deprotonation Reactivity Difference of 3- and 5-Alkylpyrazole Isomers, Their I2-Catalyzed Thermal Isomerization, and Telescoping Synthesis of 3,5 Dialkylpyrazoles: The "Adjacent Lone Pair Effect" Demystified. AB - N-Protected 3-alkylpyrazoles are easily deprotonated by (n)BuLi at the 5-position of the aromatic ring, while the 5-alkyl isomers are completely unreactive under the same conditions. Using computational analysis, we reveal that electron pair repulsion within the deprotonated anion is not the reason behind the lack of reactivity of 5-alkylpyrazoles. Instead, diminished pi-resonance and attractive electrostatic interactions within the pyrazole ring are responsible for the observed effect. A greener, telescoping alternative to the synthesis of 3,5 dialkylpyrazoles is presented. PMID- 26814559 TI - Use of Bayesian Statistics for Pairwise Comparison of Megavariate Data Sets: Extracting Meaningful Differences between GCxGC-MS Chromatograms Using Jensen Shannon Divergence. AB - A new method for comparison of GCxGC-MS is proposed. The method is aimed at spotting the differences between two GCxGC-MS injections, in order to highlight the differences between two samples, in order to flag differences in composition, or to spot compounds only present in one of the samples. The method is based on application of the Jensen-Shannon divergence (JS) analysis combined with Bayesian hypothesis testing. In order to make the method robust against misalignment in both time dimensions, a moving-window approach is proposed. Using a Bayesian framework, we provide a probabilistic visual map (i.e., log likelihood ratio map) of the significant differences between two data sets consequently excluding the deterministic (i.e., "yes" or "no") decision. We proved this approach to be a versatile tool in GCxGC-MS data analysis, especially when the differences are embedded inside a complex matrix. We tested the approach to spot contamination of diesel samples. PMID- 26814560 TI - Superatom State-Resolved Dynamics of the Au25(SC8H9)18(-) Cluster from Two Dimensional Electronic Spectroscopy. AB - Superatom state-resolved dynamics of the Au25(SC8H9)18(-) monolayer-protected cluster (MPC) were examined using femtosecond two-dimensional electronic spectroscopy (2DES). The electronic ground state of the Au25(SC8H9)18(-) MPC is described by an eight-electron P-like superatom orbital. Hot electron relaxation (200 +/- 15 fs) within the superatom D manifold of lowest-unoccupied molecular orbitals was resolved from hot hole relaxation (290 +/- 20 fs) in the superatom P states by using 2DES in a partially collinear pump-probe geometry. Electronic relaxation dynamics mediated by specific superatom states were distinguished by examining the time-dependent cross-peak amplitudes for specific excitation and detection photon energy combinations. Quantification of the time-dependent amplitudes and energy positions of cross peaks in the 2.21/1.85 eV (excitation/detection) region confirmed that an apparent energetic blue shift observed for transient bleach signals results from rapid hot electron relaxation in the superatom D states. The combination of structurally precise MPCs and state resolved 2DES can be used to examine directly the influence of nanoscale structural modifications on electronic carrier dynamics, which are critical for developing nanocluster-based photonic devices. PMID- 26814561 TI - Multipurpose Polymeric Coating for Functionalizing Inert Polymer Surfaces. AB - In this work, we report on the development of a highly functionalizable polymer coating prepared by the chemical coupling of trichlorosilane (TCS) to the vinyl groups of poly(vinylmethyl siloxane) (PVMS). The resultant PVMS-TCS copolymer can be coated as a functional organic primer layer on a variety of polymeric substrates, ranging from hydrophilic to hydrophobic. Several case studies demonstrating the remarkable and versatile properties of PVMS-TCS coatings are presented. In particular, PVMS-TCS is found to serve as a convenient precursor for the deposition of organosilanes and the subsequent growth of polymer brushes, even on hydrophobic surfaces, such as poly(ethylene terephthalate) and polypropylene. In this study, the physical and chemical characteristics of these versatile PVMS-TCS coatings are interrogated by an arsenal of experimental probes, including scanning electron microscopy, water contact-angle measurements, ellipsometry, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and near-edge X-ray absorption fine structure spectroscopy. PMID- 26814562 TI - Interplay of Bias-Driven Charging and the Vibrational Stark Effect in Molecular Junctions. AB - We observe large, reversible, bias driven changes in the vibrational energies of PCBM based on simultaneous transport and surface-enhanced Raman spectroscopy (SERS) measurements on PCBM-gold junctions. A combination of linear and quadratic shifts in vibrational energies with voltage is analyzed and compared with similar measurements involving C60-gold junctions. A theoretical model based on density functional theory (DFT) calculations suggests that both a vibrational Stark effect and bias-induced charging of the junction contribute to the shifts in vibrational energies. In the PCBM case, a linear vibrational Stark effect is observed due to the permanent electric dipole moment of PCBM. The vibrational Stark shifts shown here for PCBM junctions are comparable to or larger than the charging effects that dominate in C60 junctions. PMID- 26814563 TI - Integration Of Two Personality Factor Systems. AB - Six major personality factors in inventory items have been developed through previous investigations in this series. These factors have been defined by analyzing total scores over groups of homogeneous items. An inventory containing items t o measure these factors, the Comrey inventory, and the Guilford Zimmerman Temperament Survey, or GZTS, were administered to 262 volunteers. The GZTS was divided up into groups of relatively homogeneous items. Total scores over 80 item groups from the two inventories were intercorrelated and factor analyzed. Of the 10 major factors obtained, three were represented only by item groups from the GZTS, namely, General Activity, Thoughtfulness, and Masculinity. Empathy and Compulsion were defined al- most exclusively by item groups from the Comrey inventory. The remaining major factors, Shyness, Dependence, Neuroticism, Hostility, and Socialization, were defined by item groups from both inventories. PMID- 26814564 TI - Simplex Components. AB - Simplex-like correlation matrices, reflecting the interrelationships among the stages of sequential behavior, are analyzed to determine the components underlying the simplex pattern. Several methods of analysis are employed to test whether a molar component or factor components can best account for the pattern. PMID- 26814565 TI - Figural Creativity, Intelligence, And Personality In Children. AB - To study relationships among figural creativity, intelligence, and personality, 30 measures hypothesized to be relevant were obtained for 196 children in grades 4, 5, and 6. Principal components extracted from the intercorrelations were rotated to the normalized varimax criterion. Nine factors were interpreted: A, chronological age and general information; B, personal adjustment; C, sex-typing; D, school achievement and mental ability; E, divergent production of figural implications; F, intolerance of ambiguity; G, production of figural systems; H, preference for complexity; and I, self-confidence. It was concluded that, even in children this young, separable orthogonal traits of figural divergent thinking could be delineated, and that "creativity" is not a unitary ability. PMID- 26814566 TI - Association Structures Of Bright Children At Ages Nine And Twelve. AB - The factor structure of free word associations of children, age 9 and 12, was the same as that for adults. Idiodynamic associative sets of 9-year-old children predicted their commonality scores, but not their reaction times. Both of these variables were predicted by the idiodynamic sets of 12-year-old children. It was speculated that idiodynamic associative sets reflect the organization (independent of culture) of the personal word "dictionary" evolved by children in preschool years, that a "common" (dependent upon culture) association hierarchy evolves independently of the "dictionary," and that variability in free word association dependent variables is a partial function of conflict between these two association hierarchies. PMID- 26814567 TI - Replication Of Symptom Distress Factors In Anxious Neurotic Outpatients. AB - In an attempt to replicate the factor structure of symptom distress re- ported by Mattsson et al. in their study of 404 anxious neurotic outpatients, the same 68 item pretreatment self-report Symptom Check List was administered to an independent but clinically similar sample of 1,116 patients. Using an identical factor-analytic procedure, five useful factors were extracted: Neurotic Feelings, Somatization, Performance Difficulty, Fear-Anxiety, and Depression. Four of these factors were almost identical to those reported by Mattsson e t al. while the fifth factor, Depression, seemed to represent a composite of the two small Depression factors (Anxious and Somatic) found in the earlier study. This minor discrepancy was discussed and the future research potential of these factors was indicated. PMID- 26814568 TI - Comparative Cluster Analysis Of Social Areas. AB - Three demographic dimensions previously isolated by cluster analysis procedures (using BC TRY System computer analyses) were compared in different metropolitan areas for their stability over time and place. Also, the social areas discovered within the communities were studied for their stability over time and place. The three demographic dimensions (socio-economic independence, family life, and assimilation) accounted for the generality of 33 census tract (1940) characteristics in two communities. It was also shown that the three basic dimensions were essentially unchanged during the decade which included World War 11. The stability of these dimensions was retained even though there was considerable change in residents in each metropolitan area during the decade. The validity of cluster-search procedures is demonstrated by the stability of the three demographic dimensions. PMID- 26814569 TI - Multidimensional Scaling Of N Sets Of Similarity Measures: A Nonmetric Individual Differences Approach. AB - Given N sets of similarity measures between pairs of stimulus objects a nonmetric multidimensional scaling procedure (known as CEMD) is proposed which allows one of four kinds of analysis to be performed on the data. The four types of solution are defined in terms of two binary decisions: (a) whether only one configuration is allowed for all N sets or whether each set is allowed to have its own configuration; and (b) whether the same mono- tonic transformation is applied to all N sets of input data or whether each set is allowed its own monotonic transformation. Where separate configurations are allowed the computer program seeks to keep these solutions as similar as possible and provides an index of the similarity of the configurations. PMID- 26814570 TI - Brief Report: Maxplane Meets Thurstone's "Factorially Invariant" Box Problem. AB - Using Maxplane, Thurstone's Box Problem is shown to be indeterminate. Slight modifications of the data matrix eventually allow an exactly perfect solution, however. It is suggested that obtained data matrices may often not be determinate with respect to simple structure, and that prolonged experimentation may be required before it is reasonable to expect such determinacy. I. PMID- 26814571 TI - Brief Report: An Additional Minimal Transformation To Orthonormality. PMID- 26814572 TI - Evaluation of Range-Corrected Density Functionals for the Simulation of Pyridinium-Containing Molecular Crystals. AB - The problem of nonlocal interactions in density functional theory calculations has in part been mitigated by the introduction of range-corrected functional methods. While promising solutions, the continued evaluation of range corrections in the structural simulations of complex molecular crystals is required to judge their efficacy in challenging chemical environments. Here, three pyridinium-based crystals, exhibiting a wide range of intramolecular and intermolecular interactions, are used as benchmark systems for gauging the accuracy of several range-corrected density functional techniques. The computational results are compared to low-temperature experimental single-crystal X-ray diffraction and terahertz spectroscopic measurements, enabling the direct assessment of range correction in the accurate simulation of the potential energy surface minima and curvatures. Ultimately, the simultaneous treatment of both short- and long-range effects by the omegaB97-X functional was found to be central to its rank as the top performer in reproducing the complex array of forces that occur in the studied pyridinium solids. These results demonstrate that while long-range corrections are the most commonly implemented range-dependent improvements to density functionals, short-range corrections are vital for the accurate reproduction of forces that rapidly diminish with distance, such as quadrupole quadrupole interactions. PMID- 26814573 TI - An epigenetic switch ensures transposon repression upon dynamic loss of DNA methylation in embryonic stem cells. AB - DNA methylation is extensively remodeled during mammalian gametogenesis and embryogenesis. Most transposons become hypomethylated, raising the question of their regulation in the absence of DNA methylation. To reproduce a rapid and extensive demethylation, we subjected mouse ES cells to chemically defined hypomethylating culture conditions. Surprisingly, we observed two phases of transposon regulation. After an initial burst of de-repression, various transposon families were efficiently re-silenced. This was accompanied by a reconfiguration of the repressive chromatin landscape: while H3K9me3 was stable, H3K9me2 globally disappeared and H3K27me3 accumulated at transposons. Interestingly, we observed that H3K9me3 and H3K27me3 occupy different transposon families or different territories within the same family, defining three functional categories of adaptive chromatin responses to DNA methylation loss. Our work highlights that H3K9me3 and, most importantly, polycomb-mediated H3K27me3 chromatin pathways can secure the control of a large spectrum of transposons in periods of intense DNA methylation change, ensuring longstanding genome stability. PMID- 26814574 TI - Maternally provided LSD1/KDM1A enables the maternal-to-zygotic transition and prevents defects that manifest postnatally. AB - Somatic cell nuclear transfer has established that the oocyte contains maternal factors with epigenetic reprogramming capacity. Yet the identity and function of these maternal factors during the gamete to embryo transition remains poorly understood. In C. elegans, LSD1/KDM1A enables this transition by removing H3K4me2 and preventing the transgenerational inheritance of transcription patterns. Here we show that loss of maternal LSD1/KDM1A in mice results in embryonic arrest at the 1-2 cell stage, with arrested embryos failing to undergo the maternal-to zygotic transition. This suggests that LSD1/KDM1A maternal reprogramming is conserved. Moreover, partial loss of maternal LSD1/KDM1A results in striking phenotypes weeks after fertilization; including perinatal lethality and abnormal behavior in surviving adults. These maternal effect hypomorphic phenotypes are associated with alterations in DNA methylation and expression at imprinted genes. These results establish a novel mammalian paradigm where defects in early epigenetic reprogramming can lead to defects that manifest later in development. PMID- 26814575 TI - Guanylate binding proteins directly attack Toxoplasma gondii via supramolecular complexes. AB - GBPs are essential for immunity against intracellular pathogens, especially for Toxoplasma gondii control. Here, the molecular interactions of murine GBPs (mGBP1/2/3/5/6), homo- and hetero-multimerization properties of mGBP2 and its function in parasite killing were investigated by mutational, Multiparameter Fluorescence Image Spectroscopy, and live cell microscopy methodologies. Control of T. gondii replication by mGBP2 requires GTP hydrolysis and isoprenylation thus, enabling reversible oligomerization in vesicle-like structures. mGBP2 undergoes structural transitions between monomeric, dimeric and oligomeric states visualized by quantitative FRET analysis. mGBPs reside in at least two discrete subcellular reservoirs and attack the parasitophorous vacuole membrane (PVM) as orchestrated, supramolecular complexes forming large, densely packed multimers comprising up to several thousand monomers. This dramatic mGBP enrichment results in the loss of PVM integrity, followed by a direct assault of mGBP2 upon the plasma membrane of the parasite. These discoveries provide vital dynamic and molecular perceptions into cell-autonomous immunity. PMID- 26814576 TI - New 4-Functionalized Glutamate Analogues Are Selective Agonists at Metabotropic Glutamate Receptor Subtype 2 or Selective Agonists at Metabotropic Glutamate Receptor Group III. AB - The metabotropic glutamate (Glu) receptors (mGluRs) play key roles in modulating excitatory neurotransmission in the brain. In all, eight subtypes have been identified and divided into three groups, group I (mGlu1,5), group II (mGlu2,3), and group III (mGlu4,6-8). In this article, we present a L-2,4-syn-substituted Glu analogue, 1d, which displays selective agonist activity at mGlu2 over the remaining mGluR subtypes. A modeling study and redesign of the core scaffold led to the stereoselective synthesis of four new conformationally restricted Glu analogues, 2a-d. Most interestingly, 2a retained a selective agonist activity profile at mGlu2 (EC50 in the micromolar range), whereas 2c/2d were both selective agonists at group III, subtypes mGlu4,6,8. In general, 2d was 20-fold more potent than 2c and potently activated mGlu4,6,8 in the low-mid nanomolar range. PMID- 26814577 TI - Multifrequency cw-EPR and DFT Studies of an Apparent Compressed Octahedral Cu(II) Complex. AB - The syntheses and single-crystal X-ray structures of the mononuclear complexes [Cu(bmet)](ClO4)2.H2O, [Cu(bmet)]Br2.2MeCN, and [Zn(bmet)](ClO4)2.H2O (bmet = N,N'-bis(2,2'-bipyridin-6-ylmethyl)ethane-1,2-diamine) are described. All three complexes feature a central metal ion bound to all six N atoms of the bmet ligand, which displays a meridional-facial-facial-meridional (mffm) configuration. The three complexes show one N-M-N axis to be significantly shorter than the others in agreement with an apparent compressed octahedral geometry. The X-ray structures of a single crystal of [Cu(bmet)](ClO4)2.0.375H2O resolved from data recorded at different temperatures display no remarkable structural modifications. However, they all display both as a powder and, in solution, an axial g1 > g2 ? g3 > g(e) electron paramagnetic resonance (EPR) pattern at low temperature, which is indicative of tetragonally elongated octahedra, while at room temperature the Q-band EPR spectra display a more rhombic g1 ? g2 > g3 > g(e) pattern. The fully density functional theory optimized structure of the Cu(II) complexes displays significant structural modifications only along one N(imine)-M-N(amine) axis resulting in an elongated octahedral structure. Furthermore, the EPR parameters predicted from this structure are comparable to those determined experimentally from the axial EPR signal recorded at low temperature, consistent with the unpaired electron residing mainly in the {3d(x(2)-y(2))} orbital. The structural and electronic properties of [Cu(bmet)](2+) are different from those in other previously described dynamic Jahn-Teller systems. We propose that these data can be rationalized by a dynamic Jahn-Teller effect perturbed by the strain of the hexadentate bmet ligand. PMID- 26814579 TI - A combined quantum-chemical and matrix-isolation study on molecular manganese fluorides. AB - Molecular manganese fluorides were studied using quantum-chemical calculations at DFT and CCSD(T) levels and experimentally by matrix-isolation techniques. They were prepared by co-deposition of IR-laser ablated elemental manganese or manganese trifluoride with F2 in an excess of Ne, Ar, or N2 or with neat F2 at 5 12 K. New IR bands in the Mn-F stretching region are detected and assigned to matrix-isolated molecular MnFx (x = 1-3). PMID- 26814581 TI - Single-crystalline aluminum film for ultraviolet plasmonic nanolasers. AB - Significant advances have been made in the development of plasmonic devices in the past decade. Plasmonic nanolasers, which display interesting properties, have come to play an important role in biomedicine, chemical sensors, information technology, and optical integrated circuits. However, nanoscale plasmonic devices, particularly those operating in the ultraviolet regime, are extremely sensitive to the metal and interface quality. Thus, these factors have a significant bearing on the development of ultraviolet plasmonic devices. Here, by addressing these material-related issues, we demonstrate a low-threshold, high characteristic-temperature metal-oxide-semiconductor ZnO nanolaser that operates at room temperature. The template for the ZnO nanowires consists of a flat single crystalline Al film grown by molecular beam epitaxy and an ultrasmooth Al2O3 spacer layer synthesized by atomic layer deposition. By effectively reducing the surface plasmon scattering and metal intrinsic absorption losses, the high quality metal film and the sharp interfaces formed between the layers boost the device performance. This work should pave the way for the use of ultraviolet plasmonic nanolasers and related devices in a wider range of applications. PMID- 26814582 TI - Gene coexpression modules in human cognition. PMID- 26814583 TI - Natural killers in the brain's nursery. PMID- 26814584 TI - Life goes by: a visual circuit signals perceptual-motor mismatch. PMID- 26814585 TI - Seq-ing the cortex one neuron at a time. PMID- 26814586 TI - Rapid control of olfaction. PMID- 26814587 TI - Astrocyte calcium signaling: the third wave. AB - The discovery that transient elevations of calcium concentration occur in astrocytes, and release 'gliotransmitters' which act on neurons and vascular smooth muscle, led to the idea that astrocytes are powerful regulators of neuronal spiking, synaptic plasticity and brain blood flow. These findings were challenged by a second wave of reports that astrocyte calcium transients did not mediate functions attributed to gliotransmitters and were too slow to generate blood flow increases. Remarkably, the tide has now turned again: the most important calcium transients occur in fine astrocyte processes not resolved in earlier studies, and new mechanisms have been discovered by which astrocyte [Ca(2+)]i is raised and exerts its effects. Here we review how this third wave of discoveries has changed our understanding of astrocyte calcium signaling and its consequences for neuronal function. PMID- 26814588 TI - Remodeling myelination: implications for mechanisms of neural plasticity. AB - One of the most significant paradigm shifts in membrane remodeling is the emerging view that membrane transformation is not exclusively controlled by cytoskeletal rearrangement, but also by biophysical constraints, adhesive forces, membrane curvature and compaction. One of the most exquisite examples of membrane remodeling is myelination. The advent of myelin was instrumental in advancing the nervous system during vertebrate evolution. With more rapid and efficient communication between neurons, faster and more complex computations could be performed in a given time and space. Our knowledge of how myelin-forming oligodendrocytes select and wrap axons has been limited by insufficient spatial and temporal resolution. By virtue of recent technological advances, progress has clarified longstanding controversies in the field. Here we review insights into myelination, from target selection to axon wrapping and membrane compaction, and discuss how understanding these processes has unexpectedly opened new avenues of insight into myelination-centered mechanisms of neural plasticity. PMID- 26814591 TI - Rhodium-catalyzed asymmetric ring opening reaction of oxabenzonorbornadienes with amines using ZnI2 as the activator. AB - The complex of [Rh(COD)Cl]2 and (R,R)-BDPP was used as an effective catalyst for the asymmetric ring opening reaction of oxabenzonorbornadienes with various amines by employing ZnI2 as the activator. Under the optimized reaction conditions, high enantioselectivities with good yields could be obtained from a wide scope of oxabenzonorbornadienes and amines. PMID- 26814592 TI - Geometrically confined ultrasmall gadolinium oxide nanoparticles boost the T(1) contrast ability. AB - High-performance magnetic resonance imaging (MRI) contrast agents and novel contrast enhancement strategies are urgently needed for sensitive and accurate diagnosis. Here we report a strategy to construct a new T1 contrast agent based on the Solomon-Bloembergen-Morgan (SBM) theory. We loaded the ultrasmall gadolinium oxide nanoparticles into worm-like interior channels of mesoporous silica nanospheres (Gd2O3@MSN nanocomposites). This unique structure endows the nanocomposites with geometrical confinement, high molecular tumbling time, and a large coordinated number of water molecules, which results in a significant enhancement of the T1 contrast with longitudinal proton relaxivity (r1) as high as 45.08 mM(-1) s(-1). Such a high r1 value of Gd2O3@MSN, compared to those of ultrasmall Gd2O3 nanoparticles and gadolinium-based clinical contrast agents, is mainly attributed to the strong geometrical confinement effect. This strategy provides new guidance for developing various high-performance T1 contrast agents for sensitive imaging and disease diagnosis. PMID- 26814589 TI - Lateral hypothalamic circuits for feeding and reward. AB - In experiments conducted over 60 years ago, the lateral hypothalamic area (LHA) was identified as a critical neuroanatomical substrate for motivated behavior. Electrical stimulation of the LHA induces voracious feeding even in well-fed animals. In the absence of food, animals will work tirelessly, often lever pressing thousands of times per hour, for electrical stimulation at the same site that provokes feeding, drinking and other species-typical motivated behaviors. Here we review the classic findings from electrical stimulation studies and integrate them with more recent work that has used contemporary circuit-based approaches to study the LHA. We identify specific anatomically and molecularly defined LHA elements that integrate diverse information arising from cortical, extended amygdala and basal forebrain networks to ultimately generate a highly specified and invigorated behavioral state conveyed via LHA projections to downstream reward and feeding-specific circuits. PMID- 26814593 TI - Speciation, Ecological Opportunity, and Latitude (American Society of Naturalists Address). AB - Evolutionary hypotheses to explain the greater numbers of species in the tropics than the temperate zone include greater age and area, higher temperature and metabolic rates, and greater ecological opportunity. These ideas make contrasting predictions about the relationship between speciation processes and latitude, which I elaborate and evaluate. Available data suggest that per capita speciation rates are currently highest in the temperate zone and that diversification rates (speciation minus extinction) are similar between latitudes. In contrast, clades whose oldest analyzed dates precede the Eocene thermal maximum, when the extent of the tropics was much greater than today, tend to show highest speciation and diversification rates in the tropics. These findings are consistent with age and area, which is alone among hypotheses in predicting a time trend. Higher recent speciation rates in the temperate zone than the tropics suggest an additional response to high ecological opportunity associated with low species diversity. These broad patterns are compelling but provide limited insights into underlying mechanisms, arguing that studies of speciation processes along the latitudinal gradient will be vital. Using threespine stickleback in depauperate northern lakes as an example, I show how high ecological opportunity can lead to rapid speciation. The results support a role for ecological opportunity in speciation, but its importance in the evolution of the latitudinal gradient remains uncertain. I conclude that per capita evolutionary rates are no longer higher in the tropics than the temperate zone. Nevertheless, the vast numbers of species that have already accumulated in the tropics ensure that total rate of species production remains highest there. Thus, tropical evolutionary momentum helps to perpetuate the steep latitudinal biodiversity gradient. PMID- 26814590 TI - Melanocortin-4 receptor-regulated energy homeostasis. AB - The melanocortin system provides a conceptual blueprint for the central control of energetic state. Defined by four principal molecular components--two antagonistically acting ligands and two cognate receptors--this phylogenetically conserved system serves as a prototype for hierarchical energy balance regulation. Over the last decade the application of conditional genetic techniques has facilitated the neuroanatomical dissection of the melanocortinergic network and identified the specific neural substrates and circuits that underscore the regulation of feeding behavior, energy expenditure, glucose homeostasis and autonomic outflow. In this regard, the melanocortin-4 receptor is a critical coordinator of mammalian energy homeostasis and body weight. Drawing on recent advances in neuroscience and genetic technologies, we consider the structure and function of the melanocortin-4 receptor circuitry and its role in energy homeostasis. PMID- 26814594 TI - Chemical cytometry of thiols using capillary zone electrophoresis-laser induced fluorescence and TMPAB-o-M, an improved fluorogenic reagent. AB - Low molecular weight thiol compounds play crucial roles in many physiological processes. Most methods for determination of thiol compounds are population averaged; few methods for quantification of thiol compounds in single cells have been reported. We report an ultrasensitive method for determination of thiol compounds in single cells by use of 1,3,5,7-tetramethyl-8-phenyl-(2-maleimide) difluoroboradiaza-s-indacene (TMPAB-o-M), a fluorogenic probe with useful spectral properties, coupled with capillary zone electrophoresis and laser induced fluorescence detection using a post-column sheath flow cuvette. TMPAB-o-M provides low background, high sensitivity, and excellent reactivity. After optimization of the separation method, we achieved baseline separation of labeled glutathione (GSH), cysteine (Cys), homocysteine, and gamma-glutamylcysteine within 11 min, and produced concentration limits of detection from 10 to 20 pM and mass LODs of 65 to 100 zmol. The method was applied for analysis of thiol containing compounds in both cell homogenates and in single HCT-29 and MCF-10A cells. GSH was the main thiol, and Cys was also detected in both cell types. Cells were treated with N-ethylmaleimide, which significantly attenuated thiol levels. PMID- 26814596 TI - Another Scale for the Assessment of Facial Paralysis? ADS Scale: Our Proposition, How to Use It. AB - INTRODUCTION: Several authors in the years propose different methods to evaluate areas and specific movement's disease in patient affected by facial palsy. Despite these efforts the House Brackmann is anyway the most used assessment in medical community. AIM: The aims of our study is the proposition and assessing a new rating Arianna Disease Scale (ADS) for the clinical evaluation of facial paralysis. MATERIALS AND METHODS: Sixty patients affected by unilateral facial Bell paralysis were enrolled in a prospective study from 2012 to 2014. Their facial nerve function was evaluated with our assessment analysing facial district divided in upper, middle and lower third. We analysed different facial expressions. Each movement corresponded to the action of different muscles. The action of each muscle was scored from 0 to 1, with 0 corresponding from complete flaccid paralysis to muscle's normal function ending with a score of 1. Synkinesis was considered and evaluated also in the scale with a fixed 0.5 score. Our results considered ease and speed of evaluation of the assessment, the accuracy of muscle deficit and the ability to calculate synkinesis using a score. RESULTS: All the three observers agreed 100% in the highest degree of deficit. We found some discrepancies in intermediate score with 92% agreement in upper face, 87% in middle and 80% in lower face, where there were more muscles involved in movements. CONCLUSION: Our scale had some limitations linked to the small group of patients evaluated and we had a little difficulty understanding the intermediate score of 0.3 and 0.7. However, this was an accurate tool to quickly evaluate facial nerve function. This has potential as an alternative scale to and to diagnose facial nerve disorders. PMID- 26814595 TI - Association of the solute carrier family 11 member 1 gene polymorphisms with susceptibility to leprosy in a Brazilian sample. AB - Natural resistance-associated macrophage protein 1/solute carrier family 11 member 1 gene (Nramp1/Slc11a1) is a gene that controls the susceptibility of inbred mice to intracellular pathogens. Polymorphisms in the human Slc11a1/Nramp1 gene have been associated with host susceptibility to leprosy. This study has evaluated nine polymorphisms of the Slc11a1/Nramp1 gene [(GT)n, 274C/T, 469+14G/C, 577-18G/A, 823C/T, 1029 C/T, 1465-85G/A, 1703G/A, and 1729+55del4] in 86 leprosy patients (67 and 19 patients had the multibacillary and the paucibacillary clinical forms of the disease, respectively), and 239 healthy controls matched by age, gender, and ethnicity. The frequency of allele 2 of the (GT)n polymorphism was higher in leprosy patients [p = 0.04, odds ratio (OR) = 1.49], whereas the frequency of allele 3 was higher in the control group (p = 0.03; OR = 0.66). Patients carrying the 274T allele (p = 0.04; OR = 1.49) and TT homozygosis (p = 0.02; OR = 2.46), such as the 469+14C allele (p = 0.03; OR = 1.53) of the 274C/T and 469+14G/C polymorphisms, respectively, were more frequent in the leprosy group. The leprosy and control groups had similar frequency of the 577-18G/A, 823C/T, 1029C/T, 1465-85G/A, 1703G/A, and 1729+55del4 polymorphisms. The 274C/T polymorphism in exon 3 and the 469+14G/C polymorphism in intron 4 were associated with susceptibility to leprosy, while the allele 2 and 3 of the (GT)n polymorphism in the promoter region were associated with susceptibility and protection to leprosy, respectively. PMID- 26814597 TI - Presystolic A wave may predict increased arterial stiffness in asymptomatic individuals. AB - BACKGROUND: Stiffness of large arteries has been related to cardiovascular mortality. The cardioankle vascular index (CAVI) is a novel parameter of arterial stiffness. The main aim of the present study was to investigate the association between presystolic wave (PSW) on left ventricular outflow tract (LVOT) and CAVI. PATIENTS AND METHODS: Patients admitted to the cardiology outpatient clinic were consecutively enrolled. Arterial stiffness was assessed by the CAVI. It was measured using a VaSera VS-1000 CAVI instrument. Pulse Doppler flow evaluation in LVOT was performed just proximal to the aortic valve in an apical five-chamber view. The presence of a PSW preceding the LVOT flow was assessed in all patients. RESULTS: A total of 200 patients were enrolled consecutively. Patients with PSW had higher CAVI values compared with those without PSW (8.6+/-1.6 vs. 7.3+/-1.5). There was a significant correlation between PSW velocity and CAVI (r=0.34, P<0.001). Analysis using the receiver operating characteristics curve showed that PSW velocity of 61 cm/s constitutes the cutoff value for abnormal CAVI (CAVI>=9) with 75% sensitivity and 74% specificity (area under the curve: 0.883, 95% confidence interval: 0.694-0.972). CONCLUSION: Assessment of presystolic A wave on echocardiography examination may provide important information on the vascular function, which has a prognostic impact. PMID- 26814598 TI - Recent Advances on Mass Spectrometry Analysis of Nitrated Phospholipids. AB - In recent years, there has been an increasing interest in nitro fatty acids (NO2 FA) as signaling molecules formed under nitroxidative stress. NO2-FA were detected in vivo in a free form, although it is assumed that they may also be esterified to phospholipids (PL). Nevertheless, insufficient discussion about the nature, origin, or role of nitro phospholipids (NO2-PL) was reported up to now. The aim of this study was to develop a mass spectrometry (MS) based approach which allows identifying nitroalkenes derivatives of three major PL classes found in living systems: phosphatidylcholines (PCs), phosphatidylethanolamine (PEs), and phosphatidylserines (PSs). NO2-PLs were generated by NO2BF4 in hydrophobic environment, mimicking biological systems. The NO2-PLs were then detected by electrospray ionization (ESI-MS) and ESI-MS coupled to hydrophilic interaction liquid chromatography (HILIC). Identified NO2-PLs were further analyzed by tandem MS in positive (as [M + H](+) ions for all PL classes) and negative-ion mode (as [M - H](-) ions for PEs and PSs and [M + OAc](-) ions for PCs). Typical MS/MS fragmentation pattern of all NO2-PL included a neutral loss of HNO2, product ions arising from the combined loss of polar headgroup and HNO2, [NO2-FA + H](+) and [NO2-FA - H](-) product ions, and cleavages on the fatty acid backbone near the nitro group, allowing its localization within the FA akyl chain. Developed MS method was used to identify NO2-PL in cardiac mitochondria from a well characterized animal model of type 1 diabetes mellitus. We identified nine NO2 PCs and one NO2-PE species. The physiological relevance of these findings is still unknown. PMID- 26814599 TI - Subcomponent Flexibility Enables Conversion between D4-Symmetric Cd(II)8L8 and T Symmetric Cd(II)4L4 Assemblies. AB - A flexible tris-formylpyridine subcomponent A was observed to produce three distinct products following Cd(II)-templated self-assembly with different anilines. Two of the products were Cd(II)4L4 tetrahedra, one with ligands puckered inward, and the other outward. The third product was a Cd(II)8L8 structure having all mer stereochemistry, contrasting with the fac stereochemistry of the tetrahedra. These three complexes were observed to coexist in solution. The equilibrium between them could be influenced through guest binding and specific interactions between aniline subcomponents, allowing a selected one of the three to predominate under defined conditions. PMID- 26814600 TI - Supramolecular Organic Nanowires as Plasmonic Interconnects. AB - Metallic nanostructures are able to interact with an incident electromagnetic field at subwavelength scales by plasmon resonance which involves the collective oscillation of conduction electrons localized at their surfaces. Among several possible applications of this phenomenon, the theoretical prediction is that optical circuits connecting multiple plasmonic elements will surpass classical electronic circuits at nanoscale because of their much faster light-based information processing. However, the placement and coupling of metallic elements smaller than optical wavelengths currently remain a formidable challenge by top down manipulations. Here, we show that organic supramolecular triarylamine nanowires of ~1 nm in diameter are able to act as plasmonic waveguides. Their self-assembly into plasmonic interconnects between arrays of gold nanoparticles leads to the bottom-up construction of basic optical nanocircuits. When the resonance modes of these metallic nanoparticles are coupled through the organic nanowires, the optical conductivity of the plasmonic layer dramatically increases from 259 to 4271 Omega(-1).cm(-1). We explain this effect by the coupling of a hot electron/hole pair in the nanoparticle antenna with the half-filled polaronic band of the organic nanowire. We also demonstrate that the whole hybrid system can be described by using the abstraction of the lumped circuit theory, with a far field optical response which depends on the number of interconnects. Overall, our supramolecular bottom-up approach opens the possibility to implement processable, soft, and low cost organic plasmonic interconnects into a large number of applications going from sensing to metamaterials and information technologies. PMID- 26814602 TI - A Unified Latent Curve, Latent State-Trait Analysis of the Developmental Trajectories and Correlates of Positive Orientation. AB - Literature documents that the judgments people hold about themselves, their life, and their future are important ingredients of their psychological functioning and well-being and are commonly related to each other. In this article, results from a longitudinal study (N = 298, 45% males) are presented. Using an integrative Latent Curve, Latent State-Trait Model ( Tisak & Tisak, 2000 ), results corroborated (a) the impressive mean level and rank-order stability of positive orientation across a 4-year period, (b) the traitlike nature of positive orientation, and (c) the strong association of positive orientation with intrapersonal (i.e., quality of daily emotional experiences) and interpersonal (i.e., quality of friendships) adolescents' areas of functioning and on psychological resilience. These results attest to the utility of the new construct as a critical component of individuals' optimal well-functioning. PMID- 26814601 TI - Direct-Write X-ray Nanopatterning: A Proof of Concept Josephson Device on Bi2Sr2CaCu2O8+delta Superconducting Oxide. AB - We describe the first use of a novel photoresist-free X-ray nanopatterning technique to fabricate an electronic device. We have produced a proof-of-concept device consisting of a few Josephson junctions by irradiating microcrystals of the Bi2Sr2CaCu2O8+delta (Bi-2212) superconducting oxide with a 17.6 keV synchrotron nanobeam. Fully functional devices have been obtained by locally turning the material into a nonsuperconducting state by means of hard X-ray exposure. Nano-XRD patterns reveal that the crystallinity is substantially preserved in the irradiated areas that there is no evidence of macroscopic crystal disruption. Indications are that O ions have been removed from the crystals, which could make this technique interesting also for other oxide materials. Direct-write X-ray nanopatterning represents a promising fabrication method exploiting material/material rather than vacuum/material interfaces, with the potential for nanometric resolution, improved mechanical stability, enhanced depth of patterning, and absence of chemical contamination with respect to traditional lithographic techniques. PMID- 26814603 TI - Augmenting Data With Published Results in Bayesian Linear Regression. AB - In most research, linear regression analyses are performed without taking into account published results (i.e., reported summary statistics) of similar previous studies. Although the prior density in Bayesian linear regression could accommodate such prior knowledge, formal models for doing so are absent from the literature. The goal of this article is therefore to develop a Bayesian model in which a linear regression analysis on current data is augmented with the reported regression coefficients (and standard errors) of previous studies. Two versions of this model are presented. The first version incorporates previous studies through the prior density and is applicable when the current and all previous studies are exchangeable. The second version models all studies in a hierarchical structure and is applicable when studies are not exchangeable. Both versions of the model are assessed using simulation studies. Performance for each in estimating the regression coefficients is consistently superior to using current data alone and is close to that of an equivalent model that uses the data from previous studies rather than reported regression coefficients. Overall the results show that augmenting data with results from previous studies is viable and yields significant improvements in the parameter estimation. PMID- 26814604 TI - The Impact of Covariates on Statistical Power in Cluster Randomized Designs: Which Level Matters More? AB - Field experiments with nested structures are becoming increasingly common, especially designs that assign randomly entire clusters such as schools to a treatment and a control group. In such large-scale cluster randomized studies the challenge is to obtain sufficient power of the test of the treatment effect. The objective is to maximize power without adding many clusters that make the study much more expensive. In this article I discuss how power estimates of tests of treatment effects in balanced cluster randomized designs are affected by covariates at different levels. I use third-grade data from Project STAR, a field experiment about class size, to demonstrate how covariates that explain a considerable proportion of variance in outcomes increase power significantly. When lower level covariates are group-mean centered and clustering effects are larger, top-level covariates increase power more than lower level covariates. In contrast, when clustering effects are smaller and lower level covariates are grand-mean centered or uncentered, lower level covariates increase power more than top-level covariates. PMID- 26814605 TI - Estimating the Reliability of Aggregated and Within-Person Centered Scores in Ecological Momentary Assessment. AB - A procedure for estimating the reliability of test scores in the context of ecological momentary assessment (EMA) was proposed to take into account the characteristics of EMA measures. Two commonly used test scores in EMA were considered: the aggregated score (AGGS) and the within-person centered score (WPCS). Conceptually, AGGS and WPCS represent the interindividual differences and the intraindividual differences, respectively. The reliability coefficients for AGGS and WPCS were derived using a multilevel factor model with a serial correlation structure framework. Point estimates and confidence intervals of these coefficients were obtained using Mx ( Neale, Boker, Xie, & Maes, 2004 ). A simulation study showed that the proposed procedure performed well empirically. Diary data from Huang (2009) , which recorded daily joy level of 110 undergraduate students for 8 days, was used to illustrate the applicability of the proposed method. PMID- 26814606 TI - Principal Cluster Axes: A Projection Pursuit Index for the Preservation of Cluster Structures in the Presence of Data Reduction. AB - A measure of "clusterability" serves as the basis of a new methodology designed to preserve cluster structure in a reduced dimensional space. Similar to principal component analysis, which finds the direction of maximal variance in multivariate space, principal cluster axes find the direction of maximum clusterability in multivariate space. Furthermore, the principal clustering approach falls into the class of projection pursuit techniques. Comparisons are made with existing methodologies both in a simulation study and analysis of real world data sets. Furthermore, a demonstration of how to interpret the results of the principal cluster axes is provided on the analysis of Supreme Court voting data and similarities between the interpretation of competing procedures (e.g., factor analysis and principal component analysis) are provided. In addition to the Supreme Court analysis, we analyze several data sets often used to test cluster analysis procedures, including Fisher's Iris data, Agresti's Crab data, and a data set on glass fragments. Finally, discussion is provided to help determine when the proposed procedure will be the most beneficial to the researcher. PMID- 26814607 TI - Controlling Chemical Reactions by Short, Intense Mid-Infrared Laser Pulses: Comparison of Linear and Circularly Polarized Light in Simulations of ClCHO(+) Fragmentation. AB - Enhanced mode selective fragmentation of oriented ClCHO(+) -> Cl + HCO(+), H + ClCO(+), HCl(+) + CO with linear polarized intense mid-IR pulses was demonstrated in our previous computational study ( J. Phys. Chem. Lett. 2012 , 3 , 2541 ). Simulations of angle-dependent strong field ionization of ClCHO indicate the ionization rate in the molecular plane is nearly twice as large as perpendicular to the plane, suggesting a degree of planar alignment can be obtained experimentally for ClCHO(+), starting from neutral molecules. Classical trajectory calculations with a 4 cycle 7 MUm laser pulse (peak intensity of 1.26 * 10(14) W/cm(2)) show that circularly polarized light with the electric field in the plane of the molecule deposits more energy and yields larger branching ratios for higher energy fragmentation channels than linearly polarized light with the same maximum field strength. These results suggest circularly polarized mid-IR pulses can not only achieve control on reactions but also provide an experimentally accessible implementation. PMID- 26814608 TI - The Merits of Malaria Diagnostics during an Ebola Virus Disease Outbreak. AB - Malaria is a major public health concern in the countries affected by the Ebola virus disease epidemic in West Africa. We determined the feasibility of using molecular malaria diagnostics during an Ebola virus disease outbreak and report the incidence of Plasmodium spp. parasitemia in persons with suspected Ebola virus infection. PMID- 26814609 TI - Oncolytic vaccinia virus as a vector for therapeutic sodium iodide symporter gene therapy in prostate cancer. AB - Oncolytic strains of vaccinia virus are currently in clinical development with clear evidence of safety and promising signs of efficacy. Addition of therapeutic genes to the viral genome may increase the therapeutic efficacy of vaccinia. We evaluated the therapeutic potential of vaccinia virus expressing the sodium iodide symporter (NIS) in prostate cancer models, combining oncolysis, external beam radiotherapy and NIS-mediated radioiodide therapy. The NIS-expressing vaccinia virus (VV-NIS), GLV-1h153, was tested in in vitro analyzes of viral cell killing, combination with radiotherapy, NIS expression, cellular radioiodide uptake and apoptotic cell death in PC3, DU145, LNCaP and WPMY-1 human prostate cell lines. In vivo experiments were carried out in PC3 xenografts in CD1 nude mice to assess NIS expression and tumor radioiodide uptake. In addition, the therapeutic benefit of radioiodide treatment in combination with viral oncolysis and external beam radiotherapy was measured. In vitro viral cell killing of prostate cancers was dose- and time-dependent and was through apoptotic mechanisms. Importantly, combined virus therapy and iodizing radiation did not adversely affect oncolysis. NIS gene expression in infected cells was functional and mediated uptake of radioiodide both in vitro and in vivo. Therapy experiments with both xenograft and immunocompetent Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mouse models showed that the addition of radioiodide to VV-NIS infected tumors was more effective than each single-agent therapy, restricting tumor growth and increasing survival. In conclusion, VV-NIS is effective in prostate cancer models. This treatment modality would be an attractive complement to existing clinical radiotherapy practice. PMID- 26814610 TI - Photodynamic Therapy Plus Chemotherapy Compared with Photodynamic Therapy Alone in Hilar Nonresectable Cholangiocarcinoma. AB - BACKGROUND/AIMS: Standard treatments are not available for hilar nonresectable cholangiocarcinoma (NCC). It is unknown whether combination therapy of photodynamic therapy (PDT) plus systemic chemotherapy is superior to PDT alone. METHODS: We retrospectively reviewed 68 patients with hilar NCC treated with either PDT plus chemotherapy (PTD-C) or PDT monotherapy (PDT-M). The primary endpoint was the mean overall survival rate. Secondary endpoints included the 1 year survival rate, risk of cholangitic complications, and outcomes, which were evaluated according to the chemotherapy protocol. RESULTS: More than 90% of the study population had advanced hilar NCC Bismuth type III or IV. In the PDT-M group (n=35), the mean survival time was 374 days compared with 520 days in the PDT-C group (n=33, p=0.021). The 1-year survival rate was significantly higher in the PDT-C group compared with the PDT-M group (88% vs 58%, p=0.001) with a significant reduction of mortality (hazard ratio, 0.20; 95% confidence interval, 0.07 to 0.58; p=0.003). Gemcitabine monotherapy resulted in a shorter survival time compared with the gemcitabine combination therapy (mean, 395 days vs 566 days; p=0.09). Cholangitic complications were observed at a similar frequency in the PDT-C and PDT-M groups. CONCLUSIONS: Combining repeated PDT with a gemcitabine-based combination therapy might offer a significant survival benefit in patients with hilar NCC. PMID- 26814611 TI - Newly Identified BRAF Mutation in Rheumatoid Arthritis. AB - OBJECTIVE: Rheumatoid arthritis (RA)-associated autoantibodies include those directed at the kinase site of BRAF (v-Raf murine sarcoma viral oncogene homolog B1), a serine-threonine kinase involved in the MAPK signaling pathway. To understand anti-BRAF immunization, we sought to identify BRAF mutations in the peripheral blood lymphocytes (PBLs) of patients with RA. METHODS: We first cloned the major BRAF region known for mutations in the pCR2.1 vector, using genomic DNA from the PBLs of 8 RA patients. For each patient, 100 clones were sequenced. In 5 of 8 patients, we detected a new BRAF mutation in 1 clone. The frequency of this new mutation was evaluated by droplet digital polymerase chain reaction in PBLs from RA patients and controls. To test whether p.Val600Ala influences the kinase activity of BRAF, we developed an in vitro assay based on phosphorylation of MEK 1, a major BRAF substrate. RESULTS: A BRAF mutation, p.Val600Ala, was identified in 1 of 8,000 PBLs and 1 of 6,000 T lymphocytes from RA patients and in 1 of 12,500 PBLs and 1 of 12,500 T lymphocytes from controls. The BRAF p.Val600Ala mutation was not correlated with the presence of anti-BRAF autoantibodies. The p.Val600Ala mutation activated phosphorylation of MEK-1 in vitro. CONCLUSION: Most RA patients have a p.Val600Ala mutation in the BRAF gene. This mutation activates the kinase activity of BRAF. The p.Val600Ala mutation could activate the MAPK pathway, leading to the activation of T lymphocytes. PMID- 26814612 TI - Isoflavone Profiles and Kinetic Changes during Ultra-High Temperature Processing of Soymilk. AB - Isoflavone profile is greatly affected by heating process. However, kinetic analyses of isoflavone conversion and degradation using a continuous industry processing method have never been characterized. In this study, Proto soybean was soaked and blanched at 80 degrees C for 2 min and then processed into soymilk, which underwent UHT (ultra-high temperature) at 135 to 150 degrees C for 10 to 50 s with a pilot plant-scale Microthermics processor. The isoflavone profile was determined at different time/temperature combinations. The results showed that all isoflavone forms exhibited distinct changing patterns over time. In the soymilk under UHT conditions, the degradation (disappearance) of malonyldaizin and malonylgenistin exhibited first-order kinetics with activation energies of 59 and 84 kj/mole, respectively. At all UHT temperatures, malonylgenistin showed higher rate constants than malonyldaidzin. However, malonylglycitin changed irregularly under these UHT temperatures. The increase of genistin, daidzin, glycitein and acetlydaidzin during heating demonstrated zero-order kinetics and the rate constants increased with temperature except for the conditions of 145 to 150 degrees C for 50 s. Overall, genistein series exhibited higher stability than daidzein series. Under all UHT conditions, total isoflavone decreased from 12% to 24%. PMID- 26814613 TI - Microfluidic-based non-enzymatic glycation enhances cross-linking of human scleral tissue compared to conventional soaking. AB - We evaluated nano-structural and chemical changes in human scleral collagen caused by non-enzymatic glycation using AFM, Raman spectroscopy, and microfluidics. Twenty 8 * 2 mm2 scleral strips (n = 5, each) were divided into four groups of pure sclera tissues (control group) and sclera tissues with incubation (1 hr in BSS and ribose) and preservation (23 hr in 90% ethanol) for 7 days (BSS + DR7 group) and 30 days (BSS + DR30 group) at room temperature, and 7 days in a microfluidic chip (BSS + DR + uF7 group). The BSS + DR7 and BSS + DR30 groups were incubated in a mixture of balanced salt solution (BSS) and 0.2 M D ribose in PBS, pH 7.4 containing 0.1% sodium azide, while the BSS + DR + uF7 group was incubated in the same solutions supplied by two inlet reservoirs from a microfluidic chip. The scleral tissues incubated in the microfluidic environment showed a clear irregular parallel arrangement of collagen fibrils with tangled fibrils. A Raman shift was observed at 919 cm-1 in the glycation groups. Non enzymatic glycation led to an increased in the density of scleral stromal collagen. Our method using non-enzymatic glycation in a microfluidic environment successfully induced collagen cross-linking. These in vitro results suggested that glycation can be used to strengthen connective tissues. SCANNING 38:421-426, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26814614 TI - Excess Mortality Due to Respiratory Causes in Patients With Rheumatoid Arthritis Should be Interpreted in the Context of "Never" or "Ever" Smoking and May be Due to Interstitial Lung Disease: Comment on the Article by Sparks et al. PMID- 26814616 TI - Histone Demethylation and Toll-like Receptor 8-Dependent Cross-Talk in Monocytes Promotes Transdifferentiation of Fibroblasts in Systemic Sclerosis Via Fra-2. AB - OBJECTIVE: To investigate whether epigenetic changes can modulate monocytes to produce tissue inhibitor of metalloproteinases 1 (TIMP-1) via Fra-2 (an activator protein 1 [AP-1] family member), a novel downstream mediator that promotes fibrogenesis. METHODS: AP-1 transcription factors and TIMP-1 expression were measured in monocytes from systemic sclerosis (SSc) patients and healthy controls. Involvement of Fra-2 in the regulation of TIMP-1 following treatment with Toll-like receptor 8 (TLR-8) agonist was investigated using a luciferase activity assay and chromatin immunoprecipitation (ChIP) analysis. Expression of TIMP-1 and Fra-2 was determined in response to TLR-8 treatment and to different histone modifications, including 3'-deazaneplanocin (DZNep) and apicidin. Fibroblasts from healthy controls were cocultured with DZNep plus TLR-8-treated healthy control monocytes. RESULTS: Up-regulation of Fra-2 was detected in bleomycin-challenged mice and in skin biopsy samples from SSc patients. Enhanced expression of Fra-2 and TIMP-1 was correlated in SSc monocytes (P = 0.021). The expression of Fra-1 was significantly reduced (P = 0.037) in SSc monocytes. Inhibiting AP-1 activity reduced TIMP-1 production in TLR-8-stimulated monocytes from healthy controls and SSc patients. ChIP experiments revealed binding of Fra 2 to the TIMP-1 promoter. Stimulation with DZNep plus TLR-8 enhanced Fra-2 and TIMP-1 expression in healthy control monocytes, whereas TLR-8 plus apicidin repressed Fra-2 and TIMP-1 expression. Finally, healthy control monocytes treated with DZNep plus TLR-8 induced strong production of alpha-smooth muscle actin in dermal fibroblasts, which was inhibited by TIMP-1-blocking antibody. CONCLUSION: These data demonstrate a novel role of histone demethylation induced by DZNep on Fra-2-mediated TIMP-1 production by monocytes in the presence of TLR-8 agonist. This consequently orchestrates the transdifferentiation of fibroblasts, a key event in the pathogenesis of SSc. PMID- 26814615 TI - Interleukin (IL)-17-producing pathogenic T lymphocytes co-express CD20 and are depleted by rituximab in primary Sjogren's syndrome: a pilot study. AB - Compelling evidence suggests that interleukin (IL)-17 and IL-17-producing cells play a pivotal role in the pathogenesis of primary Sjogren's syndrome (pSS). We investigated phenotypical and functional effects of the anti-CD20 antibody rituximab (RTX) on circulating and glandular IL-17-producing T cells in pSS. RTX is able to deplete glandular IL-17(+) CD3(+) CD4(-) CD8(-) double-negative (DN) and CD4(+) Th17 cells as well as circulating IL-17(+) DN T cells. A fraction of glandular and circulating IL-17(+) DN cells and CD4(+) T helper type 17 (Th17) cells co-expresses CD20 on the cell surface explaining, at least in part, such depletive capacity of RTX. The exposure to RTX does not rescue the in-vitro corticosteroid resistance of IL-17(+) DN T cells. Our results support further the therapeutic role in pSS of RTX that, despite its B cell specificity, appears able to also hamper IL-17-producing T cells in this disease. PMID- 26814617 TI - Identification of class II ADP-ribosylation factors as cellular factors required for hepatitis C virus replication. AB - GBF1 is a host factor required for hepatitis C virus (HCV) replication. GBF1 functions as a guanine nucleotide exchange factor for G-proteins of the Arf family, which regulate membrane dynamics in the early secretory pathway and the metabolism of cytoplasmic lipid droplets. Here we established that the Arf guanine nucleotide exchange factor activity of GBF1 is critical for its function in HCV replication, indicating that it promotes viral replication by activating one or more Arf family members. Arf involvement was confirmed with the use of two dominant negative Arf1 mutants. However, siRNA-mediated depletion of Arf1, Arf3 (class I Arfs), Arf4 or Arf5 (class II Arfs), which potentially interact with GBF1, did not significantly inhibit HCV infection. In contrast, the simultaneous depletion of both Arf4 and Arf5, but not of any other Arf pair, imposed a significant inhibition of HCV infection. Interestingly, the simultaneous depletion of both Arf4 and Arf5 had no impact on the activity of the secretory pathway and induced a compaction of the Golgi and an accumulation of lipid droplets. A similar phenotype of lipid droplet accumulation was also observed when GBF1 was inhibited by brefeldin A. In contrast, the simultaneous depletion of both Arf1 and Arf4 resulted in secretion inhibition and Golgi scattering, two actions reminiscent of GBF1 inhibition. We conclude that GBF1 could regulate different metabolic pathways through the activation of different pairs of Arf proteins. PMID- 26814618 TI - Infectious Complications in Children With Acute Myeloid Leukemia and Down Syndrome: Analysis of the Prospective Multicenter Trial AML-BFM 2004. AB - BACKGROUND: Children with acute myeloid leukemia (AML) and Down syndrome have high survival rates with intensity-reduced chemotherapeutic regimens, although the optimal balance between dose intensity and treatment toxicity has not been determined. We, therefore, characterized infectious complications in children with AML and Down syndrome treated according to AML-BFM 2004 study (ClinicalTrials.gov NCT00111345; amended 2006 for Down syndrome with reduced intensity). PROCEDURE: Data on infectious complications were gathered from the medical records in the hospital where the patient was treated. Infectious complications were categorized as fever without identifiable source (FUO), or as microbiologically or clinically documented infections. RESULTS: A total of 157 infections occurred in 61 patients (60.5% FUO, 9.6% and 29.9% clinically and microbiologically documented infections, respectively). Almost 90% of the pathogens isolated from the bloodstream were Gram-positive bacteria, and approximately half of them were viridans group streptococci. All seven microbiologically documented episodes of pneumonia were caused by viruses. Infection-related mortality was 4.9%, and all three patients died due to viral infection. CONCLUSIONS: Our data demonstrate that a reduced-intensity chemotherapeutic regimen in children with AML and Down syndrome is still associated with high morbidity. Although no patient died due to bacteria or fungi, viruses were responsible for all lethal events. Future studies, therefore, have to focus on the impact of viruses on morbidity and mortality of patients with AML and Down syndrome. PMID- 26814619 TI - Population genetics and ecological niche of invasive Aedes albopictus in Mexico. AB - The Asian tiger mosquito Aedes albopictus (Skuse), is one of the most invasive mosquito species worldwide. In Mexico it is now recorded in 12 states and represents a serious public health problem, given the recent introduction of Chikungunya on the southern border. The aim of this study was to analyze the population genetics of A. albopictus from all major recorded foci, and model its ecological niche. Niche similarity with that from its autochthonous distribution in Asia and other invaded countries were analyzed and its potential future expansion and potential human exposure in climate change scenarios measured. We analyzed 125 sequences of a 317 bp fragment of the cyt b gene from seven A. albopictus populations across Mexico. The samples belong to 25 haplotypes with moderate population structuring (Fst=0.081, p<0.02) and population expansion. The most prevalent haplotype, found in all principal sites, was shared with the USA, Brazil, France, Madagascar, and Reunion Island. The ecological niche model using Mexican occurrence records covers 79.7% of the country, and has an 83% overlap with the Asian niche projected to Mexico. Both Neotropical and Nearctic regions are included in the Mexican niche model. Currently in Mexico, 38.6 million inhabitants are exposed to A. albopictus, which is expected to increase to 45.6 million by 2070. Genetic evidence supports collection information that A. albopictus was introduced to Mexico principally by land from the USA and Central and South America. Prevalent haplotypes from Mexico are shared with most invasive regions across the world, just as there was high niche similarity with both natural and invaded regions. The important overlap with the Asian niche model suggests a high potential for the species to disperse to sylvatic regions in Mexico. PMID- 26814620 TI - Botulinum toxin type A for neuropathic pain in patients with spinal cord injury. AB - OBJECTIVE: To evaluate the analgesic effect of botulinum toxin type A (BTX-A) on patients with spinal cord injury-associated neuropathic pain. METHODS: The effect of BTX-A on 40 patients with spinal cord injury-associated neuropathic pain was investigated using a randomized, double-blind, placebo-controlled design. A 1 time subcutaneous BTX-A (200U) injection was administered to the painful area. Visual analogue scale (VAS) scores (0-100mm), the Korean version of the short form McGill Pain Questionnaire, and the World Health Organization WHOQOL-BREF quality of life assessment were evaluated prior to treatment and at 4 and 8 weeks after the injection. RESULTS: At 4 and 8 weeks after injection, the VAS score for pain was significantly reduced by 18.6 +/- 16.8 and 21.3 +/- 26.8, respectively, in the BTX-A group, whereas it was reduced by 2.6 +/- 14.6 and 0.3 +/- 19.5, respectively, in the placebo group. The pain relief was associated with preservation of motor or sensory function below the neurological level of injury. Among the responders in the BTX-A group, 55% and 45% reported pain relief of 20% or greater at 4 and 8 weeks, respectively, after the injection, whereas only 15% and 10% of the responders in the placebo group reported a similar level of pain relief. Improvements in the score for the physical health domain of the WHOQOL BREF in the BTX-A group showed a marginal trend toward significance (p = 0.0521) at 4 weeks after the injection. INTERPRETATION: These results indicate that BTX-A may reduce intractable chronic neuropathic pain in patients with spinal cord injury. PMID- 26814621 TI - Towards 5G: A Photonic Based Millimeter Wave Signal Generation for Applying in 5G Access Fronthaul. AB - 5G communications require a multi Gb/s data transmission in its small cells. For this purpose millimeter wave (mm-wave) RF signals are the best solutions to be utilized for high speed data transmission. Generation of these high frequency RF signals is challenging in electrical domain therefore photonic generation of these signals is more studied. In this work, a photonic based simple and robust method for generating millimeter waves applicable in 5G access fronthaul is presented. Besides generating of the mm-wave signal in the 60 GHz frequency band the radio over fiber (RoF) system for transmission of orthogonal frequency division multiplexing (OFDM) with 5 GHz bandwidth is presented. For the purpose of wireless transmission for 5G application the required antenna is designed and developed. The total system performance in one small cell was studied and the error vector magnitude (EVM) of the system was evaluated. PMID- 26814623 TI - Vitamin D - has the new dawn for dietary recommendations arrived? PMID- 26814624 TI - Stability indicating methods for the analysis of cefprozil in the presence of its alkaline induced degradation product. AB - Three simple, specific, accurate and precise spectrophotometric methods were developed for the determination of cefprozil (CZ) in the presence of its alkaline induced degradation product (DCZ). The first method was the bivariate method, while the two other multivariate methods were partial least squares (PLS) and spectral residual augmented classical least squares (SRACLS). The multivariate methods were applied with and without variable selection procedure (genetic algorithm GA). These methods were tested by analyzing laboratory prepared mixtures of the above drug with its alkaline induced degradation product and they were applied to its commercial pharmaceutical products. PMID- 26814625 TI - Comment on "Exposure to mercury and Aroclor 1268 congeners in least terns (Sternula antillarum) in coastal Georgia, USA" by G. L. Robinson, G. L. Mills, A. H. Lindell, S. H. Schweitzer and S. M. Hernandez, Environmental Science: Processes & Impacts, 2015, 17, 1424. AB - In a recent paper published in this journal (Robinson et al., Environmental Science: Processes & Impacts, 2015, 17, 1424), Robinson et al. reported concentrations of Aroclor 1268 congeners in least tern eggs in coastal Georgia, USA. This comment describes important omissions in Robinson et al.'s interpretation of those egg concentrations that alter the overall conclusions of the least tern study. PMID- 26814626 TI - Properties of Cerium Hydroxides from Matrix Infrared Spectra and Electronic Structure Calculations. AB - Reactions of laser ablated cerium atoms with hydrogen peroxide or hydrogen and oxygen mixtures diluted in argon and condensed at 4 K produced the Ce(OH)3 and Ce(OH)2 molecules and Ce(OH)2(+) cation as major products. Additional minor products were identified as the Ce(OH)4, HCeO, and OCeOH molecules. These new species were identified from their matrix infrared spectra with D2O2, D2, and (18)O2 isotopic substitution and correlating observed frequencies with values calculated by density functional theory. We find that the amounts of Ce(OH)3 and of the Ce(OH)2(+) cation increase on UV (lambda > 220 nm) photolysis, while Ce(OH)2, Ce(OH)4, and HCeO are photosensitive. The observed major species for Ce are in the +III or +II oxidation state, and the minor product, Ce(OH)4, is in the +IV oxidation state. The calculations for the vibrational frequencies with the B3LYP functional agree well with the experiment. The NBO analysis shows significant backbonding to the metal 4f and 5d orbitals for the closed shell species. Most open shell species have the excess spin in the 4f with paired spin in the 5d due to backbonding. The heats of formation of the observed species were derived from the available data from experiment and the calculated reaction energies. The major products in this study are different from similar reactions for Th where the tetrahydroxide was the major species. PMID- 26814628 TI - DNA based arithmetic function: a half adder based on DNA strand displacement. AB - Biomolecular programming utilizes the reactions and information stored in biological molecules, such as proteins and nucleic acids, for computational purposes. DNA has proven itself an excellent candidate for building logic operating systems due to its highly predictable molecular behavior. In this work we designed and realized an XOR logic gate and an AND logic gate based on DNA strand displacement reactions. These logic gates utilize ssDNA as input and output signals. The XOR gate and the AND gate were used as building blocks for constructing a half adder logic circuit, which is a primary step in constructing a full adder, a basic arithmetic unit in computing. This work provides the field of DNA molecular programming with a potential universal arithmetic tool. PMID- 26814629 TI - Isolation and detection of duck astrovirus CPH: implications for epidemiology and pathogenicity. AB - The transmission routes of duck astrovirus CPH (DAstV/CPH) and its pathogenicity in duck embryos were investigated. Using a reverse transcription-polymerase chain reaction (RT-PCR) developed in this study, DAstV/CPH was detected in 23/50 fresh droppings of breeder ducks, 39/65 breeding eggs, 26/31 dead embryos, and 6/10 newly hatched ducklings, which were taken from a Pekin duck farm where DAstV/CPH had previously been identified. This finding, and the detection of DAstV/CPH in 36/130 dead-in-shell duck embryo samples collected from different hatcheries located in six provinces, suggests that the virus may be horizontally and vertically transmitted and associated with hatchability problems. Inoculation and repeated passages in embryonating duck eggs resulted in isolation of DAstV/CPH. The virus caused severe chorioallantoic membrane lesions as well as growth retardation and embryo mortality, indicating that DAstV/CPH is pathogenic for duck embryos. The effect of DAstV/CPH on hatching was confirmed by an embryo infection experiment in which 8/10 9-day-old duck embryos inoculated with the third passage of DAstV/CPH were unable to hatch, with most embryos succumbing in the final stage of incubation. The use of RT-PCR on the hatched ducklings provided evidence that the embryos could develop into infected ducklings. PMID- 26814630 TI - The impact of psychiatric comorbidities on the length of hospital stay in patients with heart failure. AB - BACKGROUND: Heart failure (HF) is a major healthcare problem contributing significantly to hospital admission stays and National Health Service (NHS) spending. Reducing length of hospital stay (LoS) in HF is paramount in reducing this burden and is influenced by factors relating to the condition, sociodemographics and comorbidities. Psychiatric comorbidities are being increasingly identified amongst HF patients but their impact on LoS has not been studied in the UK. METHODS: We investigated the impact of psychiatric comorbidities on LoS amongst 31,760 HF patients admitted to hospitals in North England between 1st January 2000 and 31st March 2013 from the ACALM (Algorithm for Comorbidities, Associations, Length of stay and Mortality) study. The ACALM protocol uses ICD-10 and OPCS-4 coding to trace HF patients, psychiatric comorbidities and demographics including LoS. RESULTS: Amongst 31,760 HF patients mean LoS in the absence of psychiatric comorbidities was 11.2days. The presence of a psychiatric comorbidity increased LoS by 3.3days. Logistic regression accounting for age, gender and ethnicity showed that LoS was significantly longer in patients suffering from depression (3.4days, p<0.001), bipolar disorder (8.8days, p<0.001) and all types of dementia (4.2days, p<0.001). CONCLUSIONS: Our results demonstrate that psychiatric comorbidities have a significant and clinically important impact on LoS in HF patients in the UK. Clinicians should be actively aware of psychiatric conditions amongst HF patients and manage them to reduce LoS and ultimately the risk for patients and financial burden for the NHS. PMID- 26814632 TI - QRS duration predicts left ventricular systolic function following ST elevation myocardial infarction. PMID- 26814631 TI - Effects of functional genetic variants in PPARdelta encoding peroxisome proliferator-activated receptor delta on the risk of ischemic stroke in Chinese Han population. PMID- 26814633 TI - Combined ostium secundum type ASD and pulmonary arterial thromboembolism causing pulmonary artery enlargement, pulmonary hypertension and recurrent paradoxical cerebral embolism due to deep venous thrombosis. PMID- 26814634 TI - Randomized trials of closure of persistent foramen ovale (PFO) vs medical therapy for patients with cryptogenic stroke - Effect of lost-to-follow-up and withdrawal of consent. PMID- 26814635 TI - Non-adherence to antihypertensive medication: The role of mental and physical comorbidity. AB - BACKGROUND: Multiple parameters influence adherence to drug treatment, including socio-economic, healthcare, condition, therapy, and patient-related factors. However, studies of the impact of patient-related factors, particularly regarding comorbid conditions, have produced conflicting results. OBJECTIVES: To analyse the association between mental and physical comorbidity and non-adherence to antihypertensive medication in patients attending primary care, after including a comprehensive range of chronic comorbidities and potential confounders. METHODS: Cross-sectional study of 113,397 adults with a diagnosis of hypertension in 2010 assigned to the public health service of a region in northeastern Spain. Pharmacy billing records were linked to data from electronic health records at individual level. Non-adherence was defined as an antihypertensive medication possession ratio (MPR) <80%. Multivariable logistic regression models were used to estimate the odds ratio for non-adherence. Potential predictors included mental and physical comorbidity, age, sex, blood pressure level, nationality, rurality, polypharmacy, and number of visits to the GP and to different specialties. RESULTS: One fifth of the study population showed poor adherence levels. Female sex, younger age, foreign nationality, living in a rural area, low blood pressure levels, polypharmacy, and mental comorbidity were positively and significantly associated with non-adherence. Conversely, non-adherence was negatively and significantly associated with the presence of cardiovascular risk factors and higher annual rates of GP visits. CONCLUSION: The majority of patient-related determinants identified here (e.g., the presence of mental comorbidity, polypharmacy, foreign nationality) underscores the need for a patient- rather than a disease-centred care approach, as well as adequate physician-patient communication. PMID- 26814636 TI - The ApoA-I mimetic peptide FAMP promotes recovery from hindlimb ischemia through a nitric oxide (NO)-related pathway. AB - BACKGROUND/OBJECTIVE: HDL has various atheroprotective functions and improves endothelial function. Apolipoprotein A-I (apoA-I) is a major protein of HDL and plays a crucial role in HDL functions. We developed a novel apoA-I mimetic peptide, FAMP (Fukuoka University ApoA-I Mimetic Peptide). It is unclear whether an apoA-I mimetic peptide can promote neovascularization in vivo. Here, we investigated the effect of FAMP on endothelial nitric oxide synthase (eNOS) activation and angiogenesis in a murine hindlimb ischemia model. METHODS AND RESULTS: Intramuscular administration of FAMP significantly enhanced blood flow recovery and increased capillary density in the ischemic limb of mice fed a high cholesterol diet (HCD). In a gait analysis, FAMP ameliorated functional recovery compared with that in the control group. FAMP significantly activated Akt, ERK, and eNOS phosphorylation in endothelial cells, and improved the migratory functions of human aortic endothelial cells (HAECs). LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), significantly inhibited the activation of eNOS by FAMP. FAMP had no beneficial effects on blood flow recovery in eNOS(-/-) mice. CONCLUSIONS: FAMP promoted recovery from hindlimb ischemia through a nitric oxide (NO)-related pathway by activation of a PI3K/Akt pathway. FAMP may become a new therapeutic agent for the future clinical treatment of critical limb ischemia (CLI). PMID- 26814637 TI - Microfluidic cell surface antigen expression analysis using a single antibody type. AB - Antigen expression plays a significant role in clinical studies, pathology, biology and chemistry. The type and degree of antigen expression can provide information for disease diagnosis/monitoring and is used for phenotype analysis of cells. In this work, an affinity capture method was developed to capture cells based on antigen expression differences in a single microfluidic chip. Microfluidic chips with two affinity regions-at different antibody concentrations captured two cell types based on differences in the expression of a single antigen. Using herringbone-modified capture channels, a separation purity of 95% and a capture efficiency of 15% were achieved under continuous-flow conditions. We observed that the capture ratio of Ramos B lymphocytes and HuT 78 T lymphocytes matched the expression ratio of CD71 for the two cell lines (R(2) = 0.94). To further validate our analytical method, Ramos B lymphocytes were spiked into blood samples to demonstrate performance with a complex sample. Expression ratios matched conventional flow cytometry measurements over a 40-fold difference, and the sample enrichment was 9.5*. This method has proven to be a robust system to measure the differences in antigen expression, and can be used to distinguish cells without having a unique surface antigen if the expression level is sufficiently high in one cell type. PMID- 26814638 TI - Membrane Interactions, Ligand-Dependent Dynamics, and Stability of Cytochrome P4503A4 in Lipid Nanodiscs. AB - Membrane-bound cytochrome P4503A4 (CYP3A4) is the major source of enzymatic drug metabolism. Although several structural models of CYP3A4 in various ligand complexes are available, none includes a lipid bilayer. Details of the effects of the membrane on protein dynamics and solvation, and access channels for ligands, remain uncertain. H/D exchange mass spectrometry (H/DXMS) with ligand free CYP3A4 containing a deletion of residues 3-12, compared to that of the full length wild type, in lipid nanodiscs afforded 91% sequence coverage. Deuterium exchange was fast in the F- and G-helices, HI loop, and C-terminal loop. In contrast, there is very low exchange in the F'- and G'-helices. The results are consistent with the overall membrane orientation of CYP3A4 suggested by published MD simulations and spectroscopic results, and the solvent accessibility of the F/G loop suggests that it is not deeply membrane-embedded. Addition of ketoconazole results in only modest, but global, changes in solvent accessibility. Interestingly, with ketoconazole bound some peptides become less solvent accessible or dynamic, including the F- and G-helices, but several peptides demonstrate modestly increased accessibility. Differential scanning calorimetry (DSC) of CYP3A4 nanodiscs suggests membrane-induced stabilization compared to that of aggregated CYP3A4 in buffer, and this stabilization is enhanced upon addition of the ligand ketoconazole. This ligand-induced stabilization is accompanied by a very large increase in DeltaH for CYP3A4 denaturation in nanodiscs, possibly due to increased CYP3A4-membrane interactions. Together, the results suggest a distinct orientation of CYP3A4 on the lipid membrane, and they highlight likely solvent access channels, which are consistent with several MD simulations. PMID- 26814639 TI - Two competitive nucleation mechanisms of calcium carbonate biomineralization in response to surface functionality in low calcium ion concentration solution. AB - Four self-assembled monolayer surfaces terminated with -COOH, -OH, -NH2 and -CH3 functional groups are used to direct the biomineralization processes of calcium carbonate (CaCO3) in low Ca(2+) concentration, and the mechanism of nucleation and initial crystallization within 12 h was further explored. On -COOH surface, nucleation occurs mainly via ion aggregation mechanism while prenucleation ions clusters may be also involved. On -OH and -NH2 surfaces, however, nucleation forms via calcium carbonate clusters, which aggregate in solution and then are adsorbed onto surfaces following with nucleation of amorphous calcium carbonate (ACC). Furthermore, strongly negative-charged -COOH surface facilitates the direct formation of calcites, and the -OH and -NH2 surfaces determine the formation of vaterites with preferred crystalline orientations. Neither ACC nor crystalline CaCO3 is observed on -CH3 surface. Our findings present a valuable model to understand the CaCO3 biomineralization pathway in natural system where functional groups composition plays a determining role during calcium carbonate crystallization. PMID- 26814640 TI - Commercial enzyme-linked immunosorbent assay versuspolymerase chain reaction for the diagnosis of chronic Chagas disease: a systematic review and meta-analysis. AB - Chronic Chagas disease diagnosis relies on laboratory tests due to its clinical characteristics. The aim of this research was to review commercial enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) diagnostic test performance. Performance of commercial ELISA or PCR for the diagnosis of chronic Chagas disease were systematically searched in PubMed, Scopus, Embase, ISI Web, and LILACS through the bibliography from 1980-2014 and by contact with the manufacturers. The risk of bias was assessed with QUADAS-2. Heterogeneity was estimated with the I2 statistic. Accuracies provided by the manufacturers usually overestimate the accuracy provided by academia. The risk of bias is high in most tests and in most QUADAS dimensions. Heterogeneity is high in either sensitivity, specificity, or both. The evidence regarding commercial ELISA and ELISA-rec sensitivity and specificity indicates that there is overestimation. The current recommendation to use two simultaneous serological tests can be supported by the risk of bias analysis and the amount of heterogeneity but not by the observed accuracies. The usefulness of PCR tests are debatable and health care providers should not order them on a routine basis. PCR may be used in selected cases due to its potential to detect seronegative subjects. PMID- 26814641 TI - Genetic diversity of Cryptosporidium identified in clinical samples from cities in Brazil and Argentina. AB - The identification and characterisation of Cryptosporidium genotypes and subtypes are fundamental to the study of cryptosporidiosis epidemiology, aiding in prevention and control strategies. The objective was to determine the genetic diversity of Cryptosporidium in samples obtained from hospitals of Rio de Janeiro, Brazil, and Buenos Aires, Argentina. Samples were analysed by microscopy and TaqMan polymerase chain reaction (PCR) assays for Cryptosporidium detection, genotyped by nested-PCR-restriction fragment length polymorphism (RFLP) analysis of the 18S rRNA gene and subtyped by DNA sequencing of the gp60 gene. Among the 89 samples from Rio de Janeiro, Cryptosporidium spp were detected in 26 by microscopy/TaqMan PCR. In samples from Buenos Aires,Cryptosporidium was diagnosed in 15 patients of the 132 studied. The TaqMan PCR and the nested-PCR-RFLP detected Cryptosporidium parvum, Cryptosporidium hominis, and co-infections of both species. In Brazilian samples, the subtypes IbA10G2 and IIcA5G3 were observed. The subtypes found in Argentinean samples were IbA10G2, IaA10G1R4, IaA11G1R4, and IeA11G3T3, and mixed subtypes of Ia and IIa families were detected in the co-infections. C. hominis was the species more frequently detected, and subtype family Ib was reported in both countries. Subtype diversity was higher in Buenos Aires than in Rio de Janeiro and two new subtypes were described for the first time. PMID- 26814642 TI - Polyphasic characterisation of Burkholderia cepaciacomplex species isolated from children with cystic fibrosis. AB - Cystic fibrosis (CF) patients with Burkholderia cepacia complex (Bcc) pulmonary infections have high morbidity and mortality. The aim of this study was to compare different methods for identification of Bcc species isolated from paediatric CF patients. Oropharyngeal swabs from children with CF were used to obtain isolates of Bcc samples to evaluate six different tests for strain identification. Conventional (CPT) and automatised (APT) phenotypic tests, polymerase chain reaction (PCR)-recA, restriction fragment length polymorphism recA, recA sequencing, and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) were applied. Bacterial isolates were also tested for antimicrobial susceptibility. PCR-recA analysis showed that 36 out of the 54 isolates were Bcc. Kappa index data indicated almost perfect agreement between CPT and APT, CPT and PCR-recA, and APT and PCR-recA to identify Bcc, and MALDI TOF and recA sequencing to identify Bcc species. The recA sequencing data and the MALDI-TOF data agreed in 97.2% of the isolates. Based on recA sequencing, the most common species identified were Burkholderia cenocepacia IIIA (33.4%),Burkholderia vietnamiensis (30.6%), B. cenocepaciaIIIB (27.8%), Burkholderia multivorans (5.5%), and B. cepacia (2.7%). MALDI-TOF proved to be a useful tool for identification of Bcc species obtained from CF patients, although it was not able to identify B. cenocepacia subtypes. PMID- 26814643 TI - Spatial distribution of triatomines in domiciles of an urban area of the Brazilian Southeast Region. AB - Reports of triatomine infestation in urban areas have increased. We analysed the spatial distribution of infestation by triatomines in the urban area of Diamantina, in the state of Minas Gerais, Brazil. Triatomines were obtained by community-based entomological surveillance. Spatial patterns of infestation were analysed by Ripley's K function and Kernel density estimator. Normalised difference vegetation index (NDVI) and land cover derived from satellite imagery were compared between infested and uninfested areas. A total of 140 adults of four species were captured (100 Triatoma vitticeps, 25 Panstrongylus geniculatus, 8 Panstrongylus megistus, and 7 Triatoma arthurneivai specimens). In total, 87.9% were captured within domiciles. Infection by trypanosomes was observed in 19.6% of 107 examined insects. The spatial distributions ofT. vitticeps, P. geniculatus, T. arthurneivai, and trypanosome-positive triatomines were clustered, occurring mainly in peripheral areas. NDVI values were statistically higher in areas infested by T. vitticeps and P. geniculatus. Buildings infested by these species were located closer to open fields, whereas infestations of P. megistus and T. arthurneivai were closer to bare soil. Human occupation and modification of natural areas may be involved in triatomine invasion, exposing the population to these vectors. PMID- 26814644 TI - First description of Candida nivariensis in Brazil: antifungal susceptibility profile and potential virulence attributes. AB - This study evaluated the antifungal susceptibility profile and the production of potential virulence attributes in a clinical strain of Candida nivariensis for the first time in Brazil, as identified by sequencing the internal transcribed spacer (ITS)1-5.8S-ITS2 region and D1/D2 domains of the 28S of the rDNA. For comparative purposes, tests were also performed with reference strains. All strains presented low planktonic minimal inhibitory concentrations (PMICs) to amphotericin B (AMB), caspofungin (CAS), and voriconazole. However, our strain showed elevated planktonic MICs to posaconazole (POS) and itraconazole, in addition to fluconazole resistance. Adherence to inert surfaces was conducted onto glass and polystyrene. The biofilm formation and antifungal susceptibility on biofilm-growing cells were evaluated by crystal violet staining and a XTT reduction assay. All fungal strains were able to bind both tested surfaces and form biofilm, with a binding preference to polystyrene (p < 0.001). AMB promoted significant reductions (~50%) in biofilm production by our C. nivariensis strain using both methodologies. This reduction was also observed for CAS and POS, but only in the XTT assay. All strains were excellent protease producers and moderate phytase producers, but lipases were not detected. This study reinforces the pathogenic potential of C. nivariensis and its possible resistance profile to the azolic drugs generally used for candidiasis management. PMID- 26814645 TI - Malaria in gold-mining areas in Colombia. AB - Gold-mining may play an important role in the maintenance of malaria worldwide. Gold-mining, mostly illegal, has significantly expanded in Colombia during the last decade in areas with limited health care and disease prevention. We report a descriptive study that was carried out to determine the malaria prevalence in gold-mining areas of Colombia, using data from the public health surveillance system (National Health Institute) during the period 2010-2013. Gold-mining was more prevalent in the departments of Antioquia, Cordoba, Bolivar, Choco, Narino, Cauca, and Valle, which contributed 89.3% (270,753 cases) of the national malaria incidence from 2010-2013 and 31.6% of malaria cases were from mining areas. Mining regions, such as El Bagre, Zaragoza, and Segovia, in Antioquia, Puerto Libertador and Montelibano, in Cordoba, and Buenaventura, in Valle del Cauca, were the most endemic areas. The annual parasite index (API) correlated with gold production (R2 0.82, p < 0.0001); for every 100 kg of gold produced, the API increased by 0.54 cases per 1,000 inhabitants. Lack of malaria control activities, together with high migration and proliferation of mosquito breeding sites, contribute to malaria in gold-mining regions. Specific control activities must be introduced to control this significant source of malaria in Colombia. PMID- 26814646 TI - The dynamics of Brazilian protozoology over the past century. AB - Brazilian scientists have been contributing to the protozoology field for more than 100 years with important discoveries of new species such as Trypanosoma cruzi and Leishmania spp. In this work, we used a Brazilian thesis database (Coordination for the Improvement of Higher Education Personnel) covering the period from 1987-2011 to identify researchers who contributed substantially to protozoology. We selected 248 advisors by filtering to obtain researchers who supervised at least 10 theses. Based on a computational analysis of the thesis databases, we found students who were supervised by these scientists. A computational procedure was developed to determine the advisors' scientific ancestors using the Lattes Platform. These analyses provided a list of 1,997 researchers who were inspected through Lattes CV examination and allowed the identification of the pioneers of Brazilian protozoology. Moreover, we investigated the areas in which researchers who earned PhDs in protozoology are now working. We found that 68.4% of them are still in protozoology, while 16.7% have migrated to other fields. We observed that support for protozoology by national or international agencies is clearly correlated with the increase of scientists in the field. Finally, we described the academic genealogy of Brazilian protozoology by formalising the "forest" of Brazilian scientists involved in the study of protozoa and their vectors over the past century. PMID- 26814647 TI - Spread of Phlebotominae in temperate climates: province of Cordoba, Argentina. AB - We report the presence of the competent vector for Leishmania spp, Migonemyia migonei, and the Evandromyia cortelezzii-sallesi complex south of its known distribution in the central temperate region of Argentina, in the province of Cordoba. The persistence of this phlebotomine in the northern border of the province, its association with a case of cutaneous leishmaniasis, and the new record in the outskirts of the city of Cordoba, the second most populated in the country, strengthens the need for regular vector surveillance and a case detection-sensitive health system in vulnerable regions, even in temperate climates. PMID- 26814648 TI - The mitogenome of Onchocerca volvulus from the Brazilian Amazonia focus. AB - We report here the first complete mitochondria genome of Onchocerca volvulus from a focus outside of Africa. An O. volvulus mitogenome from the Brazilian Amazonia focus was obtained using a combination of high-throughput and Sanger sequencing technologies. Comparisons made between this mitochondrial genome and publicly available mitochondrial sequences identified 46 variant nucleotide positions and suggested that our Brazilian mitogenome is more closely related to Cameroon origin mitochondria than West African-origin mitochondria. As well as providing insights into the origins of Latin American onchocerciasis, the Brazilian Amazonia focus mitogenome may also have value as an epidemiological resource. PMID- 26814650 TI - Current and novel biomarkers in heart failure: bench to bedside. AB - PURPOSE OF REVIEW: Natriuretic peptides, high-sensitivity cardiac troponins, and suppression of tumorigenicity 2 are novel biomarkers that reflect the intricate pathophysiology of heart failure and can thus be used for the diagnosis, management, and prognosis of heart failure. RECENT FINDINGS: This review article describes the significance of B-type natriuretic peptide (BNP), N-terminal prohormone of BNP, ST2, and cardiac troponins. We outline their new roles in guiding the management of heart failure as well as strong prognostic indicators for adverse cardiovascular outcomes. SUMMARY: By recognizing the diagnostic and prognostic significance of these biomarkers, clinicians can utilize these biomarkers to more accurately evaluate and risk stratify patients. These markers can also be used to help guide the medical management of heart failure. The best approach for an accurate diagnosis, management, and prognosis of heart failure will likely involve a multimarker panel of biomarkers, which may include high sensitivity troponins, BNP, N-terminal prohormone of BNP, and ST2. PMID- 26814649 TI - Microevolution of Outbreak-Associated Middle East Respiratory Syndrome Coronavirus, South Korea, 2015. AB - During the 2015 Middle East respiratory syndrome coronavirus outbreak in South Korea, we sequenced full viral genomes of strains isolated from 4 patients early and late during infection. Patients represented at least 4 generations of transmission. We found no evidence of changes in the evolutionary rate and no reason to suspect adaptive changes in viral proteins. PMID- 26814651 TI - Year in review: mitral valve surgery. AB - PURPOSE OF REVIEW: In the past year, there has been progress on several fronts in the field of mitral valve surgery and intervention. Here, we review key publications regarding the surgical and transcatheter management of mitral valve disease. RECENT FINDINGS: This past year heralded the publication of the 2014 American Heart Association (AHA)/American College of Cardiology (ACC) Guidelines for the Management of Patients With Valvular Heart Disease. Regarding degenerative mitral regurgitation, low risk of operative mortality and data demonstrating clinical benefit for early surgery are prompting renewed calls for early intervention before guideline-based triggers. For functional mitral regurgitation, the precise roles of chordal-sparing replacement versus repair and the optimal management of moderate disease at the time of surgical revascularization are unclear. Sternal-sparing minimally invasive mitral valve surgery has become a mature procedure in experienced centers and offers comparable surgical morbidity and mortality with superior cosmesis and faster return to baseline function. Transcatheter interventions for mitral regurgitation continue to undergo development and testing. Mounting experience and ongoing clinical trials with the MitraClip endovascular edge-to-edge repair device will provide important data on the optimal target population for this device. SUMMARY: This past year has seen important advances in the surgical treatment of degenerative and functional mitral regurgitation as well as continued refinement of transcatheter interventions. PMID- 26814652 TI - Year in review: complex valve reconstruction. AB - PURPOSE OF REVIEW: In recent years, great emphasis has been placed on reconstructive techniques for the surgical management of heart valve disease. In this review, we discuss recent data and current practice as it pertains to the subject of reconstructive valve surgery. RECENT FINDINGS: New techniques and an improved understanding of the mechanisms of aortic insufficiency have led to marked improvement in the early and late outcomes of aortic valve repair. While mitral valve repair is the established approach for the management of degenerative mitral valve disease, surgical technique continues to be refined, with valve reconstruction principles applied to increasingly challenging anatomy. Moreover, the introduction of novel biomaterials has allowed extension of the indication for valve reconstruction to circumstances of extensive tissue defect, including infective endocarditis. SUMMARY: Valve reconstruction is increasingly being recognized as an alternative to valve replacement. It alleviates the risks of prosthesis-related complications and is especially appealing in young and middle-aged adults. While early and midterm outcomes appear promising, further studies are warranted to assess the clinical benefit and long-term durability of complex valve reconstruction procedures. PMID- 26814653 TI - APPLICATION OF T-TECHNIQUE FACTOR ANALYSIS TO THE STOCK MARKET. AB - Proportional changes in the prices of 425 individual common stocks were recorded for each of 44 quarter-year periods. After normalization of the data for each stock, sums of cross-products were computed among the time periods across stocks. Factor analysis of the cross-product matrix yielded seven factors. By cumulating the factor loadings successively over the 44 quarters, so as to simulate absolute values rather than change scores, six of these factors appear to be generated by the simplicial nature of the cross-product matrix, while the seventh was an expected factor representing general stock market strengths and weaknesses. Some possibilities for pre- diction are discussed, but little in the way of direct prediction of stock market fluctuations is supported by these findings. PMID- 26814654 TI - TESTING CONDITIONS AND THE MEASUREMENT PRESCHOOL CHILDREN OF CREATIVE ABILITIES IN LOWER-CLASS. AB - The effects of play-like, verbal-feedback, and nonverbal-feedback testing conditions on three creakive ability, measures were studied using 176 lower- class preschool children. Most of the creativity measures used were unaffected by variations in testing conditions. In addition, different forms of the creativ- ity measures hypothesized to be parallel proved to have only weak relationships with each other. However, split-half reliabilities of the individual measures were fairly high. PMID- 26814655 TI - SECOND ORDER ANALYSIS OF COMREY'S ELEVEN FACTOR SOLUTION. AB - A second order analysis was conducted on the Comrey inventory. The analysis did not approach an adequate solution until eight factors were isolated. The eight factor solution was rejected on the basis that it com- pressed major factors while exaggerating he importance of minor factors. PMID- 26814656 TI - SIMULTANEOUS PROCESSING OF TYPAL AND DIMENSIONAL VARIATION AMONG MULTIDIMENSIONAL EVENTS. AB - If class structure exists within a multidimensional configuration, two sources of variation among elements are potentially present: typed variation due to class membership and dimensional variation due to inter-element differences unrelated to this structure. The simultaneous processing of both sources of variation among a set of multidimensional visual pattern was examined. Similarity judgments to pairs of 14 polygons arising from two physical classes were scaled with the TORSCA nometric MDS procedure. No evidence was found for processing of dimensional variation in the vari-max-rotated TORSCA solutions. However, Degerman rotation of TORSCA solutions led to recovery of both sources of variation. Confirmatory regression andysis based on physical measures of typal and dimensional variation among patterns indicated the appropriateness of the Degerman rotation. PMID- 26814657 TI - THE ASSUMPTIONS OF CAUSAL ANALYSES FOR INCOMPLETE CAUSAL SETS OF TWO MULTILEVEL VARIABLES. AB - aThree causal analyses of correlations: the two-stage partial correlation analysis of Pelz and Andrews (1964); the cross-lagged panel correlation analysis of Campbell and Stanley (1963), Campbell (1963), and Rozelle and Campbell (1969); and a new three-stage analysis described in this paper are evaluated in terms of causal models representing any two variables which constitute an incomplete causal set. It is found t h a t the first two analyses make assumptions which are not generally true and which are not presently subject to practical tests. The third i s found to be useful as a way of finding out whether the correlation between two variables i s due entirely to third variable causation. PMID- 26814658 TI - THE ETA COEFFICIENT IN MANOVA. AB - Methods for the calculation of eta squared have recently been presented for examining the strength of relationship in univariate analysis of variance. This paper extends them to the multivariate used in which the effects of independent variables may be examined in relation to two or more dependent variables and presents considerations for the calculation, use, and interpretation of the coefficients. The concepts of eta squared are generalized to the rnultivaziate case through the application of the multivariate general linear hypothesis Both orthogronal and nonorthogonal solutions are considered and an example of the former is presented. PMID- 26814659 TI - GLOBAL MEASURES OF ASSOCIATION IN MULTIVARIATE ANALYSIS OF VARIANCE. AB - Four possible global measures of association for estimating strength of association in MANOVA are presented, One of them, Wilks's generalization of eta squared, is rejected because of undesirable properties. Of the other three, one in- volves Wilks's Lamda, with the remaining two involving the trace statistic V. It is now that an unbiased estimate can be obtained for V, and hence that the global measure involving this unbiased estimate might be the best. Finally, an algebraic demonstration showed that the estimates of association obtained from the three measures will generally differ by only a few percent or less. PMID- 26814660 TI - A MONTE CARLO STUDY OF THE ACCURACY OF A HIERARCHICAL GROUPING PROCEDURE. AB - The accuracy of the Ward-Hook method of hierarchical grouping was studied using artificial data sampled from a mixture distribution. The expected number of sample misclassifications as well as the variance of these mimlassifications were taken as the criteria of subgrouping accuracy. It was found that the expected sample misclassificatiun rate was a positively biased estimator of the population probability of misclassifioartion. Further, by in- c d n g sample size, the variance of the sample misclassifications decreased. Accurate subgroupings were found in geneml when the population misclassification rake was very low (.02). When this probability was increased to .20, the misclassification variance increased sharply, unless sample size was large. PMID- 26814661 TI - NOTE ON THE EQUIVALENCE OF THE SIGNIFICANCE TEST OF THE PARTIAL POINT-BISERIAL CORRELATION AND THE ONE-FACTOR ANALYSIS OF COVARIANCE FOR TWO TREATMENT GROUPS. AB - An identity is demonstrated between (1) the squared Student's t-statistic obtained as a transformation of the sample point-biserial correlation coefficient relating dichotomous variable, 21, to continuous variable x, with the effects of a third variable, x, partialed out; and (2) the F-statistic resulting from a one factor, two-group (the y dichotomy) analysis of covariance on the x variable Mth the third variable, x, covaried. PMID- 26814662 TI - BRIEF REPORT: PSYCHOLINGUISTIC PERFORMANCE AS AN INDICATOR OF MODERNIZATION. AB - The Illinois Test of Psycholinguistic Abilities (ITPA) was administered to 80 Ss from four cultural systems of varying degrees of modernization in Sierra Leone. Extensive univariate results were reporbed by Karr (1969). This short note indicates the utility of muliivariate analyses. Multiple dis- criminant analysis was applied to the nine ITPA subtests, resulting in two significant discriminsant functions. The first function separated the groups along the hypothesized modernization continuum. The second function in- dicated one way in which bhe hypothesized levels of modernization did not hold up under empirical investigation. PMID- 26814663 TI - Microfluidic Assembly of pDNA/Cationic Liposome Lipoplexes with High pDNA Loading for Gene Delivery. AB - Microfluidics offers unique characteristics to control the mixing of liquids under laminar flow. Its use for the assembly of lipoplexes represents an attractive alternative for the translation of gene delivery studies into clinical trials on a sufficient throughput scale. Here, it was shown that the microfluidic assembly of pDNA/cationic liposome (CL) lipoplexes allows the formation of nanocarriers with enhanced transfection efficiencies compared with the conventional bulk-mixing (BM) process under high pDNA loading conditions. Lipoplexes generated by microfluidic devices exhibit smaller and more homogeneous structures at a molar charge ratio (R+/-) of 1.5, representing the ratio of lipid to pDNA content. Using an optimized model to fit small-angle X-ray scattering (SAXS) curves, it was observed that large amounts of pDNA induces the formation of aggregates with a higher number of stacked bilayers (N ~ 5) when the BM process was used, whereas microfluidic lipoplexes presented smaller structures with a lower number of stacked bilayers (N ~ 2.5). In vitro studies further confirmed that microfluidic lipoplexes achieved higher in vitro transfection efficiencies in prostate cancer cells at R +/- 1.5, employing a reduced amount of cationic lipid. The correlation of mesoscopic characteristics with in vitro performance provides insights for the elucidation of the colloidal arrangement and biological behavior of pDNA/CL lipoplexes obtained by different processes, highlighting the feasibility of applying microfluidics to gene delivery. PMID- 26814664 TI - Low Temperature Rate Constants for the Reactions of O((1)D) with N2, O2, and Ar. AB - The kinetics of the gas-phase quenching reactions O((1)D) + N2, O((1)D) + O2, and O((1)D) + Ar have been studied over the 50-296 K temperature range using the Laval nozzle method. O((1)D) atoms were created in situ by the pulsed photolysis of O3 precursor molecules at 266 nm. Rate constants for these processes were measured directly, following the decay of O((1)D) atoms through vacuum ultraviolet laser-induced fluorescence at 115.215 nm. For the O((1)D) + N2 and O((1)D) + O2 reactions, the quenching efficiencies are seen to increase as the temperature falls. For the O((1)D) + N2 system, this indicates the likely influence of the intermediate complex lifetime on the quenching rate through nonadiabatic processes. For the O((1)D) + O2 system, which is considerably more complex, this behavior could result from the interactions between several potential energy surfaces. PMID- 26814665 TI - Absolute Quantitative MALDI Imaging Mass Spectrometry: A Case of Rifampicin in Liver Tissues. AB - Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) elucidates molecular distributions in thin tissue sections. Absolute pixel to-pixel quantitation has remained a challenge, primarily lacking validation of the appropriate analytical methods. In the present work, isotopically labeled internal standards are applied to tissue sections to maximize quantitative reproducibility and yield accurate quantitative results. We have developed a tissue model for rifampicin (RIF), an antibiotic used to treat tuberculosis, and have tested different methods of applying an isotopically labeled internal standard for MALDI IMS analysis. The application of the standard and subsequently the matrix onto tissue sections resulted in quantitation that was not statistically significantly different from results obtained using HPLC-MS/MS of tissue extracts. Quantitative IMS experiments were performed on liver tissue from an animal dosed in vivo. Each microspot in the quantitative images measures the local concentration of RIF in the thin tissue section. Lower concentrations were detected from the blood vessels and around the portal tracts. The quantitative values obtained from these measurements were comparable (>90% similarity) to HPLC MS/MS results obtained from extracts of the same tissue. PMID- 26814666 TI - PET-CT with MR Fusion: Single Comprehensive Preoperative Metastatic Workup in Head and Neck Malignancy: A Case Report. AB - Head neck cancers (HNC) are the sixth most common cancer worldwide. In presence of the complex anatomy of this region, early diagnosis can sometimes be a challenge. At present for the TNM staging, contrast enhanced CT and MRI are the primary imaging modalities for evaluating T stage of HNSCC. Multiple studies suggest that PET/CT might be superior to conventional imaging (CT or MRI) in initial staging and may alter management and treatment especially when distant metastases are discovered. We present a case of a 35-year-old patient who presented to us with an ulcerative lesion on the left buccal mucosa, which was staged as cT2N0M0, using the conventional radiology. But on subsequent imaging by PET-CT with MR-fusion was upstaged to cT4bN0M0, thus completely changing the management of the patient. With the recent advances in technology leading to fusion of MRI images with PET-CT images have combined the benefits of all three imaging modalities and has led to increased sensitivity towards soft tissue and peri-neural invasion of tumours leading to upstaging of primary oral cavity malignancies, altering their management. Accuracy is increased when the information of multiple imaging modalities are analysed together and has the potential of changing the management plan of patients. PMID- 26814667 TI - Long-Term Seasonal and Interannual Patterns of Marine Mammal Strandings in Subtropical Western South Atlantic. AB - Understanding temporal patterns of marine mammal occurrence is useful for establishing conservation strategies. We used a 38 yr-long dataset spanning 1976 to 2013 to describe temporal patterns and trends in marine mammal strandings along a subtropical stretch of the east coast of South America. This region is influenced by a transitional zone between tropical and temperate waters and is considered an important fishing ground off Brazil. Generalized Additive Models were used to evaluate the temporal stranding patterns of the most frequently stranded species. Forty species were documented in 12,540 stranding events. Franciscana (n = 4,574), South American fur seal, (n = 3,419), South American sea lion (n = 2,049), bottlenose dolphins (n = 293) and subantarctic fur seal (n = 219) were the most frequently stranded marine mammals. The seasonality of strandings of franciscana and bottlenose dolphin coincided with periods of higher fishing effort and strandings of South American and subantarctic fur seals with post-reproductive dispersal. For South American sea lion the seasonality of strandings is associated with both fishing effort and post-reproductive dispersal. Some clear seasonal patterns were associated with occurrence of cold- (e.g. subantarctic fur seal) and warm-water (e.g. rough-toothed dolphin) species in winter and summer, respectively. Inter-annual increases in stranding rate were observed for franciscana and South American fur seal and these are likely related to increased fishing effort and population growth, respectively. For subantarctic fur seal the stranding rate showed a slight decline while for bottlenose dolphin it remained steady. No significant year to year variation in stranding rate was observed for South American sea lion. The slight decrease in frequency of temperate/polar marine mammals and the increased occurrence of subtropical/tropical species since the late 1990s might be associated with environmental changes linked to climate change. This long-term study indicates that temporal stranding patterns of marine mammals might be explained by either fishing-related or environmental factors. PMID- 26814668 TI - Strain-Induced Ferroelectric Topological Insulator. AB - Ferroelectricity and band topology are two extensively studied yet distinct properties of insulators. Nonetheless, their coexistence has never been observed in a single material. Using first-principles calculations, we demonstrate that a noncentrosymmetric perovskite structure of CsPbI3 allows for the simultaneous presence of ferroelectric and topological orders with appropriate strain engineering. Metallic topological surface states create an intrinsic short circuit condition, helping stabilize bulk polarization. Exploring diverse structural phases of CsPbI3 under pressure, we identify that the key structural feature for achieving a ferroelectric topological insulator is to suppress PbI6 cage rotation in the perovskite structure, which could be obtained via strain engineering. Ferroelectric control over the density of topological surface states provides a new paradigm for device engineering, such as perfect-focusing Veselago lens and spin-selective electron collimator. Our results suggest that CsPbI3 is a simple model system for ferroelectric topological insulators, enabling future studies exploring the interplay between conventional symmetry-breaking and topological orders and their novel applications in electronics and spintronics. PMID- 26814669 TI - Chemical diversity of labdane-type bicyclic diterpene biosynthesis in Actinomycetales microorganisms. AB - Five pairs of bacterial type-A and type-B diterpene synthases have been characterized: BAD86798/BAD86797, AHK61133/AHK61132, BAB39207/BAB39206, CldD/CldB and RmnD/RmnB, and are involved in the formation of pimara-9(11),15-diene, terpente-3,13,15-triene and labda-8(17),12(E),14-triene. Mining of bacterial genome data revealed an additional four pairs of type-A and type-B diterpene synthases: Sros_3191/Sros_3192 of Streptosporangium roseum DSM 43021, Sare_1287/Sare_1288 of Salinispora arenicola CNS-205, SCLAV_5671/SCLAV_5672 and SCLAV_p0491/SCLAV_p0490 of Streptomyces clavuligerus ATCC 27064. Since SCLAV_p0491/SCLAV_p0490 is similar to the labdane-type diterpene synthase pairs, CldD/CldB and RmnD/RmnB based on the alignment of the deduced amino acid sequences and phylogenetic analyses of the aligned sequences, these predicted diterpene synthases were characterized by an enzymatic reaction using a pair of recombinant type-A and type-B diterpene synthases prepared in Escherichia coli and the heterologous expression of two genes encoding type-A and type-B diterpene synthases in an engineered Streptomyces host. The generation of labda 8(17),12(E),14-triene (1) by CldB and CldD was reconfirmed by enzymatic synthesis. Furthermore, labda-8(17),13(16),14-triene (2) was generated by SCLAV_p0491 and CldB, and ladba-7,12(E),14-triene (3) by CldD and SCLAV_p0490. SCLAV_p0491 and SCLAV_p0490 catalyzed the generation of the novel diterpene hydrocarbon, labda-7,13(16),14-triene (4). PMID- 26814670 TI - Enantioselective total synthesis of naturally occurring eushearilide and evaluation of its antifungal activity. AB - The asymmetric total synthesis of a newly proposed structure of (3S,16E,20E,23S) (+)-eushearilide was achieved primarily through an asymmetric Mukaiyama aldol reaction, Schlosser-modified Wittig reaction and 2-methyl-6-nitrobenzoic anhydride-mediated macrolactonization. Based on detailed spectroscopic analyses, the obtained synthetic compound was found to be identical to natural eushearilide. Therefore, we were able to determine the true structure of eushearilide. Moreover, the synthetic compound was found to exhibit significant in vitro antifungal activity against various fungi and bacteria. PMID- 26814671 TI - Synthesis and structure-activity relationship study of FD-891: importance of the side chain and C8-C9 epoxide for cytotoxic activity against cancer cells. AB - Unified synthesis of FD-891 analogs and their structure-activity relationship are described. By using stereoselective allylation/crotylation and Evans aldol chemistry, six side-chain fragments having different length and terminus were synthesized. These fragments were coupled with a macrolactone fragment, improved synthesis of which was also developed here, to generate FD-891 and five truncated analogs. These synthetic compounds as well as three analogs obtained from fermentation of gene-disrupted Streptomyces graminofaciens mutants were tested for in vitro cytotoxic activity against HeLa cells. As a result, coexistence of the C8-C9 epoxide and side-chain terminus was found to be critical for the cytotoxic activity. PMID- 26814673 TI - A Cell-Penetrating Peptide with a Guanidinylethyl Amine Structure Directed to Gene Delivery. AB - A peptide composed of lysine with a guanidinylethyl (GEt) amine structure in the side chain [Lys(GEt)] was developed as a cell-penetrating peptide directed to plasmid DNA (pDNA) delivery. The GEt amine adopted a diprotonated form at neutral pH, which may have led to the more efficient cellular uptake of a Lys(GEt) peptide than an arginine-peptide at a low concentration. Lys(GEt)-peptide/pDNA complexes showed the highest transfection efficiency due to efficient endosomal escape without any cytotoxicity. Lys(GEt)-peptide may be a promising candidate as a gene delivery carrier. PMID- 26814674 TI - In vitro fibrinolysis and antithrombosis characterizations of novel recombinant microplasminogen with RGD and GPRP peptides. AB - Microplasminogen (MUPlg), a truncated form of human plasminogen, has considerable potential as a direct-acting thrombolytic agent. To further develop MUPlg into a thrombolytic agent with anti-thrombus properties, we constructed two MUPlg variants containing tripeptide Arg-Gly-Asp (RGD) and tetrapeptide Gly-Pro-Arg-Pro (GPRP) by site-directed mutagenesis. The recombinant cDNAs were expressed in yeast (Pichia pastoris) and purified to high homogeneity by Ni-NTA affinity chromatography. The specific activities of RGD-MUPlg and GPRP-MUPlg were 7.7 and 13.3 U/mg, respectively, as determined using the fibrin-plate method. RGD-MUPlg significantly inhibited ADP-induced platelet aggregation, which was 33.6- and 14.1-fold higher than the native MUPlg and GPRP-MUPlg, respectively. On the other hand, GPRP-MUPlg prolonged thrombin-initialized fibrinogen polymerization in a concentration-dependent manner, which was 9.2- and 5.7-fold stronger than MUPlg and RGD-MUPlg, respectively. Under activation by urokinase, MUPlg, RGD-MUPlg, and GPRP-MUPlg all showed over 80 % conversions to their active enzyme in 24 h. The structure models that docked RGD-MUPlg and MUPlg activation loops into the enzymatic active site of urokinase showed that Pro559 to Asp559 mutation of RGD MUPlg led to an alteration in the interaction, which possibly explains the slowed activation of RGD-MUPlg by urokinase over an 80-min period. In conclusion, this study has presented two recombinant MUPlg variants with anti-platelet aggregation and anti-fibrinogen clotting activity, thus suggesting the anti-thrombosis properties of these two MUPlg derivatives. PMID- 26814675 TI - Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test Data- The Influence of Different Parameters in a Routine Clinical Microbiology Laboratory. AB - INTRODUCTION: Many clinical microbiology laboratories report on cumulative antimicrobial susceptibility testing (cAST) data on a regular basis. Criteria for generation of cAST reports, however, are often obscure and inconsistent. Whereas the CLSI has published a guideline for analysis and presentation of cAST data, national guidelines directed at clinical microbiology laboratories are not available in Europe. Thus, we sought to describe the influence of different parameters in the process of cAST data analysis in the setting of a German routine clinical microbiology laboratory during 2 consecutive years. MATERIAL AND METHODS: We developed various program scripts to assess the consequences ensuing from different algorithms for calculation of cumulative antibiograms from the data collected in our clinical microbiology laboratory in 2013 and 2014. RESULTS: One of the most pronounced effects was caused by exclusion of screening cultures for multi-drug resistant organisms which decreased the MRSA rate in some cases to one third. Dependent on the handling of duplicate isolates, i.e. isolates of the same species recovered from successive cultures on the same patient during the time period analyzed, we recorded differences in resistance rates of up to 5 percentage points for S. aureus, E. coli and K. pneumoniae and up to 10 percentage points for P. aeruginosa. Stratification by site of care and specimen type, testing of antimicrobials selectively on resistant isolates, change of interpretation rules and analysis at genus level instead of species level resulted in further changes of calculated antimicrobial resistance rates. CONCLUSION: The choice of parameters for cAST data analysis may have a substantial influence on calculated antimicrobial resistance rates. Consequently, comparability of cAST reports from different clinical microbiology laboratories may be limited. We suggest that laboratories communicate the strategy used for cAST data analysis as long as national guidelines for standardized cAST data analysis and reporting do not exist in Europe. PMID- 26814676 TI - Hodgkin Lymphoma With Central Nervous System Disease at Primary Presentation. PMID- 26814677 TI - Preclinical Rheumatoid Arthritis: Progress Toward Prevention. PMID- 26814678 TI - Orchestrating the network of molecular pathways affecting aging: Role of nonselective autophagy and mitophagy. AB - Autophagy is best known as a mechanism involved in cellular recycling of biomolecules during periods of nutritional starvation. More recently, an additional function of autophagy emerged: the selective degradation of functionally impaired or surplus proteins, organelles and invading bacteria. With this function autophagy is integrated in a network of pathways involved in molecular and cellular quality control with a key impact on development and aging. Impairments in the autophagic machinery lead to accelerated aging and the development of diseases. Here we focus on the role of nonselective autophagy and mitophagy, the selective autophagic degradation of mitochondria, on aging and lifespan of biological systems. PMID- 26814680 TI - Identification of N-(6-mercaptohexyl)-3-(4-pyridyl)-1H-pyrazole-5-carboxamide and its disulfide prodrug as potent histone deacetylase inhibitors with in vitro and in vivo anti-tumor efficacy. AB - In this study, a collection of N-(6-mercaptohexyl)-3-substituted-1H-pyrazole-5 carboxamide HDAC inhibitors was developed. Among them, 15k was identified as the most potent inhibitor against total HDACs with IC50 of 0.008 MUM. Further isoenzyme assays revealed that 15k and its analogs have a preference for HDAC1-3 (class I) and HDAC6 (class IIb) isoforms. The enzyme-based potencies of 15k were 2- to 11-fold higher than those of Vorinostat. The disulfide prodrug 18 was found to be potent cytotoxic agent against a panel of seven tumor cells, causing hyper acetylation of histone and non-histone proteins in cellular level. In addition, 18 demonstrated a notable in vivo anti-tumor activity in HCT-116 xenografted model. This study provides further possibility of developing novel thiol-based HDAC inhibitors for the treatment of cancer. PMID- 26814681 TI - Medication Persistence of Disease-Modifying Antirheumatic Drugs and Anti-Tumor Necrosis Factor Agents in a Cohort of Patients With Rheumatoid Arthritis in Brazil. AB - OBJECTIVE: To assess the use and persistence of anti-tumor necrosis factor (anti TNF) versus disease-modifying antirheumatic drug (DMARD) therapies in patients with rheumatoid arthritis (RA) in Brazil. METHODS: This was a new-user cohort study of RA patients from 2003 to 2010, using administrative data. Individuals were classified as being persistent using a drug at the first year and the first 2 years after cohort entry, if they did not discontinue that drug during that period. Cox regression was used to identify potential determinants of discontinuation of therapy in each medication group. RESULTS: Among 76,351 patients, 14,313 were using anti-TNF (+/- DMARD) therapy. At the end of the first year of followup, 48.2% continued using anti-TNF (+/- DMARD) therapy compared to 42.6% who persisted with DMARDs only. At the end of the second year, 23.1% of anti-TNF (+/- DMARD) users and 19.3% of DMARD-only users continued with therapy. Infliximab users had the lowest persistence rates. Multivariate Cox regression analysis showed that among anti-TNF (+/- DMARD) users, higher discontinuation rates were observed in female patients, in patients with lower income (only at the first 2 years of followup), in nonresidents of the region with the highest Human Development Index (HDI) rates, in those with a higher comorbidity score, and in those enrolled in the 2003-2006 period. Among DMARD-only users, younger patients, patients with lower income, nonresidents in regions with high HDI, those with a higher comorbidity score, and those enrolled in the 2003-2006 period were also more likely to discontinue therapy. CONCLUSION: Brazilian patients with RA showed low rates of medication persistence for DMARDs and anti-TNF agents, particularly at the first 2 years of followup. Future work could determine what other factors might contribute to drug persistence in RA. PMID- 26814682 TI - Label-free and enzyme-free platform for the construction of advanced DNA logic devices based on the assembly of graphene oxide and DNA-templated AgNCs. AB - DNA-based molecular logic computation has drawn extensive attention in bioanalysis, intelligent diagnostics of diseases and other nanotechnology areas. Herein, taking 2-to-1 and 4-to-2 encoders and a 1-to-2 decoder as model molecular logic devices, we for the first time combined the quenching ability of GO (graphene oxide) to DNA-templated AgNCs with G-quadruplex-enhanced fluorescence intensity of porphyrin dyes for the construction of label-free and enzyme-free dual-output advanced DNA molecular logic devices. Also, through the application of negative logic conversion to an XOR logic gate and combined with an INHIBIT logic gate, we also operated a label-free and enzyme-free comparator. PMID- 26814683 TI - From Mononuclear to Dinuclear Iridium(III) Complex: Effective Tuning of the Optoelectronic Characteristics for Organic Light-Emitting Diodes. AB - Phosphorescent dinuclear iridium(III) complexes that can show high luminescent efficiencies and good electroluminescent abilities are very rare. In this paper, highly phosphorescent 2-phenylpyrimidine-based dinuclear iridium(III) complexes have been synthesized and fully characterized. Significant differences of the photophysical and electrochemical properties between the mono- and dinuclear complexes are observed. The theoretical calculation results show that the dinuclear complexes adopt a unique molecular orbital spatial distribution pattern, which plays the key role of determining their photophysical and electrochemical properties. More importantly, the solution-processed organic light-emitting diode (OLED) based on the new dinuclear iridium(III) complex achieves a peak external quantum efficiency (eta(ext)) of 14.4%, which is the highest eta(ext) for OLEDs using dinuclear iridium(III) complexes as emitters. Besides, the efficiencies of the OLED based on the dinuclear iridium(III) complex are much higher that those of the OLED based on the corresponding mononuclear iridium(III) complex. PMID- 26814684 TI - Intravital Imaging Study on Photodamage Produced by Femtosecond Near-infrared Laser Pulses In Vivo. AB - Ultrashort femtosecond pulsed lasers may provide indispensable benefits for medical bioimaging and diagnosis, particularly for noninvasive biopsy. However, the ability of femtosecond laser irradiation to produce biodamage in the living body is still a concern. To solve this biosafety issue, results of theoretical estimations as well as the in vitro and in situ experiments on femtosecond biodamage should be verified by experimental studies conducted in vivo. Here, we analyzed photodamage produced by femtosecond (19, 42 and 100 fs) near-infrared (NIR; ~800 nm) laser pulses with an average power of 5 and 15 mW in living undissected Drosophila larvae (in vivo). These experimental data on photodamage in vivo agree with the results of theoretical modeling of other groups. Femtosecond NIR laser pulses may affect the concentration of fluorescent biomolecules localized in mitochondria of the cells of living undissected Drosophila larva. Our findings confirm that the results of the mathematical models of femtosecond laser ionization process in living tissues may have a practical value for development of noninvasive biopsy based on the use of femtosecond pulses. PMID- 26814685 TI - Improving the postoperative handover process in the intensive care unit of a tertiary teaching hospital. AB - AIMS AND OBJECTIVES: The aim of this study was to improve the postoperative handover process and immediate postoperative patient outcomes. The objective was to implement a postoperative handover protocol in the neurosurgical intensive care unit of a tertiary teaching hospital. BACKGROUND: Postoperative handover is a multidisciplinary collaborative medical activity that involves information transfer, sequenced tasks and high-quality teamwork. Evidence suggests that a lack of a standardised postoperative handover protocol adversely influences care quality and potentially compromises patient safety. As there is a lack of such protocols in China, there is an identified need for improvement. DESIGN: This was a pretest/post-test study with follow-up after three months. METHODS: A postoperative handover protocol that included a postoperative handover checklist, a standardised handover pathway and core team member involvement was developed based on research evidence and expert opinions and was then implemented and evaluated. RESULTS: Following the implementation of this protocol, improved teamwork was achieved, surgeons were more frequently present at bedside handovers, the rate of transferring key messages increased, the rate of ventilator weaning within the first six hours of neurosurgical intensive care unit admission increased, and the ventilation duration per patient decreased without any clinical incident occurring in the first 24 hours after neurosurgical intensive care unit admission. CONCLUSIONS: Following the implementation of a tailored standardised handover protocol, communication, teamwork and short-term patient outcomes were improved. RELEVANCE TO CLINICAL PRACTICE: This clinically based research highlights the need for policy makers and administrators to create unit-specific protocols for improving postoperative handovers. PMID- 26814686 TI - Design and Rationale for the Endothelin-1 Receptor Antagonism in the Prevention of Microvascular Injury in Patients with non-ST Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention (ENDORA-PCI) Trial. AB - PURPOSE: Peri-procedural myocardial infarction (PMI) occurs in a small but significant portion of patients undergoing percutaneous intervention (PCI). The underlying mechanisms are complex and may include neurohormonal activation and release of vasoactive substances resulting in disruption of the coronary microcirculation. Endothelin in particular has been found in abundance in atherosclerotic plaques and in systemic circulation following PCI, and may be a potential culprit for PMI through its action on microvascular vasoconstriction, and platelet and neutrophil activation. In this study we aim to characterize the behavior of the coronary microcirculation during a PCI with the index of microvascular resistance (IMR) and the effect of peri-procedural endothelin antagonism. METHODS: The ENDORA-PCI trial is a randomized, double-blind, placebo controlled, single-center clinical trial designed to evaluate the efficacy of endothelin antagonism in attenuating the peri-procedural rise in IMR as a surrogate marker for PMI. The patients of interest are those with non-ST elevation acute coronary syndrome (NSTEACS) undergoing PCI, and we aim to recruit 52 patients overall to give the study a power of 80 % at an alpha level of 5 %. Patients will be randomized in a 1:1 fashion to either Ambrisentan, an endothelin antagonist, or placebo, prior to their PCI. IMR will be measured before and after PCI. The primary endpoint is the difference in peri-procedural changes in patients' IMR between the two groups. CONCLUSION: The ENDORA-PCI study will investigate whether endothelin antagonism with Ambrisentan attenuates the peri procedural rise in IMR in patients with NSTEACS undergoing PCI, and thus potentially the risk of PMI. PMID- 26814687 TI - [Oncologic Gynecology as the Area of Activity]. PMID- 26814688 TI - Estimation of Fetal Weight during Labor: Still a Challenge. AB - OBJECTIVE: To evaluate the accuracy of fetal weight prediction by ultrasonography labor employing a formula including the linear measurements of femur length (FL) and mid-thigh soft-tissue thickness (STT). METHODS: We conducted a prospective study involving singleton uncomplicated term pregnancies within 48 hours of delivery. Only pregnancies with a cephalic fetus admitted in the labor ward for elective cesarean section, induction of labor or spontaneous labor were included. We excluded all non-Caucasian women, the ones previously diagnosed with gestational diabetes and the ones with evidence of ruptured membranes. Fetal weight estimates were calculated using a previously proposed formula [estimated fetal weight = 1687.47 + (54.1 x FL) + (76.68 x STT). The relationship between actual birth weight and estimated fetal weight was analyzed using Pearson's correlation. The formula's performance was assessed by calculating the signed and absolute errors. Mean weight difference and signed percentage error were calculated for birth weight divided into three subgroups: < 3000 g; 3000-4000 g; and > 4000 g. RESULTS: We included for analysis 145 cases and found a significant, yet low, linear relationship between birth weight and estimated fetal weight (p < 0.001; R2 = 0.197) with an absolute mean error of 10.6%. The lowest mean percentage error (0.3%) corresponded to the subgroup with birth weight between 3000 g and 4000 g. CONCLUSIONS: This study demonstrates a poor correlation between actual birth weight and the estimated fetal weight using a formula based on femur length and mid-thigh soft-tissue thickness, both linear parameters. Although avoidance of circumferential ultrasound measurements might prove to be beneficial, it is still yet to be found a fetal estimation formula that can be both accurate and simple to perform. PMID- 26814689 TI - [Electronic Medical Record for Prenatal Care of Diabetic Women]. AB - OBJECTIVE: To present and validate a multifunctional electronic medical record (EMR) for outpatient care to women with endocrine disorders in pregnancy and to compare health information data fill rate to conventional medical records. METHODS: We developed an EMR named Ambulatory of Endocrine Diseases in Pregnancy (AMBEG) for systematic registration of health information The AMBEG was used for obstetric and endocrine care in a sample of pregnant women admitted to the maternity reference in high-risk pregnancies in Bahia from January 2010 to December 2013. We randomly selected 100 patients accompanied with AMBEG and 100 patients monitored with conventional consultation and compared the health information data fill rate of the electronic consultation to that performed using conventional medical records. RESULTS: 1461 consultations were held, of which 253, 963 and 245 were first, follow-up and puerperium consultations, respectively. Most patients were pregnant women with diabetes (77.2%) and 60.1% were women with pre-gestational diabetes. The AMBEG satisfactorily replaced the conventional medical record. The percentage of registered information was significantly higher in the AMBEG: clinical symptoms (87% versus 100, p < 0.01), uterine height (89 versus 75%, p = 0.01), total weight gain (91 versus 40%, p < 0.01) and specific diabetes data (diet, insulin regimen, glycemic control and management of hypoglycemia) revealed a significant difference (p < 0.01). The ability to export data to worksheets greatly facilitated and accelerated the statistical analysis of the data. CONCLUSIONS: AMBEG is a useful tool in clinical care for women with endocrine diseases during pregnancy. The fill rate of clinical information was superior to that registered in conventional medical records. PMID- 26814690 TI - [Correlation of the Levels of Fructosamine and Glycated Hemoglobin with the Blood Glucose Profile in Pregnant Women with Diabetes Mellitus]. AB - OBJECTIVE: To evaluate the correlation of the levels of fructosamine and of glycated hemoglobin (HbA1c) with the frequency of blood glucose self-monitoring values out of the treatment target range in pregnant women with diabetes mellitus. METHODS: We performed an observational, retrospective, cross-sectional study, including all pregnant women with diabetes who attended prenatal care visits at a tertiary teaching hospital during the year of 2014 and who presented at least 20 days of blood glucose self-monitoring prior to assessment of serum levels of fructosamine and HbA1c. Capillary blood glucose values out of the treatment target range were considered "hypoglycemia" when lower than 70 mg/dL and "hyperglycemia" when above the glycemic therapeutic target. We evaluated the correlation of the levels of fructosamine and of HbA1c with the frequencies of hyperglycemia and hypoglycemia recorded in the glucometer device by performing Tau-b of Kendall correlation tests. Next, linear regression tests were performed between the levels of HbA1c and of fructosamine and the frequencies of hypoglycemia and hyperglycemia. RESULTS: We included 158 pregnant women, from whom 266 blood samples were obtained for assessing fructosamine and HbA1c levels. Measurements of fructosamine and of HbA1c presented, respectively, Kendall's tau coefficient of 0.29 (p < 0.001) and 0.50 (p < 0.001) regarding the frequency of hyperglycemia, and of 0.09 (p = 0.046) and 0.25 (p < 0.001) regarding the frequency of hypoglycemia. In the linear regression model, levels of fructosamine and of HbA1c respectively presented determination coefficients R2 = 0.265 (p < 0.001) and R2 = 0.513 (p < 0.001) for the prediction of hyperglycemia, and R2 = 0.033 (p = 0.003) and R2 = 0.059 (p < 0.001) for the prediction of hypoglycemia. CONCLUSION: Levels of fructosamine and of HbA1c presented a weak to moderate correlation with the frequencies of hyperglycemia and hypoglycemia at blood glucose self-monitoring and were not able to accurately translate the deviations from the glycemic goals in pregnant women with diabetes. PMID- 26814691 TI - [Nutritional Status of Pregnant Women under Monitoring in Pre Distinct Prenatal Services: The Metropolitan Area and the Rural Environment]. AB - OBJECTIVE: To determine differences in some nutritional aspects of pregnant women assisted at prenatal care services in a country town and in a metropolitan area. METHODS: Pregnant women received prenatal care in the city of Belo Horizonte (BH), metropolitan area, and Paula Candido (PC), a country town. A Food Frequency Questionnaire (FFQ) containing socioeconomic information and information about eating habits was applied. In addition,weight and height were measured on the occasion of the visits and the women were ask to give their prepregnancy weight for subsequent BMI calculation. Data were analyzed according to region and trimester of pregnancy using the SPSS software version 15.0, the t-test to compare averages and the chi-square test of independence, with the level of significance set at 5%. RESULTS: 240 pregnant women were included, 90 from the country town and 150 from the metropolitan area. Of these, most were married (BH = 56.6%; PC = 46.6%) and did not work outside the home (BH = 54.0%; PC = 84.4%). They predominantly had 3-4 meals/ day during the 1st and 2nd quarters (BH = 54.0 and 46%; PC = 66.7 and 63.3%, respectively) and had 5-6 meals/day during Q3 in BH (44%). There was significant weight gain only in the 1st quarter (BH: 58,0%; PC: 53.3%). Weight gain versus eating habits was significant for the variables "lunch or dinner away from home" for the 1st quarter in BH (p = 0.006), "How many times they consume milk" in the 1 st quarter in PC (p = 0.03), and "How many times they consume junk food" in the 3rd quarter in BH (p = 0.009). CONCLUSIONS: Pregnant woman showed proper eating habits in both regions despite the prevalence of pregestational overweight in BH and a low level of education and income, especially in the country town, an indicator that may be unfavorable for the nutrition of pregnant women during this period. Studies of association between eating habits and newborn health will provide more information about nutrition during pregnancy. PMID- 26814692 TI - [Variability of Three-dimensional Automatic Ovarian Follicle Count in Menstrual Cycle]. AB - OBJECTIVE: To evaluate the variability of three-dimensional automatic counts of ovarian follicles measuring 2-6 to 2-10 mm during the menstrual cycle and to determine if this test can be applied outside the early follicular phase of the menstrual cycle. METHODS: in a prospective observational study, serial transvaginal ultrasound scans were performed from April 20, 2013, to October 30, 2014, on infertile patients. INCLUSION CRITERIA: age between 18 and 35 years, BMI 18-25 kg/m2, regular menstrual cycles, no history of ovarian surgery and no hormonal changes in TSH, prolactin, fasting insulin or glucose. We excluded patients with ovarian cysts or who did not complete one or more days of the serial transvaginal ultrasound scans. The follicle count was performed in 3D mode ultrasound with a Sono AVC system. Visits were scheduled for the early follicular, mid-follicular, periovulatory and luteal phases of the menstrual cycle. RESULTS: Forty-five women were included. The Friedman test showed that the total number of follicles measuring 2-6 mm varied significantly (p = 0.001) across the four periods of the menstrual cycle. The Paired Student t-test showed a significant increase in 2-6 mm follicle count from the mid-follicular and periovulatory phase to the luteal phase. We found no significant intra-cycle variation between the small follicles (2-6 mm) in the early follicular, mid follicular and periovulatory phases. The Friedman test showed that the total number of follicles measuring 2-10 mm varied significantly (p = 0.003) across the menstrual cycle. CONCLUSIONS: The variation of three-dimensional automatic counts of 2-6 mm follicles in the early follicular, mid-follicular and periovulatory phases was not statistically significant. The significant variability in the counts of follicles measuring 2-10 mm across the menstrual cycle does not permit this examination to be performed side the early follicular phase. PMID- 26814693 TI - Comparison of Classical and Secondary Cytologic Criteria Relative to Hybrid Capture for Diagnosing Cervical-vaginal Infection by Human Papillomavirus. AB - OBJECTIVE: To compare the diagnostic accuracy of the classic Meisels cytologic criteria and the Schneider secondary criteria relative to the hybrid capture method for diagnosing HPV infection. METHODS: This was a retrospective study performed at a public university hospital. A total of 41 patients with a cytologic diagnosis of HPV infection and 40 HPV-negative patients were selected for review of the cervical-vaginal smears seeking to classical and secondary criteria. A single pathologist reviewed the slides in search of the criteria. The classical and secondary cytologic criteria were compared with the hybrid capture for diagnosing HPV infection. Bartleti test was applied for the age analysis, and Fisher's exact test was used to compare proportions. The tests were considered significant when the probability of rejecting the null hypothesis was less than 5% (p < 0.05). RESULTS: The Meisels criteria were less sensitive (34.0%) than the secondary Schneider criteria (57.5%) when compared with the hybrid capture (p < 0.0001), although the specificity of the former criteria was non-significantly higher (91.2% and 67.7%, respectively). In cases of moderate or intense inflammation, the sensitivity and specificity of the Schneider criteria were decreased, 33.3% and 50.0% respectively (p = 0.0115). CONCLUSIONS: Compared with hybrid capture for diagnosis of HPV infection, the sensitivity of the secondary Schneider criteria was higher than the classical Meisels criteria.Moderate or intense inflammation reduces the sensitivity and specificity of the secondary Schneider criteria for diagnosing HPV infection using the hybrid capture as the gold standard. PMID- 26814694 TI - The Influence of Education and Depression on Autonomy of Women with Chronic Pelvic Pain: A Cross-sectional Study. AB - OBJECTIVE: Patient autonomy has great importance for a valid informed consent in clinical practice. Our objectives were to quantify the domains of patient autonomy and to evaluate the variables that can affect patient autonomy in women with chronic pelvic pain. METHODS: This study is a cross sectional survey performed in a tertiary care University Hospital. Fifty-two consecutive women scheduled for laparoscopic management of chronic pelvic were included. Three major components of autonomy (competence, information or freedom) were evaluated using a Likert scale with 24 validated affirmatives. RESULTS: Competence scores (0.85 vs 0.92; p = 0.006) and information scores (0.90 vs 0.93; p = 0.02) were low for women with less than eight years of school attendance. Information scores were low in the presence of anxiety (0.91 vs 0.93; p = 0.05) or depression (0.90 vs 0.93; p = 0.01). CONCLUSIONS: Our data show that systematic evaluation of patient autonomy can provide clinical relevant information in gynecology. Low educational level, anxiety and depression might reduce the patient autonomy in women with chronic pelvic pain. PMID- 26814696 TI - Familism, Social Network Characteristics, and Well-being among Older Adults in Mexico. AB - Familism, is a cultural value considered to be central to Mexican culture. Older generations are thought to more strongly adhere to familistic values; however, little is known about the implications of familism in late-life. The goal of the current study was to examine links between familism, social network characteristics, and well-being among Mexican older adults. A sample of 556 older adults (50-99 years old) was drawn from the Study of Social Relations and Well being in Mexico. Various aspects of social network characteristics and familism varied by age, gender, and education status. Familism was correlated with contact frequency and geographic proximity, but not proportion of family in network. Regression analyses indicated higher familism was associated with better psychological and physical well-being, yet familism interacted with proportion of family to predict both self-rated health and chronic conditions indicating that a discrepancy between familistic values and actual family support may be detrimental for older Mexicans' physical health. The discussion highlights the complex interrelationships and potential protective effects of familism. Future research should continue to examine the implications of familism and family relationships in the Mexican context; in particular, how generational shifts in familism influence intergenerational relations and well-being. PMID- 26814697 TI - A versatile proximity-dependent probe based on light-up DNA-scaffolded silver nanoclusters. AB - It is well-known that proximity-dependent probes containing an analyte recognization site and a signal formation domain could be assembled specifically into a sandwich-like structure (probe-analyte-probe) via introducing an analyte. In this work, using the design for zirconium ion (Zr(4+)) detection as the model, we develop a novel and reliable proximity-dependent DNA-scaffolded silver nanocluster (DNA/AgNC) probe for Zr(4+) detection via target-induced emitter proximity. The proposed strategy undergoes the two following processes: target mediated emitter pair proximity as target recognition implement and the synthesis of DNA/AgNCs with fluorescence as a signal reporter. Upon combination of the rationally designed probe with Zr(4+), the intact templates were obtained according to the -PO3(2-)-Zr(4+)-PO3(2-)- pattern. The resultant structure with an emitter pair serves as a potent template to achieve highly fluorescent DNA/AgNCs. To verify the universality of the proposed proximity-dependent DNA/AgNC probe, we extend the application of the proximity-dependent probe to DNA and adenosine triphosphate (ATP) detection by virtue of a specific DNA complementary sequence and ATP aptamer as a recognition unit, respectively. The produced fluorescence enhancement of the DNA/AgNCs in response to the analyte concentration allows a quantitative evaluation of the target, including Zr(4+), DNA, and ATP with detection limits of ~3.00 MUM, ~9.83 nM, and ~0.81 mM, respectively. The proposed probe possesses good performance with simple operation, cost-effectiveness, good selectivity, and without separation procedures. PMID- 26814699 TI - Metabolic crisis occurs with seizures and periodic discharges after brain trauma. AB - OBJECTIVE: Traumatic brain injury (TBI) results in persistent disruption of brain metabolism that has yet to be mechanistically defined. Early post-traumatic seizures are one potential mechanism for metabolic crisis and hence could be a therapeutic target. We hypothesized that seizures and pseudoperiodic discharges (PDs) may be mechanistically linked to metabolic crisis as measured by cerebral microdialysis. METHODS: A prospective multicenter study of surface and intracortical depth electroencephalography (EEG) was performed in conjunction with cerebral microdialysis in a cohort of severe TBI patients with time-locked analysis of the neurochemical response to seizures and pseudoperiodic discharges. RESULTS: Seizures or PDs occurred in 61% of 34 subjects, with 42.9% of these seizures noted only on intracortical depth EEG and in some cases lasting for many hours. Metabolic crisis as measured by elevated cerebral microdialysis lactate/pyruvate ratio occurred during seizures or PDs but not during electrically nonepileptic epochs. INTERPRETATION: In TBI patients, seizures and periodic discharges are one mechanism for metabolic crisis, and hence represent a therapeutic target for future study. PMID- 26814700 TI - Antioxidant activity evaluation and HPLC-photodiode array/MS polyphenols analysis of pomegranate juice from selected italian cultivars: A comparative study. AB - Chemical composition of pomegranate juice can vary due to cultivar, area of cultivation, ripening, climate, and other variables. This study investigates the polyphenolic composition and antioxidant activity of juices obtained from six old Italian pomegranate cultivars. Fruit accessions physicochemical characteristics were determined. Total polyphenols content (TPC), anthocyanin content (TAC) and proanthocyanidin content (TPAC) were measured in the juice samples. Phenolic bioactive molecules were analyzed by HPLC-photodiode array (PDA)/ESI-MS in all the pomegranate juices. In total, seven nonanthocyanidinic and six anthocyanidinic compounds were identified. The six anthocyanins were found in all juices although at different amounts. These results were correlated with antioxidant activity measured by three different chemical assays: 2,2 diphenyl-1 picrylhydrazyl (DPPH(*) ) scavenging activity assay, Trolox equivalent antioxidant capacity (TEAC) method and ferric reducing-antioxidant power (FRAP) assay. Pomegranate juices obtained by six different varieties show variable polyphenolic content and antioxidant activity. The antioxidant capacity methods used have shown variable sensitivity, supporting the hypothesis that different methods for the assessment of antioxidant capacity of food compounds are indeed necessary, due to complexity of sample composition and assay chemical mechanism and sensitivity. Juices from Italian pomegranate show good levels of polyphenols content and antioxidant activity making them potential candidates for employment in the food industry. PMID- 26814701 TI - Atypical early histories predict lower extraversion in captive chimpanzees. AB - Although much research has been conducted to understand personality development in humans, there remain substantial gaps in our understanding of these processes, particularly in relation to social influences. As such, investigations into personality development in our closest living relative, the chimpanzee, may provide useful insight. We evaluated the impact of early social exposure (to both humans and conspecifics) on personality development by studying 88 chimpanzees, including former pets and entertainers, living in accredited zoos and sanctuaries. During infancy, subjects varied in the amount of time spent with conspecifics compared with humans. Caregivers familiar with the chimpanzees rated them using a modified version of the Hominoid Personality Questionnaire (HPQ) and the ratings were found to have strong inter-rater reliability. We used the published structure of the HPQ to evaluate our results in relation to differences in early life experience. Chimpanzees who as infants spent less time with conspecifics were rated as lower in Extraversion later in life in comparison with chimpanzees who as infants spent more time with conspecifics. These results suggest that a broad range of social influences should be considered when evaluating the impact of early social environment on later personality expression. PMID- 26814703 TI - Adsorption of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) on a soil organic matter. A DFT M05 computational study. AB - Adsorption of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) by soil organic matter considering the Leonardite Humic Acid (LHA) model at the M05/tzvp level of Density Functional Theory (DFT) applying cluster approximation has been investigated. Different orientations of CL-20 toward LHA surface were examined. It was found that deprotonation of LHA is required to obtain stable complexes with CL-20. Hydrogen bonds between CL-20 and deprotonated LHA were analyzed applying the atoms in molecules (AIM) theory. An attachment or removal of an electron with respect to the complex does not have significant effect on mutual orientation of the adsorbent in complexes. It was shown that adsorbed CL 20 does not undergo redox transformation and, therefore, adsorption on soil organic matter may be responsible for decrease of the degradation rate of CL-20 in soil. PMID- 26814702 TI - Epigenetic regulation of hematopoiesis by DNA methylation. AB - During embryonic development, cell type-specific transcription factors promote cell identities, while epigenetic modifications are thought to contribute to maintain these cell fates. Our understanding of how genetic and epigenetic modes of regulation work together to establish and maintain cellular identity is still limited, however. Here, we show that DNA methyltransferase 3bb.1 (dnmt3bb.1) is essential for maintenance of hematopoietic stem and progenitor cell (HSPC) fate as part of an early Notch-runx1-cmyb HSPC specification pathway in the zebrafish. Dnmt3bb.1 is expressed in HSPC downstream from Notch1 and runx1, and loss of Dnmt3bb.1 activity leads to reduced cmyb locus methylation, reduced cmyb expression, and gradual reduction in HSPCs. Ectopic overexpression of dnmt3bb.1 in non-hematopoietic cells is sufficient to methylate the cmyb locus, promote cmyb expression, and promote hematopoietic development. Our results reveal an epigenetic mechanism supporting the maintenance of hematopoietic cell fate via DNA methylation-mediated perdurance of a key transcription factor in HSPCs. PMID- 26814704 TI - Potential use of edible crops in the phytoremediation of endosulfan residues in soil. AB - Endosulfan is a persistent and toxic organochlorine pesticide of banned or restricted use in several countries. It has been found in soil, water, and air and is bioaccumulated and magnified in ecosystems. Phytoremediation is a technology that promises effective and inexpensive cleanup of contaminated hazardous sites. The potential use of tomato, sunflower, soybean and alfalfa species to remove endosulfan from soil was investigated. All species were seeded and grown in endosulfan-spiked soils (8000 ng g(-1) dry weight) for 15 and 60 days. The phytoremediation potential was evaluated by studying the endosulfan levels and distribution in the soil-plant system, including the evaluation of soil dehydrogenase activity and toxic effects on plants. Plant endosulfan uptake leads to lower insecticide levels in the rhizosphere with regards to bulk soil or near root soil at 15 days of growth. Furthermore, plant growth-induced physical chemical changes in soil were evidenced by differences in soil dehydrogenase activity and endosulfan metabolism. Sunflower showed differences in the uptake and distribution of endosulfan with regard to the other species, with a distribution pesticide pattern of aerial tissues > roots at 15 days of growth. Moreover, at 60 days, sunflower presented the highest pesticide levels in roots and leaves along with the highest phytoextraction capacity. Lipid peroxidation levels correlated positively with endosulfan accumulation, reflecting the negative effect of this insecticide on plant tissues. Considering biomass production and accumulation potential, in conjunction with the reduction of soil pesticide levels, sunflower plants seem to be the best phytoremediation candidate for endosulfan residues in soils. PMID- 26814705 TI - Low doses of nanodiamonds and silica nanoparticles have beneficial hormetic effects in normal human skin fibroblasts in culture. AB - Nanodiamonds (ND) and silica nanoparticles (SiO2-NP) have been much investigated for their toxicity at high doses, little is known about their biological activity at low concentrations. Here we report the biphasic dose response of ND and SiO2 NP in modulating normal human facial skin fibroblasts (FSF1) in culture. ND and SiO2-NP at low concentration (up to 0.5 MUg/ml) had beneficial effects on FSF1 in terms of increasing their proliferation and metabolic activity. Exposure of FSF1 cells to low levels of NP enhanced their wound healing ability in vitro and slowed down aging during serial passaging as measured by maintenance of youthful morphology, reduction in the rate of loss of telomeres, and the over all proliferative characteristics. Furthermore, NP treatment induced the activation of Nrf2- and FOXO3A-mediated cellular stress responses, including an increased expression of heme oxygenease (HO-1), sirtuin (SIRT1), and DNA methyltransferase II (DNMT2). These results imply that ND and SiO2-NP at low doses are potential hormetins, which exert mild stress-induced beneficial hormetic effects through improved survival, longevity, maintenance, repair and function of human cells. PMID- 26814706 TI - SlyA regulates phytotoxin production and virulence in Dickeya zeae EC1. AB - Dickeya zeae is a causal agent of rice root rot disease. The pathogen is known to produce a range of virulence factors, including phytotoxic zeamines and extracellular enzymes, but the mechanisms of virulence regulation remain vague. In this study, we identified a SlyA/MarR family transcription factor SlyA in D. zeae strain EC1. Disruption of slyA significantly decreased zeamine production, enhanced swimming and swarming motility, reduced biofilm formation and significantly decreased pathogenicity on rice. Quantitative polymerase chain reaction (qPCR) analysis confirmed the role of SlyA in transcriptional modulation of a range of genes associated with bacterial virulence. In trans expression of slyA in expI mutants recovered the phenotypes of motility and biofilm formation, suggesting that SlyA is downstream of the acylhomoserine lactone-mediated quorum sensing pathway. Taken together, the findings from this study unveil a key transcriptional regulatory factor involved in the modulation of virulence factor production and overall pathogenicity of D. zeae EC1. PMID- 26814707 TI - Comparison of different platelet transfusion thresholds prior to insertion of central lines in patients with thrombocytopenia. AB - This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of different platelet transfusion thresholds prior to the insertion of a central line in patients with thrombocytopenia (low platelet count). PMID- 26814709 TI - The pterygopalatine recess of the superior nasal meatus. AB - The pneumatizations surrounding the pterygopalatine fossa (PPF) and closely related to the sphenopalatine foramen are anatomically variable. During the assessment of a cone beam computed tomography of a 64-year-old male patient, we found bilaterally a previously unreported anatomic variant. This was represented by a lateral or pterygopalatine recess (PPR) of the superior nasal meatus which extended in the anterior wall of the PPF and protruded within the maxillary sinus to determine a maxillary bulla. The PPR was antero-superior to the sphenopalatine foramen. Additionally were found a right nasal septal deviation, seemingly compensated by a left middle concha bullosa and a left prominent ethmoidal bulla. The superior turbinates were also pneumatized. Such anatomic variants related to the pterygopalatine angle of the maxillary sinus should be explored prior to surgical or endoscopic procedures which target the maxillary sinus, the pterygopalatine fossa, or the skull base. PMID- 26814708 TI - Effects of Complement C4 Gene Copy Number Variations, Size Dichotomy, and C4A Deficiency on Genetic Risk and Clinical Presentation of Systemic Lupus Erythematosus in East Asian Populations. AB - OBJECTIVE: Human complement C4 is complex, with multiple layers of diversity. The aims of this study were to elucidate the copy number variations (CNVs) of C4A and C4B in relation to disease risk in systemic lupus erythematosus (SLE), and to compare the basis of race-specific C4A deficiency between East Asians and individuals of European descent. METHODS: The East Asian study population included 999 SLE patients and 1,347 healthy subjects. Variations in gene copy numbers (GCNs) of total C4, C4A, and C4B, as well as C4-Long and C4-Short genes, were determined and validated using independent genotyping technologies. Genomic regions with C4B96 were investigated to determine the basis of the most basic C4B protein occurring concurrently with C4A deficiency. RESULTS: In East Asians, high GCNs of total C4 and C4A were strongly protective against SLE, whereas low and medium GCNs of total C4 and C4A, and the absence of C4-Short genes, were risk factors for SLE. Homozygous C4A deficiency was infrequent in East Asian subjects, but had an odds ratio (OR) of 12.4 (P = 0.0015) for SLE disease susceptibility. Low serum complement levels were strongly associated with low GCNs of total C4 (OR 3.19, P = 7.3 * 10(-7) ) and C4B (OR 2.53, P = 2.5 * 10(-5) ). Patients with low serum complement levels had high frequencies of anti-double-stranded DNA antibodies (OR 4.96, P = 9.7 * 10(-17) ), hemolytic anemia (OR 3.89, P = 3.6 * 10(-10) ), and renal disease (OR 2.18, P = 8.5 * 10(-6) ). The monomodular-Short haplotype found to be prevalent in European Americans with C4A deficiency, which was in linkage disequilibrium with HLA-DRB1*0301, was scarce in East Asians. Instead, most East Asian subjects with C4A deficiency were found to have a recombinant haplotype with bimodular C4-Long and C4-Short genes, encoding C4B1 and C4B96, which was linked to HLA-DRB1*1501. DNA sequencing revealed an E920K polymorphism in C4B96. CONCLUSION: C4 CNVs and deficiency of C4A both play an important role in the risk and manifestations of SLE in East Asian and European populations. PMID- 26814710 TI - Correction to PEGylated Silk Nanoparticles for Anticancer Drug Delivery. PMID- 26814711 TI - Gene-expression profiling of localized prostate cancer: still miles to go before we sleep. PMID- 26814712 TI - High expression of matrix metalloproteinases: MMP-2 and MMP-9 predicts poor survival outcome in colorectal carcinoma. AB - AIM: To evaluate the expression pattern of matrix metalloproteinases (MMPs); MMP 2, MMP-7 and MMP-9 in colorectal cancer (CRC) and determine its prognostic potential. PATIENTS & METHODS: CRC samples of 127 patients were studied. Protein expressions of MMP-2, -7 and -9 were analyzed by immunohistochemistry and association with clinicopathological variables was statistically analyzed. RESULTS: Overexpressions of MMP-2 and MMP-9 correlated with poor outcome as evaluated by univariate Kaplan-Meier for disease-free survival (p = 0.04, p = 0.0001) and disease-specific survival (p = 0.01, p = 0.01), respectively. Cox analysis of MMP-2 and -9 were significant independent predictors of disease-free survival (p = 0.006, p = 0.018) and disease-specific survival (p = 0.004, p = 0.049), respectively. CONCLUSION: MMPs expression patterns provide useful prognostic information in CRC, while predicting the patients at high risk for recurrent disease. PMID- 26814713 TI - Multiple Exposures to Ascaris suum Induce Tissue Injury and Mixed Th2/Th17 Immune Response in Mice. AB - Ascaris spp. infection affects 800 million people worldwide, and half of the world population is currently at risk of infection. Recurrent reinfection in humans is mostly due to the simplicity of the parasite life cycle, but the impact of multiple exposures to the biology of the infection and the consequences to the host's homeostasis are poorly understood. In this context, single and multiple exposures in mice were performed in order to characterize the parasitological, histopathological, tissue functional and immunological aspects of experimental larval ascariasis. The most important findings revealed that reinfected mice presented a significant reduction of parasite burden in the lung and an increase in the cellularity in the bronchoalveolar lavage (BAL) associated with a robust granulocytic pulmonary inflammation, leading to a severe impairment of respiratory function. Moreover, the multiple exposures to Ascaris elicited an increased number of circulating inflammatory cells as well as production of higher levels of systemic cytokines, mainly IL-4, IL-5, IL-6, IL-10, IL-17A and TNF-alpha when compared to single-infected animals. Taken together, our results suggest the intense pulmonary inflammation associated with a polarized systemic Th2/Th17 immune response are crucial to control larval migration after multiple exposures to Ascaris. PMID- 26814714 TI - Osteoinductive potential of 4 commonly employed bone grafts. AB - OBJECTIVES: Guided bone regeneration (GBR) aims to predictably restore missing bone that has been lost due to trauma, periodontal disease or a variety of systemic conditions. Critical to this procedure is the ability of a bone grafting material to predictably serve as a 3-dimensional scaffold capable of inducing cell and bone tissue in-growth at the material surface. Although all bone grafts are osteoconductive to bone-forming osteoblasts, only a small number of commercially available bone grafts with FDA approval are osteoinductive including demineralized freeze-dried bone allographs (DFDBA) and scaffolds containing bone morphogenetic proteins (BMPs). Recently, a class of synthetic bone grafts fabricated from biphasic calcium phosphate (BCP) sintered at a low temperature have been shown to form ectopic bone formation in non-skeletal sites without the use of growth factors. Therefore, the present study aimed to compare the osteoinductive potential of this group of synthetic BCP alloplasts with autografts, allografts and xenografts. MATERIALS AND METHODS: In the present study, 4 types of bone grafting materials including autogenous bone harvested with a bone mill, DFDBA (LifeNet, USA), a xenograft derived from bovine bone mineral (NBM, BioOss, Geistlich, Switzerland) and a novel synthetic biphasic calcium phosphate (BCP, Straumman, Switzerland) were implanted into intramuscular pouches of 24 rats and analysed histologically for their ability to form ectopic bone formation around grafting particles. A semi-quantitative osteoinductive score was used to quantify the osteoinductive ability of each bone graft. RESULTS: The results from the present study reveal that (1) autogenous bone resorbed rapidly in vivo, (2) the xenograft showed no potential to form ectopic bone formation and (3) both DFDBA and BCP were able to stimulate ectopic bone formation. CONCLUSION: These studies demonstrate that these newly developed synthetic bone grafts have potential for inducing ectopic bone formation similar to DFDBA. Future clinical testing is necessary to reveal their bone-inducing properties in clinical scenarios including GBR procedures and in combination with implant dentistry. CLINICAL RELEVANCE: Novel BCP scaffolds are able to induce ectopic bone formation without the use of osteoinductive growth factors such as BMP2 and thus demonstrate a large clinical possibility to further enhance bone formation for a variety of clinical procedures. PMID- 26814715 TI - Patient morbidity and root coverage outcomes after the application of a subepithelial connective tissue graft in combination with a coronally advanced flap or via a tunneling technique: a randomized controlled clinical trial. AB - BACKGROUND AND OBJECTIVE: Subepithelial connective tissue grafts (SeCTG) in conjunction with a coronally advanced flap (CAF) or with tunneling technique (TT) are common periodontal procedures with similar indications for the treatment of a denuded root surface; however, it is unclear whether patient discomfort and postoperative morbidity are comparable in both approaches. The aim of this randomized controlled clinical trial was to compare the patient morbidity and root coverage outcomes of a SeCTG used in combination with a CAF or TT. MATERIALS AND METHODS: For this single-center, randomized, clinical trial, patients were randomly assigned to receive SeCTG + CAF (control group) or SeCTG + TT (test group). Postoperative questionnaires at 3 days post intervention were administered to evaluate postoperative discomfort, bleeding, and inability to masticate. Evaluation of patients' perception of pain was performed using a visual analog scale (VAS). Clinical outcomes including percentage of root coverage (RC) and complete root coverage (CRC) were recorded 12 months postoperatively. RESULTS: Fifty patients (25 SeCTG + CAF and 25 SeCTG + TT) completed the study. Healing was uneventful for all test and control patients. The SeCTG + TT group showed a longer chair time (33.6 (3.6) and 23.6 (4.2) min for the SeCTG + TT and the SeCTG + CAF, respectively), as well as more painkiller consumption: 2736 vs. 1536 mg (p < 0.001). At the same time, the SeCTG + CAF group reported less pain or discomfort in all four sections of the questionnaire: pain experienced within the mouth as a whole, pain experienced throughout the day, pain experienced at night, and edema experienced after the surgery (p = 0.002, p = 0.001, p = 0.001, and p = 0001, respectively). Both treatments showed clinical efficacy in terms of root coverage as no differences per group were observed in the percentage of root coverage (87 vs. 85 %, p = 704) or patients with complete root coverage (60 vs. 52 %, p = 0.569). CONCLUSIONS: SeCTG + TT is associated with a greater incidence of pain and discomfort compared to SeCTG + CAF in early postoperative periods, as well as a longer chair time. Both treatments showed similar clinical efficacy in terms of root coverage. CLINICAL RELEVANCE: The results of this study may influence the surgeon's choice on which root coverage procedure should be performed considering the need of more chair time and more painkiller assumption with the tunneling technique. PMID- 26814716 TI - Risk factors for delayed gastric emptying following distal pancreatectomy. AB - PURPOSE: Delayed gastric emptying (DGE) is a frequent complication after pancreatoduodenectomy and other types of upper gastrointestinal surgery with published incidences as high as 60 %. The present study examines the incidence of DGE following distal pancreatic resection (DPR). METHODS: Between 2002 and 2014, 100 patients underwent conventional DPR at our department. DGE was classified according to the 2007 International Study Group of Pancreatic Surgery definition. Patients were analyzed regarding severity of DGE, morbidity and mortality, length of hospital stay, and demographic factors. RESULTS: Overall incidence of DGE was 24 %. No difference in age, gender, or other demographic factors was observed in patients with DGE. Perioperative characteristics (splenectomy rate, closure technique of the pancreatic remnant, operation time, blood loss and transfusion, ICU, ASA score) were comparable. Major complications were associated with DGE (11/24 patients (46 %) vs. 19/76 patients (25 %) without DGE) and the rate of pancreatic fistula was significantly higher in the group of patients with DGE (14/24 patients (58 %) vs. 27/76 patients (36 %), P = 0.047). In multivariate analysis, a periampullary malignancy was shown to be a significant factor for DGE development. DGE significantly prolonged hospital stay (14 vs. 22 days). CONCLUSIONS: DGE is a substantial complication not only after pancreatoduodenectomy, but it also occurs frequently after DPR. Prevention of pancreatic fistula might reduce its incidence, especially in patients with malign pathology. PMID- 26814717 TI - The Elevated Secreted Immunoglobulin D Enhanced the Activation of Peripheral Blood Mononuclear Cells in Rheumatoid Arthritis. AB - Immunoglobulin D (IgD) is a surface immunoglobulin that is expressed as either membrane IgD (mIgD) or secreted IgD (sIgD). Researchers have shown that sIgD is often elevated in patients with autoimmune diseases. The possible roles of sIgD on the function of peripheral blood mononuclear cells (PBMCs) in rheumatoid arthritis (RA) are still unclear. In this study, we compared the expression of sIgD, mIgD and IgD receptor (IgDR) in RA patients and healthy controls, and investigated the effect of sIgD on the function of PBMCs. We found that the levels of sIgD, mIgD and IgDR were significantly higher in RA patients compared with healthy controls. The concentrations of sIgD were positively correlated with soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), rheumatoid factor (RF) and C-reactive protein (CRP) in RA patients. Strikingly, IgD could enhance the proliferation of PBMCs and induce IL-1alpha, IL-1beta, TNF-alpha, IL 6 and IL-10 production from PBMCs. Moreover, the percentage of activated T cell subsets (CD4+CD69+, CD4+CD154+) and activated B cell subsets (CD19+CD23+, CD19+CD21+, CD19+IgD+ and CD19-CD138+) were increased by IgD. The percentage of unactivated T cell subset (CD4+CD62L+) and immature B cell subset (CD19+IgM+IgD-) were decreased by IgD in PBMCs. Furthermore, the expressions of IgDR on T and B cells were significantly increased by treatment with IgD. Our results demonstrate that IgD enhanced the activation of PBMCs, which may contribute to RA pathogenesis. Therefore, IgD could be a potential novel immunotherapeutic target for the management of RA. PMID- 26814718 TI - JadX is a Disparate Natural Product Binding Protein. AB - We report that JadX, a protein of previously undetermined function coded for in the jadomycin biosynthetic gene cluster of Streptomyces venezuelae ISP5230, affects both chloramphenicol and jadomycin production levels in blocked mutants. Characterization of recombinant JadX through protein-ligand interactions by chemical shift perturbation and WaterLOGSY NMR spectroscopy resulted in the observation of binding between JadX and a series of jadomycins and between JadX and chloramphenicol, another natural product produced by S. venezuelae ISP5230. These results suggest JadX to be an unusual class of natural product binding protein involved in binding structurally disparate natural products. The ability for JadX to bind two different natural products in vitro and the ability to affect production of these secondary metabolites in vivo suggest a potential role in regulation or signaling. This is the first example of functional characterization of these JadX-like proteins, and provides insight into a previously unobserved regulatory process. PMID- 26814719 TI - Transdermal Diagnosis of Malaria Using Vapor Nanobubbles. PMID- 26814720 TI - Chronic obstructive pulmonary disease comorbidities. AB - PURPOSE OF REVIEW: Classic descriptions of chronic obstructive pulmonary disease (COPD) centered on its impact on respiratory function. It is currently recognized that comorbidities contribute to the severity of symptoms and COPD progression. Understanding COPD-comorbidities associations could provide innovative treatment strategies and identify new mechanistic pathways to be targeted. RECENT FINDINGS: Some comorbidities are clustered with specific COPD phenotypes. There are stronger associations between airway-predominant disease and cardio-metabolic comorbidities, whereas in emphysema-predominant COPD sarcopenia and osteoporosis are frequent. These patterns suggest different inflammatory pathways acting by COPD phenotype. Osteoporosis is a major concern in COPD, particularly among men. Although beta-blockers use for cardiac indications in COPD remains low, recent evidence suggests that this medication group could decrease COPD exacerbations. Gastroesophageal reflux is consistently associated with poor COPD outcomes, but mechanisms and impact of treatment are still unclear. Nontraditional comorbid conditions, such as cognitive impairment, anxiety, and depression have significant impact in COPD outcomes. SUMMARY: Clinicians should screen their COPD patients for the presence of cardiovascular disease, diabetes, osteoporosis, sleep apnea, and sarcopenia, comorbidities for which specific treatments are available and associated with better COPD outcomes. The impact of interventions to treat gastroesophageal reflux disease, anxiety and depression is still to be defined. PMID- 26814721 TI - An update on pharmacologic management of chronic obstructive pulmonary disease. AB - PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is a widespread disease process with important clinical and economic implications. This review will summarize new pharmacotherapy for the treatment of COPD. RECENT FINDINGS: Several recent clinical trials have led to the approval of new inhaler therapies for COPD. Many of these are specifically targeting combination long-acting beta agonists and long-acting muscarinic antagonists for late stage COPD. SUMMARY: Several new bronchodilators are available on the market, especially in combination form. The new drug combinations have positive data though clinical relevance, and comparisons to available and well established therapies are still needed. Specifically, translating improved forced expiratory volume into meaningful clinical outcomes remains challenging. PMID- 26814722 TI - Biomass smoke exposure and chronic lung disease. AB - PURPOSE OF REVIEW: Approximately 3 billion people worldwide rely on coal and biomass fuel for cooking and heating. Biomass smoke exposure is associated with several chronic lung diseases, including chronic obstructive pulmonary disease (COPD), asthma-COPD overlap syndrome, usual interstitial pneumonitis, hut lung, and bronchial anthracofibrosis. Household air pollution primarily from biomass smoke is the biggest risk factor for COPD worldwide. Despite the significant burden of biomass smoke-related respiratory disease, the exposure is still underappreciated worldwide, especially in high-income countries. RECENT FINDINGS: Recent literature highlights the immunoinflammatory differences between biomass smoke-related COPD and tobacco smoke-related COPD that may lead to better understanding of the differences in the clinical phenotypes between the two entities, suggests an association with the recently recognized asthma-COPD overlap syndrome, and elucidates the burden of disease in high-income countries. SUMMARY: The current review focuses on the association between biomass smoke and common chronic respiratory diseases, discuss differences between biomass smoke related COPD and tobacco smoke-related COPD, highlights chronic respiratory diseases that are specific for biomass smoke exposure such as hut lung and bronchial anthracofibrosis, and discusses the known impact of beneficial interventions. PMID- 26814723 TI - Study of Disease Progression and Relevant Risk Factors in Diabetic Foot Patients Using a Multistate Continuous-Time Markov Chain Model. AB - The diabetic foot is a lifelong disease. The longer patients with diabetes and foot ulcers are observed, the higher the likelihood that they will develop comorbidities that adversely influence ulcer recurrence, amputation and survival (for example peripheral arterial disease, renal failure or ischaemic heart disease). The purpose of our study was to quantify person and limb-related disease progression and the time-dependent influence of any associated factors (present at baseline or appearing during observation) based on which effective prevention and/or treatment strategies could be developed. Using a nine-state continuous-time Markov chain model with time-dependent risk factors, all living patients were divided into eight groups based on their ulceration (previous or current) and previous amputation (none, minor or major) status. State nine is an absorbing state (death). If all transitions are fully observable, this model can be decomposed into eight submodels, which can be analyzed using the methods of survival analysis for competing risks. The dependencies of the risk factors (covariates) were included in the submodels using Cox-like regression. The transition intensities and relative risks for covariates were calculated from long-term data of patients with diabetic foot ulcers collected in a single specialized center in North-Rhine Westphalia (Germany). The detected estimates were in line with previously published, but scarce, data. Together with the interesting new results obtained, this indicates that the proposed model may be useful for studying disease progression in larger samples of patients with diabetic foot ulcers. PMID- 26814724 TI - 13th European Congress of Trauma and Emergency Surgery : May 12 - 15, 2012 Basel, Switzerland. PMID- 26814725 TI - Focus on Proximal Humeral Fractures. PMID- 26814726 TI - Biology and Biomechanics in Osteosynthesis of Proximal Humerus Fractures. AB - Surgical treatment of proximal humeral fractures still remains a challenge. This is primarily due to the fact that sufficient implant fixation in humeral head fractures is often not achieved due to substantial bone tissue loss with increasing age. In the last few years the locking plates and locking nails have been introduced into clinical practice with varying results. The biomechanical studies have focused on locking plate osteosynthesis as well. The following paper focuses on bone quality, biomechanical studies and biology of proper osteosynthesis and reviews the most recent literature. PMID- 26814727 TI - Plating in Proximal Humeral Fractures. AB - Improved imaging, updated knowledge regarding humeral head perfusion and adapted fixation techniques with implants having better purchase also in osteopenic bone, have influenced the treatment of proximal humeral fractures in recent years. Demographic evolution and a more active population even among the older age groups will increase the incidence of this fracture, which is already the third most frequent fracture after hip and distal radius fractures in elderly patients. Long-term morbidity related to the treatment of these fractures like avascular humeral head necrosis, non-union, malunion, shoulder stiffness, persistent pain and functional disability are the challenging factors to be overcome. Plate osteosynthesis with angular stable implants have shown to address some of these problems and to broaden the spectrum of indication towards anatomic fracture stabilization even for severely displaced three- and four-part fractures instead of replacing the humeral head with an endoprosthesis, as long as a stable fixation is possible. Open access surgery is often needed for anatomic reconstruction of complex and displaced fractures. This calls for immediate postoperative mobilization with active-assisted ROM exercise to prevent subdeltoidal adhesions. Even though plating of proximal humeral fractures with angular stable implants has shown promising first clinical results, there still remain elevated complication rates especially in the elderly osteoporotic patient population. Recent clinical reports using angular stable plates provided only data with a low level of evidence to help in decision-making. The comparison with historical series using non-angular stable plates in respect to the long-term morbidity should help to better evaluate the value of locked plates inserted with less-extensive soft-tissue exposure. PMID- 26814728 TI - Proximal Humeral Fractures: Nailing. AB - Treating proximal humeral fractures surgically has always been a challenge for the orthopaedic trauma surgeon. The challenge was and is due to numerous factors such as the specific anatomy of the proximal humerus, problems of an adequate approach and exposure of the fracture and different fracture fragments, possible iatrogenic injuries to the rotator cuff on approach and the detrimental effects of the former on the latter's gliding and contracting ability after surgery. Furthermore, the very different fracture patterns that can occur at the proximal humerus, the shear number of fragments which can be of extremely bad bone quality, the necessity for anatomic reduction of these fragments with an implant that will allow for a stable osteosynthesis and at the meantime will not impinge in the subacromial area and lastly, the intention of the physician-in-charge to commence with physical therapy as soon as possible post OP. All of these added to the fact that not one fixation technique with one certain implant could be recommended as a treatment or implant of choice in dealing with these difficult fractures. Most of the supposedly applicable surgical techniques and implants had major setbacks such as being limited to only very expert hands, necessitating a long-standing postoperative immobilisation, resulting in secondary loosening of implants, secondary loosening of reduction or impaired bone healing and, despite all efforts, finally led to poor function at the shoulder. With the advent of angular stable implants such as angular stable, anatomically contoured plates designed for proximal humeral fractures only and special angular stable nails for the same or similar indications the treatment options and the quality of treatment in this area was much improved. Our experience with angular stable nails of two different manufacturers in now more than 320 implantations reveals that indications for the surgical treatment of such fractures can be extended constantly, that the number of complications will simultaneously decline, the necessity for primary joint arthroplasty even in multiple fragment fractures is minimal and that long-term results are, comparing the published results in the literature with those of our institution, equal if not superior to other treatment options. PMID- 26814729 TI - Fixation of Proximal Humeral Fractures with an Intramedullary Nail: Tipps and Tricks. AB - Antegrade interlocking nailing has been established as a valid option of treatment in proximal humeral fractures which follows the principles of minimum invasive surgery. The introduction of angular stability into intramedullary nailing has increased the stability of reconstruction even in osteoporotic fractures. The outcome of the surgical procedure essentially depends on the adequate intraoperative management of the specific features and challenges of the corresponding fracture type. The creation of the correct nail entry point is crucial for anatomic reduction and stability of the reconstruction, as well. The knowledge on intraoperative reduction aids and additional tools of enhancing the stability of the reconstruction alleviates a mechanically sound application of antegrade intramedullary nailing in most highly unstable proximal humeral fractures. PMID- 26814730 TI - Primary Joint Replacement in Proximal Humeral Fractures. AB - The surgical treatment of proximal humeral fractures constitutes a great challenge. Not all fracture types can be successfully reconstructed. Indications for a primary joint replacement arise from critical fracture patterns and defined ischemia-predicting criteria in the elderly. Good functional results are received by a soft-tissue preserving surgical technique, a secure tuberosity attachment and accurate soft tissue balancing of the rotator cuff, a correct restoration of height, retrotorsion and offset, and an appropriate aftertreatment. Multicenter studies observed an averaged Constant Murlay Score of 56 to 73.5 points. 79% of the patients had no or only mild pain in the follow up, ROM was acceptable (41.9% Anteversion >90 degrees , 34.7% Abduction >90 degrees ). Generally, subjective evaluations are much better than objective results. The incidence of complications after primary humeral head replacement is still relatively high, whereas the 10-year-survival-rate of shoulder hemiarthroplasties was found to be 100%, currently. PMID- 26814731 TI - Arthroscopical Findings after Antegrade Nailing of a Proximal Humeral Fracture : Case Report and Review of the Literature. AB - Proximal humeral fractures represent up to five percent of all fractures in adults, commonly found in elderly patients. The final functional results after different operative procedures are among other factors dependent on whether or not a rotator cuff lesion is pre-existent, prior to the fracture, and how its surgical therapy is carried out. However, to what extent prior rotator cuff tears in this special patient group contribute to the functional outcome remains widely unclear. In our institution antegrade intramedullary nailing is the treatment of choice for proximal humeral fractures. One critical point of this technique is the unavoidable split of the rotator cuff on the approach to the proximal humerus and the insertion of the nail through the incised cuff. We report on a case of an impingement after antegrade intramedullary nailing of a proximal humeral fracture. Diagnostic glenohumeral arthroscopy revealed neither a residual lesion of the former rotator cuff incision nor a chondral lesion at the former insertion site of the nail. In the same session subacromial decompression and a nettoyage of adhesions were performed. We assume that splitting the rotator cuff for the insertion of an antegrade nail in a proximal humeral fracture is less relevant than previously assumed and described. PMID- 26814732 TI - Stent Grafts for Acute Traumatic Injury of the Thoracic Aorta: A Single-Centre Experience. AB - OBJECTIVES: The presented study reveals the single centre experiences with the minimally invasive endovascular repair for acute traumatic thoracic aortic lesions in the care of multitrauma patients. METHODS: We reviewed ten patients with acute traumatic thoracic aortic lesions treated with a thoracic aortic stent graft between April 2001 and December 2006. The prospective collected data included age, sex, injury severity score, type of endovascular graft, endovascular operation time, length of stay, length of stay in the intensive care unit, and mortality. Followup data consisted of contrast-enhanced spiral computed tomography at regular intervals. RESULTS: All patients (m:f 5:5; median age, 46 years; interquartile range [IQR], 29-68.5 years) suffered severe traumatic injury, the median Injury Severity Score was 39.5 (IQR 37.3-43). All endovascular procedures were technically successful, and the median operating time for the endovascular procedure was 90 min (IQR, 65-120 min). The overall hospital mortality was 20% (n = 2), and all deaths were unrelated to the aortic rupture or stent placement. No incidence of paraplegia was present. No intervention-related mortality occurred during a median follow-up of 14.7 months (IQR, 9.7-55.8 months). CONCLUSION: The endovascular approach to acute traumatic thoracic aortic lesions is feasible, safe, and effective in multitrauma patients. The low endovascular therapy-related morbidity and mortality in the postoperative period is encouraging. The results seem to be favorable to those published of open emergency repair. PMID- 26814733 TI - Perioperative Application of a Serum Protein Solution (Biseko((r))) After Proximal Femur Fracture of Elder Patients. AB - Fractures of the proximal femur are frequently seen in elderly people and will increase due to the demographic development of most industrialized countries. Early operation of dislocated fractures with either osteosynthesis or hemiprothesis has become a standard treatment for this type of injury. The high co-morbidity often leads to secondary complications like infections still resulting in a perioperative mortality rate of 11%. The perioperative infusion regime might influence the postoperative inflammatory response. Therefore Biseko((r)), a serum protein solution, was compared to albumin and crystalloid infusion (Elomel). A total of 45 patients with proximal femur fractures were randomly assigned to either of the groups and received 500 ml of the infusion on 3 days starting from the day of operation. The Biseko((r)) group showed significantly lower CRP levels, less infections and antibiotic treatment as well as a better clinical outcome referring to the TISS28 and APACHE Score. Concerning IL-6, IL-8, IL-10 and serum leukocytes no significant differences were observed. The result shows a beneficial influence of the serum protein solution Biseko((r)) concerning the number of perioperative complications. The design of this study and the small number of patients does not yet allow any conclusion concerning the effectiveness of this treatment. PMID- 26814734 TI - A Retrospective Study of Five Clinical Criteria and One Age Criterion for Selective Prehospital Spinal Immobilization. AB - Full spinal immobilization of blunt trauma victims is a widely accepted prehospital measure, applied in order to prevent (further) damage to the spinal cord. However, looking at the marginal evidence that exists for the effectiveness of spinal immobilization, and the growing evidence for the negative effects following immobilization, a more selective protocol might be able to reduce possible morbidity and mortality as good as the present prehospital immobilization protocol. In a retrospective study, the sensitivity of a selective prehospital immobilization protocol that adds an age criterion to five clinical spine clearance criteria is examined. MATERIALS AND METHODS: Based on ICD-9 codes, all patients admitted to the trauma center diagnosed with spinal fractures with or without spinal damage were identified. The sensitivity of the combination of five clinical criteria (reduced awareness, evidence of intoxication, neurological deficit, pain of the spine on palpation, (significant) distracting injury) and an age criterion (65 years or older at time of accident) was determined. If one or more criteria were positive, standard full immobilization would be indicated. The other patients would not have been immobilized. RESULTS: A total of 238 blunt trauma victims primarily admitted to the trauma center were included for this study. Median age of the included patients was 39 years (range 5-98), with 32.8% female. A total of 236 had at least one positive criterion (sensitivity 99.2%). The two missed patients were male, 40 and 41 years old. Radiology showed a small fissure in the arch of C2, and a transverse process fracture of L3, respectively. Both patients were discharged the next day without complications or medical interventions. CONCLUSION: In this retrospective study, a selective protocol based on clinical criteria instead of trauma mechanism showed 99.2% sensitivity for spinal fractures with or without spinal cord damage. Based on this study and the current controversy surrounding spinal immobilization, a prospective study should be considered to evaluate the five clinical criteria and one age criterion in the prehospital setting. PMID- 26814735 TI - Early Placement of Optional Vena Cava Filter in High-Risk Patients with Traumatic Brain Injury. AB - OBJECTIVES: Patients sustaining severe trauma are at high risk for the development of venous thromboembolic events (VTE). Pharmacologic VTE prophylaxis may be contraindicated early after trauma due to potential bleeding complications. The purpose of this study was to evaluate safety and feasibility of early prophylactic vena cava filter (VCF) placement and subsequent retrieval in multiple injured patients with traumatic brain injury (TBI). METHODS: Analysis of single-institution case series of consecutive patients who received a prophylactic VCF after severe TBI (Abbreviated Injury Scale, AiS >= 3) between August 2003 and October 2006. RESULTS: A total of 34 optional VCF were prophylactically placed with a median delay of 1 day after trauma (range, 0-7 days). All patients had sustained multiple injuries (median Injury Severity Score 41, range, 18-59) with severe TBI (median AiS 4, range 3-5). Median age was 41 years (range, 17-67 years). Two patients had succumbed before potential filter retrieval. Of the remaining patients, 27 (84%) had their filters uneventfully retrieved between 11 and 32 days (median, 18 days) after placement with no retrieval-related morbidity. Five VCF (16%) were left permanently. In one patient (3%) early inferior vena cava occlusion and deep venous thrombosis occurred 14 days after VCF placement. Symptomatic pulmonary embolism was observed in one patient (3%) 5 days after VCF retrieval. Overall trauma-related mortality was 9%. CONCLUSIONS: Early VCF placement may be of benefit for multiple injured patients with TBI when pharmacologic VTE prophylaxis is contraindicated. VCF retrieval is safe and feasible. Filter placement- and retrieval-related morbidity is low. PMID- 26814736 TI - The Evaluation of Protective Effects of FK-506 on Neural Ischemic-Reperfusion Injury: an Experimental Study. AB - OBJECTIVE: In this study, we aimed to delineate the mode of neuroprotective action of FK-506, and demonstrated that FK-506 could decrease oxidative stress and apoptotic cell death in an in vivo rat model of neural ischemia-reperfusion after hemorrhagic shock. METHODS: Thirty rats were used as experimental subjects and divided into five equal groups. Group A rats (sham group, n = 6) were anesthetized and craniotomies were performed for collecting brain tissue samples. In group B ischemia-reperfusion (I/R + 1 h, n = 6), group C (I/R + 24 h, n = 6), group D (I/ R + 1 h FK-506, n = 6) and group E (I/R + 24 h FK-506, n = 6), systolic blood pressure of the rats decreased to 40-50% of the normal level via bleeding from the femoral vein. Thus, a hemorrhagic shock and ischemic neural tissue model was formed. The bloodwas retained and given to the remaining animals in groups B, C,Dand E via femoral vein for reperfusion 20 min after the procedure. In group D and E, 1 mg/kg FK-506 in 0.5 ml isotonic solution was administered to the rats 5 min before reperfusion. Group B and D rats were sacrificed after 1 h and group Cand E rats were sacrificed 24 h after reperfusion; the rats were sacrificed via bleeding associated with intracardiac puncture. Craniotomy was also performed in groups B, C, D and E and brain tissue samples were fixed using neutral buffered 10% formaldehyde solution for immunohistopathological examination as in group A. Brain tissue superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels, tissue myeloperoxydase (MPO) activities and apoptotic cell analyses with Apo 2.7 immunohistochemically were also performed in all groups. RESULTS: The result of the study revealed that the SOD activities were lower for groups B (I/R + 1 h) and C (I/ R + 24 h) than for group A (sham group) (p < 0.05). In addition, SOD activities were higher in groups D (I/ R + 1 h FK-506) and E (I/R + 24 h FK-506) than in groups B (I/R + 1 h) and C (I/R + 24 h) (p < 0.05). MDA levels, MPO activities and the number of apoptotic cells were lower in group A (sham group) than in groups B (I/R + 1 h) and C (I/R + 24 h) (p < 0.05). In addition to these MDA levels, MPO activities and the number of apoptotic cells were higher in groups B (I/R + 1 h) and C (I/R + 24 h) as compared to groups D (I/R + 1 h FK-506) and E (I/R + 24 h FK-506) (p < 0.05). CONCLUSION: The results suggest that the prophylactic use of FK-506 in an in situ ischemic neural tissue may prevent reperfusion injury. PMID- 26814737 TI - Postoperative Management after Pneumonectomy for Blunt Thoracic Trauma. AB - Pneumonectomy for blunt thoracic injury carries a high mortality rate. We present a case of severe bilateral blunt thoracic injury in which left pneumonectomy was done. The immediate postoperative measures were directed to maintain right heart performance by minimizing hypoxia, avoiding fluid overload and limiting pulmonary hypertension. We believe that this approach contributed to the favorable outcome of this patient. PMID- 26814738 TI - Traumatic Facial Diplegia and Horner Syndrome: Case Report. AB - Traumatic facial diplegia is an uncommon pathology, and is usually associated with bitemporal bone fractures. Traumatic Horner syndrome is mostly associated with carotid artery dissection. We present a case with traumatic facial diplegia and a unilateral Horner syndrome where the mechanisms of injury were unusual. The patient had developed his neurological deficits 9 days following trauma. We discuss the mechanisms of the facial palsy and Horner syndrome and the importance of their diagnosis. PMID- 26814739 TI - Acute Anterior Thigh Compartment Syndrome Revisited: A Case Report and Review of Literature. AB - We present a rare case of acute anterior compartment syndrome of the thigh in a rugby player with no history of trauma during the game. Decompressive fasciotomy with subsequent closure of the wound resulted in good outcome. Acute compartment syndrome of the thigh should be suspected following vigorous exercise and fasciotomy is to be performed on urgent basis. PMID- 26814740 TI - Replacement of the Meniscus with a Collagen Implant (CMI). AB - OBJECTIVE: Replacement of an almost completely absent medial meniscus with a collagen implant (CMI), reconstruction of form and function of the medial meniscus, delay of the development of arthrosis deformans. INDICATIONS: Subtotal degenerative or traumatic loss of the medial meniscus, stable meniscal periphery, stable anterior and posterior meniscal insertions, joint with stable ligaments. CONTRAINDICATIONS: Complete loss of the medial meniscus. Untreated knee ligament instability. Extreme varus deformity. Extensive cartilaginous damage, i.e., levels IV and VI as described by Bauer and Jackson. Advanced unicompartmental or generalized arthrosis. Replacement of the lateral meniscus. SURGICAL TECHNIQUE: Standard anterior arthroscopy portals. Resection of the medial meniscus leaving a complete and stable outer rim. Revitalization of the periphery to promote healing. Measurement of defect size. Insertion and fixation of the CMI with nonresorbable suture material in inside-out technique. POSTOPERATIVE MANAGEMENT: Postoperative knee brace with limited motion in extension/flexion of 0/0/60 degrees until week 4, 0/0/90 degrees until week 6. Coutinuous passive motion within the limits of motion from the 1st postoperative day, actively assisted physiotherapy. No weight bearing for 6 weeks, then increased weight bearing for 2 weeks until full weight bearing is achieved. Cycling can commence from 3 months postoperatively. Full sporting activity after 6 months. RESULTS: 60 patients (19 68 years, average 41.6 years) with subtotal loss of the medial meniscus and varus morphotype were treated from January 2001 to May 2004 as part of a prospective, randomized, arthroscopically controlled study. The sample consisted of 30 patients with high tibial valgus osteotomy combined with implantation of a CMI, and 30 patients with valgization correction osteotomy only. The CMI had to be removed from one patient because of a dislocation. Evaluation on the Lysholm Score, IKDC (International Knee Documentation Committee), and subjective pain data revealed only slight, nonsignificant differences for 39 patients after 24 months (CMI and correction n = 23; correction only n = 16). The chondroprotective effect of the CMI in the long term remains to be seen. PMID- 26814741 TI - Abstracts : 10th Congress of the EMN - Euroacademia Multidisciplinaria Neurotraumatologica, May 19-21, 2005 Rotterdam, The Netherlands. PMID- 26814742 TI - Abstracts : 11th Congress of the EMN - Euroacademia Multidisciplinaria Neurotraumatologica, March 16-18, 2006 Warsaw, Poland. PMID- 26814743 TI - Introduction to the third "Focus-on" issue specially devoted to papers within the field of the ESTES section for Disaster and Military Surgery. PMID- 26814744 TI - Injury types of victims in the 12th May 2008 Wenchuan earthquake: analysis of 1,038 patients in Jiangyou City. AB - BACKGROUND: On 12th May 2008, a devastating earthquake of magnitude 8.0 struck Wenchuan, Sichuan Province of China, resulting in tremendous loss of lives and property. METHODS: We conducted an analysis of the types and distribution of the injuries among the wounded treated by a medical rescue team within 1 month following the Wenchuan earthquake in Jiangyou City. RESULTS: Within 1 month following the earthquake, 3,038 patients sustaining various traumatic injuries were treated in the emergency medical facility established based in a local hospital. Of these patients, 1,065 were hospitalized, including more female than male patients, with an average age of 40.2 years. Most of the patients sustained injuries in Pingwu County, which experienced a seismic intensity of level XI. The majority (91.4%) of the hospitalized patients were admitted in the initial 4 days after the earthquake. The injuries were classified into soft tissue injuries (48.0%), fractures (40.0%), complex injuries (3.1%), and other injuries. The injuries involved most frequently the head and face (28.5%), followed by the upper and lower limbs, chest and back, waist and abdomen, pelvis, and spine. Multiple injuries (15.4%) were also common among these patients. CONCLUSION: The devastating earthquake resulted in a large number of patients with soft tissue injuries frequently in the head and fractures involving mainly the limbs, especially the upper limbs. The injuries sustained in earthquakes are usually serious and complex, often with such complications as shock, infection, and crush syndrome. Multiple injuries are common in the event of an earthquake. PMID- 26814745 TI - Anesthetic management of injuries following the 2008 Wenchuan, China earthquake. AB - PURPOSE: The authors report anesthetic considerations and management of injuries after the 2008 Wenchuan earthquake, Sichuan, China. METHODS: Medical records of surgical patients cared for by the seventh medical team of the Second Military Medical University and the Jiangyou 903 Hospital in the 2008 Wenchuan, China earthquake were reviewed retrospectively with respect to injury patterns, preoperative evaluation, anesthetic techniques, anesthetic management and postoperative recovery. RESULTS: Of 908 patients who were triaged over 2 weeks, 372 (41.0%) patients required admission, of whom 231 (62.1%) patients were managed non-surgically and the remaining 141 (37.9%) patients required emergency surgery under anesthesia. Of the 141 patients, general anesthesia was performed in 16 (11.3%) patients, epidural anesthesia in 55 (39.0%) patients, brachial plexus block in 25 (17.7%) patients, cervical plexus block in seven (5.0%) patients, and monitored anesthesia care in 38 (27.0%) patients. No spinal anesthesia was used in these patients. Minor complications including hypotension, tachycardia and bradycardia were noticed and treated immediately. No severe complications occurred, such as cardiorespiratory arrest, inadvertent intravascular injection, pneumothorax or total spinal anesthesia. CONCLUSION: Epidural anesthesia and peripheral nerve block are the anesthetic techniques of choice for post-earthquake injuries due to limited conditions and appliances. More attention should be paid to preoperative evaluation, anesthetic techniques, anesthetic management, anesthetic application and postoperative recovery according to patient conditions and the limited environment. PMID- 26814746 TI - Taiwan's medical response to the 921 'Chi-Chi' earthquake. AB - OBJECTIVE: The objective of this study was to identify and review literature relevant to the medical response to the 921 earthquake in order to analyse Taiwan's immediate and long-term management of the medical issues arising from the disaster. METHODS: Pubmed and Google Scholar searches were conducted in June 2008 to identify papers relevant to the topic. These were reviewed and the findings of each collated to develop a critical review of Taiwan's response to the earthquake. Pubmed and Google Scholar searches were conducted again in March 2010 to verify the currency of the literature reviewed. RESULTS: A total of 14 papers were identified and reviewed. Many concluded that while disaster response efforts were initiated quickly, the inexperience of the authorities, the timing and location of the earthquake, and the associated destruction of vital infrastructure, meant much of the initial rescue planning and coordination was improvised. This resulted in poor response times by emergency teams, inefficient mobilisation of military and medical resources, poor cooperation between authorities and a failure to fully utilise international assistance when it arrived. CONCLUSION: Taiwan was unprepared for a disaster of the magnitude of the 921 earthquake. The government has since taken initiatives to ensure Taiwan is better prepared for any future large scale disaster, including the establishment of the National Institute for Disaster Management. There is a paucity of literature on the medical response to the disaster. Only one new paper of relevance to the topic has been listed on Pubmed or Google Scholar in recent years. PMID- 26814747 TI - Functional outcome and quality of life in victims of terrorist explosions as compared to conventional trauma. AB - BACKGROUND: Following trauma, the number of preventable deaths is low. Outcome should also be measured in terms of quality of life (QoL). Studies analyzing QoL in trauma patients have been published, but little is known about the long term QoL of victims of terrorist attacks. METHODS: This is a case-control study of casualties of the March 11, 2004 attacks in Madrid. Patients treated for other trauma with similar age and Injury Severity Score (ISS), served as controls. Patients were assessed using the POLO-Chart (VAS, SF-36 and TOP). RESULTS: Fifty eight patients were included, 32 casualties admitted following the March 11, 2004 attacks and 26 controls. Both groups were comparable in age (average = 37), ISS (average = 23) and time from trauma (average = 1,770 days). Subjects demonstrated lower scores for the VAS, and the SF-36 clusters social functioning, role emotional and mental health. There was a tendency towards higher prevalence of symptoms associated to posttraumatic stress disorder (PTSD) in subjects (p = 0.056). Subjects suffered from higher residual pain in the head region (p = 0.032). Strong association was found between the presence of symptoms associated to depression, anxiety and PTSD and worse QoL (p < 0.001). CONCLUSION: Subjects present more emotional distortions, residual pain in the head region and a tendency towards a worsened perception of their own health and wellness. They also present symptoms associated to PTSD more frequently. The presence of symptoms associated to PTSD, depression or anxiety was an independent variable related to lower QoL in both groups. PMID- 26814748 TI - Pattern of civilian gunshot wounds in Durban, South Africa. AB - To evaluate the pattern, demographics, circumstances behind events and patient outcome of civilian gunshot wounds (GSWs), we conducted a prospective review in a surgical department in Durban, South Africa over a period of 9 months. MATERIALS AND METHODS: All patients admitted with GSWs to Prince Mshyeni Memorial Hospital were included in this study from June 2006 to February 2007. Patients' characteristics, events during assault, time of admission, mode of transport to hospital, pattern of injury and patient outcome were noted. RESULTS: A total of 154 patients with GSWs were included in this study (85.1% males; 14.9% females) with average age of 21 years. Mode of transport to hospital was as follows: private (57.1%), ambulance (31.8%) and unknown (11.1%). The common sites of GSW injury were abdomen (26.6%), upper/lower limbs (25.3%) and chest (8.8%). Circumstances during injury were as follows: armed robbery (59.7%), car-hijacking (10.4%), interpersonal violence (9.1%) and 6.5% were shot by police. Injury to arrival time ranged from 20 min to 24 h (average 200 min). The common complications of GSW injury were superficial wound sepsis (27.4%), prolonged morbidity (7.1%) and empyema (3.2%). The mortality rate was 4.5%, all males. CONCLUSION: This study provides evidence that the burden of GSW-related mortality and morbidity poses a substantial threat to the local public health. A national database for reporting all GSWs is recommended for proper assessment of the magnitude of the problem and to facilitate funding for research into injury prevention. PMID- 26814749 TI - Diagnostic and therapeutic aspects in the treatment of gunshot wounds of the viscerocranium. AB - Gunshot wounds of the viscerocranium are a rare occurrence during times of peace in Europe. The removal of projectiles is recommended; in some cases, however, this is controversial. The material properties of projectiles and destruction of anatomical landmarks make it difficult to determine their precise location. Therefore, navigation systems and cone-beam computed tomography (CT) provide the surgeon with continuous intraoperative orientation in real-time. The aim of this study was to report our experiences for image-guided removal of projectiles, the use of cone-beam computed tomography and the resulting intra- and postoperative complications. We investigated 50 patients with gunshot wounds of the facial skeleton retrospectively, 32 had image-guided surgical removal of projectiles in the oral and maxillofacial region, 18 had surgical removal of projectiles without navigation assistance and in 28 cases we used cone-beam CT in the case of dislocated projectiles and fractured bones. There was a significant correlation (p = 0.0136) between the navigated versus not navigated surgery and complication rate (8 vs. 32%, p = 0.0132) including major bleeding, soft tissue infections and nerve damage. Furthermore, we could reduce operating time while using a navigation system and cone-beam CT (p = 0.038). A high tendency between operating time and navigated surgery (p = 0.1103) was found. In conclusion, there is a significant correlation between reduced intra- and postoperative complications including wound infections, nerve damage and major bleeding and the appropriate use of a navigation system. In all these cases we were able to present reduced operating time. Cone-beam CT plays a key role as a useful diagnostic tool in detecting projectiles or metallic foreign bodies intraoperatively. PMID- 26814750 TI - Gunshot injury without direct injury to the cord may lead to complete paraplegia. AB - Paraplegia following gunshot injury without direct injury to the cord is extremely rare. We describe the case of a 31-year-old woman who was admitted to our trauma resuscitation unit for a penetrating gunshot wound to the abdomen with hemorrhagic shock and paraplegia. Computed tomography (CT) scan of the abdomen showed severe hepatic and pulmonary injuries, with the trajectory of the missile away from the spinal canal. Magnetic resonance imaging (MRI) confirmed a spine contusion from T8 to T10. After 24 months, no significant neurologic improvement occurred. Physicians managing severe trauma should be aware of the possibility to observe severe neurologic deficit following gunshot wounds even without violation of the spinal canal. These injuries might be in relation to the kinetic energy emission to the surrounding tissue by the missile. PMID- 26814752 TI - Toward a new definition of 'refugee': is the 1951 convention out of date? AB - Definitions, by necessity, may change or need to be changed to accommodate situations that arise. The United Nations recognized that the emergence of new refugee situations required changes in the Convention. These changes were codified in the 1967 Protocol Relating to the Status of Refugees. The issue of what constitutes a 'refugee' has been changing over time. As new classifications of refugees develop, there needs to be changes in the definition of what is a refugee. There has been a growing consensus in the international arena to recognize those displaced by environmental causes. We need to take steps to develop an inclusive definition of refugee that includes those displaced by environmental causes. PMID- 26814751 TI - Acute ischemia of the lower limb after injury by gunshot: case report and review of literature. AB - INTRODUCTION: Civilian and military vascular trauma has evolved dramatically. It is estimated that 80% of all cases of vascular injuries are due to peripheral vascular trauma, most involving the lower extremities. Arterial below-knee injuries by gunshot still remain a challenge, with an associated rate of amputation of 20-54%. MATERIAL AND METHODS: This case reports a 48 year-old male patient who sustained a gunshot below his left knee. At hospital admission, loss of substance and hemorrhage at the medial and lateral faces of the upper third of his left leg were present with signs of distal ischemia. Arteriography revealed infra-popliteal arterial lesions of the three arterial axes. Two reversed great saphenous vein interposition grafts were performed into the anterior and posterior tibial arteries with immediate revascularization of the left leg and foot. Later, soft tissue reconstruction was accomplished by a split-thickness skin graft. RESULTS: At the fifth month of follow-up, the left leg and foot were viable with good healing, without limitations and with controlled pain. Posterior tibial and dorsalis pedis pulses were palpable. CONCLUSION: This case report shows the importance of an adequate team approach for treatment of a gunshot extremity injury with vascular lesion. The authors want to highlight the scientific background evidence and the value of comparing worldwide civilian trauma center outcomes, mostly reported previously from the military field. PMID- 26814753 TI - Traumatic limb amputations at a level I trauma center. AB - INTRODUCTION: The purpose of this study was to analyze the epidemiology and outcomes after traumatic amputation of the upper (UEA) and lower (LEA) extremities. METHODS: The Los Angeles County + University of Southern California Medical Center trauma registry was utilized to identify all patients sustaining traumatic amputation during the years 1996-2007. The demographics, mechanism of injury, clinical characteristics, associated injuries, surgical procedures, complications, and outcomes were obtained for these patients. RESULTS: During the 12-year study period, 130 patients suffered limb amputation, accounting for 0.25% of all trauma admissions. Thirteen patients (10%) were excluded because they were transferred from another facility after amputation or died in the emergency department. Of the remaining 117 patients, mean age was 38.1 +/- 16.4 years and 77.8% were male. The predominant mechanism of injury was automobile versus pedestrian (27.4%), followed by work-related accidents (23.9%). Patients struck by vehicles were more likely to suffer LEA (93.8% versus 6.2%, p < 0.001), while patients with work-related accidents were more likely to sustain UEA (81.5% versus 18.5%, p < 0.001). Only nine patients underwent reattachment, all of which were for UEA and unsuccessful. Overall, 24.8% developed a complication during their hospital course, 55.2% of which were extremity related. Overall mortality was 3.4%, primarily attributed to associated severe traumatic brain injuries and thoracic injuries. Patients with LEA had longer hospital and intensive care unit (ICU) length of stay; however, after adjusting for confounders, this difference did not reach statistical significance (adjusted mean difference: 2.1 and 1.2 days, p = 0.69 and 0.79, respectively). A higher percentage of patients with LEA required discharge to a skilled nursing facility or rehabilitation center when compared with patients with UEA (29.6% versus 4.8%, p = 0.001). CONCLUSIONS: Traumatic limb amputation is a rare consequence of civilian trauma. Amputation is rarely the primary cause of death; however, these devastating injuries are associated with significant intensive care unit and hospital lengths of stay. Although no mortality difference was detected, when compared with patients with upper extremity amputations, patients with lower extremity amputations were more severely injured, required revision extremity surgery more often, had a higher complication rate, and more frequently required discharge to a long-term facility. PMID- 26814754 TI - Prehospital triage, discrepancy in priority-setting between emergency medical dispatch centre and ambulance crews. AB - BACKGROUND: The timely provision of emergency medical services might be influenced by discrepancies in triage-setting between emergency medical dispatch centre and ambulance crews (ACR) on the scene resulting in overloaded emergency departments (ED) and ambulance activities. The aim of this study was to identify such discrepancies by reviewing ambulance transports within a metropolitan city in the western region of Sweden. METHODS: All data regarding ambulance transports in Gothenburg, Sweden, during a 6-month period were obtained and analyzed by reviewing the available registry. RESULTS: There was a discrepancy between emergency medical dispatch centre and ACR in priority setting, which may result in a number of unnecessary transports to the hospital with consequent overloading of ED and a negative impact on ambulance availability. CONCLUSION: Appropriate ambulance use is one important part of emergency preparedness. Overuse results in decreased emergency medical services (EMS) availability and ED-overcrowding. Several factors, such as an imprecise triage system and increased public demands, may influence such overutilization. Improving the triage system and comprehensive public education on appropriate use of ambulances are two important steps toward a better use of national EMS resources. PMID- 26814755 TI - Flexor tendon repair using a new suture technique: a comparative in vitro biomechanical study. AB - INTRODUCTION: The purpose of this experimental study was to evaluate the biomechanical characteristics of two new four-strand core suture techniques for flexor tendon repair. MATERIALS AND METHODS: The two new suture techniques (Marburg 1, Marburg 2) are characterized by four longitudinal stitches which are anchored by a circular or semicircular suture. They were compared with three commonly used core suture techniques (modified Kessler, Tsuge, Bunnell). Fifty porcine flexor tendons were randomly assigned to one of the five core suture techniques. Outcome measures included ultimate tensile strength, maximum of lengthening, mode of failure and 1 mm gap formation force. RESULTS: The highest ultimate tensile strength was found for the modified Kessler technique (115 N). Both new techniques showed an ultimate load exceeding 50 N (57 N for Marburg 1, 54 N for Marburg 2). The Marburg 1 technique showed the highest gap resistance of all tested suture techniques. The Bunnell and Tsuge core suture techniques produced the poorest mechanical performance. CONCLUSION: From these experimental results, the new Marburg 1 core suture technique can be considered for flexor tendon repair in a clinical setting with the use of active motion protocols. PMID- 26814756 TI - Radial head arthroplasty with an uncemented modular metallic radial head prosthesis: short- and mid-term results. AB - BACKGROUND: In comminuted radial head fractures, arthroplasty is an alternative treatment to open reduction and internal fixation or radial head excision. The purpose of this study was to evaluate the short- and mid-term results after the implantation of the EVOLVETM uncemented modular metallic radial head prosthesis. METHODS: Twenty-five patients with an unreconstructible comminuted radial head fracture were treated with the EVOLVETM prosthesis. Two groups were formed in order to evaluate short-term (mean 1.6 years, range 1-2.3 years) and mid-term (mean 5.1 years, range 3-7.2 years) results. The short-term group consisted of 10 patients and the mid-term group of 15 patients. Objective physical outcome (ROM, grip strength) and outcome scores (Broberg/Morrey score, DASH) as well as radiological findings (periprosthetic lucency, prosthetic sizing, heterotopic ossification, posttraumatic osteoarthritis) were evaluated. RESULTS: Significant impairments in ROM and grip strength were observed in the affected arm. Differences in impairment of the affected arm between the two groups were not significant. There were no significant differences in the outcome scores between the two groups, with good results obtained overall. Understuffing was observed in 3 patients. Three patients had severe and 5 had no periprosthetic lucency. The groups barely differed in periprosthetic lucency. CONCLUSIONS: Radial head arthroplasty with the EVOLVETM prosthesis gave good results in terms of objective physical outcome and outcome scores at short- and mid-term follow-up. Periprosthetic lucency does not affect the outcome negatively. We assume that periprosthetic lucency does not necessarily imply prosthesis loosening in which revision is required. Radiological findings and the severity of the initial injury do not necessarily correlate with results. PMID- 26814758 TI - Focus on Blunt Solid Organ Injuries. PMID- 26814757 TI - An Update on the Use of Animal Models in Diabetic Nephropathy Research. AB - In the current review, we discuss limitations and recent advances in animal models of diabetic nephropathy (DN). As in human disease, genetic factors may determine disease severity with the murine FVB and DBA/2J strains being more susceptible to DN than C57BL/6J mice. On the black and tan, brachyuric (BTBR) background, leptin deficient (ob/ob) mice develop many of the pathological features of human DN. Hypertension synergises with hyperglycemia to promote nephropathy in rodents. Moderately hypertensive endothelial nitric oxide synthase (eNOS(-/-)) deficient diabetic mice develop hyaline arteriosclerosis and nodular glomerulosclerosis and induction of renin-dependent hypertension in diabetic Cyp1a1mRen2 rats mimics moderately severe human DN. In addition, diabetic eNOS(-/ ) mice and Cyp1a1mRen2 rats recapitulate many of the molecular pathways activated in the human diabetic kidney. However, no model exhibits all the features of human DN; therefore, researchers should consider biochemical, pathological, and transcriptomic data in selecting the most appropriate model to study their molecules and pathways of interest. PMID- 26814759 TI - Current Trends in the Management of Blunt Solid Organ Injuries. AB - The management of patients with solid organ injuries has changed since the introduction of technically advanced imaging tools, such as ultrasonography and multiple scan computerized tomography, interventional radiological techniques and modern intensive care units. In spite of this development in the management of these patients, major solid organ traumas can still be challenging. There has been great improvement in the non-operative management (NOM) of intra-abdominal solid organ injury in recent decades. In most cases treatment of injuries has shifted from early surgical treatment to NOM. PMID- 26814760 TI - Is the Grading of Liver Injuries a Useful Clinical Tool in the Initial Management of Blunt Trauma Patients? AB - BACKGROUND: Computed tomography (CT) has become the preferred method for evaluation of the abdomen for victims of blunt trauma. Grading of liver injuries, primarily by CT, has been advocated as a measure of severity and, by implication, the likelihood for intervention or complications. We have sought to determine if grading of liver injuries, as a clinical tool, affects immediate or extended management of patients. METHODS: We have retrospectively reviewed all patients sustaining blunt liver injuries as diagnosed by CT over a five-year period at a Level I trauma center to determine if grading of injury influenced management. The AAST organ scaling system was utilized (major grade 4-5, minor grade 1-3), as well as the ISS, AIS, mortality, morbidity, and treatment. There were 133 patients available for review. The patients were grouped into major (n = 20) and minor (n = 113) liver injuries and operative (n = 12) and nonoperative (n = 121) management. RESULTS: Major liver injuries had a higher ISS (39 + 13 vs. 27 + 15, p = 0.001) and were more likely to require operative intervention (5/20 vs. 7/113, p = 0.02). Mortality in this group was not different (major vs. minor), and there were no differences in the incidence of complications. Twelve patients (9%) required operation, all for hemodynamic instability, all within 24 h, and 11/12 within 6 h. At operation 8/12 patients had other sources of bleeding beside the liver injury, and 7/12 had minor hepatic injuries. The operative patients had higher ISS and AIS scores (head/neck, chest, abdomen, extremities) than those managed nonoperatively. More patients died in the operative group (6/12 vs. 8/121, p = 0.0003). There were more pulmonary (6/12 vs. 16/121, p = 0.005), cardiovascular (6/12 vs. 19/121, p = 0.01), and infectious (5/12 vs. 20/121, p = 0.049) complications in the operative group. There were 14 deaths overall; 13/14 were due to traumatic brain injury, and 8/14 required urgent operation for hemorrhage. CONCLUSIONS: In conclusion, grading of liver injuries does not seem to influence immediate management. Physiologic behavior dictated management and need for operative intervention, as well as prognosis. However, both major hepatic injuries and need for early operation reflected overall severity and the possibility of associated injuries. PMID- 26814761 TI - Nonoperative Management of Blunt Splenic Trauma: Also Feasible and Safe in Centers with Low Trauma Incidence and in the Presence of Established Risk Factors. AB - BACKGROUND: Treatment of blunt splenic trauma has undergone dramatic changes over the last few decades. Nonoperative management (NOM) is now the preferred treatment of choice, when possible. The outcome of NOM has been evaluated. This study evaluates the results following the management of blunt splenic injury in adults in a Swedish university hospital with a low blunt abdominal trauma incidence. METHOD: Fifty patients with blunt splenic trauma were treated at the Department of Surgery, Lund University Hospital from January 1994 to December 2003. One patient was excluded due to a diagnostic delay of > 24 h. Charts were reviewed retrospectively to examine demographics, injury severity score (ISS), splenic injury grade, diagnostics, treatment and outcome measures. RESULTS: Thirty-nine patients (80%) were initially treated nonoperatively (NOM), and ten (20%) patients underwent immediate surgery (operative management, OM). Only one (3%) patient failed NOM and required surgery nine days after admission (failure of NOM, FNOM). The patients in the OM group had higher ISS (p < 0.001), higher grade of splenic injury (p < 0.001), and were hemodynamically unstable to a greater extent (p < 0.001). This was accompanied by increased transfusion requirements (p < 0.001), longer stay in the ICU unit (p < 0.001) and higher costs (p = 0.001). Twenty-seven patients were successfully treated without surgery. No serious complication was found on routine radiological follow-up. CONCLUSION: Most patients in this study were managed conservatively with a low failure rate of NOM. NOM of blunt splenic trauma could thus be performed in a seemingly safe and effective manner, even in the presence of established risk factors. Routine follow-up with CT scan did not appear to add clinically relevant information affecting patient management. PMID- 26814763 TI - Conservative Management of Major Blunt Renal Trauma with Extravasation: A Viable Option? AB - OBJECTIVES: To evaluate our experience in the management of patients with major blunt renal trauma treated at a major urban trauma center during the last ten years. PATIENTS AND METHODS: The medical records of 72 patients with major blunt renal lacerations treated from 1998 to 2008 were reviewed retrospectively. Patients were broken down into two groups based on whether they were managed conservatively (group 1) or surgically (group 2). Each group was compared with respect to the initial evaluation, computerized tomography findings, associated injuries, hospital stay, transfusion requirements, nephrectomy rate, complications and follow-up imaging. RESULTS: There were 57 patients with grade IV and 15 patients with grade V renal injuries. Of these, 51 (70.8%) patients were managed conservatively (48 with grade IV and 3 with grade V) and 21 (29.2%) patients were managed surgically (9 with grade IV and 12 with grade V). Patients in group 1 had significantly lower transfusion requirements (3.1 vs. 7.5 units, p < 0.0001), shorter hospital stays (11.8 vs. 15.9 days p < 0.003) and fewer complications (21.6 vs. 76.1%, p < 0.001). No death was observed in group 1, while three in group 2 died of major associated injuries. All surviving patients had significant resolution of the extravasation before hospital discharge. CONCLUSIONS: Our data supports the conservative management of grade IV blunt renal parenchymal injuries in the absence of hemodynamic instability of renal origin. Even select patients with grade V parenchymal injuries can undergo a trial of conservative management. PMID- 26814762 TI - Proximal Splenic Artery Embolization In Blunt Splenic Trauma. AB - BACKGROUND: Proximal embolization of the splenic artery (PSAE) has recently been reported for traumatic splenic injury. The suggested mechanism of action entails a decrease in the splenic blood pressure without ischemia due to collateral blood supply. The main complications of selective embolization are continuous bleeding, splenic infarcts and splenic abscesses. The main complications of observation alone are continuous bleeding and formation of splenic pseudoaneurysms. Our aim was to assess the efficacy of PSAE in the cessation of bleeding without formation of pseudoaneurysms, and the outcome of the spleen after such intervention. METHODS: A prospective observational study of all patients undergoing PSAE for traumatic splenic injury in our institution over a 33-month period. Clinical and Doppler sonographic examinations were performed to assess cessation of bleeding, splenic blood flow, and formation of splenic pseudoaneurysms, infarcts or abscesses. RESULTS: During 33 months, 11 patients with blunt abdominal trauma and tomographic evidence of either high grade or actively bleeding splenic injuries were treated by PSAE. During follow-up, no patient underwent surgery or repeated embolization. Preserved blood flow was found on Doppler sonography in 82% of the patients and no pseudoaneurysms were demonstrated. A perisplenic collection was found in one patient and responded well to percutaneous drainage. CONCLUSIONS: Proximal embolization of the splenic artery for severe splenic injury is highly successful in cessation of bleeding while preserving splenic architecture. There were minimal complications in this series demonstrated by clinical and Doppler examinations. PMID- 26814764 TI - Femoral Neck Fractures in Children: A Follow-Up Study of 19 Cases. AB - We studied 20 fractures of the neck of femur in 19 patients under the age of 16 years that were treated in the period from 1998 to 2004. There were nine boys and ten girls with an average age of 11 years. There was one case of Delbet type I (transepiphyseal separation). Thirteen cases were of Delbet type II (transcervical) fractures, four cases were of type III (cervicotrochanteric), and two patients had old fractures (one Delbet type II and one type III). Fourteen fractures were displaced. In our study group, 11 patients were treated surgically by internal fixation while the remaining were treated conservatively by traction followed by hip spica cast application. Mean follow-up was 24 months (range 1-5 years). Avascular necrosis occurred in nine cases (45%). Other complications included coxa vara in two, nonunion in two, postoperative infection in one, and refracture in one. The amount of displacement of the fracture and the quality of reduction and fixation influenced the occurrence of complications such as avascular necrosis and nonunion. PMID- 26814765 TI - Is the Wave Plate Still a Salvage Procedure for Femoral Non-union? Results of 75 Cases Treated with a Locked Wave Plate. AB - OBJECTIVE: To analyse the results of the treatment of aseptic femoral non-unions using a singular locked implant. DESIGN: Consecutive case series. SETTING: A level-1 trauma center with a high number of specialist referrals. PATIENTS: The study is based on a consecutive series of patients with prospective data evaluation. From 1993 to 2003, 75 patients were treated with a wave plate. All patients had persistent non-union of the femoral shaft without clinical or laboratory signs of infection and previous unsuccessful attempts to treat the non union. INTERVENTION: The method of treatment was standardized and included a lateral approach, cancellous bone hip grafting, osteosynthesis with a wave-shaped plate (PPF) and polyaxial locking screws as well as the application of a gentamicin-PMMA chain. MAIN OUTCOME MEASUREMENTS: Time to achieve union, rate of implant failure and number of remaining nonunions after treatment. A total of 75 patients had full follow-up and were included in the study. RESULTS: The union of the fracture was found in 64 patients after the initial procedure. In eight cases a second procedure was performed to achieve union in the form of a second bone graft because of a delay in callus formation. The mean time to union was 7.3 months with a range from 3 to 19 months. The implant failed in three cases accounting for 4% of the total. CONCLUSION: The locked wave plate offers a further reliable treatment for complex aseptic femoral non-unions. PMID- 26814766 TI - The Effects of Hook Plates on the Subacromial Space. A Clinical and MRI Study. AB - The disruption of the acromioclavicular joint is a relatively common injury of the shoulder girdle, often occurring in young athletes. The therapy of third degree injuries (Tossy III or Rockwood III-VI) is still controversial, and several operative techniques are practiced. In a retrospective study, 28 (= 72%) of the total number of 39 cases with a Tossy III disruption operated in our hospital between January 1998 until December 2002 with a hook plate according to Dreithaler were followed up. The average reexamination interval was 3.0 years (range 1.2-5.6 years) after surgery. Special emphasis was laid upon the question, if the hook had any effects on the subacromial space. The study included clinical, sonographic and MRI examinations of both shoulders in direct side-to side comparison. About 86% of the patients were satisfied with the functional outcome, but only 54% with the cosmetic result. This was mostly due to remaining elevation of the lateral clavicula and heterotopic ossifications around the acromioclavicular joint, which were found in 43% of the patients without any functional deficit. The outcome-scores (DASH, Taft, Constant-Murley) yielded on the whole very good and good results. Instability of the AC-joint under load was found in seven patients, in three of these instability was severe, and two patients had a chronic subluxation with functional impairment.The sonographic investigation revealed no specific lesions of the rotator cuff in any patient. Age related degenerative changes were seen in 46%, however, the accentuation of the operated side was only 14%. In MRI there was no case of a complete rotator cuff tear. Corresponding to the sonographic examination increased numbers of exostoses, heterotopic ossifications, and arthrosis of the AC-joint were observed. PMID- 26814767 TI - The Value of Ultrasound in Acute Ankle Injury: Comparison With MR. AB - OBJECTIVE: To assess the value of the ultrasound (US) in different grades of acute trauma by comparing with MR. METHODS: We analyzed 30 patients, of average age 33, with acute ankle trauma, without fracture on standard radiograms. One week after injury all patients were sent for US. We used linear probe 8-15 MHz. Ten days later, the patients were examined on MR. RESULTS: Anterior talofibular ligament was normal in 20.6% by US and in 20.3% by MR. Ligament lesion were found by ultrasound in 40%, proven in only 20.6% by MR. Ultrasound diagnosed 33,3% ruptured ligament, MR found 50% rupture of anterior talofibular ligament. In 80.3% cases the calcaneofibular ligament appeared to be intact with both methods. Ultrasound found stretch ligament in 10.6% cases and MR proved that in 10% cases. In other 6.6% cases, MR found complete rupture. Intraarticular effusion was found in 80.3% patients by US and in 86.6% by MR. Lesion of tendon of long peroneal muscle was found in 40.6% patients by both methods. Lesion of tendon of short peroneal muscle was found in 33.3% lesions and proved by MR in only 20.3% cases. In other patients findings were normal. US found 10% lesions of the tendon of anterior tibial muscle and MR found 10.3% lesions. US found 10.6% lesions of tendon of long halucis flexor and MR found 20%. Our results were statistically analyzed by cross-tabs, the Stuart-Maxwell test, Npar tests and the McNemar test. CONCLUSION: US proved to be a good and reliable method for diagnosing Grade I and II of ankle sprain, but for proper evaluation of Grade III, MR is recommended. PMID- 26814768 TI - The Elastic Bridge Plating of the Forearm Fracture: A Prospective Study. AB - Rigid plate osteosynthesis with compression is still the treatment of choice for forearm fractures to gain anatomic reposition, provide proper rotation and avoid a bridging callus. Due to necessary operative dissection there is a serious risk for infection and malunion. Based on good clinical results with elastic bridge plating at femur, humerus and tibia, this technique was also started to be used for forearm fractures in our clinic in 1995. In a prospective study, 86 of 124 consecutive patients at the age of 35.2 +/- 14.7 years with 129 diaphyseal fractures of the radius or ulna (AO: 37 type A, 36 type B, 13 type C) were analyzed between January 1998 and December 2003. All fractures were stabilized by bridge plating. Radiographic union and clinical outcome were documented. Of the 129, 122 diaphyseal fractures (94.5%) healed within 10.2 +/- 3.4 weeks without complications (no nerve lesions, nonunion, synostosis callus). One re osteosynthesis, one secondary lag screw, and five cancellous bone grafts were necessary before final healing. About 79.1% of the patients had a perfect clinical outcome; 17.4% had additional severe injuries of the same arm. Bridge plating without interfragmentary compression is a reliable surgical procedure even for forearm fractures with low risk of infection and nonunion. PMID- 26814769 TI - Comparison of Injury Pattern in Victims of Bear (Ursus thibetanus) and Leopard (Panthera pardus) Attacks. A Study from a Tertiary Care Center in Kashmir. AB - INTRODUCTION: Patients injured in bear and leopard attacks present with different patterns of injuries and have different mortality rates. A common protocol may not be suitable for the management of injuries inflicted by these two large wild animals. MATERIALS AND METHODS: A retrospective study was conducted by the Department of Orthopedics, Government Medical College Srinagar (India) to compare the injury patterns among victims of bear and leopard attacks. RESULTS: One hundred and fifty-five cases with 120 (77.4%) bear and 35 (22.5%) leopard attacks were recorded over a period of 43 months. Eighty-six males and 34 females including two children were injured in bear attacks. Eleven males and 24 females including 13 children were attacked by leopards. The leopard attacks were usually fatal (48.5%), whereas the bear attacks were mostly nonfatal in nature (1.6%). The patients had a combination of injuries affecting multiple parts of the body. Injuries of the cervical spine, cervical cord, major vessels of neck, pharynx and eye were striking observations in leopard attacks. Fractures of the upper limb, facial and skull bones were common in the victims of bear attacks. The survivors were treated as per advanced life trauma support, with an average follow-up of 24.5 months (5-42 months). CONCLUSION: Wild animals usually attack in remote areas, where composite trauma centers do not exist, and the urgent referrals of these patients will have a significant impact on the final outcome. The management of these patients requires a team approach involving all of the subspecialties of traumatology. PMID- 26814770 TI - Distal Tibial Fracture Fixation with Locking Compression Plate (LCP) Using the Minimally Invasive Percutaneous Osteosynthesis (MIPO) Technique. AB - BACKGROUND: Treatment of distal tibial fractures has always been a challenge. Distal tibia is more superficial, with less soft tissue coverage and blood supply. Therefore, operative treatment can lead to complications. We aim to see the results of the distal tibial fracture fixation with LCP using MIPO. PATIENTS AND METHODS: Twenty-one consecutive patients were prospectively reviewed. AO types 43A, 43B and 43C were included. Fourteen male and seven female patients with a mean age of 51 years were included. RESULTS: Mean time to union was 5.5 months (range 3-13 months). Seventeen fractures healed with good functional outcome. One patient had delayed union. One patient had nonunion and underwent revision; the fracture ultimately healed with good functional outcome. Two patients developed superficial wound infections but the fractures united completely. DISCUSSION: The MIPO technique for distal tibia has shown good results with many additional advantages over the conventional methods. Early mobilization without risk of secondary displacement helps to prevent stiffness and contracture. PMID- 26814771 TI - Cervical Prevertebral Soft Tissue Swelling in the Traumatized Patient: What is Normality in the Intubated Patient? AB - Interpretation of prevertebral soft tissue swelling is generally thought to be invalid in the presence of an endotracheal tube (ETT). There is however little scientific data to support this.We evaluate the prevertebral soft tissue swelling of 43 traumatized patients that have had an endotracheal tube (ETT) placed in the acute setting. A control group of 92 patients were also evaluated which had been subjected to acute trauma and no ETT. There was a significant increase in soft tissue swelling (p < 0.0001) found in the ETT group at the C2 level compared to the non-tube group. There was no significant difference between the two groups at the C4 and C6 levels.We feel that interpretation of prevertebral swelling in the traumatized patient at the C2 level is invalid in the presence of an ETT, and indeed is significantly increased after intubation despite no injury at this level. However, the interpretation of soft tissue swelling at and below C4 remains a useful tool in the evaluation of an occult cervical injury. PMID- 26814772 TI - Insufficient Evidence for Routine Use of Thromboprophylaxis in Ambulatory Patients with an Isolated Lower Leg Injury Requiring Immobilization: Results of a Meta-Analysis. AB - BACKGROUND: There are no generally accepted guidelines for the prevention of venous thromboembolism (VTE) in ambulatory patients requiring immobilization after an isolated lower leg injury. Our objective was to evaluate the effectiveness and safety of pharmacological interventions for preventing VTE in these patients. STUDY DESIGN: Meta-analysis of randomized controlled trials. MATERIALS AND METHODS: We searched PubMed/Medline, EMBASE and the Cochrane Central Register of Controlled Trials for trials with random allocation of thromboprophylaxis, notably low molecular weight heparin (LMWH) versus no prophylaxis or placebo, in ambulatory patients with below-knee or lower leg (including the knee joint) immobilization. Outcome was analyzed using MIX to calculate the pooled risk ratio/relative risk (RR) for each outcome, along with its 95% confidence interval (CI). RESULTS: The RR of asymptomatic deep vein thrombosis (DVT) was 0.66 (95% CI 0.44; 1.02) for below-knee immobilization and 0.51 (95% CI 0.37; 0.70) for lower leg immobilization. Low molecular weight heparin versus no prophylaxis or placebo was evaluated. The incidence of symptomatic DVT and PE was too low to show any statistically significant difference between thromboprophylaxis and controls in both groups. Although only one adverse bleeding event was considered to bemajor, the RR for any adverse bleeding event was 1.94 (95% CI 1.03; 3.67). CONCLUSION: There is insufficient evidence to warrant routine use of thromboprophylaxis in ambulatory patients with below-knee or lower leg immobilization after an isolated lower leg injury. The incidence of symptomatic VTE is too low to show a relevant clinical benefit from thromboprophylaxis. PMID- 26814774 TI - Pneumocephalus Following Severe Head Trauma. AB - It is important to be alert to the possibility of pneumocephalus in patients with head injury. Pneumocephalus is a potentially lethal complication in patients with craniofacial fractures following severe head trauma. A patient presented with intracranial air after he fell down from a height of 4 m. The patient recovered without any neurological deficits after conservative treatment. A time sequence of cerebral CT scans shows how the pneumocephalus developed and finally resolved without surgical intervention. The etiology, diagnosis, treatment and possible complications of this injury are discussed briefly. PMID- 26814773 TI - Acute Traumatic Brain Injury: A Review of Recent Advances in Imaging and Management. AB - Acute traumatic brain injury (TBI) is a major cause of death and disability in young persons worldwide, producing a substantial economic burden on health services. New technology in computed tomography and magnetic resonance imaging is allowing the acquisition of more accurate and detailed information on cerebral pathology post-TBI. This has greatly improved prognostic ability in TBI and enables earlier identification of pathology, making it potentially amenable to therapeutic intervention. Recent advances in the management of TBI have been hampered by a lack of class I evidence arising from difficulties in applying strict study protocols to a patient subset as heterogeneous as post-TBI patients. The most definite benefits in terms of survival after TBI come from admission to a specialist neurosurgical centre, with goal-targeted therapy and intensive care services. Some traditional therapies for the treatment of acute TBI have been proven to be harmful and should be avoided. A number of management strategies have proved potentially beneficial post-TBI, but there is insufficient evidence to make definitive recommendations at present. Future therapies that are currently under investigation include decompressive craniectomy, progesterone therapy, and possibly therapeutic hypothermia. PMID- 26814775 TI - Traumatic Allogenic Bone Implantation. AB - Traumatic allogenic bone implantation is becoming increasingly common in the setting of road trauma and suicide bombings. We present a unique case where a large bony fragment from one individual became embedded in the arm of another person following a "head-on" collision involving two motorbikes. Several management issues are outlined. PMID- 26814776 TI - Stress Fracture of the Femoral Neck in a Young Female Athlete. AB - Stress fractures have been reported to occur in association with running. They typically involve the lower extremity. Although relatively rare, unrecognized or untreated femoral neck fractures carry a much higher morbidity rate than other stress fractures. Stress fractures of the femoral neck should even be considered in young amateur athletes with hip pain. If X-ray is inconclusive, radionuclide bone imaging and MRI can be useful in diagnosing these fractures. This rare diagnosis, as well as classification and treatment options, will be discussed. PMID- 26814778 TI - New solutions for complex bleeding in trauma. PMID- 26814777 TI - Power and pollutant exposure in the context of American Indian health and survival. AB - BACKGROUND: American Indians and Alaskan Natives (AI/AN) are a highly diverse group in terms of culture and language, but share a history of oppression and attempted extermination that has left many with a legacy of poverty and poor health. Cultural and biological survival are important issues for many AI/AN groups. METHODS: Using US criteria, AI/AN groups are more likely to be poor. The US National Center for Health Statistics reports that US AI/ANs have higher mortality and morbidity rates than the US population. While all groups racially defined by the US National Center for Health Statistics have been experiencing a decline in fertility since 1983, AI/ANs seem to be suffering a substantially greater and earlier decline in fertility. Given the importance of fertility in the survival of AI/AN communities, it is important to identify the source of this decline. RESULTS: A recent study of one AI/AN group living along the St. Lawrence River found that obesity and exposure to a particular group of polychlorinated biphenyls were the factors most highly associated with indicators of impaired fertility. Economic factors are often cited as reasons for fertility declines, however in this situation these other factors may have either primary or contributing roles. CONCLUSIONS: If the associations with obesity and toxicant exposure are confirmed, intervening on these factors might be important steps in stemming continued declines in fertility. PMID- 26814779 TI - Modern resuscitation of hemorrhagic shock: what is on the horizon? AB - PURPOSE: Mortality rates among the severely injured remain high. The successful treatment of hemorrhagic shock relies on expeditious control of bleeding through surgical ligation, packing, or endovascular techniques. An important secondary concern in hemorrhaging patients is how to respond to the lost blood volume. A single method that is able to adequately address all needs of the exsanguinating patient has not yet been agreed upon, despite a large growth of knowledge regarding the causative factors of traumatic shock. METHODS: A review of relevent literature was performed. CONCLUSIONS: Many different trials are currently underway to discriminate ways to improve outcomes in the severely injured and bleeding patient. This paper will review: (1) recent advances in our understanding of the effects hemorrhagic shock has on the coagulation cascade and vascular endothelium, (2) recent research findings that have changed resuscitation, and (3) resuscitation strategies that are not widely used but under active investigation. PMID- 26814781 TI - Endovascular therapy in trauma. AB - The practice of medicine has experienced a revolution in the use of catheter based or endovascular techniques to manage age-related vascular disease over the past 15 years. In many scenarios the less invasive, endovascular method is associated with reduced morbidity and mortality than the traditional open surgical approach. Although somewhat delayed, the use of endovascular approaches in the management of certain trauma scenarios has also increased dramatically. With improvements in catheter-based and imaging technologies and a broader acceptance of the value of the endovascular approach, this trend is likely to continue to the benefit of patients. The use of endovascular techniques in trauma can be considered in three broad categories: (1) large-vessel repair (e.g. covered stent repair), (2) mid- to small-vessel hemostasis (e.g. coils, plugs, and hemostatic agents), and (3) large-vessel balloon occlusion for resuscitation (e.g. resuscitative endovascular balloon occlusion of the aorta). While not exclusive, these categories provide a framework from which to consider establishing a trauma-specific endovascular inventory and performance of these techniques in the setting of severe injury. The aim of this review is to use this framework to provide a current appraisal of endovascular techniques to manage various forms: vascular injury, bleeding, and shock; including injury patterns in which an endovascular approach is established and scenarios in which it is nascent and evolving. PMID- 26814780 TI - The epidemic of pre-injury oral antiplatelet and anticoagulant use. AB - BACKGROUND: As the population ages, an increasing number of trauma patients are taking antiplatelet and anticoagulant medications (ACAP) prior to their injuries. These medications increase their risk of hemorrhagic complications, particularly intracerebral hemorrhage. Clopidogrel and warfarin are common and their mechanisms well understood, but optimal reversal methods continue to evolve. The novel direct thrombin and factor Xa inhibitors are less well described and do not have existing antidotes. METHODS: This article reviews the relevant literature on traumatic outcomes with use of ACAP medications, as well as data on ideal reversal strategies. Suggested algorithms are introduced, and future research directions discussed. RESULTS: Although they are beneficial in preventing clot formation, once bleeding occurs ACAP medications contribute to increased morbidity and mortality, particularly in geriatric patient populations. The efficacy of clopidogrel reversal with platelet transfusions and DDAVP remains unclear. Warfarin use is best treated with the algorithm-driven use of plasma, vitamin K, prothrombin complex concentrates (PCCs) and possibly recombinant factor VIIa depending upon specific patient and injury factors. Optimal treatment for direct thrombin and factor Xa inhibitors has yet to be developed, but PCCs are promising for rivaroxaban and apixaban while dabigatran is best treated with medication cessation and the possible addition of activated PCCs or hemodialysis. CONCLUSION: New developments in reversal of the ACAP medications are promising, particularly PCCs for warfarin and the factor Xa inhibitors. Function assays and clear antidotes are needed for the thrombin and Xa inhibitors. Research on outcomes and appropriate treatments is actively ongoing. PMID- 26814782 TI - Electrical burn injuries of 246 patients treated at the University Clinical Center of Kosovo during the period 2005-2010. AB - BACKGROUND: In the developing world, the incidence of electrical injuries has increased in the past few years. Electrical injuries represent approximately 5 % of all burn admissions to burn units in the United States. OBJECTIVE: The objective of this study is to understand the causes of electrical burns in our population, sex, age, duration of treatment, distribution of electrical burns by season, accompanying other traumatic injuries with electrical burns, entry lesions of high-voltage electrocution, location of injuries, the methods of treatment, duration of treatment, and mortality. MATERIALS AND METHODS: This is a retrospective study that included 246 patients with electrical burns treated in the 2005-2010 period at the Department of Plastic and Reconstructive Surgery in Kosovo. The data were collected and analyzed from the archives and protocols of the University Clinical Center of Kosovo. Data processing was done with the statistical package InStat 3. From the statistical parameters the structural index, arithmetic median, and standard deviation were calculated. Data testing was done with the chi(2) test and the differences were considered significant if p < 0.05. CONCLUSION: The high mortality, 9.1 %, and 7 patients (10.6 %) transferred out of our country for treatment is a reflection of the lack of a burn center in our department. PMID- 26814783 TI - Bullhorn and bullfighting injuries. AB - PURPOSE: Our purpose was to present our hospital experience with bullhorn injuries. METHODS: A retrospective analysis of patients in our Trauma Registry (1993-2012). RESULTS: Fifteen patients were included. All were hemodynamically stable on presentation, with a mean Glasgow Coma Scale (GCS) score and a Revised Trauma Score (RTS) of 15 and 11.9, respectively. The Injury Severity Score (ISS) and New Injury Severity Score were 13.6 +/- 6 and 15.9 +/- 9, respectively. Seven had an ISS > 15. Injuries resulted from an isolated blunt trauma (BT) in four, penetrating trauma (PT) in seven, with extensive soft tissue injuries (STI) in three, and a combined BT + PT mechanism in four patients, with extensive STI in all. Three patients had injuries to vessels in the groin, two with prehospital vein ligation. Five patients had abdominal visceral injuries, and another had a sheathed goring, with a traumatic abdominal wall hernia and retroperitoneal hematoma. Four patients had thoracic injuries, and one of them had a traumatic thoracoplasty with a large open thoracic wound, a flail chest, and extensive STI. Two patients had traumatic brain injury, and six had bone fractures. Two-thirds of patients required a surgical procedure under general anesthesia. Morbidity included three surgical site infections, one leg compartment syndrome, and one persistent lymph drainage. There was no mortality, and the mean length of hospital stay was 16 days. CONCLUSIONS: Bullhorn and bullfighting injuries frequently have a multimechanistic origin which goes beyond a pure penetrating trauma. Associated blunt and STI were common in our series, and the overall prognosis of patients admitted to hospital was good. PMID- 26814784 TI - Trauma risk perception related to alcohol, cannabis, and cocaine intake. AB - OBJECTIVE: A high perception of risk may exert a preventive effect against the initiation of risky activities. The aims of the present study were (1) to analyze the risk perception for traumatic incidents according to drug intake (alcohol, cannabis, cocaine, no consumption) by trauma patients admitted to our hospital, and (2) to explore the influence of drugs on trauma recidivism. METHODS: Between 1 November 2011 and 1 April 2012, 404 patients aged between 16 and 70 years were admitted to our hospital for trauma cases. In 363 (89.9 %) of the patients, data were gathered on age, the trauma mechanism, and the consumption of alcohol and other drugs. Out of these 363 patients, 286 (78.8 %) attended a motivational interview and reported their consumption habits and their perception of the risk of trauma after alcohol and/or illegal drug consumption, as well as the antecedents of previous traumatisms. RESULTS: Alcohol and/or illegal drugs were detected in 37 % of the sample, with alcohol being the most frequently detected, followed by cannabis, cocaine, and other drugs. Among the trauma patients with no consumption, a high perception of trauma risk was associated with alcohol intake by 95.9 %, with cannabis consumption by 68.4 %, and with cocaine consumption by 53.4 %, whereas these percentages were significantly lower for patients testing positive for substances (79.3, 21.1, and 8.3 % respectively). Among the patients experiencing their first trauma, the mean age was almost 15 years younger in those who were positive for these substances than in those who were negative (p < 0.001). Finally, a history of previous trauma was reported by a majority (64 %) of the trauma patients testing positive for alcohol and/or drugs, but by a minority (36 %) of those testing negative (p < 0.001). CONCLUSIONS: The low perception of risk associated with alcohol, cannabis, or cocaine consumption by trauma patients under the influence of these substances on admission may be a predisposing factor for recidivism. Recommendations for both primary and secondary prevention are presented. PMID- 26814785 TI - Urban versus rural trauma recidivism: is there a difference? AB - PURPOSE: Understanding the characteristics of trauma recidivists may allow trauma centers to tailor prevention programs. We hypothesized that there would be an increased incidence of violent injuries and falls in the urban vs. rural recidivists, respectively. METHODS: Trauma admissions from 2000 to 2011 were queried for incidences of recidivism. Age (<65 or >=65 years), gender, Injury Severity Score (ISS, <9 or >=9), mortality, and injury cause (fall, violence, or other) were analyzed with univariate analyses to test for differences between urban and rural patients. Significant variables were then included in a binary logistic model and further stratified based on environment. RESULTS: There were a total of 19,600 trauma admissions from 2000 to 2011, representing 18,711 unique patients, with 1,690 admissions (8.6 %) attributed to 801 recidivists (4.3 %). The overall percentages of recidivist trauma admissions attributed to urban and rural patients were 8.6 and 6.9 %, respectively (p < 0.001). When adjusting for age >=65 years as well as falls and violent injuries, patients from urban environments were at 1.12 times higher odds of being a recidivist than their rural counterparts [odds ratio (OR) 1.12; 95 % confidence interval (CI) 1.01 1.25; p = 0.039]. When stratified into rural and urban groups, falls and violent injuries were significant in both groups of recidivist admissions; however, age >=65 years was only significant in rural recidivist admissions. CONCLUSION: An urban trauma admission had 12 % higher odds of being attributed to a recidivist than its rural counterpart, when controlling for age and mechanism of injury (MOI). Age >=65 years was a significant variable in rural but not urban recidivist admissions. Characterizing the recidivist may allow for targeted prevention and intervention programs to decrease repeat hospital visits. PMID- 26814786 TI - Traumatic deaths at hospital: analysis of preventability and lessons learned. AB - PURPOSE: The aim of the present study was to characterize traumatic deaths of major trauma patients occurring in a university trauma centre and to assess retrospectively the quality of given care by evaluating whether any of the deaths could be identified as potentially preventable. METHODS: All consecutive deaths of trauma patients between January 1, 2004 and December 31, 2008 in the Toolo Hospital Trauma Centre were retrospectively reviewed. The inclusion criterion was death of a trauma patient occurring during stay at hospital. Patients aged >65 years with an isolated proximal femoral fracture, burn patients, patients with isolated limb fracture other than femoral or tibial shaft fracture, and patients with isolated traumatic brain injuries were excluded as well as patients admitted more than 24 h after injury. RESULT: A total of 130 patients fulfilled the inclusion criteria. The autopsy reports were obtained for 103 of the cases (80.4 %). The majority of the patients were male, and the median age was 58 years (range 1-95 years). Blunt trauma was the most common type of injury. The most common injury mechanisms were fall from a higher level (31 %), fall from the level of the patient (21 %), and motor vehicle accident (17 %). Of the injuries not diagnosed before autopsy, the most common were liver lacerations, rib fractures, pulmonary contusions, sternum fractures, and blunt cardiac injuries. In our study population 12.5 % of the cases were considered potentially preventable. The reasons for preventability were inadequate treatment of coagulopathy, overuse of opioid medication, and loss of airway as well as failing to treat impending pneumonia and DVT. Trauma resuscitation was inadequate in 7.8 % of the cases. CONCLUSIONS: The most common error made was not recognising and treating traumatic coagulopathy adequately. PMID- 26814787 TI - Diagnosing isolated nasal fractures in the emergency department: are they missed or overdiagnosed? Ten years experience of 535 forensic cases. AB - AIM: Nasal bone is the most common broken bone of the face. Incorrect assessments of nasal trauma are frequently encountered in forensic evaluations. Here, we aimed to determine the reasons and frequency of erroneous assessments of nasal trauma in emergency department (ED). METHODS: This is a cross-sectional multicentric study analyzing the Forensic Medical Department archive retrospectively. Epidemiologic features, type of fracture (depressed or non depressed), and specialty of the doctor examining the cases in ED were studied. Forensic evaluation was reported by analyzing all radiologic examinations (CT and X-ray), medical records, and after repeated physical examination of nasal trauma by the forensic council, consisting of a forensic expert, a radiologist and an otolaryngologist. Nasal fracture was diagnosed when at least two of three physicians agreed. RESULTS: A total of 535 cases (mean age 31.7 +/- 14.4, 87.1 % males) were analyzed. The most common causes of injuries were assault (81.8 %), followed by traffic accident (15.3 %) and falls from a height (2.1 %). There were misdiagnoses in ten patients (1.9 %) and overdiagnosis in 135 (24.5 %). The possibility of fracture overdiagnosis was 13.5 times higher than missing it. General practitioners and emergency physicians have 19.7 times (95 % CI 5.5-22. 3) and 3.4 times (95 % CI 1.5-7.8) the tendency to report soft tissue nasal injuries as non-depressed fractures, respectively. CONCLUSION: We found that nasal fractures are rarely missed while the overdiagnosis was very common. Examination of patients by a general practitioner or an emergency physician without consultation with a specialist and using only plain radiographs were found to be independent parameters affecting overdiagnosis. PMID- 26814788 TI - Autonomic dysreflexia: a possible trigger for the development of heterotopic ossifications after traumatic spinal cord injury? : A clinical longitudinal study. AB - PURPOSE: The aim of this study was to investigate the influence of the initial American Spinal Injury Association Impairment Scale (AIS) category and the conversion rate in acute traumatic tetraplegic patients on the development of heterotopic ossifications (HO). The second objective was to prove the hypothesis that tetraplegic patients with autonomic dysreflexia (AD) develop HO more often than patients without AD. METHODS: A retrospective analysis from 2002 to 2009 of 330 patients with spinal cord injuries was performed and led to the inclusion of 77 traumatic tetraplegic patients. Clinical data was reviewed to determine the appearance of HO (n = 8) and its possible coincidence with AD during urodynamics. Spearman's correlation coefficient was calculated to test the relationship between HO and initial AIS category or the change in AIS category within 6 weeks. A matched pair (age, neurological level of injury) analysis of two samples (n = 8 with/without appearance of HO; total n = 16) was performed. RESULTS: The appearance of HO was significantly correlated with an initial AIS A compared to incomplete tetraplegia at baseline (p < 0.017). The conversion of AIS A into incomplete tetraplegia was highly correlated with the incidence of HO (p < 0.003). AD showed a positive correlation with HO (r = 0.97, p = 0.001). CONCLUSIONS: An initial AIS A that converts early into an incomplete tetraplegia constitutes a risk factor for the development of HO. Additionally, AD constitutes an important trigger in the development of HO in acute traumatic tetraplegic patients. PMID- 26814789 TI - Erratum to: Autonomic dysreflexia: a possible trigger for the development of heterotopic ossifications after traumatic spinal cord injury? : A clinical longitudinal study. PMID- 26814790 TI - Rethinking bicycle helmets as a preventive tool: a 4-year review of bicycle injuries. AB - INTRODUCTION: Traumatic brain injury is a leading cause of disability in bicycle riders. Preventive measures including bicycle helmet laws have been highlighted; however, its protective role has always been debated. The aim of this study was to determine the utility of bicycle helmets in prevention of intra-cranial hemorrhage. We hypothesized that bicycle helmets are protective and prevent the development of intra-cranial hemorrhage. METHODS: We performed a 4-year (2009 2012) retrospective cohort analysis of all the patients who presented with traumatic brain injury due to bicycle injuries to our level 1 trauma center. We compared helmeted and non-helmeted bicycle riders for differences in the patterns of injury, need for intensive care unit admissions and mortality. RESULTS: A total of 864 patients were reviewed of which, 709 patients (helmeted = 300, non helmeted = 409) were included. Non-helmeted bicycle riders were more likely to be young (p < 0.001) males (p = 0.01). There was no difference in the median ISS between the two groups (p = 0.3). Non-helmeted riders were more likely to have a skull fracture (p = 0.01) and a scalp laceration (p = 0.01) compared to the helmeted riders. There was no difference in intra-cranial hemorrhage between the two groups (p = 0.1). Wearing a bicycle helmet was not independently associated (p = 0.1) with development of intra-cranial hemorrhage. CONCLUSION: Bicycle helmets may have a protective effect against external head injury but its protective role for intra-cranial hemorrhage is questionable. Further studies assessing the protective role of helmets for intra-cranial hemorrhage are warranted. PMID- 26814791 TI - Erratum to: Rethinking bicycle helmets as a preventive tool: a 4-year review of bicycle injuries. PMID- 26814793 TI - ESTES News 6.2014. PMID- 26814794 TI - Electrokinetic Properties of Lubricin Antiadhesive Coatings in Microfluidic Systems. AB - Lubricin is a glycoprotein found in articular joints which has long been recognized as being an important biological boundary lubricant molecule and, more recently, an impressive antiadhesive that readily self-assembles into a well ordered, polymer brush layer on virtually any substrate. The lubricin molecule possesses an overabundance of anionic charge, a property that is atypical among antiadhesive molecules, that enables its use as a coating for applications involving electrokinetic processes such as electrophoresis and electroosmosis. Coating the surfaces of silica and polymeric microfluidic devices with self assembled lubricin coatings affords a unique combination of excellent fouling resistance and high charge density that enables notoriously "sticky" biomolecules such as proteins to be used and controlled electrokinetically in the device without complications arising from nonspecific adsorption. Using capillary electrophoresis, we characterized the stability, uniformity, and electrokinetic properties of lubricin coatings applied to silica and PTFE capillaries over a range of run buffer pHs and when exposed to concentrated solutions of protein. In addition, we demonstrate the effectiveness of lubricin as a coating to minimize nonspecific protein adsorption in an electrokinetically controlled polydimethylsiloxane/silica microfluidic device. PMID- 26814792 TI - Comparison of upper limb amputees and lower limb amputees: a psychosocial perspective. AB - BACKGROUND: Amputation of limb is essential in certain conditions; however, it may have significant impact on the patient's psychological condition. The present study investigates psychological responses of upper limb (UL) amputees versus lower limb (LL) amputees regarding prosthetic adjustment, social discomfort, depression, and body image anxiety. METHODS: Traumatic major amputations of 20 upper and 38 lower extremities of 58 patients who were currently using prosthesis were included. 12 of UL amputations were of dominantly used limb. Seven of the UL amputations, and nine of the LL amputations were female. The Trinity Amputation and Prosthesis Experience Scales was used for adjustment, restriction, and satisfaction. Anxiety and depression levels were assessed using Hospital Anxiety and Depression Scale (HADS). Body image disturbance and social discomfort were assessed with Amputation Body Image Scale-Revised (ABIS-R) and Social Discomfort Score, respectively. RESULTS: 58 individuals with 20 UL and 38 LL amputations were included. Mean age of UL amputees was 44.76 +/- 12.26 and 49.1 +/- 14.3 years for LL amputees. Mean time of daily prosthesis use was 11.35 +/- 4.8 and 11.52 +/- 4.7 h, respectively. Mean time since amputation was 35.4 +/- 14.3 and 36.05 +/- 13.6 months; length of prosthesis use time was 24.8 +/- 13.4 and 23.9 +/- 15.12 months, respectively. Social adjustment and adjustment to limitation subscales had significantly higher scores in LL amputees (p < 0.001). There was statistically significant difference between mean HADS depression and anxiety scores (p < 0.001). Mean total ABIS-R score indicated significantly greater body image disturbance for UL amputees (p < 0.001). CONCLUSION: Well-adjusted LL prosthesis probably has better cosmetic appearance compared to that of UL prosthesis and perception of cosmetic appearance may be the key factor that leads to increased levels of body image anxiety and social discomfort. LEVEL OF EVIDENCE: Epidemiologic and prognostic study, level III. PMID- 26814795 TI - Using Uncertain Climate and Development Information in Health Adaptation Planning. AB - To aid health adaptation decision-making, there are increasing efforts to provide climate projections at finer temporal and spatial scales. Relying solely on projected climate changes for longer-term decisions makes the implicit assumption that sources of vulnerability other than climate change will remain the same, which is not very probable. Over longer time horizons, this approach likely over estimates the extent to which climate change could alter the magnitude and pattern of health outcomes, introducing systematic bias into health management decisions. To balance this potential bias, decision-makers also need projections of other drivers of health outcomes that are, like climate change, recognized determinants of some disease burdens. Incorporating projections via an iterative process that allows for regular updates based on new knowledge and experience has the potential to improve the utility of fine-scale climate projections in health system adaptation to climate change. PMID- 26814796 TI - Quantitative Evaluation of the Carbon Hybridization State by Near Edge X-ray Absorption Fine Structure Spectroscopy. AB - The characterization of the local bonding configuration of carbon in carbon-based materials is of paramount importance since the properties of such materials strongly depend on the distribution of carbon hybridization states, the local ordering, and the degree of hydrogenation. Carbon 1s near edge X-ray absorption fine structure (NEXAFS) spectroscopy is one of the most powerful techniques for gaining insights into the bonding configuration of near-surface carbon atoms. The common methodology for quantitatively evaluating the carbon hybridization state using C 1s NEXAFS measurements, which is based on the analysis of the sample of interest and of a highly ordered pyrolytic graphite (HOPG) reference sample, was reviewed and critically assessed, noting that inconsistencies are found in the literature in applying this method. A theoretical rationale for the specific experimental conditions to be used for the acquisition of HOPG reference spectra is presented together with the potential sources of uncertainty and errors in the correctly computed fraction of sp(2)-bonded carbon. This provides a specific method for analyzing the distribution of carbon hybridization state using NEXAFS spectroscopy. As an illustrative example, a hydrogenated amorphous carbon film was analyzed using this method and showed good agreement with X-ray photoelectron spectroscopy (which is surface sensitive). Furthermore, the results were consistent with analysis from Raman spectroscopy (which is not surface sensitive), indicating the absence of a structurally different near-surface region in this particular thin film material. The present work can assist surface scientists in the analysis of NEXAFS spectra for the accurate characterization of the structure of carbon-based materials. PMID- 26814797 TI - Dynamics of Cattle Production in Brazil. AB - Movement of livestock production within a country or region has implications for genetics, adaptation, well-being, nutrition, and production logistics, particularly in continental-sized countries, such as Brazil. Cattle production in Brazil from 1977 to 2011 was spatialized, and the annual midpoint of production was calculated. Changes in the relative production and acceleration of production were calculated and spatialized using ARCGIS(r). Cluster and canonical discriminant analyses were performed to further highlight differences between regions in terms of cattle production. The mean production point has moved from the Center of Minas Gerais State (in the southeast region) to the North of Goias State (in the Midwest region). This reflects changes in environmental factors, such as pasture type, temperature and humidity. Acceleration in production in the northern region of Brazil has remained strong over the years. More recently, "traditional" cattle-rearing regions, such as the south and southeast, showed a reduction in growth rates as well as a reduction in herd size or internal migration over the period studied. These maps showed that this movement tends to be gradual, with few regions showing high acceleration or deceleration rates. PMID- 26814798 TI - Density-induced reentrant melting of colloidal Wigner crystals. AB - Electrostatic repulsions can drive crystallization in many-particle systems. For charged colloidal systems, the phase boundaries as well as crystal structure are highly tunable by experimental parameters such as salt concentration and pH. By using projections of the colloid-ion mixture to a system of (soft) repulsive spheres and the one-component plasma (OCP), we study the hitherto unexplained experimentally observed reentrant melting of electrostatically repelling colloids upon increasing the colloid density. Our study shows that the surface chemistry should involve a competition between adsorption of cations and anions to explain the observed density-induced reentrant melting. PMID- 26814799 TI - Erratum to: Menthol Inhibits the Proliferation and Motility of Prostate Cancer DU145 Cells. PMID- 26814800 TI - Tailored Hypersound Generation in Single Plasmonic Nanoantennas. AB - Ultrashort laser pulses impinging on a plasmonic nanostructure trigger a highly dynamic scenario in the interplay of electronic relaxation with lattice vibrations, which can be experimentally probed via the generation of coherent phonons. In this Letter, we present studies of hypersound generation in the range of a few to tens of gigahertz on single gold plasmonic nanoantennas, which have additionally been subjected to predesigned mechanical constraints via silica bridges. Using these hybrid gold/silica nanoantennas, we demonstrate experimentally and via numerical simulations how mechanical constraints allow control over their vibrational mode spectrum. Degenerate pump-probe techniques with double modulation are performed in order to detect the small changes produced in the probe transmission by the mechanical oscillations of these single nanoantennas. PMID- 26814801 TI - Tinea Capitis: Mixed or Consecutive Infection with White and Violet Strains of Trichophyton violaceum: A Diagnostic or Therapeutic Challenge. AB - Tinea capitis is a common dermatophyte infection affecting scalp and hair of pre pubertal children. With introduction of Griseofulvin in 1958, there has been considerable improvement in the treatment of tinea capitis. A seven-year-old male child was brought to the dermatology clinic. He presented with diffuse white scaly patches of alopecia on scalp of one-year duration. The child was sent to the microbiology section of the National Health laboratory, Botswana for the collection of the samples. The samples consisted of scalp scrapings and few plucked hairs from the suspicious areas, which were collected by swab and scalpel blade methods. Potassium hydroxide (10% KOH) mounts were prepared for scales and hair samples. Scales were positive for fungal elements and endothrix type of perforation was seen in hair. Cultures on Sabouraud's dextrose agar (SDA) and Derm agar were incubated at 25 degrees C, which yielded white variant of Trichophyton violaceum after two weeks of incubation. T. vioaceum (white variant) grew in all the plates. After six weeks of treatment with griseofulvin, the repeat culture grew only T. violaceum (violet strain). The child showed a definite clinical improvement. PMID- 26814802 TI - More safety data: what about efficacy of sildenafil? PMID- 26814803 TI - Chest dynamics asymmetry facilitates earlier detection of pneumothorax. AB - Pneumothorax is usually diagnosed when signs of life-threatening tension pneumothorax develop. The case report describes novel data derived from miniature superficial sensors that continuously monitored the amplitude and symmetry of the chest wall tidal displacement (TDi) in a premature infant that suffered from pneumothorax. Off-line analysis of the TDi revealed slowly progressing asymmetric ventilation that could be detected 38 min before the diagnosis was made. The TDi provides novel and valuable information that can assist in early detection and decision making. PMID- 26814804 TI - Swaddling is not contraindicated in the newborn period. PMID- 26814805 TI - Using surface anatomy measurements to place umbilical catheters. PMID- 26814806 TI - Reply to Ford and Hagan. PMID- 26814808 TI - Photonic Crystal Optical Tweezers with High Efficiency for Live Biological Samples and Viability Characterization. AB - We propose and demonstrate a new optical trapping method for single cells that utilizes modulated light fields to trap a wide array of cell types, including mammalian, yeast, and Escherichia coli cells, on the surface of a two-dimensional photonic crystal. This method is capable of reducing the required light intensity, and thus minimizing the photothermal damage to living cells, thereby extending cell viability in optical trapping and cell manipulation applications. To this end, a thorough characterization of cell viability in optical trapping environments was performed. This study also demonstrates the technique using spatial light modulation in patterned manipulation of live cell arrays over a broad area. PMID- 26814809 TI - Experimental and computational evaluation of the barrier to torsional rotation in a butadiyne-linked porphyrin dimer. AB - The barrier to torsional rotation in a butadiyne-linked porphyrin dimer has been determined in solution using variable temperature UV-vis-NIR spectroscopy: DeltaH = 5.27 +/- 0.03 kJ mol(-1), DeltaS = 10.69 +/- 0.14 J K(-1) mol(-1). The value of DeltaH agrees well with theoretical predictions. Quantum chemical calculations (DFT) were used to predict the torsion angle dependence of the absorption spectrum, and to calculate the vibronic fine structure of the S0 -> S1 absorption for the planar dimer, showing that the absorption band of the planar conformer has a vibronic component overlapping with the <0|0> absorption of the perpendicular conformer. The torsion barrier in the porphyrin dimer is higher than that of 1,4-diphenylbutadiyne (calculated DeltaH = 1.1 kJ mol(-1)). Crystallographic bond lengths and IR vibrational frequencies confirm that there is a greater contribution of the cumulenic resonance form in butadiyne-linked porphyrin dimers than in 1,4-diphenylbutadiyne. The DFT frontier orbitals of the twisted conformer of the porphyrin dimer are helical, when calculated in the absence of symmetry. The helical character of these orbitals disappears when D2d symmetry is enforced in the 90 degrees twisted conformer. Helical representations of the frontier orbitals can be generated by linear combinations of the more localised orbitals from a symmetry-constrained calculation but they do not indicate pi-conjugation. This work provides insights into the relationship between electronic structure and conformation in alkyne-linked conjugated oligomers. PMID- 26814810 TI - Pollinator Competition as a Driver of Floral Divergence: An Experimental Test. AB - Optimal foraging models of floral divergence predict that competition between two different types of pollinators will result in partitioning, increased assortative mating, and divergence of two floral phenotypes. We tested these predictions in a tropical plant-pollinator system using sexes of purple-throated carib hummingbirds (Anthracothorax jugularis) as the pollinators, red and yellow inflorescence morphs of Heliconia caribaea as the plants, and fluorescent dyes as pollen analogs in an enclosed outdoor garden. When foraging alone, males exhibited a significant preference for the yellow morph of H. caribaea, whereas females exhibited no preference. In competition, males maintained their preference for the yellow morph and through aggression caused females to over visit the red morph, resulting in resource partitioning. Competition significantly increased within-morph dye transfer (assortative mating) relative to non-competitive environments. Competition and partitioning of color morphs by sexes of purple-throated caribs also resulted in selection for floral divergence as measured by dye deposition on stigmas. Red and yellow morphs did not differ significantly in dye deposition in the competition trials, but differences in dye deposition and preferences for morphs when sexes of purple-throated caribs foraged alone implied fixation of one or the other color morph in the absence of competition. Competition also resulted in selection for divergence in corolla length, with the red morph experiencing directional selection for longer corollas and the yellow morph experiencing stabilizing selection on corolla length. Our results thus support predictions of foraging models of floral divergence and indicate that pollinator competition is a viable mechanism for divergence in floral traits of plants. PMID- 26814811 TI - Spatial and temporal evolution of the epidemic of charcoal-burning suicide in Japan. AB - PURPOSE: An epidemic of carbon monoxide poisoning suicide by burning charcoal occurred in Hong Kong and Taiwan. An epidemic also emerged in Japan from February 2003 and resulted in an increase of 10-20 % in overall suicide rates in younger adults (aged <45 years) in the mid-2000s. We investigated the spatial and temporal evolution of the epidemic to assess its impact on the epidemiology of suicide in Japan. METHODS: Mortality data were obtained from the official vital statistics of Japan. Smoothed standardized mortality ratios of charcoal-burning and non-charcoal-burning suicide were estimated for the period 2003-2013 using Bayesian hierarchical models. Joinpoint regression analysis was performed to analyze secular trends in suicide rates by gender, method used and geographic location between 1999 and 2013. RESULTS: Suicide by burning charcoal rose sharply in the mid-2000s and was not accompanied by a simultaneous decline in alternative methods. The epidemic of charcoal-burning suicide in Japan showed a pronounced spatial pattern, being concentrated in rural prefectures particularly among males. For men but not women, the epidemic contributed to the widening of urban rural disparities in suicide rates (higher rates in rural areas). CONCLUSIONS: Our results differ from previous research in other Asian countries (e.g., Taiwan), where the epidemic of charcoal-burning suicide emerged more prominently in urban areas. In Japan, the introduction and diffusion of charcoal burning contributed to a real excess in suicide rates, as well as a widening of the urban/rural disparity in suicide. PMID- 26814812 TI - A mitochondrial outer membrane-localized protein encoded by White spot syndrome virus. AB - White spot syndrome virus (WSSV) is a devastating pathogen of crustaceans that causes huge losses to global shrimp farming. In this study, a mitochondrial outer membrane protein encoded by WSSV, termed as wsv152, was identified. Bioinformatics analysis showed that wsv152 shared no similarity with any known proteins. Real-time RT-PCR revealed that wsv152 was initially transcribed at 6 h post WSSV infection. Fluorescent microscopy demonstrated that the wsv152-GFP fusion protein was present in the mitochondrion. Western blot further suggested that wsv152 was specifically localized on the outer membrane of mitochondria. To our knowledge, this is the first report of a mitochondrion-localized protein encoded by WSSV. PMID- 26814813 TI - Brachypodium distachyon is a suitable host plant for study of Barley yellow dwarf virus. AB - Barley yellow dwarf viruses (BYDVs) belong to the family Luteoviridae and cause disease in cereals. Because of the large and complex genome of cereal plants, it is difficult to study host-virus interactions. In order to establish a model host system for the studies on BYDVs, we examined the susceptibility of a monocot model plant, Brachypodium distachyon, to BYDV-GAV infection. Fourteen days after BYDV-GAV inoculation by aphid transmission, B. distachyon plants (inbred line Bd21-3) showed conspicuous disease symptoms such as leaf reddening, dwarfness and root stunting. Virus accumulation was detected in both shoots and roots using reverse transcription PCR and triple antibody sandwich ELISA. Compared with infected wheat plants, B. distachyon plants developed more severe disease symptoms and accumulated a higher level of BYDV-GAV. Under transmission electron microscope, we observed that virus particles accumulated in companion cells and BYDV-GAV infection was associated with the deformation of chloroplasts in the infected leaves of B. distachyon plants. Our results suggest that B. distachyon is a suitable and promising experimental model plant for the host-BYDV-GAV pathosystem and possibly for other BYDVs. PMID- 26814814 TI - More Work Needed! Analysis of Fuzzy Concepts in Simulation-Based Learning. PMID- 26814815 TI - Validating the Japanese Self-Directed Learning Readiness Scale for Nursing Education. AB - BACKGROUND: The Self-Directed Learning Readiness Scale for Nursing Education (SDLRSNE) assesses the extent to which an individual has the characteristics, capabilities, and attitudes required for self-directed learning. This study aimed to validate the Japanese version of the SDLRSNE with graduate-level nursing students. METHOD: Confirmatory factor analyses, using data from a cross-sectional online survey of 376 nursing students, were conducted to examine construct validity. Relationships with potential related factors were analyzed to evaluate construct validity. Reliability was evaluated with item analysis and Cronbach's alpha. RESULTS: Factor analyses revealed that three-factor and individual subscale models had a moderate-to-poor fit. No meaningful relationship with potential related factors was noted. Reliability measurements indicated a moderate fit to data. CONCLUSION: This study could not confirm that the Japanese version of the SDLRSNE had acceptable levels of reliability and validity when tested with graduate-level nursing students. Further research is needed to examine the psychometric properties of the Japanese version of the SDLRSNE with other adult nursing learners or with graduate-level nursing students in other countries. PMID- 26814816 TI - Turkish Senior Nursing Students' Communication Experience With English-Speaking Patients. AB - BACKGROUND: Simulation has been widely accepted as a valuable learning method in nursing education programs so that nursing students can learn and develop communication skills. The aim of this study was to evaluate nursing students' communication experience with an English-speaking standardized patient in the context of the Rational Administration of Medicines course. METHOD: Involving both quantitative and qualitative research designs, this descriptive study was conducted with 104 nursing students in Ankara, Turkey, from September 2012 to July 2013. RESULTS: The majority (98.1%) of the participants stated the necessity of improving their English to communicate with English-speaking patients. Three overarching categories, including seven themes, emerged from the description of nursing students' experience: recognition of emotions, experiences during the simulation, and gains. CONCLUSION: Standardized patient practice emphasized the significance of cultural differences, of knowing and using a foreign language, of communication, and of patient safety. PMID- 26814817 TI - Power of Peer-Assisted Learning: An Interdisciplinary Mobility Laboratory Experience. AB - BACKGROUND: The benefits of early patient mobility in the hospital environment has been well established. This article highlights an interactive peer-assisted learning (PAL) mobility laboratory. Physical therapy (PT) students taught patient mobility skills to nursing students, with the goal of enhancing mobility knowledge and improved understanding of the two disciplines' roles and responsibilities. METHOD: The students were divided into 10 groups, with six nursing and three PT students in each group; each group rotated through the 10 mobility stations every 20 minutes. After completing all stations, the nursing students reviewed a case scenario requiring application of the recently learned knowledge and skills. RESULTS: Analysis revealed that the nursing students demonstrated significant improvement in overall knowledge of safe patient mobility, as well as improved confidence in the instruction of safe patient mobility. CONCLUSION: Both groups reported that the PAL strategy was successful in achieving the intended goals of improved interprofessional understanding. PMID- 26814818 TI - Comparison of Mental Health Characteristics and Stress Between Baccalaureate Nursing Students and Non-Nursing Students. AB - BACKGROUND: Nurses consistently report the highest levels of job stress among all health professionals. To best prepare students for such a high-stress profession, insights into the onset of stress is warranted, especially with the literature supporting that nursing students experience significant stress during their education. METHOD: This study sought to explore the sources of stress among nursing students and to compare stress levels and selected mental health indicators between nursing students and the general student body using the paper and-pencil version of the National College Health Assessment II. RESULTS: Nursing students were found to have significantly more stress, anxiety, sleep disturbances, and stress-related illnesses than the general student body. CONCLUSION: The findings highlight the importance of self-care and stress management skills education in nurse preparatory programs for use in both academic preparation and in future careers. PMID- 26814819 TI - Clinical Faculty Management of the Challenges of Being a Guest in Clinical Settings: An Exploratory Study. AB - BACKGROUND: Clinical experience is a critical component of basic nursing education. Little research has focused on the perspectives of clinical faculty (CF) who engage in practical nursing education in challenging clinical settings associated with increased patient acuity and complexity. METHOD: The aim of this qualitative study was to understand CF's perspectives of what supports and hinders their ability to foster baccalaureate nursing students' clinical education. RESULTS: Findings indicate challenges related to CF being viewed as "guests" in the clinical settings, complicating communication with nursing staff about constructive learning experiences. CF receive support from other CF to assist in balancing student priorities and developing relationships with clinical staff . CONCLUSION: CF success was linked to how well they advance the view of students and themselves as being an integral part of the nursing team. Further research is needed to understand how CF use their social capital to advance clinical nursing education. PMID- 26814820 TI - Transformative Experience: Developing Competence in Novice Nursing Faculty. AB - BACKGROUND: The nursing faculty shortage has led to an increasing number of master's-prepared clinical nurse experts becoming nursing faculty to teach prelicensure nursing students, often without adequate preparation for the complex specialized role of an academic nurse educator. METHOD: A hermeneutic phenomenological qualitative study was designed to gain insight about novice nursing faculty's experience in academia, to examine their perceptions of facilitators and barriers to the development of nurse educators' practice competence, and to identify transformative learning experiences related to novice faculty development. The data consisted of audio recordings and verbatim transcripts of interviews, along with journal data describing day-to-day experiences as novice nurse academics. Data were analyzed using Moustakas' seven step process. RESULTS: Facilitators and barriers, along with characteristics of transformative learning experiences, were identified. An essential combination of facilitating factors, mentorship, and internship programs was discovered. CONCLUSION: Internship programs are a necessary link in creating academic environments that contribute to the development of competence in novice nursing faculty. [ PMID- 26814821 TI - Reflective Journaling for Critical Thinking Development in Advanced Practice Registered Nurse Students. AB - BACKGROUND: Critical thinking, clinical decision making, and critical reflection have been identified as skills required of nurses in every clinical situation. The Educating Nurses: A Call for Radical Transformation report suggested that critical reflection is a key to improving the educational process. Reflective journaling is a tool that helps develop such skills. METHOD: This article presents the tool of reflective journaling and the use of this process by educators working with students. It describes the use of reflective journaling in graduate nursing education, as well as a scoring process to evaluate the reflection and provide feedback. RESULTS: Students and faculty found the journaling to be helpful for reflection of a clinical situation focused on critical thinking skill development. The rubric scoring tool provided faculty with a method for feedback. CONCLUSION: Reflective journaling is a tool that faculty and students can use to develop critical thinking skills for the role of the advanced practice RN. A rubric scoring system offers a consistent format for feedback. PMID- 26814822 TI - Honoring Diversity: Developing Culturally Competent Communication Skills Through Simulation. AB - BACKGROUND: Students in nursing programs must learn how to communicate with patients in a culturally competent manner. METHOD: This article explores current best practices in nursing education regarding the inclusion of diversity and cultural humility in the program of study and provides recommendations for innovative ways of thoughtfully threading cultural competence into the curriculum. RESULTS: Mastering culturally competent communication is unlike any other nursing skill, deserving of a creative way of teaching. This article describes the use of the pedagogy in simulation to create the opportunity to introduce scenarios where students care for patients of diverse backgrounds. CONCLUSION: Establishing cultural competence encompasses more than just learning about different cultures. A true emergent experience using standardized patients and scenarios highlighting the cultural considerations that nurses need to be cognizant of and comfortable with can provide a new way of teaching this relevant and current topic. PMID- 26814823 TI - Use of Visual Narrative Illustrations to Teach Pathophysiology Concepts to Nursing Students. AB - BACKGROUND: The care of patients with acute and chronic illnesses requires nurses to fully understand the underlying pathophysiology associated with disease processes. Although mastering a pathophysiology course is a strong predictor of student success in nursing programs, it is a course with which students and new nurses most often struggle. METHOD: The authors describe a teaching innovation- visual narrative illustration (VNI)--and demonstrate how VNIs are used to teach complex pathophysiology concepts to nursing students. RESULTS: The consistent positive feedback regarding the VNIs that have already been implemented in the pathophysiology course prompted the authors to systematically and formally study the impact of this innovative approach on student learning and knowledge retention. CONCLUSION: Use of VNI is an innovative teaching strategy that has the potential to augment other course materials and bridge some of the knowledge gaps that challenge nursing students from fully understanding pathophysiologic concepts. PMID- 26814824 TI - Preparing Nurse Leaders to Innovate: Iowa's Innovation Seminar. AB - BACKGROUND: Currently, no doctoral guidelines to teach innovation exist. Using Christensen's theory of disruptive innovation, the five discovery skills used by disruptive innovators provide the framework for designing a leadership development approach to enable and support a mindset to innovate. METHOD: Executive leadership students were provided with didactic content on innovation, were assigned to non-healthcare settings for an anthropological dig to uncover innovative activities, and were provided with reflective prompts to enable a new context for innovation. Faculty collaborated with other fields and took risks to provide new contexts to innovate. RESULTS: Students identified and proposed innovations for current health care issues. Some of the innovations included processes, evaluation methods, data analytics for care design, and patient engagement solutions. CONCLUSION: Faculty crossed borders for field experiences, as well as disciplinary borders. This collaborative seminar demonstrated that it is possible to develop executive nurse leaders to innovate. PMID- 26814825 TI - Learning From Errors: The Importance of Proofreading. PMID- 26814826 TI - Fishing for Pharmacology Success: Gaming as an Active Learning Strategy. PMID- 26814827 TI - Soft-shear induced phase-separated nanoparticle string-structures in polymer thin films. AB - Application of shear stress has been shown to unidirectionally orient the microstructures of block copolymers and polymer blends. In the present work, we study the phase separation of a novel nanoparticle (NP)-polymer blend thin film system under shear using a soft-shear dynamic zone annealing (DZA-SS) method. The nanoparticles are densely grafted with polymer chains of chemically dissimilar composition from the matrix polymer, which induces phase separation upon thermal annealing into concentrated nanoparticle domains. We systematically examine the influence of DZA-SS translation speed and thus the effective shear rate on nanoparticle domain elongation and compare this with the counterpart binary polymer blend behavior. Unidirectionally aligned nanoparticle string-domains are fabricated in the presence of soft-shear in confined thin film geometry. We expect this DZA-SS method to be applicable to various NP-polymer blends towards unidirectionally aligned nanoparticle structures, which are important to functional nanoparticle structure fabrication. PMID- 26814828 TI - Development of Mag-FMBO in clay-reinforced KGM aerogels for arsenite removal. AB - To seek high-efficient, convenient and robust methods to decontaminate water polluted by arsenite are critically in demand. Here, we developed a series of magnetic konjac glucomannan (KGM) aerogels as adsorbents for arsenite removal. These adsorbents were fabricated based on sodium montmorillonite (Na(+)-MMT) reinforced KGM matrix with magnetic Fe and Mn oxides (Mag-FMBO) inside. The obtained aerogels adsorbents were characterized by using compression test, thermo gravimetric analysis (TGA), vibrating sample magnetometer (VSM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The characteristic results showed that the composite aerogels possessed strong mechanical and magnetic property, excellent thermal characteristic and tunable pore structure. Batch adsorption tests were used to evaluate arsenite removal capacity. The adsorption results exhibited that the arsenite removal process was pH-dependent, followed a pseudo-second-order rate equation and Langmuir monolayer adsorption. The maximum arsenite uptake capacity of magnetic aerogels M1.5 reached 16.03mgg(-1) according to Langmuir isotherm at pH 7 and 323K. Besides, the magnetic composite aerogels can be repeatedly used after the treatment of regenerant (NaOH/NaCl/NaClO solution). PMID- 26814829 TI - Quantitatively analyzing the mechanism of giant circular dichroism in extrinsic plasmonic chiral nanostructures by tracking the interplay of electric and magnetic dipoles. AB - Plasmonic chirality has drawn much attention because of tunable circular dichroism (CD) and the enhancement for chiral molecule signals. Although various mechanisms have been proposed to explain the plasmonic CD, a quantitative explanation like the ab initio mechanism for chiral molecules, is still unavailable. In this study, a mechanism similar to the mechanisms associated with chiral molecules was analyzed. The giant extrinsic circular dichroism of a plasmonic splitting rectangle ring was quantitatively investigated from a theoretical standpoint. The interplay of the electric and magnetic modes of the meta-structure is proposed to explain the giant CD. We analyzed the interplay using both an analytical coupled electric-magnetic dipole model and a finite element method model. The surface charge distributions showed that the circular current yielded by the splitting rectangle ring causes the ring to behave like a magneton at some resonant modes, which then interact with the electric modes, resulting in a mixing of the two types of modes. The strong interplay of the two mode types is primarily responsible for the giant CD. The analysis of the chiral near-field of the structure shows potential applications for chiral molecule sensing. PMID- 26814830 TI - Activation of Autophagy by Everolimus Confers Hepatoprotection Against Ischemia Reperfusion Injury. AB - As the criteria for liver donation have been extended to include marginal donors, liver grafts are becoming particularly vulnerable to hepatic ischemia-reperfusion injury (IRI). However, no specific measures have been validated to ameliorate hepatic IRI. In this article, we explored whether everolimus has protective effects against hepatic IRI in relation with autophagy. The effects of everolimus were investigated in both in vitro and in vivo hepatic IRI models. Mouse hepatocyte AML12 cells and BALB/c mice were utilized for the establishment of each model. In the IRI-induced AML12 cells, everolimus treatment increased the expressions of autophagic markers (microtubule-associated protein 1 light chain 3 and p62) and decreased pro-apoptotic proteins (cleaved caspase 3 and cleaved poly ADP ribose polymerase). The blockage of autophagy, using either bafilomycin A1 or si-autophagy-related protein 5, abrogated these anti-apoptosis effects of everolimus. Subsequently, everolimus administration to the hepatic IRI-induced mice provided hepatoprotective effects in terms of (1) decreasing the expressions of pro-apoptotic proteins, (2) inhibiting the release of pro-inflammatory cytokines (IL-6 and tumor necrosis factor-alpha), (3) reducing elevated liver enzymes (aspartate transaminase, alanine transaminase, and ammonia), and (4) restoring liver histopathology. These findings suggest that everolimus protects the liver against hepatic IRI by way of activating autophagy, and thus could be a potential therapeutic agent for hepatic IRI. PMID- 26814831 TI - Reasons for Treatment Choices in Knee and Hip Osteoarthritis: A Qualitative Study. AB - OBJECTIVE: Conservative treatment modalities in osteoarthritis (OA) of the hip or knee are underused, whereas the demand for surgery is rising substantially. To improve the use of conservative treatment modalities, a more in-depth understanding of the reasons for patients' treatment choices is required. This study identifies the reasons for choice of treatment in patients with hip or knee OA. METHODS: Semistructured in-depth interviews with 24 OA patients were held. Stratified purposive sampling was used to enrich data variation. Interviews were transcribed verbatim and subsequently coded using a thematic approach. Two independent researchers reflected on, compared, discussed, and adjusted the coding. RESULTS: Various treatment modalities were discussed by respondents: medication, exercise, physical therapy, injections, surgery, complementary, and alternative treatment. Four key themes underlying the choice for or against a treatment modality for OA were identified: 1) treatment characteristics: expectations about its effectiveness and risks, the degree to which it can be personalized to a patient's needs and wishes, and the accessibility of a treatment; 2) personal investment in terms of money and time; 3) personal circumstances: age, body weight, comorbidities, and previous experience with a treatment; and 4) support and advice from the patient's social environment and health care providers. CONCLUSION: The 4 identified key themes enhance the insight of health care providers into the widespread reasons influencing patients' treatment choices for knee or hip OA. This knowledge can be used in clinical practice to aid shared decision making, which may lead to optimized treatment choices for both conservative and surgical treatment. PMID- 26814832 TI - Host-Sensitized NIR Quantum Cutting Emission in Nd(3+) Doped GdNbO4 Phosphors and Effect of Bi(3+) Ion Codoping. AB - Host-sensitized near-infrared quantum cutting (QC) emission has been demonstrated in Nd(3+) doped Gd(1-x)Nd(x)NbO4 phosphors for various x values. Further, the effect of Bi(3+) ion addition as a sensitizer on near-infrared QC is studied in detail. X-ray diffraction confirms a monoclinic structure for pure and Nd(3+) doped phosphors. Pulsed laser excitation at 266 nm of Gd(1-x)Nd(x)NbO4 and Gd(0.99-x)Nd(x)Bi(0.01)NbO4 causes efficient room-temperature energy transfer from the NbO4(3-) to the Nd(3+) ions and the NbO4(3-) and Bi(3+) ions to the Nd(3+) ions, respectively, which emits more than one near-infrared photon for single impinging ultraviolet photon. The emission band of Nd(3+) shows unusual character where the intensity of the (4)F(3/2)-(4)I(9/2) transition at 888 nm is higher than the intensity of the transition (4)F(3/2)-(4)I(11/2) at 1064 nm, due to energy transfer from GdNbO4 host to Nd(3+) ion. Using photoluminescence lifetime studies, the quantum cutting efficiencies are found to be the maximum 166% and 172% for Gd(0.95)Nd(0.05)NbO4 and Gd(0.94)Nd(0.05)Bi(0.01)NbO4, respectively. The present study could establish Nd(3+) ion as an alternative of Yb(3+) ion for near-infrared quantum cutting. This work facilitates the probing of Nd(3+) ions doped phosphor materials for next generation Si-solar cells. PMID- 26814833 TI - Reply. PMID- 26814834 TI - Gaining perspective on own illness - the lived experiences of a patient education programme for women with treated coeliac disease. AB - AIMS AND OBJECTIVES: To explore the lived experiences of women with coeliac disease after attending a patient education programme, to gain a broader perspective of its influence. BACKGROUND: Adults, particularly women, with coeliac disease report suffering from poor well-being and reduced quality of life in terms of health. Patient education programmes might support and encourage them in the search for possible improvements in lifestyle and in their approach to the disease. DESIGN: A qualitative phenomenological study. METHODS: Personal narrative interviews with 14 women suffering from coeliac disease who had participated in an educational programme. Data analysis in accordance with Giorgi was performed. RESULTS: The essential structure of women's lived experiences following their participation in the patient education programme was found to be an interaction with others with the same disease, which left the women feeling individually strengthened. The interaction enabled the participants to acquire a broader view of their life with coeliac disease. As a result, this realigned their sense of self in relation to their own disease. CONCLUSION: In coping with coeliac disease, it seems that women need interaction with others with the disease to experience togetherness within a group, get the opportunity to compare themselves with others and to exchange knowledge. The interaction appears to result in that women acquire an overview of life with the disease, develop a greater confidence and dare to try new things in life. RELEVANCE TO CLINICAL PRACTICE: When designing a patient education programme it seems important to consider the needs of persons to meet others with the same disease, and to ask them about their need for knowledge, rather than simply assuming that health care professionals know what they need. PMID- 26814835 TI - Interlaboratory Evaluation of Ultraviolet Radiation Emissions from Compact Fluorescent Lamps. AB - There have been many recent reports regarding the potential risks of UV emissions from compact fluorescent lamps (CFLs). In some of these reports, the robustness of the measurements was difficult to discern. We conducted round-robin measurements, involving three lamp manufacturers and two government research laboratories to gather reliable data on the UV emissions from commercially available CFLs. The initial sample of lamps consisted of 71 spiral-shaped CFLs purchased from local retailers. From the initial sample, 14 "high UV emitting" CFLs were chosen for further evaluation. We compared the UV emissions at a distance of 20 cm with the UV exposure limits (ELs) published by the International Commission on Non-ionizing Radiation Protection (ICNIRP). We found that the allowable exposure time for measured lamps ranged from 21 to 415 h. This indicates that the emissions would not exceed the short-term ELs that have been established by the ICNIRP for healthy individuals. We also evaluated the potential long-term risk and found it to be insignificant. There was a large variation in the UV emissions found, even for lamps from a single package, indicating that it is impossible to predict the UV output of a CFL based on its physical appearance and model designation. PMID- 26814836 TI - Quality of life and physical activity levels in outpatients with schizophrenia. AB - OBJECTIVES: To assess quality of life (QoL) and physical activity (PA) levels of outpatients with schizophrenia and healthy controls matched for age, gender, body mass index (BMI), hip circumference, waist circumference, and waist-to-hip ratio. Additionally, the present study investigated associations between PA levels, QoL, and anthropometric and behavioral measures among outpatients with schizophrenia. METHODS: Thirty-two outpatients with schizophrenia and 32 individuals without mental illness were included in the study. QoL and PA levels were assessed by the World Health Organization Quality of Life Instrument - Abbreviated version (WHOQOL-Bref) and by GT3X triaxial accelerometers, respectively. RESULTS: Outpatients with schizophrenia had poorer QoL and lower vigorous PA levels compared with healthy controls (p < 0.05). The group with schizophrenia showed a significant association between higher weight and lower scores in the mental health domain of the WHOQOL-Bref. A higher BMI was also significantly associated with lower scores in the physical health domain of the WHOQOL-Bref. Schizophrenic patients with smoking behaviors were associated with fewer steps per day and with less moderate to vigorous PA. CONCLUSIONS: This study seeks to shed some light upon the lifestyle of patients with schizophrenia. New psychosocial approaches should focus on PA, weight, and smoking management, thereby helping these patients to improve their QoL. PMID- 26814837 TI - Hair cortisol in drug-naive first-episode individuals with psychosis. AB - OBJECTIVES: To compare hair cortisol concentrations (HCC) in drug-naive first episode psychosis (FEP) patients and healthy controls and to investigate the correlations between HCC and psychopathology. METHODS: Twenty-four drug-naive FEP patients and 27 gender- and age-matched healthy control subjects were recruited. The Structured Clinical Interview for DSM-IV (SCID-1) was used to confirm/rule out diagnoses, and the Positive and Negative Symptoms Scale (PANSS) was used to assess symptom severity. Hair samples (2-3 cm long) obtained from the posterior vertex region of the scalp were processed in 1-cm segments considering a hair growth rate of 1 cm per month. The 1-cm segments were classified according to their proximity to the scalp: segment A was the closest to the scalp and referred to the month prior to inclusion in the study. Segments B and C referred to the 2nd and 3rd months prior to the time of evaluation respectively. Hair steroid extraction was performed using a known protocol. RESULTS: Two-way analysis of covariance (ANCOVA) with gender and age as covariates revealed a group effect (F1.106 = 4.899, p = 0.029) on HCC. Between-segment differences correlated with total PANSS score and with PANSS General Psychopathology subscale and total score. CONCLUSIONS: Our findings suggest that hypothalamic-pituitary-adrenal (HPA) axis, as assessed by long-term (3-month) cortisol concentration, is abnormal in the early stages of psychosis. The magnitude of changes in HCC over time prior to the FEP correlates to psychopathology. HPA axis abnormalities might begin prior to full-blown clinical presentation requiring hospital admission. PMID- 26814838 TI - Diversity and Biogeography of Bathyal and Abyssal Seafloor Bacteria. AB - The deep ocean floor covers more than 60% of the Earth's surface, and hosts diverse bacterial communities with important functions in carbon and nutrient cycles. The identification of key bacterial members remains a challenge and their patterns of distribution in seafloor sediment yet remain poorly described. Previous studies were either regionally restricted or included few deep-sea sediments, and did not specifically test biogeographic patterns across the vast oligotrophic bathyal and abyssal seafloor. Here we define the composition of this deep seafloor microbiome by describing those bacterial operational taxonomic units (OTU) that are specifically associated with deep-sea surface sediments at water depths ranging from 1000-5300 m. We show that the microbiome of the surface seafloor is distinct from the subsurface seafloor. The cosmopolitan bacterial OTU were affiliated with the clades JTB255 (class Gammaproteobacteria, order Xanthomonadales) and OM1 (Actinobacteria, order Acidimicrobiales), comprising 21% and 7% of their respective clades, and about 1% of all sequences in the study. Overall, few sequence-abundant bacterial types were globally dispersed and displayed positive range-abundance relationships. Most bacterial populations were rare and exhibited a high degree of endemism, explaining the substantial differences in community composition observed over large spatial scales. Despite the relative physicochemical uniformity of deep-sea sediments, we identified indicators of productivity regimes, especially sediment organic matter content, as factors significantly associated with changes in bacterial community structure across the globe. PMID- 26814839 TI - Dynamic Regulation of AMPAR Phosphorylation In Vivo Following Acute Behavioral Stress. AB - The tuning of glutamatergic transmission is an essential mechanism for neuronal communication. alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are ionotropic glutamate receptors that mediate fast synaptic transmission. The phosphorylation states of specific serine residues on the GluA1 and GluA2 AMPAR subunits are considered critical post-translational modifications that regulate AMPAR activity and subcellular trafficking. While behavioral stress, via stress hormones, exerts specific alterations on such glutamatergic processes, there have been conflicting data concerning the influence of stress on AMPAR phosphorylation in different brain regions, and the post-stress signaling mechanisms mediating these processes are not well delineated. Here, we examined the dynamics of phosphorylation at three AMPAR serine residues (ser831-GluA1, ser845-GluA1, and ser880-GluA2) in four brain regions [amygdala, medial prefrontal cortex (mPFC), dorsal hippocampus, and ventral hippocampus] of the rat during the hour following behavioral stress. We also tested the impact of post stress corticosteroid receptor blockade on AMPAR phosphorylation. Both GluA1 subunit residues exhibited elevated phosphorylation after stress, yet post-stress administration of corticosteroid receptor antagonists curtailed these effects only at ser831-GluA1. In contrast, ser880-GluA2 displayed a time-dependent tendency for early decreased phosphorylation (that was selectively augmented by mifepristone treatment in the amygdala and mPFC of stressed animals) followed by increased phosphorylation later on. These findings show that the in vivo regulation of AMPAR phosphorylation after stress is a dynamic and subunit specific process, and they provide support for the hypothesis that corticosteroid receptors have an ongoing role in the regulation of ser831-GluA1 phosphorylation during the post-stress interval. PMID- 26814840 TI - Respiratory gating algorithm helps to reconstruct more accurate electroanatomical maps during atrial fibrillation ablation performed under spontaneous respiration. AB - PURPOSE: Electroanatomical mapping is a useful tool during the ablation of atrial fibrillation. Respiratory movement might influence the mapping accuracy and merging. This study aims to investigate the effect of respiratory gating on the accuracy of magnetic-field-based electroanatomical mapping under spontaneous respiration. METHODS: Fifty-one consecutive patients (35 male, aged 30-78 years) who underwent left atrial radiofrequency catheter ablation due to atrial fibrillation were included. Electroanatomical mapping was performed with CARTO 3 System under conscious sedation. Respiratory gating was achieved with the AccuResp algorithm (Biosense Webster). Average surface match and maximum distance of the pre-acquired and electroanatomical maps, as well as left atrial volume, were recorded with and without respiratory gating after merging. RESULTS: The average surface match of the electroanatomical map with the left atrial reconstruction was significantly better with respiratory gating than without using the algorithm (3.81 +/- 1.09 vs 4.11 +/- 1.61 mm, p = 0.0119). It was not dependent of the rhythm during mapping or the image modality used for left atrial reconstruction. The maximal distance between the two maps did not depend on the use of the algorithm (19.81 +/- 6.24 mm for gated and 20.87 +/- 7.99 mm for non gated, p = 0.3161). Left atrial volume of the map was significantly lower when using the respiratory compensation module (106.3 +/- 31.6 vs 127.0 +/- 36.4 ml, p < 0.0001) and showed a significant correlation with the pre-recorded 3D reconstruction volumes (r = 0.66, p < 0.0001). CONCLUSIONS: The use of the novel respiratory gating algorithm might improve the accuracy of electroanatomical mapping during left atrial ablation under conscious sedation. The possible impact on the effectiveness of the ablation needs to be further evaluated. PMID- 26814841 TI - The application of Big Data in medicine: current implications and future directions. AB - Since the mid 1980s, the world has experienced an unprecedented explosion in the capacity to produce, store, and communicate data, primarily in digital formats. Simultaneously, access to computing technologies in the form of the personal PC, smartphone, and other handheld devices has mirrored this growth. With these enhanced capabilities of data storage and rapid computation as well as real-time delivery of information via the internet, the average daily consumption of data by an individual has grown exponentially. Unbeknownst to many, Big Data has silently crept into our daily routines and, with continued development of cheap data storage and availability of smart devices both regionally and in developing countries, the influence of Big Data will continue to grow. This influence has also carried over to healthcare. This paper will provide an overview of Big Data, its benefits, potential pitfalls, and the projected impact on the future of medicine in general and cardiology in particular. PMID- 26814842 TI - Label-free fluorescent catalytic biosensor for highly sensitive and selective detection of the ferrous ion in water samples using a layered molybdenum disulfide nanozyme coupled with an advanced chemometric model. AB - In this work, we developed a novel layered molybdenum disulfide (MoS2) nanosheet peroxidase mimetic-based fluorescent catalytic biosensor for the sensitive and selective detection of Fe(2+). It was found that Fe(2+) remarkably enhanced the catalytic activity of the MoS2 nanosheet for oxidation of OPD to form a highly fluorescent substance, 2,3-diaminophenazine (DAPN), and the MoS2/OPD/H2O2 biosensor displayed substantial fluorescence enhancement after addition of Fe(2+) in a concentration-dependent manner. The fluorescence intensity was proportional to the concentration of Fe(2+) over a range of 0.005-0.20 MUM with a limit of detection of 3.5 nM (signal/noise = 3). When compared with the OPD/H2O2 biosensor, the MoS2/OPD/H2O2 biosensor provided a higher sensitivity and selectivity for Fe(2+), suggesting the validity of the use of the MoS2 nanosheets. To further demonstrate the feasibility of the MoS2/OPD/H2O2 biosensor for Fe(2+) detection in real water samples, we measured the three-dimensional excitation-emission spectra of the real system, and submitted the excitation emission matrix (EEM) data to an advanced chemometrics model based on parallel factor analysis (PARAFAC). The results showed that the use of the PARAFAC model could further enhance the selectivity of the biosensor and determine Fe(2+) concentration in the presence of unexpected interferents from real water samples. This work opens up new opportunities for the use of the catalytic properties of the MoS2 nanosheets and advanced chemometrics models in the field of biosensors. PMID- 26814844 TI - Cause and prevention of demyelination in a model multiple sclerosis lesion. AB - OBJECTIVE: Demyelination is a cardinal feature of multiple sclerosis, but it remains unclear why new lesions form, and whether they can be prevented. Neuropathological evidence suggests that demyelination can occur in the relative absence of lymphocytes, and with distinctive characteristics suggestive of a tissue energy deficit. The objective was to examine an experimental model of the early multiple sclerosis lesion and identify pathogenic mechanisms and opportunities for therapy. METHODS: Demyelinating lesions were induced in the rat spinal dorsal column by microinjection of lipopolysaccharide, and examined immunohistochemically at different stages of development. The efficacy of treatment with inspired oxygen for 2 days following lesion induction was evaluated. RESULTS: Demyelinating lesions were not centered on the injection site, but rather formed 1 week later at the white-gray matter border, preferentially including the ventral dorsal column watershed. Lesion formation was preceded by a transient early period of hypoxia and increased production of superoxide and nitric oxide. Oligodendrocyte numbers decreased at the site shortly afterward, prior to demyelination. Lesions formed at a site of inherent susceptibility to hypoxia, as revealed by exposure of naive animals to a hypoxic environment. Notably, raising the inspired oxygen (80%, normobaric) during the hypoxic period significantly reduced or prevented the demyelination. INTERPRETATION: Demyelination characteristic of at least some early multiple sclerosis lesions can arise at a vascular watershed following activation of innate immune mechanisms that provoke hypoxia, and superoxide and nitric oxide formation, all of which can compromise cellular energy sufficiency. Demyelination can be reduced or eliminated by increasing inspired oxygen to alleviate the transient hypoxia. PMID- 26814845 TI - Scalable improvement of SPME multipolar electrostatics in anisotropic polarizable molecular mechanics using a general short-range penetration correction up to quadrupoles. AB - We propose a general coupling of the Smooth Particle Mesh Ewald SPME approach for distributed multipoles to a short-range charge penetration correction modifying the charge-charge, charge-dipole and charge-quadrupole energies. Such an approach significantly improves electrostatics when compared to ab initio values and has been calibrated on Symmetry-Adapted Perturbation Theory reference data. Various neutral molecular dimers have been tested and results on the complexes of mono- and divalent cations with a water ligand are also provided. Transferability of the correction is adressed in the context of the implementation of the AMOEBA and SIBFA polarizable force fields in the TINKER-HP software. As the choices of the multipolar distribution are discussed, conclusions are drawn for the future penetration-corrected polarizable force fields highlighting the mandatory need of non-spurious procedures for the obtention of well balanced and physically meaningful distributed moments. Finally, scalability and parallelism of the short range corrected SPME approach are addressed, demonstrating that the damping function is computationally affordable and accurate for molecular dynamics simulations of complex bio- or bioinorganic systems in periodic boundary conditions. PMID- 26814846 TI - Comorbidity of Headache and Depression After Mild Traumatic Brain Injury. AB - OBJECTIVE: To examine headache and depression over time in individuals who sustained mild traumatic brain injury (mTBI). Prevalence of headache and depression early after mTBI and at 1 year postinjury as well as the relationship between the two are evaluated. BACKGROUND: Headache is the most common physical symptom and depression is among the most common psychiatric diagnosis after traumatic brain injury regardless of severity. Headache and depression have been found to be two independent factors related to poor outcome after mTBI, yet there appears to be a paucity of research exploring the comorbidity of these two conditions after injury. METHOD/DESIGN: Longitudinal survey design over 1 year of 212 participants with mTBI who were admitted to a Level 1 trauma center for observation or other system injuries. Depression was based on a score >=10 on the Patient Health Questionnaire-9. Headache was based on participant report of new or worse-than-preinjury headache since hospitalization (baseline) or within the previous 3 months at 1 year postinjury. RESULTS: The prevalence of headache and depression at baseline was 64% (135/212) and 15% (31/212), respectively. The prevalence of headache and depression at 1 year was 68% (127/187) and 27% (50/187), respectively. The co-occurrence of headache and depression increased from 11% (23/212) at baseline to 25% (46/187) at 1 year. At 1 year, the risk ratio of individuals who had headache to be depressed was 5.43 (95% CI 2.05 14.40) compared to those without headache (P < .001). The corresponding risk ratio at baseline was 1.64 (95% CI .77-3.49; P = .23). CONCLUSIONS: While prevalence of headache is consistently high over the first year after injury, rate of depression increased over the first year for those who were followed. Given the high rate of comorbidity, those with headache may develop depression over time. Evaluation for possible depression in those with headache after mTBI should be conducted to address both conditions over the year following injury. PMID- 26814848 TI - Undescended testis and infertility-Is hormonal therapy indicated? AB - PURPOSE: The purpose of this chapter is to review hormonal therapy in cryptorchidism in boys to improve fertility. METHODS: Multiple searches, primarily in PubMed, were performed using various combinations of the terms: cryptorchidism, undescended testis (UDT), hormonal therapy, fertility, infertility, germ cell numbers, spermatogonia and semen analyses. In additions the pertinent articles from the reference lists in these papers were also obtained and reviewed. RESULTS: Data on fertility in unilateral cryptorchidism does not reveal a significant risk for infertility. Testes biopsies in childhood do not correlate with fertility parameters in adulthood. In bilateral cryptorchidism there is a significant risk of infertility. Results of hormonal treatment were not reported separately for bilateral cryptorchidism. Current data is insufficient to know if hormonal therapy is efficacious in bilateral UDT. CONCLUSIONS: Hormonal therapy should not be used in childhood to improve fertility in cases of unilateral cryptorchidism. Testes biopsies in childhood to identify those at risk for infertility should not be performed in unilateral cryptorchidism. More data are needed to answer whether hormonal therapy is beneficial in bilateral UDT. There is insufficient data to establish that testis biopsies are helpful in bilateral cryptorchidism in identifying the subgroup with risk for infertility. They should not be performed in the routine clinical setting but may have a role in a research protocol. PMID- 26814847 TI - Predicting and verifying outcome of Tripterygium wilfordii Hook F. based therapy in rheumatoid arthritis: from open to double-blinded randomized trial. AB - Tripterygium wilfordii Hook F. (TwHF) based therapy has been proved as effective in treating rheumatoid arthritis (RA), yet the predictors to its response remains unclear. A two-stage trial was designed to identify and verify the baseline symptomatic predictors of this therapy. 167 patients with active RA were enrolled with a 24-week TwHF based therapy treatment and the symptomatic predictors were identified in an open trial; then in a randomized clinical trial (RCT) for verification, 218 RA patients were enrolled and classified into predictor positive (P+) and predictor negative (P-) group, and were randomly assigned to accept the TwHF based therapy and Methotrexate and Sulfasalazine combination therapy (M) for 24 weeks, respectively. Five predictors were identified (diuresis, excessive sweating, night sweats for positive; and yellow tongue coating, thermalgia in the joints for negative). In the RCT, The ACR 20 responses were 82.61% in TwHF/P+ group, significantly higher than that in TwHF/P- group (P = 0.0001) and in M&S/P+ group (P < 0.05), but not higher than in M&S/P- group. Similar results were yielded in ACR 50 yet not in ACR 70 response. No significant differences were detected in safety profiles among groups. The identified predictors enable the TwHF based therapy more efficiently in treating RA subpopulations. PMID- 26814850 TI - Indigenous Healing Knowledge and Infertility in Indonesia: Learning about Cultural Safety from Sasak Midwives. AB - In this article I demonstrate what can be learned from the indigenous healing knowledge and practices of traditional Sasak midwives on Lombok island in eastern Indonesia. I focus on the treatment of infertility, contrasting the differential experiences of Sasak women when they consult traditional midwives and biomedical doctors. Women's and midwives' perspectives provide critical insight into how cultural safety is both constituted and compromised in the context of reproductive health care. Core components of cultural safety embedded in the practices of traditional midwives include the treatment of women as embodied subjects rather than objectified bodies, and privileging physical contact as a healing modality. Cultural safety also encompasses respect for women's privacy and bodily dignity, as well as two-way and narrative communication styles. Local understandings of cultural safety have great potential to improve the routine practices of doctors, particularly in relation to doctor-patient communication and protocols for conducting pelvic exams. PMID- 26814851 TI - Out-of-Plane Alignment of Er(trensal) Easy Magnetization Axes Using Graphene. AB - We have studied Er(trensal) single-ion magnets adsorbed on graphene/Ru(0001), on graphene/Ir(111), and on bare Ru(0001) by scanning tunneling microscopy and X-ray absorption spectroscopy. On graphene, the molecules self-assemble into dense and well-ordered islands with their magnetic easy axes perpendicular to the surface. In contrast, on bare Ru(0001), the molecules are disordered, exhibiting only weak directional preference of the easy magnetization axis. The perfect out-of-plane alignment of the easy axes on graphene results from the molecule-molecule interaction, which dominates over the weak adsorption on the graphene surface. Our results demonstrate that the net magnetic properties of a molecular submonolayer can be tuned using a graphene spacer layer, which is attractive for hybrid molecule-inorganic spintronic devices. PMID- 26814849 TI - Differential Methylation as a Biomarker of Response to Etanercept in Patients With Rheumatoid Arthritis. AB - OBJECTIVE: Biologic drug therapies represent a huge advance in the treatment of rheumatoid arthritis (RA). However, very good disease control is achieved in only 30% of patients, making identification of biomarkers of response a research priority. We undertook this study to test our hypothesis that differential DNA methylation patterns may provide biomarkers predictive of response to tumor necrosis factor inhibitor (TNFi) therapy in patients with RA. METHODS: An epigenome-wide association study was performed on pretreatment whole blood DNA from patients with RA. Patients who displayed good response (n = 36) or no response (n = 36) to etanercept therapy at 3 months were selected. Differentially methylated positions were identified using linear regression. Variance of methylation at differentially methylated positions was assessed for correlation with cis-acting single-nucleotide polymorphisms (SNPs). A replication experiment for prioritized SNPs was performed in an independent cohort of 1,204 RA patients. RESULTS: Five positions that were differentially methylated between responder groups were identified, with a false discovery rate of <5%. The top 2 differentially methylated positions mapped to exon 7 of the LRPAP1 gene on chromosome 4 (cg04857395, P = 1.39 * 10(-8) and cg26401028, P = 1.69 * 10(-8) ). The A allele of the SNP rs3468 was correlated with higher levels of methylation for both of the top 2 differentially methylated positions (P = 2.63 * 10(-7) and P = 1.05 * 10(-6) , respectively). Furthermore, the A allele of rs3468 was correlated with European League Against Rheumatism nonresponse in the discovery cohort (P = 0.03; n = 56) and in the independent replication cohort (P = 0.003; n = 1,204). CONCLUSION: We identify DNA methylation as a potential biomarker of response to TNFi therapy, and we report the association between response and the LRPAP1 gene, which encodes a chaperone of low-density lipoprotein receptor related protein 1. Additional replication experiments in independent sample collections are now needed. PMID- 26814852 TI - [Differences in diet intake frequency of adults: findings from half a million people in 10 areas in China]. AB - OBJECTIVE: To describe the differences in diet intake frequency of adults in 10 areas surveyed by China Kadoorie Biobank (CKB) project. METHODS: CKB project recruited voluntary residents aged 30-79 years from 5 urban areas and 5 rural areas in China. The baseline survey was conducted among 512 891 eligible subjects during 2004-2008. The intake frequencies of 12 food groups were assessed through in-person interviews and analyzed. The results were adjusted for age and sex structure of the study population. RESULTS: Rice was the main cereal consumed every day in urban areas (99.0%) and rural areas (99.9%) in southern China, while wheat was the main cereal consumed every day in rural areas (99.0%) and Qingdao (88.4%) in northern China. Most subjects in Henan (98.8%) consumed other staple food every day. The lowest proportion of daily intake of fresh vegetables was observed in Gansu (74.0%) . In both southern and northern areas, urban subjects had higher proportions of daily intakes of fresh fruits, preserved vegetables, and meat than rural subjects. Similar results were found when comparing the proportions of intakes of poultry and fish/seafood at least 1 day every week. Contrast to southern China (urban: 6.5%, rural: 6.9%) , the proportions of daily intake of fresh eggs were higher in both urban areas (37.1%) and rural areas (14.6%) in northern China. The highest proportions of daily intake of soybean products and dairy products were observed in Harbin (10.0%) and Qingdao (34.3%). CONCLUSION: The intake of cereal, fresh eggs and soybean products differed between the south and the north of China. The intake of meat, poultry, fish/seafood, fresh fruits, preserved vegetables and dairy products varied considerably between urban areas and rural areas. PMID- 26814853 TI - [Investigation and analysis on current status of smoking cessation clinics in China]. AB - OBJECTIVE: To understand the current status of smoking cessation clinics in China, and provide evidence for tobacco control in the future. METHODS: A questionnaire survey through telephone interview was conducted among 201 smoking cessation clinics in China in 2013, in addition, face-to-face questionnaire surveys were conducted in 6 smoking cessation clinics and among 398 smokers in Beijing. SPSS 19.0 Software was used for the data analysis. RESULTS: A total of 94 smoking cessation clinics were still in operation in China, in which 51% belonged to the department of respiratory diseases in hospitals. Averagely, there were 3.24 doctors or nurses in each clinic, and the average weekly clinic admission was 6.92 smokers in recent months. The face to face interview indicated that one month quit rate was above 50%. Among smokers surveyed, 48% were aware of cessation clinics and 21.9% would go to clinics if they want to stop smoking. The reason for which smokers didn' t choose clinics was that they didn' t believe tobacco dependence was a disease. CONCLUSION: The number of smoking cessation clinics decreased obviously in China. Government and hospitals should take joint action to improve the awareness and acceptance of smoking cessation clinic among the public, establish comprehensive referral system, and improve the cessation intervention capacity of public health providers. PMID- 26814854 TI - [Prevalence of deliberate self-harm and its relation with suicidal behaviors among students in middle schools in Beijing]. AB - OBJECTIVE: To understand the prevalence of deliberate self-harm in middle school students in Beijing, and explore the relationship between self-harm and suicidal behaviors. METHODS: An anonymous self-administered questionnaire survey was conducted among 5 807 students selected through cluster random sampling from grade 9 to grade 12 in 16 middle schools in Beijing. RESULTS: Among the surveyed middle school students, 35.6% reported that they once had self-harm behaviors, 7.0% reported often had self-harm behaviors in the past 30 days before the survey. More girls reported self-harm behaviors than boys did. And the prevalence of self-harm behaviors was highest in girls in grade 8 and in boys in grade 9. The students in key senior high schools, or living with single or remarried parents were the risk population to have self-harm behaviors. Higher suicide behavior reporting rate was correlated with higher self-harm behavior reporting rate. Compared with students who reported no self-harm behaviors during the past month, the suicide behavior reporting rate in students reporting self-harm behaviors increased by 5.7-12.3 times. CONCLUSION: Deliberate self-harm behaviors were associated with suicide behaviors among middle school students in Beijing. Early psychological intervention and life education should be carried out among middle school students in order to find risk population and save their life. PMID- 26814855 TI - [Epidemiological survey of cerebrovascular disease among population in Inner Mongolia autonomous region]. AB - OBJECTIVE: To understand the epidemiological characteristics of cerebrovascular disease among population in Inner Mongolia. METHODS: From September 2013 to January 2014, a total of 19 315 local residents in all age groups were selected through cluster random sampling, and face to face questionnaire survey was conducted among them, than health examination was provided for them. RESULTS: The overall prevalence of cerebrovascular diseases among the population in all age group was 1 812.06/100 000 (2 008.86/100 000 in males and 1 613.24/100 000 in females). The prevalence of cerebrovascular diseases increased with age, and the prevalence was higher in males than in females, in rural population than in urban population and in people with lower educational level than in people with higher educational level. The annual incidence stroke was 392.54/100 000, the difference in the incidence between males and females had no statistical significance (chi(2)=0.380, P=0.846). The incidence of stroke was higher in rural population than in urban population, the difference was statistically significant (chi(2)=13.029, P=0.000). The incidence of stroke increased with age (chi(2)=410.130, P=0.000). The annual mortality of stroke was 149.67/100 000 and the case fatality rate was 15.14%. Compared with the elderly, the prevalence of cerebral hemorrhage and cerebral infarction were higher in young people. CONCLUSION: The prevalence, incidence, mortality and recurrence rate of cerebrovascular disease were high in the population in Inner Mongolia, ischemic stroke was the major form of cerebrovascular disease. PMID- 26814856 TI - [Demographic characteristics HIV positive cases aged no less than 15 years old and related factors in communicable disease prevention demonstration area in Guangxi Zhuang autonomous region]. AB - OBJECTIVE: To understand the demographic characteristics of the HIV positive cases detected in the screening project in communicable disease prevention demonstration area in Guangxi Zhuang autonomous region and analyses the related factors of HIV infection. METHODS: HIV antibody detection was conducted for local people aged no less than 15 years old in 3 demonstration counties, and the demographic information of the subjects were collected. The factors influencing HIV infection were analyzed with software PASW Statistics 18.0. RESULTS: A total of 770 454 local people aged over 15 years were screened, the HIV infection rate was 1.580/00 among them. The positive cases were mainly married males aged>=30 years and with the educational level of primary school and junior middle school. Thus male, age over 30 years and educational level of primary school and junior middle school. were the common risk factors for HIV infection, whereas being married was a protective factor for HIV infection in 3 demonstration counties, but Han ethnic group and divorced/widowed were risk factors for HIV infection in the demonstration county A, non-farmer, divorced/widowed and educational level of senior middle school were the risk factors for HIV infection in demonstration county B and Han ethnic group and farmer were risk factors HIV infection in demonstration county C. CONCLUSION: It suggested to conduct targeted HIV infection screening according to the survey results to find out the HIV cases in general population. PMID- 26814857 TI - [Survey of prevalence of HIV infection, syphilis and HCV infection and related risk behaviors among club drug users in Zhejiang, 2011]. AB - OBJECTIVE: To understand the prevalence of HIV infection, syphilis and hepatitis C infection and related risk behaviors among club drug users in Zhejiang province. METHODS: The drug users were interviewed with questionnaires in 2011 to collect the information about their demographic characteristics, sexual behaviors, drug use behaviors and the utilization of intervention services. Blood samples were collected from them to detect HIV, syphilis and HCV antibodies. RESULTS: A total of 3 253 drug users were surveyed, in which 1 298 were club drug users, accounted for 39.9%. The proportion of club drug users was high in northern and central Zhejiang, in females, in age group<=25 years, in local residents and in those having commercial sexual behaviors during previous 12 months. Of the 1 298 club drug users, 91.2% were methamphetamine users, 0.1% were infected with HIV (95% CI: 0.0%-0.2%), 8.1% suffered from syphilis (95% CI: 6.6% 9.6%), 17.3% were infected with HCV (95% CI: 15.2%-19.4%). Among the interviewed club drug users, 12.7% were aware of AIDS, 9.2% had injecting drug use histories, 29.6% reported having commercial sex during the previous 12 months, only 33.4% received free condom and counsel, 14.0% received HIV test. Multivariate logistic regression analysis indicated that living in central and southern Zhejiang was associated with syphilis prevalence, HCV infection and injecting drug use behavior, being female was associated with syphilis prevalence. Injecting drug use and commercial sex during the previous 12 months were associated with HCV infection, and injecting drug use and commercial sex during the previous 12 months were associated with each other. Among the 1 285 club drug users, males, local residents in Zhejiang and those who never received free condom or counsel were more likely to have commercial sex. CONCLUSION: The prevalence of syphilis and HCV infection are high and unprotected sexual behaviors are common among the club drug users in Zhejiang, but less intervention services were received by them, suggesting that more attention should be paid to the prevention and control of HIV, HCV infections and syphilis in club drug users by taking effective intervention measures and increasing intervention coverage. PMID- 26814859 TI - [A cross-sectional study of infertility prevalence and influencing factors in Uygur and Kazak women, Xinjiang Uygur autonomous region]. AB - OBJECTIVE: To investigate the prevalence of infertility and related factors in Uygur and Kazak women in Xinjiang Uygur autonomous region (Xinjiang). METHODS: Questionnaire survey and pelvic examination were conducted among 535 Uygur women and 322 Kazak women at reproductive age who were selected through stratified cluster random sampling in Sansan and Fuhai counties in Xinjiang. The data were analyzed with software SPSS 17.0. RESULTS: The prevalence of infertility among the Uygur and Kazak women were 26.5% and 21.7% respectively, the difference was not statistically significant (P>0.05). The prevalence of primary infertility among the Uygur and Kazak women were 14.7%, and 8.7%, respectively, the difference was statistically significant (P<0.05). The prevalence of secondary infertility among the Uygur and Kazak women were 11.8% and 13.0%, respectively, the difference was not statistically significant (P>0.05). The prevalence of infertility in the Uygur women was correlated with household income, pelvic inflammation, endometriosis and BMI, while the prevalence of infertility in the Kazak women was correlated with age of marriage, endometriosis and the history of ectopic pregnancy. CONCLUSION: The prevalence of infertility was high among the Uygur and Kazak women at reproductive age in Xinjiang. The influencing factors varied with ethnic group. It is necessary to conduct targeted health education and provide early diagnosis and effective treatment. PMID- 26814858 TI - [Intervention caused changes in high risk sex behaviors among female sex workers from Vietnam in Yunnan, 2009-2013]. AB - > OBJECTIVE: To understand the prevalence of high risk sex behaviors and HIV infection status among the female sex workers (FSWs) from Vietnam in Yunnan province during a 5 year intervention project and provide evidence for the improvement of the behavior intervention among this population. METHODS: The survey was conducted annually among Vietnamese FSWs sampled in a county near China-Vietnam border to collect the information about their demographic characteristics, high risk sex behaviors and HIV test results through questionnaire and in-depth interview by bilingual outreach team. The behavior intervention included peer advise, training, lectures, interactive games, free condom distribution. The database was set up with Excel 2003 and the results were analyzed with SPSS 16.0. RESULTS: The condom use rates among the Vietnamese FSWs at commercial sex in last month were 1.5%, 36.0%, 67.7%, 86.5% and 90.3% (P<0.05) respectively; and the condom use rates at the latest sex were 89.5%,44.8%, 86.6%,92.5% and 99.0% respectively (P<0.05) . The HIV antibody positive rates were 7.5%, 3.6%, 5.9%, 4.0% and 3.1% respectively (P>0.05). CONCLUSION: The condom use rate of Vietnamese FSWs at commercial sex increased by more than 90% after the 5 year intervention project. However, the HIV-infection rate was still high. It is necessary to promote condom use among FSWs from Vietnam and their regular sex partners and strengthen the health education among clients. PMID- 26814860 TI - [Association between mothers' body mass index before pregnancy or weight gain during pregnancy and autism in children]. AB - OBJECTIVE: To explore the relationship between mothers' body mass index (BMI) before pregnancy or weight gain during pregnancy and autism in children. METHODS: From 2013 to 2014, the 181 children with autism and 181 healthy children matched by sex and age from same area were included in this study. According to mothers' BMI before pregnancy, the selected cases were divided into 3 groups: low, normal and high group. Then 3 groups were divided into 3 subgroups based on mother' s weight gain during pregnancy: low, normal and high group, according to the recommendations of Institute of Medicine. Logistic regression analysis and chi(2) test were conducted with SPSS 18.0 software to analysis the relationship between mothers' BMI before pregnancy or weight gain during pregnancy and autism in children. RESULTS: The age and sex distributions of case group and control group were consistent (chi(2)=0.434, P>0.05). The mothers' BMI before pregnancy of case group was higher than that of control group (chi(2)=9.580, P<0.05) ,which was (21.28+/-3.80) kg/m(2) for case group and (19.87+/-2.83) kg/m(2) for control group. The proportion of cases in high BMI group (10.5%) was much higher than that in control group (2.8%) . The risk of children with autism in high BMI group was 3.7 times higher than that in normal BMI group (OR=3.71, 95% CI: 1.34-10.24). In normal BMI group, the proportion of mothers who had excessive weight gain during pregnancy was higher in case group (44.1%) than in control group (33.9%). In high BMI group, the proportion of mothers who had excessive weight gain was higher in case group (52.6%) than in control group (20.0%) . In normal BMI group (chi(2) =8.690, P<0.05) and high BMI group (chi(2)=4.775, P<0.05), the weight gain during pregnancy was associated with autism in children. Logistic regression analysis showed that mothers' BMI before pregnancy (unadjusted OR=1.89, 95% CI: 1.26-2.85, adjusted OR=1.52, 95% CI: 1.19-2.27) and weight gain during pregnancy were the risk factors for autism in children (unadjusted OR=1.63, 95% CI: 1.08 1.25, adjusted OR=1.64, 95% CI: 1.21-2.21). CONCLUSION: Overweight or obesity before pregnancy and excessive weight gain during pregnancy were associated with autism in children, suggesting that women who plan to be pregnant should pay attention to body weight control. PMID- 26814861 TI - [Association between adverse experiences in childhood and risk of chronic diseases in adulthood]. AB - OBJECTIVE: To analyze the prevalence and characteristics of childhood adverse experiences among adults aged 18-59 years and understand the association between childhood adverse experiences and risk of chronic diseases in adulthood. METHODS: A cross-sectional study was conducted with a questionnaire among adults aged 18 59 years selected through cluster random sampling from 3 communities in Macheng, Hubei province. Uinivariate and multivariate logistic regression analyses were conducted to evaluate the association between adverse experiences in childhood and the risk of chronic diseases in adulthood. RESULTS: A total of 1 767 adults aged 18-59 years were surveyed and 1 501 valid questionnaires were returned. The average age was (36.32+/- 10.20) years for males and (35.72+/-9.08) years for females. The prevalence rate of childhood adverse experiences was 66.22%. The risk of chronic disease in adults increased with the increase of the score indicating childhood adverse experiences (Z=-5.902 1, P<0.000 1). Multivariate logistic regression analysis showed that being physically abused (OR=1.93, 95% CI: 1.41-2.64), substance abuse in family (OR=2.82, 95% CI: 1.16-6.80), being bullied (OR=2.59, 95% CI: 1.39-4.80) and parents separation/divorce (OR=1.51, 95% CI: 1.09-2.09) were significantly associated with risk of chronic diseases in adulthood. CONCLUSION: The prevalence of adverse childhood experiences was high in adults aged 18-59 years, which was significantly associated with the risk of chronic diseases in adulthood. Early prevention of chronic diseases should be conducted in childhood. PMID- 26814862 TI - [Prevalence and metabolic risk factors of nonalcoholic fatty liver disease in a middle-aged and elderly population in Guangzhou]. AB - OBJECTIVE: To investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) and understand the relationship between NAFLD and metabolic risk factors in middle-aged and elderly adults. METHODS: This cross-sectional study recruited 2 935 subjects in Guangzhou, Guangdong province. Face-to-face interviews and laboratory analyses were conducted to collect general information and other covariates. Analysis of covariance and logistic regression analysis were performed to investigate the relationship between metabolic factors and the prevalence of NAFLD. NAFLD was diagnosed based on standard criteria recommend by the Fatty Liver Disease and Alcoholic Liver Disease Branch of Chinese Hepatology Society, and the degree of steatosis was assessed (mild, moderate or severe). RESULTS: Compared with normal subjects, those with NAFLD had higher levels of WC, BMI, FPG, TG, SBP, DBP and greater prevalence of metabolic syndrome, but lower levels of physical activity and HDL-C. After adjusted for covariates, the OR for each standard deviation change was 2.70 (95% CI: 2.45-2.98) for WC, 1.47 (95% CI: 1.35-1.59) for SBP, 1.48 (95% CI: 1.37-1.60) for DBP, 1.88 (95% CI: 1.66-2.12) for TG, 1.25 (95% CI: 1.15-1.36) for FPG and 0.51 (95% CI: 0.47-0.56) for HDL-C (all P<0.001). Higher levels of WC, BMI, TG, SBP, DBP and FPG were significantly related with the increase in degree of NAFLD (P-trend<0.001). CONCLUSION: There is a relatively high prevalence of NAFLD in middle-aged and elderly adults in China. NAFLD is closely related with the different forms of metabolic syndrome, and WC is the leading risk factor for NAFLD. PMID- 26814863 TI - [Study on factors associated with family burden of Alzheimer' s disease]. AB - OBJECTIVE: To understand the family burden of Alzheimer' s disease (AD) and associated factors. METHODS: The subjects were 168 caregivers of patients with AD selected from two class 3A hospitals and three communities in Taiyuan through cluster sampling. The data were collected by using the Caregiver Burden Inventory (CBI) and the Family Burden Scale (FBS) of diseases. Path analysis was applied to identify the factors associated with the total score of CBI. T-test and One-way analysis of variance were applied to identify the factors associated with the total score of FBS. Multiple linear regression analysis was applied to identify the factors associated with family burden of AD. RESULTS: The total score of the caregivers' burden was 52.41+/-17.07. AD patients' cognitive function had direct (standardized beta =-0.280, P<0.001) and indirect effect on CBI; while daily performance of AD patients had indirect effect on CBI. The total score of family burden was 16.23+/- 9.00. Univariate analysis showed that the sex, age, education level, cognitive function, daily performance, mental status, depression and dementia rating of AD patients might affect the total score of FBS (P<0.05) . Multivariate analysis showed that the factors which affected the total score of FBS included the sex (standardized beta=0.280, P<0.01) , cognitive function (standardized beta=-0.158, P=0.033) and daily performance of AD patients (standardized beta=-0.155, P=0.039). CONCLUSION: The caregiver and family burden of AD was mainly associated with the cognitive function and daily performance of AD patients. It is necessary to take targeted measures to reduce the caregiver and family burden of AD. PMID- 26814864 TI - [Evaluation of performance of national injury surveillance in China, 2006-2012]. AB - OBJECTIVE: To evaluate the performance of national injury surveillance in China and provide evidence for the utilization and interpretation of surveillance data and the improvement of injury surveillance. METHODS: According to the national injury surveillance protocol, a retrospective analysis was conducted on the quality of injury surveillance carried out by the centers for disease control and prevention (CDCs) at all levels in China from 2006 to 2012. And related human resource and budget data in 2012 were collected for analysis. RESULTS: From 2006 to 2012, the injury cases reported to national injury surveillance system increased by 1 time in China. The underreporting rate of injury cases and mis filling rate of reporting cards decreased in 31 surveillance points (72.1%) and 23 surveillance points (53.5%) respectively. In 2012, the underreporting rates were less than 10% in 33 surveillance points (76.7%) , and the mis-filling rates were less than 10% in 39 surveillance points (90.7%) . Only 19 provincial CDCs (44.2%) and 32 county/district CDCs had full time staff engaged in injury surveillance. Three surveillance points (7.0%) never published their injury surveillance data, while 13 surveillance points shared injury surveillance data with other departments. CONCLUSION: The quality of injury surveillance was greatly improved in China during 2006-2012, but more efforts are still needed for the further improvement of national injury surveillance, including the increase of human resources and fund investments and more use of surveillance data. PMID- 26814865 TI - [Sex specific mortality in HIV/AIDS patients receiving antiretroviral therapy and risk factors in Xinjiang Uygur autonomous region]. AB - OBJECTIVE: To analyze the sex specific mortality in HIV/AIDS patients receiving highly active antiretroviral therapy (HAART) and risk factors in Xinjiang Uyghur autonomous region (Xinjiang), and provide evidence for the evaluation of the effect of HAART. METHODS: A retrospective analysis was conducted on the mortality and survival of 8 061 male cases and 6 001 female cases of HIV infection, who received HAART during July 2004-June 2013 in Xinjiang. The information of the cases were downloaded from national antiretroviral therapy reporting sub-system in national HIV/AIDS reporting system. Cox proportional hazard model was used to identify the risk factors of deaths. RESULTS: The male cases were older and had lower CD4 value at baseline compared with the female cases. The major transmission route was injecting drug use in males, but sexual contact in females. The overall mortality of the male cases was higher than that of the females, which was 10.87/100 person-years during the first three month after receiving HAART, and 7.00/100 person-years two years later in males, but 4.77/100 person-years during the first three month and 3.00/100 person-years two years later in females. The results from Cox analysis showed that the risk factors were the CD4 value at baseline and transmission route. Compared with the cases who had lower CD4 value (CD4<200 cells/ul) at baseline, the HR for the cases who had higher CD4 value (CD4>=350 cells/ul) was 4.08 (95% CI: 2.96-5.62) in males and 5.11 (95% CI: 3.16-8.35) in females. Compared with sexual transmission, the HR for IDUs was 1.99 (95% CI: 1.66-2.40) in males and 1.77 (95% CI: 1.24-2.52) in females. The results of cumulative survival analysis showed that in conventional treatment group (CD4<350 cells/ul) , the five year survival rates were 81% and 87% for the males and females infected through sexual contact and 66% and 75% for the males and females infected through injecting drug use, and in early treatment group (CD4>=350 cells/ul) , the five year survival rates were 97% and 98% for the males and females infected through sexual contact and 86% and 97% for the males and females infected through injecting drug use. CONCLUSION: In Xinjiang, the higher mortality in male HIV infection cases receiving HAART was related with lower CD4 value at baseline and higher infection rate through injecting drug use. Besides the weak intention for treatment and poor compliancy would be the deeper risk factors. PMID- 26814866 TI - [Analysis on death causes of residents in Anhui province, 2013]. AB - OBJECTIVE: To analyze the demographic characteristics and the death causes of the residents in Anhui province, and provide evidence for the disease prevention and control. METHODS: Using descriptive epidemiological analysis, the demographic characteristics and death data of the national disease surveillance points (DSPs) in Anhui province in 2013 were analyed by areas. RESULTS: The aging of the population was observed in all the areas in Anhui, which was most obvious in Jianghuai, followed by Wannan and Huaibei. The overall mortality was 627.10/100 000. The mortalities of diseases varied with sex, area and age. Among the 3 areas, the overall mortality, chronic disease mortality and injury mortality were highest in Huaibei and lowest in Wannan. The area specific difference in mortality of infectious diseases was small. Regardless of areas or the types of diseases, the mortality was higher in males than in females. Deaths caused by diseases with unknown origins were common in residents aged >65 years. The mortality of chronic diseases was higher in residents aged >45 years, especially in those aged 65-84 years. The mortality of injuries was higher in age groups >15 years and >45 years. The mortality of infectious diseases peaked at both young age group and old age group. The top five death causes were cerebrovascular diseases, malignant tumors, heart diseases, respiratory diseases and injuries. Regardless of sex or area, the major death causes were similar, but the ranks were slightly different. The major death causes varied in different age groups, but they were similar in same age group in different areas. The major death causes were diseases originated in perinatal period, and congenital malformations, deformations and chromosomal abnormalities in children aged <1 year. The major death causes in children aged 1-14 years were injuries, diseases originated in perinatal period, congenital malformations, deformations and chromosomal abnormalities. Injuries and malignant tumors were the first and second death causes in residents aged 15-44 years. Malignant tumors, injuries, cerebrovascular diseases and heart diseases were the major death causes in residents aged 45-64 years. The major death causes were cerebrovascular diseases, malignant tumors, heart diseases and respiratory diseases in residents aged 65-84 years and heart diseases, cerebrovascular diseases, respiratory diseases and malign tumors in residents aged>=85 years. CONCLUSION: The major death causes in residents in Anhui province were cerebrovascular diseases, malignant tumors and injuries. Close attention should be paid to the prevention and control of cerebrovascular diseases, malignant tumors and heart diseases in age group>=45 years. It is necessary to strengthen the prevention and control of injuries in age group 15-44 years. Huaibei is a key area of disease prevention and control in Anhui, especially chronic disease and injury preventions. PMID- 26814867 TI - [Prediction and analysis of epitopes of hemagglutinin of measles virus]. AB - OBJECTIVE: To discuss the antigenic change caused by the mutation of amino acid on the epitopes of the hemagglutinin of measles virus. METHODS: The B cell linear epitopes in the hemagglutinin were predicted with bioinformatics software. Peptide pairs, which located on the same region but originated from measles vaccine and wild-type virus respectively, were designed and synthesized. After detecting the immunogenicity of peptides with indirect ELISA assay, sera against each peptide was prepared. Antigenic specificity between the two peptides within each peptide pair were tested by using cross ELISA assay, and then antigen ratios were calculated. RESULTS: All the synthesized peptides could bind with immune sera against measles virus, of which the peptide pair CW23/CW22 designed on the epitope region (273-282 aa) possessed the highest binding ability, while the peptide pair CW150/CW151 designed on the non-epitope region (418-427 aa) showed the lowest binding ability. The difference in antigenic specificity between the two peptides from different sources was significant. The antigenic ratio was up to 16 between CW23 (vaccine-originated) and CW22 (wild-type originated) , and 2.877+/-0.583 between CW123 (vaccine-originated) and CW124 (wild-type originated) (236-246 aa) . On the non-epitope regions, the antigenic ratios was only 1.631+/ 0.481 between peptide pair CW125 and CW126 (356-364 aa) , but reached to 10.367+/ 1.617 between CW150 and CW151. CONCLUSION: Although there were several conservative epitopes, specific amino acid mutation on the predicted epitope or non-epitope regions might cause the antigenic change of wild-type measles virus. PMID- 26814868 TI - [Analysis on gene sequence of HIV isolated from men who have sex with men in Beijing]. AB - OBJECTIVE: To analyze genetic characteristics of HIV isolated from men who have sex with men (MSM) in Beijing and predict the epidemic trend in this population. METHODS: All of the HIV gene sequences in our laboratory obtained from MSM in Beijing were used, which were aligned with all of the HIV gene sequences from MSM and other populations in China downloaded from Los Alamos HIV Database. Phylogenetic trees were constructed by using software PhyML 3.0, based on which the relationships of prevalent HIV strains between Beijing MSM and other populations in China were further explored. The evolution rate, the time of most recent common ancestor (tMRCA) , the epidemic parameters, the reproductive number (R0) were calculated by using software BEAST to predict HIV evolution and epidemic characteristics. RESULTS: Multiple HIV subtypes, including subtype B, CRF01_AE and CRF07_BC, were found to be prevalent among MSM in Beijing. In ML tree constructed based on strains from the whole country, three clusters including B-1, CRF01_AE-1, and CRF01_AE-2 were found among the MSM in Beijing (accounting for 40%) . At least three independent introduction of B1 cluster strains into Beijing MSM were found, which were at March 1991 (July 1984-February 1997) , January 1994 (January 1989-January 1998) , April 1991 (August 1984 January 1996) . For CRF01_AE strains, two clusters including CRF01_AE-1 and CRF01_AE-2 were introduced into the population at December 2000 (March 1998 January 2003) and December 2001 (January 2000-July 2003) respectively. The population epidemiology of HIV in Beijing MSM was reconstructed based on sequences. The CRF01_AE-1 cluster spread more quickly than the other two clusters, and the evolution rate was higher. CONCLUSION: Multiple HIV subtypes were found prevalent among MSM in Beijing. Although subtype B strain was introduced into Beijing MSM earlier than CRF01_AE strain, CRF01_AE strain increased more quickly than subtype B strain. More research and control of the CRF01_AE prevalence will be helpful for prevention and control of HIV epidemic in MSM in Beijing. PMID- 26814869 TI - [Analysis on genotypes of hepatitis C virus among intravenous drug users in Kunming, Yunnan]. AB - OBJECTIVE: To investigate the distribution of hepatitis C virus (HCV) subtypes among intravenous drug users (IDUs) in Kunming, Yunnan province, in 2014. METHODS: A total of 276 plasma samples were collected from IDUs in Kunming during April 2014 -July 2014, in which 199 plasma samples were tested to be HCV antibody positive. For the HCV antibody positive samples, HCV E1E2 genes and NS5B genes were amplified by using nested-polymerase chain reaction (PCR). After sequencing, the HCV subtypes were determined through phylogenetic analysis. RESULTS: Based on the phylogenetic trees of E1E2 gene and NS5B gene fragments, a total of 125 samples were genotyped. 3b was the predominant subtype (48.8%,61/125), followed by 3a (30.4%, 38/125), 6n (14.4%, 18/125), 6a (3.2%, 4/125) and 1b (3.2%, 4/125). The distributions of HCV subtypes by sex, marital status, ethnic group and HIV-1 infection status showed no statistical differences. However, the distribution of HCV subtypes by age showed statistical difference, the diversity of HCV subtypes was found in age group <45 years. The genetic distances of 3a, 3b and 6a on E1E2 and NS5B were larger than those of 1b and 6n. For genotype 3, the genetic distances of 3b on E1E2 and NS5B were larger than those of 3a. CONCLUSION: Five HCV subtypes were found among IDUs in Kunming, HCV subtypes 3b and 3a were predominant, which have circulated in this population for long time. PMID- 26814870 TI - [Association between tumor necrosis factor superfamily member 4 gene polymorphism and risk of asymptomatic carotid vulnerable plaque in a Chinese population]. AB - OBJECTIVE: Vulnerable plaque of carotid artery is one of the risk factors of atherosclerotic cerebral infarction. Detection and treatment of vulnerable atherosclerotic plaque of carotid artery before symptoms of cerebral infarction is an effective way to prevent atherosclerotic cerebral infarction. Tumor necrosis factor superfamily member 4 (TNFSF4) plays a key role in the process of atherosclerosis, a common risk factor for both myocardial and cerebral infarctions. Studies have indicated that the single nucleotide polymorphism (SNP) rs3850641 in TNFSF4 is associated with higher risk of myocardial infarction and SNP rs3861950 in TNFSF4 is associated with higher risk of atherosclerosis cerebral infarction (ACI) ,but little is known about the association between TNFSF4 variations and vulnerable plaque of carotid artery. METHODS: A case control study involving 510 patients with asymptomatic vulnerable plaque of carotid artery and 485 age and sex matched healthy subjects without vulnerable plaque of carotid artery was conducted in Hunan province. Asymptomatic vulnerable plaque of carotid artery means vulnerable plaque of carotid artery without cerebral infarction. Two SNPs of TNFSF4, rs3850641 and rs3861950, were genotyped by the TaqMan SNP genotyping method, and verified partly by Genomic DNA Sequencing. RESULTS: The results revealed a significant allelic association between rs3861950 and asymptomatic vulnerable plaque of carotid artery in case group (chi(2)=9.13, P=0.003; OR=1.41, 95%CI: 1.12-1.76). Compared with control subjects, the difference in genotype was significant in case group (chi(2)=25.28, P<0.000 1). However, there was no significant association between rs3850641 and asymptomatic vulnerable plaque of carotid artery (OR=1.16, 95%CI: 0.92-1.46; chi(2)=1.47, P=0.225). CONCLUSION: TNFSF4 gene polymorphism rs3861950 was associated with the risk of vulnerable plaques of carotid artery in a Chinese population, which might be middle phenotype indicating higher risk of cerebral infarction. PMID- 26814871 TI - [A cross-sectional survey of performance of chemotherapy for echinococcosis in Xinjiang Uygur autonomous region]. AB - OBJECTIVE: To understand the performance of echinococcosis chemotherapy in echinococcosis endemic areas in Xinjiang Uygur autonomous region (Xinjiang). METHODS: A questionnaire survey was conducted in the First Affiliated Hospital of Xinjiang Medical University, Hoboksar Mongolia autonomous county, Ermin and Yumin counties from April to June in 2013. RESULTS: A total of 329 echinococcosis patients were surveyed, and chemotherapy was provided according to WHO echinococcosis treatment recommendation, the standard treatment rate was and non standardized medication was 49.2% (162/329) and 50.8% (167/329), respectively. CONCLUSION: It is necessary to standardize the chemotherapy of echinococcosis in some echinococcosis endemic areas in Xinjiang. The comprehensive prevention and treatment include standardized diagnosis, surgical treatment and chemotherapy as well as follow up for individualized treatment. PMID- 26814872 TI - [Meta-analysis of association between organophosphorus pesticides and aplastic anemia]. AB - OBJECTIVE: To evaluate the association between organophosphorus pesticides and aplastic anemia, and provide scientific evidence for the primary prevention of aplastic anemia. METHODS: The published papers of case control studies on the association between organophosphorus pesticides and aplastic anemia from January 1990 to August 2014 were collected from Chinese BioMedical Literature Base (CBM), Chinese National Knowledge Infrastructure (CNKI), PubMed and EMBASE. The papers which met the inclusion criteria were evaluated. The pooled odds ratios (OR) and 95% confidence interval (CI) of organophosphorus pesticides were calculated with software Review Manager 5.0. Subgroup analysis were conducted for different population and different usage of organophosphorus pesticides. RESULTS: A total of 9 papers were selected, involving 5 833 subjects (1 404 cases and 4 429 controls). The results showed that organophosphorus pesticides could increase the risk of aplastic anemia (OR=1.97, 95% CI: 1.60-2.44) . Subgroup analysis showed that Asian (OR=2.01, 95% CI: 1.52-2.66) had higher risk of aplastic anemia than American or European (OR=1.93, 95% CI: 1.39-2.67) . Using pure organophosphorus pesticides (OR=2.15, 95% CI: 1.60-2.88) was more prone to cause aplastic anemia than using the mixture of organophosphorus pesticides (OR=1.82, 95% CI: 1.34 2.47). CONCLUSION: The analysis indicated that organophosphorus pesticides might be a risk factor for aplastic anemia. Reducing organophosphorus pesticides exposure in daily life and industrial or agricultural production could prevent the incidence of aplastic anemia. PMID- 26814873 TI - [Association between retinol-binding protein 4 and coronary artery disease in Chinese: a Meta-analysis]. AB - OBJECTIVE: To evaluate the association between retinol-binding protein 4 (RBP4) and coronary artery disease (CAD) in Chinese. METHODS: A document retrieval was conducted by using retrieval systems, such as PubMed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) ,CBM, VIP and WanFang Database, to collect the published papers of case-control studies on association between RBP4 and CAD in Chinese up to February, 2015. Data collection and quality assessment were completed by two authors respectively. All the analyses were conducted with software RevMan 5.2. RESULTS: A total of 10 qualified studies were included in our meta-analysis. The pooled analysis showed that RBP4 might be associated with CAD in Chinese [WMD=7.17 (95% CI: 3.56-10.78) ug/ml, P<0.05]. Clinical subtype specific subgroup analysis showed RBP4 might be also associated with both stable angina pectoris [WMD=4.81 (95% CI: 1.25-8.37) ug/ml, P<0.05 ] and acute myocardial infarction [WMD=13.96 (95% CI: 6.12-21.80) ug/ml, P<0.05]. Age specific subgroup analysis showed the significant association between RBP4 and CAD was only found in patients aged<=65 years [WMD=7.26(95% CI:2.73-11.79) ug/ml, P<0.05]. Sensitivity and publication bias analyses indicated that our results were stable and reliable. CONCLUSION: The meta-analysis suggests that RBP4 might be associated with CAD in Chinese. PMID- 26814874 TI - [Interrupted time-series analysis and its application in public health]. PMID- 26814875 TI - [Quasi-experiment study]. PMID- 26814876 TI - [Research progress in job burnout among HIV-related health care workers]. PMID- 26814877 TI - [The major progress on the Ebola virus disease study and international Ebola virus testing in Sierra Leone]. PMID- 26814878 TI - [The role of international cooperation in the prevention and control of ebola virus disease epidemic in Sierra Leone]. PMID- 26814879 TI - [Ebola virus disease emergency response organization and command system in Sierra Leone]. PMID- 26814880 TI - [Analysis of mechanism for international joint prevention and control of Ebola virus disease in Sierra Leone]. PMID- 26814881 TI - [Comparison of international Ebola virus testing laboratories in Ebola virus disease outbreak in Sierra Leone]. PMID- 26814882 TI - [The application and Expectation of mobile BSL-3 laboratory during outbreak of Ebola virus disease in Serra Leone]. PMID- 26814883 TI - Genitourinary trauma in geriatric patients. AB - PURPOSE OF REVIEW: The geriatric population is the fastest growing segment of the population, and geriatric trauma patients are increasingly common. Caring for this population has unique challenges. The goal of the review is to identify factors that may help in the care of geriatric patients suffering from genitourinary trauma. RECENT FINDINGS: Multiple factors lead to inferior outcomes in patients with geriatric trauma including failure to rescue, treatment in lower volume trauma centers, and undertriage of geriatric patients. Improvement in geriatric trauma outcomes occurs with the use of dedicated geriatric consult teams. The surgical management of genitourinary injuries in the geriatric population remains unchanged. SUMMARY: Interventions for geriatric patients differ from younger populations. Direct changes in overall management of the geriatric population lead to improved outcomes. The treatment of geriatric trauma patients with genitourinary injuries is similar to a younger cohort. The lack of recent studies in clinical outcomes in this population has been identified as a gap in knowledge that will require future research to answer. PMID- 26814884 TI - Translational approaches to the treatment of benign urologic conditions in elderly women. AB - PURPOSE OF REVIEW: Stress urinary incontinence, overactive bladder, interstitial cystitis/painful bladder syndrome, and underactive bladder are highly prevalent among elderly women, and have significant impact on quality of life; however, existing treatments are limited and are not always successful for all patients. Researchers are investigating a multitude of new therapies to treat these conditions. This review will summarize the recent literature on investigative therapies for these conditions. RECENT FINDINGS: Multiple new treatments are being developed for lower urinary tract dysfunction. Some of these treatments, including balloon therapy and muscle-derived stem cells for stress urinary incontinence, could provide alternatives to existing therapies. Others require further research before being used in patients, such as pudendal nerve stimulation for overactive bladder and intravesical liposomes for drug delivery in interstitial cystitis/painful bladder syndrome. SUMMARY: Multiple new therapies are being investigated that could provide clinicians with additional tools to treat lower urinary tract disorders in millions of elderly women. PMID- 26814885 TI - Men's health and quality of life. PMID- 26814886 TI - Exhaled and non-exhaled non-invasive markers for assessment of respiratory inflammation in patients with stable COPD and healthy smokers. AB - We aimed at comparing exhaled and non-exhaled non-invasive markers of respiratory inflammation in patients with chronic obstructive pulmonary disease (COPD) and healthy subjects and define their relationships with smoking habit. Forty-eight patients with stable COPD who were ex-smokers, 17 patients with stable COPD who were current smokers, 12 healthy current smokers and 12 healthy ex-smokers were included in a cross-sectional, observational study. Inflammatory outcomes, including prostaglandin (PG) E2 and 15-F2t-isoprostane (15-F2t-IsoP) concentrations in exhaled breath condensate (EBC) and sputum supernatants, fraction of exhaled nitric oxide (FENO) and sputum cell counts, and functional (spirometry) outcomes were measured. Sputum PGE2 was elevated in both groups of smokers compared with ex-smoker counterpart (COPD: P < 0.02; healthy subjects: P < 0.03), whereas EBC PGE2 was elevated in current (P = 0.0065) and ex smokers with COPD (P = 0.0029) versus healthy ex-smokers. EBC 15-F2t-IsoP, a marker of oxidative stress, was increased in current and ex-smokers with COPD (P < 0.0001 for both) compared with healthy ex-smokers, whereas urinary 15-F2t-IsoP was elevated in both smoker groups (COPD: P < 0.01; healthy subjects: P < 0.02) versus healthy ex-smokers. FENO was elevated in ex-smokers with COPD versus smoker groups (P = 0.0001 for both). These data suggest that the biological meaning of these inflammatory markers depends on type of marker and biological matrix in which is measured. An approach combining different types of outcomes can be used for assessing respiratory inflammation in patients with COPD. Large studies are required to establish the clinical utility of this strategy. PMID- 26814887 TI - The Many Facets of Lipooligosaccharide as a Virulence Factor for Histophilus somni. AB - The lipooligosaccharide (LOS) of Histophilus somni is a multifaceted molecule that provides critical protection to the bacterium against host defenses, may act as an adhesin, and like similar molecules of gram-negative bacteria, is an endotoxin that signals through toll-like receptor 4 and NF-kappaB to cause inflammation. The lipid A component is responsible for the endotoxic and apoptotic activity of the LOS. The H. somni LOS lacks O-side chains typically characteristic of gram-negative bacteria that have lipopolysaccharide, but has a complex, microheterogeneous outer core. The LOS of disease isolates is capable of undergoing structural and antigenic phase variation of its outer core due to slip strand mispairing of glycosyltransferase genes that contain repetitive sequences of DNA base pairs. Such variation enables the bacteria to evade bactericidal antibodies made to oligosaccharide antigens. In addition, the LOS can be decorated with phase-variable phosphorylcholine (ChoP), which binds to platelet activating factor receptor on host cells, thereby aiding in colonization of the upper respiratory tract. However, ChoP is likely not expressed when the bacteria are in systemic sites because ChoP also binds to C-reactive protein, resulting in activation of host complement and promoting bactericidal activity. The structure of some LOS outer core chains is identical to oligosaccharides on host glycosphingolipids of red blood cells, other cells, and merconium (lacto-N neotetraose, lacto-N-biose, N-acetyllactosamine, etc.). Furthermore, terminal galactose residues on LOS and elsewhere are decorated with sialic acid, which blocks antibody binding, activation of complement, phagocytosis, and intracellular killing. Therefore, antigenic mimicry of host antigens is an important defense mechanism provided by the oligosaccharide component of the LOS to avoid innate and adaptive host defense mechanisms. However, some strains of H. somni isolated from the bovine genital tract, particularly the normal bovine prepuce, are incapable of LOS phase variation, sialylation of the LOS, and expression of ChoP. At least 1 such strain has been shown to be avirulent, underscoring the importance of the LOS as a virulence factor, although this strain is deficient in other factors as well. The structure and arrangement of the inner core glycoses (heptose and 3-deoxy-D-manno-2-octulosnic acid) is remarkably similar to the inner core oligosaccharide on some strains of Neisseria spp., and mutants that contain a truncated LOS oligosaccharide are considerably more serum-sensitive than the parent strain. Therefore, the LOS is a critical component that enables H. somni to resist host defenses and cause disease. PMID- 26814888 TI - The Amyloid Precursor Protein of Alzheimer's Disease Clusters at the Organelle/Microtubule Interface on Organelles that Bind Microtubules in an ATP Dependent Manner. AB - The amyloid precursor protein (APP) is a causal agent in the pathogenesis of Alzheimer's disease and is a transmembrane protein that associates with membrane limited organelles. APP has been shown to co-purify through immunoprecipitation with a kinesin light chain suggesting that APP may act as a trailer hitch linking kinesin to its intercellular cargo, however this hypothesis has been challenged. Previously, we identified an mRNA transcript that encodes a squid homolog of human APP770. The human and squid isoforms share 60% sequence identity and 76% sequence similarity within the cytoplasmic domain and share 15 of the final 19 amino acids at the C-terminus establishing this highly conserved domain as a functionally import segment of the APP molecule. Here, we study the distribution of squid APP in extruded axoplasm as well as in a well-characterized reconstituted organelle/microtubule preparation from the squid giant axon in which organelles bind microtubules and move towards the microtubule plus-ends. We find that APP associates with microtubules by confocal microscopy and co-purifies with KI-washed axoplasmic organelles by sucrose density gradient fractionation. By electron microscopy, APP clusters at a single focal point on the surfaces of organelles and localizes to the organelle/microtubule interface. In addition, the association of APP-organelles with microtubules is an ATP dependent process suggesting that the APP-organelles contain a microtubule-based motor protein. Although a direct kinesin/APP association remains controversial, the distribution of APP at the organelle/microtubule interface strongly suggests that APP organelles have an orientation and that APP like the Alzheimer's protein tau has a microtubule-based function. PMID- 26814889 TI - Effect of smoking cessation counseling within a randomised study on early detection of lung cancer in Germany. AB - INTRODUCTION: In the German lung cancer screening trial LUSI, smoking cessation counseling (SCC) was offered to all participants at time of randomization, and smoking habits were asked for within annual questionnaire inquiries. We analyzed the smoking habits of the participants within the first 2 years of follow-up and especially the potential effect of the SCC on these habits. MATERIALS AND METHODS: We used the smoking data of the initial inquiry on which the decision on invitation to the study was based, the socio-economic data of the questionnaire filled-in at time of randomization, the psycho-social data obtained during the SCC, and the annual questionnaire data of the first two annual follow-up screening rounds. RESULTS: Smoking prevalence decreased in the entire cohort significantly by 4 %, whereby the decrease was with 4.5 % statistically not significantly higher in the control arm than in the screening arm with 3.4 %. The decline was much stronger in the subgroup of attendees to stop-smoking counseling and mounted up therein to 10 %. In some participants, an increase of readiness to quit smoking was observed during the counseling hour, but did not show effects on smoking status 2 years later. DISCUSSION: We did not see a tendency to increased smoking among participants of the intervention arm or the entire study. The decline of smoking prevalence among the attendees of the counseling might be due to self-selection. Since the issue of effectiveness of smoking cessation counseling is important, further research with randomization into offering counseling or no intervention should be taken into consideration. PMID- 26814890 TI - Structure-Activity Relationship Study of Rakicidins: Overcoming Chronic Myeloid Leukemia Resistance to Imatinib with 4-Methylester-Rakicidin A. AB - Natural product rakicidin A induces cell death in TKI-resistant chronic myelogenous leukemia (CML) cells. Therefore, 14 rakicidin A analogues were synthesized via a highly efficient combinatorial strategy and were evaluated against CML cell lines. The conjugated diene moiety was found to be crucial for the anti-CML activity of rakicidin A, and the changes in the configuration(s) at C-2, C-3, C-14, C-15, and C-16 resulted in lower levels of anti-CML activity. The most promising compound was 4-methylester rakicidin A (1a). Compared with rakicidin A, 1a exhibited 2.8-fold greater potency against the imatinib-resistant cell line K562/G(+) and approximately 100-fold enhanced potency compared with that of imatinib. Furthermore, compound 1a demonstrated a significantly lower resistance index against Ba/F3 cells expressing BCR-ABL(T315I) than bosutinib, dasatinib, nilotinib, and ponatinib, while 1a exhibited less effect on normal hematopoietic cells. Preliminary results indicated that 1a down-regulated caspase 3 and PARP, which contributes to its K562 cell inhibitory activity. PMID- 26814893 TI - Erratum to: Reliability of classification for post-traumatic ankle osteoarthritis. PMID- 26814892 TI - A Protective Role for Androgen Receptor in Clear Cell Renal Cell Carcinoma Based on Mining TCGA Data. AB - Androgen receptor (AR) is expressed in normal murine and human kidneys of both genders, but its physiologic role is uncertain. Several studies showed loss of AR in renal cell carcinoma (RCC) in conjunction with increasing clinical stage and pathological grade, but others found that higher AR expression correlated with worse outcomes. Limited functional studies with renal cell lines suggested tumor promoting activity of AR. In this study, we queried transcriptomic, proteomic, epigenetic and survival data from The Cancer Genome Atlas (TCGA) to evaluate AR expression and its association with overall survival in three subtypes of RCC (clear cell [ccRCC], papillary [pRCC], and chromophobe [chRCC]). We found that although there was no significant difference in AR mRNA expression in ccRCC of males vs. females, AR protein expression in ccRCC was significantly higher in male compared to female patients. More importantly, higher expression of AR at both transcript and protein levels was associated with improved overall survival in both genders with ccRCC, but did not predict survival of either gender with pRCC or chRCC. Genes whose transcript levels were associated with AR mRNA levels significantly overlapped between ccRCC and pRCC, but not with chRCC, suggesting a similar transcriptional program mediated by AR in ccRCC and pRCC. Ingenuity pathway analysis also identified overlapping pathways and upstream regulators enriched in AR-associated genes in ccRCC and pRCC. Hypermethylation of CpG sites located in the promoter and first exon of AR was associated with loss of AR expression and poor overall survival. Our findings support a tumor suppressor role for AR in both genders that might be exploited to decrease the incidence or progression of ccRCC. PMID- 26814891 TI - Immune Activation in the Female Genital Tract: Expression Profiles of Soluble Proteins in Women at High Risk for HIV Infection. AB - Soluble cervicovaginal biomarkers of inflammation, immune activation and risk of HIV acquisition are needed to reliably assess the safety of new biomedical prevention strategies including vaccines and microbicides. However, a fuller understanding of expression profiles in women at high risk for HIV infection is crucial to the effective use of these potential biomarkers in Phase 3 trial settings. We have measured 45 soluble proteins and peptides in cervicovaginal lavage samples from 100 HIV negative women at high risk for HIV infection. Women were followed over one menstrual cycle to investigate modulation by hormonal contraception, menstrual cycle phase, recent sexual exposure and intravaginal practices. Women using injectable DMPA had increased concentration of several soluble proteins of the innate and adaptive immune system, including IL-1alpha, IL-1beta, IL-2, MIP-1beta, IP-10, IL-8, TGF-beta, HBD4, IgA, IgG1, and IgG2. Women using combined oral contraceptives had a similar signature. There were differences in concentrations among samples from post-ovulation compared to pre ovulation, notably increased immunoglobulins. Increased prostate-specific antigen, indicative of recent sexual exposure, was correlated with increased IL 6, MCP-1, and SLPI, and decreased GM-CSF and HBD3. The identified signature profiles may prove critical in evaluating the potential safety and impact on risk of HIV acquisition of different biomedical intervention strategies. PMID- 26814896 TI - Focus on Disaster Medicine Introduction to the second "Focus-on" Disaster and Military Surgery. PMID- 26814897 TI - Major Incident Hospital: Development of a Permanent Facility for Management of Incident Casualties. AB - INTRODUCTION: Preparation is essential to cope with the challenge of providing optimal care when there is a sudden, unexpected surge of casualties due to a disaster or major incident. By definition, the requirements of such cases exceed the standard care facilities of hospitals in qualitative or quantitative respects and interfere with the care of regular patients. To meet the growing demands to be prepared for disasters, a permanent facility to provide structured, prepared relief in such situations was developed. METHODS: A permanent but reserved Major Incident Hospital (MIH) has been developed through cooperation between a large academic medical institution, a trauma center, a military hospital, and the National Poison Information Centre (NVIC). The infrastructure, organization, support systems, training and systematic working methods of the MIH are designed to create order in a chaotic, unexpected situation and to optimize care and logistics in any possible scenario. Focus points are: patient flow and triage, registration, communication, evaluation and training. Research and the literature are used to identify characteristic pitfalls due to the chaos associated with and the unexpected nature of disasters, and to adapt our organization. RESULTS: At the MIH, the exceptional has become the core business, and preparation for disaster and large-scale emergency care is a daily occupation. An Emergency Response Protocol enables admittance to the normally dormant hospital of up to 100 (in exceptional cases even 300) patients after a start-up time of only 15 min. The Patient Barcode Registration System (PBR) with EAN codes guarantees quick and adequate registration of patient data in order to facilitate good medical coordination and follow-up during a major incident. DISCUSSION: The fact that the hospital is strictly reserved for this type of care guarantees availability and minimizes impact on normal care. When it is not being used during a major incident, there is time to address training and research. Collaboration with the NVIC and infrastructural adjustments enable us to not only care for patients with physical trauma, but also to provide centralized care of patients under quarantine conditions for, say, MRSA, SARS, smallpox, chemical or biological hazards. Triage plays an important role in medical disaster management and is therefore key to organization and infrastructure. Caps facilitate role distribution and recognizibility. The PBR resulted in more accurate registration and real-time availability of patient and group information. Infrastructure and a plan is not enough; training, research and evaluation are necessary to continuously work on disaster preparedness. CONCLUSION: The MIH in Utrecht (Netherlands) is a globally unique facility that can provide immediate emergency care for multiple casualties under exceptional circumstances. Resulting from the cooperation between a large academic medical institution, a trauma center, a military hospital and the NVIC, the MIH offers not only a good and complete infrastructure but also the expertise required to provide large-scale emergency care during disasters and major incidents. PMID- 26814898 TI - The 2001 World Trade Center Disaster: Summary and Evaluation of Experiences. AB - OBJECTIVES: To collect and analyze data from deaths and injuries, and from evaluation of the responses by medical services and by fire, rescue, and police services 1 year after the terror attack on World Trade Center. METHODOLOGY: Epidemiologic data were collected from all involved agencies and analyzed. The authors personal experience from working at the scene during the event and several other personal testimonies were also included in this analysis. RESULTS: Totally 2,762 death certificates were issued by the state of New York for victims of the terror attack. 1,361 (49.9%) of these were issued for victims whose remains could not be identified. All but nine of these victims died at the day of the attack. 77% of the victims were male, medium age 39 years. Of the dead were 342 fire fighters and paramedics and 60 police officers. A total of 1,103 patients were treated during the first 48 days in five key hospitals receiving the majority of the injured. 29% of these were rescue workers. 66% of the injured were male, average age 39 years. The most common injuries were respiratory impairment (49%) and ocular affection (26%), many severe. The most common trauma was lacerations (14%) and sprains (14%). Of those administered to hospital, 19% had trauma and 19% burns. Head injuries were registered in 6% and crush injuries in 4%. With regard to response from involved agencies, communication failure was the most common and difficulties in command operations and scene control were also prevalent. CONCLUSIONS: The difficulties encountered were very similar to those commonly seen in major accidents or disasters, although on a great scale. Response plans have to be critically reviewed based on the experiences from this and other events, in order to pre-empt difficulties such as those described here in future responses to major urban accidents and disasters. PMID- 26814900 TI - Incidence, Cause and Treatment of Burn Casualties Under War Circumstances. AB - Five to ten percent of all combat injuries in the last decade of armed conflicts have been burns. Here, the incidence, demographics, and treatment are different compared to civilian practice. The percentage of hand and facial burns is higher, the population of patients is healthier, there are more associated injuries, and the transportation time is longer. Due to the prolonged transportation time, emergency treatment and also intermediate treatment are important for a good outcome in patients with burns suffered in a military environment. Treatment guidelines and education of the involved medical personnel according to the findings described herein are important for better results in future combat casualties. PMID- 26814901 TI - US Trauma Center Preparation for a Terrorist Attack in the Community. AB - BACKGROUND: Since the 2001 terrorist attacks on the United States, federal and state funding, primarily from the National Bioterrorism Hospital Preparedness Program, has resulted in a surge of hospital activity to prepare for future natural or human-caused catastrophes. Trauma centers were integrally involved in the response to the 2001 attacks as first receivers of patients, communication hubs, and as convergence sites for families, the worried well, volunteers, and donors. After the Madrid train station terrorist attack, Congress identified the need to study trauma center preparedness as an essential part of the nation's emergency management system. METHODS: The NFTC received a one-year grant funded by the Centers for Disease Control and Prevention (CDC/NCIPC) to survey the capability and capacity of trauma centers to respond successfully to mass casualty incidents, particularly those brought about by acts of terrorism. This report summarizes responses to a US CDC/NCIPC-funded survey, R 49 CE000792-01, sent to all designated or verified Level I and II trauma centers in the US, to which 33% or 175 trauma centers replied. RESULTS: The results are categorized by preparedness scoring, vulnerability, threats, and funding. Planning communication, surge capacity, diversion, sustainability, special populations, and finance represent additional categories examined in the survey. CONCLUSIONS: Trauma centers are a major resource in disaster management. One-hundred and seventy-five centers candidly reported their resources and vulnerabilities. This inventory should be expanded to all trauma centers and recommendations for change as discussed. PMID- 26814899 TI - Role of Selective Management of Penetrating Injuries in Mass Casualty Incidents. AB - Terrorist violence has emerged as an increasingly common cause of mass casualty incidents (MCI) due to the sequelae of explosive devices and shooting massacres. A proper emergency medical system disaster plan for dealing with an MCI is of paramount importance to salvage lives. Because the number of casualties following a MCI is likely to exceed the medical resources of the receiving health care facilities, patients must be appropriately sorted to establish treatment priorities. By necessity, clinical signs are likely to prove cornerstones of triage during MCI. An appropriate and effective application of experiences learned from the use of selective nonoperative management (SNOM) techniques may prove essential in this triage process. The present appraisal of the available literature strongly supports that the appropriate utilization of these clinical indicators to identify patients appropriate for SNOM is essential, critical, and readily applicable. We also review the initial emergent triage priorities for penetrating injuries to the head, neck, torso, and extremities in a mass casualty setting. PMID- 26814902 TI - Coordination of Emergency Medical Services for a Major Road Traffic Accident on a Swiss Suburban Highway. AB - On 9th April 2008 at 2:14 p.m., on the highway between Lausanne and Vevey in western Switzerland, there was a 72-car pileup including five trucks that caused one death and injured 26 others. The relatively light toll was attributed to reduced vehicular speeds on account of foggy weather, together with the quick actions and effectiveness of the first responders and the excellent collaboration between the various rescue groups (medical rescue services, fire and police departments). For the first time, we used an innovative on-site medical command and control system, based on a binomial team. Two hours after the accident, the last of the injured had been evacuated and first aid on the site had ended. This article describes how the Emergency Medical Services from the State of Vaud, Switzerland, handled the situation and how the binomial team is structured. PMID- 26814903 TI - Minimally Invasive Anterior Plate Osteosynthesis in Humeral Shaft Fractures. AB - Twelve patients with shaft fractures of the humerus were treated with percutaneous anterior plate osteosynthesis using a deltoid-pectoral respectively brachialis splitting approach without exposure of the radial nerve. The implants used were PHILOS plates, locking compression plates 3.5 and 4.5, and a tibial metaphyseal plate (all by Synthes). There were no intraoperative complications, no infections and no iatrogenic injuries of the radial or axillary nerve. Nine fractures healed entirely. There was one pseudarthrosis caused by a plate that was too short; another fracture probably healed but the distal screws broke; and one patient was lost to follow-up. Minimally invasive anterior plate osteosynthesis in humeral shaft fractures is an operative alternative which may be indicated not only in delayed healing or complex shaft fractures. PMID- 26814904 TI - A Prospective Study of Penetrating Abdominal Trauma at the University of Calabar Teaching Hospital, Calabar, Southern Nigeria. AB - BACKGROUND: Abdominal injuries are on the increase in both developed and developing countries. The frequency of penetrating abdominal trauma (PAT) varies across the globe because it relates to industrialization, the weapons available, and the presence of military conflicts. This study sought to evaluate the current pattern and outcome of managementof PAT in Calabar, which is undergoing rapid urbanization, and with a focus on tourism. METHOD: Patients admitted to the University of Calabar Teaching Hospital, Calabar with PAT from February 2005 to January 2008 were prospectively studied. RESULTS: Seventy-nine patients presented with abdominal trauma, among which 39 (49%) were PAT. There were 37 males and two females, whose ages ranged from 5 to 54 years (mean 27.8 years). Stab wound (18; 46.1%) was the commonest injury, while gunshot wound (15; 38.5%) ranked second. Others were road traffic accident (two patients), fall, cow horn injury, shrapnel, and criminal abortion (a patient each). The commonest injury was evisceration of the omentum and small intestine, which occurred in 13 (36%) patients. Five (14%) patients suffered small intestinal perforations, while three (8%) had liver, splenic and colonic injuries, respectively. Others were rectal injury (four patients), mesenteric injury and perforated stomach (two patients each), and a patient with diaphragmatic injury. The outcome was fatal in two (5%) patients. CONCLUSION: Penetrating abdominal trauma is on the increase in Calabar. The pattern of injury revealed areas which, when effectively contained, will lead to an improvement in the safety of our environment. PMID- 26814905 TI - Bone Mineral Density is Not Correlated with One-Year Functional Outcome in Distal Radial Fractures: A Preliminary Study. AB - INTRODUCTION: The intrinsic stability of fractures related to soft tissue injury and the comminution of the metaphyseal part of the distal radius influence the chance of secondary displacement in distal radial fractures treated conservatively. A low bone mineral density may also contribute to this secondary displacement and could therefore play a role in functional outcome. This possible relation between functional outcome and bone mineral density is poorly studied. PATIENTS AND METHODS: Patients with a unilateral conservatively treated distal radial fracture were assessed one year after their fracture with the DASH score (disabilities of the arm, shoulder and hand) and the Cooney score. Fractures were classified according to the AO classification. Radial inclination, radial shift, radial tilt and ulnar variance were measured on the first and follow-up radiographies. Bone mineral densities of both the hip and lumbar spine were measured by DXA and expressed as T-scores. RESULTS: Fifty-four patients participated in this study (mean age 68 years). Osteoporosis (T-score <= -2.5) was present in 20 patients (37%), osteopenia (T-score of -1 to -2.5) in 30 patients (56%), and normal bone density (T-score > -1) in four patients (7%). The distribution of fracture types according to the AO classification showed 32 A type fractures, eight B-type fractures and 14 C-type fractures. Both univariate linear and multivariate regression analysis with covariates of age, sex, body mass index and AO classification showed no significant correlation between T score and functional outcome. CONCLUSION: The functional outcome of conservatively treated distal radial fractures in this study does not correlate with bone mineral density. Therefore, BMD measurement cannot be used to predict functional outcome in these patients. PMID- 26814906 TI - Warfarinized Patients with Proximal Femoral Fractures: Survey of UK Clinical Practice. AB - INTRODUCTION: In an aging population, anticoagulation in patients with musculoskeletal injuries is increasingly prevalent. The North American literature indicates an absence of consensus concerning the most appropriate management for this group. We aim to test the hypothesis that there is a lack of consensus in the UK regarding the perioperative management of patients with hip fractures on long-term warfarin therapy. MATERIALS AND METHODS: A representative group of 400 consultant orthopedic surgeons was surveyed by postal questionnaire regarding their policy on the reversal of anticoagulation in warfarinized patients with hip fractures. The consultants contacted were selected to represent a geographical spread throughout the UK. RESULTS: There were 159 respondents (40% response rate), of which 79% (126) had a trauma commitment. 95 (75%) of these had a protocol for the reversal of anticoagulation prior to surgery. The commonest method used was to simply withhold warfarin and wait (70%). Other methods included FFP (16%), and low-dose (23%) and high-dose (14%) vitamin K. Some respondents used more than onemethod. Although nearly all respondents preferred an INR < 2.0 prior to surgery, 55% preferred an INR < 1.5. DISCUSSION: Hip fracture in the presence of long-term warfarin use is associated with significantly increased morbidity. This problem is likely to increase. Our results demonstrate variation in approach throughout the UK with regard to warfarin reversal and the acceptable INR at which to operate in this group of patients. We propose that low-dose vitamin K is considered more widely as a safe and effective method of warfarin reversal in this group. PMID- 26814907 TI - Clopidogrel and Proximal Femoral Fractures: Does Timing of Surgery Affect Blood Loss and Length of Admission? A Preliminary Study Prior to Multicenter Trial. AB - INTRODUCTION: Clopidogrel is a potent oral antiplatelet agent that is commonly prescribed to patients with cardiovascular disease. Patients presenting with proximal femoral fractures often have cardiovascular comorbidity, with many taking clopidogrel on admission. Scientific literature reports increased surgical bleeding in patients receiving clopidogrel, though not specifically hip surgery. This study looked at whether patients who had a seven-day delay prior to operative treatment had less bleeding than those who did not, and looked at the differences in length of admission between the two groups. METHODS: A retrospective review was undertaken. Patients were identified from the in-patient pharmacy stock records from July 2005 to July 2006. Data was statistically analyzed using the chi-squared test. RESULTS: Of 21 patients identified, 20 met the inclusion criteria, nine had a seven-day delay before operation (Group A), and 11 had a mean one-day delay (Group B). Mean drop in postoperative hemoglobin was 1.8 g/l in Group A compared to 3.1 g/l in Group B (p < 0.05). Number of complications was similar (Group A = 8 vs. Group B = 9) as was mortality (Group A = 1 vs. Group B = 2). Admission length was longer in patients who had a seven-day delay in surgery (Group A = 32 vs. Group B = 22 days) (p < 0.05). CONCLUSION: Patients should be considered for early operation provided there are no additional bleeding risk factors, as although postoperative hemoglobin is lower, mortality and complication rates are similar, and length of admission is shorter. PMID- 26814908 TI - Monteggia and Monteggia-like-lesions: Classification, Indication, and Techniques in Operative Treatment. AB - Monteggia fractures consist of an ulna fracture accompanied by radial head dislocation. Such fractures are easily overlooked due to the prominence of the ulna fracture. Earlier studies have reported on the results of treating Monteggia fractures in children and adults even though this type of fracture is different in these two patient populations. As such they should be considered as separate entities due to the different injury pattern, the prognosis, and the preferred method of treatment. For a good postoperative result, an early detection of the Monteggia dislocation, an efficient operative treatment of the ulna fracture, and reposition of the radial head are essential. The goal of reconstruction is an early mobilization within a stable arc of motion. Here, we provide an overview of the classification of Monteggia fractures, the mechanism of injury, and treatment options with the aim of providing sufficient information to reduce the possibility of underestimating forearm injuries in adults. PMID- 26814909 TI - Injury to the Thoracic Aorta Following Fatal Blunt Trauma: An Autopsy Study. AB - BACKGROUND: Transection of the thoracic aorta (TTA) remains a leading cause of death after blunt trauma. In this autopsy study, the natural history of this injury is reviewed. PATIENTS AND METHODS: All blunt trauma deaths that occurred in the Milano urban area over a period of one year were collected. Autopsies were available in all cases. Incidence, mechanisms, anatomical locations of TTA, deaths due to TTA or coexisting injuries, and times of death were reviewed. Cause of death was established. Death was attributed to TTA if its abbreviated injury score was six (hemorrhage not confined to the mediastinum). RESULTS: 199 cases of fatal blunt trauma were included, 72% of which were males; mean age 53 +/- 21. A TTA was observed in 53 subjects (27%), with a significantly higher incidence between the ages of 45 and 64 years and after falls from height. The aorta was transected at the isthmus in 36% of cases. Victims with TTA had a higher pre hospital mortality and more injuries to chest organs, the chest wall and pelvis. In victims with TTA, injury to the aorta was the cause of death in 58%. Only five patients with TTA survived more than 1 h, reaching the hospital alive; four of these died due to the rupture of a mediastinal hematoma during the first hours of in-hospital care. CONCLUSIONS: This study demonstrates that TTA is a frequent cause of immediate deaths among blunt trauma victims. Patients with risk factors for TTA who reach the hospital alive need to be promptly investigated with a contrast CT scan. Evidence of mediastinal hematoma is suggestive for possible rapid evolution. PMID- 26814910 TI - A Lethal Case of Fat Embolism Syndrome in a Nine-Year-Old Child: Options for Prevention. AB - We report a lethal case of fat embolism syndrome in a nine-year-old child after a direct blunt trauma leading to a pelvic fracture. On the second day, signs of bowel perforation and septic shock led to an acute aggravation of the pulmonary symptoms, cardiac arrest and death. Fat embolism is seldom thought to occur in pediatric trauma patients; however, this case illustrates it can lead to disastrous sequela. Since there is no specific treatment for it, prevention by early fracture stabilization is the only option. PMID- 26814911 TI - Volkmann Ischemic Contracture Due to Traditional Practice. AB - An 11-year-old boy presented with three days' history of blunt trauma to the left shoulder due to a fall to the ground. The boy was taken to the traditional practitioner, who applied a very tight bandage over a piece of cartoon on the upper left humerus, which resulted in progressive pain and swelling of the whole left upper limb and impairment of movement and sensation. The tight bandage was removed after 48 h and fasciotomy was performed at Aljamhuri Hospital in Taiz, Yemen. The child was brought to our hospital after the family was informed about the need for left forearm amputation. We performed four sessions of debridement of the dead muscles and soft tissues of the flexor and extensor compartments of the left upper limb. After three months, the left upper limb healed with fixed flexor contracture of the elbow and wrist joint. Manipulation and release of adhesions and subsequent skin grafting was performed and the elbow joint was kept in extension, the wrist in the neutral position, and the interphalangeal joints in flexion. Although the limb was saved, its aesthetic appearance was retained, and some sensation was achieved, the lost motor function of the forearm (including the hand) was irreversible. PMID- 26814912 TI - Chance Fracture of the Upper Thoracic Spine in a Child. AB - We report on a three-year-old girl who fell accidentally from the fourth floor. She suffered multiple trauma, including severe head injury, unstable T2-T3 Chance fracture, pneumothorax with lung contusion and serial rib fractures on the left side, liver laceration, splenic injury and fracture of the sacral bone on the right side. The progressive intracranial pressure was released by trepanation and bifrontal craniectomy. The abdominal injuries were treated conservatively. After stabilization of the intracranial situation, dorsal spondylodesis from T2 to T4 was performed employing the cannulated NEON system (Ulrich((r))) with CT controlled positioning of guide wires. One year on, the implants have been removed and the patient has good function, with only a small atactic dysfunction as residuum. To our knowledge, this is the first report of a pediatric Chance fracture located in the upper thoracic spine following a fall from great height that describes how this treatment approach led to a very favorable outcome. PMID- 26814913 TI - Abstracts : 28th Meeting of the Pediatric Section of the German Society of Trauma Surgeons (DGU), June 19-20, 2009 Mannheim, Germany. PMID- 26814914 TI - Necrobiotic xanthogranuloma associated with monoclonal gammopathy: successful treatment with lenalidomide and dexamethasone. PMID- 26814915 TI - The absorption, distribution, metabolism and excretion of procyanidins. AB - Procyanidins (PAs) are polyphenols in plant food that have many health benefits, including cancer prevention, cardiovascular protection and diabetes prevention. PAs have been known to have low oral bioavailability. In this review, we summarize the published results on the ADME (absorption, distribution, metabolism and excretion) of PAs in vivo and in vitro. After oral administration, in the stomach the decomposition of PAs is highly dependent on the pH value of gastric juice, which is also affected by food intake. In the small intestine, PA polymers and oligomers with DP > 4 are not directly absorbed in vivo, but minor PA monomers and dimers could be detected in the plasma. Methylated and glucuronidated PA dimers and monomers are the main metabolites of PAs in plasma. In the colon, PAs are catabolized by colonic microflora into a series of low molecular weight phenolic acids, such as phenyl valerolactone, phenylacetic acids and phenylpropionic acids. We reviewed the degradation of PAs in gastric digestion, the absorption of PAs in the small intestine and the metabolic pathway of PAs by colonic microflora. To clearly explain the in vivo pharmacokinetics of PAs, a systematic comparative analysis on previously published data on PAs was conducted. PMID- 26814916 TI - Quality improvement in trauma care. PMID- 26814917 TI - History, development and future of trauma care for multiple injured patients in the Netherlands. AB - INTRODUCTION: The development of trauma systems all over the world resulted in improved outcome for a broad range of trauma victims. In this review, we demonstrate the developments of an inclusive regionalised trauma system in the Netherlands and the subsequent developments in our level one trauma centre and trauma region in comparison. COMPARISON WITH OTHER TRAUMA SYSTEMS: With the seasoning of the trauma system, further improvements in outcome could be demonstrated, in the region an OR of 0.84 and in the trauma centre an OR of 0.61, in a later comparison over the years another OR 0.74 was noted. In addition, a further diversification of the trauma populations was seen in the various hospitals with different levels, based on a pre-hospital triage system. Torso and multiple injured patients were more seen in the trauma centre and increased to more than 350 patients with an ISS of >15, whereas monotrauma was almost exclusively seen in the level two and three hospitals. The further development of the trauma system is discussed, in which the minimum requirements of the individual trauma surgeon and institution are taken as a guideline. FUTURE, DISCUSSION AND CONCLUSION: Based on these considerations, a further concentration of the most severely injured patients is proposed in a small country as the Netherlands culminating in one trauma centre for the most severely injured patients, combined with an integrated pre-hospital helicopter system, on top of the current good functioning inclusive trauma system. These developments could be a template for further developments of trauma systems in Europe. PMID- 26814918 TI - Ultrasonographic diagnosis of abdominal free fluid: accuracy comparison of emergency physicians and radiologists. AB - OBJECTIVE: Blunt abdominal trauma is a diagnostic challenge for emergency physicians and ultrasonography is one of the diagnostic tools used in this type of injuries. The aim of this study was to evaluate the diagnostic value of ultrasonographies performed by emergency physicians and radiologists. METHODS: This prospective diagnostic study was performed in the emergency departments of two trauma centers in Iran during a period of 12 months. The subjects were all patients with blunt abdominal trauma that were candidated for abdominopelvic computed tomography (CT) scanning in our emergency departments. The results of focused assessment with sonography for trauma (FAST) performed by emergency physicians and radiologists were compared blindly with the results of CT scans performed by radiologists. The sensitivity, specificity, and predictive values of diagnosis for different abdominal anatomic areas were calculated. RESULTS: In total, 450 patients undergoing FAST and CT scanning were studied. The sensitivity of radiologists' diagnoses for Morison's, splenorenal, perivesical, and pleural effusion areas were, respectively, 88.0, 70.0, 38.0, and 30.0 %. The corresponding values for emergency physicians' diagnoses were, respectively, 82.0, 60.0, 28.0, and 30.0 %. The specificity of radiologists' diagnoses in the mentioned areas were, respectively, 98.9, 100, 93.1, and 100 %, and for emergency physicians, they were, respectively, 98.9, 100, 96.0, and 100 %. CONCLUSION: Emergency physicians showed a promising performance in applying FAST in blunt abdominal trauma. The specificity of ultrasonographic diagnosis in the emergency physicians group and the radiologists group were comparable, while radiologists showed a higher performance regarding the sensitivity of the ultrasonographic diagnosis. PMID- 26814920 TI - Serial lactate and admission SOFA scores in trauma: an analysis of predictive value in 724 patients with and without traumatic brain injury. AB - OBJECTIVE: Arterial lactate, base excess (BE), lactate clearance, and Sequential Organ Failure Assessment (SOFA) score have been shown to correlate with outcome in severely injured patients. The goal of the present study was to separately assess their predictive value in patients suffering from traumatic brain injury (TBI) as opposed to patients suffering from injuries not related to the brain. MATERIALS AND METHODS: A total of 724 adult trauma patients with an Injury Severity Score (ISS) >= 16 were grouped into patients without TBI (non-TBI), patients with isolated TBI (isolated TBI), and patients with a combination of TBI and non-TBI injuries (combined injuries). The predictive value of the above parameters was then analyzed using both uni- and multivariate analyses. RESULTS: The mean age of the patients was 39 years (77 % males), with a mean ISS of 32 (range 16-75). Mortality ranged from 14 % (non-TBI) to 24 % (combined injuries). Admission and serial lactate/BE values were higher in non-survivors of all groups (all p < 0.01), but not in patients with isolated TBI. Admission SOFA scores were highest in non-survivors of all groups (p = 0.023); subsequently septic patients also showed elevated SOFA scores (p < 0.01), except those with isolated TBI. In this group, SOFA score was the only parameter which showed significant differences between survivors and non-survivors. Receiver operating characteristic (ROC) analysis revealed lactate to be the best overall predictor for increased mortality and further septic complications, irrespective of the leading injury. CONCLUSION: Lactate showed the best performance in predicting sepsis or death in all trauma patients except those with isolated TBI, and the differences were greatest in patients with substantial bleeding. Following isolated TBI, SOFA score was the only parameter which could differentiate survivors from non-survivors on admission, although the SOFA score, too, was not an independent predictor of death following multivariate analysis. PMID- 26814921 TI - Prehospital care in patients with severe traumatic brain injury: does the level of prehospital care influence mortality? AB - INTRODUCTION AND PURPOSE: The controversy between the "scoop and run" versus the "stay and play" approach in severely injured trauma patients has been an ongoing issue for decades. The present study was undertaken to investigate whether changes in prehospital care for patients with severe traumatic brain injury in the Netherlands have improved outcome. METHODS: In this retrospective study, files (n = 60) were analyzed from a prospectively collected database including all patients admitted to one of six hospitals in the Limburg region in the Netherlands with a Glasgow Coma Scale (GCS) score <=8 on admittance over the period from January 2006 to December 2008. All patients had traumatic brain damage proven on computed tomography (CT) or magnetic resonance imaging (MRI). Relevant prehospital and clinical data from the present cohort were compared to data from a similar study (n = 30) conducted 20 years ago. The primary outcome assessed was mortality. RESULTS: The two study groups had similar characteristics with regard to the GCS score. In the historic cohort, Basic Life Support (BLS) and the "scoop and run" approach in patients with major traumatic brain injury was common, with an average time on scene of 7.5 min. Currently, prehospital care is performed mainly on the level of prehospital Advanced Life Support (ALS), with the average time on scene being about four times as long as in the historic cohort. However, the overall mortality rate for the current cohort compared to the historic cohort has not changed. CONCLUSION: Despite more on-site ALS in severely head injured patients nowadays compared to the historic cohort, there was no reduction in mortality. PMID- 26814922 TI - Occult hemopneumothorax following chest trauma does not need a chest tube. AB - BACKGROUND: The increasing use of thoracic computed tomography (CT) in trauma patients has led to the recognition of intrapleural blood and air that are not initially evident on admission plain chest X-ray, defining the presence of occult hemopneumothorax. The clinical significance of occult hemopneumothorax, specifically the role of the tube thoracostomy, is not clearly defined. OBJECTIVE: To identify those patients with occult hemopneumothorax who can be safely managed without chest tube insertion. DESIGN: Prospective observational study. METHODS: During the recent 24 month period ending July 2010, comprehensive data on trauma patients with occult hemopneumothorax were recorded to determine whether tube thoracostomy was needed and, if not, to define the consequences of nondrainage. Pneumothorax and hemothorax were quantified by computed tomography (CT) measurement. Data included demographics, injury mechanism and severity, chest injuries, need for mechanical ventilation, indications for tube thoracostomy, hospital length of stay, complications and outcome. RESULTS: There were 73 patients with hemopenumothorax identified on CT scan in our trauma registry. Tube thoracostomy was successfully avoided in 60 patients (83 %). Indications for chest tube placement in 13 (17 %) of patients included X-ray evidence of hemothorax progression (10), respiratory compromise with oxygen desaturation (2). Mechanical ventilation was required in 19 patients, five of them required chest tube insertion, and six developed ventilator associated pneumonia, while there were no cases of empyema. There was one death due to severe head injury. CONCLUSIONS: Occult hemopneumothorax can be successfully managed without tube thoracostomy in most cases. Patients with a high ISS score, need for mechanical ventilation, and CT-detected blood collection measuring >1.5 cm increased the likelihood of need for tube thoracostomy. The size of the pneumothorax did not appear to be significant in determining the need for tube thoracostomy. PMID- 26814919 TI - Whole body imaging in the diagnosis of blunt trauma, ionizing radiation hazards and residual risk. AB - Ever since the introduction of radiographic imaging, its utility in identifying injuries has been well documented and was incorporated in the workup of injured patients during advanced trauma life support algorithms [American College of Surgeons, 8th ed. Chicago, 2008]. More recently, computerized tomography (CT) has been shown to be more sensitive than radiography in the diagnosis of injury. Due to the increased use of CT scanning, concerns were raised regarding the associated exposure to ionizing radiation [N Engl J Med 357:2277-2284, 2007]. During the last several years, a significant amount of research has been published on this topic, most of it being incorporated in the BEIR VII Phase 2 report, published by the National Research Council of the National Academies [National Academy of Sciences, Washington DC, 2006]. The current review will analyze the scientific basis for the concerns over the ionizing radiation associated with the use of CT scanning and will examine the accuracy of the typical advanced trauma life support work-up for diagnosis of injuries. PMID- 26814923 TI - Abdominal vascular trauma in 760 severely injured patients. AB - PURPOSE: The relevance of abdominal vascular injuries in polytraumatic patients within a large collective has not yet been thoroughly analyzed. This study aimed at assessing the prevalence of traumatic injuries in relation to outcome and currently established treatment options. METHODS: 51,425 patients from the Trauma Registry of the German Society of Trauma Surgery (TR DGU) (1993-2009) were analyzed retrospectively. All patients who had an Injury Severity Score (ISS) of >=16, were directly admitted to a trauma center and subsequently received treatment for at least three days, were >=16 years old, and had an abdominal injury (AISabdomen >=2) were included. Patients with abdominal trauma (AISabdomen >=2) were compared with patients with additional vascular trauma (AISvascular 2 5). RESULTS: 10,530 (20.5 %) of the 51,425 patients had documented abdominal injury. 760 (7.2 %) of the patients with abdominal injury additionally showed abdominal vascular injury (AISabdomen >=2, AISvascular 2-5) and were analyzed based on the classification of the American Association for the Surgery of Trauma (AAST) organ severity score (AAST vascular injury grade: II, 2.4 %; III, 2.7 %; IV, 1.8 %; V, 0.2 %. Patients with high-grade abdominal vascular injury (grades IV and V) showed a significant increase in mortality (IV, 44.6 %; V, 60 %) and consequently a decrease in the need for surgical intervention (IV, 67.4 %; V, 64 %). CONCLUSIONS: The results presented here show the prevalence and outcome of abdominal vascular injuries in a large collective within the TR DGU for the first time. Based on the current literature and these findings, a treatment algorithm has been developed. PMID- 26814924 TI - Evaluation of current treatment regimens for prepatellar and olecranon bursitis in Switzerland. AB - PURPOSE: Bursitis is a common entity. However, evidence for the best treatment procedures is lacking, with management concepts varying internationally. We evaluated current treatment regimens for septic (SB) and nonseptic (NSB) prepatellar (PB) and (OB) olecranon bursitis in Switzerland and compared them to the published literature. METHODS: A voluntary 23-item online survey was distributed amongst all registered Swiss infectiologists and orthopedic surgeons in December 2011. The literature comparison was based on a systematic literature review. RESULTS: Overall response rate was 14 % (n = 117); 11 % (n = 92) were included in the final analysis. The overwhelming majority (91 %) of the respondents differentiated between SB and NSB, with determination predominantly based on clinical presentation (83 %), blood chemistry (75 %), and bursal aspirate (66 %). NSB was predominantly treated conservatively via immobilization (78 %) and anti-inflammatory medication (73 %). For SB, 85 % indicated surgical intervention, with 73 % prescribing concomitant antibiotics. Regarding antibiotic choice, 90 % used an aminopenicillin or its derivatives for a mean of 11 +/- 5 days. The literature review revealed 66 relevant publications with an overall level of evidence of 2b, arguing for a conservative treatment approach in cases of SB or NSB. CONCLUSION: Therapeutic regimens for OB/PB differed considerably within Switzerland. Surgical intervention and antibiotic treatment was the most common therapy for SB, whereas a conservative approach predominated for NSB, which contrasts with the international literature. Clearly, prospective multicenter and multidisciplinary studies are needed to identify an optimal and cost-saving approach to the treatment of these common clinical entities. PMID- 26814925 TI - Reamed intramedullary nailing of diaphyseal tibial fractures: comparison of compression and non-compression nailing. AB - BACKGROUND: Modern intramedullary implants provide the option to perform compression at the fracture gap in long bone fractures via a compression screw mechanism. The aim of this study was to assess if the application of interfragmentary compression in the intramedullary nailing of tibia fractures could increase the union rate and speed of fracture healing. METHODS: Sixty-three patients who suffered from an AO-type 42-A3 or 42-B2 fracture that was treated by reamed intramedullary nailing between 2003 and 2008 were included in this retrospective study. Twenty-five patients were treated with dynamic interlocking without compression while 38 were treated with compression nailing. The compression load of the dynamic proximal screw was calculated by postoperative X ray and radiographs taken four weeks after operation. Healing was assessed by radiological evaluation until the completion of bony healing or the disappearance of clinical symptoms. Nonunion was defined as the absence of radiological union and the persistence of clinical symptoms after six months. RESULTS: Postoperative compression was applied at a mean load of 1,852 N, and 980 N remained after four weeks. In the compression group, 19 open and 19 closed fractures occurred. In the non-compression group, 25 patients were included (14 closed and 11 open cases). Active compression decreased healing time significantly. Nonunion occurred in one compression patient and three non-compression patients. CONCLUSION: The results show that additional compression of the fracture gap can improve healing outcome in simple transverse tibial shaft fractures treated with reamed nailing. PMID- 26814927 TI - A new fixation method for Hoffa fracture. AB - PURPOSE: To investigate the clinical effect of a new fixation method for Hoffa fractures. METHODS: We treated eleven patients with Hoffa fracture using the new fixation method (fixation with one screw inserted from the femoral intercondylar notch and two screws inserted from the nonarticular lateral (or medial) surface of the fractured condylar fragment; the two sets of screws were crossed). RESULTS: After an average follow-up period of 24 months (range 5-28 months), all fractures had healed. The average healing time was 11.6 weeks (range 9-14 weeks). On the version of the Knee Society Score modified by Dr. John Insall in 1993, the average score was 174.6 points (range 125-199 points). CONCLUSIONS: The new fixation method for Hoffa fracture is effective, and may provide a new way to treat Hoffa fractures. PMID- 26814926 TI - The prognostic reliability of the Glasgow coma score in traumatic brain injuries: evaluation of MRI data. AB - PURPOSE: To clarify the predictive power of the Glasgow coma score (GCS) after traumatic brain injury (TBI) and in the context of brain stem lesions. METHODS: In 143 patients who had suffered severe TBI, the GCS was correlated to brain damage as visualized by cranial magnetic resonance imaging (MRI). This technique evaluates the damage to the brain stem in particular. The Brussels coma score (BCS) was also used. RESULTS: The GCS was not significantly correlated to brain stem lesions when it was only scored at the time of admission. When MRI was not used later on, the GCS showed a poor ability to predict the outcome. After 24 h, and on the day of MRI screening, the GCS was significantly correlated with two parameters: outcome (the higher the GCS, the better the outcome) and the frequency of patients without injuries to the brainstem in MRI (the higher the GCS, the higher this frequency). These correlations were much more evident when the BCS was used. The prognostic power of the GCS was found to vary over time; for example: a GCS of 3 at admission was associated with a favorable prognosis; a GCS of 4 signified a poor prognosis, irrespective of the time point at which the GCS was scored; and the prognostic power of a GCS of 5 deteriorated from the day of the MRI onwards, whereas the prognostic power of a GCS of 6 or 7 varied little over time. CONCLUSIONS: We only recommend the use of the GCS for prognostic evaluation in a multidimensional model. Study protocols should contain additional brain stem function parameters (BCS, pupil condition, MRI). PMID- 26814929 TI - Message from the President. PMID- 26814930 TI - Poly(A) Extensions of miRNAs for Amplification-Free Electrochemical Detection on Screen-Printed Gold Electrodes. AB - Current amplification-based microRNA (miRNA) detection approaches are limited by the small sizes of miRNAs as well as amplification bias/artifacts. Herein, we report on an amplification-free miRNA assay based on elevated affinity interaction between polyadenylated miRNA and bare gold electrode. The poly(A) extension on the 3' ends of magnetically isolated miRNA targets facilitated high adsorption efficiency onto gold electrode surfaces for electrochemical detection without any cumbersome electrode surface functionalization procedures. The assay showed excellent detection sensitivity (10 fM) and specificity and was demonstrated for quantitative miR-107 detection in human cancer cell lines and clinical urine samples. We believe our assay could be useful as an amplification free alternative for miRNA detection. PMID- 26814928 TI - A practical therapeutic protocol for cervical tuberculosis. AB - PURPOSE: Cervical tuberculosis (CTB) is a relatively rare entity, even in endemic countries. Currently, management ranges from conservative to radical surgical approaches. We report our experience in diagnosing and treating 66 cases of CTB in the past eight years using our CTB therapeutic protocol. METHODS: All patients diagnosed with CTB were followed up over a 3.5-year period. Patients were divided into three grades using clinicoradiological criteria designed to evaluate the initial severity of the disease. Overall performance status was assessed based on the American Spinal Injury Association (ASIA) scale. Neurological recovery was evaluated with the ASIA scale as well as using X-rays and computed tomography every four weeks for the initial three months and every three months thereafter. RESULTS: The mean follow-up duration was 38.2 +/- 6.2 months. No mortality occurred. One case of recurrence due to irregular antitubercular treatment (ATT) was cured by abscess clearing and regular ATT. All other patients had good clinicoradiological outcomes, regardless of grading. CONCLUSIONS: The use of our proposed scoring system and management protocol allowed speedy management of CTB. PMID- 26814931 TI - Focus on Spinal Injuries in Multiple Trauma Patients. PMID- 26814932 TI - Distribution of Spinal and Associated Injuries in Multiple Trauma Patients. AB - Injury to the spinal column and cord are often part of life-threatening multiple trauma. Epidemiological data could help to establish an evidence-based assessment and therapy of these patients. We present a retrospective chart analysis of 590 multiple traumatized patients admitted within a 4-year-period. Patients suffering from injuries of the spinal column were analysed regarding mechanism and distribution of their injuries to all body regions. Thirty-one percent (n = 183) of polytraumatized patients displayed a spine injury. Distribution analysis showed peaks in the cervical spine and the thoraco-lumbar junction. The risk of relevant associated injuries is mainly influenced from anatomical vicinity to the injured spinal segment. Injuries to the spinal column are frequent in the multiple trauma patients population. Diagnosed injuries to distinct body regions should make the trauma team suspicious of injury to the nearby spinal column. Appropriate treatment includes thorough assessment of all injuries to clarify the damage and carry on special protection of these spinal regions preventing from deterioration. PMID- 26814933 TI - Combined Abdominal and Spine Injuries after High Energy Flexion-Distraction Trauma. AB - Combined abdominal (AT) and spine (ST) trauma in the multiply traumatized patient (MT) requires optimal clinical management. At the Traumacenter Murnau, Germany all multiply injured patients (injury severity score >= 16) are registered in a large prospective database (DGU-Tramaregister). From 1 January 2002 until 31 December 2004, 731 multiply injured patients (ISS >= 16) were admitted to the Trauma Center Murnau. In this population, ST was diagnosed in 287 patients (39%), AT was diagnosed in 100 patients (14%), and in 35 patients (5%) a combined ST and AT was observed. The most frequent injury mechanism in patients with a combined ST and AT was high-energy flexion-distraction trauma caused by motor vehicle accident with seat belt fastened passengers, bicycle accident, and fall from great height. In the cohort group of 35 patients, 29 required either abdominal or spinal operation. In 23 patients the AT and in 18 patients the ST necessitated operation. In 14 patients both the AT and ST called for surgery. The AT was predominately treated with splenectomies, resections and suturing of the intestine. The ST resulted in 14 posterior and four postponed anterior stabilizations of the thoracolumbar and four anterior fusions of the cervical spine. Mean age of these patients was 37 years in comparison to 47 years in the control group (MT without combined AT and ST). ISS of patients with combined AT and ST was 38 points compared to 26 points in the control group, and mortality was 7% in the combined group compared to 14% in the control group. The present study documents that damage control principles applied to patients sustaining the complex combination of AT and ST can result in low mortality rates despite the severity of this injury. PMID- 26814934 TI - Operative Timing and Management of Spinal Injuries in Multiply Injured Patients. AB - Spinal injuries occurring in polytrauma patients are caused by high impact trauma. Due to high velocity mechanism, trauma of the vertebral column may be accompanied by injuries of adjacent body cavities such as thorax, abdomen, and pelvis. Neurologic examination is mandatory and has to be documented preferably using the ASIA/IMSOP-classification. Clinical symptoms may point towards spinal injury. However, absence of clinical symptoms is not sufficient to rule out spinal injuries. Two diagnostic pathways may be followed to assess the spine: (1) Conventional X-ray diagnostics of the entire spine followed by selective CT scanning of suspected lesions and CT scanning of the upper cervical spine region C0-C3 in unconscious patients. (2) Whole body polytrauma-multislice-spiral-CT scanning from head to pelvis without conventional Xray playing the key role in the algorithm of modern ER management. In this study, 287 polytrauma patients with associated spinal injuries were analyzed prospectively from a cohort group of 731 polytrauma patients treated from 2002 to 2004 in our institution. Indications for surgery include neurologic deficit, instability, as well as malalignment and dislocation. In polytraumatized patients, indication for primary surgery is given in complex spinal injuries with associated vascular, neurologic, or organ injuries as well as multilevel spinal fractures or unstable spinal injuries. In patients with unstable spinal injuries cardio-pulmonary instability and life threatening intracranial pressure are contra - indications for immediate spinal surgery. On the day of injury ventral spondylodesis of unstable cervical spine fractures of C3-C7 and dorsal spondylodesis of unstable thoraco-lumbar fractures using internal fixator are the standard procedures. Polytrauma patients benefit from early stabilization of spinal fractures including reduction of ventilation and ICU treatment, pneumonia rate, general complications, as well as hospital stay. However, it is controversial if mortality rate and neurologic outcome are affected by the time point of operative stabilization. PMID- 26814935 TI - Diagnosis, Timing and Treatment of Cervical Spine Injuries in Polytraumatized Patients. AB - Treatment of polytrauma patients has been discussed extensively during the past decades. Management in the prehospital phase, on admission, and in the early postoperative/ICU-period has to refer to injury severity, priority of injuries, and likelihood of development of multi organ failure. Cervical spine injuries are reported in 4-34% of polytrauma cases. Securing the cervical spine by a hard collar is one of the basic procedures in the prehospital phase. Different strategies of assessing the cervical spine are still discussed controversially. Since plain radiographs, CT-scan, MRI, and flexion/extension fluoroscopy still play a role in early diagnosis of cervical spine injury, we present an analysis of cervical spine injuries in our multiple trauma patients to elucidate our algorithm. We reviewed our data between January 2003 and December 2006 concerning epidemiology, diagnosis and treatment of cervical spine injury in polytrauma patients. Multislice-CT (MSCT) or Multidetector-CT was used as standard diagnostic procedures in the polytraumatized patient. In 97% of patients, CT scanning showed to be a reliable tool in detecting injuries of the cervical spine. Only in two patients (3%), additional MRI lead to a change in treatment strategy. Of 66 polytraumatized patients with significant cervical spine injury, 25 (37.9%) received surgical treatment within 24 h. Sixteen patients (24.2%) were treated surgically after stabilization on ICU. There was a better outcome concerning length of hospitalization in the "day-onesurgery" group. We consider MSCT as standard approach towards diagnosis of cervical spine injury in polytrauma patients. MRI and flexion/extension fluoroscopy can give additional information in selected cases. PMID- 26814936 TI - Primary Hemiarthroplasty for Proximal Humeral Fractures in the Elderly: Long-Term Functional Outcome and Social Implications. AB - BACKGROUND: Primary shoulder hemiarthroplasty is an established treatment modality for complex fractures of the proximal humerus. Long-term functional outcome is often disappointing. However, little is known about social implications particularly in the elderly. METHODS: A single-institution case series of consecutive geriatric patients (age > 70 years) treated with shoulder hemiarthroplasty for complex fractures of the proximal humerus between 1994 and 1997 was analysed. Postoperative morbidity, long-term function, radiological outcome and social implications were evaluated. RESULTS: Seventy-seven patients fulfilled the study criteria. Median age at the time of operation was 80 years (range 70-93 years). Systemic and local postoperative complications were observed in 8% including 2 patients (3%) with revision surgery. Postoperative mortality was 1%. Forty-eight patients (62%) were available for follow-up (median 49 months, range 25-80 months), 22 (29%) died from causes unrelated to hemiarthroplasty before follow-up and 7 patients (9%) did not attend follow-up examination. Median Constant-Murley score was 41 points (range 17-77 points). Long-term results concerning pain were satisfying. The Oxford shoulder score ranged from 14 to 40 (median 30). Forty-one patients (85%) still lived in their original environment and managed their daily life independently despite poor shoulder function. Four patients (8%) lived in a retirement home and 3 (6%) in a nursery home. Eighty percent of our patients were still able to use public transportation, do the daily shopping and wash their whole body by themselves. CONCLUSION: Most patients managed their daily life independently despite poor shoulder function. PMID- 26814937 TI - Functional Outcome after Operative Treatment of Displaced Fractures of the Acetabulum: A 12-month to 5-year Follow-up Investigation. AB - PURPOSE: To review our experience with 82 surgically treated displaced acetabular fractures over a 4-year period. PATIENTS AND METHODS: Ninety-three consecutive displaced acetabular fractures were consecutively operated on at Level I Trauma Center from January 1, 2000 through December 31, 2003, and 82 were available for review with a minimum of 12-month follow-up. Clinical (Merle D'Aubigne modified by Matta et al.) and radiographic (Matta) outcomes were evaluated. Complications and secondary operative procedures were documented. RESULTS: Anatomical reduction was achieved in 89% of the patients. At follow-up examination 12-60 months postoperatively (mean 32 months), clinical results were satisfactory in 65 patients (79.2% of the cases), with 14 excellent and 51 good results, and roentgenographic results were satisfactory in 70 patients (85.4% of the cases). Complications included a 12.2% incidence of sciatic nerve palsy (10 patients, two postoperative and eight posttraumatic), a 2.4% incidence of intraoperative vascular lesion (one external iliac artery and one external iliac vein), a 1.2% incidence of postoperative loss of reduction, a 1.2% incidence of infection, a 1.2% incidence of Brooker et al. class IV heterotopic ossification, a 2.4% incidence of posttraumatic osteoarthritis, and a 2.4% incidence of osteonecrosis of the femoral head. CONCLUSIONS: Operative treatment is an effective method for the management of displaced acetabular fractures. Clinical and roentgenographic results correlate closely with an anatomic reduction. Low complication rate can be expected if adequate preoperative assessment and planning is performed. Strategies to minimize the risk of thromboembolism and heterotopic ossification on the basis of mechanical pneumatic compression and antiinflammatory nonsteroidal drugs, respectively, are reliable techniques for these injuries. PMID- 26814938 TI - Cost-Effectiveness of Recombinant Activated Factor VII as Adjunctive Therapy for Bleeding Control in Severely Injured Trauma Patients in Germany. AB - PURPOSE: The purpose of this study was to assess the cost-effectiveness of recombinant activated factor VII (rFVIIa) as adjunctive therapy for the control of bleeding in patients with severe blunt trauma injuries in Germany. The primary outcome measure was incremental cost per quality-adjusted life-year (QALY) gained. MATERIALS AND METHODS: We developed a cost-effectiveness model based on patient-level data from a 30 day international, randomized, placebo-controlled phase II trial. The data were supplemented with secondary data from the German Trauma Register and German life tables to estimate lifetime costs and benefits. We assumed that the non-significant difference in mortality observed in the phase II trial of 5% in favor of rFVIIa could be verified in the ongoing, much larger follow-up trauma study. We adopted the perspective of third-party payers in Germany, and included all trauma-related healthcare costs. RESULTS: The incremental cost per QALY gained with rFVIIa relative to placebo was e29,451. The probability that this was below e30,000 and e40,000 was 51 and 58%, respectively. The estimates were sensitive to the differences observed in mortality and the applied discount rate. CONCLUSIONS: Based on preliminary evidence from a phase II trial, we conclude that, relative to placebo, rFVIIa may be a cost-effective therapy from the thirdparty payer perspective in Germany. PMID- 26814939 TI - The Volkmann Ischemic Contracture of the Forearm is Preventable. AB - The acute compartment syndrome of the forearm is rare and may therefore be easily missed. Although many clinicians will not see such a patient during their entire career, profound knowledge of the symptoms is required to recognize the syndrome in time. Besides immediate identification of the compartment syndrome early surgical treatment is mandatory to avoid its devastating consequences. Then the functional results can be good, but if the correct diagnosis is missed a Volkmann's ischemic contracture will invariably develop. This paper aims to attend the reader to this diagnostic pitfall. Two patients with a compartment syndrome of the forearm are described to illustrate both ends of this diagnostic challenge. Pathophysiological, anatomical and clinical aspects, classification and therapeutic modalities are reviewed. PMID- 26814940 TI - Isolated Gallbladder Injury after Blunt Abdominal Trauma: a Case Report and Review. AB - We describe a case of isolated gallbladder contusion after deceleration trauma. On admission, no evident signs of intra-abdominal injury were present. However, after 24 h observation an explorative laparotomy was performed because of persistent abdominal complaints. A contusion of the gallbladder wall was found with intraluminal haematoma and a cholecystectomy was performed. Isolated injury of the gallbladder after blunt trauma is extremely rare. Risk factors are distention of the gallbladder, deceleration trauma and the presence of a relatively mobile gallbladder. Clinical signs often are very subtle. Delayed presentation is common with signs of hemobilia or obstruction due to intraluminal clots. Ultrasound and computed tomography are suitable diagnostic tools. However, the diagnosis is often missed if no other injuries are present. Signs pointing to gallbladder injury are a collapsed gallbladder with pericholecystic fluid or a hydroptic gallbladder with intraluminal hematoma. Hepatobiliary scintigraphy or angiography might be necessary if additional injuries are suspected. The choice of treatment depends on the kind of injury. Contusion of the gallbladder allows conservative treatment, but in case of a rupture, surgery will be necessary. Accompanying bile duct injuries can be treated by endoscopic stenting. If active arterial bleeding is present, selective embolization can be performed. PMID- 26814941 TI - Traumatic Injury of the Superior Mesenteric Vein: Ligate, Repair or Shunt? AB - We report a case of SMV injury in a critically ill patient. The patient was a 19 year-old woman involved in a motor vehicle collision. Her injuries included grade II splenic and renal lacerations, devascularized and lacerated right and transverse colon, a transected transverse mesocolon, a massive shear injury of her abdominal wall, and two partial SMV transections. At initial damage control laparotomy, the SMV was ligated, the devascularized bowel resected and a temporary abdominal closure applied. At re-operation, a mesocaval shunt using saphenous vein was employed. The shunt failed and the patient required a saphenous vein jump graft. Although visceral vascular injuries are rare, ligation of the SMV in a damage control situation is acceptable. This case study is the first to discuss appropriate treatment when interruption to a patient's collateral visceral venous drainage limits the surgeon's ability to ligate. In these situations, bypass shunts may be successful. PMID- 26814942 TI - Complete Avulsion of the Pectoralis Major Tendon: a Case Report. AB - Rupture of the pectoralis major muscle is a rare injury, usually occurring during sports activities or after direct trauma. This article describes the clinical presentation, diagnostic tools and treatment of a patient with a complete avulsion of the pectoralis major tendon. PMID- 26814943 TI - The Clavicular Hook Plate: Consequences in Three Cases. AB - The small fragment AO clavicular hook plate is indicated for certain fractures of the lateral end of clavicle and for symptomatic acromio-clavicular joint dislocations where there is rupture of the stabilizing ligaments. The complex anatomy and biomechanics of the acromio-clavicular joint can lead to complications that result in damage to the joint itself or acromial erosion. In addition, the rotator cuff complex is at risk of injury when inserting the plate. We report three cases where patients who underwent hook plate fixation subsequently required removal of the implant due to complications previously unreported in current literature. PMID- 26814944 TI - Intramedullary Stabilization of Periprosthetic Fractures of the Femur Taking Special Account of Bone Defects. AB - OBJECTIVE: Healing of the periprosthetic fracture and area of defective bone by the bone healing mechanisms of intramedullary stabilization. Reconstruction of the correct length, axial alignment, and rotation of the fractured femoral shaft by anchoring a revision stem in the intact femoral diaphysis. INDICATIONS: Periprosthetic femoral shaft fracture in the region of the prosthetic stem combined with preexistent loosening and/or defect in the periprosthetic bone bed (Vancouver classification type B2 and B3). CONTRAINDICATIONS: General contraindications, local infection. SURGICAL TECHNIQUE: Lateral transmuscular approach to the femoral shaft. Longitudinal osteotomy of the proximal femur taking the geometry of the fracture into account. Opening of an anterior "bone shell". Removal of the loose prosthetic stem and cement. Debridement. Preparation of the femoral diaphysis and insertion of a distally anchored revision stem. Distal locking. Repositioning of the "bone shell", reduction of the fracture, and retention with cerclage wires. POSTOPERATIVE MANAGEMENT: Bed rest for approximately 1 week, mobilization with 20 kg partial weight bearing for 12 weeks, gradual increase in weight bearing with radiologic checks on progress, removal of the distal locking bolts after 12-24 months at the earliest. RESULTS: 21 patients (13 women, eight men) aged between 43 and 86 years (mean age: 71.2 years) with periprosthetic fracture of the femur, additional loosening of the stem in eight cases (Vancouver B2) and additional bone loss in 13 cases (Vancouver B3). Postoperative complications: two fractures following another fall (repeat operations: one replacement, one plate), four revisions due to subsidence of the stem (three replacements involving change to a standard stem with healed proximal femur, one replacement with another interlocked revision stem). Bone healing occurred for all fractures after a mean 5.6 months (3-11 months). Follow- up examination after a mean 4.5 years: all patients were able to walk, average Harris Score 70.5 points (29- 95 points). PMID- 26814945 TI - Direct Transformation of Ethylarenes into Primary Aromatic Amides with N Bromosuccinimide and I2-Aqueous NH3. AB - A variety of ethylarenes were converted into the corresponding primary aromatic amides in good yields via treatment with N-bromosuccinimide in the presence of a catalytic amount of 2,2'-azobis(isobutyronitrile) in a mixture of ethyl acetate and water, acetonitrile and water, or chloroform and water, followed by reaction with molecular iodine and aq NH3 in one pot. It was found that aryl alpha bromomethyl ketones and/or aryl methyl ketones were formed at the first reaction step and their iodoform-type reaction occurred at the second reaction step to provide primary aromatic amides. The present reaction is a useful and practical transition-metal-free method for the preparation of primary aromatic amides from ethylarenes. PMID- 26814946 TI - In-Hospital Outcome of Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction: Results from Royal Hospital Percutaneous Coronary Intervention Registry, Oman. AB - OBJECTIVES: Cardiogenic shock (CS) is still the leading cause of in-hospital mortality in patients presenting with acute myocardial infarction (AMI). The aim of this study was to determine the in-hospital mortality and clinical outcome in AMI patients presenting with CS in a tertiary hospital in Oman. METHODS: This retrospective observational study included patients admitted to the cardiology department between January 2013 and December 2014. A purposive sampling technique was used, and 63 AMI patients with CS admitted to (36.5%) or transferred from a regional hospital (63.5%) were selected for the study. RESULTS: Of 63 patients, 73% (n = 46) were Omani and 27% (n = 17) were expatriates: 79% were male and 21% were female. The mean age of patients was 60+/-12 years. The highest incidence of CS (30%) was observed in the 51-60 year age group. Diabetes mellitus (43%) and hypertension (40%) were the predominant risk factors. Ninety-two percent of patients had ST-elevation MI, 58.7% patients were thrombolysed, and 8% had non-ST elevation MI. Three-quarters (75%) of CS patients had severe left ventricular systolic dysfunction (defined as ejection fraction <30%). Coronary angiogram showed single vessel disease in 17%, double vessel disease in 40%, and triple vessel disease in 32% and left main disease in 11%. The majority of the patients (93.6%) underwent percutaneous coronary intervention (PCI), among them 23 (36.5%) underwent primary PCI. In-hospital mortality was 52.4% in this study. CONCLUSIONS: CS in AMI patients presenting to a tertiary hospital in Oman have high in-hospital mortality despite the majority undergoing PCI. Even though the in-hospital mortality is comparable to other studies and registries, there is an urgent need to determine the causes and find any remedies to provide better care for such patients, specifically concentrating on the early transfer of patients from regional hospitals for early PCI. PMID- 26814947 TI - Focus on spinal navigation. PMID- 26814948 TI - O-arm((r))-based spinal navigation and intraoperative 3D-imaging: first experiences. AB - Since the first use of instrument-tracking techniques in the early 1990s, image guided technologies became a leading topic in all branches of spine surgery. Today, navigation is a widely available tool in spine surgery and has become a part of clinical routine in many centers for a large variety of indications. Spinal navigation may not only contribute to more precision during surgery, but it may also reduce radiation exposure and fluoroscopy time, with advantages not only for the patient but also for the operating room personnel. Different registration algorithms have been developed differing in terms of the type of image data used by the navigation system (preoperatively acquired computed tomography [CT] images, intraoperatively acquired fluoroscopy images) and the way virtual and physical reality is matched. There is a tendency toward a higher accuracy for 3D fluoroscopy-based registration algorithms. The O-arm((r)) represents a new flat-panel technology with the source and detector moving in a 360 degrees arc around the patient. In combination with the Stealth((r)) station system, navigation may start immediately after automated registration with already referenced instruments. After instrumentation, an additional scan may confirm intraoperatively the correct positioning of the instrumentation. The first experiences with the system are described in this paper. PMID- 26814949 TI - 3D-based navigation in posterior stabilisations of the cervical and thoracic spine: problems and benefits. Results of 451 screws. AB - INTRODUCTION: Navigated procedures in spinal surgery have been established due to an increasing demand for precision. Especially, 3D C-arms connected to navigation systems are being used more often and can be utilised intraoperatively for the planning and controlling of screw positions. This prospective study analyses our experiences with 3D-based navigation in posterior stabilisations in the cervical and thoracic spine. METHODS: A 3D C-Arm (Ziehm Vision Vario 3D((r))) was connected to a navigation system (VectorVision, Brainlab((r))) and used for the placement of, in total, 451 screws among 67 patients. Of those, 14 patients had to undergo operations in the cervical and 53 in the thoracic spine. Postoperatively, the positioning was observed with computed tomography (CT). RESULTS: The application time is approximately 6 min. In total, 354/451 (78.5%) screws could be inserted assisted with navigation, and 272/451 (60.3%) were controlled intraoperatively. Regarding the cervical spine, in 87.1% (61/70) of the screws, the navigation procedure was uneventful. The positioning of 63.2% (43/68) of the screws was checked intraoperatively. In the upper thoracic spine, 77% (293/381) could be placed with navigation and 59.6% (227/381) were controlled intraoperatively. Occasionally, the scanning setup was problematic. Correct placement was seen in 92.7% of screws; for the remaining screws, no revision was needed. CONCLUSIONS: Intraoperative 3D imaging navigation for posterior spinal stabilisations is technically feasible and reliable in clinical use. The image quality depends on the individual bone density. With undisturbed visibility of the vertebral body, the reliability of 3D-based navigation is comparable to that of CT-based procedures. Additionally, it has the advantage of skipping the preoperative acquisition of data as well as the matching process, with reduced radiation doses. PMID- 26814951 TI - Anterior column reconstruction in thoracolumbar injuries utilizing a computer assisted navigation system. AB - BACKGROUND: Discectomy, corpectomy, and resection of isolated posterior wall fragments are technically demanding steps requiring maximum surgical precision during anterior reconstruction of the unstable thoracolumbar spine. PURPOSE: This study investigates the feasibility of computer-aided guidance for these steps. It also analyzes the precision, advantages, and disadvantages of the procedure. STUDY DESIGN: Controlled clinical trial. PATIENT SAMPLE: 21 patients were included in the trial group; the control group consisted of 10 patients. OUTCOME MEASURES: Total time for surgery was noted. To assess surgical precision, decentralization of the cage was measured in postoperative X-rays. Additionally, parallel alignment of vertebral body endplates with the cage was evaluated in postoperative CT scans. METHODS: Vertebral body fractures of the thoracolumbar spine addressed by disc-/corpectomy and subsequent cage interposition for anterior reconstruction were included. All surgical steps were performed under endoscopic assistance. In the trial group, disc- and corpectomy were performed under computer-aided guidance; in the control group, no computer navigation was utilized. In cases of initial neurological deficit after trauma, the patients underwent emergency laminectomy during the initial posterior stabilization procedure. During the second-stage anterior procedure, resection of the posterior wall fragment with the aid of computer-aided navigation was performed. RESULTS: Fractures were localized between Th9 and L1 in the trial group, and Th10 and L1 in the control group. Time for surgery was significantly shorter in the control group: 1.7 h +/- 0.5, as opposed to 3.8 h +/- 1.0 in the trial group (p < 0.0005). In contrast, data on surgical precision did not show statistically significant differences between both groups for either decentralization or parallel endplate alignment of cages. Remarkably, we noted two cases of subsidence in bilevel cages in the control group, whereas this was only noted in one case in the trial group. However, this difference was not statistically significant. There were five patients with initial neurological deficits. At the time of follow-up, the neurological statuses of all five had improved by at least one Frankel grade. CONCLUSIONS: Computer-aided guidance in anterior reconstruction of the thoracolumbar spine is a technically feasible option that may aid in the performance of disc- and corpectomy, as well as the resection of isolated posterior wall fragments in cases with initial neurological compromise. However, total time for surgery is significantly prolongated by this technique. There were no differences in the precision of cage positioning between groups. However, during discectomy, the use of computer navigation may aid in the protection of adjacent endplates, as there was a trend towards fewer cases with cage subsidence in the navigated group. PMID- 26814950 TI - Accuracy of CT-assisted pedicle screw placement after CT-controlled, presurgical guide wire implantation in traumatic and pathological fractures in the thoracic spine. AB - INTRODUCTION: The aim of this study was to evaluate the accuracy of pedicle screw placement after computed tomography (CT)-assisted positioning of guide wires and subsequent insertion of transpedicular screws in particularly narrow pedicles in the thoracic spine. Transpedicular pedicle screw placement has been commonly used for a number of decades. However, a significant number of malpositioned screws still occur, especially in the thoracic spine, potentially correlating with relevant complications, e.g., neurological deterioration. PATIENTS AND METHODS: A retrospective analysis was performed after CT-assisted and -controlled implantation of guide wires into the pedicle. A total of 39 patients underwent dorsal spondylodesis using two different internal fixation systems, i.e., with a cannulated or a solid screw design. The postoperative screw position was evaluated with CT scans in three planes in a total of 254 screws. RESULTS: The number of the screws inserted at each level were as follows (total n = 326): T1, n = 8; T2, n = 26; T3, n = 26; T4, n = 36; T5, n = 50; T6, n = 37; T7, n = 38; T8, n = 32; T9, n = 24; T10, n = 18; T11, n = 10; T12, n = 6. Indications for the operative treatment were fractures, tumors, and infectious diseases. A total of 254 screws inserted were evaluated by CT scan in order to determine the screw position inside the pedicle and potential perforation of the pedicle wall. The overall rate of pedicle wall perforation was 7.5%, including 1.2% perforations of the medial wall. A significant correlation between the perforation rate and the type of fixation system in favor of the cannulated system was found (P = 0.033). During the study, no revision surgery due to screw misplacement was necessary. None of the treated patients showed neurological deterioration after screw implantation during the presented study. CONCLUSION: The CT-assisted pedicle screw implantation procedure using guide wires implanted prior to surgery is an accurate, reliable, and safe method for dorsal spondylodesis in the treatment of a variety of spinal instabilities, including fractures, tumors, and infections. PMID- 26814952 TI - Prevalence of ocular and orbital injuries in polytrauma patients. AB - INTRODUCTION: Polytrauma patients usually suffer from both life-threatening injuries, where early intervention is mandatory in order to prevent mortality from uncontrollable haemorrhage-especially during the "golden hour", and secondary injuries of lower priority which receive delayed referral or treatment. Non-life-threatening injuries can sometimes be overlooked and so remain untreated until a much later stage. The aim of this study was to investigate the incidence of eye (ocular and orbital) injuries in polytrauma (injury severity score >15) patients and describe their complexities and outcomes. MATERIALS AND METHODS: Over a 10-year period (1991-2001), all polytrauma patients admitted in our institution were evaluated. Patients with ocular and orbital injuries were identified and their records were retrospectively analyzed. RESULTS: Out of a total of 2,985 polytrauma patients, 222 (7.5%) met the inclusion criteria. Forty one case notes were not retraceable. The files of 181 patients were therefore available for review. The mean age of this group of patients was 33 years (3-84) with a sex ratio (male: female ratio) 5:1. The types of eye injuries encountered were orbital wall fractures (61%), periorbital swelling or hematoma (46%), sub conjunctival hemorrhage (23%), periorbital lacerations (22%), optic nerve trauma (11%) and penetrating eye injuries (6%). Visual impairment resulted in about 67% of survivors, including loss of eye in 24%. Diplopia requiring intervention was seen in 24% of the cases. CONCLUSIONS: Polytrauma patients are at high risk for vision-threatening injuries, and an early multidisciplinary approach is essential for early detection and treatment. PMID- 26814953 TI - Fournier's gangrene: analysis of prognostic variables in 34 patients. AB - INTRODUCTION: Fournier's gangrene (FG) is the necrotizing fasciitis of the perineum and genital area. The objective of this study was to assess risk factors for mortality. MATERIALS AND METHODS: We conducted an analytic and retrospective study of the patients with FG treated at our institution between 1998 and 2008. Statistical analysis was performed with the Statistical Package for Social Science for Windows, version 15.0, using the Mann-Whitney test for quantitative variables, and the chi-square and Fisher exact tests for qualitative variables, in univariate analyses. RESULTS: Of the 34 patients treated, 25 survived (74%) and 9 died (26%) with a median timing of 29 days (13, 60). Statistically significant differences were not found in age, sex and predisposing factors, except heart disease (p = 0.034). Admission laboratory parameters and severity criteria showed significant differences in serum urea (p = 0.007), potassium (p = 0.008), alkaline phosphatase (p = 0.014) and Fournier's gangrene severity index score (FGSIS) (p = 0.008). Others factors such as duration of symptoms before hospital admission, extent of body surface area, number of surgical debridements, additional surgical manoeuvers (supra-pubic catheterization or colostomy), microbiological cultures and ICU stay did not show significant differences. CONCLUSIONS: FG is a life-threatening necrotizing fasciitis with a high mortality rate. In our study, prognostic variables were heart disease, admission serum urea, potassium, alkaline phosphatase, and FGSIS. More studies are needed to validate these findings. PMID- 26814954 TI - Small bowel obstruction: early parameters predicting the need for surgical intervention. AB - AIM: To study and identify early clinical and radiological findings that could help to predict operative intervention for small bowel obstruction. MATERIALS AND METHODS: One hundred and nine consecutive patients with small bowel obstruction who underwent small bowel follow-through examination with Gastrografin((r)) during 2005-2006. The patients were divided into an operative group and a non operative group, n = 44 and 65, respectively. Findings primarily noted were those which were possible to register within 1-4 h from hospital arrival. RESULTS: In univariate analyses, factors found to be significantly associated with surgical intervention were no prior abdominal surgery, the presence of radiological differential air fluid levels, and absence of flatulence 24 h prior to admission, CRP > 10 mg/L and dehydration at admission. In multivariate analyses, the presence of dehydration and radiological differentiated air fluid levels were independent predictive factors of significance. Absence of all factors significantly favored non-operative treatment, while operative treatment was significantly favored when two or more factors were present. CONCLUSIONS: The presence of two or more early predictive factors as defined above, available at admission, significantly correlates with a likelihood of complete obstruction and the need of surgical intervention. PMID- 26814955 TI - The association between depressive mood and pain amongst individuals with limb amputations. AB - INTRODUCTION: The purpose of this study was to evaluate the relationship between pain and depressive mood amongst persons with limb amputations, and to examine the relationship between the etiology (work-related trauma or other types) and depressive mood. METHODS: Mailed questionnaires were used to collect personal information from 69 limb amputees living in the community. The severity of limb amputation-related pain was rated using the Chronic Pain Grade scale. Eighteen (26.1%) of the participants referred their pain as Grade 0 (no pain) and 25 (36.2%) referred as Grade I (mild pain). Depressive mood was classified using the Zung Self-Rating Depression Scale. RESULTS: Eighteen (26.1%) of the participants were classified as having mild depression, 16 (23.2%) as having moderate depression, and 7 (10.1%) as having severe depressive mood. A significant proportion of participants with moderate or severe depression were amputees with work-related etiology for their loss of limbs. In addition, amputees with more severe depressive mood tended to experience a higher level of amputation-related pain than amputees with less severe depressive mood. CONCLUSIONS: The results of this study revealed the validity of optional approaches such as prescription of antidepressants or psychological counseling to improve mental health of individuals with limb amputations. PMID- 26814956 TI - Doppler ultrasound for the assessment of conservatively treated blunt splenic injuries: a prospective study. AB - INTRODUCTION: The type and need for follow-up of non-operatively managed blunt splenic injuries remain controversial. The use of Doppler ultrasound to identify post-traumatic splenic pseudoaneurysms, considered to be the main cause of "delayed" splenic rupture, has not been well described. PATIENTS AND METHODS: A 5 year prospective study was performed from 2004 to 2008. All patients with blunt splenic injury diagnosed with computerized tomography, who were treated non operatively, were included in the study. Doppler ultrasound examination was performed 24-48 h post-injury. Consecutive Doppler ultrasound examinations were done on 7, 14 and 21 days post-injury for patients diagnosed with a splenic pseudoaneurysm. Demographic and clinical data were collected. Ambulatory follow up continued for 4 weeks after hospital discharge. RESULTS: A total of 38 patients were enrolled in the study. Grading of splenic injury demonstrated 19 (50%) patients with Grade I, 16 (42%) with Grade II and 3 (8%) with Grade III injuries. Two patients (5%) had pseudoaneurysms. All pseudoaneurysms underwent complete resolution within 2 weeks after diagnosis. No patients received blood products, or had angio-embolization or surgery during the study period. All patients were found to be asymptomatic and stable at the 4-week follow-up. CONCLUSIONS: Doppler ultrasound can be an effective and a safe noninvasive modality for evaluation and follow-up of patients with blunt splenic injury. The utility and cost-effectiveness of routine surveillance requires further study. PMID- 26814957 TI - Teaching in daily clinical practice: a necessary evil or an opportunity? Doctors as teachers. AB - Teaching is an important part of our medical role as physicians. Though all doctors are usually well prepared for their clinical roles, few are trained to teach. It can be demonstrated that improved teaching performance leads to better learning outcomes for students and doctors. However, clinical teaching faces many challenges and problems. The series "Teaching in daily clinical practice," which commences with this article, will describe basic educational principles that are applicable in all phases of the learning and teaching of students, junior doctors and speciality trainees. PMID- 26814960 TI - Alcohol abuse after traumatic brain injury: Experimental and clinical evidence. AB - Brain injury survivors, particularly those injured early in life are very likely to abuse drugs and alcohol later in life. Alcohol abuse following traumatic brain injury (TBI) is associated with poorer rehabilitation outcomes and a greatly increased chance of suffering future head trauma. Thus, substance abuse among persons with brain injury reduces the chances for positive long-term outcomes and greatly increases the societal costs. In this review, we discuss the evidence for modulation of drinking behavior after TBI and the costs of problem drinking after TBI from both a biomedical and economic perspective. Further, we review the existing animal models of drinking after brain injury and consider the potential underlying psychosocial and neurobiological mediators of this phenomenon. In particular, we highlight the potential interactions among TBI, neuroinflammation and alcohol abuse. Substance abuse is a major problem in this vulnerable patient population and a greater understanding of the underlying biology has the potential to greatly improve outcomes. PMID- 26814959 TI - Can the Direct Medical Cost of Chronic Disease Be Transferred across Different Countries? Using Cost-of-Illness Studies on Type 2 Diabetes, Epilepsy and Schizophrenia as Examples. AB - OBJECTIVES: To systematically review cost of illness studies for schizophrenia (SC), epilepsy (EP) and type 2 diabetes mellitus (T2DM) and explore the transferability of direct medical cost across countries. METHODS: A comprehensive literature search was performed to yield studies that estimated direct medical costs. A generalized linear model (GLM) with gamma distribution and log link was utilized to explore the variation in costs that accounted by the included factors. Both parametric (Random-effects model) and non-parametric (Boot strapping) meta-analyses were performed to pool the converted raw cost data (expressed as percentage of GDP/capita of the country where the study was conducted). RESULTS: In total, 93 articles were included (40 studies were for T2DM, 34 studies for EP and 19 studies for SC). Significant variances were detected inter- and intra-disease classes for the direct medical costs. Multivariate analysis identified that GDP/capita (p<0.05) was a significant factor contributing to the large variance in the cost results. Bootstrapping meta analysis generated more conservative estimations with slightly wider 95% confidence intervals (CI) than the parametric meta-analysis, yielding a mean (95%CI) of 16.43% (11.32, 21.54) for T2DM, 36.17% (22.34, 50.00) for SC and 10.49% (7.86, 13.41) for EP. CONCLUSIONS: Converting the raw cost data into percentage of GDP/capita of individual country was demonstrated to be a feasible approach to transfer the direct medical cost across countries. The approach from our study to obtain an estimated direct cost value along with the size of specific disease population from each jurisdiction could be used for a quick check on the economic burden of particular disease for countries without such data. PMID- 26814961 TI - Role of GABA(B) receptors in learning and memory and neurological disorders. AB - Although it is evident from the literature that altered GABAB receptor function does affect behavior, these results often do not correspond well. These differences could be due to the task protocol, animal strain, ligand concentration, or timing of administration utilized. Because several clinical populations exhibit learning and memory deficits in addition to altered markers of GABA and the GABAB receptor, it is important to determine whether altered GABAB receptor function is capable of contributing to the deficits. The aim of this review is to examine the effect of altered GABAB receptor function on synaptic plasticity as demonstrated by in vitro data, as well as the effects on performance in learning and memory tasks. Finally, data regarding altered GABA and GABAB receptor markers within clinical populations will be reviewed. Together, the data agree that proper functioning of GABAB receptors is crucial for numerous learning and memory tasks and that targeting this system via pharmaceuticals may benefit several clinical populations. PMID- 26814963 TI - Schizophrenia risk from complex variation of complement component 4. AB - Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia. PMID- 26814965 TI - The temporal scaling of Caenorhabditis elegans ageing. AB - The process of ageing makes death increasingly likely, involving a random aspect that produces a wide distribution of lifespan even in homogeneous populations. The study of this stochastic behaviour may link molecular mechanisms to the ageing process that determines lifespan. Here, by collecting high-precision mortality statistics from large populations, we observe that interventions as diverse as changes in diet, temperature, exposure to oxidative stress, and disruption of genes including the heat shock factor hsf-1, the hypoxia-inducible factor hif-1, and the insulin/IGF-1 pathway components daf-2, age-1, and daf-16 all alter lifespan distributions by an apparent stretching or shrinking of time. To produce such temporal scaling, each intervention must alter to the same extent throughout adult life all physiological determinants of the risk of death. Organismic ageing in Caenorhabditis elegans therefore appears to involve aspects of physiology that respond in concert to a diverse set of interventions. In this way, temporal scaling identifies a novel state variable, r(t), that governs the risk of death and whose average decay dynamics involves a single effective rate constant of ageing, kr. Interventions that produce temporal scaling influence lifespan exclusively by altering kr. Such interventions, when applied transiently even in early adulthood, temporarily alter kr with an attendant transient increase or decrease in the rate of change in r and a permanent effect on remaining lifespan. The existence of an organismal ageing dynamics that is invariant across genetic and environmental contexts provides the basis for a new, quantitative framework for evaluating the manner and extent to which specific molecular processes contribute to the aspect of ageing that determines lifespan. PMID- 26814966 TI - Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells. AB - ATP-dependent chromatin remodellers allow access to DNA for transcription factors and the general transcription machinery, but whether mammalian chromatin remodellers target specific nucleosomes to regulate transcription is unclear. Here we present genome-wide remodeller-nucleosome interaction profiles for the chromatin remodellers Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind one or both full nucleosomes that flank micrococcal nuclease (MNase)-defined nucleosome-free promoter regions (NFRs), where they separate divergent transcription. Surprisingly, large CpG-rich NFRs that extend downstream of annotated transcriptional start sites are nevertheless bound by non-nucleosomal or subnucleosomal histone variants (H3.3 and H2A.Z) and marked by H3K4me3 and H3K27ac modifications. RNA polymerase II therefore navigates hundreds of base pairs of altered chromatin in the sense direction before encountering an MNase-resistant nucleosome at the 3' end of the NFR. Transcriptome analysis after remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. Whereas at active genes individual remodellers have either positive or negative roles via altering nucleosome stability, at polycomb-enriched bivalent genes the same remodellers act in an opposite manner. These findings indicate that remodellers target specific nucleosomes at the edge of NFRs, where they regulate ES cell transcriptional programs. PMID- 26814967 TI - Active medulloblastoma enhancers reveal subgroup-specific cellular origins. AB - Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is lacking. Here, using H3K27ac and BRD4 chromatin immunoprecipitation followed by sequencing (ChIP-seq) coupled with tissue-matched DNA methylation and transcriptome data, we describe the active cis-regulatory landscape across 28 primary medulloblastoma specimens. Analysis of differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity and revealed novel, clinically relevant insights into medulloblastoma biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors, validated by ChIP-seq, that is responsible for subgroup divergence, and implicates candidate cells of origin for Group 4. Our integrated analysis of enhancer elements in a large series of primary tumour samples reveals insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins. PMID- 26814969 TI - Corrigendum: Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis. PMID- 26814968 TI - An essential receptor for adeno-associated virus infection. AB - Adeno-associated virus (AAV) vectors are currently the leading candidates for virus-based gene therapies because of their broad tissue tropism, non-pathogenic nature and low immunogenicity. They have been successfully used in clinical trials to treat hereditary diseases such as haemophilia B (ref. 2), and have been approved for treatment of lipoprotein lipase deficiency in Europe. Considerable efforts have been made to engineer AAV variants with novel and biomedically valuable cell tropisms to allow efficacious systemic administration, yet basic aspects of AAV cellular entry are still poorly understood. In particular, the protein receptor(s) required for AAV entry after cell attachment remains unknown. Here we use an unbiased genetic screen to identify proteins essential for AAV serotype 2 (AAV2) infection in a haploid human cell line. The most significantly enriched gene of the screen encodes a previously uncharacterized type I transmembrane protein, KIAA0319L (denoted hereafter as AAV receptor (AAVR)). We characterize AAVR as a protein capable of rapid endocytosis from the plasma membrane and trafficking to the trans-Golgi network. We show that AAVR directly binds to AAV2 particles, and that anti-AAVR antibodies efficiently block AAV2 infection. Moreover, genetic ablation of AAVR renders a wide range of mammalian cell types highly resistant to AAV2 infection. Notably, AAVR serves as a critical host factor for all tested AAV serotypes. The importance of AAVR for in vivo gene delivery is further highlighted by the robust resistance of Aavr(-/-) (also known as Au040320(-/-) and Kiaa0319l(-/-)) mice to AAV infection. Collectively, our data indicate that AAVR is a universal receptor involved in AAV infection. PMID- 26814962 TI - Persistent HIV-1 replication maintains the tissue reservoir during therapy. AB - Lymphoid tissue is a key reservoir established by HIV-1 during acute infection. It is a site associated with viral production, storage of viral particles in immune complexes, and viral persistence. Although combinations of antiretroviral drugs usually suppress viral replication and reduce viral RNA to undetectable levels in blood, it is unclear whether treatment fully suppresses viral replication in lymphoid tissue reservoirs. Here we show that virus evolution and trafficking between tissue compartments continues in patients with undetectable levels of virus in their bloodstream. We present a spatial and dynamic model of persistent viral replication and spread that indicates why the development of drug resistance is not a foregone conclusion under conditions in which drug concentrations are insufficient to completely block virus replication. These data provide new insights into the evolutionary and infection dynamics of the virus population within the host, revealing that HIV-1 can continue to replicate and replenish the viral reservoir despite potent antiretroviral therapy. PMID- 26814971 TI - Observation of polar vortices in oxide superlattices. AB - The complex interplay of spin, charge, orbital and lattice degrees of freedom provides a plethora of exotic phases and physical phenomena. In recent years, complex spin topologies have emerged as a consequence of the electronic band structure and the interplay between spin and spin-orbit coupling in materials. Here we produce complex topologies of electrical polarization--namely, nanometre scale vortex-antivortex (that is, clockwise-anticlockwise) arrays that are reminiscent of rotational spin topologies--by making use of the competition between charge, orbital and lattice degrees of freedom in superlattices of alternating lead titanate and strontium titanate layers. Atomic-scale mapping of the polar atomic displacements by scanning transmission electron microscopy reveals the presence of long-range ordered vortex-antivortex arrays that exhibit nearly continuous polarization rotation. Phase-field modelling confirms that the vortex array is the low-energy state for a range of superlattice periods. Within this range, the large gradient energy from the vortex structure is counterbalanced by the corresponding large reduction in overall electrostatic energy (which would otherwise arise from polar discontinuities at the lead titanate/strontium titanate interfaces) and the elastic energy associated with epitaxial constraints and domain formation. These observations have implications for the creation of new states of matter (such as dipolar skyrmions, hedgehog states) and associated phenomena in ferroic materials, such as electrically controllable chirality. PMID- 26814970 TI - NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux. AB - Inflammasomes are intracellular protein complexes that drive the activation of inflammatory caspases. So far, four inflammasomes involving NLRP1, NLRP3, NLRC4 and AIM2 have been described that recruit the common adaptor protein ASC to activate caspase-1, leading to the secretion of mature IL-1beta and IL-18 proteins. The NLRP3 inflammasome has been implicated in the pathogenesis of several acquired inflammatory diseases as well as cryopyrin-associated periodic fever syndromes (CAPS) caused by inherited NLRP3 mutations. Potassium efflux is a common step that is essential for NLRP3 inflammasome activation induced by many stimuli. Despite extensive investigation, the molecular mechanism leading to NLRP3 activation in response to potassium efflux remains unknown. Here we report the identification of NEK7, a member of the family of mammalian NIMA-related kinases (NEK proteins), as an NLRP3-binding protein that acts downstream of potassium efflux to regulate NLRP3 oligomerization and activation. In the absence of NEK7, caspase-1 activation and IL-1beta release were abrogated in response to signals that activate NLRP3, but not NLRC4 or AIM2 inflammasomes. NLRP3 activating stimuli promoted the NLRP3-NEK7 interaction in a process that was dependent on potassium efflux. NLRP3 associated with the catalytic domain of NEK7, but the catalytic activity of NEK7 was shown to be dispensable for activation of the NLRP3 inflammasome. Activated macrophages formed a high molecular-mass NLRP3-NEK7 complex, which, along with ASC oligomerization and ASC speck formation, was abrogated in the absence of NEK7. NEK7 was required for macrophages containing the CAPS-associated NLRP3(R258W) activating mutation to activate caspase-1. Mouse chimaeras reconstituted with wild-type, Nek7(-/-) or Nlrp3(-/-) haematopoietic cells showed that NEK7 was required for NLRP3 inflammasome activation in vivo. These studies demonstrate that NEK7 is an essential protein that acts downstream of potassium efflux to mediate NLRP3 inflammasome assembly and activation. PMID- 26814972 TI - Schizophrenia: From genetics to physiology at last. PMID- 26814973 TI - Genomics: From sea to sea. PMID- 26814974 TI - Ageing: A stretch in time. PMID- 26814975 TI - [Mechanisms of Resistance in Antihormone Therapies of Advanced Prostate Cancer]. AB - With the development of Abiraterone and Enzalutamide new treatment option have become available in addition to Docetaxel for first-line treatment of castration resistant prostate cancer. However, resistance and ultimately failure occurs inevitably with all available treatment options. Moreover, cross-resistance leads to considerably reduced efficacy in second-line treatment. Preclinical data suggest discriminative mechanisms of resistance development for Abiraterone and Enzalutamide. Clinical confirmation of these putative mechanisms for treatment failure might facilitate recommendations for future sequencing of these drugs. PMID- 26814976 TI - Pathway engineering of Propionibacterium jensenii for improved production of propionic acid. AB - Propionic acid (PA) is an important chemical building block widely used in the food, pharmaceutical, and chemical industries. In our previous study, a shuttle vector was developed as a useful tool for engineering Propionibacterium jensenii, and two key enzymes-glycerol dehydrogenase and malate dehydrogenase-were overexpressed to improve PA titer. Here, we aimed to improve PA production further via the pathway engineering of P. jensenii. First, the phosphoenolpyruvate carboxylase gene (ppc) from Klebsiella pneumoniae was overexpressed to access the one-step synthesis of oxaloacetate directly from phosphoenolpyruvate without pyruvate as intermediate. Next, genes encoding lactate dehydrogenase (ldh) and pyruvate oxidase (poxB) were deleted to block the synthesis of the by-products lactic acid and acetic acid, respectively. Overexpression of ppc and deleting ldh improved PA titer from 26.95 +/- 1.21 g.L( 1) to 33.21 +/- 1.92 g.L(-1) and 30.50 +/- 1.63 g.L(-1), whereas poxB deletion decreased it. The influence of this pathway engineering on gene transcription, enzyme expression, NADH/NAD(+) ratio, and metabolite concentration was also investigated. Finally, PA production in P. jensenii with ppc overexpression as well as ldh deletion was investigated, which resulted in further increases in PA titer to 34.93 +/- 2.99 g.L(-1) in a fed-batch culture. PMID- 26814977 TI - Survey of Philippine coffee beans for the presence of ochratoxigenic fungi. AB - In 2012 to 2014, Philippine green coffee beans from Coffea arabica in Benguet and Ifugao; Coffea canephora var. Robusta in Abra, Cavite, and Ifugao; and Coffea liberica and Coffea excelsea from Cavite were collected and assessed for the distribution of fungi with the potential to produce ochratoxin A (OTA). The presence of fungal species was evaluated both before and after surface sterilization. There were remarkable ecological and varietal differences in the population of OTA-producing species from the five provinces. Aspergillus ochraceus, A. westerdijkiae, and Penicillium verruculosum were detected from Arabica in Benguet and Ifugao while Aspergillus carbonarius, Aspergillus niger, and Aspergillus japonicus were isolated in Excelsa, Liberica, and Robusta varieties from Abra, Cavite, and Davao. Contamination by Aspergillus and Penicillium species was found on 59 and 19 %, respectively, of the 57 samples from five provinces. After disinfection with 1% sodium hypochlorite, the levels of infection by Aspergillus and Penicillium fell to 40 and 17%, respectively. A total of 1184 fungal isolates were identified to species level comprising Aspergillus sections Circumdati (four species), Clavati (one), Flavi (one), Fumigati (one), Nigri (three), and Terrie (one). Within section Circumdati, 70% of A. ochraceus produced OTA as high as 16238 ng g(-1) while 40% of A. westerdijkiae produced maximum OTA of 36561 ng g(-1) in solid agar. Within section Nigri, 16.76% of A. niger produced OTA at the highest 18439 ng g(-1), 10% of A. japonicus at maximum level of 174 ng g(-1), and 21.21% of A. carbonarius yielded maximum OTA of 1900 ng g(-1). Of the 12 species of Penicillium isolated, P. verruculosum was ochratoxigenic, with a maximum OTA production of 12 ng g(-1). PMID- 26814978 TI - A High-Sensitivity and Low-Power Theranostic Nanosystem for Cell SERS Imaging and Selectively Photothermal Therapy Using Anti-EGFR-Conjugated Reduced Graphene Oxide/Mesoporous Silica/AuNPs Nanosheets. AB - A high-sensitivity and low-power theranostic nanosystem that combines with synergistic photothermal therapy and surface-enhanced Raman scattering (SERS) mapping is constructed by mesoporous silica self-assembly on the reduced graphene oxide (rGO) nanosheets with nanogap-aligned gold nanoparticles (AuNPs) encapsulated and arranged inside the nanochannels of the mesoporous silica layer. Rhodamine 6G (R6G) as a Raman reporter is then encapsulated into the nanochannels and anti-epidermal growth factor receptor (EGFR) is conjugated on the nanocomposite surface, defined as anti-EGFR-PEG-rGO@CPSS-Au-R6G, where PEG is polyethylene glycol and CPSS is carbon porous silica nanosheets. SERS spectra results show that rGO@CPSS-Au-R6G enhances 5 * 10(6) magnification of the Raman signals and thus can be applied in the noninvasive cell tracking. Furthermore, it displays high sensitivity (detection limits: 10(-8) m R6G solution) due to the "hot spots" effects by the arrangements of AuNPs in the nanochannels of mesoporous silica. The highly selective targeting of overexpressing EGFR lung cancer cells (A549) is observed in the anti-EGFR-PEG-rGO@CPSS-Au-R6G, in contrast to normal cells (MRC-5). High photothermal therapy efficiency with a low power density (0.5 W cm(-2) ) of near-infrared laser can be achieved because of the synergistic effect by conjugated AuNPs and rGO nanosheets. These results demonstrate that the anti-EGFR-PEG-rGO@CPSS-Au-R6G is an excellent new theranostic nanosystem with cell targeting, cell tracking, and photothermal therapy capabilities. PMID- 26814979 TI - Is Tibiofemoral or Patellofemoral Alignment or Trochlear Morphology Associated With Patellofemoral Osteoarthritis? A Systematic Review. AB - OBJECTIVE: We conducted a systematic review to evaluate the associations of knee alignment or trochlear morphology (measured on imaging) with presence, severity, onset, and/or progression of patellofemoral osteoarthritis (PFOA). METHODS: We prospectively registered our protocol with PROSPERO (International prospective register of systematic reviews) and followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to report this review. We searched 10 electronic databases, screened citing articles, and reviewed reference lists. We extracted data and evaluated methodologic quality. Due to study design heterogeneity, we used a best-evidence synthesis to summarize the evidence. RESULTS: We included 16 publications (2,892 participants, 66% women) after removing 4 papers that did not meet our threshold for methodologic quality. There were 11 cross-sectional and 5 longitudinal papers. The target population was knee OA in 11 studies, PFOA in 2 studies, and other knee conditions in 3 studies. Alignment or morphology was measured using radiographs in 8 studies, magnetic resonance imaging in 7 studies, and computed tomography in 2 papers. Limitations include substantial heterogeneity in samples and methods, short followup times in longitudinal studies, and a small number of studies that specifically recruited participants with PFOA. CONCLUSION: There is strong evidence that PFOA is associated with both trochlear morphology and frontal plane knee alignment, while evidence is limited but consistent in the sagittal and axial planes. These findings suggest that alignment should be evaluated clinically in individuals with PFOA. Clinical interventions targeting knee alignment warrant further investigation. PMID- 26814980 TI - Potential Limitations of the Newly Proposed Knee Osteoarthritis Composite Symptom Score: Comment on the Article by Lo et al. PMID- 26814981 TI - Effects of Heme Electronic Structure and Distal Polar Interaction on Functional and Vibrational Properties of Myoglobin. AB - We analyzed the oxygen (O2) and carbon monoxide (CO) binding properties, autoxidation reaction rate, and FeO2 and FeCO vibrational frequencies of the H64Q mutant of sperm whale myoglobin (Mb) reconstituted with chemically modified heme cofactors possessing a variety of heme Fe electron densities (rho(Fe)), and the results were compared with those for the previously studied native [Shibata, T. et al. J. Am. Chem. Soc. 2010, 132, 6091-6098], and H64L [Nishimura, R. et al. Inorg. Chem. 2014, 53, 1091-1099], and L29F [Nishimura, R. et al. Inorg. Chem. 2014, 53, 9156-9165] mutants in order to elucidate the effect of changes in the heme electronic structure and distal polar interaction contributing to stabilization of the Fe-bound ligand on the functional and vibrational properties of the protein. The study revealed that, as in the cases of the previously studied native protein [Shibata, T. et al. Inorg. Chem. 2012, 51, 11955-11960], the O2 affinity and autoxidation reaction rate of the H64Q mutant decreased with a decrease in rho(Fe), as expected from the effect of a change in rho(Fe) on the resonance between the Fe(2+)-O2 bond and Fe(3+)-O2(-)-like species in the O2 form, while the CO affinity of the protein is independent of a change in rho(Fe). We also found that the well-known inverse correlation between the frequencies of Fe-bound CO (nu(CO)) and Fe-C (nu(FeC)) stretching [Li, X.-Y.; Spiro, T. G. J. Am. Chem. Soc. 1988, 110, 6024-6033] is affected differently by changes in rho(Fe) and the distal polar interaction, indicating that the effects of the two electronic perturbations due to the chemical modification of a heme cofactor and the replacement of nearby amino acid residues on the resonance between the two alternative canonical forms of the FeCO fragment in the protein are slightly different from each other. These findings provide a new insight for deeper understanding of the functional regulation of the protein. PMID- 26814982 TI - Oxidative ring-opening of ferrocenylcyclopropylamines to N-ferrocenylmethyl beta hydroxyamides. AB - The in situ reduction of ferrocenyl cyclopropylimines to the corresponding amines triggers a facile oxidative ring-opening to yield the formal four-electron oxidation products: N-ferrocenylmethyl beta-hydroxyamides. This process is believed to proceed via generation of a ferrocinium ion in the presence of air, leading to facile formation of a distonic radical cation that is ultimately trapped by oxygen. PMID- 26814984 TI - Apheresis platelets are more frequently associated with adverse reactions than pooled platelets both in recipients and in donors: a study from French hemovigilance data. AB - BACKGROUND: Controversy exists regarding the safety of the different types of platelet (PLT) concentrates. This study was aimed at comparing the rate of adverse reactions associated with apheresis PLT concentrates (APCs) and pooled PLT concentrates (PPCs) both in donors and in recipients. STUDY DESIGN AND METHODS: From the French national hemovigilance system, types and numbers of recipient adverse reactions were compared over a period from 2009 to 2011. Donor adverse reactions were available for 2010 and 2011. This study involved 23 of 26 French regions. Main outcomes were the rates of adverse reaction in recipients and serious adverse reaction in donors. RESULTS: There were 790,854 PLT transfusions during the study period (477,747 [60%] with APCs, 313,107 [40%] with PPCs). APCs were associated with more adverse reactions (6244 vs. 2469 per 1,000,000, p < 0.001) and more severe and life-threatening reactions (respectively, 241 vs. 131 per 1,000,000, p < 0.001; and 182 vs. 121 per 1,000,000, p = 0.04). Mortality rates due to an adverse transfusion reaction were similar (15 vs. 6 per 1,000,000, p = 0.5). In donors, the number of whole blood (WB) donations was 4,722,685 whereas 266,095 apheresis procedures were performed. Serious adverse reactions were more frequent for apheresis procedures than for WB donations (5445 vs. 803 per 1,000,000, p < 0.001). CONCLUSION: Our findings suggest that apheresis PLTs may be more hazardous than pooled PLTs both in recipients and in donors. This study calls for randomized trials to confirm or refute these results. PMID- 26814983 TI - Ambivalence: Prerequisite for success in motivational interviewing with adolescents? AB - BACKGROUND AND AIMS: The exploration and resolution of ambivalence play an essential role in motivational interviewing (MI) theory. However, most adolescent MI studies have not examined ambivalence as a contributor to behaviour change. This paper reviewed research findings on the role of ambivalence in the adolescent change process. METHODS AND RESULTS: We undertook a narrative review of the published empirical and theoretical literature on ambivalence and mechanisms of change in MI for adolescents and found that current MI evaluations appear not to have access to reliable and valid measures of ambivalence in adolescence or neuroimaging methods to evaluate the mechanisms of treatment response. CONCLUSIONS: Improved instrumentation is needed to assess adolescents' ambivalence in clinical and research settings. Innovative methodology, including neuroimaging, may help identify factors mediating relationships between adolescents' ambivalence and treatment response. PMID- 26814985 TI - Prevalence of alterations in chest computerized tomography in patients with head and neck cancer. AB - OBJECTIVE: to assess the prevalence of abnormalities found by computed tomography (CT) of the chest in patients with squamous cell carcinoma of the head and neck. METHODS: we retrospectively analyzed chest CT exams of 209 patients with squamous cell carcinoma of the head and neck. The CT findings were stratified as inflammatory / infectious, parenchymal, nodular uncharacteristic and nodular metastatic/tumoral. RESULTS: alterations were diagnosed in 66.6% of patients. Of these, 25.3% represented emphysema; 18.8%, uncharacteristic micronodules; 12.9%, metastases; 11.9%, thoracic lymph node enlargements; and in 6.6% we detected active pulmonary tuberculosis or its sequelae, pneumonia or inflammatory / infectious signs and pleural thickening or effusion. CONCLUSION: the prevalence of exams with alterations and the considerable rate of detected metastases indicate that chest CT should be required for diagnostic and / or staging in cases of head and neck cancer. PMID- 26814986 TI - Total esophagogastrectomy in the neoplasms of the esophagus and esofagogastric junction: when must be indicated? AB - OBJECTIVE: to analyse the indications and results of the total esophagogastrectomy in cancers of the distal esophagus and esophagogastric junction. METHODS: twenty patients with adenocarcinomas were operated with a mean age of 55 +/- 9.9 years (31-70 years), and 14 cases were male (60%). Indications were 18 tumors of the distal esophagus and esophagogastric junction (90%) and two with invasion of gastric fundus (10%) in patients with previous gastrectomy. Preoperative colonoscopy to exclude colonic diseases was performed in ten cases. RESULTS: the surgical technique consisted of median laparotomy and left cervicotomy, followed by transhiatal esophagectomy associated with D2 lymphadenectomy. The reconstructions were performed with eight esophagocoloduodenoplasty and the others were Roux-en-Y esophagocolojejunoplasty to prevent the alkaline reflux. Three cases were stage I / II, while 15 cases (85%) were stages III / IV, reflecting late diagnosis of these tumors. The operative mortality was 5 patients (25%): a mediastinitis secondary to necrosis of the transposed colon, abdominal cellulitis secondary to wound infection, severe pneumonia, an irreversible shock and sepsis associated with colojejunal fistula. Four patients died in the first year after surgery: 3 (15%) were due to tumor recurrence and 1 (5%) secondary to bronchopneumonia. The 5-year survival was 15%. CONCLUSION: the total esophagogastrectomy associated with esophagocoloplasty has high morbidity and mortality, requiring precise indication, and properly selected patients benefit from the surgery, with the risk-benefit acceptable, contributing to increased survival and improved quality of life. PMID- 26814987 TI - Plastic surgery in chest wall reconstruction: relevant aspects - case series. AB - OBJECTIVE: to discuss the participation of Plastic Surgery in the reconstruction of the chest wall, highlighting relevant aspects of interdisciplinaryness. METHODS: we analyzed charts from 20 patients who underwent extensive resection of the thoracic integument, between 2000 and 2014, recording the indication of resection, the extent and depth of the raw areas, types of reconstructions performed and complications. RESULTS: among the 20 patients, averaging 55 years old, five were males and 15 females. They resections were: one squamous cell carcinoma, two basal cell carcinomas, five chondrosarcomas and 12 breast tumors. The extent of the bloody areas ranged from 4x9 cm to 25x40 cm. In 12 patients the resection included the muscular plane. In the remaining eight, the tumor removal achieved a total wall thickness. For reconstruction we used: one muscular flap associated with skin grafting, nine flaps and ten regional fasciocutaneous flaps. Two patients undergoing reconstruction with fasciocutaneous flaps had partially suffering of the flap, solved with employment of a myocutaneous flap. The other patients displayed no complications with the techniques used, requiring only one surgery. CONCLUSION: the proper assessment of local tissues and flaps available for reconstruction, in addition to the successful integration of Plastic Surgery with the specialties involved in the treatment, enable extensive resections of the chest wall and reconstructions that provide patient recovery. PMID- 26814989 TI - Modified pubovaginal sling technique in the surgical management of female stress urinary incontinence. AB - OBJECTIVE: To assess the application of aponeurotic sling by a modified technique with direct visualization of needles in patients with stress urinary incontinence. METHODS: we applied the Kings Health Questionnaire (KHQ) for quality of life, gynecological examination, urinalysis I and urine culture approximately seven days prior to the urodynamic study (UDS) and the one-hour PAD test in patients undergoing making aponeurotic sling with its passing through the retropubic route with direct visualization of the needle, PAD test and King's Health Questionnaire before and after surgery. RESULTS: The mean age was 50.6 years, BMI of 28 and Leak Pressure (LP) 58,5 cm H2O; 89% were Caucasian. Forty six of them were monitored for three and six months, 43 for 12 months. The objective cure rate at 12 months postoperatively was approximately 93.5%. In evaluating quality of life, we observed a significant improvement in 12 months postoperatively compared with the preoperative period. There was no no urethral/bladder injury. As adverse results, we had one persistent urinary retention (2.3%), who was submitted to urethrolysis, currently without incontinence. CONCLUSION: The proposed procedure is safe as for the risk of bladder or urethral injuries, promoting significant improvement in quality of life and objective cure. PMID- 26814988 TI - Epidemiological profile and postoperative complications of women undergoing gynecological surgery in a reference center in the northern Brazilian legal Amazon. AB - OBJECTIVE: To evaluate the epidemiological profile and the operative complications of patients undergoing gynecological operations for benign diseases in a tertiary public hospital in the state of Roraima, Brazil. METHODS: We conducted a retrospective survey through the analysis of 518 records of patients submitted to gynecological operations between January and June 2012. We included the three major operations during this period (n = 175): hysterectomy, colpoperineoplasty and suburethral sling placement. We excluded 236 cases of tubal ligation and 25 cases where it was not possible to access to medical records. RESULTS: The mean age was 47.6 years; the education level of most patients was completed junior high (36.6%); 77% were from the State capital, 47.4% were in stable relationships and 26.3% were housewives. The majority of patients had given birth three or more times (86.6%), with previous vaginal delivery in 50.2%, and cesarean delivery, 21%. The main diagnostic indications for surgical treatment were uterine myoma (46.3%), urinary incontinence (27.4%) and genital dystopias (17.7%). We found three cases (1.7%) of high-grade intraepithelial lesions on Pap smear. The most common procedure was total hysterectomy (19.8%), 15.5% vaginally. The most common complication was wound infection (2.2%). CONCLUSION: Women undergoing gynecological operations due to benign disease had a mean age of 47 years, most had levels of basic education, came from the capital, were in stable relationships, predominantly housewives, multiparous and showed low operative complication rates. PMID- 26814990 TI - Epidemiological analysis of polytrauma patients with kidney injuries in a university hospital. AB - OBJECTIVE: To analyze the characteristics of trauma patients with renal lesions treated at a university hospital in Curitiba. METHODS: We conducted a retrospective, cross-sectional study guided by review of medical records of trauma victims who underwent surgical treatment. The variables analyzed were age, gender, mechanism of injury, degree of kidney damage, conduct individualized according to the degree of renal injury, associated injuries, complications and deaths. We classified lesions according to the American Association of Trauma Surgery (TSAA). RESULTS: We analyzed 794 records and found renal lesions in 33 patients, with mean age 29.8 years, most (87.8%) being male. Penetrating trauma accounted for 84.8% of cases. The most common renal injuries were grade II (33.3%), followed by grade I (18.1%), III, IV and V. Nephrectomy treated 45.4% of injuries, 73.3% being total nephrectomy, and 45.4% by nephrorraphy. In 9% treatment was non-surgical. Only 12.1% of patients had isolated renal lesions. Complications ensued in 15.1% and mortality was 6.06%. CONCLUSION: The surgical approach was preferred due to penetrating trauma mechanism. We achieved low rates of complications and deaths, and neither case could be directly related to kidney damage, and there were patients with multiple lesions. In this sample, we could not observe a direct relationship between kidney damage and complications, deaths or the type of conduct employed. PMID- 26814991 TI - Analysis of natural history of the diaphragmatic injury on the right in mice. AB - OBJECTIVE: to evaluate natural evolution of right diaphragmatic injury after the surgical removal of a portion from hemi diaphragm. METHODS: the animals were submitted to a surgical removal of portion from right hemi diaphragm by median laparotomy. The sample consists of 42 animals being 2 animals from pilot project and 40 operated animals. And the variables of the study were herniation, liver protection, healing, persistent diaphragm injury, evaluation of 16 channels tomography and the variables "heart rate" and "weight". RESULTS: we analyzed 40 mice, we had two post-operative deaths; we had 17 animals in this group suffered from herniation (42.5%) and 23 animals didn't suffer from herniation (57.5%). Analyzing the tomography as image method in the evaluation of diaphragmatic hernia, we had as a method with good sensitivity (78.6%), good specificity (90.9%), and good accuracy (86.1%) when compared to necropsy. CONCLUSION: there was a predominance of healing of right hemi diaphragm, the size of initial injury didn't have influence on occurrence of the liver protection or hernia in mice. PMID- 26814992 TI - Evaluation of liver regeneration diet supplemented with omega-3 fatty acids: experimental study in rats. AB - OBJECTIVE: to evaluate liver regeneration in rats after partial hepatectomy of 60% with and without action diet supplemented with fatty acids through the study of the regenerated liver weight, laboratory parameters of liver function and histological study. METHODS: thirty-six Wistar rats, males, adults were used, weighing between 195 and 330 g assigned to control and groups. The supplementation group received the diet by gavage and were killed after 24h, 72h and seven days. Evaluation of regeneration occurred through analysis of weight gain liver, serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyltranspeptidase, and mitosis of the liver stained with H&E. RESULTS: the diet supplemented group showed no statistical difference (p>0.05) on the evolution of weights. Administration of fatty acids post-hepatectomy had significant reduction in gamma glutamyltransferase levels and may reflect liver regeneration. Referring to mitotic index, it did not differ between period of times among the groups. CONCLUSION: supplementation with fatty acids in rats undergoing 60% hepatic resection showed no significant interference related to liver regeneration. PMID- 26814993 TI - Effect of Carapa guianensis Aublet (Andiroba) and Orbignya phalerata (Babassu) in colonic healing in rats. AB - OBJECTIVE: to evaluate the healing effect of the babassu aqueous extract and andiroba oil on open wounds in the cecum of rats. METHODS: fifty-four Wistar rats were divided into three groups of 18: 1) babassu group with application of aqueous extract of babassu; 2) andiroba group with application of the oil; and 3) control group, with application of saline solution. All procedures were done by gavage. Each group was divided into three subgroups of six animals according to the observation period of 7, 14 or 21 days. From each animal was removed caecum fragment of 1.5cm2 diameter. The areas of the lesions were analyzed macroscopically and resected specimens by light microscopy using hematoxylin eosin and Masson's trichrome. RESULTS: abscess and infection were observed in two aroeira group animals, and in one only hematoma. In relationship to adhesions degree, babassu group had higher incidence of grade II while in the control and aroeira groups predominated adhesions grade I. On microscopic examination on day 7 fibroblast proliferation was greater in aroeira and lower in babassu group (p=0.028). On the 14th day polymorphonuclear were less pronounced in babassu (p=0.007). As for the resistance test of air insufflation, it was observed that in all andiroba group in all tested days showed be higher. As for collagen, on the 7th day it was present in 100% of animals of aroeira group. On the 14th day was more pronounced in the control group and at day 21 similar results were found in the control and aroeira groups. CONCLUSION: animals in babassu and andiroba groups showed better cecum healing compared to the control group. PMID- 26814994 TI - Construction and validation of a surgical skills assessment tool for general surgery residency program. AB - OBJECTIVE: To develop and validate an instrument for measuring the acquisition of technical skills in conducting operations of increasing difficulty for use in General Surgery Residency (GSR) programs. METHODS: we built a surgical skills assessment tool containing 11 operations in increasing levels of difficulty. For instrument validation we used the face validity method. Through an electronic survey tool (Survey MonKey(r)) we sent a questionnaire to Full and Emeritus members of the Brazilian College of Surgeons--CBC--all bearers of the CBC Specialist Title. RESULTS: Of the 307 questionnaires sent we received 100 responses. For the analysis of the data collected we used the Cronbach's alpha test. We observed that, in general, the overall alpha presented with values near or greater than 0.70, meaning good consistency to assess their points of interest. CONCLUSION: The evaluation instrument built was validated and can be used as a method of assessment of technical skill acquisition in the General Surgery Residency programs in Brazil. PMID- 26814995 TI - System to outline the graduate students. AB - OBJECTIVE: to evaluate the system to outline the graduate students from the Post Graduate Programs of CAPES Medicine III area. METHOD: it was analyzed the book of indicators and the Document of Area of the Post-Graduate Programs of Surgery, also checking the literature about this issue. RESULTS: there was a paucity of data from most of the programs, as regards to the methods for evaluation of graduate students. The current system lacks a standard and an institutional support to outline the graduate students. In the public system there is a concentration of postgraduate students in Medicine; however, they represent a small part of those Brazilians students who finished their graduation courses in Medicine. In the current context, the quest for the post graduate courses and consequently for a research field or even a teaching career, has been replaced by the private sector jobs and the labor market, both in non-academic assistance activities. CONCLUSION: it is imperative to establish not only science and technology innovation policies but also educational and health policies acting harmoniously and stimulating the qualification and the teaching career, improving the post-graduate courses. It is necessary to develop a single form under the institutional guidance of CAPES with the conception of a National Program for Graduate Student in order to consolidate guidelines to mapping the graduate students of post-graduate programs in surgery, in our country. PMID- 26814996 TI - Device model for training of laparoscopic surgical skills. AB - The authors present a especially constructed, lightweight, collapsible, portable and low cost model device for skills training in laparoscopic. PMID- 26814997 TI - Obtention of injectable platelets rich-fibrin (i-PRF) and its polymerization with bone graft: technical note. AB - The use of autologous platelet concentrates, represent a promising and innovator tools in the medicine and dentistry today. The goal is to accelerate hard and soft tissue healing. Among them, the platelet-rich plasma (PRP) is the main alternative for use in liquid form (injectable). These injectable form of platelet concentrates are often used in regenerative procedures and demonstrate good results. The aim of this study is to present an alternative to these platelet concentrates using the platelet-rich fibrin in liquid form (injectable) and its use with particulated bone graft materials in the polymerized form. PMID- 26814998 TI - An eDNA Assay to Monitor a Globally Invasive Fish Species from Flowing Freshwater. AB - Ponto-Caspian gobies are a flock of five invasive fish species that have colonized freshwaters and brackish waters in Europe and North America. One of them, the round goby Neogobius melanostomus, figures among the 100 worst invaders in Europe. Current methods to detect the presence of Ponto-Caspian gobies involve catching or sighting the fish. These approaches are labor intense and not very sensitive. Consequently, populations are usually detected only when they have reached high densities and when management or containment efforts are futile. To improve monitoring, we developed an assay based on the detection of DNA traces (environmental DNA, or eDNA) of Ponto-Caspian gobies in river water. The assay specifically detects invasive goby DNA and does not react to any native fish species. We apply the assay to environmental samples and demonstrate that parameters such as sampling depth, sampling location, extraction protocol, PCR protocol and PCR inhibition greatly impact detection. We further successfully outline the invasion front of Ponto-Caspian gobies in a large river, the High Rhine in Switzerland, and thus demonstrate the applicability of the assay to lotic environments. The eDNA assay requires less time, equipment, manpower, skills, and financial resources than the conventional monitoring methods such as electrofishing, angling or diving. Samples can be taken by untrained individuals, and the assay can be performed by any molecular biologist on a conventional PCR machine. Therefore, this assay enables environment managers to map invaded areas independently of fishermen's' reports and fish community monitorings. PMID- 26814999 TI - Cerebrospinal fluid leakage from the umbilicus: Case report and literature review. AB - INTRODUCTION: Shunt catheters within the peritoneal cavity have migrated through and perforated almost all the intra-abdominal hollow viscera. An umbilical cerebrospinal fluid fistula following a ventriculoperitoneal shunt is an extremely rare complication. CASE PRESENTATION: We report a 8-month-old infant who presented with leak of clear fluid from the umbilicus, seven months after a ventriculoperitoneal shunt operation. We could not see distal tip of the shunt on examination. After the operation, the patient's follow-up was uneventful. DISCUSSION: The direct effect of CSF and VP shunt, such as chronic irrigation, silicon allergy, foreign body reaction, may cause sterile inflammation on the abdominal structures and this inflammation may soften tissue and cause CFS leakage and VP shunt extrusion. CONCLUSION: If the distal tip detected on umbilical region, these patients should be examined frequently for umbilical shunt pathologies, especially infants. PMID- 26815000 TI - Neurodevelopmental Outcomes in Infants with Retinopathy of Prematurity and Bevacizumab Treatment. AB - PURPOSE: The current study aims to investigate the neurodevelopment of premature infants after intravitreal injections of bevacizumab (IVB) for the treatment of retinopathy of prematurity (ROP) up to the age of 2 years. METHODS: The study design was retrospective observational case series conducted at an institutional referral center. Infants with type 1 ROP were classified into 3 groups: laser only, IVB only, and a combination of IVB and laser treatment. Main Outcome Measures were neurodevelopmental outcomes of the patients after treatment were assessed by Bayley Scales for Infant Development. RESULTS: Sixty-one patients who finished the neurodevelopmental survey were included. No detrimental effects on neurodevelopment were found in IVB group compared with the patients who received laser treatment only. The patients in the IVB + laser group had a higher incidence of significant mental (p = 0.028) and psychomotor (p = 0.002) impairment at 24 months than the patients in the laser group. The odds ratio of having severe psychomotor defects in the IVB + laser group was 5.3 compared with the laser group (p = 0.041). The causal source for the differences that were detected remained unknown due to lack of randomization in the study and accompanying bias in patient selection. CONCLUSIONS: Two years after laser and/or intravitreal injections of bevacizumab for infants with retinopathy of prematurity, no difference on neurodevelopment for those who received only bevacizumab versus only laser treatment were found. Those infants who required rescue therapy with laser or bevacizumab injection after initial, unsuccessful treatment showed some detrimental, neurodevelopmental effects. PMID- 26815001 TI - Utilising copper screen-printed electrodes (CuSPE) for the electroanalytical sensing of sulfide. AB - A mediatorless sulfide electrochemical sensing platform utilising a novel nanocopper-oxide screen-printed electrodes (CuSPE) is reported for the first time. The state-of-the-art screen-printed electrochemical sensors demonstrate their capability to quantify sulfide within both the presence and absence of an array of interferents with good levels of sensitivity and repeatability. The direct sensing (using linear sweep voltammetry) of sulfide utilising the CuSPEs provides a mediatorless approach for the detection of sulfide, yielding useful analytical signatures that can be successfully quantified. The proposed novel protocol using the CuSPEs is successfully applied to the sensing of sulfide within drinking water exhibiting a high level of recovery. PMID- 26815002 TI - Human adipose derived mesenchymal stromal cells transduced with GFP lentiviral vectors: assessment of immunophenotype and differentiation capacity in vitro. AB - Adipose derived mesenchymal stromal/stem cells (ASCs) are a heterogeneous population characterized by (a) their ability to adhere to plastic; (b) immunophenotypic expression of certain cell surface markers, while lacking others; and (c) the capacity to differentiate into lineages of mesodermal origin including osteocytes, chondrocytes and adipocytes. The long-term goal is to utilize these cells for clinical translation into cell-based therapies. However, preclinical safety and efficacy need to be demonstrated in animal models. ASCs can also be utilized as biological vehicles for vector-based gene delivery systems, since they are believed to home to sites of inflammation and infection in vivo. These factors motivated the development of a labelling system for ASCs using lentiviral vector-based green fluorescent protein (GFP) transduction. Human ASCs were transduced with GFP-expressing lentiviral vectors. A titration study determined the viral titer required to transduce the maximum number of ASCs. The effect of the transduced GFP lentiviral vector on ASC immunophenotypic expression of surface markers as well as their ability to differentiate into osteocytes and adipocytes were assessed in vitro. A transduction efficiency in ASC cultures of approximately 80 % was observed with an MOI of ~118. No significant immunophenotypic differences were observed between transduced and non-transduced cells and both cell types successfully differentiated into adipocytes and osteocytes in vitro. We obtained >80 % transduction of ASCs using GFP lentiviral vectors. Transduced ASCs maintained plastic adherence, demonstrated ASC immunophenotype and the ability to differentiate into cells of the mesodermal lineage. This GFP-ASC transduction technique offers a potential tracking system for future pre-clinical studies. PMID- 26815003 TI - Motion-Based pH Sensing Based on the Cartridge-Case-like Micromotor. AB - In this paper, we report a novel cartridge-case-like micromotor. The micromotor, which is fabricated by the template synthesis method, consists of a gelatin shell with platinum nanoparticles decorating its inner surface. Intriguingly, the resulting cartridge-case-like structure exhibits a pH-dependent "open and close" feature, which originates from the pH responsiveness of the gelatin material. On the basis of the catalytic activity of the platinum nanoparticle inside the gelatin shell, the resulting cartridge-case-like structure is capable of moving autonomously in the aqueous solution containing the hydrogen peroxide fuel. More interestingly, we find out that the micromotor can be utilized as a motion-based pH sensor over the whole pH range. The moving velocity of the micromotor increases monotonically with the increase of pH of the analyte solution. Three different factors are considered to be responsible for the proportional relation between the motion speed and pH of the analyte solution: the peroxidase-like and oxidase-like catalytic behavior of the platinum nanoparticle at low and high pH, the volumetric decomposition of the hydrogen peroxide under the basic condition and the pH-dependent catalytic activity of the platinum nanoparticle caused by the swelling/deswelling behavior of the gelatin material. The current work highlights the impact of the material properties on the motion behavior of a micromotor, thus paving the way toward its application in the motion-based sensing field. PMID- 26815008 TI - A Content Analysis of Quantitative Research in Journal of Marital and Family Therapy: A 10-Year Review. AB - We examined the trends of quantitative research over the past 10 years in the Journal of Marital and Family Therapy (JMFT). Specifically, within the JMFT, we investigated the types and trends of research design and statistical analysis within the quantitative research that was published in JMFT from 2005 to 2014. We found that while the amount of peer-reviewed articles have increased over time, the percentage of quantitative research has remained constant. We discussed the types and trends of statistical analysis and the implications for clinical work and training programs in the field of marriage and family therapy. PMID- 26815007 TI - Is received dose from ingested soil independent of soil PAH concentrations? Animal model results. AB - Polycyclic aromatic hydrocarbon (PAH) bioavailability from ingested soils will vary between soils; however, the nature of this variation is not well characterized. A juvenile swine model was used to link external exposure to internal benzo[a]pyrene (BaP) and anthracene exposure following oral PAH ingestion of 27 different impacted site soils, soots, or spiked artificial soils. Internal exposure of BaP and anthracene, represented by area under the plasma time curve, did not relate to soil concentration in impacted site soils, but did relate in spiked artificial soil. Point of departure modeling identified soil PAH concentrations greater than 1900 mg kg(-1) as the point where area under the curve becomes proportional to external dose. A BaP internal exposure below 1900 mg kg(-1) had an upper 95% confidence interval estimate of 33% of external exposure. Weak relationships between soil:simulated gastrointestinal fluid PAH partitioning and area under the curve values suggest that differences in internal PAH exposure between soils may not be dominated by differences in PAH partitioning. The data seem to best support exposure assessment assuming constant internal PAH exposure below soil concentrations of 1900 mg kg(-1) . However, because constant internal exposure would challenge several existing paradigms, a bioavailability estimate of 33% of the external exposure is suggested as a likely workable solution. Environ Toxicol Chem 2016;35:2261-2269. (c) 2016 SETAC. PMID- 26815004 TI - Dietary Nitrate Lowers Blood Pressure: Epidemiological, Pre-clinical Experimental and Clinical Trial Evidence. AB - Nitric oxide (NO), a potent vasodilator critical in maintaining vascular homeostasis, can reduce blood pressure in vivo. Loss of constitutive NO generation, for example as a result of endothelial dysfunction, occurs in many pathological conditions, including hypertension, and contributes to disease pathology. Attempts to therapeutically deliver NO via organic nitrates (e.g. glyceryl trinitrate, GTN) to reduce blood pressure in hypertensives have been largely unsuccessful. However, in recent years inorganic (or 'dietary') nitrate has been identified as a potential solution for NO delivery through its sequential chemical reduction via the enterosalivary circuit. With dietary nitrate found in abundance in vegetables this review discusses epidemiological, pre-clinical and clinical data supporting the idea that dietary nitrate could represent a cheap and effective dietary intervention capable of reducing blood pressure and thereby improving cardiovascular health. PMID- 26815005 TI - Mg(2+) differentially regulates two modes of mitochondrial Ca(2+) uptake in isolated cardiac mitochondria: implications for mitochondrial Ca(2+) sequestration. AB - The manner in which mitochondria take up and store Ca(2+) remains highly debated. Recent experimental and computational evidence has suggested the presence of at least two modes of Ca(2+) uptake and a complex Ca(2+) sequestration mechanism in mitochondria. But how Mg(2+) regulates these different modes of Ca(2+) uptake as well as mitochondrial Ca(2+) sequestration is not known. In this study, we investigated two different ways by which mitochondria take up and sequester Ca(2+) by using two different protocols. Isolated guinea pig cardiac mitochondria were exposed to varying concentrations of CaCl2 in the presence or absence of MgCl2. In the first protocol, A, CaCl2 was added to the respiration buffer containing isolated mitochondria, whereas in the second protocol, B, mitochondria were added to the respiration buffer with CaCl2 already present. Protocol A resulted first in a fast transitory uptake followed by a slow gradual uptake. In contrast, protocol B only revealed a slow and gradual Ca(2+) uptake, which was approximately 40 % of the slow uptake rate observed in protocol A. These two types of Ca(2+) uptake modes were differentially modulated by extra-matrix Mg(2+). That is, Mg(2+) markedly inhibited the slow mode of Ca(2+) uptake in both protocols in a concentration-dependent manner, but not the fast mode of uptake exhibited in protocol A. Mg(2+) also inhibited Na(+)-dependent Ca(2+) extrusion. The general Ca(2+) binding properties of the mitochondrial Ca(2+) sequestration system were reaffirmed and shown to be independent of the mode of Ca(2+) uptake, i.e. through the fast or slow mode of uptake. In addition, extra-matrix Mg(2+) hindered Ca(2+) sequestration. Our results indicate that mitochondria exhibit different modes of Ca(2+) uptake depending on the nature of exposure to extra matrix Ca(2+), which are differentially sensitive to Mg(2+). The implications of these findings in cardiomyocytes are discussed. PMID- 26815010 TI - Conversations in the operating room: history of the development of a promising new compound for the treatment of premature ejaculation. PMID- 26815009 TI - Clinical significance of circulating plasma DNA in gastric cancer. AB - With the progression of molecular techniques, the detection of circulating plasma DNA (cpDNA) is clinically feasible. However, the role of the cpDNA levels in gastric cancer is not well understood. This study assessed the mutational profile in primary tumors and clarified the clinical utility of quantitative and qualitative cpDNA alterations in 277 patients with advanced gastric cancer. The concentrations of cpDNA were measured by TaqMan qPCR, and 68 mutations in 8 genes were studied for cpDNA mutations. The median cpDNA concentrations in patients with stages I, II, and III gastric cancer were 3979, 3390 and 4278 copies/mL, respectively, and increased to 11,380 copies/mL in patients with Stage IV gastric cancer (p < 0.001). Among the 35 patients harboring cpDNA mutations, Stage IV patients (100%) were more likely to display high cpDNA levels than were Stage I (33.3%), II (75%) and III patients (66.7%) (p = 0.037). Patients displaying high cpDNA levels were more likely to experience peritoneal recurrence and exhibited significantly lower 5-year overall survival rates (39.2% vs. 45.8%, p = 0.039) than did patients displaying low cpDNA levels. Only for late stage (Stages III or IV) gastric cancer, patients harboring cpDNA mutations were more likely to experience vascular invasion (20% vs. 2.4%, p = 0.036) and exhibited a lower 5 year overall survival rate than did those lacking cpDNA mutations (5.6% vs. 31.5%, p = 0.028). High cpDNA levels are associated with peritoneal recurrence and poor prognosis in patients with advanced gastric cancer; harboring cpDNA mutations is associated with poor prognosis among patients with late stage gastric cancer. PMID- 26815006 TI - Seven key actions to eradicate rheumatic heart disease in Africa: the Addis Ababa communique. AB - Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain major causes of heart failure, stroke and death among African women and children, despite being preventable and imminently treatable. From 21 to 22 February 2015, the Social Cluster of the Africa Union Commission (AUC) hosted a consultation with RHD experts convened by the Pan-African Society of Cardiology (PASCAR) in Addis Ababa, Ethiopia, to develop a 'roadmap' of key actions that need to be taken by governments to eliminate ARF and eradicate RHD in Africa. Seven priority areas for action were adopted: (1) create prospective disease registers at sentinel sites in affected countries to measure disease burden and track progress towards the reduction of mortality by 25% by the year 2025, (2) ensure an adequate supply of high-quality benzathine penicillin for the primary and secondary prevention of ARF/RHD, (3) improve access to reproductive health services for women with RHD and other non-communicable diseases (NCD), (4) decentralise technical expertise and technology for diagnosing and managing ARF and RHD (including ultrasound of the heart), (5) establish national and regional centres of excellence for essential cardiac surgery for the treatment of affected patients and training of cardiovascular practitioners of the future, (6) initiate national multi-sectoral RHD programmes within NCD control programmes of affected countries, and (7) foster international partnerships with multinational organisations for resource mobilisation, monitoring and evaluation of the programme to end RHD in Africa. This Addis Ababa communique has since been endorsed by African Union heads of state, and plans are underway to implement the roadmap in order to end ARF and RHD in Africa in our lifetime. PMID- 26815011 TI - Water Dynamics and Its Role in Structural Hysteresis of Dissolved Organic Matter. AB - Knowledge of structural dynamics of dissolved organic matter (DOM) is of paramount importance for understanding DOM stability and role in the fate of solubilized organic and inorganic compounds (e.g., nutrients and pollutants), either in soils or aquatic systems. In this study, fast field cycling (FFC) (1)H NMR relaxometry was applied to elucidate structural dynamics of terrestrial DOM, represented by two structurally contrasting DOM models such as Suwanee River (SRFA) and Pahokee peat (PPFA) fulvic acids purchased by the International Humic Substance Society. Measurement of NMR relaxation rate of water protons in heating cooling cycles revealed structural hysteresis in both fulvic acids. In particular, structural hysteresis was related to the delay in re-establishing water network around fulvic molecules as a result of temperature fluctuations. The experiments revealed that the structural temperature dependency and hysteresis were more pronounced in SRFA than in PPFA. This was attributed to the larger content of hydrogel-like structure in SRFA stabilized, at a larger extent, by H-bonds between carboxylic and phenolic groups. Moreover, results supported the view that terrestrial DOM consist of a hydrophobic rigid core surrounded by progressively assembling amphiphilic and polar molecules, which form an elastic structure that can mediate reactivity of the whole DOM. PMID- 26815012 TI - Corrigendum: HCRP-1 regulates cell migration and invasion via EGFR-ERK mediated up-regulation of MMP-2 with prognostic significance in human renal cell carcinoma. PMID- 26815013 TI - NDE1 and GSK3beta Associate with TRAK1 and Regulate Axonal Mitochondrial Motility: Identification of Cyclic AMP as a Novel Modulator of Axonal Mitochondrial Trafficking. AB - Mitochondria are essential for neuronal function, providing the energy required to power neurotransmission, and fulfilling many important additional roles. In neurons, mitochondria must be efficiently transported to sites, including synapses, where their functions are required. Neurons, with their highly elongated morphology, are consequently extremely sensitive to defective mitochondrial trafficking which can lead to neuronal ill-health/death. We recently demonstrated that DISC1 associates with mitochondrial trafficking complexes where it associates with the core kinesin and dynein adaptor molecule TRAK1. We now show that the DISC1 interactors NDE1 and GSK3beta also associate robustly with TRAK1 and demonstrate that NDE1 promotes retrograde axonal mitochondrial movement. GSK3beta is known to modulate axonal mitochondrial motility, although reports of its actual effect are conflicting. We show that, in our system, GSK3beta promotes anterograde mitochondrial transport. Finally, we investigated the influence of cAMP elevation upon mitochondrial motility, and found a striking increase in mitochondrial motility and retrograde movement. DISC1, NDE1, and GSK3beta are implicated as risk factors for major mental illness. Our demonstration that they function together within mitochondrial trafficking complexes suggests that defective mitochondrial transport may be a contributory disease mechanism in some cases of psychiatric disorder. PMID- 26815015 TI - A new dimeric anthraquinone from endophytic Talaromyces sp. YE3016. AB - A new unsymmetrical dimeric anthraquinone, 3-demethyl-3-(2-hydroxypropyl)-skyrin (1) was isolated from the solid-state fermentation extract of an endophytic fungal strain Talaromyces sp. YE 3016, together with five known compounds, skyrin (2), oxyskyrin (3), emodin (4), 1,3,6-trihydroxy-8-methyl-anthraquinone (5) and ergosterol (6). The structure of the new compound was elucidated on the basis of spectroscopic analysis. Compounds 1-3 exhibited moderate cytotoxic activities against MCF-7 cell line. PMID- 26815014 TI - Identification of Dormancy-Associated MicroRNAs for the Design of Osteosarcoma Targeted Dendritic Polyglycerol Nanopolyplexes. AB - The presence of dormant, microscopic cancerous lesions poses a major obstacle for the treatment of metastatic and recurrent cancers. While it is well-established that microRNAs play a major role in tumorigenesis, their involvement in tumor dormancy has yet to be fully elucidated. We established and comprehensively characterized pairs of dormant and fast-growing human osteosarcoma models. Using these pairs of mouse tumor models, we identified three novel regulators of osteosarcoma dormancy: miR-34a, miR-93, and miR-200c. This report shows that loss of these microRNAs occurs during the switch from dormant avascular into fast growing angiogenic phenotype. We validated their downregulation in patients' tumor samples compared to normal bone, making them attractive candidates for osteosarcoma therapy. Successful delivery of miRNAs is a challenge; hence, we synthesized an aminated polyglycerol dendritic nanocarrier, dPG-NH2, and designed dPG-NH2-microRNA polyplexes to target cancer. Reconstitution of these microRNAs using dPG-NH2 polyplexes into Saos-2 and MG-63 cells, which generate fast-growing osteosarcomas, reduced the levels of their target genes, MET proto-oncogene, hypoxia-inducible factor 1alpha, and moesin, critical to cancer angiogenesis and cancer cells' migration. We further demonstrate that these microRNAs attenuate the angiogenic capabilities of fast-growing osteosarcomas in vitro and in vivo. Treatment with each of these microRNAs using dPG-NH2 significantly prolonged the dormancy period of fast-growing osteosarcomas in vivo. Taken together, these findings suggest that nanocarrier-mediated delivery of microRNAs involved in osteosarcoma tumor-host interactions can induce a dormant-like state. PMID- 26815016 TI - Identification of IRX1 as a Risk Locus for Rheumatoid Factor Positivity in Rheumatoid Arthritis in a Genome-Wide Association Study. AB - OBJECTIVE: Rheumatoid factor (RF) is a well-established diagnostic and prognostic biomarker in rheumatoid arthritis (RA). However, ~20% of RA patients are negative for this anti-IgG antibody. To date, only variation at the HLA-DRB1 gene has been associated with the presence of RF. This study was undertaken to identify additional genetic variants associated with RF positivity. METHODS: A genome-wide association study (GWAS) for RF positivity was performed using an Illumina Quad610 genotyping platform. A total of 937 RF-positive and 323 RF-negative RA patients were genotyped for >550,000 single-nucleotide polymorphisms (SNPs). Association testing was performed using an allelic chi-square test implemented in Plink software. An independent cohort of 472 RF-positive and 190 RF-negative RA patients was used to validate the most significant findings. RESULTS: In the discovery stage, a SNP in the IRX1 locus on chromosome 5p15.3 (SNP rs1502644) showed a genome-wide significant association with RF positivity (P = 4.13 * 10( 8) , odds ratio [OR] 0.37 [95% confidence interval (95% CI) 0.26-0.53]). In the validation stage, the association of IRX1 with RF was replicated in an independent group of RA patients (P = 0.034, OR 0.58 [95% CI 0.35-0.97] and combined P = 1.14 * 10(-8) , OR 0.43 [95% CI 0.32-0.58]). CONCLUSION: To our knowledge, this is the first GWAS of RF positivity in RA. Variation at the IRX1 locus on chromosome 5p15.3 is associated with the presence of RF. Our findings indicate that IRX1 and HLA-DRB1 are the strongest genetic factors for RF production in RA. PMID- 26815017 TI - Gluten Introduction and the Risk of Coeliac Disease: A Position Paper by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. AB - BACKGROUND: The European Society for Paediatric Gastroenterology, Hepatology and Nutrition recommended in 2008, based on observational data, to avoid both early (<4 months) and late (>=7 months) introduction of gluten and to introduce gluten while the infant is still being breast-fed. New evidence prompted ESPGHAN to revise these recommendations. OBJECTIVE: To provide updated recommendations regarding gluten introduction in infants and the risk of developing coeliac disease (CD) during childhood. SUMMARY: The risk of inducing CD through a gluten containing diet exclusively applies to persons carrying at least one of the CD risk alleles. Because genetic risk alleles are generally not known in an infant at the time of solid food introduction, the following recommendations apply to all infants, although they are derived from studying families with first-degree relatives with CD. Although breast-feeding should be promoted for its other well established health benefits, neither any breast-feeding nor breast-feeding during gluten introduction has been shown to reduce the risk of CD. Gluten may be introduced into the infant's diet anytime between 4 and 12 completed months of age. In children at high risk for CD, earlier introduction of gluten (4 vs 6 months or 6 vs 12 months) is associated with earlier development of CD autoimmunity (defined as positive serology) and CD, but the cumulative incidence of each in later childhood is similar. Based on observational data pointing to the association between the amount of gluten intake and risk of CD, consumption of large quantities of gluten should be avoided during the first weeks after gluten introduction and during infancy. The optimal amounts of gluten to be introduced at weaning, however, have not been established. PMID- 26815018 TI - [The historical materials of stomatology in the oracle bone inscriptions of the Yin-Shang Dynasties]. AB - Some oracle bone inscriptions of the Yin-Shang Dynasties were related to the stomatology, including special terms of diseases of the mouth, tongue and teeth which were classified, and proper nouns of some special diseases. Moreover, witch doctors' exploration for the causes of oral diseases, the observation on different stages of oral diseases, and the records of oral disease treatment were also involved. All of these reflected the sprouting stage of stomatology in the Yin-Shang Dynasties in ancient China. PMID- 26815019 TI - [The characteristics of and thinking on stranguria syndrome in Zhu bing yuan hou lun (Treatise on the Pathogenesis and Manifestations of All Diseases)]. AB - The main characteristics of stranguria in the Zhu bing yuan hou lun (Treatise on the Pathogenesis and Manifestations of All Diseases) include the following: it first proposes stranguria to be discussed in different chapters, promoting the idea "heat of the bladder and kidney deficiency", which exerted profound influnce on the later generations, and discerning bloody stranguria and hematuria with different symptoms and etiology of underlying viscera; while its Daoyin method recorded being of reference value to modern clinical treatment. In addition, the etiology and pathogenesis of "heat of bladder and kidney deficiency" are referring to the five-stranguria rather than to the seven-stranguria. The lesion of part of the urolithic stranguria not nly deals with the kidney and bladder, but also involves the small intestine, stomach and spleen too. PMID- 26815020 TI - [An analysis of the medical administration pattern of the Yuan Dynasty as interpreted from the Guan yi ti ju si (Department of Official Medical Administration)]. AB - The Imperial Academy of Medicine of the Yuan Dynasty established an institution called Guan yi ti ju si (Department of Official Medical Administration). Through its central to local network, the Department carried out its medical administration throughout the nation. The responsibilities of Guan yi ti ju si included 5 aspects, viz., the selection of local medical professionals and talents; the dispatch of prison doctors; the examination and administration of local medical workers; the revision and publication of medical works and the inspection and identification of local herbs. Guan yi ti ju si played an important role in medical education and the publication of medical books which were generally considered as the work of Yi xue ti ju si (Department of General Medical Administration ). In terms of administrative pattern, there were two specialties, the government focused its work on the rational allocation and governing of local medical professionals and resources, with medical administration and medical education belonged to two separate systems, which, at the same time, supervised and controlled mutually. These noticeable features of medical administration of the Yuan Dynasty are still revealing its reference value today. PMID- 26815021 TI - [The situation of Chinese medicine practitioners in the late Qing Dynasty as viewed from the Dianshizhai Pictorial]. AB - According to the 17 pieces of news pictures closely related to Chinese medicine practitioners appeared in the Dianshizhai Pictorial, it can be seen that Chinese medicine practitioners in the 19th century can be divided into two classes, professional and non-professional practitioners. Of the 10 pieces related to professional practitioners, 8 news pictures creates "Quack doctors" as its theme, reflecting that some Chinese medicine practitioners only had poor medical skill of low quality. The other 7 pieces of news figure related to non-professional practitioners are rather complex. Some of them expresses puerpera, midwives, witch-doctors and charlatans, reflecting that the contemporary non-professional practitioners were complex, and indicating that those professional practitioners still can't meet the requirement of people in that time. PMID- 26815022 TI - [Canton Hospital and public health in Canton]. AB - Canton Hospital was not only the most influential missionary hospital in South China, but also the first one brought the concept and practice of public health to Guangzhou. In the late Qing Dynasty, it conducted free vaccination, plague treatment, health education and so on, demonstrating the importance of public health to the people. In the period of the Republic of China, it extensively cooperated with the government and social organizations in developing school health, maternal and child health, communicable disease control and epidemiological investigations to actively serve the social group. In the 1930s, its public health activities extended towards the rural areas of Guangzhou, and promoted the convergence of rural and urban medical and health services. The three-level medical system that it built provided demonstration model for the establishment of Chinese rural medical system. PMID- 26815023 TI - [A general review on women's health education of modern China]. AB - In the modern social background of strengthening the nation and its people, woman's health got the attention of Chinese and became one important part in the modernization progress of state and nation, they started the work of women's health education, publicized women's health knowledge and nursery methods through many ways and carried out midwifery education.In the name of "health", woman's body gradually be socialized and internationalized. Meanwhile, Chinese women also gradually got rid of their own discipline of the state and society, began to seek their own liberation, became one important part of China's modernization. PMID- 26815024 TI - [The apprentice education system of Chinese medicinal industry in modern Kunming]. AB - In the late Qing Dynasty, following the appearance of the Chinese medicinal materials industry trade association of Kunming, the "master agreement" as a professional regulation, also implemented, marking the beginning of the contractualization and institutionalization of apprentice education in Yunnan. The contents and implementation of the "master agreement" was organized by the Chinese medicinal materials industry trade association of Kunming and its craft union. The apprentice education in Kunming traditional Chinese medicinal industry has the following characteristics: expanding the source of talent; adepting at agricultural production of the accorded apprentice; conforming to the conditions of human manipulation of Chinese traditional medicine; being in line with the characteristics and rules of Chinese medicine skills taught by oral narration and tacit understanding; unity of the medical and pharmaceutical professionals; and non-governmental organization. Apprentice training had trained a number of medical talents, and promoted the transformation of manual workshop to industrialization in Kunming. Apprentice education had catalyzed the establishment of specialized shops selling patent medicines exclusively to separated from those running both crude drugs and patent medicines, to form a set of effective teaching system, thus exerting profound influence on later generations. PMID- 26815025 TI - [The system of health assistants in Shaanxi during the Republican period]. AB - To tackle plague, in the 21st year of the Republic of China (1932), the government of Shaanxi province, established the "Shaanxi Department of Epidemic Prevention" and set up health assistant system at the grassroots level. As the main promoter and executor of rural epidemic prevention, the health assistants played a significant role in the formation of public health knowledge propaganda, the formation of public health idea, public environmental hygiene investigation and popularization of health and epidemic prevention work. Health assistant system, as the initiation of modern Shaanxi health, marking the gradual moving forward to its modernization, exerting a positive role and, at the same time, demonstrating that the development of modern public health needs the improvement of comprehensive national strength and the simultaneous construction of political civilization. PMID- 26815026 TI - [Historical study of the research of Korean Ginseng by Japanese and Korean doctors in eighteenth century]. AB - In the eighteenth Century, Korean envoys and Japanese doctors did a lot of conversation on Korean ginseng, the content of which were arranged as books later by Japanese. Through 5 collections of those books, it is found that the contents of those conversations are focused mainly on 3 aspects, viz., the name and the quality of the Korean ginseng, processing method and cultivation conditions. Those records not only reflect the condition of Japanese doctors truly and actually getting the knowledge of Korean ginseng, but also provide precious historical data to the research on the history of Japan and Korea medical communication in the Edo period. PMID- 26815027 TI - [The origin and development of the application of ergonomics in patient safety]. AB - Human factor and ergonomics (HFE) is a discipline focusing on the studies of the relation between the safety and human behavior and system design. The application of HFE in healthcare and patient safety can be traced back to the 1950s. To date, the method and theory of HFE, including its principles and methodology, has played an important part in patient safety activities, and has gained more and more attention by the relevant health and hygienic institutions in developed countries, while its application in developing countries like China is still at the very initial stage with only a few research articles published, most of them theoretical rather than practical. PMID- 26815028 TI - [Analysis on the finalized date and first carving time of Wei sheng bao jian (The Precious Mirror of Hygiene)]. AB - The Wei sheng bao jian (The Precious Mirror of Hygiene), written by Luo Tianyi should be finished in the spring of 1283. The wrong date of 1281 was a mistake coming from Yanjian's Preface, while the complete date of 1343 was a misunderstanding on "Guiwei year of the Zhiyuan reign" in Wangyun's Preface. The hypothesis that Wei sheng bao jian was first carved in 1294 or before the Tang ye ben cao (Materia Medica for Decoctions) is also groundless. The book was probably completed, carved and distributed in the same year, or no later than 1307, even if it was not carved in the same year right after its completion. PMID- 26815029 TI - [Textual research on Huang shinuke (Huang's Obstetrics and Gynecology)]. AB - Huang shi nu ke (Huang's Obstetrics and Gynecology), a handwritten copy of the Ming Dynasty passed on by Huang Xiaoyou, Yuanyi and Huang Dongjiu, and sorted out by Huang Yanrong, was a family medical book of Huang's obstetrics and gynecology in Xin'an, being a summary of their clinical experience.There were altogether 44 chapters divided into 4 parts, including general introduction, general principle of treatment, discussions on prenatal conditions and qi acquired from the mother, and gynecological diseases in sequence, with the appendixes of pulse diagnostics for differentiating male and female, and the 10-month methods of protecting the fetus. PMID- 26815030 TI - Prediction of blood:air and fat:air partition coefficients of volatile organic compounds for the interpretation of data in breath gas analysis. AB - In this article, a database of blood:air and fat:air partition coefficients (lambda b:a and lambda f:a) is reported for estimating 1678 volatile organic compounds recently reported to appear in the volatilome of the healthy human. For this purpose, a quantitative structure-property relationship (QSPR) approach was applied and a novel method for Henry's law constants prediction developed. A random forest model based on Molecular Operating Environment 2D (MOE2D) descriptors based on 2619 literature-reported Henry's constant values was built. The calculated Henry's law constants correlate very well (R(2) test = 0.967) with the available experimental data. Blood:air and fat:air partition coefficients were calculated according to the method proposed by Poulin and Krishnan using the estimated Henry's constant values. The obtained values correlate reasonably well with the experimentally determined ones for a test set of 90 VOCs (R(2) = 0.95). The provided data aim to fill in the literature data gap and further assist the interpretation of results in studies of the human volatilome. PMID- 26815031 TI - Theoretical study of enzymatically catalyzed tautomerization of carbon acids in aqueous solution: quantum calculations and steered molecular dynamics simulations. AB - The thermodynamics and kinetics of enzymatically assisted reactions of carbon acids were studied theoretically in this work. Quantum electronic (QE) structure calculations and steered molecular dynamics (SMD) simulations were carried out. Three 3-butenal tautomerization reactions that proceed from the beta,gamma unsaturated reactant (R) to the alpha,beta-unsaturated carbon acid product (P) and occur in two elementary steps through an intermediate (I) were studied, ignoring or including the surrounding aqueous medium in the calculations. The Gibbs free energies of activation of the R ? I enolization and I ? P ketonization steps were found to decrease considerably when residues simulating enzymes were introduced into these processes. Although the processes became slightly more favorable thermodynamically when the solution was included in the simulations, they became less favorable kinetically. The results from SMD simulations of these reactions were qualitatively consistent with the values we obtained using QE as well as those found by other authors in similar studies. Our simulations also allowed us to perform a detailed study of these reactions in solution. PMID- 26815032 TI - Electronic structure, rovibrational, and dipole moment calculations for the AsCl molecule. AB - The potential energy curves of the 19 lowest-lying singlet and triplet electronic states in the (2S+1)Lambda((+/-)) representation of the AsCl molecule have been investigated using the complete active space self-consistent field (CASSCF) with multireference configuration interaction (MRCI+Q) method including single and double excitations and with the Davidson correction. The harmonic frequency omega e, the internuclear distance R e, the dipole moment, and the electronic energy with respect to the ground state T e were calculated for the electronic states considered. By using the canonical functions approach, the eigenvalue E v, the rotational constant B v, and the abscissae of the turning points R min and R max were calculated for the electronic states up to the vibrational level v = 60. The values obtained in the present work agree well with corresponding values available in the literature for several electronic states. Fifteen new electronic states were investigated here for the first time. PMID- 26815034 TI - COMPASS II: extended coverage for polymer and drug-like molecule databases. AB - The COMPASS II force field has been developed by extending the coverage of the COMPASS force field (J Phys Chem B 102(38):7338-7364, 1998) to polymer and drug like molecules found in popular databases. Using a fragmentation method to systematically construct small molecules that exhibit key functional groups found in these databases, parameters applicable to database compounds were efficiently obtained. Based on the same parameterization paradigm as used in the development of the COMPASS force field, new parameters were derived by a combination of fits to quantum mechanical data for valence parameters and experimental liquid and crystal data for nonbond parameters. To preserve the quality of the original COMPASS parameters, a quality assurance suite was used and updated to ensure that additional atom-types and parameters do not interfere with the existing ones. Validation against molecular properties, liquid and crystal densities, and enthalpies, demonstrates that the quality of COMPASS is preserved and the same quality of prediction is achieved for the additional coverage. PMID- 26815033 TI - The mechanism of the effect of U18666a on blocking the activity of 3beta hydroxysterol Delta-24-reductase (DHCR24): molecular dynamics simulation study and free energy analysis. AB - DHCR24 encodes 3beta-hydroxysterol-Delta(24)-reductase (DHCR24) catalyzing the cholesterol synthesis from desmosterol using the flavin adenine dinucleotide (FAD) as a co-factor. It is generally accepted that U18666a inhibits the reductase activity of DHCR24, but the detailed mechanism remains elusive. To explore the mechanism of the inhibitory effect of U18666a on DHCR24, we performed molecular dynamics (MD) simulations of two complexes including complexes of DHCR24-FAD-desmosterol enzymatic reactive components with and without the inhibitor U18666a. We found that the U18666a bound into the hydrophobic package near the FAD package of DHCR24. Furthermore, binding free energy of DHCR24 and desmosterol without U18666a is -54.86 kcal/mol, while the system with U18666a is 62.23 kcal/mol, suggesting that the affinity of the substrate desmosterol to DHCR24 was increased in response to the U18666a. In addition, U18666a interacts with FAD by newly forming three hydrogen bonds with Lys292, Lys367, and Gly438 of DHCR24. Finally, secondary structural analysis data obtained from the surrounding hot spots showed that U18666a induced dramatic secondary structural changes around the key residues in the interaction of DHCR24, FAD, and desmosterol. Taken together, these results for the first time demonstrate at the molecular structure level that U18666a blocks DHCR24 activity through an allosteric inhibiting mechanism, which may provide new insight into the development of a new type of cholesterol-lowering drug targeting to block the activity of DHCR24. PMID- 26815035 TI - The Defect in Autophagy Induction by Clinical Isolates of Mycobacterium Tuberculosis Is Correlated with Poor Tuberculosis Outcomes. AB - BACKGROUND: Tuberculosis (TB) represents a major global health problem. The prognosis of clinically active tuberculosis depends on the complex interactions between Mycobacterium tuberculosis (Mtb) and its host. In recent years, autophagy receives particular attention for its role in host defense against intracellular pathogens, including Mtb. In present study, we aim to investigate the relationship of autophagy induction by clinical isolates of Mtb with the clinical outcomes in patients with TB. METHODOLOGY/PRINCIPAL FINDINGS: We collected 185 clinical isolates of Mtb, and determined the effect of these Mtb isolates on autophagy induction in macrophages. It was found that most of clinical isolates of Mtb were able to induce autophagosome formation in macrophages, however, the autophagy-inducing ability varied significantly among different isolates. Of importance, our results revealed that patients infected by Mtb with poor autophagy-inducing ability displayed more severe radiographic extent of disease (p<0.001), and were more likely to have unfavorable treatment outcomes (p<0.001). No significant association was observed between the extent of Mtb-induced autophagy with some socio-demographic characteristics (such as gender, age and tobacco consumption), and some laboratory tests (such as hemoglobin, leukocyte count and erythrocyte sedimentation rate). Furthermore, results from logistic regression analysis demonstrated that the defect in autophagy induction by clinical isolates of Mtb was an independent risk factor for far-advanced radiographic disease (aOR 4.710 [1.93-11.50]) and unfavorable treatment outcomes (aOR 8.309 [2.22-28.97]) in TB. CONCLUSION/SIGNIFICANCE: These data indicated that the defect in autophagy induction by Mtb isolates increased the risk of poor clinical outcomes in TB patients, and detection of clinical isolates-induced autophagosome formation might help evaluate the TB outcomes. PMID- 26815036 TI - Efficacy of oral afoxolaner plus milbemycin oxime chewables against induced infestations with Dermacentor reticulatus in dogs. AB - The efficacy of afoxolaner plus milbemycin oxime (AFX + MO) combination chewables (NexGard Spectra(r), Merial) and AFX single-entity chewables (NexGard(r), Merial) against induced infestations with Dermacentor reticulatus ticks was evaluated in dogs. Thirty dogs were assigned to blocks of three animals each based on pre allocation tick counts and were randomly allocated to one of three groups: untreated (control), treated with a combination of AFX + MO chewables to be as close as possible to the minimum effective dose of AFX + MO (2.5 + 0.5 mg per kg body weight), and treated with a combination of NexGard(r) chewables to be as close as possible to the minimum effective dose of AFX (2.5 mg per kg body weight). Treatments were administered orally once on day 0. Starting 2 days before treatment administration, each dog was infested with approximately 50 ticks weekly for six consecutive weeks. Live ticks were counted at ~48 h post treatment (removal count) and at ~48 h (in situ counts) and ~72 h (removal counts) following each post-treatment infestation. Treatment with both AFX + MO and NexGard(r) chewables rapidly eliminated the existing tick infestations (100 % efficacy) within 2 days following treatment administration. Weekly re infestations were controlled for a minimum of 5 weeks with the efficacy ranging from 92.2 to 99.7 % based on ~48 h post-treatment in situ counts and between 99.0 and 100 % based on ~72 h post-treatment removal counts (p < 0.0001 at each occasion). This study demonstrated a high efficacy of both AFX + MO chewable and NexGard(r) chewable treatments against infestations of dogs with D. reticulatus ticks for at least 5 weeks. In addition, this study indicated no interference between the two compounds with respect to the acaricidal activity provided by AFX. PMID- 26815037 TI - Description and molecular characterization of a new Leucocytozoon parasite (Haemosporida: Leucocytozoidae), Leucocytozoon californicus sp. nov., found in American kestrels (Falco sparverius sparverius). AB - Diurnal raptors in the order Accipitriformes are commonly parasitized with Leucocytozoon spp., and the prevalence and intensity of parasitemia are often high. However, for raptors in Falconiformes, several studies have reported relatively low prevalences (1 % or less) of Leucocytozoon spp. Leucocytozoon parasite pathogenicity has been documented in falcons, but little is known about the diversity, prevalence, and phylogenetic relationships among Leucocytozoon species in these predatory birds. The research reported here combines molecular and microscopic techniques to identify and describe Leucocytozoon parasites in Falco sparverius sparverius, the American kestrel, and place those parasites into a phylogenetic context with leucocytozoids previously found in other diurnal raptors (Accipitriformes), owls (Strigiformes), passerines (Passeriformes), and other bird species. Of 35 American kestrels sampled, 13 birds (37.1 %) were found by PCR to harbor the DNA lineage of a novel species, Leucocytozoon californicus. No other Leucocytozoon parasite lineages were identified in our sample. Phylogenetic analysis revealed that this parasite clusters more closely with leucocytozoids found in owls and passerines than it does with leucocytozoids found in birds of the genera Buteo and Accipiter of the order Accipitriformes. This is the first described species of Leucocytozoon that parasitizes diurnal raptors in which gametocytes develop exclusively in roundish host blood cells. It is also the first Leucocytozoon species that is described and named in birds of the Falconiformes, in which, for unclear reasons, leucocytozoids are significantly less prevalent and less diverse than in raptors with a similar behavioral ecology belonging to the Accipitriformes. PMID- 26815038 TI - Cryptosporidium infections of ring-necked pheasants (Phasianus colchicus) from an intensive artificial breeding programme in the Czech Republic. AB - From July to November 2012, preliminary coprological examinations were carried out on 85 pooled faecal samples of different aged ring-necked pheasants (Phasianus colchicus) (hatches from May until July) from an intensive artificial breeding programme in the Czech Republic. Cryptosporidium oocysts were detected in 12 samples (14.1 %) of ages >12 weeks (August-September). These results were supported by findings of Cryptosporidium baileyi and Cryptosporidium meleagridis oocysts in intestinal, or cloacal contents, and/or the bursa of Fabricius in 9 from 36 examined dead pheasants (prevalence 25 %). We describe in detail the various age groups of pheasants after hatching and present graphically the overall results of coprological examinations, showing pathways of infection of C. baileyi and C. meleagridis during the full rearing seasons of 2013 and 2014. We found very similar mean proportions of Cryptosporidium-positive samples over the entire 2013 period in pheasantry (173 pooled samples tested, 25 positive, 14.5 %) and 2014 (238 samples tested, 43 positive, 18.1 %). All tests were verified as being Cryptosporidium positive in 9 from 219 (prevalence 4.1 %) and 4 from 168 (prevalence 2.4 %) post-mortem examinations. Significantly, C. baileyi was found more frequently in faeces, with positivities ranging from 11.1 to 100 % (4->16 week-old pheasants). Oocysts of C. meleagridis were detected at ages 6->15 weeks ranging from 7.1 to 100 % in faeces during the rearing seasons. The burdens of C. baileyi (7 of 14 and 10 of 16) and C. meleagridis (5 of 14 and 7 of 16) for each year, in monitored brooder houses, flight pens and spread across all open areas were recorded. Oocysts of C. baileyi and C. meleagridis obtained from this study, and Cryptosporidium galli (obtained in another aviary from 36-week-old pheasants), were sequenced, and we characterized the highly variable 60-kDa glycoprotein gene of C. meleagridis. These results highlight the real risk of transmission of Cryptosporidium to susceptible wild birds and other potential hosts after termination of rearing and release. PMID- 26815039 TI - Association between Daily Hospital Outpatient Visits for Accidents and Daily Ambient Air Temperatures in an Industrial City. AB - An accident is an unwanted hazard to a person. However, accidents occur. In this work, we search for correlations between daily accident rates and environmental factors. To study daily hospital outpatients who were admitted for accidents during a 5-year period, 2007-2011, we analyzed data regarding 168,366 outpatients using univariate regression models; we also used multivariable regression models to account for confounding factors. Our analysis indicates that the number of male outpatients admitted for accidents was approximately 1.31 to 1.47 times the number of female outpatients (P < 0.0001). Of the 12 parameters (regarding air pollution and meteorology) considered, only daily temperature exhibited consistent and significant correlations with the daily number of hospital outpatient visits for accidents throughout the 5-year analysis period. The univariate regression models indicate that older people (greater than 66 years old) had the fewest accidents per 1-degree increase in temperature, followed by young people (0-15 years old). Middle-aged people (16-65 years old) were the group of outpatients that were more prone to accidents, with an increase in accident rates of 0.8-1.2 accidents per degree increase in temperature. The multivariable regression models also reveal that the temperature variation was the dominant factor in determining the daily number of outpatient visits for accidents. Our further multivariable model analysis of temperature with respect to air pollution variables show that, through the increases in emissions and concentrations of CO, photochemical O3 production and NO2 loss in the ambient air, increases in vehicular emissions are associated with increases in temperatures. As such, increases in hospital visits for accidents are related to vehicular emissions and usage. This finding is consistent with clinical experience which shows about 60% to 80% of accidents are related to traffic, followed by accidents occurred in work place. PMID- 26815040 TI - Cloning, Expression, and Purification of Histidine-Tagged Escherichia coli Dihydrodipicolinate Reductase. AB - The enzyme dihydrodipicolinate reductase (DHDPR) is a component of the lysine biosynthetic pathway in bacteria and higher plants. DHDPR catalyzes the NAD(P)H dependent reduction of 2,3-dihydrodipicolinate to the cyclic imine L-2,3,4,5, tetrahydropicolinic acid. The dapB gene that encodes dihydrodipicolinate reductase has previously been cloned, but the expression of the enzyme is low and the purification is time consuming. Therefore the E. coli dapB gene was cloned into the pET16b vector to improve the protein expression and simplify the purification. The dapB gene sequence was utilized to design forward and reverse oligonucleotide primers that were used to PCR the gene from Escherichia coli genomic DNA. The primers were designed with NdeI or BamHI restriction sites on the 5'and 3' terminus respectively. The PCR product was sequenced to confirm the identity of dapB. The gene was cloned into the expression vector pET16b through NdeI and BamHI restriction endonuclease sites. The resulting plasmid containing dapB was transformed into the bacterial strain BL21 (DE3). The transformed cells were utilized to grow and express the histidine-tagged reductase and the protein was purified using Ni-NTA affinity chromatography. SDS/PAGE gel analysis has shown that the protein was 95% pure and has approximate subunit molecular weight of 28 kDa. The protein purification is completed in one day and 3 liters of culture produced approximately 40-50 mgs of protein, an improvement on the previous protein expression and multistep purification. PMID- 26815042 TI - Screening for osteoporosis in Chinese post-menopausal women: a health economic modelling study. AB - Screening and appropriate treatment for osteoporosis has been proven to be cost effective in many populations; however, it is not clear in the Chinese population. Simulations using a validated health economics model suggest that screening for osteoporosis in Chinese women is cost-effective and may even be cost-saving in Chinese post-menopausal women. INTRODUCTION: This study aimed at determining the cost-effectiveness of osteoporosis screening strategies in post menopausal Chinese women. METHODS: A validated state-transition microsimulation model with a lifetime horizon was used to evaluate the cost-effectiveness of different screening strategies with treatment of alendronate compared with current osteoporosis management in China. Osteoporosis screening strategies assessed were (1) universal screening with dual-energy X-ray absorptiometry (DXA) alone; (2) Osteoporosis Self-Assessment Tool for Asians (OSTA) + DXA; and (3) quantitative ultrasound (QUS) + DXA with rescreening at 2, 5 or 10-year intervals for patients screened negative by DXA. The study was performed from the Chinese healthcare payer's perspective. All model inputs were retrieved from publically available literature. Uncertainties were addressed by one-way and probabilistic sensitivity analysis. RESULTS: Screening strategies all improved clinical outcomes at increased costs, and each were cost-effective compared with no screening in women aged 55 years given the Chinese willingness-to-pay threshold of USD 20,000 per quality-adjusted life year (QALY) gained. Pre-screening with QUS and subsequent DXA screening if the QUS T-score <= -0.5 with a 2-year rescreening interval was the most cost-effective strategy with the highest probability of being cost-effective across all non-dominated strategies. Screening strategies were cost-saving if screenings were initiated from age 65 years. One-way sensitivity analyses indicated that the results were robust. CONCLUSIONS: Pre-screening with QUS with subsequent DXA screening if the QUS T score <= -0.5 with a 2-year rescreening interval in the Chinese women starting at age 55 is the most cost-effective. In addition, screening and treatment strategies are cost-saving if the screening initiation age is greater than 65 years. PMID- 26815043 TI - Bioactive polyphenol interactions with beta amyloid: a comparison of binding modelling, effects on fibril and aggregate formation and neuroprotective capacity. AB - In this study we compared the effects of a diverse set of natural polyphenolics ligands on in silico interactive modelling, in vitro anti-aggregative properties and neuronal toxicity of beta amyloid. The beta amyloid-binding characteristics of optimised structural conformations of polyphenols with ascribed neuroprotective actions including punicalagin, myricetin, luteolin and honokiol were determined in silico. Thioflavin T and transmission electron microscopy were used to assess in vitro inhibitory effects of these polyphenols on Abeta1-42 fibril and aggregation formation. Phaeochromocytoma (PC12) cells were exposed to Abeta1-42, alone and in combination with test concentrations of each polyphenol (100 MUM) and viability measured using MTT assay. Abeta1-42 evoked a concentration-dependent loss of cell viability in PC12 cells, in which all four polyphenols demonstrated significant inhibition of neurotoxicity. While all compounds variably altered the morphology of Abeta aggregation, the flavonoids luteolin and myricetin and the lignan honokiol all bound in a similar hydrophobic region of the amyloid pentamer and exerted the most pronounced inhibition of Abeta1-42 aggregation. Each of the polyphenols demonstrated neuroprotective effects in PC12 cells exposed to Abeta1-42, including punicalagin. These findings highlight some structure-activity insights that can be gleaned into the anti aggregatory properties of bioactive polyphenols based on modelling of their binding to beta-amyloid, but also serve to highlight the more general cellular neuroprotective nature of such compounds. PMID- 26815041 TI - Associations between vitamin D receptor gene polymorphisms and ankylosing spondylitis in Chinese Han population: a case-control study. AB - We assessed whether the vitamin D receptor gene polymorphisms (FokI, BsmI, ApaI, and TaqI) were associated with ankylosing spondylitis (AS) in a Chinese Han population. The TaqI polymorphism G allele was a risk factor in AS susceptibility. INTRODUCTION: Previous studies have found that serum vitamin D levels are declined in patients with AS. The present study aims to evaluate the role of vitamin D receptor (VDR) gene polymorphisms in AS susceptibility in a Chinese Han population. METHODS: Four single nucleotide polymorphisms (SNPs) in the VDR gene (FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236)) were genotyped by the improved multiplex ligase detection reaction (iMLDR) method in 620 AS patients and 620 geographically and ethnically matched healthy controls. Haplotypes were constructed after linkage disequilibrium (LD) analysis. RESULTS: Statistically significant difference was only found in the TaqI polymorphism between AS patients and controls. The TaqI polymorphism G allele was higher in AS group than that in controls (OR [95 % CI] = 1.624 [1.122 2.352], chi (2) = 6.705, P = 0.006). Linkage disequilibrium has been detected in TaqI and BsmI polymorphisms (D' = 0.87, r (2) = 0.70). Two novel haplotypes (H1: AC and H2: GT) were significantly associated with the risk of AS, and they play protective and risk roles in AS morbidity, respectively. CONCLUSIONS: The VDR gene TaqI polymorphism G allele may be a risk factor in AS susceptibility. PMID- 26815044 TI - Tyrosinase inhibitors: a patent review (2011-2015). AB - INTRODUCTION: Tyrosinase is responsible for melanin production. The overproduction of melanin causes many skin disorders. The inhibition of tyrosinase activity would appear to be the most rational and explicit way of overcoming these issues. AREAS COVERED: Thirty eight patents on synthetic tyrosinase inhibitors issued since 2011 were reviewed. Inhibitors were categorized by chemical structure and assigned to eight classes. Information on potent inhibitors in each class is provided. EXPERT OPINION: Many tyrosinase inhibitors of natural or synthetic origin have been identified, but very few are qualified for clinical use. Thus medicinal scientists have to work more on the identification of potent and safe tyrosinase inhibitors. Various chemical scaffolds have been explored. Among them, the scaffolds such as resorcinol, biaryl, imidazolethione, beta-phenyl-alpha,beta-unsaturated carbonyl, and some double strand oligonucleotides have shown high tyrosinase inhibition, low toxicities, and great potencies. Detail structure activity relationship studies of these potential scaffolds could provide directions for a new and potent tyrosinase inhibitors. Furthermore new trends, such as the use of synergistic phenomena, salt formation, drug repositioning and designing of multi-targeted tyrosinase inhibitors could expand search areas for much improved tyrosinase inhibitors. PMID- 26815045 TI - A systematic review of central sleep apnea in adult patients with chronic kidney disease. AB - BACKGROUND: Obstructive sleep apnea has been widely studied in patients with chronic renal insufficiency; however only a limited number of studies have reviewed the association between central sleep apnea (CSA) and chronic kidney disease (CKD). The objectives of this systematic review were to assess the prevalence of CSA in and its association with CKD in adult patients and to determine if inclusion of the central hypopnea index affected the reported rates for the prevalence of CSA in CKD. METHODS: Medline, Web of Science, Google Scholar, Scopus, and Cochrane Library were searched through October 2015 without any language limitations. RESULTS: Of 188 articles searched, 8 articles met our study inclusion criteria. Of a cumulative total of 313 patients with CKD undergoing sleep study, a total of 30 patients were diagnosed with central sleep apnea. Three studies had patients with coexistent congestive heart failure, six studies included some patients on dialysis and at least 3 studies included central hypopneas while calculating central sleep apnea index. CONCLUSION: The aggregate point prevalence of CSA in CKD is 9.6 %, although the estimated range is highly variable between 0 and 75 %. Limited evidence suggested that even after adjustment for cardiovascular comorbidities, CKD is independently associated with CSA. It is unknown if patients on dialysis are at increased risk compared to patients without end-stage renal disease. Standardization of polysomnographic criteria used to define CSA and sleep disordered breathing (SDB) as well as inclusion of central hypopneas in the overall CSA index will limit the heterogeneity and allow better estimation of the prevalence of CSA in patients with CKD. PMID- 26815046 TI - A tribute to Mats Gyllenberg, on the occasion of his 60th birthday. PMID- 26815047 TI - Time for a Comprehensive Ultrasound- Enhanced Trauma Management. PMID- 26815049 TI - Focused Echocardiography in Life Support: The Subcostal Window : What the Surgeon Should Know for Critical Care Applications. AB - CONTEXT: Focused echocardiography evaluation in life support (FEEL) for emergency and critical caremedicine is an innovative approach to introducing limited-in scope echocardiography in a timely fashion into periresuscitation care. FEEL is an advanced life support-conformed concept and a simple procedure that can be readily used in shock roomor pre-hospital scenarios as an extension of focused abdominal sonography for trauma (FAST). The subcostal window plays a pivotal role in this context, because it can easilybe applied inthesupine position, and is usually better than other windows in patients with mechanical ventilation or during resuscitation maneuvers. Most information can be obtained at a glance. AIM: As the FAST exam was not developed for implementation in resuscitation or cardiac arrest procedures, herewedescribe an accurate and easymethod that allows non-cardiologists to add FEEL to the FAST exam. As a result, it conforms to actual resuscitation guidelines. To perform the FEEL procedure and the subcostal window, a specific training seems to bemandatory. The aim of this paper is to set special emphasis on the use of the subcostal window. PMID- 26815048 TI - Prehospital and Emergency Department Ultrasound in Blunt Abdominal Trauma. AB - Blunt abdominal trauma is a challenging aspect of trauma management. Early detection has a major impact on patient outcome. In contrast to physical examination, computed tomography is known to be a sensitive and specific test for blunt abdominal injuries. However, it is time-consuming and thus contraindicated in hemodynamically unstable patients. Therefore, focused assessment with sonography for trauma (FAST) offers a fast and easily applicable screening method to identify patients for urgent laparotomy without any further diagnostics. FAST detects, with high sensitivity, intraperitoneal fluid that accumulates in dependent areas indicating blunt abdominal trauma. FAST has been established as a gold standard early screening method for blunt abdominal trauma when performing trauma management in the emergency department (ED) based on the Advanced Trauma Life Support((r)) algorithm. The development of hand-held ultrasound devices facilitated the introduction of FAST into prehospital trauma management. It was demonstrated that prehospital FAST (p-FAST) can be performed with high sensitivity and specificity, and can lead to significant changes in prehospital trauma therapy and management. Standardized training with both theoretical and hands-on modules is mandatory in order to gain the skills required to perform FAST or p-FAST well. PMID- 26815050 TI - Resuscitative Long-Bone Sonography for the Clinician: Usefulness and Pitfalls of Focused Clinical Ultrasound to Detect Long-Bone Fractures During Trauma Resuscitation. AB - Bone has one of the highest acoustic densities (AD) in the human body. Traditionally, bone has been considered to be a hindrance to the use of ultrasound (US), as US waves are reflected by the dense matrix and obscure underlying structures. The intense wave reflection, however, can clearly illustrate the cortical bony anatomy of long bones, making cortical disruption obvious. Ultrasound can be used at the bedside concurrently with the overall trauma resuscitation, and may potentially limit the patient's and treating team's exposure to ionizing radiation, corroborate clinical findings, and augment procedural success. The extended focused assessment with sonography for trauma (EFAST) is an essential tool in the resuscitation of severe torso trauma, frequently demonstrating intra- pericardial and intra-peritoneal fluid, inferring hemo/pneumothoraces, and demonstrating cardiac function. Although it is typically considered as a diagnosis of exclusion, multiple long-bone fractures may be a source of shock and can be quickly confirmed at the bedside with EFAST. Further, the early detection of long-bone fractures can also aid in the early stabilization of severely injured patients. Sonographic evaluation for long-bone fractures may be particularly useful in austere environments where other imaging modalities are limited, such as in the battlefield, developing world, and space. While prospective study has been limited, selected series have demonstrated high accuracy among both physician and para-medical clinicians in detecting long-bone fractures. Pitfalls in this technique include reduced accuracy with the small bones of the hands and feet, as well as great reliance on user experience. PMID- 26815051 TI - Healing of Blunt Liver Injury After Non-Operative Management: Role of Ultrasonography Follow-Up. AB - BACKGROUND: Non-operative management of patients with blunt liver trauma has become the standard of care. Usually after initial computed tomography (CT) evaluation and a short-term intra-hospital instrumental and clinical monitoring, no other imaging assessment is routinely requested. A restriction of physical activities for a few (unfixed number of) months is the most common recommendation. A few studies investigated the re-establishment of normal hepatic parenchymal architecture, but there is no evidence of the correct length of time for a certain resumption to normal life. To understand the progression of traumatic liver damage and the time course of healing, and to indicate the correct spontaneous recovery time, a long-term sonographic followup was done. METHODS: Forty-four patients with blunt non-operatively managed hepatic injury were selected by a retrospective review of a prospectively collected database. At admission, in accordance with the American Association for the Surgery of Trauma (AAST), all lesions were evaluated by CT and graded by the Organ Injury Scale (OIS). The progression of liver repair was followed by ultrasonographic (US) controls on days 3, 5, 10, 15, 30, and 60, and monthly up to a complete clinical recovery and sonographic disappearance of lesions. RESULTS: One OIS grade I, 20 grade II, 13 grade III, eight grade IV, and two grade V hepatic injuries were included in the study. Forty patients were monitored until liver normalization by 218 US examinations. The median time for liver repair in OIS grades II, III, IV, and V was 30, 63, 62, and 118 days, respectively, and 75% of the patients recovered in 60, 80, and 98 days in the II, III, and IV classes, respectively. CONCLUSION: In our experience, a long time variability for spontaneous liver repair after blunt trauma and non-operative treatment was found, but a parenchymal US normalization was evidenced in a median time shorter than that usually reported in the literature. PMID- 26815052 TI - Long-Term Health-Related Quality of Life in Major Pediatric Trauma: A Pilot Study. AB - BACKGROUND: Major trauma is the leading cause of mortality and morbidity in children of developed countries. Little research has been done about the health related quality of life (HRQL) in these children. The aim of the current research is to describe the HRQL of children in the long term after major trauma and to compare it with healthy peers. METHODS: A prospective cohort study of severely injured children (ISS >= 16, age < 16 years) who survived the trauma and were admitted to the emergency department of a Dutch level 1 trauma center in 1999 and 2000 (n = 40) was conducted. Between 6 and 8 years after trauma (mean 7.3, SD 0.7 years), outcome was assessed by the Pediatric Quality of Life Inventory (PedsQL 4.0), the EuroQol 5D (EQ-5D), and the EuroQol Visual Analogue Scale (EQ-VAS). RESULTS: The mean age at the time of the accident was 8.9 years (SD 4.6 years), the mean ISS was 24.9 (SD 11.1), and 25 (63%) cases were male; 28 out of 40 patients were followed up. The mean score on the PedsQL was 81.2 and this did not differ significantly from the norm value. On the EQ-5D, more health problems were reported than in a healthy reference population. The mean EQ-VAS score was 79.4 and was significantly lower than in healthy peers. The lowest scores on the PedsQL and the EQ-VAS were seen in teenagers and in respondents with spinal cord and/or severe cerebral injury. CONCLUSION: The results on HRQL in children in the long term after major trauma are inconclusive. Special attention should be given to teenagers with spinal cord or severe cerebral injury who reported the lowest HRQL. PMID- 26815053 TI - Independent Predictors of Treatment Modality for Penetrating Colon Injury. AB - BACKGROUND AND AIMS: We aimed to evaluate the independent factors of the treatment of penetrating colon injuries in a teaching and research hospital in light of some of the most commonly cited considerations affecting the decision as to whether to perform primary repair or divert. METHODS: Hospital records of patients between January 2004 and January 2007 were reviewed retrospectively. Fifty-seven patients were included and divided into two groups. Group A consisted of patients (n = 43) who had primary repair or resection and anastomosis, and Group B consisted of patients (n = 14) who had diverting colostomy. The degree of fecal contamination was assessed by reviewing the detailed operative dictation. The type of colon injury, as determined from the colon injury scale (CIS) of the American Association for the Surgery of Trauma (AAST), and the penetrating abdominal trauma index (PATI) were recorded. RESULTS: Age, sex, presence of shock on admission, location of the injury, and colon-related or non-colonrelated complications between the two groups were not significant. Stab or gunshot injury, operation time, degree of fecal contamination (grade 1/2/3), transfusion, PATI score, hospital stay, and associated organ injury were significantly different in the two groups (p < 0.05). CONCLUSION: Despite the fact that CIS, fecal contamination, transfusion, PATI and delayed operation affect the decision about the procedure, primary repair can be performed safely on patients with penetrating colon injuries. PMID- 26815054 TI - Optimizing Outcomes in the Jehovah's Witness Following Trauma: Special Management Concerns for a Unique Population. AB - BACKGROUND: The objective of this study was to describe the management of the Jehovah's Witness (JW) in an intensely active level I trauma center and review the modern therapeutic options available for the trauma care of these patients. STUDY DESIGN: A retrospective review of injured JWs admitted to a busy trauma center over a 13-year period was conducted. RESULTS: Over the study period, 143 JWs were identified. Among these, 15.4% (22/143) overall and 32.3% (10/31) requiring surgical intensive care unit (SICU) admission accepted transfusion. Overall, 56.6% of JWs (81/143) required operation and 21.7% (31/143) were admitted to the SICU with a complication rate of 4.2% (6/143) and a mortality of 1.4% (2/143). One patient of the 31 patients that were admitted to the SICU received 10 ml of blood with subsequent discontinuation of the transfusion and was excluded from analysis. Of the 30 JWs admitted to the SICU, 20 (66.7%) did not receive transfusion and demonstrated mean admission and nadir hemoglobin (Hb) levels of 12.7 (+/-2.5) and 9.1 (+/-3.0) mg/dl, respectively. Ten patients accepted transfusion. This group had longer mean SICU stays (23.3 vs. 5.5 days) but similar mortality (10%, 1/10 vs. 5%, 1/20) compared to non-transfused counterparts. Only one complication (1/20, 5%) was observed in the JWs who were not transfused, compared to a 40% (4/10) complication rate in those accepting transfusion. CONCLUSION: Although our experience was limited, we found no significant difference in the mortality or morbidity between JW patients who received or abstained from transfusion following major trauma. We should keep in mind that the population was small, in order to extract safe conclusions regarding whether we should transfuse or not transfuse trauma patients. We can, however, see interesting insights on the value of trauma resuscitation. PMID- 26815055 TI - A New Injectable Brushite Cement: First Results in Distal Radius and Proximal Tibia Fractures. AB - OBJECTIVE: The restoration of metaphyseal defects remains a challenge for the treating surgeon. Although injectable brushite cements may help to refill bone defects stabilized with internal fixation, human data remains unavailable. The main goal of this prospective multicenter study was to observe the performance of this material in a clinical setting. PATIENTS AND METHODS: The study conducted in seven trauma units included closed metaphyseal distal radius and proximal tibia fractures with bone defects, stabilized with internal fixation and subsequent filling with brushite cement. At 6- and 12-month follow-ups, patient satisfaction (visual analog scale [VAS]) was recorded, as well as complications. RESULTS: Thirty-eight proximal tibia fractures and 37 patients with distal radius fractures were included. Overall patient satisfaction with the treatment was high (mean VAS = 92 and 91 for proximal tibia and distal radius, respectively), despite the loss of reduction being described in 11% of proximal tibia and 24% of distal radius fractures; the majority of them included severe fracture types. Radiological evaluation showed postoperative cement leakage in 20 cases, where the majority occurred at the distal radius (n = 15). In 13 distal radius fractures, the leakage was resorbed by the final examination. CONCLUSION: The tested material showed good outcome in the majority of patients and adequate resorption characteristics, even in the case of extravasation. Stable internal fixation, sufficient bone quality, and no contact between the cement and joint are essential requirements for chronOS Inject, which can be considered as an alternative to existing augmentation materials. PMID- 26815056 TI - Minimal Invasive Fixation of Hamate Hook Fractures Through a Dorsal Percutaneous Approach Using a Mini Compression Screw: An Experimental Feasibility Study. AB - PURPOSE: Isolated fractures of the hamate hook can be treated by conservative or surgical means. Because nonoperative treatment is associated with high nonunion rates, surgical treatment with open reduction and internal fixation through a palmar approach is often preferred. The aim of this study was to refine surgical treatment of hamate hook fractures using a cannulated mini compression screw through a dorsal percutaneous approach. METHODS: Artificial fractures of the hamate hook were created in five male cadaver hands under fluoroscopy. Using an ulnar approach, the hamate hook was fractured at the base (n = 3) and middle third (n = 2) of the hook using an osteotome. Each fracture was visualized by X ray and computed tomography. Under fluoroscopy, the fracture was stabilized with a 1.1 mm K wire through a dorsal percutaneous approach which guided the introduction of a 3 mm diameter cannulated mini compression screw. The screw position was then controlled by X-ray and computed tomography. RESULTS: Percutaneous fixation of the fractured hook through the dorsal approach was achieved in all cases. Regardless of the fracture location, all fragments were adapted into anatomically correct positions. No displacement or disruption of the cortex of the hook was observed with central screw positioning. CONCLUSION: Minimal invasive repair of isolated hamate hook fractures through a dorsal percutaneous approach is feasible. The special properties of the cannulated mini compression screw allow optimal screw positioning and stable fixation without risk of diplacement or disruption of the hook fragment. PMID- 26815057 TI - Low probability of Significant Intra-Abdominal Injury in Stable Patients with Abdominal ''Seat Belt Sign''. AB - STUDY OBJECTIVE: Our aim was to determine the diagnostic significance of the association between the abdominal skin bruise from a seat belt and the presence of intraabdominal injury. METHODS: This was an observational analysis of prospectively collected data on 45 patients who presented with an abdominal seat belt sign to a level 1 trauma center following a motor vehicle accident between July 2004 and December 2007. The patients were evaluated by computed tomography (CT) scans or ultrasonography (FAST), depending on their hemodynamic stability. They were then hospitalized for treatment or observation. RESULTS: Forty-five patients [23 males (51.1%) and 22 females (48.9%)], with a mean age of 32.2 years (range 16-80 years), fulfilled entry criteria and were enrolled. Of these, 44 (97.8%) underwent CT, and one (2.2%) underwent FAST due to hemodynamic instability. two patients (4.4%) had intraabdominal injuries: one required surgery for bowel injury, and the other had a minor liver laceration, which was managed expectantly. Sixteen patients (35.5%) had concomitant injuries. The length of hospital stay ranged from 1-23 days (median 2.2 days). CONCLUSIONS: Despite the widely accepted view that patients with an abdominal seat belt sign are more likely to have serious intraabdominal injuries, the results of our investigation showed no such association in a group of hemodynamically stable patients. PMID- 26815058 TI - Is nonoperative treatment still indicated for Jones fracture? AB - INTRODUCTION: The issue of whether to treat Jones fracture surgically or nonsurgically is still controversial. In our institution, most acute Jones fractures are treated conservatively. OBJECTIVES: This study assessed the functional outcomes of patients with acute Jones fractures that were treated conservatively by means of radiographic assessment, a physician-based scoring system and patient-based questionnaires. METHODOLOGY: In this study, 25 patients with Jones fracture treated in our institution between January 2002 to December 2006, were retrospectively reviewed. Injuries were classified according to Jones' original description and the Torg classification. A simple patient satisfaction questionnaire was completed. Radiographic assessment of fracture union was recorded. Outcome instruments used were (a) the American Orthopaedic Foot and Ankle Society (AOFAS) clinical rating systemand (b) the American Academy of Orthopaedic Surgeons (AAOS) foot and ankle outcome questionnaire. RESULTS: Of the 25 patients reviewed, 60% were very satisfied with the outcome, 28% were satisfied, 8% were fairly satisfied, and 4% were very dissatisfied. Based on radiographic and clinical assessments, one patient had delayed union and was treated surgically. The functional outcome scores were: mean AOFAS clinical rating score of 95.6 +/- 7.7% (P < 0.005), mean AAOS foot and ankle score of 97.0 +/- 4.4% (P < 0.005) and mean AAOS shoe comfort score of 90.2 +/- 19.6% (P < 0.005). CONCLUSIONS: Acute Jones fracture can be treated conservatively with good functional outcome. PMID- 26815059 TI - Median Nerve Injury Due to High-Pressure Water Jet Injection: A Case Report and Review of Literature. AB - High-pressure injuries that occur accidentally are potentially destructive injuries that often affect the nondominant hands of young men. A variety of products such as paint, gasoline, grease, fuel oil, cement, thinner and solvents have been reported as destructive agents. High-pressure water jet injection injuries to soft tissues have rarely been reported. In this study, we present the first case of median nerve injury due to high-pressure water jet injection by a water spray gun. PMID- 26815060 TI - Thoracoscopic and Laparoscopic Esophagectomy in a Case of Spontaneous Rupture of the Esophagus (Boerhaave's Syndrome). AB - Spontaneous barogenic rupture of the esophagus is a rare disease with high morbidity and mortality. Many therapeutic options are available. Esophagectomy is indicated when a large rupture is found with huge mediastinal contamination. Here, we describe a minimal invasive esophagectomy procedure for an esophageal barogenic rupture. A thoracoscopic esophagectomy was performed with the patient in a prone position. After a laparoscopic gastric tubulization, a cervical esopagho-gastro anastomosis was performed with a retro-sternal passage of the stomach in order to avoid the heavily contaminated posterior mediastinum. The postoperative outcome was almost uneventful. This minimal-invasive approach allowed direct optimal visualization of the esophageal laceration and a thorough mediastinal cleansing, thereby avoiding any septic complications, which are the major concern in this particular clinical procedure. In our case, the esophagectomywas mandatory because of the large laceration and massive mediastinal contamination. The minimal invasive thoracoscopic and laparoscopic esophagectomy approach is feasible even in an emergency setting. This is the first report of this procedure being used in a high-risk patient with Boerhaave's syndrome. PMID- 26815061 TI - Endovascular Treatment of an Axillary Pseudoaneurysm Following a Traumatic Shoulder Dislocation. AB - A pseudoaneurysm following a shoulder dislocation is considered rare. We report here a case of an 82-yearold man who suffered from vascular and neurological injury due to an axillary pseudoaneurysm following anterior dislocation of the left shoulder. An emerging swelling in the shoulder region was caused by a hematoma and a slowly bleeding pseudoaneurysm in combination with reactive swelling of the soft tissues. Neurological damage occurred due to local compression. A minimally invasive technique was used to treat the pseudoaneurysm. Embolization was initially attempted, but this treatment failed. A stent was subsequently inserted to eliminate the axillary pseudoaneurysm from the circulation. Early imaging and an aggressive endovascular treatment should be considered in all patients suffering from an axillary artery (pseudo)aneurysm. PMID- 26815062 TI - Letter to the Editor. PMID- 26815063 TI - Comment by the author. PMID- 26815064 TI - hnuSABR: Photochemical Dose-Response Bead Screening in Droplets. AB - With the potential for each droplet to act as a unique reaction vessel, droplet microfluidics is a powerful tool for high-throughput discovery. Any attempt at compound screening miniaturization must address the significant scaling inefficiencies associated with library handling and distribution. Eschewing microplate-based compound collections for one-bead-one-compound (OBOC) combinatorial libraries, we have developed hnuSABR (Light-Induced and -Graduated High-Throughput Screening After Bead Release), a microfluidic architecture that integrates a suspension hopper for compound library bead introduction, droplet generation, microfabricated waveguides to deliver UV light to the droplet flow for photochemical compound dosing, incubation, and laser-induced fluorescence for assay readout. Avobenzone-doped PDMS (0.6% w/w) patterning confines UV exposure to the desired illumination region, generating intradroplet compound concentrations (>10 MUM) that are reproducible between devices. Beads displaying photochemically cleavable pepstatin A were distributed into droplets and exposed with five different UV intensities to demonstrate dose-response screening in an HIV-1 protease activity assay. This microfluidic architecture introduces a new analytical approach for OBOC library screening, and represents a key component of a next-generation distributed small molecule discovery platform. PMID- 26815065 TI - Editorial. PMID- 26815066 TI - Civilian injuries due to unexploded ordnance in military training areas in southern Israel. AB - BACKGROUND: The problem of unexploded ordnance (UXO) is global and is usually associated with active or former war zones. Civilian injuries due to UXO in military training areas are not common. METHODS: This is a retrospective case series study based on prospectively collected data on patients who sustained injuries from UXO explosions and were admitted to the Soroka University Trauma Center during a five-year period. RESULTS: Twelve patients were included in this series. All patients were Bedouin and the distribution of injuries was concentrated around the head and upper and lower extremities, with sparing of the torso. CONCLUSION: Awareness and implementation of preventive measures are expected to reduce the incidence of this type of injury. PMID- 26815067 TI - Skeletal injuries sustained during the Haiti earthquake of 2010: a radiographic analysis of the casualties admitted to the Israel Defense Forces field hospital. AB - PURPOSE: To report the distribution and types of skeletal injuries demonstrated on the images taken at the field hospital following the Haiti 2010 earthquake. METHODS: Following the January 12, 2010, earthquake, the State of Israel dispatched a field hospital to Haiti, managing 1,111 patients from January 17, 2010, to January 26, 2010. Four hundred and seven patients (37 %) had 684 radiographic images, most of them (87 %) due to presumed skeletal injuries. RESULTS: There were 224 limb fractures (excluding the hands and feet), with 77 % of them in the lower limbs (30 % femur, 17 % tibial shaft, 16 % ankle). Out of 37 axial skeleton fractures, 30 involved the pelvis (21 anterior posterior, three vertical shear, three lateral compression, three combined). Nine traumatic dislocations (five hips, three shoulders, one knee) were reduced. After reviewing all the digital radiographs, on a PACS-compatible radiography screen, few false diagnoses (2 %) were encountered, with none of them affecting the management of these injuries. CONCLUSIONS: To the best of our knowledge, this is the first report of the radiological results emerging from a field hospital following a mass casualty event. Laptop personal computer-based workstations provide an adequate solution for radiographic image viewing in a field hospital setting. Recognition of the prevalence and distribution of skeletal injuries can improve the preparedness of such delegations before departure in the future. PMID- 26815068 TI - Penetrating peripheral vascular injury management in a Sri Lankan military hospital. AB - PURPOSE: Vascular injuries in austere military conflict settings are a challenging problem. The goal of the current study was to analyze the unique features associated with the management and early outcome of penetrating vascular injuries resulting from the conflict in Sri Lanka. METHODS: All adults with extremity vascular injuries admitted to the Military Base Hospital Anuradhapura in an eight-month period were prospectively recorded in a data sheet and retrospectively analyzed. Mechanism, location, method of repair, and outcomes were analyzed. RESULT: Out of a total of 5,821 combat-related casualties, there were 128 victims with vascular injuries (2.2 %). The overall limb salvage rate was 83 % with an all-cause mortality of 3.1 %. Combined arterial and venous injuries were most common (44 %), predominantly in the popliteal zone. Among the arterial injuries, 70 % were repaired with a vein interposition graft and 7 % were primarily repaired. The majority of the venous injuries (54 %) were ligated. Twenty early major complications were recorded. A temporary intraluminal shunting technique was applied in the 14 most severely injured patients. This patient population was followed up for an average of 35 days institutionally before they were referred to rehabilitation (60 %) or transferred to other institutions (26 %). CONCLUSIONS: Vascular reconstruction using vein, combined with a wound management strategy and early fasciotomy, resulted in a high limb salvage rate and remarkably low infection, delayed amputation, and mortality rates. Management of combat vascular injuries based on clinical guidance is feasible and leads to good outcome in a minimally equipped setting during local military conflicts. Surgeons in military hospitals should be trained in vascular injury repair to save the lives and functional limbs of patients. PMID- 26815069 TI - Rhabdomyolysis: risk factors and incidence in polytrauma patients in the absence of major disasters. AB - PURPOSE: Rhabdomyolysis is a syndrome caused by musculoskeletal tissue damage that leads to the release of large amounts of intracellular elements, which particularly affect renal function. The most common causes are severe trauma, ischemia, surgical procedures, and drug abuse. We aimed to determine the incidence of rhabdomyolysis by measuring muscle injury markers (CK, myoglobin), to identify pre/post-admission as well as iatrogenic risk factors for rhabdomyolysis in severe polytrauma, to clarify the relevance of orthopedic injuries and surgical treatment in the onset/worsening of rhabdomyolysis, and to correlate risk factors with its main complication-acute renal failure (ARF). METHODS: Prospective study of severe polytrauma patients (Injury Severity Score (ISS) >15), with CK and myoglobin values measured at admission and after 24, 48, and 72 h. Peak values, variations between admission and peak, and variations between admission and day 3 were all determined. The correlations of those values with the onset of ARF and other negative outcomes were assessed. RESULTS: A total of 57 consecutive patients with a median ISS of 29 were included. ARF was present in 20 patients (38 %). CK-0 level was correlated with male gender (p < 0.027) and ISS (0.014); Mb-0 level was correlated with hypovolemic shock (0.003) and skeletal fracture (p < 0.043). CK-max was correlated with surgery (p < 0.038) and surgery duration (p < 0.014); Mb-max was correlated with surgery (p < 0.002) and anesthesia duration (p < 0.005). Delta-CK was correlated with surgery (p < 0.01) and surgery duration (p < 0.017), and Delta0-3-CK was correlated with surgery (p < 0.042). Logistic regression analysis found relationships between Delta0-3-CK and both ICU admission (p < 0.003) and MODS (p < 0.012), and between Mb-max and ARF (p < 0.034). CONCLUSION: We found that a large number of factors are implicated in CK and Mb variations. Rhabdomyolysis is a very frequent complication, but increase in CK marker alone does not seem to be correlated with the incidence of ARF. Therefore, Mb level should be considered in this group of patients. PMID- 26815071 TI - Ottawa versus Bernese: which is better? AB - PURPOSE: Trauma of the foot and ankle is commonly seen in the emergency service. For most patients, fractures cannot be ruled out without radiography. The aim of this study is to consider these injured patients in the light of the Ottawa ankle rules and the Bernese ankle rules. METHODS: Our study is a randomized, prospective clinical study. This study was performed during a 24-month period in the Suleyman Demirel University Emergency Medicine Service. A total of 962 adult patients with foot and ankle pain or tenderness following trauma incurring within the previous 10 days were included in the study. Patients were examined only by physicians who had been trained in the correct application of the Ottawa ankle rules and the Bernese ankle rules. All patients were X-rayed with standardized anterior-posterior and lateral radiographs of the ankle and foot, regardless of whether the Ottawa ankle rules and the Bernese ankle rules were positive or negative. The sensitivity and specificity of the Ottawa and Bernese ankle rules according to the study results regarding the correlation between physical examination and radiography were calculated. RESULTS: For the Ottawa ankle rules, the sensitivity was 74.8 %, specificity was 68.6 %, false-negative ratio was 15.1 %, and the false-positive ratio was 46.3 %. For the Bernese ankle rules, the sensitivity was 55.7 %, specificity was 79 %, false-negative was ratio 21.4 %, and the false-positive ratio was 43.7 %. CONCLUSION: These data suggest that the Ottawa ankle rules are more sensitive than the Bernese ankle rules to accurately identify the fracture, but they are still not 100 % reliable. PMID- 26815070 TI - Nailing versus plating for comminuted fractures of the distal femur: a comparative biomechanical in vitro study of three implants. AB - PURPOSE: The purpose of our study was to determine the biomechanical properties of three different implants utilized for internal fixation of a supracondylar femur fracture. The retrograde supracondylar nail (SCN), the less invasive stabilization system plate (LISS) and the distal femoral nail (DFN) were tested and their biomechanical properties compared. METHODS: Twenty pairs of fresh frozen human femura were used. Each femur was osteotomised to simulate a comminuted supracondylar fracture (AO/OTA 33.A3) and then randomized to fracture fixation with either SCN (n=9) or LISS (n=9). Each contralateral femur was stabilized with DFN as a control (n=18). Two femur pairs were spent on pretesting. All femura were subjected to axial (10-500 N) and torsional (0.1-14 Nm) loading. RESULTS: Eighteen matched femur pairs were analyzed. The post loading median residual values were 49.78, 41.25 and 33.51% of the axial stiffness of the intact femur and 59.04, 62.37 and 46.72% of the torsional stiffness of the intact femur in the SCN, LISS and DFN groups. There were no significant differences between the three implants concerning axial and torsional stiffness. CONCLUSIONS: All implants had sufficient biomechanical stability under physiological torsional and axial loading. All three implants have different mechanisms for distal locking. The SCN nail with the four-screw distal interlocking had the best combined axial and torsional stiffness whereas the LISS plate had the highest torsional stiffness. PMID- 26815072 TI - Impact of ulnar styloid fractures in nonoperatively treated distal radius fractures. AB - PURPOSE: The effect of an ulnar styloid fracture (USF) on the stability of nonoperatively treated distal radius fractures (DRF) is unknown. The aim of this study was to evaluate the influence of USFs on the dislocation of DRFs treated by closed reduction. METHODS: Standardized radiographs of 100 nonoperatively treated DRFs were evaluated. DRFs with a USF were compared to DRFs without a USF with respect to dorsal tilt, radial inclination, and ulnar variance. RESULTS: We evaluated the radiographs of 100 DRFs in 99 consecutive patients, of whom 84 were women. An accompanying USF was present in 58 wrists, of which 49 were displaced. On the trauma radiograph, the USF group showed significantly more overall dislocation. After closed reduction, fracture position improved, and no significant differences in dislocation were observed between groups. After a mean of 42 days, radial inclination significantly decreased if a USF was present. When USF displacement was taken into account, significantly more ulnar variance occurred in the displaced USF group on the trauma and follow-up radiograph compared to the nondisplaced USF group and no-USF group. CONCLUSIONS: The results of this study show that presence of a dislocated USF in patients with a DRF is associated with a worse position directly after trauma, and with recurrence of radial shortening after adequate reduction. These results warrant early radiologic follow-up in patients with reduced combined DRFs and USFs in order to evaluate the redislocation of the distal radius. Early detection of redislocation in these combined fractures may induce early surgical intervention. PMID- 26815073 TI - Locking Compression Plates are more difficult to remove than conventional non locking plates. AB - PURPOSE: Locking Compression Plates (LCPs) have been introduced in the last decade. Clinicians have the impression that hardware removal of LCPs are more difficult and associated with more complications than conventional (non-locking) plates. Therefore, this study compares the complication rates of Locking Compression Plate (LCP) removal and conventional non-locking plate removal. PATIENTS AND METHODS: Patients who underwent open reduction and internal fixation and subsequent hardware removal at the Department of Trauma Surgery at our Level 1 Trauma Centre between 1993 and 2007 were included through the hospital's information system. The primary outcome measure was the occurrence of complications during implant removal. RESULTS: A total of 210 patients were included. The females were significantly older than the males [median age, 51.5 vs. 42.6 years (p < 0.001)]. The median operation time of LCP removal was significantly longer than the operation time of non-locking plate removal (72 vs. 54 min, p < 0.001). In the total study population, complications during implant removal occurred in 25 patients (11.9%). The complication rate of conventional non-locking plate removal was 2.5%. The complication rate of LCP removal was significantly higher (17.7%, p = 0.001). CONCLUSION: LCP removal is associated with significantly more complications than conventional non-locking plate removal. The indication for removal of locking compression should be made cautiously, and surgical instruments for LCP removal should be optimized. PMID- 26815074 TI - No additional value of routine check X-rays after internal fixation of hip fractures. AB - PURPOSE: Annually approximately 18,044 patients are admitted to Dutch hospitals with hip fractures. This is an increasing demand for medical care due to the increasing amount of elderly people. Although previous studies showed that routine check of X-rays following hip fracture surgery is unnecessary, it remains routine in most clinics in the Netherlands. In addition to the radiation exposure to the patient, it is painful and leads to unnecessary costs. This study aims to establish if routine check X-rays 1 day after internal fixation for hip fracture with adequate image intensifier guidance influence postoperative management. PATIENTS AND METHODS: A retrospective study was performed for all patients undergoing internal fixation of hip fractures with image intensifier guidance in the period from January 2006 until December 2007 in our hospital. RESULTS: In that period 294 patients underwent internal fixation of hip fractures, 254 underwent a check X-ray and were included in this study. In only two patients the check X-ray did change patient management. CONCLUSION: A check X-ray following internal fixation of hip fractures after adequate peroperative image intensifier guidance is not useful. Dismissing this unuseful medical investigation, leads to less radiation exposure, less pain and less costs. PMID- 26815075 TI - Management of blunt tracheobronchial trauma in the pediatric age group. AB - INTRODUCTION: Tracheobronchial rupture (TBR) due to blunt chest trauma is a rare but life-threatening injury in the pediatric age group. The aim of this study was to propose a treatment strategy including bronchoscopy, surgery and extracorporeal membrane oxygenation (ECMO) to optimize the emergency management of these patients. METHODS: We reviewed a series of 27 patients with post traumatic TBR treated since 1996 in our pediatric trauma center. RESULTS: Seven cases had persistent and large volume air leaks. Flexible bronchoscopy was performed in cases of persistent or large volume air leaks. It permitted accurate visualization of the rupture and its extent. It allowed for a clear-cut positioning of the endotracheal tube. Five were managed operatively. Four cases were considered to be life-threatening because of the combination of severe respiratory distress with hemodynamic instability. One of them had severe tracheal laceration and died. Another one had bilateral bronchi disconnection. Based on clinical and endoscopic findings, surgical repair was performed using extracorporeal membrane oxygenation as a ventilatory support. It provided quick relief from the injury, which was previously expected to result in a fatal issue. CONCLUSIONS: Prompt diagnosis and accurate management of surviving patients admitted to emergency rooms are necessary. Bronchoscopy remains a critical diagnosis step. Surgery is warranted for large tracheobronchial tears and ECMO could be beneficial as supportive therapy for selected cases. PMID- 26815076 TI - The comparison of the effects of hot milk and hot water scald burns and factors effective for morbidity and mortality in preschool children. AB - PURPOSE: Scald burns are the leading cause of burns in children, especially in those younger than 5 years of age, however, they are easily preventable. Our aim in this study was to emphasise the importance and impact of scald burns caused by hot milk. METHODS: A total of 334 patients below seven years of age were included in this study. Of these, 252 were admitted with acquired hot water scald burns (Group 1) and 82 with hot milk scald burns (Group 2) between August 2009 and September 2010. Demographic data of the patients were retrospectively investigated. RESULTS: The depth of the burns was determined to be higher in Group 2 (p < 0.001). The total burnt body surface area in Group 1 and Group 2 were 17.1 +/- 12.3 and 16.3 +/- 10.9 (p = 0.99), respectively. Skin grafting was performed in 23 patients in Group 1 and 16 patients in Group 2 (p = 0.01) and complications developed in three patients in Group 1 and in five patients in Group 2 (p = 0.01). The mean length of hospital stay was 9.1 +/- 7.4 days in Group 1 and 14.9 +/- 9.8 days in Group 2 (p < 0.001) and the mortality rates were similar between the two groups. CONCLUSIONS: More emphasis should be placed on the effects of hot milk scalding due to its ominous clinical course and the high healthcare costs associated with this type of scalding. We believe that taking simple precautions would help reduce the physical, psychological effects and financial consequences of hot milk scalds. PMID- 26815077 TI - Prophylactic sequential bronchoscopy after inhalation injury: results from a three-year prospective randomized trial. AB - OBJECTIVE: That the prophylactic, sequential use of bronchoscopy after inhalation injury as a therapeutic tool to remove secretions and carbonaceous material and to screen for the early detection of pneumonia will improve outcome. METHODS: A three-year prospective randomized trial at a regional burn center. RESULTS: Thirty-three patients with inhalation injury requiring mechanical ventilation were admitted over three years. The bronchoscopy group had a higher initial carboxyhemoglobin level at 11.9 % (95 % CI +/- 9.6 %) versus the control group at 9.9 % (95 % CI +/- 5.7 %, p = 0.7). There was no difference in the incidence of pneumonia between groups (p = 0.6). There was a trend toward fewer days of antibiotic use in the bronchoscopy group, at 4.5 days (95 % CI +/- 4.5 days) versus 9.3 days (95 % CI +/- 7.1 days, p = 0.3). Fewer patients were treated with antibiotics in the bronchoscopy group (4/13, 31 %) versus the control group (9/15, 60 %, p = 0.1). There was a statistically significant difference in the morbidity that favored the bronchoscopy group (3/13, 23 %) over the control group (9/15, 60 %, p = 0.04). There was no statistically significant difference between the two groups in days of mechanical ventilation (bronchoscopy 5.1 days, 95 % CI +/- 3.6 days, control 6.7 days, 95 % CI +/- 6.3 days, p = 0.7), ICU days (bronchoscopy 10 days, 95 % CI +/- 10 days, control 18 days, 95 % CI +/- 12 days, p = 0.4), and hospital days (bronchoscopy 21 days, 95 % CI +/- 12 days, control 26 days, 95 % CI +/- 12 days, p = 0.5), although the trends favored the bronchoscopy group for all of the endpoints. CONCLUSIONS: In conclusion, this program of scheduled, sequential bronchoscopy after inhalation injury showed several strong trends towards less morbidity, fewer days of mechanical ventilation, and a shorter length of stay. There was also a strong trend towards less antibiotic use and a shorter duration of treatment. This data is promising and should promote a larger, multi-institutional trial in the future. PMID- 26815078 TI - The impact of early diagnostic laparoscopy on the prognosis of patients with suspected acute mesenteric ischemia. AB - PURPOSE: To assess the impact of early diagnostic laparoscopy in patients with suspected acute mesenteric ischemia in whom other diagnostic studies are inconclusive or unavailable. METHODS: The medical records of patients who underwent diagnostic laparoscopy with a preoperative diagnosis of acute mesenteric ischemia between January 2008 and January 2012 were reviewed. The patients who had a preoperative diagnosis of acute mesenteric ischemia based on computed tomography or angiography were excluded. Outcome variables were the time between admission and diagnostic laparoscopy, overall revascularization rate, successful revascularization rate, and in-hospital mortality rate. RESULTS: Fifty three patients were included in the study. Twelve patients (22.6 %) had negative diagnostic laparoscopy. In 43 patients (77.4 %) who were found to have acute mesenteric ischemia at diagnostic laparoscopy, the mean time between admission and diagnostic laparoscopy, overall revascularization rate, successful revascularization rate, and in-hospital mortality rate were 10.2 h, 32.5 %, 13.9 %, and 74.4 %, respectively. The mean time between admission and diagnostic laparoscopy was significantly shorter in patients who underwent successful revascularization, and in those who survived with or without developing short bowel syndrome. CONCLUSIONS: Diagnostic laparoscopy is a safe and reliable diagnostic tool that can have a positive impact on the prognosis of patients with suspected acute mesenteric ischemia if carried out in a timely manner when radiological diagnostic studies are inconclusive or unavailable. PMID- 26815080 TI - ESTES News. PMID- 26815079 TI - Risk factors and management of anticoagulant-induced intramural hematoma of the gastrointestinal tract. AB - INTRODUCTION: Intramural intestinal hematoma is considered a rare complication of overanticoagulation in elderly patients. Nevertheless, this clinical entity is increasingly being reported in the literature, and its incidence is predicted to increase further as a result of the wide use of long-term anticoagulation in an aging population. However, data regarding the risk factors and optimal management of this unusual complication in patients on phenprocoumon/warfarin are scarce. PATIENTS AND METHODS: We retrospectively analyzed the medical reports of patients with intramural gastrointestinal hematoma on anticoagulant therapy who were treated in our unit between January 2008 and July 2011. RESULTS: Four consecutive patients were identified during the study period. The mean age of the patients was 80 years. All patients were on uninterrupted anticoagulation with phenprocoumon due to chronic atrial fibrillation. Hematoma was localized in the duodenum in one patient, in the jejunum in two patients, and in the rectum in one patient. Hematoma occurred spontaneously in three patients and following a trauma in one patient. Excessive anticoagulation with an INR of >6 was associated with the development of this complication in all spontaneous cases. A combination of computed tomography and sonography established the diagnosis in all four. Conservative therapy proved successful in two patients, and surgery was necessary in two cases. CONCLUSION: Intramural hematoma of the gastrointestinal tract should be suspected in any patient with abdominal pain or intestinal obstruction under anticoagulant therapy. Emergency physicians and surgeons should be aware of this rare complication, as most such cases will resolve spontaneously under conservative measures without the need for surgery. PMID- 26815081 TI - Towards dial-a-molecule by integrating continuous flow, analytics and self optimisation. AB - The employment of continuous-flow platforms for synthetic chemistry is becoming increasingly popular in research and industrial environments. Integrating analytics in-line enables obtaining a large amount of information in real-time about the reaction progress, catalytic activity and stability, etc. Furthermore, it is possible to influence the reaction progress and selectivity via manual or automated feedback optimisation, thus constituting a dial-a-molecule approach employing digital synthesis. This contribution gives an overview of the most significant contributions in the field to date. PMID- 26815082 TI - DDQ-Mediated Oxidative Radical Cycloisomerization of 1,5-Diynols: Regioselective Synthesis of Benzo[b]fluorenones under Metal-Free Conditions. AB - A regio- and chemoselective oxidative cycloisomerization reaction of acyclic 1,5 diynols has been developed. The reaction proceeds under metal-free reaction conditions with high efficiency and broad functional group tolerance, which offers a general and straightforward access to benzo[b]fluorenones under metal free conditions. The preliminary mechanistic studies revealed the possible involvement of a Meyer-Schuster rearrangement combined with an oxidative radical cyclization. PMID- 26815083 TI - Focus on Compartment Syndrome. PMID- 26815084 TI - Epidemiology, Etiology, Pathophysiology and Diagnosis of the Acute Compartment Syndrome of the Extremity. AB - Due to an insult that causes a pressure elevation in the compartment, which is the limited space surrounded by the unyielding bone and fascia, the circulation is compromised resulting in muscular and neural ischemia and eventually tissue necrosis. The diagnosis of the compartment syndrome has always been based on the clinical symptoms, however, multiple studies suggested that clinical examination alone is insufficient and may result in delayed diagnosis, delayed treatment and serious sequelae. To avoid delayed diagnosis and treatment the use of compartment pressure monitoring has been advised. There is, however, no consensus about the indications for the compartment pressure monitoring, or about the threshold pressure that should be used for dermatofasciotomy. A diagnostic guideline is proposed. PMID- 26815085 TI - Acute Compartment Syndrome of the Upper Extremity. AB - Compartment syndrome of the upper extremity is rare, but happens frequently. It most often affects the forearm, compartment syndromes of the upper arm and hand are seen much more seldom. Early diagnosis and efficient fasciotomy is of highest importance to achieve good outcome and prevent development of Volkmann's ischemic contracture. PMID- 26815086 TI - Compartment Syndrome of the Lower Extremity. AB - Acute compartment syndrome of the lower extremity is a limb-threatening emergency that requires prompt surgical treatment. Early detection and decompression are necessary in order to avoid irreversible damage. In the lower extremity, compartment syndrome may occur around the pelvis, in the thigh, the lower leg or the foot. Acute compartment syndrome of the lower leg is most common. Sometimes, combined compartment syndromes of neighbouring skeletal regions are observed. In this review, the specific clinical symptoms as well as the anatomic and therapeutic characteristics of the acute compartment syndrome of the lower extremity are described. PMID- 26815087 TI - Ischemia-Reperfusion Injury : Pathophysiology and Clinical Implications. AB - The term ischemia-reperfusion injury describes the experimentally and clinically prevalent finding that tissue ischemia with inadequate oxygen supply followed by successful reperfusion initiates a wide and complex array of inflammatory responses that may both aggravate local injury as well as induce impairment of remote organ function. Conditions under which ischemia-reperfusion injury is encountered include the different forms of acute vascular occlusions (stroke, myocardial infarction, limb ischemia) with the respective reperfusion strategies (thrombolytic therapy, angioplasty, operative revascularization) but also routine surgical procedures (organ transplantation, free-tissue-transfer, cardiopulmonary bypass, vascular surgery) and major trauma/shock. Since the first recognition of ischemia-reperfusion injury during the 1970s, significant knowledge has accumulated and the purpose of this review is to present an overview over the current literature on the molecular and cellular basis of ischemia-reperfusion injury, to outline the clinical manifestations and to compile contemporary treatment and prevention strategies. Although the concept of reperfusion injury is still a matter of debate, it is corroborated by recent and ongoing clinical trials that demonstrated ischemic preconditioning, inhibition of sodium-hydrogen exchange and administration of adenosine to be effective in attenuating ischemia reperfusion injury. PMID- 26815088 TI - Plating of Femoral Shaft Fractures: the Experience in an African Teaching Hospital. AB - BACKGROUND: Femoral shaft fractures are common presentation in our trauma units. It is obvious that all these fractures cannot be treated conservatively due to the pressure on trauma beds and thus a suitable method of internal fixation that is feasible in the environment has had to be adopted. OBJECTIVE: This study is a report of our experience with plate fixation of femoral shaft fracture in our environment. DESIGN: A retrospective hospital based study. PATIENT AND METHOD: All patients with femoral shaft fractures stabilized with plates and screws between 1997 and 2004 at the University College Hospital were reviewed. The case notes were retrieved and data extracted from them; all case notes entry gave sufficient information. RESULTS: The fracture pattern showed 56 cases (35.4%) of Type 32-A, 45 cases (28.5%) of Type 32-B and 57 cases (36.1%) of Type 32-C using AO classification. The outcome of treatment was excellent to good in 125 fractures (77.2%). The average time of healing was 20 weeks (range 16-48). Fracture related complications occurred in nine fractures (5.7%) which included deep infection in four fractures (2.5%) and implant failure in five fractures (3.2%). CONCLUSION: Femoral shaft plating gives good result if the principles of fixation is carefully followed and in developing countries where initial cost of procurement of equipments for closed nailing may not be forth coming, it thus provide a safe efficient and low cost method of fixation of femoral shaft fracture. PMID- 26815089 TI - Treating Displaced Distal Forearm Fractures in Children. AB - PURPOSE: Distal forearm fractures are among the most common fractures in children. In the past few years the option of percutaneous pinning has gained more attention in the treatment of unstable fractures. However, it remains unclear in which cases a fracture or its reduction should be considered unstable. STUDY DESIGN: In order to evaluate which type of fractures profit most from additional pinning after closed reduction, we performed a retrospective analysis of 225 consecutive cases using the recently published AO pediatric classification of long bone fractures. RESULTS: After closed reduction, position in the cast was lost in 23% of the cases. The proportion of unstable reductions was much higher in completely displaced fractures. The amount of dislocation was more important than the type of fracture according to the AO classification proposal. CONCLUSIONS: Fully displaced fractures should always be reduced in a setting with pins immediately available. If anatomical reduction cannot be achieved, pinning is advocated. The AO proposal for pediatric long bone fracture classification could be a useful tool to render the diverse studies more comparable. However, the important feature of complete versus subtotal displacement is lacking. PMID- 26815090 TI - Osteitis and Septic Arthritis after Tibial Head Fracture: Results of a Radical Treatment Regime. AB - OBJECTIVES: We report a series of 37 consecutive patients with both bone infection and septic arthritis of the knee following fracture of the proximal tibia. Aim of this study is to evaluate treatment results using a standardized treatment regime. The treatment regime consisted of an aggressive surgical approach to both the bone and the joint. In 61% the joint function was preserved, in the reminder an arthrodesis was required, there were no amputations. The difficulties in dealing with this condition are described as well as the clinical, radiological and occupational results. DESIGN/SETTING: Data collection was prospective. Data gathered at follow up included clinical examination, radiographs and the Rassmussen scoring system. Setting is a bone and joint infection and reconstruction unit of a tertiary referral hospital. PATIENTS/METHODS: Nine patients were female (24.3%). Mean age was 47.7 years (16.6-76.7 years). We classified fracture types according to Schatzker; ofwhich type VI fractures were the largest group with 13 cases. RESULTS: About 3.2 operations where required on average (1-7) for the treatment of infection. For 22 patients the joint function was salvaged. In the remaining cases an arthrodesis was required. CONCLUSIONS: The reported treatment regime gives reliable results for the treatment of combined bone and joint infection of the knee after fracture. In a large group of cases it was possible to salvage joint function. Comparison to other forms of treatment is not possible as there are no reported results so far. PMID- 26815091 TI - The Dynamic Martin Screw: an Alternative for Intracapsular Femoral Neck Fractures? AB - OBJECTIVES: The aim of this study was to determine whether the fixation device known as the dynamic Martin screw (DMS) offers a reasonable alternative for stabilizing intracapsular femoral neck fractures. MATERIALS AND METHODS: A total of 63 patients with intracapsular femoral neck fractures, stabilized between 1993 and 1997 with the DMS, were followed up in this retrospective study in both 1999 and 2002. The patients were on average 64 years of age, with 30 younger and 33 older than 65. The main outcome measurements consisted of union, non-union, aseptic osteonecrosis of the femoral head and implant failure. RESULTS: We determined an overall osteonecrosis rate of 19% (12 of 63) for our patient group after an observation period on average of 83 months. The osteonecrosis rate for undisplaced fractures was 13.2% (5 of 38), and 28% (7 of 25) for displaced fractures. Non-union occurred in 4.8% (3 of 63) and union in 95.2% (60 of 63) of the patient cases. An implant-associated complication involving deep infection occurred in one case, but no example of implant breakage was recorded. CONCLUSIONS: As a method for stabilizing intracapsular femoral neck fractures, the DMS provides treatment results comparable to other sliding hip screws or cannulated screw. PMID- 26815093 TI - Late Reconstruction of a Traumatic Trapeziometacarpal Dislocation with a Semi constrained Prosthesis: A Case Report. AB - Traumatic dislocation of the trapeziometacarpal joint is rare. A stable reduction should be accomplished as soon as possible, usually with K-wiring. In this case of persistent instability a semi-constrained prosthesis was applied successfully. PMID- 26815092 TI - The Approach to Suicide Bombing Attacks: Changing Concepts. AB - Suicide bombing attacks have emerged as a lethal weapon in the hands of terrorist groups. Our aim was to review the medical experience acquired in Israel, Spain, the United Kingdom and the United States in managing terrorist attacks, and prepare medical systems for the difficult task of managing these events. EMS protocols are amended to deal with a large number of victims in an urban setting who must be rapidly evacuated to a medical center where resuscitative as well as definitive care is delivered. A combination of extensive soft tissue damage caused by penetrating injuries, blast injury to the lungs and tympanic membranes, and burns are common among survivors. Preparation must include establishment of a clear chain-of-command lead by a general surgeon who manages the event and is responsible for decisions regarding OR preferences and ICU admissions. The emergency department is re-organized to handle the influx of numerous severely injured casualties. Professional personnel and resources are recruited and re directed away from routine tasks towards treating the victims. This is achieved by deferring non-urgent operations, procedures and imaging studies. Victims are frequently re-assessed and re-evaluated to control chaos, minimize missed injuries and ensure delivery of an adequate level of care. PMID- 26815094 TI - Huge Extrapleural Hematoma After a Blunt Chest Trauma: An Unusual Presentation. AB - Massive extrapleural hematoma secondary to blunt chest trauma is exceedingly rare especially in nonanticoagulated patients. Significant amounts of blood can be sequestered between parietal pleura and the endothoracic facia leading to ventillatory and circulatory disturbances and even death. We report a case of a huge extrapleural hematoma in a non-anticoagulated 70-year-old patient secondary to blunt chest trauma. Etiology, surgical and treatment implications of this injury are briefly discussed. PMID- 26815095 TI - Tubular Remodeling of Massive Cancellous Bone Graft in the Treatment of Long Bone Defects. AB - BACKGROUND: This case report describes the clinical and radiological result at the 4.5-year follow-up after an extensive reconstruction of the femoral diaphysis using autologous cancellous bone graft. The radiological study including axial tomography demonstrates secondary remodelling to form tubular diaphyseal bone. METHODS: A patient with an existing hip fusion, who sustained a fracture of the proximal femur 12 years later, was treated by open internal fixation using a plate and screws. Infection followed which became chronic, causing bone resorption and necrosis and producing a septic non-union. Reconstruction in two stages was performed: open radical debridement which ended with a 14.5 cm diaphyseal defect of the femur, temporary alloplastic spacer interposition and secondary de-arthrodesis of the hip with massive autologous cancellous grafts into the induced foreign body membrane left by the spacer. Fixation was provided by a plate and screws. RESULTS: The femur was free of infectious recurrence at 4.5 years. The patient walks without crutches with a shortened lower limb using a leg length compensation shoe and a painfree sine-sine hip arthroplasty. The former bone defect is fully remodelled into new cortical bone. X-ray and CT-scan demonstrate the tubular form of the reconstructed bone. CONCLUSION: This clinical case demonstrates the restoration of a medullar cavity after massive cancellous bone grafting of a diaphyseal defect of the femur. The question remains open as to whether the foreign body membrane has only a simple passive protective function against extraosseous bone resorbing factors or whether it functions actively by producing growth factors or other beneficial bone inducing factors. PMID- 26815097 TI - Planning Analysis of Knee-Adjacent Deformities : I. Frontal Plane Deformities. AB - The planning analysis of leg deformities around the knee joint is based on a standardized clinical examination and on long leg standing anteroposterior (AP) radiographs, which may be complemented by spot-film radiographs and stress radiographs.The principles of true-nominal analysis in six steps are used to characterize the deformity and plan the corrective osteotomy:1. Drawing in the anatomic points of reference.2. Establishing the mechanical weight-bearing axis.3. Determining the axis and orientation angles around the knee joint.4. Determining the correction goal.5. Deciding on the osteosynthesis technique and the osteotomy level.6. Measuring the angle of correction.All the steps are exemplified on a valgus deformity and a varus deformity. PMID- 26815096 TI - Secondary Collapse of an Expandable Cage After Vertebral Corpectomy. AB - Expandable vertebral body replacement systems have been increasingly used for anterior stabilization of spine. We report a secondary collapse of an expandable vertebral body replacement system. This specific complication has not been reported in the literature so far. The most obvious reason for failure was insufficient tightening of a locking screw. This paper emphasizes the importance of correct technical application. PMID- 26815101 TI - Current management of enterocutaneous fistulas. PMID- 26815100 TI - Social defeat leads to changes in the endocannabinoid system: An overexpression of calreticulin and motor impairment in mice. AB - Prolonged and sustained stimulation of the hypothalamo-pituitary-adrenal axis have adverse effects on numerous brain regions, including the cerebellum. Motor coordination and motor learning are essential for animal and require the regulation of cerebellar neurons. The G-protein-coupled cannabinoid CB1 receptor coordinates synaptic transmission throughout the CNS and is of highest abundance in the cerebellum. Accordingly, the aim of this study was to investigate the long lasting effects of chronic psychosocial stress on motor coordination and motor learning, CB1 receptor expression, endogenous cannabinoid ligands and gene expression in the cerebellum. After chronic psychosocial stress, motor coordination and motor learning were impaired as indicated the righting reflex and the rota-rod. The amount of the endocannabinoid 2-AG increased while CB1 mRNA and protein expression were downregulated after chronic stress. Transcriptome analysis revealed 319 genes differentially expressed by chronic psychosocial stress in the cerebellum; mainly involved in synaptic transmission, transmission of nerve impulse, and cell-cell signaling. Calreticulin was validated as a stress candidate gene. The present study provides evidence that chronic stress activates calreticulin and might be one of the pathological mechanisms underlying the motor coordination and motor learning dysfunctions seen in social defeat mice. PMID- 26815098 TI - Chronic Inflammatory Diseases and Endothelial Dysfunction. AB - Chronic inflammatory diseases are associated with increases in cardiovascular diseases (CVD) and subclinical atherosclerosis as well as early-stage endothelial dysfunction screening using the FMD method (Flow Mediated Dilation). This phenomenon, referred to as accelerated pathological remodeling of arterial wall, could be attributed to traditional risk factors associated with atherosclerosis. Several new non-invasive techniques have been used to study arterial wall's structural and functional alterations. These techniques (based of Radio Frequency, RF) allow for an assessment of artery age through calculations of intima-media thickness (RF- QIMT), pulse wave rate (RF- QAS) and endothelial dysfunction degree (FMD). The inflammatory and autoimmune diseases should now be considered as new cardiovascular risk factors, result of the major consequences of oxidative stress and RAS (Renin Angiotensin System) imbalance associated with the deleterious effect of known risk factors that lead to the alteration of the arterial wall. Inflammation plays a key role in all stages of the formation of vascular lesions maintained and exacerbated by the risk factors. The consequence of chronic inflammation is endothelial dysfunction that sets in and we can define it as an integrated marker of the damage to arterial walls by classic risk factors. The atherosclerosis, which develops among these patients, is the main cause for cardiovascular morbi-mortality and uncontrolled chronic biological inflammation, which quickly favors endothelial dysfunction. These inflammatory and autoimmune diseases should now be considered as new cardiovascular risk factors. PMID- 26815102 TI - The surgical anatomy and etiology of gastrointestinal fistulas. AB - BACKGROUND: Fistulas are abnormal communications between two epithelial surfaces, either between two portions of the intestine, between the intestine and some other hollow viscus, or between the intestine and the skin of the abdominal wall. The etiology of intestinal fistulas is in most cases a result of multiple contributing factors. Despite significant advances in their management over the past decades, intestinal fistulas remain a major clinical problem, with a high overall mortality rate of up to 30% due to the high rate of complications. This paper aims to describe classification systems based on the anatomy, physiology and etiology that may be helpful in the clinical management of intestinal fistulas. METHODS: On the basis of anatomical differences, fistulas can be classified based by the site of origin, by site of their openings, or as simple or complex. Physiologic classification as low, moderate or high output fistulas is most useful for the non-surgical approach. Concerning the etiology, we classified the possible causes as (postoperative) trauma, inflammation, infection, malignancy, radiation injury or congenital. CONCLUSION: Fistula formation can cause a number of serious or debilitating complications ranging from disturbance of fluid and electrolyte balance to sepsis and even death. They still remain an important complication following gastrointestinal surgery. PMID- 26815103 TI - Metabolic consequences of patients with gastrointestinal fistulas. AB - METHODS AND MATERIALS: The historical highlights of the management of fistulas of the gastrointestinal tract during the past century are presented briefly, together with the significant lessons learned from the studies published in the literature. DISCUSSION: The evolution from predominantly operative or technical approaches to comprehensive multidisciplinary management of metabolic and nutritional support, which are essential to optimal fistula closure, and morbidity and mortality outcomes are discussed. The importance of achieving hemodynamic stability, fluid and electrolyte homeostasis, fistula effluent control, protection of the skin, control of infection and sepsis, and cardiopulmonary and major organ support, preferably by specially trained and motivated teams in critical care units of institutions with the interest, resources, and skills in managing the metabolic consequences of gastrointestinal fistula patients, is emphasized. The current status of the nutritional and metabolic support of patients with gastrointestinal tract fistulas is outlined and discussed briefly. CONCLUSIONS: The optimal metabolic and nutritional management of patients with gastrointestinal tract fistulas is an extraordinary and daunting challenge which has yet to be perfected, demonstrated, and applied universally. Much education, research, motivation, proficiency, and concerted conscientious effort will be required in order to achieve this elusive but noble goal. Some suggestions for achieving success in this endeavor are proffered, consistent with the senior author's philosophy, which has evolved during a half century of experience and endeavor in this vital area. PMID- 26815104 TI - Nutritional support in patients with gastrointestinal fistula. AB - Gastrointestinal fistulas (GIFs) arise as a complication of the surgical treatment of a number of malignant and non-malignant diseases. Fluid loss and electrolyte and nutritional imbalance are related to increased morbidity and mortality in these patients. A multidisciplinary approach under the leadership of the surgeon is essential for successful therapy. Because complication rates are higher in malnourished patients with fistulas, enteral or total parenteral nutritional (TPN) support should be initiated after the patient has been stabilized with respect to fluid loss, acid-base, and sepsis. Pharmacotherapy with somatostatin and octreotide has been shown to reduce fistula output and shorten closure time. PMID- 26815105 TI - Anatomy-based surgical strategy of gastrointestinal fistula treatment. AB - Anatomic delineation of a gastrointestinal fistula is essential in assessing the likelihood of spontaneous closure or to plan the surgical management. Computed tomography (CT) enterography and/or fistulograms provide invaluable information. The surgical strategy should carefully consider the when and how, as well as the special clinical situations that may arise following radiotherapy, the inaccessible or "frozen abdomen", and enteroatmospheric fistulas (EAFs). New operations like those performed in bariatric surgery, and the wide acceptance of the damage-control philosophy in severe trauma, have given rise to new types of fistulas and increased the occurrence of others. When confronted with this difficult complication, the surgeon must always exercise patience and restraint, and be open-minded about the different surgical alternatives to solve the problem. PMID- 26815106 TI - Abdominal wall reconstruction in patients with enterocutaneous fistulas. AB - Enterocutaneous fistulas (ECFs) remain a feared complication of surgery, particularly in acute care and trauma patients. Despite advances in medical and surgical therapies, ECFs are associated with significant morbidity and mortality; in addition, significant health care resources are consumed in their treatment. Because of the frequency nowadays of open-abdomen and damage-control surgery, of aggressive treatment for abdominal compartment syndrome, and of necrotizing soft tissue infections of the abdominal wall, ECFs are becoming common; so are enteroatmospheric fistulas (EAFs), which represent a new entity where the lumen of the intestine is directly exposed to the outside environment and has no track through subcutaneous or cutaneous tissue. The surgical management of abdominal wall defects, including ECFs and/or EAFs, is often associated with major hernias and other complexities. Careful planning and advanced surgical techniques are required, often involving the use, alone or in combination, of biologic mesh and composite tissue transfer. The treatment of ECFs in patients with large abdominal wall defects is challenging, but with proper techniques, the results can be excellent. Biologic mesh is the mesh of choice in such patients. PMID- 26815107 TI - Enterocutaneous fistulas: an overview. AB - Enterocutaneous fistulas remain a difficult management problem. The basis of management centers on the prevention and treatment of sepsis, control of fistula effluent, and fluid and nutritional support. Early surgery should be limited to abscess drainage and proximal defunctioning stoma formation. Definitive procedures for a persistent fistula are indicated in the late postoperative period, with resection of the fistula segment and reanastomosis of healthy bowel. Even more complex are the enteroatmospheric fistulas in the open abdomen. These enteric fistulas require the highest level of multidisciplinary approach for optimal outcomes. PMID- 26815109 TI - Characteristics of polytrauma patients with posttraumatic stress disorder in a level 1 trauma center. AB - AIMS: The aims of this study were to determine if the severity of injury is related to the prevalence of posttraumatic stress disorder (PTSD) in polytrauma patients and to review the personality traits of patients with PTSD. METHODS: During 2006 and 2007, 252 polytrauma patients were treated at the Medical Centre Haaglanden in The Hague, The Netherlands. Of the 174 survivors, 53 adult patients were traced and sent questionnaires. They were screened for PTSD and personality traits, coping styles, and negative cognitions, and their level of social support were assessed. RESULTS: PTSD was demonstrated in 22.6% of the patients. CONCLUSIONS: An increased level of neuroticism, negative cognitions regarding themselves, and active dealing were found to be significant predictors of PTSD. However, we found no relation between the injury severity score and the prevalence of PTSD. PMID- 26815108 TI - Uncommon acquired fistulae involving the digestive system: summary of data. AB - PURPOSE: Most gastrointestinal fistulae commonly occur following surgery. A minority is caused by a myriad of other etiologies and is termed by some as "uncommon fistulae". The aim of this study was to review these fistulae and their treatment. METHODS: A literature review was carried out. Searches were conducted in Pubmed and related references reviewed. RESULTS: Except for Crohn's disease and diverticulitis, "uncommon fistulae" are described in case reports or very small case series. Most of the patients were treated by surgery. CONCLUSIONS: The anatomic features of the fistula and the etiology usually dictate the approach. Most patients will eventually need surgery to resolve this pathology. PMID- 26815110 TI - Treatment of the displaced femoral neck fractures: indications and limits of osteosynthesis. AB - PURPOSE: Opinions about the optimal treatment of displaced femoral neck fractures in the elderly are still divided. The two main options are internal fixation and arthroplasty. The aim of our study was to determine the most adequate surgical procedure for displaced, Garden type III-IV femoral neck fractures: which patients should undergo an osteosynthesis or primary arthroplasty, with the least prospect of complications? METHODS: We analyzed 489 femoral neck fractures treated by percutaneous osteosynthesis. We also compared the results of displaced fractures treated with primary arthroplasty versus secondary arthroplasty performed due to the failure of primary osteosynthesis. RESULTS: The rate of redisplacement in the Garden type III group was 7.6%, and in the Garden type IV group, it was 25.5%, mainly in the case of subcapital fractures. Also, walking ability was examined 4 months after injury. In the ASA score II-III group, most of the patients were able to walk with or without walking aids, but in the case of ASA score IV, most of them were immobile or died during the hospital or posthospital phase. Our research also proved that, in cases of femoral neck fractures treated with primary arthroplasty, the complication rate is lower than after secondary arthroplasty due to failure of the primary osteosynthesis. CONCLUSIONS: Based on our results, we recommend osteosynthesis in the case of Garden type III femoral neck fractures and, in turn, arthroplasty with respect to the high rate of early redisplacement in the case of Garden type IV fractures, especially in the case of subcapital fractures. For patients confined to a bed and in poor general condition (ASA score IV), the first choice treatment option is the minimally invasive percutaneous osteosynthesis. PMID- 26815111 TI - Telesurgical evaluation of stable thoracic trauma patients: a feasibility study. AB - BACKGROUND: We evaluated a robotic telesurgical platform in managing thoracic trauma in an animal model. STUDY DESIGN: The da Vinci((r)) robot was used to evaluate and treat a random number of blinded injuries in ten porcine thoraces. RESULTS: Ninety-five percent of injuries were correctly identified. The median survey time was 20.5 min (range 16-63 min). The mean time to repair lung lacerations was 19.8 min (range 14-27.5 min) and to evacuate the hemothoraces, it was 5.3 min (range 4.5-6.5 min). Diaphragmatic lacerations required repositioning of the ports and the robot. Only two out of five lacerations were successfully repaired (mean time 38.8 min, range 32.5-45 min). All aortic injuries were correctly identified. One subject died of a pre-existing pneumonia. CONCLUSIONS: A robotic telesurgical approach to the evaluation of stable thoracic trauma patients is safe and feasible in a porcine model. Diaphragmatic injuries can be repaired but require repositioning of the robot. PMID- 26815112 TI - Clinical evaluation of end caps in elastic stable intramedullary nailing of femoral and tibial shaft fractures in children. AB - BACKGROUND: Elastic stable intramedullary nailing (ESIN) may be complicated by the loss of reduction following push out of the nails at the entry site in unstable femoral and tibial fractures, especially in older and heavier children and following technical failures. An end cap system addressing this complication was evaluated clinically. METHODS: In a retrospective case series, 49 femoral and five tibial fractures in 54 pediatric patients treated by ESIN and end caps were documented in two European tertiary centers. End caps were used to interlock standard ESIN nails. The results were evaluated regarding difficulties in the placement and removal of the end cap system, fracture stability and healing, and return to normal activities by analyzing patient charts and X-rays. RESULTS: Fifty-three of 54 fractures were stabilized sufficiently with ESIN and end caps. Loss of reduction was observed in one patient, requiring additional surgery. Six complications were observed, five of which were not related to end caps. There were no significant leg length differences or varus/valgus deformities. A rotational difference of >10 degrees -20 degrees was found in one patient. Removal of the end caps and nails was rated as simple and uncomplicated in 35/37 cases. CONCLUSIONS: End caps avoided postoperative instability in the majority of pediatric patients with lower limb shaft fractures, even in heavier, older patients and those with instable fracture types. End caps, however, will not compensate for operative technical insufficiency concerning reduction or nail placement. To maximize the stability of ESIN-instrumented unstable fractures, end caps require properly placed nails. PMID- 26815113 TI - Teaching in daily clinical practice: how to teach in a clinical setting. AB - Teaching in the clinical setting is challenging; however, it is the location where students apply their learned facts and learn skills and attitudes most effectively. In order to improve clinical teaching, it is important to know and implement the principles of adult learning. The clinical teacher should know or assess the learners' prior knowledge and skills, as well as their stage of learning, before starting a new teaching session. The learners should be actively involved in the clinical processes. Questions to probe students' deeper understanding and capability to analyze, synthesize, and apply medical knowledge should be an important part of clinical teaching. Regular structured feedback is an important part of any learning experience. PMID- 26815116 TI - Tunable Wide-Angle Tunneling in Graphene-Assisted Frustrated Total Internal Reflection. AB - Electrically tunable permittivity of graphene provides an excellent tool in photonic device design. Many previous works on graphene-based photonic devices relied on variable absorption in graphene, which is naturally small in the optical region, and resonant structures to enhance it. Here we proposed a novel scheme to control evanescent coupling strength by inserting two graphene layers to a frustrated total internal reflection (FTIR) configuration. The resulting structure behaves in a drastically different way from the original FTIR: optical transmission though the structure can be electrically controlled from ~10(-5) to ~1 with little dependency on angle of incidence. This unique feature stems from the fact that the permittivity of doped graphene can be close to zero at a certain photon energy. The electrical controllability of evanescent coupling strength can enable novel design of optical devices. As a proof-of-concept, we designed a waveguide-type optical modulator of a novel operation principle: transmission modulation depends on the electrically controlled existence of a guided-mode of the waveguide, not the variation of the ohmic loss of graphene, resulting in a low insertion loss and a small device footprint. PMID- 26815115 TI - Computational Fluid Dynamic Simulations of Maternal Circulation: Wall Shear Stress in the Human Placenta and Its Biological Implications. AB - INTRODUCTION: In the human placenta the maternal blood circulates in the intervillous space (IVS). The syncytiotrophoblast (STB) is in direct contact with maternal blood. The wall shear stress (WSS) exerted by the maternal blood flow on the STB has not been evaluated. Our objective was to determine the physiological WSS exerted on the surface of the STB during the third trimester of pregnancy. MATERIAL AND METHODS: To gain insight into the shear stress levels that the STB is expected to experience in vivo, we have formulated three different computational models of varying levels of complexity that reflect different physical representations of the IVS. Computations of the flow fields in all models were performed using the CFD module of the finite element code COMSOL Multiphysics 4.4. The mean velocity of maternal blood in the IVS during the third trimester was measured in vivo with dynamic MRI (0.94+/-0.14 mm.s-1). To investigate if the in silico results are consistent with physiological observations, we studied the cytoadhesion of human parasitized (Plasmodium falciparum) erythrocytes to primary human STB cultures, in flow conditions with different WSS values. RESULTS: The WSS applied to the STB is highly heterogeneous in the IVS. The estimated average values are relatively low (0.5+/-0.2 to 2.3+/ 1.1 dyn.cm-2). The increase of WSS from 0.15 to 5 dyn.cm-2 was associated with a significant decrease of infected erythrocyte cytoadhesion. No cytoadhesion of infected erythrocytes was observed above 5 dyn.cm-2 applied for one hour. CONCLUSION: Our study provides for the first time a WSS estimation in the maternal placental circulation. In spite of high maternal blood flow rates, the average WSS applied at the surface of the chorionic villi is low (<5 dyn.cm-2). These results provide the basis for future physiologically-relevant in vitro studies of the biological effects of WSS on the STB. PMID- 26815117 TI - Seed-mediated growth of Au nanorings with size control on Pd ultrathin nanosheets and their tunable surface plasmonic properties. AB - Nanorings made of noble metals such as Au and Ag have attracted particular interest in plasmonic properties since they allow remarkable tunability of plasmon resonance wavelengths associated with their unique structural features. Unfortunately, most of the syntheses for Au nanorings involve complex procedures and/or require highly specialized and expensive facilities. Here, we report a seed-mediated approach for selective deposition of Au nanorings on the periphery of Pd seeds with the structure of an ultrathin nanosheet through the island growth mode. In combination with selective etching of Pd nanosheets, Au nanorings are eventually produced. We can control the outer diameter and wall thickness of the nanorings by simply varying the size of the Pd nanosheets and reaction time. By taking the advantage of this size controllability, the nanorings show tunable surface plasmonic properties in the near infrared (NIR) region arising from both the in-plane dipole and face resonance modes. Owing to their good surface plasmonic properties, the nanorings show substantially enhanced surface-enhanced Raman spectroscopy (SERS) performance for rhodamine 6G, and are therefore confirmed as good SERS substrates to detect trace amounts of molecules. PMID- 26815118 TI - Caveolin-1-dependent activation of the metalloprotease TACE/ADAM17 by TGF-beta in hepatocytes requires activation of Src and the NADPH oxidase NOX1. AB - Transforming growth factor-beta (TGF-beta) plays a dual role in hepatocytes, inducing both pro- and anti-apoptotic responses, the balance between which decides cell fate. Survival signals are mediated by the epidermal growth factor receptor (EGFR) pathway, which is activated by TGF-beta. We have previously shown that caveolin-1 (CAV1) is required for activation of the metalloprotease tumour necrosis factor (TNF)-alpha-converting enzyme/a disintegrin and metalloproteinase 17 (TACE/ADAM17), and hence transactivation of the EGFR pathway. The specific mechanism by which TACE/ADAM17 is activated has not yet been determined. Here we show that TGF-beta induces phosphorylation of sarcoma kinase (Src) in hepatocytes, a process that is impaired in Cav1(-/-) hepatocytes, coincident with a decrease in phosphorylated Src in detergent-resistant membrane fractions. TGF beta-induced activation of TACE/ADAM17 and EGFR phosphorylation were blocked using the Src inhibitor PP2. Cav1(+/+) hepatocytes showed early production of reactive oxygen species (ROS) induced by TGF-beta, which was not seen in Cav1(-/ ) cells. Production of ROS was inhibited by both the NADPH oxidase 1 (NOX1) inhibitor STK301831 and NOX1 knock-down, which also impaired TACE/ADAM17 activation and thus EGFR phosphorylation. Finally, neither STK301831 nor NOX1 silencing impaired Src phosphorylation, but PP2 blocked early ROS production, showing that Src is involved in NOX1 activation. As expected, inhibition of Src or NOX1 increased TGF-beta-induced cell death in Cav1(+/+) cells. In conclusion, CAV1 is required for TGF-beta-mediated activation of TACE/ADAM17 through a mechanism that involves phosphorylation of Src and NOX1-mediated ROS production. PMID- 26815119 TI - [Neuroradiological diagnosis and treatment of spontaneous intracranial hypotension]. PMID- 26815120 TI - Nano-Computed Tomography: Technique and Applications. AB - Nano-computed tomography (nano-CT) is an emerging, high-resolution cross sectional imaging technique and represents a technical advancement of the established micro-CT technology. Based on the application of a transmission target X-ray tube, the focal spot size can be decreased down to diameters less than 400 nanometers (nm). Together with specific detectors and examination protocols, a superior spatial resolution up to 400 nm (10 % MTF) can be achieved, thereby exceeding the resolution capacity of typical micro-CT systems. The technical concept of nano-CT imaging as well as the basics of specimen preparation are demonstrated exemplarily. Characteristics of atherosclerotic plaques (intraplaque hemorrhage and calcifications) in a murine model of atherosclerosis (ApoE (-/-)/LDLR(-/-) double knockout mouse) are demonstrated in the context of superior spatial resolution in comparison to micro-CT. Furthermore, this article presents the application of nano-CT for imaging cerebral microcirculation (murine), lung structures (porcine), and trabecular microstructure (ovine) in contrast to micro-CT imaging. This review shows the potential of nano-CT as a radiological method in biomedical basic research and discusses the application of experimental, high resolution CT techniques in consideration of other high resolution cross-sectional imaging techniques. KEY POINTS: Nano-computed tomography is a high resolution CT-technology for 3D imaging at sub-micrometer resolution. The technical concept bases on a further development of the established ex-vivo-micro-CT technology. By improvement of the spatial resolution, structures at a cellular level become visible (e.g. osteocyte lacunae). PMID- 26815122 TI - [Birth place of Wilhelm Conrad Rontgen - so it can continue!]. PMID- 26815123 TI - [Certification under the auspices of he DRG]. PMID- 26815121 TI - Application of Dual-Source-Computed Tomography in Pediatric Cardiology in Children Within the First Year of Life. AB - PURPOSE: To assess fields of application and value of dual source computed tomography (DSCT) for diagnostics and therapy in patients with congenital heart disease during their first year of life. Evaluation of image quality, surgical use and radiation exposure of 2nd and 3 rd generation DSCT. MATERIALS AND METHODS: DSCT was applied in 118 cases between January 2012 and October 2014 for diagnostics of congenital heart defects. 2nd generation was used in 91 cases until April 2014 and 3 rd generation in 27 cases during the period thereafter. 3 D reconstructions of the image data were created for clinical diagnostics and planning of interventions. Image quality was assessed using a 4-point-scale. The visibility of the mammary arteries was analyzed, and signal-to-noise-ratio (SNR) and contrast-to-noise-ratio (CNR) were calculated. The usefulness of 3D reconstructions for surgical planning was rated using a 5-point-scale. Radiation exposure and contrast dye consumption were determined. All cases were analyzed retrospectively. RESULTS: DSCT was successfully used in 118 cases. All image data obtained were interpretable. More than 60 percent of cases did not show any artifacts. The mammary arteries were visible down to the diaphragmatic arch in more than 80 percent of cases. Diagnostic value and surgical benefit were evaluated as "useful" or as "essential" in all cases. Median radiation dose was 0.4 mSv and 0.27 mSv for the 2nd and 3 rd generation DSCT, respectively. Consumption of contrast dye was 2 ml/kg in all cases. CONCLUSION: DSCT is a modern and extremely helpful technique for diagnostics and planning of interventions in patients with complex congenital heart defects. Extracardiac vascular structures in particular can be depicted three-dimensionally at high resolution. The use of iterative reconstruction with 3 rd generation DSCT yielded image quality similar to that of 2nd generation DSCT at considerably reduced radiation exposure level compared to 2nd generation DSCT. 3 rd generation DSCT is a low risk, accurate and extremely fast technique for diagnosing unstable patients with CHD. KEY POINTS: Expanded scope of indications for DSCT in diagnosing critically ill infants. Effective radiation dose is considerably lower than 0.5 mSv. Extremely rapid image acquisitions with high image quality. Possibility of optimized 3D-based surgical planning PMID- 26815125 TI - [04. - 07. May 2016 - member assembly at the 97th German Roentgen Congress]. PMID- 26815127 TI - [Roentgen Academy - first basic course in leadership competence for radiologists in Berlin]. PMID- 26815128 TI - [Physician's patient education obligation in diagnostic radiography]. PMID- 26815129 TI - [The BDR invites - specialty excursion for radiologists to the "Central Kingdom" of Peking]. PMID- 26815130 TI - A 55-Year-Old Man With Periorbital and Inguinal Masses, Pericarditis, and Pleuritis. PMID- 26815131 TI - Next-Generation Sequencing Reveals Restriction and Clonotypic Expansion of Treg Cells in Juvenile Idiopathic Arthritis. AB - OBJECTIVE: Treg cell-mediated suppression of Teff cells is impaired in juvenile idiopathic arthritis (JIA); however, the basis for this dysfunction is incompletely understood. Animal models of autoimmunity and immunodeficiency demonstrate that a diverse Treg cell repertoire is essential to maintain Treg cell function. The present study was undertaken to investigate the Treg and Teff cell repertoires in JIA. METHODS: Treg cells (CD4+CD25+CD127(low) ) and Teff cells (CD4+CD25-) were isolated from peripheral blood and synovial fluid obtained from JIA patients, healthy controls, and children with Lyme arthritis. Treg cell function was measured in suppressive assays. The T cell receptor beta chain (TRB) was amplified by multiplex polymerase chain reaction and next-generation sequencing was performed, with amplicons sequenced using an Illumina HiSeq platform. Data were analyzed using ImmunoSEQ, International ImMunoGeneTics system, and the Immunoglobulin Analysis Tools. RESULTS: Compared to findings in controls, the JIA peripheral blood Treg cell repertoire was restricted, and clonotypic expansions were found in both blood and synovial fluid Treg cells. Skewed usage and pairing of TRB variable and joining genes, including overuse of gene segments that have been associated with other autoimmune conditions, was observed. JIA patients shared a substantial portion of synovial fluid Treg cell clonotypes that were private to JIA and not identified in Lyme arthritis. CONCLUSION: We identified restriction and clonotypic expansions in the JIA Treg cell repertoire with sharing of Treg cell clonotypes across patients. These findings suggest that abnormalities in the Treg cell repertoire, possibly engendered by shared antigenic triggers, may contribute to disease pathogenesis in JIA. PMID- 26815133 TI - Inverse Charge Transfer in the Quadruple Perovskite CaCu3Fe4O12. AB - Structural and spectroscopic analyses revealed that the quadruple perovskite CaCu3Fe4O12 undergoes an "inverse" electron charge transfer in which valence electrons move from B-site Fe to A'-site Cu ions (~3Cu(~2.4+) + 4Fe(~3.65+) -> ~3Cu(~2.2+) + 4Fe(~3.8+)) simultaneously with a charge disproportionation transition (4Fe(~3.8+) -> ~2.4Fe(3+) + ~1.6Fe(5+)), on cooling below 210 K. The direction of the charge transfer for CaCu3Fe4O12 is opposite to those reported for other perovskite oxides such as BiNiO3 and ACu3Fe4O12 (A = Sr(2+) or the large trivalent rare-earth metal ions), in which the electrons move from A/A' site to B-site ions. This finding sheds a light on a new aspect in intermetallic phenomena for complex transition metal compounds. PMID- 26815132 TI - Successful delivery of polytetrafluoroethylene-covered stent using rapid exchange guide extension catheter. AB - Deployment of polytetrafluoroethylene (PTFE)-covered stent is a useful technique to seal coronary perforation. However, the high profile and low flexibility compromise its deliverability. To facilitate stent delivery, a guide extension catheter (GuideLinerTM catheter) through a 6 Fr guiding catheter has been used. This case report describes a successful deployment of a PTFE-covered stent using a 6 Fr GuideLiner catheter to seal coronary perforation. PMID- 26815134 TI - Complex chromosomal rearrangements leading to MECOM overexpression are recurrent in myeloid malignancies with various 3q abnormalities. AB - Chromosomal rearrangements involving 3q26 are recurrent findings in myeloid malignancies leading to MECOM overexpression, which has been associated with a very poor prognosis. Other 3q abnormalities have been reported and cryptic MECOM rearrangements have been identified in some cases. By fluorescence in situ hybridization (FISH) analysis, we investigated 97 acute myeloid leukemia/myelodysplastic syndrome patients with various 3q abnormalities to determine the role and the frequency of the involvement of MECOM. We identified MECOM rearrangements in 51 patients, most of them showed 3q26 involvement by chromosome banding analysis (CBA): inv(3)/t(3;3) (n = 26) and other balanced 3q26 translocations (t(3q26)) (n = 15); the remaining cases (n = 10) showed various 3q abnormalities: five with balanced translocations involving 3q21 or 3q25; two with homogenously staining region (hsr) on 3q; and three with other various 3q abnormalities. Complex rearrangements with multiple breakpoints on 3q, masking 3q26 involvement, were identified in cases with 3q21/3q25 translocations. Furthermore, multiple breaks were observed in two cases with t(3q26), suggesting that complex rearrangement may also occur in apparently simple t(3q26). Intrachromosomal gene amplification was another mechanism leading to MECOM overexpression in two cases with hsr on 3q. In the last three cases, FISH analysis revealed 3q26 involvement that was missed by CBA because of metaphases' suboptimal quality. All cases with MECOM rearrangements showed overexpression by real-time quantitative PCR. Finally, MECOM rearrangements can occur in patients with 3q abnormalities even in the absence of specific 3q26 involvement, underlining that their frequency is underestimated. As MECOM rearrangement has been associated with very poor prognosis, its screening should be performed in patients with any 3q abnormalities. PMID- 26815135 TI - Research Needs and Challenges Regarding Palliation for Individuals in Long-Term Care Settings. PMID- 26815136 TI - Aging in Community: Developing a More Holistic Approach to Enhance Older Adults' Well-Being. AB - Public health advances have contributed to increased longevity; however, individuals are more likely to live longer with multiple chronic conditions. The existing health care system primarily focuses on treating disease rather than addressing well-being as a holistic construct that includes physical, social, and environmental components. The current commentary emphasizes the importance of supporting healthy active aging and aging in community. The barriers to aging in community and the state of the intervention science in response to this problem are discussed, and recommendations for future research are provided. Active aging is more than managing illness or care transitions-it promotes engagement, participation, dignity, self-fulfillment, self-determination, and support for older adults. To support aging in community and healthy active aging, a paradigm shift is needed in how the well-being of older adults is thought about and supported. PMID- 26815137 TI - Response to the Commentary: Aging in Community. PMID- 26815139 TI - Maternal obesity associated with increase in natural killer T cells and CD8+ regulatory T cells in cord blood units. AB - BACKGROUND: One of the major limitations of umbilical cord blood (UCB) as hematopoietic stem cell source is its restricted cell number. In mothers who are candidates for stem cell donation, there are variables that affect the quantity and quality of UCB units. The aim of this study was to determine if obstetric, maternal, and fetal factors modify the number of lymphocyte subsets in UCB units. STUDY DESIGN AND METHODS: This was a prospective, observational study. In UCB units, the numbers of CD34, NK, NKT, iNKT, Type 1 dendritic cells (DCs), Type 2 DCs, T gammadelta, T CD4+, T CD8+ lymphocytes, CD4+CD25+FoxP3+, and CD8+CD25+FoxP3+ T regulatory (Treg) cells were quantified by flow cytometry. RESULTS: Fifty-four UCB units were included; the donors' mean weight was 75 kg (range, 52 to 102 kg) and they had a mean body mass index (BMI) of 30 kg/m(2) (range 22 to 40 kg/m(2) ), of which 12 (22%) had a normal BMI, 14 (26%) were overweight, and 28 (52%) were obese. The mean number of CD34+ cells was 4.45 * 10(6) (range, 0.7 * 10(6) to 20.5 * 10(6) ). The number of NKT, CD3+, CD4+, CD8+, and CD8+CD25+FoxP3+ Treg cells was significantly higher in overweight or obese mothers; CD34+ cells were decreased in the same group. The number of iNKT and CD34+ cells was decreased in newborns weighing above the average. CONCLUSIONS: Maternal factors such as BMI, and fetal factors such as weight at birth, should be added to the selection criteria of UCB donors. PMID- 26815141 TI - Nicking endonuclease-assisted recycling of target-aptamer complex for sensitive electrochemical detection of adenosine triphosphate. AB - An electrochemical biosensor was developed for the detection of adenosine triphosphate (ATP) based on target-induced conformation switching and nicking endonuclease (NEase)-assisted signal amplification. The electrochemical biosensor was constructed by base pairing and target recognition. After capture DNA hybridized with the gold electrode, a significant current of Methylene Blue (MB) was obtained by differential pulse voltammetry. In the presence of ATP, the hairpin DNA formed a G-quadruplex structure due to the specific recognition between hairpin DNA and ATP. Then the exposed part of the target-aptamer complex hybridized with the 3'-terminus of capture DNA to form a specific nicking site for Nb.BbvCI, which led to NEase-assisted target-aptamer complex recycling. The released target-aptamer complex hybridized with the remaining capture DNA. Nb.BbvCI-assisted target-aptamer complex recycling caused the continuous cleavage of capture DNA with MB at its 5'-terminus, resulting in release of a certain amount of DNA fragment labeled with MB. Then the current value decreased significantly. The reduced current showed a linear range from 10 nM to 1 MUM with a limit of detection as low as 3.4 nM. Furthermore, the proposed strategy can be used for the detection of similar substances. PMID- 26815140 TI - Effects of copper particles on a model septic system's function and microbial community. AB - There is concern surrounding the addition of nanoparticles into consumer products due to toxicity potential and the increased risk of human and environmental exposures to these particles. Copper nanoparticles are found in many common consumer goods; therefore, the disposal and subsequent interactions between potentially toxic Cu-based nanoparticles and microbial communities may have detrimental impacts on wastewater treatment processes. This study investigates the effects of three copper particles (micron- and nano-scale Cu particles, and a nano-scale Cu(OH)2-based fungicide) on the function and operation of a model septic tank. Septic system analyses included water quality evaluations and microbial community characterizations to detect changes in and relationships between the septic tank function and microbial community phenotype/genotype. As would be expected for optimal wastewater treatment, biological oxygen demand (BOD5) was reduced by at least 63% during nano-scale Cu exposure, indicating normal function. pH was reduced to below the optimum anaerobic fermentation range during the micro Cu exposure, suggesting incomplete degradation of organic waste may have occurred. The copper fungicide, Cu(OH)2, caused a 57% increase in total organic carbon (TOC), which is well above the typical range for septic systems and also corresponded to increased BOD5 during the majority of the Cu(OH)2 exposure. The changes in TOC and BOD5 demonstrate that the system was improperly treating waste. Overall, results imply individual exposures to the three Cu particles caused distinct disruptions in septic tank function. However, it was observed that the system was able to recover to typical operating conditions after three weeks post-exposure. These results imply that during periods of Cu introduction, there are likely pulses of improper removal of total organic carbon and significant changes in pH not in the optimal range for the system. PMID- 26815142 TI - Kinetic Characterization of 100 Glycoside Hydrolase Mutants Enables the Discovery of Structural Features Correlated with Kinetic Constants. AB - The use of computational modeling algorithms to guide the design of novel enzyme catalysts is a rapidly growing field. Force-field based methods have now been used to engineer both enzyme specificity and activity. However, the proportion of designed mutants with the intended function is often less than ten percent. One potential reason for this is that current force-field based approaches are trained on indirect measures of function rather than direct correlation to experimentally-determined functional effects of mutations. We hypothesize that this is partially due to the lack of data sets for which a large panel of enzyme variants has been produced, purified, and kinetically characterized. Here we report the kcat and KM values of 100 purified mutants of a glycoside hydrolase enzyme. We demonstrate the utility of this data set by using machine learning to train a new algorithm that enables prediction of each kinetic parameter based on readily-modeled structural features. The generated dataset and analyses carried out in this study not only provide insight into how this enzyme functions, they also provide a clear path forward for the improvement of computational enzyme redesign algorithms. PMID- 26815143 TI - Different Sets of Post-Embryonic Development Genes Are Conserved or Lost in Two Caryophyllales Species (Reaumuria soongorica and Agriophyllum squarrosum). AB - Reaumuria soongorica and sand rice (Agriophyllum squarrosum) belong to the clade of Caryophyllales and are widely distributed in the desert regions of north China. Both plants have evolved many specific traits and adaptation strategies to cope with recurring environmental threats. However, the genetic basis that underpins their unique traits and adaptation remains unknown. In this study, the transcriptome data of R. soongorica and sand rice were compared with three other species with previously sequenced genomes (Arabidopsis thaliana, Oryza sativa, and Beta vulgaris). Four different gene sets were identified, namely, the genes conserved in both species, those lost in both species, those conserved in R. soongorica only, and those conserved in sand rice only. Gene ontology showed that post-embryonic development genes (PEDGs) were enriched in all gene sets, and different sets of PEDGs were conserved or lost in both the R. soongorica and sand rice genomes. Expression profiles of Arabidopsis orthologs further provided some clues to the function of the species-specific conserved PEDGs. Such orthologs included LEAFY PETIOLE, which could be a candidate gene involved in the development of branch priority in sand rice. PMID- 26815144 TI - The importance of determining the limit of detection of non-invasive prenatal testing methods. AB - OBJECTIVE: Several non-invasive prenatal testing (NIPT) methods, which analyze circulating fetal cell-free DNA (cfDNA) in maternal plasma, suggest a fetal fraction (FF) >= 4% for a reportable result, with the assumption that fetal aneuploidies may not be detectable at lower FF. This study determined the actual limit of detection (LOD) of a massively parallel sequencing-based NIPT method and evaluated its performance in testing samples with low FF. METHOD: An experimental model, involving the creation of artificial plasma mixtures with a final aneuploid FF ranging from 1% to 4%, simulated samples at different proportions of fetal cfDNA. We then analyzed 7103 blood samples, from pregnant women undergoing NIPT, to assess the impact of low FF on the performance of cfDNA testing. RESULTS: Detection of common aneuploidies in samples with an FF as low as 2% is well within the ability of this technology. Of 105 pregnancies confirmed chromosomally abnormal, 25 (23.8%) involving a 2% < FF < 4% were consistently detected. These high-risk pregnancies would have not been identified using the suggested 4% FF cut-off. CONCLUSION: This study underscores the importance of determining the actual LOD for each specific NIPT methodology. It may reduce the incidence of test cancelations and shorten the time required for the diagnosis of aneuploidy. (c) 2016 John Wiley & Sons, Ltd. PMID- 26815145 TI - Update on the Diagnosis and Management of Colon Ischemia. AB - OPINION STATEMENT: Colonic ischemia is the most common ischemic disorder of the gastrointestinal tract. The condition occurs more commonly in women, and risk increases with advancing age. Presenting symptoms include abdominal pain, bowel urgency, and passage of bloody diarrhea; however, nearly one half of patients do not present with this classic triad of symptoms. Abdominal pain without bloody diarrhea or non-bloody diarrhea should raise concern for an isolated right colon pattern of ischemia. An isolated right colon distribution is associated with more severe outcomes, including need for surgical intervention and increased mortality. Patients that present with symptoms concerning for ischemia should undergo computed tomography (CT) scan of the abdomen and pelvis with oral and IV contrast and laboratory testing. Colonoscopy should be performed in patients without evidence of peritonitis. Medical history should be obtained to identify possible etiologies of ischemia. Thrombophilia workup should be considered in young patients and those with recurrent ischemia, but is not required universally. In cases of isolated right colon ischemia, evaluation of the mesenteric vasculature is particularly important, for exclusion of concurrent acute mesenteric ischemia. Treatment of ischemic colitis is supportive in less severe cases, with intravenous fluids and bowel rest. Broad-spectrum antibiotics should be initiated, and surgical consultation should be obtained in cases of severe disease, pancolonic ischemia, and isolated right colonic ischemia. Surgery should be performed for peritonitis, hemodynamic instability, or failure of non operative management. This article will review colonic ischemia diagnosis, evaluation, and treatment. PMID- 26815147 TI - Novel Effective Catalyst for Elemental Mercury Removal from Coal-Fired Flue Gas and the Mechanism Investigation. AB - Mercury pollution from coal-fired power plants has drawn attention worldwide. To achieve efficient catalytic oxidation of Hg(0) at both high and low temperatures, we prepared and tested novel IrO2 modified Ce-Zr solid solution catalysts under various conditions. It was found that the IrO2/Ce0.6Zr0.4O2 catalyst, which was prepared using the polyvinylpyrrolidone-assisted sol-gel method, displayed significantly higher catalytic activity for Hg(0) oxidation. The mechanism of Hg(0) removal over IrO2/Ce0.6Zr0.4O2 was studied using various methods, and the Hg(0) oxidation reaction was found to follow two possible pathways. For the new chemisorption-regeneration mechanism proposed in this study, the adsorbed Hg(0) was first oxidized with surface chemisorbed oxygen species to form HgO; the HgO could desorb from the surface of catalysts by itself or react with adsorbed HCl to be release in the form of gaseous HgCl2. O2 is indispensable for the chemisorption process, and the doping of IrO2 could facilitate the chemisorption process. In addition, the Deacon reaction mechanism was also feasible for Hg(0) oxidation: this reaction would involve first oxidizing the adsorbed HCl to active Cl species, after which the Hg(0) could react with Cl to form HgCl2. Additionally, doping IrO2 could significantly improve the Cl yield process. In summary, the novel IrO2 modified catalyst displayed excellent catalytic activity for elemental mercury oxidation, and the proposed reaction mechanisms were determined reasonably. PMID- 26815148 TI - The Relationship Of Personality Structure To Patterns Of Adolescent Substance Use. AB - The relationship of personality to patterns of adolescent substance use was examined in an effort to determine the extent to which these domains overlap. During the first year of a longitudinal study of adolescent drug use, self-report data were collected on personality and current use patterns of 13 substances. The data from the domains of drug use and personality were interrelated using canonical correlation analysis. Rotation of canonical variates and cross validation were used in order to distinguish between statistically significant and theoretically meaningful results. The results revealed that a single dimension of general substance use was associated with a cluster of personality traits and attitudes. Although the overlap between the drug use and personality domains was moderately high, the ability of personality to account for variations in adolescent substance use was relatively low. PMID- 26815149 TI - Identifying Interindividual Judgment Differences: Indscal Or Three-Mode Factor Analysis? AB - Seventy subjects judged 9 key-politicians of the German parliamentary scene on 22 bipolar seven-point attribute scales. Profile similarities were computed for each possible stimulus pair separately for each individual. The resulting proximity matrices were analyzed with "INDSCAL." Additionally, three-mode factor analysis was applied to the original three-way data matrix. The results of the two methods are compared. Special attention is given to the problem of how interindividual judgment differences are reflected by the individual parameters of the two models; these are the INDSCAL-weights and the factor scores of an extended core matrix. The results suggest that three-mode factor analysis is more suitable, if interindividual judgment differences are to be described by means of a spatial model. PMID- 26815146 TI - An adaptive immune response driven by mature, antigen-experienced T and B cells within the microenvironment of oral squamous cell carcinoma. AB - Lymphocyte infiltrates have been observed in the microenvironment of oral cancer; however, little is known about whether the immune response of the lymphocyte infiltrate affects tumor biology. For a deeper understanding of the role of the infiltrating-lymphocytes in oral squamous cell carcinoma (OSCC), we characterized the lymphocyte infiltrate repertoires and defined their features. Immunohistochemistry revealed considerable T and B cell infiltrates and lymphoid follicles with germinal center-like structures within the tumor microenvironment. Flow cytometry demonstrated that populations of antigen-experienced CD4+ and CD8+ cells were present, as well as an enrichment of regulatory T cells; and T cells expressing programmed death-1 (PD-1) and T cell Ig and mucin protein-3 (Tim-3), indicative of exhaustion, within the tumor microenvironment. Characterization of tumor-infiltrating B cells revealed clear evidence of antigen exposure, in that the cardinal features of an antigen-driven B cell response were present, including somatic mutation, clonal expansion, intraclonal variation and isotype switching. Collectively, our results point to an adaptive immune response occurring within the OSCC microenvironment, which may be sustained by the expression of specific antigens in the tumor. PMID- 26815150 TI - Interrelations Among Models For The Analysis Of Moment Structures. AB - Factor analysis in several populations, covariance structure models, three-mode factor analysis, structural equation systems with measurement model, and analysis of covariance with measurement model are all shown to be specializations of a general moment structure model published previously in this journal. Some new structured linear models are also described; they may be considered either generalizations or special cases of existing models. Simple representations are developed for complex linear models, and some applications to behavioral data are cited. PMID- 26815151 TI - Using Internal Inconsistency To Identify Unreliable Ratings. AB - This paper describes the development and testing of an internal inconsistency scale to help identify unreliable clinical ratings. The scale consists of pairs of logically inconsistent items which have been chosen and scored using a combination of rational and statistical procedures. Evidence is presented to indicate that the scale measures rater inconsistencies rather than patient "inconsistencies," that using inconsistency scores to eliminate unreliable ratings improves factor score reliabilities, and that increasing the number of items for random assignment of possible rating values systematically increases the inconsistency score. Although the inconsistency scale was constructed specifically for the Missouri Inpatient Behavior Scale (MIBS), the methodology is potentially applicable to other rating scales. PMID- 26815152 TI - Confirmatory Factor Analysis Applications: Missing Data Problems And Comparison Of Path Models Between Populations. AB - Procedures for simultaneous confirmatory factor analysis in several populations are useful in a wide variety of problems. This is demonstrated with examples involving missing data, comparison of part correlations between groups, testing the equality of regression weights between groups with multiple indicators of each variable, and the formulation of growth models. Corrections for attenuation can be incorporated into analysis of covariance and analysis of variance procedures. PMID- 26815153 TI - A Comparison Of The Adjective Check List, Bem Sex Role Inventory, And Personal Attributes Questionnaire Masculinity And Femininity Subscales. AB - Ninety-two male and 131 female undergraduate psychology students were administered the Adjective Check List (ACL), Bem Sex Role Inventory (BSRI), and Personal Attributes Questionnaire (PAQ). The masculinity (M) and femininity (F) subscale scores for each of these three measures were correlated and subjected to a principal factor analysis with varimax rotation separately for males and females. Results indicated that: (1) the ACL-F shared only a modest amount of variance with the BSRI and PAQ-F subscales, and was not responded to in the same manner by males and females; (2) the ACL-M subscale tended to be more strongly negatively related to F subscales than did the BSRI and PAQ-M subscales; (3) the BSRI and PAQ-M and F subscales shared a substantial proportion of variance between themselves, for both males and females; and (4) a masculine factor and a feminine factor, accounting for approximately the same amount of the entire common variance, emerged for both males and females. PMID- 26815154 TI - Multidimensional Scaling Of Derived Dissimilarities. AB - In past research, a matrix of squared profile distances, delta, has sometimes been multidimensionally scaled rather than the matrix of original dissimilarities, D. It is thought that scaling solutions derived from delta have lower stress and enhanced interpretability when applied to data generated by sorting. Two experiments were performed to investigate the consequences of the delta transformation. First, random numbers resembling data collected by the method of sorting were simulated. Scaling solutions derived from delta matrices invariably had lower stress than solutions computed from the associated D matrices. This result suggests that the delta transformation may reduce stress irrespective of any change in interpretability. Simulated dissimilarity matrices were then generated from known stimulus configurations. It was found that: (1) nonmetric multidimensional scaling solutions for delta matrices had relatively lower stress; but under low error conditions (2) solution based on D were more closely related to the underlying configurations; and (3) determination of dimensionality by inspection of the stress plot was somewhat more difficult for solutions based on delta. These results can be understood by observing that the delta transformation tends to increase the size of large distances in the derived configurations relative to small distances. PMID- 26815155 TI - The Utility Of WISC-R Subtest Scores In Discriminating Among Adequate And Underachieving Children. AB - This investigation analyzed the discriminatory or diagnostic utility of using WISC-R subtest scores in differentiating between groups of statistically defined underachieving children and a group of children who were adequately achieving. The sample consisted of 206 children (134 boys, 72 girls) referred for psychological evaluations by their classroom teachers. The results suggested that while underachieving and adequately achieving groups of children can be separated by subtest differences on the WISC-R, the use of derived classification equations from group statistics in individual diagnosis leads to dramatic levels of misclassifications among underachieving students. PMID- 26815156 TI - On Generalizations Of The G Index And The Phi Coefficient To Nominal Scales. AB - If the same categories are used for two nominal scale variables, this information should be used in similarity measures between those variables. Two such similarity measures, one proposed by Goodman & Kruskal and one (kappa) by Cohen, are examined. Two alternative coefficients, called C and S are further proposed. They are found to be generalizations of the G index and the phi coefficient respectively. Both of them seem to have many desirable characteristics, e.g., they are both E-coefficients. They may also be used as measures of similarity between persons classifying into categories defined beforehand. PMID- 26815157 TI - Raking A Garden Factor Solution. AB - In this article some of the causes of matrix singularity are discussed. A relatively simple multivariate procedure is developed to study the variable structure of singular data. This procedure, referred to as data raking, identifies the variable(s) causing singularity. Once identified the variable(s) may be eliminated from the data resulting in the desired non-singular data set that is usually assumed by most multivariate procedures. The logic of the procedure is clarified with illustrative examples using both singular and non singular data. PMID- 26815158 TI - Substrate-Triggered Exosite Binding: Synergistic Dendrimer/Folic Acid Action for Achieving Specific, Tight-Binding to Folate Binding Protein. AB - Polymer-ligand conjugates are designed to bind proteins for applications as drugs, imaging agents, and transport scaffolds. In this work, we demonstrate a folic acid (FA)-triggered exosite binding of a generation five poly(amidoamine) (G5 PAMAM) dendrimer scaffold to bovine folate binding protein (bFBP). The protein exosite is a secondary binding site on the protein surface, separate from the FA binding pocket, to which the dendrimer binds. Exosite binding is required to achieve the greatly enhanced binding constants and protein structural change observed in this study. The G5Ac-COG-FA1.0 conjugate bound tightly to bFBP, was not displaced by a 28-fold excess of FA, and quenched roughly 80% of the initial fluorescence. Two-step binding kinetics were measured using the intrinsic fluorescence of the FBP tryptophan residues to give a KD in the low nanomolar range for formation of the initial G5Ac-COG-FA1.0/FBP* complex, and a slow conversion to the tight complex formed between the dendrimer and the FBP exosite. The extent of quenching was sensitive to the choice of FA-dendrimer linker chemistry. Direct amide conjugation of FA to G5-PAMAM resulted in roughly 50% fluorescence quenching of the FBP. The G5Ac-COG-FA, which has a longer linker containing a 1,2,3-triazole ring, exhibited an ~80% fluorescence quenching. The binding of the G5Ac-COG-FA1.0 conjugate was compared to poly(ethylene glycol) (PEG) conjugates of FA (PEGn-FA). PEG2k-FA had a binding strength similar to that of FA, whereas other PEG conjugates with higher molecular weight showed weaker binding. However, no PEG conjugates gave an increased degree of total fluorescence quenching. PMID- 26815159 TI - Interferon-gamma, but Not Interleukin-4, Suppresses Experimental Polymyositis. AB - OBJECTIVE: C protein-induced myositis (CIM) is a mouse model of polymyositis in which activated antigen-specific CD8+ T cells injure the muscles. Animal models of autoimmunity that have been examined in the past for the effects of the type 1 cytokine interferon-gamma (IFNgamma) and the type 2 cytokine interleukin-4 (IL-4) are all mediated by pathogenic CD4+ T cells. In those models, the disruption of IFNgamma leads to up-regulation of IL-17A, exacerbating the disease with neutrophil infiltration into sites of inflammation. This study was undertaken to investigate the roles of IFNgamma and IL-4, as well as IL-17A in the absence of IFNgamma, in CD8+ T cell-mediated CIM. METHODS: IFNgamma(-/-) mice, anti-IL-17A antibody-treated IFNgamma(-/-) mice, IFNgamma(-/-) IL-17A(-/-) mice, IL-4(-/-) mice, and wild-type C57BL/6 mice were immunized with skeletal muscle C protein fragments to induce CIM. Muscle tissue specimens were examined histologically. RESULTS: IFNgamma(-/-) mice developed myositis at a higher incidence and with greater severity than wild-type mice. Unlike wild-type mice, IFNgamma(-/-) mice had infiltration of neutrophils into the endomysial sites of the affected muscles. IFNgamma(-/-) mice treated with anti-IL-17A antibodies and IFNgamma(-/-) IL-17A(-/-) mice developed myositis with an incidence and severity comparable to those in IFNgamma(-/-) mice and showed neutrophil infiltration similar to that in IFNgamma(-/-) mice. IL-4(-/-) mice developed CIM comparable to that in wild-type mice. CONCLUSION: Our findings indicate that IFNgamma, but not IL-4, plays a suppressive role in the development of CIM. Unlike in CD4+ T cell-mediated autoimmune disease models, IFNgamma prevents factors other than IL-17A from exacerbating myositis and neutrophil infiltration in CD8+ T cell-mediated CIM. PMID- 26815160 TI - Content validity and reliability of test of gross motor development in Chilean children. AB - OBJECTIVE: To validate a Spanish version of the Test of Gross Motor Development (TGMD-2) for the Chilean population. METHODS: Descriptive, transversal, non experimental validity and reliability study. Four translators, three experts and 92 Chilean children, from five to 10 years, students from a primary school in Santiago, Chile, have participated. The Committee of Experts has carried out translation, back-translation and revision processes to determine the translinguistic equivalence and content validity of the test, using the content validity index in 2013. In addition, a pilot implementation was achieved to determine test reliability in Spanish, by using the intraclass correlation coefficient and Bland-Altman method. We evaluated whether the results presented significant differences by replacing the bat with a racket, using T-test. RESULTS: We obtained a content validity index higher than 0.80 for language clarity and relevance of the TGMD-2 for children. There were significant differences in the object control subtest when comparing the results with bat and racket. The intraclass correlation coefficient for reliability inter-rater, intra rater and test-retest reliability was greater than 0.80 in all cases. CONCLUSIONS: The TGMD-2 has appropriate content validity to be applied in the Chilean population. The reliability of this test is within the appropriate parameters and its use could be recommended in this population after the establishment of normative data, setting a further precedent for the validation in other Latin American countries. PMID- 26815161 TI - Therapeutic itineraries and explanations for tuberculosis: an indigenous perspective. AB - OBJECTIVE: To analyze explanations for tuberculosis and therapeutic itineraries of Brazilian indigenous people. METHODS: Case study with a qualitative descriptive approach. We conducted semi-structured interviews with 11 Munduruku indigenous, including direct observation of treatment for tuberculosis in the municipality of Jacareacanga, south-western region of the state of Para, Brazil. To identify explanations for tuberculosis and therapeutic itineraries, we performed thematic content analysis. RESULTS: Traditional medicine was the first therapeutic option chosen by the indigenous. However, biomedicine was also employed, which indicates a circulation between different therapeutic contexts and health concepts among the Munduruku. The explanations provided ranged from recognition of the signs and symptoms specific to tuberculosis to the attribution of the disease to a spirit that leaves the body and wanders in the woods, returning ill into the body. Unlike the biomedical model, which links tuberculosis transmission strictly to interpersonal contact, in closed spaces without natural lighting and ventilation (preferably domestic environments), the Munduruku associate the disease to an indirect contact between people socially distant (enemies or adversaries) in public and open places. CONCLUSIONS: The explanations made by the indigenous are unique and deserve the attention of those who are responsible for developing health public policies, as well as of the teams who work on the villages. To guarantee an efficient control of tuberculosis in these regions, it is necessary that the developed actions integrate biomedicine knowledge and the traditional medicine of the indigenous people, in addition to respecting and welcoming local culture manifestations. PMID- 26815162 TI - Advances and challenges in oral health after a decade of the "Smiling Brazil" Program. AB - OBJECTIVE: To analyze oral health work changes in primary health care after Brazil's National Oral Health Policy Guidelines were released. METHODS: A literature review was conducted on Medline, LILACS, Embase, SciELO, Biblioteca Virtual em Saude, and The Cochrane Library databases, from 2000 to 2013, on elements to analyze work changes. The descriptors used included: primary health care, family health care, work, health care policy, oral health care services, dentistry, oral health, and Brazil. Thirty-two studies were selected and analyzed, with a predominance of qualitative studies from the Northeast region with workers, especially dentists, focusing on completeness and quality of care. RESULTS: Observed advances focused on educational and permanent education actions; on welcoming, bonding, and accountability. The main challenges were related to completeness; extension and improvement of care; integrated teamwork; working conditions; planning, monitoring, and evaluation of actions; stimulating people's participation and social control; and intersectorial actions. CONCLUSIONS: Despite the new regulatory environment, there are very few changes in oral health work. Professionals tend to reproduce the dominant biomedical model. Continuing efforts will be required in work management, training, and permanent education fields. Among the possibilities are the increased engagement of managers and professionals in a process to understand work dynamics and training in the perspective of building significant changes for local realities. PMID- 26815164 TI - Enhanced Conversion Efficiency of Cu(In,Ga)Se2 Solar Cells via Electrochemical Passivation Treatment. AB - Defect control in Cu(In,Ga)Se2 (CIGS) materials, no matter what the defect type or density, is a significant issue, correlating directly to PV performance. These defects act as recombination centers and can be briefly categorized into interface recombination and Shockley-Read-Hall (SRH) recombination, both of which can lead to reduced PV performance. Here, we introduce an electrochemical passivation treatment for CIGS films that can lower the oxygen concentration at the CIGS surface as observed by X-ray photoelectron spectrometer analysis. Temperature-dependent J-V characteristics of CIGS solar cells reveal that interface recombination is suppressed and an improved rollover condition can be achieved following our electrochemical treatment. As a result, the surface defects are passivated, and the power conversion efficiency performance of the solar cell devices can be enhanced from 4.73 to 7.75%. PMID- 26815163 TI - Activating mutations in CTNNB1 in aldosterone producing adenomas. AB - Primary aldosteronism (PA) is the most common cause of secondary hypertension with a prevalence of 5-10% in unreferred hypertensive patients. Aldosterone producing adenomas (APAs) constitute a large proportion of PA cases and represent a surgically correctable form of the disease. The WNT signaling pathway is activated in APAs. In other tumors, a frequent cause of aberrant WNT signaling is mutation in the CTNNB1 gene coding for beta-catenin. Our objective was to screen for CTNNB1 mutations in a well-characterized cohort of 198 APAs. Somatic CTNNB1 mutations were detected in 5.1% of the tumors, occurring mutually exclusive from mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. All of the observed mutations altered serine/threonine residues in the GSK3beta binding domain in exon 3. The mutations were associated with stabilized beta-catenin and increased AXIN2 expression, suggesting activation of WNT signaling. By CYP11B2 mRNA expression, CYP11B2 protein expression, and direct measurement of aldosterone in tumor tissue, we confirmed the ability for aldosterone production. This report provides compelling evidence that aberrant WNT signaling caused by mutations in CTNNB1 occur in APAs. This also suggests that other mechanisms that constitutively activate the WNT pathway may be important in APA formation. PMID- 26815165 TI - Two-week test-retest reliability of the Polar(r) RS800CXTM to record heart rate variability. AB - Recently, research has validated the use of Polar(r) heart rate monitors as a tool to index heart rate variability (HRV). In the current investigation, we sought to evaluate the test-retest reliability of both time and frequency domain measures of HRV using the Polar(r) RS800CXTM . Continuous HRV data were collected as 60 nominally healthy adults underwent a resting and orthostatic stress test. We evaluated reproducibility by means of the interclass correlation coefficient for absolute agreement and consistency, and the standard error of measurement. We found moderate reliable 2-week test-retest reliability of HRV using the Polar(r) RS800CXTM , results that are in line with previous studies that have validated the stability of HRV using other methods of measurement (e.g. electrocardiogram). Additionally, when examining different methods of spectral density estimation, we found that using the auto-regressive transformation method provides the most stable indices of HRV. Taken together, our results suggest that the Polar(r) RS800CXTM is not only a valid method to record HRV, but also a reliable one, particularly when using the auto-regressive transformation method. PMID- 26815166 TI - Accessible Method for the Development of Novel Sterol Analogues with Dipeptide like Side Chains That Act as Neuroinflammation Inhibitors. AB - A number of novel sterol derivatives with dipeptide-like side chains were synthesized using an Ugi four-component condensation method and assayed to test their anti-inflammatory effects in activated microglial cells. Compound 18b ((3S,10R,13S)-N-((R)-1-(tert-butylamino)-1-oxo-3-phenylpropan-2-yl)-3-hydroxy N,10,13-trimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H cyclopenta[a]phenanthrene-17-carboxamide) was identified as the most potent anti inflammatory agent in the series of compounds analyzed. Compound 18b markedly inhibited the expression of proinflammatory factors, including inducible nitric oxide synthase, interleukin (IL)-6, IL-1beta, tumor necrosis factor-alpha, and cyclooxygenase-2 in lipopolysaccharide-stimulated microglial cells. Further studies showed that compound 18b significantly suppressed the transcriptional activity of AP-1 and NF-kappaB in activated microglial cells, which was likely mediated by the inhibition of the p38 MAPK and JNK signal transduction pathways. In addition, compound 18b displayed neuroprotective effects in a microglial conditioned medium/neuron coculture and an experimental focal ischemic mouse model. PMID- 26815167 TI - Information and redundancy in the burial folding code of globular proteins within a wide range of shapes and sizes. AB - Recent ab initio folding simulations for a limited number of small proteins have corroborated a previous suggestion that atomic burial information obtainable from sequence could be sufficient for tertiary structure determination when combined to sequence-independent geometrical constraints. Here, we use simulations parameterized by native burials to investigate the required amount of information in a diverse set of globular proteins comprising different structural classes and a wide size range. Burial information is provided by a potential term pushing each atom towards one among a small number L of equiprobable concentric layers. An upper bound for the required information is provided by the minimal number of layers L(min) still compatible with correct folding behavior. We obtain L(min) between 3 and 5 for seven small to medium proteins with 50 <= Nr <= 110 residues while for a larger protein with Nr = 141 we find that L >= 6 is required to maintain native stability. We additionally estimate the usable redundancy for a given L >= L(min) from the burial entropy associated to the largest folding compatible fraction of "superfluous" atoms, for which the burial term can be turned off or target layers can be chosen randomly. The estimated redundancy for small proteins with L = 4 is close to 0.8. Our results are consistent with the above-average quality of burial predictions used in previous simulations and indicate that the fraction of approachable proteins could increase significantly with even a mild, plausible, improvement on sequence-dependent burial prediction or on sequence-independent constraints that augment the detectable redundancy during simulations. PMID- 26815169 TI - Enzalutamide (formerly MDV3100) prolongs survival in docetaxel-pretreated castration-resistant prostate cancer patients. PMID- 26815168 TI - Super-resolution Localization and Defocused Fluorescence Microscopy on Resonantly Coupled Single-Molecule, Single-Nanorod Hybrids. AB - Optical antennas made of metallic nanostructures dramatically enhance single molecule fluorescence to boost the detection sensitivity. Moreover, emission properties detected at the optical far field are dictated by the antenna. Here we study the emission from molecule-antenna hybrids by means of super-resolution localization and defocused imaging. Whereas gold nanorods make single-crystal violet molecules in the tip's vicinity visible in fluorescence, super-resolution localization on the enhanced molecular fluorescence reveals geometrical centers of the nanorod antenna instead. Furthermore, emission angular distributions of dyes linked to the nanorod surface resemble that of nanorods in defocused imaging. The experimental observations are consistent with numerical calculations using the finite-difference time-domain method. PMID- 26815170 TI - Alkaloid Quantities in Endophyte-Infected Tall Fescue are Affected by the Plant Fungus Combination and Environment. AB - Many grass species are symbiotic with systemic, vertically-transmitted, asymptomatic Epichloe endophytic fungi. These fungi often produce alkaloids that defend the host against herbivores. We studied how environmental variables affect alkaloids in endophyte-infected tall fescue (Schedonorus phoenix) from three Northern European wild origins and the widely planted US cultivar 'Kentucky-31' (KY31). The plants were grown in identical common garden experiments in Finland and Kentucky for two growing seasons. Plants were left as controls (C) or given water (W), nutrient (N) or water and nutrient (WN) treatments. For 8-10 replications of each plant origin and treatment combination in both experiments, we analyzed ergot alkaloids, lysergic acid, and lolines. In Finland, tall fescue plants produced 50 % more ergot alkaloids compared to plants of the same origin and treatments in Kentucky. Origin of the plants affected the ergot alkaloid concentration at both study sites: the wild origin plants produced 2-4 times more ergot alkaloids than KY31, but the ergot alkaloid concentration of KY31 plants was the same at both locations. Overall lysergic acid content was 60 % higher in plants grown in Kentucky than in those grown in Finland. Nutrient treatments (N, WN) significantly increased ergot alkaloid concentrations in plants from Finland but not in plants from Kentucky. These results suggest that the success of KY31 in US is not due to selection for high ergot alkaloid production but rather other traits associated with the endophyte. In addition, the environmental effects causing variation in alkaloid production of grass-endophyte combinations should be taken into account when using endophyte-infected grasses agriculturally. PMID- 26815172 TI - Effects of Two Different Weight Training Programs on Swimming Performance and Muscle Enzyme Activities and Fiber Type. AB - The effects of 2 different weight training programs incorporating bench press (BP) and pullover (PO) exercises on swimming performance, power, enzyme activity, and fiber type distribution were studied on 16 men (age = 23 +/- 4 years). A 30 second group (n = 6) performed up to 20 repetitions of BP and PO in 30 seconds. The 2-minute group (n = 6) performed a maximum of 80 repetitions of BP and PO in 2 minutes. As participants reached the prescribed 20 or 80 repetitions, the weight was increased 4.5 kg. A third group (n = 4) served as nontraining controls. Exercise groups trained 3 times per week for 6 weeks. Maximal effort swims of 50 and 200 yd were performed before and after training. Training resulted in increases in work on both exercises in both groups pre- to post training (BP 30 seconds, 722 +/- 236-895 +/- 250 kg; PO 30 seconds, 586 +/- 252 1,090 +/- 677 kg; and BP 2 minutes, 1,530 +/- 414-1,940 +/- 296; PO 2 minutes, 1,212 +/- 406-2,348 +/- 194, p <= 0.05). Swim performances of the 30-second group improved for both the 50-yd (32.0 +/- 6.9 seconds, 30.0 +/- 5.9 seconds, p <= 0.05) and 200-yd swims 200.0 +/- 54 seconds, 182 +/- 45.1 seconds (p <= 0.05), whereas 2-minute training improved only the 200-yd swim (198.3 +/- 32.3 seconds, 186.2 +/- 32.2 seconds). No changes in swim performance were observed for the control group. Triceps muscle succinate dehydrogenase activities increased (pre 3.48 +/- 1.1 MUmol . g(-1) wet weight per minute, post 6.25 +/- 1.5 MUmoles . g( 1) wet weight per minute, p <= 0.05) in only the 30-second training group, whereas phosphofructokinase activities and fiber type distribution did not change in either training group. This study has demonstrated that a 30-second 20 repetition weight training program, specific to the swimming musculature without concurrent swim training, improves swimming performances at both 50- and 200-yd distances. PMID- 26815174 TI - Changes in Adductor Strength After Competition in Academy Rugby Union Players. AB - This study determined the magnitude of change in adductor strength after a competitive match in academy rugby union players and examined the relationship between locomotive demands of match-play and changes in postmatch adductor strength. A within-subject repeated measures design was used. Fourteen academy rugby union players (age, 17.4 +/- 0.8 years; height, 182.7 +/- 7.6 cm; body mass, 86.2 +/- 11.6 kg) participated in the study. Each player performed 3 maximal adductor squeezes at 45 degrees of hip flexion before and immediately, 24, 48, and 72 hours postmatch. Global positioning system was used to assess locomotive demands of match-play. Trivial decreases in adductor squeeze scores occurred immediately (-1.3 +/- 2.5%; effect size [ES] = -0.11 +/- 0.21; likely, 74%) and 24 hours after match (-0.7 +/- 3%; ES = -0.06 +/- 0.25; likely, 78%), whereas a small but substantial increase occurred at 48 hours (3.8 +/- 1.9%; ES = 0.32 +/- 0.16; likely, 89%) before reducing to trivial at 72 hours after match (3.1 +/- 2.2%; ES = 0.26 +/- 0.18; possibly, 72%). Large individual variation in adductor strength was observed at all time points. The relationship between changes in adductor strength and distance covered at sprinting speed (VO2max >= 81%) was large immediately postmatch (p = 0.056, r = -0.521), moderate at 24 hours (p = 0.094, r = -0.465), and very large at 48 hours postmatch (p = 0.005, r = -0.707). Players who cover greater distances sprinting may suffer greater adductor fatigue in the first 48 hours after competition. The assessment of adductor strength using the adductor squeeze test should be considered postmatch to identify players who may require additional rest before returning to field based training. PMID- 26815173 TI - Enhancing Short-Term Recovery After High-Intensity Anaerobic Exercise. AB - This study examined the effects of antioxidant vitamins, ibuprofen, cold water submersion, and whey protein administered simultaneously on short-term recovery. Competitive athletes (n = 22) performed the protocol in 2 occasions (treatment and control) separated by 15 days in counterbalanced crossover design. Each occasion consisted of morning and afternoon sessions (AM and PM). In each session, participants performed 2 bouts of high-intensity anaerobic cycling separated by 30 minutes of rest. Each bout consisted of 3 Wingate tests (3 * 30 second Wingate tests) with 3 minutes of active recovery in between. Power output, rated perceived exertion (RPE), and pain scores were averaged and compared between the 2 sessions (AM vs. PM) and between the treatment vs. control (4 bouts). Creatine kinase (CK) levels were also measured 24 hours after the AM bout. Power output, CK, muscle soreness, and RPE were measured as recovery indices. Creatine kinase increased (p < 0.001) in both treatment and control 24 hours after the AM session. Performance results in the PM session for treatment/control were 832.5 +/- 198.7/813.3 +/- 187.6 W for peak power (PP), and 497.85 +/- 120.7/486.1 +/- 115 W for mean power (MP). Treatment was effective in maintaining MP (p = 0.034) in the PM sessions, but there was no significant effect of treatment on PP (p = 0.193), CK (p = 0.08), pain (p = 0.12), or RPE (p = 0.45). Treatment was helpful in protecting performance, but this was apparently not due to reduced muscle soreness or damage. PMID- 26815171 TI - Nonalcoholic Fatty Liver Disease: Key Considerations Before and After Liver Transplantation. AB - Nonalcoholic fatty liver disease (NAFLD) is the most common etiology of chronic liver disease in developed countries and is on trajectory to become the leading indication for liver transplantation in the USA and much of the world. Patients with NAFLD cirrhosis awaiting liver transplant face unique challenges and increased risk for waiting list stagnation and dropout due to burdensome comorbidities including obesity, diabetes, cardiovascular disease, and kidney disease. Thus far, patients transplanted for NAFLD cirrhosis have excellent mid- and long-term patient and graft survival, but concerns regarding short-term morbidity and mortality continue to exist. Post-liver transplantation, NAFLD occurs as both a recurrent and de novo manifestation, each with unique outcomes. NAFLD in the donor population is of concern given the growing demand for liver transplantation and mounting pressure to expand the donor pool. This review addresses key issues surrounding NAFLD as an indication for transplantation, including its increasing prevalence, unique patient demographics, outcomes related to liver transplantation, development of post-liver transplantation NAFLD, and NAFLD in the liver donor population. It also highlights exciting areas where further research is needed, such as the role of bariatric surgery and preconditioning of marginal donor grafts. PMID- 26815175 TI - Effects of a Simulated Game on Muscle Activation in Youth Baseball Pitchers. AB - It is generally accepted that playing with fatigue is a primary predictor of injury in youth baseball because muscular fatigue is believed to alter mechanics during the arm cocking and acceleration phases. Therefore, the purpose of this study was to quantitatively describe gluteal and upper extremity muscle activations in youth baseball pitchers during a simulated game. Twenty-three youth baseball players (11.2 +/- 0.8 years; 151.4 +/- 8.7 cm; 47.5 +/- 10.8 kg) participated. Data were collected through a Delsys Bagnoli-8-channel electromyography system. Single differential electrodes (interelectrode distance: 10 mm) were attached to the bilateral gluteus maximus and medius and throwing side latissimus dorsi, lower trapezius, and serratus anterior and upper trapezius. After warm-up, participants were instructed to throw randomly provided game situations over a regulation distance (46 feet; 14.02 meters) to a catcher. Three, 4-seam fastballs for strikes, thrown in the first and last innings of the simulated game were selected for analysis. A multivariate analysis of variance revealed no statistically significant differences in muscle activity at the 3 phases of the throw, between first and last innings of the simulated game with an observed power of 0.274 (phase 1: foot contact to maximum shoulder external rotation), 0.297 (phase 2: maximum shoulder external rotation to ball release), and 0.226 (phase 3: ball release to maximum shoulder internal rotation). Examining muscle activations as a pitcher approaches fatigue provides information on how long a pitcher can perform before mechanical alterations occur. Although this study did not reveal significant changes, it did reiterate the fact that pitch counts may be working in possibly preventing a youth pitcher throwing to fatigue. PMID- 26815176 TI - Validity and Reliability of the New Handball-Specific Complex Test. AB - The purpose of this study was to determine the intraobserver reliability (IR) of the handball-specific complex test (HBKT) and the validity of the HBKT and nonspecific tests. Thirty experienced players (25.7 +/- 3.9 years) executed the HBKT twice (time interval: 2 days). Lactate, heart rate (HR), time, throwing velocity and number of errors were measured. Afterwards, players' match performances (MPs) in 30 matches were evaluated using video analysis to compare it with the test parameters. Resting HR between first half and second half (r(2) = 0.26), standing long jump (r(2) = 0.18), jump and reach (r(2) = 0.16), and HR before second half (r(2) = 0.14) were proven to be the most valid tests or parameters. The amounts of explained variance concerning the MP of all other tests/parameters were below 10%. Overall, 41% (12/29) of the parameters showed a high relative intraclass correlation coefficient (ICC > 0.75) and absolute coefficient of variation (CV <= 5%) IR. Results suggest that the HBKT can be certified with an insufficient validity and a sufficient absolute (?CV = 11.3%) and relative (?ICC = 0.67) IR. The reasons could be insufficient tests or insufficient score of MP. The current findings suggest that the coaches and scientists should recognize a lot of effort is necessary to measure MP and to develop valid tests. Additional research should aim to connect test and MP with each other. Before a coach applies a test, he should thoroughly check whether the test is valid (gold standard: MP) and reliable. The frequent and long-term test application (very common argument of the coaches in practice) is not a proof of validity. PMID- 26815177 TI - Validity, Reliability, and Performance Determinants of a New Job-Specific Anaerobic Work Capacity Test for the Norwegian Navy Special Operations Command. AB - Operators in Special Operation Forces (SOF) have a particularly demanding profession where physical and psychological capacities can be challenged to the extremes. The diversity of physical capacities needed depend on the mission. Consequently, tests used to monitor SOF operators' physical fitness should cover a broad range of physical capacities. Whereas tests for strength and aerobic endurance are established, there is no test for specific anaerobic work capacity described in the literature. The purpose of this study was therefore to evaluate the reliability, validity, and to identify performance determinants of a new test developed for testing specific anaerobic work capacity in SOF operators. Nineteen active young students were included in the concurrent validity part of the study. The students performed the evacuation (EVAC) test 3 times and the results were compared for reliability and with performance in the Wingate cycle test, 300-m sprint, and a maximal accumulated oxygen deficit (MAOD) test. In part II of the study, 21 Norwegian Navy Special Operations Command operators conducted the EVAC test, anthropometric measurements, a dual x-ray absorptiometry scan, leg press, isokinetic knee extensions, maximal oxygen uptake test, and countermovement jump (CMJ) test. The EVAC test showed good reliability after 1 familiarization trial (intraclass correlation = 0.89; coefficient of variance = 3.7%). The EVAC test correlated well with the Wingate test (r = -0.68), 300-m sprint time (r = 0.51), and 300-m mean power (W) (r = -0.67). No significant correlation was found with the MAOD test. In part II of the study, height, body mass, lean body mass, isokinetic knee extension torque, maximal oxygen uptake, and maximal power in a CMJ was significantly correlated with performance in the EVAC test. The EVAC test is a reliable and valid test for anaerobic work capacity for SOF operators, and muscle mass, leg strength, and leg power seem to be the most important determinants of performance. PMID- 26815178 TI - Predicting Marathon Time Using Exhaustive Graded Exercise Test in Marathon Runners. AB - The study aimed to investigate the correlation between time on a treadmill test and exhaustion 2 weeks before a road marathon and the subsequent road marathon performance time (MPT). The study recruited 59 runners entered in the Melbourne 2012 marathon, Canberra 2013 marathon, and Gold Coast 2013 marathon. Forty runners completed both the graded exercise treadmill test to exhaustion and the 42.2 km marathon. Nineteen participants dropped out of the study due to illness, injury, or did not begin the treadmill test. A statistically significant correlation was found between treadmill time and MPT (adjusted R(2) = 0.447). Sex, weekly running duration (t = -1.58, p = 0.12), years of running (t = 1.10, p = 0.28), and age (t = 0.94, p = 0.36) did not statistically correlate with MPT. The relationship between the graded exercise test and MPT can be used to predict MPT using y = -3.85x + 351.57, where y is MPT and x is treadmill time. This is a simple, accessible, and cost-effective method to aid athletes in predicting their race time over 42.2 km. Prediction of marathon time in a simple and accessible manner was believed to be useful to the growing population of marathon runners around the world. PMID- 26815179 TI - The Effects of Novel Ingestion of Sodium Bicarbonate on Repeated Sprint Ability. AB - This work examined the influence of an acute dose of sodium bicarbonate (NaHCO3) on buffering capacity and performance during a repeated sprint ability (RSA) protocol. Eleven (mean +/- SD: age 24.6 +/- 6.1 years; mass 74.9 +/- 5.7 kg; height 177.2 +/- 6.7 cm) participated in the study, undertaking 4 test sessions. On the first visit to the laboratory, each participant ingested 300 mg . kg(-1) of NaHCO3 (in 450 ml of flavored water) and blood samples were obtained at regular intervals to determine the individual times peak pH and HCO3. In subsequent visits, participants ingested 300 mg . kg(-1) of NaHCO3, 270 mg . kg( 1) body mass (BM) of NaCI, or no drink followed by a RSA cycling protocol (10 * 6 seconds sprints with 60 seconds recovery), which commenced at each individuals predetermined ingestion peak pH response time. Blood samples were obtained before exercise and after the first, fifth, and 10th sprint to determine the blood pH, HCO3, and lactate (La) responses. Total work completed during the repeated sprint protocol was higher (p <= 0.05) in the NaHCO3 condition (69.8 +/- 11.7 kJ) compared with both the control (59.6 +/- 12.2 kJ) and placebo (63.0 +/- 8.3 kJ) conditions. Peak power output was similar (p > 0.05) between the 3 conditions. Relative to the control and placebo conditions, NaHCO3 ingestion induced higher (p <= 0.05) blood pH and HCO3 concentrations before exercise and during the bouts, and higher lactate concentrations (p <= 0.05) after the final sprint. Results suggest that NaHCO3 improves the total amount of work completed during RSA through enhanced buffering capacity. PMID- 26815180 TI - [Serum relaxin in cervical incompetence patients]. AB - OBJECTIVE: To analyze the serum relaxin and clinical character of cervical incompetence patients and normal pregnant women. METHODS: A total of 33 cervical incompetence patients (research group) and 33 normal pregnancy women with the same gestational age (control group) were recruited into the study. The serum relaxin level was detected with enzyme labeled immunosorbent assay (ELSIA) in the two groups, and the cervical length of early pregnancy period (cm), body mass index (BMI, kg/m2), frequency of polycystic ovary syndrome (%), gestational diabetes mellitus/diabetes mellitus (%) and outcomes in the two groups were analyzed with independent samples t test and chi-square test. RESULTS: All the cervical incompetence patients were recruited between Feb. 2008 and Sept. 2012, with the average termination gestational age of 30+/-6 weeks. Among them, 15 (45.45%) was abortion, 12 (36.36%) was preterm birth, 6 (16.18%) was term birth. The average BMI before pregnancy was 27+/-4 kg/m2, and the average serum relaxin was 2,748+/-82 mg/L; for the 33 patients in the control group, the average termination gestational age was 38+/-3 weeks, and 1 (3.03%) of them was abortion, 4 (12.12%) was preterm birth, 28 (84.85%) was term birth. The average BMI before pregnancy was 23+/-3 kg/m2, the average serum relaxin was 2,602+/-126 mg/L. Compared with the control group, the research group had more patients who complicated with polycystic ovary syndrome and gestational diabetes mellitus/diabetes mellitus (P<0.01, <0.05) and worse pregnancy outcomes (P<0.01); the average BMI before pregnancy and the average serum relaxin level of the research group were significantly higher than control group (P<0.01, P<0.01). Analysis through the unconditional logistic regression showed that BMI and serum relaxin were both independent risk factors of cervical incompetence. CONCLUSIONS: The high level of serum relaxin is an independent risk factor of cervical incompetence; women with polycystic ovary syndrome may more likely to have cervical incompetence and serum relaxin may have the predictive value for cervical incompetence. PMID- 26815181 TI - [Analysis of 160 cases of C1 lateral mass screw fixation in patients with atlas occipitalization and occipito-cervical instability]. AB - OBJECTIVE: To summarize the clinical effect of C1 lateral mass screw fixation in patients with atlas occipitalization and occipito-cervical instability (OCI). METHODS: Patients of atlas occipitalization and OCI from June 2007 to October 2013 which had been treated by C1 lateral mass fixation in our institution were retrospective analyzed. The clinical neurologic function improvement rate and bone fusion rate were investigated at follow-ups. The nuances of the C1 lateral mass insertion were summarized. RESULTS: Among the 160 patients, 1 patient died, 1 got worse, 1 was stable, 155 got recovery and 2 lost to follow-up. Among the 157 cases within 12-52 months follow-up (mean 34 months), 147 cases got reduction and release from the cervico-medullary junction compression and 10 got no effective reduction which were resumed to anterior decompression at second surgery.At one year follow-up, 155 cases had solid bony fusion and 2 had no evident fusion.The entry point for C1 screw was located at the midpoint of the posterior surface of C1 facet and the screw was directed approximately between 0 40 degrees cephalad and approximately between 0-20 degrees medially. CONCLUSIONS: C1 lateral mass screw fixation is a safe and feasible method and could provide solid stability in patients with atlas occipitalization and OCI. The risk of placement of C1 screw could be decreased to a low rate after the preoperative evaluation and trajectory design. PMID- 26815182 TI - [Risk factors for osteoporotic fractures of spine in RA patients]. AB - OBJECTIVE: To investigate the risk factors of osteoporotic fractures (OPF) in patients with RA. METHODS: From February 2011 to March 2015, 244 patients with rheumatoid arthritis (RA) were treated in Department of Orthopedics, Huaibei People's Hospital, according to the occurrence of osteoporotic fractures (OPF) into the OPF group (n=31) and the non OPF group (n=213), observed two groups general information, glucocorticoid usinge, -28 joint disease activity score (DAS28), health status Questionnaire (HAQ), C-reactive protein (CRP), anti-cyclic citrullinated peptide (CCP) antibody, erythrocyte sedimentation rate (ESR), etc. RESULTS: OPF group the mean age and disease duration for (64.3+/-10.9) years and (9.0+/-3.3) years were significantly higher than that of non OPF group (57.4+/ 11.2) years and (6.0+/-2.7) years (P<0.05); OPF group and non OPF group ESR, CRP, anti CCP, HAQ and DAS28 difference was not statistically significant (P>0.05); OPF group sharp score (56.0+/-18.4), hormone use time (785 d), and hormone cumulant (7,100 mg.d) were significantly higher than that in non OPF group [sharp score (86.1+/-17.1), hormone use time (191 d), and hormone cumulant (1,900 mg.d)], the difference was statistically significant (P<0.05); OPF femoral neck, Ward area, total femur area and thoracic spine 2-3 bone mineral density T value significantly lower than non OPF group (P<0.05). CONCLUSION: Age and osteoporosis are risk factors for the occurrence of osteoporotic fractures in patients with rheumatoid arthritis, so patients should conduct a risk assessment to guide rational drug use. PMID- 26815183 TI - [Selection of indications and surgical treatment of basilar invagination with atlantoaxial dislocation]. AB - OBJECTIVE: To evaluate the indications and effect of surgical treatment of basilar invagination (BI) with atlantoaxial dislocation (AAD) on the basis of retrospective analysis of the clinical and imaging data of patients. METHODS: Consecutive 21 patients with BI and AAD were surgically treated in Department of Spinal Surgery, The First Affiliated Hospital of Xinjiang Medical University from July 2000 to December 2013. There were 10 males and 11 females, aged from 7 to 59 years, with a mean of 36.4 years. The clinical symptoms and signs was recorded, and preoperative imaging examination including anteroposterior, lateral, dynamic films, MRI, CT and 3-dimensional reconstruction views of cervical spine were performed to identify the series. All cases were treated with operation. Neurological function was assessed by JOA scale and NDI score before, after surgery and at final follow-up. The postoperative X-rays, MRI or CT was taken to observed the results of decompression, fixation and fusion. RESULTS: There were 5 cases operated by posterior approach, combined anterior and posterior approach in 16 cases, atlantoaxial fixation in 2 cases, occipitocervical fixation in 19 cases. The average operation time was 200 mins, blood loss was 230 ml. Except for 2 death cases, 19 cases were followed up, the followed-up was arranged from 13 to 42 months, with an average of 21.6 months. Compared with preoperative parameters (7.8+/-1.3), the postoperative scores of JOA decreased significantly (14.1+/-0.5) and at the final follow-up (16.2+/-0.7) (P<0.05); compared with preoperative parameters (65.7+/-11.2), the postoperative scores of NDI decreased significantly (28.2+/-9.6) and at the final follow-up (22.7+/-7.4) (P<0.05) and no significant difference in JOA or NDI score existed between post-operation and last follow-up (P>0.05). The perioperative complications was discovered in 6 cases, including infection in 2 cases, cerebrospinal fluid (CSF) leakage in 2 cases, respiratory dysfunction, cleft palate in 1 case, respectively. CONCLUSION: BI with AAD can be treated by anterior, posterior or combined approaches. Careful evaluation, proper selection of indications and prevention of perioperative complications are important consideration to ensure the success of surgery. PMID- 26815184 TI - [Effect of 10-hydroxycamptotbecine on the expression of VEGF in rheumatoid arthritis synovial fibroblasts]. AB - OBJECTIVE: To study the effect of 10-Hydroxycamptotbecine (10-HCPT) on the expression of vascular endothelial growth factor (VEGF) in rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: RASFs were isolated form synovial tissue of RA patients and cultured in vitro. 10-HCPT (3.0*10(-6) mol/L, 3.0*10(-5) mol/L) and Methotrexate (MTX) (2.0*10(-6) mol/L, 2.0*10(-5) mol/L) with different concentrations were used to treat RASFs for 48 hours, and RASFs without 10-HCPT and MTX treatment were served as the control group. The level of VEGF in the supernatant of RASFs culture was measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with control group, high and low dose 10-HCPT groups showed significant values on the effect of inhibiting the expression of VEGF in RASFs. Compared with low-dose MTX group, both high and low dose 10-HCPT groups showed significant difference (P<0.05); compared with high-dose MTX group, the high-dose 10-HCPT group had significant difference (P<0.05). CONCLUSION: Compared with MTX, 10-HCPT showed significant effect on inhibiting the expression of VEGF in RASFs. PMID- 26815185 TI - [Chromosome examination of missed abortion patients]. AB - OBJECTIVE: To investigate the relationship between the missed abortion and chromosome abnormality and guide the healthy birth. METHODS: From June 2014 to April 2015 in Tianjin central hospital of gynecology and obstetrics, we examined venous blood from 90 missed abortion couples for chromosome karyotype by lymphocyte culture method and we also examined their chromosome karyotype of abortion villus samples by high-throughput sequencing technologies. RESULTS: Out of the 90 couples' blood chromosome examinations, 7 were abnormal, and the abnormal rate was 3.89%, including 3 cases reciprocal translocation, 2 cases robertsonian translocation and 2 cases inversion. Abortion villus samples from the same population were also checked, of which 85 cases succeeded, with the success rate of 94.4%. Among them, villi chromosome abnormalities were found in 50 cases, including 39 cases with abnormal chromosome numbers, 11 cases with abnormal chromosome structure, and the total abnormal rate was 58.8%. In addition, the villi chromosome abnormality rate of patients with recurrent missed abortion (>=2 times) and first missed abortion were 61.7% and 55.2%, respectively, and the difference was not significant (P>0.05). The villi chromosome abnormality rate of pregnant women with age>=35 years old was 71.1%, while the pregnant women with aged <35 years old was 45% (P<0.05). CONCLUSIONS: Chromosome abnormality is an important cause of missed abortion; villi chromosome abnormality rate has nothing to do with the number of missed abortion; pregnant woman with age>=35 years old is risk factor of the villi chromosome abnormality. PMID- 26815186 TI - [Associated risk factors of ischemic events for spontaneous cervical artery dissection]. AB - OBJECTIVE: This study sought to identify risk factors of ischemic events and predictors of outcome for spontaneous cervical artery dissection (sCAD). METHODS: One hundred and sixty one patients diagnosed as sCAD were classified as patients with (n=77) and without (n=84) cerebral ischemia. Demographics, vascular risk factors and imaging features were compared between the two groups. Multivariate Cox regression analysis was performed to identify predictors of primary end-point events (all cause stroke and death) at follow-up. RESULTS: Patients with cerebral ischemia had a higher prevelence of hypertension and diabetes mellitus (62.3% vs 41.7%, 14.3% vs 6.2%, P<0.05). Patients with cerebral ischemia were more likely to present with stenosis (61.0% vs 23.8%, P<0.001) and less likely to present with aneurysmal dilatation (19.5% vs 44.0%, P<0.001) and double lumen (22.1% vs 38.1%, P<0.05). There was significant positive association of diabetes mellitus (odds ratio 3.095; 95% confidence interval, 1.273 to 7.524, P=0.013) and stenosis (odds ratio 4.335, 95% confidence interval, 2.123 to 8.854, P<0.001), and an inverse association of aneurysmal dilatation (odds ratio 0.429, 95% confidence interval, 0.198 to 0.930, P=0.032) with occurrence of ischemic events in patients with sCAD. At a mean follow-up of 16.0 months, overall incidence of primary end point was 9.3% (n=15). Cox regression analysis showed cerebral ischemia at onset, arterial occlusion, obesity or overweightness were significant predictors of the primary endpoint. CONCLUSIONS: This study confirms that diabetes mellitus and arterial stenosis are risk factors of ischemic events for sCAD patients. Cerebral ischemia at onset, arterial occlusion, obesity or overweightness are predictors of primary endpoint at follow-up. PMID- 26815187 TI - [Carpal tunnel syndrome with cervical spondylotic radiculopathy: a clinical and electrophysiological study]. AB - OBJECTIVE: To study the clinical and electrophysiological characteristics of carpal tunnel syndrome (CTS) with cervical spondylotic radiculopathy (CSR) and simple-CTS, and compare the effect of double crush with that of simple entrapment on a nerve and investigate the association between CTS and CSR. METHOD: From January 2011 to August 2014, clinical data from 96 patients with double crush syndrome (DCS, CTS with CSR) and 165 patients with simple-CTS were examined, and the electrophysiologic parameters of median nerve in patients with DCS were compared with that in patients with simple-CTS. RESULTS: In 96 patients with DCS, most of them were female; neck and shoulder pain or simultaneously accompanied by numbness and pain of upper limb was observed in 34 patients, upper limb symptoms and hand weakness and muscle atrophy were observed in the other 62 patients, 124 median nerves with abnormal conduction were found in these DCS patients, including 68 cases with unilateral abnormalities and 28 cases with bilateral abnormalities. Cervical radiculopathies of the C5-7 mainly involved in patients with DCS.223 median nerves with abnormal conduction found in the 165 patients with simple-CTS, including 107 cases with unilateral abnormalities and 58 cases with bilateral abnormalities. The average sensory nerve conduction velocity (SCV), motor nerve conduction velocity (MCV) and distal motor latency (DML) of median nerve for DCS and simple-CTS were (32+/-7) m/s vs (35+/-5) m/s, (55+/-7) m/s vs (57+/-5) m/s and (4.6+/-1.6) ms vs (4.0+/-0.8) ms, respectively, and their corresponding amplitudes were 6.4 uV vs 9.5 uV, 10.9 mV vs 13.1 mV and 11.3 mV vs 14.1 mV, respectively. The SCV, MCV and DML and their corresponding amplitude of DCS were significantly greater decreased than that of simple-CTS (P<0.01). CONCLUSION: DCS is a common clinical syndrome, and patients with DCS may have neck and shoulder symptoms in addition to the common manifestations of simple CTS. Abnormal conduction of median nerve of CTS with CSR is more severe than that of simple-CTS, which neurophysiologically proves the association between CTS and CSR and supports double crush hypothesis. PMID- 26815188 TI - [Early diagnosis of diabetic autonomic neuropathy by corneal confocal microscopy]. AB - OBJECTIVE: To investigate the early diagnostic value of corneal confocal microscopy by observing corneal innervation alteration in patients with autonomic neuropathy with impaired glucose tolerance. METHODS: A total of 50 subjects with neuropathy with impaired glucose tolerance or newly diagnosed type 2 diabetes, including 20 subjects with diabetic autonomic neuropathy (AN) and 30 subjects with non-autonomic neuropathy (NAN) according to the result of cardiovascular autonomic function test, and 50 aged-matched control subjects were included in this study. All the subjects came from the Department of Neurology and Endocrine from Jan to Aug 2014, and underwent a detailed evaluation of neuropathic symptoms, corneal confocal microscopy, the Survey of Autonomic Symptoms, sympathetic skin response and contact heat evoked potential test. RESULTS: T test indicated patients with AN had significant reductions in nerve branch density (NBD) and nerve fiber density (NFD), and increase in corneal nerve fiber tortuosity (NFT) compared with the NAN patients (t=10.17, 4.81, 7.78; P=0.002, 0.031, 0.003). Though corneal nerve fiber length (NFL) decreased ((15+/-5) vs (13+/-5) mm/mm2), there is no statistic significance (t=1.275, P=0.232). Pearson's correlation analysis showed the severity of autonomic neuropathy significantly correlated with cornea nerves damage. The Survey of Autonomic Symptoms (SAS) significantly correlated with NFT, NFD, NFL (r=0.628, -0.304, 0.217; P<0.001, P=0.002, 0.03). NFT was the most significant determinant for the severity of autonomic neuropathy among the four observed parameters. CONCLUSION: Corneal confocal microscopy provides a new sensitive non-invasive means to detect autonomic nerve fiber damage in patients with impaired glucose tolerance and would be of value in assessing neuropathic autonomic symptoms in clinical practice and epidemiologic studies. PMID- 26815189 TI - [Anti-N-methyl-D-aspartate receptor encephalitis:clinical analysis of 11 cases]. AB - OBJECTIVE: To analyze the clinical manifestation, laboratory findings, radiological data of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis. METHODS: The clinical manifestation, laboratory findings, radiological data of eleven patients with anti-NMDA receptor encephalitis were analyzed. RESULTS: Main symptoms included epilepsy presented in 9 cases, psychiatric symptom in 7 cases, dyskinesia in 5 cases, autonomic dysfunction in 3 cases. The anti-NMDA receptor antibody was found in all the patients' cerebrospinal fluid (CSF). No teratoma was detected in any of the patients, and 1 case had lung cancer. All the patients received immune therapy. And at discharge, 4 cases recuperated generally, 7 cases had different degrees of dysfunction. After telephone follow-up of 1-18 months, 1 case was lost, 3 cases had complete recovery, and 7 cases had different degrees of sequela. CONCLUSION: When Patients without mental illness history presents with unexplained mental symptoms accompanied by seizures, memory impairment, disturbance of consciousness, movement disorders, autonomic dysfunction and other symptoms, anti-NMDA receptor antibodies studies in both serum and CSF should be done as early as possible in order to facilitate early diagnosis, early treatment and improve the prognosis. PMID- 26815190 TI - [Assessment of congenital vascular rings with MDCT on children]. AB - OBJECTIVE: To evaluate the value of MDCT on diagnosis of congenital vascular rings on children. METHODS: Retrospective analysis on 43 cases of congenital vascular rings, which underwent MDCT during Oct 2008 to Dec 2014 in Beijing Anzhen hospital affiliated to capital medical university. 21 males, 22 females; age from 29 days to 8 years, mean age 1.46 years, 33 cases are not beyond 1 year. All the results were compared with that of the echocardiogram or record of the surgery. The CT data were read and reconstructed with multiplanar reconstruction (MPR), maximum intensity projection (MPR), minimum intensity projection (MinIP), volume rendering (VR). The image quality was evaluated and the diagnostic value and the standard diagnostic program were discussed. RESULTS: Of 43 cases of vascular rings:there were 6 cases of pulmonary artery sling (13.95%), 9 cases of right aortic arch /aberrant left subclavian artery(20.93%), 18 cases of left aortic arch/aberrant right subclavian artery (41.86%), 10 cases of double aortic arch (23.26%). Forty cases (93.02%) were combined with other cardiovascular or pulmonary malformations. Every malformation was revealed clearly and proved by echocardiogram. Of 3 cases (6.98%) without any other malformation, 2 cases were combined tracheal stenosis. A pulmonary artery sling was proved by surgery; the other 2 cases were double aortic arch. All the images of 43 cases could be reconstructed well. MPR and VR showed the origin, shape, and whole course of vascular rings directly; MinIP and VR could display the shape, width and development of trachea, revealed the relationship between vascular rings, trachea and esophagus. It was important to show and measure the component vascular of the ring. Attention should be paid to the whole course of trachea and esophagus, especially those segments which were close to the ring vascular. The tracheal stenosis as well as intra-cardio anatomy malformations should be measured on MPR images if existed. According to the segmental analysis method, comes the overall final diagnosis. A standard diagnostic program on vascular ring was proposed. CONCLUSION: MDCT axis images with various 3D post processing methods could reveal the compose of vascular rings and the relationship between vascular rings, trachea and esophagus. PMID- 26815191 TI - [Observation of curative effect in treatment of distal tibial fractures with minimall invasive percutaneous technique]. AB - OBJECTIVE: To explore the application of minimally invasive percutaneous plate osteosynthesis (MIPPO) the clinical curative effect of treatment of fractures of the distal tibia. METHODS: From 2010 June to 2014 June, the application of MIPPO technology combined with LCP (low bend medial distal tibial plates) for treatment of 67 cases of distal tibial fracture patients, to evaluate the healing of fracture, function etc. RESULTS: 67 patients with effective follow-up, time was 6 20 months, mean 15 months. The incision healed in one stage, 3 weeks. The effect of 12-16 weeks to fracture healing standard weight, nomalunion and nonunion cases, no fracture, bone plate and screw loosening, exit and other phenomena. The postoperative function was evaluated according to Johner-Wruch criteria, excellent in 45 cases, good in 16 cases, 6 cases, poor in 0 cases. CONCLUSION: MIPPO technique combined with LCP (low bend medial distal tibial plates) in treatment of distal tibial fractures in accord with biological osteosynthesis requirements, is a recommendable method to treat fracture extension. PMID- 26815193 TI - [Analyze the factors influencing multi-electrode synchronous radiofrequency ablation via switching controller in ex vivo bovine liver]. AB - OBJECTIVE: To investigate the effects of different electrode exposed end and different ablated time on lesion size of Cool-tip multi-electrode synchronous radiofrequency ablation via switching controller in ex vivo bovine liver. METHOD: Twelve combinations of different electrode exposed end (2 cm, 3 cm and 4 cm) were used, and different ablated time (12, 16, 20 and 24 mins) was as experimental parameter. Ablated lesions in longitudinal diameter, transverse diameter and volume were measured. Analyze the factors influencing the lesion size with ANOVA or t test. RESULTS: The ablated lesions with 3 cm exposed end electrodes were more stable and the spheroidal rate is more close to 1. When ablated 24 mins with 4 cm exposed end electrodes, the longitudinal diameter, transverse diameter and volume were (7.66+/-0.21), (6.50+/-0.34) cm and (172+/-12) cm3, respectively. When the ablated time was constant, the lesions increased with the exposed end length of the electrodes increased. All the data among groups was statistically significant (P<0.01) unless the transverse diameters between 3 and 4 cm exposed end electrode. When the exposed end length of electrodes was constant, the lesions increased with the ablated time increased as a whole. But there was no significant difference in most of the adjacent groups. Only the longitudinal diameters and volumes of 4 cm exposed end electrodes between 20 and 24 min were statistically significant (P<0.05). CONCLUSION: Within the experimental range, the lesion size ablated by Cool-tip multi-electrode synchronous radiofrequency ablation via switching controller increased with the electrode exposed end and ablated time increased. The spheroidal rate of the ablated lesions with 3 cm exposed end is more close to 1. PMID- 26815192 TI - [Clinical characteristics of multiple primary cancer associated with esophageal squamous carcinoma]. AB - OBJECTIVE: To examine the characteristics of esophageal squamous cancers with multiple primary cancers in another organ. METHODS: Between January 2012 and December 2014, 3 104 patients with esophageal squamous cell carcinoma treated in Cancer Institute and Hospital, Chinese Academy of Medical Sciences, were reviewed for the presence of an additional primary cancer retrospectively. The patients were divided into two groups according to whether they had multiple primary cancer. RESULTS: Totally 369 (11.9%) patients were found multiple primary cancer in the other organs. Among these patients, 72.4% was found synchronously, another primary cancer was found in the head and neck region in 211 (6.8%), in the stomach in 140 (4.2%), and in the lung, colon, breast, and other locations in the remaining patients. Of the 211 patients with another primary cancer in the head and neck region, 156 (73.2%) had hypopharyngeal cancer. Furthermore, the incidence of intraesophageal multiple cancerous lesion in the patients with primary cancer in the head and neck region was significantly higher than that in those whose other primary cancers were gastric cancer or in those with non multiple primary cancer (P<0.01). CONCLUSION: There is a high incidence of multiple primary cancers in patients with esophageal squamous carcinoma, mostly found synchronously. The leading multiple primary cancers were head and neck cancer and stomach cancer. Intraesophageal multiple cancerous lesion is an indicator for a second primary cancer in head and neck. A better knowledge of the relationships between esophageal carcinoma and cancers in other organs may lead to earlier detection of other primary cancers and improved therapeutic results. PMID- 26815194 TI - [p14ARF enhances cisplatin-induced apoptosis in human osteosarcoma cells in p53 independent pathway]. AB - OBJECTIVE: To study effect of tumor suppressor p14ARF on cisplatin-induced apoptosis in human osteosarcoma cells with its molecular mechanisms to provide evidences for increasing chemosensitivity of osteosarcoma. METHODS: pcDNA3.1 p14ARF plasmid was stable transfected into MG63 cells lack of p14ARF expression. Expression of p14ARF on mRNA and protein level was evaluated with RT-PCR and Western blot. MG63, MG63-vec and MG63-ARF cells were treated with cisplatin. Cell growth inhibition and IC50 were determined through MTT assay. Apoptosis was detected using fluorescence-activated cell sorting and Hoechst33258 staining. The expression of p53, Bax, p21, Mdm2, Fas, Caspase-3, caspase-9 and PARP was detected with Western blot. RNAi was used to silence p53. Cells were pre-treated with Caspase-9 specific inhibitor Z-LEHD-FMK to determine whether the effect was Caspase-9-dependent. RESULTS: There was no expression of p14ARF in MG63 and MG63 vec cells but obvious expression in MG63-ARF cells on mRNA and protein level. Cell viability was 84.2%+/-4.3%, 80.8%+/-4.3% and 58.9%+/-5.4% in MG63, MG63-vec, and MG63-ARF cells after treatment of cisplatin for 72 h. IC50 was (11.1+/-0.6), (10.7+/-0.9) and (7.2+/-0.7) umol/L. The apoptotic rate was 13.6%, 18.5% and 35.9% in groups, There were more obvious apoptotic more changes in MG63-ARF cells than MG63 and MG63-vec cells, and activation of Caspase-3, 9 and PARP on higher level in U2OS-ARF cells after stimulation with cisplatin for 72 h. The expression of p53, Bax, p21, Mdm2 and Fas, in MG63-vec and MG63-ARF cells did not changed (P>0.05). The expression of p53 was effectively and continuously suppressed by p53-siRNA in U2OS-vec and U2OS-ARF cells. The p53 silencing did not alter the cytotoxicity mediated by cisplatin treatment for 72 h (P>0.05). Cell viability was 96.8%+/-3.6%, 54.1%+/-5.7% and 89.5%+/-5.1% in Z-LEHD-FMK, cisplatin and Z LEHD-FMK+cisplatin groups. CONCLUSION: p14ARF enhances cisplatin-induced apoptosis in human osteosarcoma MG63 cells in p53-independent caspase-9-dependent pathway, in which the intrinsic mitochondrial apoptotic pathway is involved. PMID- 26815195 TI - Identification of a Benzoisoxazoloazepine Inhibitor (CPI-0610) of the Bromodomain and Extra-Terminal (BET) Family as a Candidate for Human Clinical Trials. AB - In recent years, inhibition of the interaction between the bromodomain and extra terminal domain (BET) family of chromatin adaptors and acetyl-lysine residues on chromatin has emerged as a promising approach to regulate the expression of important disease-relevant genes, including MYC, BCL-2, and NF-kappaB. Here we describe the identification and characterization of a potent and selective benzoisoxazoloazepine BET bromodomain inhibitor that attenuates BET-dependent gene expression in vivo, demonstrates antitumor efficacy in an MV-4-11 mouse xenograft model, and is currently undergoing human clinical trials for hematological malignancies (CPI-0610). PMID- 26815197 TI - Multifunctional lanthanide-organic frameworks for fluorescent sensing, gas separation and catalysis. AB - Two lanthanide MOFs based on 3,3'-((2,3,6,7-tetramethoxyanthracene-9,10 diyl)bis(4,1-phenylene))diacrylic acid (H2LOMe), [Eu(LOMe)1.5(H2O)2].3.5DMA.2H2O (1) and [Pr(LOMe)(H2O)4].2.5DMA.3H2O (2) were synthesized under solvothermal conditions. Complex 1 displayed a 2D net with single nodal 44-sql topology, which further formed a 3D supramolecular architecture by strong pi?pi interaction. Complex 2 featured a 3D open framework with {42.84}-PtS topology. The PL spectrum results showed that 2 has potential application not only in the sensing of small organic molecules, such as DMF and NB, but also in detecting Al3+ and nitroaromatic derivatives. Furthermore, 2 also showed the selective adsorption of CO2 over CH4 and high catalytic activities with the cyanosilylation reaction. PMID- 26815196 TI - Changes in CYP2C19 enzyme activity evaluated by the [(13)C]-pantoprazole breath test after co-administration of clopidogrel and proton pump inhibitors following percutaneous coronary intervention and correlation to platelet reactivity. AB - Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is used for the prevention of cardiovascular events following percutaneous coronary intervention (PCI). These agents increase the risk of gastrointestinal bleeding. To prevent these events, proton pump inhibitors (PPI) are routinely prescribed. It has been reported that with the exception of pantoprazole and dexlanzoprazole, PPIs can impede conversion of clopidogrel by cytochrome P450 2C19 (CYP2C19) to its active metabolite, a critical step required for clopidogrel efficacy. Changes in CYP2C19 enzyme activity (phenotype) and its correlation with platelet reactivity following PPI therapy has not yet been fully described. In this study we attempted to determine if the [ (13)C]-pantoprazole breath test (Ptz-BT) can evaluate changes in CYP2C19 enzyme activity (phenoconversion) following the administration of PPI in coronary artery disease (CAD) patients treated with DAPT after PCI. Thirty (30) days after successful PCI with stent placement, 59 patients enrolled in the Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects (SPICE) trial (ClinicalTrials.gov Identifier: NCT00930670) were recruited to participate in this sub study. Patients were randomized to one of 4 antacid therapies (omeprazole, esomeprazole. pantoprazole or ranitidine). Subjects were administered the Ptz-BT and platelet function was evaluated by vasodilator-stimulated phosphoprotein (VASP) phosphorylation and light transmittance aggregometry before and 30 d after treatment with antacid therapy. Patients randomized to esomeprazole and omeprazole had greater high on-treatment platelet reactivity and lowering of CYP2C19 enzyme activity at Day 60 after 30 d of PPI therapy. Patients randomized to ranitidine and pantoprazole did not show any changes in platelet activity or CYP 2C19 enzyme activity. In patients treated with esomeprazole and omeprazole, changes in CYP2C19 enzyme activity (phenoconversion) correlated well with changes in platelet reactivity. Co-administration of omeprazole or esomeprazole in patients treated with clopidogrel results in lower CYP2C19 enzyme activity and increased platelet reactivity as measured by VASP phosphorylation test while patients given pantoprazole or ranitidine did not show any significant changes in CYP2C19 enzyme activity and platelet reactivity. PMID- 26815198 TI - Long-term evolution and predictive factors of mild inflammatory bowel disease. AB - BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are potentially progressive diseases. Few data are available on the prevalence and the factors associated with mild inflammatory bowel diseases (IBD). AIM: Our aim was to assess the natural history of mild CD and mild UC and to identify predictive factors of mild evolution over the long term. METHODS: Retrospective study of IBD patients registered in the database of the university hospital CHU of Liege, Belgium. Mild CD was defined as an inflammatory luminal disease (no stricture, abdominal or perianal fistulae) requiring no immunomodulator (IM), anti-TNF and no surgery. Mild UC was defined as no requirement for IM, anti-TNF and no colectomy. RESULTS: Four hundred and seventy-three CD and 189 UC were included (median follow-up: 13 and 11 years respectively). At 1 year, 147 patients had mild CD. At 5 years and the maximum follow-up, 56% and 13% patients still had mild CD, respectively. At 1 year, 142 patients had mild UC. At 5 years and the maximum follow-up, 72% and 44% still had a mild UC, respectively. Factors associated with long-term mild CD and UC were older age at diagnosis and absence of corticosteroids in the first year. In UC proctitis location was associated with mild UC. CONCLUSIONS: In this cohort, 90% of CD patients and 3/4 of UC with mild disease at 1 year lost their mild disease status over time. An old age at diagnosis was predictive of the persistence of a mild CD and UC. PMID- 26815200 TI - DNMT1 and HDAC2 Cooperate to Facilitate Aberrant Promoter Methylation in Inorganic Phosphate-Induced Endothelial-Mesenchymal Transition. AB - While phosphorus in the form of inorganic or organic phosphate is critically involved in most cellular functions, high plasma levels of inorganic phosphate levels have emerged as independent risk factor for cardiac fibrosis, cardiovascular morbidity and decreased life-expectancy. While the link of high phosphate and cardiovascular disease is commonly explained by direct cellular effects of phospho-regulatory hormones, we here explored the possibility of inorganic phosphate directly eliciting biological responses in cells. We demonstrate that human coronary endothelial cells (HCAEC) undergo an endothelial mesenchymal transition (EndMT) when exposed to high phosphate. We further demonstrate that such EndMT is initiated by recruitment of aberrantly phosphorylated DNMT1 to the RASAL1 CpG island promoter by HDAC2, causing aberrant promoter methylation and transcriptional suppression, ultimately leading to increased Ras-GTP activity and activation of common EndMT regulators Twist and Snail. Our studies provide a novel aspect for known adverse effects of high phosphate levels, as eukaryotic cells are commonly believed to have lost phosphate-sensing mechanisms of prokaryotes during evolution, rendering them insensitive to extracellular inorganic orthophosphate. In addition, our studies provide novel insights into the mechanisms underlying specific targeting of select genes in context of fibrogenesis. PMID- 26815199 TI - Barriers and Facilitators to the Uptake and Maintenance of Healthy Behaviours by People at Mid-Life: A Rapid Systematic Review. AB - BACKGROUND: With an ageing population, there is an increasing societal impact of ill health in later life. People who adopt healthy behaviours are more likely to age successfully. To engage people in health promotion initiatives in mid-life, a good understanding is needed of why people do not undertake healthy behaviours or engage in unhealthy ones. METHODS: Searches were conducted to identify systematic reviews and qualitative or longitudinal cohort studies that reported mid-life barriers and facilitators to healthy behaviours. Mid-life ranged from 40 to 64 years, but younger adults in disadvantaged or minority groups were also eligible to reflect potential earlier disease onset. Two reviewers independently conducted reference screening and study inclusion. Included studies were assessed for quality. Barriers and facilitators were identified and synthesised into broader themes to allow comparisons across behavioural risks. FINDINGS: From 16,426 titles reviewed, 28 qualitative studies, 11 longitudinal cohort studies and 46 systematic reviews were included. Evidence was found relating to uptake and maintenance of physical activity, diet and eating behaviours, smoking, alcohol, eye care, and other health promoting behaviours and grouped into six themes: health and quality of life, sociocultural factors, the physical environment, access, psychological factors, evidence relating to health inequalities. Most of the available evidence was from developed countries. Barriers that recur across different health behaviours include lack of time (due to family, household and occupational responsibilities), access issues (to transport, facilities and resources), financial costs, entrenched attitudes and behaviours, restrictions in the physical environment, low socioeconomic status, lack of knowledge. Facilitators include a focus on enjoyment, health benefits including healthy ageing, social support, clear messages, and integration of behaviours into lifestyle. Specific issues relating to population and culture were identified relating to health inequalities. CONCLUSIONS: The barriers and facilitators identified can inform the design of tailored interventions for people in mid life. PMID- 26815202 TI - Detection of Tephra Layers in Antarctic Sediment Cores with Hyperspectral Imaging. AB - Tephrochronology uses recognizable volcanic ash layers (from airborne pyroclastic deposits, or tephras) in geological strata to set unique time references for paleoenvironmental events across wide geographic areas. This involves the detection of tephra layers which sometimes are not evident to the naked eye, including the so-called cryptotephras. Tests that are expensive, time-consuming, and/or destructive are often required. Destructive testing for tephra layers of cores from difficult regions, such as Antarctica, which are useful sources of other kinds of information beyond tephras, is always undesirable. Here we propose hyperspectral imaging of cores, Self-Organizing Map (SOM) clustering of the preprocessed spectral signatures, and spatial analysis of the classified images as a convenient, fast, non-destructive method for tephra detection. We test the method in five sediment cores from three Antarctic lakes, and show its potential for detection of tephras and cryptotephras. PMID- 26815201 TI - Activation of KCNQ channels located on the skeletal muscle membrane by retigabine and its influence on the maximal muscle force in rat muscle strips. AB - Retigabine is a new antiepileptic drug with the main mechanism of action: activation of voltage-gated potassium channels (Kv7) represented in many tissues including the excitable cells-neuronal and muscular. The aim of this article is to determine the role of potassium channels located on the skeletal muscle membrane in the in vivo and in vitro reduction of muscle contractile activity induced by retigabine. We studied the effects of retigabine on the motor function in vivo using a bar holding test and exploratory activity using open field test in rats. Electrical field stimulation (EFS) was applied to skeletal muscle strips in vitro in order to evaluate muscular activity. We registered a significant decrease in the muscle tone and exploratory activity of rats, treated orally with 60 mg/kg bw retigabine. In vitro experiments showed decrease in the maximal muscle force of strips in the presence of retigabine in the medium after both indirect (nerve-like) and direct (muscle-like) stimulation. The effects were fully antagonized by XE-991 (Kv7 channel blocker), which supports our hypothesis about the relation between these types of potassium channels and the observed change in the muscle force. Based on these results, we can conclude that skeletal muscle Kv7 channels play a significant role in the myorelaxation and reduced muscle force registered after treatment with Kv7 channels openers (e.g., retigabine). The hyperpolarization of skeletal muscle membrane caused by accelerated K(+) efflux may be the underlying cause for the effect of retigabine on the muscle tone. PMID- 26815204 TI - Long-Range Magnetic Ordering and Switching of Magnetic State by Electric Field in Porous Phosphorene. AB - We explored the possibility of long-range magnetic ordering in two-dimensional porous phosphorene (PP) layer by means of ab-initio calculations. The self passivated pore geometry showed a nonmagnetic state while the pore geometry with dangling bond at two zigzag edges with a distance of 7.7 A preferred an antiferromagnetic ordering (AFM). Pore to pore magnetic interaction with a distance of 13.5 A between two pores was found to be remarkably long ranged, and this emerges from the interactions between the magnetic tails of the edge states in the armchair direction. The AFM state was persisted by the oxidation of the edge. Interestingly, the long-range AFM ordering changed to long-range ferromagnetic (FM) ordering by external electric field. The results are noteworthy in the interplay between electric field and electronic spin degree of freedom in phosphorene studies and may also open a promising way to explore phosphorene-based spintronics devices. PMID- 26815203 TI - Effects of feeding state on anticoagulation in adult goats treated with warfarin. AB - For the continued development of improved mechanical circulatory systems, longer term evaluation of new devices in animal model experiments may be critical. The effects of anticoagulants in adult goats have not been well studied. We assessed the effects of oral warfarin in three adult goats during fasting or after feeding. The goats [weighing 57.8 +/- 8.1 kg (53.0-67.2 kg)] were administered warfarin orally beginning at a dose of 5 mg/day and then increasing to 10, 20, 40, and 60 mg every 2 weeks. One goat (receiving 10 mg/day warfarin) was killed on day 27 because of the inability to stand. After administration of 60 mg warfarin, the remaining goat received no warfarin for 4 days to return to coagulated state. The goats were then fasted and treated with 40 mg warfarin. During warfarin administration, both goats required a dose of 60 mg/day to achieve International Normalized Ratios (INRs) of approximately 2.5; however, when, the animals were in the fasted condition, precipitous extension of INR was observed in 5 days. After resuming feeding, the INR was reduced to the proper range. We showed the tendency that warfarin therapy in goats required higher doses than the doses administered to human patients and that the effects of therapy were related to the feeding state. The results of this study provide important information for development of anticoagulation protocols to assess mechanical circulatory support devices for long-term use in preclinical examination. PMID- 26815205 TI - High-Sensitivity Measurement of Density by Magnetic Levitation. AB - This paper presents methods that use Magnetic Levitation (MagLev) to measure very small differences in density of solid diamagnetic objects suspended in a paramagnetic medium. Previous work in this field has shown that, while it is a convenient method, standard MagLev (i.e., where the direction of magnetization and gravitational force are parallel) cannot resolve differences in density <10( 4) g/cm(3) for macroscopic objects (>mm) because (i) objects close in density prevent each other from reaching an equilibrium height due to hard contact and excluded volume, and (ii) using weaker magnets or reducing the magnetic susceptibility of the medium destabilizes the magnetic trap. The present work investigates the use of weak magnetic gradients parallel to the faces of the magnets as a means of increasing the sensitivity of MagLev without destabilization. Configuring the MagLev device in a rotated state (i.e., where the direction of magnetization and gravitational force are perpendicular) relative to the standard configuration enables simple measurements along the axes with the highest sensitivity to changes in density. Manipulating the distance of separation between the magnets or the lengths of the magnets (along the axis of measurement) enables the sensitivity to be tuned. These modifications enable an improvement in the resolution up to 100-fold over the standard configuration, and measurements with resolution down to 10(-6) g/cm(3). Three examples of characterizing the small differences in density among samples of materials having ostensibly indistinguishable densities-Nylon spheres, PMMA spheres, and drug spheres-demonstrate the applicability of rotated Maglev to measuring the density of small (0.1-1 mm) objects with high sensitivity. This capability will be useful in materials science, separations, and quality control of manufactured objects. PMID- 26815207 TI - Focus on: Diagnostic and prognosis of severely traumatized patients. PMID- 26815206 TI - Drug levels, immunogenicity and assessment of active sacroiliitis in patients with axial spondyloarthritis under biologic tapering strategy. AB - The aim of the study was to assess drug levels, immunogenicity and sacroiliitis on MRI in patients with axial spondyloarthritis under biologic tapering strategy. Consecutive patients with axial spondyloarthritis who remained in low disease activity more than 1 year after dose tapering of infliximab and adalimumab were included. Plasma drug concentrations of TNF inhibitors and anti-drug antibodies were determined, and MRI of sacroiliac joints was evaluated. Of twenty patients included, eighteen had therapeutic drug levels, no patient had anti-drug antibodies, and no patient had active sacroiliitis on MRI. These data could support the biologic tapering strategy and their maintenance over time. PMID- 26815208 TI - Base excess determined within one hour of admission predicts mortality in patients with severe pelvic fractures and severe hemorrhagic shock. AB - BACKGROUND: Unstable pelvic ring fractures with exsanguinating hemorrhages are rare but potentially lifethreatening injuries. The aim of this retrospective study was to evaluate whether early changes in acid- base parameters predict mortality of patients with severe pelvic trauma and hemorrhagic shock. METHODS: Data for 50 patients with pelvic ring disruption and severe hemorrhage were analyzed retrospectively. In all patients, the pelvic ring was temporarily stabilized by C-clamp. Patients with ongoing bleeding underwent laparotomy with extra and/or intraperitoneal pelvic packing, as required. Base excess, lactate, and pH were measured upon admission and at 1, 2, 3, 4, 6, 8, and 12 h postadmission. Patients were categorized as early survivors (surviving the first 12 h after admission) and nonsurvivors. Statistical analysis was performed by Mann-Whitney test; significance was assumed at p < 0.05. Receiver operating characteristic curves were generated for early mortality from each acid-base variable. RESULTS: Sixteen patients (32%) were nonsurvivors due to hemorrhagic shock (n = 13) or severe traumatic brain injury (n = 3). Thirty-four patients were early survivors. Base excess, lactate, and pH significantly discriminated between early survivors and nonsurvivors. Base excess determined 1 h after admission discriminated most strongly, with an area under the receiver operating characteristic curve of 0.915 (95% confidence interval, 0.836-0.993; p < 0.001). CONCLUSION: Base excess, lactate, and pH discriminate early survivors from nonsurvivors suffering from severe pelvic trauma and hemorrhagic shock. Base excess measured 1 h after admission best predicted early mortality following pelvic trauma with concomitant hemorrhage. PMID- 26815209 TI - Development and validation of the revised injury severity classification score for severely injured patients. AB - INTRODUCTION: Trauma scores are often used for prognostication and the adjustment of mortality data. The appropriate consideration of identified prognostic factors is mandatory for a valid score with good outcome prediction properties. The Trauma Registry of the German Society for Trauma Surgery (TR-DGU) initially used the Trauma and Injury Severity Score (TRISS) but various reasons led to the development of a new scoring system, the Revised Injury Severity Classification (RISC). PATIENTS AND METHODS: A total of 2,008 severely injured patients with complete data documented in the TR-DGU during the period 1993-2000 were used to develop a new score. Patients were split into a development sample (n = 1,206) and a validation sample (n = 802). Multivariate logistic regression analysis was applied, and the results were compared with existing score systems. The quality of prediction was determined regarding discrimination (disparity, sensitivity, specificity, receiver operating characteristic [ROC] curve), precision (predicted versus observed mortality), and calibration (Hosmer-Lemeshow goodness-of-fit). RESULTS: Existing score systems (ISS, NISS, RTS, ASCOT, TRISS, Rixen) revealed areas under the ROC curve ranging from 0.767 to 0.877. The RISC combines 11 different components: age, NISS, head injury, severe pelvic injury, Glasgow Coma Scale, partial thromboplastin time (PTT), base excess, cardiac arrest, and indirect signs of bleeding (shock, mass transfusion, and low hemoglobin). The new RISC score reached significantly higher values of above 0.90 for the area under the ROC curve in both development and validation samples. Application to data from 2001 confirmed these results. CONCLUSION: Outcome prediction including initial laboratory values was able to significantly improve the ability to discriminate between survivors and nonsurvivors. The adjustment of mortality rates should be based on the best available prediction model. PMID- 26815210 TI - Five years experience of trauma care in a German urban level I university trauma center. AB - BACKGROUND: A regionalized approach to trauma care with the implementation of designated level I trauma centers has been shown to improve survival after multiple injuries. Our study aimed to describe the current reality in an urban German level I university trauma center concerning the primary admission of patients into the emergency room. MATERIALS AND METHODS: We performed a retrospective analysis of all multiple trauma patients that were prospectively documented in our documentation system TraumaWatch((r)) from 2003 to 2007. Documentation included physiological findings as well as diagnostic and therapeutic procedures structured as: (A) preclinical phase; (B) emergency room treatment; (C) intensive care unit; and (D) final outcome according to the German Trauma Registry. RESULTS: In total, 1,848 patients were completely documented and, thus, analyzed. The mean +/- standard deviation (SD) Injury Severity Score (ISS) was 16.5 +/- 14.1 points and the mean +/- SD age was 38.7 +/- 21.9 years. An increasing number of patients received whole-body computed tomography (48.8% in 2003 vs. 83.3%in 2007, p < 0.001) and, on average, the ISS increased over the years (14.4 points in 2003 vs. 17.9 points in 2007). The overall hospital mortality was 7.1%, without significant change over time. The completionofimagingdiagnostics became significantly faster for all of the documented procedures (X-ray pelvis, X-ray chest, whole-body CT, abdominal ultrasound) (p < 0.001). DISCUSSION: Descriptive data on the current reality in urban level I trauma care can be derived from our study. Additionally, we achieved improved time intervals for emergency diagnostics and treatment, while hospital mortality remained constant, despite a higher injury severity. This is due to a standardized protocol which is applied during the 24-h in-house attending coverage. CONCLUSION: Regionalized trauma care with designated level I trauma centers is justified by the improvement of time intervals and outcome, but adequate resources are required. PMID- 26815211 TI - Traumatic deaths in the emergency room: A retrospective analysis of 115 consecutive cases. AB - OBJECTIVE: The aim of the present study was to characterise traumatic deaths occurring in the emergency room (ER) and to assess retrospectively the quality of given emergency care by evaluating whether any of the deaths could be identified as potentially preventable. METHODS: All consecutive deaths of trauma patients between 1 January 1998 and 31 December 2006 in the ER of the Toolo Hospital Trauma Centre were retrospectively reviewed. The inclusion criterion was death of a trauma patient occurring in the ER. Both the pre- and inhospital medical charts and the autopsy reports of the patients were reviewed. RESULTS: A total of 115 patients fulfilled the inclusion criteria, and the autopsy reports were obtained for all of these cases (100%). The patients were mainly males (n = 84; 73%), and the median age of the patients was 51 years (range 1-93 years). The average injury severity score (ISS) was 34.6. Blunt trauma was the most common type of injury in the study population. A total of 115 injuries in 50 patients were missed in both the clinical and radiological surveys in the ER, i.e., a missed injury was identified in 43% of the cases. Of these patients, 15.7% had a clinically significant missed injury (AIS >= 4). Based on our review of all available material, we consider that 11 deaths (9.6%) were potentially preventable. CONCLUSIONS: Missed injuries did not play a major role in the preventable deaths. Seven potentially preventable deaths were considered to be failures in the surgical decision-making process, resulting in futile non operative treatment or a delay in surgical bleeding control. PMID- 26815212 TI - Role of lung contusions on posttraumatic inflammatory response and organ dysfunction in traumatized patients. AB - BACKGROUND: Multiple trauma is often accompanied by lung contusion leading to secondary pulmonary inflammation and organ dysfunction. The particular role of lung contusions on the systemic inflammatory response remains unclear. Therefore, the aim of the present study was to compare the degree of lung contusion with markers of inflammation and multiple organ failure (MOF) in trauma patients. METHODS: According to the Injury Severity Score (ISS), 45 patients were assigned to a low (< 25 points) and a high ISS group (> 25 points), respectively. Both groups were subdivided into minor and major lung injury groups as defined by computed tomography (CT) scan. Plasma levels of interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor (TNF) receptors, C-reactive protein (CRP), and polymorphonuclear (PMN) elastase were assessed, as well as the Murray lung score (MLS) and the MOF score. RESULTS: Patients with low ISS present moderate activation of inflammation which is not influenced by the degree of lung contusion. In contrast, patients with a high ISS develop significant posttraumatic inflammation and MOF. Patients with high ISS and severe lung contusions present significantly higher MLS and MOF scores. Interestingly, patients of the high ISS group without severe lung contusions develop a similar degree of MLS and MOF only after 5 days following the traumatic insult. However, the initial plasma levels of IL-6 and IL-8 differ significantly in this group. CONCLUSION: Our data show that severe lung contusions contributes to an immediate onset of posttraumatic inflammation in severely traumatized patients, resulting in MOF, while in severely injured patients without lung contusion, this development requires up to 5 days. PMID- 26815213 TI - Patient selection criteria for primary total hip Arthroplasty in displaced intracapsular hip fractures: Are they appropriate? AB - INTRODUCTION: This study aims to determine, by outcome analysis, the appropriateness of current criteria employed to select patients for total hip arthroplasty (THA) as the primary treatment for displaced intracapsular hip fracture (DICHF). This study is intended to inform prospective randomised controlled trials investigating the efficacy of THA as a primary treatment. MATERIALS AND METHODS: Contemporary THA eligibility criteria were derived from recent publications relating to pre-fracture residence, mobility and independence. Outcome data were analysed for 96 patients (19% of 506 consecutive patients with DICHF between March 2003 and February 2005) who fulfilled those criteria. The variables analysed included age, gender, co-existing injuries, co morbidities, social circumstances, mobility, independence, delay to surgery, readmission and death. The 96 patients included in the study were followed for 3 years. The primary outcome was the combined achievement of home or warden assisted accommodation at 3 months, no patient readmission within 6 weeks of discharge and survival to 1 year. Secondary outcome was survival to 3 years. RESULTS: At 3 months, 86 patients (90%) had returned home, three (3.1%) required nursing or residential home placement, four (4.2%) were still resident in a community hospital and three (3.1%) had died. A total of ten patients failed to return to their own home. Eight patients (8.3%) were readmitted within 6 weeks. At 1 year, eight patients (8.3%) had died; by 3 years, the mortality rate was 25%. Patients not achieving return to home were older (84.8 years vs. 79.7 years, p = 0.19), prior to fracture weremore likely to use a walking aid (odds ratio [OR] 2.35) or required home support (OR 1.74). The number of co-morbidities was not an association. Backward selection applied to the above data produced an OR of 1.12 (confidence interval [CI] 1.01-1.21) for age as a variable in patients successfully discharged home, so that for each increase in age by year, the odds of home not being the final destination increased by 12%. These factors were also reflected in the patients requiring readmission within 6 weeks from discharge. CONCLUSIONS: If maintaining a high level of activity and independence is the expectation in patients considered for THA for DICHFs, then current selection criteria appear to be appropriate in identifying those capable of returning home, remaining independent and surviving to 1 year compared to the whole DICHF population. With a 75% 3-year survival, the postulated benefit of THA will not be realised in many patients and this needs to be considered. Cost-effectiveness trials are required before broad practice change occurs. PMID- 26815214 TI - Treatment of nonunion of femoral neck fracture by valgus osteotomy in 33 cases. AB - In spite of advances in treatment, femoral neck fractures are complicated fractures with a relatively high incidence of nonunion. Between 1990 and 2004, 33 patients with nonunion of femoral neck fractures were treated by valgus osteotomy in our department. The mean age of patients at the time of operation was 38 years (range 16-60 years). Reasons for nonunion were implant failure in 21 and osteomalacia in two patients. The remaining ten patients were treated nonoperatively. Average neck-shaft angle was 109 degrees (78 degrees -125 degrees ), and the average shortening of the involved limb was 2.5 cm (0.5-4.5). After subtrochanteric valgus osteotomy, fracture healing occurred in 32 of 33 patients. The average time for healing was five months (range 3-8 months). Pain and limitation of motion improved remarkably, and the majority of patients did not need to use crutches. Postoperatively, the neckshaft angle was 140 degrees (125 degrees -160 degrees ), and shortening reduced to an average of 1 cm. Partial avascular necrosis of the femoral head developed in five patients after 6 12 months. Valgus osteotomy of the femur is a suitable procedure for treatment of femoral neck nonunion in young patients, since it is easy to perform and yields relatively good results. PMID- 26815215 TI - Iatrogenic femoral neck fracture during closed nailing of the femoral shaft fracture. AB - BACKGROUND: Intramedullary nails have become a popular implant in the management of femoral shaft fractures. The occurrence of a femoral neck fracture after closed intramedullary nailing is an exceptional complication of this technique that has been rarely reported in the literature. METHODS: We report a retrospective study to identify the possible causes that could produce a fracture of the femoral neck after nailing of the ipsilateral femur. RESULTS: A total of four neck fractures were identified in a series of 494 femoral shaft nailing, all of them not visible on the initial plain films. In two cases, the nail entry point was located lateral to the tip of the greater trochanter. In the other two cases, the entry point was located too medial to the greater trochanter, violating the superoexternal cortex of the femoral neck. CONCLUSION: The event of a femoral neck fracture during closed intramedullary nailing is an unusual complication that may be caused due to a technical mistake related to the location of the nail entry portal in the proximal femur. PMID- 26815216 TI - Management of blunt bowel and mesenteric injuries: Experience at the Alfred hospital. AB - BACKGROUND: The incidence of blunt bowel and mesenteric injury (BBMI) has increased recently in blunt abdominal trauma, possibly due to an increasing number of high-speed motor accidents and the use of seat belts. OBJECTIVE: Our aim was to identify the factors determining the time of surgical intervention and how they affect the outcome of the patient with BBMI. This was achieved by reviewing our experience as a major Victorian trauma service in the management of bowel and mesenteric injuries and comparing this to the experiences reported in the literature. METHODS: A retrospective study reviewing 278 consecutive patients who presented to the Alfred trauma center with blunt bowel and mesenteric injuries over a 6-year period. RESULTS: The patient cohort comprised 278 patients with BBMI (66% were male, 34% were female), of whom 80% underwent a laparotomy, 17% were treated conservatively and 3% were diagnosed post-mortem. In terms of time from admission to laparotomy, 67% were treated within 0-4 h, 9% within 4-8 h, 3% within 8-12 h, 10% within 12-24 h, 4% within 24-48 h and 7% at >48 h. A focused abdominal sonography for trauma (FAST) was performed in 86 patients, of whom 51% had a positive FAST, 44% had a negative FAST and 4% had an equivocal FAST. Overall, 13% of the patient cohort did not have a FAST. Computerized tomography (CT) scans were undertaken preoperatively in 68% of the patients, revealing free gas (22% of patients), bowel-wall thickening (31%), fat and mesenteric stranding or hematoma (38%) and free fluid with no solid organ injury (43%). CONCLUSION: The timing of surgical intervention in cases of BBMI is mostly determined by the clinical examination and the results of the helical CT scan findings. The FAST lacks sensitivity and specificity for identifying bowel and mesenteric trauma. A delayed diagnosis of > 48 h has a significantly higher bowelrelated morbidity but not mortality. PMID- 26815217 TI - Proximal humeral fractures and intramedullary nailing: Experience with a new nail system. AB - OBJECTIVES: The goal of this study was to evaluate fracture healing and alignment as well as functional outcome and complication risks after internal fixation with the intramedullary proximal humeral nail (PHN). This device shows promise for applications involving the reconstruction of the humeral shaft and head with minimal soft tissue stripping and for providing a locked, fixed-angle construct for secure fixation to permit controlled, early, and active rehabilitation. DESIGN: Prospective case-series. SETTING: Multicenter study in 11 trauma units. PATIENTS: One-hundred and fifty-one patients were treated for the same number of proximal humerus fractures. INTERVENTION: Open reduction and internal fixation with the intramedullary PHN. MAIN OUTCOME MEASUREMENTS: Occurrence of postoperative complications during and up to 1 year of follow-up. The patients were actively followed up for 1 year with radiological assessment to observe fracture healing, alignment, reduction, and necrosis and by functional outcome measurements, including Constant, Disabilities of the Arm, Shoulder and Hand (DASH), and Neer scores. RESULTS: A total of 113 patients (77% of 147 surviving patients) were available for the 1-year follow-up assessment, among whom 99% of all examined fractures had healed at this last time point. The range of motion (ROM) of the injured shoulder satisfactorily improved between all of the follow up periods and by 1 year, 84-92% (ratio of injured to healthy contralateral shoulder) capacity had been achieved for all movements. The Constant score had significantly increased at the 3- and 6-month follow-ups, and by the final 1-year examination, this score attained up to 89% of the contralateral side. The mean baseline DASH was 5.9, with 62% of the total patient population having a zero DASH score. DASH scores higher than the preinjury scores were only observed in patients > 90 years of age, with this score significantly increasing with a mean difference of five points at the 1-year follow-up. At this last examination time point, patients had also reached a "satisfactory" mean Neer score of 85. Intraoperative complications were few (i.e., only four cases were documented) and solely related to the surgical technique; these problems included perforation of the articular surface by the oblique bolt or incorrect positioning of an additional screw. Humeral head necrosis was not common, with only four cases observed. Implant/surgery complications occurred in 63% (30/48) of the patients and included 13 cases of "cut through" (secondary impaction of the humeral head), nine cases of perforation of the articular surface, and four cases of implant loosening. Only four deaths were reported, and all were considered to be purely related to the patient and not to their participation in this study. CONCLUSION: Nailing of proximal humeral fractures with the PHN is possible, but indication is limited to mainly A- and B-type fractures. The results of this multicenter study with many participating surgeons show that the operative technique is demanding and that the majority of documented complications are related to a violation of published basic technical steps during the operative procedure. PMID- 26815218 TI - A case of delayed diagnosis of a right-sided diaphragm rupture with a review of the literature. AB - Right-sided diaphragm rupture is one of the typical injuries found during a secondary or tertiary survey after a major blunt trauma. This is mainly due to the apparently normal aspect of primary X-rays of the thorax. A right-sided diaphragm rupture can cause severe atelectasis of the right lower lobe of the lung, due to a hepatothorax. We present a case of a delayed diagnosis of right sided diaphragm rupture, which was discovered by accident because of a new trauma. We review the literature on right-sided diaphragm rupture and its treatment. PMID- 26815219 TI - Blunt liver trauma from bean bag ammunition. AB - Police departments in Europe are increasingly using nonlethal weapons and/or ammunitions such as a bean bag to restrain and disable a person temporarily. A bean bag is a small nylon bag filled with metal balls that is fired from a shotgun and weighs approximately 50 g. It is successfully used in the United States by law enforcement personnel. This report describes a case in which use of a bean bag resulted in a contusion of the liver, which was treated conservatively. PMID- 26815220 TI - Pneumatosis intestinalis with gastric pneumatosis and hepatoportal venous gas in blunt abdominal trauma: A case report. AB - A case of transient pneumatosis intestinalis with gastric pneumatosis and hepatoportal venous gas following blunt abdominal trauma is described. The presence of intramural gas mostly implies intestinal necrosis, which needs emergent surgical exploration. This case demonstrates that conservative management with close clinical observation and follow-up computed tomography scan can be safely applied in selected cases of pneumatosis intestinalis with gastric pneumatosis and hepatoportal venous gas. PMID- 26815221 TI - Donor-acceptor bonding in novel low-coordinated compounds of boron and group-14 atoms C-Sn. AB - A summary of theoretical and experimental work in the area of low-coordinated compounds of boron and group-14 atoms C-Sn in the last decade is presented. The focus of the account lies on molecules EL2, E2L2 and E3L3, which possess dative bonds between one, two or three atoms E and sigma-donor ligands L that stabilize the atoms E through L->E donor-acceptor interactions. The interplay between theory and experiment provides detailed insight into the bonding situation of the molecules, which serves as guideline for the synthesis of molecules that possess unusual bonding motifs. PMID- 26815222 TI - o-Quinone Methides via Oxone-Mediated Benzofuran Oxidative Dearomatization and Their Intramolecular Cycloaddition with Carbonyl Groups: An Expeditious Construction of the Central Tetracyclic Core of Integrastatins, Epicoccolide A, and Epicocconigrone A. AB - The intramolecular cycloaddition of o-quinone methides (o-QMs) with a carbonyl group has been envisaged and executed successfully in the context of constructing the complex and rare [6,6,6,6]-tetracyclic core found in the integrastatins, epicoccolide A, and epicocconigrone A. These transient o-QMs were generated easily from the oxidative dearomatization of the corresponding C2 (aryl)benzofuran by employing Oxone in acetone-water at rt. The subsequent cycloaddition with the carbonyl (or conjugated olefin) present on the C2-aryl group was spontaneous. PMID- 26815223 TI - Biocompatible ELR-Based Polyplexes Coated with MUC1 Specific Aptamers and Targeted for Breast Cancer Gene Therapy. AB - The search for new and biocompatible materials with high potential for improvement is a challenge in gene delivery applications. A cell type specific vector made of elastin-like recombinamer (ELR) and aptamers has been specifically designed for the intracellular delivery of therapeutic material for breast cancer therapy. A lysine-enriched ELR was constructed and complexed with plasmid DNA to give positively charged and stable polyplexes. Physical characterization of these polyplexes showed a particle size of around 140 nm and a zeta potential of approximately +40 mV. The incorporation of MUC1-specific aptamers into the polyplexes resulted in a slight decrease in zeta potential but increased cell transfection specificity for MCF-7 breast cancer cells with respect to a MUC1 negative tumor line. After showing the transfection ability of this aptamer-ELR vector which is facilitated mainly by macropinocytosis uptake, we demonstrated its application for suicide gene therapy using a plasmid containing the gene of the toxin PAP-S. The strategy developed in this work about using ELR as polymeric vector and aptamers as supplier of specificity to deliver therapeutic material into MUC1-positive breast cancer cells shows promising potential and continues paving the way for ELRs in the biomedical field. PMID- 26815225 TI - International Skeletal Trauma Symposia : March 3-7 and 7-11, 2007 Flims, Switzerland. PMID- 26815224 TI - Clinical evaluations of mineralized collagen in the extraction sites preservation. AB - The purpose of this study was to explore the different effects between biomimetic mineralized collagen (MC) and ordinary physically blended hydroxyapatite/collagen (HA/Col) composite in evaluating new bone formation and regenerated bone height in human extraction sockets. Thirty-four patients who cannot retain teeth caused by trauma or decay were randomly selected from Department of Stomatology of Dongzhimen Hospital from December 2013 to December 2014. The patients were randomly divided into two groups. After the operation of tooth extraction, 17 patients were implanted with biomimetic MC (MC group), and other 17 patients were implanted with ordinary physically blended nHA/Col composite (nHA/Col group). X ray positioning projection by auto-photographing was taken to test the distance between the lowest position and the neighboring CEJm-CEJd immediately, 1 month and 3 months after the operation. The height of new bone formation of the MC group was significantly higher than the nHA/Col group. Biomimetic MC showed better clinical outcomes in the bone formation for extraction site preservation and would have broad application prospect in the field of oral and maxillofacial surgeries. PMID- 26815226 TI - Feed the gut, feed early and with the right stuff, but do not forget total parenteral nutrition. PMID- 26815227 TI - Nutrition therapy for critically ill and injured patients. AB - BACKGROUND: Nutrition support has undergone significant advances in recent decades, revolutionizing the care of critically ill and injured patients. However, providing adequate and optimal nutrition therapy for such patients is very challenging: it requires careful attention and an understanding of the biology of the individual patient's disease or injury process, including insight into the consequent changes in nutrients needed. OBJECTIVE: The objective of this article is to review the current principles and practices of providing nutrition therapy for critically ill and injured patients. METHODS: Review of the literature and evidence-based guidelines. RESULTS: The evidence demonstrates the need to understand the biology of nutrition therapy for critically ill and injured patients, tailored to their individual disease or injury, age, and comorbidities. CONCLUSION: Nutrition therapy for critically ill and injured patients has become an important part of their overall care. No longer should we consider nutrition for critically ill and injured patients just as "support" but, rather, as "therapy", because it is, indeed, a key therapeutic modality. PMID- 26815228 TI - Disease-specific nutrition therapy: one size does not fit all. AB - INTRODUCTION: The delivery of adequate nutrition is an integral part of the care of the critically ill surgical patient, and the provision of nutrition may have a greater impact on outcome than many other therapies commonly employed in the treatment of certain disease states. METHODS: A review of the existing literature was performed to summarize the evidence for utilizing disease-specific nutrition in critically ill surgical patients. RESULTS: Enteral nutrition, unless specifically contraindicated, is always preferable to parenteral nutrition. Methodological heterogeneity and conflicting results plague research in immunonutrition, and routine use is not currently recommended in critically ill patients. CONCLUSION: There is currently insufficient evidence to recommend the routine initial use of most disease-specific formulas, as most patients with the disease in question will tolerate standard enteral formulas. However, the clinician should closely monitor for signs of intolerance and utilize disease specific formulas when appropriate. PMID- 26815230 TI - Nutritional support in patients following damage control laparotomy with an open abdomen. AB - INTRODUCTION: Damage control laparotomy (DCL) and the open abdomen have been well accepted following either severe abdominal trauma or emergency surgical disease. As DCL is increasingly utilized as a therapeutic option, appropriate management of the post-DCL patient is important. Early caloric support by enteral nutrition (EN) in the critically ill patient improves wound healing and decreases septic complications, lung injury, and multi-system organ failure. However, following DCL, nutritional strategies can be challenging and, at times, even daunting. CONCLUSIONS: Even though limited data exist, the use of early EN following DCL seems safe, provided that the patient is not undergoing active resuscitation or the bowel is not in discontinuity. It is unknown as to whether EN in the open abdomen reduces septic complications, prevents enterocutaneous fistula (ECF), or alters the timing of definitive abdominal wall closure. Future investigation in a prospective manner may help elucidate these important questions. PMID- 26815229 TI - Gastrointestinal tract access for enteral nutrition in critically ill and trauma patients: indications, techniques, and complications. AB - BACKGROUND: Enteral nutrition (EN) is a widely used, standard-of-care technique for nutrition support in critically ill and trauma patients. OBJECTIVE: To review the current techniques of gastrointestinal tract access for EN. METHODS: For this traditional narrative review, we accessed English-language articles and abstracts published from January 1988 through October 2012, using three research engines (MEDLINE, Scopus, and EMBASE) and the following key terms: "enteral nutrition," "critically ill," and "gut access." We excluded outdated abstracts. RESULTS: For our nearly 25-year search period, 44 articles matched all three terms. The most common gut access techniques included nasoenteric tube placement (nasogastric, nasoduodenal, or nasojejunal), as well as a percutaneous endoscopic gastrostomy (PEG). Other open or laparoscopic techniques, such as a jejunostomy or a gastrojejunostomy, were also used. Early EN continues to be preferred whenever feasible. In addition, evidence is mounting that EN during the early phase of critical illness or trauma trophic feeding has an outcome comparable to that of full-strength formulas. Most patients tolerate EN through the stomach, so postpyloric tube feeding is not needed initially. CONCLUSION: In critically ill and trauma patients, early EN through the stomach should be instituted whenever feasible. Other approaches can be used according to patient needs, available expertise, and institutional guidelines. More research is needed in order to ensure the safe use of surgical tubes in the open abdomen. PMID- 26815231 TI - Influence of implant design on the method of failure for three implants designed for use in the treatment of intertrochanteric fractures: the dynamic hip screw (DHS), DHS blade and X-BOLT. AB - BACKGROUND: The dynamic hip screw (DHS) has been widely adopted as the implant of choice in the treatment of intertrochanteric fractures. There have been attempts over the years to improve on the DHS lag screw design in order to reduce failure in the form of "cut out". The purpose of this study was to investigate how two new design variations of the DHS, the DHS blade and the X-BOLT, behave within bone, and if these design modifications do indeed improve the fixation achieved and lead to a reduction in failure due to cut out. METHODS: "Pushout" tests were chosen as the means of investigating the failure modes and patterns for these implants that lead to cut out. These pushout studies were performed in artificial bone substrate in the form of polyurethane foam blocks and in cadaveric femoral heads. RESULTS: The results demonstrated that each individual implant produces its own specific distinct force-displacement curve or pattern of failure, and that despite the very different implant designs and methods of fixation, all of the implants tested reached very similar peak forces in each of the test materials used. CONCLUSION: The results demonstrated that implant design only influences the pattern of failure, and that the peak forces reached by each implant are determined by the quality of the bone or test material into which they are placed. However, altering the force-displacement curve or pattern of failure may be enough to improve the fixation achieved and to provide an increased resistance to cut out. PMID- 26815232 TI - Severe trauma of the chest wall: surgical rib stabilisation versus non-operative treatment. AB - BACKGROUND: Serial rib fractures and flail chest injury can be treated by positive-pressure ventilation. Operative techniques reduce intensive care unit (ICU) stay, overall costs, mortality and morbidity, as well as pain. The aim of this study was to evaluate the benefit of surgical rib stabilisation in comparison to non-operative treatment in patients with severe trauma of the chest wall. MATERIALS AND METHODS: From 2006 to 2011, the data of 44 patients with flail chest and serial rib fractures were collected retrospectively. A surgical group and an intensive care group with only intensive care therapy were formed. Rib and sternal fractures, flail chest, injury severity, thoracic injuries, mechanical ventilation, time in the ICU, overall hospital stay and mortality were evaluated. RESULTS: No postoperative surgical complications had been observed. The time under mechanical ventilation in the surgical group was 10.6 +/- 10.2 days, whereas in the non-surgical group, it was 13.7 +/- 13.7 days. Mechanical ventilation time after surgery was 6.9 +/- 6.5 days. Time in the ICU for the surgical group was 16.4 +/- 13.6 days, compared to the non-surgical group with 20.1 +/- 16.2 days. Postoperative time in the ICU was 11.7 +/- 10.3 days. The mortality in the surgical group was 10 % and in the non-surgical group it was 17 %. CONCLUSIONS: Operative rib stabilisation with plates is a safe therapy option for severe trauma of the chest wall. Provided that the duration of preoperative mechanical ventilation and time spent in the ICU is minimised due to early operation, our data suggest that the stabilisation of serial rib fractures and flail chest may lead to a reduced time of mechanical ventilation, time in the ICU and mortality. PMID- 26815233 TI - Mortality and quality of life after proximal femur fracture-effect of time until surgery and reasons for delay. AB - INTRODUCTION: Studies yield conflicting results from the effect of early surgery on mortality. Some observed a positive, others a negative and some did not find any effect of early operation. In this study, mortality and quality of life in relation to time until surgery as well as reasons for delay were observed prospectively. MATERIAL AND METHODS: Data of 138 patients (>65 years) with proximal femoral fractures and consecutive surgery were observed. Demographic data as well as mortality rate, survival time and Barthel Index up to 1 year in relation to different time frames were observed. Reasons for operative delay were divided into being administrative or patient-related. RESULTS: Three-month mortality was 10.1% and 1-years was 23.9%. Neither time from injury until hospital admission nor from injury until surgery or from hospital admission until surgery up to 48 hours had any effect on mortality and survival time. The age of patients dying in the follow-up period was significantly higher than the age of patients surviving (86.8 vs. 84.4 years). No influence of any delay in time until surgery on the Barthel Index was observed. CONCLUSION: In proximal femoral fractures, a delay of surgery up to 48 hours did not influence mortality and Barthel Index negatively, nor did other associating factors. Only the patients age at the time of injury influences mortality rate, survival time, and Barthel Index significantly. The older the patient at the time of injury; the higher the mortality rate, the shorter the survival time and the lower the Barthel Index. PMID- 26815234 TI - Contralateral extraaxial hematomas after urgent neurosurgery of a mass lesion in patients with traumatic brain injury. AB - PURPOSE: The development of a contralateral extraaxial hematoma has repeatedly been described in small series and descriptive studies. However, the evidence available to date is limited. OBJECTIVES: To evaluate the incidence and risk factors leading to the development of a contralateral extraaxial hematoma and to describe the characteristics of cases. METHODS: A retrospective cohort study with prospective data collection was undertaken. All patients admitted to an intensive care unit (ICU) from 2006 to 2010 were studied. The inclusion criteria were as follows: severe trauma [Injury Severity Score (ISS >= 16)], neurosurgery (NeuroSx) in the first 24 h. The following were excluded: subacute/chronic subdural hematomas, first bilateral NeuroSx. Cases were those who required immediate contralateral NeuroSx after the first NeuroSx due to the occurrence of a new extraaxial injury or significant growth of a previous one. Controls were those patients those who did not require second NeuroSx or who required reoperation due to ipsilateral lesions. The variables considered were: demographics, neurological assessment, traumatic injuries and severity, image and surgical findings, clinical course, and outcome. Statistics analysis comprised descriptive, inferential, and multivariate analysis by logistic regression. RESULTS: A total of 120 patients were included, among which there were 11 cases (incidence 9.2 %). The cases showed a significantly higher frequency of coma or severe traumatic brain injury (TBI) at admission, contralateral injury and contralateral skull fracture in the preoperative computed tomography (CT) scan, as well as decompressive craniectomy. There were no significant differences in the severity scores, clinical course, or outcomes. The presence of contralateral fracture was identified as an independent risk factor [relative risk (RR) 47.9, 95 % confidence interval (CI) 5.2-443]. CONCLUSIONS: Contralateral extraaxial hematoma is a rare entity, although it has a high mortality rate. Therefore, it requires a high index of suspicion, especially in patients with severe TBI, with minimal contralateral injury and mainly with contralateral skull fracture on the initial CT scan. PMID- 26815235 TI - Serum cleaved tau protein and traumatic mild head injury: a preliminary study in the Thai population. AB - PURPOSE: To determine the correlation between serum cleaved tau protein and traumatic mild head injury (MHI) (GCS 13-15). METHODS: A prospective observational study was conducted. Blood specimens from 12 healthy persons and 44 adult patients with traumatic MHI were collected in the emergency department to measure the cleaved tau protein level using a Human Tau phosphoSerine 396 ELISA kit. A brain computed tomography (CT) scan was done in all patients. The serum cleaved tau protein level was considered positive at a cut-off point of 0.1 pg/ml. An intracranial lesion was defined as any abnormality detected by brain CT scan. RESULTS: The mean age of the traumatic MHI patients was 34.9 +/- 15.6 years (range 15-74). The median GCS was 15. The median time from injury to arrival at the emergency department was 30 min. There were 11 intracranial lesions detected by brain CT scan (25.0 %). Serum cleaved tau protein was not detected in either healthy or traumatic MHI patients. CONCLUSION: As it was uncorrelated with traumatic MHI, serum cleaved tau protein proved to be an unreliable biomarker to use in the early detection of and decision-making for traumatic MHI patients at the emergency department. PMID- 26815236 TI - Does the ratio and thickness of prevertebral soft tissue provide benefit in blunt cervical spine injury? AB - PURPOSE: Although many reports advocate computed tomography (CT) as the initial surveillance tool for occult cervical spine injury (CSI) at the emergency department (ED), the role of a lateral cervical spine radiograph (LCSX) has still not been replaced. We hypothesized that the increased width of the prevertebral soft tissue on an LCSX provides helpful information for selecting the high-risk patients who need to be evaluated with more accurate diagnostic tools. METHODS: This was a retrospective and consecutive series of injured patients requiring cervical spine evaluation who were first imaged with three-view plain films at the ED. The prevertebral soft tissue thickness (PVST) and ratio of prevertebral soft tissue thickness to the cervical vertebrae diameter (PVST ratio) were calculated on the LCSX. Suspicion of CSI was confirmed by either CT or magnetic resonance imaging (MRI) scans. RESULTS: A total of 826 adult trauma patients requiring cervical spine evaluation were enrolled. The C3 PVST and PVST ratio were significantly different between patients with or without upper cervical area injury (UCAI, 8.64 vs. 5.49 mm, and 0.394 vs. 0.276, respectively), and, likewise, the C6 PVST and PVST ratio for patients with or without lower cervical area injury (LCAI, 16.89 vs. 14.66 mm, and 0.784 vs. 0.749, respectively). The specificity was greater than 90 % in predicting UCAI and LCAI when combining these two parameters. CONCLUSIONS: This method maximizes the usefulness of LCSX during the initial assessment of a conscious patient with blunt head and neck injury, especially for the identification of high-risk patients requiring prompt CT or MRI; on the other hand, it prevents the overuse of these high-cost imaging studies as initial diagnostic tools. PMID- 26815238 TI - ESTES News 3.2013. PMID- 26815237 TI - Erratum to: Gastrointestinal tract access for enteral nutrition in critically ill and trauma patients: indications, techniques, and complications. PMID- 26815239 TI - 32(nd) Meeting of the Pediatric Section of the German Society of Trauma Surgeons (DGU). PMID- 26815240 TI - Base J glucosyltransferase does not regulate the sequence specificity of J synthesis in trypanosomatid telomeric DNA. AB - Telomeric DNA of trypanosomatids possesses a modified thymine base, called base J, that is synthesized in a two-step process; the base is hydroxylated by a thymidine hydroxylase forming hydroxymethyluracil (hmU) and a glucose moiety is then attached by the J-associated glucosyltransferase (JGT). To examine the importance of JGT in modifiying specific thymine in DNA, we used a Leishmania episome system to demonstrate that the telomeric repeat (GGGTTA) stimulates J synthesis in vivo while mutant telomeric sequences (GGGTTT, GGGATT, and GGGAAA) do not. Utilizing an in vitro GT assay we find that JGT can glycosylate hmU within any sequence with no significant change in Km or kcat, even mutant telomeric sequences that are unable to be J-modified in vivo. The data suggests that JGT possesses no DNA sequence specificity in vitro, lending support to the hypothesis that the specificity of base J synthesis is not at the level of the JGT reaction. PMID- 26815242 TI - Reactivation of IgG-switched memory B cells by BCR-intrinsic signal amplification promotes IgG antibody production. AB - Secondary antibody responses are marked by faster kinetics, improved antibody affinity and a switch from IgM to other immunoglobulin isotypes, most notably IgG, compared with primary responses. These changes protect from reinfection and represent the principle of most vaccination strategies. Yet, the molecular mechanisms that underlie B-cell memory responses are unclear. Here we show, by inactivating the immunoglobulin tail tyrosine (ITT) signalling motif of membrane bound IgG1 in the mouse, that the ITT facilitates maintenance and reactivation of IgG-switched memory B cells in vivo. The ITT motif equips IgG-switched cells with enhanced BCR signalling capacity, which supports their competitiveness in secondary immune reactions and drives the formation of IgG-secreting plasma cells even in the absence of T-cell help. Our results demonstrate that ITT signalling promotes the vigorous production of IgG antibodies and thus provide a molecular basis for humoral immunological memory. PMID- 26815243 TI - Self-assembly of endohedral metallofullerenes: a decisive role of cooling gas and metal-carbon bonding. AB - The endohedral metallofullerene (EMF) self-assembly process in Sc/carbon vapor in the presence and absence of an inert cooling gas (helium) is systematically investigated using quantum chemical molecular dynamics simulations. It is revealed that the presence of He atoms accelerates the formation of pentagons and hexagons and reduces the size of the self-assembled carbon cages in comparison with analogous He-free simulations. As a result, the Sc/C/He system simulations produce a larger number of successful trajectories (i.e. leading to Sc-EMFs) with more realistic cage-size distribution than simulations of the Sc/C system. The main Sc encapsulation mechanism involves nucleation of several hexagons and pentagons with Sc atoms already at the early stages of carbon vapor condensation. In such proto-cages, both Sc-C sigma-bonds and coordination bonds between Sc atoms and the pi-system of the carbon network are present. Sc atoms are thus rather labile and can move along the carbon network, but the overall bonding is sufficiently strong to prevent dissociation even at temperatures around 2000 kelvin. Further growth of the fullerene cage results in the encapsulation of one or two Sc atoms within the fullerene. In agreement with experimental studies, an extension of the simulations to Fe and Ti as the metal component showed that Fe EMFs are not formed at all, whereas Ti is prone to form Ti-EMFs with small cage sizes, including Ti@C28-Td and Ti@C30-C2v(3). PMID- 26815244 TI - A Multivariable Prediction Model for the Chronification of Non-traumatic Shoulder Pain: A Systematic Review. AB - BACKGROUND: Shoulder pain is the third most common musculoskeletal complaint and many patients have an unfavorable outcome with long-term disability. Only 50% of all new episodes of shoulder pain show complete recovery within 6 months. Little is known about factors that contribute to chronicity of shoulder pain, although such information is needed for the management of patients with acute and sub acute shoulder pain. OBJECTIVE: To systematically review the literature for prognostic factors which are potential predictors for either recovery or chronification in patients with acute and sub-acute non-traumatic shoulder pain. STUDY DESIGN: Systematic review. SETTING: This systematic review examined all studies involving the prognosis of shoulder pain patients. METHODS: This systematic review was reported following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two reviewers independently scored the methodological quality of the selected studies. Due to heterogeneity of studies, a best-evidence synthesis of the available prognostic factors was provided. RESULTS: Nine studies met our inclusion criteria and were included in this systematic review. There is strong evidence that high scores on the Shoulder Pain and Disability Index (SPADI), high scores on shoulder pain severity, and a long duration of complaints are factors that contribute to the chronification of shoulder pain. Moderate evidence was found supportive for other prognostic factors that enhance chronification, like being male, being over 55 years of age, having poor general health, having a gradual onset of complaints, a large amount of sick leave, the perception of high job demand, the perception of low social support, and the amount of visits to a health care professional. Also moderate evidence exists regarding factors that contributed to a reduced possibility of chronification: an active treatment policy and not taking medication on regular basis. LIMITATIONS: The large variability in definitions of shoulder pain, and patient selection bias. In addition, there is a paucity of strong longitudinal prospective studies. CONCLUSION: This systematic review found evidence that high scores on the SPADI questionnaire, more shoulder pain, and a longer duration of complaints are associated with chronification of shoulder pain. In order to reduce chronification, clinicians can use the International Classification of Functioning based model presented here that could aid their decision-making. PMID- 26815245 TI - In errata. PMID- 26815246 TI - Palmitoylethanolamide, a Special Food for Medical Purposes, in the Treatment of Chronic Pain: A Pooled Data Meta-analysis. AB - BACKGROUND: A growing body of evidence suggests that neuroinflammation, which is characterized by infiltration of immune cells, activation of mast cells and glial cells, and production of inflammatory mediators in the peripheral and central nervous systems, has an important role in the induction and maintenance of chronic pain. These findings support the notion that new therapeutic opportunities for chronic pain might be based on anti-inflammatory and pro resolving mediators that act on immune cells, in particular mast cells and glia, to mitigate or abolish neuroinflammation. Among anti-inflammatory and pro resolving lipid mediators, palmitoylethanolamide (PEA) has been reported to down modulate mast cell activation and to control glial cell behaviors. OBJECTIVE: The aim of this study was to perform a pooled meta-analysis to evaluate the efficacy and safety of micronized and ultra-micronized palmitoylethanolamide (PEA) on pain intensity in patients suffering from chronic and/or neuropathic pain. STUDY DESIGN: Pooled data analysis consisting of double-blind, controlled, and open label clinical trials. METHODS: Double-blind, controlled, and open-label clinical trials were selected consulting the PubMed, Google Scholar, and Cochrane databases, and proceedings of neuroscience meetings. The terms chronic pain, neuropathic pain, and micronized and ultra-micronized PEA were used for the search. Selection criteria included availability of raw data and comparability between tools used to diagnose and assess pain intensity. Raw data obtained by authors were pooled in one database and analyzed by the Generalized Linear Mixed Model. The changes in pain over time, measured by comparable tools, were also assessed by linear regression post-hoc analysis and the Kaplan-Meier estimate. Twelve studies were included in the pooled meta-analysis, 3 of which were double blind trials comparing active comparators vs placebo, 2 were open-label trials vs standard therapies, and 7 were open-label trials without comparators. RESULTS: Results showed that PEA elicits a progressive reduction of pain intensity significantly higher than control. The magnitude of reduction equals 1.04 points every 2 weeks with a 35% response variance explained by the linear model. In contrast, in the control group pain, reduction intensity equals 0.20 points every 2 weeks with only 1% of the total variance explained by the regression. The Kaplan-Meier estimator showed a pain score = 3 in 81% of PEA treated patients compared to only 40.9% in control patients by day 60 of treatment. PEA effects were independent of patient age or gender, and not related to the type of chronic pain. LIMITATIONS: Noteworthy, serious adverse events related to PEA were not registered and/or reported in any of the studies. CONCLUSION: These results confirm that PEA might represent an exciting, new therapeutic strategy to manage chronic and neuropathic pain associated with neuroinflammation. PMID- 26815247 TI - MiDAS ENCORE: Randomized Controlled Clinical Trial Report of 6-Month Results. AB - BACKGROUND: Patients suffering from neurogenic claudication due to lumbar spinal stenosis (LSS) often experience moderate to severe pain and significant functional disability. Neurogenic claudication results from progressive degenerative changes in the spine, and most often affects the elderly. Both the MILD(r) procedure and epidural steroid injections (ESIs) offer interventional pain treatment options for LSS patients experiencing neurogenic claudication refractory to more conservative therapies. MILD provides an alternative to ESIs via minimally invasive lumbar decompression. STUDY DESIGN: Prospective, multi center, randomized controlled clinical trial. SETTING: Twenty-six US interventional pain management centers. OBJECTIVE: To compare patient outcomes following treatment with either MILD (treatment group) or ESIs (active control group) in LSS patients with neurogenic claudication and verified ligamentum flavum hypertrophy. METHODS: This prospective, multi-center, randomized controlled clinical trial includes 2 study arms with a 1-to-1 randomization ratio. A total of 302 patients were enrolled, with 149 randomized to MILD and 153 to the active control. Six-month follow-up has been completed and is presented in this report. In addition, one year follow-up will be conducted for patients in both study arms, and supplementary 2 year outcome data will be collected for patients in the MILD group only. OUTCOME MEASURES: Outcomes are assessed using the Oswestry Disability Index (ODI), numeric pain rating scale (NPRS) and Zurich Claudication Questionnaire (ZCQ). Primary efficacy is the proportion of ODI responders, tested for statistical superiority of the MILD group versus the active control group. ODI responders are defined as patients achieving the validated Minimal Important Change (MIC) of =10 point improvement in ODI from baseline to follow-up. Similarly, secondary efficacy includes proportion of NPRS and ZCQ responders using validated MIC thresholds. Primary safety is the incidence of device or procedure-related adverse events in each group. RESULTS: At 6 months, all primary and secondary efficacy results provided statistically significant evidence that MILD is superior to the active control. For primary efficacy, the proportion of ODI responders in the MILD group (62.2%) was statistically significantly higher than for the epidural steroid group (35.7%) (P < 0.001). Further, all secondary efficacy parameters demonstrated statistical superiority of MILD versus the active control. The primary safety endpoint was achieved, demonstrating that there is no difference in safety between MILD and ESIs (P = 1.00). LIMITATIONS: Limitations include lack of patient blinding due to considerable differences in treatment protocols, and a potentially higher non responder rate for both groups versus standard-of-care due to study restrictions on adjunctive pain therapies. CONCLUSIONS: Six month follow-up data from this trial demonstrate that the MILD procedure is statistically superior to epidural steroids, a known active treatment for LSS patients with neurogenic claudication and verified central stenosis due to ligamentum flavum hypertrophy. The results of all primary and secondary efficacy outcome measures achieved statistically superior outcomes in the MILD group versus ESIs. Further, there were no statistically significant differences in the safety profile between study groups. This prospective, multi-center, randomized controlled clinical trial provides strong evidence of the effectiveness of MILD versus epidural steroids in this patient population. CLINICAL TRIAL REGISTRATION: NCT02093520. PMID- 26815248 TI - Randomized Controlled Study of Percutaneous Epidural Neuroplasty Using Racz Catheter and Epidural Steroid Injection in Cervical Disc Disease. AB - BACKGROUND: The efficacy of lumbar percutaneous epidural neuroplasty (PEN) as a minimally invasive technique has been relatively well investigated, but the clinical effectiveness of cervical PEN (C-PEN) has yet to be established. OBJECTIVE: The purpose of this study was to compare clinical outcomes between C PEN and cervical epidural steroid injection (C-ESI). STUDY DESIGN: Randomized control study. SETTING: University hospital center. METHODS: Eighty patients with neck pain from single level cervical disease with and without radiculopathy were included in this study. Patients were randomly assigned into 2 groups: C-PEN or C ESI. Clinical outcomes were assessed according to Neck Disability Index (NDI) score and Visual Analog Scale (VAS) score for arm pain until 12 months after treatment. RESULTS: All C-PEN and C-ESI groups showed better NDI recovery and greater reduction in VAS score at postoperative 6 months (P < 0.001). The C-PEN group demonstrated better NDI score at postoperative 6 months than the C-ESI group (P = 0.014), while there were no differences at 2, 4, and 12 months. Additionally, the C-PEN group showed lower VAS scores at all follow-up intervals compared to the C-ESI group (P < 0.050). Symptom relief was sustained for a significantly longer duration in the C-PEN group than in the C-ESI group (23.4 vs. 20.5 weeks, P < 0.001). LIMITATIONS: The follow-up period was relatively short with a small sample size, and the grade of cervical disc disease, root compression, and disc degeneration grade were could not considered in this study. CONCLUSIONS: C-PEN was superior to C-ESI in terms of better NDI recovery (at 6 months) and greater reduction in VAS score (until 12 months) in treating single level cervical disc herniation. Better outcomes with C-PEN may have been achieved via a more localized selective block in the epidural space closer to the dorsal root ganglion and ventral aspect of the nerve root. PMID- 26815249 TI - Pulsed Radiofrequency Reduced Neuropathic Pain Behavior in Rats Associated with Upregulation of GDNF Expression. AB - BACKGROUND: Pulsed radiofrequency (PRF) is a novel nondestructive interventional technique for the treatment of neuropathic pain (NP). However, this intervention is still lack of relevant regulation and the mechanism of action is insofar not clear. Historically, most studies have reported that PRF can relieve reduce hyperalgesia in multiple NP animal models by acting on the dorsal root ganglion. However, a few recent studies have shown that PRF can effectively treat hyperalgesia in pain models by a direct application on injured peripheral nerves. OBJECTIVES: To observe changes in pain behavior and the pathology of the sciatic nerve (SN) after applying PRF at the ligation site in a chronic constriction injury (CCI) rat model and to investigate the effect of PRF on the expression of glia cell line-derived neurotrophic factor (GDNF) in nervous tissue. STUDY DESIGN: A randomized, experimental trial. SETTING: Experimental Animal Center, Beijing Tiantan Hospital, Capital Medical University. METHODS: Thirty-six adult Sprague-Dawley rats were randomly divided into 3 groups: Sham-Sham (SS), CCI-Sham (CS), and CCI-PRF (CP). The right SNs of the rats in the CS and CP groups were ligated to create a CCI model. For the SS group, the right SN was separated without ligation. On the 14th fourteenth day after surgery, PRF treatment was applied at the ligation site of the SN for the rats in the CP group using a 45 V output voltage at 42 degrees C for 3 minutes. The electrode was placed in rats in the SS and CS groups without electricity applied. The hindpaw withdrawal threshold (HWT) and thermal withdrawal latency (TWL) were measured at various time points before and after the treatments in each group. Optical microscopic scores and electron microscopic observation were given to the right SN ligation sites of the rats in each group 14 days after the treatment. Meanwhile, the GDNF expression levels in the ligation site of the SN and in the L4-L6 spinal cord segments were determined for each group by enzyme-linked immunosorbent assay (ELISA). RESULTS: Fourteen days after PRF treatment, the HWT and TWL values in the CP group were significantly increased compared to those of the CS group (P < 0.01). Under the optical microscope, the axonal number, axonal diameter, and myelin sheath thickness in the CP group were significantly increased compared to those of the CS group 14 days after PRF treatment (P < 0.01). Under the electron microscope, the degeneration at the SN ligation site was significantly improved in the CP group compared to the CS group. The GDNF expression levels at the ligation site of the SN and the L4-L6 spinal segments in the CP and CS groups were increased compared to those of the SS group (P < 0.01). In addition, the GDNF expression in the CP group was significantly higher than that in the CS group (P < 0.01). LIMITATIONS: GDNF expression was only measured at day 14 after the treatment rather than at various time points during the experiment. CONCLUSIONS: The findings suggest that the application of PRF at the impaired SN relieved reduced the CCI-induced NP by through regulating the upregulation of the GDNF expression in the nervous tissues. PMID- 26815250 TI - Exercise- and Stress-Induced Hypoalgesia in Musicians with and without Shoulder Pain: A Randomized Controlled Crossover Study. AB - BACKGROUND: Professional and pre-professional musicians are characterized by physical and psychological demands inherent to their musical activity, and therefore at risk for developing performance related musculoskeletal pain. Physical and psychological demands are known to influence human pain modulation. OBJECTIVES: In this study we compared the influence of a physically and emotionally stressful task on pain thresholds in musicians with and without shoulder pain. STUDY DESIGN: A single-blinded randomized and controlled crossover study design was used to compare the effects of a physical versus emotional testing procedure on pressure pain thresholds (PPTs) in musicians with and without shoulder pain. SETTING: All data were obtained in the field (e.g., at the physiotherapy accommodation in the Royal Conservatory). METHODS: During the physical testing procedure, the subjects performed an isometric exercise of the glenohumeral external rotators. The emotional task comprised watching "unpleasant" images selected from the International Affective Picture System. The outcome was the assessment of change in PPTs before and after the physical and emotional task. RESULTS: Our results indicate similar effects of both protocols in either group, i.e., musicians with and without shoulder pain (P > 0.05). All musicians showed elevated PPTs at local and remote areas after isometric exercise (P < 0.05). The emotional stress task increased PPTs at remote areas only (P < 0.05). LIMITATIONS: Despite the small sample size of musicians without shoulder pain, a power of 78.5% was achieved to detect the necessary effect size of Cohen's d = 1. Furthermore, comparing these results with those of non-musicians (both healthy subjects and patients with shoulder pain) might reveal information regarding the specific adaptations. Finally a high variability was observed in shoulder disability (i.e., SDQ-scores) as typically seen in a population with shoulder pain. CONCLUSIONS: In musicians with and without regional shoulder pain, no significant differences were found with respect to pain modulation during a physically and an emotionally stressful task. Both interventions adequately activated central and widespread pain inhibitory mechanisms in both groups. PMID- 26815251 TI - The Clinical Results of Percutaneous Endoscopic Interlaminar Discectomy (PEID) in the Treatment of Calcified Lumbar Disc Herniation: A Case-Control Study. AB - BACKGROUND: Percutaneous endoscopic interlaminar discectomy (PEID), which poses advantages for certain types of herniated disc, is gaining wider acceptance in clinical practice. We retrospectively analyzed the efficacy of the PEID technique in treatment of calcified lumbar disc herniation. STUDY DESIGN: A retrospective case-control study. SETTING: University hospital in China. OBJECTIVE: To evaluate the efficacy of the PEID technique in treatment of calcified lumbar disc herniation, and a comparison between calcified and noncalcified disc herniation was drawn to analyze the causes of herniated disc calcification. METHODS: Data from patients who underwent full-endoscopic lumbar discectomy in our department between March 2011 and May 2013 were collected. Thirty cases with calcified lumbar disc herniation were included in the study group, and 30 age-, gender-, and body mass index (BMI)-matched cases with noncalcified lumbar disc herniation served as controls. Perioperative data, preoperative and postoperative Visual Analog Scale (VAS) scores, Oswestry Disability Index (ODI) values, MacNab scores, and postoperative low-extremity dysesthesia among patients in the 2 groups were collected. RESULTS: The values of computed tomography (CT) in the calcified group were significantly higher than those in the noncalcified group (P < 0.01). The preoperative disease courses in the 2 groups were similar. However, there was a statistically significant difference in the duration of traditional Chinese medicines (TCM) administration (P < 0.01). VAS and ODI scores improved significantly after surgery, but there were no significant differences between the 2 groups (P > 0.05). Three months after surgery, the rate of low-extremity dysesthesia in the calcified group was significantly higher than that in the control group (P = 0.03) but became similar at 6 months. By applying MacNab criteria the proportions of good and excellent were greater than 90% in both groups, and there was no difference between groups (P > 0.05). LIMITATIONS: The sample size was small in this retrospective study. CONCLUSION: The PEID technique is an effective method in the treatment of calcified lumber disc herniation, although the rate of postoperative dysesthesia is higher in this group during the early postoperative period. Long-term TCM administration may be related to the calcification of herniated lumbar discs. PMID- 26815252 TI - Widespread Pressure Pain Hyperalgesia in Chronic Nonspecific Neck Pain with Neuropathic Features: A Descriptive Cross-Sectional Study. AB - BACKGROUND: Neck pain has an elevated prevalence worldwide. Most people with neck pain are diagnosed as nonspecific neck pain patients. Poor recovery in neck disorders, as well as high levels of pain and disability, are associated with widespread sensory hypersensitivity. Nevertheless, there is controversy regarding the presence of widespread hyperalgesia in chronic nonspecific neck pain (CNSNP); this lack of agreement could be due to the presence of different pathophysiological mechanisms in CNSNP. OBJECTIVES: To determinate differences in pressure pain thresholds (PPTs) over extracervical and cervical regions, and differences in cervical range of motion (ROM) between patients with CNSNP with and without neuropathic features (NF and No-NF, respectively). In addition, this study expected to observe correlations in these 2 types of CNSNP of psychosocial factors with PPTs and with cervical ROM separately. STUDY DESIGN: Descriptive, cross-sectional study. SETTING: A hospital physiotherapy outpatient department. METHODS: This research involved 53 patients with CNSNP that had obtained a Self completed Leeds Assessment of Neuropathic Symptoms and Signs pain scale (S-LANSS) score = 12 (pain with NF, NF group); 54 that had obtained a S-LANSS score < 12 (pain with No-NF, No-NF group), and 53 healthy controls (control group, CG). Measures included: PPTs (suboccipital muscle, upper fibers trapezius muscle, lateral epicondyle, and anterior tibial muscle), cervical ROM (flexion, extension, rotation, and latero-flexion), pain intensity (Visual Analog Scale [VAS]), neck disability index (NDI), kinesiophobia (Tampa Scale of Kinesiophobia 11 [TSK-11]), and Pain Catastrophizing Scale (PCS). RESULTS: A statistically significant effect was observed for the group factor in all assessed measures (P < 0.01). Both CNSNP groups showed statistically significant differences compared to the CG for PPTs in the cervical region (suboccipital and upper fibers trapezius muscles), but only the NF group demonstrated statistically significant differences for PPTs in the lateral epincondyle and anterior tibial muscle when compared to the CG or No-NF group. The largest statistically significant correlation found in the NF group was between PPT in the anterior tibial muscle and TSK-11 (r = -0.372; P < 0.01), while in the No-NF group it was between PPT in the suboccipital muscle and NDI (r = -0.288; P < 0.05). Statistically significant differences were found between the 2 CNSNP groups and CG in all cervical ROMs, but not between both CNSNP groups. The largest statistically significant correlation observed in the NF group was between cervical total rotation and TSK 11 (r = -0.473; P < 0.01), while in the No-NF group it was between cervical total latero-flexion and PCS (r = -0.532; P < 0.01). LIMITATIONS: Although the S-LANSS scale has been validated as a screening tool for pain with NF, currently there is no "gold standard," so these findings should be interpreted with caution. CONCLUSIONS: Widespread pressure pain hyperalgesia was detected in patients with CNSNP with NF, but not in patients with CNSNP with No-NF. Patients with CNSNP presented bilateral pressure pain hyperalgesia over the cervical region and a decreased cervical ROM compared to healthy controls. However, no differences were found between the 2 CNSNP groups. These findings suggest differences in the mechanism of pain processing between patients with CNSNP with NF and No-NF. PMID- 26815253 TI - Impact of Urine Drug Screening on No Shows and Dropouts among Chronic Pain Patients: A Propensity-Matched Cohort Study. AB - BACKGROUND: The last 2 decades have seen a substantial increase in both the prescription of opioids for managing chronic pain, and an increase in opioid related deaths in the US. Urine drug screening (UDS) is the de facto monitoring tool aimed at detecting and deterring opioid misuse. OBJECTIVE: We study whether administering UDS on pain patients influences post-screening behavior of no-shows and dropouts. STUDY DESIGN: Observational cohort study of electronic medical records. SETTING: Single urban academic pain-clinic. METHODS: A retrospective cohort comparison of patients receiving UDS versus those not receiving UDS was conducted on the entire sample as well as in the propensity score-matched samples in which matching was based on age, gender, pain-score, procedure-scheduled, systolic and diastolic blood pressure (BP), pulse, temperature, physician ID, year of visit, psychology referral, and opioid prescription in the first visit. In addition, we conducted within-subjects logistic-regression to study no-shows and non-proportional hazards survival modeling to study dropout. RESULTS: Analyses of 4,448 clinic visits by 723 pain patients indicated that UDS exposure in the first visit is associated with increased risk of no-show in the second visit (OR = 2.73, P < .0001); no-show rate was 10.24% for those without UDS compared to 23.75% for those with a UDS. Among those tested, the no-show rate was higher for those testing positive for illicit substances (34.57%) than for those testing negative (21.74%). These findings were replicated in 8 different propensity-score matched subsamples aimed at addressing potential non-random selection, as well as in within-subject analysis accounting for individual-level no-show propensity. Non-proportional hazards survival analysis shows that risk of dropout increased by 100.3% with every additional UDS (HR 95% CI: 1.54 to 2.61). LIMITATIONS: Retrospective design, non-randomized sample, single-setting. CONCLUSIONS: The results indicate that UDS is associated with increased no-shows and dropout from clinic subject to limitations of observational studies such as selection bias and confound by unobserved variables. These results serve as a call for additional prospective randomized studies to understand the impact of UDS, and where the patients might go when they dropout from the clinic. PMID- 26815254 TI - Percutaneous and Endoscopic Adhesiolysis in Managing Low Back and Lower Extremity Pain: A Systematic Review and Meta-analysis. AB - BACKGROUND: Chronic refractory low back and lower extremity pain is frustrating to treat. Percutaneous adhesiolysis and spinal endoscopy are techniques which can treat chronic refractory low back and lower extremity pain.Percutaneous adhesiolysis is performed by placing the catheter into the tissue plane at the ventrolateral aspect of the foramen so that medications can be injected. Adhesiolysis is used both for pain caused by scarring which is not resistant to catheter placement and other sources of pain, including inflammation in the absence of scarring.Mechanical lysis of scars with a catheter may or may not be necessary for percutaneous adhesiolysis to be effective. Spinal endoscopy allows direct visualization of the epidural space and has the possibility to use laser energy to treat pathology. STUDY DESIGN: A systematic review of the effectiveness of percutaneous adhesiolysis and spinal endoscopic adhesiolysis to treat chronic refractory low back and lower extremity pain. OBJECTIVE: To evaluate and update the effectiveness of percutaneous adhesiolysis and spinal endoscopic adhesiolysis to treat chronic refractory low back and lower extremity pain. METHODS: The available literature on percutaneous adhesiolysis and spinal endoscopic adhesiolysis in treating persistent low back and leg pain was reviewed. The quality of each article used in this analysis was assessed. The level of evidence was classified on a 5-point scale from strong, based upon multiple randomized controlled trials to weak, based upon consensus, as developed by the U.S. Preventive Services Task Force (USPSTF) and modified by ASIPP. Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to September 2015, and manual searches of the bibliographies of known primary and review articles. OUTCOME MEASURES: Pain relief of at least 50% and functional improvement of at least 40% were the primary outcome measures. Short term efficacy was defined as improvement of 6 months or less; whereas, long-term efficacy was defined more than 6 months. RESULTS: For this systematic review, 45 studies were identified. Of these, for percutaneous adhesiolysis there were 7 randomized controlled trials and 3 observational studies which met the inclusion criteria. For spinal endoscopy, there was one randomized controlled trial and 3 observational studies. Based upon 7 randomized controlled trials showing efficacy, with no negative trials, there is Level I or strong evidence of the efficacy of percutaneous adhesiolysis in the treatment of chronic refractory low back and lower extremity pain. Based upon one high-quality randomized controlled trial, there is Level II to III evidence supporting the use of spinal endoscopy in treating chronic refractory low back and lower extremity pain. CONCLUSION: The evidence is Level I or strong that percutaneous adhesiolysis is efficacious in the treatment of chronic refractory low back and lower extremity pain. Percutaneous adhesiolysis may be considered as a first-line treatment for chronic refractory low back and lower extremity pain. The evidence is Level II to III that spinal endoscopy is effective in the treatment of chronic refractory low back and lower extremity pain. KEY WORDS: Spinal pain, chronic low back pain, post lumbar surgery syndrome, epidural scarring, adhesiolysis, endoscopy, radicular pain. PMID- 26815255 TI - Can Repeat Injection Provide Clinical Benefit in Patients with Lumbosacral Diseases When First Epidural Injection Results Only in Partial Response? AB - BACKGROUND: Epidural steroid injection (ESI) is known to be an effective treatment for lower back or radicular pain due to herniated intervertebral disc (HIVD) and spinal stenosis (SS). Although repeat ESI has generally been indicated to provide more pain relief in partial responders after a single ESI, there has been little evidence supporting the usefulness of repeat injections in cumulative clinical pain reduction. OBJECTIVES: The purpose of this study was to determine whether repeat ESI at a prescribed interval of 2 to 3 weeks after the first injection would provide greater clinical benefit in patients with partial pain reduction than that provided by intermittent injection performed only when pain was aggravated. STUDY DESIGN: An Institutional Review Board (IRB)-approved retrospective chart review. SETTING: Spine hospital. METHODS: Two hundred and four patients who had underwent transforaminal ESI (TFESI) for treatment of lower back and radicular pain due to HIVD or SS and could be followed-up for one year were enrolled. We divided the patients into 2 groups. Group A (N = 108) comprised partial responders (NRS = 3 after first injection) who underwent repeat injection at a prescribed interval of 2 to 3 weeks after the first injection. Group B (N = 96) comprised partial responders who did not receive a repeat injection at the prescribed interval, but received repeat injections only for aggravation of pain. Various clinical data including total number of injections during one year, duration of NRS < 3 during one year (NRS < 3 duration), and time interval until aggravation of pain required additional injections after repeat injection in group A, or after first injection in group B (time to reinjection), were assessed. These data were compared between groups A and B in terms of total population, HIVD, and SS. RESULTS: In the whole population, the mean time to reinjection was 6.09 +/- 3.02 months in group A and 3.69 +/- 2.07 months in group B. The NRS < 3 duration was 9.72 +/- 2.86 months and 6.2 +/- 2.61 months in groups A and B, respectively. In HIVD patients, the mean time to reinjection was 5.82 +/- 3.23 months in group A and 3.84 +/- 2.34 months in group B, and NRS < 3 duration was 9.40 +/- 3.34 months and 7.15 +/- 2.40 months in groups A and B, respectively. In SS patients, the mean time to reinjection was 6.40 +/- 2.85 months in group A and 3.59 +/- 1.88 months in group B, and NRS < 3 duration was 9.98 +/- 2.41 months and 5.52 +/- 2.55 months in groups A and B, respectively. Group A had a significantly longer time to reinjection and longer NRS < 3 duration than group B in the whole population, HIVD, and SS. LIMITATION: Retrospective design. CONCLUSIONS: Repeat TFESI conducted at 2- to 3-week intervals after the first injection in partial responders contributed to greater clinical benefit compared to intermittent TFESI performed only upon pain aggravation. These benefits were observed in patients with HIVD and in those with SS, irrespective of severity or location of disease. PMID- 26815256 TI - Percutaneous Endoscopic Lumbar Discectomy as an Alternative to Open Lumbar Microdiscectomy for Large Lumbar Disc Herniation. AB - BACKGROUND: Remarkable advancements in endoscopic spinal surgery have led to successful outcomes comparable to those of conventional open surgery. Large lumbar disc herniation (LLDH) is a serious condition, resulting in higher surgical failure when accessing the herniated disc. OBJECTIVES: This study compared the outcomes of LLDH treated with percutaneous endoscopic lumbar discectomy (PELD) and open lumbar microdiscectomy (OLM). STUDY DESIGN: Retrospective assessment. METHODS: This retrospective observational study was conducted from January 2011 to June 2012. Forty-four consecutive patients diagnosed with LLDH without cauda equina syndrome who were scheduled to undergo spinal surgery were included. LLDH was defined as herniated disc fragment occupying > 50% of the spinal canal. Clinical outcomes were evaluated using a visual analogue scale (VAS, 0 - 10), functional status was assessed using the Oswestry Disability Index (ODI, 0 - 100%) at 1, 6, and 24 months postoperatively and surgical satisfaction rate (0 - 100%) at final follow up. Radiological variables were assessed by plain radiography. RESULTS: Forty-three patients were included; 20 and 23 patients underwent PELD and OLM, respectively. Both groups exhibited significant improvements in leg and back pain postoperatively (P < 0.001). Although there was no significant difference in leg pain improvement between the groups, improvement in back pain was significantly higher in the PELD group than in the OLM group (4.9 +/- 1.5 vs. 2.5 +/- 1.0, P < 0.001). The surgical satisfaction rate of the PELD group was significantly higher than that of the OLM group (91.3% +/- 6.5 vs. 84.3% +/- 5.2, P < 0.001). Mean operating time, hospital stay, and time until return to work were significantly shorter in the PELD group than in the OLM group (67.8 vs. 136.7 minutes, 1.5 vs. 7.2 days, and 4.2 vs. 8.6 weeks; P < 0.001). Disc height (%) decreased significantly from 23.7 +/- 3.3 to 19.1 +/- 3.7 after OLM (P < 0.001), but did not change significantly after PELD (23.6 +/- 3.2 to 23.4 +/- 4.2; P = 0.703). The segmental angle of the operated level increased from 10.3 degrees to 15.4 degrees in the PELD group, which was significantly higher than that in the OLM group (9.6 degrees to 11.6 degrees ; P = 0.038). In the OLM group, there was one case of fusion due to instability. In the PELD group, one case required revision surgery and another case experienced recurrence. There were no perioperative complications in either group. LIMITATION: The study was retrospective with a small sample size and short follow-up period. CONCLUSION: PELD can be an effective treatment for LLDH, and it is associated with potential advantages, including a rapid recovery, improvements in back pain, and disc height preservation. PMID- 26815257 TI - Percutaneous Endoscopic Lumbar Discectomy for L5-S1 Disc Herniation: Consideration of the Relation between the Iliac Crest and L5-S1 Disc. AB - BACKGROUND: Percutaneous transforaminal techniques for the treatment of lumbar disc herniation have markedly evolved. Percutaneous endoscopic lumbar discectomy (PELD) for L5-S1 disc herniation is regarded as challenging due to the unique anatomy of the iliac crest, large facet joint, and inclinatory disc space. Among these, the iliac crest is considered a major obstacle. There are no studies regarding the height of the iliac crest and their appropriate procedures in PELD. OBJECTIVES: This study discusses PELD for L5-S1 disc herniation and the appropriate approach according to the height of iliac crest. STUDY DESIGN: Retrospective evaluation. METHODS: 100 consecutive patients underwent PELD via the transforaminal route for L5-S1 disc herniation by a single surgeon. The study was divided into 2 groups: the foraminoplasty group requiring foraminal widening to access the herniated disc and the non-foraminoplasty group treated by conventional posterolateral access. Radiological parameters such as iliac height, the relative position of the iliac crest to the landmarks of the L5-S1 level, iliosacral angle and foraminal height, and disc location were considered. Clinical outcomes were assessed by the Visual Analogue Scale (VAS, 0 - 10) for back and leg pain, the Oswestry Disability Index (ODI, 0 - 100%), and the modified MacNab criteria. RESULTS: The overall VAS scores for back and leg pain decreased from 6.0 to 2.3 and from 7.5 to 1.7. The mean ODI (%) improved from 54.0 to 11.6. Using modified MacNab criteria, a good outcome was 92%. Foraminoplasty was required in 19 patients. Iliac crest height was significantly higher in the foraminoplasty group than the non-foraminoplasty group (37.7 mm vs 30.1 mm, P < 0.001). In the foraminoplasty group, the iliac crest is above the mid L5 pedicle on lateral radiography in all cases. There were no significant differences in foraminal height, foraminal width, iliosacral angle, or disc height between the 2 groups. In addition, there were no differences in clinical outcome between the 2 groups. LIMITATIONS: This study is a retrospective analysis and simplifies the complexity of the L5-S1 level and iliac bone using two dimensional radiography. CONCLUSION: In high iliac crest cases where the iliac crest is above the mid L5 pedicle in lateral radiography, foraminoplasty may be considered for transforaminal access of L5-S1 disc herniation. Conventional transforaminal access can be utilized with ease in low iliac crest cases where the iliac crest is below the mid-L5 pedicle. PMID- 26815258 TI - Ultrasound Guided Intercostobrachial Nerve Blockade in Patients with Persistent Pain after Breast Cancer Surgery: A Pilot Study. AB - BACKGROUND: Persistent pain after breast cancer surgery (PPBCS) affects 25 - 60% of breast cancer survivors and damage to the intercostobrachial nerve (ICBN) has been implicated as the cause of this predominantly neuropathic pain. Local anesthetic blockade of the ICBN could provide clues to pathophysiological mechanisms as well as aiding diagnosis and treatment of PPBCS but has never been attempted. OBJECTIVES: To assess the feasibility of ICBN blockade and assess its effects on pain and sensory function in patients with PPBCS. STUDY DESIGN: This prospective pilot study was performed in 2 parts: Part 1 determined the sonoanatomy of the ICBN and part 2 examined effects of the ultrasound-guided ICBN blockade in patients with PPBCS. SETTING: Section for Surgical Pathophysiology at Rigshospitalet, Copenhagen, Denmark. METHODS: Part 1: Sixteen unoperated, pain free breast cancer patients underwent systematic ultrasonography to establish the sonoanatomy of the ICBN. Part 2: Six patients with PPBCS who had pain in the axilla and upper arm were recruited for the study. Summed pain intensity (SPI) scores and sensory function were measured before and 30 minutes after the block was administered. SPI is a combined pain score of numerical rating scale (NRS) at rest, movement, and 100kPa pressure applied to the maximum point of pain using pressure algometry (max = 30). Sensory function was measured using quantitative sensory testing, which consisted of sensory mapping, thermal thresholds, suprathreshold heat pain perception as well as heat and pressure pain thresholds. The ICBN block was performed under ultrasound guidance and 10 mL 0.5% bupivacaine was injected. OUTCOME ASSESSMENT: The ability to perform the ICBN block and its analgesic and sensory effects. RESULTS: Only the second intercostal space could be seen on ultrasound which was adequate to perform the ICBN block. The mean difference in SPI was -9 NRS points (95%CI: -14.1 to -3.9), P = 0.006. All patients had pre-existing areas of hypoesthesia which decreased in size in 4/6 patients after the block. LIMITATIONS: The main limitation of this pilot study is its small sample size, but despite this, a statistically significant effect was observed. CONCLUSION: We have successfully managed to block the ICBN using ultrasound guidance and demonstrated an analgesic effect in patients in PPBCS calling for placebo-controlled studies. PMID- 26815259 TI - Clinical and Histological Effects of the Intrathecal Administration of a Single Dose of Dexmedetomidine in Rabbits. AB - BACKGROUND: There is experimental evidence that dexmedetomidine has neuroprotective effects. So, it could be expected that its intrathecal or epidural administration presents no harm. However, whether dexmedetomidine is neurotoxic to the spinal cord remains to be fully elucidated. OBJECTIVE: To evaluate the effect of preservative-free dexmedetomidine administered as a subarachnoid single injection on the spinal cord and meninges of rabbits. STUDY DESIGN: Research article. SETTING: Experimental research laboratory. METHODS: Twenty young adult female rabbits, each weighing between 3200 and 4900 g, and having a spine length between 36 and 40 cm, were divided by lot into 2 groups (G): 0.9% saline in G1 and preservative-free dexmedetomidine in G2 (dose of 10 ug). After intravenous anesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance, and a random 5 ul.cm-1 of spinal length (0.2 mL) of solution (saline or dexmedetomidine) was injected. The animals remained in captivity for 21 days under medical observation and were sacrificed by decapitation. The lumbosacral spinal cord portion was removed for immunohistochemistry to assess the glial fibrillary acidic protein (GFAP), and histology was assessed using hematoxylin and eosin (HE) stain. RESULTS: None of the animals had impaired motor function or decreased nociception during the period of clinical observation. None of the animals from the control group showed signs of injuries to meninges. In the dexmedetomidine group, however, 9 animals presented with signs of meningeal injury. The main histological changes observed were areas with meningeal thickening and lymphoplasmocitary infiltration in the pia-mater and arachnoid. Further histological examination also revealed adherence areas among the pia and arachnoid. There was no signal of injury in neural tissue in any animal of both groups. LIMITATIONS: Evaluation of the possible analgesic effects of the intrathecal dexmedetomidine was not performed. CONCLUSION: On the basis of the present results, dexmedetomidine administered in the subarachnoid space in a single dose of 10 ug is capable of producing histological changes over the meninges of rabbits. PMID- 26815260 TI - Fluoroscopy-Guided Sacroiliac Joint Injection: Description of a Modified Technique. AB - Sacroiliac joint (SIJ) pathology is a common etiologic cause for 10 - 27% of cases of mechanical low back pain (LBP) below the L5 level. In the absence of definite clinical or radiologic diagnostic criteria, controlled blocks of the SIJ have become the choice assessment method for making the diagnosis of SIJ pain. The SI joint is most often characterized as a large, auricular-shaped, diarthrodial synovial joint. In reality, its synovial characteristic is limited only to the distal third and anterior third. In SIJ interventions, the lateral view has been underutilized. In our technique, we used the lateral view to create a three-dimensional view of the SIJ to aid in gauging the accurateness of the contrast spread and to obtain a precise block. After obtaining appropriate fluoroscopic images, a curved tip spinal needle was directed into the inferior aspect of the SIJ using a posterior approach. As the needle contacts firm tissues on the posterior aspect of the joint, position of the needle tip is checked using lateral fluoroscopy. In the lateral view, the needle tip position is manipulated to keep it in the anterior third of the SIJ and contrast is injected. Our criteria for accurate SIJ block, in posteroanterior (PA) view, is the injection of the contrast medium should outline the joint space and the contrast medium should be seen to travel cephalad along the joint line. In the lateral view, the contrast medium most densely outlines the parameter of the joint. We have utilized this method with good effect in approximately 30 cases over one year. Out of 30 cases, needle position and contrast spread was satisfactory in 28 and 27 cases, respectively. So satisfactory needle placement and contrast spread was in 93% and 87% cases. Pain relief of 80% or more after intra-articular injection of local anesthetic was seen in 50% (15 of 30) patients; pain relief of 50 - 79% was witnessed in 30% (9 of 30) patients. Thus, pain decreased 50% or more in 80% (24 of 30) of the joints. Out of 24 joints where we got satisfactory needle position and contrast spread, 23 joints got more than 50% relief. Thus, if needle position and contrast spread is satisfactory as per the criteria, pain relief of 50% or more was in 96% (23 of 24) of joints. There are few possible limitations with this study like difficulty to go up to the anterior third of the SIJ, it may be more painful as a narrow joint line has to be travelled in depth, sciatic numbness due to drug leak, or injuring the pelvic structure. Advantages of this method are that depth and level of the needle tip for a SIJ block is described for the more precise block. This will reduce false positive and false negative results, i.e., sensitivity and specificity of SIJ blocks and results for diagnostic blocks become more reliable. It will also reduce the chances of a case getting abandoned due to inappropriate contrast spread obscuring the fluoroscopic landmarks. As we know the depth of the needle, the chances of injuring pelvic structures become less and safety improves. PMID- 26815261 TI - Endoscopic Retrieval of a Broken Guidewire During Spinal Surgery. AB - Since the percutaneous posterolateral approach in treating lumbar disc herniation was introduced in 1973, percutaneous endoscopic lumbar discectomy (PELD) has become a routine minimally invasive spinal procedure. However, as clinical evidence accumulated, several complications of PELD have raised our concerns, including the intraoperative injury to neural, vascular structures and failure of surgery. Herein, we present 2 patients who experienced guidewire breakage during PELD procedure to demonstrate the details.The 2 patients, who are 28 and 33 years old, were diagnosed with lumbar disc herniation with or without intervertebral foreman stenosis by magnetic resonance imaging. Following a preoperative evaluation, a PELD procedure was performed with the help of local anesthesia. During the advancement of the obturator and foraminotomy under fluoroscopy, the guidewire was found broken. With the patients permission, the operator inserted the working cannula to the broken end of the guidewire and retrieved it by straight grasping forceps under endoscopy. The patients were reported to recover from their back pain immediately after the operation and hence the postoperative course was stable.In conclusion, the guidewire breakage in PELD procedures is a rare but severe complication, which requires immediate removal. An appropriate manner and fluoroscopic control are recommended to forestall such problems. It is. PMID- 26815262 TI - Intrathecal Pump Exposure to Electromagnetic Interference: A Report of Device Interrogation following Multiple ECT Sessions. AB - BACKGROUND: Intrathecal drug delivery systems represent an increasingly common treatment modality for patients with a variety of conditions, including chronic pain and spasticity. Pumps rely on electronic programming to properly control and administer highly concentrated medications. Electromagnetic interference (EMI) is a known exposure that may cause a potential patient safety issue stemming from direct patient injury, pump damage, or changes to pump operation or flow rate. OBJECTIVES: The objective of our case report was to describe an approach to evaluating a patient with a pump prior to and following exposure to EMI from electroconvulsive therapy (ECT), as well as to document findings from device interrogations associated with this event. STUDY DESIGN: Case report. SETTING: Academic university-based pain management center. RESULTS: We present the case of a patient with an intrathecal pump who underwent multiple exposures to EMI in the form of 42 ECT sessions. Interrogation of the intrathecal drug delivery system revealed no safety issues following ECT sessions. At no time were error messages, unintentional changes in event logs, unintentional changes in pump settings, or evidence of pump stall or over-infusion noted. CONCLUSION: Communication with multiple entities (patient, family, consulting physicians, and device manufacturer) and maintaining vigilance through device interrogation both before and after EMI exposure are appropriate safeguards to mitigate the risk and detect potential adverse events of EMI with intrathecal drug delivery systems. Given the infrequent reports of device exposure to ECT, best practices may be derived from experience with EMI exposure from magnetic resonance imaging (MRI). Although routine EMI exposure to intrathecal drug delivery systems should be avoided, we describe one patient with repeated exposure to ECT without apparent complication. PMID- 26815263 TI - rTMS in Alleviating Mild TBI Related Headaches--A Case Series. AB - BACKGROUND: Headache is one of the most common debilitating chronic pain conditions in patients with mild traumatic brain injury. Conventional pharmacological treatments have not been shown to be effective in alleviating debilitating mild traumatic brain injury related headaches (MTBI-HA). Therefore, the development of an innovative non-invasive therapy in managing MTBI-HA is needed in the field of pain management. Repetitive transcranial magnetic stimulation (rTMS) utilizes a basic electromagnetic coupling principle in which a rapid discharge of electrical current is converted into dynamic magnetic flux, allowing the induction of a localized current in the brain for neuromodulation. The treatment is currently FDA approved for treating depression in the United States. Recent meta-analysis studies have implicated its usage in chronic pain management. OBJECTIVE: The objective of the prospective case series is to assess the potential application of rTMS in alleviating MTBI-HA. STUDY DESIGN: A prospective evaluation was conducted in patients with established diagnoses of MTBI-HA and treated with neuronavigational guided rTMS. SETTING: The study was conducted at the Veteran Administration San Diego Healthcare System where over 400 patients with MTBI were being evaluated annually by the Rehabilitation Medicine Service. A fraction of this patient population was referred and evaluated in the Anesthesia Pain Clinic for the consideration of rTMS for their headaches. METHODS: A prospective case series was conducted with human subject protection committee approval. Patients with established diagnoses of MTBI and constant headaches rated at = 4 on a 0 - 10 Numerical Rating Pain Scale (NRPS), and on stable headache medication regimens were selected to receive the treatment. Four sessions of rTMS were delivered to specific areas of cortices over a 2-month period. Patients' average intensities of lingering constant headaches (defined as duration of headache lasting more than 48 hours), and the average frequency (number of severe headache episodes per day), intensity (NRPS), and duration (hours) of headache exacerbations were assessed before and after the rTMS treatment protocol. RESULTS: Six men (average age of 50) with MTBI-HA received the rTMS treatment protocol. Average pre and post-rTMS constant headache scores (+/- SD) on the NRPS were 5.50 (+/- 1.38) and 2.67 (+/- 1.75), respectively, with an average post-rTMS headache intensity reduction of 53.05% (+/- 19.90). The average headache exacerbation frequency (episodes per week) was reduced by 78.97% (+/-19.88) with 2 patients reporting complete cessation of severe headache episodes. For those (N = 4) with persistent headache exacerbations, the average duration and intensity of these exacerbations were reduced by 50.0% and 31.7%, respectively. LIMITATIONS: This prospective evaluation provides the initial insight that rTMS may be beneficial in alleviating a debilitating chronic pain condition in patients with MTBI-HA. More controlled randomized studies should be conducted to validate its efficacy. Other co-existing cognitive and mood dysfunction should be assessed as well. CONCLUSIONS: rTMS offers a non-invasive treatment option for MTBI-HA. The tested treatment protocol was well tolerated by the patients and can be adopted for future randomized controlled studies in further validating the treatment efficacy. PMID- 26815264 TI - Ultrasound-Guided Diagnosis and Treatment of Morton's Neuroma. AB - Morton's neuroma is the fibrous enlargement of the interdigital nerve branches, usually in the second and third interspace between the metatarsal heads where the lateral and medial plantar nerves often join. Specific symptoms are dull or sharp pain, numbness and/or tingling in the third and fourth digits, burning sensation, cramping, and a feeling of "walking on a stone" around the metatarsal heads. Numerous clinical tests for Morton's neuroma have been described, such as thumb index finger squeeze, and Mulder's click and foot squeeze tests. Ultrasound and magnetic resonance imaging can be used for confirmation, especially for differential diagnosis, exact localization, and number of neuromas. Further, performing dynamic imaging during the aforementioned tests is paramount and can readily be carried out with ultrasound. The treatment mainly comprises footwear modifications, radiofrequency ablation, physical therapy, local (corticosteroid and anesthetic) injections into the affected webspace, and surgery. Again the use of real-time ultrasound guidance during such interventions is noteworthy. PMID- 26815265 TI - Transition from Injectable to Percutaneous Local Anesthetic Therapy in a Patient with Post-Herpetic Neuralgia. PMID- 26815266 TI - Tramadol Ultra Rapid Metabolizers at Risk for Respiratory Depression. PMID- 26815267 TI - In Response: The Cause of Fatal Respiratory Depression Is Combination of Clindamycin and Fentanyl, Rather than Tramadol. PMID- 26815268 TI - CRPS: Early Lumbar Sympathetic Block is Better Compared to Other Interventions. PMID- 26815269 TI - Focus on gastrointestinal bleeding. PMID- 26815270 TI - Resuscitation and monitoring in gastrointestinal bleeding. AB - INTRODUCTION: Gastrointestinal bleeding is a common life-threatening problem, causing significant mortality, costs and resource allocation. Its management requires a dynamic multidisciplinary approach that directs diagnostic and therapeutic priorities appropriately. MATERIALS AND METHODS: Articles published within the past 15 years, related to gastrointestinal bleeding, were reviewed through MEDLINE search, in addition to current guidelines and standards. RESULTS: Decisions of ICU admission and blood transfusion must be individualized based on the extent of bleeding, hemodynamic profile and comorbidities of the patient and the risk of rebleeding. A secure airway may be required to optimize oxygenation and to prevent aspiration. Doses of induction agents must be reduced due to the changes in volume of distribution. Volume replacement is the cornerstone of resuscitation in profuse bleeding, but nontargeted aggressive fluid resuscitation must be avoided to allow clot formation and to prevent increased bleeding. Decision to give blood transfusion must be based on physiologic triggers rather than a fixed level of hemoglobin. Coagulopathy must be corrected and hypothermia avoided. Need for massive transfusion must be recognized as early as possible, and a 1:1:1 ratio of packed red blood cells, fresh frozen plasma and platelets is recommended to prevent dilutional coagulopathy. Tromboelastography can be used to direct hemostatic resuscitation. Transfusion related lung injury (TRALI) is a significant problem with a mortality rate approaching 40%. Prevention of TRALI is important in patients with gastrointestinal bleeding, especially among patients having end-stage liver disease. Preventive strategies include prestorage leukoreduction, use of male-only or never-pregnant donors and avoidance of long storage times. Management of gastrointestinal bleeding requires delicately tailoring resuscitation to patient needs to avoid nonspecific aggressive resuscitation. "Functional hemodynamic monitoring" requires recognition of indications and limitations of hemodynamic measurements. Dynamic indices like systolic pressure variation are more reliable predictors of volume responsiveness. Noninvasive methods of hemodynamic monitoring and cardiac output measurement need further verification in patients with gastrointestinal bleeding. CONCLUSIONS: Management of gastrointestinal bleeding requires a dynamic multidisciplinary approach. The mentioned advances in management of hemorrhagic shock must be considered in resuscitation and monitoring of patients with GI bleeding. PMID- 26815271 TI - Therapeutic and interventional endoscopy for gastrointestinal bleeding. AB - INTRODUCTION: Gastrointestinal (GI) bleeding remains a common clinical problem encountered by every emergency room and trauma physician. Endoscopy remains the main approach to the diagnosis and therapy of GI bleeding. OBJECTIVES: To present the modern endoscopic approach for GI bleeding. METHODS: Narrative review based on our expertise and inclusion of classic articles dealing with interventional and therapeutic GI endoscopy. RESULTS: GI hemorrhage is now classified as upper, middle, and lower GI bleeding. Upper GI bleeding is defined as hemorrhage originating from the oropharynx to the ligament of Treitz (or papilla of Vater), middle GI bleeding occurs distal to the papilla of Vater to the terminal ileum, and lower GI bleeding is defined as bleeding distal to the ileocecal valve, including the entire colon and anorectum. Endoscopic methods used to diagnosed and treat GI bleeding include esophagogastroduodenoscopy, duodenoscopy, capsule endoscopy, double- and single-balloon enteroscopy, spiral enteroscopy, and colonosocopy. CONCLUSIONS: This is the first review paper dedicated to endoscopic therapy for bleeding involving any part of the luminal GI tract (i.e., esophagus, stomach, small bowel, and colon). Modern endoscopy permits the investigation and treatment of the majority of conditions affecting the entire hollow GI tract. PMID- 26815272 TI - Radiographic techniques for the localization and treatment of gastrointestinal bleeding of obscure origin. AB - PURPOSE/BACKGROUND: Acute gastrointestinal bleeding (GIB) is an emergency with high mortality rates, which requires a quick localization and treatment of the bleeding site. In this article, we give a summary of the diagnostic and interventional treatment of acute GIB with an emphasis on radiological methods. METHODS: The MEDLINE database identified relevant studies up until January 2011. Furthermore, experiences drawn from a highly experienced department of diagnostic radiology (~60 transarterial embolizations [TAEs]/year) were taken into account. RESULTS: Clinical risk scores are useful tools to triage patients for appropriate treatment. High-risk patients should undergo emergency endoscopy within 24 h. If endoscopical control of the bleeding cannot be achieved, a computed tomography angiography (CTA) should be done. If active bleeding (or if an active bleeding site) is found, in most cases, TAE should be performed prior to surgery because of the equal mortality rates with lower complication rates. If the site of bleeding is not identified and the patient is stable, a "watch-and-wait" strategy can be pursued. Especially for intermittent bleeding, scintigraphy with tagged red blood cells can be useful. CONCLUSION: Managing obscure acute GIB remains a challenge. The best patient care is achieved with a multidisciplinary team of endoscopists, experienced surgeons, and interventional radiologists. If emergency endoscopy fails, a CTA has to be done, which is more sensitive than conventional angiography. Based on CTA findings, a decision must be made between TAE and surgical intervention. PMID- 26815273 TI - Surgical management of lower gastrointestinal bleeding. AB - PURPOSE: Lower gastrointestinal bleeding (LGIB) is any form of bleeding distal to the Ligament of Treitz. In most cases, acute LGIB is self-limited and resolves spontaneously with conservative management. METHODS: Only a minority of approximately 10% is admitted to hospital with signs of massive bleeding and shock requiring resuscitation, urgent evaluation and treatment. RESULTS: Over the past decade, there has been a progressive decrease in upper GI events and a significant increase in lower GI events. Overall, mortality has also decreased, but in-hospital fatality due to upper or lower GI complications have remained constant. The problem is that LGIB can arise from a number of sources and may be a significant cause of hospitalisation and mortality in elderly patients. CONCLUSIONS: After initial resuscitation, the diagnosis and treatment of LGIB remains a challenge for acute care surgeons, whereby the identification of the source of bleeding is of utmost importance. PMID- 26815274 TI - Prediction of immediate and long-term benefit after kyphoplasty of painful osteoporotic vertebral fractures by preoperative MRI. AB - BACKGROUND: It is unclear if an MR-detectable bone marrow edema is a prerequisite for pain reduction and morphological correction by kyphoplasty. This comparative trial evaluates clinical and radiomorphological outcomes after kyphoplasty of painful osteoporotic vertebral fractures with and without preoperative MR detectable bone marrow edema for 1 year of follow-up. METHODS: Preoperative MR images of 45 patients who received kyphoplasty for treatment of painful osteoporotic vertebral fractures were evaluated with regard to presence (n = 27) or absence (n = 18) of vertebral bone marrow edema. Pain scores (VAS 0-100) and radiomorphological measures (midline vertebral height, kyphosis angle) were analysed at baseline, postoperatively and after 12 months. RESULTS: In the "bone edema" group, pain scores improved from 72.7 to 46.8 (postoperative) and 48.0 (12 months, P < 0.001, both). In the group without preoperative bone edema, pain score improved from 70.7 to 60.3 (postoperative, P = 0.013) and to 50.1 (12 months, P = 0.001). Pain scores of both groups were significantly different directly postoperative (P = 0.026), but not after 12 months (P = 0.714). Vertebral height restoration was slightly greater in the "bone edema" group (10.2% vs. 7.8%, P = 0.289). Correction of the kyphosis angle was greater in the "bone edema" group (P = 0.014) compared to the "no bone edema" group (P = 0.838). CONCLUSION: A preoperative MR-detectable vertebral bone marrow edema predicts a better short-term outcome after kyphoplasty, but is not a prerequisite for long term pain reduction in patients with old, chronically painful osteoporotic vertebral fractures. PMID- 26815275 TI - One-year outcome and course of recovery after severe traumatic brain injury. AB - GOAL: To describe the outcome of patients with severe traumatic brain injury (TBI) 3, 6 and 12 months after trauma. METHODS: Between January 2001 and December 2005, 13 European centres enrolled 1,172 patients with severe TBI defined as Glasgow Coma Scale (GCS) score < 9. Demographic data, trauma severity, results of computed tomography (CT) scans, data on status, treatment and outcome were recorded. The five-level Glasgow Outcome Scale (GOS) score was used to classify patients as having a "favourable" (GOS scores 5 and 4) or an "unfavourable outcome" (GOS scores 3, 2 and 1). RESULTS AND CONCLUSIONS: Of the 1,172 patients, 37% died in the intensive care unit (ICU) and 8.5% died after ICU discharge. At 12 months after trauma, almost half of the outcomes (46.6%) were classified as "favourable" (33% "good recovery", 13.6% "moderate disability") and 7.9% were classified as "unfavourable" (6.1% "severe disability", 1.8% "vegetative status"). As in previous studies, long-term outcomes were influenced by age, severity of trauma, first GCS score, pupillary status and CT findings (e.g. subdural haematoma and closed basal cistern on the first CT scan). Patients with "good recovery" had a high likelihood to remain in that category (91%). Patients with "moderate disability" had a 50% chance to improve to "good recovery". Patients with "severe disability" had a 40% chance to improve and had a 4% chance of death. Patients with "vegetative status" were more likely to die (42%) than to improve (31%). Changes were more likely to occur during the first than during the second half-year after trauma. PMID- 26815276 TI - Comparison of two different matrix-based autologous chondrocyte transplantation systems: 1 year follow-up results. AB - PURPOSE: The treatment of full-thickness cartilage defects of the knee is a common problem in orthopaedic surgery. Autologous chondrocyte transplantation (ACT) is one of the few reliable treatment options of cartilage defects with good long-term outcomes. The improvement of ACT led to the matrix-based ACT (MACT). The purpose of the study was to compare two different commercially available MACT systems. METHODS: Eleven patients with a cartilage defect of the knee were treated with the MACI((r)) system and another nine patients with the CaRes((r)) implant. The patients were prospectively followed and re-examined after one year. RESULTS: One year after surgery all but one patient have significantly improved in their clinical outcome. Both types of MACT revealed similar results in terms of increase in level of activity, pain relief and knee function. CONCLUSION: The study showed that MACT is a good therapeutic option for full-size defects of the femoral condyle. The MACI((r)) implant seems to be easier to handle which is reflected by smaller incisions and a shorter operation time. PMID- 26815277 TI - Pitfalls of lateral external fixation for supracondylar humeral fractures in children. AB - INTRODUCTION: Closed reduction and percutaneous pinning is a standard treatment for dislocated supracondylar humeral fractures in children. However, the management of these fractures remains challenging. The aim of this study was to evaluate lateral external fixation as a treatment alternative for these fractures. MATERIALS AND METHODS: All supracondylar fractures treated with lateral external fixation between 2005 and 2007 were evaluated retrospectively. Long-term outcome was assessed with regards to carrying angle, malalignment, and motion. RESULTS: Twenty-eight patients with Gartland type III fractures and one with a Y-type fracture were included in the study (mean age 6.5 years). Cosmetic results were excellent in 88%, good in 8%, and fair in one patient. Functional results were excellent in 83%, good in 10%, and fair in 7%. However, 3 patients (10%) showed complete radial palsy postoperatively. In all of these patients, high insertion of the proximal pin (2.9-3.6 cm above the fracture) was noted. On revision, one superficial lesion and one total transection of the nerve at the level of the proximal pin was detected. One patient showed no macroscopic damage. The transected nerve was reconstructed using an autograft, and all patients completely recovered within 2-6 months. CONCLUSION: Lateral external fixation is an alternative method for the treatment of displaced or unstable supracondylar fractures in children, facilitating reduction and improving fracture stability. However, iatrogenic radial nerve injury is a risk, and we therefore strongly recommend inserting the proximal pin under direct vision within 2 cm from the fracture line using a drill sleeve. PMID- 26815278 TI - School-related injuries: a retrospective 5-year evaluation. AB - PURPOSE: Children and adolescents spend up to 50% of their time at school. The purpose of this study was to assess injury patterns of school accidents (along with their treatment) in the trauma center of a German university hospital, and to compare these data to those in the literature. METHODS: All school accidents treated in a level 1 pediatric trauma center over a five-year period were statistically analyzed in a retrospective manner by chart review. RESULTS: There were 1,399 school accidents that were treated in our department. Average age of the injured person was 11.8 years, with a boy:girl ratio of 3:2. Almost 40% of the injuries occurred during school sports. The most frequently injured region was the upper extremity, including the hand (36.8%). Distortion and contusion was the most frequent diagnosis among all injuries. Sixteen percent of the cases had to be treated surgically and/or under general anesthesia, and 16% of the patients had to be admitted to the hospital. CONCLUSION: It can be concluded that special attention must be paid during school sporting activities and breaks because they account for most of the accidents. Traffic education may reduce severe injuries. Specific knowledge of the growing long bones of the upper extremity and the hand is important for the diagnosis and treatment of school accidents. PMID- 26815279 TI - Health-related quality of life of survivors of penetrating trunk trauma in Johannesburg, South Africa. AB - PURPOSE: To study how the health-related quality of life (HRQOL) of survivors of penetrating trunk trauma (PTT) changes from pre-morbid status to 6 months after hospital discharge and to determine differences in the HRQOL between subjects ventilated for short and prolonged periods of time. To determine how the HRQOL of PTT survivors compares with that of a healthy control group in order to identify limitations imposed by critical illness. METHODS: Retrospective and observational prospective assessment of the quality of life (QoL) of PTT survivors with the Medical Outcomes Short Form-36 (SF-36) UK English version questionnaire. Cross sectional assessment of the QoL of a healthy control group with the SF-36. RESULTS: The physical component summary (PCS) score was significantly reduced for the short mechanical ventilation (MV) group (n = 13) at 1 and 3 months compared to pre-admission status (p = 0.00, respectively). The mental component summary (MCS) score was significantly reduced at 1, 3 and 6 months (p = 0.00, respectively). The PCS and MCS were significantly reduced for the long MV group (n = 29) at all three assessments compared to the pre-admission HRQOL (p = 0.00 0.01). The short MV group reported HRQOL comparable to that of the healthy group (n = 40) at 6 months after discharge. The long MV group had a significant reduction in the PCS at 1, 3 and 6 months compared to the healthy group (p = 0.00, respectively). The long MV group had significantly reduced PCS at 3 and 6 months compared to the short MV group (p = 0.01 and 0.00, respectively). CONCLUSIONS: Subjects who had higher morbidity and prolonged MV suffered from reduced HRQOL related to physical health for up to 6 months after discharge. PMID- 26815280 TI - Current Practice vs. Guideline Based Imaging in Abdominal Radiology in the German Speaking Area: Results of an Online Survey. AB - PURPOSE: The working group for abdominal imaging within the German Roentgen Society (DRG) performed an online survey amongst radiologist concerning the current status of techniques for abdominal imaging. The results of this survey were compared with the most recent guidelines. MATERIALS AND METHODS: We performed an online survey open for all members of the DRG during a 76-day period with 65 questions and an overall estimated time for finishing the questionnaire of 15 minutes concerning technical specifications for abdominal radiological imaging. The results were evaluated using descriptive statistics. RESULTS: 90 of all participants, who filled out the survey covering more than 80% of the questions, were included in the statistical evaluation. 27% of all participants were registered radiologists while 73% represented radiologists working in a hospital. Most participants worked in a managerial position. The participants gave detailed information regarding the radiological techniques used in dedicated organ systems (esophagus, stomach, pancreas, liver, small intestines, colon) regarding acquired contrast phases and oral and intravenous administration of contrast medium. CONCLUSION: The results confirm that most radiologists participating in this survey perform their examinations and choose their modalities in conformity with the current existing clinical guidelines. Because most clinical guidelines do not specify radiological examinations in detail, there is a noteworthy heterogeneity of the acquired contrast phases and major divergence in terms of technical parameters. Therefore a joint radiological effort should be initiated for developing and publishing updated radiological parameters for abdominal imaging. KEY POINTS: * In German speaking countries indications for abdominal radiological examinations are performed with a high compliance to published guidelines. * There is a significant heterogeneity regarding the acquisition of different contrast phases for parenchymal abdominal organs. * There is an urgent need to publish radiological recommendations and guidelines based on current radiological literature for radiological abdominal imaging. PMID- 26815281 TI - Interobserver Variability in the Differential Diagnosis of Benign Bone Tumors and Tumor-like Lesions. AB - PURPOSE: The interobserver-variability of radiological diagnosis of benign bone tumors (BBT) and tumor-like lesions (TLL) was examined in order to identify difficult-to-diagnose entities, to examine the frequency of advanced diagnostics and to describe the number of interdisciplinary tumor center diagnoses (IDT) in comparison with diagnoses upon referral (ED) and radiologists' diagnoses (RD). MATERIALS AND METHODS: We retrospectively reviewed 413 patients with 272 BBT and 141 TLL, classified either histologically or through interdisciplinary consultation. Discrepancies between groups were analyzed and rates of additional imaging and biopsy to establish diagnosis were assessed. RESULTS: In BBT the number of identical radiological diagnoses was 56 (ED) and 81 % (RD) compared to the IDT, while in the latter additional imaging were obtained in 30 % cases. In 21 % (12 % to establish diagnosis) BBT were biopsied, the ED matching the histology 40 %, the RD 60 % and the IDT 76 % of the time. For TLL diagnosed through radiology, ED and RD matched IDT 31 % and 61 % of the time, with additional imaging being obtained in 21 % of cases (IDT). In 36 % (27 % to establish diagnosis) biopsy was performed, with histological diagnosis matching the IDT, RD and ED in 51, 27 and 20 %. Diagnostic challenges were apparent in enchondromas, non-ossifying fibromas (NOF), solitary (SBC) and aneurysmal bone cysts (ABC). Ganglia can be misinterpreted as a tumor. CONCLUSIONS: Establishing a definitive diagnosis for BBT and TLL can be challenging with the latter posing greater difficulties. An interdisciplinary approach involving radiologists, orthopedics and pathologists was found to improve diagnostic accuracy. KEY POINTS: * Benign bone tumors (BBT) and tumor-like lesions (TLL) present a diagnostic challenge, while enchondroma, NOF, SBC and ABC were difficult to diagnose, and ganglia can be misinterpreted as a tumor* Additional imaging studies were required for diagnosis in 29 % and 21 % of cases for BBT and TLL, respectively, biopsies in 12 % of cases for BBT and 27 % for TLL* Sound diagnoses can be made through interdisciplinary case discussion, while reducing the risk of overtreatment Citation Format: * Scheitza P, Uhl M, Hauschild O et al. Interobserver Variability in the Differential Diagnosis of Benign Bone Tumors and Tumor-like Lesions. Fortschr Rontgenstr 2016; 188: 479 - 487. PMID- 26815282 TI - Improving Radiation Awareness and Feeling of Personal Security of Non Radiological Medical Staff by Implementing a Traffic Light System in Computed Tomography. AB - PURPOSE: Non-radiological medical professionals often need to remain in the scanning room during computed tomography (CT) examinations to supervise patients in critical condition. Independent of protective devices, their position significantly influences the radiation dose they receive. The purpose of this study was to assess if a traffic light system indicating areas of different radiation exposure improves non-radiological medical staff's radiation awareness and feeling of personal security. MATERIAL AND METHODS: Phantom measurements were performed to define areas of different dose rates and colored stickers were applied on the floor according to a traffic light system: green = lowest, orange = intermediate, and red = highest possible radiation exposure. Non-radiological medical professionals with different years of working experience evaluated the system using a structured questionnaire. Kruskal-Wallis and Spearman's correlation test were applied for statistical analysis. RESULTS: Fifty-six subjects (30 physicians, 26 nursing staff) took part in this prospective study. Overall rating of the system was very good, and almost all professionals tried to stand in the green stickers during the scan. The system significantly increased radiation awareness and feeling of personal protection particularly in staff with <= 5 years of working experience (p < 0.05). The majority of non-radiological medical professionals stated that staying in the green stickers and patient care would be compatible. Knowledge of radiation protection was poor in all groups, especially among entry-level employees (p < 0.05). CONCLUSION: A traffic light system in the CT scanning room indicating areas with lowest, intermediate, and highest possible radiation exposure is much appreciated. It increases radiation awareness, improves the sense of personal radiation protection, and may support endeavors to lower occupational radiation exposure, although the best radiation protection always is to re-main outside the CT room during the scan. KEY POINTS: * A traffic light system indicating areas with different radiation exposure within the computed tomography scanner room is much appreciated by non radiological medical staff. * The traffic light system increases non-radiological medical staff's radiation awareness and feeling of personal protection. * Knowledge on radiation protection was poor in non-radiological medical staff, especially in those with few working experience. PMID- 26815283 TI - Whole-Body Diffusion Imaging Applying Simultaneous Multi-Slice Excitation. AB - PURPOSE: The purpose of this study was to examine the feasibility of a fast protocol for whole-body diffusion-weighted imaging (WB-DWI) using a slice accelerated echo-planar sequence, which, when using comparable image acquisition parameters, noticeably reduces measurement time compared to a conventional WB-DWI protocol. MATERIALS AND METHODS: A single-shot echo-planar imaging sequence capable of simultaneous slice excitation and acquisition was optimized for WB-DWI on a 3 T MR scanner, with a comparable conventional WB-DWI protocol serving as the reference standard. Eight healthy individuals and one oncologic patient underwent WB-DWI. Quantitative analysis was carried out by measuring the apparent diffusion coefficient (ADC) and its coefficient of variation (CV) in different organs. Image quality was assessed qualitatively by two independent radiologists using a 4-point Likert scale. RESULTS: Using our proposed protocol, the scan time of the WB-DWI measurement was reduced by up to 25.9 %. Both protocols, the slice accelerated protocol and the conventional protocol, showed comparable image quality without statistically significant differences in the reader scores. Similarly, no significant differences of the ADC values of parenchymal organs were found, whereas ADC values of brain tissue were slightly higher in the slice accelerated protocol. CONCLUSION: It was demonstrated that slice-accelerated DWI can be applied to WB-DWI protocols with the potential to greatly reduce the required measurement time, thereby substantially increasing clinical applicability. KEY POINTS: *Whole-body diffusion-weighted imaging (WB-DWI) using simultaneous multi-slice and blipped-CAIPIRINHA reduces the measurement time strongly without having a significant impact on image quality. *The reduction in measurement time might strongly contribute to the clinical applicability of WB DWI. *However, further refinement of the slice-accelerated EPI sequence, and the WB-DWI protocol applying this sequence type seems necessary; and the value of such WB-DWI protocols for assessment of systemic oncological diseases needs to be investigated in further clinical studies. PMID- 26815284 TI - [Not Available]. PMID- 26815285 TI - Noxs on tumour's door: oxidative stress drives tumour vascularization. PMID- 26815286 TI - Development and First Validation of a Disease Activity Score for Gout. AB - OBJECTIVE: To develop a new composite disease activity score for gout and provide its first validation. METHODS: Disease activity has been defined as the ongoing presence of urate deposits that lead to acute arthritis and joint damage. Every measure for each Outcome Measures in Rheumatology core domain was considered. A 3 step approach (factor analysis, linear discriminant analysis, and linear regression) was applied to derive the Gout Activity Score (GAS). Decision to change treatment or 6-month flare count were used as the surrogate criteria of high disease activity. Baseline and 12-month followup data of 446 patients included in the Kick-Off of the Italian Network for Gout cohort were used. Construct- and criterion-related validity were tested. External validation on an independent sample is reported. RESULTS: Factor analysis identified 5 factors: patient-reported outcomes, joint examination, flares, tophi, and serum uric acid (sUA). Discriminant function analysis resulted in a correct classification of 79%. Linear regression analysis identified a first candidate GAS including 12 month flare count, sUA, visual analog scale (VAS) of pain, VAS global activity assessment, swollen and tender joint counts, and a cumulative measure of tophi. Alternative scores were also developed. The developed GAS demonstrated a good correlation with functional disability (criterion validity) and discrimination between patient- and physician-reported measures of active disease (construct validity). The results were reproduced in the external sample. CONCLUSION: This study developed and validated a composite measure of disease activity in gout. Further testing is required to confirm its generalizability, responsiveness, and usefulness in assisting with clinical decisions. PMID- 26815287 TI - Distinct Functions of Autoantibodies Against Interferon in Systemic Lupus Erythematosus: A Comprehensive Analysis of Anticytokine Autoantibodies in Common Rheumatic Diseases. AB - OBJECTIVE: Anticytokine autoantibodies occur across a range of hematologic, pulmonary, and infectious diseases. However, systematic investigation of their presence and significance in autoimmune diseases is lacking. This study was undertaken to examine the distinct functions of anticytokine autoantibodies in patients with systemic lupus erythematosus (SLE) compared to patients with other rheumatic diseases and healthy controls. METHODS: Serum samples from patients with SLE (n = 199), patients with primary Sjogren's syndrome (SS) (n = 150), patients with rheumatoid arthritis (RA) (n = 149), and healthy controls (n = 200) were screened for 24 anticytokine autoantibodies using a multiplex bead-based assay. To evaluate the biologic activity of anticytokine autoantibodies, their ability to block cytokine-induced signal transduction or protein expression was measured. RNA sequencing was performed on whole blood in a subset of healthy controls and patients with SLE. RESULTS: Patients with SLE and those with SS had a striking excess of autoantibodies against interferons and the interferon responsive chemokine interferon-inducible protein 10 (IP-10). Only autoantibodies against type I interferon, interleukin-12 (IL-12), and IL-22 exhibited neutralizing activity. In SLE, the presence of anti-interferon-gamma autoantibodies was correlated with more severe disease activity, higher levels of anti-double-stranded DNA antibodies, and elevated expression of interferon alpha/beta-inducible genes. Conversely, in SLE patients with blocking anti interferon-alpha autoantibodies, the type I interferon gene expression signature was normalized. Anti-type III interferon autoantibodies (lambda2, lambda3) and anti-IP-10 autoantibodies were newly recognized in SLE patient serum, and autoantibodies against macrophage-colony stimulating factor, IL-4, IL-7, IL-17, and IL-22, none of which have been previously identified in rheumatic conditions, were discovered. CONCLUSION: Anticytokine autoantibodies are associated with distinct patterns of disease in SLE, SS, and RA. Anti-interferon autoantibodies are overrepresented in patients with SLE and those with SS, and fall into distinct functional classes, with only a subset of anti-type I interferon antibodies exhibiting neutralizing activity. Anti-interferon-gamma autoantibodies are correlated with increased disease activity and interferon-related gene expression, suggesting that such autoantibodies may contribute to the pathogenesis of SLE. PMID- 26815288 TI - Potential Biomarker Peptides Associated with Acute Alcohol-Induced Reduction of Blood Pressure. AB - The purpose of this study was to explore the peptides that are related to acute reduction of blood pressure after alcohol drinking. Venous blood was collected from male healthy volunteers before and after drinking white wine (3 ml/kg weight) containing 13% of ethanol. Peptidome analysis for serum samples was performed using a new target plate, BLOTCHIP(r). Alcohol caused significant decreases in systolic and diastolic blood pressure levels at 45 min. The peptidome analysis showed that the levels of three peptides of m/z 1467, 2380 and 2662 changed significantly after drinking. The m/z 1467 and 2662 peptides were identified to be fragments of fibrinogen alpha chain, and the m/z 2380 peptide was identified to be a fragment of complement C4. The intensities of the m/z 2380 and m/z 1467 peptides before drinking were associated with % decreases in systolic and diastolic blood pressure levels at 45 min after drinking compared with the levels before drinking, while there were no significant correlations between the intensity of the m/z 2662 peptide and % decreases in systolic and diastolic blood pressure levels after drinking. The m/z 1467 and 2380 peptides are suggested to be markers for acute reduction of blood pressure after drinking alcohol. PMID- 26815289 TI - Polar solvent effects on tartaric acid binding by aromatic oligoamide foldamer capsules. AB - Aromatic oligoamide sequences able to fold into single helical capsules were functionalized with two types of side chains to make them soluble in various solvents such as chloroform, methanol or water and their propensity to recognize tartaric acid was evaluated. The binding affinities to tartaric acid and binding thermodynamics in different media were investigated by variable temperature (1)H NMR and ITC experiments, the two methods giving consistent results. We show that tartaric acid binding mainly rests on enthalpically favourable polar interactions that were found to be sufficiently strong to be effective in the presence of a polar aprotic solvent (DMSO) and even in pure methanol. Binding in water was very weak. The stronger binding interactions were found to be more susceptible to the effect of competitive solvents and compensated by unfavourable entropic effects. Thus, the best host in a less polar medium eventually was found to be the worst host in protic solvents. An interesting case of entropically driven binding was evidenced in methanol. PMID- 26815290 TI - Naloxone injections into CA3 disrupt pattern completion associated with relapse from cocaine seeking. AB - The goal of the present research was to assess the degree to which a pattern completion process operates in cue-induced relapse to cocaine-seeking behavior. Using a novel cue-preference version of the place preference task, rats were administered cocaine or saline, which resulted in a preference for the cocaine paired cues. After 21 days of abstinence and prior to the preference test, for one group, PBS or naloxone was injected into the CA3 subregion of the hippocampus and for a second group, saline or naloxone was injected systemically. The results indicated that infusions of naloxone into CA3 or systemic injections produced a marked disruption for one and two cues, but had minimal disruptive effect for three or four cues, suggesting that naloxone injections disrupt CA3 function and trigger a deficit in a pattern completion process. Thus, it appears that cue based activation of the dorsal CA3 might be a critical trigger via a pattern completion process. Based on additional analyses it appears that there is a disruption primarily for object touches for one cue naloxone injections into the CA3 or systemic injections, but no effect on time (spatial context). (c) 2016 Wiley Periodicals, Inc. PMID- 26815292 TI - Influence of atmospheric stability and transport on CH4 concentrations in northern Spain. AB - Continuous methane (CH4) concentrations were measured in Northern Spain over two years (2011-2012) by multi-point sampling at 1.8, 3.7 and 8.3m using a Picarro analyser. The technique is based on cavity ring-down spectroscopy. The contrast in mean concentrations was about 1.2ppb, with 95th percentiles differing by 2.2ppb and mean minimum concentrations proving similar. Temporal variations of CH4 were also analysed, with a similar seasonal variability being found for the three heights. The highest CH4 concentrations were obtained in late autumn and winter and the lowest in summer, yielding a range of 52ppb. This variation may depend on the active photochemical reaction with OH radical during a period of intense solar radiation and changes in soil conditions together with variations in emissions. Peak concentration levels were recorded at night-time, between 5:00 7:00 GMT, with mean values ranging between 1920 and 1923ppb. The lowest value, around 1884ppb, was obtained at 16:00 GMT. This diurnal variation was mainly related to vertical mixing and photochemistry. Therefore, CH4 concentrations were also examined using the bulk Richardson number (RB) as a stability indicator. Four groups were distinguished: unstable cases, situations with pure shear flow, transitional stages and drainage flows. The highest contrast in mean CH4 concentrations between lower and upper heights was obtained for the transition and drainage cases, mainly associated to high concentrations from nearby sources. The impact of long range transport was analysed by means of 3-day isobaric backward air mass trajectories, which were calculated taking into account origins from Europe, Africa, the Atlantic Ocean and Local conditions. Assessment of the results showed the influence of S and SE wind sectors, especially with Local conditions associated with low winds. Finally, an estimation of the background CH4 concentration in the study period provided an average value of about 1892ppb. PMID- 26815291 TI - Thrombolysis with Low-Dose Tissue Plasminogen Activator 3-4.5 h After Acute Ischemic Stroke in Five Hospital Groups in Japan. AB - Clinical data from Japan on the safety and real-world outcomes of alteplase (tPA) thrombolysis in the extended therapeutic window are lacking. The aim of this study was to assess the safety and real-world outcomes of tPA administered within 3-4.5 h of stroke onset. The study comprised consecutive acute ischemic stroke patients (n = 177) admitted across five hospitals between September 2012 and August 2014. Patients received intravenous tPA within <3 or 3-4.5 h of stroke onset. Endovascular therapy was used for tPA-refractory patients. In the 3-4.5 h subgroup (31.6 % of patients), tPA was started 85 min later than the <3 h group (220 vs. 135 min, respectively). However, outcome measures were not significantly different between the <3 and 3-4.5 h subgroups for recanalization rate (67.8 vs. 57.1 %), symptomatic intracerebral hemorrhage (2.5 vs. 3.6 %), modified Rankin Scale score of 0-1 at 3 months (36.0 vs. 23.4 %), and mortality (6.9 vs. 8.3 %). We present data from 2005 to 2012 using a therapeutic window <3 h showing comparable results. tPA following endovascular therapy with recanalization might be superior to tPA only with recanalization (81.0 vs. 59.1 %). Compared with administration within 3 h of ischemic stroke onset, tPA administration within 3 4.5 h of ischemic stroke onset in real-world stroke emergency settings at multiple sites in Japan is as safe and has the same outcomes. PMID- 26815294 TI - Seasonal variations in fate and removal of trace organic chemical contaminants while operating a full-scale membrane bioreactor. AB - Trace organic chemical (TrOC) contaminants are of concern for finished water from water recycling schemes because of their potential adverse environmental and public health effects. Understanding the impacts of seasonal variations on fate and removal of TrOCs is important for proper operation, risk assessment and management of treatment systems for water recycling such as membrane bioreactors (MBRs). Accordingly, this study investigated the fate and removal of a wide range of TrOCs through a full-scale MBR plant during summer and winter seasons. TrOCs included 12 steroidal hormones, 3 xeno-estrogens, 2 pesticides and 23 pharmaceuticals and personal care products. Seasonal differences in the mechanisms responsible for removing some of the TrOCs were evident. In particular the contribution of biotransformation and biomass adsorption to the overall removal of estrone, bisphenol A, 17beta-estradiol and triclosan were consistently different between the two seasons. Substantially higher percentage removal via biotransformation was observed during the summer sampling period, which compensated for a reduction in removal attributed to biomass adsorption. The opposite was observed during winter, where the contribution of biotransformation to the overall removal of these TrOCs had decreased, which was offset by an improvement in biomass adsorption. The exact mechanisms responsible for this shift are unknown, however are likely to be temperature related as warmer temperatures can lower sorption efficiency, yet enhance biotransformation of these TrOCs. PMID- 26815293 TI - An index for estimating the potential metal pollution contribution to atmospheric particulate matter from road dust in Beijing. AB - The resuspension of road dust from street surfaces could be a big contributor to atmospheric particulate pollution in the rapid urbanization context in the world. However, to date what its potential contribution to the spatial pattern is little known. Here we developed an innovative index model called the road dust index (RI<105MUm) and it combines source and transport factors for road dust particles <105MUm in diameter. It could quantify and differentiate the impact of the spatial distribution of the potential risks posed by metals associated with road dust on atmospheric suspended particles. The factors were ranked and weighted based on road dust characteristics (the amounts, grain sizes, and mobilities of the road dust, and the concentrations and toxicities of metals in the road dust). We then applied the RI<105MUm in the Beijing region to assess the spatial distribution of the potential risks posed by metals associated with road dust on atmospheric suspended particles. The results demonstrated that the road dust in urban areas has higher potential risk of metal to atmospheric particles than that in rural areas. The RI<105MUm method offers a new and useful tool for assessing the potential risks posed by metals associated with road dust on atmospheric suspended particles and for controlling atmospheric particulate pollution caused by road dust emissions. PMID- 26815295 TI - Reduction of antibiotic resistance genes in municipal wastewater effluent by advanced oxidation processes. AB - This study investigated the reduction of antibiotic resistance genes (ARGs), intI1 and 16S rRNA genes, by advanced oxidation processes (AOPs), namely Fenton oxidation (Fe(2+)/H2O2) and UV/H2O2 process. The ARGs include sul1, tetX, and tetG from municipal wastewater effluent. The results indicated that the Fenton oxidation and UV/H2O2 process could reduce selected ARGs effectively. Oxidation by the Fenton process was slightly better than that of the UV/H2O2 method. Particularly, for the Fenton oxidation, under the optimal condition wherein Fe(2+)/H2O2 had a molar ratio of 0.1 and a H2O2 concentration of 0.01molL(-1) with a pH of 3.0 and reaction time of 2h, 2.58-3.79 logs of target genes were removed. Under the initial effluent pH condition (pH=7.0), the removal was 2.26 3.35 logs. For the UV/H2O2 process, when the pH was 3.5 with a H2O2 concentration of 0.01molL(-1) accompanied by 30min of UV irradiation, all ARGs could achieve a reduction of 2.8-3.5 logs, and 1.55-2.32 logs at a pH of 7.0. The Fenton oxidation and UV/H2O2 process followed the first-order reaction kinetic model. The removal of target genes was affected by many parameters, including initial Fe(2+)/H2O2 molar ratios, H2O2 concentration, solution pH, and reaction time. Among these factors, reagent concentrations and pH values are the most important factors during AOPs. PMID- 26815296 TI - How rural land use management facilitates drought risk adaptation in a changing climate - A case study in arid northern China. AB - Under a warming climate, frequent drought and water scarcity in northern China have severely disrupted agricultural production and posed a substantial threat to farmers' livelihoods. Based on first-hand data collected through in-depth interviews with local managers and farmer households, this study evaluated the effectiveness of rural land use management in mitigating drought risk, ensuring food security and improving farmers' livelihoods. Our findings indicate that a) reforestation on low-yield cropland not only can improve the eco-environment but can also prominently mitigate the production risk to local farmers; b) replacing the traditional border irrigation with sprinkler irrigation has substantially curbed agricultural water usage and increased the per unit of output; and c) in recent years, instead of planting water-intensive grain crops, local farmers cultivated more forage crops to raise animals, which greatly diversified their income sources and reduced the drought risk of agricultural production. By performing an empirical case study in drought-prone Inner Mongolia, this study provides decision-makers with insights into how to strategically adapt to drought risk and reduce rural poverty within the broader context of climate change. PMID- 26815297 TI - Diffusion related isotopic fractionation effects with one-dimensional advective dispersive transport. AB - Aqueous phase diffusion-related isotope fractionation (DRIF) for carbon isotopes was investigated for common groundwater contaminants in systems in which transport could be considered to be one-dimensional. This paper focuses not only on theoretically observable DRIF effects in these systems but introduces the important concept of constraining "observable" DRIF based on constraints imposed by the scale of measurements in the field, and on standard limits of detection and analytical uncertainty. Specifically, constraints for the detection of DRIF were determined in terms of the diffusive fractionation factor, the initial concentration of contaminants (C0), the method detection limit (MDL) for isotopic analysis, the transport time, and the ratio of the longitudinal mechanical dispersion coefficient to effective molecular diffusion coefficient (Dmech/Deff). The results allow a determination of field conditions under which DRIF may be an important factor in the use of stable carbon isotope measurements for evaluation of contaminant transport and transformation for one-dimensional advective dispersive transport. This study demonstrates that for diffusion-dominated transport of BTEX, MTBE, and chlorinated ethenes, DRIF effects are only detectable for the smaller molar mass compounds such as vinyl chloride for C0/MDL ratios of 50 or higher. Much larger C0/MDL ratios, corresponding to higher source concentrations or lower detection limits, are necessary for DRIF to be detectable for the higher molar mass compounds. The distance over which DRIF is observable for VC is small (less than 1m) for a relatively young diffusive plume (<100years), and DRIF will not easily be detected by using the conventional sampling approach with "typical" well spacing (at least several meters). With contaminant transport by advection, mechanical dispersion, and molecular diffusion this study suggests that in field sites where Dmech/Deff is larger than 10, DRIF effects will likely not be observable for common groundwater contaminants. Importantly, under most field conditions, Dmech/Deff>=10 is usually satisfied in the longitudinal direction, suggesting that DRIF is not likely to be observable in most groundwater systems in which contaminant transport is predominantly one-dimensional. Given the importance in the MDL it is recommended that MDL should always be explicitly reported in both modeling and field studies. PMID- 26815298 TI - Photodegradation of estrogenic endocrine disrupting steroidal hormones in aqueous systems: Progress and future challenges. AB - This article reviews different photodegradation technologies used for the removal of four endocrine disrupting chemicals (EDCs): estrone (E1), 17beta-estradiol (E2), estriol (E3) and 17alpha-ethinylestradiol (EE2). The degradation efficiency is greater under UV than visible light; and increases with light intensity up to when mass transfer becomes the rate limiting step. Substantial rates are observed in the environmentally relevant range of pH7-8, though higher rates are obtained for pH above the pKa (~10.4) of the EDCs. The effects of dissolved organic matter (DOM) on EDC photodegradation are complex with both positive and negative impacts being reported. TiO2 remains the best catalyst due to its superior activity, chemical and photo stability, cheap commercial availability, capacity to function at ambient conditions and low toxicity. The optimum TiO2 loading is 0.05-1gl(-1), while higher loadings have negative impact on EDC removal. The suspended catalysts prove to be more efficient in photocatalysis compared to the immobilised catalysts, while the latter are considered more suitable for commercial scale applications. Photodegradation mostly follows 1st or pseudo 1st order kinetics. Photodegradation typically eradicates or moderates estrogenic activity, though some intermediates are found to exhibit higher estrogenicity than the parent EDCs; the persistence of estrogenic activity is mainly attributed to the presence of the phenolic moiety in intermediates. PMID- 26815299 TI - Role of a productive lake in carbon sequestration within a calcareous catchment. AB - For a long time, lakes were considered unimportant in the global carbon (C) cycle because of their small total area compared to the ocean. Over the last two decades, a number of studies have highlighted the important role of lakes in both sequestering atmospheric C and modifying the C flux from the catchment by degassing CO2 and methane and burying calcite and organic matter in the sediment. Based on a full C mass balance, high frequency measurements of lake metabolism and stable isotope analysis of a large shallow eutrophic lake in Estonia, we assess the role alkaline lakes play in augmenting the strength of terrestrial carbonate weathering as a temporary CO2 sink. We show that a large part of organic C buried in the sediments in this type of lakes originates from the catchment although a direct uptake from the atmosphere during periods of intensive phytoplankton growth in eutrophic conditions contributes to the carbon sink. PMID- 26815300 TI - Electrophoretic Mobility of a Dilute, Highly Charged "Soft" Spherical Particle in a Charged Hydrogel. AB - In this paper, numerical modeling studies are carried out on the electrophoretic mobility of a dilute, highly charged "soft" spherical particle in a hard hydrogel subjected to a weak, constant, external electric field. The particle contains a solid core with either a uniform charge density or "zeta" potential on its surface. Outside of this lies a charged gel layer of uniform thickness, composition, and charge density. The present work extends previous studies by accounting for the "relaxation effect", or distortion of the charge distribution in the vicinity of the model particle due to the imposition of an external electric and/or flow field. The particle gel layer and ambient hydrogel are modeled as porous Brinkman media. The (steady state) electrodynamic problem is solved at the level of the Poisson equation. Applications emphasize the influence of the relaxation effect and hydrogel charge density on the electrophoretic mobility. PMID- 26815301 TI - Much to learn about teaching: Reconciling form, function, phylogeny, and development. AB - The collection of commentaries expands an already extensive field of research on teaching, and contributes new questions, techniques, and strengths to the evolutionary approach proposed in the target article. In my response, I show how reconciling multiple levels of explanation - mechanistic, ontogenetic, phylogenetic, and functional - enables researchers to build a more integrated, interdisciplinary approach to the study of teaching in humans and other animals. PMID- 26815302 TI - Comparison of Chemical Sensitivity of Fresh and Long-Stored Heat Resistant Neosartorya fischeri Environmental Isolates Using BIOLOG Phenotype MicroArray System. AB - Spoilage of heat processed food and beverage by heat resistant fungi (HRF) is a major problem for food industry in many countries. Neosartorya fischeri is the leading source of spoilage in thermally processed products. Its resistance to heat processing and toxigenicity makes studies about Neosartorya fischeri metabolism and chemical sensitivity essential. In this study chemical sensitivity of two environmental Neosartorya fischeri isolates were compared. One was isolated from canned apples in 1923 (DSM3700), the other from thermal processed strawberry product in 2012 (KC179765), used as long-stored and fresh isolate, respectively. The study was conducted using Biolog Phenotype MicroArray platforms of chemical sensitivity panel and traditional hole-plate method. The study allowed for obtaining data about Neosartorya fischeri growth inhibitors. The fresh isolate appeared to be much more resistant to chemical agents than the long stored isolate. Based on phenotype microarray assay nitrogen compounds, toxic cations and membrane function compounds were the most effective in growth inhibition of N. fischeri isolates. According to the study zaragozic acid A, thallium(I) acetate and sodium selenate were potent and promising N. fischeri oriented fungicides which was confirmed by both chemical sensitivity microplates panel and traditional hole-plate methods. PMID- 26815303 TI - Periodontal treatment and glycaemic control in patients with diabetes and periodontitis: an umbrella review. AB - BACKGROUND: Studies suggest that non-surgical periodontal treatment improves glycaemic control in patients with diabetes and periodontitis. The aim of this umbrella review is to summarize the effects of periodontal treatment on glycaemic control in patients with periodontitis and diabetes. METHODS: A systematic review of systematic reviews with or without meta-analysis published between 1995 and 2015 was performed. Three independent reviewers assessed for article selection, quality and data extraction. RESULTS: Thirteen (13) systematic reviews/meta analysis were included for qualitative synthesis. A reduction (0.23 to 1.03 percentage points) in the levels of HbA1c at 3 months after periodontal intervention was found. This reduction was statistically significant in 10/12 meta-analysis. One review with sufficiently large samples found a non-significant reduction (-0.014 percentage points; 95% CI -0.18 to 0.16; p = 0.87). Only three studies separated the use of adjunctive antibiotics and found a reduction of 0.36 percentage points but the difference was not statistically significant. CONCLUSIONS: Highly heterogeneous short-term studies with small sample size suggest that periodontal treatment could help improve glycaemic control at 3 months in patients with type 2 diabetes and periodontitis. However, longer term studies having sufficient sample size do not provide evidence that periodontal therapy improves glycaemic control in these patients. PMID- 26815304 TI - Patient Preferences for Information on Post-Acute Care Services. AB - The purpose of the current study was to explore what hospitalized patients would like to know about post-acute care (PAC) services to ultimately help them make an informed decision when offered PAC options. Thirty hospitalized adults 55 and older in a Northeastern U.S. academic medical center participated in a qualitative descriptive study with conventional content analysis as the analytical technique. Three themes emerged: (a) receiving practical information about the services, (b) understanding "how it relates to me," and (c) having opportunities to understand PAC options. Study findings inform clinicians what information should be included when discussing PAC options with older adults. Improving the quality of discharge planning discussions may better inform patient decision making and, as a result, increase the numbers of patients who accept a plan of care that supports recovery, meets their needs, and results in improved quality of life and fewer readmissions. [Res Gerontol Nurs. 2016; 9(4):175-182.]. PMID- 26815305 TI - Increased cell survival of cells exposed to superparamagnetic iron oxide nanoparticles through biomaterial substrate-induced autophagy. AB - The cellular uptake of nanoparticles (NPs) can be promoted by NP surface modification but cell viability is often sacrificed. Our previous study has shown that intracellular uptake of iron oxide NPs was significantly increased for cells cultured on chitosan. However, the mechanism for having the higher cellular uptake as well as better cell survival on the chitosan surface remains unclear. In this study, we sought to clarify if the autophagic response may contribute to cell survival under excessive NP exposure conditions on chitosan. L929 fibroblasts and neural stem cells (NSCs) were challenged with different concentrations (0-300 MUg ml(-1)) of superparamagnetic iron oxide NPs. The autophagic response as well as the metabolic activity of cells was evaluated. Results showed that culturing both types of cells on chitosan substrates significantly enhanced the cellular uptake of NPs. At higher NP concentrations, cells on chitosan showed a greater survival rate than those on TCPS. The expression levels of autophagy-related genes (Atg5 and Atg7 genes) and autophagy associated protein (LC3-II) on chitosan were higher than that on TCPS. The NP exposure further increased the expressions. We suggest that cells cultured on chitosan were more tolerant to NP cytotoxicity because of the increased autophagic response. Moreover, NP exposure increased the metabolic activity of cells grown on chitosan, while it decreased the metabolism of cells cultured on TCPS. In animal studies, iron oxide-labeled NSCs were injected in zebrafish embryos. Results also showed that cells grown on chitosan had better survival after transplantation than those grown on TCPS. Taken together, chitosan as a culture substrate can induce cell autophagy to increase cell survival in particular for NP-labeled cells. This will be valuable for the biomedical application of NPs in cell therapy. PMID- 26815306 TI - Protein Z: A putative novel biomarker for early detection of ovarian cancer. AB - Ovarian cancer (OC) has the highest mortality of all gynaecological cancers. Early diagnosis offers an approach to achieving better outcomes. We conducted a blinded-evaluation of prospectively collected preclinical serum from participants in the multimodal group of the United Kingdom Collaborative Trial of Ovarian Cancer Screening. Using isobaric tags (iTRAQ) we identified 90 proteins differentially expressed between OC cases and controls. A second targeted mass spectrometry analysis of twenty of these candidates identified Protein Z as a potential early detection biomarker for OC. This was further validated by ELISA analysis in 482 serial serum samples, from 80 individuals, 49 OC cases and 31 controls, spanning up to 7 years prior to diagnosis. Protein Z was significantly down-regulated up to 2 years pre-diagnosis (p = 0.000000411) in 8 of 19 Type I patients whilst in 5 Type II individuals, it was significantly up-regulated up to 4 years before diagnosis (p = 0.01). ROC curve analysis for CA-125 and CA-125 combined with Protein Z showed a statistically significant (p = 0.00033) increase in the AUC from 77 to 81% for Type I and a statistically significant (p= 0.00003) increase in the AUC from 76 to 82% for Type II. Protein Z is a novel independent early detection biomarker for Type I and Type II ovarian cancer; which can discriminate between both types. Protein Z also adds to CA-125 and potentially the Risk of Ovarian Cancer algorithm in the detection of both subtypes. PMID- 26815307 TI - Facet-Dependent Cr(VI) Adsorption of Hematite Nanocrystals. AB - In this study, the adsorption process of Cr(VI) on the hematite facets was systematically investigated with synchrotron-based Cr K-edge extended X-ray absorption fine structure (EXAFS) spectroscopy, in situ attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, density functional theory calculation, and surface complexation models. Structural model fitting of EXAFS spectroscopy suggested that the interatomic distances of Cr-Fe were, respectively, 3.61 A for the chromate coordinated hematite nanoplates with exposed {001} facets, 3.60 and 3.30 A for the chromate coordinated hematite nanorods with exposed {001} and {110} facets, which were characteristic of inner sphere complexation. In situ ATR-FTIR spectroscopy analysis confirmed the presence of two inner-sphere surface complexes with C3nu and C2nu symmetry, while the C3nu and C2nu species were assigned to monodentate and bidentate inner-sphere surface complexes with average Cr-Fe interatomic distances of 3.60 and 3.30 A, respectively. On the basis of these experimental and theoretical results, we concluded that HCrO4(-) as dominated Cr(VI) species was adsorbed on {001} and {110} facets in inner-sphere monodentate mononuclear and bidentate binuclear configurations, respectively. Moreover, the Cr(VI) adsorption performance of hematite facets was strongly dependent on the chromate complexes formed on the hematite facets. PMID- 26815308 TI - Ras Conformational Ensembles, Allostery, and Signaling. AB - Ras proteins are classical members of small GTPases that function as molecular switches by alternating between inactive GDP-bound and active GTP-bound states. Ras activation is regulated by guanine nucleotide exchange factors that catalyze the exchange of GDP by GTP, and inactivation is terminated by GTPase-activating proteins that accelerate the intrinsic GTP hydrolysis rate by orders of magnitude. In this review, we focus on data that have accumulated over the past few years pertaining to the conformational ensembles and the allosteric regulation of Ras proteins and their interpretation from our conformational landscape standpoint. The Ras ensemble embodies all states, including the ligand bound conformations, the activated (or inactivated) allosteric modulated states, post-translationally modified states, mutational states, transition states, and nonfunctional states serving as a reservoir for emerging functions. The ensemble is shifted by distinct mutational events, cofactors, post-translational modifications, and different membrane compositions. A better understanding of Ras biology can contribute to therapeutic strategies. PMID- 26815309 TI - Development and Testing of a Magnetically Actuated Capsule Endoscopy for Obesity Treatment. AB - Intra-gastric balloons (IGB) have become an efficient and less invasive method for obesity treatment. The use of traditional IGBs require complex insertion tools and flexible endoscopes to place and remove the balloon inside the patient's stomach, which may cause discomfort and complications to the patient. This paper introduces a new ingestible weight-loss capsule with a magnetically remote-controlled inflatable and deflatable balloon. To inflate the balloon, biocompatible effervescent chemicals are used. As the source of the actuation is provided via external magnetic fields, the magnetic capsule size can be significantly reduced compared to current weight-loss capsules in the literature. In addition, there are no limitations on the power supply. To lose weight, the obese subject needs only to swallow the magnetic capsule with a glass of water. Once the magnetic capsule has reached the patient's stomach, the balloon will be wirelessly inflated to occupy gastric space and give the feeling of satiety. The balloon can be wirelessly deflated at any time to allow the magnetic capsule to travel down the intestine and exit the body via normal peristalsis. The optimal ratio between the acid and base to provide the desired gas volume is experimentally evaluated and presented. A prototype capsule (9.6mm x 27mm) is developed and experimentally validated in ex-vivo experiments. The unique ease of delivery and expulsion of the proposed magnetic capsule is slated to make this development a good treatment option for people seeking to lose excess weight. PMID- 26815310 TI - Usefulness of PET Imaging to Guide Treatment Options in Gliomas. AB - OPINION STATEMENT: Magnetic resonance imaging (MRI) is the gold standard guiding diagnostic and therapeutic management in glioma with its high resolution and possibility to depict blood-brain-barrier disruption when contrast medium is applied. In light of the shifting paradigms revealing distinct tumor subtypes based on the molecular and genetic characterization and increasing knowledge about the variability of glioma biology, additional imaging modalities such as positron emission tomography (PET) depicting metabolic processes gain further importance in the management of glioma. PMID- 26815311 TI - Diagnosis of Rejection by Analyzing Ventricular Late Potentials in Heart Transplant Patients. AB - BACKGROUND: Heart transplant rejection originates slow and fragmented conduction. Signal-averaged ECG (SAECG) is a stratification method in the risk of rejection. OBJECTIVE: To develop a risk score for rejection, using SAECG variables. METHODS: We studied 28 transplant patients. First, we divided the sample into two groups based on the occurrence of acute rejection (5 with rejection and 23 without). In a second phase, we divided the sample considering the existence or not of rejection in at least one biopsy performed on the follow-up period (rejection pm1: 18 with rejection and 10 without). RESULTS: On conventional ECG, the presence of fibrosis was the only criterion associated with acute rejection (OR = 19; 95% CI = 1.65-218.47; p = 0.02). Considering the rejection pm1, an association was found with the SAECG variables, mainly with RMS40 (OR = 0.97; 95% CI = 0.87-0.99; p = 0.03) and LAS40 (OR = 1.06; 95% IC = 1.01-1.11; p = 0.03). We formulated a risk score including those variables, and evaluated its discriminative performance in our sample. The presence of fibrosis with increasing of LAS40 and decreasing of RMS40 showed a good ability to distinguish between patients with and without rejection (AUC = 0.82; p < 0.01), assuming a cutoff point of sensitivity = 83.3% and specificity = 60%. CONCLUSION: The SAECG distinguished between patients with and without rejection. The usefulness of the proposed risk score must be demonstrated in larger follow-up studies. PMID- 26815312 TI - Resilience in Patients with Ischemic Heart Disease. AB - BACKGROUND: Resilience is a psychosocial factor associated with clinical outcomes in chronic diseases. The relationship between this protective factor and certain diseases, such heart diseases, is still under-explored. OBJECTIVE: The present study sought to investigate the frequency of resilience in individuals with ischemic heart disease. METHOD: This was a cross-sectional study with 133 patients of both genders, aged between 35 and 65 years, treated at Rio Grande do Sul Cardiology Institute - Cardiology University Foundation, with a diagnosis of ischemic heart disease during the study period. Sixty-seven patients had a history of acute myocardial infarction. The individuals were interviewed and evaluated by the Wagnild & Young resilience scale and a sociodemographic questionnaire. RESULTS: Eighty-one percent of patients were classified as resilient according to the scale. CONCLUSION: In the sample studied, resilience was identified in high proportion among patients with ischemic heart disease. PMID- 26815313 TI - Alternatives to Aerobic Exercise Prescription in Patients with Chronic Heart Failure. AB - BACKGROUND: Exercise is essential for patients with heart failure as it leads to a reduction in morbidity and mortality as well as improved functional capacity and oxygen uptake (vO2). However, the need for an experienced physiologist and the cost of the exam may render the cardiopulmonary exercise test (CPET) unfeasible. Thus, the six-minute walk test (6MWT) and step test (ST) may be alternatives for exercise prescription. OBJECTIVE: The aim was to correlate heart rate (HR) during the 6MWT and ST with HR at the anaerobic threshold (HRAT) and peak HR (HRP) obtained on the CPET. METHODS: Eighty-three patients (58 +/- 11 years) with heart failure (NYHA class II) were included and all subjects had optimized medication for at least 3 months. Evaluations involved CPET (vO2, HRAT, HRP), 6MWT (HR6MWT) and ST (HRST). RESULTS: The participants exhibited severe ventricular dysfunction (ejection fraction: 31 +/- 7%) and low peak vO2 (15.2 +/- 3.1 mL.kg-1.min-1). HRP (113 +/- 19 bpm) was higher than HRAT (92 +/- 14 bpm; p < 0.05) and HR6MWT (94 +/- 13 bpm; p < 0.05). No significant difference was found between HRP and HRST. Moreover, a strong correlation was found between HRAT and HR6MWT (r = 0.81; p < 0.0001), and between HRP and HRST (r = 0.89; p < 0.0001). CONCLUSION: These findings suggest that, in the absence of CPET, exercise prescription can be performed by use of 6MWT and ST, based on HR6MWT and HRST. PMID- 26815314 TI - Steatohepatitis and liver fibrosis are predicted by the characteristics of very low density lipoprotein in nonalcoholic fatty liver disease. AB - BACKGROUND & AIMS: A major challenge in the management of nonalcoholic fatty liver disease (NAFLD) is to identify patients with nonalcoholic steatohepatitis (NASH) and early liver fibrosis. The progression of NAFLD is accompanied by distinctive changes in very low density lipoprotein (VLDL), a lipoprotein particle produced exclusively in the liver. Herein, we sought to determine the characteristics of VLDL profiles associated with NASH and liver fibrosis. METHODS: We evaluated VLDL profiles of 128 patients from a single centre NAFLD registry, and examined VLDL size, total and subclass VLDL concentrations in relation to NAFLD activity score (NAS), steatohepatitis and liver fibrosis as determined by liver biopsy. RESULTS: A near linear relationship was observed between mean VLDL particle size and NAFLD activity score (NAS). In multivariate models, VLDL particle size was significantly associated with both NAS and NASH, after adjustment for BMI and diabetes. A decrease in small VLDL particle concentration was associated with more advanced liver fibrosis. In receiver operative characteristic analyses, mean VLDL size performed similarly to cytokeratin 18 in predicting NASH, whereas small VLDL particle concentration had similar performance to NAFLD fibrosis score in predicting stage 2 or above liver fibrosis. CONCLUSIONS: The increase in mean VLDL size in NASH and decrease in small VLDL particle concentration in liver fibrosis likely reflect changes in the number and state of hepatocytes associated with NASH and fibrosis. In addition to its value in risk stratification of cardiovascular diseases, circulating VLDL profile may provide information for the staging of NAFLD disease severity. PMID- 26815315 TI - Evaluation of kidney injury biomarkers in rat amniotic fluid after gestational exposure to cadmium. AB - Cadmium is a well-characterized nephrotoxic agent that is also capable of accumulating and diffusing across the placenta; however, only a few studies have addressed its effects over fetal kidneys and none of them has used a panel of sensitive and specific biomarkers for the detection of kidney injury. The goal of this study was to determine cadmium renal effects in rat fetuses by the quantification of early kidney injury biomarkers. Pregnant Wistar rats were exposed by inhalation to an isotonic saline solution or to CdCl2 solution (DDel =1.48 mg Cd kg(-1) day(-1) ) during gestational days (GD) 8-20. On GD 21, dams were euthanized and samples obtained. Kidney injury biomarkers were quantified in amniotic fluid samples and fetal kidneys were microscopically evaluated to search for histological alterations. Our results showed that cadmium exposure significantly raised albumin, osteopontin, vascular endothelial growth factor and tissue inhibitor of metalloproteinases-1 levels in amniotic fluid, whereas it decreased creatinine. Clusterin, calbindin and IFN-inducible protein 10 did not show any change. Accordingly, histological findings showed tubular damage and precipitations in the renal pelvis. In conclusion, gestational exposure to cadmium induces structural alterations in fetal renal tissue that can be detected by some kidney injury biomarkers in amniotic fluid samples. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26815316 TI - A Novel Layered Sedimentary Rocks Structure of the Oxygen-Enriched Carbon for Ultrahigh-Rate-Performance Supercapacitors. AB - In this paper, gelatin as a natural biomass was selected to successfully prepare an oxygen-enriched carbon with layered sedimentary rocks structure, which exhibited ultrahigh-rate performance and excellent cycling stability as supercapacitors. The specific capacitance reached 272.6 F g(-1) at 1 A g(-1) and still retained 197.0 F g(-1) even at 100 A g(-1) (with high capacitance retention of 72.3%). The outstanding electrochemical performance resulted from the special layered structure with large surface area (827.8 m(2) g(-1)) and high content of oxygen (16.215 wt %), which effectively realized the synergistic effects of the electrical double-layer capacitance and pseudocapacitance. Moreover, it delivered an energy density of 25.3 Wh kg(-1) even with a high power density of 34.7 kW kg( 1) and ultralong cycling stability (with no capacitance decay even over 10,000 cycles at 2 A g(-1)) in a symmetric supercapacitor, which are highly desirable for their practical application in energy storage devices and conversion. PMID- 26815317 TI - Editorial: A Stalemate in Lupus-Related End-Stage Renal Disease: Can We Do Better? PMID- 26815319 TI - Multivariate Analysis Of Gang Delinquency: Iv. Personality Factors In Gangs And Clubs. AB - A sample of gang members and a comparison group of club boys are compared on eleven factors from the Objective-Analytic Personality Factor Battery. It is found that gang and club boys differ significantly on five of the personality factors, with club boys being more assertive, more exuberant, and more realistic. The gang boys show more manic smartness and less self-realization. Possible relationships between these variables and type of delinquent behavior are examined. Three factors (assertiveness, alertness, and stolidness) do show significant differences between gang boys engaged in different types of delinquent behavior. However, no simple linear relationships are found between personality factors and delinquent behaviors in gangs. The findings are examined in the light of several hypotheses drawn from theories of personality and of gang delinquency. PMID- 26815320 TI - The Logical Paradox Of Order Analysis. AB - Order analysis, a technique to isolate unidimensional hierarchies representing multidimensional structure of binary data, is reviewed. Several theoretical flaws inherent to the probalistic version are presented. Suggestions of possible directions for future research are offered. PMID- 26815318 TI - Capture and On-chip analysis of Melanoma Cells Using Tunable Surface Shear forces. AB - With new systemic therapies becoming available for metastatic melanoma such as BRAF and PD-1 inhibitors, there is an increasing demand for methods to assist with treatment selection and response monitoring. Quantification and characterisation of circulating melanoma cells (CMCs) has been regarded as an excellent non-invasive candidate but a sensitive and efficient tool to do these is lacking. Herein we demonstrate a microfluidic approach for melanoma cell capture and subsequent on-chip evaluation of BRAF mutation status. Our approach utilizes a recently discovered alternating current electrohydrodynamic (AC-EHD) induced surface shear forces, referred to as nanoshearing. A key feature of nanoshearing is the ability to agitate fluid to encourage contact with surface bound antibody for the cell capture whilst removing nonspecific cells from the surface. By adjusting the AC-EHD force to match the binding affinity of antibodies against the melanoma-associated chondroitin sulphate proteoglycan (MCSP), a commonly expressed melanoma antigen, this platform achieved an average recovery of 84.7% from biological samples. Subsequent staining with anti BRAF(V600E) specific antibody enabled on-chip evaluation of BRAF(V600E) mutation status in melanoma cells. We believe that the ability of nanoshearing-based capture to enumerate melanoma cells and subsequent on-chip characterisation has the potential as a rapid screening tool while making treatment decisions. PMID- 26815321 TI - Cognitive Abilities As Expressions Of Three "Ways Of Knowing". AB - Factor analytic studies suggest that there are six replicable second order cognitive factors. These six factors lend themselves to being interpreted as aspects of Royce's (1964) three "ways of knowing." This view provides a unified explanation of the second and third order factors. We hypothesize that each second order factor represents either the number of cognitive schemata of a particular type that a person possesses or the quality of these schemata, and the types of schemata are linked to "ways of knowing." The division of second order factors into qualitative and quantitative aspects, with the qualitative aspects being more subject to deterioration with age, and the quantitative aspects more trainable and subject to personality influence, provides an avenue for linking cognitive abilities to the other personality traits. The theory also resolves several theoretical problems concerning cognitive abilities, including distinguishing aptitudes from achievements, measuring creativity, and determining the relationship between rote memory and intelligence. PMID- 26815322 TI - A Measure Of Separability And Random Zeros In Statistical Classification. AB - The setting for this study is the two-group multinomial classification problem. Based on a measure of the log odds in favor of one particular group, a large sample confidence interval for a measure of separability is derived. The asymptotic result employed assumes that all states have positive observed frequencies. Realizing that this assumption is often violated, we consider a method based upon log-linear representation of state frequencies to first remove any random zeros before attempting to effect a classification. The method is illustrated in a data set dealing with the behavioral consequences following hypoxic trauma. PMID- 26815323 TI - Scalogram And Factor Analyses Of Two Tests Of Cognitive Development. AB - Two tests of cognitive development, the Cartoon Conservation Scales (CCS), Levels I and II, were designed to measure Piagetian stage-related constructs for children of different age groups (De Avila, 1976). The tests were factor analyzed within age level and were also analyzed using scalogram and tabular methods to test sequential hypotheses. The appropriateness of these two methodological approaches to the analysis of developmental data was discussed and results were compared. It was noted that factor differentiation appears to be related to Wohlwill's (1973) concept of divergent horizontal decalage, or increasing lag in the mastery of construct pairs which are theoretically germane to the same level of cognitive functioning. PMID- 26815324 TI - Negative Similarities Versus Correlational Similarities. AB - The relationship between correlational similarities and negative similarities was studied on political perception data. One sample of 199 subjects gave estimates of the degree of positive similarity among stimuli. The columns of the mean similarity were intercorrelated, yielding a matrix of correlational similarities. Another sample of 148 subjects gave also similarity estimates among the same stimuli but were allowed to express negative similarities when stimuli were perceived as opposite to each other, yielding a matrix of mean negative similarities. The linear relationship between corresponding elements in the two matrices was very high (r = .954). Further, a dimension analysis on respective data gave three corresponding, highly congruent dimensions. Implications of the high congruence between correlational and negative similarities are discussed. PMID- 26815325 TI - Confidence Intervals For Maximized Alpha Coefficients: An Evaluation Of Joe And Woodward's Procedures And An Alternative Method. AB - The procedures yielding confidence intervals for maximized alpha coefficients of Joe and Woodward are reviewed. Confidence interval procedures of Hakstian, Whalen, and Masson are next reviewed. Results are then presented of a Monte Carlo investigation of the procedures. Of Joe and Woodward's procedures, that derived for the most general case is shown to yield confidence intervals spanning the parameter with probabilities adequately close to nominal values. This procedure is shown to perform as well as Joe and Woodward's second procedure -- for the equicorrelation case -- even with equicorrelation data. Hakstian et al's method is also shown to yield adequately precise intervals. The results are discussed, and implications for research noted. PMID- 26815326 TI - A Confirmatory Approach To Calibration Congeneric Measures. AB - This paper demonstrates how the problem of calibrating measures can be formulated in terms of confirmatory factor analysis. The relationships between traditional approaches (Angoff, 1971) and a confirmatory factor approach are specified. PMID- 26815327 TI - Outcomes of Elbow Arthroscopic Osteocapsular Arthroplasty. AB - PURPOSE: To evaluate the results of elbow arthroscopic osteocapsular arthroplasty (AOA) and determine which factors influence the outcome in a large group of patients with primary osteoarthritis. METHODS: A consecutive series of 46 patients with elbow osteoarthritis underwent AOA by a single surgeon (N.G.H.) between December 2005 and January 2013. Thirty-one patients returned for a comprehensive physical examination an average of 3.4 years later. The outcomes measures included visual analog scale (VAS), Mayo Elbow Performance Scores (MEPS), Disabilities of the Arm, Shoulder, and Hand (DASH), and American Shoulder and Elbow Society (ASES) scores. Preoperative and postoperative continuous variables were compared and a multivariable regression analysis was performed. RESULTS: Thirty-one patients with a mean age of 48 years (range, 19-77 years) returned for final follow-up, including 27 men and 4 women. Statistically significant improvement was observed in extension deficit (24 degrees before surgery to 12 degrees after surgery), flexion (126 degrees before surgery to 135 degrees after surgery), visual analog scale (6.4 before surgery to 1.6 after surgery), and Mayo Elbow Performance Scores (57 [poor] before surgery to 88 [good] after surgery). Subjective scores included a mean postoperative Disabilities of the Arm, Shoulder, and Hand score of 13 and an American Shoulder and Elbow Society pain score of 40. No complications were noted at final follow up. CONCLUSIONS: Elbow AOA is a safe, efficacious treatment for patients with mild to moderate osteoarthritis. Our retrospective review found significant improvement in elbow motion, pain and clinical outcomes. PMID- 26815328 TI - Radiographic Parameters to Predict Union After Volar Percutaneous Fixation of Herbert Type B1 and B2 Scaphoid Fractures. AB - PURPOSE: To study the angle of screw placement in relation to the scaphoid fracture plane and its effect on union after percutaneous fixation of scaphoid waist fractures. METHODS: Twenty-four consecutive scaphoid waist fractures were retrospectively evaluated for the orientation of screws in relation to the fracture plane using a method in which the sum-of-smaller angles (SSA) in 3 different radiographs were used to correlate with time to fracture union. RESULTS: All but one patient achieved union after percutaneous fixation of the scaphoid. Another patient required revision surgery within the study period for inadequate fixation. A shortened time to union was significantly correlated to larger SSA. CONCLUSIONS: SSA may be a reasonable predictor of union after percutaneous fixation of scaphoid waist fracture. It can be reliably calculated using plain radiographs. An SSA of 190 degrees or more correlated with union by 8 weeks postoperatively. PMID- 26815329 TI - Letter Regarding "Comparison of Flexor Tendon Suture Techniques Including 1 Using 10 Strands". PMID- 26815330 TI - In Reply. PMID- 26815331 TI - US Preventive Services Task Force Recommendation Statement on Screening for Depression in Adults: Not Good Enough. PMID- 26815332 TI - Critical Nucleus Structure and Aggregation Mechanism of the C-terminal Fragment of Copper-Zinc Superoxide Dismutase Protein. AB - The aggregation of the copper-zinc superoxide dismutase (SOD1) protein is linked to familial amyotrophic lateral sclerosis, a progressive neurodegenerative disease. A recent experimental study has shown that the (147)GVIGIAQ(153) SOD1 C terminal segment not only forms amyloid fibrils in isolation but also accelerates the aggregation of full-length SOD1, while substitution of isoleucine at site 149 by proline blocks its fibril formation. Amyloid formation is a nucleation polymerization process. In this study, we investigated the oligomerization and the nucleus structure of this heptapeptide. By performing extensive replica exchange molecular dynamics (REMD) simulations and conventional MD simulations, we found that the GVIGIAQ hexamers can adopt highly ordered bilayer beta-sheets and beta-barrels. In contrast, substitution of I149 by proline significantly reduces the beta-sheet probability and results in the disappearance of bilayer beta-sheet structures and the increase of disordered hexamers. We identified mixed parallel-antiparallel bilayer beta-sheets in both REMD and conventional MD simulations and provided the conformational transition from the experimentally observed parallel bilayer sheets to the mixed parallel-antiparallel bilayer beta sheets. Our simulations suggest that the critical nucleus consists of six peptide chains and two additional peptide chains strongly stabilize this critical nucleus. The stabilized octamer is able to recruit additional random peptides into the beta-sheet. Therefore, our simulations provide insights into the critical nucleus formation and the smallest stable nucleus of the (147)GVIGIAQ(153) peptide. PMID- 26815333 TI - Superconducting Calcium-Intercalated Bilayer Graphene. AB - We report the direct evidence for superconductivity in Ca-intercalated bilayer graphene C6CaC6, which is regarded as the thinnest limit of Ca-intercalated graphite. We performed the electrical transport measurements with the in situ 4 point-probe method in ultrahigh vacuum under zero- or nonzero-magnetic field for pristine bilayer graphene, Li-intercalated bilayer graphene (C6LiC6) and C6CaC6 fabricated on SiC substrate. We observed that the zero-resistance state occurs in C6CaC6 with the onset temperature (T(c)(onset)) of 4 K, while the T(c)(onset) is gradually decreased upon applying the magnetic field. This directly proves the superconductivity origin of the zero resistance in C6CaC6. On the other hand, both pristine bilayer graphene and C6LiC6 exhibit nonsuperconducting behavior, suggesting the importance of intercalated atoms and its species to drive the superconductivity. PMID- 26815334 TI - Cytoreductive surgery in the era of targeted molecular therapy. AB - Cytoreductive nephrectomy (CN) was regarded standard of care for patients with metastatic renal cell carcinoma (mRCC) in the immunotherapy era. With the advent of targeted molecular therapy (TMT) for the treatment of mRCC, the routine use of CN has been questioned. Up to date evidence continues to suggest that CN remains an integral part of treatment in appropriately selected patients. This review details the original context in which the efficacy of CN was established and rationale for the continued use of cytoreductive surgery in the era of TMT. PMID- 26815335 TI - Bi-template assisted synthesis of mesoporous manganese oxide nanostructures: Tuning properties for efficient CO oxidation. AB - A simple soft bi-templating process was used for the synthesis of mesoporous manganese oxide nanostructures using KMnO4 as a precursor and polyethylene glycol and cetyltrimethylammonium bromide as templates in the presence of benzaldehyde as an organic additive in alkaline media, followed by calcination at 400 degrees C. X-ray diffraction and Raman spectroscopic analysis of the calcined products confirmed the existence of stoichiometric (MnO2 and Mn5O8) and non-stoichiometric mixed phases (MnO2 + Mn5O8) of Mn oxides obtained by tuning the concentration of the additive and the synthesis time. The surface properties of the prepared Mn oxides were determined by X-ray photoelectron spectroscopy. The mesoporosity of the samples was confirmed by N2 adsorption-desorption. Different synthetic conditions resulted in the formation of different morphologies of the Mn oxides (alpha-MnO2, Mn5O8, and alpha-MnO2 + Mn5O8), such as nanoparticles, nanorods, and nanowires. The synthesized mesoporous Mn oxide nanostructures were used for the catalytic oxidation of the harmful air pollutant carbon monoxide. The Mn5O8 nanoparticles with the highest Brunauer-Emmett-Teller surface area and the non stoichiometric manganese oxide (alpha-MnO2 + Mn5O8) nanorods with a higher Mn(3+) concentration had the best catalytic efficiency. PMID- 26815336 TI - Low-Mode Conformational Search Method with Semiempirical Quantum Mechanical Calculations: Application to Enantioselective Organocatalysis. AB - A conformational search program for finding low-energy conformations of large noncovalent complexes has been developed. A quantitatively reliable semiempirical quantum mechanical PM6-DH+ method, which is able to accurately describe noncovalent interactions at a low computational cost, was employed in contrast to conventional conformational search programs in which molecular mechanical methods are usually adopted. Our approach is based on the low-mode method whereby an initial structure is perturbed along one of its low-mode eigenvectors to generate new conformations. This method was applied to determine the most stable conformation of transition state for enantioselective alkylation by the Maruoka and cinchona alkaloid catalysts and Hantzsch ester hydrogenation of imines by chiral phosphoric acid. Besides successfully reproducing the previously reported most stable DFT conformations, the conformational search with the semiempirical quantum mechanical calculations newly discovered a more stable conformation at a low computational cost. PMID- 26815337 TI - Synthesis of new dicinnamoyl 4-deoxy quinic acid and methyl ester derivatives and evaluation of the toxicity against the pea aphid Acyrthosiphon pisum. AB - New dicinnamoyl (caffeoyl, feruloyl, ortho and para-coumaroyl) 4-deoxyquinic acid and esters were synthesized by using a new 4-deoxy quinic acid triol intermediate. The optimisation of both coupling and deprotection steps allowed the preparation in good yields of the target products either as the carboxylic acid or the methyl ester form. Eight new compounds were evaluated for their ability to influence the feeding behaviour of the pea aphid Acyrthosiphon pisum. Artificial diet bioassays showed that two compounds are toxic (mortality and growth inhibition) at lower concentrations than the reference 3,5-dicaffeoyl quinic acid. PMID- 26815338 TI - Diagnosis of Acute Coronary Syndrome with a Support Vector Machine. AB - Acute coronary syndrome (ACS) is a serious condition arising from an imbalance of supply and demand to meet myocardium's metabolic needs. Patients typically present with retrosternal chest pain radiating to neck and left arm. Electrocardiography (ECG) and laboratory tests are used indiagnosis. However in emergency departments, there are some difficulties for physicians to decide whether hospitalizing, following up or discharging the patient. The aim of the study is to diagnose ACS and helping the physician with his decisionto discharge or to hospitalizevia machine learning techniques such as support vector machine (SVM) by using patient data including age, sex, risk factors, and cardiac enzymes (CK-MB, Troponin I) of patients presenting to emergency department with chest pain. Clinical, laboratory, and imaging data of 228 patients presenting to emergency department with chest pain were reviewedand the performance of support vector machine. Four different methods (Support vector machine (SVM), Artificial neural network (ANN), Naive Bayes and Logistic Regression) were tested and the results of SVM which has the highest accuracy is reported. Among 228 patients aged 19 to 91 years who were included in the study, 99 (43.4 %) were qualified as ACS, while 129 (56.5 %) had no ACS. The classification model using SVM attained a 99.13 % classification success. The present study showed a 99.13 % classification success for ACS diagnosis attained by Support Vector Machine. This study showed that machine learning techniques may help emergency department staff make decisions by rapidly producing relevant data. PMID- 26815340 TI - [Standard for specimen collection and reports of bacterial examination in low respiratory infection]. PMID- 26815339 TI - An Empirical Study of Neural Network-Based Audience Response Technology in a Human Anatomy Course for Pharmacy Students. AB - This paper presents an empirical study of a formative neural network-based assessment approach by using mobile technology to provide pharmacy students with intelligent diagnostic feedback. An unsupervised learning algorithm was integrated with an audience response system called SIDRA in order to generate states that collect some commonality in responses to questions and add diagnostic feedback for guided learning. A total of 89 pharmacy students enrolled on a Human Anatomy course were taught using two different teaching methods. Forty-four students employed intelligent SIDRA (i-SIDRA), whereas 45 students received the same training but without using i-SIDRA. A statistically significant difference was found between the experimental group (i-SIDRA) and the control group (traditional learning methodology), with T (87) = 6.598, p < 0.001. In four MCQs tests, the difference between the number of correct answers in the first attempt and in the last attempt was also studied. A global effect size of 0.644 was achieved in the meta-analysis carried out. The students expressed satisfaction with the content provided by i-SIDRA and the methodology used during the process of learning anatomy (M = 4.59). The new empirical contribution presented in this paper allows instructors to perform post hoc analyses of each particular student's progress to ensure appropriate training. PMID- 26815342 TI - [Colonization and infection of Staphylococcus aureus]. PMID- 26815341 TI - [A brief analysis on the relationship between sputum culture and pneumonia]. PMID- 26815343 TI - [The clinical and bacterial features of Klebsiella pnuemoniae liver abscess]. AB - OBJECTIVE: To summarize the clinical and bacterial features of Klebsiella pnuemoniae liver abscess (KPLA) in order to provide the basis for the diagnosis and treatment of KPLA. METHODS: Retrospective study was conducted. One hundred and fifty-two medical records, from 3 teaching hospitals in Beijing, between January 2010 and December 2014, were collected. Among which 137 complete medical records were analyzed. String test was carried out to detect the hypermucoviscosity phenotype. PCR was performed to check the capsular serotype and the virulent genes. Disk diffusion method was operated to obtain the antimicrobial resistance rates. The results were analyzed by chi-square test. RESULTS: KPLA occurred mostly in middle-aged, male and diabetes mellitus patients. 92.7% (127/137) patients had fever. 80.3% (110/137) of the KLPA were single abscess, among which 80.9% (89/110) were in the right lobe and 33.6% (46/137) had air cavities.74.5% (102/137) of the white blood cell count, 83.2% (114/137) of the neutrophils' percentage, 78.1% (107/137) of alanine aminotransferase and 51.8% (71/137) of the total billrubin were elevated. 87.5% (133/152) of the Klebsiella pnuemoniae (Kpn) appeared to be hypermucoviscous, K1 was the most popular serotype, the second was K2, and the positive rates of virulent genes rmpA and aerobactin were 82.9% (126/152) and 88.2% (134/152), respectively. Among the isolates from the KPLA without other hepatobiliary diseases, the portion of K1 serotype, the positive rates of rmpA and aerobactin were 65.7%, 94.9% and 96.0%, respectively, higher than those of the 28.9%, 50.0% and 68.4% from the KPLA with other hepatobiliary diseases, while the undefined serotype potion was lower (5.1% vs 26.3%), the differences were statistically significant (chi(2)=14.98, 38.40, 17.61, 10.65, all P<0.01). Most of Kpn were susceptible to antimicrobials. CONCLUSIONS: KPLA has certain clinical features, and are mostly caused by hypervirulent isolates that are hypermucoviscous with rmpA and aerobactin genes. Most of the isolates are susceptible to antimicrobials. PMID- 26815344 TI - [Study on genotype and clinical characteristics of infection of carbapenemase producing Enterobacter cloacae]. AB - OBJECTIVE: To study the genotypes and clinical characteristics of carbapenemase producing Enterobacter cloacae (E.cloacae), and lay the foundation for active control of nosocomial infection. METHODS: E.cloacae isolates were collected from January 2007 to December 2014. Strains which showed decreased sensitivity to carbapenem were screened out by the modified Hodge test (MHT) and EDTA-disk synergy test. The genotype of blaKPC, blaIMP, blaVIM, blaOXA-48 and blaNDM-1 were detected by PCR amplication, the product of PCR was sequenced and conducted by Blast (http://blast.ncbi.nlm.nih.gov/Blast.cgi). Conjugal transfer experiment was conducted to prove horizontal transmit of carbapenemase gene produced by E.cloacae. Meanwhile, the clinical epidemiological data of patients infected by selected strains were also analyzed. RESULTS: Sixty-four carbapenemase producing E.cloacae were detected by MHT, EDTA-disk synergy test and PCR amplification. Forty-five strains (70.3%) out of 64 strains infection came from nosocomial infection, while 19 strains (29.7%) from the community infection. The strains were mainly isolated from secretions samples and sputum samples, which accounted for 65.6% (42/64) and 23.4% (15/64) separately. The mainly clinical departments were orthopaedics (43.8%), department of burn (21.9%), ICU (18.8%) and pediatrics (14.1%). Bed changing, invasive operation and indwelling catheter were risk factors for the transmission of carbapenemase producing E.cloacae, and infected patients had longer time of staying in hospital, lower cure rate and higher frequency of cephalosporins enzyme inhibitor compound or carbapenem agents administration (all P<0.05). Sixty-four strains showed increased MIC to most of the antibiotics except for polymyxin and tigecycline. Among the 64 strains, 29 strains were genotype blaIMP-4 and 35 strains were genotype blaIMP-8 by Blast alignment, no genotype blaVIM, blaOXA-48 and blaNDM-1 were detected. Result of conjugal transfer experiment showed that receptor strain obtained carbapenem resistance, and the sequence of resistance gene of receptor strain was the same to the donator strain. CONCLUSIONS: The drug resistance of E.cloacae are growing, IMP-4 and IMP-8 carbapenemase are the main enzymes produced by strains. As the resistance gene can horizontal transmit between strains through conjugal transfer system, the strains have been locally spread in hospital departments, thus it is important to control risk factors of transmission timely. PMID- 26815345 TI - [Study on the molecular epidemiology of bacterial infection in patients in cardiac surgical intensive care unit]. AB - OBJECTIVE: To investigate the molecular epidemiology of acinetobacter baumannii and pseudomonas aeruginosa isolated from clinical specimens from patients on mechanical ventilation. METHODS: From October to December, 2012, acinetobacter baumannii and pseudomonas aeruginosa strains were isolated from patients on mechanical ventilation. Antibiotic susceptibility data of all strains was collected. Homology of the strains was analyzed by the methods of pulsed field gel electrophoresis (PFGE) genotype, meanwhile, the clinical data was also analyzed. RESULTS: Of the 15 pathogens isolated from patients on mechanical ventilation, 7 acinetobacter baumannii strains had different genotypes, indicating specific clustering in a specific location, so acinetobacter baumannii should be a scattered infection or colonized strains. Parts of 8 pseudomonas aeruginosa strains came from the same clone and confirm the existence of cross infection of nosocomial infections. CONCLUSION: The result shows that nosocomial infection outbreak doesn't occur, there is a small range of cross-infection of pseudomonas aeruginosa. PMID- 26815346 TI - [Value of pulse oximetry for diagnosing obstructive sleep apnea-hypopnea syndrome and evaluation of the effect of the continuous positive airway pressure therapy]. AB - OBJECTIVE: To explore the value of pulse oximetry for diagnosing obstructive sleep apnea hypopnea syndrome (OSAHS) and evaluation of the effect of the continuous positive airway pressure (CPAP) therapy. METHODS: From January 2013 to March 2014, 244 OSAHS patients admitted to department of respiratory and critical care medicine of the first affiliated hospital of Fujian Medical University and department of respiratory and critical care medicine of People's Hospital of Peking University were recruited. According to apnea-hypopnea index (AHI), all patients were divided into mild, moderate and severe groups. The differences in pulse-associated indicators [nocturnal pulse elevation index (NPEI), namely counts of heart rate (HR) variation >6 bpm/h, average HR and standard deviation of HR] were compared among three groups before and after CPAP therapy. Spearman correlation analysis between pulse-associated indicators and AHI was performed to explore the optimal indicator. Receiver operating characteristic (ROC) curve were conducted and sensitivity and specificity were obtained. RESULTS: NPEI after CPAP treatment were significantly lower than before among all the three groups (mild group 15.4+/-12.4 vs 19.4+/-13.3, moderate group 15.4+/-9.1 vs 24.1+/-11.9, severe group 21.9+/-14.8 vs 48.8+/-20.3, all P<0.05); there were significant correlations of AHI with average HR, standard deviation of HR and NPEI (r=0.334, 0.337 and 0.660, respectively) (all P<0.05); ROC curve showed a NPEI of 30beat per hour had a sensitivity of 68.0% and a specificity of 73.0% in diagnosing OSAHS. CONCLUSION: Nocturnal oximetry could be a useful tool for screening OSAHS in clinical practice, and the NPEI can evaluate the efficacy of the CPAP therapy. PMID- 26815347 TI - [Occurrence and clinical characteristics of sleep apnea syndrome in heart failure patients with atrial fibrillation]. AB - OBJECTIVE: To evaluate the occurrence and clinical characteristics of sleep apnea syndrome (SAS) in heart failure (HF) patients with atrial fibrillation (AF). METHODS: From HF patients hospitalized in the First Affiliated Hospital of Nanjing Medical University during June 2012 and June 2014, subjects were recruited based on electrocardiography examination, including 110 patients with AF (coexisting AF group) and 105 parallel control patients without AF but with matched age, gender and body mass index (simple HF group). Comparison was made about the occurrence and characteristics of SAS between two groups. RESULTS: There was no statistical difference in causes of HF, complications, New York Heart Association class and basic medication between two groups. Compared with the patients in simple HF group, the patients in coexisting AF group had a significantly higher Epworth sleepiness scale score, larger cardiothoracic ratio (10.1+/-5.8 vs 8.2+/-5.5, 0.63+/-0.08 vs 0.57+/-0.07; both P<0.05), and shorter 6 minute walk distance [(305+/-70) vs (335+/-69) m, P<0.05]. There was no difference in left ventricular ejection fraction, left ventricular end-diastolic dimension and left ventricular end-systolic dimension between two groups. However, left atrial diameter was remarkably larger in coexisting AF group than that in simple HF group (P<0.05). The prevalence of SAS was higher in coexisting AF group than that in simple HF group (36.4% vs 20.0%, P<0.05). Compared with simple HF group, the coexisting AF group had a higher apnea/hypopnea index [4(1, 16) vs 3(1, 7) times/h, P<0.05]. No significant differences were detected between two groups among the rapid of eye movement sleep stage/total sleep time, arousal index, mean and lowest pulse oxygen saturation (SpO2) and oxygen desaturation index. CONCLUSION: HF patients with AF have a higher frequency of SAS, more severe daytime sleepiness and poorer physical activity than matched simple HF patients without AF. PMID- 26815348 TI - [Analysis of clinical feature of IgG4 related disease]. AB - OBJECTIVE: To summarize the clinical characteristics of IgG4 related disease. METHODS: A retrospective analysis of clinical manifestation, radiography and pathological information of patients diagnosed with IgG4 related disease in Beijing Hospital. RESULTS: Patients recruited in this study were 7 males and 7 females at the average age of (64.3+/-10.0) years old. Equal or greater than two organs were suffered in 10 patients. In these involved organs, pancreas was the most suffered organ with 10 times, bile duct and salivary gland was suffered 5 times respectively, lung was suffered 4 times and lacrimal gland was suffered 2 times. Laboratory examination of these 14 cases showed that 5 of these cases were with increased level of plasma IgG and all of the cases were with increased level of IgG4, 7 patients were with increased level of eosinophil count and 9 patients in 12 cases were with the increased level of IgE. All of the diagnosed patients were eusemia and 13 of them received the treatment of glucocorticoid. After usage of glucocorticoid, the clinical symptom and radiography findings were at great improvement, and the levels of IgG4 were decreased, but only two cases were down to normal level. CONCLUSIONS: IgG4 related disease is a kind of disease with various manifestation and multiple organs are commonly suffered. The increase of IgG, IgE levels and eosinophil count could be considered as diagnosis clues. PMID- 26815349 TI - [Expression of LATS mRNA in mantle cell lymphoma and its clinical significance]. AB - OBJECTIVE: To investigate the expression level of large tumor suppressor (LATS)1, LATS2 mRNA and its prognostic value in mantle cell lymphoma (MCL). METHODS: A total of 36 B-NHL cases (including MCL 16 cases, chronic lymphoblastic leukemia (CLL) 11 cases, splenic marginal zone cell lymphoma (SMZL) 9 cases) and 8 healthy donors were enrolled in this study from January 2008 to April 2011 in our Lymphoma Clinic Center. The mRNA level of Yap (effector of Hippo pathway) and LATS1, LATS2 mRNA were detected by using real-time quantitative PCR. Log expression values of real-time quantitative PCR data were used in this analysis. RESULTS: The YAP mRNA expression level in MCL, CLL and SMZL patient were significantly higher than that in health donor (lg: 1.97+/-0.79, 1.83+/-0.54, 2.12+/-0.42 vs 1.21+/-1.56, all P<0.05). The expression level of LATS1, LATS2 mRNA in MCL was significantly correlated with molecular cytogenetic aberrations, progression free survival (PFS) and overall survival (OS). The LATS1 expression level was statistically lower in the group of MCL with delection P53 than the group of MCL without delection P53 (lg: 0.75+/-0.27 vs 1.10+/-0.19, P=0.035). And the LATS1 expression level was statistically lower in the death group than the survival group (lg: 0.76+/-0.27 vs 1.15+/-0.17, P=0.026). The PFS and OS were significantly longer in the MCL patients with high level of LATS1 than that of other MCL patients ((70.4+/-32.7) vs (5.6+/-2.2) months, P=0.044; (123.8+/-22.0) vs (7.7+/-2.2) months, P=0.017). CONCLUSIONS: Hippo pathway is dysfunctional in B NHL, especially in MCL.The reduced expression of LATS1, LATS2 in MCL patients is associated with progressive disease, and might be an important prognostic factor in MCL. PMID- 26815350 TI - [Effect of laparoscopic hepatectomy and microwave ablation for colorectal liver metastases]. AB - OBJECTIVE: To investigate the treatment effect of laparoscopic hepatectomy and microwave ablation for colorectal liver metastases. METHODS: We retrospectively analyzed 126 patients who received treatment for colorectal liver metastases in our hospital during Jan. 2009 to Jan. 2015, and these patients were divided into laparoscopic surgical group (40 cases), microwave group (42 cases) and open surgical group (44 cases). The overall survival rate and disease-free survival rate were compared by using the Kaplan-Meier method. RESULTS: The operation time in three groups were (120+/-35), (55+/-20), (100+/-30) min, respectively. The blood loss in the three groups were (300+/-120), (100+/-25), (250+/-95) ml, respectively. The operation time, blood loss and hospital stay in microwave group were less than the other two groups (P<0.05). There was no significant difference in survival time and postoperative complications in these groups (P>0.05). CONCLUSIONS: Laparoscopic hepatectomy and microwave ablation in the treatment of colorectal liver metastases is effective compared to open hepatectomy. So the minimal invasive surgical techniques had benefit for patients with liver metastases from colorectal cancer. PMID- 26815351 TI - [Effects of lifestyle and quantitative nutrition interventions on individuals with prediabetes]. AB - OBJECTIVE: To explore the impact of lifestyle and quantitative nutrition intervention on individuals with prediabetes. METHODS: A total of 214 prediabetic patients from epidemiologic survey in Ximazhuang and Guangrunmen community centers in Nanchang from January 2011 to January 2012 were enrolled in the study. All the participants were randomly divided into two groups: the intervention group and the control group, with 107 patients in each group. Intensified lifestyle and quantitative nutrition interventions were carried out in the intervention group, and routine lifestyle intervention was carried out in control group. Height and weight were measured, and the body mass index (BMI) was calculated. Blood glucose was tested by glucose oxidase method, and glycosylated hemoglobin (HbA1c) was detected by high performance liquid chromatography. Various parameter changes were compared between two groups after two year's follow-up, and the outcome data of patients was collected. The study was approved by the Ethics Committee of the Third Hospital of Nanchang. RESULTS: There were no significant differences in each parameter between two groups before intervention (all P>0.05). No obvious change was found for the parameters in the control group after two year's follow-up (all P>0.05), but weight, BMI, fasting blood glucose, postprandial two-hour blood glucose and HbA1c decreased in the intervention group (P<0.05). There were 11 (13.1%) diabetic cases and 1 (1.2%) participant with normal glucose tolerance in the control group, and 3 (3.4%) diabetic cases and 7 (8.0%) participants with normal glucose tolerance in the intervention group (P<0.05). The risk of diabetes in two groups was performed using cox regression model analysis, and the primary end-point was the incidence of diabetes. The risk of diabetes in the control group was significantly higher than that in the intervention group [HR=3.903, 95% CI: 1.089-13.992, P=0.037]. CONCLUSION: The lifestyle and quantitative nutrition interventions may improve the blood glucose control and delay the progression of diabetes in prediabetes patients. PMID- 26815352 TI - [Bortezomib-induced peripheral neuropathy in multiple myeloma patients]. AB - OBJECTIVE: To describe the side effects of bortezomib in treatment of multiple myeloma (MM), especially the incidence of peripheral neuropathy (PN). METHODS: Information of 107 patients with MM who were treated with bortezomib in the First Affiliated Hospital of Zhejiang University from 2009 to 2014, were collected and analyzed retrospectively, to analyze the occurrence of adverse events during the treatment, especially the incidences of PN in each cycle and in different patients. RESULTS: A total of 40 (37%) patients suffered from PN, among which 13 patients were grade 3 PN and no patients reported grade 4 PN. Other common treatment-related side effects were thrombocytopenia, gastrointestinal reactions, fatigue, lung infection, herpes zoster in turn. In 44 MM patients treated strictly with bortezomib 1.3 mg/m(2) (days 1, 4, 8, 11) of each 3-week cycle, 20(45%) patients suffered from PN, of which 6 (14%) patients got grade 3 PN. In other 63 patients who received bortezomib less than 1.3 mg/m(2), 20 (32%) patients got PN and 7(11%) patients were grade 3 PN. There was no significant difference in the incidence of PN between the two groups of MM patients mentioned above (P=0.149), as well as the incidence of grade 3 PN (P=0.694). Univariate and multivariate analyse revealed that gender, age, a history of hypertensive disease, diabetes or hepatitis B virus infection, baseline PN symptoms and a history of neurotoxicity drug therapy were all not risk factors for PN (all P>0.05). CONCLUSIONS: The reduction of bortezomib do not decrease the incidence of PN in bortezomib treatment of MM. Age, a history of diabetes and baseline PN symptoms are not risk factors for PN in bortezomib treatment of MM. PMID- 26815353 TI - [Survey of hospital infection management staff in the Inner Mongolia Autonomous Region]. AB - OBJECTIVE: To study the status of hospital infection management staff of the Inner Mongolia Autonomous Region. METHODS: The respondents completed the unified questionnaire. The person entered into the computer after checking, using EXCEL software for analysis. RESULTS: This survey involved 341 hospital infection management staffs, with an average age of 41.59 years. Professional background in nursing accounted for 59.53%. Bachelor degree or above accounted for 52.20%.The number of senior professional titles accounted for 40.47%. 78.09% of the staffs did not involve in the research. 36.58% of the staffs had special training or experience to lecture. Received provincial and national professional training staff accounted for 41.08% and 13.62%. Never received professional training in management of hospital infection accounted for 27.70%. 59.95% of the staff was never participated in academic exchanges. CONCLUSION: The hospital should give appropriate preferential treatment to the hospital infection management department in term of introduction of talent, job promotion, research, conference expenses and so on. Construction of a high-quality management team to improve the hospital infection management in our region. PMID- 26815354 TI - [Clinical analysis of renal cell carcinoma with brain metastases (report of 10 cases)]. AB - OBJECTIVE: To investigate the optimal treatment and prognostic factors of renal cell carcinoma with brain metastases (RCCBM) by the analysis of clinical features. METHODS: The clinical data of 10 patients with RCCBM in our hospital from Jul. 2003 to Aug. 2011 were analyzed retrospectively. The age range of the patients was 48-80 years, and the mean age was 64 years old. Nine patients were male and one patient was female. Six patients had neurological symptoms. Brain metastasis and kidney cancer were found in the same period in 7 patients. Two patients had brain metastases alone, and 8 patients had metastasis in brain and other parts. There were 4 patients had more than 3 brain metastatic foci. Brain metastatic foci located in: frontal lobe in 6 patients, parietal lobe in 2 patients, occipital lobe in 2 patients, cerebellum in 2 patients, temporal lobe in 1 patient, thalamus and basal ganglia in 1 patient. RESULTS: The overall survival (OS) of 10 patients with RCCBM was 0.8 to 62.6 months, with an average OS of 12.7 months. Two patients refused therapy and those average OS is only 1.4 months. Three patients were performed stereotactic radiotherapy (SRS). The tumor volume of 1 patient reduced >25% and 2 patients showed no progression in magnetic resonance images at 2-months after SRS. Two patients accepted sorafenib treatment and the average OS was 16.7 months. Patients with 3 or more brain metastases had an average OS of 1.9 months, and the average OS of those with less than 3 brain metastases was 20 months. Patients with synchronous or metachronous brain metastases of renal cell carcinoma had an average OS of 6.8 or 26.5 months, respectively. Patients with or without neurological symptoms had an average OS of 17.9 or 4.9 months, respectively. CONCLUSIONS: For RCCBM patients, SRS could effectively control the local brain metastases while sorafenib could extend the overall survival. With 3 or more metastases, synchronous brain metastases and no neurological symptoms were the adverse prognostic factors of RCCBM. PMID- 26815355 TI - [Effects of NVP-BKM120 on the triple-negative breast cancer cell]. AB - OBJECTIVE: To investigatethe effect of NVP-BKM120 on the triple-negative breast cancer cell lines. METHODS: Breast cancer cell line MDA-MB-231 and Cal51 were divided into control group and experimental group. The inhibitory effects of BKM120 were evaluated by MTT assays. The drug effects on CSC population and characteristics were investigated through mammosphere formation assay and colony formation assay. Western blot was used to observe the expressionof related protein. The BALB/c mice were injected with stem cells (SCs) and different treatments were administered subsequently. RESULTS: In MDA-MB-231 cell lines, IC50 of BKM120 was (20.01+/-3.46) umol/L for SCs and (3.07+/-0.14) umol/L for total cells. BKM120 significantly inhibit the cell growth, in vitrocloning and microspheres formed of triple-negative breast cancer cells. BKM120 can inhibit tumor growth in nude mice without significant adverse reactions. CONCLUSION: BKM120 can significantly inhibit the proliferation of the triple-negative breast cancer cell lines. PMID- 26815357 TI - Rosacea patients seeking advice: Qualitative analysis of patients' posts on a rosacea support forum. AB - BACKGROUND: Social media have become outlets for patients to voice opinions and ask questions. Since suffering from rosacea is an isolating experience and the disease is poorly understood, patients use social media to expand their knowledge about the condition. OBJECTIVE: To understand rosacea patients' online health information seeking habits to obtain a better insight of their educational needs. METHODS: Ten percent of posts in online rosacea forum composed of 3350 members and 27 051 posts, discussing patient viewpoints and concern, selected by stratified random sampling. Three hundred and nine queries were directly categorized to patients "seeking advice" by two investigators and qualitatively analyzed. RESULTS: Patients primarily sought advice about treatments (n = 155, 50.1%), triggers (n = 53, 17.1%), diet (n = 48, 15.5%), skin care (n = 37, 11.9%) and special presentations of the disease (n = 22, 7.1%). Questions frequently pertained to adverse effects, efficacy and target of therapy (78, 49, 30 posts, respectively). CONCLUSION: Proactively providing reliable resources and comprehensive explanations on treatments, triggers, diet and skin care could be helpful in reducing patients' confusion about rosacea and enhancing rosacea patient-physician relationships. PMID- 26815356 TI - [Protective effects of metformin on glomerular podocytes of type 2 diabetes model rats]. AB - OBJECTIVE: To observe the effects of metformin (MET) on podocalyxin (PCX) expression in renal tissue from type 2 diabetes mellitus (T2DM) model rats and investigate its protective effects against glomerular podocyte injury. METHOD: The rat model of T2DM was established by feeding with high-fat diet and intraperitoneal injection of low dose of streptozotocin (STZ). All the rats were divided into four groups: diabetic group (n=9), metformin group (300 mg.kg(-1).d( 1), n=8), glibenclamide group (5 mg.kg(-1).d(-1), n=8 ) and normal group (n=8). After 8 weeks, urinary PCX and creatinine, blood glucose (BG) and glycated hemoglobin (HbA1c) were detected in all the rats. Immunohistochemistry was used to observe the protein expression of PCX in renal tissue. Real-time polymerase chain reaction (PCR) was performed to detect mRNA expression of PCX. Pathological changes of renal tissue were observed by electron microscope. RESULTS: Metformin and glyburide treatment decreased the levels of BG and HbA1c [(9.6+/-1.1) and (9.9+/-1.1) vs (15.6+/-1.6) mmol/L, (7.0+/-0.3)% and (8.0+/-1.0)% vs (12.4+/ 0.6)%, all P<0.05], compared with diabetes group, while there was no statistically significant difference between the two intervention groups (P>0.05). The level of urinary PCX/urinary creatinine (UPCR) in diabetic rats were higher than that of normal group [(697+/-136) vs (94+/-25 ) ng/g, P<0.05), meanwhile the levels of protein and mRNA expression of PCX in kidney tissue reduced remarkably [(0.75+/-0.11) vs (3.18+/-0.14), (0.08+/-0.09) vs (1.00+/ 0.02), both P<0.05]. Above-mentioned indicators could be ameliorated by metformin and glyburide treatment compared to normal group (P<0.05), and there were statistically significant difference between the two intervention groups [(404+/ 83) vs (516+/-38) ng/g, (1.54+/-0.06) vs(1.06+/-0.10), (0.23+/-0.01) vs (0.16+/ 0.04), all P<0.05)]. Further observation found that basement membrane thickness of kidney [(267+/-22) vs (106+/-10)nm )] and fusion rate of foot process (0.80+/ 0.07 vs 0) increased in the rats of diabetic group, and metformin or glyburide treatment can significantly reduced the above changes (P<0.05), additionally, the changes were remarkable different between metformin and glyburide group [(151+/ 17) vs (204+/-22 ) nm, (0.49+/-0.04) vs (0.57+/-0.03), both P<0.05)]. CONCLUSION: Metformin has protective effect on glomerular podocytes by regulating the expression of PCX in renal tissue, independent of its hypoglycemic effect. PMID- 26815358 TI - Inactivation of Francisella tularensis Gene Encoding Putative ABC Transporter Has a Pleiotropic Effect upon Production of Various Glycoconjugates. AB - Francisella tularensis, an intracellular pathogen causing the disease tularemia, utilizes surface glycoconjugates such as lipopolysaccharide, capsule, and capsule like complex for its protection against inhospitable conditions of the environment. Francisella species also possess a functional glycosylation apparatus by which specific proteins are O-glycosidically modified. We here created a mutant with a nonfunctional FTS_1402 gene encoding for a putative glycan flippase and studied the consequences of its disruption. The mutant strain expressed diminished glycosylation similarly to, but to a lesser extent than, that of the oligosaccharyltransferase-deficient DeltapglA mutant. In contrast to DeltapglA, inactivation of FTS_1402 had a pleiotropic effect, leading to alteration in glycosylation and, importantly, to decrease in lipopolysaccharide, capsule, and/or capsule-like complex production, which were reflected by distinct phenotypes in host-pathogen associated properties and virulence potential of the two mutant strains. Disruption of FTS_1402 resulted in enhanced sensitivity to complement-mediated lysis and reduced virulence in mice that was independent of diminished glycosylation. Importantly, the mutant strain induced a protective immune response against systemic challenge with homologous wild-type FSC200 strain. Targeted disruption of genes shared by multiple metabolic pathways may be considered a novel strategy for constructing effective live, attenuated vaccines. PMID- 26815359 TI - SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington's Disease Mice. AB - Huntington's disease (HD) is a neurodegenerative disorder for which there are no disease-modifying treatments. SIRT1 is a NAD+-dependent protein deacetylase that is implicated in maintaining neuronal health during development, differentiation and ageing. Previous studies suggested that the modulation of SIRT1 activity is neuroprotective in HD mouse models, however, the mechanisms controlling SIRT1 activity are unknown. We have identified a striatum-specific phosphorylation dependent regulatory mechanism of SIRT1 induction under normal physiological conditions, which is impaired in HD. We demonstrate that SIRT1 activity is down regulated in the brains of two complementary HD mouse models, which correlated with altered SIRT1 phosphorylation levels. This SIRT1 impairment could not be rescued by the ablation of DBC1, a negative regulator of SIRT1, but was linked to changes in the sub-cellular distribution of AMPK-alpha1, a positive regulator of SIRT1 function. This work provides insights into the regulation of SIRT1 activity with the potential for the development of novel therapeutic strategies. PMID- 26815360 TI - Separate and joint effects of alcohol and caffeine on conflict monitoring and adaptation. AB - RATIONALE: Caffeine is commonly believed to offset the acute effects of alcohol, but some evidence suggests that cognitive processes remain impaired when caffeine and alcohol are coadministered. OBJECTIVES: No previous study has investigated the separate and joint effects of alcohol and caffeine on conflict monitoring and adaptation, processes thought to be critical for self-regulation. This was the purpose of the current study. METHODS: Healthy, young adult social drinkers recruited from the community completed a flanker task after consuming one of four beverages in a 2 * 2 experimental design: Alcohol + caffeine, alcohol + placebo caffeine, placebo alcohol + caffeine, or placebo alcohol + placebo caffeine. Accuracy, response time, and the amplitude of the N2 component of the event related potential (ERP), a neural index of conflict monitoring, were examined as a function of whether or not conflict was present (i.e., whether or not flankers were compatible with the target) on both the previous trial and the current trial. RESULTS: Alcohol did not abolish conflict monitoring or adaptation. Caffeine eliminated conflict adaptation in sequential trials but also enhanced neural conflict monitoring. The combined effect of alcohol and caffeine was apparent only in how previous conflict affected the neural conflict monitoring response. CONCLUSIONS: Together, the findings suggest that caffeine leads to exaggeration of attentional resource utilization, which could provide short-term benefits but lead to problems conserving resources for when they are most needed. PMID- 26815361 TI - Acute stress increases ad-libitum alcohol consumption in heavy drinkers, but not through impaired inhibitory control. AB - RATIONALE: Stress increases alcohol consumption and the risk of relapse, but little is known about the psychological mechanisms that underlie these effects. One candidate mechanism is inhibitory control, which may be impaired by acute stress and is believed to exert a causal influence on alcohol consumption. OBJECTIVES: We investigated if acute stress would impair inhibitory control and if impaired inhibitory control would be associated with subsequent ad-libitum alcohol consumption in a naturalistic laboratory setting. MATERIALS AND METHODS: One hundred heavy drinkers took part in an experimental study in a naturalistic 'bar laboratory'. Participants were randomly assigned to an acute stress (n = 50) or control (n = 50) group. In the stress group, participants were exposed to the social evaluative threat of giving a self-critical presentation, whereas the control group completed simple anagrams. Prior to and following the manipulation, participants completed the stop signal task as a measure of inhibitory control. Finally, participants completed a bogus taste test, as a measure of ad-libitum alcohol consumption. RESULTS: The stress manipulation had no effect on performance on the stop signal task. However, there was a small but significant increase in ad-libitum alcohol consumption in the acute stress group compared to that in the control group. CONCLUSIONS: Acute stress increased alcohol consumption in heavy drinkers, in a semi-naturalistic setting. However, this was not through the hypothesised mechanism of a transient impairment in inhibitory control. PMID- 26815363 TI - Nahal Ein Gev II, a Late Natufian Community at the Sea of Galilee. AB - The Natufian culture is of great importance as a starting point to investigate the dynamics of the transition to agriculture. Given its chronological position at the threshold of the Neolithic (ca. 12,000 years ago) and its geographic setting in the productive Jordan Valley, the site of Nahal Ein Gev II (NEG II) reveals aspects of the Late Natufian adaptations and its implications for the transition to agriculture. The size of the site, the thick archaeological deposits, invested architecture and multiple occupation sub-phases reveal a large, sedentary community at least on par with Early Natufian camps in the Mediterranean zone. Although the NEG II lithic tool kit completely lacks attributes typical of succeeding Pre Pottery Neolithic A (PPNA) assemblages, the artistic style is more closely related to the early PPNA world, despite clear roots in Early Natufian tradition. The site does not conform to current perceptions of the Late Natufians as a largely mobile population coping with reduced resource productivity caused by the Younger Dryas. Instead, the faunal and architectural data suggest that the sedentary populations of the Early Natufian did not revert back to a nomadic way of life in the Late Natufian in the Jordan Valley. NEG II encapsulates cultural characteristics typical of both Natufian and PPNA traditions and thus bridges the crossroads between Late Paleolithic foragers and Neolithic farmers. PMID- 26815362 TI - Chamber Specific Gene Expression Landscape of the Zebrafish Heart. AB - The organization of structure and function of cardiac chambers in vertebrates is defined by chamber-specific distinct gene expression. This peculiarity and uniqueness of the genetic signatures demonstrates functional resolution attributed to the different chambers of the heart. Altered expression of the cardiac chamber genes can lead to individual chamber related dysfunctions and disease patho-physiologies. Information on transcriptional repertoire of cardiac compartments is important to understand the spectrum of chamber specific anomalies. We have carried out a genome wide transcriptome profiling study of the three cardiac chambers in the zebrafish heart using RNA sequencing. We have captured the gene expression patterns of 13,396 protein coding genes in the three cardiac chambers-atrium, ventricle and bulbus arteriosus. Of these, 7,260 known protein coding genes are highly expressed (>=10 FPKM) in the zebrafish heart. Thus, this study represents nearly an all-inclusive information on the zebrafish cardiac transcriptome. In this study, a total of 96 differentially expressed genes across the three cardiac chambers in zebrafish were identified. The atrium, ventricle and bulbus arteriosus displayed 20, 32 and 44 uniquely expressing genes respectively. We validated the expression of predicted chamber-restricted genes using independent semi-quantitative and qualitative experimental techniques. In addition, we identified 23 putative novel protein coding genes that are specifically restricted to the ventricle and not in the atrium or bulbus arteriosus. In our knowledge, these 23 novel genes have either not been investigated in detail or are sparsely studied. The transcriptome identified in this study includes 68 differentially expressing zebrafish cardiac chamber genes that have a human ortholog. We also carried out spatiotemporal gene expression profiling of the 96 differentially expressed genes throughout the three cardiac chambers in 11 developmental stages and 6 tissue types of zebrafish. We hypothesize that clustering the differentially expressed genes with both known and unknown functions will deliver detailed insights on fundamental gene networks that are important for the development and specification of the cardiac chambers. It is also postulated that this transcriptome atlas will help utilize zebrafish in a better way as a model for studying cardiac development and to explore functional role of gene networks in cardiac disease pathogenesis. PMID- 26815364 TI - Velocity of density shifts in Finnish landbird species depends on their migration ecology and body mass. AB - A multitude of studies confirm that species have changed their distribution ranges towards higher elevations and towards the poles, as has been predicted by climate change forecasts. However, there is large interspecific variation in the velocity of range shifts. From a conservation perspective, it is important to understand which factors explain variation in the speed and the extent of range shifts, as these might be related to the species' extinction risk. Here, we study shifts in the mean latitude of occurrence, as weighted by population density, in different groups of landbirds using 40 years of line transect data from Finland. Our results show that the velocity of such density shifts differed among migration strategies and increased with decreasing body size of species, while breeding habitat had no influence. The slower velocity of large species could be related to their longer generation time and lower per capita reproduction that can decrease the dispersal ability compared to smaller species. In contrast to some earlier studies of range margin shifts, resident birds and partial migrants showed faster range shifts, while fully migratory species were moving more slowly. The results suggest that migratory species, especially long-distance migrants, which often show decreasing population trends, might also have problems in adjusting their distribution ranges to keep pace with global warming. PMID- 26815365 TI - Intraspecific competitive ability declines towards the edge of the expanding range of the invasive vine Mikania micrantha. AB - The evolution of competitive ability plays an important role in plant invasions. While many studies of the evolution of invasive species have compared populations from native and invaded ranges in terms of their performance, little attention has been paid to the evolution of intraspecific competitive ability within the invaded range during range expansion. In addition, whether the proportional change in the amount of invasive litter influences the intraspecific competitive ability among invasive populations of different ages has not yet been investigated. Here we selected Mikania micrantha H.B.K., a highly invasive vine in south China with a well-documented invasion history, as the study species. We manipulated competition among populations of different ages from the core of the range to its edges under four litter treatments in a common garden experiment. We found that during its 30-year invasion, intraspecific competitive ability was rapidly selected against towards range edges, which may be driven partly by the decline in population density. However, litter source did not influence the outcome of the competition among populations of different ages; it instead functioned more like a supply of nutrients. We suggest that stage-specific conditions such as population density should be incorporated into the experimental design when examining the evolution of invasive plants, especially when invasive populations are subject to selection on a small geographic scale. This approach can reduce sampling bias and thus improve the ability to infer the mechanisms responsible for the evolution of invasive populations. PMID- 26815366 TI - A tale of two communities: Neotropical butterfly assemblages show higher beta diversity in the canopy compared to the understory. AB - Tropical fruit-feeding nymphalid butterflies generally restrict adult foraging exclusively to either the canopy or understory strata. We compared canopy and understory butterfly communities using data from four long-term studies in Central and South America. At all study sites we found little similarity in species composition between canopy and understory, with most species showing a strong affinity for one of the two habitats. There was a consistent phylogenetic signal for canopy and understory association, suggesting a substantial evolutionary history with these habitats. In addition to compositional differences, we found different patterns of beta diversity between canopy and understory communities. Across all study sites, the canopy had greater temporal and spatial beta diversity compared to the understory. Although these two communities are composed of the same feeding guild and separated only by a relatively small vertical space, each has its own stratum-specific species composition and community dynamics. PMID- 26815367 TI - Influence of MX1 promoter rs2071430 G/T polymorphism on susceptibility to systemic lupus erythematosus. AB - The expression of interferon inducible genes are reported to be heightened in systemic lupus erythematosus (SLE); nevertheless, not much is known regarding the genetic variants underlying these genes and their role in the pathogenesis of disease. Herein, we aim to explore the potential association and contribution of polymorphisms in MX1 gene (i) promoter with part of exon 1 (ii) intron 6, and (iii) their resulting haplotypes, with susceptibility to SLE. A total of 306 subjects, 152 SLE and 154 healthy controls (HC), were screened by direct sequencing method. Statistical analysis was carried out using appropriate software. The screening region of interest in MX1 revealed the existence of promoter (-123C/A, -88G/T, -20 A/C) and intron 6 (+9862G/A, +10190G/A, +9901C/G, +9920C/A, +9959C/T, +10047A/G) variants in SLE and HC. A significant association was observed between MX1 -88G/T SNP and susceptibility to SLE (chi (2) = 4.18, p = 0.04, OR = 1.89, 95 % CI 1.03-3.5). Haplotype analysis also revealed increased risk of SLE among individuals carrying CTA haplotype (-123 C, -88 T, -20 A) (chi (2) = 5.74, p = 0.017, OR = 4.28, 95 % CI 1.30-14.06). None of the other tested variants showed any significant association with SLE. The present study is the first to reveal the influence of genetic variation in MX1 gene in susceptibility to SLE. PMID- 26815368 TI - Comparison of shear wave velocities on ultrasound elastography between different machines, transducers, and acquisition depths: a phantom study. AB - OBJECTIVES: To investigate consistency in shear wave velocities (SWVs) on ultrasound elastography using different machines, transducers and acquisition depths. METHODS: The SWVs were measured using an elasticity phantom with a Young's modulus of 16.9 kPa, with three recently introduced ultrasound elastography machines (A, B and C from different vendors) and two transducers (low and high frequencies) at four depths (2, 3, 4 and 5 cm). Mean SWVs from 15 measurements and coefficient of variations (CVs) were compared between three machines, two transducers and four acquisition depths. RESULTS: The SWVs using the high frequency transducer were not acquired at 5 cm depth in machine B, and a high frequency transducer was not available in machine C. The mean SWVs in the three machines were different (p <= 0.002). The CVs were 0-0.09 in three machines. The mean SWVs between the two transducers were different (p < 0.001) except at 4 and 5 cm depths in machine A. The SWVs were affected by the acquisition depths in all conditions (p < 0.001). CONCLUSION: There is considerable difference in SWVs on ultrasound elastography depending on different machines, transducers and acquisition depths. Caution is needed when using the cutoff values of SWVs in different conditions. KEY POINTS: * The shear wave velocities (SWVs) are different between different ultrasound elastography machines * The SWVs are also different between different transducers and acquisition depths * Caution is needed when using the cutoff SWVs measured under different conditions. PMID- 26815369 TI - Endovascular management of delayed post-pancreatectomy haemorrhage. AB - OBJECTIVES: To assess the patient outcome after endovascular treatment of delayed post-pancreatectomy haemorrhage (PPH) as first-line treatment. METHODS: Between January 2005 and November 2013, all consecutive patients referred for endovascular treatment of PPH were included. Active bleeding, pseudoaneurysms, collections and the involved artery were recorded on pretreatment CT. Endovascular procedures were classified as technical success (source of bleeding identified on angiogram and treated), technical failure (source of bleeding identified but incompletely treated) and abstention (no abnormality identified, no treatment performed). Factors associated with rebleeding were analysed. RESULTS: Sixty-nine patients (53 men) were included (mean 59 years old (32-75)). Pretreatment CT showed 27 (39 %) active bleeding. In 22 (32 %) cases, no involved artery was identified. Technical success, failure and abstention were observed in 48 (70 %), 9 (13 %) and 12 patients (17 %), respectively. Thirty patients (43 %) experienced rebleeding. Rebleeding rates were 29 %, 58 % and 100 % in case of success, abstention and failure (p < 0.001). Treatment failure/abstention was the only factor associated with rebleeding. Overall, 74 % of the patients were successfully treated by endovascular procedure(s) alone. CONCLUSION: After a first endovascular procedure for PPH, the rebleeding rate is high and depends upon the success of the procedure. Most patients are successfully treated by endovascular approach(es) alone. KEY POINTS: * After a first endovascular procedure for PPH the rebleeding rate is high * The rebleeding rate is significantly associated with initial technical success * Three-quarters of the patients are successfully treated by endovascular procedure(s) alone. PMID- 26815372 TI - Focus on Distal Tibial Fractures. PMID- 26815371 TI - Combined effects of simulated acid rain and lanthanum chloride on chloroplast structure and functional elements in rice. AB - Acid rain and rare earth element (REE) pollution exist simultaneously in many agricultural regions. However, how REE pollution and acid rain affect plant growth in combination remains largely unknown. In this study, the combined effects of simulated acid rain and lanthanum chloride (LaCl3) on chloroplast morphology, chloroplast ultrastructure, functional element contents, chlorophyll content, and the net photosynthetic rate (P n) in rice (Oryza sativa) were investigated by simulating acid rain and rare earth pollution. Under the combined treatment of simulated acid rain at pH 4.5 and 0.08 mM LaCl3, the chloroplast membrane was smooth, proteins on this membrane were uniform, chloroplast structure was integrated, and the thylakoids were orderly arranged, and simulated acid rain and LaCl3 exhibited a mild antagonistic effect; the Mg, Ca, Mn contents, the chlorophyll content, and the P n increased under this combined treatment, with a synergistic effect of simulated acid rain and LaCl3. Under other combined treatments of simulated acid rain and LaCl3, the chloroplast membrane surface was uneven, a clear "hole" was observed on the surface of chloroplasts, and the thylakoids were dissolved and loose; and the P n and contents of functional elements (P, Mg, K, Ca, Mn, Fe, Ni, Cu, Zn and Mo) and chlorophyll decreased. Under these combined treatments, simulated acid rain and LaCl3 exhibited a synergistic effect. Based on the above results, a model of the combined effects of simulated acid rain and LaCl3 on plant photosynthesis was established in order to reveal the combined effects on plant photosynthesis, especially on the photosynthetic organelle-chloroplast. Our results would provide some references for further understanding the mechanism of the combined effects of simulated acid rain and LaCl3 on plant photosynthesis. PMID- 26815370 TI - Isoattenuating insulinomas at biphasic contrast-enhanced CT: frequency, clinicopathologic features and perfusion characteristics. AB - OBJECTIVES: We aimed to determine the frequency of isoattenuating insulinomas, to investigate their clinicopathological features and to assess their regional pancreatic perfusion characteristics. METHODS: Institutional review board approval was obtained, and patient informed consent was waived. From July 2010 to June 2014, 170 patients (66 male, 104 female) with endogenous hyperinsulinemic hypoglycemia underwent biphasic contrast-enhanced CT before surgery, and 129 of those patients also received preoperative whole-pancreas CT perfusion. A total of 181 tumours were proved histopathologically after surgery. Enhancement pattern and regional pancreatic perfusion characteristics were analyzed. Clinical features, tumour size and pathological grading were investigated. RESULTS: The frequency of isoattenuating tumours was 24.9 %. Tumour size and WHO grading was not significantly different between isoattenuating and hyperattenuating tumours. Tumour-free regions had identical blood flow (BF) regardless of their location (p = 0.35). Isoattenuating tumour-harbouring regions had lower BF compared with hyperattenuating tumour-harbouring regions; both showed higher BF compared with tumour-free neighbourhood regions (all p < 0.01). For patients with isoattenuating tumours, the overall hospital stay was longer (p < 0.01). CONCLUSIONS: A substantial subset of insulinomas were isoattenuating on biphasic CT. CT perfusion showed higher BF in tumour-harbouring regions compared to tumour free regions, providing a clue for tumour regionalization. KEY POINTS: * About a quarter of all insulinomas were isoattenuating on biphasic contrast-enhanced CT. * CT perfusion finds tumour-harbouring regions have higher blood-flow compared to tumour-free regions. * CT perfusion provides important information for tumour regionalization, for isoattenuating tumours. PMID- 26815373 TI - Treatment of Distal Lower Leg Fractures: Results with Fixed-Angle Plate Osteosynthesis. AB - Twenty-five patients with closed distal tibial fractures were treated with a fixed-angle (locked) plate osteosynthesis. The study period was from 1.1.06 to 31.12.07. According to AO classification, there were three A1, eight A2, nine A3, one B2, two C1, and two C3 fractures. All patients had a follow up examination after an average of 16.6 months. Complications included a technical mistake (fixation in slight malangulation), two infections, and one non union that showed consolidation after 15 months. All other patients reached bone consolidation and full weight bearing after an average of 3.5 months. The ankle range of motion for all patients was, on average, flexion/extension 18 degrees /35 degrees , without restrictions on the walking distance. No loss of reduction occurred. Fixed-angle plate osteosynthesis is a good alternative to intramedullary nailing when treating closed distal lower leg fractures. It is a demanding surgical method with good clinical and functional results. PMID- 26815374 TI - Distal Tibial Fractures: Intramedullary Nailing. AB - The tibia is an exposed bone with vulnerable soft tissue coverage and is therefore predisposed to local soft tissue problems and delayed bone healing. The objective in distal tibial fracture treatment is to achieve stable fixation patterns with a minimum of soft-tissue affection. Thus, the risk of soft tissue breakdown and bone healing complications is more likely related to open reduction and plating. Percutaneous, minimally invasive intramedullary nailing is a proven fixation mode for fracture stabilization in tibial shaft fractures. Anticipating the pitfalls, intramedullary nailing meets the requirements of the method of choice in distal tibial fracture fixation. In conclusion, intramedullary nailing of distal tibial fractures is a reliable method of fixation, possessing the advantages of closed reduction and symmetric fracture stabilization of an area with a delicate soft tissue situation, but prospective randomized trials are needed to compare modern intramedullary fracture fixation with modern plate fixation in distal tibial fractures. PMID- 26815375 TI - Operative Treatment and Soft Tissue Management of Open Distal Tibial Fractures - Pitfalls and Results. AB - Open tibial fractures usually result from high-energy trauma. Severe soft-tissue injuries are often combined with open fractures of the distal tibia. A consecutive series of 42 patients with open extraarticular distal tibial fractures (Gustilo I-IIIc) operated on between July 2006 and February 2009 were included in the study reported here. We performed open reduction and internal fixation for the Gustilo I cases. Soft tissue was closed directly after antibiotic beads had been temporarily applied. For the Gustilo II and III cases, our treatment protocol included soft-tissue debridement of all devitalized soft tissue and bone fragments, pulsatile jet irrigation, and external stabilization. Soft tissue was temporarily closed with Epigard_ after the application of antibiotic beads. A second-look operation was scheduled after 3-5 days. Gustilo II patients needed an average of 1.1 (0-3) revisions until wound closure, compared to the average of 2.1 revisions necessary for the Gustilo III patients. It took 5.6 (0-16) days to obtain definitive wound closure in the Gustilo II patients and 9.9 (3-28) days in the Gustilo III patients. Skin grafting was sufficient for definitive softtissue closure in ten cases, local flaps in eight cases, and free musculocutaneous flaps were needed in six cases. Gustilo II patients with primary wound closure remained hospitalized for 11 days, while patients with secondary wound closure stayed in hospital for an average of 20 days. Our early results concerning infection rate, number of reoperations, and time to bony consolidation can be compared with other studies. Functional results will have to be evaluated at clinical follow-up. PMID- 26815376 TI - A Single-Lumen Central Venous Catheter for Continuous and Direct Intra-abdominal Pressure Measurement. AB - BACKGROUND: Abdominal compartment syndrome (ACS) is associated with high morbidity and mortality rates. Therefore, the need for a good diagnostic tool to predict intra-abdominal hypertension (IAH) and progression to ACS is paramount. Bladder pressure (BP) has been used for several years for intra-abdominal pressure (IAP) measurement but has the disadvantage that it is not a continuous measurement. In this study, a single-lumen central venous catheter (CVC) is placed through the abdominal wall into the abdominal cavity to continuously and directly monitor the intraabdominal pressure (CDIAP). The aim of this study was to evaluate the use of CDIAP to measure BP as a representative of the true IAP. METHODS: Both BP and CDIAP were prospectively recorded on a variety of surgical patients admitted to the intensive care unit (ICU) from March 2003 up to December 2004. At the end of the surgical procedure, the CVC was placed through the abdominal wall and connected to a pressure transducer. In addition, the BP was measured through the urine drainage port after clamping the catheter and filling the bladder with 50 ml of 0.9% saline. At least three paired measurements (BP and CDIAP) were performed for at least one day on the ICU in a standardized manner at preset time intervals on each patient. The paired measurements were compared using the Bland-Altman (B-A) method. Data are presented as mean +/- standard deviation. RESULTS: Over a period of 22 months (March 2003 until December 2004), 125 paired measurements of both BP and CDIAP were recorded on 25 patients. The mean age was 72.4 +/- 6.6 years. Eighteen patients underwent central vascular surgery, and seven patients with peritonitis received laparotomy. The mean CDIAP was 11.4 +/- 4.8 (range 2-30) mmHg, and the BP was 12.9 +/- 5.3 (range 3-37) mmHg. The mean difference between CDIAP and BP was 1.6 +/- 2.7 mmHg. There was an acceptable level of agreement (intraclass correlation 0.82) between IAP measured by BP and IAP measured via CDIAP. CONCLUSION: Continuous direct intra-abdominal pressure measurement proved that the BP measurement approach of Kron is representative of the IAP. CDIAP measurement is accurate and makes it easier for the nursing staff to be informed of the IAP. PMID- 26815377 TI - The Severity of Injury and the Extent of Hemorrhagic Shock Predict the Incidence of Infectious Complications in Trauma Patients. AB - BACKGROUND: Trauma patients are at high risk of developing systemic inflammatory response syndrome (SIRS) and infections. The aim of this study was to evaluate the influence of the severity of injury and the extent of hemorrhagic shock at admission on the incidence of SIRS, infection and septic complications. METHODS: A total of 972 patients who had an injury severity score (ISS) of >= 17, survived more than 72 h, and were admitted to a level I trauma center within 24 h after trauma were included in this retrospective analysis. SIRS, sepsis and infection rates were measured in patientswith different severities of injury as assessed by ISS, or with various degrees of hemorrhagic shock according to ATLS((r)) guidelines, andwere compared using both uni- and multivariate analysis. RESULTS: Infection rates and septic complications increase significantly (p < 0.001) with higher ISS. Severe hemorrhagic shock on admission is associated with a higher rate of infection (72.8%) and septic complications (43.2%) compared to mild hemorrhagic shock (43.4%, p < 0.001 and 21.7%, p < 0.001, respectively). CONCLUSION: The severity of injury and the severity of hemorrhagic shock are risk factors for infectious and septic complications. Early diagnostic and adequate therapeutic work up with planned early "second look" interventions in such high risk patients may help to reduce these common posttraumatic complications. PMID- 26815378 TI - Relaparotomies: Why is Mortality Higher? AB - BACKGROUND: Relaparotomy is sometimes required for complications that develop after abdominal surgery, but it is associated with high mortality. We aimed to investigate the independent risk factors related to mortality in patients that undergo relaparotomies. MATERIALS AND METHODS: One hundred and fourteen patients who had relaparatomies were evaluated. Risk factors studied were patient characteristics, cause of the first operation, condition of the first operation, systemic diseases, presence of peritonitis, relaparotomy interval, cause of relaparatomy, APACHE II score, transfused blood units, number of relaparatomies, length of hospital stay, and mortality. In order to determine the independent risk factors, we carried out multivariate logistic regression analysis. RESULTS: There were 75 male and 39 female patients with a mean age of 46.06 +/- 19.98 (15 84). The most common reasons for relaparotomy were leakage from intestinal primary repair or anastomosis (29.8%). Mortality developed in 55 (48.2%) patients undergoing relaparatomy. Intestinal necrosis (p = 0038) and intraabdominal sepsis (p = 0.027) were found to be risk factors in mortality. In multivariate logistic regression analysis, advanced age (OR 0.966, p = 0. 0.017) and APACHE II score >= 20 (OR 0.137, p < 0.0001) were found to be independent risk factors affecting mortality. CONCLUSION: Advanced age and APACHE II score >= 20 were found to be independent risk factors affecting relaparotomy-related mortality. PMID- 26815379 TI - Effect of Intramedullary Nails in Tibial Shaft Fractures as a Factor in Raised Intracompartmental Pressures: a Clinical Study. AB - BACKGROUND: Tibial shaft fractures are the commonest cause of compartment syndrome. Intramedullary nails have been the most common treatment for such fractures. Raised pressures after nailing do not necessarily imply compartment syndrome, but are an important factor to consider when deciding on the appropriate treatment. METHODS: A clinical study was performed that included 80 cases diagnosed with tibial shaft fractures and treated with reamed intramedullary nails. Compartment pressure was measured with a slit catheter. The pressure was calculated before and just after surgery. Delta P values were also calculated. Patients with overpressure but no clinical suspicion of compartment syndrome were monitored for 24 h. Patients diagnosed with compartment syndrome were treated via fasciotomy. A descriptive and statistical study was performed with 95% confidence intervals and significant difference p < 0.05. RESULTS: A statistically significant increase in pressure was observed after surgery. Delta P values only decreased after nailing in the anterior compartment, although the decrease was not significant (p >= 0.05). Four cases required monitoring for 24 h. Eleven patients were diagnosed with compartment syndrome after surgery, with absolute pressures of over 30 mmHg and delta P values of less than 40 mmHg. CONCLUSIONS: Reamed intramedullary nails can increase compartment pressures in tibial shaft fractures. The delta P value can influence the decision about whether to perform a fasciotomy. The diagnosis of compartment syndrome must be based on clinical findings. If there is any doubt, we recommend measuring the pressure and using a cut-off value for fasciotomy of delta P <= 40 mmHg. A delay in definitive treatment is suggested until pressure values are secure. PMID- 26815381 TI - Esophageal Injury with Unusual Trauma. AB - Esophageal foreign bodies are frequently encountered in the pediatric population and specific high-risk groups of adults. Foreign bodies in the esophagus can result in serious complications, depending on the size and the shape of the ingested object. We report the case of a four-year-old boy with an esophageal injury after the accidental ingestion of an umbrella wire. PMID- 26815380 TI - Posterior Fusion in Patients with Trauma, Instability, and Tumor of the Cervical Spine. AB - Trauma, instabilities and tumors of the cervical spine are treated with established methods of surgery. Therefore, anterior fusion is considered to be a standardized procedure for the lower cervical spine, while posterior and anterior instrumentation facilitates stabilization of the upper cervical spine. However, special situations that particularly require posterior instrumentation in traumatic lesions, tumor or other kinds of instabilities arise again and again. Neurological deficit symptoms, bone quality and related diseases fundamentally lead to a decision of posterior access and fusion. Different pathologies and corresponding reasons for posterior surgical interventions on the cervical spine are described in this paper and discussed using the current literature. PMID- 26815382 TI - Post-traumatic Subserosal Small Bowel Herniation Leading to Obstruction in a Child with Acute Spinal Cord Injury. AB - The presentation of small bowel injury from lap belt use varies substantially, ranging from gross hemodynamic instability to insidious physiologic deterioration to simple failure of improvement. Rarely does small bowel injury manifest as an obstruction. This paper describes one such occurrence; in this case, herniation of intact mucosa/submucosa through a serosal tear caused a high-grade small bowel obstruction in a pediatric patient with an acute spinal cord injury and a virgin abdomen. PMID- 26815384 TI - Erratum to: Time for a Comprehensive Ultrasound-Enhanced Trauma Management. PMID- 26815383 TI - Management of Thyroid Gland Hemorrhage After Blunt Trauma: A Case Report and Review of the Literature. AB - BACKGROUND: Thyroid hemorrhage is a rare injury in patients suffering from blunt trauma to the neck. The case of a 60-year-oldwoman is describedwho developed increasing swelling in the neck with a mild inspiratory stridor after a fall from her bed. The fall had resulted in hemorrhage within a previously existing goiter. Further analysis by means of a CT scan revealed severe tracheal compression and active bleeding, which prompted immediate operative intervention. The patient recovered without complications. The decision-making process in this case is outlined, and other reports describing patients with thyroid hemorrhage after blunt cervical trauma are reviewed. CONCLUSION: Although blunt thyroid injury is an uncommon condition, failure to consider the diagnosis or failure to anticipate complications of thyroid hemorrhage may result in progressive bleeding and airway compromise. Decision making is based on the patient's vital signs and, if possible, the findings on a contrastenhanced CT scan of the neck. PMID- 26815385 TI - Fertilization and embryo quality of mature oocytes with specific morphological abnormalities. AB - OBJECTIVE: To investigate fertilization and embryo quality of dysmorphic mature oocytes with specific morphological abnormalities obtained from intracytoplasmic sperm injection (ICSI). METHODS: The fertilization rate (FR) and embryo quality were compared among 58 dysmorphic and 42 normal form oocytes (control 1) obtained from 35 consecutive ICSI cycles, each of which yielded at least one dysmorphic mature oocyte, performed over a period of 5 years. The FR and embryo quality of 441 normal form oocytes from another 119 ICSI cycles that did not involve dysmorphic oocytes served as control 2. Dysmorphic oocytes were classified as having a dark cytoplasm, cytoplasmic granularity, cytoplasmic vacuoles, refractile bodies in the cytoplasm, smooth endoplasmic reticulum in the cytoplasm, an oval shape, an abnormal zona pellucida, a large perivitelline space, debris in the perivitelline space, or an abnormal polar body (PB). RESULTS: The overall FR was significantly lower in dysmorphic oocytes than in normal form oocytes in both the control 1 and control 2 groups. However, embryo quality in the dysmorphic oocyte group and the normal form oocyte groups at day 3 was similar. The FR and embryo quality were similar in the oocyte groups with a single abnormality and multiple abnormalities. Specific abnormalities related with a higher percentage of top-quality embryos were dark cytoplasm (66.7%), abnormal PB (50%), and cytoplasmic vacuoles (25%). CONCLUSION: The fertilization potential of dysmorphic oocytes in our study was lower, but their subsequent embryonic development and embryo quality was relatively good. We were able to define several specific abnormalities related with good or poor embryo quality. PMID- 26815387 TI - Synthesis of 2,4,5-Trisubstituted Furans via a Triple C(sp(3))-H Functionalization Reaction Using Rongalite as the C1 Unit. AB - A highly efficient I2/Cu(NO3)2.3H2O-mediated triple C(sp(3))-H functionalization reaction for the synthesis of 2,4,5-trisubstituted furans from aryl methyl ketones and rongalite by employing rongalite as a C1 unit has been developed. This method allows rapid access to (2-acyl-4-methylthio-5-aryl) furans. Preliminary mechanistic studies indicate that in situ generated dimethyl(phenacyl)-sulfonium iodine and HCHO were probably the key intermediates in this transformation. PMID- 26815389 TI - Abstracts 1(st) Joint Congress, European Association for Trauma and Emergency Surgery-EATES and European Trauma Society-ETS May 23-26, 2007, Graz, Austria. PMID- 26815391 TI - Metal removal. PMID- 26815388 TI - Adaptable stirred-tank culture strategies for large scale production of multicellular spheroid-based tumor cell models. AB - Currently there is an effort toward the development of in vitro cancer models more predictive of clinical efficacy. The onset of advanced analytical tools and imaging technologies has increased the utilization of spheroids in the implementation of high throughput approaches in drug discovery. Agitation-based culture systems are commonly proposed as an alternative method for the production of tumor spheroids, despite the scarce experimental evidence found in the literature. In this study, we demonstrate the robustness and reliability of stirred-tank cultures for the scalable generation of 3D cancer models. We developed standardized protocols to a panel of tumor cell lines from different pathologies and attained efficient tumor cell aggregation by tuning hydrodynamic parameters. Large numbers of spheroids were obtained (typically 1000-1500 spheroids/mL) presenting features of native tumors, namely morphology, proliferation and hypoxia gradients, in a cell line-dependent mode. Heterotypic 3D cancer models, based on co-cultures of tumor cells and fibroblasts, were also established in the absence or presence of additional physical support from an alginate matrix, with maintenance of high cell viability. Altogether, we demonstrate that 3D tumor cell model production in stirred-tank culture systems is a robust and versatile approach, providing reproducible tools for drug screening and target verification in pre-clinical oncology research. PMID- 26815386 TI - Peptide- and Amine-Modified Glucan Particles for the Delivery of Therapeutic siRNA. AB - Translation of siRNA technology into the clinic is limited by the need for improved delivery systems that target specific cell types. Macrophages are particularly attractive targets for RNAi therapy because they promote pathogenic inflammatory responses in a number of important human diseases. We previously demonstrated that a multicomponent formulation of beta-1,3-d-glucan-encapsulated siRNA particles (GeRPs) can specifically and potently silence genes in mouse macrophages. A major advance would be to simplify the GeRP system by reducing the number of delivery components, thus enabling more facile manufacturing and future commercialization. Here we report the synthesis and evaluation of a simplified glucan-based particle (GP) capable of delivering siRNA in vivo to selectively silence macrophage genes. Covalent attachment of small-molecule amines and short peptides containing weak bases to GPs facilitated electrostatic interaction of the particles with siRNA and aided in the endosomal release of siRNA by the proton-sponge effect. Modified GPs were nontoxic and were efficiently internalized by macrophages in vitro. When injected intraperitoneally (i.p.), several of the new peptide-modified GPs were found to efficiently deliver siRNA to peritoneal macrophages in lean, healthy mice. In an animal model of obesity induced inflammation, i.p. administration of one of the peptide-modified GPs (GP EP14) bound to siRNA selectively reduced the expression of target inflammatory cytokines in the visceral adipose tissue macrophages. Decreasing adipose tissue inflammation resulted in an improvement of glucose metabolism in these metabolically challenged animals. Thus, modified GPs represent a promising new simplified system for the efficient delivery of therapeutic siRNAs specifically to phagocytic cells in vivo for modulation of inflammation responses. PMID- 26815392 TI - Indications for implant removal after fracture healing: a review of the literature. AB - INTRODUCTION: The aim of this review was to collect and summarize published data on the indications for implant removal after fracture healing, since these are not well defined and guidelines hardly exist. METHODS: A literature search was performed. RESULTS: Though there are several presumed benefits of implant removal, such as functional improvement and pain relief, the surgical procedure can be very challenging and may lead to complications or even worsening of the complaints. Research has focused on the safety of metal implants (e.g., risk of corrosion, allergy, and carcinogenesis). For these reasons, implants have been removed routinely for decades. Along with the introduction of titanium alloy implants, the need for implant removal became a subject of debate in view of potential (dis)advantages since, in general, implants made of titanium alloys are more difficult to remove. Currently, the main indications for removal from both the upper and lower extremity are mostly 'relative' and patient-driven, such as pain, prominent material, or simply the request for removal. True medical indications like infection or intra-articular material are minor reasons. CONCLUSION: This review illustrates the great variety of view points in the literature, with large differences in opinions and practices about the indications for implant removal after fracture healing. Since some studies have described asymptomatic patients developing complaints after removal, the general advice nowadays is to remove implants after fracture healing only in symptomatic patients and after a proper informed consent. Well-designed prospective studies on this subject are urgently needed in order to form guidelines based on scientific evidence. PMID- 26815394 TI - Implant removal in children. AB - PURPOSE: Implant removal in children is still a standard procedure. Implants may disturb function, and some theoretical long-term risks like growth disturbance, foreign body reaction, chronic infection and corrosion are used as arguments for removal. Implant migration or interference with any other orthopaedic treatment over the later course of life is also a matter of debate. On the other hand, the difficulty in removing single implants as well as possible perioperative complications has induced discussion about the retention of implants in childhood. METHODS: The current procedures are exposed and the available literature on implant removal in children reviewed. RESULTS: Actually, a clear recommendation does not exist. The current line of action still includes routine removal, as it is preferred by some authors, whereas others argue for a selective procedure. K-wires as well as intramedullary nails are usually removed because the ends may interfere with the surrounding tissue. Screws and plates can be retained if there are no local problems. The removal of external fixators is non controversial. CONCLUSIONS: Benefits have to outweigh the risks and complications in the individual case and the procedure should not require a more extensive procedure than insertion. It has to be an individual decision in view of the lack of evidence to support routine removal as well as to refute it. PMID- 26815393 TI - Technical complications during removal of locking screws from locking compression plates: a prospective multicenter study. AB - PURPOSE: To assess the risk for technical complications in patients undergoing removal of locking compression plates (LCP) with head locking screws. METHODS: A total of 205 patients who were scheduled for implant removal surgery after a healed fracture of the femur, tibia, humerus, distal radius, or clavicle in nine Austrian clinics were prospectively included in the study, all of whom had previously undergone fracture fixation by plates, with titanium implants used in 98 % of the patients. Intraoperative technical complications and the methods used to solve them were documented by the surgeon. RESULTS: During the course of this study, a total of 1,462 locking screws were removed from 204 LCPs. While 95 % of these screws could be removed without difficulties, technical complications were reported for 41 patients with 78 screws which could not be removed with standard screwdrivers and required the use of additional instruments. The estimated risk for the occurrence of at least one technical complication during implant removal surgery was 20.1 %. The most frequently observed complications were screws that could not be loosened because they were jammed in the LCP, screws with a damaged recess in which the screwdriver turned freely, as well as a combination of both events. The majority of these screws could be removed with the use of a conical extraction screw or by drilling off the screw head. In one patient, an intraoperative refracture of the humerus occurred during plate removal. Even though there is a rate of 20 % for technical complications when removing the implants, only a few patients experience a clinical impact. CONCLUSIONS: Titanium LCPs are prone to technical complications during implant removal, but the majority of the issues can be solved using special techniques. PMID- 26815395 TI - Pain and quality of life 1 year after admission to the emergency department: factors associated with pain. AB - OBJECTIVES: This study describes the prevalence of pain in trauma patients 1 year after hospital admission and investigates separately health-related quality of life (QoL) for patients suffering severe pain and for those without pain. Moreover, psychosocial factors are examined for their impact on pain. METHODS: Patients were contacted 12 months after admission in order to complete the following questionnaires: Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), Trauma Outcome Profile (TOP), Beck Depression Inventory (BDI), State Trait Anxiety Inventory (STAI), Impact of Event Scale-Revised (IES-R) and additional questions concerning satisfaction, work and financial status. Relevant pain at follow-up was defined as <80 points on the pain subscale of the TOP. RESULTS: Two hundred and twenty patients were included. The Injury Severity Score (ISS) ranged from 1 to 41. Fifty-three percent (53 %) of patients suffered a severe trauma (ISS > 15). One year after injury, 55 % of patients had relevant pain according to the TOP. Patients with pain were older (41.4 vs. 34.4 years, p = 0.003) and had slightly more severe injuries (ISS 17.1 vs. 14.9, p = 0.115). There were significant differences between pain and no-pain patients on all domains of QoL (p < 0.001) and on the BDI, STAI and IES-R (p < 0.001). Pain patients more often experienced a stressful event and job-related and financial difficulties. Multivariate logistic regression analysis revealed post-traumatic stress disorder (PTSD) as the strongest predictor for pain [odds ratio (OR): 4.38, p = 0.015], followed by a stressful life event (OR: 4.08, p = 0.001). DISCUSSION: Pain is strongly associated with psychosocial complaints 1 year after trauma. For the treatment of pain following a traumatic event, social reintegration and emotional regulation by means of occupational rehabilitation and psychotherapy should receive more attention. PMID- 26815396 TI - The influence of alcohol intoxication on the severity of injuries suffered by drivers in road traffic accidents. AB - PURPOSE: To determine the severity of injuries in drunk and sober drivers in traffic accidents, by using the Injury Severity Score (ISS), as well as the most vulnerable body region of those involved. METHODS: This was an observational case control study covering a 1-year period of patients treated in the emergency department of the Health Center in Kraljevo, Serbia. Seventy-five patients were identified as drunken drivers [blood alcohol concentration (BAC) >0.03 %] (group of cases), while 70 patients were found to be sober drivers (group of controls). Injuries were categorized by body region according to the ISS. RESULTS: Half of all drivers (51.7 %) injured in traffic accidents were under the influence of alcohol. Males represented a substantial majority of both groups. In both categories of drivers, the greatest incidence of traffic accidents was in the age group 19-35 years. Injuries of drunken drivers were more frequently present in all body regions except in the areas of limbs with shoulder and pelvic bones. Drivers under the influence of alcohol have a 3.80 times greater risk of suffering deadly injuries in traffic accidents. The average ISS in drunken drivers was higher in comparison to sober drivers (p < 0.05). The greatest ISS was in the drunk group with BAC level over 0.051 % (the ISS range was 15-20). A strong correlation was found between the BAC level and the degree of injury (r = 0.63). CONCLUSION: The severity of injuries and, especially, the 3.80 times greater risk of suffering deadly injuries in traffic accidents for drunken drivers obliges us to pay attention to prevention strategies. PMID- 26815397 TI - Epidemiology and management of trauma patients in a Greek multispecialty hospital in the absence of a dedicated trauma center. AB - PURPOSE: In the absence of dedicated trauma centers, surgical emergency departments in hospitals assigned as trauma centers accept a huge load of trauma patients. In this audit, we aim to document and assess the epidemiologic data of trauma patients and their injuries in order to give a picture of the impact of trauma in the workload of a surgical department in the Greek healthcare system. METHODS: During a period of 2 years, we managed 6,041 trauma patients in the accident and emergency (A&E) department based on the Advanced Trauma Life Support (ATLS) protocols. We retrospectively reviewed the emergency department registry and the admissions. RESULTS: 47.56 % of the patients seen in the A&E department were trauma patients. The mean age of the trauma patients was 44.52 years (range 15-106 years). The majority were men (60.4 %). The leading cause of trauma was motor and vehicle accidents, followed by slip and fall accidents, physical assault, fall from height, and vehicle pedestrian accidents. The majority of the patients were discharged from the hospital. Only 29 (4.6 %) out of 624 patients who were admitted to the general surgery department underwent an operation, while the rest were admitted for observation. On the other hand, patients were admitted to other departments only when surgical treatment was necessary. CONCLUSIONS: In the absence of level one trauma centers, in multispecialty urban hospitals, the coordination of trauma burdens the general surgery team. This has financial and administrative implications. The collection of important epidemiologic data from these hospitals is mandatory in order to develop national prevention measures against injuries. PMID- 26815398 TI - Cause of death and time of death distribution of trauma patients in a Level I trauma centre in the Netherlands. AB - OBJECTIVE: The classical trimodal distribution of trauma deaths describes three peaks of deaths following trauma: immediate, early and late deaths. The aim of this study was to evaluate whether further maturation of the trauma centre and the improvement of survival have had an effect on the time of death distribution and resulted in a shift in causes of death. METHODS: All trauma patients from 1999 to 2010 who died after arrival in the emergency room and prior to discharge from the hospital were included. Deaths caused by drowning, poisoning and overdose were excluded. RESULTS: A total of 16,421 trauma patients were admitted to our hospital. 772 (4.7 %) patients died, of which 720 were included in this study. The trauma mechanism was predominantly blunt (94.7 %). 530 patients (73.6 %) had Injury Severity Score (ISS) >=25. The most frequent causes of death were central nervous system (CNS) injury (59.9 %), exsanguinations (12.9 %) and pneumonia/respiratory insufficiency (8.5 %). The first peak of death was seen in the first hour after arrival at the emergency department; subsequently, a rapid decline was observed and no further peaks were seen. Over the years, we observed a general decrease in deaths due to exsanguination (p = 0.035) and a general increase in deaths due to CNS injury (p = 0.004). CONCLUSION: The temporal distribution of trauma deaths in our hospital changed as maturation of the trauma centre occurred. There is one peak of trauma deaths in the first hour after admission, followed by a rapid decline; no trimodal distribution was observed. Over time, there was a decrease in exsanguinations and an increase of deaths due to CNS injury. PMID- 26815399 TI - Influence of vagal injury on acute traumatic reaction after blast injury. AB - INTRODUCTION: A prospectively randomised, controlled animal study was conducted to analyse the influence of vagal injury on acute cardio-respiratory responses to blast injury. MATERIALS AND METHODS: We used a previously described model of blast-fragment combined injuries to divide dogs randomly into three groups: normal control, blast injury with fragment shot at the masseter and blast injury with fragment shot at the neck. The vagal histomorphologic changes were investigated by haematoxylin-eosin staining and immunocytochemical analysis of neuron-specific enolase and glial fibrillary acidic protein. The indices of respiration, heart rate, blood pressure and body temperature were recorded continuously before and after blast exposure. RESULTS: The vagal injury was more severe in the neck-injured than in the face-injured group. However, bradycardia, hypotension and absence of compensatory peripheral vasoconstriction, which are typically seen in animals subjected to blast injury without vagal nerve injuries, were partly inhibited when the vagal nerve was injured. CONCLUSION: A vagally mediated reflex, such as a cardio-respiratory system defensive reflex that caused shock, was observed immediately after blast pressure wave injury. These observations may have important implications for the emergency management of blast injury cases. PMID- 26815400 TI - Management of chronic traumatic arteriovenous fistula of the lower extremities. AB - INTRODUCTION: Vascular injuries secondary to blunt or penetrating trauma are a significant cause of morbidity and mortality, especially in war-afflicted areas. Due to the violent situations of Pakistan and the unavailability of vascular services in remote areas, we are witnessing an increase in the number of delayed/chronic post-traumatic arteriovenous fistulas (AVFs) of the extremities in our institution. The purpose of this study is to share our experience of post traumatic AVF and the incidence, presentation, and outcomes of these patients. METHODS: A 10-year retrospective study between January 2002 and May 2012 was conducted. We studied 30 patients with post-traumatic AVF of the lower limbs. RESULTS: All 30 cases were due to penetrating injuries, either by gun shots or bomb blasts. All of the patients were treated surgically, except for one patient who was treated with a covered stent. The interval between surgery and presentation ranged from 6 months to 20 years. All patients had complete obliteration of the fistulous tract and there was no recurrence and no post operative mortality. CONCLUSION: Long-standing traumatic AVF is becoming common in Pakistan. Surgery remains the standard treatment. PMID- 26815401 TI - Age and traumatic chest injury: a 3-year observational study. AB - BACKGROUND: A quarter of trauma-related deaths are attributable to traumatic chest injury (TCI). OBJECTIVE: To outline the pattern and outcome of TCI in a rapidly developing country among different age groups. METHODS: We conducted a retrospective observational study for patients who sustained TCI and admitted between January 2008 and December 2010 to the Level I trauma center at Hamad General Hospital in Qatar. Patients were classified and analyzed in four age groups (group 1 <=18, group 2 between 19-44, group 3 45-59, and group 4 >60 years). Multivariate regression analysis was performed for predictors of mortality. RESULTS: Of 5,118 cases admitted to the Section of Trauma Surgery, 1,355 (26.5 %) had TCI (12, 67, 16, and 5 % in groups 1-4, respectively), which was due to blunt trauma in 96 % of cases. The overall mean age was 33 +/- 15 years and males comprised 94 % of cases. Children (<=18 years of age) had more traffic-related injury, intubation, high Injury Severity Score (ISS) (19 +/- 12), and associated head and liver injuries in comparison to the other groups. The overall mortality rate was 13 % (24, 11, 12, and 16 % in groups 1-4, respectively). The death rate was higher in pedestrians, followed by motor vehicle crashes (MVCs) and fall-related injuries (24 vs. 13 vs. 7 %, respectively, p = 0.001). The highest mortality occurred within the first day (n = 115, 65 %). In comparison to old age, children were more likely to die early (on the first day) and the adult group died mostly within the first week of hospitalization. Independent predictors for mortality included associated head injury [odds ratio (OR) 2.3, 95 % confidence interval (CI) 1.48-3.62), ISS (OR 1.11, 95 % CI 1.09-1.13), and age (OR 0.37, 95 % CI 0.22-0.62). CONCLUSION: TCI is an alarming problem in Qatar, with a bimodal mortality curve. The highest mortality peak occurred in children, followed by old age. However, young males are the most exposed population. Regulatory efforts and strict enforcement of traffic laws would likely reduce morbidity and mortality. PMID- 26815403 TI - Elective spare parts free flap-calcaneal fillet of foot flap. AB - Severe lower limb trauma with significant soft tissue injury can be managed with reconstruction or, if this is impossible, amputation. If amputation is considered, below-knee amputation preserving limb length is optimal for long-term functional outcome. At times, soft tissue/bony injury can limit the ability to preserve limb length, particularly with proximal tibial injuries. We present a case of elective below-knee amputation where leg length and adequate soft tissue coverage was only possible by using an osteocutaneous fillet of foot and lower leg spare parts free flap, maintaining the tibial nerve pedicle for sensation and the posterior tibial artery for vascularity of the nerve. The procedure was technically challenging and required follow-up debulking operations. However, the technique provided the significant advantage of immediate sensation of robust glabrous distal stump cover and optimising leg length to enhance functional outcome. PMID- 26815404 TI - More on acetabular fractures: the Trojan War and the Roman Empire. PMID- 26815402 TI - Impact of fluid therapy on apoptosis and organ injury during haemorrhagic shock in an oxygen-debt-controlled pig model. AB - INTRODUCTION: Apoptosis, or programmed cell death, seems to play a role in the physiology of shock. The influence of fluid resuscitation on the occurrence of apoptosis during haemorrhage is still unclear. Using an experimental randomised study, the goal of this investigation was to find a relation between different frequently used resuscitation fluids and evidence of apoptosis. MATERIALS AND METHODS: Sixty female pigs with a mean body weight of 20 kg were randomised into six groups, each receiving a different resuscitation fluid therapy: malated Ringer, lactated Ringer, hypertonic saline, hypertonic saline solution/Dextran 60, carbonate/gelatine and a sham group (no shock, no resuscitation). A haemorrhagic shock with a predefined oxygen debt with high mortality expected was induced for a period of 60 min. Then, the resuscitation fluid therapy within each group was initiated. At the beginning, after 1 h of shock and 1 and 2 h after resuscitation, biopsies from the liver were taken, as one of the most important metabolism organs of shock. Three hours after the beginning of the resuscitation period, the animals were allowed to recover under observation for 3 days. At the end of this period, a state of narcosis was induced and another liver biopsy was taken. Finally, the animals were sacrificed and samples were taken from the liver, kidney, heart and hippocampus. The TUNEL method was used for identifying apoptosis. Impairment of liver function was indicated by the measurement of transaminase levels. RESULTS: There was no observed difference in the rate of apoptosis in all groups and a low number of apoptotic cells were found in all the organs sampled. The sham group also showed a low count of apoptosis. The hypoxia sensitive neurons within the hippocampus did not show any signs of apoptosis. The high oxygen debt during haemorrhage led to a high mortality. The non-treated animals died very quickly, as an indicator for severe shock. Animals treated with hypertonic saline showed a significant increase in aspartate transaminase (AST) plasma levels on the first day after shock. CONCLUSION: The different resuscitation fluids used in the treatment of haemorrhagic shock in this experimental model showed no evidence of a different apoptosis rate in the end organs. PMID- 26815405 TI - Estes News. PMID- 26815407 TI - Solubility and crystallographic facet tailoring of (GaN)(1-x)(ZnO)(x) pseudobinary solid-solution nanostructures as promising photocatalysts. AB - (GaN)1-x(ZnO)x solid-solution nanostructures with superior crystallinity, large surface areas and visible light absorption have been regarded as promising photocatalysts for overall water splitting to produce H2. In this work, we report the preparation of (GaN)1-x(ZnO)x solid-solution nanorods with a high ZnO solubility up to 95% via a two-step synthetic route, which starts from a sol-gel reaction and follows with a nitridation process. Moreover, we clearly demonstrated that the crystallographic facets of (GaN)1-x(ZnO)x solid-solution nanorods can be finely tailored from non-polar {1010} to semipolar {1011} and then finally to mixed {101} and polar {0001} by carefully controlling the growth temperature and nitridation time. Correspondingly, the ZnO content in the GaN lattice can be achieved in the range of ~25%-95%. Room-temperature cathodoluminescence (CL) measurements on the three types of (GaN)1-x(ZnO)x solid solution nanorods indicate that the minimum band-gap of 2.46 eV of the solid solution nanorods is achieved under a ZnO solubility of 25%. The efficiency and versatility of our strategy in the band-gap and facet engineering of (GaN)1 x(ZnO)x solid-solution nanorods will enhance their promising photocatalytic utilizations like an overall water splitting for H2 production under visible light irradiation. PMID- 26815408 TI - Reticular pseudodrusen characterization by retromode imaging. PMID- 26815406 TI - Antigen receptor-mediated depletion of FOXP3 in induced regulatory T-lymphocytes via PTPN2 and FOXO1. AB - Regulatory T-cells induced via IL-2 and TGFbeta in vitro (iTreg) suppress immune cells and are potential therapeutics during autoimmunity. However, several reports described their re-differentiation into pathogenic cells in vivo and loss of their key functional transcription factor (TF) FOXP3 after T-cell antigen receptor (TCR)-signalling in vitro. Here, we show that TCR-activation antagonizes two necessary TFs for foxp3 gene transcription, which are themselves regulated by phosphorylation. Although the tyrosine phosphatase PTPN2 is induced to restrain IL-2-mediated phosphorylation of the TF STAT5, expression of the TF FOXO1 is downregulated and miR-182, a suppressor of FOXO1 expression, is upregulated. TGFbeta counteracts the FOXP3-depleting TCR-signal by reassuring FOXO1 expression and by re-licensing STAT5 phosphorylation. Overexpressed phosphorylation independent active versions of FOXO1 and STAT5 or knockdown of PTPN2 restores FOXP3 expression despite TCR-signal and absence of TGFbeta. This study suggests novel targets for stabilisation and less dangerous application of iTreg during devastating inflammation. PMID- 26815409 TI - Binding Site Identification and Flexible Docking of Single Stranded RNA to Proteins Using a Fragment-Based Approach. AB - Protein-RNA docking is hampered by the high flexibility of RNA, and particularly single-stranded RNA (ssRNA). Yet, ssRNA regions typically carry the specificity of protein recognition. The lack of methodology for modeling such regions limits the accuracy of current protein-RNA docking methods. We developed a fragment based approach to model protein-bound ssRNA, based on the structure of the protein and the sequence of the RNA, without any prior knowledge of the RNA binding site or the RNA structure. The conformational diversity of each fragment is sampled by an exhaustive RNA fragment library that was created from all the existing experimental structures of protein-ssRNA complexes. A systematic and detailed analysis of fragment-based ssRNA docking was performed which constitutes a proof-of-principle for the fragment-based approach. The method was tested on two 8-homo-nucleotide ssRNA-protein complexes and was able to identify the binding site on the protein within 10 A. Moreover, a structure of each bound ssRNA could be generated in close agreement with the crystal structure with a mean deviation of ~1.5 A except for a terminal nucleotide. This is the first time a bound ssRNA could be modeled from sequence with high precision. PMID- 26815410 TI - Improving Appropriate Access to Care With Central Referral and Triage in Rheumatology. AB - OBJECTIVE: To evaluate the short-term and long-term impact of a centralized system for the intake and triage of rheumatology referrals on access to care and referral quality. METHODS: An innovative central referral process, the Central Referral and Triage in Rheumatology (CReATe Rheum) program, was implemented in 2006, serving a referral base of 2 million people. Referrals are received in a central office, triaged by trained nurses, and assigned to the next available appointment on a prioritized basis. To evaluate the short-term impact, we compared wait times, duplicate referrals, and no-shows from a pre-implementation practice audit to a 2-year post-implementation evaluation (January 2007 to December 2008). Rheumatologists also assessed the quality and completeness of the referral information and accuracy of the urgency category assigned during triage. We evaluated the long-term impact by tracking referral volume, wait times, and rheumatologist manpower each year until December, 2013. RESULTS: During the first 2 years, wait-time variability between rheumatologists decreased, and wait times were reduced for moderate and urgent referrals. CReATe Rheum improved the quality of referral information and eliminated duplicate referrals. The urgency of the referral was assigned correctly in 90% of referrals. Over the long term, CReATe Rheum maintained short wait times for more urgent patients despite a growing number of referrals and a stable number of rheumatologists. CONCLUSION: A centralized system for the intake and triage of rheumatology referrals improved referral quality, reduced system inefficiencies, and effectively managed wait times on a prioritized basis for a large referral population. PMID- 26815412 TI - Series on vascular injuries: complex injuries and difficult problems. Surgical strategies for their management : Editors: Dr. Juan A. Asensio, University of Miami, Miami, Florida Dr. David V. Feliciano, Emory University, Atlanta, Georgia Dr. Donald D. Trunkey, University of Oregon, Portland, Oregon Dr. Ari Leppaniemi, Helsinki University, Helsinki, Finland. PMID- 26815413 TI - Penetrating carotid artery: uncommon complex and lethal injuries. AB - Carotid arterial injuries are the most difficult and certainly the most immediately life-threatening injuries found in penetrating neck trauma. Their propensity to bleed actively and potentially occludes the airway and makes surgical intervention very challenging. Their potential for causing fatal neurological outcomes demands that trauma surgeons exercise excellent judgment in the approach to their definitive management. The purpose of this article is to review the diagnosis and management of these injuries. PMID- 26815411 TI - Critical Role of Glucose Metabolism in Rheumatoid Arthritis Fibroblast-like Synoviocytes. AB - OBJECTIVE: Up-regulation of glucose metabolism has been implicated not only in tumor cell growth but also in immune cells upon activation. However, little is known about the metabolite profile in rheumatoid arthritis (RA), particularly in fibroblast-like synoviocytes (FLS). This study was undertaken to evaluate whether changes in glucose metabolism in RA FLS could play a role in inflammation and joint damage. METHODS: Synovium and FLS were obtained from patients with RA and patients with osteoarthritis (OA). The rate of glycolysis after stimulation of FLS with lipopolysaccharide and platelet-derived growth factor BB was measured using glycolysis stress test technology. FLS function was evaluated using a glycolysis inhibitor, 2-deoxy-d-glucose (2-DG). After stimulation of the FLS, a migration scratch assay, MTT assay, and enzyme-linked immunosorbent assay were performed to measure the effect of 2-DG on FLS migration, viability of the FLS, and cytokine secretion, respectively. IRDye 800CW 2-DG was used to assess glucose uptake in the arthritic joints and stromal cells of mice after K/BxN mouse serum transfer. The mice were injected daily, intraperitoneally, with 3-bromopyruvate (BrPa; 5 mg/kg) to assess the effect of inhibition of glycolysis in vivo. RESULTS: Compared to human OA FLS, the balance between glycolysis and oxidative phosphorylation was shifted toward glycolysis in RA FLS. Glucose transporter 1 (GLUT1) messenger RNA (mRNA) expression correlated with baseline functions of the RA FLS. Glucose deprivation or incubation of the FLS with glycolytic inhibitors impaired cytokine secretion and decreased the rate of proliferation and migration of the cells. In a mouse model of inflammatory arthritis, GLUT1 mRNA expression in the synovial lining cells was observed, and increased levels of glucose uptake and glycolytic gene expression were detected in the stromal compartment of the arthritic mouse joints. Inhibition of glycolysis by BrPa, administered in vivo, significantly decreased the severity of arthritis in this mouse model. CONCLUSION: Targeting metabolic pathways is a novel approach to understanding the mechanisms of disease. Inhibition of glycolysis may directly modulate synoviocyte mediated inflammatory functions and could be an effective treatment strategy for arthritis. PMID- 26815414 TI - Subclavian vessel injuries: difficult anatomy and difficult territory. AB - INTRODUCTION: Thoracic and thoracic related vascular injuries represent complex challenges to the trauma surgeon. Subclavian vessel injuries, in particular, are uncommon and highly lethal. Regardless of the mechanism, such injuries can result in significant morbidity and mortality. MATERIALS AND METHODS: Systematic review of the literature, with emphasis on the diagnosis, treatment and outcomes of these injuries, incorporating the authors' experience. CONCLUSIONS: These injuries are associated with significant morbidity and mortality. Patients who survive transport are subject to potentially debilitating injury and possibly death. Management of these injuries varies, depending on hemodynamic stability, mechanism of injury, and associated injuries. Despite significant advancements, mortality due to subclavian vessel injury remains high. PMID- 26815415 TI - Operative exposure and management of axillary vessel injuries. AB - INTRODUCTION: Axillary vessel injuries are uncommon and challenging injuries encountered by trauma surgeons. Proximity of this vessel to other adjacent veins including the axillary vein, brachial plexus and the osseous structures of the shoulder and upper arm account for a large number of associated injuries. MATERIALS AND METHODS: Systematic review of the literature, with emphasis on the diagnosis, treatment and outcomes of these injuries, incorporating the authors' experience. CONCLUSIONS: Although uncommon, axillary arterial injuries can result in significant morbidity, limb loss and mortality. Early diagnosis and timely repair of the artery leads to good outcomes. PMID- 26815416 TI - Brachial vessel injuries: high morbidity and low mortality injuries. AB - INTRODUCTION: Reports of arterial injuries from both the civilian and military arenas report the brachial artery as the most frequently injured vessel, accounting for approximately 25-33% of all peripheral arterial injuries. The brachial artery is surrounded by important peripheral nerves -the median, ulnar and radial, and also parallels the humerus and associated veins. Due to its close proximity to these structures, associated nerve and osseous injuries are frequent with residual neuropathy from such nerve injuries, often the main sources of permanent disability. MATERIALS AND METHODS: Systematic review of the literature, with emphasis in the diagnosis, treatment and outcomes of these injuries, incorporating the authors experience. CONCLUSIONS: The morbidity and mortality rates associated with brachial artery injuries depend on the cause of the injury itself, which vein or tendon is injured, and whether musculoskeletal and nerve injuries are also present. During the last 20 years, amputation associated with upper extremity arterial injuries has decreased to a rate of 3% because of advances in the treatment of shock, the use of antibiotic therapy, and increased surgical experience. PMID- 26815418 TI - Erratum to: Risk assessment and management in hand and facial tissue transplantation. PMID- 26815417 TI - Risk assessment and management in hand and facial tissue transplantation. AB - PURPOSE: Since hand and facial tissue transplantation are new treatments, risk data must be derived from early reports of the few cases done to date combined with extrapolations from other procedures with similar risks. This manuscript summarizes data from both sources including eight separate studies that measure the real and perceived risks associated with hand and facial tissue transplantation. METHODS: Real Risks: Several large clinical studies describing risk data from kidney transplant recipients (10-years experience) and risk data from 49 human hand transplants in 33 recipients (>10 years experience) were reviewed. Perceived Risks: Over 500 subjects with different life experiences (facially disfigured, amputees, laryngectomees, kidney transplant recipients, transplant and reconstructive surgeons, and controls) were surveyed using a standardized and validated risk assessment instrument. RESULTS: Real Risks: Contrary to earlier estimates the risks of acute rejection are higher (80-85%) while the risks of chronic rejection (<5%) and other complications are lower than previously reported. Perceived Risks: Despite different life experiences, those questioned would accept similar amounts of risk to receive different types of transplant procedures (hand, foot, face, larynx, and kidney) but all would accept the most risk for a facial tissue transplant. Kidney transplant recipients, who live with the risks of immunosuppression, would accept the most risk while facially disfigured individuals and reconstructive surgeons, who have real-life experience with facial disfigurement, would accept the least. CONCLUSIONS: These studies contribute to the growing body of risk data necessary for moving hand and face transplantation into mainstream medicine. PMID- 26815419 TI - Thromboprophylaxis following major skeletal trauma: a systematic review. AB - PURPOSE: Venous thromboembolic disease following skeletal polytrauma is a major issue for trauma surgeons, but there is no consensus of opinion regarding the optimal form of prophylaxis. The purpose of this paper was to compare the incidence of venous thromboembolic events (VTE) after major skeletal trauma managed with different prophylactic methods and their combinations. METHODS: A search of AMED, CINAHL, Cochrane Library, EMBASE and MEDLINE databases was performed from their inception to July 2010. A search of unpublished literature databases was undertaken. All randomised controlled trials assessing the incidence of VTE events between two or more forms of thromboprophylaxis for patient following major skeletal trauma were included. Two reviewers independently identified all eligible articles, extracted the data, and critically appraised all included publications using the Critical Appraisal Skills Programme tool. RESULTS: A total of 11 papers were identified. The findings of this study suggest that low molecular weight heparin (LMWH) may be superior to low dose heparin (LDH), and that LMWH should be used in addition to mechanical prophylaxis measures in patients following major skeletal trauma. There is limited evidence for the use of electrostimulation. There appeared to be no significant difference between the use of LDH compared to calf compression devices. However, the evidence-base was insufficient in both size and methodological quality. CONCLUSIONS: There is currently insufficient research to be able to inform trauma surgeons as to the optimal method of thromboprophylaxis for patients following major skeletal trauma. PMID- 26815420 TI - Carcinoid tumor of the appendix: report on ten cases. AB - AIM: To conduct a retrospective analysis of the incidence and long-term outcomes of carcinoid tumor of the appendix in emergency appendectomies. METHODS: From a histopathologic database of 2197 appendectomies from a single center, all appendiceal carcinoid tumors were identified and case notes reviewed. Demographic data, clinical presentation, histopathology, operative reports, and survival were scored and compared with those reported in the literature. RESULTS: Ten patients (0.45%) with appendiceal carcinoid tumor were identified (2 male, 8 female; mean age, 29.2 years; age range, 14-56 years). In all cases, the clinical presentation resembled the symptoms of acute appendicitis. Open appendectomy was performed in all patients. All tumors were located at the tip of the appendix, with a mean diameter of 0.4 cm (range, 0.1-0.9 cm), and the mesoappendix was invaded in one patient. No patient had repeat surgery after the initial operation. After a mean follow-up period of 55 months (range, 26-82 months), all patients were alive and disease- and symptom-free. CONCLUSION: To conclude, carcinoid tumors are extremely rare, and the diagnosis is often made after surgery. We emphasise the value of obtaining histopathological analysis of every removed appendix because visual examination does not always correlate with later pathological examination. Furthermore, small appendiceal carcinoids (<1 cm) have an excellent prognosis after appendectomy. PMID- 26815421 TI - Lung tissue apoptosis in abdominal hypertension : Apoptosis and necrosis of lung tissue in abdominal hypertension. AB - OBJECTIVES: The aim of this study was to evaluate lung tissue histopathologic changes and the number of apoptosis with the increase of abdominal pressure. METHODS: The study rats were randomly assigned into the following five groups: a sham operated group and groups 1, 2, 3 and 4, in which the intra-abdominal pressure was increased to 11, 15, 18 and 22 mmHg for 60 min, respectively. Lungs were harvested for histopathologic changes and the tissue apoptotic analysis were carried out in a blinded manner. RESULTS: All of the data showed that the number of apoptotic cells and necrosis were increased in accordance with the pressure level. However, this increase was statistically significant, especially in groups 3 and 4 (18 and 22 mmHg, respectively; p < 0.05) when compared to the sham operated rats. There were no differences observed between groups 1 and 2 (11 and 15 mmHg, respectively) and the sham operated rats. There was also no difference between groups 1 and 2. There were findings of coagulation necrosis and the number of apoptotic cells linearly increased when the abdominal pressure was increased. The cut-off value was 15 mmHg. CONCLUSION: The available findings suggest that intra-abdominal pressure greater than 15 mmHg could irreversibly damage pulmonary cells and both coagulation necrosis parameters and the number of apoptosis increase in accordance with the pressure level. PMID- 26815422 TI - Correlation between risk factors and subsequent surgical management following internal fixation of intracapsular femoral neck fractures in patients under the age of 60 years. AB - PURPOSE: Regarding intracapsular femoral neck fractures, the main focus of research is the correlation between fracture-related complications and prognostic factors. To evaluate the correlation between complications required surgery (fracture-related treatment) and, among others, several less extensively investigated prognostic factors (day of surgery, co-morbidities, hospital type) in a 2-year period following internal fixation in patients under the age of 60 years with intracapsular femoral neck fracture. METHODS: A retrospective analysis of femoral neck fractures occurring in Hungary in 2000 was undertaken, based on data obtained from the National Health Insurance Fund Administration. The data were validated and completed by a questionnaire carried out in all of the 60 institutions enrolled. The effects of prognostic factors were analyzed by uni- and multivariate logistic regression in three groups: all fracture-related treatments and non-prosthetic (NPT) and prosthetic treatments (PT). RESULTS: Out of 413 patients, 17.9% required further fracture-related treatment. In 7.7% of patients, NPT and in 10.2% of patients, PT was performed. Fracture displacement (odds ratio [OR] = 2.24), weekend surgery (OR = 2.35), infections (OR = 3.68), central nervous system-related co-morbidities (OR = 3.64), and the county hospital level of management (OR = 2.36) were associated with significantly increased risk for further surgery. CONCLUSIONS: To reduce the influence of risk factors, standardization of the substantive traumatologic and orthopedic professional guidelines, as well as the introduction of the "common orthopedic trauma patient care" (British model) are suggested. To achieve high-quality standardized patient management, personal and material conditions are required to be accessible every day of the week. In the presence of co-morbidities, reduction of their harmful effects should be a major consideration by focusing on the patient in the peri-operative periods. PMID- 26815424 TI - Results of locked flexible intramedullary nailing of metacarpal fractures: a case series. AB - PURPOSE: We present our case series on the use of flexible locked intramedullary nails in the management of metacarpal fractures. METHODS: This was a prospective study over a period of 2 years of all patients with metacarpal fractures with 100% displacement or rotational deformity operated by the flexible locked intramedullary nails from January 2008 to April 2010 at Queen Elizabeth Hospital, Gateshead, UK RESULTS: Twenty-six patients with fractures of metacarpal neck and shaft were included in the study. All fractures went on to union by an average of 6.3 weeks with full metacarpophalangeal joint movement and grip strength. CONCLUSION: In our experience, this device helps to achieve good functional results with minimal soft tissue disruption and complications in the management of unstable metacarpal fractures. PMID- 26815423 TI - Influence of timing and oral anticoagulant/antiplatelet therapy on outcomes of patients affected by hip fractures. AB - BACKGROUND: Patients undergoing surgical procedures are usually asked to discontinue any anticoagulant/antiplatelet therapy and delay surgery for at least 5 days to reduce the risk of major bleeding and spinal hematoma. AIM: The purpose of this study was to determine if this strategy is suitable for patients on anticoagulant/antiplatelet therapy affected by a hip fracture, evaluating the effect of anticoagulant/antiplatelet therapy and surgical timing on mortality and complication rates for patients affected by a hip fracture. PATIENTS AND METHODS: We performed an observational study on patients referring to our hospital for a hip fracture. We evaluated patients on warfarin, ticlopidine, and aspirin therapy matched to patients not on anticoagulant or antiplatelet therapy, out of 875 consecutive patients treated for a hip fracture in a 5-year period. Blood loss, blood transfusions, length of hospitalization, walking ability, complications, and mortality at 1 year of follow-up were recorded. Kruskal-Wallis, Mann-Whitney U, and logistic regression statistical tests were performed. RESULTS: Patients on warfarin therapy operated more than 5 days after admission showed significantly higher complication and mortality rates compared to all other patients. Two critical factors were identified: warfarin therapy and excessive time to surgery; these factors are not significant if taken alone, while they become a high-risk factor if taken together. CONCLUSION: The "discontinue drug, and delay surgery" strategy is not suitable for patients on anticoagulant (warfarin) therapy affected by a hip fracture. PMID- 26815425 TI - Multidetector computed tomography of acute vascular injury in blunt abdominal/pelvic trauma: imaging predictors of treatment. AB - PURPOSE: The purpose of this study was to analyze the multidetector computed tomography (MDCT) morphologic characteristics of non-aortic acute vascular injuries (AVI) in patients with blunt abdominopelvic trauma that predict treatment. METHODS: CT scans of 65 trauma patients with non-aortic AVI were reviewed. AVI morphology was categorized as linear or round. The organ of involvement, location of hemorrhage, initial size of hematoma, and hemodynamic status were recorded. Expansion rates of the hematoma were calculated in 40 patients who had delayed imaging. Multivariate regression was used to analyze the morphologic features of AVI and treatment. RESULTS: Patients with linear AVI were four times more likely to require aggressive treatment (surgery or embolization) than those with a round morphology, independent of the hemodynamic status. There was no main effect of the organ involved, location of hemorrhage, initial bleed size, or expansion rate on the probability of aggressive treatment. CONCLUSION: The location, initial size, and expansion rate of AVI are not significant predictors of aggressive treatment with surgery or embolization. Linear morphology of AVI, however, is more likely to require aggressive treatment than round AVI, independent of the hemodynamic status. Linear AVI likely reflects a spurting jet of active extravasation, whereas round AVI likely represents a pseudoaneurysm or slow bleed. PMID- 26815427 TI - Response to the comment of Brusselaers et al. questioning the clinical benefit of circulating free DNA/neutrophil extracellular traps (cfDNA/NETs) as a laboratory marker for outcome prediction after severe burn injuries. PMID- 26815426 TI - Outcome prediction in severe burn injury: clinical versus laboratory markers. PMID- 26815429 TI - Implications of dynamic imine chemistry for the sustainable synthesis of nitrogen heterocycles via transimination followed by intramolecular cyclisation. AB - An exploration of a tandem approach to the sustainable synthesis of N heterocycles from readily available N-aryl benzylamines or imines and ortho substituted anilines is described, which demonstrates, for the first time, an important synthetic application of dynamic imine chemistry. The key features to the successful development of this protocol include the utilisation of N-aryl benzylamines as imine precursors in transimination, the occurrence of transimination in acetonitrile in the absence of any catalysts, an intramolecular nucleophilic addition occurring in the newly formed imine causing irreversible transimination, and the tandem event occurring under green conditions. PMID- 26815428 TI - Maternal Fatty Acids and Their Association with Birth Outcome: A Prospective Study. AB - Maternal nutrition, especially LCPUFA, is an important factor in determining fetal growth and development. Our earlier cross sectional study reports lower docosahexanoic acid (DHA) levels at the time of delivery in mothers delivering low birth weight (LBW) babies. This study was undertaken to examine the role of the maternal omega-3 and omega-6 fatty acid profile across the gestation in fetal growth. This is a hospital based study where women were recruited in early gestation. Maternal blood was collected at 3 time points, i.e., T1 = 16th-20th week, T2 = 26th-30th week and T3 = at delivery. Cord blood was collected at delivery. At delivery, these women were divided into 2 groups: those delivering at term a baby weighing >2.5kg [Normal birth weight (NBW) group] and those delivering at term a baby weighing <2.5kg [LBW group]. The study reports data on 111 women recruited at T1, out of which 60 women delivered an NBW baby at term and 51 women delivered an LBW baby at term. Fatty acids were analysed using gas chromatography. At T1 of gestation, maternal erythrocyte DHA levels were positively (p<0.05) associated with baby weight. Maternal plasma and erythrocyte arachidonic acid and total erythrocyte omega-6 fatty acid levels at T2 were higher (p<0.05 for both) in the LBW group. Total erythrocyte omega-3 fatty acid levels were lower (p<0.05) while total erythrocyte omega-6 fatty acid levels were higher (p<0.05) in the LBW group at delivery. Our data demonstrates the possible role of LCPUFA in the etiology of LBW babies right from early pregnancy. PMID- 26815430 TI - Substance P promotes diabetic wound healing by modulating inflammation and restoring cellular activity of mesenchymal stem cells. AB - Diabetic ulceration is one of the most debilitating complications of diabetes and is the main cause of amputation. The diabetic environment is characterized by prolonged inflammation and abnormal angiogenesis, leading to delayed wound healing. Thus, regulation of inflammation and neovascularization is considered a desirable target for diabetes. The critical purpose of this study was to determine whether systemically administered Substance P (SP) could promote wound healing in diabetic environments via suppression of inflammation, induction of angiogenesis, and mobilization of stem cells. The effect of SP was assessed by analyzing epidermal and dermal recovery, vessel formation, cytokine secretion profile, and the stem cell pool in the circulation and bone marrow. Compared with the vehicle-treated group, the SP-treated group exhibited more rapid wound coverage, reduced infiltration of leukocytes, suppression of injury-mediated enlargement of the spleen and mesenteric lymph nodes, reduced tumor necrosis factor-alpha levels, increased interleukin-10, elevated pool of M2 monocytes and vascular endothelial growth factor levels in the blood. Moreover, the stem cell pool in the bone marrow, which is very low in diabetes, was markedly restored by SP to normal levels, which could provide a favorable environment to facilitate wound healing in diabetes. This result demonstrates, for the first time, a possible application of SP for the treatment of diabetic complications, including diabetic ulcers. PMID- 26815431 TI - Superconductivity in Bismuth. A New Look at an Old Problem. AB - To investigate the relationship between atomic topology, vibrational and electronic properties and superconductivity of bismuth, a 216-atom amorphous structure (a-Bi216) was computer-generated using our undermelt-quench approach. Its pair distribution function compares well with experiment. The calculated electronic and vibrational densities of states (eDOS and vDOS, respectively) show that the amorphous eDOS is about 4 times the crystalline at the Fermi energy, whereas for the vDOS the energy range of the amorphous is roughly the same as the crystalline but the shapes are quite different. A simple BCS estimate of the possible crystalline superconducting transition temperature gives an upper limit of 1.3 mK. The e-ph coupling is more preponderant in a-Bi than in crystalline bismuth (x-Bi) as indicated by the lambda obtained via McMillan's formula, lambdac = 0.24 and experiment lambdaa = 2.46. Therefore with respect to x-Bi, superconductivity in a-Bi is enhanced by the higher values of lambda and of eDOS at the Fermi energy. PMID- 26815432 TI - Reversal of MicroRNA Dysregulation in an Animal Model of Pulmonary Hypertension. AB - BACKGROUND: Animals models have played an important role in enhancing our understanding of the pathogenesis of pulmonary arterial hypertension (PAH). Dysregulation of the profile of microRNAs (miRNAs) has been demonstrated in human tissues from PAH patients and in animal models. In this study, we measured miRNA levels in the monocrotaline (MCT) rat model of PAH and examined whether blocking a specific dysregulated miRNA not previously reported in this model, attenuated PAH. We also evaluated changes in miRNA expression in lung specimens from MCT PAH rats overexpressing human prostacyclin synthase, which has been shown to attenuate MCT PAH. METHODS: Expression levels of a panel of miRNAs were measured in MCT-PAH rats as compared to naive (saline) control rats. Subsequently, MCT PAH rats were injected with a specific inhibitor (antagomiR) for miR-223 (A223) or a nonspecific control oligonucleotide (A-control) 4 days after MCT administration, then weekly. Three weeks later, RV systolic pressure and RV mass were measured. Total RNA, isolated from the lungs, microdissected pulmonary arteries, and right ventricle, was reverse transcribed and real-time quantitative PCR was performed. MiRNA levels were also measured in RNA isolated from paraffin sections of MCT-PAH rats overexpressing prostacyclin synthase. RESULTS: MiRs 17, 21, and 223 were consistently upregulated, whereas miRs 126, 145, 150, 204, 424, and 503 were downregulated in MCT PAH as compared to vehicle control. A223 significantly reduced levels of miR-223 in PA and lungs of MCT PAH rats as compared to levels measured in A-control or control MCT PAH rats, but A223 did not attenuate MCT PAH. Right ventricular mass and right ventricular systolic pressure in rats treated with A223 were not different from values in A-control or MCT PAH rats. In contrast, analysis of total RNA from lung specimens of MCT PAH rats overexpressing human prostacyclin synthase (hPGIS) demonstrated reversal of MCT induced upregulation of miRs 17, 21, and 223 and an increase in levels of miR-424 and miR-503. Reduction in bone morphogenetic receptor 2 (BMPR2) messenger (m)RNA expression was not altered by A223, whereas human prostacyclin synthase overexpression restored BMPR2 mRNA to levels in MCT PAH to levels measured in naive controls. CONCLUSIONS: Inhibition of miR-223 did not attenuate MCT PAH, whereas human prostacyclin synthase overexpression restored miRNA levels in MCT PAH to levels detected in naive rats. These data may establish a paradigm linking attenuation of PAH to restoration of BMPR2 signaling. PMID- 26815433 TI - Epidemiological and clinical features for cefepime heteroresistant Escherichia coli infections in Southwest China. AB - Phenotypic heteroresistance (PHR) is common in a weight of microbes and plays an important role in the evolution of antibiotic resistance. However, PHR to cefepime (FEP-PHR) among invasive Escherichia coli (E. coli) has not been reported. This study aimed to report the characteristics of invasive E. coli with FEP-PHR traits and further to investigate the predisposing factors for its acquisition. A retrospective case-control study was conducted in a teaching hospital in Southwest China. A total of 319 successive and non-duplicate E. coli strains were isolated from blood and other sterile body fluids between July 2011 and August 2013. Among the seventy (70/319, 21.9 %) isolates harboring FEP-PHR traits, 30 (42.9 %) isolates were isolated from blood, 14 (20.0 %) isolates were isolated from bile, and 13 (18.6 %) isolates were isolated from drainage. FEP-PHR isolates were verified by population analysis profile (PAP) assays. Male gender, receipt of total parenteral nutrition, cephalosporins exposure, and production of extended spectrum betalactamases (ESBL) were independent risk factors for the acquisition of invasive E. coli with FEP-PHR traits. Pulsedfield gel electrophoresis (PFGE) revealed clonal diversity among the FEP-PHR isolates. The prevalence of heteroresistance to cefepime among invasive E. coli isolates merits great attention and heteroresistance may lead to the emergence of resistance strains. Therefore, systematical analysis of risk factors, careful interpretation of antibiotic susceptibility results and appropriate prescription of therapeutic strategy could help to prevent misreporting and therapeutic failure. PMID- 26815434 TI - In vivo development of daptomycin resistance in vancomycin-susceptible methicillin-resistant Staphylococcus aureus severe infections previously treated with glycopeptides. AB - Our aim was to describe the clinical and microbiological features of four cases of severe vancomycin-susceptible methicillin-resistant Staphylococcus aureus (MRSA) infections in which the vancomycin non-susceptibility development and daptomycin resistance occurred under therapy with teicoplanin (three cases) and daptomycin switched to vancomycin (one case). Clinical data were retrospectively reviewed. On nine clinical epidemiologically unrelated daptomycin-susceptible (DAP-S) and daptomycin-resistant (DAP-R) MRSA, we performed: (i) DAP-VAN-TEC-CFX RIF minimum inhibitory concentrations (MICs); (ii) glycopeptide resistance detection (GRD) by delta-hemolysis; (iii) glycopeptide population analysis; (iv) molecular characterization by PFGE-MLST-SCCmec-agr-typing; (v) rpoB and mprF single nucleotide polymorphisms (SNPs); (vi) dltA-mprF-atl-sceD expression by real-time quantitative polymerase chain reaction (qPCR). Three out of the four patients did not survive despite salvage treatment; two died with active MRSA infection and one died because of Stenotrophomonas maltophilia sepsis. The fourth patient, in which a reversion to a DAP-S phenotype occurred, survived with daptomycin plus trimethoprim/sulfamethoxazole and oxacillin treatment, and endovascular device removal. Daptomycin resistance development was preceded by a stable heterogeneous vancomycin-intermediate S. aureus (hVISA) or VISA phenotype acquisition, while in one case, daptomycin resistance was preceded by an unstable daptomycin heteroresistance (hDAP) behavior reverting to DAP-S during vancomycin plus rifampin therapy followed by high doses of daptomycin. All DAP-R strains showed hVISA or DAP-R traits, including mutations and/or up-regulation of genes involved in cell wall turnover and cell membrane perturbation. In our study, daptomycin resistance arose during glycopeptide therapy. The emergence of DAP-R isolates was preceded by a stable VISA or hVISA phenotype or by instability reverting to a DAP-S heteroresistant phenotype. Daptomycin, as first-line therapy for the treatment of severe MRSA infections, should be used at optimal dosage combined with other agents such as beta-lactams, to prevent daptomycin resistance occurrence. PMID- 26815436 TI - Sensory Drive Mediated by Climatic Gradients Partially Explains Divergence in Acoustic Signals in Two Horseshoe Bat Species, Rhinolophus swinnyi and Rhinolophus simulator. AB - Geographic variation can be an indicator of still poorly understood evolutionary processes such as adaptation and drift. Sensory systems used in communication play a key role in mate choice and species recognition. Habitat-mediated (i.e. adaptive) differences in communication signals may therefore lead to diversification. We investigated geographic variation in echolocation calls of African horseshoe bats, Rhinolophus simulator and R. swinnyi in the context of two adaptive hypotheses: 1) James' Rule and 2) the Sensory Drive Hypothesis. According to James' Rule body-size should vary in response to relative humidity and temperature so that divergence in call frequency may therefore be the result of climate-mediated variation in body size because of the correlation between body size and call frequency. The Sensory Drive Hypothesis proposes that call frequency is a response to climate-induced differences in atmospheric attenuation and predicts that increases in atmospheric attenuation selects for calls of lower frequency. We measured the morphology and resting call frequency (RF) of 111 R. simulator and 126 R. swinnyi individuals across their distributional range to test the above hypotheses. Contrary to the prediction of James' Rule, divergence in body size could not explain the variation in RF. Instead, acoustic divergence in RF was best predicted by latitude, geography and climate-induced differences in atmospheric attenuation, as predicted by the Sensory Drive Hypothesis. Although variation in RF was strongly influenced by temperature and humidity, other climatic variables (associated with latitude and altitude) as well as drift (as suggested by a positive correlation between call variation and geographic distance, especially in R. simulator) may also play an important role. PMID- 26815437 TI - The European trauma course: trauma teaching goes European. PMID- 26815438 TI - Focus on spinal fractures in the elderly. PMID- 26815435 TI - Anti-osteoporotic effects of Pueraria candollei var. mirifica on bone mineral density and histomorphometry in estrogen-deficient rats. AB - Although it has been clearly shown that Pueraria mirifica and its phytoestrogens can mimic estrogen in preventing bone loss, as osteoporosis is an asymptomatic disease, the therapeutic effects of P. mirifica should be acknowledged. In this study, 6-month-old female rats were ovariectomized, kept for 4 weeks to induce bone loss, divided into five groups, and treated with P. mirifica at doses of 0, 5, 25, and 50 mg/kg BW/day (PM0, PM5, PM25, and PM50 groups, respectively) or 7 mg/kg BW/day of puerarin (PU group) for 12 weeks. Only the trabecular bone mineral densities (BMDs) of tibia metaphysis (at the 12th, 14th, and 16th week) and total and trabecular BMDs of L4 (at the 16th week) of the PM50 group were significantly higher than those of the PM0 group. However, the BMDs of tibia metaphysis and L4 at the 16th week of the study period were kept significantly lower than those of the 0 week, and the BMD was also significantly lower than that of the 4th week for tibia metaphysis. The trabecular bone area (BV/TV), trabecular number (Tb.N), and osteoblast surface (Ob.S/BS) were significantly higher, and trabecular space (Tb.Sp) was significantly lower in the PM50 group, as compared with those of the PM0 group. This study indicates that P. mirifica could be used as an anti-osteoporotic agent for postmenopausal women. Since P. mirifica could mainly retain bone mass at the levels before bone loss is initiated, the use of other anabolic agents in combination with P. mirifica is recommended for osteoporotic patients. PMID- 26815439 TI - Percutaneous cement augmentation techniques for osteoporotic spinal fractures. AB - Minimally invasive vertebral augmentation-based techniques have been used for the treatment of spinal fractures (osteoporotic and malignant) for approximately 25 years. In this review, we try to give an overview of the current spectrum of percutaneous augmentation techniques, safety aspects and indications. Crucial factors for success are careful patient selection, proper technique and choice of the ideal cement augmentation option. Most compression fractures present a favourable natural course, with reduction of pain and regainment of mobility after a few days to several weeks, whereas other patients experience a progressive collapse and persisting pain. In this situation, percutaneous cement augmentation is an effective treatment option with regards to pain and disability reduction, improvement of quality of life and ambulatory and pulmonary function. PMID- 26815440 TI - Reduced loosening rate and loss of correction following posterior stabilization with or without PMMA augmentation of pedicle screws in vertebral fractures in the elderly. AB - BACKGROUND: Therapy of vertebral fractures in the elderly is a growing challenge for surgeons. Within the last two decades, the use of polymethylmethacrylate (PMMA) in the treatment of osteoporotic vertebral fractures has been widely established. Besides vertebroplasty and kyphoplasty, the augmentation of pedicle screws with PMMA found widespread use to strengthen the implant-bone interface. Several studies showed an enhanced pullout strength of augmented screws compared to standard pedicle screws in osteoporotic bone models. To validate the clinical relevance, we analyzed postoperative radiologic follow-up data in regard to secondary loss of correction and loosening of pedicle screws in elderly patients. MATERIALS AND METHODS: In this retrospective comparative study, 24 patients admitted to our level I trauma center were analyzed concerning screw loosening and secondary loss of correction following vertebral fracture and posterior instrumentation. Loss of correction was determined by the bisegmental Cobb angle and kyphosis angle of the fractured vertebra. Follow-up computed tomography (CT) scans were used to analyze the prevalence of clear zones around the pedicle screws as a sign of loosening. RESULTS: In 15 patients (mean age 76 +/- 9.3 years) with 117 PMMA-augmented pedicle screws, 4.3 % of screws showed signs of loosening, whereas in nine patients (mean age 75 +/- 8.2 years) with 86 uncemented screws, the loosening rate was 62.8 %. Thus, PMMA-augmented pedicle screws showed a significantly lower loosening rate compared to regular pedicle screws. Loss of correction was minimal, despite poor bone quality. There was significantly less loss of correction in patients with augmented pedicle screws (1.1 degrees +/- 0.8 degrees ) as compared to patients without augmentation (5 degrees +/- 3.8 degrees ). CONCLUSION: The reinforcement of pedicle screws using PMMA augmentation may be a viable option in the surgical treatment of spinal fractures in the elderly. PMID- 26815441 TI - Intraoperative PEEP-ventilation during PMMA-injection for augmented pedicle screws: improvement of leakage rate in spinal surgery. AB - BACKGROUND: Within the last two decades the use of polymethylmethacrylate (PMMA) in the treatment of osteoporotic vertebral fractures has been established widely. Several techniques of cement application in spinal surgery have been described. Besides classical vertebroplasty, kyphoplasty and related techniques that reinforce stability of the fractured vertebral body itself, augmentation of pedicle screws became an issue in the past 10 years. Aim of this technique is strengthening of the implant-bone-interface and the prevention of loosening and failure of posterior instrumentation in limited bone quality due to osteoporosis. PMMA use in spinal surgery always bears the risk of cement leakage and cement embolism. There are only few publications dealing with cement leakage in pedicle screw augmentation. We examined our cohort concerning incidence and type of leakage in comparison to the literature. In particular, we evaluated a possible role of intrathoracic pressure during cementation procedure. PATIENTS AND METHODS: In this retrospective study 42 patients were included. Mean age was 74 (57-89) years. 311 fenestrated, augmented screws were analyzed postoperatively concerning leakage and subsequent pulmonary embolism of cement particles. Overall, there was a leakage rate of 38.3 %, and 28.6 % of patients showed pulmonary embolism of PMMA. During surgery, patients were in part ventilated with a positive end-expiratory pressure (PEEP) of 15 cmH2O during cement injection. These individuals showed significantly less leakage locally as well as less PMMA emboli in the pulmonary circulation in contrast to patients ventilated without increased PEEP. CONCLUSION: PEEP elevation during administration of PMMA via fenestrated pedicle screws is reducing the leakage rate in spinal surgery. These beneficial effects warrant further evaluation in prospective studies. PMID- 26815442 TI - Cervical spine fractures in the elderly: morbidity and mortality after operative treatment. AB - PURPOSE: Although there are currently many different strategies and recommendations in the therapy of cervical spine fractures in elderly patients, there are still no generally accepted treatment algorithms. The aim of the present study was to analyze the morbidity, mortality, and outcome of operated cervical spine injuries in the elderly. METHODS: This study presents a retrospective review of 69 patients aged 65 years or older admitted to our level I trauma center with cervical spine injury, who had undergone surgical treatment. The data were acquired by analysis of the hospital inpatient enquiry system and radiological review. RESULTS: The ratio between male and female patients was 37:32. The average age of the patients was 76 years (ranging from 65 to 96 years) for males and 80 years (ranging from 66 to 93 years) for females. Injury to the cervical spine was caused by low-energy trauma in 71 % and high-energy trauma in 29 %, respectively. 55.1 % sustained isolated cervical spine injuries, 39.1 % injuries to two adjacent vertebrae, 2.9 % injuries to three adjacent vertebrae, and 2.9 % an odontoid fracture combined with associated fracture(s) in non contiguous vertebra(e). Isolated spine injury level was dominated by C2 (47.8 %). The most common site for injuries to two adjacent vertebrae was observed at C6/C7 (14.5 %). The morbidity included cerebral complications, respiratory complications, Clostridium difficile-associated disease, heart failure, and acute renal failure. Operative complications included dislocation/malposition, neurovascular lesions, wound infection, and transient swallowing difficulty. The mortality rate at 3 months was 26.1 %, with an in-hospital mortality of 21.7 %. Age was associated with mortality at 3 months. A cervical fracture-induced neurological deficit was documented in 26.1 %, resulting in a mortality of 44.4 % (8/18). Twenty-seven of 33 patients living at home/nursing home at the time of injury returned to their home/nursing home after their hospitalization. The overall outcome was predominantly related to age and the severity of neurological deficit. CONCLUSIONS: In elderly patients with cervical spine fractures, the hospital course is complicated by medical issues and early mortality rates are significant. Therefore, treatment strategies should be carefully individualized to the patients and their comorbidities. PMID- 26815443 TI - Do cervical spine X-rays for trauma have clinically significant incidental findings? AB - OBJECTIVES: About 800,000 cervical X-rays for trauma are taken every year in the USA. Those X-rays are reviewed by orthopedic specialists in the emergency room (ER) for traumatic findings. The quantity of incidental atraumatic findings in this very prevalent examination is unknown. We sought to determine the incidence of those findings. METHODS: We retrospectively reviewed 521 consecutive cervical X-rays of patients with a whiplash injury that visited our ER from February to July 2010. X-rays that were technically insufficient were excluded. This left 356 X-rays that met the inclusion criteria, which were analyzed for incidental findings. The examinations were reviewed by five staff radiologists for incidental findings. The findings were reviewed and classified. RESULTS: We identified incidental X-ray findings in 22 of the 356 patients (6.2 %) who underwent X-ray of the cervical spine during their visit to the ER. Stenosis with disk narrowing was the most common finding (2.8 %), followed by congenital anomaly of the cervical spine (2.2 %). Other findings were enlarged sella turcica (0.6 %), carotid atherosclerosis (0.3 %), and calcification of the stylomastoid ligament (0.3 %). Older age was found to be a risk factor for an incidental finding (p < 0.0001). CONCLUSION: Incidental findings in the cervical spine were associated with older age. Awareness of the prevalence of incidental findings is important in order to ensure that they are detected and managed appropriately. PMID- 26815444 TI - Motorcycle injuries at a tertiary referral hospital in Kenya: injury patterns and outcome. AB - BACKGROUND: The rise in the use of motorcycles in Kenya in the last 10 years has been associated with increased injury rates. Between 2004 and 2009, motorcycle injuries increased at a rate of 29 % and, in some hospitals, motorcycle users have become the predominant road user category injured. Although most road traffic injuries occur in Nairobi, there has been no previous account of motorcycle injury and associated outcomes at its main hospital. OBJECTIVE: To describe the injury patterns and outcomes following motorcycle trauma at the Kenyatta National Hospital. METHODS: All motorcycle trauma admissions during one calendar year were analyzed. The data captured included demographics, injury patterns and outcomes, lengths of hospital stay, hospitalization cost, and early hospital mortality. Factors associated with outcomes were analyzed by univariate and multivariate means. The probability of survival was estimated using the Trauma and Injury Severity Score (TRISS) methodology for each patient. RESULTS: Two hundred and five patients were reviewed. Motorcycle trauma admissions formed 22.3 % of all road traffic injury admissions. Male riders predominated. The average age and modal age group was 30.78 and 21-30 years, respectively. Half of riders and 20 % of passengers used protective helmets. Injuries were mostly to the extremities (60.7 %) and head/neck (32.07 %), and the average Injury Severity Score (ISS) was 7.57 + 4.0 (median 9.0). At 2 weeks, 9.0 % of patients had died. The estimated probability of survival ranged from 0.86 to 0.97. Surgical interventions were needed for 51.7 % of patients. The mean length of stay in the hospital was 24.3 days, while the cost of treatment was 31,783 Kenya Shillings (Kshs). Injury severity (P < 0.001), admission to the intensive care unit (ICU) (P < 0.001), non-surgical treatment (P = 0.003), blood transfusion (P = 0.029), head injury (P < 0.001), and low Glasgow Coma Scale (GCS) score at admission were significantly associated with mortality. CONCLUSION: Injuries to the lower limbs and the head predominate in motorcycle trauma. The high mortality rate, need for surgery in the majority of patients, and prolonged admission days call for motorcycle control and expedited care. Significant head injury mortality calls for efforts to embrace helmet laws for riders and passengers. PMID- 26815445 TI - Lactic acidosis is associated with multiple organ failure and need for ventilator support in patients with severe hemorrhage from trauma. AB - PURPOSE: Lactate is a biomarker for hypoperfusion and subsequent resuscitation in trauma. It is also a predictor of mortality, but few studies have correlated lactate levels with relevant morbidities after trauma. METHODS: A retrospective review was performed of severely injured trauma patients entered into the Trauma Registry of the German Society for Trauma Surgery (TR-DGU) between 2002 and 2008. Adults requiring intensive care were categorized into two groups: lactate and no lactate. The lactate group had three subgroups: normal, elevated, and high lactate. Mean multiple organ failure (MOF) rates and composite endpoint of time (days) to complete organ failure resolution (CTCOFR) for 14 and 21 days and ventilator-free days (VFD) were compared, as well as other endpoints. RESULTS: We analyzed 2,949 patients, of which 1,199 had lactate measurements. The percentage of patients with MOF increased in each higher lactate subgroup (p < 0.001), as did the mean CTCOFR14 and CTCOFR21 scores (p < 0.001 and < 0.001, respectively). Conversely, the mean VFD decreased in each higher lactate subgroup (p < 0.001). Thus, patients in the elevated and high lactate subgroups had greater MOF rates; required more days, on average, to resolve organ failure; and required more days of ventilator support than patients in the normal lactate subgroup. CONCLUSION: Elevated blood lactate levels from trauma were closely correlated with worse outcomes. Thus, lactate shows promise as a biomarker for resuscitation as well as a predictor of mortality. Furthermore, this study supports its use in critical care trials as an outcome measure. PMID- 26815446 TI - Symptomatic venous thromboembolism in Asian major trauma patients: incidence, presentation and risk factors. AB - BACKGROUND: Trauma patients are known to be at increased risk of venous thromboembolism (VTE), and pulmonary embolism (PE) is one of the preventable causes of mortality in trauma patients. The incidence of VTE in Asian populations was believed to be lower than in Caucasians, but the recent literature suggests that this is not the case. The purpose of this study was to assess the incidence of VTE in Asian major trauma patients and to examine the manner of presentation, use of prophylaxis and risk factors for VTE. While other studies of VTE have addressed general and high-risk populations within Asia, our study is one of the few to examine Asian major trauma patients. METHODS: Data for all patients with VTE were extracted from the Singapore General Hospital trauma database over a 10 year period from 1998 to 2007. Patient profiles and clinical factors were compared to patients without a diagnosis of VTE admitted with injuries in the same time period. RESULTS: There were 8,615 patients entered into our database in this 10-year period. Thirty-four patients had VTE, with an overall incidence of 0.39 %. Thirteen patients had pulmonary embolism, an incidence of 0.15 %. Of note, 30 % of patients with deep vein thrombosis (DVT) presented with fever alone without limb symptoms. Almost all 34 patients who developed VTE had either head injury, a spinal cord injury or a pelvic/extremity injury. Eighteen patients had head injury, 22 patients sustained pelvic or extremity injury, and three patients had spinal cord injury with paraplegia. Head injury and spinal cord injury with neurologic sequelae were statistically significant risk factors for VTE (p < 0.05). CONCLUSION: The incidence of symptomatic VTE in the Asian trauma population is no lower than in the West. The incidence found in this study is similar to the incidence of VTE according to a study using data from the American national trauma data bank using similar study methods and with a similar study population. It is also higher than the incidence in the literature for general post-surgical Asian patients. Fever was the presenting factor in some patients and screening for VTE should not be forgotten when assessing fever in the trauma patient. The strong association between head injury, spinal cord injury and VTE confirms that we should pay special attention to VTE prophylaxis for our patients with these injuries. PMID- 26815447 TI - Recovery after stabilising surgery for 'flail chest'. AB - BACKGROUND/PURPOSE: There is a lack of knowledge on respiratory and physical function, mobility and pain following stabilising surgery for 'flail chest'. The purpose of this study was, therefore, to evaluate pain, respiratory function, range of motion and physical function/activity 3 and 6 months after stabilising surgery in patients with 'flail chest' due to trauma. METHOD: Twenty-four patients diagnosed with 'flail chest' were, 3 and 6 months after the trauma, measured with regard to remaining pain, lung volume, breathing movements, and range of motion in the rib cage and thoracic spine. Physical function and level of physical activity were also estimated. RESULTS: Approximately 50 % of the patients had remaining pain after 3 months and 35 % had remaining pain after 6 months. Vital capacity was significantly decreased after 3 and 6 months compared to predicted values: >83 % after 3 months and >86 % after 6 months. There were no significant differences between the injured versus non-injured side in breathing movements, nor between the values of the range of motion between the two test occasions. The results of physical function showed mild to moderate disability 3 months after surgery and some or mild disability at 6 months. The patients were active, performing moderate exercise 1-2 h/week or light physical activities more than 4 h/week at 3 and 6 months. CONCLUSIONS: Patients who had undergone stabilising surgery due to 'flail chest' showed decreased range of motion 3 and 6 months after surgery. Despite decreased range of motion and remaining pain, the breathing movements are synchronic. PMID- 26815448 TI - Percutaneous dilatational tracheostomies in a newly established trauma center: a report from Qatar. AB - BACKGROUND: Percutaneous dilatational tracheostomy (PDT) is a routine surgical procedure for critically ill patients who require prolonged ventilatory support. METHODS: We conducted a retrospective cohort study of all PDTs performed at the adult Trauma Intensive Care Unit (TICU) of Hamad Medical Corporation in Doha, Qatar, from January 2009 through September 2012. For all adult patients, we analyzed the demographic characteristics, mean ventilator time before the procedure, injury severity score (ISS), complications, and outcomes. RESULTS: Of the 1,442 trauma patients admitted to the adult TICU during our study period, 124 (8.5 %) underwent PDT using the Ciaglia Blue Rhino technique. The vast majority were male (94.3 %). The mean age was 35 +/- 15.6 years; mean ventilator time before the procedure, 12 +/- 3 days; and mean ISS, 24.2 +/- 9.3. More than half of patients had head injury (56 %), followed by chest and abdomen (26 %) and cervical spine injuries (18 %). Early complications included difficult tube placement (0.8 %), hypoxemia (0.8 %), minor bleeding (1.6 %), and hypotension (0.8 %), but the vast majority (93 %) of patients had no complications. The procedure-related mortality rate was 0 %. CONCLUSION: PDT is safe and can be performed with minimal complications even in a newly established trauma center. PMID- 26815449 TI - Management of biliary complications following damage control surgery for liver trauma. AB - BACKGROUND: The liver is the most frequently injured solid intra-abdominal organ. The major cause of early death following severe liver trauma is exsanguination. Although perihepatic packing improves survival in severe liver trauma, this leaves parenchymal damage untreated, often resulting in post-traumatic biliary leakage and a subsequent rise in morbidity. The aim of this study was to analyze the incidence and treatment of biliary leakage following the operative management of liver trauma. METHODS: Patients presenting between 2000 and 2009 to Erasmus University Medical Centre with traumatic liver injury were identified. Data from 125 patients were collected and analyzed. Sixty-eight (54 %) patients required operation. All consecutive patients with post-operative biliary complications were analyzed. Post-operative biliary complications were defined as biloma, biliary fistula, and bilhemia. RESULTS: Ten (15 %) patients were diagnosed with post-operative biliary leakage following liver injury. Three patients with a biloma were treated with percutaneous drainage, without further intervention. Seven patients with significant biliary leakage were managed by endoscopic stenting of the common bile duct to decompress the internal biliary pressure. One patient had a relaparotomy and right hemihepatectomy to control biliary leakage and injury of the right hepatic duct. CONCLUSION: Biliary complications continue to occur frequently following damage control surgery for liver trauma. The majority of biliary complications can be managed without an operation. Endoscopic retrograde cholangiopancreatography (ERCP) and internal stenting represent a safe strategy to manage post-operative biliary leakage and bilhemia in patients following liver trauma. Minor biliary leakage should be managed by percutaneous drainage alone. PMID- 26815450 TI - Does ATLS trauma training fit into Western countries: evaluation of the first 8 years of ATLS in Germany. AB - BACKGROUND: With over 2 million certified physicians worldwide, the Advanced Trauma Life Support (ATLS) program is one of the most successful international medical education programs. Germany joined the ATLS program in 2003. Before implementation of the program, there was a controversial discussion as to whether a country like Germany with a long history of trauma care needed ATLS at all. 197 courses with nearly 3,000 providers were performed until December 2010. AIM: We assessed the course evaluations since the implementation of ATLS in Germany using the participants' systematic feedback. METHOD: During the course, each participant evaluated each presentation, skill station, and simulation on a rating scale from 1 to 4 (1 being the best, 4 being the worst). The participants completed the evaluation forms during the course and before they received their results. The course coordinator made sure that all forms were returned. The feedback forms were collected anonymously and were entered into a database. Statistical analysis was performed using frequencies and mean values. RESULTS: The cumulative evaluation of all courses revealed an average performance score of 1.39 (1.06-1.86; n = 197). The lectures, skill stations, and simulations were individually evaluated as follows: lectures 1.61 (1.00-2.81; n = 197), skill stations 1.40 (1.00-2.40; n = 197), and surgical skill stations 1.35 (1.00-2.38; n = 197). Practical skills simulation (case scenarios) received the highest grade of 1.24 (1.00-1.57; n = 197). There were no significant changes during the time concerning the results of the evaluation. CONCLUSION: The overall assessment showed constantly good and excellent evaluations by the participants over the years. In general, skill stations and simulations performed better than lectures. According to these results, the course format is well accepted by the participants and, therefore, can be recommended to all physicians treating trauma patients. Our results also underline the value of such a course format in an industrial country with an already established trauma system. PMID- 26815451 TI - Distinguishing between acute appendicitis and appendiceal mucocele: is this possible preoperatively? AB - PURPOSE: Mucocele of the appendix is an infrequent event, characterized by a cystic dilatation of the lumen. It is often diagnosed clinically from signs and symptoms of acute appendicitis or, if it is asymptomatic, as an incidental finding during ultrasonography, computed tomography, or laparotomy. METHODS: We evaluated the histological data of patients who were believed to have mucocele of the appendix. These patients (n = 23) were compared with sex- and age-matched control subjects (n = 79) with appendicitis. RESULTS: The main reason for emergency surgery was lower right abdominal pain in 15 patients, and intestinal obstruction in three. Univariate analysis using sonography demonstrated that the larger appendiceal outer diameter was positively correlated with the diagnosis of appendiceal mucocele (p = 0.001) and the mean white blood cell count was negatively correlated (p = 0.023). In urine analysis, 41.7 % of the mucocele patients and 10 % of the appendicitis patients had microscopic hematuria, respectively (p = 0.019). An outer diameter of 10 mm or more was predictive of appendiceal mucocele diagnosis, with a sensitivity of 76.5 %, specificity of 81 %, positive predictive value of 76.5 %, and negative predictive value of 94.12 %. The overall diagnostic accuracy was 80.2 %. One point was given for the presence of each of these factors to develop a new score. The resulting area under the receiver operator characteristic curve was 0.855 (95 % CI 0.741-0.969) for the score. The histological examination of the specimens revealed mucocele in 15 cases, mucinous cystadenoma in seven cases and mucinous cystadenocarcinoma in one case. Twenty patients underwent appendectomy, and three patients were treated with right colectomy. CONCLUSIONS: A threshold 10-mm diameter of the appendix under compression is a useful preoperative measurement for differentiating between appendiceal mucocele and acute appendicitis. Microhematuria is simple test that can provide a significant role in supporting the clinical diagnosis of appendiceal mucocele in the emergency department. PMID- 26815453 TI - ESTES News 5_2013. PMID- 26815452 TI - Erratum to: Do cervical spine X-rays for trauma have clinically significant incidental findings? PMID- 26815454 TI - Vocational Rehabilitation of Transition-Age Youth with Disabilities: A Propensity Score Matched Study. AB - Objective To investigate the employment outcomes of vocational rehabilitation (VR) services for youth with disabilities in a targeted, enhanced, and contract based secondary transition program as compared to the traditional VR transition services. Methods A population-based study was conducted on 4422 youth with physical, intellectual, learning, mental and hearing disabilities aged 14-21 at application and whose case was closed after receiving VR transition services in a Midwestern state. Selected youth were classified into either targeted secondary transition program (START) or non-START treatment group. The employment outcomes of the groups were compared using propensity-score matching procedures. Results 2211 youth with disabilities in each treatment group were successfully matched based on demographic characteristics, types of disabilities, existence of severe functional limitations, and year of referral. The overall rehabilitation rate was 57 % [95 % confidence interval (CI) 56-59 %], where the START group rate was 61 % (95 % CI 59-63 %) and the non-START group 53 % (95 % CI 51-55 %). The propensity score matched odds ratio (OR) was 1.40 (95 % CI 1.24-1.58; p < 0.001). Subgroup analyses showed that the odds of rehabilitation in youth with disabilities were consistently higher when they were in START as compared to non-START (OR ranged from 1.27 to 1.92 with p < 0.05 except for the Hispanic subgroup). Conclusion The results suggest that VR services in a targeted, enhanced, and contract-based secondary transition program are more effective in transitioning youth with disabilities to employment than the regular VR transition services. PMID- 26815455 TI - A Thermodynamic Model of Monovalent Cation Homeostasis in the Yeast Saccharomyces cerevisiae. AB - Cationic and heavy metal toxicity is involved in a substantial number of diseases in mammals and crop plants. Therefore, the understanding of tightly regulated transporter activities, as well as conceiving the interplay of regulatory mechanisms, is of substantial interest. A generalized thermodynamic description is developed for the complex interplay of the plasma membrane ion transporters, membrane potential and the consumption of energy for maintaining and restoring specific intracellular cation concentrations. This concept is applied to the homeostasis of cation concentrations in the yeast cells of S. cerevisiae. The thermodynamic approach allows to model passive ion fluxes driven by the electrochemical potential differences, but also primary or secondary active transport processes driven by the inter- play of different ions (symport, antiport) or by ATP consumption (ATPases). The model-confronted with experimental data-reproduces the experimentally observed potassium and proton fluxes induced by the external stimuli KCl and glucose. The estimated phenomenological constants combine kinetic parameters and transport coefficients. These are in good agreement with the biological understanding of the transporters thus providing a better understanding of the control exerted by the coupled fluxes. The model predicts the flux of additional ion species, like e.g. chloride, as a potential candidate for counterbalancing positive charges. Furthermore, the effect of a second KCl stimulus is simulated, predicting a reduced cellular response for cells that were first exposed to a high KCl stimulus compared to cells pretreated with a mild KCl stimulus. By describing the generalized forces that are responsible for a given flow, the model provides information and suggestions for new experiments. Furthermore, it can be extended to other systems such as e.g. Candida albicans, or selected plant cells. PMID- 26815456 TI - [Update on lamellar transplantation surgery of the cornea . Minimally invasive, individualized and protective therapy]. PMID- 26815457 TI - [Psychosomatics in ophthalmology]. PMID- 26815459 TI - 10(th) European Congress of Trauma and Emergency Surgery : May 13-17, 2009 Antalya, Turkey. PMID- 26815458 TI - [Boston-keratoprosthesis : Preliminary experiences in 13 high-risk eyes from the Department of Ophthalmology of the University of Cologne]. AB - BACKGROUND: Corneal transplantation in high-risk eyes remains a challenge. The Boston keratoprosthesis (B-KPro) is a final option for patients with end-stage corneal disease and a poor prognosis with conventional penetrating keratoplasty. In this article the results of the first 13 eyes that received a B-KPro type I at the Department of Ophthalmology, University of Cologne, Germany are reported and the usefulness of postoperative slit-lamp optical coherence tomography (SL-OCT) for control purposes is evaluated. MATERIAL AND METHODS: All recipients of a B KPro type I between September 2013 and May 2015 were included in the study. The feasibility of the operation, clinical outcomes, complications and revision surgery were investigated. The visualization of wound healing by SL-OCT was analyzed. RESULTS: The age of the patients ranged from 26 to 92 years (mean 57.3 +/- 20.9 years). In all 13 eyes from 12 patients (6 males and 6 females) dense corneal opacification with vascularization and sometimes also conjunctivalization was present. Preoperative visual acuity was reduced and ranged from mere light perception up to a maximum of 1/35 eye chart. All 13 eyes could be supplied with a B-KPro type I without any intraoperative complications, in 6 eyes no significant postoperative complications occurred, whereas in 7 eyes various additional surgical interventions were required and 1 B-KPro could not be preserved. Postoperative visual acuity ranged from light perception to 20/32 and was significantly improved in 85 % of the treated eyes. The use of SL-OCT reproducibly allowed the postoperative assessment of stromal thinning. CONCLUSION: The B-KPro provides the possibility of visual rehabilitation in high risk eyes that could never be achieved without artificial cornea replacement. Despite higher complication rates this technique represents a significant progress in the surgical treatment of complex corneal pathologies. Regular and intensive postoperative controls are necessary to achieve good long-term results. PMID- 26814964 TI - The genome of the seagrass Zostera marina reveals angiosperm adaptation to the sea. AB - Seagrasses colonized the sea on at least three independent occasions to form the basis of one of the most productive and widespread coastal ecosystems on the planet. Here we report the genome of Zostera marina (L.), the first, to our knowledge, marine angiosperm to be fully sequenced. This reveals unique insights into the genomic losses and gains involved in achieving the structural and physiological adaptations required for its marine lifestyle, arguably the most severe habitat shift ever accomplished by flowering plants. Key angiosperm innovations that were lost include the entire repertoire of stomatal genes, genes involved in the synthesis of terpenoids and ethylene signalling, and genes for ultraviolet protection and phytochromes for far-red sensing. Seagrasses have also regained functions enabling them to adjust to full salinity. Their cell walls contain all of the polysaccharides typical of land plants, but also contain polyanionic, low-methylated pectins and sulfated galactans, a feature shared with the cell walls of all macroalgae and that is important for ion homoeostasis, nutrient uptake and O2/CO2 exchange through leaf epidermal cells. The Z. marina genome resource will markedly advance a wide range of functional ecological studies from adaptation of marine ecosystems under climate warming, to unravelling the mechanisms of osmoregulation under high salinities that may further inform our understanding of the evolution of salt tolerance in crop plants. PMID- 26815460 TI - Predictors of Atrial Fibrillation Recurrence in Hyperthyroid and Euthyroid Patients. AB - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in adults, and is encountered in 10-15% of the patients with hyperthyroidism. Unless euthyroidism is restored, pharmacological or electrical cardioversion is controversial in patients with AF who remain hyperthyroid. OBJECTIVE: The aim of this study was to assess the efficacy of electrical cardioversion and predictors of AF recurrence in hyperthyroid and euthyroid patients. METHODS: The study included 33 hyperthyroid (21 males) and 48 euthyroid (17 males) patients with persistent AF. The patients were sedated with intravenous midazolam before undergoing electrical cardioversion delivered by synchronized biphasic shocks. Rates of AF recurrence were recorded. RESULTS: Mean follow-up was 23.63 +/- 3.74 months in the hyperthyroid group and 22.78 +/- 3.15 months in the euthyroid group (p = 0.51). AF recurred in 14 (43.8%) and 21 (44.7%) patients in each group, respectively (p = 0.93). Multivariate regression analysis in each group showed that AF duration was the only predictor of AF recurrence, with odds ratios of 1.38 (95% confidence interval [CI] = 1.05 - 1.82, p = 0.02) in the hyperthyroid group and 1.42 (95% CI = 1.05 - 1.91, p= 0.02) in the euthyroid group. CONCLUSION: Rates of long-term AF recurrence were similar in successfully cardioverted hyperthyroid and euthyroid patients. The only predictor of AF recurrence in both groups was AF duration. PMID- 26815462 TI - Association between Functional Variables and Heart Failure after Myocardial Infarction in Rats. AB - BACKGROUND: Heart failure prediction after acute myocardial infarction may have important clinical implications. OBJECTIVE: To analyze the functional echocardiographic variables associated with heart failure in an infarction model in rats. METHODS: The animals were divided into two groups: control and infarction. Subsequently, the infarcted animals were divided into groups: with and without heart failure. The predictive values were assessed by logistic regression. The cutoff values predictive of heart failure were determined using ROC curves. RESULTS: Six months after surgery, 88 infarcted animals and 43 control animals were included in the study. Myocardial infarction increased left cavity diameters and the mass and wall thickness of the left ventricle. Additionally, myocardial infarction resulted in systolic and diastolic dysfunction, characterized by lower area variation fraction values, posterior wall shortening velocity, E-wave deceleration time, associated with higher values of E / A ratio and isovolumic relaxation time adjusted by heart rate. Among the infarcted animals, 54 (61%) developed heart failure. Rats with heart failure have higher left cavity mass index and diameter, associated with worsening of functional variables. The area variation fraction, the E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate were functional variables predictors of heart failure. The cutoff values of functional variables associated with heart failure were: area variation fraction < 31.18%; E / A > 3.077; E-wave deceleration time < 42.11 and isovolumic relaxation time adjusted by heart rate < 69.08. CONCLUSION: In rats followed for 6 months after myocardial infarction, the area variation fraction, E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate are predictors of heart failure onset. PMID- 26815461 TI - Analysis Treatment Guideline versus Clinical Practice Protocol in Patients Hospitalized due to Heart Failure. AB - BACKGROUND: Despite the availability of guidelines for treatment of heart failure (HF), only a few studies have assessed how hospitals adhere to the recommended therapies. OBJECTIVES: Compare the rates of adherence to the prescription of angiotensin-converting enzyme inhibitor or angiotensin II receptor blockers (ACEI/ARB) at hospital discharge, which is considered a quality indicator by the Joint Commission International, and to the prescription of beta-blockers at hospital discharge, which is recommended by national and international guidelines, in a hospital with a case management program to supervise the implementation of a clinical practice protocol (HCP) and another hospital that follows treatment guidelines (HCG). METHODS: Prospective observational study that evaluated patients consecutively admitted to both hospitals due to decompensated HF between August 1st, 2006, and December 31st, 2008. We used as comparing parameters the prescription rates of beta-blockers and ACEI/ARB at hospital discharge and in-hospital mortality. RESULTS: We analyzed 1,052 patients (30% female, mean age 70.6 +/- 14.1 years), 381 (36%) of whom were seen at HCG and 781 (64%) at HCP. The prescription rates of beta-blockers at discharge at HCG and HCP were both 69% (p = 0.458), whereas those of ACEI/ARB were 83% and 86%, respectively (p = 0.162). In-hospital mortality rates were 16.5% at HCP and 27.8% at HCG (p < 0.001). CONCLUSION: There was no difference in prescription rates of beta-blocker and ACEI/ARB at hospital discharge between the institutions, but HCP had lower in-hospital mortality. This difference in mortality may be attributed to different clinical characteristics of the patients in both hospitals. PMID- 26815463 TI - The challenges and advances of polytrauma care in 2012. PMID- 26815464 TI - Polytrauma in the elderly: specific considerations and current concepts of management. AB - With an aging and more active older population, an increased incidence of elderly trauma patients, including severely injured geriatric patients, is anticipated. Poorer functional outcomes and increased mortality and morbidity rates in these patients compared to their younger counterparts may be inevitable due to the associated pre-existing medical conditions and the reduced physiological reserves and compensatory mechanisms secondary to aging. However, mortality and complication rates can be reduced, and outcomes can be improved, when prompt and aggressive treatment is provided. Knowledge of the specific issues, challenges and the distinctive injury patterns of this unique trauma population is important when treating elderly polytrauma patients. In the herein study, the special needs of these patients and the current concepts on their management are summarised. Research in this field is ongoing in order to develop advanced management strategies to optimise outcomes. Overall, these patients should not be treated as "older adults", but as a special population with special considerations and the trauma care should be tailored to meet their specific needs. PMID- 26815468 TI - Reliability of measurement techniques for the hepato-splanchnic region in multiple-trauma patients. AB - PURPOSE: Relevant information on the adequacy of intestinal perfusion is needed. The objective of our study was to investigate the relationship between the difference in intra-mucosal and arterial CO2 pressure (pCO2 gap) and the outcome in multiply injured patients and relations between the pCO2 gap and intestinal permeability (IP). METHODS: Forty consecutive multiply injured patients, admitted to the intensive care unit (ICU) of the University Medical Centre Ljubljana, were studied prospectively. On days 2 and 4, IP was measured using the lactulose mannitol (L/M) test. For 4 days, the pCO2 gap was measured using air tonometry. Multiple organ failure (MOF) scores were calculated daily. RESULTS: No significant differences in the MOF scores and length of ICU stay were found between the groups formed with respect to the presumably normal pCO2 gap value of 1.33 kPa. The baseline pCO2 gap difference in patients with abdominal injuries was significantly (p = 0.01) higher in comparison with those without abdominal injuries. There was no correlation between the pCO2 gap values and L/M index measured simultaneously and also between the baseline and average pCO2 gap and L/M index measured on days 2 and 4. We were unable to find any association between the MOF score and pCO2 gap. The MOF score, however, correlated significantly with the L/M value determined on day 4 (r = 0.85, p = 0.02). The average gastric retention volume was inversely correlated with the average pCO2 gap (r = -0.33, p = 0.04). CONCLUSIONS: The pCO2 gap in trauma patients on intra gastric enteral nutrition in the phase of present technical solutions has no prognostic value for the development of MOF, but IP correlated with it. PMID- 26815467 TI - The treatment of traumatic shock: recent advances and unresolved questions. AB - Uncontrolled bleeding remains a leading cause of potentially preventable death after trauma. Timely, adequate resuscitation in traumatic shock is an essential, lifesaving aspect of polytrauma care. Whilst basic principles in the treatment of traumatic shock remain the same-achieving hemorrhage control and replacing lost volume, the way this is achieved has changed significantly in the last five years. The abandonment of blood pressure driven uncontrolled fluid resuscitation, the introduction of the concept of hemostatic resuscitation, and the increasing use of massive transfusion protocols have all contributed to an improvement in timely access to various blood products. The increase in knowledge regarding the pathophysiology of trauma, the availability of adjuncts, and the array of resuscitation monitoring options available have all contributed to a potentially improved approach to resuscitation. The purpose of this report is to review the most important advances in traumatic shock therapy in the last five years. PMID- 26815465 TI - The Glue Grant experience: characterizing the post injury genomic response. AB - Despite ongoing improvements in resuscitation, care, and outcomes, traumatic injury remains a significant health care and economic burden. The causes are multifactorial, but our approach to the clinical management of these patients remains limited by our current understanding of the pathobiology of the disease. A multicenter, multidisciplinary program known as the "Inflammation and the Host Response to Injury" Large Scale Collaborative Research Program was created by the National Institute of General Medical Sciences (NIGMS, U54 GM062119-10) in 2001 in a 10-year effort to address some of these issues. Its primary goal is to describe the human genomic response to severe trauma and burns, and to examine changes in gene expression in the context of different clinical outcomes. The Program has not only successfully implemented clinical care guidelines for managing the severe trauma patient based on the best available evidence to minimize iatrogenic variability, but it has also examined the genome-wide, immune inflammatory response in total and isolated blood leukocyte populations. This review will address current milestones as well as future directions for the Program. PMID- 26815466 TI - Physiological assessment of the polytrauma patient: initial and secondary surgeries. AB - The timing of fracture fixation in polytrauma patients has been debated for a long time. The decision between DCO (damage control orthopaedics) and ETC (early total care) is a difficult dilemma. Overzealous ETC in haemodynamically compromised patients with significant chest and head injuries can be detrimental. It has been shown, however, that early fracture fixation has a trend towards better outcome in patients with less severe injuries. Delaying all orthopaedic surgery in critically injured patients can be a safe alternative, but has several disadvantages like longer ICU stay and septic complications. The literature shows equivocal evidence for both settings. This article will summarize the historical background and controversies regarding patient assessment and decision making during the treatment of polytrauma patients. It will also give guidance for choosing DCO versus ETC in the clinical setting. PMID- 26815469 TI - Risk factors associated with the development of post-traumatic retained hemothorax. AB - OBJECTIVE: To identify risk factors associated with the development of post traumatic retained hemothorax in chest trauma patients admitted to Hospital San Vicente de Paul (HUSVP). METHODS: This study was a prospective cohort study that included patients with a diagnosis of chest trauma who required a tube thoracostomy as a therapeutic intervention. The measured outcome was retained hemothorax, defined as the presence of blood in the pleural cavity that could not be drained through the initial tube thoracostomy and appeared radio-opaque or hypodense on X-rays or CT scan. The postoperative follow-up period was 30 days. RESULTS: Six hundred thirty-three thoracostomies were performed over a 28-month period for chest trauma; the incidence of post-traumatic retained hemothorax was 16.7%, and additional complications were seen in 10% of cases. The risk of retained hemothorax was associated with: initial blood drainage (median, 400 ml; p < 0.001), the number of tubes placed (two or more; OR = 5.35, CI 95%: 3.98 7.20), the duration of the tube thoracostomy (median, 5 days; p = 0.01), and the need for mechanical ventilation (RR = 2.5, CI 95%: 1.66-3.75). CONCLUSIONS: The risk of post-traumatic retained hemothorax was associated with four factors. The probability of the outcome could be modified by careful monitoring, management protocols, suction through the tube thoracostomy, and maybe an early intervention, such as thoracoscopy. PMID- 26815470 TI - Efficacy and safety of non-operative management of blunt liver trauma. AB - BACKGROUND: The liver is the most frequently affected organ during blunt abdominal trauma. Blunt liver trauma management has changed in the last two decades with the introduction of the computed tomography (CT) scan and non operative management of stable patients. OBJECTIVE: To determine the incidence, efficacy, and failure rate of blunt liver trauma non-operative management as well as the risk factors associated with such treatment in a level 1 trauma center in Colombia. METHODS: We conducted an observational descriptive study on patients with blunt liver trauma who were admitted to a level 1 trauma center in Colombia. The evaluated outcomes were indications of immediate surgical treatment and the success of non-operative management. RESULTS: A total of 73 patients were studied. The most common mechanism of trauma continues to be motor vehicle crashes. In 14 patients (19.2%), immediate surgical intervention was necessary and we observed a Revised Trauma Score (RTS) above 7.8 and intra-abdominal injuries as risk factors. Three patients died (21.4%). Fifty-nine patients (80.8%) received non-operative management, which failed in seven patients (11.2%). Age, severity of liver injury, and intra-abdominal injuries were not risk factors in the failure of non-operative management. Mortality in the non operative management group was 1.7%. CONCLUSION: Non-operative management is the treatment of choice for polytraumatized patients with blunt liver trauma who are hemodynamically stable. Non-operative management is an effective and safe treatment strategy. However, patients with an RTS score under 7.8 and other intra abdominal non-liver injuries are at increased risk for an immediate surgical intervention. PMID- 26815471 TI - Endoscopic thoracic sympathectomy for posttraumatic complex regional pain syndrome. AB - INTRODUCTION: Posttraumatic complex regional pain syndrome (CRPS) has a strongly negative impact on rehabilitation and activities of daily living. Treatment is most often unrewarding. AIM: To analyze the efficacy of endoscopic thoracic sympathectomy (ETS) in reducing pain and disability associated with CRPS prospectively. PATIENT AND METHODS: Over a 5-year period, 12 patients (7 females and 5 males; median age 46.5 [range 34-60 years]) with posttraumatic CRPS underwent unilateral ETS. The median duration of CRPS symptoms before ETS was 3.8 months (range 1.2-19.9). The sympathetic chain was resected from the 2nd to the 5th rib, and the nerve of Kuntz was severed. Median postoperative 16 months (range 12-40). Pain was assessed, at rest (passive) and during movement (active), using a visual analogue scale (VAS) from 0 to 10. RESULTS: One patient (8%) suffered a hydrothorax and 3 patients (25%) complained of contralateral compensatory hyperhydrosis. At 1 month (n = 12), 2 months (n = 7), 6 months (n = 12), and 1 year (n = 12) after ETS, there was a significant decrease in passive and active VAS (P < 0.05). Ten out of the 12 patients (83%) needed fewer analgesics after surgery, and eight (67%) did not need analgesics at all. The median sleep duration improved significantly from a preoperative value of 2 h (range 1-7) to a postoperative value of 6.25 h (range 3.5-8) (P < 0.001). Overall, patient satisfaction was 83%. CONCLUSION: ETS is effective at decreasing pain and improving quality of life, and should therefore be considered in the treatment of CRPS. PMID- 26815472 TI - Introduction of guidelines to facilitate enteral nutrition in a surgical intensive care unit is associated with earlier enteral feeding. AB - PURPOSE: Patients treated postoperatively in surgical intensive care units often receive delayed enteral nutrition. We hypothesized that the introduction of guidelines promoting early enteral nutrition is associated with earlier enteral feeding. METHODS: Enteral nutrition guidelines were created by the consensus of a multidisciplinary team consisting of intensivists, nurses, nutritionists, and surgeons. The guidelines were implemented through repeated staff education. We prospectively compared data on nutritional support in the surgical intensive care unit of a tertiary care center before (pre-intervention period, from January 27 to April 30, 2008) and after (post-intervention period, from May 1st to August 15th, 2008) implementation of the guidelines. The primary outcome was time to enteral feeding (oral or tube feeding). RESULTS: 146 patients were evaluated during the pre-period and 141 patients during the post-period. Patients during the two time periods had similar demographics and clinical characteristics. None of the patients were without nutrition for longer than 7 days. Oral or feeding tube nutrition was started earlier in the post-period (median 1 vs. 2 days, p < 0.001). There was no difference in the percentages of patients receiving parenteral nutrition (7.4 vs. 10%, p = 0.360). There was no increase in aspiration events in the post-period (8 vs. 9.4%, p = 0.606). CONCLUSIONS: Introduction of guidelines to facilitate enteral nutrition in a surgical intensive care unit was associated with earlier enteral feeding. PMID- 26815473 TI - Long-term follow-up of blowout fractures of the orbital floor reconstructed with a polyglactin 910/PDS implant. AB - PURPOSE: Resorbable alloplastic materials are used in many surgical applications. This retrospective study evaluated the clinical outcome after reconstruction of traumatic orbital floor defects using a polyglactin 910/PDS implant (EthisorbTM). PATIENTS AND METHODS: Seventy patients with isolated blowout fractures of the orbital floor resulting in defect sizes of up to 2.5 cm(2) were included in this study. All patients were clinically examined 5 days after surgery at the time of suture removal (T1) and 18 months postoperatively (T2). Diplopia was graded as significant diplopia or diplopia in extreme gaze. RESULTS: At T1, diplopia was observed in 9% of the patients, swelling of the periorbital region in 6%, and enophthalmus in none of the patients. No persistent complications were observed at T2. CONCLUSION: Reconstructive surgery of the orbit is one of the most demanding challenges in maxillofacial surgery. For traumatic defects of the orbital floor, reconstruction using a polyglactin 910/PDS implant (Ethisorb(TM)) seems to be a reliable method for the repair of small-to-moderate defects. PMID- 26815474 TI - Intramedullary femoral nailing through the trochanteric fossa versus greater trochanter tip: a randomized controlled study with in-depth functional outcome results. AB - PURPOSE: In a level 1 university trauma center, an explorative randomized controlled study was performed to compare soft tissue damage and functional outcome after antegrade femoral nailing through a trochanteric fossa (also known as piriform fossa) entry point to a greater trochanter entry point in patients with a femoral shaft fracture. MATERIALS AND METHODS: Nineteen patients were enrolled and randomly assigned to two nail insertion groups; ten patients were treated with an Unreamed Femoral Nail((r)) (UFN, Synthes((r)), Solothurn, Switzerland) inserted at the trochanteric fossa and nine patients were treated with an Antegrade Femoral Nail((r)) (AFN, Synthes((r)), Solothurn, Switzerland) inserted at the tip of the greater trochanter. The main outcome measures were pain, gait, nerve and muscle function, along with endurance. Magnetic resonance imaging (MRI), electromyography (EMG), and Cybex isokinetic testings were performed at, respectively, 2 and 6 weeks and at a minimum of 12 months after surgery. RESULTS: The MRI and EMG showed, in both groups, signs of iatrogenic abductor musculature lesions (four in the UFN group and four in the AFN group) and superior gluteal nerve injury (five in the UFN group and four in the AFN group). The isokinetic measurements and the patient-reported outcomes showed moderate reduction in abduction strength and endurance, as well as functional impairment with slight to moderate interference with daily life in both groups, with no appreciable differences between the groups. CONCLUSIONS: Anatomical localization of the entry point seems to be important for per-operative soft tissue damage and subsequent functional impairment. However, the results of this study did not show appreciable differences between femoral nailing through the greater trochanter tip and nailing through the trochanteric fossa. PMID- 26815475 TI - Health-related quality of life of trauma patients after intensive care: a 2-year follow-up study. AB - PURPOSE: This study aimed to assess the health-related quality of life (HRQOL) in trauma patients 2 years after discharge from an intensive care unit (ICU) in Zunyi, China, and to investigate the possible determinants of HRQOL. METHODS: A total of 436 trauma patients treated in the ICU were followed up for 2 years. The Medical Outcomes Study Short Form 36 (SF-36) was used to measure the quality of life 1 and 2 years after their discharge. RESULTS: After a 2-year follow-up, there were, in total, 347 (79.6%) survivors. From 1 to 2 years after discharge, the HRQOL improved in one physical health domain and three mental health domains. Logistic regression showed that female patients had lower mental component summary (MCS) scores (odds ratio [OR] = 1.9, 95% confidence interval [CI]: 1.2 3.0). Patients older than 40 years had lower scores in the physical component summary (PCS) (OR = 1.7, 95% CI: 1.1-2.7). Patients who stayed in the ICU for longer than 7 days had lower PCS scores (OR = 1.6, 95% CI: 1.0-2.5). The association between head injury and low MCS scores was statistically significant (OR = 1.8, 95% CI: 1.1-2.9). Patients with an Injury Severity Score (ISS) > 24 had lower scores in the PCS (OR = 1.9, 95% CI: 1.2-3.1). CONCLUSIONS: The HRQOL of a group of Chinese trauma patients after ICU treatment improved from 1 to 2 years after discharge. Age, sex, length of ICU stay, ISS, and existence of head injury were associated with physical or mental HRQOL after discharge. Further studies with more measurements and larger sample sizes are still warranted. PMID- 26815476 TI - Mesenchymal stem cell (MSC) and endothelial progenitor cell (EPC) growth and adhesion in six different bone graft substitutes. AB - INTRODUCTION: Several different synthetic and allograft bone graft substitutes are used clinically to treat large bone defects. In contrast to the "gold standard" of autologous bone grafts, these do not contain bone-forming (MSC) or vessel-forming (EPC) cells. In order to achieve the same level of success enjoyed by autologous bone grafts, they must be compatible with mesenchymal stem cells (MSC) and endothelial progenitor cells (EPC). In a previous study, we seeded MSC onto six different bone graft substitutes and then measured the cell adhesion, viability, differentiation, and morphology. In the present study, we seeded both MSC and EPC onto the same six bone graft substitutes and measured the same parameters. METHODS: In vitro, 125,000 MSC and 125,000 EPC were seeded onto Chronos((r)), Vitoss((r)), Actifuse((r)), Biobase((r)), Cerabone((r)), and Tutoplast((r)). Cell adhesion (fluorescence microscopy) and viability (MTT assay) were measured on days 2, 6, and 10. Osteogenic (cbfa-1, alkaline phosphatase [ALP], osteocalcin, collagen-1 alpha [Col1A]) and endothelial (von Willebrand factor [vWF], vascular endothelial growth factor [VEGF], kinase domain receptor [KDR]) gene expression were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). Morphology was described by scanning electron microscopy (SEM) at day 2. RESULTS: MSC adhered significantly better to Tutoplast((r)), Chronos((r)), Actifuse((r)), and Biobase((r)). EPC adhered better to Actifuse((r)), Chronos((r)), Biobase((r)), and Tutoplast((r)). Viability increased over time when seeded on Tutoplast((r)) and Chronos((r)). Osteogenic and endothelial gene expression were detectable at day 10 in cells seeded on Chronos((r)), Actifuse((r)), and Tutoplast((r)). The best morphology of MSC and EPC was found on Tutoplast((r)), Chronos((r)), Actifuse((r)), and Biobase((r)). CONCLUSION: When bone graft substitutes are used to help fill large defects, it is important that their interaction with these cells be supportive of bone healing. PMID- 26815477 TI - Effects on the ubiquitin proteasome system after closed soft-tissue trauma in rat skeletal muscle. AB - Previous studies have suggested that an increased catabolic stage of skeletal muscle in pathological situations is mainly a reflection of ubiquitin-proteasome system-controlled proteolysis. The proteolytic mechanisms that occur after local muscle trauma are poorly defined. We investigated the effects of closed soft tissue trauma on ubiquitin-proteasome dependent protein breakdown in rats (n = 25). The enzymatic activities of the ubiquitination and proteasome reactions were both reduced (p < 0.05) immediately after contusion of the hind limb musculus extensor digitorum longus. The same effect was observed in extracts of lung tissue from the injured animals. Cellular levels of free and protein-conjugated ubiquitin were significantly elevated upon decreased proteolytic activity. Our data support an early-state anti-proteolytic role of the ubiquitin-proteasome pathway after local injury. This further implies that there is a yet-to-be elucidated complex regulatory mechanism of muscle regeneration that involves various proteolytic systems. PMID- 26815478 TI - Effective teaching modifies medical student attitudes toward pain symptoms. AB - INTRODUCTION: Recent studies have raised the question of whether last year medical students and first year residents show an adequate attitude toward their patient's pain as reflected by prescribed pain medication. Underuse of analgetics could be demonstrated in several studies even after a correct diagnosis of pain was made and has led to the term "oligoanalgesia." Our study was aimed at evaluating the potential of improving student attitudes toward pain by changing the curriculum during the last year of medical education. METHODS: The study was designed as a prospective, randomized controlled, blinded cohort study. A recent change by law (2002) in the official curriculum ("Approbationsordnung") made it possible to compare two groups of last year medical students who were trained in different curricula during a 1-year transitional period. One group received special training on various aspects of pain and analgesic therapy (new curriculum), while the other group followed the conventional curriculum (old curriculum) without further special training. Both students and examiners were blinded toward the study target. Measurement parameters were a clinical experiment with standardized patients (OSCE) and a key features test. RESULTS: The study shows a considerable improvement of attitude toward pain in those students undergoing the new curriculum. This group demonstrated better OSCE results and significant improvement in key features tasks, and also outperformed the old curriculum group in the choice of analgesia. DISCUSSION: Our results confirm the importance of humanistic attitudes in future doctors in addition to the traditional implementation of knowledge and skills. Changes in the medical curriculum can positively influence these attitudes. PMID- 26815479 TI - The use of cerclage wires as a suture passer in the repair of quadriceps tendon ruptures. AB - We describe a novel, simple and cost-effective method of passing sutures through the patella, without the need for expensive or specialised equipment. PMID- 26815480 TI - Partial liver herniation into the right chest following trauma: a delayed presentation as acute injury managed by laparoscopically assisted mini thoracotomy. AB - INTRODUCTION: Traumatic diaphragmatic rupture is a relatively uncommon occurrence, with an incidence of 0.8-5% reported in the literature. The reported percentage of missed diaphragmatic injuries that were discovered later ranges from 12 to 66%. Herniation of the liver through the right diaphragm has been reported in the literature after liver transplantation, and in trauma populations. MATERIALS AND METHODS: Here, we report a case of late identification of partial liver herniation into the right chest (8 years post initial injury), due to a recent motor vehicle crash. Thought to be suffering from an acute injury, the patient was taken to the operating room and a laparoscopically assisted mini-thoracotomy was performed. An old diaphragmatic injury was found intraoperatively; laparoscopically assisted mini-thoracotomy was used to repair the diaphragm, and the liver was returned into the abdomen. CONCLUSION: Right sided diaphragmatic laceration, if diagnosed at the time of injury, may be repaired with the minimally invasive technique we describe here. PMID- 26815483 TI - Focus on Emergency Surgery of the Pancreas. PMID- 26815481 TI - T Cell Receptor Mediated Calcium Entry Requires Alternatively Spliced Cav1.1 Channels. AB - The process of calcium entry in T cells is a multichannel and multi-step process. We have studied the requirement for L-type calcium channels (Cav1.1) alpha1S subunits during calcium entry after TCR stimulation. High expression levels of Cav1.1 channels were detected in activated T cells. Sequencing and cloning of Cav1.1 channel cDNA from T cells revealed that a single splice variant is expressed. This variant lacks exon 29, which encodes the linker region adjacent to the voltage sensor, but contains five new N-terminal exons that substitute for exons 1 and 2, which are found in the Cav1.1 muscle counterpart. Overexpression studies using cloned T cell Cav1.1 in 293HEK cells (that lack TCR) suggest that the gating of these channels was altered. Knockdown of Cav1.1 channels in T cells abrogated calcium entry after TCR stimulation, suggesting that Cav1.1 channels are controlled by TCR signaling. PMID- 26815482 TI - Key Factors Affecting Reproductive Success of Thoroughbred Mares and Stallions on a Commercial Stud Farm. AB - To evaluate factors contributing to fertility of thoroughbred mares, data from 3743 oestrous periods of 2385 mares were collected on a large thoroughbred farm in Ireland. Fourteen stallions (mean age 8.3 years; range 4-15 years) had bred 2385 mares (mean age 9.4 years; range 3-24 years). Maiden mares accounted for 12%, mares with a foal at foot for 64%, and barren, slipped or rested mares for 24% of the total. The mean pregnancy rate per cycle was 67.8% (68.6% in year 1 and 66.9% in year 2). Backward stepwise multivariable logistic regression analysis was utilized to develop two models to evaluate mare factors, including mare age, reproductive status, month of foaling, dystocia, month of cover, foal heat, cycle number, treatments, walk-in status and stallion factors including stallion identity, stallion age, shuttle status, time elapsed between covers and high stallion usage on the per cycle pregnancy rate and pregnancy loss. Old age (p < 0.001) and cover within 20 days post-partum (p < 0.003) were associated with lowered pregnancy rates. High mare age (p < 0.05) and barren, slipped or rested reproductive status (p = 0.05) increased the likelihood of pregnancy loss. Uterine inflammation or infection, if appropriately treated, did not affect fertility. Only high usage of stallions (used more than 21 times in previous week) was associated with lowered (p = 0.009) pregnancy rates. However, shuttle stallions were more likely to have increased (p = 0.035) pregnancy survival, perhaps reflecting a bias in stallion selection. In conclusion, mare age exerted the greatest influence on fertility; nonetheless, thoroughbreds can be effectively managed to achieve high reproductive performance in a commercial setting. PMID- 26815484 TI - Pancreatic Trauma Revisited. AB - Pancreatic trauma is rare with an incidence between one and two percent in patients with abdominal trauma. Morbidity and mortality, however, are significant with rates approaching 40-45% in some reports. The majority of patients with injuries to the pancreas have associated trauma to other organs which are primarily responsible for the high mortality rate. The continuity of the main pancreatic duct is the most important determinant of outcome after injury to the pancreas. If there is no evidence of ductal injury on fine-cut CT or on ERCP, nonoperative management is chosen. The indications for operative management are as follows: (1) peritonitis on physical examination; (2) hypotension and a positive FAST; and (3) evidence of disruption of the pancreatic duct on fine-cut CT or on ERCP. After exposure and evaluation of the extent of injuries to the pancreas and duodenum, a decision must be made on the procedure. For pancreatic contusions, hematomas, or small lacerations, simple external drainage or pancreatorrhaphy with drainage can be performed. For ductal transection at the neck, body, or tail, the procedure of choice is a distal pancreatectomy or Roux en-Y distal pancreatojejunostomy. If the patient has suffered a ductal transection at the head of the pancreas without injury to the duodenum, a Roux-en Y distal pancreatojejunostomy or anterior Roux-en-Y pancreatojejunostomy is the operation of choice. For combined pancreatoduodenal injuries, the options are repair and drainage, diversion via a pyloric exclusion procedure, or pancreatoduodenectomy. Complications of pancreatic injuries include fistulas and intra-abdominal abscesses, and an occasional pancreatic pseudocyst. Key Words. PMID- 26815485 TI - Abdominal Compartment Syndrome in Severe Acute Pancreatitis - When to Decompress? AB - Intra-abdominal hypertension is increasingly reported in patients with severe acute pancreatitis, and is caused by several factors, including visceral edema and ascites associated with massive fluid resuscitation, paralytic ileus and retroperitoneal inflammation. There is a strong relation with early organ dysfunction and mortality in these patients, which makes intraabdominal hypertension an attractive target for intervention. Several reports conclude that this phenomenon occurs within the first 5 days after admission, and that the kinetics of IAH is important: patients with persistent IAH seem to be at the highest risk for mortality. Several strategies to reduce IAP have been developed, and given the pathophysiology, percutaneous drainage of ascites is a first logical step. However, if conservative measures fail to reduce IAP in a setting with ongoing or worsening organ dysfunction, abdominal decompression is recommended. PMID- 26815486 TI - Open Abdomen after Severe Acute Pancreatitis. AB - The need for surgical decompression for abdominal compartment syndrome is becoming more frequent in patients with severe acute pancreatitis, especially in association with massive fluid resuscitation at the early stages of the disease. Decompression can be achieved with either a full-thickness laparostomy that can be performed through a vertical midline or transverse subcostal incision, or by performing a subcutaneous linea alba fasciotomy. Following a fullthickness laparostomy the open abdomen can be best managed with some form of negative abdominal pressure dressing. During dressing changes every 2-3 days, every attempt should be made to gradually close the fascial incision starting from edges, but avoiding recurrent abdominal compartment syndrome. Gradual closure is more likely to succeed in association with a negative fluid balance. Peripancreatic exploration or necrosectomy is seldom required at the initial laparostomy, unless performed for late onset abdominal compartment syndrome associated with infected peripancreatic necrosis. Primary fascial closure should always be attempted. If impossible and there is no need for subsequent abdominal re-exploration, the open wound should be covered with split-thickness skin grafting directly over the bowel loops. After a maturation period of 9-12 months definitive repair of the abdominal wall defect is performed utilizing the components separation technique, mesh repair, or a pedicular or microvascular tensor facia lata flap. Knowledge of the available decompression and reconstruction options is essential for individualized management of patients with severe acute pancreatitis and abdominal compartment syndrome. More research and comparative studies are needed to determine the most successful methods to be used. PMID- 26815487 TI - Evaluation of Factors Delaying Discharge in Acute Orthopedic Wards: a Prospective Study. AB - INTRODUCTION: Prolonged hospitalization due to delayed discharge not only increases cost, it also increases the risk of medical complications e.g., hospital acquired infections. Length of stay (LOS) is one of the indicators that reflect total cost of care during hospitalization. The study was planned to evaluate the factors affecting delay in discharges from hospital and whether these factors are avoidable. HYPOTHESIS: The LOS in an acute orthopedic trauma ward is mainly determined by relative contribution patient derived factors which are present even prior to admission, rather than organisational/administrative factors. MATERIALS AND METHODS: Four hundred and fifty-three case notes were reviewed for 6 months prospectively from an acute care hospital. Information was collected on demographic profile, functional and cognitive function, past medical and social history, admitting diagnosis, discharge limiting and delaying factors. RESULTS: Out of 453 patients admitted from Jan 2005 to Jun 2005, 50 patients stayed longer than 28 days in the study group. The mean ages of the patients were 84 years (SD 4.5). The mean Abbreviated mental test score of the study was 5 (range 1-10). On admission, 78% of the patients had co-morbidities with 40% of patients having three or more associated medical problems. The two main factors limiting discharge were social issues in 33 patients (66%) and sepsis in 14 patients (28%). CONCLUSION: Older patients with co-morbidities are more prone to long stay due to de-conditioning requiring social input and nosocomial infection. The study thus proved the hypothesis and suggested that early identification of social issues and prompt discharge planning helps to avoid delay in discharge. PMID- 26815488 TI - Osteosynthesis of Proximal Humeral Fractures with the Fixed Angle PHILOS-plate. AB - In a retrospective study we analyzed the functional and radiological outcome of 30 proximal humeral fractures, treated by PHILOS-plate, a fixed-angle device. Two of them were characterized as type Neer III, 14 as type Neer IV, 5 as type Neer V and 9 as type Neer VI. There were 2 2-part, 16 3-part and 12 4-part fractures. According to the constant-score, the normalized constant-score and the UCLA score, good to excellent results were obtained in 66.7, 76.7 and 76.7%. Twenty six (86.7%) patients had no or mild pain. Active forward flexion and active abduction over 90 degrees was possible in 26 (86.7%) cases. Four (13.3%) patients developed partial avascular necrosis. Screw perforation was seen in 3 (10%) cases, delayed union in 1 (3.3%) case, malunion in 1 case and a loosening of plate and screws in another one. A secondary varus displacement of 5 degrees 35 degrees with a mean of 7 degrees was found in 19 (63.3%) cases. The average time to union was 75 days. Fixation with PHILOS-plate is an adequate treatment for displaced 2- to 4-part fractures. Even in dislocated or 4-part fractures or in patients over 65 years good to excellent results were seen in the majority of cases. PMID- 26815489 TI - A Combined Repair Technique for Early Neglected Achilles Tendon Ruptures. AB - OBJECTIVE: This study presents the long-term results of a combined technique, using both Duthie's biological repair and a plantaris tendon transfer for the reconstruction of early neglected tendo Achilles ruptures. MATERIALS AND METHOD: Between January 2000 and November 2004, nine patients with an early neglected Achilles tendon rupture (>= 4 and <= 12 weeks from injury), underwent surgical reconstruction. Eight patients were male and one female, their age was average 41 years and the median follow-up period was 3.66 years. The average clinical defect of the Achilles tendon was 4.33 cm. RESULTS: All patients were examined by the clinical ankle scoring system of Leppilahti et al. (Clin Orthop 346:152-161, 1998). Six patients presented excellent results and three patients had good results. All patients had equal plantarflexion and dorsiflexion with the healthy side and all of the study's patients returned to work 3 months postoperatively. An average muscle atrophy of 0.83 cm was documented compared with the uninjured side. Only four of nine patients (44.44%) had a normal one-legged jump. There were no complications postoperatively and no re-ruptures of the Achilles tendons. CONCLUSION: This combined method appears to be safe and effective, with a low risk for complications, allowing us to obtain excellent results for the majority of our patients. PMID- 26815490 TI - K-wire Arthrodesis and Coracoclavicular Augmentation of Complete Acromioclavicular Separations: Functional and Subjective Results. AB - BACKGROUND: In recent years, there has been a trend from operative to conservative management of complete acromioclavicular separations. Despite this, surgical treatment is still recommended to manual workers and athletes, who account for a large part of the patients. The objective of this study was to evaluate the functional outcome of type III separations according to Tossy managed by temporary arthrodesis of the acromioclavicular joint combined with coracoclavicular augmentation. Special attention was paid to sport exercising patients. PATIENTS AND METHODS: In this study, 32 patients (mean age 39 years) with a complete acromioclavicular separation were investigated. All of them underwent a surgical treatment managed by temporary acromioclavicular arthrodesis with two parallel k-wires and augmentation of the coracoclavicular ligaments with a biodegradable cord (PDS). Functional outcome was assessed after an average follow-up of 36 months by using the Constant-Murley-, Neer- and DASH-score. Additionally, incidence of complications and subjective results were observed. RESULTS: Evaluation of the data, obtained from the scores, revealed an excellent result for the Constant-Murley- and DASH-score for 84% of the patients. Regarding the Neer-score, 78% had an excellent outcome. Eighty-four percent of the patients assessed revealed an excellent to fair subjective result. Cosmetic reasons were most frequently the cause for discontentedness. Minor complications occurred in three patients without severe sequelae. All patients returned back to former working and sport activity level. CONCLUSION: Surgical treatment of complete acromioclavicular separations by temporary arthrodesis with two k-wires and coracoclavicualar PDS-augmentation results in good to excellent function. It is associated with a low complication rate and a high patient contentedness. Particularly for athletes in non-contact sports this surgical technique can still be recommended. PMID- 26815491 TI - Long Term Outcomes after Arthroscopic Management of Tibial Plateau Fractures. AB - OBJECTIVES: Tibial plateau fractures are efficiently treated using arthroscopy when limited to one condyle. Operative technique and early results are now well documented. However, long term results have not been widely reported. The goal of this study was to evaluate clinical and radiological outcomes of arthroscopically treated tibial plateau fractures in the long term. METHODS: Fourteen out of thirty consecutive cases have been reviewed after more than 4 years post-op (4 to 8 years). The SF8 quality of life score and both IKS and Rasmussen knee function scores have been quoted. Radiological analysis looked at Resnick and Niwoyama osteoarthritis score. RESULTS: Functional knee scores at follow-up were 28.0 (Rasmussen) and 187.4 (IKS) in average. The average SF8 score was 4.64. The SF8 score did not correlated with Rasmussen and IKS scores, but with age. Radiological signs of osteoarthritis were noted in 50.0% of cases, with no relationships with the clinical status. CONCLUSIONS: Comparisons with historical long-term studies regarding open reduction and internal fixation show similar outcomes. No specific secondary degenerative problem would alleviate the advantages of the arthroscopic management of tibial plateau fractures in the early post-operative period. PMID- 26815492 TI - Early Results of Scapular Fractures Treated Operatively at a Level One Trauma Center. AB - INTRODUCTION: Certain scapular fractures are best treated with open reduction to restore form and function to the glenohumeral joint. The purpose of this study was to review the results of operative treatment of scapular fractures at a level one trauma center. PATIENTS AND METHODS: Twenty-one cases of operatively treated scapular fractures over a four-year period were identified after a database query. Nine patients had inadequate follow-up and one had a reinjury excluding a total of ten patients from our analysis. This left 11 patients (eight male and three female) with displaced scapular neck and glenoid fractures who were the subjects of this retrospective study. There were no ipsilateral clavicular fractures. The average age was 33.8 years (range, 22-49). Fixation was achieved using titanium 3.5 reconstruction plates and screws in all cases. Three plates were used in one patient and two in the other ten patients. Functional outcomes were assessed by the UCLA shoulder scoring scale at a mean follow-up of 24.0 months. RESULTS: At latest follow-up, nine of the patients had returned to work. Two patients had excellent results, six had good results, two had fair results, and one patient had a poor result. The poor result was associated with a suprascapular neuropathy diagnosed preoperatively. The average UCLA score was 29.1 out of 35 points. DISCUSSION: Open reduction and internal fixation is associated with anatomic reduction, a low complication rate, and satisfactory functional results at short-term follow-up. PMID- 26815493 TI - Bioactive-Coated Implants in Trauma Surgery. AB - Complications still occur in musculoskeletal surgery despite improvements in operating techniques and optimization of implants. Problems include delayed fracture healing, non-unions and extensive osseous infections. Growth factors for local application are in clinical use, but have not become widely accepted. Reasons may be that these proteins are expensive and of limited availability and considerable quantities have to be implanted locally. Coated implants incorporating active ingredients could release drugs locally and thereby generate a high concentration directly in the area of interest without systemic side effects. Compounds that could be used in this way include growth factors for the improvement of fracture healing and antibiotics for prophylaxis of implant related infections. The biodegradable poly(D,L-lactide) coating of implants can facilitate the local controlled release of incorporated growth factors directly into the fracture and thus serves both as a fracture stabilization device and as a carrier for active components. This review presents different models (fracture healing; intervertebral fusion; infection model) demonstrating the efficiency of the coating technology. These findings seem to justify the transfer of this technology into clinical settings. In a preliminary study, gentamicin-coated intramedullary tibial nails were implanted in patients exhibiting fractures with severe soft tissue damage. The preliminary findings do not allow conclusions to be drawn in respect of therapy of fractures with severe soft tissue damage or revision surgery. However, the coating seems to be suitable as a "key technology" for the incorporation of active ingredients and might be helpful in revision arthroplasty. PMID- 26815494 TI - When Should Open Reduction and Internal Fixation Ankle Fractures Begin Weight Bearing? A Systematic Review. AB - The objective of this paper was to review the literature to assess when open reduction and internal fixation ankle fractures should commence weight bearing for the best outcome. An electronic search was undertaken of the databases AMED, Cinahl, Embase, Medline (via Ovid), Pedro and Pubmed, from their inception to November 2005. References lists were scrutinised and a hand search was also performed. We included all English language, human subject, controlled clinical trials, comparing the effects of early against later weight bearing following open reduction and internal fixation of ankle fractures. Two reviewers independently assessed the methodological quality of the literature using the PEDro (Physiotherapy Evidence Database) scoring system. Five papers comprising of 366 ankle fractures were reviewed. Overall, there was no significant difference between commencing early, compared to later weight bearing in subjects following open reduction and internal fixation, when evaluated against function, pain, range of movement, radiological assessment, complications, and return to work. The evidence reviewed was generally poor, with numerous methodological design limitations. The literature suggested that were was little difference between encouraging early or delayed weight bearing after open reduction and internal fixation of ankle fractures. Neither early nor later weight bearing significantly improves or jeopardises outcomes. However, due to the plethora of methodological limitations and limited evidence, it is not possible to reference this conclusion with conviction. Further large, well-designed randomized controlled trials are required to evaluate this area. PMID- 26815495 TI - Clostridium septicum Infection Associated with Necrotizing Pancreatitis, Transmural Gastric Necrosis, and Liquefaction of the Spleen. AB - Spontaneous infection with Clostridium septicum (C. septicum) is rare, but when isolated it is commonly associated with malignancy. We report a case of a 47-year old man with infected pancreatic necrosis involving greater than 80% of the pancreas, transmural gastric necrosis, and liquefaction necrosis of the spleen. Initial cultures revealed C. septicum infection. He was managed with prompt aggressive surgical debridement, resection, appropriate broad spectrum antibiotics, and early enteral nutrition. PMID- 26815496 TI - Tibial Nailing During Pregnancy: A Safe Option. AB - We present a case of a distal tibial fracture in a pregnant patient treated with an intermedullary device. The risks associated with operative treatment of fractures in pregnancy are discussed. The patient underwent a successful procedure using a novel tibial nail which reduced both operative time and radiation exposure. Surgical intervention allowed the mother to have a normal delivery. The patient had an excellent outcome with no adverse effects reported by either mother or baby. PMID- 26815497 TI - Bilateral Avulsion Fractures of the Tibial Tuberosity: A Double Case for Open Reduction and Fixation. AB - Tibial tuberosity fractures are rare and occur mainly in adolescent males during vigorous quadriceps contraction. So far, only ten simultaneous bilateral fractures have been reported. We report the case of a 16-year-old male who avulsed both tibial tuberosities when he landed on his feet after a gymnastics routine. Diagnostic imaging demonstrated Ogden Type IIIA fractures. He underwent bilateral open reduction and screw fixation with a good functional result after 3 months. While closed reduction and percutaneous fixation has been proposed by some, the intraoperative findings in our patient would have prevented correct adaptation of the fragments because of a flap of periosteum impinged in both fracture gaps. This case emphasizes that minimally invasive techniques may sometimes be inappropriate in the management of these types of fractures. PMID- 26815498 TI - Anterior Dislocation of the Hip Associated with an Actebular Fracture: Case Report. AB - Anterior hip joint dislocation is less common than posterior dislocation. Although fractures of the acetabulum can occur in anterior hip dislocations, they are infrequently. In this article, we report an uncommon lesion in a woman who sustained an anterior dislocation of the hip associated with a fracture of the acetabular wall. Close reduction was performed immediately the initial injury. The patient underwent open reduction and internal fixation since the hip joint was result unstable and the CT scan showed the presence of a bone fragment of the anterior acetabular wall. At 2-year follow-up, the clinical and radiological results are excellent. PMID- 26815499 TI - Late Recognized Vascular Injury after High-energy Fracture of the Proximal Tibia: a Pitfall to Know in Current Practice. AB - Failure to recognize associated soft-tissue injuries after high-energy proximal tibia fractures is not uncommon. Despite the progress in managing these complex injuries, a prompt diagnosis of associated arterial injuries still remains difficult. A high index of suspicion for arterial damages is nevertheless mandatory in these severe fractures. Treatment protocols have been developed to reduce the previously reported high rates of amputation and permit an optimal management of soft-tissue and an acceptable functional outcome. We report here a well-documented case of a severely displaced proximal tibia fracture that illustrates the problem of diagnosing and managing the associated vascular injuries. PMID- 26815500 TI - Antioxidative Metabolites Synthesized by Marine Pigmented Vibrio sp. and Its Protection on Oxidative Deterioration of Membrane Lipids. AB - Bacterial strain Vibrio sp. (PIGB 184) isolated from water samples of the Arabian Sea and identified through 16S rRNA demonstrated the production of pigmentary antioxidants with higher ABTS activities 90.9 +/- 0.42 % in comparison with the standard commercial pigmented antioxidant, quercetin 88.8 +/- 1.4 %. Antioxidative metabolites of this strain substantially inhibit the lipid peroxidation (LPO) reactions tested in sheep liver and brain. The antioxidant compounds produced by the Vibrio sp. (PIGB 184), analysed by GC-MS, reveals that it is composed mostly of phenol, 2,4-bis(1,1-dimethylethyl) and pyrrolo[1,2 a]pyrazine-1,4-dione,hexahydro-3-(2-methylpropyl). The interrelationship assessed between LPO and the phenolic compounds showed significant correlation with anti LPO properties (R (2) = 0.9698 to 0.9861). These compounds are responsible for obstruction of harmful radical associated biochemical reactions in biological systems. Pigmented metabolites also tested for attributive biological properties against pathogenic bacteria showed prominent inhibition towards Gram-positive organisms (31.25 to 62.5 MUg ml(-1)). From this study, it may be suggested that the marine bacterium PIGB 184 could be used as a potential bio-resource for antioxidants and needs to be worked out for mass production. PMID- 26815501 TI - Erratum to: Decreased expression of MEG3 contributes to retinoblastoma progression and affects retinoblastoma cell growth by regulating the activity of Wnt/beta-catenin pathway. PMID- 26815503 TI - SUSD2 is frequently downregulated and functions as a tumor suppressor in RCC and lung cancer. AB - Sushi domain containing 2 (SUSD2) is type I membrane protein containing domains inherent to adhesion molecules. There have been few reported studies on SUSD2, and they have mainly focused on breast cancer, colon cancer, and HeLa cells. However, the expression and function of SUSD2 in other cancers remain unclear. In the present study, we conducted an integrated bioinformatics analysis based on the array data from the GEO database and found a significant downregulation of SUSD2 in renal cell carcinoma (RCC) and lung cancer. Western blotting and quantitative RT-PCR (qRT-PCR) confirmed that SUSD2 was frequently decreased in RCC and lung cancer tissues compared with the corresponding levels in normal adjacent tissues. The restoration of SUSD2 expression inhibited the proliferation and clonogenicity of RCC and lung cancer cells, whereas the knockdown of SUSD2 promoted A549 cell growth. Our findings suggested that SUSD2 functions as a tumor suppressor gene (TSG) in RCC and lung cancer. PMID- 26815504 TI - SHh-Gli1 signaling pathway promotes cell survival by mediating baculoviral IAP repeat-containing 3 (BIRC3) gene in pancreatic cancer cells. AB - The abnormally activated hedgehog (Hh) signaling pathway is involved in the regulation of proliferation and apoptosis in pancreatic cancer cells, while its exact molecular mechanism is not clear. The purpose of this study was to investigate the regulatory effect of Hh signaling pathway on the transcription of BIRC3 gene and its underlying mechanism in pancreatic cancer cells, as well as the relationship between the Gli1-dependent BIRC3 transcription and cell survival. Firstly, we examined the effect of knockdown or overexpression of Hh on BIRC3 messenger RNA (mRNA) expression by real-time RT-PCR. Then, the regulatory mechanism of Gli1 to BIRC3 gene transcription was investigated by XChIP-PCR and luciferase assays. Finally, the cell survival mediated by the Gli1-dependent BIRC3 transcription was studied by MTT and annexin V-FITC/propidiumiodide (PI) assays. We found that the expression level of BIRC3 mRNA was positively correlated to SHh/Gli1 signaling activation in three pancreatic cancer cell lines. The XChIP-PCR and luciferase assays data showed that the transcription factor Gli1 bound to some enhancers within the promoter regions of BIRC3 gene and promoted gene transcription. The cell proliferation was increased significantly by SHh/Gli1 expression while the apoptotic rate was reduced under the same condition. Moreover, BIRC3 knockdown inhibited cell proliferation and survival induced by SHh overexpression. Our study reveals that Gli1 promoted transcription of BIRC3 gene via cis-acting elements and the SHh-Gli1 signaling pathway maintained cell survival partially through this Gli1-dependent BIRC3 model in pancreatic cancer cells. PMID- 26815502 TI - MiR-608 rs4919510 is associated with prognosis of hepatocellular carcinoma. AB - Single nucleotide polymorphisms (SNPs) within microRNAs (miRNAs) are considered potential markers for risk and prognosis of various cancers. In the current study, we aimed to determine whether miR-608 rs4919510 affected hepatocellular carcinoma (HCC) prognosis. We genotyped rs4919510 using DNA from blood samples of 362 HCC patients receiving surgical resection of HCC tumor. Associations between rs4919510 and overall survival (OS) and demographic characteristics and clinical features were estimated using the Cox proportional hazards model. Results showed that HCC patients who carried the rs4919510 CC genotype had a significantly longer OS compared to those who carried the GG genotype (P = 0.013, hazard ratio [HR] = 0.600, 95 % confidence interval [CI] 0.402-0.897) and the CG + GG genotype (P = 0.033, HR = 0.681, 95 % CI 0.479-0.970) in univariate analysis. Similar results were obtained in multivariate analysis. Further stratification analysis indicated that rs4919510 was significantly associated with OS in patients who were satisfied with one of the following criteria: male gender, HbsAg-positive, alpha-fetoprotein (AFP)-positive, tumor size >5 cm, cirrhosis, solitary tumor, I + II pTNM stage, or no tumor capsule. Finally, a significantly higher frequency of rs4919510 CC genotype was observed in patients with cirrhosis (22.9 %, 55/240) than those without cirrhosis (14.0 %, 17/121) (P = 0.047). In conclusion, our results illustrated the potential role of miR-608 rs4919510 as a prognostic marker for HCC patients undergoing surgical resection of the tumor. PMID- 26815505 TI - Elevated STMN1 promotes tumor growth and invasion in endometrial carcinoma. AB - Overexpression of stathmin (STMN1) is closely linked to tumor metastases and poor prognosis in endometrial carcinoma (EC). However, the underlying mechanism is little known. In the present study, we investigated the expression of STMN1 in EC. Subsequently, we assessed the role of STMN1 in EC cell proliferation and migration. Our data show that STMN1 is upregulated in EC, and elevated expression of STMN1 is correlated positively with tumor stage and lymph node metastasis. In vitro, forced expression of STMN1 promoted cell invasion and migration. In contrast, knockdown of STMN1 inhibited cell aggressive behaviors. Moreover, the expression and the activity changes of matrix metalloproteinases (MMP)-2/9 were observed in EC cells after the cells being silenced or overexpression of STMN1. In conclusion, STMN1 is an oncogene and it enhances the growth and invasion of EC possibly by mediating the secretion and activation of MMP2 and MMP9 protein. PMID- 26815506 TI - Curcumin analogue, A13, exhibits anti-leukemia effect via inhibiting STAT3. AB - Abnormal activation of signal transducer and activator of transcription 3 (STAT3) was reported in some leukemia, and inhibition of STAT3 can be the strategy for the leukemia treatment in clinic. In this study, we tested the anti-tumor effect of compound A13, a water-soluble analogue of curcumin, in vitro and in vivo. Herein, we show that A13 was able to reduce the viability of mastocytoma (P815 cells) and reticulum cell sarcoma (A20 cells) as measured by MTS assay. This effect was accompanied by a marked increase in the proportion of apoptotic cells as measured by flow cytometry. Furthermore, Western blot analysis suggested that the anti-leukemia effect of A13 was realized via STAT3 inhibition. In addition, systemic treatment with A13 in the A20-bearing mice for 60 days resulted in a significant improvement of survival rate and marked reduction of liver metastasis. In summary, our data show that the A13 treatment could effectively be applied to acute leukemia via inhibiting STAT3 signaling pathway. PMID- 26815507 TI - The role of oxidative stress on breast cancer development and therapy. AB - Reactive oxygen species (ROS) are produced by both enzymatic and non-enzymatic systems within eukaryotic cells and play important roles in cellular physiology and pathophysiology. Although physiological concentrations are crucial for ensuring cell survival, ROS overproduction is detrimental to cells, and considered key-factors for the development of several diseases, such as neurodegenerative diseases, cardiovascular disorders, and cancer. Cancer cells are usually submitted to higher ROS levels that further stimulate malignant phenotype through stimulus to sustained proliferation, death evasion, angiogenesis, invasiveness, and metastasis. The role of ROS on breast cancer etiology and progression is being progressively elucidated. However, less attention has been given to the development of redox system-targeted strategies for breast cancer therapy. In this review, we address the basic mechanisms of ROS production and scavenging in breast tumor cells, and the emerging possibilities of breast cancer therapies targeting ROS homeostasis. PMID- 26815508 TI - Downregulation of the WT1 gene expression via TMPyP4 stabilization of promoter G quadruplexes in leukemia cells. AB - The WT1 gene is an important oncogene, and its overexpression is considered as an effective target for anticancer therapy. Regulation of its gene transcription is one way for WT1-targeting drug design. Recently, in silico analysis of some oncogene promoters like WT1 showed some guanine-rich regions with the ability to form G-quadruplex structures. Ligands like 5,10,15,20-tetra(N-methyl-4-pyridyl) porphine (TMPyP4) have predominant effect on G-quadruplex stabilization. The aim of this study was to understand the effect of TMPyP4 on WT1 gene transcription via stabilization of promoter G-quadruplexes. We examined the formation of new G quadruplex motifs in WT1 promoter in the presence of TMPyP4. In order to understand the nature of its interaction with WT1 promoter quadruplexes, differential pulse voltammetry (DPV), circular dichroism (CD), polyacrylamide gel electrophoresis, electrophoretic mobility shift assay (EMSA), polymerase chain reaction (PCR) stop assays, and quantitative RT-PCR were performed. According to the results, the WT1 promoter can form stable intramolecular parallel G quadruplexes. In addition, after 48 and 96 h of incubation, 100 MUM TMPyP4 reduced the WT1 transcription to 9 and 0.4 %, respectively, compare to control. We report that ligand-mediated stabilization of G-quadruplexes within the WT1 promoter can silence WT1 expression. This study might offer the basis for the reasonable design and improvement of new porphyrin derivatives as effective anti leukemia agents for cancer therapy. PMID- 26815509 TI - Difficulty, discrimination and cognitive level of Microbiology exam questions of the Faculty of Medicine of Tunisia. AB - Based on difficulty and discrimination indices and cognitive levels of Bloom, we assessed in this study the quality of Microbiology exam questions (main session 2012-2013, Faculty of Medicine of Tunis). METHODS: We analyzed 70 questions: 16 (exam"A") given to 533 students (1st year), 28 and 26 (exams"B1" and "B2") given respectively to 285 and 292 students (3rd year). For every question, we determined difficulty and discrimination indices and the highest cognitive level required to resolve it. We calculated mean difficulty and discrimination indices for each exam and cognitive level, and mean indices of discrimination for every difficulty degree. RESULTS: The 70 questions were of optimum difficulty (0.58), good discrimination (0.31) and explored mainly (58.57%) the lowest cognitive level. For both years, mean indices of difficulty were acceptable, while those of discrimination were good (0.33) and marginal (0.27) for respectively 3rd and 1st year. "A" explored Lower Orders of Cognitive Skills (LOCS), "B2" both Lower and High Orders and "B1" all orders. Mean difficulty indices of every cognitive level were acceptable except for the median one (0.83). Mean discrimination indices were good for all cognitive levels except for LOCS of the 1st year (0.27). Mean indices of discrimination were marginal (0.29) for difficult questions and good for others. Compared to B2, B1 was more attainable and discriminative, free of poor discrimination questions, and explored all cognitive orders. CONCLUSION: Our study remains specific to particular questions and generalizations seem difficult. However, it can serve as a guideline to other similar studies. PMID- 26815510 TI - [A rare cause of epigastric mass: gastro-duodenal bezoar]. PMID- 26815511 TI - [Biliary atresia and polysplenia syndrome]. AB - Polysplenia syndrome is a rare malformation characterized by the association of multiple rates and other congenital anomalies dominated by cardiac, vascular, intestinal and bile malformations. We report the observation of a patient operated in the neonatal period (3 days) for an upper intestinal obstruction with situs inversus. Surgical exploration noted the presence of multiple rates, a preduodenal vein, a biliary atresia and a duodenal atresia. The surgical procedures performed were a latero-lateral duodeno-duodenostomy and hepatoportoenterostomy of KASAI with simple immediate and delayed outcomes. The follow up was of 23 years. We recall the epidemiological characteristics of this malformative association and we discuss the role played by the prognosis of polysplenia syndrome in the evolution of biliary atresia. The diagnosis and treatment of biliary atresia are always urgent to increase the chances of success of the Kasai, and the chances of prolonged survival with native liver. However, almost all long-term survivors (even anicteric) have biliary cirrhosis, which requires lifelong follow up. PMID- 26815512 TI - [Cutaneous metastasis of a ring cell gastric adenocarcinoma]. AB - INTRODUCTION: Cutaneous metastasis of gastric tumors are very rare. Their topography is generally near to the primitive tumor, in the abdominal wall but rarely in cervical region. AIM: the aim of our study was to describe the topography and the clinic-pathological characteristics of cutaneous metastasis of ring cells gastric adenocarcinoma. Observation1: Our first patient is aged of 33 years has epigastralgias and vomiting. Gastric adenocarcinoma with independent cells was diagnosed by gastroscopy and gastric biopsy made for gastric pain and loss of weigh. During hospitalization, he developed 4 cutaneous nodes localized in cervical region. Cutaneous biopsy with histological examination confirmed the metastatic nature of the nodes. Patient was addressed in oncology unit in order to begin palliative systemic chemotherapy. Observation 2: Our second patient is a women aged of 4 3years who had surgical resection for independent cell gastric carcinoma diagnosed by gastroscpy and biopsy for gastric pain and loss of weigh. She had total gastrectomy without any complications and was addressed in oncology unit for adjuvant chemotherapy. After 2 years, she developed peritoneal carcinosis and cutaneous abdominal nodes. Cutaneous metastasis were confirmed by histological examination of cutaneous biopsy and the patient died within one month. CONCLUSION: Cutaneous metastasis of gastric cancer and especially ring cell adenocarcinoma are rare but do occur. They must be early diagnosed because they modify therapeutic options. Their prognosis remains poor. PMID- 26815513 TI - Laparoscopic cholecystectomy decreases extra surgical site morbidity compared with open cholecystectomy: A propensity matched analysis. AB - BACKGROUND: The ideal way to show treatment effectiveness is through randomized controlled trials the 'gold standard' in evidence-based surgery. Indeed, not all surgical studies can be designed as randomized trials, sometimes for ethical and otherwise, for practical reasons. This article aimed to compare laparoscopic cholecystectomy to open cholecystectomy, according to data from an administrative database, managed by a propensity matched analysis. METHODS: Were included all patients with cholelithiasis admitted in Department B between June 1st, 2008 and December 31st, 2009. In this study, the propensity score represented the probability that a patient would be treated by a procedure based on variables that were known or suspected to influence group assignment and was developed using multivariable logistic regression used here to match patients who had laparoscopic cholecystectomy to a control patient who had open cholecystectomy. The main outcome measure was morbidity. This was expressed as the number of patients with 1 or more complications occurring during the hospital stay or within 30 days following discharge. RESULTS: According to intention to treat, 535 patients had a laparoscopic approach (LC group) and 60 patients had a traditional open approach (OC group) regarding associated cardiac disease, previous laparotomy or when choledocholithiasis was suspected, however intra operative cholangiography showed that there was no choledocolithiasis. According to the propensity score, 28 patients in OC were matched with 58 in LC. Comparison between OC and LC before and after propensity matched analysis showed that OC was associated with a higher rate of Extra Surgical Site morbidity (p= 0.010), a longer median duration of intervention, post-operative stay and overall hospital stay (p= 0. 0001). CONCLUSION: LC should be considered as first-line therapy to treat cholelithiasis surgically even if it becomes necessary to convert to OC because of intra operative findings. PMID- 26815514 TI - Appropriateness of indication for upper gastrointestinal endoscopy in a Tunisian endoscopy unit. AB - BACKGROUND: Upper gastrointestinal endoscopy (UGE) is an increasing and reliable procedure. Given the high costs and potential risks, appropriate indication of UGE may be facilitated by referring to qualifying criteria such as those devised by the European Panel (EPAGE). This prospective study evaluates the applicability and efficacy of these criteria in clinical practice. METHODS: Cross sectional study. Consecutive patients were referred to our unit endoscopy for diagnostic upper gastrointestinal endoscopy between January 2011 and June 2011. Demographic data, indication of the procedure, and endoscopic diagnosis were collected. The appropriateness of UGE was assessed based on EPAGE II criteria before the procedure. RESULTS: EPAGE criteria were applicable in 89.1% of cases. They were 78 men (48.1%) and mean age was 49 years [14 - 91]. Indications for UGE were extremely appropriate, appropriate, inappropriate and uncertain in 21.6%, 47.4%%, 8.8% and 22.2% respectively. Among patients with clinically significant lesions detected by UGE, 70.7% had an appropriate indication. Clinically significant lesions were disclosed in 59% of the appropriate group and 54% of the inappropriate group. All cancers were observed in patients with appropriate indications. Patients with appropriate indication were older than patients belonging to the inappropriate group (53.6 years versus 39.9 years, p =0,0001). CONCLUSION: In this present study, EPAGE criteria were applicable in 89.1% and indication was judged appropriate in more than two-third of cases. However, clinical significant lesions were observed in a proportion of patients with inappropriate indication, and in some relevant clinical situations EPAGE criteria were not applicable. Therefore, even if these criteria are helpful for decision making, final decision must however rely upon practitioner. Qualifying criteria for an appropriate selection of endoscopical procedure adapted to our population are advisable. PMID- 26815515 TI - Ataxia-telangiectasia in the south of Tunisia: A study of 11 cases. AB - BACKGROUND: Ataxia-telangiectasia (A-T) is a multisystem disorder characterized by progressive neurologic impairment, variable immunodeficiency, impaired organ maturation, X-ray hypersensitivity, oculocutaneous telangiectasia, and a predisposition to malignancy. AIM: We performed this study in order to describe clinical, immunological and molecular features of patients with AT followed in the south of Tunisia Methods: we performed a retrospective study (1996-2012) in the south of Tunisia about all cases of A-T in order to describe their clinical, immunological and molecular features. RESULTS: 11 cases of AT were found. The mean age at onset of symptoms was 20 months with extremes varying from 3 months to 4 years. The median time to diagnosis was 3.6 years (range: 0-12 years).The main clinical feature of cerebellar syndrome, ataxia, was present at diagnosis in 8 patients and occurred at mean ages of 2.8 years. Ocular telangiectasia occurred at a mean age of 3.9 years (extremes: 3 months and 7 years). Recurrent sino pulmonary infections that affected 7 children occurred at the mean age of 4.3 years. The most common humoral immune abnormality was serum IgA deficiency. Lymphopenia was found in 7 cases and lack of CD4 T in 6 cases. Cytogenetic analyses showed chromosomal instability in all children and a translocation (7 14) in two patients. A molecular diagnosis established in 6 patients from 4 families showed 5 different mutations of ATM gene. After an average decline of 5 years and 6 months, 7 patients died of severe pulmonary infection. Among them, 3 were ATM mutated. CONCLUSION: Morbidity and mortality among patients with A- T are associated with ATM genotype. PMID- 26815516 TI - [Violence against women in the marriage : Cross-sectional study in the family planning clinic Monastir]. AB - BACKGROUND: Violence against women in the marriage is now recognized as a violation of human rights and as a major problem of public health. AIM: The objectives of this study were to estimate the prevalence, specify the typology and to determine associated factors with violence against women in the marriage. METHODS: It was a cross-sectional study carried on 197 married women recruited in family planning center of Monastir, by means of a questionnaire containing some sociodemographic characteristics of the consultant and her spouse and the Woman Abuse Screening Tool to estimate the violence in the marriage Results : The lifetime prevalence of violence against women in the marriage was 56.9%. The most common form of violence was psychological (56.9%), followed by economic violence (41.1%), physical violence (32%) and sexual violence (10.6%). The combination of at least two forms of violence was reported by 84% of victims. The precarious professional status of consultant and her spouse, spouse's alcoholism, the number of children upper for three were the main factors associated with violence in marriage. CONCLUSION: These results justify the implement of screening and support programs for women victims of violence in marriage. PMID- 26815517 TI - Laparoscopic liver resection: initial experience in a North-African single center. AB - BACKGROUND: Over past decades laparoscopic liver resection (LLR) has gained wide acceptance among hepatobiliary surgeons community. To date, few data are available concerning LLR programs in developing countries. This study aimed to assess feasibility and safety of LLR in a Moroccan surgical unit. METHODS: From June 2010 to February 2013, patients that received LLR were identified from a prospective "liver resection" database and included in this study. Parenchymal transection was performed using Harmonic scalpel and bipolar clamp with no Intraoperative ultrasound use or systematic pedicle clamping. LLR difficulty was categorized into 3 categories according to Louisville-statement (I-III). Demographic informations, liver lesion informations, operative details, pathological tumor-margin and 1-months postoperative morbidity according to Clavien-Dindo(C-D) classification were analyzed. RESULTS: Among 104 patients who underwent liver resection 13(12,5%) had LLR. There were 7 females and 6 males with mean age of 57,5 +/- 17 years. LLR was performed for benign lesions in 3 cases and malignant ones in 10 (77%) patients: hepatocarcinoma in 7 patients and synchronous rectal-liver metastasis in 3 patients. Lesions were solitary in 12 (92%) patients with median size of 50mm (15 mm-150 mm). Patients with liver metastasis received combined laparoscopic rectal and liver resection. We used pure laparoscopic approach in 12 (92%) patients and hybrid one in 1 patient. LLR difficulty was category I, II and II in respectively 3(23%), 6(46%) and 4(31%)patients. Conversion rate to open liver resection was 15%. Mean blood loss was 395 min +/- 270 min with no hepatic pedicle clamping or peroperative blood transfusion. All resections were tumor free margin. Mortality rate was nil and morbidity occurred in 4(30%) patients: ascites (C-D 2) and pelvic sepsis in combined resections (CD 3b). Median hospital stay was 6 days. CONCLUSION: Laparoscopic liver resection in our context is safe in selected patients, since no operative mortality, blood transfusion requirement or palliative resection was recorded and liver related morbidity rate was low. Intraoperative ultrasound liver examination capacities are mandatory to improve laparoscopic liver resection program's quality and extend indications. PMID- 26815518 TI - Assessment of MYCN amplification status in Tunisian neuroblastoma: CISH and MLPA combining approach. AB - BACKGROUND: Neuroblastoma (NB) shows a complex combination of genetic aberrations. Some of them represent poor genetic prognosis factors that require specific and intensive chemotherapy. MYCN amplification consists of the major bad outcome prognostic factor, it is indeed frequently observed in aggressive neuroblastomas. To date different methods are used for MYCN status detection. OBJECTIVES: The primary aim of our study was to provide a critical assessment of MYCN status using 2 molecular techniques CISH and MLPA. We also focused on the correlation between neuroblastoma genetic markers and patient's clinical course among 15 Tunisian patients. METHODS: we developed a descriptive study that includes 15 pediatric Tunisian patients referred to our laboratory from 2004 to 2011. We reported the analysis of fresh and FFPE NB tumors tissues. RESULTS: No significant correlation was found between COG grade and patients overall survival. Assessment of NMYC gene copy number by kappa statistic test revealed high concordance between CISH and MLPA tests (kappa coefficient = 0.02). CONCLUSION: Despite misdiagnosing of MYCN status fewer than 5 copies, MLPA remains an effective molecular technique that enables a large panel of genomic aberrations screening. Thus combining CISH and MLPA is an effective molecular approach adopted in our laboratory. Our results allow pediatric oncologists to set up the first Neuroblastoma therapeutic strategy based on molecular markers in Tunisia. PMID- 26815519 TI - [Information needs of Moroccan elderly cancer patients]. AB - BACKGROUND: Announcing cancer to a patient is not a simple task. Usually doctors fail to inform patients about the diagnosis and it is more likely in older people .The need of information in cancerous elderly is not well established. In developed countries, there is evidence that the majority of old patients are demanding exhaustive information about their disease, treatment and prognosis. AIM: In developing countries where social and cultural issues are different, perception of cancer in elderly is not well studied. Therefore we conducted a prospective study on Moroccan elderly cancerous need of information about their disease. METHODS: This is a prospective descriptive study, Conducted in the National Institute of Oncology of Morocco, cancerous patients older than 70 were included. A questionnaire was given to participants. Demographics, disease characteristics, social, economical and cultural features were recorded. RESULTS: One hundred and fifty patients responded to the questionnaire. Mean age was 73. 72.7% of patients were diagnosed in advanced stages. Illiteracy was found in 76%. 87.3% of patients did not have health insurance. All patients were Muslim, practicing in 97%. 57% ignored diagnosis. 80% didn't want to know further information about prognosis and treatment side effects. Family protection from information was found in 70%. CONCLUSION: Moroccan elderly affected with cancer are less demanding of details about their illness.Illiteracy and cultural background may play a major role, Relatives overprotection is also influencing. PMID- 26815520 TI - [Extended pulmonary tuberculosis and immunocompetence: causes and consequences]. AB - BACKGROUND: Despite scientific advances, extended forms of pulmonary tuberculosis are still relevant. The aim of our study was to determine clinical features and outcome of extended pulmonary tuberculosis in immunocompetent patients. METHODS: Retrospective comparative study including 100 patients HIV negative, presenting pulmonary tuberculosis divided into 2 groups of 50 patients (group1: extended tuberculosis and group2: localized tuberculosis). Tuberculosis was considered extended when reaching above one lobe. RESULTS: The average age was comparable in the 2 groups (p = 0.138). In group1, we noted a higher incidence of diabetes (p = 0.037) and malnutrition (p = 0.045). Clinically, patients in group1 had more general signs (p=0.033) and dyspnoea (p=0.037). Biologically, anemia (p<0.001), leukocytosis (p=0.05), elevated CRP (p=0.031), thrombocytosis (p=0.023), hyponatremia (p = 0.001) and liver disturbances (p = 0.001) were significantly more frequent in group1. Concerning the evolution, time to smear negativity was significantly longer (p=0.012). Similarly, radiological sequelae were more frequent (p = 0.02) and more extensive (p = 0.012). Positive predictive value of radiological extent in disease evolution was 62% with a confidence interval between 47.2% and 75%. CONCLUSIONS: The extent of pulmonary tuberculosis is an important factor in clinical and biological presentation and disease evolution. Indeed, patients with extended tuberculosis develop more severe presentation and are more likely to develop parenchymal sequelae. PMID- 26815521 TI - [Indigenous malaria in Tunisia: 4 cases registered in 2013 in Tunisia]. AB - BACKGROUND: Malaria has been eliminated in Tunisia since 1979, but the country remains, like all other countries harboring the vector, exposed to the potential risk of resurgence. OBJECTIVES: Describe the clinical and epidemiological investigation of 4 cases of autochthonous malaria in July 2013 and report the main actions of regional and national response. METHODS: Retrospective descriptive survey of the 4 clinical observations as well as the study of the regional report data of basic health care for the region of Tunis in 2013. RESULTS: Febrile table concomitant for 4 Tunisian male patients, aged from 21 to 27 years old ; fortuitous discovery of Plasmodium falciparum when checking thrombocytopenia of patient 1 ; diagnosis in cascade of other cases following the epidemiological investigation and field consultation with clinicians ; 3 simple forms and a neuromalaria of favorable evolution ; negative entomological survey for anopheles ; elimination of imported malaria and blood-borne ; airport malaria highly probable. The response included the establishment of a regional and national monitoring unit, an information program aimed at health professionals concerned and public opinion, the involvement of health and entomology teams for the detection and census of potential larval habitats and the implementation of local mosquito eradication measures. CONCLUSION: The clinical vigilance and competent biologist's eye is necessary to prevent the resurgence of this disease. The epidemiological surveillance system should be maintained and kept as well as the food safety standards monitoring at the borders. PMID- 26815522 TI - [Epidemiological aspects of malignant melanoma of the uvea in Tunisia]. AB - BACKGROUND: to assess clinical factors that may influence the prognosis of malignant melanoma of the uvea METHODS: We conducted a retrospective study from January 1990 to December 2013, involving 80 patients suffering from malignant melanoma of the uvea. We determined the location, the size, the tumor thickness, the clinicopathological aspect, the degree of pigmentation of the uveal melanoma, and associated signs Results: Factors significantly associated with poor prognosis were: a tumor location (p = 0.01), the infiltrative or fungus aspect (p = 0.001), a diameter equal to or larger than 10 mm (p = 0.003), the thickness greater than or equal to 5 mm (p = 10-3), achromatic or hyperpigmented melanomas (p = 0.02) and retinal detachment (p = 10-3). CONCLUSION: Clinical prognostic factors are important to know because they determine the evolutionary profile and the metastatic potential of the uveal melanoma. PMID- 26815523 TI - Catatonia in adolescents: series of 12 inpatients. AB - BACKGROUND: Catatonia is one of the most severe psychiatric syndromes that might be caused by many medical as well as psychiatric conditions. Catatonia in adolescents is rare and largely understudied. AIMS: This papers aims to examine cases of catatonia among adolescent psychiatric inpatients, and to scrutinize both the etiologies and the management options. METHODS: A retrospective descriptive study involving all cases of catatonia among adolescents admitted to the Department of Child and Adolescent Psychiatry in Razi Hospital - Manouba - Tunisia between January 2006 and December 2013. Catatonia was confirmed by Bush Francis Catatonia Rating Scale. Medical records were examined for gender, age, clinical presentation, medical or psychiatric diagnosis as well as management. Psychiatric diagnoses were made according to the DSM-IV criteria. RESULTS: Our series consisted of 12 cases, aged between 12 and 16 with a sex ratio male/female of 0.5. Catatonia was due to a medical condition in three cases and to a psychiatric disorder in the other nine cases. Psychiatric diagnoses included: manic episode (n=3), major depressive episode (n=2), schizophrenia (n=2), pervasive developmental disorder (n=1) and conversion disorder (n=1). CONCLUSION: Catatonia is rare yet life-threatening. Careful and thorough examination is needed to determine the etiological disorder, on which depend both treatment and prognosis. PMID- 26815524 TI - PSMA-PSA clones controlled by full Akt phosphorylation (T308+,S473+) recapitulate molecular features of human prostate cancer. AB - BACKGROUND: (PSMA+,PSA+) and (PSMA+,PSA-) are the two most individual clones that we have previously identified during prostate cancer (PC) progression. However, molecular signatures associated with these distinct PSMA-PSA prostate clones and their specific correlation with disease outcome is yet to be defined. AIM: Since Akt is a major pathway involved in the critical activating events that leads to malignant form of the disease, we studied the involvement of full Akt activation (T308+,S473+) connected with serum PSA levels, tissue PSMA expression and angiogenic activity on the emergence of (PSMA+,PSA+) and (PSMA+,PSA-) PC clones. METHODS: The study was carried out in 6 normal prostate, 25 benign prostate hyperplasia (BPH) and 23 (PC). Immunohistochemical analysis was performed to study the expression of PSMA, PSA, pAkt(T308), pAkt(S473) and CD34 in prostate tissues. The evaluation of angiogenesis was made by CD34 immune marker. Serum levels of PSA were assayed by Immulite autoanalyser. RESULTS: The most relevant result showed that, among PC patients with pAkt (T308+,S473+) profile, patients that exhibit the (PSMA+,PSA+) clone have .higher serum PSA levels, tissue PSMA expression and angiogenic activity than those with (PSMA+,PSA-) clone. Although have the same (PSMA+,PSA+) prostate clone, BPH patients have distinct molecular biological features compared to PC patients among pAkt (T308+,S473+) profile. In fact, among patients with maximal Akt activation, the (PSMA+,PSA+) PC clone is characterized by higher serum PSA levels, tissue PSMA production and intensive angiogenic activity than (PSMA+,PSA+) BPH clone. CONCLUSION: These findings emphasize the potential role of the full Akt activation (T308+,S473+) in expansion of several PSMA-PSA prostate clones capable of driving both human PC initiation as well as progression to a metastatic phenotype. Pinpoint patients according to PSMA-PSA clones could recapitulate the histological and molecular features of human PC and may offer a novel approach for controlling metastasis. PMID- 26815525 TI - [Development and validation of a new HPLC method for determination of Lamotrigine and clinical application]. AB - BACKGROUND: Lamotrigine is an effective anticonvulsant drug used in the treatment of epilepsy. It has a narrow therapeutic range, a large inter and intra individual pharmacokinetic variability and some concentration-dependent side effects. AIM: The aim of this study was to develop and validate a new method for lamotrigine quantitation in plasma using HPLC with UV/visible detection. METHODS: A rapid HPLC-UV method was developed for the determination of lamotrigine in plasma. All solvents used were HPLC grade. RESULTS: After liquid-liquid extraction, chromatographic separation was achieved using an RP 18 (250 mm) column. The mobile phase was composed of acetonitrile and 0.1 M potassium dihyrogenophosphate (25/75) (v/v). Barbital sodium was used as internal standard. This technique was linear over the 2 MUg/mL to 50 MUg/mL range (r= 0.99). Detection and quantification limits were 0.07 MUg/mL and 0.21 MUg/mL, respectively. Within-day coefficient of variation (13.37 to 16 %) and day-to-day coefficients of variation (15.68 to 16.63 %) at three different concentrations. Under these conditions, each analysis required no longer than 10 min. We finally evaluated the plasma concentrations of lamotrigine in Tunisian patients treated with this drug. CONCLUSION: The results found are similar to those previously described and the developed method is repeatable and reproducible. It can be used for clinical applications. PMID- 26815526 TI - [Cystic fibrosis: A report of 33 pediatric Tunisian cases]. AB - BACKGROUND: The frequency of cystic fibrosis is unknown in Tunisia, regarding the limited number of reported surveys and patients. AIM: to determine the clinical characteristics, outcome and genetic data of cystic fibrosis in Tunisian pediatric patients. METHODS: Cases of cystic fibrosis managed at pediatric departments of Tunis, during 15 years (1997-2012), were reviewed. RESULTS: 33 children (23 males and 10 females) were enrolled. The Onset was within the first year of life in 26 patients. Revealing symptoms were the following: recurrent bronchopneumonia (28 cases), chronic diarrhea (17 cases), hepatomegaly (6 cases), malnutrition (15 cases), pseudo Bartter syndrome (3 cases), edemaanemia- hypoprotidemia (4 cases) and meconium ileus (4 cases). The diagnosis was confirmed by sweat test and genotypic data, the F508 del was the most frequent mutation (17 cases). Several complications had occurred during follow-up: chronic pseudomonas aeruginosa infection (15 cases), chronic respiratory failure (14 cases), recurrent hemoptysis (2 cases), pleural effusion (3 cases) and cirrhosis (2 cases). Ten patients died at a mean age of 7 years. One patient had pulmonary transplantation. Prenatal diagnosis was performed in 9 families. CONCLUSION: In Tunisia, cystic fibrosis is not exceptional, but its diagnosis is delayed. Our survey is characterized by more severe earliest forms, difficult and insufficient therapeutic management. A Better medical awareness and a national action plan are needed. PMID- 26815527 TI - [Radiotherapy in the management of painful bone metastases at The National Institute of Oncology in Morocco: data from one year follow-up of 86 patients]. AB - BACKGROUND: Radiation therapy plays an essential role in the management of pain caused by bone metastases Objectives: Evaluate the effect of radiation for the relief of pain caused by bone metastases. METHODS: We conducted a prospective study of 86 patients suffering from pain associated with bone metastases treated at our department by external radiotherapy between September 2010 and December 2011. Patients recorded pain severity in the numeric rating scale and analgesic requirements before, at the end of irradiation, then weekly for a month, and every month for a year. RESULTS: The median age of patients was 54 years (28-75 years). There were 45 (52.3%) women and 41 (47.7%) men. Radiotherapy was delivered in a multifraction schedule to a total dose of 30 Gy in 72% of patients or in a single fraction of 8 Gy in 28% of patients. A favorable analgesic response was observed in 59 (68.6%) patients with 8 (9.3%) complete responses and 51 (59.3%) partial responses. The median time-to-response was 2 weeks (0-7 weeks), and the median duration of pain relief was 22 weeks (9-46 weeks). CONCLUSION: Radiotherapy is effective in relieving pain associated with bone metastases in the majority of patients. PMID- 26815528 TI - Appendiceal collision tumors. PMID- 26815529 TI - [Calcified cerebral hydatid cyst]. PMID- 26815530 TI - [Macrophage activation syndrome revealing disseminated mycobacterium tuberculosis]. PMID- 26815531 TI - [Diagnosis and practical management of extra-uterine leiomyoma]. PMID- 26815532 TI - Clinical and Molecular Characterization of BSCL2 Mutations in a Taiwanese Cohort with Hereditary Neuropathy. AB - BACKGROUND: A small group of patients with inherited neuropathy that has been shown to be caused by mutations in the BSCL2 gene. However, little information is available about the role of BSCL2 mutations in inherited neuropathies in Taiwan. METHODOLOGY AND PRINCIPAL FINDINGS: Utilizing targeted sequencing, 76 patients with molecularly unassigned Charcot-Marie-Tooth disease type 2 (CMT2) and 8 with distal hereditary motor neuropathy (dHMN), who were selected from 348 unrelated patients with inherited neuropathies, were screened for mutations in the coding regions of BSCL2. Two heterozygous BSCL2 mutations, p.S90L and p.R96H, were identified, of which the p.R96H mutation is novel. The p.S90L was identified in a pedigree with CMT2 while the p.R96H was identified in a patient with apparently sporadic dHMN. In vitro studies demonstrated that the p.R96H mutation results in a remarkably low seipin expression and reduced cell viability. CONCLUSION: BSCL2 mutations account for a small number of patients with inherited neuropathies in Taiwan. The p.R96H mutation is associated with dHMN. This study expands the molecular spectrum of BSCL2 mutations and also emphasizes the pathogenic role of BSCL2 mutations in molecularly unassigned hereditary neuropathies. PMID- 26815534 TI - Erratum to: Analysis of pediatric airway morphology using statistical shape modeling. PMID- 26815533 TI - Diffuse Optical Characterization of the Healthy Human Thyroid Tissue and Two Pathological Case Studies. AB - The in vivo optical and hemodynamic properties of the healthy (n = 22) and pathological (n = 2) human thyroid tissue were measured non-invasively using a custom time-resolved spectroscopy (TRS) and diffuse correlation spectroscopy (DCS) system. Medical ultrasound was used to guide the placement of the hand-held hybrid optical probe. TRS measured the absorption and reduced scattering coefficients (MUa, MUs') at three wavelengths (690, 785 and 830 nm) to derive total hemoglobin concentration (THC) and oxygen saturation (StO2). DCS measured the microvascular blood flow index (BFI). Their dependencies on physiological and clinical parameters and positions along the thyroid were investigated and compared to the surrounding sternocleidomastoid muscle. The THC in the thyroid ranged from 131.9 MUM to 144.8 MUM, showing a 25-44% increase compared to the surrounding sternocleidomastoid muscle tissue. The blood flow was significantly higher in the thyroid (BFIthyroid = 16.0 * 10-9 cm2/s) compared to the muscle (BFImuscle = 7.8 * 10-9 cm2/s), while StO2 showed a small (StO2, muscle = 63.8% to StO2, thyroid = 68.4%), yet significant difference. Two case studies with thyroid nodules underwent the same measurement protocol prior to thyroidectomy. Their THC and BFI reached values around 226.5 MUM and 62.8 * 10-9 cm2/s respectively showing a clear contrast to the nodule-free thyroid tissue as well as the general population. The initial characterization of the healthy and pathologic human thyroid tissue lays the ground work for the future investigation on the use of diffuse optics in thyroid cancer screening. PMID- 26815535 TI - MycN Is Critical for the Maintenance of Human Embryonic Stem Cell-Derived Neural Crest Stem Cells. AB - The biologic studies of human neural crest stem cells (hNCSCs) are extremely challenging due to the limited source of hNCSCs as well as ethical and technical issues surrounding isolation of early human embryonic tissues. On the other hand, vast majority of studies on MycN have been conducted in human tumor cells, thus, the role of MycN in normal human neural crest development is completely unknown. In the present study, we determined the role of MycN in hNCSCs isolated from in vitro-differentiating human embryonic stem cells (hESCs). For the first time, we show that suppression of MycN in hNCSCs inhibits cell growth and cell cycle progression. Knockdown of MycN in hNCSCs increases the expression of Cdkn1a, Cdkn2a and Cdkn2b, which encodes the cyclin-dependent kinases p21CIP1, p16 INK4a and p15INK4b. In addition, MycN is involved in the regulation of human sympathetic neurogenesis, as knockdown of MycN enhances the expression of key transcription factors involved in sympathetic neuron differentiation, including Phox2a, Phox2b, Mash1, Hand2 and Gata3. We propose that unlimited source of hNCSCs provides an invaluable platform for the studies of human neural crest development and diseases. PMID- 26815537 TI - Correction: Effects of Ga-Te interface layer on the potential barrier height of CdTe/GaAs heterointerface. AB - Correction for 'Effects of Ga-Te interface layer on the potential barrier height of CdTe/GaAs heterointerface' by Shouzhi Xi et al., Phys. Chem. Chem. Phys., 2016, 18, 2639-2645. PMID- 26815538 TI - Series on vascular injuries. Part III: complex injuries and difficult problems : Surgical strategies for their management. PMID- 26815536 TI - The wheat homolog of putative nucleotide-binding site-leucine-rich repeat resistance gene TaRGA contributes to resistance against powdery mildew. AB - Powdery mildew, one of the most destructive wheat diseases worldwide, is caused by Blumeria graminis f. sp. tritici (Bgt), a fungal species with a consistently high mutation rate that makes individual resistance (R) genes ineffective. Therefore, effective resistance-related gene cloning is vital for breeding and studying the resistance mechanisms of the disease. In this study, a putative nucleotide-binding site-leucine-rich repeat (NBS-LRR) R gene (TaRGA) was cloned using a homology-based cloning strategy and analyzed for its effect on powdery mildew disease and wheat defense responses. Real-time reverse transcription-PCR (RT-PCR) analyses revealed that a Bgt isolate 15 and salicylic acid stimulation significantly induced TaRGA in the resistant variety. Furthermore, the silencing of TaRGA in powdery mildew-resistant plants increased susceptibility to Bgt15 and prompted conidia propagation at the infection site. However, the expression of TaRGA in leaf segments after single-cell transient expression assay highly increased the defense responses to Bgt15 by enhancing callose deposition and phenolic autofluorogen accumulation at the pathogen invading sites. Meanwhile, the expression of pathogenesis-related genes decreased in the TaRGA-silenced plants and increased in the TaRGA-transient-overexpressing leaf segments. These results implied that the TaRGA gene positively regulates the defense response to powdery mildew disease in wheat. PMID- 26815539 TI - Temporary vascular shunts. AB - Temporary vascular shunts have been used for nearly 100 years in patients. Originally, they were used as vascular grafts that were likely to thrombose as collaterals would hopefully develop. More recently, they have been used as a device to be replaced by a permanent vascular graft during the same operation or at a reoperation. Indications for the use of shunts are a "damage control" procedure for a peripheral or truncal vascular injury, Gustilo IIIC fracture of an extremity, need for perfusion as a complex revascularization is performed, and planned replantation of a hand, forearm, or arm. They are used in approximately 8% of vascular injuries treated in urban trauma centers in the United States and have an excellent patency rate without heparinization. PMID- 26815540 TI - Extremity compartment syndrome and fasciotomy: a literature review. AB - Trauma surgeons frequently encounter injured limbs at risk for compartment syndrome. This article reviews data regarding the pathophysiology of compartment syndrome, factors in measuring compartment pressures, thresholds for performing fasciotomies, and outcomes from the development of compartment syndromes and performing fasciotomies. PMID- 26815543 TI - Increased mortality with undertriaged patients in a mature trauma center with an aggressive trauma team activation system. AB - PURPOSE: The American College of Surgeons Committee on Trauma (ACS-COT) has determined that a 5 % pre-hospital undertriage [UT; defined as Injury Severity Score (ISS) > 15 and not sent to a trauma center] is an acceptable rate for pre hospital transfer to a non-trauma center. We sought to determine if this level of undertriage is acceptable within a mature Level II trauma center as a measure of the adequacy of its trauma activation system. METHODS: Our trauma activation system encompasses anatomic, physiologic, and mechanism of injury criteria. We defined UT as ISS > 15 and no trauma activation. All UT patients during the period 2000-2010 were compared to properly triaged patients (CT). The variables examined were mortality, emergency department (ED) length of stay (LOS), hospital LOS, complications, Coumadin use, and age >64 years. RESULTS: There were 18,324 patients admitted, with 1,156 (6.3 %) UT. UT is associated with an increase in mortality [odds ratio (OR) 3.0; 95 % confidence interval (CI) 2.4-3.8; p < 0.001), longer ED LOS (OR 54.5; 95 % CI 45.5-63.5; p < 0.001), and longer hospital LOS (OR 1.7; 95 % CI 1.4-2.1; p < 0.001). In addition, UT patients had a two-fold increase in complications (OR 2.0; 95 % CI 1.6-2.5; p < 0.001). When controlling for age >=65 years, Revised Trauma Score (RTS) > 7.0, and one or more co-morbidities, UT patients had 2.18 times higher odds of mortality than their CT counterparts (OR 2.18; 95 % CI 1.57-3.01; p < 0.001). Patients on pre-hospital Coumadin (OR 3.61; 95 % CI 3.04-4.30; p < 0.001) and age >64 years (OR 4.93; 95 % CI 4.36-5.58; p < 0.001) were significant predictors of being undertriaged. A p value <= 0.05 was considered to be significant. CONCLUSIONS: Standard trauma activation criteria may not be adequate to identify the at-risk severely injured trauma patient. Further refinement of in-house trauma triage protocols is necessary if trauma centers are to improve outcomes following trauma. PMID- 26815542 TI - Deep venous thrombosis following different isolated lower extremity fractures: what is known about prevalences, locations, risk factors and prophylaxis? AB - INTRODUCTION: Deep venous thrombosis (DVT) offers a high risk of morbidity and mortality, especially in case of pulmonary embolism. Precise data as to DVT after isolated lower extremity fractures (ILEFs) are rare. Even organizations like the American Academy of Orthopaedic Surgeons or the American College of Chest Physicians do not state exact recommendations as to optimal DVT prophylaxis (ppx) after ILEFs. PREVALENCE: The incidence of DVT ranges from 5 to 86 % depending on the fracture whereas femur fractures offer the highest risk for clotting. The incidence seems to decrease in more distal fractures. LOCATION: The risk to develop proximal clots is likely low, however, especially these are feared by surgeons. DVT can occur in both the injured and uninjured leg with a trend for higher incidences in the injured leg. RISK FACTORS: Risk factors for DVT after ILEF seem to be similar to risk factors for DVT development after orthopaedic surgery and in general. Risk factors caused by surgeons are the use of a tourniquet, prolonged operative time and a delay from injury to surgery. PROPHYLAXIS: Low molecular weight heparin is favoured by many authors, however, warfarin and acetylsalicylic acid are also used. Clear recommendations are still missing. CONCLUSION: The rate of morbidity caused by DVT after ILEF is poorly understood so far. Exact data on prevalences are missing and optimal DVT prophylaxis still has to be defined. PMID- 26815541 TI - Vascular complications and special problems in vascular trauma. AB - The evaluation and management of patients with vascular trauma or injury often involve rapid decision making in less than ideal circumstances. Immediate consequences such as hemorrhage, ischemia, compartment syndrome, thrombosis, and embolization may be life threatening and require immediate intervention. In addition, a number of regional and systemic complications of the initial vascular pathology are possible, such as shock, acute renal failure, myocardial infarction, or stroke. Understanding the disease process, as well as the optimal diagnostic and therapeutic interventions, is critically important to minimize the risk of these highly morbid or potentially mortal complications. The managing physician must be adept and well versed at both the initial management of the specific vascular injury and the many potential complications that may subsequently arise. This article will review a number of vascular-specific complications and provide details of strategies for their prevention or optimal management. These problems include traumatic injuries to the arterial or venous system, failure of vascular repairs or reconstructions, surgical site and graft infections, anastomotic complications, and compartment syndromes. In addition, arterial and venous complications secondary to the use of illicit intravenous drug use and cocaine-related vascular injury will be discussed. Finally, the increasingly important topic of iatrogenic or procedure-related vascular injuries and complications will be reviewed. PMID- 26815544 TI - Clinical outcomes of multiple rib fractures: does age matter? AB - PURPOSE: To evaluate the clinical outcomes of multiple rib fracture due to blunt trauma in young patients, a 3-year retrospective study was conducted. Patients with >=3 rib fractures were divided into two groups (group I: <45 years old and group II: >=45 years old). Mortality, hospital stay, ventilatory support, chest tubes insertion and associated injuries were studied. RESULTS: Of the 902 patients admitted with blunt chest trauma, 240 (27 %) met the inclusion criteria and 72.5 % patients were <45 years old. The most common causes of injury were motor vehicle crash (59 %) and fall (29 %). The Injury Severity Score (ISS) was higher in group I (16 +/- 9 vs. 13 +/- 6; p = 0.04). Hospital mortality was higher in group II (6 vs. 2 %; p = 0.18). Pneumothorax, haemothorax and ventilatory support were comparable. Patients in group II were more likely to undergo chest tubes insertion (26 vs. 14 %; p = 0.04), while group I had a significantly higher incidence of associated abdominal injuries (25 vs. 12 %; p = 0.03). CONCLUSION: Old age presenting with rib fractures is associated with higher mortality in comparison to young age; however, this difference becomes statistically insignificant in the presence of multiple rib fracture. PMID- 26815545 TI - Are soft tissue measurements on lateral cervical spine X-rays reliable in the assessment of traumatic injuries? AB - INTRODUCTION: Traumatic neck pain is a common presentation to the emergency department. Lateral plain radiographs remain the primary investigation in the assessment of these injuries. Soft tissue assessment forms an integral component of these radiographs. They can provide information on subtle injuries that may not be obvious. Many methods are used to assess the prevertebral soft tissue shadows. The two more commonly used techniques include the 'seven at two and two at seven' rule (method 1) and the ratio of the soft tissues with respect to the vertebral width (method 2). AIM: To assess which of the above two methods in assessing cervical spine soft tissue shadows on lateral radiographs is more sensitive in the presence of cervical spine injuries. METHODS: A retrospective analysis of consecutive traumatic cervical spine films performed within a busy trauma tertiary centre over a period of 7 months. Patients were divided into two groups: group 1-fractures; group 2-no fractures. The prevertebral soft tissue shadows were measured at referenced points on the lateral cervical spine films with respect to the above two methods and comparisons between the groups were made. RESULTS: Thirty-nine patients in group 1 were compared to a control group of 60 patients in group 2. Both methods failed to identify any significant differences between the two groups. The sensitivity and specificity for method 1 was 7.6 and 93 %, and for method 2, they were 7.6 and 98 %, respectively. CONCLUSION: There is no significant difference between the soft tissue shadows when comparing patients with and without cervical spine fractures on lateral radiographs. Both commonly used measures of soft tissue shadows in clinical practice are insensitive in identifying patients with significant osseous injuries. They, therefore, do not offer any further value in interpreting traumatic cervical spine radiographs. The management of patients with cervical spine trauma in the absence of obvious osseous injury on standard radiographs should warrant a computed tomography (CT) scan if clinically indicated. PMID- 26815546 TI - Evaluation of the use of the hook plate in Neer type 2 lateral clavicle fractures and Rockwood types 3-5 acromioclavicular joint dislocations. AB - PURPOSE: For most types of acromioclavicular (AC) injuries, treatment is well established. For Neer type 2 lateral clavicle fractures and Rockwood types 3-5 AC dislocations, the ideal treatment is still a point of debate. The purpose of this study was to evaluate the functional and radiological outcome in patients treated for one of these two lesions in our hospital. METHODS: Our study group consisted of 30 patients with a Neer type 2 lateral clavicle fracture (n = 19) or Rockwood types 3-5 AC dislocation (n = 11) treated with the clavicle hook plate. All implants were removed after healing. At a mean follow-up of 40 months (12-92), data were collected by the analysis of questionnaires (DASH, NSST, OSS, SF-36), clinical examination (Constant-Murley score), and radiological evaluation (Zanca view). RESULTS: The mean Constant score was 88 [standard deviation (SD) 8] compared to 92 (SD 6) on the contralateral non-operated side. The questionnaires resulted in the following scores: median DASH: 4.5 (0-70); median NSST: 100 (8 100); mean OSS: 41 (SD 8); mean SF-36: 81 (SD 12). The mean coracoclavicular (CC) and AC distances were not significantly different. CONCLUSIONS: This study suggests that hook plate fixation is a reliable treatment for Neer type 2 lateral clavicle fractures and Rockwood types 3-5 AC injuries. It results in a good and comparable function of the shoulder when compared to the contralateral side, high union rate, good to excellent objective and subjective results, and allows early active motion with limited abduction. A disadvantage is the necessity to remove the plate. PMID- 26815548 TI - Computerized dynamic posturography analysis of balance in individuals with a shoulder stabilization sling. AB - INTRODUCTION: Sling immobilization of the upper limb may affect balance. Computerized dynamic posturography (CDP) provides a validated, objective assessment of balance control and postural stability under dynamic test conditions. We tested the balance of individuals with a shoulder stabilization sling (SSS) using an EquiTest machine to objectively assess imbalance while wearing a sling. METHODS: Forty-two right hand dominant (RHD) adults (16 females, 26 males; average age 22 years; range 20-35 years) were included in the study, comprising six controls and two SSS groups with 18 dominant hands (DH) and 18 non dominant hands (NDH). CDP assessed balance by the Sensory Organization Test (SOT), Motor Control Test (MCT), and Adaptation Test (ADT). RESULTS: The composite equilibrium scores (CES) were as follows: controls 80.8 %, sling DH 71.1 versus sling NDH 69.6 %. Sling use has lower CES compared to controls (p = 0.025). The use of a sling caused 31 % of subjects to have decreased CES. 22.9 % of sling users had imbalances. Among sling users, the DH group had 19.1 % imbalances compared to 26.8 % for the NDH group (p = 0.044). There were six absolute falls in the DH group versus 12 in the NDH group. CONCLUSIONS: Wearing a sling causes balance decompensation in almost one-third of healthy volunteers, and this is greater when worn in the non dominant hand, with double the number of falls. This has significant implications for patients having prolonged use of a sling. Consideration should be given to operative procedures or conservative management of shoulder pathology where sling use is required and promotion of the early discontinuation of sling use can be considered. PMID- 26815547 TI - The impact of anemia in moderate to severe traumatic brain injury. AB - PURPOSE: The impact of anemia and restrictive transfusion strategies in traumatic brain injury (TBI) is unclear. The purpose of this study was to examine the outcome of varying degrees of anemia in patients who have sustained a TBI. METHODS: We performed a retrospective study of all adult patients with isolated blunt TBI admitted between January 2003 and June 2010. The impact of increasing severity of anemia (Hb <=8, <=9, or <=10 g/dl measured on three consecutive draws within the first 7 days of admission) and transfusions on complications, length of stay, and mortality was examined using univariate and multivariate analysis. RESULTS: Of the 31,648 patients with blunt trauma admitted to the trauma service during the study period, 812 had an isolated TBI, among which 196 (24.1 %) met at least one of the anemia thresholds within the first 7 days [78 % male, mean age 47 +/- 23 years, Injury Severity Score 16 +/- 8, and head Abbreviated Injury Scale 3.3 +/- 1.0]. Using a logistic regression model, anemia even as low as 8 g/dl was not associated with an increase in mortality [AOR8 = 0.8 (0.2, 3.2), p = 0.771; AOR9 = 0.8 (0.4, 1.6), p = 0.531; AOR10 = 0.6 (0.3, 1.3), p = 0.233] or complications. However, for all patients, the transfusion of packed red blood cells was associated with a significant increase in septic complications [AOR = 3.2 (1.5, 13.7), p = 0.030]. CONCLUSION: The presence of anemia in patients with TBI as low as 8 g/dl was not associated with increased mortality or complications, while the transfusion of red blood cells was associated with a significant increase in septic complications. Prospective evaluation of an optimal transfusion trigger in head-injured patients is warranted. PMID- 26815549 TI - Is computed tomography necessary to determine liver injury in pediatric trauma patients with negative ultrasonography? AB - PURPOSE: Abdominal trauma is the third most common cause of all trauma-related deaths in children. Liver injury is the second most common, but the most fatal injury associated with abdomen trauma. Because the liver enzymes have high sensitivity and specificity, the use of tomography has been discussed for accurate diagnosis of liver injury. METHODS: Our study was based on retrospective analyses of hemodynamically stabil patients under the age of 18 who were admitted to the emergency department with blunt abdominal trauma. RESULTS: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were significantly higher as a result of liver injury. In the patients whose AST and ALT levels were lower than 40 IU/L, no liver injury was observed in the contrast enhanced computed tomography (CT). No liver injury was detected in the patients with AST levels lower than 100 IU/L. Liver injury was detected with contrast enhanced CT in only one patient whose ALT level was lower than 100 IU/L, but ultrasonography initially detected liver injury in this patient. CONCLUSIONS: According to our findings, abdominal CT may not be necessary to detect liver injury if the patient has ALT and AST levels below 100 IU/L with a negative abdominal USG at admission and during follow-up. PMID- 26815550 TI - Special considerations in the interpretation of plain radiographs of the cervical spine in children. A review of the literature. AB - INTRODUCTION: This review provides an overview of the special considerations with regard to correct diagnosis of plain radiographs of the pediatric cervical spine. Injuries to the cervical spine are rare in children. The leading trauma mechanism is motor vehicle injury. Plain radiographs are a common tool in the search for a diagnosis. Taking the growth process into account there are many differences to be found compared to the adult c-spine. Knowledge of these differences is important when working towards the correct interpretation of plain radiographs of the pediatric c-spine. METHODS: To create this review, a literature search of the electronic databases Cochrane, PubMed/MEDLINE and Embase was conducted. RESULTS: Special considerations of plain radiographs of the pediatric c-spine are presented. Biomechanical and embryology specifics have been a focus of this review. They are explained relating on the development of the c-spine. The known auxiliary lines used in the interpreting of the pediatric c-spine are reported. A selection of these auxiliary lines is shown. CONCLUSION: Knowledge of the c spines characteristics is of major importance for every physician involved in pediatric trauma care. This could lead to not only avoiding misdiagnosis but could also lead to avoiding the overuse of computed tomography of the pediatric c spine. PMID- 26815552 TI - ESTES News. PMID- 26815551 TI - Diagnosis of cervical spine injuries in children: a systematic review. AB - OBJECTIVE: The objective of this systematic review was to discuss current knowledge of the diagnostic management of cervical spine (c-spine) injuries in children. METHODS: Studies dealing with this topic were collected from the following sources: MEDLINE via PubMed, Embase, and Cochrane. Where possible, a meta-analysis was performed. Furthermore, the level of evidence for all the included publications was assigned. RESULTS: The incidence of cervical spine injury (CSI) in children is rare (1.39 %). It seems that the upper c-spine is more often injured in children younger than 8 years of age. When a CSI is expected, immobilization should be performed. The best immobilization is achieved with a combination of a half-spine board, rigid collar, and tape. The literature for thoracic elevation or an occipital recess in children younger than 8 years of age is inhomogeneous. The c-spine in children can be cleared by a combination of the National Emergency X-Radiography Utilization Study (NEXUS) low-risk criteria and the Canadian C-Spine Rule. Caution is advised for nonverbal and/or unconscious children. In these children, plain radiographs should be performed. If these images are inadequate or show hints for bony injuries, a computed tomography (CT) of the c-spine should be considered. Additional views of the c spine offer only little information for clearing the c-spine. PMID- 26815553 TI - Offshore Evidence for an Undocumented Tsunami Event in the 'Low Risk' Gulf of Aqaba-Eilat, Northern Red Sea. AB - Although the Gulf of Aqaba-Eilat is located in the tectonically active northern Red Sea, it has been described as low-risk with regard to tsunami activity because there are no modern records of damaging tsunami events and only one tsunami (1068 AD) referred to in historical records. However, this assessment may be poorly informed given that the area was formed by and is located along the seismically active Dead Sea Fault, its population is known to fluctuate in size and literacy in part due to its harsh hyper-arid climate, and there is a dearth of field studies addressing the presence or absence of tsunamigenic deposits. Here we show evidence from two offshore cores for a major paleotsunami that occurred ~2300 years ago with a sedimentological footprint that far exceeds the scarce markers of the historically mentioned 1068 AD event. The interpretation is based on the presence of a laterally continuous and synchronous, anomalous sedimentological deposit that includes allochtonous inclusions and unique structural characteristics. Based on sedimentological parameters, these deposits could not be accounted for by other transport events, or other known background sedimentological processes. PMID- 26815555 TI - Correction: Neurally Encoding Time for Olfactory Navigation. AB - [This corrects the article DOI: 10.1371/journal.pcbi.1004682.]. PMID- 26815554 TI - Lipidomic platform for structural identification of skin ceramides with alpha hydroxyacyl chains. AB - Skin ceramides are sphingolipids consisting of sphingoid bases, which are linked to fatty acids via an amide bond. Typical fatty acid acyl chains are composed of alpha-hydroxy fatty acid (A), esterified omega-hydroxy fatty acid (EO), non hydroxy fatty acid (N), and omega-hydroxy fatty acid (O). We recently established a lipidomic platform to identify skin ceramides with non-hydroxyacyl chains using tandem mass spectrometry. We expanded our study to establish a lipidomic platform to identify skin ceramides with alpha-hydroxyacyl chains. Tandem mass spectrometry analysis of A-type ceramides using chip-based direct infusion nanoelectrospray-mass spectrometry showed the characteristic fragmentation pattern of both acyl and sphingoid units, which can be applied for structural identification of ceramides. Based on the tandem mass spectrometry fragmentation patterns of A-type ceramides, comprehensive fragmentation schemes were proposed. Our results may be useful for identifying A-type ceramides in the stratum corneum of human skin. PMID- 26815556 TI - Enhanced dewatering of waste-activated sludge by composite hydrolysis enzymes. AB - The feasibility of composite hydrolysis enzymes in enhanced dewatering of waste activated sludge (WAS) was verified in this study. A Pearson correlation analysis was conducted to explore the roles of different extracellular polymeric substance (EPS) fractions on WAS dewaterability. The results indicated that tightly bound EPS (TB-EPS) was released into the liquid phase consistently during enzymatic hydrolysis to form soluble EPS (S-EPS) and loosely bound EPS and that the TB-EPS content was positively correlated with the capillary suction time of WAS. A kinetic analysis was carried out to gain further insights into the kinetic variation in TB-EPS removal. It was found that TB-EPS reduction fit a first-order kinetic model and that mild temperature (25-30 degrees C) and a slightly acidic condition were favorable for the improvement of enzyme activity. Solid phase extraction combined with UV-Vis spectroscopy analysis was used to characterize the processes of migration and transformation of the hydrophobic (HPO), transphilic and hydrophilic (HPI) fractions in EPS during the enzymatic process. The results revealed that HPO and HPI were mainly composed of PN and PS, respectively, and that the enzymatic hydrolysis could enhance the transformation of HPI from TB-EPS to S-EPS, which was the dominant mechanism of improving WAS dewaterability. PMID- 26815557 TI - Soil salinity detection from satellite image analysis: an integrated approach of salinity indices and field data. AB - This paper attempts to detect soil salinity from satellite image analysis using remote sensing and geographic information system. Salinity intrusion is a common problem for the coastal regions of the world. Traditional salinity detection techniques by field survey and sampling are time-consuming and expensive. Remote sensing and geographic information system offer economic and efficient salinity detection, monitoring, and mapping. To predict soil salinity, an integrated approach of salinity indices and field data was used to develop a multiple regression equation. The correlations between different indices and field data of soil salinity were calculated to find out the highly correlated indices. The best regression model was selected considering the high R (2) value, low P value, and low Akaike's Information Criterion. About 20% variation was observed between the field data and predicted EC from the satellite image analysis. The precision of this salinity detection technique depends on the accuracy and uniform distribution of field data. PMID- 26815558 TI - A robust X-ray fluorescence technique for multielemental analysis of solid samples. AB - X-ray fluorescence (XRF) quantitation software programs are widely used for analyzing environmental samples due to their versatility but at the expense of accuracy. In this work, we propose an accurate, robust, and versatile technique for multielemental X-ray fluorescence analytical applications, by spiking solid matrices with standard solutions. National Institute of Standards and Technology (NIST)-certified soil standards were spiked with standard solutions, mixed well, desiccated, and analyzed by an energy dispersive XRF. Homogenous targets were produced and low error calibration curves, for the added and not added, neighboring, elements, were obtained. With the addition of few elements, the technique provides reliable multielemental analysis, even for concentrations of the order of milligram per kilogram (ppm). When results were compared to the ones obtained from XRF commercial quantitation software programs, which are widely used in environmental monitoring and assessment applications, they were found to fit certified values better. Moreover, in all examined cases, results were reliable. Hence, this technique can also be used to overcome difficulties associated with interlaboratory consistency and for cross-validating results. The technique was applied to samples with an environmental interest, collected from a ship/boat repainting area. Increased copper, zinc, and lead loads were observed (284, 270, and 688 mg/kg maximum concentrations in soil, respectively), due to vessels being paint stripped and repainted. PMID- 26815560 TI - Minimally Invasive Surgery in Trauma and Emergencies. PMID- 26815559 TI - Impending rupture of saphenous vein graft aneurysm with floating fractured bare metal stent treated by coil embolization and covered stent implantation. AB - Aneurysmal degeneration of a saphenous vein graft (SVG) is a rare, but potentially fatal complication of coronary artery bypass graft (CABG) surgery. In this case report, a patient that had undergone prior CABG surgery and bare metal stent (BMS) implantation at the site of a stenotic SVG lesion presented at our hospital with chest pain, and an SVG aneurysm was detected at the previous BMS implantation site. In addition, the implanted BMS was fractured and floating in the SVG aneurysm. The SVG aneurysm was successfully occluded by percutaneous intervention, using a combination of distal covered stent deployment at the site of the anastomosis between the native coronary artery and the SVG and proximal coil embolization of the aneurysm. PMID- 26815561 TI - Ergonomics and Technical Aspects of Minimal Access Surgery in Acute Surgery. AB - BACKGROUND: Following the general trend in the evolution of minimal access surgery (MAS), the place of laparoscopy for diagnostic and therapeutic procedures in the emergency setting is well defined. As for all laparoscopic procedures, the ergonomic and technical aspects of MAS in acute surgery are important issues. METHODS: Review of the literature. RESULTS: The ergonomic and technical aspects of emergency laparoscopy include the surgeon's and the patient's position; the operating room setup, including the table, the monitor, and the specific equipment; patient preparation adapted as required to potential changes necessary as adapted to the pathology and conversion; the trocar setup, also adapted to the organ and pathology. Specific needs and variations can be necessary, dependent on the patient status, body build, and the pathology being treated. The operating room used for acute surgery should be adapted to evolving laparoscopic techniques, as well as new intraoperative diagnostic and therapeutic modalities. CONCLUSION: High-tech equipment and associated procedures have modified the needs for a modern operating room setup. Laparoscopic procedures for emergency surgery must make use of well-known ergonomic principles and be adapted to the patient and the pathology. PMID- 26815563 TI - Thoracoscopy for Trauma. AB - Thoracoscopy has numerous applications for both diagnosis and treatment in thoracic trauma. It is excellent for the diagnosis of diaphragmatic injuries, mediastinal evaluation, and the assessment of persistent air-leak. It offers therapeutic intervention for diaphragmatic lacerations, thoracic bleeding in stable patients, evacuation of residual hemothorax, air-leaks, and the prevention and treatment of empyema. Judiciously applied, it is a powerful tool in the armamentarium of the trauma surgeon. PMID- 26815562 TI - Laparoscopy in Non-Trauma Abdominal Emergencies. AB - The role for laparoscopy has evolved throughout the years and more evidence has become available to support its use in abdominal emergencies. Although the literature has expanded and more randomized controlled trials are available, skepticism persists concerning the use of laparoscopy in emergency situations. We attempt to provide the readers with a concise review and highlight the most relevant issues and available evidence in seven different non-trauma abdominal emergencies. PMID- 26815564 TI - Laparoscopy in Abdominal Trauma. AB - BACKGROUND: The decision in favor of surgery or nonoperative conservative treatment in blunt and penetrating abdominal trauma requires a precise diagnosis that is not always possible with imaging techniques, whereby there is great danger that an injury to the diaphragm or intestines may be overlooked. To avoid such oversights, indications for exploratory laparotomy have traditionally been generous, to the extent that up to 41% of exploratory laparotomies turn out to be nontherapeutic and could be, or could have been, avoided with laparoscopy. MATERIALS AND METHODS: A diagnostic laparoscopy with therapeutic option should only be attempted in stable patients. Three trocars are usually used and the abdomen is explored systematically, beginning with the right upper quadrant and continuing clockwise. Hollow viscus injuries and injuries to the diaphragm and mesentery can be detected and sutured laparoscopically. Injuries to parenchymal organs are not a primary focus of laparoscopy, but with a laparoscopic approach, they usually no longer bleed in stable patients and can be sealed with tissue adhesive and collagen tamponade to prevent re-bleeding. RESULTS: The routine use of laparoscopy can achieve a sensitivity of 90-100% in abdominal trauma. This can reduce the number of unnecessary laparotomies and the related morbidity. CONCLUSION: Laparoscopy can be performed safely and effectively in stable patients with abdominal trauma. The most important advantages are reduction of the nontherapeutic laparotomy rate, morbidity, shortening of hospitalization, and cost-effectiveness. In the future, new developments in and the miniaturization of equipment can be expected to increase the use of minimally invasive techniques in abdominal trauma cases. PMID- 26815565 TI - Nutrition in Trauma and Critically Ill Patients. AB - Despite significant improvements in the practice of metabolic support of critically ill patients in recent years, malnutrition continues to be common among surgical patients, adding significantly to complications, infections, length of stay, costs, and increased mortality. Furthermore, hypercatabolism is the major metabolic response after major trauma and emergency surgery, making this patient population a unique subgroup of critically ill patients vulnerable to further decline in nutritional status. Many questions have already been answered, such as whether critically ill patients should be fed, when they should be fed, and how nutrients should be delivered. What is not entirely clear is what we should feed critically ill patients at different phases of specific diseases and disorders, as well as whether or not we should enhance and/or modulate patients' immunity. PMID- 26815566 TI - The Influence of Bone Cement Implantation in Primary Hip Arthroplasty on S100B Protein Serum Concentration and Patients' Cognitive Functions as Markers of Brain Damage. AB - OBJECTIVE: The objective of the study was to evaluate the influence of the bone cement used during primary hip arthroplasty on brain functions assessed at the biochemical and clinical levels. The S100B protein is a biochemical marker of brain damage. Its plasma concentration was compared with the results of neuropsychological tests, conducted during the perioperative period. PATIENTS AND METHODS: Two groups of patients who underwent primary hip arthroplasty were analyzed; group one (n = 30) with the use of bone cement (cemented), group two (n = 30) without (cementless). All of the procedures were under spinal anesthesia with intravenous sedation. In each group, S100B protein concentration was examined before the surgery and just after the operation, and 6, 24, and 72 h after the procedure. Two neuropsychological tests were conducted before the surgery and 24 and 72 h after. The patients with preexisting blood flow disturbances inside the carotid and vertebral arteries and those with intraoperative mean arterial pressure below 50 mmHg were excluded from the study. STATISTICAL ANALYSIS: Data were analyzed using SPSS 15.0 for Windows (SPSS Inc., Chicago, IL, USA). The two groups were compared using the Mann-Whitney U-test. The comparison between the groups was done with Wilcoxon's signed ranks test. The correlations were analyzed using Spearman's rho test. RESULTS: There were no significant differences between the two groups in S100B protein concentration before the surgery. Just after the operation, the S100B protein concentration was elevated in both groups, but its level in the cemented group was significantly higher, particularly just after the surgery, and its normalization was slower than in the cementless group. The comparison of time points within each group revealed that there were no significant differences in patients' reaction time in the simple reaction test before and after the surgery (p = 0.056 and 0.163 in the cementless and 0.581 and 0.139 in the cemented groups), but a significantly longer mean reaction time in the choice reaction test was observed within each group after the surgery (p = 0.003 and 0.001 in the cementless and 0.001 and 0.014 in the cemented groups). There were no correlations between S100B protein plasma concentration and the results of the neuropsychological tests. CONCLUSIONS: There was a relationship between bone cement implantation during primary hip arthroplasty and elevated S100B protein plasma concentration during the short postoperative period, but the results of the neuropsychological tests did not reflect this. PMID- 26815567 TI - A Reliable Screening Test to Predict Liver Injury in Pediatric Blunt Torso Trauma. AB - OBJECTIVES: We determined the validity of serumaspartate aminotransferase (AST) and alanine aminotransferase(ALT) as screening tests in the identificationof liver injuries in pediatric torso trauma patients. METHODS: We conducted a retrospective study inpediatric patients < 17 years of age who sustainedblunt trauma and were admitted to an urban traumacenter during a 39-month period. The serum AST andALT levels, injury severity scores (ISS), lengths of hospitaland intensive care unit stays, laparotomy andvascular embolization requirement, mortality rate, andconcomitant injuries were compared betweenpatients with and without liver injury. RESULTS: Of the 40 patients reviewed, 16 patients hadliver injuries. The mean serum AST and ALT levels weremarkedly higher in the liver injury (LI) group than inthe non-liver injury (NLI) group (773.4 IU/l +/- 781.3 [SD]and 613.6 IU/l +/- 640.0 [SD], respectively, and (67.2IU/l +/- 63.2 [SD] and 55.5 IU/l +/- 62.6 [SD], respectively;p < 0.01). One of the 16 LI patients and 20 of the 24 NLIpatients had AST levels < 200 IU/l or ALT levels < 125IU/l. The sensitivity, specificity, and positive and negativepredictive values were 94, 83, 79, and 95%,respectively. CONCLUSIONS: A serum AST > 200 IU/l or an ALT> 125 IU/l are strong predictors of liver injury in childrensustaining blunt torso trauma. We recommend theroutine use of serum transaminase levels as screeningtests in hemodynamically stable patients. PMID- 26815568 TI - Trauma in a Teaching Hospital Outpost: Comprehensive Health Centre, Okoyong, Cross River State, Nigeria. AB - BACKGROUND: Road traffic injuries and other forms of trauma have become a major health problem worldwide, but Africa is the worst hit. This study was designed to evaluate the characteristics of trauma injuries in order to offer solutions for planning in terms of policy formulation and implementation. PATIENTS AND METHODS: The Comprehensive Health Centre, Okoyong, is a rural outpost of the University of Calabar Teaching Hospital. Calabar is located about 45 km away in a rural community close to the highway. Trauma patients seen from January 2004 to December 2004 were studied. RESULTS: In total, 76 trauma patients were recorded. The ages ranged from 2 to 50 years (mean 26.1 years) with a male to female ratio of 3:1. Trauma was mainly due to road traffic injuries, 54 patients (71.1%) (motor vehicle - commercial in 28 patients and motorcycle in 26), followed by assault in 15 patients (19.7%). Laceration and abrasion accounted for 87.8% of injuries. The head and neck was the most common anatomical site injured in 49 patients (47%), followed by the lower limbs in 27 patients (26.0%). The injuries involved 39 passengers/pedestrians (72.3%), while a driver/14 cyclists (27.7%) ranked second. Mortality was 2.6%. CONCLUSION: Trauma was mainly due to road traffic injuries. The development of rural trauma systems and improvements in road and traffic infrastructure would reduce injury, morbidity, and mortality. PMID- 26815569 TI - Polyaxial Locked Implants in the Treatment of Type Vancouver B1 Periprosthetic Fractures of the Femur: Retrospective Clinical Examination in 58 Cases with Review of the Literature. AB - We concluded a retrospective study of the outcomes of a consecutive series of Vancouver B1 and C femoral injuries using two specific locked implants. The study center is a dedicated trauma hospital with a large catchment area. Over a five year period we treated 58 patients with a periprosthetic fracture of the femur with an angular stable plate, defined as the index procedure. The mean age at the index procedure was 72.4 years; 40 patients were female (69%). In 32 cases (55.2%) we saw a hip endoprosthesis, in 21 cases (36.2%) a knee endoprosthesis, and in five cases both (8.6%). Outcome measures were intra- and postoperative complications, bony union, degree of mobility and social status with comparison to the preoperative status, Barthel index, and timed ''up and go'' test. Union occurred in 56 cases (96.5%) after the index procedure. Three patients were bedridden before the injury; the remainder regained full weight-bearing status. The mean duration until full weight-bearing status in these patients was 8.6 weeks (4-13). Early implant failure with proximal dislocation of the screws occurred in two cases (3.5% revision rate). At follow up, 78% had maintained the same social status as before the injury. Fifty-two patients (89%) had regained their previous level of mobility. The mean Barthel index was 85 points (70-100) out of a possible 100, and improved from a mean of 35 points at the start of rehabilitation. It decreased on average by ten points compared to the preoperative status. The mean ''up and go'' time was measured as 21.4 s. In conclusion, polyaxial plates can achieve excellent surgical results. On the other hand, patients with this type of injury exhibit a clear deterioration in their social status, especially regarding lower limb motor function and self independence. PMID- 26815570 TI - Bone Fracture Healing with Umbilico-Placental Mononuclear Cells: A Controlled Animal Study. AB - BACKGROUND: Fracture healing is a significant process in orthopedics. In this controlled animal study, our aimis to expose the healing effects of cord blood umbilico-placental mononuclear cells (UPMNCs) on bone fractures. MATERIALS AND METHODS: Caesarean sections were performed on five pregnant New Zealand rabbits at term. Placentas and cords were collected. Standard closed transverse shaft fractures were created on both tibial bones of 15 baby rabbits. The right tibias were given UPMNCs; the left tibias were the control group. Histological examinations, osteoblast and osteoclast cell counts, and mechanical stabilities were compared. Anchorage of the donor cells was shown by the fluorescence in situ hybridization (FISH) technique. RESULTS: In the group injected with UPMNCs, histopathological fracture healing was faster, osteoblast and osteoclast counts were significantly increased, and the maximum load capacity was higher. The presence of XX and XY chromatins on the same slide revealed the anchorage of female donor cells on male tissues. CONCLUSION: The effects of umbilico-placental mononuclear cells on bone healing are histopathological healing priority, increased osteoblastic and osteoclastic activities (bone turnover), and better mechanical stability. PMID- 26815571 TI - Inframesocolic Abdominal Aortic Injury and Lumbar Vertebral Body Fracture Secondary to Hyperextension with Blunt Trauma. AB - This case study describes an abdominal aortic injury and lumbar vertebral body fracture after blunt trauma. Abdominal aortic pseudoaneurysm is a rare complication of blunt abdominal trauma. Recent data reveal seven other reports in the literature. We describe a case of an inframesocolic abdominal aortic injury and lumbar vertebral body fracture from blunt trauma in a 16-year-old male after a hyperextension injury while body board surfing. PMID- 26815572 TI - Modified Technique of Mesh Hepatorrhaphy for Management of Juxtahepatic Venous Injury in a Case of Blunt Liver Trauma: A Case Report. AB - The liver is the most frequently injured organ in cases of blunt abdominal trauma. Injuries to the caudate lobe are rarely isolated and usually associated with retrohepatic caval injury or hepatic vein injury. The management of the associated vascular injuries is usually difficult owing to the short courses of the hepatic veins and the difficulty in obtaining proximal and distal control of the suprarenal and suprahepatic inferior vena cava - hence the frequency of perihepatic packing in the management of caudate lobe and hepatic venous injuries. We present here a rare case of the failure of perihepatic packing to effectively control hemorrhage from blunt injury to the caudate lobe and retrohepatic vena cava. A case of blunt abdominal trauma with injury to the caudate lobe and retrohepatic venous injury was initially managed with perihepatic packing. The patient developed hemorrhage 48 h after pack removal, which was then successfully managed with mesh hepatorrhaphy of the caudate lobe. PMID- 26815573 TI - MRI Appearance of Nerve Regeneration in a Surgically Repaired Ulnar Nerve. AB - BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) findings for surgical repair of a transected nerve have not been published. We describe the first reported postoperative MR imaging findings of a repaired transected ulnar nerve. METHODS: A patient presented to our institution following surgical repair of a severed ulnar nerve at the level of the forearm. MRI was obtained to evaluate postsurgical outcome and potential complications. RESULTS: Magnetic resonance imaging demonstrates the presence of nerve fascicles that are clearly depicted above and below the level of injury but appear indistinct at the level of transection. CONCLUSION: To our knowledge, the MRI appearance of a repaired transected nerve has not been previously described. We believe that the MRI findings may be used to assess the anatomic progress of nerve healing and, when combined with a series of progressively favorable results from a focused neurologic exam, provide convincing evidence of nerve regeneration. PMID- 26815574 TI - Delayed Chylothorax Following Blunt Chest Trauma. AB - Chylothorax is a very rare disease, and its diagnosis following blunt chest trauma is exceptional. Only a small number of cases have been reported in the literature. We report a case of a male patient involved in a car accident presenting a delayed chylothorax after blunt chest trauma with a bilateral serial rib fracture and fracture of the ninth thoracic vertebrae. The therapy includes thorax drainage, dietary modifications with total parenteral nutrition and, in severe cases, PEEP ventilation. Hematological monitoring is mandatory to detect metabolic abnormalities resulting from chyle loss. Surgical treatment is only required in cases of persistent or increasing intrathoracal chyle flow. Thoracoscopic ligation of the thoracic duct is then required.Severe consequences, such as cardiopulmonary abnormalities and metabolic, nutritional and immunologic disorders, can result from chylothorax. Our patient was treated successfully by chest drainage and parenteral nutrition. PMID- 26815575 TI - Electric-Assisted Capillary Rise Adsorption of Polar and Nonpolar Solvents by Cellulose and Chitosan. AB - Electric-assisted capillary rise adsorption of polar and nonpolar solvents by cellulose and chitosan was studied by employing an electrostatic generator to assist a common capillary rise wetting by taking the anode and cathode electrodes respectively linked to a metal tube charged with samples and the probe solvent. To vary the voltage at 0, 100, 200, and 300 V, respectively, the recorded dynamic adsorption results showed that the cellulose and chitosan both kept a stable adsorption of the nonpolar hexane and diiodomethane, obviously ignoring the voltage increase. Moreover, the hexane amount adsorbed by cellulose and chitosan is similar, while the diiodomethane amount was adsorbed to a greater amount by cellulose as compared with the chitosan corresponding to these two biomaterials based nonpolar components, for example, greater for cellulose and smaller for chitosan. Results also showed that the adsorption of polar water and formamide was gradually increased with the voltage increase, especially for chitosan, to correspond to the polar component of these materials, for example, greater for chitosan and smaller for cellulose. These adsorption behaviors suggested that the application of an extra electric field can only enhance the adsorption of polar solvent, and the molecular structure, for exmaple, the beta-(1-4)-linked d glucosamine units of chitosan, has sensitive electric field responses in polar solvent adsorption as compared with those of the beta(1-4)-linked d-glucose units of cellulose. The reason for the electric adsorption behaviors was known due to the presence of an extra electric-field-induced reduction of the total surface tension of solvent and mainly the polar component. PMID- 26815576 TI - 12th European Congress of Trauma and Emergency Surgery. PMID- 26815578 TI - Association between TNFA Gene Polymorphisms and Helicobacter pylori Infection: A Meta-Analysis. AB - BACKGROUND: Several host genetic factors are thought to affect susceptibility to Helicobacter pylori infection-related diseases, including tumor necrosis factor (TNF)-alpha. Previous studies have evaluated the association between TNFA gene polymorphisms and H. pylori infection, but the results were inconclusive. We conducted this meta-analysis to clarify the association between TNFA polymorphisms and H. pylori infection. METHODS: Published literature within PubMed, Embase, and the Cochrane Library were used in our meta-analysis. Data were analyzed with the Stata13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (CI). RESULTS: A total of 24 studies were included in our study. The TNFA -308G>A polymorphism was associated with decreasing H. pylori infection (AA vs. AG+GG, OR = 0.64, 95% CI = 0.43-0.97; AA vs. GG, OR = 0.64, 95% CI = 0.43-0.97). A significantly decreased risk was also found for 1031T>C polymorphism (CC vs. CT+TT, OR = 0.61, 95% CI = 0.44-0.84). -863C>A polymorphism was associated with increasing risk of H. pylori infection (AA+AC vs. CC, OR = 1.47, 95% CI = 1.16-1.86; A allele vs. C allele, OR = 1.40, 95% CI = 1.14-1.72). There was no significant association between -857C>T polymorphism and H. pylori infection. When stratified analysis was conducted on H. pylori infection detection methods, -857C>T and -863C>A polymorphisms were associated with H. pylori infection for the non-ELISA subgroup. When stratified for ethnicity or study design, -863C>A significantly increased the risk and -1031T>C decreased the risk for the Asian subgroup and hospital-based subgroup. CONCLUSION: Results of our meta-analysis demonstrate that TNFA -308G>A and -1031 T>C polymorphisms may be protective factors against H. pylori infection, and 863C>A may be a risk factor, especially in Asian populations. Further studies with larger sample sizes are required to validate these results. PMID- 26815579 TI - Religiosity as a Moderator of Self-Efficacy and Social Support in Predicting Traumatic Stress Among Combat Soldiers. AB - Based on a sample of 54 Israeli soldiers (51 % non-religious, 49 % religious) surveyed upon their return from combat, this study investigates the moderating role of religiosity as a factor that may strengthen cognitive processing tied to the belief in oneself to persevere (i.e., self-efficacy) after trauma and/or as a factor tied to enhanced external social support that religious individuals in particular may benefit from by their involvement in a religious community. Findings revealed (1) social support was tied to greater resilience within the general sample; (2) religious soldiers were less susceptible to traumatic stress than non-religious soldiers; and (3) religiosity moderated the relationship between self-efficacy and traumatic stress but not the relationship between social support and traumatic stress. Implications of findings are discussed. PMID- 26815581 TI - Transfusion practice in dogs and cats: an Internet-based survey. AB - OBJECTIVE: To characterize and compare current canine and feline transfusion practices at private referral hospitals (PRH) and veterinary teaching hospitals (VTH), including information regarding blood donor screening; blood product collection, storage, and administration; recipient screening; and monitoring during transfusions. DESIGN: Internet-based survey. SUBJECTS: Sixty-five board certified specialist veterinarians, 3 veterinarians, and 5 veterinary technicians from 53 PRH and 20 VTH. METHODS: A survey was disseminated via email LIST-SERVs; 1 survey response per hospital was included. MAIN RESULTS: Survey results revealed that PRH more commonly obtained canine and feline blood products solely from blood banks (P < 0.05) and VTH more commonly used hospital-run donor programs (P < 0.05). Canine cryo-poor plasma was more likely to be stored by VTH compared to PRH (P = 0.018) and VTH were more likely to store canine fresh platelet products for >72 hours (P = 0.046). The use of client-owned canine donors (P = 0.043), administration of precollection 1-deamino-8-d-arginine vasopressin to canine donors (P = 0.041), and storage of blood products in a dedicated refrigerator (P = 0.003) and -20 degrees C or -80 degrees C freezer (P = 0.044) were more common in VTH than PRH. However, the use of a refrigerator freezer (P = 0.001), single bag canine collection systems (P = 0.021), and agglutination cards for feline blood typing (P = 0.032), as well as warming of blood products prior to administration (P = 0.021) were more commonly reported by PRH compared to VTH. CONCLUSIONS: Although some transfusion practices including the method and length of storage of blood products, use and screening of blood donors, and administration methods varied between VTH and PRH, most transfusion practices were similar. The information reported from this survey could aid the development of future veterinary transfusion consensus statements. PMID- 26815580 TI - The Coagulation Factor XIIa Inhibitor rHA-Infestin-4 Improves Outcome after Cerebral Ischemia/Reperfusion Injury in Rats. AB - BACKGROUND AND PURPOSE: Ischemic stroke provokes severe brain damage and remains a predominant disease in industrialized countries. The coagulation factor XII (FXII)-driven contact activation system plays a central, but not yet fully defined pathogenic role in stroke development. Here, we investigated the efficacy of the FXIIa inhibitor rHA-Infestin-4 in a rat model of ischemic stroke using both a prophylactic and a therapeutic approach. METHODS: For prophylactic treatment, animals were treated intravenously with 100 mg/kg rHA-Infestin-4 or an equal volume of saline 15 min prior to transient middle cerebral artery occlusion (tMCAO) of 90 min. For therapeutic treatment, 100 mg/kg rHA-Infestin-4, or an equal volume of saline, was administered directly after the start of reperfusion. At 24 h after tMCAO, rats were tested for neurological deficits and blood was drawn for coagulation assays. Finally, brains were removed and analyzed for infarct area and edema formation. RESULTS: Within prophylactic rHA-Infestin-4 treatment, infarct areas and brain edema formation were reduced accompanied by better neurological scores and survival compared to controls. Following therapeutic treatment, neurological outcome and survival were still improved although overall effects were less pronounced compared to prophylaxis. CONCLUSIONS: With regard to the central role of the FXII-driven contact activation system in ischemic stroke, inhibition of FXIIa may represent a new and promising treatment approach to prevent cerebral ischemia/reperfusion injury. PMID- 26815582 TI - Ninjurin1 suppresses metastatic property of lung cancer cells through inhibition of interleukin 6 signaling pathway. AB - Nerve injury-induced protein 1 (Ninjurin1, Ninj1) is a cell surface molecule that can mediate homophilic adhesion and promote neurite outgrowth from cultured dorsal root ganglion (DRG) neurons. Interestingly, Ninj1 overexpressed in human cancer; however, its role in metastasis is not clear. This study showed that inhibition of Ninj1 promotes lung cancer metastasis through interleukin 6 (IL 6)/STAT3 signaling. Ninj1 levels were relatively low in highly motile lung cancer cells. While inhibition of Ninj1 enhanced cell migration in lung cancer cells, overexpression of Ninj1 significantly suppressed it. We found that inhibition of Ninj1 significantly increased expression and secretion of IL-6 in A549 cells. We also found that inhibition of IL-6 decreased intercellular adhesion molecule 1 (ICAM-1) expression. In addition, inhibition of Ninj1 significantly increased cell motility and invasiveness of lung cancer cells. In an in vivo model, we found that Ninj1 suppression did not affect tumor growth but induced significant increase in incidence of lung metastasis, and sizes and number of tumor nodules. Taken together, our data clearly demonstrate that Ninj1 suppresses migration, invasion and metastasis of lung cancer via inhibition of the IL-6 signaling pathway in vitro and in vivo. PMID- 26815583 TI - [Antiphospholipid syndrome and pregnancy]. AB - Antiphospholipid syndrome (APS) is the association of antiphospholipid antibodies with thromboses and/or obstetric morbidity. Obstetric morbidity includes recurrent first trimester loss, stillbirth, intrauterine death, preeclam-psia, premature birth and fetal growth restriction. Although current treatment regimens including aspirin and low-molecular weight heparin have improved pregnancy outcomes, 30% of affected women have pregnancy complica-tions. Women with APS are therefore high-risk pregnancies who should be monitored in specialist centres according to international standards. PMID- 26815584 TI - [Immunotherapy for Alzheimer's disease]. AB - Passive anti-beta-amyloid (Abeta) immunotherapy has been shown to clear brain Abeta deposits. Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing. Subsequent analysis of pooled data from both phase III trials with solanezumab showed a reduction in cognitive decline in patients with mild AD. Solanezumab and new monoclonal antibodies are being tested in patients with prodromal and preclinical AD in search for a disease-modifying treatment. PMID- 26815585 TI - [Initial evaluation and management of paroxysmal supraventricular tachycardia]. AB - The paroxysmal supraventricular tachycardias (SVT) are commonly encountered arrhythmias and include atrioventricular nodal re-entrant tachycardia, atrioventricular reciprocating tachycardia, and focal atrial tachycardia. These tachycardias share several clinical features as well as similar management strategies. The probable mechanism of paroxysmal SVT can often be diagnosed from the clinical findings and a 12-lead ECG. This review describes the initial evaluation and treatment of patients with paroxysmal SVT, including distinctive features from the most important differential diagnoses. PMID- 26815586 TI - [Acute renal failure after participation in high endurance sport]. AB - In two case report Danish men, who were experienced amateur athletes, suffered from severe reversible acute renal failure after participation in a trail run and a long-distance bike race. For both men the treatment was dialysis, diuretics and fluid therapy. The cause of renal failure was never fully clarified. Both men consumed non-steroidal antiinflammatory drugs during the race, had high levels of creatinine kinase and were dehydrated. Possibly, these factors together resulted in "the perfect storm" and caused acute reversible renal failure. PMID- 26815587 TI - [Retracted: Placental-site trophoblastic tumour]. PMID- 26815588 TI - Morphine Attenuated the Cytotoxicity Induced by Arsenic Trioxide in H9c2 Cardiomyocytes. AB - Arsenic trioxide (ATO) is an efficient drug for the treatment of the patients with acute promyelocytic leukemia (APL). Inhibition of proliferation as well as apoptosis, attenuation of migration, and induction of differentiation in tumor cells are the main mechanisms through which ATO acts against APL. Despite advantages of ATO in treatment of some malignancies, certain harmful side effects, such as cardiotoxicity, have been reported. It has been well documented that morphine has antioxidant, anti-apoptotic, and cytoprotective properties and is able to attenuate cytotoxicity. Therefore, in this study, we aimed to investigate the protective effects of morphine against ATO toxicity in H9c2 myocytes using multi-parametric assay including thiazolyl blue tetrazolium bromide (MTT) assay, reactive oxygen species (ROS) generation, caspase 3 activity, nuclear factor kappa B (NF-kappaB) phosphorylation assay, and expression of apoptotic markers. Our results showed that morphine (1 MUM) attenuated cytotoxicity induced by ATO in H9c2 cells. Results of this study suggest that morphine may have protective properties in management of cardiac toxicity in patients who receive ATO as an anti-cancer treatment. PMID- 26815589 TI - Molecular-Scale Investigation with ESI-FT-ICR-MS on Fractionation of Dissolved Organic Matter Induced by Adsorption on Iron Oxyhydroxides. AB - Adsorption by minerals is a common geochemical process of dissolved organic matter (DOM) which may induce fractionation of DOM at the mineral-water interface. Here, we examine the molecular fractionation of DOM induced by adsorption onto three common iron oxyhydroxides using electrospray ionization coupled with Fourier-transform ion cyclotron resonance mass spectrometry (ESI-FT ICR-MS). Ferrihydrite exhibited higher affinity to DOM and induced more pronounced molecular fractionation of DOM than did goethite or lepidocrocite. High molecular weight (>500 Da) compounds and compounds high in unsaturation or rich in oxygen including polycyclic aromatics, polyphenols and carboxylic compounds had higher affinity to iron oxyhydroxides and especially to ferrihydrite. Low molecular weight compounds and compounds low in unsaturation or containing few oxygenated groups (mainly alcohols and ethers) were preferentially maintained in solution. This study confirms that the double bond equivalence and the number of oxygen atoms are valuable parameters indicating the selective fractionation of DOM at mineral and water interfaces. The results of this study provide important information for further understanding the behavior of DOM in the natural environment. PMID- 26815590 TI - Pharmacokinetic Studies of Oxathio-Heterocycle Fused Chalcones. AB - BACKGROUND AND OBJECTIVES: Chalcone constitutes one of the most used molecular frameworks in medicinal chemistry and its derivatives exhibit a broad spectrum of biological activities. Low absolute bioavailability, poor distribution, intensive metabolism and elimination of chalcones are the main problems in designing new drugs based on their structure. One of the fundamental steps in evaluation of drug candidates is a comparative analysis of pharmacokinetic parameters. The aim of the studies was the pharmacokinetic characterization of the selected oxathio heterocycle fused chalcones. METHODS: The pharmacokinetic parameters of 19 compounds were reported. The analyzed chalcones were examined after a single intravenous administration to forty 7-week-old mature male rats of Wistar stock. Pharmacokinetic analysis was performed independently using SHAM (slopes, highest, amounts, and moments) and the two-compartment model. Basic physiochemical parameters were calculated. The bioanalytical methods were validated in terms of repeatability, linearity, accuracy, precision, and selectivity. RESULTS: The pharmacokinetics of the examined group of chalcones are compatible with the two compartment model. The physicochemical characteristics of this group are quite homogeneous. The kinetics of the examined chalcones are indicative of a distribution to the tissue compartment with the predominance of a rate constant from central to peripheral compartments (k12) over the rate constant from peripheral to central compartments (k21). The elimination from the central compartment (k10) is higher than the transfer from the central compartment to the tissues (k10 > k12) in almost all examined cases. CONCLUSIONS: The presented group of compounds may form a starting point for studies into drugs treating autoimmune diseases of the gastro-intestinal tract. PMID- 26815591 TI - Near-infrared unsymmetrical blue and green squaraine sensitizers. AB - Two novel panchromatic asymmetrical squaraine sensitizers (SPSQ1 and SPSQ2) have been synthesized, characterized and effectively used for TiO2-based dye sensitized solar cells. In a solution, both dyes display a highly intense near-IR absorption (SPSQ1; 651 nm and SPSQ2; 692 nm), the red shifted absorption of SPSQ2 was attributed to the incorporation of the auxiliary acceptor dicyanovinyl unit on the squaraine moiety. Interestingly, the dicyanovinyl unit lowered the LUMO level of SPSQ2, which decreased the band gap and red shifted the absorption when compared to SPSQ1. These dyes possess suitable HOMO and LUMO levels to work as efficient sensitizers in DSSCs. The experimental trends in their optical and electrochemical properties are well matched with the theoretical calculations modeled by TDDFT. The blue and green color of the devices showed their complementary absorption and harvest a greater number of photons from solar flux. Under standard global AM 1.5 G solar conditions, the DSSC based on SPSQ2 exhibited a high power conversion efficiency of 3.1% with a high short circuit current density (JSC) attributed to the broadening of the IPCE spectra in the UV vis and near-IR regions when compared to SPSQ1 (2.5%). PMID- 26815592 TI - Kidney stone disease. PMID- 26815593 TI - Atorvastatin treatment is associated with increased BDNF level and improved functional recovery after atherothrombotic stroke. AB - BACKGROUND: Statins have a positive impact on ischemic stroke outcome. It has been reported that statin have neuroprotective function after ischemic stroke in addition to lipid-lowering effect in animal model. However, the neuroprotective function of statin after stroke has not been confirmed in clinical studies. The aim of this study was to evaluate in a clinical model if statins induce neuroprotection after stroke. We, therefore, assessed serum brain-derived neurotrophic factor (BDNF) levels and functional recovery in atherothrombotic stroke patients and investigated their relationship with atorvastatin treatment. METHODS: Seventy-eight patients with atherothrombotic stroke were enrolled and randomly assigned to atorvastatin treatment group or placebo control group. Neurological function after stroke was assessed with the National Institutes of Health Stroke Scale, modified Rankin Scale (mRS) and Barthel Index (BI). The serum BDNF levels were both measured at 1 day and 6 weeks after stroke. Linear regression was used to assess the association between BDNF levels and neurological function scores. RESULTS: The mRS and BI were markedly improved in the atorvastatin group when compared to placebo at 6 weeks after stroke. The serum BDNF levels in atorvastatin group were significantly elevated by 6 weeks after stroke and higher than the BDNF levels in controls. In addition, the serum BDNF levels significantly correlated with mRS and BI after stroke. Our results demonstrated that atorvastatin treatment was associated with the increased BDNF level and improved functional recovery after atherothrombotic stroke. CONCLUSION: This study indicates that atorvastatin-related elevation in the BDNF level may promote functional recovery in stroke patients. PMID- 26815594 TI - The Dimensionality Of Psychopathology Descriptors. AB - This study identified five stable dimensions that judges utilized in making similarity judgments of a set of 26 psychopathology descriptors from a diverse domain representing traditional psychopathology descriptions such as lay labels, and diagnostic categories from the second edition of the Diagnostic and Statistical Manual (DSM II), as well as stimuli from a new nosology of psychopathology based on behavioral descriptions derived from a technique known as modal profile analysis. These five dimensions were interpreted as: Mental Illness, Social vs. Psychological Deviance, Depression vs. Impulse Control, Anxiety vs. Impulse Control, and Paranoid vs. Impulse Control. Results did not, overall, support the superiority of the DSM II descriptors over labels, nor the beneficial influence of diagnostic qualifiers, but did suggest that specific personality information, as exemplified in the modal profile stimuli, reduces the influence of stigmatizing conceptualizations on psychopathology judgments. PMID- 26815595 TI - Applications Of Nonlinear Principal Components Analysis To Behavioral Data. AB - A quadratic function was derived from variables believed to be nonlinearly related. The method was suggested by Gnanadesikan (1977) and based on an early paper of Karl Pearson (1901) (which gave rise to principal components), in which Pearson demonstrated that a plane of best fit to a system of points could be elicited from the elements of the eigenvector associated with the smallest eigenvalue of the covariance matrix. PMID- 26815596 TI - An Examination Of The Validity Of Two Models Of Attitude. AB - A structural equation methodology is used to assess the reliability and validity of expectancy-value and semantic differential measures of attitude toward the act of donating blood. Hypotheses as to the internal consistency and the convergent, concurrent, discriminant, predictive, and nomological validities of responses are tested in the context of a quasi-experiment performed on 284 students, faculty, and staff. Semantic differential attitudes are found to exist as unidimensional responses while expectancy-value attitudes are found to occur as multidimensional reactions. However, although both operationalizations achieve convergent, concurrent, discriminant, and predictive validity, the nomological validity of attitude is brought into question. The extent of past behavior and the elapsed time since performance of that behavior appear to offer the greatest explanatory content for subsequent behavioral intentions. Finally, the role of personal and social normative beliefs as copredictors of intentions along with attitude and past behavior is also investigated. The findings are interpreted from attitude, learning, and attribution theory arguments. PMID- 26815597 TI - The Structure Of The Eysenck Personality Inventory: A Comparison Between Simple And More Complex Analyses Of A Multiple Scale Questionnaire. AB - Responses of 392 students to the Eysenck Personality Inventory were analyzed using conventional factor-analytic techniques and a nonmetric multidimensional scaling method. Rotating the first two factors gave a result clearly comparable with an earlier third-order analysis, while a three-factor rotation neatly clustered the original Extraversion, Neuroticism, and Lie scale items. A three dimensional non-metric analysis appeared to provide no more information for users of the questionnaire than was given by a comparable two-dimensional analysis which had produced a solution closely resembling that of the two-factor rotation. The conclusion reached was that psychometrically useful information may be more readily revealed by simple and rationally restricted analyses than by exhaustive, more complex, and higher order solutions. PMID- 26815598 TI - Personality Matched Across Media In A Large High-School Sample. AB - Forms A and B of the High-School Personality Questionnaire and the complete Objective-Analytic Test Kit were administered to 840 boys aged 12-18. At issue was the alignment of second-stratum factors from the questionnaire data with the first-stratum factors from the O-A data. A salient relationship in the expected direction was found only for Anxiety (Q11, U124). Among other such relationships were that of Exvia (Q1) with U121 (Exuberance) and Tough Poise (Q111, Cortertia) with U125 (Realism). PMID- 26815599 TI - A Review Of Monte Carlo Tests Of Cluster Analysis. AB - A review of Monte Carlo validation studies of clustering algorithms is presented. Several validation studies have tended to support the view that Ward's minimum variance hierarchical method gives the best recovery of cluster structure. However, a more complete review of the validation literature on clustering indicates that other algorithms may provide better recovery under a variety of conditions. Applied researchers are cautioned concerning the uncritical selection of Ward's method for empirical research. Alternative explanations for the differential recovery performance are explored and recommendations are made for future Monte Carlo experiments. PMID- 26815600 TI - Localized surface plasmons in vibrating graphene nanodisks. AB - Localized surface plasmons are confined collective oscillations of electrons in metallic nanoparticles. When driven by light, the optical response is dictated by geometrical parameters and the dielectric environment and plasmons are therefore extremely important for sensing applications. Plasmons in graphene disks have the additional benefit of being highly tunable via electrical stimulation. Mechanical vibrations create structural deformations in ways where the excitation of localized surface plasmons can be strongly modulated. We show that the spectral shift in such a scenario is determined by a complex interplay between the symmetry and shape of the modal vibrations and the plasmonic mode pattern. Tuning confined modes of light in graphene via acoustic excitations, paves new avenues in shaping the sensitivity of plasmonic detectors, and in the enhancement of the interaction with optical emitters, such as molecules, for future nanophotonic devices. PMID- 26815601 TI - Risk of End-Stage Renal Disease in Patients With Lupus Nephritis, 1971-2015: A Systematic Review and Bayesian Meta-Analysis. AB - OBJECTIVE: End-stage renal disease (ESRD) is a major consequence of lupus nephritis, but how this risk has changed over time is unknown. We conducted this systematic review to examine changes in ESRD among adults with lupus nephritis from 1971 to 2015 and to estimate risks of ESRD among contemporary patients. METHODS: We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for cohort studies and clinical trials on ESRD in adults with lupus nephritis. We analyzed studies from developed and developing countries separately. The outcome was probability of ESRD at 5, 10, and 15 years of lupus nephritis. RESULTS: We included 187 articles that reported on 18,309 patients. In developed countries, the 5-year risk of ESRD decreased from 16% (95% confidence interval [95% CI] 14-17%) in 1970-1979 to 11% (95% CI 10-12%) in the mid-1990s and then plateaued. ESRD risks at 10 years and 15 years showed steeper declines in the 1970s and 1980s but also plateaued in 1993-1997, with a notable increase in the late 2000s. The decrease in risk after 1980 coincided with increased use of cyclophosphamide. The 15-year ESRD risk was higher in developing countries than in developed countries. Patients with class IV lupus nephritis had the greatest risk of ESRD, with a 15-year risk of 44% during the 2000s. CONCLUSION: Risks of ESRD in lupus nephritis improved between the 1970s and the mid-1990s and then plateaued, with an increase in the late 2000s. This pattern suggests limitations in the effectiveness of, or access to, current treatments. PMID- 26815603 TI - Ionic Grease Lubricants: Protic [Triethanolamine][Oleic Acid] and Aprotic [Choline][Oleic Acid]. AB - Ionic liquid lubricants or lubricant additives have been studied intensively over past decades. However, ionic grease serving as lubricant has rarely been investigated so far. In this work, novel protic [triethanolamine][oleic acid] and aprotic [choline][oleic acid] ionic greases are successfully synthesized. These ionic greases can be directly used as lubricants without adding thickeners or other additives. Their distinct thermal and rheological properties are investigated and are well-correlated to their tribological properties. It is revealed that aprotic ionic grease shows superior temperature- and pressure tolerant lubrication properties over those of protic ionic grease. The lubrication mechanism is studied, and it reveals that strong physical adsorption of ionic grease onto friction surface plays a dominating role for promoted lubrication instead of tribo-chemical film formation. PMID- 26815604 TI - SAXS Combined with UV-vis Spectroscopy and QELS: Accurate Characterization of Silver Sols Synthesized in Polymer Matrices. AB - The present work demonstrates a validation of small-angle X-ray scattering (SAXS) combining with ultra violet and visible (UV-vis) spectroscopy and quasi-elastic light scattering (QELS) analysis for characterization of silver sols synthesized in polymer matrices. Polymer matrix internal structure and polymer chemical nature actually controlled the sol size characteristics. It was shown that for precise analysis of nanoparticle size distribution these techniques should be used simultaneously. All applied methods were in good agreement for the characterization of size distribution of small particles (less than 60 nm) in the sols. Some deviations of the theoretical curves from the experimental ones were observed. The most probable cause is that nanoparticles were not entirely spherical in form. PMID- 26815605 TI - A multi-subband Monte Carlo study on dominance of scattering mechanisms over carrier transport in sub-10-nm Si nanowire FETs. AB - Dominance of various scattering mechanisms in determination of the carrier mobility is examined for silicon (Si) nanowires of sub-10-nm cross-sections. With a focus on p-type channels, the steady-state hole mobility is studied with multi subband Monte Carlo simulations to consider quantum effects in nanoscale channels. Electronic structures of gate-all-around nanowires are described with a 6-band k . p model. Channel bandstructures and electrostatics under gate biases are determined self-consistently with Schrodinger-Poisson simulations. Modeling results not only indicate that the hole mobility is severely degraded as channels have smaller cross-sections and are inverted more strongly but also confirm that the surface roughness scattering degrades the mobility more severely than the phonon scattering does. The surface roughness scattering affects carrier transport more strongly in narrower channels, showing ~90 % dominance in determination of the mobility. At the same channel population, [110] channels suffer from the surface roughness scattering more severely than [100] channels do, due to the stronger corner effect and larger population of carriers residing near channel surfaces. With a sound theoretical framework coupled to the spatial distribution of channel carriers, this work may present a useful guideline for understanding hole transport in ultra-narrow Si nanowires. PMID- 26815602 TI - An Empirical Polarizable Force Field Based on the Classical Drude Oscillator Model: Development History and Recent Applications. AB - Molecular mechanics force fields that explicitly account for induced polarization represent the next generation of physical models for molecular dynamics simulations. Several methods exist for modeling induced polarization, and here we review the classical Drude oscillator model, in which electronic degrees of freedom are modeled by charged particles attached to the nuclei of their core atoms by harmonic springs. We describe the latest developments in Drude force field parametrization and application, primarily in the last 15 years. Emphasis is placed on the Drude-2013 polarizable force field for proteins, DNA, lipids, and carbohydrates. We discuss its parametrization protocol, development history, and recent simulations of biologically interesting systems, highlighting specific studies in which induced polarization plays a critical role in reproducing experimental observables and understanding physical behavior. As the Drude oscillator model is computationally tractable and available in a wide range of simulation packages, it is anticipated that use of these more complex physical models will lead to new and important discoveries of the physical forces driving a range of chemical and biological phenomena. PMID- 26815606 TI - Synthesis of Mesoporous ZnO Nanosheets via Facile Solvothermal Method as the Anode Materials for Lithium-ion Batteries. AB - Mesoporous ZnO nanosheets are synthesized through a room temperature solvothermal method. Transmission and scanning electronic microscopy observations indicate that as-prepared ZnO hierarchical aggregates are composed and assembled by nanosheets with a length of 1-2 MUm and a thickness of 10-20 nm, and interlaced ZnO nanosheets irregularly stack together, forming a three-dimensional network. Furthermore, large mesopores are embedded in the walls of ZnO nanosheets, confirmed by Brunauer-Emmett-Teller (BET) measurement. Accordingly, the resulting ZnO anode exhibits a high and stable specific discharge capacity of 421 mAh g(-1) after 100 cycles at 200 mA g(-1) and a good rate capability. Such electrochemical performance could be attributed to the multiple synergistic effects of its mesoporous nanosheet structure, which can not only provide a large specific surface area for lithium storage, but also favor the ion transport and electrolyte diffusion. PMID- 26815607 TI - Ion-Beam-Directed Self-Ordering of Ga Nanodroplets on GaAs Surfaces. AB - Ordered nanodroplet arrays and aligned nanodroplet chains are fabricated using ion-beam-directed self-organization. The morphological evolution of nanodroplets formed on GaAs (100) substrates under ion beam bombardment is characterized by scanning electron microscopy and atomic force microscopy. Ordered Ga nanodroplets are self-assembled under ion beam bombardment at off-normal incidence angles. The uniformity, size, and density of Ga nanodroplets can be tuned by the incident angles of ion beam. The ion beam current also plays a critical role in the self ordering of Ga nanodroplets, and it is found that the droplets exhibit a similar droplet size but higher density and better uniformity with increasing the ion beam current. In addition, more complex arrangements of nanodroplets are achieved via in situ patterning and ion-beam-directed migration of Ga atoms. Particularly, compared to the destructive formation of nanodroplets through direct ion beam bombardment, the controllable assembly of nanodroplets on intact surfaces can be used as templates for fabrication of ordered semiconductor nanostructures by droplet epitaxy. PMID- 26815608 TI - Holographic and e-Beam Image Recording in Ge5As37S58-Se Nanomultilayer Structures. AB - Processes of e-beam and holographic recording of surface relief structures using Ge5As37S58-Se multilayer nanostructures as registering media were studied in this paper. Optical properties of Ge5As37S58, Se layers, and Ge5As37S58-Se multilayer nanostructures were investigated. Spectral dependencies of refractive index were analyzed within the frames of single oscillator model. Values of optical band gaps for Ge5As37S58, Se layers, and Ge5As37S58-Se multilayer nanostructures were obtained from Tauc dependencies. Using e-beam and holographic recording, diffraction gratings were fabricated in Ge5As37S58-Se multilayer nanostructures. Images of Ukraine and Moldova state emblems were obtained by e-beam recording. Image size consisted of 512 * 512 pixels (size of 1 pixel was ~2 MUm). Ge5As37S58 Se multilayer nanostructures are perspective for the direct recording of holographic diffraction gratings and other optical elements. PMID- 26815609 TI - Wavelength-tunable sources of entangled photons interfaced with atomic vapours. AB - The prospect of using the quantum nature of light for secure communication keeps spurring the search and investigation of suitable sources of entangled photons. A single semiconductor quantum dot is one of the most attractive, as it can generate indistinguishable entangled photons deterministically and is compatible with current photonic-integration technologies. However, the lack of control over the energy of the entangled photons is hampering the exploitation of dissimilar quantum dots in protocols requiring the teleportation of quantum entanglement over remote locations. Here we introduce quantum dot-based sources of polarization-entangled photons whose energy can be tuned via three-directional strain engineering without degrading the degree of entanglement of the photon pairs. As a test-bench for quantum communication, we interface quantum dots with clouds of atomic vapours, and we demonstrate slow-entangled photons from a single quantum emitter. These results pave the way towards the implementation of hybrid quantum networks where entanglement is distributed among distant parties using optoelectronic devices. PMID- 26815611 TI - Novel mesoporous P-doped graphitic carbon nitride nanosheets coupled with ZnIn2S4 nanosheets as efficient visible light driven heterostructures with remarkably enhanced photo-reduction activity. AB - In this report, we rationally designed and fabricated P-C3N4/ZnIn2S4 nanocomposites by in situ immobilizing ZnIn2S4 nanosheets onto the surface of mesoporous P-doped graphite carbon nitrogen (P-C3N4) nanosheets in a mixed solvothermal environment; their application to the photoreduction of 4 nitroaniline was used to estimate the photocatalytic performance. Different to the template route, here the mesoporous P-C3N4 nanosheets were prepared with a template-free strategy. The as-fabricated P-C3N4/ZnIn2S4 nanocomposites were systematically characterized by analyzing the phase structure, chemical components, electronic and optical properties and separation of charge carrier pairs. More importantly, these P-C3N4/ZnIn2S4 heterostructures have been proven to be highly efficient visible light responsive photocatalysts for photo reduction, and meanwhile exhibit excellent photo-stability during recycling runs. The sufficient evidence reveals that the significantly improved photocatalytic performance is mainly attributed to the more efficient charge carrier separation based on the construction of a close heterogeneous interface. This work may provide new insights into the utilization of P-C3N4/ZnIn2S4 nanocomposites as visible light driven photocatalysts for comprehensive organic transformations in the field of fine chemical engineering. PMID- 26815612 TI - Focus on Elbow Fractures. PMID- 26815610 TI - Skeletal Characterization of Smurf2-Deficient Mice and In Vitro Analysis of Smurf2-Deficient Chondrocytes. AB - Overexpression of Smad ubiquitin regulatory factor 2 (Smurf2) in chondrocytes was reported to cause spontaneous osteoarthritis (OA) in mice. However, it is unclear whether Smurf2 is involved in bone and cartilage homeostasis and if it is required for OA pathogenesis. Here we characterized age-related changes in the bone and articular cartilage of Smurf2-deficient (MT) mice by microCT and histology, and examined whether reduced Smurf2 expression affected the severity of OA upon surgical destabilization of the medial meniscus (DMM). Using immature articular chondrocytes (iMAC) from MT and wild-type (WT) mice, we also examined how Smurf2 deficiency affects chondrogenic and catabolic gene expressions and Smurf2 and Smurf1 proteins upon TGF-beta3 or IL-1beta treatment in culture. We found no differences in cortical, subchondral and trabecular bone between WT and MT in young (4 months) and old mice (16-24 months). The articular cartilage and age-related alterations between WT and MT were also similar. However, 2 months following DMM, young MT showed milder OA compared to WT (~70% vs ~30% normal or exhibiting only mild OA cartilage phenotype). The majority of the older WT and MT mice developed moderate/severe OA 2 months after DMM, but a higher subset of aged MT cartilage (27% vs. 9% WT) remained largely normal. Chondrogenic gene expression (Sox9, Col2, Acan) trended higher in MT iMACs than WT with/without TGF beta3 treatment. IL-1beta treatment suppressed chondrgenic gene expression, but Sox9 expression in MT remained significantly higher than WT. Smurf2 protein in WT iMACs increased upon TGF-beta3 treatment and decreased upon IL-1beta treatment in a dose-dependent manner. Smurf1 protein elevated more in MT than WT upon TGF beta3 treatment, suggesting a potential, but very mild compensatory effect. Overall, our data support a role of Smurf2 in regulating OA development but suggest that inhibiting Smurf2 alone may not be sufficient to prevent or consistently mitigate post-traumatic OA across a broad age range. PMID- 26815613 TI - The Role of Total Elbow Arthroplasty in Complex Distal Humeral Fractures. AB - Fractures of the distal humerus are routinely treated by open reduction and internal fixation in an attempt to retain a painless, stable and functional joint. However, results of fixation, even with advances in plate technology, are still dependent on screw purchase and bone quality. Reported results, over the past decade, now support consideration of primary total elbow arthroplasty, in cases of highly comminuted distal humeral fractures, especially in the elderly who have low physical demands, or in those who have significant pre-existing inflammatory joint disease resulting in marked joint destruction. PMID- 26815614 TI - Radial Head Fractures: Indications and Technique for Primary Arthroplasty. AB - The treatment of complex radial head fractures remains a challenge for the orthopedic surgeon. Novel implants and improved surgical techniques have made reconstruction of the radial head with open reduction and internal fixation possible in most cases. However, extremely comminuted radial head fractures with associated instabilities still require replacement of the radial head with a prosthesis to allow rehabilitation with early motion of the elbow, and thereby optimizing the functional results of these potentially devastating injuries. In this article we discuss the surgical considerations related to radial head replacement, encompassing the indications for radial head arthroplasty, implant selection, surgical technique, rehabilitation protocols, and complications related to radial head prosthesis. PMID- 26815615 TI - Fractures of the Coronoid Process of the Ulna: Which Ones to Fix and Which Ones to Leave Alone: A Review. AB - The coronoid process of the ulna forms the anterior boundary of the trochlear notch and is crucial for elbow stability. Coronoid fractures are uncommon and they occur in aproximately 10% of elbow dislocations. They are mostly associated with ligamentous and capsular disruptions as well as concomitant fractures. Posterior elbow dislocations, combined with fractures of the coronoid and the radial head are known as the terrible-triad of the elbow. These injuries result in instability of the elbowjoint and, if not treated properly, lead to recurrent dislocations that can cause further damage. Depending on the pattern of the injury and the quality of the bone, the surgeon has to choose from a variety of treatment options. Large coronoid fragments and other associated fractures are ideally treated by ORIF (open reduction internal fixation); a prosthetic radial head replacement may be favorable if a comminuted radial head fracture is not reconstructable. Isolated small coronoid process fractures can be treated non operatively with satisfactory results. Although rough guidelines can bemade, it is important to view each patient's elbow injury individually and then make a specific treatment plan. Data on treatment results are sparse. Improved understanding of coronoid fractures and their management will result in better outcomes and decrease possible complications including a certain degree of stiffness, neuropathy and arthrosis. PMID- 26815616 TI - Current Concepts: Simple and Complex Elbow Dislocations - Acute and Definitive Treatment. AB - Dislocations of the elbow account for 20% of all dislocations. Thus, after the shoulder, the elbow joint is the joint most frequently afflicted by dislocations. A distinction is made between simple elbowdislocations without associated fractures and fracture-dislocations of the elbow, which are frequently referred to as complex elbow dislocations. Treatment principles are reduction of the joint, stabilization of associated fractures, and early motion. Ligament repairs or reconstruction and hinged external fixators are necessary in some cases to restore stability for early motion. In general, simple dislocations have a better prognosis than complex dislocations. PMID- 26815617 TI - Diagnostic Approach for Suspected Scaphoid Fractures in Children. AB - Scaphoid fractures in children are rare injuries. A complete scaphoid waist fracture in a 13-year-old boy after fall on the extended wrist is reported. Following early diagnosis by MRI, the fracture healed uneventful with conservative treatment. The appropriate diagnostic approach and the advantages of MRI for suspected scaphoid fractures in children are discussed. PMID- 26815618 TI - Hand Trauma Pitfalls: A Retrospective Study of Fight Bites. AB - Clench fist or fight bite injuries are associated with some of the worst types of infective complications but their mechanism is often poorly understood. In a retrospective case series, 34 patients seen between 1998 and 2004 presented to a local hand surgery unit with confirmed human bite hand injuries. Seventy-six percent presented with infective complications with a mean delay in presentation of 4 days. Eighty percent of patients were clench fist injuries (CFI) (open joints in 59% and tendon injuries in 63%). Using an aggressive treatment policy including early surgical and antibiotic intervention, most patients achieved good results functionally (full range of movement was achieved in 83% of those with CFI which completed follow-up (44%)). High rates of non-compliance and incomplete follow-up was noted. Major long-term complications including limited range of movement and osteomyelitis was low and suggests the policy of prompt and comprehensive surgical and medical intervention is the optimal treatment option. A brief but in-depth discussion of the specific anatomical pitfalls is included. PMID- 26815619 TI - Cytokine Responses to Glucocorticoids and Surgery : A Randomized Controlled Trial. AB - PURPOSE: This prospective randomized study was designed to evaluate the implication of high preoperative doses of glucocorticoids on the cytokine responses after surgical correction in patients with ankylosing spondylitis. PATIENTS AND METHODS: In 20 consecutive patients an extending osteotomy of the lumbar spine was done by a wedge excision. In a random manner, 10 of the patients were given 10 mg/kg of methylprednisolone ("Solum-Medrol", Pharmacia & Upjohn, Stockholm, Sweden) preoperatively. The control patients received the same amount of saline. Arterial blood was sampled before and at the end of operation and at 4 and 24 h postoperatively and analyzed for pro- and antiinflammatory cytokines. RESULTS: Surgery induced non-significant increases in TNF-alpha and IL-1-beta and significant increases in IL-6, IL-8, IL-10 and sTNF-R1 in both patient groups. Glucocorticoids significantly reduced increases in IL-6 and IL-8. On the other hand, increases in IL-10 and sTNF-R1 were significantly enhanced by corticoids. In both groups CRP was significantly increased at 24 h after surgery, but the increments were significantly reduced by corticoids. CONCLUSION: This study shows that surgery adds a complexity to cytokine productions in patients with ankylosing spondylitis, and that the balance of these cytokines is significantly influenced by glucocorticoids. PMID- 26815620 TI - The Prognostic Significance of Pulmonary Contusions on Initial Chest Radiographs in Blunt Trauma Patients. AB - OBJECTIVE: The importance of immediate versus delayed pulmonary contusions among severely injured blunt trauma patients is unknown. We hypothesized that patients with pulmonary contusions apparent on initial chest radiographs have higher rates of mortality and acute respiratory distress syndrome than patients who have delayed radiographic changes of pulmonary contusions. DESIGN: Retrospective cohort study. SETTING: Level 1 designated trauma centre in Ontario Canada. METHODS: Eligible cases were identified through the hospital trauma registry over a 5-year period. All intubated severe trauma patients (ISS >= 16) with a discharge diagnosis of pulmonary contusion who presented within 2 h of injury time, were included. All cases had chest CT performed within 24 h of admission with reported findings consistent with pulmonary contusions. Patients with pulmonary contusions apparent on initial chest radiographs (CXR+) were compared with patients with delayed initial radiographic findings (CXR-). Primary outcomes were assessed by logistic regression controlling for covariates of interest. RESULTS: A total of 135 intubated trauma patients with pulmonary contusions were identified over the study period. Only 52% of these patients had contusions apparent on initial chest radiograph. The overall mortality was higher in CXR+ group compared with those in CXR- group (43% vs. 25% p = 0.02). In multivariable analyses controlling for injury severity, age, sex and head injury, the CXR+ group was associated with significantly increased odds of mortality and ARDS (odds ratio for CXR+ vs. CXR- 4.19, 95%CI 1.54-11.45, p < 0.01). CONCLUSION: Amongst intubated blunt trauma patients with confirmed pulmonary contusions diagnosis, an initial chest radiograph that reveals immediate pulmonary contusion is associated with higher mortality and ARDS compared with the absence of such findings. This suggests that the initial chest radiographs have prognostic significance in relation to pulmonary contusions due to blunt trauma. PMID- 26815621 TI - Examining the Impact of Renal Trauma Guidelines on Urologists in UK. AB - OBJECTIVE: To investigate whether urologists in UK utilise and adhere to recently published renal trauma guidelines. METHODS: A one-page anonymous questionnaire was created based on recently published guidelines. Thirteen questions were used to investigate the current patterns of practice. The questionnaire was posted to 500 consultants in UK. RESULTS: Out of 500 questionnaires, 152 (30%) were returned; 109 (70%) respondents saw an estimated five or less cases of renal trauma per year; 104 (71%) respondents used guidelines but these differed; 79 (52%) respondents believed that the published guidelines were appropriate for UK practice; 8 (5%) did not feel that they were appropriate and 48 (32%) were unsure, and 30 (20%) used local guidelines. In stable patients with dipstick hematuria, 121 (80%) respondents requested imaging with ultrasound (76) the most popular. In stable patients with gross hematuria, all respondents requested imaging with CT scanning (126) the most popular. In stable children with suspected renal trauma, all respondents who managed pediatric cases would request imaging. Re-imaging following initial ultrasound was common. Imaging was described as easy or possible to obtain during regular working hours by 147 (97%) respondents. This fell to 131 (86%) out of hours with 14 (9%) respondents having difficulty with obtaining imaging. Only 27 (18%) respondents had interdepartmental protocols to facilitate the imaging process in suspected renal trauma. CONCLUSION: Only 74 (50%) responding urologists utilized the recently published guidelines in the management of renal trauma, and adherence to the recommendations - by those urologists who claimed to use the guidelines - was very variable. To facilitate the best practice in the management of renal trauma, it would be ideal if urologists and trauma surgeons were encouraged to adhere to established guidelines. As diagnostic imaging has a crucial role in the majority of cases, informed discussion with the local radiology department would probably help in achieving the standards required. PMID- 26815622 TI - Intracranially Retained Sewing Needle in a Child: Does the Rust on the Needle Have any Implication? AB - A penetrating injury with a sewing needle is a rare phenomenon. The pathophysiological mechanism of late epilepsy after penetrating injuries is not clear. A 10-year-old female child had a seizure. An X-ray study of the skull and the cranial computed tomography scans showed a foreign object retained in the skull cavity. She was intact on neurological examination. Electroencephalogram (EEG) showed that there was bioelectrical disorganization in both hemispheres, being more prominent on the left side. A right posterior frontal median craniotomy was performed in order not to retract the left hemisphere within the interhemispheric fissure and the sewing needle was removed successfully. The sewing needle was rusted. The reason for the patient's seizure, 10 years after the injury, may be the corrosion of the sewing needle and rust formation in this case. PMID- 26815623 TI - Hip, Osteoporosis: New Paradigm. AB - Osteoporosis is the most common metabolic bone disease. Recently, the paradigm for diagnosis and treatment of osteoporosis has undergone changes due to new findings on this disease. With the arrival of densitometers that could measure BMD we started using medications that block further degradation of density and repair the densitometric results. More recent findings, however, suggest that the BMD value influences the predicted success of future fracture prevention in less than 50%. The remainder is attributed to bone quality. There are a number of risk factors for osteoporotic fractures, some of greater and some of lesser significance. A small external force is necessary to cause an osteoporotic fracture; otherwise, the osteoporotic bone still does not break. The dominant factor in a fracture is therefore the fall of the elderly patient. Falls are preventable, although most are benign and injury free. Only in the recent decade have we started paying attention to the fall phenomenon, which does not only involve accidents, but is also a consequence of the normal aging process. Incidence of falls and hip fractures in residential elderly patients can be reduced with a multifactorial interdisciplinary prevention program (MIPP):* Staff training * Adaptation of environment * Gait and mobility exercise * Technical accessories * Revision of pharmacotherapy (psychotropics) * Hip protectors * Post fall problem-solving conferences. Mobility exercise is useful in elderly groups; however, the maintenance of mobility is not linked to a reduction of fall risk. Hip protectors are protective pads designed to cover the greater trochanter and attenuate or disperse the force of fall sufficiently to prevent a hip fracture. A number of cost-benefit studies on residential elderly patients between 2004 and 2006 proved the efficacy of MIPP and hip protectors, and some studies did so also on those patients living independently. Unfortunately, as much as 75% of women and 90% ofmen at high risk in nursing homes are not investigated, and 75% of those affected are not treated. PMID- 26815624 TI - Iatrogenic Sciatic Nerve Palsy Following Hemiarthroplasty of the Hip. AB - We report a rare complication following insertion of an uncemented hip prosthesis that resulted in posterior perforation of the femoral stem and a sciatic nerve palsy. To our knowledge, sciatic nerve palsy due to the femoral stem perforating the cortex has not been previously described. PMID- 26815625 TI - Nonunion of a Pediatric Distal Radial Metaphyseal Fracture Following Open Reduction and Internal Fixation : A Case Report and Review of the Literature. AB - A boy, age 9, presented with deformation and pain of the left distal forearm, 1 year after a plate osteosynthesis for a distal radial metaphyseal fracture. This case showed a pediatric nonunion of a distal radial metaphyseal fracture which caused strong deformation of the left distal forearm. This is an extremely rare complication in children following an open reduction and internal fixation for a displaced distal forearm fracture. Key points of pediatric fracture healing are discussed and a review of the literature is given. PMID- 26815626 TI - Effective Hemostasis in Severe Mesenteric Vein Laceration with Tachosil((r)), using a Low- or Non-thrombogenic Patch to Prevent Tachosil((r))-induced Thrombosis. AB - Fibrinogen- and thrombin-coated collagen fleece (FTCC) facilitates surgical hemostasis, and is of particular value during resection of parenchymatous organs. Since thrombosis may ensue if the preparation is unintentionally applied intravascularly, it has not been recommended for treating lacerations of large veins, and no previous reports describe its use in vein repair. Our observations in two patients suggest, however, that FTCC might be indicated for hemostasis in vein injury where vascular suture is difficult or not possible, provided a low- or non-thrombogenic patch is interposed to prevent FTCC-induced vein thrombosis. Our two patients had severe lacerations of the proximal superior mesenteric vein (SMV) not amenable to conventional vein repair. Rapid hemostasis was obtained without suturing using Tachosil((r)), an FTCC preparation, covered with omentum. In the first patient hemostasis was obtained at the expense of vein thrombosis, apparently due to contact between the coagulant-containing side of Tachosil((r)) and the inside of the vein wall. In our second patient we therefore put a small patch of parietal peritoneum on the section of the Tachosil((r)) targeted to cover the vein tear to avoid direct contact between Tachosil((r)) and the vein lumen. Ultrasound examination 3 days postoperatively, and autopsy 11.5 months later showed that the vein was widely patent with no stenosis or thrombus. Our observations in these two patients were that an FTCC-omentum pack alone secured rapid hemostasis in severe SMV laceration, and when a peritoneal patch was interposed between FTCC and a lacerated SMV, FTCC-induced vein thrombosis did not occur. PMID- 26815627 TI - Bilateral Sacroiliac Joint Dislocation in an Adolescent after a Skiing Accident. AB - A bilateral sacroiliac joint (SI joint) dislocation is a rare injury pattern, in contrast to bilateral fracture dislocations of the SI joint. The incidence of pelvic dislocation of the SI joint without significant bone structural damage would most likely be observed in young children or adolescents after receiving a blunt, high energy impact. These young patients often suffer life threatening injuries to the intestines, neural or vascular systems or severe injury of the urinary tract. In these scenarios, plain projection radiographic imaging often leads to an inconclusive diagnosis making computer tomography indispensable to plan the treatment strategy. These strategies vary and the optimal approach is a subject to dispute. A surgical treatment of these injuries should ensure an immediate primary stability to allow early ambulation. The following study reports a unique trauma pattern with an isolated bilateral SI dislocation without fracture of the posterior or anterior pelvic ring nor concomitant injuries. This rare injury is a consequence of a pure vertical shear impact. This case report describes a technical pitfall of the iliolumbar transfixation and a solution to the problem. A dorso-ventro-dorsal approach, which utilizes both iliolumbar transfixation and ventral bilateral double plating osteosynthesis will be presented. PMID- 26815628 TI - Acute Traumatic Fibular Bowing Associated with Ankle Fracture. AB - We present a case of traumatic fibular bowing associated with ankle fracture in a 14-year-old girl. Acute traumatic bowing deformities of the fibula have always been reported as associated with mid-shaft tibial fractures, but involvement of the distal fibula associated with an ankle fracture has not been reported. The clinical picture is described and the mechanism of injury discussed. PMID- 26815629 TI - Abstracts : 27th Meeting of the Pediatric Section of the German Society of Trauma Surgeons (DGU), June 6-7, 2008 Mainz, Germany. PMID- 26815630 TI - Reduced lung function in smokers in a lung cancer screening cohort with asbestos exposure and pleural plaques. AB - BACKGROUND: While low dose computed tomography (LDCT) screening for lung cancer is recommended for high-risk smokers, ages 55-74 years, information about asbestos exposure may not be routinely elicited. Asbestos exposure is associated with declining respiratory function over time; however, the effect of a history of asbestos exposure in LDCT screening cohorts is limited. We report the relationship between asbestos exposure and pulmonary function in a cohort of heavy smokers with a history of occupational asbestos exposure, hypothesizing that these subjects will have additional decreased pulmonary function. We also examined relationships between spirometric measurements and the presence of isolated pleural plaques. METHODS: A cross-sectional study was performed using data from the NYU Lung Cancer Biomarker Center cohort to compare study subjects with a history asbestos exposure primarily in the period since 1970 when tighter federal standards were in place (n = 359) to those without asbestos exposure (n = 1038) with respect to pulmonary function, LDCT lung imaging findings, and clinical symptoms. We further classified individuals with asbestos exposure by length of exposure time to examine the effect of duration of exposure on pulmonary function. Lastly, for asbestos-exposed participants, we examined the association of spirometric measurements with the presence of absence of isolated pleural plaques. RESULTS: Individuals with asbestos exposure had decreased FVC % predicted compared to those with no asbestos exposure (76% vs. 85% predicted, P < 0.01) and FEV1 % predicted (64% vs. 67% predicted, P < 0.01). Since there was no change in FEV1 /FVC ratio, the findings are consistent with restrictive impairment. Those with >=20 years of exposure had a lower mean FVC % predicted compared to those with less than 20 years of exposure (74% vs. 78% predicted, P = 0.017). Individuals with asbestos exposure were more likely to have pleural plaques (P < 0.001) on CT. Those with isolated pleural plaques had lower mean % predicted FEV1 (P = 0.005) and FVC (P = 0.001) compared to those without pleural plaques. CONCLUSIONS: Occupational asbestos exposure in a cohort of heavy smokers was associated with a significant restrictive decline in pulmonary function, with longer duration of exposure associated with greater decline. The presence of isolated pleural plaques was also associated with reduced lung function. PMID- 26815631 TI - The role of 5-aminolevulinic acid in brain tumor surgery: a systematic review. AB - Recently, 5-aminolevulinic acid (5-ALA) has been utilized as an adjuvant to the surgical resection of primary brain tumors and metastases. We conducted a systematic review of the literature to further understand the role of 5-ALA in neurosurgery. Our goal was to identify the utility of 5-ALA during resection by evaluating its sensitivity and specificity for different tumor types, as well as the extent of tumor resection achieved while using 5-ALA. A search of the literature was conducted using the PubMed database for the period January 1990 through May 2014. Surgical series in which 5-ALA was used for brain neoplasm resections were evaluated for tumor histology, sensitivity, specificity, extent of resection, complications, and outcomes. Twenty-two series, involving 1163 patients, were included in our review. 5-ALA sensitivity was highest in high grade gliomas (85 %) and meningiomas (81 %). 5-ALA specificity was high in meningiomas (100 %), as well as metastases (84 %) and high-grade gliomas (82 %). Gross total resection (GTR) was achieved using 5-ALA in 66.2 % of all gliomas and 69.6 % of meningiomas, regardless of histological subtype. 5-ALA may be a useful tool in increasing the extent of resection and achieving GTR in intracranial tumors. The resection of tumors for which 5-ALA has high sensitivity and specificity, such as high-grade gliomas, may lead to an increase in extent of resection when compared to operations using only standard white light. Further evidence for the use of 5-ALA in meningiomas and certain subtypes of metastases may be needed to qualify its efficacy. PMID- 26815633 TI - Insights into structure and redox potential of lignin peroxidase from QM/MM calculations. AB - Redox potentials are computed for the active form (compound I) of lignin peroxidase (LiP) using a suitable QM/MM methodology (B3LYP/SDD/6 311G**//BP86/SVP:CHARMM). Allowing for dynamic conformational averaging, a potential of 0.67(33) V relative to ferrocenium/ferrocene is obtained for the active form with its oxoiron(iv) core. The computed redox potential is very sensitive to the charge distribution around the active site: protonation of titratable residues close to the metal center increases the redox potential, thereby rationalising the known pH dependence of LiP activity. A simple MM-charge deletion scheme is used to identify residues that are critical for the redox potential. Two mutant proteins are studied through homology modelling, E40Q and D183N, which are predicted to have an increased redox potential by 140 mV and 190 mV, respectively, relative to the wild type. These mutant proteins are thus promising targets for synthesis and further exploration toward a rational design of biocatalytic systems for oxidative degradation of lignin. PMID- 26815632 TI - Toll-like Receptor 7 Is Reduced in Severe Asthma and Linked to an Altered MicroRNA Profile. AB - RATIONALE: Asthma is one of the most common chronic diseases worldwide, and individuals with severe asthma experience recurrent exacerbations. Exacerbations are predominantly viral associated and have been linked to defective airway IFN responses. Ascertaining the molecular mechanisms underlying this deficiency is a major research goal to identify new therapeutic targets. OBJECTIVES: We investigated the hypothesis that reduced Toll-like receptor 7 (TLR7)-derived signaling drove the impaired IFN responses to rhinovirus by asthmatic alveolar macrophages (AMs); the molecular mechanisms underlying this deficiency were explored. METHODS: AMs were recovered from bronchoalveolar lavage from healthy subjects and patients with severe asthma. Expression of pattern-recognition receptors and microRNAs was evaluated by quantitative polymerase chain reaction and Western blotting. A TLR7-luciferase reporter construct was created to evaluate binding of microRNAs to the 3' untranslated region of TLR7. IFN production was measured by quantitative polymerase chain reaction and ELISA. MEASUREMENTS AND MAIN RESULTS: The expression of TLR7 was significantly reduced in severe asthma AMs and was associated with reduced rhinovirus and imiquimod induced IFN responses by these cells compared with healthy AMs. Severe asthma AMs also expressed increased levels of three microRNAs, which we showed were able to directly reduce TLR7 expression. Ex vivo knockdown of these microRNAs restored TLR7 expression with concomitant augmentation of virus-induced IFN production. CONCLUSIONS: In severe asthma, TLR7 deficiency drives impaired innate immune responses to virus by AMs. Blocking a group of microRNAs that are up-regulated in these cells can restore antiviral innate responses, providing a novel approach for therapy in asthma. PMID- 26815634 TI - A-thermal elastic behavior of silicate glasses. AB - Depending on the composition of silicate glasses, their elastic moduli can increase or decrease as function of the temperature. Studying the Brillouin frequency shift of these glasses versus temperature allows the a-thermal composition corresponding to an intermediate glass to be determined. In an intermediate glass, the elastic moduli are independent of the temperature over a large temperature range. For sodium alumino-silicate glasses, the a-thermal composition is close to the albite glass (NaAlSi3O8). The structural origin of this property is studied by in situ high temperature Raman scattering. The structure of the intermediate albite glass and of silica are compared at different temperatures between room temperature and 600 degrees C. When the temperature increases, it is shown that the high frequency shift of the main band at 440 cm(-1) in silica is a consequence of the cristobalite-like alpha-beta transformation of 6-membered rings. This effect is stronger in silica than bond elongation (anharmonic effects). As a consequence, the elastic moduli of silica increase as the temperature increases. In the albite glass, the substitution of 25% of Si(4+) ions by Al(3+) and Na(+) ions decreases the proportion of SiO2 6 membered rings responsible for the silica anomaly. The effects of the silica anomaly balance the anharmonicity in albite glass and give rise to an intermediate a-thermal glass. Different networks, formers or modifiers, can be added to produce different a-thermal glasses with useful mechanical or chemical properties. PMID- 26815635 TI - The biodistribution of the radiolabeled kinds of choline in male patients, assessed by PET/CT. PMID- 26815637 TI - Paraoxonase 1 Activity Is Modulated by the rs662 Polymorphism and IgG Anti-High Density Lipoprotein Antibodies in Patients With Rheumatoid Arthritis: Potential Implications for Cardiovascular Disease. AB - OBJECTIVE: Paraoxonase 1 (PON-1) is a high-density lipoprotein (HDL)-associated antioxidant enzyme that plays an important role in HDL-mediated cardioprotection. Although genetic polymorphisms are known to modulate PON-1 activity, its involvement in cardiovascular disease (CVD) in rheumatoid arthritis (RA) is controversial, suggesting that other factors may modulate its function. Since anti-HDL antibodies have been found to be related to an impaired lipid profile and occurrence of CVD in RA, this study was undertaken to examine the associations between PON-1 activity, anti-HDL antibodies, and CVD according to PON1 genetic variants in patients with RA. METHODS: Serum PON-1 activity, using paraoxon as substrate, and IgG anti-HDL antibodies were quantified in 212 RA patients and 110 healthy controls. The PON1 rs662 genotype (Q>R) was determined with TaqMan probes. An additional group of 13 biologics-naive patients with RA was prospectively followed up for 3 months. RESULTS: PON-1 activity was decreased in RA patients compared to healthy controls (P = 0.005), and an effect of the rs662 genotype was noted in both groups, with Q/Q homozygotes exhibiting the lowest PON-1 activity. The distribution of rs662 genotypes did not differ between RA patients and healthy controls (P = 0.215). In patients carrying the Q/Q genotype, anti-HDL antibodies were associated with impaired PON-1 activity (P = 0.010), and levels of anti-HDL antibodies were associated with decreased HDL levels (r = -0.680, P < 0.001) and higher prevalence of cardiovascular events, as determined in univariate and multivariate models. Furthermore, change in anti-HDL antibody levels upon tumor necrosis factor blockade was an independent predictor of improved PON-1 activity (beta = -0.369, 95% confidence interval -0.669, 0.069; P = 0.024). CONCLUSION: PON-1 activity is impaired in RA in association with the rs662 genotype and anti-HDL antibodies, the latter being recognized as a pivotal player in the link between rs662 and CVD in patients with RA. PMID- 26815638 TI - Challenges in interdisciplinary weight management in primary care: lessons learned from the 5As Team study. AB - Increasingly, research is directed at advancing methods to address obesity management in primary care. In this paper we describe the role of interdisciplinary collaboration, or lack thereof, in patient weight management within 12 teams in a large primary care network in Alberta, Canada. Qualitative data for the present analysis were derived from the 5As Team (5AsT) trial, a mixed-method randomized control trial of a 6-month participatory, team-based educational intervention aimed at improving the quality and quantity of obesity management encounters in primary care practice. Participants (n = 29) included in this analysis are healthcare providers supporting chronic disease management in 12 family practice clinics randomized to the intervention arm of the 5AsT trial including mental healthcare workers (n = 7), registered dietitians (n = 7), registered nurses or nurse practitioners (n = 15). Participants were part of a 6 month intervention consisting of 12 biweekly learning sessions aimed at increasing provider knowledge and confidence in addressing patient weight management. Qualitative methods included interviews, structured field notes and logs. Four common themes of importance in the ability of healthcare providers to address weight with patients within an interdisciplinary care team emerged, (i) Availability; (ii) Referrals; (iii) Role perception and (iv) Messaging. However, we find that what was key to our participants was not that these issues be uniformly agreed upon by all team members, but rather that communication and clinic relationships support their continued negotiation. Our study shows that firm clinic relationships and deliberate communication strategies are the foundation of interdisciplinary care in weight management. Furthermore, there is a clear need for shared messaging concerning obesity and its treatment between members of interdisciplinary teams. PMID- 26815640 TI - No evidence of genotype-3 hepatitis E virus-induced myocarditis. PMID- 26815641 TI - Delineating the Application of Ultrasound in Detecting Synovial Abnormalities of the Subtalar Joint in Juvenile Idiopathic Arthritis. AB - OBJECTIVE: To investigate the frequency of ultrasound (US)-detectable involvement of the subtalar joint (STJ), to compare clinical versus US assessment of the STJ, and to compare different scanning approaches to the STJ in juvenile idiopathic arthritis (JIA). METHODS: Clinical and US assessments were performed independently in 50 ankles with clinically active JIA. US abnormalities of the STJ were investigated using a lateral, medial, and posterior scanning approach and scored semiquantitatively. Agreement was tested using kappa statistics. A control group of 10 healthy subjects was examined. RESULTS: Clinical and US evaluations detected synovitis in 24 of 50 (48.0%) and 27 of 50 (54.0%) of STJs, respectively. US detected synovitis in 10 of 26 STJs (38.5%) recorded as normal on clinical evaluation, but was negative in 7 of 24 STJs (29.2%) diagnosed as having involvement on clinical examination. Agreement between clinical and US assessments was fair (kappa = 0.32). US abnormalities were more frequently detectable using the lateral scanning approach. All patients with US abnormalities in the medial and/or posterior side of the STJ had also US abnormalities on the lateral scanning approach, but the reverse was not true. Intra- and interobserver agreements for the lateral scanning approach were satisfactory for both detecting involvement and scoring US abnormalities. None of the 17 STJs of healthy controls showed US abnormalities. CONCLUSION: US may increase the precision of the evaluation of the STJ in JIA. The observed high frequency of STJ involvement on US suggests to include this joint in US scanning protocols devised for children with JIA. Synovitis is more frequently detected using the lateral scanning approach. PMID- 26815639 TI - ExoMeg1: a new exonuclease from metagenomic library. AB - DNA repair mechanisms are responsible for maintaining the integrity of DNA and are essential to life. However, our knowledge of DNA repair mechanisms is based on model organisms such as Escherichia coli, and little is known about free living and uncultured microorganisms. In this study, a functional screening was applied in a metagenomic library with the goal of discovering new genes involved in the maintenance of genomic integrity. One clone was identified and the sequence analysis showed an open reading frame homolog to a hypothetical protein annotated as a member of the Exo_Endo_Phos superfamily. This novel enzyme shows 3'-5' exonuclease activity on single and double strand DNA substrates and it is divalent metal-dependent, EDTA-sensitive and salt resistant. The clone carrying the hypothetical ORF was able to complement strains deficient in recombination or base excision repair, suggesting that the new enzyme may be acting on the repair of single strand breaks with 3' blockers, which are substrates for these repair pathways. Because this is the first report of an enzyme obtained from a metagenomic approach showing exonuclease activity, it was named ExoMeg1. The metagenomic approach has proved to be a useful tool for identifying new genes of uncultured microorganisms. PMID- 26815642 TI - Transplantation of activated nucleus pulposus cells after cryopreservation: efficacy study in a canine disc degeneration model. AB - Transplantation of activated nucleus pulposus (NP) cells obtained by coculturing NP cells and bone marrow mesenchymal stromal cells having cell-to-cell contact has been shown to be effective in animal models and, more recently, in human clinical trials. If the NP cells can be cryopreserved, then autologous cell transplantation could be offered to patients as and when required. In a previous study, we confirmed that activated NP cells can be obtained by coculturing with mesenchymal cells after cryopreservation. However, the in vivo effects of cell transplantation therapy using activated NP cells prepared from cryopreserved cells are not known. In this in vivo canine model, we compared indicators of disc degeneration in animals that received transplanted activated normal NP cells, transplanted cryopreserved NP cells, and no cell transplantation after induction of disc degeneration. The intervertebral disc height on radiographs and T2 weighted magnetic resonance imaging were significantly higher in both cell transplantation groups compared with the degenerated disc group. Macroscopic and histological findings demonstrated attenuated disc degeneration in the two transplanted groups. Intense staining of proteoglycan and collagen type II was seen in green fluorescent protein-labelled transplanted cells, which suggested that the cells had survived and were functioning after transplantation. No significant differences were observed between the two transplanted groups. Transplanted activated cryopreserved NP cells induced a similar attenuation of intervertebral disc degeneration as that of conventionally activated NP cells. These findings suggest that the use of cryopreserved cells specific to a patient's condition has potential in transplantation therapy. PMID- 26815643 TI - The response of tenocytes to commercial scaffolds used for rotator cuff repair. AB - Surgical repairs of rotator cuff tears have high re-tear rates and many scaffolds have been developed to augment the repair. Understanding the interaction between patients' cells and scaffolds is important for improving scaffold performance and tendon healing. In this in vitro study, we investigated the response of patient derived tenocytes to eight different scaffolds. Tested scaffolds included X Repair, Poly-Tape, LARS Ligament, BioFiber (synthetic scaffolds), BioFiber-CM (biosynthetic scaffold), GraftJacket, Permacol, and Conexa (biological scaffolds). Cell attachment, proliferation, gene expression, and morphology were assessed. After one day, more cells attached to synthetic scaffolds with dense, fine and aligned fibres (X-Repair and Poly-Tape). Despite low initial cell attachment, the human dermal scaffold (GraftJacket) promoted the greatest proliferation of cells over 13 days. Expression of collagen types I and III were upregulated in cells grown on non-cross-linked porcine dermis (Conexa). Interestingly, the ratio of collagen I to collagen III mRNA was lower on all dermal scaffolds compared to synthetic and biosynthetic scaffolds. These findings demonstrate significant differences in the response of patient-derived tendon cells to scaffolds that are routinely used for rotator cuff surgery. Synthetic scaffolds promoted increased cell adhesion and a tendon-like cellular phenotype, while biological scaffolds promoted cell proliferation and expression of collagen genes. However, no single scaffold was superior. Our results may help understand the way that patients' cells interact with scaffolds and guide the development of new scaffolds in the future. PMID- 26815644 TI - Electrochemical detection of Pseudomonas in wound exudate samples from patients with chronic wounds. AB - In clinical practice, point-of-care diagnostic testing has progressed rapidly in the last decade. For the field of wound care, there is a compelling need to develop rapid alternatives for bacterial identification in the clinical setting, where it generally takes over 24 hours to receive a positive identification. Even new molecular and biochemical identification methods require an initial incubation period of several hours to obtain a sufficient number of cells prior to performing the analysis. Here we report the use of an inexpensive, disposable electrochemical sensor to detect pyocyanin, a unique, redox-active quorum sensing molecule released by Pseudomonas aeruginosa, in wound fluid from patients with chronic wounds enrolled in the WE-HEAL Study. By measuring the metabolite excreted by the cells, this electrochemical detection strategy eliminates sample preparation, takes less than a minute to complete, and requires only 7.5 MUL of sample to complete the analysis. The electrochemical results were compared against 16S rRNA profiling using 454 pyrosequencing. Blind identification yielded 9 correct matches, 2 false negatives, and 3 false positives giving a sensitivity of 71% and specificity of 57% for detection of Pseudomonas. Ongoing enhancement and development of this approach with a view to develop a rapid point-of-care diagnostic tool is planned. PMID- 26815645 TI - Regulation of Anti-Mullerian Hormone and Its Receptor Expression around Follicle Deviation in Cattle. AB - The anti-Mullerian hormone (AMH) is an important marker of ovarian reserve and for predicting the response to superovulatory treatments in several species. The objective of this study was to investigate whether AMH and its receptor (AMHR2) are regulated in bovine granulosa cells during follicular development. In the first experiment, granulosa cells were retrieved from the two largest follicles on days 2 (before), 3 (at the expected time) or 4 (after deviation) of follicular wave. In the second experiment, four doses of FSH (30, 30, 20 and 20 mg) or saline were administered twice a day starting on Day 2 of the first follicular wave of the cycle. Granulosa cells and follicular fluid were collected from the two largest follicles 12 h after the last injection of FSH or saline. AMH mRNA abundance was similar in granulosa cells of the two largest follicles (F1 and F2) before deviation (Day 2), but greater in dominant (DF) than subordinate follicles (SF) at the expected time (Day 3) and after (Day 4) deviation (p < 0.05). In experiment 1, AMH mRNA levels declined in both DF and SF near the expected time and after deviation when compared to before deviation. There was no difference in AMHR2 mRNA levels before and during follicular deviation (p > 0.05), but they tended to be greater in DFs than SFs (p < 0.1) after deviation. Experiment 2 showed that AMH and AMHR2 mRNA in granulosa cells and AMH protein abundance in follicular fluid were similar (p > 0.05) between both co-dominant follicles collected from the FSH-treated cows. These findings indicate the followings: AMH mRNA levels decrease in both DFs and SFs during follicular deviation; granulosa cells from heathy follicles express more AMH mRNA compared to subordinate follicles undergoing atresia and FSH stimulates AMH and AMHR2 mRNA expression in granulosa cells of co-dominant follicles. PMID- 26815646 TI - The effect of embryo catheter loading technique on the live birth rate. AB - OBJECTIVE: Embryo loading (EL) is a major step in embryo transfer (ET) and affect on the success of in vitro fertilization (IVF). This study aimed to compare the effect of two different EL techniques on the rates of pregnancy and delivery in IVF/ET cycles. METHODS: 207 fresh ET and 194 Frozen-thawed ET (FET) cycles were included in this retrospective study. Two groups (A and B) were defined based on the EL technique used. In group A, the entire catheter was flushed with Ham's F 10 medium. The embryos were then drawn into the catheter using one air bracket. In group B, 70 uL of air was aspirated into the syringe and the catheter was flushed using Ham's F10 medium. The medium, air, embryos, air, and finally another layer of medium were then sequentially drawn into the catheter. The main outcome measures were the pregnancy and delivery rates. RESULTS: The groups did not differ with respect to the etiology of infertility, the source of spermatozoa, the quality of the embryos, the type of EL catheter, and the ease of transfer. The pregnancy rate was similar between two groups. In fresh ET cycles, a higher delivery rate was observed in group B than it group A (78.1% vs. 60%, p=0.1). In FET cycles, the rate of delivery was significantly higher in group B than in group A to a nonsignificant extent (88.9% vs. 58.8%, p=0.06). CONCLUSION: EL techniques did not have a significant impact on the delivery rate in either fresh or FET cycles. PMID- 26815647 TI - Factors in Deciding between Novel and Traditional Oral Anticoagulants to Prevent Embolism in Atrial Fibrillation Patients. PMID- 26815648 TI - Case 1/2016--Aortic Coarctation and Atrial Septal Defect submitted to Percutaneous Repair in Adult Patient. PMID- 26815649 TI - Middle Aortic Syndrome Treated by Implantation of an Advanta V12 Large Diameter Stent. PMID- 26815650 TI - Transcatheter Valve-in-Valve Repositioning of CoreValve(r) EvolutTM Rin Aortic Prosthesis. PMID- 26815651 TI - Paradigm-HF: a Paradigm Shift in Heart Failure Treatment? PMID- 26815652 TI - Donor-acceptor organo-imido polyoxometalates: high transparency, high activity redox-active NLO chromophores. AB - We show that polyoxometalates (POMs) are an excellent redox-active acceptor on which to base high performance 2(nd) order non-linear optical (NLO) chromophores. This is demonstrated through three new organoimido-Lindqvist derivatives with HRS beta0-values exceeding those of any dipolar organic system with comparable donor, pi-system and absorption profile. Thus, organoimido POMs may provide a new generation of high performance, high transparency, and potentially redox switchable NLO materials. PMID- 26815653 TI - Priority Questions and Horizon Scanning for Conservation: A Comparative Study. AB - Several projects aimed at identifying priority issues for conservation with high relevance to policy have recently been completed in several countries. Two major types of projects have been undertaken, aimed at identifying (i) policy-relevant questions most imperative to conservation and (ii) horizon scanning topics, defined as emerging issues that are expected to have substantial implications for biodiversity conservation and policy in the future. Here, we provide the first overview of the outcomes of biodiversity and conservation-oriented projects recently completed around the world using this framework. We also include the results of the first questions and horizon scanning project completed for a Mediterranean country. Overall, the outcomes of the different projects undertaken (at the global scale, in the UK, US, Canada, Switzerland and in Israel) were strongly correlated in terms of the proportion of questions and/or horizon scanning topics selected when comparing different topic areas. However, some major differences were found across regions. There was large variation among regions in the percentage of proactive (i.e. action and response oriented) versus descriptive (non-response oriented) priority questions and in the emphasis given to socio-political issues. Substantial differences were also found when comparing outcomes of priority questions versus horizon scanning projects undertaken for the same region. For example, issues related to climate change, human demography and marine ecosystems received higher priority as horizon scanning topics, while ecosystem services were more emphasized as current priority questions. We suggest that future initiatives aimed at identifying priority conservation questions and horizon scanning topics should allow simultaneous identification of both current and future priority issues, as presented here for the first time. We propose that further emphasis on social-political issues should be explicitly integrated into future related projects. PMID- 26815655 TI - The cognitive-emotional amalgam. AB - In the precis to The Cognitive-Emotional Brain, I summarize a framework for understanding the organization of cognition and emotion in the brain. Here, I address six major themes that emerged in the commentaries: (1) emotional perception and automaticity; (2) the status of cognition and emotion: together or separate? (3) evolutionary implications for the understanding of emotion and cognition; (4) the diverse forms of cognitive-emotional integration; (5) dual process theories; and (6) functional diversity of brain regions/networks and cognitive ontologies. The central argument is, again, that cognition and emotion are so highly interactive, and indeed integrated, that these two elements blend into a new amalgam. PMID- 26815656 TI - Correction: A Peptide Derived from the HIV-1 gp120 Coreceptor-Binding Region Promotes Formation of PAP248-286 Amyloid Fibrils to Enhance HIV-1 Infection. PMID- 26815658 TI - A versatile method for producing functionalized cellulose nanofibers and their application. AB - A facile method was developed to produce functionalized cellulose nanofibers in one step by ball milling. Through the synergy of mechanical and chemical actions, the produced cellulose nanofibers are ca. 20 nm wide and several micrometers long, with surface properties tailored by choice of modifying reagent. Modified by succinic anhydride, a cellulose nanofiber shows enhanced hydrophilicity, can be readily dispersed in water or DMSO, and gives a zeta potential of -38.7 mV due to carboxyl groups on the surface. Modified by dodecyl succinic anhydride, a cellulose nanofiber has excellent dispersibility in o-xylene and good compatibility with polyethylene. The polyethylene-cellulose nanofiber composite presents overall enhancement of mechanical properties. This method opens a new way to the production of functionalized cellulose nanofibers. PMID- 26815657 TI - Identification of Genes Relevant to Pesticides and Biology from Global Transcriptome Data of Monochamus alternatus Hope (Coleoptera: Cerambycidae) Larvae. AB - Monochamus alternatus Hope is the main vector in China of the Pine Wilt Disease caused by the pine wood nematode Bursaphelenchus xylophilus. Although chemical control is traditionally used to prevent pine wilt disease, new strategies based in biological control are promising ways for the management of the disease. However, there is no deep sequence analysis of Monochamus alternatus Hope that describes the transcriptome and no information is available about gene function of this insect vector. We used next generation sequencing technology to sequence the whole fourth instar larva transcriptome of Monochamus alternatus Hope and successfully built a Monochamus alternatus Hope transcriptome database. In total, 105,612 unigenes were assigned for Gene Ontology (GO) terms, information for 16,730 classified unigenes was obtained in the Clusters of Orthologous Groups (COGs) database, and 13,024 unigenes matched with 224 predicted pathways in the Kyoto Encyclopedia of Genes and Genome (KEGG). In addition, genes related to putative insecticide resistance-related genes, RNAi, the Bt receptor, intestinal digestive enzymes, possible future insect control targets and immune-related molecules are described. This study provides valuable basic information that can be used as a gateway to develop new molecular tools for Monochamus alternatus Hope control strategies. PMID- 26815660 TI - What is this chocolate milk in my circuit? A cause of acute clotting of a continuous renal replacement circuit: Questions. AB - INTRODUCTION: One of the greatest problems associated with continuous renal replacement therapy (CRRT) is the early clotting of filters. A literature search revealed three case reports of lipemic blood causing recurrent clotting and reduced CRRT circuit survival time in adult patients, but no reports of cases in children. DIAGNOSIS/TREATMENT: A 23-month-old male infant with Martinez-Frias syndrome and multivisceral transplant was admitted to the hospital with severe sepsis and hemolytic anemia. He developed acute kidney injury, fluid overload and electrolyte imbalances requiring CRRT and was also administered total parenteral nutrition (TPN) and fat emulsion. The first circuit lasted 60 h before routine change was required. The second circuit showed acute clotting after only 18 h, and brownish-milky fluid was found in the circuit tubing layered between the clotted blood. The patient's serum triglyceride levels were elevated at 988 mg/dL. The lipid infusion was stopped and CRRT restarted. Serum triglyceride levels improved to 363 mg/dL. The new circuit lasted 63 h before routine change was required. CONCLUSION: Clotting of CRRT circuits due to elevated triglyceride levels is rare and has not been reported in the pediatric population. Physicians should be mindful of this risk in patients receiving TPN who have unexpected clotting of CRRT circuits. PMID- 26815659 TI - A Novel, Noncanonical BMP Pathway Modulates Synapse Maturation at the Drosophila Neuromuscular Junction. AB - At the Drosophila NMJ, BMP signaling is critical for synapse growth and homeostasis. Signaling by the BMP7 homolog, Gbb, in motor neurons triggers a canonical pathway-which modulates transcription of BMP target genes, and a noncanonical pathway-which connects local BMP/BMP receptor complexes with the cytoskeleton. Here we describe a novel noncanonical BMP pathway characterized by the accumulation of the pathway effector, the phosphorylated Smad (pMad), at synaptic sites. Using genetic epistasis, histology, super resolution microscopy, and electrophysiology approaches we demonstrate that this novel pathway is genetically distinguishable from all other known BMP signaling cascades. This novel pathway does not require Gbb, but depends on presynaptic BMP receptors and specific postsynaptic glutamate receptor subtypes, the type-A receptors. Synaptic pMad is coordinated to BMP's role in the transcriptional control of target genes by shared pathway components, but it has no role in the regulation of NMJ growth. Instead, selective disruption of presynaptic pMad accumulation reduces the postsynaptic levels of type-A receptors, revealing a positive feedback loop which appears to function to stabilize active type-A receptors at synaptic sites. Thus, BMP pathway may monitor synapse activity then function to adjust synapse growth and maturation during development. PMID- 26815661 TI - Survivin and cycline D1 expressions are associated with malignant potential in mucinous ovarian neoplasms. AB - The most prevalent malignant ovarian neoplasms are epithelial ovarian cancers which is the most common cause of death among all gynecologic malignancies and a result of complex interaction of multiple oncogenes and tumor suppressor genes. The aim of this study was to evaluate expression of survivin and cycline D1 biomarkers in mucinous ovarian neoplasms and their correlations with clinicopathological variables in mucinous ovarian cancers. We analyzed pathological specimens of 98 patients with benign (n = 34), borderline (n = 22) and malignant (n = 42) mucinous ovarian neoplasms. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens. Immunohistochemical analysis revealed that survivin and cyclin D1 expressions were located primarily in the nucleus of ovarian tumor cells and relatively weaker cytoplasmic staining. Survivin expression was significantly higher in malignant tumors (88.1 %) than those found in borderline (18.2 %) and benign tumors (8.8 %) (p < 0.001). Similarly, higher cyclin D1 expression was observed in malignant tumors (100 %) compared to borderline (36.4 %) and benign tumors (5.9 %) (p < 0.001). Expression of all biomarkers analyzed significantly and gradually increased from benign to borderline and borderline to malignant mucinous tumors. In terms of clinicopathological variables, tumor grade, FIGO stage and lymph node methastasis were associated with the expression of both biomarkers. Whereas age exhibited no different correlations in mucinous ovarian cancers. The expressions of survivin and cycline D1 are positively correlated with the malignant potential of mucinous ovarian neoplasms. PMID- 26815662 TI - Silicon/Carbon Nanotube/BaTiO3 Nanocomposite Anode: Evidence for Enhanced Lithium Ion Mobility Induced by the Local Piezoelectric Potential. AB - We report on the synergetic effects of silicon (Si) and BaTiO3 (BTO) for applications as the anode of Li-ion batteries. The large expansion of Si during lithiation was exploited as an energy source via piezoelectric BTO nanoparticles. Si and BTO nanoparticles were dispersed in a matrix consisting of multiwalled carbon nanotubes (CNTs) using a high-energy ball-milling process. The mechanical stress resulting from the expansion of Si was transferred via the CNT matrix to the BTO, which can be poled, so that a piezoelectric potential is generated. We found that this local piezoelectric potential can improve the electrochemical performance of the Si/CNT/BTO nanocomposite anodes. Experimental measurements and simulation results support the increased mobility of Li-ions due to the local piezoelectric potential. PMID- 26815664 TI - Lateral Protein-Protein Interactions at Hydrophobic and Charged Surfaces as a Function of pH and Salt Concentration. AB - Surface adsorption of Thermomyces lanuginosus lipase (TLL)-a widely used industrial biocatalyst-is studied experimentally and theoretically at different pH and salt concentrations. The maximum achievable surface coverage on a hydrophobic surface occurs around the protein isoelectric point and adsorption is reduced when either increasing or decreasing pH, indicating that electrostatic protein-protein interactions in the adsorbed layer play an important role. Using Metropolis Monte Carlo (MC) simulations, where proteins are coarse grained to the amino acid level, we estimate the protein isoelectric point in the vicinity of charged surfaces as well as the lateral osmotic pressure in the adsorbed monolayer. Good agreement with available experimental data is achieved and we further make predictions of the protein orientation at hydrophobic and charged surfaces. Finally, we present a perturbation theory for predicting shifts in the protein isoelectric point due to close proximity to charged surfaces. Although this approximate model requires only single protein properties (mean charge and its variance), excellent agreement is found with MC simulations. PMID- 26815663 TI - Etiological Influences on Perceptions of Parenting: A Longitudinal, Multi Informant Twin Study. AB - Children and their parents often differ in their perception of the relationship they share. As this relationship changes developmentally, the nature of these differences may also change. Longitudinal genetic designs can be used to investigate the developmental etiologies of shared and distinct perceptions. In this study, we used longitudinal psychometric models to analyze child and parent reports of negative parenting for 6417 twin pairs from the Twins Early Development Study at ages 9, 12 and 14 years. Within-time cross-reporter correlations, indicating the degree to which children and parents perceived negative parenting behaviors similarly at each age, were moderate (r = .44 - .46). Longitudinal genetic analyses revealed these shared perceptions to be relatively stable during the transition into adolescence, with this stability driven by a combination of children's genetic factors and family-wide environmental factors. In contrast, child- and parent-specific perceptions of parenting were predominantly age-specific, a developmental pattern underpinned by child genetic factors and a combination of family-wide and unique environmental influences. These results and their implications are discussed in the context of interplay between reciprocal interactions, subjective insight and developmental behavioral change in the parent-child relationship. PMID- 26815665 TI - Trauma registries in Europe. PMID- 26815666 TI - Epidemiology of in-hospital trauma deaths. AB - PURPOSE: About half of all trauma-related deaths occur after hospital admission. The present study tries to characterize trauma deaths according to the time of death, and, thereby, contributes to the discussion about factors considered as the cause of death. METHODS: Data from two large European trauma registries (Trauma Registry of the German Society of Trauma Surgery, TR-DGU, and the Trauma Audit and Research Network, TARN) were analyzed in parallel. All hospital deaths with Injury Severity Score (ISS) > 9 documented between 2000 and 2010 were considered. Patients were categorized into five subgroups according to the time to death (0-6 h; 7-24 h; day 1-6; day 7-30; beyond day 30). Surviving patients from the same time period served as a control group. RESULTS: In total, 6,685 and 6,867 non-survivors were included from the TR-DGU and TARN, respectively. The hospital mortality rate was between 15 and 17%. About half of all deaths occurred within the first 24 h after admission (TR-DGU: 54%; TARN: 45%). The earliest subgroup of trauma deaths showed the highest mean ISS and the highest rate of mass transfusions. Severe head injury was most frequently observed in the subgroup of day 1-6. Late deaths are associated with higher age and more complications (sepsis, multiple organ failure). CONCLUSIONS: The time to death after severe trauma does not follow a trimodal distribution but shows a constantly decreasing incidence. PMID- 26815667 TI - Regionalisation of trauma care in Germany: the "TraumaNetwork DGU((r))-Project". AB - PURPOSE: The care for severely injured patients is a demanding task for all medical professionals involved in both the pre-clinical and the clinical setting. While the overall quality of care in Germany is high, regional differences remain. These are due to geographical and infrastructural variations, as well as different personnel and equipment situations in the hospitals. METHODS: In September 2006, the white paper 'Treatment of the severely injured' was published by the German Society of Trauma Surgery (DGU). The white paper asks for the improvement of comprehensive care and postulates the foundation of networks between trauma centres: a regional TraumaNetwork (TNW). All hospitals within a TNW are classified as local, regional or supraregional trauma centres by distinct criteria regarding personnel and equipment, as well as admission capacity and responsibility. Furthermore, agreements between the trauma centres and the pre hospital rescue systems regulate the admission and transfer of patients in a TNW. RESULTS: To date, 878 hospitals are registered in 53 regional TNWs. A total of 511 hospitals have already been audited on-site. Preparing for the audit, 54.4% of the hospitals implemented organisational changes (e.g. inter-disciplinary guidelines), while 31.4% introduced personnel and 14.7% structural (e.g. X-ray in the emergency room [ER]) changes. In September 2011, the certification process was completed in 19 TNWs, comprising a mean of 14 (range 5-26) hospitals each. Moreover, international TNWs in co-operation with hospitals in Holland, Luxemburg, Switzerland and Austria were established. CONCLUSIONS: The TraumaNetwork DGU((r)) audits all hospitals participating in the care for severely injured patients and establishes a structured network between all the players involved in trauma care. Thirty TNWs will be certified by the end of 2011, covering 75% of Germany. The nationwide covering will be completed by the middle of 2012. PMID- 26815668 TI - Multiple blunt trauma after suicidal attempt: an analysis of 4,754 multiple severely injured patients. AB - PURPOSE: The suicidal attempt is a significant cause for multiple severe injuries in Germany. The aim of the present study was to obtain information regarding injury patterns, clinical treatment, and outcome. METHODS: We analyzed the data of 4,754 patients of the Trauma Registry of the German Trauma Society (1993-2007) with an Injury Severity Score (ISS) >=9 after a suicidal jump from a height (SUICIDE) and after an accidental fall from a height (ACCIDENT). RESULTS: Comparing the data of 3,682 patients with accidental fall versus those with intentional fall/jump (n = 1,072), we found that male patients were predominant in the ACCIDENT group (84.9 vs. 52.2%). The SUICIDE group had more severe injuries (ISS: 31.8 vs. 26.4). The ACCIDENT group suffered more severe head injuries (51.1 vs. 36.6%). Mortality (21.4 vs. 14.2%), length of stay in hospital (29.5 vs. 26.5 days), and costs (?34,833 vs. ?24,701) were higher in the SUICIDE group. CONCLUSIONS: Falls from a height are a common cause of injury among severely injured patients. The resulting trauma composes a particular form of blunt trauma with severe and multiple injuries, which depends on the fact of whether the free fall from a height was caused by an accident or as a result of a suicidal attempt. Taking the injury severity into consideration, there is no difference in the prognosis of the patients. PMID- 26815669 TI - Prognostic value of various intracranial pathologies in traumatic brain injury. AB - OBJECTIVE: Various intracranial pathologies in traumatic brain injury (TBI) can help to predict patient outcomes. These pathologies can be categorised using the Marshall Classification or the Abbreviated Injury Scale (AIS) dictionary or can be described through traditional descriptive terms such as subarachnoid haemorrhage (SAH), subdural haemorrhage (SDH), epidural haemorrhage (EDH) etc. The purpose of this study is to assess the prognostic value of AIS scores, the Marshall Classification and various intracranial pathologies in TBI. METHODS: A dataset of 802 TBI patients in the Trauma Audit and Research Network (TARN) database was analysed using logistic regression. First, a baseline model was constructed with age, Glasgow Coma Scale (GCS), pupillary reactivity, cause of injury and presence/absence of extracranial injury as predictors and survival at discharge as the outcome. Subsequently, AIS score, the Marshall Classification and various intracranial pathologies such as haemorrhage, SAH or brain swelling were added in order to assess the relative predictive strength of each variable and also to assess the improvement in the performance of the model. RESULTS: Various AIS scores or Marshal classes did not appear to significantly affect the outcome. Among traditional descriptive terms, only brain stem injury and brain swelling significantly influenced outcome [odds ratios for survival: 0.17 (95% confidence interval [CI]; 0.08-0.40) and 0.48 (95% CI; 0.29-0.80), respectively]. Neither haemorrhage nor its subtypes, such as SAH, SDH and EDH, were significantly associated with outcome. Adding AIS scores, the Marshall Classification and various intracranial pathologies to the prognostic models resulted in an almost equal increase in the predictive performance of the baseline model. CONCLUSIONS: In this relatively recent dataset, each of the brain injury classification systems enhanced equally the performance of an early mortality prediction model in traumatic brain injury patients. The significant effect of brain swelling and brain stem injury on the outcome in comparison to injuries such as SAH suggests the need to improve therapeutic approaches to patients who have sustained these injuries. PMID- 26815670 TI - Evidence for improved outcome following use of hemostatic fibrin sealants in HPB surgery? AB - INTRODUCTION: The development of fibrin sealants has been progressing; they are now often applied as fibrinogen-coated collagen patches. MATERIALS AND METHODS: The concept has been increasingly applied in hepato-pancreato-biliary surgery, for example, following liver resection, and to some extent also in pancreatic surgery, both in order to reinforce the pancreatic anastomosis at pancreaticoduodenectomy and to seal the pancreatic stump following distal pancreatectomy. CONCLUSION: High quality evidence in the form of major prospective, randomized clinical studies is still lacking on in the field of HPB. There is also an the absence of proper cost-utility analyses. PMID- 26815671 TI - Ultrasonographic evaluation of costal cartilage fractures unnoticed by the conventional radiographic study and multidetector computed tomography. AB - INTRODUCTION: Rib fractures are the most common injuries resulting from blunt chest trauma. However, costal cartilage fractures are almost invisible on chest X rays unless they involve calcified cartilage. The sensitivity of conventional radiography and computed tomography for detecting rib fractures is limited, especially in cases where rib cartilage is involved. Therefore, this study was designed to evaluate the sensitivities of chest wall ultrasonography, clinical findings, and radiography in the detection of costal cartilage fractures. MATERIALS AND METHODS: A total of 93 patients presenting with a high clinical suspicion of rib or sternal fractures were recruited for radiological workup with posterior-anterior (PA) chest radiographs, oblique rib views, sternal views, computed tomography, and chest ultrasound between April 2008 and May 2010. There were 47 men and 46 women, and the mean age of the patients was 51.8 +/- 15.9 years (range 17-78 years). These patients with minor blunt chest trauma showed no evidence of rib fractures on conventional radiography and computed tomography, and no evidence of other major fractures. Chondral rib fractures were detected by using ultrasonography on a 7.5-MHz linear transducer. RESULTS: Of the total 93 patients, 64 (68.8%) showed chondral rib fractures, whereas 29 (31.2%) did not. The mean number of chondral rib fracture sites detected in 64 patients was 1.8 +/ 0.8 (range 1-5). Subperiosteal hematoma was the most common finding associated with costal cartilage fractures (n = 14, 15.0%), followed by sternal fracture (n = 9, 9.7%). However, subperiosteal hematoma was also noticed in 1 (1.1%) of the patients without costal cartilage fractures, and sternal fractures in 7 patients (7.5%). DISCUSSION: The results of this study suggest that ultrasonography may be a useful imaging method for detecting costal cartilage fractures overlooked on conventional radiographs and computed tomography in patients with minor blunt chest trauma. Early ultrasonographic evaluation can give more accurate information than clinical and radiologic evaluation in detecting costal cartilage fractures and sternal fractures that are overlooked on conventional radiography and computed tomography after minor blunt chest trauma. PMID- 26815672 TI - Gastrointestinal tract perforation following blunt abdominal trauma: an institution's experience. AB - PURPOSE: Traumatic perforation of the gastrointestinal tract (GIT) poses numerous challenges for surgeons worldwide. We aimed to review our institution's experience and highlight the pertinent issues in managing this problem. METHODS: A retrospective review was performed for all patients with perforation of the GIT following traumatic blunt injuries. RESULTS: Twenty-one patients, with a median age of 40 years, formed the study group, all of whom underwent surgery. Four patients were sent straight to the operating theater from the emergency department due to hemodynamic instability, while another two patients had pneumoperitoneum on their X-rays. Computed tomography (CT) scan was performed in 15 patients, with the findings of pneumoperitoneum (n = 7, 46.7%) and free fluid without solid organ injury (n = 9, 60.0%) being the most common result. The jejunum (n = 11, 52.4%) and ileum (n = 5, 23.8%) were the most common sites of perforation. Direct repair was performed in 9 (42.9%) patients, while resection of the perforated segment(s) was performed in the remaining 12 (57.1%) patients. Other associated intra-abdominal injuries included mesenteric (n = 6, 28.6%) and splenic lacerations (n = 4, 19.0%). Surgery was performed within 8 h of the accident in only 11 patients (52.4%). Some of the complications included wound infection (n = 7, 33.3%) and intra-abdominal abscesses (n = 3, 14.3%). Two patients underwent relook laparotomy after an initial damage control laparotomy. CONCLUSION: Prompt and early surgery for traumatic gastrointestinal perforation is advised. Any abnormal CT scans warrants either surgery or close monitoring. Direct repair of the perforation is preferred, if possible. PMID- 26815673 TI - Hip fracture surgery and performance indicators: an analysis of 941 patients operated in a large teaching hospital. AB - BACKGROUND: In the Netherlands, two performance indicators for the treatment of hip fracture patients have been recently implemented. Both indicators state that surgery within 24 h after admission improves the outcome with regard to 1-year mortality and the amount of re-operations within 1 year. To determine the value of these performance indicators, we conducted a retrospective analysis of 941 hip fracture patients. METHODS: In the period from January 2003 to December 2006, a total of 941 consecutive hip fracture patients were included in this study. We determined the amount of re-operations and the mortality at 1 year after surgery. From June 2005 to December 2006, we could determine whether patients were operated on within 24 h after admission. In this group of 379 patients, we determined if there were differences in the 1-year mortality and the number of re operations at 1 year with regard to the time window in which these patients were operated on (<24 h or >24 h). RESULTS: Our overall mortality rate at 1 year is 21% (202 patients) and the amount of re-operations within 1 year is 8% (77 procedures). In our subgroup analysis, we found no significant difference in mortality or re-operations if patients were operated on within 24 h or not (number needed to treat of 59 and -31, respectively). CONCLUSION: We conclude that hip fracture surgery within 24 h does not provide significantly better results in terms of 1-year mortality and the amount of re-operations within 1 year. PMID- 26815674 TI - Biomechanical comparison of two locking plate systems for the distal tibia. AB - BACKGROUND: Distal tibia fractures are known to be difficult to stabilize and nonunions often occur because of a relative instability of the fragments. Therefore, it was of interest to ascertain how different locking plates behave regarding stiffness and interfragmentary movement in comminuted distal tibia fractures. METHODS: A locked medial plate (AxSOS) for the medial distal tibia and a locked medial plate (LCP) for the distal medial tibia were compared biomechanically under compression and torsional load. The tibiae were osteotomized in distal intersection between 4/5 and 5/5, with a gap of 10 mm after instrumentation. For compression force, a load of 350 N was applied and for torsion, a torque of 0-10 Nm and back to 0 over -5-Nm intervals was performed. Stiffness was calculated from the machine data and interfragmentary movement was measured with an optoelectronic measurement device. RESULTS: Under compression load, the stiffness showed no significant differences between the AxSOS plate compared to the LCP. Significant differences were seen in the interfragmentary movement, where the LCP showed 1.03 mm compared to 0.6 mm for the AxSOS plate. In torsional testing, the AxSOS plate showed significantly higher stiffness than the LCP. The AxSOS plate and the LCP showed similar values for interfragmentary movement under torsional load. CONCLUSION: The treatment of distal tibia fractures with angle-stable medial AxSOS plate showed less interfragmentary movement and higher stiffness than fracture fixation with a locked medial LCP. Even if there are no significant differences in torsional testing, plating of the distal tibia should be performed with a steel plate from the biomechanical view. PMID- 26815675 TI - Pediatric fractures: temporal trends and cost implications of treatment under general anesthesia. AB - PURPOSE: Pediatric fractures are common and are often managed by manipulation under general anesthesia (MUA). This study's aim was to assess the changing pattern of pediatric fractures over 6 years and use this data to perform a workload forecast and estimate cost implications of treatment under general anesthesia. METHODS: The Emergency Department (ED), operating theater and ward admissions data of children aged 1-11 years presenting with fractures was analyzed. We calculated caseload trends, delay to operation, various parameters of service provision, and the current cost of treating each fracture. We then performed predictive cost analysis for the next 3 years to estimate potential savings by manipulating fractures in ED under ketamine sedation. RESULTS: The case load has increased >350% in 6 years (total fractures increasing at 23% and MUAs increasing at 17% per year, respectively). The summer months and evenings have been consistently busier. 72% of fractures were managed by pure reduction alone (MUA), 22% by reduction + K-wires, and various other procedures were performed in 1%. The median delays from ED presentation to admission, definitive procedure and discharge were 4, 21 and 33 h, respectively. Each MUA took 52 min and cost the hospital L723. Assuming that the current trends continue, the expenditures would be L101 K, L114 K, and L128 K for 2010, 2011 and 2012, respectively. DISCUSSION: Fracture manipulation in children under general anesthesia often requires an overnight hospital stay, which is not only uncomfortable for the child and inconvenient for the parents but it also increases the burden on the limited National Health Service (NHS) resources. There is a 23% annual increase in fractures and children have to wait for 21 h before the definitive procedure. Using ketamine to manipulate children's fractures in the ED could offer potential service and cost improvements. PMID- 26815677 TI - Optic nerve sheath measurement and raised intracranial pressure in paediatric traumatic brain injury. AB - INTRODUCTION: The optimal management of children ventilated for more than 4 h with traumatic brain injury (TBI) necessitates invasive intracranial pressure (ICP) monitoring, though some patients never have raised ICP. If non-invasive screening can reliably rule out elevated ICP, invasive devices can be limited to those in whom neuro-intensive care measures are indicated. MATERIALS AND METHODS: We measured the optic nerve sheath diameter (ONSD) with a 10-MHz ultrasound probe in 11 children (age range 2-15 years, median 9.2 years) with severe TBI admitted to a regional neuro-surgical paediatric intensive care unit (PICU) requiring ICP monitoring and neuro-protection. Simultaneous invasive ICP was recorded and more than 15 mmHg was considered to be abnormal. ONSD >4.5 mm in children over 1 year of age was considered to be abnormal. RESULTS AND CONCLUSIONS: All children with clinically significantly raised ICP had abnormal ONSD, whereas those with normal ICP did not. Despite the small numbers, this study suggests that the ONSD may be useful in identifying children with TBI and normal ICP and, so, help avoid the insertion of unnecessary ICP monitors. PMID- 26815676 TI - Evaluating the effects of immediate application of negative pressure therapy after decompression from abdominal compartment syndrome in an experimental porcine model. AB - PURPOSE: The purpose of this large-animal study was to assess the safety and effects of negative pressure therapy (NPT) when used as temporary abdominal closure in the immediate post-decompression period after abdominal compartment syndrome (ACS). METHODS: Using a hemorrhagic shock/resuscitation and mesenteric venous pressure elevation model, ACS was physiologically induced in 12 female Yorkshire swine. At decompression, animals were allocated to either NPT (n = 6) or Bogota bag (n = 6) as temporary abdominal closure and studied for a period of 48 h or until death. Outcomes measured included morbidity and mortality, as well as hemodynamic parameters, ventilator-related measurements, blood gases, coagulation factors, and organ (liver, kidney, lung, and intestinal) edema and histology at the time of death/sacrifice. RESULTS: All animals developed ACS. Early application of NPT was associated with decreases in mesenteric venous and central venous pressure, and significantly increased drainage of peritoneal fluid. In addition, there was no increase in the incidence of mortality, recurrent intra-abdominal hypertension/ACS, or any deleterious effects on markers of organ injury. CONCLUSIONS: Early application of NPT in this porcine ACS model is safe and does not appear to be associated with an increased risk of recurrent intra-abdominal hypertension. The results of this animal study suggest that the application of NPT following decompression from ACS results in greater peritoneal fluid removal and may translate into augmented intestinal edema resolution secondary to more favorable fluid flux profiles. PMID- 26815678 TI - Open to laparoscopic conversion in hemoperitoneum of unknown origin. AB - PURPOSE: Demonstrating the potential, in spite of the current trend, of closing an open emergency surgical procedure and to convert it to a minimally invasive approach. METHODS: Case report of an open converted to a laparoscopic approach in an emergency setting for hemoperitoneum of unknown origin. RESULTS: A 28-year-old female patient was transported to the operating room for suspected acute appendicitis. Through McBurney's incision, hemoperitoneum was found. She was hemodynamically stable. The open incision was closed and a laparoscopic approach established. The diagnosis was a ruptured right ectopic pregnancy with mild hemoperitoneum. After a laparoscopic salpingectomy, her recovery was uneventful. CONCLUSIONS: For selected cases, the conversion of an open procedure to a laparoscopic approach offers a real benefit for the patient, avoiding a large laparotomy and its associated morbidity. PMID- 26815680 TI - Which Future for Traumatology in Europe? PMID- 26815679 TI - Lack of alpha2C-Adrenoceptor Results in Contrasting Phenotypes of Long Bones and Vertebra and Prevents the Thyrotoxicosis-Induced Osteopenia. AB - A series of studies have demonstrated that activation of the sympathetic nervous system (SNS) causes osteopenia via beta2-adrenoceptor (beta2-AR) signaling. However, in a recent study, we found an unexpected and generalized phenotype of high bone mass in female mice with chronic sympathetic hyperactivity, due to double gene inactivation of adrenoceptors that negatively regulate norepinephrine release, alpha2A-and alpha2C-AR (alpha2A/2C-AR-/-). These findings suggest that beta2-AR is not the single adrenoceptor involved in bone turnover regulation and show that alpha2-AR signaling may also mediate the SNS actions in the skeleton. In addition, we found that alpha2A/2C-AR-/- animals are resistant to the thyrotoxicosis-induced osteopenia, suggesting that thyroid hormone (TH), when in supraphysiological levels, interacts with the SNS to control bone mass and structure, and that this interaction may also involve alpha2-AR signaling. In the present study, to further investigate these hypotheses and to discriminate the roles of alpha2-AR subtypes, we have evaluated the bone phenotype of mice with the single gene inactivation of alpha2C-AR subtype, which mRNA expression was previously shown to be down regulated by triiodothyronine (T3). A cohort of 30 day-old female alpha2CAR-/- mice and their wild-type (WT) controls were treated with a supraphysiological dose of T3 for 30 or 90 days, which induced a thyrotoxic state in both mouse lineages. The micro-computed tomographic (MUCT) analysis showed that alpha2C-AR-/- mice present lower trabecular bone volume (BV/TV) and number (Tb.N), and increased trabecular separation (Tb.Sp) in the femur compared with WT mice; which was accompanied by decreased bone strength (determined by the three-point bending test) in the femur and tibia. The opposite was observed in the vertebra, where alpha2C-AR-/- mice show increased BV/TV, Tb.N and trabecular thickness (Tb.Th), and decreased Tb.Sp, compared with WT animals. In spite of the contrasting bone phenotypes of the femur and L5, thyrotoxicosis negatively regulated most of the micro architectural features of the trabecular bone in both skeletal sites of WT, but not of alpha2C-AR-/- mice. T3 treatment also decreased biomechanical properties (maximum load and ultimate load) in the femur and tibia of WT, but not of knockout mice. The mRNA expression of osteocalcin, a marker of mature osteoblasts, and tartrate-resistant acid phosphatase, which is expressed by osteoclasts and is involved in collagen degradation, was increased by T3 treatment only in WT, and not in alpha2C-AR-/- mice. Altogether, these findings suggest that alpha2C-AR subtype mediates the effects of the SNS in the bone in a skeletal site-dependent manner, and that thyrotoxicosis depends on alpha2C-AR signaling to promote bone loss, which sustains the hypothesis of a TH-SNS interaction to modulate bone remodeling and structure. PMID- 26815681 TI - Focus on Severe Pelvic Bleeding. PMID- 26815682 TI - Management of Acute Hemorrhage in Pelvic Trauma: An Overview. AB - Pelvic disruption is a combination of fractures or dislocations of the pelvic ring with trauma of the soft tissues on the inside and outside of this ring. Hemodynamic instability is the result of blood loss out of the fracture fragments, the posterior venous plexus, ruptured pelvic organs, or arterial lesions. In the resuscitation phase, different measures are possible to reduce the volume of the disrupted pelvis and to restore mechanical stability. They are not competitive but complementary. Pelvic binders should be used in the prehospital phase before and during transport. Application of a pelvic C-clamp is restricted to inhospital patients with C-type pelvic ring lesions and with severe and ongoing hemodynamic instability. External fixation is most useful in B-type but also has limited value in C-type injuries. The prerequisite for pelvic packing is the restoration of mechanical stability by pelvic C-clamping or external fixation. It is effective in severe venous bleeding in the small pelvis. Pelvic angiography and selective embolization is performed in patients with active arterial bleeding. These patients can be identified by a convincing clinical picture, by early multislice computed tomography (CT) with contrast- enhanced angiographic technique, or by the persistent need for volume replacement after C-clamping, external fixation, or pelvic packing. PMID- 26815683 TI - Today's Role of External Fixation in Unstable and Complex Pelvic Fractures. AB - INTRODUCTION: The treatment of pelvic fractures has undergone a change over the past few years. As there seems to be a trend away from external towards internal fixation, the goal of this study was to investigate whether the use of an external fixator is still a standard procedure for the initial as well as - if necessary - for the definitive treatment of complex and unstable pelvic injuries. METHODS: During a period of five years at the Level I Trauma Center, an external fixator was applied in 28 (11%) out of 236 pelvic ring fracture cases. The common indications were open fractures, complex fractures and multiple injuries with hemodynamic instability. Hemorrhage control, fracture stabilization and infection prophylaxis in cases of open fracture were achieved by variable placement and fixation of Schanz screws. In some cases, the assembly of a hybrid combined with internal osteosynthesis was used to increase stability. RESULTS: Of the 28 patients, 20 survived, while eight (28.6%) died in the course of treatment due to fatal hemorrhage, craniocerebral trauma, multi-organ failure and sepsis. A satisfactory result (anatomical and functional outcome) was achieved in 16 of the 20 cases (80%). The remaining four (20%) suffered from serious complications, the majority of them caused by the initial type of injury. CONCLUSIONS: The use of the external fixator for the initial and in some cases for the definitive fixation of unstable and complex pelvic injuries with hemodynamic instability is still a successful treatment of multiply injured patients. PMID- 26815684 TI - Severe Pelvic Bleeding: The Role of Primary Internal Fixation. AB - Pelvic ring injuries form part of the spectrum of polytraumaandmust be considered a potentially lethal injury with mortality rates of 10-20%. The stabilization of the unstable pelvic ring in acute resuscitation of multiply injured patients is now conventional wisdom.We aimed: (1) to design a new iliosacral (IS) screw, (2) to prove the clinical advantages of this new implant, and (3) to work out the optimal surgical strategy using this implant. Taking the demands of the above mentioned data into account, a 10 mm 2.8 mm-cannulated iliosacral screw seemed to be optimal for the special requirements. Before industrial production, finite element analysis (FEA) was performed to find out whether these screws would be enough to stabilize the posterior pelvic ring alone or not. Clinical experience led to the modification of the set of instruments, which finally yielded handy tools and implants. Building further on the surgical skills and experiences gained (by the surgeons and the O.R. personnel), we increased our capacity to perform more and more immediate pelvic fixations. Emergency pelvic stabilizationswere performed in patientswith pelvic injuries who had hemodynamic instability, despite immediate shockmanagement during the diagnostic period. During thelast eleven years, 244 patientswith Tile B3 and Cpelvic injuries have been stabilized with 10-mm diameter cannulated IS screws percutaneously posteriorly. Fortyeight hemodynamically unstable patientswere stabilized in the first 2 h with iliosacral screw fixation. The percutaneous pelvic ring stabilization with 10-mm cannulated screws provedstrongenoughin bothersome casesaswell. PMID- 26815685 TI - Pelvic Fractures: Soft Tissue Trauma. AB - Severe open injuries of the pelvis go with a high complication, morbidity and mortality rate. A stepwise approach is the way to achieve reasonable results; however, final clinical outcome is in a large number of cases suboptimal. PMID- 26815686 TI - Outcome in Pelvic Ring Fractures. AB - Pelvic ring fractures represent a negative prognostic factor for what concerns morbidity and mortality of a polytraumatized patient. The subjective and functional prognosis of a pelvic ring fracture is dependent upon its degree of instability. Associated severe peripelvic soft tissue injuries and neurovascular lesions (complex pelvic trauma) affect outcome negatively. Although high rates of anatomic reduction and stable fixation have been achieved in recent years, only 60% of patients have an excellent or good clinical result. Sequelae of neurologic lesions and genitorurinary injuries are typically associated with considerable rates of persistent functional impairment. Chronic pain and disability are often very difficult to treat. Health-related quality of life and life satisfaction after pelvic ring fractures caused by high-energy trauma is substantially lower when compared to a reference population. PMID- 26815687 TI - Pelvic Fracture and Risk Factors for Mortality: A Population-Based Study in Taiwan. AB - OBJECTIVE: To study the incidence, demographics, distribution of fracture sites, associated injuries, and risk factors for the outcomes of pelvic fracture on a population basis. METHODS: An annual claim dataset from 2001 to 2003 was retrieved from the Bureau of National Health Insurance (BNHI) trauma database with any International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) coded as pelvic fracture. Statistical analyses were conducted to discover the association between variables such as age, gender, month of injury, injury mechanisms, associated injuries, and outcome. RESULTS: Pelvic fracture was diagnosed in 10,109 patients (4,693 males, 46.4%) and 384 patients (3.8%) died. The incidence was 14.97/100,000 person-years. The mean length of stay was 9.3 days (females, 8.8 days; males, 9.9 days; p < 0.01) and the average cost per patient was US$1,475. Both were affected by age, gender, and hospital accreditation level and ownership. There were more female cases in the age groups over 44 years old. Head injury (excluding concussion), associated chest and abdominal injuries, open pelvic fracture, and the transfusion of more than four units of blood significantly increased the risk of mortality. CONCLUSIONS: The incidence rate of pelvic fracture was higher in females over 44 years of age, but the average medical resource use was higher in males. Associated injuries were stronger positive factors for the risk of mortality than gender, fracture sites, injury mechanisms, and the characteristics of the treating hospitals. PMID- 26815688 TI - The Role of Ultrasound in Penetrating Trauma. AB - A dramatic reduction of penetrating trauma is not to be expected in the near future, especially in some regions of the world. In order to identify the body structures damaged after stab or firearm wounds, complementary diagnostic studies play an essential role in assessing the severity of the case. The inclusion of ultrasound among the diagnostic tests for assessing abdominal injuries after blunt trauma because of its confident, repetitive, non-invasive, communicable, and low-cost means to obtain the relevant information is derived from rapidly widespread use of the method for other injury mechanisms, such as penetrating trauma. The excellent results in sensitivity and specificity obtained by ultrasound in the search of free fluid among patients with blunt trauma have pushed emergency physicians to try a similar implementation in the penetrating trauma setting. Ultrasonography enables experienced examiners to obtain diagnostic details from the injured patient. Regarding free fluid, it is possible to determine its presence and composition through the peritoneal aspiration after a sonoguided puncture. On the other hand, ultrasound is able to detect morphologic changes in solid organs after penetrating trauma. In order to reach these possibilities which are offered by the ultrasound technology, a planifying training and education program must be developed. PMID- 26815689 TI - Perforated Duodenal Ulcer: Has Anything Changed? AB - INTRODUCTION: To assess the current management and outcome of perforated duodenal peptic ulcer managed with open repair, a focused analysis was conducted, excluding gastric, traumatic and iatrogenic perforations. PATIENTS AND METHODS: A retrospective study of a 6-year period identified 61 patients. Mean age was 59 (range 19-87) years and 33 (54%) were male. Medical history included nonsteroidal anti-inflammatory drugs in 46%, smoking in 30%, atherosclerosis in 26% and excessive alcohol use in 23%. RESULTS: Generalized abdominal tenderness was recorded in 64% of the cases. The mean (SD) C-reactive protein value was 100 (141) g/l and white blood cell count was 12.8 (7.9) E9/l. Plain abdominal X-ray was positive for air in 87% (41/47) and CT scan in 86% (18/21). Four patients (7%) were operated without radiological imaging. There were 31 patients (51%) with a delay of 24 h or more from the start of symptoms to surgery. The mean (SD) delay from admission to surgery was 9 (3) (range 3-12) h. The treatment consisted of open suture repair in 92%, peritoneal lavage in 92%, external drainage in 80% and nasogastric decompression in 92%. The overall hospital mortality and morbidity rates were 11 and 21%, respectively. The duodenal suture leak rate was 7% and intra-abdominal abscess rate was 2%. CONCLUSION: The majority of patients with perforated duodenal ulcer can be diagnosed with conventional clinical and radiological methods, and treated according to established surgical principles. The mortality and duodenal morbidity rates have remained unchanged for the last decade. Shortening preoperative delay could improve the prognosis. PMID- 26815690 TI - Computer-assisted Femur Fracture Reduction. AB - INTRODUCTION: When using intramedullary nailing of femur fractures false axis alignment or malrotation is the greatest deterrent to successful reduction often causing extended x-ray exposure and the need to revert to an open procedure. The aim of this study was to demonstrate the advantages of using a trauma navigation system during intramedullary nailing of femur fractures. MATERIALS AND METHODS: A fluoroscopic navigation unit was used and successful closed fracture reduction, x ray exposure, and operation time were measured. Between 2004 and 2007 19 patients receiving intramedullary nailing of femur fractures using a Stryker trauma navigation system were included in the study. The results were compared to 10 conventionally operated femur fractures between 2003 and 2006. RESULTS: The study demonstrated an important reduction of radiation time and less needs for reverting to open reduction. CONCLUSION: Based on these findings we conclude that the use of a trauma navigation system during fracture reduction has clear advantages. These are based primarily on its ability to provide 3-dimensional viewing of the fracture during the reduction procedure. This eliminates the need for multiple positioning adjustments of the x-ray C-arm from horizontal to vertical for better viewing and in doing so reduced radiation time and needs for open reduction. PMID- 26815691 TI - Epidemiology of Fatal Trauma in Italy in 2002 Using Population-Based Registries. AB - BACKGROUND: Population-based registries have been proposed for epidemiologic studies and quality assessment in trauma care because they consider the entire population of a given geographic area. PATIENTS AND METHODS: Trauma mortality in pre-hospital and in-hospital settings and death time from injury have been calculated for Italy during 2002 by cross-analyzing two national databases: the death certificates register (DCD) and the hospital discharge register (HDR). All diagnosis codes from 800.0 to 939.9 and from 950.0 to 959.9 in both the DCD and the HDR, with the exclusion of femur fractures (820.0 and 821.9) if older than 65, have been included. RESULTS: The total number of people who died during 2002 as a consequence of trauma in Italy was 15,456; of these, 43.5% were older than age 64, and 35.9% belonged to the 15-44 age group. The overall incidence rate of trauma death was 27.23 per 100,000 inhabitants/ year, with a relative risk to men vs. women of 2.3. An analysis of the time distribution of the trauma deaths showed that 46.8% were pre-hospital mortalities, 18% of the deaths occurred within 48 h after hospital admission (acute mortality), 11.2% of the deaths occurred between three and seven days after admission (early mortality), and 24.0% of the patients died more than seven days after admission (late mortality). Patients who died before they arrived at hospital were younger and the proportion of men was higher than for the deaths that occurred after hospital arrival. CONCLUSION: The use of population-based registries proved to be effective in our study because it allowed us to use currently available data to obtain information useful for trauma system planning and design. PMID- 26815692 TI - A Prospective Study of Blunt Abdominal Trauma at the University of Calabar Teaching Hospital, Nigeria. AB - BACKGROUND: Blunt abdominal trauma (BAT) usually results from motor vehicle accidents, assaults, and recreational accidents or falls. This communication is a 3-year report of an ongoing study aimed at providing the current BAT prevalence in our center. It is hoped that this would assist in a better design of prevention and emergency trauma response systems to cope with this epidemic. METHODS: All of the patients admitted to the University of Calabar Teaching Hospital (UCTH), Calabar, Nigeria, from February 2005 to January 2008 were prospectively studied based on a questionnaire. Hemodynamic stability and sonography formed the basis for selecting patients for non-operative management (NOM); others were offered laparotomy. RESULTS: In total, 4,391 emergencies were seen during the study period, of which 1,654 (38%) were due to trauma. Seventy nine patients with abdominal trauma accounted for 4.8% of trauma cases. Forty-two (53%) patients suffered BAT and their ages ranged from 14 and 56 years (mean 28.4 years), with a male:female ratio of 2.5:1. Road traffic accidents accounted for 13 (87%) and 26 (96%) patients in the NOM and laparotomy groups, respectively. The most commonly injured organ was the spleen in both groups: 8 (50%) and 15 (56%) in the NOM and laparotomy groups, respectively. Fifteen (36%) patients were managed successfully in the NOM group. CONCLUSION: Trauma was mainly due to road traffic injuries. Hemodynamic stability and ultrasonography effectively selected patients for NOM. The establishment of trauma systems, provision of ancillary diagnostic and monitoring facilities, well-designed roads and traffic infrastructure, and health education on road safety would reduce injury, morbidity, and mortality. PMID- 26815693 TI - Spinal Fusion of an Unstable Atlantoaxial Fracture in a Completely Tetraplegic Patient Using Silicate-Substituted Calcium Phosphate. AB - Bone graft harvesting from the iliac crest constitutes the gold standard in spinal surgery due to its osteogenic, osteoconductive and osteoinductive properties. Large amounts of autograft can provoke complications like donor site morbidity, pain and the need for a second operation. Therefore, research into bone graft substitutes is of great interest. Silicate-substituted calcium phosphate (Actifuse(TM) Synthetic Bone Graft, ApaTech Ltd, London) was used in combination with morselized corticocancellous graft in a transarticular stabilization (modified Magerl) of a completely tetraplegic patient with an unstable atlantoaxial fracture. Computed tomography showed bone bridging between the segment C1/C2, the surface of the implant and the remodeled bone at follow-up at 8 months. The use of silicate-substituted calcium phosphate as a bone graft extender in spinal surgery could be an alternative to autografting from the iliac crest. Vegetative symptoms are often underestimated but can be triggered by donor site morbidity or pain in patients after spinal cord injury. PMID- 26815694 TI - Retrieval of Recovery IVC Filter After 1,463-Day Implantation. AB - A young female victim of multiple trauma had a Recovery inferior vena cava filter placed for pulmonary embolism prophylaxis. She was lost to follow-up for planned retrieval of the filter. After a period of more than four years she re-presented and had successful and uneventful retrieval of the filter. Certain inferior vena cava filters may potentially be retrieved even after very long implantation periods. PMID- 26815695 TI - Scarf-Related Hangman's Fracture: A Case Report. AB - BACKGROUND: Injury to the cervical spine due to a scarfassociated accident has not been reported in the literature. We present a case of a hangman's fracture in a 43-year-old woman that resulted from a scarfrelated injury as a consequence of a motor vehicle accident. PURPOSE: To identify the mechanism of a scarf-related injury causing Hangman's fracture. CASE REPORT: A 43-year-old woman was involved in a motor vehicle accident. She was wearing a scarf, which is a common clothing accessory for women in Malaysia. The scarf was violently torn off her head during the injury, causing a type I hangman's fracture. A halo vest for a total period of 3 months was applied. CONCLUSION: A scarf-related injury can cause an injury that resembles judicial hanging, leading to a traumatic spondylolisthesis of the axis. Careful evaluation of the cervical spine radiographs is crucial as occult fracture of the axis can be missed. PMID- 26815696 TI - Large Osteochondral Fracture in a Patient with Bilateral Bicondylar Osteochondritis Dissecans and Spondyloepiphyseal Dysplasia Tarda. AB - We report a case of a large osteochondral fracture in a patient with bicondylar, bilateral osteochondritis dissecans and spondyloepiphyseal dysplasia tarda. PMID- 26815697 TI - Intracranial internal carotid artery dissection following waterslide use: the first case report. PMID- 26815698 TI - Langerhans cell histiocytosis with seborrheic eczema of the scalp and extensive calvarial involvement. AB - INTRODUCTION: Langerhans cell histiocytosis (LCH) is a multisystem disorder of unknown etiology and characterized by accumulation of histiocytes in various tissues. CASE REPORT: A 3-year-old, previously healthy girl presented with progressive flattening of the parietal convexity for 6 months and seborrheic eczema of the scalp. At presentation, the patient showed no neurological deficit. The eczemas were extensively distributed over the scalp, but not found in any other site of the body. Blood examination revealed a marked increase in soluble interleukin-2 receptor levels. Neuroimages revealed multiple calvarial defects that were replaced by well-demarcated, enhancing extracerebral masses. A biopsy surgery confirmed the diagnosis as LCH. CONCLUSION: LCH may cause progressive calvarial defects. If seborrheic eczemas are concurrent, they may suggest prompt histological verification and treatments be initiated. PMID- 26815699 TI - The fa2 gene and molecular markers mapping in the gp segment of the Pisum linkage group V. AB - Review studies on the world Pisum genetic resources have shown that stem fasciation is controlled by three loci, i.e., fa1 (LGIV; Wt 10006 - type line of the Polish Gene Bank), fa2 (LGV, the line Wt 12185), and fas (LGIII, the line Shtambovii). Outstanding advantages of this character (e.g., pods gathered in upper part of a stem) resulted in breeding some cultivars. Preliminary investigations suggested linkages of the newly described fa2 gene within the gp-U segment. Based on the further linkage test crosses, it was stated that the fa2 is localized between the gp and Pis_Gen_9_3_1 markers (in the LGV). Additionally, four molecular markers (AD175, AB146, AC58, and AD280) and the morphological marker lk were also localized in this segment. Moreover, rms5, lum3, and cri were found to map on the other side of gp with tight linkage observed between lum3 and cri. PMID- 26815700 TI - Emergence of Multiplex Communities in Collaboration Networks. AB - Community structures in collaboration networks reflect the natural tendency of individuals to organize their work in groups in order to better achieve common goals. In most of the cases, individuals exploit their connections to introduce themselves to new areas of interests, giving rise to multifaceted collaborations which span different fields. In this paper, we analyse collaborations in science and among movie actors as multiplex networks, where the layers represent respectively research topics and movie genres, and we show that communities indeed coexist and overlap at the different layers of such systems. We then propose a model to grow multiplex networks based on two mechanisms of intra and inter-layer triadic closure which mimic the real processes by which collaborations evolve. We show that our model is able to explain the multiplex community structure observed empirically, and we infer the strength of the two underlying social mechanisms from real-world systems. Being also able to correctly reproduce the values of intra-layer and inter-layer assortativity correlations, the model contributes to a better understanding of the principles driving the evolution of social networks. PMID- 26815701 TI - Evidence vs advocacy in the e-cigarette debate: to vape or not to vape, that is the question. PMID- 26815702 TI - Blood eosinophils: the Holy Grail for asthma phenotyping? PMID- 26815703 TI - Gut microbiota and allergic disease in children. PMID- 26815704 TI - Asthma, oculonasal symptoms, and skin test sensitivity across National Health and Nutrition Examination Surveys. AB - BACKGROUND: The increasing prevalence of allergies and asthma has been reported. However, the progression of the prevalence of allergy (the "allergic diathesis progression") has not been examined over time from skin test positivity to oculonasal symptoms to the development of asthma. OBJECTIVE: To investigate the change in the prevalences and associations of positive skin test reactions, oculonasal symptoms, and asthma during the Second and Third National Health and Nutrition Examination Surveys (NHANES II and NHANES III, respectively). METHODS: Data collected during NHANES II and III were used. The prevalence and associations of positive skin test reactions, oculonasal symptoms, and asthma and the linear trend of oculonasal symptoms and asthma prevalence across different cumulative positive skin test reactions were calculated for each NHANES period. RESULTS: From NHANES II to NHANES III, the prevalence of asthma doubled (2 times) and increased for positive skin test reactions (2.2 times), oculonasal symptoms (3.3 times), and concurrence of asthma, oculonasal symptoms, and positive skin test reactions (5.3 times). People were sensitive to an increasing number of allergens. Positive skin test reactions increased from 0.2% (NHANES II) to 2.7% (NHANES III) for people allergic to all 6 allergens. CONCLUSION: Despite some methodologic differences in skin tests across NHANES II and III, this study demonstrated significant increases in allergen sensitivities (prevalence and number of allergens), oculonasal symptoms, and asthma over a 20-year course, indicating that increased sensitivity led to increased allergic symptoms and asthma during the 20 years from NHANES II to NHANES III. PMID- 26815705 TI - Influences of asthma on reported health indicators and access to health care among children. AB - BACKGROUND: Studies on the influences of pediatric asthma on health and access to health care were conducted in limited geographic areas or age groups. OBJECTIVE: To investigate associations of asthma with health, use of medical care, mental health or educational services, activity limitations, problems in paying bills, and frustrations in obtaining health care among children in the United States. Caregivers reported children's conditions. METHODS: Logistic regression models were adjusted for sociodemographic factors in the nationally representative 2011/2012 National Survey of Children's Health. RESULTS: Of the 91,116 children 0 to 17 years old, 14.6% had reported asthma. Of children 0 to 17 years old with asthma, 21.2% were non-Hispanic black. Of children 0 to 17 years old without asthma, 12.2% were non-Hispanic black. In children 0 to 17 years old, compared with children without asthma, children with asthma had an increased odds to have reported fair or poor health, receive more medical care, mental health, and educational services than usual, have activity limitations, have medical bills that the family had problems paying (odds ratio 1.5, 95% confidence interval 1.3 1.7), and have caregivers who were frustrated in obtaining care (odds ratio 1.5, 95% confidence interval 1.2-1.7). The odds ratios for the associations between asthma and all outcomes were higher in the 0- to 5-year-old compared with the 6- to 17-year-old group. CONCLUSION: When adjusting for sociodemographic variables, caregivers have problems paying bills and obtaining health care services for their child. To develop age-appropriate interventions, more research is needed to understand why families have difficulties accessing health care. PMID- 26815706 TI - Intrapartum antibiotic exposure for group B Streptococcus treatment did not increase penicillin allergy in children. AB - BACKGROUND: Group B Streptococcus (GBS) is the leading infectious cause of neonatal morbidity and mortality in the United States. Intrapartum administration of antibiotics to mothers with positivity to GBS is performed for prevention, with penicillin being the drug of choice. Previous studies have noted an increase in atopic diseases other than drug allergy associated with intrapartum antibiotic exposure. OBJECTIVE: To determine whether intrapartum exposure to penicillin for GBS increases the likelihood of penicillin allergy in children. METHODS: Retrospective chart review was performed for patients from a birth cohort. The birth cohort included children born in 2007 at a tertiary care hospital and had local addresses. Information on GBS status of the mother, intrapartum antibiotic exposure, delivery mode, and birth order was collected and analyzed. RESULTS: Of 927 children identified, 804 were included in the cohort. Eighty children (10%) had a reported penicillin allergy; most were white (79%) and boys (61%). Intrapartum exposure to penicillin (odds ratio 0.84, 95% confidence interval 0.45 1.57, P = .59) or to amoxicillin or ampicillin (odds ratio 0.22, 95% confidence interval 0.01-3.71, P = .29) did not increase the risk of penicillin allergy in children. In addition, all other factors evaluated did not affect the risk of penicillin allergy in children. CONCLUSION: To the authors' knowledge, this is the first study to evaluate intrapartum exposure to penicillin for GBS treatment and subsequent development of penicillin allergy in the child. In contrast to other atopic diseases, intrapartum antibiotic exposure does not alter the risk of penicillin allergy. Parents and obstetricians should be reassured when using penicillin for prevention of neonatal GBS. PMID- 26815707 TI - High prevalence of Anisakis simplex hypersensitivity and allergy in Sicily, Italy. AB - BACKGROUND: Anisakis simplex can elicit allergic reactions when ingested in raw or marinated fish. The prevalence of A simplex hypersensitivity and allergy in Sicily (Italy), an area where the consumption of raw or marinated fish is very common, has not been investigated thus far. OBJECTIVE: To investigate the prevalence of A simplex sensitization and its clinical relevance in a large group of unselected patients. METHODS: All consecutive patients referred to the authors' allergy clinic during a 22 month-period were included in the study, evaluated for sensitization to A simplex and other allergens depending on their clinical history, and investigated for allergic symptoms after the ingestion of raw or marinated fish. RESULTS: Of 3,419 patients screened, 527 (15.4%) were sensitized to A simplex and 29 of these (5.5% of sensitized patients) had a history of A simplex allergy. Approximately 30% of patients had mono sensitization to A simplex. Co-sensitization to house dust mites or molds yielded an odds ratio of 1.98 or 3.18, respectively, for allergy to A simplex. CONCLUSION: A high prevalence of A simplex sensitization in a large proportion of patients with mono-sensitization was found, confirming that eating habits influence sensitization to this nematode. Allergic symptoms from A simplex ingestion in raw or marinated fish were quite frequent, with symptoms ranging from oral allergy syndrome to anaphylaxis. Patients sensitized to A simplex were more prone to have allergic symptoms when they had co-sensitization to house dust mites or molds, suggesting possible cross-reactive but clinically relevant allergens between these allergenic sources. PMID- 26815708 TI - How effective are the 6 European Society of Immunodeficiency warning signs for primary immunodeficiency disease? AB - BACKGROUND: The European Society of Immunodeficiency (ESID) developed 6 warning signs to promote the awareness of adult primary immunodeficiency disease (PID). OBJECTIVE: To screen adult patients for the presence of PID using these 6 warning signs to determine the effectiveness of this protocol. METHODS: Questions related to the ESID warning signs for adult PID were added to the standard outpatient clinic file system and asked of 3,510 patients who were admitted to our clinic for any reason. Patients with signs and/or suspicion of PID based on their medical history underwent immunologic investigation. RESULTS: In total, 24 patients were diagnosed as having a PID. The most common reason that patients with PID were admitted was frequent infection (n=18 [75%]), and the most common PID subgroup was common variable immunodeficiency (n=12 [50%]). Twenty patients with PID had at least one positive finding according to the ESID warning signs. Two patients with gastrointestinal concerns and 2 with dermatologic symptoms were also diagnosed as having a PID, although they did not have any of the ESID warning signs. CONCLUSION: The ESID warning signs do not specify the need for symptoms to diagnose a PIDs and do not include a comprehensive list of all signs and symptoms of PIDs. As a result, more than infection-centric questions are needed to identify adult patients with immunodeficiencies. PMID- 26815709 TI - Pre-seasonal, subcutaneous immunotherapy: a double-blinded, placebo-controlled study in elderly patients with an allergy to grass. AB - BACKGROUND: There is limited evidence indicating that specific immunotherapy in elderly patients is safe and effective. OBJECTIVE: To evaluate the safety and efficacy of pre-seasonal specific subcutaneous immunotherapy (SCIT) against grass pollen allergens in patients older than 65 years with seasonal allergic rhinitis and to measure the prime outcome of area under the curve for the combined symptoms and medication score during grass pollen season after 3 years of SCIT in a double-blinded, placebo-controlled trial. METHODS: This study included 60 65- to 75-year-old patients with seasonal allergic rhinitis and grass pollen allergy. Patients were individually randomized to the active or placebo group. Thirty three subjects in the SCIT group and 27 subjects in the placebo group were monitored for 3 years. Patients were required to record each use of anti-allergy medication. RESULTS: Thirty-one patients completed 3 years of pre-seasonal SCIT and 24 subjects finished placebo treatment. The median area under the curve for the combined symptoms and medication score after the third grass pollen season after SCIT was significantly decreased from 7.85 (range 3.67-8.98) to 4.63 (range 3.56-7.80) in the active group and did not significantly change in the placebo group. In the active group, the combined symptoms and medication score was decreased by 41%, the symptoms score was decreased by 55%, and the medication score was decreased by 64% after 3 years of immunotherapy. CONCLUSION: Pre seasonal SCIT in the elderly is safe and efficacious and elicits an immune response comparable to what is found in studies of younger patients. PMID- 26815710 TI - How many systemic reactions to skin prick tests could be preventable in defined conditions? PMID- 26815711 TI - A Colorado allergist's experience with marijuana legalization. PMID- 26815712 TI - Author response. PMID- 26815713 TI - Classification of angioedema without wheals. PMID- 26815714 TI - [Not Available]. PMID- 26815715 TI - [Not Available]. PMID- 26815716 TI - [New promising treatments of Ebola virus disease are underway]. AB - The largest Ebola epidemic ever is about to end. No major breakthrough in terms of specific treatment has been seen, but a number of valuable lessons have been learned, including the potential of intensive supportive care. New products are under development, but clinical trials were initiated late in the epidemic leading to inability to include sufficient numbers. Several large vaccine trials are underway with one vaccine so far showing 100 per cent efficacy. A paradigm shift in accelerated testing of drugs and vaccines during an ongoing epidemic is emerging. PMID- 26815717 TI - [Not Available]. PMID- 26815718 TI - [Bunk rails and children can be a dangerous cocktail]. AB - We present a case with a two-year-old girl, who accidentally got caught between a mattress and a metal rod used as rail of an upper bunk and almost got suffocated. To rule out child abuse and to clarify the sequence of events, the incident was reported to the police. The police investigation and the forensic examination confirmed the incident as reported by the parents and the police closed the case. With this case story, we want to warn against the use of rails, with a distance between mattress and rail allowing the body of a small child to slip under and trap a proportionally bigger head. PMID- 26815719 TI - [Transvaginal hybrid natural orifice transluminal endoscopic surgery cholecystectomy]. AB - Natural orifice transluminal endoscopic surgery (NOTES) is a minimally invasive surgical technique where access to the abdominal cavity is achieved through one of the natural orifices of the body. Based on experience from gynaecology, transvaginal access has been the easiest NOTES technique to implement in clinical practice. As was the case with laparoscopy, transvaginal NOTES has primarily been evaluated for cholecystectomy. Although the evidence is limited, the data support a safety profile comparable to that of laparoscopy. As for potential benefits, further research needs to be conducted. PMID- 26815720 TI - [A pseudopapillary tumour in the parametrium]. AB - This is a case report of a 48-year-old woman with a history of unexplained abdominal pain. She was admitted with a clinical presentation consistent with ovarian torsion. A CT-scan showed a 9 cm large tumour, which was interpreted as an ovarian cyst on the left side with bleeding and possible torsion. Acute laparoscopy was converted to laparotomy. Multiple excrescences and a solid tumour in the left parametrium were found consistent with solid pseudopapillary neoplasia. Due to the rarity of this condition the patient was referred to a specialized surgical department. PMID- 26815721 TI - [Popliteal venous aneurysm]. AB - Popliteal venous aneurysm is a rare disease. The diameter of the vein is at least twice as big as the normal proximal vein. The aneurysm is usually asymptomatic but it can suddenly cause pulmonary embolism even in young persons. Due to an unpredictable risk of thromboembolism even under anticoagulation treatment operation is often advisable if the diameter of the aneurysm is more than 20 mm. The operation can usually be done as tangential aneurysmectomy and lateral venorrhaphy which has a low complication rate and a good patency. PMID- 26815722 TI - Increased ratio of peritoneal effusion-to-serum potassium concentration in a dog with gastric perforation. AB - OBJECTIVE: To describe the clinical and laboratory findings of a dog with gastric perforation, resulting in a markedly increased peritoneal effusion-to-serum potassium ratio. CASE SUMMARY: A 6-year-old mixed breed neutered male dog presented with a right femoral fracture after being hit by car. The fracture was repaired surgically. Four days postoperatively, the dog developed peritoneal effusion, confirmed with ultrasonography. Peritoneal effusion analysis and serum biochemistry, performed concurrently, showed blood-to-effusion glucose difference >1.1 mmol/L [>20 mg/dL], suggesting the effusion was septic. The effusion-to serum creatinine ratio was mildly increased (1.36) and the effusion-to-serum potassium ratio was markedly increased (>2.67). Combined, these findings were suggestive of a septic uroabdomen. A positive contrast retrograde urethrocystography did not reveal urine leakage from the lower urinary tract. An exploratory laparotomy revealed a gastric perforation in the pyloric area and an intact urinary tract. NEW INFORMATION PROVIDED: Gastric perforation should be considered a differential diagnosis in dogs with an increased peritoneal effusion to serum potassium ratio. PMID- 26815723 TI - Sunitinib activates Axl signaling in renal cell cancer. AB - Mass spectrometry-based phosphoproteomics provides a unique unbiased approach to evaluate signaling network in cancer cells. The tyrosine kinase inhibitor sunitinib is registered as treatment for patients with renal cell cancer (RCC). We investigated the effect of sunitinib on tyrosine phosphorylation in RCC tumor cells to get more insight in its mechanism of action and thereby to find potential leads for combination treatment strategies. Sunitinib inhibitory concentrations of proliferation (IC50) of 786-O, 769-p and A498 RCC cells were determined by MTT-assays. Global tyrosine phosphorylation was measured by LC MS/MS after immunoprecipitation with the antiphosphotyrosine antibody p-TYR-100. Phosphoproteomic profiling of 786-O cells yielded 1519 phosphopeptides, corresponding to 675 unique proteins including 57 different phosphorylated protein kinases. Compared to control, incubation with sunitinib at its IC50 of 2 uM resulted in downregulation of 86 phosphopeptides including CDK5, DYRK3, DYRK4, G6PD, PKM and LDH-A, while 94 phosphopeptides including Axl, FAK, EPHA2 and p38alpha were upregulated. Axl- (y702), FAK- (y576) and p38alpha (y182) upregulation was confirmed by Western Blot in 786-O and A498 cells. Subsequent proliferation assays revealed that inhibition of Axl with a small molecule inhibitor (R428) sensitized 786-O RCC cells and immortalized endothelial cells to sunitinib up to 3 fold. In conclusion, incubation with sunitinib of RCC cells causes significant upregulation of multiple phosphopeptides including Axl. Simultaneous inhibition of Axl improves the antitumor activity of sunitinib. We envision that evaluation of phosphoproteomic changes by TKI treatment enables identification of new targets for combination treatment strategies. PMID- 26815724 TI - Using the Reliability Theory for Assessing the Decision Confidence Probability for Comparative Life Cycle Assessments. AB - Comparative decision making process is widely used to identify which option (system, product, service, etc.) has smaller environmental footprints and for providing recommendations that help stakeholders take future decisions. However, the uncertainty problem complicates the comparison and the decision making. Probability-based decision support in LCA is a way to help stakeholders in their decision-making process. It calculates the decision confidence probability which expresses the probability of a option to have a smaller environmental impact than the one of another option. Here we apply the reliability theory to approximate the decision confidence probability. We compare the traditional Monte Carlo method with a reliability method called FORM method. The Monte Carlo method needs high computational time to calculate the decision confidence probability. The FORM method enables us to approximate the decision confidence probability with fewer simulations than the Monte Carlo method by approximating the response surface. Moreover, the FORM method calculates the associated importance factors that correspond to a sensitivity analysis in relation to the probability. The importance factors allow stakeholders to determine which factors influence their decision. Our results clearly show that the reliability method provides additional useful information to stakeholders as well as it reduces the computational time. PMID- 26815725 TI - Disparate Response to Methotrexate in Stem Versus Non-Stem Cells. AB - Methotrexate (MTX) is a commonly used chemotherapeutic agent that kills cancer cells by binding dihydrofolate reductase (DHFR) as a competitive inhibitor. Due to its non-selectivity, MTX also impairs normal (non-cancerous) cell function and causes long-term damage to healthy tissue. These consequences have been investigated extensively in bone-derived cells due to their sensitivity to the drug. While DHFR likely plays a role in normal cell response to MTX, research in this area is limited. Moreover, how MTX sensitivity differs among cell types responsible for maintaining connective tissues is unknown. The goal of this study was to investigate the role of DHFR and subsequent nucleotide synthesis in normal cell response to MTX. We also sought to compare adverse effects of MTX among normal cell types to identify sensitive populations and resistant cell sources for regenerative procedures targeting patients undergoing chemotherapy. DHFR overexpression or exogenous amino acid + nucleoside delivery rescued normal cells from adverse MTX effects. Conversely, DHFR knockdown impaired MTX-treated adipose derived stem cell (ASC) osteogenesis. Proliferation of ASCs and bone marrow stem cells was more resistant to MTX than that of terminally differentiated osteoblasts. However, stem cells became susceptible to the drug after beginning differentiation. These results suggest that the ability of stem cells to survive and to maintain their surrounding tissues likely depends on whether they are in a "stem" state when exposed to MTX. Therapeutic strategies that delay the differentiation of stem cells until clearance of the drug may produce more favorable outcomes in the long-term health of treated tissues. PMID- 26815726 TI - Social Responsibility in Stem Cell Research - Is the News All Bad? AB - Transparent public discourse about translational stem cell research promotes informed hope about scientific progress and the sustainable development of biotechnologies. Using an a priori coding scheme, we surveyed articles from leading news media about stem cell interventions for neurodegenerative diseases (1991-2014) from United States (n = 83), Canada (n = 29), and United Kingdom (n = 65). While, this analysis of translational contexts in the news demonstrates a lingering tendency to celebrate the benefits of research with little context of its caveats even for chronic neurologic diseases, in a departure from many previous studies, the data also reveal conscientious reporting about stem cell tourism and timeframe estimates for the development of relevant therapeutics. PMID- 26815727 TI - Brief Report: Association of Rheumatoid Factor and Anti-Citrullinated Protein Antibody Positivity With Better Effectiveness of Abatacept: Results From the Pan European Registry Analysis. AB - OBJECTIVE: To investigate the role of rheumatoid factor (RF) status and anti citrullinated peptide antibody (ACPA) status as predictors of abatacept (ABA) effectiveness in patients with rheumatoid arthritis (RA). METHODS: We conducted a pooled analysis of data from 9 observational RA registries in Europe (ARTIS [Sweden], ATTRA [Czech Republic], BIOBADASER [Spain], DANBIO [Denmark], GISEA [Italy], NOR-DMARD [Norway], ORA [France], Reuma.pt [Portugal], and SCQM-RA [Switzerland]). Inclusion criteria were a diagnosis of RA, initiation of ABA treatment, and available information on RF and/or ACPA status. The primary end point was continuation of ABA treatment. Secondary end points were ABA discontinuation for ineffectiveness or adverse events and response rates at 1 year (good or moderate response according to the European League Against Rheumatism criteria with LUNDEX adjustment for treatment continuation). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the study end points in relation to RF and ACPA status were calculated. RESULTS: We identified 2,942 patients with available data on RA-associated autoantibodies; data on RF status were available for 2,787 patients (77.0% of whom were RF positive), and data on ACPA status were available for 1,903 patients (71.3% of whom were ACPA positive). Even after adjustment for sociodemographic and disease- and treatment-related confounders, RF and ACPA positivity were each associated with a lower risk of ABA discontinuation for any reason (HR 0.79 [95% CI 0.69-0.90], P < 0.001 and HR 0.78 [95% CI 0.68-0.90], P < 0.001, respectively), compared to RF-negative and ACPA negative patients. Similar associations with RF and ACPA were observed for discontinuation of ABA treatment due to ineffectiveness, with HRs of 0.72 (95% CI 0.61-0.84) and 0.74 (95% CI 0.62-0.88), respectively (both P < 0.001). CONCLUSION: Our results strongly suggest that positivity for RF or ACPA is associated with better effectiveness of ABA therapy. PMID- 26815728 TI - Specific excitonic interactions in the aggregates of hyaluronic acid and cyanine dyes with different lengths of methine group. AB - The absorption and circular dichroism (CD) spectra of three types of cyanine dyes with different lengths of methine group (3,3'-diethylthiadicarbocyanine iodide, DTDC; 3,3'-diethylthiacarbocyanine iodide, DTC; and 3,3'-diethylthiacyanine iodide, DTTHC) in an aqueous solution were compared with and without hyaluronic acid (HA), which has a helical structure. DTDC forms chiral H- and J-aggregates, whereas DTC and DTTHC are unable to form any aggregates. DTDC also forms H- and J aggregates in the presence of sodium polyacrylate (PA) with a random-coil structure; however, the PA-DTDC aggregates exhibit no chirality. These results suggest that the chirality of HA-DTDC aggregates is induced by the helical structure of HA. In 2.4 vol% and 10 vol% methanol, HA-DTDC aggregates displayed different patterns of temperature dependence, whereas no aggregation was observed in 30 vol% methanol. The solubility of DTDC in a mixed solvent of water and methanol is generally improved by the addition of methanol, which prevents the aggregation of DTDC. PMID- 26815729 TI - Lotus japonicus plants of the Gifu B-129 ecotype subjected to alkaline stress improve their Fe(2+) bio-availability through inoculation with Pantoea eucalypti M91. AB - Inoculation assays with Pantoea eucalypti M91 were performed on Lotus japonicus ecotype Gifu. Under alkaline conditions, this ecotype is characterized by the development of interveinal chlorosis of the apical leaves due to low mobilization of Fe(2+). Inoculation with P. eucalypti M91, a plant growth-promoting bacterial strain capable of producing pyoverdine-like and pyochelin-like siderophores under alkaline growth conditions, alters the root, resulting in a herringbone pattern of root branching. Additional features include improvement in Fe(2+) transport to the shoots, acidification of the hydroponic solution of the plant cultures, and an accompanying increase in the efficiency of the PSII parameters. In addition, there was an increase in the expression of the FRO1 and IRT1 genes, accompanied by a significant increase in FRO activity. Results showed that P. eucalypti M91 has a beneficial effect on the Fe acquisition machinery of Strategy I, as described for non-graminaceous monocots and dicots, suggesting its potential as an inoculant for legume crops cultivated in alkaline soils. PMID- 26815730 TI - Categorization Methodology: an Approach to the Collection and Analysis of Certain Classes of Qualitative Information. AB - A new methodology has been developed for the study of certain classes of qualitative information. The methodology is composed of two major techniques: the F-sort task for data collection and latent partition analysis for data summarization. In this paper, similarities and differences of the methodology in relation to existing techniques are discussed. This includes a review of the historical antecedents and development of the methodology as well as a listing of recent applications of the methodology, which have been in several fields of psychology and education. Following that review, a detailed presentation is given of how the methodology was applied to studying teachers' views of facilitating student learning in the classroom. In the data analysis, some previously unpublished enhancements of latent partition analysis are introduced -- for basic categorization statistics, recovery of subgroup information, and linkage to multidimensional scaling. This complete and substantively intriguing example is intended to illustrate the power and utility of the methodology in exploring important research topics. Then, examinations are made of the main components of the F-sort technique and of latent partition analysis. The intent is to lay out detailed frameworks for designing and interpreting research that applies the categorization methodology. The methodology has not previously been given an integrated description. Finally, discussion concerns the uses of the methodology and the importance of standardized application of the procedures. PMID- 26815731 TI - Rank and Normal Scores Alternatives to Hotelling's T(2). AB - Monte Carlo methods were used to compare the Type I error rates and powers of two sample multivariate rank and normal scores procedures to those of Hotelling's T(2). The 20 conditions investigated include heteroscedastic cases and nonnormal conditions in which the marginal densities were slightly leptokurtic and had a moderate negative skew. Results showed that under normal homoscedastic conditions, the parametric test was, as expected, the most powerful procedure. The parametric and rank tests were more powerful than the normal scores procedure in the normal heteroscedastic case. In the nonnormal homoscedastic conditions, the parametric and normal scores tests performed better than the rank procedure. In the nonnormal heteroscedastic case, the rank test was superior to its competitors. PMID- 26815732 TI - Factors Affecting the Frequency, Timing, and Sign of Informal Supervisory Feedback to Subordinates in a Simulated Work Setting. AB - Three critical characteristics of informal supervisory feedback to subordinates were defined which determine message effectiveness: frequency, timing and sign. Three potentially important determinants of these characteristics were identified (subordinate performance level, feedback mode, and supervisor-subordinate interdependence) and experimentally manipulated in a multivariate 2 x 2 x 2 factorial design. One-hundred male psychology students functioned as supervisors of four-man groups in a simulated work setting. Overall MANOVA results were highly significant. Follow-up ANOVA findings indicated that: (a) supervisors gave more frequent feedback to poor performers than to good ones, (b) feedback frequency was higher when the mode was written than face-to-face, and PMID- 26815733 TI - Note on the Relation between the Power of a Significance Test and the Reliability of the Measuring Instrument. AB - The relation between the power of a significance test in a block design with correlated measurements and the reliability of the measuring instrument has been the subject of a debate in the literature. This relation is further analyzed in terms of the components of variance entering the reliability coefficient and the noncentrality parameter. The function relating the true scores of alternative measuring instruments is considered. Power and reliability are positively related for linearly related true scores, and the relation is indeterminate, permitting on inverse relation for nonlinearly related true scores. The relevance of the distinction between the reliability study and the treatment study is discussed. PMID- 26815734 TI - Effectiveness of insole use in rheumatoid feet: a randomized controlled trial. AB - OBJECTIVES: To assess the effectiveness of foot orthoses with regard to pain, function, quality of life, and global perceived effect in patients with rheumatoid arthritis (RA). METHOD: A double-blind randomized controlled trial (RCT) was carried out. Eighty women with RA were randomly assigned to an experimental group (EG) or a control group (CG). The EG used an insole with metatarsal and medial arch supports and the CG used a flat insole for 6 months. Evaluations performed at baseline and after 45, 90, and 180 days by a blinded assessor were: foot pain while walking and at rest, function, quality of life, and global perceived effect with treatment. RESULTS: The groups were homogeneous for all parameters at baseline. A statistically significant improvement (p < 0.001) was found in the EG regarding pain while walking (mean difference: -2.2 for the right foot and -2.1 for the left foot) and at rest (mean difference: -0.3 for the right foot and -0.5 for the left foot) in comparison to CG. There were no differences in any other observed measures. The time of insole use correlated with foot pain and function in the EG. CONCLUSIONS: Foot orthoses with metatarsal and medial arch supports decreases pain during walking and at rest in both feet in patients with RA. Time of insole use correlated with improvements in pain and function. PMID- 26815735 TI - Ureteral stents are part of an ever-expanding technology horizon. PMID- 26815736 TI - A NiMoS flower-like structure with self-assembled nanosheets as high-performance hydrodesulfurization catalysts. AB - Uniform 3D NiMoS nanoflowers with self-assembled nanosheets were successfully synthesized via a simple hydrothermal growth method using cheap and nontoxic elemental sulfur as sulfur sources. The structure and morphology of the nanomaterials were characterized by SEM, TEM, XRD, Raman and XPS analyses, revealing that the NiMoS nanoflowers were composed of ultrathin nanosheets with a thickness of approximately 6-12 nm. The HRTEM results indicate that the curve/short MoS2 slabs on the nanosheets possess the characteristics of dislocations, distortions and discontinuity, which suggests a defect-rich structure, resulting in the exposure of additional Ni-Mo-S edge sites. The obtained NiMoS nanoflowers exhibited an excellent activity for thiophene hydrodesulfurization (HDS) and 4,6-dimethyldibenzothiophene deep HDS due to their high density of active sites. The outstanding HDS performance suggests that these NiMoS composites with a unique flower-like nanostructure could be useful as promising catalysts for deep desulfurization of fuel oils. PMID- 26815737 TI - Generation of coherent spin-wave modes in yttrium iron garnet microdiscs by spin orbit torque. AB - In recent years, spin-orbit effects have been widely used to produce and detect spin currents in spintronic devices. The peculiar symmetry of the spin Hall effect allows creation of a spin accumulation at the interface between a metal with strong spin-orbit interaction and a magnetic insulator, which can lead to a net pure spin current flowing from the metal into the insulator. This spin current applies a torque on the magnetization, which can eventually be driven into steady motion. Tailoring this experiment on extended films has proven to be elusive, probably due to mode competition. This requires the reduction of both the thickness and lateral size to reach full damping compensation. Here we show clear evidence of coherent spin-orbit torque-induced auto-oscillation in micron sized yttrium iron garnet discs of thickness 20 nm. Our results emphasize the key role of quasi-degenerate spin-wave modes, which increase the threshold current. PMID- 26815738 TI - Asymmetric Dimers of Chiral Azobenzene Dopants Exhibiting Unusual Helical Twisting Power upon Photoswitching in Cholesteric Liquid Crystals. AB - In this study, we synthesized asymmetric dimeric chiral molecules as photon-mode chiral switches for reversible tuning of self-assembled helical superstructures. The chiral switches bearing two mesogen units-cholesterol and azobenzene moieties connected through flexible alkylenedioxy bridges-were doped into nematic liquid crystals, resulting in a chiral nematic (cholesteric) phase. Under irradiation with UV light, photoisomerization of the azobenzene units led to unprecedented switching of the cholesteric pitch and helical twisting power (HTP, beta), with a higher HTP found in the cis-rich state (bent-form) than in the trans-state (rod form). We attribute this behavior to the elongated cybotactic smectic clusters disrupting the helical orientation of the molecules in the cholesteric liquid crystals; their reversible decay and reassembly was evidenced upon sequential irradiation with UV and visible light, respectively. In addition to the photoisomerization of the azobenzene units, the odd/even parity of the alkylenedioxy linkers of the dimeric dopants also had a dramatic effect on the transitions of the cybotactic smectic domains. On the basis of the large rotational reorganization of the cholesteric helix and HTP switching (Deltabeta/betaini of up to 50%), we could control the macroscopic rotational motion of microsized glass rods upon irradiating the surface of a cholesteric liquid crystal film featuring a polygonal fingerprint texture using UV and visible light. PMID- 26815739 TI - Impaired topological architecture of brain structural networks in idiopathic Parkinson's disease: a DTI study. AB - Parkinson's disease (PD) is considered as a neurodegenerative disorder of the brain central nervous system. But, to date, few studies adopted the network model to reveal topological changes in brain structural networks in PD patients. Additionally, although the concept of rich club organization has been widely used to study brain networks in various brain disorders, there is no study to report the changed rich club organization of brain networks in PD patients. Thus, we collected diffusion tensor imaging (DTI) data from 35 PD patients and 26 healthy controls and adopted deterministic tractography to construct brain structural networks. During the network analysis, we calculated their topological properties, and built the rich club organization of brain structural networks for both subject groups. By comparing the between-group differences in topological properties and rich club organizations, we found that the connectivity strength of the feeder and local connections are lower in PD patients compared to those of the healthy controls. Furthermore, using a network-based statistic (NBS) approach, we identified uniformly significantly decreased connections in two modules, the limbic/paralimbic/subcortical module and the cognitive control/attention module, in patients compared to controls. In addition, for the topological properties of brain network topology in the PD patients, we found statistically increased shortest path length and decreased global efficiency. Statistical comparisons of nodal properties were also widespread in the frontal and parietal regions for the PD patients. These findings may provide useful information to better understand the abnormalities of brain structural networks in PD patients. PMID- 26815741 TI - Soft Tissue: Infection and Reconstruction. PMID- 26815740 TI - MPT0B169, a New Antitubulin Agent, Inhibits Bcr-Abl Expression and Induces Mitochondrion-Mediated Apoptosis in Nonresistant and Imatinib-Resistant Chronic Myeloid Leukemia Cells. AB - Chronic myeloid leukemia (CML) is a clonal disorder of hematopoietic stem/progenitor cells that is caused by the Bcr-Abl oncoprotein. Clinical resistance to the Bcr-Abl inhibitor imatinib is a critical problem in treating CML. This study investigated the antitumor effect and mechanism of MPT0B169, a new antitubulin agent, in K562 CML cells and their derived imatinib-resistant cells, IMR2 and IMR3. IMR2 and IMR3 cells showed complete resistance to imatinib induced growth inhibition and apoptosis. Resistance involved ERK1/2 overactivation and MDR1 overexpression. MPT0B169 inhibited the growth of K562, IMR2, and IMR3 cells in a dose- and time-dependent manner. MPT0B169 substantially inhibited the mRNA and protein levels of Bcr-Abl, followed by its downstream pathways including Akt, ERK1/2, and STAT3 in these cells. MPT0B169 treatment resulted in a decrease in the polymer form of tubulin according to Western blot analysis. It triggered cell cycle arrest at the G2/M phase before apoptosis, which was related to the upregulation of the mitotic marker MPM2 and the cyclin B1 level, and a change in the phosphorylation of Cdk1. MPT0B169 induced apoptosis in nonresistant and imatinib-resistant cells via a mitochondrion-mediated caspase pathway. Further study showed that the agent led to a decrease in the antiapoptotic proteins Bcl-2, Bcl-xL, and Mcl-1 and an increase in the apoptotic protein Bax. Taken together, our results suggest that MPT0B169 might be a promising agent for overcoming imatinib resistance in CML cells. PMID- 26815742 TI - Necrotizing Fasciitis of the Perineum and the Abdominal Wall-Surgical Approach. AB - Necrotizing fasciitis is a synergistic aerobical-anaerobical infection that rapidly spreads from its origin leading to foudroyant increasing soft tissue gangrene and systemic sepsis. In the perineal, perianal and genital regions it is referred to as Fournier's gangrene constituting a clinical entity with the gangrene of the abdominal wall. After a short presentation of the own experience with 17 patients the surgical approach to the life-threatening disease is presented reviewing the former and the recent literature. There is a worldwide consensus that immediate radical excision of the gangrene should be accompanied by intensive care measures. Functional and cosmetic defects are to be reconstructed in a second stage. However, morbidity and mortality remain high in spite of consequent treatment due to often associated significant co-morbidity of affected patients. PMID- 26815743 TI - Necrotizing Fasciitis of the Extremities. AB - Necrotizing fasciitis (NF) describes a life threatening soft tissue infection characterized by a rapid spreading infection of the subcutaneous tissue and in particular the fascia. Various synonyms for this type of infection are used, often due to the difficult diagnosis. Necrotizing fasciits of the extremities is found after simple skin lacerations and often in rural, farming or garden setting environments. Many of the infections are found in immunologically healthy people, but persons revealing a compromised wound healing are endangered additionally, e.g., diabetes. In the majority of the microbiological analyses, streptococci alone or a mixture with mainly anaerobic bacteria may be detected. The management of infected extremities requires a rapid diagnosis, dedicated aggressive surgical management as soon as possible, and a wide debridement extending the border of the infected fascia. Timely surgical revisions within the first day or days together with antibiotic treatment are the only measures to stop the infection. Depending on the status of the patient a hyperbaric oxygenation treatment seems to be useful in order to limit the infection. In fulminated cases early amputations, maximal intensive care treatment of the septic patient are required, where all means are warranted to save the patients life. As a consequence, early clinical diagnoses with thorough surgical debridement of the infected liquid necrotic fascia as well as correct antibiotic treatment are needed. Secondary plastic reconstruction of the soft tissue defects will generally be required. PMID- 26815744 TI - Reconstructive Surgery after Compartment Syndrome of the Lower Leg and Foot. AB - Compartment syndrome at the lower extremity, if overlooked or treated inadequately in polytraumatized and multiply injured patients, regularly leads to progressive foot deformities and severe loss of function in the affected patients. The sequelae of compartment syndrome directly result from muscle contracture, necrosis and scarring and are further affected over time by gravity and posture (especially the sleeping position with the foot in equinus and inversion). While overlooked compartment syndrome of the lower leg leads to deformities of the whole foot, most frequently equinovarus, compartment syndrome of the foot results in painful toe deformities, mostly hammer or claw toes. Treatment aims at functional rehabilitation of the foot and ankle. Flexible deformities are treated with tendon lengthening or tendon transfer based on a thorough clinical evaluation of the remaining muscle force. Progressive contractures are subject to tenotomy, extensive capsular release and excision of scarred tissue. Corrective fusions should be reserved for long-standing deformities with symptomatic arthritis. They are combined with soft-tissue procedures as indicated. PMID- 26815745 TI - Delayed Presentations of Blunt Mesenteric and Intestinal Trauma in the Wake of Injury. AB - OBJECTIVE: To analyze the presentation and timing of blunt mesenteric and intestinal trauma requiring surgical intervention. METHODS: The Hadassah-Hebrew University trauma registry was scanned for patients who required surgery following blunt mesenteric and/or bowel trauma. Demographic data, mechanism of injury, time to diagnosis and pathology reports were recorded. A literature search was also performed. RESULTS: The majority of patients were injured in motor vehicle accidents (26/30, 86.7%). Patients were divided into three groups. Seventeen patients diagnosed within 4 h of admission were defined as the immediate group. Indication for surgery was hemodynamic instability and/or peritonitis. The most commonly injured region was the terminal ileum (10/17 patients, 59%). The second group (n = 4) had surgery within 2 weeks of injury (early group). These patients presented initially with hemodynamic instability. The operative findings were consistent with a low-flow state of the terminal ileum and cecum. The third group (n = 9) consisted of patients who were operated later than 2 weeks from the date of injury (late group). These patients presented with prolonged abdominal symptoms, chiefly partial small bowel obstruction. Operative findings were bowel strictures, most commonly of the terminal ileum (7/9 patients, 77.8%). CONCLUSIONS: Acceleration-deceleration abdominal injury affects the terminal ileum more commonly. We propose that the ensuing clinical picture depends on the level of energy transmitted: high-energy trauma leads to extensive mesenteric and bowel tears and is diagnosed immediately. Low-energy trauma may lead to chronic ischemia, fibrosis and stricture-formation. The right colon appears to be more vulnerable to lowflow states following blunt trauma. PMID- 26815746 TI - Multiple Trauma in Young and Elderly: Are There Any Differences? AB - BACKGROUND: Old age is considered a risk factor; however, its effect on the prognosis of injured elderly patients remains uncertain. AIM: To find the effect of old age on final outcome of elderly patients withmultiple trauma and to determine whether a different therapeutic approach is needed. METHODS: All patients with at least two injured body regions, as defined by the ISS, of grade 4 in AIS, were included. RESULTS: We studied 165 patients up to 64 years (Y) of age and 56 patients older than 65 years (E) in a 10-year period. On presentation 21.2% of Y and 25% of E, were hypovolemic (p = NS). No significant difference in number of injuries/patient was noted between Y and E patients, hemodynamically stable (HS) and unstable (HU) - (3.0 vs. 2.9 and 3.9 vs. 3.6). An increased relative frequency of chest and abdomen injuries was noted in Y and E, who died or were HU on presentation. A higher relative frequency of long bone and pelvis fractures was noted in the E. The ISS was not different among HS and HU, Y and E. Hospitalization in ICU was more common in E than in Y (69.6 vs. 47.3%), but there was no difference in the final outcome: overall mortality was 10.3% in Y versus 16.1% in E (p = NS), mortality in HU was 42.9% in Y versus 50% in E (p = NS). ISS was not associated with mortality in either group. CONCLUSIONS: Old age has no influence on final outcome of E multi trauma patients; hence, the therapeutic approach of these patients should be the same in Y. PMID- 26815747 TI - The Outcome of Cardiac Dysfunction in Critically Ill Trauma Patients: Myocardial Contusion Complicated by Refractory Hypotension. AB - BACKGROUND: This work attempted to define the care and course of those most severely affected patients in the setting of blunt chest trauma, who had hypotension refractory to routine fluid resuscitation. METHODS: Twenty-three critically ill blunt trauma ICU patients were resuscitated and enrolled with ongoing hypotension required placement of a pulmonary artery catheter. The REF((r))Explorer (Baxter, Edwards, Anaheim, CA) catheter was placed in the right heart measuring pressure, volume and oxygen utilization information, as well as recording Injury Severity Score, EKG, CXR, CPK/MB and echocardiography over the initial 72-h time period. RESULTS: There were an approximately 2,300 Level I trauma patients admitted annually over a 4-year period with an overall mortality rate of 4.3% (100) patients with 3.4% (79) patients "ruling in" with elevated cardiac enzymes, associated with an increased mortality rate of 6.7% (p < 0.05). The 23 patients were male (17, 74%), mean age 41.2 years, with no past medical history (19, 83%), in a motor vehicle accident (21, 91%), with pulmonary injury (9, 39%), undergoing celiotomy in (10, 44%). They presented with moderate to severe trauma acuity defined as mean GCS of 8.6, TS of 11.3, and ISS of 34 with an increased mean hospital stay of 15 days versus 6 days in the ICU; and a 26 days versus 10 days overall stay for those with myocardial contusion (p < 0.05). Analysis of diagnostic variables found an abnormal EKG in (21, 91%), CXR in (20, 87%) and echocardiogram in (8, 37%). The total CPK was found to be elevated, mean 2,219 (204-8,278 U/l), while the MB fraction was normal 2.3 +/- 1.3%. Invasive cardiac monitoring found an increase in CO of 1.6 l/min from 5.9 to 7.8 l/min during the first 24 h of recovery. Survival was worsened with increased ISS (29 vs. 43) p < 0.02, but improved with longer ICU (17 vs. 8) p < 0.03 and hospital (39 vs. 7) p < 0.05 stay in days. The analysis of commonly used diagnostic modalities - EKG, CXR, ECHO, or CO, did not correlate with survival, but the total CPK was increased in survivors (2,715 vs. 1,432 U/l) p < 0.009. CONCLUSION: There is worsened morbidity with a 2-fold increase in ICU LOS and hospital stay, and a 1.5-fold increase in mortality in the severe myocardial contusion group. The diagnostic dilemma posed by lack of definitive testing continues unresolved after analysis of routinemodalities - EKG, CXR, ECHO, CPK or CO - failing to yield a "best test". PMID- 26815748 TI - Pediatric Splenic Injury: Nonoperative Management First! AB - BACKGROUND AND PURPOSE: In the past splenectomy was the standard procedure for traumatic blunt splenic injury, when bleeding of the spleen occurred. Since the spleen performs important immunological functions the advantage of a spleen saving approach is preservation of immunological functions. Especially in the pediatric population splenic preservation is an important objective. Spleen saving treatment, in particular selective nonoperative management, has gained ground in the past 20 years. An 18-year retrospective review was performed to evaluate our cumulative experience with nonoperative management. ENDPOINTS: hemodynamical instability and splenectomy. METHODS: Forty-six patients were identified. Demographics, methods of management, mechanism of injury, injury grade, associated injuries, hemodynamical parameters, bloodtransfusion, complications, ICU and hospital stay were documented and analyzed to determine statistical significance between modes of management. RESULTS: Initially, 34 patients were managed nonoperatively, while 12 patients underwent laparotomy - with 7 (58.3% of the operative group) of these having splenectomy performed. Three patients (out of 34) failed nonoperative management and required delayed splenorraphy or splenectomy, a 91.2% (3 out of 34 failed) success rate for intended nonoperative management versus 85.7% for intended splenorraphy (1 out of 7 failed). Thus, overall rates of 67.4% nonoperative management and 82.6% splenic conservation were achieved. Analysis of parameters between treatments showed significant differences between nonoperative management and splenorraphy for splenic injury grade II and IV. CONCLUSION: We recommend based on our data on children with splenic injury grades II and IV that the standard treatment for children aged 0 to 18 years due to blunt abdominal trauma should be nonoperative management. However management of blunt splenic injury remains a clinical decision, for this reason does not preclude on CT-scan grade V for nonoperative management. PMID- 26815749 TI - Tip-Apex Distance as a Predictor of Failure Following Cephalo-Medullary Fixation for Unstable Fractures of the Proximal Femur. AB - Current research has been unable to confirm that intramedullary fixation provides greater stability for unstable fracture configurations of the proximal femur than extra-medullary devices. We present a retrospective analysis of the outcome of proximal femoral fractures treated with the Proximal Femoral Nail (PFN, Synthes) with particular reference to implant position and adequacy of reduction. Between May 2002 and October 2004, 61 patients with low-energy unstable proximal femoral fractures underwent surgery at a mean 2.4 days. Mean age was 78 years, 74% were female. Four (6.9%) implants failed secondary to proximal cut out of the hip screw. All of the failures occurred in patients who had sustained AO/OTA type 31. A3 fractures. In patients with A3 fracture patterns, there is a significant relationship between increasing Tip-Apex distance (p = 0.023), varus mal reduction (p = 0.038) and failure; 46% patients died within 12 months of surgery. The PFN is a satisfactory implant in the management of unstable proximal femoral fractures, however accurate reduction and implant position are essential to provide the best conditions for union and to prevent implant failure. PMID- 26815750 TI - Predicting Health-related Quality of Life of Severely Injured Patients: Sociodemographic, Economic, Trauma, and Hospital Stay-related Determinants. AB - INTRODUCTION: Due to remarkable improvements in emergency and intensive care medicine in the recent past, the mortality rate for severely injured patients is decreasing. Outcome research therefore should no longer focus only on questions of survival, but also on aspects of the quality of life after severe trauma. This study examined the long-term effect of different sociodemographic, economic, trauma, and hospital-related factors on the health-related quality of life (SF 36) of severely injured patients. PATIENTS AND METHODS: A written questionnaire was sent to 121 trauma patients who received treatment in two hospitals in Cologne/Northrhine-Westfalia between 1996 and 2001. The inclusion criteria were more than one injury and a sum of abbreviated injury score of the two worst injuries >= 6. The response rate after using the total-design-method was 77.6% (n = 90). RESULTS: Severely injured patients showed significant reductions for all subscales of the SF-36, on average 4 years after discharge on average, in comparison to a German norm population. Specifically, aspects of the physical component scale were dramatically reduced. Linear regressions controlling for time after discharge suggested that higher age, lower socioeconomic status, living together with a partner, and the severity of trauma and injury of extremities were significant predictors for a reduced quality of life, while satisfaction with the hospital stay had a positive effect. DISCUSSION: All in all, it is important to identify trauma- patients who will suffer a reduced quality of life. In so doing, it will be possible to take into account the specific circumstances of their recovery during medical treatment, care, and rehabilitation. PMID- 26815751 TI - Complex Hepatic Injuries: an Audit from a Tertiary Center. AB - BACKGROUND: Nonoperative management is being increasingly employed in the management of blunt hepatic injuries. PATIENTS AND METHODS: We analyzed patients with complex hepatic injuries over a period of 10 years (1996-2006). RESULTS: Two hundred and ten patients with blunt hepatic injury were admitted and 103 patients had complex liver injuries. The predominant mode of injury was road traffic accidents in 91.2%. The grade distribution of liver injuries was grade III (72.8%), grade IV (23.3%) and grade V (4.9%). Twenty-four patients (23.3%) underwent surgery for persistent hemodynamic instability, persistent fall in hemoglobin level, bile leaks and intra-abdominal collection with sepsis. Associated intra-abdominal injuries were present in 19.4%, and 58.4% had associated extra-abdominal injuries. The operative procedures included hepatectomy (1), suture hepatorraphy (12), T-tube drainage for bile duct injuries (5), perihepatic sponge and gel foam packing (9), liver abscess drainage (3), and resection and debridement of liver tissue in six patients. The mortality and morbidity in this series was 10.7 and 56.4%, respectively. Multiorgan failure was present in 5, single organ failure in 37, sepsis in 24, biliary complications in 16 and intra-abdominal collection in 17 patients. Endoscopic management for bile leaks was performed in five patients, image-guided pig-tail drainage for abscesses in 11 patients, while angioembolization was done in two patients for right hepatic artery bleed. The mortality was not significantly different in surgical and nonoperative groups but operated patients had significantly higher morbidity. CONCLUSIONS: Complex liver injuries can be managed successfully with conservative treatment in majority, with low mortality and acceptable morbidity. Surgery is reserved for selected indications. PMID- 26815752 TI - Percutaneous Dilational Tracheostomy in a Community Intensive Care Unit. AB - PURPOSE: Percutaneous dilational tracheostomy (PDT) is increasingly being used to replace traditional surgical tracheostomy (ST) in the management of critically ill patients. There is considerable controversy regarding the safety of this procedure in the hands of non-surgeons, and most data so far have come from large tertiary care centres. We report our experience and safety data in the implementation of a PDT program for critically ill patients in a teaching community hospital in an attempt to demonstrate that this procedure can be performed safely outside of an academic ICU. METHODS: Prospective observational study in a large community teaching hospital. All patients without contraindications were considered for enrollment. Contraindications to PDT included evidence of infection at the surgical site, the presence of a coagulopathy not correctable to an international normalized ratio of less than 1.5, or unstable cervical spine injuries. A total of 42 patients were included in the study and all received PDT using the Ciaglia Blue Rhino single dilator introducer set (Cook Critical Care, Bloomington, IN, USA). Data collected included patient age, sex, reason for intubation, and complications. RESULTS: Of 42 patients, 25 were males, and 17 were females. The average age was 47.6 years (range 16-87 years). The commonest admitting diagnosis was traumatic brain injury, followed by sepsis and cardiac arrest. Our total recorded complication rate was 7.1%, with no deaths. There were two episodes of transient hypotension (4.8%). CONCLUSION: Percutaneous dilational tracheostomy appears to be at least as safe as traditional ST, and may have advantages with respect to timeliness and minimization of patient transport. The complication rate seen in our program is similar to that seen in other PDT series. PMID- 26815753 TI - Chylothorax Resulting from a Penetrating Injury of the Neck: a Case Report. AB - Chylothorax is characterized by an accumulation of lymphatic fluid in the pleural cavity due to compression or loss of integrity of the thoracic duct for any reason. It is frequently secondary to intrathoracic malignancies and iatrogenic trauma. Thoracic duct injury and resulting chylothorax, due to penetrating injuries of the neck, are very rare. This report presents a patient with chylothorax associated with penetrating neck trauma, who was successfully treated, and provides discussion on this very rare case in the light of the available literature. PMID- 26815754 TI - Late Erosion of the Aorta after Dorsal-Ventral Care of a L1 Fracture with Prominent Chip Position. AB - Due to results of biomechanical examinations, the dorsal-ventral stabilization of thoracic spine and lumbar spine fractures is an acknowledged method. Different possible complications - among them life-threatening ones- of this method have been published already. We will discuss a complex case wherein an erosion of the aorta led to an acute hemorrhagic shock symptomatology 98 days after primary dorsal-ventral care. Retrospectively, an already close contact of the aorta to the pressed-in chip could be identified as the reason in a postoperative CT control after ventral care. However, due to a postoperative course of infection the chip position has been accepted as such and not been changed. But this difficult and complex etiopatology has shown that chip and respectively material positions with contact to adjacent soft tissue structure are not acceptable. PMID- 26815755 TI - Posttraumatic Intrasplenic Pseudoaneurysm with High-Flow Arteriovenous Fistula: New Lessons to Learn. AB - Intrasplenic pseudoaneurysm is a potentially lethal complication of abdominal trauma. We present the case of a 33-year-old patient with this particular complication diagnosed by CT-scan. Selective embolization was not possible due to its extraordinarily large size and finally splenectomy was performed. We review the English literature and discuss the particular role of the interventional radiologist to treat this entity. The interventional radiologist is the specialist who better estimates the success of embolization or the risk and possibility of delayed splenic rupture. Embolization of the arterial tributary to the pseudoaneurysm should be considered as the treatment of choice only when the diagnosis is made before rupture of the spleen and only in selected cases. Splenectomy always remains as an alternative treatment for high-risk pseudoaneurysms. PMID- 26815756 TI - Liver Transplantation for Post reperfusion Syndrome due to Surgical Packing of a Lacerated Liver. AB - The liver is the most frequently injured intra-abdominal organ and is the main cause of death in patients with abdominal injuries (mortality 10-15%). Grades III and IV liver injuries may present a complex problem to the surgeon. Several techniques to prevent exsanguination have been described including perihepatic packing, hepatic artery ligation, liver suturing or resection, and hepatectomy with transplantation. We report a case of a trauma patient who underwent perihepatic packing to control bleeding. Following pack removal, the patient developed severe cardiorespiratory depression resulting from postreperfusion syndrome requiring emergency total hepatectomy and liver transplantation. Types I III hepatic injuries can safely be treated conservatively. Complex injuries (types IV and V) result in significant mortality, often requiring operative intervention. Indications of transplantion are uncontrollable hemorrhage or irreversible liver dysfunction. Literature reports describe liver transplantation as a second line treatment of complications following initial treatment. Our patient underwent liver transplantation as a second line treatment. The decision to transplant was based on two pathologic findings, ischemic changes of the liver and sudden cardio-respiratory decompensation following restoration of the blood supply to the liver. Both complications are emergencies, leading to death if not recognized and treated instantly. A total hepatectomy with temporary portocaval shunt followed by liver transplantation immediately or at a later stage is a life saving treatment for such cases. PMID- 26815757 TI - Secondary Abdominal Compartment Syndrome in a Patientwith Isolated Extraperitoneal Injuries. AB - The abdominal compartment syndrome (ACS) is defined as increased intra-abdominal pressure (IAP) associated with adverse physiologic consequences. The ACS ismost commonly diagnosed in patients sustaining abdominal or pelvic trauma, or suffering some other intraabdominal hemorrhagic catastrophe. Recently, several groups have reported cases in which patients sustaining extra-abdominal trauma developed ACS following acute resuscitation with crystalloids or blood. This secondary ACS (SACS) appears to be related to resuscitation-induced bowel edema and ascites. SACS is a poorly understood and characterized syndrome where the increased intra-abdominal pressure occurs without abdominal injury. Timely diagnosis is difficult because of its low incidence and major trauma to other body regions. We report a fatal case of SACS, which progressed to necrotic and gangrenous large bowel. PMID- 26815758 TI - Treatment of Diffuse Pulmonary Hemorrhage with Factor VIIa. AB - Blunt thoracic trauma resulting in lung contusion with severe diffuse pulmonary hemorrhage and massive hemoptysis is rare and has a poor prognosis. Treatment options are limited. We report a case of the successful use of recombinant activated factor VII (NovoSevenTM) in the treatment of life-threatening diffuse pulmonary hemorrhage secondary to an isolated blunt force thoracic injury without relevant traumatic coagulopathy. PMID- 26815759 TI - The Approach to Suicide Bombing Attacks: Changing Concepts. AB - Suicide bombing attacks have emerged as a lethal weapon in the hands of terrorist groups. Our aim was to review the medical experience acquired in Israel, Spain, the United Kingdom and the United States in managing terrorist attacks, and prepare medical systems for the difficult task of managing these events. EMS protocols are amended to deal with a large number of victims in an urban setting who must be rapidly evacuated to a medical center where resuscitative as well as definitive care is delivered. A combination of extensive soft tissue damage caused by penetrating injuries, blast injury to the lungs and tympanic membranes, and burns are common among survivors. Preparation must include establishment of a clear chain-of-command lead by a general surgeon who manages the event and is responsible for decisions regarding OR preferences and ICU admissions. The emergency department is re-organized to handle the influx of numerous severely injured casualties. Professional personnel and resources are recruited and re directed away from routine tasks towards treating the victims. This is achieved by deferring non-urgent operations, procedures and imaging studies. Victims are frequently re-assessed and re-evaluated to control chaos, minimize missed injuries and ensure delivery of an adequate level of care. PMID- 26815760 TI - Isolated Gallbladder Injury after Blunt Abdominal Trauma: a Case Report and Review. AB - We describe a case of isolated gallbladder contusion after deceleration trauma. On admission, no evident signs of intra-abdominal injury were present. However, after 24 h observation an explorative laparotomy was performed because of persistent abdominal complaints. A contusion of the gallbladder wall was found with intraluminal haematoma and a cholecystectomy was performed. Isolated injury of the gallbladder after blunt trauma is extremely rare. Risk factors are distention of the gallbladder, deceleration trauma and the presence of a relatively mobile gallbladder. Clinical signs often are very subtle. Delayed presentation is common with signs of hemobilia or obstruction due to intraluminal clots. Ultrasound and computed tomography are suitable diagnostic tools. However, the diagnosis is often missed if no other injuries are present. Signs pointing to gallbladder injury are a collapsed gallbladder with pericholecystic fluid or a hydroptic gallbladder with intraluminal hematoma. Hepatobiliary scintigraphy or angiography might be necessary if additional injuries are suspected. The choice of treatment depends on the kind of injury. Contusion of the gallbladder allows conservative treatment, but in case of a rupture, surgery will be necessary. Accompanying bile duct injuries can be treated by endoscopic stenting. If active arterial bleeding is present, selective embolization can be performed. PMID- 26815761 TI - Oral manifestations in Kindler syndrome: case report and discussion of literature findings. AB - Kindler syndrome is a rare genetic disorder showing some predominant clinical manifestations, for example, trauma-induced blisters, progressive poikiloderma, skin atrophy, and photosensitivity. Oral manifestations are not commonly described and can be often misdiagnosed. This report describes the case of a female patient diagnosed with Kindler syndrome showing the classical clinical features affecting the skin, in addition to oral lesions manifesting as keratotic plaques and ulcers affecting the buccal mucosa, floor of the mouth, alveolar ridge, hard palate, and soft palate. An incisional biopsy was performed to confirm the diagnostic hypothesis of an autoimmune lesion possibly related with the syndrome. Knowledge about the possible manifestations of the Kindler syndrome is important to improve its management. PMID- 26815762 TI - Disappearing Post-Pneumonectomy Pleural Fluid without Bronchopleural Fistula. PMID- 26815764 TI - A Digital Vascular Malformation Masquerading as Synovitis. PMID- 26815763 TI - Molecular mechanism of phototropin light signaling. AB - Phototropin (phot) is a blue light (BL) receptor kinase involved in the BL responses of several species, ranging from green algae to higher plants. Phot converts BL signals from the environment into biochemical signals that trigger cellular responses. In phot, the LOV1 and LOV2 domains of the N-terminal region utilize BL for cyclic photoreactions and regulate C-terminal serine/threonine kinase (STK) activity. LOV2-STK peptides are the smallest functional unit of phot and are useful for understanding regulation mechanisms. The combined analysis of spectroscopy and STK activity assay in Arabidopsis phots suggests that the decay speed of the photo-intermediate S390 in LOV2 is one of the factors contributing to light sensitive kinase activity. LOV2 and STK are thought to be adjacent to each other in LOV2-STK with small angle scattering (SAXS). BL irradiation induces LOV2-STK elongation, resulting in LOV2 shifting away from STK. The N- and C terminal lateral regions of LOV2, A'alpha-helix, Jalpha-helix, and A'alpha/Abeta gap are responsible for the propagation of the BL signal to STK via conformational changes. The comparison between LOV2-STK and full-length phot from Chlamydomonas suggests that LOV1 is directly adjacent to LOV2 in LOV2-STK; therefore, LOV1 may indirectly regulate STK. The molecular mechanism of phot is discussed. PMID- 26815765 TI - Infants and young children modeling method for numerical dosimetry studies: application to plane wave exposure. AB - Numerical dosimetry studies require the development of accurate numerical 3D models of the human body. This paper proposes a novel method for building 3D heterogeneous young children models combining results obtained from a semi automatic multi-organ segmentation algorithm and an anatomy deformation method. The data consist of 3D magnetic resonance images, which are first segmented to obtain a set of initial tissues. A deformation procedure guided by the segmentation results is then developed in order to obtain five young children models ranging from the age of 5 to 37 months. By constraining the deformation of an older child model toward a younger one using segmentation results, we assure the anatomical realism of the models. Using the proposed framework, five models, containing thirteen tissues, are built. Three of these models are used in a prospective dosimetry study to analyze young child exposure to radiofrequency electromagnetic fields. The results lean to show the existence of a relationship between age and whole body exposure. The results also highlight the necessity to specifically study and develop measurements of child tissues dielectric properties. PMID- 26815766 TI - The Importance of Wild Canids in the Epidemiology of Rabies in Northeast Brazil: A Retrospective Study. AB - Rabies is an endemic disease in Brazil, where it is considered a serious public health problem. Although the number of human and dog-transmitted cases has declined in recent decades, rabies in wildlife has emerged considerably. Among the sylvatic animals, wild canids have been considered important hosts of the rabies virus. We performed a retrospective study of reported cases of rabies in wild canids and human victims in Ceara state (Northeast Brazil) during 2003 to 2013. Information was provided by governmental laboratories involved in rabies detection and by the Ministry of Health. From January 2003 to December 2013, a total of 11 931 animal samples were examined for rabies. Positivity were detected in 438 samples (3.67%), of which 229 (52.28%) were domestic animals, 105 (23.97%) wild canids and 104 (23.74%) other wild animals (bats, marmosets and raccoons). Approximately 33% of wild canids surveyed (n = 317) were positive for rabies. During the studied period, a total of 1923 attacks on humans by wild canids were registered. Males (n = 1405) were more affected than females (n = 520; 72.98% versus 27.01%), and the median age of all cases was 36.5 years. Injuries to individuals up to 19 years old corresponded to approximately 30% (n = 565) of all cases. Most of the victims lived in rural areas (72.46%; n = 1395), and the majority showed bites (81.13%; n = 1677) or scratches (12.23%; n = 253). Injuries were considered profound (52.1%; n = 1003), superficial (40.91; n = 788) or multiple with severe laceration (6.98%; n = 134). Only 1300 (67.53%) victims were enrolled for the complete rabies post-exposure prophylaxis scheme. Data from the present study confirm that wild canids are important hosts of rabies virus in northeastern Brazil and jeopardize rabies control in this area. Local authorities should focus their efforts in education of health professionals. In addition, strategies should be formulated to preserve wildlife. PMID- 26815767 TI - Permeative Amine Introduction for Very Weak Acid Detection in Ion Chromatography. AB - A permeative amine introduction device (PAID) is placed after a conventional KOH eluent-suppressed conductometric anion chromatography (SCAC) system. The PAID converts the suppressed eluites from the acid form to the corresponding ammonium salt (NR2H + HX -> NR2H2(+) + X(-)) and allows very weak acids HX (pKa >= 7.0) that cannot normally be detected by SCAC to be measured by a second conductivity detector following the PAID. Permeative reagent introduction is dilutionless, can be operated without pumps, and provides good mixing (baseline noise 0.8 nS/cm for 27 MUM diethylamine) with low band dispersion (as small as 30 MUL). Diethylamine (DEA) was chosen as the amine source due to its low pKb value (3.0), high vapor pressure, low toxicity, and low odor. The eluites are thus detected against a low diethylammonium hydroxide (DEAOH) background (5-31 MUS/cm) as negative peaks because the equivalent conductance of OH(-) is greater than that of X(-). Reducing the background DEA concentration enhances the detectability of traces of weak acids. Lower background [DEA] will limit the maximum concentration of analyte acids that can be determined; a general concept of peak width measurement at a fixed height is proposed as a solution. Trace impurities formed during electrodialytic suppression play a role in background noise; for the first time, we look at the nature of such impurities. The appearance of silicate in a sample put in a glass container as a function of pH can be readily followed. The maximum silica level in high purity type 1 water is 50 nM (1.40 MUg/L Si), which is a measurement challenge in particular. A large injection volume (1 mL) permits detection limits of 21 nM silicate, 3 nM taurine, 3 nM sulfide, and 13 nM cyanide. PMID- 26815768 TI - Transcriptome-wide identification of Rauvolfia serpentina microRNAs and prediction of their potential targets. AB - MicroRNAs (miRNAs) are small non-coding RNAs of ~ 19-24 nucleotides (nt) in length and considered as potent regulators of gene expression at transcriptional and post-transcriptional levels. Here we report the identification and characterization of 15 conserved miRNAs belonging to 13 families from Rauvolfia serpentina through in silico analysis of available nucleotide dataset. The identified mature R. serpentina miRNAs (rse-miRNAs) ranged between 20 and 22nt in length, and the average minimal folding free energy index (MFEI) value of rse miRNA precursor sequences was found to be -0.815 kcal/mol. Using the identified rse-miRNAs as query, their potential targets were predicted in R. serpentina and other plant species. Gene Ontology (GO) annotation showed that predicted targets of rse-miRNAs include transcription factors as well as genes involved in diverse biological processes such as primary and secondary metabolism, stress response, disease resistance, growth, and development. Few rse-miRNAs were predicted to target genes of pharmaceutically important secondary metabolic pathways such as alkaloids and anthocyanin biosynthesis. Phylogenetic analysis showed the evolutionary relationship of rse-miRNAs and their precursor sequences to homologous pre-miRNA sequences from other plant species. The findings under present study besides giving first hand information about R. serpentina miRNAs and their targets, also contributes towards the better understanding of miRNA mediated gene regulatory processes in plants. PMID- 26815769 TI - Investigation on the isoform selectivity of novel kinesin-like protein 1 (KIF11) inhibitor using chemical feature based pharmacophore, molecular docking, and quantum mechanical studies. AB - Kinesin-like protein (KIF11) is a molecular motor protein that is essential in mitosis. Removal of KIF11 prevents centrosome migration and causes cell arrest in mitosis. KIF11 defects are linked to the disease of microcephaly, lymph edema or mental retardation. The human KIF11 protein has been actively studied for its role in mitosis and its potential as a therapeutic target for cancer treatment. Pharmacophore modeling, molecular docking and density functional theory approaches was employed to reveal the structural, chemical and electronic features essential for the development of small molecule inhibitor for KIF11. Hence we have developed chemical feature based pharmacophore models using Discovery Studio v 2.5 (DS). The best hypothesis (Hypo1) consisting of four chemical features (two hydrogen bond acceptor, one hydrophobic and one ring aromatic) has exhibited high correlation co-efficient of 0.9521, cost difference of 70.63 and low RMS value of 0.9475. This Hypo1 is cross validated by Cat Scramble method; test set and decoy set to prove its robustness, statistical significance and predictability respectively. The well validated Hypo1 was used as 3Dquery to perform virtual screening. The hits obtained from the virtual screening were subjected to various scrupulous drug-like filters such as Lipinski's rule of five and ADMET properties. Finally, six hit compounds were identified based on the molecular interaction and its electronic properties. Our final lead compound could serve as a powerful tool for the discovery of potent inhibitor as KIF11 agonists. PMID- 26815770 TI - Saligenin cyclic-o-tolyl phosphate (SCOTP) induces autophagy of rat spermatogonial stem cells. AB - Tri-ortho-cresyl phosphate (TOCP) has been widely used as plasticizers, plastic softeners, and flame-retardants in industry, which can be metabolized to High toxic saligenin cyclic-o-tolyl phosphate (SCOTP). Our previous results found that TOCP could disrupt the seminiferous epithelium in the testis and induce autophagy of rat spermatogonial stem cells. Little is known about the toxic effect of SCOTP on rat spermatogonial stem cells. The present study showed that SCOTP decreased viability of rat spermatogonial stem cells in a dose-dependent manner. Both LC3 II and the ratio of LC3-II/LC3-I were significantly increased; autophagy proteins atg5 and Beclin 1 were also markedly increased after treatment with SCOTP, indicating SCOTP could induce autophagy of the cells. Ultrastructural observation under the transmission electron microscopy (TEM) indicated that there were autophagic vacuoles in the cytoplasm in the SCOTP-treated cells. However, cell cycle arrest was not observed by flow cytometry; and the mRNA levels of p21, p27, p53 and cyclin D1 in the cells were also not affected by SCOTP. Meanwhile, SCOTP didn't induce apoptosis of the cells. In summary, we showed that SCOTP could induce autophagy of rat spermatogonial stem cells, without affecting cell cycle and apoptosis. PMID- 26815771 TI - Focus on surgical care of the adolescent trauma patient. PMID- 26815772 TI - Elastic stable intramedullary nailing (ESIN) in the adolescent patient-perils, pearls, and pitfalls. AB - PURPOSE: Elastic stable intramedullary nailing (ESIN) has become the treatment of choice for diaphyseal long-bone fractures in children. This paper reviews the complications and limitations of this method which can occur when applying this osteosynthesis to patients within the adolescent age group. METHODS: Each topographic site where ESIN is used was analyzed individually and systematically. Technical errors, indicational problems, and mistakes during the rehabilitation process are pointed out and recommendations are given on how to avoid failure. RESULTS: ESIN can be safe and efficacious within certain limits also in the adolescent age group. Whenever errors and mistakes occur in combination, e.g., applying ESIN to a patient with a multi-fragmented fracture and a high body mass index (BMI), the adolescent age group is less forgiving to indicational "stretching" than the pediatric age group. CONCLUSIONS: The best prophylaxis for failure of ESIN is a stable and symmetric construct with correctly sized implants. This holds even more true for the adolescent patient. Using ESIN in difficult situations such as longitudinally unstable fractures, patients with a body weight >50 kg, or away from the diaphysis should be considered and followed up carefully. If possible, these patients should be treated in specialized pediatric trauma centers. PMID- 26815773 TI - The pediatric vs. the adolescent elbow. Some insight into age-specific treatment. AB - Almost 20 % of all long bone fractures in childhood and adolescents involve the elbow region. Physicians dealing with pediatric trauma cases on a regular basis must be familiar with the specific radiologic features of the elbow at every developmental stage. This includes the shape and the appearance of elbow ossification centers, and knowledge of age-specific injury patterns. In young children, lateral condyle and supracondylar fractures of the distal humerus are most common. Radial neck fractures, Monteggia's lesion and olecranon fractures appear in every age during growth. Bicondylar fractures of the distal humerus, capitellar fractures and radial head fractures almost solely occur after the tenth year. Treatment options depend on fracture type, age and demands and vary from immobilization to closed reduction and open reduction including internal fixation with different types of materials. Special circumstances to influence the treatment regimen in every single injury entity are discussed. Additionally, the most common malformations and nontraumatic diseases of the elbow region are mentioned. PMID- 26815774 TI - Knee injuries in children and adolescents. AB - As more children and adolescents are involved in sporting activities, the number of injuries to immature knees rises. We will focus on three entities: ruptures of the anterior cruciate ligament, patellar dislocation, and meniscal injuries. There is a trend in recent literature toward early reconstruction of the anterior cruciate ligament in children and adolescents. In this article, we will try to highlight the anatomic specialities and the diagnostic steps toward the correct diagnosis, review technical considerations and risks of the different surgical techniques, and present outcomes and offer a treatment recommendation. The treatment of patellar dislocation has changed considerably since we gained a better understanding of the unique anatomy of the patellofemoral joint. We will show diagnostic steps and risk factors for recurrent patellar dislocation, discuss conservative and different operative therapy options, and present a modified technique to achieve a dynamic reconstruction of the medial patellofemoral ligament without damage to the growth plates. Meniscal tears and discoid menisci are rare in comparison to the other injuries. We will herein explain what specialities in the anatomy should be considered in children and adolescents concerning the menisci, and present the diagnostic steps and treatment options available. PMID- 26815775 TI - Triplane fractures: do we need cross-sectional imaging? AB - INTRODUCTION: Diagnosis of Triplane fractures remains difficult in common practice. Aim of the study was the evaluation of the fracture pattern and the benefit of cross-sectional imaging in classification of Triplane-fractures. MATERIAL AND METHODS: A total of 27 pediatric patients treated for ankle fractures were identified from patient charts. Radiographic images of epiphyseal fractures (X-rays and additional cross-sectional imaging) were blinded evaluated by 13 observers to answer a specific questionnaire regarding type or fracture and treatment suggestion. RESULTS: There were seven Triplane-I and eight Triplane-II fractures. The other physeal ankle fracture group consisted of four patients with a Twoplane-fracture, five Salter-and-Harris (SH) II, one SH-III, and two SH-IV fracture. Accuracy of classification improved considerably depending on the experience of the observer in pediatric trauma care. Surgeons specialized in pediatric trauma care classified correctly with conventional X-rays in 48.1 % of all cases presented versus 31.5 % appropriate diagnosis by younger fellows. Accuracy in exact specification of Triplane-fractures was comparable lesser in younger fellows (31.1 vs. 22 %). Cross-sectional imaging improved classification of all fractures in both groups (75.6 % specialized vs. 47.3 % non specialized). Whereas availability of cross-sectional imaging improved treatment recommendation in specialized surgeons this benefit was not detectable for the doctors without specialization. Evaluation of fracture pattern showed a relatively stereotypical fracture pattern in Triplane-II fractures, whereas Triplane-I fractures were more variable. CONCLUSION: The additional information of cross-sectional imaging seems helpful for any physician in finding the right classification of a pediatric ankle fracture. However, the additive information appears especially viable for experienced surgeons to suggest the appropriate treatment. PMID- 26815776 TI - The impact of ETOH intoxication on the development of admission coagulopathy after traumatic brain injury: a prospective evaluation. AB - INTRODUCTION: Coagulopathy after severe traumatic brain injury (sTBI) results in a ten-fold increased risk of death. Our aim was to investigate the effect of ETOH intoxication on admission coagulopathy after sTBI. METHODS: Patients with sTBI [Glasgow Coma Scale <9 or evidence of intracranial pathology on computed tomography (CT)] from 1/2010 to 12/2011 were prospectively enrolled. Demographics, clinical characteristics, laboratory values, head CT scan findings, physical examination, injury severity indices, and interventions were recorded. ETOH blood levels were obtained. The incidence of admission coagulopathy was compared between patients who were ETOH-positive (ETOH+) and those who were ETOH negative (ETOH-). Logistic regression was performed to identify independent risk factors. RESULTS: A total of 216 patients were enrolled. 20.4 % were ETOH+. Admission coagulopathy was significantly lower for ETOH+ patients (15.9 vs. 39.0 %, adjusted p = 0.020). Prothrombin time (PT) and International Normalized Ratio (INR) on admission were significantly lower for ETOH+ patients (16.7 vs. 14.3, adjusted p = 0.016 and 1.35 vs. 1.13, adjusted p = 0.040, respectively). Injury Severity Score >=25, hypotension, and loss of gray/white differential were identified as independent risk factors for the development of admission coagulopathy. ETOH intoxication was the only protective predictor [AOR (95 % CI): 0.32 (0.12, 0.84), adjusted p = 0.021]. CONCLUSIONS: ETOH intoxication is associated with a lower incidence of admission coagulopathy in patients with sTBI. Further research is warranted. PMID- 26815777 TI - The impact of body mass index on treatment outcomes among traumatic brain injury patients in intensive care units. AB - PURPOSE: Obesity is a risk factor in treatment outcomes of critically ill patients. This study was conducted to determine the impact of obesity on the likelihood of recovery from traumatic brain injury (TBI) in intensive care unit (ICU) patients. METHODS: We carried out a prospective study on 115 head injury patients who were admitted to the ICU of Poursina Hospital, Rasht, in the one year period between July 2006 and June 2007. Obese patients (body mass index [BMI] >= 30 kg/m(2)) were compared with non-obese patients (BMI < 30 kg/m(2)). Demographic information, acute physiology and chronic health evaluation scores, Injury Severity Scores (ISS), Glasgow Coma Scale scores, and ICU mortality incidences were recorded. RESULTS: Obese patients had significantly higher ICU mortality rates compared to non-obese patients (p = 0.02). Furthermore, we observed a trend towards a higher ICU mortality rate in obese patients with ISS > 25 (p = 0.04). Moreover, obesity was associated with prolonged mechanical ventilation, ICU length of stay (ILOS), and hospital length of stay (HLOS) (p < 0.001). CONCLUSIONS: Obesity was associated with increased ICU mortality and prolonged dependency on mechanical ventilation, ILOS, and HLOS in patients with TBI. However, further prospective studies with larger sample sizes are needed to substantiate these findings. PMID- 26815778 TI - Psoas:lumbar vertebra index: central sarcopenia independently predicts morbidity in elderly trauma patients. AB - INTRODUCTION: Central sarcopenia as a surrogate for frailty has recently been studied as a predictor of outcome in elderly medical patients, but less is known about how this metric relates to outcomes after trauma. We hypothesized that psoas:lumbar vertebral index (PLVI), a measure of central sarcopenia, is associated with increased morbidity and mortality in elderly trauma patients. METHODS: A query of our institutional trauma registry from 2005 to 2010 was performed. Data was collected prospectively for the Pennsylvania Trauma Outcomes Study (PTOS). INCLUSION CRITERIA: age >55 years, ISS >15, and ICU LOS >48 h. Using admission CT scans, psoas:vertebral index was computed as the ratio between the mean cross-sectional areas of the psoas muscles and the L4 vertebral body at the level of the L4 pedicles. The 50th percentile of the psoas:L4 vertebral index value was determined, and patients were grouped into high (>0.84) and low (<=0.83) categories based on their relation to the cohort median. Primary endpoints were mortality and morbidity (as a combined endpoint for PTOS-defined complications). Univariate logistic regression was used to test the association between patient factors and mortality. Factors found to be associated with mortality at p < 0.1 were entered into a multivariable model. RESULTS: A total of 180 patients met the study criteria. Median age was 74 years (IQR 63-82), median ISS was 24 (IQR 18-29). Patients were 58 % male and 66 % Caucasian. Mean PLVI was 0.86 (SD 0.25) and was higher in male patients than female patients (0.91 +/- 0.26 vs. 0.77 +/- 0.21, p < 0.001). PLVI was not associated with mortality in univariate or multivariable modeling. After controlling for comorbidities, ISS, and admission SBP, low PLVI was found to be strongly associated with morbidity (OR 4.91, 95 % CI 2.28-10.60). CONCLUSIONS: Psoas:lumbar vertebral index is independently and negatively associated with posttraumatic morbidity but not mortality in elderly, severely injured trauma patients. PLVI can be calculated quickly and easily and may help identify patients at increased risk of complications. PMID- 26815779 TI - Refining the trauma triage algorithm at an Australian major trauma centre: derivation and internal validation of a triage risk score. AB - PURPOSE: To derive and internally validate a clinical prediction rule for trauma triage. METHODS: Ambulance presentations requiring trauma team activation between 2007 and 2011 at a single inner city major trauma centre were analysed. The primary outcome was major trauma, defined as Injury Severity Score >15, intensive care unit admission or in-hospital death. Demographic details, vital signs on arrival at hospital, mechanism of injury and injured body regions were used in the modelling process. Multivariable logistic regression was used on a randomly selected derivation sample. Receiver operating characteristic (ROC) analysis and Hosmer-Lemeshow tests were used to assess the discrimination and calibration of the derived model. The model was further tested using bootstrapping cross validation. RESULTS: A total of 3027 patients were identified. Predictors selected for the prediction model were age >=65 years (OR 1.58, 95 %CI 1.08-2.32, p = 0.02), abnormal vital signs (OR 3.72, 95 %CI 2.64-5.25), Glasgow Coma Scale score <=13 (OR 14, 95 %CI 9.23-23.34 p < 0.001), penetrating injury (OR 5.13, 95 %CI 2.76-9.54, p < 0.001), multiregion injury (OR 4.72 95 %CI 3.45-6.46, p < 0.001), falls (OR 1.51 95 %CI 1.06-2.15, p = 0.02) and motor vehicle crashes (OR 0.56, 95 %CI 0.35-0.90, p = 0.02). The ROC area under the curve (AUC) for the final model was 0.85 (95 %CI 0.83-0.87) with a Hosmer-Lemeshow test statistic p = 0.83. Bootstrapping cross-validation demonstrated an identical AUC. CONCLUSION: We have derived and internally validated a trauma risk prediction rule using trauma registry data. This may assist with the formulation of revised local and regional trauma triage protocols. External validation is required before implementation. PMID- 26815780 TI - Blunt bowel and mesenteric injuries detected on CT scan: who is really eligible for surgery? AB - BACKGROUND: There is no consensually accepted approach to the management of blunt bowel and mesenteric injuries. Surgery is required urgently in the case of bowel perforation or haemodynamic instability, but several patients can be treated non operatively. This study aimed to identify the risk factors for surgery in an initial assessment. METHODS: We retrospectively reviewed the medical charts and computed tomography (CT) scans of adult patients presenting with a blunt abdominal trauma to our centre between the years 2004 and 2011. We included only patients with a CT scan showing suspected injury to the mesentery or bowel. RESULTS: There were 43 patients (33 males and 10 females), with a mean Injury Severity Score (ISS) of 22. The most frequently suspected injuries based on a CT scan were mesenteric infiltrations in 40 (93 %) patients and bowel wall thickening in 22 (51 %) patients. Surgical therapy was required for 23 (54 %) patients. Four factors were independently associated with surgical treatment: a free-fluid peritoneal effusion without solid organ injury [adjusted odds ratio (OR) = 14.4, 95 % confidence interval (CI) [1.9-111]; p = 0.015], a beaded appearance of the mesenteric vessels (OR = 9 [1.3-63]; p = 0.027), female gender (OR = 14.2 [1.3-159]; p = 0.031) and ISS >15 (OR = 6.9 [1.1-44]; p = 0.041). Surgery was prescribed immediately for 11 (26 %) patients and with delay, after the failure of initially conservative treatment, for 12 (28 %) patients. The presence of a free-fluid peritoneal effusion without solid organ injury was also an independent risk factor for delayed surgery (OR = 9.8 [1-95]; p = 0.048). CONCLUSIONS: In blunt abdominal trauma, the association of a bowel and/or mesenteric injury with a peritoneal effusion without solid organ injury on an initial CT scan should raise the suspicion of an injury requiring surgical treatment. Additionally, this finding should lead to a clinical discussion of the benefit of explorative laparotomy to prevent delayed surgery. However, these findings need validation by larger studies. PMID- 26815781 TI - The falling bullets: post-Libyan revolution celebratory stray bullet injuries. AB - OBJECTIVE: To report our experience with the post-Libyan revolution celebratory stray bullet injuries by falling bullets. METHODS: This descriptive study was carried out during the period from November 2011 to February 2012 at the military Jordanian field hospital in Benghazi-Libya. Twenty-three patients who were injured by falling bullets were enrolled in this study. Intentional and direct bullet injuries due to conflicts were excluded. Demographic data, injured body part, place of injury, timing of intervention, hospital stay, and fatality were described and analyzed. RESULTS: Children less than 14 years of age constituted 65.2 % (n = 15) of the falling bullets victims. Injured body parts were upper and lower limbs (12, 52.2 %), chest (8, 34.8 %), head and neck (2, 8.7 %), and abdomen (1, 4.3 %). Three (13.0 %) patients were diagnosed to have stray bullet injury by radiological investigations without a clinical suspicion. Two (8.7 %) fatalities were reported. CONCLUSION: Celebratory stray bullet injuries are an unusual form of injury not infrequently seen in some parts of the world. Lower limb and chest injuries especially among children are most commonly reported. Focus on prevention through education and weapon use regulations carries the best chance of reducing these injuries. PMID- 26815782 TI - Fast Track by physician assistants shortens waiting and turnaround times of trauma patients in an emergency department. AB - PURPOSE: We sought to determine whether the introduction of a separate patient flow comprising patients with simple, non-complex health issues [Fast Track (FT)] in a Dutch emergency department setting (ED), without the introduction of additional staff, and treated by a physician assistant, would have favourable effects on waiting and turnaround times without deleterious effects for patients with a higher urgency. STUDY DESIGN: We used a prospective comparative intervention design for our study. METHODS: The waiting times and length of stay for surgical and orthopaedic patients in the ED were measured and compared 3 months before and 3 months after the introduction of FT. RESULTS: During the study period, 1,289 patients were treated before, and 1,393 after the introduction of FT. After the introduction of FT, we observed a decrease of 12 min (13 %) in the median length of stay for the total group. The median waiting time decreased by 41 min (69 %). The group comprising patients with low to moderate urgency levels showed a median reduction of 12 min in length of stay, whereas the length of stay for urgent patients was reduced by 19 min. The waiting time for the low to moderate urgency patients decreased by 68 min, while the urgent patient group showed a reduction of 32 min. CONCLUSIONS: The introduction of FT performed by a physician assistant resulted in a significant drop in waiting time and length of stay in a Dutch ED setting. This reduction was realised without the allocation of additional staff and even reduced waiting and turnaround times for the patients with a high urgency. PMID- 26815783 TI - The early bird catches the worm - register early and save up to 80 euros. PMID- 26815784 TI - Osteogenesis Imperfecta Type VI in Individuals from Northern Canada. AB - Osteogenesis imperfecta (OI) type VI is a recessively inherited form of OI that is caused by mutations in SERPINF1, the gene coding for pigment-epithelium derived factor (PEDF). Here, we report on two apparently unrelated children with OI type VI who had the same unusual homozygous variant in intron 6 of SERPINF1 (c.787-10C>G). This variant created a novel splice site that led to the in-frame addition of three amino acids to PEDF (p.Lys262_Ile263insLeuSerGln). Western blotting showed that skin fibroblasts with this mutation produced PEDF but failed to secrete it. Both children were treated with intravenous bisphosphonates, but the treatment of Individual 1 was switched to subcutaneous injections of denosumab (dose 1 mg per kg body weight, repeated every 3 months). An iliac bone sample obtained after 5 denosumab injections (and 3 months after the last injection) showed no change in the increased osteoid parameters that are typical of OI type VI, but the number of osteoclasts in trabecular bone was markedly increased. This suggests that the effect of denosumab on osteoclast suppression is of shorter duration in children with OI type VI than what has previously been reported on adults with osteoporosis. PMID- 26815785 TI - [Orofacial pain - Trigeminal neuralgia and posttraumatic trigeminal neuropathy: Common features and differences]. AB - Neuropathic pain is the result of a lesion or disease of the somatosensory system in the peripheral or central nervous system. Classical trigeminal neuralgia and posttraumatic trigeminal neuropathy are pain disorders which oral and maxillofacial surgeons and dentists are confronted with in the differential diagnostics in routine daily practice. The etiopathogenesis of classical trigeminal neuralgia is attributable to pathological blood vessel-nerve contact in the trigeminal nerve root entry zone to the brain stem. The typical pain symptoms are characterized by sudden stabbing pain attacks. The pharmaceutical prophylaxis is based on the individually titrated administration of anticonvulsant drugs. The indications for interventional treatment are dependent on the course, response to drug treatment, resilience and wishes of the patient. The neuropathic mechanism of posttraumatic trigeminal neuropathy originates from nerve damage, which leads to peripheral and central sensitization with lowering of the pain threshold and multiple somatosensory disorders. The prophylaxis consists of avoidance of excessive acute and long-lasting pain stimuli. Against the background of the biopsychosocial pain model, the treatment of posttraumatic trigeminal neuropathy necessitates a multimodal, interdisciplinary concept. PMID- 26815786 TI - Alterations in white matter volume and integrity in obesity and type 2 diabetes. AB - Type 2 diabetes mellitus (T2DM) is characterized by obesity, hyperglycemia and insulin resistance. Both T2DM and obesity are associated with cerebral complications, including an increased risk of cognitive impairment and dementia, however the underlying mechanisms are largely unknown. In the current study, we aimed to determine the relative contributions of obesity and the presence of T2DM to altered white matter structure. We used diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) to measure white matter integrity and volume in obese T2DM patients without micro- or macrovascular complications, age- gender- and BMI-matched normoglycemic obese subjects and age- and gender-matched normoglycemic lean subjects. We found that obese T2DM patients compared with lean subjects had lower axial diffusivity (in the right corticospinal tract, right inferior fronto-occipital tract, right superior longitudinal fasciculus and right forceps major) and reduced white matter volume (in the right inferior parietal lobe and the left external capsule region). In normoglycemic obese compared with lean subjects axial diffusivity as well as white matter volume tended to be reduced, whereas there were no significant differences between normoglycemic obese subjects and T2DM patients. Decreased white matter integrity and volume were univariately related to higher age, being male, higher BMI, HbA1C and fasting glucose and insulin levels. However, multivariate analyses demonstrated that only BMI was independently related to white matter integrity, and age, gender and BMI to white matter volume loss. Our data indicate that obese T2DM patients have reduced white matter integrity and volume, but that this is largely explained by BMI, rather than T2DM per se. PMID- 26815787 TI - Specific Hsp100 Chaperones Determine the Fate of the First Enzyme of the Plastidial Isoprenoid Pathway for Either Refolding or Degradation by the Stromal Clp Protease in Arabidopsis. AB - The lifespan and activity of proteins depend on protein quality control systems formed by chaperones and proteases that ensure correct protein folding and prevent the formation of toxic aggregates. We previously found that the Arabidopsis thaliana J-protein J20 delivers inactive (misfolded) forms of the plastidial enzyme deoxyxylulose 5-phosphate synthase (DXS) to the Hsp70 chaperone for either proper folding or degradation. Here we show that the fate of Hsp70 bound DXS depends on pathways involving specific Hsp100 chaperones. Analysis of individual mutants for the four Hsp100 chaperones present in Arabidopsis chloroplasts showed increased levels of DXS proteins (but not transcripts) only in those defective in ClpC1 or ClpB3. However, the accumulated enzyme was active in the clpc1 mutant but inactive in clpb3 plants. Genetic evidence indicated that ClpC chaperones might be required for the unfolding of J20-delivered DXS protein coupled to degradation by the Clp protease. By contrast, biochemical and genetic approaches confirmed that Hsp70 and ClpB3 chaperones interact to collaborate in the refolding and activation of DXS. We conclude that specific J-proteins and Hsp100 chaperones act together with Hsp70 to recognize and deliver DXS to either reactivation (via ClpB3) or removal (via ClpC1) depending on the physiological status of the plastid. PMID- 26815788 TI - Minimization of Childhood Maltreatment Is Common and Consequential: Results from a Large, Multinational Sample Using the Childhood Trauma Questionnaire. AB - Childhood maltreatment has diverse, lifelong impact on morbidity and mortality. The Childhood Trauma Questionnaire (CTQ) is one of the most commonly used scales to assess and quantify these experiences and their impact. Curiously, despite very widespread use of the CTQ, scores on its Minimization-Denial (MD) subscale originally designed to assess a positive response bias-are rarely reported. Hence, little is known about this measure. If response biases are either common or consequential, current practices of ignoring the MD scale deserve revision. Therewith, we designed a study to investigate 3 aspects of minimization, as defined by the CTQ's MD scale: 1) its prevalence; 2) its latent structure; and finally 3) whether minimization moderates the CTQ's discriminative validity in terms of distinguishing between psychiatric patients and community volunteers. Archival, item-level CTQ data from 24 multinational samples were combined for a total of 19,652 participants. Analyses indicated: 1) minimization is common; 2) minimization functions as a continuous construct; and 3) high MD scores attenuate the ability of the CTQ to distinguish between psychiatric patients and community volunteers. Overall, results suggest that a minimizing response bias-as detected by the MD subscale-has a small but significant moderating effect on the CTQ's discriminative validity. Results also may suggest that some prior analyses of maltreatment rates or the effects of early maltreatment that have used the CTQ may have underestimated its incidence and impact. We caution researchers and clinicians about the widespread practice of using the CTQ without the MD or collecting MD data but failing to assess and control for its effects on outcomes or dependent variables. PMID- 26815789 TI - Oculomotor Deficits after Chemotherapy in Childhood. AB - Advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. However, reports suggest that some of the chemotherapy agents used for treatment can cross the blood brain barrier which may lead to a host of neurological symptoms including oculomotor dysfunction. Whether chemotherapy at young age causes oculomotor dysfunction later in life is unknown. Oculomotor performance was assessed with traditional and novel methods in 23 adults (mean age 25.3 years, treatment age 10.2 years) treated with chemotherapy for a solid malignant tumor not affecting the central nervous system. Their results were compared to those from 25 healthy, age-matched controls (mean age 25.1 years). Correlation analysis was performed between the subjective symptoms reported by the chemotherapy treated subjects (CTS) and oculomotor performance. In CTS, the temporal control of the smooth pursuit velocity (velocity accuracy) was markedly poorer (p<0.001) and the saccades had disproportionally shorter amplitude than normal for the associated saccade peak velocity (main sequence) (p = 0.004), whereas smooth pursuit and saccade onset times were shorter (p = 0.004) in CTS compared with controls. The CTS treated before 12 years of age manifested more severe oculomotor deficits. CTS frequently reported subjective symptoms of visual disturbances (70%), unsteadiness, light-headedness and that things around them were spinning or moving (87%). Several subjective symptoms were significantly related to deficits in oculomotor performance. To conclude, chemotherapy in childhood or adolescence can result in severe oculomotor dysfunctions in adulthood. The revealed oculomotor dysfunctions were significantly related to the subjects' self-perception of visual disturbances, dizziness, light-headedness and sensing unsteadiness. Assessments of oculomotor function may, thus, offer an objective method to track and rate the level of neurological complications following chemotherapy. PMID- 26815791 TI - Racial and Ethnic Disparities in the Pregnancies of Women With Systemic Lupus Erythematosus. AB - OBJECTIVE: Both systemic lupus erythematosus (SLE; lupus) and pregnancy individually have significant racial disparities, with black women experiencing higher rates of complications, yet no large studies have focused on the impact of race/ethnicity on pregnancy outcomes among women with lupus. METHODS: Using the Nationwide Inpatient Sample (NIS) for 2008-2010, pregnancy delivery discharges were identified and pregnancy outcomes were compared for women with lupus by maternal race/ethnicity. Adjusted odds ratios were used to compare pregnancy outcomes between black and white or Hispanic and white women with lupus. RESULTS: In this period, the NIS included 13,553 deliveries with lupus and 12,510,565 deliveries without lupus. Compared to white women with lupus, black and Hispanic women had higher rates of chronic hypertension, chronic renal failure, pneumonia, and acute renal failure. There was a high degree of pregnancy complication in all women with lupus, but especially in black and Hispanic women, with more than 40% cesarean-section delivery; preterm labor in 14.3% of white, 24.7% of black (odds ratio [OR] 1.97), and 20.6% of Hispanic (OR 1.56) deliveries; and preeclampsia and gestational hypertension in almost 20% of black and Hispanic pregnancies. After adjustment for predictors of pregnancy outcomes and racial differences in nonlupus pregnancy, black and Hispanic women with lupus had higher than expected rates of preeclampsia, preterm labor, and fetal growth restriction. CONCLUSION: Black and Hispanic women with lupus have disproportionately poor pregnancy outcomes. This study suggests that identifying the key causes of these differences and targeting interventions to the women of greatest need is an essential next step. PMID- 26815790 TI - Novel Monoclonal Antibody and Peptide Binders for Mycobacterium avium subsp. paratuberculosis and Their Application for Magnetic Separation. AB - The generation of novel Mycobacterium avium subsp. paratuberculosis (MAP) specific monoclonal antibodies and phage-display derived peptide binders, along with their application for the magnetic separation (MS) of MAP cells, is described. Our aim was to achieve even greater MAP capture capability than is possible with peptide-mediated magnetic separation (PMS) using a 50:50 mix of biotinylated-aMp3 and biotinylated-aMptD peptide-coated beads. Gamma-irradiated whole MAP cells and ethanol extracted antigens (EEA) from these cells were used to elicit an immune response and as phage-display biopanning targets. A range of novel binders was obtained and coated onto paramagnetic beads, both individually and in various combinations, for MS evaluation. IS900 PCR was employed after MS to provide quick results. Capture sensitivity was assessed using a range of MAP concentrations after which the most promising beads were tested for their specificity for MAP, by performing MS followed by culture using 10 other Mycobacterium species. Magnetic beads coated with the biotinylated EEA402 peptide demonstrated a greater level of MAP capture than the current PMS method, even when low numbers of MAP (<10 cfu/ml) were present; however these beads also captured a range of other mycobacteria and so lacked capture specificity. Magnetic beads coated with monoclonal antibodies 6G11 and 15D10 (used as a 50:50 mix or as dually coated beads) also demonstrated improved MAP capture relative to the current PMS method, but with little cross-reactivity to other Mycobacterium spp. Therefore, two new MS protocols are suggested, the application of which would be dependent upon the required endpoint. Biotinylated EEA402-coated beads could potentially be used with a MAP-specific PCR to ensure detection specificity, while beads coated with 6G11 and 15D10 monoclonal antibodies could be used with culture or the phage amplification assay. PMID- 26815792 TI - Asymmetric Michael Additions of 4-Hydroxycoumarin to beta-Nitrostyrenes with Chiral, Bifunctional Hydrogen-Bonding Catalysts. AB - Enantioselective Michael additions of 4-hydroxycoumarin to beta-nitrostyrenes are catalyzed by different chiral, bifunctional hydrogen-bonding catalysts, based on thiourea- and squaramide motifs. The scope of the catalysis is tested by employing a series of substituted beta-nitrostyrenes as well as different solvents. The 3,5-bis(trifluoromethyl)phenyl- and quinine-substituted squaramide catalyst is shown to be the most selective catalyst, resulting in 78% yield and 81% ee. Computational analyses of transition structures with different binding modes show that the most favored transition structure exhibits squaramide (NH)2 binding to an oxygen atom of the enolate nucleophile, while the nitroalkene coordinates via hydrogen bonding to the ammonium function of the quinuclidine unit of the catalyst. Hence, the canted directionality of the squaramide (NH)2 motif, favoring one-atom binding, might be decisive for the selectivity of the reaction. The absolute configuration of the major (-)-(R) enantiomer of the product is assigned computationally according to its optical rotation. PMID- 26815793 TI - How to Submit a Publishable Manuscript. PMID- 26815794 TI - Behavioral and Psychosocial Health of New Mothers and Associations With Contextual Factors and Perceived Health. AB - OBJECTIVE: To test the association of behavioral and psychosocial health domains with contextual variables and perceived health in ethnically and economically diverse postpartum women. DESIGN: Mail survey of a stratified random sample. SETTING: Southwestern community in Texas. PARTICIPANTS: Non-Hispanic White, African American, and Hispanic women (N = 168). METHODS: A questionnaire was sent to a sample of 600 women. The adjusted response rate was 32.8%. The questionnaire covered behavioral (diet, physical activity, smoking, and alcohol use) and psychosocial (depression symptoms and body image) health, contextual variables (race/ethnicity, income, perceived stress, and social support), and perceived health. Hypotheses were tested using linear and logistic regression. RESULTS: Body image, dietary behaviors, physical activity behaviors, and depression symptoms were all significantly correlated (Spearman rho = -.15 to .47). Higher income was associated with increased odds of higher alcohol use (more than 1 drink on 1 to 4 days in a 14-day period). African American ethnicity was correlated with less healthy dietary behaviors and Hispanic ethnicity with less physical activity. In multivariable regressions, perceived stress was associated with less healthy dietary behaviors, increased odds of depression, and decreased odds of higher alcohol use, whereas social support was associated with less body image dissatisfaction, more physical activity, and decreased odds of depression. All behavioral and psychosocial domains were significantly correlated with perceived health, with higher alcohol use related to more favorable perceived health. In regressions analyses, perceived stress was a significant contextual predictor of perceived health. CONCLUSION: Stress and social support had more consistent relationships to behavioral and psychosocial variables than race/ethnicity and income level. PMID- 26815795 TI - Experiences of Nurses Who Care for Women After Fetal Loss. AB - OBJECTIVE: To examine the experiences of, meaning for, and personal consequences for obstetric, emergency, and surgical nurses caring for women after fetal death and to determine how these nurses use Swanson's caring processes in providing such care. DESIGN: Four focus groups. SETTING: Two hospitals within the same health care system. PARTICIPANTS: Registered nurses (N = 24) working in the obstetric, surgery, or emergency departments. METHODS: Swanson's Theory of Caring guided focus group questions that were audiotaped and transcribed verbatim. Data were analyzed using a continuously emergent process of data collection, data reduction, data display, and interpretation. RESULTS: All participants demonstrated all of Swanson's caring processes but used them preferentially according to situational exigencies and level of rapport with each woman. Nurses had positive and negative feelings associated with caring for women after fetal loss. CONCLUSIONS: Obstetric nurses provided relatively equal focus on all processes in the Theory of Caring except Maintaining Belief. Surgical and emergency department nurses focused primarily on the caring processes of Knowing and Doing For. The negative feelings reported by nurses mirror some emotions commonly associated with compassion fatigue. More research is needed to determine whether nurses caring for mothers experiencing fetal loss are at risk for compassion fatigue. Research is also needed to identify strategies and interventions to help nurses so they may continue to give the best care possible to these very vulnerable families without detriment to themselves. PMID- 26815796 TI - Exploring Fear of Childbirth in the United States Through a Qualitative Assessment of the Wijma Delivery Expectancy Questionnaire. AB - OBJECTIVE: To explore women's experiences while completing the Wijma Delivery Expectancy Questionnaire (W-DEQ), an instrument used to measure fear of childbirth, and to analyze the readability and applicability of the instrument within a diverse population of women in the United States. DESIGN: Qualitative descriptive study using focus groups with women who were pregnant or had given birth in the last 5 years. SETTING: Urban health center in the Detroit metropolitan area. PARTICIPANTS: Participants included 22 women who participated in three focus groups. METHODS: Focus groups were used to collect data, which were analyzed using content analysis. The Fry Readability Graph, in computer form, was used to rate the readability of the instrument. RESULTS: Women in the focus groups identified many themes that were consistent with previous research. However, the women indicated many new factors that contributed to their fear that were previously unidentified by the W-DEQ, including fear of abandonment by their clinicians and fear of how the structure of the maternity care system affects care during childbirth. CONCLUSION: The findings from the focus groups challenge the utility and appropriateness of the W-DEQ for use as a screening tool to identify women who are pregnant and experiencing FOC in a U.S. PMID- 26815797 TI - Timing of Newborn Pulse Oximetry Screenings for Critical Congenital Heart Defects Before Discharge. AB - OBJECTIVE: To determine if there would be positive results from a second pulse oximetry screening (POS) completed for newborns at discharge at 28 to 48 hours of age in addition to the newborn POS completed at 24 to 25 hours of age. DESIGN: Prospective descriptive research study. SETTING: Rural, mid-Atlantic, 13-bed, level I hospital. PARTICIPANTS: Newborns (N = 1,002) at 35 weeks' gestation or older discharged from the newborn nursery. METHODS: Registered nurses (RNs) performed POS at 24 to 25 hours of age (POS 1) and at discharge but less than 48 hours of age (POS 2). Data related to critical congenital heart defects were collected. RESULTS: There were no positive POS results (O2 saturation <= 90%) at POS 1 or POS 2, and no additional diagnostic tests were ordered as a result of POS. Although one full-term newborn had negative results at POS 1 and POS 2, the RN identified a murmur, and a subsequent echocardiogram was used to detect tetralogy of Fallot and pulmonary atresia. The RNs detected concerning conditions in 14 newborns that resulted in 28 additional tests, including echocardiograms (9), chest x-ray imaging (8), laboratory testing (7), electrocardiograms (3), and ultrasound imaging (1). CONCLUSIONS: The POS-positive result rate was 0 for newborns at POS 1 and POS 2. Therefore, our study findings supported Maryland's mandate of one POS completed within 24 to 48 hours of birth. Nurses must continue to be vigilant about assessing newborns, including screening for critical congenital heart defects and congenital heart defects. PMID- 26815799 TI - Reactions of Low-Income African American Women to Breastfeeding Peer Counselors. AB - OBJECTIVE: To examine the influence of breastfeeding peer counseling on the breastfeeding experiences of African American mothers who participated in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). DESIGN: Qualitative study using focus groups. SETTING: Two WIC clinics in Southeast Wisconsin were used for recruitment and data collection. PARTICIPANTS: A convenience sample of nine African American mothers participated in one of two focus groups. METHODS: The women responded to a series of open-ended questions about their breastfeeding experiences and the effect of breastfeeding peer counselors (BPCs). Content and thematic analyses were used to analyze patterns related to the influence of BPCs on breastfeeding. RESULTS: Four themes were categorized: Educating With Truth, Validating for Confidence, Countering Others' Negativity, and Supporting With Solutions. Mothers in this study expressed positive reactions to educational, emotional, and social support from BPCs. The mothers noted that the contact they had with BPCs had a direct positive influence on their breastfeeding experiences. However, the contact from BPCs varied between the two WIC clinics. CONCLUSION: The findings demonstrate the positive effects of BPCs on breastfeeding experiences among African American WIC participants. Findings from this study can guide future explorations using BPCs. Interventions are needed to develop standardized guidelines to bring about homogeneity of, better access to, and greater use of BPCs. PMID- 26815798 TI - A Test of Kangaroo Care on Preterm Infant Breastfeeding. AB - OBJECTIVE: To test the effects of kangaroo care (KC) on breastfeeding outcomes in preterm infants compared with two control groups and to explore whether maternal infant characteristics and the mother's choice to use KC were related to breastfeeding measures. DESIGN: Secondary analysis of a multisite, stratified, randomized three-arm trial. The treatment groups used KC, auditory-tactile-visual vestibular (ATVV) intervention, or received preterm infant care information. SETTING: Neonatal intensive care units from 4 hospitals in the United States from 2006 to 2011. PARTICIPANTS: Racially diverse mothers (N = 231) and their preterm infants born weighing less than 1,750 g. METHODS: Mothers and their infants were enrolled once the infants were no longer critically ill, weighed at least 1,000 g, and could be safely held outside the incubator by parents. Participants were instructed by study nurses; those allocated to the KC or ATVV groups were asked to engage in these interactions with their infants for a minimum of 3 times a week in the hospital and at home until their infants reached age 2 months adjusted for prematurity. RESULTS: Feeding at the breast during hospitalization, the duration of postdischarge breastfeeding, and breastfeeding exclusivity after hospital discharge did not differ statistically among the treatment groups. Regardless of group assignment, married, older, and more educated women were more likely to feed at the breast during hospitalization. Mothers who practiced KC, regardless of randomly allocated group, were more likely to provide their milk than those who did not practice KC. Breastfeeding duration was greatest among more educated women. CONCLUSION: As implemented in this study, assignment to the KC group did not appear to influence the measured breastfeeding outcomes. PMID- 26815800 TI - Effectiveness of a Breastfeeding Intervention on Knowledge and Attitudes Among High School Students in Taiwan. AB - OBJECTIVE: To evaluate the effectiveness of an educational intervention on the breastfeeding knowledge and attitudes of female high school students living in Taiwan. DESIGN: A prospective, two-group, quasi-experimental, repeated measure design. SETTING: A high school in Taichung, Taiwan. PARTICIPANTS: Two hundred four female high school students. METHODS: Data were collected through a self administered questionnaire at baseline, after the intervention, and 1 month later. After administration of the questionnaire at baseline, the experimental group (n = 103) received a 30-minute breastfeeding education; the control group (n = 101) did not. RESULTS: Findings showed that students in the experimental group had significantly greater breastfeeding knowledge immediately after the intervention and at 1 month postintervention. Also, compared with the control group, the experimental group had significantly greater positive breastfeeding attitudes after the intervention period, and the effect lasted at least 1 month. CONCLUSIONS: Breastfeeding interventions in schools improve adolescents' knowledge and attitudes. School nurses are well positioned to promote breastfeeding as a healthy lifestyle behavior within the school setting. PMID- 26815801 TI - Consumption of the Placenta in the Postpartum Period. AB - Postpartum women are consuming their placentas to achieve claimed health benefits, including improved mood, energy, and lactation. Strong scientific evidence to substantiate these claims is lacking. Self-reported benefits from some women include improved mood and lactation; animal models suggest there may be an analgesic effect. Possible risks include infection, thromboembolism from estrogens in placental tissue, and accumulation of environmental toxins. Women's health care providers should be aware of this practice to help women make informed decisions. PMID- 26815802 TI - Current Resources for Evidence-Based Practice, January/February 2016. PMID- 26815803 TI - Advancing the Care of Individuals and Couples at Risk for and Diagnosed With Infertility. PMID- 26815804 TI - Evidence-Based Care for Couples With Infertility. AB - When couples cannot achieve pregnancy, they often seek health care from medical and nursing specialists. The care the couple receives begins with a thorough assessment to determine the possible cause of infertility and to plan appropriate care to ensure the best chance for the couple to have a biological child. In this article, we provide an overview of the etiology and evaluation of infertility, the various treatment options available, and the appropriate clinical implications. PMID- 26815805 TI - Evidence-Based Management of Infertility in Women With Polycystic Ovary Syndrome. AB - Polycystic ovary syndrome (PCOS) is a polygenic disorder with a variable phenotype that commonly affects women of reproductive age. It can significantly affect a woman's ability to conceive and her quality of life. Effective treatment includes a multidisciplinary team approach that addresses the physiological and psychosocial manifestations of the disorder. Nurses have an important role in promoting early detection, education, and identification of services and resources to improve a woman's fertility and lifelong health. PMID- 26815806 TI - Reasons Why Young Women Accept or Decline Fertility Preservation After Cancer Diagnosis. AB - OBJECTIVE: To understand young women's reasons for accepting or declining fertility preservation after cancer diagnosis to aid in the development of theory regarding decision making in this context. DESIGN: Qualitative descriptive. SETTING: Participants' homes or other private location. PARTICIPANTS: Twenty seven young women (mean age, 29 years) diagnosed with cancer and eligible for fertility preservation. METHODS: Recruitment was conducted via the Internet and in fertility centers. Participants completed demographic questionnaires and in depth semi-structured interviews. Tenets of grounded theory guided an inductive and deductive analysis. RESULTS: Young women's reasons for deciding whether to undergo fertility preservation were linked to four theoretical dimensions: Cognitive Appraisals, Emotional Responses, Moral Judgments, and Decision Partners. Women who declined fertility preservation described more reasons in the Cognitive Appraisals dimension, including financial cost and human risks, than women who accepted. In the Emotional Responses dimension, most women who accepted fertility preservation reported a strong desire for biological motherhood, whereas women who declined tended to report a strong desire for surviving cancer. Three participants who declined reported reasons linked to the Moral Judgments dimension, and most participants were influenced by Decision Partners, including husbands, boyfriends, parents, and clinicians. CONCLUSION: The primary reason on which many but not all participants based decisions related to fertility preservation was whether the immediate emphasis of care should be placed on surviving cancer or securing options for future biological motherhood. Nurses and other clinicians should base education and counseling on the four theoretical dimensions to effectively support young women with cancer. PMID- 26815807 TI - AWHONN Position Statement. Newborn Screening. AB - The Association of Women's Health, Obstetric and Neonatal Nurses (AWHONN) supports national minimum standards for newborn screening (NBS) programs. Federal oversight is necessary to guarantee that all pregnant women have access to appropriate counseling and that their newborns have access to timely identification of and interventions for congenital and other disorders identified through routine screening. PMID- 26815809 TI - Focus on Solid Organ Injury. PMID- 26815808 TI - AWHONN Position Statement. The Role of Unlicensed Assistive Personnel (Nursing Assistive Personnel) in the Care of Women and Newborns. AB - The Association of Women's Health, Obstetric and Neonatal Nurses (AWHONN) recognizes that unlicensed assistive personnel (UAP) also known as nursing assistive personnel (NAP) can function as supportive members of the health care team under the direction of the professional registered nurse (AWHONN, 2010). The professional registered nurse is ultimately responsible for the coordination and delivery of nursing care to women and newborns. PMID- 26815810 TI - Cardiac and Pulmonary Injury. AB - Cardiac and pulmonary injuries present major challenges in diagnosis and treatment. Distinct differences between penetrating and blunt trauma of these organs exist. Outcomes for severe injuries are still grave. Organized trauma systems can provide optimal care by minimizing prehospital time, allowing easy access to imaging modalities, and offering state-of-the-art treatment strategies. A multidisciplinary approach, including surgeons, intensivists, and others, is absolutely necessary. PMID- 26815811 TI - Hepatic Trauma. AB - Hepatic injuries are one of the most common abdominal injuries following either blunt or penetrating trauma. CT scanning has revolutionized the treatment algorithm for these patients. The majority of patients are successfully treated with nonoperative management, but surgeons should have a clear understanding of the indications for operative intervention. An array of techniques including operative, interventional, and endoscopic, are often required for management of advanced grade hepatic injuries. PMID- 26815812 TI - Injuries to the Spleen. AB - BACKGROUND: Intra-abdominal organs, most commonly the spleen and liver, are injured in 40-50% of polytraumatized patients. Because of its important immunological functions, preservation of the injured spleen is of paramount importance. METHODS: There are both conservative and surgical approaches to preservation of the spleen in trauma cases. Of the techniques available for this purpose, tissue adhesives, coagulation, partial resection, and mesh splenorrhapy are the most suitable. RESULTS: Nonoperative management is a worthwhile option in hemodynamically stable patients. The decisive factor for successful conservative management is the degree of injury. We find that the manner in which heparin is administered plays an important role. Tissue adhesives are commonly used with good success with superficial lacerations. Coagulation techniques are also suitable for organ conservation with grade I and II injuries. Splenorraphy with resorbablemesh is the method of choice with the deep lacerations as it permits rapid and permanenthemostasis. If an injury only involves one pole or one half of the spleen, resection of that part of the organ is an option. Partial resection with a stapler is advisable for speed and effectiveness. Total fragmentation or separation of the hilus is treated with an immediate splenectomy, saving the tail of the pancreas. CONCLUSION: In trauma cases, every attempt should be made to save the spleen. If splenectomy cannot be avoided, the splenectomized patient should be immunized against pneumococcus and be informed of his/ her resultant immune deficiency. PMID- 26815813 TI - Injuries to the Pancreaticoduodenal Complex. AB - Injuries to the pancreaticoduodenal complex present a significant challenge both in diagnosis and management. The retroperitoneal location of the pancreas means that it is not a common site of injury, but this also contributes to the difficulty in diagnosis, as the organ is concealed, and investigation often results in delay with its attendant increase in morbidity. The increase in violence in society, particularly of penetrating injuries and the increase in energy of wounding from gunshots, has made pancreatic injury more common. In many cases the surgical management is relatively simple, but occasionally complex and technical surgical solutions are necessary and the position of the pancreas makes its access and all procedures on it challenging. To compound this, pancreatic trauma is associated with a high incidence of injury to adjoining organs and major vascular structures, which adds to the high morbidity and mortality, and complications occur in 30-60% of patients [1, 2]. PMID- 26815814 TI - Postinjury Primary Abdominal Compartment Syndrome. AB - Postinjury abdominal compartment syndrome (ACS) has evolved during the 1980s together with the introduction of damage control surgery (DCS) principles. DCS made it possible to salvage severely injured trauma patients who previously would have exsanguinated due to uncontrollable coagulopathic bleeding. These patients had severe hemorrhagic shock; their abdomens were tightly packed and had ongoing massive resuscitation. ACS is a lethal complication of the damage control patients. For today the pathophysiological characteristics of ACS are described, the intra-abdominal pressure is measured on many intensive care units. Postinjury ACS (primary and secondary) is one of the better characterized etiological types of ACS: risk factors, diagnostic criteria, independent predictors and preventive strategies are all well documented. Since the mortality of full-blown postinjury ACS is still unacceptably high and does not seem to improve with earlier decompression, prevention is the recommended strategy to decrease the morbidity and mortality. Open abdomen is one of the important preventive strategies but it is not free from morbidity and mortality. With aggressive open abdomen management in postinjury ACS these complications can be minimized. More importantly, timely hemorrhage control and hemostatic resuscitation are the likely solutions for more efficient prevention of the postinjury ACS. PMID- 26815815 TI - Displaced Operable Radial Head Fractures : Functional Outcome Correlations. AB - BACKGROUND: Radial head fractures are common injuries occurring in conjunction with other injuries. We hypothesize that the associated injuries are under diagnosed, under-treated and are under-estimated in terms of their relevance to the patients final functional outcome. We hypothesize a high correlation between the associated injuries and poor functional scores. MATERIALS: Thirty-nine displaced radial head fractures were clinically, radiologically and functionally assessed at an average of 47 months postoperatively. Demographic data, case notes, and follow up data were statistically analyzed. Pearson's correlation coefficient was performed for the associated injuries and final functional scores. RESULTS: There were 21 type II and 18 type III radial head fractures. About 52% of Mason type II (11/21) and 94% of the Mason type III (17/18) had associated injuries. The average Mayo Elbow Performance Score for the Mason II fractures was 70 and for the Mason III was 55. There was a strong correlation between the number of associated injuries and functional scores. For Mason II injuries the Pearson correlation coefficient was r = -0.994, and for the Mason III group, r = -0.972. CONCLUSIONS: "Isolated radial head fractures" are rare. All displaced radial head fractures need thorough clinical and radiographic evaluation. The associated injuries are often unappreciated on initial diagnosis and are often under-treated. Associated injuries are strongly correlated with poor functional scores and therefore need to be addressed during surgery. PMID- 26815816 TI - Midfacial Fractures: A Scoring Method and Validation on 117 Patients. AB - The midfacial region (MR) is located in the middle-third of the face, composed of several bones and surrounded by complex anatomical structures so that MR fractures (MRFs) often involve other parts of the face. A staging system for classifying MRFs is of paramount importance in order to exchange information among trauma centers. Le Fort described three lines of fractures but still there is no scoring method to stage MRFs. In this article, a classification for MRFs is proposed. It is based on Le Fort's three lines and it defines seven facial units. MRFs can be staged as follows: F in situ = a fracture line without fragment mobility (i.e. greensticked); F1 = a fracture involving one MR unit (MRU); F2 = a fracture involving two MRUs; F3 = a fracture involving three MRUs; F4 = a fracture involving four or more MRUs or neighboring anatomical regions (i.e. mandible, orbit and skull). To evaluate the suitability of the proposed classification a retrospective study on a series of 117 MRFs was performed. Age, gender, new stage, clinical diagnosis at admission, type of surgery, and outcome were considered. A good correlation between the proposed classification and the studied variables was detected. In conclusion, the proposed classification is a simple and precise method of staging MRFs. It can summarize MRFs and be used in daily practice. It is our understanding, however, that a multi-centers study should be performed before the effectiveness of the proposed classification can be clearly stated. PMID- 26815817 TI - Severe Fracture of the Tibial Pilon: Results with a Multidirectional Self-locking Osteosynthesis Plate Utilizing a Two-stage Procedure. AB - The objective of this study is to determine the treatment result of severe fractures of the tibial pilon using a two-stage treatment plan with a singular implant type. The setting is a level 1 trauma centre, the design a consecutive series of patients with a retrospective data evaluation. Due to anatomical circumstances, soft-tissue treatment is extremely important for fractures of the tibial plafond. After promising results reported about a two-staged treatment plan with external fixation and secondary internal fixation, we incorporated this method in our treatment protocol. This consisted in a second stage of internal fixation with a specifically developed locked pilon plate with multi-directional applicable screws. Between March 2000 and February 2005, 42 patients with high energy fractures of the tibial plafond were treated using a two-staged treatment plan: firstly the fracture was stabilized with an external fixator immobilizing the ankle joint. Secondly, after stabilization of the soft-tissue situation (mean 9.2 days) open reduction and internal fixation with a locked-screw plate was performed. Complications experienced included three cases of superficial wound necrosis, in two cases a deep vein thrombosis occurred. All fractures healed but two patients needed an early bone graft because of insufficient bony consolidation. At follow-up, six Patients had no deficit in the range of movement of the ankle compared with the unaffected side, 19 patients experienced a deficit of movement of less then one third compared to the opposite side. In 27 cases no or only mild posttraumatic arthritis of the ankle occurred. There was no secondary loss of reduction or need for arthrodesis. The mean AOFAS score was 73.4 (52-97). A two-stage treatment plan in fractures of the distal lower limb with external fixation followed by locked-plate osteosynthesis reduces local complications with a good functional result. PMID- 26815818 TI - The use of Hypertonic Saline in the Treatment of Post-Traumatic Cerebral Edema: A Review. AB - Effective methods for treating cerebral edema have recently become a matter of both extensive research and significant debate within the neurosurgery and trauma surgery communities. The pathophysiologic progression and outcome of different forms of cerebral edema associated with traumatic brain injury have yet to be fully elucidated. There are heterogeneous factors influencing the onset and progress of post-traumatic cerebral edema, including the magnitude and type of head injury, age, co-morbid conditions of the patient, the critical window for therapeutic intervention and the presence of secondary insults including hypoxia, hypotension, hypo/hyperthermia, degree of raised intracranial pressure (ICP), and disruption of blood brain barrier (BBB) integrity. Although numerous studies have been designed to improve our understanding of the etiology of post-traumatic cerebral edema, therapeutic interventions have traditionally been focused on minimizing secondary insults especially raised ICP and improving cerebral perfusion pressure. More recently, fluid resuscitation strategies using hyperosmolar agents such as pentastarch and hypertonic saline (HS) have achieved some success. HS treatment is of particular interest due to its apparent advantageous action over other types of hyper-osmotic solutions in both clinical and laboratory studies. In this review, we provide a summary of recent literature concerning the pathogenesis and mechanisms involved in the various types of cerebral edema, and the possible mechanisms of action of HS for the treatment cerebral edema. PMID- 26815819 TI - Tracheal Rupture After Blunt Trauma. AB - Tracheal injuries are uncommon after blunt trauma. Early diagnosis and urgent treatment are primordial to reduce both mortality and morbidity. We describe the case of a 45-year-old man who met with a traffic accident and was brought to the emergency department. Progressively, he developed dyspnoea and coughing. The diagnosis of a tracheal rupture was established and the rupture was closed surgically. The management of the patient with suspected tracheal rupture is discussed. PMID- 26815820 TI - Popliteal A-V Fistula with Pseudo-aneurysm: A Complication Following Total Knee Arthroplasty. AB - Arthroscopy and total knee replacement (TKR) are the two orthopedic procedures in which instruments are routinely placed near the posterior capsule of the knee. A review of the literature demonstrated that the four commonest reported problems following TKR are thrombosis, arterial transection, A-V fistula, and aneurysm formation. Reports on popliteal artery injury with severe patient morbidity following arthroscopy and TKR have been described in the literature. Despite the uncommon occurrence of these injuries, the outcome can be devastating, leading to further surgery, including vascular repair or possibly even amputation of the affected limb. We present a rare case of popliteal A-V fistula following TKR and discuss the probable etiology and the management. PMID- 26815821 TI - Traumatic First Metatarsal Bone Loss Treated with a Staged Method Using an Antibiotic Cement Spacer and Subsequent Autografting: A Case Report. AB - Fractures with bone loss are rare. A staged method of using bone cement as a spacer and subsequent autografting has been used successfully to treat traumatic bone loss of long bones. We report a case of traumatic bone loss of the 1st metatarsal bone that was treated successively with a staged method of using antibiotic-impregnated bone cement as a spacer in the primary phase and cancellous autografting in second-stage surgery. PMID- 26815822 TI - Introduction to the fourth "Focus-on" issue devoted to Disaster and Military Surgery in EJTES. PMID- 26815823 TI - Overview of polytrauma patients in the first 10 days after the Sichuan earthquake: a report from the No. 903 Military Hospital, Jiangyou. AB - PURPOSE: The purpose of this study was to investigate the profile of traumas, the severity, and mortality of polytrauma patients in a front-line hospital after the 2008 Sichuan earthquake. METHODS: Patients who had two or more injuries to physical regions or organ systems, where at least one injury or the combination of injuries carried a certain risk of fatal outcome, with Injury Severity Score (ISS) >=16, were considered as polytrauma patients and included in this study. Medical records consisting of demographic data, distribution and type of injuries, Abbreviated Injury Scale (AIS) score of each injury, ISS, surgical procedures, mortality rate, and features of the deaths were collected and analyzed. RESULTS: A total of 70 earthquake-related polytrauma patients were treated in our hospital during the first 10 days after the earthquake. The mean ISS of these patients was 26.9, and 77.1% of these patients were critically injured (ISS >= 25). Among the 224 injuries, the most common injury site was the extremities (30.8%), 81.2% of which were fractures. A total of 152 surgical procedures were performed on these patients, of which orthopedic procedures accounted for 85.5%. During the first 10 days, 21 patients with significantly higher ISS than the survivors died in the hospital. CONCLUSIONS: The mortality rate of the polytrauma patients in this rescue operation was high. The ISS was a feasible tool to estimate the severity of polytrauma patients. Specialists in orthopedics, critical care, and respiratory disorders were in great demand during the management of these patients in such conditions. PMID- 26815824 TI - Indications for bullet removal: overview of the literature, and clinical practice guidelines for European trauma surgeons. AB - PURPOSE: The incidence of gunshot wounds from civilian firearms is increasing. Despite this fact, guidelines on indications for bullet removal are scarce. In this analysis, we combine an overview of the available literature in these rare entities with our experiences in our own clinical practices. METHODS: We conducted a systematic literature search of computerized bibliographic databases (Medline, EMBASE, and the Cochrane Central Register). The local experience of the authors was reviewed in light of the available literature. RESULTS: 145 full-text articles were suitable for further evaluation. Only six retrospective studies were available, and no prospective study could be retrieved. Most of the articles were case reports. In the South African co-author's own clinical practice, approximately 800 patients are treated per year with gunshot wounds. CONCLUSIONS: In summary, there are only a few clear indications for bullet removal. These include bullets found in joints, CSF, or the globe of the eye. Fragments leading to impingement on a nerve or a nerve root, and bullets lying within the lumen of a vessel, resulting in a risk of ischemia or embolization, should be removed. Rare indications are lead poisoning caused by a fragment, and removal that is required for a medico-legal examination. In all other cases the indication should be critically reviewed. PMID- 26815825 TI - Contemporary body armor: technical data, injuries, and limits. AB - The introduction of firearms in the fifteenth century led to the continuous development of bulletproof personal protection. Due to recent industrial progress and the emergence of a new generation of ballistic fibers in the 1960s, the ability of individual ballistic protections to stop projectiles greatly increased. While protective equipment is able to stop increasingly powerful missiles, deformation during the impact can cause potentially lethal nonpenetrating injuries that are grouped under the generic term of behind armor blunt trauma, and the scope and consequences of these are still unclear. This review first summarizes current technical data for modern bulletproof vests, the materials used in them, and the stopping mechanisms they employ. Then it describes recent research into the specific ballistic injury patterns of soldiers wearing body armor, focusing on behind-armor blunt trauma. PMID- 26815826 TI - Causes of inpatient death for patients with warfare-related limb trauma and logistic regression analysis of the risk factors. AB - OBJECTIVES: To explore the causes and risk factors of inpatient death for patients with warfare-related limb trauma. METHODS: A retrospective study involving 339 patients with warfare-related limb trauma who were admitted to our hospital from 1998 to 2002 was conducted. Autopsy was performed for 15 cases who died in order to investigate the cause of death. Furthermore, based on the clinical features of warfare-related trauma patients, 11 factors were selected for further analysis: X1: causes of trauma, X2: shock after injury, X3: time from injury to hospital admission, X4: injured sites, X5: combined trauma (including head, thorax, abdomen, and vascular injury), X6: number of surgical procedures, X7: foreign body remaining, X8: fracture, X9: amputation, X10: duration of tourniquet homeostasis, X11: infection. All variables were available in all cases, and all parameters were quantified and fed into a computer. Multivariate statistical analysis was performed with a logistic regression model to elucidate the risk factors influencing death. RESULTS: Fifteen of the 339 inpatient cases died (4.4%). The causes were primarily acute renal failure (ARF) (seven cases, 46.7%), pulmonary embolism (PE) (three cases, 20.0%), multiple organ system failure (MOSF) (two cases, 13.3%), and gas gangrene (three cases, 20.0%). There was one case of gas gangrene with concomitant ARF, and one of gas gangrene with MOSF. The primary risk factors influencing death included shock, amputation, and complicating infection (P < 0.05). CONCLUSION: The primary cause of death from warfare-related limb trauma is ARF. The appropriate and prompt management of shock patients, the correct timing of amputation, and the prevention and correct handling of infection are important in reducing mortality. PMID- 26815827 TI - Assessment of hospital disaster plans for conventional mass casualty incidents following terrorist explosions using a live exercise based upon the real data of actual patients. AB - PURPOSE: The National Committee for Hospital Preparedness for Conventional Mass Casualty Incidents and the Hospital Preparedness Division of the Home Front Command are in charge of preparing live exercises held yearly in public hospitals in Israel. Our experience is that live exercises are limited in their ability to test clinical decision making and its influence upon incident management. A live exercise was designed upon real patient data and tested in several public hospitals. The aim of the manuscript is to describe the impact of this new format on clinical decision making in large-scale live exercises. METHODS: A database of histories, physical examination findings, laboratory results and imaging results for 420 patients treated following terrorist explosions was created using information derived from actual patient encounters. Similar information for 100 patients treated following motor vehicle accidents was also collected. Information from the database was used to create victim profiles used during the course of exercises held in eight public hospitals with 60-800-bed capacities. RESULTS: Before implementing the new injury tags, no conclusions could be made concerning the quality of clinical decision making. Conducting the exercise using the new format helped identify deficiencies in the hospital disaster plan in triage, emergency department management and in the proper utilisation of resources such as radiology, operating rooms and the secondary transfer of patients. CONCLUSION: Previous knowledge of patient diagnoses and resource needs allow the identification and quantification of deficiencies and problems identified in clinical decision making, resource utilisation and incident management. PMID- 26815828 TI - Injury pattern of suicide bomb attacks in Pakistan. AB - PURPOSE: The aim of our study was to analyze the pattern of injuries, hospital care, and outcome of the victims of suicide bomb attacks in Pakistan. METHODS: This prospective, cohort study was conducted at the Combined Military Hospital Rawalpindi during the last 3 years. Seriously injured patients in the "immediate category" were resuscitated in the emergency operation theater adjacent to the emergency room and, after resuscitation, the patients were transferred to the main operation theaters, where consultant surgeons were available. RESULTS: During the study period, 1,296 terrorist victims presented to the emergency department and (86.9%) were admitted, with a mean hospital stay of 8.2 +/- 2.1 days. The majority of patients arrived by ambulance (91%) and only 38 (3%) were evacuated by air. Penetrating splinter injuries were the most prevalent (87%), and 29% patients also had associated injuries. Open bone fractures were found in 48% and 42% had injured hollow and solid viscous. Overall, 33% of patients had thoracic injuries and neuro-trauma was observed in 16% of the study population. Deafness was a feature in 33% patients, 121 had to undergo limb amputations, and mortality remained in 7% of patients. CONCLUSION: Most of the problems encountered were logistic in nature. Early evacuation of the victims remains pivotal in saving lives. The major causes of death in peripheral patients was hypovolemic shock, sepsis, and hypothermia. Mortality and morbidity can be enhanced by ample fluid resuscitation, tetanus prophylaxis, and proficient first aid at the site of injury. PMID- 26815829 TI - Clinical review: Volkmann's ischaemic contracture. AB - INTRODUCTION: Volkmann's ischaemic contracture is a devastating condition with serious motor and sensory functional implications for the affected limb. This clinical review outlines acute compartment syndrome and Volkmann's ischaemic contracture, their presentation, evolution and current management. AIMS: This up to-date clinical review is aimed at both specialist and non-specialist healthcare professionals who can play a key role in the early recognition of signs and symptoms to allow prevention of the condition. METHODS: No Cochrane reviews are currently available regarding Volkmann's ischaemic contracture. Medline, EMBASE and Scopus databases were searched using the MeSH terms 'Volkmann's ischaemic/ischemic contracture' and 'compartment syndrome'. Current guidelines were referred to. DISCUSSION: Prevention is essential regarding Volkmann's ischaemic contracture. This can be achieved through careful observation of patients sustaining high-risk extremity injuries, notably, children with supracondylar fractures of the humerus, and immediate decompression if signs and symptoms of a compartment syndrome are present. Increased awareness amongst doctors of compartment syndrome is fundamental and will allow early recognition, clinical diagnosis and subsequent fasciotomy. PMID- 26815830 TI - Delays in diagnosis in early trauma care: evaluation of diagnostic efficiency and circumstances of delay. AB - BACKGROUND: Trauma centers, trauma management concepts, damage control surgery and the integration of whole-body CT scanning into early trauma care have reduced mortality in traumatized patients significantly. However, some injuries are still initially missed. In this study, the diagnostic efficiency of early trauma care and the circumstances of delays in diagnosis were evaluated. MATERIALS AND METHODS: Initially missed diagnoses in 111 traumatized patients were recorded retrospectively. "Primary diagnoses" after the emergency room (ER) phase including CT scanning with immediate data evaluation were compared to "secondary diagnoses" after a secondary survey of the CT data, as well as to discharge diagnoses. Circumstances of delay were assessed according to injury severity score (ISS), hospital admission, mechanism of injury, diagnostics, treatment, time in the intensive care unit, hospitalization and mortality. RESULTS: 73% of the patients arrived at the ER during on-call hours. In 23% of all patients, diagnoses were missed after the ER phase, while in 12% of the patients diagnoses were missed after the secondary survey of the CT data. One half of the missed diagnoses were almost impossible to detect; the other half were judged to be acceptable. During on-call hours, 9% more patients with delays in diagnosis were observed. Injury severity in patients with delays in diagnosis was significantly higher than in patients without. CONCLUSIONS: Although diagnostic quality in early trauma care has improved, some diagnoses are initially missed. Severely injured patients with life-threatening or potentially life-threatening injuries arriving at the ER during on-call hours were at higher risk for delays in diagnosis. A secondary evaluation of acquired CT data and repetitive examinations are essential. PMID- 26815831 TI - Emergency thoracotomies in the largest trauma center in Denmark: 10 years' experience. AB - AIM: The aim of our study was to investigate the outcome in terms of 30-day survival and to determine whether preoperative factors could predict the outcome. METHODS: All patients who underwent an emergency thoracotomy (ET) during the period 2000 to 2009 were included. The patients were divided into two groups: emergency department thoracotomy and operating room thoracotomy. Data on demographics, mechanism of injury, intraoperative data, Injury Severity Scores (ISS), probability of survival, signs of life, transportation time, indications, and outcome were collected. RESULTS: Forty-four ETs were performed. The mechanisms of injury were penetrating in 28 (64%) and blunt in 16 (36%) cases. In the emergency department thoracotomy group, the survival was 45 versus 20% for penetrating and blunt trauma, respectively. The total survival was 33%. In the operating room thoracotomy group, the survival was 83%. The survivors had a significantly lower ISS and a higher calculated probability of survival. The calculated mean probability of survival was 44 and 84% in the emergency department thoracotomy and operating room thoracotomy groups, respectively. The actual survival was similar, with 33% in the emergency department thoracotomy group and 83% in the operating room thoracotomy group. CONCLUSIONS: The probability of survival and ISS are good predictors of survival in these patients and should be included in the future in order to make upcoming studies easier to compare. Patients with very high ISS or low probability of survival survived, justifying the procedure in our center. PMID- 26815832 TI - What are the predictors of scapula fractures in high-impact blunt trauma patients and why do we miss them in the emergency department? AB - AIM: To find out the predictors of scapula fractures in high-impact blunt trauma patients and the predictors of missing them in the emergency department (ED). METHODS: This is a retrospective descriptive review of patients treated at a single hospital over a 3.5-year period. The study included 1,039 high-impact blunt trauma patients of any age. The patients were divided into two groups: patients with scapula fractures (the patient group) and others (the control group). The patient group was re-assessed into two subgroups: patients with and without missed scapula fractures. Logistic regression analysis was used to assess the predictors of a scapular fracture in the ED. RESULTS: The incidence of scapula fractures was 4%. The Injury Severity Scores (ISS) of the scapula fracture group were significantly higher than those of the control group (P < 0.0001). Patients with scapula fractures were significantly older (P < 0.001). Patients with scapular body fractures stayed for significantly longer in the intensive care unit (ICU) (P = 0.039) and their mean Abbreviated Injury Scale (AIS)face score was higher (P = 0.04) compared to scapular fractures without body parts. Scapula fractures were missed in 35.7% of patients. All bilateral scapula fractures were missed. Computerized tomography showing shoulder region or scapula was obtained in 26.7% of missed injuries. CONCLUSION: After matching for ISS, the mortality of patients with scapula fracture was significantly higher than the control group. We observed that fractures in the glenoid and scapular neck occurred higher than in the body region. We found that the seniority of the ED doctor, consultation ratio for orthopedics in ED, and the existence of brain contusion were important parameters for missing scapula fractures in ED. PMID- 26815833 TI - Severe pelvic fracture-related bleeding in pediatric patients: does it occur? AB - PURPOSE: Pediatric pelvic fractures are rare and less likely to cause hemodynamic instability than similar injuries in adult patients. The associated injuries are common, and they have a major impact on mortality. The aim of the present study was to evaluate the risk of life-threatening hemorrhage associated with unstable pelvic fractures in children. METHODS: We identified retrospectively all pediatric pelvic fractures (ring and acetabulum) treated at Helsinki University Central Hospital during a 10-year period (1998-2007). Stable A-type fractures (fractures not involving the pelvic ring) were excluded. All available pre- and in-hospital medical records were reviewed. The collected data consisted of patient characteristics, mechanisms of injury, vital signs, laboratory tests, care given, other injuries diagnosed, and the 30-day survival rate. RESULTS: There were 71 (40 males) pediatric patients (median age 14, range 1-16 years) with unstable pelvic fractures; 66 pelvic ring and 5 acetabulum fractures. The most common mechanism of injury was traffic accident (69%). Four patients had life-threatening bleeding. All had fracture of a mature pelvic ring, but the source of massive bleeding was pelvic ring fracture in only two patients (2.8% of all patients). No acetabulum fracture-related major pelvic bleeding was observed. One patient (age 16 years) required emergency surgery and angioembolization for pelvic bleeding. No life-threatening pelvic bleeding was seen among patients with immature bony pelvis. Pelvic ring fractures were surgically treated in 25 patients. Two patients died from head injuries (overall mortality 2.8%), but there were no bleeding-related deaths. CONCLUSIONS: We conclude that life threatening bleeding from pelvic or acetabular fractures in pediatric patients is rare (2.8%), and does not contribute to the overall mortality. PMID- 26815834 TI - Prehospital HMG Co-A reductase inhibitor use and reduced mortality in hemorrhagic shock due to trauma. AB - INTRODUCTION: 3-Hydroxy-3-methyl-glutaryl Co-A reductase inhibitors (HMG Co-A reductase inhibitors, statins) are commonly used medications for the control of serum cholesterol. Recent data suggests that these medications also modify the inflammatory pathways in sepsis, septic shock, and hemorrhagic shock due to ruptured abdominal aortic aneurysms. Statin use in hemorrhagic shock due to trauma, however, has conflicting data, with one study showing improvement, but only in certain subsets of patients. STUDY DESIGN: We retrospectively reviewed the medical records of patients from our institution's trauma registry database from January 2000 to December 2008. We included patients with an age greater than 45 years and an Injury Severity Score (ISS) greater than 15 with evidence of shock as follows: hypotension, elevated serum lactate, base deficit, metabolic acidosis, or objective evidence of end-organ malperfusion. We excluded patients with devastating head injury, patients with pre-existing advance directives directing against life-sustaining measures, patients for whom family or health care proxies withdrew support in 24 h or less, and patients who succumbed to their injuries in the first 24 h in the hospital. We compared age, gender, mortality, statin use, aspirin use, and Sequential Organ Failure Assessment (SOFA) scores. RESULTS: Mortality in the group without prehospital statin use was 38.1% (95% confidence interval [CI]: 28.4-48.8%) and mortality in the group with prehospital statin use was 8.3% (95% CI: 2.13-22.5%, P = 0.0009). The absolute risk reduction was 29.8% and the relative risk reduction was 78.1%. Survivors were statistically significantly younger than nonsurvivors in the group without prehospital statin use, but not in the group with documented prehospital statin use. There was no similar benefit to aspirin use. There were no significant differences in the SOFA scores, hospital length of stay (HLOS), or intensive care unit length of stay (ICU LOS) between statin users and nonusers. CONCLUSIONS: Prehospital HMG Co-A reductase use was associated with improved survival in a population with severe trauma and evidence of ongoing hemorrhagic shock. PMID- 26815835 TI - Analysis of factors predicting success and failure of treatment after type B periprosthetic humeral fractures: a case series study. AB - PURPOSE: The purpose of this study was to investigate which factors predict the failure and success of treatment of periprosthetic type B humeral fractures that have occurred traumatically. METHODS: The institutional admission database and the trauma registry were retrospectively reviewed. A total of 8 patients suffering from periprosthetic humeral fractures were included. The time span was 10 years (2000-2010). RESULTS: The average age at the time of the fracture was 77 years. Surgery was performed at an average of 5.6 days after injury. In three patients with a well-fixed and one with an unstable humeral component, open reduction and internal fixation with the use of a plate and screws was performed. Two patients with a Delta prosthesis had an unstable humeral component. A proximal humeral resection and an implantation of an HMRS prosthesis was performed in one patient. The other patient received a Delta revision stem prosthesis, cable and plate fixation. Two patients were treated conservatively. CONCLUSIONS: Early surgical treatment with angular stable implants in fractures with a stable stem and replacement with a revision long-stem component in fractures with a loose prosthesis is recommended. Special attention should be paid to bone quality and anatomical proximity to the radial nerve. Conservative treatment of type B fractures is not sufficient to achieve union, especially in short oblique or transverse fractures. PMID- 26815837 TI - Message from the President. PMID- 26815838 TI - Tensile strains give rise to strong size effects for thermal conductivities of silicene, germanene and stanene. AB - Based on first principles calculations and self-consistent solution of the linearized Boltzmann-Peierls equation for phonon transport approach within a three-phonon scattering framework, we characterize lattice thermal conductivities k of freestanding silicene, germanene and stanene under different isotropic tensile strains and temperatures. We find a strong size dependence of k for silicene with tensile strain, i.e., divergent k with increasing system size; however, the intrinsic room temperature k for unstrained silicene converges with system size to 19.34 W m(-1) K(-1) at 178 nm. The room temperature k of strained silicene becomes as large as that of bulk silicon at 84 MUm, indicating the possibility of using strain in silicene to manipulate k for thermal management. The relative contribution to the intrinsic k from out-of-plane acoustic modes is largest for unstrained silicene, ~39% at room temperature. The single mode relaxation time approximation, which works reasonably well for bulk silicon, fails to appropriately describe phonon thermal transport in silicene, germanene and stanene within the temperature range considered. For large samples of silicene, k increases with tensile strain, peaks at ~7% strain and then decreases with further strain. In germanene and stanene, increasing strain hardens and stabilizes long wavelength out-of-plane acoustic phonons, and leads to similar k behaviors to those of silicene. These findings further our understanding of phonon dynamics in group-IV buckled monolayers and may guide transfer and fabrication techniques for these freestanding samples and engineering of k by size and strain for applications of thermal management and thermoelectricity. PMID- 26815836 TI - Do stable multiply injured patients with bilateral femur fractures have higher complication rates? An investigation by the EPOFF study group. AB - BACKGROUND: Polytrauma patients with bilateral femur shaft fractures are known to have a higher rate of complications when compared with those who have sustained unilateral fractures. The current study tests the hypothesis that the high incidence of posttraumatic complications in patients who do not have a severe head or chest injury is caused by accompanying injuries rather than by the additional femur fracture. METHODS: Inclusion criteria New Injury Severity Score > 16 points; AIS score value of the chest <=3 points and no severe head injury. Two study groups: a unilateral group (USF group) (n = 146) and a bilateral femur shaft fracture group (BSF group) (n = 19). Endpoints monitored were length of stay in the intensive care unit, duration on a ventilator, and several postsurgical complications (e.g., SEPSIS, acute lung injury). Statistics Fisher's exact test for binary variables, and independent t-tests and regression analyses for continuous indicators of injury severity and clinical outcomes. RESULTS: Patients with bilateral femur fractures had a significantly higher incidence of hemothorax. Moreover, they received blood transfusions more often upon admission, and exhibited a longer ICU stay (p = 0.008). However, this patient group did not exhibit a significantly higher incidence of postsurgical complications (p = 0.1) than those with unilateral fractures. After adjusting for injury severity, no difference in the length of the ICU stay was observed. Bilateral fracture patients who were in an uncertain condition preoperatively had a longer length of stay in the ICU postoperatively (p = 0.002). CONCLUSIONS: In the absence of major head or chest injuries, patients with multiple injuries and bilateral femur shaft fractures have a similar complication rate to polytrauma patients with unilateral fractures. Moreover, an uncertain condition preoperatively was associated with an increased stay in the intensive care unit. The results support the idea that associated injuries rather than the additional femur fracture are responsible for complications during the clinical stay. PMID- 26815839 TI - [Quo vadis, modern intensive care medicine? Outdated considerations regarding risks and side effects]. AB - Modern intensive care medicine is faced with large challenges which are not solely caused by medical-technical progress, but above all by the demographic and value-related changes of society and its citizens. Thereby, three central problem areas are of particular interest: the fragile effectiveness of a patient's right to self-determination at the end of life, the uncertainties regarding the demarcation of futility, and the question of the influence of economic considerations (rationing) in view of the different levels for the allocation of duties and execution of duties. This article contains the revised version of the lecture from June 18, 2015 on the occasion of the 47th annual joint conference of DGIIN (Deutschen Gesellschaft fur Internistische Intensivmedizin und Notfallmedizin) and OGIAIN (Osterreichischen Gesellschaft fur Internistische und Allgemeine Intensivmedizin und Notfallmedizin) on the general subject: "quality and humanity". PMID- 26815840 TI - [Analgesia in intensive care medicine]. AB - BACKGROUND: The administration of sedatives and analgesics on the intensive care unit (ICU) is routine daily practice. The correct discrimination between delirium, pain and anxiety or confusion is essential for the strategy and selection of medication. The correct pain therapy and sedation are essential for patient quality of life on the ICU and for the prognosis. OBJECTIVE: The aim of this article is to present state of the art recommendations on the classification of pain and pain therapy on the ICU. MATERIAL AND METHODS: An online search was carried out in PubMed for publications on the topics of "pain" and "ICU". RESULTS: Critical care patients are frequently subjected to many procedures and situations which can cause pain. The perception of pain is, among other things, influenced by the degree of orientation, anxiety and the degree of sedation. The administration of analgesics and non-pharmacological approaches are effective in reducing the stress perceived by patients. DISCUSSION: The main aim is improvement in the awareness of nursing and medical personnel for pain inducers and pain perception in ICU patients. The classification of pain must be made objectively. Therapeutic targets must be defined and in addition to the correct selection of pain medication, non-pharmacological approaches must also be consistently implemented. PMID- 26815841 TI - In situ atomic scale visualization of surface kinetics driven dynamics of oxide growth on a Ni-Cr surface. AB - We report the in situ atomic-scale visualization of the dynamic three-dimensional growth of NiO during the initial oxidation of Ni-10at%Cr using environmental transmission electron microscopy. A step-by-step adatom growth mechanism in 3D is observed and a change in the surface planes of growing oxide islands can be induced by local surface kinetic variations. PMID- 26815842 TI - Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke. AB - PURPOSE: Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. METHODS: Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. RESULTS: Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. CONCLUSIONS: Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger cerebral lesions associate with deeper vessel injury affecting vascular smooth muscle cells. PMID- 26815843 TI - Autonomic failure in Sjogren's syndrome. PMID- 26815844 TI - Advancing empirical resilience research. AB - We are delighted by the broad, intense, and fruitful discussion in reaction to our target article. A major point we take from the many comments is a prevailing feeling in the research community that we need significantly and urgently to advance resilience research, both by sharpening concepts and theories and by conducting empirical studies at a much larger scale and with a much more extended and sophisticated methodological arsenal than is the case currently. This advancement can be achieved only in a concerted international collaborative effort. In our response, we try to argue that an explicitly atheoretical, purely observational definition of resilience and a transdiagnostic, quantitative study framework can provide a suitable basis for empirically testing different competing resilience theories (sects. R1, R2, R6, R7). We are confident that it should be possible to unite resilience researchers from different schools, including from sociology and social psychology, behind such a pragmatic and theoretically neutral research strategy. In sections R3 to R5, we further specify and explain the positive appraisal style theory of resilience (PASTOR). We defend PASTOR as a comparatively parsimonious and translational theory that makes sufficiently concrete predictions to be evaluated empirically. PMID- 26815845 TI - Cgamma1 Deficiency Exacerbates Collagen-Induced Arthritis. AB - OBJECTIVE: IgG antibodies protect by aggregating pathogens and activating complement and stimulatory Fcgamma receptors (FcgammaR). Although IgG1 accounts for a large percentage of murine serum antibodies, it poorly activates complement, binds more avidly to inhibitory FcgammaRIIb than to stimulatory FcgammaRIII, and has a relatively low aggregating ability. We previously demonstrated that IgG1 protects against complement- and FcgammaR-independent renal disease by inhibiting immune complex obstruction of glomerular capillaries. The purpose of this study was to determine whether IgG1 also protects against the complement- and FcgammaR-dependent disorder, collagen-induced arthritis (CIA). METHODS: CIA was induced by injecting mice with type II collagen (CII) (active model) or with IgG2a and IgG2b anti-CII monoclonal antibodies (ArthritoMab) (passive model). Arthritis severity was assessed, and CII-specific IgG was titered. RESULTS: Cgamma1-deficient C57BL/6 mice lack IgG1 (IgG1(-/-) ); in these mice, arthritis developed at a higher frequency and was more severe compared with IgG1(+/+) mice in the active model. Disease was FcgammaRIII- and C3-dependent in both the IgG(+/+) and IgG(-/-) mouse strains and was not influenced by interleukin-4 receptor alpha in either strain. CII-specific IgG2a/c titers were considerably higher in IgG1(-/-) than in IgG1(+/+) mice and correlated with CIA incidence and severity. IgG1(+/+) mice that developed CIA had higher CII-specific IgG1 and IgG2a/c levels than did those without CIA. CII-inoculated BALB/c IgG1(+/+) and IgG1(-/-) mice had much lower CII-specific IgG2a/c titers than did C57BL/6 mice and failed to develop CIA but developed passive CIA when given ArthritoMab. CONCLUSION: The absence of a functional Cgamma1 gene indirectly promotes the development of CIA, likely through increased production of IgG2a/c, an isotype that strongly activates complement and stimulatory FcgammaR. PMID- 26815846 TI - [The language area of the brain: a functional reassessment]. AB - INTRODUCTION: During the late 19th and early 20th century, a 'brain language area' was proposed corresponding to the peri-Sylvian region of the left hemisphere as concluded by clinical observations. This point of view has continued up today. AIM: Departing from contemporary neuroimaging studies, to re analyze the location and extension the brain language area with regard to the different Brodmann areas. MATERIALS AND METHODS: Using the method known as metaanalytic connectivity modeling seven meta-analytic studies of fMRI activity during the performance of different language tasks are analyzed. RESULTS: It was observed that two major brain systems can be distinguished: lexical/semantic, related with the Wernicke's area, that includes a core Wernicke's area (recognition of words) and an extended Wernicke's area (word associations); and grammatical system (language production and grammar) corresponding to the Broca's complex in the frontal lobe, and extending subcortically It is proposed that the insula plays a coordinating role in interconnecting these two brain language systems. CONCLUSIONS: Contemporary neuroimaging studies suggest that the brain language are is notoriously more extended than it was assumed one century ago based on clinical observations. As it was assumed during the 19th century, the insula seemingly plays a critical role in language. PMID- 26815847 TI - [Inferior vertical nystagmus: is magnetic resonance imaging mandatory?]. AB - INTRODUCTION: The presentation of a down-beating nystagmus force to discard vascular pathology of brain and cervical joint with magnetic resonance imagine (MRI). Recent studies support the low profitability of this study and is subjected that this oculomotor sign has a peripheral origin especially when the patient has a benign paroxysmal positional vertigo (BPPV) with affection of the superior semicircular canal. AIM: To evidence the profitability of MRI in a population of patients with positional down-beating nystagmus. PATIENTS AND METHODS: We present a retrospective study with 42 consecutive patients. A complete clinical history and physical examination was performed. All of them perform vestibular tests (caloric and rotatory), cranial and cervical MRI. RESULTS: Fifty-two percent of patients present clinical manifestations and physical exploration compatible with BPPV. MRI was normal in 67%. We found spondylopathy in 26% and vascular cerebral pathology in 5%. Prevalence of type I Arnold-Chiari malformation was 9% in our population. None of them was founded when the main symptom was suggestive of BPPV. Results obtained of vestibular tests didn't contribute additional information to give an ethiologic diagnosis. CONCLUSION: The profitability of vestibular tests and MRI in our population with down beating nystagmus was very low. We must evaluate the real necessity of this test with the clinical context. PMID- 26815848 TI - [Prevalence of silent cerebrovascular lesions in patients with obstructive sleep apnea syndrome]. AB - INTRODUCTION: The obstructive sleep apnea syndrome (OSA) confers increased risk of cardiovascular disease, given its association with other vascular risk factors. Both OSA and other vascular risk factors are associated with silent brain lesions. AIM: To assess the prevalence of silent brain lesions in patients with OSA. PATIENTS AND METHODS: We retrospectively evaluated a cohort of 137 patients with OSA. The mean age was 65 +/- 12 years; 45% were women. The silent brain lesions in magnetic resonance imaging were assessed with the Visual Scale of Fazekas (FVS), and the presence of cortical infarcts, lacunar and microbleedings was assessed. RESULTS: Vascular risk factors prevalence was: hypertension 64%, dyslipemia 58%, diabetes 18%, smoking 34%, carotid atherosclerosis 26%, coronary heart disease 13%, and atrial fibrillation 4%. OSA was mild in 47%, moderate in 31% and severe in 22% of the patients. 91% of patients had periventricular hyperintensities, and 66% showed subcortical white matter lesions. The average value of apnea/hipopnea index was higher in patients with score 2 and 3 in FVS, although without statistical significance. CONCLUSIONS: Patients with OSA in our study have a high prevalence of silent brain lesions, mainly with microangiopathic pattern. This is possibly explained by the relation between OSA, hypertension and other vascular risk factors. PMID- 26815849 TI - [Myelopathy secondary to an aneurysmal bone cyst of thoracic spine]. AB - INTRODUCTION: Spinal aneurysmal bone cysts are very infrequent benign osteolytic lesions consisting of blood-filled cavities that are separated by osteo connective septa and osteoclast-type giant cells. Clinically they manifest with local pain, neurological symptoms secondary to spinal cord compression, and fractures, deformities and vertebral instability. We report a case of an aneurysmal bone cyst in the thoracic spine with neurological signs and symptoms treated by means of a full microsurgical resection, with no associated neurological sequelae. CASE REPORT: A 47-year-old woman, with no previous history of traumatic injuries, who was examined following several weeks with clinical signs and symptoms of paraesthesia in the lower limbs. Thoracic magnetic resonance imaging revealed the existence of a lytic lesion with clearly defined edges and marginal sclerosis in T4, in addition to involvement of the posterior vertebral elements and compression of the underlying spinal cord. The whole lesion was removed surgically, and the sensitive clinical symptoms disappeared after the procedure. The definite pathological diagnosis was spinal aneurysmal bone cyst. CONCLUSION: Despite their low incidence, aneurysmal bone cysts of the spine must be taken into account in the differential diagnosis of spinal bone tumours as a possible cause of subacute or chronic compressive myelopathy. Full surgical removal of the tumour is considered the preferred treatment, which is often curative and is associated with a good prognosis of the patient in the long term. PMID- 26815851 TI - [XXXVIII Annual Meeting of the Sociedad Andaluza de Neurologia. Communications]. PMID- 26815850 TI - [Optogenetics: its history, fundamentals and relevance in the present and the past]. AB - INTRODUCTION: Optogenetic is an experimental technique that combines genetic engineering and optical physics procedures to mark specific neurons in the brain and activate them at will through rays of light of certain frequency. AIM: To explain, to readers not versed in genetics the history, the rationale and the present and future applications of optogenetic in brain and mental processes research. DEVELOPMENT: The current development of this technique is allowing considerable advances in accurate knowledge about the neural circuits that control behavior and motivational and cognitive states, like hunger and thirst, pain, sleep or learning and memory. Among the first shocking results there are the creation and control of false memories. CONCLUSIONS: The optogenetics is a revolutionary experimental technique called to replace some of the classics techniques in brain behavior research and an important way in the development and control of mental processes and in the treatment of their diseases. PMID- 26815852 TI - [Tick-borne relapsing fever: an infrequent cause of meningitis]. PMID- 26815853 TI - [Sentinel headache in perimesencephalic subarachnoid hemorrhage]. PMID- 26815854 TI - [Tropical spastic paraparesis viewed from an Iberian context]. PMID- 26815855 TI - [Tropical spastic paraparesis viewed from an Iberian context. Reply]. PMID- 26815856 TI - Paternal kin recognition and infant care in white-faced capuchins (Cebus capucinus). AB - Evidence for paternal kin recognition and paternally biased behaviors is mixed among primates. We investigate whether infant handling behaviors exhibit paternal kin biases in wild white-faced capuchins monkeys (Cebus capucinus) by comparing interactions between infants and genetic sires, potential sires, siblings (full sibling, maternal, and paternal half-siblings) and unrelated handlers. We used a linear mixed model approach to analyze data collected on 21 focal infants from six groups in Sector Santa Rosa, Costa Rica. Our analyses suggest that the best predictor of adult and subadult male interactions with an infant is the male's dominance status, not his paternity status. We found that maternal siblings but not paternal siblings handled infants more than did unrelated individuals. We conclude that maternal but not paternal kinship influence patterns of infant handling in white-faced capuchins, regardless of whether or not they can recognize paternal kin. Am. J. Primatol. 78:659-668, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26815857 TI - Virulent Diuraphis noxia Aphids Over-Express Calcium Signaling Proteins to Overcome Defenses of Aphid-Resistant Wheat Plants. AB - The Russian wheat aphid, Diuraphis noxia, an invasive phytotoxic pest of wheat, Triticum aestivum, and barley, Hordeum vulgare, causes huge economic losses in Africa, South America, and North America. Most acceptable and ecologically beneficial aphid management strategies include selection and breeding of D. noxia resistant varieties, and numerous D. noxia resistance genes have been identified in T. aestivum and H. vulgare. North American D. noxia biotype 1 is avirulent to T. aestivum varieties possessing Dn4 or Dn7 genes, while biotype 2 is virulent to Dn4 and avirulent to Dn7. The current investigation utilized next-generation RNAseq technology to reveal that biotype 2 over expresses proteins involved in calcium signaling, which activates phosphoinositide (PI) metabolism. Calcium signaling proteins comprised 36% of all transcripts identified in the two D. noxia biotypes. Depending on plant resistance gene-aphid biotype interaction, additional transcript groups included those involved in tissue growth; defense and stress response; zinc ion and related cofactor binding; and apoptosis. Activation of enzymes involved in PI metabolism by D. noxia biotype 2 aphids allows depletion of plant calcium that normally blocks aphid feeding sites in phloem sieve elements and enables successful, continuous feeding on plants resistant to avirulent biotype 1. Inhibition of the key enzyme phospholipase C significantly reduced biotype 2 salivation into phloem and phloem sap ingestion. PMID- 26815858 TI - Formosins A-F: Diterpenoids with Anti-microbial Activities from Excoecaria formosana. AB - Three new halimane-type diterpenoids formosins A-C (1-3), and three clerodane type diterpenoids formosins D-F (4-6), were isolated from the twigs of Excoecaria formosana. Their structures were assigned on the basis of spectroscopic data analysis. Compounds 1 and 4 showed moderate anti-microbial activities against Bacillus subtilis (MIC = 50 and 50 MUg/mL, respectively). Compound 6 exhibited moderate anti-microbial activities against two strains of Helicobacter pylori (Hp SS1 and ATCC 43504) with MIC values of 50 and 50 MUg/mL, respectively. PMID- 26815860 TI - Focus on Midfoot Injuries. PMID- 26815859 TI - A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease. AB - Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines. PMID- 26815861 TI - Treatment of Chopart Fracture-Dislocations. AB - The Chopart articular space was used by Francois Chopart (1743-1795) as a practical space for amputation in cases of distal foot tumor. It corresponds to the center of the foot and allows for essential articulation by means of the talo calcaneo-navicular joint (coxa pedis). Chopart fracture-dislocations may therefore include fractures of the navicular, the cuboid, the talus, and calcaneus. The treatment priorities should therefore include addressing all of the injured soft tissues by immediate joint reduction or restoring bony alignment, including the avoidance of threatening compartment syndromes. Subsequent anatomical bone and joint reconstruction, if possible, should first address the talar head and the navicular. The anterior process of the calcaneus and the cuboid should be aligned to preserve foot alignment in the sagittal and horizontal planes. In severe joint destructions, isolated fusion of the calcaneo cuboidal joint may help preserve functional mobility of the foot. Isolated or associated talo-navicular fusion considerably limits functional mobility of the foot. PMID- 26815862 TI - Anatomic Reconstruction of Malunited Chopart Joint Injuries. AB - Fractures and dislocations at the mid-tarsal (Chopart) joint are frequently overlooked or misinterpreted at first presentation. Inadequate joint reduction and stabilization almost invariably lead to painful malunions or nonunions, residual instability, and deformity. Because of the central position and the essential function of the mid-tarsal joint, malunions lead to a considerable impairment of global foot function and the rapid development of posttraumatic arthritis. While secondary anatomical reconstruction with joint preservation would be desirable in order to restore normal foot function, it is amenable only if no symptomatic arthritis or avascular necrosis is present. Over a course of 6 years, eight patients have been treated with secondary correction, joint realignment, and internal fixation. In four of these cases, nonunions of the tarsal navicular were debrided and bone-grafted; in the remaining cases, a corrective osteotomy at the navicular or cuboid was carried out. At 2 years followup, all but one patient were satisfied with the result. One patient underwent fusion of the talonavicular joint for avascular necrosis and collapse of the navicular. The mean American Orthopaedic Foot and Ankle Score (AOFAS) improved significantly from 38.8 preoperatively to 80.8 at follow-up. However, the majority of malunited mid-tarsal fracture-dislocations will require corrective fusion of the affected joint(s) with axial realignment because of manifest posttraumatic arthritis at the time of patient presentation. PMID- 26815863 TI - The Treatment of Lisfranc Injuries: Review of Current Literature. AB - Tarsometatarsal or Lisfranc fracture dislocations (LFD) are rare, easily overlooked, and lead to long-term disability. Recognition of such injuries is important so that adequate treatment can be provided. As many as 20% of LFD are either misdiagnosed or overlooked, and these can be a permanent source of pain in polytraumatic patients after the major fractures have healed. It is important to distinguish pure Lisfranc joint dislocations (LD) from LFD and Chopart-Lisfranc dislocations (CLFD). Here, we discuss the protocols for treating these different types of injury. PMID- 26815864 TI - Reconstruction After Malunited Lisfranc Injuries. AB - Symptomatic secondary osteoarthritis of the Lisfranc joints due to malunion following Lisfranc joint fracture dislocations or ligamentous lesions at the Lisfranc and innominate joint level generally lead to a painful functional loss and a substantial disturbance of the walking performance. Initially missed or inadequately addressed primary lesions still represent the major source of Lisfranc joint malunions. Neuro-osteoarthropathic disorders may also become manifest in the Lisfranc joint region and may be mistaken for truly posttraumatic consequences. Secondary osteoarthritis may be combined with typical multiplanar deformities. The concept of a corrective arthrodesis includes restoration of stable physiologic axes and length proportions of the foot columns. A standardized approach to analyze the clinical picture and corresponding pathomorphology and the transfer into a comprehensive surgical concept which respects the realignment of any component of deformity is a prerequisite for a good functional outcome and a high degree of patient satisfaction. A fusion limited to the medial three rays combined with a soft tissue release may be sufficient for a favorable outcome in the majority of cases and preserve the mobility of the two lateral rays. PMID- 26815865 TI - Trauma Associated with Cardiac Conduction Abnormalities: Population-Based Perspective, Mechanism and Review of Literature. AB - OBJECTIVES: Various cardiac conduction abnormalities have been described as being a result of trauma in many case reports. The aim of this research was to look at the association between trauma (thoracic and cardiac) and conduction abnormalities in a large hospitalized population. METHODS: Cases diagnosed with trauma and various cardiac conduction disorders were identified based on ICD-9-CM discharge diagnoses from 986 acute general hospitals across 33 states in 2001. RESULTS: Independent of potential confounding factors, discharge for blunt cardiac injury (BCI) was associated with a threefold increased risk for cardiac conduction abnormalities (95% confidence interval 2.45-4.51) during hospitalization in 2001. Both BCI and thoracic trauma had a significant association with right bundle branch block (RBBB) in this study (OR 6.04; 95% confidence interval (CI) 3.77-9.67 and OR 1.75; 95% CI 1.38-2.23 respectively). CONCLUSIONS: The results of this study demonstrate the impact of trauma on cardiac conduction abnormalities. This study represents an attempt to consider a mechanism of a complex traumatic cardiac event from a population-based perspective, and may improve the prognosis for patients diagnosed with cardiac or thoracic injuries. PMID- 26815866 TI - Thoracotomy in Thoracic Injuries: Results from a Tertiary Referral Hospital. AB - INTRODUCTION: Critically injured patients may require thoracotomy after a thoracic injury. This study is a retrospective analysis of the results of thoracotomy in patients with thoracic injury. MATERIALS AND METHODS: Injured patients with detectable signs of life on arrival at the hospital and who underwent thoracotomy within 4 h of the injury were investigated. Demographic data and medical records were reviewed for associated injuries, indications, intraoperative findings, and outcomes. The factors affecting the mortality were analyzed. RESULTS: Between April 2003 and January 2009, 488 patients with thoracic injury (blunt/penetrating = 73.7%/26.3%) were treated, and 20 (4.1%) underwent thoracotomy (male/female = 17/3, mean age = 27 +/- 9 years). The injury was penetrating in 15 (11.7%) and blunt in five (1.4%). None of them required an endotracheal intubation at the scene or in transit. The mean transport time was 58 min. Severe and continuous hemothorax (80%), massive air leak, major vessel injury, and trauma causing an open chest wall defect with bleeding were indications of the thoracotomy. Eighty-five percent survived after the surgery (penetrating/ blunt = 86.6%/80%). The mean injury severity score (ISS) of the survivors was lower (21 +/- 9 vs. 39 +/- 10, p = 0.05). Mortality was associated with a lower Glasgow coma scale (GCS) (p = 0.03), a higher ISS (p = 0.05), and a longer transport time (p = 0.05). CONCLUSIONS: Thoracotomy after thoracic injury is a life-saving procedure in selected cases. Lower GCS and higher ISS are associated with increased mortality. Early transport and quick attempts to diagnose the indications necessitating thoracotomy play a significant role in improving the outcome. PMID- 26815867 TI - The Epidemiology of Traumatic Hemothorax in a Level I Trauma Center: Case for Early Video-assisted Thoracoscopic Surgery. AB - OBJECTIVE: Hemothorax is a common sequela of chest trauma. Complications after chest trauma include retained hemothorax and empyema requiring multiple interventions. We studied the epidemiology of hemothorax and its complications at a level I trauma center. METHODS: The trauma registry was reviewed from Jan 1995 toMay 2005.Allpatients >=16 years of agewhowere admitted with hemothorax, an AIS chest score of >= 3, and did not receive an immediate thoracotomy were entered in the study cohort. The patient demographics, details of the injury event, treatments, hospital length of stay (LOS), complications and outcome were analyzed. RESULTS: The study cohort of 522 patients with a hemothorax were treated with 685 chest thoracostomy tubes. Overall, the median ISS was 18 and 62% were penetrating injuries. 109 patients (21%) had a retained hemothorax and required placement of >= 2 chest tubes with a median LOS of 15 days longer than patients with no retained hemothorax (p < 0.0001). The overall complication rate was 5% (26/522). Of these, 20 patients had empyema (3.8%), 8 patients required decortication, and 6 patients received streptokinase treatment. CONCLUSION: More than 1 out of every 5 patients undergoing intervention for trauma-induced hemothorax develops a complication. The development of retained hemothorax is associated with empyema in 15.6% of cases and a 2-week median increase in length of stay. Future research into interventions such as Video-assisted thoracoscopic surgery (VATS) on the day of admission to completely evacuate hemothorax is warranted to reduce complication rates, length of stay and cost. PMID- 26815868 TI - Spinal Epidural Abscess Presenting with Paraplegia Following Delayed Presentation of Traumatic Esophageal Perforation without Spinal Fracture: Lessons to be Learnt. AB - We describe a case of esophageal perforation following blunt chest trauma with delayed presentation as paraplegia secondary to spinal epidural abscess formation. The case highlights the importance of the awareness of the possibility of esophageal injury in patients following road traffic collisions. PMID- 26815869 TI - Small Bowel Volvulus in a Quadriplegic: A Rare Complication of the Simon Nitinol Inferior Vena Cava Filter. AB - The advent and use of inferior vena cava (IVC) filters have reduced the overall incidence of pulmonary embolism in hospitalized patients, but are not without potential complications. With the exponential increase in the utilization of IVC filters over the past two decades, it is important to consider the use of retrievable filters, where indicated, in order to potentially reduce long-term IVC filter-related complications. We report a rare case of small bowel volvulus due to IVC perforation by a Simon Nitinol filter strut in a quadriplegic patient 4 years after IVC filter insertion. PMID- 26815870 TI - Radial Palsy Caused by Ganglion of the Elbow. AB - Ganglion of the humeroradial joint is a relatively rare condition, which may cause local compressive neuropathy. It is usually diagnosed in adults. Sonography of peripheral nerves can be of high value in finding the exact localization of the nerve lesion. We present a case of a healthy 55-year-old woman with radial palsy caused by an elbow ganglion which was resolved following a surgical procedure. PMID- 26815871 TI - Myositis Ossificans Presenting as a Tumor of the Cervical Paraspinal Muscles. AB - Myositis ossificans (MO) is a benign heterotopic bone formation within muscle or soft tissue that is predominantly initiated by trauma. The diagnostic challenge is to distinguish it from bone and soft tissue malignancies. The most common location of MO is the muscles of the thigh and the upper arm, whereas the neck is only rarely involved. A broad range of theories about the etiology of MO exists in the literature, but minor or major trauma can be found in almost every instance. We present a patient in which additional hybrid imaging with singlephoton emission tomography (SPECT) and computed tomography helped to confirm the diagnosis of MO in the paraspinal cervical muscles. PMID- 26815872 TI - Case Report on the Demonstration of Minute Colonic Perforations Caused by Birdshot Injury. AB - Penetrating trauma of the colon is usually diagnosed intraoperatively and missed injuries cause considerable morbidity and mortality. Herein, we described an intraoperative diagnostic method for invisible openings on the colon due to a birdshot injury. A 30-yearold man was admitted to the hospital after sustaining gunshot pellet injuries to his abdomen, back, and extremities. Emergency laparotomy relieved splenic injury and free pellet fragments in the abdomen. A pellet fragment was also palpated in the descending colon. Despite meticulous inspection of the colon, it failed to show the entrance of the pellet. An 18F catheter was passed through the anus and was connected to a CO2 insufflator of the laparoscopy unit. The abdominal cavity was filled with normal saline and 1.5 l of CO2 was inflated into the rectum. Five tiny (2-mm) openings on the retroperitoneal part of the descending colon were demonstrated with the help of the air bubbles. All of the openings were sutureligated and his postoperative course was uneventful. We believe that inflating the colon in cases of abdominal birdshot injuries may allow the demonstration of tiny perforations and provide immediate repairs of missed injuries. PMID- 26815873 TI - Fixation of Subtrochanteric Fractures in Two Patients with Osteopetrosis Using a Distal Femoral Locking Compression Plate of the Contralateral Side. AB - Osteopetrosis or Albers-Schonberg disease is a rare inherited skeletal disorder characterized by increased osteodensity and modeling defects. The fragility of such dense bone may lead to an increased incidence of fractures, especially on the hip and proximal femur. These fractures can pose problems during surgery, as the bones are hard and no medullary cavity is available for intramedullary nailing. Here we report our experience of two sisters who both presented with a subtrochanteric fracture that was fixed using a distal femoral locking compression plate (DF-LCP; Synthes, Obedors, Switzerland) of the contralateral side. PMID- 26815874 TI - Erratum to: Is Nonoperative Treatment still Indicated for Jones Fracture? PMID- 26815876 TI - Polymorphism of 3' UTR of MAMLD1 gene is also associated with increased risk of isolated hypospadias in Indian children: a preliminary report. AB - OBJECTIVE: To study MAMLD1 gene polymorphisms, serum LH and testosterone levels amongst Indian children with isolated hypospadias (IH) and controls. MATERIALS AND METHODS: Screening of the MAMLD1 gene was performed by PCR sequencing method in 100 Indian children aged 0-12 years presenting with IH and 100 controls. LH and testosterone hormone levels were also assessed (categorized in four age-wise groups). RESULTS: IH subjects had significantly higher incidence of MAMLD1 polymorphism as compared to controls (33 vs 15 %, p = 0.01). Of various genomic variants identified in this study, the noteworthy novel ones were missense mutation P299A and single nucleotide polymorphism c.2960C>T in 3' UTR of Exon 7. While p 299A was found to cause protein structural instability consequent to amino acid change, eighty percent subjects with c.2960C>T in 3' UTR of Exon 7 (corresponding to newly discovered currently non-validated exon 11) were found to have lower testosterone levels when compared with their age group mean. IH showed statistically higher incidence of c.2960C>T in comparison to controls (22 vs 10 %, p value 0.046) and about 2.5-folds higher risk of this anomaly. CONCLUSION: Occurrence of MAMDL1 gene polymorphisms, specially of c.2960C>T in 3' UTR of its exon 7 is associated with a higher risk of IH in Indian children, probably by lowering androgenic levels. PMID- 26815878 TI - Neodymium(III) Complexes of Dialkylphosphoric and Dialkylphosphonic Acids Relevant to Liquid-Liquid Extraction Systems. AB - The complexes formed during the extraction of neodymium(III) into hydrophobic solvents containing acidic organophosphorus extractants were probed by single crystal X-ray diffractometry, visible spectrophotometry, and Fourier-transform infrared spectroscopy. The crystal structure of the compound Nd(DMP)3 (1, DMP = dimethyl phosphate) revealed a polymeric arrangement in which each Nd(III) center is surrounded by six DMP oxygen atoms in a pseudo-octahedral environment. Adjacent Nd(III) ions are bridged by (MeO)2POO(-) anions, forming the polymeric network. The diffuse reflectance visible spectrum of 1 is nearly identical to that of the solid that is formed when an n-dodecane solution of di(2 ethylhexyl)phosphoric acid (HA) is saturated with Nd(III), indicating a similar coordination environment around the Nd center in the NdA3 solid. The visible spectrum of the HA solution fully loaded with Nd(III) is very similar to that of the NdA3 material, both displaying hypersensitive bands characteristic of an pseudo-octahedral coordination environment around Nd. These spectral characteristics persisted across a wide range of organic Nd concentrations, suggesting that the pseudo-octahedral coordination environment is maintained from dilute to saturated conditions. PMID- 26815877 TI - Pediatric lymphatic malformations: evolving understanding and therapeutic options. AB - Multimodal treatment of lymphatic malformations continues to expand as new information about the biology and genetics of these lesions is discovered, along with knowledge gained from clinical practice. A patient-centered approach, ideally provided by a multidisciplinary medical and surgical team, should guide timing and modality of treatment. Current treatment options include observation, surgery, sclerotherapy, radiofrequency ablation, and laser therapy. New medical and surgical therapies are emerging, and include sildenafil, propranolol, sirolimus, and vascularized lymph node transfer. The primary focus of management is to support and optimize these patients' quality of life. Researchers continue to study lymphatic malformations with the goal of increasing therapeutic options and developing effective clinical pathways for these complicated lesions. PMID- 26815880 TI - Atrial Natriuretic Peptide in the High Normal Range Is Associated With Lower Prevalence of Insulin Resistance. AB - In 2243 subjects, MR-proANP was measured at baseline. At follow up, MR-proANP levels in the high normal range were associated with lower prevalence of insulin resistance and higher post challenge GIP secretion. PMID- 26815881 TI - Antithyroid Drug Side Effects in the Population and in Pregnancy. AB - OBJECTIVE: Methimazole (MMI) and propylthiouracil (PTU) are both associated with birth defects and may also rarely be associated with agranulocytosis and liver failure. The frequency of these side effects when antithyroid drugs (ATDs) are used in the population in general or in pregnancy remains to be elucidated. DESIGN: All individuals registered as the parent of a live-born child in Denmark, 1973-2008, were identified (n = 2 299 952) and studied from 1995 through 2010 for the use of ATDs. Outcomes were agranulocytosis, liver failure, and birth defects in their offspring. To evaluate the frequency of these side effects associated with the use of ATDs in pregnancy, all live-born pregnancies (n = 830 680), 1996 2008, were identified in a subanalysis. RESULTS: In the population studied, 28 998 individuals redeemed prescriptions of ATDs (exposure in 2115 pregnancies), which was associated with 45 cases of agranulocytosis (one in pregnancy) and 10 cases of liver failure (one in pregnancy). This corresponded to 41 and 11 cases of agranulocytosis and liver failure per 5 million inhabitants during a 10-year period (agranulocytosis: 0.16% of ATDs exposed [MMI: 0.11% vs PTU: 0.27%, P = .02]; liver failure: 0.03% of ATDs exposed [MMI: 0.03% vs PTU: 0.05%, P = .4]). The majority (83%) developed the side effect within 3 months of ATD treatment and 25% during hyperthyroidism relapse. The use of ATDs in pregnancy was associated with birth defects in 3.4% of exposed children (44 cases per 5 million inhabitants per 10 y), and the frequency of birth defects after ATD exposure was 75 times higher than both maternal agranulocytosis and liver failure in pregnancy. CONCLUSIONS: In the Danish population in general, ATDs associated birth defects and agranulocytosis had similar frequencies and were more common than liver failure, whereas for the use of ATDs in pregnancy, birth defects were dominant. The burden of side effects to the use of ATDs can be reduced by restricting the use of ATDs in early pregnancy. PMID- 26815879 TI - Soy Intake Modifies the Relation Between Urinary Bisphenol A Concentrations and Pregnancy Outcomes Among Women Undergoing Assisted Reproduction. AB - CONTEXT: Experimental data in rodents suggest that the adverse reproductive health effects of bisphenol A (BPA) can be modified by intake of soy phytoestrogens. Whether the same is true in humans is not known. OBJECTIVE: The purpose of this study was to evaluate whether soy consumption modifies the relation between urinary BPA levels and infertility treatment outcomes among women undergoing assisted reproduction. SETTING: The study was conducted in a fertility center in a teaching hospital. DESIGN: We evaluated 239 women enrolled between 2007 and 2012 in the Environment and Reproductive Health (EARTH) Study, a prospective cohort study, who underwent 347 in vitro fertilization (IVF) cycles. Participants completed a baseline questionnaire and provided up to 2 urine samples in each treatment cycle before oocyte retrieval. IVF outcomes were abstracted from electronic medical records. We used generalized linear mixed models with interaction terms to evaluate whether the association between urinary BPA concentrations and IVF outcomes was modified by soy intake. MAIN OUTCOME MEASURE: Live birth rates per initiated treatment cycle were measured. RESULTS: Soy food consumption modified the association of urinary BPA concentration with live birth rates (P for interaction = .01). Among women who did not consume soy foods, the adjusted live birth rates per initiated cycle in increasing quartiles of cycle-specific urinary BPA concentrations were 54%, 35%, 31%, and 17% (P for trend = .03). The corresponding live birth rates among women reporting pretreatment consumption of soy foods were 38%, 42%, 47%, and 49% (P for trend = 0.35). A similar pattern was found for implantation (P for interaction = .02) and clinical pregnancy rates (P for interaction = .03) per initiated cycle, where urinary BPA was inversely related to these outcomes among women not consuming soy foods but unrelated to them among soy consumers. CONCLUSION: Soy food intake may protect against the adverse reproductive effects of BPA. As these findings represent the first report suggesting a potential interaction between soy and BPA in humans, they should be further evaluated in other populations. PMID- 26815882 TI - Trace surface-clean palladium nanosheets as a conductivity enhancer in hole transporting layers to improve the overall performances of perovskite solar cells. AB - Surface-clean Pd nanosheets were synthesized and embedded in a hole transport material (HTM) matrix to improve the conductivity of the HTM layer. Applying only a trace amount of Pd nanosheets readily led to a remarkably enhanced performance of perovskite solar cells (PSCs). This finding provides an effective strategy to build efficient charge-transport materials for improving the overall performance of PSCs. PMID- 26815883 TI - Re: "Antimicrobial Susceptibility of Escherichia coli in Uncomplicated Cystitis in the Emergency Department: Is the Hospital Antibiogram an Effective Treatment Guide?". PMID- 26815884 TI - Chronic pain due to Little Leaguer's Shoulder in an adolescent baseball pitcher: a case report. AB - OBJECTIVE: To describe a case of chronic Little Leaguer's Shoulder in reference to pain presentation, physical capabilities, and recovery time. CLINICAL FEATURES: A 17-year-old, junior baseball pitcher presented with shoulder pain when performing high velocity pitching. Conservative treatment for an assumed soft tissue injury failed to resolve the pain, which was regularly aggravated by pitching, and which subsequently prompted further evaluation, and eventual confirmation of Little Leaguer's Shoulder on subsequent computerized tomography (CT) imaging. INTERVENTION AND OUTCOME: Prior to proper diagnosis, conservative treatment had consisted of activity modification, spinal adjusting, laser therapy, shockwave therapy, Active Release Techniques((r)), Kinesiotape,((r)) and rehabilitation. Later, rehabilitation, consisting of general muscle and core strengthening, continued for a further six months under the supervision of college athletic trainers. The athlete was able to return to normal pitching duties approximately 12 months later. SUMMARY: In this case, a potentially damaging bone injury masquerading as a simple musculo-tendinous injury created a diagnostic challenge. The patient eventually recovered with rest, time, strengthening, and eventual compliance to prescribed activity modification. PMID- 26815885 TI - Incidence of Severe Infections and Infection-Related Mortality During the Course of Giant Cell Arteritis: A Multicenter, Prospective, Double-Cohort Study. AB - OBJECTIVE: To assess the incidence of infections leading to hospitalization, the mortality rate related to infections, and the determinants of these factors in patients with giant cell arteritis (GCA). METHODS: In total, 486 patients with GCA (75% women) were enrolled at the time of diagnosis. All patients fulfilled the American College of Rheumatology criteria for GCA. As controls, age- and sex matched subjects were randomly selected from the general population and matched to patients at the time of diagnosis of GCA. Both groups were prospectively followed up over a 5-year period. RESULTS: Severe infections were more frequent among patients with GCA during the first year after diagnosis, compared to general population controls (incidence rate ratio 2.1, 95% confidence interval [95% CI] 1.2-3.4; incidence rate 11.1/100 patient-years [95% CI 8.3-14.6] in patients with GCA versus 5.9/100 patient-years [95% CI 4-8.4] in controls). Specifically, septic shock and infectious colitis were more frequent among the patients with GCA. Mortality caused by infections was higher in patients with GCA compared to controls (P < 0.0001 by log rank test). In analyses adjusted for age, among patients with GCA, a diagnosis of diabetes (hazard ratio [HR] 3.3, 95% CI 1.4-7.7) and a corticosteroid dosage that was >10 mg/day after 12 months of treatment (HR 4.61, 95% CI 1.38-15.36) were associated with death attributed to severe infection. The observed overall incidence of mortality was increased in patients with GCA during the early period of enrollment in the study (before 1997) (P = 0.0001 by log rank test), but thereafter was the same as that in the general population controls. CONCLUSION: Frequencies of severe infections and rates of infection-related mortality are increased during the first year after the diagnosis of GCA. The risk of infection increases in GCA patients with older age or in the presence of diabetes, or is greater when the dosage of corticosteroids has been increased to >10 mg/day after 12 months of treatment. PMID- 26815886 TI - Probing QED and fundamental constants through laser spectroscopy of vibrational transitions in HD(.). AB - The simplest molecules in nature, molecular hydrogen ions in the form of H2(+) and HD(+), provide an important benchmark system for tests of quantum electrodynamics in complex forms of matter. Here, we report on such a test based on a frequency measurement of a vibrational overtone transition in HD(+) by laser spectroscopy. We find that the theoretical and experimental frequencies are equal to within 0.6(1.1) parts per billion, which represents the most stringent test of molecular theory so far. Our measurement not only confirms the validity of high order quantum electrodynamics in molecules, but also enables the long predicted determination of the proton-to-electron mass ratio from a molecular system, as well as improved constraints on hypothetical fifth forces and compactified higher dimensions at the molecular scale. With the perspective of comparisons between theory and experiment at the 0.01 part-per-billion level, our work demonstrates the potential of molecular hydrogen ions as a probe of fundamental physical constants and laws. PMID- 26815888 TI - Enhanced visible light photocatalytic performance of ZnO nanowires integrated with CdS and Ag2S. AB - A series of ZnO-CdS-Ag2S ternary nanostructures with different amounts of Ag2S were prepared using simple and low-cost successive ionic layer adsorption and reaction (SILAR) and a chemical precipitation method. The ZnO nanowires, with a diameter of ~ 100 nm and a length of ~ 1 MUm, were modified by coating CdS and Ag2S. CdS has a high absorption coefficient and can efficiently match with the energy levels of ZnO, which can enhance the light absorption ability of the nanostructures. In addition, Ag2S with a narrow band gap was used as the main light absorber and played an important role in increasing the light absorption in the visible light region. The photocatalytic activity of the ZnO-CdS-Ag2S ternary nanostructures was investigated using the degradation of methyl orange (MO) in an aqueous solution under visible light. The ZnO-CdS-Ag2S ternary nanostructures were found to be more efficient than ZnO nanowires, ZnO-CdS nanowires, and ZnO Ag2S nanowires. There is 7.68 times more photocatalytic activity for MO degradation in terms of the rate constant for ZnO-CdS-Ag2S 15-cycle ternary nanostructure compared to the as-grown ZnO. Furthermore, the effect of the amount of Ag2S and CdS on the ZnO surface on the photocatalytic activity was analyzed. The superior photo-absorption properties and photocatalytic performance of the ZnO-CdS-Ag2S ternary nanostructures can be ascribed to the heterostructure, which enhanced the separation of the photo-induced electron-hole pairs. In addition, visible light could be absorbed by ZnO-CdS-Ag2S ternary nanostructures rather than by ZnO. PMID- 26815887 TI - Five-Year Mortality and Hospital Costs Associated with Surviving Intensive Care. AB - RATIONALE: Survivors of critical illness experience significant morbidity, but the impact of surviving the intensive care unit (ICU) has not been quantified comprehensively at a population level. OBJECTIVES: To identify factors associated with increased hospital resource use and to ascertain whether ICU admission was associated with increased mortality and resource use. METHODS: Matched cohort study and pre/post-analysis using national linked data registries with complete population coverage. The population consisted of patients admitted to all adult general ICUs during 2005 and surviving to hospital discharge, identified from the Scottish Intensive Care Society Audit Group registry, matched (1:1) with similar hospital control subjects. Five-year outcomes included mortality and hospital resource use. Confounder adjustment was based on multivariable regression and pre/post within-individual analyses. MEASUREMENTS AND MAIN RESULTS: Of 7,656 ICU patients, 5,259 survived to hospital discharge (5,215 [99.2%] matched to hospital control subjects). Factors present before ICU admission (comorbidities/pre-ICU hospitalizations) were stronger predictors of hospital resource use than acute illness factors. In the 5 years after the initial hospital discharge, compared with hospital control subjects, the ICU cohort had higher mortality (32.3% vs. 22.7%; hazard ratio, 1.33; 95% confidence interval, 1.22-1.46; P < 0.001), used more hospital resources (mean hospital admission rate, 4.8 vs. 3.3/person/5 yr), and had 51% higher mean 5-year hospital costs ($25,608 vs. $16,913/patient). Increased resource use persisted after confounder adjustment (P < 0.001) and using pre/post-analyses (P < 0.001). Excess resource use and mortality were greatest for younger patients without significant comorbidity. CONCLUSIONS: This complete, national study demonstrates that ICU survivorship is associated with higher 5-year mortality and hospital resource use than hospital control subjects, representing a substantial burden on individuals, caregivers, and society. PMID- 26815889 TI - Innovation in trauma care: 2nd World Trauma Congress and 15th European Congress of Trauma and Emergency Surgery. PMID- 26815890 TI - Update on the definition of polytrauma. AB - PURPOSE: The definition and use of the term "polytrauma" is inconsistent and lacks validation. This article describes the historical evolution of the term and geographical differences in its meaning, examines the challenges faced in defining it adequately in the current context, and summarizes where the international consensus process is heading, in order to provide the trauma community with a validated and universally agreed upon definition of polytrauma. CONCLUSION: A lack of consensus in the definition of "polytrauma" was apparent. According to the international consensus opinion, both anatomical and physiological parameters should be included in the definition of polytrauma. An Abbreviated Injury Scale (AIS) based anatomical definition is the most practical and feasible given the ubiquitous use of the system. Convincing preliminary data show that two body regions with AIS >2 is a good marker of polytrauma-better than other ISS cutoffs, which could also indicate monotrauma. The selection of the most accurate physiological parameters is still underway, but they will most likely be descriptors of tissue hypoxia and coagulopathy. PMID- 26815891 TI - The coagulopathy of trauma. AB - Trauma is a leading cause of death, with uncontrolled hemorrhage and exsanguination being the primary causes of preventable deaths during the first 24 h following trauma. Death usually occurs quickly, typically within the first 6 h after injury. One out of four patients arriving at the Emergency Department after trauma is already in hemodynamic and hemostatic depletion. This early manifestation of hemostatic depletion is referred to as the coagulopathy of trauma, which may distinguished as: (i) acute traumatic coagulopathy (ATC) and (ii) iatrogenic coagulopathy (IC). The principle drivers of ATC have been characterized by tissue trauma, inflammation, hypoperfusion/shock, and the acute activation of the neurohumoral system. Hypoperfusion leads to an activation of protein C with cleavage of activated factors V and VIII and the inhibition of plasminogen activator inhibitor-1 (PAI-1), with subsequent fibrinolysis. Endothelial damage and activation results in Weibel-Palade body degradation and glycocalyx shedding associated with autoheparinization. In contrast, there is an IC which occurs secondary to uncritical volume therapy, leading to acidosis, hypothermia, and hemodilution. This coagulopathy may, then, be an integral part of the "vicious cycle" when combined with acidosis and hypothermia. The awareness of the specific pathophysiology and of the principle drivers underlying the coagulopathy of trauma by the treating physician is paramount. It has been shown that early recognition prompted by appropriate and aggressive management can correct coagulopathy, control bleeding, reduce blood product use, and improve outcome in severely injured patients. This paper summarizes: (i) the current concepts of the pathogenesis of the coagulopathy of trauma, including ATC and IC, (ii) the current strategies available for the early identification of patients at risk for coagulopathy and ongoing life-threatening hemorrhage after trauma, and (iii) the current and updated European guidelines for the management of bleeding and coagulopathy following major trauma. PMID- 26815892 TI - The effect of evolving trauma care on the development of multiple organ dysfunction syndrome. AB - INTRODUCTION: Multiple organ dysfunction syndrome (MODS) is still a major threat to polytrauma patients, since sepsis-related organ failure is the most common cause of late mortality in these patients. In this article, the development of trauma surgery and evolution of trauma care from early total care to damage control surgery is discussed. Increasing knowledge of the pathophysiology of trauma has enabled us to identify the inflammatory response induced by trauma. By understanding the pathophysiology, we may be able to fully comprehend the origin of multiple organ dysfunction related sepsis. Further, it is important to appreciate the influence of surgery on the inflammatory response induced by trauma, and subsequently on the development of inflammatory complications. It is crucial to offer the polytrauma patient the appropriate type of surgery at the right time to prevent further deterioration. CONCLUSION: MODS is still highly lethal, and once it has developed it is difficult to treat, so it is vital to be able to predict its occurrence. If we knew how to predict MODS, we might be able to develop strategies to prevent this syndrome. PMID- 26815893 TI - Planned re-laparotomy and the need for optimization of physiology and immunology. AB - Planned re-laparotomy or damage control laparotomy (DCL), first described by Dr. Harlan Stone in 1983, has become a widely utilized technique in a broad range of patients and operative situations. Studies have validated the use of DCL by demonstrating decreased mortality and morbidity in trauma, general surgery and abdominal vascular catastrophes. Indications for planned re-laparotomy include severe physiologic derangements, coagulopathy, concern for bowel ischemia, and abdominal compartment syndrome. The immunology of DCL patients is not well described in humans, but promising animal studies suggest a benefit from the open abdomen (OA) and several human trials on this subject are currently underway. Optimal critical care of patients with OA's, including sedation, paralysis, nutrition, antimicrobial and fluid management strategies have been associated with improved closure rates and recovery. PMID- 26815894 TI - Damage control strategies in the management of acute injury. AB - Traumatic injury is the leading cause of death worldwide. The rapid evaluation and correction of injuries in these patients is paramount to preventing uncontrolled decompensation and death. Damage control strategies are a compendium of techniques refined over decades of surgical care that focus on the rapid correction of deranged physiology, control of contamination and blood loss, and resuscitation of critical patients. Damage control resuscitation (DCR) focuses on the replacement of lost blood volume in a manner mimicking whole blood, control of crystalloid administration, and permissive hypotension. Damage control laparotomy controls gastrointestinal contamination and bleeding in the operative suite, allowing rapid egress to the intensive care unit for ongoing resuscitation. Pelvic packing, an adjunct to DCR, provides a means to control hemorrhage from severe pelvic fractures. Temporary vascular shunts restore perfusion, while resuscitation and reconstruction are ongoing. Taken together, these strategies provide the trauma surgeon with a powerful arsenal to preserve life in the transition from injury to the shock trauma room to the intensive care unit. PMID- 26815895 TI - Best practice for needlestick injuries. AB - PURPOSE: Needlestick injuries (NSIs) are a significant health hazard. Occupational transmission of bloodborne pathogens among healthcare workers (HCWs) is rare but has been repeatedly reported in the literature. METHODS: In October 2010, new regulations were introduced for medical aftercare of HCWs following NSIs at the University Hospital Frankfurt. In June 2013, a university hospital wide early intervention program was introduced that gives HCWs immediate 24/7/365 access to an HIV postexposure prophylaxis kit after confirmed or probable occupational HIV exposure. RESULTS: Interdisciplinary collaboration between the attending surgeon and occupational health as well as infectious disease specialists facilitates optimal postexposure medical treatment of HCWs who suffer NSIs. Complete reporting of NSIs is a prerequisite for achieving optimal treatment of the affected HCWs. CONCLUSION: An NSI is an emergency and needs to be evaluated immediately and, if necessary, treated as soon as possible. A standardized algorithm for initial diagnostic and treatment has proven to be helpful. PMID- 26815896 TI - Ultrasound diagnosis of supracondylar fractures in children. AB - PURPOSE: The objective of our study was to evaluate the safety and accuracy of ultrasound (US) compared to standard radiographs in diagnosing supracondylar fractures (SCFs) of the humerus in children. PATIENTS AND METHODS: A total of 106 children (aged between 1 and 13 years) with clinically suspected SCF of the humerus were primarily examined by US followed by standard two-plane radiographs of the elbow. US was conducted with a linear scanner viewing the distal humerus from seven standardized sectional planes. US fracture diagnosis was established either by a cortical bulging or cortical gap, or by a positive dorsal fat pad (dFP) sign. X-ray diagnosis was stated by an independent pediatric radiologist and, afterwards, compared to our US findings. Sonographic and radiographic findings were collected in a contingency table. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for US fracture diagnosis were calculated according to the radiographs. In addition, by identifying significant angulation and/or disrupture, SCFs were classified as non operative/stable and operative/instable SCFs according to the AO Pediatric Fracture Classification System. RESULTS: By US, a SCF could be excluded in 43 patients and in 63 patients, a fracture was diagnosed. In contrast, by radiographs, an SCF could be excluded in 46 patients and in 60 patients, a fracture was diagnosed. For US fracture diagnosis in comparison to radiographs, we calculated a sensitivity of 100 %, a specificity of 93.5 %, an NPV of 100 %, and a PPV of 95.2 %. Thirty-nine SCFs were sonographically classified as stable grades 1/2 SCFs and confirmed in 37 patients by X-rays. All four operative/instable SCFs were correctly identified by US. CONCLUSION: By identifying a positive dFP sign and/or cortical lesions of the distal humerus, SCFs can be detected very sensitively by US. Even the estimation of fracture displacement seems to be possible. We suggest US as an applicable alternative method in the primary evaluation of suspected SCF in children, guiding further diagnostics, where appropriate. After minor injuries, if clinical assessment for an elbow fracture is low and US examination is negative for fracture, additional radiographs are dispensable. Thereby, the amount of X-ray burden during childhood can be reduced, without loss of diagnostic safety. PMID- 26815897 TI - Polytrauma at the Emergency Department; can we relate arterial blood gas analysis to a shock classification? AB - OBJECTIVE: Shock is defined as a change of circulation which results in hypoxia at the tissue level. Lactate and base deficit (BD) are associated with a high risk of multiple organ dysfunction in trauma patients. In this study we evaluated the influence of early recognition of shock in trauma patients. METHODS: In a retrospective study, relevant data were collected from the Radboud University Nijmegen Medical Centre (RUNMC) database between January 2009 and December 2010. Vital parameters were taken at the accident scene, and patients were divided into four shock classes. Arterial blood gas analysis was performed on arrival in the emergency department. Statistical analysis was performed with SPSS version 17.0. Statistical significance was assumed at p <= 0.05. RESULTS: A total of 255 patients were included. Patients who suffered from prehospital shock, and those who were intubated prior to hospital admittance showed a bad outcome, presenting with a more severe metabolic acidosis, higher ISS and higher mortality. There was a significant difference for bicarbonate and BD between shockclass I + II and shockclass III + IV, respectively 22.7 vs. 19.7 and -3.4 vs. -6.9. Intubated patients had a decreased bicarbonate and BD compared to not intubated patients, respectively 21.81 vs. 23.24 and -5.08 vs. -2.38. Mortality and ISS were higher in patients in shock class III and IV. Significant differences in serum lactate levels were not found. CONCLUSIONS: Prehospital shock influences patient outcome; outcome of patients is related to initial shock classification. Further validation of our shock classification, however, is necessary. PMID- 26815898 TI - Beta-hemolytic streptococcal infections in trauma patients. AB - PURPOSE: beta-hemolytic streptococci (betaHS) causes a diverse array of human infections. The molecular epidemiology of beta-hemolytic streptococcal infections in trauma patients has not been studied. This study reports the molecular and clinical epidemiology of beta-hemolytic streptococcal infections at a level 1 trauma centre of India. METHODS: A total of 117 isolates of betaHS were recovered from clinical samples of trauma patients. The isolates were identified to species level and subjected to antimicrobial susceptibility testing. Polymerase chain reaction (PCR) assay was done to detect exotoxin virulence genes. The M protein gene (emm gene) types of GAS strains were ascertained by sequencing. RESULTS: Group A Streptococcus (GAS) was the most common isolate (64 %), followed by group G Streptococcus (23 %). A large proportion of GAS produced speB (99 %), smeZ (91 %), speF (95 %) and speG (87 %). smeZ was produced by 22 % of GGS. A total of 25 different emm types/subtypes were seen in GAS, with emm 11 being the most common. Resistance to tetracycline (69 %) and erythromycin (33 %) was commonly seen in GAS. CONCLUSIONS: beta-hemolytic streptococcal infections in Indian trauma patients are caused by GAS and non-GAS strains alike. A high diversity of emm types was seen in GAS isolates, with high macrolide and tetracycline resistance. SpeA was less commonly seen in Indian GAS isolates. There was no association between disease severity and exotoxin gene production. PMID- 26815899 TI - Dalteparin versus Enoxaparin for the prevention of venous thromboembolic events in trauma patients. AB - BACKGROUND: The use of low-molecular-weight heparin (LMWH) for the chemoprophylaxis of venous thromboembolism (VTE) in trauma patients is supported by Level-1 evidence. Because Enoxaparin was the agent used in the majority of studies for establishing the efficacy of LMWH in VTE, it remains unclear if Dalteparin provides an equivalent effect. OBJECTIVE: To compare Dalteparin to Enoxaparin and investigate their equivalence as VTE prophylaxis in trauma. PATIENTS/SETTING: Trauma patients receiving VTE chemoprophylaxis in the Surgical Intensive Care Unit of a Level-1 Trauma Center from 2009 (Enoxaparin) to 2010 (Dalteparin) were included. MEASUREMENTS: The primary outcome was the incidence of clinically significant VTE. Secondary outcomes included heparin-induced thrombocytopenia (HIT), major bleeding, and drug acquisition cost savings. Equivalence margins were set between -5 and 5 %. MAIN RESULTS: A total of 610 patient records (277 Enoxaparin, 333 Dalteparin) were reviewed. The two study groups did not differ significantly: blunt trauma 67 vs. 62 %, p = 0.27; mean Injury Severity Score (ISS) 17 +/- 10 vs. 16 +/- 10, p = 0.34; Acute Physiology and Chronic Health Evaluation (APACHE) II score 17 +/- 9 vs. 17 +/- 10, p = 0.76; time to first dose of LMWH 69 +/- 98 vs. 65 +/- 67 h, p = 0.57). The rates of deep venous thrombosis (DVT) (3.2 vs. 3.3 %, p = 1.00), pulmonary emboli (PE) (1.8 vs. 1.2 %, p = 0.74), and overall VTE (5.1 vs. 4.5 %, p = 0.85) did not differ. The absolute difference in the incidence of overall VTE was 0.5 % [95 % confidence interval (CI): -2.9, 4.0 %, p = 0.85]. The 95 % CI was within the predefined equivalence margins. There were no significant differences in the frequency of HIT or major bleeding. The total year-on-year cost savings, achieved with 277 patients during the switch to Dalteparin, was estimated to be $107,778. CONCLUSIONS: Dalteparin is equivalent to Enoxaparin in terms of VTE in trauma patients and can be safely used in this population, with no increase in complications and significant cost savings. PMID- 26815900 TI - Distal femoral replacement for selective periprosthetic fractures above a total knee arthroplasty. AB - BACKGROUND AND AIM: The management of distal femur periprosthetic fractures in the elderly remains a challenge. The aim of this study was to evaluate the results of distal segmental femur replacement as an alternative to fixation in complex distal femoral periprosthetic fractures in elderly patients. METHODS: Twelve patients were included in this prospective study, with a mean age of 78 years (range 68-90 years); incidentally, all were female. Fractures of the distal femur were classified as per Kim et al.'s classification (Clin Orthop Relat Res 446:167-175, 2006); our series included eight patients with type III and four patients with type II periprosthetic fractures. All 12 patients were treated with segmental distal femur replacement (Zimmer Inc., Warsaw, IN, USA). Nine patients required 90 cm and three patients required 130 cm of distal femur segment with a rotating hinge knee prosthesis. RESULTS: The mean follow up period was 20 months (range 15-28 months), with no major surgical complications reported. The mean duration of hospital stay following surgery was 12 days (range 7-36 days). All patients were mobilising full weight-bearing by day 3. All patients returned to their prior living arrangements. Ten patients returned to their original domicile, with one patient being discharged to a care home requiring minimal ambulatory assistance. The remaining two patients returned to their care homes. CONCLUSIONS: WOMAC scores improved from the pre-injury state with a mean of 49.62 to 72.54 post-surgery (p-value of 0.0001). The Knee Society scores, possible only following surgery, had a mean value of 72. The mean VAS pain score was 1.75 (0 = no pain to 10 = worst pain ever felt). The average range of knee flexion was from 4 degrees to 89 degrees (range -5 degrees to 110 degrees ). The mean SF-36 physical functioning score was 45.64 [range 40.70-48.90; standard deviation (SD) 2.62] and the mean SF-36 mental functioning score was 52.94 (range 45.8-57.70; SD -3.38). PMID- 26815902 TI - Estes News. PMID- 26815901 TI - Mortality after proximal femur fracture with a delay of surgery of more than 48 h. AB - PURPOSE: For hip fractures, guidelines require surgery as soon as possible, but not later than 48 h. Some authors observed a positive and some a negative effect of early operation on mortality rate. The aim was to evaluate the mortality rate of patients with a delay of surgery >48 h after admission, as well as influencing factors and reasons for delay. METHODS: One hundred and thirty-six patients with hip fractures (>65a) from 2007 to 2011 were included. Comorbidities, the American Society of Anaesthesiologists (ASA) classification, time of admission and surgery, and mortality were recorded up to 12 months. Reasons for delay were divided into administrative-related or patient-related. The following time intervals were observed: 48.01-72 h (2-3 days), 72.01-120 h (3-5 days), 120.01 168 h (5-7 days), 168 h (>7 days). RESULTS: 94.9 % of the reasons for delay were patient-related. The mean survival times of the first three intervals were almost the same (9.5-9.9 months) (p = 0.75). The last group had a significantly shorter survival time (7.8 months). Summarizing the first three groups, a significant shorter (p = 0.03) survival time and significantly higher (p = 0.04) 12-month mortality rate in patients with a delay >7 days was observed. The probability of death was primarily dependent on the ASA classification (p < 0.0001) and secondarily on the patient's age at the time of injury (p = 0.005). CONCLUSIONS: In hip fractures, reasons for a delay >48 h are mainly patient-related. A delay up to 7 days did not influence survival time and mortality negatively. The higher the value of the ASA classification and the older the patient was at the time of injury, the higher the mortality rate and the shorter the survival time. PMID- 26815903 TI - Analysis of GPR101 and AIP genes mutations in acromegaly: a multicentric study. AB - This multicentric study aimed to investigate the prevalence of the G protein coupled receptor 101 (GPR101) p.E308D variant and aryl hydrocarbon receptor interacting protein (AIP) gene mutations in a representative cohort of Italian patients with acromegaly. 215 patients with GH-secreting pituitary adenomas, referred to 4 Italian referral centres for pituitary diseases, have been included. Three cases of gigantism were present. Five cases were classified as FIPA. All the patients have been screened for germline AIP gene mutations and GPR101 gene p.E308D variant. Heterozygous AIP gene variants have been found in 7 patients (3.2 %). Five patients carried an AIP mutation (2.3 %; 4 females): 3 patients harboured the p.R3O4Q mutation, one had the p.R304* mutation and the last one the IVS3+1G>A mutation. The prevalence of AIP mutations was 3.3 % and 2.8 % when considering only the patients diagnosed when they were <30 or <40-year old, respectively. Furthermore, 2.0 % of the patients with a pituitary macroadenoma and 4.2 % of patients resistant to somatostatin analogues treatment were found to harbour an AIP gene mutation. None of the patients was found to carry the GPR101 p.E308D variant. The prevalence of AIP gene mutations among our sporadic and familial acromegaly cases was similar to that one reported in previous studies, but lower when considering only the cases diagnosed before 40 years of age. The GPR101 p.E308D change is unlikely to have a role in somatotroph adenomas tumorigenesis, since none of our sporadic or familial patients tested positive for this variant. PMID- 26815904 TI - Assessment of trabecular bone score (TBS) in overweight/obese men: effect of metabolic and anthropometric factors. AB - The "trabecular bone score" (TBS) indirectly explores bone quality, independently of bone mineral density (BMD). We investigated the effects of anthropometric and metabolic parameters on TBS in 87 overweight/obese men. We assessed BMD and TBS by DXA, and some parameters of glucose metabolism, sex-and calciotropic hormone levels. Regression models were adjusted for either age and BMI, or age and waist circumference, or age and waist/hip ratio, also considering BMI >35 (y/n) and metabolic syndrome (MS) (y/n). Correlations between TBS and parameters studied were higher when correcting for waist circumference, although not significant in subjects with BMI >35. The analysis of covariance showed that the same model always had a higher adjusted r-square index. BMD at lumbar spine and total hip, fasting glucose, bioavailable testosterone, and sex hormone-binding globulin are the only covariates having a significant effect (p < 0.05) on the variations of TBS. The presence of MS negatively affected only the association between TBS and BMD at total hip. We did not find any significant effect of BMI >35 on TBS values or significant interaction terms between each covariate and either BMI >35 or the presence of MS. Obesity negatively affected TBS, despite unchanged BMD. Alterations of glucose homeostasis and sex hormone levels seem to influence this relationship, while calciotropic hormones have no role. The effect of waist circumference on TBS is more pronounced than that of BMI. PMID- 26815905 TI - Anatomy of the bacitracin resistance network in Bacillus subtilis. AB - Protection against antimicrobial peptides (AMPs) often involves the parallel production of multiple, well-characterized resistance determinants. So far, little is known about how these resistance modules interact and how they jointly protect the cell. Here, we studied the interdependence between different layers of the envelope stress response of Bacillus subtilis when challenged with the lipid II cycle-inhibiting AMP bacitracin. The underlying regulatory network orchestrates the production of the ABC transporter BceAB, the UPP phosphatase BcrC and the phage-shock proteins LiaIH. Our systems-level analysis reveals a clear hierarchy, allowing us to discriminate between primary (BceAB) and secondary (BcrC and LiaIH) layers of bacitracin resistance. Deleting the primary layer provokes an enhanced induction of the secondary layer to partially compensate for this loss. This study reveals a direct role of LiaIH in bacitracin resistance, provides novel insights into the feedback regulation of the Lia system, and demonstrates a pivotal role of BcrC in maintaining cell wall homeostasis. The compensatory regulation within the bacitracin network can also explain how gene expression noise propagates between resistance layers. We suggest that this active redundancy in the bacitracin resistance network of B. subtilis is a general principle to be found in many bacterial antibiotic resistance networks. PMID- 26815906 TI - Absence of human herpesvirus 6B detection in association with illness in children undergoing cancer chemotherapy. AB - The lymphotropic herpesviruses, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus 6B (HHV-6B) can reactivate and cause disease in organ transplant recipients; the contributions of HHV-6A and HHV-7 to disease are less certain. Less is known about their pathogenic roles in children undergoing treatment for malignancies. Children with newly diagnosed cancer were followed for 24 months. Clinical information and blood samples were collected during routine visits and during acute visits for fever or possible viral infections. Lymphotropic herpesvirus DNA in blood was measured by polymerase chain reaction (PCR). Although HHV-6B DNA was detected at least once in about half of the patients; the other viruses were seldom detected. There was no association between HHV-6B detection and individual acute clinical events, however, HHV-6B detection was more common in children who experienced more frequent acute clinical events. In children being treated for various malignancies, HHV-6B detection was common, but was not associated with individual events of acute illness. Thus, if HHV-6B is not assessed longitudinally, clinical events may be misattributed to the virus. The elevated frequency of detection of HHV-6B in sicker children is consistent with prior reports of its detection during apparently unrelated acute clinical events. J. Med. Virol. 88:1427-1437, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26815907 TI - The effect of climate manipulations on the herbivory of the pest slug Deroceras reticulatum (Muller, 1774) (Pulmonata: Agriolimacidae). AB - The pestiferous status of the terrestrial slug Deroceras reticulatum and the strong dependence of its biology and ecology on climatic factors have driven research on the potential responses of the slug to predicted scenarios of climate change. Here, we report two short-term experiments performed outdoors, under seminatural conditions, to assess the behavioural response of D. reticulatum to different climate manipulations in terms of herbivory, by measuring over 7 days the damage inflicted by slug populations to lettuce seedlings. The climate manipulations tested emulate predicted climatic conditions for northwest Spain, specifically winter warming and increased summer rainfall, in contrast respectively with normal winter conditions and summer without rain conditions. In a winter experiment, we compared a normal winter treatment with a winter warming treatment; with respect to the normal winter treatment, the winter warming treatment was characterised by higher temperature, lower relative humidity and the absence of rainfall. In a summer experiment, we compared a summer drought treatment with an increased summer rainfall treatment; with respect to the summer drought treatment, the increased summer rainfall treatment was characterised by the presence of rainfall, while the conditions of temperature and relative humidity were similar in both treatments. Neither winter warming nor increased summer rainfall did lead to a significant increase on the number of seedlings damaged by the slugs. However, with both treatments, we found a moderate increase on the amount of damage suffered by the seedlings. The results are discussed in the context of the potential responses of D. reticulatum to future climatic conditions. PMID- 26815908 TI - Treatment of nausea and vomiting during pregnancy -a cross-sectional study among 712 Norwegian women. AB - PURPOSE: The purposes of this study were to investigate the treatments used for nausea and vomiting of pregnancy (NVP) according to NVP severity among Norwegian women and to assess whether maternal characteristics and attitudes were related to the use of pharmacological treatment of NVP. METHODS: This is a cross sectional Web-based study. Pregnant women and mothers with children <=1 year of age were eligible to participate. Data were collected through an anonymous online questionnaire accessible from November 10th, 2014 to January 31st, 2015. RESULTS: In total, 712 women were included in the study, of which 62 (8.7 %), 439 (61.7 %) and 210 (29.5 %) had mild, moderate and severe NVP, respectively, according to the Pregnancy-Unique Quantification of Emesis (PUQE) classification. A total of 277 (38.9 %) women had used one or more antiemetics, of which meclizine, closely followed by metoclopramide, was the most commonly used. Different drug utilisation patterns were found between the groups of women with mild, moderate and severe NVP. Many with moderate or severe symptoms did not use any pharmacological treatment (70.2 and 32.9 %, respectively). Sick leave was given without initiating medical treatment in 266 (62.1 %) women. The women's beliefs about medicines had an important impact on their use of medicines for NVP. CONCLUSIONS: A large proportion of women suffered from moderate to severe symptoms of NVP, many of whom did not receive any pharmacological treatment. Many women, who had been on sick leave due to NVP, were not prescribed medicines. PMID- 26815910 TI - Expression of terminal oxidases under nutrient-starved conditions in Shewanella oneidensis: detection of the A-type cytochrome c oxidase. AB - Shewanella species are facultative anaerobic bacteria that colonize redox stratified habitats where O2 and nutrient concentrations fluctuate. The model species Shewanella oneidensis MR-1 possesses genes coding for three terminal oxidases that can perform O2 respiration: a bd-type quinol oxidase and cytochrome c oxidases of the cbb3-type and the A-type. Whereas the bd- and cbb3-type oxidases are routinely detected, evidence for the expression of the A-type enzyme has so far been lacking. Here, we investigated the effect of nutrient starvation on the expression of these terminal oxidases under different O2 tensions. Our results reveal that the bd-type oxidase plays a significant role under nutrient starvation in aerobic conditions. The expression of the cbb3-type oxidase is also modulated by the nutrient composition of the medium and increases especially under iron-deficiency in exponentially growing cells. Most importantly, under conditions of carbon depletion, high O2 and stationary-growth, we report for the first time the expression of the A-type oxidase in S. oneidensis, indicating that this terminal oxidase is not functionally lost. The physiological role of the A type oxidase in energy conservation and in the adaptation of S. oneidensis to redox-stratified environments is discussed. PMID- 26815911 TI - Expression and functional roles of estrogen receptor GPR30 in human intervertebral disc. AB - Estrogen withdrawal, a characteristic of female aging, is associated with age related intervertebral disc (IVD) degeneration. The function of estrogen is mediated by two classic nuclear receptors, estrogen receptor (ER)-alpha and beta, and a membrane bound G-protein-coupled receptor 30 (GPR30). To date, the expression and function of GPR30 in human spine is poorly understood. This study aimed to evaluate GPR30 expression in IVD, and its role in estrogen-related regulation of proliferation and apoptosis of disc nucleus pulposus (NP) cells. GPR30 expression was examined in 30 human adult NP and 9 fetal IVD. Results showed that GPR30 was expressed in NP cells at both mRNA and protein levels. In human fetal IVD, GPR30 protein was expressed in the NP at 12-14 weeks gestation, but was undetectable at 8-11 weeks. The effect of 17beta-estradiol (E2) on GPR30 mediated proliferation and interleukin-1beta (IL-1beta)-induced apoptosis of NP cells was investigated. Cultured NP cells were treated with or without E2, GPR30 antagonist G36, and ER antagonist ICI 182,780. NP cell viability was tested by MTS assay. Apoptosis was determined by flow cytometry using fluorescence labeled annexin-V, TUNEL assay and immumnocytochemical staining of activated caspase-3. E2 enhanced cell proliferation and prevented IL-1beta-induced cell death, but the effect was partially blocked by G36 and completely abrogated by a combination of ICI 182,780 and G36. This study demonstrates that GPR30 is expressed in human IVD to transmit signals triggering E2-induced NP cell proliferation and protecting against IL-1beta-induced apoptosis. The effects of E2 on NP cells require both GPR30 and classic estrogen receptors. PMID- 26815912 TI - Increase in prostate stem cell antigen expression in prostatic hyperplasia induced by testosterone and 17beta-estradiol in C57BL mice. AB - Estradiol (E2) is known to act synergistically with testosterone (T) for the development of prostatic hyperplasia in rats and dogs, but murine prostate is less responsive to hormonal stimulation. However, a recent study revealed that the combined administration of E2 and T induced prostatic hyperplasia with bladder outlet obstruction in C57BL mice. To understand the mechanisms underlying the hormonal induction of prostatic hyperplasia, the expression of growth factors and their receptors, androgen receptor, estrogen receptor (ER), and prostatic secretory proteins was investigated. Ten-week-old male C57BL mice were treated with T (30mg) or T+E2 (0.5mg) for 10 weeks, and prostatic lobes were dissected and subjected to quantitative RT-PCR and immunoblotting analysis. T administration appeared to induce glandular prostatic growth, while with T+E2 administration this growth was greater and accompanied by extreme bladder enlargement. The expression of prostate stem cell antigen (PSCA) mRNA and protein was increased in prostate tissue in the T group. The combined administration of E2 with T prominently enhanced PSCA expression, along with increased insulin growth factor 1 mRNA levels and decreased estrogen receptor beta mRNA expression. The synergistic effect of E2 on the expression of PSCA suggests that this protein may play an important role in the hormone-induced development of prostatic hyperplasia. PMID- 26815913 TI - Mechanism of Aloe Vera extract protection against UVA: shelter of lysosomal membrane avoids photodamage. AB - The premature aging (photoaging) of skin characterized by wrinkles, a leathery texture and mottled pigmentation is a well-documented consequence of exposure to sunlight. UVA is an important risk factor for human cancer also associated with induction of inflammation, immunosuppression, photoaging and melanogenesis. Although herbal compounds are commonly used as photoprotectants against the harmful effects of UVA, the mechanisms involved in the photodamage are not precisely known. In this study, we investigated the effects of Aloe Vera (Aloe barbadensis mil) on the protection against UVA-modulated cell killing of HaCaT keratinocytes. Aloe Vera exhibited the remarkable ability of reducing both in vitro and in vivo photodamage, even though it does not have anti-radical properties. Interestingly, the protection conferred by Aloe Vera was associated with the maintenance of membrane integrity in both mimetic membranes and intracellular organelles. The increased lysosomal stability led to a decrease in lipofuscinogenesis and cell death. This study explains why Aloe Vera extracts offer protection against photodamage at a cellular level in both the UV and visible spectra, leading to its beneficial use as a supplement in protective dermatological formulations. PMID- 26815914 TI - Hierarchical thermoelectrics: crystal grain boundaries as scalable phonon scatterers. AB - Thermoelectric materials are strategically valuable for sustainable development, as they allow for the generation of electrical energy from wasted heat. In recent years several strategies have demonstrated some efficiency in improving thermoelectric properties. Dopants affect carrier concentration, while thermal conductivity can be influenced by alloying and nanostructuring. Features at the nanoscale positively contribute to scattering phonons, however those with long mean free paths remain difficult to alter. Here we use the concept of hierarchical nano-grains to demonstrate thermal conductivity reduction in rocksalt lead chalcogenides. We demonstrate that grains can be obtained by taking advantage of the reconstructions along the phase transition path that connects the rocksalt structure to its high-pressure form. Since grain features naturally change as a function of size, they impact thermal conductivity over different length scales. To understand this effect we use a combination of advanced molecular dynamics techniques to engineer grains and to evaluate thermal conductivity in PbSe. By affecting grain morphologies only, i.e. at constant chemistry, two distinct effects emerge: the lattice thermal conductivity is significantly lowered with respect to the perfect crystal, and its temperature dependence is markedly suppressed. This is due to an increased scattering of low frequency phonons by grain boundaries over different size scales. Along this line we propose a viable process to produce hierarchical thermoelectric materials by applying pressure via a mechanical load or a shockwave as a novel paradigm for material design. PMID- 26815915 TI - Host Factors and Biomarkers Associated with Poor Outcomes in Adults with Invasive Pneumococcal Disease. AB - BACKGROUND: Invasive pneumococcal disease (IPD) causes considerable morbidity and mortality. We aimed to identify host factors and biomarkers associated with poor outcomes in adult patients with IPD in Japan, which has a rapidly-aging population. METHODS: In a large-scale surveillance study of 506 Japanese adults with IPD, we investigated the role of host factors, disease severity, biomarkers based on clinical laboratory data, treatment regimens, and bacterial factors on 28-day mortality. RESULTS: Overall mortality was 24.1%, and the mortality rate increased from 10.0% in patients aged ?50 years to 33.1% in patients aged >=80 years. Disease severity also increased 28-day mortality, from 12.5% among patients with bacteraemia without sepsis to 35.0% in patients with severe sepsis and 56.9% with septic shock. The death rate within 48 hours after admission was high at 54.9%. Risk factors for mortality identified by multivariate analysis were as follows: white blood cell (WBC) count <4000 cells/MUL (odds ratio [OR], 6.9; 95% confidence interval [CI], 3.7-12.8, p < .001); age >=80 years (OR, 6.5; 95% CI, 2.0-21.6, p = .002); serum creatinine >=2.0 mg/dL (OR, 4.5; 95% CI, 2.5 8.1, p < .001); underlying liver disease (OR, 3.5; 95% CI, 1.6-7.8, p = .002); mechanical ventilation (OR, 3.0; 95% CI, 1.7-5.6, p < .001); and lactate dehydrogenase >=300 IU/L (OR, 2.4; 95% CI, 1.4-4.0, p = .001). Pneumococcal serotype and drug resistance were not associated with poor outcomes. CONCLUSIONS: Host factors, disease severity, and biomarkers, especially WBC counts and serum creatinine, were more important determinants of mortality than bacterial factors. PMID- 26815916 TI - Access to Treatment for Diabetes and Hypertension in Rural Cambodia: Performance of Existing Social Health Protection Schemes. AB - BACKGROUND: Non-communicable diseases (NCD) pose challenges to Cambodia's health system. Medicines for NCD are on the National Essential Medicines List but no clinical guidelines support their utilization. Two social health protection schemes aimed at the informal sector population exist (Health Equity Funds and Insurance) together with two disease-specific interventions (a Peer Educator Network and Chronic Diseases Clinics) targeted at NCD patients. This study examines performance of these various schemes in relation to NCD. METHODS: Cross sectional household survey among 709 individuals self-reporting diabetes and/or hypertension in three geographical locations in rural Cambodia using a structured questionnaire investigating diagnostic and treatment pathways, health seeking behaviour, health expenditures, and financial coping mechanisms. RESULTS: Two third of respondents with NCD were female and 55% did not belong to any scheme. The majority (59%) were diagnosed in the private sector and only 56% were on allopathic treatment that was mainly sought in the private sector (49%). Outpatient treatment cost was higher in the private sector and when using multiple providers of care. The majority were indebted, 11% due to health-related expenses. Contrary to social health protection schemes, disease-specific interventions offered better access to allopathic treatment and provided medicines in accordance with NEML. CONCLUSION: The benefit packages of existing social health protection schemes and services in the public health sector should be adjusted to cater for the needs of people living with NCD in rural Cambodia. Initiatives that offer active disease management strategies and promote patients and community participation appear more successful in increasing treatment adherence and decreasing the risk of financial hardship. PMID- 26815917 TI - Establishing Age-Adjusted Reference Ranges for Iris-Related Parameters in Open Angle Eyes with Anterior Segment Optical Coherence Tomography. AB - PURPOSE: Define criteria for iris-related parameters in an adult open angle population as measured with swept source Fourier domain anterior segment optical coherence tomography (ASOCT). METHODS: Ninety-eight eyes of 98 participants with open angles were included and stratified into 5 age groups (18-35, 36-45, 46-55, 56-65, and 66-79 years). ASOCT scans with 3D mode angle analysis were taken with the CASIA SS-1000 (Tomey Corporation, Nagoya, Japan) and analyzed using the Anterior Chamber Analysis and Interpretation software. Anterior iris surface length (AISL), length of scleral spur landmark (SSL) to pupillary margin (SSL-to PM), iris contour ratio (ICR = AISL/SSL-to-PM), pupil radius, radius of iris centroid (RICe), and iris volume were measured. Outcome variables were summarized for all eyes and age groups, and mean values among age groups were compared using one-way analysis of variance. Stepwise regression analysis was used to investigate demographic and ocular characteristic factors that affected each iris related parameter. RESULTS: Mean (+/-SD) values were 2.24 mm (+/-0.46), 4.06 mm (+/-0.27), 3.65 mm (+/-0.48), 4.16 mm (+/-0.47), 1.14 (+/-0.04), 1.51 mm2 (+/ 0.23), and 38.42 MUL (+/-4.91) for pupillary radius, RICe, SSL-to-PM, AISL, ICR, iris cross-sectional area, and iris volume, respectively. Both pupillary radius (P = 0.002) and RICe (P = 0.027) decreased with age, while SSL-to-PM (P = 0.002) and AISL increased with age (P = 0.001). ICR (P = 0.54) and iris volume (P = 0.49) were not affected by age. CONCLUSION: This study establishes reference values for iris-related parameters in an adult open angle population, which will be useful for future studies examining the role of iris changes in pathologic states. PMID- 26815919 TI - SPE-UPLC-MS/MS for the determination of phthalate monoesters in rats urine and its application to study the effects of food emulsifier on the bioavailability of priority controlling PAEs. AB - This research was mainly focused on the effects of food emulsifier on the bioavailability of six priority controlling phthalate acid esters (PAEs) for the further accurate assessment of their toxic effects, using the corresponding phthalate acid monoesters (PAMEs) in rats urine as biomarkers. Glycerin monostearate was chosen as typical food emulsifier. A method was established to determine PAMEs in urine from rats either in experimental group (integrated gavaged with glycerin monostearate and PAEs) or in control group (gavaged with PAEs only), by using solid-phase extraction (SPE) coupled with ultra performance liquid chromatography tandem mass spectrometry (SPE-UPLC-MS/MS). Extraction recoveries were more than 75% for all the PAMEs; the calibration curve was linear in the range of 1.0-1000.0ng/mL with R(2)>0.995; the limits of detection (LOD) were 0.30ng/mL-0.50ng/mL. In addition, by analysing quality control (QC) urine samples in 3 days, it showed that the method was precise and accurate, for the intra-day and inter-day RSD within 16%, and the accuracy more than 82%. Internal exposure amount of all PAEs in experimental group was significantly higher than that in control group with p values of less than 0.05 except for butyl benzyl phthalates (BBP) (P=0.07). The bioavailability of all PAEs ranged from 5.03% to 109.35% with the presence of food emulsifiers glycerin monostearate, observably higher than that without glycerin monostearate (1.12% to 54.39%). It indicated that food emulsifiers increased the bioavailability of PAEs and may lead to potential food safety risk, which should bring awareness and be further studied. PMID- 26815920 TI - A robust analytical method for measurement of phytoestrogens and related metabolites in serum with liquid chromatography tandem mass spectrometry. AB - A sensitive and robust method using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed for quantitation of 13 phytoestrogens and related metabolites in rat serum samples. A new type of column, the Kinetex core-shell C18 column, was applied for rapid separation of the target analytes in 10min. Two enzymes, sulfatase H-1 and gulcuronidase H-5 from Helix pomatia were compared on the efficiency of releasing the conjugated forms of the target analytes to their free forms in serum samples. The method detection limit (MDL) defined as three times the signal to noise ratio in spiked serum matrix-based solutions was in the range of 0.1-3.5ng/mL. The linear dynamic calibration was in the broad range of 0.2-500ng/mL for all target compounds. Thirty-two rat serum samples from the rats that were fed with diets containing either casein or soy protein isolates with various amounts of isoflavones for 8 weeks were analyzed for the target analytes with the developed method. Nine target analytes were detected in the serum samples. Those detectable compounds are all the metabolites of the dietary isoflavones, suggesting that the diet isoflavones were mostly metabolized to their metabolites in rat. PMID- 26815921 TI - The Factor Structure of SCL-90 and MCMI Scale Scores: Within-Measure and Interbattery Analyses. AB - This article reports scale-level factor analyses for two widely used self-report measures of psychopathology - the Symptom Checklist-90-R (Derogatis, 1983) and the Millon Clinical Multiaxial Inventory (Millon, 1983) - and compares the obtained factor structures with findings reported in the literature to determine whether each instrument possesses a reliable, meaningful dimensional structure underlying its scale scores. The sample was a heterogeneous group of psychiatric inpatients and outpatients (N = 130). The SCL-90 scale scores formed two highly correlated factors (anxious depression andparanoid thinking), although the scale intercorrelations could be adequately accounted for by a single factor (as in previous reports). The MCMI scale scores formed three factors (anxiousdepression and emotionality, paranoid and manic thinking, and schizoid thinking), of which the first and second were also highly intercorrelated. Supplementary analyses indicated that to a considerable degree the MCMI factor invariance was an artifact of item overlap among the scales. An interbattery factor analysis was then performed to determine whether any common factors could describe the variance shared among the two instruments' subscales. Two interbattery factors were obtained, representing anxious depression and emotionality and paranoid thinking respectively. The two measures, when used separately, appear to offer only limited interpretability of scale profiles, although their combined use appears to permit differentiation between two major symptom configurations. PMID- 26815922 TI - Generation and Objective Rotation of Generalized Learning Curves Using Matrix Language Products. AB - Two SAS macros are presented which perform Tucker's (1966) modified principal components approach to modeling generalized learning curves analysis up to a rotation of the components. The problem of rotation to a psychologically meaningful solution is considered. For example, when analyzing learning data, one may wish to rotate the components to satisfy Tucker's criteria for learning curves. For the modeling of other kinds of change, different rotational criteria may be appropriate. Graphical or hand rotation is often difficult for researchers. By using matrix manipulation languages currently available, it is possible for a researcher to develop a small number of candidate rotated solutions. Three SAS macros are described which determine whether dimensions should be reflected or rotated, perform objective rotations of the factor pattern matrix in line with Tucker's desiderata, and generate corresponding factor scores. PMID- 26815923 TI - Correcting Correlations of Personality Scales for Spurious Effects of Shared Items. AB - Budescu and Rodgers (1981) noted that zero-order correlations of scales which have items in common have spurious components due to the overlapping elements. They proposed a method of adjusting these correlations, to eliminate the spurious component, and applied this method to correct the normative zero-order correlations of the nine original Minnesota Multiphasic Personality Inventory (MMPI) clinical scales. This article draws attention to the fact that Budescu and Rodgers' reliability-corrected formulae were derived under an assumption which is rarely tenable in the context of personality measurement; namely, that scores on two overlapping scales can be viewed (for purposes of the derivation) as sums of standardized scores of subsets of shared items, and of subsets of items uniquely present in each scale. The assumption generally implies new scales that are not linearly related to the original personality scales, and results in reliability corrected correlations that are not relevant to the original scales. In particular, the assumption cannot be justified with respect to MMPI scales. Reliability-corrected formulae are derived which do not make this assumption. These formulae are equivalent to explicitly defined or implied special cases of Bashaw and Anderson's (1967) "General Linear Case" formula. PMID- 26815924 TI - A Procedure for Obtaining Initial Values of Parameters in the RAM Model. AB - An algorithm for obtaining initial values for the minimization process in covariance structure analysis is developed that is more generally applicable for computing parameters connected to latent variables than the currently existing ones. The algorithm is formulated in terms of the RAM model but can be easily extended to model specifications used in other structural equation programs (e.g., LISREL, Joreskog & Sorbom, 1988, or EQS, Bentler, 1989). PMID- 26815925 TI - Weighted Structural Regression: A Broad Class Of Adaptive Methods For Improving Linear Prediction. AB - Given a criterion variable and two or more predictors, applied linear prediction usually entails some form of OLS regression. But when there are several predictors, and especially when these are subject to non-ignorable errors of measurement, applications of OLS methods are often fraught with problems. Weighted structural regression (WSR) methods can mitigate many difficulties through the incorporation of prior structural models into analyses. WSR methods are sufficiently general to include OLS, ridge, reduced rank regression, as well as most covariance structural regression models, as special cases; many other regression methods, heretofore not available, are also included. In this article adaptive forms of WSR are developed and discussed. According to our bootstrapping studies the new methods have potential to recover known population regression weights and predict criterion score values routinely better than OLS with which they are compared. These new methods are scale free as well as simple to compute; they seem well suited to many prediction applications in behavioral research. PMID- 26815926 TI - Henry Felix Kaiser 1927-1992. PMID- 26815927 TI - Development and evaluation of a short-range applicator for treating superficial moving tumors with respiratory-gated spot-scanning proton therapy using real-time image guidance. AB - Treatment of superficial tumors that move with respiration (e.g. lung tumors) using spot-scanning proton therapy (SSPT) is a high-priority research area. The recently developed real-time image-gated proton beam therapy (RGPT) system has proven to be useful for treating moving tumors deep inside the liver. However, when treating superficial tumors, the proton's range is small and so is the sizes of range straggling, making the Bragg-peaks extremely sharp compared to those located in deep-seated tumors. The extreme sharpness of Bragg-peaks is not always beneficial because it necessitates a large number of energy layers to make a spread-out Bragg-peak, resulting in long treatment times, and is vulnerable to motion-induced dose deterioration. We have investigated a method to treat superficial moving tumors in the lung by the development of an applicator compatible with the RGPT system. A mini-ridge filter (MRF) was developed to broaden the pristine Bragg-peak and, accordingly, decrease the number of required energy layers to obtain homogeneous irradiation. The applicator position was designed so that the fiducial marker's trajectory can be monitored by fluoroscopy during proton beam-delivery. The treatment plans for three lung cancer patients were made using the applicator, and four-dimensional (4D) dose calculations for the RGPT were performed using patient respiratory motion data. The effect of the MRF on the dose distributions and treatment time was evaluated. With the MRF, the number of energy layers was decreased to less than half of that needed without it, whereas the target volume coverage values (D99%, D95%, D50%, D2%) changed by less than 1% of the prescribed dose. Almost no dose distortion was observed after the 4D dose calculation, whereas the treatment time decreased by 26%-37%. Therefore, we conclude that the developed applicator compatible with RGPT is useful to solve the issue in the treatment of superficial moving tumors with SSPT. PMID- 26815928 TI - Mixed Sex Effects on the Second-to-Fourth Digit Ratio of Tungara Frogs (Engystomops pustulosus) and Cane Toads (Rhinella marina). AB - Sexual dimorphism in the ratio of digit lengths has been correlated to behavioral, physiological, and morphological traits in a variety of taxa. While sexual dimorphism in the second-to-fourth digit length ratio (2D:4D) is a well established indicator of prenatal androgen exposure in mammals, investigations into the patterns of 2D:4D and the drivers of such variation in other taxa are lacking. We used linear mixed effects models to gain a mechanistic understanding of the factors that drive variation in the scaling relationship between the lengths of the second and fourth digits in two species of anurans: tungara frogs (Engystomops pustulosus) and cane toads (Rhinella marina). We found evidence for sexual dimorphism of the 2D:4D scaling relationship on the front feet of tungara frogs, with female frogs having a larger ratio than males resulting from a relatively longer second digit on females. To our knowledge, this mammal-like pattern of sex differences in digit ratio has not yet been reported for anurans. However, given the reduced number of digits on the front feet of anurans, and uncertainty about which digit was lost during evolutionary history, this apparent sexual dimorphism in the front feet of tungara frogs should be treated with caution. In contrast, we found no evidence of sexual dimorphism in 2D:4D on either the front or rear feet of cane toads. This study highlights ambiguities in 2D:4D across taxa and suggests that further research is needed to evaluate the effect of androgens on 2D:4D in animals other than placental mammals. PMID- 26815929 TI - Intravitreal bevacizumab and feeder vessel laser treatment for a posteriorly located retinal capillary hemangioma. AB - Retinal capillary hemangioma (RCH) is strongly associated with von Hippel-Lindau (VHL) disease. Treatment of this sight-threatening condition is often unsatisfactory despite multiple treatment options available. We here describe an interesting case of a 50-year-old male with RCH located in the perifoveal region of the left eye. Subretinal bleed, exudation, and macular edema resulted in progressive deterioration of visual acuity. Fundus photography, fluorescein angiography, and optical coherence tomography (OCT) were used to serially monitor the lesion. After ruling out systemic lesions of VHL disease, the patient was subjected to direct laser photocoagulation of the lesion which resulted in further loss in vision with increase in bleed and exudation. Subsequently, the patient was given 2 monthly intravitreal injections of bevacizumab followed by laser photocoagulation of feeder arteriole. This combination therapy resulted in resolution of exudation, bleed, and macular edema with improvement in visual acuity. Thus, vision-threatening RCH may be safely and effectively treated by means of a combination therapy comprising of intravitreal bevacizumab and feeder vessel treatment. PMID- 26815930 TI - INCREASING SLEEP DURATION IS ASSOCIATED WITH GEOGRAPHIC ATROPHY AND AGE-RELATED MACULAR DEGENERATION. AB - PURPOSE: Sleeping too much or too little has been associated with adverse health outcomes including total mortality, cardiovascular disease, Type 2 diabetes, and hypertension. This study explored the relationship between sleep patterns and age related macular degeneration (AMD). METHODS: One thousand and three consecutive patients in a retina practice were prospectively surveyed regarding sleep histories. Each patient then had a masked ophthalmic examination and was graded on the modified Wisconsin Age-Related Maculopathy System. The relationship between AMD grade and sleep hours was analyzed in a logistic regression model. Multivariable analysis was performed after adjustment for age, gender, and smoking history. RESULTS: In multivariable analysis, controlling for age, gender, and smoking history, sleep hours are not associated with neovascular AMD (P = 0.97) but are associated with geographic atrophy (P = 0.02). Sleeping >8 hours is associated with geographic atrophy (age-adjusted odds ratio, 7.09; 95% confidence interval, 1.59-31.6) compared with patients without AMD. CONCLUSION: Longer sleep duration is associated with geographic atrophy secondary to AMD. These altered sleep patterns may be another morbidity of AMD, but further study is necessary. PMID- 26815931 TI - THINKING LEAN: Improving Vitreoretinal Clinic Efficiency by Decentralizing Optical Coherence Tomography. AB - PURPOSE: Patients in vitreoretinal clinic have long wait times that could be reduced by improving the efficiency of patient flow. The objective of this study was to determine whether decentralizing optical coherence tomography (OCT) into the technicians' room would reduce patient wait times and improve clinic efficiency. METHODS: Randomized, single-center, clinical trial for 1 month without follow-up at Byers Eye Institute at Stanford. Subjects were return patients of three vitreoretinal specialists in March 2013. The intervention consisted of decentralizing OCT devices from the central photography suite into the technician screening rooms. Total clinic times and total wait times throughout subject appointments were recorded and compared with the control group (centralized photography suite). Secondary outcomes included frequency of injections, procedures, and primary diagnosis codes. RESULTS: Decentralized OCT reduced patient wait times by 74% and reduced total clinic appointment time by 36%. Subjects in the intervention arm experienced significantly reduced total wait time (mean difference = 15.9 minutes, P < 0.0001) and total time in clinic (mean difference = 22.9 minutes, P < 0.0001). CONCLUSION: Decentralized OCT represents the application of lean process concepts to improve vitreoretinal clinic efficiency. Decentralized OCT reduced both the total wait time and total time in clinic for return patients in a vitreoretinal clinic. PMID- 26815932 TI - SYSTEMIC ORAL ANTIBIOTICS AS A PROPHYLACTIC MEASURE TO PREVENT ENDOPHTHALMITIS IN PATIENTS WITH OPEN GLOBE INJURIES IN COMPARISON WITH INTRAVENOUS ANTIBIOTICS. AB - PURPOSE: To compare the use of systemic oral and intravenous antibiotics as a prophylactic measure to prevent endophthalmitis in patients with open globe injuries. METHODS: This prospective study was conducted on 1,255 consecutive patients with open globe injuries due to sharp or blunt trauma in a hospital setting in Tehran, Iran from January, 2011 to May, 2013. The patients were randomly divided into two groups and either received intravenous or oral systemic antibiotics as a measure to prevent endophthalmitis. The patients who developed endophthalmitis were followed for 1 year. RESULTS: In the first group, 12 patients (1.8%) developed endophthalmitis until postoperative Day 3 and 2 more patients (0.3%) developed endophthalmitis until the end of Week 1. These numbers in group receiving oral antibiotics were 8 (1.3%), 5 (0.8%), and 13 patients, respectively, showing no statistically significant difference between the 2 groups. There was also no statistically significant difference in the visual acuity of patients developing endophthalmitis in these 2 groups 1 year postoperatively. CONCLUSION: No statistically significant difference in the occurrence of postoperative endophthalmitis or the visual acuity 1 year after operation among patients with open globe injuries receiving intravenous or oral systemic antibiotics as a prophylactic measure was observed. PMID- 26815933 TI - Size-Tuning Ionization To Optimize Gold Nanoparticles for Simultaneous Enhanced CT Imaging and Radiotherapy. AB - Computed tomography (CT) contrast and radiosensitization usually increase with particle sizes of gold nanoparticles (AuNPs), but there is a huge challenge to improve both by adjusting sizes under the requirements of in vivo application. Here, we report that AuNPs have great size-dependent enhancements on CT imaging as well as radiotherapy (RT) in the size range of 3-50 nm. It is demonstrated that AuNPs with a size of ~13 nm could simultaneously possess superior CT contrast ability and significant radioactive disruption. The Monte Carlo method is further used to evaluate this phenomenon and indicates that the inhomogeneity of gold atom distributions caused by sizes may influence secondary ionization in whole X-ray interactions. In vivo studies further indicate that this optimally sized AuNP improves real-time CT imaging and radiotherapeutic inhibition of tumors in living mice by effective accumulation at tumors with prolonged in vivo circulation times compared to clinically used small-molecule agents. These results suggest that ~13 nm AuNPs may serve as multifunctional adjuvants for clinical X-ray theranostic application. PMID- 26815935 TI - Modulating crystal grain size and optoelectronic properties of perovskite films for solar cells by reaction temperature. AB - Regulating the temperature during the direction contact and intercalation process (DCIP) for the transition from PbI2 to CH3NH3PbI3 modulated the crystallinity, crystal grain size and crystal grain orientation of the perovskite films. Higher temperatures produced perovskite films with better crystallinity, larger grain size, and better photovoltaic performance. The best cell, which had a PCE of 12.9%, was obtained on a film prepared at 200 degrees C. Further open circuit voltage decay and film resistance characterization revealed that the larger grain size contributed to longer carrier lifetime and smaller carrier transport resistance, both of which are beneficial for solar cell devices. PMID- 26815934 TI - The proportion cured of patients diagnosed with Stage III-IV cutaneous malignant melanoma in Sweden 1990-2007: A population-based study. AB - The survival in cutaneous malignant melanoma (CMM) is highly dependent on the stage of the disease. Stage III-IV CMM patients are at high risk of relapse with a heterogeneous outcome, but not all experience excess mortality due to their disease. This group is referred to as the cure proportion representing the proportion of patients who experience the same mortality rate as the general population. The aim of this study was to estimate the cure proportion of patients diagnosed with Stage III-IV CMM in Sweden. From the population-based Swedish Melanoma Register, we included 856 patients diagnosed with primary Stage III-IV CMM, 1990-2007, followed-up through 2013. We used flexible parametric cure models to estimate cure proportions and median survival times (MSTs) of uncured by sex, age, tumor site, ulceration status (in Stage III patients) and disease stage. The standardized (over sex, age and site) cure proportion was lower in Stage IV CMMs (0.15, 95% CI 0.09-0.22) than non-ulcerated Stage III CMMs (0.48, 95% CI 0.41 0.55) with a statistically significant difference of 0.33 (95% CI = 0.24-0.41). Ulcerated Stage III CMMs had a cure proportion of 0.27 (95% CI 0.21-0.32) with a statistically significant difference compared to non-ulcerated Stage III CMMs (difference 0.21; 95% CI = 0.13-0.30). The standardized MST of uncured was approximately 9-10 months longer for non-ulcerated versus ulcerated Stage III CMMs. We could demonstrate a significantly better outcome in patients diagnosed with non-ulcerated Stage III CMMs compared to ulcerated Stage III CMMs and Stage IV disease after adjusting for age, sex and tumor site. PMID- 26815936 TI - Editorial note. PMID- 26815937 TI - EDITORIAL NOTE. PMID- 26815938 TI - Sinos River Hydrographic Basin: urban occupation, industrialization and environmental memory. AB - This article presents an analysis of the process of industrialization and urbanization of the Sinos Valley in Rio Grande do Sul state, Brazil, starting from the establishment of leather goods and footwear manufacturing in the region during the 19th century when tanneries and factories producing footwear and/or components for footwear began to appear, and with special attention to aspects related to the environmental impact on the Sinos river hydrographic basin. The article is based on both bibliographic and documentary research and also draws on biographical narratives of workers with links to the leather goods and footwear industry obtained using ethnographic method. It was found that contemporary environmental conflicts emerge from within a memory of work and an environmental memory in which the factories, the unplanned urbanization, and the utilization of water and other natural resources form a chain of significance. Significance that precludes any form of fragmented analysis that isolates any of these aspects from the others: the economic, socio-historic, cultural, political, or the environmental. PMID- 26815939 TI - Luiz Rau creek and the city of Novo Hamburgo, Rio Grande do Sul. AB - This article presents a reflection on the past and current history, uses, and significance of the Luiz Rau creek to the municipality of Novo Hamburgo, Rio Grande do Sul. Its waters have always been important to the region, quenching the thirst of the local population and their livestock and providing venues for shared social interactions, but also as a destination for municipal industrial and household waste, which has polluted the waters of the creek. Our primary objective is to present and discuss these aspects with the purpose of elucidating the historical importance of this watercourse to the city of Novo Hamburgo. Toward that end, we conducted an exploratory survey to obtain the necessary inputs for such a discussion. We also employed texts from the now-defunct Jornal 5 de Abril and from Jornal NH, the highest-circulating newspaper in the region, to illustrate some situations experienced by the community. We found that municipal waste continues to be dumped into the creek, which has made it rather unloved by the local residents, but it remains firmly present in their daily lives. PMID- 26815940 TI - For an ecology of scientific work: science, politics and the case of streams Pampa and Luiz Rau in Novo Hamburgo, Brazil. AB - If, like Weber writes, every knowledge is objective in terms of evolving the interests of researchers and the agencies, in this article, we investigate that, which has been researched about two streams: Pampa and Luiz Rau. In doing so, in addition to highlighting what has caught the researchers' attention, this paper manages to point out a few gaps and fruitful fields of study which extend beyond the hard sciences. This study is, therefore, characterized as an essay review paper that sets out to use anthropology of science to think about the limitations and advances the studies about the two streams have achieved, as well as their social impact. PMID- 26815941 TI - The river basins of Pirapo, Paranapanema 3 and Paranapanema 4: socioeconomic and environmental aspects. AB - Scarcity of water in the world, virtually, has two sources: the quality and the quantity made available for populations. In the area covered by this study, the selected municipalities from the river basins 3 e 4 of the Paranapanema River and from the basin of the Pirapo River, availability is always greater than the demand and the environmental problems are more often linked to the quality than to the quantity of water. To check the socioeconomic aspects and the daily practices involving water resources and environmental problems we selected a representative sample of families from 10 studied municipalities. The main conclusions point to the existence of key municipalities, regarded as foci of pollution, i. e., the municipalities do not contribute in equal measure to the pollution of rivers from their regions and some stand out in economic activities and inherited cultural practices. However, respondents did not always relate the environmental impacts with their routine and productive activities. Thus, although the new legal environment imposes new practices, there are still cultural heritages, which require more incisive and continuous public interventions. PMID- 26815942 TI - Environmental education for sustainable management of the basins of the rivers Pirapo, Paranapanema III and Parapanema IV. AB - The growing concern about the quantity and quality of water has led managers and researchers from various countries to concentrate efforts in the study, planning and management of watersheds, considered appropriate units for the rational and sustainable management of water resources. This experience report presents results of the Program for Communication, Environmental Education and Social Mobilization, which is part of the project "Monitoring Network of the basins of the rivers Pirapo, Paranapanema III and Paranapanema IV - analysis and monitoring of the hydrological behavior", developed by a multidisciplinary team of researchers and graduate students of the State University of Maringa (Parana, Brazil). The goals of the program were: a) To develop continuing education for teachers of basic education, active in state schools located in the basins studied; b) To raise awareness and to promote training of various local social actors; c) To produce educational and promotional materials for teachers and general community, respectively. The methodology was the action research, on the basis of collaborative work between university researchers and participants of the program. The results evidence that teachers and representatives of different social groups had a limited view of issues related to water resources of their region. Courses, workshops and itinerant exhibitions, beyond teaching aids and promotional material prepared by the group of researchers and graduate students contributed to broaden the view of social actors about watersheds to which they are part, from the perspective of an active, critical and responsible participation focused on sustainable use and management of water resources. PMID- 26815943 TI - Water quality monitoring of the Pirapo River watershed, Parana, Brazil. AB - This study aimed to evaluate the water quality of the Pirapo River watershed in Parana, Brazil, and identify the critical pollution sites throughout the drainage basin. The water quality was monitored during the period from January 2011 to December 2012. Nine points distributed throughout the main channel of the Pirapo River were sampled for a total of 17 samplings. The water quality was evaluated based on the determination of 14 physical, chemical and microbiological parameters. Analysis of the variables monitored in the Pirapo River watershed using factor analysis/principal components analysis (FA/PCA) indicated the formation of three distinct groups of parameters: water temperature (Twater), dissolved oxygen (DO) and a group composed of total suspended solids (TSS), turbidity and nitrite (NO2-). The parameters Twater and DO exhibited a relationship with the seasonality, and the TSS, turbidity, and NO2- levels were correlated with surface runoff caused by rainfall events. Principal component analysis (PCA) of the sampling points enabled the selection of the 10 most important variables from among the 14 evaluated parameters. The results showed that the nitrate (NO3-), NO2-, TSS, turbidity and total phosphorous (TP) levels were related to the soil type, and the parameters DO, electrical conductivity (EC), ammoniacal nitrogen (N-NH3) and thermotolerant coliforms (TC) were related to organic matter pollution, with the P5 sampling site being the most critical site. The ordination diagram of the sampling points as a function of the PCA indicated a reduction from 9 to 5 sampling points, indicating the potential for decreasing the costs associated with monitoring. PMID- 26815945 TI - Flexible Solar Cells Using Doped Crystalline Si Film Prepared by Self-Biased Sputtering Solid Doping Source in SiCl4/H2 Microwave Plasma. AB - We developed an innovative approach of self-biased sputtering solid doping source process to synthesize doped crystalline Si film on flexible polyimide (PI) substrate via microwave-plasma-enhanced chemical vapor deposition (MWPECVD) using SiCl4/H2 mixture. In this process, P dopants or B dopants were introduced by sputtering the solid doping target through charged-ion bombardment in situ during high-density microwave plasma deposition. A strong correlation between the number of solid doping targets and the characteristics of doped Si films was investigated in detail. The results show that both P- and B-doped crystalline Si films possessed a dense columnar structure, and the crystallinity of these structures decreased with increasing the number of solid doping targets. The films also exhibited a high growth rate (>4.0 nm/s). Under optimal conditions, the maximum conductivity and corresponding carrier concentration were, respectively, 9.48 S/cm and 1.2 * 10(20) cm(-3) for P-doped Si film and 7.83 S/cm and 1.5 * 10(20) cm(-3) for B-doped Si film. Such high values indicate that the incorporation of dopant with high doping efficiency (around 40%) into the Si films was achieved regardless of solid doping sources used. Furthermore, a flexible crystalline Si film solar cell with substrate configuration was fabricated by using the structure of PI/Mo film/n-type Si film/i-type Si film/p type Si film/ITO film/Al grid film. The best solar cell performance was obtained with an open-circuit voltage of 0.54 V, short-circuit current density of 19.18 mA/cm(2), fill factor of 0.65, and high energy conversion of 6.75%. According to the results of bending tests, the critical radius of curvature (RC) was 12.4 mm, and the loss of efficiency was less than 1% after the cyclic bending test for 100 cycles at RC, indicating superior flexibility and bending durability. These results represent important steps toward a low-cost approach to high-performance flexible crystalline Si film-based photovoltaic devices. PMID- 26815944 TI - Observed Incidence of Uveitis Following Certolizumab Pegol Treatment in Patients With Axial Spondyloarthritis. AB - OBJECTIVE: Axial spondyloarthritis (axial SpA) is characterized by inflammation of the spine and sacroiliac joints and can also affect extraarticular sites, with the most common manifestation being uveitis. Here we report the incidence of uveitis flares in axial SpA patients from the RAPID-axSpA trial, including ankylosing spondylitis (AS) and nonradiographic (nr) axial SpA. METHODS: The RAPID-axSpA (NCT01087762) trial is double-blind and placebo-controlled to week 24, dose-blind to week 48, and open-label to week 204. Patients were randomized to certolizumab pegol (CZP) or placebo. Placebo patients entering the dose-blind phase were re-randomized to CZP. Uveitis events were recorded on extraarticular manifestation or adverse event forms. Events were analyzed in patients with/without history of uveitis, and rates reported per 100 patient-years. RESULTS: At baseline, 38 of 218 CZP-randomized patients (17.4%) and 31 of 107 placebo-randomized patients (29.0%) had past uveitis history. During the 24-week double-blind phase, the rate of uveitis flares was lower in CZP (3.0 [95% confidence interval (95% CI) 0.6-8.8] per 100 patient-years) than in placebo (10.3 [95% CI 2.8-26.3] per 100 patient-years). All cases observed during the 24 week double-blind phase were in patients with a history of uveitis; in these patients, rates were similarly lower for CZP (17.1 [95% CI 3.5-50.1] per 100 patient-years) than placebo (38.5 [95% CI 10.5-98.5] per 100 patient-years). Rates of uveitis flares remained low up to week 96 (4.9 [95% CI 3.2-7.4] per 100 patient-years) and were similar between AS (4.4 [95% CI 2.3-7.7] per 100 patient years) and nr-axial SpA (5.6 [95% CI 2.9-9.8] per 100 patient-years). CONCLUSION: The rate of uveitis flares was lower for axial SpA patients treated with CZP than placebo during the randomized controlled phase. Incidence of uveitis flares remained low to week 96 and was comparable to rates reported for AS patients receiving other anti-tumor necrosis factor antibodies. PMID- 26815946 TI - A photonic crystal hydrogel suspension array for the capture of blood cells from whole blood. AB - Diagnosing hematological disorders based on the separation and detection of cells in the patient's blood is a significant challenge. We have developed a novel barcode particle-based suspension array that can simultaneously capture and detect multiple types of blood cells. The barcode particles are polyacrylamide (PAAm) hydrogel inverse opal microcarriers with characteristic reflection peak codes that remain stable during cell capture on their surfaces. The hydrophilic PAAm hydrogel scaffolds of the barcode particles can entrap various plasma proteins to capture different cells in the blood, with little damage to captured cells. PMID- 26815947 TI - Structures of Nahuoic Acids B-E Produced in Culture by a Streptomyces sp. Isolated from a Marine Sediment and Evidence for the Inhibition of the Histone Methyl Transferase SETD8 in Human Cancer Cells by Nahuoic Acid A. AB - Nahuoic acids A-E (1-5) have been isolated from laboratory cultures of a Streptomyces sp. obtained from a tropical marine sediment. The structures of the new polyketides 2-5 were elucidated by analysis of spectroscopic data of the natural products and the chemical derivatives 6 and 7. Nahuoic acids 1-5 are in vitro inhibitors of the histone methyltransferase SETD8, and nahuoic acid A (1) and its pentaacetate derivative 8 inhibit the proliferation of several cancer cells lines in vitro with modest potency. At the IC50 for cancer cell proliferation, nahuoic acid A (1) showed selective inhibition of SETD8 in U2OS osteosarcoma cells that reflect its selectivity against a panel of pure histone methyl transferases. A cell cycle analysis revealed that the cellular toxicity of nahuoic acid A (1) is likely linked to its ability to inhibit SETD8 activity. PMID- 26815948 TI - Correction: Alkynyl-functionalized gold NHC complexes and their coinage metal clusters. PMID- 26815949 TI - Boronate affinity molecularly imprinted inverse opal particles for multiple label free bioassays. AB - Boronate affinity molecularly imprinted polymer inverse opal particles were developed for the multiplex label-free detection of glycoproteins with high sensitivity and specificity. PMID- 26815950 TI - Platinum nanozymes recover cellular ROS homeostasis in an oxidative stress mediated disease model. AB - In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide dismutase, catalase, and peroxidase enzymes, with similar or even superior performance than natural enzymes, along with higher adaptability to the changes in environmental conditions. We then exploited their potent activity as radical scavenging materials in a cellular model of an oxidative stress-related disorder, namely human Cerebral Cavernous Malformation (CCM) disease, which is associated with a significant increase in intracellular ROS levels. Noteworthily, we found that Pt nanozymes can efficiently reduce ROS levels, completely restoring the cellular physiological homeostasis. PMID- 26815951 TI - Physician involvement in the care of multiply injured patients: the role of guidelines and subspecialties. PMID- 26815952 TI - Randomized controlled trials affecting polytrauma care. AB - Trauma remains the leading cause of death in the world in patients under 45 years of age. The evaluation, resuscitation, and appropriate management of polytraumatized patients are paramount to successful outcomes. The advance of evidence-based medicine has had a powerful and positive impact on trauma care, even though the nature of many traumatic injuries lends itself poorly to study in a randomized fashion. During the initial management of bleeding patients, hypotensive resuscitation prior to surgical control has found strong support in the literature, and its use has been adopted by many surgeons. Head injury is the most common cause of traumatic death, and while high-level evidence is limited, adherence to management guidelines is associated with improved outcomes. For abdominal trauma, the concept of damage control surgery, while popular, has never been put to the test in a randomized controlled trial. Numerous randomized trials in the field of critical care have affected the management of severely injured patients, including intensive insulin therapy and low tidal volume ventilation in patients with compromised respiratory function. Finally, a multidisciplinary approach to trauma care in designated trauma centers allows for improved outcomes in polytraumatized patients. PMID- 26815953 TI - Impact of trauma societies on the clinical care of polytrauma patients. AB - INTRODUCTION: Trauma societies have an influence on the management and outcome of polytrauma. Its contributions include setting up standard definitions, trauma registries, evidence-based medicine guidelines, and the creation of educational tools such as specific courses of trauma care and decision-making. METHODS: Literature and web-based search of definitions and available information. RESULTS: The history of and accomplishments of trauma societies in the above mentioned domains are reviewed, including the major trauma registries (Major Trauma Outcome Study, National Trauma Data Bank, The American Pediatric Surgical Association, the American Burn Association trauma, and the German Trauma Society trauma registries). Several learned societies in the field of trauma have created recommendations and/or guidelines concerning polytrauma (the Eastern Association for the Surgery of Trauma, The Society of Critical Care Medicine, and the German Trauma Society, Brain Trauma Foundation, and the Essential Trauma Care (EsTC) Guidelines). Several practical, hands-on courses and scoring systems for improving the quality of management of polytrauma patients have been founded and implemented in the past 35 years, including the Advanced Trauma Life Support (ATLS((r))) Course of the American College of Surgeons, the Definitive Surgical Trauma Care (DSTC(TM)) Course, the National Trauma Management Course (NTMC(TM) Course,) the Advanced Trauma Operative Management (ATOM) Course, and the European Trauma Course (ETC). CONCLUSIONS: Trauma and emergency care societies have made an elaborate, substantial contribution by developing trauma registries and creating specific guidelines courses on trauma care and decision-making. PMID- 26815954 TI - The influence of coagulation and inflammation research on the improvement of polytrauma care. AB - Treatment guidelines and management principles of polytrauma patients are largely derived from experience, supplemented by the results of few clinical studies. Their clinical impact on survival outcome is rarely scientifically evaluated. Hence, research algorithms need to be developed which enable a rapid and profound reevaluation of the current treatment strategies in polytrauma care and which provide a solid basis for the assessment of future treatment options. Such new concepts might include a more individualized approach and a better identification of operative windows for early definitive care. Since polytrauma results in a complex physiological and immunological disorder, which is additionally influenced by multiple confounding variables, it is challenging to establish such novel algorithms by clinical research only. In this regard, the well defined parameters in valid basic science models can provide a solid base for evaluating current concepts and investigating future treatment options. Here we have analyzed the contribution of basic science to well-established concepts in polytrauma care, such as the management of trauma induced coagulopathy or the damage control orthopedics concept. Many of these ideas moved from previous basic science activities to clinical studies but in many cases the direct effects of basic science on clinical trials or even clinical management strategies often remain elusive. Nevertheless, the knowledge which is created on a daily basis by basic science studies acts as an invaluable data pool, which can be accessed and combined for the clinical researcher to develop and address clinically relevant questions, providing them with a comprehensive pool of information to carefully plan and conduct their clinical trials. This may then subsequently lead to the development of new management principles for polytrauma patients. PMID- 26815956 TI - Trauma systems: models of prehospital and inhospital care. AB - INTRODUCTION: The organization of trauma care has different perspectives that depend on regional aspects. Among these, geographical peculiarities, historical developments regarding development of medical subspecialties and resident education appear to be the most relevant factors. METHODS: We performed a structured literature search on PubMed. RESULTS AND CONCLUSION: This manuscript deals with the differences of several trauma systems in certain European countries, the USA and Australia. It aims to provide an overview of the peculiarities and influences of these systems on the clinical management. However, the effect of differences in organization in different countries on patient outcome is difficult to assess. There appears to be consensus on the fact that structured treatment for acute trauma care is beneficial for trauma patients. Thus, any kind of organization contributes to improved patient outcome. PMID- 26815955 TI - Technological advancements in the care of the trauma patient. AB - INTRODUTION: Medical technology has benefited many types of patients, but trauma care has arguably benefited more from technologic development than almost any other field. METHODS: A literature review to identify key technological advances in the care of trauma patients was performed. RESULTS: The advances in trauma care are in great measure due to the integration of many different systems. Medical technology impacts care in the field at the site of the trauma, in the transport to trauma facilities, and care at the trauma center itself. Once at the hospital, technology has impacted care in the trauma bay, intensive care units, the operating room, and in postoperative and long-term care settings. The integration of advancements, however, needs to be examined in a careful systematic fashion to insure that patients will actually derive benefit. PMID- 26815957 TI - Patient influx and trauma types in a front-line hospital and a secondary referral hospital after the Wenchuan earthquake: a retrospectively comparative study. AB - PURPOSE: To better understand the differences of patient influx and types of trauma between front-line and referral hospitals after the Wenchuan earthquake, so as to improve the efficiency of injury management. METHODS: A retrospective and comparative study was performed in Deyang People's Hospital (a front-line hospital) and West China Hospital (a secondary referral hospital). RESULTS: A total of 1,106 patients were admitted to the front-line hospital, and 1,775 to the secondary referral hospital. The patient flow peaked within 24 h after the quake, and decreased dramatically thereafter in the front-line hospital, while it peaked 2 days after the disaster in the referral one. Extremities were the most frequent location of all identified injuries (48.4% in the front-line hospital and 49.5% in the second-line hospital). Head and trunk injuries were more frequent in the front-line hospital than the referral hospital. Most of the deaths in the front-line hospital occurred within 24 h (6/8), whilst most in the referral hospital died more than 7 days (29/30) after the earthquake. While the total mortality in the front-line hospital was less than that in the referral hospital (0.7 vs 1.7%), the critical mortality in the former was higher (22.8 vs 9.4%). CONCLUSIONS: There were dramatically different features in terms of quake related patient influx and types of injury between the epicenter and less affected hospitals. PMID- 26815959 TI - The need for early angiography in patients with penetrating renal injuries. AB - BACKGROUND: Renal injuries occur in as many as 10% of penetrating abdominal wounds. Today, these wounds are often managed selectively, but there is little contemporary information on the natural history of kidney injuries after penetrating trauma. The purpose of this study was to examine the clinical outcomes of penetrating injuries to the kidney, and to determine if these patients may benefit from routine early angiography. METHODS: All trauma patients admitted to three Level I Trauma Centers with penetrating renal injuries over a 10 year study period were retrospectively reviewed. RESULTS: We identified 237 patients with a penetrating renal injury, of whom 39 died within the first 24 h and were excluded from analysis. Among the remaining 198 individuals, 130 (66%) underwent immediate exploratory laparotomy. Of the 68 subjects not undergoing immediate surgery, seven had early angiography. The remaining 61 patients (31%) were observed, with 12 (20%) ultimately requiring an intervention to treat the renal injury. Those subjects who failed nonoperative management had significantly fewer hospital-free days compared to those who did not need a procedure (19.2 +/- 8.1 vs. 25.7 +/- 4.5, p = 0.002). CONCLUSIONS: Nearly one in three patients with penetrating renal injuries are currently managed with serial observation, although one in five of these subjects ultimately require either angiographic or surgical treatment. We feel that routine use of early angiography may reduce the failure rate and improve outcomes for patients whose penetrating renal injuries are managed nonoperatively. PMID- 26815958 TI - Splenic injuries: factors affecting the outcome of non-operative management. AB - PURPOSE: The aim of this study was to evaluate the outcome of non-operative management (NOM) in patients with splenic injuries and to determine the predictive factors of NOM failure. METHODS: Two hundred and six patients with splenic injury were admitted between January 2005 and April 2011. Of the 206 patients with splenic injury, 47 patients met the inclusion criteria of NOM. The mechanism of injury, grade of splenic injury, other intra- and extra-abdominal injuries, systolic blood pressure on admission, hemoglobin levels, number of transfusions, Injury Severity Score (ISS), Glasgow Coma Scale score, and hospitalization period were recorded. The patients were divided into two groups: those with NOM and those in whom the failure of NOM led to laparotomy. The patients were monitored for vital signs, abdominal findings, and laboratory data. NOM was abandoned in cases of hemodynamic instability, ongoing bleeding, or development of peritonitis. Independent predictive factors of NOM failure were identified. The patients managed non-operatively were compared with the patients for whom NOM failed. RESULTS: NOM was successful in 40 of 47 patients. There were differences between the two groups for ISS, hemoglobin levels, need for blood transfusion, and the number of associated extra-abdominal injuries. The grade of splenic injury was determined to be an important and significant independent predictive factor for the success of NOM of splenic injuries. CONCLUSIONS: The grade of splenic injury is an important and significant independent predictor factor for the success of NOM. NOM is not recommended in patients with high-grade splenic injury. PMID- 26815960 TI - Limb amputation among patients with surgically treated popliteal arterial injury: analysis of 15 years of experience in an urban trauma center in Cali, Colombia. AB - BACKGROUND: Popliteal arterial injuries carry a high risk of amputation. The currently available literature from both civilian and military experiences is characterized by a wide variation of recommendations for surgical management. We questioned how these recommendations have been applied in our practice. Therefore, we aimed to identify predictors of amputation after popliteal arterial injury. METHODS: We conducted an observational study of 175 patients with popliteal arterial injuries who underwent surgical treatment from 1992 to 2006 at a level I trauma center in Cali, Colombia. Information on demographic characteristics, clinical information, and surgical management was collected from clinical records. The outcome measure was amputation within 30 days following the first surgical intervention. RESULTS: The amputation rate was 17.1%. A multivariable logistic regression model indicates that blunt mechanism (odds ratio [OR] 4.79, 95% confidence interval [CI] 1.49-15.42), signs of ischemia (OR 5.29, 95% CI 1.48-18.91), ligation of the popliteal vein of the compromised limb during surgical exploration (OR 3.83, 95% CI 1.20-12.18), and the development of arterial thrombosis (OR 56.51, 95% CI 12.36-258) were found to be independent predictors of amputation. Fractures, popliteal venous injuries, prolonged time between injury and surgery, fasciotomies, and graft arterial repair were not statistically significant predictors of amputation. CONCLUSIONS: Emphasis on the early assessment and prompt identification of signs of ischemia after popliteal arterial injury continue to be the most important factor for reducing the risk of amputation, especially in blunt trauma. Vascular trauma teams must emphasize the need for the specialized management of popliteal veins. Clinical research is needed in order to identify means of decreasing arterial thrombosis after popliteal repair. PMID- 26815961 TI - Unusual extraperitoneal rectal injuries: a retrospective study. AB - PURPOSE: Rectal injuries, which are rarely encountered because of the anatomic characteristics, occur due to penetrating traumas. In the current study, we aimed to present experiences gleaned from our clinic concerning rarely encountered unusual rectal injuries, including those cases presented for the first time. METHODS: Eleven patients who had been treated for unusual rectal injuries in the General Surgery Clinic of Dicle University between 2004 and 2011 were retrospectively reviewed. RESULTS: The reasons for rectal injuries included foreign bodies in four cases, sexual intercourse in three cases, iatrogenic injuries in two cases, electric shock in one case, and animal horns in one case. All cases had extraperitoneal rectal injuries and all injuries were grade 2 injuries, except for the electrical burn. Primary repair was adequate for the treatment of six patients. Four patients underwent primary repair and ostomy, whereas one of the patients underwent debridement and an ostomy. The patients recovered without complications, except for one patient with sphincter insufficiency. CONCLUSION: The results of the current study suggested that primary repair is adequate in the patients with low-energy injuries and early presentation, whereas an ostomy is required for those with late presentation and for those with high-energy and destructive injuries. PMID- 26815962 TI - Traditional weight-based vancomycin dosing is inadequate in critically ill trauma patients. AB - PURPOSE: Our aim was to evaluate our institution's compliance with weight-based vancomycin dosing recommendations for pneumonia in critically ill injured patients and to assess the success rate in achieving therapeutic serum vancomycin levels. Additionally, we sought to assess the incidence of vancomycin-induced nephrotoxicity. METHODS: All injured intensive care unit (ICU) patients receiving intravenous vancomycin between May 1, 2004 and July 31, 2010 were identified through our trauma database and pharmacy records. The initial weight-based dose was calculated and compared with vancomycin trough levels. RESULTS: Thirty patients were identified who satisfied the inclusion/exclusion criteria. Only 12 patients (40%) received adequate weight-based dosing (weight-based, 30 mg/kg/day). Weight-based patients weighed significantly less than non-weight based patients (62.7 vs. 84.2 kg, p = 0.0008). Weight-based patients were more likely to achieve therapeutic trough levels than non-weight-based patients (58 vs. 33%, p = 0.176). Of patients who achieved therapeutic trough levels, more weight-based patients achieved it at first trough than non-weight-based patients (33 vs. 5.6%, p = 0.046). CONCLUSIONS: When prescribing commonly used dosing regimens, appropriate weight-based administration of vancomycin occurred in only approximately one-third of patients. Those patients who did receive weight-based vancomycin dosing were more likely to achieve therapeutic levels, both initially (33 vs. 5.6%) and overall (58 vs. 33%). PMID- 26815963 TI - Radiation exposure during 3D fluoroscopy of the knee: an experimental study. AB - PURPOSE: To measure the radiation exposure at the knee and surrounding area during the use of 3D fluoroscopy. METHODS: An experimental study was conducted by using a human cadaveric knee as a focus point for the 3D fluoroscope. An isocentric C-arm fluoroscope machine was applied on the lateral side of the knee. The radiation dosage at the focus point and surrounding area was measured. The mean radiation exposure in each location was compared between low- and high resolution scanning. RESULTS: The mean radiation sustained at the focus point was 44.0 +/- 5.6 MUSv and 20.0 +/- 1.0 MUSv in high- and low-resolution scanning, respectively. Radiation exposure on the opposite side of the C-arm machine was found to be higher than that on the other locations with the same distance from the focus point. In low-resolution scanning, radiation could not be detected beyond 75 cm from the focus point at the proximal, distal and same side of the machine. Radiation could be measured at a distance of up to 1.25 m on the opposite side of the machine. In high-resolution scanning, radiation could be measured at a distance of up to 1 m at the proximal, distal and same side of the C-arm, but up to 1.5 m on the opposite side. CONCLUSION: Radiation exposure during 3D fluoroscopy of the knee decreases with increasing distance from the focus point. A higher number of scans in the high-resolution mode causes greater radiation exposure. In isocentric 3D fluoroscopy of the knee, a safe zone is located at least 1.5 m away from the focus point. PMID- 26815964 TI - Etiologic factors in falls from height in pediatric cases. AB - OBJECTIVE: In this study, factors causing falls from height and precautions taken for their prevention were investigated. METHODS: The study was carried out prospectively between June 2009 and June 2010. Patients under 18 years of age presenting at the emergency department of a university hospital, for whom the primary reason for admission was an accidental fall from a height of at least one meter, were included in the study. The demographic characteristics of the patients, the characteristics of the falls, and clinical features were recorded. RESULTS: Data for 133 patients were evaluated. Among these patients, 72 (54.1%) were male; the median age was 4 (IQR 2-7). The most common fall site was a balcony (38%). Falls frequently happened in the spring and the summer. The mean fall height was 2.9 +/- 2.5 m, the median GCS score was 15 (IQR 14-15), and the median PTS was 10 (IQR 9-11). The fall heights was higher in patients who lost consciousness (p < 0.001). Among the 95 patients who were 0-6 years old, it was found that about 55% were unaccompanied by their parents. The most common pathology in the patients was head trauma (63%), while 17.3% had multiple traumas. CONCLUSION: Since the vast majority of the fall cases were in the pre school age group, most were due to falls from a balcony, and more than half of the cases were unaccompanied by parents or caregivers, there are two issues that need to be addressed in relation to pediatric falls from height: family education and legal regulations considering child safety in the design of doors, windows, and balconies of buildings. PMID- 26815966 TI - 31th Meeting of the Pediatric Section of the German Society of Trauma Surgeons (DGU). PMID- 26815965 TI - Lodox/Statscan facilitates the early detection of commonly overlooked extracranial injuries in patients with traumatic brain injury. AB - INTRODUCTION: Traumatic brain injury (TBI) is a common diagnosis in the emergency department. Brain computed tomography (CT) has become a standard diagnostic tool with which to examine TBI patients. Conventional X-rays are ineffective for the evaluation of torso or extremity injuries. In the current study, we attempted to establish a diagnostic modality to evaluate systemically initially unconscious patients in the emergency department with a rapid screening technique characterized by sufficient information, low cost and low radiation exposure. MATERIALS AND METHODS: From January 2008 to December 2009, patients with diminished level of consciousness received the Lodox/Statscan for evaluation of extracranial injuries were enrolled in this study. The accuracy of this diagnostic modality in detecting torso or extremity injuries in initially unconscious patients was analyzed by comparing the initial diagnosis (by the Lodox/Statscan) with the final diagnosis (confirmed by torso CT scan or after two weeks of follow-up). RESULTS: There were 1,210 patients with TBI whose extracranial injuries were evaluated by the Lodox/Statscan. After excluding intra abdominal injuries, the overall sensitivity rates of the Lodox/Statscan in diagnosing torso injuries and extremity injuries were 89.7% and 90.2%, respectively. No long bone fracture was missed by the Lodox/Statscan. The sensitivity and specificity of the Lodox/Statscan in diagnosing long bone fractures were both 100%. Most patients with torso injuries that were missed by the Lodox/Statscan could be managed conservatively without further treatment or complications. All of the missed extremity injuries were distal bone fractures. CONCLUSION: The Lodox/Statscan can provide benefits for surveying extracranial injuries in patients with diminished level of consciousness. The Lodox/Statscan also emits a notably low dose of radiation and appears to be a relatively inexpensive adjunct to screen torso or extremity injuries in TBI patients. PMID- 26815967 TI - European Journal of Trauma and Emergency Surgery : Why the extension of the name? What are the goals? PMID- 26815968 TI - Reconstructive Surgery of Soft-Tissue Defects. PMID- 26815969 TI - Abdominal Wall Reconstruction in a Trauma Setting. AB - According to the World Health Organization "Global burden of disease study", future demographics of trauma are expected to show an increase in morbidity and mortality. In the past few decades, the field of trauma surgery has evolved to provide global and comprehensive care of the injured. While the modern day trauma surgeon is well trained to deal with multitrauma patients with injuries involving several systems, the ever-increasing nature and variety of multitrauma has left lacuna in certain areas. One such area is the management of abdominal wall injuries, which has been the domain of both plastic and reconstructive and general surgeons. The trauma surgeon is adept at treating the contents of the abdomen but not always the container. If not managed properly complications associated with abdominal wall injuries can lead to increased morbidity and mortality. In considering reconstruction of the abdominal wall in multitrauma patients proper evaluation, scrupulous planning, appropriate, and meticulous technique improve the chances for success with minimal complications. In the present article, we provide a brief description of the most commonly used procedures, and more importantly we outline the principles and guidelines applied to abdominal wall reconstruction in order to inform the trauma surgeon of different available treatment options. In doing so, we hope that this review will assist trauma surgeons in their overall care of patients that present with abdominal injuries. PMID- 26815970 TI - Microvascular Reconstruction of the Upper Extremity. AB - BACKGROUND: Upper extremity composite tissue defects may result from trauma, tumor resection, infection, or congenital malformations. When reconstructing these defects the ultimate objectives are to provide adequate soft tissue protection of vital structures, and to provide optimal functional and esthetic outcomes. The development of clinical microsurgery has added a large number of treatment options to the trauma surgeon's armamentarium - primarily replantation of amputated tissues and transplantation of vascularized tissues from distant donor sites. Since the early 1970s, considerable refinement in microsurgical tools and techniques together with a better understanding of the anatomy and physiology of microcirculatory tissue perfusion led to the introduction of a variety of thin, pliable and versatile-free flap designs. METHODS: Sources for this manuscript include a comprehensive literature search using the PUBMED and EMBASE databases along with relevant text books, Selected Readings in Plastic Surgery((r)), and personal experiences of upper extremity reconstruction and microsurgery. RESULTS: In this manuscript, we describe the primary microsurgical techniques used to reconstruct upper extremity tissue defects and discuss the basis for selecting one technique over another. CONCLUSION: Where possible, the best results may be achieved by reattaching the amputated original tissues (microsurgical replantation). In noninfected, uncontaminated traumatic injuries resulting in composite soft tissue defects, Early free flap reconstruction of the upper extremities has important advantages over delayed (72 h-3 months) or late wound closure (3 months-2 years). In recent years, thin, pliable, and versatile fasciocutaneous flaps such as the anterolateral thigh (ALT) and lateral arm (LA) free flaps have been increasingly used with great success to reconstruct the upper extremity. The use of "spare parts" and functional reconstructions using osteomyocutaneous free flaps or toe to thumb transfers complete the armamentarium of the upper limb reconstructive microsurgeon. PMID- 26815971 TI - Reconstruction of Lower Extremity Fractures with Soft Tissue Defects. AB - Reconstruction of osseous and soft tissue defects after high-energy lower extremity trauma remains a challenge in trauma surgery. An initial planning of the reconstruction management is crucial in the therapeutic concept of these severe injuries. In Gustilo type II and IIIa fractures with minimal contamination a primary definite osseous stabilization by internal fixation along with primary soft tissue reconstruction is preferable. A variety of local, regional, and even free microvascular flaps are available for acute wound closure in such cases. Staged reconstruction with initial external fixation and vacuum-assisted wound closure is recommended for severe contaminated wounds and extended defects. Early secondary osseous reconstruction of larger osseous defects can be performed either by distraction lengthening technique or by a free vascularized bone graft. Early secondary soft tissue reconstruction necessitates a wide therapeutic repertoire in order to plan the optimal individual strategy. With a modern therapeutic strategy limb salvage with an adequate function after reconstruction of lower extremity fractures with soft tissue defects can be achieved in the majority of patients. PMID- 26815972 TI - Literature on the Subject of Vacuum Therapy Review and Update. AB - INTRODUCTION: Today, vacuum therapy can be regarded as established in routine clinical use. Many hundreds of reports on the subject of vacuum therapy have appeared in medical literature. This review intends to give an overview of the peer-reviewed literature published to date and its quality considering criteria of evidence-based medicine (EbM). METHODS: Literature search (MEDLINE, EMBASE, Cochrane, extensive manual search); up to May 31, 2006; evidence level: Classification of the Oxford Centre for Evidence-based Medicine. RESULTS: Five hundred and fifty peer-reviewed citations were identified. Impressive jump in the annual publication rate is found from the year 2000 onwards; continuous broadening of the fields of indications; over 85% of all reports are case reports/series (only n = 27; EbM level < 4). To date, most of the publications are by authors from the United States, Germany, United Kingdom, Austria, the Netherlands, Switzerland, France, and Sweden. 7.5% of all peer-reviewed articles investigate scientific back grounds. DISCUSSION: The clinical significance of this therapy is underlined by an obviously continuously marked extension of the range of indications in all surgical fields, and even in extreme ages of the patients. There is a considerable deficit of basic pathophysiological research and well-designed studies. This "deficiency," however, when judged against the quality of the general medical literature, does not point to the poor efficacy or low benefit of vacuum therapy but should rather be seen as a symptom of the clinical practitioner's problems in dealing with modern aspects of the theoretical background of EbM. PMID- 26815973 TI - Magnet Resonance Angiography versus Conventional Angiography for the Planning of Reconstructive Surgeries. AB - Assessing the vascular status and anatomy of the lower extremity is of crucial importance when planning the coverage of a tissue defect with a free flap. The standard techniques comprise the clinical examination, Doppler ultrasound and Doppler sonography for healthy patients without suspected direct trauma to the vascular system, and conventional digital subtraction angiography (DSA), respectively, in case of traumatized vessels or patients with peripheral arterial obstructive disease. MATERIALS: We have conducted a prospective study for the comparison of the magnetic resonance angiography (MRA) to the conventional DSA. Fourteen patients were examined presurgically by means of both a conventional DSA and an MRA before undergoing planned microvascular coverage of tissue defects of the lower extremity. The surgeon, based on a questionnaire, assessed and compared both examination results according to their information content. Furthermore, the presurgically planned level and localization of the vascular anastomoses and the intraoperative findings were compared postoperatively. RESULTS: The MRA examination yielded sufficient information on the vascular anatomy to enable the surgeon to carry out a detailed presurgical planning. Additionally, the use of MRA showed clear advantages with regard to both patient and user comfort. CONCLUSION: Taking into account the advantages for the assessment of vessels using MRA, in particular when considering the impact of the frequently varying vascular anatomy of the lower leg on reconstructive surgery, as well as the significantly lower morbidity rate of the examination itself, then the MRA must be regarded as a safe alternative to the DSA. PMID- 26815974 TI - Predictors of Death in Trauma Patients who are Alive on Arrival at Hospital. AB - OBJECTIVE: To determine which factors predict death occurring in trauma patients who are alive on arrival at hospital Design Prospective cohort study Method Data were collected from 507 trauma patients with multiple injuries, with a Hospital Trauma Index-Injury Severity Score of 16 or more, who were initially delivered by the Emergency Medical Services to the Emergency Department of the University Medical Centre Utrecht (UMCU) during the period 1999-2000. RESULTS: Univariate analysis showed that every year of age increase resulted in a 2% greater risk of death. If the patient had been intubated at the scene of the accident, this risk was increased 4.3-fold. Every point of increase in the Triage Revised Trauma Score (T-RTS) reduced the risk of death by 30%. A similar (but inverse) tendency was found for the HTI-ISS score, with every point of increase resulting in a 5% greater risk of death. There was a clear relationship between the base excess (BE) and hemoglobin (Hb) levels and the risk of death, the latter being increased by 8% for each mmol/l drop in BE, and reduced by 22% for each mmol/l increase in Hb. The risk of death occurring was 2.6 times higher in cases with isolated neurotrauma. These associations hardly changed in the multivariate analysis; only the relation with having been intubated at the scene disappeared. CONCLUSION: The risk of severely injured accident patients dying after arriving in hospital is mainly determined by the T-RTS, age, presence of isolated neurological damage, BE and Hb level. Skull/brain damage and hemorrhage appear to be the most important causes of death in the first 24 h after the accident. The time interval between the accident and arrival at the hospital does not appear to affect the risk of death. PMID- 26815975 TI - Improved Data Quality by Pen Computer-Assisted Emergency Room Data Recording Following Major Trauma in the Military Setting. AB - INTRODUCTION: The characteristics of combat injuries differ from those of injuries encountered in civilian practice. Capturing detailed combat casualty data is therefore of importance. Experts classify the data sources for combat injuries as "inadequate" and request a better and more accurate record keeping. Within the civilian setting it has been shown that "point of care - computer assisted" recording techniques are superior to conventional "paper-based" data recording techniques regarding accuracy of data recording. Subject of this study is to proof the quality of a "point of care - computer-assisted" data recording technique within a "military setting". METHOD: Prospective emergency room study at the multinational-staffed German Field Hospital Kabul/Afghanistan. A standardized emergency room data recording - using "TraumaWatch" - was performed parallel to the emergency room procedures; in each patient a tablet-PC-based technique ("pen group") as well as a traditional paper-based technique ("paper group") was used simultaneously by two nurses of the emergency room team. Data quality was defined as level of dataset completeness. RESULTS: During a 3-month study period, a total number of 171 major trauma cases underwent emergency room management. There was no correlation between degree of injury severity and level of dataset completeness. Total dataset completeness was significantly higher within the "pen group" (93.9 +/- 15.5% vs. 50.1 +/- 21.8%; p < 0.01); the same applies to the core dataset (Utstein style) completeness (94.8 +/- 15.1% vs. 48.9 +/- 18.7%; p < 0.01). CONCLUSION: Defining data quality as level of dataset completeness, a tablet-PC-based recording technique, which allows easy and fast - real-time - data acquisition during emergency room management, seems to be superior to the conventional paper-based technique - even under the conditions of a military mission. PMID- 26815976 TI - An in Vivo Experimental Comparison of Stainless Steel and Titanium Schanz Screws for External Fixation. AB - OBJECTIVE: To compare the clinical benefits of stainless steel (SS) to titanium (Ti) on reducing pin track irritation/infection and pin loosening during external fracture fixation. METHODS: A tibial gap osteotomy was created in 17 sheep and stabilized with four Schanz screws of either SS or Ti and an external fixation frame. Over the 12 week observation period, pin loosening was assessed by grading the radiolucency around the pins and measuring the extraction torque on pin removal at sacrifice. Irritation/infection was assessed with weekly clinical pin track grading. A histological analysis of the tissue adjacent to the pin site was made to assess biocompatibility. RESULTS: A statistically non-significant trend for less bone resorption around Ti pins was found during the early observation period. However, at sacrifice, there was no difference between the two materials. Also, there was no difference in the extraction torque, and there was similar remodeling and apposition of the bone around the pins. A statistically non significant trend for more infection about SS pins at sacrifice was found. Histology showed a slightly higher prevalence of reactionary cells in SS samples, but was otherwise not much different than around Ti pins. CONCLUSIONS: There is no clinically relevant substantial advantage in using either SS or Ti pins on reducing pin loosening or pin track irritation/infection. PMID- 26815977 TI - Anatomical Course of the Superficial Branch of the Radial Nerve and Clinical Significance for Surgical Approaches in the Distal Forearm. AB - 10 embalmed cadaver forearms and wrists were dissected to determine the anatomical course of the superficial branch of the radial nerve in the distal forearm. The superficial radial nerve bifurcated in two branches at a mean of 54,7 mm proximal to the radial styloid. From the styloid process of the radius, the mean distance to the closest dorsal branch of the superficial radial nerve was 3,5 mm and the mean distance to the closest volar branch was 9,8 mm. The mean distance between the closest branch of the superficial radial nerve and Lister?s tubercle was 16,4 mm. The crossing point between the nerve and the cephalic vein was located at a mean of 54,3 mm proximal to the styloid process. At the level of styloid process the mean distance between the closest dorsal branch of the superficial radial nerve and the first dorsal compartment was 15,2 mm and between the closest volar branch and the first dorsal compartment 4,4 mm. Detailed knowledge of anatomic characteristics of the superficial branch of the radial nerve may help prevent injury during operations and treat traumatic lesions of the nerve. Because of great variations in the course of the superficial radial nerve we could not define an absolute safe zone for surgical procedures on the distal forearm. Iatrogenic lesions of the superficial radial nerve are described complications of percutaneous procedures. Therefore open surgical approaches are recommended. PMID- 26815978 TI - The Kashmir Earthquake Experience. AB - On October 8, 2005, a major earthquake measuring 7.6 on the Richter scale struck the Himalayan region of Kashmir. Around 90,000 people died in the mass disaster. The Bone and Joint Hospital in Kashmir found itself in a relatively unique situation of having to deal with the orthopedic morbidity generated by this quake. The hospital received 468 patients over a period of 10 days, out of which 463 were received over the initial 5 days. The admission for a single day peaked at 153 patients on the third day. Due to the unprecedented admission in terms of numbers the hospital utilized outreach methods to streamline admission by sending out specialists to the affected areas. Manpower was judiciously utilized to concentrate specialist advise where required. Besides documenting the pattern of trauma, this paper throws light on some unforeseen problems faced in dealing with a large number of patients far exceeding the normal capacity of the hospital. PMID- 26815979 TI - Function Versus Position: A Randomized Controlled Trial of Interfocal Kirschner Wiring of Unstable Distal Radial Fractures. AB - INTRODUCTION: A randomized, prospective study has been carried out to determine if immobilisation in dorsiflexion following K-wire fixation of unstable distal radial fractures improves functional outcome. METHODS: Sixty patients with unstable fractures of the distal radius were entered into the trial. There were 52 female and 11 male with an average age of 60yrs (17-84). Randomisation was undertaken in theatre using a closed envelope system. The fractures were initially reduced by closed manipulation and interfocal percutaneous K-wires inserted. Patients randomised to group I had their wrists placed in 30 degrees of dorsiflexion and group II had their wrists placed in 30 degrees of palmer flexion. Patients were reviewed with an x-ray at 1, 3, 5, and 17 weeks by a single physician. Dorsal angulation, Radial inclination, Radial length and Radial height were measured. The K-wires were removed in the outpatient clinic at 3 weeks and the plaster at 5 weeks. Blinded functional review was carried out by an Occupational therapist at 5, 8 and 17 weeks post operation. The power and pinch grip was measured using a Jamar dynamometer. Flexion and extension were measured with a goniometer. RESULTS: There was no statistical difference in radiological or functional outcomes in either group. At 17 weeks the mean dorsal angulation was -0.5 and -1.9 degrees. The mean radial shortening was 1.5mm in both groups. The power grip was 86% and 82% and pinch grip was 99% and 101%. Patients regained 76% and 79% of flexion and 94% and 88% of extension compared to the opposite side. CONCLUSIONS: Immobilisation in dorsi-flexion following K-wiring for unstable distal radial fractures does not improve functional outcome. The overall functional results were excellent and we believe that Kwiring still as a place in the treatment of distal radial fractures in the previously defined population. PMID- 26815980 TI - Massive Rectal Hemorrhage from the Middle Hemorrhoidal Artery after Blunt Perineal Trauma Without Pelvic Fracture. AB - BACKGROUND: Severe pelvic hemorrhage after blunt trauma without bony fracture has been reported occasionally, and clinical presentation as a delayed massive rectal bleeding is very rare. CASE STUDY: The case of an 86-year-old woman with massive rectal bleeding 12 h after mild blunt perineal trauma is presented. Physical examination revealed an extensive perineal hematoma and a 2-cm laceration in the posterior rectal wall. Pelvic CT scan revealed a large mesorectal hematoma causing extrinsic compression of the rectal lumen. No bony fracture was observed. Selective arteriography was then performed showing hemorrhage resulting from the right middle hemorrhoidal artery, branch of the internal pudendal artery. Transcatheter embolization of coils successfully controlled the bleeding. However, the patient developed a respiratory distress syndrome and renal failure with no response to the treatment and she died 3 days later. CONCLUSION: This report is unique not only for the unusual association of pelvic hemorrhage and rectal injury after blunt trauma without pelvic fracture but also because of the clinical presentation as a massive rectal bleeding. Undoubtedly, the delayed diagnosis and treatment, 12 h after the trauma, contributed to the fatal outcome. PMID- 26815981 TI - Facial Fractures in Kajang Hospital, Malaysia: A 5-Year Review. AB - OBJECTIVE: The objective of this study was to determine the demographic data as well as other relevant data pertaining to the management of patients with maxillofacial injury in a Malaysian government regional hospital. STUDY DESIGN: Medical records of 313 patients who sustained maxillofacial injury treated in Kajang Hospital, Selangor, Malaysia over a 5-year period (1998-2002) were collected. Data regarding age, gender and race, etiology of injury, site of injury, other associated injuries and treatment undertaken were analyzed. RESULTS: Two hundred and forty-nine male (79.6%) and 64 female patients (20.4%) were treated for maxillofacial trauma. The patients' age range from 1 to 67 years old, with a median age of 23 years old. A high number of Malays (60.1%) sustained maxillofacial injury, followed by Indians (16%), Chinese (13.4%) and other races (10.5%). Road traffic accident was the main etiology for maxillofacial injury with 230 cases (73.5%), followed by fall (16.6%), assault (5.4%), industrial accident (2.6%), sports injuries (0.6%) and others (1.3%). Mandibular fractures were the most common, occurring in 83.1% of the cases while the midfacial fractures accounted for 16.9%. Majority of patients were treated with closed reduction and intermaxillary fixation (88.1%) and 11.9% underwent open reduction and internal fixation. CONCLUSION: Road traffic accident involving motorcyclists was the main cause of maxillofacial trauma in Malaysia. The most common facial fracture was the mandibular fracture. Non-surgical manipulation of fracture was the most common treatment carried out in this hospital. PMID- 26815982 TI - Mid-Anterior Tibial Stress Fracture in a Female Elite Athlete : A Case Report. AB - We report the case of an unusual tibial stress fracture and its successful surgical treatment in a female elite sprinter 2 years after complete consolidation of the same tibia following resection of an osteoid osteoma. PMID- 26815983 TI - Dorsal Double-Plate Fixation of the Distal Radius. AB - OBJECTIVE: Restoration of the intra- and extraarticular anatomy of the distal radius. Stable internal fixation of fragments, with the possibility of early functional rehabilitation. INDICATIONS: Distal intraarticular radius fractures with impacted articular fragments and displaced dorsoulnar fragment. Distal intraarticular radius fractures with bony or ligamentous injury of the proximal carpal row. CONTRAINDICATIONS: General medical contraindications for surgical intervention. Distal radius fractures with palmar tilt of the distal fragment. SURGICAL TECHNIQUE: Dorsal longitudinal incision. Approach to the intermediate column via the third extensor compartment by detaching the extensor pollicis longus (EPL) tendon. Arthrotomy and revision of the proximal carpal row. Reconstruction of the radiocarpal articular surface and support with a plate applied to the dorsoulnar aspect. Approach to the radial column by subcutaneous preparation between skin flaps (cave: superficial branch of the radial nerve) and retinaculum, incision of the first extensor compartment and support of the radial column with a preshaped plate, which is pushed through under the tendons of the first compartment. Cancellous bone grafting is usually not necessary. Subcutaneous displacement of the EPL tendon with the aid of a small retinacular flap. POSTOPERATIVE MANAGEMENT: Application of a removable velcro cuff. Immediate functional postoperative physiotherapy, without the cuff. No straining or forcing until first radiographic examination at 6 weeks after the operation. RESULTS: 25 consecutive patients were monitored following a double-plate fixation, with a minimum follow- up of 12 months. In all cases the reduction, in accordance with the Stewart Score, was very good, a loss of reduction was not observed. The range of motion was between 100 degrees and 160 degrees for flexion/extension and between 160 degrees und 180 degrees for pronation/supination. The average DASH Score was 7.2 points, the PRWE Score 8.0 points. No relevant loss of strength (JAMAR dynamometer) was found in any of the patients in comparison with the healthy side. Complications noted were a muscle adhesion in the region of the first extensor compartment as well as a mild reflex sympathetic dystrophy, which healed without consequences. Implants were removed from six of the patients. PMID- 26815985 TI - Welcome to This First Section of EJTES Especially Devoted to Disaster and Military Surgery! PMID- 26815984 TI - A Challenge between Trainee Education and Patient Safety: Does Fellow Participation Impact Postoperative Outcomes Following Bariatric Surgery? AB - BACKGROUND: Surgical training may potentially influence patient care. A safe, high-quality bariatric and metabolic surgery practice requires dedicated and specialized training commonly acquired during a fellowship. This study evaluates the impact of fellow participation on early postoperative outcomes in bariatric surgery. METHODS: From the American College of Surgeons (ACS-NSQIP) database, we identified all obese patients who had undergone primary laparoscopic Roux-en-Y gastric bypass (LRYGB) and sleeve gastrectomy (LSG) between 2010 and 2012. Logistic regression was used to prognosticate the surgical fellow (PGY-6, 7, or 8) participation in bariatric surgeries on perioperative outcomes, as compared to surgeries with no trainee participation. RESULTS: The study cohort consisted of 10,838 patients (8819 LRYGB, 2019 LSG, 32 % fellow participation). Fellows participated in higher-risk surgeries. Fellow involvement was associated with increased operative time in LRYGB (difference 42.4 +/- 1.2 min, p < 0.001) and in LSG (difference 38.8 +/- 2.5 min, p < 0.001). Multivariate regression revealed that fellow involvement in LSG did not significantly alter postoperative adverse events. Conversely, in the LRYGB group, fellow participation was independently associated with higher rates of overall complications (OR = 1.37, 95 % CI 1.16 1.63), serious complications (OR = 1.23, 95 % CI 1.00-1.52), surgical complications (OR = 1.42; 95 % CI 1.17-1.73), and reoperation (OR = 1.43, 95 % CI 1.10-1.87). On adjusted analysis, while readmission was higher with fellow involvement in both procedures, mortality rates were comparable. CONCLUSIONS: Fellow involvement resulted in a clinically appreciable increase in operative times. Fellow participation in the operating room was also independently associated with worse early postoperative outcomes following LRYGB, but was not the case for LSG. Promoting proficiency in surgical simulation laboratories and a gradual participation of fellows from LSG to LRYGB during fellowship may be associated with a reduction in postoperative complications. PMID- 26815986 TI - Triage: Principles and Pressures. AB - The aim of this paper is to review the art and science underpinning the application of effective triage. The paper also attempts to cut through the fog of confusion surrounding the topic and to point a way towards a generally-agreed unified approach. Triage needs to be understood in the context of the environment in which it is applied, and the paper deals with this in some detail. PMID- 26815987 TI - Overall Asessment of the Response to Terrorist Bombings in Trains, Madrid, 11 March 2004. AB - OBJECTIVES: To provide an overall assessment of the response to the terrorist bombings in Madrid, 11 March 2004, which were considered the deadliest terrorist attack on European soil in modern times. MATERIALS AND METHODS: Overall data on the number of victims treated at the scenes and at primary care facilities and hospitals, as well as the logistics involved, were reported by the EMS and the Health Authority of the Comunidad de Madrid local government. Data were mainly obtained by retrospective chart review, and did not include casualties who had only emotional shock, superficial bruises or transient hearing loss from barotraumas without eardrum perforation. We defined as critical any casualty with an Injury Severity Score (ISS) >15. RESULTS: Over 70,000 personnel were mobilized in the care of the victims. EMS response and total evacuation times at the four blast scenes averaged 7 and 99 min, respectively. There were around 2,000 casualties, and a typical bimodal distribution of deaths, with 177 immediate fatalities and 14 subsequent in-hospital deaths. Almost 60% of casualties were taken to the two closest hospitals. Problems related to security, identification of casualties and record-keeping were encountered at the closest hospital. Closed doors increased the immediate fatality rate in the trains. Most survivors had noncritical injuries, but 14% of the 512 casualties assessed had an ISS >15. The critical mortality rate was 19.5%. The most frequently injured body regions were the head/neck and face. In all, 124 major surgical interventions were performed on 82 victims in the first 24 h, and orthopedic trauma procedures accounted for 50% of the case load. Most patients with lung injuries from the blasts required intubation and mechanical ventilation, and their survival rate was 88.3%. Also, 35% of laparotomies were either negative or nontherapeutic. CONCLUSION: There was a rapid EMS response and evacuation, but also overtriage, uneven distribution of casualties and difficulties in communication. The sizes and resources of the closest hospitals, as well as the early hour, were probably decisive in the adequacy of the overall response. PMID- 26815988 TI - Preparedness of German Paramedics and Emergency Physicians for a Mass Casualty Incident: A National Survey. AB - OBJECTIVE: Paramedics and physicians are important components of our emergency medical system. To date, no survey has been carried out assessing physicians and paramedics regarding their preparedness for a mass casualty incident (MCI) resulting from a terrorist attack in Germany. The aim of this study was to assess the current state of preparedness of emergency physicians and paramedics for an MCI. MATERIALS AND METHODS: Using an online questionnaire, we interviewed 1,707 emergency physicians and paramedics in Germany. The replies were analyzed statistically with the one-way analysis of variance (ANOVA) test and the Tukey Kramer multiple comparisons test. RESULTS: In all, 95% of the emergency physicians and paramedics knew their area of responsibility in the case of an MCI. However, 45% of them were unaware of injury patterns and treatment strategies in patients following nuclear, chemical or biological contamination. Of the interviewed emergency physicians and paramedics, 97% asked for further specific training for MCI/terrorism attacks. CONCLUSIONS: Emergency physicians and paramedics are still insufficiently prepared for nuclear, chemical, and biological as well as conventional terrorism attacks. The emergency training of emergency physicians and paramedics must be modified to accommodate the increased risk of catastrophes and terrorist attacks. PMID- 26815989 TI - Mass Casualty Event During a Musical Parade: Lessons Learned. AB - OBJECTIVE: In the Netherlands, major incidents are sparse, and so there is a general feeling of a relatively low risk. Upon evaluating multiple casualty events (MCEs) in the Netherlands over the last 60 years, it is worth noting 39 major events. Our objective was to report the experiences from a mass casualty incident in an urban area, performing a critical evaluation of the response and outcome related to the scenario in order to learn from our past and to train for the future. MATERIALS AND METHODS: In a retrospective patient record analysis we collected all of the data concerning an MCE we encountered in August 2006. RESULTS: There were 21 casualties at the scene. Of our 19 patients, 12 were seen in the crash room. The average age of the patients was 30 years (range 22-53). In all, 87 X-rays, 1 ultrasound and 15 CT scans were performed. Four patients were admitted: ten patients received definitive wound treatment in the ED. Psychological support was given to all patients. One patient died three days later. CONCLUSION: Triage supported by one person and two trauma teams worked well. The amount of over- and undertriage was in line with the literature. Numbering the patients worked well but also caused enormous problems with the supporting facilities. Centralizing the trauma care yielded certain advantages; however, we must respect our surge capacity of 20 patients. When the number of patients surpasses 20, an alternative plan must be followed. This event has been an eye-opener for our organization; it has given us new tools to prepare for a potential new disaster. PMID- 26815990 TI - Wound Complications from the Tsunami Disaster: A Reminder of Indications for Delayed Closure. AB - OBJECTIVES: To illustrate the character, clinical course and late complications of wounds caused by high energy with severe contamination during a natural disaster, as a basis for designing principles for primary treatment under these conditions. PATIENTS AND METHODS: This paper presents case reports from complicated wounds treated at a specialized unit for wound management in a hospital receiving patients after transfer from primary to definitive treatment. RESULTS: Of the Swedish citizens evacuated from the disaster zone in Thailand after the tsunami disaster in 2004, 174 of those arriving at Stockholm Airport were referred to the Karolinska Hospital for treatment, of whom 75 were admitted. Forty of the patients admitted were seen by the surgeons at the Department of Plastic and Reconstructive Surgery because of complicated wounds requiring special treatment. Fifteen of these could be treated as ambulatory patients and 25 required hospitalization for a mean time of 10.5 days (range 1-48). The majority had multiple injuries, 93% on the lower limbs and 47% on the upper limbs. The majority had been primarily closed at primary treatment. Treatment strategies included removal of all sutures, wound excision, secondary healing (38/40, 95%), delayed primary closure (40/40, 100%), vacuum-assisted closure (VAC) (3/40, 8%), splitthickness skin grafts (23/40, 58%), pedicled perforator flap (1/40, 2%) and free flap (1/40, 2%). Amputation was requested in two cases. Aside from long-lasting psychological sequelae and varying degrees of physical disability, unusual late infections occurred with progressing and migrating abscesses. Cultures and skin biopsies from these revealed both mycobacteria and pigmented fungal hyphae. CONCLUSIONS: The patterns of injury and clinical courses in these patients illustrate the risk of complications in wounds caused by high energy, with severe contamination and which arrive late for primary treatment by staff who are not fully aware of the risk of secondary complications under these conditions. Recommendations for primary treatment should include extensive cleaning, excision of dead tissue and delayed primary closure, according to the well-established principles of management of war wounds, where the conditions are similar. PMID- 26815991 TI - Evaluation of the Response of the Swedish Healthcare System to the Tsunami Disaster in South East Asia. AB - OBJECTIVES: When the tsunami in South East Asia hit the coast of Thailand on December 26, 2004, approximately 20,000 Swedish tourists were in the disaster zone. Of these, 548 died or were lost and more than 1500 were injured. The aim of this study was to evaluate the response of the Swedish health care system to the disaster in terms of assessment and support in the disaster zone, evacuation back to Sweden and continued treatment in Sweden. METHODS: The evaluation was carried out based on (1) structured questionnaires to the staff of Thai hospitals, injured Swedish citizens and Swedish voluntary workers in the disaster zone; (2) semi-structured interviews with representatives of involved authorities, regional health care centres in Thailand and Sweden, hospital command centres, individuals treated for injuries and volunteer workers involved with supporting the injured; (3) on-site visits in the disaster zone; (4) analysis of reports following the tsunami. RESULTS: A total of 11,000 injured were treated during the first 3 days following the tsunami at the six major hospitals in the Phang Nga, Phuket and Krabi provinces where the majority of the Swedish citizens were primarily taken care of. Of these 11,000, 3000 required hospital admission against a total bed capacity of 1400. Almost 1500 surgical operations were performed during the first 3 days across 33 operating theatres. Thai health care representatives and staff confirmed the requirement for teams from countries with many tourists in the area for practical and psychological support, interpretation, assessment for evacuation and undertaking early evacuation to home nations to release local health care resources. This need was also supported by the injured. Sweden, having the highest number of injured citizens next to the host country, was very late compared to other countries in sending assessment teams to the area and in supplying the needed support. CONCLUSIONS: With increased international travelling, many countries today have large numbers of their citizens in other parts of the world. For Sweden, this has been estimated to be 400,000 at any one time, often in areas known to be risk zones for natural disasters and terrorism. This fact of modern-day life demands welldesigned plans to support both citizens in the area and the local health care in several ways: non-medical support by mediating contact between injured and local medical staff, psychological and practical support, support in evacuating own citizens from the area to release local health care and (under specific conditions) medical support. This planning has to include prepared assessment teams that can be rapidly deployed to the scene and a command structure permitting rapid and accurate decisions on a governmental level. PMID- 26815992 TI - Protocol for Reports from Major Accidents and Disasters in the International Journal of Disaster Medicine. AB - The aim of this protocol is to achieve a prospective, standardized methodology for reporting results and experiences from major accidents and disasters so that the data can be used for analysis, to compare results, to exchange experiences and for international collaboration in methodological development. Using this form, the authors of the reports retain full credit for the data and the publication of them. At the same time, the data will be available in the journal and on the Internet (www.europeantrauma.net), thus providing the abovementioned possibilities for scientific analysis and development. PMID- 26815993 TI - Brachial Artery Injuries: A Seven-year Experience with a Prospective Database. AB - INTRODUCTION: A Trauma Vascular Registry was established in 1998. The aim of the study was to review brachial artery injuries. METHODS AND MATERIALS: Review of the prospective registry & case-notes of all identified Brachial Artery Injury. Data was captured on a proforma. RESULTS: 177 brachial artery injuries were identified, 154 (87%) were male, 130 were due to stab wounds (73,4%) while gunshots or other sharp trauma accounted for 27 injuries (16,1%). 17 blunt injuries and 3 other injuries were noted. The mid-brachial artery was injured most frequently (113; 68,3%). Angiograms were only performed in five patients and diagnosis was by clinical examination in the remaining patients. 22% of patients had a concomitant nerve injury, while 9 had humerus fractures. Repair was by vein graft in 92 patients (52%), while a primary repair was performed in 80 (45,2%). Specialist Registrars performed 142 repairs (80,3%). Sixteen patients (9%) required forearm fasciotomy, with four cases of limb loss. Three of the cases of limb loss presented over 6 hours post-injury. DISCUSSION AND CONCLUSIONS: Brachial artery injuries are the commonest vascular injuries to the limbs, with a good prognosis, provided early repair is undertaken. Arteriography is usually unnecessary and limb loss is low, provided appropriate decompression of a compartment syndrome is performed, however in this group the limb loss rate is 25% compared to the overall of 2%. The repair of a brachial artery is a good training procedure for surgical trainees, associated with a low morbidity. PMID- 26815994 TI - Physical and Psychosocial Factors Associated with Neck Pain after Major Accidental Trauma. AB - Neck pain after physical trauma is common; but previous research regarding the role of psychological and physical predictors for neck pain is inconsistent. A retrospective survey of consecutive patients presenting to a metropolitan trauma centre with major accidental trauma was performed between 1 and 6 years post injury. Possible predictor variables (demographic, injury severity, and psychosocial factors) were determined from the hospital trauma registry and the questionnaire. The main outcome was a combined score of neck pain severity and functional limitation. Multivariate logistic regression was performed to develop a predictive model for neck pain. A multivariate analysis of 355 patients showed that neck pain was not significantly associated with measures of injury severity. Neck pain was significantly more likely to be severe in patients with a cervical spine fracture, with pre-existing chronic illnesses, those with post-traumatic stress disorder (PTSD) at the time of follow up, those who had retained the services of a lawyer regarding the injury, and those with lower education levels. Psychosocial factors are important predictors of neck pain after major physical trauma. These findings do not support models for post-traumatic neck pain that are restricted to physical factors. PMID- 26815995 TI - Lateral Radiograph of the Hip in Fracture Neck of Femur: Is it a Ritual? AB - INTRODUCTION: Historically routine work up of a patient with a fracture neck of femur has always included an antero-posterior (AP) and a lateral view of the hip. The aim of the study was to know whether a lateral view of hip influenced the decision of an Orthopedic Surgeon regarding management at a District General Hospital. METHODS: A prospective study was conducted from February 2005 to September 2005 at Tameside General Hospital. X-rays of patients admitted with fracture neck of femur were shown to two independent observers in the daily trauma meeting. AP view of the hip was shown initially to observers and their classification and intended treatment was recorded. They were asked if they needed a lateral view to decide on management option and answers were recorded. The observers were then showed a lateral view of same hip and asked to comment on quality of film and also whether it would change their classification or intended management. RESULTS: There were 100 patients over six months. On AP view 56 were classified to have extra-capsular fracture, 37 were classified as displaced subcapital fracture and seven were classified undisplaced subcapital fracture. There was an interobserver variation in one patient between undisplaced or displaced subcapital fracture. The observers felt they would need a lateral X-ray on three occasions and there was a change in classification from undisplaced subcapital to displaced subcapital fracture on first occasion. There was no change in management plan in all the 100 patients after looking at a lateral X ray. CONCLUSION: We can conclude that unless required for management a lateral X ray of hip should be avoided routinely in all patients with fracture neck of femur as it would not only be cost effective but will also reduce radiation exposure to patient and relieve work pressure on radiographers, nursing and portering staff. PMID- 26815996 TI - Vacuum-Assisted Closure for Successful Treatment of a Major Contaminated Gunshot Chest-Wound: A Case Report. AB - Vacuum-assisted closure (VAC) is a well-established treatment for complicated wound infections and chronic wounds, including poststernotomy mediastinitis. The use of VAC in treating high-energy trauma has been more limited. We present a case where VAC was successfully used to treat a contaminated self-inflicted gunshot-wound of the chest and abdomen. PMID- 26815997 TI - Thoracic Outlet Syndrome Caused by a Pseudoaneurysm After Pseudarthrosis of the Clavicle. AB - Clavicle fractures are common, with the majority treated conservatively. If treated conservatively, pseudarthrosis of the clavicle is reported in up to 3% of the cases. In rare cases, pseudarthrosis of the clavicle may cause pseudoaneurysm formation, resulting in compression of the brachial plexus and the adjoining vessels, which may produce neurological symptoms and circulatory disorders. Here, we describe two cases of the late onset of pseudoaneurysm formation after pseudarthrosis of the clavicle. Both cases were remarkable because they showed clinical symptoms of TOS. Therefore, surgical treatment was performed and included claviculectomy, resection of the pseudoaneurysm and interposition grafting with an artificial prosthesis. One year after the operation, both patients showed excellent upper extremity function without any deficit of vascular, sensorial or motorial function. Patient's history and radiological findings are the keys to diagnosis. Without treatment, the prognosis is poor with spontaneous development of bleeding or gangrene. Therefore, surgical treatment has to be performed, especially when neurological symptoms occur. PMID- 26815998 TI - Unstable Cervical Spinal Injury in Children - Case Report and Review of the Literature. AB - Large studies about the management of pediatric patients with unstable flexion distraction injuries of the midcervical spine are rare. We present the case of a 12-year-old girl who sustained a cervical spinal injury with unilateral facet dislocation and discuss details and problems of diagnostic procedures and treatment in the light of the recent literature. The management and pitfalls of a unilateral facet dislocation in a child are summarized. After initial reposition, a multisegmental instability with neurology developed. Although distraction flexion cervical spine injuries are common in adults and often occur with concomitant neurological sequelae, they also can occur in the pediatric population. In conclusion, an MRI seems advisable. A treatment of postoperative malalignment with reposition via a halo-fixator cannot be recommended. Repositioning is possible but was lost when the fixator was removed. Comparing the historic and recent literature there is only weak evidence overall, nevertheless a ventral fusion seems to be the treatment option of choice. PMID- 26816000 TI - It may be harder than we thought, but political diversity will (still) improve social psychological science. AB - In our target article, we made four claims: (1) Social psychology is now politically homogeneous; (2) this homogeneity sometimes harms the science; (3) increasing political diversity would reduce this damage; and (4) some portion of the homogeneity is due to a hostile climate and outright discrimination against non-liberals. In this response, we review these claims in light of the arguments made by a diverse group of commentators. We were surprised to find near-universal agreement with our first two claims, and we note that few challenged our fourth claim. Most of the disagreements came in response to our claim that increasing political diversity would be beneficial. We agree with our critics that increasing political diversity may be harder than we had thought, but we explain why we still believe that it is possible and desirable to do so. We conclude with a revised list of 12 recommendations for improving political diversity in social psychology, as well as in other areas of the academy. PMID- 26815999 TI - A20 Deficiency in Lung Epithelial Cells Protects against Influenza A Virus Infection. AB - A20 negatively regulates multiple inflammatory signalling pathways. We here addressed the role of A20 in club cells (also known as Clara cells) of the bronchial epithelium in their response to influenza A virus infection. Club cells provide a niche for influenza virus replication, but little is known about the functions of these cells in antiviral immunity. Using airway epithelial cell specific A20 knockout (A20AEC-KO) mice, we show that A20 in club cells critically controls innate immune responses upon TNF or double stranded RNA stimulation. Surprisingly, A20AEC-KO mice are better protected against influenza A virus challenge than their wild type littermates. This phenotype is not due to decreased viral replication. Instead host innate and adaptive immune responses and lung damage are reduced in A20AEC-KO mice. These attenuated responses correlate with a dampened cytotoxic T cell (CTL) response at later stages during infection, indicating that A20AEC-KO mice are better equipped to tolerate Influenza A virus infection. Expression of the chemokine CCL2 (also named MCP-1) is particularly suppressed in the lungs of A20AEC-KO mice during later stages of infection. When A20AEC-KO mice were treated with recombinant CCL2 the protective effect was abrogated demonstrating the crucial contribution of this chemokine to the protection of A20AEC-KO mice to Influenza A virus infection. Taken together, we propose a mechanism of action by which A20 expression in club cells controls inflammation and antiviral CTL responses in response to influenza virus infection. PMID- 26816001 TI - Lack of anti-tumor activity by anti-VEGF treatments in hepatic hemangiomas. AB - Recently, anti-vascular endothelial growth factor (anti-VEGF) agents have been described in the literature as a valid treatment option for symptomatic liver hemangiomas, but only limited evidence supports this notion. The purpose of this study was to elucidate whether or not the administration of anti-VEGF agents can reliably achieve a size reduction in liver hemangiomas. We examined patients with incidental hemangiomas who received anti-angiogenic agents for the treatment of other malignancies. Our study population consisted of 17 colorectal cancer patients and one lung cancer patient carrying 21 hemangiomas who received bevacizumab, and seven renal cell carcinoma patients carrying nine hepatic hemangiomas who received sunitinib. We have measured the liver hemangioma volume on both the pre-treatment and post-treatment computed tomography images and then calculated the volume alteration rates. No statistically significant difference (P = 0.365) in the volume of the liver hemangiomas was observed before (1.1-168.8 cm(3); mean +/- SD 19.8 +/- 39.7 cm(3)) or after (1.2-163.6 cm(3); 19.3 +/- 38.0 cm(3)) bevacizumab treatment. The volume reduction rate ranged from -35.0 to 11.2 % (mean +/- SD -1.3 +/- 10.8 %). The sunitinib treatment group also showed no statistically significant difference (P = 0.889) in hemangioma volume before (1.2 6.5 cm(3); 3.0 +/- 1.8 cm(3)) or after (1.2-6.0 cm(3); 3.0-1.7 cm(3)) treatment. The volume reduction rate ranged from -13.3 to 7.7 % (median: mean +/- SD -2.5 +/ 6.6 %). We did not observe liver hemangioma shrinkage after bevacizumab or sunitinib treatment. Our data do not support the application of anti-VEGF agents for the treatment of hepatic hemangiomas. PMID- 26816002 TI - Frequency of Axial Spondyloarthritis Diagnosis Among Patients Seen by US Rheumatologists for Evaluation of Chronic Back Pain. AB - OBJECTIVE: To determine the proportion of patients with axial spondyloarthritis (SpA) among those with chronic back pain and >=1 of 3 SpA features in the US. METHODS: The study was conducted at rheumatology practices in the US. Patients were required to have chronic back pain for >=3 months beginning at <45 years of age, no prior SpA diagnosis, and >=1 of the following 3 SpA features: HLA-B27 positivity, current inflammatory back pain, and magnetic resonance imaging (MRI) or radiographic evidence of sacroiliitis. Medical history and physical examination findings, pelvic radiographs, MRIs of sacroiliac joints, C-reactive protein (CRP) level, and HLA-B27 status were obtained. Investigators were asked if a clinical diagnosis of axial SpA could be made based on the results. Data were also analyzed separately to determine if patients fulfilled the Assessment of SpondyloArthritis international Society (ASAS) criteria for axial SpA and/or modified New York criteria for ankylosing spondylitis (AS). RESULTS: A total of 751 patients were enrolled (46% were existing patients in rheumatology practices, 40% were new referrals, and 14% were self referred). Among patients with available data, 319 of 697 (46%) were diagnosed as having axial SpA by the investigator, and 348 of 744 (47%) fulfilled the ASAS criteria, of whom 238 were classified as having nonradiographic axial SpA and 108 as having AS; 2 had missing data. Using investigator's clinical diagnosis as the gold standard, the specificity and sensitivity of the ASAS criteria were 79% and 81%, respectively. CONCLUSION: Our findings indicate that among patients with chronic back pain for >=3 months beginning at ages younger than 45 years, the presence of >=1 of 3 SpA features is an effective way to identify those with possible axial SpA. PMID- 26816003 TI - Perioperative angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers for preventing mortality and morbidity in adults. AB - BACKGROUND: Perioperative hypertension requires careful management. Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) have shown efficacy in treating hypertension associated with surgery. However, there is lack of consensus about whether they can prevent mortality and morbidity. OBJECTIVES: To systematically assess the benefits and harms of administration of ACEIs or ARBs perioperatively for the prevention of mortality and morbidity in adults (aged 18 years and above) undergoing any type of surgery under general anaesthesia. SEARCH METHODS: We searched the current issue of the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 12), Ovid MEDLINE (1966 to 8 December 2014), EMBASE (1980 to 8 December 2014), and references of the retrieved randomized trials, meta-analyses, and systematic reviews. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing perioperative administration of ACEIs or ARBs with placebo in adults (aged 18 years and above) undergoing any type of surgery under general anaesthesia. We excluded studies in which participants underwent procedures that required local anaesthesia only, or participants who had already been on ACEIs or ARBs. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, assessed the risk of bias, and extracted data. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included seven RCTs with a total of 571 participants in the review. Two of the seven trials involved 36 participants undergoing non-cardiac vascular surgery (infrarenal aortic surgery), and five involved 535 participants undergoing cardiac surgery, including valvular surgery, coronary artery bypass surgery, and cardiopulmonary bypass surgery. The intervention was started from 11 days to 25 minutes before surgery in six trials and during surgery in one trial. We considered all seven RCTs to carry a high risk of bias. The effects of ACEIs or ARBs on perioperative mortality and acute myocardial infarction were uncertain because the quality of the evidence was very low. The risk of death was 2.7% in the ACEIs or ARBs group and 1.6% in the placebo group (risk ratio (RR) 1.61; 95% confidence interval (CI) 0.44 to 5.85). The risk of acute myocardial infarction was 1.7% in the ACEIs or ARBs group and 3.0% in the placebo group (RR 0.55; 95% CI 0.14 to 2.26). ACEIs or ARBs may improve congestive heart failure (cardiac index) perioperatively (mean difference (MD) -0.60; 95% CI -0.70 to -0.50, very low-quality evidence). In terms of rate of complications, there was no difference in perioperative cerebrovascular complications (RR 0.48; 95% CI 0.18 to 1.28, very low-quality evidence) and hypotension (RR 1.95; 95% CI 0.86 to 4.41, very low-quality evidence). Cardiac surgery-related renal failure was not reported. ACEIs or ARBs were associated with shortened length of hospital stay (MD -0.54; 95% CI -0.93 to -0.16, P value = 0.005, very low-quality evidence). These findings should be interpreted cautiously due to likely confounding by the clinical backgrounds of the participants. ACEIs or ARBs may shorten the length of hospital stay, (MD 0.54; 95% CI -0.93 to -0.16, very low-quality evidence) Two studies reported adverse events, and there was no evidence of a difference between the ACEIs or ARBs and control groups. AUTHORS' CONCLUSIONS: Overall, this review did not find evidence to support that perioperative ACEIs or ARBs can prevent mortality, morbidity, and complications (hypotension, perioperative cerebrovascular complications, and cardiac surgery-related renal failure). We found no evidence showing that the use of these drugs may reduce the rate of acute myocardial infarction. However, ACEIs or ARBs may increase cardiac output perioperatively. Due to the low and very low methodology quality, high risk of bias, and lack of power of the included studies, the true effect may be substantially different from the observed estimates. Perioperative (mainly elective cardiac surgery, according to included studies) initiation of ACEIs or ARBs therapy should be individualized. PMID- 26816004 TI - New-onset cutaneous lichen planus following therapy for hepatitis C with ledipasvir-sofosbuvir. PMID- 26816006 TI - Peroxidase to Cytochrome b Type Transition in the Active Site of Heme-Bound Amyloid beta Peptides Relevant to Alzheimer's Disease. AB - Recent evidence has established the colocalization of amyloid-rich plaques and heme-rich deposits in the human cerebral cortex as a common postmortem feature in Alzheimer's disease (AD). The amyloid beta (Abeta) peptides have been shown to bind heme, and the resultant heme-Abeta complexes can generate toxic partially reduced oxygen species (PROS) and exhibit peroxidase activity. The heme-Abeta active site exhibits a concentration-dependent equilibrium between a high-spin mono-His-bound species similar to a peroxidase-type active site and a bis-His bound six-coordinate low-spin species similar to that of a cytochrome b type active site. The nu(Fe-His) (241 cm(-1)) vibration has been identified in the high-spin heme-Abeta active site by resonance Raman spectroscopy. The formation of the low-spin heme-Abeta species is promoted by the His14 and noncoordinating second-sphere Arg5 residues. The high-spin state produces more PROS than the low spin species. Nonbiological constructs modeling different forms of Abeta (oligomers, fibrils, etc.) suggest that the detrimental high-spin state is likely to dominate under most physiological conditions. PMID- 26816007 TI - Opioid Prescribing for Chronic Pain--Achieving the Right Balance through Education. PMID- 26816005 TI - Homologous Transcription Factors DUX4 and DUX4c Associate with Cytoplasmic Proteins during Muscle Differentiation. AB - Hundreds of double homeobox (DUX) genes map within 3.3-kb repeated elements dispersed in the human genome and encode DNA-binding proteins. Among these, we identified DUX4, a potent transcription factor that causes facioscapulohumeral muscular dystrophy (FSHD). In the present study, we performed yeast two-hybrid screens and protein co-purifications with HaloTag-DUX fusions or GST-DUX4 pull down to identify protein partners of DUX4, DUX4c (which is identical to DUX4 except for the end of the carboxyl terminal domain) and DUX1 (which is limited to the double homeodomain). Unexpectedly, we identified and validated (by co immunoprecipitation, GST pull-down, co-immunofluorescence and in situ Proximal Ligation Assay) the interaction of DUX4, DUX4c and DUX1 with type III intermediate filament protein desmin in the cytoplasm and at the nuclear periphery. Desmin filaments link adjacent sarcomere at the Z-discs, connect them to sarcolemma proteins and interact with mitochondria. These intermediate filament also contact the nuclear lamina and contribute to positioning of the nuclei. Another Z-disc protein, LMCD1 that contains a LIM domain was also validated as a DUX4 partner. The functionality of DUX4 or DUX4c interactions with cytoplasmic proteins is underscored by the cytoplasmic detection of DUX4/DUX4c upon myoblast fusion. In addition, we identified and validated (by co immunoprecipitation, co-immunofluorescence and in situ Proximal Ligation Assay) as DUX4/4c partners several RNA-binding proteins such as C1QBP, SRSF9, RBM3, FUS/TLS and SFPQ that are involved in mRNA splicing and translation. FUS and SFPQ are nuclear proteins, however their cytoplasmic translocation was reported in neuronal cells where they associated with ribonucleoparticles (RNPs). Several other validated or identified DUX4/DUX4c partners are also contained in mRNP granules, and the co-localizations with cytoplasmic DAPI-positive spots is in keeping with such an association. Large muscle RNPs were recently shown to exit the nucleus via a novel mechanism of nuclear envelope budding. Following DUX4 or DUX4c overexpression in muscle cell cultures, we observed their association with similar nuclear buds. In conclusion, our study demonstrated unexpected interactions of DUX4/4c with cytoplasmic proteins playing major roles during muscle differentiation. Further investigations are on-going to evaluate whether these interactions play roles during muscle regeneration as previously suggested for DUX4c. PMID- 26816008 TI - The Residency Application Process--Burden and Consequences. PMID- 26816009 TI - Do-It-Yourself Medical Devices--Technology and Empowerment in American Health Care. PMID- 26816010 TI - The Spaces Between. PMID- 26816011 TI - Belatacept and Long-Term Outcomes in Kidney Transplantation. AB - BACKGROUND: In previous analyses of BENEFIT, a phase 3 study, belatacept-based immunosuppression, as compared with cyclosporine-based immunosuppression, was associated with similar patient and graft survival and significantly improved renal function in kidney-transplant recipients. Here we present the final results from this study. METHODS: We randomly assigned kidney-transplant recipients to a more-intensive belatacept regimen, a less-intensive belatacept regimen, or a cyclosporine regimen. Efficacy and safety outcomes for all patients who underwent randomization and transplantation were analyzed at year 7 (month 84). RESULTS: A total of 666 participants were randomly assigned to a study group and underwent transplantation. Of the 660 patients who were treated, 153 of the 219 patients treated with the more-intensive belatacept regimen, 163 of the 226 treated with the less-intensive belatacept regimen, and 131 of the 215 treated with the cyclosporine regimen were followed for the full 84-month period; all available data were used in the analysis. A 43% reduction in the risk of death or graft loss was observed for both the more-intensive and the less-intensive belatacept regimens as compared with the cyclosporine regimen (hazard ratio with the more intensive regimen, 0.57; 95% confidence interval [CI], 0.35 to 0.95; P=0.02; hazard ratio with the less-intensive regimen, 0.57; 95% CI, 0.35 to 0.94; P=0.02), with equal contributions from the lower rates of death and graft loss. The mean estimated glomerular filtration rate (eGFR) increased over the 7-year period with both belatacept regimens but declined with the cyclosporine regimen. The cumulative frequencies of serious adverse events at month 84 were similar across treatment groups. CONCLUSIONS: Seven years after transplantation, patient and graft survival and the mean eGFR were significantly higher with belatacept (both the more-intensive regimen and the less-intensive regimen) than with cyclosporine. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00256750.). PMID- 26816012 TI - Prevalence and Characteristics of Physicians Prone to Malpractice Claims. AB - BACKGROUND: The distribution of malpractice claims among physicians is not well understood. If claim-prone physicians account for a substantial share of all claims, the ability to reliably identify them at an early stage could guide efforts to improve care. METHODS: Using data from the National Practitioner Data Bank, we analyzed 66,426 claims paid against 54,099 physicians from 2005 through 2014. We calculated concentrations of claims among physicians. We used multivariable recurrent-event survival analysis to identify characteristics of physicians at high risk for recurrent claims and to quantify risk levels over time. RESULTS: Approximately 1% of all physicians accounted for 32% of paid claims. Among physicians with paid claims, 84% incurred only one during the study period (accounting for 68% of all paid claims), 16% had at least two paid claims (accounting for 32% of the claims), and 4% had at least three paid claims (accounting for 12% of the claims). In adjusted analyses, the risk of recurrence increased with the number of previous paid claims. For example, as compared with physicians who had one previous paid claim, the 2160 physicians who had three paid claims had three times the risk of incurring another (hazard ratio, 3.11; 95% confidence interval [CI], 2.84 to 3.41); this corresponded in absolute terms to a 24% chance (95% CI, 22 to 26) of another paid claim within 2 years. Risks of recurrence also varied widely according to specialty--for example, the risk among neurosurgeons was four times as great as the risk among psychiatrists. CONCLUSIONS: Over a recent 10-year period, a small number of physicians with distinctive characteristics accounted for a disproportionately large number of paid malpractice claims. PMID- 26816014 TI - IMAGES IN CLINICAL MEDICINE. Primary and Secondary Syphilis. PMID- 26816013 TI - Neurobiologic Advances from the Brain Disease Model of Addiction. PMID- 26816015 TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 3-2016. A 9-Year-Old Girl with Intermittent Abdominal Pain. PMID- 26816017 TI - The Clearer BENEFITS of Belatacept. PMID- 26816016 TI - Progress in Chronic Lymphocytic Leukemia with Targeted Therapy. PMID- 26816018 TI - CLINICAL DECISIONS. Ductal Carcinoma In Situ. PMID- 26816019 TI - Antiretroviral Therapy in Early HIV Infection. PMID- 26816020 TI - Antiretroviral Therapy in Early HIV Infection. PMID- 26816021 TI - Antiretroviral Therapy in Early HIV Infection. PMID- 26816022 TI - Randomized Trial of Reduced-Nicotine Standards for Cigarettes. PMID- 26816023 TI - Randomized Trial of Reduced-Nicotine Standards for Cigarettes. PMID- 26816024 TI - Randomized Trial of Reduced-Nicotine Standards for Cigarettes. PMID- 26816025 TI - Randomized Trial of Reduced-Nicotine Standards for Cigarettes. PMID- 26816026 TI - 10-Year Survival of Patients with AIDS Receiving Antiretroviral Therapy in Haiti. PMID- 26816027 TI - IMAGES IN CLINICAL MEDICINE. Cannon A Waves. PMID- 26816028 TI - Erratum to: Cost Effectiveness of Tiotropium in Patients with Asthma Poorly Controlled on Inhaled Glucocorticosteroids and Long-Acting beta-Agonists. PMID- 26816029 TI - Human Visual System as a Double-Slit Single Photon Interference Sensor: A Comparison between Modellistic and Biophysical Tests. AB - This paper describes a computational approach to the theoretical problems involved in the Young's single-photon double-slit experiment, focusing on a simulation of this experiment in the absence of measuring devices. Specifically, the human visual system is used in place of a photomultiplier or similar apparatus. Beginning with the assumption that the human eye perceives light in the presence of very few photons, we measure human eye performance as a sensor in a double-slit one-photon-at-a-time experimental setup. To interpret the results, we implement a simulation algorithm and compare its results with those of human subjects under identical experimental conditions. In order to evaluate the perceptive parameters exactly, which vary depending on the light conditions and on the subject's sensitivity, we first review the existing literature on the biophysics of the human eye in the presence of a dim light source, and then use the known values of the experimental variables to set the parameters of the computational simulation. The results of the simulation and their comparison with the experiment involving human subjects are reported and discussed. It is found that, while the computer simulation indicates that the human eye has the capacity to detect the corpuscular nature of photons under these conditions, this was not observed in practice. The possible reasons for the difference between theoretical prediction and experimental results are discussed. PMID- 26816030 TI - Emergency Department-based Opioid Harm Reduction: Moving Physicians From Willing to Doing. AB - OBJECTIVES: Develop and internally validate a survey tool to assess emergency department (ED) physician attitudes, clinical practice, and willingness to perform opiate harm reduction (OHR) interventions and to identify barriers and facilitators in translating willingness to action. METHODS: This study was an anonymous, Web-based survey based on the Theory of Planned Behavior of ED physicians at three tertiary referral centers. Construction and internal validation of scaled questions was assessed through principal component and Cronbach's alpha analyses. Stepwise linear regression was conducted to measure impact of physician knowledge, attitudes, confidence, and self-efficacy on willingness to perform OHR interventions including opioid overdose education; naloxone prescribing; and referral to naloxone, methadone, and syringe access programs. RESULTS: A total of 200 of 278 (71.9%) physicians completed the survey. Principal component analysis yielded five components: attitude, confidence, self efficacy, professional impact factors, and personal impact factors. Overall, respondents were willing to perform OHR interventions, but few actually do. Willingness was correlated with attitude, confidence, and self-efficacy (R(2) = 0.50); however, overall physicians lacked confidence (mean = 3.06 of 5, 95% confidence interval [CI] = 2.94 to 3.18]). Knowledge, time, training, and institutional support were all prohibitive barriers. Physicians reported that research evidence, professional organization recommendations, and opinions of ED leaders would strongly influence a change in their clinical practice to incorporate OHR interventions (mean = 4.25 of 5, 95% CI = 4.18 to 4.32). CONCLUSIONS: Compared to prior studies, emergency medicine physicians had increased willingness to perform OHR interventions, but there remains a disparity between willingness and clinical practice. Influential factors that may move physicians from "willing" to "doing" include dissemination of supportive research evidence; professional organization endorsement; ED leadership opinion; and addressing time, knowledge, and institutional barriers. PMID- 26816032 TI - Pediatric Polytrauma: Always a Strong Challenge. PMID- 26816031 TI - Intake of fish and long-chain omega-3 polyunsaturated fatty acids and incidence of metabolic syndrome among American young adults: a 25-year follow-up study. AB - PURPOSE: Studies suggest that long-chain omega-3 polyunsaturated fatty acid (LComega3PUFA) intake and its primary food source-fish-may have beneficial effects on the individual components of metabolic syndrome (MetS). We examined the longitudinal association between fish or LComega3PUFA intake and MetS incidence. METHODS: We prospectively followed 4356 American young adults, free from MetS and diabetes at baseline, for incident MetS and its components in relation to fish and LComega3PUFA intake. MetS was defined by the National Cholesterol Education Program/Adult Treatment Panel III criteria. Cox proportional hazards model was used for analyses, controlling for socio demographic, behavioral, and dietary factors. RESULTS: During the 25-year follow up, a total of 1069 incident cases of MetS were identified. LComega3PUFA intake was inversely associated with the incidence of MetS in a dose-response manner. The multivariable adjusted hazards ratio (HR) [95 % confidence interval (CI)] of incident MetS was 0.54 (95 % CI 0.44, 0.67; P for linear trend < 0.01) as compared the highest to the lowest quintile of LComega3PUFA intake. A threshold inverse association was found between non-fried fish consumption and the incidence of MetS. The multivariable adjusted HRs (95 % CIs) from the lowest to the highest quintile were 1.00, 0.70 (0.51, 0.95), 0.68 (0.52, 0.91), 0.67 (0.53, 0.86), and 0.71 (0.56, 0.89) (P for linear trend = 0.49). The observed inverse associations were independent of the status of baseline individual components of MetS. CONCLUSIONS: Our findings suggest that intakes of LComega3PUFAs and non fried fish in young adulthood are inversely associated with the incidence of MetS later in life. PMID- 26816033 TI - European Journal of Trauma and Emergency Surgery Receives an Impact Factor. PMID- 26816034 TI - Prehospital and Early Clinical Care of Infants, Children, and Teenagers Compared to an Adult Cohort : Analysis of 2,961 Children in Comparison to 21,435 Adult Patients from the Trauma Registry of DGU in a 15-Year Period. AB - BACKGROUND: Although the incidence of pediatric patients in emergency services is as low as 5-10%, trauma remains one of the leading causes of death during childhood. Only a few reports exist about the quality of the initial treatment of pediatric trauma patients. Therefore, we tested the hypothesis of whether prehospital treatment and emergency management in pediatric trauma patients is similar to the treatment that is provided for adult patients. MATERIALS AND METHODS: We performed a retrospective data analysis of the German Trauma Registry of the DGU from January 1993 to December 2007. Exclusion criteria were missing information about injury severity and/or age and patients older than 50 years. All pediatric patients were subdivided into five groups (infants 0-1 year, toddlers 2-5 years, children 6-9 years, pupils 10-13 years, teenagers 14-17 years) with regard to their age and were compared with the adult cohort (18-50 years). From 24,396 patients, 2,961 were below 18 years of age, thus, about 12% of the whole population of injured patients below the age of 50 years. RESULTS: 66.4% of infants sustained relevant head injuries (Abbreviated Injury Scale [AIS] >=3), and this rate declined with increasing age. The mean Injury Severity Score (ISS) increased from 21.0 (+/-11.6) in the group of infants to 26.7 (+/-13.9) in the adult cohort. In all groups, the majority of patients were male. The injury pattern differed according to age, with predominant traumatic brain injury (TBI) in infants. During the preclinical treatment, infants were less often intubated and this was contrasted by a higher rate of cardiopulmonary resuscitation in this group (infants 16.2%, toddlers 6.8%, adults 3.1%). Diagnostic multislice computed tomography (CT) examination was less often performed in infants as compared to the other groups (infants 57.1%, toddlers 77.2%, adults 77.8%). Mortality and quality indicators such as timelines show no significant differences between children and adults. CONCLUSION: We observed typical age-dependent differences regarding the injury pattern and severity and differences referring to the preclinical and initial treatment. With respect to the high rate of serious TBI in the infants and toddlers age groups, a more focused education and training of emergency physicians and paramedics should be considered. PMID- 26816035 TI - Outcomes in Pediatric Trauma Care in the Stockholm Region. AB - BACKGROUND: Although trauma is a leading cause of pediatric mortality and morbidity in Sweden, few studies have examined the outcome of pediatric trauma. OBJECTIVE: Here, we describe the age and gender distribution, injury mechanisms, injury severity, and outcome of pediatric trauma in the Stockholm region. METHODS: This retrospective study comprises all trauma patients (age <= 15 years) admitted to a regional pediatric trauma center and all pediatric deaths due to trauma in Stockholm in 2002. Data from the trauma registry database were verified by comparison with medical records and autopsy reports. Outcome was measured by mortality and length of stay in a pediatric intensive care unit (PICU) and acute care hospital. RESULTS: In all, 432 injured children were included. The median age was 10 years and 59% were males. The median injury severity score was 4 (interquartile range [IQR] 1-9) and 50% sustained head injuries. Mortality was low (1%) and the median length of hospital stay was 2 days (IQR 1-3); 19% stayed in a PICU and, of those, 89% stayed for one day. Comparison with medical records showed that much information in the trauma registry database was either incorrect or missing. CONCLUSIONS: Many injuries were minor and half of the children were discharged home from the emergency department.Head injurieswere themost common injury in all age groups. The most severe head injuries were seen in the youngest group and were caused by falls. Trauma team activation criteria should be improved to avoid overutilization. The quality and completeness of data in the trauma registry must be enhanced. PMID- 26816036 TI - Role of Neuroprotein S-100B in the Diagnostic of Pediatric Mild Brain Injury. AB - Traumatic brain injury is one of the leading causes of death and disability in children and adolescents. Patients with moderate or severe lesions can be readily recognized clinically, require immediate radiologic diagnostics by computed tomography (CT) or magnetic resonance imaging (MRI), admission to intensive care units, and, in some cases, will go on to require neurosurgical intervention. Patients with mild traumatic brain injuries (MTBIs) are diagnostically challenging. Often, the event is unobserved and head injury can only be suspected. Clinical symptoms are unreliable and clinical findings from neurological examination have to be interpreted with care. As a small percentage of MTBI patients progress to have a life-threatening intracranial hemorrhage, the recognition of this group of patients and their judicious and timely management is, therefore, an important goal. Subjecting every MTBI patient to a cranial CT scanning results in high costs and unnecessary exposure to ionizing radiation. Admitting all MTBI patients for observation and performing CTs only in case of clinical deterioration is costly and a substantial drain on resources, not to mention the radiation exposure and a source of stress for the majority of patients. Current European guidelines for diagnostics and therapy in MTBI patients are only partially applicable to the pediatric population. This article reviews the clinical problem, treatment options and guidelines, as well as diagnostic tools, with special focus on neuroprotein S-100B in pediatric and adolescent patients with MTBIs. PMID- 26816038 TI - Epidemiology and Management of Injuries to the Spinal Cord and Column in Pediatric Multiple-Trauma Patients. AB - Injuries to the spinal column and cord in children are a rare condition. Epidemiological data could help to establish an evidence-based assessment and therapy of these patients. We present a retrospective chart analysis of children with spinal injuries who were admitted to the emergency room. The patients were analyzed regarding age, mechanism, and distribution of their injuries to all spinal regions and treatment strategies. Thirty-five children met the inclusion criteria with severe spinal injuries (Abbreviated Injury Scale [AIS] for Region 6 [spine]; AIS region 6) in a period from January 2003 to December 2009. The incidence was extremely low in younger children, with increasing numbers during adolescence. Neurological deficit without fracture accounted for almost 25% of all patients. The majority of patients were treated conservatively; operative treatment was performed in 25% of patients with unstable fractures, particularly in adolescents. Treatment strategies differ according to the type and degree of injury, age, and level of spine maturation. PMID- 26816037 TI - Pediatric Polytrauma Management. AB - Caring for pediatric trauma patients requires an understanding of the distinct anatomy and pathophysiology of the pediatric population compared to adult trauma patients. Initial evaluation, management, and resuscitation are performed as a multidisciplinary approach including pediatric physicians, trauma surgeons, and pediatric intensive care physicians. Head injury severity is the principle determinant of outcome and mortality in polytraumatized children. Abdominal injuries rarely require surgery in contrast to adults, but need to be detected. Spine and pelvic injuries as well as injuries of the extremities require age adapted surgical procedures. However, the degree of recovery in polytraumatized children is often remarkable, even after apparently devastating injuries. Maximal care should, therefore, be rendered under the assumption that a complete recovery will be made. PMID- 26816039 TI - A Portable CT Scanner in the Pediatric Intensive Care Unit Decreases Transfer Associated Adverse Events and Staff Disruption. AB - INTRODUCTION: Computerized tomography (CT) is an important diagnostic tool in the management of critically ill children, especially those with neurosurgical problems such as traumatic brain injury. Traditionally, such scans require transfer to the radiology department (RD) at times of extreme physiological instability, such as incipient cerebral herniation, and exposes children with actual, or potential, spinal injuries to the risks of transfer. Moving children from pediatric intensive care (PIC), often overnight, also depletes units of senior staff. Portable CT (PCT) scanning offers a solution to this problem, and we assessed patient stability and staff time occupied during urgent CT scans before and after the introduction of a PCT scanner (CereTom((r))) in a regional neurosurgical pediatric intensive care unit (PICU). MATERIALS AND METHODS: Prospective observational study of ventilated children in the PICU requiring urgent CT of the head to limit secondary brain injury. Data was collected for three months prior to, and for the same period after, the introduction of PCT on a questionnaire designed to assess physiological variables, PICU interventions, and staff time, which was completed immediately post scanning. RESULTS: Eight children had urgent CT head scan in the RD during the first 3 months and ten PCT in the second 6 months. The patients transferred to the RD required medical intervention because of cardio-respiratory instability or fluctuating intracranial pressure in nearly every patient and clearly increased the strain on staff resources. None of those patients undergoing PCT had untoward events and staff resources were far less impacted upon. DISCUSSION: PCT scanning is safe for unstable neurosurgical patients who need urgent diagnostic head CT, reducing the risks associated with transfer and the depletion of staff provision to the other children in the PICU. While this study did not specifically address image quality, all images were diagnostic regarding the indication for scanning. PMID- 26816040 TI - Immobilization Regime Following Lateral Patellar Dislocation: A Systematic Review and Meta-Analysis of the Current Evidence Base. AB - Historically, patients following patellar dislocation have been immobilized in a cylinder plaster of Paris cast for around 6 weeks. However, there remains controversy over whether immobilization should be advocated following this injury. There also remains debate over the methods and duration for which patients are immobilized. A systematic review was undertaken to assess these questions. The electronic databases MEDLINE, EMBASE, CINAHL, and AMED, in addition to a review of unpublished material, was undertaken. All of the included papers were appraised using the CASP appraisal tool. Two studies were eligible, assessing the outcomes of 177 lateral patellar dislocations. The results suggested that there is no significant difference in clinical outcomes when using a cylinder cast or posterior splint in full extension compared to an elastic bandage. No studies were identified specifically assessing the clinical outcomes of patients immobilized compared to those not immobilized, or assessing different durations of immobilization. The present evidence base is insufficient in both size and methodological quality to justify the use of immobilization for patients following a lateral patellar dislocation. PMID- 26816041 TI - Disproportionate Acidosis After Traumatic Bladder Rupture: A Case-Control Study. AB - BACKGROUND: Traumatic bladder injury is rare and often missed on initial evaluation. We sought to identify early markers of bladder injury with a high sensitivity. METHODS: A retrospective review from 1999 to 2008. RESULTS: There were 28 patients diagnosed with traumatic bladder injury. The most common mechanism was car accidents with pelvic fractures. 93% (26) of the patients presented with significant metabolic acidosis, without evidence of hemorrhagic shock. For intra- and extraperitioneal bladder ruptures, the mean hemoglobin level on arrival was 12.4 + 2.0 (range 9.0-16.0) and 11.4 + 1.9 (range 8.2-14.7). The average pH on arrival for intraperitoneal ruptures was 7.22 + 0.16 (range 6.86-7.37) and for extraperitoneal ruptures, 7.22 + 0.16 (range 6.85-7.37). The pH improved in all patients with intraperitoneal rupture after surgical repair, up to a mean of 7.27 + 0.11 (range 7.06-7.36, p = 0.5) within 12 h. Extraperitoneal ruptures recovered more quickly with a pH after catheter drainage of 7.34 + 0.04 (range 7.27-7.37, p = 0.1) within 12 h. The ISS for intraperitoneal and extraperitoneal ruptures were similar, 30 + 12 (range 13-57) and 32 + 13 (range 13-57, p = 0.7). A cohort of trauma patients, matched by ISS, age, and pelvic fracture, but without bladder rupture, was used for comparison. Their mean ISS was 30 + 10 (range 14-57). The average pH for this group on arrival was 7.33 + 0.11 (range 7.16-7.42), and 47% of these patients had a normal pH. There was a significant difference between the pH on arrival in the ruptured compared to the nonruptured cohort (intraperitoneal pH 7.22, p = 0.008, extraperitoneal pH 7.22, p = 0.02). Three patients died (mortality 10.7%). CONCLUSIONS: Disproportionate acidosis in the trauma patient is a sensitive indicator of bladder injury, especially with a pelvic fracture or hematuria. Fully resuscitated patients with persistent acidosis and an appropriate mechanism should be evaluated for bladder injury. PMID- 26816042 TI - The Kocher-Langenbeck Approach: Differences in Outcome of Transverse Acetabular Fractures Depending on the Patient's Position. AB - INTRODUCTION: The Kocher-Langenbeck approach is most frequently used for open reduction and internal fixation of transverse acetabular fractures, the positioning of the patient still falling to the preference of the surgeon. The impact of 'prone' and 'lateral' positioning on radiographic outcome and postoperative complication rates was evaluated by this retrospective study. METHODS: Between 2002 and 2007, 27 consecutive cases of transverse acetabular fractures were treated randomly by four attending surgeons at a Level I trauma center, 18 done in a lateral and nine in a prone position, with no significant difference in age and pre- and intraoperative parameters; no patients were excluded. The complication rate was analyzed by medical records. After an average of 9 months postoperatively, the radiographic outcome was evaluated by plain X rays and computed tomography (CT) scans using the Matta system, the Epstein classification, and the Brooker grades. Post-traumatic arthrosis and avascular necrosis of the femoral head were documented. RESULTS: We found a significantly poorer quality of fracture reduction (p = 0.032) and higher rate of posttraumatic arthrosis (p = 0.049) for patients who were operated for transverse acetabular fracture in the lateral versus the prone position. No revision surgery was needed; no infection was detected overall, whereas two iatrogenic nerve damages (one temporary, one persistent) were found only in the lateral group. There was no significant difference concerning extensive blood loss, femoral head necrosis, Epstein grades, heterotopic ossification, and secondary surgery needed. CONCLUSIONS: The weight of the leg may make reduction more difficult in the lateral position, leading to a poorer radiographic outcome. PMID- 26816043 TI - Ruptured Hydatid Cysts into the Peritoneum: A Case Series. AB - INTRODUCTION: The rupture of a hydatid cyst into the abdominal cavity is a rare and serious complication. METHODS: In this retrospective study, we evaluated ten patients who were surgically treated for ruptured hydatid cysts into the peritoneum at a university hospital in an endemic area between 2003 and 2008. RESULTS: There were three female and seven male patients, with a mean age of 34.2 years (range 20-79). Ruptured cysts were located in the liver (7), pelvis (2), and spleen (1). Eight patients had other nonperforated hydatid cysts. Perforations were spontaneous in seven patients and traumatic in three. Patients' diagnoses were done with abdominal ultrasound (3), computed tomography (6), and laparotomy (1). The surgical treatment of perforated cysts were radical (pericystectomy) in one patient and conservative (partial pericystectomy) in the other nine patients. There was postoperative morbidity (surgical site infection) in one patient and one postoperative recurrence of disease in another patient. Mortality was seen in one patient 2 months after operation due to pulmonary hydatid cyst and infection. CONCLUSION: The rupture of hydatid cysts into the peritoneal cavity should be included in the differential diagnosis of acute abdominal pain in endemic areas. Perforation in a young patient may be the first presentation of hydatid cyst. Multiple hydatid cysts may be a predisposing factor for perforation. Location of the cyst on segment VI of the liver may be a predisposing factor as well. Emergency surgery is the main treatment for intraperitoneal rupture of hydatid cysts and medical treatment should be given postoperatively. PMID- 26816044 TI - Management of Traumatic Coronary Artery Injuries: Advantages of Off-Pump Coronary Artery Bypass. AB - Coronary artery injuries are rare but highly lethal. Debate exists as to the best treatment for this complex set of injuries, with historical treatment favoring arterial ligation. Although conventional coronary artery bypass grafting using cardiopulmonary bypass has been used somewhat successfully, enthusiasm for off pump CABG (OPCAB) has grown more recently. We report two unique cases of left anterior descending coronary arterial injuries managed successfully with OPCAB. PMID- 26816045 TI - Rupture of Flexor Pollicis Longus Tendon: A Complication of Volar Locking Plating of the Distal Radius. AB - We report an unusual case of complete rupture of the flexor pollicis longus tendon following volar locking plating for a distal radius fracture. We believe that the prominence of a distal locking screw head predisposed to the rupture of the tendon. We highlight that correctly attaching the distal locking screws to the plate is essential for obtaining the correct biomechanics of the device and preventing flexor tendon rupture. PMID- 26816046 TI - Proximal Tibial Sleeve Fracture: Case Report of a Rare Injury and Review of the Literature. AB - A sleeve fracture occurs when a ''sleeve'' of cartilage or periosteum is avulsed with or without an osseous fragment, an injury most commonly reported in the patella. Proximal tibial sleeve fractures are extremely rare and we present a case in an adolescent male who had concomitant osteochondral as well as chondral fractures of his patella. Sleeve fractures present in the skeletally immature, and may look relatively benign on radiographs, but misdiagnosis may lead to adverse consequences. Clinicians should have a high index of suspicion if a child or adolescent presents with a knee injury with clinical concerns regarding the extensor mechanism. Given that the ''sleeve'' of the injury contains tissue with osteogenic potential, we recommend that displaced proximal tibial sleeve fractures should be managed operatively to avoid dysfunction of the extensor mechanism. These patients should also have perioperative assessment for occult osteochondral and chondral injuries that are potentially repairable and thus may have implications for prognosis. PMID- 26816047 TI - Triplane Fracture of the Distal Fibula. AB - This is a case report of a 14-year-old girl with a triplane fracture of the distal fibula. The fracture showed displacement and was treated by open reduction, internal fixation, and 5 weeks of external immobilization. The follow up 5 months after injury yielded an excellent clinical result. Triplane fractures are also seen in locations other than the growth plate of the distal tibia. Due to the occurrence close to the end of the growth period, the potential for growth deformity is negligible. There has been no previous report of a transitional fracture in this location. PMID- 26816048 TI - Mitral Valve Vegetation in Antiphospholipid Syndrome. PMID- 26816049 TI - Initial integration of chiropractic services into a provincially funded inner city community health centre: a program description. AB - BACKGROUND: The burden of fees for chiropractic services rendered often falls on the patient and must be provided out-of-pocket regardless of their socioeconomic status and clinical need. Universal healthcare coverage reduces the financial barrier to healthcare utilization, thereby increasing the opportunity for the financially disadvantaged to have access to care. In 2011 the Canadian Province of Manitoba initiated a pilot program providing access to chiropractic care within the Mount Carmel Clinic (MCC), a non-secular, non-profit, inner city community health centre. OBJECTIVE: To describe the initial integration of chiropractic services into a publically funded healthcare facility including patient demographics, referral patterns, treatment practices and clinical outcomes. METHOD: A retrospective database review of chiropractic consultations in 2011 (N=177) was performed. RESULTS: The typical patient referred for chiropractic care was a non-working (86%), 47.3(SD=16.8) year old, who self identified as Caucasian (52.2%), or Aboriginal (35.8%) and female (68.3%) with a body mass index considered obese at 30.4(SD=7.0). New patient consultations were primarily referrals from other health providers internal to the MCC (71.2%), frequently primary care physicians (76%). Baseline to discharge comparisons of numeric rating scale scores for the cervical, thoracic, lumbar, sacroiliac and extremity regions all exceeded the minimally clinically important difference for reduction in musculoskeletal pain. Improvements occurred over an average of 12.7 (SD=14.3) treatments, and pain reductions were also statistically significant at p<0.05. CONCLUSION: Chiropractic services are being utilized by patients, and referring providers. Clinical outcomes indicate that services rendered decrease musculoskeletal pain in an inner city population. PMID- 26816050 TI - Harnessing spin precession with dissipation. AB - Non-collinear spin transport is at the heart of spin or magnetization control in spintronics devices. The use of nanoscale conductors exhibiting quantum effects in transport could provide new paths for that purpose. Here we study non collinear spin transport in a quantum dot. We use a device made out of a single wall carbon nanotube connected to orthogonal ferromagnetic electrodes. In the spin transport signals, we observe signatures of out of equilibrium spin precession that are electrically tunable through dissipation. This could provide a new path to harness spin precession in nanoscale conductors. PMID- 26816052 TI - Revisiting the cell biology of the acyl-ACP:phosphate transacylase PlsX suggests that the phospholipid synthesis and cell division machineries are not coupled in Bacillus subtilis. AB - PlsX is a central enzyme of phospholipid synthesis in bacteria, converting acyl ACP to acyl-phosphate on the pathway to phosphatidic acid formation. PlsX has received attention because it plays a key role in the coordination of fatty acid and phospholipid synthesis. Recently, PlsX was also suggested to coordinate membrane synthesis with cell division in Bacillus subtilis. Here, we have re investigated the cell biology of PlsX and determined that the enzyme is uniformly distributed on the membrane of most cells, but occasionally appears as membrane foci as well. Foci and homogenous patterns seem freely interconvertible but the prevalence of the uniform staining suggests that PlsX does not need to localize to specific sites to function correctly. We also investigated the relationship between PlsX and the divisome. In contrast to previous observations, PlsX's foci showed no obvious periodicity of localization and did not colocalize with the divisome. Furthermore, depletion of PlsX did not affect cell division if phospholipid synthesis is maintained by an alternative enzyme. These results suggest that coordination between division and membrane synthesis may not require physical or functional interactions between the divisome and phospholipid synthesis enzymes. PMID- 26816051 TI - The 78-kD Glucose-Regulated Protein Regulates Endoplasmic Reticulum Homeostasis and Distal Epithelial Cell Survival during Lung Development. AB - Bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity, has been linked to endoplasmic reticulum (ER) stress. To investigate a causal role for ER stress in BPD pathogenesis, we generated conditional knockout (KO) mice (cGrp78(f/f)) with lung epithelial cell-specific KO of Grp78, a gene encoding the ER chaperone 78-kD glucose-regulated protein (GRP78), a master regulator of ER homeostasis and the unfolded protein response (UPR). Lung epithelial-specific Grp78 KO disrupted lung morphogenesis, causing developmental arrest, increased alveolar epithelial type II cell apoptosis, and decreased surfactant protein and type I cell marker expression in perinatal lungs. cGrp78(f/f) pups died immediately after birth, likely owing to respiratory distress. Importantly, Grp78 KO triggered UPR activation with marked induction of the proapoptotic transcription factor CCAAT/enhancer-binding proteins (C/EBP) homologous protein (CHOP). Increased expression of genes involved in oxidative stress and cell death and decreased expression of genes encoding antioxidant enzymes suggest a role for oxidative stress in alveolar epithelial cell (AEC) apoptosis. Increased Smad3 phosphorylation and expression of transforming growth factor-beta/Smad3 targets Cdkn1a (encoding p21) and Gadd45a suggest that interactions among the apoptotic arm of the UPR, oxidative stress, and transforming growth factor-beta/Smad signaling pathways contribute to Grp78 KO-induced AEC apoptosis and developmental arrest. Chemical chaperone Tauroursodeoxycholic acid reduced UPR activation and apoptosis in cGrp78(f/f) lungs cultured ex vivo, confirming a role for ER stress in observed AEC abnormalities. These results demonstrate a key role for GRP78 in AEC survival and gene expression during lung development through modulation of ER stress, and suggest the UPR as a potential therapeutic target in BPD. PMID- 26816053 TI - Avian influenza virus H9N2 seroprevalence and risk factors for infection in occupational poultry-exposed workers in Tai'an of China. AB - To determine risk factor for H9N2 avian influenza virus (AIV) infection, a serological surveillance among both occupational poultry-exposed (OPE) workers and general humans was carried out using both haemagglutination inhibition (HI) and microneutralization (MN) assays in Tai'an, China, between 2011 and 2013. At baseline, the positive rate of anti-H9 antibody (HI and MN titers >=40) among OPE workers (51/600, 8.5%) was significantly higher than that among the general population (11/600, 1.8%). The result indicated that occupational exposure to chicken flocks was an important risk factor for H9N2 AIV infection. J. Med. Virol. 88:1453-1456, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26816054 TI - Focus on pertrochanteric fractures. PMID- 26816055 TI - Epidemiology of pertrochanteric fractures: our institutional experience. AB - PURPOSE: Hip fractures, a common manifestation of fragility fractures, represent a major cause of morbidity and mortality in the elderly population and may have devastating consequences to the patient, their family, and society thereafter. We attempted to define the epidemiology of pertrochanteric fractures treated at a large university teaching hospital in the UK and compared our findings with the national and international literature. METHODS: Between April 2008 and March 2013, we conducted a retrospective cohort study at our institution. All adult patients sustaining a proximal femoral fracture were included in our study. The following parameters were collected and evaluated: (1) demographics, (2) fracture pattern, (3) American Society of Anaesthesiologists (ASA) grade, (4) type of pre injury mobilization, and (5) method of stabilization. Our findings were then compared to the national data as published in the National Hip Fracture Database (NHFD). RESULTS: Over a period of 5 years, 3,036 proximal femoral fractures were managed at our institution, with 916 (30.2 %) being classified as pertrochanteric fractures (250 male; mean age 82.0, SD 11.2). No significant change in the incidence of pertrochanteric fractures was evident during the same period. Between 2012 and 2013, 51,705 proximal femoral fractures were recorded in England, of which 19,569 (37.8 %) were classified as pertrochanteric fractures. Comparison between pertrochanteric and intracapsular fractures with respect to their demographics did not reveal any significant difference. In female patients, the relative incidence of pertrochanteric fractures was shown to increase with age. However, this was not the case in the male population. CONCLUSIONS: The incidence of pertrochanteric fractures remained unchanged over the last 5 years. The relative incidence of pertrochanteric fractures is higher in elderly females; this may be explained by reduced bone mineral density and reduced trochanteric bone strength. Rigorous preventive treatments of osteoporosis should be considered in high-risk patients, along with improved safety measures to reduce falls. PMID- 26816056 TI - Extramedullary fixation of trochanteric hip fracture. AB - Extramedullary fixation with a sliding hip screw remains the treatment of choice for the majority of trochanteric hip fractures. Attention to surgical detail is far more important that the actual choice of implant. The fracture must be reduced to an anatomical or slight valgus position using the fracture table. Surgical exposure need not be excessive as most fractures can be reduced by closed means. The position of the lag screw is critical to achieve a central to inferior position on the anterior-posterior radiograph and a central position on the lateral view. A four-hole plate should suffice for most fractures. After surgery, weight bearing as able should be allowed. For fractures fixed correctly, wound or fracture healing complication should be rare, occurring in <5 % of cases. PMID- 26816057 TI - Intramedullary nailing in pertrochanteric fractures of the proximal femur. AB - INTRODUCTION: Pertrochanteric fractures of the proximal femur should be treated surgically, unless the medical condition of the patient does not allow it. Currently, there are two ways to fix these fractures; either with a sliding hip screw or with an intramedullary nail. However, there is much debate over which implant is the best for pertrochanteric fracture fixation. The sliding hip screw has been used over time with good clinical results. While it was true that with first generation intramedullary nails the risk of complications was higher, there is evidence supporting the superiority of intramedullary nails in these fractures when compared with sliding hip screws. This evidence is based on the good clinical results and fewer complications, due to an improvement in the design of the implants and surgical technique used by surgeons. In stable fractures, despite the method chosen for fixation, obtaining a good reduction prior to placing the implant is the most important factor that can be controlled by the surgeon. In stable fractures the surgeon experience is a strong factor to account for when choosing the type of implant. Clearly there are fracture patterns (reverse oblique and subtrochanteric extension) that benefit from the use of intramedullary devices due to the high risk of failure if plates are used. CONCLUSION: It is very important that the surgeon identifies these fractures, so the type of fixation device which is chosen achieves the greatest stability possible. The aim of this paper is not to convince the surgeon about using intramedullary nails, but highlight the potential benefits intramedullary nailing has when compared with the use of extramedullary devices. PMID- 26816058 TI - Pertrochanteric fractures: tips and tricks in nail osteosynthesis. AB - INTRODUCTION: Intramedullary fixation of intertrochanteric fractures has become the standard method of fixation especially in unstable fracture types. Even though there have been developments on implant design and technology, the surgical technique of reduction and implant positioning remains the mandatory factor in treating these fractures successfully. The advantages of nailing in the mainly elderly patients sustaining intertrochanteric femur fractures are a short lever arm and a lateral support in the trochanter supplied by the nail. The disadvantages are that it is often harder to achieve a closed reduction of a displaced fracture and to maintain the reduction with the intramedullary implant. TIPS AND TRICKS: To obtain and maintain anatomic reduction and a secure fracture fixation, the surgical approach and fixation technique is of great importance. It starts with correct patient positioning, fracture reduction (accounting for varus dislocation and dislocation of flexed fragments), choosing the correct nail entry point and perfect lag screw positioning within the head-neck fragment and distal locking. To maintain the reduction achieved intraoperatively, the decision has to be made to use a cerclage wiring or to tolerate fracture gaps in the metaphyseal area. Intraoperative controlled compression of the neck or the subtrochanteric area is of great importance to reduce delayed unions or nonunions. Intramedullary fixation of unstable per-, inter- or subtrochanteric fractures shows biomechanical advantages compared to extramedullry fixation techniques. Even though there have been several amendments and developments of implants, a better implant does not compensate for an inadequate surgical approach or deficient surgical techniques which are paramount for successful treatment. When fixing fractures with intramedullary nailing systems, the surgeon should always try to achieve anatomic reduction and a perfect implant positioning to allow immediate full weight bearing without an increased risk of cut-out, non-union and implant failure. PMID- 26816059 TI - A holistic hip fracture approach: individualized diagnosis and treatment after surgery. AB - Secondary fracture prevention is of paramount importance in the clinical management of patients with hip fractures. However, in contrast to the excellent surgical care provided to these patients in the Western hemisphere and despite good medical options, causative treatment of the underlying osteopathy causing skeletal fragility remains an unmet medical need that urgently needs to be improved. This calls for a concerted action between orthopedic/trauma surgeons and osteologists, as outstanding hospitals not only treat fragility fractures, but also prevent fractures from recurring. Aiming for a holistic hip fracture approach, in this work we highlight aspects of (a) improved risk assessment and differential diagnosis, (b) optimized basic medical care, and PMID- 26816060 TI - Primary prosthetic replacement in per- and intertrochanteric fractures. AB - PURPOSE: Hip arthroplasty is rarely indicated in the treatment of per- and intertrochanteric femur fractures. Although the majority of fractures are amenable to closed- or open reduction and internal fixation (CRIF/ORIF), in some patients the complexity of the fracture or other patient-related factors may cause the orthopaedic surgeon to consider arthroplasty as the treatment of choice. Decision-making is challenging, and a reliable score has not yet been established. RESULTS: Reviewing literature, several predictors of inferior outcome after CRIF/ORIF in per- and intertrochanteric fractures such as age, gender, poor bone quality, hip osteoarthritis, operation time and postoperative weight-bearing restrictions have been identified. Based on the literature review, a novel Hamburg Per- and Intertrochanteric Fracture Score (HPIFS) is proposed to support decision-making for per- and intertrochanteric fracture treatment. CONCLUSIONS: CRIF/ORIF remain the workhorses in per- and intertrochanteric fracture management. Arthroplasty offers an advantageous treatment option for a well-defined patient and fracture collective. The HPIFS might support the decision-making process. PMID- 26816061 TI - Pooled preventable death rates in trauma patients : Meta analysis and systematic review since 1990. AB - PURPOSE: To estimate the pooled PDRs (preventable death rates) with articles being published since 1990, and compare the differences of PDRs over time and according to the evaluation approaches to determine preventable deaths. METHODS: Articles concerning preventable deaths of trauma patients published between 1990 and 2013 were systematically reviewed, and the pooled PDRs with 95 % confidence intervals were estimated using meta-analysis. It was also observed whether the PDRs differed over time and according to the evaluation approaches employed for determining preventable deaths. RESULTS: Twenty seven articles were identified through bibliographic searches using PUBMED with the keywords of 'preventable deaths', 'the cause of deaths' and 'trauma'. Mean ages of the trauma patients in the selected articles ranged from 32.9 to 58 years old and 72 % were male on average. The pooled PDR was estimated as 0.20 with 95 % CI (0.16, 0.25) with a p value of 0.0001, and the differences of PDRs over time and according to the employed approaches were not statistically significant with p-values of 0.06 and 0.99, respectively. However, PDRs determined by statistical approaches alone showed greater dispersion in comparison with the 'panel review approach'. CONCLUSIONS: This article provided some insights about the trauma care system by computing the pooled estimate of PDRs over the past 23 years as an indicator. The pooled PDR was estimated as approximately 20 %, with no statistical significance of differences in PDRs over time or by the evaluation methods employed. That left us still room for improvement in trauma care system despite our efforts to reduce PDRs. In addition, when 'statistical approaches' are applied alone to estimate PDRs, we recommend that statistical methods should be applied with caution when the characteristics of trauma patients are heterogeneous. The optimal approach might be to combine both statistical and panel review approaches instead of employing a single approach. PMID- 26816062 TI - The exponential function transforms the Abbreviated Injury Scale, which both improves accuracy and simplifies scoring. AB - PURPOSE: We present here the exponential function which transforms the Abbreviated Injury Scale (AIS). It is called the Exponential Injury Severity Score (EISS), and significantly outperforms the venerable but dated New Injury Severity Score (NISS) and Injury Severity Score (ISS) as a predictor of mortality. METHODS: The EISS is defined as a change of AIS values by raising each AIS severity score (1-6) by 3 taking a power of AIS minus 2 and then summing the three most severe injuries (i.e., highest AIS), regardless of body regions. EISS values were calculated for every patient in two large independent data sets: 3,911 and 4,129 patients treated during a 6-year period at the Class A tertiary hospitals in China. The power of the EISS to predict mortality was then compared with previously calculated NISS values for the same patients in each of the two data sets. RESULTS: We found that the EISS is more predictive of survival [Zhejiang: area under the receiver operating characteristic curve (AUC): NISS = 0.932, EISS = 0.949, P = 0.0115; Liaoning: AUC: NISS = 0.924, EISS = 0.942, P = 0.0139]. Moreover, the EISS provides a better fit throughout its entire range of prediction (Hosmer-Lemeshow statistic for Zhejiang: NISS = 21.86, P = 0.0027, EISS = 13.52, P = 0.0604; Liaoning: NISS = 23.27, P = 0.0015, EISS = 15.55, P = 0.0164). CONCLUSIONS: The EISS may be used as the standard summary measure of human trauma. PMID- 26816063 TI - Trauma care in Scotland: effect of rurality on ambulance travel times and level of destination healthcare facility. AB - AIM: The aim of this study was to determine the effect of rurality on the level of destination healthcare facility and ambulance response times for trauma patients in Scotland. METHODS: We used a retrospective analysis of pre-hospital data routinely collected by the Scottish Ambulance Service from 2009-2010. Incident locations were categorised by rurality, using the Scottish urban/rural classification. The level of destination healthcare facility was coded as either a teaching hospital, large general hospital, general hospital, or other type of facility. RESULTS: A total of 64,377 incidents met the inclusion criteria. The majority of incidents occurred in urban areas, which mostly resulted in admission to teaching hospitals. Incidents from other areas resulted in admission to a lower-level facility. The majority of incidents originating in very remote small towns and very remote rural areas were treated in a general hospital. Median call out times and travel times increased with the degree of rurality, although with some exceptions. CONCLUSIONS: Trauma is relatively rare in rural areas, but patients injured in remote locations are doubly disadvantaged by prolonged pre hospital times and admission to a hospital that may not be adequately equipped to deal with their injuries. These problems may be overcome by the regionalisation of trauma care, and enhanced retrieval capability. PMID- 26816064 TI - Assessing the gap between the acute trauma workload and the capacity of a single rural health district in South Africa. What are the implications for systems planning? AB - INTRODUCTION: This study focuses on a single rural health district in South Africa, and attempts to establish the burden of disease and to review the capacity of the district hospitals to deal with this load. METHODS: Ethical approval to undertake this study was obtained from both the University of Kwa Zulu Natal and the Department of Health. The audit was performed over a 6-month period in the four district hospitals of rural Sisonke District. There were four components to this audit. 1. Information on the hospital incidence of acute trauma in Sisonke was also sourced from the epidemiology unit of the Department of Health in Pietermaritzburg 2. Each of the district hospitals was visited and the medical manager was interviewed. The medical manager was asked to complete the World Health Organization's Tool for Situational Analysis to Assess Emergency and Essential Surgical Care. (SAT). 3. The operative registers were reviewed to determine the number of index cases for trauma. This information was used to determine the unmet need of acute trauma in the district. 4. Each hospital was classified according to the Trauma Society of South Africa (TSSA) guidelines for levels of trauma care. RESULTS: The annual incidence of trauma in the Sisonke District is estimated to be 1,590 per 100,000 population. Although there appeared to be adequate infrastructure in the district hospitals, the SAT revealed significant deficits in terms of capacity of staff to adequately treat and triage acute trauma patients. There is a significant unmet need for trauma care in Sisonke. The four district hospitals can best be classified as Level IV centers of trauma care. CONCLUSION: There is a significant burden of trauma in the Sisonke District, yet the capacity to deal with this burden is inadequate. Although the physical infrastructure is adequate, the deficits relate to human resources. The strategic choices are between enhancing the district hospitals' capacity to deal with acute trauma, or deciding to bypass them completely and deliver all acute trauma patients to large regional trauma centers. If the first option is chosen, urgent intervention is required to build up the human resource capacity of district hospitals. PMID- 26816065 TI - Serum lipase for assessment of pancreatic trauma. AB - PURPOSE: Pancreatic enzymes are routinely measured during reception of trauma patients to assess for pancreatic injury despite conflicting evidence on their utility. The aim of this study was to investigate the utility of routine initial serum lipase measurement for the diagnosis of acute pancreatic trauma. MATERIALS AND METHODS: Lipase measurements were introduced as part of the trauma pathology panel and requested on all patients who presented to an adult major trauma service and met trauma call-out criteria. Clinical records of these patients were extracted from the trauma registry and retrospectively reviewed. The performance of an initial serum lipase level measured on presentation to detect pancreatic trauma was determined. RESULTS: There were 2,580 patients included in the study, with 17 patients diagnosed with pancreatic trauma. An elevated lipase was recorded in 390 patients. Statistically significant associations were observed for elevated lipase in patients with pancreatic trauma, head injury, acute alcohol ingestion and massive blood transfusion. As a test for pancreatic trauma, an abnormal serum lipase result had a specificity of 85.3 % (95 % CI 83.8-86.6), sensitivity of 76.5 % (95 % CI 49.8-92.2), positive predictive value of 3.3 % (95 % CI 1.8-5.8) and negative predictive value of 99.8 % (95 % CI 99.4-99.9). Higher cut-offs of serum lipase did not result in better performance. CONCLUSIONS: A normal serum lipase result can be a useful adjunct to exclude pancreatic injury. A positive lipase result, regardless of the cut-off used, was not reliably associated with pancreatic trauma, and should not be used to guide further assessment. PMID- 26816066 TI - Vascular injuries following blunt polytrauma. AB - INTRODUCTION: Motor vehicle collisions account for the majority of blunt vascular trauma. Much of the literature describes the management of these injuries in isolation, and there is little information concerning the incidence and outcome in patients suffering multiple trauma. This study was undertaken to describe the spectrum of blunt vascular injuries in polytrauma patients. PATIENTS AND METHODS: All patients who had sustained blunt vascular trauma over a 6-year period (April 2007-March 2013) were identified from a prospectively gathered database at the Level I Trauma Unit, Inkosi Albert Luthuli Central Hospital, Durban, South Africa. The retrieved data consisted of age, sex, mechanism of injury, referral source, Injury Severity Score (ISS), New Injury Severity Score (NISS), time from injury to admission, surgical intervention and outcome. The initial investigation of choice for patients sustaining multiple injuries was computed tomography (CT) angiography if they were physiologically stable, followed by directed angiography if there was doubt concerning any vascular lesion. If technically feasible, endovascular stenting was the preferred option for both aortic and peripheral vascular injuries. RESULTS: Of 1,033 patients who suffered blunt polytrauma, 61 (5.9 %) sustained a total of 67 blunt vascular injuries. Motor vehicle collisions accounted for 92 % of the injuries. The median ISS was 34 [interquartile range (IQR) 24-43]. The distribution of blunt vascular injuries was extremity (21), thorax (20), abdomen and pelvis (19), and head and neck (7). Endovascular repair was employed in 12 patients (ten blunt aortic injury, one carotid-cavernous sinus fistula, one external iliac artery). Of the extremity injuries, primary amputation was undertaken in 8 (38.1 %) and secondary amputation in 2 (9.5 %). The total amputation rate was 48 %. There were 17 (28.3 %) deaths, of which 11 (64.7 %) were directly attributable to the vascular injury and 6 (35.3 %) of these occurred on the operating table from exsanguination, the majority from injuries to the abdominal vena cava. CONCLUSIONS: Blunt vascular injury is uncommon in the patient with multiple trauma but confers substantial morbidity and mortality. In those cases with peripheral injuries, delays in referral to definitive care frequently exceed the ischaemic time, resulting in a high rate of amputations. Central injuries, especially those of the vena cava, account for the majority of directly attributable deaths. PMID- 26816067 TI - Massive haemorrhage following minimally displaced pubic ramus fractures. AB - BACKGROUND: Fractures of the pubic rami are the most frequent osteoporotic pelvic fracture. Although generally innocuous, epidemiologic research demonstrated a decreased survival in patients with pubic rami fractures compared to healthy controls. Sporadic cases of potentially lethal bleedings have been reported. The aim of this study was to report a consecutive series and review of the literature of patients with severe bleeding following minimally displaced pubic ramus fractures. MATERIALS AND METHODS: We report on four cases who presented at our emergency department in 2012 and 2013. A systematic review was performed to find other cases of pubic ramus fracture with severe bleeding from the literature. RESULTS: Four elderly patients presented with severe bleeding following os pubis fracture after trivial falls from ground level. Successful arterial embolisation was performed in two cases. These patients were discharged in good clinical condition. Two other patients were refrained from further treatment due to a pre existing poor prognosis. Twenty-two additional cases were found in the literature. Successful arterial embolisation was performed in 20 cases, of whom 17 survived. CONCLUSIONS: Severe bleeding, mostly secondary to corona mortis avulsions, is a rare but potentially lethal complication of pubic ramus fractures. Physicians should be aware of this complication and actively look for symptoms of bleeding. Super-selective arterial embolisation seems safe and highly effective to control bleeding secondary to pubis rami fractures in elderly patients. PMID- 26816068 TI - Lower extremity fractures in falls. AB - INTRODUCTION: Lower extremity fractures are very common in victims of falls. These fractures are usually associated with other bodily injuries and can lead to permanent disability if appropriate management is not provided. The aim of this study was to evaluate the incidence and outcomes of associated injuries in victims of falls with lower extremity fractures. METHODS: This is a retrospective review (1995-2006) of all fall-related trauma patients evaluated at our Level I trauma center. Injuries were categorized as: isolated femur fractures (FF), isolated tibia fractures (TF), and both femur and tibia fractures (FTF). Data were analyzed for differences in patterns of injury, associated fractures and injuries, and mortality and morbidity according to age groups within patients with minor body injuries expressed by Abbreviated Injury Score (AIS) < 3. RESULTS: Three hundred and thirty-two patients (64.8 %) had FF, 164 patients (32 %) had TF, and 16 patients (3.2 %) presented with FTF. The incidence of severe trauma was 9.4 % (Injury Severity Score, ISS > 25). A higher incidence of ISS > 25 was observed in patients with FF. Increased mortality was observed in the elderly group, especially in patients with an isolated femur fracture. CONCLUSION: Patients with a combination of femur and tibia fractures have a significantly higher risk of associated injuries compared to patients with either a femur or a tibia fracture. Elderly patients (>=65 years of age) have higher morbidity and mortality compared to younger patients after falls. Clinicians evaluating these patients should be aware of these injury patterns. Further studies assessing the impact of age and pattern of injury in patients following falls are warranted. PMID- 26816069 TI - More adverse events than expected in the outcome after use of the reamer irrigator-aspirator. AB - PURPOSE: The reamer-irrigator-aspirator (RIA) system is described as having high success rates and only few complications. The RIA was originally designed to ream the intramedullary canal in a single step prior to the placement of an intramedullary nail for femur fixation. Its purpose was to collect and evacuate marrow contents during reaming to prevent embolism into the systemic circulation. Marrow evacuation is also used to stimulate healing in nonunion fractures, segmental bone defects, and osteomyelitis. Despite the described success rates, we experienced severe adverse events. Our aim was to describe these events and point out possible complications. METHODS: A retrospective study of all consecutive patients treated for nonunion fractures, bone defects, or osteomyelitis from October 2007 to March 2010. All patients were treated with the RIA system. We analyzed demographic characteristics, consolidation on X-rays, time from injury to healing, complications, and postoperative pain caused by the reaming procedure. RESULTS: We included 32 patients (21 males) with an average follow-up of 277 days. Successful healing was achieved in 66 % of all patients, and 18 % suffered from postoperative pain. A complication due to the use of the RIA system was registered in 31 % of the patients. Recorded complications were bone defects, signs of lung embolism, a myocardial infarction, and fissure fractures. CONCLUSIONS: The RIA system has benefits in the treatment of nonunion and osteomyelitis defect, but is not without risk. Meticulous surgical technique is mandatory and peroperative constant monitoring of patients and the assembled device is mandatory. PMID- 26816070 TI - Acute traumatic fractures to the craniovertebral junction: preliminary experience with the "MILD" score scale. AB - PURPOSE: Traumatic fractures to the craniovertebral junction (CVJ) are rare events requiring complex clinical management. Several classification systems are currently in use; however, recent improvements of junctional knowledge has focused attention on the role of ligaments and membranes in vertebral biomechanical stability. The aim of this study was to present our preliminary experience with the "MILD" score scale, which should allow fast and effective classification of all CVJ traumatic fractures based on vertebral instability in the acute setting. METHODS: A prospective study was conducted on 38 consecutive patients with 43 traumatic junctional fractures identified by computed tomography (CT) scan in the acute trauma phase. The MILD scale was applied to all fractures, and a score was obtained for each patient. All cases underwent magnetic resonance imaging (MRI) to assess the anatomical integrity of ligaments and membranes. RESULTS: Twenty-seven patients (71 %) were classified as MILD type 1 (0-1 points), showed a negative MRI, and healed with conservative treatment. Eight patients (21 %) were classified as MILD type 2 (2 points) and showed modest indirect signs of ligamentous injuries. Four of these patients healed with conservative treatment, while three patients underwent surgery due to wide bone fracture fragment displacement. Three patients (8 %) were classified as MILD type 3 (3 points), all of whom showed extensive ligamentous damage and underwent surgery. CONCLUSIONS: The close association between the MILD scale and spinal instability is promising, although further studies are warranted in order to confirm our preliminary data. PMID- 26816071 TI - The role of surgery in the management of "body packers". AB - INTRODUCTION: The concealment of packets of illegal substances within body cavities is a common technique for drug smuggling worldwide. The goal of our study was to analyze the results of conservative treatment of "body packers", indications for surgical intervention, and postoperative morbidity. METHODS: This is a retrospective study of patients admitted to our hospital and diagnosed as body packers. The diagnostic protocol included an abdominal X-ray and urinalysis for toxic substances. Only patients with gastrointestinal symptoms, signs of intoxication, or a positive urinalysis were admitted for observation. Conservative management included bowel rest and serial abdominal radiographs to confirm the passage per rectum of all foreign bodies. Asymptomatic patients were given laxatives in the emergency department (ED) to promote bowel movements and were not admitted to the hospital. RESULTS: A total of 763 body packers were admitted to the hospital, all of whom were initially treated conservatively. Of these patients, 47 (6 %) developed complications: 28 with bowel obstruction, three with bowel perforation, and 16 with substance intoxication. In patients developing complications, urinalysis for toxic substances was negative in 19 (40 %). Sixteen (34 %) patients who developed complications were successfully managed nonoperatively. Three (6 %) other patients died before surgery: two deaths resulted from acute toxicity (one of them with an acute onset and a negative urinalysis) and the third patient died of bowel perforation. Laparotomy was required in 28 (3.5 %) body packers admitted for observation. Enterotomy and/or gastrotomy to remove the packets were the most frequently performed procedures. Postoperative morbidity occurred in 57 % of patients, with wound infection being the most frequent complication. CONCLUSIONS: Conservative management was effective in 94 % of symptomatic patients. A laparotomy was required in only 3.5 % of cases. The mortality rate in this series was low, resulting from either severe cocaine poisoning from ruptured packets or bowel perforation. PMID- 26816072 TI - Incidence and characteristics of distal radial fractures in an urban population in The Netherlands. AB - The increasing incidence of distal radius fracture is thought to be due to the aging population. Surprisingly, some authors have reported a decrease in the incidence of distal radius fracture. Moreover, the type-specific incidence of distal radial fracture classified according to fracture severity is not well documented. The aim of this population-based study was to estimate the overall and type-specific incidences of distal radius fracture in a urban population in The Netherlands. During 2009, all persons aged >=18 years old with an acute distal radius fracture in two hospitals in The Netherlands were prospectively registered. In 2009, the mid-year study population consisted of 245,559 inhabitants >=18 years old. Fractures were categorized according to the AO classification. 494 patients with acute distal radius fractures were registered in the two participating hospitals during the 1-year study period. The overall incidence of distal radius fracture was 20 per 10,000 person-years. Among women, the incidence rate increased from the age of 50 and reached a peak of 124 per 10,000 person-years in women 80 years and older. Among men, the incidence rate was low until the age of 80 years and older, and reached a peak of 24 per 10,000 person-years. The incidence rate among women between 50 and 79 years was 54/10,000 person-years. Extra-articular AO type A fractures were most common among all age groups, comprising 50 % of all fractures (40 % in men and 53 % in women). The overall incidence rate of distal radius fracture was 20 per 10,000 person-years. This incidence increases with age for both women and men. A lower incidence rate among women 50-79 years of age was found than previously reported, which may indicate a declining incidence in this age group. Extra-articular AO type A fractures were the most common fracture types. PMID- 26816073 TI - Efficacy of N-acetylcysteine on neuroclinical, biochemical, and histopathological parameters in experimental spinal cord trauma: comparison with methylprednisolone. AB - BACKGROUND: N-acetylcysteine (NAC) is an antioxidant agent that has been shown to have beneficial effects when treating various diseases. The aim of this study was to investigate the effects of NAC on spinal cord injury in an experimental rat model. METHODS: A total of 48 adult male wistar albino rats were divided into six groups. Group C included the control rats, group L included the rats that underwent laminectomy, and group T included the rats in which spinal cord trauma was induced by the weight-drop method after laminectomy. Groups M (the methylprednisolone group), N (the NAC group), and MN (the methylprednisolone + NAC group) were the treatment groups. In the fourth group (group M), 30 mg/kg methylprednisolone (MP) was administered as a bolus intraperitoneally (IP), and a standard MP treatmentat a dose of 5.4 mg/kg was applied for 24 h. In the fifth group (group N), only 300 mg/kg NAC was administered as a bolus IP. In the sixth group (group MN), the standard MP treatment and a single 300 mg/kg dose of NAC were administered as a bolus IP. The motor functions of the rats were evaluated on the 1st, 7th, and 14th days using the inclined plane test defined by Rivlin and Tator and the motor scale defined by Gale et al. Spinal cord samples were obtained on the 14th day. The samples were evaluated using pathological and biochemical analysis. RESULTS: In the neuroclinical assessment, no differences were observed between groups T and M in terms of motor improvement. However, statistically significant differences were observed between group T and groups N and MN (p < 0.001, p = 0.01, respectively). Statistically significant differences were also seen between group M and groups N and MN on the 1st and 7th days (p < 0.017, p < 0.01, respectively). Additionally, when groups N and MN were compared with groups T and M,the pathological and biochemical analyses were found to be statistically different (p < 0.05, p < 0.001, respectively). CONCLUSION: It was concluded that NAC treatment and the combined NAC + MP treatment may be more useful for healing in rats with experimental spinal cord injury in terms of neuroclinical, pathological, and biochemical results than MP-only therapy. PMID- 26816074 TI - The prognostic value of plasma Delta-copeptin levels in patients with isolated traumatic brain injury. AB - PURPOSE: Traumatic brain injury (TBI) is one of the most common causes of death among trauma patients. Earlier prediction of possible poor neurological outcomes, even upon admission to the emergency department, may help to guide treatment. The aim of this prospective study was to assess the predictive value of plasma copeptin levels for early morbidity and mortality in patients with isolated TBI. METHODS: This prospective study comprised 53 patients who were admitted to the emergency department with isolated TBI. Forty-two of these patients (group I) survived at least 1 month after the TBI; the other 11 (group II) did not. Plasma levels of copeptin were measured in these TBI patients at admission and 6 h after trauma, and were compared with those of healthy volunteers (group III). RESULTS: At admission, the copeptin levels of the TBI patients (groups I and II combined) were not statistically significantly different from those of the control group (III). The copeptin levels 6 h after trauma were also not statistically significantly different from those at admission. Delta-Copeptin levels (the difference between the copeptin level at the 6th hour after trauma and that at admission) were higher in the patients who died within a month of the TBI. Further, Delta-copeptin levels were higher in patients who showed no improvement in the modified Rankin score when compared with patients with an improved modified Rankin score. The best cutoff point for Delta-copeptin was 0.51 ng/ml for predicting mortality and 0.23 ng/ml for predicting improvement in the modified Rankin score. CONCLUSIONS: Plasma Delta-copeptin levels may help physicians predict the prognoses of patients suffering from traumatic brain injury. PMID- 26816075 TI - Posterior fixation of type IV humeral capitellum fractures with fully threaded screws in adolescents. AB - PURPOSE: Humeral capitellum fractures comprise approximately 1% of all elbow fractures. In this study, we examined the clinical, radiographic, and functional outcomes following operative stabilization of Bryan and Morrey type IV fractures of the capitellum in adolescents. We applied headless cannulated screws in a posteroanterior direction without damaging the articular cartilage surface of the fractures. METHODS: Eight adolescent patients (six male, two female) with a mean age of 15 +/- 2.1 years (range 13-18 years) were treated for type IV (McKee) humerus capitellum fractures. In the preoperative radiological evaluation, anteroposterior and lateral radiographs and computed tomography (CT) images were performed. A lateral surgical approach was used, and cannulated fully threaded headless screws were applied in a posteroanterior direction as fixation materials in the fracture reduction. The Mayo Elbow Performance Score was used in the evaluation of elbow joint functions. RESULTS: Patients were followed up for a mean of 24.6 months. Fracture union was achieved at a mean of 5 +/- 0.92 weeks (range 4-6 weeks). The mean elbow extension flexion arc was 135 degrees +/- 13.47 degrees (range 110 degrees -150o) and the mean pronation supination arc was 156 degrees +/- 4.43 degrees (150 degrees -160 degrees ). In one patient, there was nonconformity in the humerus trochlea and in another patient, there was keloid formation on the surgical scar. All patients attained excellent results according to the Mayo Elbow Performance Score. CONCLUSIONS: In the treatment of type IV capitellum fractures in adolescents, open reduction with a lateral surgical approach and fixation using posteroanterior directed, cannulated, fully threaded, headless screws is a reliable method to achieve a pain-free functional elbow joint. PMID- 26816076 TI - Current issues with lower extremity amputations in a country at war: experience from the National Military Hospital of Kabul. AB - PURPOSE: Management practices associated with war-related amputations in countries at war may be different from the recommendations of occidental Health Force Services due to the high numbers of wounded persons to treat in precarious conditions. This observational retrospective study documents the current management of local lower extremity amputees in Afghanistan. Surgical practices, with or without delayed primary closure (DPC), and prosthetic rehabilitation issues are analyzed. METHODS: This retrospective study was conducted in the National Military Hospital (NMH) of Kabul from May 2011 to November 2011. Fifty four Afghan patients who underwent a lower extremity combat-related amputation were included. Ten of them sustained a bilateral amputation. RESULTS: Injuries were caused by improvised explosive devices (IEDs) or mines in 48 cases, bullets in three cases, and exploding shell fragments in three cases. Of the 64 amputations studied, 46 were open length preserving amputations and primary closure (PC) was applied in 18 cases. Patients were reviewed with a mean follow up of 5.4 months (range 1-28 months). In the DPC group, secondary closure was performed with a mean time of 18.7 days (range 4-45 days) from injury. The proportion of infectious complications seemed to be higher in the PC group (5/18) than in the DPC group (3/46), but it was only a statistical trend (p = 0.1). Forty-three patients were not prosthetic fitted at the last follow-up. CONCLUSION: This study supports the surgical strategy of a two-stage procedure for lower limb amputations in countries at war, but underlines the problems of late secondary closure and prosthetic fitting related to decreased sanitary conditions. PMID- 26816077 TI - Should prehospital resuscitative thoracotomy be incorporated in advanced life support after traumatic cardiac arrest? AB - The survival of traumatic cardiac arrest patients poses a challenge for Emergency Medical Services initiating advanced life support on-scene, especially with regard to having to decide immediately whether to initiate prehospital emergency thoracotomy. Although the necessity for carrying out the procedure remains a cause for debate, it can be life-saving when performed with the correct indications and approaches. PMID- 26816079 TI - ESTES NEWS 3.2014. PMID- 26816078 TI - Erratum to: Efficacy of N-acetylcysteine on neuroclinical, biochemical, and histopathological parameters in experimental spinal cord trauma: comparison with methylprednisolone. PMID- 26816080 TI - 33rd Meeting of the Pediatric Section of the German Society of Trauma Surgeons (DGU). PMID- 26816081 TI - D-SAL and NAP: Two Peptides Sharing a SIP Domain. AB - NAPVSIPQ (NAP) and all D-amino acid SALLRSIPA (D-SAL) are neuroprotective peptides derived from activity-dependent neuroprotective protein (ADNP) and activity-dependent neurotrophic factor (ADNF), respectively. Both proteins were shown to protect against cognitive impairment, using different animal models and to increase neuronal survival following exposure to neurotoxins. NAP was extensively tested and found to increase microtubule stability, protect axonal transport, and inhibit apoptosis. Here, we aimed to further evaluate and correlate effects at the behavioral level, in a rat model of diabetes. Diabetes is primarily a metabolic disorder which presents secondary neurological manifestations. Diabetes induces peripheral nervous system damage which is translated into impaired sensory perception and is termed diabetic neuropathy. Diabetes-related central nervous system damage causes cognitive decline. The behavioral study aimed to evaluate the effect of NAP and D-SAL on peripheral neuropathy and cognitive decline. Peripheral neuropathy was tested by measuring the response to a thermal stimulus, and cognitive ability was measured by a social memory test and a spatial memory test using long- and short-term dependent tasks and a reference memory task. Results indicated an immediate sensory neuropathy in the diabetic model, which was prevented by both peptides and a later neuropathic phase, prevented only by NAP treatment. Cognitive tests revealed impaired performance in both social and spatial memory tests in the diabetes model. Each of the peptides improved different aspects of cognitive behavior, with NAP being more potent than D-SAL. Mechanistically, both NAP and SAL contain a SIP (SxIP) domain that has been shown to interact with microtubule end-binding proteins (EBs). Specifically, we have previously shown a direct interaction of NAP with EB1 and EB3; we have further shown an interaction of the NAP-derived 4 amino acid SKIP peptide with EB3, stimulating axonal transport. Interestingly, the all D-amino acid peptide, D-SKIP, only partially mimicked SKIP activity. Our current results implicate D-SAL activity with potentially reduced potency compared to NAP, partially mimicking the SKIP/D-SKIP results and placing the SIP (SxIP) motif as a central focus for microtubule-based neuroprotection. PMID- 26816082 TI - Microtubule-Tau Interaction as a Therapeutic Target for Alzheimer's Disease. PMID- 26816083 TI - Meta-Analysis of the Efficiency and Prognosis of Intracranial Aneurysm Treated with Flow Diverter Devices. AB - Flow diverter devices (FDDs) are increasingly used in the treatment of intracranial aneurysm. The safety and feasibility of FDD were assessed in published literature. In accordance with strict inclusion criteria, Medline, Embase, Cochrane, China National Knowledge Infrastructure, and Web of Science databases were searched for literature that covers a period until February 2015. The baseline characteristics of patients, aneurysms, aneurysm occlusion, morbidity, and mortality were also collected. A meta-analysis was conducted using STATA 12.0, and a chi-squared test was performed to evaluate whether statistically significant differences existed between complications and mortality of aneurysm patients. Finally, a total of 48 studies were selected, including 2508 patients with 2826 aneurysm cases. The mean follow-up interval is 6.3 months, and the aneurysm occlusion rate is 77.9 % (95 % CI 73.8-81.9, I (2) = 43.4 %). The total morbidity and mortality rates are 9.8 and 3.8 %, respectively. The rates of spontaneous rupture and intraparenchymal hemorrhage are 2.0 and 2.5 %, respectively. The rate of ischemic stroke is 5.5 %. The morbidity and mortality rates of giant aneurysms are significantly higher than those of small and large aneurysms (chi (2) = 56.96, p < 0.05; chi (2) = 14.88, p < 0.05). The morbidity rates of posterior aneurysms are significantly higher than those of anterior (chi (2) = 11.29, p < 0.05) and unruptured aneurysms (chi (2) = 10.36, p < 0.05), respectively. The publication bias of aneurysm occlusion was detected by Begg's rank, and the corrected result is less than 0.05. Our meta-analysis suggests that the treatment of intracranial aneurysm with FDD is feasible and effective with a high occlusion rate, acceptable morbidity, and mortality. However, the morbidity or mortality of giant aneurysms is still high. PMID- 26816084 TI - Urinary N-methylnicotinamide and beta-aminoisobutyric acid predict catch-up growth in undernourished Brazilian children. AB - Enteric infections, enteropathy and undernutrition in early childhood are preventable risk factors for child deaths, impaired neurodevelopment, and later life metabolic diseases. However, the mechanisms linking these exposures and outcomes remain to be elucidated, as do biomarkers for identifying children at risk. By examining the urinary metabolic phenotypes of nourished and undernourished children participating in a case-control study in Semi-Arid Brazil, we identified key differences with potential relevance to mechanisms, biomarkers and outcomes. Undernutrition was found to perturb several biochemical pathways, including choline and tryptophan metabolism, while also increasing the proteolytic activity of the gut microbiome. Furthermore, a metabolic adaptation was observed in the undernourished children to reduce energy expenditure, reflected by increased N-methylnicotinamide and reduced beta-aminoisobutyric acid excretion. Interestingly, accelerated catch-up growth was observed in those undernourished children displaying a more robust metabolic adaptation several months earlier. Hence, urinary N-methylnicotinamide and beta-aminoisobutyric acid represent promising biomarkers for predicting short-term growth outcomes in undernourished children and for identifying children destined for further growth shortfalls. These findings have important implications for understanding contributors to long-term sequelae of early undernutrition, including cognitive, growth, and metabolic functions. PMID- 26816085 TI - Evidence for an imbalance between tau O-GlcNAcylation and phosphorylation in the hippocampus of a mouse model of Alzheimer's disease. AB - Intracellular accumulation of hyperphosphorylated tau protein is linked to neuronal degeneration in Alzheimer's disease (AD). Mounting evidence suggests that tau phosphorylation and O-N-acetylglucosamine glycosylation (O GlcNAcylation) are mutually exclusive post-translational modifications. O GlcNAcylation depends on 3-5% of intracellular glucose that enters the hexosamine biosynthetic pathway. To our knowledge, the existence of an imbalance between tau phosphorylation and O-GlcNAcylation has not been reported in animal models of AD, as yet. Here, we used triple transgenic (3xTg-AD) mice at 12 months, an age at which hyperphosphorylated tau is already detected and associated with cognitive decline. In these mice, we showed that tau was hyperphosphorylated on both Ser396 and Thr205 in the hippocampus, and to a lower extent and exclusively on Thr205 in the frontal cortex. Tau O-GlcNAcylation, assessed in tau immunoprecipitates, was substantially reduced in the hippocampus of 3xTg-AD mice, with no changes in the frontal cortex or in the cerebellum. No changes in the expression of the three major enzymes involved in O-GlcNAcylation, i.e., glutamine fructose-6-phosphate amidotransferase, O-linked beta-N-acetylglucosamine transferase, and O-GlcNAc hydrolase were found in the hippocampus of 3xTg-AD mice. These data demonstrate that an imbalance between tau phosphorylation and O-GlcNAcylation exists in AD mice, and strengthens the hypothesis that O-GlcNAcylation might be targeted by disease modifying drugs in AD. PMID- 26816086 TI - Pharmacological treats for SUMO addicts. AB - Non-oncogene addiction exploits cancer vulnerabilities resulting from altered cellular signaling pathways in response to oncogenic mutations that are not directly druggable. In this perspective, we address recent findings showing how the SUMOylation cascade provides a synthetic lethal target in the context of different malignant transformations. Functional genomics screens have revealed that the activation of oncogenes such as NOTCH1, MYC or KRAS generates a cancer specific dependency on SUMOylation. Pharmacological targeting of the SUMOylation cascade induces cancer cell death in these settings, suggesting potential therapeutic applications in oncology. However, the physicochemical properties of the few currently available SUMOylation inhibitors preclude clear-cut investigations and clinical testing. We therefore encourage the development of better chemical probes targeting this multifaceted post-translational modification. Such optimized molecules would enable proof of concept studies to evaluate the therapeutic potential of non-oncogene addiction to SUMO. PMID- 26816087 TI - Jumonji histone demethylases as emerging therapeutic targets. AB - The methylation status of lysine residues in histones determines the transcription of surrounding genes by modulating the chromatin architecture. Jumonji domain-containing histone-lysine demethylases (Jmj-KDMs) remove the methyl moiety from lysine residues in histones by utilizing Fe(2+) and alpha ketoglutarate. Since genetic alterations in Jmj-KDMs occur in various human cancers, the roles of Jmj-KDMs in cancer development and progression have been investigated, but still controversial. The KDM7 subfamily, which belongs to the Jmj-KDM family, is an emerging class of transcriptional coactivators because its members erase the repressive marks H3K9me2/1, H3K27me2/1, and H4K20 me1. Recently, KDM7C (alternatively named PHF2) was discovered as a new KDM7 member and identified to play a tumor-suppressive role through the reinforcement of p53 driven growth arrest and apoptosis. In this article, we generally reviewed the roles of Jmj-KDMs in human cancers and more discussed the molecular functions and the clinical significances of KDM7C. PMID- 26816088 TI - Argentinean Society of Experimental Pharmacology: Brief history and main scientific contributions to the discipline. AB - Argentina Biomedical Science has been historically strong. The development of Human and Veterinary Pharmacology in our country as a pivotal discipline has been acknowledged worldwide because of the quality of its contributions. Argentinean Society of Experimental Pharmacology (SAFE) is a non- profit association whose research fields include Experimental and Clinical Pharmacology. SAFE main goals are described as follow (a) To meet active researchers for studying concerns regarding Experimental and Clinical Pharmacology (b) To launch an initiative for development of the discipline in mainly our country and other collaborative countries worldwide (c) To spread the pharmacological know-how obtained from different research teams (d) To strengthen relations between pharmacologists (e) To facilitate the presentation and discussion of scientific papers. This current article shows the SAFE's more important scientific contribution to pharmacology through its former research scientists to the present. PMID- 26816089 TI - Exploring patient- and physician-related factors preventing breast cancer patients from guideline-adherent adjuvant chemotherapy-results from the prospective multi-center study BRENDA II. AB - BACKGROUND: This study examined which patient- and physician-related factors influence guideline violations in adjuvant chemotherapy. PATIENTS AND METHODS: In a prospective multi-center cohort study, patients with primary breast cancer were sampled consecutively over a period of four years (2009-2012). Patients completed a questionnaire prior to surgery and prior to adjuvant therapy. This questionnaire assessed health-related quality of life (QoL) using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, psychiatric co morbidity with the Patient Health Questionnaire (PHQ), demographic characteristics (age, education), and the intensity of fear for chemotherapy. After surgery, a multi-professional team discussed recommendation for adjuvant chemotherapy, and this decision was documented in a database together with the indication for chemotherapy according to the German S3 guideline. This multi professional team was blinded to that algorithm-based decision. Six months later, it was documented whether the patient had received adjuvant chemotherapy or not. RESULTS: Altogether, 857 patients were included in the study. In 391 of these patients, the tumor board (TB) decided to recommend chemotherapy. The most important reasons for not recommending chemotherapy were somatic co-morbidity not allowing adjuvant chemotherapy and age >75 years. Of these 391 patients, 73 (19 %) patients eventually did not receive chemotherapy. Deviations from the initial therapy decision were more frequent in older patients (>=75 years) with poor QoL. If the QoL was good, higher age was not related to deviation. There was some evidence that patients with higher education less frequently received chemotherapy (CT). Furthermore, if patients were very afraid of chemotherapy, deviations from the initial therapy decision were more likely. Co-morbidity and fear of CT were not related to the likelihood of deviating from the initial therapy decision. CONCLUSION: Nineteen percent of patients eventually did not receive chemotherapy, despite guideline and TB recommendations. In these patients, this mainly occurred in association with poor QoL in elderly patients >75 years old. In the group with a chemotherapy recommendation, patients' fear of chemotherapy is another factor preventing patients from undergoing adjuvant chemotherapy. PMID- 26816090 TI - Detrimental social interactions predict loss of dignity among patients with cancer. AB - PURPOSE: This prospective study aimed to determine the extent to which cancer patients experience loss of dignity during primary cancer care (baseline) and at 3-month follow-up and the contribution of positive social support and detrimental social interactions on loss of dignity at follow-up. METHODS: At baseline, we enrolled N = 270 cancer patients (advanced cancer 57 %) undergoing oncological treatment. At follow-up, n = 178 patients (72 %) participated. Patients completed the following questionnaires: sense of dignity item (SDI), physical problem list of the NCCN Distress Thermometer, Illness-Specific Social Support Scale (SSUK), Patient Health Questionnaire (PHQ-9), and Generalized Anxiety Disorder Questionnaire (GAD-7). We conducted ordinal regression analyses controlling for age, gender, tumor stage, number of physical symptoms, depression, and anxiety. RESULTS: At baseline, 18 % of the patients experienced moderate to extreme loss of dignity (follow-up 23 %, p = 0.27). Detrimental interactions significantly predicted loss of dignity (OR = 1.42, 95 % CI 1.06-1.90) in a model including positive support (OR = 1.10, 95 % CI 0.82-1.49), depression (OR = 1.55, 95 % CI 0.96-2.51), and anxiety (OR = 1.20, 95 % CI 0.83-1.74). Items in relation to detrimental interactions with significant others such as "made you feel like you couldn't take care of yourself" (r = 0.29, p < 0.001) and "felt uncomfortable in illness conversations" (r = 0.24, p = 0.002) showed the highest associations with perceived loss of dignity. CONCLUSION: Loss of dignity was a frequent problem in our mixed cancer patient sample. Detrimental interactions that weaken the sense of dignity may result from discrepancies with patients' needs for autonomy and security. Tailoring social support to attachment-related patient needs may help to conserve patients' sense of dignity. PMID- 26816091 TI - Characteristics and outcome of unplanned hospital admissions in patients with lung cancer: a longitudinal tertiary center study. Towards a strategy to reduce the burden. AB - BACKGROUND: Unplanned hospital admissions (UHAs) are frequent in lung cancer, but literature on this topic is scarce. The aim of this study is to gain insight in the demographics, patterns of referral, causes, presenting symptoms, and final outcome of these UHAs. A strategy to improve quality of care and reduce the number and cost of UHAs was suggested based upon these findings. PATIENTS AND METHODS: In retrospective analysis of all consecutive UHAs in a 6-month period in a tertiary center, demographics, pattern of referral, clinical data, tumor control status, final diagnosis, duration of hospitalization, and outcome were examined. RESULTS: Two hundred seven UHAs were recorded. Male/female ratio was 185/62, mean age 65.5 years, performance status (PS) on admission 0-1 in 32 %, 2 in 37.2 %, and 3-4 in 30.8 % of patients. Patient referral occurred by general practitioner in 33.6 % or specialist in 25.5 % and in 40.9 % on own initiative. UHAs were therapy-related in 23.9 %, cancer-related in 47.4 %, comorbidity related in 19.4 %, or of unclear nature in 9.3 %. Most frequent causes were infections (21.9 %) and respiratory problems (17.0 %). Mean length of stay was 9.5 days. Final outcome was 10.1 % mortality, 6.9 % hospice care transfers, and 79.4 % home returns (including 18.2 % same day returns). CONCLUSION: UHAs in lung cancer were more cancer- than therapy-related. Majority of patients (2/3) were not seen by their general practitioner. A significant number of same day returns were noted. UHAs in patients with poor PS, uncontrolled cancer and cancer-related events had the worst outcome. This work is a first step in identifying specific characteristics of UHAs in lung cancer patients, which may lead to strategies to reduce the burden of UHAs. PMID- 26816093 TI - Metagenomes reveal microbial structures, functional potentials, and biofouling related genes in a membrane bioreactor. AB - Metagenomic sequencing was used to investigate the microbial structures, functional potentials, and biofouling-related genes in a membrane bioreactor (MBR). The results showed that the microbial community in the MBR was highly diverse. Notably, function analysis of the dominant genera indicated that common genes from different phylotypes were identified for important functional potentials with the observation of variation of abundances of genes in a certain taxon (e.g., Dechloromonas). Despite maintaining similar metabolic functional potentials with a parallel full-scale conventional activated sludge (CAS) system due to treating the identical wastewater, the MBR had more abundant nitrification related bacteria and coding genes of ammonia monooxygenase, which could well explain its excellent ammonia removal in the low-temperature period. Furthermore, according to quantification of the genes involved in exopolysaccharide and extracellular polymeric substance (EPS) protein metabolism, the MBR did not show a much different potential in producing EPS compared to the CAS system, and bacteria from the membrane biofilm had lower abundances of genes associated with EPS biosynthesis and transport compared to the activated sludge in the MBR. PMID- 26816092 TI - Microwave and ultrasound pre-treatments influence microbial community structure and digester performance in anaerobic digestion of waste activated sludge. AB - Comparative analyses of bacterial and archaeal community structures and dynamics in three biogas digesters during start-up and subsequent operation using microwaved, ultrasonicated or untreated waste activated sludge were performed based on 454 pyrosequencing datasets of part of 16S ribosomal RNA sequences and quantitative PCR. The pre-treatment increased the solubility, and thus the availability of the substrate for microbial degradation and significantly affected the succession of the anaerobic community structure over the course of the digestion. Bacteroidetes, Proteobacteria and Firmicutes were the dominant phyla in all digesters throughout operation. Proteobacteria decreased in relative abundance from 23-26 % to 11-13 % in association with enhanced substrate availability. Negative correlations between relative abundance of Alpha-, Beta- and Gammaproteobacteria and the substrate availability and/or biogas production were disclosed in statistical analyses. Clostridiales was the dominant order in Firmicutes, and Clostridiales, Clostridia and Firmicutes relative abundance and richness were shown to positively correlate with substrate availability and biogas generation. Methanogenic communities had a fairly restricted structure, highly dominated by Methanosaeta and Methanobrevibacter phylotypes. A gradual decline in Methanobrevibacter and increased representation of Methanosaeta concilii over time were particularly apparent in the digester receiving untreated waste activated sludge, whereas more diversified archaeal communities were maintained in the pre-treatment digesters. The quantitative PCR analyses revealed a methanogenic community distribution that coincided with the 454 pyrosequencing data. PMID- 26816094 TI - TAT-HSA-alpha-MSH fusion protein with extended half-life inhibits tumor necrosis factor-alpha in brain inflammation of mice. AB - Neuroinflammation constitutes a principal process involved in the progression of various central nervous system (CNS) disorders, including Parkinson's disease, Alzheimer's disease, ischemic stroke, and traumatic brain injury. The safety and efficacy of potential neuroprotective therapeutic agents is controversial and limited. Alpha-melanocyte-stimulating hormone (alpha-MSH) as a tridecapeptide derived from pro-opiomelanocortin displays potent anti-inflammatory and protective effects with a wide therapeutic window in brain damage. However, it is difficult to deliver effective concentrations of alpha-MSH into brain tissue via nondirect application. Besides, the half-life of the tridecapeptide is only a few minutes. In the present study, we generated a novel TAT-HSA-alpha-MSH by genetically fusing alpha-MSH with N-terminus 11-amino acid protein transduction domain of the human immunodeficiency virus Tat protein (TAT) and human serum albumin (HSA), which showed favorable pharmacokinetic properties and can effectively cross the blood brain barrier (BBB). The findings showed that TAT-HSA alpha-MSH significantly inhibits NF-kappaB activation in human glioma cells A172 and tumor necrosis factor-alpha (TNF-alpha) production in experimental brain inflammation. These results indicate that TAT-HSA-alpha-MSH may be a potential therapeutic agent for treating neuroinflammation which plays a fundamental role in CNS disorders. PMID- 26816095 TI - Lycopene Prevents Amyloid [Beta]-Induced Mitochondrial Oxidative Stress and Dysfunctions in Cultured Rat Cortical Neurons. AB - Brains affected by Alzheimer's disease (AD) show a large spectrum of mitochondrial alterations at both morphological and genetic level. The causal link between beta-amyloid (Abeta) and mitochondrial dysfunction has been established in cellular models of AD. We observed previously that lycopene, a member of the carotenoid family of phytochemicals, could counteract neuronal apoptosis and cell damage induced by Abeta and other neurotoxic substances, and that this neuroprotective action somehow involved the mitochondria. The present study aims to investigate the effects of lycopene on mitochondria in cultured rat cortical neurons exposed to Abeta. It was found that lycopene attenuated Abeta induced oxidative stress, as evidenced by the decreased intracellular reactive oxygen species generation and mitochondria-derived superoxide production. Additionally, lycopene ameliorated Abeta-induced mitochondrial morphological alteration, opening of the mitochondrial permeability transition pores and the consequent cytochrome c release. Lycopene also improved mitochondrial complex activities and restored ATP levels in Abeta-treated neuron. Furthermore, lycopene prevented mitochondrial DNA damages and improved the protein level of mitochondrial transcription factor A in mitochondria. Those results indicate that lycopene protects mitochondria against Abeta-induced damages, at least in part by inhibiting mitochondrial oxidative stress and improving mitochondrial function. These beneficial effects of lycopene may account for its protection against Abeta induced neurotoxicity. PMID- 26816097 TI - Opening Session/Keynote. PMID- 26816096 TI - Incorporation of an aggregation-induced-emissive tetraphenylethene derivative into cationic gene delivery vehicles manifested the nuclear translocation of uncomplexed DNA. AB - A fluorophore displaying aggregation-induced emission was introduced at the terminus of branched polyethylenimine (PEI). The formulated polyplex not only demonstrated an improved safety profile and preserved transfection activity but also importantly indicated that the uncomplexed naked DNA rather than the polyplexes translocated into the nucleus. PMID- 26816098 TI - Pre Congress Programs. AB - Imaging is increasingly being used by clinicians to enhance accuracy of diagnosis and to give important information regarding co-morbid pathologies which have an impact on management and prognosis. Imaging changes are increasingly entering clinical diagnostic criteria, and consensus clinical criteria for all main subtypes of dementia now include information about imaging changes. In addition, many clinical guidelines for dementia emphasize the need for informed, appropriate application of different imaging modalities in varying clinical situations. PMID- 26816099 TI - Plenaries. PMID- 26816100 TI - Free Communications. PMID- 26816101 TI - Symposia. PMID- 26816102 TI - Poster Presentations. PMID- 26816103 TI - Palladium-Catalyzed Synthesis of alpha-Iminonitriles from Aryl Halides via Isocyanide Double Insertion Reaction. AB - An efficient one-pot synthesis of alpha-iminonitriles from readily available aryl halides via palladium-catalyzed double isocyanide insertion and elimination has been developed, without using various hypertoxic cyanides and excess oxidants. Furthermore, the utility of this reaction was demonstrated by the rapid total synthesis of quinoxaline and the reaction of functional groups exchanged with aryl halides. PMID- 26816105 TI - Prognostic factors and long-term survival in surgically treated brain metastases from non-small cell lung cancer. AB - OBJECTIVE: Brain metastases (BMs) are the most common malignant brain tumors in adults. Despite multimodal treatment options such as microsurgery, radiotherapy and chemotherapy, prognosis still remains very poor. Non-small cell lung cancer (NSCLC) constitutes the most common source of brain metastases. In this study, prognostic factors in this patient population were identified through an in-depth analysis of clinical parameters of patients with BMs from NSCLC. PATIENTS AND METHODS: Clinical data of 114 NSCLC cancer patients who underwent surgery for BMs at the University Hospital Heidelberg were retrospectively reviewed for age, gender, type of treatment, time course of the disease, presence of neurologic symptoms, Karnofsky Performance Status (KPS), smoking history, presence of extracranial metastases at initial diagnosis of NSCLC, number, location and size of brain metastases. Univariate and multivariate survival analyses were performed using the Log-rank test and Cox' proportional hazard model, respectively. RESULTS: Median survival time from surgery for BMs was 11.2 months. 18.4% (21 of 114) patients were long-term survivors (>24 months; range 26.3-75.1 months). Age, gender, size and number of intracranial metastases were not significantly associated with patient survival. Univariate analysis identified complete resection, postoperative whole brain radiotherapy (WBRT) and a preoperative KPS of >80% as positive prognostic factors. Infratentorial location and presence of extracranial metastases were shown to be negative prognostic factors. Surgery for the primary tumor was associated with a superior patient outcome both in univariate and multivariate analyses. CONCLUSION: Our data strongly suggest that surgical treatment of the primary tumor and complete resection of brain metastases in NSCLC patients followed by WBRT improve survival. Moreover, long term survivors (>2 years) were more frequent than previously reported. PMID- 26816106 TI - Stereotactic fractionated radiotherapy of the resection cavity in patients with one to three brain metastases. AB - OBJECTIVES: The goal of this study is to evaluate the role of stereotactic fractionated radiotherapy (SFRT) in patients with one to three brain metastases after surgical resection. METHODS AND MATERIALS: We performed a retrospective single-institutional study in patients undergoing SFRT of surgical cavity after resection of <=3 brain metastases. 60 patients with newly diagnosed brain metastases treated with SFRT following resection were included. The total irradiation dose was 30 Gy (5 Gy/d, BED 45 Gy) after complete macroscopical resection and 35 Gy (5 Gy/d, BED 52.5 Gy) in patients with macroscopic residual tumour after surgery. Macroscopic residual tumour was defined as contrast enhancement next to the resection cavity on the postoperative T1-MRI. The gross tumour volume (GTV) encompassing the residual tumour was delineated on the T1 MRI, the clinical target volume (CTV) encompassed the surgical cavity plus 1mm and the planning target volume (PTV) the CTV plus 2mm. RESULTS: Eight of 60 patients had no imaging follow-up due to morbidity/mortality. Two of 52 (3.8%) patients experienced local failures only, 25 of 52 (48.1%) patients experienced distant intracranial failures only and 4 (7.7%) patients experienced both local and distant intracranial failures. In summary, there were 6 (11.5%) local failures and 29 (55.8%) distant failures. Age was significant for local control in the Cox regression test (p=0.046). Thirty-seven of 60 (61.7%) patients died during follow-up. Median follow-up was 8 months. Median overall survival was 15 months. Cox regression for survival was significant for KPS score <=70% and size of PTV. No severe side effects were seen. Patients undergoing whole brain radiation therapy (WBRT) as salvage therapy in case of progression had no severe side effects either. CONCLUSION: In the light of encouraging local control rates, SFRT could be an alternative to WBRT after surgical resection of <=3 brain metastases. Due to the high rate of distant intracranial failure regular follow up with MRI is mandatory. PMID- 26816107 TI - Tcstv1 and Tcstv3 elongate telomeres of mouse ES cells. AB - Mouse embryonic stem cell (ESC) cultures exhibit a heterogeneous mixture of metastable cells sporadically entering the 2-cell (2C)-embryo-like state, critical for ESC potency. One of 2-cell genes, Zscan4, has been shown to be responsible for telomere maintenance, genomic stability and pluripotency of mouse ESCs. Functions of other 2C-genes in ESCs remain elusive. Here we show that 2C genes Tcstv1 and Tcstv3 play a role in regulation of telomere lengths. Overexpression or knockdown Tcstv1 and Tcstv3 does not immediately affect proliferation, pluripotency and differentiation in vitro of ESCs. However, ectopic expression of Tcstv1 or Tcstv3 results in telomere elongation, whereas Tcstv1/3 knockdown shortens telomeres of ESCs. Overexpression of Tcstv1 or Tcstv3 does not alter telomere stability. Furthermore, Tcstv1 can increase Zscan4 protein levels and telomere recombination by telomere sister chromatid exchange (T-SCE). Depletion of Tcstv1/3 reduces Zscan4 protein levels. Together, Tcstv1 and Tcstv3 are involved in telomere maintenance that is required for long-term self-renewal of mouse ESCs. Our data also suggests that Tcstv1/3 may co-operate and stabilize Zscan4 protein but the molecular bases remain to be determined. PMID- 26816108 TI - Toward a better understanding of the oxaliplatin mode of action upon the steric hindrance of 1,2-diaminocyclohexane and its analogue. AB - The present research is concerned with the mechanism investigation on the interaction between oxaliplatin and guanosine 5'-monophosphate (GMP) in the presence of glutathione (GSH). The binding modes of oxaliplatin with GMP and GSH were explored by HPLC and LC-MS techniques, respectively, in which four key intermediates were found and five adducts were determined in the reaction. The results indicated that GSH can interfere with the reaction between oxaliplatin and DNA in two ways. One is by competing with GMP to bind the active platinum unit, and the other is by substituting the guanine-N7 atom of DNA to form inactive platinum species. In contrast to oxaliplatin with trans 1,2 diaminocyclohexane as spatial framework, a known platinum(II) complex, characteristic of trans-bicyclo[2.2.2]octane-7,8-diamine possessing dicyclic steric hindrance, was also studied in the same way to explore its mode of action with DNA. PMID- 26816109 TI - Catalytic reduction of dioxygen with modified Thermus thermophilus cytochrome c552. AB - Efficient catalysis of the oxygen reduction reaction (ORR) is of central importance to function in fuel cells. Metalloproteins, such as laccase (Cu) or cytochrome c oxidase (Cu/Fe-heme) carry out the 4H(+)/4e(-) reduction quite efficiently, but using large, complex protein frameworks. Smaller heme proteins also can carry out ORR, but less efficiently. To gain greater insight into features that promote efficient ORR, we expressed, characterized, and investigated the electrochemical behavior of six new mutants of cytochrome c552 from Thermus thermophilus: V49S/M69A, V49T/M69A, L29D/V49S/M69A, P27A/P28A/L29D/V49S/M69A, and P27A/P28A/L29D/V49T/M69A. Mutation to V49 causes only minor shifts to Fe(III/II) reduction potentials (E degrees '), but introduction of Ser provides a hydrogen bond donor that slightly enhances oxygen reduction activity. Mutation of L29 to D induces small shifts in heme optical spectra, but not to E degrees ' (within experimental error). Replacement of P27 and P28 with A in both positions induces a -50 mV shift in E degrees ', again with small changes to the optical spectra. Both the optical spectra and reduction potentials have signatures consistent with peroxidase enzymes. The V49S and V49T mutations have the largest impact of ORR catalysis, suggesting that increased electron density at the Fe site does not improve O2 reduction chemistry. PMID- 26816111 TI - Treatment Algorithms for Patients with Systemic Lupus Erythematosus: Comment on the Article by Muangchan et al. PMID- 26816112 TI - Tuberous sclerosis--A model for tumour growth. AB - Tuberous sclerosis complex (TSC) is a rare genetic disorder where patients develop benign tumours in several organ systems. Central to TSC pathology is hyper-activation of the mammalian target of rapamycin complex 1 (mTORC1) signalling pathway, which is a key controller of cell growth. As a result, TSC model systems are a valuable tool for examining mTORC1-driven cellular processes. The immunosuppressant, rapamycin, is a specific inhibitor of mTORC1 and has shown promise as a therapeutic agent in TSC as well as in malignancy. This review will focus on the cellular processes controlled by mTORC1 and how TSC-deficient cell lines and mouse models have broadened our understanding of the mTORC1 signalling network. It will also discuss how our knowledge of TSC signalling can help us understand sporadic conditions where mTORC1 activity is implicated in disease onset or progression, and the possibility of using rapamycin to treat sporadic disease. PMID- 26816113 TI - RNA binding proteins implicated in Xist-mediated chromosome silencing. AB - Chromosome silencing by Xist RNA occurs in two steps; localisation in cis within the nuclear matrix to form a domain that corresponds to the territory of the inactive X chromosome elect, and transduction of silencing signals from Xist RNA to the underlying chromatin. Key factors that mediate these processes have been identified in a series of recent studies that harnessed comprehensive proteomic or genetic screening strategies. In this review we discuss these findings in light of prior knowledge both of Xist-mediated silencing and known functions/properties of the novel factors. PMID- 26816114 TI - Hollow Microtube Resonators via Silicon Self-Assembly toward Subattogram Mass Sensing Applications. AB - Fluidic resonators with integrated microchannels (hollow resonators) are attractive for mass, density, and volume measurements of single micro/nanoparticles and cells, yet their widespread use is limited by the complexity of their fabrication. Here we report a simple and cost-effective approach for fabricating hollow microtube resonators. A prestructured silicon wafer is annealed at high temperature under a controlled atmosphere to form self assembled buried cavities. The interiors of these cavities are oxidized to produce thin oxide tubes, following which the surrounding silicon material is selectively etched away to suspend the oxide tubes. This simple three-step process easily produces hollow microtube resonators. We report another innovation in the capping glass wafer where we integrate fluidic access channels and getter materials along with residual gas suction channels. Combined together, only five photolithographic steps and one bonding step are required to fabricate vacuum packaged hollow microtube resonators that exhibit quality factors as high as ~ 13,000. We take one step further to explore additionally attractive features including the ability to tune the device responsivity, changing the resonator material, and scaling down the resonator size. The resonator wall thickness of ~ 120 nm and the channel hydraulic diameter of ~ 60 nm are demonstrated solely by conventional microfabrication approaches. The unique characteristics of this new fabrication process facilitate the widespread use of hollow microtube resonators, their translation between diverse research fields, and the production of commercially viable devices. PMID- 26816115 TI - A Model for the Active-Site Formation Process in DMSO Reductase Family Molybdenum Enzymes Involving Oxido-Alcoholato and Oxido-Thiolato Molybdenum(VI) Core Structures. AB - New bis(ene-1,2-dithiolato)-oxido-alcoholato molybdenum(VI) and -oxido-thiolato molybdenum(VI) anionic complexes, denoted as [Mo(VI)O(ER)L2](-) (E = O, S; L = dimethoxycarboxylate-1,2-ethylenedithiolate), were obtained from the reaction of the corresponding dioxido-molybdenum(VI) precursor complex with either an alcohol or a thiol in the presence of an organic acid (e.g., 10-camphorsulfonic acid) at low temperature. The [Mo(VI)O(ER)L2](-) complexes were isolated and characterized, and the structure of [Mo(VI)O(OEt)L2](-) was determined by X-ray crystallography. The Mo(VI) center in [Mo(VI)O(OEt)L2](-) exhibits a distorted octahedral geometry with the two ene-1,2-dithiolate ligands being symmetry inequivalent. The computed structure of [Mo(VI)O(SR)L2](-) is essentially identical to that of [Mo(VI)O(OR)L2](-). The electronic structures of the resulting molybdenum(VI) complexes were evaluated using electronic absorption spectroscopy and bonding calculations. The nature of the distorted O(h) geometry in these [Mo(VI)O(EEt)L2](-) complexes results in a lowest unoccupied molecular orbital wave function that possesses strong pi* interactions between the Mo(d(xy)) orbital and the cis S(p(z)) orbital localized on one sulfur donor from a single ene-1,2-dithiolate ligand. The presence of a covalent Mo-S(dithiolene) bonding interaction in these monooxido Mo(VI) compounds contributes to their low energy ligand-to-metal charge transfer transitions. A second important d-p pi bonding interaction derives from the ~180 degrees O(oxo)-Mo-E-C dihedral angle involving the alcoholate and thiolate donors, and this contributes to ancillary ligand contributions to the electronic structure of these species. The formation of [Mo(VI)O(OEt)L2](-) and [Mo(VI)O(SEt)L2](-) from the dioxidomolybdenum(VI) precursor may be regarded as a model for the active-site formation process that occurs in the dimethyl sulfoxide reductase family of pyranopterin molybdenum enzymes. PMID- 26816116 TI - [Rare form of transanal organ prolapse]. PMID- 26816117 TI - Iliac vessel injuries: difficult injuries and difficult management problems. AB - INTRODUCTION: Injury to the iliac vessels poses a serious and frustrating treatment dilemma for all trauma surgeons. Generally, patients present in profound shock secondary to severe hemorrhage from either iliac arterial, venous, or combined injuries. Despite improvements in our emergency medical services (EMS), rapid transport, standard training of trauma surgeons, and improved technology, the morbidity and mortality from iliac vessel injuries remain high, ranging from 25 to 40 %. MATERIALS AND METHODS: A systematic review of the literature, with emphasis placed on the diagnosis, treatment, and outcomes of these injuries, incorporating the author's experience. CONCLUSIONS: Injuries to the iliac vessel remain a daunting task, even after great advances in anatomic injury grading and damage control as well as advances in surgical techniques and critical care. Despite all the advances in treatment and appropriate management strategies, the morbidity and mortality from iliac vessel injuries remain high, demonstrating the complex challenge their treatment presents to even the modern day trauma surgeon. PMID- 26816118 TI - Femoral vessel injuries; high mortality and low morbidity injuries. AB - Femoral vessel injuries are amongst the most common vascular injuries admited in busy trauma centers. The evolution of violence and the increase in penetrating trauma from the urban battlefields of city streets has raised the incidence of femoral vessel injuries, which account for approximately 70% of all peripheral vascular injuries. Despite the relatively low mortality associated with these injuries, there is a high level of technical complexity required for the performance of these repairs. Similarly, they incur low mortality but are associated with significantly high morbidity. Prompt diagnosis and treatment are the keys to successful outcomes with the main goals of managing ischemia time, restoring limb perfusion, accomplishing limb salvage and instituting rehabilitation as soon as possible. PMID- 26816119 TI - Popliteal vessel injuries: complex anatomy, difficult problems and surgical challenges. AB - The incidence of popliteal vessel injuries is low, even in busy urban trauma centers. As a result of this fact, few trauma centers and trauma surgeons have developed extensive experience in the management of these injuries. Popliteal vessel injuries in both civilian and military arenas incur significant morbidity. These injuries present a difficult challenge, and, although the overall incidence of these injuries remains low, the sequelae can be devastating. Successful outcomes for limb salvage and survival result from early recognition and rapid surgical intervention by a multidisciplinary approach with a great participation of different surgical specialties. From the historical perspective, anatomy, incidence and associated injuries, to the clinical presentation, diagnosis, management, and morbidity and mortality, the aim of this article is to review the various aspects of these complex injuries. PMID- 26816120 TI - Shank vessel injuries: the forgotten vascular injuries. AB - INTRODUCTION: Vascular injuries in branch vessels of the popliteal artery, such as the tibioperoneal trunk, and shank vessels, such as anterior, posterior tibial, and peroneal vessels, occur in both blunt and penetrating trauma. Their management has evolved significantly in the past few decades. While their incidence is variable, limb loss and morbidity remain significant. MATERIAL AND METHODS: Physical examination, along with measuring an Ankle-Brachial Index (ABI), is still sometimes all that is required for diagnosis and can expeditiously triage those that require urgent operation. Despite our technological advancements and newer algorithms for lower extremity vascular trauma, operative intervention and exposure still remain difficult and pose a great challenge for surgeons that normally do not operate on this area. CONCLUSIONS: Shank vessel injuries still comprise a significant proportion of combat and civilian vascular injuries, and modern advances have led to a dramatic decrease in amputation rates. PMID- 26816121 TI - Quality of life after multiple trauma: validation and population norm of the Polytrauma Outcome (POLO) chart. AB - PURPOSE: Due to an increasing number of survivors after multiple injuries in Western countries, the health-related quality of life (QoL) is considered to be an important outcome parameter. Up to now, measuring instruments used in this field lacked validity and comparability. Within 6 years, our working group developed a new modular instrument, called the Polytrauma Outcome (POLO) chart. This study documents the validation of the trauma-specific module specifically designed for trauma patients, the Trauma Outcome Profile (TOP). METHODS: A total of 172 multiply injured patients (mean Injury Severity Score [ISS] 26.7) recruited from eight trauma centres participating in the German Trauma Registry were compared with 166 marginally injured patients (mean ISS 3.9). The mean follow-up was 24.2 and 26.4 months, respectively. The validation questionnaires used were the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), Impact of Event Scale-Revised (IES-R), Social Support Questionnaire (F SOZU-K-22), Barthel Index of Activities of Daily Living (ADL) and the Short Form Health Survey (SF-36). RESULTS: The internal consistency of the different dimensions of QoL assessed with the TOP was good. Factor analysis provides evidence of the construct validity of the questionnaire. Correlation with external measures gives evidence of criterion validity for the various dimensions of QoL and similar exceedance of proposed cut-off points within TOP and external measures is verified. CONCLUSION: The TOP module is a reliable and valid instrument to assess health-related QoL in patients with multiple injuries. It can be used stand-alone or as part of the POLO chart together with the Glasgow Outcome Scale (GOS), the EuroQoL and the SF-36 as a regular systematic follow-up instrument. PMID- 26816122 TI - Clinical re-evaluation of the relationship between gluteal injuries and embolized arteries in patients with massive hemorrhage following pelvic fracture. AB - PURPOSE: Transcatheter angiographic embolization (TAE) has been widely accepted as a treatment for hemorrhagic shock associated with pelvic fracture. Gluteal muscle necrosis is a rare but potentially fatal complication of TAE. This study aimed to clarify factors associated with safer embolization procedures by evaluating relationships between embolic site and risk of gluteal skin injury. METHODS: We classified embolized arteries into six groups: group A, nonselective embolization from the main internal iliac artery; group B, selective embolization including the superior gluteal artery but excluding the inferior gluteal artery; group C, selective embolization including the inferior gluteal artery but excluding the superior gluteal artery; group D, selective embolization including both the superior and inferior gluteal arteries; group E, selective embolization excluding both the superior and inferior gluteal arteries; and group F, no embolization. We assessed the frequency of gluteal injuries, relationships between gluteal injuries and embolized arteries, and the contributions of selective embolization, conservation of the superior or inferior gluteal artery, and conservation of both the superior and inferior gluteal arteries to reducing the risk of gluteal injury. RESULTS: Gluteal skin injuries were seen at 15 of 160 sites (9.4%). A significant difference was noted between the nonselective embolization group (group A: 10/82, 12.2%) and selective embolization excluding both the superior and inferior gluteal arteries (group E: 1/39, 2.6%) (p = 0.042). CONCLUSIONS: If possible, we recommend selective embolization avoiding the superior and inferior gluteal arteries. PMID- 26816123 TI - Early access to rehabilitation for paediatric patients with traumatic brain injury. AB - INTRODUCTION: Paediatric major trauma centres are being developed in the UK. As a paediatric unit within a large regional hospital that is co-located with a neurosciences centre, we conducted this study to establish what inpatient rehabilitation service is offered to patients with traumatic brain injury (TBI). It is known that early rehabilitation improves prognosis. MATERIALS AND METHODS: A retrospective review of all patients under the age of 16 years admitted with an ICD-10 diagnosis of head injury was conducted. We collected data on the presentation, interventions, rehabilitation and follow up arrangements of this patient cohort. RESULTS: A total of 146 patients were identified, of whom >50% had a traumatic lesion on brain computed tomography (CT) identified and 18% had a new diagnosis related to their TBI at discharge. 56% of patients with severe head injury were assessed by a neurodisability team member, but this dropped to 15% for the moderate cases and 5% for the mild cases. CONCLUSIONS: Many children who were admitted with TBI did not have access to early rehabilitation. PMID- 26816124 TI - Correlation of operative and pathological injury grade with computed tomographic grade in the failed nonoperative management of blunt splenic trauma. AB - BACKGROUND: Computed tomography (CT) is the standard for grading blunt splenic injuries, but the true accuracy, especially for grade IV or V injuries as compared to pathological findings, is unknown. STUDY DESIGN: A retrospective study from 2005 to 2011 was undertaken. RESULTS: There were 214 adults admitted with blunt splenic injury and 170 (79%) were managed nonoperatively. The remaining 44 patients (21%) required surgical intervention. There was a significant difference in the Injury Severity Score (ISS) between those who did and those who did not require splenectomy: median 31 (interquartile [IQ] range 11 51) versus 22 (IQ range 9-35, p = 0.0002). Ten patients presented in shock, had a positive ultrasound, and went to surgery. The remaining 34 had CT scans prior to surgery. Twenty-five (73%) had injury grades IV or V. The CT scan correctly graded the injury in 14 (41%) and was incorrect in 20 (59%). The assigned grade by the CT scan underestimated the true injury grade by one grade in six cases (30%), by two or more grades in nine (45%), and the CT images were obscured by blood and deemed "ungradeable" in five (25%). The CT scan was more accurate for grades I and II (100%) than for grades III-V (25-43%). The reasons for inaccuracy were either inability to visualize that the laceration involved the hilar vessels or excessive perisplenic blood which obscured the injury and/or the hilum. CONCLUSIONS: CT for splenic injury is accurate for grades I and II, but underestimates the true extent of injury for grades III-V. The reasons for the lack of correlation are the inability to determine hilar involvement and excessive perisplenic blood obscuring the injury. Patients with these image characteristics by CT scan should undergo splenectomy earlier if there are any signs of hemodynamic instability. PMID- 26816125 TI - Pelvic circumferential compression devices (PCCDs): a best evidence equipment review. AB - PURPOSE: Traumatic disruption of the pelvis can lead to significant morbidity and mortality. ATLS((r)) guidance advocates temporary stabilisation or 'closure' of the disrupted pelvis with a compression device or sheet. We undertook a best evidence equipment review to assess the ease and efficacy of the application of two leading commercially available devices, the T-POD((r)) and the SAM Pelvic SlingTM II. METHODS: Fifty health care professionals and medical students participated in pelvic circumferential compression device (PCCD) education and assessment. Participants received a 10-min lecture on the epidemiology and aetiology of pelvic fractures and the principles of circumferential compression, followed by a practical demonstration. Three volunteers acted as trauma victims. Assessment included the time taken to secure the devices and whether this was achieved correctly. All participants completed a post-assessment survey. RESULTS: Both devices were applied correctly 100% of the time. The average time taken to secure the SAM Pelvic SlingTM II was 18 s and for the T-POD((r)), it was 31 s (p <= 0.0001). Forty-four participants (88%) agreed or strongly agreed that the SAM Pelvic SlingTM II was easy to use compared to 84% (n = 42) for the T-POD((r)). Thirty-nine participants (78%) reported that they preferred and, given the choice in the future, would select the T-POD((r)) over the SAM Pelvic SlingTM II (n = 11, 22%). CONCLUSIONS: The results of this study indicate that both PCCDs are easy and acceptable to use and, once learned, can be applied easily and rapidly. Participants applied both devices correctly 100% of the time, with successful application taking, on average, less than 60 s. PMID- 26816126 TI - A comparative study between gamma nail and percutaneous compression plating for the treatment of intertrochanteric hip fractures. AB - PURPOSE: Nowadays, the literature shows better results in the treatment of intertrochanteric (AO/OTA 31.A1-A2) hip fractures with dynamic hip screw (DHS) compared with gamma nail (GN). Besides, percutaneous compression plate (PCCP) gives results which are better or similar to those obtained with DHS. But only two reports compare the results between PCCP and GN. The aim of this trial is to compare the outcome of treatment of these fractures with either a PCCP or a GN. METHODS: A retrospective trial with 414 patients over 60 years of age treated in our institution for 6 years, with a minimum follow-up of 1 year, was performed to compare the outcome of a PCCP (240) with a GN (174). RESULTS: The post-operative hospital stay was 2 days longer in the GN group compared to the PCCP group (p < 0.001). The post-operative haemoglobin serum level was slightly lower in the GN group (relative risk (RR) -0.28, 95% confidence interval (CI): -0.02 to -0.54, p = 0.036) and the transfusion requirement was lower in the PCCP group (GN 53.4% vs. PCCP 33.8%, p < 0.001). The procedure-related complications rate was higher in the GN group (9.8 vs. 5%, p = 0.06). CONCLUSIONS: PCCP has lower overall economical cost and blood transfusional requirements for a similar or better outcome in terms of procedure-related complications. PMID- 26816127 TI - Chronic pain and its impact on quality of life following a traumatic rib fracture. AB - PURPOSE: Traumatic rib fractures account for 7-40 % of trauma admissions and most of them heal spontaneously and do not contribute to disability. The prevalence of chronic pain and its impact on quality of life following a traumatic rib fracture has not been studied adequately. METHODS: A retrospective review of electronic medical records of all the traumatic rib fracture admissions from January 2007 to December 2008 was conducted. This was followed up with a brief telephonic survey of the following questions: (1) Do you have pain following the trauma? (2) If YES, how severe is your pain from a score of zero to ten? (3) Does the pain affect your life style? (4) Does the pain affect your work? (5) Do you need to take regular pain medications? RESULTS: One hundred and two patients responded to the survey and 23 patients (22.5 %) complained of chronic persistent pain. In patients with pain, six patients (26 %) had chronic pain that required regular use of analgesics, eight patients (35 %) complained of impairment of work life, and three patients (13 %) complained of impairment of personal quality of life. Chronic pain was not related to age, number of ribs fractured, flail chest, hemothorax and/or pneumothorax, chest tube insertion, or Injury Severity Score (ISS). CONCLUSION: This study confirms the high incidence of chronic pain after a traumatic rib fracture. While the majority of the patients can manage this pain without interference of their quality of life, a few do suffer from life style/work interference and may have to resort to regular analgesic usage. PMID- 26816128 TI - Characteristics of bone metabolism markers during the healing of osteoporotic versus nonosteoporotic metaphyseal long bone fractures: a matched pair analysis. AB - PURPOSE: The activity and metabolism of fracture healing can be monitored quantitatively by measuring bone turnover markers (BTMs) in serum or urine. However, in osteoporotic bone, the exact metabolism processes during the healing of metaphyseal fractures remain unknown. There is no diagnostic approach which currently allows dynamic insight into the fracture healing processes in order to monitor the progression of healing and to assist in therapeutic decision making. METHODS: Between March 2007 and February 2009, 30 patients over 50 years of age who suffered a metaphyseal fracture were included in our study. The levels of the osteoanabolic marker BAP (bone-specific alkaline phosphatase) and osteocatabolic marker beta-CTX [crosslinked C-(CTX)-telopeptide-of-type-I-collagen] were monitored during the fracture healing of osteoporotic and nonosteoporotic fractures for a duration of 8 weeks. RESULTS: After an initial decrease of BAP in the first week, the BAP level steadily increased through the fourth week in both groups. The levels of BAP in the osteoporotic group surpassed the healthy group. beta-CTX steadily increased in healthy bone up to the fourth week; in osteoporotic bone, beta-CTX first increased and, thereafter, decreased from the first week onwards. CONCLUSIONS: In this work, the first molecular biological aspects of osteoporotic fracture healing have been uncovered, helping to explain the mechanisms of delayed fracture healing in osteoporotic bone. The early decrease of reduced beta-CTX as well as elevated BAP during the healing process may be the first aspects within the delayed healing of osteoporotic bone. Further studies are necessary in order to achieve more detailed insight to fracture healing and to ascertain the progression of fracture healing as being essential (criteria) for therapeutic decision making. PMID- 26816129 TI - Sigmoid volvulus treated by resection and primary anastomosis: urgent and elective conditions as risk factors for postoperative morbidity and mortality. AB - PURPOSE: Sigmoid volvulus is a major cause of intestinal obstruction. The aim of this study is to analyze urgent and elective conditions as risk factors for morbidity and mortality regarding sigmoid colon resection and primary anastomosis in patients with sigmoid volvulus. METHODS: This retrospective study included 63 patients diagnosed with sigmoid volvulus, who underwent sigmoid colon resection plus primary anastomosis under urgent or elective conditions between January 1994 and December 2010. RESULTS: Sigmoid colon resection plus anastomosis was performed in 63 patients; 31 (49.2 %) under urgent conditions, while 32 (50.8 %) were performed electively. The mean age of the patients was 65.2 +/- 15.2 (18-95) years. The patients consisted of 50 (79.4 %) men and 13 (20.6 %) women. There were no statistical significances between groups in terms of age, gender, associated diseases, and hospital stay. Postoperative morbidity occurred in 30.2 % of patients. The morbidity rates for the urgent group and the elective group were 35.5 and 25.0 %, respectively (p = 0.419). Wound infection, pneumonia, and evisceration were the most common postoperative complications. Wound infection was higher in the urgent group (p = 0.026). In terms of other complications, the groups were similar. Total mortality occurred in 19.4 % of the urgent group and 15.6 % of the elective group (p = 0.750). CONCLUSION: Sigmoid colon resection plus primary anastomosis-related morbidity and mortality rates were similar in patients who were operated on under urgent and elective conditions, and who maintained good general condition. PMID- 26816131 TI - Message from the president. PMID- 26816130 TI - Low incidence of penetrating trauma in a high-volume tertiary center: 10-year mortality review. AB - BACKGROUND: Trauma morbidity and mortality outcome is better in high-volume trauma centers. However, there are few publications investigating the experience of high-volume centers with high non-trauma emergency load but seeing a relatively low incidence of trauma. The objective of this study is to review the presentation and outcomes for the low volume of patients presenting with penetrating injuries in a high-volume hospital. METHODS: Data were extracted from the Singapore General Hospital database between 1998 and 2007. There were 1,233 patients who sustained penetrating injuries and were brought to the hospital during the 10-year period. Of these, only 78 patients had injury severity score (ISS) values of 16 or more. In the same period, there were 1,270 patients with ISS > 15 who were admitted with blunt injury. SPSS 10.1 was used to conduct univariate and multivariate analyses to elucidate risk factors for mortality. RESULTS: Age, ISS, and trauma injury severity score (TRISS) were significant predictors of mortality. Gender and type of injury were not predictive of mortality. Mortality outcomes were independently predicted by age, TRISS, and ISS. The most common site of injury was the chest, followed closely by the head and neck. The abdomen/pelvis was the third most common site of injury. There was no significant difference in anatomical site injury pattern between the survivors and non-survivors. For both groups, chest injuries and head and neck injuries dominated, with maximal abdominal/pelvic injuries a distant third. CONCLUSION: With a trauma system in place, high-volume centers with a low volume of penetrating injury patients can still manage uncommon injuries without jeopardizing patient care. PMID- 26816132 TI - Deconstructing a Species-Complex: Geometric Morphometric and Molecular Analyses Define Species in the Western Rattlesnake (Crotalus viridis). AB - Morphological data are a conduit for the recognition and description of species, and their acquisition has recently been broadened by geometric morphometric (GM) approaches that co-join the collection of digital data with exploratory 'big data' analytics. We employed this approach to dissect the Western Rattlesnake (Crotalus viridis) species-complex in North America, currently partitioned by mitochondrial (mt)DNA analyses into eastern and western lineages (two and seven subspecies, respectively). The GM data (i.e., 33 dorsal and 50 lateral head landmarks) were gleaned from 2,824 individuals located in 10 museum collections. We also downloaded and concatenated sequences for six mtDNA genes from the NCBI GenBank database. GM analyses revealed significant head shape differences attributable to size and subspecies-designation (but not their interactions). Pairwise shape distances among subspecies were significantly greater than those derived from ancestral character states via squared-change parsimony, with the greatest differences separating those most closely related. This, in turn, suggests the potential for historic character displacement as a diversifying force in the complex. All subspecies, save one, were significantly differentiated in a Bayesian discriminant function analysis (DFA), regardless of whether our priors were uniform or informative (i.e., mtDNA data). Finally, shape differences among sister-clades were significantly greater than expected by chance alone under a Brownian model of evolution, promoting the hypothesis that selection rather than drift was the driving force in the evolution of the complex. Lastly, we combine head shape and mtDNA data so as to derived an integrative taxonomy that produced robust boundaries for six OTUs (operational taxonomic units) of the C. viridis complex. We suggest these boundaries are concomitant with species status and subsequently provide a relevant nomenclature for its recognition and representation. PMID- 26816133 TI - Face perception in schizophrenia: a specific deficit. AB - INTRODUCTION: Patients with schizophrenia have a large-scaled and severe cognitive impairment. This study examines whether a well-established deficit in face recognition in schizophrenia is a part of this general cognitive impairment or is specific to faces per se. METHOD: The differential deficit in matching upright faces as compared with two psychometrically matched control tasks (matching inverted faces and matching none-face objects) was assessed in two well matched samples of schizophrenics (n = 40) and controls (n = 40). RESULTS: Indicating a generalised cognitive deficit, schizophrenics were impaired in all tasks. Importantly, however, the deficit in matching upright faces was stronger in magnitude (15.6%) than the deficits in matching inverted faces (10.1%) and non face objects (10.2%). Consistently, schizophrenics showed weaker face inversion effects, indicating a configural processing dysfunction. CONCLUSION: These results provide compelling evidence for a face-specific deficit in schizophrenia that may be associated with, but separable from, a generalised cognitive impairment. PMID- 26816135 TI - Childhood and Youth Onset Diabetes: A Single Centre Experience. AB - OBJECTIVES: To identify proportion of various types of diabetes and differences between type 1 and type 2 diabetes in patients with youth onset diabetes (onset below 25 completed years of age). In addition, concurrent autoimmune diseases in type 1 diabetes were studied in a subset of patients. METHODS: A total of 577 patients (192 girls) with diabetes onset at median age of 14 y (range 1 mo-25 y) with median duration of 1 y (range day of diagnosis- 43 y) were included. Clinical details, investigations and complications were recorded in a proforma. Diabetes was classified using clinical criteria supported by laboratory tests of C peptide and anti GAD-65 antibody in a subset of patients. RESULTS: Type 1 diabetes accounted for 368/421 (87.4 %) patients with age of onset <18 y and 99/156 (63.5 %) of patients with onset between 19 and 25 y of age. Proportion of type 2 diabetes was 36/421 (8.5 %) and 41/156 (26.2 %) in these two groups. Older age at onset, diabetes in one or both parents, absence of ketosis /weight loss and presence of acanthosis were significant predictors of type 2 diabetes. Hypothyroidism (TSH >10) and biopsy proven celiac disease was found in 11.6 and 9.7 % of type 1 diabetes patients respectively. CONCLUSIONS: Type 1 diabetes is the most common type of diabetes in youth, however, a significant proportion of youth have type 2 diabetes. In these patients a combination of clinical factors, biochemical parameters and course over few months helps to guide the diagnosis. PMID- 26816136 TI - Myths About Private Cord Blood Banking. PMID- 26816138 TI - Mechanism and Thermodynamics of Reductive Cleavage of Carbon-Halogen Bonds in the Polybrominated Aliphatic Electrophiles. AB - Quantum-mechanical computations revealed that, despite the presence of electron withdrawing and/or pi-acceptor substituents, the lowest unoccupied molecular orbitals (LUMO) of the polybromosubstituted aliphatic molecules R-Br (R-Br = C3Br2F6, CBr3NO2, CBr3CN, CBr3CONH2, CBr3CO2H, CHBr3, CFBr3, CBr4, CBr3COCBr3) are delocalized mostly over their bromine-containing fragments. The singly occupied molecular orbitals in the corresponding vertically excited anion radicals (R-Br(*-))* are characterized by essentially the same shapes and show nodes in the middle of the C-Br bonds. An injection of an electron into the antibonding LUMO results in the barrierless dissociation of the anion-radical species and the concerted reductive cleavages of C-Br bonds leading to the formation of the loosely bonded {R(*)...Br(-)} associates. The interaction energies between the fragments of these ion-radical pairs vary from ~10 to 20 kcal mol(-1) in the gas phase and from 1 to 3 kcal mol(-1) in acetonitrile. In accord with the concerted mechanism of reductive cleavage, all R-Br molecules showed completely irreversible reduction waves in the voltammograms in the whole range of the scan rates employed (from 0.05 to 5 V s(-1)). Also, the transfer coefficients alpha, established from the width of these waves and dependence of reduction peak potentials Ep on the scan rates, were significantly lower than 0.5. The standard reduction potentials of the R-Br electrophiles, E(o)R-Br/R.+X( ), and the corresponding R(*) radicals, E(o)R(*)/R(-), were calculated in acetonitrile using the appropriate thermodynamic cycles. In agreement with these calculations, which indicated that the R(*) radicals resulting from the reductive cleavage of the R-Br molecules are stronger oxidants than their parents, the reduction peaks' currents in cyclic voltammograms were consistent with the two electron transfer processes. PMID- 26816137 TI - Serum Basic Fibroblastic Growth Factor Levels in Children with Infantile Hemangioma. AB - OBJECTIVES: To determine serum levels of basic fibroblastic growth factor (b-FGF) in hemangioma patients under 2 y of age. METHODS: The study group consisted of 43 children with infantile hemangioma and b-FGF levels were analyzed using ELISA. RESULTS: The serum b-FGF levels were higher in hemangioma patients than in healthy control individuals (p 0.01). There were no differences between the lesion size, number of lesions, patient age and serum b-FGF levels. CONCLUSIONS: Thus, b-FGF is an important growth factor that plays a central role in hemangioma, but determining b-FGF serum levels was not helpful in distinguishing between patients who require treatment and those who do not. PMID- 26816139 TI - Micropore extrusion-induced alignment transition from perpendicular to parallel of cylindrical domains in block copolymers. AB - The orientation transition from perpendicular to parallel alignment of PEO cylindrical domains of PEO-b-PMA(Az) films has been demonstrated by extruding the block copolymer (BCP) solutions through a micropore of a plastic gastight syringe. The parallelized orientation of PEO domains induced by this micropore extrusion can be recovered to perpendicular alignment via ultrasonication of the extruded BCP solutions and subsequent annealing. A plausible mechanism is proposed in this study. The BCP films can be used as templates to prepare nanowire arrays with controlled layers, which has enormous potential application in the field of integrated circuits. PMID- 26816141 TI - Focus On Intramedullary Nailing. PMID- 26816140 TI - In vitro stereospecific hydration activities of the 3-vinyl group of chlorophyll derivatives by BchF and BchV enzymes involved in bacteriochlorophyll c biosynthesis of green sulfur bacteria. AB - The photosynthetic green sulfur bacterium Chlorobaculum (Cba.) tepidum produces bacteriochlorophyll (BChl) c pigments bearing a chiral 1-hydroxyethyl group at the 3-position, which self-aggregate to construct main light-harvesting antenna complexes, chlorosomes. The secondary alcoholic hydroxy group is requisite for chlorosomal aggregation and biosynthesized by hydrating the 3-vinyl group of their precursors. Using recombinant proteins of Cba. tepidum BchF and BchV, we examined in vitro enzymatic hydration of some 3-vinyl-chlorophyll derivatives. Both the enzymes catalyzed stereoselective hydration of zinc 3-vinyl-8-ethyl-12 methyl-bacteriopheophorbide c or d to the zinc 31 R-bacteriopheophorbide c or d homolog, respectively, with a slight amount of the 31 S-epimric species. A similar R-stereoselectivity was observed in the BchF-hydration of zinc 3-vinyl-8 ethyl- and propyl-12-ethyl-bacteriopheophorbides c, while their BchV-hydration gave a relatively larger amount of the 31 S-epimers. The in vitro stereoselective hydration confirmed the in vivo production of the S-epimeric species by BchV. The enzymatic hydration for the above 8-propylated substrate proceeded more slowly than that for the 8-ethylated, and the 8-isobutylated substrate was no longer hydrated. Based on these results, biosynthetic pathways of BChl c homologs and epimers are proposed. PMID- 26816142 TI - Current Concepts: Aseptic Nonunion of Femoral Shaft Diaphysis. AB - In spite of increased understanding of biomechanics and improvements of implant design, nonunion of femoral shaft fractures continues to hinder the treatment of these injuries. Femoral nonunion presents a difficult treatment challenge for the surgeon and a formidable personal and economic hardship for the patient. In most series of femoral fractures treated with intramedullary nailing techniques, the incidence of this complication is estimated to be 1%. A higher frequency has recently been reported due to advances in trauma care leading to increased survivorship among severely injured patients and expanded indications of intramedullary nailing. Whereas the treatment of femoral shaft fractures has been extensively described in the orthopedic literature, the data regarding treatment of femoral shaft nonunions are sparse and conflicting, as most of the reported series consisted of a small number of cases. However, careful review of the existing literature does provide some answers regarding either conservative or operative management. The gold standard for femoral shaft nonunions invariably includes surgical intervention in the form of closed reamed intramedullary nailing or exchange nailing, but several alternative methods have been reported including electromagnetic fields, low-intensity ultrasound, extracorporeal shock wave therapy, external fixators and exchange or indirect plate osteosynthesis. In this paper, a comprehensive review of the current treatment modalities for aseptic midshaft femoral nonunion is presented, after a concise overview of the incidence, definition, classification and risk factors of this complication. PMID- 26816143 TI - Antegrade Versus Retrograde Locked Intramedullary Nailing for Femoral Fractures: Which Is Better? AB - BACKGROUND: Locked intramedullary nailing or interlocking nailing (ILN) is a proven mode of treatment for femoral shaft fractures. It can be inserted via the antegrade or retrograde approach. Retrograde approach is technically less demanding especially if the patient is overweight. But there are concerns with regard to the violation of the knee and its effect on subsequent knee function. METHODS: We studied consecutive cases of femoral shaft fractures treated with locked intramedullary nailing at the Penang General Hospital, from 1st June 2004 to 1st June 2005. We looked at radiological and clinical union rates, union of fractures, alignment of the operated limb, and the knee function, using the Thoresen scoring system. RESULTS: There were a total of 77 cases of femoral interlocking nails during the study period. Forty-two cases were antegrade nails and 35 cases were retrograde nails. Both groups of patients eventually achieved union of the fracture and retrograde nailing group showed significantly earlier union rate (p = 0.032). There is no significant difference between both groups, in regards to knee pain, swelling, and range of motion as well as postnailing femoral alignment. CONCLUSIONS: Both methods of nailing achieved excellent union rates with good alignment of the limb. Contrary to popular belief, we found that retrograde nailing does not give rise to a higher rate of knee complications. Therefore, we strongly recommend this approach of nailing as it is technically less demanding. PMID- 26816144 TI - Intramedullary Stabilization of Proximal Femoral Fractures. AB - For nearly 40 years, extramedullary stabilization using the sliding hip screw and plate has been the standard fixation method for proximal femoral fractures. In patients with stable fractures, this device produces excellent results. However, in patients with unstable fractures, the sliding hip screw and plate is associated with an increased prevalence of complications, particularly cut-out, medialization of the shaft, shortening, and subsequent loss of reduction. For these reasons, there has been a sustained interest in the use of an intramedullary nail to treat proximal femoral fractures. However, intramedullary methods of therapy for trochanteric fractures require extensive operative experience. The incidence of complications, e.g. cut-out, femoral shaft fractures, and the learning curve has resulted in a loss off popularity of these devices in the past. The aim of this overview is to analyze and record the current standards by means of recent papers and to present the experience after intramedullary stabilization of more than 3,000 patients with proximal femoral fractures at our level I trauma center. PMID- 26816145 TI - Intramedullary Nailing of Humeral Head and Humeral Shaft Fractures. AB - There is an increasing interest in intramedullary nailing for humeral fractures. Starting with diaphyseal fractures, now also proximal metaphyseal fractures of the humerus can be nailed with satisfying results. Basic ideas for humeral nailing are less invasive approaches to the humerus, less soft tissue damage, e.g. lower rates of radial nerve palsy, closed reduction and the biomechanical aspects of a central implant with elastic fixation properties. Nailing of diaphyseal humeral shaft fractures is an equivalent alternative to plating; nailing of proximal metaphyseal humeral fractures is still new and needs more reliable scientific data to clear its advantages compared to other fixation techniques. Nailing of distal metaphyseal humeral fractures is no serious option at the moment. Angular stable interlocking systems show better fixation qualities for proximal fractures or fracture components. Although in very osteoporotic bone cutouts are registered. Static interlocking is advisable. High torsional stability of the fracture fixation has to be achieved, since significant torsional load occurs during the usual movement of the upper limbs. As there is an important learning curve, possible complications of intramedullary nailing have to be kept in mind and avoided by a careful operation technique. PMID- 26816146 TI - Extending the Indication of Intramedullary Nailing of Tibial Fractures. AB - Intramedullary nailing is an effective and well-established method for the treatment of a wide spectrum of tibial fractures. Nevertheless, the handling of metaphyseal and open fracture remains challenging. Surgical and technical advancements have opened up new possibilities to broaden the indication of intramedullary nailing in these areas. PMID- 26816147 TI - Pelvic Ring Fractures: Utility of Clinical Examination in Patients with Impaired Consciousness or Tracheal Intubation. AB - OBJECTIVE: To define the diagnostic accuracy of clinical examination in patients with impaired consciousness or endotracheal intubation to detect pelvic ring fractures and to identify those with severe bleeding. METHODS: Included in this prospective data collection with retrolective data analysis were a consecutive series of blunt trauma victims with either a Glasgow Coma Scale <= 13 or tracheal intubation. Clinical examination comprised testing for stability of the iliac wings. RESULTS: From 784 subjects (injury severity score 23.3 +/- 17.4) 93 patients (11.9%) were found to have a pelvic ring fracture. Clinical instability of the pelvic ring was found in 42 patients. There was only one false positive. Fifty-two fractures could not be identified by clinical examination, including nine fractures (17%) that required surgical fracture stabilization (sensitivity of clinical examination 44.1%). Seventeen fractures (18.3%) were associated with a blood loss larger than 20% of circulating blood volume. Sixteen of those were identified by clinical instability of the pelvic ring (sensitivity 94.1%, specificity 97.0%, positive predictive value 38.1%, negative predictive value 99.9%). CONCLUSIONS: Clinical examination for stability of the pelvis in this selected group of patients missed a significant number of pelvic ring fractures including fractures that require surgical stabilization. The finding of a clinically unstable identifies most of the patients with the pelvic ring fracture being a major source of bleeding. A stable pelvis makes pelvic ring fracture as being the source of bleeding quite unlikely. PMID- 26816148 TI - Interhospital Transportation of Mass Burn Casualties. AB - AIM OF STUDY: To establish the impact of the transportation on the condition and outcome of the victims of the Volendam fire incident. METHODS: Medical and logistic parameters from all victims in the Intensive Care Unit (ICU) were retrospectively collected. Physiologic parameters in the first 24 h and outcome parameters were compared between the transported and the non-transported patients. RESULTS: The first 24 h, 105 patients were admitted to an ICU: 47 of them were relocated during that same day. The pH value was significantly lower in the transported group (p = 0.016). Systolic blood pressure, bicarbonate, carbon dioxide, temperature, APACHE II score and fluctuation during the first day, as well as condition during the second day did not differ significantly. The origin of the acidosis seemed to be mainly metabolic. The number of hospitalization days was larger in the transported group with severe burn injury (>=25% total body surface area burnt), comparing to the non-transported group (p = 0.015). Ventilation days and mortality did not differ significantly. CONCLUSIONS: The transported patients had a lower pH the first day after transportation, but condition during the second day as well as ventilation day and mortality did not differ between the transported and the non-transported group. Therefore, transportation during the unstable phase, the first day post-burn, seemed not to have had a negative impact on patient outcome. PMID- 26816149 TI - Towards Regionalized Care of Severe Orthopedic Injuries: A Survey on Non university Hospitals in Finland. AB - INTRODUCTION: The principles of a designated trauma system and regionalization of trauma care exist in very limited areas in Finland. In this study, we obtained information on the current personal opinions of orthopedicsin-chief (OICs) and surgeons-in-chief (SICs) towards regionalization of severe orthopedic trauma care in Finland. MATERIALS AND METHODS: A questionnaire was sent to OICs and SICs working in 36 primary and secondary hospitals providing acute surgical care asking to give their personal opinions whether certain severe orthopedic injuries should be managed in their hospitals or be referred. RESULTS: The overall response rate was 49/67 (73%). In general, SICs tended to be more reluctant to refer patients to higher level facilities. Both OICs and SICs were more willing to refer spinal and pelvic injuries than complicated long bone fractures. CONCLUSIONS: There seems to be major differences in personal views on referral policy between OICs and SICs. This information is useful prior to discussions by the professional organizations, hospitals, and the government in establishing a modern orthopedic trauma system in Finland. PMID- 26816150 TI - Acute Gluteal and Thigh Compartment Syndrome following Pelvic Fracture and Superior Gluteal Artery Bleed : A Case Report and Review of the Literature. AB - Injury to the superior gluteal artery as a result of pelvic fracture is well recognized. Superior gluteal artery bleed leading to gluteal compartment syndrome without fracture of the pelvis has been reported but is extremely rare. Similarly, acute compartment syndrome of the thigh is rare. As far as is known, no previous case has been reported where a combination of pelvic fracture and superior gluteal artery bleed has led to acute gluteal and thigh compartment syndrome. We report on such a patient who developed these complications and highlight the importance of early detection, which may be difficult in an unconscious or comatose patient. PMID- 26816151 TI - Above-Knee Replantation Following Traumatic Bilateral Amputation: Sciatic Nerve Transplantation. AB - A 12-year-old boy who was overrun by a train, sustained traumatic bilateral above knee amputation and a rupture of the symphysis. The left leg had multiple fractures and soft tissue injuries and amputation was necessary. The right one, although severely crushed, at the amputation site and with a MESS of 9, was replanted accepting some shortening and a soft tissue defect at the amputation site, employing saphenic vein grafts from the amputate (left leg) and an early free latissimus dorsi-flap. Septic complications at the amputation site were managed, and an autologous sciatic nerve graft was performed 8 months after the accident, employing the contralateral above-knee stump as the donor. Protective foot sole sensitivity was noticed after 2 years and 4 months and continued to improve. Further reconstructive procedures included ORIF of a femoral fracture in the contra-lateral stump. On the replanted leg proximal tibia corrective osteotomy and lateral collateral knee ligament reconstruction were performed. A follow-up of 7 years and 9 months demonstrates now a leg capable of full weight bearing and recovery of overall protective sensitivity. The boy made good psycho social progress after difficulties and feels that the replanted leg is of significantly greater use to him than the hi-tech prosthesis on the other leg. PMID- 26816152 TI - Seat Belt Syndrome and Aortoiliac Lesion: Case Report and Review of the Literature. AB - Blunt vascular trauma represents 7-9% of the vascular lesions in civilians. There are few reports associating blunt trauma with aortoiliac lesion to the trauma associated with the use of seat belts. We report a case of aortic bifurcation disruption and bilateral iliac artery thrombosis directly related to seat belt use and not associated with pelvic fractures. Arterial revascularization was accomplished through an aortoiliac bypass with spiraled saphenous vein interposition graft and perfusion was restored to both limbs. However, the patient died 5 days after due to respiratory distress syndrome. A high index of suspicion and early diagnosis are essential for patient survival and limb salvage. PMID- 26816153 TI - Erratum to Predictors of Death in Trauma Patients who are Alive on Arrival at Hospital. AB - OBJECTIVE: To determine which factors predict death occurring in trauma patients who are alive on arrival at hospital Design Prospective cohort study Method Data were collected from 507 trauma patients with multiple injuries, with a Hospital Trauma Index-Injury Severity Score of 16 or more, who were initially delivered by the Emergency Medical Services to the Emergency Department of the University Medical Centre Utrecht (UMCU) during the period 1999-2000. RESULTS: Univariate analysis showed that every year of age increase resulted in a 2% greater risk of death. If the patient had been intubated at the scene of the accident, this risk was increased 4.3-fold. Every point of increase in the Triage Revised Trauma Score (T-RTS) reduced the risk of death by 30%. A similar (but inverse) tendency was found for the HTI-ISS score, with every point of increase resulting in a 5% greater risk of death. There was a clear relationship between the base excess (BE) and hemoglobin (Hb) levels and the risk of death, the latter being increased by 8% for each mmol/l drop in BE, and reduced by 22% for each mmol/l increase in Hb. The risk of death occurring was 2.6 times higher in cases with isolated neurotrauma. These associations hardly changed in the multivariate analysis; only the relation with having been intubated at the scene disappeared. CONCLUSION: The risk of severely injured accident patients dying after arriving in hospital is mainly determined by the T-RTS, age, presence of isolated neurological damage, BE and Hb level. Skull/brain damage and hemorrhage appear to be the most important causes of death in the first 24 h after the accident. The time interval between the accident and arrival at the hospital does not appear to affect the risk of death. PMID- 26816154 TI - Tibiotalar Arthrodesis with the Tibial Compression Nail. AB - OBJECTIVE: Arthrodesis of the ankle joint in proper position (neutral position in respect to flexion/extension, 5 degrees external rotation, 0-5 degrees of valgus). Pain-free weight bearing of the affected limb. INDICATIONS: Painful osteoarthritis of the ankle joint resistant to conservative approaches even in the presence of poor bone quality of the distal tibia such as after pilon fractures and osteoporosis. Failure of other methods of internal fixation. CONTRAINDICATIONS: Osteitis. Partial necrosis of the talar dome. Medullary canal of tibia not patent. SURGICAL TECHNIQUE: Lateral approach and resection of lateral malleolus. If the joint position is normal, removal of articular cartilage of tibia and talus. If axial correction is necessary, wedge resection of articular surfaces with underlying bone. Opening of proximal tibial medullary canal, insertion of compression nail into tibia and talus. Compression osteosynthesis and cancellous bone grafting. Alternatively, the arthrodesis can be achieved with the dowel technique. RESULTS: Between September 1993 and March 2001, 137 patients (43 women, 94 men, average age 49 years [21-79 years]) were operated. Follow-up of 110 patients after 42 months: successful bony fusion in 99 patients (90%). In six patients (5.5%) the goal of treatment was obtained after revision with recompression of the nail and bone grafting. Nonunion in five patients (4.5%). COMPLICATIONS: one tibial shaft fracture, one hematoma needing evacuation, three superficial infections, and eight deep infections. Three patients developed an osteoarthritis of the subtalar joint. 70 patients (63.6%) reported an improvement, 37 (33.6%) no notable change of symptoms, and three (2.7%) a deterioration. PMID- 26816157 TI - Drug abuse and addiction from the public health standpoint. PMID- 26816158 TI - [The dual commitment of an outpatient clinic specialized in chemical dependency of the Brazilian Navy: to the patients and to the institution]. AB - A pioneering study conducted at the Center for Chemical Dependency (CEDEQ) of the Brazilian Navy (MB), by means of an ethnographic study with participant observation, investigated the influence of MB in the identification of alcoholism among patients. This article presents one of the research results, namely the dual commitment of this Outpatient Clinic to the patients and to the institution. The results encompass topics such as the organization and functioning of CEDEQ, therapeutic contract, anonymity and confidentiality, discharge, relapses, readmission and abandonments, secondary gains, "scams" and sanctions in addition to the ambiguous perceptions about treatment. In essence, these findings clarify a little more about the institutional intricacies that contribute to lead many patients to alcoholism. PMID- 26816159 TI - Risk of alcohol dependence: prevalence, related problems and socioeconomic factors. AB - The present study evaluated the possible alcohol dependence and related problems among adolescents and determined possible associations with socioeconomic factors and gender. A cross-sectional study was conducted with a representative sample of 936 adolescents aged 15 to 19 years enrolled at public and private schools in the city of Belo Horizonte, Brazil. Data related to alcohol consumption and associated problems were collected using the Alcohol Use Disorder Identification Test (AUDIT). The Social Vulnerability Index (SVI), mother's schooling and type of school were used to assess socioeconomic factors. Statistical analysis involved the chi-square test (p < 0.05) and Poisson regression. The prevalence of possible dependence was 16.4%, 52.1% reported concern of a family member regarding the adolescent's alcohol consumption. Female adolescents were less likely to exhibit possible dependence in comparison to males. Participants with living in a low vulnerability area were more likely to consume alcohol in comparison to those living in underprivileged areas. The results of the present study demonstrate that possible dependence was significantly associated with the male gender and low social vulnerability. PMID- 26816160 TI - Patterns of alcohol use in an elderly sample enrolled in the Family Health Strategy program in the city of Porto Alegre, Brazil. AB - This article aims to determine the pattern of alcohol use in the elderly and its associations with sociodemographic characteristics in an elderly sample of patients from the city of Porto Alegre, Rio Grande do Sul, Brazil. A cross sectional study was conducted involving 557 seniors, aged 60 years or more, through application of the Mini International Neuropsychiatric Interview and a global assessment questionnaire for the elderly. The majority of the 557 senior citizens did not complete elementary school (58.3%), were white (65.1%), married (37.6%), had no caregiver (62.2%), were catholic (65.5%) and practicing their religion (68.6%), were retired (67.7%), and had a personal income of up to one minimum salary (56.1%). The study revealed 67 (12%) elderly people with a history of alcoholism, of which 17 (3.1%) had a diagnosis of current alcoholism, 50 (9%) had a history of alcohol dependence in the past and 16 (2.9%) had a current alcohol abuse problem. Men had a prevalence ratio of 11.6 times for a history of alcoholism in comparison to women. The results confirm that alcoholism is frequent in the population of Brazilian elderly, drawing attention to some socio demographic characteristics that can make a difference in the early diagnosis of alcoholism. PMID- 26816161 TI - Years of life lost (Yll) attributable to alcohol consumption in Mexico City. AB - The aim of this study was to estimate the YLL attributable to alcohol consumption in Mexico City from 2006 - 2012. Vital statistics on mortality attributable to alcohol consumption from the INEGI (Instituto Nacional de Estadistica y Geografia) were used to determine YLL as well as the average age of death in relation to different age ranges by sex. A total estimate of 168,607 YLL was obtained, with an average loss of 18.32 years being observed for men and 17.54 years for women. Men accounted for a higher proportion of the YLL than women. According to the ICD-10 (Tenth Revision of International Classification of Diseases), liver disease attributable to alcohol consumption was found to be responsible for more than 80% of the total YLL. There was a cyclical trend in YLL from 2006 to 2012. The YLL attributable to alcohol suggest that alcohol consumption is a public health problem that involves losses in productivity and economic costs, and the decline in YLL could be explained by the decrease in income caused by the economic crisis of 2008, just as the increase could be explained by economic improvement in 2012. PMID- 26816162 TI - Smoking and poverty in Brazil: an analysis of the profile of the smoking population based on the 2008-09 Brazilian government Family Budget Survey. AB - This paper aims to characterize the Brazilian population who spent money with tobacco products. POF dataset was used from IBGE of the years 2008 and 2009. The same definition that IBGE usually use for tobacco consumer was applied, which is someone has spent money with any kind of tobacco products and its derivatives. It was used individual aspects taking into account such as gender, schooling, age (over 14 years old), income lines, regions and ethnics to characterize these populations. Descriptive statistics were employed to estimate the results and the complex sample design of the survey was considered. According to our results, on average, 10% of the Brazilian population have spent money with tobacco products. Besides, these people are older, earn low salaries and have less schooling than someone who does not consume tobacco. Moreover, for this population 1.5% of the family budget is spent on tobacco products. Last but not least, the most of tobacco consumers are men. In general, money which is spent on tobacco products can cause impressive effects on domestic budget because this value could supply other important necessities to the family. Although there are many monitoring and prevention strategies to avoid tobacco consume, deep knowledge about this population that actually consume these products can increase the efficacy of more specific policies. PMID- 26816163 TI - [Economic factors and gender differences in the prevalence of smoking among adults]. AB - This article presents a study that seeks to identify the relevant economic variables in the prevalence of smoking in a group of 37 countries. The chosen methodology was to estimate multiple linear regression using the least square approach. The econometric exercise is performed by gender, seeking to examine whether there are different motivations for cigarette smoking among the adult population of men and women. The results show that although taxation is a common element in the decision of both sexes, the decision to smoke among women is also sensitive to price and other social and cultural factors. These factors were based on the fact that women who live in countries that are part of the Organization for Economic Cooperation and Development reveal a significantly higher prevalence of cigarette consumption. The evidence presented in this study, therefore, reinforces the perception that taxation is in fact a crucial tool in the control of smoking, but in the specific case of women, higher prices and the promotion of greater equality with men, are also important. PMID- 26816164 TI - [Leisure-time physical activity and licit substance use in a population sample of young adults]. AB - The scope of this study was to assess the prevalence and factors associated with leisure-time physical activity, as well as to verify its association with licit substance use in a population sample of young adults. It is a cross-sectional population-based study with young adults aged between 18 and 35 years old, living in the urban area of the city of Pelotas in the Brazilian State of Rio Grande do Sul. Sample selection was performed by clusters, being composed of 1953 individuals, among the 82 selected census tracts. The practice of physical activity was evaluated using the International Physical Activity Questionnaire (IPAQ). The chi-square and Poisson regression tests were used for statistical analysis. The prevalence of young adults active in leisure-time physical activity was 25.3%; most were single males between 18 and 23 years, belonging to the people in the highest economic bracket and not smoking on a daily basis. Specific strategies should be developed to promote an active and healthy lifestyle, focusing on incentives for older, lower income class women who smoke. PMID- 26816165 TI - Access to treatment for those with alcohol, crack or other drug dependency problems--a case study in the municipality of Rio de Janeiro, Brazil. AB - Changes in psychiatric policies has meant more emphasis on the protection of the individual's rights, tougher regulations and disincentives regarding involuntary patient admissions, and the creation of a community network to support individuals needing help. The differing socioeconomic status of those requiring treatment coupled with guidelines issued by the Health Ministry has meant that more support and care is now being directed towards individuals and families. The rise in public awareness of the problems in these areas has aided in the changes that have taken place. Due to a lack of community public services, this has led to the proliferation of different types of services all with differing standards of care and has fueled the public debate surrounding involuntary patient admissions. Our analysis in relation to treatment for those with alcohol, crack and other drugs problems in the municipality of Rio de Janeiro, states that there are gaps related to access for all-day public services and a lack of psychiatrists in multi-disciplinary teams. There are many new and untried serviced offered by the private sector, religious bodies and public shelters which have arisen in the wake of the rise in people that need help. We took note of the development and progress of these new projects as well as the policy recommendations from the Government. PMID- 26816166 TI - [Consumption of anxiolytic benzodiazepines: a correlation between SNGPC data and sociodemographic indicators in Brazilian capitals]. AB - The scope of this article is to determine the distribution and frequency of consumption of anxiolytic benzodiazepines and the correlation between consumption and demographic, epidemiological, economic and social characteristics. It is an ecological study with a sample of 27 state capitals. Data collection was performed through the ANVISA database for the dispensation of Alprazolam, Bromazepam, Clonazepam, Diazepam and Lorazepam in 2010-2012, the 2010 Demographic Census (IBGE), DATASUS and Medical Demographic Research. Descriptive statistical analysis and multiple linear regression analyses were performed for data analysis. The northern region has capitals with the lowest and the southeast has capitals with the highest average consumption of these products. The average consumption for the population of all capitals was 3.60 DHD. Alprazolam is the drug most dispensed by pharmacies and private drugstores with average 2.00 DHD for the capitals. Multiple linear regression analysis showed that 76% of the variation was explained by population density (beta = 0.310 p = 0.045) and percentage of physicians (beta = 0.507 p = 0.016). The consumption of short half life anxiolytics has been on the increase, mainly in the cities of greater population density and concentration of physicians. PMID- 26816167 TI - [Evaluation of the Brazilian version of the CRAFFT/CESARE scale for screening drug use by adolescents]. AB - The scope of this article is to present the Brazilian version of the CRAFFT scale for screening drug use among adolescents and to assess its comprehensibility. It is a descriptive and quantitative study, which evaluated the applicability of the Brazilian version of the CRAFFT scale through a convenience sample of adolescents aged 14-21 enrolled at two technical schools. Three main aspects were evaluated: difficulty in understanding the scale; the validity of the translated scale comparing a subsample (28,8%) that also filled out the CEBRID questionnaire; and the percentage of adolescents who scored positive on the CRAFFT/CESARE using the pre-established cutoff point. The kappa coefficient was applied to establish correspondence between questionnaires and the ROC curve was used to evaluate the psychometric differences within different cutoffs. The CRAFFT/CESARE scale was applied in 2005 students, of which 1882 are within the defined age bracket. Only 2.2% of adolescents had difficulty in understanding the questions. The specificity of the CRAFFT/CESARE scale was 73.3%, and sensitivity was 87.1%. The concordance degree (Kappa) was considered good (0.461). The CRAFFT/CESARE scored positive in 36.2% of the adolescents. PMID- 26816168 TI - Family functioning and health issues associated with codependency in families of drug users. AB - Substance abuse affects both the user and the family system as a whole, yet substance abuse treatment is centered on the user, leaving the family in the background. OBJECTIVE: To identify the symptoms of codependency and health issues in the codependent family members of drug users who called a toll-free telephone counseling service. In total, 505 family members participated in this cross sectional study. Drug users' mothers and wives who had less than 8 years of education and those who were unemployed had a greater chance of high codependency. It was also determined that a high level of codependency imposed a significant burden on the physical and emotional well-being of those affected, resulting in poor health, reactivity, self-neglect and additional responsibilities. It was concluded that codependency has a negative impact on the family system and on the health of the family members of drug users. PMID- 26816169 TI - Intercultural health: proposals, actions and failures. AB - During the 1980s, 1990s and early 2000s,various intercultural health proposals and actions emerged in most Latin American countries. These initiatives aimed to integrate biomedicine with traditional medicine based on 'parallel' relationships, as opposed relationships based on exclusion, subordination and hegemony. These initiatives had two basic objectives:1) to contribute to the cultural rehabilitation of ethnic groups that made effective use of traditional medicine; and 2) to improve the quality of relationships between health professionals and indigenous patients. This paper analyzes the reasons for the limited impact and, in some cases, failure of such intercultural health initiatives. PMID- 26816170 TI - Family and community orientation in children's primary healthcare. AB - This article seeks to identify the principle of family and community orientation in Family Health Units, relating to care for the health of children under the age of 10. It is a quantitative, assessment study of 344 family members and/or carers of children under the age of 10, served in the 53 Family Health units of the 3rd ('IIIrd') Health District of the city of Joao Pessoa, Brazil. The data were collected based on the Family Orientation and Community Orientation variables present in the children's version of the Primary Care Assessment Tool - Brasil. Analysis took the form of simple frequency distribution statistics. Average scores for the components analyzed were between 3.7 and 5.7, lower than the level of 6.6 which is determined for these attributes to be oriented to primary healthcare. There is a weak orientation of the attributes Family Orientation and Community Orientation in the primary care of the services evaluated, and this indicates a need for a full approach to the child, with macro- and micro political conceptions by those planning and managing healthcare, to ensure that children get full and effective healthcare. PMID- 26816171 TI - Childhood and [re]habilitation: pragmatic political realities in the Colombian context. AB - In this article, we outline some intersections between the concepts of childhood and [re] habilitation, which have undergone parallel development, especially since the 20th century. This complex interaction is mediated and constructed from scientific discourses that have consolidated around childhood. We emphasize this analysis from two perspectives: 1) academic positions that, from professions such as physical therapy, speech therapy, and occupational therapy, touch upon [re]habilitation in childhood and 2) public policy perspectives, which tend towards the creation of places to professionally practice [re]habilitation. A literature review driven by the question "What does it mean to [re]habilitate children in Colombia?" is cited in each section of this text, divided historically into 1) the rise of these [re]habilitative professions in Colombia, 2) the decade of the 1990s, marked by great changes through Colombian political reforms, and 3) the technological developments of the 21st century. We conclude that medical hegemony continues to guide the processes of [re]habilitation within a context that has changed and which imposes new challenges and requires new understanding and great conceptual and practical mobilization. PMID- 26816172 TI - [Methods of a posteriori identification of food patterns in Brazilian children: a systematic review]. AB - The objective of this study is to provide guidance for identifying dietary patterns using the a posteriori approach, and analyze the methodological aspects of the studies conducted in Brazil that identified the dietary patterns of children. Articles were selected from the Latin American and Caribbean Literature on Health Sciences, Scientific Electronic Library Online and Pubmed databases. The key words were: Dietary pattern; Food pattern; Principal Components Analysis; Factor analysis; Cluster analysis; Reduced rank regression. We included studies that identified dietary patterns of children using the a posteriori approach. Seven studies published between 2007 and 2014 were selected, six of which were cross-sectional and one cohort, Five studies used the food frequency questionnaire for dietary assessment; one used a 24-hour dietary recall and the other a food list. The method of exploratory approach used in most publications was principal components factor analysis, followed by cluster analysis. The sample size of the studies ranged from 232 to 4231, the values of the Kaiser Meyer-Olkin test from 0.524 to 0.873, and Cronbach's alpha from 0.51 to 0.69. Few Brazilian studies identified dietary patterns of children using the a posteriori approach and principal components factor analysis was the technique most used. PMID- 26816173 TI - [Public health policies for the intellectually disabled in Brazil: an integrative review]. AB - This study presents an integrative review of the scientific literature and federal legislation on public health policies for intellectually disabled in Brazil. Nine articles, published in the PubMed, Scopus, Virtual Health Library and Web of Science databases between 2002 and 2012, were selected. Based on the references of these studies, 6 other articles were identified, totaling 15 studies in the review. Forty-one federal laws produced between 2002 and 2012 were identified. The documents were analyzed and categorized according to the main themes of socioeconomic conditions, violence, mental health, ethics, health needs, health promotion and prevention. From the scientific standpoint, non specific discussions were observed where intellectual disability was examined with other types of handicaps or concomitantly with other Latin American countries. From the legal standpoint, although laws related to health have been located, there is a lack of studies that address the effectiveness and level of implementation of the proposed policies. The increase in research in this area is a demand of the disabled population itself, and will reveal their specific health needs, and will also support issues such as prevention, promotion, diagnosis and treatment. PMID- 26816174 TI - The socio-ecological and primary care approach to the creation of universal health systems in the work of Hernan San Martin. AB - This article describes the contributions of Chilean physician San Martin Ferrari (1915-200), arguing that they constitute important cornerstones in collective health in Brazil, Latin America, and the Iberian Peninsula. His work is reviewed, establishing a dialog with the current theoretical research in this field and the context of contemporary health systems. Two main aspects are emphasized: the innovation of San Martin in insisting on the importance of analyses that incorporate the relationship between environment and health; and his role in the creation of the Chilean and the Spanish National Health Services. Although they arose in distinct moments and had different trajectories, these systems constitute examples for the creation of universal public health systems, such as the Brazilian health reform and the ongoing challenge to improve the Unified Health System. The analysis of his work and biography contribute elements for the comparative study of these reforms, as well as an eco-systemic approach to health. PMID- 26816175 TI - The therapeutic itinerary in urgent/emergency pediatric situations in a Maroon community. AB - The goal was to understand the therapeutic itinerary of Maroon children in urgent/emergency situation. Is a descriptive research with a qualitative approach that uses the Health Care System model of Arthur Kleinman as its theoretical support. Participants included 12 mothers of children who had experienced any urgent or emergency medical situation. Data collection took place from December 2013 to June 2014 through semi-structured interviews with a thematic analysis of the data. The care of the child started in the "informal" subsystem, and access to a "formal" subsystem was characterized as a pilgrimage for health services. A development of specific strategies is needed to ensure and facilitate full access to the services of the professional subsystem for Maroon communities. PMID- 26816176 TI - [Maternal near misses and health inequalities: an analysis of contextual determinants in the State of Rio Grande do Norte, Brazil]. AB - The scope of this study was to identify socioeconomic contextual and health care factors in primary care associated with maternal near misses and their marker conditions. This is an ecological study that used aggregated data of 63 clusters formed by the municipalities of State of Rio Grande do Norte, Brazil, using the Skater method of area regionalization, as the unit of analysis. The ratio of maternal near misses and their marker conditions were obtained from the Hospital Information System of the Brazilian Unified Health System. In multiple linear regression analysis, there was a significant association between maternal near misses and variables of poverty and poor primary health care. Hypertensive disorders were also associated with poverty and poor primary care and the occurrence of hemorrhaging was associated with infant mortality. It was observed that the occurrence of maternal near misses is linked to unfavorable socioeconomic conditions and poor quality health care that are a reflection of public policies that accentuate health inequalities. PMID- 26816177 TI - Group approach for the evaluation of language disorders in young children. AB - The aim of this study was to describe the contributions of a group therapy approach, which had a social interactionist focus, on the evaluation of language in children aged from between one year, nine months and three years. Nine children participated in the study and they were evaluated in three groups of three participants (G1 and G2--children with language disorder problems, G3- children without language disorders). Four video-recorded meetings were performed for each group, each of which lasted from 30 to 60 minutes. The videos were analyzed along with the field journal, focusing on the participation of the children and their oral and non-oral production. This study provides a detailed analysis of G2, which showed an increase in oral production and an expansion of linguistic functions throughout the sessions. The non-verbal aspects contributed to the identification of relevant elements related to language, especially at the pragmatic level. The context of play and group interaction, and even disputes for objects, led to the detection of different aspects of language. The proposed assessment which is described made it possible to observe the children's language in a live context and it is a model that covers the different aspects of language in meaningful contexts of interaction. PMID- 26816178 TI - Isolated and combined presence of elevated anthropometric indices in children: prevalence and sociodemographic correlates. AB - This study analyzed the prevalence and sociodemographic factors associated to the isolated and combined presence of elevated anthropometric indices among children. A cross-sectional study was performed with 2,035 children (aged 6-11 years, 50.1% of girls) who were randomly selected in schools from Colombo, Brazil. Body Mass Index (BMI), Waist Circumference (WC) and Waist-to-Height Ratio (WHtR) were classified using reference values. Age, gender, type of school, shift, and residence area were potential risk factors. Binary logistic regression was used (p < 0.05). The prevalence of children with isolated presence of elevated BMI, WHtR or WC was observed in 9.4% (confidence interval [CI] of 95%: 3.3; 15.7), 8.7% (CI 95%: 1.7; 15.9) and 4.4% (CI 95%: 1.0; 7.9), 8.7% of children, respectively. The presence of one or more elevated anthropometric index was observed in 16.9% (CI 95%: 5.4; 28.5) of children. Boys (BMI), younger children (WC) and children from public schools (BMI, WC or WHtR) were high-risk subgroups to the isolated presence of elevated anthropometric indices. Children from public schools and rural areas were high-risk subgroup to the combined presence of elevated anthropometric indices. In conclusion, Public policies to combat childhood obesity may be more effective whether they targeted at children from public schools and rural areas. PMID- 26816179 TI - The context of leprosy in Brazil-Paraguay border. AB - In Brazil, leprosy is endemic in three regions: the North, Northeast, and Mid West. Counties with contiguous binational urban areas are characterized by a constant flow of people, goods, and services, which facilitates the transmission of diseases and influences the epidemiological profile of leprosy. The purpose of this study was to examine territorial differences in relation to the incidence of leprosy, focusing on border counties with contiguous binational urban areas or otherwise. Each county was taken as an information unit for leprosy cases reported during 2001-2011, based on data from original notification records of the state's Department of Health. In counties with contiguous binational urban areas detection rates showed tendency to increase, Virchowian (lepromatous) disease and disability grade II predominated when compared with Groups II and III: 0.64 and 0.54/100,000 inhabitants for Virchowian disease and 0.14 and 0.27/100,000 inhabitants for disability grade II respectively, and were associated with higher transmission rates. The findings demonstrate the role of border areas in maintaining the endemicity of leprosy. PMID- 26816180 TI - [Temporal trends of preterm birth and its determinants over a decade]. AB - This study sought to analyze the frequency of preterm births and identify the respective risk factors and their evolution over a decade (2001-2005-2010) in a city in Sao Paulo state. It is a time-series study using data from the Live Birth Information System. Univariate and multiple logistic regression were used to identify factors associated with preterm births, and linear regression was used to evaluate the time-series tendency of such factors in the period. To avoid underestimation, a correction factor was applied to the preterm frequencies obtained. A discrete increase in preterm birth was observed: 12.5%, 12% and 13.2%. After adjusting for confounding factors, maternal age equal to or higher than 35 years and cesarean sections were associated with higher chances for preterm births and increased over the decade. The number of births in high-risk hospitals and of women with fewer than seven prenatal consultations decreased during the period, while multiple pregnancies remained stable. Compared to vaginal births, cesarean sections doubled the chance of preterm birth. Among the five factors associated with preterm birth, three (cesarean sections, births in high-risk hospitals and fewer than seven prenatal consultations) can be modified by actions taken by health care services. PMID- 26816181 TI - Childcare in the neonatal period: evaluation of neonatal mortality reduction pact in rio Grande do Norte, Brazil. AB - The objective was to evaluate the childcare actions in the neonatal period from the strategies recommended by the Ministry of Health. Cross-sectional study carried out from the database of the national population-based survey entitled "Chamada Neonatal" (Neonatal Call--in English): assessment of attention to prenatal care and to children under one year in the North and Northeast, which happened in the nine priority municipalities for the Pact of reducing child mortality and Neonatal in Rio Grande do Norte, Brazil with 837 mother/child pairs. The variables were composed by issues/actions regarding the neonatal period, followed by a descriptive and inferential analysis. The whole database sample was used, composed of 57.6% in the capital and 42.4% in all the interiors. The frequency of hospital environment actions ranges from 35% to 96% and those carried out in primary care from 57% to 91.2%. Most are associated with the nature of public hospitals and the state capital, and the actions of care for continuity of care and better economic conditions (p <0.05). Not all actions met the totality of what is advocated in the programs and childcare policies, and reveals regional inequalities in healthcare. PMID- 26816182 TI - [Regional inequalities in cervical cancer mortality in Brazil: trends and projections through to 2030]. AB - The scope of this article is to analyze the temporal trends of cervical cancer mortality in Brazil and calculate the projection of mortality through to the year 2030. Deaths that occurred within the 1996-2010 period were analyzed (Mortality Information System). Mortality trend analysis utilized the Joinpoint regression, while Nordpred was utilized for the calculation of projections. For Brazil, decreasing trends were identified (APC = 1.7% CI95%-2.2; -1.1 p < 0.05). The Midwest region presented a significant reduction trend (APC = -1.3% per year), along with the Southeast (APC = -3.3%) and South (APC = -3.9%) regions. The North and Northeast regions presented stable trends. The states of Acre (APC = -6.5%) and Rio Grande do Sul (APC = -4.1%) presented the most pronounced reduction trends. Analysis of the mortality projections revealed a reduction in mortality rates, starting from the first projected period, with a considerable reduction for the South region. Mortality rates through to the year 2030 are explained, principally, by reductions in the risk of the disease. Cervical cancer mortality presents reducing trends, however these are unequally distributed throughout the country, where the North and Northeast regions present the highest mortality rates. PMID- 26816183 TI - [The impact of climate change on leishmaniasis in Brazil]. AB - This paper sought to assess how climate change will affect the proliferation of leishmaniasis in Brazil in three time frames: 2010-2039, 2040-2079 and 2080-2100, and with two climate change scenarios. The relation of temperature, precipitation and the number of hospital admissions due to leishmaniasis was estimated and projections were made using these results. Results show that precipitation has a strong relation with leishmaniasis incidence and projections show that by the end of the twenty-first century there will be a 15% growth in the annual number of hospital admissions due to leishmaniasis in Brazil, compared to the base scenario (1992-2002). In regional terms, projections indicate growth in every region, with the exception of the Mid-West. The highest relative growth will be in the South of the country, while the highest increase in absolute terms will be observed in the Northeast region. In general, the incidence of leishmaniasis will grow in Brazil due to climate change. PMID- 26816184 TI - Demographic and health attributes of the Nahua, initial contact population of the Peruvian Amazon. AB - We present the case of the Nahua population of Santa Rosa de Serjali, Peruvian Amazon's population, considered of initial contact. This population consists of human groups that for a long time decided to live in isolation, but lately have begun living a more sedentary lifestyle and in contact with Western populations. There are two fully identified initial contact groups in Peru: the Nahua and the Nanti. The health statistics of the Nahua are scarce. This study offers an interpretation of demographic and epidemiological indicators of the Nahua people, trying to identify if a certain degree of health vulnerability exists. We performed a cross sectional study, and after analyzing their health indicators, as well as the supplemental qualitative analysis of the population, brought us to conclude that in 2006, the Nahua, remained in a state of health vulnerability. PMID- 26816185 TI - Characterization of enzymatic profiles of Aedes aegypti strains from the State of Rio Grande do Norte, Brazil. AB - This study was conducted in four strains of Aedes aegypti mosquitoes to evaluate the enzymatic activity profiles in the city of Mossoro, Rio Grande do Norte, and correlate them with biochemical mechanisms of resistance to insecticides. Mosquitos were used to quantify the following detoxification enzymes: Mixed Function Oxidase (MFO), PNPA-esterase (PNPA-EST), and Acetylcholinesterase (AChE). The profiles were compared statistically with profiles from the Rockefeller strain, through the Kruskal-Wallis test and Dunn's multiple comparisons (p < 0.05). The 99 percentile of the values of enzyme activity from the reference strain was calculated for each enzyme, and the percentage of individuals above the 99 percentile was quantified. The enzyme activities were classified as "Unchanged" (< 15%), "Identified change" (> 15% and < 50%), and "Substantially changed" (> 50%). The statistical analysis revealed significant differences in the MFO and AChE profiles, which are fundamental in the determination of profiles of resistance to insecticides. Three populations were classified as "Substantially changed" for MFO. The altered enzymatic activity showed that the changes could have an important role in exposing resistance to insecticides. PMID- 26816186 TI - [Knowledge of modifiable risk factors for cardiovascular disease among women and the associated factors: a population-based study]. AB - The scope of this study was to evaluate the knowledge of modifiable risk factors for cardiovascular disease and its distribution in terms of demographic, socioeconomic, behavioral and biological factors among women living in the State of Rio Grande. It was a cross-sectional population-based study, with the inclusion of women aged 18 years and over. Descriptive, bivariate and multivariable Poisson Regression analysis were performed. The outcome was defined as knowing three or more of the seven risk factors studied (75th percentile). Of the 1,593 respondents, 33% knew three or more factors. The outcome was independently associated with increased likelihood of knowledge among subjects in the 25-44 years old age group, non-white skin color, complete secondary education, higher income and having cardiovascular disease. On the other hand, sedentary women were less likely to have such knowledge. These findings indicate the need for educational activities for enhancing comprehension and knowledge of the factors associated with cardiovascular disease among women, particularly among the poorest and less educated. PMID- 26816187 TI - [The moderator role of family type in the relationship between functional disability and quality of life in patients with chronic low back pain]. AB - Chronic low back pain is a disease that interferes with quality of life and the patient's functional capability. This study aimed to identify the moderating effect of the "Type of Family" in the relationship between functional disability and quality of life in patients with chronic low back pain. Two hundred and three patients with low back pain for longer than 3 months participated in the study. The instruments used were: Medical Outcome Study (MOS 20); Roland Morris Disability Questionnaire (RMDO; Family Adaptability and Cohesion Evaluation Scales (FACES II). Regression analyses were performed in order to test the moderating effect of the type of family. The results showed that patients with lower levels of disability presented better quality of life in the intermediate and balanced families, and this relationship was even stronger in balanced families. According to the results, intervention programs in chronic low back pain, besides the patient, should include the family particularly in balanced families since they are the ones that feel the impact of the disease on their quality of life the most. PMID- 26816189 TI - Selective Formation of Conductive Network by Radical-Induced Oxidation. AB - Cd-based coordination networks having channels were formed selectively by using a redox-active aromatic ligand 2,5,8-tri(4-pyridyl)1,3-diazaphenalene (TPDAP, H(+)1(-)). An electron-conductive network having a pi-pi stacking columnar structure of TPDAP formed in the presence of a trace amount of TPDAP radical (1(*)). In contrast, a nonconductive network having a dimer unit of H(+)1(-) formed in the absence of 1(*). These results suggest the presence of a unique oxidation mechanism of TPDAP induced by formation of H(+)1(-)-1(*) dimer, which was initiated by a trace amount of 1(*). The dimerization increased HOMO level of H(+)1(-) moiety within the dimer to generate further radicals that could not form when H(+)1(-) was well isolated in CH3OH. PMID- 26816190 TI - Prospects of Graphene as a Potential Carrier-Transport Material in Third Generation Solar Cells. AB - Third-generation solar cells are understood to be the pathway to overcoming the issues and drawbacks of the existing solar cell technologies. Since the introduction of graphene in solar cells, it has been providing attractive properties for the next generation of solar cells. Currently, there are more theoretical predictions rather than practical recognitions in third-generation solar cells. Some of the potential of graphene has been explored in organic photovoltaics (OPVs) and dye-sensitized solar cells (DSSCs), but it has yet to be fully comprehended in the recent third-generation inorganic-organic hybrid perovskite solar cells. In this review, the diverse role of graphene in third generation OPVs and DSSCs will be deliberated to provide an insight on the prospects and challenges of graphene in inorganic-organic hybrid perovskite solar cells. PMID- 26816191 TI - An empirical model for calculation of the collimator contamination dose in therapeutic proton beams. AB - Collimators are used as lateral beam shaping devices in proton therapy with passive scattering beam lines. The dose contamination due to collimator scattering can be as high as 10% of the maximum dose and influences calculation of the output factor or monitor units (MU). To date, commercial treatment planning systems generally use a zero-thickness collimator approximation ignoring edge scattering in the aperture collimator and few analytical models have been proposed to take scattering effects into account, mainly limited to the inner collimator face component. The aim of this study was to characterize and model aperture contamination by means of a fast and accurate analytical model. The entrance face collimator scatter distribution was modeled as a 3D secondary dose source. Predicted dose contaminations were compared to measurements and Monte Carlo simulations. Measurements were performed on two different proton beam lines (a fixed horizontal beam line and a gantry beam line) with divergent apertures and for several field sizes and energies. Discrepancies between analytical algorithm dose prediction and measurements were decreased from 10% to 2% using the proposed model. Gamma-index (2%/1 mm) was respected for more than 90% of pixels. The proposed analytical algorithm increases the accuracy of analytical dose calculations with reasonable computation times. PMID- 26816192 TI - Stability of daily preference across multiple individuals. AB - Preference stability provides clues about the extent to which a clinician might be able to deliver a particular stimulus contingent on behavior as a reinforcer. Previous research has been somewhat mixed in terms of evidence for preference stability. Results of the current study are consistent with studies that have reported correlations between preference assessments, suggesting that preferences are relatively stable across time. PMID- 26816193 TI - Imaging of brain TSPO expression in a mouse model of amyotrophic lateral sclerosis with (18)F-DPA-714 and micro-PET/CT. AB - PURPOSE: To evaluate the feasibility and sensitivity of (18)F-DPA-714 for the study of microglial activation in the brain and spinal cord of transgenic SOD1(G93A) mice using high-resolution PET/CT and to evaluate the Iba1 and TSPO expression with immunohistochemistry. METHODS: Nine symptomatic SOD1(G93A) mice (aged 117 +/- 12.7 days, clinical score range 1 - 4) and five WT SOD1 control mice (aged 108 +/- 28.5 days) underwent (18)F-DPA-714 PET/CT. SUV ratios were calculated by normalizing the cerebellar (rCRB), brainstem (rBS), motor cortex (rMCX) and cervical spinal cord (rCSC) activities to that of the frontal association cortex. Two WT SOD1 and six symptomatic SOD1(G93A) mice were studied by immunohistochemistry. RESULTS: In the symptomatic SOD1(G93A) mice, rCRB, rBS and rCSC were increased as compared to the values in WT SOD1 mice, with a statistically significantly difference in rBS (2.340 +/- 0.784 vs 1.576 +/- 0.287, p = 0.014). Immunofluorescence studies showed that TSPO expression was increased in the trigeminal, facial, ambiguus and hypoglossal nuclei, as well as in the spinal cord, of symptomatic SOD1(G93A) mice and was colocalized with increased Iba1 staining. CONCLUSION: Increased (18)F-DPA-714 uptake can be detected with high-resolution PET/CT in the brainstem of transgenic SOD1(G93A) mice, a region known to be a site of degeneration and increased microglial activation in amyotrophic lateral sclerosis, in agreement with increased TSPO expression in the brainstem nuclei shown by immunostaining. Therefore, (18)F-DPA 714 PET/CT might be a suitable tool to evaluate microglial activation in the SOD1(G93A) mouse model. PMID- 26816194 TI - Reduction in camera-specific variability in [(123)I]FP-CIT SPECT outcome measures by image reconstruction optimized for multisite settings: impact on age dependence of the specific binding ratio in the ENC-DAT database of healthy controls. AB - PURPOSE: Quantitative estimates of dopamine transporter availability, determined with [(123)I]FP-CIT SPECT, depend on the SPECT equipment, including both hardware and (reconstruction) software, which limits their use in multicentre research and clinical routine. This study tested a dedicated reconstruction algorithm for its ability to reduce camera-specific intersubject variability in [(123)I]FP-CIT SPECT. The secondary aim was to evaluate binding in whole brain (excluding striatum) as a reference for quantitative analysis. METHODS: Of 73 healthy subjects from the European Normal Control Database of [(123)I]FP-CIT recruited at six centres, 70 aged between 20 and 82 years were included. SPECT images were reconstructed using the QSPECT software package which provides fully automated detection of the outer contour of the head, camera-specific correction for scatter and septal penetration by transmission-dependent convolution subtraction, iterative OSEM reconstruction including attenuation correction, and camera specific "to kBq/ml" calibration. LINK and HERMES reconstruction were used for head-to-head comparison. The specific striatal [(123)I]FP-CIT binding ratio (SBR) was computed using the Southampton method with binding in the whole brain, occipital cortex or cerebellum as the reference. The correlation between SBR and age was used as the primary quality measure. RESULTS: The fraction of SBR variability explained by age was highest (1) with QSPECT, independently of the reference region, and (2) with whole brain as the reference, independently of the reconstruction algorithm. CONCLUSION: QSPECT reconstruction appears to be useful for reduction of camera-specific intersubject variability of [(123)I]FP-CIT SPECT in multisite and single-site multicamera settings. Whole brain excluding striatal binding as the reference provides more stable quantitative estimates than occipital or cerebellar binding. PMID- 26816196 TI - Three-Mode Factor Analysis Of Parker-Fleishman Complex Tracking Behavior Data. AB - A combination method of analysis utilizing Tucker's generalized learning curves and three-mode factor analysis is tried out on intercorrelations published by Parker and Fleishman of several measures of performance at several stages of practice on a complex tracking task. The results indicated two measure factors, directional control and sideslip control; four stages of practice factors, very early, middle early, middle late, and very late; and seven factors of individual differences corresponding to combinations of measures and stages of practice factors. The results were clear so that the combination method of analysis has promise for indicating the structure of relations in similar data. PMID- 26816197 TI - Behavioral And Personality Expectations Associated With Status Positions. AB - Two parallel studies explore whether status-positions may be character- ized by certain general behaviors and personality traits. Fifty-two status- positions, including selected ethnic, occupational, age, sex, and familial categories, were ranked and rated on twenty-eight personality and behavioral characteristics by substantial samples of college students. Analysis of these data indicated that some behavioral characteristics and personality traits are consistently attributed to particular status-positions independently of method (rating or ranking), with little or no effects attributable to the five orders of presentation used. Factor analysis of the status-positions yielded five factors for both the ratings and the rankings, four of which were interpretable and scored: Likeability, Defiance, Responsibility, and Emotionality. The factor structure found was related to previous research on characteristics of persons. Profiles of the status-positions using mean scores based on these four factors plus assertiveness were presented. PMID- 26816195 TI - Quantitative assessment of atherosclerotic plaques on (18)F-FDG PET/MRI: comparison with a PET/CT hybrid system. AB - PURPOSE: PET with (18)F-FDG has the potential to assess vascular macrophage metabolism. (18)F-FDG is most often used in combination with contrast-enhanced CT to localize increased metabolism to specific arterial lesions. Novel (18)F-FDG PET/MRI hybrid imaging shows high potential for the combined evaluation of atherosclerotic plaques, due to the superior morphological conspicuity of plaque lesions. The purpose of this study was to evaluate the reliability and accuracy of (18)F-FDG PET/MRI uptake quantification compared to PET/CT as a reference standard in patients with carotid atherosclerotic plaques. METHODS: The study group comprised 34 consecutive oncological patients with carotid plaques who underwent both PET/CT and PET/MRI with (18)F-FDG on the same day. The presence of atherosclerotic plaques was confirmed by 3 T MRI scans. Maximum standardized uptake values (SUVmax) for carotid plaque lesions and the average SUV of the blood pool within the adjacent internal jugular vein were determined and target to-blood ratios (TBRs, plaque to blood pool) were calculated. RESULTS: Atherosclerotic lesions with maximum colocalized focal FDG uptake were assessed in each patient. SUVmax values of carotid plaque lesions were significantly lower on PET/MRI than on PET/CT (2.3 +/- 0.6 vs. 3.1 +/- 0.6; P < 0.01), but were significantly correlated between PET/CT and PET/MRI (Spearman's r = 0.67, P < 0.01). In contrast, TBRmax values of plaque lesions were similar on PET/MRI and on PET/CT (2.2 +/- 0.3 vs. 2.2 +/- 0.3; P = 0.4), and again were significantly correlated between PET/MRI and PET/CT (Spearman's r = 0.73, P < 0.01). Considering the increasing trend in SUVmax and TBRmax values from early to delayed imaging time-points on PET/CT and PET/MRI, respectively, with continuous clearance of radioactivity from the blood, a slight underestimation of TBRmax values may also be expected with PET/MRI compared with PET/CT. CONCLUSION: SUVmax and TBRmax values are widely accepted reference parameters for estimation of the radioactivity of atherosclerotic plaques on PET/CT. However, due to a systematic underestimation of SUVmax and TBRmax with PET/MRI, the optimal cut-off values indicating the presence of inflamed plaque tissue need to be newly defined for PET/MRI. PMID- 26816198 TI - The Primary Mental Abilities Of South American Students : A Second Comparative Study Of The Generality Of A Cognitive Factor Structure. AB - In an earlier study, the Primary Mental Abilities (PMAs) of Chinese students studying in American Universities was compared with those of American college students. In the present study, the PMAs of South American college students are compared with the PMAs of the Chinese students. Thirty- one tests (twenty with English instructions and eleven with Spanish instructions) were administered to 92 South American students who were participating in the English Language Institute of the University of Michigan. After treating the South American data by Ahmavaara's transformation analysis, seven factors were matched between the South American and Chinese studies; the congruence indices for the two sets of factors ranged between .953 and .780. PMID- 26816199 TI - Adolescent Morality: Its Differentiated Structure And Relation To Delinquent Conduct. AB - Cluster analysis of a moral values scale based on responses of 100 matched pairs of delinquent (D) and nondelinquent (ND) boys of high school age revealed 4 highly reliable dimensions: 1) Informing or "snitching", 2 )Masculine inadequacy, 3) Identity conflict, and 4) Aggression. On these matched as well as on replicated samples, the results showed that the D SS consider informing on others as more wrong than the ND Ss, while the ND Ss judged behaviors associated with identity conflict as more wrong than the D Ss. Non-significant relationships were found between the moral value dimensions and age, race, social status and verbal intelligence. The results were discussed in relation to previously postulated assumptions concerning the global nature of morality and the direct relation of verbalized moral values and moral behavior. The results were interpreted as being partially consistent with the notion that the delinquent is not necessarily ignorant of societal values but rather becomes committed to or adopts the values of the deviant subculture. PMID- 26816200 TI - Second Stratum Personality Factors Defined In The Questionnaire Realm By The 16 P.F. AB - To determine the factors in the correlations between the 16 P.F. scales on the basis of a heterogeneous sample, a correlation matrix ( N = 1,652) was determined by combining data from several samples. Eight factors were ex- tracted on the basis of mathematical and statistical considerations and rotated to simple structure. The major f a c b r s were Anxiety, Exvia vs. Invia (extraversion vs. intro- version but with limited social orientation), Cool Rationality vs. Pathemia (affectivity), and Independence vs. Subduedness. Smaller factors included Cultured Tact vs. Spontaneity, and Untamedness vs. Sensitive Practicality. The present study suggests that several stable second order factors may possibly be established in addition to the usual ones of Anxiety and Exvia- Invia. PMID- 26816201 TI - Direction Of Measurement And Profile Similarity. AB - Recently, Tellegen (1965), in his discussion of the influence of direction of measurement on the analysis of test characteristics, pointed out that similar problems can exist in the assessment of profile similarity. This paper reports two empirical analyses which demonstrate that the correlations between personality test profiles are meaningfully affected by decisions concerning direction of measurement. Reflection of scales in a profile can alter the mean (elevation), variance (scatter), and manifest shape of each profile in a way which yields nonpredictable variations in the person correlation matrix. It is shown that these variations may alter estimations of factor structure, cluster composition, indices of discrimination, and retest stability. c. PMID- 26816202 TI - Factor Analysis Of Individual Social Desirability Scale Values: Second-Order Analysis. AB - A general social desirability factor emerged at the second-order level when a set of individual social desirability scale values were correlated between subjects (i.e., across items) and factor analysed. However, no such general factor emerged at the second-order level when the individual judgments were correlated between items (i.e., across subjects). PMID- 26816203 TI - The Empirical Anchor Technique : A Simple Experimental Method For Testing The Construct Validity Of Factor Titles. AB - A simple experimental technique is proposed for assessing the construct validity of factor titles. The technique involves writing items which are implicit titles of an emergent factor, adding these items to a cross-validation sample with the hypothesis that the items should load high on the given factor and low on other factors. The results of the cross-validation factor analysis would then give estimates of convergent and discriminant validity of the meaningfulness of the factor titles. PMID- 26816204 TI - Stimulated Emission Depletion Lithography with Mercapto-Functional Polymers. AB - Surface reactive nanostructures were fabricated using stimulated emission depletion (STED) lithography. The functionalization of the nanostructures was realized by copolymerization of a bifunctional metal oxo cluster in the presence of a triacrylate monomer. Ligands of the cluster surface cross-link to the monomer during the lithographic process, whereas unreacted mercapto functionalized ligands are transferred to the polymer and remain reactive after polymer formation of the surface of the nanostructure. The depletion efficiency in dependence of the cluster loading was investigated and full depletion of the STED effect was observed with a cluster loading exceeding 4 wt %. A feature size by lambda/11 was achieved by using a donut-shaped depletion beam. The reactivity of the mercapto groups on the surface of the nanostructure was tested by incubation with mercapto-reactive fluorophores. PMID- 26816205 TI - Health Services Utilization and Payments in Patients With Cancer Pain: A Comparison of Intrathecal Drug Delivery vs. Conventional Medical Management. AB - INTRODUCTION: To compare health services utilization and payments for cancer patients who received an implantable intrathecal drug delivery (IDD) system, consisting of a pump and catheter, vs. conventional medical management (CMM) for the treatment of cancer-related pain. METHODS: This retrospective claims-data analysis compared health services utilization and payments in a population of patients receiving either IDD or CMM for treatment of cancer pain. Patients were propensity score-matched 1:1 based on characteristics including, but not limited to, age, gender, cancer type, comorbid conditions, and health care utilization and payments. RESULTS: From a sample of 142 IDD patients and 3188 CMM patients who met all inclusion/exclusion criteria, 73 matched pairs were obtained. In the year following implant, IDD patients had a consistent trend of lower medical utilization, and total payments that were $3195 lower compared to CMM. CONCLUSIONS: Despite the high initial cost of IDD, this analysis suggests that patients with IDD incur lower medical utilization and payments over the first year post-implant. Further analysis comprised of a larger, longitudinal sample would contribute to health economics and outcomes research, and assist with future practice guideline development. PMID- 26816207 TI - Synthesis of Bridged Heterocycles via Sequential 1,4- and 1,2-Addition Reactions to alpha,beta-Unsaturated N-Acyliminium Ions: Mechanistic and Computational Studies. AB - Novel tricyclic bridged heterocyclic systems can be readily prepared from sequential 1,4- and 1,2-addition reactions of allyl and 3-substituted allylsilanes to indolizidine and quinolizidine alpha,beta-unsaturated N acyliminium ions. These reactions involve a novel N-assisted, transannular 1,5 hydride shift. Such a mechanism was supported by examining the reaction of a dideuterated indolizidine, alpha,beta-unsaturated N-acyliminium ion precursor, which provided specifically dideuterated tricyclic bridged heterocyclic products, and from computational studies. In contrast, the corresponding pyrrolo[1,2 a]azepine system did not provide the corresponding tricyclic bridged heterocyclic product and gave only a bis-allyl adduct, while more substituted versions gave novel furo[3,2-d]pyrrolo[1,2-a]azepine products. Such heterocyclic systems would be expected to be useful scaffolds for the preparation of libraries of novel compounds for new drug discovery programs. PMID- 26816206 TI - Who gets antidotes? choosing the chosen few. AB - An understanding of mechanisms, potential benefits and risks of antidotes is essential for clinicians who manage poisoned patients. Of the dozens of antidotes currently available, only a few are regularly used. These include activated charcoal, acetylcysteine, naloxone, sodium bicarbonate, atropine, flumazenil, therapeutic antibodies and various vitamins. Even then, most are used in a minority of poisonings. There is little randomized trial evidence to support the use of most antidotes. Consequently, decisions about when to use them are often based on a mechanistic understanding of the poisoning and the expected influence of the antidote on the patient's clinical course. For some antidotes, such as atropine and insulin, the doses employed can be orders of magnitude higher than standard dosing. Importantly, most poisoned patients who reach hospital can recover with supportive care alone. In low risk patients, the routine use of even low risk antidotes such as activated charcoal is unwarranted. In more serious poisonings, decisions regarding antidote use are generally guided by a risk/benefit assessment based on low quality evidence. PMID- 26816208 TI - Implementation of Cognitive-Behavioral Substance Abuse Treatment in Sub-Saharan Africa: Treatment Engagement and Abstinence at Treatment Exit. AB - AIMS: This study documented the treatment cascade for engagement in care and abstinence at treatment exit as well as examined correlates of these outcomes for the first certified Matrix Model(r) substance abuse treatment site in Sub-Saharan Africa. DESIGN: This retrospective chart review conducted at a resource-limited community clinic in Cape Town, South Africa, assessed treatment readiness and substance use severity at treatment entry as correlates of the number of sessions attended and biologically confirmed abstinence at treatment exit among 986 clients who initiated treatment from 2009-2014. Sociodemographic and clinical correlates of treatment outcomes were examined using logistic regression, modeling treatment completion and abstinence at treatment exit separately. RESULTS: Of the 2,233 clients who completed screening, approximately 44% (n = 986) initiated treatment. Among those who initiated treatment, 45% completed at least four group sessions, 30% completed early recovery skills training (i.e., at least eight group sessions), and 13% completed the full 16-week program. Approximately half (54%) of clients who provided a urine sample had negative urine toxicology results for any substance at treatment exit. Higher motivation at treatment entry was independently associated with greater odds of treatment completion and negative urine toxicology results at treatment exit. CONCLUSIONS: Findings provide initial support for the successful implementation the Matrix Model in a resource-limited setting. Motivational enhancement interventions could support treatment initiation, promote sustained engagement in treatment, and achieve better treatment outcomes. PMID- 26816210 TI - The Effects of Body Mass on Optimal Load for Power During Resistance Training. PMID- 26816209 TI - Is There an Economical Running Technique? A Review of Modifiable Biomechanical Factors Affecting Running Economy. AB - Running economy (RE) has a strong relationship with running performance, and modifiable running biomechanics are a determining factor of RE. The purposes of this review were to (1) examine the intrinsic and extrinsic modifiable biomechanical factors affecting RE; (2) assess training-induced changes in RE and running biomechanics; (3) evaluate whether an economical running technique can be recommended and; (4) discuss potential areas for future research. Based on current evidence, the intrinsic factors that appeared beneficial for RE were using a preferred stride length range, which allows for stride length deviations up to 3 % shorter than preferred stride length; lower vertical oscillation; greater leg stiffness; low lower limb moment of inertia; less leg extension at toe-off; larger stride angles; alignment of the ground reaction force and leg axis during propulsion; maintaining arm swing; low thigh antagonist-agonist muscular coactivation; and low activation of lower limb muscles during propulsion. Extrinsic factors associated with a better RE were a firm, compliant shoe-surface interaction and being barefoot or wearing lightweight shoes. Several other modifiable biomechanical factors presented inconsistent relationships with RE. Running biomechanics during ground contact appeared to play an important role, specifically those during propulsion. Therefore, this phase has the strongest direct links with RE. Recurring methodological problems exist within the literature, such as cross-comparisons, assessing variables in isolation, and acute to short-term interventions. Therefore, recommending a general economical running technique should be approached with caution. Future work should focus on interdisciplinary longitudinal investigations combining RE, kinematics, kinetics, and neuromuscular and anatomical aspects, as well as applying a synergistic approach to understanding the role of kinetics. PMID- 26816211 TI - The Benefit of Bone Health by Drinking Coffee among Korean Postmenopausal Women: A Cross-Sectional Analysis of the Fourth & Fifth Korea National Health and Nutrition Examination Surveys. AB - PURPOSE: Although the concern about coffee-associated health problems is increasing, the effect of coffee on osteoporosis is still conflicting. This study aimed to determine the relationship between coffee consumption and bone health in Korean postmenopausal women. METHODS: A population-based, cross-sectional study was performed using a nationally representative sample of the Korean general population. All 4,066 postmenopausal women (mean age 62.6 years) from the fourth and fifth Korean National Health and Nutrition Examination Survey (2008-2011), who completed the questionnaire about coffee consumption and had data of dual energy X-ray absorptiometry (DXA) examination. Bone mineral density (BMD) was measured using DXA at the femoral neck and lumbar spine and osteoporosis was defined by World Health Organization T-score criteria in addition to self-report of current anti-osteoporotic medication use. RESULTS: After adjusting for various demographic and lifestyle confounders (including hormonal factors), subjects in the highest quartile of coffee intake had 36% lower odds for osteoporosis compared to those in the lowest quartile (Adjusted odds ratio [aOR] = 0.64; 95% confidence interval [CI], 0.43-0.95; P for trend = 0.015). This trend was consistent in osteoporosis of lumbar spine and femoral neck (aOR = 0.65 and 0.55; P for trend = 0.026 and 0.003, respectively). In addition, age- and body mass index (BMI)-adjusted BMD of the femoral neck and lumbar spine increased with higher coffee intake (P for trend = 0.019 and 0.051, respectively). CONCLUSIONS: Coffee consumption may have protective benefits on bone health in Korean postmenopausal women in moderate amount. Further, prospective studies are required to confirm this association. PMID- 26816212 TI - A Longitudinal Rejection Sensitivity Model of Depression and Aggression: Unique Roles of Anxiety, Anger, Blame, Withdrawal and Retribution. AB - In this longitudinal study, attributional and social processes involved in symptoms of mental health problems (depressive symptoms and aggressive behavior) were identified by investigating anxious and angry rejection sensitivity (RS), causal attributions of self-blame and peer-blame, and responses to rejection threat of withdrawal and retribution. Young adolescents (N = 713, grades 5-7) completed questionnaires three times in their regular classrooms over 14 months. Participants who reported more self-blame for rejection were more likely to withdraw in response to rejection threat, and withdrawal and anxious RS were associated with increased depressive symptoms at T3 relative to T1. In contrast, adolescents higher in the angry form of RS and who reported more peer-blame for rejection were more likely to seek retribution, which in turn was associated with more overt/relational aggressive behavior at T3 relative to T1. Depressive symptom level measured at T1 also was associated with later RS and coping with withdrawal, and aggressive behavior at T1 was associated with later retribution. Sex of the participants did not moderate any longitudinal associations, and only one prospective path, from T1 depressive symptoms to T2 RS anxious, was moderated by age. PMID- 26816213 TI - Regulation of Effector Treg Cells in Murine Lupus. AB - OBJECTIVE: Treg cells need to acquire an effector phenotype to function in settings of inflammation. Whether effector Treg cells can limit disease severity in lupus is unknown. Interferon regulatory factor 4 (IRF-4) is an essential controller of effector Treg cells and regulates their ability to express interleukin-10 (IL-10). In non-Treg cells, IRF-4 activity is modulated by interactions with DEF-6 and its homolog switch-associated protein 70 (SWAP-70). Although mice lacking both DEF-6 and SWAP-70 (double-knockout [DKO] mice) develop lupus, they display normal survival, suggesting that in DKO mice, Treg cells can moderate disease development. The purpose of this study was to investigate whether Treg cells from DKO mice have an increased capacity to become effector Treg cells due to the ability of DEF-6 and SWAP-70 to restrain IRF-4 activity. METHODS: Treg cells were evaluated by fluorescence-activated cell sorting. The B lymphocyte-induced maturation protein 1 (BLIMP-1)/IL-10 axis was assessed by crossing DKO mice with BLIMP-1-YFP-10BiT dual-reporter mice. Deletion of IRF-4 in Treg cells from DKO mice was achieved by generating FoxP3(Cre) IRF-4(fl/fl) DKO mice. RESULTS: The concomitant absence of DEF-6 and SWAP-70 led to increased numbers of Treg cells, which acquired an effector phenotype in a cell-intrinsic manner. In addition, Treg cells from DKO mice exhibited enhanced expression of the BLIMP-1/IL-10 axis. Notably, DKO effector Treg cells survived and expanded as disease progressed. The accumulation of Treg cells from DKO mice was associated with the up-regulation of genes controlling autophagy. IRF-4 was required for the expansion and function of effector Treg cells from DKO mice. CONCLUSION: This study revealed the existence of mechanisms that, by acting on IRF-4, can fine tune the function and survival of effector Treg cells in lupus. These findings suggest that the existence of a powerful effector Treg cell compartment that successfully survives in an unfavorable inflammatory environment could limit disease development. PMID- 26816214 TI - Interacting Effects of Newcastle Disease Transmission and Illegal Trade on a Wild Population of White-Winged Parakeets in Peru: A Modeling Approach. AB - Illegal wildlife-pet trade can threaten wildlife populations directly from overharvest, but also indirectly as a pathway for introduction of infectious diseases. This study evaluated consequences of a hypothetical introduction of Newcastle disease (ND) into a wild population of Peru's most trafficked psittacine, the white-winged parakeet (Brotogeris versicolurus), through release of infected confiscated individuals. We developed two mathematical models that describe ND transmission and the influence of illegal harvest in a homogeneous (model 1) and age-structured population of parakeets (model 2). Infection transmission dynamics and harvest were consistent for all individuals in model 1, which rendered it mathematically more tractable compared to the more complex, age structured model 2 that separated the host population into juveniles and adults. We evaluated the interaction of ND transmission and harvest through changes in the basic reproduction number (R0) and short-term host population dynamics. Our findings demonstrated that ND introduction would likely provoke considerable disease-related mortality, up to 24% population decline in two years, but high harvest rates would dampen the magnitude of the outbreak. Model 2 produced moderate differences in disease dynamics compared to model 1 (R0 = 3.63 and 2.66, respectively), but highlighted the importance of adult disease dynamics in diminishing the epidemic potential. Therefore, we suggest that future studies should use a more realistic, age-structured model. Finally, for the presumptive risk that illegal trade of white-winged parakeets could introduce ND into wild populations, our results suggest that while high harvest rates may have a protective effect on the population by reducing virus transmission, the combined effects of high harvest and disease-induced mortality may threaten population survival. These results capture the complexity and consequences of the interaction between ND transmission and harvest in a wild parrot population and highlight the importance of preventing illegal trade. PMID- 26816215 TI - High Throughput Label Free Measurement of Cancer Cell Adhesion Kinetics Under Hemodynamic Flow. AB - The kinetics of receptor-mediated cell adhesion to extracellular matrix and adherent cell monolayers plays a key role in many physiological and pathological processes including cancer metastasis. Within this process the presence of fluidic shear forces is a key regulator of binding equilibrium and kinetics of cell adhesion. Current techniques to examine the kinetics of cell adhesion are either performed in the absence of flow or are low throughput, limiting their application to pharmacological compound screening or the high throughput investigation of biological mechanisms. We developed a high throughput flow device that applies flow in a multi-well format and interfaced this system with electric cell-substrate impedance sensing (ECIS) system to allow label free detection of cell adhesion. We demonstrate that this combined system is capable of making real time measurements of cancer cell adhesion to extracellular matrix and immobilized platelets. In addition, we examined the dependence of the kinetics of binding of cancer cells on the level of shear stress and in the presence of small molecule inhibitors to adhesion-related pathways. This versatile system is broadly adaptable to the high throughput study of cell adhesion kinetics for many applications including drug screening and the investigation of the mechanisms of cancer metastasis. PMID- 26816216 TI - What would you ideally do if there were no targets? An ethnographic study of the unintended consequences of top-down governance in two clinical settings. AB - Top-down policy directives, such as targets and their associated protocols, may be driven politically rather than clinically and can be described as macro political texts. While targets supposedly provide incentives for healthcare services, they may unintentionally shape practices of accommodation rather than implementation, deflecting practitioners from providing optimal care. Live work activities were observed for two six months periods in a UK NHS Emergency Department and a Mental Health Ward using video and field notes ethnography, with post hoc unstructured interviews for clarification and verification. Sixty-four practitioners were consented. Data were treated as narratives, analysed thematically and theorised using cultural-historical activity theory. The ideal text of patient-centred team working shaped by top-down, politically inspired targets was disrupted, where targets produced unintended consequences. Bottom-up strategies of making meaning of targets in a local context generated sub-texts of resistance, rationalization, and even duplicity that had paradoxical positive effects in generating collaboration and democratic habits. Throughput pressures generated both cross-team conflicts and intra-team identification. What practitioners actually do to make sense of top-down directives is not the same as the ideal expectation framed by targets. Team members pulled together not because of targets but in spite of them, and as a form of resistance to governance. Targets produce unnecessary stress as team members focus on throughput rather than quality of care. Those governing healthcare must look at the unintended consequences of targets. PMID- 26816217 TI - Nanoelectronic primary thermometry below 4 mK. AB - Cooling nanoelectronic structures to millikelvin temperatures presents extreme challenges in maintaining thermal contact between the electrons in the device and an external cold bath. It is typically found that when nanoscale devices are cooled to ~ 10 mK the electrons are significantly overheated. Here we report the cooling of electrons in nanoelectronic Coulomb blockade thermometers below 4 mK. The low operating temperature is attributed to an optimized design that incorporates cooling fins with a high electron-phonon coupling and on-chip electronic filters, combined with low-noise electronic measurements. By immersing a Coulomb blockade thermometer in the (3)He/(4)He refrigerant of a dilution refrigerator, we measure a lowest electron temperature of 3.7 mK and a trend to a saturated electron temperature approaching 3 mK. This work demonstrates how nanoelectronic samples can be cooled further into the low-millikelvin range. PMID- 26816218 TI - TIMP2*IGFBP7 biomarker panel accurately predicts acute kidney injury in high-risk surgical patients. AB - BACKGROUND: Acute kidney injury (AKI) is an important complication in surgical patients. Existing biomarkers and clinical prediction models underestimate the risk for developing AKI. We recently reported data from two trials of 728 and 408 critically ill adult patients in whom urinary TIMP2*IGFBP7 (NephroCheck, Astute Medical) was used to identify patients at risk of developing AKI. Here we report a preplanned analysis of surgical patients from both trials to assess whether urinary tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) accurately identify surgical patients at risk of developing AKI. STUDY DESIGN: We enrolled adult surgical patients at risk for AKI who were admitted to one of 39 intensive care units across Europe and North America. The primary end point was moderate-severe AKI (equivalent to KDIGO [Kidney Disease Improving Global Outcomes] stages 2-3) within 12 hours of enrollment. Biomarker performance was assessed using the area under the receiver operating characteristic curve, integrated discrimination improvement, and category-free net reclassification improvement. RESULTS: A total of 375 patients were included in the final analysis of whom 35 (9%) developed moderate-severe AKI within 12 hours. The area under the receiver operating characteristic curve for [TIMP-2]*[IGFBP7] alone was 0.84 (95% confidence interval, 0.76-0.90; p < 0.0001). Biomarker performance was robust in sensitivity analysis across predefined subgroups (urgency and type of surgery). CONCLUSION: For postoperative surgical intensive care unit patients, a single urinary TIMP2*IGFBP7 test accurately identified patients at risk for developing AKI within the ensuing 12 hours and its inclusion in clinical risk prediction models significantly enhances their performance. LEVEL OF EVIDENCE: Prognostic study, level I. PMID- 26816219 TI - A systematic review of the use of resuscitative endovascular balloon occlusion of the aorta in the management of hemorrhagic shock. AB - BACKGROUND: Torso hemorrhage remains a leading cause of potentially preventable death within trauma, acute care, vascular, and obstetric practice. A proportion of patients exsanguinate before hemorrhage control. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct designed to sustain the circulation until definitive hemostasis. A systematic review was conducted to characterize the current clinical use of REBOA and its effect on hemodynamic profile and mortality. METHODS: A systematic review (1946-2015) was conducted using EMBASE and MEDLINE. Original studies on human subjects, published in English language journals, were considered. Articles were included if they reported data on hemodynamic profile and mortality. RESULTS: A total of 83 studies were identified; 41 met criteria for inclusion. Clinical settings included postpartum hemorrhage (5), upper gastrointestinal bleeding (3), pelvic surgery (8), trauma (15), and ruptured aortic aneurysm (10). Of the 857 patients, overall mortality was 423 (49.4%); shock was evident in 643 (75.0%). Pooled analysis demonstrated an increase in mean systolic pressure by 53 mm Hg (95% confidence interval, 44-61 mm Hg) following REBOA use. Data exhibited moderate heterogeneity with an I of 35.5. CONCLUSION: REBOA has been used in a variety of clinical settings to successfully elevate central blood pressure in the setting of shock. Overall, the evidence base is weak with no clear reduction in hemorrhage-related mortality demonstrated. Formal, prospective study is warranted to clarify the role of this adjunct in torso hemorrhage. LEVEL OF EVIDENCE: Systematic review, level IV. PMID- 26816221 TI - Erratum: Complete resistance after maximal dose of rocuronium. AB - [This corrects the article on p. 175 in vol. 6, PMID: 26312006.]. PMID- 26816220 TI - Measuring Pediatric Bronchoscopy Outcomes Using an Electronic Medical Record. AB - RATIONALE: Bronchoscopy procedures should be tracked for safety, quality improvement, and federal regulations. OBJECTIVE: The aim of this study was to develop and test a method for evaluating flexible bronchoscopy use and outcomes using the electronic medical record (EMR) system in current clinical use at a large children's hospital. METHODS: We created a custom bronchoscopy procedure note for our EMR system (Epic Systems Corporation) to track demographics, bronchoscopist, coordinated procedures, and outcome. Unplanned outcomes in children were defined as a disposition (admission to the hospital or elevation of care) after flexible bronchoscopy that differed from the preoperative plan. Readmissions to the hospital and emergency visits within our hospital system were also tracked electronically. Unplanned outcomes and readmissions were evaluated by a bronchoscopy quality team. MEASUREMENTS AND MAIN RESULTS: Over 2.5 years, we tracked 1,297 bronchoscopic procedures performed on 1,161 patients (60% male, 78% American Society of Anesthesiologists class 2 or 3, mean age 5.5 yr [range, 0.02 40 yr]). Overall, 27 unplanned outcomes occurred (2.1%). The risk of unplanned outcomes did not appear to be different between procedures performed by a trainee with faculty oversight and those performed by a faculty member alone. Patients with multiple same-day procedures were more likely to have unplanned outcomes (21 of 27 [78%], P = 0.004) than were patients who had flexible bronchoscopy alone. The relative risk (RR) of having an unplanned outcome was not different from flexible bronchoscopy alone in the subset of patients with multiple procedures coordinated through our multidisciplinary aerodigestive clinic (RR 0.7; 95% CI, 0.1-3.4). The risk of unplanned events was significantly elevated in children with coordinated procedures scheduled outside the aerodigestive group (RR, 5.8; 95% CI, 2.4-14.5). Ten patients (<1%) were readmitted or seen urgently within 1 week; three of these unplanned outcomes were attributed to complications of the bronchoscopy. CONCLUSIONS: An EMR system may be used to track procedural outcomes. Unplanned outcomes after flexible bronchoscopy were infrequent at our institution. Children who underwent multiple procedures had unplanned outcomes more often; however, the subset of children who underwent coordinated procedures through our multidisciplinary aerodigestive clinic did not demonstrate this increased risk. PMID- 26816222 TI - Visual and non-visual motion information processing during pursuit eye tracking in schizophrenia and bipolar disorder. AB - Despite many reports on visual processing deficits in psychotic disorders, studies are needed on the integration of visual and non-visual components of eye movement control to improve the understanding of sensorimotor information processing in these disorders. Non-visual inputs to eye movement control include prediction of future target velocity from extrapolation of past visual target movement and anticipation of future target movements. It is unclear whether non visual input is impaired in patients with schizophrenia. We recorded smooth pursuit eye movements in 21 patients with schizophrenia spectrum disorder, 22 patients with bipolar disorder, and 24 controls. In a foveo-fugal ramp task, the target was either continuously visible or was blanked during movement. We determined peak gain (measuring overall performance), initial eye acceleration (measuring visually driven pursuit), deceleration after target extinction (measuring prediction), eye velocity drifts before onset of target visibility (measuring anticipation), and residual gain during blanking intervals (measuring anticipation and prediction). In both patient groups, initial eye acceleration was decreased and the ability to adjust eye acceleration to increasing target acceleration was impaired. In contrast, neither deceleration nor eye drift velocity was reduced in patients, implying unimpaired non-visual contributions to pursuit drive. Disturbances of eye movement control in psychotic disorders appear to be a consequence of deficits in sensorimotor transformation rather than a pure failure in adding cognitive contributions to pursuit drive in higher-order cortical circuits. More generally, this deficit might reflect a fundamental imbalance between processing external input and acting according to internal preferences. PMID- 26816224 TI - Rib stabilization: lessons learned. AB - INTRODUCTION: The management of rib fractures and flail chest has changed considerably over the past century, and recently there has been a renewed interest in operative rib stabilization for these injuries. Despite numerous reports suggesting improved outcomes with rib stabilization, there are not well defined indications and the approach remains somewhat controversial. MATERIALS AND METHODS: The authors reflect on their experience of performing rib stabilization in over 100 patients with rib fractures and flail chest. CONCLUSION: The authors offer their opinions on this operation with respect to rationale, indications, timing, technique, and postoperative care. PMID- 26816223 TI - Sensitivity to Change and Minimal Important Differences of the LupusQoL in Patients With Systemic Lupus Erythematosus. AB - OBJECTIVE: As a health-related quality of life (HRQOL) measure, the LupusQoL is a reliable and valid measure for adults with systemic lupus erythematosus (SLE). This study evaluates the responsiveness and minimal important differences (MIDs) for the 8 LupusQoL domains. METHODS: Patients experiencing a flare were recruited from 9 UK centers. At each of the 10 monthly visits, HRQOL (LupusQoL, Short Form 36 health survey [SF-36]), global rating of change (GRC), and disease activity using the British Isles Lupus Assessment Group 2004 index were assessed. The responsiveness of the LupusQoL and the SF-36 was evaluated primarily when patients reported an improvement or deterioration on the GRC scale and additionally with changes in physician-reported disease activity. MIDs were estimated as mean changes when minimal change was reported on the GRC scale. RESULTS: A total of 101 patients were recruited. For all LupusQoL domains, mean HRQOL worsened when patients reported deterioration and improved when patients reported an improvement in GRC; SF-36 domains showed comparable responsiveness. Improvement in some domains of the LupusQoL/SF-36 was observed with a decrease in disease activity, but when disease activity worsened, there was no significant change. LupusQoL MID estimates for deterioration ranged from -2.4 to -8.7, and for improvement from 3.5 to 7.3; for the SF-36, the same MID estimates were -2.0 to -11.1 and 2.8 to 10.9, respectively. CONCLUSION: All LupusQoL domains are sensitive to change with patient-reported deterioration or improvement in health status. For disease activity, some LupusQoL domains showed responsiveness when there was improvement but none for deterioration. LupusQoL items were derived from SLE patients and provide the advantage of disease-specific domains, important to the patients, not captured by the SF-36. PMID- 26816225 TI - Assessment of cardiac injury in patients with blunt chest trauma. AB - BACKGROUND: There has been difficulty in the appropriate determination of blunt cardiac injury (BCI) related to blunt thoracic trauma (BTT). The aim of this study is to assess BCI and the effectiveness of diagnostic tests in BTT in patients admitted to the emergency department (ED). METHODS: Eighty-eight patients with suspected myocardial injury in BTT were enrolled. The diagnostic criteria for BCI were: elevation of troponin I, arrhythmia requiring treatment, unexplained low voltage on electrocardiography (ECG), unexplained hypotension requiring vasopressor, cardiogenic shock requiring inotropes, and transthoracic echocardiographic (TTE) findings suggestive of BCI. Patients with arrhythmia in the medical history, congestive heart failure, ischemic heart disease, history of cardiac surgery, and those <16 years of age were excluded. RESULTS: The BCI rate was 25% in thoracic injuries. The sensitivity and specificity of troponin I, creatine kinase-MB fraction (CK-MB)/creatine kinase (CK) ratio, ECG, and CK-MB/CK ratio plus ECG were 68% and 100%, 50% and 53%, 54.5% and 72%, and 59% and 33%, respectively. Frequency of palpitation, initial CK-MB levels, initial heart rate, frequency of pulmonary contusion, abnormal ECG, and mortality rate were significantly higher in patients with BCI compared with patients without BCI. Pulmonary contusion, accompanying palpitation, Glasgow coma scale (GCS) <=13, and abnormal ECG findings were important independent parameters increasing the likelihood of BCI on univariate analysis comparing patients with and without BCI. CONCLUSION: Indicators such as cardiac enzymes and ECG have low sensitivity and specificity when used alone. The reliability of ECG in the diagnosis of BCI decreases in the later hours of trauma. PMID- 26816226 TI - The impact of trauma mechanism on outcome: a follow-up study on health-related quality of life after major trauma. AB - OBJECTIVES: To relate the trauma mechanism in a trauma population to health related quality of life outcomes and mortality rates. METHODS: A consecutive series of patients (>15 years old) with major injuries [Injury Severity Score (ISS) >=10] treated during a 2-year period at a general hospital in a city area were included (n = 458). Baseline data were collected from medical records, and patients were followed up 12 months post injury. Outcome was measured by health related quality of life (HRQoL) according to the SF-36 and musculoskeletal function according to the short musculoskeletal function assessment (SMFA). Mortality rates were collected during 7 years. RESULTS: Of all patients, 86.9% had an unintentional injury, 4.4% had a self-inflicted injury, and 8.7% had been assaulted. The mortality rate during the acute phase and at 7 years post trauma did not differ between the groups with different trauma mechanisms. At 12 months, patients with unintentional injuries and assault victims had SF-36 ratings comparable to the general population, while patients with self-inflicted injuries had worse ratings in all SF-36 domains except physical function and general health. There were no differences between the groups regarding SMFA results. CONCLUSION: Even though the follow-up rate was only 53%, this study showed that, at 12 months, patients with self-inflicted injuries had significantly lower HRQoL ratings. There was no difference in mortality with regard to trauma mechanism. Cooperation between emergency service and psychiatric care early in the acute phase could provide a golden opportunity to reach this patient group. PMID- 26816227 TI - Surface proteins and osteoblast markers: characterization of human adipose tissue derived osteogenic cells. AB - INTRODUCTION: In adipose tissue-derived osteogenic cells (ADOC), osteoblast markers and surface proteins were determined and compared with osteoblasts harvested from cancellous bone (OB). METHOD: Osteocalcin (OC), core binding factor 1 (CBFA1), collagen type 1 (Coll1), alkaline phosphatase (ALP), nucleostemin (NS), and surface proteins CD 10, CD44, CD 59 and CD 105 were analyzed using RT-PCR, immunofluorescence and Western blot. RESULTS: Osteocalcin expression was more distinct in OB than in ADOC, but the other markers and surface proteins showed no differences. CONCLUSION: These data support the use of adipose tissue for future regenerative medicine; however, further studies are necessary to establish the role of long-term differentiation. PMID- 26816228 TI - Emergency decompressive craniectomy for trauma patients with Glasgow Coma Scale of 3 and bilateral fixed dilated pupils. AB - BACKGROUND: Trauma patients with Glasgow Coma Scale (GCS) of 3 and bilateral fixed dilated pupils (BFDP) usually have dismal outcome, and neurosurgeons are less likely to treat such patients aggressively. In this work, the authors assessed whether emergency decompressive craniectomy (EDC) can change the poor outcome of these patients. METHODS: We reviewed all patients with GCS of 3 and BFDP admitted to our neurosurgical unit from January 2004 to January 2008. Injury data, prehospital times, findings on brain computed tomography (CT) scan, procedures, and outcomes were recorded. RESULTS: During this period, 21 patients were admitted with GCS of 3 and BFDP following traumatic brain injury (TBI). Brain CT scan showed diffuse brain edema in 17 patients (81%), and in 13 patients (62%) it showed different types of intracranial hemorrhage. All patients received conservative medical treatment. Urgent decompressive bifrontal craniectomy was performed in five patients at a mean of 4.6 h (range 2-6 h) from time of injury. Intracranial pressure (ICP) was recorded hourly by intraparenchymal sensor (Codman, Johnson & Johnson). Although decompressive craniectomy was effective in controlling ICP, all patients with GCS of 3 and BFDP died within 30 days of trauma. CONCLUSIONS: Despite control of ICP following emergency decompressive craniectomy in patients with severe TBI, GCS of 3, and BFDP, this did not change the dismal outcome of these patients; on the contrary, it may increase the suffering for patients and their families and add unnecessary medical burden. We propose that these patients have irreversible severe brain insult. PMID- 26816229 TI - Hoffa fracture: fixation using headless compression screws. AB - INTRODUCTION: Hoffa fractures are uni- or bicondylar fractures of the distal femur in a coronal tangential plane. CASE PRESENTATION: We report the case of an isolated, low energy, closed, displaced, lateral femoral condyle Hoffa fracture in a 54 year old Caucasian man. This was treated by open reduction and internal fixation using two headless compression screws. At 1 year review the patient was pain free, the fracture had radiographically united and there was a range of movement to his knee of 0 degrees -100 degrees . DISCUSSION: Traditional methods of fixation for Hoffa fractures have led either to the application of complicated constructs attempting to achieve stability, or to large articular surface defects created whilst countersinking headed lag screws. Both have negative implications for the patient. We describe a novel method, not previously described in the literature, using screws in a posterior to anterior direction. This provides compression perpendicular to the fracture site whilst protecting against shear and torsional forces, thereby providing more stable fixation. Furthermore, our method allows for a minimally invasive approach and uses headless compression screws, which reduces the chance of damage to the articular surface and is, therefore, less physiologically invasive. PMID- 26816230 TI - Putrid infectious pubic osteitis: case report and review of the literature on the differential diagnosis and treatment of infectious pubic osteitis and inflammatory pubic osteitis. AB - INTRODUCTION: The differential diagnosis of osteolytic, destructive, and inflammatory processes around the symphysis, the os pubis, and the ramus ossis pubis includes infectious osteitis pubis, inflammatory osteitis pubis, posttraumatic benign pubic osteolyses in elderly women, and malignant neoplasia. Accurate diagnosis can be a challenge and requires a methodical approach and the use of a variety of diagnostic measures. MATERIALS: A case study of an 83-year old female suffering from infectious pubis osteitis sheds light on the differential diagnosis of these conditions, particularly the distinction between infectious pubic osteitis and inflammatory pubis osteitis. In addition to the diagnostic indicators and methodologies, differential treatments are considered and a review of current literature on the topic is presented. PMID- 26816231 TI - Simultaneous dislocation of the interphalangeal and metacarpophalangeal joints of the thumb. AB - Simultaneous dislocation of the interphalangeal and metacarpophalangeal joints of the thumb is an extremely rare injury, the management of which is controversial. We advocate closed reduction followed by early mobilisation in order to achieve optimal functional results. PMID- 26816232 TI - Intestinal derotation in emergency surgery. AB - Intestinal derotation (ID) is a rarely used surgical technique which allows elegant and effective surgical access to the superior mesenteric axis and third and fourth portion of the duodenum. ID proves an extremely useful technique especially in the emergency setting when access to the "surgical soul" is needed. To master this technique the surgeon has to become familiar with the anatomical landmarks of that area along with the embryological background. PMID- 26816233 TI - Acute aortic valve insufficiency following blunt chest trauma. AB - Acute aortic valve insufficiency caused by laceration of the aortic valve cusp after blunt chest trauma is a rare condition. We report herein on a case of a 40 year-old patient who initially presented with cardiac tamponade and cardiac arrest after a traffic accident. The patient ultimately received aortic valve repair to treat acute aortic regurgitation due to multiple perforations on a single cusp, visualized on multidetector chest computed tomography scan (128 channels). PMID- 26816234 TI - Immunomodulation in Middle-Aged Humans Via the Ingestion of Physta(r) Standardized Root Water Extract of Eurycoma longifolia Jack--A Randomized, Double Blind, Placebo-Controlled, Parallel Study. AB - This study was aimed to investigate the capacity of a standardized root water extract of Eurycoma longifolia (Tongkat Ali, TA), Physta(r) to modulate human immunity in a middle-aged Japanese population. This randomized, double-blind, placebo-controlled, parallel study was conducted for 4 weeks. Eighty-four of 126 subjects had relatively lower scores according to Scoring of Immunological Vigor (SIV) screening. Subjects were instructed to ingest either 200 mg/day of TA or rice powder as a placebo for 4 weeks [TA and Placebo (P) groups] and to visit a clinic in Tokyo twice (weeks 0 and 4). SIV, immunological grade, immunological age, and other immune parameters were measured. Eighty-three subjects completed the study; 40 in the TA group and 41 in the P group were statistically analyzed, whereas two were excluded from the analyses. At week 4, the SIV and immunological grade were significantly higher in the TA group than those in P group (p < 0.05). The numbers of total, naive, and CD4(+) T cells were also higher in the TA group than those in P group (p < 0.05). No severe adverse events were observed. The results suggest that ingestion of the root water extract of TA (Physta(r)) enhances comprehensive immunity in both middle-aged men and women. This study is registered in UMIN-CTR (UMIN000011753). PMID- 26816235 TI - Comment on: Malek MH et al. Muscle and Nerve 44: 432-438; 2011. PMID- 26816236 TI - Introduction to the 5th focus-on issue devoted to disaster and military surgery. PMID- 26816237 TI - Challenges in the training of military surgeons: experiences from Dutch combat operations in southern Afghanistan. AB - BACKGROUND: To improve care for battle casualties, we analyzed the surgical workload during the Dutch deployment to Uruzgan, Afghanistan. This surgical workload was compared with the resident surgical training and the pre-deployment medical specialist program. METHODS: Patient data from the trauma registry (2006 2010) at the Dutch Role 2 Medical Treatment Facility (MTF) were analyzed. The case logs of chief residents (n = 15) from the general surgery training program in the Netherlands were used for comparison. RESULTS: The trauma registry query yielded 2,736 casualties, among whom 60 % (1,635/2,736) were classified as disease non-battle casualties and 40 % (1,101/2,736) as battle casualties. During the study period, 1,427 casualties (336 pediatric cases) required 2,319 surgical procedures. Each graduating chief resident handled an average of 1,444 cases, including 165 laparotomies, 19 major vessel repairs, 28 amputations, and 153 fracture stabilizations, during their residency. Residents had limited exposure to injuries requiring a thoracotomy, craniotomy, nephrectomy, IVC repair, or external genital trauma. CONCLUSIONS: The injuries treated at the Dutch Role 2 MTF were often severe, and exposure to pediatric cases was much higher than reported for other combat hospitals in Iraq and in Afghanistan. The current civilian resident training does not equip the trainees with the minimally required competences of a fully trained military surgeon. The recognition in the Netherlands of military surgery as a subspecialty within general (trauma) surgery, with a formal training curriculum, should be considered. The introduction of a North Atlantic Treaty Organization Military (and Disaster) Surgery standard may facilitate the achievement of this aim. PMID- 26816238 TI - Development and evaluation of a new simulation model for interactive training of the medical response to major incidents and disasters. AB - BACKGROUND AND AIMS: The need for and benefit of simulation models for interactive training of the response to major incidents and disasters has been increasingly recognized during recent years. One of the advantages with such models is that all components of the chain of response can be trained simultaneously. This includes the important communication/coordination between different units, which has been reported as the most common cause of failure. Very few of the presently available simulation models have been suitable for the simultaneous training of decision-making on all levels of the response. In this study, a new simulation model, originally developed for the scientific evaluation of methodology, was adapted to and developed for the postgraduate courses in Medical Response to Major Incidents (MRMI) organized under the auspices of the European Society for Trauma and Emergency Surgery (ESTES). The aim of the present study was to describe this development process, the model it resulted in, and the evaluation of this model. METHODS: The simulation model was based on casualty cards giving all information normally available for the triage and primary management of traumatized patients. The condition of the patients could be changed by the instructor according to the time passed since the time of injury and treatments performed. Priority of the casualties as well as given treatments could be indicated on the cards by movable markers, which also gave the time required for every treatment. The exercises were run with real consumption of time and resources for all measures performed. The magnetized cards were moved by the trainees through the scene, through the transport lines, and through the hospitals where all functions were trained. For every patient was given the definitive diagnosis and the times within certain treatments had to be done to avoid preventable mortality and complications, which could be related to trauma scores. RESULTS: The methodology was tested in nine MRMI courses with a total of 470 participants. Based on continuous evaluations and accumulated experience, the setup of the simulation was step-wise adjusted to the present model, including also collaborating agencies such as fire and rescue services as well as the police, both on-scene and on superior command levels. The accuracy of the simulation cards for this purpose was evaluated as "very good" by 63 % of the trainees and as "good" by 33 %, the highest two of the six given alternatives. The participants' ranking of the extent that the course increased their competencies related to the given objectives on a 1-5 scale for prehospital staff had an average value of 4.25 +/- 0.77 and that for hospital staff had an average value of 4.25 +/- 0.72. The accuracy of the course for the training of major incident response on a 1-5 scale by prehospital staff was evaluated as 4.35 +/- 0.73 and that by hospital staff as 4.30 +/- 0.74. CONCLUSIONS: The simulation system tested in this study could, with adjustments based on accumulated experience and evaluations, be developed into a tool for the training of major incident response meeting the specific demands on such training based on recent experiences from major incidents and disasters. Experienced trainees in several courses evaluated the methodology to be accurate for this training, markedly increasing their perceived knowledge and skills in fields of importance for a successful outcome of the response to a major incident. PMID- 26816239 TI - Pitfalls to avoid in the medical management of mass casualty incidents following terrorist bombings: the hospital perspective. AB - BACKGROUND: The unique patterns of injury following explosions together with the involvement of numerous physicians, most of whom are not experienced in trauma, may create problems in the medical management of mass casualty incidents. METHODS: Four hundred patient files admitted in 19 mass casualty events following bombing incidents were reviewed and possible areas which could impact survival were defined. RESULTS: Forty-nine (9.3 %) patients had an Injury Severity Score >=16. Of 205 patients in whom triage decisions were available, 5 of 25 severely injured patients were undertriaged by the triage officers at the door of the hospital. Following primary evaluation inside the emergency department critical injuries in two patients were missed due to distracting, less serious injuries. Of 68 (16.1 %) patients who were operated, 28 were in need of either immediate, urgent or high-priority operations. Except for neurosurgical cases which needed to be transferred to other hospitals, there was no delay in surgery. One patient underwent negative laparotomy. There were 15 in-hospital deaths, 6 of which were deemed as either anticipated or unanticipated mortality with possibility for improvement. CONCLUSION: Medical management should be evaluated following MCIs as this may illustrate possible problems which many need to be addressed in contingency planning. PMID- 26816240 TI - Abdominal blast injuries: different patterns, severity, management, and prognosis according to the main mechanism of injury. AB - PURPOSE: To review the frequency, different patterns, anatomic severity, management, and prognosis of abdominal injuries in survivors of explosions, according to the main mechanism of injury. METHODS: A MEDLINE search was conducted from January 1982 to August 2013, including the following MeSH terms: blast injuries, abdominal injuries. EMBASE was also searched, with the same entries. Abdominal blast injuries (ABIs) have been defined as injuries resulting not only from the effects of the overpressure on abdominal organs, but also from the multimechanistic effects and projectile fragments resulting from the blast. Special emphasis was placed on the detailed assessment of ABIs in patients admitted to GMUGH (Gregorio Maranon University General Hospital) after the Madrid 2004 terrorist bombings, and in patients admitted to HYMC (Hillel Yaffe Medical Centre) in Hadera (Israel) following several bombing episodes. The anatomic severity of injuries was assessed by the abdominal component of the AIS, and the overall anatomic severity of casualties was assessed by means of the NISS. RESULTS: Abdominal injuries are not common in survivors of terrorist explosions, although they are a frequent finding in those immediately killed. Primary and tertiary blast injuries have predominated in survivors from explosions in enclosed spaces reported outside of Israel. In contrast, secondary blast injuries causing fragmentation wounds were predominant in suicide bombings in open and/or semi-confined spaces, mainly in Israel, and also in military conflicts. Multiple perforations of the ileum seem to be the most common primary blast injury to the bowel, but delayed bowel perforations are rare. Secondary blast injuries carry the highest anatomic severity and mortality rate. Most of the deaths assessed occurred early, with hemorrhagic shock from penetrating fragments as the main contributing factor. The negative laparotomy rate has been very variable, with higher rates reported, in general, from civilian hospitals attending a large number of casualties. CONCLUSIONS: The pattern, severity, management, and prognosis of ABI vary considerably, in accordance with the main mechanism of injury. PMID- 26816241 TI - Wounds of war in the civilian sector: principles of treatment and pitfalls to avoid. AB - INTRODUCTION: Terror attacks with explosive devices or mass shootings have introduced a new pattern of injuries into the civilian sector. The aim of this short review on the treatment principles for so-called penetrating war wounds is to remind surgeons who are not normally confronted with them of some basic rules to follow and pitfalls to avoid. MATERIALS AND METHODS: This review article is based on literature research of the National Library of Medicine and the National Institutes of Health MEDLINE database using PubMed, as well as updated books on war surgery and the author's own experience of war zones. RESULTS AND DISCUSSION: Principles of treatment of penetrating war injuries to the head, neck, and torso are all based on damage control surgery focusing on hemorrhage and contamination control and early restoration of the deranged physiology. For injuries to the extremities, differences in treatment principles between low- and high-energy wounds are more important, although initial treatment is also focused on hemorrhage control. The surgical treatment should be based on thorough wound examination and debridement as well as fracture stabilization when required. CONCLUSION: Certain knowledge of the treatment of war wounds is necessary in all civilian hospitals that receive patients injured in terror attacks. PMID- 26816243 TI - Proper coding of the Abbreviated Injury Scale: can clinical parameters help as surrogates in estimating blood loss? AB - PURPOSE: The Abbreviated Injury Scale (AIS) requires the estimation of the lost blood volume for some severity assignments. This study aimed to develop a rule of thumb for facilitating AIS coding by using objective clinical parameters as surrogate markers of blood loss. METHODS: Using the example of pelvic ring fractures, a retrospective analysis of TraumaRegister DGU((r)) data from 2002 to 2011 was performed. As potential surrogate markers of blood loss, we recorded the hemoglobin (Hb) level, systolic blood pressure (SBP), base excess (BE), Quick's value, units of packed red blood cells (PRBCs) transfused before intensive care unit (ICU) admission, and mortality within 24 h. RESULTS: We identified 11,574 patients with pelvic ring fractures (Tile/OTA classification: 39 % type A, 40 % type B, 21 % type C). Type C fractures were 73.1 % AISpelvis 4 and 26.9 % AISpelvis 5. Type B fractures were 47 % AISpelvis 3, 47 % AISpelvis 4, and 6 % AISpelvis 5. In type C fractures, cut-off values of <7 g/dL Hb, <90 mmHg SBP, <-9 mmol/L BE, <35 % Quick's value, >15 units PRBCs, and death within 24 h had a positive predictive value of 47 % and a sensitivity of 62 % for AISpelvis 5. In type B fractures, these cut-off values had poor sensitivity (48 %) and positive predictive value (11 %) for AISpelvis 5. CONCLUSIONS: We failed to develop a rule of thumb for facilitating a proper future AIS coding using the example of pelvic ring fractures. The estimation of blood loss for severity assignment still remains a noteworthy weakness in the AIS coding of traumatic injuries. PMID- 26816244 TI - The role of decompressive craniectomy in children with severe traumatic brain injury. AB - OBJECTIVE: Severe traumatic brain injury (TBI) remains the leading cause of death in children. The present study analyses the outcome of children after severe TBI treated by decompressive craniectomy (DC) due to elevated intracranial pressure (ICP) in a single centre. METHODS: Fifty-six consecutive children (age < 16 years) were treated for severe TBI at our institution between 2001 and 2011. For study purposes, children with severe generalized traumatic brain swelling without concomitant mass lesion were further analysed. Descriptive statistics were used to report clinical conditions as well as outcome measurements after conservative treatment only in comparison to secondary decompressive craniectomy. RESULTS: Of 56 children, a total of eight children presented with generalized and progressive traumatic brain swelling and impending brain herniation. Four children were treated conservatively following standardized local protocol for anti-oedematous management, with ICP amenable to intensified therapy. Four children required decompressive surgery due to progressive oedema refractory to intensified conservative management. Children receiving secondary DC had a longer stay in the intensive care unit as well as a longer average time of assisted ventilation compared to children treated conservatively. Concomitant injuries were more severe in the DC subgroup. Yet, Glasgow Outcome Scale was equally distributed in both groups. CONCLUSION: In children with refractory ICP conditions due to severe TBI, decompressive surgery might lead to a similar favourable outcome compared to children in whom ICP can be controlled only by conservative management. Timing of surgery depends on the neurological deterioration of the patients and a continuous ICP monitoring. PMID- 26816245 TI - Reamed versus unreamed nail in the treatment of tibia shaft fractures. AB - PURPOSE: The aim of the prospective randomized study was to compare the results of the treatment of tibia shaft fractures (TSF) by reamed or unreamed intramedullar nail. METHODS: There were 103 patients with 104 TSF enrolled in the study within the period from December 2005 to June 2010. Seven patients were excluded from the study. Factors of injury severity, course of surgery and hospitalization, and incidence of early and delayed complications were recorded. X-ray was performed every 4 weeks until the fracture was healed. Functional results were evaluated at least 1 year after the surgery. Closed fractures were classified according to Tscherne classification and the open ones according to Gustilo classification. RESULTS: Forty-eight patients with 49 TSF were treated by unreamed tibial nail. There were 15 women and 33 men in this group. Injury severity score (ISS) ranged from 4 to 25 (o 6.63). There were 45 closed fractures (0 16; I 22; II 7) and four open fractures (I 2; II 1; IIIA 1). In the reamed nail group there were 48 TSF. ISS ranged from 4 to 18 (o 6.13). There were 35 closed (0 17; I 13; II 5) and 13 open (I 5; II 5; IIIA 3) fractures in this group. The time of operation was on average 15 min shorter in the unreamed nail group. X-ray healing was the same in both groups (18.12 versus 17.92 weeks). We had four patients in the unreamed nail group and six patients in the reamed nail group with delayed healing (28-44 weeks). We recorded no infection, loss of reduction or re-operation in both groups. Follow-up of functional results was 90 %. CONCLUSIONS: There was no statistically significant difference in clinical and functional results between the groups. We suggest that both methods are comparable. PMID- 26816246 TI - Clinical and functional outcomes of internal fixation with intertrochanteric antegrade nail in older patients with proximal extracapsular femoral fractures. AB - PURPOSE: The intertrochanteric Trigen Intertan((r)) nail (Smith & Nephew, Memphis, TN) is a popular fixation device for proximal extracapsular femoral fractures (PEFFs). We evaluated clinical and functional outcomes in patients with PEFFs treated with Trigen Intertan((r)) nail. METHODS: In a single-site, prospective observational study, clinical and functional parameters were recorded for all patients admitted to the Emergency Department with PEFFs from June 2008 through June 2011. Patients with severe cognitive impairment, severe disability, neoplastic pathological fractures, or suffering from terminal illnesses were not eligible for the study. Fractures were classified according to the AO/OTA classification system. Preoperative physical fitness was assessed via the American Association of Anaesthetists (ASA) score. The Barthel index was used to quantify the level of physical function before fracture and at follow-up. RESULTS: One-hundred thirty-five patients with PEFFs were eligible for inclusion during the 3-year survey (mean age 83.2 +/- 9.5 years; 82 % females). Fracture type distribution was as follows: A1.1 = 18 %, A1.2 = 7 %, A1.3 = 5 %, A2.1 = 44 %, A2.2 = 21 %, A2.3 = 5 %. All patients were treated with Trigen Intertan((r)) nail. Two patients experienced a fracture of the femoral shaft during the insertion of a long nail for an A2.3 fracture. Weight-bearing was allowed between the third and tenth postoperative day depending on pain tolerance and general conditions. No loss of reduction, collapse of the femoral neck, nonunion or fixation failure were observed. Two patients died within 10 days postoperatively, and nine within 6 months after surgery. Functional status 1 month after surgery was lower than pre-fractural levels, and improved over follow-up. At 6 months, functional status was comparable to the pre-fractural level. CONCLUSIONS: Trigen Intertan((r)) produces highly satisfactory clinical and functional results in older patients with PEFFs. Complete functional recovery is obtained on average 6 months after surgery. PMID- 26816247 TI - Surgical stabilization of flail chest: the impact on postoperative pulmonary function. AB - OBJECTIVES: Flail chest results in significant morbidity. Controversies continue regarding the optimal management of flail chest. No clear guidelines exist for surgical stabilization. Our aim was to examine the association of bedside spirometry values with operative stabilization of flail chest. METHODS: IRB approval was obtained to identify patients with flail chest who underwent surgical stabilization between August 2009 and May 2011. At our institution, all rib fracture patients underwent routine measurement of their forced vital capacity (FVC) using bedside spirometry. Formal pulmonary function tests were also obtained postoperatively and at three months in patients undergoing stabilization. Both the Synthes and Acute Innovations plating systems were utilized. Data is presented as median (range) or (percentage). RESULTS: Twenty patients (13 male: 65 %) with median age of 60 years (30-83) had a median of four ribs (2-9) in the flail segment. The median Injury Severity Score was 17 (9-41) and the median Trauma and Injury Severity Score was 0.96 (0.04-0.99). Preoperative pneumonia was identified in four patients (20 %) and intubation was required in seven (35 %). Median time from injury to stabilization was four days (1-33). The median number of plates inserted was five (3-11). Postoperative median FVC (1.8 L, range 1.3-4 L) improved significantly as compared to preoperative median value (1 L, range 0.5-2.1 L) (p = 0.003). This improvement continued during the follow-up period at three months (0.9 L, range 0.1-3.0) (p = 0.006). There were three deaths (15 %), none of which were related to the procedure. Subsequent tracheostomy was required in three patients (15 %). The mean hospital stay and ventilator days after stabilization were nine days and three days, respectively. Mean follow-up was 5.6 +/- 4.6 months. CONCLUSION: Operative stabilization of flail chest improved pulmonary function compared with preoperative results. This improvement was sustained at three months follow-up. PMID- 26816248 TI - ESTES News 4.2014. PMID- 26816249 TI - Design and Synthesis of Core-Shell-Shell Upconversion Nanoparticles for NIR Induced Drug Release, Photodynamic Therapy, and Cell Imaging. AB - Novel core-shell-shell structured nanoparticles 75 nm in diameter with all-in-one "smart" functional capabilities for simultaneous photoresponsive drug release, photodynamic therapy, and cell imaging are designed and prepared. These nanoparticles consist of an upconversion (UC) emission core, a photosensitizer embodied silica sandwich shell, and a beta-cyclodextrin (beta-CD) gated mesoporous silica outmost shell with drugs (Rhodamine B as a model) loaded inside. We show in this proof-of-concept demonstration that, under 980 nm near infrared irradiation, UC 540 nm green light emissions were emitted for cell imaging, and 660 nm red light emissions were excited for activating photosensitizers to generate singlet oxygen, which could be exploited directly to kill cancer cells and simultaneously dissociate beta-CD gatekeeper to release drugs. The preliminary results reported here will shed new light on the future design and applications of multifunctional platforms for cancer therapy and diagnostic. PMID- 26816251 TI - Pelvic and acetabular fractures. PMID- 26816250 TI - miR-105/Runx2 axis mediates FGF2-induced ADAMTS expression in osteoarthritis cartilage. AB - Fibroblast growth factor 2 (FGF2) plays an important role in the development of osteoarthritis (OA) through the regulation of cartilage degradation. However, the molecular mechanism underlying FGF2-induced OA is poorly characterized. MicroRNAs (miRNAs) maintain cartilage homeostasis. To examine whether FGF2 regulates OA through the modulation of miRNA, we screened potential miRNA molecules that could be regulated through FGF2 using microarray analysis. The results showed that microRNA-105 (miR-105) was significantly downregulated in chondrocytes stimulated with FGF2. Runt-related transcription factor 2 (Runx2), a key transcription factor involved in OA, has been identified as a novel potential target of miR 105. FGF2 suppressed miR-105 expression through the recruitment of the subunit of the nuclear factor kappa B transcription complex p65 to the miR-105 promoter. The knockdown of Runx2 mimicked the effect of miR-105 and abolished the ability of miR-105 to regulate the expression of a disintegrin-like and metalloproteinase with thrombospondin 4 (ADAMTS4), ADAMTS5, ADAMTS7 and ADAMTS12, both of which are responsible for the degradation of collagen 2A1 (COL2A1) and aggrecan (ACAN). miR 105 is also required for FGF2/p65-induced Runx2 activation and ADAMTS expression. Moreover, miR-105 expression was downregulated in OA patients and inversely correlated with the expression of Runx2, ADAMTS7 and ADAMTS12, which were upregulated in OA patients. These data highlight that the FGF2/p65/miR 105/Runx2/ADAMTS axis might play an important role in OA pathogenesis and that miR-105 might be a potential diagnostic target and useful strategy for OA treatment. KEY MESSAGE: Runx2 was identified as a novel direct target of miR-105. FGF2 inhibits miR-105 transcription through recruitment of p65 to miR-105 promoter. p65/miR-105 is essential for FGF2-mediated Runx2 and ADAMTS upregulation. miR-105 is downregulated in OA and inversely correlated with Runx2 expression. PMID- 26816252 TI - The management of complex acetabular fractures in the elderly with fracture fixation and primary total hip replacement. AB - Osteoporosis and associated fragility fractures are an increasing problem across the developed world. The elderly osteoporotic acetabular fracture presents a difficult problem due to high failure rates and poor outcomes. Standard management may or may not include fracture fixation, but generally includes a period of protected weight bearing, even if total hip replacement has been performed. We present a series of 12 cases of complex osteoporotic acetabular fractures in elderly patients, managed successfully using primary fracture fixation and total hip replacement with trabecular metal technology. Immediate weight bearing was allowed in all cases, few complications have been seen, and no component migration has been identified in any case. PMID- 26816253 TI - Management of traumatic spinopelvic dissociations: review of the literature. AB - PURPOSE: Spinopelvic dissociation is a rare high-energy injury pattern in adults associated with high morbidity and an increased rate of neurological deficits. The purpose of this article is the conception of fracture type-associated treatment recommendations. METHODS: This article is based on our own experience with spinopelvic dissociations and a review of the current literature. RESULTS: Bilateral vertical plus an optional transverse fracture component configures spinopelvic dissociations as "U"- or "H"-shaped, with the result of a spinopelvic dissociation. "Y"-, "T"- or "II"-shaped fractures do not necessarily belong to this entity but can be subsumed to this entity in a wider sense. The surgical treatment of these injuries remains challenging. Initial haemodynamic stabilisation represents the main goal of primary care until definitive treatment can be performed. Anatomical reduction is demanding and even more complex in fracture areas with large comminution. Surgical treatment options depend on the fracture type, including transsacral screws, sacral banding and spinopelvic fixation, plus combinations of these procedures. CONCLUSIONS: Spinopelvic dissociations remain highly complex injuries. "U"- and "H"-shaped fractures usually require triangular fixation, whereas "II"-, "Y"- and "T"-shaped fractures might be sufficiently stabilised with transsacral screws. PMID- 26816255 TI - Editorial Comment. PMID- 26816254 TI - Acute care surgery in the USA: the orthopaedic conflict. PMID- 26816256 TI - Evolution-based algorithm for the management of penetrating abdominal stab injury. AB - PURPOSE: As an increasing amount of penetrating abdominal stab injuries has been observed in the last few decades, it is important to evaluate the adequacy of the medical systems and surgical education and training to handle this type of injury. The aim of this study was to analyze the outcome of patients with penetrating abdominal stab injuries admitted to the Emergency Unit and to evaluate the effects of using a new treatment algorithm. METHODS: From January 2009 to April 2009, a standardized education and training system for the surgical team was implemented in order to improve the emergency medical care system. From April 2009 to April 2011, 106 patients with the diagnosis of a penetrating abdominal stab injury were prospectively included in the study. RESULTS: The cohort included 98 males and the mean age was 29.40 +/- 10.9 years. Eighty-two percent of the patients were managed conservatively, whereas 18 % underwent surgery. Based on the surgical outcomes of the patients, the rate of negative, non-therapeutic, and therapeutic laparotomies was 5, 11, and 84 %, respectively. No statistically significant difference between patients who did and did not receive surgery was observed with regards to blood pressure, temperature, hematocrit, hemoglobin, and C-reactive protein (CRP) values. However, a statistically significant difference was observed in the pulse rate, leukocyte, and neutrophil counts. The mortality and morbidity rates were 0.94 and 3.77 %, respectively. CONCLUSIONS: Selective non-operative management, which has been standardized in trauma centers, may be carefully utilized in order to treat penetrating abdominal stab wounds with caution in well-equipped medical centers with well-trained staff. PMID- 26816257 TI - Rectus sheath haematoma: are there prognostic risk factors of haemodynamic instability motivating an early operative treatment? AB - PURPOSE: Rectus sheath haematoma (RSH) is an uncommon condition caused by lesion of the superior or inferior epigastric arteries or their branches or by rupture of the rectus muscle. Treatment is usually supportive; however, if haemodynamic compromise develops, intravascular embolisation or surgery may be required. Furthermore, in some cases, bleeding may be so conspicuous that it can determine the patient's death before an adequate treatment is performed. We performed a retrospective study on 78 consecutive patients with the diagnosis of RSH admitted to the General Surgery Unit of our hospital between January 2000 and December 2010 in order to identify possible prognostic risk factors that could affect the operational approach before the onset of haemodynamic instability. METHODS: Demographic characteristics, patient history, laboratory and diagnostic imaging examinations were investigated. The variables considered were: gender, age, anti coagulation or anti-platelet therapy, trauma, international normalised ratio (INR) and bleeding time in the first 72 h of observation and concomitant diseases. The data were used for statistical analysis. RESULTS: Sixty patients received a conservative treatment, while 18 underwent operative treatment for haemodynamic instability (embolisation in 2 patients and surgery in 16 patients). Three of these 18 patients (17 %) died for consumption coagulopathy after surgery. None of the variables included in the univariate statistical analysis was significant (p = ns). CONCLUSION: Ultrasonography or computed tomography are the most common methods used to establish the diagnosis of RSH, so it is no longer a diagnostic dilemma. Most patients can be treated conservatively and an operative treatment is justified only in case of haemodynamic instability. Our retrospective study could not identify any prognostic risk factor of haemodynamic instability in RSH. We believe that only a close observation of the patients with RSH and "common sense" can prevent a possible fatal outcome. PMID- 26816258 TI - Perioperative management of laryngotracheobronchial injury: our experience in a level 1 trauma centre. AB - PURPOSE: Laryngotracheobronchial injuries (LTBI) are serious injuries because of their consequences in terms of ventilation, coupled with the severity of other injuries associated with them. We share our experience in managing these patients perioperatively in our level 1 trauma centre. METHODS: A retrospective analysis of the records of 30 patients with LTBI who presented at Jai Prakash Narayan Apex Trauma Center (JPNATC) from December 2007 to February 2011 was done. The demographics, mechanism of injury, clinical presentation, diagnostic modalities, anaesthetic management and outcome in these patients were reviewed. RESULTS: Intrathoracic location of the injury and Injury Severity Score (ISS) had a direct correlation with the outcome of the patients. The overall mortality was 6.7 %. CONCLUSION: Meticulous examination, details about the mechanism of injury, careful diagnostic evaluation, and skilful airway and surgical management are necessary for a better outcome in patients with airway injuries. A high degree of suspicion in occult injuries and liberal use of a fibreoptic bronchoscope aids diagnosis and management. Prompt airway management in the pre-hospital setting before transfer to a higher level trauma centre ensures better outcomes. PMID- 26816259 TI - Blind subxiphoid pericardiotomy to relieve critical acute hemopericardium: a final report. AB - PURPOSE: Percutaneous catheter drainage (PCD) has been considered a standard method of relieving acute cardiac tamponade. Although conventional subxiphoid pericardiotomy is useful even for clotted hemopericardium, it has been believed to be unsuitable for emergency treatment because it is a time-consuming procedure. We report our modified pericardiotomy technique that can be used for emergency management. METHODS: We designed a prospective observational study to evaluate blind subxiphoid pericardiotomy (BSP) for critical cardiac tamponade due to hemopericardium. Emergency patients (n = 148) with acute hemopericardium secondary to trauma (n = 12), acute aortic disease (n = 122), or cardiac rupture following acute myocardial infarction (n = 14) were the subjects. Early results were compared between the BSP group (n = 53) and the PCD group (n = 95). RESULTS: BSP was effective at relieving cardiac tamponade in all 53 cases, but PCD was ineffective in 12 cases (12.6 %, p = 0.008). Procedure-related complication rates of BSP and PCD were 0 and 16.8 %, respectively (p = 0.002). Survival rates for the BSP and PCD groups were 18.9 and 6.3 %, respectively (p = 0.018). Since 2005, when we discarded the restriction that only board-certified surgeons should perform BSP, acute care physicians (including trainees) have performed BSP for 22 patients without procedure-related complications. CONCLUSIONS: BSP was safe and effective for cardiac tamponade due to acute hemopericardium. Critical complications during PCD for hemopericardium could not be avoided in some cases because of clots in the pericardium. PMID- 26816261 TI - Message from the Secretary General. PMID- 26816260 TI - Intestinal obstruction due to bezoars: a retrospective clinical study. AB - PURPOSE: The purpose of this study was to compare the results of surgical procedures applied to rare intestinal obstruction cases due to bezoars and to identify effective factors for determining the type of surgical procedure to be applied. METHODS: The records of 62 patients who had received gastrointestinal surgical treatment due to bezoars were assessed retrospectively. The preoperative characteristics, perioperative findings and postoperative results of cases that had and had not undergone an enterotomy were compared RESULTS: The average patient age was 57.7 years (range, 26-84 years), and all patients had phytobezoars, except one. The most common location for bezoars was the jejunum (28 cases, 45.1 %). Sixteen cases (25.8 %) had multiple bezoars located in different parts of the gastrointestinal tract. While milking was applied to 26 cases (41.9 %) with small intestinal bezoars, an enterotomy was used to remove bezoars in 23 cases (37 %). More complications tended to be identified in patients who underwent an enterotomy; however, the difference was not significant (p = 0.553). CONCLUSIONS: The frequency of previous abdominal surgery in patients suffering from an intestinal obstruction due to bezoars causes diagnostic conflict. The location of bezoars in the small intestine should also be considered when deciding the surgical procedure, as well as the physical properties of the bezoars. Our opinion is that conducting the milking procedure should not be insisted on, and that an enterotomy should be conducted when necessary. PMID- 26816262 TI - VA-Index: Quantifying Assortativity Patterns in Networks with Multidimensional Nodal Attributes. AB - Network connections have been shown to be correlated with structural or external attributes of the network vertices in a variety of cases. Given the prevalence of this phenomenon network scientists have developed metrics to quantify its extent. In particular, the assortativity coefficient is used to capture the level of correlation between a single-dimensional attribute (categorical or scalar) of the network nodes and the observed connections, i.e., the edges. Nevertheless, in many cases a multi-dimensional, i.e., vector feature of the nodes is of interest. Similar attributes can describe complex behavioral patterns (e.g., mobility) of the network entities. To date little attention has been given to this setting and there has not been a general and formal treatment of this problem. In this study we develop a metric, the vector assortativity index (VA-index for short), based on network randomization and (empirical) statistical hypothesis testing that is able to quantify the assortativity patterns of a network with respect to a vector attribute. Our extensive experimental results on synthetic network data show that the VA-index outperforms a baseline extension of the assortativity coefficient, which has been used in the literature to cope with similar cases. Furthermore, the VA-index can be calibrated (in terms of parameters) fairly easy, while its benefits increase with the (co-)variance of the vector elements, where the baseline systematically over(under)estimate the true mixing patterns of the network. PMID- 26816263 TI - Comparison of fluid leakage across endotracheal tube cuffs using a three dimensional printed model of the human trachea. AB - The objective of this study was to compare fluid leakage across endotracheal tube cuffs using a three-dimensional (3D)-printed human tracheal model that anatomically simulates the human trachea. We made two models based on computed tomography data of the neck and chest. Using a Mallinckrodt Hi-LoTM (HL), ThinCuff((r)) (TC), and Mallinckrodt TaperGuardTM (TG), we sequentially measured the amount of fluid leakage across each endotracheal tube cuff after applying saline or viscous liquid above the cuff. The TG allowed significantly less leakage than the HL and TC with both saline and the viscous liquid. Our study, using a 3D-printed tracheal model, indicated that a conical-shaped endotracheal tube cuff significantly reduces fluid leakage across the cuff compared with conventional cylindrical-shaped cuffs made of polyurethane or polyvinylchloride, contrary to the results of a previous study using a solid cylindrical structure. PMID- 26816264 TI - Design, Synthesis, and Proticity Inclined Conformational Modulation in a Highly Fluorescent Bichromophoric Naphthalimide Derivative: Hint Directed from RICT Perspective. AB - The present study embodies design, in silico DNA interaction, synthesis of benzothiazole containing naphthalimide derivative, 2-(6-chlorobenzo[d]thiazol-2 yl)-1H-benzo[de] isoquinoline-1,3(2H)-dione (CBIQD) along with its systematic photophysics, solvatochromic behavior, and solvation dynamics using an experimental and theoretical spectroscopic approach. Steady-state dual emission and biexponential fluorescence decay reveals the formation of two different excited species. Ground- and excited-state optimized geometry and the potential energy curve obtained from DFT and TD-DFT calculation ascertained the existence of nonplanar and planar conformation. When the solvent polarity is changed from nonpolar to protic polar, the feebly emissive emission band highly intensifies probably due to the reversal of n, pi*-pi, pi* emissive state along with consequent modulation of their energy gap that is induced by H-bonding. Excluding nonpolar solvents, in all other solvents, the Stokes shift correlates linearly with orientation polarizability, whereas in water, the story remains intriguing. With photoexcitation, intermolecular H-bonding stimulates the pyramidalization tendency of imide "N" with subsequent conformational change of GS nonplanar geometry to a coplanar one through acceptor rehybridization generating a rehybridized intramolecular charge transfer (RICT) state that caused a dramatic fluorescence upsurge. This allosteric modulation is promoted by excited-state H bonding dynamics especially in strong H-bond donor water. A close interplay between preferential solvation and the proximity effect is evident in the emission behavior in a benzene (Bn)-ethanol (EtOH) binary mixture. Molecular docking analysis delineates considerable noncovalent sandwiched pi-pi stacking interactions of CBIQD with the pyrimidine rings as well as with imidazole rings of dG 6 and dG 2 base pairs of B-DNA double helix, which probably suffices the design strategy adopted. Overall, a strategic design to synthesize a highly fluorescent and potential bioactive agent is executed to revolutionize the fluorophore field due its enormous progressive importance in biochemical applications. PMID- 26816265 TI - C-type natriuretic peptide in combination with sildenafil attenuates proliferation of rhabdomyosarcoma cells. AB - Rhabdomyosarcoma (RMS) is a malignant mesenchymal tumor and the most common soft tissue sarcoma in children. Because of several complications associated with intensive multimodal therapies, including growth disturbance and secondary cancer, novel therapies with less toxicity are urgently needed. C-type natriuretic peptide (CNP), an endogenous peptide secreted by endothelial cells, exerts antiproliferative effects in multiple types of mesenchymal cells. Therefore, we investigated whether CNP attenuates proliferation of RMS cells. We examined RMS patient samples and RMS cell lines. All RMS clinical samples expressed higher levels of guanylyl cyclase B (GC-B), the specific receptor for CNP, than RMS cell lines. GC-B expression in RMS cells decreased with the number of passages in vitro. Therefore, GC-B stable expression lines were established to mimic clinical samples. CNP increased cyclic guanosine monophosphate (cGMP) levels in RMS cells in a dose-dependent manner, demonstrating the biological activity of CNP. However, because cGMP is quickly degraded by phosphodiesterases (PDEs), the selective PDE5 inhibitor sildenafil was added to inhibit its degradation. In vitro, CNP, and sildenafil synergistically inhibited proliferation of RMS cells stably expressing GC-B and decreased Raf-1, Mitogen activated protein kinase kinase (MEK), and extracellular signal-regulated kinase (ERK) phosphorylation. These results suggested that CNP in combination with sildenafil exerts antiproliferative effects on RMS cells by inhibiting the Raf/MEK/ERK pathway. This regimen exerted synergistic effects on tumor growth inhibition without severe adverse effects in vivo such as body weight loss. Thus, CNP in combination with sildenafil represents a promising new therapeutic approach against RMS. PMID- 26816269 TI - Mononuclear Nonheme High-Spin Iron(III)-Acylperoxo Complexes in Olefin Epoxidation and Alkane Hydroxylation Reactions. AB - Mononuclear nonheme high-spin iron(III)-acylperoxo complexes bearing an N methylated cyclam ligand were synthesized, spectroscopically characterized, and investigated in olefin epoxidation and alkane hydroxylation reactions. In the epoxidation of olefins, epoxides were yielded as the major products with high stereo-, chemo-, and enantioselectivities; cis- and trans-stilbenes were oxidized to cis- and trans-stilbene oxides, respectively. In the epoxidation of cyclohexene, cyclohexene oxide was formed as the major product with a kinetic isotope effect (KIE) value of 1.0, indicating that nonheme iron(III)-acylperoxo complexes prefer C?C epoxidation to allylic C-H bond activation. Olefin epoxidation by chiral iron(III)-acylperoxo complexes afforded epoxides with high enantioselectivity, suggesting that iron(III)-acylperoxo species, not high-valent iron-oxo species, are the epoxidizing agent. In alkane hydroxylation reactions, iron(III)-acylperoxo complexes hydroxylated C-H bonds as strong as those in cyclohexane at -40 degrees C, wherein (a) alcohols were yielded as the major products with high regio- and stereoselectivities, (b) activation of C-H bonds by the iron(III)-acylperoxo species was the rate-determining step with a large KIE value and good correlation between reaction rates and bond dissociation energies of alkanes, and (c) the oxygen atom in the alcohol product was from the iron(III) acylperoxo species, not from molecular oxygen. In isotopically labeled water (H2(18)O) experiments, incorporation of (18)O from H2(18)O into oxygenated products was not observed in the epoxidation and hydroxylation reactions. On the basis of mechanistic studies, we conclude that mononuclear nonheme high-spin iron(III)-acylperoxo complexes are strong oxidants capable of oxygenating hydrocarbons prior to their conversion into iron-oxo species via O-O bond cleavage. PMID- 26816270 TI - Identification of a thrombomodulin interaction site on thrombin-activatable fibrinolysis inhibitor that mediates accelerated activation by thrombin. AB - BACKGROUND: Thrombin-activatable fibrinolysis inhibitor (TAFI) is a human plasma zymogen that provides a molecular connection between coagulation and fibrinolysis. TAFI is activated through proteolytic cleavage by thrombin, thrombin in complex with the endothelial cell cofactor thrombomodulin (TM) or plasmin. Evidence from several studies suggests that TM and TAFI make direct contact at sites remote from the activating cleavage site to facilitate acceleration of thrombin-mediated TAFI activation. The elements of TAFI structure that allow accelerated activation of thrombin by TM are incompletely defined. OBJECTIVES: To identify TM interaction regions on TAFI that mediate acceleration of activation by thrombin and therefore indicate TM binding sites on TAFI. METHODS: We mutated selected surface-exposed charged residues on TAFI to alanine in order to identify sites that mediate acceleration of activation by TM. The kinetics of activation of the mutants by thrombin in the presence or absence of TM, as well as their thermal stabilities and antifibrinolytic potentials, were determined. RESULTS: TAFI variants R15A, E28A, K59A, D75A/E77A/D78A, E99A and E106A all exhibited moderately reduced catalytic efficiencies of activation by thrombin-TM. TAFI variants R377A and, particularly, R12A and R12A/R15A exhibited severely reduced activation by thrombin-TM that was not explained by differences in activation by thrombin alone. CONCLUSIONS: We have identified R12 as a critical residue for the activation of TAFI by thrombin-TM, extending a previous report that identified a role for this residue. R12 is likely to directly bind to TM while another key residue, R377, may affect the thrombin-TAFI interaction specifically in the presence of TM. PMID- 26816271 TI - Am I ready to return to work? Assisting cancer survivors to determine work readiness. AB - PURPOSE: A critical initial step in work re-entry involves the determination of work readiness. Cancer survivors have requested increased health care provider involvement in their work readiness decisions. However, there has been no exploration of current practices in determining work readiness, and thus no specific recommendations regarding how to assist survivors in answering the question: Am I ready to return to work? METHODS: To explore return to work following cancer and the workplace supports survivors require, we completed an exploratory qualitative study. We conducted semi-structured interviews with (i) cancer survivors (n = 16) and (ii) health care/vocational service providers (n = 16). Data were analyzed using thematic analysis. Themes specific to work readiness are discussed. RESULTS: Three key processes were deemed relevant to determining work readiness by health care providers and survivors: (1) assessing functional abilities in relation to job demands; (2) identifying survivor strengths and barriers to return to work; and (3) identifying supports available in the workplace. Challenges to work readiness determinations, were described by survivors and providers, related to: (i) the complexity of cancer, (ii) the accuracy of work readiness determinations, and (iii) the lack of established processes for addressing work goals. CONCLUSIONS: Health care providers need to work collaboratively with survivors to determine if they are physically, cognitively, and emotionally ready to return to work, and with workplaces to determine if they are prepared to provide the necessary supports. Further stakeholder collaboration is also warranted. IMPLICATIONS FOR CANCER SURVIVORS: Supports from health care providers in determining work readiness can ensure survivors do not return to work either "too early" or "too late." PMID- 26816273 TI - Assessment of MLC tracking performance during hypofractionated prostate radiotherapy using real-time dose reconstruction. AB - By adapting to the actual patient anatomy during treatment, tracked multi-leaf collimator (MLC) treatment deliveries offer an opportunity for margin reduction and healthy tissue sparing. This is assumed to be especially relevant for hypofractionated protocols in which intrafractional motion does not easily average out. In order to confidently deliver tracked treatments with potentially reduced margins, it is necessary to monitor not only the patient anatomy but also the actually delivered dose during irradiation. In this study, we present a novel real-time online dose reconstruction tool which calculates actually delivered dose based on pre-calculated dose influence data in less than 10 ms at a rate of 25 Hz. Using this tool we investigate the impact of clinical target volume (CTV) to planning target volume (PTV) margins on CTV coverage and organ-at-risk dose. On our research linear accelerator, a set of four different CTV-to-PTV margins were tested for three patient cases subject to four different motion conditions. Based on this data, we can conclude that tracking eliminates dose cold spots which can occur in the CTV during conventional deliveries even for the smallest CTV-to-PTV margin of 1 mm. Changes of organ-at-risk dose do occur frequently during MLC tracking and are not negligible in some cases. Intrafractional dose reconstruction is expected to become an important element in any attempt of re planning the treatment plan during the delivery based on the observed anatomy of the day. PMID- 26816272 TI - An Open Receptor-Binding Cavity of Hemagglutinin-Esterase-Fusion Glycoprotein from Newly-Identified Influenza D Virus: Basis for Its Broad Cell Tropism. AB - Influenza viruses cause seasonal flu each year and pandemics or epidemic sporadically, posing a major threat to public health. Recently, a new influenza D virus (IDV) was isolated from pigs and cattle. Here, we reveal that the IDV utilizes 9-O-acetylated sialic acids as its receptor for virus entry. Then, we determined the crystal structures of hemagglutinin-esterase-fusion glycoprotein (HEF) of IDV both in its free form and in complex with the receptor and enzymatic substrate analogs. The IDV HEF shows an extremely similar structural fold as the human-infecting influenza C virus (ICV) HEF. However, IDV HEF has an open receptor-binding cavity to accommodate diverse extended glycan moieties. This structural difference provides an explanation for the phenomenon that the IDV has a broad cell tropism. As IDV HEF is structurally and functionally similar to ICV HEF, our findings highlight the potential threat of the virus to public health. PMID- 26816274 TI - Focus on Skeletal Bone Diseases - Osteoporosis and Paget's Disease of Bone. PMID- 26816276 TI - Current Aspects of Fragility Fracture Repair. AB - Due to the demographic developments worldwide, fragility fractures represent an increasing problem for the public health system. The risk of developing osteoporosis increases with age and is relatively higher in women and in the Caucasian population. The stability of bone is reduced because of accentuation of the normal loss of bone mass in ageing, leading to an increased susceptibility to fracture with an increased rate of complications after surgical stabilization. Due to this, the orthopedic surgeon has to assess the quality of the bone during preoperative planning and select the implants and postoperative care accordingly to achieve the best. Over the last 10 years fixed locking implants have been introduced into clinical practice. These represent a new type of angle stable fixation devices that address the mechanical instability between bone and implant. The novel problems associated with this device are due to higher cut-out rates when the bone structure is altered and mass is reduced. The developments in joint replacement have also resulted in longer standing times and lower complication rates with immediate fullweight-bearing after implantation. However, to date, little is known about the mechanisms of fracture healing in osteoporosis or fragility fractures. One future approach may be in supporting biological fracture healing by regenerative therapies using growth hormones and/or (stem) cells. The most frequent initial clinical symptom of osteoporosis is a fracture without a relevant trauma. At this stage, the trauma surgeon should initiate diagnostic procedures, treatment of osteoporosis and tertiary prevention according to the European guidelines. Ultimately, all female patients older than 50 years and all male patients older than 60 years with fractures should be assessed and treated for bone quality. Orthogeriatric specialists or interdisciplinary orthogeriatric teams should initiate a specific surgical treatment followed by early rehabilitation in order to allow the elderly patient to return to daily living as soon as possible. PMID- 26816275 TI - Pathophysiology and Pathomorphology of Osteoporosis. AB - Osteoporosis is a disease that leads to fragility fractures due to the loss of bone mass and bone microstructure. This review presents an update on the fundamental pathophysiological and pathomorphological mechanisms of bone loss. Pathomorphological characteristics such as perforations and microcallus formations are explained. The physiological relevance of the remodeling process and its control by local paracrine, systemic endocrine, and central neural signaling pathways are discussed. Hormones, such as estrogen, follicle stimulating hormone, and leptin, transcription factors, such as Runx2 and osterix, and the wnt signaling pathway are discussed in terms of their roles in bone cell differentiation and function. On the basis of current knowledge, osteoporosis can be diagnosed and treated and fractures can be prevented. However, it is likely that new and even more effective diagnostic and therapeutic strategies will emerge as our understanding of the remodeling process that controls osteoblast and osteoclast function increases. PMID- 26816277 TI - Postoperative Protocol in the Prevention of Fragility Fractures in Patients with Osteoporosis-Related Fractures. AB - Osteoporosis is a multifactorial disorder that requires advanced diagnostic evaluation tools. It should not be considered to be an inevitable disease entity or as a logical consequence of the physiological ageing process. Osteoporosis can be diagnosed and - more importantly - properly treated. It is therefore incomprehensible that most of the patients with diagnosed osteoporosis do not receive a specific pharmacotherapeutic treatment. Since orthopedic trauma surgeons most often see a patient with an osteoporosis-associated fracture on a first-hand basis, they, after providing adequate treatment of the fracture, must play a key role in initiating the primary diagnostics and therapy according to national or international guidelines for patients with previous osteoporotic fractures. Treatment should be closely coordinated with general practitioners so that a continuation of the therapy initiated in the hospital can be guaranteed. Basic measures for fracture prevention, including dietary supplements of calcium and vitamin D, should be recommended and implemented for all patients, whereas only those patients with the diagnosis of a manifest osteoporosis should receive a specific pharmacotherapy. Antiresorptive and anabolic drugs that are licensed for the treatment of men or postmenopausal women with osteoporosis have been shown to effectively reduce the incidence of vertebral and non-vertebral fractures. An evaluation of the treatment efficiency should also be performed, such as routine clinical re-evaluation and the measuring of the bone mineral density by dual X-ray absortiometry, every 18-24 months after the initiation of the pharmacotherapy. PMID- 26816278 TI - The Second Most Common Bone Disease: A Review on Paget's Disease of Bone. AB - Paget disease of bone (PDB) is the second most common metabolic bone disease. It is a chronic disease with a mono- or polyostotic appearance that is characterized by an increased bone turnover. The orthopedic surgeon is often confronted with such symptoms and complications as bone pain, skeletal deformities, and pathologic fractures caused by the "out-of-balance bone remodeling process". Careful evaluation of the clinical and radiographic findings is necessary to determine whether treatment of PDB is indicated. The mode of action of effective pharmacological treatments consists of reducing the increase in osteoclast mediated bone resorption that characterizes the disease. Bisphosphonates are the compounds of choice for PDB therapy; these are readily available and have received approval. Patients with PDB are at increased risk for surgical complications, such as blood loss and heterotopic bone formation, if operative treatment is necessary. However, advances in surgical techniques and accompanying medical treatment could potentially improve the overall outcome of these patients. To achieve that goal, careful perioperative interdisciplinary management and monitoring are essential. PMID- 26816279 TI - Management of Morel-Lavallee Lesion Associated with Pelvic and/or Acetabular Fractures. AB - OBJECTIVE: Management of Morel-Lavallee soft tissue lesion (MLL) in patients with associated pelvic and/or acetabular fractures is still under discussion. Especially, the sequence of treatment of MLL soft tissue management and osteosynthesis of pelvic and acetabular injury remains controversial. METHODS: We report all consecutive patients with MLL associated with pelvic ring and/or acetabular fractures during an 8-year period at our hospital. Surgical access and techniques were analyzed concerning complications and outcome. RESULTS: Altogether, 20 patients were included in the study. One patient was treated conservatively and MLL healed without complications; 19 patients had an operative treatment of MLL. In 15 patients debridement was performed within one day after injury and in four patients with delay of 5 days at least. Ten patients had surgery for an associated pelvic ring or acetabular fracture. In four of them MLL was operated before, in six patients simultaneously to osteosynthesis. In three patients, the same surgical approach for osteosynthesis and debridement of MLL was used; none of them showed postoperative complications. Altogether, in nine operated patients (47.4%) MLL healed without any complications. Nine operated patients presented prolonged wound healing, however, during long term follow-up, all patients showed complete healing of the MLL. One patient died during resuscitive surgical procedures. CONCLUSIONS: We recommend debridement for early and delayed treatment of MLL. Osteosynthesis during first debridement may be performed without adverse outcome. Identical surgical access for both procedures can be used. In case of repeated surgical debridement VAC((r)) therapy may be a helpful tool for dead space reduction and wound conditioning. PMID- 26816280 TI - Mortality Distribution in a Trauma System: From Data to Health Policy Recommendations. AB - INTRODUCTION: Trimodal distribution of deaths and the golden hour concepts are in part responsible for the genesis of all modern trauma systems but these concepts have been challenged recently. Our aim was to describe distribution of death in trauma using data from a trauma system and discuss what could be done from the organizational point of view to improve outcome. METHODS: We included all traumatic deaths occurring between 2001 and 2005 in a trauma system. Data on age, gender, time and place of injury, time of first and second hospital arrival, cause of trauma and type of accident, hospital characteristics, dominant injury and time of death were collected for this study. Formortality distribution the variable time was transformed applying a natural logarithm. RESULTS: A total of 1,436 deaths occurred over a period of 53 months; 52% at the scene, 18% in the level I trauma center, 21% in level III trauma center and the remaining in level IV/V trauma center. Death distribution using a logarithmic scale in minutes showed four peaks: deaths at the scene, deaths in the first hours, deaths in the first 2 days and finally, deaths in the second week that we referred as 2 min, 2 h, 2 days and 2 weeks peak. We found statistically significant differences in age and dominant injury concerning timing of death. CONCLUSIONS: A tetramodal pattern of death distribution could be described. Our data support the need to focus on the treatment of severe head injuries namely in the intensive care environment. PMID- 26816281 TI - Helsinki Trauma Outcome Study 2005: Audit on Outcome in Trauma Management in Adult Patients in Southern Part of Finland. AB - The outcome performance of the adult patients trauma care in Helsinki University Hospital was compared with a sample of English hospitals. This was a first time such an audit on trauma care was conducted in Finland. Helsinki University Hospital submitted the Trauma Audit and Research Network (TARN, UK) data of adult trauma patients during 1 year period (from 1 September 2004 to 31 August 2005). Patients younger than 16 years were excluded. The outcome performance was assessed by TARN prediction model using the TARN database as reference. There were total of 1,717 patients in Helsinki and 16,774 patients in English hospitals fulfilling the study inclusion criteria, and 1,635 (95.2% of total) eligible patients in Helsinki and 15,269 (91.0% of total) in England were used for analysis. The patients were older and the mean ISS was higher in Helsinki (mean ISS in Helsinki 14 vs. 11 in England). The standardized W statistic (a measure of survival variation from the expected mean, per 100 patients) was + 3.0 (confidence intervals + 2.3 to + 3.8) for Helsinki University Hospital and + 0.2 (confidence intervals -0.1 to 0.4) for English hospitals. These results suggest that the organization of trauma care in Helsinki University Hospital area is more effective in preventing death after trauma in adults than that covering the present sample of English hospitals. PMID- 26816282 TI - A Survey on Trauma Systems and Education in Europe. AB - PURPOSE: To assess the current stage of trauma system development and trauma surgery training in Europe. METHODS: Email-based survey from 53 physicians representing 25 European countries. RESULTS: On a scale of 0-10, the mean (SD) score for trauma system development was 5.4 (2.4) and for trauma surgery specialization 4.1 (2.9). There was a significant positive correlation between trauma system development and trauma surgery specialization (p = 0.018). Countries with ties to the Austro-German surgical tradition had higher scores both in trauma system development (p = 0.003) and in trauma surgery specialization (p = 0.000), whereas the size, economic performance or geographical location were not associated with either. CONCLUSIONS: Despite the great variation from country to country, three trends in developing trauma care and education can be identified: trauma system development based exclusively on major (life-threatening) trauma care (the old United States model), combining trauma and emergency surgery into a single regionalized system (the acute care surgery model), or maintaining the orthopedic surgery-orientated all-inclusive trauma care model as practiced in most central European countries today. Although each country and region might proceed along their own line depending on local circumstances, some kind of general guidelines and recommendations at least at the European Union level would be urgently needed. PMID- 26816283 TI - Bogota-VAC - A Newly Modified Temporary Abdominal Closure Technique. AB - BACKGROUND: We present Bogota-VAC, a newly modified temporary abdominal closure (TAC) technique for open abdomen condition after abdominal compartment syndrome (ACS). METHODS: A thin isolation bag (Bogota bag) and a vacuum assisted closure (VAC) system were combined. A matching bag was tension-free fixed on the abdominal fascia by fascia suture. A ring shaped black polyurethane foam of the VAC system was placed into the gap between Bogota bag, abdominal fascia and the wound edge. A constant negative topic pressure of 50-75 mmHg was used in the VAC system. RESULTS: Intra-abdominal pressure (IAP: 22 +/- 2 mmHg) of four patients with ACS after severe traumatic brain injury and one patient with isolated ACS after blunt abdominal trauma decreased significantly (p = 0.01) after decompressive laparotomy and treatment with Bogota-VAC (IAP: 10 +/- 2 mmHg) and remained low, measured via urinary bladder pressure. Intracranial pressure (ICP) in the four traumatic brain injury patients decreased from 42 +/- 13 mmHg to 15 +/- 3 mmHg after abdominal decompression. Cerebral perfusion pressure (57 +/- 14 mmHg) increased to 74 +/- 2 mmHg. CONCLUSION: The advantage of the presented Bogota-VAC is leak tightness, wound conditioning (soft tissue/fascia), skin protection and facilitation of nursing in combination with highest volume reserve capacity (VRC), thus preventing recurrent increased intra-abdominal and intracranial pressure in the initial phase after decompression of ACS compared to other TAC techniques. PMID- 26816284 TI - Quantification of Reaming Debris at the Fracture Gap of Diaphyseal A2 and A3 Fractures After Reamed Intramedullary Nailing of the Sheep Tibia. AB - BACKGROUND: The aim of this study was to visualize the intramedullary bone debris after reamed nailing of long bones. To date, there is no protocol to quantify bone debris in the fracture gap. The hypothesis was to show if there are differences between A2 and A3 fractures. METHODS: In this trial 17 sheep tibiae were used. On the medullary isthmus eight A2 und nine A3 fractures were produced. Afterwards, reposition, closure of the soft tissue and reaming procedure up to 10% of the bonecortex were done. For internal fixation, a plastic implant was used. The region of interest was scanned with the Micro-CT 80 and the fracture gap was contoured from a special software (SCANCO Medical AG, Switzerland). The threshold for the reaming debris was set at 549.9 mgHA/cm(3). The analysis of the bone debris located at the fracture gap was measured by percent of debris volume to gap volume. For statistical analysis the Wilcoxon test was used and a level of significance of p < 0.05 was chosen. RESULTS: The fracture gap width ranged from 0.3 to 1.7 mm in both groups. Comparing A2 and A3 fractures there was no significant difference concerning the percentage of reaming debris at the fracture gap. The Median of A2 fractures was 20.5 and 21% for A3 fractures. CONCLUSIONS: The results show reaming produces intramedullary bonegrafting. Despite different fracture planes of A2 and A3 fractures, no significant differences in the amount of reaming debris located at the fracture gap could be found. However the percental rate of reaming debris at the fracture gap of plain fractures is negligible. This research shows that there is potential for reaming debris to be applied effectively as a prophylactic and osteogenetic autograft. Together with the high stability of the intramedullary nail an all embracing concept of osteosynthesis could be established. PMID- 26816285 TI - Should Echogenic Material in the Urinary Bladder Noticed on FAST Preclude Urinary Catheter Insertion in a Trauma Patient Until Further Evaluation? AB - BACKGROUND: Serious urethral and bladder injuries are most often associated with severe blunt trauma. The most common diagnostic tool used to assess lower urinary tract injuries is a retrograde urethrogram. However, the decision to place a Foley catheter is often made on clinical grounds during initial stabilization phase of a trauma victim. If there is a clinical suspicion of a urethral injury, a Foley catheter should not be introduced until further evaluation is made. Focused abdominal sonography for trauma (FAST) is a major tool for primary evaluation of trauma victims. Treating trauma patients, we encountered an unusual "pick up", namely, blood clots in the urinary bladder in two patients. CASE REPORT: We report on two cases of severely traumatized patients on which FAST examination detected an echogenic material in the bladder. This correlated with severe injuries to the urethra and urinary bladder. Moreover, ignorance of this finding in a patient without obvious clinical signs of urethral injury (Patient 1) led to a Foley catheter insertion, and as a consequence, a complex jatrogenic injury to the urethra. On the basis of this study, we hypothesize that the presence of an echogenic material on FAST examination should be considered blood until proven otherwise, and a urinary bladder catheter should not be passed, even in the absence of clinical signs of urethral injury. Since urogenital trauma is rare, this concept should be validated in the prospective study in a high-volume trauma center. PMID- 26816286 TI - Blunt Left Extrahepatic Bile Duct Injury: Case Report and Literature Review. AB - BACKGROUND: Extrahepatic biliary tract injuries following blunt abdominal trauma are very rare and pose a diagnostic and therapeutic challenge. CASE REPORT: We report a case of blunt liver injury with left extrahepatic duct transection following a motor vehicle collision. Technetium 99m dimethyliminodiacetic acid scan confirmed a bile leak and endoscopic retrograde cholangiopancreatography (ERCP) diagnosed the injury of the left extrahepatic duct. Management was initially conservative, consisting of external drainage along with trials of stent placement. Ultimately, partial left hepatectomy was required to definitively treat the injury. CONCLUSION: In the setting of suspected biliary tract injury, early ERCP is essential to localize a leak and guide management decisions. In the event of a confirmed bile leak, a trial of nonoperative management consisting of endoscopic ductal decompression along with percutaneous drainage may initially be warranted although is not always successful. PMID- 26816287 TI - Aseptic Osteonecrosis of the Humeral Head After Anterior Shoulder Dislocation. AB - Anterior shoulder dislocation is a very common trauma and the main complications are well documented. We report a case of aseptic osteonecrosis of the humeral head following an isolated episode of anterior glenohumeral dislocation without fracture that, to our knowledge, has never been reported in the literature.A 17 year-old male patient sustained an anterior glenohumeral dislocation following a sport accident. It was managed by reduction and immobilization. A radiologically identified aseptic osteonecrosis appeared 6 months later. The instability had been arthroscopically treated. At a follow-up of 4 years, the osteonecrosis has been stabilized leaving a mild arthrosis with stiffness, but without pain. PMID- 26816288 TI - Transanal Small Bowel Evisceration: An Unusual Presentation of Rectal Impalement. AB - Traumatic transanal small bowel evisceration is a rare condition usually associated with suction injuries or blunt abdominal trauma. We report the first case of intestinal evisceration through the anus caused by penetrating trauma (rectal impalement). Additionally, we performed a literature review of all English language articles since 1970 concerned with traumatic transanal small bowel evisceration. Mechanisms of injury and the surgical management are discussed. PMID- 26816289 TI - Higher Caffeinated Coffee Intake Is Associated with Reduced Malignant Melanoma Risk: A Meta-Analysis Study. AB - BACKGROUND: Several epidemiological studies have determined the associations between coffee intake level and skin cancer risk; however, the results were not yet conclusive. Herein, we conducted a systematic review and meta-analysis of the cohort and case-control studies for the association between coffee intake level and malignant melanoma (MM) risk. METHODS: Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015). Study-specific risk estimates were pooled under the random-effects model. RESULTS: Two case control studies (846 MM patients and 843 controls) and five cohort studies (including 844,246 participants and 5,737 MM cases) were identified. For caffeinated coffee, the pooled relative risk (RR) of MM was 0.81 [95% confidential interval (95% CI) = 0.68-0.97; P-value for Q-test = 0.003; I2 = 63.5%] for those with highest versus lowest quantity of intake. In the dose response analysis, the RR of MM was 0.955 (95% CI = 0.912-0.999) for per 1 cup/day increment of caffeinated coffee consumption and linearity dose-response association was found (P-value for nonlinearity = 0.326). Strikingly, no significant association was found between the decaffeinated coffee intake level and MM risk (pooled RR = 0.92, 95% CI = 0.81-1.05; P-value for Q-test = 0.967; I2 = 0%; highest versus lowest quantity of intake). CONCLUSIONS: This meta-analysis suggested that caffeinated coffee might have chemo-preventive effects against MM but not decaffeinated coffee. However, larger prospective studies and the intervention studies are warranted to confirm these findings. PMID- 26816290 TI - Changes in the Bioactive Compounds Content of Soybean as a Function of Grain Moisture Content and Temperature during Long-Term Storage. AB - Soybean is a rich source of bioactive compounds, such as phenolic acids, flavonoids, isoflavones, carotenoids, and tocopherols. The amount of bioactive compounds in freshly harvested soybeans and their derived products has been determined; however, when they are used in the food industry, soybeans are generally stored prior to being processed. This study aimed to evaluate the effects of soybean moisture content (12%, 15%, and 18%) and storage temperature (11, 18, 25, and 32 degrees C) on the free phenolic, total flavonoid, vanillic acid, total carotenoid, and delta- and gamma-tocopherol content of soybeans stored for 12 mo. Moreover, the ABTS and DPPH radical scavenging activities of phenolic extracts were determined. There was an increase in free phenolics and total flavonoids in the stored grains compared with the grains on the 1st d of storage. Vanillic acid showed a decrease in soybeans stored at 15% and 18% moisture content and 25 or 32 degrees C, which indicated some degradation into other metabolites. Total carotenoid content decreased as a function of storage temperature and showed some temperature-dependent degradation. The delta- and gamma-tocopherol content also tended to decrease in grains stored at 15% or 18% moisture content or 25 or 32 degrees C, regardless of the moisture content studied. PMID- 26816291 TI - Transplant Antennae and Host Brain Interact to Shape Odor Perceptual Space in Male Moths. AB - Behavioral responses to odors rely first upon their accurate detection by peripheral sensory organs followed by subsequent processing within the brain's olfactory system and higher centers. These processes allow the animal to form a unified impression of the odor environment and recognize combinations of odorants as single entities. To investigate how interactions between peripheral and central olfactory pathways shape odor perception, we transplanted antennal imaginal discs between larval males of two species of moth Heliothis virescens and Heliothis subflexa that utilize distinct pheromone blends. During metamorphic development olfactory receptor neurons originating from transplanted discs formed connections with host brain neurons within olfactory glomeruli of the adult antennal lobe. The normal antennal receptor repertoire exhibited by males of each species reflects the differences in the pheromone blends that these species employ. Behavioral assays of adult transplant males revealed high response levels to two odor blends that were dissimilar from those that attract normal males of either species. Neurophysiological analyses of peripheral receptor neurons and central olfactory neurons revealed that these behavioral responses were a result of: 1. the specificity of H. virescens donor olfactory receptor neurons for odorants unique to the donor pheromone blend and, 2. central odor recognition by the H. subflexa host brain, which typically requires peripheral receptor input across 3 distinct odor channels in order to elicit behavioral responses. PMID- 26816292 TI - A Randomized Controlled Trial to Test the Effectiveness of an Immersive 3D Video Game for Anxiety Prevention among Adolescents. AB - Adolescent anxiety is debilitating, the most frequently diagnosed adolescent mental health problem, and leads to substantial long-term problems. A randomized controlled trial (n = 138) was conducted to test the effectiveness of a biofeedback video game (Dojo) for adolescents with elevated levels of anxiety. Adolescents (11-15 years old) were randomly assigned to play Dojo or a control game (Rayman 2: The Great Escape). Initial screening for anxiety was done on 1,347 adolescents in five high schools; only adolescents who scored above the "at risk" cut-off on the Spence Children Anxiety Survey were eligible. Adolescents' anxiety levels were assessed at pre-test, post-test, and at three month follow-up to examine the extent to which playing Dojo decreased adolescents' anxiety. The present study revealed equal improvements in anxiety symptoms in both conditions at follow-up and no differences between Dojo and the closely matched control game condition. Latent growth curve models did reveal a steeper decrease of personalized anxiety symptoms (not of total anxiety symptoms) in the Dojo condition compared to the control condition. Moderation analyses did not show any differences in outcomes between boys and girls nor did age differentiate outcomes. The present results are of importance for prevention science, as this was the first full-scale randomized controlled trial testing indicated prevention effects of a video game aimed at reducing anxiety. Future research should carefully consider the choice of control condition and outcome measurements, address the potentially high impact of participants' expectations, and take critical design issues into consideration, such as individual- versus group-based intervention and contamination issues. PMID- 26816293 TI - Preliminary Experience with a New Multidirectional Videoendoscope for Neuroendoscopic Surgical Procedures. AB - PURPOSE: We assessed the applicability of a new multidirectional videoendoscope (digiCAMeleon, Karl Storz GmbH, Tuttlingen, Germany) in various neuroendoscopic procedures. METHODS: A 4-mm-diameter rigid videoendoscope (digiCAMeleon, Karl Storz GmbH, Tuttlingen, Germany) with 1 sensor and an internal LED light source was tested. The device offers a resolution of 1920 x 1080 pixels and weighs ~ 215 g. The prototype was tested on three cadaveric heads using three different approaches: a) endoscopic endonasal transsphenoidal; b) frontal transcortical intraventricular; c) supraorbital. RESULTS: We identified several major benefits of the integrated system as applied to endoscopic endonasal, transcortical intraventricular, and endoscopic supraorbital keyhole approaches. These included improved maneuverability of the scope on account of reduced bulk and integration of the camera and fiberoptic light components, a variable angle of view from 0-70 degrees, and a novel feature that can be activated to maintain orientation of the surgical horizon. Our preliminary report highlights the potential for handling the videoendoscope in one hand, as one would a microsurgical instrument. The videoendoscope harbors all its electronic and lighting data into a unique and thin cable, thus resembling a modern "all-in-one" computer technology. Because of its reduced weight and ergonomic shape, controlling its movements is very easy and comfortable, even in the microsurgical environment. Furthermore, the videoendoscope offers the unique feature of orienting the horizon of vision, thanks to the possibility of offering angled views while working; this helps the surgeons to stay oriented with direct visualization and improved control of the instruments over a specific area of interest. CONCLUSIONS: The videoendoscope prototype represents an HD-image quality versatile tool in a neurosurgical environment, thanks to its reduced weight and dimensions; in these preliminary simulations, we have identified optimized visibility and maneuverability as major benefits of this novel surgical adjunct. PMID- 26816294 TI - Spearhead Nanometric Field-Effect Transistor Sensors for Single-Cell Analysis. AB - Nanometric field-effect-transistor (FET) sensors are made on the tip of spear shaped dual carbon nanoelectrodes derived from carbon deposition inside double barrel nanopipettes. The easy fabrication route allows deposition of semiconductors or conducting polymers to comprise the transistor channel. A channel from electrodeposited poly pyrrole (PPy) exhibits high sensitivity toward pH changes. This property is exploited by immobilizing hexokinase on PPy nano FETs to give rise to a selective ATP biosensor. Extracellular pH and ATP gradients are key biochemical constituents in the microenvironment of living cells; we monitor their real-time changes in relation to cancer cells and cardiomyocytes. The highly localized detection is possible because of the high aspect ratio and the spear-like design of the nano-FET probes. The accurately positioned nano-FET sensors can detect concentration gradients in three dimensional space, identify biochemical properties of a single living cell, and after cell membrane penetration perform intracellular measurements. PMID- 26816295 TI - A classification system of intraocular lens dislocation sites under operating microscopy, and the surgical techniques and outcomes of exchange surgery. AB - PURPOSE: The aim of this study was to examine the recent status of intraocular lens (IOL) dislocation according to a classification system based on vertical dislocation position, as well as the surgical techniques and outcomes of IOL exchange surgery. METHODS: The medical records of 230 eyes from 214 consecutive patients who experienced IOL dislocation and underwent exchange surgery between 2006 and 2014 were reviewed. Vertical dislocation sites observed preoperatively under operating microscopy were examined, along with the surgical techniques and outcomes of IOL exchange. RESULTS: Dislocation sites included (1) the anterior chamber (12.2 %), (2) pseudophakodonesis (19.1 %), (3) the anterior vitreous cavity (47.4 %), (4) trap door-like dislocation (dangling in the peripheral vitreous cavity; 16.1 %), and (5) the retinal surface (5.2 %). The IOL retained in the anterior segment was moved onto the iris by pulling it up through the limbal side ports with an anterior vitrectomy (67.8 %), or by pushing it up from the pars plana with an anterior vitrectomy (26.5 %), while the IOL dropped on the retina was lifting it up from the retina after pars plana vitrectomy (5.7 %). Mean uncorrected and distance-corrected visual acuity significantly improved postoperatively (p < 0.0001). Major complications included a marked elevation in intraocular pressure (7.8 %), pupillary capture (6.5 %), and vitreous hemorrhage (2.6 %). CONCLUSIONS: Based on the classification system, approximately 95 % of dislocated IOLs were retained in the anterior segment, and these IOLs were exchanged using an anterior approach through limbal incisions with an anterior vitrectomy. Visual acuity improved significantly, and serious complications were uncommon, probably because the IOL exchange techniques were standardized and simplified without pars plana vitrectomy. PMID- 26816296 TI - Ocular Findings of Myotonic Dystrophy Type 1 in the Korean Population. AB - PURPOSE: To investigate ocular findings in a Korean population with myotonic dystrophy type 1 (DM1). METHODS: A total of 24 Korean patients with DM1, ranging in age from 4 to 71 years, were examined over a period from June 2004 to May 2014. Ophthalmologic examinations including visual acuity assessment, slit-lamp biomicroscopy, ocular motility, cycloplegic refraction, and fundus examination were performed in all patients, and brain magnetic resonance (MR) imaging was performed in 15 patients. RESULTS: The ocular findings, in order of decreasing prevalence, were as follows: cataract (17 patients, 71 %), myopia (22 eyes, 59 %), hyperopia (13 eyes, 35 %), ptosis (6 patients, 25 %), epiretinal membrane (5 patients, 21 %), exotropia (4 patients, 17 %), ocular motility limitations (4 patients, 17 %), blepharitis (2 patients, 8 %), pigmentary retinopathy (2 patients, 8 %), lid lag (1 patient, 4 %), esotropia (1 patient, 4 %), and myelinated nerve fiber layer (1 patient, 4 %). Five of eight patients (63 %) with CTG repeats >= 700 underwent cataract extraction, as did one of 13 patients (8 %) with CTG repeats < 700 (P = 0.014). All four patients who showed limited ocular motility had CTG repeats >= 1000. Brain MR imaging showed periventricular white matter lesions in three patients, diffuse brain atrophy in two patients, and extraocular muscle atrophy in two patients. CONCLUSIONS: Korean patients with DM1 showed a high incidence of exotropia in comparison to Caucasian patients with DM1. Our study suggests a possible correlation between the severity of cataract and ocular motility limitation and the size of CTG repeats. PMID- 26816297 TI - Discharge planning from hospital. AB - BACKGROUND: Discharge planning is a routine feature of health systems in many countries. The aim of discharge planning is to reduce hospital length of stay and unplanned readmission to hospital, and to improve the co-ordination of services following discharge from hospital.This is the third update of the original review. OBJECTIVES: To assess the effectiveness of planning the discharge of individual patients moving from hospital. SEARCH METHODS: We updated the review using the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 9), MEDLINE, EMBASE, CINAHL, the Social Science Citation Index (last searched in October 2015), and the US National Institutes of Health trial register (ClinicalTrials.gov). SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared an individualised discharge plan with routine discharge care that was not tailored to individual participants. Participants were hospital inpatients. DATA COLLECTION AND ANALYSIS: Two authors independently undertook data analysis and quality assessment using a pre-designed data extraction sheet. We grouped studies according to patient groups (elderly medical patients, patients recovering from surgery, and those with a mix of conditions) and by outcome. We performed our statistical analysis according to the intention-to treat principle, calculating risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous data using fixed-effect meta-analysis. When combining outcome data was not possible because of differences in the reporting of outcomes, we summarised the reported data in the text. MAIN RESULTS: We included 30 trials (11,964 participants), including six identified in this update. Twenty-one trials recruited older participants with a medical condition, five recruited participants with a mix of medical and surgical conditions, one recruited participants from a psychiatric hospital, one from both a psychiatric hospital and from a general hospital, and two trials recruited participants admitted to hospital following a fall. Hospital length of stay and readmissions to hospital were reduced for participants admitted to hospital with a medical diagnosis and who were allocated to discharge planning (length of stay MD - 0.73, 95% CI - 1.33 to - 0.12, 12 trials, moderate certainty evidence; readmission rates RR 0.87, 95% CI 0.79 to 0.97, 15 trials, moderate certainty evidence). It is uncertain whether discharge planning reduces readmission rates for patients admitted to hospital following a fall (RR 1.36, 95% CI 0.46 to 4.01, 2 trials, very low certainty evidence). For elderly patients with a medical condition, there was little or no difference between groups for mortality (RR 0.99, 95% CI 0.79 to 1.24, moderate certainty). There was also little evidence regarding mortality for participants recovering from surgery or who had a mix of medical and surgical conditions. Discharge planning may lead to increased satisfaction for patients and healthcare professionals (low certainty evidence, six trials). It is uncertain whether there is any difference in the cost of care when discharge planning is implemented with patients who have a medical condition (very low certainty evidence, five trials). AUTHORS' CONCLUSIONS: A discharge plan tailored to the individual patient probably brings about a small reduction in hospital length of stay and reduces the risk of readmission to hospital at three months follow-up for older people with a medical condition. Discharge planning may lead to increased satisfaction with healthcare for patients and professionals. There is little evidence that discharge planning reduces costs to the health service. PMID- 26816298 TI - Inhaled non-steroid anti-inflammatories for children and adults with bronchiectasis. AB - BACKGROUND: Chronic neutrophilic inflammation, in both the presence and absence of infection, is a feature of bronchiectasis in adults and children. The anti inflammatory properties of non-steroid anti-inflammatory drugs (NSAIDs) may be beneficial in reducing airway inflammation, thus potentially improving lung function and quality of life in patients with bronchiectasis. OBJECTIVES: To evaluate the efficacy of inhaled NSAIDs in the management of non-cystic fibrosis bronchiectasis in children and adults:* during stable bronchiectasis; and* for reduction of:? severity and frequency of acute respiratory exacerbations; and? long-term pulmonary decline. SEARCH METHODS: We searched the Cochrane Airways Group Trials Register, which includes reports identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We also searched the trial registry ClinicalTrials.gov and the World Health Organization (WHO) trial portal. We carried out the latest searches on 22 September 2015. SELECTION CRITERIA: All randomised controlled trials comparing inhaled NSAIDs versus a control (placebo or usual treatment) in children or adults with bronchiectasis not related to cystic fibrosis. DATA COLLECTION AND ANALYSIS: We reviewed the results of searches against predetermined criteria for inclusion. MAIN RESULTS: One small, short-term trial was eligible for inclusion. We included this study of 25 adults with chronic lung disease (only 32% of people included in the trial had bronchiectasis), as the other conditions were linked to development of bronchiectasis, and all were characterised by chronic sputum production. We were not able to obtain separate data for people with a diagnosis of bronchiectasis. We judged that the study was at a high risk of selection bias.The primary outcome (mean difference in control of bronchiectasis severity, quality of life (Qol), cough scores) was not reported in the included study. The single trial in adults reported a significant reduction in sputum production over 14 days for the treatment group (inhaled indomethacin) compared with the placebo group (mean difference (MD) -75.00 g/day; 95% confidence interval (CI) -134.61 to -15.39) and a significant improvement in the Borg Dyspnoea Scale score (MD -1.90, 95% CI -3.15 to -0.65). We noted no significant differences between groups in lung function or blood indices and no reported adverse events. AUTHORS' CONCLUSIONS: No new studies of adults or children have been conducted since the last version of this review was published. Therefore, final conclusions have not changed. Current evidence is insufficient to support or refute the use of inhaled NSAIDs for the management of bronchiectasis in adults or children. One small trial reported a reduction in sputum production and improved dyspnoea among adults with chronic lung disease who were treated with inhaled indomethacin, indicating that additional studies on the efficacy of NSAIDs for treatment of patients with bronchiectasis are warranted. PMID- 26816299 TI - Water precautions for prevention of infection in children with ventilation tubes (grommets). AB - BACKGROUND: Following middle ear ventilation tube (tympanostomy tube or grommet) insertion, most surgeons advise that a child's ears should be kept dry during the immediate postoperative period. Following the initial period some surgeons will permit swimming or bathing, whereas other surgeons will recommend ongoing water precautions. A large number of studies have been conducted to explore the association between water exposure and ear infections in children with ventilation tubes, however a range of differing conclusions exist regarding the need for water precautions and there is wide variation in clinical practice. OBJECTIVES: To assess the effectiveness of water precautions for the prevention of ear infections in children with ventilation tubes (grommets), at any time while the tubes are in place. SEARCH METHODS: The Cochrane ENT Trials Search Co ordinator searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 8); PubMed; EMBASE; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 1 September 2015. SELECTION CRITERIA: Randomised controlled trials recruiting children (0 to 17 years) with ventilation tubes and assessing the effect of water precautions while the tubes are in place. We considered all forms of water precautions, including behavioural (i.e. avoidance or swimming/bathing restrictions) and mechanical (ear plugs/moulds or hats/bands). DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcome measures were episodes of otorrhoea and adverse effects; secondary outcomes were antimicrobial prescriptions for ear infections, ventilation tube extrusion, surgical intervention to remove ventilation tubes and hearing outcomes. MAIN RESULTS: Two randomised controlled trials recruiting a total of 413 patients met the criteria for inclusion in our review; one study had a low risk of bias and the other study had a high risk of bias. Ear plugs versus control One study recruited 201 children (aged six months to six years) who underwent myringotomy and ventilation tube insertion. The study compared an intervention group who were instructed to swim and bathe with ear plugs with a control group; the participants were followed up at one-month intervals for one year. This study, with low risk of bias, showed that the use of ear plugs results in a small but statistically significant reduction in the rate of otorrhoea from 1.2 episodes to 0.84 episodes in the year of follow-up (mean difference (MD) -0.36 episodes per year, 95% confidence interval (CI) -0.45 to -0.27). There was no significant difference in ventilation tube extrusion or hearing outcomes between the two study arms. No child required surgical intervention to remove ventilation tubes and no adverse events were reported. Water avoidance versus control Another study recruited 212 children (aged three months to 12 years) who underwent myringotomy and ventilation tube insertion. The study compared an intervention group who were instructed not to swim or submerge their heads while bathing with a control group; the participants were followed up at three-month intervals for one year. This study, with high risk of bias, did not show any evidence of a reduction or increase in the rate of otorrhoea (1.17 episodes per year in both groups; MD 0 episodes, 95% CI -0.14 to 0.14). No other outcomes were reported for this study and no adverse events were reported. Quality of evidence The overall quality (GRADE) of the body of evidence for the effect of ear plugs on the rate of otorrhoea and the effect of water avoidance on the rate of otorrhoea are low and very low respectively. AUTHORS' CONCLUSIONS: The baseline rate of ventilation tube otorrhoea and the morbidity associated with it is usually low and therefore careful prior consideration must be given to the efficacy, costs and burdens of any intervention aimed at reducing this rate.While there is some evidence to suggest that wearing ear plugs reduces the rate of otorrhoea in children with ventilation tubes, clinicians and parents should understand that the absolute reduction in the number of episodes of otorrhoea appears to be very small and is unlikely to be clinically significant. Based on the data available, an average child would have to wear ear plugs for 2.8 years to prevent one episode of otorrhoea.Some evidence suggests that advising children to avoid swimming or head immersion during bathing does not affect rates of otorrhoea, although good quality data are lacking in this area. Currently, consensus guidelines therefore recommend against the routine use of water precautions on the basis that the limited clinical benefit is outweighed by the associated cost, inconvenience and anxiety.Future high-quality studies could be undertaken but may not be thought necessary. It is uncertain whether further trials in this area would change the findings of this review or have an impact on practice. Any future high-quality research should focus on determining whether particular groups of children benefit more from water precautions than others, as well as on developing clinical guidelines and their implementation. PMID- 26816300 TI - Breastfeeding or nipple stimulation for reducing postpartum haemorrhage in the third stage of labour. AB - BACKGROUND: Oxytocin and prostaglandin are hormones responsible for uterine contraction during the third stage of labour. Receptors in the uterine muscles are stimulated by exogenous or endogenous oxytocin leading to uterine contractions. Nipple stimulation or breastfeeding are stimuli that can lead to the secretion of oxytocin and consequent uterine contractions. Consequently, uterine contractions can reduce bleeding during the third stage of labour. OBJECTIVES: To investigate the effects of breastfeeding or nipple stimulation on postpartum haemorrhage (PPH) during the third stage of labour. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 July 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing breast stimulation, breastfeeding or suckling for PPH in the third stage of labour were selected for this review. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion in terms of risk of bias and independently extracted data. Disagreements were resolved by a third review author. MAIN RESULTS: We included four trials (4608 women), but only two studies contributed data to the review's analyses (n = 4472). The studies contributing data were assessed as of high risk of bias overall. One of these studies was cluster randomised and conducted in a low-income country and the other study was carried out in a high-income country. All four included studies assessed blood loss in the third stage of labour. Birth attendants estimated blood loss in two trials. The third trial assessed the hematocrit level on the second day postpartum to determine the effect of the bleeding. The fourth study measured PPH >= 500 mL. Nipple stimulation versus no treatmentOne study (4385 women) compared the effect of suckling versus no treatment. Blood loss was not measured in 114 women (59 in control group and 55 in suckling group). After excluding twin pregnancies, stillbirths and neonatal deaths, the main analyses for this trial were performed on 4227 vaginal deliveries. In terms of maternal death or severe morbidity, one maternal death occurred in the suckling group due to retained placenta (risk ratio (RR) 3.03, 95% confidence interval (CI) 0.12 to 74.26; one study, participants = 4227; very low quality evidence); severe morbidity was not mentioned. Severe PPH (>= 1000 mL) was not reported in this study.The incidence of PPH (>= 500 mL) was similar in the suckling and no treatment groups (RR 0.95, 95% CI 0.77 to 1.16; one study, participants = 4227; moderate quality). There were no group differences between nipple stimulation and no treatment regarding blood loss in the third stage of labour (mean difference (MD) 2.00, 95% CI -7.39 to 11.39; one study, participants = 4227; low quality). The rates of retained placenta were similar (RR 1.01, 95% CI 0.14 to 7.16; one study, participants = 4227; very low quality evidence), as were perinatal deaths (RR 1.06, 95% CI 0.57 to 1.98; one study, participants = 4271; low quality), and maternal readmission to hospital (RR 1.01, 95% CI 0.14 to 7.16; one study, participants = 4227; very low quality). We downgraded the evidence for this comparison for risk of bias concerns in the one included trial (inappropriate analyses for cluster design) and for imprecision (wide CIs crossing the line of no difference and, for some outcomes, few events).Many maternal secondary outcomes (including side effects) were not reported. Similarly, most neonatal secondary outcomes were not reported. Nipple stimulation versus oxytocinAnother study compared the effect of nipple stimulation (via a breast pump) with oxytocin. Eighty-seven women were recruited but only 85 women were analysed. Severe PPH >= 1000 mL and maternal death or severe morbidity were not reported.There was no clear effect of nipple stimulation on blood loss (MD 15.00, 95% CI -24.50 to 54.50; one study, participants = 85; low quality evidence), or on postnatal anaemia compared to the oxytocin group (MD -0.40, 95% CI -2.22 to 1.42; one study, participants = 85; low quality evidence). We downgraded evidence for this comparison due to risk of bias concerns in the one included trial (alternate allocation) and for imprecision (wide CIs crossing the line of no difference and small sample size).Many maternal secondary outcomes (including side effects) were not reported, and none of this review's neonatal secondary outcomes were reported. AUTHORS' CONCLUSIONS: None of the included studies reported one of this review's primary outcomes: severe PPH >= 1000 mL. Only one study reported on maternal death or severe morbidity. There were limited secondary outcome data for maternal outcomes and very few secondary outcome data for neonatal outcomes.There was no clear differences between nipple stimulation (suckling) versus no treatment in relation to maternal death, the incidence of PPH (>= 500 mL), blood loss in the third stage of labour, retained placenta, perinatal deaths or maternal readmission to hospital. Whilst these data are based on a single study with a reasonable sample size, the quality of these data are mostly low or very low.There is insufficient evidence to evaluate the effect of nipple stimulation for reducing postpartum haemorrhage during the third stage of labour and more evidence from high-quality studies is needed. Further high-quality studies should recruit adequate sample sizes, assess the impact of nipple stimulation compared to uterotonic agents such as syntometrine and oxytocin, and report on important outcomes such as those listed in this review. PMID- 26816301 TI - Colchicine for prevention of cardiovascular events. AB - BACKGROUND: Colchicine is an anti-inflammatory drug that is used for a wide range of inflammatory diseases. Cardiovascular disease also has an inflammatory component but the effects of colchicine on cardiovascular outcomes remain unclear. Previous safety analyses were restricted to specific patient populations. OBJECTIVES: To evaluate potential cardiovascular benefits and harms of a continuous long-term treatment with colchicine in any population, and specifically in people with high cardiovascular risk. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ClinicalTrials.gov, WHO International Clinical Trials Registry, citations of key papers, and study references in January 2015. We also contacted investigators to gain unpublished data. SELECTION CRITERIA: Randomised controlled trials (parallel group or cluster design or first phases of cross-over studies) comparing colchicine over at least six months versus any control in any adult population. DATA COLLECTION AND ANALYSIS: Primary outcomes were all-cause mortality, myocardial infarction, and adverse events. Secondary outcomes were cardiovascular mortality, stroke, heart failure, non-scheduled hospitalisations, and non scheduled cardiovascular interventions. We conducted predefined subgroup analyses, in particular for participants with high cardiovascular risk. . MAIN RESULTS: We included 39 randomised parallel-group trials with 4992 participants. Colchicine had no effect on all-cause mortality (RR 0.94, 95% CI 0.82 to 1.09; participants = 4174; studies = 30; I2 = 27%; moderate quality of evidence). There is uncertainty surrounding the effect of colchicine in reducing cardiovascular mortality (RR 0.34, 95% CI 0.09 to 1.21, I2 = 9%; participants = 1132; studies = 7; moderate quality of evidence). Colchicine reduced the risk for total myocardial infarction (RR 0.20, 95% CI 0.07 to 0.57; participants = 652; studies = 2; moderate quality of evidence). There was no effect on total adverse events (RR 1.52, 95% CI 0.93 to 2.46; participants = 1313; studies = 11; I2 = 45%; very low quality of evidence) but gastrointestinal intolerance was increased (RR 1.83, 95% CI 1.03 to 3.26; participants = 1258; studies = 11; I2 = 74%; low quality of evidence). Colchicine showed no effect on heart failure (RR 0.62, 95% CI 0.10 to 3.88; participants = 462; studies = 3; I2 = 45%; low quality of evidence) and no effect on stroke (RR 0.38, 95% CI 0.09 to 1.70; participants = 874; studies = 3; I2 = 45%; low quality of evidence). Reporting of serious adverse events was inconsistent; no event occurred over 824 patient-years (4 trials). Effects on other outcomes were very uncertain. Summary effects of RCTs specifically focusing on participants with high cardiovascular risk were similar (4 trials; 1230 participants). AUTHORS' CONCLUSIONS: There is much uncertainty surrounding the benefits and harms of colchicine treatment. Colchicine may have substantial benefits in reducing myocardial infarction in selected high-risk populations but uncertainty about the size of the effect on survival and other cardiovascular outcomes is high, especially in the general population from which most of the studies in our review were drawn. Colchicine is associated with gastrointestinal side effects based on low-quality evidence. More evidence from large-scale randomised trials is needed. PMID- 26816302 TI - Brief Report: Spatial Heterogeneity of Systemic Sclerosis in France: High Prevalence in the Northeast Region. AB - OBJECTIVE: Alsace is a region in eastern France with a population of ~2 million. All residents have high access to health care and an accredited referral center for SSc. Seeking care outside of this region is difficult because of the peculiar geography. The aim of this study was to assess the prevalence and spatial variation of systemic sclerosis (SSc) in eastern France. METHODS: Data for SSc patients were obtained from 3 sources (all general practitioners and community specialists, capillaroscopy centers, and all public and private hospital records) and were used to estimate the prevalence of SSc. Surviving patients who resided in Alsace on January 1, 2008 and fulfilled the American College of Rheumatology and/or the LeRoy and Medsger criteria were included in this study. The clinical characteristics of the patients were also assessed. Potentially incomplete case ascertainment was corrected by capture-recapture analyses. Geographic disparities were assessed by spatial cluster analysis and by comparing our results with those for other geographic areas in the world for which data derived using similar methodology were available. RESULTS: The review of 499 potential cases identified a total of 244 SSc patients. A trend toward a west-to-east gradient was observed but did not reach statistical significance. According to log-linear modeling, an estimated 83.87 additional cases were missed. Thus, the SSc prevalence was 228.42 cases per million adult inhabitants of Alsace (95% confidence interval 203.70 253.14); this prevalence was significantly higher than that in 2 other regions of France and comparable with the reported prevalence in Detroit, Michigan. CONCLUSION: The stringent methodology used in the current study is very likely to provide an accurate estimation of the prevalence of SSc. Design similarity with 3 other surveys extends the scope of the results by identifying geographic disparities that were previously indistinguishable due to methodologic differences. PMID- 26816303 TI - Focus on malleolar fractures. PMID- 26816304 TI - Principles of operative treatment of malleolar fractures today. AB - Ankle fractures continue to be a common injury. They involve various mechanisms of injury and produce, when treated correctly, fairly good results. Although non displaced stable malleolar fractures are treated safely by conservative means, displaced unstable fractures are still the domain of open reduction and internal fixation (ORIF), as recommended by the AO Group. The principles of the operative treatment of these fractures are discussed in this paper, illuminating the surgical technique and biomechanics of lateral, medial and posterior malleolar fractures. Even though there have been no fundamental changes in the treatment of these fractures in the last several years, new implants such as angular-stable plates and new surgical techniques such as the minimally invasive plate osteosynthesis (MIPO) technique help to treat these fractures more individually, depending on the type of fracture, quality of bone and soft tissue conditions. PMID- 26816305 TI - The Volkmann dogma: a retrospective, long-term, single-center study. AB - INTRODUCTION: There has been (and still is) some controversy about the treatment of malleolar fractures with an additional fracture of the posterior malleolus (Volkmann triangle) in the last few years. Should a posterior malleolus with a fragment that is larger than 25% of the articular surface be fixed? Can long-term results be influenced by the fixation of the Volkmann triangle? MATERIALS AND METHODS: In a consecutive series of 43/56 patients with a dislocated malleolar fracture, clinical and radiological results were analyzed after a follow-up of 7.3 years (4-11 years). There were 15 men with an average age of 53 years and 28 women with an average age of 62 years, respectively. Eleven fragments were fixed. At inspection, 16 patients displayed a cartilage lesion at the talar dome. RESULTS: No or only slight arthrosis was found on X-rays of 37/43 patients. Six patients showed moderate or severe arthrosis. The Olerud-Molander score was 95.5 in patients without a Volkmann triangle, 98.5 in the presence of a small, unfixed fragment, and 90.6 with a large fixed fragment. Patients with no cartilage damage on perioperative inspection presented less severe arthrosis in the long-term results, while those with documented cartilage damage during the operation had more severe arthrosis. The Olerud-Molander score was 97.2 without cartilage damage and 94.5 with cartilage damage. CONCLUSION: In conclusion, the presence of a Volkmann triangle impairs prognosis; fixation, even with anatomic results, does not return the score to "normal." Cartilage damage seems to play a crucial role in the long-term outcome. PMID- 26816306 TI - Treatment of malunion in ankle fractures. AB - Malunions are fractured bones that have healed in pathological positions. This leads to nonphysiological load transfer. Clinical symptoms at the ankle may include swelling, pain and impaired function. Lateral, posterolateral or posteromedial subluxation of the talus will be visible on the radiographs. Surgical correction may be indicated if the malunion is symptomatic. Different osteotomies have been described, but the goal of surgery will always be the reduction and retention of the subluxed talus in an effort to recreate stable conditions. Eighty percent of patients show good results with significant pain reduction in mid-term follow-up studies. Ankle arthrodesis after corrective osteotomy is rarely necessary. PMID- 26816307 TI - Treatment of ankle osteoarthritis: arthrodesis versus total ankle replacement. AB - While ankle arthrodesis has remained the gold standard treatment for symptomatic primary, secondary, and posttraumatic ankle arthritis, more recently, total ankle replacement (TAR) has seen considerable improvement in terms of biomechanics, function, and complication rates. However, while in the long-term degeneration of the adjacent joints is almost always found on radiographs after ankle arthrodesis, the longevity of TAR is still insufficient and does not match that of total knee and hip joints. The current review article focuses on the treatment of ankle arthritis by means of arthrodesis and TAR. PMID- 26816309 TI - A novel fuzzy-logic inference system for predicting trauma-related mortality: emphasis on the impact of response to resuscitation. AB - INTRODUCTION: Trauma scoring aims for quantification and uniform reporting of trauma-related outcomes. Despite significant advances in trauma scoring, the exact time period at which relevant calculations should be made is not clear. Considering the importance of response to resuscitation, calculation of trauma scores after a period of resuscitation can allow better discrimination of patients who will survive. METHODS: A fuzzy-logic inference system, which is completely based on expert opinion and uses Glasgow Coma Scale (GCS) and systolic blood pressure at arrival to emergency room (ER) and their response to resuscitation as inputs, was developed. Records of the last 150 trauma patients admitted to our surgical intensive care unit (ICU) were used for calculations related to Injury Severity Score (ISS), Revised Trauma Score (RTS), Trauma and Injury Severity Score, and A Severity Characterization of Trauma (ASCOT) systems. Calculation of trauma severity and predicted mortality was performed at different time intervals during resuscitation [at arrival to emergency room (ER), after 1 h of resuscitation, and at ICU admission]. The performance of conventional systems and fuzzy-logic system was compared. RESULTS: Mean ISS was 32.31 +/- 14.01. All systems included showed acceptable discriminative power. Among the conventional systems calculated at emergency room admission, ISS was the best performing [receiver operating characteristics (ROC), 0.9033] and RTS was the worst (ROC, 0.8106). Their performances were improved by up to 13% by use of post resuscitation physiologic variables. Fuzzy-logic inference system performed slightly better (ROC, 0.9247) then the conventional systems calculated at arrival to ER. CONCLUSIONS: Response to resuscitation has significant impact on trauma mortality and must be considered in trauma scoring and mortality prediction. Fuzzy logic provides important opportunities for design of better predictive systems. PMID- 26816308 TI - Definitive treatment in a spiral-fracture of the distal humerus shaft with severe osteoporosis after two failed osteosynthesis: problem and solution. A case report and literature review. AB - INTRODUCTION: Osteoporotic fractures in the elderly are often complicated by delayed union, pseudarthrosis or implant failure and are associated with considerable morbidity and prolonged reconvalescence. At present there is cumulating recommendation to treat this kind of fractures with angular stable implants. CASE PRESENTATION: Herein, we report on the successful definitive treatment of a displaced comminuted spiral-fracture of the distal humerus shaft in an 89-year-old woman after two attempts of internal fixation with angular stable implants had failed in severely osteoporotic bone. CONCLUSION: The present case illustrates the problems we have faced with after a single locking plate fixation, especially in poor bone, and shows a possible solution by performing a double(-locking)-plate fixation. PMID- 26816310 TI - Neutrophil-derived circulating free DNA (cf-DNA/NETs), a potential prognostic marker for mortality in patients with severe burn injury. AB - The predictive value of circulating free DNA/neutrophil extracellular traps (cf DNA/NETs) has recently been shown in patients with major trauma for sepsis, multiple organ failure, and mortality. Here we report on the predictive potential of cf-DNA/NETs for mortality in patients with severe burn injury. In a prospective study 32 patients with severe burn injury were included. Blood samples were sequentially obtained on day 1, 3, 5, and 7 after admission. cf DNA/NETs was directly quantified from plasma by means of rapid fluorescence assay. Time kinetics of cf-DNA/NETs were correlated with clinical data, C reactive protein (CRP), procalcitonin (PCT), and interleukin (IL)-6. Furthermore sensitivity, specificity, and positive and negative predictive value, as well as receiver operation characteristic (ROC) curves were calculated. Seven patients died within the first month after burn injury. cf-DNA/NETs values from these patients were significantly increased already on day 1 and 3 after admission compared with patients who survived (p < 0.01). In contrast, PCT levels of nonsurvivors were significantly elevated on day 3 and 5 (p < 0.01), while CRP and IL-6 did not show any significant difference between survivors and nonsurvivors. At a cutoff of 255 ng/ml, cf-DNA/NETs had sensitivity of 0.8 and specificity of 0.74. ROC revealed largest areas under the curve (AUC) for cf-DNA/NETs on day 1 (0.851) and 3 (0.883) after admission. For all values between day 1 and 7, AUC was 0.815. cf-DNA/NETs seems to be a rapid, valuable marker for prediction of mortality in burn patients. A larger confirmation trial ought to be carried out. PMID- 26816312 TI - Traumatic adrenal gland injury: epidemiology and outcomes in a major Australian trauma center. AB - INTRODUCTION: Adrenal gland injury (ADGI) is quite rare and mostly associated with other organ injuries secondary to blunt thoracoabdominal trauma. Bilateral ADGI has severe consequences if not discovered in the treatment course of trauma victims. PURPOSE: To review our experience of management of ADGI, epidemiology, and outcomes in a major Australian trauma institute. METHODS: A retrospective analysis of all patients presenting with thoracoabdominal trauma to the Alfred Hospital who had been diagnosed with adrenal gland injury between July 2001 and July 2007. RESULTS: Of 3,921 patients with blunt thoracoabdominal injuries, 2.4% were identified with blunt ADGI (70 males and 26 women, age range 15-85 years). Right adrenal injuries occurred in 72.9%, left adrenal injuries in 22.9%, and bilateral ADGI in 4.2%. Computed tomography (CT) scan findings revealed 82.2% of acute injuries to be hyperdense hematoma expanding and distorting the adrenal gland. Periadrenal stranding and hemorrhagic changes around the adrenal limbs were seen in 12.5%. Oval or round lesions were seen in 3.1%. Surgery was performed in 25% of the study group for associated thoracoabdominal injuries. Patients with left adrenal gland injury had higher rates of mortality and morbidity, and length of stay. CONCLUSION: ADGI is being increasingly recognized with the widespread use of CT scan in the evaluation of multitrauma patients. ADGI is usually self-limiting and typically managed nonoperatively. Acute adrenal insufficiency should be considered and investigated in case of unexplained hypotension in uni- or bilateral ADGI. PMID- 26816311 TI - Predictors of missed injuries in hospitalized trauma patients in the emergency department. AB - AIM: To determine the extent of missed injuries in patients hospitalized with major trauma in a Turkish Level 1 emergency department. We also tried to identify the primary factors contributing to each missed injury and to determine their subsequent adverse short-term clinical outcomes. METHODS: This is a retrospective analysis of prospectively collected data on a cohort of trauma patients. Trauma patients were divided into two groups: patients with missed injury and others. Logistic regression was used to define factors affecting "missed injury". RESULTS: A total of 670 hospitalized trauma patients were included. The incidence of missed injuries in the patients and the rate of missed injury per patient were 13.3% (95% CI 6-20) and 1.64, respectively. The most frequently missed diagnosis was injuries of the musculoskeletal system (38%; 95% CI 30-46). It was "clavicle fracture and/or dislocation" (35%; 95% CI 16-53) when the rate of missed diagnosis according to the frequency of the specific injury was calculated. A multiple logistic regression analysis showed that the predictors of missed injuries were patient's age (OR 0.74, 95% CI 0.63-0.87), total number of injuries (OR 1.74, 95% CI 1.38-2.20), and ISS (OR 1.10, 95% CI 1.03-1.18). Radiological errors were prominent in almost 90% (95% CI 85-95). Missed injury caused additional hospital stay (30%; 95% CI 21-40) and additional surgery was required (15%; 95% CI 8-23). CONCLUSION: The study highlights the need for a trauma team approach and the need for support of radiological report in the ED. PMID- 26816313 TI - Management of isolated duodenal rupture due to blunt abdominal trauma: case series and literature review. AB - INTRODUCTION: Duodenal injuries are uncommon and are associated with significant morbidity and mortality due to delayed diagnosis (in the case of blunt trauma) or associated major vascular injuries (in the case of penetrating trauma). Isolated blunt injuries may have a subtle clinical presentation, and are particularly difficult to diagnose when the perforation is located in the retroperitoneal part of the duodenum. MATERIALS AND METHODS: This paper presents in company with three cases of successfully treated isolated duodenal injuries due to blunt trauma, focusing on with their preoperative diagnosis, surgical management and final out comes. CONCLUSIONS: Early diagnosis and successful surgical planning require experience and clinical suspicion on the part of the surgeon, as well as meticulous laparotomy results. PMID- 26816314 TI - Appendicular tuberculosis: review of 155 published cases and a report of two cases. AB - PURPOSE: This paper provides an overview of the literature on appendicular tuberculosis (ATB) between 1909 and 2010. METHODS: We present two cases of primary ATB and a literature review of studies on ATB published in English and accessed via the Pubmed and Google Scholar databases. RESULTS: One hundred fifty five published cases of ATB were reviewed, and two patients with primary ATB, treated and followed in our clinic, were reported. The age range of the patients (62 females, 60 males and 33 with unnoted gender) was between 2 and 60 years, with a mean age of 27.1 +/- 10.6 years. Of the patients who had applied to hospital, 59 had acute right lower quadrant pain, 46 had recurrent right lower quadrant pain, 19 had generalized pain, and 10 had chronic abdominal symptoms suggestive of subacute intestinal obstruction, while 47 patients were operated on with a diagnosis of acute appendicitis, 24 with recurrent appendicitis, 19 with TB peritonitis, 14 with mass in the right lower quadrant, 13 with subacute intestinal obstruction, and 7 with ATB. While appendectomy was not performed on 4 patients, one or more of the following procedures were done in the other 151 cases: appendectomy, hemicolectomy, ileocecal resection, or cecectomy. Different anti-tubercular treatment regimens with durations varying from 3 weeks to 18 months were applied to 60 patients. During the follow-up period of 3 weeks to 15 years, mortality occurred in 14 patients, sinus in five, and fistula in one patient. Secondary ATB was detected in 86 patients, primary ATB in 50, and no differential diagnosis could be made in 19 cases. CONCLUSIONS: Tuberculosis is a systemic disease with localized manifestations; therefore, anti-TB therapy must be initiated in any patient whose pathologic specimen reveals tuberculosis. PMID- 26816315 TI - Stabilisation of the elbow in cases of severe disruption of the lateral collateral complex. AB - INTRODUCTION: Rupture of the lateral collateral ligamentous complex of the elbow is a serious injury. If direct repair of the ligamentous complex is not possible, then an alternative method must be found to stabilise the elbow. MATERIALS AND METHODS: We describe a novel method of maintaining stability while allowing early movement in a severe injury to the elbow. CONCLUSION: This technique is a viable alternative to hinged external fixation in patients with severe lateral instability of the elbow joint. PMID- 26816316 TI - Proximal humerus fracture with a pink, pulseless arm in a teenage boy and literature review. AB - Proximal humeral fractures associated with vascular compromise are extremely rare in children. We describe the presentation, diagnosis and management of one such injury in a child. PMID- 26816317 TI - Corynebacterium septic arthritis of the knee presenting as a ruptured septic popliteal cyst. AB - A rare case of a septic knee arthritis presenting as an infected ruptured popliteal cyst is described. Infection of a popliteal cyst is an uncommon complication of septic arthritis and presentation can mimic that of an acute deep vein thrombosis, leading to delay in diagnosis and treatment. Of interest, the typical hallmarks of infection and haematological markers of inflammation were all unremarkable in the current case. This case was of additional interest in that there have been no reports in the literature of Corynebacterium spp. being isolated from an infected popliteal cyst. Invasive infections caused by Corynebacterium spp. seem to have a predilection for patients who are immunocompromised. It is especially important in this subset of patients that delays in diagnosis are avoided by including it in the differential of an immunocompromised patient presenting with unilateral lower-extremity pain and swelling. PMID- 26816318 TI - Transverse dislocation of the elbow with ipsilateral shaft of radius fracture in an adult. AB - STUDY DESIGN: A report of a rare case of transverse dislocation of the elbow associated with fracture of the shaft of the ipsilateral radius. OBJECTIVE: To describe a rare variety of elbow dislocation associated with radial shaft fracture. INTRODUCTION: Transverse dislocation of the elbow is a rare injury and most of the cases have been described in pediatric patients. Association of this injury with fracture of forearm bones is rare. We describe a case of transverse dislocation of the elbow associated with a fracture of the ipsilateral shaft of the radius in an adult. MATERIAL AND METHODS: A 21-year-old male patient sustained trauma to his left upper limb in a traffic accident. Radiographic evaluation revealed transverse dislocation of the elbow and fracture of the shaft of the ipsilateral radius. Closed reduction of the elbow dislocation was carried out followed by open reduction and internal fixation of the fracture. RESULTS: Eight months after trauma, the patient is asymptomatic with complete range of motion and no instability. Radiographs show a well-healed fracture and congruent elbow joint. CONCLUSION: To the best of our knowledge, this is first case of transverse dislocation of the elbow with an ipsilateral radial shaft fracture in an adult. Closed reduction of such dislocations is usually achievable, though open reduction may be required in some case. PMID- 26816319 TI - Limb salvage or amputation? The use of a gentamicin coated nail in a severe, grade IIIc tibia fracture. AB - INTRODUCTION: Severe grade IIIc tibial fractures have limited treatment options. The decision between limb salvage or amputation depends on many factors, including the age and health status of the patient, as well as the soft tissue status and associated injuries. Until recently, intramedullary nailing was not a favoured treatment option in such tibial fractures, since it is associated with an increased risk of deep wound infections and osteomyelitis. MATERIAL AND METHODS: Here we present a case where a novel polylactic acid/gentamicin coated unreamed tibial nail (UTN-PROtect((r))) has been used to successfully salvage the limb of a 17-year-old man, where prolonged external fixation or amputation would have been the standard treatment. RESULTS: This case demonstrates that treating severe grade IIIc tibial fractures with the acid/gentamicin coated unreamed tibial nail (UTN-PROtect((r))) is a viable alternative to prolonged external fixation or amputation. CONCLUSION: The gentamicin-loaded coating of the UTN PROtect((r)) nail, which releases the antimicrobial agent directly at the bone implant inter-face, overcomes the limitation of insufficient antibiotic delivery. Awareness of this case and the existing literature supporting the use of an antibiotic coated nail may assist surgeons in their decisions on how to treat severe grade IIIc fractures. PMID- 26816320 TI - Blue to near-IR energy transfer cascade within a dye-doped polymer matrix, mediated by a photochromic molecular switch. AB - The spectroscopic properties of a poly(methyl methacrylate) matrix doped with a coumarin dye, a cyanine dye, and a photochromic spiropyran dye have been investigated. Before UV irradiation of the matrix, excitation of the coumarin dye results in minimal energy transfer to the cyanine dye. The energy transfer is substantially enhanced following UV irradiation of the matrix, which converts the colourless spiropyran isomer to the coloured merocyanine isomer, which then acts as an intermediate bridge by accepting energy from the coumarin dye and then donating energy to the cyanine dye. This demonstration of a switchable energy transfer cascade should help initiate new research directions in molecular photonics. PMID- 26816321 TI - An Ecological Paradox: The African Wild Dog (Lycaon Pictus) Is Not Attracted to Water Points When Water Is Scarce in Hwange National Park, Zimbabwe. AB - In dry biomes, spatio-temporal variation in surface water resource stocks is pervasive, with unknown effects on the ranging behaviour of large predators. This study assessed the effect of spatial variation in surface water resources on the ranging behaviour of the African wild dog (Lycaon pictus). We analyzed data for 1992 (dry year with 20 water points) and 2000 (wet year with 30 water points) against presence-only data for five packs of L. pictus in a part of Hwange National Park and adjacent smallholder communal farming areas in western Zimbabwe. Modelling the potential habitat for L. pictus using Maxent with distance from water points (Dw) and Normalized Difference Vegetation Index (NDVI) as predictor variables was successful for 2000 (AUC = 0.793) but not successful for 1992 (AUC = 0.423), with L. pictus probability of occurrence near water points being more for year 2000 than for year 1992. The predicted L. pictus range was wider in 1992 (~13888.1 km2) than in 2000 (~958.4 km2) (Test of Proportions, chi2 = 124.52, df = 1, P = 0.00). Using the 2nd order Multitype Nearest Neighbour Distance Function (Gcross), we also observed significant attraction between L. pictus and water points within only ~1km radius for 1992 but up to ~8km radius for 2000. Our study reinforced the notion that surface water resources attract wild dogs in the savannahs but paradoxically less so when water resources are scarce. In particular, our study furthers current understanding of the effects of changing water availability regimes on the endangered L. pictus, providing evidence that the endangered predator's home range encroaches into potential ecological traps (i.e., smallholder communal farming areas) when water resources are scarce. PMID- 26816322 TI - A Latent Class Extension of Signal Detection Theory, with Applications. AB - A latent class extension of signal detection theory is presented and applications are illustrated. The approach is useful for situations where observers attempt to detect latent categorical events or where the goal of the analysis is to select or classify cases. Signal detection theory is shown to offer a simple summary of the observers' performance in terms of detection and response criteria. Implications of the view via signal detection for the training of raters are noted, as are approaches to validating the parameters and classifications. An extension of the signal detection model to more than two latent classes, with a simple restriction on the detection parameters, is introduced. Sample programs to fit the models using software for latent class analysis or software for second generation structural equation modeling are provided. PMID- 26816323 TI - Bayesian Estimation and Model Selection of Multivariate Linear Model with Polytomous Variables. AB - This article provides a Bayesian analysis of the multivariate linear model with polytomous variables. The computational burden due to the intractable multiple integrals induced by the polytomous variables and the model is solved by augmenting the underlying latent continuous measurements of the observed polytomous data. A Gibbs sampler algorithm is implemented to produce the Bayesian estimate. A Bayes factor approach is proposed for model selection, and it is approximated by the Bayesian information criterion (BIC) via the bridge sampling. The proposed methodology is illustrated by examples using multivariate linear regression and multivariate two-way analysis of variance with real data. PMID- 26816324 TI - Multisample Analysis of Multivariate Ordinal Categorical Variables. AB - We study a multiple group model with ordinal categorical observed variables that are manifestations of underlying normal variables. When the objective of an analysis is to compare the locations and dispersions of the underlying continuous variables in different groups, traditional approaches use exact linear constraints on thresholds across groups to identify the model. Though the resultant model facilitates interpretation in multiple group analysis, in some cases the exact linear relationships on thresholds are not appropriate for describing the reality. However, these constraints must be imposed to identify the model. In view of this, we propose to apply across group stochastic constraints on thresholds to identify the model. Stochastic constraints are more practical and flexible than exact constraints, and subsume exact constraints as a special case, and therefore enable the structure of the data to be described in a more realistic way. Using stochastic constraints, we can achieve an identified model that allows the comparison of underlying continuous variables in different groups relatively, and at the same time accommodate the possible differences in thresholds. A Bayesian approach is employed to analyze the model, and prior knowledge can be incorporated into the analysis. It is demonstrated that the parameter estimates can be produced conveniently using the Mx software program, and an illustrative sample Mx input script is presented. A real data set is analyzed with the proposed approach, and results are compared to those obtained by using other prevailing approaches. PMID- 26816325 TI - A Version of Quadratic Regression with Interpretable Parameters. AB - The quadratic regression model is popular and effective in describing a wide variety of data, but it is based on a function whose parameters are not easy to interpret. We suggest an alternative form of the quadratic model that has the same expectation function, but also has the useful feature that its parameters are interpretable. Examples are provided of a simple regression problem and also of a nonlinear mixed-effects model. The models can be estimated with available software. PMID- 26816326 TI - Theoretical and Empirical Comparisons between Two Models for Continuous Item Response. AB - This article analyzes the relations between two continuous response models intended for typical response items: the linear congeneric model and Samejima's continuous response model (CRM). Using a factor analytical (FA) approach based on the assumption of underlying response variables, I describe how a particular case of the CRM can be considered as a nonlinear counterpart of Spearman's FA model. The mathematical relations between the: item-trait regressions, item parameter values, and conditional and marginal distributions of both models are obtained. The results allow (a) the item parameter values of the linear model to be obtained from CRM item parameter values, and (b) the conditions in which the congeneric model will be a good approximation to the CRM to be predicted. The relations described are illustrated using an empirical example and assessed by means of a simulation study. PMID- 26816327 TI - Elaborating the Differential in Differential Psychology. AB - The methods of differential psychology have contributed importantly to the current state of behavioral science, but their limitations continue to be well - publicized in the "experimental versus correlational" literature. The argument developed here is that the value of these methods has been constrained as much by the phenomena to which they are applied as by underlying flaws that render them inferior to classical experimental methods. Some applications of differential methods to alternative phenomena are examined that promise to broaden significantly the contribution that differential methods can make to our understanding of behavior and behavior change. PMID- 26816328 TI - Special cancer microenvironment in human colonic cancer: Concept of cancer microenvironment formed by peritoneal invasion (CMPI) and implication of subperitoneal fibroblast in cancer progression. AB - Clinical outcomes of colorectal cancer are influenced not by tumor size, but by spread into the bowel wall. Although assessment of serosal involvement is an important pathological feature for classification of colon cancer, its diagnostic consistency has been questioned. Using elastic staining, we assessed elastic laminal invasion (ELI) for more objective stratification of deep tumor invasion around the peritoneal surface. In addition, pathological characteristic features of marked tumor budding, fibrosis, and macrophage infiltration in the tumor area with ELI was elucidated. This characteristic tumor area was termed cancer microenvironment formed by peritoneal elastic laminal invasion (CMPI). We elucidated histoanatomical layer-dependent heterogeneity of fibroblast in colonic tissue. Furthermore, subperitoneal fibroblasts (SPFs) play a crucial role in tumor progression and metastasis in CMPI. Our ELI and CMPI concept contributes not only to objective pathological diagnosis, but also sheds light on biological research of special cancer microenvironments detectable in human colorectal cancers. Herein, we describe the diagnostic utility of ELI and morphological alteration in advanced colorectal cancers to determine the phenomenon that occurs when tumors invade around the peritoneal surface. Next, biological research of CMPI is reviewed to stress the importance of pathological research to establish new biological concepts. PMID- 26816329 TI - Diagnosis of adverse local tissue reactions following metal-on-metal hip arthroplasty. AB - Metal-on-metal (MOM) bearing surfaces in hip arthroplasty have distinct advantages that led to the increase in popularity in North America in the early 2000s. However, with their increased use, concerns such as local cytotoxicity and hypersensitivity reactions leading to soft tissue damage and cystic mass formation (known collectively as adverse local tissue reactions (ALTR)) became apparent. The clinical presentation of ALTR is highly variable. The diagnosis of ALTR in MOM articulations in hip arthroplasty can be challenging and a combination of clinical presentation, physical examination, implant track record, component positioning, serum metal ion levels, cross-sectional imaging, histopathologic analysis, and consideration of alternative diagnoses are essential. PMID- 26816330 TI - Revision for taper corrosion at the head-neck junction: pearls and pitfalls. AB - Modular hip replacement components offer numerous advantages, and the modular femoral component has become standard for contemporary total hip implants. Recent reports of mechanically assisted crevice corrosion (MACC) at the head-neck junction, and associated adverse local tissue reactions (ALTRs), have renewed concerns for complications attributed to modularity. This manuscript describes the diagnosis, prognosis, and treatment options for MACC and highlights how appropriate pre-revision evaluation and planning, in conjunction with meticulous surgical technique, should be followed to avoid complications and achieve optimal surgical outcomes. Future directions for research include biomechanical, clinical, and retrieval studies. PMID- 26816331 TI - Correction: Genomic variations of the mevalonate pathway in porokeratosis. PMID- 26816333 TI - Novel Water-Soluble Amphotericin B-PEG Conjugates with Low Toxicity and Potent in Vivo Efficacy. AB - Systemic fungal infections are an increasingly prevalent health problem, especially among immunocompromised patients. Antifungal drug development lags far behind in comparison to other types of antimicrobial drugs. Current commercially available antifungals are limited by their insufficient potency, side effects, drug-drug interactions, developing drug-resistance, and narrow formulation options. Here, we report the preparation and evaluation of two novel PEG amide conjugates of amphotericin B (AMB (1)): AB1 (4) and AM2 (5). These compounds are nonlabile, they are prepared in only two and three synthetic steps, respectively, and they show antifungal activity against a wide range of clinical fungal isolates. Their toxicity is significantly lower, and their water solubility is up to 5000-fold higher than that of AMB (1). In vivo efficacy studies in a mouse model of systemic candidiasis showed that AM2 (5) successfully cured all the mice at concentrations above 3.5 mg/kg body weight. In conclusion, these properties make AB1 (4) and AM2 (5) promising candidates for clinical use. PMID- 26816332 TI - Association of Alterations in Gray Matter Volume With Reduced Evoked-Pain Connectivity Following Short-Term Administration of Pregabalin in Patients With Fibromyalgia. AB - OBJECTIVE: Pregabalin (PGB) is an alpha2 delta calcium-channel subunit ligand that has previously been shown to reduce chronic pain in multiple conditions. Preclinical studies indicate that PGB may down-regulate brain glutamate release while also inhibiting astrocyte induction of glutamatergic synapse formation, and recent clinical findings support the notion that PGB modulates glutamatergic activity and functional brain connectivity in order to produce analgesia. The present study was undertaken to examine concurrent changes in brain gray matter volume (GMV) or evoked-pain connectivity in humans receiving PGB. METHODS: Sixteen female fibromyalgia patients participated in a randomized double-blind 2 period crossover study of PGB versus placebo. Before and after each period, patients underwent high-resolution structural and evoked pressure-pain functional brain imaging. GMV was analyzed using voxel-based morphometry, and functional connectivity during evoked pressure-pain was assessed. RESULTS: PGB administration significantly reduced GMV within the posterior insula bilaterally, whereas there were no significant changes in insular GMV following placebo treatment. GMV reductions in the medial frontal gyrus were also observed when comparing PGB versus placebo treatment, and were associated with reduced clinical pain. These reductions in insular GMV were associated with concomitant reductions in connectivity to the default mode network, which was also associated with reduced clinical pain. CONCLUSION: Short-term PGB treatment altered brain structure and evoked-pain connectivity, and these decreases were associated with reduced clinical pain. We speculate that these fairly rapid changes in GMV may be related to brain neuroplasticity. It is unknown whether these effects are generalizable to other chronic pain states. PMID- 26816334 TI - Conjugation of A and B Blood Group Structures to Silica Microparticles for the Detection of Antigen-Specific B Cells. AB - Silica microparticles were functionalized with A and B blood group carbohydrate antigens (A type I, A type II, B type I, and B type II) to enable the detection and monitoring of ABO antigen-specific B cells. Microparticles were prepared via the Stober synthesis, labeled with an Alexafluor fluorescent dye, and characterized via TEM and fluorescence microscopy. The silica microparticles were functionalized with (3-aminopropyl)trimethoxysilane (APTMS), followed by the use of an established fluorenylmethyloxycarbonyl (Fmoc)-protected PEG-based linker. The terminal Fmoc moiety of the PEG-based linker was then deprotected, yielding free amino groups, to which the A and B antigens were coupled. The carbohydrate antigens were synthesized with a p-nitrophenol ester to enable conjugation to the functionalized silica microparticles via an amide bond. The number of free amine groups available for coupling for a given mass of PEG-functionalized silica microparticles was quantified via reaction with Fmoc-glycine. The antigen functionalized microparticles were then evaluated for their specificity in binding to A and B antigen-reactive B-cells via flow cytometry, and for blocking of naturally occurring antibodies in human serum. Selective binding of the functionalized microparticles to blood group-reactive B cells was observed by flow cytometry and fluorescence microscopy. The modular approach outlined here is applicable to the preparation of silica microparticles containing any carbohydrate antigen and alternative fluorophores or labels. This approach therefore comprises a novel, general platform for screening B cell populations for binding to carbohydrate antigens, including, in this case, the human A and B blood group antigens. PMID- 26816335 TI - Delphinidin, a major anthocyanin, inhibits 3T3-L1 pre-adipocyte differentiation through activation of Wnt/beta-catenin signaling. AB - Delphinidin (Del) is a major anthocyanin that is widely found in pigmented fruits and vegetables. Herein, we investigated the antiadipogenic effect and the molecular mechanism by which Del affects 3T3-L1 preadipocyte differentiation. We found that Del effectively reduced intracellular lipid accumulation and promoted lipolysis while regulating the expression of adipogenic transcription factors and their target genes. This lipid lowering effect of Del was largely limited to the early phase of adipogenesis, which is governed by the delayed cell cycle progression due to G1 cell cycle arrest. Subsequently, Del suppressed the expression of early adipogenic transcription factors, such as C/EBPbeta and C/EBPdelta, as well as that of intermediate markers, C/EBPalpha, PPARgamma, and the PPARgamma-target adipocyte markers adiponectin and aP2 (FABP4). Furthermore, Del treatment activated Wnt1, Wnt10b, the Wnt receptor Fzd2, and the coreceptors Lrp5/6, while it inactivated Gsk3beta, a member of the beta-catenin destruction complex. Moreover, Del treatment stabilized cytoplasmic beta-catenin levels and promoted its nuclear translocation, with subsequent activation of the expression of its downstream target genes, c-Myc and cyclin D1. Our findings therefore suggest that Del can effectively inhibit adipogenesis followed by the stabilization of beta-catenin during early 3T3-L1 differentiation via inhibition of its destructive complexes and activation of Wnt signaling, and may thus be a promising candidate for the prevention of metabolic diseases, including obesity. PMID- 26816336 TI - The effects of chronic cadmium exposure on repeat swimming performance and anaerobic metabolism in brown trout (Salmo trutta) and lake whitefish (Coregonus clupeaformis). AB - This study investigates the effect of chronic Cd exposure on the ability to perform repeat swim challenges in brown trout (Salmo trutta) and lake whitefish (Coregonus clupeaformis). Fish were exposed to waterborne Cd (18nM) in moderately hard water (120mgL(-1) CaCO3) for 30 days. This level of exposure has been shown to cause sublethal physiological disruption and acclimation responses but no impairment of sustained swimming capacity (Ucrit) in single swim challenges. Swim trials were done over the course of the exposure and each one consisted of an initial swim to 85% of the Ucrit of control fish, a 30min recovery period and finally a second swim challenge to determine Ucrit. Plasma and tissue samples were collected before and after each of the swim periods. As expected from previous studies, Cd exposure resulted in significant accumulation of Cd in gills, liver and kidney but not in white muscle. Exposure also induced a loss of plasma Ca followed by subsequent recovery (in lake whitefish but not brown trout) with few mortalities (100% survival for lake whitefish and 93% for brown trout). Both control and exposed fish swam to 85% of the single swim Ucrit and no differences in performance were seen. The Ucrit of unexposed controls in the second swim challenges were not different from the single swim Ucrit. However, second swim performance was significantly reduced in Cd exposed fish, particularly after a week of exposure where 31% and 38% reductions were observed for brown trout and lake whitefish respectively. Swimming to 85% Ucrit resulted in metabolic expenditure with little recovery after 30min. Few differences were observed between control and Cd exposed fish with the exception of a reduction in resting white muscle ATP stores of Cd exposed fish after 1 week of exposure. The results show that chronic sublethal Cd exposure results in an impairment of swimming ability in repeat swim challenges but this impairment is generally not related to metabolic processes in white muscle. PMID- 26816337 TI - Stratification of brachytherapy-treated intermediate-risk prostate cancer patients into favorable and unfavorable cohorts. AB - PURPOSE: To evaluate biochemical failure (BF) and prostate cancer specific mortality (PCSM) in intermediate-risk (IR) brachytherapy patients stratified into favorable and unfavorable cohorts, and to compare those outcomes to patients with low (LR) and high-risk (HR) disease. MATERIAL AND METHODS: From March 1995 till February 2012, 2,502 consecutive patients underwent permanent interstitial brachytherapy for clinically localized prostate cancer. Patients were stratified into risk groups as per the NCCN guidelines with further stratification of the intermediate risk cohort into unfavorable (primary Gleason pattern 4, >= 50% positive biopsies or >= 2 IR features) and favorable cohorts. Median follow-up was 8.5 years. The brachytherapy prescription dose was prescribed to the prostate gland with generous periprostatic margins. Biochemical failure was defined as a PSA > 0.40 ng/ml after nadir. Patients with metastatic prostate cancer or non metastatic castrate resistant disease who died of any cause were classified as dead of prostate cancer. Multiple parameters were evaluated for effect on outcomes. RESULTS: Fifteen year BF for LR, favorable IR, unfavorable IR, and HR were 1.4%, 2.2%, 7.1%, and 11.1% (p < 0.001), respectively. At 15 years, PCSM for LR, favorable IR, unfavorable IR, and HR was 0.3%, 0.6%, 2.2% and 4.6% (p < 0.001), respectively. In multivariate analysis, BF was best predicted by risk group, pre-implant PSA, percent positive biopsies, prostate volume, and ADT duration, while PCSM was most closely related to risk group, percent positive biopsies and prostate volume. CONCLUSIONS: Patients with favorable IR disease have biochemical and PCSM outcomes comparable to those of patients with LR disease. Although unfavorable IR has greater than a 3-fold increased risk of BF and PCSM when compared to favorable IR, the outcomes remain superior to those men with HR disease. PMID- 26816338 TI - Monte Carlo simulations of a novel Micromegas 2D array for proton dosimetry. AB - Modern proton therapy affords control of the delivery of radiotherapeutic dose on fine length and temporal scales. The authors have developed a novel detector technology based on Micromesh Gaseous Structure (Micromegas) that is uniquely tailored for applications using therapeutic proton beams. An implementation of a prototype Micromegas detector for Monte Carlo using Geant4 is presented here. Comparison of simulation results with measurements demonstrates agreement in relative dose along the proton longitudinal dose profile to be 1%. The effect of a radioactive calibration source embedded in the chamber gas is demonstrated by measurements and reproduced by simulations, also at the 1% level. Our Monte Carlo simulations are shown to reproduce the time structure of ionization pulses produced by a double-scattering delivery system. PMID- 26816339 TI - Association between thyroid dysfunction and venous thromboembolism in the elderly: a prospective cohort study. AB - BACKGROUND: Venous thromboembolism (VTE) and subclinical thyroid dysfunction (SCTD) are both common in elderly patients. SCTD has been related to a hypercoagulable state and an increased thromboembolic risk. However, prospective data on the relationship between SCTD and VTE are lacking. OBJECTIVES: To investigate the relationship between SCTD and recurrent VTE (rVTE), all-cause mortality, and thrombophilic biomarkers. Patients Elderly patients with VTE were studied. METHODS: In a prospective multicenter cohort, thyroid hormones and thrombophilic biomarkers were measured 1 year after acute VTE, as both may be influenced by acute thrombosis. We defined subclinical hypothyroidism (SHypo) as elevated thyroid-stimulating hormone (TSH) levels (4.50-19.99 mIU L(-1) ), and subclinical hyperthyroidism (SHyper) as TSH levels of < 0.45 mIU L(-1) , both with normal free thyroxine levels. Outcomes were incidence of rVTE and overall mortality during follow-up starting after the 1-year blood sampling. RESULTS: Of 561 participants (58% with anticoagulation), 6% had SHypo and 5% had SHyper. After 20.8 months of mean follow-up, 9% developed rVTE and 10% died. The rVTE incidence rate was 7.2 (95% confidence interval [CI] 2.7-19.2) per 100 patient years in SHypo participants, 0.0 (95% CI 0.0-7.6) in SHyper participants, and 5.9 (95% CI 4.4-7.8) in euthyroid participants. In multivariate analyses, the sub hazard ratio for rVTE was 0.00 (95% CI 0.00-0.58) in SHyper participants and 1.50 (95% CI 0.52-4.34) in SHypo participants as compared with euthyroid participants, without increased levels of thrombophilic biomarkers. SHyper (hazard ratio [HR] 0.80, 95% CI 0.23-2.81) and SHypo (HR 0.99, 95% CI 0.30-3.29) were not associated with mortality. CONCLUSION: In elderly patients, SHyper may be associated with lower rVTE risks. SHypo showed a non-statistically significant pattern of an association with rVTE, without increased mortality or differences in thrombophilic biomarkers. PMID- 26816340 TI - Macroglossia in advanced amyotrophic lateral sclerosis. AB - INTRODUCTION: An enlarged tongue (macroglossia) has been reported in advanced stage patients with amyotrophic lateral sclerosis (ALS). METHODS: In this study we examined the prevalence of macroglossia and analyzed clinical correlations in 65 ALS patients on tracheostomy-invasive ventilation (TIV). RESULTS: Macroglossia was found in 22 patients (33.8%). Compared with those without macroglossia, patients with macroglossia had a younger age of onset, longer duration of disease and TIV use, lower ALS Functional Rating Scale score, higher body mass index, lower energy intake, more severe communication impairment, and lower oral function. Logistic multivariate analysis showed that body mass index (BMI; P = 0.007) and communication impairment (P = 0.029) were significantly correlated with macroglossia. The duration of TIV use was at the cut-off level of significance (P = 0.05). CONCLUSIONS: Macroglossia may be the result of overfeeding and replacement by fat during long-term TIV use in patients with advanced ALS. Muscle Nerve, 2016 Muscle Nerve 54: 386-390, 2016. PMID- 26816341 TI - Chlorine Gas Sensing Performance of On-Chip Grown ZnO, WO3, and SnO2 Nanowire Sensors. AB - Monitoring toxic chlorine (Cl2) at the parts-per-billion (ppb) level is crucial for safe usage of this gas. Herein, ZnO, WO3, and SnO2 nanowire sensors were fabricated using an on-chip growth technique with chemical vapor deposition. The Cl2 gas-sensing characteristics of the fabricated sensors were systematically investigated. Results demonstrated that SnO2 nanowires exhibited higher sensitivity to Cl2 gas than ZnO and WO3 nanowires. The response (RCl2/Rair) of the SnO2 nanowire sensor to 50 ppb Cl2 at 50 degrees C was about 57. Hence, SnO2 nanowires can be an excellent sensing material for detecting Cl2 gas at the ppb level under low temperatures. Abnormal sensing characteristics were observed in the WO3 and SnO2 nanowire sensors at certain temperatures; in particular, the response level of these sensors to 5 ppm of Cl2 was lower than that to 2.5 ppm of Cl2. The sensing mechanism of the SnO2 nanowire sensor was also elucidated by determining Cl2 responses under N2 and dry air as carrier gases. We proved that the Cl2 molecule was first directly adsorbed on the metal oxide surface and was then substituted for pre-adsorbed oxygen, followed by lattice oxygen. PMID- 26816342 TI - Enhancement of Nutraceutical Bioavailability using Excipient Nanoemulsions: Role of Lipid Digestion Products on Bioaccessibility of Carotenoids and Phenolics from Mangoes. AB - The ability of excipient nanoemulsions to increase the bioaccessibility of different kinds of nutraceuticals (phenolics and carotenoids) in mangoes was studied. Oil-in-water excipient nanoemulsions containing small digestible lipid nanoparticles (d < 200 nm) were prepared using different oil phases: medium chain triglycerides (MCT) and long-chain triglycerides (LCT). These nanoemulsions were then mixed with pureed mango and passed through a simulated gastrointestinal tract (GIT): mouth, stomach, and small intestine. Carotenoid bioaccessibility decreased in the following order: LCT nanoemulsions > MCT nanoemulsions > buffer solution, which was attributed to differences in the solubilization capacity of the mixed micelles generated in the intestinal fluids. The digestion products of LCT formed mixed micelles with hydrophobic domains large enough to accommodate the carotenoids, whereas those of MCT did not. Excipient emulsions had much less effect on phenolic bioaccessibility, which may be because phenolics are smaller more polar molecules and are therefore more easily solubilized in aqueous intestinal fluids. These results highlight the potential of excipient nanoemulsions in boosting the bioavailability of lipophilic bioactive agents in fruits and vegetables. PMID- 26816343 TI - Phosphorylation and Activation of RhoA by ERK in Response to Epidermal Growth Factor Stimulation. AB - The small GTPase RhoA has been implicated in various cellular activities, including the formation of stress fibers, cell motility, and cytokinesis. In addition to the canonical GTPase cycle, recent findings have suggested that phosphorylation further contributes to the tight regulation of Rho GTPases. Indeed, RhoA is phosphorylated on serine 188 (188S) by a number of protein kinases. We have recently reported that Rac1 is phosphorylated on threonine 108 (108T) by extracellular signal-regulated kinases (ERK) in response to epidermal growth factor (EGF) stimulation. Here, we provide evidence that RhoA is phosphorylated by ERK on 88S and 100T in response to EGF stimulation. We show that ERK interacts with RhoA and that this interaction is dependent on the ERK docking site (D-site) at the C-terminus of RhoA. EGF stimulation enhanced the activation of the endogenous RhoA. The phosphomimetic mutant, GFP-RhoA S88E/T100E, when transiently expressed in COS-7 cells, displayed higher GTP binding than wild type RhoA. Moreover, the expression of GFP-RhoA S88E/T100E increased actin stress fiber formation in COS-7 cells, which is consistent with its higher activity. In contrast to Rac1, phosphorylation of RhoA by ERK does not target RhoA to the nucleus. Finally, we show that regardless of the phosphorylation status of RhoA and Rac1, substitution of the RhoA PBR with the Rac1 PBR targets RhoA to the nucleus and substitution of Rac1 PBR with RhoA PBR significantly reduces the nuclear localization of Rac1. In conclusion, ERK phosphorylates RhoA on 88S and 100T in response to EGF, which upregulates RhoA activity. PMID- 26816345 TI - Eye Tracking Reveals Impaired Attentional Disengagement Associated with Sensory Response Patterns in Children with Autism. AB - This study used a gap-overlap paradigm to examine the impact of distractor salience and temporal overlap on the ability to disengage and orient attention in 50 children (4-13 years) with ASD, DD and TD, and associations between attention and sensory response patterns. Results revealed impaired disengagement and orienting accuracy in ASD. Disengagement was impaired across all groups during temporal overlap for dynamic stimuli compared to static, but only ASD showed slower disengagement from multimodal relative to unimodal dynamic stimuli. Attentional disengagement had differential associations with distinct sensory response patterns in ASD and DD. Atypical sensory processing and temporal binding appear to be intertwined with development of disengagement in ASD, but longitudinal studies are needed to unravel causal pathways. PMID- 26816344 TI - The Cellular Thioredoxin-1/Thioredoxin Reductase-1 Driven Oxidoreduction Represents a Chemotherapeutic Target for HIV-1 Entry Inhibition. AB - BACKGROUND: The entry of HIV into its host cell is an interesting target for chemotherapeutic intervention in the life-cycle of the virus. During entry, reduction of disulfide bridges in the viral envelope glycoprotein gp120 by cellular oxidoreductases is crucial. The cellular thioredoxin reductase-1 plays an important role in this oxidoreduction process by recycling electrons to thioredoxin-1. Therefore, thioredoxin reductase-1 inhibitors may inhibit gp120 reduction during HIV-1 entry. In this present study, tellurium-based thioredoxin reductase-1 inhibitors were investigated as potential inhibitors of HIV entry. RESULTS: The organotellurium compounds inhibited HIV-1 and HIV-2 replication in cell culture at low micromolar concentrations by targeting an early event in the viral infection cycle. Time-of-drug-addition studies pointed to virus entry as the drug target, more specifically: the organotellurium compound TE-2 showed a profile similar or close to that of the fusion inhibitor enfuvirtide (T-20). Surface plasmon resonance-based interaction studies revealed that the compounds do not directly interact with the HIV envelope glycoproteins gp120 and gp41, nor with soluble CD4, but instead, dose-dependently bind to thioredoxin reductase-1. By inhibiting the thioredoxin-1/thioredoxin reductase-1-directed oxidoreduction of gp120, the organotellurium compounds prevent conformational changes in the viral glycoprotein which are necessary during viral entry. CONCLUSION: Our findings revealed that thioredoxin-1/thioredoxin reductase-1 acts as a cellular target for the inhibition of HIV entry. PMID- 26816346 TI - Inhibition of CaMKII Attenuates Progressing Disruption of Ca(2+) Homeostasis Upon Left Ventricular Assist Device Implantation in Human Heart Failure. AB - In heart failure, left ventricular assist device (LVAD) implantation is performed to ensure sufficient cardiac output. Whereas some patients are subsequently weaned from LVAD support, other patients still need heart transplantation. To elucidate underlying mechanisms, we assessed the arrhythmogenic SR-Ca(2+) leak at the time of LVAD implantation (HF-Im) and heart transplantation (HF-Tx) and evaluated the effects of CaMKII-inhibition. Human left-ventricular cardiomyocytes were isolated, paced at 1 Hz for 10 beats to ensure SR-Ca(2+) loading and scanned for diastolic Ca(2+) sparks (confocal microscopy). In HF-Im, the high diastolic spark frequency (CaSpF) of 0.76 +/- 0.12 * 100 MUm(-1) * s(-1) could be reduced to 0.48 +/- 0.10 * 100 MUm(-1) * s(-1) by CaMKII inhibition (AIP, 1 MUM). The amplitude of Ca(2+) sparks, width, and length was not significantly altered. In sum, CaMKII inhibition yielded a clear tendency toward a reduction of the SR Ca(2+) leak (n cells/patients = 76/6 vs. 108/6, P = 0.08). In HF-Tx, we detected an even higher CaSpF of 1.00 +/- 0.10 100 MUm(-1) * s(-1) and a higher SR-Ca(2+) leak compared with HF-Im (increase by 81 +/- 33%, n cells/patients = 156/7 vs. 130/7, P < 0.05), which fits to the further decreased LV function. Here, CaMKII inhibition likewise reduced CaSpF (0.35 +/- 0.09 100 MUm(-1) * s(-1,) P = 0.06) and significantly reduced spark duration (n sparks/patients = 58/3 vs. 159/3, P < 0.05). Conclusively, the SR-Ca(2+) leak was reduced by 69 +/- 12% in HF-Tx upon CaMKII inhibition (n cells/patients = 53/3 vs. 91/3, P < 0.05). These data show that the SR-Ca(2+) leak correlates with the development of LV function after LVAD implantation and may represent an important pathomechanism. The fact that CaMKII inhibition reduces the SR-Ca(2+) leak in HF-Tx suggests that CaMKII inhibition may be a promising option to beneficially influence clinical course after LVAD implantation. PMID- 26816347 TI - Cu2Se and Cu Nanocrystals as Local Sources of Copper in Thermally Activated In Situ Cation Exchange. AB - Among the different synthesis approaches to colloidal nanocrystals, a recently developed toolkit is represented by cation exchange reactions, where the use of template nanocrystals gives access to materials that would be hardly attainable via direct synthesis. Besides, postsynthetic treatments, such as thermally activated solid-state reactions, represent a further flourishing route to promote finely controlled cation exchange. Here, we report that, upon in situ heating in a transmission electron microscope, Cu2Se or Cu nanocrystals deposited on an amorphous solid substrate undergo partial loss of Cu atoms, which are then engaged in local cation exchange reactions with Cu "acceptor" phases represented by rod- and wire-shaped CdSe nanocrystals. This thermal treatment slowly transforms the initial CdSe nanocrystals into Cu(2-x)Se nanocrystals, through the complete sublimation of Cd and the partial sublimation of Se atoms. Both Cu "donor" and "acceptor" particles were not always in direct contact with each other; hence, the gradual transfer of Cu species from Cu2Se or metallic Cu to CdSe nanocrystals was mediated by the substrate and depended on the distance between the donor and acceptor nanostructures. Differently from what happens in the comparably faster cation exchange reactions performed in liquid solution, this study shows that slow cation exchange reactions can be performed at the solid state and helps to shed light on the intermediate steps involved in such reactions. PMID- 26816349 TI - Interaction of the Alzheimer Abeta(25-35) peptide segment with model membranes. AB - Alzheimer's disease is characterized by the presence of amyloid plaques in the brain. The main components of these plaques are the Abeta(1-40) and Abeta(1-42) peptides but the Abeta(25-35) sequence is the most frequently studied fragment because it represents a biologically active region of the longer Abeta peptides. In the present work, the interactions of Abeta(25-35) peptide with model membranes were investigated, taking into consideration the aggregation state of the peptide. Monolayers and liposomes were taken as model membranes with two lipid compositions: the equimolar ternary mixture of 1-palmitoyl-2-oleoyl-sn glycero-3-phosphocholine (POPC), sphingomyelin (SM), and cholesterol (Chol) and the equimolar POPC/SM binary mixture. The interaction of Abeta(25-35) with the monolayers, investigated at low concentrations (0.25-4MUM), suggested a three step mechanism: adsorption-monomers or dimers adsorb at the polar region of the lipid monolayer; nucleation-adsorbed peptides act as nucleation sites for higher aggregates; and penetration-these aggregates insert in the hydrophobic region of the monolayer. Chol slightly enhances the peptide-lipid monolayer interaction. The large aggregates nucleated in the bulk solution evidenced a weak interaction with monolayers. The interaction of Abeta(25-35) with liposomes, followed by a Quartz Crystal Microbalance with Dissipation (QCM-D) in a large range of peptide concentrations (10-80MUM), was very small, independently of the peptide concentration. PMID- 26816348 TI - Lecithin-gold hybrid nanocarriers as efficient and pH selective vehicles for oral delivery of diacerein-In-vitro and in-vivo study. AB - We report the synthesis and evaluation of lecithin-gold hybrid nanocarriers for the oral delivery of drugs with improved pharmacokinetics, Au-drug interactive bioactivity and controlled drug releasing behavior at physiological pH inside human body. For this purpose, diacerein, a hydrophobic anti-arthritic drug, was loaded in lecithin NPs (LD NPs), which were further coated by Au NPs either by in situ production of Au NPs on LD NPs or by employing pre-synthesized Au NPs. All LDAu NPs were found to release drug selectively at the physiological pH of 7.4 and showed 2.5 times increase in the oral bioavailability of diacerein. Pharmacological efficacy was significantly improved i.e., greater than the additive effect of diacerein and Au NPs alone. LDAu NPs started suppressing inflammation at first phase, whereas LD NPs showed activity in the second phase of inflammation. These results indicate the interaction of Au NPs with prostaglandins and histaminic mediators of first phase of carrageenan induced inflammation. Acute toxicity study showed no hepatic damage but the renal toxicity parameters were close to the upper safety limits. Toxicity parameters were dependent on surface engineering of LDAu NPs. Apart from enhancing the oral bioavailability of hydrophobic drugs and improving their anti-inflammatory activity, these hybrid nanocarriers may have potential applications in gold-based photothermal therapy and the tracing of inflammation at atherosclerotic and arthritic site. PMID- 26816350 TI - Health conditions associated with metabolic syndrome after cancer at a young age: A nationwide register-based study. AB - PURPOSE: Childhood cancer survivors are at risk for developing metabolic syndrome (MetS), which subsequently leads to cardiovascular morbidity and excess mortality. Our aim was to investigate the purchases of medications associated with MetS among 7551 early onset cancer patients compared to siblings. METHODS: Our nationwide Finnish population-based registry study analyzed the drug purchase of medication among early onset cancer patients diagnosed with cancer below the age of 35 years between 1994 and 2004 compared to siblings by linkage to the drug purchase registry, allowing for a maximal follow-up of 18 years. RESULTS: The hazard ratios (HRs) for purchasing antihypertensives and diabetes drugs were higher after both childhood (HR 4.6, 95%CI 3.1-7.0; HR 3.0, 95%1.5-6.1) and young adulthood (YA) cancer (HR 1.5, 95%CI 1.3-1.8; HR 1.6, 95%CI 1.1-2.2) compared to siblings. The HRs for purchasing lipid-lowering drugs were elevated both after childhood (HR 4.3,95%CI 0.9-19.5) and YA cancer (HR 1.6, 95%CI 1.04-2.5), but only reached significance in YA cancer patients. Among specific cancer diagnosis groups, highest HR values for antihypertensives were found in childhood acute lymphoblastic leukemia (ALL) (HR 6.1, 95%CI 3.7-10.3) and bone tumor (HR 4.3, 95%CI 1.9-9.4), and YA ALL (HR 4.8, 95%CI 3.1-7.0) and acute myeloid leukemia (AML) (HR 3.4, 95%CI 2.5-5.1) patients. Moreover, childhood ALL (HR 6.3, 95%CI 2.7-14.8), AML (HR 7.6, 95%CI 1.9-24.5) and central nervous system (CNS)-tumor (HR 3.5, 95%CI 1.3-9.2) and YA ALL (HR 3.7, 95%CI 1.2-9.5) patients showed the strongest likelihood of purchasing diabetes drugs compared to siblings. CONCLUSION: The purchase of medications associated with MetS was increased after early onset cancer and highly dependent on the age at cancer diagnosis and the cancer diagnosis. Prevention strategies are imperative for reducing potentially life-threatening cardiovascular complications after early onset cancer. PMID- 26816352 TI - Empowering great teachers. PMID- 26816351 TI - ABCC2 polymorphisms and survival in the Princess Margaret cohort study and the NCIC clinical trials group BR.24 trial of platinum-treated advanced stage non small cell lung cancer patients. AB - BACKGROUND: The drug transporter ABCC2 is upregulated in non-small cell lung cancer (NSCLC) and implicated in platinum resistance. We evaluated the association between germline polymorphisms in the ABCC2 gene and survival outcomes of platinum-treated advanced NSCLC patients. MATERIAL AND METHODS: Ten candidate and tagging germline polymorphisms in the ABCC2 gene were genotyped in a discovery cohort of 170 platinum-treated stage IV NSCLC patients from the Princess Margaret Cancer Centre. Associations with overall survival were assessed using multivariate Cox proportional hazard models adjusted for prognostic variables. To validate our results, we analyzed the association of the two top polymorphisms in the ABCC2 gene on survival outcomes of 219 stage IIIB-IV NSCLC patients enrolled on the NCIC Clinical Trials Group BR.24 clinical trial. RESULTS: Only one polymorphism was validated across both cohorts for an association with overall survival: the A allele of the ABCC2 polymorphism, rs8187710 (4544G>A), was associated with adverse overall survival (adjusted hazard ratio [aHR] 2.22; 95% CI: 1.2-4.0; p=0.009) among our stage IV NSCLC patients. A significant association with overall survival (aHR 1.73; 95% CI: 1.0 2.9; p=0.036) was observed for the same ABCC2 polymorphism in the BR.24 validation cohort. No other ABCC2 polymorphisms were associated with outcome. CONCLUSION: The ABCC2 polymorphism, rs8187710 (4544G>A), is associated with overall survival in platinum-treated advanced NSCLC patients. Additional studies are needed to evaluate the predictive versus prognostic nature of this relationship, and to explore the functional effect of this polymorphism on the pharmacokinetics of platinum drugs. PMID- 26816354 TI - Space. Astronomers see ashes of the first stars. PMID- 26816355 TI - Neuroscience. Regulators seek to tame brain training's 'Wild West'. PMID- 26816356 TI - Scientific publishing. Publishers embrace scheme to end name confusion. PMID- 26816358 TI - Technology. Incandescent lights go green. PMID- 26816357 TI - Comparative biology. Female organs revealed as weapons in sexual arms race. PMID- 26816360 TI - The social life of quarks. PMID- 26816361 TI - A nation divided. PMID- 26816359 TI - Scientific community. Caltech suspends professor for harassment. PMID- 26816362 TI - Infectious disease. Adapting Koch's postulates. PMID- 26816363 TI - RNA. Small peptides control heart activity. PMID- 26816364 TI - Genetics. IRES unplugged. PMID- 26816365 TI - Applied optics. Tuning terahertz lasers via graphene plasmons. PMID- 26816366 TI - Planetary science. Sampling the Moon's atmosphere. PMID- 26816368 TI - Visa rules imperil collaboration. PMID- 26816367 TI - Weather stations lack forest data. PMID- 26816369 TI - Mechanistic biological modeling thrives. PMID- 26816370 TI - Comment on "Broken translational and rotational symmetry via charge stripe order in underdoped YBa2Cu3O6+y". AB - Comin et al. (Reports, 20 March 2015, p. 1335) have interpreted their resonant x ray scattering experiment as indicating that charge inhomogeneities in the family of high-temperature superconductors YBa2Cu3O6+y (YBCO) have the character of one dimensional stripes rather than two-dimensional checkerboards. The present Comment shows that one cannot distinguish between stripes and checkerboards on the basis of the above experiment. PMID- 26816371 TI - Response to Comment on "Broken translational and rotational symmetry via charge stripe order in underdoped YBa2Cu3O6+y". AB - Fine questions our interpretation of unidirectional stripes over a bidirectional checkerboard and illustrates his criticism by simulating a momentum space structure consistent with our data and corresponding to a checkerboard-looking real space density. Here, we use a local rotational-symmetry analysis to demonstrate that the simulated image is actually composed of locally unidirectional modulations of the charge density, consistent with our original conclusions. PMID- 26816373 TI - Applied optics. Gain modulation by graphene plasmons in aperiodic lattice lasers. AB - Two-dimensional graphene plasmon-based technologies will enable the development of fast, compact, and inexpensive active photonic elements because, unlike plasmons in other materials, graphene plasmons can be tuned via the doping level. Such tuning is harnessed within terahertz quantum cascade lasers to reversibly alter their emission. This is achieved in two key steps: first, by exciting graphene plasmons within an aperiodic lattice laser and, second, by engineering photon lifetimes, linking graphene's Fermi energy with the round-trip gain. Modal gain and hence laser spectra are highly sensitive to the doping of an integrated, electrically controllable, graphene layer. Demonstration of the integrated graphene plasmon laser principle lays the foundation for a new generation of active, programmable plasmonic metamaterials with major implications across photonics, material sciences, and nanotechnology. PMID- 26816372 TI - Organic chemistry. Strain-release amination. AB - To optimize drug candidates, modern medicinal chemists are increasingly turning to an unconventional structural motif: small, strained ring systems. However, the difficulty of introducing substituents such as bicyclo[1.1.1]pentanes, azetidines, or cyclobutanes often outweighs the challenge of synthesizing the parent scaffold itself. Thus, there is an urgent need for general methods to rapidly and directly append such groups onto core scaffolds. Here we report a general strategy to harness the embedded potential energy of effectively spring loaded C-C and C-N bonds with the most oft-encountered nucleophiles in pharmaceutical chemistry, amines. Strain-release amination can diversify a range of substrates with a multitude of desirable bioisosteres at both the early and late stages of a synthesis. The technique has also been applied to peptide labeling and bioconjugation. PMID- 26816374 TI - Organic chemistry. Functionalization of C(sp3)-H bonds using a transient directing group. AB - Proximity-driven metalation has been extensively exploited to achieve reactivity and selectivity in carbon-hydrogen (C-H) bond activation. Despite the substantial improvement in developing more efficient and practical directing groups, their stoichiometric installation and removal limit efficiency and, often, applicability as well. Here we report the development of an amino acid reagent that reversibly reacts with aldehydes and ketones in situ via imine formation to serve as a transient directing group for activation of inert C-H bonds. Arylation of a wide range of aldehydes and ketones at the beta or gamma positions proceeds in the presence of a palladium catalyst and a catalytic amount of amino acid. The feasibility of achieving enantioselective C-H activation reactions using a chiral amino acid as the transient directing group is also demonstrated. PMID- 26816375 TI - Astronomy. ASASSN-15lh: A highly super-luminous supernova. AB - We report the discovery of ASASSN-15lh (SN 2015L), which we interpret as the most luminous supernova yet found. At redshift z = 0.2326, ASASSN-15lh reached an absolute magnitude of Mu ,AB = -23.5 +/- 0.1 and bolometric luminosity Lbol = (2.2 +/- 0.2) * 10(45) ergs s(-1), which is more than twice as luminous as any previously known supernova. It has several major features characteristic of the hydrogen-poor super-luminous supernovae (SLSNe-I), whose energy sources and progenitors are currently poorly understood. In contrast to most previously known SLSNe-I that reside in star-forming dwarf galaxies, ASASSN-15lh appears to be hosted by a luminous galaxy (MK ~ -25.5) with little star formation. In the 4 months since first detection, ASASSN-15lh radiated (1.1 +/- 0.2) * 10(52) ergs, challenging the magnetar model for its engine. PMID- 26816376 TI - Paleoanthropology. Early human presence in the Arctic: Evidence from 45,000-year old mammoth remains. AB - Archaeological evidence for human dispersal through northern Eurasia before 40,000 years ago is rare. In west Siberia, the northernmost find of that age is located at 57 degrees N. Elsewhere, the earliest presence of humans in the Arctic is commonly thought to be circa 35,000 to 30,000 years before the present. A mammoth kill site in the central Siberian Arctic, dated to 45,000 years before the present, expands the populated area to almost 72 degrees N. The advancement of mammoth hunting probably allowed people to survive and spread widely across northernmost Arctic Siberia. PMID- 26816377 TI - Neural circuits. Inhibition protects acquired song segments during vocal learning in zebra finches. AB - Vocal imitation involves incorporating instructive auditory information into relevant motor circuits through processes that are poorly understood. In zebra finches, we found that exposure to a tutor's song drives spiking activity within premotor neurons in the juvenile, whereas inhibition suppresses such responses upon learning in adulthood. We measured inhibitory currents evoked by the tutor song throughout development while simultaneously quantifying each bird's learning trajectory. Surprisingly, we found that the maturation of synaptic inhibition onto premotor neurons is correlated with learning but not age. We used synthetic tutoring to demonstrate that inhibition is selective for specific song elements that have already been learned and not those still in refinement. Our results suggest that structured inhibition plays a crucial role during song acquisition, enabling a piece-by-piece mastery of complex tasks. PMID- 26816378 TI - A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle. AB - Muscle contraction depends on release of Ca(2+) from the sarcoplasmic reticulum (SR) and reuptake by the Ca(2+)adenosine triphosphatase SERCA. We discovered a putative muscle-specific long noncoding RNA that encodes a peptide of 34 amino acids and that we named dwarf open reading frame (DWORF). DWORF localizes to the SR membrane, where it enhances SERCA activity by displacing the SERCA inhibitors, phospholamban, sarcolipin, and myoregulin. In mice, overexpression of DWORF in cardiomyocytes increases peak Ca(2+) transient amplitude and SR Ca(2+) load while reducing the time constant of cytosolic Ca(2+) decay during each cycle of contraction-relaxation. Conversely, slow skeletal muscle lacking DWORF exhibits delayed Ca(2+) clearance and relaxation and reduced SERCA activity. DWORF is the only endogenous peptide known to activate the SERCA pump by physical interaction and provides a means for enhancing muscle contractility. PMID- 26816379 TI - Metabolism. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress. AB - Mitochondria undergo fragmentation in response to electron transport chain (ETC) poisons and mitochondrial DNA-linked disease mutations, yet how these stimuli mechanistically connect to the mitochondrial fission and fusion machinery is poorly understood. We found that the energy-sensing adenosine monophosphate (AMP) activated protein kinase (AMPK) is genetically required for cells to undergo rapid mitochondrial fragmentation after treatment with ETC inhibitors. Moreover, direct pharmacological activation of AMPK was sufficient to rapidly promote mitochondrial fragmentation even in the absence of mitochondrial stress. A screen for substrates of AMPK identified mitochondrial fission factor (MFF), a mitochondrial outer-membrane receptor for DRP1, the cytoplasmic guanosine triphosphatase that catalyzes mitochondrial fission. Nonphosphorylatable and phosphomimetic alleles of the AMPK sites in MFF revealed that it is a key effector of AMPK-mediated mitochondrial fission. PMID- 26816380 TI - RNA biochemistry. Transcriptome-wide distribution and function of RNA hydroxymethylcytosine. AB - Hydroxymethylcytosine, well described in DNA, occurs also in RNA. Here, we show that hydroxymethylcytosine preferentially marks polyadenylated RNAs and is deposited by Tet in Drosophila. We map the transcriptome-wide hydroxymethylation landscape, revealing hydroxymethylcytosine in the transcripts of many genes, notably in coding sequences, and identify consensus sites for hydroxymethylation. We found that RNA hydroxymethylation can favor mRNA translation. Tet and hydroxymethylated RNA are found to be most abundant in the Drosophila brain, and Tet-deficient fruitflies suffer impaired brain development, accompanied by decreased RNA hydroxymethylation. This study highlights the distribution, localization, and function of cytosine hydroxymethylation and identifies central roles for this modification in Drosophila. PMID- 26816382 TI - My adviser's best advice. PMID- 26816381 TI - Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin. AB - Genes encoding human beta-type globin undergo a developmental switch from embryonic to fetal to adult-type expression. Mutations in the adult form cause inherited hemoglobinopathies or globin disorders, including sickle cell disease and thalassemia. Some experimental results have suggested that these diseases could be treated by induction of fetal-type hemoglobin (HbF). However, the mechanisms that repress HbF in adults remain unclear. We found that the LRF/ZBTB7A transcription factor occupies fetal gamma-globin genes and maintains the nucleosome density necessary for gamma-globin gene silencing in adults, and that LRF confers its repressive activity through a NuRD repressor complex independent of the fetal globin repressor BCL11A. Our study may provide additional opportunities for therapeutic targeting in the treatment of hemoglobinopathies. PMID- 26816383 TI - Comparative genetics. Systematic discovery of cap-independent translation sequences in human and viral genomes. AB - To investigate gene specificity at the level of translation in both the human genome and viruses, we devised a high-throughput bicistronic assay to quantify cap-independent translation. We uncovered thousands of novel cap-independent translation sequences, and we provide insights on the landscape of translational regulation in both humans and viruses. We find extensive translational elements in the 3' untranslated region of human transcripts and the polyprotein region of uncapped RNA viruses. Through the characterization of regulatory elements underlying cap-independent translation activity, we identify potential mechanisms of secondary structure, short sequence motif, and base pairing with the 18S ribosomal RNA (rRNA). Furthermore, we systematically map the 18S rRNA regions for which reverse complementarity enhances translation. Thus, we make available insights into the mechanisms of translational control in humans and viruses. PMID- 26816385 TI - Smoking cessation advice for people with serious mental illness. AB - BACKGROUND: People with a serious mental illness are more likely to smoke more and to be more dependent smokers than the general population. This may be due to a wide range of factors that could include a common aetiology to both smoking and the illness, self medication, smoking to alleviate adverse effects of medications, boredom in the existing environment, or a combination of these factors. It is important to undertake this review to facilitate improvements in both the health and safety of people with serious mental illness who smoke, and to reduce the overall burden of costs (both financial and health) to the smoker and, eventually, to the taxpayer. OBJECTIVES: To review the effects of smoking cessation advice for people with serious mental illness. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Specialized Trials Register up to 2 April 2015, which is based on regular searches of CENTRAL, BIOSIS, PubMed, MEDLINE, EMBASE, CINAHL, PsycINFO, and trial registries. We also undertook unsystematic searches of a sample of the component databases (BNI, CINHAL, EMBASE, MEDLINE, and PsycINFO), up to 2 April 2015, and searched references of all identified studies SELECTION CRITERIA: We planned to include all randomised controlled trials (RCTs) that focussed on smoking cessation advice versus standard care or comparing smoking cessation advice with other more focussed methods of delivering care or information. DATA COLLECTION AND ANALYSIS: The review authors (PK, AC, and DB) independently screened search results but did not identify any trials that fulfilled the inclusion criteria of this review. MAIN RESULTS: We did not identify any RCTs that evaluated advice regarding smoking cessation for people with serious mental illness. The excluded studies illustrate that randomisation of packages of care relevant to smokers with serious mental illness is possible. AUTHORS' CONCLUSIONS: People with serious mental illness are more likely to smoke than the general population. Yet we could not find any high quality evidence to guide the smoking cessation advice healthcare professionals pass onto service users. This is an area where trials are possible and needed. PMID- 26816384 TI - Viral immunity. Transkingdom control of viral infection and immunity in the mammalian intestine. AB - Viruses that infect the intestine include major human pathogens (retroviruses, noroviruses, rotaviruses, astroviruses, picornaviruses, adenoviruses, herpesviruses) that constitute a serious public health problem worldwide. These viral pathogens are members of a large, complex viral community inhabiting the intestine termed "the enteric virome." Enteric viruses have intimate functional and genetic relationships with both the host and other microbial constituents that inhabit the intestine, such as the bacterial microbiota, their associated phages, helminthes, and fungi, which together constitute the microbiome. Emerging data indicate that enteric viruses regulate, and are in turn regulated by, these other microbes through a series of processes termed "transkingdom interactions." This represents a changing paradigm in intestinal immunity to viral infection. Here we review recent advances in the field and propose new ways in which to conceptualize this important area. PMID- 26816387 TI - Pulsed electron-electron double resonance, peptaibols and chlorotoxin in review. PMID- 26816386 TI - Tuning the Range of Polyacrylamide Gel Stiffness for Mechanobiology Applications. AB - Adjusting the acrylamide monomer and cross-linker content in polyacrylamide gels controls the hydrogel stiffness, yet the reported elastic modulus for the same formulations varies widely and these discrepancies are frequently attributed to different measurement methods. Few studies exist that examine stiffness trends across monomer and cross-linker concentrations using the same characterization platform. In this work, we use Atomic Force Microscopy and analyze force-distance curves to derive the elastic modulus of polyacrylamide hydrogels. We find that gel elastic modulus increases with increasing cross-link concentration until an inflection point, after which gel stiffness decreases with increasing cross linking. This behavior arises because of the formation of highly cross-linked clusters, which add inhomogeneity and heterogeneity to the network structure, causing the global network to soften even under high cross-linking conditions. We identify these inflection points for three different total polymer formulations. When we alter gelation kinetics by using a low polymerization temperature, we find that gels are stiffer when polymerized at 4 degrees C compared to room temperature, indicating a complex relationship between gel structure, elasticity, and network formation. We also investigate how gel stiffness changes during storage over 10 days and find that specific gel formulations undergo significant stiffening (1.55 +/- 0.13), which may be explained by differences in gel swelling resulting from initial polymerization parameters. Taken together, our study emphasizes the importance of polyacrylamide formulation, polymerization temperature, gelation time, and storage duration in defining the structural and mechanical properties of the polyacrylamide hydrogels. PMID- 26816388 TI - Monitoring Physical and Cognitive Overload During a Training Camp in Professional Female Cyclists. AB - PURPOSE: High training loads combined with other stressors can lead to performance decrements. The time needed to recover determines the diagnosis of (non)-functional overreaching or the overtraining syndrome. The aim of this study was to describe the effects of an 8-day (intensified) training camp of professional female cyclists on physical and cognitive performance. METHODS: Nine subjects performed a 30-min time trial (TT), cognitive test, and Profile of Mood States questionnaire before, during, and after a training camp (49% increased training volume). On data collection, cyclists were classified as "overreached" (OR) or "adapted" (A) based on TT performance. Two-way repeated-measures analysis of variance was used to detect changes in physical and cognitive parameters. RESULTS: Five cyclists were described as OR based on decreased mean power output (MPO) (-7.03%) on day 8. Four cyclists were classified as A (increased MPO: +1.72%). MPO and maximal heart rate were significantly different between A and OR groups. A significant slower reaction time (RT) (+3.35%) was found in OR subjects, whereas RT decreased (-4.59%) in A subjects. The change in MPO was negatively correlated with change in RT in the cognitive test (R2 = .52). CONCLUSIONS: This study showed that the use of objective, inexpensive, and easy to-interpret physical and cognitive tests can facilitate the monitoring of training adaptations in professional female athletes. PMID- 26816389 TI - Evaluating Warm-Up Strategies for Elite Sprint Breaststroke Swimming Performance. AB - PURPOSE: Targeted passive heating and completion of dryland-based activation exercises within the warm-up can enhance sprint freestyle performance. The authors investigated if these interventions would also elicit improvements in sprint breaststroke swimming performance. METHODS: Ten national and internationally competitive swimmers (~805 FINA (Federation internationale de natation) 2014 scoring points; 6 men, mean +/- SD 20 +/- 1 y; 4 women, 21 +/- 3 y) completed a standardized pool warm-up (1550 m) followed by a 30-min transition phase and a 100-m breaststroke time trial. In the transition phase, swimmers wore a conventional tracksuit and remained seated (control) or wore tracksuit pants with integrated heating elements and performed a 5-min dryland-based exercise routine (combo) in a crossover design. RESULTS: Performance in the 100-m time trial (control: 68.6 +/- 4.0 s, combo: 68.4 +/- 3.9 s, P = .55) and start times to 15 m (control: 7.3 +/- 0.6 s; combo: 7.3 +/- 0.6 s; P = .81) were not different between conditions. It was unclear (P = .36) whether combo (-0.12 degrees C +/- 0.19 degrees C [mean +/- 90% confidence limits]) elicited an improvement in core temperature maintenance in the transition phase compared with control (-0.31 degrees C +/- 0.19 degrees C). Skin temperature immediately before commencement of the time trial was higher (by ~1 degrees C, P = .01) within combo (30.13 degrees C +/- 0.88 degrees C [mean +/- SD]) compared with control (29.11 degrees C +/- 1.20 degrees C). Lower-body power output was not different between conditions before the time trial. CONCLUSIONS: Targeted passive heating and completion of dryland-based activation exercises in the transition phase does not enhance sprint breaststroke performance despite eliciting elevated skin temperature immediately before time trial commencement. PMID- 26816390 TI - Tracking Morning Fatigue Status Across In-Season Training Weeks in Elite Soccer Players. AB - PURPOSE: To quantify the mean daily changes in training and match load and any parallel changes in indicators of morningmeasured fatigue across in-season training weeks in elite soccer players. METHODS: After each training session and match (TL), session ratings of perceived exertion (s-RPE) were recorded to calculate overall session load (RPE-TL) in 29 English Premier League players from the same team. Morning ratings of fatigue, sleep quality, and delayed-onset muscle soreness (DOMS), as well as submaximal exercise heart rate (HRex), postexercise heart-rate recovery (HRR%), and heart-rate variability (HRV) were recorded before match day and 1, 2, and 4 d postmatch. Data were collected for a median duration of 3 wk (range 1-13) and reduced to a typical weekly cycle including no midweek match and a weekend match day. Data were analyzed using withinsubject linear mixed models. RESULTS: RPE-TL was approximately 600 arbitrary units (AU) (95% confidence interval 546-644) higher on match day than following day (P < .001). RPE-TL progressively decreased by "60 AU per day over the 3 days before a match (P < .05). Morning-measured fatigue, sleep quality, and DOMS tracked the changes in RPE-TL, being 35-40% worse on postmatch day vs prematch day (P < .001). Perceived fatigue, sleep quality, and DOMS improved by 17-26% from postmatch day to 3 d postmatch, with further smaller (7%-14%) improvements occurring between 4 d postmatch and prematch day (P < .01). There were no substantial or statistically significant changes in HRex, HRR%, or HRV over the weekly cycle (P > .05). CONCLUSIONS: Morning-measured ratings of fatigue, sleep quality, and DOMS are clearly more sensitive than HR-derived indices to the daily fluctuations in session load experienced by elite soccer players in a standard in-season week. PMID- 26816391 TI - Relationship Between External and Internal Loads of Professional Soccer Players During Full Matches in Official Games Using Global Positioning Systems and Heart Rate Technology. AB - PURPOSE: To analyze the match running profile, distance traveled over successive 15 min of match play, heart rates (HRs), and index of performance efficiency (effindex) of professional soccer players with a global positioning system (GPS) and HR in official competition. METHODS: Twenty-six professional players were investigated during full matches in competitive club-level matches (N = 223). Time-motion data and HR were collected using GPS and HR technology. RESULTS: The relative total distance was 113 +/- 11 m/min, with substantial differences between halves. For all playing positions, a substantial decrease in total distance and distance covered at >13.0 km/h was observed in the second half in comparison with the first. The decrease during the second half in distance covered at >13.0 km/h was substantially higher than in total distance. The average HR recorded was 86.0% maximal HR, and the relationship between external and internal load (effindex) was 1.3, with substantial differences between halves in all playing positions, except strikers for effindex. Wide midfielders reflected substantially the lowest mean HR and highest effindex, whereas center backs showed substantially the lowest effindex of all playing positions. CONCLUSIONS: The current study confirmed the decrement in a player's performance toward the end of a match in all playing positions. Wide midfielders displayed the highest and fittest levels of physical and physiological demands, respectively, whereas center backs had the lowest and least-fit levels of physical and physiological demands, respectively. The position-specific relationship between external and internal load confirms that players with more overall running performance during the full match were the best in effindex. PMID- 26816392 TI - Multiscale modeling biological systems. PMID- 26816393 TI - Crosstalk between pathways enhances the controllability of signalling networks. AB - The control of complex networks is one of the most challenging problems in the fields of biology and engineering. In this study, the authors explored the controllability and control energy of several signalling networks, which consisted of many interconnected pathways, including networks with a bow-tie architecture. On the basis of the theory of structure controllability, they revealed that biological mechanisms, such as cross-pathway interactions, compartmentalisation and so on make the networks easier to fully control. Furthermore, using numerical simulations for two realistic examples, they demonstrated that the control energy of normal networks with crosstalk is lower than in networks without crosstalk. These results indicate that the biological networks are optimally designed to achieve their normal functions from the viewpoint of the control theory. The authors' work provides a comprehensive understanding of the impact of network structures and properties on controllability. PMID- 26816394 TI - Model reduction and parameter estimation of non-linear dynamical biochemical reaction networks. AB - Parameter estimation for high dimension complex dynamic system is a hot topic. However, the current statistical model and inference approach is known as a large p small n problem. How to reduce the dimension of the dynamic model and improve the accuracy of estimation is more important. To address this question, the authors take some known parameters and structure of system as priori knowledge and incorporate it into dynamic model. At the same time, they decompose the whole dynamic model into subset network modules, based on different modules, and then they apply different estimation approaches. This technique is called Rao Blackwellised particle filters decomposition methods. To evaluate the performance of this method, the authors apply it to synthetic data generated from repressilator model and experimental data of the JAK-STAT pathway, but this method can be easily extended to large-scale cases. PMID- 26816395 TI - Kinetic model of metabolic network for xiamenmycin biosynthetic optimisation. AB - Xiamenmycins, a series of prenylated benzopyran compounds with anti-fibrotic bioactivities, were isolated from a mangrove-derived Streptomyces xiamenensis. To fulfil the requirements of pharmaceutical investigations, a high production of xiamenmycin is needed. In this study, the authors present a kinetic metabolic model to evaluate fluxes in an engineered Streptomyces lividans with xiamenmycin oriented genetic modification based on generic enzymatic rate equations and stability constraints. Lyapunov function was used for a viability optimisation. From their kinetic model, the flux distributions for the engineered S. lividans fed on glucose and glycerol as carbon sources were calculated. They found that if the bacterium can utilise glucose simultaneously with glycerol, xiamenmycin production can be enhanced by 40% theoretically, while maintaining the same growth rate. Glycerol may increase the flux for phosphoenolpyruvate synthesis without interfering citric acid cycle. They therefore believe this study demonstrates a possible new direction for bioengineering of S. lividans. PMID- 26816396 TI - Knowledge-based three-body potential for transcription factor binding site prediction. AB - A structure-based statistical potential is developed for transcription factor binding site (TFBS) prediction. Besides the direct contact between amino acids from TFs and DNA bases, the authors also considered the influence of the neighbouring base. This three-body potential showed better discriminate powers than the two-body potential. They validate the performance of the potential in TFBS identification, binding energy prediction and binding mutation prediction. PMID- 26816397 TI - Extended particle swarm optimisation method for folding protein on triangular lattice. AB - In this study, the authors studied the protein structure prediction problem by the two-dimensional hydrophobic-polar model on triangular lattice. Particularly the non-compact conformation was modelled to fold the amino acid sequence into a relatively larger triangular lattice, which is more biologically realistic and significant than the compact conformation. Then protein structure prediction problem was abstracted to match amino acids to lattice points. Mathematically, the problem was formulated as an integer programming and they transformed the biological problem into an optimisation problem. To solve this problem, classical particle swarm optimisation algorithm was extended by the single point adjustment strategy. Compared with square lattice, conformations on triangular lattice are more flexible in several benchmark examples. They further compared the authors' algorithm with hybrid of hill climbing and genetic algorithm. The results showed that their method was more effective in finding solution with lower energy and less running time. PMID- 26816398 TI - Sparse electrocardiogram signals recovery based on solving a row echelon-like form of system. AB - The study of biology and medicine in a noise environment is an evolving direction in biological data analysis. Among these studies, analysis of electrocardiogram (ECG) signals in a noise environment is a challenging direction in personalized medicine. Due to its periodic characteristic, ECG signal can be roughly regarded as sparse biomedical signals. This study proposes a two-stage recovery algorithm for sparse biomedical signals in time domain. In the first stage, the concentration subspaces are found in advance. Then by exploiting these subspaces, the mixing matrix is estimated accurately. In the second stage, based on the number of active sources at each time point, the time points are divided into different layers. Next, by constructing some transformation matrices, these time points form a row echelon-like system. After that, the sources at each layer can be solved out explicitly by corresponding matrix operations. It is noting that all these operations are conducted under a weak sparse condition that the number of active sources is less than the number of observations. Experimental results show that the proposed method has a better performance for sparse ECG signal recovery problem. PMID- 26816399 TI - Transcriptome marker diagnostics using big data. AB - The big omics data are challenging translational bioinformatics in an unprecedented way for its complexities and volumes. How to employ big omics data to achieve a rivalling-clinical, reproducible disease diagnosis from a systems approach is an urgent problem to be solved in translational bioinformatics and machine learning. In this study, the authors propose a novel transcriptome marker diagnosis to tackle this problem using big RNA-seq data by viewing whole transcriptome as a profile marker systematically. The systems diagnosis not only avoids the reproducibility issue of the existing gene-/network-marker-based diagnostic methods, but also achieves rivalling-clinical diagnostic results by extracting true signals from big RNA-seq data. Their method demonstrates a better fit for personalised diagnostics by attaining exceptional diagnostic performance via using systems information than its competitive methods and prepares itself as a good candidate for clinical usage. To the best of their knowledge, it is the first study on this topic and will inspire the more investigations in big omics data diagnostics. PMID- 26816400 TI - Patient identification and tube labelling - a call for harmonisation. AB - Venous blood sampling (phlebotomy) is the most common invasive procedure performed in patient care. Guidelines on the correct practice of phlebotomy are available, including the H3-A6 guideline issued by the Clinical Laboratory Standards Institute (CLSI). As the quality of practices and procedures related to venous blood sample collection in European countries was unknown, the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase conducted an observational study in 12 European countries. The study demonstrated that the level of compliance of phlebotomy procedures with the CLSI H3-A6 guideline was unacceptably low, and that patient identification and tube labelling are amongst the most critical steps in need of immediate attention and improvement. The process of patient identification and tube labelling is an essential safety barrier to prevent patient identity mix-up. Therefore, the EFLM Working Group aims to encourage and support worldwide harmonisation of patient identification and tube labelling procedures in order to reduce the risk of preanalytical errors and improve patient safety. With this Position paper we wish to raise awareness and provide recommendations for proper patient and sample identification procedures. PMID- 26816401 TI - Acceptance of Illness after Surgery in Patients with Breast Cancer in the Early Postoperative Period. AB - The breast cancer is the most common cancer in women, both in Poland and in the world. Consequences entail a disruption in the physical, psychological and social functioning. The aim of the study was to assess the acceptance of illness by patients treated for breast cancer in the early postoperative period. MATERIAL AND METHODS: The research was conducted on the group of 100 consecutive patients aged 32-80 years (median 56 years) who underwent surgery for breast cancer in the Centre of Oncology in Bydgoszcz w 2014 roku. 68 of women had mastectomy, 32 of women had conservative surgery. Polling was conducted in the early period after surgery. The original questionnaire containing closed questions the scale of acceptance of the disease (AIS) as well as mental adaptation to cancer (Mini-Mac) was used in the study. RESULTS: 38% of patients had high acceptance of the disease, 48% average and 14% had low acceptance. Patients after conservative surgery had a higher average values for the mental strategies to cope with the disease, for the fighting spirit (23.1), helplessness and hopelessness (13.5), positive revaluation (23), the patients had a lower average (16.5) in the strategy to absorb anxiety. Patients after conservative surgery had a higher average for constructive style (2.6) but lower for destructive style (1.5). High level of mental coping with the disease was observed in 53%of patients with constructive style and 4% of patients with destructive style. While, a low level of mental coping with the dosease was observed in 5% of patients with constructive style and 46% of patients with destructive style. CONCLUSIONS: Almost half of women after mastectomy or conservative surgery had an average acceptance of the disease. The disease was accepted best by educated women living in the cities, white-collar workers with a good economic situation. The following factors were affected the better management of the disease, in order: age, education, current occupation and economic situation, while the type of surgery did not affect better management. More than half of women, regardless of the type of surgery reflected the high level of constructive style. PMID- 26816402 TI - Comparison of Lymphatic System Staging Classifications in Patients with Gastric Cancer. AB - Despite an observed decrease in the incidence of gastric cancer, it still remains an important clinical problem. It is the fourth most common cancer in the world and the second cause of death in cancer patients. The quality of lymphadenectomy procedure and the number of analysed lymph nodes are both important factors influencing the treatment of the patient. The aim of the study was to compare the lymph node ratio staging system with the 6th and 7th edition of the TNM classification. MATERIAL AND METHODS: A group consisting of 493 patients who underwent surgery in 1998-2010 due to gastric cancer was used to compare the staging systems. Following statistical analysis, the following cut-off points were adopted for the lymph node ratio for the purpose of comparison: 0, from 0.05 to 0.3, from 0.3 to 0.5 and over 0.5. Subsequently the homogeneity (using chi square test for linear trend) and the predictive value of the different classifications (using Akaike information criterion) were assessed in order to compare the lymph node ratio staging system with the 6th and 7th edition of the TNM classification. RESULTS: The lymph node ratio classification has a higher discriminatory value than the TNM classifications (higher linear trend result). What is more, the lymph node ratio classification (LNR) had a lower Akaike information criterion value, which means that it has a higher prognostic value than the other classifications. ROC curves and the area under the curve (AUC) were utilised for the analysis of predictive value of the different classifications in patients with gastric cancer. CONCLUSION: One may conclude, therefore, that the lymph node ratio staging system is the best classification of the lymphatic system in the presented group of patients. PMID- 26816403 TI - Evaluation of Patient Feedback following Laparoscopic Cholecystectomy based on Information Described in the Informed Consent form Developed by the Association of Polish Surgeons. AB - The cholecystectomy procedure is the most routinely performed intervention in general surgery. The current international gold standard is via the laparoscopic approach. It is a safe, minimally-invasive procedure; however, it is associated with complications in 1% of cases. The aim of the study was to analyze patient feedback, by means of a survey, to determine how much knowledge patients possessed about their disease state and proposed surgical intervention, based primarily on information contained within the informed consent form developed by the Association of Polish Surgeons. MATERIAL AND METHODS: This study involved the participation of 51 patients who underwent laparoscopic cholecystectomy, indicated by a diagnosis of gallstones, in the years 2014 and 2015. RESULTS: Despite having signed the informed consent form, there was considerable variation among the responses given to the survey by the 51 patients in this study. Some patients' responses were tangential to the questions asked; many patients did not respond to any of the sub points. CONCLUSIONS: Given that this study is based on a small sample size of patients, it must be presumed that the process by which the patient declares his or her informed consent requires further consideration with respect to the means by which it is obtained. The authors of this study thus recommend that multimedia resources be harnessed as part of the process of obtaining the informed consent of patients prior to surgical intervention. PMID- 26816404 TI - The Use of the Enhanced Recovery After Surgery (ERAS) Protocol in Patients Undergoing Laparoscopic Surgery for Colorectal Cancer--A Comparative Analysis of Patients Aged above 80 and below 55. AB - Age is one of the principal risk factors for colorectal adenocarcinoma. To date, older patients were believed to achieve worse treatment results in comparison with younger patients due to reduced vital capacity. However, papers have emerged in recent years which confirm that the combination of laparoscopy and postoperative care based on the ERAS protocol improves treatment results and may be particularly beneficial also for elderly patients. The aim of the study was to compare the outcomes of laparoscopic surgery for colorectal cancer in combination with the ERAS protocol in patients aged above 80 and below 55. MATERIAL AND METHODS: The analysis included patients aged above 80 and below 55 undergoing elective laparoscopic colorectal resection for cancer at the 2nd Department of General Surgery of the Jagiellonian University. They were divided into two groups according to their age: >= 80 years of age (group1) and <= 55 years of age (group 2). Both groups were compared with regard to the outcome of surgery: length hospital stay, complications, hospital readmissions, degree of compliance with the ERAS protocol, and recovery parameters (tolerance of oral nutrition, mobilisation, need for opioids, restored gastrointestinal function). RESULTS: Group 1 comprised 34 patients and group 2, 43 patients. No differences were found between both groups in terms of gender, BMI, tumour progression or surgical parameters. Older patients typically had higher ASA scores. No statistically significant differences were found with regard to the length hospital stay following surgery (5.4 vs 7 days, p=0.446481), the occurrence of complications (23.5% vs 37.2%, p=0.14579) or hospital readmissions (2.9% vs 2.4%). The degree of compliance with the ERAS protocol in group 1 and 2 was 85.2% and 83.0%, respectively (p=0.482558). Additionally, recovery parameters such as tolerance of oral nutrition (82.4% vs 72.1%, p=0.28628) and mobilisation (94.1% vs 83.7%, p=0.14510) within 24 hours of surgery did not differ among the groups. However, a smaller proportion of older patients required opioids in comparison with younger patients (26.5% vs 55.8%, p=0.00891). CONCLUSIONS: Similar levels of compliance with the ERAS protocol may be achieved among patients aged >= 80 and younger patients. When laparoscopy is combined with the ERAS protocol, age does not seem to be a significant factor that could account for worse outcomes. Therefore, older patients should not be excluded from perioperative care based on ERAS principles. PMID- 26816405 TI - Quality of Life Aspects Determining The-Bio-Psycho-Social Functioning of Patients in The-Perspective of a Planned Extensive Sphincter's Repair Procedure. AB - Damage to the sphincter, regardless of its pathogenesis, consists in the impossibility to control the physiology, or the so-called faecal incontinence. This implies changes in the whole bio-psycho-social functioning of the patients, and thus affects the satisfaction with their quality of life, conditioned by their health status. The problem affects around 5 to 7% of the population. Often enough, the only hope for those patients are repair procedures of the sphincter mechanism. The aim of the study was to evaluate key aspects of quality of life which determine the psycho-social status of patients with endogenous or iatrogenic sphincter damage in the perspective of a planned extensive sphincter's repair procedure. MATERIAL AND METHODS: The study group consisted of 52 people, 26 women and 26 men, aged 19-72. The scale by Rockwood--Fecal Incontinency Quality of Life--was used as the basic research tool which evaluates the quality of life in four aspects: 1/behavioral (Lifestyle) 2/cognitive (Coping) 3/emotional (Depression) 4/overall self-assessment (Embarrasment). The degree of incontinence was determined based on point scales of Jorge Wexner (JW scale) and the Fecal Incontinenece Severity Index (FISI scale). Structured diagnostic interview was also used in the study. RESULTS: The results show that lack of control over the basic physiological functions disintegrates the quality of life in all evaluated aspects related to somatic, psychological and social functioning. FIQL: Lifestyle (LS) - 1.96 pts Coping (C) - 1.67 pts Depression (D) - 2.1 pts Embarrasment (E) - 1.79 pts Conclusions. The FIQL results presented explain the fact that among 52 patients followed, 50 decided to conduct extensive reconstructive procedures, although the results are not statistically optimistic and the risk of complications is relatively high. PMID- 26816406 TI - Damage of Central Catheters in Home Parenteral Nutrition Patients. AB - According to the ESPEN and ASPEN guidelines, in the case of a long-term (>3 month) parenteral nutrition should be administered via a subcutaneous central venous catheter (CVC). There are three types of mechanical complications of tunnelled central catheter: catheter rupture, occlusion by TPN depositing and thrombofibrotic occlusion. The aim of the study was to analyse the incidence of complications central catheter in a group of patients receiving HPN. MATERIAL AND METHODS: Between January 2010 and June 2014, HPN was conducted in 584 patients (306 women and 278 men), ninety-nine patients were enrolled in the study: 67 women and 32 men in whom mechanical complications of central catheters were found. RESULTS: Among 99 patients, 71 used the tunnelled Broviac catheter. Groshong catheters were placed only in patients receiving parenteral nutrition due to cancer. Analyses have shown differences between the older and younger in the number of mechanical complications. Younger patients were found to have a larger number of catheter complications (1.6 +/- 1.1) in comparison with older patients (1.3 +/- 0.7). The catheter that was most commonly damaged was the Broviac catheter 76.8%. The most frequent type of mechanical complications was catheter rupture 64.81%. CONCLUSIONS: Mechanical complications of tunnelled central catheters in HPN patients can be repaired in an outpatient setting in half of the cases, which enables continuation of parenteral nutrition without the need to hospitalise the patient. The centres that conduct HPN should offer 24 hour care and help in case of problems with the central venous line to the patients. PMID- 26816407 TI - Surgical Trap of a Routine Procedure. Scrotal Hernia with Concomitant Sliding of the Urinary Bladder--Case Report. AB - The content of the hernial sac may comprise peritoneal cavity elements, such as small and large bowel loops, visceral adipose tissue, the greater omentum, appendix (amyand hernia), and Meckel's diverticulum. The sliding of part of the urinary bladder wall to the inguinal canal is rare, being observed in 1%-4% (0.5% 3%) of inguinal hernia cases. Complete migration of the urinary bladder to the scrotum is considered a rare anomaly. As of today, 100 such cases have been described. PMID- 26816408 TI - Abdominal Cavity Eventration Treated by Means of the "Open Abdomen" Technique Using the Negative Pressure Therapy System--Case Report and Literature Review. AB - Wound dehiscence is a surgical complication in which the wound ruptures along the surgical suture with abdominal cavity bowel displacement. It is observed in 0.2 6% of operated patients. The extensive wound is a gateway for infection. Moreover, increased secretion of serous fluid induces a hygienic problem and may lead to secondary skin infections or bedsores. The negative pressure wound therapy (NPWT) system is an innovative therapeutic method. It perfectly executes the TIME strategy, receiving more and more recognition. The study presented a case of a 62-year old male patient after several consecutive wound dehiscence episodes who was primarily treated for rectal cancer by means of low anterior resection of the rectum. Due to acute respiratory insufficiency after several operations, wound necrosis with dehiscence was observed. Considering the high risk of perioperative death we abandoned surgical treatment and introduced conservative management using negative pressure wound therapy until the patient's health improved. Literature regarding the above-mentioned issue was also reviewed. PMID- 26816409 TI - Epidemiology and Results of Treatment of Colorectal Cancer in Poland. PMID- 26816410 TI - Single Incision Laparoscopic Cholecystectomy--Making it Cost-Effective. PMID- 26816411 TI - JCCA Special Issue December 2015-Sports Chiropractic. PMID- 26816412 TI - Self-reported attitudes, skills and use of evidence-based practice among Canadian doctors of chiropractic: a national survey. AB - OBJECTIVES: To identify Canadian chiropractors' attitudes, skills and use of evidence based practice (EBP), as well as their level of awareness of previously published chiropractic clinical practice guidelines (CPGs). METHODS: 7,200 members of the Canadian Chiropractic Association were invited by e-mail to complete an online version of the Evidence Based practice Attitude & utilisation SurvEy (EBASE); a valid and reliable measure of participant attitudes, skills and use of EBP. RESULTS: Questionnaires were completed by 554 respondents. Most respondents (>75%) held positive attitudes toward EBP. Over half indicated a high level of self-reported skills in EBP, and over 90% expressed an interest in improving these skills. A majority of respondents (65%) reported over half of their practice was based on evidence from clinical research, and only half (52%) agreed that chiropractic CPGs significantly impacted on their practice. CONCLUSIONS: While most Canadian chiropractors held positive attitudes towards EBP, believed EBP was useful, and were interested in improving their skills in EBP, many did not use research evidence or CPGs to guide clinical decision making. Our findings should be interpreted cautiously due to the low response rate. PMID- 26816414 TI - A posterior ring apophyseal fracture and disc herniation in a 21-year-old competitive basketball player: a case report. AB - OBJECTIVE: To describe the diagnosis and management of a competitive male basketball player with discogenic low back pain and presence of an old posterior ring apophyseal fracture (PRAF). This case will highlight the importance of early recognition and considerations regarding patient management for this differential of radiating low back pain. CLINICAL FEATURES: A 21-year-old provincial basketball player presented with recurrent radiating low back pain into the left groin and lower limb. After several weeks of persistent symptoms including pain, muscle weakness, and changes in the Achilles deep tendon reflex, imaging was obtained that revealed a large disc extrusion with an old posterior ring apophyseal fracture. In collaboration with a spine surgeon and family physician, the patient was treated using a conservative, multimodal approach. Treatment consisted of graded mobilizations, spinal manipulative therapy, interferential current, and soft tissue therapy to the lumbar spine. Rehabilitation exercises focused on centralizing symptoms and improving strength, proprioception and function of the lower limb. After a period of 8 weeks, the patient was able to complete all activities of daily living without pain in addition to returning to basketball practice. SUMMARY: PRAF is a unique condition in the immature spine and recent evidence suggests that those involved in sports requiring repetitive motion of the lumbar spine may be at increased risk. The astute clinician must consider this differential in young populations presenting with discogenic low back pain, as a timely diagnosis and necessary referral may allow for effective conservative management to reduce symptoms. Equally as important, one must be aware of the complications from PRAF as a contributing source of low back pain and dysfunction into adulthood. Knowing when to refer for advanced imaging and/or a surgical consult given the variable clinical presentation and prognosis is an essential component to care. PMID- 26816413 TI - The effectiveness of structured patient education for the management of musculoskeletal disorders and injuries of the extremities: a systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration. AB - PURPOSE: To determine the effectiveness of structured patient education for the management of musculoskeletal disorders and injuries of the extremities. METHODS: We searched MEDLINE, EMBASE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials from January 1, 1990 to March 14, 2015. Paired reviewers independently screened titles and abstracts for eligibility. The internal validity of studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Results from studies with a low risk of bias were synthesized using the best-evidence synthesis methodology. RESULTS: We identified two randomized trials with a low risk of bias. Our review suggests that: 1) multimodal care and corticosteroid injections lead to faster pain relief and improvement than reassurance and advice in the short-term and similar outcomes in the long-term for patients with persistent lateral epicondylitis; and 2) providing health education material alone may be less effective than multimodal care for the management of persistent patellofemoral pain syndrome. CONCLUSION: Our systematic search of the literature demonstrates that little is known about the effectiveness of structured patient education for the management of musculoskeletal disorders and injuries of the extremities. Two studies suggest that when used alone, structured patient education may be less effective than other interventions used to manage persistent lateral epicondylitis and persistent patellofemoral syndrome. PMID- 26816415 TI - Multidisciplinary approach to non-surgical management of inguinal disruption in a professional hockey player treated with platelet-rich plasma, manual therapy and exercise: a case report. AB - OBJECTIVE: To present the clinical management of inguinal disruption in a professional hockey player and highlight the importance of a multidisciplinary approach to diagnosis and management. CLINICAL FEATURES: A professional hockey player with recurrent groin pain presented to the clinic after an acute exacerbation of pain while playing hockey. INTERVENTION: The patient received a clinical diagnosis of inguinal disruption. Imaging revealed a tear in the rectus abdominis. Management included two platelet-rich plasma (PRP) injections to the injured tissue, and subsequent manual therapy and exercise. The patient returned to his prior level of performance in 3.5 weeks. DISCUSSION: This case demonstrated the importance of a multidisciplinary team and the need for advanced imaging in athletes with groin pain. SUMMARY: Research quality concerning the non surgical management of inguinal disruption remains low. This case adds evidence that PRP, with the addition of manual therapy and exercise may serve as a relatively quick and effective non-surgical management strategy. PMID- 26816418 TI - Adolescent sex education in India: Current perspectives. PMID- 26816417 TI - Unexpected Salter-Harris type II fracture of the proximal phalanx of the second toe: a chiropractic perspective. AB - OBJECTIVES: To discuss the diagnosis and management of a Salter-Harris type II fracture in a nine-year-old girl who was managed conservatively. CLINICAL FEATURES: A nine-year-old girl fell while playing in bare feet in the grass. She experienced pain when she walked or moved her toe. There was minor swelling and bruising. INTERVENTION AND OUTCOME: Plain film radiographs revealed a Salter Harris type II fracture of the 2(nd) proximal phalanx. Her toe was stabilized and she was referred to an orthopedist. Orthopedic management involved a taping procedure. After three weeks, her fracture healed and she was pain free. SUMMARY: Chiropractors may consider radiography of post-traumatic injury sites even with equivocal examination findings despite histories suggesting seemingly innocuous mechanisms of injury. PMID- 26816416 TI - Conservative management of an elite ice hockey goaltender with femoroacetabular impingement (FAI): a case report. AB - OBJECTIVE: To detail the presentation of an elite male ice hockey goaltender with cam-type femoroacetabular impingement (FAI) and acetabular labral tears. This case will outline the prevalence, clinical presentation, imaging criteria, pathomechanics, and management of FAI, with specific emphasis on the ice hockey goaltender. CLINICAL FEATURES: A 22-year old retired ice hockey goaltender presented to a chiropractor after being diagnosed by an orthopaedic surgeon with MRI confirmed left longitudinal and chondral flap acetabular labral tears and cam type femoroacetabular impingement (FAI). As the patient was not a candidate for surgical intervention, a multimodal conservative treatment approach including manual therapy, electroacupuncture and rehabilitation exercises were implemented. SUMMARY: FAI is prevalent in ice hockey players, particularly with goaltenders. Both skating and position-dependent hip joint mechanics involved in ice hockey may exacerbate or contribute to acquired and congenital forms of symptomatic FAI. As such, practitioners managing this population must address sport-specific demands in manual therapy, rehabilitation and physical training, to improve functional outcomes and prevent future injury. PMID- 26816419 TI - Yoga and mental health services. PMID- 26816420 TI - Indian marriage laws and mental disorders: Is it necessary to amend the legal provisions? PMID- 26816421 TI - Is psychiatry intervention in Indian setting complete? PMID- 26816422 TI - Suicide in India - changing trends and challenges ahead. PMID- 26816423 TI - Efficacy of Yoga therapy for the management of psychopathology of patients having chronic schizophrenia. AB - BACKGROUND: There is a large body of literature and scientific data regarding the efficacy of pharmacological and psychosocial interventions for schizophrenia, however, studies on Yoga therapy is scanty. Yoga is a means of balancing and harmonizing the body, mind and emotion, and for enlightening the mind and upliftment of the total personality. AIMS: The present study was conducted to determine the efficacy of Yoga therapy as an adjunctive therapy and to see its effects on psychopathology on the patients suffering from chronic schizophrenia. SETTINGS AND DESIGN: Pre- and post-test design with the control group. MATERIALS AND METHODS: It is a study using purposive sampling technique by which 30 chronic schizophrenic patients were selected and 15 patients were randomly assigned to Yoga therapy along with pharmacotherapy (experimental group), and 15 were assigned pharmacotherapy alone (control group) after the baseline assessment using Positive and Negative Syndrome Scale (PANSS). The Yoga group attended Yoga therapy everyday for about 11/2 h including motivational and feedback session. RESULTS: At the end of 1 month postassessment was done, and schizophrenic patients, who received the yogic intervention showed better rating than those in pharmacotherapy alone on PANSS variables. CONCLUSION: Yoga could be a right choice for improving psychopathology resulting in better quality of life along with other pharmacological management and psychosocial interventions. PMID- 26816424 TI - Consultation-liaison psychiatry services: Difference in the patient profile while following different service models in the medical emergency. AB - AIM: To compare "consultation" and "hybrid" models of consultation-liaison (CL) services provided to patients visiting the medical emergency outpatient services. MATERIALS AND METHODS: Over the period of 18 months, two different models of consultation psychiatry services (July 2012 to March 2013-consultation model, April 2013 to December 2013 hybrid model) were compared. In the consultation model, the psychiatry resident was available on call to the internists. Whereas, for the hybrid model psychiatry resident was stationed in the medical emergency and was available to assess the patients directly requiring psychiatric evaluation. RESULTS: During the first 9 months, 22,000 patients were evaluated in various emergency medical outpatient services, of which 383 (1.74%) were referred to the on-call psychiatry CL team. However, when the hybrid model was followed, the number of patients evaluated by the psychiatry resident increased to 594 out of 24,737 patients (2.4%) who reported to the emergency during the next 9 months period. There was a substantial increase in the proportion of cases with medical illnesses for which psychiatric consultation was sought, and a change in psychiatric diagnostic profile was observed too. When compared to the consultation model, the hybrid model was associated with greater use of medications, investigations, referrals and psychological measures in the emergency setting itself. CONCLUSIONS: Following a hybrid model in the medical emergency leads to an increase in the number of total psychiatric consultations and more extensive management of patients. PMID- 26816425 TI - Comparative study on perceived abuse and social neglect among rural and urban geriatric population. AB - CONTEXT: Elder abuse and social neglect are unrecognized problem. Many forms of elder abuse exist including physical, psychological, financial, sexual and social neglect. Social neglect is experienced by elderly through loss of friends and family members. AIM: Comparison of perceived abuse and social neglect among elderly residing in selected rural and urban areas. SETTINGS AND DESIGN: Study setting was a rural area Pohir and urban area Jamalpur of district Ludhiana. SUBJECTS AND METHODS: A sample of 200 subjects (100 subjects each from rural and urban area respectively) of age 60 years and above was drawn by cluster sampling technique and interview method was used to collect data by using Likert scale. STATISTICAL ANALYSIS: Descriptive and inferential statistics were carried out with SPSS package. RESULTS: Results of the present study revealed that perceived physical abuse (25%) was higher among elderly residing in rural and it was found significantly higher among female elderly who were illiterate, widow/widower and partially dependent on caregiver whereas perceived psychological abuse (71%), financial abuse (37%) and social neglect (74%) were higher among elderly residing in urban. A significant association was found between psychological abuse and educational status, which inferred that as the level of education increases perception of psychological abuse also increases. The perceived financial abuse was significantly higher among male elderly who were financially independent. CONCLUSION: It was concluded that social neglect was most common, followed by psychological abuse and financial abuse among elderly residing in urban whereas physical abuse was more prevalent among elderly residing in rural. PMID- 26816426 TI - Mysore study: A study of suicide notes. AB - BACKGROUND: Suicide is one of the leading causes of preventable deaths. Recent data suggest South India as one of the regions with highest suicide rates in the world. In 2013, 134,799 people committed suicide in India according to the statistics released by the National Crime Records Bureau. Suicide note is one of the most important sources to understand suicide, which may be beneficial in suicide prevention. Studies on suicidal notes from this part of the world are sparse. OBJECTIVE: The aim was to study the themes in suicide notes that might be useful in prevention strategies. MATERIALS AND METHODS: A descriptive study of all suicide notes of those individuals who committed suicide between 2010 and 2013 available with Police Department, Mysore district was obtained and analyzed. RESULTS: A total of 22 suicide note were available. A majority of suicide note was in age group of 16-40 years (86%) and most were men (59%). All suicide notes were handwritten, the majority (70%) in regional language Kannada. Length of notes varied from just few words to few pages. Contents of suicide notes included apology/shame/guilt (80%), love for those left behind (55%) and instruction regarding practical affairs (23%). Most have blamed none for the act (50%). 23% mentioned that they are committing suicide to prove their innocence. 32% mentioned a last wish. CONCLUSION: The majority of suicidal note contained "guilt" which is a strong indicator of possible depression in deceased. Creating awareness about suicide among public and ensuring access to professionals trained in suicide prevention is need of the hour in this part of the world. PMID- 26816427 TI - Isolated sleep paralysis and hypnic hallucinations in schizophrenia. AB - BACKGROUND: Usually remembered in the context of Narcolepsy-Cataplexy syndrome, isolated sleep paralysis (SP) and hypnic hallucination are widely prevalent and because of the overlap of symptoms with schizophrenia, their identification is important but unrecognized. AIMS: To determine the presence of SP and hypnic hallucinations (HH) in people with schizophrenia and schizoaffective disorder. STUDY DESIGN: Cross-sectional survey. METHODS: Participants were patients receiving follow-up care for schizophrenia from Assertive Community Treatment Team. A screening questionnaire was administered during their routine follow-up visits. RESULTS: Of 71 respondents (49 males, 22 females) only 11 (10 males and 1 female), that is, 15% reported SP, and 12 (7 males and 5 females), that is, 16.9% reported HH, a considerably low prevalence. CONCLUSION: It is difficult to study the presence of SP and HH in patients with active or residual symptoms of schizophrenia, and more refined studies and appropriate questionnaires are required. The possibility of SP and HH confounding or being misdiagnosed as psychotic symptoms needs to be borne in mind. PMID- 26816429 TI - Suicide prevention competencies among urban Indian physicians: A needs assessment. AB - INTRODUCTION: India accounts for the highest estimated number of suicides in the World. In 2012, more than 258,000 of the 804,000 suicide deaths worldwide occurred in India. Early identification and effective management of suicidal ideation and behavior are paramount to saving lives. However, mental health resources are often scarce and limited. Throughout India, there is a severe shortage in mental health professions trained, which results in a treatment gap of about 90%. A comprehensive needs assessment was undertaken to identify the nature of the deficits in suicide prevention training for physicians in three Indian cities: Mumbai, Ahmedabad, and Mysore. MATERIALS AND METHODS: The study was carried out in several concurrent phases and used a mixed-method approach of converging quantitative and qualitative methodologies. Data were collected using survey questionnaires, focus groups, consultations, and environmental scans. A total of 46 physicians completed the questionnaire. Focus groups were conducted in Mumbai and Ahmedabad with 40 physicians. Consultations were carried out with psychiatrists and psychiatric residents from hospitals and clinics in Mumbai, Ahmedabad, and Mysore. RESULTS: Training gaps in suicide prevention exist across the health care professions. Existing training lacks in both quality and quantity and result in critical deficits in core competencies needed to detect and treat patients presenting with suicidal ideation and behavior. Only 43% of the surveyed physicians felt they were competent to treat suicidal patients. The majority of surveyed physicians believed they would greatly benefit from additional training to enhance their suicide risk assessment and intervention skills. CONCLUSIONS: There is a dire need for medical schools to incorporate suicide prevention training as a core component in their medical curricula and for continuing medical education training programs for physicians to enhance competencies in early detection and management of suicidal behavior. PMID- 26816428 TI - Comparative study of sexual dysfunction and serum prolactin level associated with olanzapine, risperidone, and clozapine in patients with remitted schizophrenia. AB - BACKGROUND: Sexual dysfunctions have been a major side effect of the second generation anti-psychotic drugs which often affects treatment compliance in patients with schizophrenia. There is no/few systematic review or research addressing sexual dysfunction and their effect on serum prolactin level among different atypical antipsychotics in India. AIMS: To determine and compare the frequency of sexual dysfunction associated with olanzapine, risperidone, and clozapine and their effect on serum prolactin level in remitted patients with schizophrenia. SETTINGS AND DESIGN: Cross-sectional hospital-based study. Recruitment by purposive sampling. Estimation of serum prolactin was done using enzyme-linked immunosorbent assay technique. MATERIALS AND METHODS: The total sample size was 103, consisting of 31, 23, and 19 patients in olanzapine, risperidone, and clozapine groups, respectively and 30 controls. A Brief Psychiatric Rating Scale, Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and Sexual Functioning Questionnaire were administered. Analysis of variance was used to compare clinical variables. Chi-square test was used to identify the frequency of sexual dysfunction. Kruskal-Wallis test was used to compare UKU side effect, sexual dysfunction, and blood parameters across the study groups. RESULTS AND CONCLUSION: Eighty-six percentage reported sexual dysfunction in one or more domains of sexual functioning in risperidone group as compared to 48.3% in olanzapine and 31% in clozapine groups, respectively. Prolactin level elevation was statistically significant in risperidone group followed by clozapine and olanzapine groups, respectively. PMID- 26816430 TI - Effectiveness of specific intervention on treatment adherence of persons with mental illness: A pilot study. AB - CONTEXT: Treatment nonadherence is one of the major obstacles in recovery even with the availability of a broad range of pharmacological and psychosocial treatments for persons with mental illnesses. AIMS: The aim was to evaluate the effectiveness of specific interventions in improvement of treatment adherence of persons with mental illnesses. SETTINGS AND DESIGN: A quasi-experimental study was conducted at a tertiary mental health care setting in North-east India. MATERIALS AND METHODS: Total 30 numbers of patients were selected randomly for the study. Treatment adherence was assessed using the Medication Adherence Rating Scale and a structured Treatment Adherence Checklist. Data were collected before and 1-month after the specific interventions to the patients and their family members. RESULTS: Result showed a significant improvement in the treatment adherence as verbalized by the patient (paired t = 3.973, P = 0.00, df = 29) as well as reported by the family members (paired t = 2.94, P = 0.00, df = 29) following the specific intervention. CONCLUSION: The study result suggested that specific intervention may be used for a better outcome of treatment for mental illnesses. The findings might be generalized following implementation of the intervention to a larger sample. PMID- 26816431 TI - People see what papers show! Psychiatry's stint with print media: A pilot study from Mumbai, India. AB - Mass media including television, internet, and newspapers influences public views about various issues by means of how it covers an issue. Newspapers have a wider reach and may affect the impact that a news story has on the reader by factors such as placement of the story within the different pages. We did a pilot study to see how two English newspapers from Mumbai, India were covering psychiatry related news stories. The study was done over a period of 3 months. We found a total of 870 psychiatry related news stories in the two newspapers over 3 months with the majority of them being covered in the main body of the newspapers. Sex related crime stories and/or sexual dysfunction stories received the highest coverage among all the news while treatment and/or recovery related stories received very little coverage. It is crucial that the print media takes more efforts in improving reporting of psychiatry-related stories and help in de stigmatizing psychiatry as a discipline. PMID- 26816432 TI - Changes in depression status in low socioeconomic perinatal subjects in rural India after supervised physical exercise: A randomized controlled study. AB - BACKGROUND: Perinatal depression is a major public health problem, affecting up to a quarter of all pregnant women in rural Asean countries and often leads to psychologic symptoms, lower quality of life, and higher health care costs. The purpose of this study was to assess the impact of supervised physical exercise on depression level of perinatal subjects. SUBJECTS/INTERVENTION: 60 subjects who fulfill the selection criteria were randomly assigned to exercise (Group-1, n=30) and control group (Group-2, n=30). Participants completed general screening form and Physical health questionnaire-9 (PHQ-9) before their intervention and again 4 weeks and 8 weeks later. Group-1 underwent aerobic training with 60-65% maximum heart rate and Group-2 was prescribed with handouts for 4 weeks. STATISTICS: Repeated-measures analysis of variance (ANOVA) was use to analyze group differences over time while controlling for baseline differences. RESULTS: Demographic and the baseline values show homogenous population (P>0.05). Patients in both groups experienced significant reduction in depression level. Group A showed reduction of 91.70% (P=0.00) as compared to Group B 69.01% (P=0.00). CONCLUSION: These results suggest that supervised physical exercise provides better improvement in depression status in perinatal subjects than providing handouts alone. PMID- 26816434 TI - The story of Satyanand. PMID- 26816433 TI - Theoretical and practical issues related to the management of severe and refractory psychotic illness complicated by pulmonary embolism. AB - Pulmonary embolism (PE) is a potentially fatal condition. We describe the educative case of a young adult male, with a longstanding history of schizophrenia, who was receiving anticoagulant treatment because of repeated episodes of PE in the past. He presented with severe exacerbation of psychosis and did not respond to oral and parenteral antipsychotic medication during inpatient treatment. He was taken up for electroconvulsive therapy (ECT) and received a single ECT uneventfully. The ECT course had to be interrupted because of the unexpected development of a 4-day febrile illness, after which he experienced sudden onset breathlessness, which was diagnosed as acute-on-chronic PE. After the crisis resolved with 4 days of intensive care, he was managed with clozapine. We discuss concerns associated with the psychiatric management of patients with PE; special issues include the use of restraints, parenteral antipsychotic medications, anticoagulants, and ECT. PMID- 26816435 TI - Patient experience and the psychiatric discourse: Attempting to bridge incommensurable worlds. AB - Divergent worldviews, incommensurable frameworks, contrasting models, distinct foci, dissimilar logic, different realities, disparate cultures, and complex patient-physician interaction impact the clinical process and problematize decision-making. Attempting to understand the disease-illness divide, engage patient perspectives, go beyond the traditional biomedical understanding of mental illness and negotiate a shared plan for treatment are serious challenges for psychiatry. The challenge for psychiatrists is to appreciate patient reality and negotiate a shared plan of treatment. PMID- 26816436 TI - Web-of-rebirths: the 'karma' principle of Indian philosophy. PMID- 26816437 TI - Clozapine induced eosinophilia: An often neglected important adverse effect. PMID- 26816438 TI - Participation in activities of daily living can reduce loneliness in older adults. PMID- 26816439 TI - Innovative ways and customizing psychiatry training for undergraduates. PMID- 26816440 TI - Clarification in the nosology of conduct disorder. PMID- 26816441 TI - Delving into the perpetual debate in psychiatry. PMID- 26816442 TI - Carbamazepine induced optic neuropathy in an adolescent boy with conduct disorder: A rare case report. PMID- 26816443 TI - Retraction: The mystery of reincarnation. AB - [This retracts the article on p. S171 in vol. 55, PMID: 23858250.]. PMID- 26816444 TI - Integrative weaning index: New kid on the block! PMID- 26816445 TI - Can integrative weaning index be a routine predictor for weaning success? AB - OBJECTIVE: To assess the effectiveness of integrative weaning index (IWI) as a predictor of weaning success. MATERIALS AND METHODS: This is a prospective randomized controlled observer-blinded study and carried out on 120 patients of both sexes; patients who received mechanical ventilation for more than 24 h and met defined criteria for a weaning trial, underwent a 2-h spontaneous breathing trial with either IWI plus routine criteria of weaning (Group I n = 60) or routine criteria of weaning alone (control group) (Group C n = 60), in Group C the IWI was measured retrospective as it is not used in weaning decision. Those tolerated the trial would be immediately extubated. The primary outcome measure was the ability to maintain spontaneous, unassisted breathing for more than 48 h after extubation. Secondary outcome measures were the duration of mechanical ventilation, length of Intensive Care Unit (ICU) stay, and length of hospital stay. RESULTS: The mean duration (hours) of mechanical ventilation and length of ICU stay (days) were significantly shorter in the Group I where the IWI was used (83.6 +/- 34.3 vs. 97.49 +/- 47.2 h, P = 0.002 and 5.5 +/- 1.6 vs. 7.12 +/- 2.3 days, P = 0.03, respectively). Weaning success rate was significantly higher in the Group I (53 vs. 34, P = 0.0001) while weaning failure rate was significantly lower in the Group I C (7 vs. 26, P = 0.0001). CONCLUSION: IWI is a strong predictor of both successful and failed weaning. PMID- 26816447 TI - Chicken pox outbreak in the Intensive Care Unit of a tertiary care hospital: Lessons learnt the hard way. AB - Varicella-zoster virus (VZV) causes 2 clinically and epidemiologically distinct forms of diseases. Chickenpox (varicella) is the disease that results from primary infection with the VZV. Herpes zoster (HZ) results from the reactivation of VZV latently infecting the dorsal root ganglia. We are reporting an outbreak of varicella infection among the health care workers (HCWs) in the Intensive Care Unit (ICU) of a tertiary care hospital. We found transmission of varicella among eight HCWs of pulmonary ICU. They had a history of contact with a patient having HZ infection. Investigation of the outbreak was conducted as per guidelines. Better dissemination of information on disease transmission, isolation of infected patients inside the hospital, and adequate protection (including vaccination) for susceptible employees are important to prevent such outbreaks. PMID- 26816446 TI - Agreement between inferior vena cava diameter measurements by subxiphoid versus transhepatic views. AB - CONTEXT: Correcting hypovolemia is extremely important. Central venous pressure measurement is often done to assess volume status. Measurement of inferior vena cava (IVC) is conventionally done in the subcostal view using ultrasonography. It may not be possible to obtain this view in all patients. AIMS: We therefore evaluated the limits of agreement between the IVC diameter measurement and variation in subcostal and that by the lateral transhepatic view. SETTINGS AND DESIGN: Prospective study in a tertiary care referral hospital intensive care unit. SUBJECTS AND METHODS: After Institutional Ethics Committee approval and informed consent, we obtained 175 paired measurements of the IVC diameter and variation in both the views in adult mechanically ventilated patients. The measurements were carried out by experienced researchers. We then obtained the limits of agreement for minimum, maximum diameter, percentage variation of IVC in relation to respiration. STATISTICAL ANALYSIS USED: Bland-Altman's limits of agreement to get precision and bias. RESULTS: The limits of agreement were wide for minimum and maximum IVC diameter with variation of as much as 4 mm in both directions. However, the limits of agreement were much narrower when the percentage variation in relation to respiration was plotted on the Bland-Altman plot. CONCLUSIONS: We conclude that when it is not possible to obtain the subcostal view, it is possible to use the lateral transhepatic view. However, using the percentage variation in IVC size is likely to be more reliable than the absolute diameter alone. It is possible to use both views interchangeably. PMID- 26816448 TI - Mortality profile across our Intensive Care Units: A 5-year database report from a Singapore restructured hospital. AB - Intensive care remains an area of high acuity and high mortality across the globe. With a rapidly aging population, the disease burden requiring intensive care is growing. The cost of critical care also is rising with new technology becoming available rapidly. We present the all-cause mortality results of 5 years database established in a restructured, large public hospital in Singapore, looking at all three types of Intensive Care Units present in our hospital. These include medical, surgical, and coronary care units. PMID- 26816449 TI - Takotsubo cardiomyopathy in a patient with pituitary adenoma and secondary adrenal insufficiency. AB - We describe a case of Takotsubo cardiomyopathy in a case of pituitary macroadenoma in acute adrenal crisis. A 48-year-old man presented with acute onset altered sensorium, vomiting, and gasping. On admission, he was unresponsive and hemodynamically unstable. He was intubated and ventilated and resuscitated with fluids and inotropes. The biochemical evaluation revealed hyponatremia, hyperkalemia, and hypocortisolism. Hyponatremia was corrected with 3% hypertonic saline. Contrast enhanced computed tomography (CT) scan of the brain revealed a sellar-suprasellar mass with hypothalamic extension with no evidence of pituitary apoplexy. A diagnosis of invasive pituitary adenoma with the Addisonian crisis was made and steroid replacement was initiated. Despite volume resuscitation, he had persistent refractory hypotension, recurrent ventricular tachycardia, and metabolic acidosis. Electrocardiogram (ECG) showed ST elevation and T-wave inversion in lateral leads; cardiac-enzymes were increased suggestive of acute coronary syndrome. Transthoracic echocardiography showed severe regional wall motion abnormalities (RWMAs) involving left anterior descending territory and low ejection fraction (EF). Coronary angiogram revealed normal coronaries, apical ballooning, and severe left ventricular dysfunction, consistent with a diagnosis of Takotsubo's cardiomyopathy. Patient was managed with angiotensin-converting enzyme inhibitors and B-blockers. He improved over few days and recovered completely. At discharge, ECG changes and RWMA resolved and EF normalized to 56%. In patients with Addisonian Crisis with persistent hypotension refractory to optimal resuscitation, possibility of Takotsubo's cardiomyopathy should be considered. Early recognition of association of Takotsubos cardiomyopathy in neurological conditions, prompt resuscitation, and supportive care are essential to ensure favorable outcomes in this potentially lethal condition. PMID- 26816450 TI - Successful management of aluminium phosphide poisoning using intravenous lipid emulsion: Report of two cases. AB - Aluminum phosphide (ALP) is a cheap, easily available agricultural pesticide which causes lethal poisoning by liberation of phosphine and inhibition of cytochrome c oxidase thereby leading to cellular hypoxia. Although there is no known specific antidote, clinical trials are still going on. We present here two cases of ALP poisoning who were successfully managed by treatment with lipid emulsion and intravenous magnesium sulfate. PMID- 26816451 TI - Invasive aspergillosis in near drowning nonneutropenic patient. AB - Invasive aspergillosis in immunosuppressed people has been well documented, but to diagnose and treat in an immunocompetent individual after near drowning, it requires early suspicion and proper empirical treatment. We report a case diagnosed to have invasive aspergillosis with systemic dissemination of the infection to the brain, gluteal muscles, and kidneys after a fall in a chemical tank of a paper manufacturing company. He was ventilated for acute respiratory distress syndrome and managed with antibiotics and vasopressors. Due to nonresolving pneumonia and positive serum galactomannan, trans-tracheal biopsy was performed which confirmed invasive aspergillosis and was treated with antifungals. With the availability of galactomannan assay and better radiological investigative modalities, occurrence of such invasive fungal infections in cases of drowning patients should be considered early in such patients and treated with appropriate antifungals. PMID- 26816452 TI - Malarial pancreatitis: Case report and systematic review of the literature. AB - Malaria can cause a wide spectrum of clinical manifestations ranging from uncomplicated febrile illness to multiorgan failure. Pancreatitis is a rare complication of malaria with only a few reported cases. Herein, we describe a case of acute pancreatitis with multiorgan failure due to Plasmodium falciparum managed successfully with antimalarials and conservative treatment. We also perform a systematic review of literature for reports of acute pancreatitis due to Plasmodium infection. PMID- 26816453 TI - Pregnancy with severe influenza A (H1N1) related acute respiratory distress syndrome: Report of three cases from a rural critical care unit in India. PMID- 26816454 TI - The role of noninvasive ventilation in mild to moderate acute respiratory distress syndrome. PMID- 26816455 TI - Objective measurement of shade color in age estimation. AB - INTRODUCTION: Age estimation is an important subspecialty of forensic medicine. Dental hard tissues are highly resistant to degradation and putrefaction. Enamel is translucent and varies in color from light yellow to grey white. The color of the teeth has been reported to be affected by chronological age. Enamel color may also depend on environmental factors viz. diet, occupational habits, vitamin deficiencies, fluoride level in drinking water etc., It has been found that color changes in dentin vary from white to yellow. Studies have been done to measure the dentin color for age estimation. AIM: To find a correlation between the enamel color and chronological age and secondly to estimate the age of an individual from enamel color. MATERIAL AND METHODS: A total of 300 patients visiting the outpatient department of oral medicine and radiology were selected. Out of those, 150 were men and 150 women. The patients were divided into V groups based on the age. A thorough case history was taken for all the patients. Maxillary Central and Lateral incisor was used for the estimation of shade. The enamel color was evaluated using a VITA classical shade guide. STATISTICAL ANALYSIS: Data were exported to an Excel spread sheet and statistical analysis was performed using the SPSS. Linear regression analysis was used to find correlations between age and enamel shade. RESULTS: In the group 1 and 2 i.e. from 15 to 36 years, the shades A 2 and B 2 (reddish hue) was found to be most common. While in the group 3 and 4, shades ranged from A 3 to B 3 (brownish to yellowish hue). In the patients above 59 years i.e. group 5 the enamel shade with greyish hue was found to be most common. CONCLUSION: Age determination using enamel color can be tried in forensic cases in the identification of individuals with no birth records. PMID- 26816456 TI - Comparison of the bite mark pattern and intercanine distance between humans and dogs. AB - BACKGROUND: Bite marks show uniqueness due to specific characteristics and arrangement of teeth, but when it comes to bite mark analysis, it is complicated by numerous factors such as animal bite, abuse etc., Humans and pet animals (dog) bite marks analysis is by far the most demanding and complicated part of forensic dentistry. AIM: To analyze and compare bite marks of humans and the pet animals (dog) using indirect method, so as to assess its usefulness and application in forensic odontology. MATERIALS AND METHODS: 40 samples including 20 humans (10 males and 10 females) and 20 dogs of different breed were included in the study. Bite registration of all the samples were obtained on modeling wax and intercanine distance were measured. Data were analyzed and results were tabulated. RESULTS: Arch size and intercanine distance showed variable differences among humans and on average dogs showed more intercanine distance and arch size. Among dog breeds larger dogs showed larger variables when compared to smaller dogs. CONCLUSION: Assessment of bite marks evidences made by animals needs further investigation so that it can be a tool to assist the justice system to answer crucial questions. PMID- 26816457 TI - Ethnic variation of selected dental traits in Coorg. AB - PURPOSE: In a country like India, in addition to the great innate diversity, there are distinct migrant populations with unique dental traits. AIM: To assess the distribution and degree of expression of cusp of Carabelli of maxillary first permanent molars and shoveling trait of maxillary central incisors, between three ethnic groups of Coorg, namely Kodavas, Tibetans, and Malayalees. MATERIALS AND METHODS: A cross-sectional, indirect, anthropometric, study was carried out among 15- to 30-year-old subjects belonging to three different ethnic origins. A random sample consisting of 91 subjects were recruited for the study. The shovel trait of incisors and the Carabelli trait of molars were recorded according to the classification given by Hrdlicka and Sousa et al., respectively. STATISTICAL ANALYSIS: The Kruskal-Wallis test was employed to determine the difference in three populations for shoveling and Carabelli traits. Mann-Whitney Test was used for pair-wise comparisons of three populations. RESULT: Of the total 91 subjects, 31 were Kodavas, 30 Malayalees and 30 Tibetans. There was a statistically significant difference in shoveling trait among the three ethnic groups. For Carabelli traits, there was no statistically significant difference among three ethnic groups. CONCLUSION: The present study findings showed that Tibetans have a higher degree of shoveling trait than the selected South Indian ethnic groups. PMID- 26816458 TI - Envelopment technique and topographic overlays in bite mark analysis. AB - AIMS AND OBJECTIVES: The aims and objectives of our study were to compare four sequential overlays generated using the envelopment technique and to evaluate inter- and intraoperator reliability of the overlays obtained by the envelopment technique. MATERIALS AND METHODS: Dental stone models were prepared from impressions made from healthy individuals; photographs were taken and computer assisted overlays were generated. The models were then enveloped in a different color dental stone. After this, four sequential cuts were made at a thickness of 1mm each. Each sectional cut was photographed and overlays were generated. Thus, 125 overlays were generated and compared. RESULTS: The scoring was done based on matching accuracy and the data were analyzed. The Kruskal-Wallis one-way analysis of variance (ANOVA) test was used to compare four sequential overlays and Spearman's rank correlation tests were used to evaluate the inter- and intraoperator reliability of the overlays obtained by the envelopment technique. CONCLUSION: Through our study, we conclude that the third and fourth cuts were the best among the four cuts and inter- and intraoperator reliability were found to be statistically significant at 5% level that is 95% confidence interval (P < 0.05). PMID- 26816459 TI - Assessment of cheiloscopy in sex determination using lysochrome - A preliminary study. AB - INTRODUCTION: The present study was undertaken with the objective of ascertaining whether latent lip prints generated by persistent lipsticks and developed using lysochrome dyes have the potential of use in sex determination and personal identification. MATERIALS AND METHODS: This study included a total of 100 subjects (50 males and 50 females) whose latent lip prints were obtained by applying the persistent lipstick Revlon ColorStay Overtime((r)) manufactured by Revlon((r)) consumer products corporation, NewYork, USA, and lifting the prints with cellophane sheets. The prints were then developed using lysochrome dyes, and all the samples were blinded and then graded based on defined patterns from the Suzuki and Tsuchihashi classification. RESULTS: No two lip prints were found to be alike. Type I was found to be the most prevalent type. In the female population, Type I (61%) was most prevalent, followed by Type I' (28%), Type II (9%), Type III (2%), Type IV (1%), and Type V (1%); in the male population, Type I (33%) was most prevalent, followed by Type II (23%), Type III (18%), Type IV (14%), Type I' (10%), and Type V (3%). Two examiners were able to determine the correct sexes from the given sample sizes. Their interobserver agreement was assessed using the kappa coefficient for males (kappa =0.870) and females (kappa = 0.870). Their accuracy was assessed with a confidence interval (CI) of 91.48 99.38. CONCLUSION: Lysochrome dyes are very efficacious in developing latent lip prints. This preliminary study has conclusively proved that latent lip prints developed with lysochrome dyes hold the potential for use in sex determination and can be maintained in a digital database. PMID- 26816460 TI - Geriatric forensics - Part 2 "Prevalence of elder abuse and their potential forensic markers among medical and dental patients". AB - CONTEXT: This study is a continuation of the earlier studies and has been extended to investigate the potential forensic markers of elder abuse. AIMS: To determine the prevalence of elder abuse in various outpatient departments (OPDs). To study the associated parameters related to the abuser and the abused. To determine the existence of potential forensic markers of elder abuse. SETTINGS AND DESIGN: The subjects were randomly selected from the medical and the dental OPDs of the university. MATERIALS AND METHODS: Eight hundred and thirty two elderly subjects in the age range 40-60 years were interviewed using a questionnaire to determine the existence of elder abuse. The subjects were investigated and examined for weight, nutrition and hydration, vital signs, habits, existing visual and auditory capabilities, medications, disclosure of wills/deeds, signs of depression, and documented cleanliness. The mini-mental state examination, the Geriatric Depression Scale, the Clock drawing test, and the Brief Psychiatric Rating Scale were used to determine the potential forensic markers. STATISTICAL ANALYSIS USED: Mean values in percentage were determined by dividing the number of determined subjects by the total number of subjects for that parameter. RESULTS: About 37% in medical and 41% in dental OPDs were found to have suffered from abuse, mostly in the age group 60-70 years. Females received more abuse and a combination of son and daughter-in-law constituted most abusers. Various potential markers of elder abuse and neglect investigated among the elder abuse victims included depression (89%), signs of improper feeding (83%), changes in personal hygiene (69%), need for medical/dental treatment (78%), medication misuse (67%), changes in wills/deeds (26%), decubiti (10%), bruises (17%), skin tears (27%), and confusion (23%). CONCLUSIONS: Elder abuse exists in one or more forms in both medical and dental OPDs among both males and females in all age groups. PMID- 26816461 TI - Morphometric analysis of pulp size in maxillary permanent central incisors correlated with age: An indirect digital study. AB - CONTEXT: Teeth are hardest part of the body and are least affected by the taphonomic process. They are considered as one of the reliable methods of identification of a person in forensic sciences. AIM: The aim of the following study is to establish morphometeric measurements by AutoCad 2009 (Autodesk, Inc) of permanent maxillary central incisors in different age groups of Udaipur population. SETTING AND DESIGN: Hospital-based descriptive cross-sectional study carried out in Udaipur. MATERIALS AND METHODS: A study was carried out on 308 subjects of both genders with the age range of 9-68 years. Standardized intra oral radiographs were made by paralleling technique and processed. The radiographs were scanned and the obtained images were standardized to the actual size of radiographic film. This was followed by measuring them using software AutoCad 2009. STATISTICAL ANALYSIS USED: F-test, post-hoc test, Pearson's correlation test. RESULTS: For left maxillary central incisor, the total pulp area was found to be of 38.41 +/- 12.88 mm and 14.32 +/- 7.04 mm respectively. For right maxillary central incisor, the total pulp size was 38.39 +/- 14.95 mm and 12.35 +/- 5 mm respectively. Males (32.50, 32.87 mm(2)) had more pulp area when compared with females (28.82, 30.05 mm(2)). CONCLUSION: There was a decrease in total pulp area with increasing age which may be attributed to secondary dentin formation. PMID- 26816462 TI - Estimation of age based on tooth cementum annulations: A comparative study using light, polarized, and phase contrast microscopy. AB - CONTEXT: The identification of living or deceased persons using unique traits and characteristics of the teeth and jaws is a cornerstone of forensic science. Teeth have been used to estimate age both in the young and old, as well as in the living and dead. Gradual structural changes in teeth throughout life are the basis for age estimation. Tooth cementum annulation (TCA) is a microscopic method for the determination of an individual's age based on the analysis of incremental lines of cementum. AIM: To compare ages estimated using incremental lines of cementum as visualized by bright field microscopy, polarized microscopy, and phase contrast microscopy with the actual age of subject and to determine accuracy and feasibility of the method used. MATERIALS AND METHODS: Cementum annulations of 60 permanent teeth were analyzed after longitudinal ground sections were made in the mesiodistal plane. The incremental lines were counted manually using a light, polarized and phase contrast microscopy. Ages were estimated and then compared with the actual age of individual. STATISTICAL ANALYSIS: Analysis of variance (ANOVA), Student's t-test, the Pearson product moment corre (PPMCC) and regression analysis were performed. RESULTS: PPMCC value r = 0.347, 0.542 and 0.989 were obtained using light, polarized and phase contrast microscopy methods respectively. CONCLUSION: It was concluded that incremental lines of cementum were most clearly visible under a phase contrast microscope, followed by a polarized microscope, and then a light microscope when used for age estimation. PMID- 26816463 TI - Accuracy of bite mark analysis from food substances: A comparative study. AB - AIMS AND OBJECTIVES: The aims and objectives of the study were to compare the accuracy of bite mark analysis from three different food substances-apple, cheese and chocolate using two techniques-the manual docking procedure and computer assisted overlay generation technique and to compare the accuracy of the two techniques for bite mark analysis on food substances. MATERIALS AND METHODS: The individuals who participated in the study were made to bite on three food substances-apple, cheese, and chocolate. Dentate individuals were included in the study. Edentulous individuals and individuals having a missing anterior tooth were excluded from the study. The dental casts of the individual were applied to the positive cast of the bitten food substance to determine docking or matching. Then, computer generated overlays were compared with bite mark pattern on the foodstuff. RESULTS: The results were tabulated and the comparison of bite mark analysis on the three different food substances was analyzed by Kruskall-Wallis ANOVA test and the comparison of the two techniques was analyzed by Spearman's Rho correlation coefficient. CONCLUSION: On comparing the bite marks analysis from the three food substances-apple, cheese and chocolate, the accuracy was found to be greater for chocolate and cheese than apple. PMID- 26816464 TI - Dental age estimation of growing children by measurement of open apices: A Malaysian formula. AB - BACKGROUND: Age estimation is of prime importance in forensic science and clinical dentistry. Age estimation based on teeth development is one reliable approach. Many radiographic methods are proposed on the Western population for estimating dental age, and a similar assessment was found to be inadequate in Malaysian population. Hence, this study aims at formulating a regression model for dental age estimation in Malaysian children population using Cameriere's method. MATERIALS AND METHODS: Orthopantomographs of 421 Malaysian children aged between 5 and 16 years involving all the three ethnic origins were digitalized and analyzed using Cameriere's method of age estimation. The subjects' age was modeled as a function of the morphological variables, gender (g), ethnicity, sum of normalized open apices (s), number of tooth with completed root formation (N0) and the first-order interaction between s and N0. RESULTS: The variables that contributed significantly to the fit were included in the regression model, yielding the following formula: Age = 11.368-0.345g + 0.553No -1.096s - 0.380s.No, where g is a variable, 1 for males and 2 for females. The equation explained 87.1% of total deviance. CONCLUSION: The results obtained insist on reframing the original Cameriere's formula to suit the population of the nation specifically. Further studies are to be conducted to evaluate the applicability of this formula on a larger sample size. PMID- 26816465 TI - Evaluation of palatal rugae pattern in establishing identification and sex determination in Nalgonda children. AB - BACKGROUND: Establishing individual identification of a decedent only by dental means is a mammoth task in forensic odontology. Palatal rugae's uniqueness, its resistance to heat, and stability throughout life have been proved by its use as an alternative aid in individual identification where comparison of fingerprints and other records is difficult. AIMS AND OBJECTIVES: The aim of the present study was to analyze the role of palatal rugoscopy in personal identification and sex determination of Nalgonda pediatric population. MATERIALS AND METHODS: The study group consisted of 100 children having mixed dentition within the age range of 8 11 years, residing in Nalgonda district. Palatal rugae pattern, shape of the incisive papillae, length of the median palatal raphae, and shape of the dental arches were analyzed using Chi-square and Mann-Whitney tests between males and females. RESULTS: Wavy and curved patterns appeared to be most prevalent in both males and females but with no significant difference. The number of primary rugae in females and secondary rugae in males, on left side of the palate, was significantly more than their counterparts (P < 0.05). When rugae unification was observed, diverging type was significantly more in males than in females. Parabolic dental arch form, elliptical type of incisive papilla, and medium length of median palatal raphae was observed in majority of the subjects. CONCLUSION: The present study hypothesizes the uniqueness of the rugae in personal identification as no two palates showed similar type of rugae in either of the genders. The rugae pattern also contributes minimally towards sex determination as there was no significant difference observed between the two variables. PMID- 26816466 TI - Comparison of sexual dimorphism of permanent mandibular canine with mandibular first molar by odontometrics. AB - BACKGROUND AND OBJECTIVES: Sexual dimorphism is one of important tool of forensic science. The objective of this study is to assess the dimorphic status of mesio distal (MD) and bucco-lingual (BL) diameter of mandibular canine with mandibular first molar among the students of dental college. This study is of definite significance as sex chromosomes and hormonal production influenced tooth morphology. MATERIALS AND METHODS: The descriptive study adopted the purposive sampling technique, of 50 male and 50 female aged 17-25 years, using study casts for mesio-distal and bucco-lingual dimensions of mandibular canine with mandibular first molar were taken using digital Vernier caliper. The data obtained were subjected to statistical analysis using descriptive statistics and t-test to compare MD and BL dimensions in male and female populations and P <= 0.05 was found statistically significant. RESULTS: Sexual dimorphism can be predicted by measuring mesiodistal dimension of mandibular canine and mandibular first molar. The left mandibular canine showed more sexual dimorphism (12.66%) in comparison to left mandibular first molar (0.824%) only. Right mandibular canine showed greater dimorphism in MD dimensions (10.94%) in comparison to right mandibular first molar (6.96%). In bucco-lingual dimensions mandibular canine showed less variability when compared with mandibular first molar, thus our study showed more significance on mesio-distal dimensions of both teeth. CONCLUSION: The present study concludes statistically significant sexual dimorphism in mandibular canine over mandibular first molar on study casts. The MD dimensions in mandibular canine and mandibular first molar can help in determining sex and identification of unknown person. PMID- 26816467 TI - 3D evaluation of palatal rugae for human identification using digital study models. AB - BACKGROUND: While there is literature suggesting that the palatal rugae could be used for human identification, most of these studies use two-dimensional (2D) approach. AIM: The aims of this study were to evaluate palatal ruga patterns using three-dimensional (3D) digital models; compare the most clinically relevant digital model conversion techniques for identification of the palatal rugae; develop a protocol for overlay registration; determine changes in palatal ruga individual patterns through time; and investigate the efficiency and accuracy of 3D matching processes between different individuals' patterns. MATERIAL AND METHODS: Five cross sections in the anteroposterior dimension and four cross sections in the transverse dimension were computed which generated 18 2D variables. In addition, 13 3D variables were defined: The posterior point of incisive papilla (IP), and the most medial and lateral end points of the palatal rugae (R1MR, R1ML, R1LR, R1LL, R2MR, R2ML, R2LR, R2LL, R3MR, R3ML, R3LR, and R3LL). The deviation magnitude for each variable was statistically analyzed in this study. Five different data sets with the same 31 landmarks were evaluated in this study. RESULTS: The results demonstrated that 2D images and linear measurements in the anteroposterior and transverse dimensions were not sufficient for comparing different digital model conversion techniques using the palatal rugae. 3D digital models proved to be a highly effective tool in evaluating different palatal ruga patterns. The 3D landmarks showed no statistically significant mean differences over time or as a result of orthodontic treatment. No statistically significant mean differences were found between different digital model conversion techniques, that is, between OrthoCADTM and Ortho Insight 3DTM, and between Ortho Insight 3DTM and the iTero((r)) scans, when using 12 3D palatal rugae landmarks for comparison. CONCLUSION: Although 12 palatal 3D landmarks could be used for human identification, certain landmarks were especially important in the matching process and were arranged by strength and importance. Proposed values for 3D palatal landmarks were introduced that could be useful in biometrics and forensic odontology for the verification of human identity. PMID- 26816468 TI - Micro secure digital card. PMID- 26816470 TI - Erratum: Histological appearance of postmortem pink teeth: Report of two cases. AB - [This corrects the article on p. 168 in vol. 7, PMID: 26005309.]. PMID- 26816469 TI - Erratum: Comparison of palatal rugae patterns in Kodava and Malayalee populations of South India. AB - [This corrects the article on p. 85 in vol. 5, PMID: 24255555.]. PMID- 26816471 TI - Trivializing assessment: A key factor in undermining the standards of medical education. PMID- 26816472 TI - Vasorelaxation of goat mesenteric artery is mediated by endothelial Na(+)-K(+) ATPase. AB - OBJECTIVE: To examine the role of Na(+)-K(+)-ATPase and K(+) channels in mediating vasorelaxation in the superior mesenteric artery of Capra hircus. MATERIALS AND METHODS: Goat superior mesenteric artery (GSMA) was cut into 1.5-2 mm circular rings and mounted in a thermostatically controlled (37 degrees C +/- 0.5 degrees C) organ bath containing 20 ml of modified Krebs-Henseleit saline (MKHS) (pH 7.4), with continuous aeration under 1.5 g tension for 90 min. Endothelium-intact (ED+) or endothelium-denuded (ED-) GSMA ring was contracted with phenylephrine (PE) or 5-hydroxytryptamine (5-HT) (1 MUM-0.1 mM) in the absence or presence of ouabain (0.1 MUM). KCl (1 MUM-10 mM) was added cumulatively to K(+)-free MKHS-pre-contracted (ED+/-) rings in the absence or presence of ouabain (0.1 MUM) or barium (1 MUM) or 4-aminopyridine (1 MUM). RESULTS: Ouabain did not alter the basal tone of the arterial ring. The contractile response induced by PE (Emax: 50.46 +/- 2.68, pD2: 5.53 +/- 0.04) and 5-HT (Emax: 30.86 +/- 1.33, pD2: 6.17 +/- 0.03) in ED+ ring was significantly (P < 0.001) augmented in ED- rings (PE: Emax: 93.30 +/- 2.11, pD2: 6.41 +/- 0.04; 5 HT: Emax: 95.07 +/- 0.99, pD2: 6.27 +/- 0.03). The contractile response induced by PE and 5-HT in ED+ or ED- rings in the presence of ouabain was almost identical with that of ED- rings. Vasorelaxation of KCl (Emax: 2.90 +/- 1.14, pD2: 3.9 +/- 0.03) was significantly attenuated in the presence of ouabain (Emax: 73.8 +/- 5.16, pD2: 4.3 +/- 0.04), Ba(2+) (Emax: 16.34 +/- 4.7, pD2: 3.22 +/- 0.02), 4-AP (Emax: 18.16 +/- 2.4, pD2: 3.68 +/- 0.03), ouabain and Ba(2+) (Emax: 70.09 +/- 3.66, pD2: 4.41 +/- 0.04), and ouabain and 4-AP (Emax: 66.98 +/- 4.61, pD2: 4.13 +/- 0.06). CONCLUSION: The vasorelaxation in GSMA is mediated by the endothelium-derived hyperpolarizing factor (EDHFs) such as ouabain-sensitive Na(+)-K(+)-ATPase, KIR and Kv channels. PMID- 26816473 TI - Successful management of malignant hyperpyrexia syndrome in a pediatric patient: What to do when dantrolene is not available? AB - Malignant hyperpyrexia syndrome (MHS) is a rare entity and may not be encountered by the anaesthesiologists throughout their professional career. Whenever it manifests can be a challenging task to manage and prove to be fatal when a timely diagnosis and required therapeutic measures are not taken. Althoughthe dantrolene should be available wherever anaesthesia is practiced, considering the rarity of the syndrome this may not be the scenario always. We are reporting a case of MHS in a pediatric patient to highlight the facts that prompt clinical diagnosis, ongoing supportive treatment, discontinuation of all the anaesthetic agents and and stringent perioperative monitoring along with postoperative oral dantrolene may provide an answer to the MHS crisis in the face of an unavailability of the IV dantrolene; as may be the case in many rural and developing set-ups. PMID- 26816474 TI - Mirtazapine withdrawal-induced mania. AB - Antidepressant withdrawal mania is not a commonly reported occurrence. To date, there is only one published report of hypomanic episode on withdrawal of mirtazapine. A case is presented herein of a patient who experienced manic episode on withdrawal of mirtazapine. PMID- 26816475 TI - Carbamazepine-induced hypertension: A rare case. AB - A 74-year-old female with trigeminal neuralgia developed hypertension after the initiation of carbamazepine therapy. The time sequence of start of the suspected drug and onset of hypertension are consistent with the diagnosis. The hypertension did not resolve with antihypertensive therapy or dose reduction of carbamazepine. Patient recovered after the carbamazepine therapy was discontinued. The positive rechallenge and positive dechallenge showed association of carbamazepine therapy with hypertension as its adverse effect. This is a rare case that we report of carbamazepine-induced hypertension and this report may act as alerting mechanism to the health care professionals especially neurologists. PMID- 26816477 TI - Sodium thiosulfate for the treatment of warfarin-induced calciphylaxis in a nondialysis patient. AB - Calciphylaxis or uremic arteriolopathy is a complex process typically seen in patients with end-stage renal disease, but has also been reported in patients with normal renal function. However, therapies for calciphylaxis are based on reports of traditional patients (i.e., end-stage renal disease). A mainstay of therapy, sodium thiosulfate (STS), has been shown to be effective for the treatment of calciphylaxis. Without a standardized therapy reported for nondialysis patients there is a need for evidence-based therapy. Here, we report a case of a 63-year-old woman with an acute injury on chronic kidney disease (CrClBaseline = 48 mL/min, CrClAKI = 36 mL/min), not requiring dialysis, with warfarin-induced calciphylaxis. After 4 weeks of therapy with STS, sevelamer, alendronate, and enzymatic debridement the patient subjectively reported slight improvement of the necrotic ulcers but developed cellulitis on her nonaffected limb. Additionally, after 12 weeks of therapy she was readmitted for renal failure and subsequently required dialysis. PMID- 26816476 TI - A case of losartan-induced severe hyponatremia. AB - This case report outlines a very rare case of losartan-induced severe hyponatremia in a 73-year-old type 2 diabetic patient. The patient was initiated with 50 mg daily oral losartan monotherapy for newly diagnosed moderate hypertension. After 3.5 months of taking the drug, he presented to the emergency department in a drowsy state with severe generalized weakness and occasional palpitations. He was a known diabetic for the last 3 years and well controlled by oral metformin alone. On examination, his serum sodium level was found to be 123 meq/L. There were no evidences of any other possible metabolic, infective, organic or other pathologic causes giving rise to that condition, except losartan itself. De-challenge was done and he was treated vigorously resulting in reversal of the diseased state. Naranjo adverse drug reaction probability scale suggested that it was "probable" that oral losartan was responsible for the development of severe hyponatremia in this patient. PMID- 26816478 TI - Etoricoxib- induced pleural effusion: A case for rational use of analgesics. AB - Pleural effusion caused by drug is an uncommon event in clinical practice. Etoricoxib induced pleural effusion is an extremely rare. We describe a patient with pleural effusion as an adverse drug reaction of etoricoxib. PMID- 26816479 TI - Are we moving towards a new definition of essential medicines? PMID- 26816480 TI - Are we moving towards a new definition of essential medicines? PMID- 26816481 TI - Author's reply. PMID- 26816482 TI - An upcoming drug for onychomycosis: Tavaborole. AB - Fungal infection of the nail as well as nail bed is termed as 'onychomycosis'. It is caused by dermatophytes, non-dermatophytic fungal species and yeasts like Candida albicans. It is traditionally treated by topical antifungals, systemic agents like ketoconazole, griseofulvin, itraconazole, fluconazole, etc. Chemical avulsion or surgical removal of nail can also be tried to treat this disease. In spite of all these treatment options available, podiatrists were always in search of an ideal drug molecule with lesser side effects and which may improve the patient compliance. This exhaustive search led to the discovery of a better antifungal agent, known as "Tavaborole." A systematic literature search was carried out using databases such as PubMed, Cochrane Reviews, Google Scholar, etc. Detailed information about onychomycosis and tavaborole was gathered. Tavaborole is the first oxaborole antifungal agent approved by FDA in July 2014. It is marketed under the trade name "Kerydin." It acts by inhibiting protein synthesis in the fungus. It inhibits an enzyme known as cytosolic leucyl-transfer RNA synthetase, or LeuRS, which plays a key role in fungal essential protein synthesis. Dermatitis at the site of topical application, erythema, exfoliation and ingrowing toe nail has been reported in 1% of subjects. Tavaborole may offer a promising role in the treatment of onychomycosis and may compell podiatrists to offer its use in onychomycosis. The present study describes about chemical nature, mechanism of action and two completed phase 3 clinical trial findings of Tavaborole. PMID- 26816483 TI - Erratum: Inhaled insulin: A "puff" than a "shot" before meals. AB - [This corrects the article on p. 126 in vol. 6, PMID: 26311994.]. PMID- 26816484 TI - Assessment of Navel Oranges, Clementine Tangerines, and Rutaceous Fruits as Hosts of Bactrocera cucurbitae and Bactrocera latifrons (Diptera: Tephritidae). AB - Export of Citrus spp. fruits may require risk mitigation measures if grown in areas with established tephritid fruit fly (Diptera: Tephritidae) populations capable of infesting the fruits. The host status of Citrus spp. fruits is unclear for two tephritid fruit fly species whose geographic ranges have expanded in recent years: melon fly, Bactrocera cucurbitae (Cocquillett), and Bactrocera latifrons (Hendel). In no choice cage infestation studies, B. latifrons oviposited into intact and punctured Washington navel oranges (Citrus sinensis [L.] Osbeck) and Clementine tangerines (C. reticulata L. var. Clementine), but eggs rarely developed to the adult stage. B. cucurbitae readily infested intact and punctured tangerines, and to a lesser extent punctured oranges, but did not infest intact oranges. Limited cage infestation and only a single literature report of field Citrus spp. infestation suggest that risk mitigation of Citrus spp. for B. latifrons is not needed. Risk mitigation options of Citrus spp. for B. cucurbitae, including heat and cold treatments and systems approaches, are discussed. PMID- 26816485 TI - Oxidative Damaged Products, Level of Hydrogen Peroxide, and Antioxidant Protection in Diapausing Pupa of Tasar Silk Worm, Antheraea mylitta: A Comparative Study in Two Voltine Groups. AB - The present study demonstrates tissue-specific (hemolymph and fat body) and inter voltine [bivoltine (BV) and trivoltine (TV)] differences in oxidatively damaged products, H2O2 content, and the relative level of antioxidant protection in the diapausing pupae of Antheraea mylitta. Results suggest that fat body (FB) of both the voltine groups has oxidative predominance, as evident from the high value of lipid peroxidation and H2O2 content, despite better enzymatic defenses in comparison to hemolymph (HL). This may be attributed to the higher metabolic rate of the tissue concerned, concomitant with high lipid content and abundance of polyunsaturated fatty acids (PUFA). Nondetectable catalase activity in the pupal hemolymph of both strains apparently suggests an additional mechanism for H2O2 metabolism in the tissue. Inter-voltine comparison of the oxidative stress indices and antioxidant defense potential revealed that the TV group has a higher oxidative burden, lower activities for the antioxidant enzymes, and compensatory nonenzymatic protection from reduced glutathione and ascorbic acid. PMID- 26816486 TI - Stable Fly, Stomoxys calcitrans (L.), Dispersal and Governing Factors. AB - Although the movement of stable fly, Stomoxys calcitrans (L.), has been studied, its extent and significance has been uncertain. On a local scale (<13 km), fly movement occurs between host animals and resting sites to feed and mate, mainly at on-farm locations where herbivorous livestock regularly congregate. Small numbers emigrate from livestock congregation sites in search of other hosts and oviposition substrate, mostly within <1.6 km. Such local movement occurs by flight ~90 cm above ground, or with moving livestock. While stable flies are active year-round in warm latitudes, cold winters in temperate areas result in substantial population and activity declines, limiting movement of any sort to warmer seasons. Long-distance dispersal (>13 km) is mainly wind-driven by weather fronts that carry stable flies from inland farm areas for up to 225 km to beaches of northwestern Florida and Lake Superior. Stable flies can reproduce for a short time each year in washed-up sea grass, but the beaches are not conducive to establishment. Such movement is passive and does not appear to be advantageous to stable fly's survival. On a regional scale, stable flies exhibit little genetic differentiation, and on the global scale, while there might be more than one "lineage", the species is nevertheless considered to be panmictic. Population expansion across much of the globe likely occurred from the late Pleistocene to the early Holocene in association with the spread of domesticated nomad livestock and particularly with more sedentary, penned livestock. PMID- 26816487 TI - Melon Fly, Bactrocera cucurbitae (Diptera: Tephritidae), Infestation in Host Fruits in the Southwestern Islands of Japan Before the Initiation of Island-wide Population Suppression, as Recorded in Publications of Japanese Public Institutions. AB - Bactrocera cucurbitae (Coquillett) is a tephritid fruit fly native to the Indo Malayan region. Its distribution, though, has extended to include Africa, temperate Asia, and a number of Pacific islands. It became established in Japan in 1919 in the Yaeyama Islands and spread north in the Southwestern Islands of Japan. It was subsequently eradicated from these islands by an eradication program that extended from 1972 to 1993. As part of an effort to develop a worldwide database on the status of fruits as hosts of melon fly, the infestation data gathered from host fruits collected in this eradication program, before the initiation of suppression activities, are summarized here. Bactrocera cucurbitae infestation was documented in 24 plant taxa of four plant families (Caricaceae, Cucurbitaceae, Moraceae, and Solanaceae), with the following four new hosts identified: Ficus erecta Thunb., F. pumila L. (Moraceae), Solanum erianthum D. Don (Solanaceae), and Zehneria liukiuensis Jeffrey ex Walker (Cucurbitaceae). PMID- 26816488 TI - Efficacy of Bacillus thuringiensis (var. kurstaki) Against Diamondback Moth (Plutella xylostella L.) Eggs and Larvae on Cabbage Under Semi-Controlled Greenhouse Conditions. AB - The efficacy of Bacillus thuringiensis (var. kurstaki) (Btk) against the diamondback moth (DBM) on cabbage was studied at Botswana College of Agriculture, Gaborone, Botswana. Using five concentrations of Btk: 2, 4, 6, 8, and 10 g/L, bioassays were conducted against DBM eggs and second instar larvae at 30 degrees C +/- 5 degrees C. Each treatment was replicated three times. Probit analysis was used to determine the LD50 and LD90 values for the treatments against eggs and larvae. When the treatments were assessed at 72, 96, 120, and 144 hours, LD90 values against larvae were 11.02, 10.22, 5.92, and 4.01 g/L, whereas they were 7.71, 6.94, and 6.24 g/L against eggs when assessed 48, 72, and 96 hours after the expected time of hatching. This indicated that Btk was effective against both eggs and larvae when exposed for long periods. The slopes of the probit lines for larvae assessed at 24, 48, 72, 96, 120, and 144 hours after application were 0.250, 1.064, 0.910, 0.383, 0.453, and 0.414, while those against eggs were 1.153, 1.246, and 0.933 when assessed 48, 72, and 96 hours after the expected time of hatching. This indicates a smaller change in mortality with increase in pesticide dosage for both eggs and larvae. Btk treatments achieved 85.7%-94.6% reduction in DBM damage on cabbage. Therefore, Btk can be used to achieve effective control of DBM eggs and larvae and reduce damage on cabbage under greenhouse conditions. PMID- 26816489 TI - Resistance Level of Mosquito Species (Diptera: Culicidae) from Shandong Province, China. AB - This study describes the aquatic habitats, species composition, and the insecticide resistance level of the mosquito Culex pipiens pallens in Shandong Province, China. A cross-sectional survey of mosquito larval habitats was conducted from May to November 2014 to determine the species composition and larval abundance. Larvae were collected using the standard dipping technique, and a total of four habitat types were sampled. The fourth instar larvae of Cx. pipiens pallens collected in each habitat type were tested for resistance to five insecticides according to a WHO bioassay. A total of 7,281 mosquito larvae were collected, of which 399 (5.48%) were categorized as Anopheles mosquito larvae (An. sinensis), 6636 (91.14%) as culicine larvae (Cx. pipiens pallens, Cx. tritaeniorhynchus, Cx. halifaxii, and Cx. bitaeniorhynchus), 213 (2.93%) as Armigeres larvae, and 33 (0.45%) as Aedes larvae (Aedes albopictus). In addition, a total of 1,149 mosquito pupae were collected. Culex larvae were distributed in all habitats investigated. Tukeys HSD analysis showed that roadside drainages were the most productive habitat type for Culex larvae. Armigeres species were found only in drains, Aedes only in water tanks, and Anopheles in water that was comparatively clear and rich in emergent plants. Bioassay showed that the maximum resistance level of Cx. pipiens pallens was to deltamethrin, while it was lowest to plifenate. The productivity of various mosquitoes in different habitat types is very heterogeneous. It is particularly important to modify human activity and the environment to achieve effective mosquito vector control. For effective larval control, the type of habitat should be considered, and the most productive habitat type should be given priority in mosquito abatement programs. PMID- 26816490 TI - The Prodomain-Containing BMP9 Produced from a Stable Line Effectively Regulates the Differentiation of Mesenchymal Stem Cells. AB - BACKGROUND: BMPs play important roles in regulating stem cell proliferation and differentiation. Using adenovirus-mediated expression of the 14 types of BMPs we demonstrated that BMP9 is one of the most potent BMPs in inducing osteogenic differentiation of mesenchymal stem cells (MSCs), which was undetected in the early studies using recombinant BMP9 proteins. Endogenous BMPs are expressed as a precursor protein that contains an N-terminal signal peptide, a prodomain and a C terminal mature peptide. Most commercially available recombinant BMP9 proteins are purified from the cells expressing the mature peptide. It is unclear how effectively these recombinant BMP9 proteins functionally recapitulate endogenous BMP9. METHODS: A stable cell line expressing the full coding region of mouse BMP9 was established in HEK-293 cells by using the piggyBac transposon system. The biological activities and stability of the conditioned medium generated from the stable line were analyzed. RESULTS: The stable HEK-293 line expresses a high level of mouse BMP9. BMP9 conditioned medium (BMP9-cm) was shown to effectively induce osteogenic differentiation of MSCs, to activate BMP-R specific Smad signaling, and to up-regulate downstream target genes in MSCs. The biological activity of BMP9-cm is at least comparable with that induced by AdBMP9 in vitro. Furthermore, BMP9-cm exhibits an excellent stability profile as its biological activity is not affected by long-term storage at -80oC, repeated thawing cycles, and extended storage at 4oC. CONCLUSIONS: We have established a producer line that stably expresses a high level of active BMP9 protein. Such producer line should be a valuable resource for generating biologically active BMP9 protein for studying BMP9 signaling mechanism and functions. PMID- 26816491 TI - Predicting Acute Kidney Injury Following Mitral Valve Repair. AB - BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is associated with short-term and long-term adverse outcomes. Novel biomarkers have been identified for the early detection of AKI; however, examining these in every patient who undergoes cardiac surgery is prohibitively expensive. Society of Thoracic Surgeons (STS) and Age, Creatinine, and Ejection Fraction (ACEF) scores have been proven to predict mortality in bypass surgery. The aim of this study was to determine whether these scores can be used to predict AKI after mitral valve repair. MATERIALS AND METHODS: Between January 2010 and December 2013, 196 patients who underwent mitral valve repair were enrolled. The clinical characteristics, outcomes, and scores of prognostic models were collected. The primary outcome was postoperative AKI, defined using the Kidney Disease Improving Global Outcome 2012 clinical practice guidelines for AKI. RESULTS: A total of 76 patients (38.7%) developed postoperative AKI. The STS renal failure (AUROC: 0.797, P < .001) and ACEF scores (AUROC: 0.758, P < .001) are both satisfactory tools for predicting all AKI. The STS renal failure score exhibited superior accuracy compared with the ACEF score in predicting AKI stage 2 and 3. The overall accuracy of both scores was similar for all AKI and AKI stage 2 and 3 when the cut-off points of the STS renal failure and ACEF scores were 2.2 and 1.1, respectively. CONCLUSION: In conclusion, the STS renal failure score can be used to accurately predict stage 2 and 3 AKI after mitral valve repair. The ACEF score is a simple tool with satisfactory power in screening patients at risk of all AKI stages. Additional studies can aim to determine the clinical implications of combining preoperative risk stratification and novel biomarkers. PMID- 26816495 TI - Rapid, Effective DNA Isolation from Osmanthus via Modified Alkaline Lysis. AB - Variability of leaf structure and presence of secondary metabolites in mature leaf tissue present a challenge for reliable DNA extraction from Osmanthus species and cultivars. The objective of this study was to develop a universal rapid, effective, and cost-efficient method of DNA isolation for Osmanthus mature leaf tissue. Four different methods were used to isolate DNA from 8 cultivars of Osmanthus. Absorbance spectra, DNA concentration, appearance on agarose gel, and performance in PCR were used to analyze quality, quantity, and integrity of isolated DNA. Methods were ranked in order, based on total quantity, quality, and performance points as the following: 1) solid-phase extraction (SPE), 2) modified alkaline lysis (SDS), 3) cetyltrimethylammonium bromide (CTAB) with chloroform (CHL), and 4) CTAB with phenol/chloroform (PHE). Total DNA, isolated via SPE, showed the least contamination but the lowest mean quantity (9.6 +/- 3.4 MUg) and highest cost. The highest quantity of DNA was isolated via SDS (117 +/- 54.1 MUg). SPE and SDS resolved the most individuals on agarose gel, whereas the 2 CTAB methods had poorly resolved gels. All methods except PHE performed well in PCR. Additions to the modified alkaline lysis method increased A260:A230 by up to 59% without affecting yield. With the use of SDS, an average of 1000 MUg/g DNA was isolated from fresh leaf tissue of 18 samples in ~1.5 h at a cost of 0.74 U.S. dollars (USD)/sample. We recommend improved alkaline lysis as a rapid, effective, and cost-efficient method of isolating DNA from Osmanthus species. PMID- 26816492 TI - Systematic Review of Metabolic Syndrome Biomarkers: A Panel for Early Detection, Management, and Risk Stratification in the West Virginian Population. AB - INTRODUCTION: Metabolic syndrome represents a cluster of related metabolic abnormalities, including central obesity, hypertension, dyslipidemia, hyperglycemia, and insulin resistance, with central obesity and insulin resistance in particular recognized as causative factors. These metabolic derangements present significant risk factors for cardiovascular disease, which is commonly recognized as the primary clinical outcome, although other outcomes are possible. Metabolic syndrome is a progressive condition that encompasses a wide array of disorders with specific metabolic abnormalities presenting at different times. These abnormalities can be detected and monitored via serum biomarkers. This review will compile a list of promising biomarkers that are associated with metabolic syndrome and this panel can aid in early detection and management of metabolic syndrome in high risk populations, such as in West Virginia. METHODS: A literature review was conducted using PubMed, Science Direct, and Google Scholar to search for markers related to metabolic syndrome. Biomarkers searched included adipokines (leptin, adiponectin), neuropeptides (ghrelin), pro-inflammatory cytokines (IL-6, TNF-alpha), anti-inflammatory cytokines (IL-10), markers of antioxidant status (OxLDL, PON-1, uric acid), and prothrombic factors (PAI-1). RESULTS: According to the literature, the concentrations of pro-inflammatory cytokines (IL-6, TNF-alpha), markers of pro oxidant status (OxLDL, uric acid), and prothrombic factors (PAI-1) were elevated in metabolic syndrome. Additionally, leptin concentrations were found to be elevated in metabolic syndrome as well, likely due to leptin resistance. In contrast, concentrations of anti-inflammatory cytokines (IL-10), ghrelin, adiponectin, and antioxidant factors (PON-1) were decreased in metabolic syndrome, and these decreases also correlated with specific disorders within the cluster. CONCLUSION: Based on the evidence presented within the literature, the aforementioned biomarkers correlate significantly with metabolic syndrome and could provide a minimally-invasive means for early detection and specific treatment of these disorders. Further research is encouraged to determine the efficacy of applying these biomarkers to diagnosis and treatment in a clinical setting. PMID- 26816493 TI - The Association of Mitofusion-2 Gene Polymorphisms with Susceptibility of Essential Hypertension in Northern Han Chinese Population. AB - BACKGROUND: Mitofusion-2 (Mfn2) played an important role in regulating vascular smooth muscle cells proliferation, insulin resistance and endoplasmic reticulum stress, which were found to be involved in the development of hypertension. So we inferred that the Mfn2 gene may participate in the pathogenesis of hypertension. The aim of this study was to determine whether common single nucleotide polymorphisms (SNPs) in Mfn2 gene were associated with essential hypertension (EH) in northern Han Chinese. METHODS: We genotyped 6 tagging SNPs of Mfn2 gene (rs2336384, rs2295281, rs17037564, rs2236057, rs2236058 and rs3766741) with the TaqMan assay in 626 hypertensive patients and 618 controls. RESULTS: Logistic regression analysis indicated that CC+CA genotype of rs2336384 and AA+AG genotype of rs2236057 were significantly associated with increased risk of EH (OR=1.617, P=0.005; OR=1.418, P=0.031, respectively). GG genotype of rs2236058 and GG+CG genotype of rs3766741 were found to be significantly associated with decreased risk of EH (OR=0.662, P=0.023; OR=0.639, P=0.024).When stratified by gender, for rs2336384, rs2236057 and rs2236058, significant association was observed in males, but not in females. Haplotype analysis indicated that the CCAACC haplotype was positively correlated with EH and there was a negative correlation between ACAGGG haplotype and EH. CONCLUSIONS: This study demonstrated that Mfn2 gene polymorphisms were associated with essential hypertension in northern Han Chinese population, especially in male subjects. PMID- 26816494 TI - Inverse Association between Sodium Channel-Blocking Antiepileptic Drug Use and Cancer: Data Mining of Spontaneous Reporting and Claims Databases. AB - PURPOSE: Voltage-gated sodium channels (VGSCs) are drug targets for the treatment of epilepsy. Recently, a decreased risk of cancer associated with sodium channel blocking antiepileptic drugs (AEDs) has become a research focus of interest. The purpose of this study was to test the hypothesis that the use of sodium channel blocking AEDs are inversely associated with cancer, using different methodologies, algorithms, and databases. METHODS: A total of 65,146,507 drug reaction pairs from the first quarter of 2004 through the end of 2013 were downloaded from the US Food and Drug Administration Adverse Event Reporting System. The reporting odds ratio (ROR) and information component (IC) were used to detect an inverse association between AEDs and cancer. Upper limits of the 95% confidence interval (CI) of < 1 and < 0 for the ROR and IC, respectively, signified inverse associations. Furthermore, using a claims database, which contains 3 million insured persons, an event sequence symmetry analysis (ESSA) was performed to identify an inverse association between AEDs and cancer over the period of January 2005 to May 2014. The upper limit of the 95% CI of adjusted sequence ratio (ASR) < 1 signified an inverse association. RESULTS: In the FAERS database analyses, significant inverse associations were found between sodium channel-blocking AEDs and individual cancers. In the claims database analyses, sodium channel-blocking AED use was inversely associated with diagnoses of colorectal cancer, lung cancer, gastric cancer, and hematological malignancies, with ASRs of 0.72 (95% CI: 0.60 - 0.86), 0.65 (0.51 - 0.81), 0.80 (0.65 - 0.98), and 0.50 (0.37 - 0.66), respectively. Positive associations between sodium channel-blocking AEDs and cancer were not found in the study. CONCLUSION: Multi methodological approaches using different methodologies, algorithms, and databases suggest that sodium channel-blocking AED use is inversely associated with colorectal cancer, lung cancer, gastric cancer, and hematological malignancies. PMID- 26816496 TI - Bone and Muscle Pleiotropy: The Genetics of Associated Traits. AB - Bone and muscle mass are highly correlated. In part, this is a consequence of both tissues sharing common genetic determinants. In addition, both tissues are responsive to their mechanical environments. New genetic tools in mice will allow genes of interest to be inactivated in experimentally defined contexts, thus allowing investigators to distinguish direct effects on each tissue from physiological responses to a primary phenotype in the other. PMID- 26816497 TI - Reliability and day-to-day variability of peak fat oxidation during treadmill ergometry. AB - BACKGROUND: Exercising at intensities where fat oxidation rates are high has been shown to induce metabolic benefits in recreational and health-oriented sportsmen. The exercise intensity (Fatpeak) eliciting peak fat oxidation rates is therefore of particular interest when aiming to prescribe exercise for the purpose of fat oxidation and related metabolic effects. Although running and walking are feasible and popular among the target population, no reliable protocols are available to assess Fatpeak as well as its actual velocity (VPFO) during treadmill ergometry. Our purpose was therefore, to assess the reliability and day to-day variability of VPFO and Fatpeak during treadmill ergometry running. METHODS: Sixteen recreational athletes (f = 7, m = 9; 25 +/- 3 y; 1.76 +/- 0.09 m; 68.3 +/- 13.7 kg; 23.1 +/- 2.9 kg/m(2)) performed 2 different running protocols on 3 different days with standardized nutrition the day before testing. At day 1, peak oxygen uptake (VO2peak) and the velocities at the aerobic threshold (VLT) and respiratory exchange ratio (RER) of 1.00 (VRER) were assessed. At days 2 and 3, subjects ran an identical submaximal incremental test (Fat-peak test) composed of a 10 min warm-up (70 % VLT) followed by 5 stages of 6 min with equal increments (stage 1 = VLT, stage 5 = VRER). Breath-by-breath gas exchange data was measured continuously and used to determine fat oxidation rates. A third order polynomial function was used to identify VPFO and subsequently Fatpeak. The reproducibility and variability of variables was verified with an intraclass correlation coefficient (ICC), Pearson's correlation coefficient, coefficient of variation (CV) and the mean differences (bias) +/- 95 % limits of agreement (LoA). RESULTS: ICC, Pearson's correlation and CV for VPFO and Fatpeak were 0.98, 0.97, 5.0 %; and 0.90, 0.81, 7.0 %, respectively. Bias +/- 95 % LoA was -0.3 +/- 0.9 km/h for VPFO and -2 +/- 8 % of VO2peak for Fatpeak. CONCLUSION: In summary, relative and absolute reliability indicators for VPFO and Fatpeak were found to be excellent. The observed LoA may now serve as a basis for future training prescriptions, although fat oxidation rates at prolonged exercise bouts at this intensity still need to be investigated. PMID- 26816498 TI - On frogs, toxins and true friendship: an atypical case report. AB - The authors report a series of events including the scientific interest for poisonous dendrobates of French Guiana, the human confrontation with the immensity of the evergreen rainforest, the fragility of the best-prepared individuals to a rough life, and the unique and very special manifestation of a solid friendship between two experts and enthusiasts of outdoor life. In the evergreen forest of South America, as in many other scientific field expeditions, everything may suddenly go wrong, and nothing can prepare researchers to accidents that may occur in a succession of uncontrollable errors once the first mistake is done. This is what happened during an expedition in search for dendrobates by an experienced forest guide and naturalist. The authors decided to report the story, considering that it deserved to be brought to the attention of those interested in venomous animals and toxins, in order to illustrate the potential danger of dealing with these organisms. PMID- 26816499 TI - Dosimetric considerations and early clinical experience of accelerated partial breast irradiation using multi-lumen applicators in the setting of breast augmentation. AB - PURPOSE: Accelerated partial breast irradiation (APBI) is an accepted treatment option in breast-conserving therapy for early stage breast cancer. However, data regarding outcomes of patients treated with multi-lumen catheter systems who have existing breast implants is limited. The purpose of this study was to report treatment parameters, outcomes, and possible dosimetric correlation with cosmetic outcome for this population of patients at our institution. MATERIAL AND METHODS: We report the treatment and outcome of seven consecutive patients with existing breast implants and early stage breast cancer who were treated between 2009 and 2013 using APBI following lumpectomy. All patients were treated twice per day for five days to a total dose of 34 Gy using a high-dose-rate (192)Ir source. Cosmetic outcomes were evaluated using the Harvard breast cosmesis scale, and late toxicities were reported using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity schema. RESULTS: After a mean follow-up of 32 months, all patients have remained cancer free. Six out of seven patients had an excellent or good cosmetic outcome. There were no grade 3 or 4 late toxicities. The average total breast implant volume was 279.3 cc, received an average mean dose of 12.1 Gy, and a maximum dose of 234.1 Gy. The average percentage of breast implant volume receiving 50%, 75%, 100%, 150%, and 200% of the prescribed dose was 15.6%, 7.03%, 4.6%, 1.58%, and 0.46%, respectively. Absolute volume of breast implants receiving more than 50% of prescribed dose correlated with worse cosmetic outcomes. CONCLUSIONS: Accelerated partial breast irradiation using a multi-lumen applicator in patients with existing breast implants can safely be performed with promising early clinical results. The presence of the implant did not compromise the ability to achieve dosimetric criteria; however, dose to the implant and the irradiated implant volume may be related with worse cosmetic outcomes. PMID- 26816500 TI - Non-melanoma skin cancer treated with high-dose-rate brachytherapy and Valencia applicator in elderly patients: a retrospective case series. AB - PURPOSE: The incidence of non-melanoma skin cancer (NMSC) has been increasing over the past 30 years. Basal cell carcinoma and squamous cell carcinoma are the two most common subtypes of NMSC. The aim of this study was to estimate tumour control, toxicity, and aesthetic events in elderly patients treated with high dose-rate (HDR) brachytherapy (BT) using Valencia applicator. MATERIAL AND METHODS: From January 2012 to May 2015, 57 lesions in 39 elderly eligible patients were enrolled. All the lesions had a diameter <= 25 mm (median: 12.5 mm) and a depth <= 4 mm. The appropriate Valencia applicator, 2 or 3 cm in diameter was used. The prescribed dose was 40 Gy in 8 fractions (5 Gy/fraction) in 48 lesions (group A), and 50 Gy in 10 fractions (5 Gy/fraction) in 9 lesions (group B), delivered 2/3 times a week. The biological effective dose (BED) was 60 Gy and 75 Gy, respectively. RESULTS: After median follow-up of 12 months, 96.25% lesions showed a complete response and only two cases presented partial remission. Radiation Therapy Oncology Group - European Organization for Research and Treatment of Cancer (RTOG/EORTC) G 1-2 acute toxicities were observed in 63.2% of the lesions: 56.3% in group A and 77.7% in group B. Late G1-G2 toxicities was observed in 19.3% of the lesions: 18.8% in group A and 22.2% in group B, respectively. No G3 or higher acute or late toxicities occurred. In 86% of the lesions, an excellent cosmetic result was observed (87.5% in group A and 77.8% in group B). Six lesions had a good cosmetic outcome and only 2.3% presented a fair cosmetic impact. CONCLUSIONS: The treatment of NMSC with HDR-BT using Valencia surface applicator is effective with excellent and good cosmetics results in elderly patients. The hypofractionated course appears effective and no statistical differences were observed between the two groups analysed. PMID- 26816501 TI - Cesium-131 brachytherapy in high risk and recurrent head and neck cancers: first report of long-term outcomes. AB - PURPOSE: The feasibility and efficacy of re-irradiation using contemporary radiation techniques to treat recurrent head and neck cancer has been demonstrated but the role of brachytherapy is unclear. Here we describe the use of (131)Cs brachytherapy with concurrent salvage surgery in 18 patients. MATERIAL AND METHODS: Eligible patients underwent maximal gross resection of the tumor with implantation of brachytherapy seeds delivering a minimum dose of 80 Gy to the tumor bed. Rates of overall survival, locoregional progression free survival, disease-free survival, and radiation-induced toxicity were analyzed. RESULTS: Retrospective Kaplan-Meier analysis shows median overall survival was 15 months and disease free survival was 12 months. Two patients developed grade 3 toxicity; all other complications were grade 1-2 with no grade 4 or 5 complications. CONCLUSIONS: Compared to prior literature, our study shows comparable rates of survival with a decreased rate of radiation-induced toxicity. PMID- 26816502 TI - Combined brachytherapy and external beam radiation: an effective approach for palliation in esophageal cancer. AB - PURPOSE: Palliation of dysphagia is a challenge in advanced esophageal cancer. The addition of external beam radiotherapy (EBRT) to intraluminal brachytherapy (ILBT) has shown significant improvement in dysphagia relief and symptom scores. The aim of the present study was to evaluate the efficacy of combined use of ILBT and EBRT. MATERIAL AND METHODS: The medical records of 148 patients with advanced/metastatic esophageal cancer were screened from January 2008 to April 2014, and 74 patients were found eligible for the analysis. All patients received two fractions of 8 Gy each of ILBT, followed by EBRT. Patients were assessed for the symptom scores of dysphagia, odynophagia, regurgitation, and chest pain and weight was recorded periodically. RESULTS: For a median follow-up of 6 months, the median OS was 9.5 months (95% CI: 7.5-10.5). The median dysphagia free survival was 6 months (95% CI: 4.8-7.1). The scores for dysphagia significantly improved after completion of 1(st) ILBT (p = 0.000), 2(nd) ILBT (p = 0.000), and at 3 months after EBRT compared to ILBT (p = 0.02). Overall 47% had improvement in dysphagia scores and 35% maintained the improvement of scores till last follow up. There was significant improvement in weight after completion of ILBT (p = 0.001) and at 3 months after completion of EBRT (p = 0.00). Twenty nine (39%) patients required nasogastric (NGT) insertions and 12 (16%) needed hospitalization for supportive care. 36.4% had complications in the form of stricture (27%), fistula (5.4%), and bleeding (4%). CONCLUSIONS: Palliative radiotherapy is an effective alternative for palliation of dysphagia with improvement in symptom scores being evident and sustained. The results of this clinical audit were comparable with those from the trial setting. PMID- 26816503 TI - Attitude and practice of brachytherapy in India: a study based on the survey amongst attendees of Annual Meeting of Indian Brachytherapy Society. AB - PURPOSE: We performed a survey amongst attendees of the 4(th) Annual Meeting of Indian Brachytherapy Society to study the patterns of brachytherapy practice and attitude towards brachytherapy use. MATERIAL AND METHODS: A 19-point questionnaire was designed and e-mailed to the attendees immediately after the conference. Descriptive analysis of the responses were done and satisfaction index was used as a tool for evaluation of the program effectiveness. Binomial test was used to assess the difference between distributions of responses and Mann-Whitney U test was used to assess the correlation between responses. P value (2-tailed) of < 0.05 was taken significant for all statistical analysis. RESULTS: Of a total of 202 attendees, 90 responded to the survey (response rate: 44.5%). Seventy-two percent belonged to an academic institute while 28% belonged to non academic institutes. Eighty-six percent were radiation oncologists and 10% were medical physicists. Eighty-nine percent respondents used high-dose-rate, 14% - pulse-dose-rate, and 13% used low-dose-rate brachytherapy facility. Orthogonal X rays, computed tomography, and magnetic resonance imaging was used for brachytherapy planning by 56%, 69%, and 14%, respectively. Ninety-three percent of them thought that lack of training is a hurdle in practicing brachytherapy and 92% opined that brachytherapy dedicated meetings can change their perception about brachytherapy. Seventy percent respondents admitted to make some changes in their practice patterns after attending this meeting. Ninety-seven percent of them would like to attend future meetings and 98% felt the need to include live workshops, hands on demonstrations, and video presentations in the scientific programme. CONCLUSIONS: The survey highlights a positive attitude towards increasing brachytherapy use, and may serve as an important guiding tool in designing teaching and training programmes; thus overcoming the hurdles in successful and widespread use of a quality brachytherapy programme at radiotherapy centers. PMID- 26816504 TI - Evaluation of BEBIG HDR (60)Co system for non-invasive image-guided breast brachytherapy. AB - PURPOSE: HDR (60)Co system has recently been developed and utilized for brachytherapy in many countries outside of the U.S. as an alternative to (192)Ir. In addition, the AccuBoost((r)) technique has been demonstrated to be a successful non-invasive image-guided breast brachytherapy treatment option. The goal of this project is to evaluate the possibility of utilizing the BEBIG HDR (60)Co system for AccuBoost treatment. These evaluations are performed with Monte Carlo (MC) simulation technique. MATERIAL AND METHODS: In this project, the MC calculated dose distributions from HDR (60)Co for various breast sizes have been compared with the simulated data using an HDR (192)Ir source. These calculations were performed using the MCNP5 code. The initial calculations were made with the same applicator dimensions as the ones used with the HDR (192)Ir system (referred here after as standard applicator). The activity of the (60)Co source was selected such that the dose at the center of the breast would be the same as the values from the (192)Ir source. Then, the applicator wall-thickness for the HDR (60)Co system was increased to diminish skin dose to levels received when using the HDR (192)Ir system. With this geometry, dose values to the chest wall and the skin were evaluated. Finally, the impact of a conical attenuator with the modified applicator for the HDR (60)Co system was analyzed. RESULTS: These investigations demonstrated that loading the (60)Co sources inside the thick walled applicators created similar dose distributions to those of the (192)Ir source in the standard applicators. However, dose to the chest wall and breast skin with (60)Co source was reduced using the thick-walled applicators relative to the standard applicators. The applicators with conical attenuator reduced the skin dose for both source types. CONCLUSIONS: The AccuBoost treatment can be performed with the (60)Co source and thick-wall applicators instead of (192)Ir with standard applicators. PMID- 26816505 TI - Transition from Paris dosimetry system to 3D image-guided planning in interstitial breast brachytherapy. AB - PURPOSE: The purpose of this study is to evaluate our first experience with 3D image-guided breast brachytherapy and to compare dose distribution parameters between Paris dosimetry system (PDS) and image-based plans. MATERIAL AND METHODS: First 49 breast cancer patients treated with 3D high-dose-rate interstitial brachytherapy as a boost were selected for the study. Every patient underwent computed tomography, and the planning target volume (PTV) and organs at risk (OAR) were outlined. Two treatment plans were created for every patient. First, based on a Paris dosimetry system (PDS), and the second one, imaged-based plan with graphical optimization (OPT). The reference isodose in PDS implants was 85%, whereas in OPT plans the isodose was chosen to obtain proper target coverage. Dose and volume parameters (D90, D100, V90, V100), doses at OARs, total reference air kerma (TRAK), and quality assurance parameters: dose nonuniformity ratio (DNR), dose homogeneity index (DHI), and conformity index (COIN) were used for a comparison of both plans. RESULTS: The mean number of catheters was 7 but the mean for 20 first patients was 5 and almost 9 for the next 29 patients. The mean value of prescribed isodose for OPT plans was 73%. The mean D90 was 88.2% and 105.8%, the D100 was 59.8% and 75.7%, the VPTV90 was 88.6% and 98.1%, the VPTV100 was 79.9% and 98.9%, and the TRAK was 0.00375 Gym(-1) and 0.00439 Gym(-1) for the PDS and OPT plans, respectively. The mean DNR was 0.29 and 0.42, the DHI was 0.71 and 0.58, and the COIN was 0.68 and 0.76, respectively. CONCLUSIONS: The target coverage in image-guided plans (OPT) was significantly higher than in PDS plans but the dose homogeneity was worse. Also, the value of TRAK increased because of change of prescribing isodose. The learning curve slightly affected our results. PMID- 26816506 TI - Comparison of doses to the rectum derived from treatment planning system with in vivo dose values in vaginal vault brachytherapy using cylinder applicators. AB - PURPOSE: In-vivo measurements to determine doses to organs-at-risk can be an essential part of brachytherapy quality assurance (QA). This study compares calculated doses to the rectum with measured dose values as a means of QA in vaginal vault brachytherapy using cylinder applicators. MATERIAL AND METHODS: At the Department of Radiotherapy, University College Hospital (UCH), Ibadan, Nigeria, intracavitary brachytherapy (ICBT) was delivered by a GyneSource high dose-rate (HDR) unit with (60)Co. Standard 2D treatment plans were created with HDR basic 2.6 software for prescription doses 5-7 Gy at points 5 mm away from the posterior surface of vaginal cylinder applicators (20, 25, and 30 mm diameters). The LiF:Mg, Ti thermoluminescent dosimeter rods (1 x 6 mm) were irradiated to a dose of 7 Gy on Theratron (60)Co machine for calibration purpose prior to clinical use. Measurements in each of 34 insertions involving fourteen patients were performed with 5 TLD-100 rods placed along a re-usable rectal marker positioned in the rectum. The dosimeters were read in Harshaw 3500 TLD reader and compared with doses derived from the treatment planning system (TPS) at 1 cm away from the dose prescription points. RESULTS: The mean calculated and measured doses ranged from 2.1-3.8 Gy and 1.2-5.6 Gy with averages of 3.0 +/- 0.5 Gy and 3.1 +/- 1.1 Gy, respectively, for treatment lengths 2-8 cm along the cylinder applicators. The mean values correspond to 48.9% and 50.8% of the prescribed doses, respectively. The deviations of the mean in-vivo doses from the TPS values ranged from -1.9 to 2.1 Gy with a p-value of 0.427. CONCLUSIONS: This study was part of efforts to verify rectal dose obtained from the TPS during vaginal vault brachytherapy. There was no significant difference in the dose to the rectum from the two methods of measurements. PMID- 26816507 TI - Assaying multiple (125)I seeds with the well-ionization chamber SourceCheck(4pi) 33005 and a new insert. AB - PURPOSE: To provide a practical solution that can be adopted in clinical routine to fulfill the AAPM-ESTRO recommendations regarding quality assurance of seeds used in prostate permanent brachytherapy. The aim is to design a new insert for the well-ionization chamber SourceCheck(4pi) 33005 (PTW, Germany) that allows evaluating the mean air-kerma strength of up to ten (125)I seeds with one single measurement instead of measuring each seed individually. MATERIAL AND METHODS: The material required is: a) the SourceCheck(4pi) 33005 well-ionization chamber provided with a PTW insert to measure the air-kerma strength S K of one single seed at a time; b) a newly designed insert that accommodates ten seeds in one column, which allows measuring the mean S K of the ten seeds in one single measurement; and c) a container with ten seeds from the same batch and class of the seeds used for the patient implant, and a set of nine non-radioactive seeds. The new insert is characterized by determining its calibration coefficient, used to convert the reading of the well-chamber when ten seeds are measured to their mean S K . The proposed method is validated by comparing the mean S K of the ten seeds obtained from the new insert with the individual measurement of S K of each seed, evaluated with the PTW insert. RESULTS: The ratio between the calibration coefficient of the new insert and the calibration coefficient of the PTW insert for the SourceCheck(4pi) 33005 is 1.135 +/- 0.007 (k = 1). The mean S K of a set of ten seeds evaluated with this new system is in agreement with the mean value obtained from measuring independently the S K of each seed. CONCLUSIONS: The new insert and procedure allow evaluating the mean S K of ten seeds prior to the implant in a single measurement. The method is faster and more efficient from radiation protection point of view than measuring the individual S K of each seed. PMID- 26816508 TI - Brachytherapy in non melanoma skin cancer of eyelid: a systematic review. AB - PURPOSE: Non melanoma skin cancers (NMSC) of eyelid are uncommon. Many treatments approach are available with surgery being considered as the gold standard. Radiotherapy is an effective alternative in patients unfit for surgery. Brachytherapy (BT) might be a better therapeutic option due high radiation dose concentration to the tumor and rapid dose fall-off resulting in normal tissues sparing. The aim of this review is to evaluate local control, toxicity, and functional cosmetic outcome of BT in NMSC of eyelid. MATERIAL AND METHODS: A systematic search of the bibliographic databases PubMed, Scopus, and Cochrane Library from the earliest possible date through October 2015 was performed. Only studies published in English were included. RESULTS: Six articles fulfilled the selection criteria and were included in our review. Due to high risk of bias, all studies were classified to provide a low level of evidence (according to Scottish Intercollegiate Guidelines Network Classification). No randomized controlled trials or case control studies were founded. Brachytherapy was well tolerated with acceptable toxicity and high local control rates (median: 95.2%). Functional and cosmetic outcome were reported in five study as acceptable good functional cosmetic outcome (median: 100%). CONCLUSIONS: To date, few evidences are available on the role of BT in eyelid NMSC, and they show satisfactory results in terms of local control and functional cosmetic outcome. Therefore, prospective controlled trials are justified. PMID- 26816509 TI - Testicular shielding in penile brachytherapy. AB - PURPOSE: Penile cancer, although rare, is one of the common genitourinary cancers in India affecting mostly aged uncircumcised males. For patients presenting with small superficial lesions < 3 cm restricted to glans, surgery, radical external radiation or brachytherapy may be offered, the latter being preferred as it allows organ and function preservation. In patients receiving brachytherapy, testicular morbidity is not commonly addressed. With an aim to minimize and document the doses to testis after adequate shielding during radical interstitial brachytherapy for penile cancers, we undertook this study in 2 patients undergoing brachytherapy and forms the basis of this report. MATERIAL AND METHODS: Two patients with early stage penile cancer limited to the glans were treated with radical high-dose-rate (HDR) brachytherapy using interstitial implant. A total of 7-8 tubes were implanted in two planes, parallel to the penile shaft. A total dose of 44-48 Gy (55-60 Gy EQD2 doses with alpha/beta = 10) was delivered in 11-12 fractions of 4 Gy each delivered twice daily. Lead sheets adding to 11 mm (4-5 half value layer) were interposed between the penile shaft and scrotum. The testicular dose was measured using thermoluminescent dosimeters. For each patient, dosimetry was done for 3 fractions and mean calculated. RESULTS: The cumulative testicular dose to left and right testis was 31.68 cGy and 42.79 cGy for patient A, and 21.96 cGy and 23.28 cGy for patient B. For the same patients, the mean cumulative dose measured at the posterior aspect of penile shaft was 722.15 cGy and 807.72 cGy, amounting to 16.4% and 16.8% of the prescribed dose. Hence, the application of lead shield 11 mm thick reduced testicular dose from 722-808 cGy to 21.96-42.57 cGy, an "absolute reduction" of 95.99 +/- 1.5%. CONCLUSIONS: With the use of a simple lead shield as described, we were able to effectively reduce testicular dose from "spermicidal" range to "oligospermic" range with possible reversibility. PMID- 26816510 TI - Brachytherapy next generation: robotic systems. AB - In a field dominated by external beam radiation therapy (EBRT), both the therapeutic and technical possibilities of brachytherapy (BT) are underrated, shadowed by protons and intensity modulated radiotherapy. Decreasing expertise and indications, as well as increasing lack of specific BT training for radiation therapy (RT) residents led to the real need of shortening its learning curve and making it more popular. Developing robotic BT devices can be a way to mitigate the above issues. There are many teams working at custom-made robotic BT platforms to perfect and overcome the limitations of the existing systems. This paper provides a picture of the current state-of-the-art in robotic assisted BT, as it also conveys the author's solution to the problem, a parallel robot that uses CT-guidance. PMID- 26816511 TI - Zebra finch males compensate in plumage ornaments at sexual maturation for a bad start in life. AB - BACKGROUND: An individual's fitness in part depends on the characteristics of the mate so that sexually attractive ornaments, as signals of quality, are used in mate choice. Often such ornaments develop already early in life and thus are affected by nutritional conditions experienced then. Individuals thus should benefit by compensating as soon as possible for poor initial development of ornaments, to be attractive already at sexual maturity. Here, we tested whether early nutritional stress affects the cheek patch size of male Zebra finches (Taeniopygia guttata), which are important in mate choice, and whether a small cheek patch size early on is compensated at sexual maturation. Furthermore we tested whether exploration behaviour is affected by such a compensation, as shown for other compensatory growth trajectories. RESULTS: Zebra finch males which were raised under poorer nutritional conditions initially expressed smaller cheek patches at day 50 post-hatching but then compensated in cheek patch size already at 65 days, i.e. when becoming sexually mature. Furthermore, compensatory growth in cheek patch during adolescence was negatively correlated with activity and exploration behaviour, measured in a novel environment. CONCLUSION: This compensation in cheek patch size benefits male attractiveness but also was related to less exploration behaviour, an established proxy for avian personality traits. We discuss the possibility that compensatory priorities exist so that not all deficits from a bad start are caught-up at the same time. Resource allocation to compensate for poorly expressed traits is likely to have evolved to optimise traits by the time they are most beneficial. PMID- 26816512 TI - Stable individual differences in separation calls during early development in cats and mice. AB - BACKGROUND: The development of ethologically meaningful test paradigms in young animals is an essential step in the study of the ontogeny of animal personality. Here we explore the possibility to integrate offspring separation (distress) calls into the study of consistent individual differences in behaviour in two species of mammals, the domestic cat (Felis silvestris catus) and the mound building mouse (Mus spicilegus). Such vocal responses in young mammals are a potentially useful test option as they represent an important element of mother offspring communication with strong implications for offspring survival. In addition, the neural control of vocalisation is closely associated with emotional state. RESULTS: We found marked similarities in the pattern of individual responses of the young of both species to separation from their mother and littermates. In the domestic cat as well as in the mound-building mouse, individual differences in the frequency of calls and to a lesser extent in locomotor activity were repeatable across age, indicating the existence of personality types. Such consistencies across age were also apparent when only considering relative individual differences among litter siblings. In both species, however, individual patterns of vocalisation and locomotor activity were unrelated. This suggests that these two forms of behavioural responses to isolation represent different domains of personality, presumably based on different underlying neurophysiological mechanisms. CONCLUSIONS: Brief separation experiments in young mammals, and particularly the measurement of separation calls, provide a promising approach to study the ontogeny of personality traits. Future long-term studies are needed to investigate the association of these traits with biologically meaningful and potentially repeatable elements of behaviour during later life. PMID- 26816513 TI - The maternal social environment shapes offspring growth, physiology, and behavioural phenotype in guinea pigs. AB - BACKGROUND: Prenatal conditions influence offspring development in many species. In mammals, the effects of social density have traditionally been considered a detrimental form of maternal stress. Now their potential adaptive significance is receiving greater attention.Sex-specific effects of maternal social instability on offspring in guinea pigs (Cavia aperea f. porcellus) have been interpreted as adaptations to high social densities, while the effects of low social density are unknown. Hence, we compared morphological, behavioural and physiological development between offspring born to mothers housed either individually or in groups during the second half of pregnancy. RESULTS: Females housed individually and females housed in groups gave birth to litters of similar size and sex ratios, and there were no differences in birth weight. Sons of individually housed mothers grew faster than their sisters, whereas daughters ofgroup-housed females grew faster than their brothers, primarily due to an effect on growth of daughters. There were few effects on offspring behaviour. Baseline cortisol levels in saliva of pups on day 1 and day 7 were not affected, but we saw a blunted cortisol response to social separation on day 7 in sons of individually housed females and daughters of group-housed females. The effects were consistent across two replicate experiments. CONCLUSIONS: The observed effects only partially support the adaptive hypothesis. Increased growth of daughters may be adaptive under high densities due to increasedfemale competition, but it is unclear why growth of sons is not increased under low social densities when males face less competition from older, dominant males. The differences in growth may be causally linked to sex-specific effects on cortisol response, although individual cortisol response and growth were not correlated, and various other mechanisms are possible. The observed sex-specific effects on early development are intriguing, yet the potential adaptive benefits and physiological mechanisms require further study. PMID- 26816514 TI - Paternal early experiences influence infant development through non-social mechanisms in Rhesus Macaques. AB - BACKGROUND: Early experiences influence the developing organism, with lifelong and potentially adaptive consequences. It has recently become clear that the effects of early experiences are not limited to the exposed generation, but can influence physiological and behavioral traits in the next generation. Mechanisms of transgenerational effects of parental early experiences on offspring development are often attributed to prenatal or postnatal parental influence, but recent data suggest that germ-line plasticity may also play a role in the transgenerational effects of early experiences. These non-genetic transgenerational effects are a potentially important developmental and evolutionary force, but the effects of parental experiences on behavior and physiology are not well understood in socially complex primates. In the non-human primate, the rhesus macaque, nursery rearing (NR) is an early life manipulation used for colony management purposes, and involves separating infants from parents early in life. We examined the effects of maternal and paternal early NR on infant rhesus macaque immunity, physiology, and behavior. RESULTS: We theorized that differences in behavior or physiology in the absence of parent-offspring social contact would point to biological and perhaps germ-line, rather than social, mechanisms of effect. Thus, all subjects were themselves NR. Male and female infant rhesus macaques (N= 206) were separated from parents and social groups in the first four days of life to undergo NR. These infants differed only in their degree of NR ancestry - whether their dams or sires were themselves NR. At 3-4 months of age, infants underwent a standardized biobehavioral assessment. Factors describing immunity, plasma cortisol, and emotion regulation were generated from these data using factor analysis. Paternal, but not maternal, NR was associated with greater emotionality and higher plasma cortisol, compared with infants born to CONTROL reared fathers. CONCLUSIONS: These data suggest that macaque biobehavioral makeup is strongly influenced by paternal experiences, and via non-social mechanisms. PMID- 26816515 TI - Eco-evo-devo of the lemur syndrome: did adaptive behavioral plasticity get canalized in a large primate radiation? AB - BACKGROUND: Comprehensive explanations of behavioral adaptations rarely invoke all levels famously admonished by Niko Tinbergen. The role of developmental processes and plasticity, in particular, has often been neglected. In this paper, we combine ecological, physiological and developmental perspectives in developing a hypothesis to account for the evolution of 'the lemur syndrome', a combination of reduced sexual dimorphism, even adult sex ratios, female dominance and mild genital masculinization characterizing group-living species in two families of Malagasy primates. RESULTS: We review the different components of the lemur syndrome and compare it with similar adaptations reported for other mammals. We find support for the assertion that the lemur syndrome represents a unique set of integrated behavioral, demographic and morphological traits. We combine existing hypotheses about underlying adaptive function and proximate causation by adding a potential developmental mechanism linking maternal stress and filial masculinization, and outline an evolutionary scenario for its canalization. CONCLUSIONS: We propose a new hypothesis linking ecological, physiological, developmental and evolutionary processes to adumbrate a comprehensive explanation for the evolution of the lemur syndrome, whose assumptions and predictions can guide diverse future research on lemurs. This hypothesis should also encourage students of other behavioral phenomena to consider the potential role of developmental plasticity in evolutionary innovation. PMID- 26816516 TI - Lifetime development of behavioural phenotype in the house mouse (Mus musculus). AB - With each trajectory taken during the ontogeny of an individual, the number of optional behavioural phenotypes that can be expressed across its life span is reduced. The initial range of phenotypic plasticity is largely determined by the genetic material/composition of the gametes whereas interacting with the given environment shapes individuals to adapt to/cope with specific demands. In mammalian species, the phenotype is shaped as the foetus grows, depending on the environment in the uterus, which in turn depends on the outer environment the mother experiences during pregnancy. After birth, a complex interaction between innate constitution and environmental conditions shapes individual lifetime trajectories, bringing about a wide range of diversity among individual subjects. In laboratory mice inbreeding has been systematically induced in order to reduce the genetic variability between experimental subjects. In addition, within most laboratories conducting behavioural phenotyping with mice, breeding and housing conditions are highly standardised. Despite such standardisation efforts a considerable amount of variability persists in the behaviour of mice. There is good evidence that phenotypic variation is not merely random but might involve individual specific behavioural patterns consistent over time. In order to understand the mechanisms and the possible adaptive value of the maintenance of individuality we review the emergence of behavioural phenotypes over the course of the life of (laboratory) mice. We present a literature review summarizing developmental stages of behavioural development of mice along with three illustrative case studies. We conclude that the accumulation of environmental differences and experiences lead to a "mouse individuality" that becomes increasingly stable over the lifetime. PMID- 26816517 TI - Stability and change: Stress responses and the shaping of behavioral phenotypes over the life span. AB - In mammals, maternal signals conveyed via influences on hypothalamic-pituitary adrenal (HPA) activity may shape behavior of the young to be better adapted for prevailing environmental conditions. However, the mother's influence extends beyond classic stress response systems. In guinea pigs, several hours (h) of separation from the mother activates not only the HPA axis, but also the innate immune system, which effects immediate behavioral change, as well as modifies behavioral responsiveness in the future. Moreover, the presence of the mother potently suppresses the behavioral consequences of this innate immune activation. These findings raise the possibility that long-term adaptive behavioral change can be mediated by the mother's influence on immune-related activity of her pups. Furthermore, the impact of social partners on physiological stress responses and their behavioral outcomes are not limited to the infantile period. A particularly crucial period for social development in male guinea pigs is that surrounding the attainment of sexual maturation. At this time, social interactions with adults can dramatically affect circulating cortisol concentrations and social behavior in ways that appear to prepare the male to best cope in its likely future social environment. Despite such multiple social influences on the behavior of guinea pigs at different ages, inter-individual differences in the magnitude of the cortisol response remain surprisingly stable over most of the life span. Together, it appears that throughout the life span, physiological stress responses may be regulated by social stimuli. These influences are hypothesized to adjust behavior for predicted environmental conditions. In addition, stable individual differences might provide a means of facilitating adaptation to less predictable conditions. PMID- 26816518 TI - The importance of genotype-by-age interactions for the development of repeatable behavior and correlated behaviors over lifetime. AB - Behaviors are highly plastic and one aspect of this plasticity is behavioral changes over age. The presence of age-related plasticity in behavior opens up the possibility of between-individual variation in age-related plasticity (Individual Age interaction, IxA) and genotype-age interaction (GxA). We outline the available approaches for quantifying GxA. We underline that knowledge of GxA for behaviors is an important step in reaching and understanding of the evolution of plasticity in behavior over lifetime. In particular, the heritability (repeatability) and/or the rank order of behavior across individuals are predicted to change across ages in presence of GxA. We draw on the theory of reaction norms to illustrate that GxA, when present, is likely to lead to developmental changes in the magnitude and possibly sign of the genetic correlation between behaviors (behavioral syndrome). We present an overview of the literature on changes in the ranking of individuals' behavior across ages, and in the correlation between behaviors. Although all studies were carried out on the phenotypic level, they overall suggest clear scope for increased study of GxA as a process explaining age-related plasticity in behaviors. Lastly, we throughout emphasize that many of the approaches and underlying theory of GxA is applicable to the study of IxA, which is informative as it presents the upper limit of GxA, but is also a more attainable target of study in many systems. Empirical work aimed at understanding IxA and GxA in behavior is needed in order to understand whether patterns predicted by theory on plasticity indeed occur for age-related plasticity of behavior. PMID- 26816519 TI - The Snark was a Boojum - reloaded. AB - In this article, we refer to an original opinion paper written by Prof. Frank Beach in 1950 ("The Snark was a Boojum"). In his manuscript, Beach explicitly criticised the field of comparative psychology because of the disparity between the original understanding of comparativeness and its practical overly specialised implementation. Specialisation encompassed both experimental species (rats accounted for 70% of all subjects) and test paradigms (dominated by conditioning/learning experiments). Herein, we attempt to evaluate the extent to which these considerations apply to current behavioural neuroscience. Such evaluation is particularly interesting in the context of "translational research" that has recently gained growing attention. As a community, we believe that preclinical findings are intended to inform clinical practice at the level of therapies and knowledge advancements. Yet, limited reproducibility of experimental results and failures to translate preclinical research into clinical trial sindicate that these expectations are not entirely fulfilled. Theoretical considerations suggest that, before concluding that a given phenomenon is of relevance to our species, it should be observed in more than a single experimental model (be it an animal strain or species) and tested in more than a single standardized test battery. Yet, current approaches appear limited in terms of variability and overspecialised in terms of operative procedures. Specifically, as in 1950, rodents (mice instead of rats) still constitute the vast majority of animal species investigated. Additionally, the scientific community strives to homogenise experimental test strategies, thereby not only limiting the generalizability of the findings, but also working against the design of innovative approaches. Finally, we discuss the importance of evolutionary-adaptive considerations within the field of laboratory research. Specifically, resting upon empirical evidence indicating that developing individuals adjust their long-term phenotype according to early environmental demands, we propose that current rearing and housing standards do not adequately prepare experimental subjects to their actual adult environments. Specifically, while the adult life of a laboratory animal is characterized by frequent stimulations and challenges, the neonatal life is dominated by quietness and stability. We suggest that such form of mismatch may remarkably influence the reproducibility and reliability of experimental findings. PMID- 26816520 TI - Hazards inherent in interdisciplinary behavioral research. AB - Many, if not all, questions in biology and psychology today were formulated and considered in depth, though typically in a different language, from the 1700's to the early 1900's. However, because of politics or fashion, some topics fell out of favor or failed to recruit new scientists and hence languished. Despite greatly expanded scholarship in the history of the life sciences in the twentieth century, many such topics have had to be rediscovered in recent years, while much of the wisdom already accrued stays in the older literature and not in active minds. This is particularly true today when scientific advances appear at breakneck speed. It would not be an exaggeration to say that many 'breakthroughs' turn out really to be rediscoveries of forgotten observations. Two areas of particular significance to the interdisciplinary study of behavior are the Norms of Reaction (from Biology) and the concept of Plasticity (from Psychology). These and related fields benefit from the perspective of epigenetics so long as rigorous operational definitions are implemented. It is also important to revive Hogben's admonition that the interaction of hereditary and environment cannot be understood outside of the context of development. Five examples of increasing complexity in phenotypic plasticity in brain and behavior are presented to illustrate this perspective. PMID- 26816521 TI - Adaptive explanations for sensitive windows in development. AB - Development in many organisms appears to show evidence of sensitive windows periods or stages in ontogeny in which individual experience has a particularly strong influence on the phenotype (compared to other periods or stages). Despite great interest in sensitive windows from both fundamental and applied perspectives, the functional (adaptive) reasons why they have evolved are unclear. Here we outline a conceptual framework for understanding when natural selection should favour changes in plasticity across development. Our approach builds on previous theory on the evolution of phenotypic plasticity, which relates individual and population differences in plasticity to two factors: the degree of uncertainty about the environmental conditions and the extent to which experiences during development ('cues') provide information about those conditions. We argue that systematic variation in these two factors often occurs within the lifetime of a single individual, which will select for developmental changes in plasticity. Of central importance is how informational properties of the environment interact with the life history of the organism. Phenotypes may be more or less sensitive to environmental cues at different points in development because of systematic changes in (i) the frequency of cues, (ii) the informativeness of cues, (iii) the fitness benefits of information and/or (iv) the constraints on plasticity. In relatively stable environments, a sensible null expectation is that plasticity will gradually decline with age as the developing individual gathers information. We review recent models on the evolution of developmental changes in plasticity and explain how they fit into our conceptual framework. Our aim is to encourage an adaptive perspective on sensitive windows in development. PMID- 26816522 TI - Plasticity as a developing trait: exploring the implications. AB - Individual differences in plasticity have been classically framed as genotype-by environment interactions, with different genotypes showing different reaction norms in response to environmental conditions. However, research has shown that early experience can be a critical factor in shaping an individual's plasticity to later environmental factors. In other words, plasticity itself can be investigated as a developing trait that reflects the combined action of an individual's genes and previous interactions with the environment. In this paper I explore some implications of the idea that the early environment modulates long term plasticity, with an emphasis on plasticity in behavioral traits. I begin by focusing on the mechanisms that mediate plasticity at the proximate level, and discussing the possibility that some traits may work as generalized mediators of plasticity by affecting the sensitivity of multiple phenol types across developmental contexts. I then tackle the complex problem of the evolution of reaction norms for plasticity. Next, I consider a number of potential implications for research on parental effects and phenotypic matching, and conclude by discussing how plasticity may become a target of evolutionary conflict between parents and offspring. In total, I aim to show how the idea of plasticity as a developing trait offers a rich source of questions and insights that may inform future research in this area. PMID- 26816523 TI - Introducing biological realism into the study of developmental plasticity in behaviour. AB - There is increasing attention for integrating mechanistic and functional approaches to the study of (behavioural) development. As environments are mostly unstable, it is now often assumed that genetic parental information is in many cases not sufficient for offspring to become optimally adapted to the environment and that early environmental cues, either indirectly via the parents or from direct experience, are necessary to prepare them for a specific environment later in life. To study whether these early developmental processes are adaptive and through which mechanism, not only the early environmental cues but also how they impinge on the later-life environmental context has therefore to be taken into account when measuring the animal's performance. We first discuss at the conceptual level six ways in which interactions between influences of different time windows during development may act (consolidation, cumulative information gathering and priming, compensation, buffering, matching and mismatching, context dependent trait expression). In addition we discuss how different environmental factors during the same time window may interact in shaping the phenotype during development. Next we discuss the pros and cons of several experimental designs for testing these interaction effects, highlighting the necessity for full, reciprocal designs and the importance of adjusting the nature and time of manipulation to the animal's adaptive capacity. We then review support for the interaction effects from both theoretical models and animal experiments in different taxa. This demonstrates indeed the existence of interactions at multiple levels, including different environmental factors, different time windows and between generations. As a consequence, development is a life-long, environment-dependent process and therefore manipulating only the early environment without taking interaction effects with other and later environmental influences into account may lead to wrong conclusions and may also explain inconsistent results in the literature. PMID- 26816525 TI - Behavioural phenotypes over the lifetime of a holometabolous insect. AB - INTRODUCTION: Behavioural traits can differ considerably between individuals, and such differences were found to be consistent over the lifetime of an organism in several species. Whether behavioural traits of holometabolous insects, which undergo a metamorphosis, are consistent across ontogeny is virtually unexplored. We investigated several behavioural parameters at five different time points in the lifetime of the holometabolous mustard leaf beetle Phaedon cochleariae (Coleoptera: Chrysomelidae), two times in the larval (second and third larval stage) and three times in the adult stage. We investigated 1) the stability of the behavioural phenotype (population level), 2) whether individuals rank consistently across behavioural traits and over their lifetime (individual level), and 3) in how far behavioural traits are correlated with the developmental time of the individuals. RESULTS: We identified two behavioural dimensions in every life stage of P. cochleariae, activity and boldness (population level). Larvae and young adults ranked consistently across the investigated behavioural traits, whereas consistency over time was only found in adults but not between larvae and adults (individual level). Compared to adult beetles, larvae were less active. Moreover, younger larvae were bolder than all subsequent life stages. Over the adult lifetime of the beetles, males were less active than females. Furthermore, the activity of second instar larvae was significantly negatively correlated with the development time. CONCLUSIONS: Our study highlights that, although there is no individual consistency over the larval and the adult life stage, the behavioural clustering shows similar patterns at all tested life stages of a holometabolous insect. Nevertheless, age- and sex-specific differences in behavioural traits occur which may be explained by different challenges an individual faces at each life stage. These differences are presumably related to the tremendous changes in life-history traits from larvae to adults and/or to a niche shift after metamorphosis as well as to different needs of both sexes, respectively. A faster development of more active compared to less active second instar larvae is in line with the pace-of-life syndrome. Overall, this study demonstrates a pronounced individuality in behavioural phenotypes and presumably adaptive changes related to life stage and sex. PMID- 26816524 TI - Endocrine mechanisms, behavioral phenotypes and plasticity: known relationships and open questions. AB - Behavior of wild vertebrate individuals can vary in response to environmental or social factors. Such within-individual behavioral variation is often mediated by hormonal mechanisms. Hormones also serve as a basis for among-individual variations in behavior including animal personalities and the degree of responsiveness to environmental and social stimuli. How do relationships between hormones and behavioral traits evolve to produce such behavioral diversity within and among individuals? Answering questions about evolutionary processes generating among-individual variation requires characterizing how specific hormones are related to variation in specific behavioral traits, whether observed hormonal variation is related to individual fitness and, whether hormonal traits are consistent (repeatable) aspects of an individual's phenotype. With respect to within-individual variation, we need to improve our insight into the nature of the quantitative relationships between hormones and the traits they regulate, which in turn will determine how they may mediate behavioral plasticity of individuals. To address these questions, we review the actions of two steroid hormones, corticosterone and testosterone, in mediating changes in vertebrate behavior, focusing primarily on birds. In the first part, we concentrate on among individual variation and present examples for how variation in corticosterone concentrations can relate to behaviors such as exploration of novel environments and parental care. We then review studies on correlations between corticosterone variation and fitness, and on the repeatability over time of corticosterone concentrations. At the end of this section, we suggest that further progress in our understanding of evolutionary patterns in the hormonal regulation of behavior may require, as one major tool, reaction norm approaches to characterize hormonal phenotypes as well as their responses to environments. In the second part, we discuss types of quantitative relationships between hormones and behavioral traits within individuals, using testosterone as an example. We review conceptual models for testosterone-behavior relationships and discuss the relevance of these models for within-individual plasticity in behavior. Next, we discuss approaches for testing the nature of quantitative relationships between testosterone and behavior, concluding that again reaction norm approaches might be a fruitful way forward. We propose that an integration of new tools, especially of reaction norm approaches into the field of behavioral endocrinology will allow us to make significant progress in our understanding of the mechanisms, the functional implications and the evolution of hormone-behavior relationships that mediate variation both within and among individuals. This knowledge will be crucial in light of already ongoing habitat alterations due to global change, as it will allow us to evaluate the mechanisms as well as the capacity of wild populations to adjust hormonally-mediated behaviors to altered environmental conditions. PMID- 26816526 TI - Association between increased blood interleukin-6 levels on emergency department arrival and prolonged length of intensive care unit stay for blunt trauma. AB - BACKGROUND: Systemic immune response to injury plays a key role in the pathophysiological mechanism of blunt trauma. We tested the hypothesis that increased blood interleukin-6 (IL-6) levels of blunt trauma patients on emergency department (ED) arrival are associated with poor clinical outcomes, and investigated the utility of rapid measurement of the blood IL-6 level. METHODS: We enrolled 208 consecutive trauma patients who were transferred from the scene of an accident to a level I trauma centre in Japan and admitted to the intensive care unit (ICU). Blood IL-6 levels on ED arrival were measured by using a rapid measurement assay. The primary outcome variable was prolonged ICU stay (length of ICU stay > 7 days). The secondary outcomes were 28-day mortality, probability of survival and Abbreviated Injury Scale (AIS) scores. RESULTS: Patients with prolonged ICU stay had significantly higher blood IL-6 levels on ED arrival than the patients without prolonged ICU stay (P < 0.0001). The receiver-operating characteristic curves produced an area under the curve of 0.75 (95 % confidence interval [CI], 0.66-0.84; P < 0.0001) for prolonged ICU stay. The patients who had increased blood IL-6 levels on ED arrival had increased 28-day mortality (P = 0.021) and decreased probability of survival (P < 0.0001). The AIS scores for the thorax, abdomen, extremity, and external body regions independently correlated with blood IL-6 levels (unstandardized coefficients [95 % CI] for the thorax: 23.8 [12.6-35.1]; P < 0.0001; abdomen: 42.7 [23.8-61.7]; P < 0.0001; extremity: 19.0 [5.5-32.4]; P = 0.0060; external body regions: 62.9 [13.2-112.7]; P = 0.030); the standardized coefficients for the thorax (0.27) and abdomen (0.28) were larger than those for the extremity (0.18) and external body regions (0.15). CONCLUSIONS: Increased blood IL-6 level on ED arrival was significantly associated with prolonged length of ICU stay. Blood IL-6 level on ED arrival independently correlated with the AIS scores for the abdomen and thorax, and, to a lesser extent, those for the extremity and external body regions. The rapid measurement of blood IL-6 level on ED arrival can be utilized as a fast screening tool to improve assessment of injury severity and prediction of clinical outcomes in the initial phase of trauma care. PMID- 26816527 TI - Prevalence of human papillomavirus genotypes among women with cervical cancer in Ghana. AB - BACKGROUND: Human Papillomavirus (HPV) infections have been shown to be a necessary risk factor for the development of cervical cancer. However, HPV genotype distribution varies geographically, both in type and relative prevalence. In order to ensure a successful introduction of available vaccines, there is the need to identify pre-vaccination HPV genotype prevalence in Ghana and the extent of single and multiple-infections. METHODS: Paraffin-embedded cervical tissues of 256 confirmed cervical cancer cases diagnosed at the Korle-Bu Teaching Hospital during the period January 2004 to December 2006 were selected after hematoxylin and eosin staining and confirmation. Following a heat proteinase K-based tissue lysis, HPV was detected and typed by a nested-multiplex PCR assay using an E6/E7 consensus primer and type-specific primers. RESULTS: Of the 256 cases, 230 (89.8 %, 95 % CI 85.7-93.4 %) were positive for HPV DNA. HPV18 (47.4 %), HPV59 (42.2 %), HPV45 (37.4 %) and HPV16 (9.0 %) were the four common HPV genotypes detected. A total of 110 (47.8 %) of the 230 HPV DNA positive tissues, were infected by a single HPV genotype while the other 120 (52.2 %) were infected by multiple HPV genotypes. A significant association was determined between each of the following HPV genotypes and multiple-infection; HPV18 (OR = 6.97; 95 % CI, 3.89-12.50), HPV59 (OR = 9.56; 95 % CI, 5.57-20.02) and HPV45 (OR = 1.94; 95 % CI, 1.12-3.35). CONCLUSION: The prevalence of the following high risk HPV genotypes (HPV18, HPV59, HPV45) were relatively high among the cases of cervical cancers reported at this hospital in Ghana during the study period. Additionally, there was a high frequency of HPV multiple-infections among these cases. PMID- 26816528 TI - Rate-constraining changes in surface properties, porosity and hydrolysis kinetics of lignocellulose in the course of enzymatic saccharification. AB - BACKGROUND: Explaining the reduction of hydrolysis rate during lignocellulose hydrolysis is a challenge for the understanding and modelling of the process. This article reports the changes of cellulose and lignin surface areas, porosity and the residual cellulase activity during the hydrolysis of autohydrolysed wheat straw and delignified wheat straw. The potential rate-constraining mechanisms are assessed with a simplified kinetic model and compared to the observed effects, residual cellulase activity and product inhibition. RESULTS: The reaction rate depended exclusively on the degree of hydrolysis, while enzyme denaturation or time-dependent changes in substrate hydrolysability were absent. Cellulose surface area decreased linearly with hydrolysis, in correlation with total cellulose content. Lignin surface area was initially decreased by the dissolution of phenolics and then remained unchanged. The dissolved phenolics did not contribute to product inhibition. The porosity of delignified straw was decreased during hydrolysis, but no difference in porosity was detected during the hydrolysis of autohydrolysed straw. CONCLUSIONS: Although a hydrolysis-dependent increase of non-productive binding capacity of lignin was not apparent, the dependence of hydrolysis maxima on the enzyme dosage was best explained by partial irreversible product inhibition. Cellulose surface area correlated with the total cellulose content, which is thus an appropriate approximation of the substrate concentration for kinetic modelling. Kinetic models of cellulose hydrolysis should be simplified enough to include reversible and irreversible product inhibition and reduction of hydrolysability, as well as their possible non-linear relations to hydrolysis degree, without overparameterization of particular factors. PMID- 26816529 TI - Acceleration of biodetoxification on dilute acid pretreated lignocellulose feedstock by aeration and the consequent ethanol fermentation evaluation. AB - BACKGROUND: Biodetoxification by the fungus Amorphotheca resinae ZN1 provides an effective way of inhibitor removal from pretreated lignocellulose feedstock and has been applied in the process of ethanol, biolipids, and lactic acid production. However, the long-time used and the consumption of considerable xylose in the pretreated materials reduced the process efficiency. The improvements of biodetoxification should be made to enhance the production of biochemical from lignocellulosic materials. RESULTS: This study reported an acceleration method of A. resinae ZN1-based biodetoxification on the corn stover (CS) feedstock pretreated using dry dilute acid pretreatment. Under proper aeration and well-mixing condition, the conversion rate of furfural, 5 hydroxymethylfurfural (HMF), acetic acid, and typical phenolic compounds were significantly accelerated by more than twofolds faster, which resulted in the reduction of biodetoxification time from 96 h in the conventional process to 36 h. Simultaneous saccharification and ethanol fermentation assay on accelerated biodetoxification of the dry dilute acid pretreated CS feedstock achieved the similar ethanol titer (48.56 g/L of 36 h' accelerated biodetoxification vs. 50.00 g/L of 4 days' conventional biodetoxification) and yield (58.10 vs. 59.63 %). Substrate priority of inhibitors to sugars by A. resinae ZN1 was discovered and considerable xylose was reserved in the accelerated biodetoxification. Cell growth of A. resinae fungus in liquid medium and on pretreated CS solids revealed that the enhanced aeration enhanced the biodetoxification rate rather than the cell growth rate. Accelerated inhibitor conversion might come from the increased supply of cofactors of nicotinamide adenine dinucleotide or nicotinamide adenine dinucleotide phosphate from the step of aldehyde inhibitors to the corresponding acids, instead of cell mass increase. CONCLUSION: Accelerated biodetoxification reduced the period of biodetoxification and retained the xylose components in the pretreated CS, which provided a practical method on improving process efficiency for cellulosic ethanol production from severe pretreated lignocellulose feedstock. PMID- 26816530 TI - Effects of lignin and surfactant on adsorption and hydrolysis of cellulases on cellulose. AB - BACKGROUND: Considerable works have been reported concerning the obstruction of enzymatic hydrolysis efficiency by lignin. However, there is a lack of information about the influence of lignin on the adsorption of cellulases on cellulose, along with the hydrolytic activity of the cellulases adsorbed on lignin. In addition, limited discovery has been reported about the influence of additives on cellulase desorption from lignin and lignocellulosic materials. In this work, the effects of lignin on cellulase adsorption and hydrolysis of Avicel were investigated and the effects of Tween 80 on cellulases adsorption and desorption on/from lignin and corn stover were explored. RESULTS: The results showed that the maximum adsorption capacity of Avicel reduced from 276.9 to 179.7 and 112.1 mg/g cellulose with the addition of 1 and 10 mg lignin per gram Avicel, which indicated that lignin adsorbed on Avicel reduced surface area of cellulose and lignin available for cellulases. Cellulases adsorbed on lignin could be released by reaching new adsorption equilibrium between lignin and supernatants. In addition, cellulases desorbed from lignin still possess hydrolytic capacity. Tween 80 could adsorb onto both lignin and corn stover, and reduce the cellulase adsorption on them. Furthermore, Tween 80 could enhance desorption of cellulases from both lignin and corn stover, which might be due to the competitive adsorption between cellulases and Tween 80 on them. CONCLUSIONS: The presence of lignin decreased the maximum adsorption capacity of cellulases on cellulose and the cellulases adsorbed on lignin could be released to supernatant, exhibiting hydrolytic activity. Tween 80 could alleviate the adsorption of cellulases and enhanced desorption of cellulases on/from lignin and corn stover. The conclusions of this work help us further understanding the role of lignin in the reduction of adsorption of cellulases on substrates, and the function of additives in cellulases adsorption and desorption on/from lignin and substrates. PMID- 26816531 TI - The relationship of foot and ankle mobility to the frontal plane projection angle in asymptomatic adults. AB - BACKGROUND: The frontal plane projection angle (FPPA) is frequently used as a measure of dynamic knee valgus during functional tasks, such as the single leg squat. Increased dynamic knee valgus is observed in people with knee pathologies including patellofemoral pain and anterior cruciate injury. As the foot is the primary interface with the support surface, foot and ankle mobility may affect the FPPA. This study investigated the relationship between foot and ankle mobility and the FPPA in asymptomatic adults. METHODS: Thirty healthy people (aged 18-50 years) performed 5 single leg squats. Peak FPPA and FPPA excursion were determined from digital video recordings. Foot mobility was quantified as the difference in dorsal midfoot height or midfoot width, between non weightbearing and bilateral weightbearing positions. Ankle joint dorsiflexion range was measured as the maximum distance in centimetres between the longest toe and the wall during a knee-to-wall lunge. Linear regressions with generalised estimating equations were used to examine relationships between variables. RESULTS: Higher midfoot width mobility was associated with greater peak FPPA (beta 0.90, p < 0.001, odds ratio [OR] 2.5), and FPPA excursion (beta 0.67, p < 0.001, OR 1.9). Lower midfoot height mobility was associated with greater peak FPPA (beta 0.37, p = 0.030, OR 1.4) and FPPA excursion (beta 0.30, p = 0.020, OR 1.3). Lower ankle joint dorsiflexion was also associated with greater peak FPPA (beta 0.61, p = 0.008, OR 1.8) and greater FPPA excursion (beta 0.56, p < 0.001, OR 1.7). CONCLUSIONS: Foot and ankle mobility was significantly related to the FPPA during the single leg squat in healthy individuals. Specifically, higher midfoot width mobility, or lower ankle joint dorsiflexion range and midfoot height mobility, were associated with a greater FPPA. These foot mobility factors should be considered in the clinical management of knee-related disorders that are associated with a high FPPA. PMID- 26816532 TI - How frequently do clusters occur in hierarchical clustering analysis? A graph theoretical approach to studying ties in proximity. AB - BACKGROUND: Hierarchical cluster analysis (HCA) is a widely used classificatory technique in many areas of scientific knowledge. Applications usually yield a dendrogram from an HCA run over a given data set, using a grouping algorithm and a similarity measure. However, even when such parameters are fixed, ties in proximity (i.e. two equidistant clusters from a third one) may produce several different dendrograms, having different possible clustering patterns (different classifications). This situation is usually disregarded and conclusions are based on a single result, leading to questions concerning the permanence of clusters in all the resulting dendrograms; this happens, for example, when using HCA for grouping molecular descriptors to select that less similar ones in QSAR studies. RESULTS: Representing dendrograms in graph theoretical terms allowed us to introduce four measures of cluster frequency in a canonical way, and use them to calculate cluster frequencies over the set of all possible dendrograms, taking all ties in proximity into account. A toy example of well separated clusters was used, as well as a set of 1666 molecular descriptors calculated for a group of molecules having hepatotoxic activity to show how our functions may be used for studying the effect of ties in HCA analysis. Such functions were not restricted to the tie case; the possibility of using them to derive cluster stability measurements on arbitrary sets of dendrograms having the same leaves is discussed, e.g. dendrograms from variations of HCA parameters. It was found that ties occurred frequently, some yielding tens of thousands of dendrograms, even for small data sets. CONCLUSIONS: Our approach was able to detect trends in clustering patterns by offering a simple way of measuring their frequency, which is often very low. This would imply, that inferences and models based on descriptor classifications (e.g. QSAR) are likely to be biased, thereby requiring an assessment of their reliability. Moreover, any classification of molecular descriptors is likely to be far from unique. Our results highlight the need for evaluating the effect of ties on clustering patterns before classification results can be used accurately.Graphical abstractFour cluster contrast functions identifying statistically sound clusters within dendrograms considering ties in proximity. PMID- 26816533 TI - Crizotinib versus platinum-based double-agent chemotherapy as the first line treatment in advanced anaplastic lymphoma kinase-positive lung adenocarcinoma. AB - BACKGROUND: To explore the efficacy and safety of crizotinib versus platinum based double agent chemotherapy as the first-line treatment in patients with advanced anaplastic lymphoma kinase (ALK)-positive lung adenocarcinoma. METHOD: We retrospectively analyzed data from 19 patients with advanced ALK-positive lung adenocarcinoma who had received no previous systemic treatment for advanced disease. Seven patients received oral crizotinib at a dose of 250 mg twice daily; 12 patients were administered standard chemotherapy (pemetrexed, paclitaxel, vinorelbine or gemcitabine plus either cisplatin or carboplatin) every three weeks for up to six cycles. The primary endpoint was overall response rate (ORR), disease control rate (DCR), and safety. RESULTS: The ORR was significantly higher with crizotinib than with chemotherapy (83.3% in the crizotinib vs. 25.0% in the chemotherapy group, P < 0.05); the DCRs were 100% and 75%, respectively (P < 0.05). The common adverse events associated with crizotinib were visual abnormality and diarrhea, whereas those associated with chemotherapy were neutropenia and nausea. In the crizotinib group, liver aminotransferase elevation (adverse events grade 3 or 4) occurred in one patient (14.3%). In the chemotherapy group, the same grade neutropenia adverse event occurred in two patients (16.6%). The incidence of treatment-related grade 3 or 4 adverse events was similar in both groups. Compared with chemotherapy, crizotinib was associated with a greater reduction in lung cancer symptoms and a greater improvement in quality of life. CONCLUSION: As a first-line treatment, crizotinib was superior to platinum-based double chemotherapy in patients with previously untreated advanced ALK-positive lung adenocarcinoma. Therefore, crizotinib is an optimal therapy as a first-line treatment in these patients. PMID- 26816534 TI - Transcriptional factor FOXO3 negatively regulates the expression of nm23-H1 in non-small cell lung cancer. AB - BACKGROUND: Nm23-H1 was the first metastasis suppressor discovered in most tumor models and reduction or loss of nm23-H1 expression correlates with tumor progression and metastasis in non-small-cell lung cancer. Despite extensive studies, the regulatory mechanism of nm23-H1 expression is far from elucidated. The transcriptional factor forkhead box (FOX)O3 has been reported to be involved in multiple regulatory signaling pathways in the biological behavior of tumors. Therefore, we aimed to study the relationship between FOXO3 activity and nm23-H1 expression. METHODS: Real time reverse transcriptase-polymerase chain reaction and Western blotting assays were employed to determine nm23-H1 messenger ribonucleic acid and protein expression after being transformed by different FOXO3 plasmid in A549 cells. A dual luciferase reporter system and chromatin immunoprecipitation assay, were used to determine the promoter activity of the nm23-H1 gene and to detect the binding of FOXO3 into the nm23-H1 promoter, respectively. RESULTS: We found that activated FOXO3 decreased nm23-H1 expression and dominant negative FOXO3 increased nm23-H1 expression. Modulation of FOXO3 activity with FOXO3 pathway inhibitors altered nm23-H1 promoter activity. Although there is a putative binding site of FOXO3 in the nm23-H1 promoter, FOXO3 regulated nm23-H1 expression in an indirect manner. CONCLUSION: We demonstrated that the transcriptional factor FOXO3 decreased the expression levels of the tumor suppressor gene nm23-H1 in the non-small-cell lung cancer A549 cell line and that the level of expression of nm23-H1 was controlled by FOXO3 in an indirect manner. This finding provided an insight into the upstream regulation of nm23-H1 and may provide promising targets for inhibition of the metastasis process. PMID- 26816535 TI - Identification of lung adenocarcinoma mutation status based on histologic subtype: Retrospective analysis of 269 patients. AB - BACKGROUND: To evaluate differences in the clinical characteristics and molecular pathology of lung adenocarcinoma subtypes as defined by the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international histological classification. METHODS: We retrospectively reviewed 269 patients with initial primary lung adenocarcinoma who had undergone complete resection at our department from August 2013 to December 2014, focusing on the new histologic subtype classification, clinical characteristics, and molecular pathology. RESULTS: All specimens were invasive adenocarcinoma, and were lepidic (13.0%), papillary (19.7%), acinar (51.7%), solid (8.6%), micropapillary (1.1%) or mucinous predominant (5.9%). Epidermal growth factor receptor (EGFR) mutations were detected in 132 cases (60.3%). Female patients and non-smokers had higher EGFR mutation rates (P = 0.022 and 0.026, respectively). The lepidic, papillary, acinar, solid, micropapillary, and mucinous predominant patterns had EGFR mutation rates of 70.6%, 64.8%, 72.5%, 33.3%, 100%, and 5.9%, respectively. The exon mutation distribution differed according to serum carcinoembryonic antigen (CEA) levels (P = 0.018). v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were detected in 20 cases (9.2%), and were frequently found in the mucinous and solid predominant subtypes. The serum CEA levels differed among the subtypes. CONCLUSIONS: In China, there are significant differences between lung adenocarcinoma histologic subtypes. The presence of well-differentiated components in lung adenocarcinoma indicates higher EGFR mutation rates; the presence of solid or mucinous components indicates higher KRAS mutation rates. Serum CEA levels are associated with histologic subtype and EGFR exon mutations. PMID- 26816536 TI - CUG-binding protein 1 (CUGBP1) expression and prognosis of brain metastases from non-small cell lung cancer. AB - BACKGROUND: The brain is a frequent site of metastases from non-small cell lung cancer (NSCLC). The purpose of this study was to detect the expression of CUG binding protein 1 (CUGBP1) messenger ribonucleic acid (mRNA) and Ki-67 in metastasized brain tissue from NSCLC and determine the relationship between CUGBP1 and brain metastases. METHODS: The expression of CUGBP1 mRNA and Ki-67 in metastasized brain tissue from NSCLC was investigated by semiquantitative polymerase chain reaction and immunohistochemistry, respectively. The expression of CUGBP1 and Ki-67 in metastasized brain tissue from NSCLC was related to clinical characteristics, as assessed using the chi-square test. The prognostic significance was assessed by univariate and multivariate analyses using the Cox hazard model. RESULTS: The expression of CUGBP1 mRNA and Ki-67 was overexpressed in metastasized brain tissue from NSCLC and was correlated with differentiation. In addition, by both univariate and multivariate survival analyses, CUGBP1 expression, Ki-67 expression, and age were noted to be independent indicators of a shorter postsurgical survival. CONCLUSION: The expression of CUGBP1 is an important factor in the development of brain metastases from NSCLC. PMID- 26816537 TI - Retrospective analysis of unknown primary cancers with malignant pleural effusion at initial diagnosis. AB - BACKGROUND: Malignant pleural effusion (MPE) can occur during the progression of various cancers. However, factors, such as the incidence of MPE associated with different types of cancers and its potential for diagnosing previously undetected cancers, are unknown. Moreover, MPE may accompany potentially curable cancers or those with a favorable survival prognosis with adequate treatment. The present study determined the types of cancers accompanied by MPE at initial diagnosis and investigated appropriate related methods for diagnosing previously unknown cancers. METHODS: We retrospectively reviewed the medical records of 35 patients with MPE at initial cancer diagnosis between 2004 and 2012. We evaluated the patient characteristics, final diagnosis, and diagnostic processes. RESULTS: Of the 35 patients, 10 had lung cancer, seven ovarian or peritoneal cancer, four malignant pleural mesothelioma, one breast cancer, one lymphoma, one pancreatic cancer, and 11 had cancers of unknown origin. Diagnoses of the primary lesions were confirmed using the MPE cellblock method for seven of 11 patients (63.6%), by excisional biopsy or aspiration from other sites in four of nine patients, by exploratory laparotomy in two of three patients, and by peritoneal washing cytology in five patients. CONCLUSION: Lung cancer and cancer of unknown origin are major causes of MPE at initial presentation. However, these groups also contain cancers that are curable and those with good long-term prognosis. The MPE cellblock method represents an accurate method for identifying cancer origin. PMID- 26816538 TI - Clinical evaluation of postoperative chemotherapy based on genetic testing in patients with stage IIIA non-small cell lung cancer. AB - BACKGROUND: We performed a retrospective analysis to evaluate whether a postoperative chemotherapy selection method based on four tumoral gene expression tests would improve prognosis in patients with stage IIIA non-small cell lung cancer (NSCLC) after surgery. METHODS: Between January 2007 and July 2011, 148 patients with stage IIIA NSCLC underwent radical lobectomy with four cycles of adjuvant postoperative chemotherapy. Forty-five patients had tailored treatment plans based on the results of tumoral gene expression tests. The tests consisted of quantitative real-time polymerase chain reaction analyses to measure the messenger ribonucleic acid levels of the excision repair cross-complementing gene 1, ribonucleotide reductase Ml, type III beta-tubulin, and thymidylate synthase genes in tumor tissues. One hundred and three patients received conventional chemotherapy. Disease responses were assessed after two cycles and every three months after the first four cycles of chemotherapy. The one and two-year survival rates and diesease-free survival (DFS) rates were recorded, and the adverse effects documented. RESULTS: The one and two-year DFS rates in the genetically tested group were better than those in the non-tested group, and the differences were statistically significant (P < 0.05). The two-year Kaplan-Meier DFS curve analysis results were significantly better in the genetically tested group (X(2) = 8.228, P = 0.004). The adverse effects during the treatments were not significantly different (P > 0.05) between the two groups. CONCLUSIONS: The chemotherapy selection method based on four tumoral gene expression tests demonstrated its feasibility to improve the efficacy of adjuvant postoperative chemotherapy and benefit stage IIIA NSCLC patients by yielding better DFS without increasing the adverse effects of chemotherapy. PMID- 26816539 TI - Rad51 in regulating the radiosensitivity of non-small cell lung cancer with different epidermal growth factor receptor mutation status. AB - BACKGROUND: Non-small cell lung cancer (NSCLC) harboring kinase-domain mutations in epidermal growth factor receptors (EGFR) has been observed to be sensitive to ionizing radiation (IR). We explore Rad51-dependent homologous recombination (HR) DNA repair in regulating radiosensitivity in two NSCLC cell lines with different EGFR mutation status. METHODS: NSCLC cell lines, wild-type EGFR A549 and mutant EGFR H820 with an in-frame deletion in exon 19 of EGFR (DeltaE746-E750), were cultured. Radiosensitivity was estimated by colony forming assay. Rad51 expression was evaluated by quantitative real time-polymerase chain reaction and Western-blot. Lentiviral small hairpin ribonucleic acid-Rad51 and DeltaE746-E750 deletion mutant EGFR were constructed and transfected into cells. Flowcytometry assay was used to analyze DNA double strand breaks, cell cycle alterations, and apoptosis. RESULTS: A549 had a higher survival factor (SF)2 (0.66 vs. 0.44) and lower alpha/beta value (4.07 vs. 9.01). Compared with the A549 cell, the H820 cell exhibited defective arrest in the S-phase, a higher rate of G2/M accumulation, early apoptosis, and residual gamma-H2AX. Downregulated Rad51 expression decreased SF2 (0.42 vs. 0.31) and increased the alpha/beta ratio (7.51 vs. 10.5), G2/M accumulation, early apoptosis, and gamma-H2AX in two cell lines. H820 had a low IR-induced Rad51 expression and nuclear translocation. Exogenous expression of the DeltaE746-E750 deletion mutant EGFR caused the A549 cell to become more radiosensitive. CONCLUSIONS: An EGFR mutated NSCLC cell line is sensitive to IR , which is correlated with reduced IR-induced Rad51 expression and nuclear translocation. The signaling pathway of EGFR maintaining Rad51 protein levels maybe a novel lung cancer therapeutic target to overcome radioresistance. PMID- 26816540 TI - Body mass index and exon 19 mutation as factors predicting the therapeutic efficacy of gefitinib in patients with epidermal growth factor receptor mutation positive non-small cell lung cancer. AB - BACKGROUND: Many randomized clinical trials have demonstrated that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are advantageous over standard chemotherapy, either as front-line treatment or as further management of patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC). However, which subgroup of these patients could benefit more from EGFR TKIs needs to be further explored. In the present study, we explored the predictive factors in such cohorts of patients who received gefitinib. METHODS: The study included 95 patients with EGFR mutation-positive advanced NSCLC who received gefitinib treatment. Multivariate analysis of progression-free survival (PFS) was performed using classification and regression tree (CART) analysis to assess the effect of specific variables on PFS in subgroups of patients with similar clinical features. RESULTS: The median PFS in patients with EGFR mutation positive advanced NSCLC who received gefitinib treatment was 13.3 months (95% confidence interval 9.4-17.2). CART analysis showed an initial split on body mass index (BMI); subsequently, three terminal subgroups were formed. The median PFS in the three subsets ranged from 8.2 to 15.2 months, in which the subgroup with a BMI less than or equal to 20.8 kg/m(2) had the longest PFS (15.2 months). In addition, PFS in the EGFR exon 19 mutation group was better than in the other mutation site group (10.3 vs. 8.2 months). CONCLUSIONS: BMI and exon 19 mutation may be predictors of PFS in patients with EGFR mutation-positive advanced NSCLC who receive gefitinib treatment. Both active EGFR mutation and patient-specific factors may be used to predict the therapeutic efficacy of EGFR-TKIs. PMID- 26816541 TI - Improvements to bronchoscopic brushing with a manual mapping method: A three-year experience of 1143 cases. AB - BACKGROUND: Conventional bronchoscopy with brushing alone for diagnosing peripheral pulmonary lesions (PPLs) is of low sensitivity. A manual mapping method was introduced and evaluated in this study, which could be routinely applied with bronchoscopic brushing to improve the sensitivity for malignant PPLs. METHODS: This mapping method involves the bronchoscopist drawing the route with a series of bronchial opening sketches and marking the leading bronchus at every bifurcation point based on thin-section computed tomography. This map is then used to guide bronchoscope insertion for brushing. A cross-sectional study on the evaluation of this method for the diagnosis of malignant PPLs was conducted on patients from July 2010 to June 2013. RESULTS: The sensitivity for malignant PPLs of conventional brushing, conventional brushing with mapping on a portion of patients, and conventional brushing with mapping method increased from 17.0% to 25.8% to 31.5% (P < 0.001), respectively. For lesion sizes over 3 cm, the rate of these three groups increased from 25.1% to 38.6% to 50.9% (P < 0.001), respectively. The sensitivity of this mapping method for malignant PPLs was statistically associated with lesion size, lesion character, relationship between the lesion and the leading bronchus, linear distance between the targeted bronchus and the opening of the lobe bronchus, and accessibility (P < 0.001, P = 0.039, P < 0.001, P = 0.031, and P = 0.020, respectively). CONCLUSIONS: The manual mapping method greatly increased the bronchoscopic brushing sensitivity for malignant PPLs compared to the conventional brushing method. During routine clinical work, it is economical and convenient for guiding bronchoscope insertion. PMID- 26816542 TI - Management of post-pneumonectomy syndrome using tissue expanders. AB - BACKGROUND: Post-pneumonectomy syndrome (PPS) is a rare syndrome characterized by trachea-bronchial stenosis and severe dyspnea. In this study, we retrospectively evaluated the clinical outcomes in patients who underwent placement of tissue expanders for PPS. METHODS: Data from patients who underwent placement of tissue expanders for PPS were analyzed for preoperative characteristics, surgical techniques, and postoperative outcomes. Between 1997 and 2014, a total of 10 patients were treated for PPS by tissue expanders. RESULTS: The median age of the 10 patients was 45 years (range, 16-70). Four patients had undergone right pneumonectomy, three patients had undergone left pneumonectomy, and three patients had post-pneumonectomy-like syndrome. Preoperatively, seven patients initially received high oxygen therapy for hypoxemia but progressed to respiratory failure, and three patients required mechanical ventilator support. Among these three patients, one required intraoperative extracorporeal membrane oxygenation support because of sudden cardiac arrest during preparation for surgery. The median follow-up was 59.5 months (range, 2-204). The median interval between pneumonectomy and repositioning was 13 months (range, 8-581). Two patients underwent placement of a single tissue expander, and two tissue expanders were placed in eight of the 10 patients. The median volume of tissue expanders inflated with saline was 450 cc (range, 60-850 cc) per tissue expander. There was no perioperative mortality in our study. Complications occurred in four patients (40%). CONCLUSIONS: Repositioning of the mediastinum with placement of a saline filled tissue expander for PPS is very effective for the relief of symptoms, with low mortality. PMID- 26816543 TI - Lung cancer incidence and mortality in China, 2011. AB - BACKGROUND: The National Central Cancer Registry (NCCR) of China is responsible for cancer surveillance. Cancer registration data from registries located in each province are submitted annually to the NCCR for analysis and publication. The lung cancer incidences, and mortalities were estimated in 2011 in China by NCCR. METHODS: In 2014, 234 population-based cancer registries' data in 2011 were submitted to the NCCR and 177 cancer registries' data were selected after quality evaluation. The selected data were classified into urban and rural areas; the crude incidence and mortality rates of lung cancer were calculated by age and gender. Age-standardized rates were calculated by China and World standard population. The 6(th) National Population Census data of China was used to estimate the 2011 lung cancer burden in China. RESULTS: Lung cancer remained the most common cancer and the leading cause of cancer death in China in 2011. Lung cancer incidence and mortality were higher in men and urban areas than those in women and rural areas. The rates were relatively low in patients under 40 years of age, and dramatically increased after age 40, reaching a peak in patients aged 80-84. CONCLUSION: The burden of lung cancer was serious in China in 2011, especially for men in urban areas. Effective methods of intervention, such as air pollution and smoking controls, should be enhanced in the future. PMID- 26816544 TI - Status and perspectives of detection by low-dose computed tomography or computed radiography in surgical patients with lung cancer, based on a five-year study. AB - BACKGROUND: A retrospective study involving 502 lung cancer patients who had received pulmonary resection from 2009-2013 was conducted in order to compare the clinical characteristics of patients whose diagnosis was detected by low-dose computed tomography (LDCT) and computed radiography (CR). METHODS: Two groups were established, based on the method of detection: the LDCT group included 172 lung cancer patients; the CR group included 330 lung cancer patients. The evolution of proportions of patients in urban and rural regions was also analyzed, according to detection method. RESULTS: The percentage of patients with stage I was higher in the LDCT group than in the CR group (77.3%, 133/172 vs. 53.6%, 177/330). The incidence of postoperative complications within 30 days was significantly lower in the LDCT than in CR group (25.0% vs. 33.6%). The proportion of patients detected by LDCT or CR in urban regions was constantly higher than in rural regions (with an increase of 13.0% vs. 5.9%); the proportion of LDCT-detected patients in urban regions was constantly higher than in rural regions (with an increase of 8.7% vs. 5.9%). CONCLUSIONS: LDCT contributes to a higher proportion of early lung cancer diagnoses and a lower incidence of postoperative complications in surgical patients. The proportions of patients detected early and by LDCT have both increased steadily during the last five years. These two trends are more pronounced in urban compared with rural patients. PMID- 26816545 TI - Efficacy and adequacy of conventional transbronchial needle aspiration of IASLC stations 4R, 4L and 7 using endobronchial landmarks provided by the Wang nodal mapping system in the staging of lung cancer. AB - BACKGROUND: The role of transbronchial needle aspiration (TBNA) in the diagnosis and staging of lung cancer has been well established. Recently, the efficacy of conventional TBNA in the staging of lung cancer has been enhanced by the use of endobronchial ultrasound (EBUS)-TBNA. Our study sought to evaluate the adequacy of TBNA of International Association for the Study of Lung Cancer (IASLC) stations 4R, 4L and 7 using endobronchial landmarks provided by the Wang nodal mapping system in the staging of lung cancer. METHODS: We retrospectively analyzed all bronchoscopic cases with conventional TBNA punctures positive for malignancy at our institution from 1 January to 31 October 2014. The endobronchial puncture site was guided by the Wang nodal mapping system. The Wang stations were correlated with the IASLC lymph node map. No endobronchial ultrasound or rapid on-site evaluation was used. Pathological analysis included cytological and histological examination. RESULTS: Diagnosis by histological analysis was obtained in 115 (55.3%) out of 208 puncture sites. The metastatic lymph nodes were distributed at IASLC stations 4R (W1, 3, 5) 46.6 %, 7 (W2, 8, 10) 19.7%, 4L (W4, 6) 11.5%, 11R (W7, W9) 11.1% 11L (W11) 9.6%, 2R (high station W3) 0.5%, and the proximal portion of station 8 (station W10 beyond the middle lobe orifice) 1%. No complications were observed. CONCLUSION: IASLC station 4R (W1, 3, 5), 7 (W2, 8, 10) and 4L (W4, 6) are adequate for the staging of lung cancer. PMID- 26816546 TI - Notch1 controls cell chemoresistance in small cell lung carcinoma cells. AB - BACKGROUND: Small cell lung carcinoma (SCLC) is characterized by a high rate of relapse and failure of chemotherapy because of the emergence of drug resistant cells. Notch signaling controls carcinogenesis in several human malignancies and could be involved in the resistance of cells to several chemotherapeutic agents. Herein, we analyzed the role of Notch1 signaling in the resistance of human SCLC cells to doxorubicin. METHODS: Small interfering ribonucleic acid technology was used to knock down (KD) Notch1 in H69AR and SBC-3 SCLC cells. We detected the effect of inhibiting Notch1 on the expression of drug resistant related molecules: multidrug resistance-associated protein (MRP-1) and anti-apoptotic factor B-cell lymphoma-2, as well as to cell adhesion molecule E-cadherin, which contributes to the adhesion of SCLC cells to the extracellular matrix and confers chemoresistance in a process known as cell adhesion-mediated drug resistance (CAM DR). We also observed the effect of KD Notch1 on cell survival under high concentrations of doxorubicin treated media. RESULTS: H69AR and SBC-3 cells expressed Notch1 protein and grew as adherent aggregates, which confer resistance to high concentrations of doxorubicin. On inhibiting Notch1, we observed activation of the apoptotic pathway in cells, possibly resulting from the loss of CAM-DR and, thus, SBC-3 cells showed a loss of chemoresistant ability. However, in H69AR cells with KD Notch1, the expression of MRP-1 was increased and, thus, sustained the chemoresistant ability of cells. CONCLUSION: The Notch1 signaling pathway is involved in mediating the drug resistance phenotype of SCLC cells. PMID- 26816548 TI - Efficacy and safety of recombinant human tumor necrosis factor application for the treatment of malignant pleural effusion caused by lung cancer. AB - Malignant pleural effusion (MPE) signifies a poor prognosis for patients with lung cancer. For treating physicians, the primary goals are to achieve sufficient control of MPE and minimize invasive intervention. Recombinant human mutant tumor necrosis factor-alpha (rhu-TNF) has been used in the treatment of MPE. The aim of our research was to evaluate the efficacy and safety of rhu-TNF application via ultrasound-guided chest tube for the treatment of MPE. rhu-TNF was administered as a single dose to 102 patients with MPE caused by lung cancer, and dexamethasone (Dxm, 5 mg) was administered 30 minutes before rhu-TNF in 35 randomly selected patients in order test its ability to prevent side effects. The primary endpoint was the efficacy of the rhu-TNF treatment (disease response rate) and side effects (pain, fever, and flu-like symptoms), evaluated four weeks after instillation. The disease response rate of rhu-TNF treatment was 81.37%. Side effects included 13 (12.75%) patients complaining of flu-like symptoms, 15 (14.71%) with fever/chill, and 14 (13.73%) with chest pain. A significantly higher efficacy was observed for treatment with 3 MU versus 2 MU of rhu-TNF (P = 0.036), while the adverse effects were similar. There was no significant association between the dose of rhu-TNF and progression-free survival (P = 0.752). In conclusion, our study shows that intra-pleural instillation of rhu-TNF achieves sufficient control of MPE and minimizes invasive intervention. PMID- 26816547 TI - Diagnosis of the invasiveness of lung adenocarcinoma manifesting as ground glass opacities on high-resolution computed tomography. AB - BACKGROUND: To explore the diagnostic method in assessing the malignancy of pulmonary adenocarcinoma characterized by ground glass opacities (GGO) on computed tomography (CT). METHODS: Preoperative CT data for preinvasive and invasive lung adenocarcinomas were analyzed retrospectively. GGO lesions that were detected on lung windows but absent using the mediastinal window were subject to adjustment of the window width, which was reduced with the fixed interval of 100 HU until the lesions were no longer evident, with a fixed mediastinal window level of 40 HU. The shape, smoking habits, size of the lesion on the lung window, and window width at which lesions disappeared were compared and receiver operating characteristic curves were used to determine the optimal cut-off of the lesion size and window width to differentiate between these invasive and preinvasive lesions. RESULTS: Of the 209 lung adenocarcinomas, 102 were preinvasive (25 atypical adenomatous hyperplasia and 77 adenocarcinoma in situ), while 107 were invasive (78 minimally invasive adenocarcinoma and 29 invasive adenocarcinoma). The shape, lesion size, and window width at which lesions were no longer evident differed significantly between the two groups (P < 0.05). The size of 8.9 mm and a window width of 1250 HU were the optimal cut-off to differentiate between preinvasive and invasive lesions. CONCLUSION: The shape, size of the lesion, and window width on high-resolution CT may be useful in assessing the invasiveness of lung adenocarcinoma that manifests as GGO. Irregular lesions that disappear at window width <1250 HU, with a diameter of > 8.9 mm are more likely to be invasive. PMID- 26816549 TI - Primary extranodal natural killer/T-cell lymphoma of bronchus and lung: A case report and review of literature. AB - Primary pulmonary non-Hodgkin's lymphoma (NHL) is very rare. It represents less than 1% of all NHL, and 0.5-1% of all primary pulmonary malignancies. Almost all cases of primary pulmonary NHL originate from B-cell lineage. We present a case of a 53-year-old man with primary extranodal NK/T-cell lymphoma of the bronchus and lung, presented progressive dyspnea caused by right lower lung consolidation, and pleural effusion. Initial chest computed tomography suggested advanced lung cancer. Bronchofiberscopy showed a polypoid tumor on which a biopsy was performed. Histologically, the diffusely infiltrative atypical cells were positive for cytoplasmic CD3, CD56, granzyme B, and negative for cytokeratin, CD20 immunostains, suggesting NK/T cell lineages. In situ hybridization for Epstein-Barr virus encoded ribonucleic acid (EBER) was positive. Herein, we discuss the clinicopathological features of this case and review the literature on primary extranodal NK/T-cell lymphoma of the lung. Compared with other patients, who died after the first cycle of chemotherapy and/or within three months, our patient had longer survival under aggressive chemotherapy and auto peripheral blood stem cell transplantation. PMID- 26816550 TI - Computed tomography-guided percutaneous microwave ablation of early stage non small cell lung cancer in a pneumonectomy patient. AB - A squamous cell lung cancer patient was treated with pneumonectomy. A recurrent lung cancer (adenocarcinoma) was found 45 months later and successfully biopsied and treated with microwave ablation. After 18 months of follow up, no evidence of tumor recurrence was observed. PMID- 26816551 TI - Video-assisted thoracoscopic surgery in the treatment of non-small-cell lung cancer complicated with left atrial tumor thrombus. AB - We report a case of pulmonary squamous cell carcinoma complicated with a tumor thrombus in the left atrium. The left atrial tumor thrombus, together with the left lower lobe, was removed via complete video-assisted thoracoscopic surgery (VATS), with cardiopulmonary bypass standby. The patient recovered well from surgery, received four cycles of postoperative chemotherapy, and is now under follow-up at the outpatient clinic. Although the optimal treatment is still controversial, simultaneous VATS and atriotomy under the premise of preoperative evaluation of the thrombus, including size and extent, might prevent systemic embolization and sudden death, alleviate the wound, promote postoperative rehabilitation, and improve prognosis in selected patients. PMID- 26816552 TI - Draft Genome Sequences of Two Brucella abortus Strains Isolated from Cattle and Pig. AB - We report the draft genome sequences of two Brucella abortus strains LMN1 and LMN2 isolated from cattle and pig. The LMN1 and LMN2 have the genome size of 3,395,952 bp and 3,334,792 bp, respectively. In addition to the conserved genes of Brucella, few novel regions showing similarity to the phages were identified in both strains. PMID- 26816553 TI - Draft Genome of Multidrug-Resistant Klebsiella pneumoniae 223/14 Carrying KPC-6, Isolated from a General Hospital in Malaysia. AB - We performed whole genome sequencing on a clinical multidrug-resistant Klebsiella pneumoniae strain 223/14. Investigation into its draft genome revealed the presence of KPC-6 variant, suggesting carbapenemase is present in this isolate. We found a plasmid-borne KPC gene (882 bp) inserted between two transposase genes in the genome of K. pneumoniae 223/14. PMID- 26816554 TI - Loss of nuclear localization of TET2 in colorectal cancer. AB - 5-Hydroxymethylcytosine (5hmC) is lost in multiple human cancers, including colorectal cancer (CRC). Decreased ten-eleven translocation 1 (TET1) messenger RNA (mRNA), but not other two TET family members, has been observed in the colorectal cancer and is crucial for colorectal cancer initiation. Here, we show that nuclear localization of TET2 was lost in a significant portion of CRC tissues, in association with metastasis. In CRC cells, nuclear expression of TET2 were absent but not TET3. Nuclear export inhibitor can increase the 5hmC level in CRC cells, probably through regulating TET2. Our results indicate a new mechanism of TET2 dysregulation in colorectal cancer. PMID- 26816555 TI - An Algorithm for Building an Electronic Database. AB - OBJECTIVE: We propose an algorithm on how to create a prospectively maintained database, which can then be used to analyze prospective data in a retrospective fashion. Our algorithm provides future researchers a road map on how to set up, maintain, and use an electronic database to improve evidence-based care and future clinical outcomes. METHODS: The database was created using Microsoft Access and included demographic information, socioeconomic information, and intraoperative and postoperative details via standardized drop-down menus. A printed out form from the Microsoft Access template was given to each surgeon to be completed after each case and a member of the health care team then entered the case information into the database. RESULTS: By utilizing straightforward, HIPAA-compliant data input fields, we permitted data collection and transcription to be easy and efficient. Collecting a wide variety of data allowed us the freedom to evolve our clinical interests, while the platform also permitted new categories to be added at will. CONCLUSION: We have proposed a reproducible method for institutions to create a database, which will then allow senior and junior surgeons to analyze their outcomes and compare them with others in an effort to improve patient care and outcomes. This is a cost-efficient way to create and maintain a database without additional software. PMID- 26816556 TI - Desmoplastic Melanoma: Clinical Behavior and Management Implications. AB - INTRODUCTION: Desmoplastic melanoma is a rare variant of melanoma that has been reported to demonstrate unique clinical behavior when compared with other histological subtypes. In this study, we present the clinical course of patients with this unusual diagnosis. We hypothesized that desmoplastic melanoma would differ from nondesmoplastic melanoma with regard to its presentation, rate of regional metastasis, and recurrence pattern. METHODS: After institutional review board approval, a retrospective chart review was performed on all patients with a diagnosis of desmoplastic melanoma since 1998. The following data were collected: patient demographics, histopathological details of the lesion, initial treatment, and clinical course. In addition, the available slides were reviewed by a dermatopathologist. RESULTS: Twenty-eight patient charts were reviewed. Mean age at diagnosis was 65 years. Fifty-seven percent of patients were men, and 67% of the lesions originated from the head and neck. Of the 28 patients, 11 had pathology slides that were adequate for evaluation. Pure desmoplastic melanoma, defined by more than 90% of the specimen demonstrating desmoplastic features, was found in only 3 patients. Taking into account all cases, the mean Breslow thickness was 5.09 mm and ulceration was present in 12.5% of lesions. Regional disease was discovered in 18% of patients. The mean follow-up time was 43 months, and the overall recurrence rate was 32%. 66.7% of first recurrences were local. Two of 3 patients with pure desmoplastic melanoma developed regional metastasis. CONCLUSIONS: Our data largely support previous studies that suggest desmoplastic melanoma behaves differently compared with other histological subtypes. However, the incidence of regional disease among patients with pure desmoplastic melanoma appears to be higher in our study than in previous reports. Although this rare variant typically presents with advanced local disease, the rate of regional metastasis is less than what would be expected for similar thickness, nondesmoplastic cutaneous melanoma. The recurrence pattern is different compared with nondesmoplastic melanoma, and the most common site of recurrence is local. Discrepancy in the literature regarding the clinical behavior of this disease may be related to inconsistent pathological criteria for diagnosis. Further research will help clarify the optimal management of desmoplastic melanoma. PMID- 26816557 TI - A Triple Pedicle, Near-Total Thigh Flap Supercharged With the Flow-Through Technique. AB - This is the first instance where the technique of supercharging a flap with a second pedicle, combined with a third pedicle using the flow-through technique, is described in literature. We present the case of a 66-year-old man with multiple recurrent squamous and basal cell carcinomas of the face. He underwent a wide local excision resulting in a 20 * 26-cm defect. This was reconstructed with near-total thigh free flap. Three separate pedicles providing independent perforators to the medial, posterior-lateral, and anterolateral thigh from the superficial femoral artery, directly from the profunda femoris artery, and from the descending branch of the lateral circumflex artery were harvested. We expand upon the technique of supercharging a flap by not only anastomosing 3 separate pedicles but also using the flow-through technique to provide inflow and outflow to the third pedicle. PMID- 26816558 TI - Bilateral Reduction Mammaplasty as an Oncoplastic Technique for the Management of Early-Stage Breast Cancer in Women with Macromastia. AB - OBJECTIVE: Lumpectomy may result in contour deformities or breast asymmetry in women with breast cancer and macromastia. This study investigates the use of bilateral reduction mammaplasty, with the tumor and margins included within the reduction specimen. METHODS: Twenty-four patients who underwent lumpectomy with immediate bilateral reduction mammaplasty for unilateral breast cancer were included. Patient medical records were reviewed for demographic, oncological, and surgical characteristics. RESULTS: Mean patient age was 57 years, and mean body mass index was 32.2 kg/m(2). Mean tumor size was 1.7 cm. All tumor margins were free of neoplastic involvement. No difference was noted between the ipsilateral and contralateral resection weights (P = .81). Adjuvant radiation therapy was delivered to 21 patients (88%). There were no significant differences in postoperative total (P = .36), major (P = .44), or minor (P = .71) complications between the tumor and nontumor sides. Only 1 patient required additional revision surgery following the initial lumpectomy with bilateral reduction mammaplasty. CONCLUSION: Lumpectomy with bilateral reduction mammaplasty did not compromise surgical margins. Lumpectomy with bilateral reduction mammaplasty may allow for adequate surgical treatment of breast cancer while avoiding significant breast asymmetry in women with macromastia. PMID- 26816559 TI - Myxoid Dermatofibrosarcoma Protuberans of the Abdomen. PMID- 26816560 TI - Thumb Interphalangeal Joint Dislocation. PMID- 26816561 TI - Erratum: maternal mortality in Cameroon: a university teaching hospital report. AB - This erratum corrects article: "Maternal mortality in Cameroon: a university teaching hospital report." The Pan African Medical Journal. 2015;21:16. doi:10.11604/pamj.2015.21.16.3912[This corrects the article on p. 16 in vol. 21, PMID: 26401210.]. PMID- 26816562 TI - International Accreditation of Postgraduate Medical Education: Whither Its Role in Oman? PMID- 26816563 TI - Research Misconduct: The Peril of Publish or Perish. AB - There is a spurt of interest in research productivity in the Gulf Cooperation Council (GCC) to lay the foundation for national development. From a global perspective, increased research productivity could conceivably be accompanied by an exponential increase in research misconduct (RM). Inevitably, erroneous or falsified data will be expected to adversely affect public health by misleading policy makers and clinicians alike into embarking on health policy and allocation of resources that are byproducts of RM. This will contribute significantly to the emerging crisis of confidence of the public in the integrity of scientific research. For a long time, RM has been considered only as plagiarism or data fabrication and falsification. However, the concept of RM nowadays encompasses more and, in this review, we discuss its possible implications in emerging economies, such as those of the GCC countries. We suggest that GCC countries ought to consider implementing remedial and punitive policies to deal with RM. PMID- 26816564 TI - The Effect of Obesity on Pregnancy and its Outcome in the Population of Oman, Seeb Province. AB - OBJECTIVES: The World Health Organization estimated that in 2011 worldwide 1.6 billion adults were overweight, and 400 million were obese. The obesity epidemic is a documented phenomenon and Oman is no exception. The aim of this study was to determine the effect of obesity on pregnancy and its prenatal and neonatal outcomes. METHODS: A prospective cohort study was carried out among pregnant Omani women attending antenatal clinics in their first trimester in the Seeb province of Muscat, Oman. RESULTS: A total of 700 pregnant women were enrolled in the study and were categorized according to their body mass index: 245 (35%) were normal weight, 217 (31%) were overweight, and 238 (34%) were obese. The relative risk (RR) of cesarean section among obese women compared to women of normal weight was 2.1 (95% confidence interval (CI) 1.2-3.2) and of overweight women was 1.4 (95% CI 0.9-2.3). The risk of elective cesarean section increased to 7.5 (95% CI 1.7-32.8) in obese women and was statistically significant in the obese group. In this study, 100 women (15.7%) developed gestational diabetes (11.8% of normal weight women, 17.8% of overweight women, and 17.9% of obese women). Miscarriages were more common among obese women 11.9% (n = 27) compared to the normal weight and overweight groups (6.7% and 9.4%, respectively). There was a weak yet statistically significant correlation between birth weight and body mass index. The risk of macrosomia was significantly higher in obese women compared to normal weight women. To evaluate the sensitivity of the oral glucose challenge test (OGCT), the oral glucose tolerance test (OGTT) was measured in 203 participants (29%) who had a normal OGCT result. It was found that 14.5% of overweight women and 13.5% of normal weight women had an abnormal OGTT result even when their OGCT result was normal. CONCLUSIONS: Obesity is associated with an increased risk of cesarean section (especially elective cesarean), gestational hypertension, macrosomia, and miscarriage. It also increases the risk of gestational diabetes. PMID- 26816565 TI - The Relationship Between Dietary Intakes of Amino Acids and Bone Mineral Density Among Individuals with Spinal Cord Injury. AB - OBJECTIVES: The effect of dietary protein intake on bone mineral density (BMD) has not been explained in patients with spinal cord injury (SCI). In this study, we looked at the relationship between BMD and higher protein intake in patients with SCI while controlling for possible confounders. METHODS: Patients with SCI, who were referred to the Brain and Spinal Cord Injury Research Center between November 2010 and April 2012, were included in the study. In total, the dietary intakes of 103 patients were assessed by 24-hour dietary recall interviews. We used dual-energy X-ray absorptiometry to measure BMD in the femoral neck, trochanter, intertrochanteric zone, hip, and lumbar vertebras. RESULTS: Eighty six men and 17 women participated in this study. Protein intake was negatively associated with the BMD of lumbar vertebrae (p = 0.001, r = -0.37 for T-score and p = 0.030, r = -0.24 for Z-score). The BMD of lumbar vertebrae were negatively associated with intake of tryptophan, isoleucine, lysine, cysteine, and tyrosine (p = 0.007, 0.005, 0.009, 0.008, and 0.008 for T-score, respectively). Higher intakes of threonine, leucine, methionine, phenylalanine, valine, and histidine were related to a lower BMD of lumbar vertebrae (p = 0.006, 0.010, 0.009, 0.010, 0.009, and 0.008 respectively for T-scores). CONCLUSIONS: We found that high protein intake led to a lower BMD of lumbar vertebrae in patients with SCI after controlling for confounders including demographic and injury-related characteristics and calcium intake. No relationship between higher amino acids intake and BMD of the femur and hip was detected. Intake of alanine, arginine, and aspartic acid were not related to BMD. PMID- 26816566 TI - From Symptoms to Diagnosis: An Observational Study of the Journey of Rheumatoid Arthritis Patients in Saudi Arabia. AB - OBJECTIVES: Rheumatoid arthritis (RA) is often not diagnosed or treated quickly enough to alter outcomes. We aimed to evaluate the lag times from disease onset to first clinical consultation and diagnosis and to identify factors contributing to delayed diagnosis in Saudi Arabia. METHODS: This retrospective, multicenter study collected data on 250 patients, from six hospitals in Saudi Arabia, who met the 2010 American College of Rheumatology criteria for RA. RESULTS: The patients mean age was 43.3+/-12.0 years (mean disease duration: 6.6+/-5.8 years). The majority were female (84.8%) and presented with joint pain during RA onset (83.6%). On average, they consulted 4.3+/-2.5 physicians from the first symptoms to the final diagnosis. The mean time from onset to first physician visit (lag 1) was 6.2+/-5.5 months, whereas the mean time was 30.2+/-16.0 months between the initial visit and final RA diagnosis (lag 2). Only 3.2% of patients initially sought consultation from a rheumatologist, while 67.2%, 23.6%, and 6.0% first met with orthopedic surgeons, general practitioners, and non-rheumatologists, respectively. Non-rheumatologists offered diagnoses in 24.4% of cases while rheumatologists diagnosed 75.6%. The absence of early hand/wrist involvement and fatigue were associated with delayed RA diagnosis (long lag 2; p<0.010). Moreover, geographic distribution influenced RA diagnosis, with rural patients experiencing a greater delay than urban patients (p<0.0001). CONCLUSIONS: Failure of patients to be seen by rheumatologists at RA onset delayed diagnosis and treatment. Thus, RA diagnosis can be accelerated by encouraging early referral to rheumatologists. PMID- 26816567 TI - Patterns of Antimicrobial Prescribing in a Tertiary Care Hospital in Oman. AB - OBJECTIVES: Antimicrobial stewardship programs have been designed to measure and improve the use of antimicrobials to achieve optimal clinical outcomes and reduce bacterial resistance. The aim of this study was to review patterns of antimicrobial prescribing for hospitalized patients in the acute care setting and assess the appropriateness of antimicrobial use among prescribers in a tertiary care hospital in Oman. METHODS: We conducted a retrospective audit of the appropriateness of antimicrobial prescribing in patients admitted to acute care settings in a tertiary care hospital in Oman over a four-week period (1 November to 28 November 2012). The data of all discharged patients were retrieved from the department databases. Patient records and prescriptions were reviewed by an infectious disease consultant. The rationality of antimicrobial use was evaluated, analyzed, and judged based on local standard guidelines and the experience of the evaluating consultant. RESULTS: There were 178 patients discharged from acute medical teams over the study period. Sixty-four percent of the patients received a total of 287 antimicrobial agents during admission. The average number of antimicrobials prescribed per patient in those prescribed antimicrobials was 2.5+/-1.1. The most commonly prescribed antimicrobial agent was piperacillin/tazobactam. Most patients had infections from gram-negative organisms, and high rates of extended spectrum beta-lactamase producing organisms were observed. Cultures were obtained before antimicrobial initiation in 25% of patients. Variability in antimicrobial selection for common infections was observed. CONCLUSIONS: National guidelines for the management of common infections are needed to minimize the overuse and misuse of antimicrobial agents in tertiary care hospitals. A large surveillance study on antimicrobial prescribing appropriateness in different hospital settings is warranted. PMID- 26816568 TI - Malignant Gastric Glomus Tumor: A Case Report and Literature Review of a Rare Entity. AB - A glomus tumor is a mesenchymal neoplasm that usually develops in the peripheral soft tissue, especially in the distal part of the extremities. The subungual zones of the fingers and toes are the most frequent sites of observation. The majority of glomus tumors are entirely benign, and the malignant counterparts are very rare, especially those arising in the visceral organs. We report a case of an extremely rare malignant glomus tumor arising in the stomach of a 53-year-old female admitted to the King Khalid University Hospital, Saudi Arabia. The patient reported a four-month history of pain and fullness in the left hypochondrium. She underwent laparotomy and resection of the gastric mass. The mass was analysed by histopathology. Based on the pathological findings of large tumor size, nuclear atypia, increased mitotic rate, atypical mitosis, the presence of necrosis, and characteristic immunohistochemistry the diagnosis of malignant glomus tumor was rendered. Ultrastructural study confirmed the diagnosis. The patient is well and continues regular follow-up. PMID- 26816569 TI - Diclofenac-Induced Photo-Onycholysis. AB - Onycholysis is the detachment of the nail plate from the nail bed. If drug induced, it can be an isolated phenomenon, but it may also accompany or follow a cutaneous phototoxicity reaction due to drug intake and exposure to ultraviolet irradiation. Photo-onycholysis is a rare photosensitivity reaction due to exposure to either a natural or artificial source of light. Many drugs are responsible for this phototoxic reaction, especially tetracyclines, psoralens, chloramphenicol, non-steroidal anti-inflammatory drugs, fluoroquinolones, and, rarely, doxycycline. Any patient given enough of a therapeutic dose of an inducing drug and sufficient light irradiation can develop phototoxic reactions. While there is no need to avoid these drugs completely, precautions should be taken. Here we have reported the case of a patient who developed onycholysis of his fingernails with sparing of the toenails following administration of diclofenac therapy for lower back pain. The onycholysis was associated with a phototoxic reaction. The swellings resolved totally within two days, and the patient started to notice the separation of all fingernail plates from their nail beds. The patient was treated symptomatically. On follow-up, onycholysis had regressed slowly, and the condition recovered totally within three months without any sequelae. PMID- 26816570 TI - Surgical Management of Bulky Mediastinal Metastases in Follicular Thyroid Carcinoma. AB - Follicular thyroid adenoma and carcinoma are very common. Benign and malignant lesions are usually indistinguishable from cytology alone and often require confirmatory resection. The spread of follicular carcinoma is usually hematogenous and is treated with surgery and adjuvant radioactive iodine. Very rarely, metastases occur in the mediastinum. Patients usually present with severe compressive symptoms. With proper treatment and follow-up, the prognosis for these type of thyroid malignancies is excellent. In the case presented here, our patient presented to the Universiti Kebangsaan Malaysia Medical Center with a progressively enlarging anterior neck swelling. The swelling had started 10 years before his presentation. We diagnosed him with an advanced thyroid malignancy with bulky mediastinal metastases. After extensive investigations and counseling, we chose to treat the patient with tumor excision and mediastinal metastases resection. Typically, mediastinal resection involves the removal of the sternum and use of an acrylic implant to recreate the sternum. In this case, the sternum and ribs were removed with subsequent myocutaneous flap coverage for the wound defect. Our experience represents an alternative treatment option in cases where implant use is unsuitable. PMID- 26816571 TI - Study of the most frequent natural tooth colors in the Spanish population using spectrophotometry. AB - PURPOSE: To identify the most frequent natural tooth colors using the Easyshade Compact (Vita -Zahnfabrik) spectrophotometer on a sample of the Spanish population according to the 3D Master System. MATERIALS AND METHODS: The middle third of the facial surface of natural maxillary central incisors was measured with an Easyshade Compact spectrophotometer (Vita Zahnfabrik) in 1361 Caucasian Spanish participants aged between 16 and 89 years. Natural tooth color was recorded using the 3D Master System nomenclature. The program used for the present descriptive statistical analysis of the results was SAS 9.1.3. RESULTS: The results show that the most frequent dental color in the total sample studied is 3M1 (7.05%), followed by the intermediate shade 1M1.5 (6.91%) and 2L1.5 (6.02%). CONCLUSION: According to the research methodology used, and taking into account the limitations of this study, it can be proposed that the most frequent color among the Spanish population is 3M1; the most common lightness group is 2; the most frequent hue group according to the 3D Master System is M and the most frequent chroma group is 1.5. PMID- 26816572 TI - Evaluation of biogeneric design techniques with CEREC CAD/CAM system. AB - PURPOSE: The aim of this study was to evaluate occlusal contacts generated by 3 different biogeneric design modes (individual (BI), copy (BC), reference (BR)) of CEREC software and to assess the designs subjectively. MATERIALS AND METHODS: Ten pairs of maxillary and mandibular casts were obtained from full dentate individuals. Gypsum cast contacts were quantified with articulating paper and digital impressions were taken. Then, all ceramic crown preparation was performed on the left first molar teeth and digital impressions of prepared teeth were made. BI, BC, and BR crowns were designed. Occlusal images of designs including occlusal contacts were superimposed on the gypsum cast images and corresponding contacts were determined. Three designs were evaluated by the students. RESULTS: The results of the study revealed that there was significant difference among the number of contacts of gypsum cast and digital models (P<.05). The comparison of the percentage of virtual contacts of three crown designs which were identical to the contacts of original gypsum cast revealed that BI and BR designs showed significantly higher percentages of identical contacts compared with BC design (P<.05). Subjective assessment revealed that students generally found BI designs and BR designs natural regarding naturalness of fissure morphology and cusp shape and cusp tip position. For general occlusal morphology, student groups generally found BI design "too strong" or "perfect", BC design "too weak", and BR design "perfect". CONCLUSION: On a prepared tooth, three different biogeneric design modes of a CAD/CAM software reveals different crown designs regarding occlusal contacts and morphology. PMID- 26816573 TI - Impact of a "TED-Style" presentation on potential patients' willingness to accept dental implant therapy: a one-group, pre-test post-test study. AB - PURPOSE: A survey was conducted to assess the impact of a TED-like educational session on participants' willingness to accept dental implant therapy. MATERIALS AND METHODS: Volunteers interested in having information about dental implant therapies were recruited and asked to complete a two-part survey before and after an educational session. The initial survey elicited demographic information, self perceived knowledge on dental implants and willingness to this kind of treatment. A "TED-style" presentation that provided information about dental implant treatments was conducted before asking the participants to complete a second set of questions assessing the impact of the session. RESULTS: The survey was completed by 104 individuals, 78.8% were women and the mean age was 66.5+/-10.8. Before the educational session, 76.0% of the participants refused dental implants mainly due to lack of knowledge. After the educational session, the rejection of dental implants decreased by almost four folds to 20.2%. CONCLUSION: This study proved that an educational intervention can significantly increase willingness to accept treatment with dental implants in a segment of the population who is interested in having information about dental implant therapy. Furthermore, educational interventions, such as TED-like talks, might be useful to increase popular awareness on dental implant therapy. PMID- 26816575 TI - Effect of different veneering techniques on the fracture strength of metal and zirconia frameworks. AB - PURPOSE: To determine whether the fracture strengths and failure types differed between metal and zirconia frameworks veneered with pressable or layering ceramics. MATERIALS AND METHODS: A phantom molar tooth was prepared and duplicated in 40 cobalt-chromium abutments. Twenty metal (IPS d.SIGN 15, Ivoclar, Vivadent, Schaan, Liechtenstein) and 20 zirconia (IPS e.max ZirCAD, Ivoclar) frameworks were fabricated on the abutments. Each framework group was randomly divided into 2 subgroups according to the veneering material: pressable and layering ceramics (n=10). Forty molar crowns were fabricated, cemented onto the corresponding abutments and then thermocycled (5-55C, 10,000 cycles). A load was applied in a universal testing machine until a fracture occurred on the crowns. In addition, failure types were examined using a stereomicroscope. Fracture load data were analyzed using one-way ANOVA and Tukey HSD post-hoc tests at a significance level of 0.05. RESULTS: The highest strength value was seen in metal pressable (MP) group, whereas zirconia-pressable (ZP) group exhibited the lowest one. Moreover, group MP showed significantly higher fracture loads than group ZP (P=.015) and zirconia-layering (ZL) (P=.038) group. No significant difference in fracture strength was detected between groups MP and ML, and groups ZP and ZL (P>.05). Predominant fracture types were cohesive for metal groups and adhesive for zirconia groups. CONCLUSION: Fracture strength of a restoration with a metal or a zirconia framework was independent of the veneering techniques. However, the pressing technique over metal frameworks resisted significantly higher fracture loads than zirconia frameworks. PMID- 26816574 TI - Bonding values of two contemporary ceramic inlay materials to dentin following simulated aging. AB - PURPOSE: To compare the push-out bond strength of feldspar and zirconia-based ceramic inlays bonded to dentin with different resin cements following simulated aging. MATERIALS AND METHODS: Occlusal cavities in 80 extracted molars were restored in 2 groups (n=40) with CAD/CAM feldspar (Vitablocs Trilux forte) (FP) and zirconia-based (Ceramill Zi) (ZR) ceramic inlays. The fabricated inlays were luted in 2 subgroups (n=20) with either etch-and-bond (RelyX Ultimate Clicker) (EB) or self-adhesive (RelyX Unicem Aplicap) (SA) resin cement. Ten inlays in each subgroup were subjected to 3,500 thermal cycles and 24,000 loading cycles, while the other 10 served as control. Horizontal 3 mm thick specimens were cut out of the restored teeth for push out bond strength testing. Bond strength data were statistically analyzed using 1-way ANOVA and Tukey's comparisons at alpha=.05. The mode of ceramic-cement-dentin bond failure for each specimen was also assessed. RESULTS: No statistically significant differences were noticed between FP and ZR bond strength to dentin in all subgroups (ANOVA, P=.05113). No differences were noticed between EB and SA (Tukey's, P>.05) bonded to either type of ceramics. Both adhesive and mixed modes of bond failure were dominant for non aged inlays. Simulated aging had no significant effect on bond strength values (Tukey's, P>.05) of all ceramic-cement combinations although the adhesive mode of bond failure became more common (60-80%) in aged inlays. CONCLUSION: The suggested cement-ceramic combinations offer comparable bonding performance to dentin substrate either before or after simulated aging that seems to have no adverse effect on the achieved bond. PMID- 26816576 TI - Comparison of intraoral scanning and conventional impression techniques using 3 dimensional superimposition. AB - PURPOSE: The aim of this study is to evaluate the appropriate impression technique by analyzing the superimposition of 3D digital model for evaluating accuracy of conventional impression technique and digital impression. MATERIALS AND METHODS: Twenty-four patients who had no periodontitis or temporomandibular joint disease were selected for analysis. As a reference model, digital impressions with a digital impression system were performed. As a test models, for conventional impression dual-arch and full-arch, impression techniques utilizing addition type polyvinylsiloxane for fabrication of cast were applied. 3D laser scanner is used for scanning the cast. Each 3 pairs for 25 STL datasets were imported into the inspection software. The three-dimensional differences were illustrated in a color-coded map. For three-dimensional quantitative analysis, 4 specified contact locations(buccal and lingual cusps of second premolar and molar) were established. For twodimensional quantitative analysis, the sectioning from buccal cusp to lingual cusp of second premolar and molar were acquired depending on the tooth axis. RESULTS: In color-coded map, the biggest difference between intraoral scanning and dual-arch impression was seen (P<.05). In three-dimensional analysis, the biggest difference was seen between intraoral scanning and dual-arch impression and the smallest difference was seen between dual-arch and full-arch impression. CONCLUSION: The two- and three-dimensional deviations between intraoral scanner and dual-arch impression was bigger than full-arch and dual-arch impression (P<.05). The second premolar showed significantly bigger three-dimensional deviations than the second molar in the three-dimensional deviations (P>.05). PMID- 26816578 TI - Biomechanical three-dimensional finite element analysis of monolithic zirconia crown with different cement type. AB - PURPOSE: The objective of this study was to evaluate the influence of various cement types on the stress distribution in monolithic zirconia crowns under maximum bite force using the finite element analysis. MATERIALS AND METHODS: The models of the prepared #46 crown (deep chamfer margin) were scanned and solid models composed of the monolithic zirconia crown, cement layer, and prepared tooth were produced using the computer-aided design technology and were subsequently translated into 3-dimensional finite element models. Four models were prepared according to different cement types (zinc phosphate, polycarboxylate, glass ionomer, and resin). A load of 700 N was applied vertically on the crowns (8 loading points). Maximum principal stress was determined. RESULTS: Zinc phosphate cement had a greater stress concentration in the cement layer, while polycarboxylate cement had a greater stress concentration on the distal surface of the monolithic zirconia crown and abutment tooth. Resin cement and glass ionomer cement showed similar patterns, but resin cement showed a lower stress distribution on the lingual and mesial surface of the cement layer. CONCLUSION: The test results indicate that the use of different luting agents that have various elastic moduli has an impact on the stress distribution of the monolithic zirconia crowns, cement layers, and abutment tooth. Resin cement is recommended for the luting agent of the monolithic zirconia crowns. PMID- 26816577 TI - Partial denture metal framework may harbor potentially pathogenic bacteria. AB - PURPOSE: The aim of this study was to characterize and compare bacterial diversity on the removable partial denture (RPD) framework over time. MATERIALS AND METHODS: This descriptive pilot study included five women who were rehabilitated with free-end mandibular RPD. The biofilm on T-bar clasps were collected 1 week (t1) and 4 months (t2) after the RPD was inserted (t0). Bacterial 16S rDNA was extracted and PCR amplified. Amplicons were cloned; clones were submitted to cycle sequencing, and sequences were compared with GenBank (98% similarity). RESULTS: A total of 180 sequences with more than 499 bp were obtained. Two phylogenetic trees with 84 (t1) and 96 (t2) clones represented the bacteria biofilm at the RPD. About 93% of the obtained phylotypes fell into 25 known species for t1 and 17 for t2, which were grouped in 5 phyla: Firmicutes (t1=82%; t2=60%), Actinobacteria (t1=5%; t2=10%), Bacteroidetes (t1=2%; t2=6%), Proteobacteria (t1=10%; t2=15%) and Fusobacteria (t1=1%; t2=8%). The libraries also include 3 novel phylotypes for t1 and 11 for t2. Library t2 differs from t1 (P=.004); t1 is a subset of the t2 (P=.052). Periodontal pathogens, such as F. nucleatum, were more prevalent in t2. CONCLUSION: The biofilm composition of the RPD metal clasps changed along time after RPD wearing. The RPD framework may act as a reservoir for potentially pathogenic bacteria and the RPD wearers may benefit from regular follow-up visits and strategies on prosthesis-related oral health instructions. PMID- 26816579 TI - The effect of bacterial cellulose membrane compared with collagen membrane on guided bone regeneration. AB - PURPOSE: This study was to evaluate the effects of bacterial cellulose (BC) membranes as a barrier membrane on guided bone regeneration (GBR) in comparison with those of the resorbable collagen membranes. MATERIALS AND METHODS: BC membranes were fabricated using biomimetic technology. Surface properties were analyzed, Mechanical properties were measured, in vitro cell proliferation test were performed with NIH3T3 cells and in vivo study were performed with rat calvarial defect and histomorphometric analysis was done. The Mann-Whitney U test and the Wilcoxon signed rank test was used (alpha<.05). RESULTS: BC membrane showed significantly higher mechanical properties such as wet tensile strength than collagen membrane and represented a three-dimensional multilayered structure cross-linked by nano-fibers with 60 % porosity. In vitro study, cell adhesion and proliferation were observed on BC membrane. However, morphology of the cells was found to be less differentiated, and the cell proliferation rate was lower than those of the cells on collagen membrane. In vivo study, the grafted BC membrane did not induce inflammatory response, and maintained adequate space for bone regeneration. An amount of new bone formation in defect region loaded with BC membrane was significantly similar to that of collagen membrane application. CONCLUSION: BC membrane has potential to be used as a barrier membrane, and efficacy of the membrane on GBR is comparable to that of collagen membrane. PMID- 26816581 TI - Erratum: The effect of various sandblasting conditions on surface changes of dental zirconia and shear bond strength between zirconia core and indirect composite resin. AB - [This corrects the article on p. 214 in vol. 7, PMID: 26140173.]. PMID- 26816580 TI - Effect of microgrooves and fibronectin conjugation on the osteoblast marker gene expression and differentiation. AB - PURPOSE: To determine the effect of fibronectin (FN)-conjugated, microgrooved titanium (Ti) on osteoblast differentiation and gene expression in human bone marrow-derived mesenchymal stem cells (MSCs). MATERIALS AND METHODS: Photolithography was used to fabricate the microgrooved Ti, and amine functionalization (silanization) was used to immobilize fibronectin on the titanium surfaces. Osteoblast differentiation and osteoblast marker gene expression were analyzed by means of alkaline phosphatase activity assay, extracellular calcium deposition assay, and quantitative real-time PCR. RESULTS: The conjugation of fibronectin on Ti significantly increased osteoblast differentiation in MSCs compared with non-conjugated Ti substrates. On the extracellular calcium deposition assays of MSCs at 21 days, an approximately two fold increase in calcium concentration was observed on the etched 60-um-wide/10 um-deep microgrooved surface with fibronectin (E60/10FN) compared with the same surface without fibronectin (E60/10), and a more than four-fold increase in calcium concentration was observed on E60/10FN compared with the non-etched control (NE0) and etched control (E0) surfaces. Through a series of analyses to determine the expression of osteoblast marker genes, a significant increase in all the marker genes except type I collagen alpha1 mRNA was seen with E60/10FN more than with any of the other groups, as compared with NE0. CONCLUSION: The FN conjugated, microgrooved Ti substrate can provide an effective surface to promote osteoblast differentiation and osteoblast marker gene expression in MSCs. PMID- 26816582 TI - The Impact of Remote Ischemic Pre-Conditioning on Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography and Angioplasty: A Double-Blind Randomized Clinical Trial. AB - BACKGROUND AND OBJECTIVE: Contrast-induced nephropathy (CIN) is an acute major complication following intravascular administration of iodinated contrast agents; however, the best approach for preventing CIN is not clear. Remote ischemic pre conditioning (RIPC) is a new, non-pharmacological method that has been considered for the prevention of CIN following coronary angiography. This study assessed the effects of RIPC with four brief episodes of upper limb ischemia and reperfusion in the prevention of contrast-induced nephropathy (CIN) after coronary angiography and/or angioplasty. METHODS: In this double-blind randomized clinical trial, we enrolled 51 patients with chronic stable angina and non-ST elevation acute coronary syndrome (NSTE.ACS), and they underwent coronary angiography and/or angioplasty. Standard fluid therapy with normal saline was prescribed for all patients before and after the procedure. The patients were divided into two groups, i.e., a study group of patients who had undergone RIPC intervention and a control group of patients who had not undergone RIPC. One hour before the procedure, a sphygmomanometer cuff was placed around one arm and inflated up to 50 mmHg above the systolic pressure for five minutes; then, the cuff was deflated for another five minutes, and this cycle was repeated four times. The patients' serum creatinine levels were measured at baseline and 48 hours after the procedure, and the incidence of CIN was calculated. RESULTS: Twenty-one males and 30 females were studied in two groups, i.e., an RIPC intervention group (n = 25) and a control group (n = 26) that were homogenous considering baseline characteristics. No significant difference was observed in the mean level of serum creatinine between the two groups at a post-intervention time of 48 hours (RICP: 1.74 +/- 0.70 mg/dL vs. CONTROL: 1.75 +/- 0.87 mg/dL; P = 0.64). However, a lower incidence rate of CIN was observed 48 hours after the administration of the contrast medium in the RIPC group, but it was not statistically significant (RIPC: 23.1% vs. CONTROL: 12.0%; P = 0.30). CONCLUSION: It seems that adequate fluid therapy is still the most effective strategy for preventing CIN and that RIPC might have additional protective effects in very high risk patients, such as those with severe renal insufficiency and heart failure. PMID- 26816583 TI - Coping response following a diagnosis of breast cancer: A systematic review. AB - INTRODUCTION: Coping with breast cancer is an important health issue that results in adjustments to the disease in survivors. The present systematic review aims to synthesize the evidence about the coping strategies used by women who are primary breast cancer survivors to adjust to their new situations in their lives. METHODS: Searches were conducted using Google Scholar, PubMed, Scopus, Wiley Online Library, and PsycINFO, using the terms "breast cancer," "breast malignancy," "coping strategies," "coping behaviors," and "adjustment" from January 2000 to July 2015. Only relevant studies in English were selected at the end of the search. Only those papers were selected that focused on coping strategies/behaviors that were used by breast cancer survivors. RESULTS: Searching the electronic databases resulted in 2390 articles. Ultimately, 20 studies met the inclusion criteria of the present study and were included in the review. Two reviewers independently reviewed all relevant articles using the same inclusion criteria. The reviewers completed a quality assessment using the Newcastle-Ottawa Quality Assessment scales for observational studies. The more frequent coping strategies that patients with breast cancer used in the studies were 1) seeking social support (9 studies), 2) positive reframing and reappraisal behaviors as problem focused strategies (7 studies), 3) religious/spirituality focused efforts (8 studies), 4) emotional expression as positive emotion-focused strategies (3 studies), and 5) avoidance and distraction as avoidance orientated strategies (6 studies). Women with different ethnicities and educational levels used different coping strategies with breast cancer, and they used different strategies in different phases of the disease. CONCLUSION: This systematic review revealed that seeking social support and emotion-focused efforts were the main coping strategies that women with breast cancer diagnosis used, especially in the early phase of breast cancer diagnosis. This information about the coping responses of patients may be useful in designing interventional programs to assist other women in dealing with the various challenges imposed upon them by their illness. PMID- 26816584 TI - Macro determinants of Iranian provincial healthcare expenditures from 2006 to 2013: evidence from panel data. AB - INTRODUCTION: During the last few decades, healthcare expenditures (HCEs) have increased significantly in Iran and throughout the world. Understanding the determinants of such increases is essential to health policymakers in finding the best policies to manage healthcare costs. This study aimed to determine the impact of some of the key explanatory variables on household healthcare expenditures across the provinces of Iran. METHODS: A panel data econometric model was used to determine the main factors that affected household healthcare expenditures (HHCEs) across the provinces of Iran from March 21, 2006 to February 19, 2013. The data on household healthcare expenditures per capita, number of physicians per 10,000 population, the degree of urbanization, the proportion of the population that was 65 or older, household income per capita, and literacy rate were obtained from the Household Expenditure and Income Survey (HEIS) data in the Statistical Center of Iran. F-Limer and Hausman tests were used to choose the panel data, and Stata V.12 was used to analyze the data. RESULTS: Our findings indicated that income per capita, physicians per 10,000 population, and the degree of urbanization had significant impacts on healthcare expenditures. Also, the results of the study showed the elasticity of income, physicians, urbanization, proportion of the population 65 or older, and the literacy rate were 0.25 (p < 0.002), 0.37 (p < 0.001), 5.01 (p < 0.001), -0.1 (p < 0.73), and 1.02 (p < 0.082), respectively. CONCLUSION: The results of the study indicated that the income elasticity of healthcare expenditures was less than 1; health expenditures were considered to be a "necessity good" across the provinces of Iran during the period that was studied. In addition, there were some other factors that affected healthcare expenditures that were not considered in the study, such as the advancement of new technology and the costs of dying. However, it is recommended that future research examine the effect of these factors on HCEs in Iran. PMID- 26816585 TI - Would Phoenix Dactyflera Pollen (palm seed) be considered as a treatment agent against Males' infertility? A systematic review. AB - INTRODUCTION: Oxidative stress is a key factor involved in male infertility, which is due to an unnatural increase in environmental free radicals. In the majority of cases, this has a negative effect on a male's ability to impregnate a female. Currently, it is believed that spermatozoa can be protected against the damages induced by oxidative stress by saturating sperm with antioxidants. The antioxidant role of phoenix dactylifera pollen is capable of collecting the reactive oxygen and neutralizing it in and out of body cells. The present research provides a review of the antioxidant roles of phoenix dactylifera pollen on male infertility. METHODS: This research is based on English-Language studies and articles found by comprehensively reviewing electronic databases, websites, books, and academic articles over the last 10 years. RESULTS: The phenolic compounds of phoenix dactylifera pollen, due to the existing polyphenols, are strong chelators of heavy metals. Therefore, they are effective in eliminating environmental hydroxyl radicals. Moreover, these plants have high capacities of eliminating hydroxyl free radicals, picrylhydrazyl, diphenyl and phoenix dactylifera pollen and also inhibiting glutathione-S-transferase (GST). CONCLUSION: Currently, the use of herbal antioxidants to neutralize reactive oxygen species (ROS) and reduce the negative effects of oxidative stress on body cells and tissues has attracted researchers' attention. Various substances, such as flavonoids and catechins, perform their antioxidant role by increasing the concentration of glutathione peroxidase. The final product of this process is an increase in the number of motile sperm, which can have significant effects on fertility. PMID- 26816586 TI - Organizational Climate and Work Addiction in Shahid Sadoughi University of Medical Sciences, 2014: a Case Study. AB - INTRODUCTION: The occupational nature of employees in headquarters units of the University requires them to deal with support issues. Thus, there is some pressure on these employees to complete their assignments on time so that employees in the line units can accurately and expeditiously perform their duties. As a result, work addiction behaviors are sometimes observed among the headquarters personnel. Considering the importance of work addiction and recognizing the factors that intensify it, this study investigated the relationship between organizational climate and the work addiction of headquarters personnel at the Shahid Sadoughi University of Medical Sciences. METHODS: This descriptive-analytic study was conducted using stratified random sampling of 151 University employees in 2014. The data collection tool was an organizational climate questionnaire, which was supplemented by the Work Addiction Risk Test (WART). The data were analyzed using the Pearson test, Spearman test, independent t-test, Mann-Whitney test, one-way analysis of variance (ANOVA), and the Kruskal-Wallis test using IBM-SPSS version 20. RESULTS: The findings of this study showed that the organizational climate was at a moderate level, and employees were in the danger level in terms of work addiction. In addition, among the dimensions of organizational climate, the risk dimension had a significant relationship with work addiction (p<0.05), and the dimensions of structure and responsibility were significantly different from occupational group and monthly salary (p<0.05). Single employees showed a significant difference from married employees in the two dimensions of criteria and conflict (p<0.05). CONCLUSION: Since the organizational climate score was low and the work addiction score was at the high-risk level, this issue demands more attention of senior managers and human resource officers of organizations to improve the organizational climate and increase employees' awareness of work addiction. PMID- 26816587 TI - Accuracy of universal polymerase chain reaction (PCR) for detection of bacterial meningitis among suspected patients. AB - INTRODUCTION: Central nervous system (CNS) infections are life-threatening diseases caused by viral, bacterial, parasitic and fungal microorganisms. The aim of this study was to determine the accuracy of universal polymerase chain reaction (PCR) for the detection of bacterial meningitis among patients who were referred to Koodakan Hospital in Bandar Abbas because they were suspected of having the disease. METHODS: This study was conducted in 2013 on the patients who were admitted to Bandar Abbas' Koodakan Hospital because they were suspected of having meningitis. A questionnaire, including demographic data, was completed for each patient. Universal PCR, Cerebrospinal fluid (CSF) analysis, and gram staining and cultures were done for all the patients. The data were analyzed using SPSS software. RESULTS: Among the 100 patients studied 59 (59%) were male and 41 (41%) were female. No patient in our study had a positive smear and culture for meningitis. Among the patients with negative smears and cultures six (6%) had positive universal PCR, and 94 (94%) had negative universal PCR. Based on these results, PCR had 95% specificity and 100% negative predictive value for the prediction of meningitis. In 30 patients (30%), the biochemical analysis of CSF were in favor of meningitis. Among the 30 patients, six patients (20%) had positive universal PCR and 24 patients (80%) had negative universal PCR. CONCLUSION: Based on our results, the universal PCR test is useful in the diagnosis of bacterial meningitis in children. We recommend using it in combination with other tests, such as CSF analysis, for diagnosis of bacterial meningitis. PMID- 26816588 TI - Role of alteration in Treg/Th17 cells' balance in nephropathic patients with Type 2 diabetes mellitus. AB - INTRODUCTION: In type 2 diabetes mellitus, the adaptive immune system drives systemic inflammation, promoting insulin resistance and related complications, such as diabetic nephropathy. Increased infiltration of activated T lymphocytes has been found in patients with diabetic nephropathy. T-cell influx and accumulation are the factors that aggravate diabetic nephropathy and link with glomerular filtration surface and albumin excretion. An appropriate balance between pro-inflammatory (T helper 17: Th17, and T helper 1: Th1) and anti inflammatory (regulatory T cells: Tregs) subsets of T cells is critical to maintain homeostasis and avoid inflammatory disease. The aim of this study was to determine the balance between T helper 17 and regulatory T cells in type 2 diabetic patients who have diabetic nephropathy. METHODS: This case control study was conducted between December 2013 and June 2014 in Theodor Bilharz Research Institute in Egypt. Forty patients and 20 healthy volunteers were recruited in the study, and three groups were formed, i.e. two groups of cases with 20 patients in each group and one group of 20 controls) The groups were 1) 20 type 2 diabetic patients with nephropathy (group A); 2) 20 type 2 diabetic patients without nephropathy (group B); and 3) 20 healthy individuals (control group). Evaluation of T cells was done by standard 2-color flow cytometry. RESULTS: The study found higher mean of Th17 counts and Th17/Treg ratio among type 2 diabetic nephropathy patients compared to other groups; but a lower mean of Treg count was identified among type 2 diabetic nephropathy patients than in the other groups (p value = 0.001). CONCLUSION: The important role for regulatory T cells in the protection against nephropathy in type 2 diabetic patients was demonstrated, and also it was observed that T helper 17 cells were associated with renal affection. PMID- 26816589 TI - Occult Hepatitis C Virus Infection in Hemodialysis Patients; Single Center Study. AB - INTRODUCTION: A new form of hepatitis C virus infection, known as occult hepatitis C virus (HCV) infection, is characterized by the presence of HCV_RNA in the liver or peripheral blood mononuclear cells (PBMCs). However, no serological markers of infection occur and there is not as much damage to the liver damage as is produced by chronic hepatitis C. There is a high incidence of HCV infection among hemodialysis patients, there is significant concern about viral transmission. HCV infection is a major problem in hemodialysis (HD) units even though blood products are screened for anti-HCV antibodies and other precautions are taken. The aim of this study was to determine the prevalence of occult HCV infection in PBMC in chronic hemodialysis (CHD) patients in the dialysis unit at Theodor Bilharz Research Institute (TBRI) with HCV antibodies and HCV RNA negativity irrespective of their liver function tests. METHODS: Fifty-three patients who were repeatedly were anti-HCV negative and serum HCV-RNA negative and on regular hemodialysis for > six months were enrolled in the study, which was conducted in the dialysis unit of Nephrology Department at TBRI; there were 10 healthy matched controls. The patients were classified into two groups according to the result HCV RNA in their PBMCs. Serological markers of HCV infection, including anti-HCV antibody and serum HCV-RNA, were repeatedly negative for all patients included in the study. We collected serum and PBMC samples from the patients on the day they entered the study. The test of all serum samples for anti-HCV antibodies and HCV-RNA was repeated by RT-PCR to ensure that the patients did not have these HCV serologic markers, We also measured their ALT and GGT levels. RESULTS: Occult hepatitis C virus infection (OCI) was detected in 15.1% of our CHD patients without any evidence of chronic liver disease. CONCLUSION: Occult HCV infection was present among the hemodialysis patients irrespective of whether they had persistent abnormal values of liver enzymes for which no cause had been identified. Further study is required to determine the clinical significance of occult HCV infections in these patients. PMID- 26816590 TI - Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma. AB - INTRODUCTION: Hepatitis C virus (HCV) is a major cause of chronic liver disease in Egypt, leading to hepatic fibrosis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Liver fibrosis is characterized by excessive deposition of extracellular matrix (ECM). Newly-recognized pathogenic mechanisms point to the epithelial-mesenchymal transition (EMT) of hepatocytes to matrix synthesizing (myo-) fibroblasts. Transforming growth factor-beta (TGF-beta1), bone morphogenic protein (BMP)-7, and connective tissue growth factor (CTGF) are biomarkers reflecting the EMT process. YKL-40 is a glycoprotein member of ECM and plays a role in cancer cell proliferation. The purpose of this study was to determine the serum biomarkers of EMT and its impact on the fibrogenic process and tumorigenesis in HCV-genotype 4 patients. METHODS: In this case-control study that was conducted in 2013-2014, 97 HCV-infected patients were subjected to clinical examination, laboratory investigations, and liver biopsy. According to the histopathologic examination, they were classified to F0 (14 cases), F1 (17 cases), F2 (15 cases), F3 (18 cases), F4 (22 cases), and HCC (11 cases). Fifteen age- and gender-matched subjects were included as normal controls. Serum levels of TGF-beta1, BMP-7, CTGF, YKL-40 were assessed, and the TGF-beta1/BMP-7 ratios were calculated. The data were analyzed by plotting the receiver operating characteristic curve (ROC), Pearson product-moment correlation coefficient, and Spearman's rank correlation coefficient (Spearman's rho). RESULTS: Serum levels of TGF-beta1, BMP-7, CTGF, and YKL-40 were significantly increased in all patient groups compared to controls (p < 0.001). LC exhibited the highest CTGF level and YKL-40 was highest in HCC. The TGF-beta1/ BMP-7 ratios reflected the progression of EMT from CHC to LC, however, there was no significant difference between LC and HCC. TGF-beta1/ BMP-7 ratio is considered to reflect positive correlation with CTGF in LC group (r = 0.629; p < 0.03) and YKL-40 in HCC group (r = 0.504; p < 0.04). CONCLUSION: Increased TGF-beta1/BMP-7 ratio and CTGF levels reflect the rate of EMT and provide information about fibrogenic activity. Also, this ratio, in association with YKL-40, can be used to predict malignant transformation in HCV-genotype 4 Egyptian patients. PMID- 26816591 TI - Effective Communication Barriers in Clinical Teaching among Malaysian Medical Students in Zagazig Faculty of Medicine (Egypt). AB - INTRODUCTION: effective communication in a clinical environment plays a vital role in patient assessment and treatment. The aim of this study was to understand the experiences of Malaysian medical students concerning communication barriers during clinical practice. The goal was to provide answers for three important research questions, i.e., 1) Are communication barriers an impediment to Malaysian students during clinical teaching? 2) What is the nature of the language barriers that the students encounter? and 3) What are the best ways of reducing these barriers during clinical teaching? METHODS: The qualitative method was used to conduct the research, and open-ended questionnaires were used to collect the data. The study was conducted on 95 fourth-, fifth-, and sixth-year students, 80% of whom completed the study. RESULTS: Medical students from Malaysia who have limited knowledge of the Arabic language experience some difficulties in communicating with staff members, patients, and nurses during their clinical practices. CONCLUSION: Successful orientation of students to the language used in the clinical environment will help the students overcome the communication barriers they encounter during their clinical practices. PMID- 26816592 TI - Total mesorectal excision for the treatment of rectal cancer. AB - INTRODUCTION: In the surgical treatment of rectal cancer, a clear circumferential resection margin and distal resection margin should be obtained. The aim of this study was to determine the morbidity, mortality, survival outcome, and local failure after total mesorectal excision (TME) in the surgical treatment of rectal cancer. METHODS: This retrospective study was conducted on 101 patients treated for rectal cancer using low anterior resection (LAR), abdominoperinial resection (APR), or Hartmaan's technique. In all operative procedures, total mesorectal excisions (TMEs) were done. The patients were treated from November 2000 to April 2011 in the South Egypt Cancer Institute (SECI) of Assuit University (Egypt). Neo adjuvant therapy was given to those patients with serosalin filtration, lymph node involvement, and sexual and urinary function impairment. Data were analyzed using IBM-SPSS version 21, and survival rates were estimated using the Kaplan Meier method. RESULTS: One hundred one patients were evaluable (61 males, 40 females). Regarding the operative procedure used, it was: (APR), LAR, Hartmaan's technique in 15.8%, 71.3%, and 12.9% of patients, respectively. Operation-related mortality during the 30 days after surgery was 3%. The operations resulted in morbidity in 25% of the patients, anastomotic site leak in 5.9% of the patients, urinary dysfynction in 9.9% of the patients, and erectile dysfunction in 15.8% of the male patients. Regarding safety margin, the median distances were distal/radial margin, 23/12 mm, distal limit 7 cm. Median lymph nodes harvest 19 nodes. Primary tumor locations were anteriorly 23.8%, laterally 13.9%, posteriorly 38.6%, and circumferential 23.8%. Protective stoma 16.8%. Primary Tumor TNM classification (T1, T2, T3, and T4; 3, 28.7, 55.4, and 12.9%, respectively). Nodes Metastases (N0, N1, and N2; 57.4, 31.7, and 10.9%, respectively). TNM staging (I, II, III, and IV; 15.8, 29.7, 46.5, and 7.9%, respectively). Chemotherapy was administered to 67.3% of the patients. Radiotherapy (short course neoadjuvant, long course neoadjuvant, and adjuvant postoperative used in 33.7, 20.8, and 19.8% of patients, respectively). Survival 5-years CSS was 73% and 5-years RFS 71%. Mean operative time was 213 minutes. The average amount of intraoperative blood loss was 344 mL. CONCLUSION: Total mesorectal excision (TME) represents the gold-standard technique in rectal cancer surgery. It is safe with neoadjuvent chemoradiotherapy and provides both maximal oncological efficiency (local control and long-term survival and maintenance of a good quality of life). PMID- 26816593 TI - Cognitive Behavioral Development in Children Following Maternal Postpartum Depression: A Review Article. AB - Mothers' constitute is a very important part of infants' social environment and mediate their experience with the surrounding world. Postpartum depression, which is considered one of the most common and important psychiatric disorders, affects 10-15% of mothers, its causes are different. By investigating various sources, some effects of this disorder have been observed on the cognitive development of children, particularly among boys, such as language, intelligence quotient (IQ), and behavioral problems. Thus, it is imperative to study the effects of postpartum depression on children's growth and development and to identify methods of reducing these effects. This review indicates that postpartum depression in mothers reduces children's cognitive performance. The adverse effects of postpartum depression on children's development seem to be mediated by the mother's interpersonal behavior and the infant gender. The review of previous studies shows that postpartum depression reduces children's cognitive performance by impairing maternal mental and behavioral care. PMID- 26816594 TI - IL10 in Lupus Nephritis: Detection and relationship with disease activity. AB - INTRODUCTION: Glomerulonephritis is a major determinant of the course and prognosis of systemic lupus erythematosus (SLE) and is evident in 40%-85% of patients. IL10, a cytokine produced by monocytes and-to a lesser extent lymphocytes, has pleiotropic effects in immune regulation and inflammation. It enhances B cell survival, proliferation, differentiation, and antibody production; these effects play a role in autoimmune diseases. Among identified polymorphisms in the IL10 promoter, three linked single nucleotide polymorphisms (SNPs) of -1082 G/A, 819 T/C, and -592 A/C have been shown to influence the IL10 gene expression. Compared with the -592 C allele, the 592 A is associated with lower IL10 production in vitro. The objectives of this study were to investigate the -592 A/C polymorphism in patients with and without lupus nephritis and to assess its influence on IL10 secretion in vivo and its role in pathogenesis and clinicopathological characteristics of lupus nephritis. METHODS: This case control study was conducted on 40 SLE patients recruited for the study from those attending the nephrology department of the Theodor Bilharz Research Institute (outpatient clinic and inpatient ward) in 2013. Patients were divided into two groups, group I (SLE patients without evidence of nephritis) and group II (SLE patients with lupus nephritis). Data were analyzed using SPSS (version 12), a t test, Chi square, ANOVA, and the Pearson product-moment correlation coefficient. RESULTS: Our study found an increase in IL10 serum in lupus nephritis patients compared to those without renal involvement (without statistical significance). No significant differences emerged in the level of IL10 serum among different pathological classes. CONCLUSION: The IL10 gene (-592 A/C) polymorphism, though not associated with lupus nephritis's susceptibility in the present study, does play a role. PMID- 26816595 TI - Like a snail, our journal (JDI) makes slow, but steady, progress. PMID- 26816597 TI - A novel role for the cell cycle regulatory complex cyclin D1-CDK4 in gluconeogenesis. AB - Dysregulation of gluconeogenesis is a key pathological feature of type 2 diabetes. However, the molecular mechanisms underlying the regulation of gluconeogenesis remain unclear. Bhalla et al. recently reported that cyclin D1 suppresses hepatic gluconeogenesis through CDK4-dependent phosphorylation of PGC1alpha and consequent inhibition of its activity. The cyclin D1-CDK4 might thus serve as an important link between the cell cycle and control of energy metabolism through modulation of PGC1alpha activity. PMID- 26816596 TI - Potentials of incretin-based therapies in dementia and stroke in type 2 diabetes mellitus. AB - Patients with type 2 diabetes mellitus are at risk for accelerated cognitive decline and dementia. Furthermore, their risk of stroke is increased and their outcome after stroke is worse than in those without diabetes. Incretin-based therapies are a class of antidiabetic agents that are of interest in relation to these cerebral complications of diabetes. Two classes of incretin-based therapies are currently available: the glucagon-like-peptide-1 agonists and the dipeptidyl peptidase-4 -inhibitors. Independent of their glucose-lowering effects, incretin based therapies might also have direct or indirect beneficial effects on the brain. In the present review, we discuss the potential of incretin-based therapies in relation to dementia, in particular Alzheimer's disease, and stroke in patients with type 2 diabetes. Experimental studies on Alzheimer's disease have found beneficial effects of incretin-based therapies on cognition, synaptic plasticity and metabolism of amyloid-beta and microtubule-associated protein tau. Preclinical studies on incretin-based therapies in stroke have shown an improved functional outcome, a reduction of infarct volume as well as neuroprotective and neurotrophic properties. Both with regard to the treatment of Alzheimer's disease, and with regard to prevention and treatment of stroke, randomized controlled trials in patients with or without diabetes are underway. In conclusion, experimental studies show promising results of incretin-based therapies at improving the outcome of Alzheimer's disease and stroke through glucose-independent pleiotropic effects on the brain. If these findings would indeed be confirmed in large clinical randomized controlled trials, this would have substantial impact. PMID- 26816598 TI - Renoprotective effects of incretin-based drugs: A novel pleiotropic effect of dipeptidyl peptidase-4 inhibitor. PMID- 26816599 TI - Important role of 5-hydroxytryptamine in glucocorticoid-induced insulin resistance in liver and intra-abdominal adipose tissue of rats. AB - AIM/INTRODUCTION: Both glucocorticoids and 5-hydroxytryptamine (5-HT) have been shown to induce insulin resistance (IR) in hepatocytes and adipocytes. Here, we explore whether there is a correlation between them. MATERIALS AND METHODS: Except for the control group, male rats were exposed to dexamethasone treated with or without para-chlorophenylalanine (pCPA), or carbidopa for 20 days. Except for the control group, buffalo rat liver 3A (BRL-3A) cells were exposed to dexamethasone for 24 h, treated with or without pCPA, carbidopa, or clorgiline for 48 h, or exposed to 5-HT treated with or without fluoxetine for 48 h. Whole body IR was determined by both glucose tolerance test and measurement of fasting blood glucose and insulin, whereas hepatocytes or adipocytes IR was determined by examining either hepatic gluconeogenesis, steatosis and glucose transporter 2 expression or lipolysis. RESULTS: Dexamethasone-induced whole-body IR, liver and intraabdominal adipose IR were accompanied by upregulated expressions of tryptophan hydroxylase-1 and aromatic amino acid decarboxylase with increased 5 HT level in both tissues, which were attenuated significantly by pCPA, inhibiting tryptophan hydroxylase-1, or carbidopa, inhibiting aromatic amino acid decarboxylase. [Correction added on 22 September 2015, after first online publication: 'inhibiting aromatic amino acid decarboxylase' was duplicated and has been replaced by 'tryptophan hydroxylase-1'.] In the BRL-3A cells, dexamethasone-induced IR was also accompanied by upregulated 5-HT synthesis in dose- and time-dependent manners, and was attenuated by pCPA or carbidopa, but exacerbated by clorgiline, inhibiting monoamine oxidase-A to further increase 5 HT level. Dexamethasone also enhanced 5-HT 2A and 2B receptor expressions in both tissues and BRL-3A cells. Additionally, blocking 5-HT transporter with fluoxetine significantly suppressed 5-HT-induced IR in BRL-3A cells. CONCLUSION: Enhancement of 5-HT synthesis in liver and intra-abdominal adipose is an important reason for glucocorticoids-induced IR. PMID- 26816600 TI - Lack of association between anemia and renal disease progression in Chinese patients with type 2 diabetes. AB - AIMS/INTRODUCTION: Anemia has a close interaction with renal dysfunction in diabetes patients. More proof is still awaited on the relationship between anemia and the progression of renal disease in this population. MATERIALS AND METHODS: In the present longitudinal study, 1,645 Chinese type 2 diabetes patients without end-stage renal disease were included in the analysis in Nanjing, China, during January 2006 and December 2012. All patients were managed by staged diabetes management protocol, and clinical parameters were collected at each visit. The end-point of progression of renal disease was evaluated during the follow up. Cox regression analysis was used to estimate the risk of anemia on renal disease progression. RESULTS: On recruitment, 350 (21.3%) patients had anemia, which was more common among those with older ages, longer diabetes duration, lower estimated glomerular filtration rate or more albuminura. On median follow up of 49 months (range 28-62 months), 37 patients (2.2%) developed the defined renal end-point. Compared with those without anemia, patients with anemia had a higher risk of renal disease progression. However, multivariate analysis showed that anemia lost its statistical significance once estimated glomerular filtration rate was added into the model. Although the incidence of renal disease progression markedly increased by anemia status in patients of estimated glomerular filtration rate <60 mL/min/1.73 m(2), anemia was still not an independent risk factor for renal disease progression in this subgroup. CONCLUSIONS: Anemia was a common finding in Chinese type 2 diabetes patients. Anemia was a risk factor for renal disease progression, but lost its significance once baseline renal function was adjusted. PMID- 26816601 TI - Association between glycemic control and birthweight with glycated albumin in Chinese women with gestational diabetes mellitus. AB - AIMS/INTRODUCTION: To assess glycated albumin (GA) as a potential glycemic index in managing gestational diabetes mellitus (GDM). MATERIALS AND METHODS: Eligible pregnant women were divided into the GDM group with abnormal result on a 75-g oral glucose tolerance test (OGTT) and the control (normal) group. GA measurements, Pearson's correlation analysis, multiple logistic regression and receiver operating characteristic curve analysis were obtained at the follow-up examination of participants in the two groups. RESULTS: A total of 2,118 women were assigned to the GDM group (n = 639) and control group (n = 1,479). The mean level of serum GA in GDM group was significantly greater than that in the control group at both 24-28 and 36-38 weeks of gestation (P < 0.05). The area under the receiver operating characteristic curve for GA defining good glycemic control in GDM was 0.874 (95% confidence interval 0.811-0.938). The cut-off point for the GA levels derived from the receiver operating characteristic curve was 11.60%, which had sensitivity and specificity for detecting a poor glycemic status of 75.93% and 86.36%, respectively. The risk of birthweight >=3,500 g and macrosomia increased significantly with GA levels >=13.00% at 24-28 weeks and >=12.00% at 36 38 weeks of gestation. CONCLUSIONS: GA might be an appropriate and conveniently measured index that can detect poor glycemic control and predict birthweights in GDM women. PMID- 26816602 TI - Higher intake of fruits, vegetables or their fiber reduces the risk of type 2 diabetes: A meta-analysis. AB - AIMS/INTRODUCTION: Some previous studies reported no significant association of consuming fruit or vegetables, or fruit and vegetables combined, with type 2 diabetes. Others reported that only a greater intake of green leafy vegetables reduced the risk of type 2 diabetes. To further investigate the relationship between them, we carried out a meta-analysis to estimate the independent effects of the intake of fruit, vegetables and fiber on the risk of type 2 diabetes. MATERIALS AND METHODS: Searches of MEDLINE and EMBASE for reports of prospective cohort studies published from 1 January 1966 to 21 July 2014 were carried out, checking reference lists, hand-searching journals and contacting experts. RESULTS: The primary analysis included a total of 23 (11 + 12) articles. The pooled maximum-adjusted relative risk of type 2 diabetes for the highest intake vs the lowest intake were 0.91 (95% confidence interval [CI] 0.87-0.96) for total fruits, 0.75 (95% CI 0.66-0.84) for blueberries, 0.87 (95% CI 0.81-0.93) for green leafy vegetables, 0.72 (95% CI 0.57-0.90) for yellow vegetables, 0.82 (95% CI 0.67-0.99) for cruciferous vegetables and 0.93 (95% CI 0.88-0.99) for fruit fiber in these high-quality studies in which scores were seven or greater, and 0.87 (95% CI 0.80-0.94) for vegetable fiber in studies with a follow-up period of 10 years or more. CONCLUSIONS: A higher intake of fruit, especially berries, and green leafy vegetables, yellow vegetables, cruciferous vegetables or their fiber is associated with a lower risk of type 2 diabetes. PMID- 26816603 TI - Metabolic parameters in type 2 diabetic patients with varying degrees of glycemic control during Ramadan: An observational study. AB - AIMS/INTRODUCTION: The changes in metabolic parameters in type 2 diabetic patients who fast during Ramadan have not been studied in Singapore. This study aimed to examine the trends of glycated hemoglobin (HbA1c), systolic blood pressure, low-density lipoprotein cholesterol, and triglycerides in diabetic patients with varying degrees of glycemic control and different types of therapeutic approaches during Ramadan. METHODS: The present retrospective study used a national electronic database to examine the metabolic parameter of Malay patients with type 2 diabetes. Eligible patients were stratified into three groups based on their mean HbA1c control before Ramadan: group 1 (HbA1c >=10%), group 2 (HbA1c 7.1-9.9%) and group 3 (HbA1c <=7%). Patients with a glomerular filtration rate <15 mL/min were excluded. The trends of metabolic parameters were traced before, during and after Ramadan. RESULTS: Of 13,565 patients examined, 5,172 patients (38.1%) were eligible for this study. Mean change of HbA1c varied from -1.4% to +0.2% during Ramadan, with the greatest reduction observed in group 1 (P < 0.001). A minimal systolic blood pressure reduction was observed in groups 2 and 3 (2 mmHg; P < 0.01). Low-density lipoprotein cholesterol and triglycerides changes were insignificant. A small, 0.1%, reduction in mean HbA1c was observed in patients taking oral antidiabetic agents during Ramadan (P < 0.001). CONCLUSIONS: Blood glucose was most affected during Ramadan, particularly in patients with mean baseline HbA1c >=10%. The type of antidiabetic agent used did not seem to contribute to glycemic changes. PMID- 26816604 TI - Liraglutide is effective and well tolerated in combination with an oral antidiabetic drug in Japanese patients with type 2 diabetes: A randomized, 52 week, open-label, parallel-group trial. AB - INTRODUCTION: The safety and efficacy of liraglutide in combination with an oral antidiabetic drug (OAD) compared with combination of two OADs were assessed in Japanese patients with type 2 diabetes. MATERIALS AND METHODS: This was a 52 week, open-label, parallel-group trial in which patients whose type 2 diabetes was inadequately controlled with a single OAD (glinide, metformin, alpha glucosidase inhibitor or thiazolidinedione) were randomized 2:1 to either pretrial OAD in combination with liraglutide 0.9 mg/day (liraglutide group; n = 240) or pretrial OAD in combination with an additional OAD (additional OAD group; n = 120). The primary outcome measure was the incidence of adverse events (AEs). RESULTS: Overall, 86.3% of patients in the liraglutide group and 85.0% of patients in the additional OAD group experienced AEs; these were similar in nature and severity. Adverse event rates were 361 and 331 per 100 patient-years of exposure, respectively. Confirmed hypoglycemia was rare (seven episodes in two patients on liraglutide, and two in two patients on additional OAD). There were no reported pancreatitis events, and no unexpected safety signals were identified. Mean reductions in glycosylated hemoglobin were significantly greater in the liraglutide group than the additional OAD group [estimated mean treatment difference -0.27% (95% confidence interval (CI) -0.44, -0.09; P = 0.0026)]; reductions in mean fasting plasma glucose levels were also greater with liraglutide [estimated mean difference -5.47 mg/dL (-0.30 mmol/L; 95% CI: -10.83, -0.10; P = 0.0458)]. CONCLUSIONS: Liraglutide was well tolerated and effective as combination therapy with an OAD in Japanese patients with type 2 diabetes. PMID- 26816605 TI - Subject-driven titration of biphasic insulin aspart 30 twice daily is non inferior to investigator-driven titration in Chinese patients with type 2 diabetes inadequately controlled with premixed human insulin: A randomized, open label, parallel-group, multicenter trial. AB - AIMS/INTRODUCTION: The present study was to compare the efficacy and safety of subject-driven and investigator-driven titration of biphasic insulin aspart 30 (BIAsp 30) twice daily (BID). MATERIALS AND METHODS: In this 20-week, randomized, open-label, two-group parallel, multicenter trial, Chinese patients with type 2 diabetes inadequately controlled by premixed/self-mixed human insulin were randomized 1:1 to subject-driven or investigator-driven titration of BIAsp 30 BID, in combination with metformin and/or alpha-glucosidase inhibitors. Dose adjustment was decided by patients in the subject-driven group after training, and by investigators in the investigator-driven group. RESULTS: Eligible adults (n = 344) were randomized in the study. The estimated glycated hemoglobin (HbA1c) reduction was 14.5 mmol/mol (1.33%) in the subject-driven group and 14.3 mmol/mol (1.31%) in the investigator-driven group. Non-inferiority of subject-titration vs investigator-titration in reducing HbA1c was confirmed, with estimated treatment difference -0.26 mmol/mol (95% confidence interval -2.05, 1.53) (-0.02%, 95% confidence interval -0.19, 0.14). Fasting plasma glucose, postprandial glucose increment and self-measured plasma glucose were improved in both groups without statistically significant differences. One severe hypoglycemic event was experienced by one subject in each group. A similar rate of nocturnal hypoglycemia (events/patient-year) was reported in the subject-driven (1.10) and investigator-driven (1.32) groups. There were 64.5 and 58.1% patients achieving HbA1c <53.0 mmol/mol (7.0%), and 51.2 and 45.9% patients achieving the HbA1c target without confirmed hypoglycemia throughout the trial in the subject-driven and investigator-driven groups, respectively. CONCLUSIONS: Subject-titration of BIAsp 30 BID was as efficacious and well-tolerated as investigator-titration. The present study supported patients to self-titrate BIAsp 30 BID under physicians' supervision. PMID- 26816606 TI - Efficacy and safety of insulin degludec in Japanese patients with type 1 and type 2 diabetes: 24-week results from the observational study in routine clinical practice. AB - This is first observational prospective study of insulin degludec in routine clinical practice that we evaluated the effect on glycemic control and risk of hypoglycemia in basal-bolus insulin therapy. We found that insulin degludec can maintain glycemic control at a lower insulin dose and frequency of hypoglycemia in type 1 diabetes, while it can improve glycemic control at equally insulin dose in type 2 diabetes. These results mean that insulin degludec is of use in routine clinical practice. PMID- 26816608 TI - Circulating cell-free mitochondrial deoxyribonucleic acid is increased in coronary heart disease patients with diabetes mellitus. AB - AIMS/INTRODUCTION: Circulating cell-free mitochondrial deoxyribonucleic acid (ccf mtDNA) is presumably derived from injured tissues or cells in the body and has been suggested to be potential biomarker in several diseases. The present study explored whether mtDNA could be used as a biomarker to evaluate disease in coronary heart disease (CHD) patients with or without diabetes mellitus (DM). MATERIALS AND METHODS: A total of 50 CHD patients with type 2 diabetes, 50 CHD patients without type 2 diabetes, and 50 age- and sex-matched patients without CHD and DM (non-CHD-DM) were recruited. Ccf-mtDNA levels were assessed by measuring the nicotinamide adenine dinucleotide dehydrogenase 1 gene using quantitative real-time polymerase chain reaction. Receiver operating characteristic curve analysis of plasma mtDNA in CHD with or without DM was also determined. Multivariate logistic regression analyses were carried out to determine the correlation between the mtDNA levels and traditional CHD risk factors. RESULTS: The plasma ccf-mtDNA levels were significantly elevated in CHD patients with DM compared with those without and non-CHD-DM. The area under the receiver operating characteristic curves of mtDNA in CHD patients with DM vs non CHD-DM was 0.907%. Correlation analyses of the mtDNA levels and traditional CHD risk factors showed that the mtDNA levels were significantly correlated with fasting blood glucose in CHD patients with DM. CONCLUSIONS: Ccf-mtDNA levels can be used as a biomarker in CHD patients with DM. PMID- 26816607 TI - Efficacy and safety of 40 mg or 60 mg duloxetine in Japanese adults with diabetic neuropathic pain: Results from a randomized, 52-week, open-label study. AB - INTRODUCTION: To examine the long-term efficacy and safety of duloxetine in the treatment of Japanese patients with diabetic neuropathic pain, we carried out a 52-week, randomized, open-label extension of a 12-week, double-blind, placebo controlled study. MATERIALS AND METHODS: Japanese adults with diabetic neuropathic pain who completed the double-blind study were eligible for this long term study, carried out at 71 sites in Japan (March 2008 to March 2010). Participants (n = 258) were re-randomized (1:1) to 40 mg/day or 60 mg/day duloxetine. Pain (Brief Pain Inventory severity and interference), quality of life (Patient's Global Impression of Improvement), and safety (primary outcome; adverse events, vital signs, metabolic measures) were measured. RESULTS: Significant (P < 0.0001) and sustained improvements (change +/- standard deviation; n = 257) were observed in Brief Pain Inventory severity (average pain score -2.1 +/- 1.7). Improvements were also seen in Brief Pain Inventory interference (mean of subscores -0.96 +/- 1.52) and Patient's Global Impression of Improvement (-0.9 +/- 1.1) scores; these scores decreased significantly (P < 0.0001) during the long-term study. Frequently reported adverse events included somnolence (13.6%), constipation (13.2%) and nausea (10.5%). Increases were observed in plasma glucose, glycosylated hemoglobin and total cholesterol levels, and in bodyweight and heart rate; however, none of these were clinically meaningful. Overall, there were no clinically significant safety concerns. CONCLUSIONS: This is the first publication of a long-term study carried out in Asia with an entirely Japanese patient population to suggest that long-term duloxetine therapy for diabetic neuropathic pain is effective and has an acceptable safety profile. PMID- 26816609 TI - Diagnosis of more gestational diabetes lead to better pregnancy outcomes: Comparing the International Association of the Diabetes and Pregnancy Study Group criteria, and the Carpenter and Coustan criteria. AB - AIMS/INTRODUCTION: The International Association of the Diabetes and Pregnancy Study Group (IADPSG) criteria for gestational diabetes are associated with increased prevalence. However, it remains unknown if intervention for more women with gestational diabetes mellitus by the IADPSG criteria results in better pregnancy outcomes than adopting the Carpenter and Coustan (C&C) criteria in Asian populations. MATERIALS AND METHODS: This was a retrospective cohort study. A total of 1,840 women, 952 subjects by the IADPSG criteria and 888 subjects by the C&C criteria, who delivered singletons in 2011 in a single tertiary center, were included in the study. The same therapeutic interventions were offered to women with gestational diabetes mellitus by the two criteria. Maternal and neonatal outcomes were evaluated. RESULTS: Adopting the IADPSG criteria increased the prevalence of gestational diabetes mellitus diagnosis to 13.44%, compared with 2.59% by the C&C criteria. The diagnosis was made 3 weeks earlier by the IADPSG criteria (27 vs 30.5 weeks, P < 0.0001). Adopting the IADPSG criteria was associated with reduced risk of primary cesarean section (adjusted odds ratio 0.79, 95% confidence interval 0.63-0.998, P < 0.05) and having any one of the adverse fetal outcomes (adjusted odds ratio 0.79, 95% confidence interval 0.64 0.998, P < 0.05), including birthweight >90th percentile, jaundice, admission to neonatal intensive care unit, birth trauma, neonatal hypoglycemia and fetal death. CONCLUSIONS: Adopting the IADPSG criteria is associated with improved pregnancy outcomes, at the expense of increased prevalence of gestational diabetes mellitus diagnosis. PMID- 26816610 TI - Klebsiella pneumoniae thyroid abscess complicated with esophagitis in a woman with newly diagnosed diabetes mellitus: A case report. AB - The thyroid is resistant to infection because of the anatomical and physiological characteristics of the gland, and even though diabetes can induce a compromised immune system, thyroid infection disease is scarcely encountered in diabetic patients. Thyroid abscess formation in an asymptomatic diabetic patient is an even rarer entity. We present a case of a previously asymptomatic diabetic patient showing clinical symptoms of painful swelling in the anterior neck followed by progressing dysphagia, who was later diagnosed with thyroid abscess as a result of Klebsiella pneumoniae, complicated with esophagitis caused by the same microorganism. To our knowledge, this is the first reported case of asymptomatic diabetes being clinically diagnosed with thyroid abscess as the first sign. PMID- 26816611 TI - Osmotic demyelination syndrome complicating diabetes with anti-glutamic acid decarboxylase antibodies and Graves' disease: A case report. AB - ODS associated with hyperglycemia is rare, with few reports.Immune responses have been recently reported as a mechanism of ODS onset. In the present case, an autoimmune predisposition may have contributed to ODS pathogenesis. PMID- 26816612 TI - Cortical morphological markers in children with autism: a structural magnetic resonance imaging study of thickness, area, volume, and gyrification. AB - BACKGROUND: Individuals with autism spectrum disorder (ASD) have been characterized by altered cerebral cortical structures; however, the field has yet to identify consistent markers and prior studies have included mostly adolescents and adults. While there are multiple cortical morphological measures, including cortical thickness, surface area, cortical volume, and cortical gyrification, few single studies have examined all these measures. The current study analyzed all of the four measures and focused on pre-adolescent children with ASD. METHODS: We employed the FreeSurfer pipeline to examine surface-based morphometry in 60 high functioning boys with ASD (mean age = 8.35 years, range = 4-12 years) and 41 gender-, age-, and IQ-matched typically developing (TD) peers (mean age = 8.83 years), while testing for age-by-diagnosis interaction and between-group differences. RESULTS: During childhood and in specific regions, ASD participants exhibited a lack of normative age-related cortical thinning and volumetric reduction and an abnormal age-related increase in gyrification. Regarding surface area, ASD and TD exhibited statistically comparable age-related development during childhood. Across childhood, ASD relative to TD participants tended to have higher mean levels of gyrification in specific regions. Within ASD, those with higher Social Responsiveness Scale total raw scores tended to have greater age-related increase in gyrification in specific regions during childhood. CONCLUSIONS: ASD is characterized by cortical neuroanatomical abnormalities that are age-, measure-, statistical model-, and region-dependent. The current study is the first to examine the development of all four cortical measures in one of the largest pre-adolescent samples. Strikingly, Neurosynth-based quantitative reverse inference of the surviving clusters suggests that many of the regions identified above are related to social perception, language, self-referential, and action observation networks-those frequently found to be functionally altered in individuals with ASD. The comprehensive, multilevel analyses across a wide range of cortical measures help fill a knowledge gap and present a complex but rich picture of neuroanatomical developmental differences in children with ASD. PMID- 26816613 TI - Probing the nuclear import signal and nuclear transport molecular determinants of PRV ICP22. AB - BACKGROUND: Herpes simplex virus 1 (HSV-1) ICP22 is a multifunctional protein and important for HSV-1 replication. Pseudorabies virus (PRV) ICP22 (P-ICP22) is a homologue of HSV-1 ICP22 and is reported to be able to selectively modify the transcription of different kinetic classes of PRV genes, however, the subcellular localization, localization signal and molecular determinants for its transport to execute this function is less well understood. RESULTS: In this study, by utilizing live cells fluorescent microscopy, P-ICP22 fused to enhanced yellow fluorescent protein (EYFP) gene was transient expressed in live cells and shown to exhibit a predominantly nucleus localization in the absence of other viral proteins. By transfection of a series of P-ICP22 deletion mutants fused to EYFP, a bona fide nuclear localization signal (NLS) and its key amino acids (aa) of P ICP22 was, for the first time, determined and mapped to aa 41-60 (PASTPTPPKRGRYVVEHPEY) and aa 49-50 (KR), respectively. Besides, the P-ICP22 was demonstrated to be targeted to the nucleus via Ran-, importin alpha1-, and alpha7 mediated pathway. CONCLUSIONS: Our findings reported herein disclose the NLS and molecular mechanism for nuclear transport of P-ICP22, these results will uncover new avenues for depicting the biological roles of P-ICP22 during PRV infection. PMID- 26816614 TI - The binding specificity of Translocated in LipoSarcoma/FUsed in Sarcoma with lncRNA transcribed from the promoter region of cyclin D1. AB - BACKGROUND: Translocated in LipoSarcoma (TLS, also known as FUsed in Sarcoma) is an RNA/DNA binding protein whose mutation cause amyotrophic lateral sclerosis. In previous study, we demonstrated that TLS binds to long noncoding RNA, promoter associated ncRNA-D (pncRNA-D), transcribed from the 5' upstream region of cyclin D1 (CCND1), and inhibits the expression of CCND1. RESULTS: In order to elucidate the binding specificity between TLS and pncRNA-D, we divided pncRNA-D into seven fragments and examined the binding with full-length TLS, TLS-RGG2-zinc finger RGG3, and TLS-RGG3 by RNA pull down assay. As a result, TLS was able to bind to all the seven fragments, but the fragments containing reported recognition motifs (GGUG and GGU) tend to bind more solidly. The full-length TLS and TLS-RGG2-zinc finger-RGG3 showed a similar interaction with pncRNA-D, but the binding specificity of TLS-RGG3 was lower compared to the full-length TLS and TLS-RGG2 zinc finger-RGG3. Mutation in GGUG and GGU motifs dramatically decreased the binding, and unexpectedly, we could only detect weak interaction with the RNA sequence with stem loop structure. CONCLUSION: The binding of TLS and pncRNA-D was affected by the presence of GGUG and GGU sequences, and the C terminal domains of TLS function in the interaction with pncRNA-D. PMID- 26816615 TI - Knockdown of CLIC4 enhances ATP-induced HN4 cell apoptosis through mitochondrial and endoplasmic reticulum pathways. AB - BACKGROUND: Human head and neck squamous carcinoma is the 6th most prevalent carcinoma worldwide. Although many novel therapies have been developed, the clinical treatment for patients remains non-ideal. Chloride intracellular channel 4 (CLIC4), one of the seven members of the CLIC family, is a newly found Cl(-) channel that participates in various biological processes, including cellular apoptosis and differentiation. Accumulating evidence has revealed the significant role of CLIC4 in regulating the apoptosis of different cancer cells. Here, we investigated the functional role of CLIC4 in the apoptosis of HN4 cells, a human head and neck squamous carcinoma cell line. RESULTS: In the present study, we used immunohistochemical staining to demonstrate that the expression level of CLIC4 is elevated in the tissue of human oral squamous carcinoma compared with healthy human gingival tissue. Specific CLIC4 small interfering RNA was used to knockdown the expression of CLIC4. The results showed that knockdown of CLIC4 with or without 100 MUM adenosine triphosphate (ATP) treatment significantly increased the expression of Bax, active caspase 3, active caspase 4 and CHOP but suppressed Bcl-2 expression in HN4 cells. Moreover, the results from the TdT mediated dUTP nick end labeling assay indicated that CLIC4 knockdown induced a higher apoptotic rate in HN4 cells under the induction of ATP. In addition, knockdown of CLIC4 dramatically enhanced ATP-induced mitochondrial membrane depolarization in HN4 cells. Moreover, intracellular Ca(2+) measurement revealed that Ca(2+) release induced by ATP and thapsigargin, a Ca(2+)-ATPase inhibitor of the endoplasmic reticulum, was significantly enhanced by the suppression of CLIC4 in HN4 cells. CONCLUSIONS: Knockdown of CLIC4 enhanced ATP-induced apoptosis in HN4 cells. Both the pathways of mitochondria and endoplasmic reticulum stress were involved in CLIC4-mediated cell apoptosis. Based on our finding, CLIC4 may be a potential and valuable target for the clinical treatment of head and neck squamous carcinoma. PMID- 26816617 TI - Erratum to: The relationship between quality of sleep and night shift rotation interval. AB - [This corrects the article DOI: 10.1186/s40557-015-0084-x.]. PMID- 26816616 TI - Incidence and risk factors for food hypersensitivity in UK infants: results from a birth cohort study. AB - BACKGROUND: The prevalence of food hypersensitivity in the UK is still largely open to debate. Additionally its pathogenesis is also unclear although it is known that there are differing phenotypes. Determining its prevalence, along with identifying those factors associated with its development will help to assess its clinical importance within the national setting and also add to the debate on appropriate prevention strategies. METHODS: A population based birth cohort study conducted in Hampshire, UK as part of the EuroPrevall birth cohort study. 1140 infants were recruited with 823 being followed up until 2 years of age. Infants with suspected food reactions were assessed including specific IgE measurement and skin prick testing. Diagnosis of food hypersensitivity was by positive double blind, placebo-controlled food challenge (DBPCFC) where symptoms up to 48 h after the end of the food challenge were considered indicative of a food hypersensitivity. Factors associated with food hypersensitivity and its two phenotypes of IgE-mediated and non-IgE-mediated disease were modelled in a multivariable logistic regression analysis. RESULTS: Cumulative incidence of food hypersensitivity by 2 years of age was 5.0 %. The cumulative incidence for individual food allergens were hens' egg 2.7 % (1.6-3.8); cows' milk 2.4 % (1.4 3.5); peanut 0.7 % (0.1-1.3); soy 0.4 % (0.0-0.8); wheat 0.2 % (0.0-0.5) and 0.1 % (0.0-0.32) for fish. The cumulative incidence of IgE-mediated food allergy was 2.6 % with 2.1 % reacting to hens' egg. For non-IgE-mediated food allergy the cumulative incidence was 2.4 % (cows' milk 1.7 %). Predictors for any food hypersensitivity were wheeze, maternal atopy, increasing gestational age, age at first solid food introduction and mean healthy dietary pattern score. Predictors for IgE mediated allergy were eczema, rhinitis and healthy dietary pattern score whereas for non-IgE-mediated food allergy the predictors were dog in the home, healthy dietary pattern score, maternal consumption of probiotics during breastfeeding and age at first solid food introduction. CONCLUSIONS: Just under half the infants with confirmed food hypersensitivity had no demonstrable IgE. In an exploratory analysis, risk factors for this phenotype of food hypersensitivity differed from those for IgE-mediated food allergy except for a healthy infant diet which was associated with less risk for both phenotypes. PMID- 26816619 TI - Editorial. PMID- 26816618 TI - Sugars in peach fruit: a breeding perspective. AB - The last decade has been characterized by a decrease in peach (Prunus persica) fruit consumption in many countries, foremost due to unsatisfactory quality. The sugar content is one of the most important quality traits perceived by consumers, and the development of novel peach cultivars with sugar-enhanced content is a primary objective of breeding programs to revert the market inertia. Nevertheless, the progress reachable through classical phenotypic selection is limited by the narrow genetic bases of peach breeding material and by the complex quantitative nature of the trait, which is deeply affected by environmental conditions and agronomical management. The development of molecular markers applicable in MAS or MAB has become an essential strategy to boost the selection efficiency. Despite the enormous advances in 'omics' sciences, providing powerful tools for plant genotyping, the identification of the genetic bases of sugar related traits is hindered by the lack of adequate phenotyping methods that are able to address strong within-plant variability. This review provides an overview of the current knowledge of the metabolic pathways and physiological mechanisms regulating sugar accumulation in peach fruit, the main advances in phenotyping approaches and genetic background, and finally addressing new research priorities and prospective for breeders. PMID- 26816620 TI - Nanofiber-microsphere (nano-micro) matrices for bone regenerative engineering: a convergence approach toward matrix design. AB - Bone is an essential organ for health and quality of life. Due to current shortfalls in therapy for bone tissue engineering, scientists have sought the application of synthetic materials as bone graft substitutes. As a composite organic/inorganic material with significant extra cellular matrix (ECM), one way to improve bone graft substitutes may be to engineer a synthetic matrix that is influenced by the physical appearance of natural ECM networks. In this work, the authors evaluate composite, hybrid scaffolds for bone tissue engineering based on composite ceramic/polymer microsphere scaffolds with synthetic ECM-mimetic networks in their pore spaces. Using thermally induced phase separation, nanoscale fibers were deposited in the pore spaces of structurally sound microsphere-based scaffold with a density proportionate to the initial polymer concentration. Porosimetry and mechanical testing indicated no significant changes in overall pore characteristics or mechanical integrity as a result of the fiber deposition process. These scaffolds displayed adequate mechanical integrity on the scale of human trabecular bone and supported the adhesion and proliferation of cultured mouse calvarial osteoblasts. Drawing from natural cues, these scaffolds may represent a new avenue forward for advanced bone tissue engineering scaffolds. PMID- 26816621 TI - Counting CD4(+) and CD8(+) T cells in the spleen: a novel in vivo method for assessing biomaterial immunotoxicity. AB - As immunotoxicity assessments of newly developed biomaterials are often restricted to use in assessment of local tissue response at the implantation site, they do not always show an immune response acceptable to qualify them for clinical use. We tested a new method to assess systemic toxicity: counting the CD4(+) and CD8(+) cells in the spleen. Three different biomaterials were subcutaneously implanted in three groups of rats for the same time period. After 31 days, their spleens were harvested, and CD4(+) and CD8(+) cells were counted. The mean CD4(+)/CD8(+) cell counts were 24.5 +/- 3.6/19.8 +/- 4.0 (porous collagen matrix group), 25.5 +/- 7.1/21.6 +/- 3.8 [synthetic collagen matrix (Duragen(r)) group] and 28.1 +/- 4.1/19.6 +/- 3.7 (porcine dermis group). Differences in cell counts were not significant. The immunotoxic response generated against porous collagen matrix was comparable to that produced by a similar biomaterial already used clinically. This is, to the best of our knowledge, the first study on cytotoxic lymphocytes in the spleen to quantify systemic immune response to a biomaterial; however, such studies have been conducted with bacterial and viral antigens, and with vaccines. We believe that the present study provides a viable method for larger studies to confirm our current findings. PMID- 26816622 TI - Utilization of H-bond interaction of nucleobase Uralic with antitumor methotrexate to design drug carrier with ultrahigh loading efficiency and pH responsive drug release. AB - A novel Uralic (U)-rich linear-hyperbranched mono-methoxy poly (ethylene glycol) hyperbranched polyglycerol-graft-Uralic (mPEG-HPG-g-U) nanoparticle (NP) was prepared as drug carrier for antitumor methotrexate (MTX). Due to the H-bond interaction of U with MTX and hydrophobic interaction, this NP exhibited high drug loading efficiency of up to 40%, which was significantly higher than that of traditional NPs based on U-absent copolymers (<15%). In addition, MTX-loaded mPEG HPG-g-U NPs also demonstrated an acidity-accelerated drug release behavior. PMID- 26816623 TI - Gene expression profiling and mechanism study of neural stem cells response to surface chemistry. AB - To declare the mechanisms of neural stem cells (NSCs) in response to material surface chemistry, NSCs were exposed to the self-assemble monolayers of alkanethiolates on gold surfaces terminated with amine (NH2), hydroxyl (OH) and methyl (CH3) for analysis. The morphological responses of NSCs were recorded; the gene expression profilings were detected by genechips; the gene expressions data of NSCs responded to different chemical groups were declared through the gene ontology term and pathway analyses. It showed that cells behaved dissimilar on the three chemical groups, the adhesion, proliferation and migration were easier on the NH2 and OH groups; the gene expressions of NSCs were induced differently, either, involved in several functional processes and signaling pathways. CH3 group induced genes enriched much in chemistry reactions and death processes, whereas many genes of cellular nucleotide metabolism were down-regulated. NH2 group induced NSCs to express many genes of receptors on membrane, and participated in cellular signal transduction of cell adhesion and interactions, or associated with axon growth. OH group was similar to NH2 group to induce the membrane response, but it also down regulated metabolism of cells. Therefore, it declared the chemical groups affected NSCs through inner way and the NH2, OH and CH3 groups triggered the cellular gene expression in different signaling pathways. PMID- 26816624 TI - Vascular restoration therapy and bioresorbable vascular scaffold. AB - This article describes the evolution of minimally invasive intervention technologies for vascular restoration therapy from early-stage balloon angioplasty in 1970s, metallic bare metal stent and metallic drug-eluting stent technologies in 1990s and 2000s, to bioresorbable vascular scaffold (BVS) technology in large-scale development in recent years. The history, the current stage, the challenges and the future of BVS development are discussed in detail as the best available approach for vascular restoration therapy. The criteria of materials selection, design and processing principles of BVS, and the corresponding clinical trial results are also summarized in this article. PMID- 26816625 TI - Multi-responsive hydrogels for drug delivery and tissue engineering applications. AB - Multi-responsive hydrogels, or 'intelligent' hydrogels that respond to more than one environmental stimulus, have demonstrated great utility as a regenerative biomaterial in recent years. They are structured biocompatible materials that provide specific and distinct responses to varied physiological or externally applied stimuli. As evidenced by a burgeoning number of investigators, multi responsive hydrogels are endowed with tunable, controllable and even biomimetic behavior well-suited for drug delivery and tissue engineering or regenerative growth applications. This article encompasses recent developments and challenges regarding supramolecular, layer-by-layer assembled and covalently cross-linked multi-responsive hydrogel networks and their application to drug delivery and tissue engineering. PMID- 26816626 TI - Advances in the surface modification techniques of bone-related implants for last 10 years. AB - At the time of implanting bone-related implants into human body, a variety of biological responses to the material surface occur with respect to surface chemistry and physical state. The commonly used biomaterials (e.g. titanium and its alloy, Co-Cr alloy, stainless steel, polyetheretherketone, ultra-high molecular weight polyethylene and various calcium phosphates) have many drawbacks such as lack of biocompatibility and improper mechanical properties. As surface modification is very promising technology to overcome such problems, a variety of surface modification techniques have been being investigated. This review paper covers recent advances in surface modification techniques of bone-related materials including physicochemical coating, radiation grafting, plasma surface engineering, ion beam processing and surface patterning techniques. The contents are organized with different types of techniques to applicable materials, and typical examples are also described. PMID- 26816627 TI - Crosslinking strategies for preparation of extracellular matrix-derived cardiovascular scaffolds. AB - Heart valve and blood vessel replacement using artificial prostheses is an effective strategy for the treatment of cardiovascular disease at terminal stage. Natural extracellular matrix (ECM)-derived materials (decellularized allogeneic or xenogenic tissues) have received extensive attention as the cardiovascular scaffold. However, the bioprosthetic grafts usually far less durable and undergo calcification and progressive structural deterioration. Glutaraldehyde (GA) is a commonly used crosslinking agent for improving biocompatibility and durability of the natural scaffold materials. However, the nature ECM and GA-crosslinked materials may result in calcification and eventually lead to the transplant failure. Therefore, studies have been conducted to explore new crosslinking agents. In this review, we mainly focused on research progress of ECM-derived cardiovascular scaffolds and their crosslinking strategies. PMID- 26816629 TI - Important Topics in the Future of Tissue Engineering: Comments from the participants of the 5th International Conference on Tissue Engineering at Kos, Greece. PMID- 26816628 TI - Recent development of temperature-responsive surfaces and their application for cell sheet engineering. AB - Cell sheet engineering, which fabricates sheet-like tissues without biodegradable scaffolds, has been proposed as a novel approach for tissue engineering. Cells have been cultured and proliferate to confluence on a temperature-responsive cell culture surface at 37 degrees C. By decreasing temperature to 20 degrees C, an intact cell sheet can be harvested from the culture surface without enzymatic treatment. This new approach enables cells to keep their cell-cell junction, cell surface proteins and extracellular matrix. Therefore, recovered cell sheet can be easily not only transplanted to host tissue, but also constructed a three dimensional (3D) tissue by layering cell sheets. Moreover, cell sheet manipulation technology and bioreactor have been combined with the cell sheet technology to fabricate a complex and functional 3D tissue in vitro. So far, cell sheet technology has been applied in regenerative medicine for several tissues, and a number of clinical studies have been performed. In this review, recent advances in the preparation of temperature-responsive cell culture surface, the fabrication of organ-like tissue and the clinical application of cell sheet engineering are summarized and discussed. PMID- 26816630 TI - Selectivity of biopolymer membranes using HepG2 cells. AB - Bioartificial liver (BAL) system has emerged as an alternative treatment to bridge acute liver failure to either liver transplantation or liver regeneration. One of the main reasons that the efficacy of the current BAL systems was not convincing in clinical trials is attributed to the lack of friendly interface between the membrane and the hepatocytes in liver bioreactor, the core unit of BAL system. Here, we systematically compared the biological responses of hepatosarcoma HepG2 cells seeded on eight, commercially available biocompatible membranes made of acetyl cellulose-nitrocellulose mixed cellulose (CA-NC), acetyl cellulose (CA), nylon (JN), polypropylene (PP), nitrocellulose (NC), polyvinylidene fluoride (PVDF), polycarbonate (PC) and polytetrafluoroethylene (PTFE). Physicochemical analysis and mechanical tests indicated that CA, JN and PP membranes yield high adhesivity and reasonable compressive and/or tensile features with friendly surface topography for cell seeding. Cells prefer to adhere on CA, JN, PP or PTFE membranes with high proliferation rate in spheriod like shape. Actin, albumin and cytokeratin 18 expressions are favorable for cells on CA or PP membrane, whereas protein filtration is consistent among all the eight membranes. These results further the understandings of cell growth, morphology and spreading, as well as protein filtration on distinct membranes in designing a liver bioreactor. PMID- 26816632 TI - Frontiers in regenerative medical materials: Comments from the participants of the 2014 China-Korea Symposium on Biomimetic and Regenerative Medical Materials. PMID- 26816631 TI - Absorbable magnesium-based stent: physiological factors to consider for in vitro degradation assessments. AB - Absorbable metals have been widely tested in various in vitro settings using cells to evaluate their possible suitability as an implant material. However, there exists a gap between in vivo and in vitro test results for absorbable materials. A lot of traditional in vitro assessments for permanent materials are no longer applicable to absorbable metallic implants. A key step is to identify and test the relevant microenvironment and parameters in test systems, which should be adapted according to the specific application. New test methods are necessary to reduce the difference between in vivo and in vitro test results and provide more accurate information to better understand absorbable metallic implants. In this investigative review, we strive to summarize the latest test methods for characterizing absorbable magnesium-based stent for bioabsorption/biodegradation behavior in the mimicking vascular environments. Also, this article comprehensively discusses the direction of test standardization for absorbable stents to paint a more accurate picture of the in vivo condition around implants to determine the most important parameters and their dynamic interactions. PMID- 26816633 TI - Effect of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide concentrations on the mechanical and biological characteristics of cross-linked collagen fibres for tendon repair. AB - Reconstituted type I collagen fibres have received considerable interest as tendon implant materials due to their chemical and structural similarity to the native tissue. Fibres produced through a semi-continuous extrusion process were cross-linked with different concentrations of the zero-length cross-linker 1 ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) in combination with N hydroxysuccinimide (NHS). Tensile properties of the fibres were considered, along with imaging of both surface structure and fibrillar alignment. Resistance of the fibres to bacterial collagenase was investigated and fibre sections seeded with human tendon cells for biological characterization, including cell adhesion and proliferation. The work clearly demonstrated that whilst the concentration of EDC and NHS had no significant effect on the mechanics, a higher concentration was associated with higher collagenase resistance, but also provided a less attractive surface for cell adhesion and proliferation. A lower cross-linking concentration offered a more biocompatible material without reduction in mechanics and with a potentially more optimal degradability. PMID- 26816634 TI - Silk fibroin/poly (vinyl alcohol) blend scaffolds for controlled delivery of curcumin. AB - A silk fibroin/poly (vinyl alcohol) porous scaffold with a water vapor transmission rate of 2125 +/- 464 g/m(2)/day has been developed via thermally induced phase separation (gelation) and freeze-drying process. A hierarchical architecture of micropores and nanofibers was observed inside the scaffolds, and the related structures were analyzed. The viability and proliferation of 3T3 fibroblasts were examined, which indicated that the scaffolds exerted low cytotoxicity. After loading curcumin, the scaffolds can suppress the growth of 3T3 fibroblasts. The release behavior of curcumin from the scaffolds was investigated. At pH = 7.2, the release profiles showed no significant difference for the loading amounts of 0.5 mg and 0.25 mg per sample. Meanwhile, the cumulative amount of released drug at pH = 5.7 was significantly more than that in neutral solution due to more degradation of the scaffolds. It was suggested that the silk fibroin/poly (vinyl alcohol) blend scaffolds could be potentially used as wound dressing materials. PMID- 26816635 TI - Degradation and biological properties of Ca-P contained micro-arc oxidation self sealing coating on pure magnesium for bone fixation. AB - Poor corrosion resistance is one of the main disadvantages for biodegradable magnesium-based metals, especially applied for bone fixation, where there is a high demand of bio-mechanical strength and stability. Surface coating has been proved as an effective method to control the in vivo degradation. In this study a Ca-P self-sealing micro-arc oxidation (MAO) coating was studied to verify its efficacy and biological properties by in vitro and in vivo tests. It was found that the MAO coating could effectively retard the degradation according to immersion and electrochemical tests as well as 3D reconstruction by X-ray tomography after implantation. The MAO coating exhibited no toxicity and could stimulate the new bone formation. Therefore, the Ca-P self-sealing MAO coating could be a potential candidate for application of biodegradable Mg-based implant in bone fixations. PMID- 26816636 TI - Promotion of peripheral nerve regeneration and prevention of neuroma formation by PRGD/PDLLA/beta-TCP conduit: report of two cases. AB - In the field of nerve repair, one major challenge is the formation of neuroma. However, reports on both the promotion of nerve regeneration and prevention of traumatic neuroma in the clinical settings are rare in the field of nerve repair. One of the reasons could be the insufficiency in the follow-up system. We have conducted 33 cases of nerve repair using PRGD/PDLLA/beta-TCP conduit without any sign of adverse reaction, especially no neuroma formation. Among them, we have selected two cases as representatives to report in this article. The first case was a patient with an upper limb nerve wound was bridged by PRGD/PDLLA/beta-TCP conduit and a plate fixation was given. After nearly 3-years' follow-up, the examination results demonstrated that nerve regeneration effect was very good. When the reoperation was performed to remove the steel plate we observed a uniform structure of the regenerated nerve without the formation of neuroma, and to our delight, the implanted conduit was completely degraded 23 months after the implantation. The second case had an obsolete nerve injury with neuroma formation. After removal of the neuroma, the nerve was bridged by PRGD/PDLLA/beta TCP conduit. Follow-up examinations showed that the structure and functional recovery were improved gradually in the 10-month follow-up; no end-enlargement and any other abnormal reaction associated with the characteristic of neuroma were found. Based on our 33-case studies, we have concluded that PRGD/PDLLA/beta TCP nerve conduit could both promote nerve regeneration and prevent neuroma formation; therefore, it is a good alternative for peripheral nerve repair. PMID- 26816638 TI - Important topics in the future of biomaterials and stem cells for bone tissue engineering: Comments from the participants of the International Symposium on Recent Trend of Biomaterials and Stem Cells for Bone Tissue Engineering at Changchun, China. PMID- 26816637 TI - Surface modification of biodegradable magnesium and its alloys for biomedical applications. AB - Magnesium and its alloys are being paid much attention recently as temporary implants, such as orthopedic implants and cardiovascular stents. However, the rapid degradation of them in physiological environment is a major obstacle preventing their wide applications to date, which will result in rapid mechanical integrity loss or even collapse of magnesium-based implants before injured tissues heal. Moreover, rapid degradation of the magnesium-based implants will also cause some adverse effects to their surrounding environment, such as local gas cavity around the implant, local alkalization and magnesium ion enrichment, which will reduce the integration between implant and tissue. So, in order to obtain better performance of magnesium-based implants in clinical trials, special alloy designs and surface modifications are prerequisite. Actually, when a magnesium-based implant is inserted in vivo, corrosion firstly happens at the implant-tissue interface and the biological response to implant is also determined by the interaction at this interface. So the surface properties, such as corrosion resistance, hemocompatibility and cytocompatibility of the implant, are critical for their in vivo performance. Compared with alloy designs, surface modification is less costly, flexible to construct multi-functional surface and can prevent addition of toxic alloying elements. In this review, we would like to summarize the current investigations of surface modifications of magnesium and its alloys for biomedical application. The advantages/disadvantages of different surface modification methods are also discussed as a suggestion for their utilization. PMID- 26816639 TI - Self-defensive nano-assemblies from camptothecin-based antitumor drugs. AB - Camptothecin (CPT)-based drugs always undergo the reversible, pH-dependent lactone ring-opening reaction, yielding the inactive but toxic carboxylate form. Self-assembly strategy provides an effective route for preserving their bio stability. In this article, nano-sized self-assemblies from CPT-based antitumor drugs were simply built up by directly diluting the stock dimethylsulfoxide solutions of (S)-(+)-CPT, (S)-10-hydroxyl camptothecin and carboxylic CPT with water/phosphate-buffered saline solution. Because of their different molecular structures in A-ring or modification on the 20-OH group, CPT self-assembled into helical nano-ribbons, whereas 10-hydroxycamptothecin and carboxylic CPT self aggregated into flat nano-ribbons and cylindric nano-rods, respectively. Attractively, the self-assembly of CPT-based drugs could occur within 1 min at a low concentration of 1 * 10(-5 )M. Adopting the J-type self-aggregation, self assemblies were stable in aqueous solution and could effectively protect the CPT based drugs from hydrolysis, which thereby kept their bioactivity for tumor therapy. PMID- 26816640 TI - Biomolecular functionalization for enhanced cell-material interactions of poly(methyl methacrylate) surfaces. AB - The integration of implants or medical devices into the body tissues requires of good cell-material interactions. However, most polymeric materials used for these applications lack on biological cues, which enhanced mid- and long-term implant failure due to weak integration with the surrounding tissue. Commonly used strategies for tissue-material integration focus on functionalization of the material surface by means of natural proteins or short peptides. However, the use of these biomolecules involves major drawbacks such as immunogenic problems and oversimplification of the constructs. Here, designed elastin-like recombinamers (ELRs) are used to enhance poly(methyl methacrylate) surface properties and compared against the use of short peptides. In this study, cell response has been analysed for different functionalization conditions in the presence and absence of a competing protein, which interferes on surface-cell interaction by unspecific adsorption on the interface. The study has shown that ELRs can induce higher rates of cell attachment and stronger cell anchorages than short peptides, being a better choice for surface functionalization. PMID- 26816641 TI - The effects of icariine concentration on osteoclasts bone resorption induced by titanium particles in vitro. AB - In artificial joint replacement, osteoclast bone resorption induced by wear debris of the implant is a main reason for aseptic loosening. To extend the life of the prosthesis, detailed mechanisms of aseptic loosening and the ways to prevent it should be explored. The aim of this study was to investigate the in vitro effect of icariine on the bone resorption of osteoclasts induced by titanium particles. Macrophage colony stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL) were used to generate osteoclasts from RAW264.7 precursors. The proliferation of RAW264.7 precursors in the presence of different doses of icariine was evaluated by MTT assay. The cells were treated with titanium particles, titanium particles with icariine and culture medium only (control), respectively. At 48 h after treatment, the expression level of receptor activator of NF-kB (RANK) was detected by ELISA, and messenger RNA (mRNA) levels of tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinase 9 (MMP-9), carbonic anhydrase II (CAII) and Cathepsin K (CtsK) were determined by real-time polymerase chain reaction. Western blot was applied to analyze the expression levels of TRAP, RANK and CtsK. In addition, bone chips were cultured in the above conditions, and Toluidine blue staining was then employed to calculate the number and area of resorption pits in the bone chips. After treatment with icariine, expression level of RANK was significantly decreased in the RAW264.7 cell that induced by titanium particle and its cultural medium, mRNA and protein levels of TRAP, CAII, MMP-9 and CtsK were reduced as well. In addition, the numbers of bone resorption pits and areas on bone slices were both reduced by icariine challenging. Icariine could inhibit bone resorption of osteoclast induced by titanium particle, and it might be used as a promising drug for treating of aseptic loosening. PMID- 26816643 TI - Neuropeptide Y receptors: a promising target for cancer imaging and therapy. AB - Neuropeptide Y (NPY) was first identified from porcine brain in 1982, and plays its biological functions in humans through NPY receptors (Y1, Y2, Y4 and Y5). NPY receptors are known to mediate various physiological functions and involve in a majority of human diseases, such as obesity, hypertension, epilepsy and metabolic disorders. Recently, NPY receptors have been found to be overexpressed in many cancers, so they emerged as promising target in cancer diagnosis and therapy. This review focuses on the latest research about NPY and NPY receptors, and summarizes the current knowledge on NPY receptors expression in cancers, selective ligands for NPY receptors and their application in cancer imaging and therapy. PMID- 26816644 TI - Biomimetic biphasic scaffolds for osteochondral defect repair. AB - The osteochondral defects caused by vigorous trauma or physical disease are difficult to be managed. Tissue engineering provides a possible option to regenerate the damaged osteochondral tissues. For osteochondral reconstruction, one intact scaffold should be considered to support the regeneration of both cartilage and subchondral bone. Therefore, the biphasic scaffolds with the mimic structures of osteochondral tissues have been developed to close this chasm. A variety of biomimetic bilayer scaffolds fabricated from natural or synthetic polymers, or the ones loading with growth factors, cells, or both of them make great progresses in osteochondral defect repair. In this review, the preparation and in vitro and/or in vivo verification of bioinspired biphasic scaffolds are summarized and discussed, as well as the prospect is predicted. PMID- 26816645 TI - Ultrasound-triggered dual-drug release from poly(lactic-co-glycolic acid)/mesoporous silica nanoparticles electrospun composite fibers. AB - The aim of this study was to achieve on-demand controlled drug release from the dual-drug-loaded poly(lactic-co-glycolic acid)/mesoporous silica nanoparticles electrospun composite fibers by the application of ultrasound irradiation. Two drugs were loaded in different part of the composite fibrous materials, and it was found that ultrasound as an external stimulus was able to control release of drugs due to both its thermal effect and non-thermal effect. With the selective irradiation of ultrasound, the drug carrier enabled to realize controlled release, and because of different location in fibers and sensitivity of two different kinds of drugs to ultrasound irradiation, the release rate of two drugs was different. These results indicated that ultrasound irradiation was a facile method to realize the on-demand controlled release of two drugs from the electrospun fibers. PMID- 26816642 TI - Bridging the lesion-engineering a permissive substrate for nerve regeneration. AB - Biomaterial-based strategies to restore connectivity after lesion at the spinal cord are focused on bridging the lesion and providing an favourable substrate and a path for axonal re-growth. Following spinal cord injury (SCI) a hostile environment for neuronal cell growth is established by the activation of multiple inhibitory mechanisms that hamper regeneration to occur. Implantable scaffolds can provide mechanical support and physical guidance for axon re-growth and, at the same time, contribute to alleviate the hostile environment by the in situ delivery of therapeutic molecules and/or relevant cells. Basic research on SCI has been contributing with the description of inhibitory mechanisms for regeneration as well as identifying drugs/molecules that can target inhibition. This knowledge is the background for the development of combined strategies with biomaterials. Additionally, scaffold design is significantly evolving. From the early simple hollow conduits, scaffolds with complex architectures that can modulate cell fate are currently being tested. A number of promising pre-clinical studies combining scaffolds, cells, drugs and/or nucleic acids are reported in the open literature. Overall, it is considered that to address the multi factorial inhibitory environment of a SCI, a multifaceted therapeutic approach is imperative. The progress in the identification of molecules that target inhibition after SCI and its combination with scaffolds and/or cells are described and discussed in this review. PMID- 26816646 TI - Comparative study of flexural strength test methods on CAD/CAM Y-TZP dental ceramics. AB - Clinically, fractures are the main cause of computer-aided design and computer aided manufacturing (CAD/CAM) 3 mol%-yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) all-ceramic dental restorations failure because of repetitive occlusal loading. The goal of this work is to study the effect of test methods and specimen's size on the flexural strength of five ceramic products. Both bi axial flexure test (BI) and uni-axial flexure tests (UNI), including three-point flexure test (3PF) and four-point flexure test (4PF), are used in this study. For all five products, the flexural strength is as follows: BI > 3PF > 4PF. Furthermore, specimens with smaller size (3PF-s) have higher values than the bigger ones (3PF). The difference between BI and UNI resulted from the edge flaws in ceramic specimens. The relationship between different UNI (including 3PF-s, 3PF and 4PF) can be explained according to Weibull statistical fracture theory. BI is recommended to evaluate the flexural strength of CAD/CAM Y-TZP dental ceramics. PMID- 26816647 TI - Clinical evaluation following the use of mineralized collagen graft for bone defects in revision total hip arthroplasty. AB - Revision total hip arthroplasty (THA) with massive bone loss has been a real challenge for orthopaedic surgeons. Here we describe an approach using mineralized collagen (MC) graft to reconstruct acetabulum and femur with massive bone defects. We identified 89 patients suffering acetabular or femoral bone defects after primary THA, who required revision THA for this study. During the surgery, MC was applied to reconstruct both the acetabular and femoral defects. Harris hip score was used to evaluate hip function while radiographs were taken to estimate bone formation in the defect regions. The average follow-up period was 33.6 +/- 2.4 months. None of the components needed re-revised. Mean Harris hip scores were 42.5 +/- 3.5 before operation, 75.2 +/- 4.0 at 10th month and 95.0 +/- 3.6 at the final follow-up. There were no instances of deep infection, severe venous thrombosis or nerve palsy. The present study demonstrated that MC graft can serve as a promising option for revision THA with massive bone deficiency. Meanwhile, extended follow-up is needed to further prove its long term performance. PMID- 26816648 TI - A new method to standardize CBCT for quantitative evaluation of alveolar ridge preservation in the mandible: a case report and review of the literature. AB - Cone-beam computerized tomography (CBCT) is an effective technique for assessment of changes to the alveolar ridge (AR). However, its accuracy and reliability could be improved by standardization of imaging positions to remain unchanged during measurements. In this study, an alveolar ridge preservation procedure was performed on a left third molar (38) socket by filling it with a radiotransparent synthetic bone graft, mineralized collagen (MC). Photographic, X-ray and CBCT images were captured before and 3, 6 and 12 months after surgery. A new method was developed to standardize CBCT for quantitative evaluation. Obtained CBCT images showed good comparability. The post-extraction alveolar width and height were both over 95% of the original values, but some resorption of the lingual bone wall (>50%) and inter-crestal bone (>30%). It is concluded that an effective positional standardization method was developed for CBCT assessment of AR dimensional changes in the posterior mandible. The use of MC in combination with a collagen membrane improved dimensional preservation of the AR. PMID- 26816649 TI - Tissue toxicity following the vaginal administration of nanosilver particles in rabbits. AB - Nanosilver particles are used in various clinical settings because of their antibacterial properties. However, their safety evaluation when used for gynaecological disorders has not been established. Nanosilver particles were administrated in the vagina of New Zealand rabbits, and the pathological appearance of the surrounding tissue was examined by hematoxylin-eosin staining and transmission electron microscopy (TEM) after 1 and 3 days of treatment. The nanosilver content was assessed by plasma mass spectrometry, and the presence of particles in the hepatic portal vein blood was assessed by TEM. The results of our study show that the vaginal administration of nanosilver particles caused ultrastructural changes to the vaginal mucosa, urethra and rectum, with accumulation of particles in all tissues. These results demonstrate a new migration route of nanosilver particles following vaginal administration. They also demonstrate, for the first time, that the vaginal administration of nanosilver particles can enter the blood circulation system by examining the hepatic portal vein blood under the TEM which is the most direct visualized evidence. PMID- 26816650 TI - Modelling the regenerative niche: a major challenge in biomaterials research. AB - By definition, biomaterials are developed for clinical application. In the field of regenerative medicine their principal function is to play a significant, and, if possible, an instructive role in tissue healing. In the last analysis the latter involves targeting the 'regenerative niche'. The present paper will address the problem of simulating this niche in the laboratory and adopts a life science approach involving the harnessing of heterotypic cellular communication to achieve this, that is, the ability of cells of different types to mutually influence cellular functions. Thus, co-culture systems using human cells are the methodological focus and will concern four exemplary fields of regeneration, namely, bone, soft tissue, lower respiratory tract and airway regeneration. The working hypothesis underlying this approach is that in vitro models of higher complexity will be more clinically relevant than simple monolayer cultures of transformed cell lines in testing innovative strategies with biomaterials for regeneration. PMID- 26816651 TI - Biocompatibility and degradation of tendon-derived scaffolds. AB - Decellularized extracellular matrix has often been used as a biomaterial for tissue engineering applications. Its function, once implanted can be crucial to determining whether a tissue engineered construct will be successful, both in terms of how the material breaks down, and how the body reacts to the material's presence in the first place. Collagen is one of the primary components of extracellular matrix and has been used for a number of biomedical applications. Scaffolds comprised of highly aligned collagen fibrils can be fabricated directly from decellularized tendon using a slicing, stacking, and rolling technique, to create two- and three-dimensional constructs. Here, the degradation characteristics of the material are evaluated in vitro, showing that chemical crosslinking can reduce degradation while maintaining fiber structure. In vivo, non-crosslinked and crosslinked samples are implanted, and their biological response and degradation evaluated through histological sectioning, trichrome staining, and immunohistochemical staining for macrophages. Non-crosslinked samples are rapidly degraded and lose fiber morphology while crosslinked samples retain both macroscopic structure as well as fiber orientation. The cellular response of both materials is also investigated. The in vivo response demonstrates that the decellularized tendon material is biocompatible, biodegradable and can be crosslinked to maintain surface features for extended periods of time in vivo. This study provides material characteristics for the use of decellularized tendon as biomaterial for tissue engineering. PMID- 26816652 TI - Properties of carbon nanotube-dispersed Sr-hydroxyapatite injectable material for bone defects. AB - This study concerns the synthesis of gel materials based on carbon nanotubes dispersed strontium-modified hydroxyapatite (Sr-HA) at different compositions obtained by sol-gel technology and their influence on human-bone-marrow-derived mesenchymal stem cells. Furthermore, an evaluation of the influence of nanotubes and Strontium on physico-chemical, morphological, rheological and biological properties of hydroxyapatite gel was also performed. Morphological analysis (scanning electron microscopy) shows a homogeneous distribution of modified nanotubes in the ceramic matrix improving the bioactive properties of materials. The biological investigations proved that Sr-HA/carbon nanotube gel containing 0 20 mol (%) of Sr showed no toxic effect and promote the expression of early and late markers of osteogenic differentiation in cell culture performed in basal medium without osteogenic factors. Finally, the SrHA/carbon nanotube gels could have a good potential application as filler in bone repair and regeneration and may be used in the osteoporotic disease treatment. PMID- 26816653 TI - Analysis of intellectual properties on animal-derived regenerative, implantable medical devices. AB - This article analyses and summarizes issues of intellectual property involved in animal-derived regenerative, implantable medical devices (ADRIMD) in order to better understand global trends in patent applications and disclosures, the legal status of patent families (i.e. sets of patents filed in various countries to protect a single invention), and International Patent Classification topics such as main assignee and core expertise. Analysis of research trends will enhance and inform the decision-making capacity of researchers, investors, government regulators and other stake-holders as they undertake to develop, deploy, invest in or regulate ADRIMD. PMID- 26816654 TI - Comparison of bone regeneration in alveolar bone of dogs on mineralized collagen grafts with two composition ratios of nano-hydroxyapatite and collagen. AB - To study the effect of two composition ratios of nano-hydroxyapatite and collagen (NHAC) composites on repairing alveolar bone defect of dogs. Eighteen healthy adult dogs were randomly divided into three groups. Two kinds of the NHAC composites were prepared according to the constituent ratios of 3:7 and 5:5; immediately after extraction of the mandibular second premolars, each kind of the NHAC composite was implanted into extraction socket, respectively: Group I, nHA/Col = 3:7; Group II, nHA/Col = 5:5 and Group III, blank control group. The bone-repairing ability of the two grafts was separately analyzed by morphometric measurement, X-ray tomography examination and biomechanical analysis at 1st, 3rd and 6th month post-surgical, respectively. The NHAC composites were absorbed gradually after implanting into alveolar bone defect and were replaced by new bone. The ratios of new bone formation of Group I was significantly higher than that of Group II after 3 months (P < 0.05). The structure and bioactive performance can be improved when the ratio between the collagen and the hydroxyapatite was reasonable, and the repairing ability and effect in extraction sockets are obviously better. PMID- 26816655 TI - In vitro corrosion of pure magnesium and AZ91 alloy-the influence of thin electrolyte layer thickness. AB - In vivo degradation predication faces a huge challenge via in vitro corrosion test due to the difficulty for mimicking the complicated microenvironment with various influencing factors. A thin electrolyte layer (TEL) cell for in vitro corrosion of pure magnesium and AZ91 alloy was presented to stimulate the in vivo corrosion in the micro-environment built by the interface of the implant and its neighboring tissue. The results demonstrated that the in vivo corrosion of pure Mg and the AZ91 alloy was suppressed under TEL condition. The AZ91 alloy was more sensitive than pure Mg to the inhibition of corrosion under a TEL thickness of less than 200 um. The TEL thickness limited the distribution of current, and thus localized corrosion was more preferred to occur under TEL condition than in bulk solution. The TEL cell might be an appropriate approach to simulating the in vivo degradation of magnesium and its alloys. PMID- 26816656 TI - Polyethyleneimine-modified calcium carbonate nanoparticles for p53 gene delivery. AB - In this study, calcium carbonate (CaCO3) nanoparticles with spherical structure were regulated by arginine and successfully synthesized via a facile co precipitation method. The average particle size of as-prepared CaCO3 was about 900 nm. The properties of nanostructured CaCO3 particles were characterized by scanning electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction and size distribution. After modified with polyethyleneimine (PEI), the ability of PEI-CaCO3 nanoparticles to carry GFP-marked p53 gene (pEGFP-C1 p53) into cancer cells to express P53 protein were studied. Meanwhile, the cytotoxicity, transfection efficiency, cells growth inhibition and the ability to induce apoptosis by expressed P53 protein were conducted to evaluate the performances of PEI-CaCO3 nanoparticles. The results show that prepared PEI-CaCO3 nanoparticles had good biocompatibility and low cytotoxicity in a certain concentration range. PEI-CaCO3 effectively transfected pEGFP-C1 gene into epithelial-like cancer cells. And with the expression of GFP-P53 fusion protein, pEGFP-C1-p53-gene-loaded PEI-CaCO3 particles significantly reduced the proliferation of cancer cells. These findings indicate that our PEI-modified CaCO3 nanoparticles are potential to be successfully used as carriers for gene therapy. PMID- 26816657 TI - Nomogram Estimating the Probability of Intraabdominal Abscesses after Gastrectomy in Patients with Gastric Cancer. AB - PURPOSE: Intraabdominal abscess is one of the most common reasons for re hospitalization after gastrectomy. This study aimed to develop a model for estimating the probability of intraabdominal abscesses that can be used during the postoperative period. MATERIALS AND METHODS: We retrospectively reviewed the clinicopathological data of 1,564 patients who underwent gastrectomy for gastric cancer between 2010 and 2012. Twenty-six related markers were analyzed, and multivariate logistic regression analysis was used to develop the probability estimation model for intraabdominal abscess. Internal validation using a bootstrap approach was employed to correct for bias, and the model was then validated using an independent dataset comprising of patients who underwent gastrectomy between January 2008 and March 2010. Discrimination and calibration abilities were checked in both datasets. RESULTS: The incidence of intraabdominal abscess in the development set was 7.80% (122/1,564). The surgical approach, operating time, pathologic N classification, body temperature, white blood cell count, C-reactive protein level, glucose level, and change in the hemoglobin level were significant predictors of intraabdominal abscess in the multivariate analysis. The probability estimation model that was developed on the basis of these results showed good discrimination and calibration abilities (concordance index=0.828, Hosmer-Lemeshow chi-statistic P=0.274). Finally, we combined both datasets to produce a nomogram that estimates the probability of intraabdominal abscess. CONCLUSIONS: This nomogram can be useful for identifying patients at a high risk of intraabdominal abscess. Patients at a high risk may benefit from further evaluation or treatment before discharge. PMID- 26816658 TI - Analysis of new bone, cartilage, and fibrosis tissue in healing murine allografts using whole slide imaging and a new automated histomorphometric algorithm. AB - Histomorphometric analysis of histologic sections of normal and diseased bone samples, such as healing allografts and fractures, is widely used in bone research. However, the utility of traditional semi-automated methods is limited because they are labor-intensive and can have high interobserver variability depending upon the parameters being assessed, and primary data cannot be re analyzed automatically. Automated histomorphometry has long been recognized as a solution for these issues, and recently has become more feasible with the development of digital whole slide imaging and computerized image analysis systems that can interact with digital slides. Here, we describe the development and validation of an automated application (algorithm) using Visiopharm's image analysis system to quantify newly formed bone, cartilage, and fibrous tissue in healing murine femoral allografts in high-quality digital images of H&E/alcian blue-stained decalcified histologic sections. To validate this algorithm, we compared the results obtained independently using OsteoMeasure(TM) and Visiopharm image analysis systems. The intraclass correlation coefficient between Visiopharm and OsteoMeasure was very close to one for all tissue elements tested, indicating nearly perfect reproducibility across methods. This new algorithm represents an accurate and labor-efficient method to quantify bone, cartilage, and fibrous tissue in healing mouse allografts. PMID- 26816659 TI - Age-dependent Muscle Adaptation after Chronic Stretch-shortening Contractions in Rats. AB - Age-related differences in contraction-induced adaptation have been well characterized especially for young and old rodent models but much less so at intermediate ages. Therefore, additional research is warranted to determine to what extent alterations in adaptation are due to maturation versus aging per se. The purpose of our study was to evaluate muscles of Fisher 344XBrown Norway rats of various ages following one month of exposure to stretch-shortening contractions (SSCs). With exposure, muscles mass increased by ~10% for 27 and 30 month old rats vs. ~20% for 3 and 6 month old rats (P < 0.05). For 3 month old rats, maximum isometric force and dynamic peak force increased by 22 +/- 8% and 27 +/- 10%, respectively (P < 0.05). For 6 month old rats, these forces were unaltered by exposure and positive work capacity diminished by 27 +/- 2% (P = 0.006). By 30 months of age, age-related deficits in maximum isometric force, peak force, negative work, and positive work were apparent and SSC exposure was ineffective at counteracting such deficits. Recovery from fatigue was also tested and exposure-induced improvements in fatigue recovery were indicated for 6 month old rats and to a lesser extent for 3 month old rats whereas no such effect was observed for older rats. Alterations in fatigue recovery were accompanied by evidence of substantial type IIb to IIx fiber type shifting. These results highlight the exceptional adaptive capacity for strength at a young age, the inclination for adaptation in fatigue recovery at early adulthood, and diminished adaptation for muscle performance in general beginning at late adulthood. Such findings motivate careful investigation to determine appropriate SSC exposures at all stages of life. PMID- 26816660 TI - Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity. AB - Stroke is the second leading cause of death worldwide. The prognostic influence of body temperature on acute stroke in patients has been recently reported; however, hypothermia has confounded experimental results in animal stroke models. This work aimed to investigate how body temperature could prognose stroke severity as well as reveal a possible mitochondrial mechanism in the association of body temperature and stroke severity. Lipopolysaccharide (LPS) compromises mitochondrial oxidative phosphorylation in cerebrovascular endothelial cells (CVECs) and worsens murine experimental stroke. In this study, we report that LPS (0.1 mg/kg) exacerbates stroke infarction and neurological deficits, in the mean time LPS causes temporary hypothermia in the hyperacute stage during 6 hours post stroke. Lower body temperature is associated with worse infarction and higher neurological deficit score in the LPS-stroke study. However, warming of the LPS stroke mice compromises animal survival. Furthermore, a high dose of LPS (2 mg/kg) worsens neurological deficits, but causes persistent severe hypothermia that conceals the LPS exacerbation of stroke infarction. Mitochondrial respiratory chain complex I inhibitor, rotenone, replicates the data profile of the LPS-stroke study. Moreover, we have confirmed that rotenone compromises mitochondrial oxidative phosphorylation in CVECs. Lastly, the pooled data analyses of a large sample size (n=353) demonstrate that stroke mice have lower body temperature compared to sham mice within 6 hours post-surgery; the body temperature is significantly correlated with stroke outcomes; linear regression shows that lower body temperature is significantly associated with higher neurological scores and larger infarct volume. We conclude that post-stroke body temperature predicts stroke severity and mitochondrial impairment in CVECs plays a pivotal role in this hypothermic response. These novel findings suggest that body temperature is prognostic for stroke severity in experimental stroke animal models and may have translational significance for clinical stroke patients - targeting endothelial mitochondria may be a clinically useful approach for stroke therapy. PMID- 26816661 TI - Evaluation of Cardiac Autonomic Functions in Older Parkinson's Disease Patients: a Cross-Sectional Study. AB - In Parkinson's disease (PD), non-motor symptoms may occur such as autonomic dysfunction. We aimed to evaluate both parasympathetic and sympathetic cardiovascular autonomic dysfunction in older PD cases. 84 PD cases and 58 controls, for a total of 142, participated in the study. Parasympathetic tests were performed using electrocardiography. Sympathetic tests were assessed by blood pressure measurement and 24-hour ambulatory blood pressure measurement. The prevalence of orthostatic hypotension in PD patients was 40.5% in PD patients and 24.1% in the control group (p> 0.05). The prevalence of postprandial hypotension was 47.9% in the PD group and 27.5% in the controls (p <0.05). The prevalence of impairment in heart rate response to deep breathing was 26.2% in the PD group and 6.9% in the control group (p <0.05). The prevalence of postprandial hypotension in PD with orthostatic hypotension was 94% and 16% in PD patients without orthostatic hypotension (p <0.05). The prevalence of impairment in heart rate response to deep breathing was 52.9% in PD patients with orthostatic hypotension and 8% in PD cases without orthostatic hypotension (p<0.05). The prevalence of impairment in heart rate response to postural change was 41% in PD cases with orthostatic hypotension and 12% in PD cases without orthostatic hypotension (p <0.05).Although there are tests for assessing cardiovascular autonomic function that are more reliable, they are more complicated, and evaluation of orthostatic hypotension by blood pressure measurement and cardiac autonomic tests by electrocardiography are recommended since these tests are cheap and easy. PMID- 26816662 TI - Association between Apolipoprotein C-III Gene Polymorphisms and Coronary Heart Disease: A Meta-analysis. AB - Polymorphisms in the apolipoprotein C-III (APOC3) gene have been reported to be associated with coronary heart disease (CHD), but the data so far have been conflicting. To derive a more precise estimation of these associations, we performed a meta-analysis to investigate the three main polymorphisms (SstI, T 455C, C-482T) of APOC3 in all published studies. Databases including PubMed, Web of Science, Wanfang, SinoMed and CNKI were systematically searched. The association was assessed using odds ratios (ORs) with 95% confidence intervals (CIs). The statistical analysis was performed using Review Manager 5.3.3 and Stata 12.0. A total of 31 studies have been identified. The pooled odds ratio (OR) for the association between the APOC3 gene polymorphisms and CHD and its corresponding 95% confidence interval (95% CI) were evaluated by random or fixed effect models. A statistical association between APOC3 SstI polymorphism and CHD susceptibility was observed under an allelic contrast model (P= 0.003, OR = 1.14, 95% CI = 1.05-1.24), dominant genetic model (P= 0.01, OR = 1.14, 95% CI = 1.03 1.26), and recessive genetic model (P= 0.02, OR = 1.35, 95% CI = 1.06-1.71), respectively. A significant association between the APOC3 T-455C polymorphism and CHD was also detected under an allelic contrast (P < 0.0001, OR = 1.19, 95% CI = 1.10-1.29), dominant genetic model (P= 0.0003, OR = 1.24, 95% CI = 1.11-1.39) and recessive genetic model (P= 0.04, OR = 1.30, 95% CI = 1.01-1.67). No significant association between the APOC3 C-482T polymorphism and CHD was found under an allelic model (P= 0.94, OR = 1.00, 95% CI = 0.93-1.08), dominant genetic model (P= 0.20, OR = 1.07, 95% CI = 0.97-1.18) or recessive genetic model (P= 0.13, OR = 0.90, 95% CI = 0.79-1.03). This meta-analysis revealed that the APOC3 SstI and T-455C polymorphisms significantly increase CHD susceptibility. No significant association was observed between the APOC3 C-482T polymorphism and CHD susceptibility. PMID- 26816663 TI - Quality of Life Impact Related to Foot Health in a Sample of Older People with Hallux Valgus. AB - Hallux Valgus (HV) is a highly prevalent forefoot deformity in older people associated with progressive subluxation and osteoarthritis of the first metatarsophalangeal (MTP) joint and it is believed to be associated with varying degrees of HV effect on the quality of life related to foot health. The aim of this study is to compare the impact of varying degrees of HV on foot health in a sample of older people. The sample consisted of 115 participants, mean age 76.7 +/- 9.1, who attended an outpatient center where self-report data were recorded. The degree of HV deformity was determined in both feet using the Manchester Scale (MS) from stage 1 (mild) to 4 (very severe). Scores obtained on the Foot Health Status Questionnaire (FHSQ) were compared. This has 13 questions that assess 4 health domains of the feet, namely pain, function, general health and footwear. The stage 4 of HV shown lower scores for the footwear domain (11.23 +/- 15.6); general foot health (27.62 +/- 19.1); foot pain (44.65 +/- 24.5); foot function (53.04 +/- 27.2); vigour (42.19 +/- 16.8); social capacity (44.46 +/- 28.1); and general health (41.15 +/- 25.5) compared with stage 1 of HV (P<0.05) and there were no differences of physical activity (62.81 +/- 24.6). Often, quality of life decreases in the elderly population based in large part on their foot health. There is a progressive reduction in health in general and foot health with increasing severity of hallux valgus deformity which appears to be associated with the presence of greater degree of HV, regardless of gender. PMID- 26816664 TI - mHealth For Aging China: Opportunities and Challenges. AB - The aging population with chronic and age-related diseases has become a global issue and exerted heavy burdens on the healthcare system and society. Neurological diseases are the leading chronic diseases in the geriatric population, and stroke is the leading cause of death in China. However, the uneven distribution of caregivers and critical healthcare workforce shortages are major obstacles to improving disease outcome. With the advancement of wearable health devices, cloud computing, mobile technologies and Internet of Things, mobile health (mHealth) is rapidly developing and shows a promising future in the management of chronic diseases. Its advantages include its ability to improve the quality of care, reduce the costs of care, and improve treatment outcomes by transferring in-hospital treatment to patient-centered medical treatment at home. mHealth could also enhance the international cooperation of medical providers in different time zones and the sharing of high-quality medical service resources between developed and developing countries. In this review, we focus on trends in mHealth and its clinical applications for the prevention and treatment of diseases, especially aging-related neurological diseases, and on the opportunities and challenges of mHealth in China. Operating models of mHealth in disease management are proposed; these models may benefit those who work within the mHealth system in developing countries and developed countries. PMID- 26816665 TI - Effects of Use and Disuse on Non-paralyzed and Paralyzed Skeletal Muscles. AB - Skeletal muscle is an integral part of the somatic nervous system and plays a primary role in the performance of physical activities. Because physical activity is vital to countering the effects of aging and age related diseases and is a key component in the maintenance of healthy body composition it is important to understand the effects of use and disuse on skeletal muscle. While voluntary muscle activity provides optimal benefits to muscle and the maintenance of healthy body composition, neuromuscular electrical stimulation may be a viable alternative activity for individuals with paralysis. Body composition with a healthy muscle to fat ratio has been associated with healthy blood lipid and glucose profiles that may decrease the risk of cardiovascular and metabolic diseases. PMID- 26816668 TI - All-arthroscopic treatment of tibial avulsion fractures of the posterior cruciate ligament. AB - BACKGROUND: The posterior cruciate ligament (PCL) avulsion fracture from its tibial insertion is a rare condition. Despite the further technical advent in refixation of avulsion fractures, the reported failure rate of current approaches remains high and the optimal surgical technique has not been elucidated yet. The purpose of the current study is to present an all-inside arthroscopic reconstruction technique for bony tibial avulsion fractures of the PCL and initial clinical outcomes. METHODS: Patients underwent a thorough clinical and radiological examination of both knees at 3, 6, 12, 18, and if possible also at 24 months. Clinical evaluation included subjective and objective IKDC 2000, Lysholm score, and KOOS score. Radiographic imaging studies included CT scans for assessment of osseous integration and anatomic reduction of the bony avulsion. In addition to that posterior stress radiographs of both knees using the Telos device (Arthrex, Naples, USA) were conducted to measure posterior tibial translation. RESULTS: A total of four patients (1 female, 3 male; o 38 (+/- 18) years), who underwent arthroscopic refixation of a PCL avulsion fracture using the Tight Rope device were enrolled in this study. Mean follow up was 22 [18-24] months. The mean subjective IKDC was 72.6% (+/- 9.9%). Regarding the objective IKDC three patients accounted for grade A, one patient for grade C. The Lysholm score yielded 82 (+/- 6.9) points. The KOOS score reached 75% (+/- 13%; symptoms 76%, pain 81%, function 76%, sports 66%, QoL 64%). All patients showed complete osseous integration and anatomic reduction of the bony avulsion. The mean posterior tibial translation at final follow up was 2.8 [0-7] mm. CONCLUSIONS: All-arthroscopic treatment of tibial avulsion fractures of the posterior cruciate ligament provides satisfactory clinical results in a preliminary patient cohort. It is a reproducible technique, which minimizes soft tissue damage and obviates a second surgery for hardware removal. Further clinical studies with larger patient cohorts and a control group are needed to further confirm these preliminary results. PMID- 26816667 TI - Current concepts review: Fractures of the patella. AB - Fractures of the patella account for about 1% of all skeletal injuries and can lead to profound impairment due to its crucial function in the extensor mechanism of the knee. Diagnosis is based on the injury mechanism, physical examination and radiological findings. While the clinical diagnosis is often distinct, there are numerous treatment options available. The type of treatment as well as the optimum timing of surgical intervention depends on the underlying fracture type, the associated soft tissue damage, patient factors (i.e. age, bone quality, activity level and compliance) and the stability of the extensor mechanism. Regardless of the treatment method an early rehabilitation is recommended in order to avoid contractures of the knee joint capsule and cartilage degeneration. For non-displaced and dislocated non-comminuted transverse patellar fractures (2 part) modified anterior tension band wiring is the treatment of choice and can be combined - due to its biomechanical superiority - with cannulated screw fixation. In severe comminuted fractures, open reduction and fixation with small fragment screws or new angular stable plates for anatomic restoration of the retropatellar surface and extension mechanism results in best outcome. Additional circular cerclage wiring using either typical metal cerclage wires or resorbable PDS/non resorbable FiberWires increases fixation stability and decreases risk for re dislocation. Distal avulsion fractures should be fixed with small fragment screws and should be protected by a transtibial McLaughlin cerclage. Partial or complete patellectomy should be regarded only as a very rare salvage operation due to its severe functional impairment. PMID- 26816669 TI - Current diagnostics and treatment of the cubital tunnel syndrome in Austria. AB - According to the vote of the Austrian Society for Surgery of the Hand (OGH) an investigation to collect data on the current state of the treatment of cubital tunnel syndrome was initiated. Over one year a total of 875 patients with cubital tunnel syndrome were operated in Austria, this means an incidence of this nerve entrapment of 0.011%. Most of the operations were done by trauma surgeons (287; 33%). For diagnosis most of the centers rely on clinical symptoms, electroneurophysiology, and elbow X-ray. 40% of the institutions regard conservative therapy as useless and not indicated. If conservative treatment modalities are applied, physiotherapy (97%), non-steroidal anti-inflammatory medication (77%), and glucocorticoid injections (30%) are primarily used. In case of simple nerve entrapment most of the surgeons (72%) prefer simple nerve decompression. If there is additional pathology subcutaneous cubital nerve transposition is recommended (62%). Endoscopic techniques are only use by 3% of the surgeons. In the postoperative care, physiotherapy is favored in 51%, whereas 24% do not judge any postoperative care as beneficial. The three most often encountered complications were incomplete remission, scar contracture and hypertrophy, and postoperative bleeding. PMID- 26816666 TI - Hyperglycemic Stress and Carbon Stress in Diabetic Glucotoxicity. AB - Diabetes and its complications are caused by chronic glucotoxicity driven by persistent hyperglycemia. In this article, we review the mechanisms of diabetic glucotoxicity by focusing mainly on hyperglycemic stress and carbon stress. Mechanisms of hyperglycemic stress include reductive stress or pseudohypoxic stress caused by redox imbalance between NADH and NAD(+) driven by activation of both the polyol pathway and poly ADP ribose polymerase; the hexosamine pathway; the advanced glycation end products pathway; the protein kinase C activation pathway; and the enediol formation pathway. Mechanisms of carbon stress include excess production of acetyl-CoA that can over-acetylate a proteome and excess production of fumarate that can over-succinate a proteome; both of which can increase glucotoxicity in diabetes. For hyperglycemia stress, we also discuss the possible role of mitochondrial complex I in diabetes as this complex, in charge of NAD(+) regeneration, can make more reactive oxygen species (ROS) in the presence of excess NADH. For carbon stress, we also discuss the role of sirtuins in diabetes as they are deacetylases that can reverse protein acetylation thereby attenuating diabetic glucotoxicity and improving glucose metabolism. It is our belief that targeting some of the stress pathways discussed in this article may provide new therapeutic strategies for treatment of diabetes and its complications. PMID- 26816670 TI - Cheilitis glandularis: Case report with respect to immunohistochemical findings. AB - Cheilitis glandularis (CG) is a rare benign affection of the lip mucosa. The etiology and pathogenesis of CG are unknown. Surgical measures are the leading therapeutic options to treat CG. This case report on a 55-year-old female illustrates the recurrent affection of the lips over several years and local therapy. Furthermore, the study of the resected glands intends to differentiate the lesions with respect to the recently introduced concept of immunoglobulin G4 related diseases. PMID- 26816671 TI - Reducing morbidity with surgical adhesives following inguinal lymph node dissections for the treatment of malignant skin tumors. AB - BACKGROUND: Inguinal lymph node dissection (ILND) is associated with a high rate of morbidity. To evaluate the clinical benefit of surgical adhesives to reduce complications in patients undergoing ILND, we compared the use of TissuGlu((r)) Surgical Adhesive and ARTISS((r)) fibrin sealant with a control population. MATERIAL AND METHODS: We conducted a retrospective analysis of patients undergoing ILND for metastatic malignant skin tumors at one hospital, Fachklinik Hornheide (Munster, Germany), from January 2011 through September 2013, assessing 137 patients with a total of 142 procedures. RESULTS: Complications occurred in 22/60 procedures in the TissuGlu group (TG), in 8/17 in the ARTISS group (AG), and in 29/65 in the control group (CG). Prolonged drainage and seroma were recorded in 16 (26.7%), four (23.5%), and 26 (40%) respectively (non significant). TG showed less extended drainage vs. CG (p=0.082). Mean daily drain volumes were significantly lower in AG vs. CG (p=0.000). With regard to wound infection, there was a 15% reduction in TG and 74% increase in AG group. Revision surgery was reduced by 36% in TG and increased by 54% in AG. Mean daily drain volumes were significantly lower in AG vs. CG (p=0.000). Mean total post operative drain volume was lower in TG and AG vs. CG (p<0.001 among groups, CG vs. TG p<0.001, CG vs. AG p<0.001). The mean body mass index (BMI) was significantly higher in patients with complications, 29.4+/-5.8 vs. 25.3+/-4.1 (p=0.000). CONCLUSION: The use of TissuGlu in our ILND patients was associated with a reduction in post-operative wound related complications and the need for revision surgeries compared to the control group. Daily drainage was significantly lower within the first 7 post-operative days with the use of ARTISS, but the benefit was lost due to the higher occurrence of wound infection and revision surgery. BMI above 29 is a risk factor for complications following ILND. ( LEVEL OF EVIDENCE: level IV, retrospective case study). PMID- 26816672 TI - Protocol for the prevention and management of complications related to ADM implant-based breast reconstructions. AB - Acellular dermal matrix (ADM) implant-based reconstructions have transformed direct-to-implant breast reconstruction (DTI). But like all surgery, it is not deplete of complications such as seroma, infections and wound healing problems. These are cited with varying frequencies in the literature. With increased experience and through a series of measures instituted to minimize complications, we have been able to improve outcomes for our patients. We report our technical refinements for prevention of ADM reconstruction associated complications including patient selection, implant selection, drains, dressing and our post operative antibiotic regime. We also outline our protocol for the management of ADM associated complications including seroma, simple and complex infection and red breast syndrome, such that the sequelae of complications are minimized and patients achieve a better long-term outcome. PMID- 26816674 TI - Pediatric Laparoscopic Surgery in Pakistan. PMID- 26816673 TI - Indications and the requirements for single-use medical gloves. AB - AIM: While the requirements for single-use gloves for staff protection are clearly defined, the conventional medical differentiation between "sterile surgical gloves" used during surgical procedures and "single-use medical gloves" used in non-sterile medical areas does not adequately define the different requirements in these two areas of use. Sterilization of single-use medical gloves is not performed if sterility is not required; thus, another terminology must be found to identify the safety quality of non-sterile single-use medical gloves. Therefore, the labeling of such gloves should reflect this situation, by introducing the term "pathogen-free" single-use glove. The hygienic safety of such a glove would be attainable by ensuring aseptic manufacturing conditions during manufacturing and control of pathogen load of batch controls after fabrication. Proposed recommendation: Because single-use gloves employed in non sterile areas come into contact not only with intact skin but also with mucous membranes, no potential pathogens should be detectable in 100 mL of rinse sample. In order to declare such gloves as pathogen-free we suggest absence of the indicator species S. aureus and E. coli. In addition, the total CFU count should be evaluated, since a high load indicates lack of optimal hygiene during the manufacturing process. Based on the requirements for potable water and findings obtained from investigations of the bacterial load of such gloves after manufacturing, the here suggested limit for the total bacterial count of <10(2) CFU/mL of rinse sample per glove seems realistic. PMID- 26816675 TI - Synchronous Ipsilateral Wilms' Tumor and Neuroblastoma in an Infant. AB - Wilms' tumor (WT) and neuroblastoma (NB), the two most common extra-cranial solid malignant tumors, are seldom seen together in the same patient. A 10-month girl presented with a right retroperitoneal mass. A preoperative diagnosis of Wilms' tumor (WT) was made. She was given preoperative chemotherapy followed by surgery. At surgery a renal mass (WT) and a suprarenal mass (neuroblastoma - NB) were removed. She finally succumbed to metastatic NB in the postoperative period. PMID- 26816676 TI - Video Assisted Anal Fistula Treatment in a Child with Perianal Fistula. AB - Perianal fistula formation is a rare complication in children after rectal biopsy. Perianal fistula may become difficult to treat; therefore a lot of surgical options are present. One of these options is video assisted anal fistula treatment (VAAFT). We present a 6-year-old female who developed perianal fistula following rectal biopsy for which VAAFT was done successfully. PMID- 26816677 TI - Herlyn-Werner-Wunderlich Syndrome: A Rare Cause of Pelvic Pain and High CA 19-9 Levels in an Adolescent Girl. AB - Herlyn-Werner-Wunderlich (HWW) syndrome is a rare developmental anomaly that includes uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis. A 13-year-old girl presented with chronic abdominal pain. Magnetic resonance imaging revealed uterus didelphys, hematometrocolpos and renal agenesis on the right side with imperforate hymen. Subsequently the patient was found to have Mullerian duct anomalies. CA 19-9 level was high. At laparoscopy combined with vaginoscopy hematocolpos was drained following which she improved clinically and CA 19-9 level returned to normal. PMID- 26816678 TI - Tuberculosis of the Thyroid in a Child: A Rare cause of Thyromegaly. AB - Tuberculosis of thyroid gland is extremely rare in children. We describe the case of a 6-year girl child, presenting with a multinodular thyroid swelling. Fine needle aspiration cytology showed extensive necrosis with few epithelioid cell granulomas and occasional acid-fast bacilli, suggesting a diagnosis of tuberculosis. The child was put on anti-tuberculous drugs with significant improvement. Tuberculosis of the thyroid gland, although rare, should be considered in differential diagnosis of thyroid swelling, especially in endemic areas. PMID- 26816679 TI - Gastric Duplication Cyst in Association with Duodenal Atresia in a Neonate. AB - Concurrence of duodenal atresia and gastric duplication cyst is extremely rare entity. We report a 6-day-old female neonate who presented with neonatal intestinal obstruction. X-ray abdomen showed double bubble sign. At laparotomy, a huge cystic structure attached to greater curvature of the stomach along with duodenal atresia of second part of duodenum was found. The cystic structure was excised and duodeno-duodenostomy performed. Histopathology report confirmed it gastric duplication cyst. PMID- 26816680 TI - Spontaneous Gastric Perforation in a Case of Collagenous Gastritis. AB - Collagenous gastritis is an extremely rare disease, both in children and adults. Symptoms vary depending on the extent of collagenous changes in the bowel. In most of the children, iron deficiency anemia and abdominal pain are the presenting symptoms. We present a 15-year-old boy with acute abdomen due to gastric perforation the cause of which was collagenous gastritis. PMID- 26816681 TI - Gastrointestinal Autonomic Nerve Tumor of the Colon: A Rare Cause of Persistent Abdominal Pain in a Child. AB - Gastrointestinal autonomic nerve tumor (GANT) is extremely rare and considered a variant of gastrointestinal stromal tumors (GISTs). GANT originates from the intestinal autonomic nervous system mostly of small intestine or the stomach. We report a colonic GANT diagnosed in a 5-year-old child who presented with abdominal pain and fever for a long period. Colonic resection and end to end anastomosis proved curative without the need of chemo-radiotherapy. Given the rarity of the tumor, the patient is on our long term follow-up. PMID- 26816682 TI - Angiomyxoma in Accessory Hepatic Lobe. PMID- 26816683 TI - Introduction to the inaugural issue of TAU. PMID- 26816684 TI - What's new in urological trauma? 2012 update. PMID- 26816685 TI - The efficacy of resiniferatoxin in prevention of catheter related bladder discomfort in patients after TURP - a pilot, randomized, open study. AB - BACKGROUND: Resiniferatoxin (RTX) has been shown to have variable efficacy in the treatment of intractable lower urinary tract symptoms and symptoms associated with neurogenic detrusor overactivity. It has also been used successfully in treating overactive bladder (OAB). In order to evaluate the potential and efficiency of RTX in treatment of catheter related bladder discomfort (CRBD) over post-operative period of transurethral resection of the prostate (TURP), we conducted the current pilot, randomized open study. METHODS: The study was comprised of 48 patients undergoing TURP in a single institute from September 2007 to September 2008. Patients were randomly divided into Group-RTX and Group control. CRBD was classified into 4 degrees: degree 0, 1, 2, and 3. Patients with the most severed CRBD (degree-3) were treated with tolterodine. RESULTS: There were no statistical difference of patients' age, prostate volume, IPSS score, storage score and void score in IPSS, and QOL score between the two study groups(P=0.213, 0.356, 0.471, 0.554, 0.055 and 0.380, respectively). RTX pre treatment reduced incidence of CRBD. 25% of the patients in RTX group had CRBD, at 6 hours/1 day and 3 days after TURP, significantly lower than the control group in which 75% of the patients during the same period (P=0.001). During the three days post-operative period, RTX also reduced severity of CRBD, compared with the control group. No patient in Group RTX sufferred CRBD of degree 3, a clear contrast to the control group in which 7 patients had degree 3 CRBD, during three days post-operative. Finally, less patients in RTX group required tolterodine, compared with control, P=0.009. Interestingly, the difference of CRBD incidence between Group RTX (50%) and control (75%) diminished 5 days after TURP, P=0.135. CONCLUSIONS: Pretreatment with intravesical resiniferatoxin significantly reduces the incidence and severity of catheter related bladder discomfort in patients after TURP. PMID- 26816686 TI - Neuromodulation and neurostimulation: overview and future potential. PMID- 26816688 TI - The aging penis: what is it trying to tell us? PMID- 26816687 TI - Coining a new term-Urovesicology: advancing towards a mechanistic understanding of bladder symptoms. PMID- 26816689 TI - Randall plaque versus renal stone? PMID- 26816690 TI - Design and construction of translational medicine platform for urologic oncology. AB - Translational medicine is a new medical model which focus on overcoming the serious imbalance among the basic research, its clinical and public health application. Its core is to establish effective ties among basic medical researchers, public health workers and doctors who know the needs of patients, particularly translating the molecular medical research results to suitable disease prevention, diagnosis, treatment and prevention methods effectively. This paper discusses the design and construction of the translational medicine platform for urologic system tumors. However, there is no draw on the precedent, it is a challenging project to create such a complicated platform and make it running smoothly and effectively. Based on the Tianjin Translational Medicine Platform for Urologic Oncology (TTMPUO) which had been established in support of Tianjin Science and Technology Commission, this paper will focus on describing the design ideas and the essential parts of the platform. PMID- 26816691 TI - Predicting the future of urodynamics. PMID- 26816692 TI - Systemic implications of urinary stone disease. AB - Urinary stone disease is the third most common condition affecting the urinary tract. It contributes to a great deal of morbidity for both men and women, and cost the United States (US) over 5.3 billion dollars in 2000 alone. Moreover, it is associated with systemic diseases such as hypertension, diabetes, and other components of the metabolic syndrome. Reciprocally, these systemic diseases may be contributing to the rising incidence in urinary stone disease. Previously described mechanisms of stone formation attribute stone development and growth to the urinary milieu. While this may partly influence the process, it cannot account for the associations between systemic diseases and stones observed in large community-based studies. Here we present a review of the evidence demonstrating a link between urinary stone disease and components of the metabolic syndrome. We believe a vascular etiology for the initiation of urinary stones may tie these processes together. PMID- 26816693 TI - Mast cells, estrogens, and cryptorchidism: A histological based review. AB - If untreated, cryptorchidism leads to age dependent decreases in germ cell number (GCN) and testicular fibrosis. The pathophysiology of this process and its long term effects on fertility are unclear. Mast cells are intricately involved in inflammation and fibrosis in a variety of organ systems. Their secretory products have mitogenic effects on fibroblasts and promote collagen deposition. Mast cell activation and migration are under the influence of estrogens and this interaction has been demonstrated in the testes in several animal models. Models of cryptorchidism have shown increased estrogen levels and expression of estrogen receptors in undescended testes compared to controls. Mast cell numbers have positively correlated with testicular fibrosis in human studies and decreased spermatogenesis as well. We found no human studies of mast cells in cryptorchid testes. However several animal models have investigated the effect of estrogens on mast cells and spermatogenesis in undescended testes. In this review we examine the possible links between estrogens, mast cells, and testicular fibrosis in cryptorchidism, focusing on histological studies. PMID- 26816694 TI - Phalloplasty for the genetic male. AB - The goal of total phallic reconstruction in the genetic male is the creation of a sensate and cosmetically acceptable phallus with an incorporated neo-urethra that allows the patient to void while standing, engage in penetrative sexual intercourse with confidence and ejaculate in the vagina. PMID- 26816695 TI - Commentary on high flow, non-ischemic, priapism. PMID- 26816696 TI - Denosumab: Delay of bone metastasis in men with nonmetastatic castrate-resistant prostate cancer. PMID- 26816697 TI - Extension of the therapeutic spectrum in castration-resistant prostate cancer: Osteoclast inhibition with denosumab. PMID- 26816698 TI - Modifying sunitinib schedule in advanced kidney cancer patients: Reflections from the results of the renal EFFECT trial. PMID- 26816699 TI - Milestones for development of tivozanib for kidney cancer therapy. PMID- 26816700 TI - Erectile dysfunction: Doctors' perspectives on patients' concerns. PMID- 26816701 TI - PIVOT and the challenges of localized prostate cancer care. PMID- 26816702 TI - New prognostic models in metastatic renal cancer. PMID- 26816703 TI - Interpretation of PIVOT findings. PMID- 26816704 TI - Does normalizing PSA after successful treatment of chronic prostatitis with high PSA value exclude prostatic biopsy? AB - OBJECTIVE: Evaluate male patients with diagnosed chronic prostatitis, elevated serum prostate-specific antigen (PSA) to find out whether medical treatment with antibiotics and anti-inflammatory drugs can lower serum PSA, and consequently decrease the prostate cancer detection rate in patients with post-treatment PSA<4 ng/mL. MATERIALS AND METHODS: This prospective study evaluated 142 male patients aged 40-73 years whose presented with elevated serum PSA>4 ng/mL and were consequently diagnosed with chronic prostatitis as expressed prostatic excretions examination revealed more than 10 white blood cells per high power field. The Patients underwent treatment with antibiotics and nonsteroidal anti-inflammatory agents for 6-weeks. Subsequently, all patients are Followed-up by serum PSA and performed transrectal ultrasonography-guided prostate biopsy within 2 months of treatment. RESULTS: Mean patient age was (54.4+/-13.5) years. The mean PSA pretreatment was (8.11+/-3.7) ng/mL and after treatment, the mean PSA denoted a significant decrease to (4.7+/-3.5) ng/mL (P=0.002). The percent of changes in mean PSA was 41.9%. Prostatic biopsy after treatment showed that, cancer prostate in 31 patients (21.8%), chronic prostatitis in 71 patients (50.7%), chronic prostatitis plus benign prostatic hyperplasia (BPH) in 31 (21.8%) and BPH in 9 patients (6.3%) With regard to PSA values, cancer prostate patients were 3/25 (12%) if PSA<2.5 ng/mL, 6/47 (12.7%) if 4.0>PSA>=2.5 and 21/70 (30%) if PSA>=4.0. The numbers of cancer prostate detected patients were 30 (21.1%). CONCLUSIONS: Chronic prostatitis is one of the causes that elevate serum PSA levels. Treatment of chronic prostatitis with elevated PSA by antibiotics and anti-inflammatory agents can decrease the elevated PSA to the normal levels. Nevertheless, the opportunities of potential prostate cancer still exist in patients with a decreased PSA level even also if PSA<2.5 ng/mL. PMID- 26816705 TI - Vesicoureteral reflux and bladder dysfunction. AB - The relationship between vesicoureteral reflux and bladder dysfunction is inseparable and has long been emphasized. However, the primary concern of all physicians treating patients with vesicoureteral reflux is the prevention of renal scarring and eventual deterioration of renal function. Bladder dysfunction, urinary tract infection and vesicoureteral reflux are the three important factors which are closely related to each other and contribute to the formation of renal scar. Especially, there is ongoing discussion regarding the role of bladder dysfunction in the prognosis of both medically and surgically treated vesicoureteral reflux. The effect of bladder dysfunction on VUR is mostly via inadequate sphincter relaxation during infancy which is closer to immature bladder dyscoordination rather than true dysfunction. But after toilet training, functional obstruction caused by voluntary sphincter constriction during voiding is responsible through elevation in bladder pressure, thus distorting the architecture of bladder and ureterovesical junction. Reports suggest that voiding phase abnormalities in lower urinary tract dysfunction contributes to lower spontaneous resolution rate of VUR. However, filling phase abnormalities such as involuntary detrusor contraction can also cause VUR even in the absence of dysfunctional voiding. With regards to the effect of bladder dysfunction on treatment, meta-analysis reveals that the cure rate of VUR following endoscopic treatment is less in children with bladder bowel dysfunction but there is no difference for open surgery. The pathophysiology of bladder dysfunction associated with UTI can be explained by the 'milk-back' of contaminated urine back into the bladder and significant residual urine resulting from functional outlet obstruction. In addition, involuntary detrusor contraction can decrease perfusion of the bladder mucosa thus decreasing mucosal immunity and creating a condition prone to UTI. In terms of renal scarring, dysfunctional voiding seems to be more closely related to renal damage in association with VUR than overactive bladder. However, studies show that UTI can induce renal scarring even without VUR present and urodynamic abnormalities are quite often detected in these cases. Whether reflux of sterile urine in bladder dysfunction can cause significant renal scarring, especially when intrarenal reflux is present remains controversial. Another issue that warrants further research is the direct relationship between bladder dysfunction and renal scarring, since some reports suggest that these two conditions share a common genotype. Recently some studies have suggest VUR as a causal factor of bladder dysfunction, supported by the fact that bladder dysfunction resolves after injection therapy of VUR. Further study with more objective evaluation of bladder dysfunction may be needed. PMID- 26816706 TI - Regenerative technology for future therapy of erectile dysfunction. PMID- 26816708 TI - Could tivozanib be a new potent pan-VEGF inhibitor in RCC therapy? PMID- 26816707 TI - Phytotherapy: emerging therapeutic option in urologic disease. AB - Phytotherapy belongs to the area of complementary and alternative medicine (CAM) and the definition of phytotherapy is the use of plants or plant extracts for medicinal uses. Interest in phytotherapy is growing in both Asian and western countries for its use in the prevention and management of disease, improvement of general health and anti-aging. And also, there are several studies about the efficacy of phytotherapy in urologic diseases like benign prostatic hyperplasia (BPH), erectile dysfunction (ED), late-onset hypogonadism (LOH) and infertility in males. Phytotherapy for BPH including saw palmetto, pygeum, and nettles, is under vigorous research for the therapeutic effect. No solid evidence showing better effective treatment modality for ED than placebo has been found yet for phytotherapy. Recently, a potent NO donor, L-arginine is under research with promising results. Phytotherapy is used by a number of patients with urological disease, and urologists need to have accurate knowledge about phytotherapy as well as keep a cautious approach. The possible effects and side effects should be defined and related to urologic patients by urologists. PMID- 26816709 TI - The complexity of sunitinib dosing in renal cell cancer patients. PMID- 26816710 TI - Tivozanib: is total VEGFR inhibition the way to success in terms of tolerability and efficacy in advanced kidney cancer? PMID- 26816711 TI - Yinglu Guo: PSA screening test requires wider application in China. PMID- 26816712 TI - Complete remission with tyrosine kinase inhibitors in renal cell carcinoma. PMID- 26816713 TI - Assessment of risk factors of pediatric urolithiasis in Egypt. AB - OBJECTIVE: Pediatric urolithiasis is a significant medical problem, which has seen an increasing incidence in developing countries. The main objective of the present study was to investigate the clinical characteristics and the most important risk factors that contribute to stone formation in Egyptian children. PATIENTS AND METHODS: This prospective study was carried out at the outpatient clinics of Cairo university children's hospital as well as October 6 University hospitals, between November 2008 and March 2012. One hundred and fifty children (100 males, 50 females; mean age 3.5 years; range, 1-14 years) suffering from urinary stones were included. The mean follow-up duration; 33.1 months. All patients underwent detailed medical and family histories, dietary habits and physical examination, including Growth percentiles. Laboratory investigations were performed including: complete urine analysis and culture and sensitivity tests, urine collection in 24-h to quantity urinary volume, pH, calcium, uric acid, magnesium, creatinine, oxalate and citrate. Blood samples were obtained to measure (serum creatinine, calcium, phosphorus, uric acid level, and alkaline phosphatase and electrolyte levels, in addition to pH and pCO2 values). Radio sonographic investigation of the abdomen and pelvis was also performed. RESULTS: The commonest presentations were abdominal pain in 42 children (28%) and gross hematuria in 35 patients (23%). Urinary tract infection was the most common risk factor, 60 patients (40%) had UTI, 70% of them had recurrent infections. Genito urinary abnormalities, as a risk factor, were detected in 38 children (25%), with vesico-uretheral refux being the commonest abnormality (18/38). Metabolic risk factors were detected in 34 children (23%) with hypercalciuria and hyperoxaluria being the commonest metabolic abnormalities. Treatments used were, ESWL in 69 patients (46%), endoscopic interventions in 40 children (27%) and open surgery in 15 children (10%). The remaining 26 children (17%) were managed conservatively. CONCLUSIONS: treatment of pediatric urolithiasis requires stone removal besides a thorough metabolic and environmental evaluation of all patients on an individual basis, entailing the treatment of metabolic abnormalities. Children with a positive family history should be followed up cautiously to avoid stone recurrence. PMID- 26816714 TI - Biomarkers for tyrosine kinase inhibitors in renal cell cancer. PMID- 26816715 TI - Complications associated with percutaneous nephrolithotomy. PMID- 26816716 TI - Commentary on the myths of Peyronie's disease. PMID- 26816717 TI - Micro-RNAs, next-generation molecular markers in male infertility field. PMID- 26816718 TI - Penile rehabilitation after radical prostatectomy: patients' attitude and feasibility in China. AB - OBJECTIVE: To investigate the behavior of Chinese erectile dysfunction (ED) patients after radical prostatectomy (RP) who were offered the penile rehabilitation and to assess their attitude and feasibility of rehabilitation after RP in China. MATERIALS AND METHODS: Comprehensive medical and sexual histories of 187 evaluable PCa patients for RP were obtained together with their attitude towards penile rehabilitation. The rehabilitation data was compared between patients who accepted this treatment or not. The successful intercourse rate six months after treatment was also compared among three rehabilitation interventions, including phosphodiesterase type 5 inhibitor (PDE-5i), vacuum erection device (VED) and combination of both. RESULTS: 141 (75.4%) patients reported being sexually active in the six months before RP.122 (65.2%) patients wished to preserve sexual activity and 80 (42.8%) had interest in penile rehabilitation after RP. Penile rehabilitation rate was 30.5%. The patients with younger age (P<0.001), higher IIEF-5 score preoperatively (P=0.03) and no adjuvant therapy post-RP (P=0.01) were more acceptable for rehabilitation. Main reasons for refusal of rehabilitation included lack of sexual interest followed by high cost of treatment. The successful intercourse rate was not significantly different among three rehabilitation interventions (P=0.32). CONCLUSIONS: Less than one-third of Chinese RP patients accepted penile rehabilitation postoperatively. Patients' attitude towards rehabilitation was conservative because of many reasons from traditional Chinese culture, doctors and patients themselves. Penile rehabilitation was feasible and effective in Chinese RP patients. PMID- 26816719 TI - Peyronie's disease: current therapy. PMID- 26816720 TI - Current rehabilitation strategy: clinical evidence for erection recovery after radical prostatectomy. AB - Erectile function (EF) recovery remains a prominent functional outcome underachievement of radical prostatectomy (RP), despite the success of anatomic "nerve-sparing" technique and its recent refinements in the modern surgical era. Delayed (for as much as a few years) or incomplete (partial and unusable) EF recovery commonly occurs in many men still today undergoing this surgery. "Penile rehabilitation", alternatively termed "EF rehabilitation", originated formally as a therapeutic practice approximately 15 years ago for addressing post-RP erectile dysfunction (ED) beyond conventional ED management. Although the premise of this therapy is conceptually sound and generally accepted, in reference to the implementation of strategies for promoting EF recovery to a naturally functional level in the absence of erectile aids (distinct from the premise of conventional ED management), the optimal manner and efficacy of currently suggested therapeutic strategies are far less established. Such strategies include regimens of standard ED-specific therapies (e.g., oral, intracavernosal, and intraurethral pharmacotherapies; vacuum erection device therapy) and courses of innovative interventions (e.g., statins, erythropoietin, angiotensin receptor blockers). An endeavor in evolution, erection rehabilitation may ideally comprise an integrative program of sexual health management incorporating counseling, coaching, guidance toward general health optimization and application of demonstrably effective "rehabilitative" interventions. Ongoing intensive discovery and rigorous investigation are required to establish efficacy of therapeutic prospects that fulfill the intent of post-RP erection rehabilitation. PMID- 26816721 TI - Anterior urethral stricture review. AB - Male anterior urethral stricture disease is a commonly encountered condition that presents to many urologists. According to a National Practice Survey of Board Certified Urologist in the United States most urologists treat on average 6-20 urethral strictures yearly. Many of those same urologists surveyed treat with repeated dilation or internal urethrotomy, despite continual recurrence of the urethral stricture. In point of fact, the urethroplasty despite its high success rate, is underutilized by many practicing urologists. Roughly half of practicing urologist do not perform urethroplasty in the United States. Clearly, the reconstructive ladder for urethral stricture management that was previously described in the literature may no longer apply in the modern era. The following article reviews the etiology, diagnosis, management and comparisons of treatment options for anterior urethral strictures. PMID- 26816722 TI - Peyronie's disease: contemporary review of non-surgical treatment. AB - BACKGROUND: Peyronie's disease (PD) remains a therapeutic dilemma for the treating physician. This is in spite of a large array of treatments which have been used since the time of de la Peyronie in the mid 18(th) century. Part of this problem is due to an incomplete understanding of the etiopathophysiology of this scarring disorder. Having a better understanding of the how and why the scarring occurs may help prevent progression, but ultimately reversing the existing scar remains the real challenge. METHODS: This review discusses the current non-surgical treatment options for Peyronie's disease. Published articles in peer-reviewed journals are used, recognizing that the majority of the published trials are compromised by being single-center studies without a placebo control. RESULTS: A variety of treatments options have emerged, most with limited and unreliable benefit, but a few treatments have shown a consistent albeit incomplete response rate. Could this suggest that all PD is not the same and that the heterogeneous nature of this scarring disorder may account for why some patients respond and others do not? Further investigation of this diverse response rate may yield insights into the pathophysiology of PD. In the meantime, there have been many oral treatments offered for PD. Currently the only scientifically sensible treatments appear to be pentoxifylline, L-arginine, and possibly the phosphodiesterase type-5 inhibitors. Intralesional injection has been used for many years. The current treatment options include verapamil and interferon, with reported benefit with respect to reduced deformity and improved sexual function. Intralesional clostridial collagenase is in the midst of phase 3 trial analysis by the FDA in the USA and may become the newest and only FDA approved treatment for Peyronie's disease. External mechanical traction therapy has also recently emerged as a technique to reduce curvature, recover lost length, enhance girth, and possibly obviate surgery. CONCLUSIONS: It appears at this time that there is no clear, reliable and effective non-surgical treatment for Peyronie's disease, but it does appear from the published literature that several of the available treatments can result in reduction of deformity, improved sexual function, and may at a minimum stabilize the disease process so that deformity does not get worse particularly during the acute phase of this scarring disorder. Combination therapy in an effort to create a synergy between the chemical effects of oral and injectable drugs with the mechanical effects of external traction therapy may provide the best opportunity today for reduction of deformity in the man with Peyronie's disease. PMID- 26816724 TI - A critical look at descriptive epidemiology of sexual dysfunction in Asia compared to the rest of the world - a call for evidence-based data. AB - Recently evidence-based medicine has been applied to comparative epidemiological papers regarding sexual dysfunction that have appeared in the literature. This review is intended to focus the readers on a validated and standardized methodological evidence-based process for preparing such articles. It reviews four key articles that have been published in the English language that have obtained a high evidence-based score for reliability that have included descriptive epidemiology of sexual dysfunctions in men and women in Asia compared to the rest of the world. These four papers are analyzed in detail in order to provide stress of what constitutes evidence-based studies in descriptive epidemiology for sexual function. As can be seen there has not yet been a perfect article that compares the prevalence of sexual function in Asia compared to the rest of the world since there are key methodological problems in the collection of the data. In addition, there is a paucity of incidence studies for sexual dysfunction in Asian populations. The readers are encouraged to use this data in preparation of future descriptive epidemiological studies that involve Asian countries. PMID- 26816723 TI - Premature ejaculation: do we have effective therapy? AB - INTRODUCTION: Premature ejaculation (PE) is the most common sexual dysfunction, with the majority of PE patients remaining undiagnosed and undertreated. Despite its prevalence, there is a current paucity of data regarding available treatment options and mechanisms. The objective of the current investigation is to review and summarize pertinent literature on therapeutic options for the treatment of PE, including behavioral/psychologic, oral pharmacotherapy, and surgery. METHODS: A pubmed search was conducted on articles reporting data on available treatment options for PE. Articles describing potential mechanisms of action were additionally included for review. Preference was given towards randomized, controlled trials, when available. RESULTS: PE remains an underdiagnosed and undertreated disease process, with limited data available regarding potential underlying mechanisms and long-term outcomes of treatment options. Psychological/behavioral therapies, including the stop-start, squeeze, and pelvic floor rehabilitation techniques have demonstrated improvements in short-term series, with decreased efficacy with additional follow-up. Topical therapies, which are commonly utilized result in prolonged intravaginal ejaculatory latency time (IELT) at the expense of potential penile/vaginal Hypothesia. Oral therapies similarly demonstrate improved IELTs with variable side effect profiles and include selective serotonin reuptake inhibitors (daily or on demand), phosphodiesterase-5 inhibitors, alpha-1 adrenergic antagonists, and tramadol. Alternative therapies such as acupuncture have shown benefits in limited studies. Surgery is not commonly performed and is not recommended by available guidelines. CONCLUSIONS: PE is a common condition, with limited data available regarding its underlying pathophysiology and treatment. Available therapies include topical, oral, behavioral/psychologic modification, or a combination thereof. Additional research is required to assess the optimal treatment strategies and algorithms as well as to better define the mechanisms for PE and its management. PMID- 26816725 TI - The science of vacuum erectile device in penile rehabilitation after radical prostatectomy. AB - INTRODUCTION: Radical prostatectomy (RP) is a standard surgical treatment for clinically localized prostate cancer. Erectile dysfunction (ED) and penile shrinkage are common complications. Vacuum Erectile Device (VED) therapy uses negative pressure to distend the corporal sinusoids and to increase blood inflow into the penis. It is the second most commonly used method for penile rehabilitation after RP. However, the underlying mechanisms are still unclear. This paper is designed to review the scientific evidences of VED therapy after RP and discuss the possible mechanisms. METHODS: We reviewed published papers of post-prostatectomy penile rehabilitation using VED. We analyzed the scientific evidences of VED therapy and discussed the possible underlying mechanisms. RESULTS: There are existing clinical evidences for VED therapy to improve ED and preserve penile size. Emerging basic scientific evidence is available and further study is still needed to understand the mechanisms at the molecular level. CONCLUSIONS: Current clinical evidences support the safety, tolerability, effectiveness and benefits of early VED therapy after RP. The available basic scientific evidences demonstrate that VED therapy for penile rehabilitation is achieved by increasing arterial inflow, anti-apoptotic, anti-fibrotic and anti hypoxia mechanisms. PMID- 26816726 TI - Strategies for maintaining penile size following penile implant. AB - INTRODUCTION: Loss of penile size is a common complaint that can negatively affect patient satisfaction rates following successful penile prosthetic implant surgery. OBJECTIVE: The aim of this review is to describe the various strategies that have been used to maintain penile length or girth after the insertion of a penile prosthetic implant. METHODS: An extensive systematic literature review was performed, based on a search of the PUBMED database for articles published between 2002 to 2012. The following key words were used: penile prosthesis, implant, penile length, size, penis, enhancement, enlargement, phalloplasty, girth, lengthening, and augmentation. Only English-language articles that were related to penile prosthetic surgery and penile size were sought. DISCUSSION: Based on the results of our search, strategies were classified into 3 groups based on the timepoint in relation to the primary penile prosthetic insertion surgery, which included pre-insertion, intraoperative and post-insertion. CONCLUSIONS: Strategies to preserve and potentially increase penile size are of great importance to all implanters. Besides traction therapies and surgeries to enhance perceived penile size, refinements in the surgical approach are simple ways to optimize penile length. A direct comparison of treatment outcomes evaluating the various approaches is not currently possible, owing to divergent study techniques. The implanting surgeon can best serve his patient by adopting a combination of different strategies that are individualized and specific to the patient's needs. PMID- 26816728 TI - Refining treatment for the men who need it: lessons from the PIVOT trial. PMID- 26816727 TI - Sexual function and male cancer. AB - Quality of life in general and sexual functioning in particular have become very important in cancer patients. Biological factors such as anatomic alterations, physiological changes and secondary effect of medical interventions may preclude normal sexual functioning even when sexual desire is intact. In spite of modern surgical techniques, improved chemotherapeutical drugs and sophisticated radiation techniques, still many patients complain of impaired sexual function after cancer treatment. A large number of instruments already exist to assess quality of life in cancer patients. It is important to standardize procedures and to use validated questionnaires. Collecting data on an ongoing basis before and long after treatment is mandatory, and control groups must be used. Patients should be offered sexual counselling and informed about the availability of therapies for sexual dysfunctions. In this paper we review the topic of sexual functioning after treatment (predominantly after radiotherapy) of the most common malignancies in men and give suggestions for treatment. PMID- 26816729 TI - Does patient-tailored immunotherapy pave the way for new renal cell carcinoma treatment perspectives? PMID- 26816730 TI - Immunotherapy in renal cell cancer: the more the merrier? PMID- 26816731 TI - Treatment of failed vasectomy reversal using a microsurgical two-layer anastomosis technique. AB - OBJECTIVE: To evaluate the application of a microsurgical two-layer anastomosis technique in the treatment of failed vasectomy reversal. METHODS: A microsurgical two-layer anastomosis was used in a series of 24 patients with confirmed anastomotic obstruction after previous vasectomy reversal. The patients were followed up for 9 months to 6 years, and the efficacy of the procedure was evaluated by regular seminal analysis and pregnancy records. The results were compared with those obtained from 34 patients who had received primary microsurgical vasovasostomy in our hospital using the same microsurgical technique. RESULTS: In the treatment group for failed vasectomy reversal patients, the postoperative patency rate was 87.5% (21/24), resulting in a pregnancy rate of 54.2% (13/24). In primary reversal group, the postoperative patency rate was 94.1% (32/34), resulting in a pregnancy rate of 67.6% (23/34). Both the patency and pregnancy rate were not significantly different between these two groups. CONCLUSIONS: The microsurgical vasovasostomy and vasoepididymostomy provided satisfactory patency rate and natural pregnancy rate for patients with a previous failed vasectomy reversal, which is comparable with the results of patients who had undergone primary procedure. PMID- 26816733 TI - Tivozanib: a novel VGFR inhibitor for kidney cancer. AB - Treatment of kidney cancer has changed over the past 10 years with the approval of several targeted agents. These drugs are given on a long term base and toxicity is an issue for most patients. Despite improvement compared to immunotherapy, most patients will progress on these drugs. There is a need for more portent and better tolerated drugs. Tivozanib is a potent pan VEGR specific inhibitor. In this phase II trial it gave interesting results with an overall median PFS throughout the study of 11.7 months (95% CI: 8.3-14.3 months) and an overall objective response rate of 24% (95% CI: 19-30%). "Off"-target toxicity was mild. PMID- 26816732 TI - VEGF is associated with the poor survival of patients with prostate cancer: a meta-analysis. AB - BACKGROUND: Vascular endothelial growth factor (VEGF) is considered as a prime mediator of angiogenesis, and has been implicated in carcinogenesis and metastasis. Various studies examined the relationship between VEGF overexpression with the clinical outcome in patients with prostate cancer, but yielded conflicting results. METHODS: Electronic databases updated to July 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between VEGF status and survival of patients with prostate cancer. Survival data were aggregated and quantitatively analyzed. RESULTS: We performed a meta-analysis of 9 studies that evaluated the correlation between VEGF overexpression and survival in patients with prostate cancer. Combined hazard ratios suggested VEGF overexpression had an unfavorable impact on overall survival (OS) [hazard ratio (HR) =1.54, 95% CI (confidence interval): 1.25-1.83], but not disease free survival (DFS) (HR=1.23, 95% CI: 0.99-1.47) in patients with prostate cancer. No significant heterogeneity was observed among all studies. CONCLUSIONS: VEGF overexpression indicates a poor prognosis for patients with prostate cancer. PMID- 26816734 TI - Identification of biomarkers in pazopanib treated patients with renal cell carcinoma. PMID- 26816735 TI - Current clinical challenges in prostate cancer. AB - Prostate cancer is the most common malignancy and the second leading cause of cancer death in men in the United States. Close to $12 billion are spent annually on the treatment of prostate cancer in the US alone. Yet still there remain tremendous controversies and challenges that exist in all facets of the disease. This review and discussion will focus on issues and challenges for clinicians and patients diagnosed with the disease. Appropriate risk stratification for men with newly diagnosed prostate cancer is an appropriate first step for all patients. Once risk-stratified, for those with low-risk of death, it is increasingly recognized that overtreatment creates an unnecessary burden for many patients. This is particularly evident when put in the context of competing comorbidities in an elderly population. For those with advanced or high-risk localized disease, under-treatment remains too common. For those with a high-risk of recurrence or failure following primary treatment, adjuvant or salvage therapies are an option, but how and when to best deploy these treatments are controversial. Recently, tremendous progress has been made for those with advanced disease, in particular those with metastatic castrate-resistant prostate cancer (mCRPC). Within the last 4 years, five novel FDA approved agents, acting through distinct mechanisms have been FDA approved for mCRPC. With the introduction of these new agents a host of new challenges have arisen. Timing, sequencing and combinations of these novel agents are welcomed challenges when compared with the lack of available therapies just a few years ago. In this summary of current clinical challenges in prostate cancer we review critical recent studies that have created or shifted the current paradigms of treatment for prostate cancer. We will also highlight ongoing issues that continue to challenge our field. PMID- 26816736 TI - Androgen receptor-mediated non-genomic regulation of prostate cancer cell proliferation. AB - Androgen receptor (AR)-mediated signaling is necessary for prostate cancer cell proliferation and an important target for therapeutic drug development. Canonically, AR signals through a genomic or transcriptional pathway, involving the translocation of androgen-bound AR to the nucleus, its binding to cognate androgen response elements on promoter, with ensuing modulation of target gene expression, leading to cell proliferation. However, prostate cancer cells can show dose-dependent proliferation responses to androgen within minutes, without the need for genomic AR signaling. This proliferation response known as the non genomic AR signaling is mediated by cytoplasmic AR, which facilitates the activation of kinase-signaling cascades, including the Ras-Raf-1, phosphatidyl inositol 3-kinase (PI3K)/Akt and protein kinase C (PKC), which in turn converge on mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) activation, leading to cell proliferation. Further, since activated ERK may also phosphorylate AR and its coactivators, the non-genomic AR signaling may enhance AR genomic activity. Non-genomic AR signaling may occur in an ERK independent manner, via activation of mammalian target of rapamycin (mTOR) pathway, or modulation of intracellular Ca(2+) concentration through plasma membrane G protein-coupled receptors (GPCRs). These data suggest that therapeutic strategies aimed at preventing AR nuclear translocation and genomic AR signaling alone may not completely abrogate AR signaling. Thus, elucidation of mechanisms that underlie non-genomic AR signaling may identify potential mechanisms of resistance to current anti-androgens and help developing novel therapies that abolish all AR signaling in prostate cancer. PMID- 26816737 TI - Translating insights of AR signaling from mouse models. AB - Androgen receptor (AR) signaling plays a critical role in the physiology of the prostate and thus the biology of prostate cancer. Agents targeting the AR pathway have been the mainstay of treatment for patients with locally advanced and metastatic prostate cancer. In this review we will cover the role of androgen signaling in prostate cancer mouse models with an emphasis on how tumorigenic molecular alterations impact response to AR pathway inhibition and downstream AR target gene expression. Both of these concepts have meaningful implications for the management of patients with prostate cancer. PMID- 26816738 TI - Cancer stem cells in prostate cancer. AB - Prostate cancer (P-Ca) remains a leading cause of cancer-related death in men. Lately, increasing evidence for a hierarchically organized cancer stem cell (CSC) model emerged for different tumors entities, including P-Ca. CSCs are defined by several characteristics including self-renewal, pluripotency and tumorigenicity and are thought to be responsible for tumor recurrence, metastasis and cancer related death. In this review we discuss the recent research in the field of CSCs, its limitations and therapeutical implications in general and specifically in P-Ca. PMID- 26816740 TI - The argument for palliative care in prostate cancer. PMID- 26816739 TI - Novel non-AR therapeutic targets in castrate resistant prostate cancer. AB - Castrate resistant prostate cancer (CRPC) remains a disease with significant morbidity and mortality. The recent approval of abiraterone and enzalutamide highlight the improvements which can be made targeting the androgen receptor (AR) axis. Nonetheless, resistance inevitably develops and there is continued interest in targeting alternate pathways which cause disease resistance and progression. Here, we review non-AR targets in CRPC, with an emphasis on novel agents now in development. This includes therapeutics which target the tumour microenvironment, the bone metastatic environment, microtubules, cellular energetics, angiogenesis, the stress response, survival proteins, intracellular signal transduction, DNA damage repair and dendritic cells. Understanding the hallmarks of prostate cancer resistance in CRPC has led to the identification and development of these new targets. We review the molecular rationale, as well at the clinical experience for each of these different classes of agents which are in clinical development. PMID- 26816741 TI - Determinants of doctors' decisions to inquire about sexual dysfunction in Malaysian primary care settings. AB - BACKGROUND: Perceptions of how receptive men are to sexual health inquiry may affect Malaysian primary care doctors' decisions to initiate such a discussion with their male patients. This paper quantifies the impact of doctors' perceptions of men's receptivity on male sexual health inquiry. Sexual health inquiry is one of the five areas in a study on determinants of offering preventive health checks to Malaysian men. METHODS: This was a cross sectional survey among primary care doctors in Malaysia. The questionnaire was based on an empirical model defining the determinants of primary care doctors' intention to offer health checks. The questionnaire measured: (I) perceived receptivity of male patients to sexual health inquiry; (II) doctors' attitudes towards the importance of sexual health inquiries; (III) perceived competence and, (IV) perceived external barriers. The outcome variable was doctors' intention in asking about sexual dysfunction in three different contexts (minor complaints visits, follow-up visits and health checks visits). All items were measured on the Likert scale of 1 to 5 (strongly disagree/unlikely to strongly agree/likely) and internally validated. RESULTS: 198 doctors participated (response rate 70.4%). Female primary care doctors constituted 54.5%. 78% of respondents were unlikely to ask about sexual dysfunction in visits for minor complaints to their male patients, 43.6% in follow up visits and 28.2% in health checks visits. In ordinal regression analysis, positive perception of men's receptivity to sexual health inquiry significantly predicted the doctors' intention in asking sexual dysfunction in all three contexts; i.e., minor complaints visits (P=0.013), follow-up visits (P<0.0001) and health checks visits (P=0.002). Perceived competence in sexual health inquiry predicted their intention in the follow-up visits (P=0.006) and health checks visits (P<0.001). Lower cost to health checks only predicted their intention in the follow-up visits (P=0.010). CONCLUSIONS: Whilst sexual health inquiry should be initiated in an appropriate context, 'perceived receptivity' to sexual health inquiry significantly affected doctors' intention in initiating sexual health inquiry to their male patients. Malaysian men's health may be substantially improved by strategies that assist doctors to identify patient 'receptivity'. PMID- 26816742 TI - Acupuncture assisted local anesthesia for penile surgeries. AB - Although the mechanism of acupuncture for analgesia is not fully elucidated, a combination of acupuncture and several methods of topical blocks for local anesthesia has been effective to patients with indications for penile surgeries on ambulatory basis. We sought to review this unique clinical application since 1998. To summarize practice-based medical literature contingent this unique application and, in contrast, the commonly agreed either general or spinal anesthesia concerning those surgeries on this most sensitive organ-the delicate penis. From July 1998 to July 2013, total of 1,481 males underwent penile surgeries with specific topical nerve blockage in addition to acupuncture in which the acupoints of Hegu (LI4), Shou San Li (LI10), Quchi (LI11), and either Waiguan (TE5) or Neiguan (PC6) were routinely used. Careful anesthetic block of the paired dorsal nerve in the penile hilum associated with a peripenile infiltration was categorized to method I which is sufficient to anesthetize the penile structures for varied penile surgeries including 993 men of penile venous stripping surgeries, 336 cases of penile corporoplasty, 8 males of urethroplasty, 7 patients of vaso-vasostomy, 6 men of penile arterial reconstruction and 3 surgeries of penectomy. Whereas the bilateral cavernous nerve block and crural blockage were indispensably added up for anesthetizing the sinusoids of the corpora cavernosa (CC) for penile implant of varied model. It was allocated to method II and had been applied in 125 males. A further topical injection of the medial low abdominal region made it possible for implanting a three-piece model in three males. Thus recent discoveries and better understanding of the penile anatomy had been meaningful in the development and improvement of specific nerve blockade techniques for penile surgeries in particularly adding up with acupuncture techniques, while minimizing anesthetic adverse effects and resulting in a rapid return to daily activity with minimal complications. PMID- 26816744 TI - Innovative surgical techniques for managing Peyronie's disease: a video presentation. AB - Peyronie's disease is a disorder caused by fibrosis of the tunica albuginea, which results in penile deformity, pain, and can be associated with erectile dysfunction. Treatment options include a variety of medical and surgical approaches, with no clear consensus as to the best treatment option. Many medical therapies have been investigated, including oral, topical, injectable, and external-energy agents. Surgical management can involve plication with or without plaque resection, grafting procedures, or, in extreme cases, penile prosthesis implantation. Two of these treatment techniques are presented in a detailed technical review: the 16-dot plication and tunica-sparing plaque excision. PMID- 26816743 TI - Dapoxetine and the treatment of premature ejaculation. AB - BACKGROUND: Premature ejaculation (PE) is the most common male sexual complaint. Off-label oral selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for the treatment of PE. Dapoxetine is a short-acting SSRI specifically designed for on-demand use. The objective of this communication is to summarize the clinical and physiological evidence regarding the role of the serotonergic pathway and specifically dapoxetine in the treatment of PE. METHODS: A PubMed search was conducted on articles reporting data on dapoxetine for the treatment of PE. Articles describing the pathophysiology and treatment options for PE were additionally included for review. RESULTS: The etiology of PE is multi-factorial in nature. There are many treatment options for PE such as psychological/behavioral therapy, topical anesthetic agents, phosphodiesterase type 5 (PDE-5) inhibitors, and tramadol hydrochloride. SSRIs play a major role in PE treatment. Animal and clinical studies in addition to its pharmacokinetic document dapoxetine's clinical efficacy and safety for on-demand treatment of PE. CONCLUSIONS: Dapoxetine demonstrates clinical efficacy and a favorable side effect profile. Dapoxetine is currently the oral drug of choice for on-demand treatment of PE. PMID- 26816745 TI - Should perioperative anticoagulation be an integral part of the priapism shunting procedure? PMID- 26816746 TI - Virginia Johnson-human sexuality pioneer. PMID- 26816748 TI - Professor Christian G. Stief: the role of surgery for prostate cancer with bone metastases. PMID- 26816747 TI - Proposal of "cyclic therapy", a novel treatment strategy with targeted agents for advanced renal cell carcinoma. AB - The number of molecular targeted agents for advanced renal cell carcinoma (RCC) has gradually increased, but evidence on the optimal order of selection for such agents has not yet caught up with this trend. In addition, timing of switching molecular targeted drugs may also become an important issue for controlling the disease as types of these drugs grow in number. Based on the fact that the efficacy of a rechallenge of the drug previously used suggests the recovery of the sensitivity, a cyclic therapy in which drugs are changed before exacerbation to repeatedly administer several drugs in a rotated manner, may also be an effective sequential therapy. PMID- 26816749 TI - Medical treatment of male infertility. AB - The majority of male infertility is idiopathic. However, there are multiple known causes of male infertility, and some of these causes can be treated medically with high success rates. In cases of idiopathic or genetic causes of male infertility, medical management is typically empirical; in most instances medical therapy represents off-label use that is not specifically approved by the FDA. Understanding the hypothalamic-pituitary-gonadal (HPG) axis and the effect of estrogen excess is critical for the assessment and treatment of male infertility. The use of certain medical treatment has been associated with an increase in sperm production or motility, and primarily focuses on optimizing testosterone (T) production from the Leydig cells, increasing follicle-stimulating hormone (FSH) levels to stimulate Sertoli cells and spermatogenesis, and normalizing the T to estrogen ratio. PMID- 26816750 TI - Contemporary and future insights into fertility preservation in male cancer patients. AB - In recent years, survival rates of cancer patients have increased, resulting in a shift of focus from quantity to quality of life. A key aspect of quality of life is fertility potential; patients suffering from iatrogenic infertility often become depressed. Since many cancer therapies-chemotherapy, radiotherapy and/or surgery-and even cancer itself have detrimental effects on the male reproductive system, it is important to preserve fertility before any treatment commences. Currently, the only reliable method of male fertility preservation is sperm banking. For patients who are unable to provide semen samples by the conventional method of masturbation, there are other techniques such as electroejaculation, microsurgical epididymal sperm aspiration and testicular sperm extraction that can be employed. Unfortunately, it is presently impossible to preserve the fertility potential of pre-pubertal patients. Due to the increasing numbers of adolescent cancer patients surviving treatment, extensive research is being conducted into several possible methods such as testicular tissue cryopreservation, xenografting, in vitro gamete maturation and even the creation of artificial gametes. However, in spite of its ease, safety, convenience and many accompanying benefits, sperm banking remains underutilized in cancer patients. There are several barriers involved such as the lack of information and the urgency to begin treatment, but various measures can be put in place to overcome these barriers so that sperm banking can be more widely utilized. PMID- 26816751 TI - Ejaculatory physiology and pathophysiology: assessment and treatment in male infertility. AB - Azoospermia is a heterogeneous condition with multiple etiologies and a variety of treatments. In this chapter we present a summary of retrograde ejaculation and anejaculation, both of which are characterized by an absence of antegrade semen propulsion through the male reproductive tract. Each of these affects fertility, but is pathophysiologically distinct disorders with differing evaluation and treatment. Retrograde ejaculation has a myriad of well-characterized causes, from pharmacologic disruption to interference of neural mechanisms by surgical intervention for a variety of diseases. Medication is the mainstay of treatment, although only a minority responds and develops antegrade ejaculation. For the men who are not responders to medical therapy, but still have fertility goals, there are a variety of sperm retrieval techniques to assist their reproductive abilities. Failure of emission is characterized by an absence of the emission phase and no antegrade or retrograde expulsion of ejaculatory products. If fertility is desired, these men must rely on assisted ejaculatory procedures, and treatment choice is guided by etiology and response. Ultimately, retrograde ejaculation and failure of emission are in a spectrum of ejaculatory disorders which impair male fertility. PMID- 26816752 TI - Androgen deficiency and metabolic syndrome in men. AB - Metabolic syndrome (MetS) is a growing health concern worldwide. Initially a point of interest in cardiovascular events, the cluster of HTN, obesity, dyslipidemia, and insulin resistance known as MetS has become associated with a variety of other disease processes, including androgen deficiency and late-onset hypogonadism (LOH). Men with MetS are at a higher risk of developing androgen deficiency, and routine screening of testosterone (T) is advised in this population. The pathophysiology of androgen deficiency in MetS is multifactorial, and consists of inflammatory, enzymatic, and endocrine derangements. Many options for the concomitant treatment of both disorders exist. Direct treatment of MetS, whether by diet, exercise, or surgery, may improve T levels. Conversely, testosterone replacement therapy (TRT) has been shown to improve MetS parameters in multiple randomized controlled trials (RTCs). PMID- 26816753 TI - The role of animal models in the study of varicocele. AB - Varicocele is the most common correctible cause of male infertility and is present in 15% to 20% of the male population. Despite its prevalence, the pathophysiology of varicocele remains under investigation. One of the largest obstacles in studying varicocele is that it is almost exclusively found in humans. This has necessitated the creation of an animal model of varicocele. The most commonly used animal model involves the creation of a varicocele in a rodent by partially occluding the left renal vein. This model has provided a significant amount of data on varicocele, and a modification of this model utilizing microsurgery appears even more promising. Animal models have proven critical to investigating the pathophysiology of varicocele. PMID- 26816755 TI - Clinical and investigative applications of Raman spectroscopy in Urology and Andrology. AB - Raman spectroscopy (RS) is an optical technique that allows for real-time interrogation of biologic tissues with chemical specificity. Using a diode laser, incident photons are scattered on the tissue of interest and the spectral wavelength output is a reflection of the tissues' molecular fingerprint. Naturally, this technology has come into clinical usage to evaluate benign versus malignant tissue. Within the field of Urology, RS has seen tremendous growth as an optical biopsy tool for the real-time evaluation of diseases of the bladder, prostate, kidney, and testis. With such growing fervor for this emerging spectroscopic modality, we present a current summary of clinical studies utilizing RS within Urology and Andrology to highlight its potential applications. PMID- 26816756 TI - Microsurgical denervation of the rat spermatic cord and its connection to the diagnosis and treatment of chronic orchialgia: a bench to bedside experience. AB - Chronic orchialgia is a common urologic problem, however, determination of the etiology is often difficult and the pathophysiology is poorly understood. As a result, there is no clear algorithm for surgical treatment for men who have failed conservative medical treatment. This review aims to describe microsurgical denervation of the rat spermatic cord (SC) and summarize several surgical techniques that have been described in the literature ranging from orchiectomy to epididymectomy to vasectomy reversal for post-vasectomy orchialgia. More recent studies advocate for microsurgical denervation of the spermatic cord (MDSC), which can be performed with a standard operating microscope or laparoscopic/robotic techniques providing optical magnification. Data regarding efficacy and complications for all surgical treatments is outlined. Experimental modalities, such as the use of multiphoton microscopy (MPM) to identify and ablate nerves surrounding the vas deferens are also described. Finally, given the fact that chronic orchialgia often affects young men, we summarize safety data generated from an animal model regarding the effect of microsurgical denervation on the structure and function of the testis and vas deferens. PMID- 26816754 TI - Surgical management of male infertility: an update. AB - Male factor infertility is common, affecting 7% of the total population and up to half of couples who are trying to conceive. Various surgical and reconstructive options allow biological paternity depending on the etiology of the male factor issues. This article describes historical treatments and newer approaches, discussing the role for traditional open surgery, microsurgery and robotic surgery, as well as interventional radiologic procedures in the management of male infertility. PMID- 26816757 TI - Updates on sperm retrieval techniques. AB - In the most extreme form of male infertility, the male partner is azoospermic. The advent of in vitro fertilization (IVF)-intracytoplasmic sperm injection (ICSI) has revolutionized our ability to treat azoospermia in both obstructive and non-obstructive cases. In obstructive azoospermia, it allows paternity without microsurgical reproductive tract reconstruction and also in cases where the reproductive tract is unreconstructable. In men with non-obstructive azoospermia, microdissection testicular sperm extraction (mTESE) has allowed us to retrieve sperm in men with exceedingly low sperm production. The introduction of microsurgery in sperm retrieval improves sperm yields and quality while minimizing the chance of surgical morbidity. PMID- 26816758 TI - Robotic microsurgery in male infertility and urology-taking robotics to the next level. AB - The initial reports of robotic assisted microsurgery began to appear in the early 1990s. Animal and early human studies were the initial publications. Larger series papers have recently been published from a few institutions. The field of robotic assisted microsurgery is still in evolution and so are adjunctive tools and instruments. It is clearly a different and unique skill set-is it microsurgery or is it robotic surgery, or both. It is clear from history that the art of surgery evolves over time to encompass new technology as long as the outcomes are better for the patient. Our current robotic platforms may not be ideal for microsurgery, however, the use of adjunctive tools and instrument refinement will further its future potential. This review article presents the current state of the art in various robotic assisted microsurgical procedures in male infertility and urology. Some novel applications of taking microsurgery to areas not classically accessible (intra-abdominal vasovasostomy) and adjunctive tools will also be presented. PMID- 26816759 TI - Clinical trials using the Shang Ring device for male circumcision in Africa: a review. AB - Male circumcision (MC) reduces the risk of HIV and other sexually transmitted infections (STIs), including human papillomavirus (HPV) and herpes simplex virus type 2 (HSV-2), and is recommended as an important component of a comprehensive package of HIV prevention interventions. While computer modeling has demonstrated that substantial reductions in HIV could be achieved with rapid scale-up of MC services in sub-Saharan Africa, scale-up has lagged due to scarcity of trained providers coupled with relative technical difficulty of recommended surgical MC techniques. Simplified techniques, such as devices, have the potential to allow for a more rapid roll-out of MC. One such device is the Shang Ring, a novel disposable MC device that eliminates the need for suturing and has been on the Chinese market since 2005. Results from Chinese studies have demonstrated that the Shang Ring is both safe and easy to use. Since 2008, a series of studies using the Shang Ring for adult MC have been carried out in Kenya, Uganda and Zambia, according to guidelines established by World Health Organization (WHO) for clinical evaluation of new devices for adult MC. These include a proof of concept study, a study of delayed removal of the Shang Ring, two studies comparing Shang Ring circumcision to conventional surgical approaches, and a large field trial to evaluate safety of Shang Ring circumcision during routine service delivery. Results from these studies demonstrate that the Shang Ring has an excellent safety profile and that Shang Ring circumcision is relatively easy to teach and learn, making Shang Ring MC an appealing technique for use in sub Saharan Africa where doctors are in short supply and non-physician providers such as nurses and clinical officers are playing a major role in providing MC through task shifting. Shang Ring MC and device removals were uneventfully performed by trained nurses and clinical officers, who preferred the Shang Ring to conventional surgical techniques. Adverse event rates were similar to those observed with conventional surgical circumcision and were managed with, at most, minor interventions, resolving with no long-term sequale. Perhaps one of the biggest advantages of the Shang Ring is the relatively short 3-6 minutes procedure time. Importantly, men also preferred the Shang Ring compared to conventional circumcision and satisfaction with cosmetic appearance of their circumcised penis was very high. The vast majority of participants in studies in Africa as well as China have reported few problems and little disruption to daily life while wearing the device. The Shang Ring holds great promise as an innovative technology that has the potential to facilitate the safe and effective scale-up of circumcision services in settings where MC is not widely used and where the burden of HIV-disease is high. PMID- 26816760 TI - Application of Raman spectroscopy in Andrology: non-invasive analysis of tissue and single cell. AB - As a fast, label-free and non-invasive detection method, Raman spectroscopy has been widely used for the interrogation of biological tissues, any alterations of molecular structure and chemical components during pathological processes would be identified and revealed via the differences on Raman spectrum. In clinics, the Raman spectroscopy has great potentials to provide real-time scanning of living tissues and fast diagnosis of diseases, just like discrimination of various carcinomas. A portable Raman spectroscopy which combined Raman system with an optical fiber probe has also been developed and proved to be able to provide intraoperative assistance in both human study and animal models. In Andrology, interests in Raman spectroscopy had just emerged. In this review, we summarized the progress about the utility of Raman spectroscopy in Andrology, the literatures were gathered from PubMed and Ovid database using MeSH terms associated with prostate, testis, seminal plasma and single sperm cell. We also highlighted the serious challenges as to the final clinical application of Raman technique. In conclusion, research in Raman spectroscopy may herald a new era for Andrology. PMID- 26816761 TI - Male infertility microsurgical training. AB - A strong foundation in microsurgical techniques is imperative for urologists and clinical andrologists specializing in male infertility. Laboratory-based microsurgical training enhances surgical skills, improves surgeon confidence, and reduces stress and operating time, thereby benefiting both the patient and the surgeon. The laboratory environment additionally allows for the development of novel and innovative techniques. This review provides guidelines for setting up a microsurgical laboratory to develop and enhance microsurgical skills using synthetic and animal models. PMID- 26816762 TI - The epidemiology of renal trauma. AB - INTRODUCTION: Nonoperative and minimally invasive management techniques for both blunt and penetrating renal trauma have become standard of care over the past decades. We sought to examine the modern epidemiology of renal trauma over the past decade. METHODS: A systematic review of PubMed from the past decade was conducted to examine adult and pediatric renal trauma. A total of 605 articles were identified. Of these, 15 adult and 5 pediatric articles met our a priori search criteria. RESULTS: There is a lack of uniform reporting of the renal trauma demographics precluding accurate assessment. Despite this, we were able to elucidate the following details. Renal trauma predominately affects young adult males, and the etiology is predominantly blunt. Among blunt injuries, motor vehicle crashes are most common among adult and pediatric patients. Nonoperative care was utilized in 94.8% of reviewed manuscripts with a 5.4% nephrectomy rate. DISCUSSION: There do not appear to be any startling changes in the presentation of adult and pediatric renal trauma over the past decade. Nonoperative care continues to be utilized as primary therapy. Increased attention on the reporting of renal trauma demographics is necessary to improve detection of trends. CONCLUSIONS: Increased reporting of the presenting demographics of adult and pediatric renal trauma is encouraged to assist future assessment of epidemiology. PMID- 26816763 TI - Presentation, management, and outcomes of complications following prostate cancer therapy. AB - OBJECTIVE: To characterize complications of prostate cancer therapy and operative management in patients referred to our institution for surgical intervention. MATERIALS AND METHODS: Data was abstracted from a retrospectively collected single surgeon database at a large tertiary care referral-based medical center. Variables included age, prostate cancer therapy, complication(s) and their management, and number of operations. Descriptive statistics were used. RESULTS: From 2006-2010, 890 patients underwent genitourinary surgery, of which 139 were to treat complications arising from prostate cancer therapy. Complications stemmed from radical prostatectomy (RP) monotherapy, RP and external beam radiation therapy (EBRT) or brachytherapy (BT), EBRT only, BT only, and combination EBRT and BT. Complications included urinary incontinence (UI), urethral strictures, bladder neck contractures, and fistulas. UI and bladder neck contractures were more common in patients treated with RP or RP with EBRT or BT. Strictures and fistulas were common in patients treated with EBRT or BT. Interventions included direct vision internal urethrotomy, artificial urinary sphincter, urethral reconstruction, UroLume urethral stent, urethral sling, repair of fistulas, and balloon dilation. Forty eight percent of patients required multiple operations. The median number of interventions was two. CONCLUSIONS: We operatively managed patients treated with non-surgical and surgical modalities for prostate cancer. Complications included UI, fistulas, strictures, and bladder neck contractures. These were managed with a variety of operative interventions. As more men undergo treatment for localized disease, more will inevitably have complications stemming from interventions. PMID- 26816764 TI - Overall satisfaction, sexual function, and the durability of neophallus dimensions following staged female to male genital gender confirming surgery: the Institute of Urology, London U.K. experience. AB - BACKGROUND AND PURPOSE: What factors influence transgender men's decisions to undergo (and to not undergo) specific genital gender confirming surgeries (GCS) has not been described in the literature. Sexual function outcomes related to clitoral transposition and penile prosthesis placement is also not well described. Durability of neophallus dimensions after phalloplasty has not been described. A better understanding of these factors is necessary for pre-op counseling. We sought to assess patient genital-GCS related satisfaction, regret, pre/post-op sexual function, genital preferences, and genital measurements post op. MATERIALS AND METHODS: We evaluated ten female to male transgender patients who had previously undergone suprapubic pedicle-flap phalloplasty [suprapubic phalloplasty (SP); N=10] and 15 who had undergone radial artery forearm-flap phalloplasty [(RAP); N=15; 5/15 without and 10/15 with cutaneous nerve to clitoral nerve anastomosis] at our center (UK). We queried patients' surgery related preferences and concerns, satisfaction, and sexual function pre/post surgery, and accounted for whether patients had undergone clitoral transposition and/or cutaneous-to-clitoral nerve anastomosis. We measured flaccid and (where applicable) erect length and girth using a smart-phone app we designed. RESULTS: Mean age at surgery and follow-up for those that underwent SP was 35.1 and 2.23 years, and 34 and 6.8 for those that underwent RAP. Mean satisfaction scores were 9.1/10 and 9/10 for those that underwent SP and RAP, respectively. No patient (0%) regretted starting genital-GCS surgery. All (100%) patients that could achieve orgasm before GCS with clitoral transposition could achieve orgasm after surgery, and the vast majority reported preserved quality of erogenous sensation by our transposition technique. All (100%) RAP and 9/10 SP patients reported masturbation with their phallus. Inflatable penile prosthesis placement was not associated with decreased erogenous sensation/orgasm. Penile dimensions were relatively stable through follow-up for both groups. Our App length measurements correlated with a ruler within +/-<4.5%. CONCLUSIONS: Female-to-male genital-GCS offered in 3-stages was associated with high overall satisfaction and no regret among our sample. Sexual function appears to be preserved after both clitoral transposition and inflatable prosthesis placement, and consolidation of erogenous sensation to the phallus was described as important to all subjects. Discussion of patient's pre-op sexual function, as well as specific concerns and preferences related to specific genital-GCS surgeries is important. PMID- 26816765 TI - Distal urethroplasty for fossa navicularis and meatal strictures. AB - Distal urethral strictures involving the fossa navicularis and meatus represent a unique subset of urethral strictures that are particularly challenging to reconstructive urologists. Management of distal urethral strictures must take into account not only maintenance of urethral patency but also glans cosmesis. A variety of therapeutic approaches exist for the management of distal urethral strictures, including dilation, meatotomy, extended meatotomy, flap urethroplasty, and substitution grafting. Common etiologies for distal urethral strictures include lichen sclerosus, instrumentation, and prior hypospadias repair. Proper patient selection is paramount to the ultimate success and durability of the treatment, which should be individualized and include an assessment of the stricture etiology, location, and burden, and patient-centered goals of care. PMID- 26816766 TI - Innovative approaches for complex penile urethral strictures. AB - Urethral strictures are a common urologic disease that arises from varied etiologies. These strictures range in severity from simple, short lesions to complex, long defects. Likewise, the management approach varies based on the complexity of the lesion. We reviewed the literature of urethral stricture disease and its management. In particular we have focused on complex strictures of the male penile urethra. Often these cases cannot be managed with traditional reconstructive techniques and require newer approaches. Furthermore tissue engineered graft materials provide a possible tissue source for future reconstructive endeavors. PMID- 26816767 TI - Management of adults with prior failed hypospadias surgery. AB - Hypospadias is one of the most prevalent anomalies of the male genitalia. Contemporary hypospadias repair is very successful, but patients that have the surgery fail often require multiple surgeries throughout their life. Complications from failed hypospadias repairs have a significant impact on patients both psychologically and physically. Failed hypospadias repair encompasses a spectrum of problems that include hypospadias recurrence with an ectopic meatus, urethral fistula, urethral stricture, and ventral penile curvature. Repairs of hypospadias complications can be challenging due to the poor quality of surrounding tissue from disruption of normal vasculature in the re-operative field associated with the underlying disorder. One of the most challenging issues is dealing with urethral strictures. There have been multiple methods described at repairs of these in both a single stage and multiple staged procedures. Particular attention has been directed towards applications of grafts due to worse outcomes with flaps. Buccal mucosa has emerged as the leading graft material in staged repairs. When counseling patients with failed hypospadias it is important to discuss the expected outcome as repairs directed towards a terminally positioned meatus with a straight phallus may require multiple surgeries due to post-operative complications as well as the necessity of proceeding in a staged approach. PMID- 26816769 TI - The role of noninvasive testing and questionnaires in urethroplasty follow-up. AB - Urethroplasty is the preferred surgical approach for the management of urethral stricture disease. To date, no standard has been established to evaluate stricture recurrence after urethral reconstruction, though both invasive and non invasive methods are used widely. In this article we review the role of noninvasive testing and questionnaires in urethral monitoring after urethroplasty. PMID- 26816770 TI - Treating the cystine stone former presents a singular clinical challenge. PMID- 26816768 TI - Bladder neck contracture. AB - Bladder neck contracture (BNC) is a well-described complication of the surgical treatment of benign and malignant prostate conditions. Nevertheless, etiologies of BNC development are highly dependent on the primary treatment modality undertaken with BNC also occurring after pelvic radiation. The treatment options for BNC can range from simple, office-based dilation procedures to more invasive, complex abdomino-perineal reconstructive surgery. Although numerous strategies have been described, a patient-specific approach is usually necessary in the management of these complex patients. In this review, we highlight various therapeutic maneuvers described for the management of BNC and further delineate a tailored approach utilized at our institution in these complicated patients. PMID- 26816772 TI - Making sense of dietary calcium and urinary stone disease. PMID- 26816771 TI - Calcium intake and urinary stone disease. AB - Calcium homeostasis is a complicated and incompletely understood process that is primarily regulated through an interaction between the intestines, kidneys, and bones. Intestinal calcium absorption is determined by many factors including the amount of regular calcium intake, as well as vitamin D and parathyroid hormone levels. Intestinal calcium absorption is likely different between stone formers and non-stone formers, with higher levels of calcium absorption in those with a history of stones independent of their calcium intake. We no longer recommend dietary calcium restriction as this may lead to bone demineralization and an increase in stone formation. Practitioners need to continue to educate patients to maintain moderate dietary calcium intake. The effect of calcium supplementation on stone formation is currently controversial. It is likely that large doses of supplemental calcium, especially if taken separate from a meal, may lead to stone formation. When necessary, stone forming patients should be encouraged to take their calcium supplements with a meal and their stone disease should be monitored. PMID- 26816773 TI - Gastric bypass surgery patients warrant special attention for preventing urinary stones. PMID- 26816774 TI - The role of Randall plaques on kidney stone formation. AB - Randall's plaque is microscopically a plaque of calcium deposited in the interstitial tissue of the renal papilla. These plaques are thought to serve as a nidus for urinary stone formation. Large amounts of Randall's plaque are unique to idiopathic calcium oxalate stone formers. Although Randall's plaques can be found in other stone formers, only in idiopathic calcium oxalate stone formers, the detailed mechanism of stone overgrow on plaque was thoroughly studied. Calcification is invariably located in the basement membrane of the loops of Henle and from there plaques spread through the interstitium toward urothelium. Within the basement membrane, mineral deposits are individual laminated particles in which zones of crystal and organic matrix overlay each other. In the interstitium, the particles appear to fuse on the collagen bundles to form a syncytium of crystal islands in an organic sea. By loss of integrity of urothelium, regions of plaque are exposed to urine. The exposed surface will touch and be covered by molecules of urine origin, including osteopontin, Tamm Horsfall protein, and crystals formed under urine supersaturations, resulting in a ribbon of alternating matrix and crystal. Eventually crystallization escapes from matrix modulation and crystals extend outward into the space of urine and begin to form a calcium oxalate stone proper. Randall's plaque plays an important role and is prerequisite of kidney stone formation in idiopathic calcium oxalate stone formers. PMID- 26816775 TI - Alexander Randall may have had it right after all. PMID- 26816776 TI - Reactive oxygen species may unite many mechanisms by which calcium oxalate stones form. PMID- 26816777 TI - Economic impact of urinary stones. AB - Kidney stones have been rising in prevalence in the United States and worldwide, and represent a significant cost burden. Cost effectiveness research in this area may enable improvements in treatment efficiency that can benefit patients, providers and the healthcare system. There has been limited research in the cost effectiveness of surgical interventions for stone disease, despite the diverse treatment approaches that are available. Medical expulsive therapy (MET) has been shown to improve rates of stone passage for ureteral stones, and there is evidence that this practice should be liberalized from the standpoint of both clinical and cost effectiveness. While conservative treatment following a primary stone event appears to be cost effective, the economic impact of medical therapy for recurrent stone formers requires clarification despite its clinical efficacy. Future study regarding the cost effectiveness of prevention and interventions for stone disease are likely to improve both the quality and efficiency of care. PMID- 26816778 TI - The days of cost effective management for nephrolithiasis are already upon us. PMID- 26816780 TI - The link between metabolic syndrome and nephrolithiasis: a white whale for understanding urinary stone disease. PMID- 26816779 TI - Metabolic syndrome and nephrolithiasis. AB - PROBLEM: This review focuses on the association between the metabolic syndrome (MS) and nephrolithiasis. FINDINGS: Associations between nephrolithiasis and systemic diseases are recognized, including atherosclerosis, cardiovascular (CV) disease, hypertension (HNT), diabetes mellitus (DM)-composite risk factors grouped as the MS. Kidney stones incidence is increasing in this particularly high risk group. Those with stones are prone to the disease and those with the systemic disease are at risk for stone formation, with the highest incidence in persons with multiple traits of the MS. Pathophysiologic explanations for the increased stone risk related to MS are likely complex and dynamic. CONCLUSIONS: Kidney stones disproportionately affect persons with some or all traits of MS. One unifying theory may be of a common systemic malfunction of inflammation and tissue damage as an underlying mechanism, but it is unlikely to be the only mechanistic explanation. Further research is needed to investigate this and other hypotheses that go beyond population based and urine physiochemical studies in order to elucidate the mechanisms behind the individual disease states themselves. PMID- 26816781 TI - Perioperative cultures and the role of antibiotics during stone surgery. AB - Urinary tract infection and urosepsis are the most common complications associated with the procedures urologists employ to manage stone disease. Recommendations regarding antibiotic prophylaxis and utilization of perioperative urine and stone culture prior to shockwave lithotripsy (SWL) or endoscopic intervention have evolved overtime. We sought to provide readers with a comprehensive consensus regarding these most recent recommendations. PMID- 26816782 TI - Looking beyond the guidelines for perioperative antibiotics in nephrolithiasis. PMID- 26816784 TI - Moderation may be the best fad diet for urinary stone disease. PMID- 26816783 TI - Fad diets and their effect on urinary stone formation. AB - The influence of unhealthy dietary habits on urinary stone formation has been widely recognized in literature. Dietary advice is indeed the cornerstone prescription for prevention of nephrolithiasis as well. However, only a small amount of medical literature has addressed the influence of popular or fad diets, often self-prescribed for the management of obesity and overweight or for cultural beliefs, on the risk of kidney stones. Thereby in this paper we analyze the current knowledge on the effects of some popular diets on overall lithogenic risk. High-protein diets, like Dukan diet, raise some concerns, since animal proteins are able to increase urinary calcium and to decrease urinary citrate excretion, thus leading to a high overall lithogenic risk. Low-carbohydrate diets, like Atkins diet or zone diet, may have a protective role against kidney stone formation, but there are also evidences stating that this dietary approach may rise calciuria and decrease citraturia, since it is generally associated to a relatively high intake of animal proteins. Vegan diet can be harmful for urinary stone disease, especially for the risk of hyperuricemia and micronutrient deficiencies, even if only few studies have addressed this specific matter. On the other side, the benefits of a lacto-ovo-vegetarian diet on kidney stone prevention have been largely emphasized, provided that the intake of calcium and oxalate is balanced. Traditional Mediterranean diet should exert a protective effect on nephrolithiasis as well, even if specific studies have not been carried out yet. High phytate and antioxidant content of this diet have however demonstrated to be beneficial in preventing the formation of new or recurrent calculi. Anyway, at the current state of knowledge, the most effective dietary approach to prevent kidney stone disease is a mild animal protein restriction, a balanced intake of carbohydrates and fats and a high intake of fruit and vegetables. Other fundamental aspects, which are often neglected in fad diets, are a normal intake of milk and dairy products and salt restriction. All these nutritional aspects should be greatly taken into account when patients who are willing to undergo fad or commercial diets ask for dietary advice. PMID- 26816785 TI - Advances in ureteral stents. AB - Ureteral stents are commonly used in urology. Every urologist is familiar with the problems that are associated with stents including infection, encrustation, and bothersome symptoms. These problems limit and affect the use of ureteral stents which are necessary, even in light of the problems they can cause. New designs such as a helically cut ureteral stent which is designed to stretch and conform to the ureter is designed to improve comfort. Drug-eluting designs with an antimicrobial (triclosan) are designed to reduce bacterial adherence to ureteral stents. Chlorhexidine, an antiseptic, has been incorporated into a stent and held in place by a slow release varnish to prevent biofilm formation. Combinations of antibiotics coated directly on the stent and administered systemically have been shown to reduce stent colonization both in vitro and in vivo. Gel-based ureteral stents were also showed to reduce bacterial infection and colonization. Bioabsorbable materials have also been designed to reduce infection, symptoms and prevent the forgotten stent syndrome. Newer designs including stents based on guidewire technology, gels, and a combination of self expanding wire stents with polymer films are reviewed. There is hope on the horizon that new stents will be able to effectively tackle problems that are often seen with ureteral stents. PMID- 26816786 TI - Advances in ureteroscopy. AB - Ureteroscopy (URS) is a procedure which has been constantly evolving since the development of first generation devices 40 years ago. Progress towards smaller and more sophisticated equipment has been particularly rapid in the last decade. We review the significant steps that have been made toward improving outcomes and limiting morbidity with this procedure which is central to the management of urolithiasis and other upper urinary tract pathology. PMID- 26816787 TI - Balancing the utility of new technology against cost in urinary stone disease. PMID- 26816788 TI - Pediatric urology focused issue. PMID- 26816789 TI - Do endocrine disruptors cause hypospadias? AB - INTRODUCTION: Endocrine disruptors or environmental agents, disrupt the endocrine system, leading to various adverse effects in humans and animals. Although the phenomenon has been noted historically in the cases of diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT), the term "endocrine disruptor" is relatively new. Endocrine disruptors can have a variety of hormonal activities such as estrogenicity or anti-androgenicity. The focus of this review concerns on the induction of hypospadias by exogenous estrogenic endocrine disruptors. This has been a particular clinical concern secondary to reported increased incidence of hypospadias. Herein, the recent literature is reviewed as to whether endocrine disruptors cause hypospadias. METHODS: A literature search was performed for studies involving both humans and animals. Studies within the past 5 years were reviewed and categorized into basic science, clinical science, epidemiologic, or review studies. RESULTS: Forty-three scientific articles were identified. Relevant sentinel articles were also reviewed. Additional pertinent studies were extracted from the reference of the articles that obtained from initial search results. Each article was reviewed and results presented. Overall, there were no studies which definitely stated that endocrine disruptors caused hypospadias. However, there were multiple studies which implicated endocrine disruptors as one component of a multifactorial model for hypospadias. CONCLUSIONS: Endocrine disruption may be one of the many critical steps in aberrant development that manifests as hypospadias. PMID- 26816790 TI - The role of pre-operative androgen stimulation in hypospadias surgery. AB - The hormonal stimulation for the purpose of penile enlargement before the hypospadias repair has been commonly used, but rarely reported. In addition to functional outcome, dihydrotestosterone (DHT) pretreatment has been suggested to improve cosmetic outcome in a preliminary randomized study. Since the randomized and controlled clinical trials on this topic are insufficient, the hormonal agent, the route of administration, dosing schedule, and the timing of treatment has been remained controversial. In order to confirm the efficiency of hormonal treatment, further well designed randomized studies with a larger number of patients and a placebo group are warranted. PMID- 26816791 TI - Unnecessary diagnostic imaging: a review of the literature on preoperative imaging for boys with undescended testes. AB - Cryptorchidism or undescended testis is one of the most common pediatric disorders of the male endocrine glands and the most common genital disorder identified at birth. Ultrasound is commonly ordered for boys with undescended testes prior to referral to a surgical specialist, but its sensitivity and specificity is insufficient to reliably localize non-palpable testes and thus confers unnecessary costs to the patient and the healthcare system. We review the ability of ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) to reliably locate undescended testes and emphasize whether diagnostic imaging should change the decision to operate or the surgical approach for boys with cryptorchidism. PMID- 26816792 TI - What lessons can be learned from testicular histology in undescended testes? AB - Over the last 40-50 years studies involving thousands of testicular biopsies in boys with cryptorchidism have contributed to our knowledge of testicular histopathology and our understanding of the effects of cryptorchidism on the normal development of the germinal epithelium. Growth and maturation of germ cells and Leydig cells are crucial to allow boys to reach normal fertility potential. The following aberrations in testicular development are seen in cryptorchid testes: a decrease in total germ cell numbers, failure of fetal gonocytes (stem cells) to transform into adult dark (Ad) spermatogonia, failure for Ad spermatogonia to mature into primary spermatocytes, Leydig cell hypoplasia, and testicular fibrosis. All of these findings have been found to have a strong negative correlation with a boy's age at the time of orchidopexy. Some of these findings have prognostic significance in regards to fertility potential especially when coupled with key clinical findings such as hormonal findings, age at orchidopexy, testicle size, laterality and location of cryptorchid testes. This review focuses on key lessons learned from testicular histology in cryptorchid testes. PMID- 26816793 TI - Does early orchidopexy improve fertility? AB - Cryptorchidism or undescended testis (UDT) is a common problem in the pediatric male population. While spontaneous testicular descent occurs in the majority of cases, orchidopexy is the definitive treatment in those with remaining cryptorchid testis. A long established sequela to cryptorchidism is reduced fertility in the adult male and recent guidelines have advocated for earlier orchidopexy as studies have shown improvement in fertility rates when surgery is performed before one year of age. Further studies continue to validate these recommendations as recent research demonstrates crucial developmental steps even in very young boys. These steps are critical to complete testicular maturation and a loss of these milestones has increasingly been shown to decrease fertility later in life. This review examines the histological findings, hormonal data, and paternity rates from those who have undergone orchidopexy at varying ages and summarizes current recommendations aimed at preserving fertility as much as possible in this population. PMID- 26816795 TI - The clinical utility of testicular prosthesis placement in children with genital and testicular disorders. AB - Testicular prosthesis placement is a useful important adjunctive reconstructive therapy for managing children with testicular loss or absence. Though these prostheses are functionless, experience has shown that they are extremely helpful in creating a more normal male body image and in preventing/relieving psychological stress in males with a missing testicle. With attention to details of implant technique, excellent cosmetic results can be anticipated in simulating a normal appearing scrotum. PMID- 26816794 TI - Fertility preservation for boys and adolescents facing sterilizing medical therapy. AB - Improvements in childhood cancer survival have allowed boys and their families to increasingly focus on quality of life after therapy, particularly their future ability to father children. Treatments should maintain comprehensive cancer care goals and consider the long-term quality of life of these children. While semen cryopreservation is a well-established method of fertility preservation for post pubertal children, the use of cryopreserved pre-treatment testicular tissue represents a promising, yet experimental method of fertility preservation for prepubertal males facing sterilizing therapy. Healthcare providers should counsel families about the fertility risks of therapy, discuss or refer patients for standard fertility preservation options, and consider experimental approaches to fertility preservation while being mindful of the ethical questions these treatments raise. PMID- 26816796 TI - Adolescent varicocele: limited indications for treatment during puberty and adolescence. AB - A varicocele is defined as an abnormal dilatation of the pampiniform plexus of veins of the testis. The vast majority of children and adolescents with varicoceles have no subjective symptoms. The complete work-up of patient diagnosed with a varicocele involves a physical exam in supine and prone position with and without Valsalva, and the use of ultrasound to measure testicular volume and blood flow. Because of growth issues occurring during puberty and adolescence, serial follow-ups may be done to determine any detrimental change in testicular size and symptomatology. The main difference of an adolescent varicocele is the fact that semen parameters are unavailable and do not count for treatment strategy. In this review, the focus is made on a recent study that has evaluated the ultimate endpoint: paternity. It appears that screening and treatment of a varicocele in the adolescent period does not influence the ultimate chance of paternity. PMID- 26816797 TI - My indications for treatment of the adolescent varicocele (and why?). AB - What to do with the adolescent varicocele? With merging the information obtained from an extensive review of the literature with our own clinical research, I believe that we already have knowledge enough to say that the adolescent with a varicocele often is in the midst of a progressive disease process. Strong evidence already exists that well more than the majority of Tanner 5 boys with a varicocele and 20% asymmetry will already have abnormally low total motile sperm counts (TMCs) and likely abnormally low sperm concentration as well. There are now many studies in addition to common sense to support the value of % asymmetry as a marker of future abnormal sperm parameters. While we know that some boys at lower Tanner stages who present with asymmetry will have catch-up growth during adolescence, we also know that almost all boys with 15% asymmetry or greater in conjunction with a Doppler detected peak retrograde flow (PRF) of 38 cm/s or greater will end up with greater than 20% asymmetry on follow-up. There also are some boys of concern with less asymmetry but instead have small testes bilaterally, perhaps as a result of the left varicocele slowing the growth of the right testicle and/or an associated undetected or overlooked palpable right varicocele that is also negatively affecting the right testicle. Fortunately, we now have another marker available, i.e., total testicular volume (TTV), to assist in decision making for the adolescent falling into this scenario. Once markers are in place in an early Tanner stage boy with a varicocele that indicate that abnormal semen parameters will likely be present when a Tanner 5 stage of development is reached, there is no reason to wait until the child is older so that a semen analysis can be comfortably requested for the documentation. One argument in favor of waiting is that abnormal semen parameters in a Tanner 5 male usually are reversible. However, how do we know that once abnormal parameters are reversed they then will stay normal in a testicle that already has incurred damage. In other words, I feel it is best to operate once the indicators are in place. We do not want to be suddenly surprised when that individual when older has difficulty fathering a child at a time in life when surgery might be too late to resolve what has taken years to develop. Within this manuscript I will try to document my reasons for the aforementioned rationale. PMID- 26816799 TI - Pros, cons, and ethics of HPV vaccine in teens-Why such controversy? AB - INTRODUCTION: Human papillomavirus (HPV) infection remains one of the most commonly sexually transmitted infections in both females and males. HPV viruses are associated with several manifestations including genital warts, but more importantly for urology practitioners, cervical and penile carcinomas and recurrent genital condylomata in both sexes. The incidence of HPV-related carcinomas has increased in cervical, oropharyngeal, vulvar, penile, and anal cancers. Effective vaccines have been available for almost a decade, but widespread adoption of vaccine administration has been problematic for multiple reasons. Many countries (over 100) have adopted vaccine programs for females and an increasing number of countries are extending the indications to include males between the ages of 9-26. There still seems to be controversy surrounding these universal vaccination programs as well as some ethical and practical concerns regarding the administration of a vaccine for diseases that are associated with sexual contact in both sexes, especially during the early adolescent years. OBJECTIVE: The objective was to provide a review of the available literature so pediatric and adult urologists may be more aware of the issues related to HPV vaccination in order to more effectively counsel patients and parents regarding the risks, benefits, and public health issues regarding HPV vaccination. This topic is especially relevant to pediatric urologists who see patients in the target age group for the HPV vaccine. There has been an explosion of literature regarding HPV vaccination programs and the relative difficulty in adopting the vaccine series with a completion rate of under 50% of patients in the recommended age ranges for vaccination. METHODS: Articles were obtained from an extensive Medline literature search (1998-present) to evaluate the current HPV vaccination regimens for teenagers with special emphasis on the urologically focused disease burden. RESULTS: The adoption of universal HPV vaccination has been difficult, but appears to be increasing over time as public education improves and governmentally- mandated vaccine programs increase. Despite the ethical concerns raised, the benefits of vaccination with regard to cancer prevention outweigh the risks and potential side effects related to the quadrivalent vaccine administration. Clearly, more follow-up over time is required to document these improvements in public health. Urologists need to remain aware of the prevention strategies for HPV infection and should help with counseling parents and patients in the appropriate age groups for HPV vaccination. Urology providers need to help engage and educate the parents and teenage patients to help promote broader adoption of the HPV vaccine regimen. PMID- 26816800 TI - Report of 6(th) Great Wall Translational Andrology and Urology Forum & 7(th) Asian-Pacific Society of Men's Health and Anti-aging Meeting (GTAUF2014 & APSMHA2014). PMID- 26816801 TI - TAU is endorsed by the Genitourinary Medical Association of China International Exchange and Promotive Association for Medical and Health Care (GUA-CPAM): new door open for academic collaboration. PMID- 26816798 TI - The role of laparoscopy in children with groin problems. AB - The use of laparoscopic surgery has grown dramatically in recent years in most all types of surgery. Historically, the early use of laparoscopic surgery was for pelvic and groin problems. In this article we review the current technique, indications, benefits and complications of laparoscopy in diagnosis and management of various groin problems in children including undescended testes (non-palpable and palpable) and inguinal hernia. PMID- 26816802 TI - Focused issue on contemporary management of urethral stricture. PMID- 26816803 TI - Imaging of urethral stricture disease. AB - Accurate imaging of urethral strictures is critical for preoperative staging and planning of reconstruction. The current gold standard, retrograde urethrography (RUG), allows for accurate diagnosis, staging, and delineation of urethral strictures, and remains a cornerstone in the management of urethral stricture disease. In complex situations, the RUG can be combined with voiding cystourethrogram (VCUG) in order to better visualize the posterior urethra or complex distraction defects. Direct visualization of the stricture by cystoscopy, either retrograde or antegrade, can provide additional information as to the location and appearance of stricture, as well as precise location on fluoroscopic imaging. Sonourethrography (SU) is a useful adjunct to allow for three dimensional assessment of stricture length and location, and can be a useful intraoperative assessment tool, however, its use remains limited to a second-line setting. Cross-sectional imaging in the form of computed tomography (CT) or magnetic resonance urethrography can provide additional three-dimensional information of anatomic structures and their relations, and can serve as a useful adjunct in complex clinical scenarios. PMID- 26816804 TI - Dorsal inlay buccal mucosal graft (Asopa) urethroplasty for anterior urethral stricture. AB - Asopa described the inlay of a graft into Snodgrass's longitudinal urethral plate incision using a ventral sagittal urethrotomy approach in 2001. He claimed that this technique was easier to perform and led to less tissue ischemia due to no need for mobilization of the urethra. This approach has subsequently been popularized among reconstructive urologists as the dorsal inlay urethroplasty or Asopa technique. Depending on the location of the stricture, either a subcoronal circumferential incision is made for penile strictures, or a midline perineal incision is made for bulbar strictures. Other approaches for penile urethral strictures include the non-circumferential penile incisional approach and a penoscrotal approach. We generally prefer the circumferential degloving approach for penile urethral strictures. The penis is de-gloved and the urethra is split ventrally to exposure the stricture. It is then deepened to include the full thickness of the dorsal urethra. The dorsal surface is made raw and grafts are fixed on the urethral surface. Quilting sutures are placed to further anchor the graft. A Foley catheter is placed and the urethra is retubularized in two layers with special attention to the staggering of suture lines. The skin incision is then closed in layers. We have found that it is best to perform an Asopa urethroplasty when the urethral plate is >=1 cm in width. The key to when to use the dorsal inlay technique all depends on the width of the urethral plate once the urethrotomy is performed, stricture etiology, and stricture location (penile vs. bulb). PMID- 26816805 TI - The contemporary management of urethral strictures in men resulting from lichen sclerosus. AB - Lichen sclerosus (LS) is a chronic, inflammatory disease primarily involving the genital skin and urethra in males. Historically, the treatment of this common condition was a challenge due to its uncertain etiology, variable response to therapy, and predilection to recur. The etiology of LS is still debated and has been linked to autoimmune disease, infection, trauma, and genetics. Today, topical steroids are a mainstay of therapy for patients, even in the presence of advanced disease, and can induce regression of the disease. In advanced cases, surgery may be required and range from circumcision, meatoplasty, or, in the case of advanced stricture disease, urethroplasty or perineal urethrostomy. When urethroplasty is required, the use of genital skin as a graft or flap is to be avoided due to the predilection for recurrence. Surgical management should be approached only after failure of more conservative measures due to the high risk of recurrence of LS in the repaired site despite the use of buccal grafting. LS may be associated with the development of squamous cell carcinoma and for this reason, patients should undergo biopsy when LS is suspected and long-term surveillance is recommended. PMID- 26816806 TI - Staged urethroplasty in the management of complex anterior urethral stricture disease. AB - Staged buccal mucosa graft urethroplasty has emerged as a reliable procedure for difficult anterior urethral strictures not amenable to one-stage graft or flap reconstruction. It has primarily been used for strictures and/or fistulae occurring after previous surgery for hypospadias or those related to lichen sclerosus (LS). Success rates in these patient populations have improved when compared to earlier techniques. However, prior studies have demonstrated a number of patients requiring more than two procedures to complete the reconstruction, as well as some who have been content with their voiding pattern after the first operation and therefore elected to forego second stage tubularization. In this setting, we have reviewed the surgical technique and summarized previously published work. There may be an opportunity to complete more of these repairs in two operations using additional oral mucosa at the time of tubularization. PMID- 26816807 TI - Augmented urethroplasty with pseudospongioplasty in the treatment of penile strictures. AB - Strictures involving the penile urethra generally require tissue transfer techniques. Ventral graft placement usually is avoided in the penile urethra because of the relative paucity of viable corpus spongiosal tissue necessary for vascularization and support. Instead, grafts are commonly placed dorsally using either an onlay or inlay technique. However, the successful use of ventrally placed grafts in the penile urethra supported by a pseudospongioplasty has recently been reported. The incorporation of a pseudospongioplasty provides a well-vascularized milieu for successful graft take in the penile urethra. This technique incorporates periurethral flaps of tunica dartos and Buck's fascia for graft coverage. Pseudospongioplasty in the penile urethra has been shown to have a similar efficacy to standard spongioplasty in the bulbar urethra. Additionally, pseudospongioplasty outcomes are comparable to other graft augmentation techniques performed in the penile urethra. In penile strictures, where there is a paucity of spongiosal tissue, pseudospongioplasty for coverage of a ventral graft is a reliable option. PMID- 26816808 TI - Non-transecting bulbar urethroplasty. AB - Excision and end-to-end anastomosis (EPA) has been the preferred urethroplasty technique for short bulbar strictures and is associated with an excellent functional outcome. Driven by concerns over the potential morbidity associated with dividing the urethra, therefore compromising spongiosal blood flow, as well as spongiofibrosis being superficial in the majority of non-traumatic bulbar strictures, the non-transecting technique for bulbar urethroplasty has been developed with the aim of achieving the same success as EPA without the morbidity associated with transection. This manuscript highlights the fundamental principles underlying the ongoing debate-transection or non-transection of the strictured bulbar urethra? The potential advantages of avoiding dividing the corpus spongiosum of the urethra are discussed. The non-transecting anastomotic procedure together with its various modifications are decribed in detail. Our experience with this technique is presented. Non-transecting excision of spongiofibrosis with preservation of well vascularised underlying spongiosum provides an excellent alternative to dividing the urethra during urethroplasty for short non-traumatic proximal bulbar strictures. PMID- 26816809 TI - 7-flap perineal urethrostomy. AB - Perineal urethrostomy (PU) has been performed with success for the treatment of refractory and advanced urethral stricture disease for at least the past six decades. Here, we review the indications and outcomes of PU for indications such as complex hypospadias repair and urethral stricture disease resulting from trauma, infection, and failure of prior urethroplasty. We also describe the role of 7-flap PU, a novel alternative to the conventional approach that offers the surgeon added flexibility in tailoring urethrostomy creation based on intraoperative findings. The authors' updated experience with 7-flap PU demonstrates a comparable 95% success rate in patients with a wide variety of stricture etiology. PU through either a conventional approach or a 7-flap technique is a valuable option for improving the quality of life in patients with debilitating urethral stricture disease. PMID- 26816810 TI - In situ urethroplasty after artificial urinary sphincter cuff erosion. AB - Artificial urinary sphincter (AUS) cuff erosion is a challenging complication traditionally managed with device removal and Foley catheter drainage. Urethral stricture can result secondary to the healing process, delaying AUS reimplantation. In situ urethroplasty (ISU) technique is a definitive repair at the time of device removal. Early results demonstrate a decreased rate of stricture formation compared to traditional management with little additional operative time and no additional complications. Patients undergoing ISU have less delay prior to AUS reimplantation, leading to possible benefit in health-related quality of life (HRQL) outcomes. PMID- 26816811 TI - Management of the devastated posterior urethra and bladder neck: refractory incontinence and stenosis. AB - Stricture of the proximal urethra following treatment for prostate cancer occurs in an estimated 1-8% of patients. Following prostatectomy, urethral reconstruction is feasible in many patients. However, in those patients with prior radiation therapy (RT), failed reconstruction, refractory incontinence or multiple comorbidities, reconstruction may not be feasible. The purpose of this article is to review the evaluation and management options for patients who are not candidates for reconstruction of the posterior urethra and require urinary diversion. Patient evaluation should result in the decision whether reconstruction is feasible. In our experience, risk factors for failed reconstruction include prior radiation and multiple failed endoscopic treatments. Pre-operative cystoscopy is an essential part of the evaluations to identify tissue necrosis, dystrophic calcification, or tumor in the urethra, prostate and/or bladder. If urethral reconstruction is not feasible it is imperative to discuss options for urine diversion with the patient. Treatment options include simple catheter diversion, urethral ligation, and both bladder preserving and non preserving diversion. Surgical management should address both the bladder and the bladder outlet. This can be accomplished from a perineal, abdominal or abdomino perineal approach. The devastated bladder outlet is a challenging problem to treat. Typically, patients undergo multiple procedures in an attempt to restore urethral continuity and continence. For the small subset who fails reconstruction, urinary diversion provides a definitive, "end-stage" treatment resulting in improved quality of life. PMID- 26816812 TI - Management of radiation-induced urethral strictures. AB - Radiation as a treatment option for prostate cancer has been chosen by many patients. One of the side effects encountered are radiation-induced urethral strictures which occur in up to 11% of patients. Radiation damage has often left the irradiated field fibrotic and with poor vascularization which make these strictures a challenging entity to treat. The mainstay of urologic management remains an urethroplasty procedure for which several approaches exist with variable optimal indication. Excision and primary anastomoses are ideal for shorter bulbar strictures that comprise the majority of radiation-induced urethral strictures. One advantage of this technique is that it does not require tissue transfers and success rates of 70-95% have consistently been reported. Substitution urethroplasty using remote graft tissue such as buccal mucosa are indicated if the length of the stricture precludes a tension-free primary anastomosis. Despite the challenge of graft survival in radiation-damaged and poorly vascularized recipient tissue, up to 83% of patients have been treated successfully although the numbers described in the literature are small. The most extensive repairs involve the use of tissue flaps, for example gracilis muscle, which may be required if the involved periurethral tissue is unable to provide sufficient vascular support for a post-operative urethral healing process. In summary, radiation-induced urethral strictures are a challenging entity. Most strictures are amenable to excision and primary anastomosis (EPA) with encouraging success rates but substitution urethroplasty may be indicated when extensive repair is needed. PMID- 26816813 TI - Pro: endoscopic realignment for pelvic fracture urethral injuries. AB - Patients with pelvic fracture urethral distraction injuries may benefit from early endoscopic realignment. Realignment is associated with a low risk of immediate complications and has a high success rate for achieving catheter placement. Review of over thirty studies assessing for subsequent urethral stenosis, including at least a dozen that directly compare realignment to suprapubic diversion along, conclude that there is a benefit averaging at least 35% in favor of realignment. Furthermore, realignment may result in easier subsequent urethroplasty and possibly shorter stenoses. PMID- 26816814 TI - Con: bulbomembranous anastomotic urethroplasty for pelvic fracture urethral injuries. AB - Current literature remains controversial regarding whether to treat patients sustaining pelvic fracture urethral injuries (PFUIs) with primary endoscopic realignment (PER) versus suprapubic tube (SPT) placement alone with elective bulbomembranous anastomotic urethroplasty (BMAU). Success rates for PER following PFUI are wide-ranging, depending on various authors' definitions of what defines a successful outcome. At our institution, for SPT/BMAU patients, the mean time to definitive resolution of stenosis was dramatically shorter compared to PER cases. The vast majority of PER patients required multiple endoscopic urethral interventions and/or experienced various other adverse events which were rarely noted among the SPT/BMAU group. While PER does occasionally result in urethral patency without the need for further intervention, the risk of delay in definitive treatment and potential for adverse events has led to a preference for SPT and elective BMAU at our institution. PMID- 26816815 TI - Is there a sexual life after treatment of cancer? PMID- 26816816 TI - How to evaluate sexual health in cancer patients: development of the EORTC sexual health questionnaire for cancer patients. AB - BACKGROUND: The aim of the study is to describe the development of a comprehensive European Organisation for Research and Treatment of Cancer (EORTC) questionnaire to assess sexual health of female and male cancer patients and for cancer survivors. METHODS: According to the EORTC guidelines, the development of an EORTC sexual health questionnaire is typically organised in four phases. The first phases comprise a literature search following interviews with patient and health care professionals (HCPs) (phase 1) and the operationalization into items (phase 2). The translation process is formally conducted according to the EORTC QLG Translation guidelines with a rigorous forward-backward procedure supported by native speakers. RESULTS: Studies on sexuality in oncology patients which were identified by a literature search predominantly focused on issues of activity, experiences of sexual dysfunction, and satisfaction with sexual functioning. The literature review identified themes beyond these aspects. In total 53 potentially relevant issues were presented to 107 patients and 83 HCPs, different evaluations were found. CONCLUSIONS: A questionnaire that includes physical, psychological, and social aspects of sexuality of cancer survivors will be needed. Pre-testing and validation of the questionnaire will be done in future (phases 3 and 4). Divergent ratings of patients and professionals should be further investigated. PMID- 26816817 TI - Surgery and hormonal treatment for prostate cancer and sexual function. AB - Prostate cancer (PC) is one of the most common cancers effecting men today. With earlier detection and improvements in available treatment modalities, there still remains significant morbidity associated with the treatment of PC. Male sexual health and erectile function are greatly impacted by these therapies and remain a concern to PC survivors. This article reviews the current literature on male sexual health following radical prostatectomy (RP) or androgen ablation therapy for PC. Each treatment modality affects male sexual function to an appreciable level, although certain patients have better outcomes if they have preoperative potency, are younger, or have nerve-sparing surgery. There is a delayed recovery up to 2 years seen in erectile function following RP. With androgen deprivation therapy (ADT), attempts can be made at different administration strategies and exercise may possibly play a role in maintaining erectile function. Penile rehabilitation protocols attempt to protect erectile function immediately following therapy through different modalities, although no one approach has been agreed upon. PMID- 26816819 TI - Co-constructing sexual recovery after prostate cancer: a qualitative study with couples. AB - BACKGROUND: Men are likely to experience deterioration in sexual functioning as a consequence of treatment for prostate cancer. Indeed, sexual difficulties are common across all treatment modalities. OBJECTIVE: To determine the impact of treatment for prostate cancer on intimacy and sexual expression/relationships from the perspective of couples. METHODS: An observational study was conducted including in-depth interviews with 18 people affected by prostate cancer; comprising eight couples and two individual men. RESULTS: Four categories were identified that illustrated the impact of prostate cancer on intimacy and sexual recovery. These related to social influences and language used to describe the loss or recovery of sexual activities; difficulties in discussing sexual activity with clinicians; the clash of individual impact of prostate cancer recovery versus the impact on the couple, and the re-integration of sexual activities into the relationship. CONCLUSIONS: Though only one person in a partnership experiences cancer, these data indicated the extent to which prostate cancer treatment also impacts on partners. The study indicates that adjustment to erectile dysfunction (ED) takes time, but is a highly significant event in couples' lives and its importance should not be under-estimated. Consequently, we suggest that relational models of care should be considered, whereby side-effects are recognised as impacting on both members of the partnership (for example ED, or lack or ejaculate). Supportive care in this context, therefore, may best be based on a relational approach using language and interventions that are appropriate to the patient and their situation. PMID- 26816818 TI - Penile rehabilitation after radical prostatectomy: does it work? AB - CONTEXT: Erectile dysfunction (ED) represents one of the most common long-term side effects in patients with clinically localized prostate cancer (PCa) undergoing nerve-sparing radical prostatectomy (RP). OBJECTIVE: To analyze the role of penile rehabilitation in the recovery of erectile function (EF) after nerve-sparing RP. EVIDENCE SYNTHESIS: Penile rehabilitation is defined as the use of any intervention or combination with the goal not only to achieve erections sufficient for satisfactory sexual intercourses, but also to return EF to preoperative levels. The concept of rehabilitation is based on the implementation of protocols aimed at improving oxygenation, preserving endothelial structure, and preventing smooth muscle structural alterations. Nowadays, the most commonly adopted approaches for penile rehabilitation after nerve-sparing RP are represented by the administration of phosphodiesterase type-5 inhibitors (PDE5 Is), intracorporeal injection therapy, vacuum erection devices (VED), and the combination of these therapies. Several basic science studies support the rational for the adoption of penile rehabilitation protocols. Particularly, rehabilitation, set as early as possible, seems to be better than leaving the erectile tissues unassisted. On the other hand, results from solid prospective randomized trials finally assessing the long-term beneficial effects of PDE5-Is, intracavernosal injections, or VED on EF recovery after surgery are still lacking. CONCLUSIONS: Although preclinical evidences support the rationale for penile rehabilitation after nerve-sparing RP, clinical studies reported conflicting results regarding its efficacy on long-term EF recovery. Nowadays, which is the optimal rehabilitation program still represents a matter of debate. PMID- 26816820 TI - Challenges to treat hypogonadism in prostate cancer patients: implications for endocrinologists, urologists and radiotherapists. AB - The literature suggests that the serum testosterone level required for maximum androgen receptor (AR) binding may be in the range of nanomolar and above this range of concentrations; this sexual hormone may not significantly affect tumour biology. This assumption is supported by clinical studies showing that cell proliferation markers did not change when serum T levels increased after exogenous T treatment in comparison to subjects treated with placebo. However, a considerable part of the global scientific community remains sceptical regarding the use of testosterone replacement therapy (TRT) in men suffering from hypogonadism and prostate cancer (Pca). The negative attitudes with respect to testosterone supplementation in men with hypogonadism and Pca may be justified by the relatively low number of clinical and preclinical studies that specifically dealt with how androgens affect Pca biology. More controversial still is the use of TRT in men in active surveillance or at intermediate or high risk of recurrence and treated by curative radiotherapy. In these clinical scenarios, clinicians should be aware that safety data regarding TRT are scanty limiting our ability to draw definitive conclusions on this important topic. In this review we critically discuss the newest scientific evidence concerning the new challenges in the treatment of men with hypogonadal condition and Pca providing new insights in the pharmacological and psychological approaches. PMID- 26816822 TI - Breast cancer and sexual function. AB - As the most common malignancy affecting women within the United States, breast cancer can bring about multiple physical and psychological challenges. Among the greatest challenges are those associated with female sexual function. Chemotherapy, endocrine therapy, surgeries and radiation can all have a large effect in altering a woman's sexual health and function. Sexual concerns result in significant emotional distress, including sadness/depression, issues related to personal appearance, stigma, and negative impacts on personal relationships. In this article, we discuss some of the specific challenges that present with each type of treatment and the socio-physical impact they have on survivorship. Among the most detrimental to sexual function, are the use of chemotherapy and endocrine therapy. Additionally, anatomical changes that transpire in patients who have undergone surgery or radiation therapy (RT), disrupt perceptions of body image. Here we will discuss and also review the contemporary literature to determine effective management and treatment of sexual dysfunction. PMID- 26816821 TI - Pharmacologic and surgical therapies for sexual dysfunction in male cancer survivors. AB - The recent recognition that many men experience sexual dysfunction following their diagnosis and treatment of genitourinary cancers, has led to the development multiple varied strategies that attempt to restore or preserve that function. In this manuscript we review the understanding of why it happens, highlight novel management strategies and discuss the concept of penile rehabilitation (PR) following prostate cancer (PCa) treatment, glans preserving strategies among men diagnosed with penile cancer and address the controversial issue of testosterone therapy in men with PCa. PMID- 26816824 TI - Pelvic radiotherapy and sexual function in women. AB - BACKGROUND: During the past decade there has been considerable progress in developing new radiation methods for cancer treatment. Pelvic radiotherapy constitutes the primary or (neo) adjuvant treatment of many pelvic cancers e.g., locally advanced cervical and rectal cancer. There is an increasing focus on late effects and an increasing awareness that patient reported outcomes (PROs) i.e., patient assessment of physical, social, psychological, and sexual functioning provides the most valid information on the effects of cancer treatment. Following cure of cancer allow survivors focus on quality of life (QOL) issues; sexual functioning has proved to be one of the most important aspects of concern in long term survivors. METHODS: An updated literature search in PubMed was performed on pelvic radiotherapy and female sexual functioning/dysfunction. Studies on gynaecological, urological and gastrointestinal cancers were included. The focus was on the period from 2010 to 2014, on studies using PROs, on potential randomized controlled trials (RCTs) where female sexual dysfunction (FSD) at least constituted a secondary outcome, and on studies reporting from modern radiotherapy modalities. RESULTS: The literature search revealed a few RCTs with FSD evaluated as a PRO and being a secondary outcome measure in endometrial and in rectal cancer patients. Very limited information could be extracted regarding FSD in bladder, vulva, and anal cancer patients. The literature before and after 2010 confirms that pelvic radiotherapy, independent on modality, increases the risk significantly for FSD both compared to data from age-matched healthy control women and compared to data on patients treated by surgery only. There was only very limited data available on modern radiotherapy modalities. These are awaited during the next five years. Several newer studies confirm that health care professionals are still reluctant to discuss treatment induced sexual dysfunction with patients. CONCLUSIONS: Pelvic radiotherapy has a persistent deteriorating effect on the vaginal mucosa impacting negatively on the sexual functioning in female cancer patients. Hopefully, modern radiotherapy modalities will cause less vaginal morbidity but results are awaited to confirm this assumption. Health care professionals are encouraged to address potential sexual dysfunction both before and after radiotherapy and to focus more on quality than on quantity. PMID- 26816825 TI - Biopsychosocial predictors of sexual function and quality of sexual life: a study among patients with colorectal cancer. AB - OBJECTIVE: A low sexual function (SF) has been reported in patients with colorectal cancer. However, research often focusses on clinical predictors of SF, hereby omitting patients' subjective evaluation of SF [i.e., the quality of sexual life (QoSL)] and psychosocial predictors of SF and QoSL. In addition, research incorporating a biopsychosocial approach to SF and QoSL is scarce. Therefore, this study aimed to evaluate (I) relatedness between SF and the QoSL, (II) the course of SF and QoSL, and (III) biopsychosocial predictors of SF and QoSL. METHODS: Patients completed questionnaires assessing sociodemographic factors (i.e., age, sex) and personality characteristics (i.e., neuroticism, trait anxiety) before surgery. Questionnaires assessing psychological (i.e., anxious and depressive symptoms, body image, fatigue) and social (i.e., sexual activity, SF, non-sensuality, avoidance of sexual activity, non-communication, relationship function) aspects were measured preoperative and 3, 6, and 12 months after surgery. Clinical characteristics were obtained from the Eindhoven Cancer Registry (ECR). Bivariate correlations evaluated relatedness between SF and QoSL. Linear mixed-effects models examined biopsychosocial predictors of SF and QoSL. RESULTS: SF and QoSL are related constructs (r=0.206 to 0.642). Compared to preoperative scores, SF did not change over time (P>0.05). Overall, patients' QoSL decreased postoperatively (P=0.001). A higher age (beta=-0.02, P=0.006), fatigue (beta=-0.02, P=0.034), not being sexually active (beta=-0.081, P<0.001), and having a stoma (beta=0.37, P=0.035) contributed to a lower SF. Having rectal cancer (beta=-1.64, P=0.003), depressive symptoms (beta=-0.09, P=0.001), lower SF (beta=1.05, P<0.001), and more relationship maladjustment (beta=-0.05, P=0.027) contributed to a lower QoSL (P<0.05). In addition, partners' SF (beta=0.24, P<0.001) and QoSL (beta=0.30, P<0.001) were predictive for patients' SF and QoSL, respectively. A significant interaction between time and gender was reported for both outcomes (P's=0.002). CONCLUSIONS: SF and QoSL are related but distinctive constructs. The course of SF and QoSL differed. Different biopsychosocial predictors were found for SF and QoSL. The contribution of partner-related variables to patients' outcomes suggests interdependence between patients and partners. Men and women showed different SF and QoSL trajectories. We recommend that health care professionals, when discussing sexuality, realize that SF and QoSL are no interchangeable terms and should, therefore, be discussed as two separate entities. In addition, it is favored that clinicians focus not only on biological predictors of SF and QoSL, but obtain a broader perspective in which they also pay attention to psychosocial factors that may impair SF and QoSL. More in depth research on interdependence between patients and partners, biopsychosocial predictors of partners' SF and QoSL, and gender effects is needed. PMID- 26816823 TI - Emotional and sexual concerns in women undergoing pelvic surgery and associated treatment for gynecologic cancer. AB - The surgical management of gynecologic cancer can cause short- and long-term effects on sexuality, emotional well being, reproductive function, and overall quality of life (QoL). Fortunately, innovative approaches developed over the past several decades have improved oncologic outcomes and reduced treatment sequelae; however, these side effects of treatment are still prevalent. In this article, we provide an overview of the various standard-of-care pelvic surgeries and multimodality cancer treatments (chemotherapy and radiation therapy) by anatomic site and highlight the potential emotional and sexual consequences that can influence cancer survivorship and QoL. Potential screening tools that can be used in clinical practice to identify some of these concerns and treatment side effects and possible solutions are also provided. These screening tools include brief assessments that can be used in the clinical care setting to assist in the identification of problematic issues throughout the continuum of care. This optimizes quality of care, and ultimately, QoL in these women. Prospective clinical trials with gynecologic oncology populations should include patient reported outcomes to identify subgroups at risk for difficulties during and following treatment for early intervention. PMID- 26816827 TI - Focused issue on urological oncology. PMID- 26816826 TI - The primary health care physician and the cancer patient: tips and strategies for managing sexual health. AB - There is a large and growing population of long-term cancer survivors. Primary care physicians (PCPs) are playing an increasingly greater role in the care of these patients across the continuum of cancer survivorship. In this role, PCPs are faced with the responsibility of managing a range of medical and psychosocial late effects of cancer treatment. In particular, the sexual side effects of treatment which are common and have significant impact on quality of life for the cancer survivor, often go unaddressed. This is an area of clinical care and research that has received increasing attention, highlighted by the presentation of this special issue on Cancer and Sexual Health. The aims of this review are 3 fold. First, we seek to overview common presentations of sexual dysfunction related to major cancer diagnoses in order to give the PCP a sense of the medical issues that the survivor may present with. Barriers to communication about sexual health issues between patient/PCPs in order are also described in order to emphasize the importance of PCPs initiating this important conversation. Next, we provide strategies and resources to help guide the PCP in the management of sexual dysfunction in cancer survivors. Finally, we discuss case examples of survivorship sexual health issues and highlight the role that a PCP can play in each of these case examples. PMID- 26816828 TI - Bacille-Calmette-Guerin non-responders: how to manage. AB - Intravesical immunotherapy with bacille-Calmette-Guerin (BCG) is indicated in the treatment of high-risk and intermediate-risk non-muscle invasive bladder cancer (NMIBC). Our goal is to describe the various disease states following induction and maintenance BCG and to describe contemporary treatment options and the current and projected clinical trial landscape for patients who recur following BCG therapy. PMID- 26816829 TI - Upper urinary tract disease: what we know today and unmet needs. AB - PURPOSE: Upper tract urothelial carcinoma (UTUC) is a rare and poorly investigated disease. Intense collaborative efforts have increased our knowledge and improved the management of the disease. The objective of this review was to discuss recent advances and unmet needs in UTUC. METHODS: A non-systematic Medline/PubMed literature search was performed on UTUC using the terms "upper tract urothelial carcinoma" with different combinations of keywords. Original articles, reviews and editorials in English language were selected based on their clinical relevance. RESULTS: UTUC is a disease with specific epidemiologic and risk factors different to urothelial carcinoma of the bladder (UCB). Similarly to UCB, smoking increases the risk of UTUC and worsens its prognosis, whereas aristolochic acid (AA) exposure and mismatch repair genes abnormality are UTUC specific risk factors. A growing understanding of biological pathways involved in the tumorigenesis of UTUC has led to the identification of promising prognostic/predictive biomarkers. Risk stratification of UTUC is difficult due to limitations in staging and grading. Modern imaging and endoscopy have improved clinical decision-making, and allowed kidney-sparing management and surveillance in favorable-risk tumors. In high-risk tumors, radical nephroureterectomy (RNU) remains the standard. Complete removal of the intramural ureter is necessary with inferiority of endoscopic management. Post-RNU intravesical instillation has been shown to decrease bladder cancer recurrence rates. While the role of neoadjuvant cisplatin based combination chemotherapy and lymphadenectomy are not clearly established, the body of evidence suggests a survival benefit to these. There is currently no evidence for adjuvant chemotherapy (AC) in UTUC. CONCLUSIONS: Despite growing interest and understanding of UTUC, its management remains challenging, requiring further high quality multicenter collaborations. Accurate risk estimation is necessary to avoid unnecessary RNUs while advances in technology are still required for optimal kidney-sparing approaches. PMID- 26816830 TI - Risk based neoadjuvant chemotherapy in muscle invasive bladder cancer. AB - Muscle invasive bladder cancer (MIBC) is an aggressive disease that frequently requires radical cystectomy (RC) to achieve durable cure rates. Surgery is most effective when performed in organ-confined disease, with the best outcomes for those patients with a pT0 result. The goals of neoadjuvant chemotherapy (NC) are to optimize surgical outcomes for a malignancy with limited adjuvant therapies and a lack of effective salvage treatments. Despite level 1 evidence demonstrating a survival benefit, the utilization of NC has been hampered by several issues, including, the inability to predict responders and the perception that NC may delay curative surgery. In this article, we review the current efforts to identify patients that are most likely to derive a benefit from NC, in order to create a risk-adapted paradigm that reserves NC for those who need it. PMID- 26816831 TI - Indications for biopsy and the current status of focal therapy for renal tumours. AB - The increased detection of small renal masses (SRMs) has focused attention on their uncertain natural history. The development of treatment alternatives and the discovery of biologically targeted drugs have also raised interest. Renal mass biopsies (RMBs) have a crucial role as they provide the pathological, molecular and genetic information needed to classify these lesions and guide clinical management. The improved accuracy has improved our knowledge of the behaviour of different tumour histologies and opened the potential for risk adapted individualized treatment approaches. To date, studies have demonstrated that percutaneous ablation is an effective therapy with acceptable outcomes and low risk in the appropriate clinical setting. Although partial nephrectomy (PN) is still considered the standard treatment for SRM, percutaneous ablation is increasingly being performed and if long-term efficacy is sustained, it may have a wider application for SRMs after biopsy characterization. PMID- 26816832 TI - Sequence of treatment in locally advanced and metastatic renal cell carcinoma. AB - The spectrum of drugs that have shown activity in advanced or metastatic renal cell carcinoma (RCC) has led to a debate on the optimal sequence of treatments. There is agreement on recommending targeted agents as the standard of care in this disease. Uncertainty, however, remains on the best first-line drug choice. Physicians and patients may select sunitinib, bevacizumab in combination with interferon-alpha (IFN-alpha), pazopanib, or-in poor risk patients-temsirolimus. There are also a variety of therapies with proven efficacy on hand in the second line setting: sorafenib, pazopanib, axitinib, and everolimus. While most randomized RCC trials assessed progression free survival (PFS) as primary endpoint, some agents were shown to improve median overall survival (OS), and given in sequence they have extended the life expectancy of RCC patients from 13 months in the cytokine era to over 30 months. Despite the progress made, there are sobering aspects to the oncologic success story in RCC, as the new treatments do not obtain an objective response or disease stabilization (SD) in all patients. There are also as yet no predictors to select patients who might benefit and those who are primary resistant to specific drugs, and ultimately almost all patients will experience disease progression. Bearing inevitable treatment failure in mind, availability of further drugs and switching therapy while the patient is in a condition to continue pharmacotherapy is essential. Of note, depending on the setting, only 33-59% of patients receive second-line treatment. In this review we present data on first-, second-, and third-line treatment in RCC, and discuss the difficulties in their interpretation in the context of treatment sequence. We summarize biological aspects and discuss mechanisms of resistance to anti-angiogenic therapy and their implications for treatment selection. PMID- 26816834 TI - Active surveillance and focal therapy for low-intermediate risk prostate cancer. AB - Low risk and many cases of low-intermediate risk prostate cancer, are indolent, have little or no metastatic potential, and are not life threatening. Major advances have been made in understanding who these patients are, and in encouraging the use of conservative management in such individuals. Conservative management incorporates the early identification of those 'low risk' patients who harbor higher risk disease, and benefit from definitive therapy. Based on the current algorithm of PSA followed by systematic biopsy, this represents about 30% of newly diagnosed low risk patients. A further small proportion of patients with low risk disease demonstrate biological progression to higher grade disease. Men with lower risk disease can defer treatment, usually for life. Men with higher risk disease that can be localized to a relatively small volume of the prostate may be candidates for focal, prostate sparing therapy. The results of active surveillance, embodying conservative management with selective delayed intervention for the subset who are re-classified as higher risk over time based on repeat biopsy, imaging, or biomarker results, have shown that this approach is safe in the intermediate to long term, with a 1-5% cancer specific mortality at 15 years. Further refinement of the surveillance approach is ongoing, incorporating MRI, targeted biopsies, and molecular biomarkers. PMID- 26816833 TI - The current and future role of magnetic resonance imaging in prostate cancer detection and management. AB - PURPOSE: Accurate detection of clinically significant prostate cancer (PC) and correct risk attribution are essential to individually counsel men with PC. Multiparametric MRI (mpMRI) facilitates correct localization of index lesions within the prostate and MRI-targeted prostate biopsy (TPB) helps to avoid the shortcomings of conventional biopsy such as false-negative results or underdiagnosis of aggressive PC. In this review we summarize the different sequences of mpMRI, characterize the possibilities of incorporating MRI in the biopsy workflow and outline the performance of targeted and systematic cores in significant cancer detection. Furthermore, we outline the potential of MRI in patients undergoing active surveillance (AS) and in the pre-operative setting. MATERIALS AND METHODS: An electronic MEDLINE/PubMed search up to February 2015 was performed. English language articles were reviewed for inclusion ability and data were extracted, analyzed and summarized. RESULTS: Targeted biopsies significantly outperform conventional systematic biopsies in the detection of significant PC and are not inferior when compared to transperineal saturation biopsies. MpMRI can detect index lesions in app. 90% of cases as compared to prostatectomy specimen. The diagnostic performance of biparametric MRI (T2w + DWI) is not inferior to mpMRI, offering options to diminish cost- and time consumption. Since app 10% of significant lesions are still MRI-invisible, systematic cores seem to be necessary. In-bore biopsy and MRI/TRUS-fusion-guided biopsy tend to be superior techniques compared to cognitive fusion. In AS, mpMRI avoids underdetection of significant PC and confirms low-risk disease accurately. In higher-risk disease, pre-surgical MRI can change the clinically-based surgical plan in up to a third of cases. CONCLUSIONS: mpMRI and targeted biopsies are able to detect significant PC accurately and mitigate insignificant PC detection. As long as the negative predictive value (NPV) is still imperfect, systematic cores should not be omitted for optimal staging of disease. The potential to correctly classify aggressiveness of disease in AS patients and to guide and plan prostatectomy is evolving. PMID- 26816835 TI - Hormonal therapy and chemotherapy in hormone-naive and castration resistant prostate cancer. AB - The management of advanced castration resistant prostate cancer (CRPC) has been rapidly changing and is still evolving. In the last years, there has been an increasing knowledge of prostate cancer biology. New therapeutic agents and approaches have been evaluated demonstrating benefits in survival and quality of life in patients with metastatic prostate cancer. PMID- 26816836 TI - Advances in the treatment of testicular cancer. AB - Germ cell tumors (GCT) are relatively uncommon, accounting for only 1% of male malignancies in the United States. It has become an important oncological disease for several reasons. It is the most common malignancy in young men 15-35 years old. GCTs are among a unique numbers of neoplasms where biochemical markers play a critical role. Finally, it is a model of curable cancer. In this review we discuss cancer epidemiology, genetics, and therapeutic principles. Recent advances in the management of stage I GCT and controversies in the management of post chemotherapy residual mass are presented. PMID- 26816837 TI - D-004 ameliorates phenylephrine-induced urodynamic changes and increased prostate and bladder oxidative stress in rats. AB - BACKGROUND: Lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) mainly depend on alpha1-adrenoreceptors (alpha1-ADR) stimulation, but a link with oxidative stress (OS) is also involved. D-004, a lipid extract of Roystonea regia fruits, antagonizes ADR-induced responses and produces antioxidant effects. The objective of this study was to investigate whether D-004 produce antioxidant effects in rats with phenylephrine (PHE) induced urodynamic changes. METHODS: Rats were randomized into eight groups (ten rats/group): a negative vehicle control and seven groups injected with PHE: a positive control, three treated with D-004 (200, 400 and 800 mg/kg) and three others with tamsulosin (0.4 mg/kg), grape seed extract (GSE) (250 mg/kg) and vitamin E (VE) (250 mg/kg), respectively. RESULTS: Effects on urinary total volume (UTV), volume voided per micturition (VM), malondialdehyde (MDA) and carbonyl groups (CG) concentrations in prostate and bladder homogenates were study outcomes. While VM and UTV lowered significantly in the positive control as compared to the negative control group, the opposite occurred with prostate and bladder MDA and CG values. D-004 (200-800 mg/kg) increased significantly both VM and UTV, lowered significantly MDA in prostate and bladder homogenates, and reduced GC levels only in the prostate. Tamsulosin increased significantly VM and UTV, but unchanged oxidative variables. GSE and VE unchanged the UTV, whereas VE, not GSE, modestly but significantly attenuated the PHE-induced decrease of VM. CONCLUSIONS: Single oral administration of D-004 (200-800 mg/kg) was the only treatment that ameliorated the urodynamic changes and reduced increased oxidative variables in the prostate of rats with PHE-induced prostate hyperplasia. PMID- 26816838 TI - Novel pilot films providing indispensable information in pharmaco cavernosography. AB - BACKGROUND: Conventional pharmaco-cavernosography provides little information on penile venous anatomy, although it is indispensible in documenting veno-occlusive erectile dysfunction (ED). We propose an innovative method, which may provide additional insight into the penile venous structure. METHODS: From July 2010 to November 2012, 96 impotent men, aged 20 to 75 years, underwent this method of pharmaco-cavernosography in which two sets of 60 mL of 50% omnipaque solution administered intracavernously by themselves. The first set of pilot cavernosograms was taken at intervals of five, ten, twenty and thirty seconds after the commencement of the injection. The second set of cavernosograms was taken in the same intervals within 30 minutes following the pilot set, preceded by the injection of 20 ug prostaglandin E1 (PGE1). Analysis was conducted on the drainage veins including deep dorsal vein (DDV), cavernosal veins (CVs) and para arterial veins (PAVs) accordingly. The veins demonstrated in the pilot cavernosograms, and the second set, were compared in terms of venous numbers and presentation percentage. RESULTS: There was a statistically significant difference (P<0.001) between the total number of independent venous drainage channels and the presentation percentage of DDV, CVs and PAVs observed in the pilot cavernosograms, and those in second set (4.5 vs. 2.1; 97.47%, 60.33%, and 38.91% vs. 57.06%, 29.34%, and 19.08%, respectively). CONCLUSIONS: Compared with conventional pharmaco-cavernosography methods, pilot cavernosograms are readily able to show detailed penile venous anatomy. It is therefore may be concluded that pilot cavernosograms is a valuable addition to conventional protocols of pharmaco-cavernosography. PMID- 26816839 TI - Does tunica anatomy matter in penile implant? AB - BACKGROUND: Overall prosthesis survival is important in penile implant, which remains the final viable solution to many patients with refractory erectile dysfunction (ED). This paper is to retrospectively study the role of the anatomy of tunica albuginea (TA). METHODS: From March 1987 to March 1991 while the TA was regarded as a circumferential single layer, 21 organically ED men, aged from 27 to 77, received penile prosthesis implantation and were allocated to conventional group. From August 1992 to March 2013 while the tip of Hegar's dilator was categorically directed medial-dorsally during corporal dilatation derived from newfound TA as a bi-layered structure with a 360 degrees complete inner circular layer and a 300 degrees incomplete outer longitudinal coat, 196 ED males, aged from 35 to 83, underwent penile implant and were categorized to advanced group. The model of prosthesis was recorded. Prosthesis loss rate and survival time were analyzed and the follow up period ranged from 22.4-26.4 (average 24.3) years and 0.4-20.6 (average 15.8) years to the conventional and advanced group respectively. RESULTS: To the conventional and advanced group, the number of inflatable and rigid type prosthesis used were 2, 19 and 15, 181 respectively, whereas the prosthesis loss was encountered in 50.0% (1/2), 15.8% (3/19) and 0.0% (0/15), 0.6% (1/181) respectively. And the prosthesis survival time were 5.1-6.3 (5.7) years, 1.3-26.4 (15.2) years and 6.1-16.2 (11.2) years, 0.4-20.6 (15.3) years to the conventional and advanced group respectively. Statistical significance was noted on prosthesis loss in groups (P=0.01) while the Mentor Acuform stood out in prosthesis survival. CONCLUSIONS: Anatomy-based managing maneuver appears to deliver better surgery success in penile implant. Tunica anatomy is significant in performing implant surgery. PMID- 26816840 TI - Psychosexual care in prostate cancer survivorship: a systematic review. AB - BACKGROUND: Prostate cancer (PC) is the most common cancer in men. Due to improvements in medical care, the number of PC survivors is increasing. Current literature demonstrates survivors have significant unmet needs including psychosexual care. We assess patients psychosexual needs by systematic review of literature over the past 20 years up to May 2015 in order to see what issues need to be addressed within psychosexual care. METHODS: A systematic review was conducted on PC survivorship and psychosexual care. The search strategy aimed to identify all references related to PC survivorship programme components (parts of survivorship programmes) AND survivorship AND psychosexual concerns. Search terms used were as follows: (PC OR prostate neoplasms) AND (survivorship OR survivor*) OR [psychosexual impairment or sexual dysfunction or erectile dysfunction (ED)] AND [comorbidity or quality of life (QoL)]. RESULTS: The systematic review identified 17 papers, examining unmet needs in psychosexual care post PC therapy. CONCLUSIONS: These findings of this review may change psychosexual care of PC survivors, as national and international guidance is needed. PMID- 26816841 TI - Prevention and management of post prostatectomy erectile dysfunction. AB - Sexual dysfunction is common in patients with prostate cancer (PC) following radical prostatectomy (RP). Review the available literature concerning prevention and management strategies for post-RP erectile function (EF) impairment in terms of preoperative patient characteristics, intra and postoperative factors that may influence EF recovery, and postoperative treatments for erectile dysfunction (ED). A literature search was performed using Google and PubMed database for English-language original and review articles, either published or e-published up to July 2013. The literature still demonstrates a great inconsistency in the definition of what is considered normal EF both before and after RP. Thus, using validated psychometric instruments with recognized cut-offs for normalcy and severity during the pre- and post-operative evaluation should be routinely considered. Therefore, a comprehensive discussion with the patient about the true prevalence of postoperative ED, the concept of spontaneous or pharmacologically assisted erections, and the difference between "back to baseline" EF and "erections adequate enough to have successful intercourse" clearly emerge as key issues in the eventual understanding of post-RP ED prevention and promotion of satisfactory EF recovery. Patient factors (including age, baseline EF, comorbid conditions status), cancer selection (non- vs. uni- vs. bilateral nerve-sparing), type of surgery (i.e., intra vs. inter vs. extrafascial surgeries), surgical techniques (i.e., open, laparoscopic and robotically-assisted RP), and surgeon factors (i.e., surgical volume and surgical skill) represent the key significant contributors to EF recovery. A number of preclinical and clinical data show that rehabilitation and treatment in due time are undoubtedly better than leaving the erectile tissue to its unassisted postoperative fate. The role of postoperative ED treatment for those patients who received a non-nerve-sparing RP was also extensively discussed. Optimal outcomes are achieved mainly by the careful choice of the correct patient for the correct type of surgery. Despite a plethora of potential rehabilitative approaches, they should be only considered as "strategies", since incontrovertible evidence of their effectiveness for improving natural EF recovery is limited. Conversely, numerous effective therapeutic options are available for treating post-RP ED. PMID- 26816843 TI - Inflammation in prostate cancer progression and therapeutic targeting. AB - Chronic inflammation contributes to the onset and progression of human cancer, via modifications in the tumor microenvironment by remodeling the extracellular matrix (ECM) and initiating epithelial mesenchymal transition (EMT). At the biological level, chronically inflamed cells release cytokines that are functionally dictating a constitutively active stroma, promoting tumor growth and metastasis. In prostate cancer, inflammation correlates with increased development of "risk factor" lesions or proliferative inflammatory atrophy (PIA). Chronic inflammation in benign prostate biopsy specimens can be associated with high-grade prostate tumors in adjacent areas. In this article, we discuss the current understanding of the incidence of inflammation in prostate cancer progression and the significance of the process in therapeutic targeting of specific inflammatory signaling pathways and critical effectors during tumor progression. Further understanding of the process of chronic inflammation in prostate tumor progression to metastasis will enable development and optimization of novel therapeutic modalities for the treatment of high-risk patients with advanced disease. PMID- 26816845 TI - Diagnosis and treatment of benign prostate hyperplasia in Asia. PMID- 26816844 TI - Clinicopathological features of primary angiosarcoma of the kidney: a review of 62 cases. AB - Angiosarcoma (AS) is a malignant tumor occurring in less than 2% of soft tissue sarcomas. Primary involvement of the kidney is rare, its pathogenesis remains largely unknown and it has overlapping features with other tumors of the kidney. The objective of this paper is to review the case reports of primary AS of the kidney in the literature. The search terms were primary AS of the kidney, primary renal AS and primary renal hemangiosarcoma. The total cohort of the cases reviewed was 62. The mean age of presentation was 61 years old with a predilection for the male sex. Metastatic disease at the time of diagnosis accounted for 44.9% (22/49) of the cases reported and 44.4% (12/27) of patients with non-metastatic disease at diagnosis, subsequently developed metastasis. Primary AS of the kidney is a rare malignant tumor with a poor prognosis. Local recurrence and distant metastasis is common. Primary AS of the kidney shares similar clinical presentation with other renal tumors and imaging does not allow for tumor specific diagnosis. Histopathological examination and immunohistochemistry is very important for the confirmation of the diagnosis. Current treatment options include a variable combination of surgery, radiotherapy and chemotherapy. PMID- 26816846 TI - Interstitial cystitis/bladder pain syndrome (IC/BPS) 2015: Part 1. PMID- 26816842 TI - Prostate cancer metastasis: roles of recruitment and reprogramming, cell signal network and three-dimensional growth characteristics. AB - Prostate cancer (PCa) metastasizes to bone and soft tissues, greatly decreasing quality of life, causing bone pain, skeletal complications, and mortality in PCa patients. While new treatment strategies are being developed, the molecular and cellular basis of PCa metastasis and the "cross-talk" between cancer cells and their microenvironment and crucial cell signaling pathways need to be successfully dissected for intervention. In this review, we introduce a new concept of the mechanism of PCa metastasis, the recruitment and reprogramming of bystander and dormant cells (DCs) by a population of metastasis-initiating cells (MICs). We provide evidence that recruited and reprogrammed DCs gain MICs phenotypes and can subsequently metastasize to bone and soft tissues. We show that MICs can also recruit and reprogram circulating tumor cells (CTCs) and this could contribute to cancer cell evolution and the acquisition of therapeutic resistance. We summarize relevant molecular signaling pathways, including androgen receptors (ARs) and their variants and growth factors (GFs) and cytokines that could contribute to the predilection of PCa for homing to bone and soft tissues. To understand the etiology and the biology of PCa and the effectiveness of therapeutic targeting, we briefly summarize the animal and cell models that have been employed. We also report our experience in the use of three dimensional (3-D) culture and co-culture models to understand cell signaling networks and the use of these attractive tools to conduct drug screening exercises against already-identified molecular targets. Further research into PCa growth and metastasis will improve our ability to target cancer metastasis more effectively and provide better rationales for personalized oncology. PMID- 26816847 TI - A survey on clinical practice of interstitial cystitis in Japan. AB - BACKGROUND: To explore the real-life practice of clinical management of interstitial cystitis (IC) in Japan. METHODS: A questionnaire on the number of IC patients, cystoscopic findings, diagnostic methods, and the treatment modalities was sent via e-mail to 114 medical institutions belonging to the Society of Interstitial Cystitis of Japan (SICJ). RESULTS: Completed questionnaires were returned from 62 institutions (20 university hospitals, 26 general hospitals and 16 clinics), with a response rate of 54%. The median of patient number per institution was 20 and the national number of IC patients was counted as 4,531 in Japan. The number of new patients in 2013 was 7 (median) per institution and calculated as 1,214 in total. The case volume per institution distributed broadly and skewed to a lower volume. The patients were categorized according to cystoscopic findings as either Hunner type IC with Hunner lesions (n=2,066, 45%), non-Hunner type IC with glomerulations on hydrodistension (n=1,720, 38%) or hypersensitive bladder without endoscopic abnormalities (n=304, 7%), excluding unknown (n=441, 10%). The proportion of Hunner type IC was highly variable among the institutions, ranging from 0% to 100% with a median of 29%. As for evaluation, symptom and quality of life (QOL) assessment by questionnaires, frequency volume chart, urinalysis, urine cytology, urine culture, post-void residual measurement, uroflowmetry, ultrasound and cystoscopy were widely adapted. Administration of oral medicines and intravesical instillation therapy were undertaken at 98% and 63% of institutions, respectively. Hydrodistension was commonly performed, totaling in 812 procedures at 53 institutions, while only five cystectomies were reported from four institutions. CONCLUSIONS: The survey estimated about 4,500 IC patients and 2,000 Hunner type IC patients in Japan. It also revealed a wide range of case volume, acceptable adherence to clinical guidelines, and high variability in the proportion of Hunner type IC. The variable proportions of Hunner type IC despite a high performing rate of endoscopy suggest inconsistency in diagnostic criteria for the Hunner lesion. PMID- 26816848 TI - The Interstitial Cystitis Association of America: lessons learned over the past 30 years. AB - In 1984, interstitial cystitis (IC) was considered a rare psychosomatic disorder in post-menopausal women. In 2014, the Interstitial Cystitis Association of America (ICA) celebrated its 30(th) anniversary. We've come a long way since 1984 and great progress has been made. IC is now recognized as a condition that afflicts both men and women of all ages, including children and teenagers. It is not a psychiatric disorder. Though it was once thought to be an orphan disease (defined as affecting less than 200,000 people), we now know that there are millions of women and men who suffer from IC/BPS (bladder pain syndrome). In looking back over this period, there were seven key reasons why the ICA became so successful: an extremely dedicated ICA staff, Board of Directors and volunteers; a very strong Medical Advisory Board and participation of many other urologists from across the country and around the world; cooperation of the media; epidemiological studies; the ICA's Pilot Research Program; our representation in Congress; and a strong working partnership with the National Institutes of Health (NIH). Our history may prove useful to other advocacy groups. PMID- 26816849 TI - Patient-centred standardization in interstitial cystitis/bladder pain syndrome-a PLEA. AB - Standardization has an impact on all links in the healthcare chain and directly affects patients with regard to diagnosis, treatment, eligibility for reimbursement, social benefits and care. Furthermore, patients are also affected if research goes down inappropriate pathways due to inaccurate terminology and definitions. Complex healthcare coding and electronic medical record systems and global reliance on the internet and search machines mean that new terminology or changes now need in some way to be designed to last or to be updated in a way that will cause least disruption, while still allowing for evolution, since changes have far more ramifications today than they ever did in the past. Official recognition of a condition is vital, so coding must be correct and uniform across all authorities. Potential problems must be anticipated at an early stage in the process. In order to achieve global consensus, stakeholders from all parts of the world need to communicate and collaborate with all viewpoints taken into consideration. Patients and their advocacy groups should be involved in standardization processes to ensure that all aspects of a condition are covered, that no patients or symptoms are excluded and that there is no adverse impact on the patient in practical terms following implementation. The trend today is for patients to be more involved in healthcare and decision making. We must ensure that standardisation and guidelines do not get left behind in this process of development either now or in the future. However, it is necessary to find some way of training patient representatives to enable them to participate fully in standardization and guidelines and also to encourage them to do so. PMID- 26816850 TI - Interstitial cystitis/painful bladder syndrome: the influence of modern diagnostic criteria on epidemiology and on Internet search activity by the public. AB - Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic debilitating condition that is characterised by suprapubic pain and urinary symptoms such as urgency, nocturia and urinary frequency. The prevalence of the condition is increasing due to more inclusive diagnostic criteria. Herein, we review the evolving epidemiology of IC/PBS and investigate health seeking behaviour for the condition through Internet search activity. Study selection was performed in accordance with PRISMA. In addition, global search trends for the terms 'Interstitial Cystitis' and 'Painful Bladder Syndrome' from 2005 to 2015 were also evaluated using the 'Google Trends' search application. The mean search activity per month was recorded and mean activity at annual intervals calculated. Regional search activity by country and city was also measured. Prevalence rates for IC/PBS vary according to diagnostic criteria and range from 2% to 17.3% among the general population. Increased prevalence is associated with female gender and females with one first-degree relative affected. There has been an increase in global mean search activity for IC/PBS on an annual basis since 2005. The greatest increase in search activity was in USA, Canada, United Kingdom, Australia, Ireland and India respectively. The top five cities for search activity for IC/PBS were in the USA. As diagnostic criteria for IC/PBS continues to become more inclusive it is likely that the prevalence will continue to increase. This is particularly true for the USA and Canada as these regions have demonstrated the greatest increase in Internet search activity for IC/ PBS. PMID- 26816851 TI - Clinical presentation and treatment of bladder pain syndrome/interstitial cystitis (BPS/IC) in India. AB - Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic disease characterized by pelvic pain urgency and frequency. Patients with severe symptoms lead a very miserable life. North American, European and Asian guidelines have been recently promulgated but they differ on many important issues. There is no consensus on its name, definition, investigations and management. Indian guidelines have also been developed and they give more importance to the symptoms in relation to micturition. Though initially believed to be rare or non-existent in India the situation has changed. In Indian patients the presentation is more or less same as the rest of the world but a large percentage have obstructive symptoms and unusual urinary symptoms. Anal discomfort is also common. In India the commonest investigation in all cases of lower urinary tract (LUT) dysfunction is ultrasonography of kidney ureter and bladder with measurement of the post void residual urine volume. Cystoscopy is also done in all the cases to rule out presence of tuberculosis or carcinoma in situ. Bladder pain syndrome/interstitial cystitis (BPS/IC) is not considered to be a clinical disease as it is difficult to rule out all differential diagnosis only from history. Hunner's lesion is very rare. Cystoscopy with hydro distension, oral therapy, intravesical therapy and surgical therapy form the back bone of management. It is difficult to know which treatment is best for a given patient. A staged protocol is followed and all the treatment modalities are applied to the patients in a sequential fashion-starting from the non-invasive to more invasive. Intravesical botox has not been found to be effective and there is no experience with interstim neuromodulation. PMID- 26816852 TI - Sympathetic nervous system and chronic bladder pain: a new tune for an old song. AB - Chronic bladder pain (CBP) patients present with pelvic pain or discomfort during bladder filling, for at least a period of 6 months, which may be accompanied by lower urinary tract symptoms such as frequency, nocturia, and urgency. However, both the etiology of CBP and pathophysiological mechanisms are not well described. A number of clinical and basic animal model findings support involvement of sympathetic nervous system in chronic pain syndromes such as CBP. Examples include sympathetic overactivity and high plasma or urinary catecholamine levels that have a high correlation with nociceptive symptoms. In this review, we explored the current evidence in support of the involvement of sympathetic overactivity in CBP. As bladder inflammation often occurs among subgroups of CBP patients, we discuss the possible role of sympathetic nervous system in mastocytosis as well examples examples of animal models that further support the involvement of sympathetic dysfunction in CBP. As there is substantive evidence for cross-organ sensitization in the pelvis can lead to co morbidity of genitourinary and gastrointestinal dysfunctions, we also include how sympathetic dysfunction may play a role in a number of co-morbid chronic pain syndromes. PMID- 26816853 TI - Treatment of painful bladder syndrome/interstitial cystitis with botulinum toxin A: why isn't it effective in all patients? AB - Botulinum toxin A (BTA) is currently used to treat a variety of painful disorders, including painful bladder syndrome/interstitial cystitis (PBS/IC). However, BTA is not consistently effective in all patients. This may be due to the disparity of causes of pain, but this may also relate to the processes by which BTA exerts anti-nociceptive effects. This review discusses mechanisms by which BTA may inhibit pain and studies of the use of BTA in PSB/IC patients. It is doubtful that any single treatment will effectively control pain in PBS/IC patients, and it is highly probable that multiple strategies will be required, both within individual patients and across the population of PBS/IC patients. The purpose of this review is to discuss those mechanisms by which BTA acts, with the intent that alternative strategies exploiting these mechanism, or work through alternative pathways, can be identified to more effectively treat pain in PBS/IC patients in the future. PMID- 26816856 TI - Mast cell activation syndrome. PMID- 26816855 TI - Intravesical liposome drug delivery and IC/BPS. AB - Intravesical therapy has previously shown to be effective in delaying or preventing recurrence of superficial bladder cancer. This local route of drug administration is now demonstrating promise in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) with the benefit of minimal systemic side effects. Liposomes (LPs) are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core. They can incorporate drug molecules, both hydrophobic and hydrophilic, and vastly improve cellular uptake of these drug molecules via endocytosis. Intravesical LPs have therapeutic effects on IC/BPS patients, mainly due to their ability to form a protective lipid film on the urothelial surface and repair the damaged urothelium. This review considers the current status of intravesical LPs and LP mediated drug delivery for the treatment of IC/BPS. PMID- 26816854 TI - Angiogenic factors, bladder neuroplasticity and interstitial cystitis-new pathobiological insights. AB - Vascular endothelial growth factor (VEGF) is essential for normal embryonic development, and maintenance of adult vascular function. Originally described as a vascular permeability factor, VEGF alters tight cell junctions and contributes to maintenance of bladder permeability. VEGF and its receptors are not only expressed in bladder blood vessels but also in apical cells and intramural ganglia. VEGF receptors are fundamentally altered by inflammation and bladder diseases such as interstitial cystitis (IC). Experimental results indicate that VEGF exerts direct effects on bladder nerve density and function. Regardless of the etiology or initiating cause for IC, it is hypothesized that the urinary bladder responds to injury by increasing the production of VEGF that acts initially as a survival mechanism. However, VEGF also has the capacity to increase vascular permeability leading to glomerulations, edema, and inflammation. Moreover, due to elevated numbers of VEGF receptors in the urothelium, the increased levels of VEGF further increase bladder permeability and establish a vicioCus cycle of disease pathophysiology. PMID- 26816857 TI - Professor Yinglu Guo awarded Distinguished Career Award at Societe Internationale d'Urologie (SIU) 2015. PMID- 26816858 TI - Focused issue on interstitial cystitis/bladder pain syndrome (IC/BPS) 2015: Part 2. PMID- 26816859 TI - In what type of interstitial cystitis/bladder pain syndrome is DMSO intravesical instillation therapy effective? AB - BACKGROUND: Dimethylsulfoxide (DMSO) is the most-used agent for intravesical instillation. We conducted this retrospective clinical study to determine in what type of the interstitial cystitis (IC)/bladder pain syndrome (BPS) DMSO was effective. METHODS: We combined DMSO with hydrodistension in 2003 and from 2004 we performed hydrodistension alone. Hydrodistension had been performed in 7 cases of IC/BPS with Hunner's lesions (H group) and 7 cases of IC/BPS without Hunner's lesions (non-H group), and they served as the control group (C group; n=14). There was also a DMSO group (D group; n=14) that consisted of an H group of 7 cases and an non-H group of 7 cases in which the hydrodistension had been immediately followed by intravesical instillation of 50% DMSO 50 mL. Before, and 2, 6, 12, 18, and 24 months (M) after the intervention, the patients were asked to complete a 4-day frequency-volume chart (FVC) and the O'Leary-Sant IC symptom index (ICSI) questionnaire and IC problem index (ICPI) questionnaire, and to rate their pain on a visual analogue scale (VAS). RESULTS: All parameters were improved after hydrodistension in both the C group and the D group. However, comparison of the C group and D group according to whether Hunner lesions were present showed that there were no significant differences in any of the postoperative parameters between the non-H groups in the C group and D group, but in the H groups, average and maximum voided volume were significantly higher and the ICSI, ICPI, and VAS scores were lower in the D group. Moreover, the significant differences increased with the duration of the postoperative period. CONCLUSIONS: DMSO intravesical instillation therapy was useful in both maintaining and improving the effectiveness of hydrodistension in IC/BPS with Hunner lesions. However, DMSO did not have any particular efficacy in the treatment of IC/BPS in the absence of Hunner lesions. PMID- 26816860 TI - How does interstitial cystitis begin? AB - BACKGROUND: Interstitial cystitis (IC) does not start as an endstage disease, it has a beginning when symptoms are milder, intermittent and the disease is misdiagnosed. To determine how IC develops patients were interviewed on when their symptoms began, what they were and are now as well as the various diagnoses that they received before they were determined to have IC. METHODS: One hundred female IC patients were screened. They filled out a questionnaire asking about the age their disease presented, their initial and current symptoms, what their original diagnoses were, effect of the menstrual cycle and sexual activity on their symptoms and about any relatives with bladder symptoms or a current diagnosis of IC. RESULTS: By age 30, 81% of patients had bladder symptoms, 21% before age 10. The first symptom was frequency in 81%, pain present in 59% and the symptoms were intermittent in 64%. Most common early misdiagnosis was UTI in 74% with 93% reporting negative urine cultures. Sex was painful and causes symptom flares in 82%, symptoms flared the week before the menses in 75%. Most common gynecologic diagnosis was yeast vaginitis, 42%. Urge incontinence was present in 33%. There were 51% that reported bladder symptoms in a first degree female relative. CONCLUSIONS: IC begins primarily with frequency and is intermittent in most patients with symptom flares associated with sexual activity. Pain and urgency incontinence tend to be a later symptoms. When IC flares the most common misdiagnosis is UTI. Symptoms begin before age 30 in most but an IC diagnosis is often not made until age 40. Genetics appear to play a significant role. It is important to consider these facts when evaluating women with "early IC" because correct diagnosis will result in proper therapy and reduced health care costs. PMID- 26816861 TI - A multidisciplinary approach to the evaluation and management of interstitial cystitis/bladder pain syndrome: an ideal model of care. AB - Interstitial cystitis/bladder pain syndrome (IC/BPS) is a complex syndrome that has long been treated with bladder directed therapies, which often fail to address the multiple underlying etiologies that can contribute to this disease process. This disease often involves symptoms that extend beyond the bladder and involve the pelvic floor making it crucial for clinicians to approach the patient using a multidisciplinary team. This article will discuss the underlying etiologies for IC/BPS and describe the multidisciplinary approach which we have found to be extremely successful in managing this patient population. PMID- 26816862 TI - Interstitial cystitis/painful bladder syndrome: diagnostic evaluation and therapeutic response in a private urogynecology unit. AB - BACKGROUND: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a spectrum of pelvic, bladder or urethral pain, as well as irritative voiding symptoms. The term interstitial cystitis (IC) is reserved for patients with typical cystoscopic features. Diagnosis and management of this syndrome may be difficult. The aim of this study was to describe endoscopic features and our experience on the treatment of this syndrome in Urodifem de Occidente S.C., a private urogynecology unit. METHODS: Observational, retrospective analytic study of 25 treated patients from 33 with diagnosis of IC/PBS between January 2001 and March 2015. The diagnosis was done by clinical, cystoscopic and urodynamic approach. Treatment was based on bladder instillation of dymetilsulfoxido (DMSO), dexamethasone and heparin. Oral pentosan polysulphate was prescribed for at least 1 year. RESULTS: Cystoscopic findings showed petechial hemorrhages in 32%, Hunner's lesions in 28%, glomerulations in 28% and bladder pain in absence of lesions in 12%. The basic treatment included one instillation once a week for 6 weeks, twice a month for 2 months and four monthly instillations. Three cases had complete remission of their symptoms, 21 had significant improvement and we have only one failure. CONCLUSIONS: We recommend the combined use of DMSO instillation and pentosan polysulphate (PPS) in cases of IC/PBS. PMID- 26816863 TI - Role of cystoscopy and hydrodistention in the diagnosis of interstitial cystitis/bladder pain syndrome. AB - There are controversies about whether cystoscopy with or without hydrodistention (HD) plays a role in the diagnosis and treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). We reviewed the recommendations of various societies and associations of greater impact in this complex disease, analyzing the indications, technique, findings and complications of this procedure. PMID- 26816864 TI - Review of intravesical therapies for bladder pain syndrome/interstitial cystitis. AB - Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic pain condition characterised by urinary frequency, urgency and pain or discomfort which the patient attributes to the bladder. It is a complex condition to manage and treat and requires a multi-disciplinary and multi-modal approach. As well as lifestyle and behavioural modifications, physical therapy and oral medications, intravesical treatments can be used in the treatment algorithm for BPS/IC. A number of intravesical agents are reviewed in this paper along with the available evidence for their use. PMID- 26816865 TI - Interstitial cystitis/bladder pain syndrome and glycosaminoglycans replacement therapy. AB - Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disease characterized by discomfort or recurrent abdominal and pelvic pains in the absence of urinary tract infections. Its symptomatology includes discomfort, increased bladder pressure, sensitivity and intense pain in the bladder and pelvic areas, increased voiding frequency and urgency, or a combination of these symptoms. For these reasons, this pathology has a very negative impact on quality of life. The etiology of IC/BPS is still not well understood and different hypotheses have been formulated, including autoimmune processes, allergic reactions, chronic bacterial infections, exposure to toxins or dietary elements, and psychosomatic factors. The finding of an effective and specific therapy for IC/BPS remains a challenge for the scientific community because of the lack of a consensus regarding the causes and the inherent difficulties in the diagnosis. The last recent hypothesis is that IC/BPS could be pathophysiologically related to a disruption of the bladder mucosa surface layer with consequent loss of glycosaminoglycans (GAGs). This class of mucopolysaccharides has hydrorepellent properties and their alteration expose the urothelium to many urinary toxic agents. It has been hypothesized that when these substances penetrate the bladder wall a chain is triggered in the submucosa. In order to improve the integrity and function of the bladder lining, GAG layer replenishment therapy is widely accepted as therapy for patients with IC/BPS who have poor or inadequate response to conventional therapy. Currently, Chondroitin sulfate (CS), heparin, hyaluronic acid (HA), and pentosan polysulphate (PPS), and combinations of two GAGs (CS and HA) are the available substances with different effectiveness rates in patients with IC/BPS. There are four different commercially available products for GAG replenishment including CS, heparin, HA and PPS. Each product has different concentrations and dosage formulations. Recently, a combination of CS and HA is the latest commercially available product with promising results. PMID- 26816866 TI - Similarities between interstitial cystitis/bladder pain syndrome and vulvodynia: implications for patient management. AB - Interstitial cystitis/bladder pain syndrome (IC/BPS) and vulvodynia are chronic pain syndromes that appear to be intertwined from the perspectives of embryology, pathology and epidemiology. These associations may account for similar responses to various therapies. PMID- 26816867 TI - The Chinese approach to complementary and alternative medicine treatment for interstitial cystitis/bladder pain syndrome. AB - Management of interstitial cystitis/bladder pain syndrome (IC/BPS) remains a challenge due to poor understanding on its etiology. Complementary and alternative medicine (CAM), as an optional treatment, has been widely used, because no definitive conventional therapy is available. The different domain of CAM provides miscellaneous treatments for IC/BPS, which mainly include dietary modification, nutraceuticals, bladder training, biofeedback, yoga, massage, physical therapy, Qigong, traditional Chinese medicine and acupuncture. Clinical evidence has shown that each therapy can certainly benefit a portion of IC/BPS patients. However, the target patient group of each therapy has not been well studied and randomized, controlled trials are needed to further confirm the efficacy and reliability of CAM on managing IC/BPS. Despite these limitations, CAM therapeutic characteristics including non-invasive and effectiveness for specific patients allow clinicians and patients to realize multimodal and individualized therapy for IC/BPS. PMID- 26816868 TI - Complementary and alternative medical therapies for interstitial cystitis: an update from the United States. AB - The diagnosis and treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) has shifted from organ-specific to a multifactorial, multidisciplinary and individualized approach. Patients with refractory and debilitating symptoms may respond to complementary and alternative medical treatments (CAM). Through CAM therapies, practitioners assist the patient to be at the center of their care, empowering them to be emotionally and physically involved. Multi disciplinary care, including urology, gynecology, gastroenterology, neurology, psychology, physiotherapy and pain medicine, is also identified to be the crux of adequate management of patients with chronic pelvic pain because of its variable etiology. The purpose of this review is to emphasize these changes and discuss management strategies. PMID- 26816869 TI - Current guidelines in the management of interstitial cystitis. AB - Interstitial cystitis (IC) is a heterogeneous chronic disease of unknown etiology that impacts a very large number of women. Symptoms are highly variable: patients may suffer from pelvic pain that is exacerbated by bladder filling, and can be associated with a variety of lower urinary tract symptoms including frequency and urgency. Given the varying presentations and severities of corresponding treatment must be tailored to each specific patient. Current American Urological Association (AUA) guidelines separate the IC treatment recommendations into six tiers of increasing invasive therapies. These treatment guidelines begin with education and lifestyle modifications and progress through levels of physical, pharmacological, and ultimately surgical therapies for those that fail the less invasive therapies. The purpose of this review is to outline the recommendations for the treatment of IC and the evidence from which these recommendations arise. Furthermore, we examine the most up to date literature so that we may recognize future directions in the treatment of IC. PMID- 26816870 TI - Professor Run Wang: can erectile dysfunction be cured? PMID- 26816871 TI - Thyroid dysfunction and subfertility. AB - The thyroid hormones act on nearly every cell in the body. Moreover, the thyroid gland continuously interacts with the ovaries, and the thyroid hormones are involved in almost all phases of reproduction. Thyroid dysfunctions are relatively common among women of reproductive age, and can affect fertility in various ways, resulting in anovulatory cycles, high prolactin levels, and sex hormone imbalances. Undiagnosed and untreated thyroid disease can be a cause of subfertility. Subclinical hypothyroidism (SCH), also known as mild thyroid failure, is diagnosed when peripheral thyroid hormone levels are within the normal reference laboratory range, but serum thyroid-stimulating hormone levels are mildly elevated. Thyroid autoimmunity (TAI) is characterized by the presence of anti-thyroid antibodies, which include anti-thyroperoxidase and anti thyroglobulin antibodies. SCH and TAI may remain latent, asymptomatic, or even undiagnosed for an extended period. It has also been demonstrated that controlled ovarian hyperstimulation has a significant impact on thyroid function, particularly in women with TAI. In the current review, we describe the interactions between thyroid dysfunctions and subfertility, as well as the proper work-up and management of thyroid dysfunctions in subfertile women. PMID- 26816872 TI - The prevalence of positive urinary cotinine tests in Korean infertile couples and the effect of smoking on assisted conception outcomes. AB - OBJECTIVE: Smoking has been reported to harm nearly every organ of the body, but conflicting results have been reported regarding the effects of smoking on assisted conception. In this prospective cohort study, we aimed to investigate the prevalence of positive urinary cotinine tests in infertile couples and whether cotinine positivity was associated with infertility treatment outcomes. METHODS: A qualitative urinary cotinine test was administered to 127 couples who underwent in vitro fertilization (IVF, n=92) or intrauterine insemination (IUI, n=35). RESULTS: The overall prevalence of positive urinary cotinine test was 43.3% (55/127) in the male partners and 10.2% (13/127) in the female partners with similar prevalence rates in both genders in the IUI and IVF groups. Semen characteristics, serum markers of ovarian reserve, and number of retrieved oocytes were comparable among cotinine-positive and cotinine-negative men or women (with the exception of sperm count, which was higher among cotinine positive men). The results of urinary cotinine tests in infertile couples were not associated with IVF and IUI outcomes. CONCLUSION: The presence of cotinine in the system, as indicated by a positive urinary cotinine test, was not associated with poorer outcomes of infertility treatment. PMID- 26816873 TI - Anti-Mullerian hormone levels as a predictor of clinical pregnancy in in vitro fertilization/intracytoplasmic sperm injection-embryo transfer cycles in patients over 40 years of age. AB - OBJECTIVE: The aim of the current study was to determine the predictive value of anti-Mullerian hormone (AMH) levels for pregnancy outcomes in patients over 40 years of age who underwent in vitro fertilization or intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles. METHODS: We retrospectively analyzed the medical records of 188 women aged 40 to 44 years who underwent IVF/ICSI-fresh ET cycles due to unexplained infertility in the fertility center of CHA Gangnam Medical Center. Patients were divided into group A, with AMH levels <1.0 ng/mL (n=97), and group B, with AMH levels >=1.0 ng/mL (n=91). We compared the clinical pregnancy rate (CPR) in the two groups and performed logistic regression analysis to identify factors that had a significant effect on the CPR. RESULTS: The CPR was significantly lower in group A than group B (7.2% vs. 24.2%, p<0.001). In multivariate logistic regression analysis, AMH levels were the only factor that had a significant impact on the CPR (odds ratio, 1.510; 95% confidence interval, 1.172-1.947). The area under the receiver operating characteristic curve for AMH levels as a predictor of the CPR was 0.721. When the cut-off level of AMH was set at 1.90 ng/mL, the CPR was 6.731-fold higher in the group with AMH levels >=1.90 ng/mL than in the group with AMH levels <1.90 ng/mL (p<0.001). CONCLUSION: Our study showed that AMH levels were predictive of clinical pregnancy in infertility patients over 40 years of age. Further prospective studies should be conducted to validate the predictive capability of AMH levels for the outcome of clinical pregnancy. PMID- 26816874 TI - A high response to controlled ovarian stimulation induces premature luteinization with a negative impact on pregnancy outcomes in a gonadotropin-releasing hormone antagonist cycle. AB - OBJECTIVE: The goal of this study was to investigate the relationship between serum progesterone (P4) levels on the day of human chorionic gonadotropin (hCG) administration and the pregnancy rate among women undergoing controlled ovarian stimulation for in vitro fertilization (IVF) or intracytoplasmic sperm injection embryo transfer (ICSI-ET) using a flexible antagonist protocol. METHODS: This prospective study included 200 IVF and ICSI-ET cycles in which a flexible antagonist protocol was used. The patients were divided into five distinct groups according to their serum P4 levels at the time of hCG administration (0.80, 0.85, 0.90, 0.95, and 1.00 ng/mL). The clinical pregnancy rate (CPR) was calculated for each P4 interval. Statistically significant differences were observed at a serum P4 level of 0.9 ng/mL. These data suggest that a serum P4 concentration of 0.9 ng/mL may represent the optimal threshold level for defining premature luteinization (PL) based on the presence of a significant negative impact on the CPR. RESULTS: The CPR for each round of ET was significantly lower in the PL group defined using this threshold (25.8% vs. 41.8%; p=0.019), and the number of oocytes retrieved was significantly higher than in the non-PL group (17.3+/-7.2 vs. 11.0+/-7.2; p=0.001). Elevated serum P4 levels on the day of hCG administration were associated with a reduced CPR, despite the retrieval of many oocytes. CONCLUSION: Measuring serum P4 values at the time of hCG administration is necessary in order to determine the optimal strategy for embryo transfer. PMID- 26816875 TI - Alterations in uterine hemodynamics caused by uterine fibroids and their impact on in vitro fertilization outcomes. AB - OBJECTIVE: To investigate the impact of fibroids on the blood flow of the uterine and subendometrial arteries and in vitro fertilization (IVF) outcomes. METHODS: In this study, we analyzed 86 IVF/intracytoplasmic sperm injection (ICSI) cycles in which a gonadotropin-releasing hormone antagonist protocol was used for controlled ovarian stimulation between January 2008 and March 2009. The subjects comprised 86 infertile women with (fibroid group, n=43) or without (control group, n=43) uterine fibroids. RESULTS: Patient characteristics were similar between the fibroid and control groups. The IVF/ICSI outcomes in patients with fibroids were similar to those of patients in the control group. The resistance index (RI) and pulsatile index (PI) of the uterine and subendometrial arteries on the day of embryo transfer were also comparable between the two groups. IVF outcomes and uterine hemodynamics in patients with multiple (>=2) fibroids were similar to those of patients with a single fibroid. However, clinical pregnancy and implantation rates were significantly lower in patients with fibroids who experienced uterine cavity distortion than in patients with fibroids who had a normal uterine cavity (both p<0.05). The RI and PI of the subendometrial artery were significantly higher on the day of embryo transfer in patients with fibroids who experienced uterine cavity distortion than in patients with fibroids who had a normal uterine cavity (both p<0.05). CONCLUSION: Fibroids which distorting the uterine cavity might impair the subendometrial artery blood flow clinical pregnancy rate and embryo implantation rate in infertile patients undergoing IVF. Otherwise, IVF outcomes were not influenced by the presence of uterine fibroids. PMID- 26816876 TI - Multiple pregnancy after single or multiple embryo transfer performed according to Korean guidelines. AB - OBJECTIVE: To assess compliance with Korean guidelines for embryo transfer, the possible reasons for non-compliance, and multiple pregnancies according to each specific condition in compliant cycles. METHODS: A single-institution, retrospective study was conducted of 256 fresh in vitro fertilization cycles during 2012-2014. To assess compliance with Korean guidelines, the maximum recommended number of embryos transferred (according to criteria of age, transfer day, and presence of favorable conditions) was compared with the actual number of embryos transferred. Clinical pregnancy rate (PR) was assessed as the percentage of pregnant women resulting from each set of transfer conditions, including the number of embryos transferred. The multiple pregnancy rate (MPR) was calculated as the percentage of pregnant women with a multifetal pregnancy. RESULTS: The compliance rate with the Korean guidelines was 96.5% (247/256). Non-compliance occurred in nine cycles owing to poor embryo quality, repeated implantation failure, or hostile endometrium. In compliant cycles, the PR was 31.2% (77/247), and the MPR was 27.3% (21/77; 20 twins and one triplet). Higher MPR was noted in two types of transfer conditions: transfer of three cleavage embryos in women aged 35-39 years with favorable conditions (66.7%; primarily from those aged 35 37 years) and transfer of two blastocysts in women aged >=40 years with favorable conditions (50%). CONCLUSION: Under the Korean guidelines, compliance rate was high in our center. Multiple pregnancies occurred primarily in group with favorable conditions. In high-risk groups for multiple pregnancies, reducing number of embryos transferred should be considered than suggested in the guideline. PMID- 26816877 TI - Dermatoglyphs in Coronary Artery Disease Among Ningxia Population of North China. AB - BACKGROUND: Coronary artery disease (CAD) is an enormous health problem in the world. Dermatoglyphs are cutaneous ridges on the fingers, palms, and soles, formed by genetic regulation and control during early intrauterine life. The Dermatoglyphic traits do not change significantly as the growth of the age. They may be the phenotypic characters of individual genes and represent the predisposition to certain diseases. AIMS AND OBJECTIVES: The study was carried out to document characteristic dermatoglyphic patterns in coronary artery disease which could be useful in early diagnosis of the disease. MATERIALS AND METHODS: Dermatoglyphic study of 258 male (129 coronary artery disease cases and 129 normal subjects) of Ningxia China were studied in the present cross-sectional study. It involved the digital patterns, ATD angles, A-B ridge counts on the hands. Chi-square test, t-test were used for the statistical analysis in this study. RESULTS: The overall frequency of whorls was higher followed by loop and arch in both two groups. It was observed that there was significant difference of digital frequency of whorls and ulnar loops in patients in both hands as compared to controls (p<=0.01). The mean value of finger ridge counts, total ridge counts were similar between two groups. The A-B ridge counts were significantly higher in coronary artery disease compared with controls on the right palm (p<=0.01). However, the mean ATD angle values were significantly higher in cases than those of in normal on both hands (p<0.05). CONCLUSION: Abnormally high A-B ridge count, ATD angles and the frequency of whorls are characteristic dermatoglyphic patterns of coronary artery disease. Dermatoglyphics may have an important role in early diagnosis of coronary artery disease in future. PMID- 26816878 TI - Pulmonary Sequestration: A 29 Patient Case Series and Review. AB - INTRODUCTION: Pulmonary sequestration also known as bronchopulmonary sequestration is a rare disease, with very few case series reviewed in literature. In this study, we review the demographics, presentation, imaging and treatment of pulmonary sequestration in 29 patients from our institution, and provide comparison data from previously published series with an overview of the disease history. MATERIALS AND METHODS: Records reviewed for all patients evaluated and treated in our institution with a pathological proven diagnosis of pulmonary sequestration from January 2004 through December 2013. Collected data included demographics, clinical presentation, diagnostic imaging, location of the lesion, type of sequestration, and subsequent treatment. RESULTS: Of the 29 patients reviewed 8 (28%) were children 0-2 years, 1 adolescent age 17, and 20 (69%) adults 21-70 years with a mean age of 42 among adults. Systemic arterial supply to the sequestered segment was demonstrated with computed tomographic angiography (CTA) in 25 patients (86%). In 19 patients (66%), the sequestered segment was located in the left lower lobe, and 16 (55%) were intralobar. CONCLUSION: Diagnostic delays of pulmonary sequestration were common among the adult population as the presenting symptoms often mimicked other common pulmonary diseases, such as pneumonia and asthma. These findings were consistent among previously published series. CTA was the preferred imaging modality for preoperative planning with high sensitivity and specificity in identifying the lesion. PMID- 26816879 TI - Assessing the Validity of Friedewald's Formula and Anandraja's Formula For Serum LDL-Cholesterol Calculation. AB - INTRODUCTION: An important aspect of the assessment of cardiovascular risk for a dyslipidemic subject is the estimation of serum Low-Density Lipoprotein Cholesterol (LDL-C). There are many homogenous assays currently available for the estimation of serum LDL-C. Most clinical laboratories determine LDL-C (mg/dL) by Friedewald's formula (FF), LDL-C = (TC) - (HDL-C) - (TG/5). Recently Anandaraja and colleagues have derived a new formula for calculating LDL-C, AR-LDL-C = 0.9 TC- (0.9 TG/5)-28. AIM & OBJECTIVES: The aim of the study was: a) to determine if, and to what extent, LDL-C level was underestimated/overestimated when it was calculated using the formulae compared with direct measurement of LDL-C, and b) to determine which of the calculated formulae show maximum correlation with direct LDL cholesterol method at different TG levels. SETTING & DESIGN: A cross sectional study. MATERIALS AND METHODS: Record analysis was done from the 370 (TG <400mg/dl) lipid profile reports of patients above 18 years. LDL-C estimation was done by homogenous assay and also calculated using the Friedewald's Formula and Anandaraja's Formula. RESULTS: The mean LDL-C levels were 105.17+/- 43.4, 102.98 +/-42.5, and 98.20 +/-43.7 mg/dl for D-LDL-C, F-LDL-C and AR-LDL-C, respectively. A good correlation was found between the calculated LDL-C methods and Direct Low Density Lipoprotein Cholesterol method (D-LDL-C) assay, that is, F-LDL-C versus D LDL-C (r = 0.937) and AR-LDL-C versus D-LDL-C (r= 0.918). Bland-Altman plot for FF-LDL-C & AR-LDL-C showed minimal negative bias. CONCLUSION: FF-LDL-C correlated maximally with D-LDL-C estimation at all levels of triglycerides except at TG < 100mg/dl. At TG < 100mg/dl, Anandaraja's Formula works better. FF-LDL-C can be used in place of D-LDL-C when the direct method cannot be afforded. PMID- 26816880 TI - Serum Zinc and Metabolic Health Status in Siblings of Patients with Type 2 Diabetes Mellitus. AB - INTRODUCTION: There is increasing evidence on the association between lower serum zinc levels and metabolically unhealthy status in normal weight individuals'. AIM: Our aim was to investigate serum zinc levels in a sample of siblings of patients with type 2 diabetes mellitus and to ascertain its relation with metabolic syndrome components. MATERIALS AND METHODS: Serum zinc was determined in 331 apparently healthy individuals, 201 were siblings of patients with type 2 diabetes mellitus (type 2 DM) and 130 individuals with negative family history of diabetes (healthy controls), with age range 20-40 years. The association between components of metabolic syndrome and serum zinc levels was examined. RESULTS: The siblings of patients with type2 DM exhibited significantly lower serum zinc levels than did the healthy controls (94.1+/-20.8 ug/dl vs. 103.2+/-15.6 ug/dl, p=0.012). The mean serum zinc levels were lower in siblings exhibited higher levels of waist circumference, fasting blood glucose and triglycerides. Those categorized as metabolically obese, normal weight (MONW) exhibited lower serum zinc levels than did the non-MONW, but the difference was not significant (93.7+20.9 ug/dl vs. 96.2+18.1ug/dl, p=0.059). The correlation between serum zinc levels and fasting blood glucose was inverse among the siblings (r=- 0.233, p=0.001). CONCLUSION: A low zinc status is present in 13.9% of the siblings of patients with type 2 DM, particularly among MONW individuals. This finding may have clinical implications due to the increased risk of future metabolic disease. PMID- 26816881 TI - Serum Copper as a Marker of Disease Activity in Rheumatoid Arthritis. AB - INTRODUCTION: Copper is an important trace element for normal growth and development of the body. It is also essential for maturation of collagen tissues. The purpose of the study was to estimate the serum copper levels in rheumatoid arthritis patients and to see its association with the various parameters of disease activity. MATERIALS AND METHODS: The study was carried out among 50 diagnosed rheumatoid arthritis patients (25 each of active disease & remission patients) and 50 age and sex matched controls. Fasting blood sample was collected for estimation of serum copper, haemoglobin level and ESR in the subjects. RESULTS: Mean serum copper level in the case group was found to be significantly higher than that of the control group (p-value<0.001). This increase of copper level was more in active disease than those with remission (p-value < 0.0001). A significant positive correlation was found between serum copper level and ESR, serum copper level and morning stiffness and a negative correlation was found between serum copper level and haemoglobin level in rheumatoid arthritis patients. CONCLUSION: In rheumatoid arthritis patients, serum copper level may be used as an additional biochemical marker for estimation of disease activity. PMID- 26816882 TI - An Infant with Chronic Diarrhoea and Failure to Thrive: Familial Hypobetalipoproteinemia. AB - Diarrhoea is a common clinical problem for treating clinicians in developing countries. Mostly, it is attributed to malnutrition and infection. We, as clinicians, tend to miss some of cases who have inherited enteropathies because of lack of suspicion and non availability of diagnostic facilities. Here, we report a case of homozygous hypobetalipoproteinaemia in a nine-month-old female patient presenting with chronic diarrhoea and failure to thrive. Simple parental screening of lipid parameters led to correct diagnosis and early intervention in present case. PMID- 26816883 TI - Impact of Quantified Smoking Status on Cognition in Young Adults. AB - INTRODUCTION: Cigarette smoking is an addictive behaviour which continues to rise among young adults. It has been associated with various health hazards. Effect of smoking on cognitive function has been contradicting. Thus our aim was to compare cognitive performances between smokers and non smokers and also to observe the effect of varying intensity of smoking on cognition. MATERIALS AND METHODS: This is a cross-sectional study. Thirty non smokers, 30 mild smokers, 30 moderate smokers, 30 heavy smokers within the age group of 25-35 years were involved in the study. Their cognitive performance were assessed by digit symbol substitution test (DSST), digit vigilance test (DVT), visual reaction time (VRT), letter cancellation test (LCT), word recall (WR), and object recall (OR). RESULT: The cognitive data were analysed using unpaired students t-test and ANOVA in SPSS 19. Smokers showed significant decline in their cognitive performances when compared to smokers (p <= 0.05). Mild smokers showed significantly better performance in the DSST, DVT and VRT tests than the non smokers. This indicates the attention and alertness were better in mild smokers than the non smokers. With the increase in the intensity of smoking cognitive performances were also significantly declined. CONCLUSION: Thus the study indicates decreased cognitive performances in young adult smokers. PMID- 26816884 TI - Is Video Podcast Supplementation as a Learning Aid Beneficial to Dental Students? AB - INTRODUCTION: Podcasting has recently emerged as an important information technology tool for health professionals. Podcasts can be viewed online or downloaded to a user computer or a handheld multimedia device like a portable MP3 player, smart phone and tablet device. The principal advantage of the podcast is that the presentation of information need not be linked with any particular time or location. Since students are familiar with newer technology tools and may be using it on a regular basis, video podcast could serve as a convenient tool for students to help remember both conceptual and factual information. AIM: The purpose of this study was to assess the attitude of first year dental students towards video podcast supplementation and to assess the efficacy of video podcast as a teaching aid in comparison to text book reading. MATERIALS AND METHODS: First year dental students were recruited for this study. A didactic lecture class was conducted for the students (n=100). The students were then randomly divided into two groups. Students present in group A (n=46) underwent a video podcast session followed by a multiple choice question test. This was followed by student feedback to assess the usefulness of video podcast. Students belonging to group B (n=54) had a study session for 20 minutes followed by the MCQ test. Students then underwent the video podcast session followed by feedback to assess the utility of video podcast. Mann-Whitney U test was applied to compare the difference in the median MCQ score between the two groups. RESULTS: The findings revealed a significant gain in the median MCQ score in the intervention group (group A) when compared to control group (Group B). In the feedback form, 89% of students agreed that the video podcast might be useful as it would enable them to view slides and hear the lectures repeatedly. CONCLUSION: Students who underwent the video podcast session performed significantly better in the MCQ test compared to students who underwent text book reading alone. This demonstrates an advantage of video podcasts over text book reading. Majority of students accepted the benefits of video podcast supplementation. PMID- 26816885 TI - Perception of Medical Faculties towards Early Clinical Exposure and MCI Vision 2015 Documents in Western Maharashtra. AB - INTRODUCTION: The Medical Council of India (MCI) has advocated early clinical exposure for students in medical colleges. In its 'Vision-2015' document for further reforms in undergraduate medical education, the MCI underlined the need for clinical teaching from first year onwards in medical colleges. AIM: Our aim was to collect and analyse perception of medical faculties towards early clinical exposure and MCI Vision 2015 and to study the awareness, depth and interest among medical faculties towards these changes. MATERIALS AND METHODS: We used 10-item self developed survey questionnaires, which was validated from experts in medical education. 10-item questionnaire was based on awareness, depth and interest among medical faculties towards early clinical exposure and MCI Vision 2015 documents released by MCI in 2011. Qualitative data was assessed using percentage scale. We were approached to 182 preclinical medical faculties, however responses were received from 127 medical faculties from first year medical course subjects from six different college's viz. two from Deemed University, two from Government sector and two from private sector but affiliated to Maharashtra University of Health sciences, Nasik, India. RESULTS: A 94.48% faculty members were aware regarding MCI Vision 2015 documents released by MCI in 2011. Average 12% faculties could answer specific approach MCQs based on MCI Vision 2015 documents. However, 82.67% faculties agreed early clinical exposure will be definitely helpful if implemented in curriculum. CONCLUSION: The present work underlines need of special coaching and attention towards this important issue in medical education. PMID- 26816886 TI - Molecular Identification of Clinical Isolates of Mycobacterium fortuitum by Random Amplified Polymorphic DNA (RAPD) Polymerase Chain Reaction and ERIC PCR. AB - BACKGROUNDS: Non tuberculous mycobacteria (NTM) are of importance now-a-days due to their increasing virulence outbreaks and emerging antibiotic resistance. Since the most common NTM in Iran is reportedly Mycobacterium fortuitum, the present study was designed with the aim of molecular identification of clinical isolates of M. foruitum to analyse their heterogeneity. MATERIALS AND METHODS: A total of 81 isolates of NTM isolated from various samples were collected. The clinical isolates were assigned to species M. fortuitum by using conventional and molecular methods. The DNA banding patterns of ERIC- PCR and RAPD- PCR were analysed by using Bionumeric 7.5 software. RESULTS: Out of 81 tested NTM, 36 strains of M. fortuitum were identified. 33 isolates were selected for molecular typing in this study. Based on RAPD and ERIC analysis, M. fortuitum isolates were divided into 3 and 6 clusters, respectively. Most of the isolates were distributed into types of II RAPD (20 members/ 60.6 %) and V (14 members/ 42.4% with sub cluster I & II) of ERIC. In RAPD analysis, the major fragments were 300 bp, followed by fragment 1000. In ERIC analysis, the major fragments were 280 bp followed by fragment 1200 bp. CONCLUSION: In conclusion, though the results from this study represented higher discriminatory power of ERIC, however the combination of RAPD and ERIC analysis were able to sufficiently discriminate the genotypic diversity, infection control, and gain useful epidemiological information regarding M. fortuitum isolates. PMID- 26816887 TI - Fosfomycin: An Alternative Therapy for the Treatment of UTI Amidst Escalating Antimicrobial Resistance. AB - INTRODUCTION: Urinary tract infections (UTIs) are the most commonly encountered infectious diseases. The current study was undertaken with a dual purpose, to provide an insight into the current scenario of the microorganisms causing UTI, their antimicrobial sensitivity patterns and also try and evaluate the activity of fosfomycin against E. coli, both ESBL producers as well as non-producers. MATERIALS AND METHODS: The study was conducted prospectively in the Department of Microbiology of a tertiary care hospital from January to June 2014. A total of 358 isolates from the urinary samples of the patients with a diagnosis of urinary tract infection were included in the study. Antibiotic sensitivity testing and extended spectrum beta lactamase (ESBL) production testing was done as per CLSI guidelines. RESULTS: These represented 297 (82.9%) gram-negative isolates and 61 (17%) gram-positive isolates. The 297 gram-negative isolates represented 265 (89.2%) members of the Enterobacteriaceae, 185 (69.8%) of which were Escherichia coli, 66 (24.9%) Klebsiella spp. and 14 (5.28%) Proteus spp. Non-fermentative Pseudomonas spp were isolated from 8.9% cases. Amongst the Gram negative isolates tested, 78 (21.8%) formed extended spectrum beta-lactamases. Of the total 358 isolates tested, 338 (94.4%) were found to be susceptible to fosfomycin. CONCLUSION: Fosfomycin showed good activity against both ESBL-producing and ESBL negative E. coli isolates. The main finding of our study is that fosfomycin exhibits excellent antimicrobial activity even against the isolates with relatively high levels of antimicrobial resistance and hence can be a useful drug in our armamentarium. PMID- 26816888 TI - Hepatitis C Virus (HCV) Infection among Seronegative Patients undergoing Haemodialysis in a Remotely Located Tertiary Care Hospital of Northern India: Value of HCV-RNA and Genotypes. AB - BACKGROUND: Haemodialysis (HD) patients are at an increased risk of Hepatitis C virus (HCV) infection, which is significantly associated with increased morbidity and mortality. AIM: The aim of this study was to find the prevalence of HCV infection in anti-HCV antibody negative haemodialysis patients by Real-time PCR (RT-PCR) and value of HCV-RNA among seronegative patients undergoing haemodialysis in a remotely located tertiary care hospital. MATERIALS AND METHODS: A total of 100 chronic renal failure patients on haemodialysis were studied. All the patients were screened for anti-HCV antibodies by ELISA test and for HCV-RNA by RT-PCR. RESULTS: The overall prevalence of HCV infection was 32%. Antibody positivity was 30% and HCV-RNA by RT-PCR was detected in 20%. HCV-RNA in seronegative patients was detected in 2.8%. CONCLUSION: Serological assays (30%) are quite reliable for detecting HCV infection in patients undergoing haemodialysis in our tertiary care hospital. Only a small proportion of them (2.8%) require the documentation of viral genome for current infection. PMID- 26816889 TI - The Frequency, Causes and Prevention of Needlestick Injuries in Nurses of Kerman: A Cross-Sectional Study. AB - INTRODUCTION: The needlestick injuries can cause the transmission of infectious diseases. Compared to other members of the community of health care nurses are at great risk of needle stick injury because of their frequent performance with vein punctures and taking care of patients suffering from different infectious diseases. AIM: The main aim of this study was to assess Prevalence, causes and preventive of Needle Sticks injuries among nurses in Kerman (south of Iran). MATERIALS AND METHODS: This cross-sectional study was conducted from December 2014 to March 2015 on 240 nurses employed in two hospitals of Kerman. Sampling was performed through simple random sampling. Data gathered through a researcher made questioner. Data analysed by use descriptive analytical testes. RESULTS: From the nurses' perspective the main physical and human causes of needlestick injuries were syringe needles (82) and crowded wards (74). The majority of the nurses believed the most effective method to prevent needlestick were training (82). CONCLUSION: Due to the high prevalence of injuries caused by sharp objects in nurses, needlestick injuries are suggested to be recorded in special forms and their causes to be checked by the Infection Control Committee. Since syringe needle heads and angiocatheter are the main causes of needlestick injuries, providing safe medical equipment should also be emphasized. PMID- 26816890 TI - Fluconazole Resistant Candida Oesophagitis in Immunocompetent Patients: Is Empirical Therapy Justifiable? AB - INTRODUCTION: C. albicans (Candida albicans) is the foremost cause of fungal oesophagitis, however other species such as Candida tropicalis, Candida krusei and Candida stellatoidea have also been implicated to cause this condition. Although, numerous studies have identified risk factors for C. albicans oesophagitis, data for non- C. albicans species is still sparse. AIM: To determine the aetiology of Candida oesophagitis in our medical centre over a two year period. Additionally, to investigate predisposing conditions for oesophageal candidiasis caused by different Candida species. MATERIAL AND METHODS: All consecutive patients posted for upper gastrointestinal endoscopy at the endoscopy unit of a tertiary care hospital in north India with findings consistent with oesophagitis were screened for the presence of Candida oesophagitis by performing KOH (potassium hydroxide) examination and culture on SDA (Sabouraud's dextrose agar). Antifungal susceptibility testing as per CLSI guidelines was performed for fluconazole, a most common empirically prescribed antifungal for the condition. RESULTS: A total of 1868 patients with no known immune-compromised condition underwent upper gastroscopy at our centre during the study period. The prevalence of Candida oesophagitis was 8.7% (n = 163). C. albicans was recovered from majority of infections (52.1%), followed by C. tropicalis (24%), C. parapsilosis (13.4%), C. glabrata (6.9%) and C. krusei (3.6%). Alarmingly, among the C. albicans isolates 8.6% were resistant to fluconazole. CONCLUSION: With rising reports of antifungal drug resistance among the isolates of Candida species, an increasing prevalence of this organism could have an impact on the treatment of Candidal oesophagitis and it should be approached with caution by the clinician. PMID- 26816891 TI - Non Diphtheritic Corynebacteria: An Emerging Nosocomial Pathogen in Skin and Soft Tissue Infection. AB - INTRODUCTION: Non-diphtheritic corynebacteria are normal inhabitants of skin and mucous membrane. When isolated from clinical specimens they are often considered as contaminants. Recent reports suggest their role as emerging nosocomial pathogens. AIM: To speciate non-diphtheritic corynebacteria isolated from wound specimens, to correlate their clinical significance and to determine their invitro antimicrobial susceptibilities to 9 antimicrobial agents. MATERIALS AND METHODS: Twenty five non-diphtheritic corynebacteria from skin and soft tissue infections were selected for study. Isolates were identified by battery of tests and minimum inhibitory concentration (MIC) was detected by Clinical & Laboratory Standards Institute (CLSI) described broth microdilution method. MIC was interpreted according CLSI and British Society for Antimicrobial Chemotherapy (BSAC) guidelines. RESULTS: C. amycolatum was the predominant species (20%) followed by C. striatum (16%). Penicillin was least effective invitro followed by clindamycin and ciprofloxacin. Excellent activities were shown by vancomycin, linezolid and imipenem. Multidrug resistance was found in all the species. CONCLUSION: Non-diphtheritic corynebacteria are potential nosocomial pathogens among acute/chronic complicated skin and soft tissue infection. Vancomycin or linezolid can be used empirically to treat such infections until the invitro susceptibility results are available. PMID- 26816892 TI - Aetiologies of Acute Undifferentiated Febrile illness in Adult Patients - an Experience from a Tertiary Care Hospital in Northern India. AB - INTRODUCTION: Acute undifferentiated febrile illness (AUFI) is a common clinical entity in most of the hospitals. The fever can be potentially fatal if the aetiology is not recognized and appropriately treated early. AIM: To describe the aetiology of fever among patients in a tertiary care hospital in Northern India. MATERIALS AND METHODS: A one-year retro-prospective, observational study was conducted in adults (age>18years) presenting with undifferentiated febrile illness (of duration 5-14 days). Diagnosis was confirmed by suitable laboratory tests after exhaustive clinical examination. RESULTS: A total of 2547 patients with AUFI were evaluated. Of these, 1663 (65.3%) were males and 884 (34.7%) were females. Dengue (37.54%); enteric fever (16.5%); scrub typhus (14.42%); bacterial sepsis (10.3%); malaria (6.8%); hepatitis A (1.9%); hepatitis E (1.4%); leptospirosis (0.14%); were the main infections while no specific diagnosis could be delineated in 11%. Mixed infections were noted in 48 (1.9%) patients. CONCLUSION: A good clinical acumen supported by the basic investigations can help diagnose the cause of fever with reasonable certainty. PMID- 26816893 TI - Corynebacterium amycolatum: An Unexpected Pathogen in the Ear. AB - Non-diphtheritic Corynebacteria are now being increasingly recognised as the causative agents of various infections. Among these organisms, Corynebacterium amycolatum is the most frequently isolated one. It has been isolated from urine, pus, catheter tips, blood, prostatic secretion, cerebrospinal fluid and sputum. However, to the best of our knowledge, there are no reports on its role in ear infections. Here, we present 12 cases of ear infection with C.amycolatum. A high index of suspicion is necessary for identification of these gram positive bacilli as they resemble other Corynebacterium species on gram stain. They have metachromatic granules which can be demonstrated by Albert's stain and form characteristic dry, flat colonies on blood agar. These organisms are frequently resistant to ceftriaxone and imipenem. In our study, among the 12 isolates, eight isolates were resistant to ceftriaxone and four to imipenem and two were intermediately susceptible to ceftriaxone although all the 12 strains were uniformly susceptible to vancomycin. All the isolates were negative for toxA and toxB genes by PCR. Genomic sequencing of two isolates confirmed them as C.amycolatum. C.amycolatum is a relatively rare cause of pyogenic ear infections. As it demonstrates more antibiotic resistance than other similar organisms, careful identification with antibiotic susceptibility testing is required in managing these infections. PMID- 26816894 TI - The Prognostic Significance of Neuroendocrine Differentiation in Colorectal Carcinomas: Our Experience. AB - INTRODUCTION: Neuroendocrine differentiation in colorectal carcinomas, detected using immunohistochemistry and ultrastructural techniques, has been studied as a prognostic marker for invention of targeted therapy. There are a few studies done on this aspect which have shown conflicting results ranging from poor prognosis to no prognostic significance. AIM: The aim of the study was to determine the clinical significance of neuroendocrine differentiation in colorectal carcinomas using immunohistochemical stains such as chromogranin A & synaptophysin in relation to its prognostic significance. MATERIALS AND METHODS: A retrospective study was conducted wherein all the colorectal carcinomas, received in the Department of Pathology, over a period of 3 years, were reviewed. Neuroendocrine markers were done on 53 cases of moderately, poorly and undifferentiated adenocarcinomas. Based on the degree of immunoreactivity for these markers, tumours were divided into group 0, group 1, group 2, group 3 & group 4. Group 0 & 1 were categorized as neuroendocrine differentiation absent & group 2, 3 & 4 as present. Neuroendocrine differentiation was correlated with age, sex, grade, stage, diagnosis & survival. Follow up data of the cases was recorded. RESULTS: Neuroendocrine differentiation was present in 18 cases (33.9%). The degree of immunoreactivity for neuroendocrine markers in present study were; group 0- 58%, 1- 7.5%, 2- 9%, 3- 13% & 4- 11%. The mean age of patients was 54 years with a slight male preponderance {M:F::1.6:1}. Most of the carcinomas with neuroendocrine differentiation belonged to Grade II (61%) & Stage II & III (83%). Neuroendocrine differentiation did not show any significant association with age, sex, location, histological type, grade, stage & survival. CONCLUSION: The above results indicate that the presence of neuroendocrine differentiation cannot be recommended as a prognostic marker in colorectal carcinomas. PMID- 26816895 TI - Eosinophilic Structure: Should it be Included in Routine Cytology Reporting of Tuberculosis Lymphadenitis? AB - INTRODUCTION: Fine needle aspiration cytology is a simple, rapid procedure routinely employed for the diagnosis of tuberculosis lymphadenitis. Positivity for acid fast bacilli (AFB) in Ziehl-Neilsen stained smear is still considered as gold standard for diagnosis of Tuberculosis, but all lesions may not yield AFB, thus pose diagnostic problems. Few cytomorphological changes i.e. Eosinophilic structure (ES) in the stained smears correlates with the presence of AFB thus, helping us in rapid diagnosis. AIM: To evaluate the correlation between AFB and ES in necrotic lymph node aspirates. MATERIALS AND METHODS: This is a retrospective study conducted from January to December 2014. Lymphnodes upon purulent aspiration which were reported as granulomatous lymphadenitis suggestive of tuberculosis were included in the study. All the stained smears (H&E, MGG and ZN Stains) for each case were retrieved from the files and rescreened for the presence of ES, granulomas and AFB. Presences of ES were correlated with AFB. STATISTICAL ANALYSIS: Stastistical analysis was done using Chi-square test. RESULTS: Our study included 103 cases. The common age group involved was 21-40 years, with female predominance. Cervical lymph nodes were most commonly involved. In relation to ES and AFB, four different cytological pictures were seen i.e., ES and AFB-(31%); ES-AFB+(16.5%); ES+, AFB+(39%); ES+AFB-(14.5%). Chi square test showed a highly significant stastistical association between ES and AFB with p=0.001. CONCLUSION: Eosinophilic structure is one of the cytomorphological features to be considered in necrotic lymph node aspirate which has a significant correlation with AFB in the smears. Hence pathologist should search for this, and it should be included in routine cytology reporting of tuberculosis lymphadenitis. PMID- 26816896 TI - Ultrasonography Guided Fine Needle Aspiration Cytology with Preparation of Cell Blocks in the Diagnosis of Intra- Abdominal Masses. AB - BACKGROUND: Ultrasonography guided Fine Needle Aspiration Cytology (FNAC) is currently the most favoured and increasingly used pre-operative diagnostic procedure in various deep seated neoplastic and non-neoplastic mass lesions. Cell blocks prepared from residual fine needle aspiration (FNA) material can aid in better morphologic assessment and contribute to establish a more definitive cytopathologic diagnosis. AIM: To assess the value of ultrasonography guided FNAC in the diagnosis of intra-abdominal (non-pelvic) masses. OBJECTIVES: To determine the reliability of ultrasonography guided FNAC in distinguishing neoplastic from non-neoplastic intra-abdominal mass lesions. To assess the usefulness of cell block as a complimentary diagnostic material in the morphologic evaluation of the lesions. MATERIALS AND METHODS: Aspirate material was collected from 62 patients with clinically and/or radiologically detected abdominal mass under ultrasonographic (USG) guidance. Pelvic masses were excluded from the study. In every case an attempt was made to prepare cell block (CB) from any residual material after preparation of routine smears. The final cytomorphologic diagnosis was correlated with clinical and radiologic findings, histopathologic diagnosis, follow up and response to therapy information. RESULTS: The diagnostic yield of USG guided FNAC was 96.77%. The cases included 42 malignant (67.74%), two (3.23%) benign, and 16 (25.8%) non-neoplastic lesions. Two (3.23%) smears were unsatisfactory for evaluation. In 45 out of 62 cases (72.58%) CB preparations were available. There was a good agreement between smear diagnosis and that observed on CB section. Additionally CB yielded better diagnostic material in 15.55% of cases and aided in establishing a more precise final cytopathologic diagnosis. Confirmation of diagnosis in the form of biopsy and/or surgically resected specimen and follow up was available in 56 cases. The overall diagnostic accuracy of USG guided FNAC was 96.43% with a sensitivity, specificity, positive predictive value and negative predictive value of 95.35%, 100%, 100% and 86.66% respectively. CONCLUSION: USG guided FNA procedure provides a good diagnostic yield for intra-abdominal masses. Also it has high sensitivity and specificity in differentiating benign from malignant lesions. Cell block preparations facilitate better diagnosis of lesions when reviewed along with cytological smears. PMID- 26816897 TI - Architectural Analysis of Picrosirius Red Stained Collagen in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma using Polarization Microscopy. AB - INTRODUCTION: Collagen degradation is important both for carcinogenesis and in its progression. Research regarding the co-relation of collagen with Oral Epithelial Dysplasia (OED) and Oral Squamous Cell Carcinoma (OSCC) is less explored. AIM: To elucidate the nature of collagen in Oral Epithelial Dysplasia (OED) and Oral Squamous Cell Carcinoma (OSCC) using Picrosirius Red Stain (PSR) under polarizing microscopy. MATERIALS AND METHODS: The study consisted of a total 40 samples which were divided into three groups. Group I included buccal mucosa as negative and irritation fibroma as positive control, group II consisted of OED and group III consisted of Oral Squamous Cell Carcinoma (OSCC). A histochemical analysis was conducted using PSR-polarization method by two independent observers. RESULTS: The control group shows predominantly reddish orange birefringence. In OED with the advancement of grades, the colour changed from yellowish-orange colour to yellow-greenish with progressive increase in greenish hue. As OSCC regresses from well to poorly differentiated, the colour changed from reddish-orange to yellowish orange to greenish-yellow suggesting a transition from mature to immature collagen. CONCLUSION: An observable gradual change in collagen of both OED and OSCC was noted as they were proceeding from benign to critical step. Thus, PSR is a useful tool for studying stromal changes as supporting collagen shows the transition in the form besides the alterations in epithelial cells. PMID- 26816898 TI - To Establish Bethesda System for Diagnosis of Thyroid Nodules on the Basis of Fnac with Histopathological Correlation. AB - INTRODUCTION: In October 2007, "The National Cancer Institute (NCI), Thyroid Fine Needle Aspiration State of the Science Conference" was held in Bethesda, Maryland hosted by the NCI with the intention of formulating internationally acceptable guidelines for reporting of thyroid cytopathology. This was because, thyroid FNAC have a reporting confusion due to multiplicity of category terminologies. To overcome this, The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was introduced for unifying the terminology and morphologic criteria along with the corresponding risk of malignancy. The Bethesda system for reporting thyroid cytopathology represents a major step towards standardization, reproducibility, improved clinical significance, and greater predictive value of thyroid fine needle aspirates (FNAs). AIM: The aim of this study was to elucidate the diagnostic utility of the Bethesda system in reporting thyroid FNAs and to assess the effectiveness of FNAC in the evaluation of thyroid nodules by comparing the results with histopathological evaluation. MATERIALS AND METHODS: The present study was carried out in our institute during the July 2012 to September 2014. In this study, 100 FNACs done which were classified according to the Bethesda system and out of them, 60 histopathological evaluations obtained from this group were evaluated. The sensitivity, specificity, positive and negative predictive values were evaluated. RESULTS: Out of 100 FNACs, 06% were Non-diagnostic, 78% were Benign, 04% were Atypical follicular lesion of undetermined significance (AFLUS), 04% were suspicious for Follicular neoplasm (SFN), 01% were suspicious for Follicular neoplasm Hurthle cell type, 03% were suspicious for malignancy (SM), and 04% malignant. In 60 cases, data of follow-up histopathologic examination (HPE) were available. The sensitivity was 88.89% and specificity was 84.31%. The positive and negative predictive value were 50% and 97.7%, respectively. CONCLUSION: The Bethesda system is very useful for a standardized system of reporting thyroid cytopathology, improving communication between cytopathologists and clinicians, and inter-laboratory agreement, leading to more consistent management approaches. An additional point which is in favor of the implementation of this system is that the classification is directly related to the risk of malignancy in each category, which in turn, prompts the recommended clinical management of that category, thus truly embodying the clinico pathological correlation in its true spirit. The correlation of FNAC with histopathology is necessary before starting treatment. PMID- 26816899 TI - Necrotizing Sialometaplasia of the Hard Palate: A Rare Entity of Dilemma on Cytology, Confirmatory on Histopathology. AB - Necrotizing sialometaplasia is a rare, benign reactive necrotizing lesion, involving sites where salivary gland tissue is usually present. The importance of this lesion is that it mimics malignancy clinically leading to treatments ranging from conservative excision to total maxillectomy. Cytologically and histologically also the lesion is often confused with neoplasms. We present a case of a lady with a hard palatal swelling, which was non - ulcerative unlike typical cases of necrotizing sialometaplsia. FNAC features made us strongly suspect a low grade mucoepidermiod carcinoma, following which the swelling was excised. Histopathology came to the rescue, on which the final diagnosis of necrotizing sialometaplasia of the hard palate was made. Necrotizing siaometaplasia is often misdiagnosed by the inexperienced cytologist, with histopathological examination being confirmatory. We also emphasize the fact that lesions like necrotizing sialometaplasia need a high degree of suspicion along with clinical co relation before subjecting the patient to unnecessary surgical procedures. PMID- 26816900 TI - Incidentally Detected Testicular Metastasis in a Case of Prostatic Adenocarcinoma. AB - Adenocarcinoma of the prostate is one of the common cancers among elderly men worldwide. However, testicular metastasis detected incidentally after orchiectomy is a rare presentation as most commonly we encounter patients presenting with bone metastasis at the time of primary diagnosis. Here, we describe a recently diagnosed case of prostatic carcinoma that had metastasis in a single testis, incidentally detected in the orchiectomy histopathological specimen, performed for surgical castration and emphasize the importance of routine microscopical examination of the testicular specimens. PMID- 26816901 TI - Disseminated Histoplasmosis in an Immunocompetent Patient Diagnosed on Bone Marrow Aspirate - A Rare Presentation from a Non-Endemic Area. AB - Histoplasmosis causing systemic fungal infection is commonly seen in endemic areas. In India, disease prevalence is more in eastern part of the country and there have been very few reports from southern part of India. The occurrence of disseminated histoplasmosis in immunocompetent individual is rare. We report a case of disseminated histoplasmosis in an immunocompetent individual with no underlying risk factors. The disease was not suspected clinically and was diagnosed by bone marrow aspirate incidentally. PMID- 26816902 TI - Primary Extra-Gonadal Retroperitoneal Seminoma, Clinically Mimicking Sarcoma. AB - Extra-gonadal Germ cell tumours (EGCTs) are germ cell tumours that are found in locations other than the gonads. These tumours are seen in young males in the midline, mostly in the mediastinum followed by retroperitoneum, pineal gland, and sacrococcygeal area. While most of these are non-seminomatous, few are seminomatous. We present here a case report of a 25-year-old, mentally retarded male patient, with bilaterally normal testes, who presented with a huge mass in abdomen. The ultrasound and CECT (Contrast Enhanced Computerized Tomography) scan done showed two large retroperitoneal masses, which on FNAC (Fine Needle Aspiration Cytology) suggested germ cell tumour. Surgical resection was done and the subsequent histopathological examination provided the diagnosis of seminoma, which was further confirmed by PAS (Periodic Acid Schiff) staining and Immunohistochemistry for PLAP (Placental Alkaline Phosphatase). Retroperitoneum is a common site for sarcomas, which also present as huge, bulky masses. Thus, EGCTs should be considered in the differential diagnosis of a soft-tissue mass in abdomen, especially arising in the retroperitoneum. PMID- 26816903 TI - Accelerated Phase of Chediak-Higashi Syndrome at Initial Presentation: A Case Report of an Uncommon Occurrence in a Rare Disorder. AB - Chediak-Higashi syndrome (CHS) is an uncommon and fatal congenital disorder. The characteristic features of CHS are partial oculocutaneous albinism, increased vulnerability to infections, presence of abnormal large granules in leukocytes and an accelerated lymphohistiocytic phase. Accelerated phase at initial presentation is rarely seen as it is usually preceded by repeated episodes of infections. Hence this interesting case of a four-month-old Indian child born to consanguineous parents in accelerated phase at initial presentation is described. The boy presented with fever, hepatosplenomegaly, and cleft lip. Clinical diagnosis was leukemia or a lysosomal storage disorder. Cytopaenias, lymphohistiocytic infiltration in bone marrow, and the characteristic large granules in leucocytes helped in the diagnosis, emphasizing the importance of bone marrow in diagnosis of unusual presentation of this rare disorder. PMID- 26816904 TI - Rare Co-existence of Squamous Cell Carcinoma with Infiltration of Renal Vein and Xanthogranulomatous Pyelonephritis. AB - Primary renal squamous cell carcinoma is a very rare malignancy of the upper urinary tract. Most patients have history of chronic urolithiasis, analgesics abuse, radiotherapy or infection. Co-existence of SCC with xanthogranulomatous pyelonephritis is exceedingly rare with only few reports in the literature. We report a case of a 60-year-old male presented with right flank pain and mild tenderness of abdomen. Computed tomography of the abdomen revealed gross hydronephrosis with parenchymal thinning and irregular thick enhancing wall of pelvicalyceal system with multiple calculi in right kidney. Right renal vein appeared distended, filled with hypo dense material. Right nephrectomy was performed and sent for pathological examination. Histological evaluation revealed keratinizing squamous cell carcinoma with infiltration of renal vein and xanthogranulomatous pyelonephritis. PMID- 26816905 TI - Fibroepithelial Polyp of the Tonsil: Report of a Rare Case. AB - Pedunculated polyps of the palatine tonsil are rare benign tumours of tonsil. Most of the cases have been reported in adults with varying presenting symptoms. We report a 12-year-old male child who presented with 6 months history of difficulty in swallowing. There was no history of breathing difficulty, change in voice or history of trauma. Clinical examination revealed a 2x1 cm small pedunculated polyp arising from the superior pole of right tonsil which was excised under general anaesthesia. Left tonsil was normal. A diagnosis of fibroepithelial polyp of right palatine tonsil was made based on histopathological findings. An unusual presentation of a rare condition in a paediatric patient has been discussed along with the clinical and histopathological features of this lesion. PMID- 26816906 TI - Giant Cell Tumour of Soft Tissue in Neck: An Uncommon Tumour in an Uncommon Location. AB - Giant cell tumour of soft tissue is an extremely rare tumour. It is thought to be the soft tissue counterpart of giant cell tumours of the bone due to its histological and immunohistochemical resemblances. Almost 80% of these tumours occur in upper and lower extremities; neck is a very rare location. Here we describe a case of primary soft tissue giant cell tumour in right submandibular region. A 35-year-old male patient presented with a swelling in right submandibular area. FNAC suggested a benign soft tissue neoplasm, comprising of spindle cells and multinucleated giant cells. Histopathology of resected specimen showed spindle cell tumour with intricately mixed giant cells, consistent with a primary giant cell tumour of soft tissue. Giant cells were CD 68 positive. Giant cell tumour of soft tissue is benign tumour, though very rarely can show features of malignancy. We present this case for its rarity and morphological overlap with other soft tissue neoplasms containing giant cells. PMID- 26816908 TI - Atypical Fibroxanthoma of Scalp: A Paradoxical Benign Tumour. PMID- 26816907 TI - Malignant Melanoma of Nasal Cavity- A Case Report. AB - Malignant Melanoma of nasal cavity is an extremely rare tumour and is more aggressive than its cutaneous counterpart. Primary malignant melanoma of nasal cavity arise from melanocytes located in the mucous membrane. Only 0.5% of malignant melanoma arises in nasal cavity. We report a case of malignant melanoma of the nasal cavity in a 51-year-old male who presented with swelling of nose, nasal block and epistaxis. By brush cytology and CT scan imaging, the pre operative diagnosis of malignant melanoma was made which was later confirmed by histopathology examination along with immunohistochemistry by using S100 and HMB 45. Malignant melanoma of nose is rare tumour, with aggressive behavior and poor prognosis. Rarity of this lesion warrants its mention and emphasizes the importance of considering malignant melanoma among the differential diagnosis of tumours of nose and paranasal sinuses. PMID- 26816910 TI - Evaluation of Skin Penetration of Diclofenac from a Novel Topical Non Aqueous Solution: A Comparative Bioavailability Study. AB - INTRODUCTION: Different topical formulations of diclofenac have varying skin penetration profile. Recent advances in science and technology has led to the development of many new formulations of drugs for topical drug delivery. One such technological development has led to the innovation of Dynapar QPS, a novel, non aqueous, quick penetrating solution (QPS) of diclofenac diethylamine. AIM: This study was aimed to measure the total exposure from the drug penetrating the skin in healthy human subjects and comparing the relative systemic bioavailability of Dynapar QPS((r)) with diclofenac emulgel. MATERIALS AND METHODS: A 200 mg of diclofenac from either Dynapar QPS((r)) (5 ml) or emulgel (20 g) was applied on back of subject as per the randomisation schedule. Blood samples were collected up to 16 hours post drug application. Plasma concentration of diclofenac was measured by pre-validated HPLC method. Pharmacokinetic (PK) parameters like Cmax, Tmax, t1/2, AUC0-t, AUC0-infinity, and Kel, of diclofenac were determined for both the formulations. RESULTS: Mean Cmax after administration of Dynapar QPS((r)) and diclofenac emulgel were 175.93 and 40.04 ng/ml, respectively. Tmax of diclofenac was almost half with QPS compared to emulgel (5.24 hrs versus 9.53 hrs respectively). The mean AUC0-t and AUC0-infinity after administration of Dynapar QPS((r)) was higher as compared to diclofenac emulgel (AUC0-t: 1224.19 versus 289.78 ng.h/ml, respectively; AUC0-infinity: 1718.21 versus 513.83 ng.h/ml, respectively). None of the subject experienced any adverse event during the study. CONCLUSION: The results indicate an enhanced penetration and subsequent absorption of diclofenac from Dynapar QPS((r)) as compared to diclofenac emulgel. Higher penetration is likely to translate into better pain relief in patients. PMID- 26816909 TI - Efficacy, Safety and Treatment Satisfaction of Glimepiride vs Sitagliptin in Combination with Metformin in Type 2 Diabetes Mellitus. AB - INTRODUCTION: Metformin is a preferred drug for starting treatment in type 2 diabetes mellitus. But, eventually most of the patients need additional drug to control blood sugar level. The choice of drug depends upon several factors including patient specific criteria, economical factors and treatment satisfaction. AIM: The aim of the present study is to investigate the effects of adding sitagliptin or glimepiride on efficacy, safety and treatment satisfaction in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: It was a retrospective observational study on 50 patients each in sitagliptin and glimepiride group, who are receiving treatment for at least 12 weeks and are stable on respective treatment regimen. Glycated haemoglobin (HBA1c) was the primary measure of efficacy. Safety was assessed by checking weight gain/loss, hypoglycaemia episodes and other laboratory investigations. Patient satisfaction was assessed by Diabetes Treatment Satisfaction Questionnaire. RESULTS: The HbA1c level after 12-24 weeks of treatment was not found to be significant compared to each other or from baseline. Compared to baseline fasting plasma glucose & postprandial plasma glucose were lower in glimepiride group. Sitagliptin was associated with less episodes of hypoglycaemia. Weight gain was associated with glimepiride but it was non-significant (p=0.08). Overall treatment satisfaction score were better for sitagliptin but were not statistically significant. CONCLUSION: The efficacy of sitagliptin was comparable. Sitagliptin had superior adverse effect profile with less chances of hypoglycaemia and weight gain. Questionnaire scores were higher for sitagliptin indicating better treatment satisfaction compared to glimepiride. PMID- 26816911 TI - Evaluation of Anti Cancer Effects of DPP-4 Inhibitors in Colon Cancer- An Invitro Study. AB - INTRODUCTION: Among the oral anti-diabetic drugs, Dipeptidyl peptidase - 4(DPP-4) inhibitor is an emerging class of drugs. Inhibitors of DPP-4 enzyme like Sitagliptin and Vildagliptin have shown Anti-oxidant properties in many studies, both invivo and invitro. It has also been characterized as an apoptotic agent on pancreatic cancer cells. In the following study, Anticancer effect of DPP 4 inhibitors on colon cell lines (HT-29) using MTT assay- {3 -4, 5-dimethyl (thiazol - 2 -yl) -3, 5- dimethyl tetrazolium bromide} assay was elucidated. AIM: To elucidate and compare the anticancer potential of two DPP 4 inhibitors using in-vitro MTT assay on colorectal cell lines (HT-29). MATERIALS AND METHODS: We treated HT-29 cell lines with two DPP 4 inhibitors. HT-29 cells were incubated at 37(0)C and drug samples were added in various concentrations and incubated for 24 hours. MTT dye was added to the sample and it was incubated for 4 hours. One ml of DMSO was added Using an Ultraviolet-Spectrophotometer, measurement of absorbance was done at 570nm following which the half maximal inhibitory concentration was graphically estimated in relation to the percentage of viability of the cell and the sample concentration. RESULTS: We found that both the drugs have shown anticancer activity starting from low to high concentrations when compared with the control using MTT assay. The IC 50 value of Sitagliptin is 31.2 mcg/ml and Vildagliptin is 125 mcg/ml. CONCLUSION: From this study, we found that the drugs have significant Anti-Cancer property, which would probably play a role as cytotoxic agent in tumour cells. Sitagliptin was found to be more potent than Vildagliptin in colon cancer cell lines. PMID- 26816913 TI - Metronidazole-Induced Bullous Pemphigoid: A Case Report. AB - Bullous pemphigoid is an autoimmune cutaneous blistering disorder, the exact pathogenesis of which is still not fully elucidated. Drug-induced bullous pemphigoid eruptions are rare but have been reported earlier with the use of frusemide, psoralens, ibuprofen, galantamine hydrobromide, ACE inhibitors like captopril, spironolactone, penicillin, ampicillin, levofloxacin, penicillamine. We hereby report a case of metronidazole induced bullous pemphigoid (BP) in a 52 year-old male patient suffering from liver abscess following 4 days of drug administration. The skin biopsy findings obtained from the patient were consistent with the diagnosis of bullous pemphigoid (BP). Metronidazole was discontinued and symptomatic treatment was offered to the patient. Following withdrawal of metronidazole, the bullae subsided in the next 7-10 days without any significant residual scarring. The causality assessment performed as per the Naranjo algorithm revealed the case to be probable (Naranjo score 7). PMID- 26816912 TI - Knowledge, Attitude and Practice of Self-Medication Among Basic Science Undergraduate Medical Students in a Medical School in Western Nepal. AB - INTRODUCTION: Studies have shown self-medication to be common among medical students. These studies are however, few in Nepal. The present study assessed knowledge, attitude, and practice of self-medication among second and fourth semesters' undergraduate medical students and studied differences in knowledge and attitude (if any) among different subgroups of the respondents. MATERIALS AND METHODS: A cross-sectional survey was conducted using a questionnaire among basic science medical students of Manipal College of Medical Sciences, Nepal. Semester of study, gender, age, nationality, and the profession of their parents were noted. Students' knowledge and attitude about self-medication was studied by noting their degree of agreement with a set of 40 statements using a Likert-type scale. The average scores and frequency of occurrence of particular behaviors among different categories of respondents were compared using appropriate statistical tests. RESULTS: Two hundred and seventy-six of the 295 (93.6%) students participated. The mean (SD) knowledge, attitude, and total scores were 74.54 (6.92), 67.18 (5.68), and 141.73 (10.76) with maximum possible scores 100, 100 and 200, respectively. There was no significant difference in scores according to respondents' gender, age, and the profession of their parents. However, the mean knowledge, attitude and total scores were significantly different among students of different nationalities. Mean scores of fourth semester students were significantly higher compared to second semester students. There were differences in knowledge and total scores among students of different nationalities. Eighty two percent of respondents had self-medicated during the one year period preceding the study; 149 respondents (54%) shared that previous experience with the medicine was one of the information sources for self medication. Prevalence of self-medication among respondents according to semester of study, gender, age, and profession of the parents was not significantly different. The use of self-medication was more common among Sri Lankan respondents compared to Nepalese. Painkillers (73.2%), antipyretics (68.8%), and antimicrobials (56.2%) were most commonly used for self-medication. CONCLUSION: Students' knowledge and attitude about self-medication is good. The prevalence of self-medication among medical students was high. PMID- 26816914 TI - Effects of Pomegranate Seed Oil on the Fertilization Potency of Rat's Sperm. AB - BACKGROUND: Pomegranate has been taken great scientific attention in recent years due to its health benefits. Pomegranate seed oil is a rich source of 9-cis, and 11-trans conjugate linolenic acid. The aim of this study was to evaluate the effect of dietary pomegranate seed oil on the fertilization potency of rat's sperm. MATERIALS AND METHODS: Twenty-four male Wistar rats were divided into four groups. The first group, which served as the control group, received 1 mL of corn oil for seven weeks. Groups II, III, IV served as the experimental groups received 200, 500 and 1000 mg/kg of pomegranate seed oil, for the same period of time respectively. After seven weeks, all of the rats were sacrificed, and their epididymis sperm was collected and added to IVF medium (T6) containing metaphase II oocytes. Almost 21 oocytes had been removed from every female rat oviduct. In this medium, oocyte fertilization, cleavage rates, and embryo development into blastocysts, were evaluated by inverted microscopy. RESULTS: Levels of LD50 in the oral route in male rats were more than 5000 mg/kg body weight. Our data showed that the rates of fertilization, cleavage and embryo development into blastocysts were higher in the groups that had received 500 and 1000 mg/kg body weight of pomegranate seed oil. CONCLUSION: This study demonstrated that pomegranate seed oil had a positive effect on the fertilization potency of male rats. These beneficial effects may be useful in assisted reproductive technology. PMID- 26816915 TI - The Induction of Oxidative/Nitrosative Stress, Inflammation, and Apoptosis by a Ferric Carboxymaltose Copy Compared to Iron Sucrose in a Non-Clinical Model. AB - INTRODUCTION: Ferric carboxymaltose is a next-generation polynuclear iron(III) hydroxide carbohydrate complex for intravenous iron therapy belonging to the class of so-called non-biological complex drugs. The product characteristics and therapeutic performance of non-biological complex drugs are largely defined by the manufacturing process. A follow-on product, termed herein as ferric carboxymaltose similar, is available in India. Given that non-biological complex drugs may display differences in diverse product properties not characterisable by physico-chemical methods alone. AIM: The aim is to assess the effects of this ferric carboxymaltose similar in our non-clinical model in non-anaemic healthy rats. MATERIALS AND METHODS: Non-anaemic rats were treated with intravenous ferric carboxymaltose similar or iron sucrose both at (40 mg iron/kg body weight), or with saline solution (control) for four weeks, after which the animals were sacrificed. Parameters for tissue iron distribution, oxidative stress, nitrosative stress, inflammation and apoptosis were assessed by immunohistomorphometry. RESULTS: Ferric carboxymaltose similar resulted in deranged iron distribution versus iron sucrose originator as indicated by increased serum iron, transferrin saturation and tissue iron(III) deposits as well as decreased ferritin deposits in the liver, heart and kidneys versus iron sucrose originator. Ferric carboxymaltose similar also increased significantly oxidative/nitrosative stress, pro-inflammatory, and apoptosis markers in the liver, heart and kidneys versus iron sucrose originator. CONCLUSION: In our rat model, ferric carboxymaltose similar had a less favourable safety profile than iron sucrose originator, adversely affecting iron deposition, oxidative and nitrosative stress, inflammatory responses, with impaired liver and kidney function. PMID- 26816916 TI - Valproate Induced Hyperammonemic Delirium. AB - Sodium valproate induced hyperammonaemic delirium with normal liver function tests is a relatively uncommon adverse effect. It may be mistaken for psychosis or worsening of mania leading to wrong diagnosis and improper management. Plasma ammonia levels should be monitored in all patients developing altered mental status after receiving valproate therapy. This is a case series of hyperammonaemic delirium due to valproate reported to the Department of Pharmacology from Department of Psychiatry over a period of one year. PMID- 26816917 TI - Study of Pattern of Change in Handwriting Class Characters with Different Grades of Myopia. AB - INTRODUCTION: Handwriting is a visuo-motor skill highly dependent on visual skills. Any defect in the visual inputs could affect a change in the handwriting. Understanding the variation in handwriting characters caused by visual acuity change can help in identifying learning disabilities in children and also assess the disability in elderly. In our study we try to analyse and catalogue these changes in the handwriting of a person. MATERIALS AND METHODS: The study was conducted among 100 subjects having normal visual acuity. They were asked to perform a set of writing tasks, after which the same tasks were repeated after inducing different grades of myopia. Changes in the handwriting class characters were analysed and compared in all grades of myopia. RESULTS: In the study it was found that the letter size, pastiosity, word omissions, inability to stay on line all increase with changes in visual acuity. However these finding are not proportional to the grade of myopia. CONCLUSION: From the findings of the study it can be concluded that myopia significantly influences the handwriting and any change in visual acuity would induce corresponding changes in handwriting. There is increase in letter size, pastiosity where as the ability to stay on line and space between the lines decrease in different grades of myopia. The changes are not linear and cannot be used to predict the grade of myopia but can be used as parameters suggestive of refractive error. PMID- 26816918 TI - Perception of Medical Students about Communication Skills Laboratory (CSL) in a Rural Medical College of Central India. AB - INTRODUCTION: "The art of medicine is intricately tied to the art of communication." In traditional medical curriculum, communication is not taught formally and this leads to a gap in reliability and consistency of the teaching. Few studies have shown that much litigation against doctors is due to lack of communication and not because of lack of clinical expertise. Considering the importance of training in communication skills, it was included in the curriculum of students of DMIMS (DU), which has got probably the first communication skills lab in a medical college in India. AIM: To study the perception of medical students about usefulness of communication skills lab. MATERIALS AND METHODS: This observational study was carried out at Communication Skills Lab (CSL) of Jawaharlal Nehru Medical College, Sawangi (M), Wardha, Maharasthra. Feedback was obtained with the help of a prevalidated questionnaire from 65 final MBBS students about their perception about utility of the module taught in the CSL including factors which helped and which hindered in learning. Descriptive statistics was used for the quantitative data and categorization for qualitative data. RESULTS: A total of 78.46% students were of the idea that CSL posting is must for all medical undergraduates. A 93.83% perceive that the module taught was very relevant and useful and were satisfied with the duration of posting (81.47%). A 78.46% students experienced improvement in their communication skills. They opined that more emphasis should be given on communication between doctor and patient (61.53%). CONCLUSION: The students found communication skills lab very useful. They desired more emphasis on communication between doctor and patient and sought more interactivity, video demonstrations to be part of the module. PMID- 26816919 TI - The Knowledge of Radiation and the Attitude Towards Radio-Protection among Urology Residents in India. AB - INTRODUCTION: Exposure to radiation is a hazard and precautions are necessary to limit it. This study was done to assess the knowledge of radiation and the attitude towards radio-protection among urology residents in India. MATERIALS AND METHODS: A questionnaire was administered to assess the knowledge and attitude of urology residents who came from all over the country to attend a clinical meeting at Apollo Gleneagles Hospital, Kolkata, India. RESULTS: All the respondents agreed to being exposed to radiation, with 78.2% using radiation in more than five cases a week. Only 65.2% always took some steps for radio-protection. Lead aprons and thyroid shields were the most common radiation protection devices used. None of the residents ever used lead gloves or protective eye glasses or dosimeters. An 82.6% felt that they did not have adequate knowledge, 85.4% of residents did not receive any formal classes regarding the risk of radiation, 21.7% either rarely or never moved out of the operating room when the radiation was being used, 42.4% did not know that the SI unit of the equivalent absorbed dose of radiation & 52.1% did not know about the amount of radiation delivered to an adult during a contrast enhanced CT scan of the abdomen. CONCLUSION: Results of the present study reveal that the urology residents of India lack knowledge about the risks of radiation exposure. Majority of them did not take necessary precautions to limit their exposure to radiation. PMID- 26816920 TI - Disaster Management and the Role of Oral Maxillofacial Surgeons. AB - "Disaster" the word itself suggests an event resulting in great loss and misfortune. In this developing world, India is becoming more powerful and is shining across the world. But we are still left to deal with various disasters, so that no harm comes to mankind. India has the occasional national disaster to which we have to promptly respond. Like the rest of the world, India has become a terror prone nation and recent attacks since the last decades affected not only the function but also it made citizens insecure. As we are in a large nation so, no matter how large a disaster it may be; we have to overcome it. The oral and maxillofacial region in a human body is very delicate with complicated anatomy, which decides the life of a human being. The management of disaster is a multitask approach, in which maxillofacial surgeon plays an important role. It is a very difficult task to operate in disaster zone. It is essential for a surgeon to make quick and important decisions under stressful conditions. Usually the surgeries are performed in a well-equipped hospital but, when it comes to disaster zone the surgeon have to treat the patient with a minimal armamentarium available within a fraction of time. The surgical competence in a disaster field is an alarming situation. Disaster management itself is not an alarming situation but the time management is important for better outcomes. A surgeon however should be trained, so that he should not miss injuries for better outcomes along with personal safety. The article discusses about disaster management strategy and guidelines for both oral maxillofacial surgeons and the statuary body to make maxillofacial surgeon as part of disaster management team for better outcomes. PMID- 26816921 TI - A Three-year (2011-2013) Surveillance on Animal Bites and Victims Vaccination in the South of Khorasan-e-Razavi Province, Iran. AB - INTRODUCTION: Rabies is acute encephalitis caused by rabies virus and is transmissible between humans and warm blooded animals. The virus is belong to the family of Rabdoviridae and, of Lissavirus genus. AIM: To find out the success of rabies surveillance system to prevent victims of this deadly disease and to identify its risk factors in the community. MATERIALS AND METHODS: This research is a cross-sectional analysis and the information pertaining to bite incidents was obtained from documents of the Centers for Disease Control of Rabies from 2011 to 2013. A questionnaire was used which included questions on demographics information (sex and age) of the victims, and the others. RESULTS: A total of 616 cases (animal rabies) were brought to rabies treatment center during 2011- 2013 of which 81.2% of the cases were males and 18.8% were females. Most animal bites (37.5%) reported in 2011. The difference between the months and the number of biting were statistically significant (p = 0.001). Animal biting was more frequent among people of age group 21-30 years than other age groups which constituted roughly 27.2% of the cases. There was no significant relationship between the variables of gender and site of the bites victims, (p> 0.05). Domestic dog bite was most frequent, found in 66.7% cases. 83.9% victims had been uncompleted vaccinated and 16.1% were completed. CONCLUSION: Since, the cost of conservation was high for the health system after biting, preventive programs should be concentrated on public health instructions, particularly in villagers, free occupation and emphasis to ranchers that have collar dogs during the day. PMID- 26816922 TI - Knowledge, Attitude and Practice of Ear Care in Coastal Karnataka. AB - INTRODUCTION: Ear as an organ is necessary for the perception of sound and body balance. Ear infection, diabetes mellitus, hypertension and excessive use of mobile phone for listening to music at high volume all can reduce hearing. No earlier study was available in the costal Karnataka population, regarding the practice of ear care. The study objective was to ascertain the level of knowledge of the community regarding ear care, to find out whether some of the common conditions affecting hearing are known and to find out the common practices involved in maintaining ear hygiene. MATERIALS AND METHODS: This cross-sectional study was conducted on 500 subjects in two tertiary care hospitals by convenient sampling, using self-administered questionnaire. Knowledge, Attitude and Practice across the age groups, religion & education background were studied. RESULTS: Across different education groups, 66.7%-90% did not know that 'cold' can cause ear infection and 46.7%-75.0% did not know that diabetes and hypertension can reduce hearing. When there is ear pain or discharge, people put ear drops available at home in 48.3%-75.0% across 3 age groups; 58.5%-61.5% across 3 religions and 44.8%-67.9% across 5 education groups. No statistically significant difference was found in the practice of pouring oil into ears across religions. A total of 58.6%-100% daily clean inside the ear and 70-100% use cotton buds. CONCLUSION: General perception of the people is that ear is necessary only for hearing. Majority did not know that nasal infection can affect the ear and that DM and hypertension can cause hearing loss. When there is ear pain and discharge, most of the adults put drops that are available at home. Pouring oil into the ears and cleaning inside the ear canals is routinely practiced in costal Karnataka. PMID- 26816923 TI - Intrathyroid Injection of Steroid in Benign Thyroid Swellings. AB - INTRODUCTION: Benign thyroid swelling disorders are common conditions, frequently encountered in clinical practice. Though medical management has been useful in treating the hormonal variations, it has not been very significant in reducing the size of the swelling. OBJECTIVE: To study the efficacy of intra thyroid injection of triamcinolone in benign thyroid swelling disorders. MATERIALS AND METHODS: A total of 20 patients were selected for this study. All the patients with thyroid swellings, were evaluated with history and clinical examination followed by routine blood investigations, thyroid function tests (T3,T4,TSH), Fine Needle Aspiration Cytology (FNAC) and Ultrasonography (USG) of the neck. The treatment adopted in this study was intrathyroid injection of triamcinolone acetonide. RESULTS: In this study there were 20 patients, all were females in the age group of 17- 55 years. Four patients did not come for regular follow up, and hence were excluded. Sixteen patients were followed up regularly. Thirteen (81.25 %) patients showed excellent results with no visible swelling, confirmed sonologically. Two patients (12.5%) showed fair results with residual swellings, and one patient did not show any reduction in size of the swelling. CONCLUSION: Intrathyroid injection of triamcinolone acetonide is a safe, minimally invasive technique in reducing the size of benign thyroid swellings with minimal or no side effects. PMID- 26816924 TI - Difficulties in Management of a Sessile Subglottic Polyp. AB - Benign laryngeal polyps are usually managed with micro-laryngeal surgery. Occasionally surgery becomes challenging because of size of the polyp or its location. Maintaining the anaesthesia and the airway becomes difficult either during immediate management or during excision. Upper airway obstruction still remains the major indication for tracheostomy in many centers. Nowadays Laryngeal tumour has become the main indication of tracheostomy. Conditions like infections, trauma, benign lesions and prolonged intubation were leading indications previously. Otolaryngologist has to decide a method, often on the spot. Here we are presenting such a case where emergency tracheostomy was the only choice. PMID- 26816925 TI - Nasal Septal Angiofibroma in a Post-Menopausal Woman: A Rare Entity. AB - Juvenile angiofibromas (JAs) are well-characterised in literature, arising typically in the posterolateral wall of the nasal cavity of young males. Numerous theories have been proposed to explain the occurrence of this unique and rare tumour. Angiofibromas originating in other sites within the head and neck have been described but this is exceedingly rare, constituting less than 2% of all diagnosed cases. Extranasopharyngeal angiofibroma is a rare lesion, and more importantly, controversial. It is not known whether it is actually a relative of the well-known JA that is seen exclusively in adolescent males. We present the case of a post-menopausal woman with unilateral nasal obstruction who was unexpectedly diagnosed as nasal septal angiofibroma. PMID- 26816926 TI - Primary Cavernous Haemangioma of the Frontal Bone: Computed Tomography Features. PMID- 26816927 TI - Glaucoma Awareness and Self-Care Practices among the Health Professionals in a Medical College Hospital. AB - BACKGROUND: Awareness and self-care practices concerning glaucoma, the silent thief of sight, is poor. This study was conducted to assess the same among health professionals in a medical college. MATERIALS AND METHODS: Institutional Ethics Committee Clearance was obtained and a descriptive semi-structured-questionnaire based study was conducted. Informed written consent was taken from 114 (convenience sampling) health professionals (doctors/paramedicals) and a questionnaire were administered. Participants were questioned about the awareness of glaucoma, what are the features of glaucoma etc. Non-medical hospital workers were excluded. Data was analysed using Microsoft excel, descriptive statistics and chi-square test. RESULTS: Respondents included clinicians, non-clinician doctors and paramedicals (36:30:48) {mean age: 37 years, males:females::58:56}. Glaucoma awareness was statistically similar in the three study groups: high IOP (82.4%, p=0.55); optic nerve damage (32.4%, p=0.79); normal/low IOP (38.6%, p=0.2); irreversible blindness (47.1%, p=0.29); risk factors like corticosteroids (57%, p=0.11), family history of glaucoma (74.5%, p=0.17) and diabetes (77.1%, p=0.84). Over 13% thought that screening is done after 60 years. Few had undertaken screening for themselves (16.60%) and family members (21.05%). Few knew tests (41.2%, p=0.04) and treatment modalities (41.2%, p=0.0516). CONCLUSION: The study revealed unsatisfactory awareness and self-care practices concerning glaucoma among health professionals including clinicians despite studying ophthalmology, although it is presumed and predicted to be the contrary. This alarming revelation warrants the need for enrichment of glaucoma awareness programs. PMID- 26816928 TI - Outcome of Capsular Tension Ring (CTR) Implant in Complicated Cataracts. AB - INTRODUCTION: Surgery in the presence of zonular weakness or subluxated lens was a great surgical challenge and included intracapsular cataract extraction with anterior chamber IOL implantation or pars plana lensectomy and vitrectomy with a sutured (IOL). Modern surgical approache involves placement of endocapsular flexible PMMA ring that prevents iatrogenic loss of zonular support, minimizing vitreous loss and enables placement of in the bag IOL. AIM: To evaluate frequency and indications of capsular tension ring (CTR) implant and analyse the visual and anatomical outcome in various complicated cataract surgeries. MATERIALS AND METHODS: Retrospective screening of database of 6000 consecutive cataract surgeries was done. BCVA, complete ocular examination with SLEx, intraocular pressure, direct ophthalmoscope, fundus examination with +78/+90D were noted. CTR was implanted in cases where Zonular dialysis of > 3 clock hours was present or capsular bag instability was detected during capsulorhexis or subsequent intraoperative maneuvers. In cases with capsulorrhexis extension, CTR was not implanted. Records were analysed for indication of CTR implant and clinical outcome on Day 1, 1 month and 6 month follow up. RESULTS: In this series CTR implant was done in 45 cases. The indications were hypermature senile cataract in 9 cases, hypermature senile cataract with lens induced glaucoma in 9 cases, pseudoexfoliation syndrome in 9 cases, post blunt injury traumatic cataract in 6 cases, iridochoroidal coloboma in 6 cases, hypermature cataract with pseudoexfoliation and marfan syndrome in 3 cases respectively. Decision of CTR implant was intraoperative in 42 patients. At 6 month follow up, 39 patients had best corrected visual acuity >=6/12. IOL decentration was detected in only 3 cases, but without any subjective visual complaints. CONCLUSION: As per the results CTR was used very infrequently (0.75%) but remains useful in cataract surgeries with difficult pre and intraoperative conditions. It gives good postoperative result and creates satisfied patients. PMID- 26816929 TI - Opportunistic Screening of Vitamin B12 Deficiency in IT Professionals Presenting for Routine Health Check-up. AB - INTRODUCTION: Vitamin B12 deficiency is mainly diagnosed in symptomatic patients. However, the deficiency may also be prevalent in asymptomatic patients. Our aim was to study the prevalence of Vit B12 deficiency in IT professionals (Information Technology Professionals from Software industry) who presented for routine health screening and to correlate the deficiency to various parameters. MATERIALS AND METHODS: This was single centre, observational study comprising of 84 IT professionals. The data was collected in structured format. The study was designed to identify prevalence of Vit B12 deficiency and correlate to other factors such as type of diet, income level & regular use of medication (such as Antacid & Metformin). RESULTS: Total 28 individuals were found to be deficient (33.34%). Prevalence of Vit B12 deficiency amongst Vegetarian and non vegetarian diet adhering subjects was 47.5% and 20.45% respectively. B12 deficiency was also prevalent in high income age group. Further chronic intake of PPI (Proton pump inhibitor) and Metformin was associated with prevalence of 37.5% and 33.34% in the present study. CONCLUSION: During health screening of IT Professionals, significant prevalence of Vit B12 deficiency was noted across all income groups & non vegetarian diet consuming subjects also. There is significant correlation between Vit B12 deficiency with chronic use of PPI and Metformin. PMID- 26816930 TI - Evaluation of Coronary Artery Status by Coronary Angiography after First Survival of Acute Myocardial Infarction. AB - INTRODUCTION: Acute Myocardial Infarction (AMI) is a life threatening medical emergency which needs urgent medical attention. It is one of the major cause of mortality and morbidity throughout the world. AIM: The aim of the present study was to assess the coronary artery status by Coronary Angiography (CAG) after first survival of the Acute Myocardial Infarction (AMI) and to correlate the CAG findings with Coronary Artery Disease (CAD) Risk Factor (RF) and effect of early thrombolysis. MATERIALS AND METHODS: CAG was done on 870 patients consecutively from June 2013 to May 2015. Age, Gender, Body Mass Index (BMI), CAD risk factors (RF) such as Type 2 diabetes mellitus (T2 DM), hypertension, dyslipidaemia, smoking status and history of thrombolyctic status were recorded. The correlation between the CAD risk factors (RF) and the CAG findings were statistically analyzed. RESULTS: Coronary heart disease risk factors analysis revealed >= three RF in 23.88%, two RF in 29.88% and one RFin 45.86% of patients. CAG showed Single Vessel Disease (SVD) in 236 (27.1%) patients, double vessel disease (DVD) in 220(25.2%) patients, Triple Vessel Disease (TVD) in 252 (28.9%) patients. Multiple coronary artery involvement were found in the high risk group patients, which was found statistically significant (p-value<0.0001). A total of 348/870 (40%) patients were thrombolysed amongst them 80 (22.9%) revealed minimal and/or normal coronary artery which was found statistically significant (p value<0.0001). CONCLUSION: Higher the coronary risk factors, more the chance of the multiple coronary arteries involvement. All AMI patients should be thrombolysed as early as possible to get the benefit of recanalization of the culprit vessel. PMID- 26816932 TI - Study of Effectiveness and Safety of Percutaneous Balloon Mitral Valvulotomy for Treatment of Pregnant Patients with Severe Mitral Stenosis. AB - INTRODUCTION: In pregnant women mitral stenosis is the commonest cardiac valvular lesion. When it is present in majorly severe condition it leads to maternal and fetal morbidity and mortality. In mitral stenosis pregnancy can lead to development of heart failure. AIM: To evaluate the safety and efficacy of balloon mitral valvulotomy (BMV) in pregnant females with severe mitral stenosis. MATERIALS AND METHODS: A total of 30 pregnant patients who underwent BMV were included in the study from July 2011 to November 2013. Clinical follow-up during pregnancy was done every 3 months until delivery and after delivery. The mean follow up time after BMV was 6.72+/-0.56 months. RESULTS: From the 30 pregnant females 14 (46.67%) and 16 (53.3%) patients underwent BMV during the third and second trimester of pregnancy respectively. The mean mitral valve area was 0.85+0.16 cm(2) before BMV that increased to 1.60+0.27 cm(2) (p<0.0001) immediately after BMV. Peak and mean diastolic gradients had decreased significantly within 48 hours after the procedure (p<0.001) but remained very much unchanged at 6.72 month period of follow-up. Two patients had an increase in mitral regurgitation by 2 grades. CONCLUSION: During pregnancy BMV technique is safe and effective in patients with severe mitral stenosis. This results in marked symptomatic relief along with long term maternal and fetal outcomes. PMID- 26816931 TI - Evaluation of Endothelial and Platelet Derived Microparticles in Patients with Acute Coronary Syndrome. AB - BACKGROUND: Microparticles (MP) are a nuclear fragments of membrane released by the damaged cell during stress. Elevated levels of MP have been found in patients with acute coronary syndrome (ACS) owing to the damage in the endothelium. AIM: To determine if the levels of endothelial and platelet microparticles (EMP & PMP) in patients with ACS influenced the severity of the disease. MATERIALS AND METHODS: This was a prospective cohort study performed in 63 ACS patients (ST elevation myocardial infarction- STEMI-28, non ST elevation myocardial infarction -NSTEMI-35). After obtaining consent, blood samples were collected from the patients and processed by flow cytometry. RESULTS: The NSTEMI group had higher levels of EMP {792.11(327.59-1661.49) vs 300.35 (176.3-550.46), p=0.001} and PMP {218.87(86.65-439.77) vs 114.45(50.34-196.75), p= 0.007} as compared to the STEMI group. However, it was found that the EMP (r=-0.438, p=0.001) and PMP (r= -0.316, p=0.024) negatively correlated with Global Registry of Acute Coronary Events score (GRACE in-hospital score) for the entire cohort. CONCLUSION: The levels of microparticles are elevated in ACS patients and may reflect a protective effect in patients with acute coronary syndrome. PMID- 26816933 TI - Perceptions of Interns and General Medicine Examiners Regarding Cardiovascular Case Presentation in Practical Exams of General Medicine in Final MBBS Summative Examinations. AB - INTRODUCTION: Assessment of cardiovascular cases in practical exit exam is limited to simple history taking and physical examination. Standards of assessment are not uniform. This makes assessment less valid and reliable. AIM: To explore the perceptions of Internees and General Medicine Examiners about current practices in Cardio Vascular system (CVS) case presentation in final MBBS exit exams and the necessity to change some of the practices. MATERIALS AND METHODS: A set questions pertaining to the preparation for exams, validity, reliability, feasibility and educational impact were prepared to guide in obtaining the perceptions of internees and internal medicine examiners. Focus group discussions were conducted. Data Analysis was done by immersion crystallization process. RESULTS: Most of the internees admitted to feeling concerned because of difficulty in diagnosing murmurs by auscultation. Most of the examiners felt concerned about the logistics involved in arranging practical exams. Both admitted to the lack of uniform standards in assessment. Both agreed that the present system thrived as it was relatively feasible. Some internees suggested that the exam may be conducted in two parts by splitting the syllabus instead of once. Some internees suggested incorporating a student-doctor program to improve practical skills just like the on-going student nurse program. CONCLUSION: There is a need for overhauling the assessment of cardiovascular system in final MBBS summative exams towards one aligned to the competencies as required in an Indian Medical Graduate. Blueprinting of practical assessment with due weightage assigned to epidemiologically important topics is the need of the hour. PMID- 26816934 TI - The Diagnosis of Sigmoid Liposarcoma in a Young Male with Metabolic Syndrome. AB - The clinical picture and risk factors are decisive in differential diagnosis. It was proved that patients with metabolic syndrome have increased incidence of malignant tumours. The visceral adipose tissue releases active proteins that promote oncogenesis. We are presenting a case of 34-year-old male with metabolic syndrome suffering from pain in left iliac fossa with accompanying variable stool pattern. At first, the sigmoid diverticulosis was suspected. Patient's condition after the treatment has improved. The ambulatory, partial colonoscopy revealed a cauliflower-like, balloting, wide-base growth in the sigmoid that narrowed its lumen. The biopsy did not reveal atypical growth characteristics. Because of tumour type and enlarged regional lymph nodes seen in abdomen CT scan, the segmental colon resection and end-to-end anastomosis was performed in the area of sigmoid-rectal junction. Macroscopically, there were no visible metastases in the operation field. The surgery and postoperative period ran without any complications. On histopathological examination, the removed tumour was a well differentiated liposarcoma (WDL) stemming unusually from adipose tissue of colonic submucosa in an obese male. WDL is a hard to diagnose tumour, especially in early stages of its growth. In the presented case, the tumour was completely resected. PMID- 26816935 TI - Multifocal Bullous Fixed Drug Erruption Due To Phenytoin: A Lesson Learned! AB - Antiepileptic drugs (AED) are a common culprit of cutaneous eruptions in clinical practice. Phenytoin, lamotrigine and carbamazepine are the commonest offenders. Maculopapular eruptions are the most frequently reported events. However, multifocal bullous fixed drug eruptions have rarely been described in association with AED use. The risk factors for skin rash including its association with the rate of drug administration are unclear in the literature. We report a case of a young alcoholic man, on long term phenytoin therapy since 3 years, who presented to our emergency department with a breakthrough seizure episode. Patient's routine investigations including serum biochemistry, imaging and toxicology screen were normal. Patient was found to have sub-therapeutic serum phenytoin levels and was prescribed loading with intravenous phenytoin (15mg/kg body weight), which was mistakenly infused at a rapid rate (60mg/minute). Patient developed multifocal bullous lesions over muco-cutaneous regions after 6 hours of drug administration which healed after its discontinuation leaving behind residual hyperpigmentation. Patient was managed conservatively, switched to oral levetiracetam and discharged in a stable condition after one week of hospital stay. Present case highlights a yet uncommon reaction to a commonly used drug and tries to establish the relation between rate of drug infusion and the risk of skin reaction. PMID- 26816936 TI - HSV Encephalitis with Normal CSF - A Case Report with Review of Literature. AB - Herpes simplex virus encephalitis (HSVE) is one of the most potentially fatal infectious disease that should be detected as early as possible. The combination of clinical history and examination, brain computed tomography or magnetic resonance imaging (MRI) and lumbar puncture have been used to establish a diagnosis. The authors present a case of HSVE with normal CSF analysis, but typical MRI findings consistent with HSE and CSF PCR positive for Herpes simplex virus1 DNA, who responded to Acyclovir therapy with complete recovery. PMID- 26816937 TI - Interstitial Lung Disease in Systemic Scleroderma, Complicated with Bilateral Pulmonary Aspergilloma: An Unusual Association. AB - Aspergilloma or mycetoma is a saprophytic fungal infection that colonizes pre existing excavated lung lesion. However, its association with systemic sclerosis related interstitial lung disease is unusual and scarcely found in literature. We report a middle aged female with long standing systemic sclerosis, who was on immunosuppressive therapy for many years, presented with repeated haemoptysis. Although provisionally pulmonary tuberculosis was suspected, imaging investigations showed presence of bilateral masses inside bullous air spaces along with air-crescent sign suggestive of fungal ball. Subsequent Computed tomography guided needle aspiration from lung mass confirmed Aspergillus fumigatus as aetiologic agent on fungal culture. Patient was treated conservatively for haemoptysis and with oral antifungal drug as surgical removal of fungal ball was not an option due to poor pulmonary reserve. Although she had been treated with itraconazole for more than three years, she had recurrent haemoptysis during this period without any significant regression of size of the aspergilloma. Management of aspergilloma in a background of extensive interstitial lung disease remains poorly defined and complicated. Thereby, overall prognosis is unfavourable and depends on evolution of both underlying scleroderma as well as aspergilloma. PMID- 26816938 TI - Croton membranaceus Improves Some Biomarkers of Cardiovascular Disease and Diabetes in Genetic Animal Models. AB - INTRODUCTION: Cardiovascular disease (CVD) accounts for 17.3 million deaths per year globally. In Ghana, CVD accounts for 22.2% of deaths. Croton membranaceus (CM) Mull. Arg. (Euphorbiaceae), a medicinal plant in Ghana is mainly used traditionally for the treatment of benign prostatic hyperplasia and measles. However, some hypoglycaemic and hypotensive effects have recently been reported but not scientifically examined. AIM: The study aimed at establishing whether Croton membranaceus (CM) used for prostatitis had any effect on CVD markers. MATERIALS AND METHODS: In experiment 1, lipid profile changes were determined. Twenty four male Spontaneously Hypertensive Rats (SHR) were divided into 4 groups. Low (LD), intermediate (ID) and high dose (HD) groups received 25, 50 and 100 mg/kg b.wt. CM aqueous root extracts (CMARE) for 60 days, respectively, the controls received distilled water. In experiment 2, blood glucose levels (BGL) were determined. 21 db/db mice were divided into 3 groups of 7 mice each alongside db/+ mice (7) (negative control). Groups 1 and 2 received 250 mg/kg b.wt CMARE and metformin, respectively. Group 3 (positive control) and db/+ mice (negative control) received distilled water. Mice were monitored for 15 hours. Data collected were analysed using SPSS version 20. RESULTS: Hypotriglyceridaemic effect was observed (p=0.005). High Density Lipoprotein cholesterol (HDL) and Low Density Lipoprotein cholesterol (LDL) showed significant increases (p=0.013) and decreases (p=0.003), respectively. A significant CRP reduction was observed for ID and HD groups (p = 0.010, p = 0.011, respectively). BGL was reduced in Metformin and Croton groups (p=0.000; p= 0.006, respectively) after 3 hours. CONCLUSION: In conclusion, CMARE has positive effects on some CVD biomarkers and a hypoglycaemic effect. PMID- 26816939 TI - Dysregulation of Glucose Homeostasis Following Chronic Exogenous Administration of Leptin in Healthy Sprague-Dawley Rats. AB - INTRODUCTION: Impaired glucose utilization is seen in chronic hyperleptinaemia associated conditions such as obesity and type 2 diabetes mellitus. It is unclear if this impaired glucose utilization is due to the effect of persistent hyperleptinaemia on insulin secretion from the beta cells of pancreas. AIM: To examine the effects of chronic leptin administration on plasma glucose regulation in rats. MATERIALS AND METHODS: Glucose challenge curves were plotted for male Sprague-Dawley rats treated with either normal saline (Control; n=8) or subcutaneous leptin injection for 42 days (60 MUg/kg body weight/day; n=8). Plasma glucose and plasma insulin levels were measured at 0, 5, 10, 15, 20 and 25 minutes after glucose challenege. Skeletal muscle tissue was collected at the end of a glucose challenge for glucose transporter-4 protein content, insulin receptor and glucose transporter-4 mRNA expression. Data were analysed using repeated measures and one-way ANOVA with post-hoc analysis. RESULTS: Chronic leptin treatment caused significantly higher fasting insulin level. Post glucose challenge, there was a significant increase in blood glucose levels and insulin level in the leptin treated rats. There was no significant difference in the skeletal muscle glucose transporter-4 content. However, leptin treated rats showed decreased mRNA expression of Insulin Receptor and glucose transporter-4 in the skeletal muscle. CONCLUSION: Leptin administration for 42 days caused hyperinsulinaemia and decreased the expression of insulin receptors in insulin sensitive tissues leading to the development of an insulin resistance-like state in the rats. PMID- 26816941 TI - Can Postoperative Nutrition be Favourably Maintained by Oral Diet in Patients with Emergency Temporary Ileostomy? A Tertiary Hospital Based Study. AB - INTRODUCTION: Temporary ileostomy is an emergency procedure performed in cases having septic peritonitis in presence of perforation or obstruction or gangrene of small intestine. These patients usually suffer from gross malnutrition following surgery. AIM: To measure nutritional status of patients with emergency temporary ileostomy and to determine whether their postoperative nutrition can be favourably maintained by oral diet alone. MATERIALS AND METHODS: Sixty patients were enrolled for the study on the basis of inclusion and exclusion criteria during the study period from January 2012 to December 2013. Oral feeding was started as soon as ileostomy started functioning and patients expressed hunger, about 48-72 hours postoperatively. An individualized diet chart was formulated for each patient using Harris Benedict Equation. Nutritional assessment was done on 1) 1(st) day of oral feeding, 2) After 7 days of oral feeding, 3). After three months of oral feeding. Nutritional parameters (anthropometric, biochemical) employed were tabulated and statistically analysed with SPSS v 17, Chicago. RESULTS: Out of 60 patients, 36 males and 24 females were enrolled in the study. The patients were in the age group of 20-60 years with a mean age of 45 years. After 7 days of oral nutrition the nutritional status deteriorated with a significant decrease in body weight (p<0.001) and serum haemoglobin (p <0.001). However, at the end of the study, the patients had their nutritional status restored satisfactorily with normalization of basic parameters like bodyweight, haemoglobin and serum albumin (p<0.001). CONCLUSION: Proper dietary advice and oral nutrition were found to be sufficient for gradual restoration and maintenance of satisfactory nutritional status in the postoperative period. PMID- 26816940 TI - Frenulum Sparing Circumcision: Step-By-Step Approach of a Novel Technique. AB - OBJECTIVE: Circumcision, by most conventional methodologies, involves division of the frenulum and excision of the entire foreskin covering the glans. This seemingly simple procedure is occasionally associated with dreadful and devastating complications. We describe a new frenulum-sparing technique that circumvents some of the potential complications of conventional techniques and could also potentially help preserve preputial role in sexual function. MATERIALS AND METHODS: An initial dorsal slit, three fourths of the way up to the corona is extended laterally and obliquely on either side, to meet the preputial edge, 3-4 mm from the frenulum. A broad sleeve of sub-coronal mucosa is thus preserved. The frenulum is left untouched, leaving a wide skin bridge connecting the mucosal sleeve with the shaft skin. The raw area is closed with interrupted, synthetic absorbable sutures. Over a three year period, 42 patients were circumcised using this technique. RESULTS: No significant complications like frenular bleed, painful postoperative erections, chordee, meatal stenosis, or urethra-cutaneous fistula were observed in any patient. The cosmetic results were pleasing. CONCLUSION: The frenulum-sparing technique of circumcision is a promising modification to the various existing techniques. The method described is technically easier to perform than conventional frenulum-dividing procedures and has an acceptable cosmesis. Further randomised controlled studies on larger cohorts are necessary to establish the true benefits of this technique over established procedures. PMID- 26816942 TI - Predicting Difficult Laparoscopic Cholecystectomy Based on Clinicoradiological Assessment. AB - INTRODUCTION: Laparoscopic cholecystectomy (LC) is the gold standard treatment for symptomatic cholelithiasis. However, of all Laparoscopic cholecystectomies, 1 13% requires conversion to an open for various reasons. Thus, for surgeons it would be helpful to establish criteria that would predict difficult laparoscopic cholecystectomy and conversion preoperatively. But there is no clear consensus among the laparoscopic surgeons regarding the parameters predicting the difficult dissection and conversion to open cholecystectomy. AIM: To assess the clinical and radiological parameters for predicting the difficult laparoscopic cholecystectomy and its conversion. MATERIALS AND METHODS: This was a prospective study conducted from October 2010 to October 2014. Total of 180 patients meeting the inclusion criteria undergoing LC were included in the study. Four parameters were assessed to predict the difficult LC. These parameters were: 1) Gallbladder wall thickness; 2) Pericholecystic fluid collection; 3) Number of attacks; 4) Total leucocyte count. The statistical analysis was done using Z-test. RESULTS: Out of 180 patients included in this study 126 (70%) were easy, 44 (24.44%) were difficult and 3 (5.56%) patients required conversion to open cholecystectomy. The overall conversion rate was 5.6%. The TLC>11000, more than 2 previous attacks of cholecystitis, GB wall thickness of >3mm and Pericholecystic collection were all statistically significant for predicting the difficult LC and its conversion. CONCLUSION: The difficult laparoscopic cholecystectomy and conversion to open surgery can be predicted preoperatively based on number of previous attacks of cholecystitis, WBC count, Gall bladder wall thickness and Pericholecystic collection. PMID- 26816943 TI - Enterocutaneous Fistula: Different Surgical Intervention Techniques for Closure along with Comparative Evaluation of Aluminum Paint, Karaya Gum (Hollister) and Gum Acacia for Peristomal Skin Care. AB - INTRODUCTION: Gastrointestinal fistulas are serious complications and are associated with high morbidity and mortality rates. In majority of the patients, fistulas are treatable. However, the treatment is very complex and often multiple therapies are required. These highly beneficial treatment options which could shorten fistula closure time also result in considerable hospital cost savings. AIM: This study was planned to study aetiology, clinical presentation, morbidity and mortality of enterocutaneous fistula and to evaluate the different surgical intervention techniques for closure of enterocutaneous fistula along with a comparative evaluation of different techniques for management of peristomal skin with special emphasis on aluminum paint, Karaya gum (Hollister) and Gum Acacia. MATERIALS AND METHODS: This prospective observational study was conducted in the Department of Surgery, M.L.N. Medical College, Allahabad and its associated hospital (S.R.N. Hospital, Allahabad) for a period of five years. RESULTS: Majority of enterocutaneous fistula were of small bowel and medium output fistulas (500-1000 ml/24hours). Most of the patients were treated with conservative treatment as compared to surgical intervention. Large bowel fistula has maximum spontaneous closure rate compare to small bowel and duodenum. Number of orifice whether single or multiple does not appear to play statistically significant role in spontaneous closure of fistula. Serum Albumin is a significantly important predictor of spontaneous fistula closure and mortality. Surgical management appeared to be the treatment of choice in distal bowel fistula. The application of karaya gum (Hollister kit), Gum Acacia and Aluminum Paint gave similar outcome. CONCLUSION: Postoperative fistulas are the most common aetiology of enterocutaneous fistula and various factors do play role in management. Peristomal skin care done with Karaya Gum, Gum Acacia and Aluminum Paint has almost equal efficiency in management of skin excoriation. However, role of Gum Acacia was found to be good with inflamed, excoriated and ulcerative skin in comparison to Aluminum Paint and as efficacious as Karaya Gum but at much lower cost. PMID- 26816945 TI - Large Tubullo-villous Adenoma of Duodenum Presenting as Gastric Outlet Obstruction. AB - Tubullo-villous adenoma of duodenum is a rare entity. These are potentially malignant tumours and therefore, complete excision is the treatment of choice. However, at times preoperative diagnosis could not be always achieved posing difficulty in choosing the optimal surgical method of excision. We report a 40 year-old male patient presented with vague upper abdominal pain and vomiting for last 6 months. His computed tomography and endoscopy demonstrated intraluminal polypoidal mass. Endoscopic biopsies were negative for malignancy. Local surgical excision with tumour free margin was performed and histology revealed tubullo villous adenoma. PMID- 26816946 TI - Mesenteric Panniculitis: An Unusual Cause of Epigastric Pain. PMID- 26816944 TI - Placenta Percreta Presenting with Delayed Haematuria. AB - Placenta percreta presents as life threatening complications with bladder invasion. A condition of placenta invading urinary bladder presented with differential diagnosis of gestational trophoblastic neoplasia on imaging and responded to chemotherapy. A 35-year-old primi-gravida presented at term with per vaginal bleeding. During caesarian section placental mass totally invading uterine myometrium was found. She was given single dose of Methotrexate. After 2 months she presented with gross haematuria with clot retention two times. Her MRI was suggestive of gestational trophoblastic neoplasia of size 19 X 10 X 13cm. Her beta-Human Chorionic Gonadotropin levels were 691.23 mIU/ml. She was given total four doses of methotrexate. At present size of mass was 1.6 X1.3X 1.1cm. Her beta Human Chorionic Gonadotropin level dropped down to 2mIU/ml. Patient was not willing for further intervention or for follow up. PMID- 26816947 TI - A Novel Technique of Defattening Large Full Thickness Skin Grafts. PMID- 26816948 TI - Long Term Patient Satisfaction of Burch Colposuspension with or Without Concomitant Total Abdominal Hysterectomy. AB - INTRODUCTION: Urinary incontinence negatively affects the quality of life. Various methods are used in the treatment of stress incontinence. Burch colposuspension (BC) is the classical treatment of urinary incontinence. AIM: To compare the long-term satisfaction in patients receiving BC with or without concomitant total abdominal hysterectomy. MATERIALS AND METHODS: One hundred and twenty patients with stress incontinence underwent burch colposuspension with or without concomitant total abdominal hysterectomy. Ninety-three (77.5%) patients were interviewed by telephone. Of these, 91(75, 8%) patients agreed to participate in the study. The patients were divided into two groups according to the type of the surgical procedure. Group 1(N=48, 52.7%) had received burch colposuspension with concomitant total abdominal hysterectomy. Group 2 (N=43, 47.3%) had received burch colposuspension without concomitant total abdominal hysterectomy. RESULTS: In Group 1, 41 patients (85%) were satisfied with the surgery and did not complain of urinary incontinence (p<0.05). In Group 2, 37 (86%) patients were satisfied with the surgery (p<0.05). CONCLUSION: There were no difference in patient satisfaction between hysterectomy and BC and only BC to treat incontinence. PMID- 26816949 TI - Maternal Anaemia and Neonatal Outcome: A Prospective Study on Urban Pregnant Women. AB - INTRODUCTION: Maternal anaemia is a major contributor of adverse neonatal outcomes, particularly compromised birth weight and head circumference. OBJECTIVE: To assess the relationship between maternal anaemia and neonatal measures in a sample of low-middle income group urban mothers. MATERIALS AND METHODS: One hundred pregnant women with population representative prevalence of anaemia were enrolled. Socio-demographic, anthropometry, obstetric profile (parity, abortion history, food habits, gap period with last pregnancy etc), and systolic/diastolic blood pressure were documented. Neonatal outcomes (gestational age and type of delivery), and birth anthropometry (weight, length, and head circumference) were measured at delivery. Univariate and multivariate regression analysis for associating maternal haemoglobin levels and neonatal outcomes were performed. RESULTS: The anaemic and non-anaemic pregnant women differed significantly in interval between previous & index pregnancy (p=0.031), parity (p=0.009), systolic blood pressure (p=0.026), diastolic blood pressure (p=0.042), maternal Hb (p<0.01). The mean gestational age (p<0.01), weight (p<0.01), length (p<0.01) and head circumference (p<0.01) of the neonates differed significantly between the two groups. On using maternal haemoglobin as a continuous variable, these anthropometric birth outcomes were positively correlated with maternal haemoglobin (p<0.05). Further, univariate linear regression showed similar associations between maternal haemoglobin (g/dL) and birth weight (p=0.004), length (p=0.010) and head circumference (p=0.003). CONCLUSION: Maternal haemoglobin has a positive relationship with the neonatal measures of weight, length and head circumference. PMID- 26816951 TI - Successful Management of Live Cervical Ectopic Pregnancy: A Case Report. AB - Cervical pregnancy is a rare form of ectopic pregnancy with potential grave consequences occurring in approximately 1:9,000 deliveries. It is life threatening as the pregnancy is implanted in the endocervical canal and the trophoblast can penetrate through the cervical wall and into the uterine blood supply resulting in catastrophic haemorrhage. Historically, the treatment had been hysterectomy because of the considerable risk of life-threatening haemorrhage, but in the recent past various conservative management modalities have been applied to preserve fertility. Here, we report a case of successful (both medical and surgical) management of cervical ectopic pregnancy in a young woman. A 29-year-old, gravid 2, para1 and living 1 with previous caesarean section had presented with mild bleeding per vagina for 5 days following 7 weeks of amenorrhoea. Past menstrual, medical, surgical and family history were unremarkable except the previous caesarean section. On examination vital signs were normal but pelvic examination revealed a distended cervix with bulky uterus, without anyadnexal mass or tenderness and no cervical motion tenderness. Further transvaginal sonography showed a live cervical gestation of 7 weeks and 4 days and serum beta-HCG value of 1,03,113mIU/ml. Patient received conservative approach with combination of intraamniotic potassium chloride and methotrexate and suction curettage. Due to conservative approach emergency hysterectomy and blood transfusion was avoided. PMID- 26816950 TI - Umbilical Cord Haematoma Causing Still Birth- A Case Report. AB - Still birth continues to be one of the many challenges that an obstetrician has to face. Still births that occur in the antenatal period are more difficult to explain than that which occurs intrapartum. The latter is most often due to intrapartum asphyxia, medical complications or infections; however a cause for antenatal still birth is difficult to ascertain. A thorough examination of the case along with necessary investigations might not necessarily reveal any cause and this leads to considerable anxiety for both the mother and the treating obstetrician. In the investigation of a case of still birth a detailed examination of the placenta and cord has to be emphasised as a considerable number of still births that are thought to be unexplained may be attributable to placental or cord pathologies. Here we present one such case where an umbilical cord haematoma resulted in intrauterine foetal death. PMID- 26816952 TI - Prenatal Diagnosis of Tectocerebellar Dysraphia with Occipital Encephalocele. AB - Tectocerebellar dysraphia (TCD) is an extremely rare disorder and comprises the congenital abnormalities including occipital encephalocele, aplasia and/or hypoplasia of cerebellar vermis and deformity of tectum. Only few reported cases of this entity are there in the literature. However, the diagnosis in each of the previous cases had been made after birth. We herein describe the first reported case of prenatal diagnosis for TCD in a Turkish woman. PMID- 26816953 TI - A Case Series on Gossypiboma - Varied Clinical Presentations and Their Management. AB - Retained surgical sponges in the peritoneal cavities are an infrequent operative/surgical complication and an error which is avoidable. The unfortunate situation of forgotten or missed foreign bodies after any surgical procedure may lead to medico legal problems. Though gossypiboma can be found at any operative site but intraperitoneal cavity is the most frequent site reported in literature. Over a period of three years, June 2009-2012, we conducted retrospective analysis of case summaries of eight patients who underwent re-laparotomy for retained surgical sponge at our institute. Pre operative diagnosis was made in 7out of 8 patients, 5 of whom underwent re-laparotomy and one had sponge removed through the caesarean incision, while in another it was removed per-vaginum through the open vault (post hysterectomy). In one patient, gossypiboma was an incidental finding on laparotomy done for adnexal mass. There was no mortality in any of the cases. PMID- 26816954 TI - Correlation among Radiographic, Arthroscopic and Pain Criteria for the Diagnosis of Knee Osteoarthritis. AB - INTRODUCTION: Osteoarthritis (OA) is the most common degenerative joint disorder leading to functional impairment and dependency in older adults. Early detection and intervention is of paramount importance in decreasing the morbidity. Radiography is the first investigation of choice for OA patients presenting with knee pain. But, there is a high degree of discordance between clinical and radiographic findings. Arthroscopy aids in accurate diagnosis of OA knee. AIM: In view of the conflicting reports in the literature the present study was undertaken to report the correlation among radiographic, arthroscopic and pain findings in knee OA patients to facilitate early and precise diagnosis. MATERIALS AND METHODS: Twenty eight cases (14 males and 14 females) of primary OA knee (7 each from radiographic grade 1 to 4) were screened and selected for the study. Spearman's rank correlation coefficients (Rho/r estimate) were calculated to determine the relationship between pain, radiographic and arthroscopic grades in patients with knee OA. RESULTS: Among 28 patients, 10.71% had grade 1, 14.28% had grade 2, 25% had grade 3 and 50% had grade 4 arthroscopic findings. Overall Spearman's correlation coefficient (r) for radiographic and arthroscopic grades was 0.8077, 0.8212 for radiographic and pain grades and 0.7634 for arthroscopic and pain grades. Correlation coefficient could not be calculated for individual grades in isolation which would otherwise represent the factual correlation. The Mean arthroscopic grade for radiographic grades 1 to 4 were 1.57, 3.42, 3.57,4.0 respectively and the Mean pain grades for radiographic grades 1 to 4 were1.57, 2.57,3.28, 3.57 respectively. Radiological findings were found to lag behind the arthroscopic findings significantly. CONCLUSION: Arthroscopic findings represent the exact extent and degree of the pathology of OA knee. Kellgren-Lawrence grading read with conventional Antero-posterior standing radiographs of knee underscores the arthroscopic findings significantly in grades 1, 2 and 3. Radiological and clinical findings (Apley's pain grading) in combination should be considered in concluding the final diagnosis and treatment of OA knee. Improvised criteria for precise diagnosis have to be evolved. PMID- 26816955 TI - Double Tension Band Osteosynthesis in Inter-Condylar Humeral Fractures. AB - INTRODUCTION: Intercondylar humerus fractures are uncommon in orthopaedic practice. The treatment for the same has been described in the literature and include paragonal and orthogonal fixation by using plates. Tension band wiring as a treatment for the same is sparsely described in the literature. AIM: To evaluate the effectiveness of "Double Tension Band wiring" method for the treatment of intercondylar fractures of humerus and compare the results with studies involving treatment with locked plates. MATERIALS AND METHODS: Twenty patients, all presenting with fresh fractures of the distal humerus, treated with double tension band wiring were retrospectively evaluated over a period of three years. Fractures were classified according to Jupiter classification of distal humeral fractures. There were 5 high T fractures, 13 low T fractures and 2 Y fractures. According to AO classification, all were C1 fractures. Average age of the patients was 56.20 years (32-70 years). There were 13 males and 07 females. RESULTS: Out of 20 cases treated with this method, rigid fixation and union was achieved in all of them. The average tourniquet time was 69 minutes with minimum of 50 minutes and maximum of 120 minutes. Radiological union was achieved at an average of 10.8 weeks (8-14weeks). Average range of motion was 104.5 degrees with maximum range of motion 120 degrees (10-130) and minimum of 70 degrees (30-100). Excellent or good results were obtained in 80% of the patients in our study. CONCLUSION: Double tension band is a reliable, less demanding and cost effective method of fixation of intercondylar fractures of humerus. PMID- 26816956 TI - A Rare Occurrence of Enchondroma in Neck of Femur in an Adult Female: A Case Report. AB - Enchondroma is a solitary, benign, intramedullary cartilaginous tumour occurring most commonly in small bones of hands and feet. Distal femur and proximal humerus are other less common locations. Enchondroma consists of 3-10% of all bone tumours, while they constitute 12-24% of benign bone tumours. They originate from the growth plate cartilage which later on proliferates to form enchondroma. Radiographs reveal a localized, radiolucent lytic bone defect usually with punctuate calcifications. Lesions are central or eccentric and metaphyseal involvement most commonly for long bones. MRI and histopathological examination can be used to confirm the diagnosis. Asymptomatic cases can be managed conservatively with serial radiological follow ups. Cases with symptoms are managed operatively. Recurrence rate is very low (<5%), it suggests malignancy. We here present a case of a 30-year-old female patient who presented with a history of pain in right hip since 7 months. Radiological examination showed the lesion to be enchondroma. The patient was managed by curettage with autogenous iliac bone graft & prophylactic 6.5 mm cannulated screws fixation. Histopathology confirmed the lesion to be enchondroma. At the latest follow up after 6 months, the patient was symptom free and there was no evidence of any recurrence. The current case report of enchondroma located in the neck of femur signifies the importance of early diagnosis, timely intervention and treatment. Also, this case report represents one of the very rare cases reported in literature. PMID- 26816957 TI - Osteochondroma of Upper Dorsal Spine Causing Spastic Paraparesis in Hereditary Multiple Exostosis: A Case Report. AB - Osteochondroma of the spine is rare. It may present in solitary or multiple form (hereditary multiple exostoses). Herein, we report a case of an 18-year-old male who was diagnosed with thoracic osteochondroma, originating from the D4 vertebra with intraspinal extension and spinal cord compression in hereditary multiple exostosis. The patient was managed with surgery. Complete tumour excision was done to relieve cord compression and recurrence. Postoperatively the patient's symptoms were improved. At 2.5 year follow-up patient is doing well without any recurrence. PMID- 26816958 TI - A Rare Combination of Ipsilateral Partial Talocalcaneal and Talonavicular Coalition. AB - Tarsal coalitions refer to fibrous, cartilaginous or osseous fusion between two tarsal bones. Commonly seen are talocalcaneal coalitions and calcaneonavicular coalitions. Talonavicular, calcaneocuboid and cubonavicular coalition are very uncommonly seen. Talocalcaneal and calcaneonavicular coalitions are generally symptomatic whereas talonavicular coalitions are asymptomatic. Special view radiography, CT and MRI will be helpful in diagnosing coalitions depending on nature of coalitions. In this case report, we present 24-year-old male patient with rare combination of talocalcaneal and talonavicular coalition on ipsilateral side. Patient also showed talar beak sign and arthritic changes at subtalar joint. Considering first time presentation to hospital and milder symptoms, we treated patient conservatively with short leg cast and foot orthoses. With course of treatment, symptoms were relieved significantly. PMID- 26816959 TI - Morbidity and Mortality Pattern in Late Preterm Infants at a Tertiary Care Hospital in Jammu & Kashmir, Northern India. AB - INTRODUCTION: The morbidity and mortality pattern in late preterm infants is higher than term infants (gestational age >= 37weeks). The main reason behind that is the relative physiologic and metabolic immaturity, though there is no significant difference in the weight or the size of the two groups. AIM: The present study was undertaken to study the incidence, early neonatal morbidity and mortality (within first 7 days of life) in late preterm infants (34 - 36 6/7 weeks). MATERIALS AND METHODS: It was a hospital based prospective study conducted from April 2012 to March 2013. The study was conducted in the Department of Paediatrics and Neonatology at G.B. Pant General Hospital and Department of Gynaecology and Obstetrics L.D hospital and G.B. pant general hospital, (associated hospitals of Government Medical College, Srinagar). RESULTS: A total of 4100 neonates were included in the study. Incidence of late preterm neonates was 11.58 %. Three hundred sixty five (76.8%) of late preterm and 965 (28.3%) of term infants had at least one of the predefined neonatal conditions. Late preterm infants were at significantly higher risk for overall morbidity due to any cause (p<0.0001), respiratory morbidity (p<0.0001), mechanical ventilation (p=0.0002), jaundice (p<0.0001), hypoglycaemia (p<0.0001), and sepsis (p<0.0001) Perinatal asphyxia (p= 0.186). Early neonatal mortality in late preterm neonates was 2.5% or 25/1000 live births. CONCLUSION: Compared with term infants, late preterm infants are at high risk for overall morbidity, respiratory morbidity, and need of mechanical ventilation, jaundice, hypoglycaemia & sepsis. They also have a higher mortality as compared to term neonates. PMID- 26816960 TI - Thrombocytopenia in Paediatric ICU: Incidence, Transfusion Requirement and Role as Prognostic Indicator. AB - INTRODUCTION: Thrombocytopenia is defined as platelet count less than 150*10(9)/L, it has a greater incidence in Intensive Care Units (ICUs) compared to wards and its most common cause is increased platelet consumption. AIMS: To investigate incidence of thrombocytopenia, platelet transfusions requirement, associated diseases and relationship between thrombocytopenia and mortality. MATERIALS AND METHODS: Eleven months hospital records between October 2013 and August 2014 of the PICU in a tertiary care teaching hospital was investigated retrospectively and 275 critically ill children formed the sample. STATISTICAL ANALYSIS: Odds ratio with 95% confidence interval was used. Probability value (p value) of less than 0.05 was considered statistically significant. Results were confirmed using chi(2) test. RESULTS: Out of 275 patients {168 males (61.09%) and 107 females (38.91%)}, 89 patients had thrombocytopenia. Out of these 89 patients, 43 patients (48.31%) had severe, 24 patients (27.91%) had moderate and 22 patients (24.72%) had mild thrombocytopenia. The 43 patients having severe thrombocytopenia received platelet transfusion and out of these 43 patients 24 (55.81%) received more than one transfusion and 18 (41.86%) of the transfused patients expired. Among thrombocytopaenic patients, Sepsis (25.84%) was the most common diagnosis followed by Pneumonia (19.10%), Meningitis (13.48%), Diabetic Ketoacidosis (5.62%), Enteric fever (7.86%), Tubercular Meningitis (3.37%), Infantile Tremor Syndrome (2.25%), Congenital heart disease (5.62%), Burns(3.37%), Brain Haemorrhage (2.25%%), Hepatic abscess (1.12%), Chronic Renal Failure (3.37%), Malaria (2.25%) and Hepatitis (4.49%). There is a statistically significant association between thrombocytopenia and mortality. A significant association was established between mortality in thrombocytopenic patients of sepsis. CONCLUSION: Thrombocytopenia is commonly associated with sepsis. Mortality rate is higher in thrombocytopenic patients. PMID- 26816961 TI - Clinical, Biochemical and Outcome Profile of Biotinidase Deficient Patients from Tertiary Centre in Northern India. AB - INTRODUCTION: Biotinidase deficiency is an inherited metabolic disorder with estimated birth incidence of 1 in 61,000 for profound and partial deficiency. Estimated incidence of profound and partial biotinidase deficiency is 1 in 1, 37,000 and 1 in 1, 10,000 respectively. The carrier frequency in general population is 1 in 120. We attempt to study clinical, biochemical and outcome from 10 Biotinidase deficient patients. MATERIALS AND METHODS: A retrospective case record study was conducted to record Clinical, biochemical and outcome profile from genetic records. Biotinidase level was measured using spectrophotometric method. RESULTS: Study group comprised of 8 males and 2 females with median age of presentation 6 (2-45.75) months. Median (interquartile range) Biotinidase level in study group 0.3 (0.08-1.5) nmol/ml/min. Study group was further divided in to early onset group (< 12 months, n-6) and late onset group (> 12 months, n-4). Seizure, alopecia and hearing loss were predominant phenotypes in study group. The other rare presentations were: hypotonia, ataxia, skin rash, seborrhoea. The most common seizure type was focal seizure. Control of seizure activity was important immediate outcome measured in study group. Median duration (interquartile range) of seizure control in early onset group was 3 (2 4)days against 13.5 (12.25-14.75) days in late onset group. CONCLUSION: This study highlights the need of early diagnosis for favourable outcome for a potentially treatable inherited metabolic disorder. PMID- 26816962 TI - Functional Neonatal Echocardiography: Indian Experience. AB - INTRODUCTION: Functional echocardiography, as opposed to echocardiography as performed by the cardiologist, is the bedside utilization of cardiac ultrasound to take after functional and haemodynamic changes longitudinally. Information reflecting cardiovascular capacity and systemic and pulmonary blood flow in sick preterm and term neonates can be observed utilizing this strategy. Information is lacking on its use in neonatal units in India. AIM: To characterize the impact of Functional neonatal echocardiography (FnECHO) programme on decision making in a tertiary care centre in India by evaluating its frequency of use, patient characteristics, and indications. MATERIALS AND METHODS: Prospective observational study of neonates in a tertiary Neonatal Intensive Care Unit (NICU) in Pune (India) from February 2014 to January 2015. All the neonates undergoing FnECHO during this 12 month period based on clinical findings were included in the study. Data extracted from the review of the clinical notes included gestational age, birth-weight, mode of delivery, Apgar scores, details of respiratory and cardiovascular support, timing of FnECHO and any other clinical diagnosis. The findings of echocardiography were recorded and correlated with the clinical and other laboratory or X-ray findings. If these findings indicated a change in management, it was instituted. RESULTS: A total of 348 echocardiographic studies were performed in 187 neonates (mean 1.86; SD 2.02). The most frequent indication was Patent Ductus Arteriosus (PDA) assessment (n= 174, 50%), followed by haemodynamic instability (n=43, 12.36%). The results of FnECHO modified treatment in 148 cases (42.50%) in the form of addition and/or change in the treatment or avoidance of unnecessary intervention. CONCLUSION: FnECHO is frequently used in the NICU setting and may be a useful tool to guide treatment. PDA assessment and haemodynamic instability are the most frequent indications. To validate its usefulness, well co-ordinated large prospective studies are needed. PMID- 26816963 TI - Prevalence of Nosocomial Diarrhea Due to Adenoviruses 40 and 41 in a Paediatric Ward in Iran. AB - BACKGROUND: Enteric adenoviruses 40 (Ad40) and adenovirus 41 (Ad41) have been shown to be a significant cause of paediatric gastroenteritis worldwide, but no data are available for nosocomial diarrhea due to adenovirus in Iran. AIM: The present study was performed to determine the incidence of Ad40 and Ad41 in children less than five years with nosocomial diarrhea in Shahrekord, southwest Iran. MATERIALS AND METHODS: Adenovirus was detected by polymerase chain reaction (PCR) in stool samples collected during one year (2010-2011) from children less than five years with nosocomial diarrhea admitted to a paediatric center in Shahrekord, Iran. Nosocomial diarrhea was defined as those occurring more than 72 hours after admission to hospital for non-diarrheal causes. PCR technique was used for investigation of Ad40 and Ad41. RESULTS: In total of 100 samples, Ad40 and Ad41 DNA was found to be positive in 14/100 (14%), and 8/100 (8%) of diarrheic patients less than five years, respectively. CONCLUSION: Ad40 and Ad41 are important causes of nosocomial diarrhea in less than five-year, hospitalized Iranian children. PMID- 26816964 TI - Robinow Syndrome: A Rare Diagnosis. AB - Robinow syndrome is a rare entity characterized by short stature and abnormalities of the head, face and external genitalia. It is otherwise called 'fetal face syndrome' due to its resemblance with fetal face. We present an eight year-old female child who came with mesomelic short stature, abnormal facial features, multiple sets of teeth (both deciduous and permanent), pectus excavatum, umbilical hernia, limb abnormalities like shortening of fore arm, simian crease, broad thumbs and other fingers, clinodactyly, abnormal carrying angle, absent labia minora, absent clitoris. Apart from physical appearance she was having diversification of recti and umbilical hernia. Due to the several physical presentation mild systemic involvement it was diagnosed as autosomal dominant robinow syndrome. She is now on follow up and planned for a cosmetic surgery to repair facial defects. PMID- 26816965 TI - The Role of Potentially Retrievable Inferior Vena Cava Filters in High-Risk Patients Undergoing Joint Arthroplasty. AB - INTRODUCTION: Some patients undergoing total joint arthroplasty are at increased risk for venous thromboembolism (VTE). The aim of the present study was to evaluate the safety and efficacy of prIVCF in preventing PE in patients undergoing joint replacement surgery who are at high-risk for VTE. MATERIALS AND METHODS: In this prospective, IRB-approved study, prIVCF were placed in consecutive patients who met specific high-risk criteria (history of VTE or hypercoaguable state) prior to total joint arthroplasty. Patients were followed until the IVC filter was removed. Outcomes and complications were recorded per Society of Interventional Radiology guidelines. RESULTS: One hundred and nine potentially retrievable IVC filters were placed in 105 patients, who all subsequently underwent joint arthroplasty. One hundred eight IVC filters (98.9%) were retrieved successfully in a mean time of 44.1 days (range 13-183 days). There was 1 failed IVC filter retrieval attempt (0.9%) at 46 days post implantation. Two patients (1.9%) presented with recurrent PE and were successfully treated with anticoagulation prior to IVC filter retrieval. There were no fatalities from perioperative PE. In 1 patient (0.9%), a fractured filter leg had embolized during retrieval. CONCLUSION: Potentially retrievable IVC filters are safe and effective for prophylaxis against PE in patients at high risk for VTE undergoing joint arthroplasty. PMID- 26816966 TI - MRI Evaluation of Post Core Decompression Changes in Avascular Necrosis of Hip. AB - INTRODUCTION: Avascular necrosis of hip typically presents in young patients. Core decompression in precollapse stage provides pain relief and preservation of femoral head. The results of core decompression vary considerably despite early diagnosis. The role of MRI in monitoring patients post surgically has not been clearly defined. AIM: To study pre and post core decompression MRI changes in avascular necrosis of hip. MATERIALS AND METHODS: This is a contiguous observational cohort of 40 hips treated by core decompression for precollapse avascular necrosis of femoral head, who had a baseline MRI performed before surgery. Core decompression of the femoral head was performed within 4 weeks. Follow up radiograph and MRI scans were done at six months. Harris hip score preoperatively, 1 month and 6 months after the surgery was noted. Success in this study was defined as postoperative increase in Harris hip score (HHS) by 20 points and no additional femoral collapse. End point of clinical adverse outcome as defined by fall in Harris hip score was conversion or intention to convert to total hip replacement (THR). MRI parameters in the follow up scan were compared to the preoperative MRI. Effect of core decompression on bone marrow oedema and femoral head collapse was noted. Results were analysed using SPSS software version. RESULTS: Harris hip score improved from 57 to 80 in all patients initially. Six hips had a fall in Harris hip score to mean value of 34.1 during follow up (9 to 12 months) and underwent total hip replacement. MRI predictors of positive outcome are lesions with grade A extent, Grade A & B location. Bone marrow oedema with lesions less than 50% involvement, medial and central location. CONCLUSION: Careful selection of patients by MR criteria for core decompression provides satisfactory outcome in precollapse stage of avascular necrosis of hip. PMID- 26816967 TI - Bilateral Krukenberg Tumours Diagnosed Primarily by Transabdominal Sonography- A Case Report. AB - Krukenberg tumour, also known as carcinoma mucocellulare, is a metastatic adenocarcinoma of ovaries from different primary tumour sites. Gastric carcinoma is most common primary tumour responsible for approximately 50% of Krukenberg tumours. Discrimination between primary ovarian cancer and metastatic tumours in the ovary is important, because their management is different. Here we present a case of female suffering from gastric carcinoma with bilateral Krukenberg tumours, diagnosed primarily by transabdominal sonography. The patient was referred to higher centre for further treatment and followed up. PMID- 26816968 TI - Proximal Interruption of the Pulmonary Artery: A Case Series. AB - We present a few cases of Proximal Interruption of the Pulmonary Artery, an uncommon developmental anomaly associated with congenital heart disease. The cases had varied clinical presentations. Chest radiograph showed a hypoplastic lung with an ipsilateral small hilum on the side of the interruption and hyperinflation of the contralateral lung. Contrast CT confirmed the diagnosis, demonstrating non-visualization of the left or right pulmonary artery, and other related findings. PMID- 26816969 TI - High Resolution Ultrasound in Disseminated Soft Tissue, Muscular and Glandular Cysticercosis. PMID- 26816970 TI - Tubular Ectasia of Rete Testis with Spermatocele. PMID- 26816971 TI - Mesenteric Lymphangioma Presenting as Ileal Volvulus. PMID- 26816972 TI - Imaging in Rare and Atypical Sinonasal Masses: An Interesting Case Series. AB - Sinonasal tumours present a myriad of radiographic findings. While many of these tumours have been well described with regard to their typical sites of origin, age group and radiological appearance we have come across lesions in our daily practice which are exceedingly rare with regard to site of origin in sinonasal cavity. The radiological appearances of 4 such rare and unusual tumours arising in sinonasal region evaluated by cross sectional imaging (CT/MRI) have been illustrated in this article with a purpose to review the radio-pathological correlation of these tumours and to explain the utility of cross-sectional imaging CT and MRI in exploring diagnostic clues. Morphological features and radiological patterns of each tumour have been graded into mild, moderate and severe based on the extent of tumoural involvement. This review is intended to acquaint radiologists with the appearance of atypical sinonasal masses and their radiological appearance on cross sectional imaging to make an early diagnosis. PMID- 26816973 TI - Comparison between Transdermal Buprenorphine and Transdermal Fentanyl for Postoperative Pain Relief after Major Abdominal Surgeries. AB - INTRODUCTION: Opioid is generally regarded as an important part of multimodal, perioperative analgesia, especially for moderate to severe pain. Amongst the various modes of delivery transdermal route has several potential benefits over oral and parentral administration. These include noninvasive dosing, better absorption and lack of first-pass metabolism. A transdermal drug delivery system provides steady and continuous drug delivery resulting in steady plasma concentration. Bolus dosing of systemic analgesic results in supra and sub therapeutic plasma resulting in toxic and sub analgesic plasma drug concentration. It also improves patient compliance. MATERIALS AND METHODS: Sixty patients undergoing major abdominal surgery under GA were randomly divided in two groups (n=30). Group A received buprenorphine 10 mcg/h TDS and group B received 25 mcg/h fentanyl TDS, 6 hours prior to surgery. Patients were followed for three days for postoperative pain relief and adverse effects. RESULTS: Baseline and demographic variables are comparable in both groups. The mean level of VAS was significantly lower in group B as compared to group A at Day 1, 2 and 3. The mean level of sedation score was significantly lower in Group B than Group A. Haemodynamic variables in both groups (SBP, DBP and HR), shows comparable values in both groups and no significant difference was observed. Five out of 30 (16.7%) patients in group A required single dose of rescue analgesic while 0 out of 30 patients (0.00%) in group B required rescue analgesic. This difference in rescue analgesic requirement in not quiet statistically significant (p-value 0.0522). Twenty percent patient in fentanyl group and 16.7% patients in buprenorphine group experienced some adverse effects. Nausea and vomiting were main side effects of the drugs. The incidence of nausea and vomiting were 6.7% and 10% in buprenorphine and fentanyl group respectively. CONCLUSION: Fentanyl and buprenorphine TDS were effective and safe in controlling postoperative pain. Fentanyl is better than buprenorphine in this respect. PMID- 26816974 TI - Repositioning of Misplaced Central Venous Catheter with Saline Injection Under C Arm Imaging. AB - Malposition of central venous catheter is a well known technical complication. Misplaced catheter often requires reinsertion for proper placement of the catheter in the superior vena cava (SVC) to support safe delivery of care and minimize complications. But reinsertion exposes the patient once again to risks of complications related to the procedure including potential of misplacement. Literature describes only a few techniques for repositioning a misplaced central venous catheter (CVC). We tried old simple method of saline injection with force under image intensifier using hydrostatic force of intravenous fluid to straighten the CVC. We could successfully reposition two misplaced CVC's using this method. PMID- 26816975 TI - Usefulness of Gamma Glutamyl Transferase as Reliable Biological Marker in Objective Corroboration of Relapse in Alcohol Dependent Patients. AB - INTRODUCTION: The development of reliable diagnostic tool for assessing alcoholism is an utmost necessity in treating and preventing damage due to alcoholism to both individual and armed forces as alcoholism represents a serious health issue with major socioeconomic consequences. AIM: To observe, gamma glutamyl transferase (GGT) can serve the practical utility of firmly establishing alcohol dependence /relapse in Armed Forces patients and aid in fair disposals. MATERIALS AND METHODS: Fifty two consecutive cases of alcohol dependence syndrome admitted to a peripheral hospital were evaluated for the biological marker gamma glutamyl transferase (GGT) and compared against the gold standard of psychiatrist assessment. The cases were followed up for one year at three months, six months, nine months and 12 months interval. The GGT value of the cases was correlated with the abstinent /relapse status to find the cutoff levels of the GGT as a biological marker. RESULTS: At cutoff level of 50 IU/lit GGT exhibited specificity of 100% and sensitivity varying from 56% to 100%. At lower cut off levels chances of false positive cases with adverse consequences on service prospects of the individuals are high. The mean difference in GGT levels across relapse and abstinent group reached significant statistical proportion at admission and during follow-up at 3 months /6 months/9 months and 12 months. CONCLUSION: GGT can serve the practical utility of firmly establishing alcohol dependence syndrome in armed forces to aid in fair disposal of cases. It helps in providing motivational inputs to patients. Clinician should pay due consideration to clinical profile, ward observation and unit report as the diagnosis of alcohol dependence syndrome has serious implications towards service prospects of a soldier. PMID- 26816977 TI - A Clinico-Mycological Study on Suspected Cases of Chromoblastomycosis: Challenges in Diagnosis and Management. AB - INTRODUCTION: Verrucous plaques mimicking chromoblastomycosis are frequently seen in dermatology outpatient departments (OPD). However, no scientific evaluation has been carried out till date from eastern India. So this present endeavour is aimed at a thorough study of those cases to readdress the challenges in diagnosis and management in chromoblastomycosis from this part of the country. AIM: The study is to observe the incidence of proved chromoblastomycosis cases from clinically mimicking conditions and to note therapeutic prospects by use of different antifungal agents. MATERIALS AND METHODS: Twenty clinically suspected cases attending dermatology OPD were included in this study. Relevant histories were taken. Apart from routine hematological and biochemical investigations, scrapings from lesions were examined by direct microscopy with KOH wet mount, calcoflour white mount and fungal culture. Histopatholgical examination was also done. Any fungal growth was identified by growth characteristics and morphological features. RESULTS: Sclerotic bodies were detected in five samples. Of them three were found to be culture positive. Two growths were identified as Fonsecaea pedrosoi and one as Cladosporium carrionii. Rest 12 cases were diagnosed as either lupus vulgaris (3 cases; 15%), atypical mycobacterial infections (3 cases, 15%), Hypertrophic lichen planus (2, 10%), Hypertrophic DLE plaque (2; 10%), Wart (1, 5%) or fixed cutaneous sporothricosis (1, 5%), zygomycosis (1, 5%). Three cases (15%) were lost in follow up. Cases of chromoblastomycosis were managed with prolonged use of antifungal alone or in combination with saturated solution of potassium iodide and/or debridement. They were followed up for at least six months post treatment. CONCLUSION: A database comprising diagnostic clues and effective therapeutic intervention have been proposed for these rare subcutaneous mycoses. PMID- 26816976 TI - Exploring Health Situation of Indian Children with Autism Spectrum Disorder Using Autism Treatment Evaluation Checklist (ATEC) in an Urban Area of Odisha: A Case Study. AB - INTRODUCTION: Autism or Autism Spectrum Disorder (ASD) is a complex behavioural disorder in children with uncertain aetiology. Gastrointestinal metabolites have direct impact on brain function with possible role in its causation. Data on burden of Autism in India is sparse. AIM: The aim of the study was to determine the extent of social, communication and behavioural impairment among children suffering from ASD patientsin Odisha. MATERIALS AND METHODS: A cross-sectional study design was used to assess 20 children with ASD in Odisha using an autism treatment evaluation checklist to understand the extent of social, communication and behavioural impairment in them. Of these, 72% children were diagnosed with ASD within 2 to 2.5 years of age and 38.9% patients suffered from diarrhoea together with constipation at the time of the study. RESULT: There was moderate impairment in, subclasses I (Speech/language/ communication), II (sociability), III (sensory/ cognitive awareness) and overall score but mild impairment in subclass IV (i.e., health/ physical/behaviour). Possibly, the training programme of the school had positive impact on the behaviour and the health component. Severity of scores in subclasses was less in older children. There is need for training in order to improve the communication and social interaction domain of these children. CONCLUSION: This study has provided valuable insight into the health situation of children with ASD. The study has been carried out using ATEC checklist. It points towards the need for training in order to improve the communication and social interaction domain of these children. It also reinforces the necessity to carry out further studies to explore possible link of gastrointestinal metabolites in causing ASD and age related changes in ATEC score of these children. PMID- 26816978 TI - Multifocal Cutaneous Tuberculosis in Immunocompetent Individual. AB - Most common form of cutaneous tuberculosis (TB) is lupus vulgaris, which usually occurs in previously sensitized individuals who have a high degree of tuberculin sensitivity. Various forms including plaque, ulcerative, hypertrophic, vegetative, papular, and nodular forms have been described. We are reporting a case of a young female, who presented with 6 well defined erythematous scaly plaques involving both arms and a puckered scar on right forearm and right breast. Clinically, it was looking like lupus vulgaris with cold abscess, few lesions mimicking scrofuloderma, but skin biopsy from both the types of lesions revealed lupus vulgaris. Patient improved with Anti Tuberculous Therapy and surgical drainage of underlying cold abscess. PMID- 26816979 TI - Herpes Zoster Duplex Bilateralis in Immuno-Competent Patients: Report of Two Cases. AB - Herpes Zoster is a common viral disorder, occurs due to reactivation of latent Varicella Zoster Virus (VZV) usually in adults or elderly patients, usually confined to a single dermatome. Herpes zoster duplex is a rare but well established entity which is simultaneous, occurring of herpes zoster at two different non contiguous dermatomes, can be unilateralis or bilateralis. Here we are reporting two cases of herpes zoster duplex bilateralis, in case-1 lesions occurs in two different distant dermatomes while in case-2 it appeared in a single dermatome but both sides were involved. Both the patients were healthy immuno-competent male. PMID- 26816980 TI - Implication of Bifurcation of Abdominal Aorta for Radiotherapy Planning for Cervical Cancers. AB - INTRODUCTION: External Beam Radiotherapy plays a major role in the management of Carcinoma Cervix. The Radiotherapy treatment portals are designed to adequately cover the gross disease and areas of microscopic spread. The upper border of Radiotherapy field is traditionally placed at the level of L4-L5 intervertebral space to cover the common iliac nodal area. It is determined based on anatomical and surgical series which have shown that division of Abdominal aorta occurs at that level. AIM: To study the level of the division of abdominal aorta in relation to the lumbar vertebral levels. To propose the change in the upper border of Radiotherapy portals used in the treatment of Cervical Cancers. MATERIALS AND METHODS: Patients who underwent Radiotherapy for Cervical Cancer from December 2010 to January 2012 formed the subjects of this prospective study. All the patients underwent aquaplast immobilization in supine position and contrast enhanced Computed Tomography (CT) simulation for Radiotherapy planning following bladder protocol. The Radiotherapy planning was done on commercial treatment planning system, Prowess version 4.71. The level of division of Abdominal Aorta into right and left Common Iliac arteries with respect to vertebral level was determined and studied. RESULTS: The division of abdominal aorta into common iliac arteries occurred at the level of L3-L4 intervertebral space, in front of body of L4 vertebra and L4-L5 intervertebral space in 53.84%, 30.76% and 15.40% of the patients respectively. CONCLUSION: The division of abdominal aorta occurs at a higher level than L4-L5 intervertebral space in majority of patients. It is highly recommended to use CT scan based planning. However, in institutes where there are no facilities for CT based planning, it is advisable to shift the upper border of Radiotherapy treatment portal above the L3 L4 intervertebral space for delivering adequate doses to the common iliac lymphnodes. PMID- 26816982 TI - Osseous Metastases in Gynaecological Epithelial Malignancies: A Retrospective Institutional Study and Review of Literature. AB - INTRODUCTION: Osseous metastasis in gynaecological epithelial tumours is an extremely rare phenomenon occurring in less than 1% of these cancers. AIM: To analyse the clinical characteristics and prognosis in patients with gynaecological epithelial cancers with bone metastases. MATERIALS AND METHODS: This was a single institutional retrospective study done with the data available from January 2008 to January 2015. Out of 1686 patients with epithelial gynaecological malignancies there were a total 18 (1.07%) patients with osseous metastasis. Clinico-pathologic characteristics were tabulated in Microsoft Excel 2013 and data were analysed using SPSS software Version 21. A p-value< 0.05 was taken to be statistically significant. Survival analysis was done by using Kaplan Meier method and log-rank test was used to find out the difference in survivals. RESULTS: Out of the 18 gynaecological epithelial cancer patients with bone metastases, 12 had cervical cancer, three had ovarian cancer, two had endometrial carcinoma and one patient had vulvar malignancy. Twelve patients had squamous cell histology, while the rest had adenocarcinoma. The mean interval from primary diagnosis of cancer to the detection of bone metastases was 31.9 months (range, 1 - 60 months). Solitary bone lesion was present in seven patients. The most common site of bone metastasis was lumbar vertebra. Extra-osseous metastasis was present in 12 patients. The mean follow-up period was 8.3 months. During the follow-up period 12 out of the 18 patients died. There was significant difference in survival (p = 0.005) between patients with solitary bone metastasis and patients with multiple osseous metastases. Near significant survival difference (p = 0.056) was also noted in patients with extra-osseous metastases when compared to the patients without. Improved survival was also found in patients with controlled local disease (p = 0.003) when compared to patients with local failure. CONCLUSION: Bone metastasis in gynaecological epithelial malignancies is a rare phenomenon, but with grave prognosis. Multiple sites of bone involvement, recurrence at the primary tumour site and presence of other non-osseous metastases are poor prognostic indicators. Treatment in these patients should be tailored according to the patient's need. PMID- 26816981 TI - Phytomedicine in the Treatment of Cancer: A Health Technology Assessment. AB - INTRODUCTION: Cancer is reported to cause about 0.4 million deaths annually. The cost of diagnosis and treatment of cancer in India is enormous. AIM: This Health Technology Assessment (HTA) aims to understand the role, effect on mortality and adverse event occurrence, and cost effectiveness of phytomedicine in cancer treatment. MATERIALS AND METHODS: Health technology assessment by systematic review of published literature. An electronic literature search was performed in Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Medline, PubMed, Science Direct, SCOPUS, EMBASE, LANCET, and Google Scholar databases for randomized controlled trial, observational analytical studies, case control and cohort studies pertaining to phytomedicine and herbal medicine in cancer treatment published from 1987 till 2(nd) Novemeber 2014. Overall outcome measures collected included changes in mortality and adverse event profile. Cochrane Review Manager's Risk of Bias Table was used to assess the risk of bias. RESULTS: Out of 76 studies which were screened, 14 studies involving a total of 1965 participants (817 received various forms of phytomedicine or herbal medicine in addition to conventional therapy, and 1148 received conventional therapy only) suffering from various cancers (including cancers of the breast, prostate, nasopharynx, pancreas, stomach, ovary, non-small cell lung cancer and osteosarcoma), were included in this review. In comparison with conventional therapy, phytomedicine resulted in a significant reduction in mortality: Risk Ratio (RR) 0.67 (95% Confidence Interval (CI) 0.51 to 0.90). The combination of phytomedicine with conventional therapy resulted in a significant reduction in adverse drug reactions: RR 0.62 (95% CI 0.54 to 0.71). Addition of phytomedicine to chemotherapy resulted in an increase in the annual cost of treatment by INR 1.241 Billion (US$ 19.64 Million) and prevented 25,217 deaths: the cost-effectiveness of phytomedicine is INR 49,237/death averted (US$ 779/death averted). CONCLUSION: When taken with conventional cancer treatment, phytomedicine shows clinical and cost effectiveness. Domestic manufacturing and practice of phytomedicine should be encouraged. PMID- 26816983 TI - Does Taste Perception Effect Body Mass Index in Preschool Children? AB - INTRODUCTION: Eating trends established early in life leads to chronic life style disorders such as obesity, which is hard to overcome as child comes of age. Energy expenditure is less but caloric intake is high leading to disparity of energy balance in turn leading to obesity. Obesity is the outcome of a disparity between energy expenditure and caloric intake. Genes play a role in establishing eating habits, which is termed as genetic sensitivity to taste. AIM: To determine taste perception effect on body mass index (BMI) in preschool central Indian urban children. MATERIALS AND METHODS: A total of 500 children of 3-6 years were selected and genetic taste perception was assessed using PROP sensitivity test. Anthropometric measurements were recorded to obtain BMI value. Categorical variables were analysed using Pearson's Chi square test. RESULTS: Non tasters were mostly in overweight category i.e. 73.30% where as more number of tasters i.e. 59.70% were in underweight category. A significant correlation is seen between BMI and taste perception. No statistically significant correlation was seen between oral hygiene and taste perception. Females were predominant in both the tasters and non tasters categories. CONCLUSION: Taste perception showed significant relationship with BMI of children between 3-6-year-old children. PMID- 26816984 TI - Effectiveness and Comparison of Various Audio Distraction Aids in Management of Anxious Dental Paediatric Patients. AB - BACKGROUND: Dental anxiety is a widespread phenomenon and a concern for paediatric dentistry. The inability of children to deal with threatening dental stimuli often manifests as behaviour management problems. Nowadays, the use of non-aversive behaviour management techniques is more advocated, which are more acceptable to parents, patients and practitioners. Therefore, this present study was conducted to find out which audio aid was the most effective in the managing anxious children. AIMS AND OBJECTIVES: The aim of the present study was to compare the efficacy of audio-distraction aids in reducing the anxiety of paediatric patients while undergoing various stressful and invasive dental procedures. The objectives were to ascertain whether audio distraction is an effective means of anxiety management and which type of audio aid is the most effective. MATERIALS AND METHODS: A total number of 150 children, aged between 6 to 12 years, randomly selected amongst the patients who came for their first dental check-up, were placed in five groups of 30 each. These groups were the control group, the instrumental music group, the musical nursery rhymes group, the movie songs group and the audio stories group. The control group was treated under normal set-up & audio group listened to various audio presentations during treatment. Each child had four visits. In each visit, after the procedures was completed, the anxiety levels of the children were measured by the Venham's Picture Test (VPT), Venham's Clinical Rating Scale (VCRS) and pulse rate measurement with the help of pulse oximeter. RESULTS: A significant difference was seen between all the groups for the mean pulse rate, with an increase in subsequent visit. However, no significant difference was seen in the VPT & VCRS scores between all the groups. Audio aids in general reduced anxiety in comparison to the control group, and the most significant reduction in anxiety level was observed in the audio stories group. CONCLUSION: The conclusion derived from the present study was that audio distraction was effective in reducing anxiety and audio-stories were the most effective. PMID- 26816985 TI - Fibrinogen Degradation Products and Periodontitis: Deciphering the Connection. AB - INTRODUCTION: Fibrinogen degradation products (e.g. D-dimer) arise from digested fibrin clots and fibrinogen. Elevated concentrations accompany activation of coagulation and fibrinolysis and indicate chronic inflammatory diseases. D-Dimer tests are a quick, noninvasive method to rule out abnormal clotting. Periodontitis strongly affects the haemostatic system and evokes a procoagulant state. Correlation of chronic periodontitis with early indicators of disease (biomarkers) might be useful. AIM: The aim of the study was to examine whether the plasma D-dimer concentration reflects the progression of chronic periodontitis and the beneficial effect of periodontal therapy. MATERIALS AND METHODS: Forty randomly selected subjects were divided into four groups, Group I: 10 healthy subjects, Group II: 10 with mild periodontitis, Group III: 10 with moderate periodontitis, Group IV: 10 with severe periodontitis. After thorough dental and periodontal examination, 3 mL of venous blood was collected for measurement of fibrinogen degradation products. RESULTS: The patients with moderate and chronic periodontitis exhibited high concentrations of D-dimer (mean value 434.98-535.52 mcg/mL), whereas subjects with mild or no periodontitis exhibited values of 329.78-211.29 mcg/mL. Concentrations of D-dimer were significantly reduced after therapy of all classes of periodontitis. CONCLUSION: Periodontal treatment can reduce amount of D-dimer in the plasma. A higher than normal concentration is observed in chronic periodontitis. PMID- 26816986 TI - Association of Temporomandibular Joint Signs & Symptoms with Dental Fluorosis & Skeletal Manifestations in Endemic Fluoride Areas of Dungarpur District, Rajasthan, India. AB - INTRODUCTION: Endemic fluorosis resulting from high fluoride concentration in groundwater is a major public health problem. India is among the numerous nations, where fluoride sullied groundwater is creating wellbeing issues. Safe drinking water in rural areas of India is predominantly rely on groundwater sources, which are exceptionally contaminated with fluoride. AIM: To investigate the association of temporomandibular joint Signs & Symptoms with Dental Fluorosis & Skeletal Manifestations among people living in Dad, Bokersal & Deotalab villages of Dungarpur District, Rajasthan, India. MATERIALS AND METHODS: The study group consisted of 750 subjects who were born & brought up in Dad, Bokersal & Deotalab villages of Dungarpur District, Rajasthan. Temporomandibular joint & Dental fluorosis was assessed by performing type III clinical examination according to WHO guidelines (1997). For the assessment of skeletal manifestations, participants were asked to perform three diagnostic tests: (1)Touching the toes without bending the knees; (2) Touching the chest with the chin; (3) Stretching the arms sideways & folding the arms to touch the back of the head. Chi Square test & Multiple Logistic Regression were applied for statistical analysis. RESULTS: Among the 750 (462 males & 288 females) who participated in the study, 53% had moderate grade of dental fluorosis. The most prominent symptom suggesting Temporomandibular Joint Disorder was the clicking sound affecting 21.4% population.(p>0.001). TMJ Signs & Symptoms were prominent in the age group of 45-54 years & males were highly affected than females. CONCLUSION: Clinical examination of TMJ in Dental Fluorosis & Skeletal Fluorosis subjects showed a significant association with Dental Fluorosis & Skeletal Fluorosis. PMID- 26816987 TI - Morphometry As a Diagnostic Tool for Potentially Malignant Lesions. AB - INTRODUCTION: Though we are in 21(st) century with nano technology & tissue printing, there still exist many lacunae in the field of diagnosis. Not much is known about prognostic markers till now from literature to assess potentially malignant lesions. Lesions so called potentially malignant can be termed only after clinical & malignant changes have been developed and there are no means of predicting with certainty the risk of cancerous transformation. AIM: Our present study was undertaken to establish the morphometric parameters of the parabasal and spinous cells of normal oral epithelium with the changes occurring in cells of Oral Leukoplakia (OL), Oral Verrucous Carcinoma (OVC) and Oral Squamous Cell Carcinoma (OSCC). MATERIALS AND METHODS: Total 40 patients were divided into Group I which includes patients with normal oral mucosa, group II oral leukoplakia patients, group III oral verrucous carcinoma patients and group IV includes oral squamous cell carcinoma patients. Tissue sections were taken and morphometric analysis of cell area, cell diameter, nuclear area, nuclear diameter, nuclear cytoplasmic ratio was done for parabasal and spinous layer cells. Statistical analysis was done using one-way ANOVA and T-test. RESULTS: Nuclear diameter, nuclear area, cell area, nuclear cytoplasmic ratio were significantly increased in OL, OVC, OSCC patients than normal oral mucosa, which was statistically significant. Cell diameter was decreased in OL, OVC, OSCC patients than with normal oral mucosa which was statistically significant. CONCLUSION: Cellular & nuclear parameters showed statistically significant changes in oral leukoplakia, oral verrucous carcinoma & oral squamous cell carcinoma in comparison with normal oral mucosa. PMID- 26816988 TI - Comparative Evaluation of Frictional Properties, Load Deflection Rate and Surface Characteristics of Different Coloured TMA Archwires - An Invitro Study. AB - INTRODUCTION: During tooth movement the success of sliding mechanics is dependent upon various factors which include frictional resistance at bracket-archwire interface, surface roughness of archwire materials and elastic properties of archwires. Ion implantation techniques reduce the frictional force and allow better tooth movement clinically. AIM: The main objective of this study was to evaluate and compare the frictional properties, load deflection rate and surface characteristics of Honey dew and Purple coloured (Ion implanted) TMA wires with uncoated TMA wires. MATERIALS AND METHODS: Fifteen archwire samples were divided into three groups comprising of five samples in each group namely, Group I - Uncoated TMA wires (Control), Group II - Purple coloured TMA wires and Group III- Honey dew TMA wires. Friction and load deflection rate testing were performed with the Instron Universal testing machine and the surface characteristics of the wires were evaluated before and after sliding using Scanning Electron Microscope. RESULTS: The mean frictional characteristics and surface roughness for Honey dew TMA wires was lesser than Purple coloured TMA wires which was statistically significant. Both the coloured TMA wires showed low frictional characteristics and less surface roughness than uncoated TMA wires (the control). The mean load deflection rate was low for both coloured ion implanted TMA wires when compared to uncoated TMA wires which was statistically significant. CONCLUSION: Coloured ion implanted TMA wires, especially Honey dew TMA wires have low friction, low load deflection rate and improved surface finish. Hence they can be used in frictionless as well as sliding mechanics, where uncoated TMA wires are inefficient. PMID- 26816989 TI - Reduction of Complications of Local Anaesthesia in Dental Healthcare Setups by Application of the Six Sigma Methodology: A Statistical Quality Improvement Technique. AB - BACKGROUND: Health care faces challenges due to complications, inefficiencies and other concerns that threaten the safety of patients. AIM: The purpose of his study was to identify causes of complications encountered after administration of local anaesthesia for dental and oral surgical procedures and to reduce the incidence of complications by introduction of six sigma methodology. MATERIALS AND METHODS: DMAIC (Define, Measure, Analyse, Improve and Control) process of Six Sigma was taken into consideration to reduce the incidence of complications encountered after administration of local anaesthesia injections for dental and oral surgical procedures using failure mode and effect analysis. Pareto analysis was taken into consideration to analyse the most recurring complications. Paired z-sample test using Minitab Statistical Inference and Fisher's exact test was used to statistically analyse the obtained data. The p-value <0.05 was considered as significant value. RESULTS: Total 54 systemic and 62 local complications occurred during three months of analyse and measure phase. Syncope, failure of anaesthesia, trismus, auto mordeduras and pain at injection site was found to be most recurring complications. Cumulative defective percentage was 7.99 in case of pre-improved data and decreased to 4.58 in the control phase. Estimate for difference was 0.0341228 and 95% lower bound for difference was 0.0193966. p value was found to be highly significant with p= 0.000. CONCLUSION: The application of six sigma improvement methodology in healthcare tends to deliver consistently better results to the patients as well as hospitals and results in better patient compliance as well as satisfaction. PMID- 26816990 TI - A Comparative Evaluation of the Effectiveness of Three Different Irrigating Solution on Microorganisms in the Root Canal: An Invivo Study. AB - INTRODUCTION: An infected root canal system either due to caries exposure or trauma cannot be eliminated by the host defense mechanisms alone or in combination with systemic antibiotic therapy. It can be treated through professional endodontic intervention using both chemical and mechanical procedures. AIM: To suggest triple antibiotic solution containing tetracycline, ornidazole and ciprofloxacin as a new endodontic irrigant that may possess superior antibacterial activity in comparison with chlorhexidine solution. MATERIALS AND METHODS: This study was carried out on 60 teeth from 40 children with anterior tooth fracture, asymptomatic, non-vital and necrotic in nature. Patients were randomly divided into three groups of 20 teeth each depending upon the type of irrigant. After access opening microbial samples were obtained: a) Pre- irrigation i.e. sample after pulp extirpation and before irrigation, b) Post irrigation i.e. sample after irrigation, stored in sterile containers and immediately transferred to microbiological laboratory. After incubation of samples aerobically at 37(0)C for 24 hours, the samples were streaked on blood agar culture media and incubated for 48 hours. After 48 hours, the colony forming units were counted using a colony counter. Statistical analysis was carried out using Kruskal-Wallis test, Wilcoxson signed rank test and Mann-Whitney test. RESULTS: On intra group comparison, highly significant differences in the colony forming units were found between pre-irrigation and post-irrigation sample for all the three groups. On inter group comparison, statistical difference was found between saline and chlorhexidine (p <= 0.001), saline and triple antibiotic paste (p< 0.001). The greatest percentage decrease was obtained in samples treated with Chlorhexidine solution (Group 2) i.e.73.91. The triple antibiotic irrigating solution group showed percentage decrease of 66.22 followed by Group 1 (Saline) 15.04. The difference found amongst the groups was statistically insignificant. CONCLUSION: It was concluded that triple antibiotic irrigating solution can be used as an irrigating solution. The antibacterial action of triple antibiotic irrigating solution is comparable with chlorhexidine. Although saline may not be effective in the antimicrobial action but its flushing action may be able to decrease some microbial load. PMID- 26816991 TI - Vertical Alveolar Ridge Augmentation by Distraction Osteogenesis. AB - INTRODUCTION: Compromised alveolar ridge in vertical and horizontal dimension is a common finding in patients visiting practitioners for dental prosthesis. Various treatment modalities are available for correction of deficient ridges among which alveolar distraction osteogenesis is one. AIM: To study the efficacy of alveolar distraction osteogenesis in augmentation of alveolar ridges deficient in vertical dimension. MATERIALS AND METHODS: Ten patients aged 16 to 46 years with deficient alveolar ridge underwent ridge augmentation in 11 alveolar segments using the distraction osteogenesis method. For each patient a custom made distraction device was fabricated. The device was indigenously manufactured with SS-316 (ISO 3506). RESULTS: The vertical bone gain reached more than 10mm without the use of bone transplantation. Certain complications like incorrect vector of distraction, paresthesia, pain and loss of transport segment were encountered during the course of the study. CONCLUSION: Alveolar vertical distraction osteogenesis is a reliable and predictable technique for both hard and soft tissue genesis. Implant placement is feasible with primary stability in neogenerated bone at the level of the distracted areas. PMID- 26816992 TI - Evaluation of Crestal Bone Loss Around Implants Placed at Equicrestal and Subcrestal Levels Before Loading: A Prospective Clinical Study. AB - INTRODUCTION: Depth of placement of implant shoulder in relation to the crestal bone positively influence bone remodelling and preservation but the role of placement depth on bone loss before loading is not very clear. AIM: To assess the effect of placement depth alone on the crestal bone loss around implant placed at subcrestal and equicrestal level before prosthetic loading. MATERIALS AND METHODS: Patients reporting to the Department of Prosthodontics with the complaint of missing teeth were enrolled in the study after analysing inclusion and exclusion criteria. A total of 24 implants were planned to be placed into two groups as Group E (n=12) and Group S (n=12). Follow up radiographs after implant placement and after six months were analysed for the amount of bone loss. RESULTS: On six months follow up crestal bone levels of Group E were apical to Group S. Bone loss comparison between groups after six months follow up, revealed almost same mean bone loss. CONCLUSION: The implants placed at subcrestal and equicrestal level did not show difference in crestal bone loss before prosthetic loading. PMID- 26816993 TI - Clinical Evaluation of Neurosensory Changes in the Infraorbital Nerve Following Surgical Management of Zygomatico-Maxillary Complex Fractures. AB - INTRODUCTION: Zygomatico-orbital fractures are the second most common facial injuries. Trauma to mid-facial region can lead to an alteration or loss of sensation in the facial region which sometimes requires early surgical intervention to aid in an early recovery. AIM: To evaluate the different neurosensory changes in the infraorbital nerve function following common treatment modalities used in the management of zygomatico-maxillary complex fractures. MATERIALS AND METHODS: Thirteen patients selected for the study had unilateral zygomatic complex fracture with altered sensation in the region of distribution of the infraorbital nerve. The fractures were managed either by reduction followed by internal fixation with mini-plates (Group A), reduction alone (Group B) or conservatively (Group C). Infraorbital nerve function tests were done by mechanical, heat and pain threshold detection. Evaluation was done on 1(st), 3(rd), 7(th) day, one month, three months and six months interval in a manner similar to that done at the beginning of the study (Day0). RESULTS: A male predominance with male:female ratio of 5.5:1 and an age range of 21 to 50 years was found with the right side mostly affected. Road traffic accident was the most common aetiology. Most common clinical presentations were sub-conjunctival haemorrhage (84.61%), flattening of the malar prominence (69.23%) with deficit in neurosensory function of infra orbital nerve. Recovery in the infraorbital nerve function was relatively complete in 76.92% cases with partial recovery in 23.07% of the patients. CONCLUSION: Marked improvement in the neurosensory function of the infraorbital nerve was found when some form of treatment either in the form of Open Reduction and Internal Fixation (ORIF) or approach through Gillie's temporal or Keen's intraoral approach were applied as compared to when conservative treatment was provided. In zygomatic complex fractures, any form of treatment employed brought about decompression of the infraorbital nerve which aided in the recovery of the nerve within a span of 1-6 months, except when no treatment was applied. PMID- 26816994 TI - The Combined use of Diode LASER & Conscious Sedation in the Excision of Pyogenic Granuloma in A Nine-Year-Old Patient. AB - This case report is to comprehensively review N2O/ O2 inhalational sedation in the context of conscious sedation for treating a nine-year-old patient with pyogenic granuloma. The excision was carried out by the use of diode laser. The six month postoperative follow up showed complete resolution of the lesion and increased patient acceptance for the future treatment. The use of laser minimizes the pain during the surgery and postoperatively and suturing was not required. Therefore this case report emphasizes the use of combined treatment modalities to increase patient comfort and to obtain a better function and aesthetics of the oral cavity. PMID- 26816995 TI - Multiple Compond Odontomas in the Jaws: A Rare Case Report. AB - Odontomas are tumours of odontogenic origin. In these tumours both the epithelial and mesenchymal cells undergo differentiation to form enamel and dentin with variable amounts of cementum and pulp tissue. The odontomas represent a hamartoma rather than a neoplasm. When the enamel and dentin are laid down in an organized manner it is termed as a compound odontoma wherein the tumour forms a collection of small structures resembling teeth. On the other hand, an irregular mass with no similarity to teeth is termed as a complex odontoma. There are cases of extensive and multiple compound odontomas which have been identified in either of the jaws. The present case is rare with multiple compound odontomas involving both the jaws of 45-year-old male patient. A review of seven such cases reported so far has been presented. PMID- 26816996 TI - Unusual Morphological Alteration in Sigmoid Notch: An Insight Through CBCT. AB - The Temporomandibular Joint (TMJ) is a ginglymo-diarthrodial joint known to be the most complex joint in human body. Growth disturbances, owing to genetic influences or trauma during the intrauterine life or during early developmental age may lead to morphological and functional variations in the mandible resulting in developmental anomaly. We report a rare case of altered sigmoid notch morphology on the right side and condylar hypoplasia on the left side, not related to any clear pathological disorder. Cone Beam Computed Tomography (CBCT) was helpful in evaluating this case. This case of unknown aetiology was thoroughly examined; based on clinical and radiographic findings, we suggest that this case is of congenital origin. PMID- 26816997 TI - Abridged Technique for Precise Implant Angulation. AB - Enormous scientific knowledge with evidence and clinical dexterity impart definitive ground for success in implant dentistry. Nevertheless, the unfeasibility to access the inner bone tissue makes the situation altogether more demanding. Presently the advent of numerous imaging techniques and associated surgical guide templates are documented for evaluation of implant angulation. However, they are not cost effective and consume more time to plan and design the structure. This article describes a simple concise technique for precise implant angulation. PMID- 26816998 TI - Concomitant Correction of a Soft-Tissue Fenestration with Keratinised Tissue Augmentation By Using A Rotated Double-Pedicle Flap During Second-Stage Implant Surgery- A Case Report. AB - Soft tissue deficiencies and defects around dental implants have been observed frequently. Soft-tissue defects after implant procedures originate from the process of modelling of periimplant mucosa and often cause aesthetic disharmony, food debris accumulation and soft tissue shrinkage. Periimplant mucogingival surgery focuses on creating an optimum band of keratinized tissue resulting in soft tissue architecture similar to the gingiva around natural teeth. A 23-year old male reported to the Department of Periodontology with a complaint of gum soreness, foul smell and food accumulation at a site where a 3.75 x 11.5mm implant was placed previously. On clinical examination, fenestration of tissue above the cover screw was observed and there appeared to be a keratinized tissue of 1mm surrounding the implant. The case was managed by use of a rotated double pedicle flap during second-stage implant surgery to correct the soft-tissue fenestration defect and to obtain a keratinized periimplant soft tissue. A periosteal bed was prepared by giving a horizontal incision at the mucogingival junction to a depth of 4 mm. Two split-thickness keratinized pedicles were dissected from the mesial and distal interproximal tissues near the implant. After rotation, both the pedicles were sutured to each other mid-buccally and the pedicles were rigidly immobilized with sutures. At 1 month, there was a 3mm band of stable and firm keratinized tissue over the underlying tissues. The procedure resulted in an aesthetic improvement due to enhanced soft tissue architecture and optimum integration between the peri-implant soft tissue and the final prosthesis. PMID- 26816999 TI - Osteoporosis: Its Prosthodontic Considerations - A Review. AB - Osteoporosis is a disease of bone which is common in middle aged post-menopausal women. The osteoporotic bones will become weak and are prone to fractures. Osteoporosis means "porous bone" is a "silent disease". Healthy bone microscopically appears like a honeycomb but, in osteoporotic patients the spaces are much bigger. The osteoporotic bone will have less density or mass and the structure of bone tissue is abnormal. As the bone becomes less dense, they become weaker and more likely to fracture. Women are four times more likely to develop osteoporosis than men. Oral health maintenance for adults with osteoporosis is important. Bone weakness and loss may also affect the ridges that hold dentures resulting in poor fitting dentures. The patients require new dentures more often than those who have strong, healthy bones. Best way to handle problems is avoid delaying or postponing the dental treatment. Regular dental visits and healthy lifestyle is necessary in strengthening and maintenance of good bone health. Well balanced diet with high amounts of vitamin-D & calcium with regular physical activity is recommended. PMID- 26817000 TI - Hirudotherapy in Medicine and Dentistry. AB - The concept of Unani medicine is based on balancing body humours, the imbalance of which causes diseases. The application of leech therapy in medical and dental science is well recognized. Although easy and non-invasive, complications also exist. The article aims to presents a brief review on the applications of leech therapy. The physiological effect, along with its therapeutic role in cancer, diabetes and dentistry have been underlined. Complications of leech therapy have also been dealt with. PMID- 26817001 TI - Effects of Different Concentrations of Fluoride in Oral Mucosal Cells in Albino Rats. AB - INTRODUCTION: Fluoride has been described to be physiologically essential for the normal development and growth of human beings. However, it is well known that excessive fluoride causes skeletal, nonskeletal and dental complications. Therefore, outlining the cytogenetic effects induced by fluorosis is necessary. OBJECTIVES: To evaluate the cytomorphology of exfoliated oral mucosal cells among various concentrations of fluoride. STUDY DESIGN: Study group comprised of 12 Albino Wistar rats, categorized into A,B and C groups (fed with 25 ppm,50 ppm and 100 ppm concentration of NaF), each group consisting of 4 rats, with 4 controls (fed with 1ppm concentration of NaF in distilled water). Each group was fed for a period of 42 days. MATERIALS AND METHODS: Cytological smears were taken from the buccal mucosa of each group after 42 days of fluoride administration. The samples were stained with the papanicolaou method and assessed for Cytomorphometrical changes in maximum diameter of nucleus, minimum diameter of nucleus, perimeter of the nucleus, maximum diameter of the cell, minimum diameter of the cell and perimeter of the cell by image analysis software and the results were statistically analysed using SPSS software. RESULTS: Mean values of maximum diameter, minimum diameter and perimeter of the nucleus increased in fluoride induced study groups when compared to controls and the results showed that p value was statistically significant (p-value: 0.000, 0.001). Mean value of maximum diameter, minimum diameter and perimeter of the cell decreased in fluoride induced subjects when compared with controls which were statistically not significant (p-value: 0.791, 0.600 & 0.719). A continuous increase in the nuclear size and decrease in the cell size was identified in fluoride induced groups as compared to controls. CONCLUSION: The observations of our present study revealed that cellular changes occur with severity of fluorosis. These cellular morphological changes may possibly eventuate into dysplastic alterations, which can progress to malignant changes. PMID- 26817002 TI - Bilateral Fusion of Primary Mandibular Incisors: A Rare Case Report. PMID- 26817003 TI - Energy and Power Density: A Key Factor in Lasers Studies. PMID- 26817004 TI - Endocrine and metabolic emergencies in children: hypocalcemia, hypoglycemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis. AB - It is important to fast diagnosis and management of the pediatric patients of the endocrine metabolic emergencies because the signs and symptoms of these disorders are nonspecific. Delayed diagnosis and treatment may lead to serious consequences of the pediatric patients, for example, cerebral dysfunction leading to coma or death of the patients with hypoglycemia, hypocalcemia, adrenal insufficiency, or diabetic ketoacidosis. The index of suspicion of the endocrine metabolic emergencies should be preceded prior to the starting nonspecific treatment. Importantly, proper diagnosis depends on the collection of blood and urine specimen before nonspecific therapy (intravenous hydration, electrolytes, glucose or calcium injection). At the same time, the taking of precise history and searching for pathognomonic physical findings should be performed. This review was described for fast diagnosis and proper management of hypoglycemic emergencies, hypocalcemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis. PMID- 26817005 TI - Guidelines for genetic skeletal dysplasias for pediatricians. AB - Skeletal dysplasia (SD) is a kind of heterogeneous genetic disorder characterized by abnormal growth, development, differentiation, and maintenance of the bone and cartilage. The patients with SD most likely to be seen by a pediatrician or orthopedic surgeon are those who present with short stature in childhood. Because each category has so many diseases, classification is important to understand SD better. In order to diagnose a SD accurately, clinical and radiographic findings should be evaluated in detail. In addition, genetic diagnosis of SD is important because there are so various SDs with complex phenotypes. To reach an exact diagnosis of SDs, cooperative approach by a clinician, a radiologist and a geneticist is important. This review aims to provide an outline of the diagnostic approach for children with disproportional short stature. PMID- 26817006 TI - Value of serum 1,5-anhydroglucitol measurements in childhood obesity in the continuum of diabetes. AB - PURPOSE: The prevalence of type 2 diabetes mellitus (T2DM) and obesity are currently increasing. Accordingly, the concept of "preventing diabetes" in high risk groups has become more important in diabetic care, but the use of glycated hemoglobin (HbA1c) as a measure has limitations in this field. The aim of this study was to investigate the utility of 1,5-anhydroglucitol (1,5-AG) in assessing prediabetes status in obese children. METHODS: The medical records of 74 subjects aged 6-19 years (of which 27 were overweight/obese and 47 had diabetes) who had 1,5-AG data were reviewed retrospectively. We compared 1,5-AG with HbA1c using the Pearson correlation test to assess the clinical utility of 1,5-AG. RESULTS: 1,5-AG levels were higher (31.1+/-10.1 ug/mL vs. 7.4+/-7.3 ug/mL) and HbA1c levels were lower (5.5%+/-0.3% vs. 8.9%+/-2.7%) in the overweight/obese group than in the diabetics group. The range of 1,5-AG levels in obese children was wide (16.8-59.3 ug/mL), and did not have significance with HbA1c. A negative correlation between 1,5-AG and HbA1c was significant in the entire subject (r= 0.822, P<0.001), and also in the HbA1c range of 5.5% to 8% (r=-0.736, P<0.001). CONCLUSION: 1,5-AG is a valuable index in the HbA1c range of 5.5%-8% and it might be considered an early glycemic control index in insulin-resistant obese children with an HbA1c level above 5.5%. Moreover, the 1,5-AG level assessment should be presented as a supplementary tool for better compliance, as well as being an improvement in diabetes management for the short-term glucose control in relatively well-controlled diabetes patients with an HbA1c level below 8%. PMID- 26817007 TI - Incidence trends and associated factors of diabetes mellitus in Korean children and adolescents: a retrospective cohort study in Busan and Gyeongnam. AB - PURPOSE: This study investigated the incidence trends and associated factors of type 1 (T1DM) and type 2 diabetes mellitus (T2DM) in children and adolescents under 15 years of age in Busan and Gyeongnam, Korea from 2001 to 2010. METHODS: Medical records of newly diagnosed diabetes patients (n=328; 160 males, 168 females) were collected in questionnaire form from 5 tertiary and 42 general hospitals in Busan and Gyeongnam. RESULTS: The average crude incidence rate of T1DM and T2DM was 2.01/100,000 (95% confidence interval [CI], 1.76-2.28) and 0.75/100,000 (95% CI, 0.60-0.92), respectively. The incidence rate ratio (IRR) of T1DM was 1.31 (95% CI, 1.01-1.69), and that of T2DM was 1.97 (95% CI, 1.25-3.11) in the latter half-decade (2006 to 2010) compared to the early half-decade (2001 to 2005). There were gradually increasing incidence trends in both T1DM and T2DM over the 10-year period (P for trend: T1DM, 0.0009; T2DM, <0.0001). Age-specific IRR was highest in the 10- to 14-year-old group, regardless of diabetes type. In particular, a rapid increase in incidence of T2DM occurred in the 10- to 14-year old group. IRR for females was 1.07 (95% CI, 0.83-1.38) for T1DM and 1.56 (95% CI, 1.01-2.41) for T2DM. IRR for Busan (urban) was 1.41 (95% CI, 1.09-1.83) for T1DM and 1.49 (95% CI, 0.96-2.30) for T2DM. CONCLUSION: T1DM and T2DM incidence both increased over time in youth under age 15 living in Busan and Gyeongnam; in particular, the incidence of T2DM in adolescents increased more rapidly. PMID- 26817008 TI - Blood glucose levels within 7 days after birth in preterm infants according to gestational age. AB - PURPOSE: This study investigated blood glucose levels in preterm babies according to gestational age (GA). METHODS: Subjects were 141 preterm infants with a GA<34 weeks. Data on blood glucose levels, GA, body weight, glucose infusion rate, and other contributing factors in the first 7 days after birth were analyzed. Hypoglycemia was defined as a blood glucose level of <40 mg/dL up to 24 hours after birth and as <50 mg/dL thereafter. Hyperglycemia was defined as a blood glucose level >180 mg/dL. RESULTS: During the 7 days after birth, hypo- and hyperglycemia occurred in 29 (29 of 141, 20.6%) and 42 (42 of 141, 29.8%) neonates, respectively. During the first 2 hours, 18 neonates (12.8%) exhibited hypoglycemia, and only 2 (2 of 141, 1.4%) developed hyperglycemia. From 6 to 24 hours, hypo- and hyperglycemia were observed in 0 and 9 (9 of 141, 6.4%) neonates, respectively. Infants small for their GA (SGA) were at risk for hypoglycemia both within 24 hours (odds ratio [OR], 2.718; P=0.045) and during days 2 to 7 (OR, 4.454; P=0.006), and hyperglycemia during days 2 to 7 (OR, 3.200; P=0.005). Low 1-minite Apgar score was risk factor for both hypo- and hyperglycemia during days 2 to 7 (OR, 0.756; P=0.035 for hypoglycemia and OR, 0.789; P=0.016 for hyperglycemia). Both hypo- and hyperglycemia within 24 hours were less common in those who started feeding (OR, 0.294; P=0.013 for hypoglycemia and OR, 0.162; P=0.011 for hyperglycemia). CONCLUSION: Careful blood glucose level monitoring is required in preterm infants, especially SGA infants or those with low Apgar score. Early feeding could be beneficial for maintaining euglycemia. PMID- 26817009 TI - Cerebral salt-wasting syndrome after hematopoietic stem cell transplantation in adolescents: 3 case reports. AB - Cerebral salt-wasting syndrome (CSWS) is a rare disease characterized by a extracellular volume depletion and hyponatremia induced by marked natriuresis. It is mainly reported in patients who experience a central nervous system insult, such as cerebral hemorrhage or encephalitis. The syndrome of inappropriate antidiuretic hormone secretion is a main cause of severe hyponatremia after hematopoietic stem cell transplantation, whereas CSWS is rarely reported. We report 3 patients with childhood acute leukemia who developed CSWS with central nervous system complication after hematopoietic stem cell transplantation. The diagnosis of CSW was made on the basis of severe hyponatremia accompanied by increased urine output with clinical signs of dehydration. All patients showed elevated natriuretic peptide and normal antidiuretic hormone. Aggressive water and sodium replacement treatment was instituted in all 3 patients and 2 of them were effectively recovered, the other one was required to add fludrocortisone administration. PMID- 26817010 TI - Mixed gonadal dysgenesis in 45,X Turner syndrome with SRY gene. AB - Turner syndrome is the most common chromosomal disorder in girls. Various phenotypic features show depending upon karyotype from normal female through ambiguous genitalia to male. Usually, Turner girls containing 45,X/46,XY mosaicism, or sex-determining region Y (SRY) gene may have mixed gonadal dysgenesis with various external sexual differentiation. We experienced a short statured 45,X Turner girl with normal external genitalia. Because SRY gene was positive, laparoscopic gonadectomy was performed. The dysgenetic gonads revealed bilateral ovotesticular tissues. The authors report a mixed gonadal dysgenesis case found in clinical 45,X Turner patient with positive SRY gene. Screening for SRY gene should be done even the karyotype is 45,X monosomy and external genitalia is normal. PMID- 26817011 TI - Pseudohypoaldosteronism in a newborn male with functional polymorphisms in the mineralocorticoid receptor genes. AB - Hyponatremia and hyperkalemia in infancy can be attributed to various causes, originating from a variety of renal and genetic disorders. Pseudohypoaldosteronism type 1 (PHA1) is one of these disorders, causing mineralocorticoid resistance that results in urinary salt wasting, failure to thrive, metabolic acidosis, and dehydration. PHA1 is heterogeneous in etiology. Inactivating mutations in the NR3C2 gene (4q31.1), which encodes the mineralocorticoid receptor, causes a less severe autosomal dominant form that is restricted to the kidney, while mutations in the amiloride-sensitive epithelial sodium channel gene (alpha subunit=SCNN1A, 12p13; beta subunit=SCNN1b, 16p12.2 p12.1; gamma subunit=SCNN1G, 16p12) causes a more severe autosomal recessive form, which has systemic effects. Here we report a neonatal case of kidney restricted PHA1 (renal type of PHA1) who first showed laboratory abnormalities before obvious PHA1 manifestations, with two functional polymorphisms in the NR3C2 gene. This is the second genetically confirmed case in Korea and the first to show functional polymorphisms that have previously been reported in the literature. PMID- 26817012 TI - Turner syndrome with spinal hemorrhage due to vascular malformation. AB - Turner syndrome (TS) is a relatively common chromosomal disorder and is associated with a range of comorbidities involving the cardiovascular system. Vascular abnormalities, in particular, are a common finding in cases of TS. However, dissection involving the vertebral arteries is rare. Here, we report the case of a 9-year-old girl with TS who had been treated with growth hormone replacement therapy for the past 3 years. She presented with weakness of both lower legs, and was ultimately diagnosed with spinal hemorrhage due to vascular malformation. We treated her with intravenous high dose dexamethasone (0.6 mg/kg) and she could walk without assistance after 6 days of treatment. In conclusion, when a patient with TS shows sudden weakness of the lower limbs, we should consider the possibility of spinal vessel rupture and try to take spine magnetic resonance imaging as soon as possible. We suggest a direction how to make a proper diagnosis and management of sudden vertebral artery hemorrhage in patients with TS. PMID- 26817013 TI - Erratum to: Screening newborns for metabolic disorders based on targeted metabolomics using tandem mass spectrometry. AB - [This corrects the article on p. 119 in vol. 20, PMID: 26512346.]. PMID- 26817014 TI - Topical Effect of Glutamine for Colorectal Anastomosis. PMID- 26817015 TI - Efforts to Prevent Surgical Site Infection After Colorectal Surgery. PMID- 26817017 TI - Prognostic Significance of Tissue Leptin Expression in Colorectal Cancer Patients. AB - PURPOSE: Leptin is encoded by the ob gene and is involved in the control of food intake and energy expenditure. Recent studies have implicated leptin expression to be an indicator of tumor features and prognosis. The purpose of this study was to investigate the association of tissue expression of leptin with the clinicopathological characteristics and clinical outcomes in colorectal cancer patients. METHODS: Patients who had undergone a curative surgical resection for a colorectal adenocarcinoma from 2000 to 2004 were included in the study. Immunohistochemical analyses of leptin expression were performed, and clinicopathological parameters were evaluated. RESULTS: Clinical data and tumor tissues of 146 patients were evaluated. The mean age was 68.6 +/- 11.3 years, and 61.0% were men. Immunohistochemically, the rates of negative, weak, moderate, and strong leptin expression were 2.7% (4 of 146), 5.5% (8 of 146), 43.2% (63 of 146), and 48.6% (71 of 146), respectively. We compared the negative, weak, and moderate expression group (group A) with the strong expression group (group B). Leptin expression was inversely associated with nodal stage (P = 0.007) between the two groups. Leptin expression was not significantly associated with differentiation (P = 0.37), T stage (P = 0.16), and American Joint Committee on Cancer stage (P = 0.49), and no significant differences in the disease-free and the overall survivals (P = 0.78 and P = 0.61) were observed. CONCLUSION: Results demonstrated an inverse association of nodal stage with high leptin expression. Higher leptin expression level might predict better oncologic outcome. However, further studies are warranted to identify the exact role of leptin expression in colorectal cancer. PMID- 26817016 TI - Effects of a Glutamine Enema on Anastomotic Healing in an Animal Colon Anastomosis Model. AB - PURPOSE: Anastomotic leakage in colorectal surgery is a very important issue. Although many studies have shown the positive effects of enteral glutamine (Gln) on anastomotic healing, none has assessed the effects of administering Gln via an enema for anastomotic healing. To fill this study gap, this study investigated the intraluminal effect of administration of Gln enema on the healing of colonic anastomosis in a rat model. METHODS: Thirty Wistar albino rats were divided into three groups containing 10 rats each and were subjected to distal left colon transection and anastomosis. Postoperatively, group I (the control group) was administered no treatment, group II was administered daily placebo enemas containing physiological saline, and group III was administered daily 2% L-Gln enemas. After sacrifice on postoperative day 5, anastomotic healing, burst pressure, tissue hydroxyproline levels, and histological parameters were measured, and group values were compared via statistical analysis. RESULTS: Group III was found to have the highest mean bursting pressure and tissue hydroxyproline levels and the lowest mean ischemia score. While the values of these parameters were not found to differ significantly among the groups, the lack of significance may have been due to the limited number of subjects examined. CONCLUSION: Administration of a Gln enema may have a positive effect on anastomosis in terms of bursting pressure and histopathological parameters. Future research should examine administration of a preoperative Gln enema as a means of decreasing the traumatic effects of the enema and identifying its applicability in surgical practice. PMID- 26817018 TI - Age Over 80 is a Possible Risk Factor for Postoperative Morbidity After a Laparoscopic Resection of Colorectal Cancer. AB - PURPOSE: With extended life expectancy, the mean age of patients at the time of diagnosis of colorectal cancer and its treatment, including radical resection, is increasing gradually. We aimed to evaluate the impact of age on postoperative clinical outcomes after a laparoscopic resection of colorectal cancers. METHODS: This is a retrospective review of prospectively collected data. Patients with primary colorectal malignancies or premalignant lesions who underwent laparoscopic colectomies between January 2009 and April 2013 were identified. Patients were divided into 6 groups by age using 70, 75, and 80 years as cutoffs: younger than 70, 70 or older, younger than 75, 75 or older, younger than 80, and 80 or older. Demographics, pathological parameters, and postoperative clinical outcomes, including postoperative morbidity, were compared between the younger and the older age groups. RESULTS: All 578 patients underwent a laparoscopic colorectal resection. The overall postoperative complication rate was 21.1% (n = 122). There were 4 cases of operative mortality (0.7%). Postoperative complication rates were consistently higher in the older groups at all three cutoffs; however, only the comparison with a cutoff at 80 years showed a statistically significant difference between the younger and the older groups. CONCLUSION: Age over 80 is a possible risk factor for postoperative morbidity after a laparoscopic resection of colorectal cancer. PMID- 26817019 TI - Influence of Shorter Duration of Prophylactic Antibiotic Use on the Incidence of Surgical Site Infection Following Colorectal Cancer Surgery. AB - PURPOSE: This study aimed to identify the risk factors for surgical site infections (SSIs) in patients undergoing colorectal cancer surgery and to determine whether significantly different SSI rates existed between the short prophylactic antibiotic use group (within 24 hours) and the long prophylactic antibiotic use group (beyond 24 hours). METHODS: The medical records of 327 patients who underwent colorectal resection due to colorectal cancer from January 2010 to May 2014 at a single center were retrospectively reviewed, and their characteristics as well as the surgical factors known to be risk factors for SSIs, were identified. RESULTS: Among the 327 patients, 45 patients (13.8%) developed SSIs. The patients were divided into two groups according to the duration of antibiotic use: group S (within 24 hours) and group L (beyond 24 hours). Of the 327 patients, 114 (34.9%) were in group S, and 213 (65.1%) were in group L. Twelve patients (10.5%) in group S developed SSIs while 33 patients (15.5%) in group L developed SSIs (P = 0.242). History of diabetes mellitus and lung disease, long operation time, and perioperative transfusion were independent risk factors for SSIs. CONCLUSION: This study shows that discontinuation of prophylactic antibiotics within 24 hours after colorectal surgery has no significant influence on the incidence of SSIs. This study also showed that history of diabetes mellitus and lung disease, long operation time, and perioperative transfusion were associated with increased SSI rates. PMID- 26817020 TI - Pilonidal Abscess Associated With Primary Actinomycosis. AB - Pilonidal disease in the sacrococcygeal region usually presents as abscesses, recurrent inflammation, cellulitis or fistula tracks. However, few reports on actinomycosis affecting pilonidal sinuses have been published. We report a case of a 25-year-old woman who presented with a pilonidal abscess who underwent surgical drainage and debridement. Pus from the pilonidal abscess was sent for microbiology, which grew actinomyces turicensis associated with prevotella bivia and peptostreptococci. She was treated with oral amoxicillin-clavulanate after surgical drainage for one week and recovered well. Actinomycosis associated with pilonidal abscesses, though uncommon, should be recognized and can be satisfactorily treated with a combination of surgical drainage and antibiotics. PMID- 26817021 TI - Necrotizing Fasciitis Arising From an Enterocutaneous Fistula in a Case of an Appendiceal Mucocele. AB - An appendiceal mucocele (AM) is a rare tumorous condition of the appendix. Many patients with AM are admitted to the hospital with abdominal pain or discomfort, and many cases are found incidentally. Although the rate of complications in patients with AM is very low, if left untreated, a mucocele may rupture and produce a potentially fatal entity known as pseudomyxoma peritonei. In this paper, we report a case of an 80-year-old man with necrotizing fasciitis arising from an enterocutaneous fistula caused by AM. PMID- 26817022 TI - Cytomegalovirus Seroprevalence Among Children and Adolescents in Germany: Data From the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), 2003-2006. AB - Background. Congenital cytomegalovirus (CMV) infection can cause severe birth defects. The majority of children with congenital CMV are born to CMV seropositive women; however, transmission from mother to fetus and resulting defects are more likely to occur when mothers experience seroconversion during pregnancy. The objective of this study was to provide a population-based estimate of CMV seropositivity and to identify factors that correlate with the detection of CMV-immunoglobulin (Ig)G antibodies. Methods. Cytomegalovirus-specific IgG antibodies were determined by enzyme-linked immunosorbent assay in 13 876 serum samples from children and adolescents (aged 1-17 years). Cytomegalovirus seroprevalence was correlated with children's age, gender, migration background, country of origin, place of birth, socioeconomic status, breast feeding, daycare attendance, order and number of siblings, and residence in East versus West Germany. Results. Age-adjusted seroprevalence was 27.4% (95% confidence interval, 25.8-29.0). Cytomegalovirus seroprevalence increased with age (21.5% at ages 1-2; 32.0% at ages 14-17). Cytomegalovirus seropositivity was significantly associated with migration background, country of origin and place of birth, and (among migrants only) with low socioeconomic status. Risk factors for CMV acquisition included the birth order of siblings, breastfeeding, early daycare attendance, and living in East Germany. Conclusions. In Germany, CMV seroprevalence increases with age, irrespective of gender. These data highlight risk factors associated with seroprevalence and help to identify a target age for the application of a CMV vaccine. PMID- 26817023 TI - Chronic enzyme replacement therapy ameliorates neuropathology in alpha mannosidosis mice. AB - OBJECTIVE: The lysosomal storage disease alpha-mannosidosis is caused by the deficiency of the lysosomal acid hydrolase alpha-mannosidase (LAMAN) leading to lysosomal accumulation of neutral mannose-linked oligosaccharides throughout the body, including the brain. Clinical findings in alpha-mannosidosis include skeletal malformations, intellectual disabilities and hearing impairment. To date, no curative treatment is available. We previously developed a beneficial enzyme replacement therapy (ERT) regimen for alpha-mannosidase knockout mice, a valid mouse model for the human disease. However, humoral immune responses against the injected recombinant human alpha-mannosidase (rhLAMAN) precluded long term studies and chronic treatment. METHODS: Here, we describe the generation of an immune-tolerant alpha-mannosidosis mouse model that allowed chronic injection of rhLAMAN by transgenic expression of a catalytically inactive variant of human LAMAN in the knockout background. RESULTS: Chronic ERT of rhLAMAN revealed pronounced effects on primary substrate storage throughout the brain, normalization of lysosomal enzyme activities and morphology as well as a decrease in microglia activation. The positive effect of long-term ERT on neuronal lysosomal function was reflected by an improvement of cognitive deficits and exploratory activity. in vivo and in vitro uptake measurements indicate rapid clearance of rhLAMAN from circulation and a broad uptake into different cell types of the nervous system. INTERPRETATION: Our data contribute to the understanding of neurological disorders treatment by demonstrating that lysosomal enzymes such as rhLAMAN can penetrate into the brain and is able to ameliorate neuropathology. PMID- 26817025 TI - Safety and biodistribution assessment of sc-rAAV2.5IL-1Ra administered via intra articular injection in a mono-iodoacetate-induced osteoarthritis rat model. AB - Interleukin-1 (IL-1) plays an important role in the pathophysiology of osteoarthritis (OA), and gene transfer of IL-1 receptor antagonist (IL-1Ra) holds promise for OA treatment. A preclinical safety and biodistribution study evaluated a self-complementary adeno-associated viral vector carrying rat IL-1Ra transgene (sc-rAAV2.5rIL-1Ra) at 5 * 10(8), 5 * 10(9), or 5 * 10(10) vg/knee, or human IL-1Ra transgene (sc-rAAV2.5hIL-1Ra) at 5 * 10(10) vg/knee, in Wistar rats with mono-iodoacetate (MIA)-induced OA at days 7, 26, 91, 180, and 364 following intra-articular injection. The MIA-induced OA lesions were consistent with the published data on this model. The vector genomes persisted in the injected knees for up to a year with only limited vector leakage to systemic circulation and uptake in tissues outside the knee. Low levels of IL-1Ra expression and mitigation of OA lesions were observed in the vector-injected knees, albeit inconsistently. Neutralizing antibodies against the vector capsid developed in a dose-dependent manner, but only the human vector induced a small splenic T-cell immune response to the vector capsid. No local or systemic toxicity attributable to vector administration was identified in the rats as indicated by clinical signs, body weight, feed consumption, clinical pathology, and gross and microscopic pathology through day 364. Taken together, the gene therapy vector demonstrated a favorable safety profile. PMID- 26817026 TI - Editorial: Comorbidities Associated with Orofacial Pain and Headache: A Continuing Emphasis. PMID- 26817024 TI - Merging DBS with viral vector or stem cell implantation: "hybrid" stereotactic surgery as an evolution in the surgical treatment of Parkinson's disease. AB - Parkinson's disease (PD) is a complex neurodegenerative disorder that is currently managed using a broad array of symptom-based strategies. However, targeting its molecular origins represents the potential to discover disease modifying therapies. Deep brain stimulation (DBS), a highly successful treatment modality for PD symptoms, addresses errant electrophysiological signaling pathways in the basal ganglia. In contrast, ongoing clinical trials testing gene and cell replacement therapies propose to protect or restore neuronal-based physiologic dopamine transmission in the striatum. Given promising new platforms to enhance target localization-such as interventional MRI-guided stereotaxy-the opportunity now exists to create hybrid therapies that combine DBS with gene therapy and/or cell implantation. In this mini-review, we discuss approaches used for central nervous system biologic delivery in PD patients in previous trials and propose a new set of strategies based on novel molecular targets. A multifaceted approach, if successful, may not only contribute to our understanding of PD pathology but could introduce a new era of disease modification. PMID- 26817027 TI - Self-Reported Migraine and Chronic Fatigue Syndrome Are More Prevalent in People with Myofascial vs Nonmyofascial Temporomandibular Disorders. AB - AIMS: To compare the number of comorbidities and the prevalence of five specific comorbidities in people who have temporomandibular disorders (TMD) with or without myofascial pain. METHODS: This cross-sectional study included 180 patients seeking TMD treatment in Boston and Montreal hospitals. A self administered questionnaire was used to collect information on sociodemographic and behavioral factors, as well as the presence of the following five comorbidities: migraine, chronic fatigue syndrome, irritable bowel syndrome, interstitial cystitis, and restless leg syndrome. TMD was diagnosed using the Research Diagnostic Criteria for TMD. Chi-square and Student t tests were used for categorical and continuous variables, respectively, to test for differences between myofascial (n = 121) and nonmyofascial (n = 59) TMD groups. Multiple logistic regression analysis was used to compare the type and number of self reported comorbidities in both groups, controlling for confounding variables. RESULTS: The following were found to be significantly higher in the myofascial TMD group than in the nonmyofascial TMD group: self-reported migraine (55% vs 28%, P = .001), chronic fatigue syndrome (19% vs 5%, P = .01), and the mean total number of comorbidities (1.30 vs 0.83, P = .01). CONCLUSION: Individuals with myofascial TMD had a higher prevalence of self-reported migraine and chronic fatigue syndrome than those with nonmyofascial TMD. PMID- 26817028 TI - Explanatory Models of Illness and Treatment Goals in Temporomandibular Disorder Pain Patients Reporting Different Levels of Pain-Related Disability. AB - AIMS: To explore whether temporomandibular disorder (TMD) pain patients reporting different levels of pain-related disability differ in terms of illness explanations and treatment expectations. METHODS: Consecutive TMD pain patients (n = 399; mean +/- SD age, 40.5 +/- 12.7 years; 83% women) seeking treatment in primary care completed the Explanatory Model Scale (EMS). Patients were asked to indicate their expectations regarding the treatment. Each patient's pain-related disability level was determined using the Graded Chronic Pain Scale, with scores indicating no (0 disability points), low (1-2 disability points), or high (3-6 disability points) disability. Differences between EMS factor scores were evaluated using the Mann-Whitney U test. Differences between study groups were analyzed using logistic regression. RESULTS: High-disability patients considered physical and stress factors as more important in causing and in aggravating pain and as targets of treatment compared with patients with no disability (P = .0196 and P = .0251, respectively). The great majority of patients indicated they would like to receive information, decrease pain, and increase jaw function, with no significant subtype differences noted. Compared with no-disability patients, low disability and high-disability patients were more likely to expect increased ability to perform daily functions (P < .0001 in both comparisons), increased work ability (P < .0001 in both comparisons), and better stress management skills (P = .0014 and P = .0001, respectively). CONCLUSION: Illness explanations and goals for treatment differ in patients reporting different levels of TMD pain related disability. PMID- 26817029 TI - Social Context and Dental Pain in Adults of Colombian Ethnic Minority Groups: A Multilevel Cross-Sectional Study. AB - AIMS: To estimate the effect of social context on dental pain in adults of Colombian ethnic minority groups (CEGs). METHODS: Information from 34,843 participants was used. A multilevel model was constructed that had ethnic groups (ie, CEGs and non-CEGs) at level 1 and Colombian states at level 2. Contextual variables included gross domestic product (GDP), Human Development Index (HDI), and Unmet Basic Needs Index (UBNI). RESULTS: Dental pain was observed in 12.3% of 6,440 CEGs. In an unadjusted logistic regression model, dental pain was associated with being a CEG (odds ratio [95% confidence interval], 1.34 [1.22 1.46]; P = .0001). This association remained significant after adjusting for possible confounding variables. An unconditional multilevel analysis showed that the variance in dental pain was statistically significant at the ethnic group level (beta = 0.047 +/- 0.015; P = .0009) and at the state level (beta = 0.038 +/ 0.019; P = .02) and that the variation between ethnic groups was higher than the variation between states (55% vs 45%, respectively). In a multivariate model, the variance in dental pain was also statistically significant at the ethnic group level (beta = 0.029 +/- 0.012; P = .007) and the state level (beta = 0.042 +/- .019; P = .01), but the variation between states was higher (40% vs 60%). The results of multilevel multivariate analyses showed that dental pain was associated with increasing age (beta = 0.009 +/- 0.001; P = .0001), lower education level (beta = 0.302 +/- 0.103; P = .0001), female sex (beta = 0.031 +/- 0.069; P = .003), GDP (beta = 5.136 +/- 2.009; P = .002) and HDI (beta = 6.862 +/ 5.550; P = .004); however, UBNI was not associated with dental pain. CONCLUSION: The variance in dental pain was higher between states than between ethnic groups in the multivariate multilevel model. Dental pain in CEGs was associated with contextual and individual factors. Considering contextual factors, GDP and HDI may play a major role in dental pain prevalence. PMID- 26817030 TI - Inflammatory Cytokines and Sleep Disturbance in Patients with Temporomandibular Disorders. AB - AIMS: To assess the degree and interrelationship of sleep disturbance and plasma cytokine levels in temporomandibular disorder (TMD) pain patients. METHODS: Forty female TMD patients and 20 age-, sex-, and body mass index (BMI)-matched healthy subjects were enrolled. TMD was diagnosed using the Research Diagnostic Criteria for TMD. The TMD patients were classified as having low or high disability according to Graded Chronic Pain Scale findings. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to measure sleep quality. Plasma concentrations of interleukin (IL)-1beta, IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP) were measured from blood samples collected between 9 am and noon. Statistical analyses included Kruskal-Wallis and one-way analysis of variance tests to compare results between different groups and multivariate general linear models to evaluate the effect of sleep status on cytokine levels. RESULTS: The high-disability group had the highest PSQI and ESS scores (P < .001). Plasma levels of IL-1beta, IL-6, IL-10, and TNF-alpha were significantly higher in the patient groups, with the high disability group exhibiting the highest values (P <= .001). The plasma cytokine levels were significantly correlated with PSQI scores (P < .05). Plasma levels of IL-10 and TNF-alpha were significantly associated with the disability level after adjusting for both sleep indices (both P < .05). CONCLUSION: Patients with TMD, especially those with high disability, had elevated plasma cytokine levels and increased ESS and PSQI scores suggestive of sleep disturbance. PMID- 26817031 TI - Prolonged Jaw Opening Promotes Nociception and Enhanced Cytokine Expression. AB - AIMS: To test the hypothesis that prolonged jaw opening, as can occur during routine dental procedures, increases nociceptive sensitivity of the masseter muscle and increases cytokine expression. METHODS: Sprague-Dawley rats were used to investigate behavioral and cellular changes in response to prolonged jaw opening. A surgical retractor was placed around the maxillary and mandibular incisors, and the jaw was held at near maximal opening for 20 minutes. Head withdrawal responses to mechanical stimuli applied to the facial skin overlying the left and right masseter muscles were determined following jaw opening. Cytokine levels in the upper cervical spinal cord containing the caudal part of the spinal trigeminal nucleus were evaluated using protein antibody microarrays (n = 3). Statistical analysis was performed using a nonparametric Mann-Whitney U test. RESULTS: Prolonged jaw opening significantly increased nocifensive head withdrawal to mechanical stimuli at 2 hours, and days 3 and 7 postinduction (P < .05). The increase in nociceptive response resolved after 14 days. Sustained jaw opening also stimulated differential cytokine expression in the trigeminal ganglion and upper cervical spinal cord that persisted 14 days postprocedure (P < .05). CONCLUSION: These findings provide evidence that near maximal jaw opening can lead to activation and prolonged sensitization of trigeminal neurons that results in nociceptive behavior evoked by stimulation of the masseter muscle, a physiologic event often associated with temporomandibular disorders (TMD). Results from this study may provide a plausible explanation for why some patients develop TMD after routine dental procedures that involve prolonged jaw opening. PMID- 26817032 TI - Efficacy of Herpes Simplex Virus Vector Encoding the Human Preproenkephalin Gene for Treatment of Facial Pain in Mice. AB - AIMS: To determine whether herpes simplex virus-based vectors can efficiently transduce mouse trigeminal ganglion (TG) neurons and attenuate preexisting nerve injury-induced whisker pad mechanical hypersensitivity in a trigeminal inflammatory compression (TIC) neuropathic pain model. METHODS: Tissue transduction efficiencies of replication-conditional and replication-defective vectors to mouse whisker pads after topical administration and subcutaneous injection were assessed using quantitative real-time PCR (qPCR). Tissue tropism and transgene expression were assessed using qPCR and reverse-transcriptase qPCR following topical application of the vectors. Whisker pad mechanical sensitivities of TIC-injured mice were determined using graduated von Frey fibers before and after application of human preproenkephalin expressing replication conditional vector (KHPE). Data were analyzed using one-way analysis of variance (ANOVA) and post hoc tests. RESULTS: Transduction of target TGs was 8- to 50-fold greater after topical application than subcutaneous injection and >= 100-fold greater for replication-conditional than replication-defective vectors. Mean KHPE loads remained constant in TGs (4.5-9.8 * 10(4) copies/TG) over 3 weeks but were below quantifiable levels (10 copies/tissue) within 2 weeks of application in other nontarget cephalic tissues examined. Transgene expression in TGs was maximal during 2 weeks after topical application (100-200 cDNA copies/mL) and was below quantifiable levels (1 cDNA copy/mL) in all nontarget tissues. Topical KHPE administration reduced TIC-related mechanical hypersensitivity on whisker pads 4 fold (P < .05) for at least 1 week. CONCLUSION: Topically administered KHPE produced a significant antinociceptive effect in the TIC mouse model of chronic facial neuropathic pain. This is the first report in which a gene therapeutic approach reduced trigeminal pain-related behaviors in an established pain state in mice. PMID- 26817033 TI - Upregulation of the Purinergic Receptor Subtype P2X3 in the Trigeminal Ganglion Is Involved in Orofacial Pain Induced by Occlusal Interference in Rats. AB - AIMS: To evaluate whether the purinergic receptor subtype P2X3 (P2X3R) in trigeminal ganglion (TG) neurons is involved in hyperalgesia of the temporomandibular joints (TMJs) and masseter muscles associated with placement of an occlusal interference. METHODS: Forty-five rats were randomized into five groups (ie, for days 1, 3, 7, 14, or 28; nine rats per group). Six rats from each group were chosen to receive the occlusal interference, and the remaining three rats were sham-treated controls. On days 1, 3, 7, 14, and 28 after placement of the occlusal interference, the mechanical pain threshold (MPT) to stimulation of the TMJs or masseter muscles was examined using von Frey filaments. Seven days after the occlusal interference placement, changes in MPT were tested after administration of the P2X3R antagonist A-317491 into the TMJs and masseter muscles (60 MUg/site) in six rats. The expression of P2X3R in the TGs was investigated by immunohistochemistry and quantitative polymerase chain reaction (qPCR). Retrograde tracing was combined with immunofluorescence to identify TMJ and masseter muscle afferent neurons in the TGs of six premature rats. RESULTS: The TMJ and masseter muscle MPTs were decreased after placement of the occlusal interference, and the P2X3R antagonist reversed the mechanical hyperalgesia that was caused by the occlusal interference placement. The frequency of P2X3R immunoreactive cells increased in small-sized neurons in the TG after occlusal interference. By contrast, there was no increase in medium-sized TG neurons. P2X3R mRNA increased on day 3. Retrograde tracing indicated that the TMJ and masseter muscle afferent neurons in the TG expressed P2X3R. CONCLUSION: Upregulated P2X3R expression in the TG may contribute to orofacial pain development induced by an occlusal interference. P2X3R may be a therapeutic target for chronic TMJ or masseter muscle pain. PMID- 26817034 TI - Coactivation of MU- and kappa-Opioid Receptors May Mediate the Protective Effect of Testosterone on the Development of Temporomandibular Joint Nociception in Male Rats. AB - AIMS: To investigate whether the protective effect of testosterone on the development of temporomandibular joint (TMJ) nociception in male rats is mediated by the activation of central opioid mechanisms. METHODS: Experiments were performed on 156 male Wistar rats. A pharmacologic approach was used to assess the ability of opioid receptor antagonists infused into the dorsal portion of the brainstem and adjacent to the caudal component (subnucleus caudalis) of the spinal trigeminal nucleus to block the protective effect of testosterone in male rats. The TMJ injection of 0.5% formalin was used as a nociceptive stimulus. One way or two-way ANOVA was used for data analyses. RESULTS: The injection of 0.5% formalin into the TMJ induced a significant nociceptive behavior in gonadectomized male rats (P < .05), but not in naive, sham, and testosterone replaced gonadectomized rats, confirming that testosterone prevents the development of TMJ nociception. The injection of either the nonselective opioid receptor antagonist naloxone (15 MUg) or the simultaneous injection of the MU opioid receptor antagonist Cys2, Tyr3, Orn5, Pen7amide (CTOP, 30 MUg) and the kappa-opioid receptor antagonist Nor-Binaltorphimine (Nor-BNI, 90 MUg) significantly increased the 0.5% formalin-induced behavioral response in sham and testosterone-replaced gonadectomized rats (P < .05) but had no effect in gonadectomized rats. However, the injection of each selective opioid receptor antagonist alone or the simultaneous injection of MU- or kappa- and delta-opioid receptor antagonists had no effect. CONCLUSION: These findings indicate that the protective effect of endogenous testosterone on the development of TMJ nociception in male rats is mediated by the activation of central opioid mechanisms. Furthermore, the coactivation of central MU- and kappa-opioid receptors is necessary for testosterone to protect male rats from developing TMJ nociception. PMID- 26817035 TI - Short-Lasting Unilateral Neuralgiform Headache with Conjunctival Injection and Tearing Secondary to Head and Neck Trauma: Literature Review and Case Report. AB - This article reports a case of secondary short-lasting unilateral neuralgiform headache with conjunctival injection and tearing following head and neck trauma due to a violent assault. Following the incident, the patient began experiencing 4 to 30 shooting/sharp pain attacks per day in the left anterior temporal and supraorbital areas, with an intensity of 10/10 on a numeric rating scale. Each attack lasted between 10 and 60 seconds. These attacks were accompanied by ipsilateral conjunctival injection, tearing, ptosis of the left eye, blurry vision, and occasional rhinorrhea. Significant improvements in sleep, autonomic symptoms, and pain were observed with a combination of melatonin 10 mg per day, gabapentin 300 mg twice daily, physical therapy, and psychotherapy. This case highlights the relevance of a multidisciplinary approach in the treatment of challenging cases when there is evidence of more than one contributing factor, with the aim of reducing pain and improving the patient's quality of life. PMID- 26817036 TI - Editorial: Oral Health for a Better Life. PMID- 26817037 TI - Dissecting the thorax. PMID- 26817038 TI - Complementary medicines. PMID- 26817039 TI - Reply. PMID- 26817040 TI - Removing the "Silencer": Coverage and Protection of Physician Speech Under the First Amendment. AB - The physician-patient relationship rests on a bedrock of trust. Without trust, patients--and for that matter, physicians--are less willing to divulge information critical to providing accurate medical diagnoses and treatments. The state of Florida seemingly ignored this when its legislature, with support from the National Rifle Association and other pro-gun advocates, enacted the Firearm Owners Privacy Act (FOPA), a statute that restricts physicians from questioning their patients about firearm ownership. In Wollschlaeger v. Governor of Florida, the United States Court of Appeals for the Eleventh Circuit held that FOPA did not regulate physician speech but, instead, regulated physician conduct. As such, the law was exempted from First Amendment scrutiny. But almost one year to the day after publishing its first Wollschlaeger opinion, the Eleventh Circuit sua sponte vacated its original opinion and substituted in its place a brand new opinion--one holding that FOPA was subject to First Amendment scrutiny, but nonetheless passed constitutional muster. This Note uses the diverging Wollschlaeger opinions as a vehicle to analyze the First Amendment's coverage and protection of physician speech. Specifically, it argues that an uninhibited line of communication is required to protect the trust necessary for an effective physician-patient relationship. This logical underpinning leads to the conclusion that the First Amendment presumptively covers physician speech and, furthermore, that physician speech should be subject to intermediate scrutiny--a level of scrutiny that FOPA cannot meet. PMID- 26817041 TI - Letters to the Editor. PMID- 26817042 TI - Don't Throw Me Under the Bus. PMID- 26817043 TI - "How Dentists Rip Us Off". PMID- 26817044 TI - Ethics: What Do We Have to Lose? PMID- 26817045 TI - It's on Facebook, So It Must Be True. PMID- 26817046 TI - What To Do With Dick and Jane. PMID- 26817047 TI - Dentists with Substance use Disorders: HELP is Available. PMID- 26817048 TI - HIP 2.0: Plan Limitations Lead to Ethical Dilemmas. PMID- 26817049 TI - Using Prescriptive Supervision in Your Dental Practice. PMID- 26817050 TI - The Care and Keeping of Patient Records. PMID- 26817051 TI - Run With Your Heart, Not With Your Legs. PMID- 26817052 TI - Bond, Dr. James Bond? PMID- 26817053 TI - [Mass Spectrometry Based Metabolic Study; Application to Mitochondria Dysfunction Model for Biomarker Discovery]. PMID- 26817054 TI - [Strategy of Surgical Treatment for Pancreatic Cancer]. PMID- 26817055 TI - [A Case of Laparoscopic Surgery for Early Gastric Cancer that Occurred after Coronary Artery Bypass Grafting using the Right Gastroepiploic Artery]. AB - We herein report a case involving a 70-year-old man who was diagnosed with early gastric cancer that occurred after coronary artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA) for effort-induced angina. He was successfully treated by laparoscopic surgery. Preoperative cardiac three dimensional computed tomography and coronary angiography showed an occlusion of the RGEA graft, which could lead to ligation of the RGEA to dissect the lymph nodes along the RGEA. The laparoscopic approach helps to identify and avoid injury to the RGEA graft because of its enlarged and precise viewing field compared with laparotomy followed by retractor placement. Laparoscopic surgery is a useful method in such cases to reduce perioperative complications risk. PMID- 26817057 TI - PRESIDENT'S PAGE. PMID- 26817056 TI - Up in Smoke.... PMID- 26817058 TI - A Brief History of the Tobacco Settlement in Oklahoma. PMID- 26817059 TI - Tobacco Control and Prevention in Oklahoma: Best Practices in a Preemptive State. AB - For more than a decade, the Oklahoma Tobacco Settlement Endowment Trust and Oklahoma State Department of Health have collaborated to implement best practices in tobacco control through state and community interventions, including legislated and voluntary policy approaches, health communication, cessation programs, and surveillance and evaluation activities. This partnership eliminates duplication and ensures efficient use of public health dollars for a comprehensive tobacco control program based on a systems and social norm change approach. The purpose of this paper is to briefly describe strategies to reduce tobacco use despite a rare policy environment imposed by the presence of near complete state preemption of tobacco-related law. Key outcome indicators were used to track progress related to state tobacco control and prevention programs. Data sources included cigarette excise tax stamp sales, statewide surveillance systems, Oklahoma Tobacco Helpline registration data, and local policy tracking databases. Data were collected in 2001-2013 and analyzed in 2012 and 2013. Significant declines in cigarette consumption and adult smoking prevalence occurred in 2001-2012, and smoking among high school students fell 45%. Changes were also observed in attitudes and behaviors related to secondhand smoke. Community coalitions promoted adoption of local policies where allowable, with 92 ordinances mirroring state clean indoor air laws and 88 ordinances mirroring state youth access laws. Tobacco-free property policies were adopted by 292 school districts and 309 worksites. Moving forward, tobacco use will be prioritized as an avoidable health hazard in Oklahoma as it is integrated into a wellness approach that also targets obesity reduction. PMID- 26817060 TI - Tobacco Industry Influences in the Oklahoma Legislature. AB - OBJECTIVE: To identify recent tobacco industry influences in the Oklahoma Legislature. METHODS: Relevant public records were compiled and published online in searchable databases. Activities related to two contested tobacco-related legislative initiatives were analyzed. Analyses of voting behavior controlled for party affiliation. RESULTS: Legislators receiving the largest amounts of campaign contributions and gifts from tobacco lobbyists performed actions necessary to advance tobacco industry objectives. Several significant associations with voting behavior were observed, the strongest of which was between votes on a pro-tobacco industry bill and gifts from tobacco lobbyists. Most lobbyists'gifts were meals. CONCLUSIONS: Tobacco industry influence in the Oklahoma Legislature is enhanced through tobacco lobbyists' campaign contributions and gifts. Greater investments are made in legislative leaders, those serving as champions or spokespersons, and others taking key roles in advancing tobacco industry objectives. Exposing such influences may diminish their effects. Given the egregious and uniquely destructive behavior of the tobacco industry, lawmakers could, as an ethical matter of principle, refuse tobacco lobbyists' money and seek to remedy past harms. PMID- 26817061 TI - Oklahoma "Tobacco Stops with Me"Media Campaign Effects on Attitudes toward Secondhand Smoke. AB - IMPORTANCE: Public education campaigns in tobacco control play an important role in changing tobacco-related knowledge, attitudes and behaviors. The Oklahoma Tobacco Stops with Me campaign has been effective in changing attitudes overall and across subpopulations towards secondhand smoke risks. OBJECTIVE: Investigate campaign impact on secondhand smoke policy and risk attitudes. DESIGN: Serial cross-sectional data analyzed with univariate and multivariable models. SETTING: Random-digit dialing surveys conducted in 2007 and 2015. PARTICIPANTS: Oklahomans 18-65 years old. MAIN OUTCOMES AND MEASURES: 1) Support for smokefree bars; 2) risk assessment of secondhand smoke (very harmful, causes heart disease, causes sudden infant death); and 3) likelihood of protecting yourself from secondhand smoke. RESULTS: With Tobacco Stops with Me exposure, from 2007 to 2015, Oklahomans demonstrated significant increases in: 1) supporting smokefree bars (23.7% to 55%); 2) reporting beliefs that SHS causes heart disease (58.5% to 72.6%), is very harmful (63.8% to 70.6%) and causes sudden infant death (24% to 34%); and 3) reporting they are very likely to ask someone not to smoke nearby (45% to 52%). Controlling for demographics, smokers and males showed reduced attitude change. In uncontrolled comparisons, high-school graduates faired better than non-diploma individuals, who lacked significant attitude changes. CONCLUSIONS AND RELEVANCE: Tobacco Stops with Me achieved its mission to more closely align public perception of SHS with well-documented secondhand smoke risks. Efforts to target women were particularly successful. Smokers may be resistant to messaging; closing taglines that reinstate individual choice may help to reduce resistance/reactance (e.g., adding Oklahoma Helpline contact information). PMID- 26817062 TI - State-Level Correlates of Unassisted Quit Attempts and Success. AB - BACKGROUND: Although the majority of smokers attempting to quit do so without assistance, research in the area of unassisted quit behaviors is limited. The aim of this study was to investigate whether population-level policies and programs, such as smoke-free air policies and tobacco control programs, contribute to unassisted quit attempts and cessation. METHODS: The current study used the 2003 Tobacco Use Supplement to the Current Population Survey (TUS-CPS) special Cessation Supplement (CS) to estimate unassisted quit attempt and success rates by state. Linear regression was used to examine whether state-level unassisted quit attempt and success rates were related to state-level policies and social norms. State-level factors investigated were tobacco control program funding, tobacco taxes, smoke-free air policies, state anti-smoking sentiment and recent change in smoking prevalence. RESULTS: Consistent with previous studies, this study found the majority of smokers who attempted to quit did so without assistance. This study also found unassisted quit attempt rates were higher than assisted attempt rates in every state and DC. Additionally, unassisted quit success rates were higher than assisted quit success rates in most states; however, some states had higher assisted quit success rates. State-level factors associated with unassisted quit attempt rates included anti-smoking sentiment and tobacco taxes; however, no significant relationships were uncovered between unassisted quit success rates and state-level factors. CONCLUSIONS: These results suggest that state-level factors may be more important in motivating smokers to attempt quitting, and other individual factors or unmeasured state factors may be related to quit success. PMID- 26817063 TI - Economic Impact of Oklahoma's Smoke-Free Air Policies on Restaurants. AB - A comparison of sales tax and employment data from before and after the new statewide secondhand smoke laws took effect on March 1, 2006, finds that both revenue and employment levels have increased for Oklahoma restaurants since imposition of the new rules. Furthermore, comparing revenue and employment levels across states, with Kansas, and controlling for changes in overall economic activity, shows that Oklahoma has done relatively better than Kansas, since imposition of the new law. Kansas had no similar change to its restaurant smoking rules, which still largely permitted smoking, during the study timeframe. PMID- 26817064 TI - Increased Evidence-Based Tobacco Treatment Through Oklahoma Hospital System Changes. AB - BACKGROUND: Oklahoma hospitals admit approximately 120,000 tobacco users each year, many for diseases resulting from tobacco use. PURPOSE: To describe a unique partnership between the Oklahoma Hospital Association and Oklahoma Tobacco Settlement Endowment Trust to reach more tobacco users through the implementation of sustainable health system changes within hospitals and clinics to integrate an evidence-based tobacco treatment protocol for all tobacco-using patients. METHODS: The Oklahoma Hospital Association tobacco-cessation model included (1) identifying all tobacco-using patients; (2) assessing addiction level and readiness to quit; (3) prescribing medications to manage withdrawal while in hospital; and (4) proactively faxing a referral to the Oklahoma Tobacco Helpline for all patients ready to quit. Helpline registration patterns and characteristics of fax-referred hospitalized patients were tracked for the 4 years of the initiative (2009-2013); data were analyzed in 2013. RESULTS: Twenty one hospitals and 12 clinics participated in the initiative. Fax referrals to the Helpline increased by > 150% in the first year, from about 600 during the year prior to the implementation of the program (July 2009 to June 2010) to 1,581 from Oklahoma Hospital Association facilities alone in the first year following the launch of the initiative. Nearly 5,600 Oklahoma Hospital Association fax referrals were made during the 4-year study period. About 41% of these referrals resulted in Helpline enrollment (n = 2,289). CONCLUSIONS: Sustainable, evidence based tobacco treatment interventions embedded in hospital systems can successfully identify tobacco users and provide effective treatment, including increased proactive Helpline referrals for quit coaching. PMID- 26817065 TI - Factors Associated With Smoking Cessation Attempts in Asthmatics. AB - Asthma is a common disorder affecting about 8% of adults in the U.S. Smoking is one factor that is associated with exacerbations of the disease. Somewhat surprisingly, the smoking prevalence among asthmatics is about the same as for the general population. It would be helpful to understand the demographic characteristics associated with those asthmatics who are smokers and who attempt to quit in order to better design approaches to help with cessation. This study examined the data from the 2012 Behavior Risk Factor Surveillance System (BRFSS) Asthma Call-Back Survey (ACBS), specifically demographic data such as gender, education, race/ethnicity, employment and others, to see if there are common characteristics in those asthmatics who attempt smoking cessation. We found that the only two statistically significant demographic characteristics were education and race. However, about two-thirds of those who made an attempt had had an episode of asthma in the past year and were more likely to have sought emergency care for asthma. These findings may help design better programs to help those patients with asthma who smoke. PMID- 26817066 TI - Race and Gender Disparities in Lung Cancer Incidence Rates, 2001-2010. AB - OBJECTIVE: Despite progress to reduce the burden of tobacco, disparities in tobacco-related morbidity and mortality remain. This research examines trends in lung cancer incidence rates by race and by gender within race during 2001-2010 in Oklahoma. METHODS: Incident cases of lung cancer were obtained from the Oklahoma State Department of Health public use database. Cases were linked to the Indian Health Service database to reduce misclassification of American Indian race. Annual percent change (APC) was estimated by race and by gender within race to describe rates over time. Rates were considered to increase or decrease if the p value for trend was < 0.05. RESULTS: Average lung cancer incidence rates were highest among American Indians (105.52 per 100,000) and lowest among whites (78.64 per 100,000). Lung cancer incidence rates declined among the overall white (APC: -2.17%; p = 0.001) and African American (APC: -2.95%; p = 0.003) populations, as well as white (APC: -3.02%; p < .001) and African American males (APC: -3.39%; p = 0.007). Rates increased among American Indian females (APC: 2.20%; p = 0.03). CONCLUSION: Analysis of lung cancer incidence data reveals an inequality in tobacco-related morbidity among American Indians, especially American Indian females. This research suggests a need for more evidence-based tobacco control interventions within the American Indian population. PMID- 26817067 TI - An Ecological Analysis of Tobacco Use and Oral Cavity and Pharynx Cancers in U.S. Males. AB - BACKGROUND: As the 8th most frequently diagnosed cancers among U.S. males, cancers of the oral cavity and pharynx are a significant component of the cancer burden among U.S. males. Avoidance of tobacco products is critical for the prevention of oral cavity and pharynx cancers. The objective of this brief report was to describe state-specific incidence rates of oral cavity and pharynx cancers and to examine the correlation between state-specific prevalences of tobacco use and oral cavity and pharynx cancer incidence rates among U.S. adult males. METHODS: Secondary surveillance data were used to conduct this ecological analysis. Incidence rates of oral cavity and pharynx cancers during 2009 through 2011 among males were obtained from the Centers for Disease Control and Prevention (CDC) WONDER system. Prevalences of cigarette smoking and smokeless tobacco use during 1995 and 1996 among males were obtained from the CDC STATE System. Relations were examined by calculating Pearson correlation coefficients and by performing linear regression analysis. Statistical significance was considered at alpha < 0.05. RESULTS: Current cigarette smoking prevalence was significantly correlated (r = 0.57; r2 = 0.33; p-value = < .0001) with the incidence rate of oral cavity and pharynx cancer; while there was a non statistically significant correlation (r = 0.22; r2 = 0.05; p-value = 0.1147) between smokeless tobacco use and oral cavity and pharynx cancer. A 1% increase in the prevalence of current cigarette smoking was estimated to increase the incidence rate of oral cavity and pharynx cancer by 0.52 per 100,000 males. Although non-statistically significant, a 1% increase in the prevalence of smokeless tobacco use was estimated to increase the incidence rate of oral cavity and pharynx cancer by 0.18 per 100,000 males. CONCLUSION: Among U.S. males, a statistically significant positive correlation was observed between cigarette smoking and oral cancer, but not between smokeless tobacco use and oral cancer. Moreover, current cigarette smoking was estimated to predict one-third of the total variability in oral cancer. These findings contribute to the body of literature and provide further evidence that cigarette smoking is an important behavioral risk factor for oral cavity and pharynx cancer among U.S. males. PMID- 26817068 TI - Barriers And Motivators for Smoking Cessation in Patients With Systemic Lupus Erythematosus (SLE). AB - Although studies have shown that smoking is detrimental to the health of patients with systemic lupus erythematosus (SLE), studies regarding barriers and motivators for smoking cessation are lacking. The purpose of this study was to generate hypotheses regarding the barriers and motivators for smoking cessation in SLE patients. METHODS: This study was based on the theoretical framework of the stages of change model. All participants met SLE classification criteria. Interviews were conducted with 16 current and 10 former smokers. RESULTS: Motivators included: medical reasons, readiness, and concern for others. Barriers included: enjoyment, coping mechanism, and an emotional connection. Participants were unsure of the impact of smoking on their medication and disease, and had mixed feelings regarding the impact on pain. CONCLUSION: The main motivator for cessation in this population was concern for one's health. Rheumatologists need to include disease specific harms and assess pain management strategies as part of cessation counseling. PMID- 26817069 TI - Detection of In Vivo DNA Damage Induced by Very Low Doses of Mainstream and Sidestream Smoke Extracts Using a Novel Assay. AB - BACKGROUND: Mainstream (MS) smoke, the main smoke inhaled by active smokers, and sidestream (SS) smoke, the main component of secondhand smoke, induce a wide range of DNA lesions. Owing to technical limitations, the in vivo levels of tobacco-induced DNA damage are unknown. Recently, the authors developed a highly sensitive primer-anchored DNA damage detection assay (PADDA) to quantify endogenous and induced DNA damage. PURPOSE: To quantify the in vivo levels of DNA damage induced by MS and SS smoke extracts in human cells using PADDA and define the strand-specific patterns of DNA damage and repair following exposure to diverse doses of MS and SS smoke. METHODS: Human epithelial cells were exposed to escalating doses of hydrogen peroxide (H2O2), MS; or SS smoke. TP53 gene DNA damage was quantified using PADDA at various time points. DNA double-strand breaks were detected by immunofluorescence analysis of phosphorylated histone H2AX (gamma-H2AX). Cell viability was determined by 3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide (MTT) assay. Data were collected and analyzed by t-test in 2012-2014. RESULTS: A dose-dependent increase in DNA damage was detected in vivo with increasing doses of H2O2, MS, and SS smoke. Even 1 hour of exposure to very low doses of MS or SS smoke resulted in significant DNA damage (p < 0.01). MS and SS smoke induced distinctive strand-specific patterns of DNA damage and DNA repair kinetics. CONCLUSIONS: Very low concentrations of MS and SS smoke induce significant DNA damage in human cells. Application of PADDA to population studies has major potential to establish biomarkers of susceptibility to tobacco-induced diseases. PMID- 26817070 TI - Patient Pages. TOBACCO STOPS WITH ME. FACTS & STATS. PMID- 26817071 TI - Patient Pages. TOBACCO STOPS WITH ME. SECONDHAND SMOKE. PMID- 26817073 TI - GUIDE TO QUITTING SMOKING. PMID- 26817072 TI - Patient Pages. HEALTH RISKS OF SMOKELESS TOBACCO. PMID- 26817074 TI - [REOPERATIONS IN PATIENTS, SUFFERING CYSTIC TRANSFORMATION OF COMMON BILIARY DUCT]. AB - Own experience of treatment of the common biliary duct cysts was analyzed in the patients, to whom earlier noneffective operative procedures for this purpose were performed. The main causes of the operations faults were unmasked, the proposed treatment-diagnostic algorithm was proposed, immediate and remote results of operative treatment were analyzed. PMID- 26817075 TI - [ENDOSCOPIC DIAGNOSIS AND TREATMENT OF INJURIES OF BILIARY DUCTS IN LAPAROSCOPIC OPERATIONS]. AB - The results of endoscopic diagnosis and treatment of 127 patients for iatrogenic injuries of biliary ducts while laparoscopic cholecystectomy performance are adduced. Taking into account a necessity to follow principles of miniinvasiveness while performing laparoscopic cholecystectomy, it is expedient to apply miniinvasive methods for elimination of its possible complications as well. In presence of clinical signs of an acute abdomen, free liquid in abdominal cavity (in accordance to ultrasonographic investigation data), application of endoscopic methods of diagnosis and treatment of the biliary ducts iatrogenic injuries is not indicated. Rational application of miniinvasive (endoscopic and under ultrasonographic control) interventions have permitted in all the patients to achieve closure of a partly external biliary fistulas and to sanate intraabdominal foci of biliary accumulations. PMID- 26817076 TI - [THE TREATMENT OF POSTOPERATIVE STRICTURE OF BILIARY DUCTS: A 15-YEARS EXPERIENCE AND OBSERVATIONS FROM THE PRACTICE]. AB - Experience of performance of 160 operations for injuries and stricture of biliary ducts, was analyzed. In 36 patients before admittance to hospital there were performed interventions, which provide correction of injuries or their consequences. In majority (141) of patients hepaticojejunoanastomosis in accordance to Roux method or its reconstruction were performed. Other interventions (right-sided hemihepatectomy) were rarely performed. The procedure of anastomosis formation, permitting to connect the mucosae of joining organs in precision, was proposed. Clinical observations of correction of the biliary ducts stricture were presented. PMID- 26817077 TI - [PROGNOSTIC SIGNIFICANCE OF ELEMENTS OF THE MULTIORGAN INSUFFICIENCY SYNDROME AND ESTIMATION OF THE PATIENTS STATE SEVERITY IN ACCORDANCE TO INTEGRAL SCALES IN AN ACUTE NECROTIC PANCREATITIS]. AB - There were examined 113 patients, in whom an acute necrotic pancreatitis was diagnosed. While admittance to hospital a constant organ insufficiency was revealed in 50 (44%), a transient one--in 63 (56%) patients. In total 31 (27.4%) patients died. Respiratory insufficiency have occurred in 67% patients, and almost with similar rate--cardio-vascular (in 59%), renal (in 56%) and enteral (in 54%), dominating in the lethality structure. The BISAP (Bedcide Index for Severity in Acute Pancreatitis) scales applied permit with high probability to prognosticate the organ insufficiency and lethality in patients, suffering an acute necrotic pancreatitis. PMID- 26817078 TI - [SURGICAL TREATMENT OF POSTOPERATIVE STRICTURE OF ANAL CHANNELL]. AB - The results of treatment of 50 patients, suffering postoperative stricture of anal channell (SACH), who were treated in Proctology Department of Ivano Frankivskiy Rural Clinical Hospital in 2006-2014 yrs, were analyzed. After conduction of hemorrhoidectomy in accordance to Milligan-Morgan method for chronic hemorrhoids grades III-IV a SACH have occurred in 46 (92%) patients, excision of a chronic anal fissura was performed in 3 (6%) and excision of perianal pointed condylomas--in 1 patient. In 2006-2007 yrs 11 (22%) patients were operated in accordance to approaches, which were conventional at that time (comparison group). In 2008 - 2014 yrs 39 (78%) patients were admitted to hospital (main group), in whom new approaches for diagnosis, conservative and surgical treatment were applied, 30 (76.9%) of them were operated. The proposed method on isolated roentgen contrast investigation of anal channell have permitted to determine objectively a form, diameter and grade of the anal channel stricture, and it may be applied as a screening procedure, as additional objective criterion while choosing a surgical tactic. Application of the improved operative technique for SACH have permitted to lower its occurrence rate from 45.4 to 6.7%. PMID- 26817079 TI - [THE RISK FACTORS OF THE DIALYSIS PERITONITIS (THREE-YEARS PROSPECTIVE INVESTIGATION)]. AB - The risk factors of the dialysis peritonitis occurrence were determined in patients with chronic renal disease, to whom a substitute renal therapy, using peritoneal dialysis, was conducted. The results of a three-year prospective investigation and treatment of 73 patients in Kyiv City Oleksandrivska Clinical Hospital on the base of the general surgery and nephrology departments in 2007 - 2010 yrs were studied. The dialysis peritonitis (first episode) have occurred in 42 (57.5%) patients. Cumulative rate of a dialysis peritonitis in accordance to a censored data (the dialysis peritonitis suspension or other causes) have constituted 67.7%. Due to the dialysis peritonitis occurrence the peritoneal dialysis was stopped in 14 (19.2%) patients. The obesity, raising of a serum albumin level, constipation, preliminary injection into the site of the catheter exit site we consider a risk factors for the dialysis peritonitis occurrence. PMID- 26817080 TI - [ANALYSIS OF THE INTRAOPERATIVE PROPHYLAXIS EFFICACY OF THE ABDOMINAL CAVITY ADHESIVE DISEASE]. AB - Results of treatment of 152 patients, operated on for various diseases of the abdominal cavity, were analyzed. In 72 of them (the main group) intraoperatively a Defensal was used as an antiadhesive barrier preparation for the abdominal adhesions prophylaxis, and in 80 (a comparison group)--antiadhesive measures were not conducted. Application of antiadhesive sterile solution have promoted a reduction of period, which is necessary for the gut motor-evacuation function restoration--by 1.5 days, stationary treatment--by 2.5 days, postoperative morbidity rate--in 2.7 times. PMID- 26817081 TI - [FIRST EXPERIENCE OF APPLICATION OF TECHNOLOGY OF A TWO-STREAM LOW-FREQUENCY ULTRASOUND TECHNOLOGY IN ABDOMINAL SURGERY]. AB - Biophysical peculiarities of action on tissues of a two-strem low-frequency ultrasound (TSLFU) technology, elaborated by "Arobella Medical LLC" (USA) firm, were studied. Capacity of ultrasound to separate a pathologically-changed and healthy tissues, to divide the structures in accordance to their bioacoustical parameters constitutes the technology peculiarities. The presence of such a biophysical effect permits to achieve high resectability (R0) in patients with oncological diseases. Antibacterial effect and stimulation of intraorgan microcirculation with ultrasound irradiation were noted. Biophysical peculiarities of TSLFU were successfully applied in surgical treatment of 48 patients, suffering inflammatory and oncological diseases of the abdominal cavity organs. PMID- 26817082 TI - [DIAGNOSTIC ESTIMATE OF A C-REACTIVE PROTEIN IN DIFFERENTIAL DIAGNOSIS OF SEPSIS AND SYNDROME OF SYSTEMIC INFLAMMATORY ANSWER]. AB - Expedience of determination of a C-reactive protein contents in the early diagnosis of septic complications in children with surgical and somatic pathologies, admitted to hospital, in severe state into departments of reanimatology and intensive therapy, were studied up. PMID- 26817083 TI - [PLASTY OF THE INTERVENTRICLE SEPTUM DEFECT, USING A PATCH WITH A VALVE IN PATIENTS, SUFFERING HIGH PULMONARY ARTERIAL HYPERTENSION AND ENHANCED RESISTANCE OF PULMONARY ARTERIES]. AB - Right ventricle insufficiency due to pulmonary hypertensive crysis or persisting pulmonary arterial hypertension (PAH) in patients after the interventricle septum defect (IVSD) closure with the heightened resistance of pulmonary arteries (RPA) constitutes an actual problem and associates with a high risk for a life threatening complications and high lethality. Experience of the IVSD plasty conduction in a patient with high PAH, using a patch with a valve for right ventricle decompression while pulmonary hypertensive crysis in early postoperative period and nonreversible PAH in the remote period of observation, was presented. In the clinic 38 children were operated on for big IVSD, complicated by high PAH and heightened RPA, using a patch with a valve in 1996 - 2014 yrs. Hospital lethality have constituted 2.6%. Postoperatively a pressure in pulmonary artery (PA) have lowered trustworthy from (93.4 ? 14.9) to (49.2 ? 22.9) mm Hg. In a remote period of observation all the patients were alive. In 6 (16.2%) patients in terms from 4 mo to 18 yrs postoperatively a PAH have occurred, a pressure in PA was by 50% higher, than a systemic one. The IVSD plasty in patients with high PAH and heightened RPA may appear successful if a patch with a valve are applied. PMID- 26817084 TI - [OPTIMIZATION OF THE SURGICAL TREATMENT RESULTS IN CONOTRUNCAL CARDIAC FAILURES IN LARGE AORTO-PULMONARY COLLATERAL ARTERIES]. AB - The results of surgical treatment of 83 patients, suffering conotruncal cardiac failures and large aorto-pulmonary collateral arteries, were analyzed. In 2007 - 2014 yrs a radical correction of the failure (RCF) was performed in 53 (64%) of them. RCF was achieved, using three surgical approaches. The algorithm of a surgical approach choice was introduced, guaranteeing the operation time shortening and artificial blood circulation application, have improved the course of early postoperative period. It was proved, that improvement of surgical results is possible, if a correct surgical tactic choosed and surgical approaches rationally applied. PMID- 26817085 TI - [INTRAOPERATIVE NAVIGATION WHILE PERFORMANCE OF CATHETERIC RADIO-FREQUENCY SYMPATHETIC DENERVATION OF RENAL ARTERY IN PATIENTS WITH REFRACTORY ARTERIAL HYPERTENSION]. AB - Clinical application efficacy of a navigation systems with a three-dimension reconstruction of aorta and renal arteries, while performance of their catheteric radiofrequency sympathetic denervation, was studied. Application of intraoperative navigation in the patients, operated on for refractory arterial hypertension, improves postoperatively the arterial pressure contol significantly. Positive clinical effect secures during 18 mo as minimum. The complications absence witnesses the method safety and expediency of its wide introduction into the practice. PMID- 26817086 TI - [SURGICAL TREATMENT OF ELDERLY AND SENILE PATIENTS FOR AFFECTION OF CARDIAC VALVES]. AB - Operations on the open heart, of them in 62 (32.9%)--the valves prosthesis, were conducted on the base of Clinical Treatment-Diagnosis Centre "Simedgroup" of Ivano-Frankivskiy National Medical University in 2012 - 2015 yrs in 188 patients. Hemodynamically significant failures of a mitral valve and/or the aortal valve were considered as indications for the operative treatment conduction. Combined surgical treatment--the valve prosthesis and coronary shunting--were conducted in coincident ischemic heart disease. More durable rehabilitation is needed for elderly and senile patients. PMID- 26817088 TI - [RESULTS OF AN ACUTE THROMBOSIS OF HEMORRHOIDAL NODES TREATMENT]. AB - The results of treatment of 182 patients, suffering an acute thrombosis of hemorrhoidal nodes of various severity, were studied. In 93 (51.1%) patients (main group) an active surgical tactics was applied. There were conducted urgent, early and postponed operations. In 89 (48.9%) patients (control group) a conservative-expectant tactic was applied. The patients were operated on in terms of 9 - 10 days after admission to hospital. The terms of operation and the method of hemorrhoidectomy were choosed without taking into account the disease severity. Complications in the main group have occurred in 27 (29%) patients, their stationary treatment have lasted 7 - 11 days. In a control group complications were revealed in 27 (30.3%) patients, their stationary stay have lasted from 9 to 28 days. PMID- 26817087 TI - [THE TREATMENT OF PATIENTS FOR ULCERATIVE-NECROTIC DEFECTS IN CHRONIC ISCHEMIA OF THE LOWER EXTREMITY TISSUES, USING BIOTECHNOLOGICAL METHODS]. AB - The results of treatment of 53 patients, suffering "unreconstructable" affection of the lower extremities (LE) arteries and ulcerative-necrotic defects in their distal parts tissues, were analyzed. In 33 patients (the main group) the allotted mononuclear cells fraction, the bone marrow and the plasm, enhanced by thrombocytes, were applied, using multiple injections along a perimeter and into the bottom of the ulcerative-trophic defect in combination with autotransplantation of the bone marrow aspirate into the ischemized tissues--the shin muscles; in 20 patients (the comparison group)--the autotransplantation of the bone marrow aspirate was accomplished into the ischemized tissues--the shin and the foot muscles. In terms up to 3 mo postoperatively a clinical improvement in the main group was noted in 25 (75.7%) patients, the bearing function of the LE was preserved in 90.9%; and in the comparison group--accordingly, in 8 (40%) and 70%. In 36 mo in the main group the bearing function of the LE was preserved in 75.7% patients, and in the comparison group--in 50%. Application of the biotechnological methods proposed in patients, suffering ulcerative-necrotic defects in chronic ischemia of the LE tissues, have promoted the angiogenesis processes activation, the tissues reparation and regeneration, the wounds healing, and the disease clinical course optimization. PMID- 26817089 TI - [APPLICATION OF LINEAR WELDING SUTURE WHILE PERFORMANCE OF A VIDEO-ASSISTED SEGMENTECTOMY FOR MULTIRESISTANT PULMONARY TUBERCULOSIS]. AB - The results of treatment of 40 patients, suffering multiresistant pulmonary tuberculosis (MRPT), were analyzed. There was proved the efficacy of the tissues biological welding while performing video-assisted segmentectomy. The duration of postoperative treatment for the patients have reduced down to (15.7 +/- 3.8) days. Clinical aprobation was conducted, concerning application of a welding complex EK300 M1 in automatic regimen while pulmonary surgery performance. Application of the algorithm elaborated, concerning providing of surgical aid for patients, suffering MRPT, guarantees a curative outcome in 97.6% of them. PMID- 26817090 TI - [DYSPLASTIC GONARTHROSIS, NEW IN DIAGNOSIS]. AB - A new diagnostic criterion, the index pathology of a knee joint, application of which permits to optimize diagnostic process and gives possibility to escape mistakes while planning of surgical treatment, was elaborated. Prognostication of a gonarthrosis formation, basing on discriminant analysis, permits to achieve a maximal accuracy in the arthrosis stage diagnosis or possibility of its occurrence in immediate time. PMID- 26817091 TI - [MINIINVASIVE OSTEOSYNTHESIS IN THE TREATMENT OF THE LONG BONES FRACTURES IN THE INJURED PERSONS WITH COMBINED TRAUMA]. AB - The apparatus for external fixation of the long bones fractures of various localization, applied in 118 injured persons, was proposed. In 86.8% patients a good results of treatment were achieved. PMID- 26817092 TI - [THE METHOD OF TREATMENT OF LYMPHORRHEA AFTER RECONSTRUCTION OF THE LOWER EXTREMITIES ARTERIES]. AB - Lymphorrhea have had occur after performance of 1381 reconstructive operative interventions on arteries of the lower extremities in 42 (3.04%) of patients. While application of 76% solution of triombrast and further elastic compression in 83.3% observations a good result was achieved, in 16.7%--satisfactory. PMID- 26817093 TI - [CHANGES OF THE HEMOSTASIS SYSTEM IN THE INJURED PERSONS IN FRACTURES OF LONG BONES OF THE LOWER EXTREMITIES]. AB - The changes of hemostasis in the injured persons, in the lower extremities long bones fracture were analyzed. Complex dynamic investigation of the hemostasis system was conducted preoperatively in 76 injured persons, in whom long bones of the lower extremities fracture have occurred, and in 31--with injury of meniscus. Instrumental diagnostic method--a low-frequency piezoelectric thromboelastography -was applied for investigation of the blood coagulation system. The shift in a system of hemostasis towards hypercoagulation, fibrinolytic and the thrombine activity inhibition, the thrombocytes spontaneous aggregation intensity, duration of formation of a clot fibrinthrombocytic structure; the blood fibrinthrombocytic constanta enhancement, a summary index of the clot retraction and spontaneous lysis reduction were revealed in a hemostasis system before start of the treatment. The hemostasis system disorders in the injured persons may cause thrombohemorrhagic complications, what trusts a necessity for rational choice of preoperative methods of prophylaxis and intensive therapy in a system of hemostasis. PMID- 26817094 TI - [OPINION OF ANESTHESIOLOGIST ON PATHOGENESIS OF SHOCK, TAKING INTO ACCOUNT THE INFUSION THERAPY POINT OF VIEW]. PMID- 26817095 TI - [POSSIBILITIES OF VIDEOESOPHAGOGASTRODUODENOSCOPY WITH HIGH RELEASING CAPACITY IN REGIMES OF HIGH ENHANCEMENT AND A NARROW-STRIP VISUALIZATION IN PREHISTOLOGICAL DIAGNOSIS OF GASTRIC CANCER]. PMID- 26817096 TI - [OBSERVATION OF ENTEROGENIC MEDIASTINAL CYST]. PMID- 26817097 TI - [PRIMARY MALT-LYMPHOMA OF THE LEFT PULMONUM, COMBINED WITH PULMONARY TUBERCULOSIS]. PMID- 26817098 TI - [THE MODERN PATIENT WITH A GASTROENTEROLOGICAL DISEASE: ADDITION TO A CLINICAL PORTRAIT]. AB - The typical features of patients with gastroenterology pathology, which have no nosological specificity were analysed: initially chronic course of diseases, combination of diseases, personal features with prevalence of depressions and frustration, an allergization, increase in frequency of a metabolic syndrome and a chronic focal infection. PMID- 26817099 TI - [HIGH FREQUENCY OF CYP2C19 ULTRARAPID METABOLIZERS IN RUSSIAN PATIENTS WITH PEPTIC ULCER]. AB - INTRODUCTION: The main enzyme responsible for metabolism of proton pump inhibitors (PPI) is cytochrome P-4502C19 (CYP2C19). Among all CYP2C19 polymorphisms ulrarapid CYP2C19*17 allele plays an important role in clinical practice as in CYP2C19*17 allele carriers acid suppression achieved with PPI including eradication regimens may be insufficient. THE AIM OF THE STUDY: To find the frequency of CYP2C19 ultrarapid metabolizers in Russian patients with peptic ulcer METHODS: We retrospectively reviewed the results of pharmacogenetic tests of 971 Russian patients with endoscopically and histologically proven ulcers, 428 male (44%) and 543 female (56%). The mean age was 44.6 +/- 11.9 years (range 15 88 years). DNA was extracted from EDTA whole blood samples (10 mL). The polymorphisms CYP2C19 *2, *3 *17 were evaluated using real-time polymerase chain reaction (RT-PCR). RESULTS: We found that among 971 peptic ulcer patients ultrarapid metabolizers (CYP2C19*1/*17, CYP2C19*17/*17) were the most frequent genotype--39.75%. Extensive metabolizers with CYP2C19*1/*1 genotype were less frequent--32.65%. Frequency of poor and intermediate metabolizers was found to be 1.5% and 25.85% respectively. We were the first to investigate CYP2C19*17 allele frequency in Russian patients with peptic ulcer which was found to be 27.4%. CONCLUSION: High frequency of CYP2C19 ultrarapid metabolizers in Russian patients with peptic ulcer may be associated with insufficient response to proton pump inhibitors. PMID- 26817100 TI - [THE INTERDEPENDENCE BETWEEN SMOKING, ALCOHOL, TOOTH PATHOLOGY AND PREVALENCE OF HELICOBACTER PYLORI AMONG ETHNIC GROUPS IN KYRGYZSTAN]. AB - The main aim was to study the ethnic and social characteristics of the prevalence of certain risk factors among Kyrgyz ethnic population infected with Helicobacter pylori without clinical signs of the disease of upper gastrointestinal tract. The study involved 116 healthy individuals (57 and 49 Kyrgyz, Russian) who were tested on H. pylori infection, taking into account risk factors such as smoking, alcohol consumption, low or serious teeth damage. The identified H.pylori infection was independent from ethnic affiliation. Significant relation between absence or high damage of the teeth and H. pylori contamination was revealed in surveyed Kyrgyz group. PMID- 26817101 TI - PECULIARITIES OF THE COURSE OF THE UPPER ALIMENTARY TRACT DISEASES IN CHILDREN WITH BRONCHOOBSTRUCTIVE SYNDROME. AB - The aim of the study was to improve the tactics of treatment of bronchoobstructive syndrome (BOS) in associative course with gastroesophageal reflux disease (GERD) in children. MATERIALS AND METHODS: 180 children aged 6-16 with diseases of the respiratory organs with BOS and GERD symptoms were examined: 85 of them--with bronchial asthma (BA), 34--with an acute course of pneumonia, 29 -with recurrent obstructive bronchitis. Comparison groups were composed of 93 children, the number of practically healthy children (the control group) was 28 persons. The analysis of risk factors of associative pathology development, roentgenographic study, investigation of the function of external respiration (FER) (peak flowmetry, spirometry), intracavitary pH-metry, esophagofibrogastroduodenoscopy (EFGDS) and ultrasonic investigation (USI) of the organs of the gastro-intestinal tract (GIT) were carried out. RESULTS: Diseases of the respiratory organs with BOS in the groups of the patients under investigation in 43.9% of cases on an average associated with GERD. In a severe course of bronchial asthma GERD was detected 3,4 times more frequently in the boys, while in a lengthy course of pneumonia with BOS--1,9 times more frequently in the girls. Chronic gastritis (ChG) and chronic gastroduodenitis (ChGD) in BA were revealed in 40.6% of the patients, in pneumonia--in 45.7%, in recurrent bronchitis--in 33.3% of the patients. Peculiarities of pre-morbid background of BA and GERD associative course were exhibited by gestosis, threat of abortion, intrauterine hypoxia of the fetus, social troubles of the family. Manifestations of BA in children in 36% of cases were observed 6-12 months after the onset of GERD. The designed individual anti-reflux programs in complex therapy of respiratory organs' diseases with BOS associated with GERD reduce the frequency of exacerbations and hospitalizations of patients with BA, improve their life quality. PMID- 26817102 TI - [STUDY OF THE VARIABILITY OF THE CARDIAC RHYTHM IN RAILROAD EMPLOYEES, WHO SUFFER BY STOMACH ULCER AND DUODENUM, ASSOCIATED AND NONASSOCIATED WITH THE INFECTION HELICOBACTER PYLORI]. AB - AIM OF INVESTIGATION: To estimate the Heart rate variability (HRV), by the method of daily kholterovskogo monitoring in the workers of rail transport (RT). MATERIALS AND METHODS: A total of 93 persons working in the East Siberian Railway. The main group (CG) consisted of 27 patients with gastric ulcer (GU) and duodenal ulcer (DU) contamination without Helicobacter infection. The first group of clinical comparison (GCS 1) included 36 patients with gastric ulcer and duodenal with contamination of infection H. pylori. The second group of clinical comparison (GCS 2) consisted of 30 employees VT held preventive medical examination, without contamination of Helicobacter infection is not suffering from gastric ulcer and duodenum. RESULTS: With the analysis of spectral and time characteristics HRV in Haug is revealed the explicit displacement of vegetative homeostasis with the prevalence of the sympathetic component of regulation, which is restored against the background of treatment. Meanwhile in GKS1 the indices of vegetative regulation had parasympathetic directivity, they were more close to the standard and did not change after conducting of the eradikatsionnoy therapy. CONCLUSION: The greatest unbalance of sympathetic and parasympathetic nervous system is observed in patients, workers (RT), who suffer SU and UD in the absence of the contamination of H. pylori. The use of a method of study VCR in the conditions of the absence of H. pylori infection can make it possible to form the group of risk of development SU and UD in workers RT. PMID- 26817103 TI - [DAILY INTRAESOPHAGEAL pH-MONITORING IN THE DIAGNOSIS OF THE SEVERITY OF ESOPHAGITIS WITH GASTROESOPHAGEAL REFLUX DISEASE]. AB - OBJECTIVE: To identify criteria of pH-grams to diagnose the severity of esophagitis and preneoplastic complications of GERD. MATERIALS AND METHODS: 63 patients aged from 18 to 70 with A, B, C degree of GERD, according to the Los Angeles classification and 15 patients with intestinal metaplasia of columnar epithelium and leukoplakia of the stratified squamous epithelium of the esophagogastric transition were examined. For daily intraesophageal pH-monitoring "Gastroscan-24", pH probes manufactured by ZAO NPP "Istok- system", Fryazino (Russia) were used. pH-grams were estimated according for indicators DeMeester. Endoscopy was performed by videoesofagogastroscopes of Evis Exera- system--160 and by the tools company "Olympus" (Japan). RESULTS: 5 options of pH-grams were selected, each of them may correspond to some degree of esophagitis, preneoplastic changes of the esophageal mucosa, esophageal and extraesophageal manifestations of GERD. CONCLUSION: Daily pH-monitoring of the esophagus can serve as a screening for the severity of esophagitis, preneoplastic changes of esophagogastric transition, for addressing the need of morphological studies and differential diagnosis of extraesophageal manifestations of GERD. PMID- 26817104 TI - [DIAGNOSTIC MARKERS FOR CHRONIC PANCREATITIS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS WITH DIFFERENT PHENOTYPE]. AB - The purpose--to study the relationships between levels of apelin, elastase-1 and tumor necrosis factor-alpha (TNF-alpha) in patients with chronic pancreatitis (CP), type 2 diabetes mellitus (T2DM) and with combined course of its with a different phenotype. MATERIALS AND METHODS: The investigation involved of 114 patients with CP, type 2 diabetes mellitus and with combined course of its with a different phenotype. The control group consisted of 20 healthy individuals. RESULTS: It was found that patients with combined course of CP and type 2 diabetes with overweight had significantly higher hyperapelinemia and hyper-TNF alpha-emia (p < 0.05). Patients of all study groups revealed a close correlation between apelin and TNF-alpha (p < 0.05), a significant correlation between apelin and elastase-1 (p < 0.05). As a result of analysis of variance identified significant contribution of study diseases and different phenotypes in levels of apelin, TNF-alpha and elastase-1. CONCLUSIONS: The results of the study suggest that the levels of apelin, TNF-alpha and elastase-1 are important diagnostic markers of CP in patients with type 2 diabetes mellitus. PMID- 26817105 TI - [EXPERIMENTAL FOUNDATION FOR LINSEED AND WALNUT OILS APPLICATION IN GASTROENTEROLOGY]. AB - In the article the influence of the hepatotropic effect of linseed and walnut oils on the lipid composition of the rats' blood serum under CCl4 intoxication has been presented. Lipid metabolism was characterised by the assessment of total cholesterol content in the blood serum, non-etherified cholesterol, cholesterol ethers, cholesterol lipoproteids of high-, low- and very low- density as well as triaclglycerins. In rats with experimental severe liver insufficiency associated with cholesterol increase in low-density lipoproteid fraction alongside its decrease in high-density lipoproteid fraction hypercholesterolemia was progressing. Cholesterol etherification inhibition (by 31.1%) was also observed. The tendency to less intensive disorders (by 1.7-2.0) as well as the tendency to lipid metabolism normalisation in animals have been revealed under the influence of lipophilic substances studied. PMID- 26817106 TI - [GASTROINTESTINAL COMPLICATIONS OF ANTICOAGULANT THERAPY IN PATIENTS WITH NON VALVULAR ATRIAL FIBRILLATION]. AB - Non-valvular atrial fibrillation is the most common cardiac source of emboli and cardioembolic stroke. Anticoagulants are recommended for preventing stroke in patients with non-valvular atrial fibrillation. Warfarin reduces the risk of stroke in patients with AF by approximately two-thirds. Several novel anticoagulants that can overcome the limitations of warfarin have been introduced in the market or are under development. The NOACs are at least as effective as warfarin for stroke prevention in AF. Bleeding complications, including gastrointestinal bleeding, are common complication of anticoagulant treatment. The NOACs therapy are associated with an increased risk of major gastrointestinal bleeding compared with warfarin, and dabigatran is associated with an increased risk of non-bleeding upper GI symptoms such as dyspepsia and heartburn. This review provides information on the safety and risks of using NOACs, methods of treatment of gastrointestinal complications events in patients with non-valvular atrial fibrillation. PMID- 26817107 TI - [NSAID GASTROPATHY IN PATIENTS WITH COMORBID DISEASES]. AB - The widespread use in clinical practice of non-steroidal anti-inflammatory drugs (NSAIDs), largely due to the general trend towards an aging population and, as a consequence, increase the number of individuals with comorbid conditions and diseases, including the most common are diseases of the cardiovascular system, diseases of the joints and spine, requiring of therapy with, combining the anti inflammatory and analgesic properties. However, NSAIDs not only have favorable effects, but have quite a wide range of adverse effects, an important place among which is NSAID-induced gastropathy. The article deals with the rational choice of NSAIDs in patients depending on the degree of cardiovascular risk and gastrointenstinalnogo, as well as the possibility of preventing NSAID-associated gastropathy. Particular attention is paid to the choice of individual NSAIDs with regard to their pharmacological properties. PMID- 26817108 TI - [DRUG-INDUCED LIVER DISEASE IN MULTICOMPONENT THERAPY OF COMORBID CONDITIONS]. AB - The problem of drug liver lesions is of particular relevance in our time, when the application of medical standards in different disease groups includes 8-12 medicines in case of simultaneous reception (polypharmacy), which may cause the development of different forms drug-induced hepatotoxic reactions in 28% of cases. For diagnosis it is necessary to consider the baseline characteristics of the patient, the properties of drugs, duration and dose of administration. There are international criteria for the evaluation of medicinal liver lesions, including the time interval for the reaction after drug withdrawal, exclusion of alternative causes of liver damage and a positive response to repeated administration of the drug. It is mandatory for differential diagnosis to exclude other forms of liver damage viral and non-viral etiology. Thought the purpose of each drug, and in the case of drug liver damage--adequate and timely recruitment hepatoprotective therapy based on the molecular mechanisms of pathogenesis will not only contribute to the reduction of risk factors hepatotoxic manifestations, but also the possibility to conduct a complete comprehensive treatment of the underlying pathological process. PMID- 26817109 TI - [MICROFLORA AND ORAL DISEASE]. AB - Acid-producing microorganisms are base etiological agents of lesions of tooth enamel and destruction of dentin. The process start by specific microflora of tooth deposit--Streptococcus mutans, Lactobacteria and Actinomycetis viscosus which ferment food carbogydrate to form acids. High titre of them in oral cavity may be considered like a marker of carbohydrate food. But the pathogenic bacteria don't have aggression to host organism until they will have virulent factors which help to get over protection of host organism. At the same time, microflora of oral cavity is involved to form pellicula. Pellicula is a biofilm which to protect tooth enamel and dentin. Understanding relationships between safety factors of host and pathogenic microflora of oral cavity will give to create effective methods of prevention and treatment. PMID- 26817110 TI - [VITAMIN D DEFICIENCY AS A FACTOR POLYMORBIDITY]. AB - One of the factors in the polymorbidity development are systemic metabolic changes such as lipid disorders, mineral metabolism, glucose metabolism, hormonal status. The article highlights the current knowledge about the metabolic role of vitamin D, it is concluded that the vitamin D deficiency is a factor of polymorbidity. PMID- 26817111 TI - [SIGNIFICANCE OF MAGNESIUM IN PHISIOLOGY AND PATHOLOGY OF THE DIGESTIVE SYSTEM]. AB - The article describes the physiological role of magnesium in the human body and its importance for metabolic processes. The reasons for the development of magnesium deficiency and hypermagnesaemia and its clinical symptoms are shown. The specialties of magnesium metabolism disturbances in gastroenterological pathology are described. Particular attention paid to the correction of magnesium levels with deviations of its content in the organism. PMID- 26817112 TI - [GLOSSALGIA SYNDROME AS SUPRAESOPHAGEAL MANIFESTATION OF GASTROESOPHAGEAL REFLUX DISEASE]. AB - The case of clinical supervision of the patient having polimorbid pathology is presented. One of extraesophageal manifestations of a gastroesophageal reflux disease is the glossalgia. Glossalgia is the polyetiological disease. Treatment needs to be carried out taking into account the factors causing emergence of a glossalgia. In this regard normalization of functions of organs and systems of an organism is provided. PMID- 26817113 TI - [UNMODIFIED DIAMETER V. PORTA. IN 79-YEAR-OLD PATIENT WITH CONGESTIVE HEART FAILURE AND SEVERE PULMONARY HYPERTENSION IN THE SETTING OF COMPLEX CONGENITAL HEART DISEASE--PATENT FORAMEN OVALE AT THE CONFLUENCE OF THE LEFT PULMONARY VEINS INTO THE V. CAVA SUPERIOR AND MIXED (HCV) LIVER CIRRHOSIS]. AB - The clinical observation and analysis of the reasons for late diagnosis of congenital heart disease is presented. A feature of this observation is diagnosed complex congenital heart defect with shunting of blood in elderly woman with the second disease--chronic viral hepatitis C and cirrhosis of the liver. Long-term compensation circulation and lack of pulmonary fibrosis in our patient with patent foramen ovale was due to the presence of a second malformation--confluence of the left pulmonary veins in vena cava superior that apparently contributed to the constant lung tissue haemooxygenation. PMID- 26817114 TI - ARTERIAL EPONYMS IN GASTROINTESTINAL TRACT. AB - Eponym--name of the disease, certain structure or method after the person who usually first discovered and described them. Eponyms are widely spread in medicine which appeared to be in the area of a great interest for a lot of scientists. They can serve as a reflection of the evolution of the medical knowledge and making up the majority of anatomical terms. The article describes 12 arterial eponyms of the gastrointestinal tract giving a full anatomical description. It also gives an explanation of why and how those structures were named after certain scientists and what contribution they've made into the development of medicine. PMID- 26817115 TI - [THE REPORT ABOUT THE XVTH JUBILEE CONGRESS OF GASTROENTEROLOGICAL SCIENTIFIC SOCIETY OF RUSSIA, THE 17TH INTERNATIONAL SLAVIC-BALTIC SCIENTIFIC FORUM "ST. PETERSBURG--GASTRO 2015" AND EUROPEAN ASSOCIATION FOR GASTROENTEROLOGY, ENDOSCOPY AND NUTRITION (EAGEN) POSTGRADUATE COURSE "MODERN SOCIETY LIFESTYLE, NUTRITION AND GI DISORDERS"]. PMID- 26817116 TI - [GENUS ANELLOVIRIDAE VIRUSES IN CHRONIC LIVER DISEASE]. AB - AIM: Viruses from genus Anelloviridae (TTV, TTMDV and TTMV) are small DNA viruses that are widespread in human popu- lation. Data on tissue tropism, cell localization and morphometry of anelloviruses are scarce. The purpose of this study was to determine the prevalence of TTV, TTMDV and TTMV in persons with liver disease and in healthy individuals, as well as electron-microscopic verification of Anelloviridae species. METHODS: Detection of anelloviral DNA was performed in serum samples from 203 patients with liver diseases of various etiology and 115 voluntary blood donors using PCR with primers allowing to differentiate TTV, TTMDV TTMV based on the length of amplified fragment. Histopathological and electron microscopic studies were performed for liver biopsy specimens from 203 patients with liver disease. RESULTS: High prevalence (70-90%) of all three anelloviruses in healthy individuals and patients with liver disease was demonstrated, with high frequency of triple TTV, TTMDV and TTMV infection (52.2-55.7%). Electron-microscopic study of liver biopsy specimens from TTMDV monoinfected patients gave a submicroscopic image of TTMDV virions with diameter 35.86 +/- 2.04 nm. Electron microscopic studies confirmed the nature of liver damage in TTMDV monoinfection: accumulation of virus in the hepatocytes, significant cyropathy with enlightenment matrix of the cytoplasm and reduction of intracellula organelles involved in protein synthesis, portal and perivascular perisinusoidal fibrosis. TTV, TTMDV and TTMV virions were dentified in hepatocytes, confirming these viruses to be hepatotropic. CONCLUSION: Our results demonstrate that anelloviruses are lymphotropic viruses, individual genotypes of those might be hepatotropic and pathogenic to liver. PMID- 26817117 TI - [COMPARISON OF DIFFERENT TREATMENT REGIMENS IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE]. AB - AIM OF INVESTIGATION: To compare the effectiveness of different treatment strategies of nonalcoholic fatty liver disease. METHODS: 51 patients with nonalcoholic steatohepatitis (NASH) were included in an open randomized prospective comparative study with no control. Patients were divided into 2 groups depending on the chosen treatment strategy. Group 1 (n = 25) had been receiving standard treatment of NASH (Ursodeoxycholic acid 15 mg/kg once a day, per os divided into 3 doses, Atorvastatin 20 mg per os at night, Vitamin E 800 IU/day per os for 12 months); Group 2 (n = 26) had been receiving losartan 50 mg/day per os for 12 months in addition to the above mentioned standard treatment of NASH. STUDY RESULTS: In overall, the results of this work suggest that long term, for 12 months, losartan usage in a daily dose of 50 mg in the complex therapy of patients with NASH is followed by a significant decrease in the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in serum and improvement in 13C-metathetin breath test results. These results indicate a decrease in inflammation and slowing of formation and regression of liver fibrosis. Absence of progress in liver fibrosis in patients on losartan treatment was revealed. CONCLUSIONS: Additional inclusion of losartan in the standard therapy of NASH has a positive therapeutic effect on the process of fibrogenesis in the liver, so it is advisable to appoint losartan in a daily dose of 50 mg for 1 year to these patients. PMID- 26817118 TI - [DYNAMIC OF CLINICAL, LABORATORY AND SONOGRAPHIC PARAMETERS AFTER SUCCESSFUL LITHOLITIC THERAPY AT PATIENTS WITH GALLSTONE DISEASE IN ASSOCIATION WITH METABOLIC SYNDROME]. AB - The aim of study was to determine the leading clinical, immunological and sonographic pararneters, reflecting the efficiency of Ursodeoxycholic acid (UDCA) at the rate of 10 mg per 1 kg of body weight in the treatment of gallstone disease in patients with metabolic syndrome (MS). MATERIALS AND METHODS: An assessment of clinical, biochemical immunological and sonographic parameters in 54 patients with gallstone disease associated with the metabolic syndrome before and after the six-month treatment UDCA were made. RESULTS: In accordance with our results the significant predictors, reflecting successful litholitic therapy at patients with gallstone disease in association with metabolic syndrome are decrease the serum concentration of gamma-glutamyltranspeptidase (P = 0.003), matrix metalloproteinase-9 (P = 0.001), increase the serum concentration of tissue inhibitor of metalloproteinases-1 (P = 0.02), decrease the left liver lobe thickness (P = 0,003) and the thickness of gallbladder wall (P = 0.0002). CONCLUSION: The results of our study have shown that the therapy with ursodesoxycholic acid of patients with metabolic syndrome leads to decrease of factors of gallstone progression (elevated levels of gamma glutamyltranspeptidase, matrix metalloproteinase-9 and increased thickness of the left lobe liver and gallbladder wall). PMID- 26817119 TI - CYSTIC ECHINOCOCCOSIS: EPIDEMILOGICAL AND CLINICAL ASPECTS OF LATVIAN POPULATION AND REVIEW OF THE LITERATURE. AB - INTRODUCTION: Cystic echinococcosis is an infection caused by the tapeworm Echinococcus granulosus, this form of echinococcosis is chronic, complicated, however, there is restricted knowledge about it. METHODS: Medical records of a total of 127 patients were used, of which 44 patients were selected for analysis. These were the patients with a fully verified diagnosis, a parasitic lesion located in the liver and a detailed documented ultrasound description of the condition of the liver at diagnosis. The following information was collected from the clinical records: demographic data (age, sex), diagnostic method (ultrasound (US) examination and parasitological serology), clinical data (symptoms), cyst details (number, localization, and size) and treatment. Parasitic cysts of the selected patients were analysed and the disease was classified according to World Health Organisation recommendations. RESULTS: Out of 44 selected patients, 32 were female and 12 were male. Patients' age varied from 27 to 83 (mean--55.34 15.33) years. Time until diagnosis ranged from the absence of complaints to a period of 180 months; the median time was 6 +/- 6 months. The most common complaints were pain or discomfort in the abdomen (n=20). The analysis of the stage of the cyst at the moment of the diagnosis showed that most often the 3rd (n = 9) and the 4th stage (n = 20) cysts were found. The parasitic lesion was localised in the right hepatic lobe (n = 29), it was solitary (n = 24) and of average size 6.49 +/- 3.73 cm. Results indicated that the cysts which were initially in the 5-10 cm size group were progressing more rapidly. Chemotherapy lasting for 3 years resulted in finding statistically important changes of the cysts in 20% of the patients--degenerative processes attesting the death of the parasite. CONCLUSIONS: It is necessary to develop a system that would allow identifying of patients at as early stages of the disease as possible, in order to ensure more efficient treatment and to avoid major impact on patients' quality of life by the disease. PMID- 26817120 TI - [DETERMINING THE DEGREE OF LIVER DYSFUNCTION IN CHILDREN WITH POSITIONS OF THE INTERNATIONAL CLASSIFICATION OF FUNCTIONING, DISABILITY AND HEALTH (ICF)]. AB - METHODS: Based on a retrospective analysis of biochemical blood parameters which characterize the role of liver function in the metabolism of proteins, fats and carbohydrates (considered indicators of ALT, AST, De Ritis coefficient, bilirubin, albumin, fibrinogen, prothrombin, transferrin, ceruloplasmin, cholesterol, urea, ammonia, glucose, lactate) in 95 children without liver pathology, 15 children who died of liver failure, 295 patients with various liver diseases who were treated in the SCCH, a scale system was developed as a support tool to assess liver dysfunction. RESULTS: Each biochemical indicator was assessed on a five-point scale. The level of a biochemical indicator, which corresponded to the absence of disorders, was estimated as 4 points, corresponding to "insignificant disorders"--as 3 points, "moderate disorders"--as 2 points, "severe disorders"--as 1 point, "absolute disorders"--as 0 points. The total score is the estimate of the degree of liver dysfunction. According to the recommendations of the International Classification of Functioning, Limitations of vital activities and Health, the decrease of the number of points on 0-4% (54 56 points) corresponds to the absence of the liver dysfunction, on 5-24% (43-53 points)--insignificant disorders of liver function, on 25-49% (29-42 points)- moderate hepatic impairment, on 50-95% (3-28 points)--severe disturbances of liver function, on 96-100% (0-2 points)--absolute dysfunction of the liver. CONCLUSIONS: A scoring system of assessing liver dysfunction can be applied at any stage of the examination and treatment of children of any age, as used in biochemical parameters do not depend on the age of the patient. It is an objective criterion for assessing the degree of liver dysfunction and can be used to assess the severity of the pathological process in the dynamics determining the prognosis of the disease and can be the criterion of the indications for liver transplantation, and also used during the of medico-social expert examination. PMID- 26817121 TI - [THE DIAGNOSTIC AND TREATMENT ALGORITHM FOR PATIENTS WITH OBSTRUCTIVE JAUNDICE SYNDROME]. AB - The article presents a comparative analysis of therapeutic and diagnostic measures aimed at eliminating jaundice complicating diseases hepatopancreatoduodenal zone as tumor and benign etiology. Patients with obstructive cholestasis were represented by two groups: the main and control, including 858 and 869 patients, respectively. Therapeutic and diagnoctic tactics in the study group was based on the principles of the proposed algorithm. Using the proposed diagnostic and treatment algorithm led to better outcomes: significantly lower mortality and the incidence of postoperative complications PMID- 26817122 TI - [HEPATIC ENCEPHALOPATHY AND TISSUE ZINC LEVELS IN LIVER DISEASE, DIAGNOSIS AND TREATMENT]. AB - THE PURPOSE OF THE REVIEW: Description One of the complications of liver disease- hepatic encephalopathy as well as its relationship with the content of zinc in the body. THE MAIN PROVISIONS: The review provides the key moments of the pathophysiology and clinical hepatic encephalopathy. The basic drugs and treatment regimens of hepatic encephalopathy. Data are considered the original author's research on the relationship of gravity of hepatic encephalopathy and tissue zinc levels in patients with hepatitis and cirrhosis of viral etiology. The data of modern meta-analyzes of complex treatment of hepatic encephalopathy and the role of L-ornithine-L-aspartate. CONCLUSION: Understanding the pharmacological mechanisms of action of L-ornithine-L-aspartate allow gastroenterologist physicians and general practitioners to adequately apply the drug, select the required readings and prioritize the treatment of patients with liver diseases at different stages of the disease. Should be included in the treatment regimen of hepatic encephalopathy zinc supplements. PMID- 26817123 TI - [HEMOCHROMATOSIS IN CLINICIAN PRACTICE]. AB - The paper presents the current data on the etiology, pathogenesis, clinical features, diagnosis and treatment of patients with hemochromatosis. Particular attention is given to hereditary hemochromatosis and its genetic diversity. The clinical example demonstrates the difficulty of a disease diagnostics caused by genetic polymorphism. PMID- 26817124 TI - [SUCCESSFUL ORTHOTOPIC LIVER TRANSPLANTATION IN A PATIENT WITH HEPATOLENTICULAR DISEASE AND FULMINANT HEPATIC FAILURE]. AB - The article presents a clinical case of hepatolenticular disease in young man with rapidly progressive liver disease fulminant hepatic failure and successful emergency orthotopic liver transplantation. PMID- 26817125 TI - THINK PORPHYRIA: CASE REPORT AND REVIEW OF LITERATURE. AB - Porphyrias are a group of rare disorders caused by enzyme defects in haem biosynthesis pathway. Acute intermittent porphyria is the most common hepatic porphyria. The disorder presents with severe neuropathic abdominal pain that can be accompanied by a wide range of gastrointestinal, psychiatric and neurological symptoms, making the diagnosis clarification very challenging. We report a case of a 27-year-old female patient who presented with acute abdominal pain, vomiting and marked hyponatremia, developed seizures and disorientation, and eventually required intensive care unit treatment to maintain breathing. Her symptoms were initially misinterpreted as a functional gastrointestinal disorder, thus delaying the needed specific treatment. She was diagnosed a week after the initial hospital admission, and her condition improved after receiving treatment with intravenous glucose and haemin. For patients with acute neurovisceral attacks, early clinical recognition is essential. Severe hyponatremia, urine that develops orange colour on exposure to light and gastrointestinal symptom combination with neurologic symptoms are three valuable clues that may lead to the right diagnosis faster. Pathophysiology of hyponatremia in case of acute intermittent porphyria in only partly understood and can be associated with syndrome of inappropriate antidiuretic hormone secretion, gastrointestinal or renal sodium loss. PMID- 26817126 TI - [SCLEROUSIS CHOLANGITIS AT THE AUTOIMMUNE PANCREATITIS PATIENT]. AB - The article contains the description of a clinical case of the patient P. of 59 years with autoimmune pancreatitis (AIP) associated with a sclerousis cholangitis (SC), and the analysis of literature on this problem. The patient was operated (cholecystenterostomy, enteroenterostomy) for pancreatic cancer. The pancreatic cancer was excluded. Overlap syndrome (primary biliary cirrhosis/autoimmune hepatitis), pseudotumorosis pancreatitis were excluded during the period of monitoring in hospitals of Moscow. In our clinic the diagnosis AIP is established on the basis of Mayo's criterion (HISORt: Histology, Imaging, Serology, Other organ involvement, Response to corticosteroid therapy). The increased level of immunoglobulin G (IgG) by 3 times (46,2 g/l, norm--6.58-18.37 g/l), IgG4 by 25 times (49.5 g/I, norm--0.33-2.01 g/l) was revealed. MRI of abdominal organs showed diffusion increase pancreas with a peripheral hypointensive rim, local stenosis of the Major pancreatic duct in the head pancreas. Immune histochemical study surgical biopsy of pancreas showed large number of IgG-positive plasma cells. Glucocorticosteroids (GCS, prednisolone 40 mg/d), ursodeoxycholic acid 1000 mg/d, creon 120000 ed/d promoted improvement of clinical picture AIP and decrease IgG4 (to 6.4 g/I). After 12 months IgG4 wasn't defined. Control MRI revealed dilatation small biliary ducts in 8, 5, 4 liver segments and thickening wall common bile duct (to 2 mm) at large distance. The peculiarity of the case- the 15-year follow-up of patients with AlP who had inappropriate surgery. Late diagnosis and delayed treatment GCS adversely affected the course of the disease, which led to the development of secondary biliary cirrhosis. PMID- 26817127 TI - [NONALCOHOLIC FATTY LIVER DISEASE: DIAGNOSTIC, SYMPTOMS, TREATMENT. GUIDELINES WERE APPROVED BY THE XV GASTROENTEROLOGICAL SCIENTIFIC SOCIETY OF RUSSIA IN 2015]. AB - According to the World Health Organization, it is recorded steady growth of the number of chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD), in recent years. As an independent nosological entity, NAFLD is one of the risk factors for cardiovascular diseases, associated with abdominal-visceral obesity, peripheral insulin resistance (IR), and is regarded as the hepatic component of Metabolic syndrome (MS). Nowadays there are no generally accepted national standards for diagnosis and treatment of NAFLD for physicians, gen- eral practitioners, gastroenterologists in Russia. This was the essential reason in their development. The main reason of The guidelines development is the absence of generally accepted national standards for diagnosis and treatment of NAFLD for physicians, general practitioners, gastroenterologists in Russia. These guidelines are based on the global and local data of treatment experience of NAFLD, recently published in reviews, analytical studies in the literature. Guidelines are intended for physicians, general practitioners, gastroenterologists and contain the description of the preferred approaches to the provision of diagnostic, curative and preventive care of patients NAFLD. The quality of recommendations was grading according to the GRADE approach. PMID- 26817128 TI - [AUTOIMMUNE LIVER DISEASES: CLINICAL FEATURES, DIAGNOSIS, TREATMENT. GUIDELINES WERE APPROVED BY THE XV GASTROENTEROLOGICAL SCIENTIFIC SOCIETY OF RUSSIA IN 2015]. AB - The group of liver autoimmune diseases (LAD) includes autoimmune hepatitis (AIH), Primary biliary cirrhosis (PBC) and Primary sclerosing cholangitis (PSC) The guidelines on clinical diagnosis and management of patients based on a review and analysis of recent publications on this topic in the global and domestic literature and on the authors'experience in treating patients with autoimmune liver disease. PMID- 26817130 TI - [Ocular Infection is the Reflection of Society]. PMID- 26817129 TI - [WILSON'S DISEASE (HEPATOLENTICULAR DEGENERATION, DYSTROPHIA HEPATOCEREBRALIS) DIAGNOSIS, TREATMENT AND DISPENSARY OBSERVATION. GUIDELINES WERE APPROVED BY THE XV GASTROENTEROLOGICAL SCIENTIFIC SOCIETY OF RUSSIA IN 2015]. AB - Wilson's disease (hepatolenticular degeneration, dystrophia hepatocerebralis)--a chronic, progressive disease with a genetically determined autosomal recessive mode of inheritance. The violence in metabolism of copper with its excessive accumulation in visceral organs and central nervous system is the basis of the disease. The guidelines on clinical diagnosis and management of patients based on a Review and analysis of recent publications on this topic in the global and Domestic literature and on the authors' experience in treating patients with Wilson's disease. PMID- 26817131 TI - [Comparison of 12 Months Outcome of As-needed Intravitreal Aflibercept or Ranibizumab for the Treatment of Naive Patients with Age-related Macular Degeneration]. AB - PURPOSE: To compare pro re nata (PRN) intravitreal injections of aflibercept (IVA) and ranibizumab (IVR) in patients with treatment naive age-related macular degeneration (AMD). MATERIAL AND METHODS: We analyzed 42 eyes that receive 3 times monthly IVA as introduction phase and subsequently received PRN retreatment at the recurrence. As the control, 56 eyes received the same IVR treatments as the IVA criteria. We statistically analyzed chronological changes of VA and the first recurrence following introduction phase by comparing the findings of the 2 groups. RESULTS: There was no difference in the IVA and the IVR in baseline visual acuity (VA) and the mean number of injections during 12 months. Compared to the IVR, the IVA showed better improved VA from baseline at each time point, especially, there was a statistically significant difference in 6 months after introduction (p = 0.041). The IVA proved to have a shorter period until the first recurrence and a lower remission maintenance rate following introduction phase than the IVR. The improvement of VA above 0.2 logMAR was significantly related to cases involving polypoidal choroidal vasculopathy, greatest linear dimension and baseline VA. CONCLUSIONS: The improvement of VA in anti-VEGF therapy for AMD was influenced by the disease type or pathology rather than the choice of therapeutic agents. PMID- 26817132 TI - [Factors Affecting Uncorrected Visual Acuity following Implantation of Apodized Diffractive Intraocular Lenses]. AB - PURPOSE: To investigate the preoperative factors affecting postoperative uncorrected visual acuity (UCVA) equal to or more than 20/20. SUBJECTS AND METHODS: One hundred sixty seven eyes receiving apodized diffractive multifocal intraocular lenses (SN6AD1) were included in this study. In the eyes with corneal astigmatism of less than 1.0 D, a 2.4 mm clear temporal corneal incision was created. In those equal to or more than 1.0 D, 4.1 mm steepest meridian clear corneal incisions and/or limbal relaxing incisions were conducted. Preoperative factors affecting postoperative UCVA equal to or more than 20/20 were assessed by univariate analysis and multiple logistic regression analysis. RESULTS: Patient's age and preoperative corneal astigmatism were significant in both univariate analysis and multiple logistic regression analysis. The ratio of postoperative UCVA equal to or more than 20/20 was significantly lower in the patients 70 years or older and in the eyes with corneal astigmatism equal to or more than 1.5 D. CONCLUSION: Multifocal toric intraocular lenses provide better surgical results in eyes with corneal astigmatism, however patient's age needs to be considered as a factor affecting UCVA. PMID- 26817133 TI - [Infection post Excimer Laser Corneal Refractive Surgery]. AB - PURPOSE: To report the cases with severe infection post excimer laser refractive surgery. METHODS: This study involved 6 eyes of 4 women (mean age 38 years, range : 27-51 years) who underwent excimer laser corneal refractive surgery. RESULTS: In all 4 cases, the respective primary causative organisms of the infection were quinolone-resistant methicillin-sensitive Staphylococcus aureus, quinolone resistant methicillin-resistant Staphylococcus aureus, yeast type fungus, and in 1 case, penicillin-resistant Streptococcus pneumoniae. We initiated topical antibiotics or intensive antifungal treatment, yet due to severe inflammation and ophthalmalgia, analgesic drugs were needed. An average hospitalization period was 38.5 days (range : 22-77 days), and the best spectacle-corrected visual acuity was 0.5 or more than 0.5 post discharge. CONCLUSIONS: In the treatment of severe corneal infection post refractive surgery, it is important to identify the primary causative organism. If the response to the initial treatment is poor, such patients should immediately be referred to a special clinic to obtain a better visual outcome. PMID- 26817134 TI - [Severe Ocular Infection in Elderly Patients with Dementia: a Case Study]. AB - Purpose : To report 3 cases of severe ocular infection in elderly patients with dementia. CASE REPORTS: Case 1 involved a 75-year-old man who presented after his wife noticed hyperemia and discharge in his right eye. Corneal infection with perforation was found. Wife-administered antibiotics healed the infection within 1 month. Case 2 involved a 97-year-old man who was referred to us after nursing home staff members noticed redness and discharge in his right eye. Severe corneal infection with hypopyon was found. Following systemic and topical and antibiotics' administration by the nursing-home staff, the infectious keratitis healed within 2 weeks. Case 3 involved an 80-year-old woman referred to us from another clinic due to persistent epithelial defect in her left eye. Since the defect was accompanied by anterior uveitis and vitreous opacity, we suspected bacterial endophthalmitis. Following systemic and topical antibiotics' administration by family members, signs of infection diminished within 3 weeks. In all 3 cases, medical examination was difficult, topical eye-drop instillation by the patients themselves was impossible. CONCLUSIONS: In elderly dementia patients, cognizance of infection, medical examination, and treatment are difficult. Support by family members or nursing-home staff is necessary to obtain improved outcomes. PMID- 26817135 TI - Hypersensitivity Reactions to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Selective Reactions. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are used throughout the world to treat pain and inflammation; however, they can trigger several types of drug hypersensitivity reactions (DHRs) in all age groups. Although most such reactions occur through activation of the leukotriene pathway without specific immunological recognition (cross-intolerance), a significant number of DHRs to NSAIDs are due to immunological mechanisms (selective reactions [SRs]). SRs are thought to be induced by specific IgE antibodies or by T cells. In this manuscript, we focus on SRs, which are of great concern in children and adolescents and comprise a heterogeneous set of clinical pictures ranging from mild entities such as urticaria/angioedema to potentially life-threatening conditions such as Stevens-Johnson syndrome/toxic epidermal necrolysis. Paracetamol and ibuprofen are the most frequent elicitors of IgE-mediated SRs, although pyrazolones have also been implicated. T cell-mediated reactions are infrequent in children but have been associated with ibuprofen, naproxen, and dipyrone. In this review, we analyze the available literature on SRs in children and adolescents, with emphasis on epidemiological data, mechanisms, and drugs involved, as well as on diagnostic procedures. PMID- 26817136 TI - Nasal Hyperreactivity: Nonspecific Nasal Provocation Tests. Review by the Rhinoconjunctivitis Committee of the Spanish Society of Allergy and Clinical Immunology. AB - Nasal hyperreactivity is the abnormal reaction of nasal tissue to a stimulus that is innocuous to most people. This response is caused by dysregulation of the autonomic nervous system at various levels of the nasal autonomic reflex arc. Various stimuli (methacholine, histamine, adenosine 5'-monophosphate, cold air, mannitol, rapsaicin, phentolamine, and distilled water) have been used in an attempt to find the test that most reliably differentiates between healthy individuals and patients and also between different types of rhinitis. Despite the small number of publications available, in the present review, we provide an update on current nonspecific nasal provocation techniques. The studies published to date are not comparable: the stimuli applied act through different mechanisms and are used to assess different pathways, and the methodologies differ in terms of selection of participants, concentrations used, and assessment of response (criteria for positivity). Given the limited use of nonspecific nasal provocation tests in routine clinical practice, we believe that more studies are warranted to address the research issues we present at the end of the present review, for example, the need to standardize the methodology for each test or even the clinical benefits of knowing whether or not a patient has nasal hyperreactivity. PMID- 26817137 TI - Self-Management of Anaphylaxis Is Not Optimal. AB - BACKGROUND: Our objective was to ascertain the degree of adherence to recommendations made to patients with anaphylaxis, most of whom were attended in our allergy outpatient clinic. METHODS: A questionnaire was sent to 1512 patients who had experienced anaphylaxis and completed by 887. The chosen definition of anaphylaxis was that of the National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network Symposium. We evaluated the prescription, purchase, and use of epinephrine auto-injectors and oral drugs, as well as the avoidance of allergens involved in previous anaphylaxis episodes. RESULTS: Most patients (94.53%) reported that they had received advice on avoidance of responsible allergens after their allergy workup. Epinephrine auto injectors and oral drugs were prescribed according to the subtype of anaphylaxis. Only 30.74% of patients used the epinephrine auto-injector; 54.26% took oral medication. Most patients (88.3%) avoided the allergen. CONCLUSIONS: Despite general agreement that anaphylaxis occurring in the community should be treated with epinephrine auto-injectors, use of these devices to treat recurrences was low in our patients. Oral medication intake was more common than the epinephrine auto-injector in all subtypes. In order to increase adherence to epinephrine auto injectors, it is necessary to think beyond the measures recommended during regular visits to allergy outpatient clinics. PMID- 26817138 TI - Primary Antibody Deficiency in a Tertiary Referral Hospital: A 30-Year Experiment. AB - BACKGROUND: Primary antibody deficiency (PAD) is the most common group of primary immunodeficiency disorders (PID), with a broad spectrum of clinical features ranging from severe and recurrent infections to asymptomatic disease. OBJECTIVES: The current study was performed to evaluate and compare demographic and clinical data in the most common types of PAD. MATERIALS AND METHODS: We performed a retrospective review of the medical records of all PAD patients with a confirmed diagnosis of common variable immunodeficiency (CVID), hyper IgM syndrome (HIgM), selective IgA deficiency (SIgAD), and X-linked agammaglobulinemia (XLA) who were diagnosed during the last 30 years at the Children's Medical Center, Tehran, Iran. RESULTS: A total number of 280 cases of PAD (125 CVID, 32 HIgM, 63 SIgAD, and 60 XLA) were enrolled in the study. The median (range) age at the onset of disease in CVID, HIgM, SIgAD, and XLA was 2 (0-46), 0.91 (0-9), 1 (0-26), and 1 (0-10) years, respectively. Gastrointestinal infections were more prevalent in CVID patients, as were central nervous system infections in XLA patients. Autoimmune complications were more prevalent in HIgM patients, malignancies in CVID patients, and allergies in SIgAD patients. The mortality rate for CVID, HIgM, and XLA was 27.2%, 28.1%, and 25%, respectively. No deaths were reported in SIgAD patients. CONCLUSIONS: SIgAD patients had the best prognosis. While all PAD patients should be monitored for infectious complications, special attention should be paid to the finding of malignancy and autoimmune disorders in CVID and HIgM patients, respectively. PMID- 26817140 TI - Inflammatory Asthma Phenotype Discrimination Using an Electronic Nose Breath Analyzer. AB - BACKGROUND AND OBJECTIVE: Patients with persistent asthma have different inflammatory phenotypes. The electronic nose is a new technology capable of distinguishing volatile organic compound (VOC) breath-prints in exhaled breath. The aim of the study was to investigate the capacity of electronic nose breath print analysis to discriminate between different inflammatory asthma phenotypes (eosinophilic, neutrophilic, paucigranulocytic) determined by induced sputum in patients with persistent asthma. METHODS: Fifty-two patients with persistent asthma were consecutively included in a cross-sectional proof-of-concept study. Inflammatory asthma phenotypes (eosinophilic, neutrophilic and paucigranulocytic) were recognized by inflammatory cell counts in induced sputum. VOC breath-prints were analyzed using the electronic nose Cyranose 320 and assessed by discriminant analysis on principal component reduction, resulting in cross-validated accuracy values. Receiver operating characteristic (ROC) curves were calculated. RESULTS: VOC breath-prints were different in eosinophilic asthmatics compared with both neutrophilic asthmatics (accuracy 73%; P=.008; area under ROC, 0.92) and paucigranulocytic asthmatics (accuracy 74%; P=.004; area under ROC, 0.79). Likewise, neutrophilic and paucigranulocytic breath-prints were also different (accuracy 89%; P=.001; area under ROC, 0.88). CONCLUSION: An electronic nose can discriminate inflammatory phenotypes in patients with persistent asthma in a regular clinical setting. ClinicalTrials.gov identifier: NCT02026336. PMID- 26817139 TI - Longitudinal Validation of the Spanish Version of the Health-Related Quality of Life Questionnaire for Hymenoptera Venom Allergy (HRQLHA). AB - BACKGROUND AND OBJECTIVE: The Spanish version of the health-related quality of life questionnaire for allergy to hymenoptera venom (HRQLHA) has been shown to be reliable, internally consistent, and externally valid. The aim of this study was to complete the validation of the HRQLHA by analyzing its sensitivity to changes (longitudinal validity) using the sting challenge test (SCT) as the variable of change. PATIENTS AND METHODS: Patients over the age of 17 years with a systemic allergic reaction to Apis, Vespula, or Polistes venom were included during their first year of venom-specific immunotherapy. Patients were assigned to either a group that underwent the SCT or a control group that did not. All patients completed the HRQLHA at baseline and after a period of 2 to 4 months, during which time the SCT was performed in the active group, with no intervention in the control group. RESULTS: Fifty patients were included in the study: 25 in the SCT group and 25 in the control group. The patients in the SCT group showed a significant improvement in mean HRQLHA score (+0.35, P=.03) after the SCT, while those in the control group showed no significant changes in questionnaire scores. CONCLUSIONS: Our results demonstrate the sensitivity of the HRQLHA to changes and thus complete the longitudinal validation of the questionnaire. A well-tolerated SCT improves the quality of life of venom-allergic patients as it reduces anxiety associated with the fear of being stung. PMID- 26817141 TI - Proteins Responsible for Fruit allergies in the Northwest of Spain. PMID- 26817142 TI - Recurrent Anaphylaxis: A Case of IgE-Mediated Allergy to Carmine Red (E120). PMID- 26817143 TI - Allergic Reactions in Anesthesia: Do Diagnostic Studies Ensure the Safety of Reoperation? PMID- 26817144 TI - Fixed Drug Eruption Due to Mesna. PMID- 26817145 TI - Social Networks, Asthma and Much More... . PMID- 26817146 TI - Icatibant Exposure During Pregnancy in a Patient With Hereditary Angioedema. PMID- 26817147 TI - Description of Sunflower Seed-Fungus Syndrome. PMID- 26817148 TI - An Unusual Case of Contact Dermatitis to Vulcanization Additives. PMID- 26817149 TI - Cross-reactivity Between Cassava and Latex in a Colombian Patient With an Anaphylactic Reaction. PMID- 26817150 TI - [Community-based CKD study in Japan]. PMID- 26817151 TI - [Epidemiology of chronic kidney disease: the Hisayama Study]. PMID- 26817152 TI - [Epidemiology of albuminuria (proteinuria) and its role in clinical trials]. PMID- 26817153 TI - [Community-based CKD study in Japan]. PMID- 26817154 TI - [Chronic Kidney Disease Prognosis Consortium: achievements and future directions]. PMID- 26817155 TI - [The latest clinical research findings in the field of CKD-MBD]. PMID- 26817156 TI - [Clinical and epidemiological studies of kidney transplantation in Japan: a review of literature]. PMID- 26817157 TI - [Ethics and conflict of interest in clinical research: sociological view]. PMID- 26817158 TI - [Aberrant glycosylation and localization of polycystin-1 caused polycystic kidney in an AQP11 knockout model]. PMID- 26817159 TI - [Discovery of novel SPAK inhibitors that block WNK kinase signaling to cation chloride transporters]. PMID- 26817160 TI - [Kelch-like protein 2 mediates angiotensin II--With no lysine 3 signaling in the regulation of vascular tonus]. PMID- 26817161 TI - [Mechanism regulating mineralocorticoid receptor in the kidneys]. PMID- 26817162 TI - [CKD-MBD in all CKD stages: integration of basic and clinical research]. PMID- 26817163 TI - [Trends in international competitiveness of Japan's scientific research]. PMID- 26817164 TI - [IgA nephropathy]. PMID- 26817165 TI - [Polycystic kidney disease]. PMID- 26817166 TI - [Diabetic nephropathy]. PMID- 26817167 TI - [A case report of hepatitis B virus reactivation in a hepatitis B core antibody positive, hepatitis B surface antigen-negative hemodialysis patient]. AB - Reactivation of the hepatitis B virus (HBV) has been reported in patients receiving immunosuppressive therapy or chemotherapy. We report a case of HBV reactivation in a patient negative for hepatitis B surface antigen (HBsAg), positive for hepatitis B core antibody (anti-HBc), and positive for hepatitis B surface antibody (anti-HBs), who was undergoing chronic maintenance hemodialysis without immunosuppressive therapy or chemotherapy. The patient was an 85-year-old woman with end-stage renal disease due to nephrosclerosis who had undergone maintenance hemodialysis for a year. She had been HBsAg-negative, anti-HBc- and anti-HBs-positive previously, but biannual routine surveillance for HBV showed positivity for HBsAg, negativity for anti-HBs, and positivity for HBV DNA (5.9 log copies/mL). She was asymptomatic, and transaminases were within normal limits. She was dialyzed in an isolated room with a dedicated staff member for the control of infection. HBV is a blood-borne pathogen, which is highly infectious. Hemodialysis is a procedure associated with high risk for blood-borne infection. We should recognize the risk of reactivation of HBV in HBsAg-negative, anti-HBc-positive patients, and consider how to incorporate anti-HBc screening and infection control in isolated anti-HBc-positive hemodialysis patients in clinical practice. PMID- 26817168 TI - [Merkel cell carcinoma of the ear lobe complicated with nephrosis syndrome and malignant lymphoma: a case report]. AB - Here we report a rare case of Merkel cell carcinoma complicated with nephrosis and malignant lymphoma. A 79-year-old male, who had undergone rectectomy due to colorectal cancer about 10 years previously, was diagnosed as Merkel cell carcinoma of the left ear lobe with lymph node metastases. Tumor resection and lymph node dissection were performed. A year later, follow-up PET-CT revealed a small hot spot at the ileocecum without apparent tumor formation based on examination by colonoscopy. The patient received 56 Gy of radiation. Two months later, he developed new-onset nephrosis followed by renal failure, and was referred to our hospital (Cr 4.26 mg/dL, UA 13.5 mg/dL, Alb 2.1 g/dL). Further examination negated the possibility of vasculitis, collagen disease, or myeloma kidney. Since his renal function continued to decline, causing uremic symptoms, he was hospitalized and underwent hemodialysis soon after referral. Abdominal CT scan revealed an ileocecal mass with multiple abdominal lymphadenopathy, which was later diagnosed as diffuse large B-cell lymphoma (stage IV) by tumor biopsy. Corticosteroid therapy (prednisolone 60 mg/day) was soon initiated with no response. Local skin redness and blister formation at the left shoulder emerged gradually, which strongly suggested a local recurrence of Merkel cell carcinoma. Despite the use of rituximab, the patient's general condition deteriorated without any sign of recovery. Three months after the start of dialysis, we discontinued dialysis therapy due to his poor health status, and eventually he died of cachexia. Autopsy revealed triple cancers: rectal cancer, Merkel cell carcinoma, and malignant lymphoma. In addition to the case report, we will summarize and discuss former similar case reports in the literature. PMID- 26817169 TI - African American Clergy and Depression: What they know; What they want to know. AB - Nearly 40% of African Americans use clergy as their primary source of help with depression. However, less than half of African American clergy are trained in counseling. OBJECTIVES: 1) to examine how African American cler recognize depression and 2) identify what they need to more effectively identify and address depression in their congregants. DESIGN: This was a descriptive, quantitative study using a Personal Profile Questionnaire and a Mental Health Counseling Survey. RESULTS: Sixty-five clergy completed the data collection tools; approximately 50% had some training in counseling. The majority could identify signs of depression. Eighty-one percent stated they needed additional education about depression and access to referral resources. CONCLUSIONS: If clergy take an active role in addressing the issue of depression and establishing liaisons with mental health professionals the stigma associated with depression could be greatly reduced, and individuals might enter into treatment earlier thus improving their quality of life. PMID- 26817170 TI - HIV Prevention, Stigma, and Care in Ho Chi Minh City and Da Lat Vietnam. AB - PURPOSE: A four-week interdisciplinary student/faculty research project in Vietnam served as a focused experience in understanding Vietnamese healthcare structures, functions, outcomes. DESIGN: Testing the validity and feasibility of a successful US HIV intervention program called Women's Voices Women's Lives(c) using group and individual interviews. FINDINGS: Healthcare inequities and poverty were found to paralyze individual, family, and community mobilization in HIV testing while stigma is a key barrier to both testing and care seeking. IMPLICATIONS: Vietnam has become a place where living with HIV infection challenges communities in a distinct socio-cultural context while incidence and prevalence rates continue to rise. PMID- 26817171 TI - Individual, Programmatic, and Institutional Influences on Undergraduate Athletic Training Students' Cultural Competence. AB - This study sought to determine factors that influence an undergraduate athletic training student's (ATS) level of cultural competence (CC). Utilizing a CC score derived from a student survey, one-way ANOVAs to identify differences in CC scores by gender, race, and year in school and three separate correlation analyses (all students, Caucasian Students, Students of Color) to identify the relationship between CC and variables were performed. Only eight variables in the Students of Color model were significant. This suggests that race may impact factors that influence an ATS CC and could assist educators to recognize uncontrollable factors may influence students' CC. PMID- 26817172 TI - Recruitment of Asians and Pacific Islanders with Type 2 Diabetes into a Clinical Research Trial of Enhancing Diabetes Self-Management. AB - The objective of the study was to evaluate strategies and barriers to recruiting Asians and Pacific Islanders (API) with type 2 diabetes, into clinical trials. Descriptive statistics and content analysis were utilized to analyze reasons for non-participation. A "talk story" interview method was employed to recruit participants and uncover reasons for non-participation. A total of 1891 potential participants were identified and 340 declined participation. Eighty who declined were randomly selected to provide their reasons for non-participation. Socioeconomic issues faced by this population, such as earning wages to meet basic needs and care giving took precedence over altruistic participation in research. PMID- 26817173 TI - Measuring the Cross-Cultural Adaptability of a Graduate Student Team from a Global Immersion Experience. AB - BACKGROUND: Cultural competency skills for health and human services providers is important because of the growing diverse populous. Experiential learning through global immersion may promote these skills. METHODS: Using a non-randomized cohort design, there were two groups of unmatched graduate students. One reviewed an online educational module and participated in campus activities and an experience in Malawi; the other reviewed the module only. The students were assessed pre- and post-immersion using a measure of cross-cultural adaptability, a component of cultural competency skills. RESULTS: Comparing total scores on the Cross-Cultural Adaptability Inventory (CCAITM), pre-immersion (baseline), there was no significant difference between the groups. Comparing both groups' total scores pre/post-immersion, there was a significant difference. There was a significant difference for the experimental group between the pre/post-immersion total scores but not for the control group. Comparing both groups'post immersion, there was a significant difference between the groups. Comparing both groups' component scores, there was a significant difference in the Emotional Resilience and Perceptual Acuity variables for the experimental group but not for the control group. Comparing both groups' component scores, there was no significant difference in the Personal Autonomy and Flexibility Openness variables. CONCLUSION: Participation in a 6-week global immersion experience compared to education only made a greater change in the development of cross-cultural adaptability for a graduate student team. PMID- 26817174 TI - Cultural Self-Efficacy of Second- Degree Nursing Students in Providing Care to Immigrants. AB - The purpose of this study was to determine the levels of perceived cultural self efficacy of senior students in second-degree pre-licensure nursing programs in the provision of culturally appropriate care to immigrants. The study employed a quantitative, non-experimental design with survey methodology. The convenience sample consisted of 117 senior students enrolled in accelerated bachelor of sciences in nursing and entry levels master of sciences programs. The study used Bernal and Froman's Cultural Self-Efficacy Scale (CSES). The study found that the participants had low levels of transcultural self-efficacy. There was no association between the participants' demographic characteristics and their CSES scores. These findings were consistent with the findings of previous studies that surveyed traditional nursing students. The study provided important assessment data on learning needs of second-degree nursing student concerning the provision of culturally congruent care. PMID- 26817175 TI - Comparative Study of the Effects of Tamoxifen Citrate and Folate on Semen Quality of the Infertile Male with Semen Abnormality. AB - OBJECTIVE: To assess the effect of treatment with a combination of the antiestrogen Tamoxifen citrate and Folate on semen quality of the infertile male with semen abnormality. DESIGN: Prospective randomized controlled trial study. MATERIAL AND METHOD: Between May 2013 and October 2014, 68 infertile male with semen abnormality were asked to join the present study. Informed consents were signed; all patients were divided into four groups, given placebo (control), Tamoxifen citrate 20 mg/day, Folate 5 mg/day, and Tamoxifen citrate plus Folate for continuous three months. The result of treatments i.e., semen parameters, hyaluronan binding assay, hypo-osmotic swelling test, and DNA damage test were evaluated at baseline, at the end of drugs treatment (3-month), and at 3-month after discontinuation of treatment (6-month). RESULTS: Tamoxifen alone caused a significant increase in sperm concentration, while Tamoxifen plus Folate significantly increased both sperm concentration and sperm motility at 3-month after treatment. Folate alone and Tamoxifen plus Folate significantly decreased DNA tail length at 3-month and at 3- and 6-month after treatment, whereas Tamoxifen alone caused no significant change in DNA tail length. Sperm DNA integrity was improved as seen by decrease in the length ofDNA tail. CONCLUSION: Our study indicated that Folate in combination with Tamoxifen citrate could improve sperm quality including semen parameters and sperm DNA integrity. PMID- 26817176 TI - Reliability of Thai-Version Overactive Bladder Symptom Scores (OABSS) Questionnaire and the Correlations of OABSS with Voiding Diary, International Prostate Symptom Score (IPSS), and Patient Perception of Bladder Condition (PPBC) Questionnaires. AB - BACKGROUND: Overactive bladder (OAB) is defined by subjective symptoms such as urgency, frequency, and urge incontinence, rather than objective measures. Using questionnaires like OABSS can help in diagnosis and evaluation of patients'symptoms for further assessment. OBJECTIVE: To evaluate test-retest reliability of OABSS in 2-week interval and to evaluate the correlation of OABSS with voiding diary, IPSS, and PPBC. MATERIAL AND METHOD: Between August 2009 and January 2011, 56 Thai women aged more than 18 years, attending urogynecology clinic at King Chulalongkorn Memorial Hospital were recruited in the study. They were diagnosed as having the overactive bladder with these criteria, symptoms of urinary frequency, urgency with or without urge incontinence, for more than three months, and at least one episode of urgency with or without incontinence in last three days. After giving the written informed consents, the patients were instructed to complete the voiding diary before starting the study and at the second visit (two weeks apart). The Thai version of self-answered questionnaires (OABSS, IPSS, and PBC) were also given at 0- and 2-week visit. The questionnaires were translated by one linguist from the Language Institute, Chulalongkorn University, Thailand, and translated back by another linguist to English. The content and language validity were checked by one urogynecologist at our department. The study was conducted after the protocol was approval by the Institutional Review Board (IRB). RESULTS: The test-retest reliabilities (intraclass correlation) of the OABSS, PPBC, and IPSS total score were 0.88, 0.44, and 0.85. The overall Cronbach's alpha of OABSS was 0.31 and 0.41 at 0- and 2-week respectively. CONCLUSION: Thai version of OABSS was reliable, valid, and related to the abnormal voiding symptoms. Further use of Thai version OABSS questionnaire was advocated for both clinical study and clinical practice in Thai women with OAB. PMID- 26817177 TI - The Number of Infant Feeding Positions and the 6-Month Exclusive Breastfeeding Rates. AB - BACKGROUND: Appropriate infant feeding positions will help with latching. Good latching will help decrease cracked nipple and complication leading to early breastfeeding cessation. OBJECTIVE: To investigate the association of the number of infant feeding positions on exclusive breastfeeding during the first six months postpartum period. MATERIAL AND METHOD: The subjects were primiparous women who delivered without complications and intended to breastfeed their newborns at least six months at the HRH Princess Maha Chakri Sririndhorn Medical Center in Nakhon Nayok Province, Thailand, between May 2012 and April 2013. On the first day postpartum, the mothers had received instructions on four infant feeding positions. These included the cradle, cross cradle, football carry, and side-lying positions, and all were practiced. The mothers were assessed on their use of the numbers of infant feeding positions at the second day postpartum prior to their discharge. Telephone follow-ups at the second, fourth, and sixth month postpartum periods were collected and used for exclusive breastfeeding data collection following discharge. Demographic data and exclusive breastfeeding rates were analyzed by Chi-square test, one-way ANOVA test, and relative risk with a 95% confidence interval (CI). RESULTS: Five hundred forty five primiparous women were enrolled in the present study. The data showed that the 6-month exclusive breastfeeding rates of the studied group who could breastfeed by one, two, three, and four positions, had statistically signifcant differences (p-value < 0.05). The relative risks for exclusive breastfeeding rates between the mothers who used two infant breastfeeding positions or more and the mothers who used only one position were 1.68 (95% CI 1.45-1.95) at the 2-month, 1.69 (95% CI 1.38-2.09) at the 4-month, and 1.51 (95% CI 1.18-1.94) at the 6-month postpartum periods. CONCLUSION: The number of infant breastfeeding positions had an association with the exclusive breastfeeding rates during the six months postpartum period. PMID- 26817178 TI - Inter- and Intra-Observer Reliability of Modified Rodnan Skin Score Assessment in Thai Systemic Sclerosis Patients: A Validation for Multicenter Scleroderma Cohort Study. AB - BACKGROUND: Assessment of the severity of skin tightness by the modified Rodnan skin score (mRSS) for systemic sclerosis (SSc) has been found feasible, valid, and reliable. Despite being a major clinical outcome, it has not yet been validated by Scleroderma Research Group. OBJECTIVE: To (a) determine the inter observer variability vis-a-vis mRSS assessment by members ofthe Scleroderma Research Group before and after mRSS-assessment training by an experienced rheumatologist and (b) determine intra-observer variability. MATERIAL AND METHOD: Between June and August 2013, we conducted a descriptive study of Thai adult SSc patients and all rheumatologists in the Scleroderma Research Group at Srinagarind Hospital, Khon Kaen University, Northeast Thailand. Eleven rheumatologists assessed the mRSS of 22 SSc patients three times (i.e., before and after training, and eight weeks after training). The intra-class correlation coefficient (ICC) and its 95% CI were estimated at week 8 after training. RESULTS: The mean and standard deviation (SD) of mRSS for inter-observer variability analysis was slightly decreased from before training, after training (by an experienced rheumatologist), and at week 8 after training (17.3 +/- 11.9, 16.5 +/- 11.1, and 16.2 +/- 10.3, respectively). Intra-observer variability had moderate agreement before training (ICC 0.59; 95% CI 0.38-0.78), which increased to good agreement after training and at week 8 after training (ICC 0.60; 95% CI 0.42-0.76 vs. 0.68; 95% CI 0.53-0.82, respectively). CONCLUSION: Inter-observer variability for mRSS assessment decreased after training and the reduction persisted for eight weeks after training. The ICC rose from moderate agreement at baseline to good agreement at the end of the study. The mRSS assessment by members of the Scleroderma Research Group was reliable. PMID- 26817179 TI - Blood Volume Monitoring to Assess Dry Weight in Pediatric Chronic Hemodialysis Patients. AB - OBJECTIVE: Volume overload from an incorrect assessment of dry weight leads to cardiovascular diseases in chronic hemodialysis patients. Dry weight assessment in pediatric is difficult for a number of reasons including growth. Blood volume monitoring (BVM) has been proposed as an accurate method of estimating dry weight in adult. However, there is very scant data regarding B VM assessment in pediatric. Therefore, the authors conducted a study to compare dry weight, postdialytic body weight, predialytic blood pressure, intradialytic blood pressure, and intra dialytic symptoms between clinical adjustment and B VM method. MATERIAL AND METHOD: In pediatric chronic hemodialysis patient, B VM was performed to guide ultrafiltration to adjust dry weight compared with clinical adjustment. Data including dry weight, postdialytic body weight, predialytic blood pressure, intradialytic hypotension, and intradialytic symptoms were analyzed over each 1-month period of treatment course. RESULTS: Ten patients (5 males/5 females, age 16.55 +/- 2.49 years) were enrolled. Comparing clinical adjustment to assess dry weight with BVM, there were no differences in dry weight (38.38 +/- 7.43 vs. 38.12 +/- 7.58 kg) and postdialytic body weight (38.54 +/- 7.61 vs. 38.23 +/- 7.35) of both methods. Dry weight adjusted by clinical adjustment trends to higher than by BVM (0.14 +/- 0.46 vs. -0.26 +/- 0.57 kg). There is also no difference between predialytic blood pressure of both methods. There is no intradialytic hypotension during the study period. However, intradialytic symptoms in clinical adjustment diy weight is more frequent than B VM method, especially thirst. CONCLUSION: The use of BVM tends to decrease dy weight in pediatric chronic hemodialysis patients. Even though, no difference in predialytic blood pressure and intradialytic hypotension. BVM to assess dry weight reduces abnormal intradialytic symptoms, especially thirst. Sofar there is no gold standard to access the accurate dry weight in children. PMID- 26817180 TI - Intra-Abdominal Infections: Prevalence and Risk Factors of ESBLs Infections. AB - BACKGROUND: Extended-Spectrum Beta-Lactamases (ESBLs)-producing bacteria are increasing challenge in the treatment of both community acquired and nosocomial intra-abdominal infections (IAIs). Investigating the characteristics ofpatients with the IAIs caused by ESBL-producing bacteria and assessing the risk factors of ESBLs infection will lead to appropriate therapeutic management. OBJECTIVE: To determine prevalence of ESBL-producing bacteria in IAIs in Phramongkutklao Hospital and identify risk factor of the ESBL-infections. MATERIAL AND METHOD: We performed a retrospective cross sectional study ofpatients admitted in Phramongkutklao Hospital between January 1 and December 30, 2012 to determine the prevalence and risk factors acquiring ESBL-producing bacteria in IAIs and the outcomes of these infections. RESULTS: Sixty-one patients were studied, of whom 45 (73.8%) had community-acquired and 16 (26.2%) had nosocomial IAIs. ESBL producing bacteria were positive in 18 patients, 7 (15.6%) in community acquired and 11 (68.8%) nosocomial infection. The common gram negative bacilli were Escherichia coli, Klebsiella pneumoniae. Univariate analysis showed three factors including nosocomial infection, prior admission within one month, and prior use of antibiotics, in particular, cephalosporin, and beta-lactam/beta-lactamase inhibitor (BLBI), to be associated with ESBL-producing bacterial infections. In the multivariate analysis, nosocomial infection (odds ratio [OR], 5.26; 95% confidence interval [CI], (1.07-25.88); p = 0.041) was independent factor that related to the ESBL-infection in IAIs. CONCLUSION: Nosocomial infection was found as an independent factor significantly associated with ESBL-infection in IAIs. Other critical issues remain debatable and more controversial are due to the limited number of the study's patients. PMID- 26817181 TI - An Equivalence Trial Comparing Labetalol and Diltiazem in Controlling Emergence Hypertension after Supratentorial Tumor Surgery. AB - BACKGROUND: Hypertension and tachycardia during emergence from anesthesia for craniotomy could increase risks of cerebral complications. Several anesthetic, sedative, and antihypertensive drugs have been suggested that may be successful at suppressing these unwanted hemodynamic consequences. OBJECTIVE: To study the equivalent efficacy and side effects of two antihypertensive drugs, diltiazem and labetalol. MATERIAL AND METHOD: A block randomized control trial was performed in 184 patients who developed emergence hypertensive response after craniotomyfor supratentorial tumor removal. Systolic blood pressure (SBP) of each patient was suppressed by 2.5 mg of study drugs and repeated with fix dosage of 2.5 mg every two to three minutes to maintain SBP lower than 140 mmHg with a cumulative dose within 20 mg. Data regarding demographic, successful rate in controlling hypertension, drug dosage, and incidence of side effects were analyzed. RESULTS: The success rate of treatment of labetalol was equivalent to diltiazem (87.1% and 80.2% respectively) [p = 0.003, 95% CI = 6.88 (-2.06 to 15.8)]. There was no statistical significant difference on dosage of drugs used or incidence ofside effect (hypotension, bradycardia, heart block, and bronchospasm). Median (minimum maximum) dosage of labetalol and diltiazem were 10 mg (2.5-20 mg) and 10 mg (2.5 20 mg) respectively. The expense for labetalol was 1/6 of diltiazem. CONCLUSION: Labetalol has equivalent efficacy to diltiazem. Both drugs used low median dosage giving low incidence of side-effects. Labetalol is a good alternative drug to control hypertensive response during emergence from anesthesia for post craniotomy. PMID- 26817182 TI - Comparison of Accuracy in Intraocular Lens Power Calculation by Measuring Axial Length with Immersion Ultrasound Biometry and Partial Coherence Interferometry. AB - OBJECTIVE: To re-examine relative accuracy of intraocular lens (IOL) power calculation of immersion ultrasound biometry (IUB) and partial coherence interferometry (PCI) based on a new approach that limits its interest on the cases in which the IUB's IOL and PCI's IOL assignments disagree. MATERIAL AND METHOD: Prospective observational study of 108 eyes that underwent cataract surgeries at Taksin Hospital. Two halves ofthe randomly chosen sample eyes were implanted with the IUB- and PCI-assigned lens. Postoperative refractive errors were measured in the fifth week. More accurate calculation was based on significantly smaller mean absolute errors (MAEs) and root mean squared errors (RMSEs) away from emmetropia. The distributions of the errors were examined to ensure that the higher accuracy was significant clinically as well. RESULTS: The (MAEs, RMSEs) were smaller for PCI of (0.5106 diopter (D), 0.6037D) than for IUB of (0.7000D, 0.8062D). The higher accuracy was principally contributedfrom negative errors, i.e., myopia. The MAEs and RMSEs for (IUB, PCI)'s negative errors were (0.7955D, 0.5185D) and (0.8562D, 0.5853D). Their differences were significant. The 72.34% of PCI errors fell within a clinically accepted range of +/- 0.50D, whereas 50% of IUB errors did. CONCLUSION: PCI's higher accuracy was significant statistically and clinically, meaning that lens implantation based on PCI's assignments could improve postoperative outcomes over those based on IUB's assignments. PMID- 26817183 TI - The Difference of Treatment Results between Botulinum Toxin A Split Injection Sites and Botulinum Toxin A Non-Split Injection Sites for Hemifacial Spasm. AB - OBJECTIVE: To compare hemifacial spasm treatment results between Botulinum toxin A split injection sites and Botulinum toxin A non-split injection sites. MATERIAL AND METHOD: Thirty-one hemifacial spasm patients were randomly assigned into the non-split injection sites group (injecting Botulinum toxin A to the zygomaticus major and risorius each) or split injection sites group with the same amount of Botulinum toxin A as the first method (injection Botulinum toxin A to the zygomaticus major and minor and risorius two injections each) The main outcomes are onset of improvement and effective duration of treatment. RESULTS: Fifteen patients were assigned to non-split injection sites group and 16 patients were assigned to split injection sites group. The median onset of improvement in non split injection sites group and split injection sites group was 4.0 and 4.5 days, respectively (p = 0.984). The effective duration of treatment in the non-split injection sites group was 60.0 days and in the split injection sites group was 54.5 days (p = 0.582). CONCLUSION: The splitting of injection sites did not signicantly improve the efficacy of Botulinum toxin A in the treatment of hemifacial spasm. PMID- 26817184 TI - Comparison between Different Methods of Monofilament Test in Multibacillary Leprosy. AB - BACKGROUND: Leprosy or Hansen's disease predominantly affects skin and peripheral nerves; therefore, can cause visible deformities from sensory and motor impairment. Early detection of sensory deficit has been of great benefit in a vigorous preventive role. OBJECTIVE: To compare the result of sensory evaluation in multibacillary leprosy (AB) patients using Semmes-Weinstein monofilament (SWM) and conventional monofilament technique used in Thailand and to observe the course of neuritis detected during the study period MATERIAL AND METHOD: MB patients from Hansen's clinic at the Department of Dermatology, Siriraj Hospital, and Leprosy clinic at Raj Pracha Samasai Institute were evaluated for sensory impairment using monofilament test by both SWM and conventional technique for two consecutive follow-up visits. The patients'demographic data, clinical and laboratory findings, and course of disease were recorded RESULTS: Seventy MB patients were enrolled Two-third of the patients were male (71.4%) and a mean (SD) age was 43 (15.75) years with a range of 19 to 85-years-old. The results from SWM and conventional Thai technique were not statistically different for ulnar median, and posterior tibial nerve distribution excluding heel area (p = 1.00). Twenty-eight (40%) patients who mentioned of numbness at either palms or soles had impaired sensation detected by SWMtechnique (p = 0.014). CONCLUSION: Using SWMwith less tested points can minimize the time spent on sensory evaluation in MB patients; hence, we encourage the application of the present SWM technique to shorten the time in each follow-up visit and to improve the follow up practice for better services of leprosy patients in Thailand. PMID- 26817185 TI - Diagnosis of Xp11.2 Translocation Renal Cell Carcinomas in the Thai Patients. AB - BACKGROUND: Xp11.2 translocation renal cell carcinomas (TRCCs) are rare tumors recently accepted as a separated tumor type in 2004 WHO classification. To diagnose these tumors, histological recognition and confirmation of translocation are necessary. While the incidence of overall renal cell carcinomas (RCCs) is increased after the age of 40, Xp11.2 TRCCs are predominantly reported in young patients. The incidence of these tumors in Thailand has not been evaluated. OBJECTIVE: To identify the frequency of Xp11.2 TRCCs, clinical presentation and follow-up information in 40 year-old or younger patients by using TFE3 immunostaining to confirm the translocation. MATERIAL AND METHOD: All cases of 0- to 40-years-old patients diagnosed as RCCs from nephrectomy specimens between 2001 and 2011 at Siriraj Hospital were reviewed by one pathology resident and two pathologists. Immunohistochemical staining for TFE3 was performed on cases morphologically suspected for TRCC or showing unusual histology. RESULTS: Four cases consistent with Xp11.2 TRCC were identified by TFE3 immunostaining from all 31 cases (12.9%). Three cases were females and one was male. Two cases were at stage 4 and passed away several months after the operation. The other two patients were at stage 2. One patient is alive without recurrence for at least 36 months after surgery alone. The other died from underlying SLE. CONCLUSION: TFE3 immunostaining is a useful andpractical toolfor screening and diagnosis of Xp11.2 TRCCs, but staining results can be difficult to interpret. Thus, genetic analysis is still necessary especially when immunostaining shows problematic result. Fresh tumor tissue sampling in all young patients is recommended in case of further genetic studies needed. PMID- 26817186 TI - Outcomes of Short-Course Inpatient Stroke Rehabilitation Program in Tertiary Hospital: A Pilot Study. AB - BACKGROUND: Stroke is one of the most common cause of disabilities in Thailand. Full-course comprehensive rehabilitation to achieve maximum goalfor each patient was uncommon in secondary and tertiary hospitals because of limited resources and budget, so short-course inpatient stroke rehabilitation program was developed for service in these circumstances. OBJECTIVE: To evaluate the efficiency and cost of the short-course inpatient stroke rehabilitation in Maharat Nakhon Ratchasima Hospital. MATERIAL AND METHOD: This prospective study included stroke patients with aged over 18 years old, able tofollow one-step command and admitted in rehabilitation ward for short-course rehabilitation program between January 1 and December 31, 2014. Patient's characteristic data, Barthel Index (BI) scores, BI effectiveness, BI efficiency, length of stay (LOS), Thai HospitalAnxiety and Depression Scale (THAI HADS), WHOQOL-BREF-THAI, cost, and details oftraining were recorded RESULTS: Fifty stroke patients were included in the present study. The mean interval from onset of stroke to admission for this program was 29.9 days (1 143, SD 31.18). The mean age was 57 years (19-86, SD 12.7). Seventy-two percent of cases were ischemic stroke. The impairments of the patients were hemiparesis (100%), aphasia (36%), dysarthria (32%), incontinence (14%), cognitive problem or neglect (12%), and dysphagia (10%). The mean LOS was 9.38 days (3-27, SD 5.31). Mean BI score on admission and at discharge were 8.12 (0-18, SD 4.52) and 13.12 (2-20, SD 4.28). The mean of BI score change was 5 (2-10, SD 2.25): The BI efficiency was 0.56 points/day. Eight cases (22%) had anxiety and 10 cases (28%) had depression. The mean total cost was 7,729 baht (1,828-22,450, SD 4,330) or about 240 US dollar CONCLUSION: The short-course inpatient rehabilitation program could improve functional ability in stroke patients with low cost but high efficiency. This program is suitable for subacute stroke patients in hospitals with limited resources and budget. PMID- 26817187 TI - Bisphosphonate Therapy for Refractory Langerhans Cell Histiocytosis: A Case Report. AB - Although patients diagnosed as Langerhans cell histiocytosis (LCH) with bone lesion initially respond well to treatment, some may experience relapse or refractory disease. Pamidronate, a potent N-bisphosphonate, has been used in several primary bone diseases, benign bone tumors, and metastatic bone cancers. The mechanism includes an inhibitory effect on osteoclast activity by decreasing development and recruitment of osteoclast progenitors and promoting osteoclast apoptosis. Herein, we introduce a seven-month-old Thai girl who was diagnosed as multiple-relapse LCH with refractory bone lesions and was treated with standard and salvage steroid-based therapies. After receiving two courses of intravenous pamidronate, she had marked clinical and radiographical improvement without any adverse events. She has been in remission for two years after receiving six courses of therapy. This report supports the efficacy ofpamidronate in LCH related bone lesions, but further studies in large cohort are warranted. PMID- 26817188 TI - Isolated Ocular Relapse in Childhood Acute Lymphoblastic Leukemia during Second Interim Maintenance Phase of Chemotherapy: Case Report. AB - More than 80% of acute lymphoblastic leukemia (ALL) in pediatric population is curable by using combinations of chemotherapy. However, 20% of the cases still suffer from disease relapse. The most common site of relapse is bone marrow. Relapse of childhood ALL involving the eyeball is rare. However, it occurs in 2.2% of relapsing children. The authors described a 10-year-old Thai boy with underlying ALL on therapy, presented with a one-month history of progressive visual loss of his right eye. The clinical and imaging studies strongly suggested the diagnosis of isolated ocular relapse. In this report, the authors presented the findings from successfully specific treatment consisting of systemic chemotherapy and radiation therapy on the affected eye. From other studies, the outcome was more favorable in cases of ocular relapse off therapy. In our study, one case of isolated ocular relapse ALL was reported. PMID- 26817189 TI - Nurses: The Backbone of Health Services. PMID- 26817190 TI - Caring is Serious Business. PMID- 26817191 TI - "Take the Scare Out of Care" FNA's Campaign to End Violence Against Nurses. PMID- 26817192 TI - Substance Use Disorder: Intervention Project for Nurses. PMID- 26817193 TI - Caring Holistically for Patients is More Than a Platitude. PMID- 26817195 TI - Physicians share the value found from their AMS Membership. PMID- 26817194 TI - Dementia. PMID- 26817196 TI - Switching Gears and the Golden Rule. PMID- 26817197 TI - Letter to the Editor. PMID- 26817198 TI - Connecting More than Flesh and Bone. State's First Primary Care Sports Medicine Fellowship Promotes Athletics & Community. PMID- 26817199 TI - Dupuytren's Disease. PMID- 26817200 TI - Dental School Could Fill a Cavity in Arkansas' Health System. PMID- 26817201 TI - FIBROVASCULAR POLYP: AN UNUSUAL MASS IN THE ESOPHAGUS CAUSING DYSPHAGIA. AB - We present a case of a 56-year-old Caucasian women with long-standing gastroesophageal reflux disease complicated with non-dysplastic Barrett's esophagus and stricture presented with difficulty in swallowing. PMID- 26817202 TI - Introduction to the Arkansas Center for Respiratory Technology Dependent Children. PMID- 26817204 TI - Mastalgia: Characteristics and Associated Factors in Thai Women. AB - OBJECTIVE: This study aimed to identify the clinical presentation, natural history, severity and associatedfactors in Thai women presented with mastalgia. MATERIAL AND METHOD: One hundred and five Thai women with breast pain who visited HRH Princess Maha Chakri Sirindhorn Medical Center were interviewed with breast pain. The data about socio-economic status, sign and symptoms of breast pain, associated factors, mental status and quality of life at first presentation and 6 12 months afterward were collected. RESULTS: In 105 Thai women who present with mastalgia, the pain was associated with menstrual cycle, around 70 percents. Both cyclic and non-cyclic mastalgia patients had similar characteristics as type, intensity and location. There were no diferences in caffeine and high-fat food intake between mild and severe mastalgia. In twenty-seven percent ofpatients who had severe breast pain, the pain affected their work, sleeping and daily entertainment. Though the pain did not influence mental status, it affected some part of quality of life such as apart of bodily pain, socialfunction and mental health. At second follow-up, 80 patients had decreased severity and intensity of pain. The mental status and quality of life evaluations were statistically significant. CONCLUSION: The results showed that most mastalgia was associated with menstruation. Diet showed no definitive association with breast pain severity and severe mastalgia influenced patients' daily activity and quality of life. PMID- 26817203 TI - Prevalence of Cigarette Smoking and Associated Risk Factors amongst Middle-School Students in Ongkharak District, Thailand. AB - BACKGROUND: Cigarette smoking is a common tobacco use which is the leading preventable cause of death in Thailand. Prevalence and risk factors of cigarette smoking are varied amongst communities. OBJECTIVE: The present study aimed to determine the prevalence and associated risk factors of cigarette smoking amongst middle-school students studying in the Ongkharak district, central Thailand. MATERIAL AND METHOD: A cross-sectional survey was conducted with students of the public schools in Ongkharak district, central Thailand, in 2013. Of 677 middle school students (grade 7-9) who currently enrolled in the classes, 130 were randomly selected. Data on smoking as well as demographic characteristics were collected using an anonymous self- administered questionnaire which was modified from the 2013 Middle School Youth Risk Behavior Survey (YRBS) and translated into Thai. RESULTS: The prevalence of children who smoked or had smoked before was 24.6% (38.9% amongst males and 6.9% amongst females, p-value < 0.001), of this proportion 50% were current smokers. Logistic regression analysis showed that the risk factors for having ever smoked were being male (OR = 7.63, 95% CI 2.26 26.90), of an older age (OR = 2.30, 95% CI 1.40-3.76), high coffee or tea consumption (OR = 2.95, 95% CI 1.08-8.05) and sharing a household with a smoker (OR = 2.96, 95% CI 1.09-8.06). Those who have smoked reported higher prevalence of asthma compared to those who have never smoked (25.0% vs. 9.2%, p-value = 0.033). CONCLUSION: About a quarter ofmiddle-school students in Ongkharak district smoked cigarettes. Anti-smoking and prevention policies should be encouraged to tackle this rising major public health problem. PMID- 26817205 TI - Estrogen Increases Striatal GDNF Immunoreactivity with no Effect on Striatal FGF 2 Immunoreactivity of MPTP-Treated Mice. AB - BACKGROUND: Glial derived neurotrophic factor (GDNF) and basic fibroblast growth factor (FGF-2) protect nigrostriatal dopaminergic (DA) neurons and their projections in animal models of Parkinson's disease (PD). Recent data indicate neuroprotective effects of estrogen in PD animal models through its anti inflammatory and anti-oxidative effects, yet the hormonal effects on GDNF and FGF 2 expression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice remain uninvestigated. OBJECTIVE: To determine the effects of 17 beta-estradiol (E2) on DA innervation and the expression ofGDNFandFGF-2 in the striatum of MPTP treated mice. MATERIAL AND METHOD: Adult male mice were treated with E2 or vehicle for 11 days during which they were injected with MPTP or saline on the sixth day. The striatum was collected on day 11 and processedfor tyrosine hydroxylase (TH), GDNF and FGF-2 immunohistochemistry. Extent ofDA innervation and the expression of GDNF and FGF-2 in the striatum were assessed by measuring optical density of TH, GDNF and FGF-2 immunoreactivity, respectively. RESULTS: MPTP induced loss of DA axons and upregulation of FGF-2 expression, but did not alter GDNF level. E2 alleviated loss of DA axons, increased GDNF level, yet caused no change in FGF-2 level ofthe MPTP-intoxicated animals. CONCLUSION: One possible mechanism by which E2 protects nigrostriatal DA axons against MPTP is through upregulation ofstriatal GDNF. PMID- 26817207 TI - Isoflavone Genistein Modulates the Protein Expression of Toll-like Receptors in Cancerous Human Endometrial Cells. AB - OBJECTIVE: The present study aimed to investigate whether genistein, a potent phytoestrogen mainly found in soybean, modulated the expression of TLRs 2, 3, 4 and 9 proteins in human endometrial epithelial cell line RL95-2 under basal and polyinosinic-polycytidylic acid (poly I: C) stimulated conditions to mimic viral infection. The genistein effects were also compared with 17beta-estradiol. MATERIAL AND METHOD: The RL95-2 cells were cultured in the estrogen-deprived media with or without poly I: C 30 min prior to incubation with genistein (10( 7), 10(-6) or 10(-5) M) or 17beta-estradiol (10(-9) M) for 48 h. The TLRs protein expression was analyzed by semi-quantitative Western blot. RESULTS: The cells expressed TLRs 3, 4 and 9 but a very low level of TLR2 proteins. Poly I: C significantly increased the TLRs 2 and 9 protein expressions whereas the TLRs 3 and 4 were reduced. Under basal condition, genistein at 10(-7) M increased the TLR2 while 17beta-estradiol decreased the TLR4. All concentrations of genistein and 17beta-estradiol attenuated the poly I: C induced increase in the TLR2. By contrast, both genistein at 10(-5) M and 17 beta-estradiol further potentiated the TLR4 suppressed by poly I: C. Only 17beta-estradiol was found to antagonize the poly I: C-induced changes in TLRs 3 and 9. CONCLUSION: Taken together, the present results that genistein increased the basal TLR2 and attenuated the viral component-induced TLR2 protein expression in human endometrial epithelial cells may indicate the potential role of this soy isoflavone in promoting the uterine immune function and probably alleviating the inflammation of endometrium following pathogen PMID- 26817206 TI - The Effects of Oral Vitamin D Supplement on Atopic Dermatitis: A Clinical Trial with Staphylococcus aureus Colonization Determination. AB - BACKGROUND: An increase in Staphylococcus aureus skin colonization in atopic dermatitis patients resulted from the reduction of cathelicidin production in these patients. Recently, an in vivo study demonstrated that vitamin D could stimulate cathelicidin production. Oral supplements of vitamin D might be beneficial in atopic dermatitis. OBJECTIVE: To determine the effects of oral vitamin D supplements on clinical impact including Staphylococcus aureus skin colonization evaluation in atopic dermatitis patients. MATERIAL AND METHOD: Twenty-four atopic dermatitis patients were included in this double-blind, placebo-controlled study. They were randomly assigned into 2 groups for oral 2,000 IUs/day of vitamin D, supplement and placebo. The lesional swab culture for S. aureus was done at week 0, 2 and 4. Clinical outcomes were assessed by SCORAD score, mexameter for erythema index and konometer for conductance were done at week 0, 2 and 4. Serum vitamin D levels were also determined at week 0 and 4. RESULTS: Twenty patients completed the protocol. S. aureus skin colonization, SCORAD score and erythema index were significantly reduced from baseline to week 4for vitamin D treated group comparing with placebo (p = 0.022, 0.028 and 0.014, respectively). There was an inverse correlation between serum vitamin D levels with S. aureus skin colonization and SCORAD score (r = -1.0, p < 0.001). CONCLUSION: Oral vitamin D supplement could reduce skin colonization of S. aureus and demonstrated the clinical improvement of patients with atopic dermatitis. PMID- 26817208 TI - Effects of Phikud Navakot Extract on Myocardial Ischemia/Reperfusion Injury in Rats. AB - BACKGROUND: Phikud Navakot (PN) is a set of nine medicinal plants and the main ingredient of "Yahom Navakot", a traditional Thai herbal formula for treatment of cardiovascular symptoms. OBJECTIVE: To investigate the cardioprotective effects of PN on myocardial ischemia/reperfusion (IR) in male Sprague Dawley rats. MATERIAL AND METHOD: Rats were randomly divided into 7 groups: sham, IR, and IR orally pretreated with PN (10, 50, 100, 200, and 400 mg/kg B W)for 7 days. After treatment, IR induction was performed by left coronary artery (LCA) ligation for 30 min, followed by reperfusion for 24 h. At the end of the experiment, blood was collected for hematological and biochemical parameters, and hearts were immediately removed for histopathological examination and Western blot analysis. RESULTS: IR induction caused ST elevation in the electrocardiogram and an increase in serum troponin I (TnI), confirming myocardial damage. In addition, histopathological changes of ischemic myocardium showed inflammation, infiltration, and edema. Oral administration of PN (10, 50, 100, 200, and 400 mg/kg BW) for 7 days prior to IR simulation showed no change on serum TnI and histopathology ofcardiac tissues, when compared to IR group. However Western blot analysis showed that IR rats pretreated with PN (10 mg/kg BW) significantly increased (p < 0.05) pERK/ERK ratio, meanwhile pretreated with PN (50-200 mg/kg BW) up-regulated (p < 0.05) the protein expression of HO-1, when compared with IR group. CONCLUSION: The present study implied that 7-day pretreatment of PN failed to protect cardiac tissues against IR injury induced by LCA ligation. Investigation at molecular level found however that PN up-regulated the expression of protective proteins pERK/ERK ratio and HO-1 in cardiac tissues, suggesting molecular mechanism of PN in cardioprotection against IR injury. PMID- 26817209 TI - Chronic Effect of Thunbergia laurifolia Extract and Cocaine in Rats Using Behavior Model of Addiction. AB - BACKGROUND: Thunbergia laurifolia Linn. (TL) is a herbal medicine which has been used as a component of a mixture ofcrude extracts to treat drug addicted patients. TL extract was reported to increase dopamine levels significantly in the rat brain both in vitro and in vivo studies similar to that seen with cocaine and TL stimulated in the same brain area that amphetamine stimulated. OBJECTIVE: The study aims to investigate whether long term treatment with TL can cause addiction or not by comparing with known addicted drug, cocaine, using the conditioned place preference test. MATERIAL AND METHOD: Chronic oral administration (30 days) of crude water extract of TL (1 and 10 g/kg, orally) and cocaine (1 mg/kg, orally) were performed to determine the alteration of addiction behavior using a conditioned place preference (CPP) test. RESULTS: Rats received chronic treatment ofcocaine became addicted. While, both doses of TL (1 and 10 g/kg, orally) did not cause significantly in the time spent in both compartment between pre- and post-drug treatment. CONCLUSION: When treated long-term and tested with CPP test of addiction, rats received chronic treatment ofcocaine became addicted. On the other hand, both doses ofcrude water extract of TL (1 and 10 g/kg, orally) did not cause significant changed in the time spent in both compartment between pre- and post-drug treatment indicating that TL did not cause addiction. PMID- 26817210 TI - Alpha-Mangostin Partially Preserves Expression of Ammonia-Metabolizing Enzymes in Thioacetamide-Induced Fibrotic and Cirrhotic Rats. AB - BACKGROUND: Ammonia metabolizing enzymes, carbamyol phosphate synthetase (CPS) and glutamine synthetase (GS), are expressed in the periportal and pericentral hepatocytes, respectively. CPS and GS function complementary to ensure complete ammonia detoxification. Immunohistochemical analysis confirmed the decline of both CPS and GS in cirrhotic rat liver induced by thioacetamide (TAA). Alpha mangostin (AM), a major derivative of xanthone from mangosteen, has been reported to possess a wide range of pharmacological properties. OBJECTIVE: To examine the preventive effects of AM on CPS and GS expression in fibrotic and cirrhotic rats induced by TAA over sixteen weeks. MATERIAL AND METHOD: Twenty-four male Wistar rats were divided into 4 groups of 6 animals each. Group 1 was for control. Group 2 wasfor pure TAA treatment. Group 3 was for pure AM administration. Group 4, prevention group, was concurrently treated with TAA and AM. Immunohistochemical technique was employed in order to elucidate the expression of CPS and GS in each animal group. RESULTS: Immunohistochemical staining for CPS and GS showed an increasing decline from week eight to sixteen under pure-TAA condition. Fibrous bridgings, nodule formations, and regenerative nodules were detected. Pure-AM condition yielded strongly CPS and GS-stained hepatocytes in afashion similar to the control. Results from the prevention group showed a decreasing decline of CPS and GS immuno-reactivity from week eight to sixteen as compared to pure-TAA condition. Fewer fibrous portal-caval bridgings were observed at week eight and CPS-positive hepatocytes were found in continuous rings. CONCLUSION: Alpha mangostin could partially preserve the normal expression of ammonia-metabolizing enzymes under TAA-induced fibrotic and cirrhotic conditions. PMID- 26817211 TI - Comparisons of Latching on between Newborns Fed with Feeding Tubes and Cup Feedings. AB - BACKGROUND: Feeding tubes and cup feedings were used as alternative feedings. There is scant data regarding the facilitation of latching on by newborns with the use of these alternative supporting techniques. OBJECTIVE: The comparison of the latching on of newborns when fed with the additional support of feeding tubes or cup feedings. MATERIAL AND METHOD: The subjects were 120 normal, postpartum women, who delivered without complications at the HRH Princess Maha Chakri Sririndhorn Medical Center in the Nakhon Nayok Province between October 2012 and September 2013. No breast milk was expressed by the mothers at day 2, postpartum. They were divided into two groups by simple randomization. In the first group, the newborns were fed with a feeding tube in support of breastfeeding. In the second group, the newborns were fed by cup feedings. Latch scores were assessed at the end of postpartum day 3. Demographic data and latch scores were collected and analyzed by Chi-square, t-test and Mann-Whitney U test. RESULTS: No differences in the demographic data of mothers and newborns between the two groups were found. Latch scores for the feeding tube group were significantly higher than the latch scores in the cup feeding group (p < 0.05). CONCLUSION: Latching of newborn after feeding tube method is better than latching of newborn after cup feeding. PMID- 26817212 TI - Epidemiology of Candida Infections in HRH Princess Maha Chakri Sirindhorn Medical Center, Srinakharinwirot University. AB - OBJECTIVE: To identify the epidemiology of candida isolations in HRH Princess Maha Chakri Sirindhorn Medical Center and the sensitivity of all candida species to fluconazole. MATERIAL AND METHOD: Two hundred of Candida albicans and other Candida species from clinical specimens were collected from microbiological department between January 2010 and April 2012. All Candida were identified by standard methods and the sensitivity of fluconazole was tested by using fluconazole E test test. RESULTS: There were 8 species of Candida in this study including: C. albicans (n = 94), C. tropicalis (n = 66), C. glabrata (n = 11), C. guilliermondii (n = 10), C. parapsilosis (n = 9), C. zeylanoides (n = 4), C. keyfr (C. pseudotropicalis) (n = 2), C. lusitaniae (n = 1), Candida species (n = 3). The percentage of non-albicans Candida spp. was slightly higher than C. albicans (53% vs. 47%). C. tropicalis was identified as the highest percentage of all non-albicans Candida spp. Fluconazole resistant strains were detected among C. albicans (35.71%), C. tropicalis (13.85%), C. guilliermondii (20.0%), and C. zeylanoides (50.0%). The common spp. with highest percentage of resistant strain was C. albicans. CONCLUSION: Fluconazole could be used as thefirst-line antifungal for candidiasis at HRH Princess Maha Chakri Sirindhorn Medical Center. Empirical treatment with amphotericin B and steppingdown tofluconazole when sensitivity suggested might be the recommendation for severe cases in our setting. PMID- 26817213 TI - Sleep Behaviors and Sleep Problems in School-Aged Children in Thailand. AB - BACKGROUND: Sleep problems can have a significant effect on children behaviors, emotional and cognitive developments. However, limited information is available regarding the sleep behaviors and sleep problems of school-aged children in Thailand. The purposes of this study were to examine the prevalence of sleep problems and to describe sleep/wake pattern of Thai children. MATERIAL AND METHOD: The school-based, cross-sectional study was conducted in 5 primary public schools selected from Bangkok and three regions of Thailand. The samples were selected from the first and fourth grades of each school. The Children's Sleep Habits Questionnaire (CSHQ) was used to evaluate sleep behaviors and sleep problems. RESULTS: Grade 1 children went to bed earlier and had longer weekday sleep duration comparing with grade 4 children. Sleep duration was significantly shorter in children living in Bangkok, comparing with those living in rural areas. Mean total CSHQ score was significant higher in grade 1 children, when comparing with grade 4 children (51.30 vs. 50.18; p = 0.026). Grade 1 children scored significantly higher on bedtime resistance (10.96 vs. 10.39; p = 0.004) and sleep anxiety subscale (6.68 vs. 6.41; p = 0.022), while grade 4 children scored significantly higher on sleep-onset delay subscale (1.41 vs. 1.23; p < 0.001). Prevalence of sleep problems was highest in the category of "falling asleep while riding in car or bus" (69.5%), followed by "awakening by others in the morning" (68.5%). CONCLUSION: Sleep problems were common in Thai school-aged children. The most common sleep problems were in the domains of daytime sleepiness and bedtime resistance and anxiety. PMID- 26817214 TI - Detection of Pathogenic Leptospires by Loop-Mediated Isothermal Amplification Targeting LipL32 Gene. AB - BACKGROUND: Leptospirosis is a worldwide re-emerging infectious disease caused by pathogenic leptospires including Leptospira interrogans. OBJECTIVE: In the present study, a loop-mediated isothermal amplification (LAMP) was developed to detect L. interrogans using lipL32 as a gene target. MATERIAL AND METHOD: Four specific primers were designed based on the conserved region of lipL32 gene of various serovars ofpathogenic leptospires. LAMP reaction was performed at 65 degrees C for 1 hour The LAMP products were detected by agarose gel electrophoresis andfluorescence dye. RESULTS: The lipL32 LAMP assay showed highly specificity to the reference stains of L. interrogans serovar Autumnalis, Bataviae, Javanica, Pyrogenes, Icterohaemorrhagiae, and Saigon. No product was produced from non-pathogenic leptospire (L. biflexa), human, or Escherichia coli. The lower limit of detection analyzed by agarose gel electrophoresis andfluorescence dye visualization was 0.02 pg/ul which equivalent to 4 genomic equivalents/reaction. Moreover the clinical strain of leptospires including pathogenic and intermediate group of L. interrogans were detected by lipL32 LAMP CONCLUSION: The developed lipL32 LAMP is high specificity and sensitivity that can be applied to detect pathogenic leptospires in clinical samples. PMID- 26817215 TI - Apolipoprotein E receptor 2 Gene Polymorphisms Associated with Dyslipidemia among Thai Population. AB - BACKGROUND: Dyslipidemia is an abnormal amount of lipids and/or lipoproteins in the blood. It is a major risk factor of coronary heart disease and atherosclerosis. OBJECTIVE: This study investigated two single nucleotide polymorphisms (SNPs) in the apolipoprotein E receptor 2 (ApoER2) gene in association with risk of dyslipidemia in the Thai patients. MATERIAL AND METHOD: Four hundred blood samples including dyslipidemia patient (200) and unrelated normal control (200) were included in this study. Serum lipids were examined. DNAs were extracted and genotyped by using polymerase chain reaction (PCR) followed by high-resolution melting (HRM) analysis. The differences in genotype distribution between patient and normal control were assessed by Chi-square test of the SPSS software version 11.5. RESULTS: The data analysis revealed that two SNPs (rs3737984 and rs2297660) in ApoER2 gene had significant association with dyslipidemia. The rs3 737984 showed significant association at p-value = 0.001, in which A alleles informed the decreased risk of dyslipidemia [odds ratio and 95% CI of A allele, 0.42 (0.28-0.65)]. In contrast, the rs2297660 exhibited strongest association with an increase risk ofdyslipidemia [p-value = 0.001, odds ratio and 95% CI for theA allele was 2.38 (1.49-3.80)]. CONCLUSION: The rs2297660 may be used as biomarker for the risk of dyslipidemia in Thai ethnic. PMID- 26817216 TI - Investigation of Therapeutic Effects of alpha-Mangostin on Thioacetamide-Induced Cirrhosis in Rats. AB - OBJECTIVE: To determine the effects of alpha-mangostin on thioacetamide (TAA) induced liver cirrhosis in rats. MATERIAL AND METHOD: Male Wistar rats were divided into 3 groups and treated with intraperitoneal injections of TAA (200 mg/kg) 3 times per week for per week for 8, 12 and 16 weeks, respectively. One subgroup was left untreated whereas the other two were treated either with 100 mg/kg alpha-mangostin or vehicle alone (80% DMSO, 20% water), which were administered intraperitoneally 3 times per weekfor a total of4 weeks. The incidence offibrotic nodules on the liver and the serum levels of the liver enzymes aspartate transaminase (AST) and alanine transaminase (ALT) were measured. Moreover the liver cirrhosis-related genes expression and p53 protein level in liver were analyzed by quantitative reverse transcription PCR and Western blot analysis, respectively. RESULTS: Fibrotic nodules on the liver were formed upon treatment with TAA for 12 or 16 weeks. The nodules were then reduced by treatment with alpha-mangostin as compared to treatment with the vehicle DMSO. Moreover, the serum levels of the liver enzymes AST and ALT after treatment with alpha-mangostin decreased as compared to DMSO alone. The liver cirrhosis-related genes expression showed no significant differences, whereas the p53 protein level in liver showed that alpha-mangostin reduced risk of liver fibrosis through the decrease in p53 expression as compared to the TAA_DMSO treatment. CONCLUSION: The results suggest that alpha-mangostin has a beneficial therapeutic effect in the TAA liver cirrhosis model. Further investigations on mechanisms of alpha mangostin as therapeutic agent should be determined. PMID- 26817217 TI - The 2-Year Outcomes Comparison between Ischemic Stroke Patients with Intracranial Arterial Stenosis without Significant Extracranial Carotid Stenosis and Patients with Extracranial Carotid Stenosis. AB - OBJECTIVE: The risk of recurrent ischemic stroke and acute coronary syndrome increased in the large artery atherosclerotic subtype. The purpose of this study was to compare 2-year outcomes between the ischemic stroke patients with intracranial arterial stenosis without significant extracranial carotid stenosis and the patients with extracranial carotid stenosis. MATERIAL AND METHOD: This study prospectively compared 123 ischemic stroke patients: 71 patients with intracranial arterial stenosis without significant extracranial carotid stenosis and 52 patients with extracranial carotid stenosis. Neurologic and radiologic investigations were performed at the beginning of the study. All of them were treated as regular outpatients of the neurology unit with a mean follow-up of 24 months. Recurrent stroke, myocardial infarction, and death were recorded. RESULTS: Fifteen patients of the extracranial carotid stenosis group and eighteen patients ofthe intracranial arterial stenosis without significant extracranial carotid stenosis group developed recurrent stroke during follow-up (p = 0.40). Acute coronary syndrome occurred in eight patients of the extracranial carotid stenosis group and only one of the intracranial arterial stenosis without significant extracranial carotidstenosis group (p = 0.004). Causes of death were end stage cancers, stroke and related conditions, and acute coronary syndrome. The multivariate analysis showed that symptomatic extracranial carotid stenosis is an important risk factor of the acute coronary syndrome (p = 0.03, OR = 10.81, 95% CI 1.23-94.77). CONCLUSION: There was no significant difference of recurrent ischemic stroke and recurrent stroke between patients with intracranial arterial stenosis without extracranial carotid stenosis and patients with extracranial carotid stenosis. On the other hand, patients with extracranial carotid stenosis had more incidences of acute coronary syndrome significantly than patients with intracranial arterial stenosis. PMID- 26817218 TI - Echocardiographic and Clinical Characteristics Cross-Sectional Study in Association with Thai Peritoneal Dialysis Patients: Data from a Single Center Study. AB - BACKGROUND: The dialysis patients have a lot of changes in cardiac structure and function detected by echocardiography and they have been recognized as key outcome predictors. However, the available data regarding echocardiographic alterations in Thai Continuous Ambulatory Peritoneal Dialysis (CAPD) patients is limited. This study aimed to determine the correlation between baseline clinical and echocardiographic characteristics of Thai CAPD patients. MATERIAL AND METHOD: This study was a single center and cross-sectional observational study, which enrolled all CAPD outpatients (104 patients), treated at Srinakharinwirot Medical University between 1 September 2012 and 31 June, 2014. Their demographic and echocardiographic data were collected one time and the latest laboratory data to the patient's echocardiographic study date were analyzed. RESULTS: One hundred and four patients (50 men and 54 women) whose mean age was 59.4 +/- 12.7 years and median duration of CAPD was 12 months were recruited. An extremely high prevalence of elevated left ventricular mass index (LVMI), 82.7% was found which mean LVMI was higher in male than female (166.2 +/- 55.6 vs. 131 +/- 47.6 g/m2). All patients had diastolic dysfunction and most ofthem had diastolic dysfunction grade I. The studyfactors of male gender, history of hypertension, high serum phosphate, low hemoglobin level, corrected QT interval, and duration of CAPD longer than 24 months can predict the variation of LVMI. Interestingly, the study found that a duration of CAPD of longer than 42 months might reduce right ventricular systolic pressure. CONCLUSION: This study revealed a higher prevalence of left ventricular hypertrophy (LVH) in Thai CAPD patients when compared with previous studies and anemia still be an important independentfactor for developing LVH. Longer period of CAPD may regress LVH and lower RVSP that should be proven by longer well-designed prospective studies. PMID- 26817219 TI - Antimicrobial Properties of a Potential Probiotic Lactobacillus from Thai Newborn Feces. AB - BACKGROUND: Probiotics are increasingly used to treat infectious diarrhea and antibiotic-associated diarrhea. Many probiotic bacteria are classified in general such as Lactobacillus and are able to colonize the gastrointestinal tracts of infants. OBJECTIVE: This study was performed to detect antimicrobial substances and activity in 200 Lactobacillus isolates obtained from healthy Thai newborn feces. MATERIAL AND METHOD: Reuterin production was detected by the spot overlay technique and colorimetric assay. Antimicrobial activity was tested by using a well diffusion, agar method. RESULTS: Lactobacillus strain MSMC64-1 produced reuterin and demonstrated potent antimicrobial activity against seven pathogenic indicator strains with very strong inhibitory activities against Salmonella typhi DMST 5784 and methicillin resistant Staphylococcus aureus (MRSA) DMST 20651. There was strong inhibitory activity against methicillin resistant Staphylococcus aureus (MRSA) DMST20654, Vibrio parahaemolyticus DMST 5665 and Shigella dysenteriae DMST 15111. There was moderate to weak inhibitory activities against Vibrio cholerae DMST 2873 and Helicobacter pylori (H40). The Lactobacillus strain MSMC 64-1 showed resistance to acidic pH (pH 2, 3, 4) and tolerance to 1%, 2%, 3%, and 4% bile concentrations. Sequencing of the 16S ribosomal DNA identified the candidate's strain as Lactobacillus reuteri with 98% sequence homology. CONCLUSION: The active isolate could potentially be used as a probiotic to prevent and treat enteric infections. PMID- 26817220 TI - Development of Clock Genes Expression in Rat Hippocampus. AB - BACKGROUND: The circadian rhythms in the suprachiasmatic nucleus (SCN), a central clock, are generated by autoregulatory network composed ofclock genes that encode transcriptionalfactors. There is a gradual development ofclock gene expression in the SCN during ontogenesis. Moreover clock genes are expressed in the adult hippocampus with circadian fashion. OBJECTIVE: It is of interest to examine daily profiles ofthe clock gene mRNA and protein expressions in rat hippocampus during development. MATERIAL AND METHOD: Daily profiles ofthree clock genes (Per1, Per2, and Bmal1) mRNA, and their protein expressions were analyzed in the rat hippocampus ofpups at postnatal (P) day 4 and 8 (P4 and P8), pre-weaning stage (P16), early pubertal stage (P32), and adult (P60) by real-time PCR and immunohistochemistry. RESULTS: The entire studied clock gene mRNAs and proteins did not exhibit circadian rhythm in early postnatal P4-P16. Rhythmic expression of Per1 and Per2 mRNA started at P32, whereas Bmal1 began at adult. However, their proteins showed circadian expression together at adult. CONCLUSION: The present study suggests that rat hippocampal molecular clock works gradually develop after birth and slower than that in the central clock SCN. It was possible that ontogenetic development of clock gene in hippocampus was waitingfor central clocksynchronization. PMID- 26817221 TI - Effects of Laughing Training on Stress Levels in Thai Private Office Workers. AB - BACKGROUND: Laughing is a kind of well known alternative medicine used to treat stressful persons or depressive patients to relax. The laughing program used in this study was initially designed by Thai psychiatrists. It consists of deep diaphragmatic breathing exercises, voice expression, facial expression exercises and aerobic exercises, which are expected to promote good health. OBJECTIVE: To evaluate the effects of the laughing training on stress levels in Thai private office workers. MATERIAL AND METHOD: Thirty-eight subjects whose age 25-60 years were recruited to enroll in this program. They were randomly divided into two groups: 20 people for the experimental group and 18 persons for the control group. The experimental subjects participated in laughing program for 3 days/week, 60 minutes/day for 8 consecutive weeks. The program took place from June to July 2013. The level of stress was assessed using the Suanprung stress test-60 (SPST-60). The data were analyzed by descriptive statistics, t-test dependent and t-test independent with p < 0.05 considered significant. RESULTS: After they joined the laughing program, no significant difference was found in the mean scores of the level of stress between the control and experimental groups. However, the sensitivities to the arousal events in the experimental group had a tendency to decrease. CONCLUSION: Laughing training may be used as a tool to promote better health. There was no significant difference in the stress levels after the program was ended except a decrement tendency in the sensitivities to the arousal events. For further study, duration and intensity of the course may be adjusted for a more effective training program. PMID- 26817222 TI - Self-Medication for Dermatologic Diseases among Children Treated at the HRH Princess Maha Chakri Sirindhorn Medical Center. AB - BACKGROUND: Skin diseases are one of the common problems in Pediatrics Outpatient Department. Because self-medication is practiced, it raises concerns of incorrect self-diagnosis, adverse drug reactions, and the cost of self-treatment. The aim of this study was to investigate the prevalence and the features of self medicating for skin diseases among children who were observed at the dermatology clinic. MATERIAL AND METHOD: This prospective study was conducted in the Pediatric Outpatient Department. All patients seen on a first visit for skin problems were recruited, interviewed, and examined. RESULTS: Four hundred thirty seven patients were recruited in the study and the mean age was 4.6 years of age. Eczema was the most common diagnosis (43.7%), followed by fungal skin infections (7.1%), insect bites and infestations (6.9%), and bacterial skin infections (6.2%). Of all the patients, 204 (46.7%) had used self-medication. The most common reasons for self-medicating were convenience (82.3%), a friend and/or relative's recommendation (15.2%), and avoiding the cost of doctors' visits (2.0%). The most frequently encountered categories of medicines were topical corticosteroids (25.4%), antifungal agents (13.4%), antibacterial agents (8.2%), and others. Most products were obtained from pharmacies (66.2%). The average cost for self-medications was 204.7 Thai baht. Products applied by the topical route were the most common medications used (81.3%) and most patients had reported dissatisfaction with the results (95.1%). Adverse reactions resulting from self medications were found to be at a rate of 17.1%. There were no significant relationships (p > 0.05) between the practice of self-medication and the potential factors. CONCLUSION: Self-medication use is most prevalent. Most patients had reported dissatisfaction from the use of self-medications. Adverse reactions resulting from self-medication were also found. PMID- 26817223 TI - Comparison of Droplet Digital PCR and Real Time PCR Method for HBV DNA Quantification. AB - BACKGROUND: HBV infection causes a potential serious public health problem. The ability to detect HBV DNA concentration is an important issue that had been continuously improved. When using quantitative polymerase chain reaction (qPCR), several factors are of concern, for example, sources of material, standard curve calibration, and PCR efficiency. Digital PCR (dPCR) is an alternative PCR-based technique for absolute quantification using Poisson's statistics without requiring a standard curve. OBJECTIVE: Compare the data set of HBV DNA generated between dPCR and qPCR methods. MATERIAL AND METHODS: Fifty-four samples were quantified by Abbot's real time PCR and with 2-6 log10 HBV DNA were selected for comparison with dPCR. RESULTS: Of these 54 samples, there were two outlier samples defined as negative by dPCR, whereas 52 samples were positive by both of these assays. The difference between two assays was less than 0.25 log IU/mL in 24/52 samples (46%) of paired samples; less than 0.5 log IU/mL in 46/52 samples (88%) and less than 1 log in 50/52 samples (96%). The correlation coefficient (r) was 0.788 (p-value < 0.0001). Comparison with qPCR method, data generated by dPCR tend to be an overestimation in the sample with the low level ofHBVDNA concentration and underestimated in the sample with high viral load. The variation of DNA by dPCR measurement might be due to the pre-amplification procedure and PCR template. CONCLUSION: Measurement of HBV DNA by using dPCR, the results ofthe HBV DNA copy number tended to be deviated by over- or under estimated when comparison to real time PCR method. In addition, a large quantity of DNA was used when compared to qPCR. However, the optimum processes of this assay have to be further investigated. PMID- 26817224 TI - Antiproliferation and Apoptosis Induction in Colorectal Cancer Cells by Goniothalamin. AB - OBJECTIVE: To investigate the effect of goniothalamin on antiproliferation and apoptosis induction in three types of colorectal cancer cells. BACKGROUND: Colorectal cancer is the third of the twentieth most commonly diagnosed cancer. Different types of colorectal cancer cells differ in genotype and characteristics leading to different responses to anticancer drugs. Therefore, finding new anticancer compound for the colorectal cancer cells is necessary. MATERIAL AND METHOD: Antiproliferative response of goniothalamin on three colorectal cancer cell lines including Colo 205, SW480, and LoVo were determined by MTT assay. The antiproliferative response at different time and dose was also observed. Apoptosis induction by goniothalamin was observed in all three cell-lines via morphological changes and nuclear condensation by Hoechst33342 staining. RESULTS: Goniothalamin showed different antiproliferative response on Colo 205, SW480, and Lo Vo cells at the IC50 value is 9.86 +/- 0.38 uM, 22.00 +/- 4.40 uM, and 65.25 +/- 1.85 uM respectively. In addition, the antiproliferative response of goniothalamin was a time- and dose-dependent manner Apoptosis morphological changes and nuclear condensation were clearly observed in Colo 205, SW480 and LoVo cells treated with 10 uM, 25 uM, and 50 uM goniothalamin, respectively. CONCLUSION: Goniothalamin showed antiproliferation and apoptosis induction in colorectal cancer cells with different sensitivity depending on cell type. Investigation of mechanisms underlying apoptosis and its potential use for colorectal cancer treatment should be further studied. PMID- 26817225 TI - Effect of Inhaling Bergamot Oil on Depression-Related Behaviors in Chronic Stressed Rats. AB - BACKGROUND: Bergamot essential oil (BEO) possesses sedation and anxiolytic properties similar to diazepam. After long period of exposure to stressors, including restrained stress, depressive-like behavior can be produced. BEO has been suggested to reduce depression. However, there is no scientific evidence supporting this property. OBJECTIVE: To investigate the effect of BEO in chronic stressed rats on: 1) behavior related depressive disorder, 2) hypothalamic pituitary adrenal (HPA) axis response, and iii) brain-derived neurotrophic factor (BDNF) protein levels in hippocampus. MATERIAL AND METHOD: Male Wistar rats, weighing 200 to 250 g, were induced chronic restrained stress 15 minutes dailyfor two weeks. For the next two weeks, these rats were divided intofour groups, control-i.p., fluoxetine-i.p., control-inhale, and BEO-inhale. Fluoxetine (10 mg/kg i.p.) or saline was intraperitoneally administered daily while 2.5% BEO or saline was inhaled daily. At the end of the treatment, rats were assessed for depressive-like behavior using the forced swimming test (FST). After the behavioral test, the animals were immediately decapitated and trunk blood samples were collected for the measurement ofcorticosterone and adrenocorticotropic hormone (ACTH) levels and hippocampus was dissected and stored in afreezer at -80 degrees C until assay for BDNF protein. RESULTS: BEO andfluoxetine significantly decreased the immobility time in the FST (p < 0.05). Fluoxetine tended to decrease serum corticosterone and significantly (p < 0.05) decreased serum ACTH while BEO had no effect on these two stress hormones. For BDNF protein determination, neither BEO norfluoxetine had any effect on BDNF protein levels in hippocampus compared to their controls. CONCLUSION: The inhalation ofBEO decrease behavior related depressive disorder similar tofluoxetine but has no effect on HPA axis response and BDNF protein levels in chronic restrained stress. PMID- 26817226 TI - Pelvic Retroperitoneal Cellular Leiomyoma: A Case Report. AB - Leiomyomas are common benign gynecological tumors and usually arise in the uterus. The retroperitoneal cellular leiomyoma, one of the unusual manifestations, is a rare tumor. Diagnosis and treatment are challenges. We report a case of 65-year-old women presented with an asymptomatic mass beneath the right posterior vaginal mucosa. CT imaging revealed heterogeneous mass 6 cm in the pelvic cavity abutted lower segment of uterus, cervix, and vagina. The provisional diagnosis was subserosal cervical leiomyoma. She underwent exploratory laparotomy. Intra-operative, a normal size uterus was found separately from retroperitoneal pelvic mass at the level of internal os. Histological report confirmed cellular leiomyoma later Total hysterectomy, bilateral salpingoophorectomy and completely excision of tumor were achieved with good outcome. Our patient represents the rare case of retroperitoneal cellular leiomyoma, which is hardly identified from internal examination and preoperative imaging. Surgical removal is essential for pathological diagnosis and treatment. PMID- 26817227 TI - A Case of Hemichorea Caused by Cerebral Cavernous Angioma. AB - Chorea is a type of hyperkinetic movement, referring to involuntary, irregular, aimless, nonrhythmic, abrupt, rapid, unsustained movements. The term hemichorea refers to chorea ofone side of the body. A 39-year-old woman presented with a three-week history of abrupt, involuntary movements of her right hand and right foot, which was compatible with hemichorea ofthe right side. MRI brain showed a 1.7 x 1.5 x 1.3 cm lesion in the posterior limb of the left internal capsule and the lateral part of the left thalamoganglionic region, which was seen as mixed iso- and hyperintense in T1W images, and heterogeneous and hyperintense in T2W/FLAIR images. T2 gradient sequences showed a peripheral rim of decreased signal intensity, which is the hemosiderin ring, and no significant brain edema. Partial contrast enhancement of the lesion after contrast media injection suggested cavernous angioma. After medical treatment with haloperidol 2.5 milligrams per day, her symptom gradually improved within 2 months. PMID- 26817228 TI - Human Erysipelothrix rhusiopathiae Infection: Unsolved Issues and Possible Solutions. AB - Erysipelothrix rhusiopathiae infection in humans may not be as rare as previously thought. In most cases, the disease is acquired from animals through work-related exposure. Human infection has been reported since the early 1900's up to the present. Unsolved issues associated with this organism include inadequate disease control in animals, difficulty in identification and isolation of the bacteria, diagnostic delay due to unawareness of this uncommon disease or unfamiliarity with the increasingly diverse clinical manifestations, and inappropriate antibiotic use due to misdiagnosis, as well as drug resistance. In this review, we attempt to address the unsolved issues related to human Erysipelothrix infection and suggest possible solutions. PMID- 26817229 TI - Iatrogenic Esophageal Perforation. AB - Iatrogenic esophageal perforation is the most common cause of esophageal perforation associated with high mortality rate of 19%. Acute sudden onset of pain after endoscopic intervention is the most common presenting symptom. Water soluble contrast study, CT scan, and endoscopy provide a high sensitivity for diagnosis of iatrogenic perforation. Non-operative management is safe and effective treatment for early perforation (< 24 hours) without clinical signs of sepsis. However, surgical management such as primary repair esophageal exclusion and diversion, and esophagectomy is warranted in the patients who did not meet the criteria for non-operative management. Endoscopic management (clip, esophageal stent) is an alternative treatment option with 80 to 90% of esophageal healing rate. Early recognition of suspicious symptoms within 24 hours, the use of the appropriate investigation, selection of the optimal treatment options, and multidisciplinary critical care are the best way to improve outcomes. PMID- 26817230 TI - Fourth Academic Symposium of the College of Medicine and Public Health, Ubon Ratchathani University Thailand's Healthcare System Strategy: The Road Ahead. PMID- 26817231 TI - Relapsed Melioidosis Model in C57BL/6 Mice. AB - BACKGROUND: Burkholderia pseudomallei are the causative agents of melioidosis, a disease that has a high relapse rate in endemic areas. The mechanism of relapse is unclear OBJECTIVE: This study aimed to establish relapsed melioidosis in C57BL/6 mice by induction with B. pseudomallei. MATERIAL AND METHOD: Low doses of B. pseudomallei H777 and its biofilm defective mutant (M10) were intra-gastric fed to C57BL/6 mice. All the infected mice had suppressed immune status by intra peritoneal injection of hydrocortisone at 2.5 mg per mouse at day 60 post infection. Inflammatory response to the infection was investigated by histo pathological studies and monitoring bacterial counts in the blood and organs. RESULTS: All the infected mice were found to have a high infiltration of mononuclear cells at day 60 post-infection. The results showed high bacterial counts in the blood in both strains post-suppressed immune status after two days. The biofilm mutant and wild type strains produced relapse in C57BL/6 mice but the latter was responsible for significantly more severe inflammation than the biofilm mutant. CONCLUSION: Low immune status may cause relapsed melioidosis in hosts with chronic inflammation. PMID- 26817232 TI - Antibacterial Activity of Excretions-Secretions from Chrysomya megacephala Against Escherichia coli. AB - BACKGROUND: The blowfly, Chrysomya megacephala, is distributed worldwide. Previous studies found maggot excretions-secretions from other blowfly species inhibited pro-inflammatory response and antimicrobial activity. OBJECTIVE: This study aimed to test the bactericidal activity of excretions-secretions from C. megacephala larvae. MATERIAL AND METHOD: A total of 1,500 3-day-old larvae were used to collect excretions-secretions (ES) modified by the Barnes method. The bactericidal activity ofthe excretions-secretions was test by Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli using suitable liquid culture assay. Scanning electron microscope (SEM) was used to investigate the morphological change ofthe bacteria. RESULTS: E. coli were significantly inhibited by excretions-secretions from C. megacephala larvae. P. aeruginosa and S. aureus were not found to inhibit growth. CONCLUSION: The excretions-secretions from C. megacephala larvae may have a medical property for the inhibition of bacterial growth. PMID- 26817233 TI - Prevalence of bla(PenA) and bla(OXA) in Burkholderia pseudomallei Isolated from Patients at Sappasitthiprasong Hospital and Their Susceptibility to Ceftazidime and Carbapenems. AB - BACKGROUND: Burkholderia pseudomallei is a causative agent of melioidosis. Ceftazidime is the preferred drug of choice for treatment. However, the motility rate is high in endemic areas. OBJECTIVE: This study aimed to determine the susceptibility tofour different antimicrobial agents and to detect the beta lactamase genes in B. pseudomallei isolates from patients admitted to Sappasitthiprasong Hospital. MATERIAL AND METHOD: 85 B. pseudomallei isolates from patients admitted to Sappasitthiprasong Hospital between November 2010 and May 2011 were determined for antimicrobial susceptibility by standard disk diffusion and minimum inhibitory concentration (MIC). Real-time polymerase chain reaction (PCR) was used for the detection of bla(penA) and bla(OXA) in beta lactamase genes. RESULTS: Almost all of the clinical isolates ofB. pseudomallei were susceptible to ceftazidime and imipenem. Cefatzidime MIC was <= 1-16 MUg/ml and imipenem MIC was <= 1-4 MUg/ml. The real-time PCR revealed that more than 90% of B. pseudomallei isolates carried bla(PenA) and bla(OXA). CONCLUSION: Although the clinical isolates of B. pseudomallei were susceptible to ceftazidime and imipenem, this study showed B. pseudomallei had a gene that produced beta lactamase enzyme and may be poorly effective in the use of beta-lactam drugs. PMID- 26817234 TI - Detection of Leptospira in Rats Trapped from Households in Phraroj Village, Muang Sam Sip District, Ubon Ratchathani Province Using Polymerase Chain Reaction Technique. AB - BACKGROUND: Leptospirosis, a zoonotic disease caused by Leptospira, has been a health problem in Thailand for several years. Rats are a major reservoir host for Leptospira, and the people who are usually in contact with environments contaminated with rats' urine are at risk of infection. The prevalence rate of Leptospira infection in rats may result in the spread of leptospirosis in humans. OBJECTIVE: This study aimed to determine the prevalence rate ofLeptospira infection in a total of 28 rats and develop a spatial database for leptospirosis surveillance in Phraroj village in Muang Sam Sip District, Ubon Ratchathani Province. MATERIAL AND METHOD: The positions of the households and the rat trapping area were tagged by using of a Global Positioning System (GPS). DNA samples were isolated fromn rats' kidneys. The polymerase chain reaction (PCR) technique was used for the detection of 16s rRNA and LipL32 genes specific to genus and pathogenic Leptospira respectively. All of the data were used to develop a geo-data base by the connection of spatial data and attributed data to be used for query and retrieval. RESULTS: A map of the positions of the households and the rat-trapping area in Phraroj village was created. No rats were found to be infected in the Leptospira survey. CONCLUSION: There was no trapped rat infected with Leptospira in Phraroj village. This result may involve unreported leptospirosis in patients in this village. The Leptospira survey in rats and the geo-database will be used as a primary resource to support and make decisions about surveillance, prevention, and control of leptospirosis. PMID- 26817235 TI - Andrographolide Ameliorates Beta-Naphthoflavone-Induced CYP1A Enzyme Activity and Lipid Peroxidation in Hamsters with Acute Opisthorchiasis. AB - BACKGROUND: Opisthorchis viverrini (OV) infection generates oxidative stress/free radicals and is considered as a primary cause ofcholangiocarcinoma since it primarily triggers sclerosing cholangitis. OBJECTIVE: In this study, the impacts of andrographolide on acute opisthorchaisis in beta-naphthoflavone (BNF)-exposed hamsters were investigated. MATERIAL AND METHOD: Ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) activities and Thiobarbituric acid reaction substances (TBARS) assay of andrographolide in acute opisthorchiasis in the BNF-exposed hamsters were assessed. RESULTS: The results showed that andrographolide ameliorated the hepatic CYP1A1 and CYP1A2 activities by decreases of the specific enzymatic reactions of EROD and MROD, respectively, in the BNF-exposed hamsters. Moreover, andrographolide lowered the formation of malondialdehyde in the livers and brains of the hamsters. CONCLUSION: These observations revealed the promising chemo-protective and antioxidant activities of andrographolide via suppression of the specific EROD and MROD reactions and lipid peroxidation against acute opisthorchiasis in the BNF-exposed hamsters. PMID- 26817237 TI - Association between Alcohol Consumption and Pre-Diabetes among 383,442 Thai Population Aged 15 Years and Older in Ubon Ratchathani: Analytical Cross Sectional Study. AB - BACKGROUND: Alcohol consumption has been reported to be associated with the risk of diabetes. However, few studies have examined alcohol consumption as a risk factor for pre-diabetes in Asian populations. MATERIAL AND METHOD: This study is an analytical cross-sectional study aimed at determining the relationship between alcoholic consumption and pre-diabetes. This study used data on 383,442 men and women participating in the Health Checks Ubon Ratchathani (HCUR) project in 2007. Pre-diabetes was defined as a fasting blood glucose of > 100-125 mg%. Data on alcohol consumption was questioned and categorized into six groups: never, occasionally, 1-2 times/month, 1-2 times/week, 3-4 times/week and every day. Multivariable logistic regression was performed to estimate the association between self-reported alcohol consumption and pre-diabetes. RESULTS: The prevalence of pre-diabetes was 10.5% (11.2% and 9.7% in men and women, respectively). After adjusting for other risk factors, alcohol consumption was independently associated with pre-diabetes, with dose response relationship (adjusted odds ratio (OR(adj) of 1.80, 95% CI 1.53-2.11, p < 0.001 and 1.47, 95% CI 1.28-1.68, p < 0.001) for those who drank every day and 3-4 times a week, as compared to no consumption), but who drank 1-2 times/month is decreased risk of prediabetes (OR(adj) = 0.89, 95% CI, 0.82-0.97, p = 0.006). Similar findings were observed for men. Women who drank occasionally had a significantly decreased risk of pre-diabetes, compared with non-drinker in women (OR(adj) 0.95, 95% CI 0.91 0.99, p = 0.039). There was no interaction between alcohol consumption with other potential covariates. CONCLUSION: Alcohol consumption was independently associated with the risk of pre-diabetes in a possibly dose response fashion. Mild-moderate alcohol consumption appeared to be related with a decreased risk. PMID- 26817236 TI - Isolation, Identification, and Evaluation of Novel Probiotic Strains Isolated from Feces of Breast-Fed Infants. AB - OBJECTIVE: To isolate, identify, and evaluate the probiotic properties of lactic acid bacteria (LAB) isolated from the feces of breast-fed infants. MATERIAL AND METHOD: The probiotic tests included investigation of hemolysis activity, survival in simulated gastrointestinal tract conditions (acid and bile salt tolerance), susceptibility to antibiotics, and ability to inhibit selected bacterial pathogens (Escherichia coli O157:H7, Vibrio cholerae and Salmonella enterica subsp enterica serovar Typhimurium). The bacterial species identification was performed by both carbohydrate utilization and partial 16S ribosomal RNA sequencing. RESULTS: Five of fifty LAB isolates (UBU-03, UBU-06, UBU-09, UBU-34, and UBU-37) showed good probiotic properties. These five isolates showed non-hemolysis type (gamma-hemolysis), susceptibility to all antibiotics tested except for vancomycin, ability to survive in the simulated gastrointestinal conditions of both acid and bile salt solution, and ability to inhibit growth of E. coli O157: H7 and V. cholerae. Bacterial species identification revealed that all five isolates were firmly identified as Lactobacillus rhamnosus species. CONCLUSION: The L. rhamnosus strains that were isolated and characterized in this study could be considered as probiotic strains, and then used for further probiotic characterization in human cell cultures or animal models. PMID- 26817238 TI - Factors Related to the Sexual Behaviors among Youth in Universities Located in the Eastern Region of Thailand. AB - BACKGROUND AND OBJECTIVE: Youth is a "crisis period", as it is a transitional period between childhood and adulthood. This period incites the youth to have curiosity, especially to sexual contents. As a result, they have higher risk behavior leading to the percentage of newly HIV infected persons among youth in the eastern region that is proportionally higher. This research aimed to study factors related to sexual health behaviors among youth in universities located in the eastern region of Thailand. MATERIAL AND METHOD: This research was a cross sectional survey research. The data collection process was conducted from June September 2011. There were 405 informants, who participated in this study. They were students from both government and private universities in the eastern region. The age of the youth was 20-24 years old. The students' field of study varied. The tool of the study was self-answered questionnaires. The quantitative data were analyzed using descriptive statistics and presented as frequency, percentage, average score, deviation standard scale, and it was analyzed by Crude odds ratio. RESULTS: It was found that three-fifths of the youth already had sexual experiences, and more than half did not use condoms during their first time sex. Regarding sexual behavior, it was found that almost one-fourth of the students did not use condoms at any time when they had sex, and did not negotiate for safer safe when they had sex. The statistical significance was (p = 0.012, Crude OR = 1.65). Youth who already had sex had more chances to have unprotected sex than those who never had sex (p = 0.014, Crude OR = 1.64). Youth who had casual sex partner(s) had more chances to have unprotected sex than youth who did not have casual sex partner(s) (p = 0.026, Crude OR = 1.78). Youth who had little knowledge on AIDS and sexually transmitted diseases would have more chances to have unprotected sex than youth who had high level of knowledge on these topics (p = 0.010, Crude OR = 2.83). Youth who had negative attitudes towards safe sex would have more chance to have unprotected sex than youth who had positive attitudes towards safe sex (p = 0.002, Crude OR = 3.65). CONCLUSION: More than half of the informants had sexual experiences. They did not use condoms during their first-time intercourse. The study found that the factors, which had a relationship with sexual behaviors showing statistical significance, were as follows: gender, having sex in the past 3 months, having casual sex partner(s) in the past 3 months, knowledge on AIDS and sexually transmitted diseases, and attitude towards safe sex. This study's recommendation suggests that the educational institutions and parents should contribute to the knowledge and attitudes, and should support the life skills for safe sex behavior PMID- 26817239 TI - Antioxidant Activity and Cytotoxic Effect of Ventilago denticulata Willd Leaves Extracts. AB - BACKGROUND: Oxidative stress is characterized by an imbalance between the antioxidant defense systems and the formation of reactive oxygen species (ROS). The excess of ROS can damage biomolecules and leading to several chronic conditions and diseases such as diabetes, antherosclerosis, ischemic injury, inflammation and carcinogenesis. Plant extracts and their constituents as a natural source of antioxidants have been extensively studied. OBJECTIVE: The study aimed to investigate the antioxidant and cytotoxicity of aqueous and ethanolic Rhang Dang (entilago denticulata Willd) leaves extract. MATERIAL AND METHOD: The aqueous and ethanolic extracts of Rhang Dang leaves were preliminary analyzed for their phenolic profile (total phenolics and total flavonoids). These extracts were evaluated for their antioxidant properties by different methods such as DPPH radical scavenging andperoxyl radical scavenging activity generated by AAPH (2,2'-Azobis (2-methylpropionamidine) dihydrochloride). Their cytotoxic effects on hepatocellular carcinoma cell line (HepG2) and peripheral blood mononuclear cells (PBMC) were determined by MTT assay. Anti-hemolytic activity was examined using spectrophotometrical method. RESULTS: The ethanolic extract from Rhang Dang leaves exhibited a strong antioxidant activity and prevented hemolysis. It showed the highest amount of phenolics (91.03 +/- 12.43 mg of gallic acid equivalents/g extract) and flavonoid compound (69.76 +/- 10.84 mg of catechin equivalents/g). Interestingly, this extract was more cytotoxic to HepG2 cells than PBMC. CONCLUSION: The ethanolic extract from Rhang Dang leaves had strong antioxidant activity and cytotoxic effect on cancer cells. PMID- 26817240 TI - Iron-Chelating and Anti-Hemolytic Properties of Ethanolic Extract of Lotus (Nelumbonucifera Gaertn) Leaves. AB - BACKGROUND: Iron overload is the major consequence of blood transfusion in beta thalassemia patients. Redox iron plays a critical role in the formation of reactive oxygen species and subsequently leads to oxidative stress damage in many cells, especially red blood cells and hepatocytes. Iron deposition in hepatocytes is associated with fibrosis and cirrhosis. Polyphenolic compounds found in natural products are interesting iron chelators and antioxidants. OBJECTIVE: This study aims to evaluate the iron-chelating properties and free-radical scavenging activities of lotus leaf extract in iron-loaded HepG2 cells. MATERIAL AND METHOD: Lotus (Nelumbonucifera Gaertn) leaves were extracted with 80% (v/v) ethanol. The extract was examined for free-radical scavenging activity by using 2, 2-diphenyl 1-picrylhydrazyl assay (DPPH assay); iron-binding and anti-hemolytic activities using spectrophotometrical method. Iron-depriving activity of the extract was determined in iron loaded human hepatocellular (HepG2) cells using fluorescence technique. RESULTS: The lotus extract showed antioxidant and anti-hemolytic activities in a concentration-dependent manner. Furthermore, it was able to bind iron rapidly and was saturated within 10 minute. With 24-hour treatment, this extract dose dependently decreased the level of labile iron pool in iron loaded HepG2 cells. CONCLUSION: Lotus leaf extract had strong antioxidant activities, iron chelating properties on iron loaded HepG2 cells and anti-hemolytic activity. PMID- 26817242 TI - Comparative Studies of Structural and Functional Properties of Snake Venom Metalloproteinases. AB - Snake venom metalloproteinases (SVMPs) induces local and systemic effects on patients suffering from snakebite, degrading extracellular matrix (ECM) proteins such as collagen, gelatin, elastin, laminin, fibronectin, nidogen (entactin), and thrombospondin that cause local hemorrhage and tissue damage. They cleave or activate coagulation factors such as fibrinogen, fibrin, prothrombin, factor V, factor IX, factor X and protein C that bring about systemic coagulopathy. SVMPs and their truncated forms cleave or interfere with platelet adhesive proteins such as vWF, fibrinogen and collagen, and cleave or interfere with platelet receptors such as GPVI, alpha2beta1, GPIb, GPIX, and GPIIbIIIa that result in platelet aggregation defect. SVMPs induce cancer cell line to form morphological changes and apoptosis in vitro concordant with skin necrosis after snakebite in some cases. These local effects caused by SVMPs have no certain treatments, even with commercial anti-venom. SVMPs researches are focusing on their inhibitors, measurement and replacement of blood coagulation factor defects, or anti-cancer drug. PMID- 26817241 TI - Comparison of Automated and Conventional IHC Visual Scoring Analysis for MHC Class I and Tapasin Expression in Cervical Carcinoma. AB - BACKGROUND: Cervical cancer (CXCA) is the second most common cancer among women in Thailand and worldwide. Immune evasion caused by down-regulation of host immune responsive genes, such as MHC class I and loss of antigen processing machinery (APM), presents a capability leading to cancer development. Immunohistochemical staining (HC) is regarded as a common technique for protein marker detection in clinical laboratories. At present, IHC automation has been launched to facilitate the speed and feasibility to replace conventional IHC. However, evaluation of its use is still limited. OBJECTIVE: This study aimed to evaluate IHC scoring by automated visual analysis compared to conventional IHC analysis. MATERIAL AND METHOD: The paraffin-embedded tissues of 96 invasive CXCA were processed using a tissue microarray (TMA) platform followed by automated IHC staining of the anti-MHC class I (heavy chain, beta2M) and an APM-Tapasin expression. Conventional IHC and automated slide scanning with scoring visual analysis were compared. RESULTS: The results showed significant association between conventional and automated IHC evaluation (p-value > 0.05, Chi-square) for MHC class I and Tapasin stated in percentage of positive cancer cells, whereas intensity was found (p-value < 0.05, Chi-square) with moderate agreement (p-value < 0.001, kappa) 0.434-0.615 and 0.353-0.554, respectively. After calculated values, the results showed significant association between conventional and automated IHC evaluation (p-value > 0.05, Chi-square) for MHC class I and Tapasin with the highest agreement level (p-value < 0.001, kappa) of summation 0.595-0.755 and multiply scoring 0.633-0.689, respectively. CONCLUSION AND DISCUSSION: The automation softwarefor IHC scoring and interpretation can be used for the determination of MHC class I and Tapasin in CXCA. In addition, an antigen presentation pattern must be included to allow an accurate result for MHC class I in clinical use. An appropriate sample size and design of staging coverage as well as clinical prognosis outcomes of progression should be used infurther investigation. PMID- 26817243 TI - Overview: Detection of Human Papillomavirus in Clinical Samples. AB - Human papillomavirus (HPV) is the most common sexually-transmitted virus and it is known that persistent infection by high-risk HPV is a necessary factor for cervical carcinogenesis. Although cytological screening has decreased the incidence of cervical cancer, the sensitivity and specificity of testing is limited. To date, HPV-driven molecular techniques have provided a number of potential biomarkers for both diagnostic and prognostic use in clinical management. In addition, they can provide insights into the biology of HPV induced cancers leading to non-surgical therapy. This review summarizes current knowledge of detection methods for HPV and related biomarkers that can be used to discriminate lesions with a high risk of progression of cervical cancer. PMID- 26817244 TI - Nutraceutical for Autosomal Dominant Polycystic Kidney Disease Therapy. AB - Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder caused by mutations of either PKD1 or PKD2 gene. Cyst formation initiates from a combination of abnormal cell proliferation along with enhanced fluid secretion. ADPKD is characterized by the progressive enlargement of cysts which destroy the renal parenchymal cells, resulting in renal failure. Currently, there is no effective treatment for this disease. Interestingly, several relevant therapeutic effects of herbal medicine relevant to pathogenic process of ADPKD have urged the researchers to search for potential candidate herb as nutraceutical for ADPKD therapy. Up to now, several natural compounds, such as triptolide, curcumin, ginkolide B, and steviol (stevia extract) have been shown to be able to retard cyst progression in ADPKD. The detailed mechanism of these compounds showed that triptolide enhanced calcium restoration, curcumin inhibited ERK & p-STAT3 pathways, ginkolide B inhibited Ras/MAPK pathway, and steviol activated AMPK, which inhibited CFTR channel and mTOR pathway in cell and mouse models of PKD. In addition, they are currently inpreclinical and clinical studies, respectively. This review focuses on the pathophysiology of ADPKD and the recent therapeutic approaches, especially a potential use of nutraceutical for the treatment of autosomal dominant polycystic kidney disease. PMID- 26817245 TI - [Macroscopic and histopathological changes in the fetal appendages as a factor in the pathogenesis of intrauterine fetal death ]. AB - BACKGROUND: Intrauterine fetal death is an agonizing, often unpredictable event. Autopsies of stillborn fetuses, including placentas, umbilical cord and fetal membranes, are performed to clarify the cause of death. Autopsy results are not always easily understood by the patients and difficult to clarify by the specialists. OBJECTIVE: To evaluate the macroscopic pathological and histopathological changes in placenta, umbilical cord and fetal membranes as a factor in the pathogenesis of intrauterine fetal death. MATERIALS AND METHODS: Retrospective review of 129 autopsy reports of singleton stillborn fetuses and placentas from 23 to 41 weeks of gestation. RESULTS: Macroscopic and histopathological findings in the placenta, often in combination with inflammatory changes prevailing in premature cases, while macroscopic and histopathological findings in umbilical cord predominate in term stillborn. In 11% of cases there were no specific pathological findings. CONCLUSIONS: Pathological analysis of the placenta is essential for clarifying the pathogenesis of stillbirths. Simplifying the classification of pathological results of fetal appendages at autopsy categories--changes in the placenta, changes in the umbilical cord and inflammatory changes may contribute to easier interpretation and allows for comparison of results. PMID- 26817246 TI - [GYNECOLOGIC MALIGNANCIES DURING PREGNANCY]. AB - Cervical cancer is the most common gynecologic malignancy during pregnancy. Laparoscopic pelvic lymphadenectomy and the nodal status are the main factors to tailor therapeutic approaches and to terminate or preserve the pregnancy. In node negative pregnants neoadjuvant chemotherapy can be administered safely after 13 week of gestation in order to achive fetal maturity. In these cases, mostly in early stages, fertility- preserving techniques, such as vaginal simple or radical trachelectomy can be performed. PMID- 26817247 TI - [Human papillomavirus infection and pregnancy]. AB - There is growing evidence that HPV infection is possible through non-sexual routes like mother to-child transmission in the perinatal period. Human papillomavirus (HPV) infection has traditionally been regarded as a sexually transmitted disease (STD), but recent evidence implicates that an infected mother can transmit HPV to her newborn during pregnancy, at delivery, perinatal period or later. There is evidence of vertical transmission, presumably occurring during passage of the fetus through an infected birth canal. The virus could also be transmitted by ascending infection, principally after premature rupture of membranes. Elective cesarean delivery could not prevent transmission of the virus from HPV-positive mothers. There is insufficient evidence to recommend the generalization of cesarean section for all HPV DNA-positive mothers. The critical question is not how often infants are contaminated with HPV, but how often they are infected with HPV PMID- 26817248 TI - [SLOW RELEASED LOCAL PROBIOTICS]. AB - The probiotics are live microorganisms which embedded in adequate quantities have a healthy influence on the recipient. The current local probiotics get on medical practice at the beginning of the last decade and quickly become part of the current therapy of vaginal disbacteriosis and infections. A lot of studies show their microbiological and clinic effectiveness in prevention and treatment of the most met vaginal pathogens, usually together with on after pathogenetic or ethiological treatment. Slow release probiotics are the newest generation of probiotic products. Due to their limited and complicated pharmaceutical production, there are very few clinical trials on their microbiological and clinical effectiveness in the treatment of vaginal disbacteriosis and infections. Our expections for their useful application remain high, because of the already achieved good results. PMID- 26817249 TI - [Saforelle - a new approach to treat vaginitis]. AB - Infections of the vulva and vagina are one of the most common gynecological diseases. They can be determined by a variety of physical, chemical and biological factors. The main risk factors contributing to vaginitis are aerobic and anaerobic bacterias, fungal and viral infections, and irritants. Subjective complaints are pruritus, vulvar and/or perivulvar erytema and different in volume and characterization discharge. Excepting etiological treatment in most cases it is necessary to use additional agents, for example Saforelle. PMID- 26817250 TI - [ASSOSSIATION BETWEEN UNEMPLOYMENT, HEAVY PHYSICAL WORK AND PREMATURITY: RESULTS OF CASE-CONTROL STUDY IN PLEVEN]. AB - INTRODUCTION: Many studies confirmed the lower risk of prematurity among working women and established a link between heavy physical work and the prematurity. The aim of the study is to establish the association between unemployment and the heavy physical work of the mother during pregnancy and the birth of a premature baby. MATERIAL AND METHODS: In 2011 case-control study of two groups of premature (58) and mature (192) children born in 2007 in the University Hospital "George Stransky"--Pleven was conducted. For the aim of the study documentary method and sociological interview were used. The survey data were processed with statistical software packages. The significance of the results, findings and conclusions determined at p < 0.05. Odds ratio (OR) was used for assessment the strength of the association. RESULTS: In this study we found: more than four times higher risk of giving birth to a premature baby for unemployed mothers (OR = 4.48; 95% C = 2.56-7.83; P = 0.01); more than two times higherrisk of premature child birth among mothers performing heavy physical work during pregnancy (OR = 2.40; 95% CI = 1.03-6.19; P = 0.050) and the protective effect of having a job during pregnancy in association to the birth of a premature baby (OR = 0.26; 95% CI = 0.15-0.45; P = 0.001). CONCLUSION: We confirm our hypothesis that the unemployment and the heavy physical work during pregnancy increase the risk for birth of a premature baby PMID- 26817251 TI - [Instant teas - new formulations]. PMID- 26817252 TI - [Nutrition during pregnancy]. PMID- 26817253 TI - [Pregnancy and obstetric delivery by women with paroxysmal hemoglobinuria nocturnal - a case report]. PMID- 26817254 TI - [Problems with the professional performance of the nurse midwives in the hospitals]. PMID- 26817255 TI - [The quality of midwifery during the postpartum period]. PMID- 26817256 TI - [CLINICAL PERFORMANCE OF DIFFERENT METHODS FOR CERVICAL SCREENING]. AB - Cervical cancer is a serious medical and social issue as it affects women at active age and it is diagnosed too late. In Bulgaria morbidity and mortality show continuous increasing trend. The aim of this study is to compare the clinical performance of cytology and other alternative methods for cervical screening that could be used to assess the the cervix. MATERIAL AND METHODS: This is a prospective study which included 317 patients aged between 18 and 65 years. Women were divided into four groups: I-st--cytology, Il-nd--visual inspection with acetic acid (VIA), III-th--visual inspection with Lugol's iodine (VILI) and IV-th -spectrophotometric analysis with TruScreen(r). The results showed that the most appropriate screening method for cervical cancer remains cytology. In the absence of cytological laboratory or cytopathologist spectrophotometric analysis with TruScreen(r) can be used for primary cervical screening. Its main advantages are that it is a real time technique, user easy and it is well accepted by women. If TruScreen is not available in the gynecologist's practice it is possible to perform visual inspection with acetic acid (VIA). PMID- 26817257 TI - [THYROID STIMULATING HORMONE LEVELS IN EUTHYROID WOMEN WITH POLYCYSTIC OVARY SYNDROME]. AB - The purpose of this study was to analyze the relationship of the main hormonal and metabolic abnormalities in PCOS with different levels of TSH in the limits of its reference values. MATERIAL AND METHODS: The study involved 70 women with PCOS aged 16 to 39 years and BMI between 18.3 and 39.5 kg/m2 and a control group of 22 clinically healthy women, corresponding to age and BMI. In all of the participating women fasting plasma glucose, total cholesterol, HDL-cholesterol, triglycerides, insulin, TSH, FT4, TPO-Ab and Tg-Ab, LH, FSH, estradiol, Androstenedione, testosterone, SHBG, DHEA-S, prolactin, 17-hydroxyprogesterone were assessed. BMI, LDL-cholesterol, LH/FSH ratio, FAI and HOMA-index were calculated. RESULTS: In patients with PCOS, TSH levels > 2.0 mlU/L are associated with significantly higher levels of total and LDL-cholesterol. However, we did not find a direct dependency of TSH indicators of insulin resistance neither across the group of women with PCOS, nor with the subgroups. Therefore, in euthyroid women with PCOS TSH has a more pronounced effect on lipid compared to carbohydrate metabolism and in particular on insulin sensitivity. CONCLUSION: TSH levels above 2.5 in patients with PCOS are a sign for further refinement of thyroid function, initiation or adjustment of the already commenced replacement therapy. PMID- 26817258 TI - [PROGNOSTIC SIGNIFICANCE OF ADJUVANT RADIOTHERAPY IN EARLY IB1 STAGE CERVICAL CANCER]. AB - The cervical cancer is one of the most common malignancies. Worldwide 500,000 women a year become ill from cervical cancer. The aim of the study was to establish the role of adjuvant radiotherapy in patients with IB1 cervical cancer in terms of disease free survival. Between 2002-2012, 132 patients diagnosed as IB1 stage according to FIGO criteria were enrolled in the study. Depending on the administered therapy the patients were divided into two groups--Group 1-93 patients were treated surgically and with adjuvant radiotherapy and Group 2--39 patients were treated surgically without adjuvant radiotherapy Surgery was radical hysterectomy class III and pelvic or paraaortic lymph node dissection(in cases of bulky paraaortic nodes), and adjuvant RT-telegamma therapy(TGT) in dose 52 Gy. The frequency of recurrence in a Group I (surgery and TGT) is 9.7%. Tree and five years disease free survival (DFS) is 88%. The frequency of recurrence in a Group 2 (surgery without TGT) is 25.6%. Tree and five years DFS respectively are 70% and 65%. In an analysis of oncological results establish that adjuvant TGT after surgery significantly increases DFS. On the other hand the addition of adjuvant TGT increases the patients morbidity Therefore should determine which are the risk factors for the occurrence of relapses and select group of patients who would benefit from adjuvant TGT and the risk of complications in them would be justified. PMID- 26817259 TI - [LOCALIZATION AND SIZE OF THE LESIONS IN PELVIC ENDOMETRIOSIS]. AB - OBJECTIVE: The study aimed to describe localization and size of the lesions in pelvic endometriosis MATERIAL AND METHODS: A retrospective study was carried out including 375 patients with pelvic endometriosis who were operated in St. Marina Hospital-Pleven from January 2008 to July 2014. RESULTS AND DISCUSSION: The ovaries are the pelvic organs most affected (76%) by endometriosis, the lesions being usually 4-5 cm in size. Peritoneal endometriosis ranks second, with 58.2%, and the rarest is DIE with 0.5%. CONCLUSION: Localization, number and size of the endometriosis lesions determine the severity of the condition. These parameters are crucial for making decisions concerning the type and extent of surgical intervention. PMID- 26817260 TI - [PROGNOSTIC GROUPS FOR RELAPSE IN STAGE IB1 CERVICAL CANCER]. AB - Risk factors for relapse in stage IB1 cervical cancer were analized and identified by the following statistical tests-Kaplan-Meier, Cox regression, Log rank test, Breslow and Tarone-Ware tests. A quantitative analysis of significant factors for relapse in group submitted to surgery and adjuvant radiotherapy(group 1) and group submitted only to surgery (group 2), was done. These methods allow us to difine 3 different prognostic groups, requiring different therapeutic approaches. PMID- 26817261 TI - [THE ROLE OF THE CYTOKINE PROFILE IN TREATMENT IN WOMEN WITH ENDOMETRIAL CANCER FIRST STAGE]. AB - Endometrial canceris the most common gynecological cancer. It is positive that more than 53% of diagnosed cases of endometrial cancer are in first stage when the therapeutic options are more successive. More and more gynecologists in addition to the normal clinical and histological tests expand the information for the neoplastic process with biochemical and immunological markers-tumor markers, hormones, lymphocyte population, cytokines, markers for lesion-inflammatory processes, etc. Several biological mechanisms track the connection between overweight and endometrial neoplastic risk. In the surgical practice is increasing the interest towards the cytokine group as independent prognostic factors, aggressiveness and options for treatment of the neoplastic process. The cytokine profile can be used as factor for evaluation of the primary neoplastic immune impairment as well as for a choice of surgical intervention. This is extremely important for obese patients because obesity is turning into worldwide medico-social problem. PMID- 26817262 TI - [VAGINAL LEIOMYOMA AFTER TOTAL ABDOMINAL HYSTERECTOMY--CLINICAL CASE AND REVIEW OF LITERATURE]. AB - Vaginal myomas are rare benign, mesenchyme, monoclonal tumors. They originate from smooth muscle cells and have a diverse and non-specific clinical feature. They are normally presented as single solid nodules localized in anterior vaginal wall in women between the ages of 35-50 years. Often times they are secondary originating from a cervical or vaginal lesion in woman who had undergone a hysterectomy on account of a myoma. We present a rare case of vaginal myoma localized in the posterior vaginal wall in a patient, who had undergone a total hysterectomy 19 years ago on account of a myoma. PMID- 26817263 TI - [MALIGNANT MELANOMA--THE INFLUENCE OF HORMONAL FACTORS ON THE PROGRESSION AND PROGNOSIS. COMPARATIVE ANALYSIS BASED ON TWO CLINICAL CASES]. AB - Malignant melanoma is the most aggressive form of skin cancer showing extremely high metastatic rate and leading to high levels of lethality. The continually growing incidence of malignant melanoma in the world and his difficult early diagnosis are the occasion for numerous studies. The individual risk for malignant transformation of melanocytes is determined by a number of etiologic factors--endogenous and exogenous. Ultraviolet radiation has a leading role in the group of exogenous factors. Within the group of endogenous factors, besides the well-known photo type skin, as well as genes mutations, are added and the sex hormones, with their significant prognostic importance. The differences, which are observed in the progression and prognosis of malignant melanoma in pre- and postmenopausal women, and men, have defined this cutaneous neoplasma as hormone dependent tumor. We present two seemingly similar clinical cases of 52 year old woman and 53-year-old man diagnosed with malignant melanomas, developed on the basis of pigmented lesions located on the upper back, as we attempt a comparative analysis on etiopathogenetic factors led to radically different course and prognosis of the disease in these two patients. PMID- 26817264 TI - [LAPAROSCOPIC MYOMECTOMY WITH UTERINE ARTERY CLIPPING VERSUS CONVENTIONAL LAPAROSCOPIC MYOMECTOMY]. AB - Uterine leiomyomas are one of the most common benign smooth muscle tumors in women, with a prevalence of 20 to 40% in women over the age of 35 years. Fifty percent of them may necessitate treatment, because of bleeding, pelvic pain and infertility. Laparoscopic myomectomy is one of the treatment options. The major concern of myomectomy either by open procedure or by laparoscopy is the bleeding encountered during the operation. One of the methods to reduce the intraoperative blood loss and to prevent excessive bleeding is the clipping of both uterine arteries and aa. ovaricae. PMID- 26817265 TI - Editorial. PMID- 26817266 TI - The Risks and Rewards of Value-Based Reimbursement. AB - As healthcare systems across the country shift to value-based care, they face an enormous challenge. Not only must they reimagine how they identify, engage, and manage the care of patients, they also need to determine new ways of engaging and aligning physicians and other caregivers in creating better-coordinated care across the continuum. This article explores how healthcare systems making the transition from volume to value can maximize their reward while managing their risk. As the largest not-for-profit healthcare system in the United States and the largest Catholic healthcare system in the world, Ascension is committed to making its own transition, marked by broad-based innovation. We call this goal the Quadruple Aim: improving health outcomes, patient experiences, and provider experiences while lowering the overall cost of care. Healthcare systems and providers have many value-based models to choose from, including pay for performance (P4P), shared savings, bundled payments, shared risk, global capitation, and provider-sponsored health plans. Analysis of these options should include an evaluation of market readiness (i.e., the ability of a health system to align with the needs of employers or commercial insurers in a given market). Healthcare systems also must be prepared to invest in resources that facilitate effective transitions and continuity of care--for example, care management. In addition, they need to recognize that as they focus on wellness, inpatient volumes will decline, requiring cost-structure adjustments and added ancillary services to compensate for this decline. Some healthcare systems are even exploring the possibility of becoming their own payer, taking on more risk and responsibility for the health of patients and populations. PMID- 26817267 TI - Value-Based Reimbursement: The Banner Health Network Experience. AB - Many organizations in healthcare are moving rapidly to adopt value-based reimbursement (VBR) models that reward value instead of volume. By shifting a significant percentage of clinical and financial risk from payers to providers, VBR programs can help reduce costs significantly, improve the quality of care, and increase efficiency. The experience of Banner Health Network (BHN) with VBR in commercial and government plans indicates that a large health system can transition to VBR with renewed focus on quality, cost efficiencies, population health management tactics, and member engagement. In December 2011, BHN was selected in a competitive bid process as one of 32 organizations to participate in a Centers for Medicare & Medicaid Services (CMS) value-based demonstration initiative called the Pioneer accountable care organization (ACO). As a Pioneer ACO with consistent and positive results, BHN, based in Phoenix, Arizona, has demonstrated that VBR can lead to results that are beneficial to the member, the healthcare organization, and the community. BHN has been a top performer in returning shared savings to Medicare while improving appropriate service utilization and performance on quality metrics. The development of simultaneous commercial ACO products was a requirement of the Pioneer agreement with CMS, as well as a clear goal for BHN. The initial period of ACO partnership formation revealed an uncomfortable reality: Payers and providers would need to collaborate and share information as never before. Further, many payers were uncertain about working closely with providers who were working simultaneously with other payers on similar partnerships. Before long, however, there were enough successful VBR arrangements to allay these initial payer anxieties. Today, BHN has high-value network arrangements with nearly every major payer in Arizona. PMID- 26817268 TI - Now or Never: Making the Commitment to Value-Based Reimbursement. PMID- 26817269 TI - Value-Based Payment: Supporting an Intertwined Clinical-Business Model. PMID- 26817270 TI - Moving Toward Value-Based Care and Payment. PMID- 26817271 TI - Progress in the study of drug nanocrystals. AB - The poor water solubility of many candidate drugs remains a major obstacle to their development and clinical use, especially for oral drug delivery. Nanocrystal technology can improve the solubility and dissolution rates of many poorly water-soluble drugs very effectively, significantly improving their oral bioavailability and decreasing the food effect. For this reason, this technology is becoming a key area of drug delivery research. This review presents much of the recent progress in nanocrystal drug pharmaceuticals, including the characteristics, composition, preparation technology, and clinical applications of these drugs. Finally, the effect of nanocrystal technology on insoluble drugs is quantified and described. PMID- 26817272 TI - Pharmacological activities and structure-modification of resveratrol analogues. AB - Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a well-known natural polyphenol compound. It is reported that resveratrol possesses strong anti-oxidative, anti inflammatory, cardiovascular protective and cancer chemo-preventive effects. Therefore, there has been a considerable interest in its biological activity, pharmacological activity and also synthetic resveratrol analogues in recent years. Up to now, many new resveratrol derivatives have been synthesized and some new biological activities of these compounds have been found, so in the treatment of Alzheimer's disease and the inhibition of influenza H1N1 neuraminidase. Structure-activity studies revealed that crucial elements of parental components are required for specific effects. This review summarizes the available literatures on the structure-activity relationships and pharmacological properties of resveratrol analogues. PMID- 26817273 TI - Synthesis and biological evaluation of 2,6-di(furan-3-yl)anthracene-9, 10-dione as an inhibitor of human protein kinase CK2. AB - Protein kinase CK2 is an emerging target for the therapeutic intervention in human diseases, in particular in cancer. Inhibitors of this enzyme are at current in clinical trials indicating its drug ability. Here we report on the synthesis of two derivatives of 2,6-diaryl-anthracene-9,10-dione, one of them, 2,6-di(furan 3-yl)anthracene-9,10-dione (3), turned out to be active towards CK2, and ATP competitive with an IC50 value of 2.35 MUM and a K(i) value of 1.26 MUM. Molecular modeling studies were performed to explain the binding affinity of compound 3 in comparison to emodin. These indicated that unlike emodin, compound 3 was not able to perform a hydrogen bond with Lys68, although the compound fits well in the active site of human CK2alpha, which explains the difference in the measured affinity between those two compounds. PMID- 26817275 TI - The effects of surfactants on the solubility and dissolution profiles of a poorly water-soluble basic drug, carvedilol. AB - This study investigated the most suitable surfactant medium for the dissolution testing of a poorly soluble basic drug, namely, carvedilol reflecting the in vivo behavior. Sodium lauryl sulfate (SLS), hexadecyltrimethylammonium bromide (CTAB) and polysorbate 80 were used as anionic, cationic and nonionic surfactants, respectively. Saturation solubilities of carvedilol were determined in the presence of SLS, CTAB and polysorbate 80 (0.5, 1 and 2% (w/v)) at pH 1.2 and 6.8. Dissolution behaviors of the commercial tablets were studied using USP apparatus II in pH 1.2, 4.5 and 6.8 buffers and pH 6.8 dissolution media with 0.5% (w/v) SLS, polysorbate 80 and CTAB. Polysorbate 80 enhanced the solubility of carvedilol irrespective of pH, while SLS and CTAB exhibited larger solubilization effect than polysorbate 80 depending on pH and the ionic nature of the surfactant. Based on in vitro dissolution profile similarity, pH 6.8 dissolution medium with 0.5% (w/v) polysorbate 80 was found to be the most biorelevant medium, which probably reflects the bioequivalence of test products to the reference product of carvedilol. PMID- 26817274 TI - Identification of 2-substituted ethenesulfonic acid ester derivatives as novel, potent and selective inhibitors of protein tyrosine phosphatase 1B. AB - Sixteen 2-substituted ethenesulfonic acid ester derivatives were designed, synthesized and evaluated for the inhibitory activity against tyrosine phosphatase 1B (PTP1B) and T-Cell protein tyrosine phosphatase (TCPTP). The structural activity relationship (SAR) of these compounds demonstrated that the hydrophilic head, aromatic center and the hydrophobic tail affected the inhibitory activities against PTP1B and the selectivity over TCPTP. Most of the compounds exhibited excellent inhibitory activity against PTP1B with IC50 value of 1.0 MUM - 31.2 MUM. SAR analysis revealed that the hydrophilic head was indispensable in the maintain of inhibitory activity against PTP1B, the aromatic center significantly altered the selectivity of PTP1B over TCPTP, and the hydrophobic tail significantly altered the inhibitory activity against PTP1B. PMID- 26817276 TI - Enhanced bioavailability of raloxifene hydrochloride via dry suspensions prepared from drug/HP-beta-cyclodextrin inclusion complexes. AB - This study aimed to develop a dry suspension formulation of raloxifene (RLX) using its HP-beta-cyclodextrin inclusion complexes to enhance the oral bioavailability. Dry suspensions loading RLX/HP-beta-cyclodextrin inclusion complexes (RLX-HICs) were prepared by solvent evaporation followed by a standard wet granulation process. The inclusion complexes were characterized by scanning electron microscopy, differential scanning calorimetry, and Fourier transform infrared spectroscopy. The features of dry suspensions such as dispersibility, flowability and dissolution were compared with conventional suspensions. Dry suspensions containing RLX-HICs dramatically increased the dissolution of RLX. Pharmacokinetic studies in rats showed that dry suspensions with RLX-HICs significantly enhanced the oral bioavailabilities of RLX. The absolute and relative bioavailabilities were up to 13.04% and 413.97% compared with the solution formulation (i.v.) and conventional suspensions (i.g.), respectively. The bioavailability improvement for dry suspensions with RLX-HICs can be attributed to improved dissolution and physiochemical properties of RLX, by which the overall absorption was enhanced. Dry suspensions prepared from RLX-HICs may be an attractive formulation for the oral delivery of RLX. PMID- 26817277 TI - The influence of passage number for Caco2 cell models when evaluating P-gp mediated drug transport. AB - Caco2 cells are a human adenocarcinoma cell line that forms tight junctions and are widely used to examine bidirectional drug transport as well as P-glycoprotein mediated efflux. Unfortunately Caco2 cell lines can be very heterogeneous in nature. Our aim was to improve the Caco2 cell model for determination of P glycoprotein mediated drug transport. Young passage Caco2 from ATCC had inadequate expression of P-glycoprotein, therefore three approaches were adopted to upregulate Caco2 P-glycoprotein expression to mimic that in vivo; a) incubation of mature Caco2 monolayer with rifampicin, b) prolonged exposure of Caco2 cells to vinblastine (generating the Caco2 VIN line), and c) splitting cells every 7 to 9 days until late passage numbers (over P80) were available. Upon development of the models, P-gp expression and activity was determined using western blotting and bidirectional transport studies of rhodamine123. All four models exhibited P-gp mediated efflux transport for rhodamine123. Incubation with rifampicin did not alter bidirectional transport compared to passage 44 cells. Increased passage number altered P-glycoprotein expression and the efflux ratio increased to 4.7 for passage 80 from 1.4 of passage 44. The highest basolateral to apical transport was observed for both passage 89 Caco2 and the Caco2 VIN model with an efflux ratio of 13 to 14. Western blot images confirmed the increased P-glycoprotein expression of late passage and Caco2 VIN. Caco2 cells are not ready for P-gp related research when first acquired from ATCC (Passage 18). Late passage Caco2 cell monolayers or Caco2 VIN models are needed to determine P-gp mediated efflux transport. PMID- 26817278 TI - Icariin promotes expression of junctophilin 2 and Ca2+ related function during cardiomyocyte differentiation of murine embryonic stem cells. AB - Junctophilin2 (JP2) is a critical protein associated with cardiogenesis. Icariin (ICA) facilitated the directional differentiation of murine embryonic stem (ES) cells into cardiomyocytes. However, little is known about the effects of ICA on JP2 during cardiac differentiation. Here, we explored whether ICA has effects on the expression and Ca2+ related function of JP2 during cardiomyocyte differentiation of ES cells in vitro. Embryonid bodies (EBs) formed by hanging drop were treated with 10(-7) mol/L ICA from day 5 to promote the cardiac differentiation. Percentage of beating EBs and number of beating area within EBs were monitored. Cardiomyocytes were purified by discontinuous percoll gradient centrifugation from EBs. The expression of JP2, alpha-actinin and troponin-T within EBs or isolated cardiomyocytes were analyzed by immunocytochemistry, western blot and flow cytometry. The transient Ca2+ release was characterized in cardiomyocytes treated with/without 10 mmol/L caffeine and 8 mmol/L Ca2+. Our results showed that ES cell-derived cardiomyocytes were well characterized with JP2 proteins. ICA promoted cardiomyocyte differentiation as indicated by an increased percentage of beating EBs and number of beating area within EBs. The expression of JP2, alpha-actinin and troponin-T were up-regulated both in EBs and isolated cardiomyocytes from EBs. Furthermore, ICA-induced JP2 expression was accompanied by a remarkable increase of the amplitude of Ca2+ transients in cardiomyocytes before/after caffeine and Ca2+ stimulating. In conclusion, ICA promotes in cardiac differentiation partly through regulating JP2 and improved the Ca2+ modulatory function of cardiomyocytes. PMID- 26817279 TI - Anti-platelet and anti-thrombosis characteristics of Z4A5, a novel selective platelet glycoprotein IIb/IIIa inhibitor, compared with eptifibatide under long term infusion. AB - Platelet Glycoprotein IIb/IIIa inhibitors are approved for the treatment of acute coronary syndromes and percutaneous coronary interventions due to their effects on the final common pathway of platelet aggregation. Z4A5 is a new hexapeptide IIb/IIIa inhibitor with antiplatelet and antithrombotic effects. This study was performed to assess the characteristics of Z4A5 compared with another IIb/IIIa inhibitor eptifibatide. Light-transmission aggregometry was used to measure platelet aggregation to assess the antiplatelet efficacy of Z4A5 in vitro and ex vivo in beagles. The time course of platelet inhibition and bleeding time prolongation during i.v. bolus plus infusion and after infusion of the Z4A5 were evaluated in beagles following two 2 x 2 Latin square designs. We also compared the antithrombotic activity of Z4A5 with eptifibatide in arterial thrombosis and arteriovenous shunt thrombosis model in beagles. Our data showed that Z4A5 completely inhibited adenosine diphosphate (ADP)-, thrombin- and arachidonic acid induced in vitro platelet aggregation with values of IC50 of 260 nM, 128.6 and 56.4 n respectively. Z4A5 also markedly and stably prevented ADP-induced ex vivo platelet aggregation and prolonged the bleeding time throughout the 8-hour infusion. Both platelet function and bleeding time returned to normal sooner after cessation of Z4A5 infusion than after eptifibatide. Z4A5 inhibited thrombosis and had the same potent antithrombotic activity as eptifibatide. In conclusion, Z4A5 has the same potent antiplatelet effect and antithrombotic activity with the advantage of a faster on and off time compared to eptifibatide. PMID- 26817280 TI - A non-invasive CYP3A4 biomarker and body mass index predict cyclosporine dosage requirements in Chinese renal transplant recipients. AB - An endogenous CYP3A4 biomarker for in vivo metabolism of cyclosporine should be useful for optimizing individual dosage. We aimed to investigate if the combined ratio of endogenous 6beta-hydroxycortisol and 6beta-hydroxycortisone to cortisol and cortisone (HOM) in urine could be used as an endogenous probe for the prediction of cyclosporine dosage requirements in renal transplant recipients. 54 medically stable kidney transplant recipients participated in this study. Morning spot blood and urine samples were gathered. The multiple regression analysis including urinary HOM and body mass index accounted for 73.1% of variability in blood concentration/dose ratio (C/D) of cyclosporine, in which urinary HOM and body mass index contributed 64.9% and 8.2%, respectively. Based on the present approach, individual dosage regimen of CsA could be acquired without therapeutic drug monitoring and the results showed that all of the observed stable doses of CsA were within the predicted range during different post-operative periods. In summary, there is a significant relationship between endogenous CYP3A4 biomarker (assessed by urinary HOM) and in vivo metabolism of cyclosporine in renal transplant recipients. Urinary HOM and body mass index are important predictors of cyclosporine metabolism. Our findings provide clinical implications that the predictive algorithm based on a simple, safe and non-invasive CYP3A4 phenotyping can be anticipated. PMID- 26817281 TI - The Doolin Lecture 2015: 5th December 2015; 'The Patient Experience as a Catalyst for Change'. PMID- 26817282 TI - Mental Health Policy in Ireland: A Decade after A Vision for Change, Where Are We Now? PMID- 26817283 TI - Paediatric Early Warning Trigger--A Cry for Help. AB - In paediatrics, it is crucial to ensure that the child who is clinically deteriorating is rapidly recognised and treated. We implemented a Paediatric Early Warning Trigger (PEWT) in our unit to improve recognition of these patients. Our trigger was a series of physiological measurements with a PEWT call if any result was outside the accepted range. We retrospectively compared 12 months prior to the introduction of the trigger (January to December 2009) to the three years post the introduction of the trigger (January 2010 to December 2012). We compared the time from deterioration to involvement of senior staff during the two time periods. We also examined the rates of crash calls and PICU transfers in the two periods. We found that the time from deterioration to senior clinician involvement reduced from 312 minutes to 166 minutes and the rate of transfers to PICU among the triage category 1 & 2 patients reduced from 1:50 in 2009 to 1:129, 1:118 and 1:131 during the three years of the trial. The rate of cardiac arrest among this group reduced from 1:100 in 2009 to 1:129, 1:216 and 1:542 during the three years of the trial. This study demonstrates the effectiveness of a Paediatric Early Warning Trigger in an Irish setting. We have been able to maximise senior clinician input into our sickest children in a more timely fashion PMID- 26817284 TI - The Role of Speech and Language Therapy in Assessing and Managing Pharyngo esophageal Diverticula. AB - This study explores the contribution of Speech and Language Therapists (SLTs) to the assessment and management of patients presenting on videofluoroscopic swallow studies (VFSS) with a suspected pharyngo-oesophageal diverticulum. Records for all patients who attended for VFSS in an acute hospital over an eleven-year period were examined (N = 1820). Twenty patients were identified on VFSS as having a suspected diverticulum. Symptoms suggestive of a diverticulum were found during both bedside clinical examination and radiographic examination e.g. respiratory difficulties (n = 15; 75%), voice changes (n = 14; 70/0). VFSS confirmed a reduced risk of aspiration for 14 patients (70%) using a combination of fluid modification (n = 9; 45%), food modification (n = 13; 65%) and swallow strategies (n = 14; 70%). VFSS confirmed aspiration directly related to the diverticulum in 11 patients (55%). Findings indicate that SLTs have the opportunity to identify potential diverticula and implement behavioural management to reduce associated health risks. This is of particular importance to patients who are awaiting, or cannot undergo, surgical repair of their diverticulum. PMID- 26817285 TI - Utilisation of Clinical Networks to Facilitate Elective Surgical Workload; A Preliminary Analysis. AB - Clinical networks have potential to increase elective surgical workload for benign conditions in non-cancer centres. The aims of this study were to determine outcomes for elective laparoscopic cholecystectomy in our unit and to evaluate early experience in managing benign surgical workload referred from the tertiary centre within our clinical network. An analysis of cholecystectomies performed at Mayo General Hospital was conducted (2003-2013). A review of elective procedures more recently referred from Galway University Hospital (GUH) waiting lists was also conducted. 1937 consecutive cholecystectomies were performed with an overall laparoscopic conversion rate of 1.7% (33/1875). The total major complication rate was 0.93% (18/1937). 151 selected procedures originating from GUH have been performed since December 2013 without adverse events. Laparoscopic cholecystectomy can be performed in significant volume in the general hospital environment. This and other appropriate benign surgical procedures may be performed outside of tertiary units according to network agreements. PMID- 26817287 TI - Safety of Grass Pollen Sublingual Immunotherapy for Allergic Rhinitis in Concomitant Asthma. AB - Seasonal allergic rhinitis (AR) occurs predominantly as a result of grass pollen allergy. Grass pollen sublingual immunotherapy (SLIT) has been proven effective in treating AR1. SLIT is currently licensed for use in AR with concomitant stable mild asthma. There is evidence that SLIT improves asthma control when primarily used to treat AR2. The aim was to assess the safety of SLIT in patients with severe seasonal allergic rhinitis who have co-existing stable mild asthma. The secondary aim was to determine whether asthma control improved post SLIT. There was no deterioration in asthma control after 6-36 months of SLIT. 27/30 (90%) patients' asthma control remained stable or indeed improved (p < 0.021). Of this 15 (50%) patients' asthma improved. There was no statistically significant change in their asthma pharmacotherapy after SLIT (p = 0.059). In conclusion, grass pollen SLIT is safe and can potentially treat dual allergic rhinitis- mild asthmatic patients. PMID- 26817286 TI - Added Value of Stroke Protocol MRI Following Negative Initial CT in the Acute Stroke Setting. AB - The aim of the study was to determine the added value of stroke protocol MRI following negative initial CT brain in the acute stroke setting. A retrospective study was performed over a 6 month period in a tertiary referral stroke centre. Patients were selected from the stroke and radiology databases. Inclusion criteria: clinical stroke syndrome, negative initial CT with subsequent MRI study with diffusion weighted sequences. Ninety two patients were reviewed and 73 (M:F of 39:34, mean age 62.1 +/- 14.0 years) met the inclusion criteria. Twenty MRI studies (27.4%) were positive for acute/subacute ischaemia in the setting of a normal initial CT. The average time interval between initial CT and MRI brain imaging was 4.7 +/- 2.6 days. Whilst CT continues to be the first line imaging investigation for acute stroke, MRI has substantial added value following negative initial CT in the diagnosis of stroke. PMID- 26817288 TI - Young, Male and Feeling Suicidal in Ireland: Is Help or Harm Just One Click Away?. AB - Reports suggest an association between internet use and the elevated risk of suicide and self harm. This study examined the resources a suicidal person might find when searching the internet 'front page' for help. Voluntary suicide help websites accounted for 7/12 front page hits. The National Suicide Research Foundation (NSRF) and the National Office for Suicide Prevention (NOSP), a blog and a newspaper article made up the remainder. Sites were difficult to navigate and highly variable in content. Phone credit was required in many cases in order to contact helplines; opening hours and locations were limited. Most statutory websites referred help-seekers to the voluntary sector, mainly the Samaritans. Information on fundraising and volunteering competed with other sources of help. Of concern, the front page also included links to methods to complete suicide. Irish professional medical bodies offered very limited advice. Our findings suggest that online information is variable and potentially harmful. There is an opportunity for all agencies and providers to generate a co-ordinated internet front page tailored for at-risk groups. PMID- 26817289 TI - Pregabalin Abuse amongst Opioid Substitution Treatment Patients. AB - Pregabalin (Lyrica(r)) is used in treating epilepsy, nerve pain and anxiety. Pregabalin was initially thought to have a low misuse potential however there are emerging reports of Pregabalin being abused. A study was commenced at the National Drug Treatment Centre's (NDTC) Drug Analysis Laboratory to determine the level of usage of Pregabalin within the addiction services population in Ireland. A total of 498 urine samples representing samples from 440 individual opioid substitution patients, initially screened by immunoassay for drugs of abuse, were subjected to further analysis for Pregabalin by Liquid Chromatography/Mass Spectrometry (LC/MS). Of 440 patients tested, 39 tested positive for Pregabalin (9.2%). Only 10 patients from this group were prescribed this drug to our knowledge thus giving an estimated rate of misuse of 7.0%. Other drugs detected in the Pregabalin positive patients were Opiates (31.8%), Cocaine (11.4%), Benzodiazepines (79.5%) and Cannabis (77.8%). Our study confirms that Pregabalin abuse is taking place amongst the addiction services population. We believe that misuse of this prescription drug is a serious emerging issue which should be monitored carefully. PMID- 26817290 TI - Post traumatic Fat Embolism in Common Femoral Vein on CT. AB - Fat embolism syndrome usually occurs following trauma where fat globules from long bone fractures produce pulmonary, cerebral or cutaneous effects. This case illustrates the presence of macroscopic fat in the right common femoral vein secondary to a long bone fracture. This finding is rare but should be looked for on cross-sectional imaging to allow early, aggressive treatment of fat embolism syndrome. PMID- 26817291 TI - Association of Oesophageal Hypertension with Bradycardia Mediated Deglutition Syncope. AB - Swallow syncope is a rare form of situational syncope. We report a case of swallow syncope with invasive confirmation of esophageal hypertension (spasm) and invasive confirmation of a bradycardia mechanism. Awareness of this uncommon disorder is important as a treatable cause of syncope. PMID- 26817292 TI - 'Malignant Phenylketonuria' (PKU) Due to Dihydropteridine Reductase (DHPR) Deficiency. AB - DHPR deficiency is a rare autosomal recessively inherited metabolic disorder of tetrahydrobiopterin (BH4) regeneration. Clinical symptoms may comprise microcephaly, developmental delay, ataxia and seizures. BH4 is the cofactor for the enzyme phenylalanine (Phe)hydroxylase (PAH), and for tryptophan and tyrosine hydroxylases, both of which are essential for serotonin and dopamine biosynthesis. We present four patients in two families who are being treated at the National Centre for Inherited Metabolic Disorders (NCIMD). All are members of the Irish Traveller population. We have identified a homozygous mutation, c.353C>T, in the DHPR (QDPR) gene which, to the best of our knowledge, has not been previously described. The mainstay of treatment is a life-long Phe restricted diet together with supplementation of L-dopa and 5-hydroxy tryptophan (5-HT) and folinic acid. In Ireland, there is neurological comorbidity in our adult DHPR patients, although the overall outcome is satisfactory and one affected female has three healthy children. PMID- 26817293 TI - Paget's Disease of Bone: Progress Towards Remission and Prevention. AB - Paget's disease of bone is a focal disorder of bone remodelling leading to areas of enlarged weakened bone manifesting with chronic pain, bone deformity, and fracture. Predominantly a disease of older adults, its prevalence is strongly linked to European ancestry. Pre-disposing factors include exposure to viruses such as measles and mutations in the SQSTM1 gene. PDB is diagnosed on plain radiograph, the extent of disease is delineated by radionuclide bone imaging, the degree of activity is quantified biochemically, and it is treated with a nitrogen containing bisphosphonate, most effectively by a single intravenous infusion of zoledronate 5mg. Lifelong specialist follow-up is advocated because some patients require repeated infusions. Current clinical research is focusing on genetic factors in order to identify patients suitable for prevention. PMID- 26817294 TI - 'Life Saving Positioning' in Patients with Air Embolism. PMID- 26817295 TI - [Organ-sparing surgery in andrology]. AB - Penile and testicular tumors, especially those of the malignant nature, usually require radical excision, which alters the organ image, affects sexual and urinary functions, and consequently undermines the self-confidence and quality of life of the patient. Recent studies show that organ-sparing surgery can be an alternative to radical excision for superficial tumors and small masses. Penis sparing surgery (PSS) has been indicated for superficial penile cancer, such as Tis and T1a lesions, and testis-sparing surgery (TSS) is feasible for benign small bilateral or solitary testicular masses (TIN). Long-term follow-ups after PSS or TSS show that the patients may retain a satisfactory appearance of the organ as well as desirable sexual and reproductive functions. PMID- 26817296 TI - [In utero exposure to di-n-butyl phthalate induces testicular cell apoptosis and vacuolization in the pubertal male rat offspring]. AB - OBJECTIVE: To investigate the impact of in utero exposure to di-n-butyl phthalate (DBP) on the apoptosis of testicular cells in the pubertal male rat offspring. METHODS: Ten pregnant SD rats were randomly divided into a control and an experimental group to be treated intragastrically with olive oil (1 ml per day) and DBP (500 mg per kg of body weight per day) respectively between gestation days 12 and 19. At the pubertal age (postnatal day 45, PND 45), the testes of the male rat offspring were removed for observation of the cell structure under the transmission electron microscope and the development of different spermatogenetic cells by HE staining. The apoptosis of testicular cells was detected by the TUNEL method, the expressions of the apoptosis-regulating proteins Bcl-2, Bcl-XL, Bax and p53 were determined by immunohistochemistry and Western blot, and the data obtained were compared between the two groups by t-test. RESULTS: Transmission electron microscopy revealed increased apoptosis and vacuolization of testicular cells in the PND-45 rat offspring, HE staining showed markedly decreased numbers of different spermatogenetic cells, TUNEL manifested significantly increased apoptosis of testicular cells in the experimental group as compared with the control (12.00 +/- 5. 22 vs 3.17 +/- 1.47, P < 0.01), and immunohistochemistry and Western blot exhibited remarkably higher expressions of Bax and p53 in the former than in the latter group (P < 0.05). CONCLUSION: In utero exposure to DBP can increase the apoptosis of germ cells and Sertoli cells, induce the vacuolization of testicular cells, and significantly elevate the expressions of the apoptosis-promoting proteins Bax and p53 in the pubertal male rat offspring. PMID- 26817297 TI - [Nicotine- and tar-free cigarette smoke extract reduces the penile erectile function of rats]. AB - OBJECTIVE: To evaluate the impact of nicotine- and tar-free cigarette smoke extract (fCSE) on the serum testosterone (T) level and erectile function of male rats. METHODS: We randomized 30 male SD rats to three groups of equal number to receive subcutaneous injection of PBS (1.0 ml / 300 g body weight per day), fCSE (1.0 ml/300 g body weight per day), and reduced glutathione hormone (GSH, 200 mg per kg body weight per day) in addition to fCSE (fCSE + GSH), respectively, all for 8 weeks. Then we evaluated the erectile function of the rats by measuring the maximal intracavernous pressure (MICP), mean arterial pressure (MAP), ICP/MAP ratio, time of stimulation to MICP (Tmax), and cavernosal filling fate (CFR). We determined the serum T level, the activities of superoxide dismutase (SOD) , malondialdehyde (MDA), and nitric oxide synthase (NOS) in the cavernosal tissue, and also observed the morphological changes of the corpus cavernosum. RESULTS: Compared with the controls, the rats of the fCSE group showed obvious decreases in the levels of serum T ([5.37 +/- 1.43] vs [3.22 +/- 1.11] MUg/L), NOS ([2.90 +/- 0.27] vs [1.67 +/- 0.18] U/mg) , and SOD ([18.41 +/- 1.09] vs [13.36 +/- 1.18] U/mg prot) and erectile function-related indexes MICP ([85.92 +/- 6.36] vs [58.99 +/- 10.76] mmHg), MICP/MAP (0.86 +/- 0.09 vs [0.56 +/- 0.08]), and CFR (2.14 +/- 0.44 vs 0.89 +/- 0.44), but markedly increased Tmax ([29.90 +/- 5.78] vs [42.90 +/- 8.56]s), with a positive correlation between the serum T level and CFR (r = 0. 364, P < 0.05). Masson staining revealed a lower ratio of the corpus cavernosum smooth muscle tissue to collagen fiber in the fCSE group (0.27 +/- 0.04) than in the control (0.98 +/- 0.12). Compared with the fCSE group, the fCSE + GSH group exhibited significantly improved MICP ([58.99 +/- 10.76 ] vs [77.95 +/- 7.71] mmHg), MICP/MAP (0.56 +/- 0.08 vs 0.77 +/- 0.09), and CFR (0.89 +/- 0.44] vs 1.76 +/- 0.42) and shortened Tmax ([42.90 +/- 8.56 ] vs [32.10 +/- 5.84 ] s). The ratio of the corpus cavernosum smooth muscle tissue to collagen fiber was higher in the fCSE + GSH than in the fCSE group (0.77 +/- 0.09 vs 0.27 +/- 0.04) but still lower than in the control (0.98 +/- 0.12). CONCLUSION: Nicotine- and tar-free cigarette smoke extract reduces the serum T level and erectile function of rats, which is related to oxidative stress. Antioxidant therapy can improve erectile function but has a limited value for morphological protection of the penile tissue. PMID- 26817298 TI - [Benefit of network education to college students' knowledge about sexual and reproductive health in Ningbo city]. AB - OBJECTIVE: To investigate how network education can improve college students' knowledge on sexual and reproductive health in Ningbo city. METHODS: From December 2012 to June 2013, we conducted a questionnaire investigation among college students in Ningbo city about the effects of network education on their knowledge about sexual psychology, sexual physiology, sexual ethics, and reproductive health. RESULTS: A total of 7 362 college students accomplished the investigation, of whom 2 483 (42.1% males and 57.9% females) received network education, while the other 4 879 (24.1% males and 75.9% females) did not. Approximately 47.1% of the male and 28.0% of the female students acquired sexual and reproductive knowledge via network education. Reproductive health-related network education significantly enriched the students' knowledge about the reproductive system and sex, pubertal development, sexual physiology, conception and embryonic development, methods of contraception, sexual psychology, sexually transmitted diseases and their prevention, pregnancy care and eugenics, and environment- and occupation-related reproductive health (P < 0.01). It also remarkably improved their cognitive attitude towards reproductive health knowledge (P < 0.01). Those who received reproductive health-related network education showed a significantly higher rate of masturbation (P < 0.01) but markedly later time of the first masturbation (P < 0.01) than those who did not. CONCLUSION: Network education can enhance the effect of reproductive health education among college students and improve their sexual experience and health. PMID- 26817299 TI - [Impact of male reproductive tract infection on semen quality]. AB - OBJECTIVE: To investigate the association of male reproductive tract infection (RTI) with semen parameters and sperm DNA damage. METHODS: We classified 1 084 males attending the infertility clinic into an RTI group (n = 300) and a non-RTI control group (n = 784). According to the WHO standards, we obtained routine semen parameters, detected sperm morphology, and determined the sperm DNA fragmentation index (DFI) by sperm chromatin structure assay. RESULTS: There were statistically significant differences between the RTI and control groups in the semen volume ( [2.58 +/- 1.20] vs [3.00 +/- 2.10] ml), grade a + b sperm ([50.6 +/- 17.2] vs [53.2 +/- 15.8]%), grade d sperm ( [39. 8 +/- 17.8] vs [36.5 +/- 16.2]%), and total sperm count ([218.5 +/- 185.0 ] vs [278.5 +/- 375.5 ] x 10(6)/ejaculate) (all P < 0.05), but not in the males' age, sperm concentration or pH value (P > 0.05). The percentage of morphologically normal sperm was significantly lower ([3.46 +/- 2.90] vs [4.61 +/- 3.60%, P < 0.05) but the DFI was markedly higher in the RTI group than in the control ([19.4 +/- 11.4] vs [15.2 +/- 8.8]% , P < 0.01). The percentage of the cases with DFI > 30% was remarkably higher (13.0 vs 5.74% ) while that of the cases with DFI < 10% dramatically lower in the former than in the latter (16.0 vs 28.0%). The level of seminal plasma elastase was correlated negatively to sperm concentration, sperm count, and the percentage of morphologically normal sperm (P < 0.05) but positively to DFI and grade d sperm (P < 0.05 or P < 0.01). CONCLUSION: Male reproductive tract infection not only affects semen parameters and sperm morphology but also causes serious sperm DNA damage. PMID- 26817300 TI - [Correlations of 24 biochemical markers in seminal plasma with routine semen parameters]. AB - OBJECTIVE: To investigate the correlations of 24 biochemical markers in the seminal plasma with routine semen parameters. METHODS: According to the WHO5 standards, we analyzed the routine semen parameters of 66 subfertile men, including the semen volume, sperm concentration, total sperm count, sperm motility, and the percentage of progressively motile sperm (PR). Based on the calibration and quality control measures and using an automatic biochemistry analyzer or electrolyte analyzer, we detected 24 biochemical markers in the seminal plasma of the patients, including total protein (TP), albumin (Alb), globulin (Glb), uric acid (UA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), creatine kinase (CK), alpha hydroxybutyrate dehydrogenase (alphaHBDH), adenosine deaminase (ADA), glucose (Glu), triglyeride (TG), total cholesterol (TC), urea nitrogen (UN), creatinine (Cr), high-sensitive C-reactive protein (hsCRP), K+, Na+, Cl- , Ca, Mg, and phosphorus (P). Then we analyzed the correlations of the 24 biochemical markers with routine semen parameters. RESULTS: The levels of the TP, Alb, and Glb proteins in the seminal plasma were positively correlated with sperm concentration, so was that of Alb with the total sperm count, and the AST and LDH activities with sperm concentration and total sperm count. The AKP activity in the seminal plasma was correlated negatively with the semen volume, but positively with sperm motility. The alphaHBDH activity exhibited a positive correlation with both sperm concentration and total sperm count, with a coefficient of correlation (r) above 0.7. The UN level was correlated negatively with the semen volume, so was the Cr level with the semen volume, sperm concentration, and total sperm count, and the Glu level with sperm concentration and total sperm count. The TG level was correlated positively with the semen volume, but negatively with sperm motility. The levels of seminal plasma ALT, GGT, ADA, UA, TC, CK, and hsCRP showed no correlation with the above-mentioned semen parameters. None of the seminal plasma K+, Na+, Ca, Mg, and P levels was found correlated with semen parameters except the Cl- level, which was negatively correlated with the semen volume. CONCLUSION: Many biochemical markers in the seminal plasma are closely related to routine semen parameters, indicating that these biochemical components may play roles in spermatogenesis, sperm maturation, and physiological metabolism. PMID- 26817301 TI - [Strategies of sperm collection from men with temporary penile erectile dysfunction on the day of oocyte retrieval and the outcomes of IVF-ET]. AB - OBJECTIVE: To search for the optimal strategies for sperm collection from the patient with temporary penile erectile dysfunction (ED) on the day of oocyte pick up ( OPU) in in vitro fertilization embryo transfer (IVF-ET). METHODS: We retrospectively analyzed 93 cases of temporary ED on the OPU day of IVF-ET from January 2011 to May 2014, with fresh semen for 45 cases (group A), cryopreserved sperm before oocyte retrieval for 30 cases (group B), and frozen oocytes for 18 cases (group C). Group A was again subdivided into A1 (n = 18) and A2 n = 27) , the former intervened with oral sildenafil while the latter left untreated. We compared the rates of fertilization, high-quality embryo, and pregnancy among different groups. RESULTS: No statistically significant differences were found among groups A, B and C in the age of the males and females, duration of infertility, numbers of obtained and mature oocytes, and rates of cleavage, or in the percentages of normal fertilization (80.78% vs 80.43% vs 84.77%), high quality embryo (53.27% vs 52.97% vs 47.69%) and pregnancy (60.00% vs 56.77% vs 44.44%) (all P > 0.05). The rate of 3PN was markedly lower in group C (0.63%) than in A (9. 61%) and B (4.34%) (P < 0.05). There were no significant differences between groups A1 and A2 in the age of the males and females, duration of infertility, numbers of obtained and mature oocytes, and the rates of fertilization, cleavage, high-quality embryo, and pregnancy (all P > 0.05). CONCLUSION: On the OPU day of IVF-ET, oral sildenafil can help temporary ED men to achieve penile erection and ejaculation without affecting the outcomes of assisted reproduction. Cryopreserved sperm can be used in case of predicted temporary ED and frozen oocytes can also be employed if sperm retrieval fails. However, to avoid puncture injury to the epididymis or testis, fresh semen should be the first choice. PMID- 26817302 TI - [Efficacy and safety of Saw Palmetto Extract Capsules in the treatment of benign prostatic hyperplasia]. AB - OBJECTIVE: To assess the efficacy and safety of Saw Palmetto Extract Capsules in the treatment of benign prostatic hyperplasia (BPH). METHODS: We conducted a multi-centered open clinical study on 165 BPH patients treated with Saw Palmetto Extract Capsules at a dose of 160 mg qd for 12 weeks. At the baseline and after 6 and 12 weeks of medication, we compared the International Prostate Symptom Scores (IPSS), prostate volume, postvoid residual urine volume, urinary flow rate, quality of life scores (QOL), and adverse events between the two groups of patients. RESULTS: Compared with the baseline, both IPSS and QOL were improved after 6 weeks of medication, and at 12 weeks, significant improvement was found in IPSS, QOL, urinary flow rate, and postvoid residual urine. Mild stomachache occurred in 1 case, which necessitated no treatment. CONCLUSION: Saw Palmetto Extract Capsules were safe and effective for the treatment of BPH. PMID- 26817303 TI - [Human papillomavirus genotypes in male patients attending the STD clinic in Zhenjiang area]. AB - OBJECTIVE: To investigate the status of human papillomavirus ( HPV) infection and its genotypes in male patients in Zhenjiang area. METHODS: Using PCR and reverse dot blot hybridization, we determined the genotypes of HPV DNA in 245 male patients at our Clinic of Dermatology and STD. RESULTS: The total rate of HPV infection was 43.67% (107/245), and 18 subtypes were detected. Among the 107 HPV positive cases, low-risk, high-risk, and combined high- and low-risk infections accounted for 39.25% (42/107), 38.32% (41/107), and 22.43% (24/107), respectively. The most notable low-risk HPV types were HPV6 and HPV11, and the most notable high-risk HPV types were HPV16, HPV52, and HPV58. The rates of single infection and multi-infection were 53.27% (57/107) and 46.73% (50/107), respectively. One case had the most types, infected with 8 genotypes. No statistically significant differences were observed in the total rate of HPV infection among different age groups (Chi2 = 7.999, P > 0.05). CONCLUSION: The dominant subtypes of HPV infection in male patients in Zhenjiang area were HPV6, HPV11, and HPV16. The most common subtypes were HPV6 and HPV11 in low-risk infection, and HPV16, HPV52, and HPV58 in high-risk infection. PMID- 26817304 TI - [Robot-assisted laparoscopic prostatectomy versus laparoscopic radical prostatectomy for the management of prostate cancer]. AB - OBJECTIVE: To compare robot-assisted laparoscopic radical prostatectomy (RALRP) with laparoscopic radical prostatectomy (LRP) in the treatment of prostate cancer and investigate the clinical application value of RLRP. METHODS: We retrospectively analyzed 70 cases of prostate cancer treated by RALRP and another 32 cases treated by LRP. We compared the operation time, intraoperative blood loss and transfusion, catheter-indwelling time, postoperative hospital stay, incisal margin positive rate, biochemical recurrence, and normal postoperative urinary continence and penile erectile function between the two groups of patients. RESULTS: All the operations were successfully accomplished. RALRP exhibited a significant superiority over LRP in intraoperative blood loss and transfusion, catheter-indwelling time, and postoperative hospital stay, urinary continence and erectile function (P < 0.05). CONCLUSION: Robot-assisted laparoscopic radical prostatectomy, with its advantages of few postoperative complications and well-preserved urinary continence and penile erectile function, is an effective, safe and minimally invasive surgical option for prostate cancer. PMID- 26817305 TI - [Effects of the combination of musk and olibanum on the expressions of tight junction proteins in the prostate epithelial cells of rats]. AB - OBJECTIVE: To investigate the effects of the combination of musk and olibanum on the tight junction protein expressions in prostatic epithelial cells of normal and chronic prostatitis (CP) rats. METHODS: Eighty male SD rats were randomly divided into 8 groups of equal number: normal control, normal musk, normal olibanum, normal musk + olibanum, CP model control, CP model musk, CP model olibanum, and CP model musk + olibanum. At 60 days after modeling, the rats in the control, musk, olibanum, and musk + olibanum groups were treated intragastrically with normal saline, musk (0.021 g per kg body weight per day), olibanum (1.05 g per kg body weight per day), or musk + olibanum respectively, all for 3 days. Then, all the rats were sacrificed and their prostate tissues harvested for detection of the expressions of the tight junction proteins Claudin 1, Claudin-3, Occludin, and ZO-1 in the prostatic epithelial cells by immunohistochemical staining. RESULTS: In the CP models, only the expression of Claudin-1 was significantly increased. In the normal rats, the expression of Claudin-1 was remarkably upregulated after treated with musk (824.6 +/- 393.3, P < 0.05), olibanum (982.0 +/- 334.0, P < 0.05), and musk + olibanum (1088.1 +/- 640.2, P < 0.01); that of Claudin-3 was elevated markedly by olibanum (1 009.5 +/ 243.6, P < 0.05) and insignificantly by musk (597.5 +/- 80.7), but the increasing effect of olibanum was reduced by musk + olibanum (678.4 +/- 255.1). No statistically significant differences were found in the expression of Occludin among the rats treated with musk (693.0 +/- 424.8), olibanum (732.1 +/- 302.0), and musk + olibanum (560.2 +/- 202.3), or in that of ZO-1 in the animals treated with musk (290.0 +/- 166.8) and olibanum (419.7 +/- 108.1), but the latter was markedly decreased in the musk + olibanum group (197.7 +/- 98.2, P < 0.05). In the CP rat models, both the expressions of Claudin-1 (823.0 +/- 100.1, P < 0.01) and Occludin (1160.0 +/- 32.2, P < 0.05) were significantly increased. The expression of Claudin-1 was remarkably down-regulated by musk (764.9 +/- 179.0), olibanum (468.4 +/- 220.4), and musk + olibanum (335.1 +/- 204.0) (all P < 0.05), but that of Claudin-3 up-regulated by musk (744.6 +/- 94.5) and olibanum (700.1 +/- 223.7) (both P < 0.05). The expression of Occludin was reduced by musk (615.0 +/- 221.0), olibanum (749.6 +/- 321.7), and musk + olibanum (505.8 +/- 523.7), while that of ZO-1 increased by olibaum (443.2 +/- 44.9) and decreased by musk + olibanum (213.5 +/- 24.9, P < 0.05). CONCLUSION: In physiological and pathological conditions, the combination of musk and olibanum acts on the expressions of tight junction proteins in prostate epithelial cells in a selective and dual-targeting manner, promoting their permeability by down regulating the expression of ZO-1 and maintaining their structural stability by regulating the expressions of Claudin-1, Claudin-3, and Occludin. PMID- 26817306 TI - [Sertraline hydrochloride combined with four-spot caressing for primary premature ejaculation]. AB - OBJECTIVE: To investigate the clinical effectiveness of sertraline hydrochloride combined with four-spot caress in the treatment of primary premature ejaculation (PE). METHODS: We randomly assigned 90 primary PE patients to three groups of equal number. The patients in group A (aged [28.1 +/- 5.2] yr and with a disease course of [3.1 +/- 1.9] yr) were treated with oral sertraline hydrochloride at 50 mg qd, those in B (aged [27.8 +/- 4.1] yr and with a disease course of [3.2 +/- 2.0] yr) by four-spot caressing (caressing the tongue, breasts, and vulva prior to intercourse), and those in C (aged [27.1 +/- 4.7] yr and with a disease course of [3.1 +/- 2.0] yr) by the combination of oral sertraline hydrochloride and four spot caressing, all for 12 weeks. Before and after 4, 8, and 12 weeks of treatment, we obtained the intravaginal ejaculatory latency time (IELT) and Chinese Index of Sexual Function for Premature Ejaculation-5 (CIPE-5) scores and compared them among the three groups of patients. RESULTS: The IELT was dramatically prolonged in groups A, B, and C after 4 weeks ([1.08 +/- 0.29], [0.93 +/- 0.28] and [1.21 +/- 0.27] min), 8 weeks ([1.43 +/- 0.30], [1.20 +/- 0.33] and [1.72 +/- 0.42] min) and 12 weeks of treatment ([2.12 +/- 0.63], [1.90 +/- 0.65] and [2.67 +/- 0.82] min) as compared with the baseline ([0.63 ?0.14] , [0.60 ?0.14] and [0.62 ?0.11] min) (P < 0.05), even longer in group C than in A and B (P < 0.05). The CIPE-5 scores were markedly improved in groups A, B and C after 4 weeks ([15.17 +/- 1.74], [14.57 +/- 1.94] and [15.60 +/- 1.63] min), 8 weeks ([17.13 +/- 1.63], [16.37 +/- 1.97] and [18.00 +/- 1.05] min) and 12 weeks of intervention ([18.93 +/- 1.57], [18.53 +/- 1.67] and [20.00 +/- 1.46] min ) as compared with the baseline ([12.57 +/- 2.05], [13.20 +/- 2.51] and [13.07 +/- 2.01] min) (P < 0.05), even higher in group C than in A and B (P < 0.05). CONCLUSION: Sertraline hydrochloride combined with four-spot caressing, with its definite efficacy and rare adverse reactions, deserves wide clinical application in the treatment of primary PE. PMID- 26817307 TI - [Treatment of castration-resistant prostate cancer: Evidence-based clinical practice]. AB - OBJECTIVE: To introduce the framework of evidence-based practice with a case of castration-resistant prostate cancer (CRPC) as an example. METHODS: A clinical question was formulated according the clinical scenario. A systematic search was conducted for the published literature in the databases of PubMed, EMBASE, Cochrane Library, Clinical Trial Registries, and Web of Knowledge up to Dec 2014. The identified literature was reviewed for quality appraisal before the evidence was applied to clinical practice. RESULTS: The treatment was effective and the patient achieved disease remission. CONCLUSION: Evidence-based practice should be integrated with clinical scenario, current evidence, and patients' willingness, and follow a systematic framework. PMID- 26817308 TI - [Action mechanisms of prolactin and its receptors on penile erection and ejaculation]. AB - Prolactin is a polypeptide hormone which mainly acts on the reproductive system and plays an important role in penile erection and ejaculation. Prolactin receptors have a variety of short forms apart from the classic long form, which are widely expressed in male reproductive glands. High levels of prolactin can induce erectile dysfunction and results in secondary male infertility, which are mainly associated with the inhibition of dopaminergic activity, reduction of the testosterone level, and contraction of the cavernous smooth muscle. Moreover, low levels of prolactin can result in ejaculatory dysfunction. This article updates the views on the expressions of prolactin receptors in the male reproductive system, the effects of prolactin on penile erection and ejaculation, and its action mechanisms. PMID- 26817309 TI - [Ouabain and asthenospermia]. AB - Asthenospermia accounts for about 30% of the causes of male infertility. Currently, most drugs for asthenospermia lack specificity and desirable therapeutic efficiency. An insight into the pathogenesis of asthenospermia is important for the development of specific therapies for this disease. The protein Na+/K(+)- ATPase alpha4 isoform (NKA4) presents in both mature testis tissue and the sperm tail, the absence or reduced activity of which may significantly decrease sperm motility. Ouabain is a natural inhibitor of NKA4, suppressing its activity by specifically binding the ouabain site in it. The hypothalamus and adrenal cortex excrete an ouabain-like steroid hormone called endogenous ouabain (EO), which may be associated with the pathogenesis of asthenospermia by inhibiting the activity of NKA4, affecting Na+/H+ exchange, Na+/Ca2+ exchange and sperm cell membrane potential, and eventually reducing sperm motility. PMID- 26817310 TI - [Protamine gene polymorphisms and male infertility]. AB - Protamine (PRM) is one of the most abundant arginine-rich nucleoproteins in sperm and plays an important role in spermatogenesis. In the late stage of spermatogenesis, the replacement of PRM by histone prompts the closer combination between the nuclear matrix of sperm and nucleoprotein in order for high enrichment and condensation of nuclear chromatin in addition to preventing the sperm genome from mutation induced by internal and external factors. With the development of DNA sequencing techniques, researches on the association between PRM polymorphisms and male fertility are surfacing as a hot field. Many studies show that rs2301365 polymorphism is a risk factor for male infertility and increases the risk of male infertility by 27 - 66%, that rs737008 polymorphism of PRM1 and rs1646022 polymorphism of PRM2 are protective factors against Asian infertility, and that the ratio of PRM1 to PRM2 is intensively associated with male infertility. This review presents an update on the association between PRM gene polymorphisms and male infertility. PMID- 26817311 TI - [Estimation of fetal middle cerebral artery peak systolic velocity at 18-39 weeks of gestation in Polish population]. AB - OBJECTIVES: The aim of this paper was to establish normal values of fetal middle cerebral artery peak systolic velocity (MCA-PSV) between 18-39 weeks' gestation in the Polish population and to compare the results with values published by other authors, for different populations seeking the discrepancies between them. MATERIAL AND METHODS: 280 healthy pregnant women from the Polish population underwent ultrasound examination. The cross-sectional data were obtained based on the measurements of fetal middle cerebral artery peak systolic velocity A chart of normal MCA-PSV values as a function of the gestational age was constructed. RESULTS: Normal ranges for MCA-PSV in the Polish population were established. The results were compared with values published by other authors, for different populations. CONCLUSIONS: The use of MCA-PSV measurements has proven itself to be a reliable method in diagnosis of fetal anemia. Differences in normal values of MCA-PSV in the Polish population compared with other nations have been observed. PMID- 26817312 TI - [The impact of metabolic control on uteroplacental circulation parameters in pregnancies complicated by gestational hypertension and/or preeclampsia in pregnant women with pregestational diabetes]. AB - OBJECTIVES: The aim of the study was to evaluated the impact of metabolic control in pregnant women with PGDM on uteroplacental circulation parameters during pregnancy. MATERIAL AND METHODS: The study group included 141 pregnant women divided into 3 subgroups: PE + GH group (n = 16)--woman suffering from PGDM, with superimposed PE or GH, the PGDM group (n = 84)--women suffering from PGDM without hypertension, and the control group--41 healthy women in uncomplicated pregnancy. All participants were monitored for metabolic control and uteroplacental circulation parameters during pregnancy. The survey was completed after the data from the perinatal period were collected. RESULTS: The differences between the uterine artery pulsatility index (Pi UtA) in the first trimester of pregnancy expressed as a multiple of the median (MoM), were not statistically significant between the groups (p >= 0.42). Also, no statistically significant differences were observed between the groups Pi UtA in the second (p >= 0.33) and third trimester of pregnancy (p = 1.0). The rate of fetal growth was comparable in all groups. Infant birth weight percentile in the study groups did not differ statistically (p >= 0.15). CONCLUSIONS: Tight metabolic control during pregnancy in women suffering from PGDM allows to obtain blood flow in the uteroplacental circulation which is comparable to their healthy pregnant peers. PMID- 26817313 TI - [Evaluation of the correlation between IL-1beta, IL-8, IFN-gamma cytokine concentration in cervico-vaginal fluid and the risk of preterm delivery]. AB - OBJECTIVES: The aim of the study was to evaluate IL-1beta, II-8, IFN-gamma cytokine concentrations in cervico-vaginal fluid in patients with threatening preterm delivery. MATERIAL AND METHODS: The study group included 84 patients between 27 and 34 weeks of pregnancy admitted with symptoms of threatened preterm delivery. The cervico-vaginal fluid was taken from each patient qualified for the study and IL-1beta, II-8, IFN-gamma concentration was analyzed by enzyme-linked immunosorbent assay (ELISA). The following factors were analyzed: maternal age and parity gestational age at admission for the examination and at delivery, sex of the newborn, Apgar evaluation at 1 and 5 minutes of life, umbilical blood pH, history of miscarriage or preterm delivery pre-pregnancy body mass index, and smoking. Their influence on the concentration of biochemical markers tested in patients at risk of preterm delivery was investigated. RESULTS: In the study group, patients who delivered preterm had significantly higher concentrations of IL-1beta and II-8 as compared to patients who delivered at term. Patients who delivered preterm more often had a history of a miscarriage and their newborns had lower birth weight, lower Apgar score, and lower pH of the umbilical blood. CONCLUSION: As far as factors significantly influencing cytokine concentrations are concerned, the level of IL-1beta and II-8 concentration is an independent predictor of preterm delivery in patients with threatened preterm labor. In the study group, the IFN-gamma concentration did not significantly diversify patients who delivered preterm and at term. PMID- 26817314 TI - The role of cytokines in first trimester pregnancy losses with fetal chromosomal anomaly. AB - OBJECTIVES: The contribution of local inflammation to the pathophysiology of abnormal choromosomally miscarriages remains unclear The objective of this study was to investigate the inflammatory response at the maternofetal interface of women presenting with first trimester miscarriage with abnormal choromosomally MATERIAL AND METHODS: Level of TNF-alpha , IL-6 ve IL-17 were asseyed using immunohistochemistry technique at decidual and placental bed biopsy samples from 23 women with elective termination of pregnancy 21 euploid and 18 aneuploid missed miscarriages. Immunostainig for TNF-alpha, IL-6 ve IL-17 has been evaluated semi-quantitatively by 'quickscore' method. RESULTS: We found that the intensity of TNF-alpha staining was high in the miscarriage group, and this has been found in previous studies. Unlike some previous studies, the intensity of IL 6 staining was higher in the miscarriage groups only in decidual glandular epithelium. The intensity of IL-6 staining was found to be higher in the miscarriage group with chromosome anomaly than in the miscarriage group without chromosome anomaly. There was no significant difference in IL-17 levels between any of the groups. CONCLUSIONS: Cytokines are considered to play an important role in the maintenance of pregnancy but the exact mechanism between them and the mutual regulation relationship were not been fully understood, which need our further study. PMID- 26817315 TI - [Evaluation of the expression of selected pro- and anti-apoptotic factors in syncytiotrophoblasts of human placenta and changes observed after vitamin supplementation]. AB - AIM: The main aim of the study was to estimate expression of Bcl-2 and Bax proteins in syncytiotrophoblast in placenta obtained from pregnancies complicated by hypertension and to compare results with group supplemented by antioxidants. MATERIAL AND METHOD: The study was performed in High Risk Department of Medical University Lodz. 3 groups of pregnant women were compared: I-pregnancy complicated by hypertension, II pregnancy complicated by hypertension treated by oral administration of antioxidants--vitamin C and vitamin E.III-rd group consisted of healthy women. After delivery incision from central part of placenta was taken on obtained slides due to immunohistochemical reactions the character intensity surface affected by reaction and expression of two proteins involved into process of apoptosis was measured- anti-apoptotic Bcl-2 and pro-apoptotic Bax. In every slide ten of random choosen fields were evaluated in 200x zoom using semi-quantative method. RESULTS: Highest value of Bcl-2 character was found in I-st group, the lowest in III-rd group- healthy women. The lowest intensity surface affected and expression of the reaction was found in II group- treated by antioxidants. The highest value of Bax reaction character and intensity was found in III group comparing to others. The lowest mean surface of syncytiotrophoblast affected by Bax reaction was found in II group. In III-rd group expression of reaction was higher than in both other groups. CONCLUSIONS: In the base of Bcl-2 reaction in syncytiotrophoblast no influence of antioxidants supplementation on apoptosis process that occurs by this path was found. Antioxidants supplementation decrease Bax activity in syncytiotrophoblast, that suggests restriction of apoptosis process despite of changes connected to hypertension. PMID- 26817316 TI - Cardiometabolic risk in patients with polycystic ovary syndrome. AB - OBJECTIVES: Polycystic ovary syndrome (PCOS) is a common endocrinopathy in premenopausal women, associated with risk of metabolic syndrome and cardiovascular disease (CVD). CVD risk evaluation is recommended for PCOS patients. This study aimed to evaluate the risk of CVD in PCOS patients and to identify the best predictors for metabolic and cardiovascular disturbances. MATERIAL AND METHODS: The study included 169 PCOS patients and 110 healthy women in reproductive age. We estimated cardiovascular risk according to American Heart Association and Androgen Excess-PCOS Society criteria that classified patients as metabolically unhealthy (MU) or metabolically healthy (MH). RESULTS: The PCOS group had significantly higher body mass index (BMI), waist circumference, and waist-to-hip ratio (P < 0.000001). Metabolic syndrome was only defined among PCOS patients (8.9%). No obesity was observed in the control group. Waist circumference >= 80 cm was presented in 44% of PCOS patients in comparison to 14.5% of control participants (P < 0.000001). There was a significant tendency for higher fasting insulin levels in the PCOS population (P < 0.00001). Surprisingly the PCOS-MH group had the highest high-density lipoprotein (HDL) levels. ROC curves were used to indicate parameters diagnosing metabolically unhealthy women and revealed that WC, BMI and HC seem to be the strongest predictors of metabolic disturbances in PCOS but in the healthy population in reproductive age biochemical findings such as low HDL or increased fasting glycemia presented stronger predictive value than patients' anthropometric features. CONCLUSIONS: Physicians need to remember to adopt different diagnostic approach while seeking metabolic complications in these different groups of women. PMID- 26817317 TI - [Treatment costs of malignant cervical cancer in Poland in 2011-2012--the case of Silesian Voivodeship]. AB - OBJECTIVES: As far as health economics is concerned, it is hard to determine the only useful tool which would disclose the actual costs associated with cancer. We analyzed hospitalization costs, which create the highest rate among all malignant cervical cancer-related medical costs. The main aim of the study was to evaluate the real costs of medical treatment in the case of patients diagnosed with cervical cancer based on the group with the primary and coexisting diagnoses. MATERIAL AND METHODS: The analyzed data from 2011-2012 were obtained from the Silesian branch of the National Health Fund, which financed medical expenses due to the diagnosis of cancer in health facilities which have the agreement for such treatment. RESULTS: A total of 4 540 hospitalization-related health benefits were realized, with the final total cost was PLN 8 766 547, in the presented group of 2261 patients. The most popular procedures in patients with the diagnosis from the C53 group, included chemotherapy together with oncological hospitalization (over 62%). The vast majority of the realized procedures were treatments of the reproductive system (38%) and teleradiotherapy (about 31%). CONCLUSIONS: Lack of efficient procedures of data collection for cancer advancement hinders the economic analyses, which should constitute the foundation for the discussion about cost effectiveness of selected procedures. Adequate methods for the monitoring of direct and indirect costs associated with cervical cancer treatment ought to be created. PMID- 26817318 TI - [The role of miRNA in endometrial cancer in the context of miRNA 205]. AB - MiRNAs are small, non-coding molecules of ribonucleic acids of approximately 22 bp length, which serve as regulators of gene expression and protein translation due to interference with messenger RNA (mRNA). MiRNAs, which take part in the regulation of cell cycle and apoptosis, may be associated with carcinogenesis. Aberrant expression of miRNAs in endometrial cancer might contribute to the endometrial cancer initiation or progression, as well as metastasis formation, and may influence cancer invasiveness. Specific-miRNAs expressed in endometrial cancer tissues may serve as diagnostic markers of the disease, prognostic biomarkers, or play an important part in oncological therapy We aimed to describe the role of miRNAs in endometrial cancer with special consideration of miRNA 205. PMID- 26817319 TI - [Cleft lip and palate--risk factors, prenatal diagnosis, and health consequences]. AB - Cleft lip and/or palate is a diverse and important group of congenital malformations. The incidence is estimated at 1 in 600-1000 births worldwide. In Poland, there are 2-3 cases noted per 1000 live births. The process of the formation of a correctly developed lip and palate can be impaired by a variety of factors, including the extremely important role of the interaction between genetic and environmental factors (smoking, alcohol consumption, medication use, and exposure to certain chemicals). This study focuses on environmental risk factors, prenatal diagnosis, and health consequences of cleft lip and palate. PMID- 26817320 TI - [Retroperitoneal fibrosis--case report and literature review]. AB - The purpose of the study was to present the symptoms, diagnostic methods, and treatment in retroperitoneal fibrosis (RPF). We present a case of a 53-year-old woman admitted to the hospital due to low back and abdominal pain complaints lasting a year. Ultrasonography revealed a myoma located along the right bank of the uterus. Six months after myoma enucleation, the patient underwent relaparotomy due to intensifying pain. The surgery revealed the presence of highly vascularized tissue; ureteral structure and topography of the right retroperitoneal were abolished, and anatomical borders were obliterated. Ureteral right catheter was placed, retroperitoneal adhesions were released and tissue fragments were collected from the retroperitoneal space for intraoperative histopathological examination. The result of histopathological examination indicated the presence of eosinophiia, adult fibroblasts proliferation, lymphocyte and plasmocyte infiltration, which confirmed the diagnosis of RPF. Corticosteroid therapy, which was applied during the postoperative period, minimized the pain. PMID- 26817321 TI - [Ovarian cancer during pregnancy--presentation of three cases and current diagnostic and treatment algorithms]. AB - INTRODUCTION: Malignant tumors are rarely diagnosed during pregnancy and their incidence ranges from 2.4% to 5.7%. Ovarian cancer is ranked fifth among all cancer types and second among all genital cancers diagnosed during pregnancy The course of the disease is asymptomatic in most cases and the initial diagnose is typically made during a routine ultrasound examination. Management of ovarian cancer during pregnancy presents a considerable challenge due to the absence of clear standards of treatment. OBJECTIVES: We present three clinical cases of patients suffering from ovarian cancer diagnosed during pregnancy a review of the literature, as well as possible therapeutic options. RESULTS: Three different clinical scenarios in patients with ovarian cancer diagnosed during pregnancy have been presented. In addition, we reviewed current diagnostic and therapeutic algorithms for patients with ovarian cancer and co-existing pregnancy. CONCLUSIONS: Approximately 5% of ovarian tumors diagnosed in pregnancy are malignant. There are no treatment standards for ovarian cancer diagnosed during pregnancy. Surgical treatment and the subsequent chemotherapy in the 2nd trimester of pregnancy appear to be safe for both, the mother and the child. However, the potential risks and benefits associated with the treatment have to be thoroughly analyzed on a case-by-case basis, to establish optimal diagnostic and treatment algorithms. PMID- 26817322 TI - [The chairman of the Cracow Medical Society Prof. Igor Goscinski MD, PhD--Jubilee of the 85th birthday]. PMID- 26817323 TI - [Professor Igor Goscinski w Juventus Christiana]. PMID- 26817324 TI - [Thanks for Professor Igor Goscinskiego]. PMID- 26817325 TI - Evening not morning plasma cortisol level is higher in women with polycystic ovary syndrome. AB - INTRODUCTION: The aim of our study was to assess the morning and evening cortisol plasma levels in women with polycystic ovary syndrome (PCOS). MATERIAL AND METHOD: 95 patients gave their informed consent to participate in the study and were divided into 2 groups. Group A consisted of 40 PCOS patients and group B consisted of 55 women without features of PCOS. Between day 5 and 8 of the menstrual cycle, morning (7 am), fasting blood samples were taken for the assessment of luteinizng hormone (LH), follicle stimulating hormone (FSH), estradiol, cortisol, prolactin, thyreotropin (TSH), testosterone and dehydroepeiandrosterone (DHEAS). Evening (5 pm) blood samples were also taken for the evaluation of plasma cortisol level RESULTS: There were no differences in mean age, body mass index (BMI), FSH, SHBG, PRL, estradiol and TSH levels between group A and group B. Mean plasma LH level was higher in group A compared to group B (10.7 +/- 6.8 IU/l vs 6.6 +/- 4.5 LU/l, p < 0.02). Mean plasma testosterone and DHEAS levels were also higher in PCOS patients (3.8 +/- 0.6 nmol/l vs 1.63 +/- 0.6 nmol/l; 427.7 +/- 162.9 vs 236.6 +/- 97.8 respectively, p < 0.001). Mean evening plasma cortisol level was higher in PCOS patients (11.8 +/- 4.1 ug/dl vs 4.7 +/- 1.3 ug/dl, p < 0.02). Mean morning plasma cortisol levels did not differ between groups. CONCLUSION: PCOS women showed the increased evening plasma cortisol level with impacted diurnal secretion rate. PMID- 26817326 TI - Orthodontic treatment in oncological patients. AB - The progress in oncological treatment has led to the current increase of childhood cancer survival rate to 80%. That is why orthodontists more and more frequently consult patients who had completed a successful anti-cancer therapy in childhood. Oncological treatments such as chemotherapy, radiotherapy or supportive immunosuppressive therapy cause numerous side effects in growing patients, connected i.a. with growth, the development of teeth or the viscerocranium. This is a special group of patients that needs an optimised plan of orthodontic treatment and often has to accept a compromise result. The purpose of the current work is to discuss the results of orthodontic treatment in patients after an anti-cancer therapy. Time of treatment was 12,5 months. In 6 patients (from 40 undergoing orthodontic therapy) we haven't reached a normocclusion, in 9 patients we should have stopped the therapy because of the recurrence. In 11 patients we found mucosa inflammation and in 1 patient the therapy stopped before the end because of very low oral hygiene level. Bearing in mind the limited number of original works on the above topic in Polish medical literature, the study has been carried out in order to make Polish orthodontists more acquainted with the topic and the standards of dealing with an oncological patient. PMID- 26817327 TI - [Evaluation of heart rate and blood pressure variability in Parkinson's disease patients after bilateral subthalamic deep brain stimulation]. AB - INTRODUCTION: Autonomic dysfunctions are the most common non-motor symptoms of Parkinson's disease (PD) and often precede the motor symptoms of the disease. Autonomic dysfunction may be a dominant symptom of the advanced stages of PD as well as a major cause of patient disability. Despite the wide use of neurostimulation in clinical practice, the effect of deep brain stimulation of subthalamic nucleus (STN DBS) on autonomic symptoms of PD still remains only partially understood. The aim of the study is evaluation of heart rate variability (HRV) and blood pressure variability (BPV) in patients with PD before STN DBS and following bilateral STN DBS. MATERIAL AND METHODS: The study included 25 subjects aged between 31 and 71 years, diagnosed with the idiopathic PD and selected for treatment with STN DBS. All the patients were in advanced stages of PD, disease duration ranged from 5 to 22 years. The patients enrolled into this study underwent STN DBS. Neurological examination including assessment of the severity of parkinsonism according to UPDRS scale, a psychological examination and an electrophysiological examination of autonomic disturbances based on heart rate and blood pressure variability were conducted on all patients two weeks before and three months after STN DBS. RESULTS: After STN DBS an improvement in terms of the analyzed parts of the UPDRS has been shown. The improvement of motor disorders assessed by III part UPDRS during the "off" medication/stimulation "on" was 67.8%. Orthostatic hypotension before the STN DBS procedure was observed in 56% of patients and after STN DBS in 53% of them. Before STN DBS the imbalance of the sympathetic--parasympathetic components with the predominance of the sympathetic based on HRV parameters--the ratio LF/HF-RRI (2.5) and a higher rate of LFnu (61.3%) than HFnu (38.6%) has been shown. Three months post STN DBS an increase parameters of spectral analysis of HRV in the low frequency LF-RRI, and high-frequency HF-RRI and the total power spectrum PSD-RRI was observed. After STN DBS an increase of parameters of spectral analysis of systolic BPV, very low frequency VLF-sBP, low frequency LF-sBP and total power spectrum PSD-sBP was noted. CONCLUSIONS: Results of the study suggest that STN DBS is an effective treatment method of both motor symptoms and autonomic dysfunctions. The disturbances of HRV and BPV before and after STN DBS indicate the increase of autonomic system activity with sympathetic dominance. PMID- 26817328 TI - [Superficial mycoses--analysis of mycological examinations from Mycology Laboratory in Krakow in years 2010-2014]. AB - INTRODUCTION: Superficial fungal infections are a major epidemiological issue with increasing prevalence. Mycological examination is crucial for proper diagnosis. The aim of this study was to determine the epidemiological and etiological factors of superficial fungal infections in Malopolska and the incidence of superficial fungal infections in relation to sex and age. MATERIALS AND METHODS: We analyzed 4608 results of mycological examinations taken from patients in 2010-2014 in Mycology Laboratory in Krakow. Materials were collected from affected areas: nails, skin of feet and hands, the smooth skin and hairy skin. The material was examined directly and cultured. RESULTS: Among 4608 collected materials culture was positive in 1765 cases. Dermatophytes were the most common isolates (865; 49%), followed by yeasts (702; 39.8%) and non dermatophytic molds (161; 9.1%). There were 37 (2.1%) co-infections. Trichophyton rubrum (745; 86%) and Trichophyton mentagrophytes (90; 10%) were the most prevalent species among dermatophytes. Dermatophyte infections occurred significantly more frequent in males, whereas yeast and non-dermatophytic molds in females. CONCLUSIONS: The type, and change in etiological factors of fungal infections in patients is a reflection of social behavior modification and changes in the ecosystem of the region and may be an indication for the sanitary epidemiological actions. PMID- 26817330 TI - [Prediction of severe acute pancreatitis--selected prognostic scales and laboratory markers useful in the early stage of the disease]. AB - Early diagnosis of severe acute pancreatitis with its early complications, ie. acute acute respiratory failure, acute kidney injury, or abdominal compartment syndrome, leading to the development of multiple organ failure remains crucial for the survival. It allows for precise selection of high risk patients and enables an early implementation of adequate therapy. The aim of the study was to analyze the current information on potentially useful prognostic scales and markers in the early stage of severe acute pancreatitis. PMID- 26817329 TI - [The influence of age, place of living, education and number of earlier pregnancies on attendance of pregnant women to screening tests--questionnaire study]. AB - The aim of this study was to assess attendance at the screening programme in pregnancy and the influence of age, number of past pregnancies, level of education and place of residence on the attendance. MATERIAL AND METHODS: Our study was performed on the basis of an anonymous questionnaire handed out 543 women aged 16-45, on the third day of their puerperal, in one of the five obstetric wards in southern Poland. The questionnaire contained questions about participation in recommended for pregnant women screening tests such as: fasting blood glucose level measurement, oral glucose tolerance test, blood type test, measurement of hepatitis B surface antigen and antibodies to VDRL, Rubella, Toxoplasma gondii, hepatitis C virus at least once during pregnancy. RESULTS: The highest attendance rate was related with blood type test, whereas the lowest was related with measurement of antibodies to hepatitis C virus (95.6% vs 22.7%, p < 0.001). A very low percentage of pregnant patients measured Rubella antibodies (29.1%). A larger proportion of the respondents checked antibodies against Toxoplasma gondii (41.6%). The attendance at fasting blood glucose level was 66.9 % and at oral glucose tolerance test was 63.7%. The attendance according as age, place of living, number of past pregnancies and level of education was described in detail. CONCLUSION: Despite current recommendations of Polish Gynecological Society and the ordinance of polish Minister of Health the percentage of women participating in screening tests during pregnancy is still insufficient. Age, place of residence and education remain strong factors influencing attendance at the screening programme in pregnancy. PMID- 26817331 TI - [Pregnancy in patients with cardiomyopathy--cases presentation]. AB - It is estimated that 0.2-4% of all pregnancies are complicated by cardiovascular diseases in industrialized countries and the number of the patients with cardiac problems in pregnancy is currently increasing. Cardiomyopathy is a heart disease, congenital or acquired, that may cause heart impairment and as a consequence it may lead to insufficient adaptation under conditions of increased load during gestation. Cardiomyopathy during pregnancy occurs relatively rarely, but potentially it may have severe consequences. Moreover up to 11% of maternal deaths during pregnancy may be caused by cardiomyopathies. We present a series of clinical cases of cardiomyopathy diagnosed before pregnancy. In our observation there are two pregnant women with the hypertrophic cardiomyopathy and one pregnant woman with the dilated cardiomyopathy. Our experience corresponds with previous reports. Pregnancy in the course of cardiomyopathy, leading to changes in blood volume, cardiac output and peripheral vascular resistance, with the limited capacity of the heart, is a therapeutic challenge. The key to the successful therapy is to quantify precisely the risks for both the mother and the fetus. The counseling should be provided by a specialist with appropriate experience, and should be performed in the cooperation with obstetricians, cardiologists and anesthetists. PMID- 26817332 TI - [Hypertrophic cardiomyopathy with midventricular obstruction of the left ventricle (MVO)--case report]. AB - A 76-year old woman with a history of stage 3 arterial hypertension, paroxysmal atrial fibrillation, hypercholesterolemia and type 2 diabetes mellitus. Ventricular tachycardia was the first clinical manifestation of the disease. Echocardiography revealed hypertrophic cardiomyopathy with a high intraventricular gradient of 47 mmHg and midventricular obstruction at the level of the papillary muscles (the lumen of the left ventricle was 1-2 mm during systole). No ventricular aneurysm was found but the ventricle was elongated and dilated in the periapical part where systolic function was decreased but synchronized in time. Coronary angiograms showed no narrowing of coronary arteries. A single-chamber cardioverter-defibrillator (ICD, implantable cardioverter-defibrillator) was implanted to prevent sudden cardiac death. Modified-release metoprolol and amiodarone were administered in antiarrhythmic therapy. This case represents a rare kind of hypertrophic cardiomyopathy in an elderly woman which is characterized by midventricular obstruction. PMID- 26817333 TI - Prevalence of the stages of chronic kidney disease (CKD) according to simplified MDRD formula in patients from ambulatory settings. AB - BACKGROUND: The staging system of chronic kidney disease (CKD) classification plays an important role in patients stratification according to disease activity. The aim of the study was to evaluate the frequency of appearance of consecutive stages of chronic kidney disease based on simplified MDRD formula in patients with diagnosed CKD. Additionally, relationship between eGFR values and selected biochemical parameters and comorbidities were analyzed. METHODS: The study was performed retrospectively in the group of 1176 patients (636 males and 540 females) aged between 17-98 years (mean 64.7) with creatinine level > 120 MUmol/l and/or creatinine clearance < 90 ml/min/1.73 m2. RESULTS: The highest percentage of patients were designated to the 3rd CKD stage. There were positive correlations between eGFR and Hb, Ht, Fe, LDL-Ch, AspAT, HbA1c and negative correlations between eGFR and age, mean and systolic blood pressure, as well as with P, K, iPTH, and uric acid concentration. Patients with cardiovascular diseases had significaintly lower eGFR values as compare with patients without such complications, respectively: atrial fibrillation, arterial hypertension, chronic heart failure, ischaemic heart disease (p < 0.01), and myocardial infarction (p < 0.04). CONCLUSIONS: The highest percentage of patients with diagnosed CKD belong to the 3rd stage of disease. Patients with cardiovascular complications have significantly lower eGFR as compared with those without such disturbances. PMID- 26817334 TI - [Correlations between the lumbrical-interosseous latency comparison test and standard tests used in the diagnosis of carpal tunnel syndrome]. AB - The diagnosis of patients with severe carpal tunnel syndrome (CTS) who do not respond to median nerve stimulation and of those with early CTS who report symptoms but show no abnormalities in standard tests is the most challenging. The aim of the study was to assess correlations between the 2LI-DML test and standard tests used for the diagnosis of CTS (SL-D2, DML-APB, D4M-D4U). The study involved 172 patients (253 nerves) with clinical symptoms of CTS. The sensitivity of the 2LI-DML test and standard tests was analyzed in 6 groups of patients classified according to the severity of CTS, assessed by an electrophysiological study. We showed a significant relationship between the results of the 2LI-DML test and those of standard tests (SL-D2, DML-APB, D4M-D4U), as revealed by a topographic analysis of sensory and motor fibers of the median nerve at the site most vulnerable to compression. PMID- 26817335 TI - [Cigarette smoking--a new path in prophylaxis?]. AB - Not much is known why there are less smokers among girls than among boys. The aim of the study was to investigate what caused a lower incidence of smoking among girls than among boys, and how to make use of this fact in anti-tobacco prophylaxis. MATERIAL AND METHODS: The study was based on surveys and a multiple choice picture test study. A group of 347 adolescents and children attending high schools in Klodawa and the primary school in Gorki were surveyed. Their reason for not smoking were obtained by means of surveys, and factors discouraging them from smoking were checked by means of a multiple choice picture test. RESULTS: Not making any attempt at tobacco smoking significantly influenced nonsmokers (Chi2 = 4.81, p = 0.028). Nausea after smoking a cigarette led 9.7% of girls and 4.3% of boys to give up smoking. In terms of the adverse effects of smoking, children up 12 years of age feared nausea, and from the age of 12, feared impotence and infertility, more than neoplastic diseases. CONCLUSIONS: In anti tobacco prophylaxis, it is necessary with children not yet at the age of puberty to point out nausea as a harmful consequence of smoking, and with children from the age of 12, to indicate infertility and impotence as consequences. We should also inform them about the harmful impact of smoking on beauty, and the incidence of obesity in smokers' offspring. We also need to increase emphasis in prevention efforts on the need to not start smoking. PMID- 26817336 TI - [Tribute to the Righteous Among the Nations Polish doctors and medical students]. AB - 52 Polish doctors and medical students received the Righteous Among the Nations title awarded by the Yad Vashem remembrance authority in Jerusalem for having saved the life of a Jew during the Holocaust or having tried to recue a Jew who was helpless and facing death or deportation. We have an obligation to remember these Righteous doctors, who were spurred in World War II by the "banality of good", so that future generations can identify with the anonymous survivors who demonstrated such generosity, humanity, and courage and who put their own lives at risk. PMID- 26817337 TI - [Personality of medical students declaring surgical specialty choice in the context of prospective medical practice style]. AB - INTRODUCTION: Specialty choice made by medical students takes into account the nature of future medical practice. Holland's congruence theory, according to which career choice is treated as an expression of personality characteristics common for all representatives of the same profession, has served as a theoretical background for own research on the subject matter. Spectacular exemplification of fit between mental resources--personality characteristics and working environment requirements, is the concept of distinct surgical personality (DSP), widely discussed in worldwide literature of the subject (although not in native one). The article offers an author's broadened perception of DSP conception encompassing not only personality characteristics, but also values preference. AIM: The research aims at verifying the hypothesis that a given personality constellation directs the choice of surgery as a prospective specialty made by medical students, as well as allows predicting the style of future vocational practice, characterized by dominant instrumental activities, with little emphasis on affective medical actions, typical for technique-oriented specialties. MATERIALS AND METHODS: The study involved a total of 223 students of fourth year of medical studies at Medical University of Lublin. Students declaring their choice of surgical specialty constituted the criterion group (N = 93). The control group comprised of students who declared their choice of person oriented specialties, aimed at work with patient approached holistically (N = 75), in accordance with dichotomous specialty division adopted for the research purposes. Polish adaptations of NEO Five-Factor Inventory (NEO-FFI) by Costa and McCrae and Schwartz Value Survey were applied. RESULTS: The use of multivariate logistic regression indicates three crucial predictions of surgical specialty choice: 'neuroticism' and 'agreeableness' (personality trials-negative predictors) and 'self-enhancement' (value meta-category - positive predictors), however the latter variable has the strongest impact on the choice. The tested model comprising both personality characteristics and allows proper classification of 85% respondents declaring their surgical choice. CONCLUSION: Personality constellation of prospective surgical adepts appears to be a coherent and strong predictors of medical practice style characteristic for surgery--with strong biotechnical orientation, and predisposition to building paternalistic relations with patients in interpersonal layer. The personality of surgeons-to-be corresponds with functional requirements of surgical treatment, nevertheless their readiness to adequate reaction on non-medical patients' needs requires designing educational process so that it activates values complementary to 'power' and 'achievement', mainly 'universalism', viewed as perceiving others as equal to self. PMID- 26817338 TI - [Metformin and changes in blood pressure and heart rate in lean patients with polycystic ovary syndrome (PCOS)--preliminary study]. AB - INTRODUCTION: The aim of our study was to assess the value of blood pressure and heart rate using the 24-hour blood pressure monitoring (ABPM) before and after treatment with metformin to patients with polycystic ovary syndrome (PCOS) and normal lean. MATERIAL AND METHODS: 5 patients received metformin 1500 mg per day in three divided doses. ABPM was performed to each patient with PCOS twice: before and after 6 months of treatment with metformin. RESULTS: In patients with PCOS and normal lean after treatment with metformin we observed: statistically significant lower systolic blood pressure (120.2 +/- 22.33 mmHg vs 113.22 +/- 21.43 mm Hg, p = 0.0248); lower systolic blood pressure of daily measurements (127.1 +/- 32.13 mmHg vs 116.1 +/- 22.08 mmHg, p = 0.0062); reduction in average arterial pressure MAP in the measurement of the day (95.52 +/- 22.76 mmHg vs 88.36 +/- 16.41 mmHg, p = 0.048); oscillometric pressure reduction (96.27 +/- 27.93 mmHg vs 87.82 +/- 21.61, p = 0.0004 mmHg); oscillometric pressure reduction of daily measurements (102.1 +/- 27.93 mmHg vs 91.85 +/- 21.61 mmHg, p = 0.0032); oscillometric pressure reduction in the measure- ment of the night (88.81 +/- 24.85 mmHg vs 82.22 +/- 20.54 mmHg, p = 0.0089). In women after treatment with metformin has also been observed higher average heart rate (65.82 +/- 13.48 / min vs. 70.71 +/- 16.04 min; p < 0.01). The calculations included 500 measurements. CONCLUSION: Treatment with metformin in patients with PCOS and normal lean leads to lower blood pressure and increases the frequency of heart rate. PMID- 26817339 TI - [Renalase and its role in the development of hypertension in patients with chronic renal failure]. AB - Renalase is a newly-discovered enzyme--amine oxidase containing flavin adenine dinucleotide that determines its activity. Kidneys are the main source of renalase, however, the enzyme has also been detected in the myocardium, skeletal muscles, small intestine, peripheral nerves, adrenal cortex and adipose tissue. This enzyme metabolizes circulating catecholamines, particularly epinephrine and L-3,4-dihydroxyphenylalanine (a dopamine precursor). For this reason, it is considered that renalase may play a significant role in the regulation of blood pressure. There are some factors enhancing the release of renalase: rising catecholamines levels in the circulation and increase in blood pressure. Experimental and clinical studies revealed renalase deficiency in chronic kidney disease (CKD) and hypertension. In contrast, the results of assays based on currently available ELISA kits demonstrate an increase in renalase concentration in patients with CKD. On the basis of currently available studies it is difficult to determine how important are changes in the expression and secretion of renalase in the pathogenesis of hypertension in CKD patients. Stimulation of catecholamines degradation, perhaps using recombinant renalase or its analogues, is a new concept in the treatment of hypertension in CKD. PMID- 26817340 TI - [Blood pressure and polycystic ovary syndrome (PCOS)]. AB - Polycystic ovary syndrome (PCOS) is the most common endocrine disorder occurring in women of childbearing age. The literature describes the relationship between PCOS and high blood pressure levels and increased risk of arterial hypertension development, which is an important and strong risk factor for adverse cardiovascular events in the future. Among the main causes of hypertension in PCOS women insulin resistance, hyperandrogenism, greater sympathetic nerve activity and concomitance of obesity are stressed. Because PCOS may contribute to earlier development of hypertension, as well as pre-hypertension, therefore it is advisable to monitor blood pressure systematically, to control known risk factors, and to initiate the treatment of hypertension when the disease occur. PMID- 26817341 TI - [Sheehan's syndrome--a forgotten disease with 100 years' history]. AB - Although named after Harold Sheehan, postpartum ischemic pituitary necrosis was reported for the first time 100 years ago in Przeglad Lekarski by Leon Konrad Glinski. In the majority of cases, the syndrome is a consequence of severe postpartum bleeding episode resulting in severe hypotension or hemorrhagic shock. The frequency of Sheehan's syndrome has decreased in developed countries as a result of improved obstetrical care, but this clinical entity remains a common cause of hypopituitarism in developing countries. The syndrome is characterized by varying degrees of anterior pituitary dysfunction resulting from the deficiency of multiple pituitary hormones. The order of frequency of hormone loss has generally been found to be growth hormone and prolactin, gonadotropins, ACTH and thyrotropin. Women with Sheehan's syndrome exhibit a variety of signs and symptoms including failure to lactate or resume menses, loss of genital and axillary hair, and often occurring long after delivery clinical manifestations of central hypothyroidism and secondary adrenal insufficiency. Diagnosis is based on laboratory studies, including hormone levels and hormone stimulation tests. Treatment of Sheehan's syndrome involves hormone replacement therapy. The aim of this study is to review current knowledge on clinically relevant aspects of this clinical entity and to provide the reader with recommendations concerning its diagnosis and treatment. PMID- 26817342 TI - Eosinophilia in patient with acute cellular rejection after liver transplantation -case presentation and literature overview. AB - Acute cellular rejection (ACR) is still an important problem affecting patients after liver transplantation. Early diagnosis is necessary for initiate treatment, but there are not simple, noninvasive methods to confirm the diagnosis, and up to now, the gold standard in the evaluation of ACR is liver biopsy. The blood eosinophilia seems to be a promising tool supporting the diagnosis and monitoring the effectiveness of ACR treatment in patients after liver transplantation. In this paper a young patient transplanted due to primary sclerosing cholagitis with blood and graft eosinophilia is presented. Based on this interesting case, the literature overview is presented. We conclude that blood eosinophilia, especially with concomitant increase of gamma-glutamyl transpeptidase activity and bilirubin concentration could be an effective tool to predict ACR and may help to choose the. PMID- 26817343 TI - [Cutaneous involvement in multiple myeloma--case report and literature review]. AB - Cutaneous involvement in multiple myeloma is a very rare clinical problem. It occurs in less than 1% myeloma patients. Skin manifestation may be primary or secondary to MM. Primary involvement (PCP) according to the current WHO classification is one of the marginal zone lymphomas of the skin. PCP are characterized by significantly better prognosis than infiltrations secondary to MM. Skin manifestations require a thorough diagnosis to differentiate between myeloma-specific changes, MM-associated and non-specific skin disorders. Isolated primary infiltration can usually be successfully treated with radiation therapy or surgery. So far treatment of multiple and secondary to MM involvement are not satisfactory. PMID- 26817344 TI - [Erythema exudativum multiforme--case report]. AB - Erythema exudativum multiforme (EM) is an acute mucocutaneous disease. Etiology of this disease is not clear. 50% - 60% cases of EM is induced by HSV infection (herpes simplex virus 1, herpes simplex virus 2). EM lesions may appear as red macules, erosions, ulcerations and hemorrhagic crusts. The study describes the case of 22 - year - old male who had characteristic lesions for EM after HSV infection. PMID- 26817345 TI - "Pros and cons" of total hip arthroplasty with metaphyseal Proxima endoprosthesis. AB - The authors present their own experience concerning total hip arthroplasty with the metaphyseal prosthesis Proxima. Proxima, a metaphyseal prosthesis, provides an innovative supplement to total hip arthroplasty. In this study, the authors present their own experience using Proxima in patients with hip osteoarthritis. This study was performed between 2008 to 2013 and comprised of 62 patients, of which 38 were male (61.3%) and 24 female (38.7%). All patients were operated on due to hip osteoarthritis using total hip arthroplasty with the metaphyseal prosthesis Proxima. The age of patients included into the study ranged from 23 years to 62 years with the mean age of 46 years. The authors paid close attention to the "pros and cons" of surgical techniques and assessed clinical and radiological results in both the short and long-term observation periods. The clinical evaluation was based on the Harris Hip Score and radiological assessment of fixation of the acetabular cup of the endoprosthesis was based on Pradhan's criteria. The endoprosthesis Proxima stem was positioned using the manufacturer's recommended method, evaluating the direction, scope and duration of the displacement in the marrow cavity of the proximal stump of the femur. According to the authors' analysis, the surgery gives good functional and radiological results both in the short- and long-term observation periods. The effectiveness depends on precise qualification for surgery, proper surgical techniques and specific anatomical conditions of the proximal femur stump. The most common reasons for primary and secondary dislocations of the metaphyseal endoprosthesis Proxima stem occur during the first three months post surgery. This is due to incorrect surgical techniques, which disregard the importance of specific anatomical conditions of the proximal femoral stump, which affects Proxima implantation, and cause deviations towards a varus or valgus orientation. PMID- 26817346 TI - [The influence of tocolytic drugs usage in the third trimester of pregnancy on obstetric and neonatal outcomes]. AB - INTRODUCTION: The occurrence of preterm labor is the cause of 75% of preterm births. Prematurity is the leading cause of mortality of children under four weeks of age. Tocolytic drugs are used widely in the treatment of preterm labor. The aim of this study was to assess the impact of the tocolytic therapy on obstetric and neonatal outcomes. MATERIAL AND METHODS: The prospective, cohort study included 499 pregnant women The study enrolled women who met certain criteria of age, with singleton pregnancy, having no chronic diseases. After delivery the following data were obtained: sociodemographic profile (including data on occupational activity), body height and weight before pregnancy, weight gain, duration of pregnancy, mode of delivery, obstetric complications, medications, anthropometric parameters and state of health of newborns. A group of patients treated with tocolytic drugs and a control group were identified. Then obstetric and neonatal outcomes in both groups were subjected to statistical analysis. RESULTS: There was no statistically significant difference between the two groups in terms of the following variables: mother's age, her education, professional activity of mothers in the first and second trimester of pregnancy, weight gain during pregnancy, parity, exposure to passive smoking during pregnancy, method of pregnancy termination. We found a statistically significant difference between the groups with respect to maternal weight before pregnancy (lower in the group using tocolytics), the average duration of pregnancy (lower in the group using tocolytics), the frequency of preterm birth (higher in the group using tocolytics) and neonatal anthropometric parameters and the number of points in the Apgar score at 5 minutes of age (lower in the group using tocolytics). CONCLUSIONS: Low pregestational weight is a risk factor for preterm labor. Term birth rate in pregnant women treated for preterm labor is significantly smaller compared to the general population, which may indicate low efficacy of tocolytic drugs. There was no positive correlation found between the professional activity of pregnant women and the risk of threatening preterm labor. PMID- 26817348 TI - Proinflammatory cytokines in periodontal diseases and certain systemic disorders. AB - Recent decades have brought significant progress in understanding the role of cytokines in many aspects of the development of periodontal disease associated with systemic disorders and increased risk of oral cancer. A thorough search of articles was carried out on the databases PubMed on the association of periodontal disease and obstetric pathologies, systemic diseases and cancer. Refs cited are examples of support already common idea that periodontal disease may affect the initiation and/or development of serious pathological conditions. Drawn from the literature review findings confirm that chronic untreated periodontal inflammatory processes have their own important part in promoting systemic diseases and also are associated with an increased risk of developing cancer diseases. PMID- 26817347 TI - [Do we successfully treat anemia and calcium-phosphate disorders in children with chronic kidney disease at the beginning of the twenty-first century?]. AB - In children with chronic kidney disease (CKD) anemia and calcium-phosphate disturbances are already present at early stages of the disease and require a comprehensive treatment. The aim of this study was to evaluate the efficacy of the treatment of biochemical disturbances, depending on the severity of CKD in children. MATERIAL AND METHODS: The study included 71 children (44 boys, 27 girls) with CKD stage 1-5. Mean age was 11 +/- 5 years, mean height: 135.7 +/- 28 cm and mean eGFR 32 ml/min/1.73 m2. The serum hemoglobin, urea, creatinine, cystatin C, calcium, phosphorus and parathyroid hormone (PTH) levels were measured. eGFR was calculated according to Schwartz and Filler formulas, employing creatinine and cystatin C as markers. Patients were divided into groups depending on the stage of CKD [group 1: CKD stage 1+2 (GFR > 60), group 2: CKD stage 3 (GFR = 30-59) Group 3: CKD stage 4 (GFR = 15-29 ml/min/1.73 m2), group 4 dialyzed children]. RESULTS: The concentration of he- moglobin depending on the stage of CKD (group 1 vs. group 2 vs. group 3 vs group 4) was 12.95 vs. 12.68 vs. 12.47 vs. 11.3 g/dI, respectively. The concentration of total and ionized calcium was significantly lower in children on dialysis compared to patients treated conservatively. With the progression of CKD the concentration of phosphorus (1.39 vs. 1.4 vs. 1.49 vs. 1.82 mmolI) and PTH (21.7 vs 48.6 vs 99.9 vs. 219 pg/ml) significantly increased. Treatment with erythropoietin was used in 48% of children, calcium carbonate in 55% and alphacalcidol in 56% of patients. CONCLUSIONS: Despite the use of regular treatment, with the progression of CKD a progression of anemia, increased serum phosphate and parathyroid hormone and a decrease in calcium levels in studied children was observed. The severity of metabolic disorders in dialyzed children indicates the need for administration of new and more effective drugs, to prevent early enough complications of CKD in the form of mineral bone disease and cardiovascular complications. PMID- 26817349 TI - [Retinoblastoma: genetic background, modern diagnostic methods and therapies]. AB - Retinoblastoma is the most common intraocular eye tumor of the pediatric age. It develops on account of a mutation on chromosome 13 in the 13q14 locus. New studies additionally demonstrated changes in the expression of other genes classified as oncogenes and suppressor genes. The tumor occurs in two forms- heritable (genetic) and non-heritable (non-genetic, sporadic). The most common clinical features of retinoblastoma are leucocoria and strabismus, however, they are not that specific because may also occur in several other eye diseases, such as Coats disease and toxocarosis. The diagnosis of retinoblastoma requires an indirect ophthalmoscopic examination. In addition, imaging techniques such as ultrasonography (USG), magnetic resonance imaging (MRI) and, less commonly, computer tomography (CT) are used. Biopsy is contraindicated because of the risk of spreading cancer cells to the adjacent tissues and possibility of a metastasis development. Currently, the stage of the disease and the therapy prognosis are classified by the International Intraocular Retinoblastoma Classification. At present, chemotherapy is the standard treatment of retinoblastoma. During the last decades new therapies have been introduced, such as transpupillary thermotherapy (TTT), cryotherapy, brachytherapy, limiting the use of teletherapy and the number of performed enucleations. Patients with therapy-induced remission of retinoblastoma should undergo routine examinations because of the increased risk of subsequent neoplasms and other possible complications. PMID- 26817350 TI - [Clinical variability of Juvenile Huntington's Disease phenotype]. AB - Huntington's disease is rare, genetically determinated, neurodegenerative disorder. It is determined by dynamic mutation of IT15 gene on short arm of 4 chromosome. Characteristic symptomatology include involuntary movements, cognitive decline and wide spectrum of mood and behaviour disorders. It typically becomes noticeable in mid-adult life, but there are reported cases of appaers of symptoms between 2 and 80 year of life. Especially interesting is juvenile Huntington's disease- the Westphal variant with the beginning in childchood (before 20 year of age) because of clinical differences causing diagnostic difficulties. It affects 5-10% of carries of the mutant gene. Symptoms became noticeable before 10 year of age only in 1% of them. PMID- 26817351 TI - [Transcranial magnetic stimulation in psychiatric therapy]. AB - Transcranial magnetic stimulation (TMS) is one of new techniques of the physical treatment in psychiatry. Its advantage is painlessness, so as lack of invasiveness and evoking a convulsive effect. The technique of TMS was introduced into the clinical practice in 1985--originally as a diagnostic method in neurology. Later TMS became a valuable tool in the basic research in neurophysiology and neuropsychology, so as in clinical examinations. In 1994 the first papers on TMS application in therapy of depression and schizophrenia were published. The research on the therapeutic TMS effectiveness encounters certain problems and restrictions: difficulties in determining a place of the stimulation, lack of the possibility of the selection of optimal parameters for the stimulation, problem in guarantying optimal conditions for the double-blind study, etc. During the last two decades TMS was applied in therapy of mood disorders and psychoses more on the principle of consuetude, than confirmations of the evident effectiveness. However recently a group of European experts presented the study, in which they regarded TMS as the effective method in therapy of depression and schizophrenia--presenting conditions to the optimal stimulation. PMID- 26817352 TI - [Intrauterine growth restriction--diagnosis and treatment]. AB - The prevalence of low birth weight affects approximately 3-10% of live-born newborns in developed countries and in developing countries it affects 15-20% of newborns. The most common cause of low birth weight is considered to intrauterine fetal growth resctriction. Low birth weight is responsible for 69.6% of stillbirths and for 66.4% of neonatal deaths. The purpose of this paper is to review reliable scientific data in order to summarize the current guidelines on intrauterine fetal growth restriction, addressed to obstetricians. The present review is based on guidelines of the American College of Obstetricians and Gynecologists (ACOG), the Royal College of Obstetricians and Gynaecologists (RCOG), the Society of Obstetricians and Gynaecologists of Canada (SOGC), the results of DIGITAT- (ang. The Disproportionate Growth intrauterine Intervention Trial At Term) PORTO Study- (ang. Prospective Observational Trial is the Opitimize Pedriatric Health in intrauterine Growth Restriction), TRUFFLE- (ang. Randomized Trial of Fetal and Umbilical Flow in Europe), and the available literature. PMID- 26817353 TI - Adenoid cystic carcinoma of the external auditory canal with metastases to lymph nodes and lungs--problematic diagnosis and treatment based on a case report. AB - Adenoid cystic carcinoma (ACC) of the external auditory canal (EAC) is an exceedingly rare tumor. Despite the slow growth it is characterized by a high malignancy and infiltration of surrounding tissue. Differential diagnosis may be especially difficult if the tumor appears in an atypical localization as it can present with non-specific features. The optimal treatment of this malignancy has not been fully established. We present a case report of a 55-year-old man with ACC of EAC metastasizing to the lymph nodes, lungs and vertebrae, with intracranial involvement. The patient was initially diagnosed with basal cell carcinoma (BCC) of EAC based on MR imaging examinations and excisional biopsy from EAC. Current information about nomenclature, epidemiology, characteristic features and treatment possibilities of ACC are presented and difficulties in making diagnosis are discussed. ACC should be considered among the malignant tumors of EAC. Its natural behavior is probably more unpredictable than commonly thought. Similar cases are rare and our knowledge about the tumor's specificity and prognosis is limited. PMID- 26817354 TI - [The ovarian origin of hiperandrogenism in the postmenopausal woman the adrenal adenoma--a case report]. AB - Hyperandrogenism is a clinical condition characterized by excessive secretion of male sex hormones. An excess amount of androgens in women is manifested by symptoms of defeminization and masculinization. Hormonally active adrenal and ovarian tumors and non-tumor causes must be considered in the differential diagnosis. The authors describe the case of a 77-year-old patient who had hirsutism and reduction of the timbre of the voice. At the beginning she was suspected to have adrenal hyperandrogenism because of the tumor in the adrenal gland. Then adrenalectomy was conducted but it did not lead to alleviate symptoms. A MRI of the pelvis revealed a change of appendages projection and the patient underwent the total hysterectomy. The normalization of testosterone levels as well as reduction of the symptoms was observed after the operation. Finally, the ovary etiology of hyperandrogenism was confirmed. This case report is an example of difficulties in recognition the etiology of hyperandrogenism. PMID- 26817355 TI - [Dural metastatic infiltration in prostate cancer--case report]. AB - Metastatic changes secondary to prostate cancer usually occur in bones, less commonly in pelvic lymph nodes, liver, lungs, urinary balder and brain. Less common localization includes skin, testis and other structures. The current paper reports a rare case of metastatic infiltration of the dura mater in patient with prostate cancer (Gleason 8 (4+4)) with disseminated bone metastasis. Magnetic resonance imaging revealed an advance infiltration of dura mater of anterior and posterior cranial fossa without any neoplasmatic-related changes in brain. Along optic nerves it penetrated to the optic canal and right orbit. PMID- 26817356 TI - [Pseudocyst of the umbilical cord--case report]. AB - A case of umbilical cord pseudocyst in the first pregnancy in a 30-year old female patient. In this study the authors presents the course of pregnancy, ultrasound description, parturition and the evaluation of the newborn after birth. Using the available literature ultrasound compared with the documentation and the prognosis for the fetus. Preparing a case searched Medline for analysis of previous studies and descriptions of the umbilical cord cyst in the second trimester of pregnancy. Due to the correlation with aneuploidy and lethal defects, it was found that the visibility of cystic masses within the umbilical cord, regardless of the gestation period should be an indication for the intensive monitoring of fetal ultrasound and referral center for testing fetal karyotype. PMID- 26817357 TI - [Neuralgic amyotrophy--a case report]. AB - We describe a case of a 54-year-old woman reporting weakness of the right upper limb, preceded by a period of severe pain in the right shoulder. Despite several orthopedic consultations and two cycles of physical therapy, the symptoms deteriorated over a period of 6 months, and progressive paresis of the extensor muscles of the upper limb and elbow flexion contracture were observed. On the basis of the clinical presentation and results of medical tests including an electrophysiological study that showed axonal damage to the long thoracic nerve, axillary nerve, and posterior interosseous nerve, neuralgic amyotrophy was diagnosed. A treatment with prednisone was introduced, and the patient's condition significantly improved. PMID- 26817358 TI - [Long-term consequences of resection of 1/3 proximal epiphysis of child's right tibia--a case study]. AB - Authors report a case of a patient with varus deformity of right knee, caused by wide resection of proximal metaphysis and epiphysis of right tibia. Afore mentioned procedure led to loss of right knee joint integrity, with its lateral instability, shortening, and axis deviation of right tibia. Surgical treatment of this complications was performed in several stages and took about 5 years, starting from temporal, lateral hemiepiphysiodesis of proximal tibial epiphysis, subacute epiphysiolysis of proximal tibial epiphysis and high valgus tibia osteotomy, at the end finished with medial tibia condyle reconstruction with autogenic graft and osteoconductive substances. The proper mechanical and anatomical axis of the right limb, with full stability and movement of right knee was achieved after those surgeries. The process of treatment of lower extremity axis deviation takes long time, frequently involves several surgeries and needs firm cooperation between doctor and patient. PMID- 26817359 TI - [Stefan Czubalski. Member of the Founding Committee of the Polish Urological Society. Biographical note]. PMID- 26817360 TI - New Year's Resolution: Be Transformed! PMID- 26817361 TI - Humility: A Noun, Adjective, and a Verb? PMID- 26817362 TI - What Are the Challenges for APNs As Educators? PMID- 26817363 TI - Norma Small--Faith Community Nursing Pioneer (1936-2015). PMID- 26817364 TI - Sex in the Nursing Home. PMID- 26817365 TI - Faith, Hope, and Spirituality: SUPPORTING PARENTS WHEN THEIR CHILD HAS A LIFE LIMITING ILLNESS. AB - When a child has a life-limiting illness, parents' goals and strategies for their child's life may need to be drastically altered, especially if early death looms. This article reviews literature and research about how families employ faith, hope, spirituality, and biblical perspectives as their child becomes critically ill and faces death. Suggestions are made for best caring practices for families and children encountering this difficult journey. PMID- 26817366 TI - When Sorrow Never Stops. Chronic Sorrow After the Death of a Child. AB - The death of a child, regardless of age, is the most horrendous, severe, and debilitating form of bereavement a parent can experience. Two authors--one who lost her son and one who has a son with intellectual limitations--explain how the Theory of Chronic Sorrow offers help in understanding the grieving process and how nurses can assist parents and others experiencing long-term bereavement. PMID- 26817367 TI - Chronic Sorrow Revisited: Watching My Son Struggle. PMID- 26817368 TI - Patient Storytelling in the Classroom: A Memorable Way to Teach Spiritual Care. AB - Storytelling is an evidence-based teaching and learning strategy that engages students and promotes critical thinking. Although most nursing textbooks incorporate spiritual nursing care, the texts lack examples of how to tie evidence-based spiritual interventions to specific medical-suigical content. Stories told from the patient's perspective can communicate insights that nurses and students can use when planning spiritual carefor patients. Stories shared by patients with undergraduate nursing students were effective in promoting learning and offered concrete examples of supportive spiritual resources for patients. PMID- 26817369 TI - Growing Healing One Garden at a Time. AB - Evidence exists regarding the effect of horticultural therapy on improving human well-being, including promotion of overall health and quality of life, physical strength, and cardiac function. This article shares how a nurse created a healing garden at Lourdes Hospital, where she works. Resource information about therapeutic gardens is included. PMID- 26817370 TI - RELIGION & CARE INTERTWINED; NURSING IN CATHOLIC HOSPITALS 1950-1965. AB - This qualitative study explores how Catholicism influenced nursing in Catholic hospitals and how nurses met the religious needs of Catholic patients in the 1950s and early 1960s. Six nurses were interviewed who graduated from Catholic schools of nursing between 1952 and 1965 and worked in Catholic hospitals. Results indicate that nursing care was inexorably entwined with meeting the religious needs of Catholic patients. Religious practices were predictable and largely linked to the Holy Sacraments. PMID- 26817371 TI - CARING FOR THE VULNERABLE: AN EXPLORATION OF GUATEMALAN HEALTHCARE ISSUES. AB - Knowledge of health practices and concerns is one key to providing culturally sensitive care to persons of different ethnicities. It is estimated that Guatemala is the third leading source of undocumented immigrants in the US. To increase understanding of Guatemalan healthcare issues, a descriptive study asked what are common healthcare issues among rural, indigenous Guatemalans and Guatemalan immigrants to the United States, and how do these issues compare? PMID- 26817372 TI - You Are Not Alone: PARISH NURSES BRIDGE CHALLENGES FOR FAMILY CAREGIVERS. AB - In 2015, there were 43.5 million informal, unpaid caregivers in the United States. Caregivers reported a moderate to high level of burden of care, including performing medical and nursing tasks they were not trained to do. A study of family caregiver experiences with parish/faith community nurses reveals four key ways parish nurses support caregivers and offers important implications for parish nurse preparation and practice. PMID- 26817373 TI - New Poetry Initiative! PMID- 26817374 TI - Nurse-poet Kristina Ibitayo. Interview with Sharon Fish Mooney. PMID- 26817375 TI - What Makes for Culturally Sensitive Spiritual Care? PMID- 26817376 TI - Lifelong Learning in Nursing. PMID- 26817377 TI - A Path Unpredicted. PMID- 26817378 TI - Phenolic compounds content and antioxidant capacity of meals provided to elementary public schools in Chile during 2011. AB - The Chilean National School Feeding Program (NSFP) delivers breakfast and lunch meals that supply 250 and 450 kcal, respectively, along the country. In the last decades, a significant increase of obesity has been observed in primary education children, and it involves risk factors of non-communicable diseases. The dietary intake of foods containing phenolic compounds (PC) exerts favorable effects on health by reducing risk factors of prevalent diseases. The aim of the study was to measure the PC content and antioxidant capacity (AC) [ORAC and DPPH] of meals provided by the NSFP in Quillota, Chile, in 2011. The PC supply of the whole meals served ranged from 362.7 to 1,730 mg GAE. The best breakfast foods include whole grain cookie (2.59 +/- 0.3 mg GAE/g), bread with avocado, quince jelly or strawberry jam (1.61 +/- 0.13 to 2.05 +/- 0.3 mg GAE/g); while the best lunch salads include beetroot, lettuce, and cabbage/fish (1.66 +/- 0.3 to 2.35 +/- 0.1 mg GAE/g), and main courses contain legumes, or mixed vegetables. The lowest PC contents were observed in pasta and rice preparations (p < 0.05). Among desserts, the best source of PC is fruit (1.81 +/- 0.04 to 6.91 +/- 0.31 mg GAE/g). The correlation between PC and AC varied according to the type of meal. PC content and AC are additional criteria for selecting the best quality meals, in addition to the nutrients and energy content. The results support the recommendation to increase the supply of fruits and vegetable/legumes preparations and fruits instead of starchy foods to scholars. PMID- 26817379 TI - [Glycemic index of two varieties of pasta and two varieties of rice]. AB - The IG has been extensively studied as an indicator of the physiological effects of a carbohydrate meal with applications in the management and prevention of diabetes, dyslipidemia and obesity. A standard assay was performed to measure the glycemic index (GI) of two significant sources of carbohydrates following the World Health Organization (WHO) recommended methodology, determining the incremental area under the blood glucose response curve of a 50g carbohydrate portion of the test food compared to the same amount of carbohydrate from a glucose solution by the same subject measured in capillary whole blood before and 15, 30, 45, 60, 90 and 120 minutes after ingestion in a total of 9 subjects. The following results were obtained: Parboil rice: 73, Long Grain White Rice: 59; Pasta of durum wheat (Triticum durum): 71, Pasta of regular flour (Triticum aestivium): 38. This test confirms the low glycemic index of pasta made from durum wheat, and is the first measurement for pasta of common wheat flour properly characterized. It also indicates the values of the prevailing presentations of rice in the region, adding a reference for professionals and authorities. PMID- 26817381 TI - [Study of food characteristics of Uruguayan adolescents]. AB - The aim of this study was to characterize the diet of Uruguayan adolescents and demographic aspects that influence it. The data come from the National Survey of Adolescents and Youth in 2008 which worked with 2,943 cases, representative sample of all adolescents in Uruguay. The characteristics of feeding studied were: consumption of fruits and vegetables, soft drinks, fast food, added salt to meals served at the table and meal times shared with a parent. These variables were also studied in aggregate to determine a pattern of eating behavior. It was found that 89% of adolescents did not meet the recommendation of 5 servings of fruits and vegetables a day, 50% consumed daily soft drinks, fast foods ingested 24% 2 or more times per week and 13% added salt at all preparations. We also found that 31% did not share mealtimes with parents daily. By adding the variables studied, we observed that 58% were inadequately fed, and is higher among older adolescents (p < 0.01), who had higher household income (p < 0.05) and those who were not residing in the capital (p < 0.05). It is concluded that feeding adolescents was characterized by inadequate intake of fruit and vegetables, frequent consumption of soft drinks, fast food and adding salt to served meals, which defined it as inadequate. This was mainly observed in older adolescents, better economic situation and residents within the country.. PMID- 26817380 TI - Association between maternal diet factors and hemoglobin levels, glucose tolerance, blood pressure and gestational age in a Hispanic population. AB - The aim of this study was to describe the dietary patterns of pregnant women in northern Puerto Rico and explore associations between diet factors with pregnancy related measurements. This analysis is based on the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT), a prospective cohort that is studying environmental risk factors for preterm births in PR. Participants completed a food frequency questionnaire (FFQ) around 20-28 weeks of gestation. The following pregnancy related measures were collected from the medical records: hemoglobin, blood glucose, blood pressure and gestational age. Potential associations between diet factors and pregnancy measures were assessed using chi square analysis with SPSS. A total of 180 participants completed the FFQ; low hemoglobin levels was found in 19.2%, high blood glucose levels was found in 21.1% by fasting blood glucose test and 24.6%by 1-hour 50 g oral glucose screening test, high blood pressure was found in 2.9% (systolic) and 6.5% (diastolic), and pre-term birth was found in 10.4% of the participants. High consumption of rice, desserts and sweets was associated with higher levels of fasting blood glucose levels (p < 0.05), while high consumption of vegetables was associated with higher 1-hour glucose challenge test (p < 0.05).No other significant associations were found. In conclusion, consumption of high dense energy food diets in pregnancy, such as rice, sweets and desserts, can lead to high levels of blood glucose and can be a potential predictor of other pregnancy complications during pregnancy in these study participants, such as gestational diabetes. PMID- 26817382 TI - [Assessment, evaluation and nutrition monitoring in older people living in a rest home]. AB - Institutionalized elderly have an increased risk of changes in nutritional status, therefore sensitive parameters are necessary for the identification of changes in nutritional status. The aim of this study was to evaluate parameters for analysis of the nutritional status of institutionalized elderly in a period of three months by means of biochemical and anthropometric measurements. Eighty one volunteers were selected, with 78 +/- 10 years old and 53% female. Anthropometric data showed that the variables body mass index, weight, fat mass, and phase angle of the institutionalized elderly in three months decreased with significant difference between the assessments. Among all the biochemical and anthropometric measurements, body mass index, weight, fat mass, phase angle and blood fat were the indicators of nutritional assessment that identified early changes and nutritional risks of institutionalized elderly in three months. It is noteworthy that the early evaluation of nutritional indicators can prevent nutritional risk among elderly in living in rest homes. PMID- 26817383 TI - [Microstructural changes in hardened beans (Phaseolus vulgaris)]. AB - (Phaseolus vulgaris). The hardening of Phaseolus vulgaris beans stored at high temperature and high relative humidity is one of the main constraints for consumption. The objective of this research was to evaluate by scanning electron microscopy, structural changes in cotyledons and testa of the hardened beans. The freshly harvested grains were stored for twelve months under two conditions: 5 degrees C-34% RH and 37 degrees C-75% RH, in order to promote hardening. The stored raw and cooked grains were lyophilized and fractured. The sections of testa and cotyledons were observed in an electron microscope JSM-6390. After twelve months, grains stored at 37 degrees C-75% RH increased their hardness by 503%, whereas there were no significant changes in grains stored at 5 degrees C 34% RH. At the microstructural level, the cotyledons of the raw grains show clear differences in appearance of the cell wall, into the intercellular space size and texture matrix protein. There were also differences in compaction of palisade and sub-epidermal layer in the testa of raw grains. After cooking, cotyledon cells of the soft grains were well separated while these ofhard grains were seldom separated. In conclusion, the found differences in hard and soft grains showed a significant participation of both structures, cotyledons and testa, in the grains hardening. PMID- 26817384 TI - Synergistic, additive and antagonistic effects of fruit mixtures on total antioxidant capacities and bioactive compounds in tropical fruit juices. AB - The objective of this work was investigate the synergistic, additive and antagonistic effects of fruit mixtures on total antioxidant capacities and bioactive compounds in tropical fruit juices, and optimize its formulation by the response surface methodology based on the responses: total polyphenols (TP), total antioxidant capacity (TAC), ascorbic acid content and sensorial acceptance. Camu-camu, acerola and acai were the major factors that influenced the antioxidant potential of the juice; and the yellow mombin showed a positive effect on the acceptance of the tropical juice. It was observed an/antagonistic effect between acerola and camu-camu for the TAC response. The optimum formulation obtained was 20% acerola, 10% camu-camu, 10% yellow mombin, 10% cashew apple and 10% acai, which was responsible for a response of 155.46 mg.100 g(-1) of ascorbic acid, 103.01 mg of GAE.100 g-1 of TP, 10.27 uM Trolox g(-1) of TAC and approximately 6.1 of acceptance. PMID- 26817385 TI - [Physical and antioxidant characteristics of black (Brassica nigra) and yellow mustard (Brassica alba) seeds and their products]. AB - The composition, some physical properties (density, refraction index, and color), antioxidant capacity (DPPH), and fatty acid profile of seeds of black (Brassica nigra) or yellow mustard (Brassica alba) were evaluated, as well as for their oils and residues from oil extraction. Density of the black and yellow mustard oils were 0.912 +/- 0.01 and 0.916 +/- 0.01 g/mL, respectively; their refraction indexes were 1.4611 +/- 0.01 and 1.4617 +/- 0.01, respectively; being not significantly different (p > 0.05) between two mustards. Color parameters of the black and yellow mustard oils presented greenish-yellow tones and reddish-yellow tones, respectively; regarding antioxidant activities, these ranged from 25 mg equivalents of Trolox/100 gin the yellow mustard oil to 1,366 mg equivalents of Trolox/100 g in the residues from oil extraction of black seed mustard. The fatty acid profile of the black mustard seed revealed that its predomipant fatty acid is oleic (22.96%), followed by linoleic (6.63%) and linolenic (3.22%), whereas foryellow mustard seed the major fatty acid is erucic (6.87%), followed by oleic (5.08%) and linoleic (1.87%) acids. PMID- 26817386 TI - [Ricardo Bressani Castignoli, Ph.D. (1926-2015)]. PMID- 26817387 TI - [Ivan Beghin (1932-2015)]. PMID- 26817388 TI - Response to letter to the editor re 'Renal tract abnormalities missed in a historical cohort of young children with UTI if the NICE and AAP imaging guidelines were applied'. PMID- 26817389 TI - Commentary to "Use of human acellular dermal matrix during classic bladder exstrophy repair". PMID- 26817390 TI - Endoscopic treatment of recurrent tracheoesophageal fistula with a combination of N-butyl-2-cyanocrylate (Histoacryl(r)) and lipiodol via esophagoscopy in a pediatric patient. PMID- 26817391 TI - Letter in response to "MDMA-induced angioedema treated with icatibant". PMID- 26817392 TI - Consumption of fruits and vegetables among adolescents: a multi-national comparison of eleven countries in the Eastern Mediterranean Region. AB - Regional cross-country profile of fruit and vegetable (F&V) consumption is lacking in the Eastern Mediterranean Region (EMR). This study examines the prevalence and differences of consuming F&V >=5 times/d among adolescents in eleven EMR countries, and also describes differences in the proportions of taking F&V >=5 times/d by sex, age and BMI. The study included 26 328 school adolescents (13-15 years) with complete data on consumption of F&V, age, sex, weight and height taken from the Global School-based Student Health Survey conducted in the EMR between 2005 and 2009. Overall, only 19.4 % of adolescents reported consuming F&V >=5 times/d. The highest prevalence was reported in Djibouti (40.4 %) and the lowest was reported in Pakistan (10.0 %). Statistically significant differences in prevalence were observed across countries (P<0.05). With the exception of Oman, Libya and Djibouti, significantly more males than females ate F&V >=5 times/d. Proportion of students consuming F&V >=5 times/d also varied significantly in all counties based on BMI (P<0.0001), with students within normal BMI having the highest frequency. A negative trend was observed between age and the prevalence of taking F&V >=5 times/d in most of the eleven EMR countries but Jordan, Djibouti and Morocco. The prevalence of adequate intake of F&V was low in the eleven EMR countries. There is a need for interventions to increase the prevalence of adolescents consuming F&V >=5 times/d. Interventions should take into consideration psychosocial, environmental and socio environmental factors influencing F&V intake within countries. PMID- 26817393 TI - Effects of porous media, macrophyte type and hydraulic retention time on the removal of organic load and micropollutants in constructed wetlands. AB - The performance of horizontal subsurface flow constructed wetlands in the removal of micropollutants from a wastewater treatment plant effluent was evaluated at mesocosm level. Fifteen mesocosms were studied following a modified Latin Square experimental design with six additional points. Three variables at three levels were studied: porous media -PM- (river gravel, fine volcanic gravel and coarse volcanic gravel), macrophyte type -M- (Thypa latiffolia, Phragmites australis, and Cyperus papyrus) and hydraulic retention time -HRT- (1, 3 and 5 days). As response variables the removal percentages of the total organic load of the effluent (BOD5) and the loads of several micropollutants (caffeine, galaxolide, tonalide, alkylphenols and their monoethoxylates and diethoxylates, methyl dihydrojasmonate, sunscreen UV-15 and parsol) were used. The results showed that the systems remove between 70% and 75% of the organic load and that all the micropollutants were degraded at different extents, from 55% to 99%. The HRT was the variable that showed major effects on the treatment process, while M and PM showed no statistically significant differences in the used experimental conditions. PMID- 26817394 TI - Isomerism in Au28(SR)20 Nanocluster and Stable Structures. AB - Understanding the isomerism phenomenon at the nanoscale is a challenging task because of the prerequisites of precise composition and structural information on nanoparticles. Herein, we report the ligand-induced, thermally reversible isomerization between two thiolate-protected 28-gold-atom nanoclusters, i.e. Au28(S-c-C6H11)20 (where -c-C6H11 = cyclohexyl) and Au28(SPh-(t)Bu)20 (where -Ph (t)Bu = 4-tert-butylphenyl). The intriguing ligand effect in dictating the stability of the two Au28(SR)20 structures is further investigated via dispersion corrected density functional theory calculations. PMID- 26817395 TI - Cytokines of the LIF/CNTF family and metabolism. AB - The incidence of obesity is increasing worldwide. Obesity is accompanied by a chronic inflammatory state that increases the risk of metabolic diseases such as insulin-resistance and type 2 diabetes. Over the past two decades, interest in immunomodulatory cytokines as potential mediators and/or targets for treatment or prevention of obesity and metabolic syndrome has increased. In this review, we summarize studies that revealed the effects of LIF family cytokines on adipose tissue, energy expenditure and food intake, highlighting the importance of gp130/LIFRbeta signaling in obesity and obesity-related metabolic diseases. PMID- 26817396 TI - p27kip1 overexpression regulates IL-1beta in the microenvironment of stem cells and eutopic endometriosis co-cultures. AB - Endometriosis is a gynecological benign chronic disease defined as the growth of endometrial glands and stroma in extra-uterine sites, most commonly implanted over visceral and peritoneal surfaces within the female pelvis causing inflammatory lesions. It affects around 10% of the female population and is often accompanied by chronic pelvic pain, adhesion formation and infertility. Therefore, endometriosis could be considered a "social disease", since it affects the quality of life, reproductivity and also has a socio-economic impact. The expression of cell cycle and inflammatory proteins is modified in the endometriotic tissues. Immunostaining of glandular and stromal cells in endometrial biopsies obtained from patients with endometriosis compared with those of healthy control demonstrated that endometriotic tissues have lower levels of p27kip1 protein. Endometriosis endometrial cells cultures have also lower levels of p27kip1 compared to health endometrial cells cultures and restore the cell cycle balance when transduced with an adenoviral vector carring the p27kip1 coding gene (Adp27EGFP). The low levels of p27kip1 are related to the S phase in the cell cycle, whereas higher levels lead to a G1 cell cycle arrest. The inflammatory cytokine IL-1beta was recently identified as another key protein in the endometriosis proliferation. This cytokine has elevated levels during the proliferative and secretory phases of the menstrual cycle. In endometriosis endometrial cells cultures the IL-1beta stimulates the production of IL-6 and IL 8, increasing the cell proliferation and reducing the apoptosis and Bax expression in these cells. According to these remarks, this work aims to evaluate the inflammatory effects in vitro, but more next to what happens in a woman's body, associating endometrial cells with stem cells, thus mimicking the endometrial microenvironment, with gene therapy using Adp27, notoriously known as controller cell cycle, apoptosis and potent modulator of VEGF expression. PMID- 26817397 TI - TC-PTP and PTP1B: Regulating JAK-STAT signaling, controlling lymphoid malignancies. AB - Lymphoid malignancies are characterized by an accumulation of genetic lesions that act co-operatively to perturb signaling pathways and alter gene expression programs. The Janus kinases (JAK)-signal transducers and activators of transcription (STATs) pathway is one such pathway that is frequently mutated in leukemia and lymphoma. In response to cytokines and growth factors, a cascade of reversible tyrosine phosphorylation events propagates the JAK-STAT pathway from the cell surface to the nucleus. Activated STAT family members then play a fundamental role in establishing the transcriptional landscape of the cell. In leukemia and lymphoma, somatic mutations have been identified in JAK and STAT family members, as well as, negative regulators of the pathway. Most recently, inactivating mutations in the protein tyrosine phosphatase (PTP) genes PTPN1 (PTP1B) and PTPN2 (TC-PTP) were sequenced in B cell lymphoma and T cell acute lymphoblastic leukemia (T-ALL) respectively. The loss of PTP1B and TC-PTP phosphatase activity is associated with an increase in cytokine sensitivity, elevated JAK-STAT signaling, and changes in gene expression. As inactivation mutations in PTPN1 and PTPN2 are restricted to distinct subsets of leukemia and lymphoma, a future challenge will be to identify in which cellular contexts do they contributing to the initiation or maintenance of leukemogenesis or lymphomagenesis. As well, the molecular mechanisms by which PTP1B and TC-PTP loss co-operates with other genetic aberrations will need to be elucidated to design more effective therapeutic strategies. PMID- 26817398 TI - 3D-printing and the effect on medical costs: a new era? AB - 3D-printing (3DP) is the art and science of printing in a new dimension using 3D printers to transform 3D computer aided designs (CAD) into life-changing products. This includes the design of more effective and patient-friendly pharmaceutical products as well as bio-inspired medical devices. It is poised as the next technology revolution for the pharmaceutical and medical-device industries. After decorous implementation scientists in collaboration with CAD designers have produced innovative medical devices ranging from pharmaceutical tablets to surgical transplants of the human face and skull, spinal implants, prosthetics, human organs and other biomaterials. While 3DP may be cost efficient, a limitation exists in the availability of 3D printable biomaterials for most applications. In addition, the loss of skilled labor in producing medical devices such as prosthetics and other devices may affect developing economies. This review objectively explores the potential growth and impact of 3DP costs in the medical industry. PMID- 26817399 TI - Deficits in low beta desynchronization reflect impaired emotional processing in schizophrenia. AB - Empirical data from previous investigations showed that emotion processing is reflected in beta, and especially in low beta event related desynchronization (ERD) (i.e. a decrease in low beta power). While recognition of social information and emotion processing are impaired in schizophrenia, no previous study analyzed induced and evoked beta oscillations in patients with schizophrenia during emotion processing. Twenty-eight subjects with schizophrenia and twenty-seven healthy controls subjects were enrolled in the study. The two study groups did not differ in age, gender and education. Participants viewed positive, neutral and negative scenes selected from the International Affective Picture System (IAPS) while 128-channel EEG was recorded. A significantly weaker low beta ERD was detected in patients relative to controls for the negative stimulus condition in the right parieto-occipital and temporal regions. Patients with decreased beta ERD showed more prominent negative symptoms and more severe deficits in psychosocial functioning. Only in the control group stronger beta ERD was detected for the negative stimuli relative to positive and neutral stimuli in the same regions. Our major finding is that impaired emotion processing in schizophrenia is reflected in decreased low beta ERD and in the diminished differences between low beta ERD to negative and non-negative emotional stimuli. Furthermore, it was found that patients with decreased beta ERD show more prominent negative symptoms and more severe deficits in psychosocial functioning. PMID- 26817400 TI - Exposure to conflict and disaster: A national survey on the prevalence of psychotic experiences in Sri Lanka. AB - Recent research conducted in high-income countries suggests psychotic experiences are common in the general population, but evidence from low- and middle-income countries (LMIC) remains limited. Sri Lanka is a LMIC affected by three decades of civil conflict and, in 2004, a devastating tsunami. This study aimed to investigate the prevalence of psychotic experiences in a general population sample in Sri Lanka and associations with conflict- and tsunami-related trauma. This is a first National Mental Health Survey conducted in Sri Lanka. A cross sectional, multi-stage, cluster sampling design was used to estimate the prevalence of psychotic symptoms. Data on socio-demographic characteristics, conflict- and tsunami-related trauma, and psychotic experiences were collected using culturally validated measures in a sample of 5927 participants. The weighted prevalence of psychotic symptoms was 9.7%. Exposure to one or more conflict-related events (adj. OR 1.79, 95% CI 1.40-2.31, p<0.001) and loss or injury of a family member or friend through conflict (adj. OR, 1.83, 95% CI 1.42 2.37, p<0.001) were associated with increased odds of reporting psychotic experiences. Psychotic experiences were more common in individuals directly exposed to tsunami disaster (adj. OR, 1.68, 95% CI 1.04-2.73, P=0.035) and in those who had a family member who died or was injured as result of tsunami (adj. OR, 1.42, 95% CI 1.04-1.94, p=0.029). Our findings suggest that psychotic experiences are common in the Sri Lankan population. Exposure to traumatic events in armed conflicts and natural disasters may be important socio-environmental factors in the development of psychotic experiences. PMID- 26817401 TI - Elevated striatal dopamine and efference copy failure in schizophrenia. PMID- 26817402 TI - Discriminating autism spectrum disorders from schizophrenia by investigation of mental state attribution on an on-line mentalizing task: A review and meta analysis. AB - In recent years, theories of how humans form a "theory of mind" of others ("mentalizing") have increasingly been called upon to explain impairments in social interaction in mental disorders, such as autism spectrum disorders (ASD) and schizophrenia. However, it remains unclear whether tasks that assess impairments in mentalizing can also contribute to determining differential deficits across disorders, which may be important for early identification and treatment. Paradigms that challenge mentalizing abilities in an on-line, real life fashion have been considered helpful in detecting disease-specific deficits. In this review, we are therefore summarizing results of studies that assess the attribution of mental states using an animated triangles task. Behavioral as well as brain imaging studies in ASD and schizophrenia have been taken into account. While for neuroimaging methods, data are sparse and investigation methods inconsistent, we performed a meta-analysis of behavioral data to directly investigate performance deficits across disorders. Here, more impaired abilities in the appropriate description of interactions were found in ASD patients than in patients with schizophrenia. Moreover, an analysis of first-episode (FES) versus longer lasting (LLS) schizophrenia showed that usage of mental state terms was reduced in the LLS group. In our review and meta-analysis, we identified performance differences between ASD and schizophrenia that seem helpful in targeting differential deficits, taking into account different stages of schizophrenia. However, to tackle the deficits in more detail, studies are needed that directly compare patients with ASD and schizophrenia using behavioral or neuroimaging methods with more standardized task versions. PMID- 26817403 TI - Application of multiparametric procedures for assessing the heritability of circadian health. AB - At present, the measurement of circadian system status under free-living conditions by the use of sensors is a relatively new technique. The data obtained using these methods are influenced by strong environmental masking factors and artifacts that can affect its recording. Therefore, the use of integrative variables such as TAP, a measure that includes temperature, activity and position that reduces these drawbacks and the number of parameters obtained is necessary. However, the relative genetic contribution to this circadian marker is unknown. The aim of our study was to ascertain the relative importance of genetic influences in TAP, and for each of its components using classical twin models. The study was performed in 53 pairs of female twins [28 monozygotic (MZ) and 25 dizygotic (DZ)] with mean age 52 +/- 6 years. Circadian patterns were studied by analyzing temperature, body position and activity for 1 week every 1 min with "Circadianware(r).". Genetic influences affecting the variability of each of the measurements were estimated by comparing the observed data in twin pairs. MZ twins showed higher intrapair correlations than DZ twins for most of the parameters. Genetic factors (broad sense heritability) were responsible for about 40-72% of TAP variance in parameters such as mesor, acrophase, amplitude, Rayleigh test, percentage of rhythmicity and circadian function index. We found more homogeneous heritability estimates of the circadian system when using an integrative technique such as TAP than with individual variables alone, suggesting that this measurement can be more reliable and less subject to environmental artifacts. PMID- 26817404 TI - The effect of recording site on extracted features of motor unit action potential. AB - Motor unit action potential (MUAP), which consists of individual muscle fiber action potentials (MFAPs), represents the electrical activity of the motor unit. The values of the MUAP features are changed by denervation and reinnervation in neurogenic involvement as well as muscle fiber loss with increased diameter variability in myopathic diseases. The present study is designed to investigate how increased muscle fiber diameter variability affects MUAP parameters in simulated motor units. In order to detect this variation, simulated MUAPs were calculated both at the innervation zone where the MFAPs are more synchronized, and near the tendon, where they show increased temporal dispersion. Reinnervation in neurogenic state increases MUAP amplitude for the recordings at both the innervation zone and near the tendon. However, MUAP duration and the number of peaks significantly increased in a case of myopathy for recordings near the tendon. Furthermore, of the new features, "number of peaks*spike duration" was found as the strongest indicator of MFAP dispersion in myopathy. MUAPs were also recorded from healthy participants in order to investigate the biological counterpart of the simulation data. MUAPs which were recorded near to tendon revealed significantly prolonged duration and decreased amplitude. Although the number of peaks was increased by moving the needle near to tendon, this was not significant. PMID- 26817405 TI - Methodology to automatically detect abnormal values of vital parameters in anesthesia time-series: Proposal for an adaptable algorithm. AB - Abnormal values of vital parameters such as hypotension or tachycardia may occur during anesthesia and may be detected by analyzing time-series data collected during the procedure by the Anesthesia Information Management System. When crossed with other data from the Hospital Information System, abnormal values of vital parameters have been linked with postoperative morbidity and mortality. However, methods for the automatic detection of these events are poorly documented in the literature and differ between studies, making it difficult to reproduce results. In this paper, we propose a methodology for the automatic detection of abnormal values of vital parameters. This methodology uses an algorithm allowing the configuration of threshold values for any vital parameters as well as the management of missing data. Four examples illustrate the application of the algorithm, after which it is applied to three vital signs (heart rate, SpO2, and mean arterial pressure) to all 2014 anesthetic records at our institution. PMID- 26817406 TI - Conversations about analgesics in the emergency department: A qualitative study. AB - OBJECTIVE: We sought to characterize conversations about analgesics in the Emergency Department (ED) setting. METHODS: A secondary analysis of 47 audio recorded ED visits containing conversations about analgesics was performed. Data were collected at an urban, academic medical center among adults with one of four diagnoses. Visit transcripts were analyzed qualitatively using content and constant comparative analysis. The speaker, medication being discussed, and overall conversation concordance were categorized. RESULTS: Among the 47 transcripts there were 1102 unique statements related to analgesics. Thirteen codes were identified; however, four codes (discussing details of administration, forecasting, side effects, past history) accounted for over 65% of the conversations. Patient requests, statements related to chronic pain and contentious conversations occurred infrequently, but were present (17% discordant conversations, 83% concordant). Medical providers dominated the conversations with patients' contributions equaling only a quarter of total coded conversation. CONCLUSIONS: These findings characterize the narrow range of topics discussed about analgesics and demonstrate that many risks of opioid medications were not discussed. PRACTICE IMPLICATIONS: Increased counseling about opioids may be warranted given rising opioid-related deaths. To be prepared, providers may wish to reflect on how to approach different topics related to opioids and analgesia prior to engaging in such discussions. PMID- 26817407 TI - Exploring the role of health literacy in the evaluation of online health information: Insights from a mixed-methods study. AB - OBJECTIVE: To gain new insights into the relationship between health literacy and evaluation of online health information. METHODS: Using a mixed-methods approach, forty-four semi-structured interviews were conducted followed by a short questionnaire on health literacy and eHealth literacy. Qualitative and quantitative data were merged to explore differences and similarities among respondents with different health literacy levels. RESULTS: Thematic analysis showed that most respondents did not question the quality of online health information and relied on evaluation criteria not recognized by existing web quality guidelines. Individuals with low health literacy, despite presenting higher eHealth literacy scores, appeared to use less established criteria and to rely more heavily on non-established ones compared to those with high health literacy. CONCLUSION: Disparities in evaluation ability among people with different health literacy might be related to differences in awareness of the issue and to the use of different evaluation criteria. Future research should quantitatively investigate the interplay between health literacy, use of established and non-established criteria, and ability to evaluate online health information. PRACTICE IMPLICATIONS: Communication and patient education efforts should aim to raise awareness on online health information quality and to promote use of established evaluation criteria, especially among low health literate citizens. PMID- 26817408 TI - Self-Powered Solar-Blind Photodetector with Fast Response Based on Au/beta-Ga2O3 Nanowires Array Film Schottky Junction. AB - Because of the direct band gap of 4.9 eV, beta-Ga2O3 has been considered as an ideal material for solar-blind photodetection without any bandgap tuning. Practical applications of the photodetectors require fast response speed, high signal-to-noise ratio, low energy consumption and low fabrication cost. Unfortunately, most reported beta-Ga2O3-based photodetectors usually possess a relatively long response time. In addition, the beta-Ga2O3 photodetectors based on bulk, the individual 1D nanostructure, and the film often suffer from the high cost, the low repeatability, and the relatively large dark current, respectively. In this paper, a Au/beta-Ga2O3 nanowires array film vertical Schottky photodiode is successfully fabricated by a simple thermal partial oxidation process. The device exhibits a very low dark current of 10 pA at -30 V with a sharp cutoff at 270 nm. More interestingly, the 90-10% decay time of our device is only around 64 MUs, which is much quicker than any other previously reported beta-Ga2O3-based photodetectors. Besides, the self-powering, the excellent stability and the good reproducibility of Au/beta-Ga2O3 nanowires array film photodetector are helpful to its commercialization and practical applications. PMID- 26817409 TI - Income, neural executive processes, and preschool children's executive control. AB - This study aimed to specify the neural mechanisms underlying the link between low household income and diminished executive control in the preschool period. Specifically, we examined whether individual differences in the neural processes associated with executive attention and inhibitory control accounted for income differences observed in performance on a neuropsychological battery of executive control tasks. The study utilized a sample of preschool-aged children (N = 118) whose families represented the full range of income, with 32% of families at/near poverty, 32% lower income, and 36% middle to upper income. Children completed a neuropsychological battery of executive control tasks and then completed two computerized executive control tasks while EEG data were collected. We predicted that differences in the event-related potential (ERP) correlates of executive attention and inhibitory control would account for income differences observed on the executive control battery. Income and ERP measures were related to performance on the executive control battery. However, income was unrelated to ERP measures. The findings suggest that income differences observed in executive control during the preschool period might relate to processes other than executive attention and inhibitory control. PMID- 26817410 TI - Osseointegrated implants for orbito-facial prostheses: Preoperative planning tips and intraoperative pearls. AB - PURPOSE: Implant-retained facial prostheses are becoming increasingly sophisticated. We describe our experience with successful implant placement. METHODS: Retrospective case series. Patients with severe unilateral orbital deformity who underwent socket reconstruction with placement of orbital implants were identified. Data on patient age, gender, mechanism of eye, soft tissue, and bone loss, prior reconstructive surgeries and radiation, and orbital imaging were collected and analyzed. RESULTS: Four patients (9 implants) between 2010 and 2014, who had osseointegrated implants placed for orbito-facial prostheses were identified. Three were male, one female. Average age was 59 years (range 34-86). Reason for eye loss was trauma in two patients, exenteration for recurrent rhabdomyosarcoma in one patient, and enucleation for retinoblastoma in one patient. All patients had Vistafix(r) (Gothenburg, Sweden) osseointegrated titanium implants (4 mm) placed in a 2-stage procedure over a span of 3-6 months with subsequent successful prosthesis fitting. CONCLUSION: Implant-retained orbito-facial prostheses are safe, easy, and reliable. The ideal socket has minimal dead space, robust bone, and soft tissue 4-5 mm in depth. Preoperative planning should consist of: 1) orbit CT; 2) careful clinical exam of the orbital deformity; and, 3) analysis of socket topography. Operative tips for successful implant placement include: 1) 2-3 points of fixation; 2) placement of implants in bone of adequate thickness; and 3) implant placement as a 2-stage rather than 1 stage procedure. There appears to be no difference in outcome in irradiated and non-irradiated sockets in this series, but should be a consideration and discussed with the patient. PMID- 26817411 TI - Wind-blown Sand Electrification Inspired Triboelectric Energy Harvesting Based on Homogeneous Inorganic Materials Contact: A Theoretical Study and Prediction. AB - Triboelectric nanogenerator (TENG) based on contact electrification between heterogeneous materials has been widely studied. Inspired from wind-blown sand electrification, we design a novel kind of TENG based on size dependent electrification using homogeneous inorganic materials. Based on the asymmetric contact theory between homogeneous material surfaces, a calculation of surface charge density has been carried out. Furthermore, the theoretical output of homogeneous material based TENG has been simulated. Therefore, this work may pave the way of fabricating TENG without the limitation of static sequence. PMID- 26817412 TI - Analgesic Effect of Recombinant GABAergic Cells in a Model of Peripheral Neuropathic Pain. AB - Chronic neuropathic pain represents a clinically challenging state with a poor response to current treatment options. Long-term management of chronic pain is often associated with the development of tolerance, addiction, and other side effects, reducing the therapeutic value of treatment. Alternative strategies based on cell therapy and gene manipulation, balancing the inhibitory and excitatory events in the spinal cord, may provide sustained pain relief in the long term. Transplantation of GABAergic cells has been successfully used to enhance inhibition and to restore physiological spinal pain processing. However, since the underlying mechanism of chronic pain development involves changes in several pain-signaling pathways, it is essential to develop an approach that targets several components of pain signaling. Recombinant cell therapy offers the possibility to deliver additional analgesic substances to the restricted area in the nervous system. The current study explores the analgesic potential of genetically modified rat embryonic GABAergic cells releasing a peptidergic NMDA receptor antagonist, Serine(1)-histogranin (SHG). Overactivation of glutamate NMDA receptors contributes to the hyperexcitability of spinal neurons observed in chronic pain models. Our approach allows us to simultaneously target spinal hyperexcitability and reduced inhibitory processes. Transplantable cells were transduced by viral vectors encoding either one or six copies of SHG cDNAs. The analgesic potential of recombinant cells after their intraspinal transplantation was evaluated in a model of peripheral nerve injury. Enhanced reduction of hypersensitivity to thermal and mechanical stimuli was observed in animals treated by recombinant cells compared to the nonrecombinant group. The recombinant peptide was detected in the spinal tissue, suggesting its successful production by transplanted cells. Our results demonstrate the feasibility of using recombinant cells releasing adjunct analgesic peptides in the therapy of neuropathic pain. PMID- 26817413 TI - Epicardial adipose tissue volume but not density is an independent predictor for myocardial ischemia. AB - BACKGROUND: Epicardial adipose tissue (EAT) volume is associated with plaque formation and cardiovascular event risk, its density may reflect tissue composition and metabolic activity. OBJECTIVES: Global and regional associations between EAT volume and density, ischemia and coronary calcium were investigated using a novel automatic quantitative measurement software. METHODS: 71 patients with an intermediate pre-test probability for coronary artery disease and inducible ischemia by SPECT were matched to two same-gender controls (total of 213 patients, 90% male, age 60 +/- 10 years). Non-contrast CT for assessment of EAT volume, density (in Hounsfield Unit [HU]) and coronary calcium score (CCS) was performed. RESULTS: Global EAT volume was significantly increased in ischemic patients compared to controls (96 +/- 49 vs. 82 +/- 36 cm(3), p = 0.04), density showed no significant difference (-75.6 +/- 4.3 vs. -75.1 +/- 4.1HU, p = 0.63). EAT volume and density differed significantly between coronary territories (LAD: 37 +/- 18 cm(3), -77.8 +/- 4.5HU; LCx: 16 +/- 9 cm(3), -73.9 +/- 4.1HU; RCA: 36 +/- 17 cm(3), -71.7 +/- 4.8HU, p < 0.001). For regional ischemia, only LCx territory showed a significantly higher EAT volume (18 +/- 8 vs. 16 +/- 9 cm(3), p = 0.048). Multivariable logistic regression revealed a significant association with ischemia for EAT volume (OR 2.09 (1.0; 4.3), p = 0.049) and CCS (OR 1.43 (1.1; 1.9), p = 0.006). EAT volume significantly improved discrimination of ischemia over CCS (Integrated Discrimination Improvement: 3.5%, 95%CI: 1.1-6.1%, p = 0.004). Hypertension was the only risk factor significantly influencing EAT volume and density (98 +/- 48 vs. 78 +/- 31 cm(3), p = 0.002, -76.0 +/- 4.1 vs. 74.5 +/- 4.1 HU, p = 0.01). CONCLUSIONS: EAT volume is associated with myocardial ischemia and improves the discriminative power for independent ischemia prediction over CCS. In hypertensive patients, EAT is characterized by lower density and higher volumes. PMID- 26817414 TI - Total coronary atherosclerotic plaque burden assessment by CT angiography for detecting obstructive coronary artery disease associated with myocardial perfusion abnormalities. AB - BACKGROUND: Total atherosclerotic plaque burden assessment by CT angiography (CTA) is a promising tool for diagnosis and prognosis of coronary artery disease (CAD) but its validation is restricted to small clinical studies. We tested the feasibility of semi-automatically derived coronary atheroma burden assessment for identifying patients with hemodynamically significant CAD in a large cohort of patients with heterogenous characteristics. METHODS: This study focused on the CTA component of the CORE320 study population. A semi-automated contour detection algorithm quantified total coronary atheroma volume defined as the difference between vessel and lumen volume. Percent atheroma volume (PAV = [total atheroma volume/total vessel volume] * 100) was the primary metric for assessment (n = 374). The area under the receiver operating characteristic curve (AUC) determined the diagnostic accuracy for identifying patients with hemodynamically significant CAD defined as >=50% stenosis by quantitative coronary angiography and associated myocardial perfusion abnormality by SPECT. RESULTS: Of 374 patients, 139 (37%) had hemodynamically significant CAD. The AUC for PAV was 0.78 (95% confidence interval [CI] 0.73-0.83) compared with 0.84 [0.79-0.88] by standard expert CTA interpretation (p = 0.02). Accuracy for both CTA (0.91 [0.87, 0.96]) and PAV (0.86 [0.81-0.91]) increased after excluding patients with history of CAD (p < 0.01 for both). Bland-Altman analysis revealed good agreement between two observers (bias of 280.2 mm(3) [161.8, 398.7]). CONCLUSIONS: A semi-automatically derived index of total coronary atheroma volume yields good accuracy for identifying patients with hemodynamically significant CAD, though marginally inferior to CTA expert reading. These results convey promise for rapid, reliable evaluation of clinically relevant CAD. PMID- 26817415 TI - A non-inheritable maternal Cas9-based multiple-gene editing system in mice. AB - The CRISPR/Cas9 system is capable of editing multiple genes through one-step zygote injection. The preexisting method is largely based on the co-injection of Cas9 DNA (or mRNA) and guide RNAs (gRNAs); however, it is unclear how many genes can be simultaneously edited by this method, and a reliable means to generate transgenic (Tg) animals with multiple gene editing has yet to be developed. Here, we employed non-inheritable maternal Cas9 (maCas9) protein derived from Tg mice with systemic Cas9 overexpression (Cas9 mice). The maCas9 protein in zygotes derived from mating or in vitro fertilization of Tg/+ oocytes and +/+ sperm could successfully edit the target genome. The efficiency of such maCas9-based genome editing was comparable to that of zygote microinjection-based genome editing widely used at present. Furthermore, we demonstrated a novel approach to create "Cas9 transgene-free" gene-modified mice using non-Tg (+/+) zygotes carrying maCas9. The maCas9 protein in mouse zygotes edited nine target loci simultaneously after injection with nine different gRNAs alone. Cas9 mouse derived zygotes have the potential to facilitate the creation of genetically modified animals carrying the Cas9 transgene, enabling repeatable genome engineering and the production of Cas9 transgene-free mice. PMID- 26817416 TI - Volta phase plate cryo-EM of the small protein complex Prx3. AB - Cryo-EM of large, macromolecular assemblies has seen a significant increase in the numbers of high-resolution structures since the arrival of direct electron detectors. However, sub-nanometre resolution cryo-EM structures are rare compared with crystal structure depositions, particularly for relatively small particles (<400 kDa). Here we demonstrate the benefits of Volta phase plates for single particle analysis by time-efficient cryo-EM structure determination of 257 kDa human peroxiredoxin-3 dodecamers at 4.4 A resolution. The Volta phase plate improves the applicability of cryo-EM for small molecules and accelerates structure determination. PMID- 26817417 TI - Random genetic drift, natural selection, and noise in human cranial evolution. AB - OBJECTIVES: This study assesses the extent to which relationships among groups complicate comparative studies of adaptation in recent human cranial variation and the extent to which departures from neutral additive models of evolution hinder the reconstruction of population relationships among groups using cranial morphology. MATERIALS AND METHODS: Using a maximum likelihood evolutionary model fitting approach and a mixed population genomic and cranial data set, I evaluate the relative fits of several widely used models of human cranial evolution. Moreover, I compare the goodness of fit of models of cranial evolution constrained by genomic variation to test hypotheses about population specific departures from neutrality. RESULTS: Models from population genomics are much better fits to cranial variation than are traditional models from comparative human biology. There is not enough evolutionary information in the cranium to reconstruct much of recent human evolution but the influence of population history on cranial variation is strong enough to cause comparative studies of adaptation serious difficulties. Deviations from a model of random genetic drift along a tree-like population history show the importance of environmental effects, gene flow, and/or natural selection on human cranial variation. Moreover, there is a strong signal of the effect of natural selection or an environmental factor on a group of humans from Siberia. DISCUSSION: The evolution of the human cranium is complex and no one evolutionary process has prevailed at the expense of all others. A holistic unification of phenome, genome, and environmental context, gives us a strong point of purchase on these problems, which is unavailable to any one traditional approach alone. Am J Phys Anthropol 160:582-592, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26817418 TI - Tunable exchange bias in dilute magnetic alloys - chiral spin glasses. AB - A unidirectional anisotropy appears in field cooled samples of dilute magnetic alloys at temperatures well below the cusp temperature of the zero field cooled magnetization curve. Magnetization measurements on a Cu(13.5 at% Mn) sample show that this anisotropy is essentially temperature independent and acts on a temperature dependent excess magnetization, DeltaM. The anisotropy can be partially or fully transferred from being locked to the direction of the cooling field at lower fields to becoming locked to the direction of DeltaM at larger fields, thus instead appearing as a uniaxial anisotropy. This introduces a deceiving division of the anisotropy into a superposition of a unidirectional and a uniaxial part. This two faced nature of the anisotropy has been empirically scrutinized and concluded to originate from one and the same exchange mechanism: the Dzyaloshinsky-Moriya interaction. PMID- 26817419 TI - Phonon transport at the interfaces of vertically stacked graphene and hexagonal boron nitride heterostructures. AB - Hexagonal boron nitride (h-BN) is a promising substrate for graphene based nano electronic devices. We investigate the ballistic phonon transport at the interface of vertically stacked graphene and h-BN heterostructures using first principles density functional theory and atomistic Green's function simulations considering the influence of lattice stacking. We compute the frequency and wave vector dependent transmission function and observe distinct stacking-dependent phonon transmission features for the h-BN/graphene/h-BN sandwiched systems. We find that the in-plane acoustic modes have the dominant contributions to the phonon transmission and thermal boundary conductance (TBC) for the interfaces with the carbon atom located directly on top of the boron atom (C-B matched) because of low interfacial spacing. The low interfacial spacing is a consequence of the differences in the effective atomic volume of N and B and the difference in the local electron density around N and B. For the structures with the carbon atom directly on top of the nitrogen atom (C-N matched), the spatial distance increases and the contribution of in-plane modes to the TBC decreases leading to higher contributions by out-of-plane acoustic modes. We find that the C-B matched interfaces have stronger phonon-phonon coupling than the C-N matched interfaces, which results in significantly higher TBC (more than 50%) in the C-B matched interface. The findings in this study will provide insights to understand the mechanism of phonon transport at h-BN/graphene/h-BN interfaces, to better explain the experimental observations and to engineer these interfaces to enhance heat dissipation in graphene based electronic devices. PMID- 26817420 TI - The effects of hemoglobin levels and their interactions with cigarette smoking on survival in nasopharyngeal carcinoma patients. AB - There is very little published information regarding the prognostic value of hemoglobin (Hb) levels combined with smoking on the survival of patients with nasopharyngeal carcinoma (NPC), and the interactions between them remain unclear. A total of 2440 NPC patients were confirmed, and multivariate analysis was performed to identify valuable prognostic Hb levels in the entire population and in the cohort of smokers. The survival differences were compared using log-rank tests. The multiplicative and additive interactions were assessed using Cox regression and a Microsoft Word Excel spreadsheet. Postradiotherapy (RT) Hb was an independent prognostic factor for overall survival (OS) (HR = 0.797; P = 0.006), failure-free survival (FFS) (HR=0.811; P = 0.010), and loco-regional failure-free survival (LR-FFS) (HR = 0.725; P = 0.000). In the cohort of smokers, pack-years was also an independent predictor of OS (HR = 0.673; P < 0.001) and FFS (HR = 0.681; P < 0.001), LR-FFS (HR = 0.663; P = 0.001). A significant positive additive effect was found for the interaction between low post-RT Hb and high SI on OS, with RERI = 5.616, AP = 0.665, and S = 4.078. Stratified analyses demonstrated that heavy smokers with low post-RT Hb had HRs of 2.295 (P < 0.001) for death, 2.222 (P < 0.001) for disease failure, and 2.267 (P < 0.001) loco regional recurrence compared with light smokers with high post-RT Hb levels, and post-RT Hb level is an important predictor of survival in patients with NPC. The positive interaction between post-RT Hb level and pack-years contributes to the elevated risk of poor survival. Oncologists should devote particular attention to heavy smokers with low post-RT Hb levels in the future. PMID- 26817421 TI - Identification of miRNA-mRNA regulatory modules by exploring collective group relationships. AB - BACKGROUND: microRNAs (miRNAs) play an essential role in the post-transcriptional gene regulation in plants and animals. They regulate a wide range of biological processes by targeting messenger RNAs (mRNAs). Evidence suggests that miRNAs and mRNAs interact collectively in gene regulatory networks. The collective relationships between groups of miRNAs and groups of mRNAs may be more readily interpreted than those between individual miRNAs and mRNAs, and thus are useful for gaining insight into gene regulation and cell functions. Several computational approaches have been developed to discover miRNA-mRNA regulatory modules (MMRMs) with a common aim to elucidate miRNA-mRNA regulatory relationships. However, most existing methods do not consider the collective relationships between a group of miRNAs and the group of targeted mRNAs in the process of discovering MMRMs. Our aim is to develop a framework to discover MMRMs and reveal miRNA-mRNA regulatory relationships from the heterogeneous expression data based on the collective relationships. RESULTS: We propose DIscovering COllective group RElationships (DICORE), an effective computational framework for revealing miRNA-mRNA regulatory relationships. We utilize the notation of collective group relationships to build the computational framework. The method computes the collaboration scores of the miRNAs and mRNAs on the basis of their interactions with mRNAs and miRNAs, respectively. Then it determines the groups of miRNAs and groups of mRNAs separately based on their respective collaboration scores. Next, it calculates the strength of the collective relationship between each pair of miRNA group and mRNA group using canonical correlation analysis, and the group pairs with significant canonical correlations are considered as the MMRMs. We applied this method to three gene expression datasets, and validated the computational discoveries. CONCLUSIONS: Analysis of the results demonstrates that a large portion of the regulatory relationships discovered by DICORE is consistent with the experimentally confirmed databases. Furthermore, it is observed that the top mRNAs that are regulated by the miRNAs in the identified MMRMs are highly relevant to the biological conditions of the given datasets. It is also shown that the MMRMs identified by DICORE are more biologically significant and functionally enriched. PMID- 26817422 TI - Mechanism of leaf-cutting ant colony suppression by fipronil used in attractive toxic baits. AB - BACKGROUND: Attractive toxic baits are the prevailing method for managing leaf cutting ants in the eucalypt forests planted for the production of pulp, paper, timber and charcoal. For successful use in these baits, the insecticidal compounds need to circumvent the typical defences of the eusocial leaf-cutting ants. The challenge is to have an insecticide in the bait that will not directly harm and/or compromise foraging workers, but that will eventually suppress the colony. These underlying mechanisms are poorly known, and here the potential mechanism of fipronil activity in toxic baits for leaf-cutting ants was assessed using colonies of the representative Neotropical Acromyrmex subterraneus subterraneus (Forel, 1893). RESULTS: Although forager activity was not directly impaired by fipronil, the insecticide affected forager nestmate interactions (auto- and allogrooming) and waste removal and, more importantly, greatly affected the minor workers, impairing their activities of fungus garden cultivation and progeny handling. The fast decay of the fungus garden compromised the sustainability of the colonies, ultimately leading to their demise within 8 days. CONCLUSION: The behavioural effects of sublethal insecticide exposure towards minor workers are the main determinants of insecticide activity as ant baits and should be targeted in developing such compounds. (c) 2016 Society of Chemical Industry. PMID- 26817423 TI - Low threshold photonic crystal laser based on a Rhodamine dye doped high gain polymer. AB - We demonstrate low threshold lasing oscillation in a photonic crystal (PhC) laser by using tert-butyl Rhodamine B (t-Bu-RhB) doped gain media. Lactonic t-Bu-RhB is synthesized to improve doping concentration in polymethylmethacrylate (PMMA) films, and then isomerized to the zwitterion form to achieve highly fluorescent gain medium. The t-Bu-RhB doped PMMA film is sandwiched by a pair of polystyrene colloidal crystals to construct a PhC resonating cavity. Single-mode laser oscillation at 592 nm is observed when the PhC resonating cavity is pumped by a Nd:YAG laser. The lasing threshold is 0.12 MW cm(-2) utilizing 6.9 wt% t-Bu-RhB doped PMMA films, which is only 1/60 of that with 3 wt% t-Bu-RhB doped PMMA films. The concentration-dependent lasing action is attributed to different gain factors of the t-Bu-RhB doped PMMA films. Furthermore, a spatially and spectrally coherent laser beam from the PhC resonating cavity is verified by exploring the far-field image and angular dependence of the lasing emission. The approach provides a facile and efficient strategy to reduce the lasing threshold for fabricating low threshold PhC lasers. PMID- 26817424 TI - What Is a Clinical Nurse Specialist and Why Do You Need One? PMID- 26817425 TI - Suicidality Risk Assessment in Adolescents and Young Adults. AB - The Research to Practice column is intended to improve the research critique skills of the advanced practice registered nurse (APRN) and the emergency nurse (RN) and to assist with the translation of research into practice. This column focuses on assessing risks of suicide in adolescents and young adults, using as a basis for the discussion a recently developed suicidality screening tool (L. M. ). PMID- 26817426 TI - Scapholunate Dissociation. AB - Wrist injuries are a common complaint in the emergency setting. Any disruption of the anatomy of the carpal bones can impair hand function, leading to pain, weakness, and complications. One of the most common forms of carpal bone instability is scapholunate dissociation. This injury can lead to significant morbidity including avascular necrosis, impaired healing, limited function, and arthritis. These diagnostic findings may be subtle, thus identifying high-risk mechanisms of injury, and clinical manifestations will assist the emergency practitioner with early diagnosis and treatment of this high-risk injury. PMID- 26817427 TI - Emergency Management of Malignancy-Associated Hypercalcemia. AB - The most common cause of hypercalcemia in the emergency department (ED) is malignancy-associated hypercalcemia (MAH), which can be caused by direct bone resorption from bone metastases, vitamin D secreting malignancies, and increased parathyroid hormone (PTH) or PTH-related protein (PTHrP) levels. Malignancy associated hypercalcemia is associated with a very poor prognosis, with half of the patients dying within a month of diagnosis. Management consists of adequate hydration, bisphosphonate therapy, and correction of other abnormal electrolyte levels. Currently, no therapies have demonstrated an effect on mortality and are therefore viewed only as a means of stabilizing the patient until the underlying condition can be treated. All MAH patients should receive an oncology consult as soon as possible so they are able to receive treatment for the causative malignancy and increase their chance of survival. PMID- 26817428 TI - Thyrotoxic Periodic Paralysis: A Puzzling Case of Chest Pain and Weakness. AB - Thyrotoxic periodic paralysis is an uncommon thyroid emergency that is associated with electrolyte disturbances and a progressive flaccid paralysis of lower and upper extremities. Although not typically diagnosed within the emergency department setting, advanced practice registered nurses may be key in identifying this unusual condition where rapid and appropriate treatment precipitated by hyperthyroidism, most commonly resulting from Graves' disease can mitigate adverse cardiac, renal, and neurologic sequelae. PMID- 26817429 TI - Evaluation of Physicians' and Nurses' Knowledge, Attitudes, and Compliance With Family Presence During Resuscitation in an Emergency Department Setting After an Educational Intervention. AB - Family presence during resuscitation (FPDR) has been an ongoing topic of discussion in many hospital emergency departments throughout the United States. With the current emphasis promoting patient- and family-centered care, families are now exercising their right to be present at the bedside during resuscitation. With or without a policy, there is continued resistance to allow families to remain with their loved ones during resuscitation. The purpose of this study was to evaluate if an evidence-based educational intervention would increase physicians' and nurses' knowledge, attitudes, and compliance with allowing FPDR. This quasi-experimental study evaluated 30 attending physicians' and 65 registered nurses' knowledge of an existing family presence policy and their attitudes toward family presence post-educational intervention in an emergency department setting. Compliance of family presence was observed for 2 months pre- and post-educational intervention. Results show that most physicians and nurses either were not sure or were not aware that there was an existing written policy. The study demonstrated that nurses agree more than physicians that the option of FPDR is a patient/family right. The results also showed that the educational intervention had no effect on the physicians and nurses attitudes for FPDR, but it did change behaviors. Of the events involving professionals who were exposed to the educational intervention, family members were present 87.5% of the time. In contrast, only 23% of the events involving professionals who did not receive the educational intervention had families present. Ongoing staff education will heighten awareness to FPDR, make the staff more comfortable with families being present, and will presumably continue to increase invitations for FPDR. PMID- 26817430 TI - Nurse Practitioners in the Emergency Department: Barriers and Facilitators for Role Implementation. AB - Emergency department (ED) wait times, length of stay, and overcrowding are common issues in developed health care systems in many countries. These ED issues are multifactorial in nature and require further evaluation in an attempt to provide consistent, adequate health care to each patient. Authors in countries, such as Australia and the United Kingdom, have attempted to address the concerns of increasing wait times, length of stay, and overcrowding by establishing nurse practitioners (NPs) into the ED who practice in domains traditionally dominated by physicians. Unfortunately, Canadian health care system leaders lack experience in implementing the unique role of the NP in the ED. In addition, emergency department fast track (FT) models have been studied and operationalized in Australia and the United States to streamline care for less acute patients. However, it is evident from review of the literature that NPs, in the Canadian health care system, are underutilized within FT units. Despite the fact that NPs have been practicing since the 1960s, there remains confusion by the public and even health care professionals about their role, scope of practice, and capabilities. The purpose of this article is to provide a greater understanding of the NP role in Canada with the intent to elucidate current barriers and facilitators to having NPs practice in the ED setting through appraisal of national and international literature sources. The article also illustrates how FT units streamline patient care and are suitable areas for NP practice within the ED. In addition, the authors describe how assessment, implementation, and evaluation of the role of NPs in the ED might be facilitated through the use of a Participatory Evidence-informed Patient-focused Process for Advanced practice nursing role development, implementation, and evaluation (PEPPA framework). PMID- 26817431 TI - Disaster Preparedness in the Emergency Department Using In Situ Simulation. AB - High influxes of patients during disasters have led to increased incidence of medical errors in emergency departments (EDs), ultimately leading to poor patient outcomes. Nearly 30% of errors committed in EDs are due to deficiencies in knowledge and skills, and between 60% and 70% of errors occur due in part from communication breakdowns. The goal of this project was to examine whether in situ simulation will increase health care providers' knowledge of how to perform during a disaster, improve competency in skills related to those actions, and to improve communication regarding the special circumstances inherent to a disaster in the ED. A mixed-methods pilot project analyzed the effects of in situ simulation. Results of the project demonstrate that in situ simulation can improve knowledge and communication during a disaster situation. PMID- 26817432 TI - Avoid Ethical Misconduct in Manuscript Preparation. AB - In order for nurses and other health care professionals to make important contributions to the literature, there must be an awareness of the many areas where unintentional ethical conflicts can arise. Leading ethical concerns include plagiarism, duplicate submission, authorship standards, bias, and conflicts of interest. Although many sources are available on the variety of ethical concerns, this article takes the position to identify the area of concern and describe why it is an ethical violation. Solutions are posed for resolving the conflict, including why medical librarians can help in the publishing process. PMID- 26817434 TI - Estimating the minimum control count of random network models. AB - The study of controllability of complex networks has introduced the minimum number of controls required for full controllability as a new network measure of interest. This network measure, like many others, is non-trivial to compute. As a result, establishing the significance of minimum control counts (MCCs) in real networks using random network null models is expensive. Here we derive analytic estimates for the expected MCCs of networks drawn from three commonly-used random network models. Our estimates show good agreement with exact control counts. Furthermore, the analytic expressions we derive offer insights into the structures within each random network model that induce the need for controls. PMID- 26817435 TI - Object Specific Trajectory Optimization for Industrial X-ray Computed Tomography. AB - In industrial settings, X-ray computed tomography scans are a common tool for inspection of objects. Often the object can not be imaged using standard circular or helical trajectories because of constraints in space or time. Compared to medical applications the variance in size and materials is much larger. Adapting the acquisition trajectory to the object is beneficial and sometimes inevitable. There are currently no sophisticated methods for this adoption. Typically the operator places the object according to his best knowledge. We propose a detectability index based optimization algorithm which determines the scan trajectory on the basis of a CAD-model of the object. The detectability index is computed solely from simulated projections for multiple user defined features. By adapting the features the algorithm is adapted to different imaging tasks. Performance of simulated and measured data was qualitatively and quantitatively assessed.The results illustrate that our algorithm not only allows more accurate detection of features, but also delivers images with high overall quality in comparison to standard trajectory reconstructions. This work enables to reduce the number of projections and in consequence scan time by introducing an optimization algorithm to compose an object specific trajectory. PMID- 26817436 TI - Exploiting Information Diffusion Feature for Link Prediction in Sina Weibo. AB - The rapid development of online social networks (e.g., Twitter and Facebook) has promoted research related to social networks in which link prediction is a key problem. Although numerous attempts have been made for link prediction based on network structure, node attribute and so on, few of the current studies have considered the impact of information diffusion on link creation and prediction. This paper mainly addresses Sina Weibo, which is the largest microblog platform with Chinese characteristics, and proposes the hypothesis that information diffusion influences link creation and verifies the hypothesis based on real data analysis. We also detect an important feature from the information diffusion process, which is used to promote link prediction performance. Finally, the experimental results on Sina Weibo dataset have demonstrated the effectiveness of our methods. PMID- 26817438 TI - Is the tiger shark Galeocerdo cuvier a coastal species? Expanding its distribution range in the Atlantic Ocean using at-sea observer data. AB - The occurrence of tiger shark Galeocerdo cuvier in the Atlantic Ocean was assessed using at-sea observer data from multiple pelagic longline fisheries. Geographic positions of 2764 G. cuvier recorded between 1992 and 2013 and covering a wide area of the Atlantic Ocean were compared with the currently accepted distribution ranges of the species. Most records fell outside those ranges in both the Southern and Northern Hemispheres, which strongly suggests that the distribution range of G. cuvier in the open ocean is considerably larger than previously described. PMID- 26817439 TI - Successful Cryopreservation of Domestic Cat (Felis catus) Epididymal Sperm after Slow Equilibration to 15 or 10 degrees C. AB - To support conservation strategies in wild species, simple but highly reproducible procedures of sperm cryopreservation are required for an application under field conditions. We used epididymal sperm of the domestic cat to optimize a sperm freezing procedure for felid species, particularly questioning the demand for sperm cooling to 4 degrees C. We equilibrated sperm during slow cooling to only 15 or 10 degrees C in a Tes-Tris-fructose extender with final concentrations of 4.7% (v/v) glycerol and 10% (v/v) of the water-soluble fraction of hen's egg yolk (low-density lipoproteins). Subsequently, sperm were frozen over liquid nitrogen. Total and progressive motility (mean +/- SD) after thawing was 60.7 +/- 8.6% and 53.9 +/- 9.6% in samples cooled to 15 degrees C or 61.6 +/- 9.5% and 55.3 +/- 9.9% in samples cooled to 10 degrees C. Therefore, a one-step addition of glycerol to sperm at room temperature together with the freezing extender, the use of cryovials (loaded with diluted sperm aliquots of 300 MUl), an equilibration period of 40 min comprising slow cooling to 15 degrees C at a rate of approximately -0.14 K/min before rapid freezing over liquid nitrogen, yielded satisfying results. Cooling, freezing and thawing rates were exactly characterized as a prerequisite for further optimization and to provide a repeatable protocol to other practitioners. PMID- 26817440 TI - Electronic and Magnetic Properties of Encapsulated MoS2 Quantum Dots: The Case of Noble Metal Nanoparticle Dopants. AB - With the rise of 2D materials, such as graphene and transition metal dichalcogenides, as viable materials for numerous experimental applications, it becomes more necessary to maintain fine control of their properties. One expedient and efficacious technique to regulate their properties is surface functionalization. In this study, DFT calculations are performed on triangular MoS2 quantum dots (QDs) either partially or completely doped with nanoparticles (NPs) of the noble metals Au, Ag, and Pt. The effects of these dopants on the geometry, electronic properties, magnetic properties, and chemical bonding of the QDs are investigated. The calculations show that the structural stability of the QDs is reduced by Au or Ag dopants, whereas Pt dopants have a contrasting effect. The NPs diminish the metallicity of the QD, the extent of which is contingent on the number of NPs adsorbed on the QD. However, these NPs exert distinctly disparate charge transfer effects-Ag NPs n-dope the QDs, whereas Au and Pt NPs either n- or p-dope. The molecular electrostatic potential maps of the occupied states show that metallic states are removed from the doping sites. Notwithstanding the decrease of magnetization in all three types of hybrid QD, the distribution of spin density in the Pt-doped QD is inherently different from that in the other QDs. Bond analyses using the quantum theory of atoms in molecules and the crystal orbital Hamilton population suggest that bonds between the Pt NPs and the QDs are the most covalent and the strongest, followed by the Au-QD bonds, and then Ag-QD bonds. The versatility of these hybrid QDs is further examined by applying an external electric field in the three orthogonal orientations, and comparing their properties with those in the absence of the electric field. There are two primary observations: 1) dopants at the tail, head and tail, and in the fully encased configuration are most effective in modifying the distribution of metallic states if the electric field is absent, and 2) the metallic states in these aforementioned QDs are generally insensitive to the electric field. Conversely, the asymmetric electric effects on the charge transfer in these QDs have to be carefully monitored to allow finer control of their structural stability. This study aptly demonstrates the value of noble metal dopants for manipulating the properties of MoS2 QDs, and shows the versatility of these hybrid QDs as tunable nanodevices. This notably extends the functionality of these nanostructures for applications such as catalysis and nanoelectronics. PMID- 26817437 TI - GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways. AB - BACKGROUND: In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS) patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. METHODS: We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. RESULTS: Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. CONCLUSIONS: These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study. PMID- 26817441 TI - Testing a post-discharge nurse-led transitional home visit in acute care pediatrics: the Hospital-To-Home Outcomes (H2O) study protocol. AB - AIMS: The aims of this study were: (1) to explore the family perspective on pediatric hospital-to-home transitions; (2) to modify an existing nurse-delivered transitional home visit to better meet family needs; (3) to study the effectiveness of the modified visit for reducing healthcare re-use and improving patient- and family-centered outcomes in a randomized controlled trial. BACKGROUND: The transition from impatient hospitalization to outpatient care is a vulnerable time for children and their families; children are at risk for poor outcomes that may be mitigated by interventions to address transition difficulties. It is unknown if an effective adult transition intervention, a nurse home visit, improves postdischarge outcomes for children hospitalized with common conditions. DESIGN: (1) Descriptive qualitative; (2) Quality improvement; (3) Randomized controlled trial. METHODS: Aim 1 will use qualitative methods, through focus groups, to understand the family perspective of hospital-to-home transitions. Aim 2 will use quality improvement methods to modify the content and processes associated with nurse home visits. Modifications to visits will be made based on parent and stakeholder input obtained during Aims 1 & 2. The effectiveness of the modified visit will be evaluated in Aim 3 through a randomized controlled trial. DISCUSSION: We are undertaking the study to modify and evaluate a nurse home visit as an effective acute care pediatric transition intervention. We expect the results will be of interest to administrators, policy makers and clinicians interested in improving pediatric care transitions and associated postdischarge outcomes, in the light of impending bundled payment initiatives in pediatric care. PMID- 26817442 TI - Life Course Dietary Patterns and Bone Health in Later Life in a British Birth Cohort Study. AB - Evidence for the contribution of individual foods and nutrients to bone health is weak. Few studies have considered hypothesis-based dietary patterns and bone health. We investigated whether a protein-calcium-potassium-rich (PrCaK-rich) dietary pattern over the adult life course, was positively associated with bone outcomes at 60 to 64 years of age. Diet diaries were collected at ages 36, 46, 53, and 60 to 64 years in 1263 participants (661 women) from the MRC National Survey of Health and Development. DXA and pQCT measurements were obtained at age 60 to 64 years, including size-adjusted bone mineral content (SA-BMC) and volumetric bone mineral density (vBMD). A food-based dietary pattern best explaining dietary calcium, potassium, and protein intakes (g/1000 kcal) was identified using reduced rank regression. Dietary pattern Z-scores were calculated for each individual, at each time point. Individual trajectories in dietary pattern Z-scores were modeled to summarize changes in Z-scores over the study period. Regression models examined associations between these trajectories and bone outcomes at age 60 to 64 years, adjusting for baseline dietary pattern Z score and other confounders. A consistent PrCaK-rich dietary pattern was identified within the population, over time. Mean +/- SD dietary pattern Z-scores at age 36 years and age 60 to 64 years were -0.32 +/- 0.97 and 2.2 +/- 1.5 (women) and -0.35 +/- 0.98 and 1.7 +/- 1.6 (men), respectively. Mean trajectory in dietary pattern Z-scores +/- SD was 0.07 +/- 0.02 units/year. Among women, a 0.02-SD unit/year higher trajectory in dietary pattern Z-score over time was associated with higher SA-BMC (spine 1.40% [95% CI, 0.30 to 2.51]; hip 1.35% [95% CI, 0.48 to 2.23]), and vBMD (radius 1.81% [95% CI, 0.13 to 3.50]) at age 60 to 64 years. No statistically significant associations were found in men. During adulthood, an increasing score for a dietary pattern rich in protein, calcium, and potassium was associated with greater SA-BMC at fracture-prone sites in women. This study emphasizes the importance of these nutrients, within the context of the whole diet, to bone health. (c) 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR). PMID- 26817443 TI - Higher plasma levels of lysophosphatidylcholine 18:0 are related to a lower risk of common cancers in a prospective metabolomics study. AB - BACKGROUND: First metabolomics studies have indicated that metabolic fingerprints from accessible tissues might be useful to better understand the etiological links between metabolism and cancer. However, there is still a lack of prospective metabolomics studies on pre-diagnostic metabolic alterations and cancer risk. METHODS: Associations between pre-diagnostic levels of 120 circulating metabolites (acylcarnitines, amino acids, biogenic amines, phosphatidylcholines, sphingolipids, and hexoses) and the risks of breast, prostate, and colorectal cancer were evaluated by Cox regression analyses using data of a prospective case-cohort study including 835 incident cancer cases. RESULTS: The median follow-up duration was 8.3 years among non-cases and 6.5 years among incident cases of cancer. Higher levels of lysophosphatidylcholines (lysoPCs), and especially lysoPC a C18:0, were consistently related to lower risks of breast, prostate, and colorectal cancer, independent of background factors. In contrast, higher levels of phosphatidylcholine PC ae C30:0 were associated with increased cancer risk. There was no heterogeneity in the observed associations by lag time between blood draw and cancer diagnosis. CONCLUSION: Changes in blood lipid composition precede the diagnosis of common malignancies by several years. Considering the consistency of the present results across three cancer types the observed alterations point to a global metabolic shift in phosphatidylcholine metabolism that may drive tumorigenesis. PMID- 26817444 TI - Children's comprehension of an unfamiliar speaker accent: a review. AB - BACKGROUND: The effect of speaker accent on listeners' comprehension has become a key focus of research given the increasing cultural diversity of society and the increased likelihood of an individual encountering a clinician with an unfamiliar accent. AIMS: To review the studies exploring the effect of an unfamiliar accent on language comprehension in typically developing (TD) children and in children with speech and language difficulties. This review provides a methodological analysis of the relevant studies by exploring the challenges facing this field of research and highlighting the current gaps in the literature. METHODS & PROCEDURES: A total of nine studies were identified using a systematic search and organized under studies investigating the effect of speaker accent on language comprehension in (1) TD children and (2) children with speech and/or language difficulties. MAIN CONTRIBUTION: This review synthesizes the evidence that an unfamiliar speaker accent may lead to a breakdown in language comprehension in TD children and in children with speech difficulties. Moreover, it exposes the inconsistencies found in this field of research and highlights the lack of studies investigating the effect of speaker accent in children with language deficits. CONCLUSIONS & IMPLICATIONS: Overall, research points towards a developmental trend in children's ability to comprehend accent-related variations in speech. Vocabulary size, language exposure, exposure to different accents and adequate processing resources (e.g. attention) seem to play a key role in children's ability to understand unfamiliar accents. This review uncovered some inconsistencies in the literature that highlight the methodological issues that must be considered when conducting research in this field. It explores how such issues may be controlled in order to increase the validity and reliability of future research. Key clinical implications are also discussed. PMID- 26817447 TI - A 50-Year-Old Woman With Reticulate Hyperpigmentation. PMID- 26817445 TI - Prevalence of antibodies against Ehrlichia spp. and Orientia tsutsugamushi in small mammals around harbors in Taiwan. AB - BACKGROUND: Tick-borne ehrlichiosis and mite-borne scrub typhus represent important emerging zoonotic rickettsial diseases. Although scrub typhus has been recognized by the Taiwanese public health system, information on ehrlichial infections is scarce in Taiwan. In this study, the risk of spread of ectoparasites on rodents through aerial and marine transportation was assessed in international and domestic harbors. Here, we report the first systematic surveillance of seroprevalence against Ehrlichia spp. in small mammals on the main island of Taiwan. METHODS: In total, 1648 small mammals were trapped from 8 international ports, 18 domestic fishing harbors, and 7 local public health centers around Taiwan from November 2004 to December 2008. Sera were analyzed using indirect immunofluorescence assays to detect IgG antibodies against Ehrlichia chaffeensis and Orientia tsutsugamushi. A serum titer of ?1:80 was considered positive. RESULTS: Antibodies against Ehrlichia spp. and O. tsutsugamushi were detected in 3.28% and 4.92% of small mammals active around harbors, respectively. The seropositive rate against Ehrlichia was higher in northern Taiwan from 2005 to 2008. However, O. tsutsugamushi infections increased in southern Taiwan during this period. The serological evidence of ehrlichial and O. tsutsugamushi infections in all international ports were included in the study. No significant differences were found among the seropositive rates of Ehrlichia spp. and O. tsutsugamushi in small mammals trapped between international and local harbors. CONCLUSIONS: The overall prevalence of Ehrlichia spp. and O. tsutsugamushi infections in small mammals active around harbors was 3.28% and 4.92%, respectively. The results provided serological evidence supporting the potential risks of transporting pathogens through air and maritime traffic. This study highlights serious issues of the emergence and spread of rickettsial diseases in Taiwan. The incidence of human ehrlichiosis requires further investigation. PMID- 26817448 TI - Childhood Abuse and Military Experience-Important Information to Better Serve Those Who Have Served. PMID- 26817446 TI - Transcranial laser stimulation improves human cerebral oxygenation. AB - BACKGROUND AND OBJECTIVE: Transcranial laser stimulation of the brain with near infrared light is a novel form of non-invasive photobiomodulation or low-level laser therapy (LLLT) that has shown therapeutic potential in a variety of neurological and psychological conditions. Understanding of its neurophysiological effects is essential for mechanistic study and treatment evaluation. This study investigated how transcranial laser stimulation influences cerebral hemodynamics and oxygenation in the human brain in vivo using functional near-infrared spectroscopy (fNIRS). MATERIALS AND METHODS: Two separate experiments were conducted in which 1,064-nm laser stimulation was administered at (1) the center and (2) the right side of the forehead, respectively. The laser emitted at a power of 3.4 W and in an area of 13.6 cm2, corresponding to 0.25 W/cm2 irradiance. Stimulation duration was 10 minutes. Nine healthy male and female human participants of any ethnic background, in an age range of 18-40 years old were included in each experiment. RESULTS: In both experiments, transcranial laser stimulation induced an increase of oxygenated hemoglobin concentration (Delta[HbO2 ]) and a decrease of deoxygenated hemoglobin concentration (Delta[Hb]) in both cerebral hemispheres. Improvements in cerebral oxygenation were indicated by a significant increase of differential hemoglobin concentration (Delta[HbD] = Delta[HbO2 ] - Delta[Hb]). These effects increased in a dose-dependent manner over time during laser stimulation (10 minutes) and persisted after laser stimulation (6 minutes). The total hemoglobin concentration (Delta[HbT] = Delta[HbO2] + Delta[Hb]) remained nearly unchanged in most cases. CONCLUSION: Near-infrared laser stimulation applied to the forehead can transcranially improve cerebral oxygenation in healthy humans. PMID- 26817449 TI - Biomechanical walking mechanisms underlying the metabolic reduction caused by an autonomous exoskeleton. AB - BACKGROUND: Ankle exoskeletons can now reduce the metabolic cost of walking in humans without leg disability, but the biomechanical mechanisms that underlie this augmentation are not fully understood. In this study, we analyze the energetics and lower limb mechanics of human study participants walking with and without an active autonomous ankle exoskeleton previously shown to reduce the metabolic cost of walking. METHODS: We measured the metabolic, kinetic and kinematic effects of wearing a battery powered bilateral ankle exoskeleton. Six participants walked on a level treadmill at 1.4 m/s under three conditions: exoskeleton not worn, exoskeleton worn in a powered-on state, and exoskeleton worn in a powered-off state. Metabolic rates were measured with a portable pulmonary gas exchange unit, body marker positions with a motion capture system, and ground reaction forces with a force-plate instrumented treadmill. Inverse dynamics were then used to estimate ankle, knee and hip torques and mechanical powers. RESULTS: The active ankle exoskeleton provided a mean positive power of 0.105 +/- 0.008 W/kg per leg during the push-off region of stance phase. The net metabolic cost of walking with the active exoskeleton (3.28 +/- 0.10 W/kg) was an 11 +/- 4 % (p = 0.019) reduction compared to the cost of walking without the exoskeleton (3.71 +/- 0.14 W/kg). Wearing the ankle exoskeleton significantly reduced the mean positive power of the ankle joint by 0.033 +/- 0.006 W/kg (p = 0.007), the knee joint by 0.042 +/- 0.015 W/kg (p = 0.020), and the hip joint by 0.034 +/- 0.009 W/kg (p = 0.006). CONCLUSIONS: This study shows that the ankle exoskeleton does not exclusively reduce positive mechanical power at the ankle joint, but also mitigates positive power at the knee and hip. Furthermore, the active ankle exoskeleton did not simply replace biological ankle function in walking, but rather augmented the total (biological + exoskeletal) ankle moment and power. This study underscores the need for comprehensive models of human exoskeleton interaction and global optimization methods for the discovery of new control strategies that optimize the physiological impact of leg exoskeletons. PMID- 26817450 TI - Looking beyond GWAS: allele-specific transcription factor binding drives the association of GALNT2 to HDL-C plasma levels. AB - BACKGROUND: Plasma levels of high-density lipoprotein cholesterol (HDL-C) have been associated to cardiovascular disease. The high heritability of HDL-C plasma levels has been an incentive for several genome wide association studies (GWASs) which identified, among others, variants in the first intron of the GALNT2 gene strongly associated to HDL-C levels. However, the lead GWAS SNP associated to HDL C levels in this genomic region, rs4846914, is located outside of transcription factor (TF) binding sites defined by chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) experiments in the ENCODE project and is therefore unlikely to be functional. In this study we apply a bioinformatics approach which rely on the premise that ChIP-seq reads can identify allele specific binding of a TF at cell specific regulatory elements harboring allele specific SNPs (AS-SNPs). EMSA and luciferase assays were used to validate the allele specific binding and to test the enhancer activity of the regulatory element harboring the AS-SNP rs4846913 as well as the neighboring rs2144300 which are in high LD with rs4846914. FINDINGS: Using luciferase assays we found that rs4846913 and the neighboring rs2144300 displayed allele specific enhancer activity. We propose that an inhibitor binds preferentially to the rs4846913-C allele with an inhibitory boost from the synergistic binding of other TFs at the neighboring SNP rs2144300. These events influence the transcription level of GALNT2. CONCLUSIONS: The results suggest that rs4846913 and rs2144300 drive the association to HDL-C plasma levels through an inhibitory regulation of GALNT2 rather than the reported lead GWAS SNP rs4846914. PMID- 26817451 TI - Thrombocytosis and hyperfibrinogenemia are predictive factors of clinical outcomes in high-grade serous ovarian cancer patients. AB - BACKGROUND: Over 20% of ovarian cancer patients have preoperative thrombocytosis or hyperfibrinogenemia. We aimed to demonstrate the clinical and prognostic significance of thrombocytosis and hyperfibrinogenemia in high-grade serous ovarian cancer (HGSC). METHODS: We retrospectively investigated HGSC patients who underwent primary staging or debulking surgery between April 2005 and June 2013 in our institution. None of these patients had received neoadjuvant chemotherapy. Data, including age, performance status, FIGO stage, serum CA125, platelet count, fibrinogen level, and surgical residual disease, were collected. Thrombocytosis was defined as a platelet count greater than 450 * 10(9)/L, and hyperfibrinogenemia was defined as a fibrinogen level higher than 4.00 g/L. Progression-free survival (PFS) and overall survival (OS) were analyzed with the Kaplan-Meier method and log-rank tests for univariate analyses. For the multivariate analyses, Cox regression analysis was used to evaluate the effects of the prognostic factors, which are expressed as hazard ratios (HRs). RESULTS: A total of 875 consecutive HGSC patients were identified. The median follow-up time was 29 (1-115) months. The median (interquartile range, IQR) preoperative platelet count was 301 (235-383) * 10(9)/L, and 121 (13.8%) women had thrombocytosis. The median (IQR) preoperative fibrinogen level was 3.85 (3.19 4.45) g/L, and 332 (45.9%) of the patients had hyperfibrinogenemia. Both preoperative thrombocytosis and hyperfibrinogenemia were associated with an advanced FIGO stage (p = 0.008 and <0.001, respectively), an increased CA125 level (p = 0.004 and 0.001, respectively), more extensive ascites (p < 0.001 and <0.001, respectively), more extensive residual disease (p < 0.001 and <0.001, respectively) and chemosensitivity (p = 0.043 and <0.001, respectively). In the univariate analyses, hyperfibrinogenemia was associated with reduced PFS (p < 0.001) and OS (p < 0.001). However, thrombocytosis was not found to be a potential predictor of PFS (P = 0.098) or OS (p = 0.894). In the multivariate analyses, hyperfibrinogenemia was an independent predictor of OS (p = 0.014) but not PFS (p = 0.062). CONCLUSION: Preoperative thrombocytosis and hyperfibrinogenemia reflected tumor burden to some extent and thus influenced treatment outcomes, and the fibrinogen level was found to be useful as a prognostic predictor in the HGSC patients. PMID- 26817452 TI - Correlates of knee bone marrow lesions in younger adults. AB - BACKGROUND: Subchondral bone marrow lesions (BMLs) play a key role in the pathogenesis of osteoarthritis (OA) and are associated with pain and structural progression in knee OA. However, little is known about clinical significance and determinants of BMLs of the knee joint in younger adults. We aimed to describe the prevalence and environmental (physical activity), structural (cartilage defects, meniscal lesions) and clinical (pain, stiffness, physical dysfunction) correlates of BMLs in younger adults and to determine whether cholesterol levels measured 5 years prior were associated with current BMLs in young adults. METHODS: Subjects broadly representative of the Australian young adult population (n = 328, aged 31-41 years, female 48.7 %) underwent T1- and proton density weighted fat-suppressed magnetic resonance imaging (MRI) in their dominant knee. BMLs, cartilage defects, meniscal lesions and cartilage volume were measured. Knee pain was assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and physical activity was measured by the International Physical Activity Questionnaire (IPAQ). Cholesterol levels including high-density lipoprotein (HDL) were assessed 5 years prior to MRI. RESULTS: The overall prevalence of BML was 17 % (grade 1: 10.7 %, grade 2: 4.3 %, grade 3: 1.8 %). BML was positively associated with increasing age and previous knee injury but not body mass index. Moderate physical activity (prevalence ratio (PR):0.93, 95 % CI: 0.87, 0.99) and HDL cholesterol (PR:0.36, 95 % CI: 0.15, 0.87) were negatively associated with BML, while vigorous activity (PR:1.02, 95 % CI: 1.01, 1.03) was positively associated with medial tibiofemoral BMLs. BMLs were associated with more severe total WOMAC knee pain (>5 vs <=5, PR:1.05, 95 % CI: 1.02, 1.09) and WOMAC dysfunction (PR:1.75, 95 % CI: 1.07, 2.89), total knee cartilage defects (PR:2.65, 95 % CI: 1.47, 4.80) and total meniscal lesion score (PR:1.92, 95 % CI: 1.13, 3.28). CONCLUSIONS: BMLs in young adults are associated with knee symptoms and knee structural lesions. Moderate physical activity and HDL cholesterol are beneficially associated with BMLs; in contrast, vigorous physical activity is weakly but positively associated with medial tibiofemoral BMLs. PMID- 26817453 TI - Surgical management of appendiceal adenocarcinoid. Case report and literature review. AB - Adenocarcinoid tumour of the appendix is a rare entity characterised by the presence of a double component (neuroendocrine and glandular). It originates in the neuroendocrine cells of the appendicular mucosa. A preoperative diagnosis of a primary appendiceal tumour is uncommon and more so one suggesting an adenocarcinoid pathology. Optimal treatment is debated between a simple appendectomy and a more extensive resection, which occasionally includes hysterectomy and bilateral ovariectomy. Our aim is to report this rare entity and conduct a review of the literature on the different treatment options. PMID- 26817454 TI - Intralymphatic immunotherapy of pollen-induced rhinoconjunctivitis: a double blind placebo-controlled trial. AB - BACKGROUND: Allergen-specific immunotherapy represents the only disease-modifying treatment for allergic diseases. We and others have previously demonstrated that intralymphatic immunotherapy (ILIT), a less time-consuming alternative to conventional subcutaneous immunotherapy (SCIT), is safe and effective. However, this has recently been disputed. The aim of this study was therefore to expand our previous trial, further assessing the safety and efficacy of ILIT. METHODS: Thirty-six patients with pollen-induced rhinoconjunctivitis were randomised to receive three intralymphatic inguinal injections of active allergen (1000 SQ-U birch- or grass-pollen) or placebo. Clinical effects, safety and circulating immunological markers were assessed before, 4 weeks after treatment and at the end of the consecutive pollen season. RESULTS: No moderate or severe reactions were recorded following ILIT. Patients receiving active ILIT experienced a significant improvement in self-recorded seasonal allergic symptoms, as compared to placebo (p = 0.05). In a subgroup of these patients ("improved"), a reduction in nasal symptoms following nasal allergen provocation was also demonstrated. No changes in total IgE or IgG4 were found. However, the affinity of allergen specific IgG4 following active treatment was significantly increased, as compared to non-improved patients (p = 0.04). This could be correlated with clinical improvement, on an individual level. CONCLUSIONS: This double-blinded placebo controlled study confirms that ILIT is a safe and effective treatment for pollen induced rhinoconjunctivitis, markedly reducing seasonal allergic symptoms. TRIAL REGISTRATION: EudraCT: 2009-016815-39. PMID- 26817455 TI - Transcriptome profiling analysis for two Tibetan wild barley genotypes in responses to low nitrogen. AB - BACKGROUND: Nitrogen (N) is the most common limiting factor for crop productivity worldwide. An effective approach to solve N deficiency is to develop low N (LN) tolerant crop cultivars. Tibetan annual wild barley is well-known for its wide genetic diversity and high tolerance to poor soil fertility. Up to date, no study has been done to illustrate the mechanism of LN tolerance underlying the wild barley at transcriptional level. RESULTS: In this study, we employed Illumina RNA Sequencing to determine the genotypic difference in transcriptome profile using two Tibetan wild barley genotypes differing in LN tolerance (XZ149, tolerant and XZ56, sensitive). A total of 1469 differentially expressed genes (DEGs) were identified in the two genotypes at 6 h and 48 h after LN treatment. Genetic difference existed in DEGs between XZ149 and XZ56, including transporters, transcription factors (TFs), kinases, antioxidant stress and hormone signaling related genes. Meanwhile, 695 LN tolerance-associated DEGs were mainly mapped to amino acid metabolism, starch and sucrose metabolism and secondary metabolism, and involved in transporter activity, antioxidant activities, and other gene ontology (GO). XZ149 had a higher capability of N absorption and use efficiency under LN stress than XZ56. The higher expression of nitrate transporters and energy-saving assimilation pattern could be attributed to its more N uptake and higher LN tolerance. In addition, auxin (IAA) and ethylene (ETH) response pathways may be also related to the genotypic difference in LN tolerance. CONCLUSION: The responses of XZ149 and XZ56 to LN stress differed dramatically at transcriptional level. The identified candidate genes related to LN tolerance may provide new insights into comprehensive understanding of the genotypic difference in N utilization and LN tolerance. PMID- 26817456 TI - A Novel Application of Eddy Current Braking for Functional Strength Training During Gait. AB - Functional strength training is becoming increasingly popular when rehabilitating individuals with neurological injury such as stroke or cerebral palsy. Typically, resistance during walking is provided using cable robots or weights that are secured to the distal shank of the subject. However, there exists no device that is wearable and capable of providing resistance across the joint, allowing over ground gait training. In this study, we created a lightweight and wearable device using eddy current braking to provide resistance to the knee. We then validated the device by having subjects wear it during a walking task through varying resistance levels. Electromyography and kinematics were collected to assess the biomechanical effects of the device on the wearer. We found that eddy current braking provided resistance levels suitable for functional strength training of leg muscles in a package that is both lightweight and wearable. Applying resistive forces at the knee joint during gait resulted in significant increases in muscle activation of many of the muscles tested. A brief period of training also resulted in significant aftereffects once the resistance was removed. These results support the feasibility of the device for functional strength training during gait. Future research is warranted to test the clinical potential of the device in an injured population. PMID- 26817457 TI - Nondestructive Assessment of Engineered Cartilage Composition by Near Infrared Spectroscopy. AB - Tissue engineering presents a strategy to overcome the limitations of current tissue healing methods. Scaffolds, cells, external growth factors and mechanical input are combined in an effort to obtain constructs with properties that mimic native tissues. However, engineered constructs developed using similar culture environments can have very different matrix composition and biomechanical properties. Accordingly, a nondestructive technique to assess constructs during development such that appropriate compositional endpoints can be defined is desirable. Near infrared spectroscopy (NIRS) analysis is a modality being investigated to address the challenges associated with current evaluation techniques, which includes nondestructive compositional assessment. In the present study, cartilage tissue constructs were grown using chondrocytes seeded onto polyglycolic acid (PGA) scaffolds in similar environments in three separate tissue culture experiments and monitored using NIRS. Multivariate partial least squares (PLS) analysis models of NIR spectra were calculated and used to predict tissue composition, with biochemical assay information used as the reference data. Results showed that for combined data from all tissue culture experiments, PLS models were able to assess composition with significant correlations to reference values, including engineered cartilage water (at 5200 cm(-1), R = 0.68, p = 0.03), proteoglycan (at 4310 cm(-1), R = 0.82, p = 0.007), and collagen (at 4610 cm(-1), R = 0.84, p = 0.005). In addition, degradation of PGA was monitored using specific NIRS frequencies. These results demonstrate that NIR spectroscopy combined with multivariate analysis provides a nondestructive modality to assess engineered cartilage, which could provide information to determine the optimal time for tissue harvest for clinical applications. PMID- 26817459 TI - CP-CHARM: segmentation-free image classification made accessible. AB - BACKGROUND: Automated classification using machine learning often relies on features derived from segmenting individual objects, which can be difficult to automate. WND-CHARM is a previously developed classification algorithm in which features are computed on the whole image, thereby avoiding the need for segmentation. The algorithm obtained encouraging results but requires considerable computational expertise to execute. Furthermore, some benchmark sets have been shown to be subject to confounding artifacts that overestimate classification accuracy. RESULTS: We developed CP-CHARM, a user-friendly image based classification algorithm inspired by WND-CHARM in (i) its ability to capture a wide variety of morphological aspects of the image, and (ii) the absence of requirement for segmentation. In order to make such an image-based classification method easily accessible to the biological research community, CP CHARM relies on the widely-used open-source image analysis software CellProfiler for feature extraction. To validate our method, we reproduced WND-CHARM's results and ensured that CP-CHARM obtained comparable performance. We then successfully applied our approach on cell-based assay data and on tissue images. We designed these new training and test sets to reduce the effect of batch-related artifacts. CONCLUSIONS: The proposed method preserves the strengths of WND-CHARM - it extracts a wide variety of morphological features directly on whole images thereby avoiding the need for cell segmentation, but additionally, it makes the methods easily accessible for researchers without computational expertise by implementing them as a CellProfiler pipeline. It has been demonstrated to perform well on a wide range of bioimage classification problems, including on new datasets that have been carefully selected and annotated to minimize batch effects. This provides for the first time a realistic and reliable assessment of the whole image classification strategy. PMID- 26817458 TI - Nondestructive Techniques to Evaluate the Characteristics and Development of Engineered Cartilage. AB - In this review, methods for evaluating the properties of tissue engineered (TE) cartilage are described. Many of these have been developed for evaluating properties of native and osteoarthritic articular cartilage. However, with the increasing interest in engineering cartilage, specialized methods are needed for nondestructive evaluation of tissue while it is developing and after it is implanted. Such methods are needed, in part, due to the large inter- and intra donor variability in the performance of the cellular component of the tissue, which remains a barrier to delivering reliable TE cartilage for implantation. Using conventional destructive tests, such variability makes it near-impossible to predict the timing and outcome of the tissue engineering process at the level of a specific piece of engineered tissue and also makes it difficult to assess the impact of changing tissue engineering regimens. While it is clear that the true test of engineered cartilage is its performance after it is implanted, correlation of pre and post implantation properties determined non-destructively in vitro and/or in vivo with performance should lead to predictive methods to improve quality-control and to minimize the chances of implanting inferior tissue. PMID- 26817460 TI - Effect of transcutaneous acupoint electrical stimulation on propofol sedation: an electroencephalogram analysis of patients undergoing pituitary adenomas resection. AB - BACKGROUND: Transcutaneous acupoint electrical stimulation (TAES) as a needleless acupuncture has the same effect like traditional manual acupuncture. The combination of TAES and anesthesia has been proved valid in enhancing the anesthetic effects but its mechanisms are still not clear. METHODS: In this study, we investigated the effect of TAES on anesthesia with an electroencephalogram (EEG) oscillation analysis on surgery patients anesthetized with propofol, a widely-used anesthetic in clinical practice. EEG was continuously recorded during light and deep propofol sedation (target-controlled infusion set at 1.0 and 3.0 MUg/mL) in ten surgery patients with pituitary tumor excision. Each concentration of propofol was maintained for 6 min and TAES was given at 2-4 min. The changes in EEG power spectrum at different frequency bands (delta, theta, alpha, beta, and gamma) and the coherence of different EEG channels were analyzed. RESULTS: Our result showed that, after TAES application, the EEG power increased at alpha and beta bands in light sedation of propofol, but reduced at delta and beta bands in deep propofol sedation (p < 0.001). In addition, the EEG oscillation analysis showed an enhancement of synchronization at low frequencies and a decline in synchronization at high frequencies between different EEG channels in either light or deep propofol sedation. CONCLUSIONS: Our study showed evidence suggested that TAES may have different effects on propofol under light and deep sedation. TAES could enhance the sedative effect of propofol at low concentration but reduce the sedative effect of propofol at high concentration. PMID- 26817461 TI - Efficient dual sgRNA-directed large gene deletion in rabbit with CRISPR/Cas9 system. AB - The CRISPR RNA-guided Cas9 nuclease gene-targeting system has been extensively used to edit the genome of several organisms. However, most mutations reported to date have been are indels, resulting in multiple mutations and numerous alleles in targeted genes. In the present study, a large deletion of 105 kb in the TYR (tyrosinase) gene was generated in rabbit via a dual sgRNA-directed CRISPR/Cas9 system. The typical symptoms of albinism accompanied significantly decreased expression of TYR in the TYR knockout rabbits. Furthermore, the same genotype and albinism phenotype were found in the F1 generation, suggesting that large fragment deletions can be efficiently transmitted to the germline and stably inherited in offspring. Taken together, our data demonstrate that mono and biallelic large deletions can be achieved using the dual sgRNA-directed CRISPR/Cas9 system. This system produces no mosaic mutations or off-target effects, making it an efficient tool for large-fragment deletions in rabbit and other organisms. PMID- 26817463 TI - Practical Counseling Skills for the Pediatrician in the Indian Context. AB - Primary care pediatricians are often faced with children and families who need more than just a consultation. Pediatricians are also the first point of contact for many children and families in distress. Hence, the decision of whether to reassure and follow them up or refer them for an evaluation and management to a mental health professional is something all pediatricians find difficult to make. In order to serve their clients well, it is necessary that pediatricians are trained to identify and manage common child psychological/psychiatric problems. They may also be called upon to break bad news, motivate families to seek treatment and motivate children to accept offered treatment. Most training courses in Pediatrics do not offer skills training in counseling, making the transition to real life practice a difficult proposition. This paper focuses on what is counseling, what situations make it necessary for pediatricians to offer counseling, the methods that can be useful and some tips to improve communication, with an emphasis on unique issues in the Indian context. Some techniques that are simple, brief and can be used by pediatricians are discussed in this paper. PMID- 26817462 TI - Understanding how differentiation is maintained: lessons from the Drosophila brain. AB - The ability to maintain cells in a differentiated state and to prevent them from reprogramming into a multipotent state has recently emerged as a central theme in neural development as well as in oncogenesis. In the developing central nervous system (CNS) of the fruit fly Drosophila, several transcription factors were recently identified to be required in postmitotic cells to maintain differentiation, and in their absence, mature neurons undergo dedifferentiation, giving rise to proliferative neural stem cells and ultimately to tumor growth. In this review, we will highlight the current understanding of dedifferentiation and cell plasticity in the Drosophila CNS. PMID- 26817464 TI - Reversible MRI Changes in an Infant with Epileptic Spasms on Low Dose Vigabatrin. PMID- 26817465 TI - Mutation Spectrum and Phenotypic Features in Noonan Syndrome with PTPN11 Mutations: Definition of Two Novel Mutations. AB - OBJECTIVES: To evaluate the spectrum of PTPN11 gene mutations in Noonan syndrome patients and to study the genotype-phenotype associations. METHODS: In this study, twenty Noonan syndrome patients with PTPN11 mutations were included. The patients underwent a detailed clinical and physical evaluation. To identify inherited cases, parents of all mutation positive patients were analyzed. RESULTS: Thirteen different PTPN11 mutations, two of them being novel, were detected in the study group. These mutations included eleven missense mutations: p.G60A, p.D61N, p.Y62D, p.Y63C, p.E69Q, p.Q79R, p.Y279C,p.N308D, p.N308S, p.M504V, p.Q510R and two novel missense mutations: p.I56V and p.I282M. The frequency of cardiac abnormalities and short stature were found to be 80 % and 80 %, respectively. Mental retardation was not observed in patients having exon 8 mutations. No significant correlations were detected between other phenotypic features and genotypes. CONCLUSIONS: By identifying genotype-phenotype correlations, this study provides information on phenotypes observed in NS patients with different PTPN11 mutations. PMID- 26817466 TI - Typhoid Fever in Children below 2 years of Age. PMID- 26817467 TI - CNS Manifestations in Orientia tsutsugamushi Disease (Scrub Typhus) in North India. AB - OBJECTIVE: To present the clinical, lab profile and outcome of a series of six children who had features of meningoencephalitis (median age of 10.5 y) diagnosed as confirmed scrub typhus (ST) by using a lgM ELISA commercial kit (InBiOS International Inc. USA). METHODS: This was a prospective observational study conducted at a tertiary care hospital, over a period of 7 mo through April 2014. All the patients with undifferentiated febrile illness (aged 1-18 y) with fever of 5-21 d duration were evaluated. After thorough physical examination they were subjected to blood investigations such as complete blood count (CBC), blood culture, hepatic and kidney function tests, serum electrolytes, cerebrospinal fluid (CSF) analysis and IgM ELISA for scrub typhus, coagulogram and chest radiograph, wherever indicated. RESULTS: During this period, of the total 81 confirmed cases based on a positive scrub IgM ELISA and/or eschar, 6 (7.4 %), had neurological involvement in the form of presence of neck stiffness, altered sensorium and/or seizures and the CSF findings were suggestive of meningoencephalitis and all had evidence of multiple organ dysfunction syndrome (MODS) needing intensive care. The CECT could be performed in four patients only showing evidence of effacement of sulci and evidence of brain edema. CONCLUSIONS: This communication highlights that variable central nervous system (CNS) involvement is not uncommon in patients with scrub typhus with high mortality. CSF and neuro-radiology findings are nonspecific as these are also observed in patients with aseptic meningitis or encephalitis. Early suspection and institution of appropriate therapy without delay will lead to substantial reduction in the morbidity and mortality. PMID- 26817470 TI - Is antibiotic prophylaxis in nasal packing for anterior epistaxis needed? AB - Epistaxis is an extremely common problem that sometimes requires anterior nasal packing. Antibiotics are frequently indicated to prevent infectious complications, although the role of this measure is controversial. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified one systematic review including three primary studies, none of them randomized. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded it is not clear whether prophylactic antibiotics reduce infectious complications in patients with nasal packing for anterior epistaxis because the certainty of the evidence is very low. PMID- 26817469 TI - COX Inhibitor Influence on Skeletal Muscle Fiber Size and Metabolic Adaptations to Resistance Exercise in Older Adults. AB - Common cyclooxygenase (COX)-inhibiting drugs enhance resistance exercise induced muscle mass and strength gains in older individuals. The purpose of this investigation was to determine whether the underlying mechanism regulating this effect was specific to Type I or Type II muscle fibers, which have different contractile and metabolic profiles. Muscle biopsies (vastus lateralis) were obtained before and after 12 weeks of knee-extensor resistance exercise (3 days/week) from healthy older men who consumed either a placebo (n = 8; 64+/-2 years) or COX inhibitor (acetaminophen, 4 gram/day; n = 7; 64+/-1 years) in double-blind fashion. Muscle samples were examined for Type I and II fiber cross sectional area, capillarization, and metabolic enzyme activities (glycogen phosphorylase, citrate synthase, beta-hydroxyacyl-CoA-dehydrogenase). Type I fiber size did not change with training in the placebo group (304+/-590 MUm(2)) but increased 28% in the COX inhibitor group (1,388+/-760 MUm(2), p < .1). Type II fiber size increased 26% in the placebo group (1,432+/-499 MUm(2), p < .05) and 37% in the COX inhibitor group (1,825+/-400 MUm(2), p < .05). Muscle capillarization and enzyme activity were generally maintained in the placebo group. However, capillary to fiber ratio increased 24% (p < .1) and citrate synthase activity increased 18% (p < .05) in the COX inhibitor group. COX inhibitor consumption during resistance exercise in older individuals enhances myocellular growth, and this effect is more pronounced in Type I muscle fibers. PMID- 26817471 TI - Biodegradation of the cross-linked copolymer of acrylamide and potassium acrylate by soil bacteria. AB - Chemical cross-linking and the high molecular weight of superabsorbent copolymers (SAPs) are the two main causes of their resistance to biodegradation. However, SAP particles are colonized by microorganisms. For the purposes of this study, the dry technical copolymer of acrylamide and potassium acrylate containing 5.28 % of unpolymerized monomers was wrapped in a geotextile and incubated in unsterile Haplic Luvisol soil as a water absorbing geocomposite. The highest number of soil bacteria that colonized the hydrated SAP and utilized it as the sole carbon and energy source was found after the first month of incubation in soil. It was equal to 7.21-7.49 log10 cfu g(-1) of water absorbed by the SAP and decreased by 1.35-1.61 log10 units within the next 8 months. During this time, the initial SAP water holding capacity of 1665.8 g has decreased by 24.40 %. Moreover, the 5 g of SAP dry mass has declined by 31.70 %. Two bacteria, Rhizobium radiobacter 28SG and Bacillus aryabhattai 31SG isolated from the watered SAP were found to be able to biodegrade this SAP in pure cultures. They destroyed 25.07 and 41.85 mg of 300 mg of the technical SAP during the 60-day growth in mineral Burk's salt medium, and biodegradation activity was equal to 2.95 and 6.72 MUg of SAP MUg(-1) of protein, respectively. B. aryabhattai 31SG and R. radiobacter 28SG were also able to degrade 9.99 and 29.70 mg of 82 mg of the ultra-pure SAP in synthetic root exudate medium during the 30-day growth, respectively. PMID- 26817472 TI - Classification of diurnal patterns of particulate inorganic ions downwind of metropolitan Seoul. AB - The inorganic ions in PM2.5 were measured downwind of metropolitan Seoul using a particle-into-liquid sampler over three periods. Five diurnal patterns, including a low-concentration pattern (L) and a high-concentration pattern with a decreasing trend during the day (H-), were distinguished for the first period from February to June 2012. The sum of ion concentrations increased primarily due to NO3 (-) with decreasing temperature and increasing relative humidity, which caused preferential partitioning of NO3 (-) into the particulate phase. The peak concentration occurred during the morning rush hour for L but was delayed until the next morning for H- due to the time required to form secondary inorganic ions from accumulated pollutants under lower wind speeds. The characteristic features of the patterns observed during the first period were generally similar with those obtained for the other two periods. However, for the second period, comprised of colder months, changes in the diurnal patterns from L to H- were accompanied by increasing temperature, as the effect of photochemical formation of NO3 (-) was larger than that of volatilization. Although the role of long range transport was not distinct on the whole, the inflow of air masses from cleaner sectors was observed to lower the concentrations. PMID- 26817473 TI - Barium concentration in cast roe deer antlers related to air pollution caused by burning of barium-enriched coals in southern Poland. AB - Concentrations of Ba, Zn, Pb, Fe, and Mn were determined by atomic absorption spectroscopy in freshly cast antlers from male roe deer of different ages (2 to 4 years old and older than 4 years) collected in Balin near Chrzanow and in the vicinity of Zywiec, S Poland. Barium content ranged from 124 to 196 ppm (mean 165 ppm) in the Balin 12 samples and from 207 to 351 ppm (mean 287 ppm) in 3 antlers from Zywiec. The concentration of Ba was comparable to that of Zn (134-275 ppm, mean 169 ppm). Elevated concentrations of Ba in antlers most probably originated from direct uptake of airborne barite nanocrystals through the respiratory system and/or by digestion of barite-rich dust particles deposited on plants. Burning of Ba-enriched coals is regarded as the principal source of Ba in the investigated areas inhabited by roe deer. Increased concentrations of Ba in antlers from the Zywiec area compared to Balin reflect particularly high air pollution caused by coal-burning mostly for domestic purposes combined with an unfavorable topography that impedes efficient air circulation. PMID- 26817474 TI - Recyclable cross-linked laccase aggregates coupled to magnetic silica microbeads for elimination of pharmaceuticals from municipal wastewater. AB - In the present work, the use of magnetic mesoporous silica microbeads (MMSMB) as supports was proposed to produce magnetically-separable cross-linked enzyme aggregates (MCLEAs). The effects of cross linking time, addition of bovine serum albumin as protein feeder, pH, glutaraldehyde concentration, and laccase:MMSMB mass ratio on the immobilization yield and enzyme load were investigated. The best conditions allowed the rapid preparation of MCLEAs with high enzyme load, i.e., 1.53 U laccase/mg MCLEAs. The stability of MCLEAs was improved with regard to low pH, presence of chemical denaturants, and real wastewater matrix, compared to free laccase. In addition, the novel biocatalyst exhibited good operational stability, maintaining up to 70 % of its initial activity after 10 successive batch reactions. Finally, MCLEAs demonstrated its catalytic potential to transform acetaminophen and various non-phenolic pharmaceutical active compounds as mefenamic acid, fenofibrate, and indomethacin from biologically treated wastewater effluent, with similar or even higher efficiency than free laccase. PMID- 26817475 TI - What is this chocolate milk in my circuit? A cause of acute clotting of a continuous renal replacement circuit: Answers. PMID- 26817476 TI - Good-quality research in rare diseases: trials and tribulations. AB - Despite the fact that rare diseases affecting the kidney are not as uncommon as generally believed, proper clinical guidelines for guiding therapeutic management are scarce or absent owing to the overall lack of reliable scientific evidence. Although the randomized controlled trial (RCT) is the best study design for dealing with questions of intervention, RCTs under low-prevalence conditions are extremely challenging because of the limited number of patients, the variable phenotypic expression, and the long course of these disorders. In this brief review, we aimed to summarize the main alternative methods to traditional RCTs designed with the intent of minimizing the number of subjects needed for recruitment or maximizing the statistical efficiency of study analyses. Most of these approaches have not yet been extensively employed, may denote crucial limitations to wide applicability, or still lack proper validation in the field of rare diseases. Nevertheless, the growing number of proposed strategies is indicative of the perceived necessity by the scientific community to fill the quality gap between clinical guidelines for common and rare pathological conditions. PMID- 26817477 TI - Microbiome Regulation of Autoimmune, Gut and Liver Associated Diseases. AB - Extensive analysis of the complexity and diversity of microbiota using metagenomics in the gut and other body sites has provided evidence that dysbiosis occurs in many disease states. With the application of next generation sequencing technology this research is starting to uncover the impact of microbiota on metabolic, physiological and immunological pathways and elucidate the cellular and molecular mechanisms involved. To highlight these advances we have focused on autoimmunity and gut and liver related diseases and discuss the opportunities and challenges of translating microbiome research towards its application in humans. Towards this goal we discuss the application of fecal microbiome transplantation (FMT) for the treatment of multiple chronic gut associated inflammatory diseases such as Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). The potential role of human migration across continents and cultures leading to alteration in their microbiome and its implication in health and disease is also discussed. PMID- 26817479 TI - Congenital Vitiligo: A Case Report. PMID- 26817478 TI - Preparation, characterization, and in vitro release studies of insulin-loaded double-walled poly(lactide-co-glycolide) microspheres. AB - The purpose of this study was to fabricate insulin-loaded double-walled and single-polymer poly(lactide-co-glycolide) (PLGA) microspheres using a fast degrading glucose core, hydroxyl-terminated poly(lactide-co-glycolide) (Glu PLGA), and a moderate degrading carboxyl-terminated PLGA polymers. A modified water-in-oil-in-oil-in-water (w/o/o/w) emulsion solvent evaporation technique was employed to prepare double-walled microspheres, whereas single-polymer microspheres were fabricated by a conventional water-in-oil-in-water (w/o/w) emulsion solvent evaporation method. The effect of fabrication techniques and polymer characteristics on microspheres size, morphology, encapsulation efficiency, in vitro release, and insulin stability was evaluated. The prepared double-walled microspheres were essentially non-porous, smooth surfaced, and spherical in shape, whereas single-polymer microspheres were highly porous. Double-walled microspheres exhibited a significantly reduced initial burst followed by sustained and almost complete release of insulin compared to single polymer microspheres. Initial burst release was further suppressed from double walled microspheres when the mass ratio of the component polymers was increased. In conclusion, double-walled microspheres made of Glu-PLGA and PLGA can be a potential delivery system of therapeutic insulin. PMID- 26817480 TI - Proteogenomics: Opportunities and Caveats. PMID- 26817481 TI - Autologous simple limbal epithelial transplantation for unilateral limbal stem cell deficiency: multicentre results. AB - PURPOSE: To report outcomes of autologous simple limbal epithelial transplantation (SLET) performed for unilateral limbal stem cell deficiency (LSCD) at multiple centres worldwide. METHODS: In this retrospective, multicentre, interventional case series, records of patients who had undergone autologous SLET for unilateral LSCD, with a minimum of 6 months of follow-up, were reviewed. The primary outcome measure was clinical success, defined as a completely epithelised, avascular corneal surface. Kaplan-Meier survival curves were constructed and survival probability was calculated. A Cox proportional hazards analysis was done to assess association of preoperative characteristics with risk of failure. Secondary outcome measures included the percentage of eyes achieving visual acuity of 20/200 or better, percentage of eyes gaining two or more Snellen lines and complications encountered. RESULTS: 68 eyes of 68 patients underwent autologous SLET, performed across eight centres in three countries. Clinical success was achieved in 57 cases (83.8%). With a median follow-up of 12 months, survival probability exceeded 80%. Presence of symblepharon (HR 5.8) and simultaneous keratoplasty (HR 10.8) were found to be significantly associated with a risk of failure. 44 eyes (64.7%) achieved a visual acuity of 20/200 or better, and 44 eyes (64.7%) gained two or more Snellen lines. Focal recurrences of pannus were noted in 21 eyes (36.8%) with clinical success. CONCLUSION: Autologous SLET is an effective and safe modality for treatment of unilateral LSCD. Clinical success rates and visual acuity improvement are equal to or better than those reported with earlier techniques. PMID- 26817482 TI - Association between light-to-dark changes in angle width and iris parameters in light, dark and changes from light-to-dark conditions. AB - BACKGROUND/AIMS: To evaluate the association between light-to-dark changes in angle width parameters and iris parameters in light, dark and changes from light to-dark conditions. METHODS: In this prospective, cross-sectional study, anterior segment optical coherence tomography images, obtained under light and dark conditions, were analysed to determine angle opening distance measured at 500 MUm from the scleral spur (AOD500), trabecular-iris space area at 500 MUm from the scleral spur (TISA500), iris thickness measured at 750 MUm from the scleral spur (IT750), iris thickness measured at 2000 MUm from the scleral spur (IT2000), iris area (IArea) and pupil diameter (PD). Multivariable linear mixed-effect regression models were used to evaluate the association between light-to-dark changes in angle width parameters (AOD500, TISA500) and iris parameters (IT750, IT2000, IArea, PD) in light, dark and changes from light-to-dark conditions. RESULTS: 534 eyes from 314 non-glaucomatous subjects were analysed. IT750, IT2000, IArea and PD in light conditions were significantly associated with light to-dark changes in AOD500 (p<0.05). IT750, IT2000 and IArea in light conditions were significantly associated with light-to-dark changes in TISA500 (p<0.05). IT750 in dark conditions was significantly associated with light-to-dark changes in AOD500 and TISA500 (p<0.05). Light-to-dark changes in IT2000, IArea and PD were significantly associated with light-to-dark changes in AOD500 (p<0.05). Light-to-dark changes in IArea were significantly associated with light-to-dark changes in TISA500 (p<0.05). CONCLUSIONS: Evaluation of iris parameters in light, dark and changes from light-to-dark conditions demonstrated that IT750, IT2000, IArea and PD in light conditions are significant predictors of light-to-dark changes in angle width. PMID- 26817483 TI - Chronic inflammatory systemic diseases: An evolutionary trade-off between acutely beneficial but chronically harmful programs. AB - It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history stages, environmental factors of CIDs, energy trade-offs during inflammatory episodes and the non-specificity of CIDs. Incorporating bodily energy regulation into evolutionary medicine builds a framework to better understand pathophysiology of CIDs by considering that genes and networks used are positively selected if they serve acute, highly energy-consuming inflammation. It is predicted that genes that protect energy stores are positively selected (as immune memory). This could explain why energy-demanding inflammatory episodes like infectious diseases must be terminated within 3-8 weeks to be adaptive, and otherwise become maladaptive. Considering energy regulation as an evolved adaptive trait explains why many known sequelae of different CIDs must be uniform. These are, e.g. sickness behavior/fatigue/depressive symptoms, sleep disturbance, anorexia, malnutrition, muscle wasting-cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal (HPG) axis, hypertension, bone loss and hypercoagulability. Considering evolved energy trade-offs helps us to understand how an energy imbalance can lead to the disease sequelae of CIDs. In the future, clinicians must translate this knowledge into early diagnosis and symptomatic treatment in CIDs. PMID- 26817484 TI - Developmental contributions to macronutrient selection: a randomized controlled trial in adult survivors of malnutrition. AB - BACKGROUND AND OBJECTIVES: Birthweight differences between kwashiorkor and marasmus suggest that intrauterine factors influence the development of these syndromes of malnutrition and may modulate risk of obesity through dietary intake. We tested the hypotheses that the target protein intake in adulthood is associated with birthweight, and that protein leveraging to maintain this target protein intake would influence energy intake (EI) and body weight in adult survivors of malnutrition. METHODOLOGY: Sixty-three adult survivors of marasmus and kwashiorkor could freely compose a diet from foods containing 10, 15 and 25 percentage energy from protein (percentage of energy derived from protein (PEP); Phase 1) for 3 days. Participants were then randomized in Phase 2 (5 days) to diets with PEP fixed at 10%, 15% or 25%. RESULTS: Self-selected PEP was similar in both groups. In the groups combined, selected PEP was 14.7, which differed significantly (P < 0.0001) from the null expectation (16.7%) of no selection. Self-selected PEP was inversely related to birthweight, the effect disappearing after adjusting for sex and current body weight. In Phase 2, PEP correlated inversely with EI (P = 0.002) and weight change from Phase 1 to 2 (P = 0.002). Protein intake increased with increasing PEP, but to a lesser extent than energy increased with decreasing PEP. CONCLUSIONS AND IMPLICATIONS: Macronutrient intakes were not independently related to birthweight or diagnosis. In a free choice situation (Phase 1), subjects selected a dietary PEP significantly lower than random. Lower PEP diets induce increased energy and decreased protein intake, and are associated with weight gain. PMID- 26817485 TI - A deep sequencing tool for partitioning clearance rates following antimalarial treatment in polyclonal infections. AB - BACKGROUND AND OBJECTIVES: Current tools struggle to detect drug-resistant malaria parasites when infections contain multiple parasite clones, which is the norm in high transmission settings in Africa. Our aim was to develop and apply an approach for detecting resistance that overcomes the challenges of polyclonal infections without requiring a genetic marker for resistance. METHODOLOGY: Clinical samples from patients treated with artemisinin combination therapy were collected from Tanzania and Cambodia. By deeply sequencing a hypervariable locus, we quantified the relative abundance of parasite subpopulations (defined by haplotypes of that locus) within infections and revealed evolutionary dynamics during treatment. Slow clearance is a phenotypic, clinical marker of artemisinin resistance; we analyzed variation in clearance rates within infections by fitting parasite clearance curves to subpopulation data. RESULTS: In Tanzania, we found substantial variation in clearance rates within individual patients. Some parasite subpopulations cleared as slowly as resistant parasites observed in Cambodia. We evaluated possible explanations for these data, including resistance to drugs. Assuming slow clearance was a stable phenotype of subpopulations, simulations predicted that modest increases in their frequency could substantially increase time to cure. CONCLUSIONS AND IMPLICATIONS: By characterizing parasite subpopulations within patients, our method can detect rare, slow clearing parasites in vivo whose phenotypic effects would otherwise be masked. Since our approach can be applied to polyclonal infections even when the genetics underlying resistance are unknown, it could aid in monitoring the emergence of artemisinin resistance. Our application to Tanzanian samples uncovers rare subpopulations with worrying phenotypes for closer examination. PMID- 26817486 TI - Detection and characterization of two NDM-1-producing Klebsiella pneumoniae strains from Bulgaria. PMID- 26817487 TI - Accurate detection of Neisseria gonorrhoeae ciprofloxacin susceptibility directly from genital and extragenital clinical samples: towards genotype-guided antimicrobial therapy. AB - INTRODUCTION: Increasing use of nucleic acid amplification tests (NAATs) as the primary means of diagnosing gonococcal infection has resulted in diminished availability of Neisseria gonorrhoeae antimicrobial susceptibility data. We conducted a prospective diagnostic assessment of a real-time PCR assay (NGSNP) enabling direct detection of gonococcal ciprofloxacin susceptibility from a range of clinical sample types. METHODS: NGSNP, designed to discriminate an SNP associated with ciprofloxacin resistance within the N. gonorrhoeae genome, was validated using a characterized panel of geographically diverse isolates (n = 90) and evaluated to predict ciprofloxacin susceptibility directly on N. gonorrhoeae positive NAAT lysates derived from genital (n = 174) and non-genital (n = 116) samples (n = 290), from 222 culture-confirmed clinical episodes of gonococcal infection. RESULTS: NGSNP correctly genotyped all phenotypically susceptible (n = 49) and resistant (n = 41) panel isolates. Ciprofloxacin-resistant N. gonorrhoeae was responsible for infection in 29.7% (n = 66) of clinical episodes evaluated. Compared with phenotypic susceptibility testing, NGSNP demonstrated sensitivity and specificity of 95.8% (95% CI 91.5%-98.3%) and 100% (95% CI 94.7%-100%), respectively, for detecting ciprofloxacin-susceptible N. gonorrhoeae, with a positive predictive value of 100% (95% CI 97.7%-100%). Applied to urogenital (n = 164), rectal (n = 40) and pharyngeal samples alone (n = 30), positive predictive values were 100% (95% CI 96.8%-100%), 100% (95% CI 87.2%-100%) and 100% (95% CI 82.4%-100%), respectively. CONCLUSIONS: Genotypic prediction of N. gonorrhoeae ciprofloxacin susceptibility directly from clinical samples was highly accurate and, in the absence of culture, will facilitate use of tailored therapy for gonococcal infection, sparing use of current empirical treatment regimens and enhancing acquisition of susceptibility data for surveillance. PMID- 26817488 TI - Emergence of pan-resistance in KPC-2 carbapenemase-producing Klebsiella pneumoniae in Crete, Greece: a close call. AB - OBJECTIVES: KPC-2-producing Klebsiella pneumoniae (KPC-KP) ST258 has been rapidly expanding and is often associated with serious nosocomial infections. Last-line antibiotics such as colistin and tigecycline often remain the only treatment option. We describe here the evolving genetic background of KPC-KP isolates in Crete, Greece. METHODS: We tested the antibiotic susceptibility of 34 clinical isolates from patients hospitalized in 2010 and 2013-14. Whole-genome sequences of these isolates were analysed for acquired resistance genes and gene mutations. RESULTS: All KPC-KP isolates belonged to ST258 with the exception of one ST147 isolate. From 2014, 26% of isolates were non-susceptible to all antibiotics, compared with 0 of 11 isolates from 2010. Colistin resistance was associated with mutations in mgrB, which was present in 61% of isolates from 2014. Core-genome MLST analysis showed that pan-resistant isolates were closely related and appeared in two separate clusters. CONCLUSIONS: KPC-KP is rapidly evolving to pan resistance in Crete. We identified molecular resistance markers for pan-resistant isolates and showed that core-genome MLST is a promising tool for molecular fingerprinting of KPC-KP ST258. PMID- 26817489 TI - Smoking Among Pregnant Women in Outpatient Treatment for Opioid Dependence: A Qualitative Inquiry. AB - INTRODUCTION: Smoking during pregnancy is a major public health issue, contributing to adverse health outcomes. The vast majority of women with substance use disorders smoke during the perinatal period. Medication Assisted Treatment (MAT) is the standard of care for women using opioids during pregnancy. The majority of women engaged in MAT (88%-95%) report smoking. The purposes of this study were to describe: (1) facilitators and barriers to engaging in tobacco treatment among pregnant, opioid dependent women receiving MAT; and (2) strategies to tailor tobacco treatment interventions with this population. METHODS: Two semi-structured focus groups lasting approximately 45 minutes each were conducted with 22 women engaged in MAT. Focus groups were recorded, transcribed and analyzed in MAXQDA using content analysis. RESULTS: Participants reported: (1) desire to quit smoking for themselves and their children; (2) aversion to smoking; (3) a turning point in their lives from being pregnant and entering MAT; (4) nicotine dependence; (5) smoking as a way to cope with stress; (6) coping with dual dependencies; (7) past experiences with stopping smoking due to smoking restrictions; (8) perceived lack of success with nicotine replacement therapy or other tobacco treatment medications; and (9) the need for intensive environmental support for quit attempts. CONCLUSIONS: Participants were motivated to quit smoking, but faced multiple complex barriers. Integrating tobacco treatment into the psychosocial services offered in conjunction with MAT would allow a healthcare provider to offer tailored tobacco treatment in a supportive environment. IMPLICATIONS: Results of this qualitative study include facilitators and barriers to engaging in tobacco treatment among pregnant, opioid dependent women receiving MAT, as well as strategies to tailor tobacco treatment interventions for this population. In-depth knowledge of the complex barriers facing this patient population can be used to inform tailored tobacco treatment services that can be integrated into clinics providing MAT. PMID- 26817490 TI - Evaluation of Biomarkers of Exposure in Smokers Switching to a Carbon-Heated Tobacco Product: A Controlled, Randomized, Open-Label 5-Day Exposure Study. AB - INTRODUCTION: Tobacco harm reduction aims to provide reduced risk alternatives to adult smokers who would otherwise continue smoking combustible cigarettes (CCs). This randomized, open-label, three-arm, parallel-group, single-center, short-term confinement study aimed to investigate the effects of exposure to selected harmful and potentially harmful constituents (HPHCs) of cigarette smoke in adult smokers who switched to a carbon-heated tobacco product (CHTP) compared with adult smokers who continued to smoke CCs and those who abstained from smoking for 5 days. METHODS: Biomarkers of exposure to HPHCs, including nicotine and urinary excretion of mutagenic material, were measured in 24-hour urine and blood samples in 112 male and female Caucasian smokers switching from CCs to the CHTP ad libitum use. Puffing topography was assessed during product use. RESULTS: Switching to the CHTP or smoking abstinence (SA) resulted in marked decreases from baseline to Day 5 in all biomarkers of exposure measured, including carboxyhemoglobin (43% and 55% decrease in the CHTP and SA groups, respectively). The urinary excretion of mutagenic material was also markedly decreased on Day 5 compared with baseline (89% and 87% decrease in the CHTP and SA groups, respectively). No changes in biomarkers of exposure to HPHCs or urinary mutagenic material were observed between baseline and Day 5 in the CC group. CONCLUSIONS: Our results provide clear evidence supporting a reduction in the level of exposure to HPHCs of tobacco smoke in smokers who switch to CHTP under controlled conditions, similar to that observed in SA. IMPLICATIONS: The reductions observed in biomarkers of exposure to HPHCs of tobacco smoke in this short-term study could potentially also reduce the incidence of cancer, cardiovascular and respiratory diseases in those smokers who switch to a heated tobacco product. PMID- 26817492 TI - Cross-cultural study of caregiver burden for Alzheimer's disease in Japan and Taiwan: result from Dementia Research in Kumamoto and Tainan (DeReKaT). AB - BACKGROUND: Caregiver burden (CB) of Alzheimer's disease (AD) in Taiwan is becoming an urgent social issue as well as that in Japan. The comparison of CB may explain how caregiver feels burden in each country. METHODS: The participants were 343 outpatients with AD and their caregivers of Japan (n = 230) and Taiwan (n = 113). We assessed the CB using the Japanese and Chinese version of Zarit Caregiver Burden Interview (ZBI). The initial analysis was an exploratory factor analysis for each group to confirm the factor structure of ZBI. Then, the multiple-group structural equation modeling (MG-SEM) was used to assess the measurement invariance of ZBI such as configural, metric, and scalar invariances. Lastly, we compared the latent factor means of the ZBI between Japan and Taiwan. RESULTS: In both groups, the confirmatory factor analysis extracted 3 factors which were labeled "Impact on caregiver's life", "Embarrassed/anger", and "Dependency". The MG-SEM indicated an acceptable model fit, and established the partial scalar measurement invariance (comparative fit index (CFI) = 0.901, root mean square error of approximation (RMSEA) = 0.066). When we compared the latent factor means, the score of "Impact on caregiver's life" in Taiwanese caregivers was significantly higher than that in Japanese (p = 0.001). However, "Dependency" in Taiwanese caregivers was lower than that in Japanese (p < 0.001). CONCLUSIONS: Partial measurement invariance allowed comparing the latent factor mean across two countries. The results of comparisons suggested that there may be differences in the way of feeling CB between Japan and Taiwan. PMID- 26817491 TI - An Inventory of Methods for the Assessment of Additive Increased Addictiveness of Tobacco Products. AB - BACKGROUND: Cigarettes and other forms of tobacco contain the addictive drug nicotine. Other components, either naturally occurring in tobacco or additives that are intentionally added during the manufacturing process, may add to the addictiveness of tobacco products. As such, these components can make cigarette smokers more easily and heavily dependent.Efforts to regulate tobacco product dependence are emerging globally. Additives that increase tobacco dependence will be prohibited under the new European Tobacco Product Directive. OBJECTIVE: This article provides guidelines and recommendations for developing a regulatory strategy for assessment of increase in tobacco dependence due to additives. Relevant scientific literature is summarized and criteria and experimental studies that can define increased dependence of tobacco products are described. CONCLUSIONS: Natural tobacco smoke is a very complex matrix of components, therefore analysis of the contribution of an additive or a combination of additives to the level of dependence on this product is challenging. We propose to combine different type of studies analyzing overall tobacco product dependence potential and the functioning of additives in relation to nicotine. By using a combination of techniques, changes associated with nicotine dependence such as behavioral, physiological, and neurochemical alterations can be examined to provide sufficient information.Research needs and knowledge gaps will be discussed and recommendations will be made to translate current knowledge into legislation. As such, this article aids in implementation of the Tobacco Product Directive, as well as help enable regulators and researchers worldwide to develop standards to reduce dependence on tobacco products. IMPLICATIONS: This article provides an overall view on how to assess tobacco product constituents for their potential contribution to use and dependence. It provides guidelines that help enable regulators worldwide to develop standards to reduce dependence on tobacco products and guide researches to set research priorities on this topic. PMID- 26817493 TI - Dietary diversity, animal source food consumption and linear growth among children aged 1-5 years in Bandung, Indonesia: a longitudinal observational study. AB - Dietary diversity involves adequate intake of macronutrient and micronutrient. The inclusion of animal source foods (ASF) in the diet helps prevent multiple nutrient deficiencies and any resultant, linear growth retardation. The objective of the current study was to assess the relationship between dietary diversity, ASF consumption and height-for-age z-score (HAZ) among children aged 12-59 months old across a 1-year observation. This longitudinal observational study without controls was conducted among four age groups: 12-23 months (n 57), 24-35 months (n 56), 36-47 months (n 58) and 48-59 months (n 56). Anthropometry and dietary intake were measured during each of four visits at 16-20-week intervals. The general characteristics and other observations were only collected at baseline and endline. During the year-long study period, approximately 27 % of the children ate a diverse diet (consumed >=6 out of 9 food groups) according to >=3 visits. ASF consumption was high, particularly for eggs, poultry, processed meats and liquid milk. Yet, micronutrient intake inadequacy, especially of Zn, Ca, Fe and vitamin A, was highly prevalent. A multivariate regression analysis showed that the consumption of a diverse diet and ASF was not significantly associated with the HAZ at endline, after controlling for demographic characteristics and the baseline HAZ. The consumption of a diverse diet was significantly associated with Ca intake adequacy. Moreover, ASF consumption was significantly associated with adequate intake of protein and micronutrients, particularly vitamin A, Ca and Zn. Thus, the recommendation is to continue and strengthen the promotion of consuming a diverse diet that includes ASF in supporting the linear growth of young children. PMID- 26817494 TI - Exosomes for repair, regeneration and rejuvenation. AB - INTRODUCTION: Application of regenerative medicine strategies for repair of organs/tissue impacted by chronic disease is an active subject for product development. Such methodologies emphasize the role of stem cells as the active biological ingredient. However, recent developments in elucidating mechanisms of action of these therapies have focused on the role of paracrine, 'action-at-a distance' modus operandi in mediating the ability to catalyze regenerative outcomes without significant site-specific engraftment. A salient component of this secreted regenerative milieu are exosomes: 40-100 nm intraluminal vesicles that mediate transfer of proteins and nucleic acids across cellular boundaries. AREAS COVERED: Here, we synthesize recent studies from PubMed and Google Scholar highlighting how cell-based therapeutics and cosmeceutics are transitioning towards the secretome generally and exosomes specifically as a principal modulator of regenerative outcomes. EXPERT OPINION: Exosomes contribute to organ development and mediate regenerative outcomes in injury and disease that recapitulate observed bioactivity of stem cell populations. Encapsulation of the active biological ingredients of regeneration within non-living exosome carriers may offer process, manufacturing and regulatory advantages over stem cell-based therapies. PMID- 26817495 TI - Spatial masking: Development and testing of a new tinnitus assistive technology. AB - Masking is widely used in the management of tinnitus, however, masking at the perceived spatial location of tinnitus has not been investigated. This article examines the development of a method for the spatial masking of tinnitus. This report consists of three studies: Study I is a proof of concept study comparing customized spatial masking to conventional bilateral masking; Study II is a prototype evaluation in which the spatial masking paradigm was compared to a bilaterally equal masker using iPods connected to hearing aids in a 4-week cross over trial; and Study III is a 4-month crossover pilot study-using prototype hearing aid-based maskers, and in which three-dimensional (3D) masking (2 months) was compared to a Tinnitus Retraining Therapy (2 months). There was a preference for the 3D masking stimulus across all three studies. Individual changes in the Tinnitus Handicap Inventory (THI) after 2 weeks of trial (Study II) and Tinnitus Functional Index (TFI) after 2 months of trial (Study III) were observed without large group differences. The spatial masking concept was piloted successfully. The qualitative and quantitative results obtained indicate directions for future clinical trials and therapy development. This study indicates that spatial masking of tinnitus is feasible, of benefit to many participants, and warrants further trials. PMID- 26817496 TI - Changes in melatonin secretion in tourists after rapid movement to another lighting zone without transition of time zone. AB - Most of the research in the field of Chronobiology is focused on the problem of the circadian rhythms (CR) desynchronization. In travelers, it results mostly from the changes of surrounding: photoperiod, local climate conditions (radiation and thermal load) and behavior (e.g. type and place of tourism and activity level). Until now, it was not documented whether the changes in melatonin (MLT) secretion occur in effect of mid-distance transparallel travels (TpT), without complications arising due to time-zone transitions (e.g. jet-lag syndrome). To cope with this problem, a special field experiment was carried out. In the experiment, MLT characteristics were examined twice a year in real conditions through a group of young tourists (23-26 years old) at their place of habitual residence (Warsaw, Poland), and at their tourist destination (Tromso, Norway). Transition to circumpolar zone in summer has resulted in insignificant reduction in melatonin peak value (MPV) compared to preflight control (2 days before travel) and the melatonin peak time (MPT) was delayed. However, after traveling southward on the returning flight, MPV was lower compared to control and MPT was advanced. In winter, MPV was insignificantly higher in comparison to preflight control and MPT was almost unchanged. While changes in MPV do not depend on season, flight direction and day of stay after flight than MPT was differentiated seasonally and due to direction of flight. MPV and MPT were significantly modified by characteristics of individual light exposure during daytime and evening. The experiment showed also that in real conditions activity level is an important factor affected melatonin peak in tourists. In winter, greater daytime activity significantly influenced earlier MPT occurrence, both after northward and southward flights. PMID- 26817497 TI - Cost-effectiveness of non-vitamin K antagonist oral anticoagulants for stroke prevention in non-valvular atrial fibrillation: a systematic and qualitative review. AB - The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) into clinical practice represented a major change in the treatment of non-valvular atrial fibrillation (NVAF); drugs as effective as the gold standard were available, rapidly functioning and without major interferences with drugs and foods. However, a huge increase in the economic burden of NVAF was predicted, and many cost-effectiveness analyses were developed to aid policy makers and clinicians in implementing strategies for the prevention of stroke in NVAF. The present systematic review identified 54 studies from 21 different countries, reporting the incremental cost-effectiveness of dabigatran, apixaban, rivaroxaban and edoxaban. A critical appraisal of the studies was conducted in order to highlight consolidated results and biases. PMID- 26817498 TI - Secukinumab, a novel anti-IL-17A antibody, shows low immunogenicity potential in human in vitro assays comparable to other marketed biotherapeutics with low clinical immunogenicity. AB - Secukinumab is a human monoclonal antibody that selectively targets interleukin 17A and has been demonstrated to be highly efficacious in the treatment of moderate to severe plaque psoriasis, starting at early time points, with a sustained effect and a favorable safety profile. Biotherapeutics--including monoclonal antibodies (mAbs)--can be immunogenic, leading to formation of anti drug antibodies (ADAs) that can result in unwanted effects, including hypersensitivity reactions or compromised therapeutic efficacy. To gain insight into possible explanations for the clinically observed low immunogenicity of secukinumab, we evaluated its immunogenicity potential by applying 2 different in vitro assays: T-cell activation and major histocompatibility complex-associated peptide proteomics (MAPPs). For both assays, monocyte-derived dendritic cells (DCs) from healthy donors were exposed in vitro to biotherapeutic proteins. DCs naturally process proteins and present the derived peptides in the context of human leukocyte antigen (HLA)-class II. HLA-DR-associated biotherapeutic-derived peptides, representing potential T-cell epitopes, were identified in the MAPPs assay. In the T-cell assay, autologous CD4(+) T cells were co-cultured with secukinumab-exposed DCs and T-cell activation was measured by proliferation and interleukin-2 secretion. In the MAPPs analysis and T-cell activation assays, secukinumab consistently showed relatively low numbers of potential T-cell epitopes and low T-cell response rates, respectively, comparable to other biotherapeutics with known low clinical immunogenicity. In contrast, biotherapeutics with elevated clinical immunogenicity rates showed increased numbers of potential T-cell epitopes and increased T-cell response rates in T cell activation assays, indicating an approximate correlation between in vitro assay results and clinical immunogenicity incidence. PMID- 26817499 TI - In Situ "Clickable" Zwitterionic Starch-Based Hydrogel for 3D Cell Encapsulation. AB - Three-dimensional (3D) cell encapsulation in hydrogel provides superb methods to investigate the biochemical cues in directing cellular fate and behaviors outside the organism, the primary step of which is to establish suitable "blank platform" to mimic and simplify native ECM microenvironment. In this study, zwitterionic starch-based "clickable" hydrogels were fabricated via a "copper- and light- free" Michael-type "thiol-ene" addition reaction between acylated-modified sulfobetaine-derived starch (SB-ST-A) and dithiol-functionalized poly(ethylene glycol) (PEG-SH). By incorporating antifouling SB-ST and PEG, the hydrogel system would be excellently protected from nontarget protein adsorption to act as a "blank platform". The hydrogels could rapidly gel under physiological conditions in less than 7 min. Dynamic rheology experiments suggested the stiffness of the hydrogel was close to the native tissues, and the mechanical properties as well as the gelation times and swelling behaviors could be easily tuned by varying the precursor proportions. The protein and cell adhesion assays demonstrated that the hydrogel surface could effectively resist nonspecific protein and cell adhesion. The degradation study in vitro confirmed that the hydrogel was biodegradable. A549 cells encapsulated in the hydrogel maintained high viability (up to 93%) and started to proliferate in number and extend in morphology after 2 days' culture. These results indicated the hydrogel presented here could be a potential candidate as "blank platform" for 3D cell encapsulation and biochemical cues induced cellular behavior investigation in vitro. PMID- 26817500 TI - Progress and Perspectives of Plasmon-Enhanced Solar Energy Conversion. AB - Plasmonics allows extraordinary control of light, making it attractive for application in solar energy harvesting. In metal-semiconductor heterojunctions, plasmons can enhance photoconversion in the semiconductor via three mechanisms, including light trapping, hot electron/hole transfer, and plasmon-induced resonance energy transfer (PIRET). To understand the plasmonic enhancement, the metal's geometry, constituent metal, and interface must be viewed in terms of the effects on the plasmon's dephasing and decay route. To simplify design of plasmonic metal-semiconductor heterojunctions for high-efficiency solar energy conversion, the parameters controlling the plasmonic enhancement can be distilled to the dephasing time. The plasmonic geometry can then be further refined to optimize hot carrier transfer, PIRET, or light trapping. PMID- 26817501 TI - Analysis on correlation between SP and NK-1R and intranasal mucosal contact point headache. AB - CONCLUSION: Distribution of SP and NK-1R, especially NK-1R, in nasal mucosal tissue at contact point was higher compared with non-contact point. It was suggested that SP and NK-1R were associated with mucosal contact point headache. OBJECTIVES: To observe difference of substance P (SP) and NK-1 receptor (NK-1R) expression in tissues at contact point and non-contact point among the patients with intranasal mucosal contact point headache and speculate the role of SP and NK-1R in mucosal contact point headache. METHODS: SP and NK-1R in tissues of contact point and non-contact point among 40 patients with intranasal mucosal contact point headache were stained histologically by immunohistochemistry, and the mRNA level was detected by RT-PCR. RESULTS: SP was located in cytoplasm of acini epithelial cells, distributed in nasal mucosa tissues at both contact point and non-contact point. However, stain intensity was significantly increased at contact point (Z = -2.554, p < 0.05). NK-1R was located in the cytoplasm of acinar epithelial cells, inflammatory cells, and nerve fibers of contact point; only in cytoplasm of acinar epithelial cells and nerve fibers of non-contact point. Tinctorial rate of NK-1R increased significantly at contact point (chi(2) = 40.438, p < 0.01). mRNA level of SP and NK-1R was up-regulated in nasal mucosa at contact point compared with non-contact point. PMID- 26817502 TI - Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly: a randomized, double-blind, placebo controlled trial. AB - BACKGROUND: Zinc is essential for the regulation of immune response. T cell function declines with age. Zinc supplementation has the potential to improve the serum zinc concentrations and immunity of nursing home elderly with a low serum zinc concentration. OBJECTIVE: We aimed to determine the effect of supplementation with 30 mg Zn/d for 3 mo on serum zinc concentrations of zinc deficient nursing home elderly. DESIGN: This was a randomized, double-blind, placebo-controlled study. Of 53 nursing home elderly (aged >=65 y) who met eligibility criteria, 58% had a low serum zinc concentration (serum zinc <70 MUg/dL); these 31 were randomly assigned to zinc (30 mg Zn/d) (n = 16) or placebo (5 mg Zn/d) (n = 15) groups. The primary outcome measure was change in serum zinc concentrations between baseline and month 3. We also explored the effects of supplementation on immune response. RESULTS: Baseline characteristics were similar in the 2 groups. The difference in the mean change in serum zinc was significantly higher, by 16%, in the zinc group than in the placebo group (P = 0.007) when baseline zinc concentrations were controlled for. In addition, controlling for baseline C-reactive protein, copper, or albumin did not change the results. However, supplementation of participants with <=60 MUg serum Zn/dL failed to increase their serum zinc to >=70 MUg/dL. Zinc supplementation also significantly increased anti-CD3/CD28 and phytohemagglutinin-stimulated T cell proliferation, and the number of peripheral T cells (P < 0.05). When proliferation was expressed per number of T cells, the significant differences between groups were lost, suggesting that the zinc-induced enhancement of T cell proliferation was mainly due to an increase in the number of T cells. CONCLUSIONS: Zinc supplementation at 30 mg/d for 3 mo is effective in increasing serum zinc concentrations in nursing home elderly; however, not all zinc deficient elderly reached adequate concentrations. The increase in serum zinc concentration was associated with the enhancement of T cell function mainly because of an increase in the number of T cells. PMID- 26817503 TI - Effect of zinc and multivitamin supplementation on the growth of Tanzanian children aged 6-84 wk: a randomized, placebo-controlled, double-blind trial. AB - BACKGROUND: Poor child growth increases risks of mortality and morbidity. Micronutrient supplements have the potential to improve child growth. OBJECTIVE: We assessed the effect of daily zinc, multivitamin (vitamins C, E, and B complex), and zinc and multivitamin (Zn+MV) supplementation on growth in infants in Tanzania. DESIGN: In this randomized, 2 * 2 factorial, double-blind trial, 2400 infants were randomly assigned to receive zinc, multivitamins, Zn+MVs, or a placebo at 6 wk of age and were followed up for 18 mo with monthly growth measurements. Mixed-effects models with restricted cubic splines for the mean change in anthropometric z scores were fit for each group. Likelihood ratio tests were used to compare the effect of supplements on growth trajectories. Cox proportional hazards models were used to compare incidences of stunting, wasting, and underweight. RESULTS: Children in all groups experienced growth faltering. At 19 mo of age, prevalences of stunting, wasting, and underweight were 19.8%, 6.0%, and 10.8%, respectively. Changes in weight-for-age z scores (WAZs) and weight-for height z scores (WHZs) were significantly different across the 4 groups (P < 0.001 for both). The mean +/- SE decline in the WAZ from baseline to the end of follow-up in the Zn+MV group was significantly less than in the placebo group ( 0.36 +/- 0.04 compared with -0.50 +/- 0.04; P = 0.020), whereas the decline in the WHZ was significantly greater in the zinc-only group than in the placebo group (-0.57 +/- 0.07 compared with -0.35 +/- 0.07; P = 0.021). Supplements did not have a significant effect on mean change in the height-for-age z score or on rates of stunting, wasting, or underweight. CONCLUSIONS: Although there were small but significant improvements in the WAZ in the Zn+MV group, daily zinc supplementation alone, multivitamin supplementation alone, and the combined Zn+MV did not reduce the incidences of underweight, stunting, or wasting in Tanzanian infants. Alternative approaches to prevent growth faltering should be pursued. This trial was registered at clinicaltrials.gov as NCT00421668. PMID- 26817505 TI - The motilin receptor agonist erythromycin stimulates hunger and food intake through a cholinergic pathway. AB - BACKGROUND: Motilin-induced phase III contractions have been identified as a hunger signal. These phase III contractions occur as part of the migrating motor complex (MMC), a contractility pattern of the gastrointestinal tract during fasting. The mechanism involved in this association between subjective hunger feelings and gastrointestinal motility during the MMC is largely unknown, however, as is its ability to stimulate food intake. OBJECTIVES: We sought to 1) investigate the occurrence of hunger peaks and their relation to phase III contractions, 2) evaluate whether this relation was cholinergically driven, and 3) assess the ability of the motilin receptor agonist erythromycin to induce food intake. DESIGN: An algorithm was developed to detect hunger peaks. The association with phase III contractions was studied in 14 healthy volunteers [50% men; mean +/- SEM age: 25 +/- 2 y; mean +/- SEM body mass index (BMI; in kg/m(2)): 23 +/- 1]. The impact of pharmacologically induced phase III contractions on the occurrence of hunger peaks and the involvement of a cholinergic pathway were assessed in 14 healthy volunteers (43% men; age: 29 +/- 3 y; BMI: 23 +/- 1). Last, the effect of erythromycin administration on food intake was examined in 15 healthy volunteers (40% men; age: 28 +/- 3 y; BMI: 22 +/- 1). RESULTS: The occurrence of hunger peaks and their significant association with phase III contractions was confirmed (P < 0.0001). Pharmacologically induced phase III contractions were also significantly associated with hunger peaks (P < 0.05), and this association involved a cholinergic pathway. Administering erythromycin significantly stimulated food intake compared with placebo (53% +/- 13% compared with 10% +/- 5%; P < 0.05). CONCLUSIONS: Motilin-induced phase III contractions induced hunger feelings through a cholinergic pathway. Moreover, erythromycin stimulated food intake, suggesting a physiologic role of motilin as an orexigenic signal from the gastrointestinal tract. This trial was registered at www.clinicaltrials.gov as NCT02633579. PMID- 26817504 TI - Dietary lycopene intake and risk of prostate cancer defined by ERG protein expression. AB - BACKGROUND: There is limited evidence that supports etiologically distinct molecular subtypes of prostate cancer, the identification of which may improve prevention. Given their antioxidant properties, we hypothesized that lycopene and tomato sauce may be especially protective against diseases harboring the common gene fusion transmembrane protease, serine 2 (TMPRSS2):v-ets avian erythroblastosis virus E26 oncogene homolog (ERG). OBJECTIVE: We aimed to examine associations between estimated lycopene and tomato sauce intake and the risk of prostate cancer defined by ERG protein expression subtype. DESIGN: Our study population consisted of a prospective cohort of 46,719 men from the Health Professionals Follow-Up Study. TMPRSS2:ERG was assessed by ERG immunohistochemistry on tumor tissue microarrays constructed from radical prostatectomy specimens. We used multivariable competing risk models to calculate HRs and 95% CIs for the risk of ERG-positive and, separately, ERG-negative disease. We implemented inverse probability weighting to account for evaluating ERG status only in surgically treated cases. RESULTS: During 23 y of follow-up, 5543 men were diagnosed with prostate cancer, among whom 884 were assayed for ERG (426 ERG-positive). With inclusion of only the latter cases, increasing cumulative average tomato sauce intake was associated with a decreased risk of prostate cancer overall (>=2 servings/wk compared with <1 serving/mo; multivariable HR: 0.70; 95% CI: 0.52, 0.95; P-trend = 0.002). With respect to molecular subtypes, cumulative average tomato sauce intake was associated with a decreased risk of ERG-positive disease (HR: 0.54; 95% CI: 0.37, 0.81; P-trend = 0.004) but not with ERG-negative disease (HR: 0.96; 95% CI: 0.62, 1.50; P-trend = 0.10) (P-heterogeneity = 0.04). Increasing quintiles of lycopene intake were associated with a decreased risk of both subtypes (P-heterogeneity = 0.79). Inverse probability weighting did not materially change the results. CONCLUSIONS: Our results lend some support to the hypothesis that prostate cancers that harbor TMPRSS2:ERG may be etiologically distinct from fusion-negative cancers. In particular, tomato sauce consumption may play a role in reducing TMPRSS2:ERG positive disease. PMID- 26817506 TI - Higher compared with lower dietary protein during an energy deficit combined with intense exercise promotes greater lean mass gain and fat mass loss: a randomized trial. AB - BACKGROUND: A dietary protein intake higher than the Recommended Dietary Allowance during an energy deficit helps to preserve lean body mass (LBM), particularly when combined with exercise. OBJECTIVE: The purpose of this study was to conduct a proof-of-principle trial to test whether manipulation of dietary protein intake during a marked energy deficit in addition to intense exercise training would affect changes in body composition. DESIGN: We used a single blind, randomized, parallel-group prospective trial. During a 4-wk period, we provided hypoenergetic (~40% reduction compared with requirements) diets providing 33 +/- 1 kcal/kg LBM to young men who were randomly assigned (n = 20/group) to consume either a lower-protein (1.2 g . kg(-1) . d(-1)) control diet (CON) or a higher-protein (2.4 g . kg(-1) . d(-1)) diet (PRO). All subjects performed resistance exercise training combined with high-intensity interval training for 6 d/wk. A 4-compartment model assessment of body composition was made pre- and postintervention. RESULTS: As a result of the intervention, LBM increased (P < 0.05) in the PRO group (1.2 +/- 1.0 kg) and to a greater extent (P < 0.05) compared with the CON group (0.1 +/- 1.0 kg). The PRO group had a greater loss of fat mass than did the CON group (PRO: -4.8 +/- 1.6 kg; CON: -3.5 +/- 1.4kg; P < 0.05). All measures of exercise performance improved similarly in the PRO and CON groups as a result of the intervention with no effect of protein supplementation. Changes in serum cortisol during the intervention were associated with changes in body fat (r = 0.39, P = 0.01) and LBM (r = -0.34, P = 0.03). CONCLUSIONS: Our results showed that, during a marked energy deficit, consumption of a diet containing 2.4 g protein . kg(-1) . d(-1) was more effective than consumption of a diet containing 1.2 g protein . kg(-1) . d(-1) in promoting increases in LBM and losses of fat mass when combined with a high volume of resistance and anaerobic exercise. Changes in serum cortisol were associated with changes in body fat and LBM, but did not explain much variance in either measure. This trial was registered at clinicaltrials.gov as NCT01776359. PMID- 26817508 TI - Is there any relationship between drug addiction and the development of a signet ring cell carcinoma of the stomach? AB - We present three young patients diagnosed with signet ring cell carcinoma of the stomach. All had in common the smoking rather than the injecting route of administration of drugs, such as heroin. In the smoking route, pieces of nickel scourer are mixed with the drug. This heavy metal has known carcinogenic effects. Chronic exposure of the gastric mucosa to nickel, from oropharynx, could be a risk factor for the development of gastric adenocarcinoma in heroin smoking addicts. PMID- 26817507 TI - Growth and obesity through the first 7 y of life in association with levels of maternal glycemia during pregnancy: a prospective cohort study. AB - BACKGROUND: Given the long-term adverse sequelae of childhood obesity, identification of early life factors related to fetal growth and childhood obesity is warranted. Investigation on growth and obesity in early life in association with intrauterine exposure to maternal hyperglycemia, a common metabolic pregnancy complication, is of public health significance and clinical implications. OBJECTIVE: We investigated the association of fasting plasma glucose (FPG) concentrations during pregnancy with offspring growth and risk of overweight/obesity through age 7 y, after adjustment for confounders, including maternal prepregnancy obesity status. DESIGN: FPG concentrations at 28 gestational weeks (IQR: 22-32 wk) were extracted from medical records for 661 pregnancies complicated by gestational diabetes mellitus in the Danish National Birth Cohort (1996-2002). Offspring's ponderal index was derived from birth weight and length; age- and sex-specific body mass index (BMI) z scores at 5 mo, 12 mo, and 7 y were calculated based on WHO reference data. Relations between FPG and offspring growth and obesity were assessed by linear and Poisson regression with robust standard errors, adjusting for maternal prepregnancy BMI and sociodemographic and perinatal factors. RESULTS: At birth, maternal FPG during pregnancy was significantly associated with offspring ponderal index (beta = 0.46; 95% CI: 0.14, 0.78 per 1-mmol/L increase) and risk of macrosomia (birth weight >4000 g) (RR = 1.21; 95% CI: 1.07, 1.38 per 1-mmol/L increase). At 7 y, higher maternal FPG concentrations were significantly associated with increased BMI z scores (beta = 0.20; 95% CI: 0.04, 0.36) and elevated risk of overweight/obesity (RR = 1.21; 95% CI: 1.01, 1.50). Additional adjustment for birth weight and childhood lifestyle factors did not appreciably alter results. No associations were observed at 5 or 12 mo. CONCLUSION: Among women with gestational diabetes mellitus, maternal FPG concentrations during pregnancy were significantly and positively associated with offspring birth size and overweight/obesity risk at 7 y, adjusting for maternal prepregnancy BMI. PMID- 26817509 TI - Is ursodeoxycholic acid effective for intrahepatic cholestasis of pregnancy? AB - Intrahepatic cholestasis of pregnancy is a condition associated with fetal morbidity and mortality. Ursodeoxycholic acid has been proposed as a treatment alternative, but its use remains controversial. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including eight randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded ursodeoxycholic acid reduces prematurity risk and need for admission in neonatal intensive care units. It might also reduce maternal pruritus. PMID- 26817510 TI - Comparison of short-term energy intake and appetite responses to active and seated video gaming, in 8-11-year-old boys. AB - The acute effects of active and seated video gaming on energy intake (EI), blood glucose, plasma glucagon-like peptide-1 (GLP-17-36) and subjective appetite (hunger, prospective food consumption and fullness) were examined in 8-11-year old boys. In a randomised, crossover manner, twenty-two boys completed one 90-min active and one 90-min seated video gaming trial during which food and drinks were provided ad libitum. EI, plasma GLP-17-36, blood glucose and subjective appetite were measured during and following both trials. Time-averaged AUC blood glucose was increased (P=0.037); however, EI was lower during active video gaming (1.63 (sem 0.26) MJ) compared with seated video gaming (2.65 (sem 0.32) MJ) (P=0.000). In a post-gaming test meal 1 h later, there were no significant differences in EI between the active and seated gaming trials. Although estimated energy expenditure was significantly higher during active video gaming, there was still no compensation for the lower EI. At cessation of the trials, relative EI (REI) was significantly lower following active video gaming (2.06 (sem 0.30) MJ) v. seated video gaming (3.34 (sem 0.35) MJ) (P=0.000). No significant differences were detected in time-averaged AUC GLP-17-36 or subjective appetite. At cessation of the active video gaming trial, EI and REI were significantly less than for seated video gaming. In spite of this, the REI established for active video gaming was a considerable amount when considering the total daily estimated average requirement for 8-11-year-old boys in the UK (7.70 MJ). PMID- 26817511 TI - Examination of level of knowledge in Italian general practitioners attending an education session on diagnosis and management of the early stage of Alzheimer's disease: pass or fail? AB - BACKGROUND: We detected the general level of knowledge about the early diagnosis of Alzheimer's disease (AD) and subsequent care in general practitioners (GPs) from Southern Italy. We explored also the GP perception about their knowledge and training on diagnosis and management of AD. METHODS: On a sample of 131 GPs, we administered two questionnaires: the GP-Knowledge, evaluating GPs' expertise about AD epidemiology, differential diagnosis, and available treatments, and the GP-QUestionnaire on Awareness of Dementia (GP-QUAD), assessing the GPs' attitudes, awareness, and practice regarding early diagnosis of dementia. RESULTS: Specific screening tests or protocols to diagnose and manage dementia were not used by 53% of our GPs. The training on the recognition of early AD signs and symptoms was considered inadequate by 55% of the participants. Females were more likely to consider their training insufficient (58%) compared to males (53%). Female GPs were less likely to prescribe antipsychotic drugs to control neuropsychiatric symptoms (NPS) and suggest specialist advice in late stage of cognitive impairment. Multiple Correspondence Analysis (MCA) performed only on GP QUAD suggested two dimensions explaining 26.1% ("GP attitude") and 20.1% ("GP knowledge") of the inertia for a total of 46.2%, CONCLUSION: In our survey on GP clinical practice, several problems in properly recognizing early AD symptoms and subsequently screening patients to be referred to secondary/tertiary care centers for diagnosis confirmation have emerged. In the future, specific training programs and educational projects for GPs should be implemented also in Italy to improve detection rates and management of dementia in primary care. PMID- 26817512 TI - Prognostic and Therapeutic Implications of MicroRNA in Malignant Pleural Mesothelioma. AB - Malignant Pleural Mesothelioma (MPM) is an aggressive disease characterized by a dismal prognosis, mainly due to late diagnosis. To date, there are very few treatment options available and the refractoriness to the majority of therapeutic strategies, leading to consider MPM a relevant problem in public health. Therefore, the identification of novel prognostic markers and alternative therapeutic strategies remain a top priority. Several efforts have been made in this direction and to date a number of studies have investigated the role of microRNA as biomarkers in MPM, identifying the potential prognostic role of miR 29c* and miR-31. Very recently, the first microRNA signature able to discriminate poor or and good prognosis of MPM patients underwent surgery has been published. Very interestingly, several microRNA such as miR-1, miR-16, and miR-34b/c have been identified as potential therapeutic agents. Indeed, the forced expression of these microRNA resulted in anti-tumor effects both in vitro and in vivo. Besides, the introduction of microRNA mimic, some agents such as EphrinA1 and Onconase, seemed to exert anti-tumor effects through specific microRNA. Moreover, microRNA have also been reported to play a role in chemoresistance enhancing the sensitivity to specific drug such as pemetrexed. In this review the most relevant and updated data about the role of microRNA as prognostic markers and therapeutic agents in MPM will be presented, opening new avenues towards improved management of this aggressive disease. PMID- 26817513 TI - Predictability of the dispersion of Fukushima-derived radionuclides and their homogenization in the atmosphere. AB - Long-range simulation of the dispersion of air pollutants in the atmosphere is one of the most challenging tasks in geosciences. Application of precise and fast numerical models in risk management and decision support can save human lives and can diminish consequences of an accidental release. Disaster at Fukushima Daiichi nuclear power plant has been the most serious event in the nuclear technology and industry in the recent years. We present and discuss the results of the numerical simulations on dispersion of Fukushima-derived particulate (131)I and (137)Cs using a global scale Lagrangian particle model. We compare concentrations and arrival times, using two emission scenarios, with the measured data obtained from 182 monitoring stations located all over the Northern Hemisphere. We also investigate the homogenization of isotopes in the atmosphere. Peak concentrations were predicted with typical accuracy of one order of magnitude showing a general underestimation in the case of (131)I but not for (137)Cs. Tropical and Arctic plumes, as well as the early detections in American and European midlatitudes were generally well predicted, however, the later regional-scale mixing could not be captured by the model. Our investigation highlights the importance of the parameterization of free atmospheric turbulence. PMID- 26817514 TI - Microbial diversity drives multifunctionality in terrestrial ecosystems. AB - Despite the importance of microbial communities for ecosystem services and human welfare, the relationship between microbial diversity and multiple ecosystem functions and services (that is, multifunctionality) at the global scale has yet to be evaluated. Here we use two independent, large-scale databases with contrasting geographic coverage (from 78 global drylands and from 179 locations across Scotland, respectively), and report that soil microbial diversity positively relates to multifunctionality in terrestrial ecosystems. The direct positive effects of microbial diversity were maintained even when accounting simultaneously for multiple multifunctionality drivers (climate, soil abiotic factors and spatial predictors). Our findings provide empirical evidence that any loss in microbial diversity will likely reduce multifunctionality, negatively impacting the provision of services such as climate regulation, soil fertility and food and fibre production by terrestrial ecosystems. PMID- 26817515 TI - Female reproductive competition explains variation in prenatal investment in wild banded mongooses. AB - Female intrasexual competition is intense in cooperatively breeding species where offspring compete locally for resources and helpers. In mammals, females have been proposed to adjust prenatal investment according to the intensity of competition in the postnatal environment (a form of 'predictive adaptive response'; PAR). We carried out a test of this hypothesis using ultrasound scanning of wild female banded mongooses in Uganda. In this species multiple females give birth together to a communal litter, and all females breed regularly from one year old. Total prenatal investment (size times the number of fetuses) increased with the number of potential female breeders in the group. This relationship was driven by fetus size rather than number. The response to competition was particularly strong in low weight females and when ecological conditions were poor. Increased prenatal investment did not trade off against maternal survival. In fact we found the opposite relationship: females with greater levels of prenatal investment had elevated postnatal maternal survival. Our results support the hypothesis that mammalian prenatal development is responsive to the intensity of postnatal competition. Understanding whether these responses are adaptive requires information on the long-term consequences of prenatal investment for offspring fitness. PMID- 26817516 TI - Ferroelectricity and Self-Polarization in Ultrathin Relaxor Ferroelectric Films. AB - We report ferroelectricity and self-polarization in the (001) oriented ultrathin relaxor ferroelectric PMN-PT films grown on Nb-SrTiO3, SrRuO3 and La0.7Sr0.3MnO3, respectively. Resistance-voltage measurements and AC impedance analysis suggest that at high temperatures Schottky depletion width in a 4 nm thick PMN-PT film deposited on Nb-SrTiO3 is smaller than the film thickness. We propose that Schottky interfacial dipoles make the dipoles of the nanometer-sized polar nanoregions (PNRs) in PMN-PT films grown on Nb-SrTiO3 point downward at high temperatures and lead to the self-polarization at room temperature with the assistance of in-plane compressive strain. This work sheds light on the understanding of epitaxial strain effects on relaxor ferroelectric films and self polarization mechanism. PMID- 26817518 TI - Investigating the Role of Helicobacter pylori PriA Protein. AB - BACKGROUND: In bacteria, PriA protein, a conserved DEXH-type DNA helicase, plays a central role in replication restart at stalled replication forks. Its unique DNA binding property allows it to recognize and stabilize stalled forks and the structures derived from them. PriA plays a very critical role in replication fork stabilization and DNA repair in E. coli and N. gonorrhoeae. In our in vivo expression technology screen, priA gene was induced in vivo when Helicobacter pylori infects mouse stomach. MATERIALS AND METHODS: We decided to elucidate the role of H. pylori PriA protein in survival in mouse stomach, survival in gastric epithelial cells and macrophage cells, DNA repair, acid stress, and oxidative stress. RESULTS: The priA null mutant strain was unable to colonize mice stomach mucosa after long-term infections. Mouse colonization was observed after 1 week of infection, but the levels were much lower than the wild-type HpSS1 strain. PriA protein was found to be important for intracellular survival of epithelial cell-/macrophage cell-ingested H. pylori. Also, a priA null mutant was more sensitive to DNA-damaging agents and was much more sensitive to acid and oxidative stress as compared to the wild-type strain. CONCLUSIONS: These data suggest that the PriA protein is needed for survival and persistence of H. pylori in mice stomach mucosa. PMID- 26817517 TI - Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis. AB - Crystals cause injury in numerous disorders, and induce inflammation via the NLRP3 inflammasome, however, it remains unclear how crystals induce cell death. Here we report that crystals of calcium oxalate, monosodium urate, calcium pyrophosphate dihydrate and cystine trigger caspase-independent cell death in five different cell types, which is blocked by necrostatin-1. RNA interference for receptor-interacting protein kinase 3 (RIPK3) or mixed lineage kinase domain like (MLKL), two core proteins of the necroptosis pathway, blocks crystal cytotoxicity. Consistent with this, deficiency of RIPK3 or MLKL prevents oxalate crystal-induced acute kidney injury. The related tissue inflammation drives TNF alpha-related necroptosis. Also in human oxalate crystal-related acute kidney injury, dying tubular cells stain positive for phosphorylated MLKL. Furthermore, necrostatin-1 and necrosulfonamide, an inhibitor for human MLKL suppress crystal induced cell death in human renal progenitor cells. Together, TNF-alpha/TNFR1, RIPK1, RIPK3 and MLKL are molecular targets to limit crystal-induced cytotoxicity, tissue injury and organ failure. PMID- 26817519 TI - Subcellular localization of calcium deposits in the noble crayfish Astacus astacus spermatophore: Implications for post-mating spermatophore hardening and spermatozoon maturation. AB - The freshly ejaculated spermatophore of crayfish undergoes a hardening process during post-mating storage on the body surface of female. The ultrastructural distribution of calcium deposits were studied and compared in freshly ejaculated and post-mating noble crayfish spermatophores, using the oxalate-pyroantimonate technique, to determine possible roles of calcium in post-mating spermatophore hardening and spermatozoon maturation. Small particles of sparsely distributed calcium deposits were visible in the wall of freshly ejaculated spermatophore. Also, large amount of calcium deposits were visible in the membranes of the freshly ejaculated spermatozoon. Five minutes post-ejaculation, granules in the spermatophore wall appeared as porous formations with numerous electron lucent spaces. Calcium deposits were visible within the spaces and scattered in the spermatophore wall matrix, where smaller calcium deposits combined to form globular calcium deposits. Large numbers of the globular calcium deposits were visible in the wall of the post-mating spermatophore. Smaller calcium deposits were detected in the central area of post-mating spermatophore, which contains the sperm mass, and in the extracellular matrix and capsule. While the density of calcium deposits decreased in the post-mating spermatozoon membranes, numerous small calcium deposits appeared in the subacrosomal zone and nucleus. Substantial changes in calcium deposit distribution in the crayfish spermatophore during post mating storage on the body of female may be involved in the processes of the spermatophore hardening and spermatozoon maturation. PMID- 26817520 TI - Population demographics of American eels Anguilla rostrata in two Arkansas, U.S.A., catchments that drain into the Gulf of Mexico. AB - The goal of this study was to compare American eel Anguilla rostrata life history in two inland river systems in Arkansas, U.S.A., that ultimately discharge into the Gulf of Mexico via the Mississippi River and the Red-Atchafalaya catchments. From 21 June 2011 to 24 April 2014, 238 yellow-phase A. rostrata were captured in the middle Ouachita River and tributaries using boat electrofishing and 39 in the lower White River using multiple sampling gears. Most of them were caught downstream of dams in both basins (61%). Medium-sized A. rostrata ranging from 225 to 350 mm total length (LT ) were the most abundant size group in the Ouachita River basin, but they were absent from the White River. Mean LT at age 4 years (i.e. youngest shared age) was 150 mm greater for the White River than the Ouachita River basin. Anguilla rostrata appeared to have a greater initial LT (i.e. minimum size upon arrival) in the White River that allowed them to reach a gonado-somatic index (IG ) of 1.5 up to 4 years earlier, and downstream migration appeared to occur 5 years earlier at 100 mm greater LT ; these differences may be related to increased river fragmentation by dams in the Ouachita River basin. Growth and maturation of A. rostrata in this study were more similar to southern populations along the Atlantic coast than other inland populations. Adult swimbladder nematodes Anguillicoloides crassus were not present in any of the 214 swimbladders inspected. Gulf of Mexico catchments may be valuable production areas for A. rostrata and data from these systems should be considered as range wide protection and management plans are being developed. PMID- 26817522 TI - ANZJOG in 2016: Passing the baton. PMID- 26817521 TI - PAI-1, a target gene of miR-143, regulates invasion and metastasis by upregulating MMP-13 expression of human osteosarcoma. AB - Despite recent improvements in the therapy for osteosarcoma, 30-40% of osteosarcoma patients die of this disease, mainly due to its lung metastasis. We have previously reported that intravenous injection of miR-143 significantly suppresses lung metastasis of human osteosarcoma cells (143B) in a mouse model. In this study, we examined the biological role and mechanism of miR-143 in the metastasis of human osteosarcoma cells. We identified plasminogen activator inhibitor-1 (PAI-1) as a direct target gene of miR-143. To determine the role of PAI-1 in human osteosarcoma cells, siRNA was transfected into 143B cells for knockdown of PAI-1 expression. An in vitro study showed that downregulation of PAI-1 suppressed cell invasion activity, but not proliferation. Moreover, injection of PAI-1 siRNA into a primary lesion in the osteosarcoma mouse model inhibited lung metastasis compared to control siRNA-injected mice, without influencing the proliferative activity of the tumor cells. Subsequent examination using 143B cells revealed that knockdown of PAI-1 expression resulted in downregulation of the expression and secretion of matrix metalloproteinase-13 (MMP-13), which is also a target gene of miR-143 and a proteolytic enzyme that regulates tumor-induced osteolysis. Immunohistochemical analysis using clinical samples showed that higher miR-143 expressing cases showed poor expression of PAI 1 in the primary tumor cells. All such cases belonged to the lung metastasis negative group. Moreover, the frequency of lung metastasis-positive cases was significantly higher in PAI-1 and MMP-13 double-positive cases than in PAI-1 or MMP-13 single-positive or double-negative cases (P < 0.05). These results indicated that PAI-1, a target gene of miR-143, regulates invasion and lung metastasis via enhancement of MMP-13 expression and secretion in human osteosarcoma cells, suggesting that these molecules could be potential therapeutic target genes for preventing lung metastasis in osteosarcoma patients. PMID- 26817523 TI - Noninvasive prenatal testing in routine clinical practice--an audit of NIPT and combined first-trimester screening in an unselected Australian population. AB - BACKGROUND: There are limited data regarding noninvasive prenatal testing (NIPT) in low-risk populations, and the ideal aneuploidy screening model for a pregnant population has yet to be established. AIMS: To assess the implementation of NIPT into clinical practice utilising both first- and second-line screening models. MATERIALS AND METHODS: Three private practices specialising in obstetric ultrasound and prenatal diagnosis in Australia offered NIPT as a first-line test, ideally followed by combined first-trimester screening (cFTS), or as a second line test following cFTS, particularly in those with a calculated risk between 1:50 and 1:1000. RESULTS: NIPT screening was performed in 5267 women and as a first-line screening method in 3359 (63.8%). Trisomies 21 and 13 detection was 100% and 88% for trisomy 18. Of cases with known karyotypes, the positive predictive value (PPV) of the test was highest for trisomy 21 (97.7%) and lowest for monosomy X (25%). Ultrasound detection of fetal structural abnormality resulted in the detection of five additional chromosome abnormalities, two of which had high-risk cFTS results. For all chromosomal abnormalities, NIPT alone detected 93.4%, a contingent model detected 81.8% (P = 0.097), and cFTS alone detected 65.9% (P < 0.005). CONCLUSIONS: NIPT achieved 100% T21 detection and had a higher DR of all aneuploidy when used as a first-line test. Given the false positive rate for all aneuploidies, NIPT is an advanced screening test, rather than a diagnostic test. The benefit of additional cFTS was the detection of fetal structural abnormalities and some unusual chromosomal abnormalities. PMID- 26817524 TI - Alterations in energy homeostasis to favour adipose tissue gain: A longitudinal study in healthy pregnant women. AB - BACKGROUND: Pregnancy is associated with an increase in body fat; however, excessive gestational weight gain predisposes to significant maternal and neonatal morbidity and mortality. It remains unclear whether alterations in energy homeostasis have a major influence on fat storage. AIMS: To evaluate longitudinal changes in body composition and energy metabolism in healthy pregnant women. MATERIALS AND METHODS: Body composition, energy expenditure and energy intake were measured longitudinally in 26 women with singleton pregnancies at 12-14 weeks, 24-26 weeks and 34-36 weeks of gestation. Fat mass (FM) and lean body mass (LBM) were measured using bio-impedance analysis, total energy expenditure (TEE) using the Sensewear Armband and energy intake through a 3-day food recall diary. RESULTS: Throughout pregnancy, all women remained healthy. Body weight increased by 10.8 +/- 3.9 kg, from 67.3 +/- 14.1 kg to 78.1 +/- 13.8 kg from the first to the third trimester (P < 0.001). Body fat percentage increased by 4.5 +/- 4.2% (P < 0.001). LBM also increased throughout pregnancy, by 3.9 +/- 2.4 kg (P < 0.001). TEE increased significantly from the first to the third trimesters (9514 kJ/day to 10 263 kJ/day; P < 0.05). In contrast, energy expenditure due to physical activity, energy intake and macronutrient intake did not change significantly throughout pregnancy. CONCLUSION: Healthy women increase FM during pregnancy despite slight increases in TEE and no change in energy intake. This suggests that energy storage efficiency improves during pregnancy, which may be related to alterations in gut microbiota and activation of anabolic pathways during pregnancy. Clarifying factors leading to this more efficient fat and energy storing state, and the role of the pregnancy-related changes in gut microbiota, may be important for managing gestational weight gain. PMID- 26817525 TI - Role of oral tramadol 50 mg in reducing pain associated with outpatient hysteroscopy: A randomised double-blind placebo-controlled trial. AB - BACKGROUND: Several drugs have been used to reduce hysteroscopy-associated pain. Although the Royal College of Obstetricians and Gynaecologists has recommended against the use of opiates in outpatient hysteroscopy, we wished to investigate if opioids can be used if the appropriate opioid was given in the appropriate dose. AIM: To study the effectiveness of tramadol 50 mg in reducing pain associated with outpatient hysteroscopy. MATERIALS AND METHODS: A prospective randomised double-blind placebo-controlled trial conducted in the outpatient hysteroscopy clinic at Cairo University Hospital. Main outcome measures were the severity of pain during the procedure, immediately after the procedure and 30 minutes later assessed by a visual analogue scale (VAS). VAS of 0 indicates no pain and VAS of 10 indicates the worst possible pain. RESULTS: A total of 140 women who had diagnostic outpatient hysteroscopy were randomised to receive oral tramadol 50 mg or placebo one h before performing outpatient hysteroscopy. There was no difference between the groups in the age, parity, duration of the procedures or indications of hysteroscopy. The median pain score was significantly lower in the tramadol group during the procedure (5 vs 6; P = 0.013), immediately after the procedure (3 vs 4; P < 0.036), and 30 minute later (1 vs 2; P = 0.034). Two women in the tramadol group reported nausea, but this was mild and did not warrant cancelling the procedure. CONCLUSIONS: Oral administration of tramadol 50 mg before hysteroscopy reduces the pain evoked by the procedure and the drug was well tolerated by women. PMID- 26817526 TI - Is there a difference in the behaviour and subsequent management of ectopic pregnancies seen at first scan compared to those ectopic pregnancies which commence as pregnancies of unknown location? AB - AIMS: The primary aim was to assess whether ectopic pregnancies (EPs) visualised on primary scan behave differently to EPs initially characterised as pregnancies of unknown location (PUL). The secondary aim was to assess whether the EP group is more likely to have surgical management compared to the PUL ectopic pregnancy group. MATERIALS AND METHODS: Prospective observational study. Consecutive first trimester women presenting from November 2006 to March 2012 underwent transvaginal ultrasound (TVS). Women diagnosed with an EP on TVS were divided into two groups: visualised EPs noted on the first TVS, and PULs which subsequently developed into EPs. Twenty-five historical, clinical, biochemical and ultrasonographic variables were collected. Different management strategies (expectant, medical, surgical) once an EP was confirmed on TVS were recorded. Univariate analysis was performed to compare differences between the two groups as well as rates for the three final management strategies. RESULTS: A total of 3341 consecutive women underwent TVS. On initial scan, 86.2% were classified as intrauterine pregnancy, 8.8% as PUL and 5.0% as EP (145 tubal/23 nontubal EPs). There were 194 tubal EPs in final analysis: 49 of 194 (25.3%) initially classified as PUL and 145 of 194 (74.7%) diagnosed as EP at primary TVS. When comparing the EP to the PUL EP group, the pain scores were 3.34 versus 1.91 (P value < 0.001), the mean sac diameters were 35.2 versus 18.5 mm (P-value = 0.0327), and the volume of the EP masses were 8.21E+04 versus 1.40E+04 (P-value = 0.0341). Cumulative surgical intervention rate was significantly higher in EP compared to PUL EP group (P-value = 0.036). CONCLUSIONS: EPs seen at the first ultrasound scan appear to be more symptomatic, larger in diameter and volume compared to EPs which started as PULs. Cumulative surgical intervention rate was noted to be higher in this group with EP seen on ultrasound at the outset. PMID- 26817527 TI - Insertion of the Bakri balloon: The earlier, the better? PMID- 26817528 TI - Corrigendum. AB - The authors of the following manuscript would like to draw the reader's attention to an error in the article: de Costa C, Douglas H, Hamblin J, Ramsay P, and Shircore M. Abortion law across Australia - A review of nine jurisdictions. Aust N Z J Obstet Gynaecol 2015; 55: 105-111. In this article, Table 1 should be replaced as shown below. The authors apologise for this error and any confusion it may have caused. PMID- 26817529 TI - The responses of immune cells to iron oxide nanoparticles. AB - Immune cells play an important role in recognizing and removing foreign objects, such as nanoparticles. Among various parameters, surface coatings of nanoparticles are the first contact with biological system, which critically affect nanoparticle interactions. Here, surface coating effects on nanoparticle cellular uptake, toxicity and ability to trigger immune response were evaluated on a human monocyte cell line using iron oxide nanoparticles. The cells were treated with nanoparticles of three types of coatings (negatively charged polyacrylic acid, positively charged polyethylenimine and neutral polyethylene glycol). The cells were treated at various nanoparticle concentrations (5, 10, 20, 30, 50 MUg ml(-1) or 2, 4, 8, 12, 20 MUg cm(-2)) with 6 h incubation or treated at a nanoparticle concentration of 50 MUg ml(-1) (20 MUg cm(-2)) at different incubation times (6, 12, 24, 48 or 72 h). Cell viability over 80% was observed for all nanoparticle treatment experiments, regardless of surface coatings, nanoparticle concentrations and incubation times. The much lower cell viability for cells treated with free ligands (e.g. ~10% for polyethylenimine) suggested that the surface coatings were tightly attached to the nanoparticle surfaces. The immune responses of cells to nanoparticles were evaluated by quantifying the expression of toll-like receptor 2 and tumor necrosis factor alpha. The expression of tumor necrosis factor-alpha and toll-like receptor 2 were not significant in any case of the surface coatings, nanoparticle concentrations and incubation times. These results provide useful information to select nanoparticle surface coatings for biological and biomedical applications. PMID- 26817530 TI - Gas-Phase Infrared Spectroscopy of Substituted Cyanobutadiynes: Roles of the Bromine Atom and Methyl Group as Substituents. AB - The IR spectra of 5-bromo-2,4-pentadiynenitrile (Br-C=C-C=C-CN) and 2,4 hexadiynenitrile (CH3 -C=C-C=C-CN), a compound of interstellar interest, have been recorded within the 4000-500 cm(-1) spectral region and calculated by means of high-level ab initio and density functional calculations. Although the calculated structures of both compounds are rather similar, there are very subtle differences, mainly in the strength of the C=C bond not directly bound to the substituent. These subtle bonding differences are reflected in small, but not negligible, differences in the electron density at the corresponding bond critical points, and, more importantly, are reflected in the IR spectra. Indeed, the IR spectrum for the bromine derivative presents two well-differentiated strong bands around 2250 cm(-1) , whereas for the methyl derivative both absorptions coalesce in a single band. These bands correspond in both cases to the coupling between C=C and C=N stretching displacements. A third, very weak, band also associated with C=C and C=N coupled stretches is observed for the bromine derivative, but not for the methyl one, owing to its extremely low intensity. PMID- 26817531 TI - alpha-Amino Acid-Isosteric alpha-Amino Tetrazoles. AB - The synthesis of all 20 common natural proteinogenic and 4 otheralpha-amino acid isosteric alpha-amino tetrazoles has been accomplished, whereby the carboxyl group is replaced by the isosteric 5-tetrazolyl group. The short process involves the use of the key Ugi tetrazole reaction followed by deprotection chemistries. The tetrazole group is bioisosteric to the carboxylic acid and is widely used in medicinal chemistry and drug design. Surprisingly, several of the common alpha amino acid-isosteric alpha-amino tetrazoles are unknown up to now. Therefore a rapid synthetic access to this compound class and non-natural derivatives is of high interest to advance the field. PMID- 26817532 TI - Effects of selected herbicides and fungicides on growth, sporulation and conidial germination of entomopathogenic fungus Beauveria bassiana. AB - BACKGROUND: The in vitro fungicidal effects of six commonly used fungicides, namely fluazinam, propineb, copper(II) hydroxide, metiram, chlorothalonil and mancozeb, and herbicides, namely isoxaflutole, fluazifop-P-butyl, flurochloridone, foramsulfuron, pendimethalin and prosulfocarb, on mycelial growth, sporulation and conidial germination of entomopathogenic fungus Beauveria bassiana (ATCC 74040) were investigated. Mycelial growth rates and sporulation at 15 and 25 degrees C were evaluated on PDA plates containing 100, 75, 50, 25, 12.5, 6.25 and 0% of the recommended application rate of each pesticide. The tested pesticides were classified in four scoring categories based on reduction in mycelial growth and sporulation. RESULTS: All pesticides, herbicides and fungicides tested had fungistatic effects of varying intensity, depending on their rate in the medium, on B. bassiana. The most inhibitory herbicides were flurochloridone and prosulfocarb, and fluazinam and copper(II) hydroxide were most inhibitory among the fungicides, while the least inhibitory were isoxaflutole and chlorothalonil. Sporulation and conidial germination of B. bassiana were significantly inhibited by all tested pesticides compared with the control treatment. Flurochloridone, foramsulfuron, prosulfocarb and copper(II) hydroxide inhibited sporulation entirely at 100% rate (99-100% inhibition), and the lowest inhibition was shown by fluazifop-P-butyl (22%) and metiram (33%). At 100% dosage, all herbicides in the test showed a high inhibitory effect on conidial germination. Conidial germination inhibition ranged from 82% with isoxaflutole to 100% with fluorochloridone, pendimethalin and prosulfocarb. At 200% dosage, inhibition rates even increased (96-100%). CONCLUSIONS: All 12 pesticides tested had a fungistatic effect on B. bassiana of varying intensity, depending on the pesticide and its concentration. B. bassiana is highly affected by some herbicides and fungicides even at very low rates. Flurochloridone, foramsulfuron, prosulfocarb and copper(II) hydroxide stopped sporulation. Of all tested pesticides, isoxaflutole, fluazifop-P-butyl and chlorothalonil showed the least adverse effects and therefore probably could be compatible with B. bassiana in the field. (c) 2016 Society of Chemical Industry. PMID- 26817534 TI - Gun Violence as a Public Health Problem. PMID- 26817533 TI - Effect of levodopa-carbidopa intestinal gel on dyskinesia in advanced Parkinson's disease patients. AB - OBJECTIVE: The purpose of this study was to assess the effect of levodopa carbidopa intestinal gel (carbidopa-levodopa enteral suspension) in advanced Parkinson's disease patients with troublesome dyskinesia. METHODS: Post hoc analyses of patient data from a 12-week, randomized, double-blind study and a 54 week open-label study were performed. Efficacy was assessed in the subgroup of patients defined by >=1 hour of "on" time with troublesome dyskinesia at baseline as recorded in Parkinson's disease symptom diaries (double blind: n = 11 levodopa carbidopa intestinal gel, n = 12 oral levodopa-carbidopa; open label: n = 144 levodopa-carbidopa intestinal gel). The changes in "off" time, "on" time with and without troublesome dyskinesia, and the overall safety and tolerability of levodopa-carbidopa intestinal gel were analyzed. RESULTS: Although not significantly different from oral levodopa treatment (P > .05) in the double blind study, levodopa-carbidopa intestinal gel treatment resulted in a reduction from baseline in "on" time with troublesome dyskinesia (mean [standard deviation] hours: baseline = 3.1 [1.7], change from baseline to final = -1.8 [1.8], P = .014), increase in "on" time without troublesome dyskinesia (baseline = 7.4 [2.2], change = 4.4 [3.6], P = .004), and decrease in "off" time (baseline = 5.5 [1.3], change = -2.7 [2.8], P = .015). Similar trends were found in the open label study. An increase in levodopa-carbidopa intestinal gel dose was not significantly correlated with increased "on" time with troublesome dyskinesia in either study (double blind: r = -.073, P = .842; open label: r = -0.001, P = .992). Adverse events were usually mild to moderate in severity and related to the gastrointestinal procedure. CONCLUSION: Our exploratory analyses suggest that optimizing levodopa delivery with levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson's disease. PMID- 26817535 TI - Nurses on a Different Front Line. PMID- 26817537 TI - Nurses With Disabilities. PMID- 26817538 TI - VA Nurses' Overtime Lawsuit to Move Forward. AB - Maintaining electronic health records after hours has long gone unpaid. PMID- 26817540 TI - CDC Advisory Warns of Possible Nationwide Increase in Fentanyl Deaths. AB - Improved detection and expanded use of naloxone are recommended. PMID- 26817545 TI - Hospitals Evolve into Community Health Networks. AB - Nurses are playing a vital role in the shift from in-patient care to community based health. PMID- 26817548 TI - Alpha-2 Agonists for Long-Term Sedation During Mechanical Ventilation in Critically Ill Patients. PMID- 26817552 TI - Latino Nurses in the United States: An Overview of Three Decades (1980-2010). AB - OBJECTIVE: This study aims to provide demographic data on the 5.4% of U.S. RNs who are Latino in order to assist nursing educators in planning more effective engagement with the growing U.S. Latino population. METHODS: Detailed data from the U.S. Census for the years 1980 to 2010 were used to identify the total U.S. population and the total number of RNs in four standard U.S. Census racial and ethnic groups: non-Latino white (NLW), Latino, African American, and Asian/Pacific Islander. RESULTS: The number of RNs in each racial or ethnic group per 100,000 persons of that same group is reported for all four groups. Spanish language ability and nativity were derived only for the NLW and Latino groups. Data are reported for the United States as a whole and for the five states with the largest Latino populations: California, Florida, Illinois, New York, and Texas. Of the four racial and ethnic groups, Latinos had the fewest number of RNs per 100,000 population in the period from 1980 to 2010. Compared with NLW RNs, Latino RNs were more likely to speak Spanish and to have been born abroad. State by-state variations from the national patterns are provided. CONCLUSIONS: While major nursing organizations have expressed a desire to increase the diversity of the nursing workforce, the data show that Latinos lag far behind all other racial and ethnic groups in representation among RNs. Nursing education programs and institutions need to improve their efforts to increase the number of Latino nurses relative to the Latino population. PMID- 26817556 TI - A Task Force to Address Bullying. AB - Bullying in the workplace can create a dysfunctional environment that is associated with serious physical and psychological harm to the person being bullied. Nurses' experience with bullying has gained considerable attention in recent years, and warrants further discussion. Nurse leaders need to develop and implement effective bullying prevention initiatives that will foster the functioning of a professional and productive staff in a healthy work environment. The aim of this article is to review workplace bullying as experienced by nurses, and describe how nurses at a Magnet-designated academic medical center developed and implemented a bullying task force to address the problem. PMID- 26817557 TI - 'An Immutably Personal Process': A Hospice Nurse Contemplates Uncontrol. PMID- 26817558 TI - Lessons Learned from Litigation: Discrimination Against Nurses. AB - What if a patient doesn't want to be cared for by a provider against whom the patient harbors a personal bias? PMID- 26817563 TI - Partnering with the Police. AB - A nurse-led initiative trains law enforcement to effectively interact with people with mental illness. PMID- 26817564 TI - A New Antibiotic. PMID- 26817565 TI - The Multifaceted Actions of Leukaemia Inhibitory Factor in Mediating Uterine Receptivity and Embryo Implantation. AB - Embryo implantation is mediated by the combined actions of the ovarian hormones E2 and P4 on the uterus. In addition, the pro-inflammatory cytokine, leukaemia inhibitory factor (LIF), plays a pivotal role in regulating uterine receptivity. LIF is expressed in the endometrial glands and has a robust action on the uterine luminal epithelium (LE). In mice, LIF is induced by nidatory E2 and functions to convert the LE from a non-receptive to an embryo-responsive state. LIF mediates its actions by activating the JAK-STAT pathway specifically in the LE. Activation of JAK-STAT pathway results in the induction of many additional pathways, including some 40 + transcription factors, many of which initiate a cascade of changes affecting epithelial polarity, epithelial-mesenchymal interactions, angiogenesis, stromal cell decidualization, and inhibiting cell proliferation. This review discusses the role of LIF and the recent analysis of its action on the uterine LE in regulating endometrial receptivity and implantation. PMID- 26817566 TI - How do I get my manuscript accepted? Steps and missteps. PMID- 26817568 TI - Hypertriglyceridemia, remnant cholesterol and cardiovascular risk: what genes can say. PMID- 26817570 TI - Body composition changes in acute stroke by type of feeding regimen. PMID- 26817567 TI - Fibromyalgia: management strategies for primary care providers. AB - AIMS: Fibromyalgia (FM), a chronic disorder defined by widespread pain, often accompanied by fatigue and sleep disturbance, affects up to one in 20 patients in primary care. Although most patients with FM are managed in primary care, diagnosis and treatment continue to present a challenge, and patients are often referred to specialists. Furthermore, the lack of a clear patient pathway often results in patients being passed from specialist to specialist, exhaustive investigations, prescription of multiple drugs to treat different symptoms, delays in diagnosis, increased disability and increased healthcare resource utilisation. We will discuss the current and evolving understanding of FM, and recommend improvements in the management and treatment of FM, highlighting the role of the primary care physician, and the place of the medical home in FM management. METHODS: We reviewed the epidemiology, pathophysiology and management of FM by searching PubMed and references from relevant articles, and selected articles on the basis of quality, relevance to the illness and importance in illustrating current management pathways and the potential for future improvements. RESULTS: The implementation of a framework for chronic pain management in primary care would limit unnecessary, time-consuming, and costly tests, reduce diagnostic delay and improve patient outcomes. DISCUSSION: The patient-centred medical home (PCMH), a management framework that has been successfully implemented in other chronic diseases, might improve the care of patients with FM in primary care, by bringing together a team of professionals with a range of skills and training. CONCLUSION: Although there remain several barriers to overcome, implementation of a PCMH would allow patients with FM, like those with other chronic conditions, to be successfully managed in the primary care setting. PMID- 26817569 TI - Enterococcal bloodstream infection. Design and validation of a mortality prediction rule. AB - BACKGROUND: To develop a prediction rule to describe the risk of death as a result of enterococcal bloodstream infection. METHODS: A prediction rule was developed by analysing data collected from 122 patients diagnosed with enterococcal BSI admitted to the Clinica Universidad de Navarra (Pamplona, Spain); and validated by confirming its accuracy with the data of an external population (Hospital del Mar, Barcelona). RESULTS: According to this model, independent significant predictors for the risk of death were being diabetic, have received appropriate treatment, severe prognosis of the underlying diseases, have renal failure, received solid organ transplant, malignancy, source of the bloodstream infection and be immunosuppressed. The prediction rule showed a very good calibration (Hosmer-Lemeshow statistic, P = 0.93) and discrimination for both training and testing sets (area under ROC curve = 0.84 and 0.83 respectively). CONCLUSIONS: The predictive rule was able to predict risk of death as a result of enterococcal bloodstream infection as well as to identify patients, who being below the threshold value, will have a low risk of death with a negative predictive value of 96%. PMID- 26817571 TI - Comparison of two cohorts of women who expulsed either a copper-intrauterine device or a levonorgestrel-releasing intrauterine system. AB - AIM: To assess if there is a difference in the characteristics of the women who expelled a copper-intrauterine device (TCu-IUD) or the levonorgestrel-releasing intrauterine system (LNG-IUS) and the frequency of expulsions over different periods of observation. METHODS: We retrospectively analyzed 19 697 medical charts of women consulting between January 1980 and December 2013 who requested a TCu-IUD or a LNG-IUS. RESULTS: The medical records of 17 644 Cu-IUD and 2053 LNG IUS users returning to the clinic for a follow-up visit after insertion of an IUC were reviewed. Of these, 1532 Cu-IUD and 254 LNG-IUS parous users were found to have expelled the IUC for a first time. The mean age at insertion (+/- standard deviation) was 26.3 +/- 6.6 years (range 16-49) for Cu-IUD users and 31.7 +/- 7.6 years (range 18-48) for LNG-IUS users (P < 0.001). A total of 263 (13.4%) and 12 (4.3%) of the Cu-IUD and the LNG-IUS users were <=19 years old, and 49.1% and 54.1% of the expulsions among the Cu-IUD and LNG-IUS users, respectively, were reported in the first six months after placement. A regression model showed that the variables significantly associated with an expulsion of either a Cu-IUD or LNG-IUS were age < 25 years, less than two deliveries and using a Cu-IUD. CONCLUSION: Our findings showed that the characteristics associated with IUC expulsion were age under 25 years, having had less than two deliveries and being users of Cu-IUD. PMID- 26817572 TI - Moderately elevated maternal homocysteine at preconception is inversely associated with cognitive performance in children 4 months and 6 years after birth. AB - Prenatal methyl donor deficiency leads to homocysteine accumulation in the brain and impaired neurodevelopment in rats. We investigated the effect of moderately elevated preconception fasting total plasma homocysteine (tHcy) on child neurodevelopment in a prospective study of 67 and 76 mother-child pairs at 4 months and 6 years of age, respectively. Fasting blood samples at 2-10 weeks preconception, from the cord (nonfasting) and the mother and child 6 years after birth, were collected. Psychomotor and mental development were assessed at 4 months using the Bayley Scale of Infant Development (BSID) and cognitive development at 6 years using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI). Highest tertile preconception tHcy (>=9.04 umol/L) was categorized as moderately elevated and low-mid tertile tHcy as normal. Children, born to mothers with moderately elevated compared to normal preconception tHcy, scored lower [mean (95% CI)] in the BSID psychomotor [115 (105, 124) vs. 126 (121, 130), p = 0.03] and mental [101 (93, 109) vs. 113 (107, 119), p = 0.03] development tests. Multiple logistic regression analysis showed that moderately elevated compared to normal preconception tHcy was associated with greater probability, OR (95%CI), of scoring in the lowest tertile for BSID psychomotor development (<=120): 4.0 (1.1, 14.3) and lowest tertiles for WPPSI full (<=111), verbal (<=104) and performance (<=111), intellectual quotient: 6.0 (1.5, 23.7), 3.5 (1.1, 11.2) and 4.1 (1.1, 15.7), respectively. We conclude that moderately elevated preconception tHcy is inversely associated with psychomotor and cognitive development scores in infants and children. PMID- 26817573 TI - Factors Predicting Mobility and the Change in Activities of Daily Living After Hip Fracture: A 1-Year Prospective Cohort Study. AB - OBJECTIVES: To assess the change in ambulatory ability, need for walking aids, and activities of daily living (ADL) after femoral neck, intertrochanteric, or subtrochanteric fractures and to examine the determinants of these functional outcomes. DESIGN: A prospective observational cohort study. SETTING: A multicenter study involving 1 university hospital and 2 community hospitals. PATIENTS: A consecutive cohort of 552 patients (mean age, 78.3 years; range, 50 105) who underwent surgery for a hip fracture. MAIN OUTCOME MEASURES: Ambulatory ability, need for walking aids, and ADL index, 4 and 12 months after surgery. RESULTS: At both 4 months and 1-year follow-up time points, there was a significant decrease in ambulatory ability and the ADL index score and also an increase in the need for walking aids in comparison with the prefracture status. Ambulatory ability, but not ADL, significantly recovered between the 4-month and 1-year follow-up. One year after fracture, the prefracture functional status was regained by 57% of the patients, but approximately 13% of the formerly ambulating patients were unable to walk. The prefracture status was the most important determinant of ambulatory ability, need for walking aids, and ADL. Comorbidities, a poor cognitive status, and non-weight-bearing status after surgery were also negative predictors. Neither the fracture pattern nor its specific surgical treatment was predictive of any functional outcomes. CONCLUSIONS: Regardless of the type of fracture or surgical treatment used, 57% of the patients do not regain their prefracture ambulatory ability. Recovery of ambulatory ability can occur until 1 year postoperatively. The prefracture status and cognitive level are the most important determinant of all functional outcomes. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence. PMID- 26817574 TI - Endosteal Biologic Augmentation for Surgical Fixation of Displaced Femoral Neck Fractures. AB - OBJECTIVES: To report outcomes of a cohort with displaced femoral neck fractures (FNFs) treated with a length/angle-stable construct augmented with an endosteal fibular allograft serving as a biologic dowel. DESIGN: Prospective. SETTING: Level I Trauma Center. PATIENTS: The study group consists of 27 patients with isolated FNF surgically treated by a single surgeon. INTERVENTION: Open reduction of the femoral neck, fixed with a length- and angle-stable construct of 2 fully threaded cannulated screws augmented with an endosteal fibular allograft serving as a biologic dowel. MAIN OUTCOME MEASUREMENTS: Clinical and radiographic outcomes of the fixation construct and the viability of both the femoral head and the fibular allograft, host response to the allograft and osseous union were evaluated using a specialized sequence of contrast-enhanced magnetic resonance imaging (MRI) obtained at 3 and 12 months postoperatively. RESULTS: This construct resulted in high union rates (89%; 24 of 27). Two patients suffered early catastrophic failure and 1 patient developed fracture nonunion, all of wish underwent uneventful conversion to total hip arthroplasty. Three additional patients (11%) had removal of symptomatic implants. The clinical and radiographic outcomes were excellent. Twelve-month MRIs revealed either partial or complete osseous incorporation of 86% the fibular allografts without signs of adverse reaction of the host to the allograft. Femoral head osteonecrosis segments were noted in 76% of patients on MRI; however, radiographically, there were no signs of osteonecrosis or segmental collapse. CONCLUSIONS: The fibular allograft reconstructs the comminuted femoral neck, and the osteointegration overtime increases the strength of the host bone-graft interface. This added strength seems to provide the stability needed to better preserve the intraoperative reduction, obtain good outcomes, and reduce the complications associated with FNF. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 26817575 TI - Prescription of Vitamin D to Fracture Patients: A Lack of Consensus and Evidence. AB - OBJECTIVES: We conducted a survey to explore practice patterns regarding the assessment of hypovitaminosis D and the prescription of vitamin D in acute fracture patients. Our secondary objective was to determine whether practice patterns differed between fragility and nonfragility fracture patients. DESIGN: Cross-sectional survey. SETTING: All surveys were completed using SurveyMonkey. PATIENTS/PARTICIPANTS: We surveyed surgeon members of the Canadian Orthopaedic Association and the Orthopaedic Trauma Association. INTERVENTION: Survey. MAIN OUTCOME MEASUREMENTS: The proportion of surgeons who routinely prescribe vitamin D to fracture patients. RESULTS: A total of 397 surveys were completed. Of total, 65.8% of surgeons indicated that they routinely prescribe vitamin D to fragility fracture patients and 25.7% routinely prescribe vitamin D to nonfragility fracture patients. We identified considerable variability in dosing regimens, as 45 different dosing regimens were prescribed in fragility fracture patients and 29 in nonfragility fracture patients. They ranged from daily doses of 400 IU to loading doses of 600,000 IU. The most frequently prescribed doses were 1000 IU daily (14.6%), 2000 IU daily (13.4%), and 50,000 IU weekly (8.7%). Respondents indicated that they heavily relied on clinical experience to guide their decisions to prescribe vitamin D to fracture patients. CONCLUSIONS: The results of this survey demonstrate multiple areas of uncertainty and a lack of consensus in the prescription of vitamin D to fracture patients. Fragility patients frequently receive vitamin D supplementation, whereas most surgeons do not prescribe vitamin D to young fracture patients. High-quality clinical research is needed to determine whether vitamin D supplementation is beneficial to fracture patients. LEVEL OF EVIDENCE: Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence. PMID- 26817576 TI - Synthesis, characterization, and biological evaluation of new biotinylated (99m) Tc/Re-tricarbonyl complexes. AB - The synthesis and biological evaluation of three new biotinylated fac [(99m)Tc/Re(CO)3](+) complexes with the tridentate ligands L1, L2, and L3 are reported. L1-L3 contain the chelators 2-((5-aminopentyl)(pyridin-2 ylmethyl)amino)acetic acid, 2-(2-aminoethylthio)-3-(1H-imidazol-4-yl)propanoic acid, and 2-amino-3-(1-carboxy-2-(1H-imidazol-4-yl)ethylthio)propanoic acid, respectively, which are conjugated to biotin's carboxylate via their amine group. The fac-[Re(CO)3(L1-L3)] complexes were synthesized and characterized by NMR and IR, where the (N,N,O) coordination for ReL1 and the (N,S,O) coordination for ReL2 and ReL3 were confirmed. The tracer complexes fac-[(99m)Tc(CO)3(L1-L3)] were synthesized in high yield and were found highly stable in 10(-3) M L-histidine and L-cysteine over 24 h. Furthermore, they exhibited high binding affinity (>90%) for avidin. Rat plasma studies showed complete cleavage of biotin from (99m)TcL1 after 1 h and a low percentage of intact (99m)TcL2 and (99m)TcL3 with no biotin cleavage metabolites present, over 24 h. Similarly, rat urine analysis showed the presence of intact (99m)TcL2 and (99m)TcL3, while (99m)TcL1 was cleaved. Biodistribution studies of (99m)TcL2 and (99m)TcL3 revealed fast blood and tissue clearance. PMID- 26817577 TI - Protective capacity of cercarial transformation fluid alone or in combination with crude cercarial antigen against challenge infections of Schistosoma mansoni in mice. AB - Schistosomiasis is the second major parasitic disease in the world after malaria. It affects 201.5 million cases in Africa alone. The aim of this research was to explore alternative vaccination strategies against experimental schistosomiasis mansoni. We assessed the effect of cercarial transformation fluid (CTF) singly and in combination with crude cercarial antigen (CCA) using alum as an adjuvant. The combined antigens gave the best results, as evidenced by a significant reduction in the worm load (62.07%), tissue egg count (78.16%, 86.46%) in liver and intestine respectively, and hepatic granuloma size (29.96%). Scanning electron microscopy revealed changes in the tegument, in the form of roughness and appearance of vesicles and furrows between the tegumental tubercles. Also, resorption of the ventral sucker and dimples replacing its spines were observed. The female tegument was irregular and its posterior end showed loss of spines and sensory bulbs. Moreover, there was a significant decrease in liver enzymes (alanine transaminase (ALT) and aspartate transaminase (AST)) compared to infected control mice. A significant elevation in CD4+T-lymphocytes, denoting amelioration of the immune status, in mice that received combined antigens was also observed. It can be concluded that combined antigens demonstrate potential as a vaccine against Schistosoma mansoni. PMID- 26817578 TI - Blockage of ultrafast and directional diffusion of Li atoms on phosphorene with intrinsic defects. AB - The diffusion of Li in electrode materials is a key factor for the charging/discharging rate capacity of a Li-ion battery (LIB). Recently, two dimensional phosphorene has been proposed as a very promising electrode material due to its ultrafast and directional lithium diffusion, as well as large energy capacity. Herein, on the basis of density functional theory, we report that intrinsic point defects, including vacancy and stone-wales defects, will block the directional ultrafast diffusion of lithium in phosphorene. On the defect-free phosphorene, diffusion of Li along the zig-zag lattice direction is 1.6 billion times faster than along the armchair lattice direction, and 260 times faster than that in graphite. After introducing intrinsic vacancy and stone-wales defect, the diffusion energy barrier of Li along the zig-zag lattice direction increases sharply to the range of 0.17-0.49 eV, which blocks the ultrafast migration of lithium along the zig-zag lattice direction. Moreover, the open circuit voltage increases with the emergence of defects, which is not suitable for anode materials. In addition, the formation energies of the defects in phosphorene are considerably lower than those in graphene and silicene sheet; therefore, it is highly important to generate defect-free phosphorene for LIB applications. PMID- 26817579 TI - Bacterial diversity in the surface sediments of the hypoxic zone near the Changjiang Estuary and in the East China Sea. AB - Changjiang (Yangtze River) Estuary has experienced severe hypoxia since the 1950s. In order to investigate potential ecological functions of key microorganisms in relation to hypoxia, we performed 16S rRNA-based Illumina Miseq sequencing to explore the bacterial diversity in the surface sediments of the hypoxic zone near the Changjiang Estuary and in the East China Sea (ECS). The results showed that numerous Proteobacteria-affiliated sequences in the sediments of the inner continental shelf were related to both sulfate-reducing and sulfur oxidizing bacteria, suggesting an active sulfur cycle in this area. Many sequences retrieved from the hypoxic zone were also related to Planctomycetes from two marine upwelling systems, which may be involved in the initial breakdown of sulfated heteropolysaccharides. Bacteroidetes, which is expected to degrade high-molecular-weight organic matter, was abundant in all the studied stations except for station A8, which was the deepest and possessed the largest grain size. In addition, dissolved organic carbon, water depth, percentage ratio of clay to silt, salinity, and sedimentary grain size were environmental effectors that shaped the sedimentary microbial community structure. Our results showed that putative Gammaproteobacteria-affiliated sulfur-oxidizing bacteria may not only detoxify hydrogen sulfide produced by sulfate-reducing prokaryotes, but also serve as the primary producers in the marine sediments. Specific groups of aerobic Bacteroidetes and Planctomycetes participated in degrading organic matter, which might contribute to the oxygen depletion in the hypoxic zones. PMID- 26817580 TI - Combination of the Manifold Dimensionality Reduction Methods with Least Squares Support vector machines for Classifying the Species of Sorghum Seeds. AB - This study was carried out for rapid and noninvasive determination of the class of sorghum species by using the manifold dimensionality reduction (MDR) method and the nonlinear regression method of least squares support vector machines (LS SVM) combing with the mid-infrared spectroscopy (MIRS) techniques. The methods of Durbin and Run test of augmented partial residual plot (APaRP) were performed to diagnose the nonlinearity of the raw spectral data. The nonlinear MDR methods of isometric feature mapping (ISOMAP), local linear embedding, laplacian eigenmaps and local tangent space alignment, as well as the linear MDR methods of principle component analysis and metric multidimensional scaling were employed to extract the feature variables. The extracted characteristic variables were utilized as the input of LS-SVM and established the relationship between the spectra and the target attributes. The mean average precision (MAP) scores and prediction accuracy were respectively used to evaluate the performance of models. The prediction results showed that the ISOMAP-LS-SVM model obtained the best classification performance, where the MAP scores and prediction accuracy were 0.947 and 92.86%, respectively. It can be concluded that the ISOMAP-LS-SVM model combined with the MIRS technique has the potential of classifying the species of sorghum in a reasonable accuracy. PMID- 26817581 TI - Increase in frequencies of circulating Th-17 cells correlates with microbial translocation, immune activation and exhaustion in HIV-1 infected patients with poor CD4 T-cell reconstitution. AB - We analyzed the association of circulating Th-17 cells (cTh-17) with immune activation (IA), immune exhaustion (IE) and regulatory T-cells (T-regs) in 20 human immunodeficiency virus-1 (HIV-1) infected patients with impaired restoration of CD4 T-cell counts despite prolonged suppression of plasma viremia (discordant) and compared it with 20 HIV-1 infected patients showing good immunologic and virologic responses (concordant) following highly active antiretroviral therapy (HAART). Discordant HIV-1 infected patients showed significantly higher frequencies of cTh-17 cells compared to concordant patients and healthy controls after PMA+Ionomicin stimulation. Discordant patients also showed higher CD4 T-cell immune activation (HLA-DR+CD38+) than concordant patients which directly correlated with microbial translocation. Additionally, CD4 T-cells of discordant patients showed higher frequencies of CD4 T-cells expressing multiple immune exhaustion markers (Tim3+PD-1+) which correlated with immune activation indicating that combined analysis of inhibitory molecules along with PD-1 might be a better predictor for immune exhaustion of CD4 T-cells. Increased cTh-17 cell frequency correlated inversely with CD4 T-cell percentages and absolute counts and directly with CD4 T-cell immune activation and T-reg frequencies. Persistent CD4 T-cell immune activation might favor differentiation of activated CD4 T-cells toward cTh-17 phenotype in discordant patients. Discordant patients had significantly lower baseline CD4 T-cell counts and higher viral load at the initiation of HAART and higher immune activation and immune exhaustion after being on HAART for long time indicating that these factors might be associated with an increase in cTh-17 cell frequency, thus, increasing the risk of disease progression despite virologic control. PMID- 26817582 TI - Factors associated with return to work in men and women with work-related traumatic brain injury. AB - BACKGROUND: Symptoms that persist subsequent to a work-related traumatic brain injury (wrTBI) influence the ability to return to work (RTW) and indicate areas of functional disability, as classified in the International Classification of Functioning, Disability and Health (ICF) framework. OBJECTIVE: The purpose of this study was to describe the relationship between RTW status and ICF framework domains in men and women with a wrTBI. METHODS: A retrospective chart review of 209 consecutive workers with TBI (mild TBI: 71.8%; mean age: 40.2 +/- 11.1, men: 71.3%) was conducted. Workers were assessed during the chronic post-injury phase, at the neurology service of a large rehabilitation hospital in Ontario, Canada in 2003. Frequency distributions were calculated and chi-square tests performed. RESULTS: At the point of assessment, 78.0% of workers were in receipt of disability benefits, while the remainder had returned to work on a full- or part time basis. Significant differences were observed in the Body Functions and Structures domain of the ICF model, specifically clinical diagnoses of depression, anxiety, pain disorders; self-perceived cognitive disturbance, and certain psychosocial factors (p < 0.05), between workers who had returned to work and those who had not. When stratified according to sex, these associations remained significant only in men. CONCLUSIONS: The factors outlined above should be subject to further TBI research, as indicators for RTW. The lack of significant findings in women warrants further exploration of variables within the physical and social environmental domains of the ICF. PMID- 26817583 TI - Are biologics useful for nail psoriasis? AB - Apart from involving skin, psoriasis can compromise the nails and adjacent structures. Even though there are multiple therapeutic alternatives, there is great interest in biological therapy, but no consensus on its role exists. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including three randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded it is not clear whether biological therapy is superior to placebo in the treatment of nail psoriasis because the certainty of the evidence is very low. PMID- 26817585 TI - Correlation between Hierarchical Structure and Processing Control of Large-area Spray-coated Polymer Solar Cells toward High Performance. AB - The formation mechanism of a spray-coated film is different from that of a spin coated film. This study employs grazing incidence small- and wide-angle X-ray Scattering (GISAXS and GIWAXS, respectively) quantitatively and systematically to investigate the hierarchical structure and phase-separated behavior of a spray deposited blend film. The formation of PCBM clusters involves mutual interactions with both the P3HT crystal domains and droplet boundary. The processing control and the formed hierarchical structure of the active layer in the spray-coated polymer/fullerene blend film are compared to those in the spin-coated film. How the different post-treatments, such as thermal and solvent vapor annealing, tailor the hierarchical structure of the spray-coated films is quantitatively studied. Finally, the relationship between the processing control and tailored BHJ structures and the performance of polymer solar cell devices is established here, taking into account the evolution of the device area from 1 * 0.3 and 1 * 1 cm(2). The formation and control of the special networks formed by the PCBM cluster and P3HT crystallites, respectively, are related to the droplet boundary. These structures are favorable for the transverse transport of electrons and holes. PMID- 26817584 TI - MiR-130a-3p regulates cell migration and invasion via inhibition of Smad4 in gemcitabine resistant hepatoma cells. AB - BACKGROUND: Emerging evidence demonstrates that microRNAs (miRNAs) play an important role in regulation of cell growth, invasion and metastasis through inhibiting the expression of their targets. It has been reported that miR-130a-3p controls cell growth, migration and invasion in a variety of cancer cells. However, it is unclear whether miR-130a-3p regulates epithelial-mesenchymal transition (EMT) in drug resistant cancer cells. Therefore, in the current study, we explore the role and molecular mechanisms of miR-130a-3p in gemcitabine resistant (GR) hepatocellular carcinoma (HCC) cells. METHODS: The real-time RT PCR was used to measure the miR-130a-3p expression in GR HCC cells compared with their parental cells. The wound healing assay was conducted to determine the cell migratory activity in GR HCC cells treated with miR-130a-3p mimics. The migration and invasion assays were also performed to explore the role of miR-130a-3p in GR HCC cells. Western blotting analysis was used to measure the expression of Smad4, E-cadherin, Vimentin, and MMP-2 in GR HCC cells after depletion of Smad4. The luciferase assay was conducted to validate whether Smad4 is a target of miR-130a 3p. The student t-test was used to analyze our data. RESULTS: We found the down regulation of miR-130a-3p in GR HCC cells. Moreover, we validate the Smad4 as a potential target of miR-130a-3p. Furthermore, overexpression of miR-130a-3p suppressed Smad4 expression, whereas inhibition of miR-130a-3p increased Smad4 expression. Consistently, overexpression of miR-130a-3p or down-regulation of Smad4 suppressed the cell detachment, attachment, migration, and invasion in GR HCC cells. CONCLUSIONS: Our findings provide a molecular insight on understanding drug resistance in HCC cells. Therefore, activation of miR-130a-3p or inactivation of Smad4 could be a novel approach for the treatment of HCC. PMID- 26817586 TI - Early Molecular Events in Murine Gastric Epithelial Cells Mediated by Helicobacter pylori CagA. AB - BACKGROUND: Murine models of Helicobacter pylori infection are used to study host pathogen interactions, but lack of severe gastritis in this model has limited its usefulness in studying pathogenesis. We compared the murine gastric epithelial cell line GSM06 to the human gastric epithelial AGS cell line to determine whether similar events occur when cultured with H. pylori. MATERIALS AND METHODS: The lysates of cells infected with H. pylori isolates or an isogenic cagA deficient mutant were assessed for translocation and phosphorylation of CagA and for activation of stress pathway kinases by immunoblot. RESULTS: Phosphorylated CagA was detected in both cell lines within 60 minutes. Phospho-ERK 1/2 was present within several minutes and distinctly present in GSM06 cells at 60 minutes. Similar results were obtained for phospho-JNK, although the 54 kDa phosphoprotein signal was dominant in AGS, whereas the lower molecular weight band was dominant in GSM06 cells. CONCLUSION: These results demonstrate that early events in H. pylori pathogenesis occur within mouse epithelial cells similar to human cells and therefore support the use of the mouse model for the study of acute CagA-associated host cell responses. These results also indicate that reduced disease in H. pylori-infected mice may be due to lack of the Cag PAI, or by differences in the mouse response downstream of the initial activation events. PMID- 26817587 TI - Tungiasis-associated morbidity in pigs and dogs in endemic villages of Uganda. AB - BACKGROUND: Tunga penetrans (Insecta, Siphonaptera, Tungidae) causes severe morbidity among heavily infected humans and animals in Latin America and sub Saharan Africa. The clinical pathology of tungiasis in animals has never been studied systematically. METHODS: This was a cross-sectional study conducted between January to March 2015, aimed at describing tungiasis-associated clinical pathology in 121 and 20 T. penetrans-infected pigs and dogs, living in nine and five endemic rural villages respectively located in Bugiri District, Busoga, Uganda. RESULTS: The parasite load of infected animals ranged from one to 246 (median 8) and one to eight (median 2) in pigs and dogs, respectively. In pigs 99.3% and in dogs 100% of the lesions were located on feet. In pigs, hind legs were significantly more affected than front legs (90.9% vs. 57.9%; p = 0.002) and also had more lesions than the front legs (median 5 vs. 1; p = 0.0001). However, in dogs localization of lesions between front and hind legs never differed significantly (front, 50% vs. hind, 65%; p = 0.51) and so were the number of lesions (median front = 0.5 vs. median hind = 2; p = 0.7). Acute and chronic clinical pathology coexisted. The most common disease manifestations in pigs were hoof wall erosions (68.6%), tissue necrosis of hoof wall and skin (66.1), pain at infection sites (47.9%), hoof deformity (45.5%), fissures (44.6%) and edema (44.6%). In dogs, tungiasis mainly presented with pain at attachment site (80%), ulcers (55%), necrosis (30%) as well as hyperemia and edema (both 15%). One pig had lost dew claws while two had loose detaching claws. Despite a lower number of sand fleas, a higher proportion of infected dogs (20%) than pigs (5.8%) exhibited functional limb use difficulties (p = 0.05). CONCLUSIONS: The pattern of clinical manifestations in pigs and dogs were very similar to those reported from affected humans and rats. The important morbidity associated with animal tungiasis makes the disease a serious veterinary health problem in sub-Saharan Africa warranting treatment and control for optimal animal production. PMID- 26817589 TI - One of the Challenges of Bringing Your Newborn Home Begins with Installing the Car Safety Seat. PMID- 26817588 TI - Physicians' Perceptions of Shared Decision Making in Chronic Disease and Its Barriers and Facilitators. AB - This study assessed pediatric physicians' use of shared decision making (SDM) in 2 chronic conditions. Most physicians indicated that parent and adolescent trust and emotional readiness facilitated SDM, physicians' preferred approach to decision making. At the same time, they perceived few barriers, other than insurance limitations, to using SDM. PMID- 26817590 TI - Heliotrope Rash and Gottron Papules in a Child with Juvenile Dermatomyositis. PMID- 26817591 TI - Fructose-Rich Beverage Intake and Central Adiposity, Uric Acid, and Pediatric Insulin Resistance. AB - OBJECTIVE: To determine the association between sugar-sweetened beverage (SSB) consumption with biomarkers of insulin resistance (IR) and investigate whether/how this relates to obesity and serum uric acid in adolescents. STUDY DESIGN: Adolescents (n = 1454, aged 12-16 years) were assessed in a study conducted to monitor Multilevel Risk Profiles for Adolescent Metabolic Syndrome in Taiwan. Detailed information about demographics, diet, physical, anthropometric, and clinical variables was collected. An original homeostatic model assessment of IR (HOMA1-IR), updated nonlinear homeostatic model assessment of IR (HOMA2-IR) model, and several IR markers were measured. RESULTS: Adolescents who consumed a greater amount of SSBs were more likely to have elevated fasting serum insulin, HOMA1-IR, and HOMA2-IR (P for trends, <=.028). Compared with SSB nondrinkers, those with >350 mL/d intake of heavy high-fructose corn syrup-containing SSBs had a 0.52 and 0.30 higher multivariate-adjusted HOMA1 IR and HOMA2-IR, respectively. Waist circumference and serum uric acid were correspondingly found to explain 25.4% and 23.6%, as well as 23.2% and 20.6%, of the increases in the 2 IR markers. Both the elevations of HOMA1-IR and HOMA2-IR for high-fructose corn syrup-rich SSB intake were strengthened among obese adolescents (P for interaction, <=.033). CONCLUSIONS: Fructose-rich SSB intake is associated with elevated levels of IR, and this relationship may be partially mediated by central adiposity and serum uric acid. Obesity may modify the effect of this type of SSB consumption in intensifying the elevation of IR in adolescents. PMID- 26817592 TI - Simple lines and shapes are associated with, and communicate, distinct emotions. AB - We investigated whether lines and shapes that present face-like features would be associated with emotions. In Experiment 1, participants associated concave, convex, or straight lines with the words happy or sad. Participants found it easiest to associate the concave line with happy and the convex line with sad. In Experiment 2, participants rated (valence, pleasantness, liking, and tension) and categorised (valence and emotion words) two convex and concave lines that were paired with six distinct pairs of eyes. The presence of eyes affected participants' valence ratings and response latencies; more congruent eye-mouth matches produced more consistent ratings and faster reaction times. In Experiment 3, we examined whether dots that resembled eyes would be associated with emotional words. Participants found it easier to match certain sets of dots with specific emotions. These results suggest that facial gestures that are associated with specific emotions can be captured using relatively simple shapes and lines. PMID- 26817593 TI - Two novel MU6-O(2-) bridged Co14/Ni14 hydroxamate clusters packed in distorted face-centered cubic patterns. AB - Two novel clusters [Co(MU6-O(2-))(sbha)12(sba)2 (DMF)7(DMA)].(DMF)8 (1) and [Ni(MU6-O(2-))(sbha)12(sba)2(DMF)8] (2) (sH2bha = 4-bromo-benzohydroximic acid; sHba = 4-bromobenzene carboxylic acid; DMF = N,N-dimethylformamide; DMA = dimethylamine) have been synthesized. The novel body-centred MU6-O(2-) bridged Co14 and Ni14 clusters are packed in distorted face-centered cubic (FCC) patterns with different symmetries. Magnetic studies confirmed the antiferromagnetic exchange interactions between magnetic centers. PMID- 26817594 TI - Sensitivity and specificity of the Gastrointestinal Short Form Questionnaire in diagnosis of gastroesophageal reflux disease. AB - INTRODUCTION: Gastrointestinal Short Form Questionnaire (GSFQ) is a questionnaire for gastroesophageal reflux disease (GERD) diagnosis, with a version in Spanish language, not yet compared to an objective test. AIMS: To establish GSFQ diagnostic performance against 24-hour pH monitoring carried out in two tertiary care hospitals. METHODS: Consecutive adult patients with typical GERD symptoms (heartburn, regurgitation) referred for pH monitoring fulfilled the GSFQ (score range 0-30, proportional to probability of GERD). Diagnosis of GERD was established when acid exposure time in distal esophagus was superior to 4.5% or symptom association probability was greater than 95%. Receiver-operator characteristic (ROC) curves were calculated and best cut-off score determined, with corresponding sensitivity, specificity and likelihood ratios (LR) (95% confidence interval for each). RESULTS: One hundred and fifty-two patients were included (59.9% women, age 47.9 +/- 13.9; 97.4% heartburn; 71.3% regurgitation). pH monitoring was abnormal in 65.8%. Mean GSFQ score was 11.2 +/- 6. Area under ROC was 56.5% (47.0-65.9%). Optimal cut-off score was 13 or greater: sensitivity 40% (30.3-50.3%), specificity 71.2% (56.9-82.9%), positive LR 1.39 (0.85-2.26) and negative LR 0.84 (0.67-1.07). Exclusion of questions 1 and 3 of the original GSFQ, easily interpreted as referred to dyspepsia and not GERD, improved only marginally the diagnostic performance: AUROC 59.1%. CONCLUSION: The GSFQ does not predict results of pH monitoring in patients with typical symptoms in a tertiary care setting. PMID- 26817595 TI - Estimated pulmonary capillary wedge pressure assessed by speckle tracking echocardiography predicts successful ablation in paroxysmal atrial fibrillation. AB - BACKGROUND: Atrial fibrillation (AF) is associated with left atrial (LA) remodeling caused by pressure and/or volume (LAV) overload. Increased pulmonary capillary wedge pressure (PCWP) represents LA pressure overload. We recently reported that pulmonary capillary wedge pressure (ePCWP) can be estimated by the kinetics-tracking (KT) index that combines LA function and volume using speckle tracking echocardiography (STE), and has a strong correlation with PCWP measured by right heart catheterization (r = 0.92). Therefore, we hypothesized that ePCWP is the best echocardiographic predictor of successful AF ablation. METHODS: We enrolled 137 patients with paroxysmal AF (age: 61 +/- 10 years) who underwent pulmonary vein isolation. We measured LAV index, LA emptying function (EF) and LA stiffness during sinus rhythm before ablation using STE. PCWP was noninvasively estimated by STE as we previously reported. Parameters were compared between a group with AF recurrence (n = 30, age: 59 +/- 11 years) and a group with successful ablation (sinus rhythm maintained for >1 year) (n = 107, age 61 +/- 11 years). RESULTS: The ePCWP was correlated with PCWP measured by right heart catheterization (r = 0.76, p < 0.01). Compared with the non-recurrence group (n = 107, age: 61 +/- 11), the AF recurrence group had significantly increased ePCWP (10.6 +/- 3.5 vs 14.6 +/- 2.9 mmHg, p < 0.01), minimum LAV index (29 +/- 12 ml/m(2) vs 37 +/- 14 ml/m(2), p < 0.01) and LA stiffness (0.47 +/- 0.33 vs 0.83 +/- 0.59, p < 0.01), but lower total LA EF (44 +/- 11% vs 39 +/- 13%, p < 0.01) before ablation. In multivariate logistic regression analysis, ePCWP was the most significant independent predictor of successful ablation. Using 13 mmHg of PCWP as the optimal cutoff value, the sensitivity and specificity for successful ablation were 73 and 77% (area under the curve = 0.81), respectively. CONCLUSION: The ePCWP that is measured by the combination of LA function and volume before ablation was a better predictor of the successful ablation compared with LA function and volume separately. The ePCWP estimated by STE is useful to predict the successful ablation in paroxysmal AF, and could be useful to improve candidate selection for AF ablation. PMID- 26817596 TI - Arabidopsis Motif Scanner. AB - BACKGROUND: The major mechanism driving cellular differentiation and organism development is the regulation of gene expression. Cis-acting enhancers and silencers have key roles in controlling gene transcription. The genomic era allowed the transition from single gene analysis to the investigation of full transcriptomes. This transition increased the complexity of the analyses and the difficulty in the interpretation of the results. In this context, there is demand for new tools aimed at the creation of gene networks that can facilitate the interpretation of Next Generation Sequencing (NGS) data. RESULTS: Arabidopsis Motif Scanner (AMS) is a Windows application that runs on local computers. It was developed to build gene networks by identifying the positions of cis-regulatory elements in the model plant Arabidopsis thaliana and by providing an easy interface to assess and evaluate gene relationships. Its major innovative feature is to combine the cis-regulatory element positions, NGS and DNA Chip Arrays expression data, Arabidopsis annotations and gene interactions for the identification of gene networks regulated by transcription factors. In studies focused on transcription factors function, the software uses the expression data and binding site motifs in the regulative gene regions to predict direct target genes. Additionally, AMS utilizes DNA-protein and protein-protein interaction data to facilitate the identification of the metabolic pathways regulated by the transcription factor of interest. CONCLUSIONS: Arabidopsis Motif Scanner is a new tool that helps researchers to unravel gene relations and functions. In fact, it facilitates studies focused on the effects and the impact that transcription factors have on the transcriptome by correlating the position of cis-acting elements, gene expression data and interactions. PMID- 26817597 TI - Asian expert recommendation on management of skin and mucosal effects of radiation, with or without the addition of cetuximab or chemotherapy, in treatment of head and neck squamous cell carcinoma. AB - With increasing numbers of patients with unresectable locoregionally advanced (LA) head and neck squamous cell carcinoma (HNSCC) receiving cetuximab/radiotherapy (RT), several guidelines on the early detection and management of skin-related toxicities have been developed. Considering the existing management guidelines for these treatment-induced conditions, clinical applicability and standardization of grading methods has remained a cause of concern globally, particularly in Asian countries. In this study, we attempted to collate the literature and clinical experience across Asian countries to compile a practical and implementable set of recommendations for Asian oncologists to manage skin- and mucosa-related toxicities arising from different types of radiation, with or without the addition of cetuximab or chemotherapy. In December 2013, an international panel of experts in the field of head and neck cancer management assembled for an Asia-Pacific head and neck cancer expert panel meeting in China. The compilation of discussion outcomes of this meeting and literature data ultimately led to the development of a set of recommendations for physicians with regards to the approach and management of dermatological conditions arising from RT, chemotherapy/RT and cetuximab/RT, and similarly for the approach and management of mucositis resulting from RT, with or without the addition of chemotherapy or cetuximab. These recommendations helped to adapt guidelines published in the literature or text books into bedside practice, and may also serve as a starting point for developing individual institutional side effect management protocols with adequate training and education. PMID- 26817598 TI - Percutaneous transcatheter snare vegetectomy in a child. AB - Surgical vegetectomy may be indicated in patients with unresolving sepsis, heart failure, recurrent embolism, or the presence of large vegetations >10 mm in size. Percutaneous vegetectomy using a snare may be a reasonable option instead of open heart surgery in selected patients. We describe the case of a patient with operated tetralogy of Fallot and infective endocarditis who underwent vegetectomy via a percutaneous approach. PMID- 26817599 TI - Impact of metabolic syndrome and its components on heart rate variability during hemodialysis: a cross-sectional study. AB - BACKGROUND: Both uremia and metabolic syndrome (MetS) affect heart rate variability (HRV) which is a risk factor of poor prognoses. The aim of this study was to evaluate the impact of MetS on HRV among chronic hemodialysis patients. METHODS: This cross-sectional study was carried out in a teaching hospital in Northern Taiwan from June to August, 2010. Adult patients on chronic hemodialysis without active medical conditions were enrolled. HRV were measured for 4 times on the index hemodialysis day (HRV-0, -1, -2, and -3 at before, initial, middle, and late phases of hemodialysis, respectively), and the baseline demographic data and clinical parameters during the hemodialysis session were documented. Then we evaluated the impacts of MetS and its five components on HRV. RESULTS: One hundred and seventy-five patients (100 women, mean age 65.1 +/- 12.9 years) were enrolled and included those with MetS (n = 91, 52 %) and without MetS (n = 84, 48 %). The patients with MetS(+) had significantly lower very low frequency, total power, and variance in HRV-0, total power and variance in HRV-2, and variance in HRV-3. (all p ? 0.05) When using the individual components of MetS to evaluate the impacts on HRV indices, the fasting plasma glucose (FPG) criterion significantly affected most indices of HRV while other four components including "waist circumference", "triglycerides", "blood pressure", and "high-density lipoprotein" criteria exhibited little impacts on HRV. FPG criterion carried the most powerful influence on cardiac ANS, which was even higher than that of MetS. The HRV of patients with FPG(+) increased initially during the hemodialysis, but turned to decrease dramatically at the late phase of hemodialysis. CONCLUSIONS: The impact of FPG(+) outstood the influence of uremic autonomic dysfunction, and FPG criterion was the most important one among all the components of MetS to influence HRV. These results underscored the importance of interpretation and management for abnormal glucose metabolism. PMID- 26817600 TI - Psychological and personality factors in type 2 diabetes mellitus, presenting the rationale and exploratory results from The Maastricht Study, a population-based cohort study. AB - BACKGROUND: Strong longitudinal evidence exists that psychological distress is associated with a high morbidity and mortality risk in type 2 diabetes. Little is known about the biological and behavioral mechanisms that may explain this association. Moreover, the role of personality traits in these associations is still unclear. In this paper, we first describe the design of the psychological part of The Maastricht Study that aims to elucidate these mechanisms. Next, we present exploratory results on the prevalence of depression, anxiety and personality traits in type 2 diabetes. Finally, we briefly discuss the importance of these findings for clinical research and practice. METHODS: We measured psychological distress and depression using the MINI diagnostic interview, the PHQ-9 and GAD-7 questionnaires in the first 864 participants of The Maastricht Study, a large, population-based cohort study. Personality traits were measured by the DS14 and Big Five personality questionnaires. Type 2 diabetes was assessed by an oral glucose tolerance test. Logistic regression analyses were used to estimate the associations of depression, anxiety and personality with type 2 diabetes, adjusted for age, sex and education level. RESULTS: Individuals with type 2 diabetes had higher levels of depressive and anxiety symptoms, odds ratios (95 % CI) were 3.15 (1.49; 6.67), 1.73 (0.83-3.60), 1.50 (0.72-3.12), for PHQ-9 >= 10, current depressive disorder and GAD-7 >= 10, respectively. Type D personality, social inhibition and negative affectivity were more prevalent in type 2 diabetes, odds ratios were 1.95 (1.23-3.10), 1.35 (0.93-1.94) and 1.70 (1.14-2.51), respectively. Individuals with type 2 diabetes were less extraverted, less conscientious, less agreeable and less emotionally stable, and similar in openness to individuals without type 2 diabetes, although effect sizes were small. CONCLUSIONS: Individuals with type 2 diabetes experience more psychological distress and have different personality traits compared to individuals without type 2 diabetes. Future longitudinal analyses within The Maastricht Study will increase our understanding of biological and behavioral mechanisms that link psychological distress to morbidity and mortality in type 2 diabetes. PMID- 26817601 TI - Antimicrobial, antioxidant, toxicity and phytochemical assessment of extracts from Acmella uliginosa, a leafy-vegetable consumed in Benin, West Africa. AB - BACKGROUND: Acmella uliginosa (Asteraceae) is a flowering plant whose leaves are consumed as a vegetable in Benin. They are also traditionally used as an antibiotic in the treatment of infectious diseases. To evaluate the therapeutic potential and toxicity effect of this leafy-vegetable, the antibacterial, antifungal, antioxidant activities and, toxicity and phytochemical constituents were investigated. METHODS: Dichloromethane, methanol and aqueous extracts of Acmella uliginosa were evaluated for their antimicrobial activity against six bacterial and six fungi strains. Antibacterial and antifungal activities were investigated by microdilution method and agar diffusion method respectively. Antioxidant activity was assessed using the 2,2-diphenyl-1-picryl-hydrazyl assay and phytochemical screening was carried out using standard procedures. Finally, oral acute toxicity at a dose of 2000 mg/kg was done according to the Organization for Economic Co-operation and Development guideline n degrees 423. RESULTS: The antibacterial activity was broad spectrum, inhibiting both Gram positive and Gram-negative bacteria. The minimum inhibitory concentration ranged from 0.625 to 5 mg/ml. The antifungal evaluation show that all the extracts inhibited mycelial growth and sporulation of fungi with percentages of inhibition ranging from 9.39 to 75.67% and 22.04 to 99.77%, respectively. In DPPH radical scavenging assay, the effect on reducing free radicals increased in a dose dependent manner. The percentage of inhibition of DPPH ranged from 0.94 to 73.07%. Phytochemical screening revealed the presence of coumarin, flavonoid, naphtoquinone, anthracene derivative, saponin, lignan, triterpene and tannin. The dichloromethane and methanol extracts showed the best biological activities; they were also shown as the best extraction solvents of phytochemicals. In the acute toxicity evaluation, all animals were physically active and no deaths of rats were observed during the test. However, the aqueous extract promoted biochemical, hematological and histopathological alterations of treated rats at 2000 mg/kg body weight. CONCLUSION: A. uliginosa extracts contains antimicrobial, antioxidant agents and was not lethal for rats when ingested. However, according to the results obtained for biochemical, hematological, and histopathological analysis, caution is required regarding its consumption. PMID- 26817602 TI - Emerging drugs targeting human epidermal growth factor receptor 2 (HER2) in the treatment of breast cancer. AB - INTRODUCTION: Human epidermal growth factor 2 (HER2) overexpression is present in 20% of breast cancer patients. It is associated with more aggressive disease and worse clinical outcome. New drugs are thus needed. Approved and future treatments will be discussed in this review. AREAS COVERED: The monoclonal antibodies trastuzumab and pertuzumab, the tyrosine kinase inhibitor lapatinib and the antibody-drug conjugate trastuzmab emtansine are approved for HER2 positive breast cancer. The combination of trastuzumab, pertuzumab and docetaxel is currently the first-line treatment in the metastatic setting. New therapies are still needed due to frequent relapse and resistance. These include mammalian target of rapamycin inhibitors, heat shock protein 90 inhibitors, pan-HER2 tyrosine kinase inhibitors, antibody-drug conjugates, immunotherapy agents (antibodies and vaccines), radioimmunotherapy and HER2 specific affinity proteins. Possible developmental issues are the complexity of the molecular biology of the HER2 positive cancer cell, the occurrence of resistance, toxicity and the high cost. EXPERT OPINION: The determination of the right sequence of use of old and new therapies remains a challenging issue. The selection of patients who do or don't benefit from potentially toxic chemotherapy is also difficult. Central nervous system metastases are a common problem in HER2 positive breast cancer that needs to be addressed in future trials. PMID- 26817603 TI - Long- versus short-interval follow-up of cytologically benign thyroid nodules: a prospective cohort study. AB - BACKGROUND: Thyroid nodules are common, and most are benign. Given the risk of false-negative cytology (i.e. malignancy), follow-up is recommended after 1-2 years, though this recommendation is based solely on expert opinion. Sonographic appearance may assist with planning, but is limited by large inter-observer variability. We therefore compared the safety and efficacy of long- versus short interval follow-up after a benign initial aspiration, regardless of sonographic appearance. METHODS: This study evaluated all patients referred to the Brigham and Women's Hospital Thyroid Nodule Clinic, between 1999 and 2010, with a cytologically benign nodule >1 cm and who had returned for follow-up sonographic evaluation. Despite standard clinical recommendations, variation in patient compliance resulted in variable follow-up intervals from time of initial aspiration to the first repeat evaluation. Main outcome measures included nodule growth, repeat fine needle aspiration (FNA), thyroidectomy, malignancy, and disease-specific mortality. RESULTS: We evaluated 1,254 patients with 1,819 cytologically benign nodules, with a median time to first follow-up of 1.4 years (range, 0.5-14.1 years). The longer the follow-up interval, the more nodules grew and the more repeat FNAs were performed (P <0.001). The most clinical meaningful endpoints of malignancy or mortality, however, did not differ between the various follow-up intervals. The risk of a thyroidectomy (usually because of compressive symptoms) increased when time to first follow-up exceeded >3 years (4.9% vs. 1.2%, P = 0.0001), though no difference in malignancy risk was identified (0.2 0.8%, P = 0.77). No (0%) thyroid cancer-specific deaths were identified in either cohort. CONCLUSIONS: While expert opinion currently recommends repeat evaluation of a cytologically benign nodule at 1-2 years, these are the first data to demonstrate that this interval can be safely extended to 3 years without increased mortality or patient harm. Nodule growth can be expected, though detection of malignancies is unchanged. While replication of these data in large prospective multicenter studies is needed, this extension in follow-up interval would reduce unnecessary visits and medical interventions for millions of affected patients worldwide, leading to healthcare savings. Please see related commentary article: http://dx.doi.org/10.1186/s12916-016-0559-9 and research article: http://dx.doi.org/10.1186/s12916-015-0419-z . PMID- 26817604 TI - Safety and tolerability of azilsartan medoxomil in subjects with essential hypertension: a one-year, phase 3, open-label study. AB - This 56-week phase 3, open-label, treat-to-target study, involving 2 consecutive, non-randomized cohorts, evaluated the safety and tolerability of azilsartan medoxomil (AZL-M) in essential hypertension (mean baseline blood pressure [BP] 152/100 mmHg). All subjects (n = 669) initiated AZL-M 40 mg QD, force-titrated to 80 mg QD at week 4, if tolerated. From week 8, subjects could receive additional medications, starting with chlorthalidone (CLD) 25 mg QD (Cohort 1) or hydrochlorothiazide (HCTZ) 12.5-25 mg QD (Cohort 2), if required, to reach BP targets. Adverse events (AEs) were reported in 75.9% of subjects overall in the two cohorts (73.8% Cohort 1, 78.5% Cohort 2). The most common AEs were dizziness (14.3%), headache (9.9%) and fatigue (7.2%). Transient serum creatinine elevations were more frequent with add-on CLD. Clinic systolic/diastolic BP (observed cases at week 56) decreased by 25.2/18.4 mmHg (Cohort 1) and 24.2/17.9 mmHg (Cohort 2). These results demonstrate that AZL-M is well tolerated over the long term and provides stable BP improvements when used in a treat-to-target BP approach with thiazide-type diuretics. PMID- 26817605 TI - Prevalence and antimicrobial susceptibility profiles of Staphylococcus aureus nasal carriage among pre-clinical and clinical medical students in a Tanzanian University. AB - BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) nasal carriage is a potential niche for spread and a risk factor for subsequent infections. Despite the fact that medical students are exposed to patients in the hospital during their training, information on S. aureus and MRSA nasal carriage among medical students in Tanzania remains to be dearth so as to guide appropriate infection control and preventive measures. METHODS: A cross-sectional study involving 314 medical students, pre-clinical (n = 166) and clinical (n = 148), at Catholic University of Health and Allied Sciences (CUHAS) was conducted from February to June 2013. Nasal swabs from eligible students were taken and processed using standard operating procedures so as to identify S. aureus, MRSA and their respective antimicrobial susceptibility patterns. RESULTS: The median age (interquartile range) of the study participants was 24 (22-27) years with approximately 69.4% being males. S. aureus accounted for 21.0% (66/314) of which 1.5% (1/66) was MRSA; giving an overall MRSA nasal carriage prevalence of 0.3% (1/314). Staphylococcus aureus carriage among pre-clinical and clinical students were 19.9% (33/166) and 22.3% (33/148) respectively. MRSA carriage was found in one preclinical student with history of working in hospital for years prior to join CUHAS. Staphylococcus aureus carriage was significantly more in older median age group among clinical students compared to preclinical students (p < 0.001). Majority of the isolates were resistant to Ampicillin (87.9%, 58/66) while all were sensitive to Ciprofloxacin and Vancomycin. CONCLUSION: There is high prevalence of S. aureus carriage among medical students at CUHAS. Fortunately, MRSA was found in only one student. In the light of these findings, focused MRSA surveillance to other potential sources like health care workers, patients and environment should be carried out in this setting. PMID- 26817607 TI - RDDpred: a condition-specific RNA-editing prediction model from RNA-seq data. AB - BACKGROUND: RNA-editing is an important post-transcriptional RNA sequence modification performed by two catalytic enzymes, "ADAR"(A-to-I) and "APOBEC"(C-to U). By utilizing high-throughput sequencing technologies, the biological function of RNA-editing has been actively investigated. Currently, RNA-editing is considered to be a key regulator that controls various cellular functions, such as protein activity, alternative splicing pattern of mRNA, and substitution of miRNA targeting site. DARNED, a public RDD database, reported that there are more than 300-thousands RNA-editing sites detected in human genome(hg19). Moreover, multiple studies suggested that RNA-editing events occur in highly specific conditions. According to DARNED, 97.62 % of registered editing sites were detected in a single tissue or in a specific condition, which also supports that the RNA-editing events occur condition-specifically. Since RNA-seq can capture the whole landscape of transcriptome, RNA-seq is widely used for RDD prediction. However, significant amounts of false positives or artefacts can be generated when detecting RNA-editing from RNA-seq. Since it is difficult to perform experimental validation at the whole-transcriptome scale, there should be a powerful computational tool to distinguish true RNA-editing events from artefacts. RESULT: We developed RDDpred, a Random Forest RDD classifier. RDDpred reports potentially true RNA-editing events from RNA-seq data. RDDpred was tested with two publicly available RNA-editing datasets and successfully reproduced RDDs reported in the two studies (90 %, 95 %) while rejecting false-discoveries (NPV: 75 %, 84 %). CONCLUSION: RDDpred automatically compiles condition-specific training examples without experimental validations and then construct a RDD classifier. As far as we know, RDDpred is the very first machine-learning based automated pipeline for RDD prediction. We believe that RDDpred will be very useful and can contribute significantly to the study of condition-specific RNA editing. RDDpred is available at http://biohealth.snu.ac.kr/software/RDDpred . PMID- 26817606 TI - Effects of non-supervised low intensity aerobic excise training on the microvascular endothelial function of patients with type 1 diabetes: a non pharmacological interventional study. AB - BACKGROUND: The aim of the present study was to evaluate changes in microvascular density and reactivity in patients with type 1 diabetes (T1D) resulting from low intensity chronic exercise training. METHODS: This study included 22 (34 +/- 7 ears) consecutive outpatients with T1D and disease duration > 6 years. We used intravital video-microscopy to measure basal skin capillary density and capillary recruitment using post-occlusive reactive hyperemia (PORH) in the dorsum of the fingers. Endothelium-dependent and -independent vasodilation of the skin microcirculation was evaluated in the forearm with a laser Doppler flow monitoring (LDF) system in combination with acetylcholine and sodium nitroprusside iontophoresis, PORH and local thermal hyperemia. RESULTS: The basal mean capillary density (MCD) after exercise training was significantly higher than before exercise (134 +/- 25 vs. 119 +/- 19 capillaries/mm(2), respectively; P = 0.0013). MCD during PORH was also higher after exercise (140 +/- 26 vs. 121 +/- 24 capillaries/mm(2), respectively; P < 0.0001). Endothelium-dependent capillary recruitment during PORH was also significantly higher after exercise (140 +/- 26 vs. 134 +/- 25 capillaries/mm(2), respectively; P < 0.0012). There were no significant changes in skin microvascular reactivity after exercise as investigated using LDF. CONCLUSIONS: Our results showed that low intensity aerobic exercise, performed four times per week for 12 weeks by patients with T1D, induces significant increases in microvascular density and endothelial dependent capillary reactivity. TRIAL REGISTRATION: ClinicalTrials.gov NCT02441504. Registered 7 May 2015. PMID- 26817608 TI - H2AX phosphorylation and DNA damage kinase activity are dispensable for herpes simplex virus replication. AB - BACKGROUND: Herpes simplex virus type 1 (HSV-1) can establish both lytic and latent infections in humans. The phosphorylation of histone H2AX, a common marker of DNA damage, during lytic infection by HSV-1 is well established. However, the role(s) of H2AX phosphorylation in lytic infection remain unclear. METHODS: Following infection of human foreskin fibroblasts by HSV-1 or HSV-2, we assayed the phosphorylation of H2AX in the presence of inhibitors of transcription, translation, or viral DNA replication, or in the presence of inhibitors of ATM and ATR kinases (KU-55933 and VE-821, respectively). We also assayed viral replication in fibroblasts in the presence of the kinase inhibitors or siRNAs specific for ATM and ATR, as well as in cell lines deficient for either ATR or ATM. RESULTS: The expression of viral immediate-early and early proteins (including the viral DNA polymerase), but not viral DNA replication or late protein expression, were required for H2AX phosphorylation following HSV-1 infection. Inhibition of ATM kinase activity prevented HSV-stimulated H2AX phosphorylation but had only a minor effect on DNA replication and virus yield in HFF cells. These results differ from previous reports of a dramatic reduction in viral yield following chemical inhibition of ATM in oral keratinocytes or following infection of ATM(-/-) cells. Inhibition of the closely related kinase ATR (whether by chemical inhibitor or siRNA disruption) had no effect on H2AX phosphorylation and reduced viral DNA replication only moderately. During infection by HSV-2, H2AX phosphorylation was similarly dispensable but was dependent on both ATM activity and viral DNA replication. CONCLUSION: H2AX phosphorylation represents a cell type-specific and virus type-specific host response to HSV infection with little impact on viral infection. PMID- 26817610 TI - Eph-B4 mediates vein graft adaptation by regulation of endothelial nitric oxide synthase. AB - OBJECTIVE: Vein graft adaptation is characterized by loss of expression of the tyrosine kinase receptor Eph-B4, the embryonic determinant of venous identity, without increased expression of its ligand ephrin-B2, the embryonic determinant of arterial identity. Endothelial nitric oxide synthase (eNOS) is an important mediator of vessel remodeling. We hypothesized that the mechanism of action of Eph-B4 during vein graft adaptation might be through regulation of downstream eNOS activity. METHODS: Mouse lung endothelial cells were stimulated with ephrin B2/Fc, without and with preclustering, without and with the eNOS inhibitor Nomega nitro-l-arginine methyl ester hydrochloride or the Eph-B4 inhibitor NVP-BHG712, and assessed by Western blot and immunofluorescence for eNOS and Eph-B4 phosphorylation. Nitric oxide (NO) production was assessed using an NO-specific chemiluminescence analyzer. Cell migration was assessed using a Transwell assay. Human and mouse vein graft specimens were examined for eNOS activity by Western blot, and vessel remodeling was assessed in vein grafts in wild-type or eNOS knockout mice. RESULTS: Ephrin-B2/Fc stimulated both Eph-B4 and eNOS phosphorylation in a bimodal temporal distribution (n = 4; P < .05), with preclustered ephrin-B2/Fc causing prolonged peak Eph-B4 and eNOS phosphorylation as well as altered subcellular localization (n = 4; P < .05). Ephrin-B2/Fc increased NO release (n = 3; P < .01) as well as increased endothelial cell migration (n = 6; P < .05) in an eNOS-dependent fashion. Both human and mouse vein grafts showed increased eNOS phosphorylation compared with normal veins (n = 3; P < .05). Vein grafts from eNOS knockout mice showed less dilation and less wall thickening compared with wild-type vein grafts (n = 7; P < .05). CONCLUSIONS: eNOS is a mediator of vein graft adaptation to the arterial environment. Eph-B4 stimulates eNOS phosphorylation in vitro and may mediate vein graft adaptation by regulation of eNOS activity in vivo. PMID- 26817611 TI - Pharmacologic blockade and genetic deletion of androgen receptor attenuates aortic aneurysm formation. AB - BACKGROUND: Testosterone is theorized to play a major role in the pathophysiology of abdominal aortic aneurysms (AAAs) because this disease occurs primarily in men. The role of the androgen receptor (AR) in the formation of AAAs has not been well elucidated, and therefore, it is hypothesized that androgen blockade will attenuate experimental aortic aneurysm formation. METHODS: Aortas of 8- to 12 week-old male C57Bl/6 wild-type (WT) mice or male AR knockout (AR(-/-)) mice were perfused with purified porcine pancreatic elastase (0.35 U/mL) to induce AAA formation. Two groups of WT male mice were treated with the AR blockers flutamide (50 mg/kg) or ketoconazole (150 mg/kg) twice daily by intraperitoneal injection. Aortas were harvested on day 14 after video micrometry was used to measure AAA diameter. Cytokine arrays and histologic analysis were performed on aortic tissue. Groups were compared using an analysis of variance and a Tukey post hoc test. RESULTS: Flutamide and ketoconazole treatment (mean +/- standard error of the mean) attenuated AAA formation in WT mice (84.2% +/- 22.8% [P = .009] and 91.5% +/- 18.2% [P = .037]) compared with WT elastase (121% +/- 5.23%). In addition, AR(-/-) mice showed attenuation of AAA growth (64.4% +/- 22.7%; P < .0001) compared with WT elastase. Cytokine arrays of aortic tissue revealed decreased levels of proinflammatory cytokines interleukin (IL)-alpha, IL-6, and IL-17 in flutamide-treated and AR(-/-) groups compared with controls. CONCLUSIONS: Pharmacologic and genetic AR blockade cause attenuation of AAA formation. Therapies for AR blockade used in prostate cancer may provide medical treatment to halt progression of AAAs in humans. PMID- 26817612 TI - Standard off-the-shelf versus custom-made multibranched thoracoabdominal aortic stent grafts. AB - OBJECTIVE: The complex aortic branch anatomy in thoracoabdominal aortic aneurysms (TAAAs) and pararenal aortic aneurysms (PRAAs) presents a challenge for endovascular repair. The multibranched endovascular device has durable midterm results with use of a custom branch stent graft (CSG) configuration. The midterm results with use of the standard branch stent graft (SSG) configuration are unknown, but it has the advantage of off-the-shelf technology. The goal of this study was to compare the midterm outcomes of CSG and SSG multibranched endovascular devices. METHODS: From July 2005 to September 2014, 133 patients underwent elective endovascular repair of TAAA and PRAA in a prospective trial. Beginning in December 2008, SSGs were used in those with suitable anatomy. RESULTS: Fifty patients (mean age, 71 +/- 7 years; 11 women [22%]) were treated using SSGs, and 83 patients (mean age, 74 +/- 9 years; 22 women [26.5%]) underwent repair using CSGs. The SSG and CSG groups were similar with regard to aneurysm size, aneurysm extent, and medical comorbidities, with the sole exception of lung disease, which was more common in the SSG group. All stent grafts were deployed as intended, with no conversions to open repair. Mean +/- standard deviation follow-up (days) was 694 +/- 525 for the SSG group and 942 +/- 764 for the CSG group (P = .045). There were no significant differences in aneurysm-related death, renal failure requiring dialysis, stroke, endoleak, visceral or renal branch occlusion, lower extremity weakness, or reintervention (P > .05 for each). The volume of contrast material was significantly lower in those with SSGs compared with CSGs (P = .016), but there were no significant differences in operative or fluoroscopy times. Time to treatment (days from consent to surgery) was significantly lower in SSG patients compared with CSG patients (P = .01). CONCLUSIONS: For patients with suitable anatomy, the use of SSGs for TAAA and PRAA repair results in significantly shorter wait times to surgery and is as safe, effective, and durable in the midterm compared with CSGs. PMID- 26817614 TI - Evolution of Jahn-Teller distortion, transport and dielectric properties with doping in perovskite NdFe1-xMnxO3 (0 <= x <= 1) compounds. AB - We have carried out dielectric and transport measurements in NdFe1-xMnxO3 (0 <= x <= 1) series of compounds and studied the variation of activation energy due to a change in Mn concentration. Despite similar ionic radii in Mn(3+) and Fe(3+), large variation is observed in the lattice parameters and a crossover from dynamic to static Jahn-Teller distortion is discernible. The Fe/Mn-O-Fe/Mn bond angle on the ab plane shows an anomalous change with doping. With an increase in the Mn content, the bond angle decreases until x = 0.6; beyond this, it starts rising until x = 0.8 and again falls after that. A similar trend is observed in activation energies estimated from both transport and dielectric relaxation by assuming a small polaron hopping (SPH) model. Impedance spectroscopy measurements delineate grain and grain boundary contributions separately both of which follow the SPH model. Frequency variation of the dielectric constant is in agreement with the modified Debye law from which relaxation dispersion is estimated. PMID- 26817615 TI - Decreased Expression of Caveolin-1 and E-Cadherin Correlates with the Clinicopathologic Features of Gastric Cancer and the EMT Process. AB - BACKGROUND: Recent researches and relevant patents have been reported to prove the significant value of Caveolin-1 (Cav-1) in cancer diagnosis and treatment. OBJECTIVE: Our study aimed to study the role of Cav-1 in gastric cancer progression and investigate the relationship between Cav-1/E-cadherin expression and the clinical status of gastric cancer. METHOD: Immunohistochemistry was applied to detect the expression of Cav-1 and E-cadherin in gastric cancer in a tissue microarray. Real-time PCR was used to further detect the mRNA expression of Cav-1 and E-cadherin in tumor-derived and peritumoral tissues and in different gastric cancer cell lines. The expression of E-cadherin was analyzed by Western Blot and the cell migration ability was examined by Transwell migration assays after downregulation of Cav-1 using siRNA. RESULTS: The staining of Cav-1 and E cadherin were both strong in all 5 of the normal gastric tissues, while in gastric cancer tissues the staining of Cav-1 and E-cadherin were downregulated (44&33 negative, 21&22weak and 5&15 strong). And their level was correlated with tumor clinical stage, pathological grade, and metastasis status. Moreover, there was a positive correlation between Cav-1 expression and E-cadherin expression in gastric cancer tissues(r = 0.42, P < 0.05). Knockdown of Cav-1 resulted in decreased expression of E-cadherin, cell morphology changes and elevated migration ability of gastric cancer cells. CONCLUSION: Decreased expression of Cav-1 and E-cadherin may play an important role in the progression of gastric cancer; Knockdown of Cav-1 may promote EMT of gastric cancer by targeting E cadherin. PMID- 26817613 TI - Proteomic approaches to uncovering virus-host protein interactions during the progression of viral infection. AB - The integration of proteomic methods to virology has facilitated a significant breadth of biological insight into mechanisms of virus replication, antiviral host responses and viral subversion of host defenses. Throughout the course of infection, these cellular mechanisms rely heavily on the formation of temporally and spatially regulated virus-host protein-protein interactions. Reviewed here are proteomic-based approaches that have been used to characterize this dynamic virus-host interplay. Specifically discussed are the contribution of integrative mass spectrometry, antibody-based affinity purification of protein complexes, cross-linking and protein array techniques for elucidating complex networks of virus-host protein associations during infection with a diverse range of RNA and DNA viruses. The benefits and limitations of applying proteomic methods to virology are explored, and the contribution of these approaches to important biological discoveries and to inspiring new tractable avenues for the design of antiviral therapeutics is highlighted. PMID- 26817617 TI - First record of the genus Jenynsia from marine water on the coast of Punta del Este, Maldonado, Uruguay (Cyprinodontiformes: Anablepidae). AB - The first report of the genus Jenynsia occurring in marine waters is presented here. The evolution of high salinity tolerance within Anablepidae is discussed and a hypothesis is proposed that this characteristic is a plesiomorphic trait in Jenynsia which was probably present in the common ancestor of the Anablepidae. PMID- 26817616 TI - The FTF gene family regulates virulence and expression of SIX effectors in Fusarium oxysporum. AB - The FTF (Fusarium transcription factor) gene family comprises a single copy gene, FTF2, which is present in all the filamentous ascomycetes analysed, and several copies of a close relative, FTF1, which is exclusive to Fusarium oxysporum. An RNA-mediated gene silencing system was developed to target mRNA produced by all the FTF genes, and tested in two formae speciales: F. oxysporum f. sp. phaseoli (whose host is common bean) and F. oxysporum f. sp. lycopersici (whose host is tomato). Quantification of the mRNA levels showed knockdown of FTF1 and FTF2 in randomly isolated transformants of both formae speciales. The attenuation of FTF expression resulted in a marked reduction in virulence, a reduced expression of several SIX (Secreted In Xylem) genes, the best studied family of effectors in F. oxysporum, and lower levels of SGE1 (Six Gene Expression 1) mRNA, the presumptive regulator of SIX expression. Moreover, the knockdown mutants showed a pattern of colonization of the host plant similar to that displayed by strains devoid of FTF1 copies (weakly virulent strains). Gene knockout of FTF2 also resulted in a reduction in virulence, but to a lesser extent. These results demonstrate the role of the FTF gene expansion, mostly the FTF1 paralogues, as a regulator of virulence in F. oxysporum and suggest that the control of effector expression is the mechanism involved. PMID- 26817618 TI - Intracrine Androgens Enhance Decidualization and Modulate Expression of Human Endometrial Receptivity Genes. AB - The endometrium is a complex, steroid-dependent tissue that undergoes dynamic cyclical remodelling. Transformation of stromal fibroblasts (ESC) into specialised secretory cells (decidualization) is fundamental to the establishment of a receptive endometrial microenvironment which can support and maintain pregnancy. Androgen receptors (AR) are present in ESC; in other tissues local metabolism of ovarian and adrenal-derived androgens regulate AR-dependent gene expression. We hypothesised that altered expression/activity of androgen biosynthetic enzymes would regulate tissue availability of bioactive androgens and the process of decidualization. Primary human ESC were treated in vitro for 1 8 days with progesterone and cAMP (decidualized) in the presence or absence of the AR antagonist flutamide. Time and treatment-dependent changes in genes essential for a) intra-tissue biosynthesis of androgens (5alpha-reductase/SRD5A1, aldo-keto reductase family 1 member C3/AKR1C3), b) establishment of endometrial decidualization (IGFBP1, prolactin) and c) endometrial receptivity (SPP1, MAOA, EDNRB) were measured. Decidualization of ESC resulted in significant time dependent changes in expression of AKR1C3 and SRD5A1 and secretion of T/DHT. Addition of flutamide significantly reduced secretion of IGFBP1 and prolactin and altered the expression of endometrial receptivity markers. Intracrine biosynthesis of endometrial androgens during decidualization may play a key role in endometrial receptivity and offer a novel target for fertility treatment. PMID- 26817619 TI - Evidence and implications of direct charge excitation as the dominant mechanism in plasmon-mediated photocatalysis. AB - Plasmonic metal nanoparticles enhance chemical reactions on their surface when illuminated with light of particular frequencies. It has been shown that these processes are driven by excitation of localized surface plasmon resonance (LSPR). The interaction of LSPR with adsorbate orbitals can lead to the injection of energized charge carriers into the adsorbate, which can result in chemical transformations. The mechanism of the charge injection process (and role of LSPR) is not well understood. Here we shed light on the specifics of this mechanism by coupling optical characterization methods, mainly wavelength-dependent Stokes and anti-Stokes SERS, with kinetic analysis of photocatalytic reactions in an Ag nanocube-methylene blue plasmonic system. We propose that localized LSPR-induced electric fields result in a direct charge transfer within the molecule-adsorbate system. These observations provide a foundation for the development of plasmonic catalysts that can selectively activate targeted chemical bonds, since the mechanism allows for tuning plasmonic nanomaterials in such a way that illumination can selectively enhance desired chemical pathways. PMID- 26817620 TI - Amplification and generation of ultra-intense twisted laser pulses via stimulated Raman scattering. AB - Twisted Laguerre-Gaussian lasers, with orbital angular momentum and characterized by doughnut-shaped intensity profiles, provide a transformative set of tools and research directions in a growing range of fields and applications, from super resolution microcopy and ultra-fast optical communications to quantum computing and astrophysics. The impact of twisted light is widening as recent numerical calculations provided solutions to long-standing challenges in plasma-based acceleration by allowing for high-gradient positron acceleration. The production of ultra-high-intensity twisted laser pulses could then also have a broad influence on relativistic laser-matter interactions. Here we show theoretically and with ab initio three-dimensional particle-in-cell simulations that stimulated Raman backscattering can generate and amplify twisted lasers to petawatt intensities in plasmas. This work may open new research directions in nonlinear optics and high-energy-density science, compact plasma-based accelerators and light sources. PMID- 26817621 TI - A randomized factorial trial of disulfiram and contingency management to enhance cognitive behavioral therapy for cocaine dependence. AB - BACKGROUND: This study evaluated the extent to which the addition of disulfiram and contingency management for adherence and abstinence (CM), alone and in combination, might enhance the effects of cognitive behavioral therapy (CBT) for cocaine use disorders. METHODS: Factorial randomized double blind (for medication condition) clinical trial where CBT served as the platform and was delivered in weekly individual sessions in a community-based outpatient clinic. 99 outpatients who met DSM-IV criteria for current cocaine dependence were assigned to receive either disulfiram or placebo, and either CM or no CM. Cocaine and other substance use was assessed via a daily calendar with thrice weekly urine sample testing for 12 weeks with a one-year follow-up (80% interviewed at one year). RESULTS: The primary hypothesis that CM and disulfiram would produce the best cocaine outcomes was not confirmed, nor was there a main effect for disulfiram. For the primary outcome (percent days of abstinence, self report), there was a significant interaction, with the best cocaine outcomes were seen for the combination of CM and placebo, with the two groups assigned to disulfiram associated with intermediate outcomes, and poorest cocaine outcome among those assigned to placebo and no CM. The secondary outcome (urinalysis) indicated a significant effect favoring CM over no CM but the interaction effect was not significant. One year follow-up data indicated sustained treatment effects across conditions. CONCLUSIONS: CM enhances outcomes for CBT treatment of cocaine dependence, but disulfiram provided no added benefit to the combination of CM and CBT. PMID- 26817622 TI - An Injectable Enzymatically Crosslinked Carboxymethylated Pullulan/Chondroitin Sulfate Hydrogel for Cartilage Tissue Engineering. AB - In this study, an enzymatically cross-linked injectable and biodegradable hydrogel system comprising carboxymethyl pullulan-tyramine (CMP-TA) and chondroitin sulfate-tyramine (CS-TA) conjugates was successfully developed under physiological conditions in the presence of both horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) for cartilage tissue engineering (CTTE). The HRP crosslinking method makes this injectable system feasible, minimally invasive and easily translatable for regenerative medicine applications. The physicochemical properties of the mechanically stable hydrogel system can be modulated by varying the weight ratio and concentration of polymer as well as the concentrations of crosslinking reagents. Additionally, the cellular behaviour of porcine auricular chondrocytes encapsulated into CMP-TA/CS-TA hydrogels demonstrates that the hydrogel system has a good cyto-compatibility. Specifically, compared to the CMP TA hydrogel, these CMP-TA/CS-TA composite hydrogels have enhanced cell proliferation and increased cartilaginous ECM deposition, which significantly facilitate chondrogenesis. Furthermore, histological analysis indicates that the hydrogel system exhibits acceptable tissue compatibility by using a mouse subcutaneous implantation model. Overall, the novel injectable pullulan/chondroitin sulfate composite hydrogels presented here are expected to be useful biomaterial scaffold for regenerating cartilage tissue. PMID- 26817624 TI - The Important Role for Intravenous Iron in Perioperative Patient Blood Management in Major Abdominal Surgery: A Randomized Controlled Trial. AB - OBJECTIVE: To determine if preoperative intravenous (IV) iron improves outcomes in abdominal surgery patients. SUMMARY BACKGROUND DATA: Preoperative iron deficiency anemia (IDA) occurs frequently; however if left untreated, increases the risk of blood transfusion allogeneic blood transfusion (ABT). Limited evidence supports IDA treatment with preoperative IV iron. This randomized controlled trial aimed to determine whether perioperative IV iron reduced the need for ABT. METHODS: Between August 2011 and November 2014, 72 patients with IDA were assigned to receive either IV iron or usual care. The primary endpoint was incidence of ABT. Secondary endpoints were various hemoglobin (Hb) levels, change in Hb between time points, length of stay, iron status, morbidity, mortality, and quality of life 4 weeks postsurgery. RESULTS: A 60% reduction in ABT was observed in the IV iron group compared with the usual care group (31.25% vs 12.5%). Hb values, although similar at randomization, improved by 0.8 g/dL with IV iron compared with 0.1 g/dL with usual care (P = 0.01) by the day of admission. The IV iron group had higher Hb 4 weeks after discharge compared with the usual care group (1.9 vs 0.9 g/dL, P = 0.01), and a shorter length of stay (7.0 vs 9.7 d, P = 0.026). There was no difference in discharge Hb levels, morbidity, mortality, or quality of life. CONCLUSIONS: Administration of perioperative IV iron reduces the need for blood transfusion, and is associated with a shorter hospital stay, enhanced restoration of iron stores, and a higher mean Hb concentration 4 weeks after surgery. PMID- 26817625 TI - Near Infrared Phosphorescent, Non-oxidizable Palladium and Platinum Perfluoro phthalocyanines. AB - New Pd(II) and Pt(II) complexes with a highly electron-deficient ligand (H2 PcF64 ) were conveniently prepared in a three-step synthesis. This is the first time that the phosphorescence of phthalocyanines with a H2 PcF64 framework has been measured. Based on these measurements, the triplet-state energies (ET ) were directly determined. Transient absorption experiments revealed broad T1 ->Tn absorption spanning from ca. 350 to ca. 1000 nm and allowed determination of the triplet-state lifetimes. Removal of the Pd or Pt from the perfluoro phthalocyanine resulted in a significant increase of the triplet lifetime for H2 PcF64 . The very efficient intersystem crossing observed for both PdPcF64 and PtPcF64 leads to residual fluorescence and suppresses the fluorescence lifetimes to less than 50 ps. The absence of Pd and Pt in the perfluoro-phthalocyanine ligand, viz. H2 PcF64 , led to a recovery of fluorescence. Cyclic voltamperometry studies pointed to complete resistance of PdPcF64 and PtPcF64 to oxidation and very strong electron affinity, which rendered these materials very good electron acceptors (n-type materials). The presence of d-orbital metals such as Pd(II) and Pt(II) in the phthalocyanine ring stabilizes their reduced forms, as indicated by the spectroelectrochemical experiments. PdPcF64 and PtPcF64 easily sensitize singlet oxygen production with very high quantum yields. Both phthalocyanines presented resistance to photodegradation in the solid state under aerobic conditions and under intense irradiation. PMID- 26817626 TI - Mycobacterium tuberculosis RuvX is a Holliday junction resolvase formed by dimerisation of the monomeric YqgF nuclease domain. AB - The Mycobacterium tuberculosis genome possesses homologues of the ruvC and yqgF genes that encode putative Holliday junction (HJ) resolvases. However, their gene expression profiles and enzymatic properties have not been experimentally defined. Here we report that expression of ruvC and yqgF is induced in response to DNA damage. Protein-DNA interaction assays with purified M. tuberculosis RuvC (MtRuvC) and YqgF (MtRuvX) revealed that both associate preferentially with HJ DNA, albeit with differing affinities. Although both MtRuvC and MtRuvX cleaved HJ DNA in vitro, the latter displayed robust HJ resolution activity by symmetrically related, paired incisions. MtRuvX showed a higher binding affinity for the HJ structure over other branched recombination and replication intermediates. An MtRuvX(D28N) mutation, eliminating one of the highly conserved catalytic residues in this class of endonucleases, dramatically reduced its ability to cleave HJ DNA. Furthermore, a unique cysteine (C38) fulfils a crucial role in HJ cleavage, consistent with disulfide-bond mediated dimerization being essential for MtRuvX activity. In contrast, E. coli YqgF is monomeric and exhibits no branched DNA binding or cleavage activity. These results fit with a functional modification of YqgF in M. tuberculosis so that it can act as a dimeric HJ resolvase analogous to that of RuvC. PMID- 26817627 TI - Spatial proximity statistics suggest a regulatory role of protein phosphorylation on compound binding. AB - Phosphorylation is an important post-translational modification that regulates protein function by the attachment of negatively charged phosphate groups to phosphorylatable amino acid residues. As a mode of action, an influence of phosphorylation on the binding of compounds to proteins has been discussed and described for a number of proteins in the literature. However, a systematic statistical survey probing for enriched phosphorylation sites close to compound binding sites in support of this notion and with properly chosen random reference distributions has not been presented yet. Using high-resolution protein structures from the Protein Data Bank including their co-crystallized non covalently bound compounds and experimentally determined phosphorylation sites, we analyzed the pairwise distance distributions of phosphorylation and compound binding sites on protein surfaces. We found that phosphorylation sites are indeed located at significantly closer distances to compounds than expected by chance holding true specifically also for the subset of compound binding sites serving as catalytic sites of metabolic reactions. This tendency was particularly evident when treating phosphorylation sites as collective sets supporting the relevance of phosphorylation hotspots. Interestingly, phosphorylation sites were found to be closer to negatively charged than to positively charged compounds suggesting a stronger modulation of the binding of negatively charged compounds in dependence on phosphorylation status than on positively charged compounds. The enrichment of phosphorylation sites near compound binding sites confirms a regulatory role of phosphorylation in compound binding and provides a solid statistical basis for the literature-reported selected events. PMID- 26817628 TI - Effect of telemonitoring of cardiac implantable electronic devices on healthcare utilization: a meta-analysis of randomized controlled trials in patients with heart failure. AB - AIMS: Implantable device telemonitoring (DTM) is a diagnostic adjunct to traditional face-to-face hospital visits. Remote device follow-up and earlier diagnoses facilitated by DTM should reduce healthcare utilization. We explored whether DTM reduces healthcare utilization over standard of care (SoC), without compromising patient outcomes. METHODS AND RESULTS: This systematic review and meta-analysis of 11 randomized controlled trials on DTM in patients with heart failure consisted of 5702 patients, with a median of 117 [interquartile range (IQR) 76-331] patients per study [age 65 years (IQR 63-67)] and follow-up range of 12-36 months. DTM was associated with a reduction in total number of visits [planned, unplanned, and emergency room (ER)] [relative risk (RR) 0.56; 95% confidence interval (CI) 0.43-0.73, P < 0.001]. Rates of cardiac hospitalizations (RR 0.96; 95% CI 0.82-1.12, P = 0.60) and the composite endpoints of ER, unplanned hospital visits, or hospitalizations (RR 0.99; 95% CI 0.68-1.43, P = 0.96) was similar between the DTM and the SoC groups. An increase in the total number of ER or unscheduled visits (RR 1.37; 95% CI 1.11-1.70, P = 0.004) was observed. This effect was consistent and statistically significant for all studies. Total and cardiac mortality were similar between the groups (DTM RR 0.90; 95% CI 0.69-1.16, P = 0.41; and DTM RR 0.93; 95% CI 0.51-1.69, P = 0.80). Monetary costs favoured DTM (10-55% reduction in five studies). CONCLUSIONS: Compared with SoC, DTM is associated with a marked reduction in planned hospital visits. In addition, DTM was associated with lower monetary costs, despite a modest increase in unplanned hospital and ER visits. DTM did not compromise survival. PMID- 26817629 TI - Vitamin D mitigates the adverse effects of obesity on breast cancer in mice. AB - Obesity is an established risk factor for postmenopausal breast cancer (BCa), insulin resistance, and vitamin D deficiency, and all contribute to increased synthesis of mammary estrogens, the drivers of estrogen receptor-positive (ER+) BCa growth. As both dietary vitamin D and calcitriol treatments inhibit breast estrogen synthesis and signaling, we hypothesized that vitamin D would be especially beneficial in mitigating the adverse effects of obesity on ER+BCa. To assess whether obesity exerted adverse effects on BCa growth and whether vitamin D compounds could reduce these unfavorable effects, we employed a diet-induced obesity (DIO) model in ovariectomized C57BL/6 mice. Breast tumor cells originally from syngeneic Mmtv-Wnt1 transgenic mice were then implanted into the mammary fat pads of lean and obese mice. DIO accelerated the initiation and progression of the mammary tumors. Treatments with either calcitriol or dietary vitamin D reduced the adverse effects of obesity causing a delay in tumor appearance and inhibiting continued tumor growth. Beneficial actions of treatments with vitamin D or calcitriol on BCa and surrounding adipose tissue included repressed Esr1, aromatase, and Cox2 expression; decreased tumor-derived estrogen and PGE2; reduced expression of leptin receptors; and increased adiponectin receptors. We demonstrate that vitamin D treatments decreased insulin resistance, reduced leptin, and increased adiponectin signaling and also regulated the LKB1/AMPK pathway contributing to an overall decrease in local estrogen synthesis in the obese mice. We conclude that calcitriol and dietary vitamin D, acting by multiple interrelated pathways, mitigate obesity-enhanced BCa growth in a postmenopausal setting. PMID- 26817631 TI - Older Adults With Three Generations of Kin: Prevalence, Correlates, and Transfers. AB - Objectives: We document the prevalence and sociodemographic correlates of older adults with three generations of living kin and examine the patterns of transfers among this group compared with those with fewer generations of kin available. Method: We use the Health and Retirement Study (1998-2010) to estimate kin availability and intergenerational transfers among respondents in their 50s, 60s, and 70s. Results: It is far more common for older adults to have aging parents, children, and grandchildren than to have just two generations of kin (parents and children). Forty percent of adults in their 50s, 30% of those in their 60s, and 7.5% of those in their 70s have three generations of kin available. Hispanics and the least educated are more likely to have this generational configuration. The vast majority provides financial or in-kind transfers to at least one generation, and a large minority provides support to both older and younger generations. Discussion: Although there has been much concern about the strains among those sandwiched between parents and children, it is far more common among older adults to also have grandchildren, and many of these adults are transferring resources both upward and downward to multiple generations. PMID- 26817632 TI - Effects of RAAS Blockers on Atrial Fibrillation Prophylaxis: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: Impact of atrial fibrillation on clinical outcomes is well recognized, and application of renin-angiotensin-aldosterone system (RAAS) blockers for the prevention of atrial fibrillation (AF) is a theoretically appealing concept. However, clinical trials have yielded inconsistent results. METHODS: A pooled study of 26 randomized controlled trials (RCTs) assessing the efficacy of RAAS blockers on AF prophylaxis was performed. RESULTS: A total of 28 reports from 26 randomized controlled trials enrolled 165 387 patients, with an overall 24% reduction in the incidence of AF (odds ratio [OR]: 0.76, 95% confidence interval [CI]: 0.68-0.85], P = .000). Forty-nine percent reduction in the incidence of AF (OR: 0.51, 95% CI: 0.30-0.85, P = .010) in systolic heart failure was observed, whereas no significant effect was observed in patients with diastolic heart failure, postmyocardial infarction, and high cardiovascular disease risk. There was a 19% (OR: 0.81, 95% CI: 0.67-1.00, P = .037) reduction in new-onset and 54% (OR: 0.46, 95% CI: 0.33-0.62, P = .000) reduction in recurrent AF in hypertensive patients with 39% (OR: 0.61, 95% CI: 0.44-0.84, P = .003) risk reduction against calcium blockers and 41% (OR: 0.59, 95% CI: 0.44 0.80, P = .001) risk reduction against beta blockers. Angiotensin-receptor blocker appeared marginally superior to angiotensin-converting enzyme inhibitor in primary and secondary prevention. CONCLUSION: This study suggests that RAAS blockade effectively suppresses AF in systolic heart failure, and hypertensives derive greater benefit against new-onset and recurrent AF compared to beta blockers, calcium channel blockers, and diuretics. PMID- 26817630 TI - Decolonization in Prevention of Health Care-Associated Infections. AB - Colonization with health care-associated pathogens such as Staphylococcus aureus, enterococci, Gram-negative organisms, and Clostridium difficile is associated with increased risk of infection. Decolonization is an evidence-based intervention that can be used to prevent health care-associated infections (HAIs). This review evaluates agents used for nasal topical decolonization, topical (e.g., skin) decolonization, oral decolonization, and selective digestive or oropharyngeal decontamination. Although the majority of studies performed to date have focused on S. aureus decolonization, there is increasing interest in how to apply decolonization strategies to reduce infections due to Gram-negative organisms, especially those that are multidrug resistant. Nasal topical decolonization agents reviewed include mupirocin, bacitracin, retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, photodynamic therapy, omiganan pentahydrochloride, and lysostaphin. Mupirocin is still the gold standard agent for S. aureus nasal decolonization, but there is concern about mupirocin resistance, and alternative agents are needed. Of the other nasal decolonization agents, large clinical trials are still needed to evaluate the effectiveness of retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, omiganan pentahydrochloride, and lysostaphin. Given inferior outcomes and increased risk of allergic dermatitis, the use of bacitracin containing compounds cannot be recommended as a decolonization strategy. Topical decolonization agents reviewed included chlorhexidine gluconate (CHG), hexachlorophane, povidone-iodine, triclosan, and sodium hypochlorite. Of these, CHG is the skin decolonization agent that has the strongest evidence base, and sodium hypochlorite can also be recommended. CHG is associated with prevention of infections due to Gram-positive and Gram-negative organisms as well as Candida. Conversely, triclosan use is discouraged, and topical decolonization with hexachlorophane and povidone-iodine cannot be recommended at this time. There is also evidence to support use of selective digestive decontamination and selective oropharyngeal decontamination, but additional studies are needed to assess resistance to these agents, especially selection for resistance among Gram negative organisms. The strongest evidence for decolonization is for use among surgical patients as a strategy to prevent surgical site infections. PMID- 26817633 TI - Impact of point-of-care diagnostics on maternal outcomes in HIV-infected women: systematic review and meta-analysis protocol. AB - INTRODUCTION: Studies indicate substandard diagnostic care, delayed and missed diagnosis as some of the contributing factors to maternal mortality. The clinical impact of point-of-care (POC) diagnostics has been shown in the monitoring and treatment of a variety of infectious diseases, including HIV/AIDS and tuberculosis. The objective of this systematic review is to investigate the impact of POC diagnostics on maternal outcomes for HIV-infected women. METHODS: We will conduct a systematic review to evaluate the impact of POC diagnostics for improving desired healthcare outcomes for HIV-infected women. The search strategy will involve electronic databases including: Cochrane Infectious Disease Group Specialised Register; Cochrane Central Register of Control Trials, published in The Cochrane Library; PubMed; EBSCOhost and LILACS. The studies will be mapped in 2 stages: stage 1 will map studies descriptively by focus and method; stage 2 will involve additional inclusion criteria, quality assessment and data extraction undertaken by 2 reviewers in parallel. Evidence will be synthesised using relevant systematic research tools: meta-analysis and subgroup analysis will be conducted using RevMan and Stata 13 will be used for meta-regressions. We will follow recommendations described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Cochrane Handbook for Intervention Reviews. ETHICS AND DISSEMINATION: We anticipate finding a large number of studies on POC diagnostic interventions on maternal outcomes in HIV infected women, which, once summarised, will be useful to guide future diagnostic interventions. The protocol for the systematic review has been registered in PROSPERO. The study will be disseminated electronically and in print. It will also be presented to conferences related to HIV/AIDS, POC diagnostics and maternal health. TRIAL REGISTRATION NUMBER: PROSPERO CRD42014015439. PMID- 26817634 TI - Can HIV reverse transcriptase activity assay be a low-cost alternative for viral load monitoring in resource-limited settings? AB - OBJECTIVE: To evaluate the performance and cost of an HIV reverse transcriptase enzyme activity (HIV-RT) assay in comparison to an HIV-1 RNA assay for routine viral load monitoring in resource limited settings. DESIGN: A cohort-based longitudinal study. SETTING: Two antiretroviral therapy (ART) centres in Karnataka state, South India, providing treatment under the Indian AIDS control programme. PARTICIPANTS: A cohort of 327 HIV-1-infected Indian adult patients initiating first-line ART. OUTCOME MEASURES: Performance and cost of an HIV-RT assay (ExaVir Load V3) in comparison to a gold standard HIV-1 RNA assay (Abbott m2000rt) in a cohort of 327 Indian patients before (WK00) and 4 weeks (WK04) after initiation of first-line therapy. RESULTS: Plasma viral load was determined by an HIV-1 RNA assay and an HIV-RT assay in 629 samples (302 paired samples and 25 single time point samples at WK00) obtained from 327 patients. Overall, a strong correlation of r=0.96 was observed, with good correlation at WK00 (r=0.84) and at WK04 (r=0.77). Bland-Altman analysis of all samples showed a good level of agreement with a mean difference (bias) of 0.22 log10copies/mL. The performance of ExaVir Load V3 was not negatively affected by a nevirapine/efavirenz based antiretroviral regimen. The per test cost of measuring plasma viral load by the Abbott m2000rt and ExaVir Load V3 assays in a basic lab setting was $36.4 and $16.8, respectively. CONCLUSIONS: The strong correlation between the HIV-RT and HIV-1 RNA assays suggests that the HIV-RT assay can be an affordable alternative option for monitoring patients on antiretroviral therapy in resource-limited settings. TRIAL REGISTRATION NUMBER: ISRCTN79261738. PMID- 26817635 TI - Improving accuracy and usability of growth charts: case study in Rwanda. AB - OBJECTIVES: We evaluate and compare manually collected paper records against electronic records for monitoring the weights of children under the age of 5. SETTING: Data were collected by 24 community health workers (CHWs) in 2 Rwandan communities, 1 urban and 1 rural. PARTICIPANTS: The same CHWs collected paper and electronic records. Paper data contain weight and age for 320 boys and 380 girls. Electronic data contain weight and age for 922 girls and 886 boys. Electronic data were collected over 9 months; most of the data is cross-sectional, with about 330 children with time-series data. Both data sets are compared with the international standard provided by the WHO growth chart. PRIMARY AND SECONDARY OUTCOME MEASURES: The plan was to collect 2000 individual records for the electronic data set--we finally collected 1878 records. Paper data were collected by the same CHWs, but most data were fragmented and hard to read. We transcribed data only from children for whom we were able to obtain the date of birth, to determine the exact age at the time of measurement. RESULTS: Mean absolute error (MAE) and mean absolute percentage error (MAPE) provide a way to quantify the magnitude of the error in using a given model. Comparing a model, log(weight)=a+b log(age), shows that electronic records provide considerable improvements over paper records, with 40% reduction in both performance metrics. Electronic data improve performance over the WHO model by 10% in MAPE and 7% in MAE. Results are statistically significant using the Kolmogorov-Smirnov test at p<0.01. CONCLUSIONS: This study demonstrates that using modern electronic tools for health data collection is allowing better tracking of health indicators. We have demonstrated that electronic records facilitate development of a country-specific model that is more accurate than the international standard provided by the WHO growth chart. PMID- 26817636 TI - Target prices for mass production of tyrosine kinase inhibitors for global cancer treatment. AB - OBJECTIVE: To calculate sustainable generic prices for 4 tyrosine kinase inhibitors (TKIs). BACKGROUND: TKIs have proven survival benefits in the treatment of several cancers, including chronic myeloid leukaemia, breast, liver, renal and lung cancer. However, current high prices are a barrier to treatment. Mass production of low-cost generic antiretrovirals has led to over 13 million people being on HIV/AIDS treatment worldwide. This analysis estimates target prices for generic TKIs, assuming similar methods of mass production. METHODS: Four TKIs with patent expiry dates in the next 5 years were selected for analysis: imatinib, erlotinib, lapatinib and sorafenib. Chemistry, dosing, published data on per-kilogram pricing for commercial transactions of active pharmaceutical ingredient (API), and quotes from manufacturers were used to estimate costs of production. Analysis included costs of excipients, formulation, packaging, shipping and a 50% profit margin. Target prices were compared with current prices. Global numbers of patients eligible for treatment with each TKI were estimated. RESULTS: API costs per kg were $347-$746 for imatinib, $2470 for erlotinib, $4671 for lapatinib, and $3000 for sorafenib. Basing on annual dose requirements, costs of formulation/packaging and a 50% profit margin, target generic prices per person-year were $128-$216 for imatinib, $240 for erlotinib, $1450 for sorafenib, and $4020 for lapatinib. Over 1 million people would be newly eligible to start treatment with these TKIs annually. CONCLUSIONS: Mass generic production of several TKIs could achieve treatment prices in the range of $128-$4020 per person-year, versus current US prices of $75161-$139,138. Generic TKIs could allow significant savings and scaling-up of treatment globally, for over 1 million eligible patients. PMID- 26817637 TI - Independent predictors of major adverse cardiovascular events in emergency department patients who are hospitalised with a suspected infection: a retrospective cohort study. AB - OBJECTIVE: Emergency department (ED) patients hospitalised with a suspected infection have an increased risk for major adverse cardiovascular events (MACE). This study aims to identify independent predictors of MACE after hospital admission which could be used for identification of high-risk patients who may benefit from preventive strategies. SETTING: Dutch tertiary care centre and urban hospital. PARTICIPANTS: Consecutive, hospitalised, ED patients with a suspected infection. DESIGN: This was a secondary analysis using an existing database in which consecutive, hospitalised, ED patients with a suspected infection were prospectively enrolled. Potential independent predictors, including illness severity, as assessed by the Predisposition, Infection, Response, Organ failure (PIRO) score, and classic cardiac risk factors were analysed by multivariable binary logistic regression. Prognostic and discriminative performance of the model was quantified by the Hosmer-Lemeshow test and receiver operator characteristics with area under the curve (AUC) analyses, respectively. Maximum sensitivity and specificity for identification of MACE were calculated. PRIMARY OUTCOME: MACE within 90 days after hospital admission. RESULTS: 36 (2.1%) of the 1728 included patients developed MACE <90 days after ED presentation. Independent predictors of MACE were the RO components of the PIRO score, reflecting acute organ failure, with a corrected OR (OR (95% CI) 1.1 (1.0 to 1.3) per point increase), presence of atrial fibrillation/flutter; OR 3.9 (2.0 to 7.7) and >2 classic cardiovascular risk factors; 2.2 (1.1 to 4.3). The AUC was 0.773, and the goodness-of-fit test had a p value of 0.714. These predictors identified MACE with 75% sensitivity and 70% specificity. CONCLUSIONS: Besides the classical cardiovascular risk factors, atrial fibrillation and signs of acute organ failure were independent risk factors of MACE in ED patients hospitalised with a suspected infection. Future studies should investigate whether preventive measures like antiplatelet therapy should be initialised in hospitalised ED patients with suspected infection and high risk for MACE. PMID- 26817638 TI - Psychological interventions to improve psychological well-being in people with dementia or mild cognitive impairment: systematic review and meta-analysis protocol. AB - INTRODUCTION: Dementia and mild cognitive impairment are associated with an increased risk of depression, anxiety, psychological distress and poor mental health-related quality of life. However, there is a lack of research examining the evidence base for psychological interventions targeting general psychological well-being within this population. Furthermore, there is little research relating to the design of randomised controlled trials examining psychological interventions for dementia and mild cognitive impairment, such as effective recruitment techniques, trial eligibility and appropriate comparators. METHODS AND ANALYSIS: Systematic review of electronic databases (CINAHL; EMBASE; PsychInfo; MEDLINE; ASSIA and CENTRAL), supplemented by expert contact, reference and citation checking, and grey literature searches. Published and unpublished studies will be eligible for inclusion with no limitations placed on year of publication. Primary outcomes of interest will be standardised measurements of depression, anxiety, psychological distress or mental health-related quality of life. Eligibility and randomisation proportions will be calculated as secondary outcomes. If data permits, meta-analytical techniques will examine: (1) overall effectiveness of psychological interventions for people with dementia or mild cognitive impairment in relation to outcomes of depression, anxiety, psychological distress or mental health-related quality of life; (2) clinical and methodological moderators associated with effectiveness; (3) proportions eligible, recruited and randomised. ETHICS AND DISSEMINATION: Ethical approval is not required for the present systematic review. Results will inform the design of a feasibility study examining a new psychological intervention for people with dementia and depression, with dissemination through publication in peer-reviewed journals and presentations at relevant conferences. TRIAL REGISTRATION NUMBER: CRD42015025177. PMID- 26817639 TI - School-based intervention for the prevention of HPV among adolescents: a cluster randomised controlled study. AB - OBJECTIVE: To improve primary prevention of human papillomavirus (HPV) infection by promoting vaccination and increased condom use among upper secondary school students. DESIGN: Cluster randomised controlled trial. SETTING: 18 upper secondary schools in Sweden. PARTICIPANTS: Schools were first randomised to the intervention or the control group, after which individual classes were randomised so as to be included or not. Of the 832 students aged 16 years invited to participate during the regular individual health interview with the school nurse, 751 (90.2%) agreed to participate and 741 (89.1%) students completed the study. INTERVENTIONS: The intervention was based on the Health Belief Model (HBM). According to HBM, a person's health behaviour can be explained by individual beliefs regarding health actions. School nurses delivered 30 min face-to-face structured information about HPV, including cancer risks and HPV prevention, by propagating condom use and HPV vaccination. Students in the intervention and the control groups completed questionnaires at baseline and after 3 months. MAIN OUTCOME MEASURES: Intention to use condom with a new partner and beliefs about primary prevention of HPV, and also specifically vaccination status and increased condom use. RESULTS: All statistical analyses were performed at the individual level. The intervention had a significant effect on the intention to use condom (p=0.004). There was also a significant effect on HBM total score (p=0.003), with a 2.559 points higher score for the intervention group compared to the controls. The influence on the HBM parameters susceptibility and severity was also significant (p<0.001 for both variables). The intervention also influenced behaviour: girls in the intervention group chose to have themselves vaccinated to a significantly higher degree than the controls (p=0.02). No harms were reported. CONCLUSIONS: The school-based intervention had favourable effects on the beliefs about primary prevention of HPV, and increased the HPV vaccination rates in a diverse population of adolescents. TRIAL REGISTRATION NUMBER: NCT02280967; Results. PMID- 26817640 TI - Assessing herd immunity against rubella in Japan: a retrospective seroepidemiological analysis of age-dependent transmission dynamics. AB - OBJECTIVE: We aimed to epidemiologically assess rubella herd immunity as a function of time, age and gender in Japan, with reference to the recent 2012-2014 rubella epidemic. DESIGN: This study is a retrospective seroepidemiological analysis. MAIN OUTCOME MEASURES: The susceptible fraction of the population was examined as a function of age and time. The age at infection was assessed using reported case data. RESULTS: Whereas 30 years ago rubella cases were seen only among children, the median (25-75th centiles) age of cases in 2014 was elevated to 32.0 (17.0-42.0) years among males and 27.0 (7.0-37.0) years among females. Susceptible pockets among male birth cohorts 1989-1993 and 1974-1978 were identified, with seropositive proportions of 70.0% and 68.0%, respectively. The majority of female age groups had greater seropositive proportions than the herd immunity threshold, with a minor susceptible pocket for those born from 1989 to 1993 (78.3% seropositive). The age-standardised seronegative proportion decreased to 18.3% (95% CI 16.8% to 19.8%) among males and 15.6% (95% CI 10.0% to 21.2%) among females in 2013, and the immune fraction was not sufficiently below the herd immunity threshold. While the number of live births born to susceptible mothers in 1983 was estimated at 171,876 across Japan, in 2013 it was reduced to 23,698. CONCLUSIONS: An elevated age at rubella virus infection and the presence of susceptible pockets among adults were observed in Japan. Although, overall, the absolute number of rubella cases has steadily declined in Japan, the elevated age of rubella cases, along with increased numbers of susceptible adults, contributed to the observation of as many as 45 congenital rubella syndrome (CRS) cases, which calls for supplementary vaccination among susceptible adults. Assessing herd immunity is considered essential for routinely monitoring the risk of future rubella epidemics and CRS cases. PMID- 26817641 TI - Decisions about the use of psychotropic medication during pregnancy: a qualitative study. AB - OBJECTIVE: To understand the perspectives of women with severe mental illness concerning the use of psychotropic medicines while pregnant. DESIGN: Interviews conducted by female peer researchers with personal experience of making or considering decisions about using psychotropic medicines in pregnancy, supported by professional researchers. PARTICIPANTS: 12 women who had had a baby in the past 5 years and had taken antipsychotics or mood-stabilisers for severe mental illness within the 12-month period immediately prior to that pregnancy. Recruitment to the study was via peer networks and the women interviewed came from different regions of England. SETTING: Interviews were arranged in places where women felt comfortable and that accommodated their childcare needs including their home, local library and the research office. RESULTS: The views expressed demonstrated complex attempts to engage with decision-making about the use of psychotropic medicines in pregnancy. In nearly all cases, the women expressed the view that healthcare professionals had access to limited information leaving women to rely on experiential and common sense evidence when making decisions about medicine taking during pregnancy. CONCLUSIONS: The findings complement existing work using electronic health records by providing explanations for the discontinuation of psychotropic medicines in pregnancy. Further work is necessary to understand health professionals' perspectives on the provision of services and care to women with severe mental illness during pregnancy. PMID- 26817642 TI - A study protocol for a randomised controlled trial evaluating clinical effects of platelet transfusion products: the Pathogen Reduction Evaluation and Predictive Analytical Rating Score (PREPAReS) trial. AB - INTRODUCTION: Patients with chemotherapy-induced thrombocytopaenia frequently experience minor and sometimes severe bleeding complications. Unrestrictive availability of safe and effective blood products is presumed by treating physicians as well as patients. Pathogen reduction technology potentially offers the opportunity to enhance safety by reducing bacterial and viral contamination of platelet products along with a potential reduction of alloimmunisation in patients receiving multiple platelet transfusions. METHODS AND ANALYSIS: To test efficacy, a randomised, single-blinded, multicentre controlled trial was designed to evaluate clinical non-inferiority of pathogen-reduced platelet concentrates treated by the Mirasol system, compared with standard plasma-stored platelet concentrates using the percentage of patients with WHO grade >= 2 bleeding complications as the primary endpoint. The upper limit of the 95% CI of the non inferiority margin was chosen to be a <= 12.5% increase in this percentage. Bleeding symptoms are actively monitored on a daily basis. The adjudication of the bleeding grade is performed by 3 adjudicators, blinded to the platelet product randomisation as well as by an automated computer algorithm. Interim analyses evaluating bleeding complications as well as serious adverse events are performed after each batch of 60 patients. The study started in 2010 and patients will be enrolled up to a maximum of 618 patients, depending on the results of consecutive interim analyses. A flexible stopping rule was designed allowing stopping for non-inferiority or futility. Besides analysing effects of pathogen reduction on clinical efficacy, the Pathogen Reduction Evaluation and Predictive Analytical Rating Score (PREPAReS) is designed to answer several other pending questions and translational issues related to bleeding and alloimmunisation, formulated as secondary and tertiary endpoints. ETHICS AND DISSEMINATION: Ethics approval was obtained in all 3 participating countries. Results of the main trial and each of the secondary endpoints will be submitted for publication in a peer reviewed journal. TRIAL REGISTRATION NUMBER: NTR2106; Pre-results. PMID- 26817644 TI - Gain control mechanisms in the nociceptive system. AB - The "gate control theory of pain" of 1965 became famous for integrating clinical observations and the understanding of spinal dorsal horn circuitry at that time into a testable model. Although it became rapidly clear that spinal circuitry is much more complex than that proposed by Melzack and Wall, their prediction of the clinical efficacy of transcutaneous electrical nerve stimulation and spinal cord stimulation has left an important clinical legacy also 50 years later. In the meantime, it has been recognized that the sensitivity of the nociceptive system can be decreased or increased and that this "gain control" can occur at peripheral, spinal, and supraspinal levels. The resulting changes in pain sensitivity can be rapidly reversible or persistent, highly localized or widespread. Profiling of spatio-temporal characteristics of altered pain sensitivity (evoked pain to mechanical and/or heat stimuli) allows implications on the mechanisms likely active in a given patient, including peripheral or central sensitization, intraspinal or descending inhibition. This hypothesis generation in the diagnostic process is an essential step towards a mechanism based treatment of pain. The challenge now is to generate the rational basis of multimodal pain therapy algorithms by including profile-based stratification of patients into studies on efficacy of pharmacological and nonpharmacological treatment modalities. This review outlines the current evidence base for this approach. PMID- 26817643 TI - Protocol for PIT: a phase III trial of prophylactic irradiation of tracts in patients with malignant pleural mesothelioma following invasive chest wall intervention. AB - INTRODUCTION: Histological diagnosis of malignant mesothelioma requires an invasive procedure such as CT-guided needle biopsy, thoracoscopy, video-assisted thorascopic surgery (VATs) or thoracotomy. These invasive procedures encourage tumour cell seeding at the intervention site and patients can develop tumour nodules within the chest wall. In an effort to prevent nodules developing, it has been widespread practice across Europe to irradiate intervention sites postprocedure--a practice known as prophylactic irradiation of tracts (PIT). To date there has not been a suitably powered randomised trial to determine whether PIT is effective at reducing the risk of chest wall nodule development. METHODS AND ANALYSIS: In this multicentre phase III randomised controlled superiority trial, 374 patients who can receive radiotherapy within 42 days of a chest wall intervention will be randomised to receive PIT or no PIT. Patients will be randomised on a 1:1 basis. Radiotherapy in the PIT arm will be 21 Gy in three fractions. Subsequent chemotherapy is given at the clinicians' discretion. A reduction in the incidence of chest wall nodules from 15% to 5% in favour of radiotherapy 6 months after randomisation would be clinically significant. All patients will be followed up for up to 2 years with monthly telephone contact and at least four outpatient visits in the first year. ETHICS AND DISSEMINATION: PIT was approved by NRES Committee North West-Greater Manchester West (REC reference 12/NW/0249) and recruitment is currently on-going, the last patient is expected to be randomised by the end of 2015. The analysis of the primary end point, incidence of chest wall nodules 6 months after randomisation, is expected to be published in 2016 in a peer reviewed journal and results will also be presented at scientific meetings and summary results published online. A follow-up analysis is expected to be published in 2018. TRIAL REGISTRATION NUMBER: ISRCTN04240319; NCT01604005; Pre-results. PMID- 26817645 TI - Preclinical Study of a Combination of Erlotinib and Bevacizumab in Early Stages of Unselected Non-Small Cell Lung Cancer Patient-Derived Xenografts. AB - BACKGROUND: The differential outcomes of clinical studies of the targeted therapies for non-small cell lung cancer (NSCLC) indicate that better stratification of patients is required. This could be achieved with the help of patient-derived xenografts (PDX) of epidermal growth factor receptor (EGFR) wild type patients resistant to erlotinib treatment. OBJECTIVE: To explore the potential of patient-derived NSCLC xenografts to optimize therapy using 24 well characterized early-stage NSCLC PDX. METHOD: Patient tumor tissue was transplanted subcutaneously into nude mice. After engraftment, tumors were expanded and the sensitivity was tested. Gene expression analysis was used to identify differentially expressed genes between erlotinib responder (n = 3) and non-responder (n = 21). Tumor tissue was analyzed with TaqMan PCR, immunohistochemistry and ELISA to examine the response of the models. RESULTS: Gene expression analysis revealed vascular endothelial growth factor A (VEGFA) to be up-regulated in erlotinib non-responder. Because of that, the combination of erlotinib with bevacizumab was evaluated in one erlotinib-sensitive and four erlotinib-resistant PDX. Combination treatment was superior to monotherapy, leading to the highest and significant inhibition of tumor growth in all models investigated. A decline of VEGFA protein and an increase of VEGFA-mRNA were observed after bevacizumab treatment. Bevacizumab treatment resulted in a distinct decrease of blood vessel number. CONCLUSION: This study showed that with the help of preclinical PDX models, drug combinations for therapy improvement can be identified on a rational basis. It was observed that a dual blockage of EGFR and VEGFA was more effective than a monotherapy for the treatment of NSCLC in selected PDX models. PDX could be employed to optimize the treatment of cancer patients. PMID- 26817647 TI - Resistance to PPO-inhibiting herbicide in Palmer amaranth from Arkansas. AB - BACKGROUND: The widespread occurrence of ALS inhibitor- and glyphosate-resistant Amaranthus palmeri has led to increasing use of protoporphyrinogen oxidase (PPO) inhibiting herbicides in cotton and soybean. Studies were conducted to confirm resistance to fomesafen (a PPO inhibitor), determine the resistance frequency, examine the resistance profile to other foliar-applied herbicides and investigate the resistance mechanism of resistant plants in a population collected in 2011 (AR11-LAW B) and its progenies from two cycles of fomesafen selection (C1 and C2). RESULTS: The frequency of fomesafen-resistant plants increased from 5% in the original AR11-LAW-B to 17% in the C2 population. The amounts of fomesafen that caused 50% growth reduction were 6-, 13- and 21-fold greater in AR11-LAW-B, C1 and C2 populations, respectively, than in the sensitive ecotype. The AR11-LAW B population was sensitive to atrazine, dicamba, glufosinate, glyphosate and mesotrione but resistant to ALS-inhibiting herbicides pyrithiobac and trifloxysulfuron. Fomesafen survivors from C1 and C2 populations tested positive for the PPO glycine 210 deletion previously reported in waterhemp (Amaranthus tuberculatus). CONCLUSION: These studies confirmed that Palmer amaranth in Arkansas has evolved resistance to foliar-applied PPO-inhibiting herbicide. PMID- 26817646 TI - Zinc supplementation ameliorates glycoprotein components and oxidative stress changes in the lung of streptozotocin diabetic rats. AB - Zinc (Zn) is a component of numerous enzymes that function in a wide range of biological process, including growth, development, immunity and intermediary metabolism. Zn may play a role in chronic states such as cardiovascular disease and diabetes mellitus. Zn acts as cofactor and for many enzymes and proteins and has antioxidant, antiinflammatory and antiapoptotic effects. Taking into consideration that lung is a possible target organ for diabetic complications, the aim of this study was to investigate the protective role of zinc on the glycoprotein content and antioxidant enzyme activities of streptozotocin (STZ) induced diabetic rat tissues. Female Swiss albino rats were divided into four groups. Group I, control; Group II, control + zinc sulfate; Group III, STZ diabetic; Group IV, diabetic + zinc sulfate. Diabetes was induced by intraperitoneal injection of STZ (65 mg/kg body weight). Zinc sulfate was given daily by gavage at a dose of 100 mg/kg body weight every day for 60 days to groups II and IV. At the last day of the experiment, rats were sacrificed, lung tissues were taken. Also, glycoprotein components, tissue factor (TF) activity, protein carbonyl (PC), advanced oxidative protein products (AOPP), hydroxyproline, and enzyme activities in lung tissues were determined. Glycoprotein components, TF activity, lipid peroxidation, non enzymatic glycation, PC, AOPP, hydroxyl proline, lactate dehydrogenase, catalase, superoxide dismutase, myeloperoxidase, xanthine oxidase, adenosine deaminase and prolidase significantly increased in lung tissues of diabetic rats. Also, glutathione levels, paraoxonase, arylesterase, carbonic anhydrase, and Na(+)/K(+) ATPase activities were decreased. Administration of zinc significantly reversed these effects. Thus, the study indicates that zinc possesses a significantly beneficial effect on the glycoprotein components and oxidant/antioxidant enzyme activities. PMID- 26817648 TI - Evaluating the effectiveness of a self-management exercise intervention on wound healing, functional ability and health-related quality of life outcomes in adults with venous leg ulcers: a randomised controlled trial. AB - Exercise that targets ankle joint mobility may lead to improvement in calf muscle pump function and subsequent healing. The objectives of this research were to assess the impact of an exercise intervention in addition to routine evidence based care on the healing rates, functional ability and health-related quality of life for adults with venous leg ulcers (VLUs). This study included 63 patients with VLUs. Patients were randomised to receive either a 12-week exercise intervention with a telephone coaching component or usual care plus telephone calls at the same timepoints. The primary outcome evaluated the effectiveness of the intervention in relation to wound healing. The secondary outcomes evaluated physical activity, functional ability and health-related quality of life measures between groups at the end of the 12 weeks. A per protocol analysis complemented the effectiveness (intention-to-treat) analysis to highlight the importance of adherence to an exercise intervention. Intention-to-treat analyses for the primary outcome showed 77% of those in the intervention group healed by 12 weeks compared to 53% of those in the usual care group. Although this difference was not statistically significant due to a smaller than expected sample size, a 24% difference in healing rates could be considered clinically significant. The per protocol analysis for wound healing, however, showed that those in the intervention group who adhered to the exercise protocol 75% or more of the time were significantly more likely to heal and showed higher rates for wound healing than the control group (P = 0.01), that is, 95% of those who adhered in the intervention group healed in 12 weeks. The secondary outcomes of physical activity, functional ability and health-related quality of life were not significantly altered by the intervention. Among the secondary outcomes (physical activity, functional ability and health-related quality of life), intention-to treat analyses did not support the effectiveness of the intervention. However, per protocol analyses revealed encouraging results with those participants who adhered more than 75% of the time (n = 19) showing significantly improved Range of Ankle Motion from the self-management exercise programme (P = 0.045). This study has shown that those participants who adhere to the exercise programme as an adjunctive treatment to standard care are more likely to heal and have better functional outcomes than those who do not adhere to the exercises in conjunction with usual care. PMID- 26817649 TI - Injury to Azygos Venous System: A Co-Existing Injury in High-Impact Lethal Trauma. AB - BACKGROUND: About 50 cases of azygos venous system injuries following civilian trauma have been published in current literature. The purpose of our study was to investigate the incidence of these injuries, the causative mechanism and type of trauma, the co-existing injuries, and the mortality rate in our institution. METHODS: We performed a retrospective review of all trauma patients who were admitted to the surgical department of the General Hospital of Rethymno during an 11-year period. Our study included patients arriving at our institution dead or alive with an azygos venous system injury following blunt or penetrating civilian trauma. RESULTS: Seven patients-five men and two women-were identified with azygos venous system injuries. Five had an azygos vein laceration, one suffered from both azygos and hemiazygos vein lacerations, and the last one had sustained hemiazygos and accessory hemiazygos vein injuries. All of them suffered from a blunt trauma. Three arrived at our hospital in extremis, and all died within 24 h despite our resuscitation attempts. All of our patients were polytrauma patients. All of them had co-existing torso injuries which were severe in all but one case, three of them suffered also from serious head injuries, and all but one had at least serious extremity's injuries. CONCLUSION: Azygos venous system injuries are rare, although it seems that they are more frequent than current literature would indicate. Blunt trauma mechanism seems to be predominant in civilian trauma setting, and the patients have usually sustained a lot of serious and severe co existing injuries with high resultant lethality. PMID- 26817650 TI - Severity of Recurrent Laryngeal Nerve Injuries in Thyroid Surgery. AB - BACKGROUND: Few studies in the literature have reported recovery data for different types of recurrent laryngeal nerve injuries (RLNIs). This study is the first attempt to classify RLNIs and rank them by severity. METHODS: This prospective clinical study analyzed 281 RLNIs in which a true loss of signal was identified by intraoperative neuromonitoring (IONM), and vocal cord palsy (VCP) was confirmed by a postoperative laryngoscope. For each injury type, the prevalence of VCP, the time of VCP recovery, and physical changes on nerves were analyzed. Additionally, different RLNI types were experimentally induced in a porcine model to compare morphological change. RESULTS: The overall VCP rate in at-risk patients/nerves was 8.9/4.6 %, respectively. The distribution of RLNI types, in order of frequency, was traction (71 %), thermal (17 %), compression (4.2 %), clamping (3.4 %), ligature entrapment (1.6 %), suction (1.4 %), and nerve transection (1.4 %). Complete recovery from VCP was documented in 91 % of RLNIs. Recovery time was significantly faster in the traction group compared to the other groups (p < 0.001). The rates of temporary and permanent VCP were 98.6 and 1.4 % for traction lesion, 72 and 28 % for thermal injury, 100 and 0 % for compression injury, 50 and 50 % for clamping injury, 100 and 0 % for ligature entrapment, 100 and 0 % for suction injury, and 0 and 100 % for nerve transection, respectively. Physical changes were noted in 14 % of RLNIs in which 56 % of VCP was permanent. However, among the remaining 86 % IONM-detectable RLNIs without physical changes, only 1.2 % of VCP was permanent. A porcine model of traction lesion showed only distorted outer nerve structure, whereas the thermal lesion showed severe damage in the inner endoneurium. CONCLUSIONS: Different RNLIs induce different morphological alterations and have different recovery outcomes. Permanent VCP is rare in lesions that are visually undetectable but detectable by IONM. By enabling early detection of RLNI and prediction of outcome, IONM can help clinicians plan intra- and postoperative treatment. PMID- 26817651 TI - Preoperative Pneumonia and Postoperative Venous Thrombosis: A Cohort Study of 427,656 Patients Undergoing Major General Surgery. AB - BACKGROUND: The literature is sparse regarding the association between pneumonia and venous thrombosis in surgical patients. The aim of this study was to investigate the risk of postoperative venous thrombosis in patients who fit the criteria for preoperative pneumonia using data from the ongoing American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database while adjusting for potential confounders. METHODS: This is a cohort study using data from the ACS NSQIP database participating sites from 2008 (211 sites) and 2009 (237 sites). 427,656 patients undergoing major general surgery were included. The 30-day risk of postoperative venous thrombosis including deep vein thrombosis (DVT) and pulmonary embolism (PE) was evaluated in patients with preoperative pneumonia diagnosed before undergoing major general surgery. RESULTS: Patients with preoperative pneumonia had a higher incidence of both 30 day DVT and PE than patients without preoperative pneumonia. After adjusting for all potential confounders, the effect estimates for the association between preoperative pneumonia and venous thrombosis were DVT, OR: 1.67 (95% CI 1.32 2.11) and PE, OR: 2.18 (95% CI 1.48-3.22). CONCLUSIONS: A large, multicenter database of surgical patients showed that preoperative pneumonia may increase risk for developing venous thrombosis. This adds to our understanding of risk factors for venous thrombosis and suggests a potential benefit of diagnosing preoperative pneumonia in patients undergoing major general surgery. PMID- 26817652 TI - Anatomical Resection But Not Surgical Margin Width Influence Survival Following Resection for HCC, A Propensity Score Analysis. AB - BACKGROUND: The effects of the surgical resection margin on the clinical outcomes in hepatocellular carcinoma (HCC) cases remain controversial. The objective of this study was to further examine this issue. METHODS: The details of all HCC patients who underwent hepatectomy between December 1999 and December 2009 at the Division of Hepatobiliary and Pancreas Surgery, Asan Medical Center were analyzed retrospectively. We divided 1022 HCC patients into two groups according to the most significant surgical margin length. To overcome any bias due to differences in the distribution of covariates between the two groups, the patients were in a matched 1:1 ratio by propensity score analysis. RESULTS: A surgical margin <=1 mm was identified as the most significant surgical margin in both disease-free survival (DFS) and overall survival (OS) (p = 0.008 and p = 0.026, respectively). However, many clinicopathological factors were different between the resection margin <=1 mm and >1 mm groups. To reduce these different clinicopathological factors, propensity score matching was performed using 21 selected factors. After matching, no significant difference was found in DFS and OS between the two groups (p = 0.688, p = 0.398). In addition, there was no significant difference in the intrahepatic recurrence rate and pattern between the resection margin groups. Except for the preoperative patient's status and tumor stage, significant risk factors in OS were anatomical resection and postoperative morbidity (p = 0.002, p = 0.001). CONCLUSION: We identified that the widths of the resection margin in resectable hepatocellular carcinoma did not influence the postoperative recurrence rates, overall survival, and recurrence pattern in multivariable analysis as well as propensity score match analysis. PMID- 26817653 TI - [Pain, agitation and delirium in acute respiratory failure]. AB - Avoiding pain, agitation and delirium as well as avoiding unnecessary deep sedation is a powerful yet challenging strategy in critical care medicine. A number of interactions between cerebral function and respiratory function should be regarded in patients with respiratory failure and mechanical ventilation. A cooperative sedation strategy (i.e. patient is awake and free of pain and delirium) is feasible in many patients requiring invasive mechanical ventilation. Especially patients with mild acute respiratory distress syndrome (ARDS) seem to benefit from preserved spontaneous breathing. While completely disabling spontaneous ventilation with or without neuromuscular blockade is not a standard strategy in ARDS, it might be temporarily required in patients with severe ARDS, who have substantial dyssynchrony or persistent hypoxaemia. Since pain, agitation and delirium compromise respiratory function they should also be regarded during noninvasive ventilation and during ventilator weaning. Pharmacological sedation can have favourable effects in these situations, but should not be given routinely or uncritically. PMID- 26817655 TI - A comparison of THI indices leads to a sensible heat-based heat stress index for shaded cattle that aligns temperature and humidity stress. AB - The combined temperature-humidity heat stress is estimated in farm animals by indices derived of an index based on human thermal comfort sensation. The latter index consists of temperature and humidity measures that sum to form the temperature-humidity index (THI). The hitherto unknown relative contribution of temperature and humidity to the THI was examined. A temperature-humidity data set (temperature 20-42 degrees C and relative humidity 10-70 %) was used to assess by regression procedures the relative weights of temperature and humidity in the variance of THI values produced by six commonly used heat stress indices. The temperature (Ta) effect was predominant (0.82-0.95 of variance) and humidity accounted for only 0.05 to 0.12 of THI variance, half of the variance encountered in animal responses to variable humidity heat stress. Significant difference in THI values was found between indices in the relative weights of temperature and humidity. As in THI indices, temperature and humidity are expressed in different physical units, their sum has no physical attributes, and empirical evaluations assess THI relation to animal responses. A sensible heat THI was created, in which at higher temperatures humidity reaches 0.25 of sensible heat, similarly to evaporative heat loss span in heat stressed animals. It relates to ambient temperature-humidity similarly to present THI; its values are similar to other THI but greater at higher humidity. In warm conditions, mean animal responses are similar in both indices. The higher sensitivity to humidity makes this index preferable for warm-humid conditions. PMID- 26817656 TI - A Radical Sodium Reduction Policy is not Supported by Randomized Controlled Trials or Observational Studies: Grading the Evidence. AB - Several health institutions recommend sodium intake be reduced to below 2,300 mg, which means that 6-7 billion individuals should alter their diet to accommodate. Such a radical recommendation should be based on solid evidence. However, this review reveals that (i) there are no randomized controlled trials (RCTs) allocating individuals to below 2,300 mg and measuring health outcomes; (ii) RCTs allocating risk groups such as obese prehypertensive individuals and hypertensive individuals down to (but not below) 2,300 mg show no effect of sodium reduction on all-cause mortality; (iii) RCTs allocating individuals to below 2,300 mg show a minimal effect on blood pressure in the healthy population (less than 1mm Hg) and significant increases in renin, aldosterone, noradrenalin cholesterol, and triglyceride; and (iv) observational studies show that sodium intakes below 2,645 and above 4,945 mg are associated with increased mortality. Given that 90% of the worlds' population currently consumes sodium within the optimal range of 2,645 4,945 mg, there is no scientific basis for a public health recommendation to alter sodium intake. PMID- 26817654 TI - Direction of Association Between Depressive Symptoms and Lifestyle Behaviors in Patients with Coronary Heart Disease: the Heart and Soul Study. AB - BACKGROUND: Emerging evidence indicates that the association between depression and subsequent cardiovascular events is largely mediated by health behaviors. However, it is unclear whether depression is the cause or the consequence of poor health behaviors. PURPOSE: The purpose of the present study is to examine prospective, bidirectional relationships of depressive symptoms with behavioral and lifestyle factors among patients with coronary heart disease. METHODS: Depressive symptoms and lifestyle behaviors (physical activity, medication adherence, body mass index, waist to hip ratio, sleep quality, and smoking status) were assessed at baseline and 5 years later among a prospective cohort of 667 patients with stable coronary heart disease. RESULTS: Greater depressive symptoms at baseline predicted poorer lifestyle behaviors 5 years later (less physical activity, lower medication adherence, higher body mass index, higher waist to hip ratio, worse sleep quality, and smoking). After adjustment for demographics, cardiac disease severity, comorbidity, and baseline lifestyle behaviors, depressive symptom severity remained predictive of subsequent worsening of physical activity (beta = -0.08; 95 % confidence interval (CI) = 0.16, -0.01; p = 0.03), medication adherence (beta = -0.16; 95 % CI = -0.24, 0.08; p < 0.001), and sleep quality (beta = -0.19; 95 % CI = -0.27, -0.11; p < 0.001). Baseline lifestyle behaviors also predicted 5-year change in depressive symptoms, although the associations were attenuated after adjustment for baseline depressive symptoms and covariates. CONCLUSIONS: Among patients with coronary heart disease, depressive symptoms were linked to a range of lifestyle risk factors and predicted further declines in physical activity, medication adherence, and sleep quality. PMID- 26817658 TI - In vivo dermal absorption of pyrethroid pesticides in the rat. AB - Exposure to pyrethroid pesticides is a potential cause for concern. The objective of this study was to examine the in vivo dermal absorption of bifenthrin, deltamethrin, and permethrin in the rat. Dorsal hair on adult male Long-Evans rats was removed. The next day, the skin was dosed with 1750 nmol (312.5 nmol/cm(2)) of radiolabeled (5 uCi) bifenthrin, deltamethrin, or permethrin in acetone. A nonoccluding plastic cover was glued over the dosing site. The animals were placed in metabolism cages to collect excreta. At 24 h postdosing, the skin was washed with soap and water, and rats in one group were euthanized and their tissues were collected. The skin was removed and tape stripped. The remaining animals were returned to the metabolism cages after the wash for 4 d. These rats were then euthanized and handled as already described. Excreta, wash, tape strips, tissues, and carcass were analyzed for pyrethroid-derived radioactivity. The wash and tape strips removed >50% of the dose and skin retained 9-24%. Cumulative radioactivity in excreta was 0.5-7% at 24 h and 3-26% at 120 h. Radioactivity in tissues was <0.3% of the dose, while carcass retained 2 to 5%. Assuming absorption equals cumulative recovery in skin (washed and tape stripped), excreta, tissues, and carcass, absorption was permethrin ~ bifenthrin > deltamethrin at 24 h and permethrin > deltamethrin > bifenthrin at 120 h. Using the parallelogram approach with published in vitro data, human dermal absorption of these pyrethroids was estimated to be <10% of the dose. PMID- 26817657 TI - Efficient Covalent Bond Formation in Gas-Phase Peptide-Peptide Ion Complexes with the Photoleucine Stapler. AB - Noncovalent complexes of hydrophobic peptides GLLLG and GLLLK with photoleucine (L*) tagged peptides G(L* n L m )K (n = 1,3, m = 2,0) were generated as singly charged ions in the gas phase and probed by photodissociation at 355 nm. Carbene intermediates produced by photodissociative loss of N2 from the L* diazirine rings underwent insertion into X-H bonds of the target peptide moiety, forming covalent adducts with yields reaching 30%. Gas-phase sequencing of the covalent adducts revealed preferred bond formation at the C-terminal residue of the target peptide. Site-selective carbene insertion was achieved by placing the L* residue in different positions along the photopeptide chain, and the residues in the target peptide undergoing carbene insertion were identified by gas-phase ion sequencing that was aided by specific (13)C labeling. Density functional theory calculations indicated that noncovalent binding to GL*L*L*K resulted in substantial changes of the (GLLLK + H)(+) ground state conformation. The peptide moieties in [GL*L*LK + GLLLK + H](+) ion complexes were held together by hydrogen bonds, whereas dispersion interactions of the nonpolar groups were only secondary in ground-state 0 K structures. Born-Oppenheimer molecular dynamics for 100 ps trajectories of several different conformers at the 310 K laboratory temperature showed that noncovalent complexes developed multiple, residue-specific contacts between the diazirine carbons and GLLLK residues. The calculations pointed to the substantial fluidity of the nonpolar side chains in the complexes. Diazirine photochemistry in combination with Born-Oppenheimer molecular dynamics is a promising tool for investigations of peptide-peptide ion interactions in the gas phase. Graphical Abstract ?. PMID- 26817659 TI - Rethinking the Well Woman Visit: A Scoping Review to Identify Eight Priority Areas for Well Woman Care in the Era of the Affordable Care Act. AB - PURPOSE: The annual pap smear for cervical cancer screening, once a mainstay of the well woman visit (WWV), is no longer recommended for most low-risk women. This change has led many women and their health care providers to wonder if they should abandon this annual preventive health visit altogether. Changing guidelines coinciding with expanded WWV coverage for millions of American women under the Patient Protection and Affordable Care Act have created confusion for health care consumers and care givers alike. Is there evidence to support continued routine preventive health visits for women and, if so, what would ideally constitute the WWV of today? METHODS: A scoping review of the literature was undertaken to appraise the current state of evidence regarding a wide range of possible elements to identify priority areas for the WWV. FINDINGS: A population health perspective taking into consideration the reproductive health needs of women as well as the preventable and modifiable leading causes of death and disability was used to identify eight domains for the WWV of today: 1) reproductive life planning and sexual health, 2) cardiovascular disease and stroke, 3) prevention, screening, and early detection of cancers, 4) unintended injury, 5) anxiety, depression, substance abuse, and suicidal intent, 6) intimate partner violence, assault, and homicide, 7) lower respiratory disease, and 8) arthritis and other musculoskeletal problems. CONCLUSIONS: The WWV remains a very important opportunity for prevention, health education, screening, and early detection and should not be abandoned. PMID- 26817662 TI - Fibrinogen Reduction and Motor Function Improvement by Hematopoietic Growth Factor Treatment in Chronic Stroke in Aged Mice: A Treatment Frequency Study. AB - Stroke is a serious medical condition that causes long-term neurological disability in mainly elderly adults worldwide. Lack of therapy to improve functional recovery in the chronic phase of stroke is a major challenge for stroke research. Combining two hematopoietic growth factors, stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF), our previous studies have demonstrated the neurovascular restorative efficacy of this treatment in the chronic phase of experimental stroke. Elevated plasma fibrinogen has been thought to serve as a predictor for ischemic stroke. Here we have determined the treatment frequency in reducing plasma fibrinogen and in restoring motor function in aged mice with chronic stroke. Our findings show that SCF + G-CSF treatment in chronic stroke decreases plasma fibrinogen and improves motor function in aged mice. No differences have been found between a 2-week treatment regimen and 7-day treatment in the plasma fibrinogen assay, while the 7-day treatment regimen displays a better recovery pattern with regard to motor function. This study provides new insight into understanding the potential contribution of SCF + G-CSF in both reducing the risk of recurrent ischemic stroke and enhancing stroke recovery. PMID- 26817661 TI - Tape Stripping Technique for Stratum Corneum Protein Analysis. AB - The aim of this study was to investigate the amount of protein in stratum corneum in atopic dermatitis (AD) patients and healthy controls, using tape stripping technique. Furthermore, to compare two different methods for protein assessment. Tape stripping was performed in AD patients and healthy controls to collect stratum corneum samples and subsequently analysed with two different methods: Squame Scan, which gives an estimate of total protein (soluble and insoluble) and Micro BCA protein determination kit which measures soluble protein. Significant differences in cumulative protein content between AD lesional, AD non-lesional and healthy control skin was found using the Squame Scan as well as the Micro BCA protein determination kit. AD patients had significantly lower amount of protein, both total protein and soluble protein compared to healthy controls. Furthermore, soluble protein formed 82% of total protein in AD lesional skin, compared to 17 24% for AD non-lesional skin and healthy control. A decreasing amount of total protein with increasing stratum corneum depth was found for all skin types. Significant differences in stratum corneum protein content between AD lesional, AD non-lesional and healthy control skin were revealed, independent of method used. PMID- 26817663 TI - All-atom molecular dynamics analysis of multi-peptide systems reproduces peptide solubility in line with experimental observations. AB - In order to investigate the contribution of individual amino acids to protein and peptide solubility, we carried out 100 ns molecular dynamics (MD) simulations of 10(6) A(3) cubic boxes containing ~3 * 10(4) water molecules and 27 tetra peptides regularly positioned at 23 A from each other and composed of a single amino acid type for all natural amino acids but cysteine and glycine. The calculations were performed using Amber with a standard force field on a special purpose MDGRAPE-3 computer, without introducing any "artificial" hydrophobic interactions. Tetra-peptides composed of I, V, L, M, N, Q, F, W, Y, and H formed large amorphous clusters, and those containing A, P, S, and T formed smaller ones. Tetra-peptides made of D, E, K, and R did not cluster at all. These observations correlated well with experimental solubility tendencies as well as hydrophobicity scales with correlation coefficients of 0.5 to > 0.9. Repulsive Coulomb interactions were dominant in ensuring high solubility, whereas both Coulomb and van der Waals (vdW) energies contributed to the aggregations of low solubility amino acids. Overall, this very first all-atom molecular dynamics simulation of a multi-peptide system appears to reproduce the basic properties of peptide solubility, essentially in line with experimental observations. PMID- 26817660 TI - Membrane dynamics associated with viral infection. AB - Viral replication and spreading are fundamental events in the viral life cycle, accounting for the assembly and egression of nascent virions, events that are directly associated with viral pathogenesis in target hosts. These processes occur in cellular compartments that are modified by specialized viral proteins, causing a rearrangement of different cell membranes in infected cells and affecting the ER, mitochondria, Golgi apparatus, vesicles and endosomes, as well as processes such as autophagic membrane flux. In fact, the activation or inhibition of membrane trafficking and other related activities are fundamental to ensure the adequate replication and spreading of certain viruses. In this review, data will be presented that support the key role of membrane dynamics in the viral cycle, especially in terms of the assembly, egression and infection processes. By defining how viruses orchestrate these events it will be possible to understand how they successfully complete their route of infection, establishing viral pathogenesis and provoking disease. PMID- 26817664 TI - Associations between conflictual relationships, psychopathology, and the use of psychotropic drugs among older people living in residential facilities. AB - BACKGROUND: Psychiatric symptoms and conflictual relationships (CR) may negatively affect the delivery of care in residential facilities (RF). This study aims to analyze neuropsychiatric symptoms, their correlations with CR among older people living in RF, and their associations with the prescription of psychotropic drugs. METHODS: A total of 1215 RF residents in five Italian regions were selected for this cross-sectional study. Psychiatric symptoms and CR were assessed with the Neuropsychiatric Inventory and the Resident Assessment Instrument, respectively. Associations between Neuropsychiatric Inventory items, CR, and the use of psychotropic drugs were tested via multiple logistic regressions. RESULTS: About half (52.7%) of the RF residents experienced one or more clinically relevant neuropsychiatric symptoms. At least one category of CR was reported for 223 residents (19%). Although reciprocal associations were found between different categories of CR, only conflictuality with other residents was associated with the use of antipsychotics (odds ratio (OR) = 2.12). Significant associations were found with irritability (with staff: OR = 2.35; with relatives: OR = 3.09), aberrant motor behaviour (with staff: OR = 2.02), and elation (with relatives: OR = 10.55). CONCLUSIONS: Neuropsychiatric symptoms and CR are common among RF residents and are reciprocally associated. Further research with longitudinal design is needed to better understand this relationship. PMID- 26817665 TI - Molecular and comparative morphological analysis of central European parasitic flatworms of the superfamily Brachylaimoidea Allison, 1943 (Trematoda: Plagiorchiida). AB - The Brachylaimoidea are digenean parasites of vertebrates, including humans, domestic animals, poultry and wild game. Numerous Brachylaimoidea, particularly adults of Brachylaima and Leucochloridium, are difficult to identify to species. We provide and analyse sequences of two nuclear (18S rDNA, ITS2) and two mitochondrial (CO1, ND1) DNA loci of central European species of the Brachylaimoidea, namely Leucochloridium holostomum, Leucochloridium paradoxum, Leucochloridium perturbatum, Leucochloridium subtilis, Leucochloridium vogtianum, Urotocus rossitensis, Urogonimus macrostomus, Michajlovia migrata, Leucochloridiomorpha lutea, Brachylaima arcuatus, Brachylaima fuscata and Brachylaima mesostoma. We identified three clades in the genus Leucochloridium, which do not correspond to the previously suggested subgenera Neoleucochloridium, Papilloleucochloridium and Leucochloridium. We reject classification of Urotocus and Urogonimus in Leucochloridiinae, and, instead, re-establish the subfamilies Urotocinae and Urogoniminae. We synonymize the genus Renylaima with the genus Brachylaima. We reject M. migrata as a member of Leucochloridiinae sensu stricto or Brachylaimidae suggested by some previous authors. We found that the previously sequenced Glaphyrostomum sp. does not cluster with any hitherto sequenced Brachylaimidae. We also provide comparative measurements of the examined central European Brachylaimoidea, address the the specificity of their localization in the host and discuss their host-specific prevalence and intensity of infections based on the extensive dataset of birds examined in 1962-2015. PMID- 26817666 TI - The Schizophrenia Polygenic Risk Score: To What Does It Predispose in Adolescence? PMID- 26817667 TI - Heterozygosity for a Novel Missense Mutation in the ITGB4 Gene Associated With Autosomal Dominant Epidermolysis Bullosa. AB - IMPORTANCE: Epidermolysis bullosa (EB) is a group of mechanobullous genodermatoses characterized by the fragility of skin and mucous membranes. Mutations in the ITGA6 and ITGB4 genes, encoding the hemidesmosomal protein alpha6beta4-integrin, have been involved in the pathogenesis of EB. To date, the inheritance of these particular genes is known to be exclusively autosomal recessive. Herein, we report a novel heterozygous missense mutation in the ITGB4 gene exerting a dominant negative effect that cosegregates with the EB phenotype in an extended family. OBSERVATIONS: The clinical phenotype of affected individuals is primarily characterized by nail dystrophy and late onset of mild skin fragility and acral blistering. Some patients developed granulation tissue in the larynx, urethra, lacrimal duct, and external auditory canal. Sequencing the complete set of genes associated with EB revealed a heterozygous missense mutation in exon 5 of ITGB4: c.433G>T, p.Asp145Tyr. The mutation was found in the affected relatives and was not present in unaffected relatives and control DNA samples. CONCLUSIONS AND RELEVANCE: This study highlights, for the first time to our knowledge, the possibility of a dominant mode of inheritance for a missense ITGB4 mutation in EB, thus expanding the mutational database and genotype phenotype correlation for this rare disease. PMID- 26817668 TI - Tailoring unidirectional angular radiation through multipolar interference in a single-element subwavelength all-dielectric stair-like nanoantenna. AB - The study of all-dielectric nanoantennas has become an emerging branch of the study of optical nanoantennas in recent years, with all-dielectric nanoantennas having an outstanding ability to tailor forward and backward unidirectional scattering arising from interference mainly between electric dipoles and magnetic dipoles induced simultaneously inside a nanoparticle. To further control their radiation properties, we demonstrate the off-normal scattering, by a silicon stair-like nanoantenna, of an incident near-infrared plane wave due to multipolar interference. The radiation angle could be tailored over a 20-degree range by tuning the geometric parameters of the nanoantenna. A multipolar model was adopted to interpret the interference among one electric dipole, two magnetic dipoles and one electric quadrupole induced inside the nanoantenna. The maximum radiation angle reached 20 degrees at a wavelength near 1550 nm. Such a stair like nanoantenna sets a good example for further flexible manipulation of multipolar resonances inside all-dielectric nanoparticles, which is an essential step towards practical application of all-dielectric nanoantennas in the near future. PMID- 26817669 TI - Routine whole body CT of high energy trauma patients leads to excessive radiation exposure. AB - BACKGROUND: Whole body computed tomography (WBCT) is an important adjunct in trauma care, which is often part of standard protocol in initial management of trauma patients. However, WBCT exposes patients to a significant dose of radiation. The use of WBCT was assessed in a modern trauma cohort in Sweden. METHODS: A two-center retrospective cohort study was performed. All consecutive trauma alert patients at a university hospital (July-December 2008), and a rural county hospital (January 2009- December 2010) were included. Patients were stratified into three groups (high, intermediate and low risk) based on documented suspected injuries at primary survey at the site of accident or at the emergency department. Injury severity score (ISS) was calculated. Case records were reviewed for clinical and radiological findings at the time of trauma, and during a >=36 months of follow-up period to identify possible missed injuries. RESULTS: A total of 523 patients were included in the study (university hospital n = 273; rural county hospital n = 250), out of which 475 patients (91.0 %) underwent radiological examinations, 290 patients (55.4 %) underwent WBCT, which identified trauma related findings in 125 patients (43.1 % of those examined). The high-risk group (n = 62) had a mean age of 38.5 years (21.1 SD). Mean ISS was 16.48 (18.14 SD). In this group, WBCT resulted in a positive finding in 38 (74.5 %) patients. In the intermediate-risk group (n = 322; mean age 37.66, 20.24 SD) ISS was 4.42 (6.30 SD). A positive finding on WBCT was found in 87 of the intermediate group patients (44.8 %). The low-risk group (n = 139; mean age 32.5 years; 21.4 SD) had a mean ISS of 0.84 (1.57 SD) with no positive findings on WBCT and no missed injuries in medical records at >=36 months. DISCUSSION: The risk of developing radiation induced cancer is significant for young people if exposed to relatively high dose radiation as is the case in WBCT. WBCT in high energy trauma is important for planning of treatment in severely injured patients while it can be questioned in the seemingly not injured where it is used mainly to permit early discharge from the ED. CONCLUSIONS: Risk stratification criteria could in this retrospective study identify high energy trauma patients not in need of radiological imaging. WBCT in high-energy trauma does not affect patient care if the patient is mentally alert, not intoxicated nor shows signs of other than minor injuries when evaluated by a trauma-team. The risk of missing important traumatic findings in these patients is very low. Observation of the patient with reexamination instead of imaging may be considered in this group of often young patients where radiation dose is an issue. PMID- 26817671 TI - [Chilaiditi's sign]. PMID- 26817670 TI - Oscillating behavior of Clostridium difficile Min proteins in Bacillus subtilis. AB - In rod-shaped bacteria, the proper placement of the division septum at the midcell relies, at least partially, on the proteins of the Min system as an inhibitor of cell division. The main principle of Min system function involves the formation of an inhibitor gradient along the cell axis; however, the establishment of this gradient differs between two well-studied gram-negative and gram-positive bacteria. While in gram-negative Escherichia coli, the Min system undergoes pole-to-pole oscillation, in gram-positive Bacillus subtilis, proper spatial inhibition is achieved by the preferential attraction of the Min proteins to the cell poles. Nevertheless, when E.coli Min proteins are inserted into B.subtilis cells, they still oscillate, which negatively affects asymmetric septation during sporulation in this organism. Interestingly, homologs of both Min systems were found to be present in various combinations in the genomes of anaerobic and endospore-forming Clostridia, including the pathogenic Clostridium difficile. Here, we have investigated the localization and behavior of C.difficile Min protein homologs and showed that MinDE proteins of C.difficile can oscillate when expressed together in B.subtilis cells. We have also investigated the effects of this oscillation on B.subtilis sporulation, and observed decreased sporulation efficiency in strains harboring the MinDE genes. Additionally, we have evaluated the effects of C.difficile Min protein expression on vegetative division in this heterologous host. PMID- 26817672 TI - [Emphysematous cystitis]. PMID- 26817673 TI - Efficacy and tolerability of different brands of intravenous immunoglobulin in the maintenance treatment of chronic immune-mediated neuropathies. AB - High-dose intravenous immunoglobulin (IVIg) is effective in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Not all brands of IVIg are however licensed for these neuropathies. We reviewed six patients with CIDP and seven with MMN treated with maintenance therapy with IVIg from 2009 to 2013. In all patients, we measured the Medical Research Council (MRC) and Overall Neuropathy Limitation Scale (ONLS) scores before each infusion, registered the monthly dose and brand of IVIg, and recorded adverse events. Patients were treated for 25-60 months (mean 49 months) alternating different brands of IVIg including IgVena, Gammagard, Kiovig, and Flebogamma. Minor and transient side effects were equally observed with each brand. No difference in the MRC or ONLS scores was observed in relation to the brand of IVIg used. Chronic maintenance treatment with IVIg in patients with MMN and CIDP was not associated with a different tolerability or efficacy despite the use of different brands of IVIg. PMID- 26817674 TI - Multiphoton photochemical crosslinking-based fabrication of protein micropatterns with controllable mechanical properties for single cell traction force measurements. AB - Engineering 3D microstructures with predetermined properties is critical for stem cell niche studies. We have developed a multiphoton femtosecond laser-based 3D printing platform, which generates complex protein microstructures in minutes. Here, we used the platform to test a series of fabrication and reagent parameters in precisely controlling the mechanical properties of protein micropillars. Atomic force microscopy was utilized to measure the reduced elastic modulus of the micropillars, and transmission electron microscopy was used to visualize the porosity of the structures. The reduced elastic modulus of the micropillars associated positively and linearly with the scanning power. On the other hand, the porosity and pore size of the micropillars associated inversely and linearly with the scanning power and reagent concentrations. While keeping the elastic modulus constant, the stiffness of the micropillars was controlled by varying their height. Subsequently, the single cell traction forces of rabbit chondrocytes, human dermal fibroblasts, human mesenchymal stem cells, and bovine nucleus pulposus cells (bNPCs) were successfully measured by culturing the cells on micropillar arrays of different stiffness. Our results showed that the traction forces of all groups showed positive relationship with stiffness, and that the chondrocytes and bNPCs generated the highest and lowest traction forces, respectively. PMID- 26817675 TI - Examining driver behavior at the onset of yellow in a traffic simulator environment: Comparisons between random parameters and latent class logit models. AB - This study involves an examination of driver behavior at the onset of a yellow signal indication. Behavioral data were obtained from a driving simulator study that was conducted through the National Advanced Driving Simulator (NADS) laboratory at the University of Iowa. These data were drawn from a series of events during which study participants drove through a series of intersections where the traffic signals changed from the green to yellow phase. The resulting dataset provides potential insights into how driver behavior is affected by distracted driving through an experimental design that alternated handheld, headset, and hands-free cell phone use with "normal" baseline driving events. The results of the study show that male drivers ages 18-45 were more likely to stop. Participants were also more likely to stop as they became more familiar with the simulator environment. Cell phone use was found to some influence on driver behavior in this setting, though the effects varied significantly across individuals. The study also demonstrates two methodological approaches for dealing with unobserved heterogeneity across drivers. These include random parameters and latent class logit models, each of which analyze the data as a panel. The results show each method to provide significantly better fit than a pooled, fixed parameter model. Differences in terms of the context of these two approaches are discussed, providing important insights as to the differences between these modeling frameworks. PMID- 26817676 TI - [Is vitamin D supplementation effective for the prevention of falls in elderly people?]. AB - Falls in elderly people are common and come with important effects on morbidity and mortality, dependence and institutionalization. It has been proposed that supplementation of vitamin D could prevent the occurrence of this event. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified 18 systematic reviews including 31 randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded the use of vitamin D probably leads to little or no difference in the risk of falling in elderly people. PMID- 26817677 TI - Ganoderma lucidum total triterpenes prevent gamma-radiation induced oxidative stress in Swiss albino mice in vivo. AB - OBJECTIVES: The in vivo radio-protective effect of total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst was evaluated using Swiss albino mice, by pre-treatment with total triterpenes for 14 days, followed by a whole body exposure to gamma-radiation. METHODS: The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and the level of reduced glutathione (GSH) were analysed in liver and brain homogenates. The extent of lipid and protein peroxidation was also estimated in liver and brain homogenates after irradiation. Protection of radiation-induced DNA strand breaks in peripheral blood lymphocytes and bone marrow cells was assessed using the comet assay. RESULTS: Total triterpenes were highly effective in reducing the levels of lipid peroxidation and protein oxidation to near normal values in both liver and brain tissues. Total triterpenes, when administered in vivo, were also found to be successful in restoring the antioxidant enzyme activities and GSH level in liver and brain of irradiated mice. Administration of total triterpenes, prior to radiation exposure, significantly decreased the DNA strand breaks. DISCUSSION: The results of the present study thus revealed the potential therapeutic use of Ganoderma total triterpenes as an adjuvant in radiation therapy. PMID- 26817679 TI - Ternary rare earth silicides RE2M3Si4 (RE = Sc, Y, Lu; M = Mo, W): crystal structure, coloring and electronic properties. AB - The ternary compounds Sc2Mo3Si4, Y2Mo3Si4, Lu2Mo3Si4 and Sc2W3Si4 have been synthesized using arc melting and structurally characterized using single crystal X-ray diffraction. The compounds are isostructural with Gd5Si4 but with coloring (order of the rare earth and transition metals) on the Gd site. In contrast to group 4 and 5 ternaries of the same type, we observe no site mixing between the rare earth and transition metals. The Y compound displays a different, less common coloring from the others and through DFT calculations and investigation of the solid solution between Sc2Mo3Si4 and Y2Mo3Si4 it is shown that the different coloring of the latter is only marginally more stable. The electronic structures of the ternary compounds have been investigated using DFT calculations, yielding densities of states very similar to Gd5Si4. These predict metallic behavior and no magnetism, which is confirmed through resistivity and magnetization measurements. PMID- 26817678 TI - Calmodulin disruption impacts growth and motility in juvenile liver fluke. AB - BACKGROUND: Deficiencies in effective flukicide options and growing issues with drug resistance make current strategies for liver fluke control unsustainable, thereby promoting the need to identify and validate new control targets in Fasciola spp. parasites. Calmodulins (CaMs) are small calcium-sensing proteins with ubiquitous expression in all eukaryotic organisms and generally use fluctuations in intracellular calcium levels to modulate cell signalling events. CaMs are essential for fundamental processes including the phosphorylation of protein kinases, gene transcription, calcium transport and smooth muscle contraction. In the blood fluke Schistosoma mansoni, calmodulins have been implicated in egg hatching, miracidial transformation and larval development. Previously, CaMs have been identified amongst liver fluke excretory-secretory products and three CaM-like proteins have been characterised biochemically from adult Fasciola hepatica, although their functions remain unknown. METHODS: In this study, we set out to investigate the biological function and control target potential of F. hepatica CaMs (FhCaMs) using RNAi methodology alongside novel in vitro bioassays. RESULTS: Our results reveal that: (i) FhCaMs are widely expressed in parenchymal cells throughout the forebody region of juvenile fluke; (ii) significant transcriptional knockdown of FhCaM1-3 was inducible by exposure to either long (~200 nt) double stranded (ds) RNAs or 27 nt short interfering (si) RNAs, although siRNAs were less effective than long dsRNAs; (iii) transient long dsRNA exposure-induced RNA interference (RNAi) of FhCaMs triggered transcript knockdown that persisted for >= 21 days, and led to detectable suppression of FhCaM proteins; (iv) FhCaM RNAi significantly reduced the growth of juvenile flukes maintained in vitro; (v) FhCaM RNAi juveniles also displayed hyperactivity encompassing significantly increased migration; (vi) both the reduced growth and increased motility phenotypes were recapitulated in juvenile fluke using the CaM inhibitor trifluoperazine hydrochloride, supporting phenotype specificity. CONCLUSIONS: These data indicate that the Ca(2+)-modulating functions of FhCaMs are important for juvenile fluke growth and movement and provide the first functional genomics-based example of a growth-defect resulting from gene silencing in liver fluke. Whilst the phenotypic impacts of FhCaM silencing on fluke behaviour do not strongly support their candidature as new flukicide targets, the growth impacts encourage further consideration, especially in light of the speed of juvenile fluke growth in vivo. PMID- 26817680 TI - Carbon-Impurity Affected Depth Elemental Distribution in Solution-Processed Inorganic Thin Films for Solar Cell Application. AB - A common feature of the inorganic thin films including Cu(In,Ga)(S,Se)2 fabricated by nonvacuum solution-based approaches is the doubled-layered structure, with a top dense inorganic film and a bottom carbon-containing residual layer. Although the latter has been considered to be the main efficiency limiting factor, (as a source of high series resistance), the exact influence of this layer is still not clear, and contradictory views are present. In this study, using a CISe as a model system, we report experimental evidence indicating that the carbon residual layer itself is electrically benign to the device performance. Conversely, carbon was found to play a significant role in determining the depth elemental distribution of final film, in which carbon selectively hinders the diffusion of Cu during selenization, resulting in significantly Cu-deficient top CISe layer while improving the film morphology. This carbon-affected compositional and morphological impact on the top CISe films is a determining factor for the device efficiency, which was supported by the finding that CISe solar cells processed from the precursor film containing intermediate amount of carbon demonstrated high efficiencies of up to 9.15% whereas the performances of the devices prepared from the precursor films with very high and very low carbon were notably poor. PMID- 26817681 TI - The role of separate margins sampling in endoscopic laser surgery for early glottic cancer. AB - CONCLUSIONS: Sampling surgical margins in trans-oral laser microsurgery for early glottic squamous cell carcinoma (SCC) may allow for increased local control rate, although with no difference in local control by endoscopic treatment alone. OBJECTIVE: To further delineate the role of routinely sampling separate surgical margins, in patients with early glottic SCC undergoing endoscopic laser resection. METHODS: A retrospective case control study. One hundres and two early glottic cancer patients staged Tis-T2 underwent endoscopic laser surgery with curative intent as the primary treatment. Separate margins from the surgical bed were sampled following complete tumor resection in 64 patients; in 38 patients no margins were sampled. RESULTS: Margin sampling showed a tendency towards reduced risk for local recurrence, adjusted HR = 0.439 (p-value = 0.096). However, there was no difference in local control by endoscopic treatment alone. The patients with sampled margins were further divided based on margins' status: 39 (61%) had negative margins, and 25 (39%) had positive margins. Compared with negative margins, patients with positive margins showed increased risk for recurrence, adjusted HR = 8.492 (p = 0.008). When margins were not sampled the risk for local recurrence was increased compared to negative margins (adjusted HR = 7.875, p value = 0.008), and relatively comparable to what was observed when sampled margins were positive (adjusted HR = 0.927, p-value = 0.88). PMID- 26817682 TI - Chemically Engraving Semiconductor Nanowires: Using Three-Dimensional Nanoscale Morphology to Encode Functionality from the Bottom Up. AB - The patterning of semiconductors with nanometer-scale precision is a cornerstone of modern technology. Top-down methods, ranging from photolithography to focused ion beam milling, are typically used to fabricate complex nanostructures. In this Perspective, we discuss an alternative bottom-up method to encode similar high resolution morphology in semiconductor nanowires (NWs). This process, termed ENGRAVE for "Encoded Nanowire GRowth and Appearance through VLS and Etching", combines fast modulation of nanowire composition during vapor-liquid-solid (VLS) growth with composition-dependent wet-chemical etching. This method produces cylindrically symmetric structures in which the diameter is modulated on a sub-10 nm axial length scale. The process can produce patterns that range from periodic, centrosymmetric to nonperiodic, asymmetric structures, including gratings, fractals, tapers, ratchets, sinusoids, nanogaps, and nanodots. We discuss the prospect for the ENGRAVE process to become a complementary method of lithographic like patterning that encodes unique morphologies and physical properties in semiconductors for a range of technologies. PMID- 26817684 TI - Cytotoxic and apoptotic effects of heat killed Mycobacterium indicus pranii (MIP) on various human cancer cell lines. AB - Mycobacterium indicus pranii (MIP) is a non-pathogenic mycobacterium, which has been tested on several cancer types like lung and bladder where tumour regression and complete recovery was observed. In discovering the potential cytotoxic elements, a preliminary test was carried out using four different fractions consisting of live bacteria, culture supernatant, heat killed bacteria and heat killed culture supernatant of MIP against two human cancer cells A549 and CaSki by 3-(4,5-dimethyl thiazol)-2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptosis was investigated in MCF-7 and ORL-115 cancer cells by poly-(ADP-ribose) polymerase (PARP) and DNA fragmentation assays. Among four MIP fractions, only heat killed MIP fraction (HKB) showed significant cytotoxicity in various cancer cells with inhibitory concentration, IC50 in the range 5.6-35.0 MUl/(1.0 * 10(6) MIP cells/ml), while cytotoxicity effects were not observed in the remaining fractions. HKB did not show cytotoxic effects on non-cancerous cells contrary to cancerous cells, suggesting its safe usage and ability to differentially recognize between these cells. Evaluation on PARP assay further suggested that cytotoxicity in cancer cells were potentially induced via caspase-mediated apoptosis. The cytotoxic and apoptotic effects of MIP HKB have indicated that this fraction can be a good candidate to further identify effective anti-cancer agents. PMID- 26817685 TI - Two Novel Psychomotor Tasks in Idiopathic Normal Pressure Hydrocephalus. AB - OBJECTIVE: Idiopathic normal pressure hydrocephalus (INPH) is a neurological disorder presenting with gait, cognitive, and bladder symptoms in the context of ventricular enlargement. Although gait is the primary indicator for treatment candidacy and outcome, additional monitoring tools are needed. Line Tracing Test (LTT) and Serial Dotting Test (SDT), two psychomotor tasks, have been introduced as potential outcome measures but have not been widely studied. This preliminary study examined whether LTT and SDT are sensitive to motor dysfunction in INPH and determined if accuracy and time are important aspects of performance. METHODS: Eighty-four INPH subjects and 36 healthy older adults were administered LTT and SDT. Novel error scoring procedures were developed to make scoring practical and efficient; interclass correlation showed good reliability of scoring procedures for both tasks (0.997; p<.001). RESULTS: The INPH group demonstrated slower performance on SDT (p<.001) and made a greater number of errors on both tasks (p<.001). Combined Time/Error scores revealed poorer performance in the INPH group for original-LTT (p<.001), modified-LTT (p <= .001) and SDT (p<.001). CONCLUSIONS: These findings indicate LTT and SDT may prove useful for monitoring psychomotor skills in INPH. While completion time reflects impaired processing speed, reduced accuracy may suggest planning and self-monitoring difficulties, aspects of executive functioning known to be compromised in INPH. This is the first study to underscore the importance of performance accuracy in INPH and introduce practical/reliable error scoring for these tasks. Future work will establish reliability and validity of these measures and determine their utility as outcome tools. PMID- 26817686 TI - Emerging amyloid disease-modifying drugs for Alzheimer's disease. PMID- 26817687 TI - Declining trends in the rates of assisted injecting: a prospective cohort study. AB - BACKGROUND: Assisted injecting has been associated with increased risk of blood borne infections, overdose, and other harms among people who inject drugs (PWID), particularly women. Given the changing availability of relevant harm reduction interventions in Vancouver, Canada, in recent years, we conducted a gender-based analysis to examine changes in rates and correlates of assisted injecting over time among active PWID. METHODS: Using data from a prospective cohort of PWID in Vancouver, we employed gender-stratified multivariable generalized estimating equations to examine trends in assisted injecting and identify the correlates during two periods: June 2006-November 2009 and December 2009-May 2014. RESULTS: Among 1119 participants, 376 (33.6 %) were females. Rates of assisted injecting declined between 2006 and 2014 among males (21.9 to 13.8%) and females (37.0 to 25.6%). In multivariable analyses, calendar year of interview also remained independently and negatively associated with assisted injecting among males (adjusted odds ratio [AOR] 0.95, 95% confidence interval [CI] 0.92-0.99) and females (AOR 0.93, 95% CI 0.89-0.97). Syringe borrowing remained independently associated with assisted injecting throughout the study period among females (AOR 1.53, 95% CI 1.10-2.11 during 2006-2009; AOR 2.15, 95% CI 1.24-3.74 during 2009 2014) and during 2009-2014 among males (AOR 1.88, 95% CI 1.02-3.48). CONCLUSIONS: Our findings demonstrate assisted injecting has significantly decreased for both males and females over the past decade. Nevertheless, rates of assisted injecting remain high, especially among women, and are associated with high-risk behavior, indicating a need to provide safer assisted injecting services to these vulnerable sub-populations of PWID. PMID- 26817688 TI - A rare case of gangrene of cystic duct due to the insertion of endoscopic nasobiliary drainage (ENBD) tube into the cystic duct by mistake. AB - This is the first case report of Gangrenous cholecystitis due to the insertion of endoscopic nasobiliary drainage (ENBD) tube into the cystic duct by mistake,The reason why it happened may be related to Inflammation and hypoimmunity. PMID- 26817689 TI - Characterization of HAF-4- and HAF-9-localizing organelles as distinct organelles in Caenorhabditis elegans intestinal cells. AB - BACKGROUND: The intestinal cells of Caenorhabditis elegans are filled with heterogeneous granular organelles that are associated with specific organ functions. The best studied of these organelles are lipid droplets and acidified gut granules associated with GLO-1, a homolog of the small GTPase Rab38. In this study, we characterized a subset of the intestinal granules in which HAF-4 and HAF-9 localize on the membrane. HAF-4 and HAF-9 are ATP-binding cassette (ABC) transporter proteins that are homologous to the mammalian lysosomal peptide transporter TAPL (transporter associated with antigen processing-like, ABCB9). RESULTS: Using transgenic worms expressing fluorescent protein-tagged marker proteins, we demonstrated that the HAF-4- and HAF-9-localizing organelles are not lipid droplets and do not participate in yolk protein transport. They were also ruled out as GLO-1-positive acidified gut granules. Furthermore, we clarified that the late endosomal protein RAB-7 localizes to the HAF-4- and HAF-9 localizing organelles and is required for their biogenesis. CONCLUSIONS: Our results indicate that the HAF-4- and HAF-9-localizing organelles are distinct intestinal organelles associated with the endocytic pathway. PMID- 26817690 TI - Meibomian gland dysfunction: hyperkeratinization or atrophy? AB - Meibomian gland dysfunction (MGD) is the major cause of evaporative dry eye disease (EDED) and dysfunction is widely thought to mechanistically involve ductal hyperkeratinization, plugging and obstruction. This review re-evaluates the role of hyperkeratinization in MGD based on more recent findings from mouse models. In these studies, eyelids from normal young and old mice or mice exposed to desiccating stress were evaluated by immunofluorescent tomography and 3 dimensional reconstruction to evaluate gland volume, expression of hyperkeratinization markers and cell proliferation or stimulated Raman scattering (SRS) microscopy to assess lipid quality. Results indicate that aging mice show dropout of meibomian glands with loss of gland volume and a forward migration of the mucocutaneous junction anterior to the gland orifice; similar age-related changes that are detected in human subjects. Atrophic glands also showed evidence of epithelial plugging of the orifice without the presence of hyperkeratinization. Mice exposed to desiccating stress showed hyperproliferation of the meibomian gland and ductal dilation suggesting a marked increase in lipid synthesis. Lipid quality was also affected in EDED mice with an increase in the protein content of lipid within the duct of the gland. Overall, age-related changes in the mouse show similar structural and functional correlates with that observed in clinical MGD without evidence of hyperkeratinization suggesting that gland atrophy may be a major cause of EDED. The response of the meibomian gland to desiccating stress also suggest that environmental conditions may accelerate or potentiate age-related changes. PMID- 26817691 TI - Early cardiovascular events in women with a history of gestational diabetes mellitus. AB - BACKGROUND: The effect of gestational diabetes mellitus (GDM) on cardiovascular diseases (CVD) is not assessed within the first 10 years postpartum, regardless of subsequent diabetes. The aim of this study was to determine the risk of CVD events related to GDM within 7 years of postpartum. METHODS: This nationwide population-based study of deliveries in 2007 and 2008 with a follow-up of 7 years was based on data from the French medico-administrative database. Two groups were formed: women with a history of GDM and women without GDM or previous diabetes. CVD included angina pectoris, myocardial infarction, stroke, heart bypass surgery, coronary angioplasty, carotid endarterectomy and fibrinolysis. Hypertensive disease was assessed separately. Determinants studied included age, obesity, subsequent diabetes mellitus and hypertensive diseases during pregnancy. Adjusted odds ratios for outcomes were calculated using multiple logistic regressions. RESULTS: The hospital database recorded 1,518,990 deliveries in 2007 and 2008. Among these, 62,958 women had a history of GDM. After adjusting for age, DM, obesity and hypertensive disorders in pregnancy, GDM was significantly associated with a higher risk of CVD (adjusted Odds Ratio aOR = 1.25 [1.09 1.43]). Considering each variable in a separate model, GDM was associated with angina pectoris (aOR = 1.68 [1.29-2.20]), myocardial infarction (aOR = 1.92 [1.36 2.71]) and hypertension (aOR = 2.72 [2.58-2.88]) but not with stroke. CONCLUSIONS: A history of GDM was identified as a risk factor of CVD, especially coronary vascular diseases, within the 7 years postpartum. A lifestyle changes from postpartum onwards can be recommended and supported. PMID- 26817692 TI - Distribution of genital human papillomavirus genotypes in benign clinical manifestations among men from Northern Spain. AB - BACKGROUND: In the literature, data on the prevalence of human papillomavirus (HPV) infection in men vary significantly and the exact distribution of specific genotypes is still unclear. As infections usually occur without symptoms, men might only attend their hospital clinic when they have a specific concern, being in most cases genital warts (condylomas), which are often caused by low-risk HPV genotypes. The aim of this study was to assess HPV genotype distribution and prevalence among men attending hospital for HPV-associated conditions and to evaluate infection-associated factors. METHODS: Samples from men with clinical manifestations of HPV-related infections seen during 2007-2012 at the Clinical Microbiology and Infectious Control Department at Basurto University Hospital were genotyped using Linear Array HPV Genotyping Test kit (Roche Molecular Diagnostics, Germany). Data on probable risk factors were collected and investigated for possible association. RESULTS: Of 184 anogenital samples, 138 (75 %) were tested as positive for HPV; 57 (41.3 %) single HPV infections and 81 (58.7 %) multiple infections. Only 45.6 % of HPV-positive samples presented low risk genotypes 6 or 11, whereas 71/138 (51.4 %) had at least one oncogenic (high risk) genotype. Oncogenic genotypes and multiple HPV infections were both associated with a higher number of lifetime sexual partners and their incidence appeared to increase with patient age. CONCLUSIONS: Although it is accepted that HPV 6 and 11 genotypes are main causes of condylomas, our findings show a high incidence of multiple infections and high-risk genotypes in men with benign HPV manifestations. The fact that the condyloma is a skin lesion facilitates the entry of virus into cells and thus cancer progression; therefore, monitoring for HPV is important, especially in those patients with high-risk genotypes (regardless of whether they cause condyloma). PMID- 26817693 TI - Developing doctors: what are the attitudes and perceptions of year 1 and 2 medical students towards a new integrated formative objective structured clinical examination? AB - BACKGROUND: Objective Structured Clinical Examination (OSCE) is a core component of undergraduate medical student assessment. With increased emphasis on integrated programmes, more courses include OSCEs in the traditionally 'preclinical' years. The acceptability and impact of such assessment methods at this stage of training is unknown. METHODS: In 2013 and 2014 University College London Medical School piloted a formative, integrated OSCE in years 1 and 2 of the undergraduate medical degree programme. This study with a sequential exploratory design aimed to explore the acceptability and impact of such an OSCE in the early years of medical school. 1280 students completed the OSCE and were invited to complete a questionnaire exploring their views of the OSCE (response rate 96.6%). Four focus groups, each with five or six participants (22 in total) were subsequently held to further explore themes. Data was independently transcribed and coded using thematic analysis. RESULTS: Students were strongly in favour of the introduction of an OSCE in addition to existing assessments. Six overarching themes were identified: application of knowledge and skills; OSCE as an experience; OSCE as a process; a learning curve; becoming a doctor; and creating an effective OSCE. CONCLUSIONS: Results strongly support the role of OSCE early in the medical course with many benefits reported. An OSCE at this stage aligns with the vision of integrated medical education which includes early patient contact and introduction of clinical and professional skills. It also fosters feelings of responsibility and professional identity amongst students. PMID- 26817695 TI - Increased oxidative stress from early pregnancy in women who develop preeclampsia. AB - Preeclampsia (PE) is a pregnancy-specific disorder, defined as new onset of maternal hypertension and proteinuria after 20 weeks of gestation. Our earlier study has shown increased maternal oxidative stress at delivery to be associated with poor birth outcome in PE. However, these results were observed when the pathology had progressed and may have been secondary to the effects of the disorder. To understand the role of antioxidant defense mechanisms in PE right from early pregnancy, in this prospective study, we measured malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH) concentrations in maternal blood at 3 time-points of gestation [16-20 weeks (T1), 26-30 weeks (T2), at delivery (T3)] and in cord blood. Gene expression of SOD and GPx and protein levels of endothelial nitric oxide synthase (eNOS) enzyme were also analyzed in the placenta. MDA levels were higher at T1 (p < 0.01) and T2 (p < 0.01) in women with PE as compared with control. GPx levels were higher at T3 (p < 0.05) while SOD levels were lower at T2 (p < 0.05), T3 (p < 0.01) and in cord (p < 0.01) in PE. GSH levels at T1 (p < 0.05) and expression of GPx in the placenta were lower in PE as compared with control. In conclusion, this study demonstrates that women who develop PE exhibit increased oxidative stress right from 16 to 20 weeks of gestation. This may alter placental development and lead to fetal programming of adult non-communicable disease in the offspring. PMID- 26817697 TI - Toxicological study of the butanol fractionated root extract of Asparagus africanus Lam., on some blood parameter and histopathology of liver and kidney in mice. AB - BACKGROUND: The butanol fractionated root extract of Asparagus africanus Lam., a traditional herb widely used to treat various ailments were analyzed for the presence of potential toxicity after single (acute) and repeated (subchronic) dose oral administration in adult swiss albino mice using gavages. METHODS: For the acute study, butanol fractionated extract of the plant was administered in single doses of 1000, 3000 and 5000 mg/kg body weight. In the sub-chronic dose study, the extract was administered at doses of 300 and 600 mg/kg body weight/day for 42 days. Selected hematological and biochemical parameters of the blood followed by histopathological analysis were investigated after 42 days of daily administrations. The results were expressed as M +/- SE, and differences at P < 0.05 was considered significant. One way analysis of variance (ANOVA) and least significant difference tests were employed to check the significant differences between the various parameters of the experimental groups. RESULTS: In the acute study, the extract did not caused dose-dependent general behavioral adverse effects, body weight change and mortality. The single dose toxicity studies therefore showed that the butanol fraction of the extract has high safety profile when given orally. After 42 days of daily dosing, in the sub-chronic study, no clinically significant changes were observed for hematological and biochemical parameters. Except an occasional small number of focal mononuclear lymphocytic cells infiltrations around the central and portal triad of the liver of a few mice, the histopathological parameters do not show significant change. CONCLUSION: It is concluded that, the butanol fractionated extract from A. africanus at the given dose does not show significant toxicity. The presence of focal inflammation on the liver of a few mice may be associated to the presence of flavonoid glycoside in the butanol fractionated extract. PMID- 26817698 TI - HLA-DQB1 gene polymorphisms and non-segmental vitiligo: A case-control study in the Korean population. PMID- 26817696 TI - Mixed-strain housing for female C57BL/6, DBA/2, and BALB/c mice: validating a split-plot design that promotes refinement and reduction. AB - BACKGROUND: Inefficient experimental designs are common in animal-based biomedical research, wasting resources and potentially leading to unreplicable results. Here we illustrate the intrinsic statistical power of split-plot designs, wherein three or more sub-units (e.g. individual subjects) differing in a variable of interest (e.g. genotype) share an experimental unit (e.g. a cage or litter) to which a treatment is applied (e.g. a drug, diet, or cage manipulation). We also empirically validate one example of such a design, mixing different mouse strains -- C57BL/6, DBA/2, and BALB/c -- within cages varying in degree of enrichment. As well as boosting statistical power, no other manipulations are needed for individual identification if co-housed strains are differentially pigmented, so also sparing mice from stressful marking procedures. METHODS: The validation involved housing 240 females from weaning to 5 months of age in single- or mixed- strain trios, in cages allocated to enriched or standard treatments. Mice were screened for a range of 26 commonly-measured behavioural, physiological and haematological variables. RESULTS: Living in mixed-strain trios did not compromise mouse welfare (assessed via corticosterone metabolite output, stereotypic behaviour, signs of aggression, and other variables). It also did not alter the direction or magnitude of any strain- or enrichment-typical difference across the 26 measured variables, or increase variance in the data: indeed variance was significantly decreased by mixed- strain housing. Furthermore, using Monte Carlo simulations to quantify the statistical power benefits of this approach over a conventional design demonstrated that for our effect sizes, the split- plot design would require significantly fewer mice (under half in most cases) to achieve a power of 80%. CONCLUSIONS: Mixed-strain housing allows several strains to be tested at once, and potentially refines traditional marking practices for research mice. Furthermore, it dramatically illustrates the enhanced statistical power of split-plot designs, allowing many fewer animals to be used. More powerful designs can also increase the chances of replicable findings, and increase the ability of small-scale studies to yield significant results. Using mixed-strain housing for female C57BL/6, DBA/2 and BALB/c mice is therefore an effective, efficient way to promote both refinement and the reduction of animal-use in research. PMID- 26817699 TI - Kinin receptors in skin wound healing. AB - BACKGROUND: Wound healing is a complex and dynamic process that includes 3 different phases: inflammation, proliferation, and remodeling. Kinins are vasoactive peptides released after tissue injury, and are directly involved in the development and maintenance of inflammatory processes, and their actions are mediated by the activation of receptors called B1 and B2. OBJECTIVE: We aimed to evaluate the involvement of kinin receptors in the skin healing process. METHODS: Knockout mice for kinin receptors (KOB1, KOB2 and KOB1B2) and wild type controls (WT) were subjected to a skin excision model, and tissue repair process was evaluated during different phases of wound healing. RESULTS: In knockout animals for kinin receptors differences were observed in the resolution period of injury exceeding 17 days for the total closure of wounds. The absence of kinin receptors promotes a significant reduction in infiltration of polymorphonuclear cells on day 2 of the inflammatory phase. Already at the late stage of this phase (3 days) there was a negative influence on the infiltration of polymorphonuclear and mononuclear cells at the site of injury in comparison to WT. Collagen was significantly diminished in tissue of KOB1, KOB2 and KOB1B2 from day two to the end of the healing process. Moreover, wound tissue from KOB2 and KOB1B2, but not KOB1, presented impaired parameters of re-epitheliazation, reduced proliferation of cells (PCNA immunostaining), and a lower number of myofibroblasts (alpha-SMA immunostaining). CONCLUSION: These data reveal the involvement of kinin receptors in processes of skin repair. Both kinin receptors participate especially during the inflammatory phase, while B2 receptors seem to be more relevant in the quality of the wound scar. Thus, a better understanding of the contribution of kinins to skin wound healing may reveal novel options for therapy. PMID- 26817700 TI - Self-assembled systems of water soluble metal 8-hydroxyquinolates with surfactants and conjugated polyelectrolytes. AB - We have studied the interaction of 8-hydroxyquinoline-5-sulfonate (8-HQS) with the metal ions Al(iii) and Zn(ii) in aqueous solution in the presence of tetraalkylammonium surfactants using UV/vis absorption, fluorescence, NMR spectroscopy and electrical conductivity measurements, complemented by DFT calculations and molecular dynamics (MD) simulations. Under appropriate conditions, complexes between 8-HQS and metal ions form rapidly, and have similar electronic, spectroscopic and photophysical properties to the corresponding metal quinolates, such as Alq3. These interact with the cationic surfactants, leading to marked increases in fluorescence intensity. However, significant differences are seen in the behavior of the two metal ions. With aluminium, a stable [Al(8 QS)3](3-) anion is formed, and interacts, predominantly through electrostatic interactions, with the surfactant, without disrupting the metal ion coordination sphere. In contrast, with Zn(ii), there is a competition between the metal ion and surfactants in the interaction with 8-HQS, although the [Zn(8-QS)2(H2O)2](2-) species is stable at appropriate pH and surfactant concentration. The studies are extended to systems with the conjugated polyelectrolyte (CPE) poly-(9,9-bis(6 N,N,N-trimethylammonium)hexyl)-fluorene-phenylene bromide (HTMA-PFP), which has a similar alkylammonium chain to the surfactants. Mixing metal salt, 8-HQS and HTMA PFP in the presence of a nonionic surfactant leads to the formation of a metal complex/CPE supramolecular assembly between the conjugated polyelectrolyte and the metal/8-HQS complex, as demonstrated by electronic energy transfer. The potential of these systems in sensing, light harvesting, and electron injection/transport layers in organic semiconductor devices is discussed. PMID- 26817701 TI - Lst1 deficiency has a minor impact on course and outcome of the host response to influenza A H1N1 infections in mice. AB - BACKGROUND: Previously, we performed a quantitative trait locus (QTL) mapping study in BXD recombinant inbred mice to identify host genetic factors that confer resistance to influenza A virus infection. We found Lst1 (leukocyte specific transcript 1) as one of the most promising candidate genes in the Qivr17-2 locus because it is non-functional in DBA/2 J mice. Several studies have proposed that LST1 plays a role in the immune response to inflammatory diseases in humans and has additional immune-regulatory functions. Here, we evaluated the relevance of LST1 for the host response to influenza A infection in B6-Lst1 (-/-) mutant mice. FINDINGS: To investigate the role of LST1, we infected B6-Lst1 (-/-) mutant and C57BL/6 N wild-type mice with a low-virulent influenza A virus (PR8M; H1N1). Lst1 deficient mice exhibited significantly increased body weight loss at days 5 and 6 after infection and slightly increased lethality compared to infected wild-type mice. Determination of viral loads, histopathological examination and analysis of immune cell composition in bronchoalveolar lavage of infected lungs did not reveal any obvious differences between KO and wild-type mice. CONCLUSIONS: The absence of Lst1 leads to a slightly more susceptible phenotype. However, deletion of Lst1 in DBA/2 J mice alone does not explain the high susceptibility of this strain to PR8M influenza infections. PMID- 26817702 TI - Editing Plant Genomes: a new era of crop improvement. PMID- 26817704 TI - Twenty year follow-up of ACL reconstruction (AJSM)--the evidence of experience. PMID- 26817705 TI - Architectural adaptations of muscle to training and injury: a narrative review outlining the contributions by fascicle length, pennation angle and muscle thickness. AB - BACKGROUND: The architectural characteristics of muscle (fascicle length, pennation angle muscle thickness) respond to varying forms of stimuli (eg, training, immobilisation and injury). Architectural changes following injury are thought to occur in response to the restricted range of motion experienced during rehabilitation and the associated neuromuscular inhibition. However, it is unknown if these differences exist prior to injury, and had a role in injury occuring (prospectively), or if they occur in response to the incident itself (retrospectively). Considering that the structure of a muscle will influence how it functions, it is of interest to understand how these architectural variations may alter how a muscle acts with reference to the force-length and force-velocity relationships. OBJECTIVES: Our narrative review provides an overview of muscle architectural adaptations to training and injury. Specifically, we (1) describe the methods used to measure muscle architecture; (2) detail the impact that architectural alterations following training interventions, immobilisation and injury have on force production and (3) present a hypothesis on how neuromuscular inhibition could cause maladaptations to muscle architecture following injury. PMID- 26817706 TI - Great Britain Rowing Team Guideline for Diagnosis and Management of Rib Stress Injury: Part 2 - The Guideline itself. PMID- 26817707 TI - Clinical utility of RAS mutations in thyroid cancer: a blurred picture now emerging clearer. AB - RAS mutations play an important role in thyroid tumorigenesis. Considerable effort has been made in the last decade to apply RAS mutations as molecular markers to the clinical management of thyroid nodules and thyroid cancer. Yet, for the low diagnostic sensitivities and specificities of RAS mutations, when used alone, and for their uncertain role in the clinical outcomes of thyroid cancer, it has been unclear how to appropriately use them to assist the management of thyroid nodules and thyroid cancer. Studies from recent years, now added from the Alexander group, have shed light on this issue, making a blurred clinical picture now emerge clearer-RAS mutations, when combined with other genetic markers, have high diagnostic negative predictive values for thyroid cancer; cytologically benign thyroid nodules, including those positive for RAS mutations, have long-term clinical stability when non-surgically managed; and differentiated thyroid cancers harboring RAS mutations alone have an excellent prognosis. This progress in understanding RAS mutations in thyroid cancer is showing a major impact on molecular-based practice in the management of thyroid cancer.Please see related research articles: http://dx.doi.org/10.1186/s12916-016 0554-1 and http://dx.doi.org/10.1186/s12916-015-0419-z. PMID- 26817708 TI - Medoidshift clustering applied to genomic bulk tumor data. AB - Despite the enormous medical impact of cancers and intensive study of their biology, detailed characterization of tumor growth and development remains elusive. This difficulty occurs in large part because of enormous heterogeneity in the molecular mechanisms of cancer progression, both tumor-to-tumor and cell to-cell in single tumors. Advances in genomic technologies, especially at the single-cell level, are improving the situation, but these approaches are held back by limitations of the biotechnologies for gathering genomic data from heterogeneous cell populations and the computational methods for making sense of those data. One popular way to gain the advantages of whole-genome methods without the cost of single-cell genomics has been the use of computational deconvolution (unmixing) methods to reconstruct clonal heterogeneity from bulk genomic data. These methods, too, are limited by the difficulty of inferring genomic profiles of rare or subtly varying clonal subpopulations from bulk data, a problem that can be computationally reduced to that of reconstructing the geometry of point clouds of tumor samples in a genome space. Here, we present a new method to improve that reconstruction by better identifying subspaces corresponding to tumors produced from mixtures of distinct combinations of clonal subpopulations. We develop a nonparametric clustering method based on medoidshift clustering for identifying subgroups of tumors expected to correspond to distinct trajectories of evolutionary progression. We show on synthetic and real tumor copy-number data that this new method substantially improves our ability to resolve discrete tumor subgroups, a key step in the process of accurately deconvolving tumor genomic data and inferring clonal heterogeneity from bulk data. PMID- 26817709 TI - Ruboxistaurin attenuates diabetic nephropathy via modulation of TGF-beta1/Smad and GRAP pathways. AB - OBJECTIVE: To investigate whether ruboxistaurin (a selective PKC-beta inhibitor) mediates renoprotective effect via interference with TGF-beta1/Smad-GRAP cross signalling. METHOD: Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (55 mg/kg). Then, the diabetic rats were treated with ruboxistaurin (10 mg/kg, p.o) for 6 weeks. Valsartan (15 mg/kg, p.o) was used as a positive control. After 6 weeks of treatment, diabetic nephropathy biomarkers were assessed. TGF-beta1, Smad2, and Smad3 mRNA and protein levels were detected using qPCR and western blot analysis. KEY FINDINGS: Data showed that serum creatinine, kidney/body weight ratio and urinary albumin excretion significantly increased in diabetic rats. These changes were significantly attenuated by treatment with ruboxistaurin. A significant up-regulation of TGF-beta1, Smad2 and Smad3 mRNA expression was observed in diabetic rats, which was alleviated by administration of ruboxistaurin. Furthermore, immunoblotting showed a significant improvement in protein levels of TGF-beta1 (P < 0.01), Smad2/3 (P < 0.01) and p Smad3 (P < 0.001) in diabetic rats treated with ruboxistaurin compared to untreated. Importantly, the reduction in GRAP protein expression in diabetic kidney was prevented by treatment with ruboxistaurin. CONCLUSION: These data suggest that the renoprotective effect of ruboxistaurin is possibly due to down regulation of TGF-beta1/Smad pathway and normalization of GRAP protein expression. PMID- 26817710 TI - Mirror-backed Dark Alumina: A Nearly Perfect Absorber for Thermoelectronics and Thermophotovotaics. AB - We present here a broadband, wide-angle, and polarization-independent nearly perfect absorber consisting of mirror-backed nanoporous alumina. By electrochemically anodizing the disordered multicomponent aluminum and properly tailoring the thickness and air-filling fraction of nanoporous alumina, according to the Maxwell-Garnet mixture theory, a large-area dark alumina can be made with excellent photothermal properties and absorption larger than 93% over a wide wavelength range spanning from near-infrared to ultraviolet light, i.e. 250 nm 2500 nm. The measured absorption is orders of magnitude greater than other reported anodized porous alumina, typically semi-transparent at similar wavelengths. This simple yet effective approach, however, does not require any lithography, nano-mixture deposition, pre- and post-treatment. Here, we also envisage and theoretically investigate the practical use of proposed absorbers and/or photothermal converters in integrated thermoelectronic and/or thermophotovoltaic energy conversion devices, which make efficient use of the entire spectrum of ambient visible to near-infrared radiation. PMID- 26817711 TI - Weakly supervised learning of biomedical information extraction from curated data. AB - BACKGROUND: Numerous publicly available biomedical databases derive data by curating from literatures. The curated data can be useful as training examples for information extraction, but curated data usually lack the exact mentions and their locations in the text required for supervised machine learning. This paper describes a general approach to information extraction using curated data as training examples. The idea is to formulate the problem as cost-sensitive learning from noisy labels, where the cost is estimated by a committee of weak classifiers that consider both curated data and the text. RESULTS: We test the idea on two information extraction tasks of Genome-Wide Association Studies (GWAS). The first task is to extract target phenotypes (diseases or traits) of a study and the second is to extract ethnicity backgrounds of study subjects for different stages (initial or replication). Experimental results show that our approach can achieve 87% of Precision-at-2 (P@2) for disease/trait extraction, and 0.83 of F1-Score for stage-ethnicity extraction, both outperforming their cost-insensitive baseline counterparts. CONCLUSIONS: The results show that curated biomedical databases can potentially be reused as training examples to train information extractors without expert annotation or refinement, opening an unprecedented opportunity of using "big data" in biomedical text mining. PMID- 26817712 TI - Toughness and strength of nanocrystalline graphene. AB - Pristine monocrystalline graphene is claimed to be the strongest material known with remarkable mechanical and electrical properties. However, graphene made with scalable fabrication techniques is polycrystalline and contains inherent nanoscale line and point defects--grain boundaries and grain-boundary triple junctions--that lead to significant statistical fluctuations in toughness and strength. These fluctuations become particularly pronounced for nanocrystalline graphene where the density of defects is high. Here we use large-scale simulation and continuum modelling to show that the statistical variation in toughness and strength can be understood with 'weakest-link' statistics. We develop the first statistical theory of toughness in polycrystalline graphene, and elucidate the nanoscale origins of the grain-size dependence of its strength and toughness. Our results should lead to more reliable graphene device design, and provide a framework to interpret experimental results in a broad class of two-dimensional materials. PMID- 26817713 TI - Structure sensitivity in the nonscalable regime explored via catalysed ethylene hydrogenation on supported platinum nanoclusters. AB - The sensitivity, or insensitivity, of catalysed reactions to catalyst structure is a commonly employed fundamental concept. Here we report on the nature of nano catalysed ethylene hydrogenation, investigated through experiments on size selected Ptn (n=8-15) clusters soft-landed on magnesia and first-principles simulations, yielding benchmark information about the validity of structure sensitivity/insensitivity at the bottom of the catalyst size range. Both ethylene hydrogenation-to-ethane and the parallel hydrogenation-dehydrogenation ethylidyne producing route are considered, uncovering that at the <1 nm size-scale the reaction exhibits characteristics consistent with structure sensitivity, in contrast to structure insensitivity found for larger particles. The onset of catalysed hydrogenation occurs for Ptn (n >= 10) clusters at T>150 K, with maximum room temperature reactivity observed for Pt13. Structure insensitivity, inherent for specific cluster sizes, is induced in the more active Pt13 by a temperature increase up to 400 K leading to ethylidyne formation. Control of sub nanometre particle size may be used for tuning catalysed hydrogenation activity and selectivity. PMID- 26817714 TI - Maternal Serum Zinc Concentration during Pregnancy Is Inversely Associated with Risk of Preterm Birth in a Chinese Population. AB - BACKGROUND: Evidence exists that maternal zinc status during pregnancy is linked to adverse pregnancy outcomes including abortion, fetal growth restriction, and neural tube defects. However, it remains unclear whether maternal serum zinc concentration (SZC) during pregnancy is associated with risk of preterm birth. OBJECTIVE: This study was designed to investigate the association between maternal SZC during pregnancy and risk of preterm birth. METHODS: For this substudy of the China-Anhui Birth Cohort Study, 3081 maternal-singleton pairs with detailed birth records and available serum samples were identified. The maternal SZC was determined with flame atomic absorption spectroscopy. A total of 169 preterm births were identified. In this study, the women were divided into tertiles on the basis of their SZC: low (<76.7 MUg/dL), medium (76.7-99.6 MUg/dL), and high (>=99.7 MUg/dL). The ORs for preterm birth were estimated by using multiple logistic regression models. RESULTS: The median SZC was 87.3 MUg/dL (range: 11.1-211 MUg/dL). Incidences of preterm birth were 7.3% and 6.0% among subjects with low and medium SZCs, respectively, which were significantly higher than 3.1% among subjects with a high SZC [ORs (95% CIs) for low and medium SZCs: 2.45 (1.60, 3.74), P < 0.001, and 2.00 (1.29, 3.09), P < 0.01, respectively]. After adjustment for prepregnancy body mass index, maternal age, time of serum collection, gravidity, parity, and monthly income, adjusted ORs were 2.41 (95% CI: 1.57, 3.70; P < 0.001) and 1.97 (95% CI: 1.27, 3.05; P < 0.01) among subjects with low and medium maternal SZCs. CONCLUSIONS: Maternal serum zinc concentration during pregnancy is inversely associated with risk of preterm birth in the Chinese population, and the results are driven by maternal SZC in the first trimester. PMID- 26817715 TI - Gaussian Graphical Models Identify Networks of Dietary Intake in a German Adult Population. AB - BACKGROUND: Data-reduction methods such as principal component analysis are often used to derive dietary patterns. However, such methods do not assess how foods are consumed in relation to each other. Gaussian graphical models (GGMs) are a set of novel methods that can address this issue. OBJECTIVE: We sought to apply GGMs to derive sex-specific dietary intake networks representing consumption patterns in a German adult population. METHODS: Dietary intake data from 10,780 men and 16,340 women of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort were cross-sectionally analyzed to construct dietary intake networks. Food intake for each participant was estimated using a 148-item food-frequency questionnaire that captured the intake of 49 food groups. GGMs were applied to log-transformed intakes (grams per day) of 49 food groups to construct sex-specific food networks. Semiparametric Gaussian copula graphical models (SGCGMs) were used to confirm GGM results. RESULTS: In men, GGMs identified 1 major dietary network that consisted of intakes of red meat, processed meat, cooked vegetables, sauces, potatoes, cabbage, poultry, legumes, mushrooms, soup, and whole-grain and refined breads. For women, a similar network was identified with the addition of fried potatoes. Other identified networks consisted of dairy products and sweet food groups. SGCGMs yielded results comparable to those of GGMs. CONCLUSIONS: GGMs are a powerful exploratory method that can be used to construct dietary networks representing dietary intake patterns that reveal how foods are consumed in relation to each other. GGMs indicated an apparent major role of red meat intake in a consumption pattern in the studied population. In the future, identified networks might be transformed into pattern scores for investigating their associations with health outcomes. PMID- 26817716 TI - Consumption of Fish Oil Providing Amounts of Eicosapentaenoic Acid and Docosahexaenoic Acid That Can Be Obtained from the Diet Reduces Blood Pressure in Adults with Systolic Hypertension: A Retrospective Analysis. AB - BACKGROUND: Although many randomized controlled trials (RCTs) have examined the effects of the n-3 (omega-3) fatty acids eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) on blood pressure (BP) and vascular function, the majority have used doses of EPA+DHA of >3 g/d, which are unlikely to be achieved by dietary manipulation. OBJECTIVE: The objective was to examine, by using a retrospective analysis from a multicenter RCT, the impact of recommended EPA+DHA intakes achievable through diet on systolic and diastolic BPs and microvascular function in adults in the United Kingdom. METHODS: In a double blind, placebo-controlled RCT, healthy men and women (n = 312) consumed a control oil or fish oil (FO) providing 0.7 or 1.8 g EPA+DHA/d, in random order, each for 8 wk. Fasting BP and microvascular function (using laser Doppler iontophoresis) were assessed and plasma collected for the quantification of markers of vascular function. Participants were retrospectively genotyped for the endothelial nitric oxide synthase (eNOS) rs1799983 variant. RESULTS: No effects of n-3 fatty acid treatment or any treatment * eNOS genotype interactions were evident in the group as a whole for any of the clinical or biochemical outcomes. Assessment of response according to hypertension status at baseline indicated a significant (P = 0.046) FO-induced reduction (mean: 5 mm Hg) in systolic BP, specifically in those with isolated systolic hypertension (n = 31). No dose response was observed. CONCLUSIONS: These findings indicate that in adults with isolated systolic hypertension, daily doses of EPA+DHA as low as 0.7 g show clinically meaningful BP reductions, which, at a population level, could be associated with lower cardiovascular disease risk. Confirmation of findings in an RCT in which participants are prospectively recruited on the basis of BP status is required to draw definite conclusions. PMID- 26817717 TI - Evidence from a Randomized Trial That Exposure to Supplemental Folic Acid at Recommended Levels during Pregnancy Does Not Lead to Increased Unmetabolized Folic Acid Concentrations in Maternal or Cord Blood. AB - BACKGROUND: Exposure to higher intakes of folic acid (FA) from fortified foods and supplements, although largely considered beneficial, is associated with unmetabolized FA in the circulation, which has raised some health concerns. OBJECTIVE: The effect of supplemental FA at a dose of 400 MUg/d during pregnancy on unmetabolized FA concentrations in maternal plasma and newborn cord blood plasma was investigated. METHODS: A new analysis was performed of blood samples from participants in a randomized trial in pregnancy. Women aged 18-35 y, who had taken 400 MUg FA/d as recommended in the first trimester, were recruited at the start of trimester 2 and randomly allocated to receive either 400 MUg FA/d (n = 59) or a placebo (n = 67) throughout the second and third trimesters until delivery. Unmetabolized FA concentrations in maternal and cord blood samples were measured by LC-tandem MS analysis. RESULTS: In response to the intervention from gestational week 14 through delivery, a higher proportion of women in the FA compared with the placebo group had detectable FA (>=0.27 nmol/L) in plasma, but the difference in concentrations was not statistically significant (mean +/- SD: 0.44 +/- 0.80 compared with 0.13 +/- 0.49 nmol/L, P = 0.38). FA treatment throughout pregnancy resulted in higher cord blood plasma total folate (50.6 +/- 20.1 compared with 34.5 +/- 14.4 nmol/L; P = 0.004) and 5-methyltetrahydrofolate (50.4 +/- 20.3 compared with 34.5 +/- 14.4 nmol/L; P = 0.005) concentrations, but FA was detected only in 8 of 53 available cord blood samples, and the proportion of samples with detectable FA concentrations was similar in FA-treated and placebo groups. CONCLUSIONS: Plasma concentrations of unmetabolized FA arising from supplemental FA at a dose of 400 MUg/d, in addition to FA from fortified foods, were low or undetectable in mothers and newborns. The benefits for mothers and offspring of continuing FA supplementation beyond the first trimester of pregnancy can be achieved without posing any risk of increasing unmetabolized circulating FA, even in those already exposed to FA from fortified foods. PMID- 26817718 TI - Weight Status and Alcohol Intake Modify the Association between Vitamin D and Breast Cancer Risk. AB - BACKGROUND: Mechanistic hypotheses suggest that vitamin D may contribute to the prevention of breast cancer. However, epidemiologic evidence is inconsistent, suggesting a potential effect modification by individual factors. OBJECTIVE: Our objective was to perform exploratory analyses on the prospective associations between the plasma 25-hydroxyvitamin D [25(OH)D] concentration, polymorphisms of genes encoding for the vitamin D receptor (VDR) and vitamin D-binding protein (also known as gc-globulin or group-specific component, GC), and breast cancer risk, along with 2 potential modifiers: body mass index (BMI; in kg/m(2)) and alcohol intake. METHODS: A nested case-control study was set up in the SUpplementation en VItamines et Mineraux Anti-oXydants (SU.VI.MAX) cohort (1994 2007), involving 233 women with breast cancer and 466 matched controls (mean +/- SD age: 49 +/- 6 y). The plasma total 25(OH)D concentration and gene polymorphisms were assessed on samples obtained at baseline. Conditional logistic regression models were computed. RESULTS: A higher plasma 25(OH)D concentration was associated with a decreased risk of breast cancer for women with a BMI < the median of 22.4 [OR quartile (Q)4 compared with Q1: 0.46; 95% CI: 0.23, 0.89; P trend = 0.01, P-interaction = 0.002], whereas it was associated with an increased risk for women with a BMI >= the median (OR Q4 compared with Q1: 2.45; 95% CI: 1.13, 5.28; P-trend = 0.02, P-interaction = 0.002). A plasma 25(OH)D concentration >= 10 ng/mL was associated with a decreased risk of breast cancer for women with alcohol intakes >= the median of 7.1 g/d (OR >=10 compared with <10 ng/mL: 0.50; 95% CI: 0.26, 0.95; P = 0.03, P-interaction = 0.03). The genetic analyses were consistent with the results observed with plasma 25(OH)D. CONCLUSION: In this prospective study, BMI and alcohol intake modified the association between vitamin D [plasma 25(OH)D and vitamin D-related gene polymorphisms] and breast cancer risk. These effect modifications suggest explanations for discrepancies in results of previous studies. This trial was registered at clinicaltrials.gov as NCT00272428. PMID- 26817719 TI - RGS proteins as targets in the treatment of intestinal inflammation and visceral pain: New insights and future perspectives. AB - Regulators of G protein signaling (RGS) proteins provide timely termination of G protein-coupled receptor (GPCR) responses. Serving as a central control point in GPCR signaling cascades, RGS proteins are promising targets for drug development. In this review, we discuss the involvement of RGS proteins in the pathophysiology of the gastrointestinal inflammation and their potential to become a target for anti-inflammatory drugs. Specifically, we evaluate the emerging evidence for modulation of selected receptor families: opioid, cannabinoid and serotonin by RGS proteins. We discuss how the regulation of RGS protein level and activity may modulate immunological pathways involved in the development of intestinal inflammation. Finally, we propose that RGS proteins may serve as a prognostic factor for survival rate in colorectal cancer. The ideas introduced in this review set a novel conceptual framework for the utilization of RGS proteins in the treatment of gastrointestinal inflammation, a growing major concern worldwide. PMID- 26817720 TI - Microbiome and Biocatalytic Bacteria in Monkey Cup (Nepenthes Pitcher) Digestive Fluid. AB - Tropical carnivorous plant, Nepenthes, locally known as "monkey cup", utilises its pitcher as a passive trap to capture insects. It then secretes enzymes into the pitcher fluid to digest the insects for nutrients acquisition. However, little is known about the microbiota and their activity in its pitcher fluid. Eighteen bacteria phyla were detected from the metagenome study in the Nepenthes pitcher fluid. Proteobacteria, Bacteroidetes and Actinobacteria are the dominant phyla in the Nepenthes pitcher fluid. We also performed culturomics approach by isolating 18 bacteria from the Nepenthes pitcher fluid. Most of the bacterial isolates possess chitinolytic, proteolytic, amylolytic, and cellulolytic and xylanolytic activities. Fifteen putative chitinase genes were identified from the whole genome analysis on the genomes of the 18 bacteria isolated from Nepenthes pitcher fluid and expressed for chitinase assay. Of these, six clones possessed chitinase activity. In conclusion, our metagenome result shows that the Nepenthes pitcher fluid contains vast bacterial diversity and the culturomic studies confirmed the presence of biocatalytic bacteria within the Nepenthes pitcher juice which may act in symbiosis for the turn over of insects trapped in the Nepenthes pitcher fluid. PMID- 26817722 TI - Weak Genetic Explanation 20 Years Later: Reply to Plomin et al. (2016). AB - Plomin, DeFries, Knopik, and Neiderhiser (2016, this issue) are correct in their assertion that many discoveries of behavior genetics have proven to be robust and replicable. I note, in contrast, that more specific assertions about the role of genetics in the development of behavior have failed to replicate. Reflecting on why more general findings replicate better than specific ones sheds light on the difficulties of studying complex human development and on the role played by genes in determining its course. PMID- 26817723 TI - Why Behavioral Genetics Matters: Comment on Plomin et al. (2016). PMID- 26817724 TI - What Scientists Who Study Emotion Agree About. AB - In recent years, the field of emotion has grown enormously-recently, nearly 250 scientists were identified who are studying emotion. In this article, I report a survey of the field, which revealed high agreement about the evidence regarding the nature of emotion, supporting some of both Darwin's and Wundt's 19th century proposals. Topics where disagreements remain were also exposed. PMID- 26817721 TI - Top 10 Replicated Findings From Behavioral Genetics. AB - In the context of current concerns about replication in psychological science, we describe 10 findings from behavioral genetic research that have replicated robustly. These are "big" findings, both in terms of effect size and potential impact on psychological science, such as linearly increasing heritability of intelligence from infancy (20%) through adulthood (60%). Four of our top 10 findings involve the environment, discoveries that could have been found only with genetically sensitive research designs. We also consider reasons specific to behavioral genetics that might explain why these findings replicate. PMID- 26817726 TI - On the Use and Usefulness of Backup Plans. AB - In this article, we introduce the concept of backup plans as a motivational construct, defined as alternative means to an end that are intentionally developed but are not initially (or ever) used. We posit that backup plans change the way that a person pursues a goal, as well as the likelihood of achieving it, even if the backup plans are never used. In some cases, backup plans are a safety net supporting goal pursuit; however, in other cases, they constitute an unnecessary expense that can undermine motivation to persist with a first-choice plan. We propose that variations in the use and usefulness of backup plans are based on a person's estimation and regulation of complexity value, or the additional costs and benefits that having a backup plan introduces compared with pursuing the same goal with only a single means. Although variations in the estimation and regulation of complexity value are idiosyncratic products of individual, contextual, and goal-related factors, we provide the prototypical example of age-related differences to illustrate our key points. In sum, our conceptualization of backup plans represents a new synthesis of motivation, multiple-goal, and life-span developmental research that addresses a key lacuna in the self-regulation literature. PMID- 26817725 TI - Situational Strategies for Self-Control. AB - Exercising self-control is often difficult, whether declining a drink in order to drive home safely, passing on the chocolate cake to stay on a diet, or ignoring text messages to finish reading an important paper. But enacting self-control is not always difficult, particularly when it takes the form of proactively choosing or changing situations in ways that weaken undesirable impulses or potentiate desirable ones. Examples of situational self-control include the partygoer who chooses a seat far from where drinks are being poured, the dieter who asks the waiter not to bring around the dessert cart, and the student who goes to the library without a cell phone. Using the process model of self-control, we argue that the full range of self-control strategies can be organized by considering the timeline of the developing tempting impulse. Because impulses tend to grow stronger over time, situational self-control strategies-which can nip a tempting impulse in the bud-may be especially effective in preventing undesirable action. Ironically, we may underappreciate situational self-control for the same reason it is so effective-namely, that by manipulating our circumstances to advantage, we are often able to minimize the in-the-moment experience of intrapsychic struggle typically associated with exercising self-control. PMID- 26817727 TI - A Working Memory System With Distributed Executive Control. AB - Working memory consists of domain-specific storage facilities and domain-general executive control processes. In some working memory theories, these control processes are accounted for via a homunculus, the central executive. In the present article, the author defends a mechanistic view of executive control by adopting the position that executive control is situated in the context of goal directed behavior to maintain and protect the goal and to select an action to attain the goal. On the basis of findings in task switching and dual tasking, he proposes an adapted multicomponent working memory model in which the central executive is replaced by three interacting components: an executive memory that maintains the task set, a collection of acquired procedural rules, and an engine that executes the procedural rules that match the ensemble of working memory contents. The strongest among the rules that match the ensemble of working memory contents is applied, resulting in changes of the working memory contents or in motor actions. According to this model, goals are attained when the route to the goals is known or can be searched when the route is unknown (problem solving). Empirical evidence for this proposal and new predictions are discussed. PMID- 26817728 TI - Emotions and Decisions: Beyond Conceptual Vagueness and the Rationality Muddle. AB - For centuries, decision scholars paid little attention to emotions: Decisions were modeled in normative and descriptive frameworks with little regard for affective processes. Recently, however, an "emotions revolution" has taken place, particularly in the neuroscientific study of decision making, putting emotional processes on an equal footing with cognitive ones. Yet disappointingly little theoretical progress has been made. The concepts and processes discussed often remain vague, and conclusions about the implications of emotions for rationality are contradictory and muddled. We discuss three complementary ways to move the neuroscientific study of emotion and decision making from agenda setting to theory building. The first is to use reverse inference as a hypothesis-discovery rather than a hypothesis-testing tool, unless its utility can be systematically quantified (e.g., through meta-analysis). The second is to capitalize on the conceptual inventory advanced by the behavioral science of emotions, testing those concepts and unveiling the underlying processes. The third is to model the interplay between emotions and decisions, harnessing existing cognitive frameworks of decision making and mapping emotions onto the postulated computational processes. To conclude, emotions (like cognitive strategies) are not rational or irrational per se: How (un)reasonable their influence is depends on their fit with the environment. PMID- 26817729 TI - A Case for Thinking Without Consciousness. AB - People can engage in prolonged thought processes, such as when they are facing an important decision or when they are working on a scientific discovery. Such thought processes can take months or even years. We argue that while people engage in such thinking, they make progress not only when they consciously think but also sometimes when they are consciously thinking about something else-that is, while they think unconsciously. We review the literature on unconscious thought (UT) processes and conclude that there is indeed quite some evidence for UT. Conceptualized as a form of unconscious goal pursuit, UT is likely to be especially fruitful for thought processes that are complex, important, or interesting to the thinker. In addition, we discuss other characteristics of the UT process. We end with proposing Type 3 processes, in addition to Type 1 and Type 2 (or Systems 1 and 2) processes, to accommodate prolonged thought processes in models on thought. PMID- 26817730 TI - Combining Reaction Time and Accuracy: The Relationship Between Working Memory Capacity and Task Switching as a Case Example. AB - It is generally agreed upon that the mechanisms underlying task switching heavily depend on working memory, yet numerous studies have failed to show a strong relationship between working memory capacity (WMC) and task-switching ability. We argue that this relationship does indeed exist but that the dependent variable used to measure task switching is problematic. To support our claim, we reanalyzed data from two studies with a new scoring procedure that combines reaction time (RT) and accuracy into a single score. The reanalysis revealed a strong relationship between task switching and WMC that was not present when RT based switch costs were used as the dependent variable. We discuss the theoretical implications of this finding along with the potential uses and limitations of the scoring procedure we used. More broadly, we emphasize the importance of using measures that incorporate speed and accuracy in other areas of research, particularly in comparisons of subjects differing in cognitive and developmental levels. PMID- 26817731 TI - Introduction to the Registered Replication Report: Hart & Albarracin (2011). PMID- 26817734 TI - Reversal of Orbital Symmetry Control in Electrocyclic Ring Closures through Craig Mobius Aromaticity. AB - Experimentalists are challenged to find the organometallic thermal electrocyclizations that are computationally predicted to proceed with opposite stereoselectivity compared to their metal-free parent 4n and 4n+2 pi-electron systems. While ring closure of, for example, s-cis-butadiene proceeds conrotatory, an iron alkyl complex formed by replacement of a (CH) unit by an [FeH] metal fragment results in a disrotatory electrocyclization. PMID- 26817732 TI - Registered Replication Report: Hart & Albarracin (2011). AB - Language can be viewed as a complex set of cues that shape people's mental representations of situations. For example, people think of behavior described using imperfective aspect (i.e., what a person was doing) as a dynamic, unfolding sequence of actions, whereas the same behavior described using perfective aspect (i.e., what a person did) is perceived as a completed whole. A recent study found that aspect can also influence how we think about a person's intentions (Hart & Albarracin, 2011). Participants judged actions described in imperfective as being more intentional (d between 0.67 and 0.77) and they imagined these actions in more detail (d = 0.73). The fact that this finding has implications for legal decision making, coupled with the absence of other direct replication attempts, motivated this registered replication report (RRR). Multiple laboratories carried out 12 direct replication studies, including one MTurk study. A meta-analysis of these studies provides a precise estimate of the size of this effect free from publication bias. This RRR did not find that grammatical aspect affects intentionality (d between 0 and -0.24) or imagery (d = -0.08). We discuss possible explanations for the discrepancy between these results and those of the original study. PMID- 26817735 TI - Nesiritide in patients hospitalized for acute heart failure: does timing matter? Implication for future acute heart failure trials. AB - AIMS: It remains unclear if early administration of i.v. nesiritide in patients hospitalized with acute heart failure (AHF) is associated with improved clinical outcomes. METHODS AND RESULTS: We analysed data from 7007 patients enrolled in ASCEND-HF to examine the associations between time to treatment with study medication (nesiritide or placebo) and clinical endpoints: (i) moderate to marked dyspnoea relief on a 7-point Likert scale at 6 h; (ii) 30-day all-cause mortality or re-hospitalization; and (iii) 30-day all-cause mortality. The median time to study drug administration was 16.7 h (25th, 75th percentiles = 6.5, 23.1), with significant regional variation (e.g. median of 13.0 h in Asia-Pacific vs. 18.4 h in North America). After risk adjustment, each hour delay in study medication after the first 10 h from initial hospital presentation was associated with modestly reduced odds of dyspnoea relief [(adjusted odds ratio (OR) 0.98, 95% confidence interval (CI) 0.98-0.99; P < 0.0001]. Every hour delay in study medication was associated with modestly higher all-cause mortality or re hospitalization (unadjusted OR 1.01, 95% CI 1.01-1.02; P < 0.001) due to pre randomization therapies and known predictors of 30-day outcomes (adjusted P = 0.12). There was no significant association between time to study drug and all cause mortality (P > 0.08). CONCLUSION: In a large international AHF trial, time to treatment with study medication varied markedly across regions. Earlier administration of study medication was associated with modestly better dyspnoea relief, but not 30-day clinical outcomes. The association between timing of treatment with study medication and study endpoints may have implications for the interpretation of AHF studies and future trial design. PMID- 26817736 TI - Changes in Body Mass Index and the Trajectory of Depressive Symptoms Among Rural Men and Women. AB - PURPOSE: This study examined the association between body mass index (BMI) changes over time and the risk of elevated depressive symptoms in a cohort of Midwestern rural adults. METHODS: The longitudinal study used data from a telephone survey in 2005 including 1,475 men and women enrolled in the Walk the Ozarks to Wellness Project from 12 rural communities in Missouri, Arkansas, and Tennessee. Multilevel random intercept mixed models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the association between BMI calculated from self-reported height and body weight and elevated depressive symptoms, adjusting for sociodemographic, behavioral, and medical variables. FINDINGS: Elevated depressive symptoms were common in this rural population (17%-19%) and the mean BMI was 28 kg/m2 . For each unit increase in BMI over time, representing an average increase of about 5.8 pounds from baseline weight, there was a 6% increased odds of elevated depressive symptoms (aOR: 1.06, 95% CI: 1.02-1.12). CONCLUSIONS: Our findings hold important public health implications given the increasing rates of overweight and obesity over the past couple of decades, particularly among rural adults. PMID- 26817737 TI - Lysine acetylation of the Mycobacterium tuberculosis HU protein modulates its DNA binding and genome organization. AB - Nucleoid-associated protein HU, a conserved protein across eubacteria is necessary for maintaining the nucleoid organization and global regulation of gene expression. Mycobacterium tuberculosis HU (MtHU) is distinct from the other orthologues having 114 amino acid long carboxyl terminal extensions with a high degree of sequence similarity to eukaryotic histones. In this study, we demonstrate that the DNA binding property of MtHU is regulated by posttranslational modifications akin to eukaryotic histones. MtHU purified from M. tuberculosis cells is found to be acetylated on multiple lysine residues unlike the E. coli expressed recombinant protein. Using coimmunoprecipitation assay, we identified Eis as one of the acetyl transferases that interacts with MtHU and modifies it. Although Eis is known to acetylate aminoglycosides, the kinetics of acetylation showed that its protein acetylation activity on MtHU is robust. In vitro Eis modified MtHU at various lysine residues, primarily those located at the carboxyl terminal domain. Acetylation of MtHU caused reduced DNA interaction and alteration in DNA compaction ability of the NAP. Over-expression of the Eis leads to hyperacetylation of HU and decompaction of genome. These results provide first insights into the modulation of the nucleoid structure by lysine acetylation in bacteria. PMID- 26817738 TI - The Effect of Men's Body Attitudes and Motivation for Gym Attendance. AB - Caudwell, KM and Keatley, DA. The effect of men's body attitudes and motivation for gym attendance. J Strength Cond Res 30(9): 2550-2556, 2016-The current study integrates men's body attitudes with implicitly and explicitly measured motivation to investigate the role of these factors in predicting gym attendance. Male participants (N = 99) who regularly attended a gym were recruited to participate in an online questionnaire. Participants completed implicit and explicit measures of motivation, explicitly measured men's body attitudes, and reported the average number of gym visits per week. Attitudes related to body fat and explicitly measured autonomous motivation significantly predicted typical gym attendance. Implicitly measured motivation significantly and negatively predicted gym attendance. Results indicate some support for a dual-systems account of gym attendance. Men's body attitudes and autonomous motivation influences gym attendance; however, implicitly measured motivation showed antagonistic effects. Although individuals may explicitly state their autonomous motivation for gym attendance, attendance may also be influenced at the explicit level. Health and fitness professionals may improve gym attendance by focusing on people's reasons for attending a gym, facilitating autonomous motivation in clients, and minimizing the influence of controlled reasons for exercise. PMID- 26817739 TI - Time-Motion and Biological Responses in Simulated Mixed Martial Arts Sparring Matches. AB - Coswig, VS, Ramos, SdP, and Del Vecchio, FB. Time-motion and biological responses in simulated mixed martial arts sparring matches. J Strength Cond Res 30(8): 2156 2163, 2016-Simulated matches are a relevant component of training for mixed martial arts (MMA) athletes. This study aimed to characterize time-motion responses and investigate physiological stress and neuromuscular changes related to MMA sparring matches. Thirteen athletes with an average age of 25 +/- 5 years, body mass of 81.3 +/- 9.5 kg, height of 176.2 +/- 5.5 cm, and time of practice in MMA of 39 +/- 25 months participated in the study. The fighters executed three 5 minute rounds with 1-minute intervals. Blood and salivary samples were collected and physical tests and psychometric questionnaires administered at 3 time points: before (PRE), immediately after (POST), and 48 hours after the combat (48 h). Statistical analysis applied analysis of variance for repeated measurements. In biochemical analysis, significant changes (p <= 0.05) were identified between PRE and POST (glucose: 80.3 +/- 12.7 to 156.5 +/- 19.1 mg.ml; lactate: 4 +/- 1.7 to 15.6 +/- 4.8 mmol.dl), POST and 48 hours (glucose: 156.5 +/- 19.1 to 87.6 +/- 15.5 mg.ml; lactate: 15.6 +/- 4.8 to 2.9 +/- 3.5 mmol.dl; urea: 44.1 +/- 8.9 to 36.3 +/- 7.8 mg.ml), and PRE and 48 hours (creatine kinase [CK]: 255.8 +/- 137.4 to 395.9 +/- 188.7 U/L). In addition, time-motion analyses showed a total high:low intensity of 1:2 and an effort:pause ratio of 1:3. In conclusion, simulated MMA sparring matches feature moderate to high intensity and a low degree of musculoskeletal damage, which can be seen by absence of physical performance and decrease in CK. Results of the study indicate that sparring training could be introduced into competitive microcycles to improve technical and tactical aspects of MMA matches, due to the high motor specificity and low muscle damage. PMID- 26817740 TI - Examining the External Training Load of an English Premier League Football Team With Special Reference to Acceleration. AB - Akenhead, R, Harley, J, and Tweddle, S. Examining the external training load of an English Premier League football team with special reference to acceleration. J Strength Cond Res 30(9): 2424-2432, 2016-Practitioners and coaches often use external training load variables such as distance run and the number of high speed running (HSR) activities to quantify football training. However, an important component of the external load may be overlooked when acceleration activities are not considered. The aim of this study was to describe the within microcycle distribution of external load, including acceleration, during in season 1-game weeks in an elite football team. Global Positioning System technology was used to collect time-motion data from 12 representative 7-day microcycles across a competitive season (48 training days, 295 data sets). Training time, total distance (TD), high-speed running (HSR) distance (>5.8 m.s), sprint running distance (>6.7 m.s) and acceleration variables were recorded during each training session. Data were analysed for interday and interposition differences using mixed linear modeling. The distribution of external load was characterized by the second training day of the microcycle (5 days prematch) exhibiting the highest values for all variables of training load, with the fourth day (1 day prematch) exhibiting the lowest values. Central midfield players covered ~8-16% greater TD than other positions excluding wide midfielders (p <= 0.03, d = 0.2-0.4) and covered ~17% greater distance accelerating 1-2 m.s than central defenders (p = 0.03, d = 0.7). When expressed relative to training duration and TD, the magnitude of interday and interposition differences were markedly reduced (p = 0.03, d = 0.2-0.3). When managing the distribution of training load, practitioners should be aware of the intensity of training sessions and consider the density of external load within sessions. PMID- 26817741 TI - Exercise Type Affects Cardiac Vagal Autonomic Recovery After a Resistance Training Session. AB - Mayo, X, Iglesias-Soler, E, Farinas-Rodriguez, J, Fernandez-del-Olmo, M, and Kingsley, JD. Exercise type affects cardiac vagal autonomic recovery after a resistance training session. J Strength Cond Res 30(9): 2565-2573, 2016 Resistance training sessions involving different exercises and set configurations may affect the acute cardiovascular recovery pattern. We explored the interaction between exercise type and set configuration on the postexercise cardiovagal withdrawal measured by heart rate variability and their hypotensive effect. Thirteen healthy participants (10 repetitions maximum [RM] bench press: 56 +/- 10 kg; parallel squat: 91 +/- 13 kg) performed 6 sessions corresponding to 2 exercises (Bench press vs. Parallel squat), 2 set configurations (Failure session vs. Interrepetition rest session), and a Control session of each exercise. Load (10RM), volume (5 sets), and rest (720 seconds) were equated between exercises and set configurations. Parallel squat produced higher reductions in cardiovagal recovery vs. Bench press (p = 0.001). These differences were dependent on the set configuration, with lower values in Parallel squat vs. Bench press for Interrepetition rest session (1.816 +/- 0.711 vs. 2.399 +/- 0.739 Ln HF/IRR * 10, p = 0.002), but not for Failure session (1.647 +/- 0.904 vs. 1.808 +/- 0.703 Ln HF/IRR * 10, p > 0.05). Set configuration affected the cardiovagal recovery, with lower values in Failure session in comparison with Interrepetition rest (p = 0.027) and Control session (p = 0.022). Postexercise hypotension was not dependent on the exercise type (p > 0.05) but was dependent on the set configuration, with lower values of systolic (p = 0.004) and diastolic (p = 0.011) blood pressure after the Failure session but not after an Interrepetition rest session in comparison with the Control session (p > 0.05). These results suggest that the exercise type and an Interrepetition rest design could blunt the decrease of cardiac vagal activity after exercise while exercising to muscular failure may contribute to the onset of postexercise hypotension. PMID- 26817742 TI - Adaptation to Damaging Dance and Repeated-Sprint Activity in Women. AB - Brown, MA, Howatson, G, Keane, KM, and Stevenson, EJ. Adaptation to damaging dance and repeated-sprint activity in women. J Strength Cond Res 30(9): 2574 2581, 2016-The repeated bout effect (RBE) refers to the prophylactic effect from damaging exercise after a single previous bout of exercise. There is a paucity of data examining the RBE in women, and investigations using exercise paradigms beyond isolated eccentric contractions are scarce. In light of the limited literature, this investigation aimed to determine whether 2 different sport specific exercise bouts would elicit a RBE in women. Twenty-one female dancers (19 +/- 1 years) completed either a dance-specific protocol (n = 10) or sport specific repeated-sprint protocol (n = 11). Delayed-onset muscle soreness (DOMS), limb girths, creatine kinase (CK), countermovement jump height, reactive strength index, maximal voluntary contraction, and 30-meter sprint time were recorded before and 0, 24, 48, and 72 hours after exercise. An identical exercise bout was conducted approximately 4 weeks after the initial bout, during which time the subjects maintained habitual training and dietary behaviors. DOMS and 30-meter sprint time decreased after a second bout of both activities (p = 0.003; (Equation is included in full-text article.)= 0.38 and p = 0.008; and (Equation is included in full-text article.)= 0.31, respectively). Circulating CK was also lower at 24, 48, and 72 hours after the second bout, independent of group (p = 0.010 and (Equation is included in full-text article.)= 0.23). Compared with the repeated-sprint protocol, the magnitude of change in DOMS was greater after a subsequent bout of the dance protocol (p = 0.010 and (Equation is included in full-text article.)= 0.19). These data are the first to demonstrate that dance and repeated-sprint activity resulting in muscle damage in women confers a protective effect against muscle damage after a subsequent bout. PMID- 26817743 TI - Contribution of Upper-Body Strength, Body Composition, and Maximal Oxygen Uptake to Predict Double Poling Power and Overall Performance in Female Cross-Country Skiers. AB - Osteras, S, Welde, B, Danielsen, J, van den Tillaar, R, Ettema, G, and Sandbakk, O. Contribution of upper-body strength, body composition, and maximal oxygen uptake to predict double poling power and overall performance in female cross country skiers. J Strength Cond Res 30(9): 2557-2564, 2016-Maximal oxygen uptake (V[Combining Dot Above]O2max) is regarded as the most performance-differentiating physiological measure in cross-country (XC) skiing. In addition, upper-body strength and lean mass have been associated with double poling (DP) power in XC skiers. In this study, we tested upper-body maximal strength, lean mass, and V[Combining Dot Above]O2max's contributions to predict DP power production of different durations and the overall XC skiing performance level of elite female XC skiers. Thirteen skiers (V[Combining Dot Above]O2max: 64.9 +/- 4.2 ml.kg.min) performed one 30-second and one 3-minute DP performance test using a ski ergometer. The International Ski Federation's (FIS) ranking points determined their overall XC skiing performance. The skiers performed three 1-repetition maximal strength tests in poling-specific exercises that isolated the elbow extension, shoulder extension, and trunk flexion movements. Body composition was determined by a DXA scan, and V[Combining Dot Above]O2max was tested in an incremental running test. Multiple regressions were used to predict power production in the 30-second and 3-minute tests and FIS points. The 2 best predictions of 30-second DP power were lean upper-body mass and maximal upper body strength (with the 3 strength tests normalized and pooled together as one variable) (R = 0.84 and 0.81, p < 0.001). Along with V[Combining Dot Above]O2max, the same 2 variables were the best predictions of both 3-minute DP power (R = 0.60 and 0.44, p <= 0.05) and overall XC skiing performance (R = 0.43 and 0.40, p <= 0.05). Although the importance of upper-body strength and lean mass to predict DP power production and the overall XC skiing performance declines with the performance duration in female XC skiers, the importance of V[Combining Dot Above]O2max shows an opposite relationship. PMID- 26817744 TI - Physical Performance of Brazilian Rugby Players From Different Age Categories and Competitive Levels. AB - Kobal, R, Nakamura, FY, Moraes, JE, Coelho, M, Kitamura, K, Cal Abad, CC, Pereira, LA, and Loturco, I. Physical performance of Brazilian rugby players from different age categories and competitive levels. J Strength Cond Res 30(9): 2433 2439, 2016-The aim of this study was to compare the anthropometric characteristics and physical capacities (vertical jumping, speed, agility, and endurance abilities) among different age categories of Brazilian rugby players from the same high-level club and to compare their respective data with those obtained from the national team players. Eighty-eight men Brazilian rugby players from 4 different age categories were divided into 4 different groups (i.e., under 15 [U-15], under-17 [U-17], under-19 [U-19], and professional senior team [PRO]) and a group composed of players from the Brazilian national team (NAT). Anthropometric measures (i.e., height and body mass), squat jump (SJ) and countermovement jump (CMJ) tests , 2 agility tests (change of direction [COD] and proagility), 40-m sprinting, and the Yo-Yo endurance test (level 1) were compared among the groups using an analysis of covariance (multivariable multivariate analysis of covariance) with the body mass as a covariate. The NAT group demonstrated significantly greater performances in all variables compared with the U-15, U-17, U-19, and PRO groups (p <= 0.05). Moreover, the PRO group demonstrated better performances in vertical jumping assessments (i.e., SJs and CMJs) and agility tests (i.e., COD and proagility) than the younger categories (p <= 0.05). Finally, except for the U-15 group, no significant differences were found between the young age-categories in sprint and endurance capacities. These findings show that, throughout the maturation process, rugby players improve their muscle power and agility abilities without presenting significant increases in endurance and sprinting capacities. Importantly, this does not hold true for players from the NAT group, who presented superior performance in all assessed physical variables (in comparison with the younger age and PRO categories). PMID- 26817745 TI - Increased Blood Lactate Level Deteriorates Running Economy in World Class Endurance Athletes. AB - Blood lactate accumulation is associated with development of muscle fatigue and negatively correlated to endurance performance. No research has quantified the effects of lactate presence at moderate levels of lactate accumulation. The purpose of this study was to test whether 2 moderate blood lactate concentration levels affect running economy (RE) when running at the individual lactate threshold (LT). Seven male world class endurance athletes with an average V[Combining Dot Above]O2max of 80.7 +/- 2.7 ml.kg.min or 5.8 +/- 0.5 L.min participated in this study. After the V[Combining Dot Above]O2max test, the subjects were resting or walking and in a random order tested for RE at their LT velocity when the blood lactate level reached either 3 mmol.L or 5 mmol.L. After a new 5-minute exercising period at maximal aerobic velocity, the crossover lactate value RE testing was performed. Running economy was significantly (p <= 0.05) deteriorated from 0.668 +/- 0.044 to 0.705 +/- 0.056 ml.kg.m or 5.5% (p <= 0.05) for blood lactate level of 3 mmol.L compared with 5 mmol.L, respectively. Increased lactate level from 3 to 5 mmol.L is thus accompanied by deteriorated RE at LT running velocity. The deteriorated RE at moderate levels of lactate concentration emphasizes the importance of avoiding intensities above LT in the early parts of a dominantly aerobic endurance competition. It also emphasizes the importance of a high V[Combining Dot Above]O2max for aerobic endurance athletes and may partly explain the V[Combining Dot Above]O2 slow component as impaired RE. PMID- 26817746 TI - How important is the eggshell as a source for initial acquisition of Salmonella in hatchling turtles? AB - How and when turtles first acquire gut microflora is largely speculative. In this study, the eggshell and hatching process were evaluated for their role in the initial acquisition of Salmonella, by red-eared slider turtles (Trachemys scripta elegans). First, we examined whether the eggshell is a viable substrate for bacterial persistence during incubation, and if internal egg components (i.e., albumen, yolk, and embryo) have detectable bacterial loads. Second, we experimentally manipulated Salmonella by treating eggs with combinations of Salmonella and gentamicin, an effective Gram-negative antibiotic. We found that the eggshell is a viable substrate for maintaining bacteria, as well as an effective barrier to Salmonella transmission as internal egg components were largely bacteria-free. Water samples collected 18 days post-hatch from individuals that were experimentally inoculated with a topical application of Salmonella as eggs had a higher prevalence of Salmonella than those from eggs inoculated with Salmonella but topically treated with gentamicin prior to hatching, control eggs, and eggs only treated with gentamicin, but by day 35 post hatch there were no detectable differences among the treatment groups. Though it can also act as a barrier that prevents the bacteria from infecting the embryo prior to hatching these findings suggest that the eggshell is a likely source of Salmonella infection in turtle hatchlings. PMID- 26817747 TI - A Tie2-driven BAC-TRAP transgenic line for in vivo endothelial gene profiling. AB - Recent technological innovations including bacterial artificial chromosome-based translating ribosome affinity purification (BAC-TRAP) have greatly facilitated analysis of cell type-specific gene expression in vivo, especially in the nervous system. To better study endothelial gene expression in vivo, we have generated a BAC-TRAP transgenic mouse line where the L10a ribosomal subunit is tagged with EGFP and placed under the control of the endothelium-specific Tie2 (Tek) promoter. We show that transgene expression in this line is widely, but specifically, detected in endothelial cells in several brain regions throughout pre- and postnatal development, as well as in other organs. We also show that this line results in highly significant enrichment of endothelium-specific mRNAs from brain tissues at different stages. This BAC-TRAP line therefore provides a useful genetic tool for in vivo endothelial gene profiling under various developmental, physiological, and pathological conditions. genesis 54:136-145, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26817748 TI - Mental health and clinical education. PMID- 26817749 TI - Developing interprofessional education: putting theory into practice. PMID- 26817752 TI - Borderline regression method versus borderline group method. PMID- 26817753 TI - More on standard setting. PMID- 26817754 TI - Standard setting is complex. PMID- 26817755 TI - Outcomes after cryoablation vs. radiofrequency in patients with paroxysmal atrial fibrillation: impact of pulmonary veins anatomy. AB - AIMS: Pulmonary vein isolation is the mainstay of treatment in catheter ablation of paroxysmal atrial fibrillation (AF). Cryoballoon ablation has been introduced more recently than radiofrequency ablation, the standard technique in most centres. Pulmonary veins frequently display anatomical variants, which may compromise the results of cryoballoon ablation. We aimed to evaluate the mid-term outcomes of cryoballoon ablation in an unselected population with paroxysmal AF from an anatomical viewpoint. METHODS AND RESULTS: Consecutive patients with paroxysmal AF who underwent a first procedure of cryoballoon ablation or radiofrequency were enrolled in this single-centre study. All patients underwent systematic standardized follow-up. Comparisons between radiofrequency and cryoballoon ablation (Arctic FrontTM or Arctic Front AdvanceTM) were performed regarding safety and efficacy endpoints, according to pulmonary vein (PV) anatomical variants. A total of 687 patients were enrolled (376 radiofrequency and 311 cryoballoon ablation). Baseline characteristics and distribution of PV anatomical variants were generally similar in the groups. After a mean follow-up of 14 +/- 8 months, there was no difference in the incidence of relapse (17.0% cryoballoon ablation vs. 14.1% radiofrequency, P = 0.25). We observed no interaction of PV anatomical variants on mid-term procedural success. CONCLUSION: Our findings suggest that mid-term outcomes of cryoballoon ablation for paroxysmal AF ablation are similar to those of radiofrequency, regardless of PV anatomy. The presence of anatomical variants of PVs should not discourage the referral of patients with paroxysmal AF for cryoballoon ablation. PMID- 26817756 TI - Evolutionarily Stable Strategies for Fecundity and Swimming Speed of Fish. AB - Many pelagic fish species have a life history that involves producing a large number of small eggs. This is the result of a trade-off between fecundity and larval survival probability. There are also trade-offs involving other traits, such as larval swimming speed. Swimming faster increases the average food encounter rate but also increases the metabolic cost. Here we introduce an evolutionary model comprising fecundity and swimming speed as heritable traits. We show that there can be two evolutionary stable strategies. In environments where there is little noise in the food encounter rate, the stable strategy is a low-fecundity strategy with a swimming speed that minimises the mean time taken to reach reproductive maturity. However, in noisy environments, for example where the prey distribution is patchy or the water is turbulent, strategies that optimise mean outcomes are often outperformed by strategies that increase inter individual variance. We show that, when larval growth rates are unpredictable, a high-fecundity strategy is evolutionarily stable. In a population following this strategy, the swimming speed is higher than would be anticipated by maximising the mean growth rate. PMID- 26817757 TI - Evolution of Dispersal with Starvation Measure and Coexistence. AB - Many biological species increase their dispersal rate if starvation starts. To model such a behavior, we need to understand how organisms measure starvation and response to it. In this paper, we compare three different ways of measuring starvation by applying them to starvation-driven diffusion. The evolutional selection and coexistence of such starvation measures are studied within the context of Lotka-Volterra-type competition model of two species. We will see that, if species have different starvation measures and different motility functions, both the coexistence and selection are possible. PMID- 26817758 TI - Influence of beta-blocker therapy on aortic blood flow in patients with bicuspid aortic valve. AB - In patients with bicuspid aortic valve (BAV), beta-blockers (BB) are assumed to slow ascending aorta (AAo) dilation by reducing wall shear stress (WSS) on the aneurysmal segment. The aim of this study was to assess differences in AAo peak velocity and WSS in BAV patients with and without BB therapy. BAV patients receiving BB (BB+, n = 30, age: 47 +/- 11 years) or not on BB (BB-, n = 30, age: 46 +/- 13 years) and healthy controls (n = 15, age: 43 +/- 11 years) underwent 4D flow MRI for the assessment of in vivo aortic 3D blood flow. Peak systolic velocities and 3D WSS were calculated at the anterior and posterior walls of the AAo. Both patient groups had higher maximum and mean WSS relative to the control group (p = 0.001 to p = 0.04). WSS was not reduced in the BB+ group compared to BB- patients in the anterior AAo (maximum: 1.49 +/- 0.47 vs. 1.38 +/- 0.49 N/m(2), p = 0.99, mean: 0.76 +/- 0.2 vs. 0.74 +/- 0.18 N/m(2), p = 1.00) or posterior AAo (maximum: 1.45 +/- 0.42 vs. 1.39 +/- 0.58 N/m(2), p = 1.00; mean: 0.65 +/- 0.16 vs. 0.63 +/- 0.16 N/m(2), p = 1.00). AAo peak velocity was elevated in patients compared to controls (p < 0.01) but similar for BB+ and BB- groups (p = 0.42). Linear models identified significant relationships between aortic stenosis severity and increased maximum WSS (beta = 0.186, p = 0.007) and between diameter at the sinus of Valsalva and reduced mean WSS (beta = -0.151, p = 0.045). Peak velocity and systolic WSS were similar for BAV patients irrespective of BB therapy. Further prospective studies are needed to investigate the impact of dosage and duration of BB therapy on aortic hemodynamics and development of aortopathy. PMID- 26817759 TI - Novel Software-Assisted Hemodynamic Evaluation of Pelvic Flow During Chemoperfusion of Pelvic Arteries for Bladder Cancer: Double- Versus Single Balloon Technique. AB - PURPOSE: Approximately 83 % of patients with bladder cancer have achieved a complete response after undergoing a novel bladder preservation therapy involving balloon-occluded intra-arterial infusion chemotherapy (BOAI) using a four-lumen double-balloon catheter, known as the Osaka Medical College regimen. This study aimed to show the quantitative difference in hemodynamics of the bladder arteries using syngo iFlow (Siemens Healthcare, Erlangen, Germany), which provides an automatic tool for quantitative blood flow analysis between double BOAI (D-BOAI) and conventional single BOAI (S-BOAI). MATERIALS AND METHODS: Fifty patients were included. The catheters were introduced into both posterior trunks of the internal iliac arteries via contralateral femoral artery access. A side hole between the distal and proximal balloons was placed at the origin of each bladder artery to allow clear visualization of angiographic flow of the injected agent into the urinary bladder. Digital subtraction angiography was used during analysis with the syngo iFlow to evaluate the hemodynamics of the contrast medium in the pelvic arteries during BOAI. The comparative change in the amount of contrast medium in the bladder arteries between D-BOAI and S-BOAI was assessed using syngo iFlow. RESULTS: One-hundred pelvic sides were analyzed. The amount of contrast medium in the bladder arteries using D-BOAI was more than twice that using S-BOAI (right, 3.03-fold; left, 2.81-fold). CONCLUSION: The amount of contrast medium in the bladder arteries using D-BOAI was higher than that using conventional S-BOAI. This may increase the anticancer drug concentration in the affected bladder, leading to a good clinical response. PMID- 26817760 TI - Long-Term Efficacy of Percutaneous Internal Plastic Stent Placement for Non anastomotic Biliary Stenosis After Liver Transplantation. AB - PURPOSE: We aimed to evaluate the long-term efficacy of percutaneous management of non-anastomotic biliary stenosis after liver transplantation, using plastic internal biliary stents. MATERIALS AND METHODS: This study included 35 cases (28 men, 7 women; mean age: 52.09 +/- 8.13 years, range 34-68) in 33 patients who needed repeated interventional procedures because of biliary strictures. After classification of the biliary strictures, we inserted percutaneous biliary plastic stents through the T-tube or percutaneous transhepatic biliary drainage tracts. Stents were exchanged according to percutaneous methods at regular 2- to 6-month intervals. The stents were removed if the condition improved, as observed on cholangiogram as well as based on clinical findings. The median patient follow up period after initial diagnosis and treatment was 6.04 years (range 0.29-9.95 years). We assessed treatment success rate and patient and graft survival times. RESULTS: During the follow-up period, 14 patients (14/33, 42.42 %) were successfully treated and were tube-free. The median tube-free time, time without a stent, was 4.13 years (range 1.00-9.01). In contrast, internal plastic stents remained in 9 patients (9/33, 27.27 %) until the last follow-up. These patients had acceptable hepatic function. Among the remaining 10 patients, 3 (3/33, 9.09 %) were lost to regular follow-up and the other 7 (7/33, 21.21 %) patients died. The overall graft loss rate was 20.0 % (7/35). The median time from initial treatment to graft loss was 1.84 years (range 0.42-4.25). CONCLUSIONS: Percutaneous plastic stents placement is technically feasible and clinically useful in patients with multiple biliary stenoses following liver transplantation. PMID- 26817761 TI - Optimising Pulmonary Microwave Ablation Using Trans-Scapular Access and Continuous Temperature Monitoring. PMID- 26817763 TI - Fusion Method for Solubility and Dissolution Rate Enhancement of Ibuprofen Using Block Copolymer Poloxamer 407. AB - Aim of current research was to prepare ibuprofen-poloxamer 407 binary mixtures using fusion method and characterize them for their physicochemical and performance properties. Binary mixtures of ibuprofen and poloxamer were prepared in three different ratios (1:0.25, 1:0.5, and 1:0.75, respectively) using a water jacketed high shear mixer. In vitro dissolution and saturation solubility studies were carried out for the drug, physical mixtures, and formulations for all ratios in de-ionized water, 0.1 N HCl (pH = 1.2), and phosphate buffer (pH = 7.2). Thermal and physical characterization of samples was done using modulated differential scanning calorimetry (mDSC), X-ray powder diffraction (XRD), and infrared spectroscopy (FTIR). Flow properties were evaluated using a powder rheometer. Maximum solubility enhancement was seen in acidic media for fused formulations where the ratio 1:0.75 had 18-fold increase. In vitro dissolution studies showed dissolution rate enhancement for physical mixtures and the formulations in all three media. The most pronounced effect was seen for formulation (1:0.75) in acidic media where the cumulative drug release was 58.27% while for drug, it was 3.67%. Model independent statistical methods and ANOVA based methods were used to check the significance of difference in the dissolution profiles. Thermograms from mDSC showed a characteristic peak for all formulations with Tpeak of around 45 degrees C which suggested formation of a eutectic mixture. XRD data displayed that crystalline nature of ibuprofen was intact in the formulations. This work shows the effect of eutectic formation and micellar solubilization between ibuprofen and poloxamer at the given ratios on its solubility and dissolution rate enhancement. PMID- 26817762 TI - Wrist motion analysis in scaphoid nonunion. AB - INTRODUCTION: The motion of human wrist is a complex and multidirectional process. The aim of this study was to develop a reliable and practicable method to measure motion impairment of the wrist in patients who incurred a scaphoid nonunion. A scaphoid nonunion in computed tomography as well as the consent in this study was required. METHODS: A total of nine patients with unilateral scaphoid nonunion accomplished maximal circumferential wrist movements. The wrist movements were measured with an electrogoniometer (Biometrics Ltd.). To quantify maximal wrist motion we constructed the maximal boundaries of the wrist motion from angular plots in flexion-extension (FE) and radio-ulnar deviation (RUD). We calculated the area of the circumduction envelope, the ranges of motion in FE and RUD and the main axis in wrist motion (dart-throwin-motion). The collected data were reconstructed with a custom-made MatLab program. We compared the impaired with the unimpaired side of each patient and analyzed with student's t test. RESULTS: A scaphoid nonunion significantly reduced motion ranges in flexion/extension but not in ulnar and radial deviation. The overall mobility as quantified by the area of the circumduction envelope, decreased significantly. The circumduction boundaries of the wrists showed a kidney-shaped configuration with an oblique axis from radial/extension to ulnar/flexion. CONCLUSION: Our results demonstrate that scaphoid nonunion without pain has motion deficits and may be poorly quantified with conventional manual goniometers. PMID- 26817764 TI - Formulation and Characterization of Bovine Serum Albumin-Loaded Niosome. AB - Niosomal vesicle, as a unique novel drug delivery system, is synthesized by non ionic surfactants. Both hydrophilic and lipophilic drugs and also biomacromolecular agents, such as peptides and proteins can be encapsulated in this vesicular particle. Regarding polypeptide-based component loading, and delivery potential of the niosome, some valuable studies have been conducted in recent years. However, exploring the full potential of this approach requires fine tuned optimization and characterization approaches. Therefore, this study was conducted to achieve the following two goals. First, formulation and optimization of bovine serum albumin (BSA) load and release behavior as a function of cholesterol (CH) to sorbitan monostearate (Span 60) molar ratio. Second, investigating a cost- and time-effective polypeptide detecting method via methyl orange (MO) dye. To this aim, BSA-loaded niosomes were prepared by reversed-phase evaporation technique. The effect of CH to Sorbitan monostearate (Span 60) molar ratio on noisome entrapment efficiency (EE%) and release profile of BSA was studied using a ultraviolet (UV) spectrophotometer technique (NanoDrop 2000/2000c).Niosome with a 60% CH content showed the highest BSA EE% and release behavior. Then, BSA was dyed using MO in an acidic solution and used in BSA niosome formulation. The MO-colored protein, loaded into the vesicles, was successfully assessed by an inverted light microscope, in order to observe the protein location in the vesicle. The results obtained in this study can be useful for various applications in different fields, including pharmaceutical, cosmetics, and drug delivery in biomedical and tissue engineering. PMID- 26817765 TI - Corridors restore animal-mediated pollination in fragmented tropical forest landscapes. AB - Tropical biodiversity and associated ecosystem functions have become heavily eroded through habitat loss. Animal-mediated pollination is required in more than 94% of higher tropical plant species and 75% of the world's leading food crops, but it remains unclear if corridors avert deforestation-driven pollination breakdown in fragmented tropical landscapes. Here, we used manipulative resource experiments and field observations to show that corridors functionally connect neotropical forest fragments for forest-associated hummingbirds and increase pollen transfer. Further, corridors boosted forest-associated pollinator availability in fragments by 14.3 times compared with unconnected equivalents, increasing overall pollination success. Plants in patches without corridors showed pollination rates equal to bagged control flowers, indicating pollination failure in isolated fragments. This indicates, for the first time, that corridors benefit tropical forest ecosystems beyond boosting local species richness, by functionally connecting mutualistic network partners. We conclude that small scale adjustments to landscape configuration safeguard native pollinators and associated pollination services in tropical forest landscapes. PMID- 26817766 TI - The evolution of sensitive periods in a model of incremental development. AB - Sensitive periods, in which experience shapes phenotypic development to a larger extent than other periods, are widespread in nature. Despite a recent focus on neural-physiological explanation, few formal models have examined the evolutionary selection pressures that result in developmental mechanisms that produce sensitive periods. Here, we present such a model. We model development as a specialization process during which individuals incrementally adapt to local environmental conditions, while receiving a constant stream of cost-free, imperfect cues to the environmental state. We compute optimal developmental programmes across a range of ecological conditions and use these programmes to simulate developmental trajectories and obtain distributions of mature phenotypes. We highlight four main results. First, matching the empirical record, sensitive periods often result from experience or from a combination of age and experience, but rarely from age alone. Second, individual differences in sensitive periods emerge as a result of stochasticity in cues: individuals who obtain more consistent cue sets lose their plasticity at faster rates. Third, in some cases, experience shapes phenotypes only at a later life stage (lagged effects). Fourth, individuals might perseverate along developmental trajectories despite accumulating evidence suggesting the alternate trajectory is more likely to match the ecology. PMID- 26817767 TI - Global patterns in threats to vertebrates by biological invasions. AB - Biological invasions as drivers of biodiversity loss have recently been challenged. Fundamentally, we must know where species that are threatened by invasive alien species (IAS) live, and the degree to which they are threatened. We report the first study linking 1372 vertebrates threatened by more than 200 IAS from the completely revised Global Invasive Species Database. New maps of the vulnerability of threatened vertebrates to IAS permit assessments of whether IAS have a major influence on biodiversity, and if so, which taxonomic groups are threatened and where they are threatened. We found that centres of IAS-threatened vertebrates are concentrated in the Americas, India, Indonesia, Australia and New Zealand. The areas in which IAS-threatened species are located do not fully match the current hotspots of invasions, or the current hotspots of threatened species. The relative importance of biological invasions as drivers of biodiversity loss clearly varies across regions and taxa, and changes over time, with mammals from India, Indonesia, Australia and Europe are increasingly being threatened by IAS. The chytrid fungus primarily threatens amphibians, whereas invasive mammals primarily threaten other vertebrates. The differences in IAS threats between regions and taxa can help efficiently target IAS, which is essential for achieving the Strategic Plan 2020 of the Convention on Biological Diversity. PMID- 26817768 TI - Multiple rod-cone and cone-rod photoreceptor transmutations in snakes: evidence from visual opsin gene expression. AB - In 1934, Gordon Walls forwarded his radical theory of retinal photoreceptor 'transmutation'. This proposed that rods and cones used for scotopic and photopic vision, respectively, were not fixed but could evolve into each other via a series of morphologically distinguishable intermediates. Walls' prime evidence came from series of diurnal and nocturnal geckos and snakes that appeared to have pure-cone or pure-rod retinas (in forms that Walls believed evolved from ancestors with the reverse complement) or which possessed intermediate photoreceptor cells. Walls was limited in testing his theory because the precise identity of visual pigments present in photoreceptors was then unknown. Subsequent molecular research has hitherto neglected this topic but presents new opportunities. We identify three visual opsin genes, rh1, sws1 and lws, in retinal mRNA of an ecologically and taxonomically diverse sample of snakes central to Walls' theory. We conclude that photoreceptors with superficially rod- or cone-like morphology are not limited to containing scotopic or photopic opsins, respectively. Walls' theory is essentially correct, and more research is needed to identify the patterns, processes and functional implications of transmutation. Future research will help to clarify the fundamental properties and physiology of photoreceptors adapted to function in different light levels. PMID- 26817769 TI - A gene associated with social immunity in the burying beetle Nicrophorus vespilloides. AB - Some group-living species exhibit social immunity, where the immune response of one individual can protect others in the group from infection. In burying beetles, this is part of parental care. Larvae feed on vertebrate carcasses which their parents smear with exudates that inhibit microbial growth. We have sequenced the transcriptome of the burying beetle Nicrophorus vespilloides and identified six genes that encode lysozymes-a type of antimicrobial enzyme that has previously been implicated in social immunity in burying beetles. When females start breeding and producing antimicrobial anal exudates, we found that the expression of one of these genes was increased by approximately 1000 times to become one of the most abundant transcripts in the transcriptome. Females varied considerably in the antimicrobial properties of their anal exudates, and this was strongly correlated with the expression of this lysozyme. We conclude that we have likely identified a gene encoding a key effector molecule in social immunity and that it was recruited during evolution from a function in personal immunity. PMID- 26817770 TI - The effect of activation level on muscle function during locomotion: are optimal lengths and velocities always used? AB - Skeletal muscle exhibits broad functional diversity, despite its inherent length and velocity constraints. The observed variation in morphology and physiology is assumed to have evolved to allow muscle to operate at its optimal length and velocity during locomotion. Here, we used the variation in optimum lengths and velocities that occurs with muscle activation level to experimentally test this assumption. Muscle ergometry and sonomicrometry were used to characterize force length and power-velocity relationships, and in vivo operating lengths and velocities, at a range of activation levels. Operating lengths and velocities were mapped onto activation level specific force-length and power-velocity relationships to determine whether they tracked changing optima. Operating velocities decreased in line with decreased optimal velocities, suggesting that optimal velocities are always used. However, operating lengths did not change with changing optima. At high activation levels, fibres used an optimal range of lengths. However, at lower activation levels, fibres appeared to operate on the ascending limb of sub-maximally activated force-length relationships. This suggests that optimal lengths are only used when demand is greatest. This study provides the first mapping of operating lengths to activation level-specific optima, and as such, provides insight into our assumptions about the factors that determine muscle performance during locomotion. PMID- 26817771 TI - The Achilles' heel hypothesis: misinformed keystone individuals impair collective learning and reduce group success. AB - Many animal societies rely on highly influential keystone individuals for proper functioning. When information quality is important for group success, such keystone individuals have the potential to diminish group performance if they possess inaccurate information. Here, we test whether information quality (accurate or inaccurate) influences collective outcomes when keystone individuals are the first to acquire it. We trained keystone or generic individuals to attack or avoid novel stimuli and implanted these trained individuals within groups of naive colony-mates. We subsequently tracked how quickly groups learned about their environment in situations that matched (accurate information) or mismatched (inaccurate information) the training of the trained individual. We found that colonies with just one accurately informed individual were quicker to learn to attack a novel prey stimulus than colonies with no informed individuals. However, this effect was no more pronounced when the informed individual was a keystone individual. In contrast, keystones with inaccurate information had larger effects than generic individuals with identical information: groups containing keystones with inaccurate information took longer to learn to attack/avoid prey/predator stimuli and gained less weight than groups harbouring generic individuals with identical information. Our results convey that misinformed keystone individuals can become points of vulnerability for their societies. PMID- 26817772 TI - Untangling the early diversification of eukaryotes: a phylogenomic study of the evolutionary origins of Centrohelida, Haptophyta and Cryptista. AB - Assembling the global eukaryotic tree of life has long been a major effort of Biology. In recent years, pushed by the new availability of genome-scale data for microbial eukaryotes, it has become possible to revisit many evolutionary enigmas. However, some of the most ancient nodes, which are essential for inferring a stable tree, have remained highly controversial. Among other reasons, the lack of adequate genomic datasets for key taxa has prevented the robust reconstruction of early diversification events. In this context, the centrohelid heliozoans are particularly relevant for reconstructing the tree of eukaryotes because they represent one of the last substantial groups that was missing large and diverse genomic data. Here, we filled this gap by sequencing high-quality transcriptomes for four centrohelid lineages, each corresponding to a different family. Combining these new data with a broad eukaryotic sampling, we produced a gene-rich taxon-rich phylogenomic dataset that enabled us to refine the structure of the tree. Specifically, we show that (i) centrohelids relate to haptophytes, confirming Haptista; (ii) Haptista relates to SAR; (iii) Cryptista share strong affinity with Archaeplastida; and (iv) Haptista + SAR is sister to Cryptista + Archaeplastida. The implications of this topology are discussed in the broader context of plastid evolution. PMID- 26817773 TI - Effective number of breeders, effective population size and their relationship with census size in an iteroparous species, Salvelinus fontinalis. AB - The relationship between the effective number of breeders (Nb) and the generational effective size (Ne) has rarely been examined empirically in species with overlapping generations and iteroparity. Based on a suite of 11 microsatellite markers, we examine the relationship between Nb, Ne and census population size (Nc) in 14 brook trout (Salvelinus fontinalis) populations inhabiting 12 small streams in Nova Scotia and sampled at least twice between 2009 and 2015. Unbiased estimates of Nb obtained with individuals of a single cohort, adjusted on the basis of age at first maturation (alpha) and adult lifespan (AL), were from 1.66 to 0.24 times the average estimates of Ne obtained with random samples of individuals of mixed ages (i.e. [Formula: see text]). In turn, these differences led to adjusted Ne estimates that were from nearly five to 0.7 times the estimates derived from mixed-aged individuals. These differences translate into the same range of variation in the ratio of effective to census population size [Formula: see text] within populations. Adopting [Formula: see text] as the more precise and unbiased estimates, we found that these brook trout populations differ markedly in their effective to census population sizes (range approx. 0.3 to approx. 0.01). Using AgeNe, we then showed that the variance in reproductive success or reproductive skew varied among populations by a factor of 40, from Vk/k ~ 5 to 200. These results suggest wide differences in population dynamics, probably resulting from differences in productivity affecting the intensity of competition for access to mates or redds, and thus reproductive skew. Understanding the relationship between Ne, Nb and Nc, and how these relate to population dynamics and fluctuations in population size, are important for the design of robust conservation strategies in small populations with overlapping generations and iteroparity. PMID- 26817774 TI - Quantifying drivers of population dynamics for a migratory bird throughout the annual cycle. AB - Worldwide, migratory species are undergoing rapid declines but understanding the factors driving these declines is hindered by missing information about migratory connectivity and the lack of data to quantify environmental processes across the annual cycle. Here, we combined range-wide information about migratory connectivity with global remote-sensing data to quantify the relative importance of breeding and non-breeding environmental processes to persistent long-term population declines of a migratory songbird, the wood thrush (Hylocichla mustelina). Consistent with theoretical predictions about population limitation of migratory birds, our results suggest that habitat loss and climate have contributed to the observed declines in wood thrush breeding abundance, yet the relative importance of breeding versus non-breeding factors is population specific. For example, high-abundance core breeding populations appear to be more limited by habitat loss, whereas low-abundance, peripheral populations appear to be limited by climate-driven seasonal interactions. Further, our analysis indicates that the relative impact of breeding habitat loss is at least three to six times greater than the impact of equivalent non-breeding habitat loss and therefore the steepest regional declines have likely been driven by the loss of breeding habitat. These results underscore the need for population-specific conservation strategies implemented throughout the annual cycle to reverse long term declines. PMID- 26817775 TI - Local adaptation in transgenerational responses to predators. AB - Environmental signals can induce phenotypic changes that span multiple generations. Along with phenotypic responses that occur during development (i.e. 'within-generation' plasticity), such 'transgenerational plasticity' (TGP) has been documented in a diverse array of taxa spanning many environmental perturbations. New theory predicts that temporal stability is a key driver of the evolution of TGP. We tested this prediction using natural populations of zooplankton from lakes in Connecticut that span a large gradient in the temporal dynamics of predator-induced mortality. We reared more than 120 clones of Daphnia ambigua from nine lakes for multiple generations in the presence/absence of predator cues. We found that temporal variation in mortality selects for within generation plasticity while consistently strong (or weak) mortality selects for increased TGP. Such results provide us the first evidence for local adaptation in TGP and argue that divergent ecological conditions select for phenotypic responses within and across generations. PMID- 26817776 TI - Virtual endocasts of Eocene Paramys (Paramyinae): oldest endocranial record for Rodentia and early brain evolution in Euarchontoglires. AB - Understanding the pattern of brain evolution in early rodents is central to reconstructing the ancestral condition for Glires, and for other members of Euarchontoglires including Primates. We describe the oldest virtual endocasts known for fossil rodents, which pertain to Paramys copei (Early Eocene) and Paramys delicatus (Middle Eocene). Both specimens of Paramys have larger olfactory bulbs and smaller paraflocculi relative to total endocranial volume than later occurring rodents, which may be primitive traits for Rodentia. The encephalization quotients (EQs) of Pa. copei and Pa. delicatus are higher than that of later occurring (Oligocene) Ischyromys typus, which contradicts the hypothesis that EQ increases through time in all mammalian orders. However, both species of Paramys have a lower relative neocortical surface area than later rodents, suggesting neocorticalization occurred through time in this Order, although to a lesser degree than in Primates. Paramys has a higher EQ but a lower neocortical ratio than any stem primate. This result contrasts with the idea that primates were always exceptional in their degree of overall encephalization and shows that relative brain size and neocortical surface area do not necessarily covary through time. As such, these data contradict assumptions made about the pattern of brain evolution in Euarchontoglires. PMID- 26817777 TI - Diabolical survival in Death Valley: recent pupfish colonization, gene flow and genetic assimilation in the smallest species range on earth. AB - One of the most endangered vertebrates, the Devils Hole pupfish Cyprinodon diabolis, survives in a nearly impossible environment: a narrow subterranean fissure in the hottest desert on earth, Death Valley. This species became a conservation icon after a landmark 1976 US Supreme Court case affirming federal groundwater rights to its unique habitat. However, one outstanding question about this species remains unresolved: how long has diabolis persisted in this hellish environment? We used next-generation sequencing of over 13 000 loci to infer the demographic history of pupfishes in Death Valley. Instead of relicts isolated 2-3 Myr ago throughout repeated flooding of the entire region by inland seas as currently believed, we present evidence for frequent gene flow among Death Valley pupfish species and divergence after the most recent flooding 13 kyr ago. We estimate that Devils Hole was colonized by pupfish between 105 and 830 years ago, followed by genetic assimilation of pelvic fin loss and recent gene flow into neighbouring spring systems. Our results provide a new perspective on an iconic endangered species using the latest population genomic methods and support an emerging consensus that timescales for speciation are overestimated in many groups of rapidly evolving species. PMID- 26817778 TI - Asymmetric competition causes multimodal size distributions in spatially structured populations. AB - Plant sizes within populations often exhibit multimodal distributions, even when all individuals are the same age and have experienced identical conditions. To establish the causes of this, we created an individual-based model simulating the growth of trees in a spatially explicit framework, which was parametrized using data from a long-term study of forest stands in New Zealand. First, we demonstrate that asymmetric resource competition is a necessary condition for the formation of multimodal size distributions within cohorts. By contrast, the legacy of small-scale clustering during recruitment is transient and quickly overwhelmed by density-dependent mortality. Complex multi-layered size distributions are generated when established individuals are restricted in the spatial domain within which they can capture resources. The number of modes reveals the effective number of direct competitors, while the separation and spread of modes are influenced by distances among established individuals. Asymmetric competition within local neighbourhoods can therefore generate a range of complex size distributions within even-aged cohorts. PMID- 26817779 TI - Morphology predicts species' functional roles and their degree of specialization in plant-frugivore interactions. AB - Species' functional roles in key ecosystem processes such as predation, pollination or seed dispersal are determined by the resource use of consumer species. An interaction between resource and consumer species usually requires trait matching (e.g. a congruence in the morphologies of interaction partners). Species' morphology should therefore determine species' functional roles in ecological processes mediated by mutualistic or antagonistic interactions. We tested this assumption for Neotropical plant-bird mutualisms. We used a new analytical framework that assesses a species's functional role based on the analysis of the traits of its interaction partners in a multidimensional trait space. We employed this framework to test (i) whether there is correspondence between the morphology of bird species and their functional roles and (ii) whether morphologically specialized birds fulfil specialized functional roles. We found that morphological differences between bird species reflected their functional differences: (i) bird species with different morphologies foraged on distinct sets of plant species and (ii) morphologically distinct bird species fulfilled specialized functional roles. These findings encourage further assessments of species' functional roles through the analysis of their interaction partners, and the proposed analytical framework facilitates a wide range of novel analyses for network and community ecology. PMID- 26817780 TI - The influence of complex and threatening environments in early life on brain size and behaviour. AB - The ways in which challenging environments during development shape the brain and behaviour are increasingly being addressed. To date, studies typically consider only single variables, but the real world is more complex. Many factors simultaneously affect the brain and behaviour, and whether these work independently or interact remains untested. To address this, zebrafish (Danio rerio) were reared in a two-by-two design in housing that varied in structural complexity and/or exposure to a stressor. Fish experiencing both complexity (enrichment objects changed over time) and mild stress (daily net chasing) exhibited enhanced learning and were less anxious when tested as juveniles (between 77 and 90 days). Adults tested (aged 1 year) were also less anxious even though fish were kept in standard housing after three months of age (i.e. no chasing or enrichment). Volumetric measures of the brain using magnetic resonance imaging (MRI) showed that complexity alone generated fish with a larger brain, but this increase in size was not seen in fish that experienced both complexity and chasing, or chasing alone. The results highlight the importance of looking at multiple variables simultaneously, and reveal differential effects of complexity and stressful experiences during development of the brain and behaviour. PMID- 26817781 TI - A national point prevalence study on healthcare-associated infections and antimicrobial use in Austria. AB - BACKGROUND: The first point prevalence survey performed in Austria had the aim to assess the magnitude of healthcare-associated infections and antimicrobials use in the country. METHODS: A multicentre study was carried out from May until June 2012 in nine acute care hospitals with a mean bed number of 620. Data from 4321 patients' clinical charts were reviewed. RESULTS: The overall healthcare associated infections prevalence was 6.2% (268/4321) with the highest rate in intensive care departments (20.9%; 49/234). In medical and surgical departments the healthcare-associated infections prevalence was 5.4% (95/1745) and 6.6% (105/1586), respectively. The most frequent healthcare-associated infections were: urinary tract infections (21.3%; 61/287), pneumonia (20.6%; 59/287) and surgical site infections (17.4%; 50/287). The most common isolated microorganisms were: Escherichia coli (14.8%; 26/176), Enterococcus species (13.1%; 23/176) and Pseudomonas aeruginosa (11.4%; 20/176). Thirty-three per cent (1425/4321) of the patients received antimicrobials because of community-acquired infections treatment (14.2%; 615/4321), healthcare-associated infections treatment (6.4%; 278/4321), and surgical (8.2%; 354/4321) and medical prophylaxis (3.2%; 138/4321). Surgical prophylaxis was the indication for 22.0% (394/1792) of the overall prescriptions and was prolonged for more than 1 day in 77.2% (304/394) of the cases. CONCLUSION: The national Austrian survey proved the feasibility of a nation-wide network of surveillance of both healthcare-associated infections and antimicrobial use that will be repeated in the future. Healthcare-associated infections and antimicrobial use have been confirmed to be a grave health problem. The excessive prolongation of perioperative prophylaxis in Austria needs to be limited. PMID- 26817782 TI - Comprehensive Health Risk Management after the Fukushima Nuclear Power Plant Accident. AB - Five years have passed since the Great East Japan Earthquake and the subsequent Fukushima Daiichi Nuclear Power Plant accident on 11 March 2011. Countermeasures aimed at human protection during the emergency period, including evacuation, sheltering and control of the food chain were implemented in a timely manner by the Japanese Government. However, there is an apparent need for improvement, especially in the areas of nuclear safety and protection, and also in the management of radiation health risk during and even after the accident. Continuous monitoring and characterisation of the levels of radioactivity in the environment and foods in Fukushima are now essential for obtaining informed consent to the decisions on living in the radio-contaminated areas and also on returning back to the evacuated areas once re-entry is allowed; it is also important to carry out a realistic assessment of the radiation doses on the basis of measurements. Until now, various types of radiation health risk management projects and research have been implemented in Fukushima, among which the Fukushima Health Management Survey is the largest health monitoring project. It includes the Basic Survey for the estimation of external radiation doses received during the first 4 months after the accident and four detailed surveys: thyroid ultrasound examination, comprehensive health check-up, mental health and lifestyle survey, and survey on pregnant women and nursing mothers, with the aim to prospectively take care of the health of all the residents of Fukushima Prefecture for a long time. In particular, among evacuees of the Fukushima Nuclear Power Plant accident, concern about radiation risk is associated with psychological stresses. Here, ongoing health risk management will be reviewed, focusing on the difficult challenge of post-disaster recovery and resilience in Fukushima. PMID- 26817784 TI - Interactions and exchange of CO2 and H2O in coals: an investigation by low-field NMR relaxation. AB - The mechanisms by which CO2 and water interact in coal remain unclear and these are key questions for understanding ECBM processes and defining the long-term behaviour of injected CO2. In our experiments, we injected helium/CO2 to displace water in eight water-saturated samples. We used low-field NMR relaxation to investigate CO2 and water interactions in these coals across a variety of time scales. The injection of helium did not change the T2 spectra of the coals. In contrast, the T2 spectra peaks of micro-capillary water gradually decreased and those of macro-capillary and bulk water increased with time after the injection of CO2. We assume that the CO2 diffuses through and/or dissolves into the capillary water to access the coal matrix interior, which promotes desorption of water molecules from the surfaces of coal micropores and mesopores. The replaced water mass is mainly related to the Langmuir adsorption volume of CO2 and increases as the CO2 adsorption capacity increases. Other factors, such as mineral composition, temperature and pressure, also influence the effective exchange between water and CO2. Finally, we built a quantified model to evaluate the efficiency of water replacement by CO2 injection with respect to temperature and pressure. PMID- 26817783 TI - Preadmission use of renin-angiotensin blockers and rupture of abdominal aortic aneurysm: a nationwide, population-based study. AB - PURPOSE: Rupture of abdominal aortic aneurysms (rAAA) is associated with high mortality. Use of angiotensin converting enzyme inhibitors (ACE-inhibitors) and angiotensin receptor blockers (ARBs) has been suggested to reduce the risk of rAAA. This nationwide, combined case-control and follow-up study aims to examine the possible impact of preadmission renin-angiotensin system blockade on the risk of rAAA and case fatality following rAAA. METHODS: Using Danish healthcare registries, a combined case-control and follow-up study was conducted among all patients with a first-time hospital admission for rAAA and AAA controls without rupture in Denmark from 1996 to 2012. Individual-level data were obtained on preadmission drug use, comorbidity, socioeconomic factors, healthcare services use, and death. RESULTS: The adjusted age-matched and sex-matched odds ratios (adj. OR) were 0.96 (95% confidence interval (CI): 0.85; 1.07) for rAAA for current ACE-inhibitor users and 0.93 (95%CI: 0.79; 1.09) for current ARB users compared with never users. Propensity score-matched analyses yielded similar results for current ACE-inhibitor users (adj. OR: 1.02, 95%CI: 0.88; 1.19) and current ARB users (adj. OR: 1.02, 95%CI: 0.83; 1.26). The total 30-day mortality rate after hospital admission was 61.0% in current ACE-inhibitor users compared with 59.4% in non-ACE-inhibitor users (adjusted mortality rate ratio (adj. MRR) 1.06, 95%CI: 0.94; 1.20) and 58.6% in current ARB users compared with 59.9% in non-ARB users (adj. MRR: 0.96, 95%CI: 0.82; 1.14). CONCLUSION: Use of renin angiotensin system blockade was not associated with a lower risk of rAAA or lower case fatality following rAAA. PMID- 26817786 TI - Ligand selectivity in tachykinin and natalisin neuropeptidergic systems of the honey bee parasitic mite Varroa destructor. AB - The varroa mite, Varroa destructor, is a devastating ectoparasite of the honey bees Apis mellifera and A. cerana. Control of these mites in beehives is a challenge in part due to the lack of toxic agents that are specific to mites and not to the host honey bee. In searching for a specific toxic target of varroa mites, we investigated two closely related neuropeptidergic systems, tachykinin related peptide (TRP) and natalisin (NTL), and their respective receptors. Honey bees lack both NTL and the NTL receptor in their genome sequences, providing the rationale for investigating these receptors to understand their specificities to various ligands. We characterized the receptors for NTL and TRP of V. destructor (VdNTL-R and VdTRP-R, respectively) and for TRP of A. mellifera (AmTRP-R) in a heterologous reporter assay system to determine the activities of various ligands including TRP/NTL peptides and peptidomimetics. Although we found that AmTRP-R is highly promiscuous, activated by various ligands including two VdNTL peptides when a total of 36 ligands were tested, we serendipitously found that peptides carrying the C-terminal motif -FWxxRamide are highly specific to VdTRP-R. This motif can serve as a seed sequence for designing a VdTRP-R-specific agonist. PMID- 26817787 TI - Behavioural effects of PNU-282987 and stress in an animal model of Alzheimer's disease. AB - BACKGROUND: Cholinergic deficits play an important role in both cognitive and behavioural alterations in Alzheimer's disease. This study was aimed at evaluating the possible therapeutic role of PNU-282987 (PNU), an alpha7 nicotinic cholinergic receptor agonist, and the possible effects of stress in precipitating the onset of behavioural deficits in animals with susceptibility to Alzheimer's disease. METHODS: B6C3-Tg mice with susceptibility to Alzheimer's disease and wild-type mice either with or without restraint stress received 0- or 1-mg/kg PNU. At 12 months old, mice were evaluated for activity levels, anxiety-like levels, and spatial learning and memory. RESULTS: Data did not show the effects of PNU on activity and anxiety-like behaviour. No effect of PNU on acquisition of a spatial learning task was detected, but a reversal of stress effects on retention in the Morris water maze was observed in transgenic mice. CONCLUSIONS: Further studies are needed in order to better understand the role of alpha7 nicotinic cholinergic receptor agonists in motor activity, anxiety, and spatial learning and memory and to develop more accurate pharmacological treatment of psychopathological diseases. PMID- 26817785 TI - Plasmodium knowlesi transmission: integrating quantitative approaches from epidemiology and ecology to understand malaria as a zoonosis. AB - The public health threat posed by zoonotic Plasmodium knowlesi appears to be growing: it is increasingly reported across South East Asia, and is the leading cause of malaria in Malaysian Borneo. Plasmodium knowlesi threatens progress towards malaria elimination as aspects of its transmission, such as spillover from wildlife reservoirs and reliance on outdoor-biting vectors, may limit the effectiveness of conventional methods of malaria control. The development of new quantitative approaches that address the ecological complexity of P. knowlesi, particularly through a focus on its primary reservoir hosts, will be required to control it. Here, we review what is known about P. knowlesi transmission, identify key knowledge gaps in the context of current approaches to transmission modelling, and discuss the integration of these approaches with clinical parasitology and geostatistical analysis. We highlight the need to incorporate the influences of fine-scale spatial variation, rapid changes to the landscape, and reservoir population and transmission dynamics. The proposed integrated approach would address the unique challenges posed by malaria as a zoonosis, aid the identification of transmission hotspots, provide insight into the mechanistic links between incidence and land use change and support the design of appropriate interventions. PMID- 26817788 TI - Evaluation of lignan (-)-cubebin extracted from Piper cubeba on human colon adenocarcinoma cells (HT29). AB - The dibenzylbutyrolactone lignan (-)-cubebin, which is extracted from the seeds of the pepper Piper cubeba, has shown promise as an anti-inflammatory, analgesic, leishmanicidal, antiproliferative, and trypanocidal compound. Given the therapeutic potential of (-)-cubebin, this study aimed to investigate its safety profile by analyzing cytotoxicity, mutagenicity, cell proliferation kinetics, induction of apoptosis, and expression of pro-apoptotic genes in human colon adenocarcinoma cells (HT29) exposed to (-)-cubebin. MTT cytotoxicity assays demonstrated that (-)-cubebin was cytotoxic only at 280 uM, whereas it was not cytotoxic at 2.8, 14, or 28 uM. Data demonstrated that (-)-cubebin was not mutagenic as evidenced by a micronucleus (MN) assay, did not alter cell-growth kinetics over 4 d, and showed absence of induced apoptosis after 24 h. Further, CASP8 and CASP9 gene expression was not markedly changed in HT29 cells exposed to 28 uM or 70 uM (-)-cubebin for 12 h. Based on our observations, (-)-cubebin was cytotoxic at a concentration of 280 uM, suggesting that the use of this concentration should be avoided. However, lower concentrations exerted no apparent damaging effects, indicating that this lignan is safe to use for pharmacological purposes at certain concentrations. PMID- 26817789 TI - A randomised controlled trial of cognitive aids for emergency airway equipment preparation in a Paediatric Emergency Department. AB - BACKGROUND: Safety of emergency intubation may be improved by standardising equipment preparation; the efficacy of cognitive aids is unknown. METHODS: This randomised controlled trial compared no cognitive aid (control) with the use of a checklist or picture template for emergency airway equipment preparation in the Emergency Department of The Royal Children's Hospital, Melbourne. RESULTS: Sixty three participants were recruited, 21 randomised to each group. Equal numbers of nursing, junior medical, and senior medical staff were included in each group. Compared to controls, the checklist or template group had significantly lower equipment omission rates (median 30% IQR 20-40% control, median 10% IQR 5-10 % checklist, median 10% IQR 5-20% template; p < 0.05). The combined omission rate and sizing error rate was lower using a checklist or template (median 35 % IQR 30 45 % control, median 15% IQR 10-20% checklist, median 15% IQR 10-30% template; p < 0.05). The template group had less variation in equipment location compared to checklist or controls. There was no significant difference in preparation time in controls (mean 3 min 14 s sd 56 s) compared to checklist (mean 3 min 46 s sd 1 min 15 s) or template (mean 3 min 6 s sd 49 s; p = 0.06). DISCUSSION: Template use reduces variation in airway equipment location during preparation foremergency intubation, with an equivalent reduction in equipment omission rate to the use of a checklist. The use of a template for equipment preparation and a checklist for team, patient, and monitoring preparation may provide the best combination of both cognitive aids. CONCLUSIONS: The use of a cognitive aid for emergency airway equipment preparation reduces errors of omission. Template utilisation reduces variation in equipment location. TRIAL REGISTRATION: Australian and New Zealand Trials Registry (ACTRN12615000541505). PMID- 26817790 TI - A Cross-Disorder Method to Identify Novel Candidate Genes for Developmental Brain Disorders. AB - IMPORTANCE: Developmental brain disorders are a group of clinically and genetically heterogeneous disorders characterized by high heritability. Specific highly penetrant genetic causes can often be shared by a subset of individuals with different phenotypic features, and recent advances in genome sequencing have allowed the rapid and cost-effective identification of many of these pathogenic variants. OBJECTIVES: To identify novel candidate genes for developmental brain disorders and provide additional evidence of previously implicated genes. DATA SOURCES: The PubMed database was searched for studies published from March 28, 2003, through May 7, 2015, with large cohorts of individuals with developmental brain disorders. DATA EXTRACTION AND SYNTHESIS: A tiered, multilevel data integration approach was used, which intersects (1) whole-genome data from structural and sequence pathogenic loss-of-function (pLOF) variants, (2) phenotype data from 6 apparently distinct disorders (intellectual disability, autism, attention-deficit/hyperactivity disorder, schizophrenia, bipolar disorder, and epilepsy), and (3) additional data from large-scale studies, smaller cohorts, and case reports focusing on specific candidate genes. All candidate genes were ranked into 4 tiers based on the strength of evidence as follows: tier 1, genes with 3 or more de novo pathogenic loss-of-function variants; tier 2, genes with 2 de novo pathogenic loss-of-function variants; tier 3, genes with 1 de novo pathogenic loss-of-function variant; and tier 4, genes with only inherited (or unknown inheritance) pathogenic loss-of-function variants. MAIN OUTCOMES AND MEASURES: Development of a comprehensive knowledge base of candidate genes related to developmental brain disorders. Genes were prioritized based on the inheritance pattern and total number of pathogenic loss of-function variants identified amongst unrelated individuals with any one of six developmental brain disorders. STUDY SELECTION: A combination of phenotype-based and genotype-based literature review yielded 384 studies that used whole-genome or exome sequencing, chromosomal microarray analysis, and/or targeted sequencing to evaluate 1960 individuals with developmental brain disorders. RESULTS: Our initial phenotype-based literature review yielded 1911 individuals with pLOF variants involving 1034 genes from 118 studies. Filtering our results to genes with 2 or more pLOF variants identified in at least 2 unrelated individuals resulted in 241 genes from 1110 individuals. Of the 241 genes involved in brain disorders, 7 were novel high-confidence genes and 10 were novel putative candidate genes. Fifty-nine genes were ranked in tier 1, 44 in tier 2, 68 in tier 3, and 70 in tier 4. By transcending clinical diagnostic boundaries, the evidence level for 18 additional genes that were ranked 1 tier higher because of this cross-disorder approach was increased. CONCLUSIONS AND RELEVANCE: This approach increased the yield of gene discovery over what would be obtained if each disorder, type of genomic variant, and study design were analyzed independently. These results provide further support for shared genomic causes among apparently different disorders and demonstrate the clinical and genetic heterogeneity of developmental brain disorders. PMID- 26817791 TI - Treatment with bone-seeking radionuclides for painful bone metastases in patients with lung cancer: a systematic review. AB - Treatment with bone-seeking radionuclides may provide palliation from pain originating from bone metastases. However, most studies have been conducted in patients with prostate cancer and patients with breast cancer. We aimed to perform a systematic review of the use of radionuclide treatment in lung cancer in accordance with the PRISMA guidelines. In the eligible trials, pain relief was reported in 75% of the patients included in the studies. The onset of pain relief was seen within 1-5 weeks after treatment, lasting up to 6 months. However, the methodology in the included trials was poor-only two randomised trials were eligible, and none of them compared radionuclide treatments with placebo or best standard of care. The remaining trials were case series with inherent problems of methodology reporting. Particularly challenging was the lack of reporting of baseline disease status and use of prior/concomitant analgaesics. Large randomised controlled trials are needed to clarify the efficacy of radionuclide treatment in lung cancer. PMID- 26817793 TI - Evidence of increasing public participation in advance care planning: a comparison of polls in Alberta between 2007 and 2013. AB - BACKGROUND: Advance care planning (ACP) encompasses both verbal and written communications expressing preferences for future health and personal care and helps prepare people for healthcare decision-making in times of medical crisis. Healthcare systems are increasingly promoting ACP as a way to inform medical decision-making, but it is not clear how public engagement in ACP activities is changing over time. METHODS: Raw data from 3 independently conducted public polls on ACP engagement, in the same Canadian province, were analysed to assess whether participation in ACP activities changed over 6 years. RESULTS: Statistically significant increases were observed between 2007 and 2013 in: recognising the definition of ACP (54.8% to 80.3%, OR 3.37 (95% CI 2.68 to 4.24)), discussions about healthcare preferences with family (48.4% to 59.8%, OR 1.41 (95% CI 1.17 to 1.69)) and with healthcare providers (9.1% to 17.4%, OR 1.98 (95% CI 1.51 to 2.59)), written ACP plans (21% to 34.6%, OR 1.77 (95% CI 1.45 to 2.17)) and legal documentation (23.4% to 42.7%, OR 2.13 (95% CI 1.75 to 2.59)). These remained significant after adjusting for age, education and self-rated health status. CONCLUSIONS: ACP engagement increased over time, although the overall frequency remains low in certain elements such as discussing ACP with healthcare providers. We discuss factors that may be responsible for the increase and provide suggestions for healthcare systems or other public bodies seeking to stimulate engagement in ACP. PMID- 26817794 TI - Supracolloidal helices from soft Janus particles by tuning the particle softness. AB - Because of the unique architectures and promising potential applications of biomimetic helical structures in biotechnology and nanotechnology, the design and fabrication of these structures by experimentally realizable anisotropic colloidal particles remain one of the most challenging tasks in materials science. Here we show how soft Janus particles self-assemble into supracolloidal helices with distinctive structural characteristics, including single helices, double helices, and Bernal spirals, by appropriately tuning the particle softness. We further examine the kinetic mechanisms governing the formation of different helical structures by using particle-based dynamics simulations. Our results provide a new way for experimentally fabricating structure-controllable supracolloidal helices solely from the self-assembly of soft Janus particles. PMID- 26817795 TI - Computational study on donor-acceptor optical markers for Alzheimer's disease: a game of charge transfer and electron delocalization. AB - According to the amyloid cascade hypothesis, amyloid-beta (Abeta) deposition is a central event in the Alzheimer's disease and thus, detection of Abeta deposits is crucial to monitor the progression of the pathology. Despite its low tissue penetration, fluorescence imaging may become an alternative technique for identifying these deposits because it is less toxic and less costly than positron emission tomography. Suitable dyes, however, should emit in the near infrared (NIR) region, cross the blood-brain barrier and target Abeta aggregates. In this work, we use TD-DFT, AIMD simulations and protein energy landscape exploration (PELE) to analyze the photophysical properties of a family of donor-acceptor markers and their binding to amyloid fibrils. These markers are formed by N,N dimethylaniline donor and propanedinitrile acceptor groups separated by a spacer consisting of one, two or three conjugated double bonds. The smallest compound has a low emission wavelength, can deactivate through a non-radiative process involving a conical intersection and binds weakly to Abeta fibrils. In contrast, the largest dye is a suitable compound as it shows an emission wavelength in the NIR region, does not seem to relax through conical intersection processes and binds to Abeta fibrils strongly entering hydrophobic voids. Analysis of electronic excitations shows that the transition has an important charge transfer character that increases with the length of the spacer, the pi bridge being an active participant in the transition. Therefore, adding double bonds to the dye skeleton has two beneficial effects: (i) it increases the emission wavelength as it enlarges the pi system and (ii) it increases the charge transfer character of the transition, which increases the red-shifting of the emission wavelength in polar solvents. PMID- 26817796 TI - [Anesthesia for lower extremity vascular bypass with peripheral nerve block]. AB - Vascular bypass is a surgical procedure widely used to treat peripheral vascular disease. The intraoperative anesthetic technique and the most appropriate postoperative analgesia for these high-risk patients remain controversial. We present the case of a patient undergoing femoropopliteal-distal bypass in our service, presenting with relevant comorbidities to the choice of anesthetic technique. This patient had several determining factors of difficult airway, especially thoracic kyphoscoliosis, which prevented him from being properly positioned for airway management, and chronic lung disease. This patient was also taken antiplatelet drugs, which is a contraindication for neuraxial block. So, we chose the anesthetic technique of peripheral nerve block, specifically the blockade of femoral and sciatic nerves. PMID- 26817797 TI - Long-Term Distributed Repetitive Transcranial Magnetic Stimulation for Tinnitus: A Feasibility Study. AB - OBJECTIVES: To assess feasibility and tolerability of long-term distributed therapeutic rTMS for refractory tinnitus, distributed over seven months. MATERIALS AND METHODS: Eight subjects with refractory tinnitus underwent five weekly sessions of 1800 pulses of 1 Hz rTMS targeted toward the temporoparietal junction. Five weeks later (study week 10), subjects meeting predefined responder criteria entered a monthly rTMS treatment phase, for the next five months. Outcome measures were subject satisfaction and compliance, tinnitus severity daily diaries, standardized tinnitus self-rating scales, and adverse events. RESULTS: Subject satisfaction was high, and compliance was virtually 100%. The tinnitus handicap inventory and mini-tinnitus questionnaire scores improved significantly at study week 5 compared with baseline. There were four responders at study week 5; three responders at study week 10; and one responder at study week 30. There were no serious adverse events. CONCLUSIONS: Our study demonstrated that rTMS can be delivered in a distributed schedule that is well tolerated, feasible and may prove to be clinically beneficial. A long-term distributed rTMS schedule for tinnitus may warrant investigation as an alternative to the short-term aggregated treatment schedules more frequently used previously. For the many varied therapeutic uses of rTMS (established and investigational), treatment schedules are relatively unexplored, and deserve further attention. PMID- 26817798 TI - Reducing Indoor Tanning--An Opportunity for Melanoma Prevention. PMID- 26817801 TI - Geometry-Related Right Ventricular Systolic Function Assessed by Longitudinal and Radial Right Ventricular Contractions. AB - The aim of our study was to evaluate the geometry-related right ventricular (RV) systolic function under normal hemodynamics by assessing the longitudinal and the radial RV contractions in children. We examined 953 healthy children. We measured tricuspid annular plane systolic excursion (TAPSE), RV anterior wall displacement from the interventricular septum (RVWD), and RV to left ventricular diameter ratio (RV/LV ratio) using M-mode echocardiography. The z-values were calculated as geometrical parameters of the TAPSE (z-TAPSE), the RVWD (z-RVWD), and the RV/LV ratio (z-RV/LV). The RV stroke volume (RVSV) was measured using Doppler echocardiography and standardized using the z-value (z-RVSV). The z-TAPSE was no or weakly negatively correlated with both the z-RVWD (r = -0.18, P < 0.0001) and the z-RV/LV (r = -0.12, P < 0.0001). In contrast, the z-RV/LV correlated positively with the z-RVWD (r = 0.61, P < 0.0001). The z-RVSV correlated only with the z-TAPSE (r = 0.30, P < 0.0001). Although the radial RV motion increases with the progression of RV dilatation, the RVSV is not associated with radial RV motion. In contrast, the RVSV relates to the longitudinal RV motion independently of the radial RV motion under the normal physiological condition. We presume that the RV contraction patterns change related to the RV geometry under various hemodynamic conditions. PMID- 26817802 TI - Z-Value of Mitral Annular Plane Systolic Excursion Is a Useful Indicator to Predict Left Ventricular Stroke Volume in Children: Comparing Longitudinal and Radial Contractions. PMID- 26817803 TI - Reply. PMID- 26817805 TI - [Therapeutic attitude of tutors and fourth year residents of Family and Community Medicine from Girona towards peri-articular infiltration]. PMID- 26817804 TI - Effects of norspermidine on Pseudomonas aeruginosa biofilm formation and eradication. AB - Biofilms are defined as aggregation of single cell microorganisms and associated with over 80% of all the microbial infections. Pseudomonas aeruginosa is a Gram negative opportunistic pathogen capable of leading to various infections in immunocompromised people. Recent studies showed that norspermidine, a kind of polyamine, prevented and disrupted biofilm formation by some Gram-negative bacterium. In this study, the effects of norspermidine on P. aeruginosa biofilm formation and eradication were tested. Microtiter plate combined with crystal violet staining was used to study the effects of norspermidine on P. aeruginosa initial attachment, then we employed SEM (scanning electron microscope), qRT-PCR, and QS-related virulence factor assays to investigate how norspermidine prevent biofilm formation by P. aeruginosa. We reported that high-dose norspermidine had bactericide effect on P. aeruginosa, and norspermidine began to inhibit biofilm formation and eradicate 24-h mature biofilm at concentration of 0.1 and 1 mmol/L, respectively, probably by preventing cell-surface attachment, inhibiting swimming motility, and downregulating QS-related genes expression. To investigate the potential utility of norspermidine in preventing device-related infections, we found that catheters immersed with norspermidine were effective in eradicating mature biofilm. These results suggest that norspermidine could be a potent antibiofilm agent for formulating strategies against P. aeruginosa biofilm. PMID- 26817806 TI - Redox imbalance in peripheral blood of type 1 myotonic dystrophy patients. AB - OBJECTIVES: The aim of our study was to determine if redox imbalance caused by the activities of antioxidant enzymes existed in erythrocytes of type 1 myotonic dystrophy (DM1) patients. METHODS: The activities of erythrocyte superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were measured in 30 DM1 patients and 15 healthy controls (HCs). The obtained values were correlated with the Muscular Impairment Rating Scale (MIRS) score and creatine kinase (CK). RESULTS: Superoxide dismutase and catalase activities were lower in DM1 patients compared to HCs. A positive correlation was found between disease duration and MIRS score as well as with glutathione reductase activity. In DM1 patients, there were positive correlations between catalase, glutathione peroxidase, and glutathione reductase activities. After sub-dividing DM1 patients according to CK levels, superoxide dismutase activity was still statistically different from HCs. However, catalase activity was significantly lower only in DM1 patients with increased CK. DISCUSSION: Undesirable alterations in antioxidant enzyme activities during DM1 disease progression may result in conditions favoring oxidative stress and changes in metabolism which together could contribute to muscle wasting. PMID- 26817808 TI - Different interventions for post-ischaemic stroke depression in different time periods: a single-blind randomized controlled trial with stratification by time after stroke. AB - OBJECTIVE: To determine the appropriate treatments for post-ischaemic stroke depression at different times after stroke. DESIGN: A single-blind, randomized, controlled trial that compared three intervention groups, with subgroups stratified by time after stroke. SETTING: Outpatient clinic. SUBJECTS: Eligible patients were recruited at discharge ( n = 73) and three ( n = 67), six ( n = 65), and nine months ( n = 69) after discharge, and patients completed mood questionnaires. INTERVENTIONS: Patients were randomly distributed into three groups: Group A received placebos and participated in general discussions; Group B, received citalopram and participated in general discussions; and Group C, received placebos and underwent cognitive behavioural therapy. All three groups participated in rehabilitation during three months of follow-up. MAIN MEASURES: Outcome was assessed three months after baseline using the 17-item Hamilton Depression Scale (HAMD17) and the Bech-Rafaelsen Melancholia Scale (MES). During treatment, the Udvalg for Kliniske Undersogelser side-effect scale was also administered. RESULTS: When stratification was not considered, the scores of Group B on the Melancholia Scale were lower than those of Group A ( P = 0.02); when the four time-based subgroups were analysed, significant differences were observed between Groups A and B (PMES = 0.02, PHAMD17 = 0.02) in the group recruited six months after discharge and between Groups A and C (PMES = 0.01) in the last time period nine months after discharge. CONCLUSIONS: The effects of citalopram or cognitive behavioural therapy is similar to the effect of rehabilitation alone for early-onset post-ischaemic depression; rehabilitation and citalopram for delayed-onset post-ischaemic depression; and rehabilitation and cognitive behavioural therapy for late-onset post-ischaemic depression are more effective than rehabilitation alone. PMID- 26817807 TI - Tracking official development assistance for reproductive health in conflict affected countries: 2002-2011. AB - OBJECTIVE: To provide information on trends on official development assistance (ODA) disbursement patterns for reproductive health activities in 18 conflict affected countries. DESIGN: Secondary data analysis. SAMPLE: 18 conflict-affected countries and 36 non-conflict-affected countries. METHODS: The Creditor Reporting System (CRS) database was analyzed for ODA disbursement for direct and indirect reproductive health activities to 18 conflict-affected countries (2002-2011). A comparative analysis was also made with 36 non-conflict-affected counties in the same 'least-developed' income category. Multivariate regression analyses examined associations between conflict status and reproductive health ODA and between reproductive needs and ODA disbursements. MAIN OUTCOME MEASURES: Patterns of ODA disbursements (constant U.S. dollars) for reproductive health activities. RESULTS: The average annual ODA disbursed for reproductive health to 18 conflict affected countries from 2002 to 2011 was US$ 1.93 per person per year. There was an increase of 298% in ODA for reproductive health activities to the conflict affected countries between 2002 and 2011; 56% of this increase was due to increases in HIV/AIDS funding. The average annual per capita reproductive health ODA disbursed to least-developed non-conflict-affected countries was 57% higher than to least-developed conflict-affected countries. Regression analyses confirmed disparities in ODA to and between conflict-affected countries. CONCLUSIONS: Despite increases in ODA for reproductive health for conflict affected countries (albeit largely for HIV/AIDS activities), considerable disparities remains. TWEETABLE ABSTRACT: Study tracking 10 years of aid for reproductive aid shows major disparities for conflict-affected countries. PMID- 26817809 TI - Effects of inspiratory muscle training on pulmonary function, respiratory muscle strength and functional capacity in patients with atrial fibrillation: a randomized controlled trial. AB - OBJECTIVE: To investigate the effects of inspiratory muscle training on pulmonary function, respiratory muscle strength and functional capacity in patients with atrial fibrillation. DESIGN: Prospective randomized controlled single-blind study. SETTING: Cardiology department of a university hospital. SUBJECTS: A total of 38 patients with permanent atrial fibrillation were randomly allocated to either a treatment group (n = 19; age 66.2 years (8.8)) or a control group (n = 19; age 67.1 years (6.4)). METHODS: The training group received inspiratory muscle training at 30% of maximal inspiratory pressure for 15 minutes twice a day, 7 days a week, for 12 weeks alongside the standard medical treatment. The control group received standard medical treatment only. Spirometry, maximal inspiratory and expiratory pressures and 6-minute walking distance was measured at the beginning and end of the study. RESULTS: There was a significant increase in maximal inspiratory pressure (27.94 cmH2O (8.90)), maximal expiratory pressure (24.53 cmH2O (10.34)), forced vital capacity (10.29% (8.18) predicted), forced expiratory volume in one second (13.88% (13.42) predicted), forced expiratory flow 25%-75% (14.82% (12.44) predicted), peak expiratory flow (19.82% (15.62) predicted) and 6-minute walking distance (55.53 m (14.13)) in the training group (p < 0.01). No significant changes occurred in the control group (p > 0.05). CONCLUSION: Inspiratory muscle training can improve pulmonary function, respiratory muscle strength and functional capacity in patients with atrial fibrillation. PMID- 26817810 TI - A population study of correlates of social participation in older adults with age related vision loss. AB - OBJECTIVE: To examine personal characteristics, disease-related impairment variables, activity limitations, and environmental factors as correlates of social participation in older adults with vision loss guided by the World Health Organization's International Classification of Functioning, Disability and Health Model. DESIGN: Baseline data of a larger longitudinal study. SETTING: Community based vision rehabilitation agency. SUBJECTS: A total of 364 older adults with significant vision impairment due to age-related macular degeneration. MAIN MEASURES: In-person interviews assessing social participation (i.e. frequency of social support contacts, social/leisure challenges faced due to vision loss, and of social support provided to others) and hypothesized correlates (e.g. visual acuity test, Functional Vision Screening Questionnaire, ratings of attachment to house and neighborhood, environmental modifications in home). RESULTS: Regression analyses showed that indicators of physical, social, and mental functioning (e.g. better visual function, fewer difficulties with instrumental activities of daily living, fewer depressive symptoms) were positively related to social participation indicators (greater social contacts, less challenges in social/leisure domains, and providing more support to others). Environmental factors also emerged as independent correlates of social participation indicators when functional variables were controlled. That is, participants reporting higher attachment to their neighborhood and better income adequacy reported having more social contacts; and those implementing more environmental strategies were more likely to report greater challenges in social and leisure domains. Better income adequacy and living with more people were related to providing more social support to others. CONCLUSION: Environmental variables may play a role in the social participation of older adults with age-related macular degeneration. PMID- 26817811 TI - Prevalence, stability, 1-year incidence and predictors of depressive symptoms among Norwegian adolescents in the general population as measured by the Short Mood and Feelings Questionnaire. AB - Background In numerous surveys the prevalence of depressive symptoms in adolescents has been examined in single sites and at one time point. Aims We examined depressive symptoms among adolescents aged 10-19 years in four different large school samples including two cohorts over a 10-year period in different locations in the same health region in central Norway including a total of 5804 adolescents. Two cohorts were retested within a 1-year time period to predict high versus low depressive symptom scores. Changes over a 6-year period in depressive symptom levels were examined in two of the samples of 12-14-year olds. Methods Depressive symptoms were estimated by the 13-item Short Mood and Feelings Questionnaire (SMFQ). Covariates were student age, sex, school size and location. Results "Miserable or unhappy", "Tired", "Restlessness" and "Poor concentration" were the most commonly reported depressive symptoms. Depressive symptom levels and proportions of high scoring students were consistently higher among girls, in particular in mid and late adolescence. Poisson regression analysis showed that all SMFQ items significantly predicted total scores for the whole sample, while sex (girls having a higher risk) emerged as a consistent 1-year predictor of high depressive symptom levels. Conclusions The SMFQ constitutes a short, practical and feasible measure. We recommend that this standardized measure should be used in the assessment of depressive symptoms among adolescents in school, primary care and clinical settings but also to evaluate treatment outcome. High scorers should be evaluated in subsequent clinical interviews for the presence of a depressive disorder. PMID- 26817812 TI - On the use of speciation techniques and ab initio modelling to understand tetravalent actinide behavior in a biological medium: An(IV)DTPA case. AB - In the case of an accidental nuclear event, contamination of human bodies by actinide elements may occur. Such elements have the particularity to exhibit both radiological and chemical toxicities that may induce severe damages at several levels, depending on the biokinetics of the element. In order to eliminate the actinide elements before they are stored in target organs (liver, kidneys, or bone, depending on the element), sequestering agents must be quickly injected. However, to date, there is still no ideal sequestering agent, despite the recent interest in this topic due to contamination concerns. DTPA (diethylene triamine pentaacetic acid) is currently generating interest for the development of oral or alternative self-administrable forms. Although biokinetics data are mostly available, molecular scale characterization of actinide-DTPA complexes is still scarce. Nevertheless, strong interest is growing in the characterization of An(IV)DTPA(-) complexes at the molecular level because this opens the way for predicting the stability constants of unknown systems or even for developing new analytical strategies aimed at better and more selective decorporation. For this purpose, Extended X-ray Absorption Fine Structure (EXAFS) and Ab Initio Molecular Dynamics (AIMD) investigations were undertaken and compared with capillary electrophoresis (CE) used in a very unusual way. Indeed, it is commonly believed that CE is incapable of extracting structural information. In capillary electrophoresis, the electrophoretic mobility of an ion is a function of its charge and size. Despite very similar ratios, partial separations between An(IV)DTPA(-) species (An(IV) = Th, U, Np, Pu) were obtained. A linear relationship between the electrophoretic mobility and the actinide--oxygen distance calculated by AIMD was evidenced. As an example, the interpolated U-O distances in U(IV)DTPA(-) from CE-ICPMS experiments, EXAFS, AIMD, and the relationship between the stability constants and the ratio z/dAn-O, are all in agreement. This results in the capability to evaluate the stability constants for the formation of Pa(IV)DTPA(-), Am(IV)DTPA(-) or Bk(IV)DTPA(-). PMID- 26817814 TI - A new insert sample approach to paper spray mass spectrometry: a paper substrate with paraffin barriers. AB - The analytical performance for paper spray (PS) using a new insert sample approach based on paper with paraffin barriers (PS-PB) is presented. The paraffin barrier is made using a simple, fast and cheap method based on the stamping of paraffin onto a paper surface. Typical operation conditions of paper spray such as the solvent volume applied on the paper surface, and the paper substrate type are evaluated. A paper substrate with paraffin barriers shows better performance on analysis of a range of typical analytes when compared to the conventional PS MS using normal paper (PS-NP) and PS-MS using paper with two rounded corners (PS RC). PS-PB was applied to detect sugars and their inhibitors in sugarcane bagasse liquors from a second generation ethanol process. Moreover, the PS-PB proved to be excellent, showing results for the quantification of glucose in hydrolysis liquors with excellent linearity (R(2) = 0.99), limits of detection (2.77 mmol L( 1)) and quantification (9.27 mmol L(-1)). The results are better than for PS-NP and PS-RC. The PS-PB was also excellent in performance when compared with the HPLC-UV method for glucose quantification on hydrolysis of liquor samples. PMID- 26817813 TI - Serological evidence of H9N2 avian influenza virus exposure among poultry workers from Fars province of Iran. AB - BACKGROUND: Since the 1990s, influenza A viruses of the H9N2 subtype have been causing infections in the poultry population around the globe. This influenza subtype is widely circulating in poultry and human cases of AI H9N2 have been sporadically reported in countries where this virus is endemic in domestic birds. The wide circulation of H9N2 viruses throughout Europe and Asia along with their ability to cause direct infection in mammals and humans, raises public health concerns. H9N2 AI was reported for the first time in Iran in 1998 and at present it is endemic in poultry. This study was carried out to evaluate the exposure to H9N2 AI viruses among poultry workers from the Fars province. METHODS: 100 poultry workers and 100 healthy individuals with no professional exposure to poultry took part in this study. Serum samples were tested for antibodies against two distinct H9N2 avian influenza viruses, which showed different phylogenetic clustering and important molecular differences, such as at the amino acid (aa) position 226 (Q/L) (H3 numbering), using haemagglutination inhibition (HI) and microneutralization (MN) assays. RESULTS: Results showed that 17 % of the poultry workers were positive for the A/chicken/Iran/10VIR/854-5/2008 virus in MN test and 12 % in HI test using the titer >=40 as positive cut-off value. Only 2 % of the poultry workers were positive for the A/chicken/Iran/12VIR/9630/1998 virus. Seroprevalence of non exposed individuals for both H9N2 strains was below 3 % by both tests. Statistical analyses models showed that exposure to poultry significantly increases the risk of infection with H9N2 virus. CONCLUSIONS: The results have demonstrated that exposure to avian H9N2 viruses had occurred among poultry workers in the Fars province of Iran. Continuous surveillance programmes should be implemented to monitor the presence of avian influenza infections in humans and to evaluate their potential threat to poultry workers and public health. PMID- 26817815 TI - The impact of climate on the abundance of Musca sorbens, the vector of trachoma. AB - BACKGROUND: To assess the extent to which climate may affect the abundance of Musca sorbens, a putative vector of trachoma. DATA SOURCES: Studies were identified by systematically searching online databases including CAB abstracts, Embase, Global Health, Medline, Web of Science and BIOS Online, references from key articles, and the websites of relevant international agencies. METHODS: A systematic literature review was conducted of field and laboratory studies that reported the impact of climate factors (e.g., temperature, humidity) on the synanthropic fly Musca sorbens. Data were systematically extracted and studies assessed for quality by two readers. Study results were reported narratively. RESULTS: A total of 16 studies met the inclusion criteria but only three evaluated associations between climatic/abiotic factors and M. sorbens. Limited evidence indicates that M. sorbens abundance has an optimal temperature and humidity range. Thirteen studies reported seasonal patterns but no consistent pattern was found between season and the abundance of M. sorbens. CONCLUSIONS: The evidence base regarding the effect of climatic factors on M. sorbens is limited, so it is difficult to construct a biological model driven by climate for this species. A multivariate statistical approach based on the climate of sites where M. sorbens is found may better capture its complex relationship with climatic factors as well as aid in mapping the global range of M. sorbens. PMID- 26817816 TI - Energy and structure of bonds in the interaction of organic anions with layered double hydroxide nanosheets: A molecular dynamics study. AB - The application of hybrid and hierarchical nanomaterials based on layered hydroxides and oxyhydroxides of metals is a swiftly progressing field in biomedicine. Layered double hydroxides (LDH) possess a large specific surface area, significant surface electric charge and biocompatibility. Their physical and structural properties enable them to adsorb various kinds of anionic species and to transport them into cells. However, possible side effects resulting from the interaction of LDH with anions of the intercellular and intracellular medium need to be considered, since such interaction can potentially disrupt ion transport, signaling processes, apoptosis, nutrition and proliferation of living cells. In the present paper molecular dynamics is used to determine the energies of interaction of organic anions (aspartic acid, glutamic acid and bicarbonate) with a fragment of layered double hydroxide Mg/Al-LDH. The average number of hydrogen bonds between the anions and the hydroxide surface and characteristic binding configurations are determined. Possible effects of LDH on the cell resulting from binding of protein fragments and replacement of native intracellular anions with delivered anions are considered. PMID- 26817818 TI - Ultradispersed Nanoarchitecture of LiV3O8 Nanoparticle/Reduced Graphene Oxide with High-Capacity and Long-Life Lithium-Ion Battery Cathodes. AB - Lack of high-performance cathode materials has become the major barriers to lithium-ion battery applications in advanced communication equipment and electric vehicles. In this paper, we report a versatile interfacial reaction strategy, which is based on the idea of space confinement, for the synthesis of ultradispersed LiV3O8 nanoparticles (~10 nm) on graphene (denoted as LVO NPs-GNs) with an unprecedented degree of control on the separation and manipulation of the nucleation, growth, anchoring, and crystallization of nanoparticles in a water-in oil emulsion system over free growth in solution. The prepared LVO NPs-GNs composites displayed high performance as an cathode material for lithium-ion battery, including high reversible lithium storage capacity (237 mA h g(-1) after 200 cycles), high Coulombic efficiency (about 98%), excellent cycling stability and high rate capability (as high as 176 mA h g(-1) at 0.9 A g(-1), 128 mA h g( 1) at 1.5 A g(-1), 91 mA h g(-1) at 3 A g(-1) and 59 mA h g(-1) at 6 A g(-1), respectively). Very significantly, the preparation method employed can be easily adapted and may opens the door to complex hybrid materials design and engineering with graphene for advanced energy storage. PMID- 26817817 TI - Astragalus injection attenuates bleomycin-induced pulmonary fibrosis via down regulating Jagged1/Notch1 in lungs. AB - OBJECTIVES: Inhibition of Notch signalling is a potential therapeutic strategy for pulmonary fibrosis. This study was designed to investigate the antifibrosis effects and possible mechanism of astragalus injection (AI) on bleomycin (BLM) induced pulmonary fibrosis in rats. METHODS: Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in male SD rats. All rats received daily intraperitoneally administration of dexamethasone (DEX, 3 mg/kg), astragalus injection (AI, 8 g/kg) or saline 1 day after bleomycin instillation daily for 28 days. Histological changes in the lung were evaluated by haematoxylin and eosin and Masson's trichrome staining. The expression of alpha smooth muscle protein (alpha-SMA) was assayed by immunohistochemical (IHC). The mRNA and protein level of Jagged1, Notch1 and transforming growth factor-beta1 (TGF-beta1) was analysed by qPCR and Western blot. KEY FINDINGS: BLM-induced severe alveolitis and pulmonary fibrosis; together with significant elevation of alpha-SMA, TGF-beta1, Jagged1 and Notch1. Astragalus injection (AI, 8 g/kg) administration notably attenuated the degree of alveolitis and lung fibrosis, and markedly reduced the elevated levels of alpha-SMA, TGF-beta1, Jagged1 and Notch1 in lungs. CONCLUSIONS: Astragalus injection (AI, 8 g/kg) may exert protective effects on bleomycin-induced pulmonary fibrosis via downregulating Jagged1/Notch1 in lung. PMID- 26817819 TI - c-Myc and viral cofactor Kaposin B co-operate to elicit angiogenesis through modulating miRNome traits of endothelial cells. AB - BACKGROUND: MicroRNAs (miRNAs) have emerged as master regulators of angiogenesis and other cancer-related events. Discovering new angiogenesis-regulating microRNAs (angiomiRs) will eventually help in developing new therapeutic strategies for tumor angiogenesis and cardiovascular diseases. Kaposi's sarcoma (KS), which is induced by the etiological infectious agent KS-associated herpesvirus (KSHV), is a peculiar neoplasm that expresses both blood and lymphatic endothelial markers and possesses extensive neovasculature. Using KSHV and its proteins as baits will be an efficient way to discover new angiomiRs in endothelial cells. Kaposin B is one of the latent viral genes and is expressed in all KSHV tumor cells. Since Kaposin B is a nuclear protein with no DNA-binding domain, it may regulate gene expression by incorporating itself into a transcription complex. RESULTS: We demonstrated that c-Myc and Kaposin B form a transcription complex and bind to the miR-221/-222 promoter, thereby affecting their expression and anti-angiogenic ability. By small RNA sequencing (smRNA Seq), we revealed that 72.1% (173/240) of Kaposin B up-regulated and 46.5% (113/243) of Kaposin B down-regulated known miRNAs were regulated by c-Myc. We also found that 77 novel miRNA were up-regulated and 28 novel miRNAs were down regulated in cells expressing both c-Myc and Kaposin B compared with cells expressing Kaposin B only. The result was confirmed by RNA-IP-seq data. CONCLUSIONS: Our study identifies known and novel c-Myc-regulated microRNAs and reveals that a c-Myc-oriented program is coordinated by Kaposin B in KSHV infected cells. PMID- 26817820 TI - RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency. AB - Zinc-finger nuclease, transcription activator-like effector nuclease and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR associated protein 9) are becoming major tools for genome editing. Importantly, knock-in in several non-rodent species has been finally achieved thanks to these customizable nucleases; yet the rates remain to be further improved. We hypothesize that inhibiting non-homologous end joining (NHEJ) or enhancing homology-directed repair (HDR) will improve the nuclease-mediated knock-in efficiency. Here we show that the in vitro application of an HDR enhancer, RS-1, increases the knock-in efficiency by two- to five-fold at different loci, whereas NHEJ inhibitor SCR7 has minimal effects. We then apply RS-1 for animal production and have achieved multifold improvement on the knock-in rates as well. Our work presents tools to nuclease-mediated knock-in animal production, and sheds light on improving gene-targeting efficiencies on pluripotent stem cells. PMID- 26817821 TI - Quantitative clinical pharmacology practice for optimal use of antibiotics during the neonatal period. AB - INTRODUCTION: For safe and effective neonatal antibiotic therapy, knowledge of the pharmacokinetic parameters of antibacterial agents in neonates is a prerequisite. Fast maturational changes during the neonatal period influence pharmacokinetic and pharmacodynamic parameters and their variability. Consequently, the need for applying quantitative clinical pharmacology and determining optimal drug dosing regimens in neonates has become increasingly recognized. AREAS COVERED: Modern quantitative approaches, such as pharmacometrics, are increasingly utilized to characterize, understand and predict the pharmacokinetics of a drug and its effect, and to quantify the variability in the neonatal population. Individual factors, called covariates in modeling, are integrated in such approaches to explain inter-individual pharmacokinetic variability. Pharmacometrics has been shown to be a relevant tool to evaluate, optimize and individualize drug dosing regimens. EXPERT OPINION: Challenges for optimal use of antibiotics in neonates can largely be overcome with quantitative clinical pharmacology practice. Clinicians should be aware that there is a next step to support the clinical decision-making based on clinical characteristics and therapeutic drug monitoring, through Bayesian-based modeling and simulation methods. Pharmacometric modeling and simulation approaches permit us to characterize population average, inter-subject and intra-subject variability of pharmacokinetic parameters such as clearance and volume of distribution, and to identify and quantify key factors that influence the pharmacokinetic behavior of antibiotics during the neonatal period. PMID- 26817822 TI - Epigenome overlap measure (EPOM) for comparing tissue/cell types based on chromatin states. AB - BACKGROUND: The dynamics of epigenomic marks in their relevant chromatin states regulate distinct gene expression patterns, biological functions and phenotypic variations in biological processes. The availability of high-throughput epigenomic data generated by next-generation sequencing technologies allows a data-driven approach to evaluate the similarities and differences of diverse tissue and cell types in terms of epigenomic features. While ChromImpute has allowed for the imputation of large-scale epigenomic information to yield more robust data to capture meaningful relationships between biological samples, widely used methods such as hierarchical clustering and correlation analysis cannot adequately utilize epigenomic data to accurately reveal the distinction and grouping of different tissue and cell types. METHODS: We utilize a three-step testing procedure-ANOVA, t test and overlap test to identify tissue/cell-type- associated enhancers and promoters and to calculate a newly defined Epigenomic Overlap Measure (EPOM). EPOM results in a clear correspondence map of biological samples from different tissue and cell types through comparison of epigenomic marks evaluated in their relevant chromatin states. RESULTS: Correspondence maps by EPOM show strong capability in distinguishing and grouping different tissue and cell types and reveal biologically meaningful similarities between Heart and Muscle, Blood & T-cell and HSC & B-cell, Brain and Neurosphere, etc. The gene ontology enrichment analysis both supports and explains the discoveries made by EPOM and suggests that the associated enhancers and promoters demonstrate distinguishable functions across tissue and cell types. Moreover, the tissue/cell type-associated enhancers and promoters show enrichment in the disease-related SNPs that are also associated with the corresponding tissue or cell types. This agreement suggests the potential of identifying causal genetic variants relevant to cell-type-specific diseases from our identified associated enhancers and promoters. CONCLUSIONS: The proposed EPOM measure demonstrates superior capability in grouping and finding a clear correspondence map of biological samples from different tissue and cell types. The identified associated enhancers and promoters provide a comprehensive catalog to study distinct biological processes and disease variants in different tissue and cell types. Our results also find that the associated promoters exhibit more cell-type-specific functions than the associated enhancers do, suggesting that the non-associated promoters have more housekeeping functions than the non-associated enhancers. PMID- 26817823 TI - Spontaneous liquid crystal and ferromagnetic ordering of colloidal magnetic nanoplates. AB - Ferrofluids are familiar as colloidal suspensions of ferromagnetic nanoparticles in aqueous or organic solvents. The dispersed particles are randomly oriented but their moments become aligned if a magnetic field is applied, producing a variety of exotic and useful magnetomechanical effects. A longstanding interest and challenge has been to make such suspensions macroscopically ferromagnetic, that is having uniform magnetic alignment in the absence of a field. Here we report a fluid suspension of magnetic nanoplates that spontaneously aligns into an equilibrium nematic liquid crystal phase that is also macroscopically ferromagnetic. Its zero-field magnetization produces distinctive magnetic self interaction effects, including liquid crystal textures of fluid block domains arranged in closed flux loops, and makes this phase highly sensitive, with it dramatically changing shape even in the Earth's magnetic field. PMID- 26817824 TI - Prenatal exposure to soy and selenium reduces prostate cancer risk factors in TRAMP mice more than exposure beginning at six weeks. AB - BACKGROUND: Diets high in soy and selenium (Se) decrease prostate cancer risk factors in healthy rats. The purpose of this study was to determine whether treatment with high levels of soy and/or supplemental Se would decrease prostate cancer risk factors in the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mouse, and whether timing of the introduction of these nutrients would affect risk reduction. METHODS: Male hemizygous [C57BL/6 * FVB]F1 TRAMP mice were exposed to stock diets high or devoid of soy, with or without a supplement of Se methylselenocysteine (MSC) starting at conception (10 mg Se/L in drinking water of pregnant/nursing dams; daily bolus of 4 mg Se/kg body weight to pups after weaning) or at 6 weeks of age in a 2 * 2 factorial design. Mice were killed at 12 weeks (n per dietary treatment = 20-30). RESULTS: Liver and serum Se concentrations were increased by MSC supplementation (P < 0.001), high-soy diet (P < 0.05), and initiation of dietary treatments at conception (P < 0.05). MSC supplementation had greater effects in mice fed the zero-soy basal diet, compared to the high-soy formulation (Pinteraction < 0.01). These same three interventions, individually and interactively, decreased body weight and epididymal fat pad weights, and steady state levels of mRNA for Cyp19a1 (aromatase) and Srd5a1 (5alpha-reductase). In contrast, MSC was the only treatment that decreased urogenital tract weights (P < 0.001), serum IGF-1 levels (P < 0.002), and Gleason scores (P < 0.05). CONCLUSIONS: Supplemental MSC reduces risk of prostate cancer in TRAMP mice. Basal diet composition (zero- vs. high soy) can modify MSC's chemopreventive effects. Initiation of dietary treatments from conception maximizes chemopreventive effects of MSC. Prenatal Se status may have long-lasting effects on development and progression of prostate cancer. PMID- 26817825 TI - Drug repositioning for non-small cell lung cancer by using machine learning algorithms and topological graph theory. AB - BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the leading causes of death globally, and research into NSCLC has been accumulating steadily over several years. Drug repositioning is the current trend in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development process of drugs, as well as reducing side effects. RESULTS: This work integrates two approaches--machine learning algorithms and topological parameter-based classification--to develop a novel pipeline of drug repositioning to analyze four lung cancer microarray datasets, enriched biological processes, potential therapeutic drugs and targeted genes for NSCLC treatments. A total of 7 (8) and 11 (12) promising drugs (targeted genes) were discovered for treating early- and late-stage NSCLC, respectively. The effectiveness of these drugs is supported by the literature, experimentally determined in-vitro IC50 and clinical trials. This work provides better drug prediction accuracy than competitive research according to IC50 measurements. CONCLUSIONS: With the novel pipeline of drug repositioning, the discovery of enriched pathways and potential drugs related to NSCLC can provide insight into the key regulators of tumorigenesis and the treatment of NSCLC. Based on the verified effectiveness of the targeted drugs predicted by this pipeline, we suggest that our drug-finding pipeline is effective for repositioning drugs. PMID- 26817827 TI - Assessment of health services for people who use drugs in Central Asia: findings of a quantitative survey in Kazakhstan and Kyrgyzstan. AB - BACKGROUND: In Central Asia, there is a need to update information about the situation of people who use (opioid) drugs (PWUD), especially regarding their access to and utilization of health care services. The aim of the study was to gather information about two different groups of drug users in Kazakhstan and Kyrgyzstan. METHODS: In 2013, two groups of PWUD were recruited in Kazakhstan and in Kyrgyzstan in order to gather quantitative data via interviewer-administered questionnaires. PWUD registered with the Narcological Register were allocated to group A while non-registered PWUD were allocated to group B. Interviews were conducted in the office of the Narcological Register as well as in low-threshold facilities. Participants reported about their drug use patterns, health status, and utilization of health services as well as barriers to utilization. RESULTS: The sample consisted of N = 600 PWUD (301 registered and 299 non-registered PWUD) from Kazakhstan and N = 900 PWUD (450 registered and 450 non-registered PWUD) from Kyrgyzstan. Both groups-registered (group A) and non-registered (group B) consisted of mainly male long-term intravenous opioid users. We found high rates of current (last 30 days) opioid use (group A up to 70%; group B up to 84%). Most PWUD were burdened with poor physical and mental health. The prevalence of infectious diseases added up to 19% (group A) or 13% (group B) regarding HIV, 56% (group A) or 30% (group B) regarding HCV, and 24% (group A) or 20% (group B) regarding tuberculosis. Registered and non-registered PWUD reported high rates (95 or 82%) of lifetime use of health services for PWUD. Drug-related services were utilized less often, especially among the non-registered PWUD (13%). The most important barriers preventing PWUD from accessing services were the belief not to need treatment, doubts about the effectiveness of treatment, mistrust of treatment regime/staff, and fear of being registered with the Narcological Register (mainly group B). CONCLUSIONS: Results show that access to the health care system for non-registered PWUD is realized mainly through low-threshold facilities. Opioid substitution treatment, which is an important pillar in the treatment of PWUD, is normally only available for those registered with the Narcological Register. Instead, access to opioid substitution treatment (especially in Kazakhstan) should be expanded and granted without prior registration, as this poses an important barrier for PWUD's utilization of drug treatment services. Further, there seems to be a need for the provision of specific and target group-related information about drug treatment services in order to reduce existing reservations among PWUD as to the necessity and effectiveness of modern drug treatment. PMID- 26817826 TI - Structure of an E. coli integral membrane sulfurtransferase and its structural transition upon SCN(-) binding defined by EPR-based hybrid method. AB - Electron paramagnetic resonance (EPR)-based hybrid experimental and computational approaches were applied to determine the structure of a full-length E. coli integral membrane sulfurtransferase, dimeric YgaP, and its structural and dynamic changes upon ligand binding. The solution NMR structures of the YgaP transmembrane domain (TMD) and cytosolic catalytic rhodanese domain were reported recently, but the tertiary fold of full-length YgaP was not yet available. Here, systematic site-specific EPR analysis defined a helix-loop-helix secondary structure of the YagP-TMD monomers using mobility, accessibility and membrane immersion measurements. The tertiary folds of dimeric YgaP-TMD and full-length YgaP in detergent micelles were determined through inter- and intra-monomer distance mapping and rigid-body computation. Further EPR analysis demonstrated the tight packing of the two YgaP second transmembrane helices upon binding of the catalytic product SCN(-), which provides insight into the thiocyanate exportation mechanism of YgaP in the E. coli membrane. PMID- 26817828 TI - Serum uric acid is associated with non-dipping circadian pattern in young patients (30-40 years old) with newly diagnosed essential hypertension. AB - BACKGROUND: We aimed at evaluating the relationship between the circadian blood pressure rhythm and UA level in young patients (30-40 years old) with newly diagnosed essential hypertension. METHODS: The study included 62 essential hypertensive patients and 29 healthy controls (20 men, 35 +/- 3 years) divided into two groups according to 24-hour ABPM results: 30 dippers and 32 nondippers. RESULTS: Nondippers showed significantly higher both serum UA levels compared to dippers and controls (6.1 +/- 0.7, 5.2 +/- 0.9 and 4.1 +/- 0.9 mg/dL, p < 0.001, respectively); and high sensitivity C-reactive protein (hsCRP) (4.1 +/- 2.2 mg/L, 3.3 +/- 1.9 mg/L, and 1.4 +/- 0.9 mg/L, p < 0.001, respectively). After adjusting for age, sex, body mass index, smoking, creatinine levels, hsCRP and comorbidity, multivariate logistic regression analysis revealed an independent association between serum UA levels and nondipper pattern (OR 2.44, 95%CIs 1.4-4.1, p = 0.002). CONCLUSION: Serum UA is independently associated with nondipper circadian pattern in young patients with newly diagnosed essential hypertension. PMID- 26817829 TI - Genomic variations and distinct evolutionary rate of rare alleles in Arabidopsis thaliana. AB - BACKGROUND: The variation rate in genomic regions associated with different alleles, impacts to distinct evolutionary patterns involving rare alleles. The rare alleles bias towards genome-wide association studies (GWASs), aim to detect different variants at genomic loci associated with single-nucleotide polymorphisms (SNPs) inclined to produce different haplotypes. Here, we sequenced Arabidopsis thaliana and compared its coding and non-coding genomic regions with its closest outgroup relative, Arabidopsis lyrta, which accounted for the ancestral misinference. The use of genome-wide SNPs interpret the genetic architecture of rare alleles in Arabidopsis thaliana, elucidating a significant departure from a neutral evolutionary model and the pattern of polymorphisms around a selected locus will exclusively influence natural selection. RESULTS: We found 23.4% of the rare alleles existing randomly in the genome. Notably, in our results significant differences (P < 0.01) were estimated in the relative rates between rare versus intermediate alleles, between fixed versus non-fixed mutations, and between type I versus type II rare-mutations by using the chi (2) test. However, the rare alleles generating negative values of Tajima's D suggest that they generated under selective sweeps. Relative to polymorphic sites including SNPs, 67.5% of the fixed mutations were attributed, indicating major contributors to speciation. Substantially, an evolution occurred in the rare allele that was 1.42-times faster than that in a major haplotype. CONCLUSION: Our results interpret that rare alleles fits a random occurrence model, indicating that rare alleles occur at any locus in a genome and in any accession in a species. Based on the higher relative rate of derived to ancient mutations and higher average D xy, we conclude that rare alleles evolve faster than the higher frequency alleles. The rapid evolution of rare alleles indicates that they must have been newly generated with fixed mutations, compared with the other alleles. Eventually, PCR and sequencing results, in the flanking regions of rare allele loci confirm that they are of short extension, indicating the absence of a genome wide pattern for a rare haplotype. The indel-associated model for rare alleles assumes that indel-associated mutations only occur in an indel heterozygote. PMID- 26817830 TI - Wakayama symposium: interface between innate and adaptive immunity in dry eye disease. AB - Although the mechanism of dry eye disease is not clearly understood, it is certain that inflammation and the immune response play a major role in determining the health of the ocular surface in dry eye patients. Accurate ocular surface characterization during the early stages of dry eye disease is critical for successful treatment, because there exists no single standard, objective test to diagnose the early phase of dry eye disease. The treatment target should be direct to prevent the perpetuation of chronic inflammation and immune responses. Numerous studies have categorized dry eye disease as an autoimmune-related inflammatory disease. However, relatively little is known about how innate immune mechanisms act following a local insult, why some patients are particularly vulnerable, and why local inflammation fails to resolve in these patients. Within this review, particular attention will be given to the very early events and corresponding defense mechanism in dry eye disease. The transition from innate to adaptive immunity will also be discussed. PMID- 26817833 TI - Pentoxifylline: Evidence strong enough for renoprotection? PMID- 26817832 TI - Evidence of a causal relationship between high serum adiponectin levels and increased cardiovascular mortality rate in patients with type 2 diabetes. AB - BACKGROUND: Despite its beneficial role on insulin resistance and atherosclerosis, adiponectin has been repeatedly reported as an independent positive predictor of cardiovascular mortality. METHODS: A Mendelian randomization approach was used, in order to evaluate whether such counterintuitive association recognizes a cause-effect relationship. To this purpose, single nucleotide polymorphism rs822354 in the ADIPOQ locus which has been previously associated with serum adiponectin at genome-wide level, was used as an instrument variable. Our investigation was carried out in the Gargano Heart Study-prospective design, comprising 356 patients with type 2 diabetes, in whom both total and high molecular weight (HMW) adiponectin were measured and cardiovascular mortality was recorded (mean follow-up = 5.4 +/- 2.5 years; 58 events/1922 person-year). RESULTS: The A allele of rs822354 was associated with both total and HMW adiponectin [beta (SE) = 0.10 (0.042), p = 0.014 and 0.17 (0.06), p = 0.003; respectively]. In a Poisson model comprising age, sex, smoking habits, BMI, HbA1c, total cholesterol, HDL-cholesterol, triglycerides, insulin therapy and hypertension, both rs822354 (IRR = 1.94, 95 % CI 1.23-3.07; p = 0.005), as well as the genetic equivalent of total adiponectin change (IRR = 1.07, 95 % CI 1.02-1.12; p = 0.003) were significantly associated with cardiovascular mortality. The observed genetic effect was significantly greater than that exerted by the genetic equivalent change of serum adiponectin (p for IRR heterogeneity = 0.012). In the above-mentioned adjusted model, very similar results were obtained when HMW, rather than total, adiponectin was used as the exposure variable of interest. CONCLUSIONS: Our data suggest that the paradoxical association between high serum adiponectin levels and increased cardiovascular mortality rate is based on a cause-effect relationship, thus pointing to an unexpected deleterious role of adiponectin action/metabolism on atherosclerotic processes. PMID- 26817834 TI - Bone marrow manifestations in multicentric Castleman disease. AB - This study aimed to document the morphological and immunophenotypic features, and describe the diagnostic features of bone marrow (BM) involvement in human herpes virus 8 Multicentric Castleman disease (HHV8-MCD). BM trephine biopsy (BMTB) specimens from 28 patients were revisited. Samples were evaluated for expression of CD3, CD20, CD138, CD68R, glycophorin C, CD42b, HHV8-latency-associated nuclear antigen (LANA1), Epstein-Barr virus-encoded small RNA and light chains. Presence of significant numbers of HHV8-LANA1(+) lymphoid/plasmacytic cells, noted in 10/28 cases, was indicative of BM involvement and was associated with low CD4 and CD8 counts in peripheral blood. The characteristic morphological appearance of MCD seen in lymph nodes is a rare finding in BMTB. 4/5 cases with lymphoid aggregates were involved by MCD, whereas 6/23 cases without lymphoid aggregates were involved by MCD (P = 0.023). 9/18 cases with hypercellular marrow were involved by MCD, whilst only 1/8 cases with normo/hypocellular marrow showed involvement by MCD (P = 0.070). While 9/21 cases with increased marrow reticulin were involved by MCD, none of the cases with no increase in reticulin were involved by MCD (P = 0.080). Reactive plasmacytosis is a frequent finding. We conclude that bone marrow is involved in a significant proportion of patients with MCD (36%), and involvement can be identified by HHV8-LANA1 immunohistochemistry. PMID- 26817836 TI - Women's experiences of making healthcare decisions about their breast cancer: A phenomenological study. AB - There are few studies about how healthcare decisions are made for women with breast cancer in China and this knowledge is vital, both to further develop person-centered health care and to ensure that women have a voice in their healthcare decisions. This phenomenological study explored the meaning of women's lived experiences of making healthcare decisions about their breast cancer in China. Semistructured, in-depth interviews were conducted with a purposive sample of eight women with breast cancer. Data were analyzed using Colaizzi's phenomenological analytic method. The results of this study identified four themes: authority and expertise, lack of knowledge, family support, and Chinese cultural and social influences. Women were deferential to medical authority and perceived expertise, but they wanted to be involved to a greater degree in healthcare decisions. It is important for health professionals to optimize women's participation in decision-making by removing barriers and advocating on their behalf. PMID- 26817835 TI - Comparison of body mass index (BMI) with the CUN-BAE body adiposity estimator in the prediction of hypertension and type 2 diabetes. AB - BACKGROUND: Obesity is a world-wide epidemic whose prevalence is underestimated by BMI measurements, but CUN-BAE (Clinica Universidad de Navarra - Body Adiposity Estimator) estimates the percentage of body fat (BF) while incorporating information on sex and age, thus giving a better match. Our aim is to compare the BMI and CUN-BAE in determining the population attributable fraction (AFp) for obesity as a cause of chronic diseases. METHODS: We calculated the Pearson correlation coefficient between BMI and CUN-BAE, the Kappa index and the internal validity of the BMI. The risks of arterial hypertension (AHT) and diabetes mellitus (DM) and the AFp for obesity were assessed using both the BMI and CUN BAE. RESULTS: 3888 white subjects were investigated. The overall correlation between BMI and CUN-BAE was R(2) = 0.48, which improved when sex and age were taken into account (R(2) > 0.90). The Kappa coefficient for diagnosis of obesity was low (28.7 %). The AFp was 50 % higher for DM and double for AHT when CUN-BAE was used. CONCLUSIONS: The overall correlation between BMI and CUN-BAE was not good. The AFp of obesity for AHT and DM may be underestimated if assessed using the BMI, as may the prevalence of obesity when estimated from the percentage of BF. PMID- 26817837 TI - Ribosome Elongation Stall Directs Gene-specific Translation in the Integrated Stress Response. AB - Upon exposure to environmental stress, phosphorylation of the alpha subunit of eIF2 (eIF2alpha-P) represses global protein synthesis, coincident with preferential translation of gene transcripts that mitigate stress damage or alternatively trigger apoptosis. Because there are multiple mammalian eIF2 kinases, each responding to different stress arrangements, this translational control scheme is referred to as the integrated stress response (ISR). Included among the preferentially translated mRNAs induced by eIF2alpha-P is that encoding the transcription factor CHOP (DDIT3/GADD153). Enhanced levels of CHOP promote cell death when ISR signaling is insufficient to restore cell homeostasis. Preferential translation of CHOP mRNA occurs by a mechanism involving ribosome bypass of an inhibitory upstream ORF (uORF) situated in the 5'-leader of the CHOP mRNA. In this study, we used biochemical and genetic approaches to define the inhibitory features of the CHOP uORF and the biological consequences of loss of the CHOP uORF on CHOP expression during stress. We discovered that specific sequences within the CHOP uORF serve to stall elongating ribosomes and prevent ribosome reinitiation at the downstream CHOP coding sequence. As a consequence, deletion of the CHOP uORF substantially increases the levels and modifies the pattern of induction of CHOP expression in the ISR. Enhanced CHOP expression leads to increased expression of key CHOP target genes, culminating in increased cell death in response to stress. PMID- 26817838 TI - Rab8b Regulates Transport of West Nile Virus Particles from Recycling Endosomes. AB - West Nile virus (WNV) particles assemble at and bud into the endoplasmic reticulum (ER) and are secreted from infected cells through the secretory pathway. However, the host factor related to these steps is not fully understood. Rab proteins, belonging to the Ras superfamily, play essential roles in regulating many aspects of vesicular trafficking. In this study, we sought to determine which Rab proteins are involved in intracellular trafficking of nascent WNV particles. RNAi analysis revealed that Rab8b plays a role in WNV particle release. We found that Rab8 and WNV antigen were colocalized in WNV-infected human neuroblastoma cells, and that WNV infection enhanced Rab8 expression in the cells. In addition, the amount of WNV particles in the supernatant of Rab8b deficient cells was significantly decreased compared with that of wild-type cells. We also demonstrated that WNV particles accumulated in the recycling endosomes in WNV-infected cells. In summary, these results suggest that Rab8b is involved in trafficking of WNV particles from recycling endosomes to the plasma membrane. PMID- 26817839 TI - Post-endocytotic Deubiquitination and Degradation of the Metabotropic gamma Aminobutyric Acid Receptor by the Ubiquitin-specific Protease 14. AB - Mechanisms controlling the metabotropic gamma-aminobutyric acid receptor (GABAB) cell surface stability are still poorly understood. In contrast with many other G protein-coupled receptors (GPCR), it is not subject to agonist-promoted internalization, but is constitutively internalized and rapidly down-regulated. In search of novel interacting proteins regulating receptor fate, we report that the ubiquitin-specific protease 14 (USP14) interacts with the GABAB(1b)subunit's second intracellular loop. Probing the receptor for ubiquitination using bioluminescence resonance energy transfer (BRET), we detected a constitutive and phorbol 12-myristate 13-acetate (PMA)-induced ubiquitination of the receptor at the cell surface. PMA also increased internalization and accelerated receptor degradation. Overexpression of USP14 decreased ubiquitination while treatment with a small molecule inhibitor of the deubiquitinase (IU1) increased receptor ubiquitination. Treatment with the internalization inhibitor Dynasore blunted both USP14 and IU1 effects on the receptor ubiquitination state, suggesting a post-endocytic site of action. Overexpression of USP14 also led to an accelerated degradation of GABABin a catalytically independent fashion. We thus propose a model whereby cell surface ubiquitination precedes endocytosis, after which USP14 acts as an ubiquitin-binding protein that targets the ubiquitinated receptor to lysosomal degradation and promotes its deubiquitination. PMID- 26817840 TI - Structural Basis for the Inhibition of Voltage-gated Sodium Channels by Conotoxin MUOS-GVIIJ. AB - Cone snail toxins are well known blockers of voltage-gated sodium channels, a property that is of broad interest in biology and therapeutically in treating neuropathic pain and neurological disorders. Although most conotoxin channel blockers function by direct binding to a channel and disrupting its normal ion movement, conotoxin MUOS-GVIIJ channel blocking is unique, using both favorable binding interactions with the channel and a direct tether via an intermolecular disulfide bond. Disulfide exchange is possible because conotoxin MUOS-GVIIJ contains anS-cysteinylated Cys-24 residue that is capable of exchanging with a free cysteine thiol on the channel surface. Here, we present the solution structure of an analog of MUOS-GVIIJ (GVIIJ[C24S]) and the results of structure activity studies with synthetic MUOS-GVIIJ variants. GVIIJ[C24S] adopts an inhibitor cystine knot structure, with two antiparallel beta-strands stabilized by three disulfide bridges. The loop region linking the beta-strands (loop 4) presents residue 24 in a configuration where it could bind to the proposed free cysteine of the channel (Cys-910, rat NaV1.2 numbering; at site 8). The structure activity study shows that three residues (Lys-12, Arg-14, and Tyr-16) located in loop 2 and spatially close to residue 24 were also important for functional activity. We propose that the interaction of MUOS-GVIIJ with the channel depends on not only disulfide tethering via Cys-24 to a free cysteine at site 8 on the channel but also the participation of key residues of MUOS-GVIIJ on a distinct surface of the peptide. PMID- 26817841 TI - Scorpion Potassium Channel-blocking Defensin Highlights a Functional Link with Neurotoxin. AB - The structural similarity between defensins and scorpion neurotoxins suggests that they might have evolved from a common ancestor. However, there is no direct experimental evidence demonstrating a functional link between scorpion neurotoxins and defensins. The scorpion defensin BmKDfsin4 from Mesobuthus martensiiKarsch contains 37 amino acid residues and a conserved cystine stabilized alpha/beta structural fold. The recombinant BmKDfsin4, a classical defensin, has been found to have inhibitory activity against Gram-positive bacteria such as Staphylococcus aureus, Bacillus subtilis, and Micrococcus luteusas well as methicillin-resistant Staphylococcus aureus Interestingly, electrophysiological experiments showed that BmKDfsin4,like scorpion potassium channel neurotoxins, could effectively inhibit Kv1.1, Kv1.2, and Kv1.3 channel currents, and its IC50value for the Kv1.3 channel was 510.2 nm Similar to the structure-function relationships of classical scorpion potassium channel-blocking toxins, basic residues (Lys-13 and Arg-19) of BmKDfsin4 play critical roles in peptide-Kv1.3 channel interactions. Furthermore, mutagenesis and electrophysiological experiments demonstrated that the channel extracellular pore region is the binding site of BmKDfsin4, indicating that BmKDfsin4 adopts the same mechanism for blocking potassium channel currents as classical scorpion toxins. Taken together, our work identifies scorpion BmKDfsin4 as the first invertebrate defensin to block potassium channels. These findings not only demonstrate that defensins from invertebrate animals are a novel type of potassium channel blockers but also provide evidence of a functional link between defensins and neurotoxins. PMID- 26817842 TI - Store-operated Ca2+ Entry-associated Regulatory factor (SARAF) Plays an Important Role in the Regulation of Arachidonate-regulated Ca2+ (ARC) Channels. AB - The store-operated Ca(2+)entry-associated regulatory factor (SARAF) has recently been identified as a STIM1 regulatory protein that facilitates slow Ca(2+) dependent inactivation of store-operated Ca(2+)entry (SOCE). Both the store operated channels and the store-independent arachidonate-regulated Ca(2+)(ARC) channels are regulated by STIM1. In the present study, we show that, in addition to its location in the endoplasmic reticulum, SARAF is constitutively expressed in the plasma membrane, where it can interact with plasma membrane (PM)-resident ARC forming subunits in the neuroblastoma cell line SH-SY5Y. Using siRNA-based and overexpression approaches we report that SARAF negatively regulates store independent Ca(2+)entry via the ARC channels. Arachidonic acid (AA) increases the association of PM-resident SARAF with Orai1. Finally, our results indicate that SARAF modulates the ability of AA to promote cell survival in neuroblastoma cells. In addition to revealing new insight into the biology of ARC channels in neuroblastoma cells, these findings provide evidence for an unprecedented location of SARAF in the plasma membrane. PMID- 26817843 TI - Characterization of a Unique Pathway for 4-Cresol Catabolism Initiated by Phosphorylation in Corynebacterium glutamicum. AB - 4-Cresol is not only a significant synthetic intermediate for production of many aromatic chemicals, but also a priority environmental pollutant because of its toxicity to higher organisms. In our previous studies, a gene cluster implicated to be involved in 4-cresol catabolism, creCDEFGHIR, was identified in Corynebacterium glutamicum and partially characterized in vivo. In this work, we report on the discovery of a novel 4-cresol biodegradation pathway that employs phosphorylated intermediates. This unique pathway initiates with the phosphorylation of the hydroxyl group of 4-cresol, which is catalyzed by a novel 4-methylbenzyl phosphate synthase, CreHI. Next, a unique class I P450 system, CreJEF, specifically recognizes phosphorylated intermediates and successively oxidizes the aromatic methyl group into carboxylic acid functionality via alcohol and aldehyde intermediates. Moreover, CreD (phosphohydrolase), CreC (alcohol dehydrogenase), and CreG (aldehyde dehydrogenase) were also found to be required for efficient oxidative transformations in this pathway. Steady-state kinetic parameters (Km and kcat) for each catabolic step were determined, and these results suggest that kinetic controls serve a key role in directing the metabolic flux to the most energy effective route. PMID- 26817845 TI - Editing of Cellular Self-RNAs by Adenosine Deaminase ADAR1 Suppresses Innate Immune Stress Responses. AB - Adenosine deaminases acting on double-stranded RNA (ADARs) catalyze the deamination of adenosine (A) to produce inosine (I) in double-stranded (ds) RNA structures, a process known as A-to-I RNA editing. dsRNA is an important trigger of innate immune responses, including interferon (IFN) production and action. We examined the role of A-to-I RNA editing by two ADARs, ADAR1 and ADAR2, in the sensing of self-RNA in the absence of pathogen infection, leading to activation of IFN-induced, RNA-mediated responses in mouse embryo fibroblasts. IFN treatment of Adar1(-/-) cells lacking both the p110 constitutive and p150 IFN-inducible ADAR1 proteins induced formation of stress granules, whereas neither wild-type (WT) nor Adar2(-/-) cells displayed a comparable stress granule response following IFN treatment. Phosphorylation of protein synthesis initiation factor eIF2alpha at serine 51 was increased in IFN-treated Adar1(-/-) cells but not in either WT or Adar2(-/-) cells following IFN treatment. Analysis by deep sequencing of mouse exonic loci containing A-to-I-editing sites revealed that the majority of editing in mouse embryo fibroblasts was carried out by ADAR1. IFN treatment increased editing in both WT and Adar2(-/-) cells but not in either Adar1(-/-) or Adar1(-/-) (p150) cells or Stat1(-/-) or Stat2(-/-) cells. Hyper edited sites found in predicted duplex structures showed strand bias of editing for some RNAs. These results implicate ADAR1 p150 as the major A-to-I editor in mouse embryo fibroblasts, acting as a feedback suppressor of innate immune responses otherwise triggered by self-RNAs possessing regions of double-stranded character. PMID- 26817846 TI - A "Love" Dart Allohormone Identified in the Mucous Glands of Hermaphroditic Land Snails. AB - Animals have evolved many ways to enhance their own reproductive success. One bizarre sexual ritual is the "love" dart shooting of helicid snails, which has courted many theories regarding its precise function. Acting as a hypodermic needle, the dart transfers an allohormone that increases paternity success. Its precise physiological mechanism of action within the recipient snail is to close off the entrance to the sperm digestion organ via a contraction of the copulatory canal, thereby delaying the digestion of most donated sperm. In this study, we used the common garden snailCornu aspersumto identify the allohormone that is responsible for this physiological change in the female system of this simultaneous hermaphrodite. The love dart allohormone (LDA) was isolated from extracts derived from mucous glands that coat the dart before it is stabbed through the partner's body wall. We isolated LDA from extracts using bioassay guided contractility measurement of the copulatory canal. LDA is encoded within a 235-amino acid precursor protein containing multiple cleavage sites that, when cleaved, releases multiple bioactive peptides. Synthetic LDA also stimulated copulatory canal contractility. Combined with our finding that the protein amino acid sequence resembles previously described molluscan buccalin precursors, this indicates that LDA is partially conserved in helicid snails and less in other molluscan species. In summary, our study provides the full identification of an allohormone that is hypodermically injected via a love dart. More importantly, our findings have important consequences for understanding reproductive biology and the evolution of alternative reproductive strategies. PMID- 26817844 TI - Self-assembled Micelle Interfering RNA for Effective and Safe Targeting of Dysregulated Genes in Pulmonary Fibrosis. AB - The siRNA silencing approach has long been used as a method to regulate the expression of specific target genes in vitro and in vivo. However, the effectiveness of delivery and the nonspecific immune-stimulatory function of siRNA are the limiting factors for therapeutic applications of siRNAs. To overcome these limitations, we developed self-assembled micelle inhibitory RNA (SAMiRNA) nanoparticles made of individually biconjugated siRNAs with a hydrophilic polymer and lipid on their ends and characterized their stability, immune-stimulatory function, and in vivo silencing efficacy. SAMiRNAs form very stable nanoparticles with no significant degradation in size distribution and polydispersity index over 1 year. Overnight incubation of SAMiRNAs (3 MUm) on murine peripheral blood mononuclear cells did not cause any significant elaboration of innate immune cytokines such as TNF-alpha, IL-12, or IL-6, whereas unmodified siRNAs or liposomes or liposome complexes significantly stimulated the expression of these cytokines. Last, the in vivo silencing efficacy of SAMiRNAs was evaluated by targeting amphiregulin and connective tissue growth factor in bleomycin or TGF-beta transgenic animal models of pulmonary fibrosis. Intratracheal or intravenous delivery two or three times of amphiregulin or connective tissue growth factor SAMiRNAs significantly reduced the bleomycin- or TGF-beta-stimulated collagen accumulation in the lung and substantially restored the lung function of TGF-beta transgenic mice. This study demonstrates that SAMiRNA nanoparticle is a less toxic, stable siRNA silencing platform for efficient in vivo targeting of genes implicated in the pathogenesis of pulmonary fibrosis. PMID- 26817848 TI - Body mass index in acute heart failure: association with clinical profile, therapeutic management and in-hospital outcome. AB - BACKGROUND: Increased body mass index (BMI) is a risk factor for heart failure, but evidence regarding BMI in acute heart failure (AHF) remains inconclusive. We sought to compare the clinical profile, treatment and in-hospital outcome across BMI categories in a large international AHF cohort. METHODS: The Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF) is a retrospective survey on 4953 patients admitted for AHF from nine countries in Europe, Latin America, and Australia. Patients with unavailable BMI data or BMI <18.5 kg/m(2) were excluded. Clinical data and in-hospital mortality were compared among the following BMI categories: 18.5-24.9 kg/m(2) (normal weight), 25-29.9 kg/m(2) (overweight) and >=30 kg/m(2) (obese). RESULTS: Overweight/obese patients represented 75.7% of patients and had worse New York Heart Association class (P < 0.001) and higher admission systolic blood pressure (P < 0.001). The prevalence of comorbidities increased in parallel with BMI and included arterial hypertension, diabetes mellitus, dyslipidaemia (all P < 0.001), chronic obstructive pulmonary disease (P = 0.041) and chronic kidney disease (P = 0.056). Use of guideline-recommended medications also increased in parallel with BMI (angiotensin converting enzyme inhibitors/angiotensin II receptor blockers, P < 0.001; beta-blockers P < 0.001; mineralocorticoid receptors antagonist, P = 0.002). In-hospital mortality had a U-shaped relationship with BMI, with overweight patients having significantly lower rate (log-rank P = 0.027); this relationship vanished after adjustment for confounders. CONCLUSIONS: Overweight/obese patients represented the vast majority of AHF cases, had a higher prevalence of non-cardiovascular comorbidities and were more likely to receive guideline-recommended medications. The U-shaped relationship between in hospital mortality and BMI may be explained by differences in clinical profile and treatment and not by an effect of body composition per se. PMID- 26817847 TI - Identification of pH-sensing Sites in the Light Harvesting Complex Stress-related 3 Protein Essential for Triggering Non-photochemical Quenching in Chlamydomonas reinhardtii. AB - Light harvesting complex stress-related 3 (LHCSR3) is the protein essential for photoprotective excess energy dissipation (non-photochemical quenching, NPQ) in the model green algaChlamydomonas reinhardtii Activation of NPQ requires low pH in the thylakoid lumen, which is induced in excess light conditions and sensed by lumen-exposed acidic residues. In this work we have used site-specific mutagenesisin vivoandin vitrofor identification of the residues in LHCSR3 that are responsible for sensing lumen pH. Lumen-exposed protonatable residues, aspartate and glutamate, were mutated to asparagine and glutamine, respectively. By expression in a mutant lacking all LHCSR isoforms, residues Asp(117), Glu(221), and Glu(224)were shown to be essential for LHCSR3-dependent NPQ induction inC. reinhardtii Analysis of recombinant proteins carrying the same mutations refoldedin vitrowith pigments showed that the capacity of responding to low pH by decreasing the fluorescence lifetime, present in the wild-type protein, was lost. Consistent with a role in pH sensing, the mutations led to a substantial reduction in binding the NPQ inhibitor dicyclohexylcarbodiimide. PMID- 26817849 TI - A descriptive investigation of the impact of student research projects arising from elective research courses. AB - BACKGROUND: Pharmacy academicians have noted the need to develop research skills in student pharmacists. At the Gatton College of Pharmacy, significant focus has been placed on the development of research skills through offering elective research courses. In order to evaluate the impact of participation in the research elective(s), we analyzed college records and surveyed faculty members with regard to the number of poster/podium presentations, published peer-reviewed manuscripts, and funded projects. RESULTS: Student enrollment in the research elective sequence has increased over time and has resulted in 81 poster presentations, 14 podium presentations, and 15 peer-reviewed publications. CONCLUSIONS: Implementation of a research elective sequence and fostering of a research culture amongst the faculty and students has resulted in increased student engagement in research and related scholarly activities. PMID- 26817850 TI - International medical students' expectations and worries at the beginning of their medical education: a qualitative focus group study. AB - BACKGROUND: The number of international students has increased substantially within the last decade. Due to cultural barriers, this specific group faces diverse challenges. In comparison to German colleagues, international medical students perform significantly lower in clinical examinations and exceed the average duration of study; they suffer from personal distress as well as insufficient support. Within the present study, their individual perspectives, expectations, hopes and fears were examined. METHODS: Four focus groups with first-year international medical students (N = 16) were conducted in October 2013. Each 60- to 90-min discussion was audiotaped, transcribed and analysed using qualitative methods. RESULTS: International medical students go abroad in search of good study-conditions. For the choice of place of study, affordability, social ties as well as an educational system following the achievement principle are decisive factors. While contact with German-students and other international students is seen as beneficial, international medical students are most concerned to encounter problems and social exclusion due to language deficits and intercultural differences. CONCLUSIONS: Facilitating the access to university places, the provision of financial aid and, moreover, social support, nurturing cultural integration, would greatly benefit international medical students. Hereby, the establishment of specific medical language courses as well as programs fostering intercultural-relations could prove to be valuable. PMID- 26817851 TI - Validation study of HSCL-10, HSCL-6, WHO-5 and 3-key questions in 14-16 year ethnic minority adolescents. AB - BACKGROUND: There is a lack of validated instruments for detection of depression in ethnic minority adolescent patients in primary care. This study aimed to compare a subgroup of the bilingual, ethnic minority adolescents with the rest of the population using Hscl-10, Hscl-6, WHO-5 and 3-Key Questions for detection of depression in primary care. METHOD: This is a cross-sectional, multicenter study conducted in General Practice in Norway and Denmark. A minor bilingual non aggregated heterogenic ethnic minority group from non-European countries was compared with a major ethnic group of Norwegian/Danish adolescents. Participants completed questionnaires which were either mailed to them or found on our website. The Composite International Diagnostic Interview was used as gold standard. Depression classified by the International Classification of Diseases - 10. The Internal and external validity of the four questionnaires were examined. Optimal cut-off point for major depressive disorder was calculated using the Youden Index. RESULTS: 294 (77%) were interviewed; mean age was 15 years. The ethnic group comprised 44 (64% girls and 36% boys). Chronbach's alpha was above 0. 70 and area under curve was 0.80 or above for all instruments in the ethnic minority group. Cut-off points for major depressive disorder had sensitivities of 81% (Hscl-10), 82% (Hscl-6), 91% (Who-5) and 81% (3-key questions) in the ethnic minority group. Corresponding specificities were 80% (Hscl-10), 77% (Hscl-6), 80% (Who-5) and 67% (3-key questions). Cut-off points were the same Hscl-10, Who-5, the 3-key questions but differed for Hscl-6. CONCLUSION: Hscl-10, Hscl-6, WHO-5 and 3-key questions seem to be valid instruments for detection of depression in bilingual, ethnic minority adolescents in primary care. PMID- 26817853 TI - Decline in ethical concerns about reproductive technologies among a representative sample of US women. AB - Public awareness and utilization of assisted reproductive technology has been increasing, but little is known about changes in ethical concerns over time. The National Survey of Fertility Barriers, a national, probability-based sample of US women, asked 2031 women the same set of questions about ethical concerns regarding six reproductive technologies on two separate occasions approximately 3 years apart. At Wave 1 (2004-2007), women had more concerns about treatments entailing the involvement of a third party than about treatments that did not. Ethical concerns declined between Wave 1 and Wave 2, but they declined faster for treatments entailing the involvement of a third party. Ethical concerns declined faster for women with greater levels of concern at Wave 1. Initial ethical concerns were higher, and there was less of a decline in ethical concerns for women with higher initial levels of religiosity. PMID- 26817852 TI - Mental Health First Aid in Rural Communities: Appropriateness and Outcomes. AB - PURPOSE: Mental Health First Aid (MHFA), an early intervention training program for general audiences, has been promoted as a means for improving population level behavioral health (BH) in rural communities by encouraging treatment seeking. This study examined MHFA's appropriateness and impacts in rural contexts. METHODS: We used a mixed-methods approach to study MHFA trainings conducted from November 2012 through September 2013 in rural communities across the country. DATA SOURCES: (a) posttraining questionnaires completed by 44,273 MHFA participants at 2,651 rural and urban trainings in 50 US states; (b) administrative data on these trainings; and (c) interviews with 16 key informants who had taught, sponsored, or participated in rural MHFA. Measure of Rurality: Rural-Urban Commuting Area Codes. ANALYSES: Chi-square tests were conducted on questionnaire data. Structural, descriptive, and pattern coding techniques were used to analyze interview data. FINDINGS: MHFA appears aligned with some key rural needs. MHFA may help to reduce unmet need for BH treatment in rural communities by raising awareness of BH issues and mitigating stigma, thereby promoting appropriate treatment-seeking. However, rural infrastructure deficits may limit some communities' ability to meet new demand generated by MHFA. MHFA may help motivate rural communities to develop initiatives for strengthening infrastructure, but additional tools and consultation may be needed. CONCLUSIONS: This study provides preliminary evidence that MHFA holds promise for improving rural BH. MHFA alone cannot compensate for weaknesses in rural BH infrastructure. PMID- 26817855 TI - The new Clinical and Experimental Allergy editorial team. PMID- 26817856 TI - Non-specific airway hyperreactivity in asthma: a clinical correlate to ... what exactly? PMID- 26817858 TI - Molecular-based allergy diagnosis of allergic bronchopulmonary aspergillosis in Aspergillus fumigatus-sensitized Japanese patients. PMID- 26817857 TI - From the hygiene hypothesis to A20: the protective effect of endotoxins against asthma development. PMID- 26817860 TI - Non-linear associations of risk factors with mild hypoglycemia among Chinese patients with type 2 diabetes. AB - AIMS: The present study aimed to examine the nonlinear associations between risk factors and mild hypoglycemia in Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: From May 2013 to August 2013, we conducted a cross sectional survey of 6633 inpatients with T2DM and without severe hypoglycemia, aged 21-77 years, from 81 top tertiary hospitals in China. Mild hypoglycemia was defined as having hypoglycemia with symptoms in one month. Binary logistic regression analysis with restricted cubic splines was used to estimate odds ratio curves of non-linear risk factors for mild hypoglycemia. RESULTS: Increasing body mass index was associated with decreasing risk of mild hypoglycemia in a linear manner while age, duration of diabetes, glycated hemoglobin (HbA1c), mean artery pressure and lipids were associated with mild hypoglycemia in non-linear manners. Age >=40 years, duration >=2 years, HbA1c >=7.0-<11.5% (>=53-<102 mmol/mol), triglyceride >=1.7-<3.6 mmol/L, low-density lipoprotein cholesterol (LDL-C) >=2.6 <4.8 mmol/L, and high-density lipoprotein cholesterol (HDL-C) >=1.2-<4.8 mmol/L were associated with increased risks of mild hypoglycemia. CONCLUSIONS: Chinese T2DM patients with age>=40 years, duration of diabetes >=2-<6 years, HbA1c >=7.0 <11.5% (>=53-<102 mmol/mol), LDL-C >=2.6-<4.8mmol/L, HDL-C >=1.2-<4.8 mmol/L or triglyceride >=1.7-<3.6 mmol/L were at particularly high risk for mild hypoglycemia. PMID- 26817861 TI - Differentially Expressed miRNAs in Hepatocellular Carcinoma Target Genes in the Genetic Information Processing and Metabolism Pathways. AB - To date, studies of the roles of microRNAs (miRNAs) in hepatocellular carcinoma (HCC) have either focused on specific individual miRNAs and a small number of suspected targets or simply reported a list of differentially expressed miRNAs based on expression profiling. Here, we seek a more in-depth understanding of the roles of miRNAs and their targets in HCC by integrating the miRNA and messenger RNA (mRNA) expression profiles of tumorous and adjacent non-tumorous liver tissues of 100 HCC patients. We assessed the levels of 829 mature miRNAs, of which 32 were significantly differentially expressed. Statistical analysis indicates that six of these miRNAs regulate a significant proportion of their in silico predicted target mRNAs. Three of these miRNAs (miR-26a, miR-122, and miR 130a) were down-regulated in HCC, and their up-regulated gene targets are primarily associated with aberrant cell proliferation that involves DNA replication, transcription and nucleotide metabolism. The other three miRNAs (miR 21, miR-93, and miR-221) were up-regulated in HCC, and their down-regulated gene targets are primarily involved in metabolism and immune system processes. We further found evidence for a coordinated miRNA-induced regulation of important cellular processes, a finding to be considered when designing therapeutic applications based on miRNAs. PMID- 26817862 TI - Identify Melatonin as a Novel Therapeutic Reagent in the Treatment of 1 Bromopropane(1-BP) Intoxication. AB - 1-Bromopropane (1-BP) has been used as an alternative for fluoride compounds and 1-BP intoxication may involve lung, liver, and central neural system (CNS). Our previous studies showed that 1-BP impaired memory ability by compromising antioxidant cellular defenses. Melatonin is a powerful endogenousantioxidant, and the objective of this study was to explore the therapeutic role of melatonin in the treatment of 1-BP intoxication. Rats were intragastrically treated with 1-BP with or without melatonin, and then sacrificed on 27th day after 1-BP administration. The Morris water maze (MWM) test was used to evaluate the spatial learning and memory ability of the experimental animals, and NeuN staining was performed to assess neuron loss in hippocampus. We found that rats treated with 1 BP spent more time and swam longer distance before landing on the hidden platform with a comparable swimming speed, which was markedly mitigated by the pretreatment with melatonin in a concentration-dependent manner. In addition, 1 BP-induced notable decrease in neuron population in hippocampus by promoting apoptosis, and melatonin pretreatment attenuated those changes in brain. The GSH/GSSG ratio was proportionately decreased and heme oxygenase 1 was increased in the rats exposed to 1-BP (Figure 6), and administration of melatonin restored them. Meanwhile, MDA, the level of lipid peroxidation product, was significantly increased upon exposed to 1-BP, which was significantly attenuated by melatonin pretreatment, indicating that administration of 1-BP could interfere with redox homeostasis of brain in rat, and such 1-BP-induced biomedical changes were reversed by treatment with melatonin.We conclude that treatment with melatonin attenuates 1-BP-induced CNS toxicity through its ROS scavenging effect. PMID- 26817863 TI - Pathological Assessment of the AJCC Tumor Regression Grading System After Preoperative Chemoradiotherapy for Chinese Locally Advanced Rectal Cancer. AB - We used American Joint Committee on Cancer (AJCC) Staging Manual system to assess the prognostic significance of tumor regression grading (TRG) for locally advanced rectal cancer (LARC) (T3/4 or N+) patients who were treated with preoperative chemoradiotherapy (CRT).The 4 AJCC-TRG classifications were evaluated on surgical specimens from 295 LARC patients receiving CRT. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated using Kaplan Meier method and Cox regression model.Classifications of TRG 0, 1, 2, and 3 were found in 27.5%, 19.3%, 45.7%, and 7.5% of the resected specimens, respectively. Three-year OS was 95.5% for TRG0, 91.5% for TRG1, 84.8% for TRG2, and 85.7% for TRG3 (P = 0.035). Three-year DFS was 89.0% for TRG0, 74.4% for TRG1, 70.9% for TRG2, and 62% for TRG3 (P = 0.018). By multivariate analysis, AJCC-TRG (P = 0.033), residual lymph node metastasis (ypN+) (P < 0.001) and pretreatment CA19-9 level (P = 0.035) were significant predictors of OS. Pathological T category (P = 0.006) and nodal status (P < 0.001) after CRT were the most important independent prognostic factors for DFS.AJCC-TRG is a prognostic factor for LARC patients receiving CRT, independent of pathological staging. PMID- 26817864 TI - Influence of Educational Level, Stage, and Histological Type on Survival of Oral Cancer in a Brazilian Population: A Retrospective Study of 10 Years Observation. AB - The mortality rate associated with oral cancer is estimated at approximately 12,300 deaths per year, and the survival rate is only 40% to 50% for diagnosed patients and is closely related to the duration of time between disease perception and its diagnosis and treatment. Socioeconomic risk factors are determinants of the incidence and mortality related to oral cancer. We conducted a retrospective, cross-sectional study of 573 records of patients with oral cancer at Haroldo Juacaba Hospital - Cancer Institute of Ceara from 2000 to 2009 to evaluate the influence of socioeconomic factors on survival and epidemiological behavior of this neoplasia in a Brazilian population. In this study, patients with oral cancer were males greater than 60 years of age, presented squamous cell carcinoma in the floor of mouth and were characterized by low education levels. A total of 573 lesions were found in oral cavities. Cox proportional hazards regression model showed that the histological type, tumor stage, and low degree of education significantly influenced survival. A lower patient survival rate was correlated with a more advanced stage of disease and a worse prognosis. Squamous cell carcinoma is associated with a higher mortality when compared with other histological types of malign neoplasia. PMID- 26817865 TI - Radial EUS Examination Can be Helpful in Predicting the Severity of Acute Biliary Pancreatitis. AB - We investigated the utility of noncontrast enhanced endosonography (EUS) in predicting the severity of acute pancreatitis (AP) during the first 72 to 96 h of admission.In total, 187 patients with acute biliary pancreatitis were included. The patients were classified into 2 groups as having severe and mild AP according to the Modified Glasgow scoring and computerized tomography severity index (SI). The 158 cases with mild and 29 cases with severe AP had a similar age and sex distribution.Although none of the cases with mild AP developed morbidity and death, of the cases with severe AP, 16 developed serious morbidities and 5 died. On EUS examination, we looked for parenchymal findings, peripancreatic inflammatory signs, free or loculated fluid collections, and abnormalities of the common bile duct and the pancreatic channel. Statistical analysis indicated a significant relationship between the severity of AP with diffuse parenchymal edema, periparenchymal plastering, and/or diffuse retroperitoneal free fluid accumulation, and peri-pancreatic edema. We also defined an EUSSI and found that the EUSSI had sensitivity of 89.7%, specificity of 84.2%, positive predictivity value (PPV) of 88.9%, negative predictivity value (NPV) of 91.2%, and an accuracy of 87.9% in the differentiation of mild and severe AP. We found that the EUSSI had an accuracy of 72.4%, sensitivity of 75.4%, specificity of 65.1%, PPV of 69.3%, and NPV of 73.1% for determining mortality.Our data suggest that EUS allowed us to accurately predict the severity and mortality in nearly 90% of cases with AP. PMID- 26817866 TI - Characterization of Mycobacterium Abscessus Subtypes in Shanghai of China: Drug Sensitivity and Bacterial Epidemicity as well as Clinical Manifestations. AB - The aim of the study was to investigate the epidemic characteristics of Mycobacterium abscessus in Shanghai.Fifty-five strains from 55 M. abscessus pulmonary disease patients were isolated. Drug sensitivity was measured by a broth microdilution method. Subtypes of M. abscessus were identified by DNA sequencing. Multilocus sequence typing (MLST), mining spanning tree (MST), and pulsed-field gel electrophoresis (PFGE) were used to analyze sequence types (ST) and clonal complexes (CC). Clinical manifestations were assessed by CT imaging.We identified 42 A isolates, 11 M, and 2 B-subtypes. A and M were highly sensitive to tigecycline and amikacin (97.6-100%). The A-type easily developed drug resistance against clarithromycin. Both types were highly resistance to sulfonamides, moxifloxacin, doxycycline, imipenem, and tobramycin. MLST analysis identified 41 STs including 32 new STs. The MST algorithm distributed 55 isolates into 12 separate CC. The PFGE analysis exhibited 53 distinct restriction patterns and the M-type was closely clustered according to their ST and CC numbers. CT imaging showed that tree-in-bud and patch shadow were commonly observed in M type, whereas pulmonary cavities were often found in A-type infection patients (P < 0.001).ST1 in A and ST23 in M-type were the main epidemic strains in Shanghai. The M-type appeared to be prone to epidemic nosocomial transmission. PMID- 26817867 TI - Using a Harmonic Scalpel "Drilling and Clamping" Method to Implement Zero Ischemic Robotic-assisted Partial Nephrectomy: An Observation Case Report Study. AB - Robot-assisted partial nephrectomy (RAPN) has gradually become a popular minimally invasive nephron-sparing surgical option for small renal tumors. Ischemic injury should be minimized because it impacts renal function outcomes following partial nephrectomy. Herein, the authors detail the technique and present initial perioperative outcomes of our novel harmonic scalpel "drilling and clamping" method to implement zero-ischemic RAPN. The authors prospectively collected baseline and perioperative data of patients who underwent zero ischemic RAPN performed by our harmonic scalpel "drilling and clamping" method. From April 2012 to December 2014, a total of 19 consecutive zero ischemic RAPN procedures were performed by a single surgeon. For 18 of the 19 patients, RAPN using our harmonic scalpel "Drilling and Clamping" method was successfully completed without the need for hilar clamping. The median tumor size was 3.4 cm (range: 1.8 6.2); operative time was 3.2 hours (range: 1.9-4.5); blood loss was 100 mL (range: 30-950); and postoperative hospital stay was 4 days (3-26). One patient required intraoperative blood transfusion. Two patients had intra or postoperative complications: 1 was converted to traditional laparotomy because of massive bleeding, whereas another had postoperative stress ulcer. Pathology confirmed renal cell carcinoma in 13 patients (63.2%), angiomyolipoma in 6 patients: (31.5%), and oncocytoma in 1 patient (5.3%). Mean pre- and postoperative serum creatinine (0.82 mg/dL and 0.85 mg/dL, respectively), estimated glomerular filtration rate (84.12 and 82.18, respectively), and hemoglobin (13.27 g/dL and 12.71 g/dL, respectively) were comparable. The authors present a novel zero-ischemic technique for RAPN. They believe that this technique is feasible and reproducible. PMID- 26817868 TI - First Case Report of Smith-Magenis Syndrome (SMS) Among the Arab Community in Nazareth: View and Overview. AB - Smith-Magenis syndrome (SMS0) is a complex and rare genetic multisystem disorder characterized by a variable pattern of cognitive deficits accompanied by a1 distinctive behavioral phenotype. SMS is characterized by subtle facial dysmorphology, short stature, sleep disturbances, and neurobehavioral abnormalities. Little is known about the manifestation of his unique case among Arab population and its strategic treatment.This study comes to present a case of SMS in an Arab newborn male who was born in spontaneous delivery on June 29, 2015, with tachypnea, tracheomalacia, and mild hypotonia. The newborn was admitted on the Neonatal Intensive Care Unit (NICU), and various laboratory examinations and clinical examinations were performed.Throughout his hospitalization, feeding difficulties appeared and thus a peripheral venous catheter was inserted in the left leg.After 22 days of follow-up and hospitalizations, the patient status improved and he was discharged with recommendations to be in follow up in pediatric outpatient clinic.However, notwithstanding the different investigations, intermittent tachypnea continued at a rate of 72 to 77 breaths/min. Search for diagnosis begin intensively owing to persistence of tachypnia, mild hypotonia, feeding difficulties, sleep disturbances, and mild dysmorphic facial features. Suspicions of genetic abnormalities were considered and blood samples were sent for chromosome analysis and for fluorescent in situ hybridization (FISH) testing.The genetic results revealed the following: cytogenetic findings: 46, XY, del(17)(p11.2) and the FISH results: del(17)(p11.2p11.2) (D17S29). The chromosome diagnosis revealed an interstitial deletion of 17p11.2 and the diagnosis of the SMS was confirmed.Accurate clinical diagnosis, therapeutic assessments and a holistic management plans, including multidiscipline therapeutic strategies, periodic neuro-developmental assessments, and an early intervention programs, are recommended.However, cytogenetic analysis or FISH using an RAI1-specific probe is the most frequently used technique for DS. Sleep and behavioral disturbances treatment include a combination of the daytime dose of acebutolol with an evening oral dose of melatonin. Melatonin as chronobiotic, antioxidant, and analgesic agent showed to be effective in different primary sleep disorders and in those associated with neurobehavioral disorders. Based on the beneficial effect of melatonin, it will be useful to use serum levels of melatonin as a follow-up test. PMID- 26817869 TI - Is There an Association Between Magnetic Resonance Imaging and Neurological Signs in Patients With Vertebral Osteomyelitis?: A Retrospective Observational Study on 121 Patients. AB - Neurological complications can occur in up to 51% of vertebral osteomyelitis (VO) in surgical series. The aim of our study was to estimate the frequency of neurological signs in a nonselected population of patients with VO and to assess clinical and MRI changes associated with these complications.We reviewed medical charts of patients with VO from 2007 to 2014 in our University Hospital and their MRIs were analyzed by a radiologist blinded from clinical data. Neurological status was defined as follow: normal, minor signs (radiculalgia or sensory loss), and major signs (motor deficit and/or sphincter dysfunction).A total of 121 patients were included. Mean age was 64.3 years. Overall, 50 patients (40%) had neurological signs, 26 were major signs (21.5%). Neurological signs were present at the time of admission in 37 patients and happened secondarily in 13 cases. MRI changes associated with major neurological signs were: Cervical involvement (P = 0.011), dural sac compression (P = 0.0012), ventral effacement of the subarachnoidal space (P < 0.001), compressive myelopathy (P = 0.006). More than 50% of the vertebral body destruction (P = 0.017), angular kyphosis (P = 0.016) partial or complete destruction of posterior arch (P = 0.032) were also associated with these signs. Neither epidural abscesses, multifocal lesions, loss of disk height, nor nerve roots compression were associated with major neurological signs.Neurological signs occurred in 40% of our patients with one half being major signs. Cervical involvement, vertebral destruction, angular kyphosis, dural compression, effacement of subarachnoid space and compressive myelopathy on MRI were risk factors associated with neurological complications. PMID- 26817870 TI - Association of Head and Neck Cancers in Chronic Osteomyelitis: A National Retrospective Cohort Study. AB - The aim of study is to determine whether chronic osteomyelitis (COM) is linked to an increased risk of head and neck cancer (HNC).We identify 17,033 patients with osteomyelitis and 68,125 subjects without osteomyelitis during 1996 to 2010 periods. Multivariable Cox proportional hazards regression analysis was used to measure the hazard ratio (HR) of head and neck cancer for the osteomyelitis cohort compared with the comparison cohort.A total of 99 patients in the COM and 228 patients in the comparison cohort developed HNC during an average 5.12 years of follow-up period. The incidence rate of HNC in the COM cohort was 1.51-fold (95% confidence interval [CI]: 1.17-1.95) higher than that in the comparison cohort after adjusting gender, age, urbanization level, monthly income, and comorbidities. In subgroup analysis, younger (less than 45 years-old) and patients without comorbidities have greater risks (adjusted HR: 2.29 [95% CI:1.43 3.66] and 1.74 [95% CI:1.28-2.38] respectively).This study results suggested the association between COM and HNC, particularly in younger population and patients without comorbidities. PMID- 26817871 TI - Extrathyroidal Calcitonin Secreting Tumors: Pancreatic Neuroendocrine Tumors in Patients With Multinodular Goiter: Two Case Reports. AB - Calcitonin is the hallmark of medullary thyroid carcinoma. However, extrathyroidal neuroendocrine tumors can also release calcitonin.We report 2 cases of calcitonin-secreting pancreatic tumors found in asymptomatic patients with thyroid nodules referred to our center within 11 months.Case 1: A man initially referred for thyroid nodule characterization was found to have hypercalcitoninemia (>200 pg/mL) during non-neoplastic fine-needle aspiration.Case 2: A woman evaluated for liver metastasis was found to have hypercalcitoninemia and multinodular goiter.Our research emphasizes that marked hypercalcitoninemia in the presence of thyroid nodules is not necessarily due to medullary thyroid carcinoma; awareness of this could avoid unnecessary thyroidectomy. The lack of specific symptoms related to hypercalcitoninemia may be the reason that the prevalence of calcitonin-secreting pancreatic tumors is underestimated. PMID- 26817872 TI - Correlation Between Vision and Cognitive Function in the Elderly: A Cross Sectional Study. AB - The correlation between vision and cognition is not fully understood. Visual impairment in the elderly has been associated with impaired cognitive function, dementia, and Alzheimer disease. The aim was to study the correlation between near visual acuity (VA), refraction, and cognitive state in an elderly population.Subjects >=75 years were enrolled in this cross-sectional study. Refraction and near VA was tested. Cognitive function was evaluated with a version of the mini-mental state examination for the visually impaired (MMSE blind). The eye with better VA and no cataract or refractive surgery was analyzed.One-hundred ninety subjects (81.6 +/- 5.1 years, 69.5% female) were included. Good VA (<=J3) was associated with high MMSE-blind (>17) (OR = 3.18, 95% CI = 1.57-6.43, P = 0.001). This remained significant adjusting for sex, age, and years of education. Wearing reading glasses correlated significantly with high MMSE-blind after adjustment for sex and age (OR = 2.14, 95% CI = 1.16-3.97, P = 0.016), but reached borderline significance after adjustment for education. There was a trend toward correlation between myopia and better MMSE-blind (r = 0.123, P = 0.09, Pearson correlation).Good VA and wearing glasses seem to correlate with better cognitive function. Reading glasses can serve as a protective factor against cognitive deterioration associated with sensory (visual) deprivation in old age. The association between myopia and cognition requires further investigation. PMID- 26817874 TI - Impact of HCV Infection on Diabetes Patients for the Risk of End-Stage Renal Failure. AB - Both diabetes mellitus (DM) and hepatitis C virus infection (HCVI) are associated with chronic kidney disease (CKD). The aim of this study was to evaluate whether HCVI increases the risk of end-stage renal disease (ESRD) in patients with DM.The National Health Insurance Research database of Taiwan was used to conduct this study. After excluding patients with a prior history of CKD, all patients with a first diagnosis of DM from January 1, 2000 to December 31, 2002 were enrolled. The patients who also had HCVI were defined as index cases (HCV group, n = 9787). A comparison cohort at a 1:1 ratio of random incident patients with DM without HCVI matched by age, sex, age at the diagnosis of DM, duration between the diagnosis of DM and the index date, and various comorbidities through propensity score matching were recruited (non-HCV group, n = 9787). The patients were followed until December 31, 2011.The cumulative incidence rate of developing ESRD was significantly higher in the HCV(+) group than in the non-HCV group (P = 0.008). The incidence rate ratio (IRR) for the risk of ESRD was also significantly higher in the HCV(+) group (IRR: 1.44; 95% CI: 1.09-1.89) than in the non-HCV group, especially for those with a younger age (<50 years; IRR: 2.05; 95% CI: 1.22-3.45) and HCVI within 4 years after the diagnosis of DM (IRR: 1.85; 95% CI: 1.16-2.97). After adjusting for comorbidities in multivariate Cox proportional hazard regression analysis, HCVI (HR: 1.47; 95% CI: 1.11-1.93) was an independent factor for developing ESRD in the patients with DM. After starting dialysis for ESRD, the HCV(+) patients had a similar mortality rate to those without HCVI (P = 0.84).HCVI increases the risk of developing ESRD in patients with DM, especially in younger patients and in those who develop HCVI sooner after a diagnosis of DM. PMID- 26817873 TI - Makorin Ring Finger Protein 1 as Adjunctive Marker in Liquid-based Cervical Cytology. AB - To assess the utility of makorin ring finger protein 1 (MKRN1) as a marker of cervical pathology.A PROspective specimen collection and retrospective Blinded Evaluation study was conducted. Liquid-based cytology samples were collected from 187 women, embedding all residuals as cell blocks for immunohistochemical staining of MKRN1 and P16 . Results of liquid-based cervical cytology, immunostained cell block sections, and human papillomavirus (HPV) hybrid capture (with real-time polymerase chain reaction) were analyzed. Clinical outcomes were analyzed overall and in subsets of specimens yielding atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions.Makorin ring finger protein 1 positivity and grades (1-3) of cervical intraepithelial neoplasia (CIN) increased in tandem (CIN1, 32.4%; CIN2, 60.0%; and CIN3, 80.0%), reaching 92.3% in invasive cancer. Sensitivity, specificity, positive predictive value, and negative predictive value in detecting CIN2+ via MKRN1 were 73.8%, 76.8%, 75.6%, and 75.0%, respectively. The performance of liquid-based cytology was poorer by comparison (61.3%, 69.5%, 66.2%, and 64.8%, respectively), and HPV assay (versus MKRN1 immunohistochemical staining) displayed lower specificity (67.7%). Combined HPV + MKRN1 testing proved highest in sensitivity, specificity, positive predictive value, and negative predictive value (71.8%, 85.5%, 82.3%, and 76.5%, respectively), whereas corresponding values for cytology + HPV (60.6%, 81.8%, 75.4%, and 69.2%) and cytology + MKRN1 (58.8%, 84.1%, 78.3%, and 67.7%) were all similar. In instances of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions, the HPV + MKRN1 combination performed best by above measures (100%, 72.7%, 73.9%, and 100%), followed by cytology + MKRN1 (100%, 50.0%, 60.7%, and 100%).Makorin ring finger protein 1 displayed greater sensitivity and specificity than liquid-based cytology and proved more specific than HPV assay. In combination testing, MKRN1 + HPV showed the highest sensitivity and specificity levels. The MKRN1 biomarker may be a useful adjunct in primary cervical cytology screening. PMID- 26817875 TI - Early Life Bereavement and Schizophrenia: A Nationwide Cohort Study in Denmark and Sweden. AB - We aimed to examine whether early life bereavement, as indicator of severe stress, was associated with an increased risk of schizophrenia later in life.Based on population registers, we established a cohort of all children born in Denmark (N = 1 686 416) and Sweden (N = 2 563 659) from 1973 to 1997. Children were categorized as exposed if they lost a first-degree relative during the first 18 years of life. Outcome is the first diagnosis of schizophrenia as either inpatient or outpatient. Log-linear Poisson regression models were used to estimate incidence rate ratios (IRRs).A total of 188,850 children (4.6%) experienced death of a first-degree relative from birth to 18 years of age. Compared with unexposed children, those exposed had overall a 39% higher risk of schizophrenia (= 1.39, 95% CI [confidence interval]: 1.32-1.47). The IRR was particularly high if the family member committed suicide (aIRR = 2.11, 95% CI: 1.90-2.34) or died due to an injury or accident (aIRR = 1.44, 95% CI: 1.27-1.63). The IRR of schizophrenia decreased with increasing child's age at bereavement (P < 0.0001). Children who experienced >1 death during the first 18 years of life (aIRR = 1.79, 95% CI: 1.46-2.19) had a higher risk than those with a single death (aIRR = 1.37, 95% CI: 1.30-1.45).The study suggested that exposure to death of a first-degree relative before 18 years was associated with an increased risk of schizophrenia in later life. The complex mechanisms behind these associations remain to be elucidated. PMID- 26817876 TI - Smoking and Risk of All-cause Deaths in Younger and Older Adults: A Population based Prospective Cohort Study Among Beijing Adults in China. AB - Cigarette smoking is the leading preventable cause of death worldwide. Few studies, however, have examined the modified effects of age on the association between smoking and all-cause mortality.In the current study, the authors estimated the association between smoking and age-specific mortality in adults from Beijing, China. This is a large community-based prospective cohort study comprising of 6209 Beijing adults (aged >=40 years) studied for approximately 8 years (1991-1999). Hazard ratios (HRs) and attributable fractions associated with smoking were estimated by Cox proportional hazard models, adjusting for age, sex, alcohol intake, body mass index, systolic blood pressure, hypertension, and heart rate.The results showed, compared with nonsmokers, the multivariable-adjusted HRs for all-cause mortality were 2.7(95% confidence interval (CI):1.56-4.69) in young adult smokers (40-50 years) and 1.31 (95% CI: 1.13-1.52) in old smokers (>50 years); and the interaction term between smoking and age was significant (P = 0.026). Attributable fractions for all-cause mortality in young and old adults were 63% (95% CI: 41%-85%) and 24% (95% CI: 12%-36%), respectively. The authors estimated multivariate adjusted absolute risk (mortality) by Poisson regression and calculated risk differences and 95% CI by bootstrap estimation. Mortality differences (/10,000 person-years) were 15.99 (95% CI: 15.34-16.64) in the young and 74.61(68.57-80.65) in the old. Compared with current smokers, the HRs of all cause deaths for former smokers in younger and older adults were 0.57 (95% CI: 0.23-1.42) and 0.96 (95% CI: 0.73-1.26), respectively.The results indicate smoking significantly increases the risks of all-cause mortality in both young and old Beijing adults from the relative and absolute risk perspectives. Smoking cessation could also reduce the excess risk of mortality caused by continuing smoking in younger adults compared with older individuals. PMID- 26817877 TI - Clinical Predictors of Long-term Success in Ultrasound-guided High-intensity Focused Ultrasound Ablation Treatment for Adenomyosis: A Retrospective Study. AB - The long-term outcomes of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation treatment for adenomyosis and the relevant factors affecting the durability of symptom relief were assessed in this study.A total of 230 women with adenomyosis who were treated with USgHIFU ablation between January 2007 and December 2013 were retrospectively analyzed. The contrast-enhanced ultrasonography (CEUS) was performed immediately after the treatment to evaluate the ablation effect, and the nonperfused volume (NPV) ratio was then calculated. Regular follow-up was conducted and the visual analog scale (VAS) score was used to assess the changes in dysmenorrhea. The effect of treatment was evaluated after an average follow-up length of 3 months and the factors affecting clinical success and symptom relapse were identified.Of the 230 treated patients, 208 (90.4%) were followed up regularly, with a median follow-up length of 40 months (range, 18-94 months). Mean value of the NPV ratio calculated immediately after the treatment was 57.4 +/- 24.4%. Varying degrees of symptomatic relief of dysmenorrhea based on the VAS scores were observed in 173 (83.2%) patients and 71.0% of the patients were asymptomatic during follow-up. Women with higher NPV ratio (OR = 0.964, 95% CI = 0.947-0.982, P = 0.000) and older age (OR = 0.342, 95% CI = 0.143-0.819, P = 0.016) were more likely to achieve clinical success. Dysmenorrhea recurred in 45 (26%) out of 173 cases; the median recurrence time was 12 months after treatment. The lower BMI (OR = 1.221, 95% CI = 1.079-1.381, P = 0.001) and the higher acoustic power (OR = 0.992, 95% CI = 0.986-0.998, P = 0.007) were associated with less risk of relapse. Twelve of the 14 patients who were retreated by USgHIFU ablation after experiencing dysmenorrhea recurrence achieved clinical success.USgHIFU ablation is an effective uterus-conserving treatment for symptomatic adenomyosis with an acceptable long-term success rate. Higher chance of clinical success can be achieved in patients with larger NPV ratio and older age, whereas higher BMI and lower acoustic power may result in a higher chance of recurrence. These factors are helpful in selecting suitable patients for USgHIFU and in predicting the durability of symptom relief. PMID- 26817878 TI - Assessment of Invasive Breast Cancer Heterogeneity Using Whole-Tumor Magnetic Resonance Imaging Texture Analysis: Correlations With Detailed Pathological Findings. AB - There is no study that investigates the potential correlation between the heterogeneity obtained from texture analysis of medical images and the heterogeneity observed from histopathological findings. We investigated whether texture analysis of magnetic resonance images correlates with histopathological findings.Seventy-five patients with estrogen receptor positive invasive ductal carcinoma who underwent preoperative breast magnetic resonance imaging (MRI) were included. Tumor entropy and uniformity were determined on T2- and contrast enhanced T1-weighted subtraction images under different filter levels. Two pathologists evaluated the detailed histopathological findings of the tumors including tumor cellularity, dominant stroma type, central scar, histologic grade, extensive intraductal component (EIC), and lymphovascular invasion. Entropy and uniformity values on both T2- and contrast-enhanced T1-weighted subtraction images were compared with detailed pathological findings.In a multivariate analysis, entropy significantly increased only on unfiltered T2 weighted images (P = 0.013). Tumor cellularity and predominant stroma did not affect the uniformity or entropy on both T2- and contrast-enhanced T1-weighted subtraction images. High histologic grades showed increased uniformity and decreased entropy on contrast-enhanced T1-weighted subtraction images, whereas the opposite tendency was observed on T2-weighted images. Invasive ductal carcinoma with an EIC or lymphovascular invasion only affected the contrast enhanced T1-weighted subtraction images, through increased uniformity and decreased entropy. The best uniformity results were recorded on T2- and contrast enhanced T1-weighted subtraction images at a filter level of 0.5. Entropy showed the best results at a filter level of 0.5 on contrast-enhanced T1-weighted subtraction images. However, on T2-weighted images, an ideal model was achieved on unfiltered images.MRI texture analysis correlated with pathological tumor heterogeneity. PMID- 26817879 TI - A Randomized, Controlled Safety, and Immunogenicity Trial of the M72/AS01 Candidate Tuberculosis Vaccine in HIV-Positive Indian Adults. AB - Human immunodeficiency virus (HIV)-associated tuberculosis is a major public health threat. We evaluated the safety and immunogenicity of the candidate tuberculosis vaccine M72/AS01 in HIV-positive and HIV-negative Indian adults.Randomized, controlled observer-blind trial (NCT01262976).We assigned 240 adults (1:1:1) to antiretroviral therapy (ART)-stable, ART-naive, or HIV-negative cohorts. Cohorts were randomized 1:1 to receive M72/AS01 or placebo following a 0, 1-month schedule and followed for 12 months (time-point M13). HIV-specific and laboratory safety parameters, adverse events (AEs), and M72-specific T-cell mediated and humoral responses were evaluated.Subjects were predominantly QuantiFERON-negative (60%) and Bacille Calmette-Guerin-vaccinated (73%). Seventy ART-stable, 73 ART-naive, and 60 HIV-negative subjects completed year 1. No vaccine-related serious AEs or ART-regimen adjustments, or clinically relevant effects on laboratory parameters, HIV-1 viral loads or CD4 counts were recorded. Two ART-naive vaccinees died of vaccine-unrelated diseases. M72/AS01 induced polyfunctional M72-specific CD4 T-cell responses (median [interquartile range] at 7 days postdose 2: ART-stable, 0.9% [0.7-1.5]; ART-naive, 0.5% [0.2-1.0]; and HIV negative, 0.6% [0.4-1.1]), persisting at M13 (0.4% [0.2-0.5], 0.09% [0.04-0.2], and 0.1% [0.09-0.2], respectively). Median responses were higher in the ART stable cohort versus ART-naive cohort from day 30 onwards (P <= 0.015). Among HIV positive subjects (irrespective of ART-status), median responses were higher in QuantiFERON-positive versus QuantiFERON-negative subjects up to day 30 (P <= 0.040), but comparable thereafter. Cytokine-expression profiles were comparable between cohorts after dose 2. At M13, M72-specific IgG responses were higher in ART-stable and HIV-negative vaccinees versus ART-naive vaccinees (P <= 0.001).M72/AS01 was well-tolerated and immunogenic in this population of ART stable and ART-naive HIV-positive adults and HIV-negative adults, supporting further clinical evaluation. PMID- 26817880 TI - Treatment of Intercondylar Humeral Fractures With 3D-Printed Osteosynthesis Plates. AB - The aim of the study was to evaluate the efficacy custom 3D-printed osteosynthesis plates in the treatment of intercondylar humeral fractures.Thirteen patients with distal intercondylar humeral fractures were randomized to undergo surgery using either conventional plates (n = 7) or 3D printed plates (n = 6) at our institution from March to October 2014. Both groups were compared in terms of operative time and elbow function at 6 month follow up.All patients were followed-up for a mean of 10.6 months (range: 6-13 months). The 3D-printing group had a significantly shorter mean operative time (70.6 +/- 12.1 min) than the conventional plates group (92.3 +/- 17.4 min). At the last follow-up period, there was no significant difference between groups in the rate of patients with good or excellent elbow function, although the 3D-printing group saw a slightly higher rate of good or excellent evaluations (83.1%) compared to the conventional group (71.4%).Custom 3D printed osteosynthesis plates are safe and effective for the treatment of intercondylar humeral fractures and significantly reduce operative time. PMID- 26817881 TI - Alpha-fetoprotein Level Predicts Recurrence After Transplantation in Hepatocellular Carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the leading causes of liver transplantation. In an attempt to predict their recurrence after liver transplantation, evaluation of tumor number and size, degree of histologic differentiation, and the presence of vascular invasion already have their importance established. In this context, the role of biologic markers such as alpha-fetoprotein (AFP) is still not clear. This retrospective cross-sectional study analyzed the AFP relationship with recurrence of HCC after orthotopic liver transplantation.The current study retrospectively analyzed data from 206 patients with a histopathologic confirmed HCC between 1997 and 2010.The overall survival rates at 1, 3, 5, and 14 years were 78.6%, 65.4%, 60.5%, and 38.7%, respectively. The frequency of recurrence was 15.5%, and recurrence was significantly associated with a lower survival rate (P < 0.001). No association was observed between survival and AFP level (P = 0.153). A correlation, however, was found between tumor recurrence and AFP level (P = 0.002). Univariate analysis of risk factors for recurrence revealed that an AFP level greater than 200 ng/mL, the number of tumors, the degree of cellular differentiation, and the presence of vascular invasion or satellite nodules were associated with relapse. By multivariate analysis, only an AFP level greater than 200 ng/mL remained as a risk factor.Although an elevated AFP level did not correlate with survival in HCC patients undergoing orthotopic liver transplantation, a high AFP level was associated with a 3.32-folds increase in the probability of HCC recurrence. PMID- 26817882 TI - No Evidence of an Association Between Efavirenz Exposure and Suicidality Among HIV Patients Initiating Antiretroviral Therapy in a Retrospective Cohort Study of Real World Data. AB - Recently, published studies have reported conflicting results regarding the association between efavirenz exposure and the risk of suicidality among patients with human immunodeficiency virus. The objective of this analysis was to compare the rate of suicidality among patients initiating efavirenz-containing versus efavirenz-free antiretroviral (ARV) regimens.This retrospective cohort study used US administrative claims data for commercially and Medicaid-insured individuals for the years 2006 to 2013. ARV-naive patients aged >=12 years initiating an efavirenz-containing or efavirenz-free ARV regimen with >=6 months of continuous insurance enrollment prior to ARV initiation were selected. The primary outcome was suicidality, defined as the occurrence of any medical claim with a diagnosis code for suicidal ideation or an inpatient or emergency department medical claim for suicide attempt. Unadjusted incidence rates were calculated and propensity score-adjusted hazard ratios were estimated to account for differences in patient characteristics.There were 19,983 patients (efavirenz-containing, n = 11,187; efavirenz-free, n = 8796) in the commercial database and 5154 patients (efavirenz containing, n = 2224; efavirenz-free, n = 2930) in the Medicaid database. Unadjusted incidence rates (95% confidence interval [CI]) of suicidality per 1000 person-years were: commercial, efavirenz-containing (3.3 [2.4-4.4]), efavirenz free (4.0 [2.7-5.8]); Medicaid, efavirenz-containing (25.7 [18.8-34.4]), efavirenz-free (40.6 [31.9-50.9]). In propensity score-adjusted analyses, efavirenz use was not associated with suicidality: adjusted hazard ratio (95% CI) of suicidality compared with efavirenz-free regimen, commercial, 1.029 (0.636 1.665); Medicaid, 0.902 (0.617-1.319).This analysis found no conclusive evidence of an increased risk of suicidality among patients initiating an efavirenz containing ARV regimen. However, channeling bias may exist even after adjusting for measured patient characteristics. PMID- 26817884 TI - Pyogenic Liver Abscess is Associated With Increased Risk of Acute Kidney Injury: A Nationwide Population-Based Cohort Study. AB - The aim of this large population-based cohort study was to determine whether pyogenic liver abscess (PLA) is associated with the risk of acute kidney injury (AKI).A total of 31,815 patients aged 20 years or older diagnosed with PLA for the first time during hospitalization between 2000 and 2011 were included in a PLA cohort, and 127,620 age- and sex-matched patients without PLA were included in a non-PLA cohort. The incidence and the risk of the first attack of AKI at the end of 2011 were measured. Cox proportional hazard regression models were used to analyze the risk of AKI.In mean follow-up periods of 4.36 and 4.94 years for the PLA and non-PLA cohorts, respectively, the overall incidence of AKI was 1.51-fold greater in the PLA cohort than in the non-PLA cohort (9.25 vs 6.11 events per 1000 person-years; 95% confidence intervals [CIs] = 1.42-1.61). After we controlled for potential confounding factors, the adjusted hazard ratio (aHR) of AKI was 1.36 (95% CIs = 1.27-1.46) for the PLA cohort compared with the non-PLA cohort. Moreover, among patients without comorbidities, the risk of AKI remained higher in the PLA cohort compared with the non-PLA cohort (aHR: 1.91, 95% CIs = 1.59-2.29).This study suggests that PLA associates with an increased risk of AKI. Clinicians should be aware of the potential risk of AKI after diagnosis of PLA. PMID- 26817883 TI - Predictors of Inpatient Mortality and Resource Utilization for the Elderly Patients With Chronic Hepatitis C (CH-C) in the United States. AB - New incidents of chronic hepatitis C (CH-C) have stabilized yet the full impact of CH-C is not realized.Assess inpatient mortality and resource utilization for CH-C patients hospitalized in the United States.Adult CH-C patients were identified from The National Inpatient Sample (NIS) 2005 to 2009 database using the International Classification of Disease, Ninth Revision (ICD-9) diagnosis codes (070.51, 070.54, 070.70, 070.71, 070.41, and 070.44) also used to identify comorbidities.324,823 hospitalized CH-C patients were identified. Of these, 13.63% (N = 44,288) were older than 65. The rate of hospitalization for the elderly cohort steadily increased over the study period with Medicare as the payer for the majority (86%). This cohort had higher inpatient charges, approximately a half day longer hospital stay (P < 0.001) and more moderate or severe illness. During the index hospitalization, older CH-C patients were twice more likely to die than the younger age-group (5% versus 2%, P < 0.001). In the adjusted model, older age (OR: 1.02 [95% CI, 1.02-1.03]), severity of illness (OR: 12.06 [95% CI, 10.68-13.62]), and number of diagnoses (OR: 1.10 [95% CI, 1.09-1.11]) were associated with higher in-hospital mortality; severity of illness and having private insurance were significantly associated with charge per hospital stay (P < 0.001).The number of CH-C patients 65 and older increased due to the aging of the baby boomer population. Early treatment of CH-C patients with highly effective, well-tolerated, new anti-HCV regimens may prevent this significant societal burden. PMID- 26817885 TI - Primary Cutaneous Nocardiosis in a Patient With Nephrotic Syndrome: A Case Report and Review of the Literature. AB - Nocardia infection is not common in clinical practice and most cases occur as an opportunistic infection in immunocompromised patients.We report a case of primary cutaneous nocardiosis characterized by multiple subcutaneous abscesses due to Nocardia brasiliensis in a patient with nephrotic syndrome undergoing long-term corticosteroid therapy. The patient was diagnosed with nephrotic syndrome 9 months ago, and mesangial proliferative glomerulonephritis was confirmed by renal biopsy. Subsequently, his renal disease was stable under low-dose methylprednisolone (8 mg/d). All of the pus cultures, which were aspirated from 5 different complete abscesses, presented Nocardia. Gene sequencing confirmed that they were all N. brasiliensis. The patient was cured by surgical drainage and a combination of linezolid and Trimethoprim-Sulfamethoxazole.The case highlights that even during the period of maintenance therapy with low-dose corticosteroid agents, an opportunistic infection still could occur in patients with nephrotic syndrome. PMID- 26817886 TI - Influence of Weight-Age Normalization on Glomerular Filtration Rate Values of Renal Patients: A STROBE-Compliant Article. AB - To explore whether weight-age (W-A) could be applied in clinical practice, this study was designed to verify the normalization ability of W-A by the data from another medical center, and to access the influence of the normalization on glomerular filtration rate (GFR) values in renal patients.Both plasma clearance (pGFR) and camera-based (gGFR), which were separately scaled to W-A and body surface area (BSA), were measured for patients with diffuse renal diseases. The patients (n = 298) were stratified according to the Chinese body mass index (BMI) criteria and were staged according to the Kidney Disease Outcome Quality Initiatives guideline based on gGFR and pGFR separately.The indices of intraclass correlation coefficient (ICC), concordance correlation coefficient (CCC), and ratio of residual standard deviation to pooled standard deviation (RSD/PSD) suggested that, for all patients and each BMI stratum, W-A was obviously better than BSA in scaling GFR. Both under pGFR or gGFR renal stages, only small amount of the patients encountered stage migrations from BSA to W-A scaled stages. The differences between any 2 of the unscaled, BSA scaled, and W-A scaled gGFR (or pGFR) were not obviously changed. Additionally, in some strata, W-A normalization is better than BSA normalization in decreasing the median bias between pGFR and gGFR.W-A is better than BSA in scaling GFR without obvious modifying GFR values and can be applied in routine clinical practice. PMID- 26817887 TI - Differences Between Women and Men in Phase I Cardiac Rehabilitation After Acute Myocardial Infarction: A Nationwide Population-Based Analysis. AB - Although numerous studies have investigated gender-related differences in patients who have had an acute myocardial infarction (AMI), few studies have examined the gender-related differences among inpatients receiving Phase I inpatient cardiac rehabilitation following AMI.Using data from the Taiwan National Health Insurance Research Database, this study analyzed 6713 adult patients who received inpatient cardiac rehabilitation following AMI between 2002 and 2011. The differences in comorbidity, medical service use, and prognosis between the male and female patients were analyzed to determine whether the comorbidities affecting their prognoses differed.Female patients accounted for 23.18% of the sample, had a higher average age, and exhibited severe comorbidities; furthermore, they had significantly more days of hospitalization and days in an intensive care unit than did male patients. The gender-related differences in hospital mortality rate and 30-day mortality rate were nonsignificant, but female patients exhibited a significantly higher 1-year mortality rate. Moreover, the risk for 1-year mortality was higher among female patients with moderate or severe renal disease (odds ratio: 1.94, 95% confidence interval: 1.29-2.92) than among their male counterparts. However, the 1-year mortality rate for the female patients did not increase after all risk factors were adjusted.Gender-related differences in age, comorbidity, and prognosis were confirmed in AMI patients receiving Phase I inpatient cardiac rehabilitation. In addition, gender-related differences were observed in the comorbidity risk factors affecting prognosis. However, being female did not affect the prognosis. PMID- 26817888 TI - Relationship Between Sarcopenia and Albuminuria: The 2011 Korea National Health and Nutrition Examination Survey. AB - Studies have shown that albuminuria, obesity, and sarcopenia may share pathophysiological processes related to cardiovascular disease risk. Their direct relationships, however, have not been examined. This study investigated the association between albuminuria and sarcopenia in a representative fraction of the Korean population.Of the 10,589 people who participated in the 2011 Korea National Health and Nutrition Examination Survey, 2158 participants aged over 19 years had been tested for albumin-to-creatinine ratio and for body composition data using dual-energy x-ray absorptiometry. Albuminuria was defined as an albumin-to-creatinine ratio >=30 mg/g. Sarcopenia was defined as a skeletal muscle index (SMI) (SMI (%) = total appendicular skeletal muscle mass [kg]/weight [kg] * 100) of less than 1 standard deviation (SD) (grade 1) or 2 SD (grade 2) below the sex-specific mean for a younger reference group.The prevalence of albuminuria was higher in those with grade 2 sarcopenia than in those with a normal SMI or grade 1 sarcopenia (33.3% versus 8.4% and 8.9%; P < 0.001). Conversely, grade 2 sarcopenia was also more prevalent in participants with albuminuria than in those with the upper tertile of normoalbuminuria. In addition, multiple logistic regression analysis showed the odds ratio for albuminuria risk in the grade 2 sarcopenia group was 2.93 (95% confidence interval [CI], 1.46-5.88), compared with normal SMI after adjusting for potential confounding factors, including the presence of obesity, diabetes, and hypertension. Moreover, individuals with albuminuria had an odds ratio of 3.39 (95% [confidence interval], 1.38-8.37) for grade 2 sarcopenia compared with those in the lowest tertile of normoalbuminuria.This is the first study to demonstrate that individuals with sarcopenia exhibited increased risk of albuminuria and vice versa. PMID- 26817889 TI - Survival Benefits With Artificial Liver Support System for Acute-on-Chronic Liver Failure: A Time Series-Based Meta-Analysis. AB - The artificial liver support system (ALSS) offers the potential to improve the prognosis of patients with acute-on-chronic liver failure (ACLF). However, the literature has been inconsistent on its survival benefits. We aimed to conduct a time series-based meta-analysis of randomized clinical trials (RCTs) and observational studies which examined differences in mortality in ACLF patients treated with ALSS or not.MEDLINE, EMBASE, OVID, and COCHRANE library database were systemically searched up to December 2014. Quality of included studies was evaluated using the Jadad score. The outcome measure was mortality at different follow-up endpoints. Odds ratios (ORs) and survival curve data were pooled for analysis.Ten studies, 7 RCTs, and 3 controlled cohorts were enrolled, involving a total of 1682 ACLF patients, among whom 842 were treated with ALSS. ALSS was found to reduce the risk of short-term (1-month and 3-month) mortality for patients with ACLF by nearly 30%. Randomized trials and observational studies provided good internal and external validity respectively. The combined Kaplan Meier curves showed a consistent pattern of findings. Meta-analysis also suggested that ALSS might reduce medium-term (6-month and 1-year) mortality risk by 30% and long-term (3-year) mortality risk by 50% in ACLF patients.ALSS therapy could reduce short-term mortality in patients with ACLF. Meanwhile, its impacts on medium- and long-term survival seem to be promising but remained inconclusive. Clinical utility of this system for survival benefit may be implied. PMID- 26817890 TI - Predictors for Reconstruction and Mood Disorder Associated With Reconstruction in Patients With Breast Cancer and Mastectomy: A Retrospective Cohort Study. AB - This study used Taiwan's National Health Insurance medical claims to investigate the predictors for operative modes chosen by early-stage breast cancer patients; as well as to assess whether operative modes are associated with risk of mood disorder. We included 36,377 patients with breast cancer who received surgery between 2000 and 2008, and were followed to the end of 2010; they were further classified into 3 groups: mastectomy alone (n = 34,900), along with early reconstruction (n = 1080), and along with delayed reconstruction (n = 397). The results showed that age, insurance premium, urbanization level, and postsurgery chemotherapy and radiotherapy were all significant predictors for the selection of operative modes. Breast cancer patients with mastectomy alone, early reconstruction, and delayed reconstruction showed a cumulative incidence rate of mood disorder of 36.90%, 41.56%, and 33.89%, respectively. The multiple cox proportional model further revealed that early (hazard ratio [HR] = 1.06, 95% confidence interval (CI) = 0.93-1.21) and delayed (HR = 1.17, 95% CI = 0.96-1.42) reconstruction were associated with a slightly higher but insignificant risk of mood disorder, as compared to the patients received no reconstruction. PMID- 26817891 TI - Death Does Matter--Cancer Risk in Patients With End-Stage Renal Disease: A Nationwide Population-Based Study With Competing Risk Analyses. AB - Patients with end-stage renal disease (ESRD) have a high mortality rate. We hypothesized that not accounting for death as a competing risk overestimates the event rate caused by ESRD. Thus, we examined the cancer risk for patients with ESRD (ESRD) after death as a competing risk event had been adjusted for. Patients with newly diagnosed ESRD (n = 64,299) between 1999 and 2007, together with age- and sex-matched controls without ESRD (ESRD) (n = 128,592) were enrolled (1:2). In a Cox proportional hazards model that included death as a competing risk, ESRD patients in Taiwan had a lower overall incidence (subdistribution hazard ratio [sdHR] = 1.29) of cancer than did ESRD patients in a Cox model that did not include death as a competing risk (HR = 1.70). After competing mortality had been adjusted for, ESRD patients >=70 (sdHR = 0.82) and ESRD patients on long-term dialysis (> 5 follow-up years, sdHR = 0.62), had a lower risk for developing cancer than did ESRD patients. This finding supported our hypothesis that standard survival analyses overestimate the event rate, especially when the mortality rate is high. It also showed that ESRD patients, when they grow older, were far less likely to develop cancer and far more likely to die because of underlying illnesses that might also affect the risk of death because of ESRD. PMID- 26817893 TI - Assessment of the Reporting Quality of Placebo-controlled Randomized Trials on the Treatment of Type 2 Diabetes With Traditional Chinese Medicine in Mainland China: A PRISMA-Compliant Systematic Review. AB - Placebo-controlled randomized trials are often used to evaluate the absolute effect of new treatments and are considered gold standard for clinical trials. No studies, however, have yet been conducted evaluating the reporting quality of placebo-controlled randomized trials. The current study aims to assess the reporting quality of placebo-controlled randomized trials on treatment of diabetes with Traditional Chinese Medicine (TCM) in Mainland China and to provide recommendations for improvements.China National Knowledge Infrastructure database, Wanfang database, China Biology Medicine database, and VIP database were searched for placebo-controlled randomized trials on treatment of diabetes with TCM. Review, animal experiment, and randomized controlled trials without placebo control were excluded. According to Consolidated Standards of Reporting Trials (CONSORT) 2010 checklists items, each item was given a yes or no depending on whether it was reported or not.A total of 68 articles were included. The reporting percentage in each article ranged from 24.3% to 73%, and 30.9% articles reported more than 50% of the items. Seven of the 37 items were reported more than 90% of the items, whereas 7 items were not mentioned at all. The average reporting for "title and abstract," "introduction," "methods," "results," "discussion," and "other information" was 43.4%, 78.7%, 40.1%, 49.9%, 71.1%, and 17.2%, respectively. The percentage of each section had increased after 2010. In addition, the reporting of multiple study centers, funding, placebo species, informed consent forms, and ethical approvals were 14.7%, 50%, 36.85%, 33.8%, and 4.4%, respectively.Although a scoring system was created according to the CONSORT 2010 checklist, it was not designed as an assessment tool. According to CONSORT 2010, the reporting quality of placebo-controlled randomized trials on the treatment of diabetes with TCM improved after 2010. Future improvements, however, are still needed, particularly in methods sections. PMID- 26817892 TI - Pentraxin 3 Is Closely Associated With Tubulointerstitial Injury in Lupus Nephritis: A Large Multicenter Cross-Sectional Study. AB - Lupus nephritis always elicits immune inflammatory tissue damages in kidney. Pentraxin 3 (PTX3), mainly produced at inflammatory sites, is known to be involved in the regulation of the innate immunity system. The aim of this study was to investigate the serum and urine levels of PTX3, and the expression of PTX3 in renal tissues in lupus nephritis patients from a large Chinese cohort.The study used cross-sectional survey and 288 active lupus nephritis patients, including discovery cohort and validation cohort, 115 systemic lupus erythematosus (SLE) patients without clinical renal involvement and 46 healthy controls were enrolled. Serum and urine PTX3 were screened by enzyme-linked immunosorbent assay (ELISA). The renal deposition of PTX3 was detected by immunohistochemistry and immunofluorescence.The average level of serum PTX3 in the discovery cohort of lupus nephritis was significantly higher than that in nonrenal involvement SLE group and normal controls (P < 0.001, P < 0.001, respectively), which was confirmed by the validation cohort. Serum PTX3 levels of 15 lupus nephritis patients in remission decreased significantly compared with that in active phase. Serum PTX3 levels were significantly higher in patients with hematuria (P = 0.014), leucocyturia (P = 0.002), acute renal failure (P = 0.001), and nephrotic syndrome (P = 0.036). There were significant correlations between serum PTX3 levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, serum creatinine value, renal pathological activity indices, and serum complement 3 (C3) in active lupus nephritis patients. The urinary PTX3 levels were significantly higher in active lupus nephritis patients compared with patients in remission and normal controls (P = 0.011, P = 0.008, respectively). There were significant associations between urinary PTX3 levels and multiple indices of tubulointerstitial lesions, including urinary KIM-1 (r = 0.368, P = 0.016), neutrophil gelatinase-associated lipocalin (NGAL) (r = 0.320, P = 0.039), microalbumin (r = 0.621, P = 0.003), transferring (r = 0.451, P = 0.040) levels and renal pathological indices scores, especially interstitial inflammation (r = 0.349, P = 0.025) in active lupus nephritis patients. A significant correlation was found between serum and urine PTX3 levels (r = 0.431, P = 0.006). PTX3 staining was mainly observed in tubulointerstitial areas of patients with lupus nephritis, and immunofluorescence study showed that PTX3 could colocalize with fibroblast in interstitium.Circulating and local PTX3 levels were significantly increased in patients with active lupus nephritis and might be a biomarker for the disease progression, especially of tubulointerstitial injury. PMID- 26817894 TI - Inverted Internal Limiting Membrane Flap For Large Traumatic Macular Holes. AB - The aim of the study was to assess the role of inverted internal limiting membrane flap as a treatment option for large traumatic macular holes.This is a prospective noncomparative study in which 12 eyes with large traumatic macular holes (basal diameter of 1300-2800 MUm) since 3 to 6 months were subjected to standard 23-gauge vitrectomy with removal of the posterior hyaloid, brilliant blue G (BBG)-assisted internal limiting membrane peeling in a circular fashion keeping it attached to the edge of the hole to create a flap. At the end of the surgery, air fluid exchange was done with inversion of the internal limiting membrane flap inside the macular hole using the soft tipped cannula and sulfur hexafluoride 20% as tamponade. The main follow-up measures are the best corrected visual acuity and the optical coherence tomography for 6 to 9 months.All the included eyes had a closed hole from the first week postoperative and along the follow-up period (6-9 months). The best corrected visual acuity improved from 20/2000 to 20/200 with a median of 20/400 preoperatively to 20/400 to 20/50 with a median of 20/100 at the end of follow-up period.Inverted internal limiting membrane flap is a good adjuvant to standard vitrectomy in the management of large traumatic macular holes that led to the 100% closure rate and improvement of best corrected visual acuity. PMID- 26817895 TI - Selective Retina Therapy in Patients With Chronic Central Serous Chorioretinopathy: A Pilot Study. AB - We evaluated visual outcomes, changes of maximum macular thickness (MMT) and subretinal fluid (SRF), and safety in patients with chronic central serous chorioretinopathy (CSC) after treatment with selective retina therapy (SRT). Retrospective cohort study of patients with chronic CSC presenting to a university-based hospital from January 2014 through January 2015 was conducted. A total of 12 eyes of 12 patients with chronic CSC lasting for at least 3 months was recruited. The follow-up period ranged from 3 to 12 months. Following evaluation of test spots at temporal arcades, SRT (Q-switched neodymium-doped yttrium lithium fluoride [Nd:YLF] laser; wavelength, 527 nm, pulse duration, 1.7 microsececond) was applied to the surrounding areas of leakage observed on fluorescein angiogram and/or pigment epithelial detachment (PED). Changes in best correct visual acuity (BCVA), MMT, and SRF and macular sensitivity (MS) by microperimetry (MP) were evaluated. Eyes received treatment in a mean of 3.83 spots at the pulse energy of 65 to 90 MUJ. Mean BCVA (logMAR) improved from 0.23 +/- 0.12 at baseline to 0.14 +/- 0.13 at 3 months. MMT decreased from 341.4 +/- 85.5 MUm at baseline to 236.0 +/- 57.9 MUm at 3 months. SRF completely resolved in 75% (9 eyes) at 3 months. Large PEDs (2 eyes) were flattened at 3 months. Retreatment was performed in 4 eyes. MP showed no evidence of scotoma around SRT treated lesions. SRT treatment targeting the surrounding area of leakage point showed favorable visual and structural outcomes in chronic CSC patients without the risk of scotoma. PMID- 26817896 TI - Mesopancreatic Stromal Clearance Defines Curative Resection of Pancreatic Head Cancer and Can Be Predicted Preoperatively by Radiologic Parameters: A Retrospective Study. AB - Pancreatic ductal adenocarcinoma (PDAC) is characterized by a strong fibrotic stromal reaction and diffuse growth pattern. Peritumoral fibrosis is often evident during surgery but only distinguishable from tumor by microscopic examination. The aim of this study was to investigate the role of clearance of fibrotic stromal reaction at the mesopancreatic resection margin as a criterion for radical resection and preoperative assessment of resectability.Mesopancreatic stromal clearance status (S-status) was defined as the presence or absence (S+/S0) of fibrotic stromal reaction at the mesopancreatic resection margin. Detailed retrospective clinicopathologic re-evaluation of margin status and preoperative cross-sectional imaging was performed in a cohort of 91 patients operated for pancreatic head PDAC from 2001 to 2011.Conventional margin positive resection (R+, tumor cells directly at the margin) was found in 36%. However, S status further divided the margin negative (R0) group into patients with median survival of 14 months versus 31 months (S+ versus S0, P = 0.005). Overall rate of S+ was 53%. S-status and lymph node ratio constituted the only independent predictors of survival. Stranding of the superior mesenteric artery fat sheath was the only independent radiologic predictor of S+ resection, and achieved a 71% correct prediction of S-status.Mesopancreatic stromal clearance is a major determinant of curative resection in PDAC, and preoperative prediction by cross sectional imaging is possible, setting the basis for a new definition of borderline resectability. PMID- 26817897 TI - Association of Traditional Chinese Medicine Therapy and the Risk of Vascular Complications in Patients With Type II Diabetes Mellitus: A Nationwide, Retrospective, Taiwanese-Registry, Cohort Study. AB - With an increasing use of traditional Chinese medicine (TCM) in type 2 diabetes mellitus (T2DM), evidence of long-term benefit with adjunctive TCM treatment is limited. This study investigated whether the concurrent TCM treatment reduces the risk of vascular complications in T2DM patients by using a large population from National Health Insurance Research Database (NHIRD).We identified 33,457 adult patients with newly diagnosed T2DM using anti-diabetic agents from a random sample of one million beneficiaries in the NHIRD between January 1, 2000 and December 31, 2011. We recruited 1049 TCM users (received TCM over 30 days with a diagnosis of T2DM) and randomly selected 4092 controls as the non-TCM cohort at a ratio of 1:4 frequency-matched by age, sex, hypertension, hyperlipidemia, and index year. We investigated the prescription pattern of TCM and conducted a Cox proportional hazards regression to calculate the hazard ratios (HRs) of stroke, chronic kidney diseases (CKD), and diabetic foot between the 2 cohorts.In the TCM cohort, the prescription pattern of TCM was different between insulin and noninsulin patients. The most common herbs were Dan-Shen (Radix Salviae Miltiorrhizae) in noninsulin group and Da-Huang (Radix et Rhizoma Rhei) in insulin group. The most common formulae were Liu-Wei-Di-Huang-Wan in noninsulin group and Yu-Quan-Wan in insulin group. Although no significant reduction in the hazard ratio of CKD and diabetic foot, the incidence rate of stroke was 7.19 per 1000 person-years in the TCM cohort and 10.66 per 1000 person-years in the control cohort, respectively. After adjustment of age, sex, hypertension, hyperlipidemia, and antidiabetes agent use (including sulfonylureas, alpha glucosidase, metformin, meglitinide, thiazolidinediones, and insulin), TCM cohorts were found to have a 33% decreased risk of stroke (95% CI = 0.46-0.97; P < 0.05).This population-based retrospective study showed that the complementary TCM therapy might associate with the decreased risk of stroke in T2DM, suggesting TCM as an adjunctive therapy for T2DM to prevent subsequent stroke. PMID- 26817898 TI - Unusual Endoscopic Findings in Children: Esophageal and Gastric Polyps: Three Cases Report. AB - Isolated polyps of the upper digestive tract are rarely diagnosed in children, being usually an incidental finding during endoscopic exploration.The diagnostic, therapy, and outcome of these lesions are based on endoscopy and pathology.In a 5 year period, clinical features, topography, size, pathology, therapeutics, and progression of esophagogastric polyps founded in children addressed to our pediatric gastroenterology unit were studied.The authors encountered 3 lesions in teenagers aged 13 to 17 years two males (2M), from a total number of 2140 upper digestive endoscopies (0.14%). All patients presented with pirosis, epigastric pain, and vomits; one of the children had end-stage renal disease and Kabuki syndrome. Endoscopic and pathologic findings were 2 esophageal polyps, an inflammatory one, and another containing goblet cells and a double-headed hyperplastic gastric polyp. Two patients received proton pump inhibitors without any improvement in subsequent endoscopic evaluations.The difficulties related to age group, underlying conditions, debatable response to acid suppression, and limited experience in pediatric therapeutic endoscopy selected significantly the effectiveness of treatment.The rarity of these lesions requires an individualized management, the endoscopic diagnostic, and therapeutic gesture depending on the symptoms, type, location, comorbidities, and team experience. PMID- 26817899 TI - Arthroscopic-assisted Arthrodesis of the Knee Joint With the Ilizarov Technique: A Case Report and Literature Review. AB - Arthrodesis of the knee joint is a mainly a salvage surgical procedure performed in cases of infected total knee arthroplasty, tumor, failed knee arthroplasty or posttraumatic complication.The authors report the case of 18-year-old male with posttraumatic complication of left knee because of motorbike accident 1 year before. He was treated immediately after the injury in the local Department of Orthopaedics and Traumatology. The examination in the day of admission to our department revealed deformation of the left knee, massive scar tissue adhesions to the proximal tibial bone and multidirectional instability of the knee. The plain radiographs showed complete lack of lateral compartment of the knee joint and patella. The patient complained of severe instability and pain of the knee and a consecutive loss of supporting function of his left limb. The authors decided to perform an arthroscopic-assisted fusion of the knee with Ilizarov external fixator because of massive scar tissue in the knee region and the prior knee infection.In the final follow-up after 54 months a complete bone fusion, good functional and clinical outcome were obtained.This case provides a significant contribution to the development and application of low-invasive techniques in large and extensive surgical procedures in orthopedics and traumatology. Moreover, in this case fixation of knee joint was crucial for providing good conditions for the regeneration of damaged peroneal nerve. PMID- 26817901 TI - Asthma Is Associated With a Subsequent Risk of Peripheral Artery Disease: A Longitudinal Population-Based Study. AB - Asthma has been associated with the atherosclerosis risk, but not clear of peripheral artery disease (PAD). We attempted to examine the risk of PAD in patients with asthma.From the insurance claims data of Taiwan, we identified 28,158 newly diagnosed asthma patients in 2000 to 2005 and 56,316 persons without asthma randomly selected into the comparison cohort, frequency matched by sex, age, and the date of diagnosis. Both cohorts were followed up until the end of 2011 to estimate the incident PAD. Adjusted hazard ratios (aHRs) of PAD were estimated using the Cox proportional hazards model after controlling for sex, age, and comorbidities.The incidence of PAD was 1.46 times higher in the asthma cohort than in the comparison cohort, with an aHR of 1.34 [95% confidence interval (CI) = 1.24-1.45]. Incidence of PAD was higher in men, the aged, and those with comorbidities in both cohorts. The aHRs of PAD remained significant for the asthma cohort in all subgroups of sex, age, and the presence of comorbidity. The aHRs of PAD were 14.1 (95% CI = 8.18-24.5) in asthma patients with multiple emergency visits and 22.3 (95% CI = 15.6-31.9) for those with multiple hospitalizations.Although smoking is a potential confounding factor, this study suggests patients with asthma have a significantly higher risk of developing PAD than the general population. The results also support the notion that poor control of asthma status is a key factor in subsequent PAD development. PMID- 26817900 TI - Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Prostate Cancer: A Systematic Review and Meta-analysis. AB - Inflammation is increasingly reported to be associated with the prognosis of patients with cancers. And the prognostic role of neutrophil-to-lymphocyte ratio (NLR) in patients with prostate cancer (PCa) remains inconsistent. Therefore, we conducted this systematic review and meta-analysis to obtain a more reliable assessment of prognostic significance of NLR in PCa.A comprehensive literature research regarding the association of NLR and prognosis of PCa was performed through PubMed, Embase, Cochrane Central, and Web of Science. The hazard ratios (HRs) and its 95% confidence intervals (CIs) for overall survival (OS), progression-free survival, or recurrence-free survival were extracted and pooled using fix-effects model or random-effects model.A total of 14 studies that met our criterion were included in this meta-analysis. Our pooled results demonstrated that elevated NLR was not significantly associated with the poor OS (HR = 1.45; 95% CI 0.77-2.71; P = 0.248) or recurrence-free survival (HR = 1.34; 95% CI 0.89-2.02; P = 0.155) of patients with localized PCa. Although elevated NLR predicted poorer OS (HR = 1.57; 95% CI 1.41-1.74; P < 0.001) and progression free survival (HR = 1.97; 95% CI 1.28-3.04; P = 0.002) of patients with metastatic castration resistant prostate cancer (mCRPC).Elevated NLR is a strong indicator of poorer prognosis of patients with mCRPC, whereas the NLR is not significantly associated with prognosis of patients with localized PCa. Therefore, NLR could be used in patients with mCRPC for risk stratification and decision making of individual treatment. PMID- 26817902 TI - Impact of Breast Cancer Subtype Defined by Immunohistochemistry Hormone Receptor and HER2 Status on the Incidence of Immediate Postmastectomy Reconstruction. AB - Immediate postmastectomy reconstruction has become an increasingly popular choice for breast cancer patients recently. However, whether molecular subtype of cancer impacts the incidence of breast reconstruction is unclear. We aimed to investigate the association between breast cancer subtype defined by immunohistochemistry hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status and recent rates of immediate postmastectomy reconstruction in the United States.The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was used to evaluate stage I-III breast cancer patients with different subtypes who underwent either mastectomy alone or mastectomy plus reconstruction between 2010 and 2012. Univariate and multivariate analyses were conducted to identify factors influencing the incidence of immediate reconstruction.Of 47,123 women included, 33.1% (10,712/32,376) of HR+/HER2-, 33.1% (1912/5768) of HR+/HER2+, 29.6% (850/2875) of HR-/HER2+, and 27.7% (1689/6104) of triple negative breast cancer patients received immediate breast reconstruction (chi-square test, P < 0.001), respectively. Thus, HER2-overexpressing and triple negative breast cancer patients received significantly less breast reconstruction. After adjusting for demographic, socioeconomic, geographic, or clinicopathologic factors, HER2 overexpressing (OR 0.896, 95% CI 0.817-0.984) and triple negative (OR 0.806, 95% CI 0.751-0.866) breast cancer patients remained less likely to undergo immediate postmastectomy reconstruction compared with HR+/HER2- or HR+/HER2+ patients. No significant difference was found in the type of reconstruction among different subtypes. Subgroup analysis showed that the difference of breast reconstruction rates among distinct subtypes varied with different grade and stage groups, and the association between breast cancer subtype and the reconstruction rate was not significant in low grade and early stage patients.This population-based study determined that breast cancer subtype was an independent predictor for the utilization of immediate postmastectomy reconstruction. Patients with HER2 overexpressing or triple negative breast cancer subtype that has relatively higher risk of local recurrence, were less likely to receive immediate breast reconstruction than those with luminal tumors. Further studies are needed to disclose more underlying reasons of different reconstruction incidences for distinct subtypes of breast cancer. PMID- 26817903 TI - Postoperative Adverse Outcomes in Patients With Asthma: A Nationwide Population based Cohort Study. AB - Outcome after surgery in patients with asthma remains unknown. The purpose of this study is to investigate postoperative major complications and mortality in surgical patients with asthma.Using reimbursement claims from the Taiwan National Health Insurance Research Database, the authors identified 24,109 surgical patients with preoperative asthma and 24,109 nonasthma patients undergoing major surgeries using matching procedure with propensity score by sociodemographics, coexisting medical conditions, and surgical characteristics. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for 30-day postoperative complications and mortality associated with asthma were analyzed in the multivariate logistic regressions.Asthma increased postoperative pneumonia (OR 1.48; 95% CI 1.34-1.64), septicemia (OR 1.11; 95% CI 1.02-1.21), and urinary tract infection (OR 1.17; 95% CI 1.09-1.26). Preoperative emergency care for asthma was significantly associated with postoperative 30-day in-hospital mortality, with an OR of 1.84 (95% CI 1.11-3.04). Preoperative emergency service, hospitalizations, admission to intensive care unit, and systemic use of corticosteroids for asthma were also associated with higher postoperative complication rates for asthmatic patients.Postoperative complications and mortality were significantly increased in asthmatic patients. We suggest urgent efforts to revise protocols for asthma patients' perioperative care. PMID- 26817904 TI - Increased Long-Term Risk of Dementia in Patients With Carbon Monoxide Poisoning: A Population-Based Study. AB - Carbon monoxide (CO) poisoning may cause toxicity of the central nervous system and heart. However, the association between CO poisoning and long-term dementia risk remains unestablished. We investigated the incidence of dementia in patients with CO poisoning in Taiwan and evaluated whether they had a higher risk of dementia than did the general population.A nationwide population-based cohort study was conducted among patients with CO poisoning identified using Taiwan's National Health Insurance Research Database (NHIRD) during 2004 to 2013. CO poisoning was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. The study cohort comprised patients with CO poisoning between 2005 and 2010 (N = 14,590). Each patient was age-, sex , and index date-matched with 4 randomly selected controls from the comparison cohort (N = 58,360). All patients were followed from the study date until dementia development, death, or the end of 2013. Cox proportional hazards regressions were performed for comparing the hazard ratios for dementia between the 2 cohorts.Incident cases of dementia were identified from the NHIRD.After adjustment for potential confounders, the study cohort was independently associated with a higher dementia risk (adjusted hazard ratio, 2.75; 95% confidence interval, 2.26-3.35).This population-based cohort study indicated that patients with CO poisoning have a higher risk of dementia than do people without CO poisoning. PMID- 26817905 TI - IgG4-related Kidney Disease Mimicking Malignant Ureter Tumor: Case Report and Literature Review. AB - Immunoglobulin G4-related disease is a recently recognized systemic disease that can affect any organ or tissue in the body, including the kidneys. IgG4-related kidney disease (IgG4-RKD) is an important part of immunoglobulin G4-related disease. The most common renal manifestation of IgG4-RKD is tubulointerstitial nephritis and glomerular lesions. There, however, is few case of IgG4-RKD mimicking malignant ureter tumor leading to severe hydronephrosis. We herein report an unusual case of IgG4-RKD mimicking malignancy.A 66-year-old Asian man presented to the nephrologist with soreness of loins, anorexia, and acute kidney injury in 2010. His renal function spontaneously improved after 2 weeks' hemodialysis without systemic steroid therapy. Four years later, he presented to the urologist with severe left hydronephrosis because of marked thickness of the left ureter wall. As a ureteral malignancy could not be ruled out, laparoscopic nephroureterectomy was performed.IgG4-related kidney disease was confirmed by the histologic examination. Then, repeat laboratory test showed almost complete recovery of renal function after initiation of steroidal therapy.This case highlights the rare possibility of IgG4-RKD mimicking malignant ureter tumor. Nephrologist and pathologists should be aware of the possibility that hydronephrosis with ureter obstruction may be involved in IgG4-RKD. PMID- 26817906 TI - Prevalence of Human Papillomavirus Genotypes Among Women With High-Grade Cervical Lesions in Beijing, China. AB - The aim of the study is to investigate the prevalence of high-risk human papillomavirus (hr-HPV) genotypes among Han women with high-grade cervical lesions in Beijing, China.Cervical cell specimens from patients with histopathologically confirmed cervical lesions at 7 hospitals in Beijing were examined with a validated HPV kit for 13 hr-HPV genotypes during the study period. The patients were divided into a low-grade cervical lesions group (cervical intraepithelial neoplasia grade 1, CIN1) and a high-grade cervical lesions group (CIN2+, including cervical intraepithelial neoplasia grade 2, CIN2; cervical intraepithelial neoplasia grade 3, CIN3; squamous cervical cancer, SCC; and adenocarcinoma of the cervix, ACC) based on the histopathology results.A total of 2817 eligible patients were enrolled, including 610 cases identified as CIN1 and 2207 as CIN2+. The hr-HPV positive rates in the CIN1 and CIN2+ groups were 78.2% (477/610) and 93.3% (2060/2207), respectively. The most frequently detected genotypes were HPV16, 58, 52 and18 in the CIN1 group and HPV16, 58, 33, and 52 in the CIN2+ group, in descending order of prevalence. In addition, the prevalence of HPV18 among the patients with ACC was 28.6% (14/49), significantly >7.2% (54/752) prevalence among the SCC patients (P < 0.001). Additionally, significantly more women in the CIN2+ group had multiple infections compared with those in the CIN1 group (38.1% and 24.9%, respectively; P < 0.001). However, as the cervical lesion grade increased, the prevalence of multiple hr-HPV infections gradually deceased to 44.2% in the CIN2 patients, 36.7% in the CIN3 patients, and 35.3% in the cervical cancer (CC) patients, which included SCC and ACC patients. In cases of multiple hr-HPV infections in the CIN2+ group, double infections accounted for ~76.6%, and HPV16+58, HPV16+52, and HPV16+18 were the most common combinations, in descending order. The most frequent combination for triple infections was HPV16+58+31, with a rate of 4.2%. The highest positive rate occurred in the <=24 year-old group for all types of cervical lesions.The prevalence of HPV genotypes in the targeted population with high-grade cervical lesions differs from that of other countries. This information could be helpful for the prevention of CC in Beijing, China. PMID- 26817907 TI - A Risk Model for Predicting Central Lymph Node Metastasis of Papillary Thyroid Microcarcinoma Including Conventional Ultrasound and Acoustic Radiation Force Impulse Elastography. AB - The aim of this prospective study was to propose a new rating system using a risk model including conventional ultrasound (US) and acoustic radiation force impulse (ARFI) elastography for predicting central lymph node metastasis (LNM) in patients with papillary thyroid microcarcinoma (PTMC).A total of 252 patients with PTMCs were enrolled, who were preoperatively evaluated by US and ARFI elastography including virtual touch tissue imaging (VTI) and virtual touch tissue quantification (VTQ). Risk factors of independent variables for central LNM were analyzed by univariate and multivariate analyses. A multivariate analysis was performed to create a predicting model and rating system.Of the 252 patients, 72 (28.6%) had central LNMs. Multivariate analysis revealed that rare internal flow (odds ratio [OR]: 4.454), multiple suspicious foci on US (OR: 5.136), capsule involvement (OR: 20.632), and VTI area ratio (VAR) > 1 (OR: 5.621) were independent risk factors for central LNM. The final predicting model was obtained and the risk score (RS) was defined as 1.5 * (if rare internal flow) + 1.6 * (if multiple suspicious foci on US) + 1.7 * (if VAR > 1) + 3.0 * (if capsule involvement). The rating system was divided into 5 stages. Stage I, <1.5; Stage II, 1.5 to 3.0; Stage III, 3.1 to 4.7; Stage IV, 4.8 to 6.3; and Stage V, 6.4 to 7.8. The risk rates of central LNM were 3.4% (2/59) in Stage I, 13.3% (13/98) in Stage II, 54.2% (39/72) in Stage III, 72.2% (13/18) in Stage IV, and 100% (5/5) in Stage V (P < 0.001).The results indicated that rare internal flow, multiple suspicious foci, capsule involvement on US, and VAR > 1 on ARFI elastography are the risk factors for predicting central LNM. The risk model developed in the study clearly predicts the risk of central LNM in patients with PTMC and thus has a potential to avoid unnecessary central compartment node dissection. PMID- 26817908 TI - Associations Between Target Lesion Restenosis and Drug-Eluting Balloon Use: An Observational Study. AB - Percutaneous coronary interventions (PCIs) with drug-eluting balloons (DEBs) have emerged as an adjunctive treatment for in-stent restenosis (ISR) lesions. However, recurrent restenosis still occurs following DEB use. Our study aimed to identify the associations of target lesion restenosis following DEB use over a 1 year clinical follow-up.Between November 2011 and May 2014, 246 patients were diagnosed with coronary artery ISR in our hospital. A total of 335 coronary ISR lesions were treated with DEBs. The 1-year patent coronary artery group was defined as those with negative noninvasive examinations and no clinical symptoms, or those with no angiographic restenosis. The 1-year current restenosis group was defined as those with angiographic restenosis. Clinical results were compared between 2 groups. Univariate and multivariate cox regression analyses were performed to identify the associations of target lesion restenosis following DEB use.Patients' average age was 64.96 +/- 10.68 years, and 77.2% were men. Non-ST segment elevation myocardial infarction was more frequent as the clinical presentation in the 1-year current restenosis group, whereas stable angina was more frequent in the 1-year patent coronary artery group. The 1-year current restenosis group exhibited higher percentages of comorbidities, including hypertension, diabetes, prior myocardial infarction, heart failure, prior coronary artery bypass grafting, and end-stage renal disease (ESRD). Regardless of ostial ISR or nonostial ISR, the results of drug-eluting stent ISR were worse than those for bare-metal stent ISR. Multivariate analysis revealed that ESRD, and coronary ostial lesion, and the severity of pre-PCI stenosis were independently associated with target lesion restenosis following DEB use (P = 0.020, P = 0.009, P = 0.026, respectively).ESRD, and coronary ostial lesion, and the severity of pre-PCI stenosis were independently associated with recurrent target lesion restenosis following DEB use. PMID- 26817909 TI - Infiltrating Lipoma of the Right Ventricle Involving the Interventricular Septum and Tricuspid Valve: Report of a Rare Case and Literature Review. AB - Cardiac lipoma, which are primary cardiac tumors, are rare entities often detected incidentally during imaging. There have been very few reports on the right ventricle (RV) lipoma. Here, we present a case of RV infiltrating lipoma involving the interventricular septum (IVS) and the tricuspid valve. Clinical symptoms, diagnostic procedures, multimodality imaging characteristics, and treatment are discussed, and the complete clinical data of this case and relevant details of retrospective literature are reviewed. The study described the case of a 48-year-old woman who suffered from occasional palpitation after exertion for 10 years. Imaging examinations, including echocardiography and cardiovascular magnetic resonance imaging (MRI), revealed a large mass adherent to the IVS and the right ventricular wall that was consistent with lipoma. The patient underwent surgical repair of the tricuspid valve and excision of the partial mass. The gross specimen revealed piles of 5 * 4 * 3 cm fragments with yellowish appearance and pathological results showed infiltrating lipoma.Lipoma is often asymptomatic and diagnosed incidentally. Surgical excision is the main therapeutic intervention, which is always performed in cases of symptomatic lipoma or when malignancy is suspected. Multimodality imaging would be great help in the diagnosis of cardiac lipoma. Echocardiography is a convenient method for follow up. PMID- 26817910 TI - Level of Pregnancy-associated Plasma Protein-A Correlates With Coronary Thin-cap Fibroatheroma Burden in Patients With Coronary Artery Disease: Novel Findings From 3-Vessel Virtual Histology Intravascular Ultrasound Assessment. AB - Pregnancy-associated plasma protein-A (PAPP-A) level is an independent predictor of acute cardiovascular event occurrence. To test the hypothesis that increased PAPP-A levels would be associated with a higher burden of coronary thin-cap fibroatheroma (TCFA) thereby underlying the heightened risk for cardiovascular events in patients with coronary artery disease; 154 patients (462 vessels and 975 plaques) with stable angina or non-ST-segment elevation acute coronary syndrome (NSTE-ACS) referred for percutaneous coronary intervention were assessed using 3-vessel virtual histology (VH)-intravascular ultrasound (IVUS). Thin-cap fibroatheroma virtual histology was defined as focal, necrotic core (NC)-rich (>=10% of cross-sectional area) plaques in contact with the lumen, and plaque burden >=40%. Pregnancy-associated plasma protein-A levels were determined by sandwich enzyme-linked immunosorbent assay, and patients were divided into 3 groups based on PAPP-A level tertiles. Although the highest PAPP-A level tertile was not associated with 3-vessel plaque number, it was associated with 3-vessel VH-TCFA number and necrotic core volume. Patients with >=3 VH-TCFAs had a higher PAPP-A level than patients with 1 to 3 VH-TCFAs or without any VH-TCFA (13.3 +/- 11.8 versus 7.8 +/- 4.7 versus 7.4 +/- 4.7 mIU/L, P < 0.001, respectively). Moreover, PAPP-A level was an independent predictor of higher total number of VH TCFAs (OR 1.18; 95% CI 1.07-1.29, P = 0.001). This VH-IVUS study demonstrated, for the first time to our knowledge, that higher PAPP-A levels are associated with higher 3-vessel TCFA burden in patients with coronary artery disease. Pregnancy-associated plasma protein-A, therefore, might be a useful serum biomarker to predict increased coronary TCFA burden and plaque instability. PMID- 26817911 TI - Antineutrophil Cytoplasmic Antibodies Associated With Infective Endocarditis. AB - To determine the prevalence of antineutrophil cytoplasmic antibodies (ANCA) in patients with infective endocarditis (IE) in internal medicine; and to compare clinical and biochemical features and outcome between patients exhibiting IE with and without ANCA.Fifty consecutive patients with IE underwent ANCA testing. The medical records of these patients were reviewed.Of the 50 patients with IE, 12 exhibited ANCA (24%). ANCA-positive patients with IE exhibited: longer duration between the onset of first symptoms and IE diagnosis (P = 0.02); and more frequently: weight loss (P = 0.017) and renal impairment (P = 0.08), lower levels of C-reactive protein (P = 0.0009) and serum albumin (P = 0.0032), involvement of both aortic and mitral valves (P = 0.009), and longer hospital stay (P = 0.016). Under multivariate analysis, significant factors for ANCA-associated IE were: longer hospital stay (P = 0.004), lower level of serum albumin (P = 0.02), and multiple valve involvement (P = 0.04). Mortality rate was 25% in ANCA patients; death was because of IE complications in all these patients.Our study identifies a high prevalence of ANCA in unselected patients with IE in internal medicine (24%). Our findings further underscore that ANCA may be associated with a subacute form of IE leading to multiple valve involvement and more frequent renal impairment. Because death was due to IE complications in all patients, our data suggest that aggressive therapy may be required to improve such patients' outcome. PMID- 26817912 TI - A Phase II Study of Sequential Capecitabine Plus Oxaliplatin Followed by Docetaxel Plus Capecitabine in Patients With Unresectable Gastric Adenocarcinoma: The TCOG 3211 Clinical Trial. AB - Fluorouracil and platinum are considered the standard treatment options for advanced gastric cancer. Docetaxel is also an effective agent and it shows no cross-resistance with fluorouracil and platinum. The combination treatment of docetaxel with fluorouracil and platinum has been explored, but it demonstrated intolerable toxicities. An alternative approach in the first-line treatment of gastric adenocarcinoma may be to use these agents sequentially. We aimed to evaluate the activity and safety profile of sequential chemotherapy with capecitabine plus oxaliplatin, followed by docetaxel plus capecitabine in the first-line treatment of unresectable gastric cancer.We conducted a phase II study of sequential first-line chemotherapy in advanced gastric cancer. Treatment consisted of 6 cycles of capecitabine plus oxaliplatin (capecitabine 1000 mg/m bid on days 1-10 and oxaliplatin 85 mg/m on day 1, every 2 weeks), followed by 4 cycles of docetaxel plus capecitabine (docetaxel 30 mg/m on days 1 and 8, capecitabine 825 mg/m bid on days 1-14, every 3 weeks). The primary end-point was the objective response rate.Fifty-one patients were enrolled: median age, 63 years; male/female: 37/14. The main grade 3 to 4 toxicities were a decreased absolute neutrophil count (25.4%), diarrhea (9.8%), and hand-foot syndrome (15.7%). The objective response rate was 61.7%. The median progression-free survival and overall survival were 8.6 and 11.0 months, respectively. Six patients (11.8%) received surgery after chemotherapy and 5 are still disease free.This sequential treatment demonstrated feasibility with a favorable safety profile and produced encouraging results in terms of activity and efficacy. PMID- 26817913 TI - The Associations Between the Religious Background, Social Supports, and Do-Not Resuscitate Orders in Taiwan: An Observational Study. AB - Prior studies have demonstrated important implications related to religiosity and a do-not-resuscitate (DNR) decision. However, the association between patients' religious background and DNR decisions is vague. In particular, the association between the religious background of Buddhism/Daoism and DNR decisions has never been examined. The objective of this study was to examine the association between patients' religious background and their DNR decisions, with a particular focus on Buddhism/Daoism.The medical records of the patients who were admitted to the 3 surgical intensive care units (SICU) in a university-affiliated medical center located at Northern Taiwan from June 1, 2011 to December 31, 2013 were retrospectively collected. We compared the clinical/demographic variables of DNR patients with those of non-DNR patients using the Student t test or chi test depending on the scale of the variables. We used multivariate logistic regression analysis to examine the association between the religious backgrounds and DNR decisions.A sample of 1909 patients was collected: 122 patients had a DNR order; and 1787 patients did not have a DNR order. Old age (P = 0.02), unemployment (P = 0.02), admission diagnosis of "nonoperative, cardiac failure/insufficiency" (P = 0.03), and severe acute illness at SICU admission (P < 0.01) were significantly associated with signing of DNR orders. Patients' religious background of Buddhism/Daoism (P = 0.04), married marital status (P = 0.02), and admission diagnosis of "postoperative, major surgery" (P = 0.02) were less likely to have a DNR order written during their SICU stay. Furthermore, patients with poor social support, as indicated by marital and working status, were more likely to consent to a DNR order during SICU stay.This study showed that the religious background of Buddhism/Daoism was significantly associated with a lower likelihood of consenting to a DNR, and poor social support was significantly associated with a higher likelihood of having a DNR order written during SICU stay. PMID- 26817914 TI - Combination of Intravesical Chemotherapy and Bacillus Calmette-Guerin Versus Bacillus Calmette-Guerin Monotherapy in Intermediate- and High-risk Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-analysis. AB - Urothelial carcinoma of the bladder has become a major cause of morbidity, mortality, and health-related costs. There is still no standard instillation therapy against bladder cancer. A meta-analysis was conducted to evaluate the efficacy and toxicity of adding chemotherapy to Bacillus Calmette-Guerin (BCG) in intermediate- and high-risk nonmuscle invasive bladder cancer (NMIBC).All randomized controlled trials (RCTs) that evaluated the efficacy of combination therapy and BCG monotherapy for intermediate- and high-risk NMIBC were comprehensively searched. Relevant databases, including PubMed, Embase, Cochrane Central Register of Controlled trials databases, and American Society of Clinical Oncology (http://www.asco.org/ASCO), the clinical trial registration website (ClinicalTrials.gov), and relevant trials from the references of selected studies were searched from initial state up to June 6, 2015. Random-effects model was used to estimate hazard ratios (HRs) statistics. All statistical analyses were performed by STATA (version 13.0, College Station, TX).Seven studies, including 1373 patients with intermediate- and high-risk NMIBC, were identified. For disease-free survival, the pooled HRs from all studies was 0.69 (95% confidence interval [CI], 0.48-1.00; P = 0.048). The disease-free survival benefit was more apparent among patients with intermediate-risk NMIBC (P = 0.002) or Ta/T1 with/without carcinoma in situ (P < 0.01). In subgroup analysis, a significant reduction in recurrence was found in studies that explored the influence of a perioperative single dose instillation compared with delayed BCG monotherapy (HR = 0.60; 95% CI, 0.38-0.92; P = 0.021). No significant difference was found for progression-free survival (HR = 0.78; 95% CI, 0.43-1.44; P = 0.435).Patients with intermediate- and high-risk NMIBC who underwent combination therapy achieved lower rates of recurrence than those who underwent BCG therapy alone. No difference in progression-free survival was found between the 2 different therapy schedules. Better efficacy for a perioperative single dose instillation compared with delayed BCG monotherapy was found in this meta-analysis. PMID- 26817915 TI - Nonalcoholic Fatty Liver Disease for Identification of Preclinical Carotid Atherosclerosis. AB - Nonalcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease, yet whether identification of NAFLD in asymptomatic individuals is helpful over established risk factors remains unknown. A total of 37,799 asymptomatic adults aged 20 years or older who underwent comprehensive health check-up examination, including abdominal and carotid artery duplex ultrasonography (US) were included in the analysis. Nonalcoholic fatty liver disease was diagnosed with US and exclusion of secondary causes of fat accumulation or other causes of chronic liver disease, and graded as mild or moderate to severe fatty liver. Individuals with carotid plaque identified on carotid artery US were considered at risk for cardiovascular disease. Metabolic syndrome (MetS) was defined by the adult treatment panel III criteria. Nonalcoholic fatty liver disease was an independent factor associated with carotid plaque in a dose-dependent manner (odds ratio [OR]; 95% confidence interval [CI]: 1.09 [1.03-1.16] and 1.13 [1.06-1.21] for mild and >= moderate degree of NAFLD). Among clinically-relevant subgroups, NAFLD was more closely associated with carotid plaque in young adults (aged < 60 years) without MetS (OR [95% CI]: 1.13 [1.03-1.19] and 1.16 [1.06-1.27] for mild and >= moderate degree of NAFLD) than old adults (aged >= 60 years) or with MetS (OR [95% CI]: 1.06 [0.97-1.17] and 1.07 [0.97-1.19] for mild and >= moderate degree NAFLD). In young adults without MetS, the prevalence of carotid plaques was 32.8% and the sensitivity and specificity of NAFLD for carotid plaque was 0.38 and 0.67, respectively. In conclusion, NAFLD is associated with carotid plaque independent of traditional risk factors, especially in young adults without MetS. Nonalcoholic fatty liver disease could help identify additional individuals with preclinical atherosclerosis in asymptomatic young adults without MetS, yet, showed suboptimal performance as a screening tool. PMID- 26817917 TI - Atopic Dermatitis and Association of Risk for Henoch-Schonlein Purpura (IgA Vasculitis) and Renal Involvement Among Children: Results From a Population-Based Cohort Study in Taiwan. AB - Elevation of Th2 cytokine-driven inflammatory mediators has been reported in acute stage of Henoch-Schonlein purpura (HSP). However, the temporal interaction between Th2-mediated allergic diseases and HSP with renal involvement remains unknown. Herein, we conducted a population-based cohort analysis to investigate the risk of HSP and renal involvement in children with atopic dermatitis (AD) as 1 of the first steps in the atopic march.From 2000 to 2007, 95,208 children with newly diagnosed AD and 190,416 randomly selected non-AD controls were included in the study. By the end of 2008, incidences of HSP in both cohorts and the AD cohort to non-AD cohort hazard ratios (HRs) and confidence intervals (CIs) were measured. Comparison of renal involvement in HSP between children with and without AD was analyzed.The incidence of HSP during the study period was 1.75 fold greater (95% CI: 1.27-2.42) in the AD cohort than in the non-AD cohort (14.2 vs 8.11 per 100,000 person-years). The AD to non-AD HR of HSP was greater for girls (1.92, 95% CI: 1.18-3.13), children older than 6 years (2.54, 95% CI: 1.15 5.59), and those living in less urbanized area (2.74, 95% CI: 1.10-6.82). Concurrent allergic rhinitis or asthma did not increase the HR of HSP further. The HR for HSP in AD children increased from 0.67 (95% CI: 0.41-1.11) for those with <=2 AD-related visits to 9.77 (95% CI: 6.44-14.8) for those with >4 visits (P < 0.0001, by the trend test). The risk of developing HSP in the AD cohort was highest within first year after AD diagnosis (HR: 3.99; 95% CI: 1.61-9.89). AD cohort with HSP had higher occurrence rate of renal involvement, particular hematuria, than non-AD cohort with HSP.AD children had a greater risk of developing HSP and HSP with renal involvement. Further research is needed to clarify the role of allergy in the pathogenesis of HSP and renal involvement. PMID- 26817916 TI - Mismatch Repair Gene Expression as a Predictor of Tumor Responses in Patients With Rectal Cancer Treated With Preoperative Chemoradiation. AB - This study evaluated the predictive and prognostic value of expression of mismatch repair (MMR) protein, including MLH1, MSH2, and MSH6 in rectal cancer patients with preoperative chemoradiotherapy.MMR protein expression was measured by immunohistochemistry in both pretreatment biopsies (pre-) and pathologic specimens (post-) from 209 patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy and radical surgery. The patients were followed for a median period of 44 months.A pathologic complete response (pCR) was observed in 30 patients (14.4%). The expression levels of MLH1, MSH2, and MSH6 were not significantly different between the pCR and non-pCR groups. A multivariate analysis revealed that tumor differentiation, postoperative chemotherapy, and pre-MSH6 expression were independent predictors of overall survival; ypN category and perineural invasion were independent predictors of disease-free survival. The pre-MSH6 expression was significantly associated with tumor budding and expression of all MMR proteins. On multivariate analysis, ypN category and post-MSH6 expression were independent predictors for local recurrence.In our study, we observed the independent prognostic value of MSH6 expression in pretreatment tissue on overall survival and MSH6 expression after chemoradiation on local recurrence. Constitutive MSH6 expression before and after preoperative therapy may be a useful tool for prediction of oncologic outcome in locally advanced rectal cancer. PMID- 26817918 TI - Dynamic Changes of Pulmonary Arterial Pressure and Ductus Arteriosus in Human Newborns From Birth to 72 Hours of Age. AB - Normal pulmonary artery pressure and pulmonary hypertension assessment of newborns is rarely reported. The aim of the study is to explore dynamic changes of pulmonary arterial pressure and ductus arteriosus in human newborns from birth to 72 h of age with echocardiography.A total of 76 cases of normal newborns were prospectively detected by echocardiography after birth of 2 h, 6 h, 12 h, 24 h, 48 h, and 72 h, respectively. Ductus arteriosus diameter, blood shunt direction, blood flow velocity, and pressure gradient were recorded. The brachial artery blood pressure were measured to estimate the pulmonary artery systolic pressure (PASP) and pulmonary artery diastolic pressure (PADP) using patent ductus arteriosus pressure gradient method. The mean pulmonary artery pressure (PAMP) were calculated by equation of PAMP = PADP + 1/3(PASP-PADP).(1) There were 76 cases of normal newborns. Among them, 29 cases (38%) ductus arteriosus closed within 24 h, 59 cases (78%) closed within 48 h, 72 cases (95%) closed within 72 h, and 4 cases (5%) ductus arteriosus not closed within 72 h. (2) The ductus arteriosus diameter of 2 h, 6 h, 12 h, 24 h, 48 h, and 72 h after birth was 4.60 +/- 0.59 mm, 3.37 +/- 0.59 mm, 2.47 +/- 0.49 mm, 1.89 +/- 0.41 mm, 1.61 +/- 0.35 mm, and 1.20 +/- 0.24 mm, respectively. Compared all of the ductus arteriosus diameter of the above time periods, there were statistically differences with P < 0.05, respectively. (3) The mean PASP in 2 h, 6 h, 12 h, 24 h, 48 h, 72 h after birth were 76.58 +/- 7.28 mm Hg, 65.53 +/- 9.25mm Hg, 52.51 +/- 9.07 mm Hg, 43.83 +/- 7.90 mm Hg, 38.07 +/- 8.26 mm Hg, and 36 +/- 6.48 mm Hg, respectively. The PADP of the above time period were 37.88 +/- 5.56 mm Hg, 29.93 +/- 7.91 mm Hg, 23.43 +/- 7.37 mm Hg, 19.70 +/- 8.51 mm Hg, 13.85 +/- 5.58 mm Hg, 13.25 +/- 6.18 mm Hg, respectively. The PAMP of the above time period were 63.41 +/- 7.03 mm Hg, 51.78 +/- 9.82 mm Hg, 40.94 +/- 9.32 mm Hg, 34.39 +/- 9.89 mm Hg, 26.23 +/- 7.49 mm Hg, 25.25 +/- 8.29 mm Hg, respectively. There were statistically differences with P < 0.05 between each time periods of PASP, PADP, and PAMP. (4) The upper 95% limit reference range of PASP of normal newborns of 72 h after birth were 39.97 mm Hg.(1) Normal newborns ductus arteriosus diameter gradually decreased after birth, and 95% of them spontaneous closed within 24 to 72 h. (2) Normal newborns pulmonary artery pressure showed a gradually decline after birth, the upper 95% limit reference range for PASP measured in normal newborns <72 h of age was 39.97 mm Hg. Therefore, the diagnostic criteria of newborns pulmonary hypertension may be >40.00 mm Hg according to our limited study. PMID- 26817919 TI - Actinobacillus actinomycetemcomitans Keratitis After Glaucoma Infiltration Surgery: A Clinical Report and Literature Review. AB - Actinobacillus actinomycetemcomitans infection is a rare and easily misdiagnosed ocular disease. In this article, the authors report a chronic, purulent, and difficult-to-treat case of A actinomycetemcomitans keratitis following a glaucoma infiltration surgery.A 56-year-old man with a long-standing history of open-angle glaucoma in both eyes presented with a 12-week history of ocular pain, redness, and blurred vision in his right eye. He underwent a glaucoma infiltration surgery in his right eye 6 months ago. Three months postoperatively, he developed peripheral corneal stromal opacities associated with a white, thin, cystic bleb, and conjunctival injection. These opacities grew despite topical treatment with topical tobramycin, levofloxacin, natamycin, amikacin, and metronidazole eye drops.Multiple corneal scrapings revealed no organisms, and no organisms grew on aerobic, anaerobic, fungal, or mycobacterial cultures. The patient's right eye developed a severe purulent corneal ulcer with a dense hypopyon and required a corneal transplantation. Histopathologic analysis and 16S ribosomalribonucleic acid polymerase chain reaction sequencing revealed A actinomycetemcomitans as the causative organism. Postoperatively, treatment was initiated with topical levofloxacin and cyclosporine, as well as oral levofloxacin and cyclosporine. Graft and host corneal transparency were maintained at the checkup 1 month after surgery.Although it is a rare cause of corneal disease, A actinomycetemcomitans should be suspected in patients with keratitis refractory to topical antibiotic therapy. Delay in diagnosis and appropriate treatment can result in vision loss. PMID- 26817920 TI - Alzheimer disease is in part a thrombohemorrhagic disorder. PMID- 26817921 TI - Overcrowding-mediated stress alters cell proliferation in key neuroendocrine areas during larval development in Rhinella arenarum. AB - Exposure to adverse environmental conditions can elicit a stress response, which results in an increase in endogenous corticosterone levels. In early life stages, it has been thoroughly demonstrated that amphibian larval growth and development is altered as a consequence of chronic stress by interfering with the metamorphic process, however, the underlying mechanisms involved have only been partially disentangled. We examined the effect of intraspecific competition on corticosterone levels during larval development of the toad Rhinella arenarum and its ultimate effects on cell proliferation in particular brain areas as well as the pituitary gland. While overcrowding altered the number of proliferating cells in the pituitary gland, hypothalamus, and third ventricle of the brain, no differences were observed in areas which are less associated with neuroendocrine processes, such as the first ventricle of the brain. Apoptosis was increased in hypothalamic regions but not in the pituitary. With regards to pituitary cell populations, thyrotrophs but not somatoatrophs and corticotrophs showed a decrease in the cell number in overcrowded larvae. Our study shows that alterations in growth and development, produced by stress, results from an imbalance in the neuroendocrine systems implicated in orchestrating the timing of metamorphosis. PMID- 26817922 TI - Anisotropic Nanoparticles and Anisotropic Surface Chemistry. AB - Anisotropic nanoparticles are powerful building blocks for materials engineering. Unusual properties emerge with added anisotropy-often to an extraordinary degree enabling countless new applications. For bottom-up assembly, anisotropy is crucial for programmability; isotropic particles lack directional interactions and can self-assemble only by basic packing rules. Anisotropic particles have long fascinated scientists, and their properties and assembly behavior have been the subjects of many theoretical studies over the years. However, only recently has experiment caught up with theory. We have begun to witness tremendous diversity in the synthesis of nanoparticles with controlled anisotropy. In this Perspective, we highlight the synthetic achievements that have galvanized the field, presenting a comprehensive discussion of the mechanisms and products of both seed-mediated and alternative growth methods. We also address recent breakthroughs and challenges in regiospecific functionalization, which is the next frontier in exploiting nanoparticle anisotropy. PMID- 26817923 TI - Stable isotope analysis of diet confirms niche separation of two sympatric species of Namib Desert lizard. AB - We used stable isotopes of carbon and nitrogen to study the trophic niche of two species of insectivorous lizards, the Husab sand lizard Pedioplanis husabensis and Bradfield's Namib day gecko living sympatrically in the Namib Desert. We measured the delta(13) C and delta(15) N ratios in lizard blood tissues with different turnover times (whole blood, red blood cells and plasma) to investigate lizard diet in different seasons. We also measured the delta(13) C and delta(15) N ratios in available arthropod prey and plant tissues on the site, to identify the avenues of nutrient movement between lizards and their prey. Through the use of stable isotope mixing models, we found that the two lizard species relied on a largely non-overlapping but seasonally variable array of arthropods: P. husabensis primarily fed on termites, beetles and wasps, while R. bradfieldi fed mainly on ants, wasps and hemipterans. Nutrients originating from C3 plants were proportionally higher for R. bradfieldi than for P. husabensis during autumn and late autumn/early winter, although not summer. Contrary to the few available data estimating the trophic transfer of nutrients in ectotherms in mixed C3 and C4 /crassulacean acid metabolism (CAM) plant landscapes, we found that our lizard species primarily acquired nutrients that originated from C4 /CAM plants. This work adds an important dimension to the general lack of studies using stable isotope analyses to estimate lizard niche partitioning and resource use. PMID- 26817924 TI - Demographically Corrected Normative Standards for the Spanish Language Version of the NIH Toolbox Cognition Battery. AB - Hispanics are the fastest growing ethnicity in the United States, yet there are limited well-validated neuropsychological tools in Spanish, and an even greater paucity of normative standards representing this population. The Spanish NIH Toolbox Cognition Battery (NIHTB-CB) is a novel neurocognitive screener; however, the original norms were developed combining Spanish- and English-versions of the battery. We developed normative standards for the Spanish NIHTB-CB, fully adjusting for demographic variables and based entirely on a Spanish-speaking sample. A total of 408 Spanish-speaking neurologically healthy adults (ages 18-85 years) and 496 children (ages 3-7 years) completed the NIH Toolbox norming project. We developed three types of scores: uncorrected based on the entire Spanish-speaking cohort, age-corrected, and fully demographically corrected (age, education, sex) scores for each of the seven NIHTB-CB tests and three composites (Fluid, Crystallized, Total Composites). Corrected scores were developed using polynomial regression models. Demographic factors demonstrated medium-to-large effects on uncorrected NIHTB-CB scores in a pattern that differed from that observed on the English NIHTB-CB. For example, in Spanish-speaking adults, education was more strongly associated with Fluid scores, but showed the strongest association with Crystallized scores among English-speaking adults. Demographic factors were no longer associated with fully corrected scores. The original norms were not successful in eliminating demographic effects, overestimating children's performances, and underestimating adults' performances on the Spanish NIHTB-CB. The disparate pattern of demographic associations on the Spanish versus English NIHTB-CB supports the need for distinct normative standards developed separately for each population. Fully adjusted scores presented here will aid in more accurately characterizing acquired brain dysfunction among U.S. Spanish-speakers. PMID- 26817925 TI - Determination of trace elements and their concentrations in clay balls: problem of geophagia practice in Ghana. AB - Ten samples of 100 g weight were subsampled from 1400 g of the clay balls from which the contained trace element levels were determined by X-ray fluorescence technique. The results of trace elements in the clay balls were calibrated using certified reference materials "MAJMON" and "BH-1." The results showed elevated concentrations but with different concentration levels in the regions, particularly with arsenic, chromium, cobalt, Cs, Zr and La. These trace elements contained in the clay balls are known to be hazardous to human health. Thence the relatively high concentrations of these listed trace elements in clay balls in the three regions, namely Ashanti, Upper East and Volta, which are widely sold in markets in Ghana, could present negative health impact on consumers if consumed at 70 g per day or more and on regular basis. On the basis of these, the study concludes an investigation to establish breakeven range for trace element concentrations in the clay balls as it has been able to demonstrate the uneven and elevated values in them. The standardized safe ranges of trace elements will make the practice safer for the people that ingest clay balls in Ghana. PMID- 26817926 TI - Health risk assessment of groundwater arsenic pollution in southern Taiwan. AB - Residents of the Pingtung Plain, Taiwan, use groundwater for drinking. However, monitoring results showed that a considerable portion of groundwater has an As concentration higher than the safe drinking water regulation of 10 MUg/L. Considering residents of the Pingtung Plain continue to use groundwater for drinking, this study attempted to evaluate the exposure and health risk from drinking groundwater. The health risk from drinking groundwater was evaluated based on the hazard quotient (HQ) and target risk (TR) established by the US Environmental Protection Agency. The results showed that the 95th percentile of HQ exceeded 1 and TR was above the safe value of threshold value of 10-6. To illustrate significant variability of the drinking water consumption rate and body weight of each individual, health risk assessments were also performed using a spectrum of daily water intake rate and body weight to reasonably and conservatively assess the exposure and health risk for the specific subgroups of population of the Pingtung Plain. The assessment results showed that 0.01-7.50 % of the population's HQ levels are higher than 1 and as much as 77.7-93.3 % of the population being in high cancer risk category and having a TR value >10-6. The TR estimation results implied that groundwater use for drinking purpose places people at risk of As exposure. The government must make great efforts to provide safe drinking water for residents of the Pingtung Plain. PMID- 26817927 TI - Are antibiotics a safe and effective treatment for acute uncomplicated appendicitis? AB - Acute appendicitis is a common cause of acute abdominal pain and the most frequent cause of emergency abdominal surgery. In the last two decades, growing evidence has been published about the use of antibiotics as the exclusive treatment for acute appendicitis. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified only one systematic review including one pertinent randomized trial. We generated a summary of findings following the GRADE approach. We concluded the use of antibiotics to treat acute uncomplicated appendicitis may be less effective than appendectomy and probably increases major complications compared with appendectomy. PMID- 26817928 TI - Low vascularity predicts favourable outcomes in leiomyoma patients treated with uterine artery embolization. AB - OBJECTIVES: To investigate the clinical factors predicting outcomes of leiomyoma treated with uterine artery embolization (UAE). METHODS: A total of 183 uterine leiomyoma patients undergoing UAE were retrospectively analyzed. Patient age, characteristics of vascular supply in magnetic resonance imaging (MRI)/digital subtraction angiography (DSA), number, size and location of leiomyoma were recorded. Leiomyoma regrowth, new leiomyoma appearance and recurrence of any previously reported symptoms were carefully monitored over a mean follow-up of 30 months (median 32 months, range 12-80). Potential recurrence risk factors were analyzed by univariate and multivariate cox regression analysis. RESULTS: Twenty three recurrences were recorded. The difference in the vascularity classification systems between MRI and DSA was not statistically significant (P = 0.059). High vascularity in MRI, high vascularity in DSA and multiple leiomyoma showed a significant risk of recurrence using univariate and multivariate analysis (P = 0.004, P < 0.001 and P = 0.023, respectively). The other factors were not significantly associated with leiomyoma recurrence (P > 0.05). CONCLUSION: Low vascularity and solitary leiomyoma indicated favourable outcomes in patients treated with UAE. KEY POINTS: * Low vascularity and solitary mass predicted favourable outcomes in UAE-treated patients. * MRI might provide information on vascularity in leiomyoma before UAE. * Variations in vascular supply, age, size, location were not associated with recurrence. PMID- 26817930 TI - [Self injury in adolescence]. AB - Self-injury often occurs for the first time in adolescence. The current classification distinguishes several groups: (1) factitious disorder imposed on self and factitious disorder imposed on another, (2) nonsuicidal self-injury (NSSI) and (3) obsessive-compulsive (OCD) and related disorders. The differential diagnosis includes a wide spectrum of psychiatric diseases, including borderline personality disorder (BPD), inherited disorders like Lesch-Nyhan syndrome (LNS) and also body modifications. In all these cases, self-harm is a subphenomenon. This review focuses on typical dermatological pictures. PMID- 26817929 TI - Randomized controlled trial of relaxation music to reduce heart rate in patients undergoing cardiac CT. AB - OBJECTIVES: To evaluate the heart rate lowering effect of relaxation music in patients undergoing coronary CT angiography (CCTA), pulmonary vein CT (PVCT) and coronary calcium score CT (CCS). METHODS: Patients were randomised to a control group (i.e. standard of care protocol) or to a relaxation music group (ie. standard of care protocol with music). The groups were compared for heart rate, radiation dose, image quality and dose of IV metoprolol. Both groups completed State-Trait Anxiety Inventory anxiety questionnaires to assess patient experience. RESULTS: One hundred and ninety-seven patients were recruited (61.9 % males); mean age 56y (19-86 y); 127 CCTA, 17 PVCT, 53 CCS. No significant difference in heart rate, radiation dose, image quality, metoprolol dose and anxiety scores. 86 % of patients enjoyed the music. 90 % of patients in the music group expressed a strong preference to have music for future examinations. The patient cohort demonstrated low anxiety levels prior to CT. CONCLUSION: Relaxation music in CCTA, PVCT and CCS does not reduce heart rate or IV metoprolol use. Patients showed low levels of anxiety indicating that anxiolytics may not have a significant role in lowering heart rate. Music can be used in cardiac CT to improve patient experience. KEY POINTS: * Relaxation music does not reduce heart rate in cardiac CT * Relaxation music does not reduce beta-blocker use in cardiac CT * Relaxation music has no effect on cardiac CT image quality * Low levels of anxiety are present in patients prior to cardiac CT * Patients enjoyed the relaxation music and this results in improved patient experience. PMID- 26817931 TI - Television: a way of distracting patients during sexual and reproductive healthcare procedures. PMID- 26817932 TI - Advanced glycation end products are elevated in cystic fibrosis-related diabetes and correlate with worse lung function. AB - BACKGROUND: The onset of cystic fibrosis-related diabetes (CFRD) exacerbates lung function decline and increases mortality. One pathway that may worsen the lung dysfunction associated with CFRD is that of the receptor for advanced glycation end products (RAGE) and its ligands. METHODS: Human plasma was obtained from age matched healthy, CF and CFRD patients. Plasma RAGE ligands (i.e. advanced glycation end products, S100A12, and high-mobility group protein B1) and soluble RAGE (sRAGE) levels were measured. RESULTS: CFRD patients had elevated plasma levels of AGEs and S100A12. Soluble RAGE, a RAGE ligand decoy receptor, was not significantly different between groups. Plasma AGE levels and S100A12 levels had significantly negative correlations with FEV1. CONCLUSIONS: AGEs are significantly elevated in CFRD and correlate negatively with FEV1. CFRD patients did not have significant increases in the decoy sRAGE, suggesting there may be heightened binding and activation of RAGE in CFRD exacerbating activation of proinflammatory pathways. PMID- 26817933 TI - Timing of Puberty in Overweight Versus Obese Boys. AB - BACKGROUND AND OBJECTIVE: Studies of the relationship of weight status with timing of puberty in boys have been mixed. This study examined whether overweight and obesity are associated with differences in the timing of puberty in US boys. METHODS: We reanalyzed recent community-based pubertal data from the American Academy of Pediatrics' Pediatric Research in Office Settings study in which trained clinicians assessed boys 6 to 16 years for height, weight, Tanner stages, testicular volume (TV), and other pubertal variables. We classified children based on BMI as normal weight, overweight, or obese and compared median age at a given Tanner stage or greater by weight class using probit and ordinal probit models and a Bayesian approach. RESULTS: Half of boys (49.9%, n = 1931) were white, 25.8% (n = 1000) were African American, and 24.3% (n = 941) were Hispanic. For genital development in white and African American boys across a variety of Tanner stages, we found earlier puberty in overweight compared with normal weight boys, and later puberty in obese compared with overweight, but no significant differences for Hispanics. For TV (>=3 mL or >=4 mL), our findings support earlier puberty for overweight compared with normal weight white boys. CONCLUSIONS: In a large, racially diverse, community-based sample of US boys, we found evidence of earlier puberty for overweight compared with normal or obese, and later puberty for obese boys compared with normal and overweight boys. Additional studies are needed to understand the possible relationships among race/ethnicity, gender, BMI, and the timing of pubertal development. PMID- 26817935 TI - Physical Examination Findings Among Children and Adolescents With Obesity: An Evidence-Based Review. AB - Overweight and obesity affects 1 in 3 US children and adolescents. Clinical recommendations have largely focused on screening guidelines and counseling strategies. However, the physical examination of the child or adolescent with obesity can provide the clinician with additional information to guide management decisions. This expert-based review focuses on physical examination findings specific to children and adolescents with obesity. For each physical examination element, the authors define the finding and its prevalence among pediatric patients with obesity, discuss the importance and relevance of the finding, describe known techniques to assess severity, and review evidence regarding the need for additional evaluation. The recommendations presented represent a comprehensive review of current evidence as well as expert opinion. The goal of this review is to highlight the importance of conducting a targeted physical examination during pediatric weight management visits. PMID- 26817934 TI - Promotion of Positive Parenting and Prevention of Socioemotional Disparities. AB - OBJECTIVE: The goal of this study was to determine what effects pediatric primary care interventions, focused on promotion of positive parenting through reading aloud and play, have on the socioemotional development of toddlers from low income, primarily immigrant households. METHODS: This randomized controlled trial included random assignment to 1 of 2 interventions (Video Interaction Project [VIP] or Building Blocks [BB]) or to a control group. Mother-newborn dyads were enrolled postpartum in an urban public hospital. In VIP, dyads met with an interventionist on days of well-child visits; the interventionist facilitated interactions in play and shared reading through provision of learning materials and review of videotaped parent-child interactions. In BB, parents were mailed parenting pamphlets and learning materials. This article analyzes socioemotional outcomes from 14 to 36 months for children in VIP and BB versus control. RESULTS: A total of 463 dyads (69%) contributed data. Children in VIP scored higher than control on imitation/play and attention, and lower on separation distress, hyperactivity, and externalizing problems, with effect sizes ~0.25 SD for the sample as a whole and ~0.50 SD for families with additional psychosocial risks . Children in BB made greater gains in imitation/play compared with control. CONCLUSIONS: These findings support the efficacy of VIP, a preventive intervention targeting parent-child interactions, for enhancing socioemotional outcomes in low-income toddlers. Given the low cost and potential for scalability of primary care interventions, findings support expansion of pediatric-based parenting programs such as VIP for the primary prevention of socioemotional problems before school entry. PMID- 26817936 TI - Microcirculatory effects of zinc on fructose-fed hamsters. AB - BACKGROUND AND AIMS: Fructose is a major dietary component directly related to vascular dysfunction and diseases such as obesity, diabetes, and hypertension. Zinc is considered a non-pharmacological alternative for treating diabetes due to its antioxidant and hyperglycemia-lowering effects in diabetic animals. Therefore, the aim of this study was to evaluate the effects of dietary zinc supplementation on the microcirculatory parameters of fructose-fed hamsters. METHODS AND RESULTS: Male hamsters (Mesocricetus auratus) were fed drinking water substituted by 10% fructose solution for 60 days, whereas control animals were fed drinking water alone. Their microcirculatory function was evaluated using cheek pouch preparation, as well as their blood glucose and serum insulin levels. Their microcirculatory responses to acetylcholine (ACh, an endothelium-dependent vasodilator) and to sodium nitroprusside (SNP, an endothelium-independent vasodilator) as well as the increase in macromolecular permeability induced by 30 min of ischemia/reperfusion (I/R) were noted. Endothelium-dependent vasodilation was significantly increased in control animals with high zinc supplementation compared to the groups without zinc supplementation. Zinc was able to protect against plasma leakage induced by I/R in all control and fructose-fed groups, although the microvascular permeability was higher in animals fed drinking water substituted by 10% fructose solution compared to those fed filtered drinking water alone. CONCLUSION: Our results indicate that dietary zinc supplementation can improve microvascular dysfunction by increasing endothelial-dependent dilatation and reducing the increase in macromolecular permeability induced by I/R in fructose-fed animals. PMID- 26817937 TI - Serum palmitoleate acts as a lipokine in subjects at high cardiometabolic risk. AB - BACKGROUND AND AIM: Clinical data on the role as a lipokine of de novo lipogenesis-derived palmitoleic acid (C16:1n-7cis) in serum non-esterified fatty acids (palmitoleate) are scarce. We aimed to assess whether palmitoleate relates to cardiometabolic risk. METHODS AND RESULTS: In this cross-sectional study we included 358 individuals aged 30-65-years at high cardiovascular risk. We tested the association of palmitoleate (determined by gas chromatography) with metabolic syndrome (MS) and its components (defined by ATPIII criteria), fatty liver index (a surrogate of non-alcoholic fatty liver disease [NAFLD]), and subclinical atherosclerosis (determined as ultrasound-measured carotid intima-media thickness and arterial stiffness). Palmitoleate concentration was higher in women compared with men (median +/- range interquartile, 1.36 +/- 0.96 vs. 0.97 +/- 0.77 MUmol/L respectively, P < 0.001). In both genders palmitoleate concentration was associated with a higher prevalence of MS: men, odds ratio [OR: 1.12 (95%CI: 1.03; 1.23, P = 0.010)]; women [OR: 1.07 (95%CI: 1.03; 1.13, P = 0.005)], and all of its components except low HDL-cholesterol and hypertriglyceridemia. Palmitoleate was also associated with increased risk of NAFLD in both men [OR: 1.12 (95%CI: 1.03; 1.29, P = 0.031)] and women [OR: 1.11 (95%CI: 1.05; 1.19, P = 0.001)]. No associations with subclinical atherosclerosis were detected. CONCLUSIONS: Our observational data supports a relationship between de novo lipogenesis-derived circulating palmitoleic acid (palmitoleate) and increased cardiometabolic risk. PMID- 26817939 TI - On the evolution of developmental mechanisms: Divergent polarities in leaf growth as a case study. AB - Most model plants used to study leaf growth share a common developmental mechanism, namely basipetal growth polarity, wherein the distal end differentiates first with progressively more proliferative cells toward the base. Therefore, this base-to-tip growth pattern has served as a paradigm to explain leaf growth and also formed the basis for several computational models. However, our recent report in The Plant Cell on the investigation of leaf growth in 75 eudicot species covering a wide range of eudicot families showed that leaves grow with divergent polarities in the proximo-distal axis or without any obvious polarity. This divergence in growth polarity is linked to the expression divergence of a conserved microRNA-transcription factor module. This study raises several questions on the evolutionary origin of leaf growth pattern, such as 'when and why in evolution did the divergent growth polarities arise?' and 'what were the molecular changes that led to this divergence?'. Here, we discuss a few of these questions in some detail. PMID- 26817938 TI - Abdominal fat radiodensity, quantity and cardiometabolic risk: The Multi-Ethnic Study of Atherosclerosis. AB - BACKGROUND AND AIMS: Fat radiodensity, as measured by fat attenuation on computed tomography (CT), has emerged as a potential biomarker of "fat quality." We sought to characterize the relationship between fat radiodensity and quantity in subcutaneous, visceral, and intermuscular fat depots, and its role in inflammation, insulin resistance, and metabolic syndrome (MetS). METHODS AND RESULTS: We studied 1511 individuals from the Multi-Ethnic Study of Atherosclerosis who underwent CT for measurement of regional fat distribution and radiodensity, along with biomarker assessments and adjudication of incident metabolic syndrome (MetS). Linear, logistic and Cox regression analyses were used to measure association between fat radiodensity and (1) fat quantity, (2) biomarkers of cardiometabolic dysfunction, and (3) both prevalent and incident MetS. In each fat depot, radiodensity was strongly and inversely associated with quantity (e.g., visceral fat radiodensity vs. quantity: rho = -0.82, P < 0.01). After adjustment for age, sex and race, lower visceral fat radiodensity was associated with greater C-reactive protein, leptin and insulin, but lower adiponectin (P < 0.01 for all). After full adjustment for cardiovascular disease risk factors, visceral (but not subcutaneous or intermuscular) fat radiodensity was associated with prevalent MetS (OR = 0.96, 95% CI = 0.93-0.99, P = 0.01). Moreover, lower visceral fat radiodensity was associated with incident MetS after the same adjustment (HR = 0.95, 95% CI 0.93-0.98, P < 0.01). However, this association became non-significant after further adjustment for visceral fat quantity. CONCLUSION: Fat radiodensity is strongly correlated with fat quantity and relevant inflammatory biomarkers. Fat radiodensity (especially for visceral fat) may be a complementary, easily assessed marker of cardiometabolic risk. PMID- 26817940 TI - Near real-time vaccine safety surveillance using electronic health records-a systematic review of the application of statistical methods. AB - PURPOSE: Pre-licensure studies have limited ability to detect rare adverse events (AEs) to vaccines, requiring timely post-licensure studies. With the increasing availability of electronic health records (EHR) near real-time vaccine safety surveillance using these data has emerged as an option. We reviewed methods currently used to inform development of similar systems for countries considering their introduction. METHODS: Medline, EMBASE and Web of Science were searched, with additional searches of conference abstract books. Questionnaires were sent to organizations worldwide to ascertain unpublished studies. Eligible studies used EHR and regularly assessed pre-specified AE to vaccine(s). Key features of studies were compared descriptively. RESULTS: From 2779 studies, 31 were included from the USA (23), UK (6), and Taiwan and New Zealand (1 each). These were published/conducted between May 2005 and April 2015. Thirty-eight different vaccines were studied, focusing mainly on influenza (47.4%), especially 2009 H1N1 vaccines. Forty-six analytic approaches were used, reflecting frequency of EHR updates and the AE studied. Poisson-based maximized sequential probability ratio test was the most common (43.5%), followed by its binomial (23.9%) and conditional versions (10.9%). Thirty-seven of 49 analyses (75.5%) mentioned control for confounding, using an adjusted expected rate (51.4% of those adjusting), stratification (16.2%) or a combination of a self-controlled design and stratification (13.5%). Guillain-Barre syndrome (11.9%), meningitis/encephalitis/myelitis (11.9%) and seizures (10.8%) were studied most often. CONCLUSIONS: Near real-time vaccine safety surveillance using EHR has developed over the past decade but is not yet widely used. As more countries have access to EHR, it will be important that appropriate methods are selected, considering the data available and AE of interest. PMID- 26817941 TI - Diagnosis and phylogenetic analysis of orf virus in Aleppo and Saanen goats from an outbreak in Turkey. PMID- 26817942 TI - Apolipoprotein E epsilon 2 allele and low serum cholesterol as risk factors for gastric cancer in a Chinese Han population. AB - Apolipoprotein E (apoE) mediates lipid metabolism both in peripheral and in the brain. The human APOE gene has three polymorphic alleles that influence the risk for various types of cancer and neurodegenerative diseases. A potential association between APOE allele and the risk for gastric cancer has been implicated, but the specific allele involved and potential associations with the subtype and the grade of cancer malignancy need further clarification. We screened the APOE genotype in 550 gastric cancer patients and 550 non-cancer control individuals and found that the presence of the APOE epsilon2 and lower serum total cholesterol are associated with an increased risk for gastric cancer (all P <= 0.0005). Interestingly, APOE epsilon2 is also correlated with increased risk for both intestinal and diffuse histotypes but not with TN classification or stage in gastric cancer patients, suggesting that APOE polymorphic alleles are associated with the risk of development but unlikely the progression of gastric cancer. Since epsilon2 carriers have lower levels of serum total cholesterol than non-epsilon2 carriers, our findings suggest that the increased risk for gastric cancer by APOE epsilon2 allele might be mediated through lowered serum total cholesterol levels. PMID- 26817944 TI - One Health: competing perspectives in an emerging field. AB - Over the last decade, One Health has attracted considerable attention from researchers and policymakers. The concept argues that the fields of human, animal and environmental health ought to be more closely integrated. Amid a flurry of conferences, projects and publications, there has been substantial debate over what exactly One Health is and should be. This review summarizes the main trends in this emerging discussion, highlighting the fault lines between different perspectives on One Health. Some have shown that One Health's call to synthesize knowledge from different disciplines can lead to better interventions. Others, however, argue that One Health's challenge to existing practice must go further, and set out a vision that foregrounds the social and economic drivers of disease. Meanwhile, recent examples of One Health in practice highlight the potential but also the challenges of institutionalizing cooperation. We also discuss the promise and pitfalls of using complexity theory to tackle multifaceted problems, and consider how the One Health concept has been brought to bear on other issues, such as emerging new technologies. Ultimately, One Health is an important and worthwhile goal, and requires a debate that clarifies both the competing uses and the political nature of the project. PMID- 26817943 TI - IgG4-related sclerosing cholangitis: all we need to know. AB - Our knowledge and experience of IgG4-related sclerosing cholangitis (ISC) have expanded in the last decade. ISC is one of the common organ manifestations of IgG4-related disease (IgG4-RD); approximately 60 % of patients with this systemic condition have ISC in the proximal and/or distal bile ducts. ISC needs to be discriminated from primary sclerosing cholangitis, cholangiocarcinoma, and other rare forms of lymphoplasmacytic cholangiopathy (e.g., follicular cholangitis and sclerosing cholangitis with granulocytic epithelial lesions). Its diagnosis requires a multidisciplinary approach, in which serology, histology, and imaging play crucial roles. Treatments with high-dose corticosteroids typically lead to the rapid and consistent induction of disease remission. Another promising therapeutic approach is B-cell depletion with rituximab. Although disease relapse is relatively common, provided that appropriate treatments are administered, ISC is considered a "benign" disease with a low risk of liver failure and biliary malignancy. Its molecular pathology is characterized by Th2-dominant immune reactions, regulatory T-cell activation, and CCL1-CCR8 interactions. Particular subsets of B cells such as plasmablasts and regulatory B cells also expand. A recent global proteomic study demonstrated that three significantly activated immunological cascades in ISC were all B-cell- or immunoglobulin-related (Fc gamma receptor-mediated phagocytosis, B-cell receptor signaling pathway, and Fc epsilon receptor I signaling pathway), suggesting the crucial roles of B cells in the underlying immune reactions. Despite the expansion of our knowledge of the pathophysiology of ISC, the exact role of IgG4 remains unclear. A better understanding of its immunopathology will offer some potential drug targets for this emerging biliary disease. PMID- 26817945 TI - DETERMINATION OF THE INTERNAL EXPOSURE OF GREEK CITIZENS RETURNING FROM JAPAN IMMEDIATELY AFTER THE FUKUSHIMA ACCIDENT. AB - Following the nuclear accident at the Fukushima Daiichi Nuclear Power Plant on 11 March 2011, during the period 17 March to 25 October 2011, a total of 22 Greek citizens were measured after their return to Greece. Artificial radionuclides were detected in 5 of the 22 measured individuals by whole body counter measurements conducted 10 and 11 d after the commencement of the accident. Of the 5 contaminated individuals, 3 were adults and 2 children, aged 9 and 5 y, who stayed for a single day in Tokyo. Dose calculations were performed assuming that the sole exposure pathway was through inhalation that occurred on 14 March, according to the information provided by them, using the detected artificial radionuclides in the spectra ((134)Cs, (137)Cs, (131)I). The estimated total committed effective doses calculated were found to be in the range of 9-280 MUSv. PMID- 26817946 TI - Addressing Major Unmet Needs in Patients with Systolic Heart Failure: The Role of Ivabradine. AB - We reviewed clinical evidence for the use of ivabradine in systolic heart failure (HF), in which it appears to improve symptoms, improve quality of life, prevent hospitalization, and prolong survival, thereby addressing unmet needs in the management of HF. Ivabradine provides symptomatic benefits in HF on top of standard therapies, in terms of functional parameters and exercise capacity, and there is some evidence that this leads to improvements in quality of life in symptomatic HF patients, who may have dyspnea, altered exercise capacity, and fatigue. The SHIFT trial demonstrated that ivabradine has significant beneficial effects on major outcomes in HF. Ivabradine had a significant effect on pump failure death, which was reduced by 26 % (p = 0.014), with no effect on sudden cardiac death. This is an important result since pump failure death is currently the main cause of death in HF, and also because the reductions in mortality obtained with beta-blockers and spironolactone in the last 20 years appear to be mainly due to reduction in sudden death rather than reduction in pump failure death. Ivabradine also has a beneficial effect on hospital admissions (-26 %, p < 0.0001), which is clinically relevant since a quarter of HF patients can expect to be readmitted to hospital for HF within 1 month of discharge. Ivabradine treated patients are also at significantly lower risk of experiencing a second or third hospitalization for worsening HF. Ivabradine clearly has a key role to play in the management of HF by covering the main therapeutic objectives of symptoms, quality of life, and outcomes. PMID- 26817948 TI - Sacubitril Is Selectively Activated by Carboxylesterase 1 (CES1) in the Liver and the Activation Is Affected by CES1 Genetic Variation. AB - Sacubitril was recently approved by the Food and Drug Administration for use in combination with valsartan for the treatment of patients with heart failure with reduced ejection fraction. As a prodrug, sacubitril must be metabolized (hydrolyzed) to its active metabolite sacubitrilat (LBQ657) to exert its intended therapeutic effects. Thus, understanding the determinants of sacubitril activation will lead to the improvement of sacubitril pharmacotherapy. The objective of this study was to identify the enzyme(s) responsible for the activation of sacubitril, and determine the impact of genetic variation on sacubitril activation. First, an incubation study of sacubitril with human plasma and the S9 fractions of human liver, intestine, and kidney was conducted. Sacubitril was found to be activated by human liver S9 fractions only. Moreover, sacubitril activation was significantly inhibited by the carboxylesterase 1 (CES1) inhibitor bis-(p-nitrophenyl) phosphate in human liver S9. Further incubation studies with recombinant human CES1 and carboxylesterase 2 confirmed that sacubitril is a selective CES1 substrate. The in vitro study of cell lines transfected with wild-type CES1 and the CES1 variant G143E (rs71647871) demonstrated that G143E is a loss-of-function variant for sacubitril activation. Importantly, sacubitril activation was significantly impaired in human livers carrying the G143E variant. In conclusion, sacubitril is selectively activated by CES1 in human liver. The CES1 genetic variant G143E can significantly impair sacubitril activation. Therefore, CES1 genetic variants appear to be an important contributing factor to interindividual variability in sacubitril activation, and have the potential to serve as biomarkers to optimize sacubitril pharmacotherapy. PMID- 26817947 TI - How May Proton Pump Inhibitors Impair Cardiovascular Health? AB - Proton pump inhibitors (PPIs) are among the most widely used drugs worldwide. They are used to treat a number of gastroesophageal disorders and are usually prescribed as a long-term medication or even taken without a prescription. There are a number of clinical studies that associate PPI use with an increased cardiovascular risk. In this article, we review the clinical evidence for adverse cardiovascular effects of PPIs, and we discuss possible biological mechanisms by which PPIs can impair cardiovascular health. PMID- 26817949 TI - Biomarkers of Flutamide-Bioactivation and Oxidative Stress In Vitro and In Vivo. AB - The nonsteroidal androgen-receptor antagonist flutamide is associated with hepatic injury. Oxidative stress and reactive metabolite formation are considered contributing factors to liver toxicity. Here we have used flutamide as a model drug to study the generation of reactive drug metabolites that undergo redox cycling to induce oxidative stress (OS) in vitro and in vivo. Lipid peroxidation (LPO) markers, as well as genes regulated by the redox-sensitive Nrf2 pathway, have been identified as surrogates for the characterization of OS. These markers and metabolism biomarkers for drug bioactivation have been investigated to characterize drug-induced hepatic damage. Rat hepatocytes and in vivo studies showed that several LPO markers, namely the isoprostanes 15R-PD2, dihydro keto PE2, and iPF(2alpha)-VI, as well as hydroxynonenal mercapturic acid metabolites, had increased significantly by 24 hours after flutamide treatment from 4.9 to 15.3-fold in hepatocytes and from 2.6 to 31.0-fold in rat plasma. Induction of mRNA expression levels for Nrf2-regulated genes was evident as well, with heme oxygenase 1, glutathione-S-transferase pi1 and NAD(P)H dehydrogenase showing a 3.6-, 4.1-, and 1.9-fold increase in hepatocytes and 5.6-, 7.5-, and 94.1-fold in rat liver. All effects were observed at drug concentrations that did not show overt liver toxicity. Addition of an in situ hydrogen peroxide-generating system to in vitro experiments demonstrated the formation of a reactive di-imine intermediate as the responsible metabolic pathway for the generation of OS. The dataset suggests that hepatic oxidative stress conditions can be mediated via metabolic activation and can be monitored with suitable biomarkers preceding the terminal damage. PMID- 26817951 TI - Prevalence and correlates of sleep problems among elderly Singaporeans. AB - BACKGROUND: The current study examined the prevalence and correlates of sleep problems among elderly Singaporeans. METHODS: Data were taken from the Well-being of Singapore Elderly study, a cross-sectional, epidemiological survey conducted among Singapore residents aged 60 years and above (n = 2565). Respondents were screened for sleep problems through a series of questions in the Geriatric Mental State examination. Details on sociodemographic characteristics, physical activity, cognition, disability, chronic physical conditions, and depression were also collected. Logistic regression analysis was used to explore significant associations between sleep problems, sociodemographic characteristics, physical activity, cognition, disability, chronic physical conditions, and depression. RESULTS: Overall, 13.7% (n = 341) of older adults reported at least one sleep problem. Of those who reported sleep problems, 69.4% experienced sleep interruption at night, 48.9% reported having difficulty falling asleep, 22.3% reported early morning awakening, and 11.4% had all three problems. Elderly with sleep problems were significantly more likely to have a range of chronic physical conditions and depression and were also significantly less likely to be physically active. Older adults with at least one sleep problem reported significantly greater disability compared to those with no sleep problems. CONCLUSION: The high probability of comorbid chronic conditions as well as higher disability among those with sleep problems makes this an important area of research. PMID- 26817950 TI - Overlapping signatures of chronic pain in the DNA methylation landscape of prefrontal cortex and peripheral T cells. AB - We tested the hypothesis that epigenetic mechanisms in the brain and the immune system are associated with chronic pain. Genome-wide DNA methylation assessed in 9 months post nerve-injury (SNI) and Sham rats, in the prefrontal cortex (PFC) as well as in T cells revealed a vast difference in the DNA methylation landscape in the brain between the groups and a remarkable overlap (72%) between differentially methylated probes in T cells and prefrontal cortex. DNA methylation states in the PFC showed robust correlation with pain score of animals in several genes involved in pain. Finally, only 11 differentially methylated probes in T cells were sufficient to distinguish SNI or Sham individual rats. This study supports the plausibility of DNA methylation involvement in chronic pain and demonstrates the potential feasibility of DNA methylation markers in T cells as noninvasive biomarkers of chronic pain susceptibility. PMID- 26817952 TI - Essential and toxic elements in seaweeds for human consumption. AB - Essential elements (K, Ca, P, S, Cl, Mn, Fe, Cu, Zn, Ni, Br, and I) and nonessential or toxic elements (Al, Ti, Si, Rb, Sr, As, Cd, Sn, and Pb) were determined by energy-dispersive polarized x-ray fluorescence spectrometry in 14 seaweeds purchased in local specialty stores in Italy and consumed by humans. The differences in elements between the algae species reached up to 2-4 orders of magnitude. Lithothamnium calcareum showed the highest levels of Ca, Al, Si, Fe, and Ti. Palmaria palmata showed the highest concentrations of K, Rb, and Cl. The highest content of S was in Chondrus crispus. Laminaria digitata contained the highest concentrations of total As, Cd, Sn, Br, and I. The highest concentration of Zn was in Chlorella pyrenoidosa. Ulva lactuca displayed the highest levels of Cu, Ni, Mn, and Pb. Iodine levels ranged from 3.4 in Chlorella pyrenoidosa to 7316 mg/kg(dry) in Laminaria digitata. The nutrimental importance of essential elements was assessed using nutritional requirements. The results showed that the consumption of algae might serve as an important source of the essential elements. Health risk due to the toxic elements present in seaweed was estimated using risk estimators. Total As, Cd, and Pb concentrations ranged from <1 to 67.6, to 7.2 and to 6.7 mg/kg(dry) respectively; therefore, their contribution to total elemental intake does not appear to pose any threat to the consumers, but the concentrations of these elements should be controlled to protect the consumer against potential adverse health risks. PMID- 26817953 TI - Association of Child Abuse Exposure With Suicidal Ideation, Suicide Plans, and Suicide Attempts in Military Personnel and the General Population in Canada. AB - IMPORTANCE: Recent evidence indicates a high prevalence of child abuse exposure in modern US veterans, which may explain in part their higher likelihood of suicide relative to civilians. However, the relationship between child abuse exposure and suicide-related outcomes in military personnel relative to civilians is unknown. Furthermore, the associations among deployment-related trauma, child abuse exposure, and suicide-related outcomes in military personnel have not been examined. OBJECTIVES: To determine whether child abuse exposure is more prevalent in Canadian Armed Forces (CAF) personnel compared with the Canadian general population (CGP); to compare the association between child abuse exposure and suicidal ideation, suicide plans, and suicide attempts among the CAF and CGP; and to determine whether child abuse exposure has an additive or interaction effect on the association of deployment-related trauma and past-year suicidal ideation and suicide plans among Regular Forces personnel. DATA, SETTING, AND PARTICIPANTS: Data were collected from the following 2 nationally representative data sets: the 2013 Canadian Forces Mental Health Survey (CFMHS) for the CAF (8161 respondents; response rate, 79.8%) and the 2012 Canadian Community Health Survey-Mental Health (CCHS-MH) for the CGP (23,395 respondents; response rate, 68.9% [of these, 15,981 age-matched participants were drawn]). Data were collected from April 15 to August 31, 2013, for the CFMHS and January 2 to December 31, 2012, for the CCHS-MH. Data were analyzed from October 2014 to October 22, 2015. Statistical weights were applied to both data sets. MAIN OUTCOMES AND MEASURES: Child abuse exposure, including physical abuse, sexual abuse, and exposure to intimate partner violence, and deployment-related trauma were assessed in relation to suicide-related outcomes. RESULTS: Data were analyzed from 24 142 respondents aged 18 to 60 years (Regular Forces, 86.1% male and 13.9% female; Reserve Forces, 90.6% male and 8.9% female; and CGP, 49.9% male and 50.1% female). Any child abuse exposure was higher in the Regular Forces (47.7%; 95% CI, 46.4%-49.1%) and Afghanistan mission-deployed Reserve Forces (49.4%; 95% CI, 46.3%-51.5%) compared with the CGP (33.1%; 95% CI, 31.8%-34.4%). All types of child abuse exposures were associated with increased odds of suicidal ideation, suicide plans, and suicide attempts in the CGP (range of adjusted odds ratios [AORs], 3.0 [95% CI, 2.3-3.9] to 7.7 [95% CI, 5.7-10.3]; P < .05) and CAF (range of AORs, 1.7 [95% CI, 1.0-2.9] to 6.3 [95% CI, 4.2-9.5]; P < .05), with many associations significantly weaker in military personnel relative to civilians. Additive effects for past-year suicide ideation (AOR, 2.7; 95% CI, 1.8-4.2) and past-year suicide plans (AOR, 4.6; 95% CI, 2.3-9.2) but not interactive effects for past-year suicide ideation (AOR, 1.2; 95% CI, 0.7-2.2) and past-year suicide plans (AOR, 0.8; 95% CI, 0.3-2.2) were noted between deployment-related trauma and child abuse exposure among Regular Forces personnel. CONCLUSIONS AND RELEVANCE: Individuals with a child abuse history may be more likely to enter the military, and child abuse exposure may increase the likelihood of suicide-related outcomes. Prevention efforts targeting child abuse may reduce suicide-related outcomes. PMID- 26817954 TI - Activation of the thrombopoietin receptor by mutant calreticulin in CALR-mutant myeloproliferative neoplasms. AB - Recurrent somatic mutations of calreticulin (CALR) have been identified in patients harboring myeloproliferative neoplasms; however, their role in tumorigenesis remains elusive. Here, we found that the expression of mutant but not wild-type CALR induces the thrombopoietin (TPO)-independent growth of UT 7/TPO cells. We demonstrated that c-MPL, the TPO receptor, is required for this cytokine-independent growth of UT-7/TPO cells. Mutant CALR preferentially associates with c-MPL that is bound to Janus kinase 2 (JAK2) over the wild-type protein. Furthermore, we demonstrated that the mutant-specific carboxyl terminus portion of CALR interferes with the P-domain of CALR to allow the N-domain to interact with c-MPL, providing an explanation for the gain-of-function property of mutant CALR. We showed that mutant CALR induces the phosphorylation of JAK2 and its downstream signaling molecules in UT-7/TPO cells and that this induction was blocked by JAK2 inhibitor treatment. Finally, we demonstrated that c-MPL is required for TPO-independent megakaryopoiesis in induced pluripotent stem cell derived hematopoietic stem cells harboring the CALR mutation. These findings imply that mutant CALR activates the JAK2 downstream pathway via its association with c-MPL. Considering these results, we propose that mutant CALR promotes myeloproliferative neoplasm development by activating c-MPL and its downstream pathway. PMID- 26817955 TI - Thrombin-independent contribution of tissue factor to inflammation and cardiac hypertrophy in a mouse model of sickle cell disease. PMID- 26817956 TI - Reducing the hospital burden of heparin-induced thrombocytopenia: impact of an avoid-heparin program. AB - Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction occurring in up to 5% of patients exposed to unfractionated heparin (UFH). We examined the impact of a hospital-wide strategy for avoiding heparin on the incidence of HIT, HIT with thrombosis (HITT), and HIT-related costs. The Avoid-Heparin Initiative, implemented at a tertiary care hospital in Toronto, Ontario, Canada, since 2006, involved replacing UFH with low-molecular-weight heparin (LMWH) for prophylactic and therapeutic indications. Consecutive cases with suspected HIT from 2003 through 2012 were reviewed. Rates of suspected HIT, adjudicated HIT, and HITT, along with HIT-related expenditures were compared in the pre-intervention (2003 2005) and the avoid-heparin (2007-2012) phases. The annual rate of suspected HIT decreased 42%, from 85.5 per 10 000 admissions in the pre-intervention phase to 49.0 per 10 000 admissions in the avoid-heparin phase ( ITALIC! P< .001). The annual rate of patients with a positive HIT assay decreased 63% from 16.5 to 6.1 per 10 000 admissions ( ITALIC! P< .001), adjudicated HIT decreased 79% from 10.7 to 2.2 per 10 000 admissions ( ITALIC! P< .001), and HITT decreased 91% from 4.6 to 0.4 per 10 000 admissions ( ITALIC! P< .001). Hospital HIT-related expenditures decreased by $266 938 per year in the avoid-heparin phase. To the best of our knowledge, this is the first study demonstrating the success and feasibility of a hospital-wide HIT prevention strategy. PMID- 26817957 TI - Risk factors predictive of occult cancer detection in patients with unprovoked venous thromboembolism. AB - Risk factors predictive of occult cancer detection in patients with a first unprovoked symptomatic venous thromboembolism (VTE) are unknown. Cox proportional hazard models and multivariate analyses were performed to assess the effect of specific risk factors on occult cancer detection within 1 year of a diagnosis of unprovoked VTE in patients randomized in the Screening for Occult Malignancy in Patients with Idiopathic Venous Thromboembolism (SOME) trial. A total of 33 (3.9%; 95% CI, 2.8%-5.4%) out of the 854 included patients received a new diagnosis of cancer at 1-year follow-up. Age >= 60 years (hazard ratio [HR], 3.11; 95% CI, 1.41-6.89; ITALIC! P= .005), previous provoked VTE (HR, 3.20; 95% CI, 1.19-8.62; ITALIC! P= .022), and current smoker status (HR, 2.80; 95% CI, 1.24-6.33; ITALIC! P= .014) were associated with occult cancer detection. Age, prior provoked VTE, and smoking status may be important predictors of occult cancer detection in patients with first unprovoked VTE. This trial was registered atwww.clinicaltrials.govas #NCT00773448. PMID- 26817958 TI - Strategies that delay or prevent the timely availability of affordable generic drugs in the United States. AB - High cancer drug prices are influenced by the availability of generic cancer drugs in a timely manner. Several strategies have been used to delay the availability of affordable generic drugs into the United States and world markets. These include reverse payment or pay-for-delay patent settlements, authorized generics, product hopping, lobbying against cross-border drug importation, buying out the competition, and others. In this forum, we detail these strategies and how they can be prevented. PMID- 26817959 TI - Dense arrays of cobalt nanorods as rare-earth free permanent magnets. AB - We demonstrate in this paper the feasibility to elaborate rare-earth free permanent magnets based on cobalt nanorods assemblies with energy product (BH)max exceeding 150 kJ m(-3). The cobalt rods were prepared by the polyol process and assembled from wet suspensions under a magnetic field. Magnetization loops of dense assemblies with remanence to a saturation of 0.99 and squareness of 0.96 were measured. The almost perfect M(H) loop squareness together with electron microscopy and small angle neutron scattering demonstrate the excellent alignment of the rods within the assemblies. The magnetic volume fraction was carefully measured by coupling magnetic and thermogravimetric analysis and found in the range from 45 to 55%, depending on the rod diameter and the alignment procedure. This allowed a quantitative assessment of the (BH)max values. The highest (BH)max of 165 kJ m(-3) was obtained for a sample combining a high magnetic volume fraction and a very large M(H) loop squareness. This study shows that this bottom up approach is very promising to get new hard magnetic materials that can compete in the permanent magnet panorama and fill the gap between the ferrites and the NdFeB magnets. PMID- 26817960 TI - Concentration dependent effects of urea binding to poly(N-isopropylacrylamide) brushes: a combined experimental and numerical study. AB - The binding effects of osmolytes on the conformational behavior of grafted polymers are studied in this work. In particular, we focus on the interactions between urea and poly(N-isopropylacrylamide) (PNIPAM) brushes by monitoring the ellipsometric brush thickness for varying urea concentrations over a broad temperature range. The interpretation of the obtained data is supported by atomistic molecular dynamics simulations, which provide detailed insights into the experimentally observed concentration-dependent effects on PNIPAM-urea interaction. In particular, in the low concentration regime (cu <= 0.5 mol L(-1)) a preferential exclusion of urea from PNIPAM chains is observed, while in the high concentration regime (2 <= cu <= 7 mol L(-1)) a preferential binding of the osmolyte to the polymer surface is found. In both regimes, the volume phase transition temperature (Ttr) decreases with increasing urea concentration. This phenomenon derives from two different effects depending on urea concentration: (i) for cu <= 0.5 mol L(-1), the decrease of Ttr is explained by a decrease of the chemical potential of bulk water in the surrounding aqueous phase; (ii) for cu >= 2 mol L(-1), the lower Ttr is explained by the favorable replacement of water molecules by urea, which can be regarded as a cross-linker between adjacent PNIPAM chains. Significant effects of the concentration-dependent urea binding on the brush conformation are noticed: at cu = 0.5 mol L(-1), although urea is loosely embedded between the hydrated polymer chains, it enhances the brush swelling by excluded volume effects. Beyond 0.5 mol L(-1), the stronger interaction between PNIPAM and urea reduces the chain hydration, which in combination with cross-linking of monomer units induces the shrinkage of the polymer brush. PMID- 26817961 TI - Comparison of bronchial brushing and sputum in detection of pediatric pulmonary tuberculosis. AB - The retrospective study aimed to evaluate the diagnostic value of bronchial brushing and sputum using acid fast bacilli smear, mycobacterial culture and real time PCR in detection of pediatric pulmonary tuberculosis, sensitivity and specificity of bronchial brushing and sputum examined by the three methods were calculated and compared to each other. Data showed there were no significant difference in sensitivity between bronchial brushing and matched sputum using each method. But the specificity of real-time PCR on bronchial brushing was lower than on sputum. Compared with bronchial brushing, sputum was better specimen in detection of pediatric pulmonary tuberculosis. PMID- 26817962 TI - The impact of red blood cell transfusions on perioperative outcomes in the contemporary era of liver resection. AB - BACKGROUND: Perioperative red blood cell transfusions (RBCTs) are common in patients undergoing partial hepatectomy. We sought to explore the relationship between RBCTs and posthepatectomy perioperative outcomes in the contemporary surgical era. METHODS: We reviewed all patients undergoing partial hepatectomy from 2003 to 2012. Primary outcome was 30-day major morbidity (MM). We compared patients who did and received perioperative RBCT (defined as from time of operation until 30 days postoperatively. Multivariate analysis was performed to identify factors associated with MM and duration of stay, using logistic and negative binomial regression. RESULTS: Among 712 patients, 16.8% experienced MM, of whom 53.3% received RBCT. Patients who received RBCT experienced MM more commonly (30.8% vs 11.1%; P < .001). On multivariate analysis, the only factors associated with MM were age (relative risk [RR], 1.03; 95% CI, 1.00-1.06), greater operative time (RR, 1.29; 95% CI, 1.11-1.50), and RBCT (RR, 3.57; 95% CI, 1.81-7.04). RBCT was associated independently with a greater duration of stay (RR, 1.47; 95% CI, 1.13-1.91). CONCLUSION: Receipt of RBCT is associated independently with perioperative MM and prolonged hospitalization after partial hepatectomy. These findings further the rationale supporting the need for a strategy of blood management to decrease the use of RBCT after hepatectomy. PMID- 26817964 TI - Genotypic Heterogeneity and the Mode of Inheritance in Epidermolysis Bullosa. PMID- 26817963 TI - Application of near-infrared fluorescence imaging during modified associating liver partition and portal vein ligation for staged hepatectomy. PMID- 26817965 TI - The Influence of Vagus Nerve and Spinal Cord Stimulation on the Ictal Fast Ripple Activity in a Spike-and-Wave Rat Model of Seizures. AB - OBJECTIVES: Fast ripple (FR) activity has received increasing attention as a potential epileptic marker. The current knowledge on how neurostimulation affects FRs is, however, very limited. In this study, we assess the influence of the vagus nerve stimulation (VNS) and spinal cord stimulation (SCS) frequency on ictal FRs associated with spike-and-wave (SW) seizures. METHODS: SW discharges were induced and maintained by an infusion of pentylenetetrazol in rat. During ongoing SW seizures, SCS was conducted at 30, 80, 130, and 180 Hz and VNS at 10, 30, 80, 130, and 180 Hz. The FRs were derived from intracortical recordings and the FR rate was used for quantifying the level of FR activity. RESULTS: The FR rate was significantly correlated (r = 0.81) with the level of total pentylenetetrazol dose. Compared with no stimulation intervals, SCS conducted at 80, 130, and 180 Hz significantly reduced the normalized FR rate by 24, 38, and 44%, respectively. Similarly, VNS conducted at 30, 80, 130, and 180 Hz significantly reduced the normalized FR rate by 23, 40, 61, and 65%, respectively. CONCLUSIONS: In the present model of sustained SW seizures, the FR rate was proportional with the severity of the SW seizures. Both SCS and VNS attenuated the FR rate and this attenuation was consistently strongest at the higher stimulation frequencies. Our results suggest that SCS may induce some of the same antiepileptic effects as VNS. PMID- 26817966 TI - Thrombus-in-Transit Following Watchman Device Implantation. AB - Thrombus-in-transit crossing an interatrial communication is a rare but potentially serious clinical condition, which has so far not been described after implantation of left atrial appendage (LAA) closure devices. Here, we describe the case of a 76-year-old woman with permanent atrial fibrillation and contraindication for oral anticoagulation therapy, who developed pericardial tamponade and acute pulmonary embolism with visible thrombus-in-transit formation following LAA closure. Most likely manipulation of the Watchman device in the LAA during two failed attempts in device positioning led to pericardial tamponade and venous puncture, manual compression after completion of the procedure and further immobilization resulted in deep vein thrombosis with consecutive pulmonary embolism and thrombus-in-transit formation. This case highlights the value of echocardiography after LAA closure. PMID- 26817967 TI - Editorial--Authorship. PMID- 26817968 TI - Methodology of Nursing Studies Based on Islamic Documents. PMID- 26817969 TI - Interpersonal violence in road rage. Cases from the Medico-Legal Center for Victims of Violence in Hamburg. AB - Aggressive behavior in traffic is a widespread phenomenon. Up to 90% of the population are involved in mild forms such as shouting or gesturing. More dramatic cases with injury to individuals affect at least 1100 people in the US annually. Certain factors such as a male sex, a young age and an urban residency have been identified to contribute to the likelihood of road rage. Central to this analysis is the determination of specific features regarding the conflicting parties, the crime scene and the injury pattern in violent offenses related to traffic. In a retrospective study spanning 10 years, cases of road rage-linked injuries were identified amongst patients at the Medico-Legal Center of the Institute of Legal Medicine in Hamburg, Germany. The data were digitized and then analyzed using descriptive statistics via SPSS. There are disproportionately large numbers of males (85.7%) and motorists (61.2%) amongst road rage perpetrators. Usually the conflicting parties have no prior relationship (89.7%). In 68.1% of the cases, the violence applied was exclusively physical. Objects were utilized in 31.0% of all cases, and in more than half (55.6%) of these cases the vehicle was used as a weapon. The resulting trauma in road rage is mostly blunt and applied to the face and the extremities. There are characteristic features regarding the demographics, time and place of incident, as well as severity and pattern of injury in road rage associated offenses. Identifying these factors may lead to appropriate measures in the reduction of road rage. PMID- 26817970 TI - Determination of sex from the hyoid bone in a contemporary White population. AB - Six discriminant functions, developed from an historic White population, were tested on a contemporary White population for determination of sex from the hyoid. One hundred and thirty four fused and unfused hyoids from a contemporary White population were used. Individuals ranged between 20 and 49 years old. Six historic White discriminant functions were applied to the fused and unfused hyoids of the pooled contemporary White population, i.e. all males and females and all age ranges combined. The overall accuracy rates were between 72.1% and 92.3%. Correct sex determination for contemporary White males ranged between 88.2% and 96.3%, while correct sex determination for contemporary White females ranged between 31.3% and 92.0%. Discriminant functions were created for the contemporary White population with overall mean accuracy rates between 67.0% and 93.0%. The multivariate discriminant function overall accuracy rates were between 89.0% and 93.0% and the univariate discriminant function overall accuracy rates were between 67.0% and 86.8%. The contemporary White population data were compared to other populations and showed significant differences between many of the variables measured. This study illustrated the need for population-specific and temporally-specific discriminant functions for determination of sex from the hyoid bone. PMID- 26817971 TI - Efficacy of Common Analgesics for Postsurgical Pain in Rats. PMID- 26817972 TI - Microsurgical and Percutaneous Epididymal Sperm Aspiration for Sperm Collection from Live Mice. PMID- 26817974 TI - Blood Lactate Concentrations in Gottingen Minipigs Compared with Domestic Pigs. AB - Measurement of the blood lactate concentration is a useful monitoring tool during anesthesia of animals and people. Recently, blood lactate has been used to monitor anesthetized pigs, but very little is known about variations in blood lactate concentrations in this species. We therefore evaluate the effects of breed (domestic pigs compared with Gottingen minipigs), body weight (domestic pigs of 40 kg compared with 70 kg), type of anesthesia (inhalation compared with infusion) and surgery (minor compared with major surgery) on blood lactate concentrations in pigs. Anesthesia reports from 81 pigs are included. We find significantly higher blood lactate levels in minipigs anesthetized with isofluorane (2.53 +/- 1.10 mmol/L) compared with domestic pigs (0.68 +/- 0.48 mmol/L). Body weight, type of anesthesia, and type of surgery had no effect on blood lactate levels. Therefore, reference values for blood lactate concentrations in pigs should reflect the breed of interest. PMID- 26817973 TI - The Biology and Husbandry of the African Spiny Mouse (Acomys cahirinus) and the Research Uses of a Laboratory Colony. AB - African spiny mice (Acomys spp.) are unique precocial rodents that are found in Africa, the Middle East, and southern Asia. They exhibit several interesting life history characteristics, including precocial development, communal breeding, and a suite of physiologic adaptations to desert life. In addition to these characteristics, African spiny mice are emerging as an important animal model for tissue regeneration research. Furthermore, their important phylogenetic position among murid rodents makes them an interesting model for evolution and development studies. Here we outline the necessary components for maintaining a successful captive breeding colony, including laboratory housing, husbandry, and health monitoring aspects. We also review past and present studies focused on spiny mouse behavior, reproduction, and disease. Last, we briefly summarize various current biomedical research directions using captive-bred spiny mice. PMID- 26817975 TI - Rat Breeding Parameters According to Floor Space Available in Cage. AB - The cage floor space recommended for a female rat with a litter is greater in the 8th edition of the Guide for the Care and Use of Laboratory Animals than in previous editions. As a result, research institutions using commonly available cages to house rats may not offer the recommended amount of space for a breeding pair and litter housed in the same cage. We evaluated breeding parameters in rats housed in cages with 143 in(2) (922.6 cm(2)) compared with 210 in(2) (1355 cm(2)) of floor space. Given the strains of rats typically used at our institution, a monogamous breeding pair and litter requires 164 in(2) (1058.1 cm(2)) of floor space according to the Guide. Pairs of breeding animals were housed in each type of cage; and average time between litters, number of litters born, percentage of litter weaned, numbers of pups born and weaned, and average weaning weights were evaluated. None of the breeding parameters evaluated differed according to the floor space of the cage in which the rats were housed. PMID- 26817976 TI - Effect of 2 Bedding Materials on Ammonia Levels in Individually Ventilated Cages. AB - This study sought to identify an optimal rodent bedding and cage-change interval to establish standard procedures for the IVC in our rodent vivarium. Disposable cages were prefilled with either corncob or alpha-cellulose bedding and were used to house 2 adult Sprague-Dawley rats (experimental condition) or contained no animals (control). Rats were observed and intracage ammonia levels measured daily for 21 d. Intracage ammonia accumulation became significant by day 8 in experimental cages containing alpha-cellulose bedding, whereas experimental cages containing corncob bedding did not reach detectable levels of ammonia until day 14. In all 3 experimental cages containing alpha-cellulose, ammonia exceeded 100 ppm (our maximum acceptable limit) by day 11. Two experimental corncob cages required changing at days 16 and 17, whereas the remaining cage containing corncob bedding lasted the entire 21 d without reaching the 100-ppm ammonia threshold. These data suggests that corncob bedding provides nearly twice the service life of alpha-cellulose bedding in the IVC system. PMID- 26817977 TI - Validation of a Behavioral Ethogram for Assessing Postoperative Pain in Guinea Pigs (Cavia porcellus). AB - Although guinea pigs (Cavia porcellus) have been used in research for more than a century and remain the most prevalent USDA-covered species, little has been elucidated regarding the recognition of clinical pain or analgesic efficacy in this species. We sought to assess pain in guinea pigs by using newer, clinically relevant methods that have been validated in other rodent species: the behavioral ethogram and cageside proxy indicator. In this study, 10 male guinea pigs underwent electronic von Frey testing of nociception, remote videorecording of behavior, and cageside assessment by using time-to-consumption (TTC) of a preferred treat test. These assessments were performed across 2 conditions (anesthesia only and castration surgery under anesthesia) at 3 time points (2, 8, and 24 h after the event). The anesthesia only condition served to control for the nonpainful but potentially distressing components of the surgical experience. Compared with those after anesthesia only conditions, subtle body movements were increased and nociceptive thresholds were decreased at 2 and 8 h after surgery. At 24 h, neither subtle body movement behaviors nor nociceptive thresholds differed between the 2 conditions. In contrast, TTC scores did not differ between the anesthesia only and surgery conditions at any time point, underscoring the challenge of identifying pain in this species through cageside evaluation. By comparing ethogram scores with measures of nociception, we validated select behaviors as pain-specific. Therefore, our novel ethogram allowed us to assess postoperative pain and may further serve as a platform for future analgesia efficacy studies in guinea pigs. PMID- 26817978 TI - Review of Practices Reported for Preoperative Food and Water Restriction of Laboratory Pigs (Sus scrofa). AB - The traditionally cited recommendations for the preoperative restriction of food (including bedding) and water in pigs do not appear to be evidence-based. As a preliminary step in elucidating a rationale for and standardizing preoperative food and water restriction (PFWR), this structured review recorded recent reported practices in PFWR in laboratory pigs and its consequences. Medline, Google Scholar and Web of Science databases were searched for recently published (2012 - 2014) recovery surgery procedures in pigs. Information pertaining to PFWR practices, as delineated in the ARRIVE guidelines, was extracted from the 233 articles retrieved. Food withdrawal was described in 73 of the 233 (31%) papers evaluated, bedding withdrawal in 5 articles (2%), and water withholding in 13 publications (6%) papers. Food, bedding, and water withdrawal regimens had a median (range) duration of 12 (4 to 48), 48 (48 to 72), and 12 (2 to 12) h, respectively. Compared with other types of procedures, articles describing gastrointestinal or abdominal surgery were more likely to report fasting regimes. Liquid diets were described in 11 of the 233 (5%) publications evaluated. Adverse effects of PFWR effects were not reported. These data reveal considerable variation in PFWR practices. The stress of fasting coupled with the absence of evidence for current recommendations makes the rationale and standards for PFWR in pigs worthy of further study. PMID- 26817979 TI - Variation in Behavioral Reactivity Is Associated with Cooperative Restraint Training Efficiency. AB - Training techniques that prepare laboratory animals to participate in testing via cooperation are useful tools that have the potential to benefit animal wellbeing. Understanding how animals systematically vary in their cooperative training trajectories will help trainers to design effective and efficient training programs. In the present report we document an updated method for training rhesus monkeys to cooperatively participate in restraint in a 'primate chair.' We trained 14 adult male macaques to raise their head above a yoke and accept yoke closure in an average of 6.36 training days in sessions that lasted an average of 10.52 min. Behavioral observations at 2 time points prior to training (approximately 3 y and 1.3 y prior) were used to quantify behavioral reactivity directed toward humans and toward other macaques. Individual differences in submissive-affiliative reactivity to humans but not reactivity toward other monkeys were related to learning outcomes. Macaques that were more reactive to humans were less willing to participate in training, were less attentive to the trainer, were more reactive during training sessions, and required longer training sessions, longer time to yoke, and more instances of negative reinforcement. These results suggest that rhesus macaques can be trained to cooperate with restraint rapidly and that individual difference data can be used to structure training programs to accommodate variation in animal temperament. PMID- 26817980 TI - Developing a Comprehensive Animal Care Occupational Health and Safety Program at a Land-Grant Institution. AB - The Public Health Service Policy on the Humane Care and Use of Laboratory Animals and sound ethical practices require institutions to provide safe working environments for personnel working with animals; this mandate is achieved in part by establishing an effective animal care Occupational Health and Safety Program (OHSP). Land-grant institutions often face unique organizational challenges in fulfilling this requirement. For example, responsibilities for providing health and safety programs often have historically been dispersed among many different divisions scattered around the campus. Here we describe how our institutional management personnel overcame organizational structure and cultural obstacles during the formation of a comprehensive campus-wide animal care OHSP. Steps toward establishing the animal care OHSP included assigning overall responsibility, identifying all stakeholders, creating a leadership group, and hiring a fulltime Animal Care OHSP Specialist. A web-based portal was developed, implemented, and refined over the past 7 y and reflected the unique organizational structures of the university and the needs of our research community. Through this web-based portal, hazards are identified, risks are assessed, and training is provided. The animal care OHSP now provides easy mandatory enrollment, supports timely feedback regarding hazards, and affords enrollees the opportunity to participate in voluntary medical surveillance. The future direction and development of the animal care OHSP will be based on the research trends of campus, identification of emerging health and safety hazards, and ongoing evaluation and refinement of the program. PMID- 26817981 TI - Surveillance of a Ventilated Rack System for Corynebacterium bovis by Sampling Exhaust-Air Manifolds. AB - Corynebacterium bovis causes an opportunistic infection of nude (Foxn1, nu/nu) mice, leading to nude mouse hyperkeratotic dermatitis (scaly skin disease). Enzootic in many nude mouse colonies, C. bovis spreads rapidly to naive nude mice, despite modern husbandry practices, and is very difficult to eradicate. To facilitate rapid detection in support of eradication efforts, we investigated a surveillance method based on quantitative real-time PCR (qPCR) evaluation of swabs collected from the horizontal exhaust manifold (HEM) of an IVC rack system. We first evaluated the efficacy of rack sanitation methods for removing C. bovis DNA from the HEM of racks housing endemic colonies of infected nude mice. Pressurized water used to flush the racks' air exhaust system followed by a standard rack-washer cycle was ineffective in eliminating C. bovis DNA. Only after autoclaving did all sanitized racks test negative for C. bovis DNA. We then measured the effects of stage of infection (early or established), cage density, and cage location on the rack on time-to-detection at the HEM. Stage of infection significantly affected time-to-detection, independent of cage location. Early infections required 7.3 +/- 1.2 d whereas established infections required 1 +/- 0 d for detection of C. bovis at the HEM. Cage density influenced the quantity of C. bovis DNA detected but not time-to-detection. The location of the cage on the rack affected the time-to-detection only during early C. bovis infections. We suggest that qPCR swabs of HEM are useful during the routine surveillance of nude mouse colonies for C. bovis infection. PMID- 26817982 TI - Efficacy of Sustained-Release Buprenorphine in an Experimental Laparotomy Model in Female Mice. AB - Mice purportedly require dosing with the opioid buprenorphine (Bup-HCl) at least every 8 to 12 h to maintain an adequate plane of analgesia. Here we used an experimental laparotomy model to determine the clinical efficacy of sustained release formulations of buprenorphine (Bup-SR) after surgery in mice. Female CD1 mice underwent laparotomy and received either Bup-SR (0.6 mg/kg), Bup-HCl (0.1 mg/kg every 12 h), or saline (every 12 h). Pain was assessed at 1, 3, 6, 12, 24, 48, and 72 h according to the frequency of several behaviors (general activity, wheel-running activity, rearing, grooming, wound licking, orbital tightening, and percentage of integrated nest material) and daily body weight. Over time, wheel running was increased and wound licking was decreased in Bup-SR-treated mice compared with Bup-HCl- and saline-treated mice. Compared with Bup-HCl- and saline treated mice, Bup-SR-treated mice had increased general activity and percentage of integrated nest material and decreased orbital tightening for 1 to 6 h after surgery. The Bup-HCl- and saline-treated mice had similar general activity, orbital tightening scores, and wheel running activity. Rearing activity and body weight did not differ throughout the study, and none of the observed behaviors differed between groups at 24, 48, and 72 h after surgery. These results suggest that Bup-SR at 0.6 mg/kg provides adequate analgesia after laparotomy in mice and can be used as an alternative analgesic in this context. Furthermore, Bup-HCl at 0.1 mg/kg every 12 h may be inadequate in providing analgesia for abdominal procedures in mice. PMID- 26817983 TI - Analgesic Activity of Tramadol and Buprenorphine after Voluntary Ingestion by Rats (Rattus norvegicus). AB - Effective pain management for rats and mice is crucial due to the continuing increase in the use of these species in biomedical research. Here we used a recently validated operant orofacial pain assay to determine dose-response curves for buprenorphine and tramadol when mixed in nut paste and administered to male and female rats. Statistically significant analgesic doses of tramadol in nut paste included doses of 20, 30, and 40 mg/kg for female rats but only 40 mg/kg for male rats. For male rats receiving buprenorphine mixed in nut paste, a significant analgesic response was observed at 0.5 and 0.6 mg/kg. None of the doses tested produced a significant analgesic response in female rats. Our results indicate that at the doses tested, tramadol and buprenorphine produced an analgesic response in male rats. In female rats, tramadol shows a higher analgesic effect than buprenorphine. The analgesic effects observed 60 min after administration of the statistically significant oral doses of both drugs were similar to the analgesic effects of 0.03 mg/kg subcutaneous buprenorphine 30 min after administration. The method of voluntary ingestion could be effective, is easy to use, and would minimize stress to the rats during the immediate postoperative period. PMID- 26817985 TI - The Suitability of Propofol Compared with Urethane for Anesthesia during Urodynamic Studies in Rats. AB - Urethane anesthesia preserves many reflex functions and is often the preferred anesthetic for urodynamic studies in rats. Because of the toxicity profile of urethane, its use as an anesthetic typically is limited to acute and terminal investigations. Alternative anesthetic options are needed for longitudinal studies of micturition reflexes in rats. In this study, we evaluated propofol anesthesia administered at constant rate infusion at different planes of anesthesia in rats for combined cystometrography and external urethral sphincter (EUS) EMG in rats. No reflex micturition was noted after rats received 100%, 80%, or 60% of a previously reported anesthetic dose of propofol. At 40% of the standard propofol dose, a subset of rats showed reflex voiding, with bladder contractions and associated EUS EMG activity. In contrast, urethane anesthesia at a surgical plane allowed for reflex voiding with bladder contractions and EUS activation. Latency to leaking or voiding was longer in rats under propofol anesthesia than in those under urethane anesthesia. In a subset of rats with reflex voiding under propofol anesthesia, voiding efficiency was decreased compared with that of rats anesthetized with urethane. We conclude that propofol anesthesia suppresses micturition reflexes in rats more efficiently than did urethane. Propofol is a suitable anesthetic for longitudinal studies in rats, but its use for urodynamic evaluations is limited in these animals due to its marked suppression of both bladder contractions and EUS EMG activation. PMID- 26817986 TI - Twenty-four-Hour Measurement of Intraocular Pressure in Guinea Pigs (Cavia porcellus). AB - The objective of this study was to measure intraocular pressure (IOP) in intact, healthy guinea pigs (15 male, 15 female) every 2 h for a 24-h period. First, IOP was measured by using rebound tonometry (RBT). After a 1-min rest period, 0.5% proparacaine ophthalmic solution, a topical anesthetic, was applied to both eyes; 4 min after anesthetic instillation, IOP was measured by using applanation tonometry (APT). The IOP was lower during the light period (0700 to 1900) than during the dark phase (2000 to 0600). The lowest IOP by both RBT and APT (3.68 and 13.37 mm Hg, respectively) occurred at 0700, whereas maximal IOP occurred at 2300 for RBT (8.12 mm Hg) but at 2100 for APT (20.62 mm Hg). No significant differences in IOP between the left and right eyes or between RBT and APT were noted. In addition, daily variations in the IOP of guinea pigs seem to be independent of sex and body weight. The results of this study may be beneficial in the diagnosis and observation of glaucoma in guinea pigs. PMID- 26817984 TI - The Physiologic Effects of Isoflurane, Sevoflurane, and Hypothermia Used for Anesthesia in Neonatal Rats (Rattus norvegicus). AB - Information regarding effective anesthetic regimens for neonatal rat pups is limited. Here we investigated whether isoflurane or sevoflurane anesthesia maintains physiologic parameters more consistently than does hypothermia anesthesia in neonatal rat pups. Rat pups (age, 4 d) were randomly assigned to receive isoflurane, sevoflurane, or hypothermia. Physiologic parameters monitored at 1, 5, 10, and 15 min included heart rate (HR), respiratory rate (RR), and oxygen saturation (%SpO2). Other parameters evaluated were loss and return of righting reflex, paw withdrawal reflex, and maternal acceptance. Corticosterone and glucose were sampled at 20 min and 24 h after anesthesia induction. Once a surgical plane of anesthesia was achieved, a skin incision was made on the right lateral thigh. After the procedure, all pups were accepted and cared for by their dam. Isoflurane- and sevoflurane-treated pups maintained higher HR, RR, %SpO2, and glucose levels than did hypothermia-treated pups. For both the isoflurane and sevoflurane groups, HR and RR were significantly lower at 10 and 15 min after anesthesia than at 1 min. Compared with hypothermia, isoflurane and sevoflurane anesthesia provided shorter times to loss of and return of the righting reflex. Although corticosterone did not differ among the groups, glucose levels were higher at 20 min after anesthesia induction than at 24 h in all anesthetic groups. We conclude that both isoflurane and sevoflurane anesthesia maintain physiologic parameters (HR, RR, %SpO2) more consistently than does hypothermia anesthesia in 4-d-old rat pups. PMID- 26817987 TI - An Incidence of Pseudopregnancy Associated with the Social Enrichment of Rabbits (Oryctolagus cuniculi). AB - Here we describe a case of pseudopregnancy in a New Zealand White rabbit as a result of pair housing with an aggressive conspecific. Clinical signs included fur pulling and nest building that developed shortly after separation from the aggressor. An ovariohysterectomy was performed, and histopathologic findings support the diagnosis of pseudopregnancy. When introducing adult female rabbits to pair housing, stable pairs may be difficult to achieve because of the dominance-associated behavior that can occur as hierarchal relationships are formed. Does that are pair-housed after puberty should be monitored for aggressive behavior. PMID- 26817988 TI - Redox status in workers occupationally exposed to long-term low levels of ionizing radiation: A pilot study. AB - OBJECTIVES: Reactive oxygen species (ROS), including superoxide (O2(*-)), play an important role in the biological effects of ionizing radiation. The human body has developed different antioxidant systems to defend against excessive levels of ROS. The aim of the present study is to investigate the redox status changes in the blood of radiologic technologists and compare these changes to control individuals. METHODS: We enrolled 60 medical workers: 20 occupationally exposed to ionizing radiation (all radiologic technologists), divided in three subgroups: conventional radiography (CR), computerized tomography (CT), and interventional radiography (IR) and 40 age- and gender-matched unexposed controls. Levels of O2(*-) and malondialdehyde (MDA) in blood were measured as an index of redox status, as were the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase. Redox status was also assessed by measuring levels of reduced and oxidized glutathione (GSH, GSSG, respectively). RESULTS: Levels of O2(*-) and MDA, and SOD activity in the blood of IR and CT-exposed subjects were significantly higher than both the CR-exposed subjects and control individuals. However, there were no statistically significant differences in the levels of catalase, GSH and ratio of GSH/GSSG between exposed workers and control individuals. DISCUSSION: This study suggests that healthcare workers in CT and IR occupationally exposed to radiation have an elevated circulating redox status as compared to unexposed individuals. PMID- 26817989 TI - Hospitalization for transurethral bladder resection reduces quality of life in Danish patients with non-muscle-invasive bladder tumour. AB - Objective The aim of the study was to evaluate the impact of transurethral resection of bladder tumour (TURBT) on patients' quality of life (QoL) and to validate a tool to quantify problems associated with TURBT in a Danish population. Materials and methods A prospective study was carried out using a combination of questionnaires and interviews. The study included 165 consecutive patients undergoing a TURBT owing to non-muscle-invasive bladder cancer (NMIBC) from 1 May 2011 to 30 April 2012. Seven patients were selected for interviews. The Danish translation of the QLQ-NMIBC24 Quality of Life Questionnaire for NMIBC, from the European Organisation for Research and Treatment of Cancer (EORTC), was used. The interviews were semi-structured. The reliability of the subscales quantifying QoL as defined by the EORTC was tested by computing Cronbach's coefficient alpha and confirmatory factor analysis. The interviews were analysed using the phenomenological method. Results The questionnaire was returned by 121 (77%) patients at a mean of 12 days after hospital discharge. Over half had substantial voiding problems and one-third had emotional concerns. These results were confirmed by the interviews. The mean +/- SD score for urinary symptoms was 45.21 +/- 23.9 and the mean score for the future worries subscale was 39.9 +/- 29.9. Cronbach's coefficient alpha was 0.84 for the urinary symptom subscale and 0.93 for the future worries subscale, which satisfied the reliability criterion for clinical use. Conclusions This first prospective study on QoL following TURBT in patients with NMIBC shows that TURBT has a significant impact on QoL. The Danish version of the EORTC questionnaire QLQ-NMIBC24 has been validated and confirmed in a Danish population. PMID- 26817990 TI - Cationic ruthenium alkylidene catalysts bearing phosphine ligands. AB - The discovery of highly active catalysts and the success of ionic liquid immobilized systems have accelerated attention to a new class of cationic metathesis catalysts. We herein report the facile syntheses of cationic ruthenium catalysts bearing bulky phosphine ligands. Simple ligand exchange using silver(i) salts of non-coordinating or weakly coordinating anions provided either PPh3 or chelating Ph2P(CH2)nPPh2 (n = 2 or 3) ligated cationic catalysts. The structures of these newly reported catalysts feature unique geometries caused by ligation of the bulky phosphine ligands. Their activities and selectivities in standard metathesis reactions were also investigated. These cationic ruthenium alkylidene catalysts reported here showed moderate activity and very similar stereoselectivity when compared to the second generation ruthenium dichloride catalyst in ring-closing metathesis, cross metathesis, and ring-opening metathesis polymerization assays. PMID- 26817991 TI - Computational Insights into the Different Resistance Mechanism of Imidacloprid versus Dinotefuran in Bemisia tabaci. AB - Insecticide resistance is a critical problem for pest control and management. For Bemisia tabaci, striking high metabolic resistance (generally conferred by CYP6CM1) was observed for imidacloprid (IMI) and most other neonicotinoid members. However, dinotefuran (DIN) displayed very low resistance factors, which indicated distinct metabolic properties. Here, molecular modeling methods were applied to explore the different resistance features of IMI versus DIN within the Q type of CYP6CM1. It was found that Arg225 played crucial roles in the binding of IMI-CYP6CM1vQ with a cation-pi interaction and two stable H-bonds; however, such interactions were all absent in the DIN-CYP6CM1vQ system. The stable binding of IMI with CYP6CM1vQ would facilitate the following metabolic reaction, while the weak binding of DIN might disable its potential metabolism, which should be an important factor for their distinct resistance levels. The findings might facilitate future design of the antiresistance neonicotinoid molecules. PMID- 26817992 TI - Electroreflectance imaging of gold-H3PO4 supercapacitors. Part I: experimental methodology. AB - Electroreflectance microscopy is demonstrated as a high-resolution, non-contact method to image dynamic charge distribution in integrated microsupercapacitor structures during fast voltage cycling. Electroreflectance camera images of a gold electrode H3PO4 polymer electrolyte microsupercapacitor reveal time varying charge distribution with submicron spatial resolution, millisecond time resolution, and electroreflectance resolution on the order of 500 nC cm(-2). A model describing changes in the metal electrode's optical constants as a function of free electron concentration shows good agreement with measured electroreflectance. The proposed method can be used for sensitive, non-contact measurements of charge spatial distribution, and defect and performance characterization in electrode-electrolyte microdevices. PMID- 26817993 TI - In the Biosimilar Marketplace Will There Be 50 Ways to Leave Your Insulin? AB - The future biosimilar insulin marketplace could be a bane, benefit, or something in between, to patients under our care in the United States. Formulary preferred product status, with or without FDA interchangeability designation, coupled with current and proposed state pharmacy substitution laws may lead to an environment with as many as 50 different substitution guidelines depending on in which state a patient presents his or her prescription to be filled. If online global prescription supply options, often referred to as "Canada Drug," are utilized, other country substitution guidelines come into play, which may yield a recipe for confusion, if not disaster. PMID- 26817994 TI - The solution configurations of inactive and activated DntR have implications for the sliding dimer mechanism of LysR transcription factors. AB - LysR Type Transcriptional Regulators (LTTRs) regulate basic metabolic pathways or virulence gene expression in prokaryotes. Evidence suggests that the activation of LTTRs involves a conformational change from an inactive compact apo- configuration that represses transcription to an active, expanded holo- form that promotes it. However, no LTTR has yet been observed to adopt both configurations. Here, we report the results of structural studies of various forms of the LTTR DntR. Crystal structures of apo-DntR and of a partially autoinducing mutant H169T DntR suggest that active and inactive DntR maintain a compact homotetrameric configuration. However, Small Angle X-ray Scattering (SAXS) studies on solutions of apo-, H169T- and inducer-bound holo-DntR indicate a different behaviour, suggesting that while apo-DntR maintains a compact configuration in solution both H169T- and holo-DntR adopt an expanded conformation. Models of the SAXS-obtained solution conformations of apo- and holo-DntR homotetramers in complex with promoter-operator region DNA are consistent with previous observations of a shifting of LTTR DNA binding sites upon activation and a consequent relaxation in the bend of the promoter-operator region DNA. Our results thus provide clear evidence at the molecular level which strongly supports the 'sliding dimer' hypothesis concerning LTTR activation mechanisms. PMID- 26817995 TI - Prospective Evaluation of Cetuximab-Mediated Antibody-Dependent Cell Cytotoxicity in Metastatic Colorectal Cancer Patients Predicts Treatment Efficacy. AB - Cetuximab is a monoclonal antibody to the EGFR that induces antibody-dependent cell cytotoxicity (ADCC) through Fcgamma receptors on immune cells. Although SNPs in genes encoding Fcgamma receptors are functionally relevant to cetuximab mediated ADCC in colorectal cancer, a direct correlation between in vitro ADCC and clinical response to cetuximab is not defined. We therefore enrolled 96 consecutive metastatic colorectal cancer (mCRC) patients at diagnosis in a study that assessed FcgammaR status and cetuximab-mediated ADCC. Patients carrying the FcgammaRIIa H alleles 131H/Hand 131H/R had significantly higher ADCC compared with patients with the 131R/R alleles (P= 0.013). Patients carrying FcgammaRIIIa genotypes with the V alleles 158V/V and 158V/F displayed higher ADCC compared with patients carrying the 158F/F genotype (P= 0.001). Progression-free survival of patients with an FcgammaRIIIa 158V allele was significantly longer compared with patients carrying 158F/F (P= 0.05), whereas no significant difference was observed for overall survival. Twenty-eight of 50 mCRC patients with wild-type KRAS received cetuximab. The average ADCC-mediated killing was 30% of assay targets for patients who experienced cetuximab complete or partial response, 21% in patients with stable disease and 9% in patients with progressive disease. To characterize basal natural killer (NK) activity, cytotoxicity was evaluated in 39 of 96 mCRC patients. Patients who responded to first-line treatment had higher NK cell cytotoxicity. Thus, although limited to this cohort of patients, in vitro cetuximab-mediated ADCC correlated with FcgammaR polymorphisms and predicted cetuximab responsiveness. PMID- 26817996 TI - Synergistic COX2 Induction by IFNgamma and TNFalpha Self-Limits Type-1 Immunity in the Human Tumor Microenvironment. AB - Maintenance of CTL-, Th1-, and NK cell-mediated type-1 immunity is essential for effective antitumor responses. Unexpectedly, we observed that the critical soluble mediators of type-1 immune effector cells, IFNgamma and TNFalpha, synergize in the induction of cyclooxygenase 2 (COX2), the key enzyme in prostaglandin (PG)E2 synthesis, and the subsequent hyperactivation of myeloid derived suppressor cells (MDSC) within the tumor microenvironment (TME) of ovarian cancer patients. MDSC hyperactivation by type-1 immunity and the resultant overexpression of indoleamine 2,3-dioxygenase (IDO), inducible nitric oxide synthase (iNOS/NOS2), IL10, and additional COX2 result in strong feedback suppression of type-1 immune responses. This paradoxical immune suppression driven by type-1 immune cell activation was found to depend on the synergistic action of IFNgamma and TNFalpha, and could not be reproduced by either of these factors alone. Importantly, from a therapeutic standpoint, these negative feedback limiting type-1 responses could be eliminated by COX2 blockade, allowing amplification of type-1 immunity in the ovarian cancer TME. Our data demonstrate a new mechanism underlying the self-limiting nature of type-1 immunity in the human TME, driven by the synergistic induction of COX2 by IFNgamma and TNFalpha, and provide a rationale for targeting the COX2-PGE2 axis to enhance the effectiveness of cancer immunotherapies. PMID- 26817997 TI - Post-Sepsis State Induces Tumor-Associated Macrophage Accumulation through CXCR4/CXCL12 and Favors Tumor Progression in Mice. AB - Survivors from sepsis are in an immunosuppressed state that is associated with higher long-term mortality and risk of opportunistic infections. Whether these factors contribute to neoplastic proliferation, however, remains unclear. Tumor associated macrophages (TAM) can support malignant cell proliferation, survival, and angiogenesis. We addressed the relationship between the post-sepsis state, tumor progression and TAM accumulation, and phenotypic and genetic profile, using a mouse model of sepsis resolution and then B16 melanoma in mice. In addition, we measured the serum concentrations of TNFalpha, TGFbeta, CCL2, and CXCL12 and determined the effect of in vivo CXCR4/CXCL12 inhibition in this context. Mice that survived sepsis showed increased tumor progression both in the short and long term, and survival times were shorter. TAM accumulation, TAM local proliferation, and serum concentrations of TGFbeta, CXCL12, and TNFalpha were increased. Naive mice inoculated with B16 together with macrophages from post sepsis mice also had faster tumor progression and shorter survival. Post-sepsis TAMs had less expression of MHC-II and leukocyte activation-related genes. Inhibition of CXCR4/CXCL12 prevented the post-sepsis-induced tumor progression, TAM accumulation, and TAM in situ proliferation. Collectively, our data show that the post-sepsis state was associated with TAM accumulation through CXCR4/CXCL12, which contributed to B16 melanoma progression. PMID- 26817998 TI - Thymol accelerates the recovery of the skeletal muscle of mice injured with cardiotoxin. AB - OBJECTIVES: The aim of this study was to investigate the preventive effect of thymol in in vivo muscle inflammation and regeneration on cardiotoxin-induced injury. METHODS: Mice were pretreated (p.o.) with thymol (10-100 mg/kg), and after 1 h, cardiotoxin (25 MUM, 40 MUl) was administrated into the gastrocnemius muscle. The quantification of the areas of inflammation and regeneration of muscle tissue (3, 7 and 10 days) in HE-stained slides as well as the count of total mast cells and different phenotypes of mast cells were made. Sirius red staining was used to analyse total collagen expression. KEY FINDINGS: The pretreatment with thymol significantly reduced the area of inflammation (30 and 100 mg/kg) and increased the area of regeneration (100 mg/kg) 3 days after the cardiotoxin injection. Thymol at 30 and 100 mg/kg increased the area of collagen in 3 days and also decreased this area in 7 and 10 days, compared to the injured group. The pretreatment with thymol did not affect the number of total mast cells; however, it was able to change the number of mucosal mast cells within 10 days. CONCLUSIONS: This study suggests that thymol ameliorates inflammatory response and accelerates regeneration in cardiotoxin-induced muscle injury. PMID- 26817999 TI - Case Report: Next generation sequencing identifies a NAB2-STAT6 fusion in Glioblastoma. AB - BACKGROUND: Molecular profiling has uncovered genetic subtypes of glioblastoma (GBM), including tumors with IDH1 mutations that confer increase survival and improved response to standard-of-care therapies. By mapping the genetic landscape of brain tumors in routine clinical practice, we enable rapid identification of targetable genetic alterations. CASE PRESENTATION: A 29-year old male presented with new onset seizures prompting neuroimaging studies, which revealed an enhancing 5 cm intra-axial lesion involving the right parietal lobe. He underwent a subtotal resection and pathologic examination revealed glioblastoma with mitoses, microvascular proliferation and necrosis. Immunohistochemical (IHC) analysis showed diffuse expression of GFAP, OLIG2 and SOX2 consistent with a tumor of glial lineage. Tumor cells were positive for IDH1(R132H) and negative for ATRX. Clinical targeted-exome sequencing (DFBWCC Oncopanel) identified multiple functional variants including IDH1 (p.R132H), TP53 (p.Y126_splice), ATRX (p.R1302fs*), HNF1A (p.R263H) and NF1 (p.H2592del) variants and a NAB2-STAT6 gene fusion event involving NAB2 exon 3 and STAT6 exon 18. Array comparative genomic hybridization (aCGH) further revealed a focal amplification of NAB2 and STAT6. IHC analysis demonstrated strong heterogenous STAT6 nuclear localization (in 20 % of tumor cells). CONCLUSIONS: While NAB2:STAT6 fusions are common in solitary fibrous tumors (SFT), we report this event for the first time in a newly diagnosed, secondary-type GBM or any other non-SFT. Our study further highlights the value of comprehensive genomic analyses in identifying patient specific targetable mutations and rearrangements. PMID- 26818000 TI - Mechanisms of sex determination and transmission ratio distortion in Aedes aegypti. AB - BACKGROUND: More effective mosquito control strategies are urgently required due to the increasing prevalence of insecticide resistance. The sterile insect technique (SIT) and the release of insects carrying a dominant lethal allele (RIDL) are two proposed methods for environmentally-friendly, species-targeted population control. These methods may be more suitable for developing countries if producers reduce the cost of rearing insects. The cost of control programs could be reduced by producing all-male mosquito populations to circumvent the isolation of females before release without reducing male mating competitiveness caused by transgenes. RESULTS: An RNAi construct targeting the RNA recognition motif of the Aedes aegypti transformer-2 (tra-2) gene does not trigger female-to male sex conversion as commonly observed among dipterous insects. Instead, homozygous insects show greater mortality among m-chromosome-bearing sperm and mm zygotes, yielding up to 100% males in the subsequent generations. The performance of transgenic males was not significantly different to wild-type males in narrow cage competitive mating experiments. CONCLUSION: Our data provide preliminary evidence that the knockdown of Ae. aegypti tra-2 gene expression causes segregation distortion acting at the level of gametic function, which is reinforced by sex-specific zygotic lethality. This finding could promote the development of new synthetic sex distorter systems for the production of genetic sexing mosquito strains. PMID- 26818001 TI - Robustly photogenerating H2 in water using FeP/CdS catalyst under solar irradiation. AB - Photosplitting water for H2 production is a promising, sustainable approach for solar-to-chemical energy conversion. However, developing low-cost, high efficient and stable photocatalysts remains the major challenge. Here we report a composite photocatalyst consisting of FeP nanoparticles and CdS nanocrystals (FeP/CdS) for photogenerating H2 in aqueous lactic acid solution under visible light irradiation. Experimental results demonstrate that the photocatalyst is highly active with a H2-evolution rate of 202000 MUmol h(-1) g(-1) for the first 5 h (106000 MUmol h(-1) g(-1) under natural solar irradiation), which is the best H2 evolution activity, even 3-fold higher than the control in situ photo-deposited Pt/CdS system, and the corresponding to an apparent quantum efficiency of over 35% at 520 nm. More important, we found that the system exhibited excellent stability and remained effective after more than 100 h in optimal conditions under visible light irradiation. A wide-ranging analysis verified that FeP effectively separates the photoexcited charge from CdS and showed that the dual active sites in FeP enhance the activity of FeP/CdS photocatalysts. PMID- 26818002 TI - The occurrence of intracranial rhabdoid tumours in mice depends on temporal control of Smarcb1 inactivation. AB - Rhabdoid tumours (RTs) are highly aggressive tumours of infancy, frequently localized in the central nervous system (CNS) where they are termed atypical teratoid/rhabdoid tumours (AT/RTs) and characterized by bi-allelic inactivation of the SMARCB1 tumour suppressor gene. In this study, by temporal control of tamoxifen injection in Smarcb1(flox/flox);Rosa26-Cre(ERT2) mice, we explore the phenotypes associated with Smarcb1 inactivation at different developmental stages. Injection before E6, at birth or at 2 months of age recapitulates previously described phenotypes including embryonic lethality, hepatic toxicity or development of T-cell lymphomas, respectively. Injection between E6 and E10 leads to high penetrance tumours, mainly intra-cranial, with short delays (median: 3 months). These tumours demonstrate anatomical, morphological and gene expression profiles consistent with those of human AT/RTs. Moreover, intra- and inter-species comparisons of tumours reveal that human and mouse RTs can be split into different entities that may underline the variety of RT cells of origin. PMID- 26818004 TI - Follicular regulatory T cells can be specific for the immunizing antigen and derive from naive T cells. AB - T follicular regulatory (Tfr) cells are a subset of Foxp3(+) regulatory T (Treg) cells that form in response to immunization or infection, which localize to the germinal centre where they control the magnitude of the response. Despite an increased interest in the role of Tfr cells in humoral immunity, many fundamental aspects of their biology remain unknown, including whether they recognize self- or foreign antigen. Here we show that Tfr cells can be specific for the immunizing antigen, irrespective of whether it is a self- or foreign antigen. We show that, in addition to developing from thymic derived Treg cells, Tfr cells can also arise from Foxp3(-) precursors in a PD-L1-dependent manner, if the adjuvant used is one that supports T-cell plasticity. These findings have important implications for Tfr cell biology and for improving vaccine efficacy by formulating vaccines that modify the Tfr:Tfh cell ratio. PMID- 26818003 TI - Idelalisib for the treatment of non-Hodgkin lymphoma. AB - INTRODUCTION: B-cell Non-Hodgkin lymphomas (B-NHLs) include a number of disease subtypes, each defined by the tempo of disease progression and the identity of the cancerous cell. Idelalisib is a potent, selective inhibitor of the delta isoform of phosphatidylinositol-3-kinase (PI3K), a lipid kinase whose over activity in B-NHL drives disease progression. Idelalisib has demonstrated activity in indolent B-NHL (iB-NHL) and is approved for use as monotherapy in patients with follicular lymphoma and small lymphocytic lymphoma and in combination with rituximab in patients with chronic lymphocytic leukemia. AREAS COVERED: Herein we review the development and pharmacology of idelalisib, its safety and efficacy in clinical studies of iB-NHL, and its potential for inclusion in future applications in iB-NHL and in combination with other therapies. EXPERT OPINION: Idelalisib adds to the growing arsenal of iB-NHL pharmacotherapeutics and to the progression of the field toward precision agents with good efficacy and reduced toxicities. Nevertheless, idelalisib carries important risks that require careful patient counseling and monitoring. The appropriate sequencing of idelalisib with other proven treatment options in addition to its potential for combination with established or novel drugs will be borne out in ongoing and planned investigations. PMID- 26818005 TI - Trichomonas vaginalis infection and risk of advanced prostate cancer. AB - BACKGROUND: The epidemiologic evidence for an association of Trichomonas vaginalis (Tv) with overall prostate cancer is mixed, but some studies suggest Tv may increase risk of more aggressive disease. The aim of this study was to assess whether Tv serostatus is associated with advanced or fatal prostate cancer. METHODS: A total of 146 men with advanced (metastatic or fatal) prostate cancer and 181 age-matched controls were selected from two prior population-based, case control studies. Tv serostatus was determined with the same laboratory methods used in previous epidemiologic studies. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression to compare Tv serostatus in prostate cancer cases and controls adjusted for potential confounders. RESULTS: The seroprevalence of Tv in controls was 23%. Tv serostatus was not associated with an increased risk of metastatic or fatal prostate cancer (ORs < 1). CONCLUSIONS: Our study does not support an increased risk of advanced or fatal prostate cancer in men seropositive for Tv. PMID- 26818006 TI - Prediction of drugs having opposite effects on disease genes in a directed network. AB - BACKGROUND: Developing novel uses of approved drugs, called drug repositioning, can reduce costs and times in traditional drug development. Network-based approaches have presented promising results in this field. However, even though various types of interactions such as activation or inhibition exist in drug target interactions and molecular pathways, most of previous network-based studies disregarded this information. METHODS: We developed a novel computational method, Prediction of Drugs having Opposite effects on Disease genes (PDOD), for identifying drugs having opposite effects on altered states of disease genes. PDOD utilized drug-drug target interactions with 'effect type', an integrated directed molecular network with 'effect type' and 'effect direction', and disease genes with regulated states in disease patients. With this information, we proposed a scoring function to discover drugs likely to restore altered states of disease genes using the path from a drug to a disease through the drug-drug target interactions, shortest paths from drug targets to disease genes in molecular pathways, and disease gene-disease associations. RESULTS: We collected drug-drug target interactions, molecular pathways, and disease genes with their regulated states in the diseases. PDOD is applied to 898 drugs with known drug drug target interactions and nine diseases. We compared performance of PDOD for predicting known therapeutic drug-disease associations with the previous methods. PDOD outperformed other previous approaches which do not exploit directional information in molecular network. In addition, we provide a simple web service that researchers can submit genes of interest with their altered states and will obtain drugs seeming to have opposite effects on altered states of input genes at http://gto.kaist.ac.kr/pdod/index.php/main . CONCLUSIONS: Our results showed that 'effect type' and 'effect direction' information in the network based approaches can be utilized to identify drugs having opposite effects on diseases. Our study can offer a novel insight into the field of network-based drug repositioning. PMID- 26818007 TI - NMFP: a non-negative matrix factorization based preselection method to increase accuracy of identifying mRNA isoforms from RNA-seq data. AB - BACKGROUND: The advent of next-generation RNA sequencing (RNA-seq) has greatly advanced transcriptomic studies, including system-wide identification and quantification of mRNA isoforms under various biological conditions. A number of computational methods have been developed to systematically identify mRNA isoforms in a high-throughput manner from RNA-seq data. However, a common drawback of these methods is that their identified mRNA isoforms contain a high percentage of false positives, especially for genes with complex splicing structures, e.g., many exons and exon junctions. RESULTS: We have developed a preselection method called "Non-negative Matrix Factorization Preselection" (NMFP) which is designed to improve the accuracy of computational methods in identifying mRNA isoforms from RNA-seq data. We demonstrated through simulation and real data studies that NMFP can effectively shrink the search space of isoform candidates and increase the accuracy of two mainstream computational methods, Cufflinks and SLIDE, in their identification of mRNA isoforms. CONCLUSION: NMFP is a useful tool to preselect mRNA isoform candidates for downstream isoform discovery methods. It can greatly reduce the number of isoform candidates while maintaining a good coverage of unknown true isoforms. Adding NMFP as an upstream step, computational methods are expected to achieve better accuracy in identifying mRNA isoforms from RNA-seq data. PMID- 26818008 TI - Predicting transcription factor site occupancy using DNA sequence intrinsic and cell-type specific chromatin features. AB - BACKGROUND: Understanding the mechanisms by which transcription factors (TF) are recruited to their physiological target sites is crucial for understanding gene regulation. DNA sequence intrinsic features such as predicted binding affinity are often not very effective in predicting in vivo site occupancy and in any case could not explain cell-type specific binding events. Recent reports show that chromatin accessibility, nucleosome occupancy and specific histone post translational modifications greatly influence TF site occupancy in vivo. In this work, we use machine-learning methods to build predictive models and assess the relative importance of different sequence-intrinsic and chromatin features in the TF-to-target-site recruitment process. METHODS: Our study primarily relies on recent data published by the ENCODE consortium. Five dissimilar TFs assayed in multiple cell-types were selected as examples: CTCF, JunD, REST, GABP and USF2. We used two types of candidate target sites: (a) predicted sites obtained by scanning the whole genome with a position weight matrix, and (b) cell-type specific peak lists provided by ENCODE. Quantitative in vivo occupancy levels in different cell-types were based on ChIP-seq data for the corresponding TFs. In parallel, we computed a number of associated sequence-intrinsic and experimental features (histone modification, DNase I hypersensitivity, etc.) for each site. Machine learning algorithms were then used in a binary classification and regression framework to predict site occupancy and binding strength, for the purpose of assessing the relative importance of different contextual features. RESULTS: We observed striking differences in the feature importance rankings between the five factors tested. PWM-scores were amongst the most important features only for CTCF and REST but of little value for JunD and USF2. Chromatin accessibility and active histone marks are potent predictors for all factors except REST. Structural DNA parameters, repressive and gene body associated histone marks are generally of little or no predictive value. CONCLUSIONS: We define a general and extensible computational framework for analyzing the importance of various DNA-intrinsic and chromatin-associated features in determining cell-type specific TF binding to target sites. The application of our methodology to ENCODE data has led to new insights on transcription regulatory processes and may serve as example for future studies encompassing even larger datasets. PMID- 26818009 TI - Resourcing the clinical complementary medicine information needs of Australian medical students: Results of a grounded theory study. AB - The aim of this study was to identify Australian medical students' complementary medicine information needs. Thirty medical students from 10 medical education faculties across Australian universities were recruited. Data were generated using in-depth semi-structured interviews and constructivist grounded theory method was used to analyze and construct data. Students sought complementary medicine information from a range of inadequate sources, such as pharmacological texts, Internet searches, peer-reviewed medical journals, and drug databases. The students identified that many complementary medicine resources may not be regarded as objective, reliable, differentiated, or comprehensive, leaving much that medical education needs to address. Most students sought succinct, easily accessible, evidence-based information to inform safe and appropriate clinical decisions about complementary medicines. A number of preferred resources were identified that can be recommended and actively promoted to medical students. Therefore, specific, evidence-based complementary medicine databases and secondary resources should be subscribed and recommended to medical schools and students, to assist meeting professional responsibilities regarding complementary medicines. These findings may help inform the development of appropriate medical information resources regarding complementary medicines. PMID- 26818010 TI - Pathobiology of wound healing after glaucoma filtration surgery. AB - Conjunctival and subconjunctival fibrogenesis and inflammation are sight compromising side effects that can occur subsequent to glaucoma filtration surgery. Despite initial declines in intraocular pressure resulting from increasing aqueous outflow, one of the activated responses includes marshalling of proinflammatory and pro-fibrogenic cytokine mediator entrance into the aqueous through a sclerostomy window and their release by local cells, as well as infiltrating activated immune cells. These changes induce dysregulated inflammation, edema and extracellular matrix remodeling, which occlude outflow facility. A number of therapeutic approaches are being taken to offset declines in outflow facility since the current procedure of inhibiting fibrosis with either mitomycin C (MMC) or 5-fluorouracil (5-FU) injection is nonselective. One of them entails developing a new strategy for reducing fibrosis induced by wound healing responses including myofibroblast transdifferentiation and extracellular matrix remodeling in tissue surrounding surgically created shunts. The success of this endeavor is predicated on having a good understanding of conjunctival wound healing pathobiology. In this review, we discuss the roles of inappropriately activated growth factor and cytokine receptor linked signaling cascades inducing conjunctival fibrosis/scarring during post-glaucoma surgery wound healing. Such insight may identify drug targets for blocking fibrogenic signaling and excessive fibrosis which reduces rises in outflow facility resulting from glaucoma filtration surgery. PMID- 26818012 TI - Capsule Commentary on Calcaterra et al., Opioid Prescribing at Hospital Discharge Contributes to Chronic Opioid Use. PMID- 26818011 TI - Glycated Hemoglobin and Outcomes in Patients with Advanced Diabetic Chronic Kidney Disease. AB - Diabetes is the major risk factor for end-stage renal disease (ESRD) worldwide. In advanced chronic kidney disease (CKD), less is known about the predictive value of HbA1c. We enrolled 2401 diabetic patients with stage 3-4 and stage 5 CKD, who were classified into 4 groups according to their baseline HbA1c values (<6%, 6%-7%, 7%-9%, and >9%). During the median follow-up of 3 years, 895 patients developed ESRD, and 530 died. In linear regression analysis, higher HbA1c correlated with higher eGFR in patients with stage 5 CKD but not in stage 3 4 CKD. In Cox regression analysis, a trend toward worse clinical outcomes existed when the HbA1c level exceeded 6% in stage 3-4 CKD, but the significance was only observed for >9%. The hazard ratios (HRs) for ESRD, all-cause mortality and combined CV events with mortality in the group of HbA1c >9% were 1.6 (95% CI, 1.07 to 2.38), 1.52 (95% CI, 0.97 to 2.38) and 1.46 (95% CI, 1.02 to 2.09), respectively. This study demonstrates that the higher HbA1c level is associated higher risks for clinical outcomes in diabetic patients with stage 3-4 CKD but not in stage 5 CKD. PMID- 26818014 TI - Association between vitamin D and falls in young postmenopausal women. PMID- 26818013 TI - Sedentary lifestyle in middle-aged women is associated with severe menopausal symptoms and obesity. AB - OBJECTIVE: The aim of the study was to evaluate the association between sedentary lifestyle and the severity of menopausal symptoms and obesity in middle-aged women. METHODS: The Menopause Rating Scale, the Goldberg Anxiety and Depression Scale, and the Athens Insomnia Scale were administered to 6,079 Latin American women aged 40 to 59 years. Sedentary lifestyle was defined as fewer than three weekly, 30-minute periods of physical activity. RESULTS: Sedentary women had more severe menopausal symptoms (total Menopause Rating Scale score: 9.57 +/- 6.71 vs 8.01 +/- 6.27 points, P < 0.0001) and more depressive symptoms (Goldberg), anxiety (Goldberg), and insomnia (Athens Scale) compared with non-sedentary women. They also had greater mean waist circumference (86.2 +/- 12.3 vs 84.3 +/- 1.8 cm, P < 0.0001) and a higher prevalence of obesity (20.9% vs 14.3%, P < 0.0001). Logistic regression analysis showed that both obesity (odds ratio [OR] 1.52; 95% CI, 1.32-1.76) and severe menopausal symptoms (OR 1.28; 95% CI, 1.06 1.53), including insomnia and depressive mood, were positively associated with a sedentary lifestyle. Having a stable partner (OR 0.85; 95% CI, 0.76-0.96), using hormone therapy (OR 0.75; 95% CI, 0.64-0.87) and having a higher educational level (OR 0.66; 95% CI, 0.60-0.74) were negatively related to sedentary lifestyle. CONCLUSIONS: There was a high prevalence of sedentary lifestyle in this middle-aged Latin American female sample which was associated with more severe menopausal symptoms and obesity. PMID- 26818015 TI - Environmental assessment of the degradation potential of mushroom fruit bodies of Pleurotus ostreatus (Jacq.: Fr.) P. Kumm. towards synthetic azo dyes and contaminating effluents collected from textile industries in Karnataka, India. AB - Pleurotus ostreatus (Jacq.: Fr.) P. Kumm. is one of the edible mushrooms currently gaining attention as environmental restorer. The present study explores the potential of P. ostreatus (Jacq.: Fr.) P. Kumm. in degradation of textile dyes and effluents. The mushroom cultivation was carried out using paddy bed as substrate. The fully grown mushroom fruit bodies were used as a bioremediation agent against two industrially important azo dyes such as nylon blue and cotton yellow and few effluents collected from various textile industries in Karnataka, India. The ideal growth parameters such as temperature, pH, and dye concentrations for effective degradation were carried out. One of the main enzymes, laccase, responsible for biodegradation, was partially characterized. The degradation was found to be ideal at pH 3.0 and temperature at 26-28 degrees C. This study demonstrated a percentage degradation of 78.10, 90.81, 82.5, and 64.88 for dye samples such as nylon blue (50 ppm), cotton yellow (350 ppm), KSIC effluents, and Ramanagar effluents at 28 degrees C within 15th days respectively in comparison with other temperature conditions. Similarly, a percentage degradation of 35.99, 33.33, 76.13 and 25.8 for nylon blue (50 ppm), cotton yellow (350 ppm), Karnataka Silk Industries Corporation (KSIC) effluents and Ramnagar effluents were observed at pH 3.0 within 15 days, respectively (p < 0.05). Thus, the current study concluded that the utilization of P. ostreatus (Jacq.: Fr.) P. Kumm. at ideal environmental conditions is a cost-effective and eco-friendly approach for the degradation of various azo dyes and textile effluents which are harmful to the ecosystem. PMID- 26818016 TI - An assessment of non-volant terrestrial vertebrates response to wind farms--a study of small mammals. AB - The majority of studies on the effects of wind energy development on wildlife have been focused on birds and bats, whereas knowledge of the response of terrestrial, non-flying vertebrates is very scarce. In this paper, the impact of three functioning wind farms on terrestrial small mammal communities (rodents and shrews) and the population parameters of the most abundant species were studied. The study was carried out in southeastern Poland within the foothills of the Outer Western Carpathians. Small mammals were captured at 12 sites around wind turbines and at 12 control sites. In total, from 1200 trap-days, 885 individuals of 14 studied mammal species were captured. There was no difference in the characteristics of communities of small mammals near wind turbines and within control sites; i.e. these types of sites were inhabited by a similar number of species of similar abundance, similar species composition, species diversity (H' index) and species evenness (J') (Pielou's index). For the two species with the highest proportion in the communities (Apodemus agrarius and Microtus arvalis), the parameters of their populations (mean body mass, sex ratio, the proportion of adult individuals and the proportion of reproductive female) were analysed. In both species, none of the analysed parameters differed significantly between sites in the vicinity of turbines and control sites. For future studies on the impact of wind turbines on small terrestrial mammals in different geographical areas and different species communities, we recommend the method of paired 'turbine-control sites' as appropriate for animal species with pronounced fluctuations in population numbers. PMID- 26818017 TI - Distinct roles of hand2 in developing and adult autonomic neurons. AB - The bHLH transcription factor Hand2 is essential for the acquisition and maintenance of noradrenergic properties of embryonic sympathetic neurons and controls neuroblast proliferation. Hand2 is also expressed in embryonic and postnatal parasympathetic ganglia and remains expressed in sympathetic neurons up to the adult stage. Here, we address its function in developing parasympathetic and adult sympathetic neurons. We conditionally deleted Hand2 in the parasympathetic sphenopalatine ganglion by crossing a line of floxed Hand2 mice with DbhiCre transgenic mice, taking advantage of the transient Dbh expression in parasympathetic ganglia. Hand2 elimination does not affect Dbh expression and sphenopalatine ganglion size at E12.5 and E16.5, in contrast to sympathetic ganglia. These findings demonstrate different functions for Hand2 in the parasympathetic and sympathetic lineage. Our previous Hand2 knockdown in postmitotic, differentiated chick sympathetic neurons resulted in decreased expression of noradrenergic marker genes but it was unclear whether Hand2 is required for maintaining noradrenergic neuron identity in adult animals. We now show that Hand2 elimination in adult Dbh-expressing sympathetic neurons does not decrease the expression of Th and Dbh, in contrast to the situation during development. However, gene expression profiling of adult sympathetic neurons identified 75 Hand2-dependent target genes. Interestingly, a notable proportion of down-regulated genes (15%) encode for proteins with synaptic and neurotransmission functions. These results demonstrate a change in Hand2 target genes during maturation of sympathetic neurons. Whereas Hand2 controls genes regulating noradrenergic differentiation during development, Hand2 seems to be involved in the regulation of genes controlling neurotransmission in adult sympathetic neurons. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1111 1124, 2016. PMID- 26818018 TI - Cognitive and psychological functioning in focal dermal hypoplasia. AB - Focal dermal hypoplasia (FDH) is a condition caused by heterozygous mutation of the PORCN gene on chromosome Xp22.3. It impacts the primitive ectoderm and mesoderm, affecting skin, teeth, nails, hair, musculoskeletal development, and vision and hearing. To date, there has been no systematic research examining the psychoeducational impact of the disorder. The current study examined emotional, behavioral, adaptive, and intellectual ability in 17 subjects with ages ranging from 3 to 55 with FDH attending the 2013 Annual Family Conference of the National Foundation for Ectodermal Dysplasias. Findings suggested overall average functioning in all areas. However, wide variability was noted in this sample, with 3 participants (18%) exhibiting overall cognitive ability in the borderline to impaired range. These findings are consistent with previous reports suggesting intellectual impairment in 15% of persons with FDH. Similarly, a subgroup of children was rated by parents as exhibiting difficulties with behavior (2 out of 11; 18%) and emotions (5 out of 11; 45%). Of particular concern was withdrawn behavior, reported by 65% of parents. These findings suggest that clinicians should routinely screen persons with FDH to rule out cognitive and emotional/behavioral difficulties and offer timely treatment. Future research should focus on identifying risk factors for psychoeducational problems in this population. PMID- 26818019 TI - Age-related association of venom gene expression and diet of predatory gastropods. AB - BACKGROUND: Venomous organisms serve as wonderful systems to study the evolution and expression of genes that are directly associated with prey capture. To evaluate the relationship between venom gene expression and prey utilization, we examined these features among individuals of different ages of the venomous, worm eating marine snail Conus ebraeus. We determined expression levels of six genes that encode venom components, used a DNA-based approach to evaluate the identity of prey items, and compared patterns of venom gene expression and dietary specialization. RESULTS: C. ebraeus exhibits two major shifts in diet with age-an initial transition from a relatively broad dietary breadth to a narrower one and then a return to a broader diet. Venom gene expression patterns also change with growth. All six venom genes are up-regulated in small individuals, down-regulated in medium-sized individuals, and then either up-regulated or continued to be down regulated in members of the largest size class. Venom gene expression is not significantly different among individuals consuming different types of prey, but instead is coupled and slightly delayed with shifts in prey diversity. CONCLUSION: These results imply that changes in gene expression contribute to intraspecific variation of venom composition and that gene expression patterns respond to changes in the diversity of food resources during different growth stages. PMID- 26818020 TI - Comparison of the safety and efficacy of fixed-dose combination of arterolane maleate and piperaquine phosphate with chloroquine in acute, uncomplicated Plasmodium vivax malaria: a phase III, multicentric, open-label study. AB - BACKGROUND: Chloroquine has been the treatment of choice for acute vivax malaria for more than 60 years. Malaria caused by Plasmodium vivax has recently shown resistance to chloroquine in some places. This study compared the efficacy and safety of fixed dose combination (FDC) of arterolane maleate and piperaquine phosphate (PQP) with chloroquine in the treatment of uncomplicated vivax malaria. METHODS: Patients aged 13-65 years with confirmed mono-infection of P. vivax along with fever or fever in the previous 48 h were included. The 317 eligible patients were randomly assigned to receive FDC of arterolane maleate and PQP (n = 159) or chloroquine (n = 158) for 3 days. Primaquine was given as an anti-relapse measure on day 3 and continued for 14 consecutive days. Primary efficacy analysis included assessment of the proportion of aparasitaemic and afebrile patients at 72 h. Safety endpoints were analysis of adverse events, vital signs, laboratory data, and abnormalities on electrocardiograph. Patients participated in the study for at least 42 days. RESULTS: In per protocol population, the proportion of aparasitaemic and afebrile patients at 72 h was 100% (140/140) in the FDC of arterolane maleate and PQP group, and 99.3% (145/146) in the chloroquine group (Fisher, p > 0.9999). In intent to treat population, the corresponding value was reported to be 96.9% (154/159) in the FDC of arterolane maleate and PQP group and 98.7 % (156/158) in the chloroquine group (Fisher, p = 0.4479). The median parasite clearance time was 24 h in FDC of arterolane maleate and PQP group and 26 h in chloroquine group (Log-rank, p = 0.2264). Similarly, median fever clearance time was 24 h in both the groups (Log-rank, p = 0.7750). In PP population, day 28 cure rates were 100 % in both the groups (95% CI (96.52, 100.0 for FDC of arterolane maleate and PQP and 96.73, 100.0 in chloroquine group)). Incidence of adverse events was 82.4% in the FDC of arterolane maleate and PQP group and 85.4% in the chloroquine group. Most of the adverse events were mild to moderate in intensity. The commonly reported clinical adverse events in the FDC of arterolane maleate and PQP versus chloroquine group were vomiting (5.0 vs 5.1%), headache (1.3 vs 3.2%) and prolonged QT (1.9 vs 3.2%). No deaths were reported. The pharmacokinetic analysis indicates that arterolane maleate is well absorbed and has a relatively short t1/2 of 3.2 h. Piperaquine is also well absorbed after oral administration with a t1/2 of about 228.33 h. CONCLUSIONS: The study showed that FDC of arterolane maleate and PQP effectively cured vivax malaria and attained acceptable level of cure up to day 28. Both the groups showed similar safety profile. Trial Registration Clinical Trial Registry India: CTRI/2011/11/002129. PMID- 26818021 TI - Prostatic artery embolization for the treatment of symptomatic benign prostatic hyperplasia in men >=75 years: a prospective single-center study. AB - PURPOSE: To compare the safety and efficacy of PAE for the treatment of benign prostatic hyperplasia (BPH) in men >=75 years, who we defined as elderly, to those <75 years. METHODS: A total of 157 patients diagnosed with lower urinary tract symptoms (LUTS) due to BPH underwent PAE. Group A (n = 52) included patients >=75 years, and group B (n = 105) included patients <75 years. Follow-up was performed using the International Prostate Symptoms Score (IPSS), quality of life (QoL), peak urinary flow rate (Q max), post-void residual volume (PVR), the International Index of Erectile Function short form (IIEF-5), prostatic-specific antigen (PSA), and prostate volume (PV), at 1, 3, 6, and every 6 months thereafter. RESULTS: More coexistent systemic diseases were identified in group A than in group B (P < 0.05). Technical success rate of PAE was 90.4 % in group A and 95.2 % in group B (P = 0.06). A total of 147 patients had completed the follow-up with a mean of 20 months. Compared with the baseline, there were significant improvements in IPSS, QoL, Q max, PV, PVR, and PSA in both groups after PAE. There were no significant differences in the changes of IPSS, Q max, PVR, PSA, and IIEF-5 between groups after PAE. No major complications were noted. CONCLUSION: PAE could be used as an effective, safe, and well tolerable method in the treatment of elderly symptomatic BPH patients, similarly to younger patients, and it may play an important role in patients in whom medical therapy has failed, who are at high surgical and anesthetic risk or who refuse the standard surgical therapy. PMID- 26818022 TI - Editor's Choice - Subsequent Results for Arch Aneurysm Repair with Inner Branched Endografts. AB - OBJECTIVES: The aim was to evaluate the current results of aortic arch aneurysm repair using inner branched endografts performed in three high volume aortic endovascular centers and to compare them to the pioneering global experience with this technology. METHODS: Included patients underwent repair of aortic arch aneurysms >55 mm in diameter using inner branched endograft technology between April 2013 and November 2014. All patients were deemed unfit for open surgery. Inner branches were designed to perfuse the brachiocephalic trunk and the left common carotid artery in all cases. A left subclavian artery (LSA) revascularization was performed prior to the arch endovascular repair. Data were collected retrospectively in an electronic database. Parameters included length of procedure, fluoroscopy time, contrast volume, technical success, presence of endoleaks, early and late complications, and mortality. RESULTS: Twenty-seven patients were included in the study. Technical success was achieved in all cases. No patients died during the 30 day post-operative period. Early neurologic events included two major strokes (7.4%) and one minor stroke (3.7%). Transient spinal cord ischemia with full recovery was observed in two patients (7.4%). Four patients (14.8%) underwent early (<30 day) re-interventions; these were for an access complication, an ischemic limb and exploration of the left ventricle through a sternotomy in two patients. During follow up (median 12 months), one patient (3.7%) died from a remote thoraco-abdominal aneurysm rupture. There were three Type 2 endoleaks (11.1%). Two re-interventions (7.4%) were performed, one to treat a Type 2 endoleak and one to treat a septic false aneurysm. A significant decrease in overall mortality was observed when comparing patients from the early experience with patients from the current report. CONCLUSIONS: The early outcomes associated with this technology are favorable. Branched endografting of aortic arch aneurysms should be considered in patients unfit for open surgery. PMID- 26818023 TI - Commentary on 'Contrast Induced Nephropathy and Long-term Renal Decline After Percutaneous Transluminal Angioplasty for Symptomatic Peripheral Arterial Disease'. PMID- 26818024 TI - [Survey regarding the treatment of malignant middle cerebral artery infarction in German hospitals]. AB - BACKGROUND: There are a variety of intensive care therapies in the treatment of malignant middle cerebral artery infarction (MMI) besides hemicraniectomy (HC), the only treatment with proven efficacy. It is, however, not known how HC and conservative treatments are utilized in German hospitals, Furthermore, data on the care-situation of patients with MMI in Germany is scarce. METHODS: An anonymous questionnaire was sent to 297 neurological and 133 neurosurgical hospitals in Germany. RESULTS: The Response rate was 24,7%. Most respondents indicated personal experience in the treatment of MMI (83,3%). HC is usually performed early on site (83,3%). Indication to HC is confirmed on a high level of hierarchy and profession using clinical and radiological criteria in 78,2% of hospitals. Inherent standardized treatment protocols are established in 70,8% of hospitals. Patients are treated on an intensive care unit in 74,5% of hospitals after DHC and in 42,5% of hospitals under non-surgical treatment. Intracranial pressure monitoring is not performed on a regular basis. Differing opinions were observed concerning diagnosis and treatment of MMI without recognizable consensus. CONCLUSION: Basically, structural requirements for the treatment of MMI exist in the participating hospitals. Heterogeneity in the treatment of MMI is striking. The implementation of treatment protocols and adherence to guidelines are desirable steps to optimize treatment. PMID- 26818025 TI - Customized Tool for the Validation of Optical Coherence Tomography in Differentiation of Prostate Cancer. AB - OBJECTIVE: To design and demonstrate a customized tool to generate histologic sections of the prostate that directly correlate with needle-based optical coherence tomography pullback measurements. MATERIALS AND METHODS: A customized tool was created to hold the prostatectomy specimens during optical coherence tomography measurements and formalin fixation. Using the tool, the prostate could be sliced into slices of 4 mm thickness through the optical coherence tomography measurement trajectory. In this way, whole-mount pathology slides were produced in exactly the same location as the optical coherence tomography measurements were performed. Full 3-dimensional optical coherence tomography pullbacks were fused with the histopathology slides using the 3-dimensional imaging software AMIRA, and images were compared. RESULTS: A radical prostatectomy was performed in a patient (age: 68 years, prostate-specific antigen: 6.0 ng/mL) with Gleason score 3 + 4 = 7 in 2/5 biopsy cores on the left side (15%) and Gleason score 3 + 4 = 7 in 1/5 biopsy cores on the right side (5%). Histopathology after radical prostatectomy showed an anterior located pT2cNx adenocarcinoma (Gleason score 3 + 4 = 7). Histopathological prostate slides were produced using the customized tool for optical coherence tomography measurements, fixation, and slicing of the prostate specimens. These slides correlated exactly with the optical coherence tomography images. Various structures, for example, Gleason 3 + 4 prostate cancer, stroma, healthy glands, and cystic atrophy with septae, could be identified both on optical coherence tomography and on the histopathological prostate slides. CONCLUSION: We successfully designed and applied a customized tool to process radical prostatectomy specimens to improve the coregistration of whole mount histology sections to fresh tissue optical coherence tomography pullback measurements. This technique will be crucial in validating the results of optical coherence tomography imaging studies with histology and can easily be applied in other solid tissues as well, for example, lung, kidney, breast, and liver. This will help improve the efficacy of optical coherence tomography in cancer detection and staging in solid organs. PMID- 26818026 TI - GPU-Based Simulation of Ultrasound Imaging Artifacts for Cryosurgery Training. AB - This study presents an efficient computational technique for the simulation of ultrasound imaging artifacts associated with cryosurgery based on nonlinear ray tracing. This study is part of an ongoing effort to develop computerized training tools for cryosurgery, with prostate cryosurgery as a development model. The capability of performing virtual cryosurgical procedures on a variety of test cases is essential for effective surgical training. Simulated ultrasound imaging artifacts include reverberation and reflection of the cryoprobes in the unfrozen tissue, reflections caused by the freezing front, shadowing caused by the frozen region, and tissue property changes in repeated freeze-thaw cycles procedures. The simulated artifacts appear to preserve the key features observed in a clinical setting. This study displays an example of how training may benefit from toggling between the undisturbed ultrasound image, the simulated temperature field, the simulated imaging artifacts, and an augmented hybrid presentation of the temperature field superimposed on the ultrasound image. The proposed method is demonstrated on a graphic processing unit at 100 frames per second, on a mid range personal workstation, at two orders of magnitude faster than a typical cryoprocedure. This performance is based on computation with C++ accelerated massive parallelism and its interoperability with the DirectX-rendering application programming interface. PMID- 26818027 TI - Near-Infrared Spectroscopy and Imaging Studies of Fertilized Fish Eggs: In Vivo Monitoring of Egg Growth at the Molecular Level. AB - In this work, the growth of fertilized Japanese medaka (Oryzias latipes) eggs was monitored in vivo at the molecular level using near-infrared (NIR) spectroscopy and NIR imaging. NIR spectra were recorded noninvasively for three major parts of a fertilized medaka egg, the embryonic body, the oil droplets, and the yolk, from the first day after fertilization to the day before hatching. Principal component analysis (PCA) revealed that water, protein, and lipid contents in the egg yolk and oil droplets changed significantly just before hatching. The ratio of the characteristic peaks due to proteins and lipids in the second derivative spectra suggested that the relative concentration of proteins to lipids was constant in the egg yolk, while it dramatically increased just before hatching in the oil droplets. Furthermore, linear discriminant analysis (LDA) predicted the hatching possibility on the next day with 100% and 99.3% accuracy for yolk and oil droplets data, respectively. Two types of NIR images were developed in situ using the band intensities of the lipids and proteins in the second derivative spectra. The egg's protein and lipid content was successfully visualized noninvasively. This technique should enable noninvasive quality testing of fertilized eggs in the future. PMID- 26818028 TI - Preparation, characterization and in vitro release study of BSA-loaded double walled glucose-poly(lactide-co-glycolide) microspheres. AB - The aim of this study was to prepare a model protein, bovine serum albumin (BSA) loaded double-walled microspheres using a fast degrading glucose core, hydroxyl terminated poly(lactide-co-glycolide) (Glu-PLGA) and a moderate-degrading carboxyl-terminated PLGA polymers to reduce the initial burst release and to eliminate the lag phase from the release profile of PLGA microspheres. The double walled microspheres were prepared using a modified water-in-oil-in-oil-in-water (w/o/o/w) method and single-polymer microspheres were prepared using a conventional water-in-oil-in-water (w/o/w) emulsion solvent evaporation method. The particle size, morphology, encapsulation efficiency, thermal properties, in vitro drug release and structural integrity of BSA were evaluated in this study. Double-walled microspheres prepared with Glu-PLGA and PLGA polymers with a mass ratio of 1:1 were non-porous, smooth-surfaced, and spherical in shape. A significant reduction of initial burst release was achieved for the double-walled microspheres compared to single-polymer microspheres. In addition, microspheres prepared using Glu-PLGA and PLGA polymers in a mass ratio of 1:1 exhibited continuous BSA release after the small initial burst without any lag phase. It can be concluded that the double-walled microspheres made of Glu-PLGA and PLGA polymers in a mass ratio of 1:1 can be a potential delivery system for pharmaceutical proteins. PMID- 26818030 TI - A Year In Review In Minerva Anestesiologica 2015. Critical Care. Experimental and clinical studies. PMID- 26818029 TI - Prevalence, correlates, and associated psychological problems of substance use in Korean adolescents. AB - BACKGROUND: Substance use among Korean adolescents has been increasing, but little is known about the correlates of substance use in this population. Identification of the correlates is required for development of preventive approaches that aim to reduce or eliminate risk. Therefore, we examined the prevalence and correlates of substance use including psychological problems in a nationwide sample of Korean adolescents. METHODS: Data from the 2014 Korean Youth Risk Behavior Web-Based Survey, collected from 72,060 adolescents aged 12-18 years (mean age 14.94 +/- 1.75 years), were analyzed. Participants' lifetime experiences with substances (alcohol, tobacco, and illicit drugs) were assessed. Participants' perceived stress, depressive mood, and suicidality during the previous 12 months were also investigated. RESULTS: The lifetime prevalence estimates of alcohol, tobacco, and illicit drug use were 43.0, 19.9, and 0.4 % of the participants, respectively. The most commonly used illicit drugs were inhalants. Older age, male gender, non-residence with family, low parental educational level and socio-economic status, and low academic achievement were positively and significantly associated with substance use. Substance (alcohol, tobacco, and illicit drug) use was positively and significantly associated with severe stress, depressive mood, and suicidality during the previous 12 months, with the highest odds ratios obtained from illicit drug use. CONCLUSIONS: These results indicate that the use of substances (alcohol, tobacco, and illicit drugs) among Korean adolescents is associated with socially disadvantaged families, psychological problems, and risky behavior. Health education including dependency prevention programs is needed for these high-risk groups. PMID- 26818031 TI - Radiological analysis of upper lumbar disc herniation and spinopelvic sagittal alignment. AB - PURPOSE: A retrospective cross-sectional study was designed to explore the role of spinopelvic sagittal alignment in upper lumbar disc herniation (ULD) development. METHODS: A total of 207 consecutive patients who underwent surgery for single-level lumbar disc herniation [24 with ULD and 183 with lower lumbar disc herniation (LLD)] and 40 asymptomatic volunteers were enrolled. Full-length radiographs of the spine were taken to evaluate pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), thoracic kyphosis (TK), lumbar lordosis (LL), and sagittal vertical axis (SVA). The Roussouly classification was utilized to categorize all subjects according to their sagittal alignment. Spinopelvic parameters and Roussouly classification results were compared between groups. RESULTS: There were significant differences in PI, SS, PT, LL, and SVA between the ULD, LLD, and control groups. PI in the ULD (40.9 degrees ) was significantly lower than in the LLD and control groups (48.8 degrees and 47.6 degrees , respectively). LL was significantly lower in the ULD than in the LLD (-32.4 degrees and -40 degrees , respectively). There were significant differences between the three groups in Roussouly types. The LLD had a significantly higher proportion (62.6 %) of type 2 lordosis (flat back), and the ULD had a higher proportion (33.3 %) of type 1 lordosis than the other groups. CONCLUSIONS: This study demonstrated the importance of PI and lumbar curvature in the pathogenesis of ULD. The higher prevalence of short LL and long TK with low PI in the ULD group implies that an increased mechanical stress at this level may be one of the risk factors of ULD. PMID- 26818032 TI - Prospective study using anterior approach did not show association between Modic 1 changes and low grade infection in lumbar spine. AB - INTRODUCTION: The modern literature is producing a rapidly growing number of articles which highlight the relationship between infection and lumbar disc degeneration. However, the means by which samples are collected is questionable. Posterior approach surgery is not free from skin contamination. The possibility of intraoperative contamination of disc biopsies cannot be excluded. OBJECTIVE: The objective of this study was to determine if an association existed between lumbar disc degeneration and chronic infection of the intervertebral disc. MATERIALS AND METHODS: 313 patients (186/127, F/M) with chronic low back pain secondary to degenerative disc disease which was resistant to medical treatment were included in a single-centre prospective study. All underwent a lumbar anterior video-assisted minimally invasive fusion or disc prosthesis in L4-L5 and/or L5-S1 via an anterior retroperitoneal approach. The patients MRI scans demonstrated in Pfirrmann's classification grade IV or V disc degeneration; 385 disc drives were taken. In terms of Modic changes, 303 Modic 1, 58 Modic II and 24 absence of Modic change, respectively. All underwent intraoperative biopsy, performed according to a strict aseptic protocol. The biopsies were then cultured for 4 weeks with specialised enrichment cultures and subjected to histopathological analysis. RESULTS: The mean age was 47 +/- 8.6 years sterile cultures were obtained in 379 samples (98.4%) and 6 were positive (1.6%). The cultured bacteria were: Propionibacterium acnes (n:2), Staphylococcus epidermidis (n:2), Citrobacter freundii (n:1), and Saccharopolyspora hirsuta (n:1). Histopathological analysis did not demonstrate any evidence of a neutrophilia. There were no delayed or secondary infections. DISCUSSION AND CONCLUSION: Unlike the posterior approach where contamination is common, the anterior video-assisted approach allows a biopsy without skin contact. This approach to the spine is the most effective way to eliminate the risk of contamination. Our results confirm the absence of any relationship between infection and disc degeneration. We suggest that the 6 positive samples in our study may be related to contamination. The absence of infection at 1-year followup is an additional argument in favour of our results. In conclusion, our study shows no association between infection and disc degeneration. The pathophysiology of disc degeneration is complex, but the current literature opens new perspectives. PMID- 26818033 TI - Molecular characteristics and potential therapeutic targets in Merkel cell carcinoma. AB - Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin tumour occurring preferentially in elderly and immunosuppressed individuals. Multiple studies have provided insight into the molecular alterations of MCC, leading to the design of several ongoing clinical trials testing chemotherapy, targeted therapy and immunotherapy in patients with recurrent or metastatic disease. The results of some of these studies are available, whereas others are eagerly awaited and will likely shed light on the understanding of MCC biology and potentially improve the clinical outcomes of patients with this rare disease. PMID- 26818034 TI - Influence of clerks' personality on their burnout in the clinical workplace: a longitudinal observation. AB - BACKGROUND: The clinical training of medical students in clerkship is crucial to their future practice in healthcare services. This study investigates burnout during a 2-year clerkship training period as well as the role of personality traits on burnout during training. METHODS: Ninety-four clerks at a tertiary medical centre who provided at least 10 responses to a routine survey on clinical rotation were included in this study, which spanned September 2013 to April 2015. Web-based, validated, structured, self-administered questionnaires were used to evaluate the clerks' personalities at the beginning of the first clerkship year, and regular surveys were conducted to evaluate their burnout at each clinical specialty rotation throughout the 2-year clerkship period. Overall, 2230 responses were analysed, and linear mixed-effects models were used to examine the repeated measures of the clerks. RESULTS: Our findings revealed that medical student burnout scores were lower in the second year than they were in the first year of clerkships. Using the Big Five personality factors, all of the propensities, namely extroversion, agreeableness, consciousness, emotional stability, and openness were related to different extents of burnout reduction in the first clerkship year (P < .05). However, only emotional stability and openness were related to clerks' reduced burnout in the second clerkship year. Furthermore, being female, older, and with accompanied living were more closely related to lower burnout compared with being male, younger, and living alone throughout the clerkship period. CONCLUSIONS: The students in the first-year clerkship, particularly those with higher burnout levels, had tendencies in the Big Five personality characteristics, exhibiting higher levels of introversion, antagonism, lack of direction, neuroticism, and not open to new experiences. The students in the second-year clerkship who do not exhibit a high propensity for emotional stability and openness should be of particular concern. The findings can serve as a reference for clinical teachers and mentors to effectively prevent and reduce the burnout of medical students during clerkship training at clinical workplaces. PMID- 26818035 TI - Concurrent colonic mucosa-associated lymphoid tissue lymphoma and adenoma diagnosed after a positive fecal occult blood test: a case report. AB - BACKGROUND: Colonic lymphoma is an uncommon presentation of extranodal lymphoma. Colonic mucosa-associated lymphoid tissue lymphoma is a different entity from gastric mucosa-associated lymphoid tissue lymphoma, and very rare. The presentation and management of colonic mucosa-associated lymphoid tissue are highly variable in the literature. CASE PRESENTATION: We report the case of a 59 year-old Taiwanese man who underwent a colonoscopy after a positive test for fecal occult blood. His past history included hypertension and hyperthyroidism. The colonoscopy revealed an adenomatous polyp and mucosa-associated lymphoid tissue lymphoma. We successfully performed a polypectomy and endoscopic mucosal resection. The lymphoma was staged according to the Ann Arbor system modified by Musshoff as E-I. Our patient showed no lymphoma recurrence over a 3-year follow up. CONCLUSIONS: Endoscopic mucosal resection for colonic mucosa-associated lymphoid tissue lymphoma without disseminated disease may be feasible. We successfully used colonoscopic treatment without adjuvant therapy to treat early stage pathogen-free colonic mucosa-associated lymphoid tissue lymphoma. PMID- 26818037 TI - The BAC recommended code of practice for cytology laboratories participating in the UK cervical screening programmes 2015 - an introduction. PMID- 26818038 TI - BAC recommended code of practice for cytology laboratories participating in the UK cervical screening programmes 2015: a secondary publication. PMID- 26818039 TI - Attenuation of angiotensin type 2 receptor function in the rostral ventrolateral medullary pressor area of the spontaneously hypertensive rat. AB - We hypothesized that blockade of angiotensin II type 2 receptors (AT2Rs) in the rostral ventrolateral medullary pressor area (RVLM) may elicit sympathoexcitatory responses which are smaller in hypertensive rats compared to normotensive rats. This hypothesis was tested in urethane-anesthetized, artificially ventilated male 14-week-old spontaneously hypertensive rats (SHR). Age-matched male Wistar-Kyoto rats (WKY) and Wistar rats were used as controls. PD123319 (AT2R antagonist) was microinjected into the RVLM and mean arterial pressure (MAP), heart rate (HR) and greater splanchnic nerve activity (GSNA) were recorded. Increases in MAP, HR and GSNA elicited by unilateral microinjections of PD123319 into the RVLM were significantly smaller in SHR when compared with those in WKY and Wistar rats. Unilateral microinjections of l-glutamate (l-Glu) into the RVLM elicited greater increases in MAP and GSNA in SHR compared to those in WKY. AT2R immunoreactivity was demonstrated in the RVLM neurons which were retrogradely labeled from the intermediolateral cell column (IML) of the spinal cord. These results indicate that AT2Rs are present on the RVLM neurons projecting to the IML and their blockade results in sympathoexcitatory responses. Activation of AT2Rs has an inhibitory influence in the RVLM and these receptors are tonically active. Attenuation of the function of AT2Rs in the RVLM may play a role in genesis and/or maintenance of hypertension in SHR. PMID- 26818040 TI - Changes in Cognitive Processing Speed, Mood, and Fatigue in an Observational Study of Persons With Multiple Sclerosis Treated With Dalfampridine-ER. AB - OBJECTIVE: Multiple sclerosis (MS) is a degenerative neurological condition that results in impairments in multiple domains including cognition, fatigue, and mood. Dalfampridine-extended release (D-ER) has been approved to improve walking in persons with MS. It is plausible that D-ER could improve cognition, fatigue, and mood through the same mechanisms. We aim to examine effects of D-ER on cognition, depression, mood, and fatigue and to describe how these associations differ among those with and without D-ER related improvements in walking speed. METHODS: Patients with MS at the Mandell Center who were newly prescribed D-ER as part of their standard MS care were invited to participate in this observational pre-post study. Thirty-nine participants with MS were observed for 14 weeks; 31 remained on D-ER for 14 weeks or longer. Of these, 28 were then subdivided based on walk responder status. Cognition was assessed using the SDMT; depression was measured with the CESD. Self-reported cognition, mood, and fatigue were also measured using subscales of the Performance Scales (PS). RESULTS: Among those on drug through 14 weeks, there was significant improvement in the SDMT (P < 0.001) and the PS Fatigue score (P = 0.04). Among those who discontinued drug before 14 weeks, PS Cognition and PS Mood scores significantly improved (P = 0.02). Timed walk responders had significant improvements in SDMT (P < 0.001) and PS Fatigue (P = 0.046) from baseline to week 14. Among timed walk nonresponders, none of the measures significantly changed. CONCLUSIONS: Dalfampridine-extended release may improve cognition and fatigue in persons with MS, especially among timed walk responders. PMID- 26818041 TI - Development of Hiccup in Male Patients Hospitalized in a Psychiatric Ward: Is it Specifically Related to the Aripiprazole-Benzodiazepine Combination? AB - OBJECTIVES: The aim of this study was to identify hiccup cases among patients hospitalized in a psychiatric ward and focus on their treatment, so to establish intervention risk. METHODS: We reviewed records of 354 consecutively admitted patients during the year 2013 to identify hiccup cases. RESULTS: Hiccup occurred in 7 patients on both aripiprazole and benzodiazepines and in one on delorazepam. No patient on aripiprazole alone developed hiccup. No patient on drugs other than aripiprazole or benzodiazepines developed hiccup. The symptom subsided in 3 cases upon discontinuing aripiprazole and in 5 cases after discontinuing the benzodiazepine (including the case on delorazepam alone); in 2 cases of persistent hiccup, the symptom resolved after adding the calcium channel blocker, pregabalin. All patients developing hiccup were male. There was a 70-fold increase in the risk for developing hiccup in the aripiprazole/benzodiazepine intake condition versus all other conditions, and it further increased if limiting to the male sex. LIMITATIONS: The retrospective nature of the study was its limitation. CONCLUSIONS: Hospitalized psychiatric patients on both aripiprazole and benzodiazepines may be at significant risk of hiccup. This clinical awareness could lead to antipsychotic and/or benzodiazepine discontinuation or switch or to the addition of calcium channel blocker inhibitors. PMID- 26818042 TI - The Efficacy and Tolerability of Mycophenolate Mofetil in Treating Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorder in Western China. AB - OBJECTIVES: The aim of this study was to assess the efficacy and tolerability of mycophenolate mofetil (MMF) in neuromyelitis optica (NMO) or NMO spectrum disorder (NMOSD) in western China. METHODS: We enrolled 90 patients with NMO or NMOSD who had received MMF between January 1, 2010, and June 15, 2015. RESULTS: Of 90 patients, 62 (4 men and 58 women; aged 44.6 [11.5] years) were included in the study. After being treated for a median of 1.5 years (range, 0.5-4.1 years), the median annualized relapse rate for these 62 patients decreased from 1.2 (range, 0.2-7.0) pre-MMF to 0 (range, 0-1.7) post-MMF (P = 0.000), and the median Expanded Disability Status Scale score decreased from 4 (range, 0.5-8.0) pre-MMF to 2 (range, 0.5-7.5) post-MMF (P = 0.000). Thirty-six of the 62 patients were relapse free during MMF treatment. In the Cox regression, none of the following were identified as risk factors: disease duration, pre-MMF annualized relapse rate and Expanded Disability Status Scale, sex, concurrent use of prednisolone during MMF treatment, previous use of other immunosuppressive therapies (other than chronic prednisolone), and abnormal autoantibodies (other than NMO-IgG). However, serum NMO-IgG positivity (hazard ratio [HR], 11.408; 95% confidence interval [CI], 1.330-97.833; P = 0.026) and older age at onset (HR, 0.957; 95% CI, 0.917-0.999; P = 0.043) were significant risk factors. Kaplan-Meier survival analysis indicated a lower risk of relapse during MMF treatment relative to the pre-MMF period (HR, 0.439; 95% CI, 0.272-0.707; P = 0.001). None of the 62 patients discontinued MMF because of adverse effects. CONCLUSIONS: Mycophenolate mofetil is an effective and tolerable agent for reducing relapse and improving or stabilizing disabilities resulting from NMO or NMOSD. PMID- 26818043 TI - Clinical/Therapeutic Approaches for Cannabinoid Ligands in Central and Peripheral Nervous System Diseases: Mini Review. AB - OBJECTIVE: Cannabinoids, the components of Cannabis sativa Linnaeus, interact with CB1 and CB2 receptors, which are located both in the central nervous system and in the periphery and thus may exert a widespread biological activity in the body. The main medicinal properties of cannabinoids include analgesic, anti inflammatory, antitumor, appetite stimulation, antiemesis, and muscle relaxation effects. This mini review aims to explore existing clinical trials that investigated the use of cannabinoids in diseases affecting the nervous system. METHODS: We reviewed recent studies of cannabinoid-based therapy for disorders affecting central and peripheral nervous system in human subjects. RESULTS: There is evidence that cannabinoid-based drugs may effectively control some symptoms associated with nervous system dysfunction, especially various types of pain and neurologic disorders, although studies are limited. CONCLUSIONS: The efficacy of cannabinoid drugs in the treatment of nervous system diseases should be verified in future large-scale randomized clinical trials. PMID- 26818044 TI - Blonanserin Augmentation for Treatment-Resistant Somatic Symptom Disorder: A Case Series. AB - The augmentation of selective serotonin reuptake inhibitors with antipsychotics that have a high dopamine-receptor-D2 affinity may be effective in treatment resistant obsessive-compulsive disorder and somatic symptom disorder, which is similar to illness anxiety disorder. Blonanserin, a novel antipsychotic developed in Japan, has a high affinity for the D2 receptor and weak or very little affinity for other receptors. This article presents two case studies that demonstrate the efficacy of blonanserin augmentation for treatment-resistant somatic symptom disorder. Two patients with treatment-resistant somatic symptom disorder were prescribed concomitant use of blonanserin. Augmentation with blonanserin resulted in the remarkable amelioration of all symptoms. Sedative adverse drug reactions produced by aripiprazole were improved after replacing it with blonanserin. Blonanserin is effective in treatment-resistant somatic symptom disorder. Furthermore, compared with aripiprazole, blonanserin is more likely to result in medication adherence in patients with somatic symptom disorder because it reduced adverse drug reactions. PMID- 26818045 TI - Restless Leg Syndrome Induced by Escitalopram and Lithium Combined With Quetiapine Treatment in Bipolar II Disorder: A Case Report. PMID- 26818046 TI - Could Adult European Pharmacoresistant Epilepsy Patients Be Treated With Higher Doses of Zonisamide? AB - OBJECTIVE: To examine the clinical effect (efficacy and tolerability) of high doses of zonisamide (ZNS) (>500 mg/d) in adult patients with pharmacoresistant epilepsy. METHODS: Between 2006 and 2013, all epileptic outpatients treated with high doses of ZNS were selected. Safety and efficacy were assessed based on patient and caregiver reports. Serum levels of ZNS and other concomitant antiepileptic drugs were evaluated if available. RESULTS: Nine patients (5 female): 8 focal/1 generalized pharmacoresistant epilepsy. Mean age: 34 years. Most frequent seizure type: complex partial seizures; other seizure types: generalized tonic-clonic, tonic, myoclonia. Zonisamide in polytherapy in all (100%), administered in tritherapy in 3 (33%) of 9 patients; mean dose: 633 (600 700) mg/d; efficacy (>50% seizure reduction) was observed in 5 (55%) of 9 patients. Five of 9 patients are still taking high doses of ZNS (more than 1 year). Adverse events were observed in 3 (37%) of 8 patients. Good tolerance to high doses of other antiepileptic drugs had been observed in 6 (66%) of 9 patients. Plasma levels of ZNS were only available in 2 patients; both were in the therapeutic range (34.95, 30.91) (10-40 mg/L). CONCLUSIONS: High doses of ZNS are effective and safe in pharmacoresistant epileptic patients. Therapeutic drug monitoring of ZNS may be considered at therapeutic failure. PMID- 26818047 TI - Phenytoin-Induced Chorea: Drug Interaction or Genetic Predisposition? PMID- 26818048 TI - A Rare Case of Psychomotor Disturbances Linked to the Use of an Adulterated Dietary Supplement Containing Sibutramine. AB - BACKGROUND: Sibutramine, an oral anorexiant, is often found as an adulterant in various counterfeit herbal slimming products and dietary supplements. The use of sibutramine has been associated with various cardiovascular and psychiatric symptoms. Here, we report a rare case of psychomotor disturbances, in a patient with no previously diagnosed movement disorders. CASE: A 26-year-old woman developed abnormal behavior, visual hallucinations, hyperkinesia, facial flushing, and dizziness after taking a counterfeit dietary supplement which contained undeclared sibutramine and phenolphtalein. Laboratory work-up revealed microcytic anemia; leucopenia; and elevated erythrocyte sedimentation rate, C reactive protein levels, and antistreptolysin O titer, but rheumatic fever was ruled out. After a neurologic examination, involuntary movements were classified as chorea. The psychiatric examination result was unremarkable. The patient responded well to haloperidol therapy. Body temperature, erythrocyte sedimentation rate, and C-reactive protein levels eventually normalized. The patient was discharged. CONCLUSIONS: This is the first report we are aware of about a transient, chorea-like psychomotor movement disorder associated with sibutramine. Although the causal relationship between sibutramine and the patient's symptoms cannot be proven definitely, the temporal dimension does suggest sibutramine initiation and termination led to onset and resolution of symptoms, respectively. Furthermore, because of the widespread availability of adulterated food supplements containing sibutramine, physicians should be more aware of their implications for patients. PMID- 26818049 TI - Intermittent androgen deprivation in prostate cancer cases with biochemical progression after radical prostatectomy: Are we ready to treat? AB - PURPOSE: To evaluate clinical data from published trials on the use of intermittent androgen deprivation (IAD) therapy in patients with biochemical relapse after radical prostatectomy (RP). METHODS: We searched the Medline and Cochrane Library databases for literature published on IAD and biochemical progression after radical prostatectomy. RESULTS: To date, we have oncological and functional data from phase 3 studies focused on metastatic and locally advanced stages that confirmed IAD as a valid option treatment. For the aim of this review, only Tunn study, was specifically focused on patients who relapsed after surgery but clear and mature results are still missed. CONCLUSIONS: The use of IAD in cases who relapse after RP is common in the clinical practice. Although specific recommendation on the use of IAD in this setting of patients are not available, we concluded that the real benefit of IAD in terms of long survival and quality of life is mainly for patients treated with surgery. PMID- 26818050 TI - Thymoma and thymic carcinomas. AB - Thymomas (Ts) and thymic carcinomas (TCs) are rare tumours of the mediastinum with an incidence rate of 1.7/million per year in Europe. Histological classification is based on rate of non-malignant-appearing thymic epithelial cells and proportions of lymphocytes (A, AB, B1, B2, B3, and C), while staging system concerns localisation of the involved areas. Surgery is the mainstay of treatment with a 10-year survival of 80%, 78%, 75%, and 42% for stages I, II, III and IV, respectively, with an R0 resection. Radiotherapy has a role in selected cases (stage III patients or R1-2 residual) and platinum-based chemotherapy remains the standard of care for patients with advanced disease. A multimodality approach would be advisable when surgery is not recommended. Since molecular aberrations are poorly understood and few responses are reported, targeted therapies are yet being studied. In this review, we describe key aspects of clinical management for Ts and TCs. PMID- 26818051 TI - Is there still a role for sorafenib in metastatic renal cell carcinoma? A systematic review and meta-analysis of the effectiveness of sorafenib over other targeted agents. AB - BACKGROUND: The treatment of metastatic renal cell carcinoma (mRCC) has largely improved over the last decade, due to the availability of several targeted agents (TAs). Sorafenib was the first TA to report a benefit in terms of PFS in this disease, and it has largely been used as a comparator in randomized trials. We tested its activity compared to other TAs by performing a systematic review and meta-analysis. METHODS: MEDLINE/PubMed, the Cochrane library, and the ASCO university websites were searched for randomized phase II or III trials that compared other TAs to sorafenib in mRCC. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The measured outcomes were progression free survival (PFS), overall survival (OS), and the overall response rate (ORR). Sub-analyses were performed for MSKCC prognostic groups and lines of therapy. RESULTS: A total of 3094 patients were evaluable for PFS. Other TAs significantly reduce the risk of progression compared to sorafenib (HR=0.78; 95% CI, 0.72-0.85; p<0.001). This difference remains significant in patients in a good prognostic group with respect to both first- (HR=0.61; 95%CI, 0.44-0.85; p=0.003) and second-line therapy (HR=0.58; 95% CI, 0.42-0.79; p<0.001). No significant differences were, however, found in patients with an intermediate prognosis in terms of both first- (HR=0.80; 95% CI, 0.60-1.00; p=0.05) and second-line treatment (HR=0.89; 95% CI, 0.73-1.07; p=0.21). In 2922 patients evaluable for OS, no significant difference was found between other TAs and sorafenib (HR=1.07; 95% CI, 0.97-1.18; p=0.18). A benefit was also not identified when the analysis was limited to patients treated with first or subsequent lines of therapy or in patients previously treated with sunitinib. Significant differences were found in terms of the ORR in the 2963 evaluable patients favoring other TAs (RR=1.48; 95% CI, 1.24-1.76; p<0.001). This difference remain significant when a sub-analysis was performed per line of therapy. CONCLUSIONS: Other TAs improve PFS but not OS when compared to sorafenib. The use of sorafenib in patients with an intermediate prognosis, especially in second-line therapy, does not have a detrimental effect on PFS and might be an option for certain patients. PMID- 26818052 TI - Patients' views of adverse events in primary and ambulatory care: a systematic review to assess methods and the content of what patients consider to be adverse events. AB - BACKGROUND: Patient safety gained widespread public attention in the last 20 years. However, most patient safety research relied upon professionals' exceptions and was realised especially in the hospital sector. Gradually patients' attention has been focused on safety campaigns in inpatient care. We aimed to better assess patients' perceptions in primary and ambulatory care. METHODS: A systematic review was conducted by use of database searches with additional reference and hand searching. The search strategy implied MeSH-terms relating to adverse events, incident reporting and outpatient care. Relevant articles were selected by applying defined eligibility criteria. Studies exclusively based on hospital data as well as the professionals' point of view were excluded. RESULTS: We included 19 studies. Patients were able to identify events that were traditionally recognised by the medical community as technical medical aspects (e.g. errors in diagnosis). An important field of patient participation in prevention of adverse events was proposed in the medication process. Most reported events however could be described as service quality incidents. Communication problems were shown to have implications on the occurrence of technical medical aspects and patients' satisfaction of their care. Further, unsatisfied patients were more likely to recognize adverse events. CONCLUSION: Patients' perception of patient safety in primary and ambulatorycare broadened the previous focus on technical medical aspects. Especially communication factors played an important role in the occurrence and consequence of adverse events and patients' satisfaction. Future research should concentrate on developing possible ways to integrate patients' views and participation in ensuring safety in outpatient care. PMID- 26818053 TI - Ventilation changes associated with hatching and maturation of an endothermic phenotype in the Pekin duck, Anas platyrhynchos domestica. AB - Precocial birds begin embryonic life with an ectothermic metabolic phenotype and rapidly develop an endothermic phenotype after hatching. Switching to a high energy, endothermic phenotype requires high-functioning respiratory and cardiovascular systems to deliver sufficient environmental oxygen to the tissues. We measured tidal volume (VT), breathing frequency (f), minute ventilation (Ve), and whole-animal oxygen consumption (Vo2) in response to gradual cooling from 37.5 degrees C (externally pipped paranates, EP) or 35 degrees C (hatchlings) to 20 degrees C along with response to hypercapnia during developmental transition from an ectothermic, EP paranate to endothermic hatchling. To examine potential eggshell constraints on EP ventilation, we repeated these experiments in artificially hatched early and late EP paranates. Hatchlings and artificially hatched late EP paranates were able to increase Vo2significantly in response to cooling. EP paranates had high f that decreased with cooling, coupled with an unchanging low VT and did not respond to hypercapnia. Hatchlings had significantly lower f and higher VT and Ve that increased with cooling and hypercapnia. In response to artificial hatching, all ventilation values quickly reached those of hatchlings and responded to hypercapnia. The timing of artificial hatching influenced the temperature response, with only artificially hatched late EP animals, exhibiting the hatchling ventilation response to cooling. We suggest one potential constraint on ventilatory responses of EP paranates is the rigid eggshell, limiting air sac expansion during inhalation and constraining VT Upon natural or artificial hatching, the VT limitation is removed and the animal is able to increase VT, Ve, and thus Vo2, and exhibit an endothermic phenotype. PMID- 26818054 TI - Dietary fat and corticosterone levels are contributing factors to meal anticipation. AB - Daily restricted access to food leads to the development of food anticipatory activity and metabolism, which depends upon an as yet unidentified food entrainable oscillator(s). A premeal anticipatory peak in circulating hormones, including corticosterone is also elicited by daily restricted feeding. High-fat feeding is associated with elevated levels of corticosterone with disrupted circadian rhythms and a failure to develop robust meal anticipation. It is not clear whether the disrupted corticosterone rhythm, resulting from high-fat feeding contributes to attenuated meal anticipation in high-fat fed rats. Our aim was to better characterize meal anticipation in rats fed a low- or high-fat diet, and to better understand the role of corticosterone in this process. To this end, we utilized behavioral observations, hypothalamic c-Fos expression, and indirect calorimetry to assess meal entrainment. We also used the glucocorticoid receptor antagonist, RU486, to dissect out the role of corticosterone in meal anticipation in rats given daily access to a meal with different fat content. Restricted access to a low-fat diet led to robust meal anticipation, as well as entrainment of hypothalamic c-Fos expression, metabolism, and circulating corticosterone. These measures were significantly attenuated in response to a high-fat diet, and animals on this diet exhibited a postanticipatory rise in corticosterone. Interestingly, antagonism of glucocorticoid activity using RU486 attenuated meal anticipation in low-fat fed rats, but promoted meal anticipation in high-fat-fed rats. These findings suggest an important role for corticosterone in the regulation of meal anticipation in a manner dependent upon dietary fat content. PMID- 26818055 TI - Corticosterone administration in drinking water decreases high-fat diet intake but not preference in male rats. AB - One of the mechanisms through which regular exercise contributes to weight maintenance could be by reducing intake and preference for high-fat (HF) diets. Indeed, we previously demonstrated that wheel-running rats robustly reduced HF diet intake and preference. The reduced HF diet preference by wheel running can be so profound that the rats consumed only the chow diet and completely avoided the HF diet. Because previous research indicates that exercise activates the hypothalamic-pituitary-adrenal axis and increases circulating levels of corticosterone, this study tested the hypothesis that elevation of circulating corticosterone is involved in wheel running-induced reduction in HF diet preference in rats.Experiment 1 measured plasma corticosterone levels under sedentary and wheel-running conditions in the two-diet-choice (high-carbohydrate chow vs. HF) feeding regimen. The results revealed that plasma corticosterone is significantly increased and positively correlated with the levels of running in wheel-running rats with two-diet choice.Experiments 2 and 3 determined whether elevated corticosterone without wheel running is sufficient to reduce HF diet intake and preference. Corticosterone was elevated by adding it to the drinking water. Compared with controls, corticosterone-drinking rats had reduced HF diet intake and body weight, but the HF diet preference between groups did not differ. The results of this study support a role for elevated corticosterone on the reduced HF diet intake during wheel running. The elevation of corticosterone alone, however, is not sufficient to produce a robust reduction in HF diet preference. PMID- 26818056 TI - In vivo and in vitro degradation of peptide YY3-36 to inactive peptide YY3-34 in humans. AB - Peptide YY (PYY) is a 36-amino-acid peptide released from enteroendocrine cells upon food intake. The NH2 terminally truncated metabolite, PYY3-36, exerts anorexic effects and has received considerable attention as a possible antiobesity drug target. The kinetics and degradation products of PYY metabolism are not well described. A related peptide, neuropeptide Y, may be degraded from the COOH terminus, and in vivo studies in pigs revealed significant COOH-terminal degradation of PYY. We therefore investigated PYY metabolism in vitro after incubation in human blood and plasma and in vivo after infusion of PYY1-36 and PYY3-36 in eight young, healthy men. A metabolite, corresponding to PYY3-34, was formed after incubation in plasma and blood and during the infusion of PYY. PYY3 34 exhibited no agonistic or antagonistic effects on the Y2 receptor. PYY1-36 infused with and without coadministration of sitagliptin was eliminated with half lives of 10.1 +/- 0.5 and 9.4 +/- 0.8 min (means +/- SE) and metabolic clearance rates of 15.7 +/- 1.5 and 14.1 +/- 1.1 ml.kg(-1).min(-1) after infusion, whereas PYY3-36 was eliminated with a significantly longer half-life of 14.9 +/- 1.3 min and a metabolic clearance rate of 9.4 +/- 0.6 ml.kg(-1).min(-1) We conclude that, upon intravenous infusion in healthy men, PYY is inactivated by cleavage of the two COOH-terminal amino acids. In healthy men, PYY3-36 has a longer half-life than PYY1-36. PMID- 26818057 TI - Thalamic mediation of hypoxic respiratory depression in lambs. AB - Immaturity of respiratory controllers in preterm infants dispose to recurrent apnea and oxygen deprivation. Accompanying reductions in brain oxygen tensions evoke respiratory depression, potentially exacerbating hypoxemia. Central respiratory depression during moderate hypoxia is revealed in the ventilatory decline following initial augmentation. This study determined whether the thalamic parafascicular nuclear (Pf) complex involved in adult nociception and sensorimotor regulation (Bentivoglio M, Balerecia G, Kruger L. Prog Brain Res 87: 53-80, 1991) also becomes a postnatal controller of hypoxic ventilatory decline. Respiratory responses to moderate isocapnic hypoxia were studied in conscious lambs. Hypoxic ventilatory decline was compared with peak augmentation. Pf and/or adjacent thalamic structures were destroyed by the neuron-specific toxin ibotenic acid (IB). IB lesions involving the thalamic Pf abolished hypoxic ventilatory decline. Lesions of adjacent thalamic nuclei that spared Pf and control injections of vehicle failed to blunt hypoxic respiratory depression. Our findings reveal that the thalamic Pf region is a critical controller of hypoxic ventilatory depression and thus a key target for exploring molecular concomitants of forebrain pathways regulating hypoxic ventilatory depression in early development. PMID- 26818058 TI - Characterization of bladder and external urethral activity in mice with or without spinal cord injury--a comparison study with rats. AB - To clarify the lower urinary tract function in mice, we compared bladder and urethral activity between rats and mice with or without spinal cord injury (SCI). Female Sprague-Dawley rats and C57BL/6N mice were divided into five groups:1) spinal intact (SI) rats,2) SI mice,3) pudendal nerve transection (PNT) SI mice,4) spinal cord injury (SCI) rats, and 5) SCI mice. Continuous cystometry (CMG) and external urethral sphincter (EUS)-electromyogram (EMG) analyses were conducted under an awake, restrained condition. During voiding bladder contractions, SI animals exhibited EUS bursting with alternating active and silent periods, which, in rats but not mice, coincided with small-amplitude intravesical pressure oscillations in CMG recordings. In SI mice with bursting-like EUS activity, the duration of active periods was significantly shorter by 46% (32 +/- 5 ms) compared with SI rats (59 +/- 9 ms). In PNT-SI mice, there were no significant differences in any of cystometric parameters compared with SI mice. In SCI rats, fluid elimination from the urethra and the EUS bursting occurred during small amplitude intravesical pressure oscillations. However, SCI mice did not exhibit clear EUS bursting activity or intravesical pressure oscillations but rather exhibited intermittent voiding with slow large-amplitude reductions in intravesical pressure, which occurred during periods of reduced EUS activity. These results indicate that EUS pumping activity is essential for generating efficient voiding in rats with or without spinal cord injury. However, EUS bursting activity is not required for efficient voiding in SI mice and does not reemerge in SCI mice in which inefficient voiding occurs during periods of reduced tonic EUS activity. PMID- 26818059 TI - Positive airway pressure improves nocturnal beat-to-beat blood pressure surges in obesity hypoventilation syndrome with obstructive sleep apnea. AB - Positive airway pressure (PAP) treatment has been shown to have a modest effect on ambulatory blood pressure (BP) in patients with obstructive sleep apnea (OSA). However, there is a paucity of data on the effect of PAP therapy on rapid, yet significant, BP swings during sleep, particularly in obesity hypoventilation syndrome (OHS). The present study hypothesizes that PAP therapy will improve nocturnal BP on the first treatment night (titration PAP) in OHS patients with underlying OSA, and that these improvements will become more significant with 6 wk of PAP therapy. Seventeen adults (7 men, 10 women; age 50.4 +/- 10.7 years, BMI 49.3 +/- 2.4 kg/m(2)) with OHS and clinically diagnosed OSA participated in three overnight laboratory visits that included polysomnography and beat-to-beat BP monitoring via finger plethysmography. Six weeks of PAP therapy, but not titration PAP, lowered mean nocturnal BP. In contrast, when nocturnal beat-to beat BPs were aggregated into bins consisting of at least three consecutive cardiac cycles with a >10 mmHg BP surge (i.e., Delta10-20, Delta20-30, Delta30 40, and Delta>40 mmHg), titration, and 6-wk PAP reduced the number of BP surges per hour (time * bin, P < 0.05). PAP adherence over the 6-wk period was significantly correlated to reductions in nocturnal systolic (r = 0.713, P = 0.001) and diastolic (r = 0.497, P = 0.043) BP surges. Despite these PAP-induced improvements in nocturnal beat-to-beat BP surges, 6 wk of PAP therapy did not alter daytime BP. In conclusion, PAP treatment reduces nocturnal beat-to-beat BP surges in OHS patients with underlying OSA, and this improvement in nocturnal BP regulation was greater in patients with higher PAP adherence. PMID- 26818062 TI - Social Anxiety and Quality of Life in Vitiligo and Acne Patients with Facial Involvement: A Cross-Sectional Controlled Study. AB - BACKGROUND: Vitiligo and acne vulgaris, commonly affecting the face, have significant psychological effects and impair the quality of life of the affected individuals. Because of their negative effect on physical appearance, these conditions may act as a potential barrier to social relationships and cause social anxiety. OBJECTIVE: The objective of the study was to investigate the social anxiety, quality of life, anxiety, and depression levels of acne and vitiligo patients with facial involvement and compare these levels with healthy controls. METHODS: Thirty-seven vitiligo and 37 acne patients, aged older than 18 years, with facial involvement and 74 age- and sex-matched healthy control subjects were included in the study. The patients and healthy controls were asked to complete the Liebowitz Social Anxiety Scale, the Hospital Anxiety and Depression Scale, and the Dermatology Life Quality Index. Disease severity was evaluated both objectively by the physician and subjectively by the patients using a visual analog scale. RESULTS: Social anxiety, depression, and anxiety levels of vitiligo and acne patients were significantly higher than healthy controls (p < 0.05). Quality of life was impaired in both patient groups (Dermatology Life Quality Index scores for vitiligo: 5.6 +/- 5.1; acne: 6.4 +/- 6.2). There was no correlation between psychiatric scale scores and disease severity. Quality of life was negatively correlated with social anxiety and depression levels in both patient groups in our study. CONCLUSION: Vitiligo and acne patients had higher levels of social anxiety, anxiety, and depression compared with healthy control subjects. Considering that increased psychosocial morbidity was regardless of age, sex, and disease severity and was correlated with quality of life impairment, evaluation of the psychosocial morbidity, in particular social anxiety, may be valuable in all vitiligo and acne patients. PMID- 26818060 TI - Endothelin therapeutics in cancer: Where are we? AB - In human cancers, the autocrine and paracrine loop mediated by the aberrantly activation of endothelin-1 (ET-1) receptor (ET-1R) elicits pleiotropic effects, preferentially mediated by the scaffold protein beta-arrestin 1 (beta-arr1), on tumor cells and on the host microenvironment, providing a strong rationale for targeting ET-1 receptors. This review describes the most up-to-date preclinical and clinical results obtained by using ET-1 therapeutics. The previous negative clinical results of ET-1 therapeutics should not prevent us from setting the standard of this class of drugs for future well-designed clinical trials. The preclinical data obtained with the dual ETAR and ETBR antagonist macitentan indicate that this molecule, which targets cancer cells and tumor-associated microenvironmental elements, could be a cancer therapeutic option. The field of ET-1 therapeutics will be improved in the next decade, facilitated by the new knowledge on the genomic landscape of the human stroma and tumor, and by the low invasive approaches based on liquid biopsies for the discovery of predictive biomarkers. The information obtained from preclinical studies in patient-derived models and from the Cancer Genome Atlas will set the scene of precision medicine for cancer. Results from these studies are expected to open the possibility that ET-1R antagonists might be more efficacious as molecular cancer therapeutics, able to hamper the functional beta-arr1-dependent signaling complexes, either alone or coupled with new targeted approaches. PMID- 26818063 TI - Quality of Life in Patients with Atopic Dermatitis: Disease Burden, Measurement, and Treatment Benefit. AB - Health-related quality of life (HRQoL) is often markedly impaired in both adults and children with atopic dermatitis. The quality of life of the parents of infants or children with this chronic disease is also affected owing to problems such as itch-induced sleeping problems and treatment effort. As HRQoL is only partly associated with disease severity, both parameters should be evaluated in research and clinical practice. For the measurement of HRQoL, both skin- and disease-specific questionnaires are available in addition to generic instruments. In randomized controlled trials on atopic dermatitis, HRQoL is most commonly evaluated with the Dermatology Life Quality Index for use in adults and related questionnaires for children and families, such as the Children's Dermatology Life Quality Index. There is evidence that different treatment modalities may be effective in improving HRQoL in adults, children, and parents, which is supported by the patients' own evaluation of treatment benefit in an observational study. PMID- 26818064 TI - The place of viscoelastic testing in clinical practice. AB - Hellmut Hartert was the first person to exploit the viscoelastic properties of clotting blood to measure blood coagulation in 1948. Since then, the technology has improved, allowing these analyses to be performed as point-of-care tests with immediately-available results. The addition of several activators and inhibitors to the original assay creates a panel of tests able to quantify the different aspects of blood clotting that can rival conventional laboratory assays. However, although much progress has been made, the standardization and validation of these tests still need improvement. Viscoelastic analyses of blood coagulation are mainly used to guide haemostatic therapy in bleeding patients and have proven superior to standard clotting tests in some circumstances. There is potential to extend their use to other areas, such as drug monitoring, and diagnosis and management of congenital bleeding disorders. The forthcoming cartridge-based assays are expected to improve the reliability and usability of viscoelastic assays of blood coagulation but high quality clinical trials remain urgently needed to determine their exact place, benefit and cost effectiveness. PMID- 26818065 TI - Longitudinal study of psychopathological, anthropometric and sociodemographic factors related to the level of Mediterranean diet adherence in a community sample of Spanish adolescents. AB - OBJECTIVE: The Mediterranean diet (MD) pattern has important health benefits; however, it seems that Spanish school-aged children have been abandoning this healthy pattern recently. We aimed to identify psychopathological, anthropometric and sociodemographic factors that may influence the risk of low MD adherence. DESIGN: Longitudinal study in three phases. MD adherence was assessed using the Krece Plus food questionnaire and psychopathological symptoms using the Screen for Childhood Anxiety Related Emotional Disorders, Children's Depression Inventory, Youth's Inventory-4 and Eating Disorder Inventory-2. Anthropometric data were collected in the first and third phases. Settings All five representative areas in Reus, Spain. SUBJECTS: Adolescents (n 241). RESULTS: Regardless of past and current BMI, socio-economic status was a protective factor for low MD adherence (OR=0.805, P=0.003) and a risk factor for high BMI (OR=0.718, P=0.002; OR=0.707, P=0.001). Regardless of socio-economic status, depression was involved with risk of low adherence (OR=1.069, P=0.021). Girls with lower MD adherence presented significantly higher scores for eating disorders measured using the Eating Disorder Inventory-2 (low adherence, mean 18.9 (sd 13.5); high adherence, mean 8.9 (sd 9.0), P=0.020) and the Youth Inventory-4 (low adherence, mean 5.2 (sd 4.3); medium adherence, mean 3.6 (sd 3.2), P=0.044). They also presented higher depression symptoms (low adherence, mean 17.7 (sd 9.6); medium adherence, mean 12.3 (sd 7.2), P=0.01) than girls with high adherence. CONCLUSIONS: The results highlight the influence of psychosocial factors on levels of MD adherence. These factors need to be taken into account when developing prevention and health promotion initiatives. PMID- 26818066 TI - Selected analytical challenges in the determination of pharmaceuticals in drinking/marine waters and soil/sediment samples. AB - Recent developments and improvements in advanced instruments and analytical methodologies have made the detection of pharmaceuticals at low concentration levels in different environmental matrices possible. As a result of these advances, over the last 15 years residues of these compounds and their metabolites have been detected in different environmental compartments and pharmaceuticals have now become recognized as so-called 'emerging' contaminants. To date, a lot of papers have been published presenting the development of analytical methodologies for the determination of pharmaceuticals in aqueous and solid environmental samples. Many papers have also been published on the application of the new methodologies, mainly to the assessment of the environmental fate of pharmaceuticals. Although impressive improvements have undoubtedly been made, in order to fully understand the behavior of these chemicals in the environment, there are still numerous methodological challenges to be overcome. The aim of this paper therefore, is to present a review of selected recent improvements and challenges in the determination of pharmaceuticals in environmental samples. Special attention has been paid to the strategies used and the current challenges (also in terms of Green Analytical Chemistry) that exist in the analysis of these chemicals in soils, marine environments and drinking waters. There is a particular focus on the applicability of modern sorbents such as carbon nanotubes (CNTs) in sample preparation techniques, to overcome some of the problems that exist in the analysis of pharmaceuticals in different environmental samples. PMID- 26818067 TI - Four sessions of spinal manipulation, simple exercises and education are not better than usual care for patients with acute low back pain. PMID- 26818068 TI - Mailing free nicotine patches to smokers reduces smoking rates, study shows. PMID- 26818069 TI - ICAT: a simple score predicting critical care needs after thrombolysis in stroke patients. AB - BACKGROUND: Patients receiving intravenous thrombolysis (IVT) for acute ischemic stroke are at risk of developing complications, commonly necessitating admission to an intensive care unit (ICU). At present, most IVT is administered in the Emergency Department or in dedicated stroke units, but no evidence-based criteria exist that allow for early identification of patients at increased risk of developing ICU needs. The present study describes a novel prediction score aiming to identify a subpopulation of post-IVT patients at high risk for critical care interventions. METHODS: We retrospectively analyzed data from 301 patients undergoing IVT at our institutions during a 5-year period. Two hundred and ninety patients met inclusion criteria. The sample was randomly divided into a development and a validation cohort. Logistic regression was used to develop a risk score by weighting predictors of critical care needs based on strength of association. RESULTS: Seventy-two patients (24.8%) required critical care interventions. Black race (odds ratio [OR] 3.81, p=0.006), male sex (OR 3.79, p=0.008), systolic blood pressure (SBP; OR 1.45 per 10 mm Hg increase in SBP, p<0.001), and NIH stroke scale (NIHSS; OR 1.09 per 1 point increase in NIHSS, p=0.071) were independent predictors of critical care needs. The optimal model for score development, predicting critical care needs, achieved an AUC of 0.782 in the validation group. The score was named the ICAT (Intensive Care After Thrombolysis) score, assigning the following points: black race (1 point), male sex (1 point), SBP (2 points if 160-200 mm Hg; 4 points if >200 mm Hg), and NIHSS (1 point if 7-12; 2 points if >12). Each 1-point increase in the score was associated with 2.22-fold increased odds for critical care needs (95% CI 1.78 2.76, p<0.001). A score >= 2 was associated with over 13 times higher odds of critical care needs compared to a score <2 (OR 13.60, 95% CI 3.23-57.19), predicting critical care with 97.2% sensitivity and 28.0% specificity. CONCLUSION: The ICAT score, combining information about race, sex, SBP, and NIHSS, predicts critical care needs in post-IVT patients and may be helpful when triaging post-IVT patients to the appropriate monitoring environment. PMID- 26818070 TI - A Reliable Hybrid Adsorbent for Efficient Radioactive Cesium Accumulation from Contaminated Wastewater. AB - Cesium (Cs) removal from nuclear liquid wastewater has become an emerging issue for safeguarding public health after the accident at the Fukushima Daiichi Nuclear Power Plant. A novel macrocyclic ligand of o-benzo-p-xylyl-22-crown-6 ether (OBPX22C6) was developed and successfully immobilized onto mesoporous silica for the preparation of hybrid adsorbent. The benzene ring pi electron is the part of crown ether of OBPX22C6 for easy orientation of the macrocyclic compound for making the pi electron donation with Cs complexation. The potential and feasibility of the hybrid adsorbent as being Cs selective was evaluated in terms of sensitivity, selectivity and reusability. The results clarified that the Cs removal process was rapid and reached saturation within a short time. Considering the effect of competitive ions, sodium (Na) did not markedly affect the Cs adsorption whereas potassium (K) was slightly affected due to the similar ionic radii. However, the oxygen in long ethylene glycol chain in OBPX22C6 was expected to show strong coordination, including Cs-pi interaction with Cs even in the presence of the high amount of K and Na. Due to its high selectivity and reusability, significant volume reduction is expected as this promising hybrid adsorbent is used for Cs removal in Fukushima wastewater. PMID- 26818071 TI - Drak Is Required for Actomyosin Organization During Drosophila Cellularization. AB - The generation of force by actomyosin contraction is critical for a variety of cellular and developmental processes. Nonmuscle myosin II is the motor that drives actomyosin contraction, and its activity is largely regulated by phosphorylation of the myosin regulatory light chain. During the formation of the Drosophila cellular blastoderm, actomyosin contraction drives constriction of microfilament rings, modified cytokinesis rings. Here, we find that Drak is necessary for most of the phosphorylation of the myosin regulatory light chain during cellularization. We show that Drak is required for organization of myosin II within the microfilament rings. Proper actomyosin contraction of the microfilament rings during cellularization also requires Drak activity. Constitutive activation of myosin regulatory light chain bypasses the requirement for Drak, suggesting that actomyosin organization and contraction are mediated through Drak's regulation of myosin activity. Drak is also involved in the maintenance of furrow canal structure and lateral plasma membrane integrity during cellularization. Together, our observations suggest that Drak is the primary regulator of actomyosin dynamics during cellularization. PMID- 26818072 TI - A Plasmid Set for Efficient Bacterial Artificial Chromosome (BAC) Transgenesis in Zebrafish. AB - Transgenesis of large DNA constructs is essential for gene function analysis. Recently, Tol2 transposase-mediated transgenesis has emerged as a powerful tool to insert bacterial artificial chromosome (BAC) DNA constructs into the genome of zebrafish. For efficient transgenesis, the genomic DNA piece in the BAC construct needs to be flanked by Tol2 transposon sites, and the constructs should contain a transgenesis marker for easy identification of transgenic animals. We report a set of plasmids that contain targeting cassettes that allow the insertion of Tol2 sites and different transgenesis markers into BACs. Using BACs containing these targeting cassettes, we show that transgenesis is as efficient as iTol2, that preselecting for expression of the transgenesis marker increases the transgenesis rate, and that BAC transgenics faithfully recapitulate the endogenous gene expression patterns and allow for the estimation of the endogenous gene expression levels. PMID- 26818073 TI - Haplotag: Software for Haplotype-Based Genotyping-by-Sequencing Analysis. AB - Genotyping-by-sequencing (GBS), and related methods, are based on high-throughput short-read sequencing of genomic complexity reductions followed by discovery of single nucleotide polymorphisms (SNPs) within sequence tags. This provides a powerful and economical approach to whole-genome genotyping, facilitating applications in genomics, diversity analysis, and molecular breeding. However, due to the complexity of analyzing large data sets, applications of GBS may require substantial time, expertise, and computational resources. Haplotag, the novel GBS software described here, is freely available, and operates with minimal user-investment on widely available computer platforms. Haplotag is unique in fulfilling the following set of criteria: (1) operates without a reference genome; (2) can be used in a polyploid species; (3) provides a discovery mode, and a production mode; (4) discovers polymorphisms based on a model of tag-level haplotypes within sequenced tags; (5) reports SNPs as well as haplotype-based genotypes; and (6) provides an intuitive visual "passport" for each inferred locus. Haplotag is optimized for use in a self-pollinating plant species. PMID- 26818074 TI - Aberrant Activation of p38 MAP Kinase-Dependent Innate Immune Responses Is Toxic to Caenorhabditis elegans. AB - Inappropriate activation of innate immune responses in intestinal epithelial cells underlies the pathophysiology of inflammatory disorders of the intestine. Here we examine the physiological effects of immune hyperactivation in the intestine of the nematode Caenorhabditis elegans. We previously identified an immunostimulatory xenobiotic that protects C. elegans from bacterial infection by inducing immune effector expression via the conserved p38 MAP kinase pathway, but was toxic to nematodes developing in the absence of pathogen. To investigate a possible connection between the toxicity and immunostimulatory properties of this xenobiotic, we conducted a forward genetic screen for C. elegans mutants that are resistant to the deleterious effects of the compound, and identified five toxicity suppressors. These strains contained hypomorphic mutations in each of the known components of the p38 MAP kinase cassette (tir-1, nsy-1, sek-1, and pmk 1), demonstrating that hyperstimulation of the p38 MAPK pathway is toxic to animals. To explore mechanisms of immune pathway regulation in C. elegans, we conducted another genetic screen for dominant activators of the p38 MAPK pathway, and identified a single allele that had a gain-of-function (gf) mutation in nsy 1, the MAP kinase kinase kinase that acts upstream of p38 MAPK pmk-1. The nsy 1(gf) allele caused hyperinduction of p38 MAPK PMK-1-dependent immune effectors, had greater levels of phosphorylated p38 MAPK, and was more resistant to killing by the bacterial pathogen Pseudomonas aeruginosa compared to wild-type controls. In addition, the nsy-1(gf) mutation was toxic to developing animals. Together, these data suggest that the activity of the MAPKKK NSY-1 is tightly regulated as part of a physiological mechanism to control p38 MAPK-mediated innate immune hyperactivation, and ensure cellular homeostasis in C. elegans. PMID- 26818075 TI - Genome-Wide Analysis of Transposon and Retroviral Insertions Reveals Preferential Integrations in Regions of DNA Flexibility. AB - DNA transposons and retroviruses are important transgenic tools for genome engineering. An important consideration affecting the choice of transgenic vector is their insertion site preferences. Previous large-scale analyses of Ds transposon integration sites in plants were done on the basis of reporter gene expression or germ-line transmission, making it difficult to discern vertebrate integration preferences. Here, we compare over 1300 Ds transposon integration sites in zebrafish with Tol2 transposon and retroviral integration sites. Genome wide analysis shows that Ds integration sites in the presence or absence of marker selection are remarkably similar and distributed throughout the genome. No strict motif was found, but a preference for structural features in the target DNA associated with DNA flexibility (Twist, Tilt, Rise, Roll, Shift, and Slide) was observed. Remarkably, this feature is also found in transposon and retroviral integrations in maize and mouse cells. Our findings show that structural features influence the integration of heterologous DNA in genomes, and have implications for targeted genome engineering. PMID- 26818076 TI - Environmental Association Analyses Identify Candidates for Abiotic Stress Tolerance in Glycine soja, the Wild Progenitor of Cultivated Soybeans. AB - Natural populations across a species range demonstrate population structure owing to neutral processes such as localized origins of mutations and migration limitations. Selection also acts on a subset of loci, contributing to local adaptation. An understanding of the genetic basis of adaptation to local environmental conditions is a fundamental goal in basic biological research. When applied to crop wild relatives, this same research provides the opportunity to identify adaptive genetic variation that may be used to breed for crops better adapted to novel or changing environments. The present study explores an ex situ conservation collection, the USDA germplasm collection, genotyped at 32,416 SNPs to identify population structure and test for associations with bioclimatic and biophysical variables in Glycine soja, the wild progenitor of Glycine max (soybean). Candidate loci were detected that putatively contribute to adaptation to abiotic stresses. The identification of potentially adaptive variants in this ex situ collection may permit a more targeted use of germplasm collections. PMID- 26818077 TI - Increasing Genome Sampling and Improving SNP Genotyping for Genotyping-by Sequencing with New Combinations of Restriction Enzymes. AB - Genotyping-by-sequencing (GBS) has emerged as a useful genomic approach for exploring genome-wide genetic variation. However, GBS commonly samples a genome unevenly and can generate a substantial amount of missing data. These technical features would limit the power of various GBS-based genetic and genomic analyses. Here we present software called IgCoverage for in silico evaluation of genomic coverage through GBS with an individual or pair of restriction enzymes on one sequenced genome, and report a new set of 21 restriction enzyme combinations that can be applied to enhance GBS applications. These enzyme combinations were developed through an application of IgCoverage on 22 plant, animal, and fungus species with sequenced genomes, and some of them were empirically evaluated with different runs of Illumina MiSeq sequencing in 12 plant species. The in silico analysis of 22 organisms revealed up to eight times more genome coverage for the new combinations consisted of pairing four- or five-cutter restriction enzymes than the commonly used enzyme combination PstI + MspI. The empirical evaluation of the new enzyme combination (HinfI + HpyCH4IV) in 12 plant species showed 1.7-6 times more genome coverage than PstI + MspI, and 2.3 times more genome coverage in dicots than monocots. Also, the SNP genotyping in 12 Arabidopsis and 12 rice plants revealed that HinfI + HpyCH4IV generated 7 and 1.3 times more SNPs (with 0 16.7% missing observations) than PstI + MspI, respectively. These findings demonstrate that these novel enzyme combinations can be utilized to increase genome sampling and improve SNP genotyping in various GBS applications. PMID- 26818079 TI - What is an RNA? A top layer for RNA classification. AB - Every ribonucleic acid begins its cellular life as a transcript. If the transcript or its processing product has a function it should be regarded an RNA. Nonfunctional transcripts, by-products from processing, degradation intermediates, even those originating from (functional) RNAs, and non-functional products of transcriptional gene regulation accomplished via the act of transcription, as well as stochastic (co)transcripts could simply be addressed as transcripts (class 0). The copious functional RNAs (class I), often maturing after one or more processing steps, already are systematized into ever expanding sub-classifications ranging from micro RNAs to rRNAs. Established sub classifications addressing a wide functional diversity remain unaffected. mRNAs (class II) are distinct from any other RNA by virtue of their potential to be translated into (poly)peptide(s) on ribosomes. We are not proposing a novel RNA classification, but wish to add a basic concept with existing terminology (transcript, RNA, and mRNA) that should serve as an additional framework for carefully delineating RNA function from an avalanche of RNA sequencing data. At the same time, this top level hierarchical model should illuminate important principles of RNA evolution and biology thus heightening our awareness that in biology boundaries and categorizations are typically fuzzy. PMID- 26818078 TI - Field-Based High-Throughput Plant Phenotyping Reveals the Temporal Patterns of Quantitative Trait Loci Associated with Stress-Responsive Traits in Cotton. AB - The application of high-throughput plant phenotyping (HTPP) to continuously study plant populations under relevant growing conditions creates the possibility to more efficiently dissect the genetic basis of dynamic adaptive traits. Toward this end, we employed a field-based HTPP system that deployed sets of sensors to simultaneously measure canopy temperature, reflectance, and height on a cotton (Gossypium hirsutum L.) recombinant inbred line mapping population. The evaluation trials were conducted under well-watered and water-limited conditions in a replicated field experiment at a hot, arid location in central Arizona, with trait measurements taken at different times on multiple days across 2010-2012. Canopy temperature, normalized difference vegetation index (NDVI), height, and leaf area index (LAI) displayed moderate-to-high broad-sense heritabilities, as well as varied interactions among genotypes with water regime and time of day. Distinct temporal patterns of quantitative trait loci (QTL) expression were mostly observed for canopy temperature and NDVI, and varied across plant developmental stages. In addition, the strength of correlation between HTPP canopy traits and agronomic traits, such as lint yield, displayed a time dependent relationship. We also found that the genomic position of some QTL controlling HTPP canopy traits were shared with those of QTL identified for agronomic and physiological traits. This work demonstrates the novel use of a field-based HTPP system to study the genetic basis of stress-adaptive traits in cotton, and these results have the potential to facilitate the development of stress-resilient cotton cultivars. PMID- 26818081 TI - Prisoners' access to psychoactive medications: The need for research and improved policy. PMID- 26818080 TI - Using the simple sample count to estimate the frequency of prescription drug neuroenhancement in a sample of Jordan employees. AB - BACKGROUND: Epidemiological research indicates that the use of prescription drugs to enhance cognitive functioning is prevalent in Western countries, however, research on this phenomenon in Arab countries is lacking. Our study aimed to investigate the frequency of neuroenhancement (NE) using prescription drugs in a sample of employees in Jordan. METHODS: A sample of 1186 employees (37.11+/-8.37 years old, 495 female), of whom 723 (35.65+/-7.53 years old, 396 female) served as teachers, completed a paper-pencil questionnaire. The single sample count technique (SSC) was used in order to secure confidential, self-reporting of prescription drug NE. RESULTS: The 12-month prevalence of NE, estimated with the SSC was 15.43%. At 26.16%, the prevalence estimate was markedly higher in the subsample of teachers compared to non-teachers, 0.29%. Surprisingly, 336 participants did not use the SSC and directly affirmed or denied prescription drug NE. These direct responses yielded a prevalence of 11.57% for the full sample, 9.73% for the teachers and 15.60% for the non-teachers. CONCLUSION: This is the first study of the frequency of NE in an Arab sample. Results indicate that the use of prescription drug NE is not limited to Western countries and that teachers in Jordan might constitute a high-risk population. Further, participants seem to differ in their use of indirect estimation methods for reporting prescription drug NE. For future research, it might be useful to triangulate standard self-reports and indirect estimation methods to assess NE. Possible cultural differences and specific high-risk populations for NE should be investigated further. PMID- 26818082 TI - Circumstances and contexts of heroin initiation following non-medical opioid analgesic use in New York City. AB - BACKGROUND: As the prevalence of opioid analgesic (OA) misuse and associated harms have increased in the United States, the prevalence of heroin use and rates of unintentional overdose have concurrently risen. Research has begun to identify connections between OA misuse and heroin use, although this relationship remains under explored. The present study explores the context of heroin initiation among persons with histories of OA misuse in New York City. METHODS: In-depth interviews were conducted with 31 individuals with histories of OA misuse who initiated heroin use within the past five years. Data were collected between August 2013 and January 2015. All participants' OA misuse temporally preceded their heroin use. Interviews were coded and analyzed utilizing thematic qualitative methods. RESULTS: Participants ranged in age from 18 to 44 years; 25 identified as male and 30 identified as non-Hispanic white and heterosexual. All participants had stable housing at the time of interview and all were high school graduates. Participants described several key points of transition along their trajectories from OA misuse to heroin initiation: dual- to single-entity OAs; oral to intranasal OA administration; and the development of physical opioid dependence. Participants described the breaking down of heroin-related stigma across social networks as new drug use permeated social groups. CONCLUSION: Several points of transition were identified in participants' trajectories from OA misuse to heroin initiation. In particular the development of physical dependence was a critical factor as existing heroin stigma was rapidly overcome in the face of opioid withdrawal. The relatively short time to heroin initiation documented among new user groups serves as an added challenge to the development of interventions. PMID- 26818083 TI - Non-prescribed use of opioid substitution medication: Patterns and trends in sub populations of opioid users in Germany. AB - BACKGROUND: Non-prescribed use of opioid substitution medication (NPU) appears to represent a relevant source of opioids among European drug users. Little is known about the prevalence of NPU in Germany and possible differences between subgroups of opioid users. The present study examines NPU and other drug use patterns among drug consumption room (DCR) clients, opioid substituted DCR clients, and patients recruited in opioid substitution treatment (OST) practices. METHODS: Cross sectional data was collected in 2011 from 842 opioid users in 10 DCRs and 12 OST practices across 11 German cities. Structured interviews comprised indicators for socio-demographics, health status, drug use, motives for NPU, and the availability and price of illicit substitution medication. Group differences were examined with one-way ANOVAs, chi-square tests, or t-tests, and factors for NPU were included in a multivariate model. Over-time comparisons were performed with similar data collected in 2008. RESULTS: Lifetime, 30-day and 24-h NPU prevalence for the total sample was 76.5%, 21.9%, and 9.3%, respectively, with methadone being the most frequently used substance. NPU, poly-drug use and injection drug use were more common among DCR clients, especially among DCR clients not in OST. The three groups featured distinct socio-demographic characteristics, with substituted patients being more socially integrated, while few differences in health parameters emerged. Motives for NPU were mostly related to potential shortcomings of OST, such as insufficient dosages, difficulties with transportation, and lack of access. NPU prevalence was found to be higher than in 2008, while injection rate of substitution medication was similarly low. Main factors associated with NPU were not being in OST, past 24-h use of other drugs, and younger age. CONCLUSION: Although diverted methadone or buprenorphine are rarely used as main drugs, NPU is prevalent among opioid users, particularly among DCR clients not in OST. OST reduces NPU if opioid users' needs are met. PMID- 26818085 TI - Impaired awareness of hypoglycaemia in subjects with type 1 diabetes. Results of an online survey in a diabetes web site. AB - OBJECTIVE: To assess the frequency of impaired awareness of hypoglycaemia (IAH) using a specific questionnaire (Spanish version) in a free access diabetes related web site. METHODS: Data from a free access Spanish version of the Clarke test previously uploaded to the website of the Fundacion para la Diabetes (March 2014-January 2015) were assessed. In addition to the eight questions in Clarke's questionnaire, information on type of diabetes, age, and disease duration was obtained. The Clarke test divided participants into three categories: normal awareness, uncertain and IAH. RESULTS: Of the 418 participants with type 1 diabetes, 51.2% were aged 36-55 years. In 34.7%, diabetes had been diagnosed >15 years before, while disease duration was <2 years in 11%. According to Clarke categories, 23.4% had IAH, 15.3% uncertain awareness, and 61.3% normal awareness. The longer the duration of diabetes, the higher the Clarke test score. According to the Clarke test, 14.1% of participants had experienced at least one episode of severe hypoglycaemia in the previous year, and half of these (7.4%) had suffered severe hypoglycaemia two or more times. All but one of the participants with two or more episodes of severe hypoglycaemia had IAH. CONCLUSIONS: Our study shows that the rate of IAH using an online survey is similar (25%) to that previously reported in other geographical areas, increases with diabetes duration, and identifies subjects prone to severe hypoglycaemia. PMID- 26818084 TI - E-cigarette advertisements, and associations with the use of e-cigarettes and disapproval or quitting of smoking: Findings from the International Tobacco Control (ITC) Netherlands Survey. AB - BACKGROUND: Much attention has been directed towards the possible effects of e cigarette advertisements on adolescent never smokers. However, e-cigarette advertising may also influence perceptions and behaviours of adult smokers. The aim of our study was to examine whether noticing e-cigarette advertisements is associated with current use of e-cigarettes, disapproval of smoking, quit smoking attempts, and quit smoking success. METHODS: We used longitudinal data from two survey waves of the ITC Netherlands Survey among smokers aged 16 years and older (n=1198). Respondents were asked whether they noticed e-cigarettes being advertised on television, on the radio, and in newspapers or magazines in the previous 6 months. RESULTS: There was a significant increase in noticing e cigarette advertisements between 2013 (13.3%) and 2014 (36.0%), across all media. The largest increase was for television advertisements. There was also a substantial increase in current use of e-cigarettes (from 3.1% to 13.3%), but this was not related to noticing advertisements in traditional media (OR=0.99, p=0.937). Noticing advertisements was bivariately associated with more disapproval of smoking (Beta=0.05, p=0.019) and with a higher likelihood of attempting to quit smoking (OR=1.37, p=0.038), but these associations did not reach significance in multivariate analyses. There was no significant association between noticing advertisements and quit smoking success in either the bivariate or multivariate regression analysis (OR=0.92, p=0.807). CONCLUSION: Noticing e cigarette advertisements increased sharply in the Netherlands between 2013 and 2014 along with increased e-cigarette use, but the two appear unrelated. The advertisements did not seem to have adverse effects on disapproval of smoking and smoking cessation. PMID- 26818086 TI - Lipid changes and their relationship with vitamin D levels in children under 18 years with type 1 diabetes. AB - OBJECTIVE: To analyze lipid changes and their relationship with 25-hydroxy vitamin D3 (25-OH-D) levels in patients under 18 years old with type 1 diabetes mellitus (T1DM). MATERIAL AND METHODS: A cross-sectional, descriptive study. Patients under 18 years with T1DM were enrolled by consecutive, nonrandomized sampling. Data collected included sex, age, pubertal stage, time since T1DM onset, weight, height, body mass index (BMI), waist circumference, glycosylated hemoglobin (HbA1c), 25-OH-D, total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides (TG). Results were stratified by sex, age, and pubertal stage. Data were analyzed using SPSS((r)). RESULTS: Ninety patients with a mean age of 11.7 +/- 3.6 years (51.1% males) and mean HbA1c levels of 7.5 +/- 1.3% were enrolled. Of these, 26.6% had 25-OH-D levels<20 ng/mL and 13.3% 25 OH-D levels <= 15 ng/mL. No differences were found in 25-OH-D between patients with overweight or obesity and the rest. HDL-C levels<40 ng/mL were found in 1.1%, 34.4% had LDL-C levels >= 100 mg/dL, and 2.2% had TG levels >= 150 mg/dL. Patients with 25-OH-D<20 ng/mL had higher TG levels than the rest (76.80 +/- 45.62 vs 57.55 +/- 26.08; P=.04) in the multivariate analysis controlled for BMI, waist circumference, and HbA1c. A correlation was found between 25-OH-D and TG levels (-0.230; P=.029). CONCLUSIONS: Patients in our population with vitamin D deficiency had higher TG levels. Long-term follow-up should be performed to understand the potential impact of such levels on diabetes-related complications. PMID- 26818087 TI - Loss of phospholipase D2 impairs VEGF-induced angiogenesis. AB - Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis and critical for normal embryonic development and repair of pathophysiological conditions in adults. Although phospholipase D (PLD) activity has been implicated in angiogenic processes, its role in VEGF signaling during angiogenesis in mammals is unclear. Here, we found that silencing of PLD2 by siRNA blocked VEGF mediated signaling in immortalized human umbilical vein endothelial cells (iHUVECs). Also, VEGF-induced endothelial cell survival, proliferation, migration, and tube formation were inhibited by PLD2 silencing. Furthermore, while Pld2-knockout mice exhibited normal development, loss of PLD2 inhibited VEGF-mediated ex vivo angiogenesis. These findings suggest that PLD2 functions as a key mediator in the VEGF-mediated angiogenic functions of endothelial cells. [BMB Reports 2016; 49(3): 191-196]. PMID- 26818088 TI - Induction of MAP kinase phosphatase 3 through Erk/MAP kinase activation in three oncogenic Ras (H-, K- and N-Ras)-expressing NIH/3T3 mouse embryonic fibroblast cell lines. AB - Ras oncoproteins are small molecular weight GTPases known for their involvement in oncogenesis, which operate in a complex signaling network with multiple effectors. Approximately 25% of human tumors possess mutations in a member of this family. The Raf1/MEK/Erk1/2 pathway is one of the most intensively studied signaling mechanisms. Different levels of regulation account for the inactivation of MAP kinases by MAPK phosphatases in a cell type- and stimuli-dependent manner. In the present study, using three inducible Ras-expressing NIH/3T3 cell lines, we demonstrated that MKP3 upregulation requires the activation of the Erk1/2 pathway, which correlates with the shutdown of this pathway. We also demonstrated, by applying pharmacological inhibitors and effector mutants of Ras, that induction of MKP3 at the protein level is positively regulated by the oncogenic Ras/Raf/MEK/Erk1/2 signaling pathway. [BMB Reports 2016; 49(7): 370 375]. PMID- 26818090 TI - Electronic transport properties of ultra-thin Ni and Ni-C nanowires. AB - The structures and electronic transport properties of ultra-thin Ni and Ni-C nanowires obtained from carbon nanotube (CNT) templates are theoretically investigated. C atoms tend to locate at the central positions of nanowires and are surrounded by Ni atoms. Spin polarization at the Fermi level is not responsible for the spin filtration of these nanowires. Increasing C concentration can improve the resistance of nanowires by abating the number of electronic transmission channels and the coupling of electron orbitals between Ni atoms. Moreover, with the increase of diameter, the conductance of these nanowires increases as well. This study is helpful for guiding the synthesis of nanowires with desired applications. PMID- 26818089 TI - Crotamine stimulates phagocytic activity by inducing nitric oxide and TNF-alpha via p38 and NFkappa-B signaling in RAW 264.7 macrophages. AB - Crotamine is a peptide toxin found in the venom of the rattlesnake Crotalus durissus terrificus and has antiproliferative, antimicrobial, and antifungal activities. Herein, we show that crotamine dose-dependently induced macrophage phagocytic and cytostatic activity by the induction of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha). Moreover, the crotamineinduced expression of iNOS and TNF-alpha is mediated through the phosphorylation of p38 and the NF-kappaB signaling cascade in macrophages. Notably, pretreatment with SB203580 (a p38-specific inhibitor) or BAY 11-7082 (an NF-kappaB inhibitor) inhibited crotamine-induced NO production and macrophage phagocytic and cytotoxic activity. Our results show for the first time that crotamine stimulates macrophage phagocytic and cytostatic activity by induction of NO and TNF-alpha via the p38 and NF-kappaB signaling pathways and suggest that crotamine may be a useful therapeutic agent for the treatment of inflammatory disease. [BMB Reports 2016; 49(3): 185-190]. PMID- 26818091 TI - Heating-Rate-Triggered Carbon-Nanotube-based 3-Dimensional Conducting Networks for a Highly Sensitive Noncontact Sensing Device. AB - Recently, flexible and transparent conductive films (TCFs) are drawing more attention for their central role in future applications of flexible electronics. Here, we report the controllable fabrication of TCFs for moisture-sensing applications based on heating-rate-triggered, 3-dimensional porous conducting networks through drop casting lithography of single-walled carbon nanotube (SWCNT)/poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate ( PEDOT: PSS) ink. How ink formula and baking conditions influence the self-assembled microstructure of the TCFs is discussed. The sensor presents high-performance properties, including a reasonable sheet resistance (2.1 kohm/sq), a high visible-range transmittance (>69%, PET = 90%), and good stability when subjected to cyclic loading (>1000 cycles, better than indium tin oxide film) during processing, when formulation parameters are well optimized (weight ratio of SWCNT to PEDOT: PSS: 1:0.5, SWCNT concentration: 0.3 mg/ml, and heating rate: 36 degrees C/minute). Moreover, the benefits of these kinds of TCFs were verified through a fully transparent, highly sensitive, rapid response, noncontact moisture-sensing device (5 * 5 sensing pixels). PMID- 26818092 TI - Iron signature in asbestos-induced malignant pleural mesothelioma: A population based autopsy study. AB - Malignant pleural mesothelioma (MPM) is an aggressive cancer with poor prognosis. The development of MPM is frequently linked to inhalation of asbestos fibers. A genetic component of susceptibility to this disease is suggested by the observation that some individuals develop MPM following lower doses of asbestos exposure, whereas others exposed to higher quantities do not seem to be affected. This hypothesis is supported also by frequent reports of MPM familial clustering. Despite the widely recognized role of iron (Fe) in cellular asbestos-induced pulmonary toxicity, the role of the related gene polymorphisms in the etiology of MPM has apparently not been evaluated. Eighty-six single-nucleotide polymorphisms (SNPs) of 10 Fe-metabolism genes were examined by exploiting formalin-fixed paraffin-embedded postmortem samples from 77 patients who died due to MPM (designated AEM) and compared with 48 who were exposed to asbestos but from died in old age of cause other than asbestos (designated AENM). All subjects showed objective signs of asbestos exposure. Three SNPs, localized in the ferritin heavy polypeptide, transferrin, and hephaestin genes, whose frequencies were distributed differently in AEM and AENM populations, were identified. For ferritin and transferrin the C/C and the G/G genotypes, respectively, representing intronic polymorphisms, were significantly associated with protection against MPM and need to be considered as possible genetic markers of protection. Similarly, the C/C hephaestin SNP, a missense variation of this multicopper ferroxidase encoding gene, may be related, also functionally, with protection against MPM. In conclusion, it is proposed that three Fe metabolism associated genes, significantly associated with protection against development of MPM, may serve as protective markers for this aggressive tumor. PMID- 26818093 TI - Colonization of Rhodnius prolixus gut by Trypanosoma cruzi involves an extensive parasite killing. AB - Trypanosoma cruzi, the etiological agent of Chagas disease, is ingested by triatomines during their bloodmeal on an infected mammal. Aiming to investigate the development and differentiation of T. cruzi inside the intestinal tract of Rhodnius prolixus at the beginning of infection we fed insects with cultured epimastigotes and blood trypomastigotes from infected mice to determine the amount of recovered parasites after ingestion. Approximately 20% of the ingested parasites was found in the insect anterior midgut (AM) 3 h after feeding. Interestingly, a significant reduction (80%) in the numbers of trypomastigotes was observed after 24 h of infection suggesting that parasites were killed in the AM. Moreover, few parasites were found in that intestinal portion after 96 h of infection. The evaluation of the numbers of parasites in the posterior midgut (PM) at the same periods showed a reduced parasite load, indicating that parasites were not moving from the AM. Additionally, incubation of blood trypomastigotes with extracts from R. prolixus AMs revealed that components of this tissue could induce significant death of T. cruzi. Finally, we observed that differentiation from trypomastigotes to epimastigotes is not completed in the AM; instead we suggest that trypomastigotes change to intermediary forms before their migration to the PM, where differentiation to epimastigotes takes place. The present work clarifies controversial points concerning T. cruzi development in insect vector, showing that parasite suffers a drastic decrease in population size before epimastigonesis accomplishment in PM. PMID- 26818095 TI - Misdiagnosis in Hypoplastic Sinus of Valsalva with Localized Aneurysm: A Diagnostic Pitfall in Computed Tomography. PMID- 26818094 TI - TRPV6 plays a new role in predicting survival of patients with esophageal squamous cell carcinoma. AB - BACKGROUND: TRPV6 is over-expressed and promotes the proliferation and invasion in many cancers. The association between the expression of TRPV6 and clinical outcome in esophageal squamous cell carcinoma (ESCC) has not been studied yet. We aim to elucidate the role of TRPV6 in predicting prognosis of patients with ESCC. METHODS: In the retrospective study, mRNA level of TRPV6 was examined in patients (N = 174) from Sun Yat-sen University Cancer Center (mRNA cohort) and protein level of TRPV6 was examined in patients (N = 218) from Linzhou Cancer Hospital (protein cohort). Statistical analysis was performed to test the clinical and prognostic significance of TRPV6. RESULTS: TRPV6 was down-regulated in ESCC tissues and cell lines. Patients with downregulation of TRPV6 trended to have a higher rate of advanced pT stage in both mRNA cohort (P = 0.089) and protein cohort (P = 0.073), though not statistically significant. No significant association was observed between TRPV6 expression and disease-specific survival (DSS) in both two cohorts. However, stratified survival analysis based on the gender showed that in mRNA cohort, downregulation of TRPV6 was associated with an unfavorable 3-year DSS in patients with male (47.3 % vs 63.6 %, P = 0.027) and with favorable 3-year DSS in patients with female (66.7 % vs 43.0 %, P = 0.031). The result was confirmed in protein cohort. Male patients with downregulation of TRPV6 had a poor 3-year DSS (20.0 % vs 57.1 %,P < 0.001) while female counterparts showed an enhanced 3-year DSS (56.1 % vs 28.6 %, P = 0.005). CONCLUSION: TRPV6 is down-regulated in ESCC. As a predictive biomarker, TRPV6 plays a Janus-like role in predicting survival of male and female ESCC patients. PMID- 26818096 TI - Mirtazapine does not improve sleep disorders in Alzheimer's disease: results from a double-blind, placebo-controlled pilot study. AB - AIM: The aim of this study was to test the efficacy and safety of mirtazapine in the treatment of sleep disorders in patients with Alzheimer's disease by means of a randomized, double-blind, placebo-controlled trial. Measurements were obtained for 7 days before intervention (baseline) and for 2 weeks after the onset of treatment. METHODS: Alzheimer's disease patients with sleep disorders (n = 24) received 15-mg mirtazapine (n = 8) or placebo (n = 16) once daily at 2100 hours for 2 weeks. Patients were evaluated with actigraphy and structured scales before and after intervention. Historical control was employed. RESULTS: Treatment with mirtazapine or placebo had no effect on cognitive and functional status as assessed by the Mini-Mental State Examination and the Katz scale, respectively. There were no differences between groups in the frequency or severity of the adverse events reported. Compared with the placebo group, mirtazapine users showed increased daytime sleepiness but no improvement in the duration or efficiency of nocturnal sleep after treatment. CONCLUSIONS: This study showed no significant therapeutic effects of 15-mg mirtazapine in community-dwelling Alzheimer's disease patients with sleep disorders. Instead, this study found evidence of worsening of daytime sleep patterns. PMID- 26818097 TI - Genetic diversity of Culex pipiens mosquitoes in distinct populations from Europe: contribution of Cx. quinquefasciatus in Mediterranean populations. AB - BACKGROUND: Mosquitoes of the Culex pipiens complex are cosmopolitan, and important vectors of neglected tropical diseases, such as arbovirosis and lymphatic filariasis. Among the complex taxa, Cx. pipiens (with two forms pipiens and molestus) and Cx. quinquefasciatus are the most ubiquitous mosquitoes in temperate and tropical regions respectively. Mosquitoes of this taxa lack of morphological differences between females, but have frank behavioral and physiological differences and have different trophic preferences that influence their vectorial status. Hybridization may change the vectorial capacity of these mosquitoes, increasing vector efficiency and medical importance of resulting hybrids. METHODS: Culex pipiens s.l. from 35 distinct populations were investigated by the study of mtDNA, symbiotic bacterium Wolbachia pipientis, nuclear DNA and flanking region of microsatellite CQ11 polymorphism using PCR with diagnostic primers, RFLP analysis and sequencing. RESULTS: Six different mitochondrial haplotypes were revealed by sequencing of the cytochrome oxidase subunit I (COI) gene and three different Wolbachia (wPip) groups were identified. A strong association was observed between COI haplotypes/groups, wPip groups and taxa; haplogroup A and infection with wPipII appear to be typical for Cx. pipiens form pipiens, haplotype D and infection with wPipIV for form molestus, while haplogroup E, characteristic of Cx. quinquefasciatus, were correlated with wPipI and found in Cx. pipiens sl. from coastal regions of Southern Europe and Mediterranean region. Analysis of microsatellite locus and nuclear DNA revealed hybrids between Cx. pipiens form pipiens and form molestus, as well as between Cx. pipiens and Cx. quinquefasciatus, in Mediterranean populations, as opposed to Northern Europe. Phylogenetic analysis of COI sequences yielded a tree topology that supported the RFLP analysis with significant bootstrap values for haplotype D and haplogroup E. CONCLUSIONS: Molecular identification provides the first evidence of the presence of hybrids between Cx. quinquefasciatus and Cx. pipiens as well as cytoplasmic introgression of Cx. quinquefasciatus into Cx. pipiens as a result of hybridization events in coastal regions of Southern Europe and Mediterranean region. Together with observed hybrids between pipiens and molestus forms, these findings point to the presence of hybrids in these areas, with consequent higher potential for disease transmission. PMID- 26818098 TI - Psychometric properties of Patient Reported Outcome Measures (PROMs) in patients diagnosed with Acute Respiratory Distress Syndrome (ARDS). AB - BACKGROUND: The aim of this study was to assess the psychometric properties of the EQ-5D-3 L, the SF-12 v2 and its preference based derivative the SF-6D, and the St Georges Respiratory Questionnaire (SGRQ), in patients diagnosed with Acute Respiratory Distress Syndrome (ARDS). METHODS: Data from the Oscillation in ARDS (OSCAR) randomised unblinded clinical trial of 795 patients diagnosed with ARDS provided the foundation of this secondary psychometric analysis. The three source patient reported outcome measures (PROMs) (EQ-5D-3 L, SF-12 and SGRQ) were collected at both 6 and 12 months post randomisation. All measures were tested for acceptability, reliability, internal consistency, validity and responsiveness. Data from responders at 6 months was used to test for acceptability, reliability, known groups validity and internal responsiveness. Data from patients who responded at both 6 and 12 months was used to test for convergent validity and external responsiveness. RESULTS: Rates of response at both 6 and 12 months post randomisation were 89.88 % for the EQ-5D-3 L, 77.38 % for the SF-6D, 71.43 % for both the physical and mental components of the SF-12 and 38.10 % for the SGRQ. All measures had a Cronbach's Alpha statistic higher than 0.7. For known group's validity, there was no difference in mean summary or utility scores between known groups for all PROMs with minimal effect sizes. All three source measures showed strong convergent and discriminant validity. There was consistent evidence that the SF-6D is an empirically valid and efficient alternative to the EQ-5D-3 L. The EQ-5D-3 L and SGRQ were more responsive compared to the SF-12 and SF-6D with the EQ-5D-3 L generating greater effect sizes than the SGRQ. CONCLUSION: The PROMs explored in this study displayed varying psychometric properties in the context of ARDS. Further research should focus on shortening the SGRQ whilst still maintaining its psychometric properties and mapping between the SGRQ and preference-based measures for future application within economic evaluations of respiratory focused interventions. The selection ofa preferred PROM for evaluative studies within the ARDS context should ultimately depend on the relative importance placed on individual psychometric properties and the importance placed on generation of health utilities for economic evaluation purposes. PMID- 26818099 TI - Phenotypic Manifestation of Genetic Risk for Schizophrenia During Adolescence in the General Population. AB - IMPORTANCE: Schizophrenia is a highly heritable, polygenic condition characterized by a relatively diverse phenotype and frequent comorbid conditions, such as anxiety and depression. At present, limited evidence explains how genetic risk for schizophrenia is manifest in the general population. OBJECTIVE: To investigate the extent to which genetic risk for schizophrenia is associated with different phenotypes during adolescence in a population-based birth cohort. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Of 14,062 children in the birth cohort, genetic data were available for 9912 adolescents. Data were collected periodically from September 6, 1990, and collection is ongoing. Data were analyzed from March 4 to August 13, 2015. EXPOSURES: Polygenic risk scores (PRSs) for schizophrenia generated for individuals in the ALSPAC cohort using results of the second Psychiatric Genomics Consortium Schizophrenia genome-wide association study as a training set. MAIN OUTCOMES AND MEASURES: Logistic regression was used to assess associations between the schizophrenia PRS and (1) psychotic experiences (Psychosis-Like Symptom Interview at 12 and 18 years of age), (2) negative symptoms (Community Assessment of Psychic Experiences at 16.5 years of age), (3) depressive disorder (Development and Well-Being Assessment at 15.5 years of age), and (4) anxiety disorder (Development and Well-Being Assessment at 15.5 years of age) in adolescence. RESULTS: Of the 8230 ALSPAC participants whose genetic data passed quality control checks (51.2% male, 48.8% female), 3676 to 5444 participated in assessments from 12 to 18 years of age. The PRSs created using single-nucleotide polymorphisms with a training-set P <= .05 threshold were associated with negative symptoms (odds ratio [OR] per SD increase in PRS, 1.21; 95% CI, 1.08-1.36; R(2) = 0.007) and anxiety disorder (OR per SD increase in PRS, 1.17; 95% CI, 1.06- 1.29; R(2) = 0.005). No evidence was found of an association between schizophrenia PRS and psychotic experiences (OR per SD increase in PRS, 1.08; 95% CI, 0.98-1.19; R(2) = 0.001) or depressive disorder (OR per SD increase in PRS, 1.02; 95% CI, 0.91-1.13; R(2) = 0.00005). Results were mostly consistent across different training-set P value thresholds and using different cutoffs and measures of the psychopathological outcomes. CONCLUSIONS AND RELEVANCE: This study demonstrates polygenic overlaps between common genetic polymorphisms associated with schizophrenia and negative symptoms and anxiety disorder but not with psychotic experiences or depression. Because the genetic risk for schizophrenia appears to be manifest as anxiety and negative symptoms during adolescence, a greater focus on these phenotypes rather than on psychotic experiences might be required for prediction of transition in at-risk samples. PMID- 26818101 TI - Changes in social support predict emotional well-being in breast cancer survivors. AB - BACKGROUND: Breast cancer survivors who have completed surgery and adjuvant treatment have distinct social support needs that may relate to emotional health. There is little research on both levels of social support following treatment and the association between social support and emotional well-being over time following breast cancer diagnosis and treatment. The aims of this study were to assess (1) the direction and magnitude of change in social support quality and quantity and (2) the degree to which change in quality and quantity of social support predicted change in emotional well-being over time following completion of breast cancer treatment. METHODS: A sample of 157 female breast cancer survivors (Mage = 55, SD = 11 years) completed a baseline and a 1-year follow-up questionnaire assessing sociodemographic information, quality and quantity of social support, and emotional well-being including depression symptoms, stress, and positive and negative affect. RESULTS: Social support quantity significantly decreased over 1 year, while social support quality remained stable. Based on change score analyses, a decrease in social support quality was a significant predictor of increases in depression, stress, and negative affect, explaining an extra 4 to 6% of variance in the emotional well-being outcomes compared with social support quantity. CONCLUSIONS: This study highlights the decline in social support among recently treated female breast cancer survivors and the importance of maintaining high-quality social support for emotional well-being. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26818100 TI - Combined image guided monitoring the pharmacokinetics of rapamycin loaded human serum albumin nanoparticles with a split luciferase reporter. AB - Imaging guided techniques have been increasingly employed to investigate the pharmacokinetics (PK) and biodistribution of nanoparticle based drug delivery systems. In most cases, however, the PK profiles of drugs could vary significantly from those of drug delivery carriers upon administration in the blood circulation, which complicates the interpretation of image findings. Herein we applied a genetically encoded luciferase reporter in conjunction with near infrared (NIR) fluorophores to investigate the respective PK profiles of a drug and its carrier in a biodegradable drug delivery system. In this system, a prototype hydrophobic agent, rapamycin (Rapa), was encapsulated into human serum albumin (HSA) to form HSA Rapa nanoparticles, which were then labeled with Cy5 fluorophore to facilitate the fluorescence imaging of HSA carrier. Meanwhile, we employed transgenetic HN12 cells that were modified with a split luciferase reporter, whose bioluminescence function is regulated by Rapa, to reflect the PK profile of the encapsulated agent. It was interesting to discover that there existed an obvious inconsistency of PK behaviors between HSA carrier and rapamycin in vitro and in vivo through near infrared fluorescence imaging (NIFRI) and bioluminescence imaging (BLI) after treatment with Cy5 labeled HSA Rapa. Nevertheless, HSA Rapa nanoparticles manifested favorable in vivo PK and tumor suppression efficacy in a follow-up therapeutic study. The developed strategy of combining a molecular reporter and a fluorophore in this study could be extended to other drug delivery systems to provide profound insights for non-invasive real time evaluation of PK profiles of drug-loaded nanoparticles in pre-clinical studies. PMID- 26818102 TI - Ankle Range of Motion, Leg Pain, and Leg Edema Improvement in Patients With Venous Leg Ulcers. PMID- 26818103 TI - Trigeminal Nerve Stimulation for Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder. AB - OBJECTIVES: External stimulation of the trigeminal nerve (eTNS) is an emerging neuromodulation therapy for epilepsy and depression. Preliminary studies suggest it has an excellent safety profile and is associated with significant improvements in seizures and mood. Neuroanatomical projections of the trigeminal system suggest eTNS may alter activity in structures regulating mood, anxiety, and sleep. In this proof-of-concept trial, the effects of eTNS were evaluated in adults with posttraumatic stress disorder (PTSD) and comorbid unipolar major depressive disorder (MDD) as an adjunct to pharmacotherapy for these commonly co occurring conditions. MATERIALS AND METHODS: Twelve adults with PTSD and MDD were studied in an eight-week open outpatient trial (age 52.8 [13.7 sd], 8F:4M). Stimulation was applied to the supraorbital and supratrochlear nerves for eight hours each night as an adjunct to pharmacotherapy. Changes in symptoms were monitored using the PTSD Patient Checklist (PCL), Hamilton Depression Rating Scale (HDRS-17), Quick Inventory of Depressive Symptomatology (QIDS-C), and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). RESULTS: Over the eight weeks, eTNS treatment was associated with significant decreases in PCL (p = 0.003; median decrease of 15 points; effect size d 1.5), HDRS-17 (p < 0.001; 42% response rate, 25% remission; d 2.1), and QIDS-C scores (p < 0.001; d 1.8), as well as an improvement in quality of life (Q-LES-Q, p < 0.01). eTNS was well tolerated with few treatment emergent adverse events. CONCLUSIONS: Significant improvements in PTSD and depression severity were achieved in the eight weeks of acute eTNS treatment. This novel approach to wearable brain stimulation may have use as an adjunct to pharmacotherapy in these disorders if efficacy and tolerability are confirmed with additional studies. PMID- 26818104 TI - Redox status of the testes and sperm of rats following exposure to 2,5 hexanedione. AB - OBJECTIVES: Exposure to 2,5-hexanedione (2,5-HD) is well known to be associated with reproductive dysfunctions in both humans and animals. However, the role of oxidative stress in 2,5-HD-induced toxicity in testes and sperm has not yet been studied. METHODOLOGY: The present study investigated the influence of 2,5-HD on antioxidant systems in the testes and epididymal sperm of rats following exposure to 0, 0.25, 0.5, and 1% 2,5-HD in drinking water for 21 consecutive days. RESULTS: Administration of 0.5% 2,5-HD significantly (P < 0.05) decreased epididymis weight, whereas 1% 2,5-HD-treated rats showed significantly decreased body weight, testis, and epididymis weights compared with the control group. Exposure to 2,5-HD caused a significant dose-dependent increase in the activities of superoxide dismutase, catalase, and glutathione peroxidase in both testes and sperm compared with the control group. Moreover, 2,5-HD-exposed rats showed significant decrease in glutathione-S-transferase activity and glutathione level with concomitant significant elevation in the levels of hydrogen peroxide and malondialdehyde in both testes and sperm. Testicular and epididymal atrophy with significant, dose-dependent, decrease in epididymal sperm number, sperm motility, and viability were observed in 2,5-HD-treated rats. CONCLUSION: 2,5-HD exposure impaired testicular function and sperm characteristics by disruption of the antioxidant systems and consequently, increased oxidative stress in the treated rats. PMID- 26818105 TI - Raising the Barriers to Access to Medicines in the Developing World - The Relentless Push for Data Exclusivity. AB - Since the adoption of the WTO-TRIPS Agreement in 1994, there has been significant controversy over the impact of pharmaceutical patent protection on the access to medicines in the developing world. In addition to the market exclusivity provided by patents, the pharmaceutical industry has also sought to further extend their monopolies by advocating the need for additional 'regulatory' protection for new medicines, known as data exclusivity. Data exclusivity limits the use of clinical trial data that need to be submitted to the regulatory authorities before a new drug can enter the market. For a specified period, generic competitors cannot apply for regulatory approval for equivalent drugs relying on the originator's data. As a consequence, data exclusivity lengthens the monopoly for the original drug, impairing the availability of generic drugs. This article illustrates how the pharmaceutical industry has convinced the US and the EU to impose data exclusivity on their trade partners, many of them developing countries. The key arguments formulated by the pharmaceutical industry in favor of adopting data exclusivity and their underlying ethical assumptions are described in this article, analyzed, and found to be unconvincing. Contrary to industry's arguments, it is unlikely that data exclusivity will promote innovation, especially in developing countries. Moreover, the industry's appeal to a property rights claim over clinical test data and the idea that data exclusivity can prevent the generic competitors from 'free-riding' encounters some important problems: Neither legitimize excluding all others. PMID- 26818106 TI - Pre-operative PCC for non-bleeding patients on warfarin. PMID- 26818107 TI - A novel samarium(ii) complex bearing a dianionic bis(phenolate) cyclam ligand: synthesis, structure and electron-transfer reactions. AB - The reaction of the hexadentate dianionic 1,4,8,11-tetraazacyclotetradecane-based bis(phenolate) ligand, (tBu2ArO)2Me2-cyclam(2-), with [SmI2(thf )2] in thf resulted in the formation of the divalent samarium complex [Sm(kappa(6) {(tBu2ArO)2Me2-cyclam})] (1). X-ray diffraction studies revealed that after recrystallization from n-hexane/thf complex 1 has a monomeric structure and does not contain thf molecules coordinated to the Sm(II) center. However, UV-vis and (1)H NMR spectroscopy of 1 evidenced the formation of thf-solvated complexes in neat thf. Reductive studies show that complex 1 can act as a single electrontransfer reagent and form well-defined Sm(III) species. The reaction of 1 with several substrates, namely, TlBPh4, pyridine N-oxide, OPPh3, SPPh3 and bipyridines, are reported. Spectroscopy studies, including NMR, and single crystal X-ray diffraction data are in agreement with the formation of cationic Sm(III) species, monochalcogenide bridged Sm(III) complexes and Sm(III) complexes with bipyridine radical ligand, respectively. PMID- 26818108 TI - Electroreflectance imaging of gold-H3PO4 supercapacitors. Part II: microsupercapacitor ageing characterization. AB - This microsupercapacitor ageing study demonstrates the usefulness of the electroreflectance technique by quantifying local charge accumulation. Two separate devices with interdigitated electrodes were evaulated over a period of 4.1 million charge/discharge cycles. The key results are spatial mapping of charge accumulation in the gold electrodes derived from variation in the observed electrode reflectance. The nominal device exhibited little change in spatial distribution throughout the ageing cycle and serves as a comparison for the test device, which exhibited some nonuniform charge accumulation behavior. Further, an accelerated ageing test was completed by applying increasing voltage pulses up to 1.46 V to the device. Visual evidence of electrode ageing emerged in the reflectance distribution. An equivalent circuit model was developed to assess the evolution of individual circuit elements that correlate to the physical causes of ageing. PMID- 26818109 TI - Fibroblast-Mediated Collagen Remodeling Within the Tumor Microenvironment Facilitates Progression of Thyroid Cancers Driven by BrafV600E and Pten Loss. AB - Contributions of the tumor microenvironment (TME) to progression in thyroid cancer are largely unexplored and may illuminate a basis for understanding rarer aggressive cases of this disease. In this study, we investigated the relationship between the TME and thyroid cancer progression in a mouse model where thyroid specific expression of oncogenic BRAF and loss of Pten (Braf(V600E)/Pten(-/-)/TPO Cre) leads to papillary thyroid cancers (PTC) that rapidly progress to poorly differentiated thyroid cancer (PDTC). We found that fibroblasts were recruited to the TME of Braf(V600E)/Pten(-/-)/TPO-Cre thyroid tumors. Conditioned media from cell lines established from these tumors, but not tumors driven by mutant H-ras, induced fibroblast migration and proliferation in vitro Notably, the extracellular matrix of Braf(V600E)/Pten(-/-)/TPO-Cre tumors was enriched with stromal-derived fibrillar collagen, compared with wild-type or Hras-driven tumors. Further, type I collagen enhanced the motility of Braf(V600E)/Pten(-/ )/TPO-Cre tumor cells in vitro In clinical specimens, we found COL1A1 and LOX to be upregulated in PTC and expressed at highest levels in PDTC and anaplastic thyroid cancer. Additionally, increased expression levels of COL1A1 and LOX were associated with decreased survival in thyroid cancer patients. Overall, our results identified fibroblast recruitment and remodeling of the extracellular matrix as pivotal features of the TME in promoting thyroid cancer progression, illuminating candidate therapeutic targets and biomarkers in advanced forms of this malignancy. Cancer Res; 76(7); 1804-13. (c)2016 AACR. PMID- 26818110 TI - A semi-parametric statistical model for integrating gene expression profiles across different platforms. AB - BACKGROUND: Determining differentially expressed genes (DEGs) between biological samples is the key to understand how genotype gives rise to phenotype. RNA-seq and microarray are two main technologies for profiling gene expression levels. However, considerable discrepancy has been found between DEGs detected using the two technologies. Integration data across these two platforms has the potential to improve the power and reliability of DEG detection. METHODS: We propose a rank based semi-parametric model to determine DEGs using information across different sources and apply it to the integration of RNA-seq and microarray data. By incorporating both the significance of differential expression and the consistency across platforms, our method effectively detects DEGs with moderate but consistent signals. We demonstrate the effectiveness of our method using simulation studies, MAQC/SEQC data and a synthetic microRNA dataset. CONCLUSIONS: Our integration method is not only robust to noise and heterogeneity in the data, but also adaptive to the structure of data. In our simulations and real data studies, our approach shows a higher discriminate power and identifies more biologically relevant DEGs than eBayes, DEseq and some commonly used meta analysis methods. PMID- 26818112 TI - Rare incidence of Gorham disease with limited involvement of the maxilla: case report. PMID- 26818111 TI - Do measurements of inflammatory mediators in blood predict recurrence in patients with bisphosphonate-related osteonecrosis of the jaws? AB - Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is well-recognised, difficult to manage, and often recurs. The aim of this study was to examine the value of preoperative measurements of inflammatory mediators in blood in 212 patients with BRONJ who were studied prospectively. Multiple logistic regression analysis was used to assess the importance of the amounts of substances in the blood that are independently associated with the dependent variable "recurrence of BRONJ". The only factor that significantly influenced the development of recurrent BRONJ was reduction in the white cell count (p<0.0001; hazard ratio 5.324; 95% CI 2.373 to 11.945). Neither white cell counts nor C-reactive protein concentrations within or above the reference ranges were significantly associated with recurrent BRONJ. Patients whose white cell counts were lower than the reference range were at increased risk of recurrent BRONJ. This may be a marker of reduced immunocompetence, and additional prophylactic measures or treatment should be considered for these patients. PMID- 26818113 TI - Quality assurance review of training in oral and maxillofacial surgery by the General Medical Council: areas of good practice, requirements, and recommendations. AB - The purpose of this paper is to disseminate the outcome of the 2012/13 UK-wide quality assurance review of postgraduate training in oral and maxillofacial surgery (OMFS) by the General Medical Council (GMC), as part of its review of small specialties. OMF surgeons need to be aware of the evidence on which the conclusions are based, and to know about the strengths of the specialty and the areas for future development so that postgraduate training, and ultimately the outcomes for patients, can be improved. This paper, by the authors involved in the review, summarises the salient points and is not a verbatim report. PMID- 26818114 TI - Outfracture of the inferior turbinates during superior repositioning Le Fort I osteotomy with cone-beam computed tomographic analysis of the volume of the nasal cavity. AB - We have investigated the volumes of the nasal cavities of 35 patients treated with superior repositioning Le Fort I osteotomy by analysing cone-beam computed tomography (CT) data with a 3-dimensional reconstruction program to correlate changes in the volume of the nasal cavity that were associated with the maxillary superior repositioning and the role of outfracture of the inferior turbinates. The patients were treated at the Pusan National Dental Hospital during the 14 month period January 2011-March 2012.. The patients were divided into two groups, the first of which consisted of 20 patients who had superior repositioning of 4mm or more with a mean superior movement of 5.2mm and outfracture of the inferior turbinates (outfracture group). The second group consisted of 15 patients who also had more than 4mm impaction with a mean superior movement of 5.0mm and for whom outfracture was not done (no outfracture group). Nasal symptoms were investigated preoperatively and 6 months postoperatively using the Nasal Obstruction Symptom Evaluation (NOSE) scale, and 3-dimensional volumetric analysis was made using cone-beam CT data to assess changes in nasal volume. There were significant differences between the groups in volumetric changes (V1 V2) (p=0.001) but no significant differences between the sexes. The volume of the nasal cavity in the outfracture group decreased by 20% after superior repositioning, but that in the no outfracture group decreased by 33%. Among the 20 patients in the outfracture group not one complained of nasal symptoms postoperatively. We conclude that outfracture of the inferior turbinates should be considered when the amount of superior movement of maxilla is more than 4mm. PMID- 26818115 TI - A new scheme to discover functional associations and regulatory networks of E3 ubiquitin ligases. AB - BACKGROUND: Protein ubiquitination catalyzed by E3 ubiquitin ligases play important modulatory roles in various biological processes. With the emergence of high-throughput mass spectrometry technology, the proteomics research community embraced the development of numerous experimental methods for the determination of ubiquitination sites. The result is an accumulation of ubiquitinome data, coupled with a lack of available resources for investigating the regulatory networks among E3 ligases and ubiquitinated proteins. In this study, by integrating existing ubiquitinome data, experimentally validated E3 ligases and established protein-protein interactions, we have devised a strategy to construct a comprehensive map of protein ubiquitination networks. RESULTS: In total, 41,392 experimentally verified ubiquitination sites from 12,786 ubiquitinated proteins of humans have been obtained for this study. Additional 494 E3 ligases along with 1220 functional annotations and 28588 protein domains were manually curated. To characterize the regulatory networks among E3 ligases and ubiquitinated proteins, a well-established network viewer was utilized for the exploration of ubiquitination networks from 40892 protein-protein interactions. The effectiveness of the proposed approach was demonstrated in a case study examining E3 ligases involved in the ubiquitination of tumor suppressor p53. In addition to Mdm2, a known regulator of p53, the investigation also revealed other potential E3 ligases that may participate in the ubiquitination of p53. CONCLUSION: Aside from the ability to facilitate comprehensive investigations of protein ubiquitination networks, by integrating information regarding protein-protein interactions and substrate specificities, the proposed method could discover potential E3 ligases for ubiquitinated proteins. Our strategy presents an efficient means for the preliminary screen of ubiquitination networks and overcomes the challenge as a result of limited knowledge about E3 ligase regulated ubiquitination. PMID- 26818116 TI - Sunitinib treatment reduces tumor growth and limits changes in microvascular properties after minor surgical intervention in an in vivo model of secondary breast cancer growth in bone. AB - BACKGROUND AND OBJECTIVES: Surgical interventions can alter the balance between pro- and anti-angiogenic growth factors and thereby modulate tumor growth. Since the microcirculatory properties of tumors underlie organ-specific differences, the microhemodynamic characteristics of bone metastasis have not yet been fully described. Angiogenesis inhibitors are increasingly being used to treat advanced stages of cancer. We hypothesized that the anti-angiogenic drug sunitinib abrogates alterations in microvascular properties following a minor surgical intervention in an in vivo model of secondary breast cancer growth in the bone. METHODS: Intravital microscopy was performed over 25 days using a xenograft model of breast cancer tumor growth in the bone to determine changes in microvascular properties during sunitinib treatment. Mastectomy was performed on day 5 to evaluate the effect of a minor surgical trauma on tumor growth and microvascular properties. RESULTS: Anti-angiogenic therapy resulted in reduced tumor growth, decreased vascular density, and increased vascular diameters. Blood flow velocity remained constant while microvascular permeability temporarily increased after the surgical intervention. CONCLUSIONS: Administration of sunitinib reduced tumor growth and altered microcirculatory properties in a time-dependent manner. The observed dramatic increase in microvascular permeability after the surgical intervention may have implications for local tumor growth, and metastatic dissemination. J. Surg. Oncol. 2016;113:515-521. (c) 2016 Wiley Periodicals, Inc. PMID- 26818118 TI - Identifying micro-inversions using high-throughput sequencing reads. AB - BACKGROUND: The identification of inversions of DNA segments shorter than read length (e.g., 100 bp), defined as micro-inversions (MIs), remains challenging for next-generation sequencing reads. It is acknowledged that MIs are important genomic variation and may play roles in causing genetic disease. However, current alignment methods are generally insensitive to detect MIs. Here we develop a novel tool, MID (Micro-Inversion Detector), to identify MIs in human genomes using next-generation sequencing reads. RESULTS: The algorithm of MID is designed based on a dynamic programming path-finding approach. What makes MID different from other variant detection tools is that MID can handle small MIs and multiple breakpoints within an unmapped read. Moreover, MID improves reliability in low coverage data by integrating multiple samples. Our evaluation demonstrated that MID outperforms Gustaf, which can currently detect inversions from 30 bp to 500 bp. CONCLUSIONS: To our knowledge, MID is the first method that can efficiently and reliably identify MIs from unmapped short next-generation sequencing reads. MID is reliable on low coverage data, which is suitable for large-scale projects such as the 1000 Genomes Project (1KGP). MID identified previously unknown MIs from the 1KGP that overlap with genes and regulatory elements in the human genome. We also identified MIs in cancer cell lines from Cancer Cell Line Encyclopedia (CCLE). Therefore our tool is expected to be useful to improve the study of MIs as a type of genetic variant in the human genome. The source code can be downloaded from: http://cqb.pku.edu.cn/ZhuLab/MID . PMID- 26818117 TI - Ocular transient receptor potential channel function in health and disease. AB - Transient receptor potential (TRP) channels sense and transduce environmental stimuli into Ca(2+) transients that in turn induce responses essential for cell function and adaptation. These non-selective channels with variable Ca(2+) selectivity are grouped into seven different subfamilies containing 28 subtypes based on differences in amino acid sequence homology. Many of these subtypes are expressed in the eye on both neuronal and non-neuronal cells where they affect a host of stress-induced regulatory responses essential for normal vision maintenance. This article reviews our current knowledge about the expression, function and regulation of TRPs in different eye tissues. We also describe how under certain conditions TRP activation can induce responses that are maladaptive to ocular function. Furthermore, the possibility of an association between TRP mutations and disease is considered. These findings contribute to evidence suggesting that drug targeting TRP channels may be of therapeutic benefit in a clinical setting. We point out issues that must be more extensively addressed before it will be possible to decide with certainty that this is a realistic endeavor. Another possible upshot of future studies is that disease process progression can be better evaluated by profiling changes in tissue specific functional TRP subtype activity as well as their gene and protein expression. PMID- 26818119 TI - High efficiency integration of three-dimensional functional microdevices inside a microfluidic chip by using femtosecond laser multifoci parallel microfabrication. AB - High efficiency fabrication and integration of three-dimension (3D) functional devices in Lab-on-a-chip systems are crucial for microfluidic applications. Here, a spatial light modulator (SLM)-based multifoci parallel femtosecond laser scanning technology was proposed to integrate microstructures inside a given 'Y' shape microchannel. The key novelty of our approach lies on rapidly integrating 3D microdevices inside a microchip for the first time, which significantly reduces the fabrication time. The high quality integration of various 2D-3D microstructures was ensured by quantitatively optimizing the experimental conditions including prebaking time, laser power and developing time. To verify the designable and versatile capability of this method for integrating functional 3D microdevices in microchannel, a series of microfilters with adjustable pore sizes from 12.2 MUm to 6.7 MUm were fabricated to demonstrate selective filtering of the polystyrene (PS) particles and cancer cells with different sizes. The filter can be cleaned by reversing the flow and reused for many times. This technology will advance the fabrication technique of 3D integrated microfluidic and optofluidic chips. PMID- 26818120 TI - Association of HLA-DRB1 alleles with susceptibility to mixed connective tissue disease in Polish patients. AB - Mixed connective tissue disease (MCTD) is a systemic autoimmune disease, originally defined as a connective tissue inflammatory syndrome with overlapping features of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM) and systemic sclerosis (SSc), characterized by the presence of antibodies against components of the U1 small nuclear ribonucleoprotein (U1snRNP). The aim of the study was to assess the frequency of (high-resolution-typed) DRB1 alleles in a cohort of Polish patients with MCTD (n = 103). Identification of the variants potentially associated with risk and protection was carried out by comparison with the DKMS Polish Bone Marrow Donor Registry (41306 alleles). DRB1*15:01 (odds ratio (OR): 6.06; 95% confidence interval (CI) 4.55-8.06), DRB1*04 (OR: 3.69; 95% CI 2.69-5.01) and *09:01 (OR: 8.12; 95% CI 2.15-21.75) were identified as risk alleles for MCTD, while HLA DRB1*07:01 allele was found to be protective (OR: 0.50; 95% CI 0.28-0.83). The carrier frequency of the DRB1*01 was higher in MCTD patients compared with controls, although the differences were not statistically significant. Our results confirm the modulating influence of HLA-DRB1 genotypes on development of connective tissue diseases such as MCTD. PMID- 26818121 TI - Association of HLA-DQ alleles with the presence of an anti-beta2-glycoprotein I antibody in patients with recurrent miscarriage. AB - Immunogenetic studies have suggested that autoantibody production is commonly associated with particular human leukocyte antigens (HLA) class II genotypes in certain autoimmune diseases. The objective of this study was to investigate whether the production of anti-beta2-glycoprotein I antibody (abeta2GPI) was associated with particular HLA-DQ alleles in patients with recurrent miscarriage (RM). The HLA-DQ genotypes in 126 patients with RM were determined using the polymerase chain reaction-sequence-specific primer method. Both the IgG and IgM isotypes of abeta2GPI were measured via enzyme-linked immunosorbent assay. Positive results for either IgG or IgM on two occasions within an interval of 12 weeks were defined as antiphospholipid antibody-positive. The frequencies of the HLA-DQA1*01:02 [odds ratio (OR) 3.4, 95% confidence interval (CI) 1.6-7.0, Pc = 0.018] and HLA-DQB1*02:01 alleles (OR 4.6, 95% CI 2.1-10.2, Pc = 9.18 * 10(-4)) were significantly increased in abeta2GPI-positive RM patients compared with abeta2GPI-negative RM patients. These results suggest that the HLA-DQA1*0102 and HLA-DQB1*0201 alleles may be involved in the production of abeta2GPI in RM patients. PMID- 26818122 TI - The profile of HLA-DRB1 alleles in Arabs with type 1 diabetes; meta-analyses. AB - Genes from the HLA complex have a major contribution in type 1 diabetes (T1D), which results from an interplay between environmental and genetic factors. The latter can explain some of the geographic variability in T1D occurrence around the world. Of a particular importance in this regard are the HLA-DR, -DP and -DQ loci. Consequently, we aimed at elucidating the collective genetic profiles of various alleles relating to HLA-DRB1 and -DP in T1D patients throughout the Arab World using the tools of meta-analysis. As for HLA-DQA1 and DQB1 alleles; this analysis was completed and published previously (see Introduction). As a result of limited availability of relevant studies of the HLA-DP locus, only HLA-DRB1 alleles were tackled in this paper. Our study showed that significant increases in T1D risk resulted from harboring the alleles DRB1*03:01 and *04:05 (odds ratio 7.76 and 7.52, respectively). DRB1*04:01 and *04:02 were also predisposing for T1D in Arabs. Very strong evidence supported the protective effects of DRB1*10:01, *13:01, *15:02 and *16:01, with low heterogeneity and no publication bias. The results from the series of meta-analyses performed in this study help to complete the global genetic epidemiological map of T1D by providing statistically robust data from the Arab World. PMID- 26818124 TI - Identification of a novel HLA-A*02 allele, HLA-A*02:432, in a Chinese individual. AB - A*02:432 differs from A*02:07:01 by one nucleotide change at nucleotide 572 in exon 3 from G to C. PMID- 26818123 TI - HLA-A*02:06:21, a novel variant of HLA-A*02:06, discovered in a Taiwanese bone marrow hematopoietic stem cell donor. AB - One nucleotide substitution at residue 318 of the HLA-A*02:06:01:01 results in a new allele, HLA-A*02:06:21. PMID- 26818125 TI - Description of two new HLA-A alleles, HLA-A*02:572 and HLA-A*03:225. AB - Characterization of two new human-leukocyte antigen (HLA)-A alleles, A*02:572 and HLA-A*03:225. PMID- 26818126 TI - Harnessing Smartphone-Based Digital Phenotyping to Enhance Behavioral and Mental Health. PMID- 26818127 TI - Xinfeng capsule for the treatment of rheumatoid arthritis patients with decreased pulmonary function--a randomized controlled clinical trial. AB - OBJECTIVE: To determine the effectiveness and safety of Xinfeng Capsules (XFC) for the treatment of rheumatoid arthritis (RA) patients with decreased pulmonary function. METHODS: This was a randomized controlled clinical trial of 80 RA patients. Participants were assigned to the trial group (40 cases) and the control group (40 cases) by block randomization. The trial group was treated with XFC, three pills each time three times daily for 2 months. The control group was treated with tripterygium glycoside (TPT), two pills each time three times daily for 2 months. Both groups were followed up after 2 months. The clinical effects, changes in joint and pulmonary function, and quality of life before and after treatment were observed; safety indices were also evaluated. RESULTS: Pain, swelling, tenderness, and duration of morning stiffness of joints were obviously decreased after treatment in both the trial and the control groups compared with baseline (P<0.01). Compared with before treatment, hand grip strength increased significantly after treatment in the trial group (P=0.0000); pulmonary function parameters such as forced expiratory volume in the first second of expiration/forced vital capacity (FEV1/FVC), 50% of the expiratory flow of forced vital capacity (FEF50), carbon monoxide diffusing capacity (DLco) were increased (P<0.01 or P<0.05); measures of quality of life such as role-physical, body pain, vitality and mental health were also improved after treatment in the trial group (all P<0.05). Joint swelling in the trial group decreased compared with the control group (P=0.0043), while hand grip strength was increased after treatment (P=0.0000). The increase in FEF50, DLco, and the dimensions of quality of life such as vitality and mental health were all significantly greater in the trial group than the control group (P<0.05 or P<0.01). CONCLUSIONS: XFC not only relieved joint pain in RA patients, but also significantly improved the ventilation and diffusion function of the lungs. Therefore, XFC could improve the whole body function and enhance the quality of life of RA patients. PMID- 26818129 TI - Benchmarking the Wilmer general eye services clinics: baseline metrics for surgical and outpatient clinic volume in an educational environment. AB - BACKGROUND: The Wilmer General Eye Services (GES) at the Johns Hopkins Hospital is the clinic where residents provide supervised comprehensive medical and surgical care to ophthalmology patients. The clinic schedule and supervision structure allows for a progressive increase in trainee responsibility, with graduated autonomy and longitudinal continuity of care over the three years of ophthalmology residency training. This study sought to determine the number of cases the GES contributes to the resident surgical experiences. In addition, it was intended to create benchmarks for patient volumes, cataract surgery yield and room utilization as part of an educational initiative to introduce residents to metrics important for practice management. METHODS: The electronic surgical posting system database was explored to determine the numbers of cases scheduled for patients seen by residents in the GES. In addition, aggregated residents' self-reported Accreditation Council for Graduate Medical Education (ACGME) surgical logs were collected for comparison. Finally transactional databases were queried to determine clinic volumes of new and established patients. The proportion of resident surgeries (1(st) surgeon and assistant) provided by GES patients, cataract surgery yield and new patient rates were calculated. Data was collected from July 1(st), 2014 until March 31(st), 2015 for all 16 residents (6 third year, 5 second year and 5 first year). RESULTS: The percentage of cataract, oculoplastics, cornea and glaucoma surgeries in which a resident was 1(st) surgeon and the patient came from the GES was 91.3, 76.1, 65.6, and 93.9 respectively. The new patient rate was 28.1% and room utilization was 50.4%. Cataract surgery yield was 29.2 DISCUSSION: The GES provides a significant proportion of primary surgeon opportunities for the residents, and in some instances, the majority of cases. Compared to benchmarks available for private practices, the new patient rate is high while the cataract surgery yield is low. The room utilization is lower than the 85% preferred by the hospital system. These are the first benchmarks of this type for an academic resident ophthalmology practice in the United States. CONCLUSIONS: Our study suggests that resident-hosted clinics can provide the majority of surgical opportunities for ophthalmology trainees, particulary with regard to cataract cases. However, because our study is the first academic resident practice to publish metrics of the type used in private practices, it is impossible to determine where our clinic stands compared to other training programs. Therefore, the authors strongly encourage ophthalmology training programs to explore and publish practice metrics. This will permit the creation of a benchmarking program that could be used to quantify efforts at enhancing ophthalmic resident education. PMID- 26818128 TI - Treatment outcomes in a safety observational study of dihydroartemisinin/piperaquine (Eurartesim((r))) in the treatment of uncomplicated malaria at public health facilities in four African countries. AB - BACKGROUND: Dihydroartemisinin-piperaquine (DHA-PQ) is one of five WHO recommended artemisinin combination therapy (ACT) for the treatment of uncomplicated malaria. However, little was known on its post-registration safety and effectiveness in sub-Saharan Africa. DHA-PQ provides a long post-treatment prophylactic effect against re-infection; however, new infections have been reported within a few weeks of treatment, especially in children. This paper reports the clinical outcomes following administration of DHQ-PQ in real-life conditions in public health facilities in Burkina Faso, Ghana, Mozambique, and Tanzania for the treatment of confirmed uncomplicated malaria. METHODS: An observational, non-comparative, longitudinal study was conducted on 10,591 patients with confirmed uncomplicated malaria visiting public health facilities within seven health and demographic surveillance system sites in four African countries (Ghana, Tanzania, Burkina Faso, Mozambique) between September 2013 and April 2014. Patients were treated with DHA-PQ based on body weight and followed up for 28 days to assess the clinical outcome. A nested cohort of 1002 was intensely followed up. Clinical outcome was assessed using the proportion of patients who reported signs and symptoms of malaria after completing 3 days of treatment. RESULTS: A total of 11,097 patients were screened with 11,017 enrolled, 94 were lost to follow-up, 332 withdrew and 10,591 (96.1%) patients aged 6 months-85 years met protocol requirements for analysis. Females were 52.8 and 48.5% were <5 years of age. Malaria was diagnosed by microscopy and rapid diagnostic test in 69.8% and 29.9%, respectively. At day 28, the unadjusted risk of recurrent symptomatic parasitaemia was 0.5% (51/10,591). Most of the recurrent symptomatic malaria patients (76%) were children <5 years. The mean haemoglobin level decreased from 10.6 g/dl on day 1 to 10.2 g/dl on day 7. There was no significant renal impairment in the nested cohort during the first 7 days of follow-up with minimal non-clinically significant changes noted in the liver enzymes. CONCLUSION: DHA-PQ was effective and well tolerated in the treatment of uncomplicated malaria and provides an excellent alternative first-line ACT in sub Saharan Africa. PMID- 26818130 TI - Metasurface-based broadband hologram with high tolerance to fabrication errors. AB - With new degrees of freedom to achieve full control of the optical wavefront, metasurfaces could overcome the fabrication embarrassment faced by the metamaterials. In this paper, a broadband hologram using metasurface consisting of elongated nanoapertures array with different orientations has been experimentally demonstrated. Owing to broadband characteristic of the polarization-dependent scattering, the performance is verified at working wavelength ranging from 405 nm to 914 nm. Furthermore, the tolerance to the fabrication errors, which include the length and width of the elongated aperture, the shape deformation and the phase noise, has been theoretically investigated to be as large as 10% relative to the original hologram. We believe the method proposed here is promising in emerging applications such as holographic display, optical information processing and lithography technology etc. PMID- 26818132 TI - Corrigendum: High-performance n-type black phosphorus transistors with type control via thickness and contact-metal engineering. PMID- 26818131 TI - siRNAmod: A database of experimentally validated chemically modified siRNAs. AB - Small interfering RNA (siRNA) technology has vast potential for functional genomics and development of therapeutics. However, it faces many obstacles predominantly instability of siRNAs due to nuclease digestion and subsequently biologically short half-life. Chemical modifications in siRNAs provide means to overcome these shortcomings and improve their stability and potency. Despite enormous utility bioinformatics resource of these chemically modified siRNAs (cm siRNAs) is lacking. Therefore, we have developed siRNAmod, a specialized databank for chemically modified siRNAs. Currently, our repository contains a total of 4894 chemically modified-siRNA sequences, comprising 128 unique chemical modifications on different positions with various permutations and combinations. It incorporates important information on siRNA sequence, chemical modification, their number and respective position, structure, simplified molecular input line entry system canonical (SMILES), efficacy of modified siRNA, target gene, cell line, experimental methods, reference etc. It is developed and hosted using Linux Apache MySQL PHP (LAMP) software bundle. Standard user-friendly browse, search facility and analysis tools are also integrated. It would assist in understanding the effect of chemical modifications and further development of stable and efficacious siRNAs for research as well as therapeutics. siRNAmod is freely available at: http://crdd.osdd.net/servers/sirnamod. PMID- 26818133 TI - C-Glucopyranosyl-1,2,4-triazol-5-ones: synthesis and inhibition of glycogen phosphorylase. AB - Various C-glucopyranosyl-1,2,4-triazolones were designed as potential inhibitors of glycogen phosphorylase. Syntheses of these compounds were performed with O perbenzoylated glucose derivatives as precursors. High temperature ring closure of N(1)-carbamoyl-C-beta-D-glucopyranosyl formamidrazone gave 3-beta-D glucopyranosyl-1,2,4-triazol-5-one. Reaction of N(1)-tosyl-C-beta-D glucopyranosyl formamidrazone with ClCOOEt furnished 3-beta-D-glucopyranosyl-1 tosyl-1,2,4-triazol-5-one. In situ prepared beta-D-glucopyranosylcarbonyl isocyanate was transformed by PhNHNHBoc into 3-beta-D-glucopyranosyl-1-phenyl 1,2,4-triazol-5-one, while the analogous 1-(2-naphthyl) derivative was obtained from the unsubstituted triazolone by naphthalene-2-boronic acid in a Cu(II) catalyzed N-arylation. Test compounds were prepared by Zemplen deacylation. The new glucose derivatives had weak or no inhibition of rabbit muscle glycogen phosphorylase b: the best inhibitor was 3-beta-D-glucopyranosyl-1-(2-naphthyl) 1,2,4-triazol-5-one (Ki = 80 uM). PMID- 26818134 TI - Dual therapy of grazoprevir and elbasvir for the treatment of hepatitis C infection. AB - The impact of chronic hepatitis C (HCV) worldwide is expected to increase as the population infected with HCV ages and more undiagnosed individuals are identified and linked to care through nation-wide initiatives. The development of interferon free regimens involving the use of direct-acting antiviral agents, which disrupt key steps in viral replication, has revolutionized the treatment of chronic HCV infection. However, there remains a great medical need for HCV therapy that is of shorter duration, all-oral, with a high barrier to resistance, and highly effective for all patient populations including those with end-stage renal disease (ESRD) and cirrhosis. Grazoprevir, an HCV NS3/4A protease inhibitor and elbasvir, an NS5A inhibitor, have broad in vitro activity against most HCV genotypes and retain in vitro activity against many clinically relevant resistance-associated variants. The once daily regimen is well-tolerated and highly efficacious across wide-ranging patient populations including those with ESRD on hemodialysis. PMID- 26818135 TI - Inverse QSPR/QSAR Analysis for Chemical Structure Generation (from y to x). AB - Retrieving descriptor information (x information) from a value of an objective variable (y) is a fundamental problem in inverse quantitative structure-property relationship (inverse-QSPR) analysis but challenging because of the complexity of the preimage function. Herewith, we propose using a cluster-wise multiple linear regression (cMLR) model as a QSPR model for inverse-QSPR analysis. x information is acquired as a probability density function by combining cMLR and the prior distribution modeled with a mixture of Gaussians (GMMs). Three case studies were conducted to demonstrate various aspects of the potential of cMLR. It was found that the predictive power of cMLR was superior to that of MLR, especially for data with nonlinearity. Moreover, it turned out that the applicability domain could be considered since the posterior distribution inherits the prior distribution's feature (i.e., training data feature) and represents the possibility of having the desired property. Finally, a series of inverse analyses with the GMMs/cMLR was demonstrated with the aim to generate de novo structures having specific aqueous solubility. PMID- 26818136 TI - Hearing difficulty and tinnitus among U.S. workers and non-workers in 2007. AB - BACKGROUND: Hearing loss and tinnitus are two potentially debilitating physical conditions affecting many people in the United States. The purpose of this study was to estimate the prevalence of hearing difficulty, tinnitus, and their co occurrence within U.S. METHODS: Data from the 2007 National Health Interview Survey (NHIS) were examined. Weighted prevalence and adjusted prevalence ratios for self-reported hearing difficulty, tinnitus, and their co-occurrence were estimated and compared by demographic, among workers with and without occupational noise exposure, and across industries and occupations. RESULTS: Seven percent of U.S. workers never exposed to occupational noise had hearing difficulty, 5% had tinnitus and 2% had both conditions. However, among workers who had ever been exposed to occupational noise, the prevalence was 23%, 15%, and 9%, respectively (P < 0.0001). CONCLUSIONS: Hearing difficulty and tinnitus are prevalent in the U.S.; especially among noise-exposed workers. Improved strategies for hearing conservation or better implementation are needed. PMID- 26818137 TI - Understanding gambling related harm: a proposed definition, conceptual framework, and taxonomy of harms. AB - BACKGROUND: Harm from gambling is known to impact individuals, families, and communities; and these harms are not restricted to people with a gambling disorder. Currently, there is no robust and inclusive internationally agreed upon definition of gambling harm. In addition, the current landscape of gambling policy and research uses inadequate proxy measures of harm, such as problem gambling symptomology, that contribute to a limited understanding of gambling harms. These issues impede efforts to address gambling from a public health perspective. METHODS: Data regarding harms from gambling was gathered using four separate methodologies, a literature review, focus groups and interviews with professionals involved in the support and treatment of gambling problems, interviews with people who gamble and their affected others, and an analysis of public forum posts for people experiencing problems with gambling and their affected others. The experience of harm related to gambling was examined to generate a conceptual framework. The catalogue of harms experienced were organised as a taxonomy. RESULTS: The current paper proposes a definition and conceptual framework of gambling related harm that captures the full breadth of harms that gambling can contribute to; as well as a taxonomy of harms to facilitate the development of more appropriate measures of harm. CONCLUSIONS: Our aim is to create a dialogue that will lead to a more coherent interpretation of gambling harm across treatment providers, policy makers and researchers. PMID- 26818138 TI - Prevalence of depression and related social and physical factors amongst the Iranian elderly population in 2012. AB - AIM: Depression is the most common psychiatric disorder and the second most common cause of disability among older adults. The objective of the present study was to investigate the prevalence of depression and related social and physical factors in the Iranian elderly population in 2012. METHODS: In this cross sectional study, 1350 Iranian older adults aged older than 60 years were selected considering the gender proportion of the population of five out of 31 provinces of Iran. To define depression, the short form (15-item) of the Geriatric Depression Scale was administered. To analyze the data, logistic regression was carried out using stata software (version 12.0). RESULTS: From 1350 participants, 642 (47.5%) were men and the rest were women. The mean +/- SD age of the sample was 69 +/- 7 years. The prevalence of depression was 36.7% (42.5% in women and 30.2% in men). At the bivariate level, sex, educational level, marital status, satisfaction with income, occupation, relationship with the financial provider, leisure time, activities of daily living, and frequency of meeting with friends and relatives were factors determining the odds of depression. However, after multivariate control, marital status and educational level were removed from the final model. In contrast, smoking, which was insignificant at the bivariate level, became significant at the multivariate level. CONCLUSIONS: Depression has a high prevalence among the Iranian elderly population. Therefore, it is important that this vulnerable group is provided with access to supportive environments that involve active participation in occupational and social activities, which in turn help reduce the chance of suffering from depression. Geriatr Gerontol Int 2017; 17: 126-131. PMID- 26818141 TI - Detection of right ventricular ischemia by SPECT myocardial perfusion imaging. PMID- 26818139 TI - Developmental nicotine exposure disrupts dendritic arborization patterns of hypoglossal motoneurons in the neonatal rat. AB - Maternal smoking or use of other products containing nicotine during pregnancy can have significant adverse consequences for respiratory function in neonates. We have shown, in previous studies, that developmental nicotine exposure (DNE) in a model system compromises the normal function of respiratory circuits within the brainstem. The effects of DNE include alterations in the excitability and synaptic interactions of the hypoglossal motoneurons, which innervate muscles of the tongue. This study was undertaken to test the hypothesis that these functional consequences of DNE are accompanied by changes in the dendritic morphology of hypoglossal motoneurons. Hypoglossal motoneurons in brain stem slices were filled with neurobiotin during whole-cell patch clamp recordings and subjected to histological processing to reveal dendrites. Morphometric analysis, including the Sholl method, revealed significant effects of DNE on dendritic branching patterns. In particular, whereas within the first five postnatal days there was significant growth of the higher-order dendritic branches of motoneurons from control animals, the growth was compromised in motoneurons from neonates that were subjected to DNE. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1125-1137, 2016. PMID- 26818140 TI - Rab32 and Rab38 genes in chordate pigmentation: an evolutionary perspective. AB - BACKGROUND: The regulation of cellular membrane trafficking in all eukaryotes is a very complex mechanism, mostly regulated by the Rab family proteins. Among all membrane-enclosed organelles, melanosomes are the cellular site for synthesis, storage and transport of melanin granules, making them an excellent model for studies on organelle biogenesis and motility. Specific Rab proteins, as Rab32 and Rab38, have been shown to play a key role in melanosome biogenesis. We analysed the Rab32 and Rab38 genes in the teleost zebrafish and in the cephalochordate amphioxus, gaining insight on their evolutionary history following gene and genome duplications. RESULTS: We studied the molecular evolution of Rab supergroup III in deuterostomes by phylogenetic reconstruction, intron and synteny conservation. We discovered a novel amino acid stretch, named FALK, shared by three related classes belonging to Rab supergroup III: Rab7L1, Rab32LO and Rab32/Rab38. Among these, we demonstrated that the Rab32LO class, already present in the last common eukaryotic ancestor, was lost in urochordates and vertebrates. Synteny shows that one zebrafish gene, Rab38a, which is expressed in pigmented cells, retained the linkage with tyrosinase, a protein essential for pigmentation. Moreover, the chromosomal linkage of Rab32 or Rab38 with a member of the glutamate receptor metabotropic (Grm) family has been retained in all analysed gnathostomes, suggesting a conserved microsynteny in the vertebrate ancestor. Expression patterns of Rab32 and Rab38 genes in zebrafish, and Rab32/38 in amphioxus, indicate their involvement in development of pigmented cells and notochord. CONCLUSIONS: Phylogenetic, intron conservation and synteny analyses point towards an evolutionary scenario based on a duplication of a single invertebrate Rab32/38 gene giving rise to vertebrate Rab32 and Rab38. The expression patterns of Rab38 paralogues highlight sub-functionalization event. Finally, the discovery of a chromosomal linkage between the Rab32 or Rab38 gene with a Grm opens new perspectives on possible conserved bystander gene regulation across the vertebrate evolution. PMID- 26818142 TI - Multi-modality Imaging: Bird's eye view from the 2015 American Heart Association Scientific Sessions. AB - Multiple novel studies were presented at the 2015 American Heart Association Scientific Sessions which was considered a successful conference at many levels. In this review, we will summarize key studies in nuclear cardiology, cardiac magnetic resonance, echocardiography, and cardiac computed tomography that were presented at the Sessions. We hope that this bird's eye view will keep readers updated on the newest imaging studies presented at the meeting whether or not they were able to attend the meeting. PMID- 26818143 TI - Myocardial blood flow from SPECT. PMID- 26818144 TI - Ventricular arrhythmias and autonomic nervous system: evolving role of radionuclide imaging. PMID- 26818145 TI - Equilibrium gated radionuclide angiocardiography: Its invention, rise, and decline and ... comeback? PMID- 26818146 TI - Professor Barrie Vernon-Roberts, AO, MD, BSc, PhD, FRCPath, FRCPA, FAOrthA (Hon), FRS.SA. PMID- 26818147 TI - Real-life experience with liver iron concentration R2 MRI measurement in patients with hemoglobinopathies: baseline data from LICNET. AB - BACKGROUND: Real-life data on the use of R2 MRI for the assessment of liver iron concentration (LIC) remain limited. METHODS: We conducted a cross-sectional analysis on 363 patients (mean age 35.6 yr, 44.1% men) with hemoglobinopathies (204 beta-thalassemia major [TM], 102 beta-thalassemia intermedia [TI], and 57 sickle cell disease [SCD]) that were evaluated with R2 MRI as part of LICNET, an MRI network of 13 Italian treatment centers. RESULTS: The mean LIC was 7.8 mg/g (median: 4.0), with high LIC (>7 mg/g) noted in both transfused (TM, TI 37%; SCD 38%) and non-transfused (TI 20%) patients. Ferritin levels correlated with LIC in both transfused (TM, TI, SCD) and non-transfused (TI) patients (P < 0.001), although lower values predicted high LIC in non-transfused patients (1900 vs. 650 ng/mL in TM vs. non-transfused TI). A correlation between LIC and ALT levels was only noted in HCV-negative patients (rs = 0.316, P < 0.001). The proportion of patients with high LIC was significantly different between iron chelators used (P = 0.023), with the lowest proportion in deferasirox (30%) and highest in deferiprone (53%)-treated patients. CONCLUSIONS: High LIC values persist in subgroups of patients with hemoglobinopathy, warranting closer monitoring and management optimization, even for non-transfused patients with relatively low ferritin levels. PMID- 26818148 TI - Association between sleeping difficulty and type 2 diabetes in women. AB - AIMS/HYPOTHESIS: Sleeping difficulty has been associated with type 2 diabetes in some prior studies. Whether the observed associations are independent of health behaviours, other cardiovascular risk factors or other sleep disorders is unclear. METHODS: We analysed data from 133,353 women without diabetes, cardiovascular disease and cancer at baseline in the Nurses' Health Study (NHS, 2000-2010) and the NHSII (2001-2011). Sleeping difficulty was assessed as having difficulty falling or staying asleep 'all of the time' or 'most of the time' at baseline (2000 in NHS and 2001 in NHSII). RESULTS: We documented 6,407 incident cases of type 2 diabetes during up to 10 years of follow-up. After adjustment for lifestyle factors at baseline, comparing women with and without sleeping difficulty, the multivariate-adjusted HR (95% CI) for type 2 diabetes was 1.45 (95% CI 1.33, 1.58), which changed to 1.22 (95% CI 1.12, 1.34) after further adjustment for hypertension, depression and BMI based on the updated repeated measurements. Women who reported all four sleep conditions (sleeping difficulty, frequent snoring, sleep duration <=6 h and sleep apnoea in NHS or rotating shift work in NHSII) had more than a fourfold increased likelihood of type 2 diabetes (HR 4.17, 95% CI 2.93, 5.91). CONCLUSIONS/INTERPRETATION: Sleeping difficulty was significantly associated with type 2 diabetes. This association was partially explained by associations with hypertension, BMI and depression symptoms, and was particularly strong when combined with other sleep disorders. Our findings highlight the importance of sleep disturbance in the development and prevention of type 2 diabetes. PMID- 26818149 TI - First-trimester multimarker prediction of gestational diabetes mellitus using targeted mass spectrometry. AB - AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is associated with an increased risk of pre-eclampsia, macrosomia and the future development of type 2 diabetes mellitus in both mother and child. Although an early and accurate prediction of GDM is needed to allow intervention and improve perinatal outcome, no single protein biomarker has yet proven useful for this purpose. In the present study, we hypothesised that multimarker panels of serum proteins can improve first-trimester prediction of GDM among obese and non-obese women compared with single markers. METHODS: A nested case-control study was performed on first-trimester serum samples from 199 GDM cases and 208 controls, each divided into an obese group (BMI >=27 kg/m(2)) and a non-obese group (BMI <27 kg/m(2)). Based on their biological relevance to GDM or type 2 diabetes mellitus or on their previously reported potential as biomarkers for these diseases, a number of proteins were selected for targeted nano-flow liquid chromatography (LC) MS analysis. This resulted in the development and validation of a 25-plex multiple reaction monitoring (MRM) MS assay. RESULTS: After false discovery rate correction, six proteins remained significantly different (p<0.05) between obese GDM patients (n=135) and BMI-matched controls (n=139). These included adiponectin, apolipoprotein M and apolipoprotein D. Multimarker models combining protein levels and clinical data were then constructed and evaluated by receiver operating characteristic (ROC) analysis. For the obese, non-obese and all GDM groups, these models achieved marginally higher AUCs compared with adiponectin alone. CONCLUSIONS/INTERPRETATION: Multimarker models combining protein markers and clinical data have the potential to predict women at a high risk of developing GDM. PMID- 26818150 TI - Influence of Step Rate on Shin Injury and Anterior Knee Pain in High School Runners. AB - PURPOSE: High school cross-country runners have a high incidence of injury, particularly at the shin and knee. An increased step rate during running has been shown to reduce impact forces and loading of the lower extremity joints. The purpose of this prospective study was to examine step rate as a risk factor for injury occurrence. MATERIALS AND METHODS: Running step rates of 68 healthy high school cross-country runners (47 females; 21 males; mean age 16.2 +/- 1.3 yr) were assessed at a fixed speed (3.3 +/- 0.0 m.s) and self-selected speed (mean, 3.8 +/- 0.5 m.s). Runners were prospectively followed during the interscholastic season to determine athletic exposures, occurrences of shin injury and anterior knee pain (AKP), and days lost to injury. RESULTS: During the season, 19.1% of runners experienced a shin injury and 4.4% experienced AKP. Most injuries (63.6%) were classified as minor (1-7 d lost). At the fixed speed, runners in the lowest tertile of step rate (<=164 steps per minute) were more likely (odds ratio, 6.67; 95% confidence interval, 1.2-36.7; P = 0.03) to experience a shin injury compared with runners in the highest tertile (>=174 steps per minute). Similarly, for self selected speed, runners in the lowest tertile (<=166 steps per minute) (odds ratio, 5.85; 95% confidence interval, 1.1-32.1; P < 0.04) were more likely to experience a shin injury than runners in the highest tertile (>=178 steps per minute). AKP incidence was not significantly influenced by step rate. CONCLUSION: A lower running step rate was associated with a greater likelihood of shin injury at both self-selected and fixed running speeds. Future studies evaluating whether increasing running step rate reduces shin injury risk and time lost during a high school cross-country season should be considered. PMID- 26818152 TI - Admission serum lactate predicts mortality in aneurysmal subarachnoid hemorrhage. AB - BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) is the most devastating form of hemorrhagic stroke. Primary predictors of mortality are based on initial clinical presentation. Initial serum lactic acid levels have been shown to predict mortality and disease severity. Initial serum lactate may be an objective predictor or mortality. METHODS: Retrospective review of aneurysmal SAH in a large academic center over a 42-month period. Data collected included demographics, clinical data, serum, and clinical outcomes data. Epidemiologic data were collected at baseline, and patients were followed up through their inpatient stay. We compared data in the group of patients who were deceased (group A) vs survivors (group B). RESULTS: There were a total of 249 patients. Mortality was 21.5%. Mean age was the same for both groups: 57 years (group A) and 55 years (group B). Mean admission serum lactate level was 3.5 +/- 2.5 (group A) and 2.2 +/- 1.6 (group B; P <. 0001). The range was 0.01 to 14.7. Multivariable analysis controlling for Hunt and Hess grades showed lactic acid levels to be an independent predictor of mortality with a P value of .0018. CONCLUSIONS: In aneurysmal SAH, elevated serum lactate levels on admission may have a predictive role for mortality and represent a marker of disease severity. Currently, lactic acid levels are not ordered on all patients with SAH but perhaps should be part of the routine initial blood work and may serve as an additional prognostic marker. PMID- 26818151 TI - Progesterone modulates endothelial progenitor cell (EPC) viability through the CXCL12/CXCR4/PI3K/Akt signalling pathway. AB - OBJECTIVES: Progesterone treatment can effectively increase levels of circulating endothelial progenitor cells (EPCs) and improve neurological functional outcome in a traumatic brain injury (TBI) rat model. However, the mechanisms of progesterone's effects on EPC viability remain elusive. The CXCL12/CXCR4 (CXC chemokine ligand 12/CXC chemokine receptor 4) signalling pathway regulates cell proliferation; we hypothesize that it mediates progesterone-induced EPC viability. MATERIALS AND METHODS: EPCs were isolated from bone marrow-derived mononuclear cells (BM-MNCs) and treated with progesterone (5, 10 and 100 nm). MTS assay was used to investigate EPC viability. Protein expression was examined by Western blotting, ELISA assay and flow cytometry. Cell membrane and cytoplasm proteins were extracted with membrane and cytoplasm protein extraction kits. CXCR4 antagonist (AMD3100) and phosphatidylinositol 3-kinases (PI3K) antagonist (LY294002) were used to characterize underlying mechanisms. RESULTS: Progesterone induced EPC viability was time- and dose-dependent. Administration of progesterone facilitated EPC viability and increased expression of CXCL12 and phosphorylated Akt (also known as protein kinase B, pAkt) activity (P < 0.05). Progesterone did not regulate CXCR4 protein expression in cultured EPC membranes or cytoplasm. However, progesterone-induced EPC viability was significantly attenuated by AMD3100 or LY294002. Inhibition of the signalling pathway with AMD3100 and LY294002 subsequently reduced progesterone-induced CXCL12/CXCR4/PI3K/pAkt signalling activity. CONCLUSIONS: The CXCL12/CXCR4/PI3K/pAkt signalling pathway increased progesterone-induced EPC viability. PMID- 26818153 TI - The relation between signal peptide-CUB-EGF domain-containing protein 1 and coronary artery disease. PMID- 26818154 TI - Brugada electrocardiogram pattern induced by cannabis; is cannabis safe? PMID- 26818155 TI - Paramedic assessment and treatment of upper airway obstruction in pediatric patients: an exploratory analysis by the Children's Safety Initiative-Emergency Medical Services. PMID- 26818156 TI - A case of the cerebellar cognitive affective syndrome in a 12-year-old boy with acute post-infectious cerebellar ataxia. AB - BACKGROUND: The cerebellar cognitive affective syndrome (CCAS), is characterised by disturbances in executive functions, visuospatial difficulties, personality changes, and linguistic difficulties. It is well described in other diseases of the cerebellum such as tumour resection and cerebellar stroke but has not previously been described in detail in paediatric cases of acute post-infectious ataxia (APCA). METHODS: Case study. A 12-year-old boy was admitted with severe ataxia, dysmetria, dysdiadokinesia, and dysarthria. He was diagnosed with acute post-infectious cerebellar ataxia (APCA). Besides motor symptoms, the patient showed signs of disturbances in executive functions, visiospatial difficulties, personality changes, and linguistic difficulties. These symptoms correspond to CCAS. CONCLUSION: CCAS may be an overlooked complication to APCA. In addition, APCA is considered a transient, monophasic disease and studying CCAS in this disease may give insight into subtle cases of CCAS and thus provide new knowledge about CCAS. PMID- 26818157 TI - PLCB1 epileptic encephalopathies; Review and expansion of the phenotypic spectrum. AB - BACKGROUND: Biallelic loss-of-function mutations of phospholipase C-beta1 (PLCB1) have been described in three children with an early onset epileptic encephalopathy (EE). In two of them a homozygous deletion of the promotor and first three coding exons was found. The third patient had an almost identical heterozygous deletion in combination with a heterozygous splice site variant. All patients had intractable epilepsy and a severe developmental delay. METHODS AND RESULTS: We present the case of a boy with an infantile EE starting at the age of four months with a fever induced status epilepticus, modified hypsarrhythmia and developmental regression. The epilepsy was reasonably controlled with corticoids and valproate whereupon generalized tonic-clonic seizures appeared only each 3-4 months. However, only a slow developmental progress was seen hereafter, resulting in a severe intellectual disability with absent speech, motor delay and autistic features. We identified a novel homozygous partial deletion of PLCB1, affecting exons 7-9. CONCLUSIONS: This report emphasizes the role of PLCB1 haploinsufficiency in severe EE. We demonstrate a phenotypic variability in patients with a PLCB1-associated EE. In addition, our findings underscore the importance of microarray analysis in all patients with an EE of unknown etiology. PMID- 26818158 TI - Cerebral venous sinus thrombosis in a patient with Cushings syndrome due to topical steroid. PMID- 26818159 TI - Editorial Message. PMID- 26818160 TI - The use of immune modulating drugs for the treatment of multiple sclerosis. AB - This review discusses the mechanisms of action of 4 immune modulating drugs currently used in the treatment of multiple sclerosis (MS), including Alemtuzumab, a humanized monoclonal antibody that functions by targeting CD52, an antigen primarily expressed on T and B lymphocytes and monocytes/macrophages, resulting in their depletion and subsequent repopulation; Dimethyl fumarate that switches cytokine production toward a T helper 2 profile and enhances cytosolic levels of nuclear factor erythroid 2-related factor 2, which has immune regulatory and cytoprotective effects on oligodendrocytes, neurons, and glial cells; Fingolimod functions by blocking the release of activated lymphocytes from lymph nodes by targeting sphingosin-1-phosphate receptors; Natalizumab a humanized monoclonal antibody binds alpha4beta1-integrin resulting in reduced migration of immune cells from blood across the blood-brain barrier into the CNS. This review presents the most up to date information on mechanisms of action, safety, and efficacy of these immune modulators and provides future perspectives for the treatment of MS. PMID- 26818161 TI - Impact of operation details on hydrocephalus after decompressive craniectomy. AB - OBJECTIVE: To evaluate the correlation between the distance of craniectomy from the midline and hydrocephalus after DC. METHODS: The following electronic databases were searched from their inception to June 2015: Cochrane Library, MEDLINE, Science Direct, EMBASE, Scopus, Google Scholar, the Chinese Biomedical Database (CBM), and the Chinese National Knowledge Infrastructure (CNKI). All randomized clinical trials, prospective cohort, retrospective observational cohort, and case-control studies investigating the relationship between distance of craniectomy from the midline and hydrocephalus after DC were enrolled. The Cochrane Collaborations software RevMan 5.3 was used for meta-analysis. RESULTS: Six retrospective cohort studies involving 462 participants were included. Pooled analysis of 4 studies suggested that craniectomy close to the midline (<25 mm) was associated with a significantly increased risk of postoperative hydrocephalus (odds ratio [OR] = 3.61, 95% confidence interval [CI]: 1.3 - 9.97, p=0.01). However, meta analysis of 4 studies did not find statistical differences when comparing the distance of craniectomy from the midline in the hydrocephalus group and that in the non-hydrocephalus group (OR= - 0.14, 95% CI: -0.44 - 0.15, p=0.34). CONCLUSION: Available evidence was insufficient to support the theory that craniectomy close to the midline increases the risk of developing hydrocephalus after DC. Well conducted randomized clinical trials are required to verify this issue. PMID- 26818162 TI - The use of magnetically controlled growing rod device for pediatric scoliosis. AB - OBJECTIVE: To study the safety and efficacy of an innovative device using distraction-based magnetically controlled growing rods (MCGR) for the treatment of pediatric scoliosis. METHODS: This is an evidence-based systematic review of literature for the surgical management of patients with pediatric scoliosis using MCGR technique. Six clinical studies regarding the use of MCGR were included in this review, with a total of 68 patients, and mean age of 8.38 years. The dual rod (DR) technique of rod construct with MCGR was used in 33.85% and the single rod (SR) in 66.15% of the patients. RESULTS: The mean preoperative main coronal curve for the DR was 65.9 degrees , and for the SR was 69.6 degrees (p>0.05). At the latest follow-up, it was 36.8 degrees for DR and 43.0 degrees for SR (p<0.05). The mean preoperative T1 - S1 spinal length was 298.7 mm for the DR and 303.5 mm for the SR group (p<0.05). According to the latest follow-up, using the DR construct, the spinal length increased to 347 mm with 13.92% of total lengthening; and using the SR construct, the average lengthening was 339 mm, with 10.48% of total lengthening (p<0.05). Postoperative complications were similar, 25% in DR and 31.57% in the SR group (p>0.05). CONCLUSION: Level IV of medical evidence supports the use of MCGR as a safe and effective alternative for the treatment of severe pediatric scoliosis. Recommendation Grade C supports the role of MCGR with DR construct as an option to achieve a better correction of the scoliotic curve and to maximize the postoperative T1 - S1 spinal length. PMID- 26818163 TI - Electrophysiological assessment in patients with long term hypoxia. AB - OBJECTIVE: To evaluate visual evoked potentials (VEP) patterns in chronic obstructive pulmonary disease (COPD) patients who were compliant with supplemental oxygen treatment relative to non-compliant COPD patients. METHODS: This prospective study protocol was reviewed and approved by the local ethical committee of Selcuk University and the research was performed in the Department of Neurology, Elbistan State Hospital, Kahramanmaras, Turkey from May to October 2014. Blood gas measurements and pulmonary function tests were carried out in patients with advanced stage COPD. The VEP was assessed in both eyes in both compliant and non-compliant patients. RESULTS: The study included 43 patients; 24 (55.8%) of the patients were not in compliance with their supplemental oxygen treatment, while 19 patients (44.2%) received adequate oxygen treatment. There was no statistically significant difference between patients with regards to pulmonary function test results and blood gas measurements. The VEP latency was significantly greater in both eyes of the non-compliant patients. CONCLUSION: Previous studies have reported prolonged VEP latencies in inflammatory diseases of the central nervous system. Similar electrophysiological findings were observed in our study and we propose that this may be due to oxidative stress, and inflammation that occurs secondary to chronic ischemia. PMID- 26818164 TI - Alternatives to surgical approach for giant spinal schwannomas. AB - OBJECTIVE: To review the diagnoses and surgical approach characteristics of giant spinal schwannomas (GSS) patients. METHODS: We reviewed the preoperative and postoperative radiological and clinical data, and the surgical aspects of 18 GSS patients who underwent surgery in the Department of Neurosurgery, Umraniye Teaching Hospital and Research State Hospital, Istanbul, Turkey between January 2008 and December 2013. RESULTS: There were 15 (83.3%) female and 3 (16.6%) male patients. The age range was 16-70 years (average: 45.8). Average symptom duration was 1.5 months (range: 1-48). There was local pain in 15 cases, and radicular pain in 6 cases. The GSSs were most frequently located in the lumbosacral area (11 cases, 61.1%). An extraforaminal surgical approach was employed in 7 cases, a posterior approach was employed in 6 cases, a combined anterior transabdominal and posterior approach was employed in 2 cases, a combined posterior and extraforaminal approach was employed in 2 cases, and a retroperitoneal approach was applied in one case. The tumors were completely excised in all cases. The mean follow-up period was 38.5 months (range: 20-68). CONCLUSION: Giant spinal schwannomas exhibit unique diagnostic and surgical factors. The selection of an appropriate approach significantly influences the success of the treatment. PMID- 26818165 TI - Psychiatric patients awareness of their illnesses and medications. AB - OBJECTIVE: To assess awareness of Saudi psychiatric patients of their illnesses and medications at Prince Sultan Military Medical City (PSMMC). METHODS: A cross sectional study was conducted at the outpatients clinics of PSMMC, Riyadh, Kingdom of Saudi Arabia from January to December 2012. The study included 647 patients undergoing treatment for their psychiatric illnesses. The patients were interviewed using a structured questionnaire. RESULTS: Most of the adult patients 555 (86.6%) had enough awareness of their diagnosis (58.2%); however, it was insignificant compared with other groups. The adult group (n=301, 87.2%) had more medication knowledge than the younger group (55.8%). Gender association with diagnosis (p>==0.058) and medications (p>==0.094) was not quite significant. In education, most of the patients were illiterate, next were secondary school, elementary graduates, intermediate, and university graduated. Most of illiterate and elementary graduates were unaware of both diagnosis and medications, while higher education reflected better diagnosis and medications knowledge, with extreme significance (p<0.000). Illness duration showed a majority in awareness for those with longer periods of illness. Admission times reflected extreme significance (p<0.000) of both levels of awareness. Patient illnesses also showed extreme significance (p=0.000 and p=0.002) of both awareness levels. CONCLUSION: Although lack of awareness is common, in this study most patients were aware of their diagnosis and medications. Less than half of the patients could neither specify their illnesses nor their medications, which could be attributed to the limited information provided. PMID- 26818166 TI - Incidence of autism in high risk neonatal follow up. AB - OBJECTIVE: To detect autism spectrum disorder (ASD) cases within the High Risk Neonatal Follow up Program (HRNFP), as an indicator of the prevalence of ASD and associated risk factors in the Kingdom of Saudi Arabia (KSA). METHODS: We conducted this retrospective medical chart review in a tertiary care hospital in Riyadh, KSA. All patients admitted to the HRNFP were seen at 3 years corrected age between January 2012 and December 2013. Patients diagnosed with ASD from the HRNFP were referred to the King Fahad Medical City (KFMC) Autism Program for further assessment. The following potential risk factors for ASD were documented: low birth weight, gestational age less than 33 weeks, and male gender. RESULTS: In 2012, 59 patients were evaluated in the HRNFP. Three cases were diagnosed with ASD, with an ASD incidence rate of 5.1% (95% confidence interval [CI] calculated by adjusted Wald method: 1.2-14.5%). In 2013, 48 patients were evaluated and 2 cases were diagnosed with ASD, with an ASD incidence rate of 4.2% (95% CI: 0.4% 14.8%). The total ASD incidence rate during the 2-year study period was 4.7% (95% CI: 1.7%-10.8%). Factors associated with a higher likelihood of ASD were: male gender, low birth weight, and gestational age less than 33 weeks. CONCLUSION: Compared with the community, the prevalence of ASD was higher in the HRNFP. Further investigation is required to evaluate risk factors. PMID- 26818167 TI - Health related quality of life in patients admitted for video electroencephalography monitoring diagnosed with epilepsy or psychogenic non epileptic seizures. AB - OBJECTIVE: To determine the health related quality of life (HRQOL) in patients with epilepsy or psychogenic non-epileptic seizures (PNES). METHODS: This cross sectional study was carried out between December 2010 and December 2014 in the Department of Neurology and Psychiatry, Faculty of Medicine, Baskent University, Adana, Turkey. Patients who were admitted for video-electroencephalography monitoring and diagnosed of epileptic seizures or PNES were asked to complete a questionnaire from the World Health Organization Quality of Life, and psychiatric comorbidities were diagnosed using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders Fourth Edition. RESULTS: Patients with epilepsy and PNES were found to have similar HRQOL in physical, psychological, social, and environmental domains. However, the percentage of comorbid psychiatric disorders were higher in patients with PNES than patients with epilepsy. CONCLUSION: Patients with epilepsy and PNES have similar HRQOL, and PNES are resistant to the standard medical therapies used for the treatment of epileptic seizures. The direct lifetime cost of undiagnosed PNES may be of equal with intractable epilepsy. A better understanding of the impact of PNES manifestations and epilepsy would help to provide appropriate clinical, psychological and social care. PMID- 26818168 TI - Idiopathic intracranial hypertension presenting as postpartum headache. AB - Postpartum headache is described as headache and neck or shoulder pain during the first 6 weeks after delivery. Common causes of headache in the puerperium are migraine headache and tension headache; other causes include pre eclampsia/eclampsia, post-dural puncture headache, cortical vein thrombosis, subarachnoid hemorrhage, posterior reversible leukoencephalopathy syndrome, brain tumor, cerebral ischemia, meningitis, and so forth. Idiopathic intracranial hypertension (IIH) is a rare cause of postpartum headache. It is usually associated with papilledema, headache, and elevated intracranial pressure without any focal neurologic abnormality in an otherwise healthy person. It is more commonly seen in obese women of reproductive age group, but rare during pregnancy and postpartum. We present a case of IIH who presented to us 18 days after cesarean section with severe headache and was successfully managed. PMID- 26818169 TI - Hemichorea with unilateral MRI striatal hyperintensity in a Saudi patient with diabetes. AB - Hemichorea is a disorder characterized by abnormal, continuous, nonrhythmic, jerky, and distal movement involving one side of the body. It may result from cerebrovascular insult to basal ganglia, or from other causes including neoplasm, infection, and non-ketotic hyperglycemia. We report the clinical, laboratory, and neuroimaging data with treatment response of a Saudi woman who has diabetes with left side hemichorea, involving the face, and upper and lower extremities, with unilateral right striatal hyperintense signal changes in T1 weighted MRI, and a hyperglycemic state of longstanding uncontrolled diabetes. Literature review suggested a syndrome with a triad of symptoms: non-ketotic hyperglycemia, hemichorea, and T1 MRI striatal hyperintensities. As the number of internationally reported cases is still modest, reporting more patients will highlight aspects pertaining to the diagnosis and treatment of this condition. We present a patient who had a sustained therapeutic result from haloperidol and clonazepam. PMID- 26818170 TI - Traumatic intracranial internal carotid artery pseudoaneurysm presenting as epistaxis treated by endovascular coiling. AB - Traumatic intracranial pseudoaneurysm is a rare complication of blunt trauma. It is even more rare when it presents as epistaxis. Massive epistaxis of a ruptured intracranial internal carotid artery pseudoaneurysm is a major cause of mortality, which requires emergency intervention. We report a case of traumatic intracranial internal carotid artery pseudoaneurysm secondary to skull base fracture, which presented with delayed onset of epistaxis. This was successfully treated by primary endovascular coil embolization. We discuss endovascular treatment options and review the literature. PMID- 26818171 TI - The relationship between emotional intelligence and task-switching in temporal lobe epilepsy. AB - OBJECTIVE: To examine the role of emotional intelligence (EI) in task-switching performance of patients with temporal lobe epilepsy (TLE). METHODS: An experimental research design conducted at Sheikh Zayed Hospital, Rahim Yar Khan, Mayo and Services Hospital, Lahore, Pakistan from March 2013 to October 2014. Twenty-five patients with TLE and 25 healthy individuals from local community participated in the study. Participants completed measures of intelligence, EI, depression, anxiety, stress, and task-switching experiment. RESULTS: Patients and controls showed an average intelligence quotient, and normal levels of depression, anxiety, and stress. In contrast to controls, patients showed lower EI and impaired task-switching abilities. This result can be seen in the context of disintegrated white matter and cerebral connectivity in patients with TLE. Emotional intelligence was found to be a significant predictor of task-switching performance. CONCLUSION: Emotional intelligence is a potential marker of higher order cognitive functioning in patients with TLE. PMID- 26818172 TI - Percutaneous endoscopic gastrostomy versus nasogastric tube feeding during neurorehabilitation. Ifs, ands, or buts. PMID- 26818173 TI - Chromosome 6 microdeletion in a patient with syndromic congenital cranial dysinnervation disorder. PMID- 26818174 TI - Response to rituximab in an anti-muscle-specific receptor tyrosine kinase- and anti-acetylcholine recepto-double-positive myasthenia gravis patient concomitant with follicular dendritic cell sarcoma. PMID- 26818175 TI - De Novo intracerebral aneurysm in a child with acquired immunodeficiency syndrome. PMID- 26818176 TI - Genetically engineered mouse models to evaluate the role of Wnt secretion in bone development and homeostasis. AB - Alterations in components of the Wnt signaling pathway are associated with altered bone development and homeostasis in several human diseases. We created genetically engineered mouse models (GEMMs) that mimic the cellular defect associated with the Porcupine mutations in patients with Goltz Syndrome/Focal Dermal Hypoplasia. These GEMMs were established by utilizing mice containing a conditionally inactivatable allele of Wntless/GPR177 (a gene encoding a protein required for the transport of Porcupine-modified ligand to the plasma membrane for secretion). We crossed this strain to another which drives cre-mediated gene deletion in mature osteoblasts (Osteocalcin-cre) resulted in mice lacking the ability to secrete Wnt ligands in this cell type. These mice displayed severely reduced bone mass and provide a model to understand the effects of disrupting the ability to secrete Wnt ligands on the skeletal system. PMID- 26818178 TI - Oscillatory control of Delta-like1 in somitogenesis and neurogenesis: A unified model for different oscillatory dynamics. AB - During somite segmentation, mRNA expression of the mouse Notch ligand Delta-like1 (Dll1) oscillates synchronously in the presomitic mesoderm (PSM). However, the dynamics of Dll1 protein expression were rather controversial, and their functional significance was not known. Recent live-imaging analysis showed that Dll1 protein expression also oscillates synchronously in the PSM. Interestingly, accelerated or delayed Dll1 expression by shortening or elongating the Dll1 gene, respectively, dampens or quenches Dll1 oscillation at intermediate levels, a phenomenon known as "amplitude/oscillation death" of coupled oscillators in mathematical modeling. Under this condition, oscillation of the Notch effector Hes7 is also dampened, leading to severe fusion of somites and their derivatives, such as vertebrae and ribs. Thus, the appropriate timing of Dll1 expression is critical for its oscillatory expression, pointing to the functional significance of Dll1-mediated oscillatory cell-cell interactions in the segmentation clock. In neural stem cells, Dll1 expression is also oscillatory, but non-synchronous, and when Dll1 oscillation is dampened, oscillation of another Notch effector, Hes1, is also dampened, leading to defects of neural development. In this review, we discuss the underlying mechanism for the different oscillatory dynamics (synchronous versus non-synchronous) in the PSM and neural stem cells in a unified manner. PMID- 26818177 TI - Studies on human eRF3-PABP interaction reveal the influence of eRF3a N-terminal glycin repeat on eRF3-PABP binding affinity and the lower affinity of eRF3a 12 GGC allele involved in cancer susceptibility. AB - The eukaryotic release factor 3 (eRF3) has been involved in the control of mRNA degradation through its association with the cytoplasmic Poly(A) Binding Protein, PABP. In mammals, eRF3 N-terminal domain contains two overlapping PAM2 motifs which specifically recognize the MLLE domain of PABP. In humans, eRF3a/GSPT1 gene contains a stable GGC repeat encoding a repeat of glycine residues in eRF3a N terminus. There are five known eRF3a/GSPT1 alleles in the human population, encoding 7, 9, 10, 11 and 12 glycines. Several studies have reported that the presence of eRF3a 12-GGC allele is correlated with an increased risk of cancer development. Using surface plasmon resonance, we have studied the interaction of the various allelic forms of eRF3a with PABP alone or poly(A)-bound PABP. We found that the N-terminal glycine repeat of eRF3a influences eRF3a-PABP interaction and that eRF3a 12-GGC allele has a decreased binding affinity for PABP. Our comparative analysis on eRF3a alleles suggests that the presence of eRF3a 12-GGC allele could modify the coupling between translation termination and mRNA deadenylation. PMID- 26818179 TI - Comparative in vivo toxicity assessment places multiwalled carbon nanotubes at a higher level than mesoporous silica nanoparticles. AB - In the present work, we took two nanomaterials (NMs), mesoporous silica nanoparticles (MSNs) and multiwalled carbon nanotubes (MWCNTs), and compared their in vivo toxicity taking albino mice as a test animal model. Presently, conflicting data persist regarding behavior of these NMs with macromolecules like protein and lipid at the cellular level in cell lines as well as in animal models and this generated the interest to study them. The mice were treated orally with a single dose of 50 ppm MWCNTs and intraperitoneally with 10, 25, and 50 mg kg-1 body weight (BW) of MSNs and 1.5, 2.0, and 2.5 mg kg-1 BW of MWCNTs. Liver enzyme markers serum aspartate aminotransferase (AST), alanine aminotransferase, and alkaline phosphatase along with total protein (TP) levels were evaluated 7 days postexposure. No significant differences in organ weight indices or enzyme levels were observed between different treatment doses but there were significant differences between the treatment groups and the controls. Of the three enzymes assayed, AST displayed a peculiar pattern, especially in the MWCNTs intraperitoneally treated group. TP level was significantly increased in the orally treated MWCNTs group. The results showed that MWCNTs even at much smaller doses than MSNs displayed similar toxicity levels, suggesting that toxicity of MWCNTs is greater than MSNs. PMID- 26818180 TI - Determinants of iron status and Hb in the Bangladesh population: the role of groundwater iron. AB - OBJECTIVE: Using data from the national micronutrients survey 2011-2012, the present study explored the determinants of Fe status and Hb levels in Bangladesh with a particular focus on groundwater Fe. DESIGN: Cross-sectional study conducted at the nationwide scale. Settings The survey was conducted in 150 clusters, fifty in each of the three strata of rural, urban and slum. SUBJECTS: Three population groups: pre-school age children (6-59 months; PSAC), school age children (6-14 years; SAC) and non-pregnant non-lactating women (15-49 years; NPNLW). RESULTS: National prevalence of Fe deficiency was 10.7 %, 7.1 % and 3.9 9.5 % in PSAC, NPNLW and SAC, respectively. Prevalence of anaemia was 33.1 % (PSAC), 26.0 % (NPNLW) and 17.1-19.1 % (SAC). Multivariate regression analyses showed that the area with 'predominantly high groundwater Fe' was a determinant of higher serum ferritin levels in NPNLW (standardized beta=0.19; P=0.03), SAC (standardized beta=0.22; P=0.01) and PSAC (standardized beta=0.20; P=0.03). This area also determined higher levels of Hb in PSAC (standardized beta=0.14; P=0.01). CONCLUSIONS: National prevalence of Fe deficiency in Bangladesh is low, contrary to the widely held assumption. High Fe level in groundwater is associated with higher Fe status (all populations) and higher Hb level (PSAC). PMID- 26818181 TI - Rational design of hierarchical ZnO superstructures for efficient charge transfer: mechanistic and photovoltaic studies of hollow, mesoporous, cage-like nanostructures with compacted 1D building blocks. AB - Mesoporous and hollow zinc oxide (ZnO) hierarchical superstructures assembled with compact 1D building blocks that provide an efficient and faster transport pathway for photo-generated charge carriers have been synthesized using a biomass derived polysaccharide "alginic acid". To understand the interactions between the organic bio-template and inorganic growth units of ZnO in aqueous medium, the effects of additives such as the alginate ion (ALGI) and ammonium hydroxide (NH4OH), along with the controlled reaction conditions, are investigated using Field Emission Scanning Electron Microscopy (FESEM) and powder X-ray diffraction. Dynamic and steady-state photoluminescence measurements are carried out to understand the charge transfer processes in the compact 1D superstructures. Experimental analyses reveal that the alginate ions, under hydrothermal reaction conditions, act as a structure directing agent and assemble 1D ZnO nanorods (NRs) hierarchically while NH4OH assists the formation of ZnO growth units. A plausible mechanism for ZnO cage formation is proposed based on the experimental observations. Morphology dependent photovoltaic properties of ZnO heterostructures, i.e., for ZnO cages, ZnO NRs and ZnO PNPs, have been studied along with electrochemical impedance spectroscopy (EIS). Enhancement of ~ 60% and ~ 35% in power conversion efficiency (PCE) is observed in ZnO cage based devices as compared to ZnO NR- and ZnO PNP-based devices, respectively. PMID- 26818182 TI - Prospective analysis of the flows of certain rare earths in Europe at the 2020 horizon. AB - This paper proposes a forecast of certain rare earth flows in Europe at the 2020 horizon, based on an analysis of trends influencing various actors of the rare earth industry along the value chain. While 2020 is indicated as the forecast horizon, the analysis should be considered as more representative of the next decade. The rare earths considered here are used in applications that are important for a low-carbon energy transition and/or have a significant recycling potential: NdFeB magnets (Pr, Nd, Dy), NiMH batteries (Pr, Nd) and fluorescent lamp phosphors (Eu, Tb, Y). An analysis of major trends affecting the rare earth industry in Europe along the value chain (including extraction, separation, fabrication, manufacture, use and recycling), helps to build a scenario for a material flow analysis of these rare earths in Europe. The scenario assumes in particular that during the next decade, there exists a rare earth mine in production in Europe (with Norra Karr in Sweden as a most likely candidate) and also that recycling is in line with targets proposed in recent European legislation. Results are presented in the form of Sankey diagrams which help visualize the various flows for the three applications. For example, calculations forecast flows from extraction to separation of Pr, Nd and Dy for magnet applications in Europe, on the order of 310 tons, 980 tons and 80 tons rare earth metal resp., while recycled flows are 35 tons, 110 tons and 30 tons resp. Calculations illustrate how the relative contribution of recycling to supply strongly depends on the situation with respect to demand. Considering the balance between supply and demand, it is not anticipated any significant shortage of rare earth supply in Europe at the 2020 horizon, barring any new geopolitical crisis involving China. For some heavy rare earths, supply will in fact largely outweigh demand, as for example Europium due to the phasing out of fluorescent lights by LEDs. PMID- 26818183 TI - Adsorption of methylene blue on biochar microparticles derived from different waste materials. AB - Biochar microparticles were prepared from three different types of biochar, derived from waste materials, such as pine wood (BC-PW), pig manure (BC-PM) and cardboard (BC-PD) under various pyrolysis conditions. The microparticles were prepared by dry grinding and sequential sieving through various ASTM sieves. Particle size and specific surface area were analyzed using laser particle size analyzer. The particles were further characterized using scanning electron microscope (SEM). The adsorption capacity of each class of adsorbent was determined by methylene blue adsorption tests in comparison with commercially available activated carbon. Experimental results showed that dye adsorption increased with initial concentration of the adsorbate and biochar dosage. Biochar microparticles prepared from different sources exhibited improvement in adsorption capacity (7.8+/-0.5 mg g(-1) to 25+/-1.3 mg g(-1)) in comparison with raw biochar and commercially available activated carbon. The adsorption capacity varied with source material and method of production of biochar. The maximum adsorption capacity was 25 mg g(-1) for BC-PM microparticles at 25 degrees C for an adsorbate concentration of 500 mg L(-1) in comparison with 48.30+/-3.6 mg g( 1) for activated carbon. The equilibrium adsorption data were best described by Langmuir model for BC-PM and BC-PD and Freundlich model for BC-PW. PMID- 26818184 TI - Methane from CO2: Influence of different CO2 concentrations in the flush gas on the methane production in BMP tests. AB - The influence of carbon dioxide (CO2) in the headspace gas on the specific methane (CH4) production of blank samples with just inoculum during Biochemical Methane Potential (BMP) tests was studied. The headspace of the bottles had been flushed with 15 different ratios of CO2 and N2 prior to incubation, while they were treated otherwise identically. The results revealed that the CH4 yield increased linearly with higher ratio of CO2 in the flush gas reaching a 30% higher yield at pure CO2 relative to pure N2 headspace conditions. However, a slightly distinct lag is noticeable during the initial phase of the degradation process at high ratios of CO2, hypothesizing a reversible disturbance of the biocenosis. Further experiments and analyses need to be performed to elucidate the underlying mechanisms. PMID- 26818185 TI - Small-Angle Neutron Scattering Studies on the Multilamellae Formed by Mixing Lamella-Forming Cationic Diblock Copolymers with Lipids and Their Interaction with DNA. AB - We demonstrate that the lamella-forming polystyrene-block-poly(N-methyl-4 vinylpyridinium iodine) (PS-b-P4VPQ), with similar sizes of the PS and P4VPQ blocks, can be dispersed in the aqueous solutions by forming lipid/PS-b-P4VPQ multilamellae. Using small-angle neutron scattering (SANS) and 1,2-dipalmitoyl d62-sn-glycero-3-phosphocholine (d62-DPPC) in D2O, a broad correlation peak is found in the scattering profile that signifies the formation of the loosely ordered d62-DPPC/PS-b-P4VPQ multilamellae. The thicknesses of the hydrophobic and hydrophilic layers of the d62-DPPC/PS-b-P4VPQ multilamellae are close to the PS layer and the condensed brush layer thicknesses as determined from previous neutron reflectometry studies on the PS-b-P4VPQ monolayer at the air-water interface. Such well-dispersed d62-DPPC/PS-b-P4VPQ multilamellae are capable of forming multilamellae with DNA in aqueous solution. It is found that the encapsulation of DNA in the hydrophilic layer of the d62-DPPC/PS-b-P4VPQ multilamellae slightly increases the thickness of the hydrophilic layer. Adding CaCl2 can enhance the DNA adsorption in the hydrophilic brush layer, and it is similar to that observed in the neutron reflectometry study of the DNA adsorption by the PS-b-P4VPQ monolayer. PMID- 26818186 TI - Serum albumin is an early predictor of complications after liver surgery. AB - BACKGROUND: The morbidity associated with liver surgery remained substantially high despite considerable surgical and anesthetic improvements. The unmet need of accurate biomarkers to predict postoperative complications is widely accepted. AIMS: This pilot study aimed to assess serum albumin as a surrogate marker of surgical stress and to test its potential predictive role for postoperative complications. METHODS: This retrospective pilot study included 106 patients who underwent liver surgery between 2010 and 2014. Serum albumin levels were measured pre- and post-operatively. Maximal albumin decrease (AlbDeltamin) was correlated with complications. RESULTS: Serum albumin rapidly dropped after surgery. AlbDeltamin was significantly increased in patients with complications (14.5+/ 6.0g/L vs. 10.3+/-7.2, p=0.009). On multivariate analysis, ASA III/IV (p=0.016) and AlbDeltamin (p=0.037) were the only predictors of overall complications. CONCLUSION: Early postoperative drop of serum albumin reflects the intensity of the surgical stress and may predict complications after liver surgery. Serum albumin is a biomarker displaying precious features and deserving further prospective investigations. PMID- 26818187 TI - NMR reveals the surface functionalisation of Ti3C2 MXene. AB - (1)H and (19)F NMR experiments have identified and quantified the internal surface terminations of Ti3C2Tx MXene. -F and -OH terminations are shown to be intimately mixed and there are found to be significantly fewer -OH terminations than -F and -O, with the proportions highly dependent on the synthesis method. PMID- 26818189 TI - Biomonitoring of the environmental genotoxic potential of emissions from a complex of ceramic industries in Monte Carmelo, Minas Gerais, Brazil, using Tradescantia pallida. AB - The micronucleus (MN) test and analysis of heavy metal biological accumulation in Tradescantia pallida (T. pallida) were bioassays used to assess the genotoxic potential of emissions from a complex of ceramic industries into the atmosphere in a city in Brazil that is considered a national reference source for roof tile production. The ceramic industry emission-exposed T. pallida plants were biomonitored during the dry season, in June, July, and August 2013. In addition to the contaminated monitoring site, a reference site in a peri-urban area was utilized, for comparative purposes. Genotoxicity assessments were determined monthly, while heavy metal bioaccumulation was measured at the end of the total exposure period. The MN frequency was significantly greater in T. pallida plants exposed in the ceramic industry emission monitored area compared to the reference site, and highest MN rates were observed in July and August. With respect to heavy metal bioaccumulation in T. pallida leaves, cadmium (Cd) and chromium (Cr) concentrations were significantly higher in plants at the ceramic industry emission monitoring site. Thus, in relation to the parameters assessed, T. pallida was found to be sensitive to atmospheric contamination by heavy metals attributed to ceramic products emissions generated by the ceramic industry, confirming that this plant species may be employed as a reference organism in biomonitoring studies. PMID- 26818188 TI - CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients. AB - Strategies that enhance the function of T cells are critical for immunotherapy. One negative regulator of T-cell activity is ligand PD-L1, which is expressed on dentritic cells (DCs) or some tumor cells, and functions through binding of programmed death-1 (PD-1) receptor on activated T cells. Here we described for the first time a non-viral mediated approach to reprogram primary human T cells by disruption of PD-1. We showed that the gene knockout of PD-1 by electroporation of plasmids encoding sgRNA and Cas9 was technically feasible. The disruption of inhibitory checkpoint gene PD-1 resulted in significant reduction of PD-1 expression but didn't affect the viability of primary human T cells during the prolonged in vitro culture. Cellular immune response of the gene modified T cells was characterized by up-regulated IFN-gamma production and enhanced cytotoxicity. These results suggest that we have demonstrated an approach for efficient checkpoint inhibitor disruption in T cells, providing a new strategy for targeting checkpoint inhibitors, which could potentialy be useful to improve the efficacy of T-cell based adoptive therapies. PMID- 26818190 TI - Relationships between social factors and physical activity among elderly survivors of the Great East Japan earthquake: a cross-sectional study. AB - BACKGROUND: Physical inactivity is a health issue that often occurs after serious disaster. Social factors, which can be disrupted by disaster, are important determinants of physical activity levels in everyday living. This study was designed to confirm the association between social factors and physical activity among elderly survivors of the Great East Japan Earthquake. METHODS: From September 2011 to February 2012, 4316 males and females aged 65 or older participated in a health survey of Great East Japan Earthquake survivors. Multiple logistic regression analyses were performed with the dichotomous dependent variable of physical activity (high versus low) and working status, social network, and place of residence (one's own home versus elsewhere) as independent variables. RESULTS: Participants who had been displaced from their homes were more likely to have low physical activity (odds ratio [OR], 95% confidence interval [CI] for men: 1.37, 1.12 to 1.68; for women: 1.30, 1.09 to 1.55). Non-working status was significantly associated with low physical activity (men: 2.03, 1.65 to 2.49; women: 1.94, 1.60 to 2.34). Detriments to the social network were significantly associated with low physical activity (men: 1.71, 1.41 to 2.08; women: 1.79, 1.51 to 2.13). CONCLUSION: Place of residence and social factors were associated with physical activity levels in elderly survivors of the Great East Japan Earthquake. The findings suggest a need for improvement of social factors to encourage increases in physical activity for elderly persons after disaster. PMID- 26818191 TI - Wnt11 plays an important role in the osteogenesis of human mesenchymal stem cells in a PHA/FN/ALG composite scaffold: possible treatment for infected bone defect. AB - BACKGROUND: Infected bone defect poses a great challenge for orthopedists because it is difficult to cure. Tissue-engineered bone based on the human mesenchymal stem cells (hMSCs), has currently taken a promising treatment protocol in clinical practice. In a previous study, a porous hydroxyapatite/fibronectin/alginate (PHA/FN/ALG) composite scaffold displayed favorable biological properties as a novel scaffold, which was considered better than single-material scaffolds. In addition, Wnt11 has been demonstrated to play an important role in the development of osteoblasts, but until recently, its role in the osteogenic differentiation of hMSCs in infectious environment remained unclear. METHODS: In this study, we constructed a PHA/FN/ALG composite scaffold with layer-by-layer technology. Furthermore, we also constructed Wnt11-silenced (RNAi) and -overexpressing hMSCs by lentiviral transduction. The gene transduction efficacy was confirmed by quantitative PCR assay and Western blot analysis. Tissue-engineered bone was constructed with hMSCs and PHA/FN/ALG composite scaffolds, and then was implanted into an infected bone defect model for evaluating the osteogenic capacity by quantitative PCR, gross observation, micro-CT and histology analysis. RESULTS: All those cells showed similar adhesion abilities and proliferation capacities in scaffolds. After tissue-engineered bone implantation, there were high levels of systemic inflammatory factors in vivo, which significantly declined three days after antibiotic therapy. One or two months after implantation, the results of osteogenic-related gene analyses, gross observation, micro-CT and histology consistently showed that the Wnt11 over expression hMSC group displayed the strongest osteogenesis capacity, whereas the Wnt11-RNAi hMSC group displayed inferior osteogenesis capacity, when compared with the other cell-containing groups. However, the blank control group and the only composite scaffold without cell implantation group both showed extremely weak osteogenesis capacity. CONCLUSION: Our results revealed that the Wnt11 gene plays an important role in hMSCs for enhancing the osteogenesis in an infectious environment. PMID- 26818192 TI - Clinical significance of postoperative recovery of serum albumin levels in patients with esophageal cancer who underwent transthoracic esophagectomy. AB - PURPOSE: We evaluated postoperative recovery after transthoracic esophagectomy using postoperative serum albumin (Alb) levels and investigated the correlation between postoperative Alb recovery and the survival of patients with esophageal cancer. METHODS: Esophageal cancer patients who underwent transthoracic esophagectomy were retrospectively reviewed. To evaluate postoperative Alb recovery, the recovery rate of Alb was used. We investigated the correlation between Alb recovery, clinicopathological factors, and the survival. Furthermore, the postoperative systemic inflammatory response was evaluated using serum C reactive levels, and its impact on the Alb recovery was examined. RESULTS: Ninety seven (51 %) of 191 patients were classified as having insufficient Alb recovery. In the multivariate survival analysis, pStage and insufficient Alb recovery (hazard ratio 1.863; P = 0.021) were significantly independent predictive factors for the overall survival. Patients with pStage IB-IV with insufficient Alb recovery had a significantly shorter recurrence-free survival (5-year recurrence free survival rate, 59.5 vs. 41.5 %; P = 0.035) and significantly higher serum CRP levels at POM 3 compared with patients with sufficient Alb recovery. CONCLUSIONS: Insufficient Alb recovery correlates with the systemic postoperative inflammatory response and a poor prognosis. Further studies are warranted to investigate the survival benefit of intervention to enhance postoperative Alb recovery. PMID- 26818193 TI - A comprehensive mapping of the current capacity for human nutrition training in Cameroon. AB - BACKGROUND: There is consensus among stakeholders in Cameroon on the need to develop and strengthen human resource capacity for nutrition. This study was conducted to provide a comprehensive mapping of the current capacity for tertiary level human nutrition training in Cameroon. DESIGN: Participating institutions included university-level institutions offering dedicated nutrition degree programs or other programs in which nutrition courses were taught. A semi structured questionnaire administered during in-person interviews was used to collect data on existing programs and content of training curricula. Nutrition curricula were reviewed against the following criteria: intended objectives, coverage of nutrition topics, and teaching methods. RESULTS: In total, five nutrition degree programs (four undergraduate programs and one master's program) were identified. Three additional programs were about to be launched at the time of data collection. We did not find any doctorate degree programs in nutrition. All the undergraduate programs only had little focus on public health nutrition whereas the master's program in our sample offered a good coverage of all dimensions of human nutrition including basic and applied nutrition. The predominant teaching method was didactic lecture in all the programs. We did not find any formal documentation outlining the competencies that students were expected to gain upon completion of these programs. Nutrition courses in agricultural and health schools were limited in terms of contact hours and scope. Public health nutrition was not covered in any of the health professional schools surveyed. We found no institution offering in-service nutrition training at the time of the study. CONCLUSIONS: Based on our findings, we recommend that nutrition training programs in Cameroon be redesigned to make them more responsive to the public health needs of the country. PMID- 26818194 TI - Adolescent depression, adult mental health and psychosocial outcomes at 30 and 35 years. AB - BACKGROUND: There is limited information on long-term outcomes of adolescent depression. This study examines the associations between severity of depression in adolescence and a broad array of adult functional outcomes. METHOD: Data were gathered as part of the Christchurch Health and Development Study, a 35-year longitudinal study of a birth cohort of 1265 children born in Christchurch, New Zealand in 1977. Severity of depression at age 14-16 years was classified into three levels according to DSM symptom criteria for major depression (no depression/sub-threshold symptoms/major depression). This classification was related to adult functional outcomes assessed at ages 30 and 35 years using a generalized estimating equation modeling approach. Outcome measures spanned domains of mental disorder, education/economic circumstances, family circumstances and partner relationships. RESULTS: There were modest but statistically significant bivariate associations between adolescent depression severity and most outcomes. After covariate adjustment there remained weak but significant (p < 0.05) associations with rates of major depression, anxiety disorder, illicit substance abuse/dependence, any mental health problem and intimate partner violence (IPV) victimization. Estimates of attributable risk for these outcomes ranged from 3.8% to 7.8%. For two outcomes there were significant (p < 0.006) gender interactions such that depression severity was significantly related to increased rates of unplanned pregnancy and IPV victimization for females but not for males. CONCLUSIONS: The findings reinforce the importance of the individual/family context in which adolescent depression occurs. When contextual factors and probable maturational effects are taken into account the direct effects of adolescent depression on functioning in mature adulthood appear to be very modest. PMID- 26818196 TI - Governments Need Better Guidance to Maximise Value for Money: The Case of Australia's Pharmaceutical Benefits Advisory Committee. AB - In Australia, the Pharmaceutical Benefits Advisory Committee (PBAC) makes recommendations to the Minister for Health on which pharmaceuticals should be subsidised. Given the implications of PBAC recommendations for government finances and population health, PBAC is required to provide advice primarily on the basis of value for money. The aim of this article is twofold: to describe some major limitations of the current PBAC decision-making process in relation to its implicit aim of maximising value for money; and to suggest what might be done toward overcoming these limitations. This should also offer lessons for the many decision-making bodies around the world that are similar to PBAC. The current PBAC decision-making process is limited in two important respects. First, it features the use of an implicit incremental cost-effectiveness ratio (ICER) threshold that may not reflect the opportunity cost of funding a new technology, with unknown and possibly negative consequences for population health. Second, the process does not feature a means of systematically assessing how a technology may be of greater or lesser value in light of factors that are not captured by standard measures of cost effectiveness, but which are nonetheless important, particularly to the Australian community. Overcoming these limitations would mean that PBAC could be more confident of maximising value for money when making funding decisions. PMID- 26818195 TI - Prevalence, Clinical Characteristics, and Risk Factors for Non-recording of Alcohol Use in Hospitals across Europe: The ALCHIMIE Study. AB - AIM: To determine the detection rates, clinical features, and risk factors for lack of registration of alcohol use in medical patients admitted in European hospitals. METHODS: A point-prevalence, cross-sectional, multicenter survey involving 2100 medical inpatients from 43 hospitals from 8 European countries. Patients were screened for current alcohol use, using standardized questionnaires. Alcohol use recording in medical records was assessed. RESULTS: Of the 2100, more than a half reported alcohol use. Significant differences were shown in the prevalence of drinking and the recording rates of alcohol use among the hospitals and countries involved. Overall, 346 patients (16%) fulfilled criteria for alcohol use disorder. Alcohol use was registered in 909 (43%) of medical records, with quantification in 143 (7%). Multivariate analysis showed that women (OR 1.49), older age patients (OR 1.23), patients from the Northern European countries (OR 4.79) and from hospitals with high local alcohol prevalence (OR 1.59) were more likely to have lack of alcohol use registration in their medical files. CONCLUSIONS: A considerable proportion of medical patients admitted in European hospitals fulfill criteria for alcohol use disorders. These patients are frequently overlooked during hospitalization and not appropriately registered in medical records. Women, older patients, and inpatients from European areas with high local alcohol use prevalence are at higher risk associated with a non-recording of alcohol use. PMID- 26818197 TI - The TURis System for Transurethral Resection of the Prostate: A NICE Medical Technology Guidance. AB - The transurethral resection in saline (TURis) system was notified by the company Olympus Medical to the National Institute of Health and Care Excellence's (NICE's) Medical Technologies Evaluation Programme. Following selection for medical technologies guidance, the company developed a submission of clinical and economic evidence for evaluation. TURis is a bipolar surgical system for treating men with lower urinary tract symptoms due to benign prostatic enlargement. The comparator is any monopolar transurethral resection of the prostate (mTURP) system. Cedar, a collaboration between Cardiff and Vale University Health Board, Cardiff University and Swansea University in the UK, acted as an External Assessment Centre (EAC) for NICE to independently critique the company's submission of evidence. Eight randomised trials provided evidence for TURis, demonstrating efficacy equivalent to that of mTURP for improvement of symptoms. The company presented meta-analyses of key outcome measures, and the EAC made methodological modifications in response to the heterogeneity of the trial data. The EAC analysis found that TURis substantially reduced the relative risks of transurethral resection syndrome (relative risk 0.18 [95 % confidence interval 0.05-0.62]) and blood transfusion (relative risk 0.35 [95 % confidence interval 0.19-0.65]). The company provided a de novo economic model comparing TURis with mTURP. The EAC critiqued the model methodology and made modifications. This found TURis to be cost saving at L70.55 per case for existing Olympus customers and cost incurring at L19.80 per case for non-Olympus customers. When an additional scenario based on the only available data on readmission (due to any cause) from a single trial was modelled, the estimated cost saving per case was L375.02 for existing users of Olympus electrosurgery equipment and L284.66 per case when new Olympus equipment would need to be purchased. Meta-analysis of eight randomised trials showed that TURis is associated with a statistically significantly reduced risk of transurethral resection syndrome and a reduced need for blood transfusion two factors that may drive cost saving for the National Health Service. The clinical data are equivocal as to whether TURis shortens the hospital stay. Limited data from a single study suggest that TURis may reduce the rate of readmission after surgery. The NICE guidance supports adoption of the TURis technology for performing transurethral resection of the prostate in men with lower urinary tract symptoms due to benign prostatic enlargement. PMID- 26818198 TI - A Systematic Review of the Literature on the Development of Condition-Specific Preference-Based Measures of Health. AB - BACKGROUND: Health state utility values (HSUVs) are required to calculate quality adjusted life-years (QALYs). They are frequently derived from generic preference based measures of health. However, such generic measures may not capture health attributes of relevance to specific conditions. In such cases, a condition specific preference-based measure (CSPBM) may be more appropriate. OBJECTIVE: This systematic review aimed to identify all published accounts of developing CSPBMs to describe and appraise the methods used. METHOD: We undertook a systematic search (of Embase, MEDLINE, PsycINFO, Web of Science, the Cochrane Library, CINAHL, EconLit, ASSIA and the Health Management Information Consortium database) to identify published accounts of CSPBM development up to July 2015. Studies were reviewed to investigate the methods used to design classification systems, estimate HSUVs, and validate the measures. RESULTS: A total of 86 publications were identified, describing 51 CSPBMs. Around two-thirds of these were QALY measures; the remainder were designed for clinical decision making only. Classification systems for 33 CSPBMs were derived from existing instruments; 18 were developed de novo. HSUVs for 34 instruments were estimated using a 'composite' approach, involving statistical modelling; the remainder used a 'decomposed' approach based on multi-attribute utility theory. Half of the papers that described the estimation of HSUVs did not report validating their measures. CONCLUSION: Various methods have been used at all stages of CSPBM development. The choice between developing a classification system de novo or from an existing instrument may depend on the availability of a suitable existing measure, while the choice between a decomposed or composite approach appears to be determined primarily by the purpose for which the instrument is designed. The validation of CSPBMs remains an area for further development. PMID- 26818200 TI - Patients' perspectives on the impact of fasting while in hospital. PMID- 26818201 TI - Similar quit rates are found with three smoking cessation options. PMID- 26818199 TI - p53 deficiency linked to B cell translocation gene 2 (BTG2) loss enhances metastatic potential by promoting tumor growth in primary and metastatic sites in patient-derived xenograft (PDX) models of triple-negative breast cancer. AB - BACKGROUND: Despite advances in early diagnosis and treatment of cancer patients, metastasis remains the major cause of mortality. TP53 is one of the most frequently mutated genes in human cancer, and these alterations can occur during the early stages of oncogenesis or as later events as tumors progress to more aggressive forms. Previous studies have suggested that p53 plays a role in cellular pathways that govern metastasis. To investigate how p53 deficiency contributes to late-stage tumor growth and metastasis, we developed paired isogenic patient-derived xenograft (PDX) models of triple-negative breast cancer (TNBC) differing only in p53 status for longitudinal analysis. METHODS: Patient derived isogenic human tumor lines differing only in p53 status were implanted into mouse mammary glands. Tumor growth and metastasis were monitored with bioluminescence imaging, and circulating tumor cells (CTCs) were quantified by flow cytometry. RNA-Seq was performed on p53-deficient and p53 wild-type tumors, and functional validation of a lead candidate gene was performed in vivo. RESULTS: Isogenic p53 wild-type and p53-deficient tumors metastasized out of mammary glands and colonized distant sites with similar frequency. However, p53 deficient tumors metastasized earlier than p53 wild-type tumors and grew faster in both primary and metastatic sites as a result of increased proliferation and decreased apoptosis. In addition, greater numbers of CTCs were detected in the blood of mice engrafted with p53-deficient tumors. However, when normalized to tumor mass, the number of CTCs isolated from mice bearing parental and p53 deficient tumors was not significantly different. Gene expression profiling followed by functional validation identified B cell translocation gene 2 (BTG2), a downstream effector of p53, as a negative regulator of tumor growth both at primary and metastatic sites. BTG2 expression status correlated with survival of TNBC patients. CONCLUSIONS: Using paired isogenic PDX-derived metastatic TNBC cells, loss of p53 promoted tumor growth and consequently increased tumor cell shedding into the blood, thus enhancing metastasis. Loss of BTG2 expression in p53-deficient tumors contributed to this metastatic potential by enhancing tumor growth in primary and metastatic sites. Furthermore, clinical data support conclusions generated from PDX models and indicate that BTG2 expression is a candidate prognostic biomarker for TNBC. PMID- 26818202 TI - Cutaneous Presentation of Methicillin-Resistant Staphylococcus aureus Sepsis in a Healthy Child. PMID- 26818204 TI - Response to parenteral iron therapy distinguish unexplained refractory iron deficiency anemia from iron-refractory iron deficiency anemia. AB - INTRODUCTION: We evaluated that response to parenteral iron therapy could be helpful in distinguishing the types of iron deficiency anemia. PATIENTS AND METHODS: This study analyzed responses to IV iron sucrose therapy of 15 children with unexplained refractory iron deficiency anemia (URIDA). We compared the results at diagnosis, 6 weeks and 6 months after the therapy. Results were compared with responses of 11 patients' results with iron-refractory iron deficiency anemia (IRIDA) from our previous study. RESULT: Six weeks after the start of treatment, ferritin, MCV, MCH and Hb values were in normal range in 10 patients. The increase in Hb, MCH, MCV, and ferritin values ranged 2.6-3.5 g/dL, 1.7-4.2 pg, 2-9 fL, and 13-25 ng/mL, respectively. In five patients, Hb, MCH, and MCV mean (range) values [11.2 g/dL (11-12.2), 24.5 pg (24-25.6), and 67 fL (65 70)] were nearly normal but ferritin mean (range) values [9.8 ng/mL (8-11)] were below normal. Six weeks after the start of treatment, Hb, MCH, MCV and ferritin values of patients with IRIDA were increased. The increase in Hb, MCH, MCV, and ferritin values ranged 0.8-2.7 g/dL, 1.7-4.2 pg, 2-9 fL, and 13-25 ng/mL, respectively. IRIDA is only partially responsive to parenteral iron supplementation. In conclusion, this study demonstrated that the response to intravenous iron therapy for the URIDA cases improved blood parameters more effectively than hereditary IRIDA. Response to parenteral iron therapy would be helpful to distinguish unexplained refractory IDA from hereditary IRIDA for clinicians who do not have access to hepcidin or TMPRS6 mutation analysis. PMID- 26818203 TI - Handgrip strength is associated with metabolic syndrome among middle-aged and elderly community-dwelling persons. AB - The association of low muscle strength with cardio-metabolic risks remains controversial. The present study included 742 men aged 70 +/- 9 years and 937 women aged 70 +/- 8 years from a rural village. We examined the cross-sectional relationship between relative muscle strength defined by handgrip strength (HGS)/body weight (BW) ratio, and metabolic syndrome (MetS) based on the modified criteria of the National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP) III report and its components. Of these, 203 men (27.4%) and 448 women (47.8%) had MetS. In men, increasing quartile of HGS/BW ratio was significantly and independently associated with high waist circumference {odds ratio, 0.31; 95% confidence interval (CI), 0.24-0.41} and elevated triglyceridemia (0.71, 0.59 0.86). In women, it was also significantly and independently associated with high waist circumference (0.41; 0.36-0.48), high blood pressure (0.78; 0.66-0.92), Low HDL-cholesterolemia (0.84; 0.73-0.98) and elevated triglyceridemia (0.65; 0.53 0.79). In both genders, the prevalence of MetS significantly decreased in relation to increasing HGS/BW ratio. After adjustment for age, smoking status, drinking status, LDL-C, estimated glomerular filtration ratio (eGFR), and medication, the respective odds ratio (95% CI) for the quartile of HGS/BW ratio for MetS was 1.00, 0.54 (0.34-0.85), 0.32 (0.19-0.53), and 0.16 (0.09-0.29) in men, and 1.00, 0.76 (0.50-1.16), 0.33 (0.22-0.51), and 0.16 (0.10-0.25) in women. These results suggest that HGS/BW ratio was significantly and negatively associated with an increased risk of cardio-metabolic disorders in Japanese community dwelling persons. PMID- 26818205 TI - Quantitative assessment of developmental levels in overarm throwing using wearable inertial sensing technology. AB - Motor proficiency in childhood has been recently recognised as a public health determinant, having a potential impact on the physical activity level and possible sedentary behaviour of the child later in life. Among fundamental motor skills, ballistic skills assessment based on in-field quantitative observations is progressively needed in the motor development community. The aim of this study was to propose an in-field quantitative approach to identify different developmental levels in overarm throwing. Fifty-eight children aged 5-10 years performed an overarm throwing task while wearing three inertial sensors located at the wrist, trunk and pelvis level and were then categorised using a developmental sequence of overarm throwing. A set of biomechanical parameters were defined and analysed using multivariate statistics to evaluate whether they can be used as developmental indicators. Trunk and pelvis angular velocities and time durations before the ball release showed increasing/decreasing trends with increasing developmental level. Significant differences between developmental level pairs were observed for selected biomechanical parameters. The results support the suitability and feasibility of objective developmental measures in ecological learning contexts, suggesting their potential supportiveness to motor learning experiences in educational and youth sports training settings. PMID- 26818206 TI - Effectiveness of low-dose pregabalin in three patients with Lewy body disease and central neuropathic pain. AB - Many patients with Lewy body disease complain of pain, and their pain may be associated with this disease. Recently, pain has become a focus of attention in Parkinson's disease, but there is little information regarding pain in patients who have dementia with Lewy bodies. We used pregabalin to treat three Lewy body disease patients with chronic pain that may have been related to degeneration of central neurons. All three patients responded well to pregabalin at 25-50 mg/day. To our knowledge, there have been no previous reports of pregabalin showing efficacy for central neuropathic pain in Parkinson's disease or Lewy body disease. PMID- 26818207 TI - Data processing can mask biology: towards better reporting of fungal barcoding data? PMID- 26818208 TI - The Facial Artery-The Main Blood Vessel for the Anterior Face? AB - BACKGROUND: The facial artery is said to be the main vessel for the blood supply of the anterior face. However, its course is quite often not as described in the textbooks. OBJECTIVE: The purpose of this study was to find out the different courses of the facial artery, its anastomoses, and its position in relation to the fat compartments of the face. MATERIALS AND METHODS: With 60 hemifaces three dimensional reconstructions with computed tomography, cross dissections and horizontal sections were performed. RESULTS: Of note, 4 types of facial arteries were identified. Not even half of the specimens showed a textbook course of the facial artery and only a quarter of the specimens had a textbook course of the artery on both sides. CONCLUSION: To know the different appearances of the facial artery can be helpful for filler injection in aesthetic medicine but also for planning flaps in reconstructive surgery. PMID- 26818209 TI - Melanoma Outcomes in Transplant Recipients With Pretransplant Melanoma. AB - BACKGROUND: There are limited data on outcomes in transplant recipients with a history of pretransplant melanoma. OBJECTIVE: To determine whether pretransplant melanoma is associated with differences in survival or posttransplant melanoma risk. MATERIALS AND METHODS: We evaluated the outcomes of 185,039 US transplant recipients from the Transplant Cancer Match Study. We also evaluated the impact of transplantation on 141,441 patients with melanoma identified in cancer registries. RESULTS: There were 336 transplant recipients (0.18%) with pretransplant melanoma; they had increased risk of melanoma-specific mortality (hazard ratio [HR], 27; 95% confidence interval [CI], 11-64, p < .0001), overall mortality (HR, 1.3; 95% CI, 1.0-1.5, p = .02), and incident melanoma (HR, 5.4; 95% CI, 2.9-9.8, p < .0001) after transplant, compared with recipients without pretransplant melanoma. The 10-year absolute risk difference was 2.97% for melanoma-specific mortality, 3.68% for incident melanoma, and 14.32% for overall mortality. Among the 141,441 patients with melanoma in the general population, 68 (0.05%) subsequently received a transplant. Transplantation increased melanoma specific mortality, but not significantly (HR, 1.7; 95% CI, 0.61-4.5, p = .32). CONCLUSION: Pretransplant melanoma is associated with increased melanoma-specific mortality, overall mortality, and incident melanoma after transplant. Nonetheless, the rarity of melanoma-related events supports the current practice for listing transplant candidates with a history of melanoma. PMID- 26818211 TI - The first case of acute unilateral pan-ureteritis caused by BK polyomavirus in an allogeneic stem cell transplant patient. AB - Several cases of ureteral obstruction have been reported in stem cell transplant (SCT) patients; however, they were bilateral and concomitant with or preceded by hemorrhagic cystitis. We describe, to our knowledge, a first case of acute unilateral pan-ureteritis caused by BK polyomavirus (BKPyV) in an SCT patient. This case may represent an early phase of BKPyV reactivation. BKPyV infection should be considered as a potential cause of acute unilateral ureteritis even among SCT recipients. PMID- 26818210 TI - Recombinant pre-miR-29b for Alzheimer's disease therapeutics. AB - MicroRNAs are arising as the next generation of diagnostic and therapeutic tools for gene silencing. Studies demonstrated that the miR-29 expression is decreased in Alzheimer's disease (AD) patients displaying high levels of human beta secretase (hBACE1). Recent advances toward an effective therapy for AD intend to employ miR-29 to suppress hBACE1 expression and subsequent Amyloid-beta (Abeta) peptide. However, delivery of mature miRNA has demonstrated modest efficacy in vitro; therefore, the preparation of highly pure and biologically active pre miRNA arises as one of the most important challenges in the development of these therapeutic strategies. Recently, we described a new strategy based arginine affinity chromatography to specifically purify the recombinant pre-miR-29b. Following this strategy, the purified pre-miR-29b was successfully encapsulated into polyplexes that were further delivered in cytoplasm. It was verified that Chitosan/pre-miR-29b and Polyethylenimine/pre-miR-29b systems efficiently delivered pre-miR-29b to N2a695 cells, thus reducing the hBACE1 protein expression (around 78% and 86%, respectively) and Abeta42 levels (approximately 44% and 47%, respectively). Furthermore, pre-miR-29b downregulates the hBACE1 mRNA expression in 80%. Overall, it was demonstrated that the recombinant pre-miR 29b using polyplexes allowed to decrease the hBACE1 and Abeta42 expression levels, improving the currently available methodologies of miRNA-based therapeutics. PMID- 26818213 TI - A MEMS-based heating holder for the direct imaging of simultaneous in-situ heating and biasing experiments in scanning/transmission electron microscopes. AB - The introduction of scanning/transmission electron microscopes (S/TEM) with sub Angstrom resolution as well as fast and sensitive detection solutions support direct observation of dynamic phenomena in-situ at the atomic scale. Thereby, in situ specimen holders play a crucial role: accurate control of the applied in situ stimulus on the nanostructure combined with the overall system stability to assure atomic resolution are paramount for a successful in-situ S/TEM experiment. For those reasons, MEMS-based TEM sample holders are becoming one of the preferred choices, also enabling a high precision in measurements of the in-situ parameter for more reproducible data. A newly developed MEMS-based microheater is presented in combination with the new NanoExTM-i/v TEM sample holder. The concept is built on a four-point probe temperature measurement approach allowing active, accurate local temperature control as well as calorimetry. In this paper, it is shown that it provides high temperature stability up to 1,300 degrees C with a peak temperature of 1,500 degrees C (also working accurately in gaseous environments), high temperature measurement accuracy (<4%) and uniform temperature distribution over the heated specimen area (<1%), enabling not only in-situ S/TEM imaging experiments, but also elemental mapping at elevated temperatures using energy-dispersive X-ray spectroscopy (EDS). Moreover, it has the unique capability to enable simultaneous heating and biasing experiments. PMID- 26818212 TI - Enhanced performance of macrophage-encapsulated nanoparticle albumin-bound paclitaxel in hypo-perfused cancer lesions. AB - Hypovascularization in tumors such as liver metastases originating from breast and other organs correlates with poor chemotherapeutic response and higher mortality. Poor prognosis is linked to impaired transport of both low- and high molecular weight drugs into the lesions and to high washout rate. Nanoparticle albumin-bound-paclitaxel (nAb-PTX) has demonstrated benefits in clinical trials when compared to paclitaxel and docetaxel. However, its therapeutic efficacy for breast cancer liver metastasis is disappointing. As macrophages are the most abundant cells in the liver tumor microenvironment, we design a multistage system employing macrophages to deliver drugs into hypovascularized metastatic lesions, and perform in vitro, in vivo, and in silico evaluation. The system encapsulates nAb-PTX into nanoporous biocompatible and biodegradable multistage vectors (MSV), thus promoting nAb-PTX retention in macrophages. We develop a 3D in vitro model to simulate clinically observed hypo-perfused tumor lesions surrounded by macrophages. This model enables evaluation of nAb-PTX and MSV-nab PTX efficacy as a function of transport barriers. Addition of macrophages to this system significantly increases MSV-nAb-PTX efficacy, revealing the role of macrophages in drug transport. In the in vivo model, a significant increase in macrophage number, as compared to unaffected liver, is observed in mice, confirming the in vitro findings. Further, a mathematical model linking drug release and retention from macrophages is implemented to project MSV-nAb-PTX efficacy in a clinical setting. Based on macrophage presence detected via liver tumor imaging and biopsy, the proposed experimental/computational approach could enable prediction of MSV-nab PTX performance to treat metastatic cancer in the liver. PMID- 26818214 TI - Arbuscular mycorrhizal fungi regulate soil respiration and its response to precipitation change in a semiarid steppe. AB - Arbuscular mycorrhizal fungi (AMF) are critical links in plant-soil continuum and play a critical role in soil carbon cycles. Soil respiration, one of the largest carbon fluxes in global carbon cycle, is sensitive to precipitation change in semiarid ecosystems. In this study, a field experiment with fungicide application and water addition was conducted during 2010-2013 in a semiarid steppe in Inner Mongolia, China, and soil respiration was continuously measured to investigate the influences of AMF on soil respiration under different precipitation regimes. Results showed that soil respiration was promoted by water addition treatment especially during drought seasons, which induced a nonlinear response of soil respiration to precipitation change. Fungicide application suppressed AMF root colonization without impacts on soil microbes. AMF suppression treatment accelerated soil respiration with 2.7, 28.5 and 37.6 g C m(-2) across three seasons, which were mainly caused by the enhanced heterotrophic component. A steeper response of soil respiration rate to precipitation was found under fungicide application treatments, suggesting a greater dampening effect of AMF on soil carbon release as water availability increased. Our study highlighted the importance of AMF on soil carbon stabilization and sequestration in semiarid steppe ecosystems especially during wet seasons. PMID- 26818215 TI - Comparison of hypoxia-activated prodrug evofosfamide (TH-302) and ifosfamide in preclinical non-small cell lung cancer models. AB - Evofosfamide (TH-302) is a hypoxia-activated prodrug of the cytotoxin bromo isophosphoramide. In hypoxic conditions Br-IPM is released and alkylates DNA. Ifosfamide is a chloro-isophosphoramide prodrug activated by hepatic Cytochrome P450 enzymes. Both compounds are used for the treatment of cancer. Ifosfamide has been approved by the FDA while evofosfamide is currently in the late stage of clinical development. The purpose of this study is to compare efficacy and safety profile of evofosfamide and ifosfamide in preclinical non-small cell lung cancer H460 xenograft models. Immunocompetent CD-1 mice and H460 tumor-bearing immunocompromised nude mice were used to investigate the safety profile. The efficacy of evofosfamide or ifosfamide, alone, and in combination with docetaxel or sunitinib was compared in ectopic and intrapleural othortopic H460 xenograft models in animals exposed to ambient air or different oxygen concentration breathing conditions. At an equal body weight loss level, evofosfamide showed greater or comparable efficacy in both ectopic and orthotopic H460 xenograft models. Evofosfamide, but not ifosfamide, exhibited controlled oxygen concentration breathing condition-dependent antitumor activity. However, at an equal body weight loss level, ifosfamide yielded severe hematologic toxicity when compared to evofosfamide, both in monotherapy and in combination with docetaxel. At an equal hematoxicity level, evofosfamide showed superior antitumor activity. These results indicate that evofosfamide shows superior or comparable efficacy and a favorable safety profile when compared to ifosfamide in preclinical human lung carcinoma models. This finding is consistent with multiple clinical trials of evofosfamide as a single agent, or in combination therapy, which demonstrated both anti-tumor activity and safety profile without severe myelosuppression. PMID- 26818217 TI - Automated Agitation-Assisted Demulsification Dispersive Liquid-Liquid Microextraction. AB - Dispersive liquid-liquid microextraction (DLLME) is an extremely fast and efficient sample preparation procedure. For its capability and applicability to be fully exploited, full automation of its operations seamlessly integrated with analysis is necessary. In this work, for the first time, fully automated agitation-assisted demulsification (AAD)-DLLME integrated with gas chromatography/mass spectrometry was developed for the convenient and efficient determination of polycyclic aromatic hydrocarbons in environmental water samples. The use of a commercially available multipurpose autosampler equipped with two microsyringes of different capacities allowed elimination or significant reduction of manpower, labor, and time with the large-volume microsyringe used for liquid transfers and the small-volume microsyringe for extract collection and injection for analysis. Apart from enhancing accessibility of DLLME, the procedure was characterized by the application of agitation after extraction to break up the emulsion (that otherwise would need centrifugation or a demulsification solvent), further improving overall operational efficiency and flexibility. Additionally, the application of low-density solvent as extractant facilitated the easy collection of extract as the upper layer over water. Some parameters affecting the automated AAD-DDLME procedure were investigated. Under the optimized conditions, the procedure provided good linearity (ranging from a minimum of 0.1-0.5 MUg/L to a maximum of 50 MUg/L), low limits of detection (0.010-0.058 MUg/L), and good repeatability of the extractions (relative standard deviations, below 5.3%, n = 6). The proposed method was applied to analyze PAHs in real river water samples. PMID- 26818218 TI - Combining random forest and 2D correlation analysis to identify serum spectral signatures for neuro-oncology. AB - Fourier transform infrared (FTIR) spectroscopy has long been established as an analytical technique for the measurement of vibrational modes of molecular systems. More recently, FTIR has been used for the analysis of biofluids with the aim of becoming a tool to aid diagnosis. For the clinician, this represents a convenient, fast, non-subjective option for the study of biofluids and the diagnosis of disease states. The patient also benefits from this method, as the procedure for the collection of serum is much less invasive and stressful than traditional biopsy. This is especially true of patients in whom brain cancer is suspected. A brain biopsy is very unpleasant for the patient, potentially dangerous and can occasionally be inconclusive. We therefore present a method for the diagnosis of brain cancer from serum samples using FTIR and machine learning techniques. The scope of the study involved 433 patients from whom were collected 9 spectra each in the range 600-4000 cm(-1). To begin the development of the novel method, various pre-processing steps were investigated and ranked in terms of final accuracy of the diagnosis. Random forest machine learning was utilised as a classifier to separate patients into cancer or non-cancer categories based upon the intensities of wavenumbers present in their spectra. Generalised 2D correlational analysis was then employed to further augment the machine learning, and also to establish spectral features important for the distinction between cancer and non-cancer serum samples. Using these methods, sensitivities of up to 92.8% and specificities of up to 91.5% were possible. Furthermore, ratiometrics were also investigated in order to establish any correlations present in the dataset. We show a rapid, computationally light, accurate, statistically robust methodology for the identification of spectral features present in differing disease states. With current advances in IR technology, such as the development of rapid discrete frequency collection, this approach is of importance to enable future clinical translation and enables IR to achieve its potential. PMID- 26818216 TI - Mortality Among Persons With Obsessive-Compulsive Disorder in Denmark. AB - IMPORTANCE: Several mental disorders have consistently been found to be associated with decreased life expectancy, but little is known about whether this is also the case for obsessive-compulsive disorder (OCD). OBJECTIVE: To determine whether persons who receive a diagnosis of OCD are at increased risk of death. DESIGN, SETTING, AND PARTICIPANTS: Using data from Danish registers, we conducted a nationwide prospective cohort study with 30 million person-years of follow-up. The data were collected from Danish longitudinal registers. A total of 3 million people born between 1955 and 2006 were followed up from January 1, 2002, through December 31, 2011. During this period, 27,236 people died. The data were analyzed primarily in June 2015. MAIN OUTCOMES AND MEASURES: We estimated mortality rate ratios (MRRs), adjusted for calendar year, age, sex, maternal and paternal age, place of residence at birth, and somatic comorbidities, to compare persons with OCT with persons without OCD. RESULTS: Of 10,155 persons with OCD (5935 women and 4220 men with a mean [SD] age of 29.1 [11.3] years who contributed a total of 54,937 person-years of observation), 110 (1.1%) died during the average follow-up of 9.7 years. The risk of death by natural or unnatural causes was significantly higher among persons with OCD (MRR, 1.68 [95% CI, 1.31-2.12] for natural causes; MRR, 2.61 [95% CI, 1.91-3.47] for unnatural causes) than among the general population. After the exclusion of persons with comorbid anxiety disorders, depression, or substance use disorders, OCD was still associated with increased mortality risk (MRR, 1.88 [95% CI, 1.27-2.67]). CONCLUSIONS AND RELEVANCE: The presence of OCD was associated with a significantly increased mortality risk. Comorbid anxiety disorders, depression, or substance use disorders further increased the risk. However, after adjusting for these and somatic comorbidities, we found that the mortality risk remained significantly increased among persons with OCD. PMID- 26818219 TI - Irreversible severe kidney injury and anuria in a 3-month-old girl with atypical haemolytic uraemic syndrome under administration of eculizumab. AB - Histopathological findings can play an important role in the management of atypical haemolytic uraemic syndrome (aHUS). We report a case of aHUS that did not recover from anuria, despite the administration of eculizumab, with impressive histopathological findings. A 3-month-old girl was admitted because of poor feeding, vomiting, and diarrhoea without haemorrhage. She had anuria and severe hypertension, and laboratory results showed haemolytic anaemia with schizocytes, thrombocytopenia, and renal impairment. Although no mutations in the complement system or diacylglycerol kinase epsilon were detected, she was diagnosed with aHUS owing to the clinical course and by the exclusion of Escherichia coli infection and thrombotic thrombocytopenic purpura. Plasma exchange was performed once at day 2 and eculizumab therapy was started from day 18, with a severe infusion reaction at the first administration. After the initiation of eculizumab, although the serum lactate dehydrogenase level improved gradually, she did not recover from anuria. Pathological findings of the kidney biopsy at day 37 included diffuse arteriolar and arterial luminal stenosis with remarkable thickness and sclerotic changes of the media and intima, which are suggestive of aHUS. In addition, most glomeruli had global sclerosis and were collapsed, and 80% of the tubulointerstitial compartment showed atrophic changes with infiltration of inflammatory cells. The present case is possibly a kidney specific fulminant type of aHUS. Although showing efficacy against thrombotic microangiopathy, eculizumab did not improve kidney function. The pathological findings reflected the severe and irreversible kidney injury. PMID- 26818220 TI - Kidney Allograft Abscess: An Unusual Cause of Peritonitis in a Patient on Peritoneal Dialysis. PMID- 26818221 TI - Tumoural calcinosis in a young woman. PMID- 26818222 TI - Comparison of the local and the average crystal structure of proton conducting lanthanum tungstate and the influence of molybdenum substitution. AB - We report on the comparison of the local and average structure reported recently for proton conducting lanthanum tungstate, of general formula La28 xW4+xO54+deltav2-delta, and the impact of molybdenum-substitution on the crystal structure of the material. Partial replacement of W with 10 and 30 mol% Mo is investigated here, i.e. La27(W1-xMox)5O55.5 for x = 0.1 and 0.3. This study addresses the interpretation and the description of a disordered cation and anion sublattice in this material, which enables the understanding of the fundamental properties related to hydration, transport properties and degradation in lanthanum tungstate. The report shows that Mo-substituted lanthanum tungstate is a promising material as a dense oxide membrane for hydrogen separation at intermediate temperatures. PMID- 26818223 TI - Parting Thoughts From the outgoing ISHD President, Dr. Madhukar Misra. PMID- 26818224 TI - Hemodialysis Abstracts from the 36th Annual Dialysis Conference February 27-March 1, 2016 Seattle, Washington. PMID- 26818226 TI - Pancreatitis: Fixing necrotizing pancreatitis. PMID- 26818227 TI - Markers of fibrinolysis may predict development of lower extremity arterial disease in patients with diabetes: A longitudinal prospective cohort study with 10 years of follow-up. AB - BACKGROUND: A previous cross-sectional study suggested that tissue plasminogen activator-activity might be an early marker of asymptomatic lower extremity arterial disease, but the long-term relationship is unknown. SUBJECTS AND METHODS: This study included 96 diabetic (48 type 1/48 type 2) and 62 non diabetic subjects aged 30-70 years without previously known lower extremity arterial disease (age: 50.3 +/- 9.3 years, gender: M/W 47.5/52.5% and body mass index: 26.6 +/- 4.5 kg/m(2)). The relationships between asymptomatic lower extremity arterial disease and fibrinolytic markers (tissue plasminogen activator activity, tissue plasminogen activator-mass, plasminogen activator inhibitor-1 activity) at baseline and after 10 years were assessed by logistic regression analysis adjusting for age, hypertension, statin treatment, HbA1c, triglycerides and low-density lipoprotein cholesterol as fixed covariates. RESULTS: The tissue plasminogen activator-activity at baseline and at the 10-year follow-up significantly predicted the presence of sign(s) of lower extremity arterial disease (odds ratio = 1.78, 95% confidence interval: 1.02-3.10, p = 0.043 and odds ratio = 1.78, 95% confidence interval: 1.12-2.23, p = 0.014, respectively). In addition, tissue plasminogen activator-mass at the 10-year follow-up was associated with signs of lower extremity arterial disease (odds ratio = 1.07, 95% confidence interval: 1.00-1.15, p = 0.046). Baseline age, hypertension and HbA1c were independently associated with sign(s) of lower extremity arterial disease at 10 years (odds ratio = 1.09, 95% confidence interval: 1.04-1.14, p = < 0.001; odds ratio = 3.68, 95% confidence interval: 1.67-8.12, p = 0.001 and odds ratio = 1.54, 95% confidence interval: 1.21-1.95, p = < 0.001, respectively). CONCLUSION: This long-term study supports previous findings of a significant association between asymptomatic lower extremity arterial disease and tissue plasminogen activator-activity. Thus, tissue plasminogen activator-activity may be an early marker of lower extremity arterial disease although the mechanism of this relationship remains unclear. PMID- 26818228 TI - A randomised controlled trial evaluating the impact of targeted vitamin D supplementation on endothelial function in type 2 diabetes mellitus: The DIMENSION trial. AB - We sought to determine if vitamin D supplementation, to target 25(OH)D concentrations of 30-40 ng/mL, improves endothelial function in Singapore's multi ethnic type 2 diabetes mellitus population. We randomised 64 type 2 diabetes mellitus patients with hypovitaminosis D to cholecalciferol 4000 International Unit/matching placebo [baseline 25(OH)D < 20 ng/mL] or cholecalciferol 2000 International Unit/matching placebo [baseline 25(OH)D: 20-30 ng/mL] daily for 16 weeks with a down titration at 8 weeks if 25(OH)D > 30 ng/mL. Endothelial function was assessed by peripheral tonometry (reactive hyperaemia index endothelial peripheral arterial tonometry) and vascular biomarkers: E-selectin, von-Willebrand factor and high-sensitivity C-reactive protein. We compared the change from baseline parameters in the two groups using Student's t-test or Kruskal-Wallis test. A log-normal multivariate regression analysis was used to adjust for relevant baseline variables. The median reactive hyperaemia index in the vitamin D group increased from 0.65 (interquartile range: 0.42) to 0.73 (interquartile range: 0.36), whereas it decreased from 0.73 (interquartile range: 0.65) to 0.65 (interquartile range: 0.38) (p = 0.02) in the placebo group. After adjustment for baseline variables, the change was not statistically significant for reactive hyperaemia index (p = 0.07) and for other vascular biomarkers (p > 0.05). Targeted vitamin D supplementation for 16 weeks resulted in a small but non-significant improvement in endothelial function in a type 2 diabetes mellitus cohort. PMID- 26818229 TI - Netrin-1 promotes mesenchymal stem cell revascularization of limb ischaemia. AB - This study examines the effect and mechanism of action of Netrin-1 on bone marrow mesenchymal stem cells in angiogenesis. Tube formation and migration of bone marrow mesenchymal stem cells were observed in cell culture. Bone marrow mesenchymal stem cells or Netrin-1-bone marrow mesenchymal stem cells were injected into the ischaemic area of the rat hind limb on the first day after surgery. Laser Doppler perfusion imaging was performed to analyse the levels of vascular endothelial growth factor in plasma and muscles, and immunohistochemistry and immunofluorescence were used to analyse angiogenesis. Bone marrow mesenchymal stem cells in medium containing Netrin-1 markedly increased the number of tubes formed and the migration of bone marrow mesenchymal stem cells compared with the untreated control group. The function of Netrin-1 in tube formation and migration is similar to vascular endothelial growth factor, and combined with vascular endothelial growth factor, Netrin-1 has more enhanced effect than in the other three groups. The Netrin-1-bone marrow mesenchymal stem cell group had better augmented blood-perfusion scores and vessel densities, as well as improved function of the ischaemic limb than that of the group injected with bone marrow mesenchymal stem cells (treated with bone marrow mesenchymal stem cells individually) or the control group (treated with medium). These results suggest that Netrin-1 has the ability to augment the angiogenesis of bone marrow mesenchymal stem cells and improve the function of the ischaemic hind limb by increasing the level of vascular endothelial growth factor. PMID- 26818230 TI - Characterization of the GntR family regulator HpaR1 of the crucifer black rot pathogen Xanthomonas campestris pathovar campestris. AB - The GntR family transcription regulator HpaR1 identified from Xanthomonas campestris pv. campestris has been previously shown to positively regulate the genes responsible for hypersensitive reaction and pathogenicity and to autorepress its own expression. Here, we demonstrated that HpaR1 is a global regulator that positively regulates diverse biological processes, including xanthan polysaccharide production, extracellular enzyme activity, cell motility and tolerance to various stresses. To investigate the regulatory mechanisms of HpaR1, we began with xanthan polysaccharide production, which is governed by a cluster of gum genes. These are directed by the gumB promoter. Disruption of HpaR1 significantly reduced gumB transcription and an electrophoretic mobility shift assay demonstrated that HpaR1 interacts directly with gumB promoter. DNase I footprint analysis revealed that HpaR1 and RNA polymerase were bound to the sequences extending from -21 to +10 and -41 to +29 relative to the transcription initiation site of gumB, respectively. Furthermore, in vitro transcription assays showed that HpaR1 facilitated the binding of RNA polymerase to gumB promoter, leading to an enhancement of its transcription. These results suggest that HpaR1 regulates gumB transcription via a mechanism similar but different to what was found, until now, to only be used by some MerR family transcription activators. PMID- 26818231 TI - Heat-Initiated Chemical Functionalization of Graphene. AB - A heat-initiated chemical reaction was developed to functionalize CVD-grown graphene at wafer scale and the reaction was universally extended to carbon nanotubes, and other precursors that could be thermally converted to active radicals. The chemical reaction can occur in absence of oxygen and water vapor when the temperature is above the decomposition temperature of the reactants. The chemical reaction was also found to be substrate-dependent due to surface doping and inhomogeneity. A large-scale graphene pattern was demonstrated by combing with microfluidic technique. This heat-initiated solid-phase chemical reaction provides a facile and environmentally friendly approach to functionalize carbon nanomaterials with various functional groups. PMID- 26818232 TI - Excitation of coherent propagating spin waves by pure spin currents. AB - Utilization of pure spin currents not accompanied by the flow of electrical charge provides unprecedented opportunities for the emerging technologies based on the electron's spin degree of freedom, such as spintronics and magnonics. It was recently shown that pure spin currents can be used to excite coherent magnetization dynamics in magnetic nanostructures. However, because of the intrinsic nonlinear self-localization effects, magnetic auto-oscillations in the demonstrated devices were spatially confined, preventing their applications as sources of propagating spin waves in magnonic circuits using these waves as signal carriers. Here, we experimentally demonstrate efficient excitation and directional propagation of coherent spin waves generated by pure spin current. We show that this can be achieved by using the nonlocal spin injection mechanism, which enables flexible design of magnetic nanosystems and allows one to efficiently control their dynamic characteristics. PMID- 26818234 TI - Analytical methodology using ion-pair liquid chromatography-tandem mass spectrometry for the determination of four di-ester metabolites of organophosphate flame retardants in California human urine. AB - Alkyl- and aryl-esters of phosphoric acid (both halogenated and non-halogenated) are mainly used as flame retardants (FRs), among other applications, in furniture and consumer products and they are collectively known as organophosphate flame retardants (OPFRs). The absorption, biotransformation or elimination of many of these chemicals in humans and their possible health effects are not yet well known. A major reason for the limited information is the nature of these compounds, which causes several technical difficulties in their isolation and sensitive determination. A novel analytical liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the accurate and sensitive determination of four urinary OPFR metabolites: bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis(2-chloroethyl) phosphate (BCEP), bis(1-chloro-2-propyl) phosphate (BCIPP), and diphenyl phosphate (DPhP), using mixed-mode solid phase extraction and isotope. For the first time all four analytes can be identified in one chromatographic run. An extensive investigation of method development parameters (enzymatic hydrolysis, matrix effects, process efficiency, sources of background interferences, linearity, accuracy, precision, stabilities and limits of detection and quantification) was performed in order to address previously reported method inconsistencies and select a process with the highest accuracy and sensitivity. Chromatographic separation was achieved on a Luna C18 (2) (2.00 mm * 150 mm, 3 MUm) with mobile phase 80:20 v/v water: MeOH and MeOH: water 95:5 v/v, both containing 1mM tributylamine and 1mM acetic acid. Limits of detection were 0.025 ng mL(-1) for BDCIPP and BCIPP and 0.1 ng mL(-1) for DPhP and BCEP. Absolute recoveries of all four analytes and their labeled compounds were in the range of 88-107%. The method was tested on 13 adult California urine samples. BCEP was detected at 0.4-15 ng mL(-1) with a geometric mean (GM): 1.9 ng mL(-1); BDCIPP at 0.5-7.3 ng mL(-1), (GM: 2.5 ng mL(-1)) and DPhP at 0.98) in the range of endogenous concentrations for all studied metabolites. In general, the limits of detection were suitable for the detection of the endogenous levels. Intra- and inter-assay precisions below 25% and accuracies ranging from 80 to 120% were found for most of the analytes. The use of labeled internal standards corrected the moderate matrix effect observed for some compounds. The applicability of the method was confirmed by analyzing urine samples collected from 13 healthy volunteers and comparing the results with previously established normal ranges. In addition, urine samples from two patients and a heterozygous carrier of a family with disturbed monoamine metabolism due to a loss of function mutation in the MAOA gene (X-linked) were analyzed and compared with samples from controls. All data together show the potential of the developed approach for targeted metabolomic studies. PMID- 26818238 TI - Combined chromatography and mass spectrometry for the molecular characterization of food emulsifiers. AB - Food emulsifiers are widely used to stabilise water-fat emulsions such as mayonnaise and dressings. They are prepared by oligomerisation of a poly-alcohol (as e.g. glycerol or citric acid) followed by a reaction with fatty acids. In order to gain insight in the chemical composition of different emulsifiers, a range of chromatographic methods including gas chromatography, size exclusion chromatography, normal phase- and reversed phase liquid chromatography either or not in combination with mass spectrometry was deployed. The different methods turned out to be highly complementary. By combining the information from different methods the polar head group and the fatty acid part of the emulsifier can be characterised in detail. Mass spectrometry is indispensable for establishing the number of polar molecules in the head group as well as for establishing the correct combinations of fatty acids in one molecule. Ten commercial emulsifiers were described at the level of number and type of polar groups and fatty acids present. PMID- 26818239 TI - Evaluation of the phase ratio for three C18 high performance liquid chromatographic columns. AB - For a chromatographic column, phase ratio Phi is defined as the ratio between the volume of the stationary phase Vst and the void volume of the column V0, and it is an important parameter characterizing the HPLC process. Although apparently simple, the evaluation of Phi presents difficulties because there is no sharp boundary between the mobile phase and the stationary phase. In addition, the boundary depends not only on the nature of the stationary phase, but also on the composition of the mobile phase. In spite of its importance, phase ratio is seldom reported for commercially available HPLC columns and the data typically provided by the vendors about the columns do not provide key information that would allow the calculation of Phi based on Vst and V0 values. A different procedure for the evaluation of Phi is based on the following formula: log k'j=a log Kow,j+log Phi, where k'j is the retention factor for a compound j that must be a hydrocarbon, Kow,j is the octanol/water partition coefficient, and a is a proportionality constant. Present study describes the experimental evaluation of Phi based on the measurement of k'j for the compounds in the homologous series between benzene and butylbenzene for three C18 columns: Gemini C18, Luna C18 both with 5 MUm particles, and a Chromolith Performance RP-18. The evaluation was performed for two mobile phase systems at different proportions of methanol/water and acetonitrile/water. The octanol/water partition coefficients were obtained from the literature. The results obtained in the study provide further support for the new procedure for the evaluation of phase ratio. PMID- 26818240 TI - Multi-residue determination of polyhalogenated carbazoles in aquatic sediments. AB - Recent studies have discovered a number of polyhalogenated carbazoles (PHCZs) in aquatic sediments and soil. These substances are attracting emerging concern due to their environmental presence, persistence, and potential dioxin-like activities. In response to the increasing interests in these chemicals, the present study aimed to develop an efficient and sensitive analytical methodology for quantitative determination of environmentally relevant PHCZs in aquatic sediments. The developed method employed time- and solvent-saving extraction and cleanup procedures and utilized gas chromatogram-mass spectrometry (GC-MS) for separation and determination of PHCZ analytes. PHCZs substituted with bromine atom(s) (except for 3-bromocarbazole) or a combination of bromine and chlorine atoms were analyzed by GC-MS in the electron-capture negative ionization (ECNI) mode, whereas congeners substituted with chlorine atoms as well as 3 bromocarbazole were analyzed in electron impact (EI) ionization mode. The developed method demonstrated negligible matrix effects, satisfactory and stable recoveries, and low method limits of quantification (0.11-0.53 ng/g dry weight (dw)) of target analytes. Using this method, we successfully determined a number of PHCZs in surface sediments from the Saginaw River system (Michigan, USA) and the Saginaw Bay of Lake Huron, with the summed concentrations of PHCZ congeners ranging up to 46.3 ng/g dw. Given that further investigations are needed to better elucidate the sources, environmental behavior, fate, and toxicity of PHCZs, highly sensitive and efficient analytical methodologies would be essentially needed to fill in these knowledge gaps. PMID- 26818241 TI - Evaluation of the effects of health impact assessment practice at the local level in Monteregie. AB - BACKGROUND: In Quebec (Canada), the Monteregie Regional Public Health Department has chosen to use health impact assessment (HIA) to support municipalities through a knowledge exchange and collaborative process in order to positively influence decision-making regarding local policies and projects. The value of HIA is becoming increasingly recognized by municipalities interested in planning and managing their cities with an eco-systemic perspective. However, the knowledge and tools which support the use of the HIA at regional and local levels are still missing. METHODS: The general objective is to evaluate the impact the collaborative HIA process used in Monteregie has had on the formulation, adoption and implementation of policies and projects favourable to health. The methodology is based on Mayne's CA design, which allows the identification of factors which contribute to a change process. It is described as one of the best approaches to reduce uncertainty regarding the observed results and the contribution of a program. All of the HIA processes realised between January 2013 and January 2016 in Monteregie will be studied following a case study strategy. Study populations include regional and local public health professionals, municipal officers and community members implicated in these HIAs. Various qualitative and quantitative methods will be used, including examination of documentation, observations on the city grounds, and individual or group interviews. A model of change will be constructed for each HIA process and will present the logical pathway which leads to the observed results, alternative explanations and hypothesises as to why these results were obtained, and contextual factors that could have influenced them. This model will allow the production of a refined contribution story for each HIA. A convergence and divergence analysis will be completed in order to identify differences or similitudes between the different HIAs studied. DISCUSSION: In addition to contributing to the production of knowledge in relation to the collaborative model of HIA, this research project will allow other regional and local public health actors and municipalities of Quebec or other decision-making and political bodies to understand the usefulness of this approach for the improvement of population health and well-being. PMID- 26818242 TI - A network based covariance test for detecting multivariate eQTL in saccharomyces cerevisiae. AB - BACKGROUND: Expression quantitative trait locus (eQTL) analysis has been widely used to understand how genetic variations affect gene expressions in the biological systems. Traditional eQTL is investigated in a pair-wise manner in which one SNP affects the expression of one gene. In this way, some associated markers found in GWAS have been related to disease mechanism by eQTL study. However, in real life, biological process is usually performed by a group of genes. Although some methods have been proposed to identify a group of SNPs that affect the mean of gene expressions in the network, the change of co-expression pattern has not been considered. So we propose a process and algorithm to identify the marker which affects the co-expression pattern of a pathway. Considering two genes may have different correlations under different isoforms which is hard to detect by the linear test, we also consider the nonlinear test. RESULTS: When we applied our method to yeast eQTL dataset profiled under both the glucose and ethanol conditions, we identified a total of 166 modules, with each module consisting of a group of genes and one eQTL where the eQTL regulate the co expression patterns of the group of genes. We found that many of these modules have biological significance. CONCLUSIONS: We propose a network based covariance test to identify the SNP which affects the structure of a pathway. We also consider the nonlinear test as considering two genes may have different correlations under different isoforms which is hard to detect by linear test. PMID- 26818243 TI - Food taboos and myths in South Eastern Nigeria: The belief and practice of mothers in the region. AB - BACKGROUND: Poor nutritional practices especially in pregnancy and early childhood can result in dire consequences in the growth and development of a child. METHODS: This study using purposive sampling enrolled 149 women who had carried at least one pregnancy to term in Enugu south east Nigeria. Logistic regression analysis was used to assess association between avoidance of certain food in pregnancy and selected socio-demographic factors. RESULTS: Approximately 37 % of respondents avoided some foods in pregnancy due to food taboos and no relationship was seen between this avoidance of food and maternal educational attainment, parity (number of obstetrics deliveries) and occupation. Snail and grass-cutter meat were the commonly avoided food in pregnancy while egg were commonly avoided in children under-two years old. Some respondent believed eating snail and grass-cutter meat makes a child sluggish and labour difficult respectively while starting egg early for a child could predispose them to stealing later in life. CONCLUSION: Discussion about food taboos during antenatal care visits and during community education can help reduce the traditional belief about certain food in pregnancy and early childhood. PMID- 26818245 TI - The AIBLHiCoS Method: Predicting Aqueous pKa Values from Gas-Phase Equilibrium Bond Lengths. AB - The proposed AIBLHiCoS method predicts a given compound's pKa in aqueous solution from a single ab initio bond length only, after geometry optimization in the gas phase. Here we provide simple and predictive equations for naphthols and chemically similar biomolecules. Each linear equation corresponds to a High Correlation Subset (HiCoS) that expresses the novel type of linear free energy relationship discovered here. The naphthol family exhibits a clear and strong relationship with the phenol family, with the "active" C-O bond always producing the highest correlations. The proposed method can isolate erroneous experiments and operate in non-aqueous solution and at different temperatures. Moreover, the existence of "active fragments" is demonstrated in a variety of sizable biomolecules for which the pKa is successfully predicted. PMID- 26818244 TI - Feeling Is Believing: Evaluative Conditioning and the Ethics of Pharmaceutical Advertising. AB - A central goal in regulating direct-to-consumer advertising of prescription pharmaceuticals (DTCA) is to ensure that explicit drug claims are truthful. Yet imagery can also alter viewer attitudes, and the degree to which this occurs in DTCA is uncertain. Addressing this data gap, we provide evidence that positive feelings produced by images can promote favourable beliefs about pharmaceuticals. We had participants view a fictitious anti-influenza drug paired with unrelated images that elicited either positive, neutral or negative feelings. Participants who viewed positive images rated the influenza drug as significantly more effective, safe, and beneficial than did participants who viewed negative images. This effect, known as evaluative conditioning, is well described in experimental social psychology but has not previously been shown with pharmaceuticals. We discuss how evaluative conditioning in DTCA may compromise viewer autonomy, and canvass possible regulatory responses. PMID- 26818246 TI - Association between probiotic and yogurt consumption and kidney disease: insights from NHANES. AB - BACKGROUND: Data from experimental animals suggest that probiotic supplements may retard CKD progression. However, the relationship between probiotic use, frequent yogurt consumption (as a natural probiotic source), and kidney parameters have not been evaluated in humans. FINDINGS: We utilized NHANES data, and analyzed the association of probiotic alone (1999-2012) and yogurt/probiotic (2003-2006) use with albuminuria and eGFR after adjustment for demographic and clinical parameters. Frequent yogurt consumption was defined as thrice or more weekly over the year prior to the interview. Frequent yogurt/probiotic consumers had lower adjusted odds of developing combined outcome (albuminuria and/or eGFR < 60 ml/min/1.73 m(2)) compared to infrequent consumers (OR = 0.76; 95 % CI = 0.61 0.94). When evaluated separately, frequent consumers had lower odds of albuminuria and nonsignificant trend towards decreased odds of low eGFR compared to infrequent consumers. In the probiotic cohort, probiotic consumers were found to have a lower adjusted odds of albuminuria compared to nonusers (OR = 0.59; 95 % CI = 0.37-0.94). CONCLUSION: Frequent yogurt and/or probiotics use is associated with decreased odds of proteinuric kidney disease. These hypothesis generating results warrant further translational studies to further delineate the relationship between yogurt/probiotics with kidney dysfunction, as well as microbiome and dysbiosis as potential mediators. PMID- 26818247 TI - Wakayama symposium: role of canonical Notch signaling in conjucntival goblet cell differentiation and dry eye syndrome. AB - This review summarizes a recent finding regarding the intrinsic canonical Notch signaling pathway in regulating normal ocular surface morphogenesis and its role in the pathogenesis of goblet cell deficiency-associated keratoconjunctivitis sicca (KCS, or dry eye). Specifically, we used novel transgenic mice to investigate the mechanism of how the Notch1 activation may serve as the upstream control of expression of transcription factors Kruppel-like factors 4 or 5 (Klf4 or Klf5) which in turn controls goblet cell differentiation and activates mucin 5/ac synthesis during ocular surface morphogenesis. PMID- 26818249 TI - Molecular level insight on the adsorption of carboxylic acids to oxide nanoparticles in aqueous solution by X-ray photoelectron spectroscopy. AB - We show, for the first time, the ability to follow the surface chemistry (acid base equilibrium) of a colloid nanoparticle (AlxOy@SiO2) while simultaneously monitoring the adsorption of a solute molecule (HCOOH) from solution using in situ X-ray photoelectron spectroscopy. Based on the results of the Al 2p and C 1s spectra a mechanism is proposed. PMID- 26818248 TI - Making space for empathy: supporting doctors in the emotional labour of clinical care. AB - BACKGROUND: The academic and medical literature highlights the positive effects of empathy for patient care. Yet, very little attention has been given to the impact of the requirement for empathy on the physicians themselves and on their emotional wellbeing. DISCUSSION: The medical profession requires doctors to be both clinically competent and empathetic towards the patients. In practice, accommodating both requirements can be difficult for physicians. The image of the technically skilful, rational, and emotionally detached doctor dominates the profession, and inhibits physicians from engaging emotionally with their patients and their own feelings, which forms the basis for empathy. This inhibition has a negative impact not only on the patients but also on the physicians. The expression of emotions in medical practice is perceived as unprofessional and many doctors learn to supress and ignore their feelings. When facing stressful situations, these physicians are more likely to suffer from depression and burnout than those who engage with and reflect on their feelings. Physicians should be supported in their emotional work, which will help them develop empathy. Methods could include questionnaires that aid self-reflection, and discussion groups with peers and supervisors on emotional experiences. Yet, in order for these methods to work, the negative image associated with the expression of emotions should be questioned. Also, the work conditions of physicians should improve to allow them to make use of these tools. Empathy should not only be expected from doctors but should be actively promoted, assisted and cultivated in the medical profession. PMID- 26818250 TI - Cerebrospinal fluid inflammatory markers in amnestic mild cognitive impairment. AB - AIMS: Inflammatory processes might play a significant role at the pathophysiology of Alzheimer's disease (AD). Neuroinflammation is characterized by activation of microglia and the release of inflammatory cytokines, such as interleukin (IL) 1beta, IL-6 and tumor necrosis factor-alpha. Although, it is unknown what the real contribution of these inflammatory markers in the development of AD is. The purpose of the present study was to assess the possible relationship between inflammatory markers in the cerebrospinal fluid (CSF) of amnestic mild cognitive impairment patients (aMCI), aged 60 years or older, and compare with aged healthy controls. METHODS: We examined concentrations of IL-1beta, IL-6 and tumor necrosis factor-alpha in the CSF of aMCI patients and controls by enzyme immunoassay. aMCI diagnoses were based on anamnesis and Petersen criteria, corroborated by the Clinical Dementia Rating. Cognitive function was assessed by neuropsychological tests. RESULTS: CSF levels of IL-1beta (13.735 vs 22.932 pg/mL; P < 0.001) and tumor necrosis factor-alpha (1.913 vs 2.627 pg/mL; P = 0.002), but not IL-6 (4.178 vs 5.689 pg/mL; P = 0.106), were significantly reduced in the aMCI samples as compared with controls. Individuals with IL-1beta < 17 pg/mL were at a 7.2 (CI 1.5-36; P: 0.016) increased odds of aMCI. There was a positive correlation between IL-1beta levels and the Consortium to Establish a Registry for Alzheimer's Disease word list score (rs = 0.299; P = 0.046). Linear regression analysis showed that IL-1beta levels might explain 13.7% (beta = 24.545; P = 0.012) of the variance on this Consortium to Establish a Registry for Alzheimer's Disease subscore. CONCLUSION: The present results show a pattern of cytokines expression in the CSF of aMCI patients that might be relevant to the pathogeny of prodromal AD. Geriatr Gerontol Int 2017; 17: 239-245. PMID- 26818251 TI - A Pseudomonas putida double mutant deficient in butanol assimilation: a promising step for engineering a biological biofuel production platform. AB - Biological production in heterologous hosts is of interest for the production of the C4 alcohol (butanol) and other chemicals. However, some hurdles need to be overcome in order to achieve an economically viable process; these include avoiding the consumption of butanol and maintaining tolerance to this solvent during production. Pseudomonas putida is a potential host for solvent production; in order to further adapt P. putida to this role, we generated mini-Tn5 mutant libraries in strain BIRD-1 that do not consume butanol. We analyzed the insertion site of the mini-Tn5 in a mutant that was deficient in assimilation of butanol using arbitrary PCR followed by Sanger sequencing and found that the transposon was inserted in the malate synthase B gene. Here, we show that in a second round of mutagenesis a double mutant unable to take up butanol had an insertion in a gene coding for a multisensor hybrid histidine kinase. The genetic context of the histidine kinase sensor revealed the presence of a set of genes potentially involved in butanol assimilation; qRT-PCR analysis showed induction of this set of genes in the wild type and the malate synthase mutant but not in the double mutant. PMID- 26818252 TI - Recent progress in biobutanol tolerance in microbial systems with an emphasis on Clostridium. AB - Biobased production of butanol promises a more sustainable route for industrial production. However, butanol toxicity remains a barrier for achieving high product titers. Investigation into butanol stress has shed some light on its modes of toxicity. Unfortunately, there still remain significant shortfalls in our understanding of the complex interactions of butanol with cells. To address this knowledge gap, a diverse range of tools have been employed to gain a better understanding of the adverse effects of butanol on the cell. These findings have lead to the identification of possible molecular mechanisms associated with butanol tolerance, which can be harnessed for future strain development efforts. This review focuses on recent efforts to address the toxicity of butanol in microbial producers and offers some perspectives on the future direction of this research sector. PMID- 26818253 TI - Pleiotropic consequences of gene knockouts in the phthiocerol dimycocerosate and phenolic glycolipid biosynthetic gene cluster of the opportunistic human pathogen Mycobacterium marinum. AB - Phthiocerol dimycocerosates (PDIMs) and phenolic glycolipids (PGLs) contribute to the pathogenicity of several mycobacteria. Biosynthesis of these virulence factors requires polyketide synthases and other enzymes that represent potential targets for the development of adjuvant antivirulence drugs. We used six isogenic Mycobacterium marinum mutants, each with a different gene knockout in the PDIM/PGL biosynthetic pathway, to probe the pleiotropy of mutations leading to PDIM(-) PGL(-), PDIM(+) PGL(-) or PDIM(-) PGL(+) phenotypes. We evaluated the M. marinum mutants for changes in antibiotic susceptibility, cell envelope permeability, biofilm formation, surface properties, sliding motility and virulence in an amoeba model. The analysis also permitted us to begin exploring the hypothesis that different gene knockouts rendering the same PDIM and/or PGL deficiency phenotypes lead to M. marinum mutants with equivalent pleiotropic profiles. Overall, the results of our study revealed a complex picture of pleiotropic patterns emerging from different gene knockouts, uncovered unexpected phenotypic inequalities between mutants, and provided new insight into the phenotypic consequences of gene knockouts in the PDIM/PGL biosynthetic pathway. PMID- 26818255 TI - A systematic review of double-bundle versus single-bundle posterior cruciate ligament reconstruction. AB - BACKGROUND: Posterior Cruciate Ligament (PCL) ruptures are common sports injuries. One of the key controversies in PCL reconstruction is whether double bundle reconstruction provides biomechanical and clinical outcomes superior to single-bundle reconstruction. METHODS: We performed a comprehensive search in multiple databases to evaluate the advantages of single-bundle or double bundle reconstructions in anteroposterior stability, graft tension, rotational stability, and functional outcome. RESULTS: Biomechanical comparisons evaluating anteroposterior stability described either no difference or increased stability in double-bundle reconstructions. Comparing these results is complicated by different graft choices, tensioning techniques, and tunnel positions. Biomechanical studies of graft tension demonstrated conflicting results regarding the optimal reconstruction technique. Seven retrospective clinical studies of single- and double-bundle reconstructions with methodological limitations reported no difference in clinical outcome. CONCLUSIONS: The superiority of single-bundle or double-bundle posterior cruciate ligament reconstruction remains uncertain. PMID- 26818256 TI - Human endogenous retroviruses. PMID- 26818254 TI - Developmental nicotine exposure alters cholinergic control of respiratory frequency in neonatal rats. AB - Prenatal nicotine exposure with continued exposure through breast milk over the first week of life (developmental nicotine exposure, DNE) alters the development of brainstem circuits that control breathing. Here, we test the hypothesis that DNE alters the respiratory motor response to endogenous and exogenous acetylcholine (ACh) in neonatal rats. We used the brainstem-spinal cord preparation in the split-bath configuration, and applied drugs to the brainstem compartment while measuring the burst frequency and amplitude of the fourth cervical ventral nerve roots (C4VR), which contain the axons of phrenic motoneurons. We applied ACh alone; the nicotinic acetylcholine receptor (nAChR) antagonist curare, either alone or in the presence of ACh; and the muscarinic acetylcholine receptor (mAChR) antagonist atropine, either alone or in the presence of ACh. The main findings include: (1) atropine reduced frequency similarly in controls and DNE animals, while curare caused modest slowing in controls but no consistent change in DNE animals; (2) DNE greatly attenuated the increase in C4VR frequency mediated by exogenous ACh; (3) stimulation of nAChRs with ACh in the presence of atropine increased frequency markedly in controls, but not DNE animals; (4) stimulation of mAChRs with ACh in the presence of curare caused a modest increase in frequency, with no treatment group differences. DNE blunts the response of the respiratory central pattern generator to exogenous ACh, consistent with reduced availability of functionally competent nAChRs; DNE did not alter the muscarinic control of respiratory motor output. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1138-1149, 2016. PMID- 26818257 TI - Human endogenous retroviruses: friend or foe? AB - The integration of proviral DNA into host chromosomal DNA as an obligatory step in the replication cycle of retroviruses is a natural event of genetic recombination between virus and host. When integration occurs in cells of the germ line, it results in mendelian inheritance of viral sequences that we call endogenous retroviruses (ERV) and HERV for humans. HERVs and host often establish a symbiotic relationship, especially in the placenta and in pluripotent embryonic stem cells, but HERVs occasionally have deleterious consequences for the host. This special issue of APMIS features the fascinating relationships between HERV and humans in health and disease. PMID- 26818258 TI - Viral symbiosis and the holobiontic nature of the human genome. AB - The human genome is a holobiontic union of the mammalian nuclear genome, the mitochondrial genome and large numbers of endogenized retroviral genomes. This article defines and explores this symbiogenetic pattern of evolution, looking at the implications for human genetics, epigenetics, embryogenesis, physiology and the pathogenesis of inborn errors of metabolism and many other diseases. PMID- 26818259 TI - Viruses and the placenta: the essential virus first view. AB - A virus first perspective is presented as an alternative hypothesis to explain the role of various endogenized retroviruses in the origin of the mammalian placenta. It is argued that virus-host persistence is a key determinant of host survival and the various ERVs involved have directly affected virus-host persistence. PMID- 26818260 TI - Expression and function of endogenous retroviruses in the placenta. AB - Although the expression of endogenous retroviruses in the placenta of numerous species was observed a long time ago, their physiological function during gestation was demonstrated only very recently. Expression of retroviral envelope proteins, also called syncytins, in the placenta allows generation of the multinuclear syncytiotrophoblast as an outer cellular layer of the placenta by fusion of the trophoblast cells. This fusion process is crucial for the development of the placenta and for successful pregnancy. It is still unclear whether the immunosuppressive properties of the transmembrane envelope protein of the endogenous retroviruses expressed in the placenta contribute to immunosuppression to prevent the rejection of the semiallotransplant embryo. The presence of placenta cells expressing retroviral envelope proteins surrounded by immune cells deep in the maternal tissue supports an immunosuppressive function. It is important to emphasize that during evolution different species utilized ('enslaved') different endogenous retroviruses and that two or more endogenous retroviruses are involved in placentogenesis in each species. PMID- 26818261 TI - On the classification and evolution of endogenous retrovirus: human endogenous retroviruses may not be 'human' after all. AB - Retroviruses, as part of their replication cycle, become integrated into the genome of their host. When this occurs in the germline the integrated proviruses can become an endogenous retrovirus (ERV) which may eventually become fixed in the population. ERVs are present in the genomes of all vertebrates including humans, where more than 50 groups of human endogenous retrovirus (HERVs) have been described within the last 30 years. Despite state-of-the-art genomic tools available for retroviral discovery and the large number of retroviral sequences described to date, there are still gaps in understanding retroviral macroevolutionary patterns and host-retrovirus interactions and a lack of a coherent systematic classification particularly for HERVs. Here, we discuss the current knowledge on ERV (and HERV) classification, distribution and origins focusing on the role of cross-species transmission in retroviral diversity. PMID- 26818262 TI - Expression and regulation of human endogenous retrovirus W elements. AB - Human endogenous retroviruses (HERV) comprise 8% of the human genome and can be classified into at least 31 families. A typical HERV provirus consists of internal gag, pol and env genes, flanked by two long terminal repeats (LTRs). No single provirus is capable of engendering infectious particles. HERV are by nature repetitive and have with few notable exceptions lost their protein-coding capacity. Therefore, HERV have consistently been excluded from array-based expression studies and hence little is known of their expression, regulation, and potential functional significance. An increasing number of studies have, however, observed expression of the W family of HERV in various human tissues and cells, predominantly in placenta. HERV-W LTRs act as promoters in directing transcription of HERV-W members, contribute to their tissue-specific and highly diversified expression pattern. Furthermore, leaky transcription originating from adjacent genes plays a role in the transcription initiation of HERV-W psudoelements. It has been reported that HERV-W elements, including ERVWE1 (the so far only known HERV-W locus harboring a gene (env) functionally adopted by the human host to critically participate in placenta biogenesis), can become transactivated in a range of human non-placental cell-lines during exogenous virus infections. Aberrant expression of HERV-W has been associated with human diseases, such as cancer, multiple sclerosis, and schizophrenia. Based on published reports, transcriptional activities of HERV-W appear to be influenced by several mechanisms; binding of transcription factors to LTR promoters and enhancers outside of LTRs, genetic variation and alteration in DNA methylation and histone modification. Emerging mechanistic studies support the notion that HERV-W represents a potential marker or mediator of environmental exposures (e.g., virus infection) in the development of chronic complex diseases. PMID- 26818263 TI - HERV-K(HML-2), a seemingly silent subtenant - but still waters run deep. AB - A large proportion of the human genome consists of endogenous retroviruses, some of which are well preserved, showing transcriptional activity, and expressing retroviral proteins. The HERV-K(HML-2) family represents the most intact members of these elements, with some having open and intact reading frames for viral proteins and the ability to form virus-like particles. Although generally suppressed in most healthy tissues by a variety of epigenetic processes and antiviral mechanisms, there is evidence that some members of this family are (at least partly) still active - particularly in certain stem cells and various tumors. This raises the possibility of their involvement in tumor induction or in developmental processes. In recent years, many new insights into this fascinating field have been attained, and this review focuses on new discoveries about coevolutionary events and intracellular defense mechanisms against HERV-K(HML-2) activity. We also describe what might occur when these mechanisms fail or become modulated by viral proteins or other viruses and discuss the new vistas opened up by the reconstitution of ancestral viral proteins and even complete HML-2 viruses. PMID- 26818264 TI - The role of molecular mimicry and other factors in the association of Human Endogenous Retroviruses and autoimmunity. AB - Human Endogenous Retroviruses (HERVs) have been implicated in autoimmune and other diseases. Molecular mimicry has been postulated as a potential mechanism of autoimmunity. Exogenous viruses have also been reported to be associated with the same diseases, as have genetic and environmental factors. If molecular mimicry were to be shown to be an initiating mechanism of some autoimmune diseases, then therapeutic options of blocking antibodies and peptides might be of benefit in halting diseases at the outset. Bioinformatic and molecular modelling techniques have been employed to investigate molecular mimicry and the evidence for the association of HERVs and autoimmunity is reviewed. The most convincing evidence for molecular mimicry is in rheumatoid arthritis, where HERV K-10 shares amino acid sequences with IgG1Fc, a target for rheumatoid factor. Systemic lupus erythematosus is an example of a condition associated with several autoantibodies, and several endogenous and exogenous viruses have been reported to be associated with the disease. The lack of a clear link between one virus and this condition, and the spectrum of clinical manifestations, suggests that genetic, environmental and the inflammatory response to a virus or viruses might also be major factors in the pathogenesis of lupus and other autoimmune conditions. Where there are strong associations between a virus and an autoimmune condition, such as in hepatitis C and cryoglobulinaemia, the use of bioinformatics and molecular modelling can also be utilized to help to understand the role of molecular mimicry in how HERVs might trigger disease. PMID- 26818265 TI - The role of human endogenous retroviruses in brain development and function. AB - Endogenous retroviral sequences are spread throughout the genome of all humans, and make up about 8% of the genome. Despite their prevalence, the function of human endogenous retroviruses (HERVs) in humans is largely unknown. In this review we focus on the brain, and evaluate studies in animal models that address mechanisms of endogenous retrovirus activation in the brain and central nervous system (CNS). One such study in mice found that TRIM28, a protein critical for mouse early development, regulates transcription and silencing of endogenous retroviruses in neural progenitor cells. Another intriguing finding in human brain cells and mouse models was that endogenous retrovirus HERV-K appears to be protective against neurotoxins. We also report on studies that associate HERVs with human diseases of the brain and CNS. There is little doubt of an association between HERVs and a number of CNS diseases. However, a cause and effect relationship between HERVs and these diseases has not yet been established. PMID- 26818266 TI - Human endogenous retroviruses in neurologic disease. AB - Endogenous retroviruses are pathogenic - in other species than the human. Disease associations for Human Endogenous RetroViruses (HERVs) are emerging, but so far an unequivocal pathogenetic cause-effect relationship has not been established. A role for HERVs has been proposed in neurological and neuropsychiatric diseases as diverse as multiple sclerosis (MS) and schizophrenia (SCZ). Particularly for MS, many aspects of the activation and involvement of specific HERV families (HERV H/F and HERV-W/MSRV) have been reported, both for cells in the circulation and in the central nervous system. Notably envelope genes and their gene products (Envs) appear strongly associated with the disease. For SCZ, for ALS, and for HIV associated dementia (HAD), indications are accumulating for involvement of the HERV-K family, and also HERV-H/F and/or HERV-W. Activation is reasonably a prerequisite for causality as most HERV sequences remain quiescent in non pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, derepression, and also involvement of retroviral restriction factors, is emerging. HERV-directed antiretrovirals have potential as novel therapeutic paradigms in neurologic disease, particularly in MS. The possible protective or ameliorative effects of antiretroviral therapy in MS are substantiated by reports that treatment of HIV infection may be associated with a significantly decreased risk of MS. Further studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are essential. PMID- 26818267 TI - Utility of next-generation RNA-sequencing in identifying chimeric transcription involving human endogenous retroviruses. AB - Several studies have shown that human endogenous retroviruses and endogenous retrovirus-like repeats (here collectively HERVs) impose direct regulation on human genes through enhancer and promoter motifs present in their long terminal repeats (LTRs). Although chimeric transcription in which novel gene isoforms containing retroviral and human sequence are transcribed from viral promoters are commonly associated with disease, regulation by HERVs is beneficial in other settings; for example, in human testis chimeric isoforms of TP63 induced by an ERV9 LTR protect the male germ line upon DNA damage by inducing apoptosis, whereas in the human globin locus the gamma- and beta-globin switch during normal hematopoiesis is mediated by complex interactions of an ERV9 LTR and surrounding human sequence. The advent of deep sequencing or next-generation sequencing (NGS) has revolutionized the way researchers solve important scientific questions and develop novel hypotheses in relation to human genome regulation. We recently applied next-generation paired-end RNA-sequencing (RNA-seq) together with chromatin immunoprecipitation with sequencing (ChIP-seq) to examine ERV9 chimeric transcription in human reference cell lines from Encyclopedia of DNA Elements (ENCODE). This led to the discovery of advanced regulation mechanisms by ERV9s and other HERVs across numerous human loci including transcription of large gene unannotated genomic regions, as well as cooperative regulation by multiple HERVs and non-LTR repeats such as Alu elements. In this article, well-established examples of human gene regulation by HERVs are reviewed followed by a description of paired-end RNA-seq, and its application in identifying chimeric transcription genome-widely. Based on integrative analyses of RNA-seq and ChIP-seq, data we then present novel examples of regulation by ERV9s of tumor suppressor genes CADM2 and SEMA3A, as well as transcription of an unannotated region. Taken together, this article highlights the high suitability of contemporary sequencing methods in future analyses of human biology in relation to evolutionary acquired retroviruses in the human genome. PMID- 26818268 TI - Dynamic and selective HERV RNA expression in neuroblastoma cells subjected to variation in oxygen tension and demethylation. AB - We studied HERV expression in cell lines after hypoxia, mitogenic stimulation, and demethylation, to better understand if hypoxia may play a role in ERV activation also within the nervous system, as represented by neuroblastoma cell lines. The level of RNA of four human ERV groups (HERVs) (HERVE, I/T, H, and W), and three housekeeping genes, of different cell lines including A549, COS-1, Namalwa, RD-L and Vero-E6, as well as human neuroblastoma cell lines SH-SY5Y, SK N-DZ, and SK-N-AS were studied using reverse transcription and real-time quantitative PCR (QPCR). During the course of recovery from hypoxia a pronounced and selective activation of RNA expression of HERVW-like sequences, but not of HERVE, I/T, H, and three housekeeping genes, was found in the neuroblastoma cell lines, most pronounced in SK-N-DZ. In the SK-N-DZ cell line, we also tested the expression of HERVs after chemical treatments. HERVW-like sequences were selectively upregulated by 5-azacytidine, a demethylating agent. Some HERVW loci seem especially responsive to hypoxia and demethylation. HERV expression in neuroblastoma cells is selectively and profoundly influenced by some physiological and chemical stimuli. PMID- 26818269 TI - Marker assisted pyramiding of drought yield QTLs into a popular Malaysian rice cultivar, MR219. AB - BACKGROUND: Three drought yield QTLs, qDTY 2.2, qDTY 3.1, and qDTY 12.1 with consistent effect on grain yield under reproductive stage drought stress were pyramided through marker assisted breeding with the objective of improving the grain yield of the elite Malaysian rice cultivar MR219 under reproductive stage drought stress. Foreground selection using QTL specific markers, recombinant selection using flanking markers, and background selection were performed. BC1F3 derived lines with different combinations of qDTY 2.2 , qDTY 3.1, and qDTY 12.1 were evaluated under both reproductive stage drought stress and non-stress during the dry seasons of 2013 and 2014 at IRRI. RESULTS: The grain yield reductions in the stress trials compared to non-stress trials ranged from 79 to 93%. In the stress trials, delay in days to flowering and reduction in plant height were observed. In both seasons, MR219 did not produce any yield under stress, however it produced a yield of 5917 kg ha(-1) during the 2013 dry season and 8319 kg ha( 1) during the 2014 dry season under non-stress. Selected introgressed lines gave a yield advantage of 903 to 2500 kg ha(-1) over MR219 under reproductive stage drought stress and a yield of more than 6900 kg ha(-1) under non-stress during the 2014 dry season. Among lines with single qDTY, lines carrying qDTY 2.2 provided a higher yield advantage under reproductive stage drought stress in the MR219 background. Two-qDTY combinations (qDTY 3.1+ qDTY 2.2 and qDTY 3.1+ qDTY 12.1) performed better than lines with three qDTY combinations, indicating the absence of positive interactions between the three qDTYs. CONCLUSION: We successfully developed drought-tolerant MR219 pyramided lines with a yield advantage of more than 1500 kg ha(-1). Differential yield advantages of different combinations of the qDTYs indicate a differential synergistic relationship among qDTYs. This is the first report on the successful effect of qDTYs in increasing the yield under drought in genetic backgrounds other than those in which the qDTYs were earlier identified. PMID- 26818270 TI - Lipofilling of the Breast Does Not Increase the Risk of Recurrence of Breast Cancer: A Matched Controlled Study. AB - BACKGROUND: Although many plastic surgeons perform autologous fat grafting (lipofilling) for breast reconstruction after oncologic surgery, it has not been established whether postoncologic lipofilling increases the risk of breast cancer recurrence. The authors assessed the risk of locoregional and systemic recurrence in patients who underwent lipofilling for breast reconstruction. METHODS: The authors identified all patients who underwent segmental or total mastectomy for breast cancer (719 breasts) (i.e., cases) or breast cancer risk reduction or benign disease (305 cancer-free breasts) followed by breast reconstruction with lipofilling as an adjunct or primary procedure between June of 1981 and February of 2014. They also then identified matched patients with breast cancer treated with segmental or total mastectomy followed by reconstruction without lipofilling (670 breasts) (i.e., controls). The probability of locoregional recurrence was estimated by the Kaplan-Meier method. RESULTS: Mean follow-up times after mastectomy were 60 months for cases, 44 months for controls, and 73 months for cancer-free breasts. Locoregional recurrence was observed in 1.3 percent of cases (nine of 719 breasts) and 2.4 percent of controls (16 of 670 breasts). Breast cancer did not develop in any cancer-free breast. The cumulative 5-year locoregional recurrence rates were 1.6 percent and 4.1 percent for cases and controls, respectively. Systemic recurrence occurred in 2.4 percent of cases and 3.6 percent of controls (p = 0.514). There was no primary breast cancer in healthy breasts reconstructed with lipofilling. CONCLUSIONS: The study results showed no increase in locoregional recurrence, systemic recurrence, or second breast cancer. These findings support the oncologic safety of lipofilling in breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II. PMID- 26818271 TI - A Comparison of Methods to Assess Mastectomy Flap Viability in Skin-Sparing Mastectomy and Immediate Reconstruction: A Prospective Cohort Study. AB - BACKGROUND: Skin-sparing mastectomy with immediate reconstruction can yield excellent aesthetic results, but high rates of mastectomy flap necrosis have been reported. A prospective cohort study was undertaken to compare three methods of assessing mastectomy flap viability following skin-sparing mastectomy and immediate reconstruction to determine which is most effective in reducing mastectomy flap necrosis. METHODS: The study group included 60 consecutive patients (99 breasts) undergoing skin-sparing mastectomy and immediate reconstruction with either tissue expanders (n = 39) or transverse rectus abdominis musculocutaneous flaps (n = 21). Mastectomy flap viability was assessed either visually (n = 20), with fluorescein dye and Wood's lamp imaging (n = 20), or by indocyanine green angiography (n = 20). Variation across groups was analyzed using analysis of variance for continuous variables and chi-square test for dichotomous variables. RESULTS: The mean follow-up was 10 months. There were no significant differences in mean age, body mass index, medical history, smoking history, pathologic diagnosis, chemotherapy, or reconstruction type. Mastectomy flap necrosis was observed in eight of 30 breasts in the direct visualization group (27 percent), compared with 14 percent in the indocyanine green angiography group and 3 percent in the fluorescein group (p = 0.03). The reoperation rate in the direct visualization group was 20 percent, compared with 15 percent in the indocyanine green angiography group and 0 percent in the fluorescein group. CONCLUSIONS: Fluorescein dye was associated with the lowest rate of complications after skin-sparing mastectomy, but indocyanine green angiography was also shown to reduce mastectomy flap necrosis compared with direct visualization. Routine imaging of mastectomy flap perfusion seems to be beneficial in skin-sparing mastectomy, but intravenous fluorescein may be as effective as more expensive modalities. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II. PMID- 26818272 TI - Discussion: A Comparison of Methods to Assess Mastectomy Flap Viability in Skin Sparing Mastectomy and Immediate Reconstruction: A Prospective Cohort Study. PMID- 26818274 TI - Perioperative Optimization of Autologous Breast Reconstruction. AB - The authors recently showed that fast-track surgery could reduce the length of stay after a deep inferior epigastric perforator flap procedure from 7.4 days to 6.2 days without increasing complication rates or flap loss. This study improves the protocol and identifies specific factors that kept patients in the hospital. The authors present their results from the first 16 consecutive cases. Multimodal opioid-sparing analgesia was used. Nurses removed suction drains, without consulting the doctors. Fulfillment of functional discharge criteria (e.g., flap monitoring, ambulation) was assessed twice daily, and specified reasons for not allowing discharge were registered. All patients were discharged to home after approximately 72 hours, on the third postoperative day, except one patient who was discharged on day 4. Drains were removed on postoperative day 2 (n = 3) or 3 (n = 13). All patients had normal gastrointestinal tract function and minimal pain, and were eating and managing personal hygiene on the morning of postoperative day 2. All were mobilized by the afternoon of postoperative day 2. Median visual analogue scale score at discharge was 1 (range, 0 to 4). There were no reoperations and no major complications. Length of stay after autologous breast reconstruction using deep inferior epigastric perforator flaps can be reduced to approximately 3 days using the fast-track methodology. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 26818273 TI - Surgical Timing and the Menstrual Cycle Affect Wound Healing in Young Breast Reduction Patients. AB - BACKGROUND: Young female subjects are known to have the highest baseline menstrual hormone levels of any female age group. Studies have found an association between hormone levels and wound healing. This has been researched in the orthopedic, gynecologic, and dermatologic literature, and more recently, in young patients undergoing augmentation mammaplasty. The purpose of this study was to determine whether the timing of surgery relative to the menstrual cycle plays a role in surgical complications following bilateral reduction mammaplasty. METHODS: All female patients aged 25 years or younger with a documented last menstrual cycle undergoing a bilateral reduction mammaplasty from 2005 to 2013 were reviewed. Surgical timing and postoperative complications relative to the last menstrual cycle were recorded. The preovulatory phase referred to days 1 to 14 after the patient's last menstrual cycle, whereas the postovulatory phase referred to days 15 to 28. RESULTS: Forty-nine patients met inclusion criteria. Undergoing bilateral reduction mammaplasty during the postovulatory phase was associated with development of wound dehiscence and hypertrophic scarring (p < 0.005), which were the most common postoperative complications. Surgery in the preovulatory or postovulatory phase did not affect hematoma, seroma, wound infection, or nipple-areolar complex necrosis rates (p > 0.05). Age, race/ethnicity, body mass index, large resection mass, and medical comorbidities did not affect wound dehiscence or scar hypertrophy rates (p > 0.05). CONCLUSIONS: Young patients undergoing bilateral reduction mammaplasty during the postovulatory phase of the menstrual cycle have an increased risk of wound healing issues and poor scarring. This may be attributable to hormonal fluxes occurring during this phase and the already high hormone levels in this population. PMID- 26818275 TI - Bioengineered Breast: Concept, Technique, and Preliminary Results. AB - Breasts reconstructed with implants, following mastectomy, lack the soft-tissue envelope of natural breasts. Further implant-related complications such as implant visibility, rippling/wrinkling, and/or hollowing/depression of the skin that often appear in the vicinity of the upper pole may be attributed to soft tissue deficits. To address these shortcomings, the authors have developed the "bioengineered breast" concept that uses a combination of biological matrix and/or autologous fat grafting at the upper pole to augment the soft-tissue volume of breasts at the second stage of a two-stage breast reconstruction procedure. Enhancing the soft-tissue cover not only supplements volume and shape but further alters how the recipient's host tissue responds to the foreign body implant. The authors have used the bioengineered breast concept in over 500 reconstructions, with good outcomes and low complication rates. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID- 26818276 TI - Long-Term Results and Refinement of the Turkish Delight Technique for Primary and Secondary Rhinoplasty: 25 Years of Experience. AB - BACKGROUND: All grafts present the potential problem of late visibility, distortion, and (occasionally) absorption. To overcome these problems and obtain a smoother surface, in 1989, the author initiated the use of finely diced cartilage wrapped in Surgicel. It is well known that the resolution of edema at the end of 1 year postoperatively is approximately 90 to 95 percent. Complete resolution continues until the end of 4 years postoperatively. However, it is important to understand what occurs beyond 4 years, and how the nose changes as the face ages. METHODS: The author presents his experience of the past 25 years on 9398 primary and secondary rhinoplasty patients treated using his personal approach, the Turkish delight. Patients with a postoperative range from 4 to 25 years were selected. RESULTS: The Turkish delight type of cartilage graft (diced cartilage wrapped in Surgicel) has been free of late show complications often experienced with other types of tip grafts. Long-term results from 4 to 25 years are very satisfactory, with an acceptably low complication rate. CONCLUSIONS: This technique is safe, reliable, effective, simple, and easily applicable by plastic surgeons at all levels of experience. Early and long-term results from 1 to 25 years are very satisfactory. The overall complication rate is very low compared with other techniques. In addition, there is no late show as is sometimes seen with other types of cartilage grafts such as crushed, oval, or rectangular grafts. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 26818277 TI - Full Facial Feminization Surgery: Patient Satisfaction Assessment Based on 180 Procedures Involving 33 Consecutive Patients. AB - BACKGROUND: Gender dysphoria refers to the discomfort and distress that arise from a discrepancy between a person's gender identity and sex assigned at birth. The treatment plan for gender dysphoria varies and can include psychotherapy, hormone treatment, and gender reassignment surgery, which is, in part, an irreversible change of sexual identity. Procedures for transformation to the female sex include facial feminization surgery, vaginoplasty, clitoroplasty, and breast augmentation. Facial feminization surgery can include forehead remodeling, rhinoplasty, mentoplasty, thyroid chondroplasty, and voice alteration procedures. Described here is an assessment of patient satisfaction after facial feminization surgery, including outcome measurements after forehead slippage and chin remodeling. METHODS: Thirty-three patients between 19 and 40 years of age were referred for facial feminization surgery between January of 2003 and December of 2013, for a total of 180 procedures. Surgical outcome was analyzed both subjectively through questionnaires administered to patients and objectively by serial photographs. RESULTS: Most facial feminization surgery procedures can be safely completed in 6 months, barring complications. All patients showed excellent cosmetic results and were satisfied with their procedures. Both frontal and profile views achieved a loss of masculine features. CONCLUSIONS: Patient satisfaction after facial feminization surgery is high. The reduction of gender dysphoria has psychological and social benefits and significantly affects patient outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 26818278 TI - Discussion: Full Facial Feminization Surgery: Patient Satisfaction Assessment Based on 180 Procedures Involving 33 Consecutive Patients. PMID- 26818279 TI - Cosmetic Body Lift. AB - BACKGROUND: High-tension lateral abdominoplasty provides ideal central contouring of the abdomen, but it inadequately addresses laxity and fullness in the flank and lateral thigh. The adjunct of liposuction improves abdomen contour, but excess flank soft tissue often persists. Small case series in the literature have suggested an extended abdominoplasty to address these deficits with variable outcomes. The senior author (S.T.H.) reports his successes in the largest series to date of a 270-degree extended lipoabdominoplasty (cosmetic body lift) for non massive weight loss patients to optimally contour the abdomen, hips, and flanks while lifting the lateral thigh and reducing thigh circumference. METHODS: A retrospective chart review was conducted on patients who had a cosmetic body lift between 2004 and 2014. On average, outcomes were reviewed 1 year postoperatively. RESULTS: From 2004 to 2014, 72 consecutive patients (one male patient) with an average age of 53 years (range, 33 to 73 years) had a cosmetic body lift. All patients were nonsmokers and had insignificant preoperative comorbidities. Average total liposuction volume was 3067 cc. Complications included seroma in 2.8 percent (two of 72), infection in 4.2 percent (three of 72), delayed wound healing in 5.6 percent (four of 72), necrosis/ischemia in 4.2 percent (three of 72), revision in 18.1 percent (13 of 72), and deep vein thrombosis in 1.4 percent (one of 72), with zero hematomas. CONCLUSIONS: This investigation is the largest series to date to evaluate the cosmetic body lift for the non-massive weight loss population. Consistent with reported complication rates of lipoabdominoplasty in the literature, the cosmetic body lift is a safe and effective operation for optimal waist contouring. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 26818280 TI - Body Dysmorphic Disorder in Patients Seeking Abdominoplasty, Rhinoplasty, and Rhytidectomy. AB - BACKGROUND: Body dysmorphic disorder may negatively affect self-perception of body shape and lead patients to seek cosmetic surgery. This study estimates the level of body dissatisfaction and prevalence of body dysmorphic disorder symptoms in candidates for three plastic surgical procedures. METHODS: Three hundred patients of both sexes divided into three groups (abdominoplasty, n = 90; rhinoplasty, n =151; and rhytidectomy, n =59) were classified as having (n =51, n =79, and n =25, respectively) or not having (n =39, n =72, and n =34, respectively) body dysmorphic disorder symptoms, based on the Body Dysmorphic Disorder Examination, which was administered preoperatively. RESULTS: Prevalence rates of body dysmorphic disorder symptoms in the abdominoplasty, rhinoplasty, and rhytidectomy groups were 57, 52, and 42 percent, respectively. Significant between-group differences were observed regarding age (p < 0.001), body mass index (p = 0.001), and onset of body dysmorphic disorder symptoms (p < 0.001). Within-group differences in body dysmorphic disorder severity were observed in the abdominoplasty (p < 0.001), rhinoplasty (p < 0.001), and rhytidectomy (p = 0.005) groups. Body dysmorphic disorder severity was significantly associated with degree of body dissatisfaction (mean Body Dysmorphic Disorder Examination total scores; p < 0.001), avoidance behaviors (p< 0.001), sexual abuse (p = 0.026), suicidal ideation (p < 0.001), and suicide attempt (p = 0.012). CONCLUSIONS: Abdominoplasty candidates showed the highest prevalence; rhytidectomy candidates exhibited the highest percentage of severe cases, and rhinoplasty candidates had the lowest percentage of severe cases. PMID- 26818281 TI - Aspiration of Periprosthetic Seromas Using the Blunt SeromaCath. AB - Postoperative swelling following prosthetic implant breast augmentation and reconstruction is not uncommon. Prompt diagnosis and targeted treatment are critical. Current treatment recommendations achieve a diagnosis using specialized equipment with needle-guided imaging and/or surgical modalities. These techniques are expensive and delay diagnosis and treatment. The authors use an in-office, nonimaging technique to drain periprosthetic fluid after unilateral breast swelling after breast reconstruction or augmentation. Their technique is effective in diagnosing and treating seroma fluid with minimal risk of implant damage or perforation. PMID- 26818282 TI - The Importance of the Upper Lateral Cartilage in Rhinoplasty. AB - The upper lateral cartilages are instrumental in obtaining optimal outcomes in aesthetic and functional rhinoplasty. Knowledgeable manipulation of the upper lateral cartilages can take advantage of the crucial malleable parameters of projection, width, nasal dorsal shape, and tip rotation. A lucid understanding of the anatomical intricacies in this portion of the cartilaginous framework permits the surgeon to use their unique characteristics to consistently achieve the desired results. PMID- 26818283 TI - Celebrating the Fiftieth Baker Gordon Symposium on Cosmetic Surgery: The Legacy of Thomas J. Baker, M.D. AB - The Baker Gordon Symposium on Cosmetic Surgery celebrates its fiftieth year. A review of its history mirrors the evolution of aesthetic surgery in terms of advancements in techniques, and the acceptance of cosmetic surgery as a credible subspecialty of plastic surgery. Beginning in 1967, the Baker Gordon Symposium was the first live surgery symposium that focused on aesthetic surgery, and set a precedent for aesthetic surgery education over the ensuing decades. Historically, the pioneers in aesthetic techniques first presented their innovations at the Baker Gordon Symposium, helping to educate and train their peers to perform cosmetic procedures. The legacy of Thomas Baker is intertwined with the history of the Baker Gordon Symposium, both in terms of his contributions to plastic surgery education, and to the acceptance of the subspecialty of aesthetic surgery. PMID- 26818284 TI - Transplantation of an LGR6+ Epithelial Stem Cell-Enriched Scaffold for Repair of Full-Thickness Soft-Tissue Defects: The In Vitro Development of Polarized Hair Bearing Skin. AB - BACKGROUND: Recent literature has shown that full-thickness wounds, devoid of the stem cell niche, can subsequently be reconstructed with functional skin elements following migration of the LGR6 epithelial stem cell into the wound bed. In this study, the authors use a variety of LGR6 epithelial stem cell-seeded scaffolds to determine therapeutic utility and regenerative potential in the immediate reconstruction of full-thickness wounds. METHODS: Isolated LGR6 epithelial stem cells were seeded onto a spectrum of acellular matrices and monitored in both in vitro and in vivo settings to determine their relative capacity to regenerate tissues and heal wounds. RESULTS: Wound beds containing LGR6 stem cell-seeded scaffolds showed significantly augmented rates of healing, epithelialization, and hair growth compared with controls. Gene and proteomic expression studies indicate that LGR6 stem cell-seeded constructs up-regulate WNT, epidermal growth factor, and angiogenesis pathways. Finally, the addition of stromal vascular fraction to LGR6 stem cell-seeded constructs induces polarized tissue formation, nascent hair growth, and angiogenesis within wounds. CONCLUSIONS: LGR6 stem cells are able to undergo proliferation, differentiation, and migration following seeding onto a variety of collagen-based scaffolding. In addition, deployment of these constructs induces epithelialization, hair growth, and angiogenesis within wound beds. The addition of stromal vascular fraction to LGR6 stem cell containing scaffolds initiated an early form of tissue polarization, providing for the first time a clinically applicable stem cell-based construct that is capable of the repair of full-thickness wounds and hair regeneration. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID- 26818285 TI - Discussion: Transplantation of an LGR6+ Epithelial Stem Cell-Enriched Scaffold for Repair of Full-Thickness Soft-Tissue Defects: The In Vitro Development of Polarized Hair-Bearing Skin. PMID- 26818286 TI - Thioredoxin Protects Skin Flaps from Ischemia-Reperfusion Injury: A Novel Prognostic and Therapeutic Target. AB - BACKGROUND: Ischemia-reperfusion injury is inevitable during free-tissue transfer, causing oxidative damage and extensive apoptosis. Thioredoxin is an endogenous protein with antioxidant and antiapoptotic activity in a variety of tissues. This study aims to investigate the protective effects of human thioredoxin-1 on ischemia-reperfusion flaps, and its clinical application value. METHODS: Sixteen clinical specimens of ischemia-reperfusion flaps were collected and assessed for apoptosis and thioredoxin-1 expression. Eighty mice were administered recombinant human thioredoxin-1 or saline intraperitoneally for 5 days before ischemia-reperfusion. Half of the mice were killed 24 hours after reperfusion. The flap tissues were harvested and detected for the changes of morphology, apoptosis, redox condition, and relative protein expression. The flap survival percentage of the remaining mice was consecutively observed within 7 days of reperfusion. RESULTS: Thioredoxin-1 abundance was negatively correlated with ischemia-reperfusion-induced apoptosis in human samples and animal models. The survival rate of the ischemia-reperfusion flaps in mice increased significantly following recombinant human thioredoxin-1 pretreatment. Mitigated tissue damage, reduced apoptosis, and more antioxidant activity were observed in recombinant human thioredoxin-1-pretreated flaps. Western blot analysis revealed thioredoxin-1 depletion and a significant increase in apoptosis signal-regulating kinase 1, p-p38, and cleaved caspase-3 abundance in the ischemia-reperfusion flaps, whereas supplementation of recombinant human thioredoxin-1 significantly reduced the apoptosis-related protein expression. CONCLUSIONS: Thioredoxin-1 exerts its flap-protective role through redox regulation of reactive oxygen species scavenging and antiapoptotic signaling. The authors' research provides evidence that thioredoxin-1 may serve as a potential prognostic and therapeutic target for skin flap ischemia-reperfusion injury. PMID- 26818287 TI - Novel Atraumatic End-to-Side Repair Model Exhibits Robust Collateral Sprouting Independent of Donor Fiber Injury. AB - BACKGROUND: A central issue underlying end-to-side neurorrhaphy technique is whether injury to the donor nerve fibers is necessary for successful reinnervation of the recipient nerve. To address this question, the authors developed a novel atraumatic end-to-side neurorrhaphy model that uses the preexisting anatomical structure of the median nerve as the Y-chamber to study the mechanism of collateral sprouting. METHODS: In this rat forelimb model, the authors transected the musculocutaneous nerve and the lateral head of the median nerve, and coapted their distal stumps together. In this model, the authors use the medial head of the median nerve as the donor nerve, and the lateral head of the median nerve (distal stump) as a Y-shaped chamber, which provided structural connection to the recipient musculocutaneous nerve in end-to-side fashion. RESULTS: Three months after surgery, converging histologic, electrophysiologic, and behavioral observations confirmed the successful reinnervation of the recipient nerve. Retrograde labeling indicated that sensory fibers exhibited greater collateral sprouting than observed for motor fibers. Interestingly, fluorescence of these collateral sprouting fibers was present only when the median nerve lateral head was attached to the musculocutaneous nerve of the biceps, indicating that factors derived from the denervated tissue likely induced the collateral sprouting in this model. CONCLUSIONS: The authors' findings provide strong evidence that collateral sprouting can be robustly initiated independent of donor nerve fiber injury. The authors' model can accelerate the understanding of the mechanism underlying end-to-side neurorrhaphy and the optimization of its clinical use. PMID- 26818288 TI - Topical Administration of Oxygenated Hemoglobin Improved Wound Healing in an Ischemic Rabbit Ear Model. AB - BACKGROUND: Localized oxygen deficiency plays a central role in the pathogenesis of chronic wounds; thus, rectifying localized ischemia with oxygen therapy has been postulated to be an integral aspect of the management of chronic wounds. The efficacy of a novel approach for oxygen therapy on chronic wound healing was evaluated. METHODS: Oxygen was delivered to ischemic wounds by means of the topical application of oxygenated, chemically modified bovine hemoglobin (IKOR 2084) in a validated rabbit ear ischemic wound model. The wound healing was evaluated histologically by measuring epithelial gap and neo-granulation tissue area. In situ expression of endothelial cells (CD31) and proliferative cells (Ki 67) was examined by immunohistochemistry analysis. The mRNA of vascular endothelial growth factor, endothelial nitric oxide synthase, and matrix metalloproteinase-9 was quantified by real-time reverse-transcriptase polymerase chain reaction. The collagen was detected by Sirius red staining. RESULTS: In comparison with topical application of saline, the administration of oxygenated IKOR 2084 increases wound reepithelialization and formation of neo-granulation tissue in a dose-dependent manner, and cellular proliferation (Ki-67). Conversely, the administration of deoxygenated IKOR 2084 aggravated the ischemic wound healing process. Moreover, the topical administration of oxygenated IKOR 2084 induces angiogenesis as evidenced by concomitant increases in CD31 protein and vascular endothelial growth factor and endothelial nitric oxide synthase mRNA expression in treated wounds. Oxygenated IKOR 2084 administration also increased collagen deposition in wounds, with decreases in the expression of matrix metalloproteinase-9 mRNA. CONCLUSION: This study suggests that the topical application of oxygenated IKOR 2084 ameliorates the reparative progress of ischemic wounds through enhanced angiogenesis, cellular proliferation, and collagen deposition. PMID- 26818289 TI - Sutureless Microsurgical Anastomosis Using an Optimized Thermoreversible Intravascular Poloxamer Stent. AB - BACKGROUND: Sutureless microvascular anastomosis has great translational potential to simplify microvascular surgery, shorten operative times, and improve clinical outcomes. The authors developed a transient thermoreversible microvascular stent using a poloxamer to maintain vessel lumen patency before application of commercially available adhesives to seal the anastomosis instead of sutures. Despite technical success, human application necessitates bovine serum albumin removal from existing formulations; rapid poloxamer transition between states; and increased stiffness for reliable, reproducible, and precise microvascular approximation. METHODS: Two commercially available poloxamers were used in this study (P407 and P188). After removing bovine serum albumin, each poloxamer was tested at varying concentrations either alone or in combination to determine the optimal preparation for sutureless microvascular anastomosis. Transition temperature and formulation stiffness were tested in vitro by rheometry, with the most promising combinations tested in an established in vivo model. RESULTS: Increasing poloxamer concentration resulted in an increase in stiffness and decrease in transition temperature. Pure P188 without bovine serum albumin, dissolved in phosphate-buffered saline to a 45% concentration, demonstrated desirable rheologic behavior, with precise gel transition and increased gel stiffness compared with our previous formulation of 17% P407 (96 kPa versus 10 kPa). These characteristics were optimal for microsurgical intravascular use, offering surgical precision and control between liquid and solid states, depending on the surgically controlled local temperature. CONCLUSIONS: Use of 45% P188 without bovine serum albumin demonstrated optimal rheologic and translational properties as a microvascular stent for sutureless anastomosis. Rapid transition, increased stiffness, and safety profile demonstrate safe translational application for human clinical trials. PMID- 26818290 TI - Management of Stenosing Flexor Tenosynovitis: Maximizing Nonoperative Success without Increasing Morbidity. AB - BACKGROUND: Traditional nonoperative management of stenosing tenosynovitis is limited to one corticosteroid injection, followed by surgery in the case of failure. Recently, nonoperative strategies have been extended to include two or three injections despite the absence of large prospective studies supporting this practice. METHODS: A prospective study was performed of all patients presenting with stenosing tenosynovitis to a single surgeon (R.S.R.) over a 22-year period. Patients with potentially confounding comorbidities were excluded. All digits received one to three injections of triamcinolone acetonide plus local anesthetic into the tendon sheath. Data were analyzed by digit. RESULTS: Five hundred seventy-one digits (401 patients) were included. Digits that were symptomatic for 3 months or less were more likely to resolve after one injection than those that were symptomatic for more than 3 months (OR, 2.6; 95 percent CI, 1.67 to 4.0; p < 0.01). For the digits that failed to resolve after the first injection, those that were symptomatic for 5 months or less before one injection were more likely to respond to a second injection than those that were symptomatic for more than 5 months (OR, 9.4; 95 percent CI, 3.0 to 29.7; p < 0.01). Eight digits received three injections, after which six (75 percent) achieved remission. There were no instances of tendon/pulley rupture, infection, or soft-tissue atrophy. CONCLUSIONS: Stenosing tenosynovitis is more likely to respond to nonoperative therapy when treated before 3 months. It is safe and effective to administer more than one corticosteroid injection, as second and third doses increase the overall remission rate without increasing morbidity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 26818291 TI - Office-Based Post-Axial Polydactyly Excision in Neonates, Infants, and Children. AB - BACKGROUND: In adult hand surgery literature, there are multiple publications highlighting the successful use of office-based hand surgery in the treatment of hand conditions. There are few instances of office-based hand surgery in the pediatric population present in the literature. Polydactyly of the hand is one of the most common congenital hand malformations. The authors present a case series of successfully performed in-office surgical excision of the type B postaxial polydactylous digit in infants and children. The added health care utilization improvements by performing this in the office, as well as lack of exposure to general anesthesia are reviewed. METHODS: A retrospective review of the patients treated was completed and the technique of in-office excision documented. RESULTS: Over a 15 month period, a total of twenty-six children were treated in the office for postaxial polydactyly. The average age of the child at the time of excision was 3.3 months old, with a median of 1.4 months with a range of 9 days 4.2 years. There were no postprocedure complications in function or sensation. CONCLUSIONS: The authors report a case series of successful surgical excision of type B postaxial polydactyly in newborns, infants, and children in an office setting with the use of lidocaine with epinephrine. This technique is a cost conscious approach to the condition without the need for general anesthesia. This demonstrates excellent results with improved safety without sacrificing quality. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 26818292 TI - Utility of Tongue Stitch and Nasal Trumpet in the Immediate Postoperative Outcome of Cleft Palatoplasty. AB - BACKGROUND: Postoperative airway obstruction is a feared complication following cleft palate repair. The aim of this study was to evaluate the effectiveness of tongue stitches and nasal trumpets that have been used in an attempt to prevent this complication. METHODS: An 8-year (2005 to 2013) retrospective review of palatoplasties performed at a tertiary care center was conducted. Patients were divided into three groups: those with no airway protective measure, those with a tongue stitch only, and a group with nasal trumpet and tongue stitch. Recorded variables included sex, age, Veau classification, and comorbidities. Primary outcomes measured were postoperative respiratory distress, readmission, and reoperation rates. RESULTS: Fifty-eight patients underwent palatoplasties with no airway protective measure, 252 patients had tongue stitch only, and 87 had tongue stitch and nasal trumpet. There were no significant differences between groups with respect to comorbidities except that cleft lip was more prevalent in the no airway protection group than in the other two groups (p = 0.04). There was no significant difference in the incidence of reintubation, intensive care unit transfer, surgery-related readmissions, or reoperation. Respiratory complications were significantly increased in the nasal trumpet group even after adjusting for age and weight. Length of stay was also significantly (p < 0.01) shortened when comparing no airway protection to those who underwent both nasal trumpet and tongue suture placement. CONCLUSIONS: The use of a tongue stitch, with or without nasal trumpet, did not correlate with improved safety and outcomes. Patients without these airway protective measures had a shorter hospital stay. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 26818293 TI - Antibiotic Use in Primary Palatoplasty: A Survey of Practice Patterns, Assessment of Efficacy, and Proposed Guidelines for Use. AB - BACKGROUND: The literature provides no guidelines for antibiotic use in palatoplasty. The authors sought to ascertain practice patterns; review a large, single-surgeon experience, and propose guidelines for antibiotic use in primary palatoplasty. METHODS: A six-question survey was e-mailed to all surgeons of the American Cleft Palate-Craniofacial Association. A retrospective study was also conducted of the senior author's 10-year primary palatoplasty series, and two groups were studied. Group 1 received no antibiotics. Group 2 received preoperative and/or postoperative antibiotics. RESULTS: Three hundred twelve of 1115 surgeons (28 percent) responded to the survey. Eighty-five percent administered prophylactic antibiotics, including 26 percent who used a single preoperative dose. A further 23 percent gave 24 hours of postoperative therapy; 12 percent used 25 to 72 hours, 16 percent used 4 to 5 days, and 12 percent used 6 to 10 days. Five percent of surgeons administered penicillin, 64 percent administered a first-generation cephalosporin, 13 percent administered ampicillin/sulbactam, and 8 percent gave clindamycin. The authors reviewed 311 patients; 173 receive antibiotics and 138 did not. Delayed healing and fistula rates did not differ between groups: 16.8 percent versus 15.2 percent (p = 0.71) and 2.9 percent versus 1.4 percent (p = 0.47), respectively. A single patient treated without antibiotics developed a postoperative bacteremia. This case did not meet the Centers for Disease Control definition of a surgical site infection, but the patient developed a palatal fistula. CONCLUSIONS: Antibiotic use in primary palatoplasty varies widely. The authors' data support a clinician's choice to forego antibiotic use; however, given the significance of palatal fistulae and the single case of postoperative streptococcal bacteremia, the study group recommends a single preoperative dose of ampicillin/sulbactam. Current evidence cannot justify the use of protracted antibiotic regimens. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 26818294 TI - Discussion: Antibiotic Use in Primary Palatoplasty: A Survey of Practice Patterns, Assessment of Efficacy, and Proposed Guidelines for Use. PMID- 26818295 TI - Facial Fractures in the Aging Population. AB - BACKGROUND: As the U.S. population ages and life expectancy increases, the number of elderly patients seeking trauma care and treatment for facial fractures will increase. Understanding age-related differences in the pattern, cause, and management of these fractures is essential for improving care. METHODS: A retrospective review of adults presenting to a Level I trauma center was performed to evaluate age-related differences in facial fractures. Descriptive statistics were used to compare fracture number, type, cause of injury, management, and adverse events between elderly (older than 64 years) and younger cohorts (aged 18 to 64 years). Logistic regression was used to evaluate the effect of age on fracture type while controlling for potential confounding variables. RESULTS: Two thousand twenty-three adult patients sustained a facial fracture from 2001 to 2011. Two hundred nine patients were elderly and 1814 were younger. Regarding cause of injury, older patients were more likely to fall and younger patients were more likely to be injured through assaults, motor vehicle collisions, or sports (p < 0.0001). Elderly patients sustained a higher incidence of maxillary (16.3 percent versus 11.4 percent; p = 0.0401), nasal (54.1 percent versus 45.3 percent; p = 0.0156), and orbital floor fractures (28.2 percent versus 18.1 percent; p = 0.004) and a lower incidence of mandible fractures (10.1 percent versus 21.3 percent; p = 0.0001). The elderly had significantly less operative intervention (24.9 percent versus 43 percent; p < 0.0001) and were less likely to experience complications (5.3 percent versus 10.5 percent; p = 0.0162). CONCLUSION: Elderly patients tend to suffer from less severe facial fractures, requiring less need for operative intervention, likely secondary to low-energy mechanisms of injury. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II. PMID- 26818296 TI - Anticoagulation for Hypercoagulable Patients Associated with Complications after Large Cranioplasty Reconstruction. AB - BACKGROUND: Despite advancements in materials and techniques used for cranial reconstruction, complication rates following reconstructive cranioplasty remain significant. METHODS: In this study, the authors assessed the association of perioperative anticoagulation use and/or a hypercoagulable state with minor (i.e., not requiring surgical intervention) and major (i.e., surgical intervention required) complications after reconstructive cranioplasty for large skull defects. A retrospective cohort review of 108 consecutive cranioplasties performed between 2011 and 2014 was conducted. A multiple logistic regression analysis was performed to identify the adjusted association between the predictor variables and complications. RESULTS: Twenty-three primary (21.3 percent) and 85 secondary (78.7 percent) cranioplasties were performed on 94 patients with a median age of 50 years (interquartile range, 38 to 63 years). Median full thickness calvarial defect size was 154 cm (interquartile range, 104 to 230 cm). Eleven minor (10.2 percent) and 18 major postoperative complications (16.7 percent) occurred in 26 cases (24.1 percent). Multiple logistic regression analysis revealed that coagulation status (i.e., perioperative use of anticoagulation therapy or hypercoagulable state) was statistically significant in predicting minor complications (OR, 7.8; 95 percent CI, 2.4 to 25.2; p = 0.001). Of note, the odds of a minor complication were an order of magnitude higher when both perioperative anticoagulation and a hypercoagulable state were present. CONCLUSION: To the authors' knowledge, this is the first study to document that the use of perioperative anticoagulant therapy for patients with thromboembolic conditions is a positive predictor of complications following cranioplasty reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 26818297 TI - Continuous Positive Airway Pressure for Upper Airway Obstruction in Infants with Pierre Robin Sequence. AB - The aim of the study was to evaluate noninvasive continuous positive airway pressure as first-line treatment for upper airway obstruction in neonates with Pierre Robin sequence. Forty-four neonates were enrolled and classified in 4 groups: ventilator-dependent patients (severe upper airway obstruction group), patients with clinical upper airway obstruction, an abnormal (moderate upper airway obstruction group) or normal polygraphy (mild upper airway obstruction group), and those with no clinical upper airway obstruction (no upper airway obstruction group). Five neonates in the severe upper airway obstruction group (n = 9) were successfully managed by noninvasive continuous positive airway pressure and 4 required a tracheotomy. The moderate upper airway obstruction group (n = 4) was successfully managed by noninvasive continuous positive airway pressure and the other patients by prone positioning. Continuous positive airway pressure represents an effective treatment of upper airway obstruction in Pierre Robin sequence and may be recommended in selected patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 26818298 TI - Surgeon Reimbursements in Maxillofacial Trauma Surgery: Effect of the Affordable Care Act in Ohio. AB - BACKGROUND: Surgical treatment of maxillofacial injuries has historically been associated with low reimbursements, mainly because of the high proportion of uninsured patients. The Affordable Care Act, implemented in January of 2014, aimed to reduce the number of uninsured. If the Affordable Care Act achieves this goal, surgeons may benefit from improved reimbursement rates. The authors' purpose was to evaluate the effects of the Affordable Care Act on payor distribution and surgeon reimbursements for maxillofacial trauma surgery at their institution. METHODS: A review of all patients undergoing surgery for maxillofacial trauma between January of 2012 and December of 2014 was conducted. Insurance status, and amounts billed and collected by the surgeon, were recorded. Patients treated before implementation of the Affordable Care Act were compared to those treated after. RESULTS: Five hundred twenty-three patients were analyzed. Three hundred thirty-four underwent surgery before implementation of the Affordable Care Act, and 189 patients underwent surgery after. After implementation of the Affordable Care Act, the proportion of uninsured decreased (27.2 percent to 11.1 percent; p < 0.001) and the proportion of patients on Medicaid increased (7.8 percent to 25.4 percent; p < 0.001). Overall surgeon reimbursement rate increased from 14.3 percent to 19.8 percent (p < 0.001). CONCLUSIONS: After implementation of the Affordable Care Act, we observed a significant reduction in the proportion of maxillofacial trauma patients who were uninsured. Surgeons' overall reimbursement rate increased. These trends should be followed over a longer term to determine the full effect of the Affordable Care Act. PMID- 26818299 TI - Long-Term Operative Outcomes of Preoperative Computed Tomography-Guided Virtual Surgical Planning for Osteocutaneous Free Flap Mandible Reconstruction. AB - BACKGROUND: Osteocutaneous free flaps have become the primary reconstructive modality for segmental mandibulectomy defects. The advent of preoperative virtual surgical planning with stereolithic models and cutting templates has led to significant refinements in operative technique. In this article, the authors examine the value of computed tomography-guided preoperative virtual surgical planning on operative outcomes and efficiency after mandibular reconstruction with osteocutaneous free flaps. METHODS: A retrospective review was performed of all patients undergoing free flap mandible reconstruction at a single cancer center from 2002 to 2013. Surgical technique and operative time were assessed, as were overall complications and outcomes. Postoperative computed tomographic scans were also examined to determine the accuracy of osteotomies with and without virtual surgical planning. RESULTS: Ninety-two patients underwent osteocutaneous free flap reconstruction of the mandible during the study period. In 43 patients, the shaping of the neomandible was performed based on the prefabricated stereolithic models. The remaining 49 patients underwent preoperative computed tomographic imaging to design patient-specific cutting guides for the native mandible and the osteocutaneous flap. The use of preoperative computed tomography guided planning resulted in less burring, fewer osteotomy revisions, and less bone grafting. Virtual surgical planning also significantly decreased operative time (666 minutes versus 545 minutes; p < 0.005). Review of postoperative computed tomographic scans demonstrated decreased rates of bony nonunion with virtual surgical planning, and there were no significant differences in overall outcomes or complications between the groups. CONCLUSIONS: Preoperative virtual surgical planning has refined mandible reconstruction with osteocutaneous free flaps through the introduction of patient-specific models, prebent plates, and osteotomy guides. Virtual surgical planning decreases operative time and improves the accuracy of free flap mandibular reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 26818300 TI - Discussion: Long-Term Operative Outcomes of Preoperative Computed Tomography Guided Virtual Surgical Planning for Osteocutaneous Free Flap Mandible Reconstruction. PMID- 26818301 TI - The Folded Ulnar Forearm Flap for Nasal Reconstruction. AB - BACKGROUND: Many strategies exist to reconstruct composite nasal defects, but free flaps are necessary for extensive defects. The workhorse radial forearm flap is hair-bearing and donor-site cosmesis is unfavorable. The ulnar forearm flap is overlooked despite important aesthetic benefits. The authors describe their experience with the ulnar forearm flap, with a novel folding technique in staged nasal reconstruction. METHODS: Between December of 2010 and April of 2015, 10 nasal reconstructions in five men and five women were performed. Average patient age was 47.6 years (range, 31 to 76 years). The ulnar forearm flap was designed as a narrow contiguous flap along the ulnar vascular axis. Inset began with the nasal floor; the flap was then tubularized twice to create nasal passages before it was folded on itself for coverage. Caudal edges were sewn together to create alae and a columella. Follow-up time, complications, number of operations, and reconstructive duration were documented. RESULTS: Average follow-up was 25.2 months (range, 18 to 44 months). Patients had satisfactory aesthetic and functional outcomes after 6.4 operations (range, five to eight) over 11.1 months (range, 8 to 18 months). Partial necrosis of the alar lining in one case was salvaged with the covering flap. Two cases of chondritis were managed with conservative debridement and antibiotics. One case of severe chondritis necessitated removal and de novo reconstruction. CONCLUSIONS: The ulnar forearm flap is safe and reliable in nasal reconstruction, with superior donor-site cosmesis. The tubular folding method creates a vascular envelope amenable to same stage framework construction. With thoughtful planning and sufficient refinement, excellent aesthetic and functional results are achievable. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID- 26818302 TI - Posterior Component Separation with Transversus Abdominis Release: Technique, Utility, and Outcomes in Complex Abdominal Wall Reconstruction. AB - BACKGROUND: Ventral hernia formation is a frequent and increasingly difficult problem. Nonmidline hernias, parastomal hernias, hernias near bony landmarks, and recurrent ventral hernias (especially after anterior component separation) present particular challenges. Typical reconstructive techniques may struggle to reestablish abdominal domain and to create a lasting repair. Posterior component separation with transversus abdominis release is a novel technique that offers a durable solution to a variety of complex ventral hernias. METHODS: The posterior rectus sheath is incised and the retrorectus plane is developed. In a modification of the Rives-Stoppa technique, the transversus abdominis is released medial to the linea semilunaris to expose a broad plane that extends from the central tendon of the diaphragm superiorly, to the space of Retzius inferiorly, and laterally to the retroperitoneum. This preserves the neurovascular bundles innervating the medial abdominal wall. Mesh is placed in a sublay fashion above the posterior layer. In an overwhelming majority of patients, the linea alba is reconstructed, creating a functional abdominal wall with wide mesh reinforcement. RESULTS: The technique is reliable and durable, with a 5 percent recurrence rate at 2 years. Although wound complications occur with a frequency similar to that of other techniques, they tend to be less severe, rarely requiring operative debridement. The technique is applicable to a broad range of hernias, including midline, parastomal, flank, subcostal, and recurrent hernias after prior component separations. CONCLUSION: Posterior component separation with transversus abdominis release is a versatile, easy-to-learn technique of hernia repair that offers a reliable, durable solution to complex abdominal wall reconstruction. PMID- 26818303 TI - A Cost-Utility Assessment of Mesh Selection in Clean-Contaminated Ventral Hernia Repair. AB - BACKGROUND: Mesh reinforcement can reduce hernia recurrence, but mesh selection is poorly understood, particularly in contaminated defects. Acellular dermal matrix has enabled single-stage ventral hernia repair in clean-contaminated wounds but can be associated with higher complications and cost compared with synthetic mesh. This study evaluated the cost-utility of synthetic mesh and acellular dermal matrix for clean-contaminated ventral hernia repairs. METHODS: A systematic review of articles comparing outcomes for synthetic and acellular dermal matrix repairs identified 14 ventral hernia repair-specific health states. Quality-adjusted life years were determined through Web-based visual analog scale survey of 300 nationally representative individuals. Overall expected cost and quality-adjusted life-years for ventral hernia repair were assessed using a Monte Carlo simulation with sensitivity analyses. RESULTS: Synthetic mesh reinforcement had an expected cost of $15,776 and quality-adjusted life-year value gained of 21.03. Biological mesh had an expected cost of $23,844 and quality-adjusted life year value gained of 20.94. When referencing a common baseline (do nothing), acellular dermal matrix (incremental cost-effectiveness ratio, 3378 ($/quality adjusted life years)) and synthetic mesh (incremental cost-effectiveness ratio, 2208 ($/quality-adjusted life years)) were judged cost-effective, although synthetic mesh was more strongly favored. Monte Carlo sensitivity analysis demonstrated that synthetic mesh was the preferred and most cost-effective strategy in 94 percent of simulations, supporting its overall greater cost utility. Despite varying the willingness-to-pay threshold from $0 to $100,000 per quality-adjusted life-year, synthetic mesh remained the optimal strategy across all thresholds in sensitivity analysis. CONCLUSION: This cost-utility analysis suggests that synthetic mesh repair of clean-contaminated hernia defects is more cost-effective than acellular dermal matrix. PMID- 26818304 TI - Discussion: A Cost-Utility Assessment of Mesh Selection in Clean-Contaminated Ventral Hernia Repair. PMID- 26818305 TI - Expanding the Applications of the Profunda Artery Perforator Flap. AB - BACKGROUND: The profunda artery perforator free flap has not gained traction for nonbreast reconstruction, likely because of the presence of a proven workhorse in the anterolateral thigh flap. The authors believe that the profunda artery perforator flap offers similar coverage characteristics with the benefits of a medial donor site, a more consistent anatomy, and relatively easy dissection. The authors review their indications, technique, and outcomes in seven patients requiring eight free flap reconstructions. METHODS: The authors applied the use of the vertically oriented profunda artery perforator flap to both lower extremity and head and neck reconstructions in which an anterolateral thigh flap would normally have been used. Details reviewed include soft-tissue defect, perforator location, flap size, recipient vessel, and complications. RESULTS: Eight soft-tissue defects were covered with a vertically oriented profunda artery perforator flap in seven patients. Six reconstructions were for distal lower extremity and two were for head and neck reconstruction, both trauma and oncologic reconstructions. Flap sizes ranged from 40 to 92 cm. The pedicle length ranged from 7 to 10 cm. There were no partial or complete flap losses. One complication of seroma at the donor site requiring washout and closure was encountered. CONCLUSIONS: The profunda artery perforator flap is a safe and effective option for perforator-based free flap reconstruction with relative ease of harvest and an inconspicuous donor site. This flap offers an excellent alternative to the anterolateral thigh flap. In certain patient demographics, the profunda artery perforator flap should be considered as a primary option. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID- 26818306 TI - Comprehensive Observations of Resident Evolution: A Novel Method for Assessing Procedure-Based Residency Training. AB - BACKGROUND: Assessment of surgical skills in the operating room remains a challenge. Increasing documentation requirements of the Accreditation Council for Graduate Medical Education are necessitating mechanisms to document trainee competence without hindering operative turnover. The authors created a comprehensive electronic resource to facilitate plastic surgery training program compliance with changes mandated by Next Accreditation System Milestones and the ACGME. METHODS: In 2013, the authors implemented the Comprehensive Observations of Resident Evolution, or CORE, a Web-based tool to assess plastic surgery residents. It comprises a rapid electronic assessment of resident operating room performance completed after each surgery; a data dashboard displaying graphical summaries of resident progress by case, Milestone, or current procedural terminology code; and an electronic Milestones tracker (MileMarker), which enables ongoing trainee assessments. RESULTS: From January through October of 2014, 24 residents completed nearly 1300 Operative Entrustability Assessments. Thirty-eight percent of residents reported more immediate feedback regarding operative performance. The assessment demonstrates construct validity, which distinguishes novice residents from experienced residents. Individual case data identify resident-specific operative strengths and weaknesses. Using assessment data, the first two Clinical Competency Committee reviews were 81 percent and 87 percent shorter than Milestones pilot test site reports (average, 11.5 and 8 minutes versus 60 minutes per resident, respectively). CONCLUSIONS: Comprehensive Observations of Resident Evolution is capable of capturing operative performance data on all operating room cases by primary current procedural terminology code. It increases immediate attending/trainee feedback and assessment transparency, enables trainee self-monitoring, and informs end-of-rotation reviews, programwide assessments, and tailoring of training to address specific needs. It is a valuable resource for tracking resident progress in real-time while maintaining compliance with evolving ACGME requirements. PMID- 26818307 TI - So You Have a Research Idea: A Survey of Databases Available for Plastic Surgery Research. AB - Plastic surgery research using large databases has increased dramatically over the past 20 years. With the magnitude and breadth of information available in these databases, researchers are able to more easily answer a wide variety of research questions. This study sought to provide a comprehensive comparative analysis of the relevant databases for plastic surgery research. Database information, data collection methods, acquisition details, and variable availability were collected for 19 large databases. Examples of potential future research utility were ascribed to each database based on this comprehensive analysis. With a greater understanding of the content, strengths, and limitations of these databases, researchers will be better equipped to select the most appropriate database to answer a specific research question. PMID- 26818308 TI - The Impact of National Institutes of Health Funding on Scholarly Productivity in Academic Plastic Surgery. AB - BACKGROUND: The h-index is an objective measure of an investigator's scholarly impact. The purpose of this investigation was to determine the association between scholarly impact, as measured by the h-index, and the procurement of National Institutes of Health (NIH) grant funding among academic plastic surgeons. METHODS: This was a case-control study of NIH-funded plastic surgery faculty identified on the RePORTER database. Non-NIH-funded faculty from the top 10 NIH-funded programs served as a control group. The mean h-index was calculated from Scopus (Elsevier, London, United Kingdom) and compared by funding status, academic rank, and terminal degree(s). The relationship between h-index and career NIH funding was elucidated via Spearman's correlation coefficient. RESULTS: NIH-funded faculty had higher h-indices than nonNIH-funded faculty (23.9 versus 9.9, p < 0.001), an effect that persisted when controlling for academic rank. Higher rank correlated with higher h-indices and predicted greater NIH funding (p < 0.05). The h-index did not vary by terminal degree (p > 0.05), but investigators with a master's degree exhibited a trend toward greater NIH funding. Higher h-indices correlated with greater NIH funding (r = 0.481, p < 0.001). CONCLUSIONS: A strong relationship exists between scholarly impact and the procurement of NIH funding. Faculty with greater funding had greater scholarly impact, as measured by the h-index, which suggests that this tool may have utility during the NIH grant application process. PMID- 26818309 TI - A Systematic Review of Surgical Randomized Controlled Trials: Part I. Risk of Bias and Outcomes: Common Pitfalls Plastic Surgeons Can Overcome. AB - BACKGROUND: The authors investigated the methodological validity of plastic surgery randomized controlled trials that compared surgical interventions. METHODS: An electronic search identified randomized controlled trials published between 2000 and 2013. Reviewers, independently and in duplicate, assessed manuscripts and performed data extraction. Methodological safeguards (randomization, allocation concealment, blinding, and incomplete outcome data) were examined using the Cochrane risk of bias tool. Regression analysis was used to identify trial characteristics associated with risk of bias. RESULTS: Of 1664 potentially eligible studies, 173 randomized controlled trials were included. Proper randomization and allocation concealment methods were described in 61 of 173 (35 percent) and 21 of 173 (12 percent), respectively. Outcome assessors were blinded in 58 of 173 (34 percent) trials, and patients were blinded in 45 of 173 (26 percent). Follow-up rates were high, with 99 of 173 (57 percent) randomized controlled trials appearing to have complete follow-up. An intention-to-treat analysis was used in 19 of 173 (11 percent) trials. One-third (58 of 173, 34 percent) did not state their primary outcomes. The most common type of primary outcome used was a symptom/quality of life, class III, outcome (73 of 173, 42 percent). Multinomial regression demonstrated trials reporting an a priori sample size as more likely to have a low risk of bias (p = 0.001). CONCLUSIONS: This article highlights methodological safeguards that plastic surgeons should consider when interpreting results of a surgical randomized controlled trial. Allocation concealment, outcome assessor blinding, and patient blinding were identified as areas of concern. Valid and reliable outcome measures are being used in plastic surgery. This analysis provides strong rationale for continued focus on the performance and reporting of clinical trials within our specialty. PMID- 26818310 TI - Discussion: A Systematic Review of Surgical Randomized Controlled Trials: Part I. Risk of Bias and Outcomes: Common Pitfalls Plastic Surgeons Can Overcome. PMID- 26818311 TI - Benefits and Risks of Prophylaxis for Deep Venous Thrombosis and Pulmonary Embolus in Plastic Surgery: A Systematic Review and Meta-Analysis of Controlled Trials and Consensus Conference. AB - The goal of this consensus conference, sponsored by the American Association of Plastic Surgeons, was to perform a systematic review and meta-analysis of controlled trials to examine both the benefits and risks of venous thromboembolism prophylaxis in plastic surgery patients. The panel sought to assess the safety and effectiveness of recognized venous thromboembolism prophylaxis strategies, including variation in anesthetic management, use of elastic compression stockings or intermittent pneumatic compression, and use of chemoprophylaxis. The authors also sought to examine effectiveness and safety of prophylaxis in patients risk-stratified by procedure type or 2005 Caprini score. The panel met face to face in March of 2015 to perform an exhaustive review of the existing literature. The panel subsequently created consensus recommendations using the GRADE criteria. Important directions for future research were also identified. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID- 26818312 TI - The Role of Intraoperative Perfusion Assessment: What Is the Current State and How Can I Use It in My Practice? AB - Evolving intraoperative technology has an increased presence and usefulness in aiding surgeon clinical judgment. Many surgical devices are readily available as an adjunct to this gold standard assessment of adequate tissue perfusion. Intraoperative perfusion monitoring provides surgeons with the ability to interpret additional information that enhances surgical decision-making in real time. Technologies include various dye-based and non-dye-based near-infrared angiography, tissue oximetry measurements, and ultrasound-based tools. This review summarizes the available intraoperative technologies for planning and assessment of tissue perfusion in plastic and reconstructive surgery. The authors discuss the available literature for the individual devices and supporting evidence for their use. The authors recommend the evidence-based use of these tools in indicated surgical cases to improve clinical outcomes. PMID- 26818313 TI - Technology and Plastic Surgery: Foreword. PMID- 26818316 TI - Using the Retrograde Internal Mammary System for Stacked Perforator Flap Breast Reconstruction: 71 Breast Reconstructions in 53 Consecutive Patients. AB - BACKGROUND: Abdominal tissue is the preferred donor source for autologous breast reconstruction, but in select patients with inadequate tissue, additional volume must be recruited to achieve optimal outcomes. Stacked flaps are an effective approach in these cases, but can be limited by the need for adequate recipient vessels. This article reports outcomes for the use of the retrograde internal mammary system for stacked flap breast reconstruction in a large number of consecutive patients. METHODS: Fifty-three patients underwent stacked autologous tissue breast reconstruction with a total of 142 free flaps. Thirty patients underwent unilateral stacked deep inferior epigastric perforator (DIEP) flap reconstruction, five had unilateral stacked profunda artery perforator flap reconstruction, one had bilateral stacked DIEP/superior gluteal artery perforator flap reconstruction, and 17 underwent bilateral stacked DIEP/profunda artery perforator flap reconstruction. In all cases, the antegrade and retrograde internal mammary vessels were used for anastomoses. In situ manometry studies were also conducted comparing the retrograde internal mammary arteries in 10 patients to the corresponding systemic pressures. RESULTS: There were three total flap losses (97.9 percent flap survival rate), two partial flap losses, four reexplorations for venous congestion, and three patients with operable fat necrosis. The mean weight of the stacked flaps for each reconstructed breast was 622.8 g. The retrograde internal mammary mean arterial pressures were on average 76.6 percent of the systemic mean arterial pressures. CONCLUSIONS: The results demonstrate that the retrograde internal mammary system is capable of independently supporting free tissue transfer. These vessels provide for convenient dissection and improved efficiency of these cases, with successful postsurgical outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 26818317 TI - Evaluation of Aesthetic and Quality-of-Life Results after Immediate Breast Reconstruction with Definitive Form-Stable Anatomical Implants. AB - BACKGROUND: Although there are many reports on different techniques in breast reconstruction, there are few data regarding immediate breast reconstruction with definitive form-stable anatomical implants in terms of aesthetics and quality-of life outcomes. METHODS: Ninety-four patients underwent mastectomy with immediate breast reconstruction using anatomical implants and contralateral symmetrization. Aesthetic results were evaluated by three different methods: the patient's self report, the assessment of four independent specialists (two breast surgeons and two plastic surgeons from different institutions), and the BCCT.core software. Quality of life was evaluated by means of the BREAST-Q instrument. RESULTS: Average age +/- SD was 52.1 +/- 11.6 years. Most of patients had medium size breasts and T1 tumors. Patients had evaluated their aesthetic results better than did software and specialists. There was no significant difference in the comparison between software and specialist's evaluation. Multifactorial analysis showed that age older than 70 years and radiotherapy were significant risk factors for poor aesthetic outcomes after immediate breast reconstruction with implants. Considering quality of life, most of the patients were satisfied with their outcome and psychosocial and sexual well-being. CONCLUSION: Immediate breast reconstruction with implants and contralateral symmetrization had a positive impact on the quality of life and showed satisfactory outcomes when evaluated by subjective and objective methods. PMID- 26818318 TI - Readability Assessment of Patient Information about Lymphedema and Its Treatment. AB - BACKGROUND: Patient use of online resources for health information is increasing, and access to appropriately written information has been associated with improved patient satisfaction and overall outcomes. The American Medical Association and the National Institutes of Health recommend that patient materials be written at a sixth-grade reading level. In this study, the authors simulated a patient search of online educational content for lymphedema and evaluated readability. METHODS: An online search for the term "lymphedema" was performed, and the first 12 hits were identified. User and location filters were disabled and sponsored results were excluded. Patient information from each site was downloaded and formatted into plain text. Readability was assessed using established tests: Coleman-Liau, Flesch-Kincaid, Flesch Reading Ease Index, FORCAST Readability Formula, Fry Graph, Gunning Fog Index, New Dale-Chall Formula, New Fog Count, Raygor Readability Estimate, and Simple Measure of Gobbledygook Readability Formula. RESULTS: There were 152 patient articles downloaded; the overall mean reading level was 12.6. Individual website reading levels ranged from 9.4 (cancer.org) to 16.7 (wikipedia.org). There were 36 articles dedicated to conservative treatments for lymphedema; surgical treatment was mentioned in nine articles across four sites. The average reading level for conservative management was 12.7, compared with 15.6 for surgery (p < 0.001). CONCLUSIONS: Patient information found through an Internet search for lymphedema is too difficult for many American adults to read. Websites queried had a range of readability, and surgeons should direct patients to sites appropriate for their level. There is limited information about surgical treatment available on the most popular sites; this information is significantly harder to read than sections on conservative measures. PMID- 26818319 TI - Maximizing Symmetry in Upper Blepharoplasty: The Role of Microptosis Surgery. AB - BACKGROUND: Traditional descriptions of blepharoplasty and ptosis surgery focus on the incision and eyelid crease. However, it may be more useful to consider the tarsal platform show as the important construct in analyzing and planning aesthetic eyelid surgery. METHODS: In order to measure and characterize the key contours of the eyelid, the authors find it helpful to consider the brow fat span, tarsal platform show, and margin reflex distance. RESULTS: Subtle eyelid ptosis can result in asymmetry by lengthening the tarsal platform show, and it is exacerbated by the tendency for the eyebrow to compensate. When ptosis is asymmetric, the plan should usually include asymmetric ptosis surgery. There are two general patterns that can be recognized and used for planning to address preoperative tarsal platform show asymmetry. If the tarsal platform show is longer on the side with worse blepharoptosis, then asymmetric or unilateral ptosis surgery will improve symmetry. In the cases of symmetric show despite asymmetric blepharoptosis, there may be bony and soft-tissue asymmetry, which leads to crowding of the orbit on the more ptotic side. Surgical planning should include consideration to increase the tarsal platform show on the more crowded side. It is not necessary to cut the eyelid skin in order to alter the tarsal show and brow fat span; ptosis surgery alone, by altering the eyelid position and eyebrow compensation, can reset the tarsal platform show/brow fat span relationship. CONCLUSIONS: It is important to recognize preoperative asymmetry, to predict the resetting of compensatory mechanisms, and to design asymmetric surgery, in order to maximize postoperative symmetry. PMID- 26818320 TI - Does the Eyebrow Sag with Aging? An Anthopometric Study of 95 Caucasians from 20 to 79 Years of Age. AB - BACKGROUND: It is commonly assumed that a progressive sagging of the eyebrow occurs with the facial aging process. Only a few studies have analyzed this modification, and the findings are disparate and inconclusive. This study, based on reproducible and validated data, aimed to quantify the modifications of eyebrow position that may occur with aging. Also analyzed were the effects of these eyebrow position changes on the upper eyelid and on frontal muscle activity. METHODS: The study included 95 Caucasian adults divided in three groups: 20 to 39, 40 to 59, and 60 to 79 years of age. Photographic portraits were made using a standardized photograph protocol. Eyebrow position was evaluated from the intercanthal line to four points along the upper margin of the eyebrow. The upper eyelid height, the lid sulcus height, and the upper iris coverage were measured. Severity of the forehead lines was analyzed using a validated scale. Reliability and validity of all measures were controlled beforehand. RESULTS: No significant differences were found when comparing eyebrow height above the medial canthus, the pupil, the lateral sclero-corneal limbus, and the lateral canthus between groups (p > 0.5). In addition, results suggested an increase of dermatochalasis when eyebrow height decreased. Also demonstrated was a significant increase of frontal muscle activity with aging. CONCLUSIONS: In contrast to conventional descriptions, this study demonstrated the stability of the eyebrow position with aging. This results from a physiological state of muscular compensation and may help explain the questionable results of eyebrow surgery. PMID- 26818321 TI - Bergamo 3D Rhinoplasty Software: Select, Store, and Share Surgical Maneuvers in a Three-Dimensional Nasal Model. AB - BACKGROUND: Rhinoplasty is considered the most challenging chapter of plastic surgery due to its variability and the continuing evolution of surgical maneuvers. Worksheets became essential to unequivocally record surgical steps and to demonstrate their reciprocal effects/interactions during the follow-up period. After 1989, no other software was created to upgrade the Gunter Rhinoplasty Diagrams, the forefather and benchmark of the rhinoplasty "virtual" worksheet maker. METHODS: The authors built a new standard three-dimensional nasal framework model in STL format. All the basic components were modified to simulate the interaction among sutures, grafts, and the most common maneuvers performed during rhinoplasty. The authors created a total of 669 (99 built-in units and 285 unilateral units) three-dimensional figures which can be selected by the surgeon from among 230 options. The interface for the surgeon is Bergamo 3D Rhinoplasty Software. RESULTS: Bergamo 3D Rhinoplasty Software is made up of the database section, which gathers all the patient's personal information and documents, and the surgery section, which groups multiple selection lists in 10 surgical areas. Eighty percent of the options modify the original shape of the three-dimensional model. Several options help the surgeon to tailor the final result and to export it both in desktop software and in a real three-dimensional printed model. CONCLUSIONS: Bergamo Rhinoplasty Software revolutionizes the concept of patient and surgical data storage. Furthermore, the immediacy of three dimensions facilitates communication with patients, allows case sharing with colleagues, simplifies teaching, and encourages the surgeon's self-analysis and professional growth. Customization of the original model and of the maneuvers is the main limitation of the software, because of the currently existing technology in 2014. PMID- 26818322 TI - Adipose-Derived Stem Cells Promote Peripheral Nerve Regeneration In Vivo without Differentiation into Schwann-Like Lineage. AB - BACKGROUND: During recent decades, multipotent stem cells were found to reside in the adipose tissue, and these adipose-derived stem cells were shown to play beneficial roles, like those of Schwann cells, in peripheral nerve regeneration. However, it has not been well established whether adipose-derived stem cells offer beneficial effects to peripheral nerve injuries in vivo as Schwann cells do. Furthermore, the in situ survival and differentiation of adipose-derived stem cells after transplantation at the injured peripheral nerve tissue remain to be fully elucidated. METHODS: Adipose-derived stem cells and Schwann cells were transplanted with gelatin hydrogel tubes at the artificially blunted sciatic nerve lesion in mice. Neuroregenerative abilities of them were comparably estimated. Cre-loxP-mediated fate tracking was performed to visualize survival in vivo of transplanted adipose-derived stem cells and to investigate whether they differentiated into Schwann linage cells at the peripheral nerve injury site. RESULTS: The transplantation of adipose-derived stem cells promoted regeneration of axons, formation of myelin, and restoration of denervation muscle atrophy to levels comparable to those achieved by Schwann cell transplantation. The adipose derived stem cells survived for at least 4 weeks after transplantation without differentiating into Schwann cells. CONCLUSIONS: Transplanted adipose-derived stem cells did not differentiate into Schwann cells but promoted peripheral nerve regeneration at the injured site. The neuroregenerative ability was comparable to that of Schwann cells. Adipose-derived stem cells at an undifferentiated stage may be used as an alternative cell source for autologous cell therapy for patients with peripheral nerve injury. PMID- 26818323 TI - Regulable Transgene Expression in Dorsal Root Ganglia of a Replication-Defective Herpes Simplex Virus Type 1 Vector by Means of Sciatic Nerve Injection. AB - BACKGROUND: Targeted and controllable gene delivery to neurons is essential to efforts to facilitate peripheral nerve regeneration. The authors investigated both the in vitro and in vivo expression profiles of a tetracycline-controlled, replication-defective, herpes simplex virus type 1-based vector. METHODS: Mouse primary dorsal root ganglia cells were infected with QR9TO-LacZ in the absence or presence of tetracycline. LacZ gene expression was examined. It was also injected into sciatic nerves in CD-1 mice fed with and without tetracycline. LacZ expression in the upstream dorsal root ganglia was examined. RESULTS: Following inoculation with QR9TO-LacZ, approximately 40 percent of the cultured primary dorsal root ganglia cells exhibited strong LacZ activity in the presence of tetracycline at 48 and 72 hours, whereas little was detected in those in the absence of tetracycline. Quantitative analysis revealed that the beta galactosidase activity within cells exposed to tetracycline increased 181-fold at 48 hours (p < 0.001) and 47-fold at 72 hours after infection (p < 0.05) compared with those without tetracycline. However, this LacZ transgene activity in the presence of tetracycline tapered off to less than sevenfold over baseline 168 hours after infection (p < 0.05). Furthermore, successful uptake of this replication-defective viral vector was evident in upstream dorsal root ganglia after sciatic nerve injection in mice. In addition, its expression profile was similar to that in vitro, as strong beta-galactosidase activity was evident only in mice fed with a doxycycline-containing diet, and it tapered off by 168 hours. CONCLUSION: The replication-defective herpes simplex virus type 1-based vector, which provides tightly regulated transgene expression in dorsal root ganglia by means of peripheral nerve injection, represents an appealing approach to improve peripheral nerve regeneration. PMID- 26818324 TI - The Effect of Normovolemic and Hypervolemic Hemodilution on a Perforator Flap with Twisted Pedicle Model: Experimental Study in Rats. AB - BACKGROUND: Several studies showed the detrimental effect of pedicle torsion on flap survival; however, the impact of hemodilution in this peculiar condition has never been investigated. This study evaluated the effect of acute normovolemic and hypervolemic hemodilution on flap survival in a perforator flap with twisted pedicle model. METHODS: Sixty-three female Wistar rats were divided into three groups of 21 rats each: group 1, superficial inferior epigastric artery flap, which was elevated bilaterally and transposed back to the abdominal wall with different angles of rotation (i.e., 90, 180, 270, and 360 degrees); group 2, surgery with previous acute normovolemic hemodilution; and group 3, surgery with previous acute hypovolemic hemodilution. Normovolemic hemodilution was obtained, simultaneously removing 2 cc of blood and replacing it with an equal volume of isotonic sodium chloride 0.9% (two-thirds) plus hydroxyethyl starch 6% (one third). Hypervolemic hemodilution was obtained by hemodilution and a 20 percent blood volume expansion. Microangiography of the flap and histopathologic analyses were performed. RESULTS: Mean hematocrit values after hemodilution were 27.80 +/- 0.04 percent for the acute normovolemic hemodilution group and 27.01 +/- 0.03 percent for the acute hypovolemic hemodilution group. Twisting the pedicle at 90, 180, and 270 degrees had no effect on flap survival in all groups. However, 360 degree pedicle torsion showed flap edema, congestion, and necrosis. CONCLUSIONS: The authors' hemodilution protocol is an effective and reliable method that could be used to further investigate the impact of the hemodynamic changes that occur during hemodilution on flap microcirculation. The results obtained sustain the existence of a strong correlation between necrosis rate and hemodilution. PMID- 26818325 TI - An Examination of Differences in the New Bone Formation Promoted by Different Doses of Recombinant Human Parathyroid Hormone during Mandibular Distraction Osteogenesis. AB - BACKGROUND: The administration of different doses of parathyroid hormone to promote mandibular distraction osteogenesis remains unclear. The objective of the present study was to examine the effects of recombinant human parathyroid hormone on new bone formation during mandibular distraction osteogenesis and to investigate the dose-effect relationship associated with this phenomenon. METHODS: A total of 45 rabbits were used to establish the mandibular distraction osteogenesis model. The rabbits were divided into a control group (that received a subcutaneous injection of 1 ml of saline every other day) and experimental groups A, B, C, and D (that received subcutaneous injections of 10, 20, 30, and 40 MUg/kg of recombinant human parathyroid hormone, respectively, every other day). On days 1, 7, and 14 of the consolidation period after the distraction had been completed, new bone in the distraction region was examined through histomorphometric investigation and bone mineral density testing. RESULTS: On days 1, 7, and 14 of the fixation period, the number of osteoblasts, trabecular bone area, and bone mineral density were greater in each experimental group than in the control group. On day 1 of the consolidation period, group C featured the highest average number of osteoblasts. On day 14 of the consolidation period, group C exhibited the highest bone mineral densities and largest trabecular bone areas. CONCLUSIONS: Intermittent subcutaneous injections of recombinant human parathyroid hormone can promote new bone formation during mandibular distraction osteogenesis. Different doses of recombinant human parathyroid hormone promoted mandibular distraction osteogenesis to differing extents. PMID- 26818326 TI - The Use of Opioid Analgesics following Common Upper Extremity Surgical Procedures: A National, Population-Based Study. AB - BACKGROUND: The misuse of opioid analgesics is a major public health concern, and guidelines regarding postoperative opioid use are sparse. The authors examined the use of opioids following outpatient upper extremity procedures to discern the variation by procedure type and patient factors. METHODS: The authors studied opioid prescriptions among 296,452 adults older than 18 years who underwent carpal tunnel release, trigger finger release, cubital tunnel release, or thumb carpometacarpal arthroplasty from 2009 to 2013 using insurance claims drawn from the Truven Health MarketScan Commercial Claims and Encounters, which encompasses over 100 health plans in the United States. Using multivariable regression, the authors compared the receipt of opioids, number of days supplied, indicators of inappropriate prescriptions, and number of refills by patient factors. RESULTS: In this cohort, 59 percent filled a postoperative prescription for opioid medication, and 8.8 percent of patients had an indicator of inappropriate prescribing. The probability of filling an opioid prescription declined linearly with advancing age. On multivariate analysis, patients who had previously received opioids were more likely to fill a postoperative opioid prescription (66 percent versus 59 percent), receive longer prescriptions (24 versus 5 days), receive refills following surgery (24 percent versus 5 percent), and have at least one indicator of potentially inappropriate prescribing (19 percent versus 6 percent). CONCLUSIONS: Current opioid users are more likely to require postoperative opioid analgesics for routine procedures and more likely to receive inappropriate prescriptions. More evidence is needed to identify patients who derive the greatest benefit from opioids to curb opioid prescriptions when alternative analgesics may be equally effective and available. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III. PMID- 26818328 TI - Long-Term Results of Mandibular Distraction Osteogenesis with a Resorbable Device in Infants with Robin Sequence: Effects on Developing Molars and Mandibular Growth. AB - BACKGROUND: Mandibular distraction osteogenesis with a unidirectional resorbable device is an effective treatment option for severe upper airway obstruction in infants with Robin sequence. Long-term effects, especially with regard to tooth development and mandibular outgrowth, are not known. METHODS: Robin sequence infants with a follow-up of greater than or equal to 5 years were included. Baseline characteristics were extracted from medical records. Panoramic and lateral cephalometric radiographs were analyzed and patients were recalled for physical examination. RESULTS: Ten infants underwent mandibular distraction osteogenesis at a mean age of 3.7 months (median, 19 months; range, 11 days to 27 months). Mean length of follow-up was 6.8 years (range, 5.0 to 7.9 years). Ten Robin sequence infants without mandibular distraction osteogenesis (mean length of follow-up, 7.4 years; range, 6.7 to 8.9 years) were the controls. Shape anomalies, positional changes, and root malformations of molars were seen significantly more often than in the control group (p = 0.007, p = 0.009, and p = 0.043, respectively). Mandibular length was shorter (p = 0.030), but mandibular ramus height was comparable (p = 0.838) with that of the non-mandibular distraction osteogenesis group. Compared with healthy controls, all Robin sequence infants had a significantly shorter mandible. CONCLUSIONS: Mandibular distraction osteogenesis with a resorbable system reveals overall good short- and long-term results, but the effects on developing molars and mandibular outgrowth likely necessitate secondary procedures. This factor should be considered when deciding on treatment options and counseling of parents. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 26818327 TI - Long-Term Computed Tomographic Evaluation of Alveolar Bone Formation in Patients with Unilateral Cleft Lip and Palate after Early Secondary Gingivoalveoloplasty. AB - BACKGROUND: The goal of this study was to evaluate with a three-dimensional method the long-term quality of alveolar ossification in unilateral cleft lip and palate patients who underwent early secondary gingivoalveoloplasty according to the Milan surgical protocol. METHODS: The sample consisted of 63 computed tomographic scans of unilateral cleft lip and palate patients in permanent dentition. The average age at the time of assessment was 15.7 years. Alveolar thickness, nasoalveolar height, nasal floor ossification, and hard palate morphology were evaluated using dental, axial, and coronal cuts on computed tomographic scans and three-dimensional models. All measurements were normalized and ratios of the affected side versus the nonaffected side were provided. Volume measurements and ratios of each hemimaxilla were added. The presence or absence of the permanent lateral incisor on the cleft side was also recorded. RESULTS: Alveolar thickness and height were ideal or good, respectively, in 89.5 and 91.4 percent of the sample. Insufficient ossification (<25 percent) was found in three patients (5.2 percent), and only one of them (1.7 percent) presented no bone bridging. A statistically significant association was detected between the degree of alveolar ossification, the type of nasal floor ossification, and volume ratio. CONCLUSIONS: Early secondary gingivoalveoloplasty seemed to allow an adequate ossification of both the alveolar and nasal region. Three-dimensional evaluation of the alveolar cleft ossification provided further information on alveolar bridging and allowed evaluation of the bone availability for implant placement. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 26818329 TI - Defining Population-Specific Craniofacial Fracture Patterns and Resource Use in Geriatric Patients: A Comparative Study of Blunt Craniofacial Fractures in Geriatric versus Nongeriatric Adult Patients. AB - BACKGROUND: This study investigates the hypothesis that mechanisms of injury, fracture patterns, and burden to the health care system differ between geriatric and nongeriatric populations sustaining blunt-force craniofacial trauma. METHODS: A 5-year retrospective chart review of patient records and computed tomographic imaging was performed. Demographic and outcome data were extracted for equally numbered samples of blunt-mechanism facial fracture patients aged 60 years or older (geriatric), and adult patients aged 18 to 59 years (adult nongeriatric). Comparisons were made between these two populations using t tests and multivariable logistic regression. RESULTS: One thousand eighty-seven geriatric and 1087 nongeriatric patients were included. Geriatric patients were significantly more likely to be Caucasian, female, and have sustained fractures as the result of falling. They also had significantly longer hospital stays, were more likely to die, and were more likely to be discharged to home with services. Mandible fractures and panfacial fractures were significantly more common in the nongeriatric population. Geriatric age was associated with doubled length of hospitalization for patients with midface fractures. Logistic regression revealed that significantly higher incidences of orbital floor, maxillary, and condylar fractures in geriatric patients were dependent on geriatric age status, rather than mechanism of injury alone. CONCLUSIONS: Resource allocation for geriatric patients with craniofacial trauma should differ from that of their nongeriatric adult counterparts, with more resources allocated to supportive care during hospitalization and assistive care after discharge. The authors' data indicate that structural and biological changes in the craniofacial skeleton contribute to differences in fracture location independent of mechanism of injury. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II. PMID- 26818330 TI - Time Interval Reduction for Delayed Implant-Based Cranioplasty Reconstruction in the Setting of Previous Bone Flap Osteomyelitis. AB - BACKGROUND: Reinfections following implant-based cranioplasty, in the setting of previous bone flap osteomyelitis, are common and associated with significant morbidity. The timing of reconstruction following initial osteomyelitic bone flap removal remains controversial; most advocate for prolonged time intervals of approximately 6 to 12 months. Thus, the authors investigated their delayed cranioplasty outcomes following both early (between 90 and 179 days) and late (>= 180 days) time intervals with custom craniofacial implants to determine whether timing affected outcomes and rates of reinfection. METHODS: An institutional review board-approved retrospective cohort review of 25 consecutive cranioplasties, from 2012 to 2014, was conducted. A nonparametric bivariate analysis compared variables and complications between the two different time interval groups, defined as early cranioplasty (between 90 and 179 days) and cranioplasty (>= 180 days). RESULTS: No significant differences were found in primary and secondary outcomes in patients who underwent early versus late cranioplasty (p > 0.29). The overall reinfection rate was only 4 percent (one of 25), with the single reinfection occurring in the late group. Overall, the major complication rate was 8 percent (two of 25). Complete and subgroup analyses of specific complications yielded no significant differences between the early and late time intervals (p > 0.44). CONCLUSIONS: The results suggest that early cranioplasty is a viable treatment option for patients with previous bone flap osteomyelitis and subsequent removal. As such, a reduced time interval of 3 months--with equivalent outcomes and reinfection rates--represents a promising area for future study aiming to reduce the morbidity surrounding prolonged time intervals. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 26818331 TI - Treatment Outcome of the Transfacial Titanium Epiplating System for Total Nasal Defects. AB - BACKGROUND: Malignant tumors are the most frequent reason for acquired defects of the nose. Bone-anchored craniofacial prostheses represent a secure, uncomplicated, and cosmetically acceptable rehabilitative alternative to surgical reconstruction. The aim of this study was to determine a potential benefit of the Titanium Epiplating System (Fa. Medicon, Tuttlingen, Germany) as a grouped implant system in the anatomically difficult nasal region with limited bone supply. METHODS: Patients with complete nasal defects who received a transfacial Titanium Epiplating System between January of 2009 and December of 2013 for nasal prostheses were included. The Epiplating titanium plates are specially adapted to the nasal region and were modified individually. Implant survival, periimplantitis, clinical course, and risk factors for implant survival were assessed retrospectively, including univariate statistics. RESULTS: Fifty-three patients were included in this study. At the time of last follow-up, 51 of 53 Epiplating systems (96.2 percent) were stable in situ. One titanium plate had to be renewed because of a traumatic accident and one plate had to be removed because of disease recurrence. Periimplantitis occurred in 7.5 percent and could be treated successfully by either local or systemic antibiotic therapy without any loss of stability in bone anchorage. Only smoking significantly increased the risk of periimplantitis (p = 0.013), whereas age, irradiation, chemotherapy, and immunosuppression did not influence the outcome of therapy. The median healing time with use of the Titanium Epiplating System was 3.6 +/- 2.7 months. CONCLUSIONS: The Titanium Epiplating System is a safe and uncomplicated system for bone-anchored retention of nasal prostheses. Good aesthetic results can be achieved. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 26818332 TI - A National Study of the Impact of Initial Debridement Timing on Outcomes for Patients with Deep Sternal Wound Infection. AB - BACKGROUND: Excisional debridement for patients with deep sternal wound infection is a main component of treatment. This study aims to evaluate the impact of delayed excisional debridement on mortality and associated outcomes. METHODS: The authors analyzed the MarketScan database from 2009 to 2013 to identify patients with deep sternal wound infection who received surgical intervention. A logistic regression model was created to model mortality. Poisson regression models were used to model number of procedures, number of hospitalizations, and length of stay. A log-linear regression model was used for cost analysis. All analyses were adjusted for patient risk factors. RESULTS: The final cohort included 1335 patients with 12 percent in-hospital mortality. There was considerable variation in timing of debridement among patients with deep sternal wound infection, with more than 25 percent undergoing initial debridement 4 or more days after diagnosis, and 10 percent undergoing debridement more than 1 week after diagnosis. Patients undergoing delayed debridement had progressively higher risk for greater number of admissions and total hospital days compared with those undergoing early debridement. Patients undergoing debridement on the day of diagnosis of deep sternal wound infection had a predicted 34 total hospital days, compared with 49 total hospital days for patients undergoing debridement more than 7 days after diagnosis. CONCLUSIONS: Patients treated with early surgical intervention had fewer hospital admissions and fewer hospital days than patients undergoing delayed surgical treatment. Protocols to facilitate early debridement have the potential to improve quality and efficiency of deep sternal wound infection care. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 26818333 TI - Facial Fractures. AB - LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Demonstrate an understanding of some of the changes in aspects of facial fracture management. 2. Assess a patient presenting with facial fractures. 3. Understand indications and timing of surgery. 4. Recognize exposures of the craniomaxillofacial skeleton. 5. Identify methods for repair of typical facial fracture patterns. 6. Discuss the common complications seen with facial fractures. SUMMARY: Restoration of the facial skeleton and associated soft tissues after trauma involves accurate clinical and radiologic assessment to effectively plan a management approach for these injuries. When surgical intervention is necessary, timing, exposure, sequencing, and execution of repair are all integral to achieving the best long-term outcomes for these patients. PMID- 26818334 TI - A Real-Time Local Flaps Surgical Simulator Based on Advances in Computational Algorithms for Finite Element Models. AB - BACKGROUND: This article presents a real-time surgical simulator for teaching three- dimensional local flap concepts. Mass-spring based simulators are interactive, but they compromise accuracy and realism. Accurate finite element approaches have traditionally been too slow to permit development of a real-time simulator. METHODS: A new computational formulation of the finite element method has been applied to a simulated surgical environment. The surgical operators of retraction, incision, excision, and suturing are provided for three-dimensional operation on skin sheets and scalp flaps. A history mechanism records a user's surgical sequence. Numerical simulation was accomplished by a single small-form factor computer attached to eight inexpensive Web-based terminals at a total cost of $2100. A local flaps workshop was held for the plastic surgery residents at the University of Wisconsin hospitals. RESULTS: Various flap designs of Z-plasty, rotation, rhomboid flaps, S-plasty, and related techniques were demonstrated in three dimensions. Angle and incision segment length alteration advantages were demonstrated (e.g., opening the angle of a Z-plasty in a three-dimensional web contracture). These principles were then combined in a scalp flap model demonstrating rotation flaps, dual S-plasty, and the Dufourmentel Mouly quad rhomboid flap procedure to demonstrate optimal distribution of secondary defect closure stresses. CONCLUSIONS: A preliminary skin flap simulator has been demonstrated to be an effective teaching platform for the real-time elucidation of local flap principles. Future work will involve adaptation of the system to facial flaps, breast surgery, cleft lip, and other problems in plastic surgery as well as surgery in general. PMID- 26818335 TI - A Systematic Review of Surgical Randomized Controlled Trials: Part 2. Funding Source, Conflict of Interest, and Sample Size in Plastic Surgery. AB - BACKGROUND: The authors examined industry support, conflict of interest, and sample size in plastic surgery randomized controlled trials that compared surgical interventions. They hypothesized that industry-funded trials demonstrate statistically significant outcomes more often, and randomized controlled trials with small sample sizes report statistically significant results more frequently. METHODS: An electronic search identified randomized controlled trials published between 2000 and 2013. Independent reviewers assessed manuscripts and performed data extraction. Funding source, conflict of interest, primary outcome direction, and sample size were examined. Chi-squared and independent-samples t tests were used in the analysis. RESULTS: The search identified 173 randomized controlled trials, of which 100 (58 percent) did not acknowledge funding status. A relationship between funding source and trial outcome direction was not observed. Both funding status and conflict of interest reporting improved over time. Only 24 percent (six of 25) of industry-funded randomized controlled trials reported authors to have independent control of data and manuscript contents. The mean number of patients randomized was 73 per trial (median, 43, minimum, 3, maximum, 936). Small trials were not found to be positive more often than large trials (p = 0.87). CONCLUSIONS: Randomized controlled trials with small sample size were common; however, this provides great opportunity for the field to engage in further collaboration and produce larger, more definitive trials. Reporting of trial funding and conflict of interest is historically poor, but it greatly improved over the study period. Underreporting at author and journal levels remains a limitation when assessing the relationship between funding source and trial outcomes. Improved reporting and manuscript control should be goals that both authors and journals can actively achieve. PMID- 26818336 TI - A Critical Analysis of the 2012 Centers for Medicare and Medicaid Services Provider Use and Payment Database. AB - BACKGROUND: On April 9, 2014, the Centers for Medicare and Medicaid Services released 10 million billing records of over 880,000 physicians and other health care providers and accounts for over $1 billion in Medicare payments distributed in 2012. This action was part of an effort to improve the transparency, accountability, and affordability of the U.S. health care system. This study was performed to mine this unprecedented data set to delineate patterns of billing and reimbursement for plastic surgeons. METHODS: The Centers for Medicare and Medicaid Services Provider Utilization and Payment Database was accessed to analyze 2012 plastic surgery claims data with respect to providers and beneficiaries, services, and reimbursements. Pivot tables and other methods were used by means of Microsoft Excel. RESULTS: In 2012, a total of $133,472,772 was distributed to 3726 plastic surgery physician providers for 735 unique Healthcare Common Procedure Coding System codes for 1,399,404 procedure claims. Of specialty care, plastic surgery ranks twenty-sixth among 29 subspecialties for total Medicare payments. The average plastic surgeon was paid $35,821.58 by the Centers for Medicare and Medicaid Services in 2012. Forty-six percent of plastic surgeons did not receive reimbursement for services from Medicare. CONCLUSIONS: The release of an enormous amount of provider level claims data by the Centers for Medicare and Medicaid Services may serve as a new tool for locating potential fraud, pinpointing needs, and assessing levels of growth in care. Plastic surgeons need to understand implications of changes to Medicare, which will likely affect patient mix, physician documentation, billing, coding, reimbursement, and active participation in quality reporting. PMID- 26818337 TI - Criteria for the Use of the SIEA Flap for Breast Reconstruction. PMID- 26818338 TI - Reply: SIEA versus DIEP Arterial Complications: A Cohort Study. PMID- 26818339 TI - Lower Body Lift after Massive Weight Loss: Autoaugmentation versus No Augmentation. PMID- 26818340 TI - Reply: Lower Body Lift after Massive Weight Loss: Autoaugmentation versus No Augmentation [corrected]. PMID- 26818341 TI - The Limitations of Using a National Database to Investigate Risk Factors for Venous Thromboembolism. PMID- 26818342 TI - Reply: Venous Thromboembolism in Body Contouring: An Analysis of 17,774 Patients from the National Surgical Quality Improvement Databases. PMID- 26818343 TI - HSP90 and TLR4 Interplay in Keloids. PMID- 26818344 TI - Reply: Heat Shock Protein 90 Inhibitor (17-AAG) Induces Apoptosis and Decreases Cell Migration Motility of Keloid Fibroblasts. PMID- 26818345 TI - Contemporary Solutions for the Treatment of Facial Nerve Paralysis. PMID- 26818346 TI - Biomechanical and Safety Testing of a Simplified Negative-Pressure Wound Therapy Device. PMID- 26818347 TI - Reply: Biomechanical and Safety Testing of a Simplified Negative-Pressure Wound Therapy Device. PMID- 26818348 TI - So ... Are You Failing the Marshmallow Test? Connecting and Disconnecting in Our Information-Rich World. PMID- 26818349 TI - Technology and Plastic Surgery: Potential Pitfalls for Patient Confidentiality and Proposed Solutions. PMID- 26818350 TI - Reply: Technology and Plastic Surgery: Potential Pitfalls for Patient Confidentiality and Proposed Solutions. PMID- 26818351 TI - Financial Conflicts of Interest in Plastic Surgery: Background, Potential for Bias, Disclosure, and Transparency. PMID- 26818352 TI - Reply: Financial Conflicts of Interest in Plastic Surgery: Background, Potential for Bias, Disclosure, and Transparency. PMID- 26818353 TI - The Importance of Linguistics and Science When Addressing the Social Issues of Residents. PMID- 26818354 TI - Reply: Social Problems in Plastic Surgery Residents: A Management Perspective. PMID- 26818356 TI - [Diplopia 10 years after scleral buckling surgery]. PMID- 26818355 TI - The Association between Educational Attainment and Patterns of Emergency Department Utilization among Adults with Sickle Cell Disease. AB - PURPOSE: Patients with low educational attainment may be at increased risk for unplanned health care utilization. This study aimed to determine what factors are related to emergency department (ED) visits in hopes of guiding treatments and early interventions. METHODS: At two medical centers in the Mid-Atlantic United States, 258 adults with sickle cell disease aged 19-70 years participated in a retrospective study where we examined whether education level is independently associated with ED visits after accounting for other socioeconomic status (SES) variables, such as pain and disease severity and psychosocial functioning. RESULTS: The data showed that patients without a high school education visited the ED three times as frequently as patients with post secondary education. Controlling for poverty and employment status decreased the effect of education on ED visits by 33.24 %. Further controlling for disease severity and/or psychosocial functioning could not account for the remaining association between education and ED visits, suggesting that education is independently associated with potentially avoidable emergency care. CONCLUSIONS: Early interventions addressing disparities in academic performance, especially for those children most at risk, may lead to improved long-term health outcomes in this population. PMID- 26818357 TI - The feedback loop between miR-124 and TGF-beta pathway plays a significant role in non-small cell lung cancer metastasis. AB - Increasing evidence shows that micro RNAs (miRNAs) play a critical role in tumor development. However, the role of miRNAs in non-small cell lung cancer (NSCLC) metastasis remains largely unknown. Here, we found that miR-124 expression was significantly impaired in NSCLC tissues and associated with its metastasis. In vitro and in vivo experiments indicate that restoring miR-124 expression in NSCLC cells had a marked effect on reducing cell migration, invasion and metastasis. Mechanistic analyses show that Smad4, a cobinding protein in transforming growth factor-beta (TGF-beta) pathway, was identified as a new target gene of miR-124. Restoring Smad4 expression in miR-124-infected cells could partially rescue miR 124-induced abolition of cell migration and invasion. Notably, upon TGF-beta stimulation, phosphorylation of Smad2/3 was modulated by alteration of miR-124 or Smad4 expression, followed by inducing some special transcription of downstream genes including Snail, Slug and ZEB2, all of which may trigger epithelial mesenchymal transition and be associated with NSCLC metastasis. Moreover, activation of TGF-beta pathway may enhance expression of DNMT3a, leading to hypermethylation on miR-124 promoter. Therefore, heavily loss of miR-124 expression further enhances Smad4 level by this feedback loop. Taken together, our data show for the first time that the feedback loop between miR-124 and TGF beta pathway may play a significant role in NSCLC metastasis. Targeting the loop may prove beneficial to prevent metastasis and provide a more effective therapeutic strategy for NSCLC. PMID- 26818359 TI - Editorial: Pressure ulcer prevention: is it time to accept the need for universal precautions. PMID- 26818358 TI - Genetic determinants of CYP2A6 activity across racial/ethnic groups with different risks of lung cancer and effect on their smoking intensity. AB - Genetic variation in cytochrome P450 2A6 (CYP2A6) gene is the primary contributor to the intraindividual and interindividual differences in nicotine metabolism and has been found to influence smoking intensity. However, no study has evaluated the relationship between CYP2A6 genetic variants and the CYP2A6 activity ratio (total 3-hydroxycotinine/cotinine) and their influence on smoking intensity [total nicotine equivalents (TNE)], across five racial/ethnic groups found to have disparate rates of lung cancer. This study genotyped 10 known functional CYP2A6 genetic or copy number variants in 2115 current smokers from the multiethnic cohort study [African Americans (AA) = 350, Native Hawaiians (NH) = 288, Whites = 413, Latinos (LA) = 437 and Japanese Americans (JA) = 627] to conduct such an investigation. Here, we found that LA had the highest CYP2A6 activity followed by Whites, AA, NH and JA, who had the lowest levels. Adjusting for age, sex, race/ethnicity and body mass index, we found that CYP2A6 diplotypes were predictive of TNE levels, particularly in AA and JA (P trend < 0.0001). However, only in JA did the association remain after accounting for cigarettes per day. Also, it is only in this population that the lower activity ratio supports lower TNE levels, carcinogen exposure and thereby lower risk of lung cancer. Despite the association between nicotine metabolism (CYP2A6 activity phenotype and diplotypes) and smoking intensity (TNE), CYP2A6 levels did not correlate with the higher TNE levels found in AA nor the lower TNE levels found in LA, suggesting that other factors may influence smoking dose in these populations. Therefore, further study in these populations is recommended. PMID- 26818360 TI - Systematic review: what interventions improve dignity for older patients in hospital? AB - AIMS AND OBJECTIVES: To review the evidence for interventions to improve dignity for older patients in acute care. BACKGROUND: High profile cases have highlighted failure to provide dignified care for older people in hospitals. There is good evidence on what older people consider is important for dignified care and abundant recommendations on improving dignity, but it is unclear which interventions are effective. DESIGN: Narrative systematic review. METHODS: The Cochrane library, MEDLINE, EMBASE, CINAHL, BNI and HMIC electronic databases were searched for intervention studies of any design aiming to improve inpatients' dignity. The main population of interest was older patients, but the search included all patients. Studies that focused on 'dignity therapy' were excluded. RESULTS: There were no intervention studies found in any country which aimed to improve patient dignity in hospitals which included evaluation of the effect. A narrative overview of papers that described implementing dignity interventions in practice but included no formal evaluation was, therefore, undertaken. Five papers were identified. Three themes were identified: knowing the person; partnership between older people and health care professionals; and, effective communication and clinical leadership. The effect on dignity of improving these is untested. CONCLUSIONS: There are currently no studies that have tested interventions to improve the dignity of older people (nor anyone else) in hospitals. Further research using well designed trials of interventions is needed. There is also a need to develop and validate outcome measures for interventions to improve dignity. RELEVANCE TO CLINICAL PRACTICE: At present nurses lack robust evidence on how to improve dignity. There is ample evidence on what undermines patients' dignity and there is a need to develop and test interventions designed to improve patient dignity. PMID- 26818361 TI - The use of evidenced-based information by nurses and midwives to inform practice. AB - AIMS AND OBJECTIVES: To examine the implementation of evidence-based information by nurses and midwives to inform their practice. BACKGROUND: It is widely recognised that the main benefits of using evidence-based information are to improve and update clinical practice and to enhance the quality of care and outcomes for patients. However, despite a large body of research showing that nurses and midwives have positive attitudes towards evidence-based practice , its implementation remains a considerable and significant challenge. DESIGN: This was a cross-sectional on-line survey. METHODS: A self-completed questionnaire was used to collect data from a convenience sample of 386 nursing and midwifery diplomates and graduates from June-December 2013. One hundred and seventy-two participants completed the questionnaire, giving a response rate of 44.6%. RESULTS/FINDINGS: The majority of respondents expressed very positive attitude towards evidence-based practice and nearly everyone felt that this should become an important part of daily practice. A significant number stated that they have regular access to research through a number of relevant databases and the Internet at their place of work and evidence-based guidelines relevant to their speciality were also available. The two top barriers perceived by respondents were lack of time to search for relevant evidence-based information and being able to make time during working hours to look for new information. The most popular strategy suggested was to ensure evidence-based information is readily available in a form which nurses and midwives can easily understand the implications for their practice. CONCLUSION: Health services and government agencies should make a concerted effort to make time for nurses and midwives to access, appraise and use evidence-based information to inform practice. RELEVANCE TO CLINICAL PRACTICE: More resources including protected time should be made available to support nurses and midwives to use evidence-based information to improve the quality of care provided. PMID- 26818362 TI - Short-term intervention to reduce anxiety before coronary artery bypass surgery- a randomised controlled trial. AB - AIMS AND OBJECTIVES: The aim of this study was to evaluate an intervention with individualised information and emotional support before coronary artery bypass grafting in a controlled randomised trial. BACKGROUND: Anxiety is a typical phenomenon in patients who are to undergo cardiac surgery. Preoperative anxiety has been shown to correlate to adverse postoperative outcomes. Emotional support could be an effective measure to reduce preoperative anxiety. DESIGN AND METHODS: Patients with planned first coronary artery bypass grafting were randomised into an intervention group (n = 139) and a control group (n = 114). The patients of the control group were routinely informed as usual. The patients of the intervention group received a dialogue with individualised information and emotional support one day before surgery in addition to standard care. This intervention of ~30 minutes was based on a supportive psychotherapy model and was delivered by trained nurses. The primary outcome was the change in anxiety before operation. The secondary outcomes consisted of changes in postoperative anxiety, time on intensive care unit and in-hospital mortality. RESULTS: Significantly reduced anxiety was found in the intervention group patients compared to control patients before coronary artery bypass grafting (p < 0.001) and five days after surgery (p < 0.001). Both groups did not differ in in-hospital mortality and duration of stay in the intensive care unit. CONCLUSIONS: Our short-term psychosocial intervention in patients undergoing coronary artery bypass grafting had a beneficial effect on reducing pre- and postoperative anxiety that was better than routine information alone. RELEVANCE TO CLINICAL PRACTICE: These results advocate training for nurses and physicians to provide emotional support to patients before coronary artery bypass grafting. PMID- 26818363 TI - On duty all the time: health and quality of life among immigrant parents caring for a child with complex health needs. AB - AIMS AND OBJECTIVES: To provide knowledge about how immigrant parents of children with complex health needs manage their family lives and how this affects their own health and quality of life. BACKGROUND: Caregivers of children with complex health needs have additional risk for general health problems and mental health problems and immigrant parents may be more vulnerable to mental distress and failing health and quality of life. DESIGN: This qualitative study used an exploratory design with individual and focus group interviews. Data collection and analysis followed phenomenological hermeneutic guidelines. METHODS: Individual and group interviews with 27 parents: 18 mothers and 9 fathers from Pakistan, Poland and Vietnam. RESULTS: Immigrant parents of children with complex health needs experience their own health and quality of life challenges. They described the burden of dealing with their child's needs and special care, which affects their sleep and physical and mental health. Single mothers are particularly vulnerable. CONCLUSION: Parents reported positive and negative effects of their caregiving experience that may affect their health and quality of life. Mothers were the primary caregivers and reported more health problems than did fathers. The lack of respite care, social networks and support impacted maternal health. Immigrant parents struggle to access resources for their child with complex health needs. RELEVANCE TO CLINICAL PRACTICE: Hospital nurses, schools and community health care can play a valuable role in supporting the parents of children with complex health needs. It is important that parents are informed about their rights and receive a coordinator and interdisciplinary group to ensure that their needs are met with assistance and respite care. That maternal health was worse in this sample implies that health care professionals should pay more attention to reducing stress among these caregivers. PMID- 26818364 TI - The effect of sucrose as pain relief/comfort during immunisation of 15-month-old children in health care centres: a randomised controlled trial. AB - AIMS AND OBJECTIVES: To investigate the effect of 30% sucrose compared with a placebo (water) as pain relief and comfort during immunisation of 15-month-old children in health care centres. BACKGROUND: Children experience different levels of pain and distress during immunisation. Sweet solutions function as pain relief during immunisation for infants up to one year of age. However, there are few studies of older children. DESIGN: An experimental design in which the participants (15-month-old infants) were randomly assigned to an intervention group that received a 30% sugar solution or a control group that received a placebo (water). METHODS: The study was performed at three health care centres in a large Norwegian municipality. The parents of all 15-month-old infants who were recommended for vaccination (for measles, mumps and rubella) between 5 September 2013 and 31 March 2014 were invited to have their infant participate. Duration of crying was the outcome measure. RESULTS: A total of 114 children were included (59 in the intervention group, 55 in the control group). The intervention group infants' crying was shorter (18 seconds mean) compared with the control group infants (33 seconds mean). The difference in crying duration between the groups was both statistically and clinically significant. CONCLUSION: This trial revealed that 30% sucrose orally has a calming and pain-relieving effect on 15 month-old infants during immunisation. RELEVANCE TO CLINICAL PRACTICE: Public health nurses should use a 30% sucrose solution for pain relief during immunisation of 15-month-old infants. PMID- 26818365 TI - Tracking the footsteps: a constructivist grounded theory of the clinical reasoning processes that registered nurses use to recognise delirium. AB - AIMS AND OBJECTIVES: To construct a grounded theory that explains the clinical reasoning processes that registered nurses use to recognise delirium while caring for older adults in acute care settings. BACKGROUND: Delirium is often under recognised in acute care settings; this may stem from underdeveloped clinical reasoning processes. Little is known about registered nurses' clinical reasoning processes in complex situations such as delirium recognition. DESIGN: Seventeen registered nurses working in acute care settings were interviewed. Concurrent data collection and analysis, constant comparative analysis and theoretical sampling were conducted in 2013-2014. METHODS: A grounded theory approach was used to analyse interview data about the clinical reasoning processes of registered nurse in acute hospital settings. RESULTS: The core category that emerged from data was 'Tracking the footsteps'. This refers to the common clinical reasoning processes that registered nurses in this study used to recognise delirium in older adults in acute care settings. It depicted the process of continuously trying to catch the state of delirium in older adults. CONCLUSIONS: Understanding the clinical reasoning processes that contribute to delirium under-recognition provides a strategy by which this problem can be brought to the forefront of awareness and intervention by registered nurses. RELEVANCE TO CLINICAL PRACTICE: Registered nurses could draw from the various processes identified in this research to develop their clinical reasoning practice to enhance their effective assessment strategies. Delirium recognition by registered nurses will contribute to quality care to older adults. PMID- 26818366 TI - Family members' lived experiences of everyday life after intensive care treatment of a loved one: a phenomenological hermeneutical study. AB - AIMS AND OBJECTIVES: To illuminate relatives' experiences of everyday life after a loved one's stay in an intensive care unit. BACKGROUND: Relatives of intensive care patients experience considerable stress that can have a long-lasting effect on their everyday lives. Relatives frequently report anxiety, depression and complicated grief as a result of their experiences in the intensive care unit. DESIGN: A qualitative design was chosen. METHODS: Thirteen relatives were interviewed 3 months to 1 year after the discharge or death of an intensive care unit patient. A phenomenological hermeneutical method was used to explore family members' lived experiences upon returning home after their loved ones' stay in the intensive care unit. RESULTS: Two themes emerged from the analysis of the data: (1) changes in everyday life and emotional reactions, and (2) managing changes and need of support and follow-up from the ICU. CONCLUSIONS: Family members experience changes in emotions, roles and responsibilities after returning home. They must maintain control of themselves and adapt to the changes to face the future. They cope by using their personal resources and support from others. Some are in further need of follow-up from the intensive care unit staff. RELEVANCE TO CLINICAL PRACTICE: Nursing education could focus increasingly more on the significance of communication and personal support, which helps family members cope during patients' stay and experience a sense of personal strength when returning home. Further research should address how to identify and support those with special needs after the intensive care unit stay. PMID- 26818367 TI - Stroke among African-Caribbean women: lay beliefs of risks and causes. AB - AIMS AND OBJECTIVES: To investigate African Caribbean women's subjective accounts of stroke and how this impacted on their lives and identify beliefs attributed to the causes of stroke in this post stroke. BACKGROUND: In the UK, those from African or African Caribbean ethnicity are at an increased risk of stroke, and stroke risks are double that of the UK White population. This is because diabetes and hypertension are more common in those of African and African Caribbean ethnic groups. The main risk factors for stroke are high blood pressure, alongside obesity and overweight, poor diet and lack of physical activity. DESIGN: A qualitative study using interpretative phenomenological analysis. METHODS: Data were collected via semi-structured indepth interviews for six African Caribbean women. Interviews were audio recorded and transcribed verbatim. Interpretative Phenomenological Analysis was used to deconstruct the data and facilitate developing themes. RESULTS: Six semi-structured interviews were completed with women aged 47-85 years. Two themes emerged (1) the role of lifestyle and biological risk factors linked to the causes of stroke and (2) the role of spirituality, in identifying the lay beliefs and causes of stroke. CONCLUSION: Alternative explanations of the causes of stroke that include witchcraft, or wishing someone wrong suggests a lack of perceived control over stroke. This may suggest a focus on less visible risk factors such as hypertension, familial history or diabetes and will need inclusion in health promotion materials. Lay beliefs such as witchcraft can co-exist amicably alongside modern medicine, as long as they do not hinder access to medication, treatment or risk factor management of stroke. RELEVANCE TO CLINICAL PRACTICE: The results demonstrated that nursing care and health promotion materials should emphasise on obesity, overweight and management of these through diet and physical activity to prevent stroke occurring. PMID- 26818368 TI - Prefrailty in community-dwelling older adults is associated with nutrition status. AB - AIMS AND OBJECTIVES: This study investigated the differences of demographic characteristics and nutrition status between prefrail and nonfrail older adults. Meanwhile, the factors related to the nutrition status of community-dwelling older adults were also studied. BACKGROUND: The World Health Organisation has actively developed prevention programmes to address geriatric frailty. However, few previous studies have focused on the relationship between prefrailty and nutrition status. DESIGN: This study adopted a cross-sectional and correlational research design. METHODS: Community-dwelling older adults were recruited for this study. The participants' nutrition status was assessed using the Mini-Nutritional Assessment tool, and their frailty status was evaluated based on the Study of Osteoporotic Fractures indicators. The Study of Osteoporotic Fractures criteria comprise the following three items: >5% loss in total body weight within one year; inability to rise five times from a chair without assistance and a self reported lack of energy. Inclusion criteria were age >=65 years, living independently at home and exhibiting neither mental impairment nor acute disease. RESULTS: Data were gathered from 152 participants; most were men, lived alone and had a level of education lower than elementary school. Multiple linear regressions were used to evaluate the association between variables and nutritional status, the results of which revealed that prefrailty and body mass index were independently related to the participants' nutrition status. CONCLUSIONS: The results showed that nutritional assessment can be employed with community-dwelling older adults. In particular, prefrailty and body mass index were key factors that affected nutritional status in older adults. RELEVANCE TO CLINICAL PRACTICE: Community nurses must understand the risk factors related to nutritional status in community-dwelling older people. If nurses use this approach, prefrail older adults are likely to experience improved confidence in maintaining their health and a decreased incidence of frailty and malnutrition. PMID- 26818369 TI - Understanding nurses' decision-making when managing weaning from mechanical ventilation: a study of novice and experienced critical care nurses in Scotland and Greece. AB - AIM AND OBJECTIVES: To examine how nurses collect and use cues from respiratory assessment to inform their decisions as they wean patients from ventilatory support. BACKGROUND: Prompt and accurate identification of the patient's ability to sustain reduction of ventilatory support has the potential to increase the likelihood of successful weaning. Nurses' information processing during the weaning from mechanical ventilation has not been well-described. DESIGN: A descriptive ethnographic study exploring critical care nurses' decision-making processes when weaning mechanically ventilated patients from ventilatory support in the real setting. METHODS: Novice and expert Scottish and Greek nurses from two tertiary intensive care units were observed in real practice of weaning mechanical ventilation and were invited to participate in reflective interviews near the end of their shift. Data were analysed thematically using concept maps based on information processing theory. Ethics approval and informed consent were obtained. RESULTS: Scottish and Greek critical care nurses acquired patient centred objective physiological and subjective information from respiratory assessment and previous knowledge of the patient, which they clustered around seven concepts descriptive of the patient's ability to wean. Less experienced nurses required more encounters of cues to attain the concepts with certainty. Subjective criteria were intuitively derived from previous knowledge of patients' responses to changes of ventilatory support. All nurses used focusing decision making strategies to select and group cues in order to categorise information with certainty and reduce the mental strain of the decision task. CONCLUSIONS: Nurses used patient-centred information to make a judgment about the patients' ability to wean. Decision-making strategies that involve categorisation of patient-centred information can be taught in bespoke educational programmes for mechanical ventilation and weaning. RELEVANCE TO CLINICAL PRACTICE: Advanced clinical reasoning skills and accurate detection of cues in respiratory assessment by critical care nurses will ensure optimum patient management in weaning mechanical ventilation. PMID- 26818371 TI - 'Living with tics': self-experience of adolescents with Tourette syndrome during peer interaction. AB - AIMS AND OBJECTIVES: To describe the essence of the self-experience of adolescents with Tourette syndrome in the context of peer interaction. BACKGROUND: Tourette syndrome has an adverse impact on adolescents' physical, psychological and interpersonal interactions. Peers provide adolescents with social interactions that are crucial to the formation of self-identity. Studies exploring the self-experience of adolescents with Tourette syndrome in the context of peer relationships are lacking. DESIGN: A qualitative, phenomenological research design was used. METHODS: A total of 12 adolescents with Tourette syndrome from the Taiwan Tourette Family Association were selected by purposive sampling. Data were collected using open-ended questions in one-on one in-depth interviews that lasted 60-90 minutes. Giorgi's phenomenological methods were applied to analyse the data obtained. Four criteria were employed to evaluate methodological rigour. RESULTS: The findings showed that the self experience of adolescents with Tourette syndrome during peer interaction reflected their lived experiences of peer identity, social identity and self identity. Themes included: (1) the inexplicable onset of tics during encounters with other people, (2) sources inspiring the courage for self-acceptance and (3) strategies of self-protection in response to changes in situation. CONCLUSIONS: The self-experience of peer interaction among adolescents with Tourette syndrome is a dynamic and interactive process characterised by the symbolic meanings conferred on the tics by the interacting adolescents. The adolescents with Tourette syndrome obtain self-identity through peer responses and recognition, while the tolerance, respect and support of parents and teachers spark the adolescents' courage for self-acceptance. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers who assist adolescents with Tourette syndrome must understand that tics occur in the context of peer interaction and how this affects the adolescents' relationships with their peers in various life situations. Furthermore, healthcare providers should provide support, respect and offer coping strategies regarding peer interaction based on an understanding of the social dynamics of such peer interactions. PMID- 26818370 TI - Communication between office-based primary care providers and nurses working within patients' homes: an analysis of process data from CAPABLE. AB - AIMS AND OBJECTIVES: To examine themes of communication between office-based primary care providers and nurses working in private residences; to assess which methods of communication elicit fruitful responses to nurses' concerns. BACKGROUND: Lack of effective communication between home health care nurses and primary care providers contributes to clinical errors, inefficient care delivery and decreased patient safety. Few studies have described best practices related to frequency, methods and reasons for communication between community-based nurses and primary care providers. DESIGN: Secondary analysis of process data from 'Community Aging in Place: Advancing Better Living for Elders (CAPABLE)'. METHODS: Independent reviewers analysed nurse documentation of communication (phone calls, letters and client coaching) initiated for 70 patients and analysed 45 letters to primary care providers to identify common concerns and recommendations raised by CAPABLE nurses. RESULTS: Primary care providers responded to 86% of phone calls, 56% of letters and 50% of client coaching efforts. Primary care providers addressed 86% of concerns communicated by phone, 34% of concerns communicated by letter and 41% of client-raised concerns. Nurses' letters addressed five key concerns: medication safety, pain, change in activities of daily living, fall safety and mental health. In letters, CAPABLE nurses recommended 58 interventions: medication change; referral to a specialist; patient education; and further diagnostic evaluation. CONCLUSIONS: Effective communication between home-based nurses and primary care providers enhances care coordination and improves outcomes for home-dwelling elders. Various methods of contact show promise for addressing specific communication needs. RELEVANCE TO CLINICAL PRACTICE: Nurses practicing within patients' homes can improve care coordination by using phone calls to address minor matters and written letters for detailed communication. Future research should explore implementation of Situation, Background, Assessment and Recommendation in home care to promote safe and efficient communication. Nurses should empower patients to address concerns directly with providers through use of devices including health passports. PMID- 26818372 TI - A feasibility and efficacy randomised controlled trial of swaddling for controlling procedural pain in preterm infants. AB - AIMS AND OBJECTIVES: This study aimed to investigate the feasibility and efficacy of swaddling to control procedural pain among preterm infants. BACKGROUND: Swaddling has been recommended for controlling neonatal pain. However, the feasibility for use is uncertain and insufficient evidence is available among preterm infants. DESIGN: A two-arm randomised controlled trial with repeated measures. METHOD: The study was conducted in a 21-bed neonatal intensive care unit of a regional hospital in Hong Kong. Preterm infants who required heelstick procedure were eligible. Fifty-four preterm infants between 30-37 gestational weeks were randomly assigned to swaddling (n = 27) and control (standard care, n = 27) groups. Pain assessment was performed pre, during, immediate, two, four, six and eight minutes after heelstick procedure using the Premature Infant Pain Profile. RESULTS: The mean Premature Infant Pain Profile scores were significantly reduced in the intervention group compared to the control group during, immediate, two, four, and six minutes after the heelstick procedure. The mean changes of heart rate and oxygen saturation in the intervention group were significantly lower than that of the control group at all measured time points. Notably, the swaddled infants quickly resumed to the baseline level at two minutes whereas the control group reached the stable state at an extended period of six minutes. CONCLUSION: The findings show that swaddling is feasible and efficacious in controlling pain for heelstick procedure among preterm infants. No adverse effects were observed. RELEVANCE TO CLINICAL PRACTICE: This article presents the feasibility and efficacy of swaddling as a non-pharmacological and non-invasive intervention to relieve pain during the heelstick procedures among preterm infants. Swaddling can contribute to control minor procedural pain in neonates as one of the simple, safe, cost effective, humanistic and natural analgesia alternatives. PMID- 26818373 TI - Undefined and unpredictable responsibility: a focus group study of the experiences of informal caregiver spouses of patients with severe COPD. AB - AIMS AND OBJECTIVES: To explore how spouses of patients with severe chronic obstructive pulmonary disease experience their role as informal caregiver. BACKGROUND: Informal caregiver spouses are of pivotal importance in the way that patients with chronic obstructive pulmonary disease cope with their daily life, including their opportunity to stay at home and avoid hospitalisations in the last stages of the disease. However, caregiving is associated with increased morbidity and mortality among caregivers. Further understanding of the role as an informal caregiver spouse of patients with severe chronic obstructive pulmonary disease is needed to develop supportive interventions aimed at reducing the caregiver burden. DESIGN: The study had a qualitative exploratory design. The data collection and analysis were based on framework method. Framework method is a thematic methodology and consists of five key stages: familiarisation, identifying a thematic framework, indexing, charting and mapping & interpretation. METHODS: Three focus groups were conducted in November 2013 with 22 spouses of patients with severe chronic obstructive pulmonary disease. RESULTS: Undefined and unpredictable responsibility was found to be the overarching theme describing the informal caregiver role. Underlying themes were: being constantly in a state of alertness, social life modified, maintaining normality, ambivalence in the relationship and a willingness to be involved. CONCLUSIONS: The informal caregiver spouses experienced ambiguity about expectations from their private and the health professionals' surroundings. The informal caregiver spouses wanted to provide meaningful care for their partners, but sought knowledge and support from the health professionals. RELEVANCE TO CLINICAL PRACTICE: We recommend that nurses take on the responsibility for including the informal caregiver spouses in those aspects of decision-making that involve the common life of the patients and their spouses. PMID- 26818374 TI - Experiences of Spanish women undergoing hysterosalpingography as part of the infertility process: a phenomenological study. AB - AIMS AND OBJECTIVES: To describe and understand the experiences and perceptions of women who undergo hysterosalpingography as part of the infertility process. BACKGROUND: Nurses and midwives should conduct research into the emotional aspects of caring for patients undergoing infertility treatment. The hysterosalpingography is considered to be the most feared test in the infertility process and the one about which very little is known. DESIGN: A phenomenological qualitative study. METHODS: Ten Spanish women who had undergone hysterosalpingography participated in this study. In-depth interviews were carried out between October 2012-May 2013. Data analysis was performed with the help of atlas.ti software to identify emerging themes. RESULTS: The experience of the participants who underwent hysterosalpingography during the infertility process is represented by the following three themes: (1) becoming a mother to feel complete as a person and as a woman, with the subthemes 'maternity as a life objective' and 'maternity in terms of gender identity'; (2) infertility--an intimate experience which provokes negative feelings, with the subthemes 'negative feelings regarding own infertility' and 'infertility as an experience that is little shared with others'; (3) Undergoing hysterosalpingography, with the subthemes 'feelings regarding hysterosalpingography', 'treatment by medical providers' and 'areas for improvement regarding the service given by the providers'. CONCLUSION: For women who undergo hysterosalpingography, maternity may be seen as a life objective that could identify them as women. Results suggest that although infertility is experienced with negative feelings such as anxiety, frustration and sadness, hysterosalpingography seems to be related with both hope and fear when facing the test. RELEVANCE TO CLINICAL PRACTICE: Knowing the experiences of these women could help nurses, midwives and physicians to provide better patient-centred care. PMID- 26818375 TI - Developing Evidence-Based Practice questionnaire for community health nurses: reliability and validity of a Spanish adaptation. AB - AIMS AND OBJECTIVES: This study aimed to translate the community nursing version of the Developing Evidence-Based Practice questionnaire, adapt the Spanish translation to the primary care context in Spain, and evaluate its reliability and validity. BACKGROUND: Instruments available in Spanish to date are not designed to rigorously evaluate barriers and incentives associated with evidence based practice implementation in community health nursing. DESIGN: Classical Test Theory approach. METHODS: The 49-item Developing Evidence-Based Practice questionnaire was translated, back-translated and pilot-tested. Two items were added to assess respondents' ability to read and understand the English language. During the first six months of 2010, 513 nurses from 255 primary health care centres in Catalunya (Spain) voluntarily participated in the study. Internal consistency and test-retest reliability were evaluated. Internal structure was analysed by principal component analysis. A randomized, controlled, parallel design study was carried out to test scores' sensitivity to change with two groups, intervention and control. The intervention consisted of eight hours of in person training, provided by experts in evidence-based practice. RESULTS: Of 513 nurses, 445 (86.7%) nurses responded to all 51 items. Factor analysis showed six components that explained 51% of the total variance. Internal consistency and test-retest reliability were satisfactory (Cronbach alpha and intraclass correlation coefficients >0.70). A total of 93 nurses participated in the sensitivity-to-change tests (42 in the intervention group, 51 controls). After the training session, overall score and the 'skills for evidence-based practice' component score showed a medium (Cohen d = 0.69) and large effect (Cohen d = 0.86), respectively. CONCLUSIONS: The Developing Evidence-Based Practice questionnaire adapted to community health nursing in the primary care setting in Spain has satisfactory psychometric properties. RELEVANCE TO CLINICAL PRACTICE: The Developing Evidence-Based Practice questionnaire is a useful tool for planning and evaluating the implementation of evidence-based practice in community health nursing. PMID- 26818376 TI - Effects of gum chewing on abdominal discomfort, nausea, vomiting and intake adherence to polyethylene glycol solution of patients in colonoscopy preparation. AB - AIMS AND OBJECTIVE: This study aimed to reduce the common discomfort of colonoscopy patients when taking a bowel cleansing solution. Gum chewing, a form of sham feeding, was examined as a possible efficient intervention to reduce the discomfort from consuming polyethylene glycol. BACKGROUND: Sham feeding is a method that is similar to food intake, which stimulates the cephalic-vagal reflex, promotes secretion of gastrointestinal hormones, and stimulates movement of the gastrointestinal tract. Sham feeding with chewing gum has been shown to promote bowel motility. DESIGN: This was an experimental study utilising a randomised control group post-test design. METHODS: This study was conducted in Seoul, Korea from August-October 2012. Patients were randomly allocated into two groups; a gum-chewing group (n = 66) or a control group (n = 65). In the control group, patients drank a polyethylene glycol solution according to the general protocol. For the gum-chewing group, patients had to chew one stick of sugarless gum during the pause interval of drinking the polyethylene glycol solution. Results were analysed using the Mann-Whitney U-test, t-test, Chi-square test or Fisher's exact test. RESULTS: The gum-chewing group reported significantly lower abdominal discomfort, nausea and vomiting and took a shorter time to ingest the polyethylene glycol solution than the control group. CONCLUSION: Gum chewing is efficient in improving abdominal discomfort, nausea, vomiting and the intake adherence of patients in colonoscopy preparation. RELEVANCE TO CLINICAL PRACTICE: Gum chewing was demonstrated by this study to be a potentially effective nursing intervention that is easy for patients to perform with simple instructions and is low cost with no side effects. PMID- 26818377 TI - Illness perceptions of fatigue and the association with sense of coherence and stress in patients one year after myocardial infarction. AB - AIMS AND OBJECTIVES: To explore the associations between illness perceptions of fatigue, sense of coherence and stress in patients one year after myocardial infarction. BACKGROUND: Post-myocardial infarction fatigue is a stressful symptom that is difficult to cope with. Patients' illness perceptions of fatigue guide professionals in predicting how individuals will respond emotionally and cognitively to symptoms. Individuals' sense of coherence can be seen as a coping resource in managing stressors. DESIGN: A cross-sectional study design was used. METHOD: One year post-myocardial infarction, a total of 74 patients still experiencing fatigue completed four questionnaires: the Multidimensional Fatigue Scale Inventory-20, the Brief Illness Perception Questionnaire, the Sense of Coherence scale (sense of coherence-13) and a single-item measure of stress symptoms. Descriptive statistics, correlations and stepwise regression analysis were carried out. RESULTS: Strong negative associations were found between illness perceptions of fatigue, sense of coherence and stress. Sense of coherence has an impact on illness perceptions of fatigue. Of the dimensions of sense of coherence, comprehensibility seemed to play the greatest role in explaining illness perceptions of fatigue one year after myocardial infarction. CONCLUSION: To strengthen patients' coping resources, health-care professionals should create opportunities for patients to gain individual-level knowledge that allows them to distinguish between common fatigue symptoms and warning signs for myocardial infarction. RELEVANCE TO CLINICAL PRACTICE: There is a need to improve strategies for coping with fatigue. It is also essential to identify patients with fatigue after myocardial infarction, as they need explanations for their symptoms and extra support. PMID- 26818378 TI - The experiences of family carers in the delivery of invasive clinical interventions for young people with complex intellectual disabilities: policy disconnect or policy opportunity? AB - AIMS AND OBJECTIVES: To explore the experiences of family carers in the delivery of invasive clinical interventions within community settings. BACKGROUND: Many young people with intellectual disabilities present with complex health needs and require clinical interventions to sustain life. As the population lives into older age there is growing demand for the delivery of these interventions within the community setting. DESIGN: An interpretivist qualitative design. METHODS: Ten family carers of children with intellectual disabilities and complex care needs requiring invasive clinical interventions participated in semi-structured interviews. RESULTS: There are barriers identified regarding the delivery of invasive clinical interventions in the home setting by social care support workers. These include a reluctance to carry out invasive clinical interventions both for family carers and staff, anxiety, a lack of knowledge and training and difficulties in recruiting appropriate staff. CONCLUSIONS: There needs to be strategic policy developments focusing on this population who are cared for in the community and require invasive clinical interventions. RELEVANCE TO CLINICAL PRACTICE: Registered Nurses have a key role in educating and preparing families and social care support workers to safely deliver invasive clinical interventions in community settings for both children and adults with intellectual disabilities. PMID- 26818379 TI - Effects of a strengths-based perspective support group among Taiwanese women who left a violent intimate partner relationship. AB - AIMS AND OBJECTIVES: To examine the effects of an 8-week strengths-based perspective group intervention on hope, resilience and depression in Taiwanese women who left a violent intimate partner relationship. BACKGROUND: Studies on interventions for abused women have primarily focused on psychological problems. However, the effect of group intervention on the psychological strengths of abused women is still unknown. DESIGN: A two-group, quasi-experimental design using repeated measures was used in this study. METHODS: Twenty-nine Taiwanese women who left violent intimate partner relationships were assigned to two groups and five participants did not complete the study. The experimental group (n = 8) underwent an 8-week strengths-based perspective group intervention developed by the investigators; the control group (n = 16) received no intervention. The effects of the intervention on the participants' hope, resilience and depression levels were evaluated as a pretest, post-test 1 (8th week) and post-test 2 (12th week) and were compared. The Chinese version of the State Hope Scale, the 25-item Resilience Scale, and the Taiwanese Depression Questionnaire were used in this study. RESULTS: On the eighth and twelfth weeks after the strengths-based perspective group intervention, we found significantly lower scores on the depression scale in the experimental group. In the eighth week, participants in the experimental group had significantly lower scores on the pathway of hope subscales than those in the control group. CONCLUSIONS: A strengths-based perspective support group intervention designed specifically for women who left a violent intimate partner relationship significantly reduced the participants' level of depressive symptoms and improved the pathway component of hope. RELEVANCE TO CLINICAL PRACTICE: This research highlights the importance of nurses not only focused on problems but also on the psychological strengths in practice of abused women survivors. PMID- 26818380 TI - Implementing evidence-based practices in an emergency department: contradictions exposed when prioritising a flow culture. AB - BACKGROUND: An emergency department is typically a place of high activity where practitioners care for unanticipated presentations, which yields a flow culture so that actions that secure available beds are prioritised by the practitioners. OBJECTIVES: How does the flow culture in an emergency department influence nurses' use of a research-based clinical guideline and a nutrition screening routine. METHODS: Ethnographic fieldwork was carried out over three months. The first author followed nurses, medical secretaries and doctors in the emergency department. Data were also collected by means of semi-structured interviews. An activity system analysis, as described in the Cultural Historical Activity Theory, was conducted to identify various contradictions that could exist between different parts of the activity system. RESULTS: The main contradiction identified was that guidelines and screening routines provided a flow stop. Four associated contradictions were identified: insufficient time to implement guidelines; guilty conscience due to perceived nonadherence to evidence-based practices; newcomers having different priorities; and conflicting views of what constituted being a professional. CONCLUSION: We found that research-supported guidelines and screening routines were not used if they were perceived to stop the patient flow, suggesting that the practice was not fully evidence based. PMID- 26818381 TI - Using a case-based animation on physiological compensatory mechanism to remediate nurses' misconceptions about changes in patient vital signs. PMID- 26818382 TI - High-Dose Adenosine for Treatment of Refractory Supraventricular Tachycardia in an Emergency Department of an Academic Medical Center: A Case Report and Literature Review. AB - BACKGROUND: Symptomatic tachycardia is a common admission diagnosis in the emergency department (ED). This can be a life-threatening condition and requires immediate attention. Supraventricular tachycardia (SVT) is commonly treated with adenosine, and successful treatment is limited to atrioventricular (AV) node dependent SVTs as adenosine causes a transient heart block. However, there are limited data available for instances when the recommended dosing regimen (6 mg, 12 mg, 12 mg) fails to terminate SVT. CASE REPORT: A 33-year old man was evaluated in the ED with an electrocardiogram revealing a regular narrow complex tachycardia with a heart rate of 180 beats/min and a rhythm consistent with SVT. He reported experiencing 3 days of fatigue, myalgias, palpitations, and dyspnea on exertion, but was otherwise hemodynamically stable. Attempts at chemical cardioversion with standard doses of adenosine (6 mg, 12 mg, and 12 mg) were given without success. After consultation with the cardiology service, additional doses of 24 mg and then 36 mg of adenosine were administered. The last dose of 36 mg produced sustained conversion and return to a normal sinus rhythm. The patient later underwent radiofrequency ablation of a left-sided orthodromic reciprocating accessory pathway. After 3 months of medical management, the patient had an implantable cardiac defibrillator placed for prevention of sudden cardiac death. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Each case of SVT demands immediate attention from an emergency physician. It is imperative that providers be aware of the limitations of adenosine and when it may be appropriate to deviate from standard dosing recommendations. This is in addition to collaborating with an expert in cardiac electrophysiology when initial management tactics are not successful. PMID- 26818383 TI - A Scoping Review: Communication Between Emergency Physicians and Patients in the Emergency Department. AB - BACKGROUND: Understanding the basic qualities of communication between emergency physicians and patients could improve communication in the emergency department. OBJECTIVE: The objectives of this scoping review are to map the literature about the gaps in communication between emergency physicians and patients in the emergency department and make recommendations for further research. METHODS: A scoping review of literature published since 1980 and written in English was undertaken using the following databases: Pubmed, Scopus, and SocINDEX. The articles were searched for using two-keyword combinations of the following keywords joined by "AND": "communication," "patient," "emergency physician," "emergency department/emergency room/accident," and "emergency room." Seventeen articles were included in the final review. RESULTS: Five research issues were covered by the 17 papers: patient-centered communication, information sharing, bad news delivery, shared decision making, and physicians' perspectives on communication. Emergency physicians have several communication characteristics: doctor-driven decision making, focusing on efficient information gathering, immature communication techniques, and obstacles to overcoming miscommunication. Patients also have several communication characteristics: active participation in medical encounters, expectation of physician as a reliable guide, understanding physicians' difficulties, and factors that contribute to understanding. CONCLUSIONS: Several conclusions about emergency department communication between patients and emergency physicians were drawn. Additional research is required to consider diverse patient needs in the emergency department. Furthermore, training programs for emergency physicians to improve the quality of communication should be developed and implemented in line with our research findings. PMID- 26818384 TI - An Unusual Case of Anaphylaxis after Blunt Abdominal Trauma. AB - BACKGROUND: Due to current human migratory patterns, emergency physicians in developed countries are facing emergent clinical presentations of neglected tropical diseases with increasing frequency. In those situations, the clinician's diagnosis is often delayed due to a lack of familiarity with the disease. CASE REPORT: We present the case of a 25-year-old Peruvian man who presented to the Emergency Department complaining of dyspnea and abdominal pain after upper abdominal trauma. His physical examination revealed mouth and eyelid edema in association with epigastric pain. An abdominal computed tomography scan revealed a liver hydatid cyst. Emergent surgical evacuation of the cyst was required to control the anaphylactic reaction. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Anaphylaxis in the setting of a complicated hydatid cyst is a life threatening disease. Critical care management and emergent surgical evacuation of the cyst are indicated. PMID- 26818385 TI - Value of CVP: an epidemiological or physiological question? PMID- 26818386 TI - Impaired dynamics of clot formation and hypofibrinolysis in severe sepsis are coexisting and strictly related. PMID- 26818390 TI - Carotid artery ultrasound for syncope. PMID- 26818387 TI - Gene expression profiling identifies candidate biomarkers for active and latent tuberculosis. AB - BACKGROUND: Tuberculosis (TB) is a serious infectious disease in that 90% of those latently infected with Mycobacterium tuberculosis present no symptoms, but possess a 10% lifetime chance of developing active TB. To prevent the spread of the disease, early diagnosis is crucial. However, current methods of detection require improvement in sensitivity, efficiency or specificity. In the present study, we conducted a microarray experiment, comparing the gene expression profiles in the peripheral blood mononuclear cells among individuals with active TB, latent infection, and healthy conditions in a Taiwanese population. RESULTS: Bioinformatics analysis revealed that most of the differentially expressed genes belonged to immune responses, inflammation pathways, and cell cycle control. Subsequent RT-PCR validation identified four differentially expressed genes, NEMF, ASUN, DHX29, and PTPRC, as potential biomarkers for the detection of active and latent TB infections. Receiver operating characteristic analysis showed that the expression level of PTPRC may discriminate active TB patients from healthy individuals, while ASUN could differentiate between the latent state of TB infection and healthy condidtion. In contrast, DHX29 may be used to identify latently infected individuals among active TB patients or healthy individuals. To test the concept of using these biomarkers as diagnostic support, we constructed classification models using these candidate biomarkers and found the Naive Bayes based model built with ASUN, DHX29, and PTPRC to yield the best performance. CONCLUSIONS: Our study demonstrated that gene expression profiles in the blood can be used to identify not only active TB patients, but also to differentiate latently infected patients from their healthy counterparts. Validation of the constructed computational model in a larger sample size would confirm the reliability of the biomarkers and facilitate the development of a cost-effective and sensitive molecular diagnostic platform for TB. PMID- 26818391 TI - School staff, parent and student perceptions of a Breakfast in the Classroom model during initial implementation. AB - OBJECTIVE: To understand perspectives of stakeholders during initial district wide implementation of a Breakfast in the Classroom (BIC) model of the School Breakfast Program. DESIGN: Qualitative data were collected from twenty-nine focus groups and twenty interviews with stakeholders in a school district early in the process of implementing a BIC model of the School Breakfast Program. SETTING: Ten elementary schools within a large, urban school district in the USA that served predominantly low-income, racial/ethnic minority students. SUBJECTS: Purposively selected stakeholders in elementary schools that had implemented BIC for 3-6 months: students (n 85), parents/guardians (n 86), classroom teachers (n 44), cafeteria managers (n 10) and principals (n 10). RESULTS: Four primary themes emerged, which were interpreted based on the Diffusion of Innovations model. School staff had changed their perceptions of both the relative disadvantages and costs related to time and effort of BIC over time; the majority of each stakeholder group expressed an appreciation for BIC; student breakfast consumption varied from day to day, related to compatibility of foods with child preferences; and stakeholders held mixed and various impressions of BIC's potential impacts. CONCLUSIONS: The study underscores the importance of engaging school staff and parents in discussions of BIC programming prior to its initiation to pre-emptively address concerns related to cost, relative disadvantages and compatibility with child preferences and school routines/workflow. Effectively communicating with stakeholders about positive impacts and nutritional value of the meals may improve support for BIC. These findings provide new information to policy makers, districts and practitioners that can be used to improve implementation efforts, model delivery and outcomes. PMID- 26818392 TI - Cross-plane heat transfer through single-layer carbon structures. AB - Graphene-based nano-structures have been recently proposed to function as additives to improve the conductivity of thermally sluggish phase change materials (PCMs). Based on the existing research studies, the improvement is dependent not only on the matrix material, but also on the geometry of the carbon structure. To gain more insight into the nano-scale thermal transport problem, we launched the current pilot research using water as the matrix material, to represent the hydroxyl-group-rich sugar alcohols as PCMs. We have found that the heat conduction across a graphene layer to water is much faster than the heat conduction to the graphene layer itself. Also, the high graphene-water thermal contact resistance fails to acknowledge the fast thermal kinetics of the low frequency phonons. In the investigation of the geometry effect, the cross-plane heat transfer coefficient is found to decrease with decreasing CNT diameter except CNT(9,9). PMID- 26818393 TI - Adsorptive Separation of 1-Butanol from Aqueous Solutions Using MFI- and FER-Type Zeolite Frameworks: A Monte Carlo Study. AB - Anaerobic fermentation can transform carbohydrates to yield a multicomponent mixture comprising mainly of acetone, 1-butanol, and ethanol (ABE) in a typical weight ratio of 3:6:1. Compared to ethanol, 1-butanol, the main product of ABE fermentation, offers significant advantages as a biofuel or a fuel additive. However, the toxicity of 1-butanol for cell cultures requires broth concentrations to be low in 1-butanol (~1-2 wt %). An energy-efficient recovery method that performs well even at low 1-butanol concentrations is therefore necessary to ensure economic feasibility of the ABE fermentation process. In this work, configurational-bias Monte Carlo simulations in the Gibbs ensemble are performed to probe the adsorption of 1-butanol/water solutions onto all-siliceous zeolites with the framework types MFI and FER. At low solution concentration, the selectivity and capacity for 1-butanol in MFI are larger than those in FER, while the opposite is true for concentrations at or above those of ABE broths. Structural analysis at various loadings sheds light on the different sorbate sorbate and sorbate-sorbent interactions that govern trends in adsorption in each zeolite. PMID- 26818395 TI - Hierachical Ni@Fe2O3 superparticles through epitaxial growth of gamma-Fe2O3 nanorods on in situ formed Ni nanoplates. AB - One endeavour of nanochemistry is the bottom-up synthesis of functional mesoscale structures from basic building blocks. We report a one-pot wet chemical synthesis of Ni@gamma-Fe2O3 superparticles containing Ni cores densely covered with highly oriented gamma-Fe2O3 (maghemite) nanorods (NRs) by controlled reduction/decomposition of nickel acetate (Ni(ac)2) and Fe(CO)5. Automated diffraction tomography (ADT) of the Ni-Fe2O3 interface in combination with Mossbauer spectroscopy showed that selective and oriented growth of the gamma Fe2O3 nanorods on the Ni core is facilitated through the formation of a Fe0.05Ni0.95 alloy and the appearance of superstructure features that may reduce strain at the Ni-Fe2O3 interface. The common orientation of the maghemite nanorods on the Ni core of the superparticles leads to a greatly enhanced magnetization. After functionalization with a catechol-functional polyethylene glycol (C-PEG) ligand the Ni@gamma-Fe2O3 superparticles were dispersible in water. PMID- 26818396 TI - [Multiseptate gallbladder as a casual finding. What to do?] PMID- 26818394 TI - Interictal spikes during sleep are an early defect in the Tg2576 mouse model of beta-amyloid neuropathology. AB - It has been suggested that neuronal hyperexcitability contributes to Alzheimer's disease (AD), so we asked how hyperexcitability develops in a common mouse model of beta-amyloid neuropathology - Tg2576 mice. Using video-EEG recordings, we found synchronized, large amplitude potentials resembling interictal spikes (IIS) in epilepsy at just 5 weeks of age, long before memory impairments or beta amyloid deposition. Seizures were not detected, but they did occur later in life, suggesting that IIS are possibly the earliest stage of hyperexcitability. Interestingly, IIS primarily occurred during rapid-eye movement (REM) sleep, which is notable because REM is associated with increased cholinergic tone and cholinergic impairments are implicated in AD. Although previous studies suggest that cholinergic antagonists would worsen pathophysiology, the muscarinic antagonist atropine reduced IIS frequency. In addition, we found IIS occurred in APP51 mice which overexpress wild type (WT)-APP, although not as uniformly or as early in life as Tg2576 mice. Taken together with results from prior studies, the data suggest that surprising and multiple mechanisms contribute to hyperexcitability. The data also suggest that IIS may be a biomarker for early detection of AD. PMID- 26818397 TI - [Primary lymphedema due to Milroy disease]. PMID- 26818398 TI - Long-term toxicity of naturally occurring asbestos in male Fischer 344 rats. AB - Naturally occurring asbestos (NOA) fibers are found in geologic deposits that may be disturbed by mining, earthworks, or natural processes, resulting in adverse health risks to exposed individuals. The toxicities of Libby amphibole and NOA samples including Sumas Mountain chrysotile (SM), El Dorado tremolite (ED), and Ontario ferroactinolite cleavage fragments (ON) were compared in male Fischer 344 (F344) rats 15 mo after exposure. Rat-respirable fractions of LA and SM displayed greater mean lengths and aspect ratios than ED and ON. After a single intratracheal (IT) instillation (0.5 or 1.5 mg/rat), persistent changes in ventilatory parameters and a significant increase in lung resistance at baseline and after methacholine aerosol dosing were found only in rats exposed to 1.5 mg SM. High-dose ED significantly elevated bronchoalveolar lavage lactate dehydrogenase (LDH) activity and protein levels, while high-dose SM increased gamma-glutamyl transferase and LDH activities. A moderate degree of lung interstitial fibrosis after exposure to 1.5 mg SM persisted 15 mo after exposure, unchanged from previous findings at 3 mo. LA induced mild fibrosis, while ED and ON produced minimal and no apparent fibrosis, respectively. Bronchioloalveolar carcinoma was observed 15 mo after exposure to LA or ED. Data demonstrated that SM, given by bolus IT dosing on an equivalent mass basis, induced greater pulmonary function deficits, airway hyperresponsiveness, and interstitial fibrosis than other NOA, although unlike LA and ED, no apparent evidence for carcinogenicity was found. All NOA samples except ON cleavage fragments produced some degree of long-term toxicity. PMID- 26818399 TI - Haploinsufficiency of the STX1B gene is associated with myoclonic astatic epilepsy. AB - We describe an 18-year-old male patient with myoclonic astatic epilepsy (MAE), moderate to severe intellectual disability, behavioural problems, several dysmorphisms and a 1.2-Mb de novo deletion on chromosome 16p11.2. This deletion results in haploinsufficiency of STX1B and other genes. Recently, variants in the STX1B gene have been associated with a wide spectrum of fever-related epilepsies ranging from single febrile seizures to severe epileptic encephalopathies. Two previously reported patients with a STX1B missense variant or deletion were diagnosed with MAE. Our observation of a STX1B deletion in a third patient with MAE therefore supports that STX1B gene variants or deletions can be involved in the aetiology of MAE. Furthermore, STX1B encodes for syntaxin-1B, of which interaction with the protein encoded by the STXBP1 gene is essential for the regulation of the synaptic transmission of neurotransmitters. STXBP1 gene variants have been identified in patients with many different types of epilepsy, including Dravet syndrome and epileptic encephalopathies, suggesting STX1B plays a similar role. We recommend that analysis of STX1B should be considered in the diagnostic work-up of individuals with MAE. PMID- 26818400 TI - Evaluation of a multidisciplinary epilepsy transition clinic for adolescents. AB - INTRODUCTION: The main goal of the transition clinic is to explore and optimize medical issues during transition from adolescence to adulthood, and to ease the transition into adult care. However, only limited data on the process and outcomes of transitional care in clinical practice are available. OBJECTIVE: To describe the process and outcomes of an Epilepsy Transition Clinic in a tertiary referral center in The Netherlands. METHODS: Data were collected from patients with epilepsy (aged 15-25 years), who visited the transition clinic between March 2012 and September 2014. RESULTS: The Epilepsy Transition Clinic is staffed with a multidisciplinary team including a neurologist/epileptologist, clinical neuropsychologist, a social worker and an educationalist/occupational counselor, all with knowledge of paediatric and adult medical and developmental issues. In total, 117 patients with epilepsy were included in the analysis. After consultation, 89 patients received a diagnostic work-up (76.1%), change in AED prescription (n = 64, 54.7%), or consultation/tailored advice (n = 73, 62.4%). In fourteen patients (12.0%) the epilepsy diagnosis was changed. Nineteen patients (16.2%) had complete epilepsy remission for over one year. Forty-three patients (36.8%) were referred to adult care. CONCLUSION: This study describes a multidisciplinary epilepsy transition clinic staffed by a neurologist/epileptologist, neuropsychologist, a social worker and an educationalist/occupational counselor. Diagnostic work-up and evaluation of psychosocial and educational/vocational status during adolescence are strongly recommended. PMID- 26818401 TI - Negative Tuberculin Skin Test and Prediction of Reversion of QuantiFERON Interferon Gamma Release Assay in US Healthcare Workers. AB - QuantiFERON tuberculosis tests (QFT) reverted in (612) 77% of 1,094 low-risk healthcare workers (HCW) testing less than 1.16 IU/mL. Of HCW testing greater than 1.1 IU/mL, 33 (59%) of 56 with negative tuberculin skin tests (TST) reverted vs 8 (6%) of 125 with positive TSTs. Retesting low-risk QFT-positive and TST negative HCW is prudent. PMID- 26818402 TI - The longitudinal association of cognitive appraisals and coping strategies with physical functioning in older adults with joint pain and comorbidity: a cohort study. AB - BACKGROUND: Substantial variation exists in physical functioning (PF) among patients with comparable pain severity, which may be partly explained by underlying psychological processes, like cognitive appraisal of pain and coping with pain. It remains unclear to what extent such determinants contribute to changes in PF over time, especially in older populations. Therefore, we examined longitudinal associations of cognitive appraisals and coping strategies with PF, in older adults with joint pain and comorbidity. METHODS: A prospective cohort study among 407 older adults with joint pain and comorbidity provided data over 18 months, with 6 month time-intervals. We measured PF (RAND-36), five cognitive appraisals (consequences, concerns, emotional representations, self-efficacy, catastrophizing), four coping strategies (ignoring pain, positive self-statement, increasing activity levels, activity avoidance) and three time-dependent covariates; pain intensity, anxiety and depressive symptoms. Longitudinal associations were analyzed with Generalized Estimated Equations (GEE), by testing auto-regressive models, adjusted for covariates. RESULTS: More negative thoughts about consequences of pain (beta = -0.54, 95% CI = -1.02; -0.06), more catastrophizing (beta = -0.67, 95% CI = -1.26; -0.07) and more activity avoidance (beta = -0.32, 95% CI = -0.57; -0.08) were significantly associated with subsequent deterioration in PF, whereas higher perceived self-efficacy (beta = 0.22, 95% CI = 0.12; 0.31) was associated with subsequent improvement in PF. Neither concerns, emotional representations, ignoring pain, positive self statement nor increasing activity levels were longitudinally related to PF. CONCLUSIONS: More negative thoughts about consequences of pain, more catastrophizing and more activity avoidance contributed to deteriorated PF, whereas higher perceived self-efficacy contributed to improved PF. This knowledge may contribute to future management of functional limitations in older adults with joint pain and comorbidity. PMID- 26818405 TI - Risk of symptomatic venous thromboembolism following emergency appendicectomy in adults. AB - BACKGROUND: Appendicectomy is the commonest intra-abdominal emergency surgical procedure, and little is known regarding the magnitude and timing of the risk of venous thromboembolism (VTE) after surgery. This study aimed to determine absolute and relative rates of symptomatic VTE following emergency appendicectomy. METHODS: A cohort study was undertaken using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data of patients who had undergone emergency appendicectomy from 2001 to 2011. Crude rates and adjusted incidence rate ratios (IRRs) for VTE were calculated using Poisson regression, compared with baseline risk in the year before appendicectomy. RESULTS: A total of 13 441 patients were identified, of whom 56 (0.4 per cent) had a VTE in the first year after surgery. The absolute rate of VTE was highest during the in-hospital period, with a rate of 91.29 per 1000 person-years, which was greatest in those with a length of stay of 7 days or more (267.12 per 1000 person-years). This risk remained high after discharge, with a 19.1- and 6.6-fold increased risk of VTE in the first and second months respectively after discharge, compared with the year before appendicectomy (adjusted IRR: month 1, 19.09 (95 per cent c.i. 9.56 to 38.12); month 2, 6.56 (2.62 to 16.44)). CONCLUSION: The risk of symptomatic VTE following appendicectomy is relatively high during the in-hospital admission and remains increased after discharge. Trials of extended thromboprophylaxis are warranted in patients at particularly high risk. PMID- 26818403 TI - The effectiveness and safety of treatments used for acute diarrhea and acute gastroenteritis in children: protocol for a systematic review and network meta analysis. AB - BACKGROUND: Acute diarrhea and acute gastroenteritis (AD/AGE) are common among children in low- and middle-income countries (LMIC) and high-income countries (HIC). Supportive therapy including maintaining feeding, prevention of dehydration, and use of oral rehydration solution (ORS), is the mainstay of treatment in all children. Several additional treatments aiming to reduce the episode duration have been compared to placebo, but the differences in effectiveness among them are unknown. METHODS AND ANALYSIS: We will conduct a systematic review of all randomized controlled trials evaluating the use of zinc, vitamin A, probiotics, prebiotics, synbiotics, racecadotril, smectite, and fermented and lactose-free milk/formula for AD/AGE treatment in children. The primary outcomes are diarrhea duration and mortality. Secondary outcomes are diarrhea lasting 3 or 7 days, stool frequency, treatment failure, hospitalizations, and adverse events. We will search MEDLINE, Ovid EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), and LILACS through Ovid, as well as grey literature resources. Two reviewers will independently screen titles and abstracts, review full texts, extract information, and assess the risk of bias (ROB) and the confidence in the estimate (with the grading of recommendations, assessment, development, and evaluation [GRADE] approach). Results will be summarized narratively and statistically. Subgroup analysis according to HIC vs. LMIC, age, nutrition status, and ROB is planned. We will perform a Bayesian network meta-analysis to combine the pooled direct and indirect treatment effect estimates for each outcome, if adequate data is available. DISCUSSION: This is the first systematic review and network meta analysis that aims to determine the relative effectiveness of pharmacological and nutritional treatments for reducing the duration of AD/AGE in children. The results will help to reduce the uncertainty of the effectiveness of the interventions, find knowledge gaps, and/or encourage further research for other therapeutic options. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42015023778. PMID- 26818406 TI - Interchangeability, Safety and Efficacy of Modified-Release Drug Formulations in the USA: The Case of Opioid and Other Nervous System Drugs. AB - BACKGROUND AND OBJECTIVES: Modified-release drugs may provide clinical advantages compared to immediate-release forms and improve convenience to the patient and health outcomes. Concerns have been raised regarding interchangeability, efficacy, and safety of modified-release formulations. This study analyses all US Food and Drug Administration (FDA)-approved modified-release formulations and market trends, and illustrates how bioequivalence and safety of generic modified release products compare to their respective brand name drugs and other generic drugs with different formulation design characteristics. This study also examines major concerns related to modified-release formulations: safety of opioids and bioequivalence of generic bupropion and methylphenidate. METHODS: Study data were derived from the FDA electronic versions of the FDA's Orange Book (OB) and the FDA safety communications web page. Medicare Part D utilization and expenditures data were extracted from the Centers for Medicare and Medicaid. RESULTS: In May 2015, 276 (11.9 %) of the 2325 active ingredients and fixed-dose combinations listed in the FDA's Orange Book had at least one modified-release form approved by the FDA. The number of approvals increased over time; 52.5 % of modified releases were approved in the period 2000-May 2015. The FDA required a risk evaluation and mitigation strategy (REMS) to ensure that the benefits of extended release opioids outweighed its risks of overdose and abuse. The REMS involved 16 new drug applications and 25 abbreviated new drug applications. CONCLUSIONS: The FDA addressed interchangeability problems with generic modified-release alternatives of bupropion and methylphenidate including lack of bioequivalence, reduced efficacy, and increased incidence of adverse events. Systematic post marketing surveillance studies are needed to assess differences in safety, interchangeability, and efficacy of drugs with modified- and immediate-release formulations. PMID- 26818407 TI - Home-administered pre-surgical psychological intervention for knee osteoarthritis (HAPPiKNEES): study protocol for a randomised controlled trial. AB - BACKGROUND: Knee replacement surgery reduces pain for many people with osteoarthritis (OA). However, surgical outcomes are partly dependent on patients' moods, and those with depression or anxiety have worse outcomes. Approximately one-third of people with OA have mood problems. Cognitive behavioural therapy (CBT), a psychological therapy, is recommended by the National Institute for Health and Care Excellence for improving mood. However, evidence for the effectiveness of CBT before knee surgery in improving pain, mood, and quality of life following this surgery for people with knee OA is lacking. METHODS/DESIGN: This is a multi-centre, mixed-methods feasibility randomised controlled trial to compare treatment as usual (TAU) plus a brief CBT-based intervention with a TAU only control, for people with knee OA. We will recruit 50 patients with knee OA, listed for knee replacement surgery, with high levels of distress (assessed using a mood questionnaire), and who consent to take part. Participants will be randomly allocated to receive TAU plus intervention or TAU. Up to 10 sessions of CBT will be offered on an individual basis by a psychologist. The assessments and interventions will be completed before surgery. Repeat assessments at 4 and 6 months after randomisation will be sent and received by post. Two patient partners will conduct feedback interviews with some participants to assess what aspects of the intervention were helpful or unhelpful, the acceptability of randomisation, the experience of being in a control group, and the appropriateness of the measures used. Interviews will be audio-recorded, transcribed, and analysed using the framework approach. We will examine the feasibility and acceptability of patient-partners conducting the interviews by also interviewing the patient-partners. DISCUSSION: Findings from this study will be used to design a definitive study that will examine the clinical and cost effectiveness of the CBT intervention in improving patient outcomes following knee surgery. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80222865; Date: 19 June 2014. PMID- 26818408 TI - Bactericidal activity of green tea extracts: the importance of catechin containing nano particles. AB - When we drink green tea infusion, we believe we are drinking the extract of the green tea leaves. While practically each tea bag infused in 300 mL water contains about 50 mg of suspended green tea leaf particles. What is the role of these particles in the green tea effect is the objective of this study. These particles (three different size ranges) were isolated via varying speed centrifugation and their respective inputs evaluated. Live oral bacterial samples from human volunteers have been screened against green tea extracts and macro, micro and nano sized green tea particles. The results showed that the presence/absence of the macro and mico sized tea particles in the green tea extract did not contribute much. However, the nano sized particles were characterized to be nature's nano stores of the bioactive catechins. Eradication of these nano tea particles resulted in decrease in the bactericidal property of the green tea extracts. This is a curtain raiser investigation, busting the nano as well as green tea leaf particle contribution in green tea extracts. PMID- 26818409 TI - Association Between Indoor Tanning and Melanoma in Younger Men and Women. AB - IMPORTANCE: In the United States and Minnesota, melanoma incidence is rising more steeply among women than men younger than 50 years. To our knowledge, no study has examined age- and sex-specific associations between indoor tanning and melanoma to determine if these trends could be due to greater indoor tanning use among younger women. OBJECTIVE: To examine associations between indoor tanning and melanoma among men and women younger than 50 years. DESIGN, SETTING, AND PARTICIPANTS: Population-based case-control study conducted in Minnesota of 681 patients (465 [68.3%] women) diagnosed as having melanoma between 2004 and 2007, and 654 controls (446 [68.2%] women), ages 25 to 49 years. EXPOSURE: Indoor tanning, defined as any use, first age of use, and total sessions. MAIN OUTCOMES AND MEASURES: Crude and adjusted odds ratios (ORs) and 95% CIs were calculated for melanoma in relation to indoor tanning exposure for men and women by diagnosis or reference age (<30, 30-39, 40-49 years). Sex-specific associations for indoor tanning and melanoma by anatomic site were examined. RESULTS: Compared with women aged 40 to 49 years, women younger than 40 years initiated indoor tanning at a younger age (16 vs 25 years, P < .001) and reported more frequent indoor tanning (median number of sessions, 100 vs 40, P < .001). Women younger than 30 years were 6 times more likely to be in the case than the control group if they tanned indoors (crude OR, 6.0; 95% CI, 1.3-28.5). Odds ratios were also significantly elevated among women, ages 30 to 49 years (adjusted OR, 3.5; 95% CI, 1.2-9.7 for women 30-39 years; adjusted OR, 2.3; 95% CI, 1.4-3.6 for women 40 49 years); a dose response was observed among women regardless of age. Among men, results by age were inconsistent. The strongest OR for indoor tanning by anatomic site was for melanomas arising on the trunk of women (adjusted OR, 3.7; 95% CI, 1.9-7.2). CONCLUSIONS AND RELEVANCE: Indoor tanning is a likely factor for the steeper increase in melanoma rates in the United States among younger women compared with men, given the timing of when women initiated indoor tanning relative to diagnosis. The melanoma epidemic can be expected to continue unless indoor tanning is restricted and reduced. PMID- 26818410 TI - Evaluation of prehypertension and masked hypertension rate among clinically normotensive patients. AB - BACKGROUND: The present cross-sectional study was aimed to identify pre hypertension and masked hypertension rate in clinically normotensive adults in relation to socio-demographic, clinical and laboratory parameters. METHODS: A total of 161 clinically normotensive adults with office blood pressure (OBP) <140/90 mmHg without medication were included in this single-center cross sectional study. OBP, home BP (HBP) recordings and ambulatory BP monitoring (ABPM) were used to identify rates of true normotensives, true pre-hypertensives and masked hypertensives. Data on sociodemographic and clinical characteristics were collected in each subject and evaluated with respect to true normotensive vs. pre-hypertensive patients with masked hypertension or true pre-hypertensive. Target organ damage (TOD) was evaluated in masked hypertensives based on laboratory investigation. RESULTS: Masked hypertension was identified in 8.7% of clinically normotensives. Alcohol consumption was significantly more common in masked hypertension than in true pre-hypertension (28.6 vs. 0.0%, p = 0.020) with risk ratio of 2.7 (95% CI 1.7-4.4). Patients with true pre-hypertension and masked hypertension had significantly higher values for body mass index, waist circumference, systolic and diastolic OBP and HBP (p < 0.05 for each) compared to true normotensive subjects. ABPM revealed significantly higher values for day time and night-time systolic and diastolic BP (p = 0.002 for night-time diastolic BP, p < 0.001 for others) in masked hypertension than true pre-hypertension. CONCLUSIONS: Given that the associations of pre-hypertension with TOD might be attributable to the high prevalence of insidious presentation of masked hypertension among pre-hypertensive individuals, ABPM seems helpful in early identification and management of masked hypertension in the pre-hypertensive population. PMID- 26818411 TI - Two clinical cases of renal syndrome caused by Dobrava/Saaremaa hantaviruses imported to the Netherlands from Poland and Belarus, 2012-2014. AB - We report the rare event of two imported cases in the Netherlands presenting with renal syndrome caused by Dobrava (DOBV)/Saaremaa (SAAV) hantaviruses. DOBV/SAAV hantaviruses are not circulating in the Netherlands and their clinical manifestation is typically more severe than that of the endemic Puumala virus (PUUV). This report aims to increase awareness among healthcare professionals and diagnostic laboratories to consider different hantaviruses as a cause of renal failure. PMID- 26818413 TI - Acceptance- and mindfulness-based interventions for the treatment of chronic pain: a meta-analytic review. AB - The number of acceptance- and mindfulness-based interventions for chronic pain, such as acceptance and commitment therapy (ACT), mindfulness-based stress reduction (MBSR), and mindfulness-based cognitive therapy (MBCT), increased in recent years. Therefore an update is warranted of our former systematic review and meta-analysis of studies that reported effects on the mental and physical health of chronic pain patients. Pubmed, EMBASE, PsycInfo and Cochrane were searched for eligible studies. Current meta-analysis only included randomized controlled trials (RCTs). Studies were rated for quality. Mean quality did not improve in recent years. Pooled standardized mean differences using the random effect model were calculated to represent the average intervention effect and, to perform subgroup analyses. Outcome measures were pain intensity, depression, anxiety, pain interference, disability and quality of life. Included were twenty five RCTs totaling 1285 patients with chronic pain, in which we compared acceptance- and mindfulness-based interventions to the waitlist, (medical) treatment-as-usual, and education or support control groups. Effect sizes ranged from small (on all outcome measures except anxiety and pain interference) to moderate (on anxiety and pain interference) at post-treatment and from small (on pain intensity and disability) to large (on pain interference) at follow-up. ACT showed significantly higher effects on depression and anxiety than MBSR and MBCT. Studies' quality, attrition rate, type of pain and control group, did not moderate the effects of acceptance- and mindfulness-based interventions. Current acceptance- and mindfulness-based interventions, while not superior to traditional cognitive behavioral treatments, can be good alternatives. PMID- 26818412 TI - White matter alterations in individuals experiencing attenuated positive psychotic symptoms. AB - AIM: Diffusion tensor imaging (DTI) studies suggest that reduced fractional anisotropy (FA) in the inferior longitudinal fasciculus (ILF) and superior longitudinal fasciculus (SLF) occurs among schizophrenia patients and those at risk for psychosis. Nevertheless, there is a dearth of knowledge investigating white matter fibre pathways in non-help-seeking individuals who endorse attenuated positive psychotic symptoms (APPS) across a range of mental disorders. The aim of the current study was to determine if alterations in ILF and SLF microstructures were specific to distressing APPS related to risk for psychosis or to APPS symptoms occurring in multiple mental disorders, which would suggest a shared phenotype among disorders. METHOD: Twenty-six non-help-seeking young adults were administered the Prodromal Questionnaire. DTI was conducted on participants (n = 13) who endorsed eight or more distressing APPS (D-APPS, a potentially clinically relevant group) and those who endorsed three or fewer distressing APPS (low-APPS; n = 13). Semistructured interviews were administered to determine diagnoses, as well as clinical risk for psychosis status. RESULTS: Results indicated that the D-APPS group exhibited decreased FA in the left ILF compared with the low-APPS group, even after removing four D-APPS participants who were considered at risk for psychosis. CONCLUSION: Findings suggest that white matter microstructure is altered in individuals experiencing APPS across a range of disorders, independent of clinical high risk for psychosis status. Reduced FA in the left ILF may not be specific to psychosis risk, but rather for APPS that occur in a number of mental disorders. PMID- 26818414 TI - Patients who are not driving 6 weeks after transient ischaemic attack have higher levels of anxiety. PMID- 26818415 TI - Should we ban boxing? PMID- 26818416 TI - Violet and blue light-induced green fluorescence emissions from dental caries. AB - BACKGROUND: The objective of this laboratory study was to compare violet and visible blue LED light-elicited green fluorescence emissions from enamel and dentine in healthy or carious states. METHODS: Microscopic digital photography was undertaken using violet and blue LED illumination (405 nm and 455 nm wavelengths) of tooth surfaces, which were photographed through a custom-made stack of green compensating filters which removed the excitation light and allowed green fluorescence emissions to pass. Green channel pixel data were analysed. RESULTS: Dry sound enamel and sound root surfaces showed strong green fluorescence when excited by violet or blue lights. Regions of cavitated dental caries gave lower green fluorescence, and this was similar whether the dentine in the lesions was the same colour as normal dentine or was darkly coloured. The presence of saliva on the surface did not significantly change the green fluorescence, while the presence of blood diluted in saliva depressed green fluorescence. CONCLUSIONS: Using violet or blue illumination in combination with green compensating filters could potentially aid in the assessment of areas of mineral loss. PMID- 26818417 TI - Evaluating Study Withdrawal Among Biologics and Immunomodulators in Treating Ulcerative Colitis: A Meta-analysis of Controlled Clinical Trials. AB - BACKGROUND: We conducted a systematic review and meta-analysis to evaluate the efficacy and adverse event (AE)-associated tolerability of treatment with immunomodulators and biologics in ulcerative colitis clinical trials. METHODS: We performed a literature search of PubMed and the Cochrane databases to identify randomized placebo-controlled trials of immunomodulators and biologics. Tolerability was defined through study withdrawal due to AEs and efficacy through clinical response in induction trials and clinical remission in maintenance trials. We performed meta-analyses using a random-effects model to determine relative risks (RRs) of efficacy and study withdrawal. Number needed to treat (NNT) and number needed to stop (NNS) were determined. The ratio of NNS/NNT was calculated, with a higher ratio indicating a greater number of patients in remission for every AE study discontinuation. RESULTS: We examined 13 single agent trials representing biologics (infliximab, adalimumab, golimumab, and vedolizumab) and immunomodulators (tacrolimus and azathioprine). Induction therapy did not result in excess study withdrawal with immunomodulators (RR = 0.9, 95% CI 0.1-12.0) or biologics (RR = 0.7, 95% CI 0.3-1.8), therefore the NNS/NNT ratio could not be assessed because of high tolerability. Maintenance immunomodulator therapy resulted in a NNS of 14 (RR = 2.8, 95% CI 0.7-10.5) and NNS/NNT ratio of 2.4 in 2 trials. Biologics did not result in excess study withdrawal in maintenance (RR = 0.7, 95% CI 0.3-1.7) or combined induction-and maintenance (RR = 0.6, 95% CI 0.4-1.0) trials. CONCLUSIONS: Biologics were not associated with a higher RR of study withdrawal due to AE than placebo. There were insufficient data to compare these results with immunomodulators. PMID- 26818418 TI - Disease Activity Does Not Explain It All: How Internalizing Symptoms and Caregiver Depressive Symptoms Relate to Health-related Quality of Life Among Youth with Inflammatory Bowel Disease. AB - BACKGROUND: Health-related quality of life (HRQoL) is a multidimensional constructinfluenced by disease, individual, and environmental factors. Greater disease activity (DA) predicts poorer HRQoL, but disease status alone does not fully account for individual variability in HRQoL. This investigation tested the role of patient and caregiver internalizing symptoms in explaining the relationship between DA and patient HRQoL. METHODS: Participants included 83 subjects aged 11 to 18 diagnosed with inflammatory bowel disease and their caregiver. Patients reported on their HRQoL. Caregivers rated their own depressive symptoms and patients' internalizing symptoms (depression, anxiety, and somatization). Physicians rated DA. RESULTS: Greater DA was positively associated with subjects' internalizing symptoms and negatively associated with HRQoL. Mediation analyses found support for significant indirect effects on the relationship between DA and HRQoL through the subjects' internalizing symptoms, through their internalizing symptoms and caregivers' depressive symptoms, sequentially. CONCLUSIONS: Greater DA independently relates to poorer HRQoL. In addition, DA relates to greater child internalizing problems which in turn relate to higher levels of caregiver depressive symptoms and poorer HRQoL. Providers may consider a family-based approach to screen for internalizing problems, especially in patients with active disease, because caregiver and child mood symptoms may partially explain worsening child HRQoL. PMID- 26818419 TI - Anti-TNF Therapy Within 2 Years of Crohn's Disease Diagnosis Improves Patient Outcomes: A Retrospective Cohort Study. AB - BACKGROUND: Although biological agents targeting tumor necrosis factor (TNF) alpha are effective in the management of Crohn's disease (CD), use of anti-TNF agents is often delayed until after failure of other treatment modalities, resulting in potentially long delays between diagnosis and initiation of infliximab or adalimumab. We aim to determine if early treatment with anti-TNF agents reduces the rate of surgical resection and clinical secondary loss of response in CD patients. METHODS: A retrospective cohort study was conducted evaluating CD outpatients who were primary responders to anti-TNF therapy, on a maintenance regimen with infliximab or adalimumab from 2003 to 2014. Patients were stratified by time to first dose of anti-TNF therapy; early initiation was defined as starting anti-TNF therapy within 2 years of diagnosis. The primary outcome was occurrence of surgical resection or clinical secondary loss of response requiring dose escalation. Kaplan-Meier analysis was used to assess time to the primary outcomes. RESULTS: One hundred ninety CD patients met inclusion criteria (100 infliximab, 90 adalimumab). Median follow-up duration was 154.4 weeks (inter quartile range, 106.4-227.8). Fifty-three patients (27.9%) had early initiation of anti-TNF therapy. Fewer patients in the early initiation group required surgery (5.7% versus 30.7%, P < 0.001) or experienced clinical secondary loss of response (45.3% versus 67.2%, P = 0.006). In Kaplan-Meier analysis, early initiation of anti-TNF therapy prolonged time to surgery (P = 0.001) and secondary loss of response (P = 0.006). CONCLUSIONS: In CD patients, early initiation of infliximab or adalimumab within the first 2 years of diagnosis reduces the rate of surgery and secondary loss of response requiring dose escalation. PMID- 26818420 TI - Comparison of Fecal Inflammatory Markers in Crohn's Disease. AB - BACKGROUND: Fecal biomarkers are used increasingly to monitor Crohn's disease (CD). However, the relative accuracy of different markers in identifying inflammation has been poorly evaluated. We evaluated fecal calprotectin (FC), lactoferrin (FL), and S100A12 (FS) using endoscopic validation in a prospective study of the progression of CD after intestinal resection. METHODS: Data were collected from 135 participants in a prospective, randomized, controlled trial aimed at preventing postoperative CD recurrence. Three hundred nineteen stool samples were tested for FC, FL, and FS preoperatively and 6, 12, and 18 months after resection. Colonoscopy was performed at 6 and/or 18 months. Endoscopic recurrence was assessed blindly using the Rutgeerts score. C-reactive protein (CRP) and Crohn's Disease Activity Index (CDAI) were assessed. RESULTS: FC, FL, and FS concentrations were elevated preoperatively (median: 1347, 40.9, and 8.4 MUg/g, respectively). At 6 months postoperatively, marker concentrations decreased (166, 3.0, 0.9 MUg/g) and were higher in recurrent disease than remission (275 versus 72 MUg/g, P < 0.001; 5.7 versus 1.6 MUg/g, P = 0.007; 2.0 versus 0.8 MUg/g, P = 0.188). FC > 135 MUg/g, FL > 3.4 MUg/g, and FS > 10.5 MUg/g indicated endoscopic recurrence (score >= i2) with a sensitivity, specificity, and negative predictive value (NPV) of 0.87, 0.66, and 91%; 0.70, 0.68, and 81%; 0.91, 0.12, and 71%, respectively. FC and FL correlated significantly with the presence and severity of endoscopic recurrence, whereas FS, CRP and CDAI did not. CONCLUSIONS: FC was the optimal fecal marker for monitoring disease activity in postoperative CD and was superior to CRP and CDAI. FL offered modest sensitivity for detecting recurrent disease, whereas S100A12 was sensitive but had low specificity and NPV. PMID- 26818421 TI - The Relevance of Vitamin D and Antinuclear Antibodies in Patients with Inflammatory Bowel Disease Under Anti-TNF Treatment: A Prospective Study. AB - BACKGROUND: The importance of vitamin D in inflammatory bowel disease (IBD) has been analyzed in former studies, namely concerning the severity of the disease and the efficacy of anti-tumor necrosis factor (TNF) medications. In several inflammatory conditions, biologics have been associated with an autoimmune response with formation of antinuclear antibodies (ANA). In addition, an inverse relationship between vitamin D levels and ANA has been documented. We aimed to evaluate the clinical importance of the link between vitamin D, ANA, and anti-TNF in patients with IBD. METHODS: Prospective study including patients with IBD with indication to start anti-TNF, between 2009 and 2014. Deficiency and extreme deficiency of vitamin D were defined as levels of 25-hydroxyvitamin D below 20 and 4 ng/mL, respectively. ANA titers were considered positive if higher or equal to 1/100. RESULTS: Among 68 patients (56 with Crohn's Disease, 12 with ulcerative colitis), vitamin D deficiency was detected in 93%. Pretreatment positivity for ANA was related to higher failure rates of anti-TNF treatment (P = 0.008). Pretreatment positivity for ANA and extreme vitamin D deficiency were significant risk factors for adverse events associated with anti-TNF therapy. A significant link was found between extreme deficiency of vitamin D and the presence of ANA. CONCLUSIONS: Our study highlights the association between vitamin D deficiency and pretreatment positivity for ANA with the risk for anti-TNF failure and adverse events, and the inverse relationship between vitamin D levels and ANA. Due to the high prevalence of vitamin D deficiency in IBD and the immune-mediated nature of the disease, these elements should be evaluated before starting biologics. PMID- 26818422 TI - Anemia of Chronic Disease and Iron Deficiency Anemia in Inflammatory Bowel Diseases: Pathophysiology, Diagnosis, and Treatment. AB - Anemia coexists with inflammatory bowel disease (IBD) in up to two-thirds of patients, significantly impairing quality of life. The most common types of anemia in patients with IBD are iron deficiency anemia and anemia of chronic disease, which often overlap. In most cases, available laboratory tests allow successful diagnosis of iron deficiency, where difficulties appear, recently established indices such as soluble transferrin-ferritin ratio or percentage of hypochromic red cells are used. In this review, we discuss the management of the most common types of anemia in respect of the latest available data. Thus, we provide the mechanisms underlying pathophysiology of these entities; furthermore, we discuss the role of hepcidin in developing anemia in IBD. Next, we present the treatment options for each type of anemia and highlight the importance of individual choice of action. We also focus on newly developed intravenous iron preparations and novel, promising drug candidates targeting hepcidin. Concurrently, we talk about difficulties in differentiating between the true and functional iron deficiency, and discuss tools facilitating the process. Finally, we emphasize the importance of proper diagnosis and treatment of anemia in IBD. We conclude that management of anemia in patients with IBD is tricky, and appropriate screening of patients regarding anemia is substantial. PMID- 26818424 TI - IL-6 Mediates the Intestinal Microvascular Thrombosis Associated with Experimental Colitis. AB - Inflammatory bowel diseases are associated with increased risk for thrombus formation both within the inflamed bowel and at distant sites. Although the increased propensity for distant organ thrombus development has been recapitulated in animal models of colitis and linked to interleukin-6 (IL-6), it remains unclear whether experimental colitis results in accelerated thrombus development within the inflamed bowel and whether IL-6 contributes to a local thrombogenic response. These issues related to thrombus formation within the inflamed bowel were addressed in mice with dextran sodium sulfate-induced colitis. Wild-type (WT) mice, IL-6 deficient (IL-6(-/-)) mice, and bone marrow chimeras (WT->WT and IL-6(-/-)->WT) were used. The effects of treatment with either an IL-6-blocking, IL-6Ralpha-blocking or gp130-blocking antibody were also evaluated. Disease activity index and colonic weight-to-length ratio (W/L) were used to monitor the development of colitis. Intravital videomicroscopy was used to study thrombus development (induced with the light/dye method) in mucosal vessels of the ascending colon. Thrombus development was significantly enhanced in WT colitic mice. Neither genetic deficiency nor immunoblockade of IL-6 significantly altered the disease activity index and W/L responses to dextran sodium sulfate treatment. However, colitis-induced thrombogenesis was attenuated in IL-6(-/-) mice and in WT mice treated with either the IL-6-blocking, IL 6Ralpha-blocking or gp130-blocking antibody. IL-6(-/-)->WT, but not WT->WT chimeras, exhibited a blunted thrombosis response to dextran sodium sulfate. These results indicate that experimental colitis is associated with accelerated thrombus development within the inflamed colon and that IL-6, derived from bone marrow-derived blood cells, is largely responsible for this response. PMID- 26818423 TI - Differential Levels of Tl1a Affect the Expansion and Function of Regulatory T Cells in Modulating Murine Colitis. AB - BACKGROUND: Expression of TL1A (tumor necrosis factor-like ligand 1A) is increased in patients with inflammatory bowel disease (IBD). Mice with elevated T cell expression of Tl1a (L-Tg) have increased regulatory T cells, yet develop worsened colitis and intestinal fibrosis. The aim of this study was to investigate the role of Tl1a in the differentiation and function of Tregs and their effects in modulating murine colitis. METHODS: Tl1a overexpressing L-Tg, Foxp3-mRFP (FIR)-LTg, and DR3KO-LTg mice were used for the study. In the L-Tg mice, Tl1a expressing cells can be identified by green fluorescent protein (GFP). RESULTS: We report that Foxp3 expression in the L-Tg mice is variable based on high or low level of Tl1a expression, referred to herein as GFPhigh and GFPlow T cells. Treg-specific suppressive molecules were highly expressed on the GFPlow Foxp3 Tregs and were significantly reduced on Tregs expressing high Tl1a. In vitro suppression function was significantly enhanced in the GFPlow compared with the GFPhigh Tregs. RAG mice cotransferred with either GFPlow or wild-type Tregs were protected from colitis. Furthermore, GFPlow Tregs lost the suppression function in the absence of DR3 (Death receptor 3). CONCLUSIONS: Tregs expressing low levels of Tl1a ameliorate murine colitis and promote the maintenance of Treg suppressor function in a DR3-dependent manner, partly due to a heightened regulatory program. These data reveal novel roles for differential levels of Tl1a in regulating T cell-mediated immune responses that have implications in understanding the pathogenesis of IBD. PMID- 26818425 TI - Short Bowel Syndrome and Intestinal Failure in Crohn's Disease. AB - Crohn's disease is a chronic and progressive inflammatory disorder of the gastrointestinal tract. Despite the availability of powerful immunosuppressants, many patients with Crohn's disease still require one or more intestinal resections throughout the course of their disease. Multiple resections and a progressive reduction in bowel length can lead to the development of short bowel syndrome, a form of intestinal failure that compromises fluid, electrolyte, and nutrient absorption. The pathophysiology of short bowel syndrome involves a reduction in intestinal surface area, alteration in the enteric hormonal feedback, dysmotility, and related comorbidities. Most patients will initially require parenteral nutrition as a primary or supplemental source of nutrition, although several patients may eventually wean off nutrition support depending on the residual gut anatomy and adherence to medical and nutritional interventions. Available surgical treatments focus on reducing motility, lengthening the native small bowel, or small bowel transplantation. Care of these complex patients with short bowel syndrome requires a multidisciplinary approach of physicians, dietitians, and nurses to provide optimal intestinal rehabilitation, nutritional support, and improvement in quality of life. PMID- 26818426 TI - Long-term Compliance with Oral 5-aminosalicylic Acid Therapy and Risk of Disease Recurrence in Patients with Ulcerative Colitis: A Population-based Cohort Study. AB - BACKGROUND: Noncompliance to long-term medical therapy is a well-known problem among patients treated for ulcerative colitis, but studies of long-term consequences in unselected patients are lacking. The authors aimed to determine the risk of recurrence according to long-term compliance with oral 5 aminosalicylic acid among unselected patients with ulcerative colitis. METHODS: The authors conducted a 7-year follow-up study of a population-based inception cohort of 243 Danish patients with ulcerative colitis diagnosed from 2003 to 2004. Compliance was defined as consumption of >=80% of prescribed oral 5 aminosalicylic acid. Data were collected from medical records and the Danish National Prescription Database. They performed Cox regression analysis with adjustments for demographic and clinical characteristics to examine risk of recurrence (defined by increased use of oral 5-Aminosalicylic Acid, other additional treatment, or colectomy) in compliant versus noncompliant patients. RESULTS: In total, 182 patients (75%) experienced at least 1 recurrence during follow-up. For the first year after diagnosis, risk of recurrence did not differ significantly between compliant and noncompliant patients. For 1 to 3 years (hazard ratio: 0.46, 95% CI, 0.33-0.63) and 3 to 8 years (hazard ratio: 0.42, 95% CI, 0.32-0.55) after diagnosis, risk of recurrence was significantly decreased among noncompliant patients compared with that of compliant patients. CONCLUSIONS: This unselected cohort study revealed a reverse association between compliance and recurrence of ulcerative colitis. This is unlikely to be explained by severe confounding because the authors were able to adjust for several demographic and clinical factors. Results may instead reflect that patients during recurrence-free periods through self-management choose not to take their medication. PMID- 26818427 TI - Epidemiology and risk factors for nosocomial bloodstream infections in solid organ transplants over a 10-year period. AB - BACKGROUND: Bloodstream infections (BSIs) are a leading cause of morbidity and mortality in solid organ transplantation (SOT). We sought to determine the types of nosocomial BSIs and risk factors for them in SOT. METHODS: Prospectively collected databases of all SOT and nosocomial BSIs occurring at our institution for a 10-year period were reviewed. RESULTS: From 2003-2012, we observed 157 nosocomial BSI episodes in 2257 SOTs, the majority of which were caused by staphylococci and enterococci (67.5%). The most common sources of BSI were central line, organ space, respiratory, and gastrointestinal. Kidney transplant patients had the lowest risk of acquiring a BSI compared with other SOT types. Lung transplant patients were at increased risk of methicillin-resistant Staphylococcus aureus BSI and heart transplant patients were at increased risk of a Candida albicans BSI, when compared to other organ transplant types. When coagulase-negative Staphylococcus (CoNS) or C. albicans was isolated, the central line was most often the source. The implementation of central-line bundles during the study period correlated temporally with a decreased rate of CoNS BSI. Over the 10-year period, vancomycin-resistant enterococci became the most common enterococcal BSI. Donor-positive cytomegalovirus status was associated with an increased risk of BSI, when compared to donor-negative patients. CONCLUSIONS: This study demonstrates the common sources, risk factors, and causative organisms of BSI, which can guide empiric antibiotic choices, and highlights areas where preventative interventions could be targeted to prevent nosocomial BSI in SOT. PMID- 26818428 TI - Fatty acids and small organic compounds bind to mineralo-organic nanoparticles derived from human body fluids as revealed by metabolomic analysis. AB - Nanoparticles entering the human body instantly become coated with a "protein corona" that influences the effects and distribution of the particles in vivo. Yet, whether nanoparticles may bind to other organic compounds remains unclear. Here we use an untargeted metabolomic approach based on ultra-performance liquid chromatography and quadruple time-of-flight mass spectrometry to identify the organic compounds that bind to mineral nanoparticles formed in human body fluids (serum, plasma, saliva, and urine). A wide range of organic compounds is identified, including fatty acids, glycerophospholipids, amino acids, sugars, and amides. Our results reveal that, in addition to the proteins identified previously, nanoparticles harbor an "organic corona" containing several fatty acids which may affect particle-cell interactions in vivo. This study provides a platform to study the organic corona of biological and synthetic nanoparticles found in the human body. PMID- 26818429 TI - Involution dependent changes in distribution and localization of bax, survivin, caspase-3, and calpain-1 in the rat endometrium. AB - The endometrial layer of the uterus is characterized by continuous cycle of cell growth and apoptosis in response to hormonal changes. Apoptosis is regulated by several apoptotic regulators, but their significance in involuting uterus has not been well understood. For that reason, aim of this study was to investigate possible role of apoptosis-related proteins (bax and survivin) and enzymes (caspase-3 and calpain-1) in the involuting uterus of the rat, using immunohistochemistry. Our results indicated cytoplasmic and nuclear immunostaining for bax, caspase-3, calpain-1 and survivin proteins were found in the endometrial epithelium and stromal cells such as fibroblasts, mast cells and macrophages, and blood vessels; however, calpain-1 immunoreactivity in the endometrial fibroblast was quite weak or absent. Supranuclear punctate bax immunolabelling was also observed in the endometrial fibroblasts and luminal and glandular epithelial cells from days 1st and 3rd following parturition, respectively. Although survivin was localized in the apical cytoplasm underneath the apical membrane of the luminal epithelium on the 1st and 3rd days, it was also localized in the apicolateral membrane and basal cytoplasm on the 10th and 15th days of involution. Immunostainigs demonstrated that expression patterns of all examined proteins varied with structural changes in the luminal epithelium, and number of immunopositive fibroblasts for bax, caspase-3 and survivin increased with advance of postpartum days and reached a maximum on postpartum days 10 and 15. These results suggest that the process of postpartum involution of endometrium may be regulated by apoptotic and non-apoptotic activity of bax, caspase-3, calpain-1, and survivin. PMID- 26818430 TI - Air-mode photonic crystal ring resonator on silicon-on-insulator. AB - In this report, we propose and demonstrate an air-mode photonic crystal ring resonator (PhCRR) on silicon-on-insulator platform. Air mode is utilized to confine the optical field into photonic crystal (PhC) air holes, which is confirmed by the three-dimensional finite-difference time-domain simulation. PhCRR structure is employed to enhance the light-matter interaction through combining the whispering-gallery mode resonance of ring resonator with the slow light effect in PhC waveguide. In the simulated and measured transmission spectra of air-mode PhCRR, nonuniform free spectral ranges are observed near the Brillouin zone edge of PhC, indicating the presence of the slow-light effect. A maximum group index of 27.3 and a highest quality factor of 14600 are experimentally obtained near the band edge. Benefiting from the strong optical confinement in the PhC holes and enhanced light-matter interaction in the resonator, the demonstrated air-mode PhCRR is expected to have potential applications in refractive index sensing, on-chip light emitting and nonlinear optics by integration with functional materials. PMID- 26818431 TI - A highly photoconductive composite prepared by incorporating polyoxometalate into perovskite for photodetection application. AB - A photoconductive perovskite-polyoxometalate composite was prepared for the first time by a facile low-temperature and solution-processed method, and this composite exhibited a significantly enhanced photoconductivity and photodetection performance due to introduction of polyoxometalate into the perovskite for fine energy-level matching and efficient charge transfer. PMID- 26818433 TI - Incomplete Disclosure of Potential Conflicts of Interest. PMID- 26818432 TI - Human mesenchymal and murine stromal cells support human lympho-myeloid progenitor expansion but not maintenance of multipotent haematopoietic stem and progenitor cells. AB - A major goal in haematopoietic stem cell (HSC) research is to define conditions for the expansion of HSCs or multipotent progenitor cells (MPPs). Since human HSCs/MPPs cannot be isolated, NOD/SCID repopulating cell (SRC) assays emerged as the standard for the quantification of very primitive haematopoietic cell. However, in addition to HSCs/MPPs, lympho-myeloid primed progenitors (LMPPs) were recently found to contain SRC activities, challenging this assay as clear HSC/MPP readout. Because our revised model of human haematopoiesis predicts that HSCs/MPPs can be identified as CD133(+)CD34(+) cells containing erythroid potentials, we investigated the potential of human mesenchymal and conventional murine stromal cells to support expansion of HSCs/MPPs. Even though all stromal cells supported expansion of CD133(+)CD34(+) progenitors with long-term myeloid and long-term lymphoid potentials, erythroid potentials were exclusively found within erythro-myeloid CD133(low)CD34(+) cell fractions. Thus, our data demonstrate that against the prevailing assumption co-cultures on human mesenchymal and murine stromal cells neither promote expansion nor maintenance of HSCs and MPPs. PMID- 26818434 TI - The All E. coli TX-TL Toolbox 2.0: A Platform for Cell-Free Synthetic Biology. AB - We report on and provide a detailed characterization of the performance and properties of a recently developed, all Escherichia coli, cell-free transcription and translation system. Gene expression is entirely based on the endogenous translation components and transcription machinery provided by an E. coli cytoplasmic extract, thus expanding the repertoire of regulatory parts to hundreds of elements. We use a powerful metabolism for ATP regeneration to achieve more than 2 mg/mL of protein synthesis in batch mode reactions, and more than 6 mg/mL in semicontinuous mode. While the strength of cell-free expression is increased by a factor of 3 on average, the output signal of simple gene circuits and the synthesis of entire bacteriophages are increased by orders of magnitude compared to previous results. Messenger RNAs and protein degradation, respectively tuned using E. coli MazF interferase and ClpXP AAA+ proteases, are characterized over a much wider range of rates than the first version of the cell free toolbox. This system is a highly versatile cell-free platform to construct complex biological systems through the execution of DNA programs composed of synthetic and natural bacterial regulatory parts. PMID- 26818435 TI - Surface activation of CNT Webs towards layer by layer assembly of biosensors. AB - Several surface activation methods such as chemical, electrochemical and plasma have been used for enhancing the electrochemical performance of carbon based electrodes for various applications. However, some of these surface activation methods may not be useful depending on the chemical and physical properties of the activated surface. Herein we investigate the surface activation of carbon nanotube (CNT) webs by electrochemical and plasma techniques to enhance their electrochemical performance and enable the fabrication of a biosensor using the layer-by-layer (LBL) approach. The pretreated CNT webs were characterized by SEM, TEM, Raman, XPS and electrochemical methods. TEM images and Raman analysis showed an increase in the level of surface defects upon pretreatment with higher number of defects after electrochemical pretreatment. XPS analysis showed an increase in the level of oxygen functional groups after pretreatment (4 to 5 times increase) which resulted in enhanced water wettability especially for plasma pretreated CNT webs. The pretreated CNT web electrodes also showed an enhanced electrochemical activity towards the oxidation and reduction of different redox probes with higher sensitivity for the electrochemically pretreated CNT web electrode that was accompanied by a higher level of noise in amperometric measurements. A highly linear response was obtained for the untreated and the electrochemically pretreated CNT web electrodes towards the amperometric detection of NADH (R(2) of 0.9996 and 0.9986 respectively) while a non-linear response was observed for the plasma pretreated CNT web electrode (R(2) of 0.8538). The pretreated CNT web electrodes enabled the fabrication of a LBL biosensor for alcohol detection with highest operational stability obtained for the plasma pretreated CNT web surface. PMID- 26818436 TI - Pseudogene transcripts: Participants in tumorigenicity and promising therapeutic targets. PMID- 26818437 TI - Abortion in modern health care: Considering the issues for health-care professionals. AB - This paper explores the challenging and contentious issue of abortion and its ethical, legal and political significance regarding public health. It is intended as an educational guide for health-care professionals. A comprehensive search strategy of international health, law and political source materials was undertaken in order to benchmark from international approaches to abortion. Test cases illustrate the application of legislation, ethical, political and cultural issues surrounding abortion. Abortion is a complex contemporary issue where balancing the well-being of both the mother and the unborn has prompted considerable international discourse. The right to life of the woman and the unborn continues to lie in tension. Ambiguity surrounds the concept of personhood, and the inception of human life prevails across many International jurisdictions. Health-care professionals must be well informed in order to respond safely and appropriately to a diverse range of clinical scenarios in which decisions regarding abortion are required. Research and evidence of test cases will better inform how abortion issues evolve and are managed. Ultimately, the abortion debate requires a balance between legislation and clinical governance. PMID- 26818438 TI - Modular, polymer-directed nanoparticle assembly for fabricating metamaterials. AB - We achieve the fabrication of plasmonic meta-atoms by utilizing a novel, modular approach to nanoparticle self-assembly that utilizes polymer templating to control meta-atom size and geometry. Ag nanocubes are deposited and embedded into a polymer thin-film, where the polymer embedding depth is used to dictate which nanocube faces are available for further nanocrystal binding. Horizontal and vertical nanocube dimers were successfully fabricated with remarkably high yield using a bifunctional molecular linker to bind a second nanocube. Surface plasmon coupling can be readily tuned by varying the size, shape, and orientation of the second nanoparticle. We show that meta-atoms can be fabricated to exhibit angle- and polarization-dependent optical properties. This scalable technique for meta atom assembly can be used to fabricate large-area metasurfaces for polarization- and phase-sensitive applications, such as optical sensing. PMID- 26818439 TI - Targeting glioblastoma stem cells (GSCs) with peroxisome proliferator-activated receptor gamma (PPARgamma) ligands. AB - Glioblastoma multiforme (GBM), also known as glioblastoma, is the most common and aggressive brain tumor. GBM has a poor survival rate and high resistance to standard therapy, leading to recurrence and metastasis to adjacent normal regions. Glioblastoma stem cells (GSCs) are regarded as an emerging target for therapy of GBM. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that functions in a variety of cancers and in normal adipocyte differentiation. The newly discovered connection between PPARgamma ligands and cancer stem cells (CSCs) raises important implications for the potential therapeutic use of synthetic PPARgamma ligands, such as thiazolidinediones (TZDs), in glioblastoma. Here, I hypothesize that synthetic PPARgamma ligands serve to modulate stemness-related molecules and several signaling pathway in GSCs and I propose potential experimental approaches to investigate the effects of these ligands on GSCs in vitro and in vivo. PMID- 26818441 TI - Adult stem cells: Hair stem cells born without a home. PMID- 26818442 TI - A quantitative analysis of hydraulic interaction processes in stream-aquifer systems. AB - The hydraulic relationship between the stream and aquifer can be altered from hydraulic connection to disconnection when the pumping rate exceeds the maximum seepage flux of the streambed. This study proposes to quantitatively analyze the physical processes of stream-aquifer systems from connection to disconnection. A free water table equation is adopted to clarify under what conditions a stream starts to separate hydraulically from an aquifer. Both the theoretical analysis and laboratory tests have demonstrated that the hydraulic connectedness of the stream-aquifer system can reach a critical disconnection state when the horizontal hydraulic gradient at the free water surface is equal to zero and the vertical is equal to 1. A boundary-value problem for movement of the critical point of disconnection is established for an analytical solution of the inverted water table movement beneath the stream. The result indicates that the maximum distance or thickness of the inverted water table is equal to the water depth in the stream, and at a steady state of disconnection, the maximum hydraulic gradient at the streambed center is 2. This study helps us to understand the hydraulic phenomena of water flow near streams and accurately assess surface water and groundwater resources. PMID- 26818440 TI - Pluripotent stem cells in disease modelling and drug discovery. AB - Experimental modelling of human disorders enables the definition of the cellular and molecular mechanisms underlying diseases and the development of therapies for treating them. The availability of human pluripotent stem cells (PSCs), which are capable of self-renewal and have the potential to differentiate into virtually any cell type, can now help to overcome the limitations of animal models for certain disorders. The ability to model human diseases using cultured PSCs has revolutionized the ways in which we study monogenic, complex and epigenetic disorders, as well as early- and late-onset diseases. Several strategies are used to generate such disease models using either embryonic stem cells (ES cells) or patient-specific induced PSCs (iPSCs), creating new possibilities for the establishment of models and their use in drug screening. PMID- 26818443 TI - Role of the D1-D2 Linker of Human VCP/p97 in the Asymmetry and ATPase Activity of the D1-domain. AB - Human AAA(+) protein p97 consists of an N-domain and two tandem ATPase domains D1 and D2, which are connected by the N-D1 and the D1-D2 linkers. Inclusion of the D1-D2 linker, a 22-amino acid peptide, at the end of p97 N-D1 truncate has been shown to activate ATP hydrolysis of its D1-domain, although the mechanism of activation remains unclear. Here, we identify the N-terminal half of this linker, highly conserved from human to fungi, is essential for the ATPase activation. By analyzing available crystal structures, we observed that the D1-D2 linker is capable of inducing asymmetry in subunit association into a p97 hexamer. This observation is reinforced by two new crystal structures, determined in the present work. The effect of D1-D2 linker on the ATPase activity of the D1-domain is correlated to the side-chain conformation of residue R359, a trans-acting arginine-finger residue essential for ATP hydrolysis of the D1-domain. The activation in D1-domain ATPase activity by breaking perfect six-fold symmetry implies functional importance of asymmetric association of p97 subunits, the extent of which can be determined quantitatively by the metric Asymmetric Index. PMID- 26818444 TI - MatP regulates the coordinated action of topoisomerase IV and MukBEF in chromosome segregation. AB - The Escherichia coli SMC complex, MukBEF, forms clusters of molecules that interact with the decatenase topisomerase IV and which are normally associated with the chromosome replication origin region (ori). Here we demonstrate an additional ATP-hydrolysis-dependent association of MukBEF with the replication termination region (ter). Consistent with this, MukBEF interacts with MatP, which binds matS sites in ter. MatP displaces wild-type MukBEF complexes from ter, thereby facilitating their association with ori, and limiting the availability of topoisomerase IV (TopoIV) at ter. Displacement of MukBEF is impaired when MukB ATP hydrolysis is compromised and when MatP is absent, leading to a stable association of ter and MukBEF. Impairing the TopoIV-MukBEF interaction delays sister ter segregation in cells lacking MatP. We propose that the interplay between MukBEF and MatP directs chromosome organization in relation to MukBEF clusters and associated topisomerase IV, thereby ensuring timely chromosome unlinking and segregation. PMID- 26818446 TI - Surgery for bicuspid valve aortopathy clarified--for now. PMID- 26818445 TI - Cardiac magnetic resonance radiofrequency tissue tagging for diagnosis of constrictive pericarditis: A proof of concept study. AB - OBJECTIVE: Invasive cardiac catheterization is the venerable "gold standard" for diagnosing constrictive pericarditis. However, its sensitivity and specificity vary dramatically from center to center. Given the ability to unequivocally define segments of the pericardium with the heart via radiofrequency tissue tagging, we hypothesize that cardiac magnetic resonance has the capability to be the new gold standard. METHODS: All patients who were referred for cardiac magnetic resonance evaluation of constrictive pericarditis underwent cardiac magnetic resonance radiofrequency tissue tagging to define visceral-parietal pericardial adherence to determine constriction. This was then compared with intraoperative surgical findings. Likewise, all preoperative cardiac catheterization testing was reviewed in a blinded manner. RESULTS: A total of 120 patients were referred for clinical suspicion of constrictive pericarditis. Thirty-nine patients were defined as constrictive pericarditis positive solely via radiofrequency tissue-tagging cardiac magnetic resonance, of whom 21 were positive, 4 were negative, and 1 was equivocal for constrictive pericarditis, as defined by cardiac catheterization. Of these patients, 16 underwent pericardiectomy and were surgically confirmed. There was 100% agreement between cardiac magnetic resonance-defined constrictive pericarditis positivity and postsurgical findings. No patients were misclassified by cardiac magnetic resonance. In regard to the remaining constrictive pericarditis-positive patients defined by cardiac magnetic resonance, 10 were treated medically, declined, were ineligible for surgery, or were lost to follow-up. Long-term follow-up of those who were constrictive pericarditis negative by cardiac magnetic resonance showed no early or late crossover to the surgery arm. CONCLUSIONS: Cardiac magnetic resonance via radiofrequency tissue tagging offers a unique, efficient, and effective manner of defining clinically and surgically relevant constrictive pericarditis. Specifically, no patient who was identified with constriction via cardiac magnetic resonance underwent inappropriate sternotomy. However, catheterization had substantial and unacceptable false-positive and false negative rates with important clinical ramifications. PMID- 26818447 TI - Effect of metformin and sitagliptin on doxorubicin-induced cardiotoxicity in adult male albino rats. AB - The use of doxorubicin (DOX) as an antitumor therapeutic agent is limited due to its cardiotoxic effects. Metformin (Met) and sitagliptin (Sitg) are suggested to improve cardiac function. The present study aimed to determine the potential protective effects of Met and Sitg on DOX-induced cardiotoxicity. Rats were divided into six groups: groups I, II, and III received normal saline, Met, and Sitg, respectively. Groups IV, V, and VI received DOX only, Met + DOX, and Sitg + DOX, respectively. Heart tissue was used for biochemical assays which measured cardiac reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and tumor necrosis factor alpha (TNF-alpha). Serum creatinine kinase (CK) and lactate dehydrogenase (LDH) were also measured. The heart apex was prepared for histological (hematoxylin and eosin) and immunohistochemical examination. Intoxication of DOX was associated with a significant elevation in serum CK-MB and LDH, reduction in cardiac GSH, and increased TBARS and TNF-alpha compared to the controls. Administration of Met or Sitg to DOX-intoxicated rats suppressed serum CK-MB and LDH. Moreover, cardiac GSH was elevated with decreased TBARS and TNF-alpha. These results were confirmed by histological study. Met and Sitg caused inhibition of caspase 3 and upregulation of B-cell lymphoma 2 (Bcl-2) expression in DOX-intoxicated animals. Sitg was found to exert a significantly better protective effect compared to that of Met. It was concluded that Sitg might be more effective than Met in reducing myocardial injury in DOX-induced cardiotoxicity in rats. PMID- 26818448 TI - Improving quality and outcomes of coronary artery bypass grafting procedures. AB - The evolution in the approach, clinical care and outcomes of ischemic heart disease, has been dramatic over the past decade. Optimizing medical therapy initially and throughout the care delivery process has been transformative. The addition of new physiologic data to the traditional anatomic framework for diagnosis and therapy of more extensive stable ischemic heart disease (SIHD) enables quality and outcomes improvements in this patient population overall and in the patient subsets of acute coronary syndrome and SIHD. In patients undergoing coronary artery bypass grafting (CABG), these developments have changed the objective goal of surgical revascularization over this time interval. This review discusses the opportunities for quality and outcomes improvement in CABG, in the context of SIHD overall. PMID- 26818449 TI - Prospective Use of a Standardized Nonoperative Early Weightbearing Protocol for Achilles Tendon Rupture: 17 Years of Experience. AB - BACKGROUND: Acute traumatic rupture of the Achilles tendon can be treated operatively or nonoperatively. Throughout the literature, there is no consensus regarding the optimal treatment protocol. PURPOSE: To report on 17 years of experience with treating this injury with a standardized nonoperative treatment protocol. STUDY DESIGN: Case Series; Level of evidence, 4. METHODS: The treatment protocol was based on a combination of an equinus cast and rehabilitation boot, which promoted immediate full weightbearing and early functional rehabilitation. A total of 171 patients were consecutively treated and prospectively followed from 1996 to 2013. Assessed were subjective parameters such as pain, loss of strength, return to previous activity level, meteosensitivity, and general satisfaction with the treatment outcome. Clinical assessment included testing of plantar flexion strength and endurance, calf circumference, and tendon length. Subjective and clinical parameters were then used to calculate a modified Thermann score. The correlation between tendon lengthening and function was calculated using the Pearson correlation coefficient. RESULTS: A total of 114 patients were followed for a minimum of 12 months (mean, 27 +/- 20 months; range, 12-88 months). The mean Thermann score was 82 +/- 13 (range, 41-100), and subjective satisfaction was rated "very good" and "good" in 90%. An inverse correlation was found between tendon length and muscle strength (R = -0.3). There were 11 reruptures (8 with and 3 without an adequate trauma). General complications were 5 deep venous thromboses, 1 complex regional pain syndrome, and minor problems such as transient heel pain (n = 3), heel numbness (n = 1), and cast-associated skin abrasions (n = 4). CONCLUSION: Seventeen years of experience with a nonoperative treatment protocol for acute rupture of the Achilles tendon confirmed good functional outcome and patient satisfaction. Reruptures mostly occurred with new traumatic events in the vulnerable phase from 6 to 12 weeks after the initial injury. Muscle strength correlated to tendon length, making its assessment a crucial follow-up parameter. The protective equinus cast and boot can protect against excessive tendon lengthening during the healing process. PMID- 26818450 TI - Biomechanical Effects of a Horizontal Medial Meniscal Tear and Subsequent Leaflet Resection. AB - BACKGROUND: Horizontal, degenerative tears of the medial meniscus and subsequent meniscectomy can compromise the biomechanical function of the meniscus in load transmission and weightbearing, leading to the development of radiographic and symptomatic tibiofemoral arthritis. HYPOTHESIS: Resection of both leaflets of a horizontal medial meniscal tear will increase peak contact pressures and decrease contact areas in comparison with resection of only the inferior leaflet. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve fresh-frozen human cadaveric knees had tibiofemoral peak contact pressures and contact areas under an 1800-N axial load measured by Tekscan in the control state. A horizontal tear was created in the posterior horn of the medial meniscus, and the knees were retested. The knees were tested a third time after resection of the inferior leaflet (single leaflet) and a final time after resection of the superior leaflet (both leaflets). The Friedman test was used to test for group differences in peak pressure (psi) and contact area (mm(2)) between test conditions (native, tear, inferior leaflet resection, and resection of both leaflets). RESULTS: For the medial compartment, there was a statistically significant difference in peak pressure (P = .03) but not in contact area (P = .70) between testing conditions. Median peak pressure in the medial compartment was significantly greater for resection of both leaflets compared with the tear (406.5 vs 294.7 psi, respectively; P = .002). Median contact area in the medial compartment was greatest for resection of both leaflets (602.7 mm(2)), but there were no statistically significant differences between test conditions (P = .70). For the lateral compartment, there were no statistically significant differences in peak pressure (P = .99) or contact area (P = .77) between test conditions. CONCLUSION: Resection of a single inferior leaflet after a horizontal medial meniscal tear preserves much of the original biomechanical function of the meniscus. Resection of both leaflets leads to a significant increase in contact pressure dispersed over the same contact area, which results in an undesirable biomechanical environment. CLINICAL RELEVANCE: Arthroscopic inferior leaflet resection is a viable option for providing symptomatic relief of horizontal medial meniscal tears and preserves the ability of the meniscus to absorb axial loading on the knee joint, theoretically decreasing the risk of subsequent osteoarthritis. PMID- 26818451 TI - Revision Meniscal Surgery in Children and Adolescents: Risk Factors and Mechanisms for Failure and Subsequent Management. AB - BACKGROUND: The mechanisms of failure and risk factors for failed meniscal surgery in children and adolescents have not been well described. PURPOSE: To investigate the risk factors, mechanisms of failure, and subsequent operative management for revision meniscal surgery in a pediatric population, as well as to identify the local incidence of failed meniscal surgery. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: All patients younger than 20 years who had arthroscopic management for meniscal injuries at a single institution between 2008 and 2012 underwent retrospective review. Demographic data and intraoperative findings at the time of the initial surgery were documented. All patients undergoing a second procedure on the same meniscus were further analyzed. Multivariate logistic regression with purposeful selection was performed to identify independent risk factors for revision meniscal surgery. RESULTS: Arthroscopic knee surgery was performed on 293 patients and 324 menisci, including 129 primary repairs, 149 primary partial meniscectomies, and 46 discoid saucerizations +/- stabilization. At a mean of 40 months (range, 19-62 months) after surgery, 13% of all menisci required a revision procedure. The primary repair cohort had the highest failure rate (18%), followed by the primary discoid saucerization cohort (15%) and the partial meniscectomy cohort (7%). Multivariate analysis indicated that meniscal repair was predictive of retear (odds ratio, 2.04 [95% CI, 1.01-4.1]; P = .046), and children with an open physis and a bucket handle tear had the highest retear rate of 46% (P = .039). Independent variables shown to have no significant relationship to revision meniscal surgery included age, sex, body mass index, extremity side, laterality (medial-lateral), time to repair, tear location, and associated ligament reconstruction. The most common indication for revision surgery was an acute reinjury during intense physical activity. Revision procedures were performed at a mean of 14 months after the index procedure, and the majority of failures (83%) were identified within 1 year. Of patients undergoing a revision surgery, 44% underwent a further debridement, whereas 56% underwent a repair. CONCLUSION: The success rate of meniscal surgery is 87% in children and adolescents. The revision rate was higher when repair was attempted in the index procedure, particularly in those children with open physes and bucket-handle tears. Most failures are the result of an acute reinjury within 1 year, and nearly half will require debridement of the retorn meniscus. PMID- 26818452 TI - Latarjet Procedure for Anterior Shoulder Instability Due to Tramadol-Induced Seizures: A Multicenter Study. AB - BACKGROUND: Seizures, commonly due to epilepsy, are known to cause shoulder instability. Tramadol addiction has recently been found to induce seizures in patients who exceed the recommended dose. Because of the easy accessibility and low cost of tramadol, an increasingly alarming phenomenon of tramadol abuse has been demonstrated in recent years. PURPOSE/HYPOTHESIS: The purpose of this multicenter study was to investigate shoulder instability resulting from tramadol induced seizure (TIS) as well as to recommended management for such shoulder instability. The hypothesis was that TIS leads to anterior shoulder dislocations with major bony defects, which favors bony reconstructive procedures as a suitable method of treatment. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This prospective case series study was conducted on 73 patients (78 shoulders) who presented with anterior shoulder dislocations and a clear history of tramadol abuse. The mean age of the patients was 26.8 years, and the mean number of dislocations was 14. The mean duration of addiction was 17 months, with a mean dose of 752 mg of tramadol hydrochloride per day. Glenoid and humeral bone loss ranged from 15% to 35% and from 15% to 40%, respectively. The mean follow-up period was 28 months. All patients underwent an open Latarjet procedure. RESULTS: Postoperative mean Rowe score and American Shoulder and Elbow Surgeons score at final follow-up (24 months) improved significantly from 20 to 84 and from 44 to 91, respectively (P < .05). The patient satisfaction rate reached 95%, and the mean period of return to work was 12.8 weeks. Five patients (9%) had postoperative seizures due to relapse of the tramadol abuse, but only 3 patients (5%) had redislocations with nonunion or breakage of the graft or hardware. CONCLUSION: Tramadol addiction has evolved as an important cause of seizures that can result in shoulder dislocation. Anterior shoulder instability with TIS occurs mainly with higher levels of addiction and results in significant humeral and/or glenoid bone defects. The Latarjet procedure is recommended for these patients, after control of addiction, and provides 95% satisfaction at midterm follow-up. PMID- 26818453 TI - Comprehensive prediction of lncRNA-RNA interactions in human transcriptome. AB - MOTIVATION: Recent studies have revealed that large numbers of non-coding RNAs are transcribed in humans, but only a few of them have been identified with their functions. Identification of the interaction target RNAs of the non-coding RNAs is an important step in predicting their functions. The current experimental methods to identify RNA-RNA interactions, however, are not fast enough to apply to a whole human transcriptome. Therefore, computational predictions of RNA-RNA interactions are desirable, but this is a challenging task due to the huge computational costs involved. RESULTS: Here, we report comprehensive predictions of the interaction targets of lncRNAs in a whole human transcriptome for the first time. To achieve this, we developed an integrated pipeline for predicting RNA-RNA interactions on the K computer, which is one of the fastest super computers in the world. Comparisons with experimentally-validated lncRNA-RNA interactions support the quality of the predictions. Additionally, we have developed a database that catalogs the predicted lncRNA-RNA interactions to provide fundamental information about the targets of lncRNAs. PMID- 26818454 TI - Development and Characterization of Potent Cyclic Acyldepsipeptide Analogues with Increased Antimicrobial Activity. AB - The problem of antibiotic resistance has prompted the search for new antibiotics with novel mechanisms of action. Analogues of the A54556 cyclic acyldepsipeptides (ADEPs) represent an attractive class of antimicrobial agents that act through dysregulation of caseinolytic protease (ClpP). Previous studies have shown that ADEPs are active against Gram-positive bacteria (e.g., MRSA, VRE, PRSP (penicillin-resistant Streptococcus pneumoniae)); however, there are currently few studies examining Gram-negative bacteria. In this study, the synthesis and biological evaluation of 14 novel ADEPs against a variety of pathogenic Gram negative and Gram-positive organisms is outlined. Optimization of the macrocyclic core residues and N-acyl side chain culminated in the development of 26, which shows potent activity against the Gram-negative species Neisseria meningitidis and Neisseria gonorrheae and improved activity against the Gram-positive organisms Staphylococcus aureus and Enterococcus faecalis in comparison with known analogues. In addition, the co-crystal structure of an ADEP-ClpP complex derived from N. meningitidis was solved. PMID- 26818455 TI - Systems consultation: protocol for a novel implementation strategy designed to promote evidence-based practice in primary care. AB - BACKGROUND: Adoption of evidence-based practices takes place at a glacial place in healthcare. This research will pilot test an innovative implementation strategy - systems consultation -intended to speed the adoption of evidence-based practice in primary care. The strategy is based on tenets of systems engineering and has been extensively tested in addiction treatment. Three innovations have been included in the strategy - translation of a clinical practice guideline into a checklist-based implementation guide, the use of physician peer coaches ('systems consultants') to help clinics implement the guide, and a focus on reducing variation in practices across prescribers and clinics. The implementation strategy will be applied to improving opioid prescribing practices in primary care, which may help ultimately mitigate the increasing prevalence of opioid abuse and addiction. METHODS/DESIGN: The pilot test will compare four intervention clinics to four control clinics in a matched-pairs design. A leading clinical guideline for opioid prescribing has been translated into a checklist based implementation guide in a systematic process that involved experts who wrote the guideline in consultation with implementation experts and primary care physicians. Two physicians with expertise in family and addiction medicine are serving as the systems consultants. Each systems consultant will guide two intervention clinics, using two site visits and follow-up communication by phone and email, to implement the translated guideline. Mixed methods will be used to test the feasibility, acceptability, and preliminary effectiveness of the implementation strategy in an evaluation that meets standards for 'fully developed use' of the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, Maintenance). The clinic will be the primary unit of analysis. DISCUSSION: The systems consultation implementation strategy is intended to generalize to the adoption of other clinical guidelines. This pilot test is intended to prepare for a large randomized clinical trial that will test the strategy against other implementation strategies, such as audit/feedback and academic detailing, used to close the gap between knowledge and practice. The systems consultation approach has the potential to shorten the famously long time it takes to implement evidence-based practices and clinical guidelines in healthcare. PMID- 26818457 TI - Precision of fibula positioning guide in mandibular reconstruction with a fibula graft. AB - BACKGROUND: This study examined the usefulness of the fibula positioning guide for boosting the accuracy of mandible reconstructions. METHODS: Thirty mandibular rapid prototype (RP) models were allocated to experimental (N = 15) and control (N = 15) groups. For reference, we prepared a reconstructed mandibular RP model with a three-dimensional printer, based on surgical simulation. In the experimental group, a fibula positioning guide template and fibula cutting guide, based on simulation, were used to reconstruct the mandible with a fibula graft. In the control group, only the fibula cutting guide, with reference to the reconstructed RP mandible model, was used to reconstruct the mandible with a fibula graft. The two mandibular reconstructions were compared to the surgical simulation by registering images with the non-surgical right side of the mandible. On the reconstructed side, 3D measurements were compared between the surgical simulation and actual surgery, and the sum of differences was taken as the total error. RESULTS: The combined use of the fibula cutting and positioning guides produced a smaller total error (mean +/- SD: 10.0 +/- 7.9 mm) than the fibula cutting guide alone (12.8 +/- 8.8 mm; p = 0.015). The greatest point error was the vertical error at the mesial point of the anterior fibula segment. The anteroposterior and lateral errors were not significantly different between groups. These results showed that these two methods were not significantly different, except in the total and vertical errors. CONCLUSIONS: Considering the CAD/CAM processes required for creating positioning devices, the benefit provided with a positioning guide justified its use over the fibula cutting guide alone. PMID- 26818456 TI - UbiSite: incorporating two-layered machine learning method with substrate motifs to predict ubiquitin-conjugation site on lysines. AB - BACKGROUND: The conjugation of ubiquitin to a substrate protein (protein ubiquitylation), which involves a sequential process--E1 activation, E2 conjugation and E3 ligation, is crucial to the regulation of protein function and activity in eukaryotes. This ubiquitin-conjugation process typically binds the last amino acid of ubiquitin (glycine 76) to a lysine residue of a target protein. The high-throughput of mass spectrometry-based proteomics has stimulated a large-scale identification of ubiquitin-conjugated peptides. Hence, a new web resource, UbiSite, was developed to identify ubiquitin-conjugation site on lysines based on large-scale proteome dataset. RESULTS: Given a total of 37,647 ubiquitin-conjugated proteins, including 128,026 ubiquitylated peptides, obtained from various resources, this study carries out a large-scale investigation on ubiquitin-conjugation sites based on sequenced and structural characteristics. A TwoSampleLogo reveals that a significant depletion of histidine (H), arginine (R) and cysteine (C) residues around ubiquitylation sites may impact the conjugation of ubiquitins in closed three-dimensional environments. Based on the large-scale ubiquitylation dataset, a motif discovery tool, MDDLogo, has been adopted to characterize the potential substrate motifs for ubiquitin conjugation. Not only are single features such as amino acid composition (AAC), positional weighted matrix (PWM), position-specific scoring matrix (PSSM) and solvent-accessible surface area (SASA) considered, but also the effectiveness of incorporating MDDLogo-identified substrate motifs into a two-layered prediction model is taken into account. Evaluation by five-fold cross-validation showed that PSSM is the best feature in discriminating between ubiquitylation and non-ubiquitylation sites, based on support vector machine (SVM). Additionally, the two-layered SVM model integrating MDDLogo-identified substrate motifs could obtain a promising accuracy and the Matthews Correlation Coefficient (MCC) at 81.06% and 0.586, respectively. Furthermore, the independent testing showed that the two-layered SVM model could outperform other prediction tools, reaching at 85.10% sensitivity, 69.69% specificity, 73.69% accuracy and the 0.483 of MCC value. CONCLUSION: The independent testing result indicated the effectiveness of incorporating MDDLogo-identified motifs into the prediction of ubiquitylation sites. In order to provide meaningful assistance to researchers interested in large-scale ubiquitinome data, the two-layered SVM model has been implemented onto a web-based system (UbiSite), which is freely available at http://csb.cse.yzu.edu.tw/UbiSite/ . Two cases given in the UbiSite provide a demonstration of effective identification of ubiquitylation sites with reference to substrate motifs. PMID- 26818458 TI - Developing a Scientific Virtue-Based Approach to Science Ethics Training. AB - Responsible conduct of research training typically includes only a subset of the issues that ought to be included in science ethics and sometimes makes ethics appear to be a set of externally imposed rules rather than something intrinsic to scientific practice. A new approach to science ethics training based upon Pennock's notion of the scientific virtues may help avoid such problems. This paper motivates and describes three implementations-theory-centered, exemplar centered, and concept-centered-that we have developed in courses and workshops to introduce students to this scientific virtue-based approach. PMID- 26818460 TI - Ocular surface mucins and local inflammation--studies in genetically modified mouse lines. AB - Mucins locate to the apical surfaces of all wet-surfaced epithelia including ocular surface. The functions of the mucins include anti-adhesive, lubrication, water retention, allergens and pathogen barrier function. Ocular surface pathologies, i.e. dry eye syndrome or allergic conjunctivitis, are reportedly associated with alteration of expression pattern of mucin components. Recent investigations indicated anti-bacterial adhesion or anti-inflammatory effects of members of mucins in non-ocular tissues, i.e., gastrointestinal tracts or airway tissues, by using genetically modified mouse lines that lacks an expression of a mucin member. However, examination of ocular phenotypes of each of mucin gene ablated mouse lines has not yet fully performed. Muc16-deficient mouse is associated with spontaneous subclinical inflammation in conjunctiva. The article reviews the roles of mucin members in modulation of local inflammation in mucous membrane tissues and phenotype of mouse lines with the loss of a mucin gene. Analysis of ocular surface of mucin-gene related mutant mouse lines are to be further performed. PMID- 26818461 TI - Ruthenium nanoparticles decorated curl-like porous carbons for high performance supercapacitors. AB - The synthesis of highly dispersed and stable ruthenium nanoparticles (RuNPs; ca. 2-3 nm) on porous activated carbons derived from Moringa Oleifera fruit shells (MOC) is reported and were exploited for supercapacitor applications. The Ru/MOC composites so fabricated using the biowaste carbon source and ruthenium acetylacetonate as the co-feeding metal precursors were activated at elevated temperatures (600-900 (o)C) in the presence of ZnCl2 as the pore generating and chemical activating agent. The as-prepared MOC carbonized at 900 (o)C was found to possess a high specific surface area (2522 m(2) g(-1)) and co-existing micro- and mesoporosities. Upon incorporating RuNPs, the Ru/MOC nanocomposites loaded with modest amount of metallic Ru (1.0-1.5 wt%) exhibit remarkable electrochemical and capacitive properties, achiving a maximum capacitance of 291 F g(-1) at a current density of 1 A g(-1) in 1.0 M H2SO4 electrolyte. These highly stable and durable Ru/MOC electrodes, which can be facily fabricated by the eco-friendly and cost-effective route, should have great potentials for practical applications in energy storage, biosensing, and catalysis. PMID- 26818459 TI - Oral hyaluronan relieves knee pain: a review. AB - Hyaluronan (HA) is a component that is particularly abundant in the synovial fluid. Randomized, double-blinded, placebo-controlled trials carried out between 2008 and 2015 have proven the effectiveness of HA for the treatment of symptoms associated with synovitis, and particularly, knee pain, relief of synovial effusion or inflammation, and improvement of muscular knee strength. The mechanism by which HA exerts its effects in the living body, specifically receptor binding in the intestinal epithelia, has gradually been clarified. This review examines the effects of HA upon knee pain as assessed in clinical trials, as well as the mechanism of these effects and the safety of HA. PMID- 26818462 TI - Enhanced susceptibility to seizures modulated by high interleukin-1beta levels during early life malnutrition. AB - Early malnutrition in life has permanent consequences on brain development and has been suggested to influence seizure susceptibility. Despite malnutrition is not a direct cause of seizures, we hypothesize that malnutrition may modulate inflammatory response and result in cerebral vulnerability to seizures. In this study, we provide evidence that malnutrition may increase susceptibility to seizures in the postnatal period by interleukin-1beta (IL-1beta) in the hippocampus. Malnourished rats were maintained on a nutritional deprivation regimen from postnatal day 1 (P1) to P10. From P7 to P10, the threshold to seizures induced by flurothyl was used as an index of seizure susceptibility. ELISA and western blot was performed to evaluate levels of IL-1beta, IL-1R1, PSD 95 and synapsin. The role of inflammation in the changes of seizure threshold was studied with inhibitors of IL-1beta and IL-1R1. A significant decrease in body weight and seizure threshold was observed in postnatal malnourished rats. Early malnutrition modulates inflammation by high levels of IL-1beta in hippocampus and in serum. Furthermore, our malnutrition paradigm induced an increase in corticosterone levels. Injection of IL-1beta and IL-1R1 inhibitors before seizure induction augments seizure threshold in malnourished rats similar to nourished group. Malnutrition did not change PSD-95 and synapsin expression in the hippocampus. We suggest that malnutrition-induced inflammation might contribute to seizure susceptibility in the postnatal period. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1150-1159, 2016. PMID- 26818463 TI - Health status, geriatric syndromes and prescription of oral anticoagulant therapy in elderly medical inpatients with atrial fibrillation. AB - AIM: The aim of the present study was to investigate the prevalence of geriatric syndromes among older medical inpatients with atrial fibrillation, and their association with use of vitamin K antagonists. METHODS: A retrospective study of patients aged >=65 years discharged with a diagnosis of atrial fibrillation from the Acute Geriatric Ward was carried out. Stroke and bleeding risk were evaluated according to the CHA2 DS2 -VASC and HAS-BLED scores. Comorbidity, cognitive status, functional autonomy and contraindications to vitamin K antagonists were also considered. RESULTS: Atrial fibrillation was documented in 1078 of 3650 patients (29.5%, mean age 83.4 +/- 6.6 years, 60.3% women). Contraindications to vitamin K antagonists were documented in 24.9% of patients. Prescription of vitamin K antagonists at discharge was 37.8% and 47.9%, in the overall sample and in those without contraindications, respectively. In the overall sample, prescription of vitamin K antagonists was associated with younger age, permanent/persistent atrial fibrillation, home discharge, less comorbidity, higher hemoglobin levels, better functional independence, known atrial fibrillation at admission and lower HAS-BLED score. Among patients without contraindications to vitamin K antagonists, their use at discharge was independently associated with younger age, permanent/persistent atrial fibrillation, home discharge, higher hemoglobin levels and CHA2DS2-VASC score, better functional autonomy, and greater number of drugs. CONCLUSIONS: We showed a high prevalence of atrial fibrillation among older medical inpatients, who have a poor health status and a high prevalence of geriatric syndromes. Vitamin K antagonists were prescribed in less than half of the patients; underuse was mainly accounted for by a high prevalence of comorbidities/contraindications, poor health status and limited functional autonomy. Geriatr Gerontol Int 2017; 17: 416-423. PMID- 26818464 TI - Investigating the roots of successful IT adoption processes - an empirical study exploring the shared awareness-knowledge of Directors of Nursing and Chief Information Officers. AB - BACKGROUND: The majority of health IT adoption research focuses on the later stages of the IT adoption process: namely on the implementation phase. The first stage, however, which is defined as the knowledge-stage, remains widely unobserved. Following Rogers' Diffusion of Innovation Theory (DOI) this paper presents a research framework to examine the possible lack of shared IT awareness knowledge, i.e. an information gradient, of two crucial stakeholders, the Chief Information Officer (CIO) and the Director of Nursing (DoN). This study shall answer the following research questions: (1.) Does this gradient exist? (2.) Which direction does it have? (3.) Are certain health IT (HIT) attributes associated with a potential gradient? (4.) Which determinants of diffusion go along with this gradient? METHOD: Results of two surveys that focused on the topic "IT support of clinical workflows" from the viewpoint of CIOs and DoNs with corresponding datasets from 75 hospitals were used in a secondary data analysis. The gradient was operationalised by measuring the disagreement of CIOs and DoNs on the availability and implementation status of 29 IT functions. HIT attributes tested were relevance and market penetration of the IT functions, determinants of diffusion were inter-professional leadership and IT service density. RESULTS: The analysis revealed a significant disagreement on the availability of 9 out of 29 HIT functions. In 23 HIT functions, the CIOs reported a higher implementation status than the DoNs, which pointed to a trend for a unidirectional gradient. The disagreement was significantly lower when the relevance of the IT function was high. Both determinants of diffusion correlated significantly negative with the degree of disagreement. CONCLUSION: This is the first study to empirically examine shared awareness-knowledge of two IT-stakeholders that are crucial for triggering IT adoption on the frontline level in hospitals. It could be shown that a gradient and thus a lack of shared awareness-knowledge existed and was associated with certain factors. In conclusion, hospitals should implement improved cooperation between IT staff and clinicians and IT service density when establishing the prerequisites for successful IT adoption processes. PMID- 26818465 TI - Changing clinical patterns in rheumatoid arthritis management over two decades: sequential observational studies. AB - BACKGROUND: Rheumatoid arthritis (RA) treatment paradigms have shifted over the last two decades. There has been increasing emphasis on combination disease modifying anti-rheumatic drug (DMARD) therapy, newer biologic therapies have become available and there is a greater focus on achieving remission. We have evaluated the impact of treatment changes on disease activity scores for 28 joints (DAS28) and disability measured by the health assessment questionnaire scores (HAQ). METHODS: Four cross-sectional surveys between 1996 and 2014 in two adjacent secondary care rheumatology departments in London evaluated changes in drug therapy, DAS28 and its component parts and HAQ scores (in three surveys). Descriptive statistics used means and standard deviations (SD) or medians and interquartile ranges (IQR) to summarise changes. Spearman's correlations assessed relationships between assessments. RESULTS: 1324 patients were studied. Gender ratios, age and mean disease duration were similar across all cohorts. There were temporal increases in the use of any DMARDs (rising from 61% to 87% of patients from 1996-2014), combination DMARDs (1% to 41%) and biologic (0 to 32%). Mean DAS28 fell (5.2 to 3.7), active disease (DAS28 > 5.1) declined (50% to 18%) and DAS28 remission (DAS28 < 2.6) increased (8% to 28%). In contrast HAQ scores were unchanged (1.30 to 1.32) and correlations between DAS28 and HAQ weakened (Spearman's rho fell from 0.56 to 0.44). CONCLUSIONS: Treatment intensity has increased over time, disease activity has fallen and there are more remissions. However, these improvements in controlling synovitis have not resulted in comparable reductions in disability measured by HAQ. As a consequence the relationship between DAS28 and HAQ has become weaker over time. Although the reasons for this divergence between disease activity and disability are uncertain, focussing treatment entirely in suppressing synovitis may be insufficient. PMID- 26818466 TI - Cerebellar ataxia and severe muscle CoQ10 deficiency in a patient with a novel mutation in ADCK3. AB - Inherited ataxias are a group of heterogeneous disorders in children or adults but their genetic definition remains still undetermined in almost half of the patients. However, CoQ10 deficiency is a rare cause of cerebellar ataxia and ADCK3 is the most frequent gene associated with this defect. We herein report a 48 year old man, who presented with dysarthria and walking difficulties. Brain magnetic resonance imaging showed a marked cerebellar atrophy. Serum lactate was elevated. Tissues obtained by muscle and skin biopsies were studied for biochemical and genetic characterization. Skeletal muscle biochemistry revealed decreased activities of complexes I+III and II+III and a severe reduction of CoQ10 , while skin fibroblasts showed normal CoQ10 levels. A mild loss of maximal respiration capacity was also found by high-resolution respirometry. Molecular studies identified a novel homozygous deletion (c.504del_CT) in ADCK3, causing a premature stop codon. Western blot analysis revealed marked reduction of ADCK3 protein levels. Treatment with CoQ10 was started and, after 1 year follow-up, patient neurological condition slightly improved. This report suggests the importance of investigating mitochondrial function and, in particular, muscle CoQ10 levels, in patients with adult-onset cerebellar ataxia. Moreover, clinical stabilization by CoQ10 supplementation emphasizes the importance of an early diagnosis. PMID- 26818467 TI - Host derived biomarkers of inflammation, apoptosis, and endothelial activation are associated with clinical outcomes in patients with bacteremia and sepsis regardless of microbial etiology. PMID- 26818468 TI - Comparison of the therapeutic efficacy and safety between tacrolimus and infliximab for moderate-to-severe ulcerative colitis: a single center experience. AB - OBJECTIVE: Both tacrolimus (Tac) and infliximab (IFX) are effective for moderate to-severe ulcerative colitis (UC). The aim of this study was to compare the therapeutic efficacy and safety of both drugs. MATERIALS AND METHODS: We performed a retrospective analysis of 46 patients with moderate-to-severe UC who were treated either by Tac (n = 21) or IFX (n = 25). We compared the remission and response rates for 10 weeks between the two groups. In patients who achieved a clinical response, the subsequent relapse rate was compared. The overall adverse events were also compared between the two groups. RESULTS: The remission and response rates at week 10 did not differ between patients treated with Tac (67% and 86%, respectively) and patients treated with IFX (76% and 92%, respectively). Among 41 patients showing a clinical response, eight of 23 patients treated with IFX and eight of 18 patients treated with Tac showed a subsequent relapse. The risk of relapse was not different between the two groups. While no serious adverse events were observed, the incidence of adverse events was higher in patients treated with Tac than in those treated with IFX. CONCLUSION: Tac and IFX may be equally efficacious for the induction and maintenance of remission in patients with UC while minor adverse events are more frequent with the former treatment. PMID- 26818469 TI - Efficacy of an Automated Multiple Emitter Whole-Room Ultraviolet-C Disinfection System Against Coronaviruses MHV and MERS-CoV. AB - Efficient and automated methods of disinfecting surfaces contaminated with the Middle Eastern respiratory syndrome coronavirus (MERS-CoV) may prevent the spread of the virus. Here we report the efficacy and use of an automated triple-emitter whole room UV-C disinfection system to inactivate mouse hepatitis virus, strain A59 (MHV-A59) and MERS-CoV viruses on surfaces with a >5 log10 reduction. PMID- 26818470 TI - Evaluation of the effect of silicone breast inserts on X-ray mammography and breast tomosynthesis images: A Monte Carlo simulation study. AB - PURPOSE: Breast augmentation is one of the most popular cosmetic surgeries worldwide. The aim of this study is to investigate the effect of breast implant insertion on the detectability and visibility of lesions on mammography and breast tomosynthesis (BT) images. MATERIALS AND METHODS: Three software phantoms, composed of a homogeneous background with embedded silicone gel structures, and two types of breast abnormalities, microcalcifications (uCs) and masses, were generated. Two X-ray breast imaging modalities were simulated: mammography and BT with six incident monochromatic X-ray beams with energies in the interval between 20 and 30 keV. Projection images were generated using an in-house developed Monte Carlo simulator. The detectability of mammographic findings adjacent to the implant material and the influence of the incident beam energy and implant thickness on the feature detection were studied. RESULTS: It was found that implants thicker than 26 mm for the case of mammography and 14 mm for the case of BT obscured the visibility of underlying structures. Although BT demonstrated a lack of contrast, this modality was able to visualize uCs under considerable depths of implant. Increasing the incident beam energy led to better visualization of small uCs, while in the case of breast masses, their detectability was limited. CONCLUSIONS: Silicone gel implants introduce a limitation in the image quality of mammograms resulting in low detectability of features. In addition, silicone gel implants obscure partially or totally parts of the image, depending on the size and the thickness of the implant as well the energy of the X-rays used. PMID- 26818471 TI - PET iterative reconstruction incorporating an efficient positron range correction method. AB - Positron range is one of the main physical effects limiting the spatial resolution of positron emission tomography (PET) images. If positrons travel inside a magnetic field, for instance inside a nuclear magnetic resonance (MR) tomograph, the mean range will be smaller but still significant. In this investigation we examined a method to correct for the positron range effect in iterative image reconstruction by including tissue-specific kernels in the forward projection operation. The correction method was implemented within STIR library (Software for Tomographic Image Reconstruction). In order to obtain the positron annihilation distribution of various radioactive isotopes in water and lung tissue, simulations were performed with the Monte Carlo package GATE [Jan et al. 2004 [1]] simulating different magnetic field intensities (0 T, 3 T, 9.5 T and 11 T) along the axial scanner direction. The positron range kernels were obtained for (68)Ga in water and lung tissue for 0 T and 3 T magnetic field voxellizing the annihilation coordinates into a three-dimensional matrix. The proposed method was evaluated using simulations of material-variant and material invariant positron range corrections for the HYPERImage preclinical PET-MR scanner. The use of the correction resulted in sharper active region boundary definition, albeit with noise enhancement, and in the recovery of the true activity mean value of the hot regions. Moreover, in the case where a magnetic field is present, the correction accounts for the non-isotropy of the positron range effect, resulting in the recovery of resolution along the axial plane. PMID- 26818472 TI - Non-thermal plasma inhibits human cervical cancer HeLa cells invasiveness by suppressing the MAPK pathway and decreasing matrix metalloproteinase-9 expression. AB - Non-thermal plasma (NTP) has been proposed as a novel therapeutic method for anticancer treatment. However, the mechanism underlying its biological effects remains unclear. In this study, we investigated the inhibitory effect of NTP on the invasion of HeLa cells, and explored the possible mechanism. Our results showed that NTP exposure for 20 or 40 s significantly suppressed the migration and invasion of HeLa cells on the basis of matrigel invasion assay and wound healing assay, respectively. Moreover, NTP reduced the activity and protein expression of the matrix metalloproteinase (MMP)-9 enzyme. Western blot analysis indicated that NTP exposure effectively decreased phosphorylation level of both ERK1/2 and JNK, but not p38 MAPK. Furthermore, treatment with MAPK signal pathway inhibitors or NTP all exhibited significant depression of HeLa cells migration and MMP-9 expression. The result showed that NTP synergistically suppressed migration and MMP-9 expression in the presence of ERK1/2 inhibitor and JNK inhibitor, but not p38 MAPK inhibitor. Taken together, these findings suggested that NTP exposure inhibited the migration and invasion of HeLa cells via down regulating MMP-9 expression in ERK1/2 and JNK signaling pathways dependent manner. These findings provide hints to the potential clinical research and therapy of NTP on cervical cancer metastasis. PMID- 26818473 TI - Association of Rosacea With Risk for Glioma in a Danish Nationwide Cohort Study. AB - IMPORTANCE: Rosacea, a common facial skin disorder, has a poorly understood pathogenesis in which increased matrix metalloproteinase activity might play an important role. Glioma accounts for 80% of all primary malignant tumors in the central nervous system, and these tumors also show upregulation of certain matrix metalloproteinases. OBJECTIVE: To investigate the association between rosacea and the risk for glioma. DESIGN, SETTING, AND PARTICIPANTS: Nationwide cohort study of the Danish population from individual-level linkage of administrative registers. All Danish citizens 18 years or older from January 1, 1997, to December 31, 2011, were eligible for inclusion. A total of 5 484 910 individuals were eligible for analysis; of these, 68 372 had rosacea and 5 416 538 constituted the reference population. Data were analyzed from July 14 to August 10, 2015. MAIN OUTCOMES AND MEASURES: The outcome of interest was a diagnosis of glioma. Incidence rates per 10 000 person-years were calculated, and incidence rate ratios adjusted for age, sex, and socioeconomic status were estimated by Poisson regression distribution models. RESULTS: Of the 5 484 910 individuals in the study population, 21 118 individuals developed glioma during the study period, including 20 934 of the 5 416 538 individuals in the reference population (50.4% women; mean [SD] age, 40.8 [19.7] years) and 184 of the 68 372 patients with rosacea (67.3% women; mean [SD] age, 42.2 [16.5] years). The incidence rate (95% CI) of glioma was 3.34 (3.30-3.39) in the reference population and 4.99 (4.32-5.76) in patients with rosacea. The adjusted incidence rate ratio (95% CI) of glioma in patients with rosacea was 1.36 (1.18-1.58) in our primary analysis. When analyses were limited to patients with a primary diagnosis of rosacea by a hospital dermatologist (n = 5964), the adjusted incidence rate ratio was 1.82 (1.16-2.86). CONCLUSIONS AND RELEVANCE: Rosacea was associated with a significantly increased risk for glioma in a nationwide cohort. This association may be mediated, in part, by mechanisms dependent on matrix metalloproteinases. Increased focus on neurologic symptoms in patients with rosacea may be warranted. PMID- 26818475 TI - Polymorphisms and haplotype of ROCK2 associate with high altitude essential hypertension in native high altitude Ladakhi Indian population: a preliminary study. AB - BACKGROUND AND OBJECTIVES: High-altitude essential hypertension (HAEH) is a disease occurring in permanent residents of high-altitude regions. The disease is characterized with SBP >=140 mmHg and DBP >=90 mmHg. HAEH is known to run in families, i.e. the disease has genetic component. Rho-associated coiled-coil containing protein kinase 2 (ROCK2) is a stress-activated serine-threonine kinase known to disturb vascular-homeostasis leading to an increase in systemic vascular resistance, hallmark of HAEH. ROCK2 is implicated in sea-level essential hypertension but its role in HAEH is yet to be elucidated. METHODS: The present study deals with genotyping 13 polymorphisms of ROCK2 gene in demographicaly matched human cases (n = 65) and controls (n = 38) by Sequenom MS (TOF)-based MassARRAY platform using iPLEX Gold technology. RESULTS: A significant association was observed for GG genotype (SNP, rs978906), AA genotype (SNP, rs6753921), GG genotype (SNP, rs10495582) and AA genotype (SNP, rs2230774) with HAEH (p < 0.05). The 4 SNPs were tagged to each other and formed a 35 kb LD block (r(2 )> 0.90). Haplotype AGCC, composed of wild-type alleles of the SNPs was over represented in controls. In contrast, haplotype GAGA, composed of variant-alleles was observed to be in higher proportion in cases. Moreover, SBP levels (mmHg) were higher in cases with risk genotype against the ones having protective genotype (p = 0.05). Bioinformatic analysis revealed binding of a critical transcription factor, SRF to variant-allele G of SNP rs10495582. SRF has been reported in previous studies to promote ROCK2 transcriptional expression. INTERPRETATION AND CONCLUSIONS: The data clearly suggests association of ROCK2 polymorphisms and haplotypes with HAEH. PMID- 26818474 TI - Management of patients with issues related to opioid safety, efficacy and/or misuse: a case series from an integrated, interdisciplinary clinic. AB - BACKGROUND: Patients, providers, communities and health systems have struggled to achieve balance between access to opioid treatment for chronic pain and its potential harmful consequences: especially misuse, addiction and overdose. We developed an interdisciplinary clinic embedded within primary care (the Opioid Reassessment Clinic-ORC) with the goal of improving the quality of care of patients with co-occurring chronic pain and issues related to opioid safety, efficacy and/or misuse. CASE DESCRIPTIONS: We present three cases referred to the ORC that highlight complex clinical scenarios related to assessment and treatment of patients with chronic pain and issues related to opioid safety, efficacy and misuse. DISCUSSION AND EVALUATION: In the context of the three cases, with respect to assessment, we discuss: making the diagnosis of opioid use disorder; allowing the patient space to endorse lack of efficacy; identification of co occurring hazardous alcohol use; and recognizing barriers to multimodal pain care. With respect to treatment, we discuss: making a change in treatment with which the patient may not agree; effectiveness of buprenorphine/naloxone for the treatment of chronic pain; responding to low efficacy; and making continued opioid therapy contingent on engagement with substance abuse treatment. CONCLUSIONS: The core components of our approach-biopsychosocial assessment and multimodal treatment planning with an emphasis on promoting functional goals and safety using clear communication and a patient-centered stance-should guide providers in the management of similar clinical scenarios. More evidence is needed to definitively guide specific interventions and points of clinical equipoise. PMID- 26818476 TI - Diagnostic and Therapeutic Challenges. PMID- 26818477 TI - MACULAR BRUCH MEMBRANE DEFECTS IN HIGHLY MYOPIC EYES: The Beijing Eye Study. AB - PURPOSE: To examine prevalence and associations of macular Bruch membrane defects (MBMDs) in a population-based setting. DESIGN: Population-based cross-sectional study. METHODS: The Beijing Eye Study 2011 included 3,468 subjects who underwent a detailed ophthalmic examination including spectral domain optical coherence tomography with enhanced depth imaging of the macula. Macular Bruch membrane defects were defined as an interruption of Bruch membrane on the optical coherence tomography images in the macular region. RESULTS: Macular Bruch membrane defects could be detected only in highly myopic eyes (defined as refractive error of <=-6 diopters or axial length of >=26.5 mm) with a prevalence of 17/164 (10.4%, 95% confidence interval [CI], 5.7%-18.1%). Best-corrected visual acuity <0.05 was found in 5 (29%) of 17 eyes with MBMDs, and in 7 (41%) eyes, visual acuity was <0.3 and >=0.05. In the MBMD region, retinal pigment epithelium and choriocapillaris were completely lost, and the deep and middle layers of the retina and the choroid were almost completely absent. In the MBMD region, mean retinal thickness was 153 +/- 57 MUm (mean +/- SD) and choroidal thickness was 12.7 +/- 28.1 MUm. On the fundus photographs, MBMDs appeared as whitish areas with round borders. In multivariate regression analysis, presence of MBMD was significantly associated only with longer axial length (Odds ratio: 3.87; 95% CI, 1.64-9.14). CONCLUSION: Macular Bruch membrane defects with a prevalence of approximately 10% in highly myopic eyes are associated with a complete loss of retinal pigment epithelium and choriocapillaris, an almost complete loss of photoreceptors and choroid, and marked reduction in visual acuity. Macular Bruch membrane defects may be added to the panoply of features of myopic maculopathy. PMID- 26818478 TI - DIAGNOSTIC ACCURACY EVALUATION OF VISUAL ACUITY AND FUNDUS AUTOFLUORESCENCE MACULAR GEOGRAPHIC ATROPHY AREA FOR THE DISCRIMINATION OF STARGARDT GROUPS. AB - PURPOSE: To evaluate diagnostic accuracy of visual acuity and fundus autofluorescence (FAF) macular geographic atrophy (GA) area for the discrimination of autosomal recessive Stargardt groups. METHODS: Subjects aged <50 years old with confirmed molecular diagnoses were classified to Groups 1, 2, or 3 according to a full-field electroretinogram reference standard. Diagnostic accuracy of visual acuity and the FAF macular GA area was assessed with generalized estimating equations, receiver operating characteristic curve area under the curve, and support vector machines. RESULTS: Ten eyes were classified as Group 1 and 7 as Group 2. The mean log minimum angle resolution (Snellen equivalent) was 0.64 (20/87) for group 1 and 0.96 (20/182) for group 2. Mean FAF macular GA area was 0.96 mm for Group 1 and 3.23 mm for Group 2. The generalized estimating equation analysis showed an 8.3% increase in odds of Group 2 classification with each 0.1-unit increase in log minimum angle resolution and a 24% increase with each 1-mm increase in FAF macular GA area. Multivariate generalized estimating equation analysis showed that only the FAF macular GA area was significant. Area under the curve was 0.79 for log minimum angle resolution and 0.89 for FAF macular GA area. The support vector machine classification accuracy was 71% for log minimum angle resolution and 82% for FAF macular GA area. CONCLUSION: Visual acuity and FAF macular GA area had good independent accuracy for the discrimination of groups 1 and 2, indicating that they may serve as useful diagnostic parameters. PMID- 26818479 TI - Sequential Optical Coherence Tomography Images of Early Macular Necrosis Caused by Acute Retinal Necrosis in Non-Human Immunodeficiency Virus Patients. PMID- 26818480 TI - LONGITUDINAL QUANTITATIVE EVALUATION OF PHOTORECEPTOR VOLUME FOLLOWING REPAIR OF MACULA-OFF RETINAL DETACHMENT. AB - PURPOSE: To quantify photoreceptor volume changes after successful surgical repair of macula-off retinal detachment and to correlate these volumetric changes to postoperative best-corrected visual acuity (BCVA). METHODS: Retrospective study of 15 eyes of 15 patients with macula-off retinal detachment who underwent successful surgical repair. A minimum of 4 optical coherence tomography scans that straddled the foveal center was used to quantify the central photoreceptor volume (central 1 mm). RESULTS: Mean photoreceptor volume at the first postoperative visit was 0.451 mm, increasing to 0.523 mm at the final postoperative visit (P = 0.004). Mean BCVA improved from 1.13 +/- 0.59 logarithm of the minimum angle of resolution units (~20/270) preoperatively to 0.52 +/- 0.42 logarithm of the minimum angle of resolution units (~20/66) at the final postoperative visit (P = 0.001). Mean photoreceptor volume at either the initial or final visit demonstrated significant correlations with final postoperative BCVA (r = -0.670, P = 0.017 and r = -0.753, P = 0.005, respectively). Shorter time interval from diagnosis to surgery was significantly associated with greater mean final postoperative photoreceptor volume (r = -0.588, P = 0.021) and better mean final postoperative BCVA (r = 0.709, P = 0.003). CONCLUSION: We observed a significant increase in photoreceptor volume after successful retinal detachment repair; photoreceptor volume was positively associated with BCVA and time to surgery. Our series emphasizes the importance of prompt surgical repair and shows that photoreceptor recovery and volumetric improvement correlate significantly with BCVA. PMID- 26818481 TI - Phylogenomics at the tips: inferring lineages and their demographic history in a tropical lizard, Carlia amax. AB - High-throughput sequencing approaches offer opportunities to better understand the evolutionary processes driving diversification, particularly in nonmodel organisms. In particular, the 100-1000's of loci that can now be sequenced are providing unprecedented power in population, speciation and phylogenetic studies. Here, we apply an exon capture approach to generate >99% complete sequence and SNP data across >2000 loci from a tropical skink, Carlia amax, and exploit these data to identify divergent lineages and infer their relationships and demographic histories. This is especially relevant to low-dispersal tropical taxa that often have cryptic diversity and spatially dynamic histories. For C. amax, clustering of nuclear SNPs and coalescent-based species delimitation analyses identify four divergent lineages, one fewer than predicted based on geographically coherent mtDNA clades (>9.4% sequence divergence). Three of these lineages are widespread and parapatric on the mainland, whereas the most divergent is restricted to islands off the northeast Northern Territory. Tests for population expansion reject an equilibrium isolation-by-distance model for two of the three widespread lineages and infer refugial expansion sources in the relatively mesic northeast Top End and northwest Kimberley. The latter is already recognized as a hotspot of endemism, but our results also suggest that a stronger focus on the northeast Top End, and adjacent islands is warranted. More generally, our results show how genome-reduction methods such as exon capture can yield insights into the pattern and dynamics of biodiversity across complex landscapes with as yet poorly understood biogeographic history and how exon data can link between population and phylogenetic questions. PMID- 26818482 TI - Morbidly Obese Patients Exhibit Increased CYP2E1-Mediated Oxidation of Acetaminophen. AB - INTRODUCTION: Acetaminophen (paracetamol) is mainly metabolized via glucuronidation and sulphation, while the minor pathway through cytochrome P450 (CYP) 2E1 is held responsible for hepatotoxicity. In obese patients, CYP2E1 activity is reported to be induced, thereby potentially worsening the safety profile of acetaminophen. The aim of this study was to determine the pharmacokinetics of acetaminophen and its metabolites (glucuronide, sulphate, cysteine and mercapturate) in morbidly obese and non-obese patients. METHODS: Twenty morbidly obese patients (with a median total body weight [TBW] of 140.1 kg [range 106-193.1 kg] and body mass index [BMI] of 45.1 kg/m(2) [40-55.2 kg/m(2)]) and eight non-obese patients (with a TBW of 69.4 kg [53.4-91.7] and BMI of 21.8 kg/m(2) [19.4-27.4]) received 2 g of intravenous acetaminophen. Fifteen blood samples were collected per patient. Population pharmacokinetic modelling was performed using NONMEM. RESULTS: In morbidly obese patients, the median area under the plasma concentration-time curve from 0 to 8 h (AUC0-8h) of acetaminophen was significantly smaller (P = 0.009), while the AUC0-8h ratios of the glucuronide, sulphate and cysteine metabolites to acetaminophen were significantly higher (P = 0.043, 0.004 and 0.010, respectively). In the model, acetaminophen CYP2E1-mediated clearance (cysteine and mercapturate) increased with lean body weight [LBW] (population mean [relative standard error] 0.0185 L/min [15 %], P < 0.01). Moreover, accelerated formation of the cysteine and mercapturate metabolites was found with increasing LBW (P < 0.001). Glucuronidation clearance (0.219 L/min [5 %]) and sulphation clearance (0.0646 L/min [6 %]) also increased with LBW (P < 0.001). CONCLUSION: Obesity leads to lower acetaminophen concentrations and earlier and higher peak concentrations of acetaminophen cysteine and mercapturate. While a higher dose may be anticipated to achieve adequate acetaminophen concentrations, the increased CYP2E1-mediated pathway may preclude this dose adjustment. PMID- 26818484 TI - Improving delivery of secondary prophylaxis for rheumatic heart disease in remote Indigenous communities: study protocol for a stepped-wedge randomised trial. AB - BACKGROUND: Rheumatic heart disease (RHD), caused by acute rheumatic fever (ARF), is a major health problem in Australian Aboriginal communities. Progress in controlling RHD requires improvements in the delivery of secondary prophylaxis, which comprises regular, long-term injections of penicillin for people with ARF/RHD. METHODS/DESIGN: This trial aims to improve uptake of secondary prophylaxis among Aboriginal people with ARF/RHD to reduce progression or worsening of RHD. This is a stepped-wedge, randomised trial in consenting communities in Australia's Northern Territory. Pairs of randomly-chosen clinics from among those consenting enter the study at 3-monthly steps. The intervention to which clinics are randomised comprises a multi-faceted systems-based package, in which clinics are supported to develop and implement strategies to improve penicillin delivery, aligned with elements of the Chronic Care Model. Continuous quality improvement processes will be used, including 3-monthly feedback to clinic staff of adherence rates of their ARF/RHD clients. The primary outcome is the proportion of people with ARF/RHD receiving >= 80% of scheduled penicillin injections over a minimum 12-month period. The sample size of 300 ARF/RHD clients across five community clusters will power the study to detect a 20% increase in the proportion of individuals achieving this target, from a worrying low baseline of 20%, to 40 %. Secondary outcomes pertaining to other measures of adherence will be assessed. Within the randomised trial design, a mixed-methods evaluation will be embedded to evaluate the efficiency, effectiveness, impact and relevance, sustainability, process and fidelity, and performance of the intervention. The evaluation will establish any causal link between outcomes and the intervention. The planned study duration is from 2013 to 2016. DISCUSSION: Continuous quality improvement has a strong track record in Australia's Northern Territory, and its use has resulted in modest benefits in a pilot, non-randomised ARF/RHD study. If successful, this new intervention using the Chronic Care Model as a scaffold and evaluated using a well-developed theory-based framework, will provide a practical and transferable approach to ARF/RHD control. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613000223730. Date registered: 25 February 2013. PMID- 26818483 TI - Potential Sources of Inter-Subject Variability in Monoclonal Antibody Pharmacokinetics. AB - Understanding inter-subject variability in drug pharmacokinetics and pharmacodynamics is important to ensure that all patients attain suitable drug exposure to achieve efficacy and avoid toxicity. Inter-subject variability in the pharmacokinetics of therapeutic monoclonal antibodies (mAbs) is generally moderate to high; however, the factors responsible for the high inter-subject variability have not been comprehensively reviewed. In this review, the extent of inter-subject variability for mAb pharmacokinetics is presented and potential factors contributing to this variability are explored and summarised. Disease status, age, sex, ethnicity, body size, genetic polymorphisms, concomitant medication, co-morbidities, immune status and multiple other patient-specific details have been considered. The inter-subject variability for mAb pharmacokinetics most likely depends on the complex interplay of multiple factors. However, studies aimed at investigating the reasons for the inter subject variability are sparse. Population pharmacokinetic models and physiologically based pharmacokinetic models are useful tools to identify important covariates, aiding in the understanding of factors contributing to inter-subject variability. Further understanding of inter-subject variability in pharmacokinetics should aid in development of dosing regimens that are more appropriate. PMID- 26818486 TI - Arterial Thickness and Immunometabolism: The Mediating role of Chronic Exercise. AB - Metabolic alterations and cardiovascular diseases, such as atherosclerosis, are associated with lifestyle modifications, particularly the increase of physical inactivity and poor eating habits, which contribute to one of the main causes of death in modern times. Cardiovascular diseases are positively correlated with several illnesses, such as obesity, hypertension and dyslipidemia, and these disorders are known to contribute to changes in immune cells, cytokines and metabolism. Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid plaques and fibrous tissue (atheroma) in the artery walls and this process is related to the oxidation of LDL-c (low density lipoprotein) and the formation of a particle, termed LDLox, which can generate toxic injury to the vessel wall. In this atherogenic process there is an inflammatory response generated by the injury in the vascular endothelium, which in itself is able to express and secrete a variety of molecules, such as myeloid colony-stimulating factors (M-CSF), monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor alpha (TNF-alpha), that act as activators of the immune system. Therefore, the main purpose of this review is to highlight the immuno-metabolic alterations involving the thickening and stiffness of arteries observed in atherosclerosis, and how chronic exercise can act as an anti-inflammatory and anti-atherogenic approach. PMID- 26818485 TI - The Impact of Opioids on Cardiac Electrophysiology. AB - Synthetic opioid agents have been used in modern medicine for over a century and for opioid addiction treatment for over a half-century. Liberal use of opioids in the United States has been attended by an extraordinary increase in opioid related mortality, with over 16,000 deaths in 2012. As there have been advances in opioid agents for pain and addiction, so have there been advances in our understanding of the cardiac effects of these agents. In the last 10 years, significant data regarding electrophysiologic effects of these agents have been collected. We aim in this review to discuss the effects on cardiac electrophysiology of the various opioid agents currently in use and the evidence that these effects are contributing to the rise in opioid-related mortality. PMID- 26818487 TI - Drug Therapy for Hypertrophic Cardiomypathy: Physiology and Practice. AB - HCM is the most common inherited heart condition occurring in 1:500 individuals in the general population. Left ventricular outflow obstruction at rest or after provocation occurs in 2/3 of HCM patients and is a frequent cause of limiting symptoms. Pharmacologic therapy is the first-line treatment for obstruction, and should be aggressively pursued before application of invasive therapy. Beta blockade is given first, and up-titrated to decrease resting heart rate to between 50 and 60 beats per minute. However, beta-blockade is not expected to decrease resting gradients; its effect rests on decreasing the rise in gradient that accompanies exercise. For patients who fail beta-blockade the addition of oral disopyramide in adequate dose often will decrease resting gradients and offer meaningful relief of symptoms. Disopyramide vagolytic side effects, if they occur, can be greatly mitigated by simultaneous administration of oral pyridostigmine. This combination allows adequate dosing of disopyramide to achieve therapeutic goals. Verapamil utility in obstructive HCM with high resting gradients is limited by its vasodilating effects that can, infrequently, worsen gradient and symptoms. As such, we tend to avoid it in patients with high gradients and limiting heart failure symptoms. In a head-to-head comparison of intravenous drug administration in individual obstructive HCM patients the relative efficacy for lowering gradient was disopyramide > beta-blockade > verapamil. Severe symptoms in non-obstructive HCM are caused by fibrosis or severe myocyte disarray, and often by very small LV chamber size. Severe symptoms caused by these anatomic and histologic abnormalities, in the absence of obstruction, are less amenable to current pharmacotherapy. New pharmacotherapeutic approaches to HCM are on the horizon, that are to be evaluated in formal therapeutic trials. PMID- 26818489 TI - Racial and Ethnic Disparities in Outpatient Substance Use Disorder Treatment Episode Completion for Different Substances. AB - This study investigates how racial and ethnic disparities in treatment episode completion vary across different problem substances in an urban sample of 416,224 outpatient treatment discharges drawn from the 2011 U.S. Treatment Episode Dataset-Discharge (TEDS-D) data set. Fixed effects logistic regression is employed to test for the association of race and ethnicity with treatment episode completion for different substances of use while controlling for confounding demographic, socioeconomic, and geographic clustering factors. Results show that African Americans and Hispanics are less likely to complete a treatment episode than Whites, and that these disparities vary among users of different substances. For African Americans, this disparity is observed over all substances, but is particularly acute among users of alcohol and methamphetamine, substances for which African Americans generally have lower rates of use disorder as compared to Whites. For Hispanics, this disparity is driven primarily by users of heroin, for which Hispanics are only 75% as likely as Whites to complete a treatment episode. For users of cocaine and methamphetamine, there is no significant difference between Hispanics and Whites in the likelihood of treatment episode completion. These results contribute to emerging research on the mechanisms of substance use disorder treatment outcomes and highlight the need for culturally appropriate treatment programs to enhance treatment program retention and associated positive post-treatment outcomes. PMID- 26818490 TI - Drug eruption due to entecavir: A case report and mini-review. PMID- 26818488 TI - Bioresorbable Scaffolds for Atheroregression: Understanding of Transient Scaffolding. AB - This review focuses on the clinical and biological features of the bioresorbable scaffolds in interventional cardiology highlighting scientific achievements and challenges of the transient scaffolding with Absorb BVS. Special attention is granted to the vascular biology pathways which, involved in the resorption of scaffold, artery remodeling and mechanisms of Glagovian atheroregression setting the stage for subsequent clinical applications. Twenty five years ago Glagov described the phenomenon of limited external elastic membrane enlargement in response to an increase in plaque burden. We believe this threshold becomes the target for development of strategies that reverse atherosclerosis, and particularly transient scaffolding has a potential to be a tool to ultimately conquer atherosclerosis. PMID- 26818491 TI - Huichol Migrant Laborers and Pesticides: Structural Violence and Cultural Confounders. AB - Every year, around two thousand Huichol families migrate from their homelands in the highlands of northwestern Mexico to the coastal region of Nayarit State, where they are employed on small plantations to pick and thread tobacco leaves. During their four-month stay, they live, work, eat, and sleep in the open air next to the tobacco fields, exposing themselves to an unknown cocktail of pesticides all day, every day. In this article, I describe how these indigenous migrants are more at risk to pesticides because historical and contemporary structural factors ensure that they live and work in the way of harm. I discuss the economic, social, political, and racial inequalities that exist in their every-day environment and how these forms of structural violence are mitigated by their intersection with local cultural contexts and their specific indigenous lifeworld. PMID- 26818492 TI - How attitude strength and information influence moral decision making: Evidence from event-related potentials. AB - Moral judgments are based on complex processing. This study aimed to investigate neural correlates of moral decisions. Participants (N = 32) were asked to express their opinion on various moral issues while ERPs were recorded. After reading texts containing either confirming or contradicting arguments regarding the issues, participants were asked to express their opinion again. A higher N400 amplitude and a higher amplitude of the late positive potential for value incongruent words compared to value-congruent words could be observed. Furthermore, after participants had read conflicting arguments, slower responses and larger N400 differences (value-incongruent minus value-congruent) were observed. These results showed that language processing for a moral context is influenced by the subjective value system, and it can be assumed that a demanding cognitive elaboration contributed to the observed RT and N400 priming effects. This is the first ERP study comparing moral judgments before and after reading confirming or conflicting information; it revealed that evaluative reasoning can influence neural processing for moral decisions. PMID- 26818493 TI - Do fewer males present to clinical high-risk services for psychosis relative to first-episode services? AB - AIM: A decline in the rate of transition to psychosis in patients presenting with clinical high-risk has been reported in the literature. Several hypotheses have been put forward to explain this decline. In this brief report, we aimed to explore whether the demographic group presenting to clinical high-risk services differs from the 'end-point' population who present with first-episode psychosis (FEP), by focusing on gender. METHOD: Gender distribution was compared between clinical high-risk (CHR) and FEP using data extracted from published study samples and clinical data from corresponding cohorts within the same catchment area in South London. RESULTS: The proportion of males was significantly higher in FEP compared to CHR services in the literature describing Europe, Australia and North America and in the clinical cohort from South London. CONCLUSION: Males are under-represented in existing CHR services in Europe, Australia and North America. This could reflect less willingness in males to seek help if experiencing low-level psychological distress and may be related to the declining transition. PMID- 26818494 TI - Racial diversity in mortality and morbidity in urban patients with hepatitis C. AB - Defining mortality for Caucasians and African American patients with chronic hepatitis C with respect to racial diversity is critical for counselling patients on therapy options. The objective of this study was to define racial diversity influence on mortality and morbidity of 3724 consecutive hepatitis C virus (HCV) infected patients seen in an urban clinic between 1995 and 2008. Mortality, as of 2011, was defined using the SSA National Death Index and correlated with early visit medical information. The HCV chronically infected patient population consisted of 2879 African Americans (AA), 758 Caucasians and 87 other, and the majority were not treated for their infection prior to 2011. The average time to death from first visit was 5 years, the average age at death was 55 years, and despite racial diversity, AA were just as likely to be reported dead as Caucasians (23% AA vs 22% Caucasians). Cirrhosis and fibrosis (liver biopsy, AST Platelet Ratio Index or Fibrosis-4) at first visit as well as low albumin, diabetes, renal impairment and cardiac symptoms were associated with increased mortality. Treated patients who cleared the virus (sustained viral response (SVR); AA = 59; Caucasians = 40) had lower mortality than patients who were not treated (AA: 5% vs 27%; Caucasians 5% vs 26%). Hence, we find that race is not a factor in the early mortality of patients with chronic HCV infection and achieving a SVR reduced mortality. Unexpectedly, nonresponding AA also benefited by a lower mortality. African American patients with kidney disease and low albumin were at highest risk and should be treated as soon as identified. PMID- 26818495 TI - Diaschisis: An Old Concept Brought to New Life. PMID- 26818496 TI - Integrated Stress Response: Connecting ApoE4 to Memory Impairment in Alzheimer's Disease. PMID- 26818497 TI - Why Don't We Move Slower? The Value of Time in the Neural Control of Action. AB - To want something now rather than later is a common attitude that reflects the brain's tendency to value the passage of time. Because the time taken to accomplish an action inevitably delays task achievement and reward acquisition, this idea was ported to neural movement control within the "cost of time" theory. This theory provides a normative framework to account for the underpinnings of movement time formation within the brain and the origin of a self-selected pace in human and animal motion. Then, how does the brain exactly value time in the control of action? To tackle this issue, we used an inverse optimal control approach and developed a general methodology allowing to squarely sample infinitesimal values of the time cost from experimental motion data. The cost of time underlying saccades was found to have a concave growth, thereby confirming previous results on hyperbolic reward discounting, yet without making any prior assumption about this hypothetical nature. For self-paced reaching, however, movement time was primarily valued according to a striking sigmoidal shape; its rate of change consistently presented a steep rise before a maximum was reached and a slower decay was observed. Theoretical properties of uniqueness and robustness of the inferred time cost were established for the class of problems under investigation, thus reinforcing the significance of the present findings. These results may offer a unique opportunity to uncover how the brain values the passage of time in healthy and pathological motor control and shed new light on the processes underlying action invigoration. SIGNIFICANCE STATEMENT: Movement time is a fundamental characteristic of neural motor control, but the principles underlying its formation remain little known. This work addresses that question within the inverse optimal control framework where the challenge is to uncover what optimality criterion underlies a system's behavior. Here we rely on the "cost of time" theory that finds its roots into the brain's tendency to discount the actual value of future reward. It asserts that the time elapsed until action completion entails a cost, thereby making slow moves nonoptimal. By means of a thorough theoretical analysis, the present article shows how to sample the infinitesimal values of the time cost without prior assumption about its hypothetical nature and emphasizes its sigmoidal shape for reaching. PMID- 26818498 TI - Dendrites In Vitro and In Vivo Contain Microtubules of Opposite Polarity and Axon Formation Correlates with Uniform Plus-End-Out Microtubule Orientation. AB - In cultured vertebrate neurons, axons have a uniform arrangement of microtubules with plus-ends distal to the cell body (plus-end-out), whereas dendrites contain mixed polarity orientations with both plus-end-out and minus-end-out oriented microtubules. Rather than non-uniform microtubules, uniparallel minus-end-out microtubules are the signature of dendrites in Drosophila and Caenorhabditis elegans neurons. To determine whether mixed microtubule organization is a conserved feature of vertebrate dendrites, we used live-cell imaging to systematically analyze microtubule plus-end orientations in primary cultures of rat hippocampal and cortical neurons, dentate granule cells in mouse organotypic slices, and layer 2/3 pyramidal neurons in the somatosensory cortex of living mice. In vitro and in vivo, all microtubules had a plus-end-out orientation in axons, whereas microtubules in dendrites had mixed orientations. When dendritic microtubules were severed by laser-based microsurgery, we detected equal numbers of plus- and minus-end-out microtubule orientations throughout the dendritic processes. In dendrites, the minus-end-out microtubules were generally more stable and comparable with plus-end-out microtubules in axons. Interestingly, at early stages of neuronal development in nonpolarized cells, newly formed neurites already contained microtubules of opposite polarity, suggesting that the establishment of uniform plus-end-out microtubules occurs during axon formation. We propose a model in which the selective formation of uniform plus-end-out microtubules in the axon is a critical process underlying neuronal polarization. SIGNIFICANCE STATEMENT: Live-cell imaging was used to systematically analyze microtubule organization in primary cultures of rat hippocampal neurons, dentate granule cells in mouse organotypic slices, and layer 2/3 pyramidal neuron in somatosensory cortex of living mice. In vitro and in vivo, all microtubules have a plus-end-out orientation in axons, whereas microtubules in dendrites have mixed orientations. Interestingly, newly formed neurites of nonpolarized neurons already contain mixed microtubules, and the specific organization of uniform plus end-out microtubules only occurs during axon formation. Based on these findings, the authors propose a model in which the selective formation of uniform plus-end out microtubules in the axon is a critical process underlying neuronal polarization. PMID- 26818499 TI - Regulation of ATP13A2 via PHD2-HIF1alpha Signaling Is Critical for Cellular Iron Homeostasis: Implications for Parkinson's Disease. AB - We previously reported that pharmacological inhibition of a class of enzymes known as prolyl hydroxylase domain proteins (PHDs) has neuroprotective effects in various in vitro and in vivo models of Parkinson's disease (PD). We hypothesized that this was due to inhibition of the PHD2 isoform, preventing it from hydroxylating the transcription factor hypoxia inducible factor 1 alpha (HIF1alpha), targeting it for eventual proteasomal degradation. HIF1alpha itself induces the transcription of various cellular stress genes, including several involved in iron metabolism. Although all three isoforms of PHD are expressed within vulnerable dopaminergic (DAergic) substantia nigra pars compacta neurons, only select downregulation of the PHD2 isoform was found to protect against in vivo neurodegenerative effects associated with the mitochondrial neurotoxin 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine. These findings were corroborated in induced pluripotent stem cell-derived neurons, providing validation in a pertinent human cell model. PHD2 inhibition was found to result in increased expression of ATP13A2, mutation of which is responsible for a rare juvenile form of PD known as Kufor-Rakeb syndrome. Knockdown of ATP13A2 expression within human DAergic cells was found to abrogate restoration of cellular iron homeostasis and neuronal cell viability elicited by inhibition of PHD2 under conditions of mitochondrial stress, likely via effects on lysosomal iron storage. These data suggest that regulation of ATP13A2 by the PHD2-HIF1alpha signaling pathway affects cellular iron homeostasis and DAergic neuronal survival. This constitutes a heretofore unrecognized process associated with loss of ATP13A2 function that could have wide-ranging implications for it as a therapeutic target for PD and other related conditions. SIGNIFICANCE STATEMENT: Reductions in PHD2 activity within dopaminergic neurons in vivo and in cultured human induced pluripotent stem cell-derived neurons protects against mitochondrial stress-induced neurotoxicity. Protective effects are dependent on downstream HIF-1alpha expression. Knockdown of ATP13A2, a gene linked to a rare juvenile form of Parkinson's disease and recently identified as a novel HIF1alpha target, was found to abrogate maintenance of cellular iron homeostasis and neuronal viability elicited by PHD2 inhibition in vivo and in cultured dopaminergic cells under conditions of mitochondrial stress. Mechanistically, this was due to ATP13A2's role in maintaining lysosomal iron stores. This constitutes a novel mechanism by which alterations in ATP13A2 activity may be driving PD-related neuropathology. PMID- 26818500 TI - Neural Mechanisms of Credit Assignment in a Multicue Environment. AB - In complex environments, many potential cues can guide a decision or be assigned responsibility for the outcome of the decision. We know little, however, about how humans and animals select relevant information sources that should guide behavior. We show that subjects solve this relevance selection and credit assignment problem by selecting one cue and its association with a particular outcome as the main focus of a hypothesis. To do this, we examined learning while using a task design that allowed us to estimate the focus of each subject's hypotheses on a trial-by-trial basis. When a prediction is confirmed by the outcome, then credit for the outcome is assigned to that cue rather than an alternative. Activity in medial frontal cortex is associated with the assignment of credit to the cue that is the main focus of the hypothesis. However, when the outcome disconfirms a prediction, the focus shifts between cues, and the credit for the outcome is assigned to an alternative cue. This process of reselection for credit assignment to an alternative cue is associated with lateral orbitofrontal cortex. SIGNIFICANCE STATEMENT: Learners should infer which features of environments are predictive of significant events, such as rewards. This "credit assignment" problem is particularly challenging when any of several cues might be predictive. We show that human subjects solve the credit assignment problem by implicitly "hypothesizing" which cue is relevant for predicting subsequent outcomes, and then credit is assigned according to this hypothesis. This process is associated with a distinctive pattern of activity in a part of medial frontal cortex. By contrast, when unexpected outcomes occur, hypotheses are redirected toward alternative cues, and this process is associated with activity in lateral orbitofrontal cortex. PMID- 26818501 TI - Investigating the Stability of Fine-Grain Digit Somatotopy in Individual Human Participants. AB - Studies of human primary somatosensory cortex (S1) have placed a strong emphasis on the cortical representation of the hand and the propensity for plasticity therein. Despite many reports of group differences and experience-dependent changes in cortical digit somatotopy, relatively little work has considered the variability of these maps across individuals and to what extent this detailed functional architecture is dynamic over time. With the advent of 7 T fMRI, it is increasingly feasible to map such detailed organization noninvasively in individual human participants. Here, we extend the ability of ultra-high-field imaging beyond a technological proof of principle to investigate the intersubject variability of digit somatotopy across participants and the stability of this organization across a range of intervals. Using a well validated phase-encoding paradigm and an active task, we demonstrate the presence of highly reproducible maps of individual digits in S1, sharply contrasted by a striking degree of intersubject variability in the shape, extent, and relative position of individual digit representations. Our results demonstrate the presence of very stable fine-grain somatotopy of the digits in human S1 and raise the issue of population variability in such detailed functional architecture of the human brain. These findings have implications for the study of detailed sensorimotor plasticity in the context of both learning and pathological dysfunction. The simple task and 10 min scan required to derive these maps also raises the potential for this paradigm as a tool in the clinical setting. SIGNIFICANCE STATEMENT: We applied ultra-high-resolution fMRI at 7 T to map sensory digit representations in the human primary somatosensory cortex (S1) at the level of individual participants across multiple time points. The resulting fine-grain maps of individual digits in S1 reveal the stability in this fine-grain functional organization over time, contrasted with the variability in these maps across individuals. PMID- 26818502 TI - Nucleus Accumbens Core and Shell Differentially Encode Reward-Associated Cues after Reinforcer Devaluation. AB - Nucleus accumbens (NAc) neurons encode features of stimulus learning and action selection associated with rewards. The NAc is necessary for using information about expected outcome values to guide behavior after reinforcer devaluation. Evidence suggests that core and shell subregions may play dissociable roles in guiding motivated behavior. Here, we recorded neural activity in the NAc core and shell during training and performance of a reinforcer devaluation task. Long Evans male rats were trained that presses on a lever under an illuminated cue light delivered a flavored sucrose reward. On subsequent test days, each rat was given free access to one of two distinctly flavored foods to consume to satiation and were then immediately tested on the lever pressing task under extinction conditions. Rats decreased pressing on the test day when the reinforcer earned during training was the sated flavor (devalued) compared with the test day when the reinforcer was not the sated flavor (nondevalued), demonstrating evidence of outcome-selective devaluation. Cue-selective encoding during training by NAc core (but not shell) neurons reliably predicted subsequent behavioral performance; that is, the greater the percentage of neurons that responded to the cue, the better the rats suppressed responding after devaluation. In contrast, NAc shell (but not core) neurons significantly decreased cue-selective encoding in the devalued condition compared with the nondevalued condition. These data reveal that NAc core and shell neurons encode information differentially about outcome specific cues after reinforcer devaluation that are related to behavioral performance and outcome value, respectively. SIGNIFICANCE STATEMENT: Many neuropsychiatric disorders are marked by impairments in behavioral flexibility. Although the nucleus accumbens (NAc) is required for behavioral flexibility, it is not known how NAc neurons encode this information. Here, we recorded NAc neurons during a training session in which rats learned that a cue predicted a specific reward and during a test session when that reward value was changed. Although encoding in the core during training predicted the ability of rats to change behavior after the reward value was altered, the NAc shell encoded information about the change in reward value during the test session. These findings suggest differential roles of the core and shell in behavioral flexibility. PMID- 26818503 TI - Equivalent Activities of Repulsive Axon Guidance Receptors. AB - Receptors on the growth cone at the leading edge of elongating axons play critical guidance roles by recognizing cues via their extracellular domains and transducing signals via their intracellular domains, resulting in changes in direction of growth. An important concept to have emerged in the axon guidance field is the importance of repulsion as a major guidance mechanism. Given the number and variety of different repulsive receptors, it is generally thought that there are likely to be qualitative differences in the signals they transduce. However, the nature of these possible differences is unknown. By creating chimeras using the extracellular and intracellular domains of three different Drosophila repulsive receptors, Unc5, Roundabout (Robo), and Derailed (Drl) and expressing them in defined cells within the embryonic nervous system, we examined the responses elicited by their intracellular domains systematically. Surprisingly, we found no qualitative differences in growth cone response or axon growth, suggesting that, despite their highly diverged sequences, each intracellular domain elicits repulsion via a common pathway. In terms of the signaling pathway(s) used by the repulsive receptors, mutations in the guanine nucleotide exchange factor Trio strongly enhance the repulsive activity of all three intracellular domains, suggesting that repulsion by Unc5, Robo, and Drl, and perhaps repulsion in general, involves Trio activity. SIGNIFICANCE STATEMENT: A prevailing concept that has emerged in the axon guidance field is the importance of repulsion as a guidance mechanism for steering axons to their appropriate targets. Given the number and variety of different repulsive receptors, it is generally thought that there are differences in the signals that they transduce. However, this has never been tested directly. We have used the advanced genetics of Drosophila to compare directly the outputs of different repulsive receptors. Surprisingly, we found no qualitative differences in receptor-mediated repulsion, suggesting that, despite their highly diverged domain structure, each receptor couples to a common repulsive pathway. We went on to show that this common pathway involves Trio, a guanine nucleotide exchange factor known to promote cytoskeletal remodeling. PMID- 26818504 TI - Accumulation of Laminin Monomers in Drosophila Glia Leads to Glial Endoplasmic Reticulum Stress and Disrupted Larval Locomotion. AB - The nervous system is surrounded by an extracellular matrix composed of large glycoproteins, including perlecan, collagens, and laminins. Glial cells in many organisms secrete laminin, a large heterotrimeric protein consisting of an alpha, beta, and gamma subunit. Prior studies have found that loss of laminin subunits from vertebrate Schwann cells causes loss of myelination and neuropathies, results attributed to loss of laminin-receptor signaling. We demonstrate that loss of the laminin gamma subunit (LanB2) in the peripheral glia of Drosophila melanogaster results in the disruption of glial morphology due to disruption of laminin secretion. Specifically, knockdown of LanB2 in peripheral glia results in accumulation of the beta subunit (LanB1), leading to distended endoplasmic reticulum (ER), ER stress, and glial swelling. The physiological consequences of disruption of laminin secretion in glia included decreased larval locomotion and ultimately lethality. Loss of the gamma subunit from wrapping glia resulted in a disruption in the glial ensheathment of axons but surprisingly did not affect animal locomotion. We found that Tango1, a protein thought to exclusively mediate collagen secretion, is also important for laminin secretion in glia via a collagen-independent mechanism. However loss of secretion of the laminin trimer does not disrupt animal locomotion. Rather, it is the loss of one subunit that leads to deleterious consequences through the accumulation of the remaining subunits. SIGNIFICANCE STATEMENT: This research presents a new perspective on how mutations in the extracellular matrix protein laminin cause severe consequences in glial wrapping and function. Glial-specific loss of the beta or gamma laminin subunit disrupted glia morphology and led to ER expansion and stress due to retention of other subunits. The retention of the unpaired laminin subunit was key to the glial disruption as loss of Tango1 blocked secretion of the complete laminin trimer but did not lead to glial or locomotion defects. The effects were observed in the perineurial glia that envelope the peripheral and central nervous systems, providing evidence for the importance of this class of glia in supporting nervous system function. PMID- 26818505 TI - Effects of Early and Late Bilingualism on Resting-State Functional Connectivity. AB - Of current interest is how variations in early language experience shape patterns of functional connectivity in the human brain. In the present study, we compared simultaneous (two languages from birth) and sequential (second language learned after age 5 years) bilinguals using a seed-based resting-state MRI approach. We focused on the inferior frontal gyrus (IFG) as our ROI, as recent studies have demonstrated both neurofunctional and neurostructural changes related to age of second language acquisition in bilinguals in this cortical area. Stronger functional connectivity was observed for simultaneous bilinguals between the left and right IFG, as well as between the inferior frontal gyrus and brain areas involved in language control, including the dorsolateral prefrontal cortex, inferior parietal lobule, and cerebellum. Functional connectivity between the left IFG and the right IFG and right inferior parietal lobule was also significantly correlated with age of acquisition for sequential bilinguals; the earlier the second language was acquired, the stronger was the functional connectivity. In addition, greater functional connectivity between homologous regions of the inferior frontal gyrus was associated with reduced neural activation in the left IFG during speech production. The increased connectivity at rest and reduced neural activation during task performance suggests enhanced neural efficiency in this important brain area involved in both speech production and domain-general cognitive processing. Together, our findings highlight how the brain's intrinsic functional patterns are influenced by the developmental timeline in which second language acquisition occurs. SIGNIFICANCE STATEMENT: Of current interest is how early life experience leaves its footprint on brain structure and function. In this regard, bilingualism provides an optimal way to determine the effects of the timing of language learning because a second language can be learned from birth or later in life. We used resting-state fMRI to look at simultaneous and sequential bilinguals who differed only in age of acquisition, and found stronger connectivity between language and cognitive control regions in bilinguals who learned their two languages simultaneously, a pattern that was associated with more efficient brain activation during speech. Our findings highlight how functional connections in the brain differ depending upon when learning takes place. PMID- 26818506 TI - Modulation of Orthographic Decoding by Frontal Cortex. AB - Opinions are divided on whether word reading processes occur in a hierarchical, feedforward fashion or within an interactive framework. To critically evaluate these competing theories, we recorded electrocorticographic (ECoG) data from 15 human patients with intractable epilepsy during a word completion task and evaluated brain network dynamics across individuals. We used a novel technique of analyzing multihuman ECoG recordings to identify cortical regions most relevant to processing lexical information. The mid fusiform gyrus showed the strongest, earliest response after stimulus onset, whereas activity was maximal in frontal, dorsal lateral prefrontal, and sensorimotor regions toward articulation onset. To evaluate interregional functional connectivity, ECoG data from electrodes situated over specific cortical regions of interest were fit into linear multivariate autoregressive (MVAR) models. Spectral characteristics of the MVAR models were used to precisely reveal the timing and the magnitude of information flow between localized brain regions. This is the first application of MVAR for developing a comprehensive account of interregional interactions from a word reading ECoG dataset. Our comprehensive findings revealed both top-down and bottom-up influences between higher-level language areas and the mid fusiform gyrus. Our findings thus challenge strictly hierarchical, feedforward views of word reading and suggest that orthographic processes are modulated by prefrontal and sensorimotor regions via an interactive framework. SIGNIFICANCE STATEMENT: Word reading is a critical part of everyday life. When the ability to read is disrupted, it can lead to learning disorders, as well as emotional and academic difficulties. The neural mechanisms underlying word reading are not well understood due to limitations in the spatial and temporal specificity of prior word reading studies. Our research analyzed data recorded from sensors implanted directly from surface of human brains while these individuals performed a word reading task. Our research analyzed these recordings to infer how brain regions communicate during word reading. Our original results improve upon current models of word reading and can be used to develop treatment plans for individuals with reading disabilities. PMID- 26818508 TI - Pannexin 1 Differentially Affects Neural Precursor Cell Maintenance in the Ventricular Zone and Peri-Infarct Cortex. AB - We demonstrated previously that Pannexin 1 (Panx1), an ion and metabolite channel, promotes the growth and proliferation of ventricular zone (VZ) neural precursor cells (NPCs) in vitro. To investigate its role in vivo, we used floxed Panx1 mice in combination with viruses to delete Panx1 in VZ NPCs and to track numbers of Panx1-null and Panx1-expressing VZ NPCs over time. Two days after virus injection, Panx1-null cells were less abundant than Panx1-expressing cells, suggesting that Panx1 is required for the maintenance of VZ NPCs. We also investigated the effect of Panx1 deletion in VZ NPCs after focal cortical stroke via photothrombosis. Panx1 is essential for maintaining elevated VZ NPC numbers after stroke. In contrast, Panx1-null NPCs were more abundant than Panx1 expressing NPCs in the peri-infarct cortex. Together, these findings suggest that Panx1 plays an important role in NPC maintenance in the VZ niche in the naive and stroke brain and could be a key target for improving NPC survival in the peri infarct cortex. SIGNIFICANCE STATEMENT: Here, we demonstrate that Pannexin 1 (Panx1) maintains a consistent population size of neural precursor cells in the ventricular zone, both in the healthy brain and in the context of stroke. In contrast, Panx1 appears to be detrimental to the survival of neural precursor cells that surround damaged cortical tissue in the stroke brain. This suggests that targeting Panx1 in the peri-infarct cortex, in combination with other therapies, could improve cell survival around the injury site. PMID- 26818510 TI - Neuronal Modulation in the Prefrontal Cortex in a Transitive Inference Task: Evidence of Neuronal Correlates of Mental Schema Management. AB - When informed that A > B and B > C, humans and other animals can easily conclude that A > C. This remarkable trait of advanced animals, which allows them to manipulate knowledge flexibly to infer logical relations, has only recently garnered interest in mainstream neuroscience. How the brain controls these logical processes remains an unanswered question that has been merely superficially addressed in neuroimaging and lesion studies, which are unable to identify the underlying neuronal computations. We observed that the activation pattern of neurons in the prefrontal cortex (PFC) during pair comparisons in a highly demanding transitive inference task fully supports the behavioral performance of the two monkeys that we tested. Our results indicate that the PFC contributes to the construction and use of a mental schema to represent premises. This evidence provides a novel framework for understanding the function of various areas of brain in logic processes and impairments to them in degenerative, traumatic, and psychiatric pathologies. SIGNIFICANCE STATEMENT: In cognitive neuroscience, it is unknown how information that leads to inferential deductions are encoded and manipulated at the neuronal level. We addressed this question by recording single-unit activity from the dorsolateral prefrontal cortex of monkeys that were performing a transitive inference (TI) task. The TI required one to choose the higher ranked of two items, based on previous, indirect experience. Our results demonstrated that single-neuron activity supports the construction of an abstract, mental schema of ordered items in solving the task and that this representation is independent of the reward value that is experienced for the single items. These findings identify the neural substrates of abstract mental representations that support inferential thinking. PMID- 26818507 TI - Genetic Demonstration of a Role for Stathmin in Adult Hippocampal Neurogenesis, Spinogenesis, and NMDA Receptor-Dependent Memory. AB - Neurogenesis and memory formation are essential features of the dentate gyrus (DG) area of the hippocampus, but to what extent the mechanisms responsible for both processes overlap remains poorly understood. Stathmin protein, whose tubulin binding and microtubule-destabilizing activity is negatively regulated by its phosphorylation, is prominently expressed in the DG. We show here that stathmin is involved in neurogenesis, spinogenesis, and memory formation in the DG. tTA/tetO-regulated bitransgenic mice, expressing the unphosphorylatable constitutively active Stathmin4A mutant (Stat4A), exhibit impaired adult hippocampal neurogenesis and reduced spine density in the DG granule neurons. Although Stat4A mice display deficient NMDA receptor-dependent memory in contextual discrimination learning, which is dependent on hippocampal neurogenesis, their NMDA receptor-independent memory is normal. Confirming NMDA receptor involvement in the memory deficits, Stat4A mutant mice have a decrease in the level of synaptic NMDA receptors and a reduction in learning-dependent CREB-mediated gene transcription. The deficits in neurogenesis, spinogenesis, and memory in Stat4A mice are not present in mice in which tTA/tetO-dependent transgene transcription is blocked by doxycycline through their life. The memory deficits are also rescued within 3 d by intrahippocampal infusion of doxycycline, further indicating a role for stathmin expressed in the DG in contextual memory. Our findings therefore point to stathmin and microtubules as a mechanistic link between neurogenesis, spinogenesis, and NMDA receptor-dependent memory formation in the DG. SIGNIFICANCE STATEMENT: In the present study, we aimed to clarify the role of stathmin in neuronal and behavioral functions. We characterized the neurogenic, behavioral, and molecular consequences of the gain-of-function stathmin mutation using a bitransgenic mouse expressing a constitutively active form of stathmin. We found that stathmin plays an important role in adult hippocampal neurogenesis and spinogenesis. In addition, stathmin mutation led to impaired NMDA receptor-dependent and neurogenesis-associated memory and did not affect NMDA receptor-independent memory. Moreover, biochemical analysis suggested that stathmin regulates the synaptic transport of NMDA receptors, which in turn influence CREB-mediated gene transcription machinery. Overall, these data suggest that stathmin is an important molecule for neurogenesis, spinogenesis, and NMDA receptor-dependent learning and memory. PMID- 26818511 TI - Microsaccades Are Coupled to Heartbeat. AB - During visual fixation, the eye generates microsaccades and slower components of fixational eye movements that are part of the visual processing strategy in humans. Here, we show that ongoing heartbeat is coupled to temporal rate variations in the generation of microsaccades. Using coregistration of eye recording and ECG in humans, we tested the hypothesis that microsaccade onsets are coupled to the relative phase of the R-R intervals in heartbeats. We observed significantly more microsaccades during the early phase after the R peak in the ECG. This form of coupling between heartbeat and eye movements was substantiated by the additional finding of a coupling between heart phase and motion activity in slow fixational eye movements; i.e., retinal image slip caused by physiological drift. Our findings therefore demonstrate a coupling of the oculomotor system and ongoing heartbeat, which provides further evidence for bodily influences on visuomotor functioning. SIGNIFICANCE STATEMENT: In the present study, we show that microsaccades are coupled to heartbeat. Moreover, we revealed a strong modulation of slow eye movements around the R peak in the ECG. These results suggest that heartbeat as a basic physiological signal is related to statistical modulations of fixational eye movements, in particular, the generation of microsaccades. Therefore, our findings add a new perspective on the principles underlying the generation of fixational eye movements. Importantly, our study highlights the need to record eye movements when studying the influence of heartbeat in neuroscience to avoid misinterpretation of eye-movement-related artifacts as heart-evoked modulations of neural processing. PMID- 26818509 TI - Variability in Dopamine Genes Dissociates Model-Based and Model-Free Reinforcement Learning. AB - Considerable evidence suggests that multiple learning systems can drive behavior. Choice can proceed reflexively from previous actions and their associated outcomes, as captured by "model-free" learning algorithms, or flexibly from prospective consideration of outcomes that might occur, as captured by "model based" learning algorithms. However, differential contributions of dopamine to these systems are poorly understood. Dopamine is widely thought to support model free learning by modulating plasticity in striatum. Model-based learning may also be affected by these striatal effects, or by other dopaminergic effects elsewhere, notably on prefrontal working memory function. Indeed, prominent demonstrations linking striatal dopamine to putatively model-free learning did not rule out model-based effects, whereas other studies have reported dopaminergic modulation of verifiably model-based learning, but without distinguishing a prefrontal versus striatal locus. To clarify the relationships between dopamine, neural systems, and learning strategies, we combine a genetic association approach in humans with two well-studied reinforcement learning tasks: one isolating model-based from model-free behavior and the other sensitive to key aspects of striatal plasticity. Prefrontal function was indexed by a polymorphism in the COMT gene, differences of which reflect dopamine levels in the prefrontal cortex. This polymorphism has been associated with differences in prefrontal activity and working memory. Striatal function was indexed by a gene coding for DARPP-32, which is densely expressed in the striatum where it is necessary for synaptic plasticity. We found evidence for our hypothesis that variations in prefrontal dopamine relate to model-based learning, whereas variations in striatal dopamine function relate to model-free learning. SIGNIFICANCE STATEMENT: Decisions can stem reflexively from their previously associated outcomes or flexibly from deliberative consideration of potential choice outcomes. Research implicates a dopamine-dependent striatal learning mechanism in the former type of choice. Although recent work has indicated that dopamine is also involved in flexible, goal-directed decision-making, it remains unclear whether it also contributes via striatum or via the dopamine-dependent working memory function of prefrontal cortex. We examined genetic indices of dopamine function in these regions and their relation to the two choice strategies. We found that striatal dopamine function related most clearly to the reflexive strategy, as previously shown, and that prefrontal dopamine related most clearly to the flexible strategy. These findings suggest that dissociable brain regions support dissociable choice strategies. PMID- 26818512 TI - Activation of PPARgamma Ameliorates Spatial Cognitive Deficits through Restoring Expression of AMPA Receptors in Seipin Knock-Out Mice. AB - A characteristic phenotype of congenital generalized lipodystrophy 2 (CGL2) that is caused by loss-of-function of seipin gene is mental retardation. Here, we show that seipin deficiency in hippocampal CA1 pyramidal cells caused the reduction of peroxisome proliferator-activated receptor gamma (PPARgamma). Twelve-week-old systemic seipin knock-out mice and neuronal seipin knock-out (seipin-nKO) mice, but not adipose seipin knock-out mice, exhibited spatial cognitive deficits as assessed by the Morris water maze and Y-maze, which were ameliorated by the treatment with the PPARgamma agonist rosiglitazone (rosi). In addition, seipin nKO mice showed the synaptic dysfunction and the impairment of NMDA receptor dependent LTP in hippocampal CA1 regions. The density of AMPA-induced current (IAMPA) in CA1 pyramidal cells and GluR1/GluR2 expression were significantly reduced in seipin-nKO mice, whereas the NMDA-induced current (INMDA) and NR1/NR2 expression were not altered. Rosi treatment in seipin-nKO mice could correct the decrease in expression and activity of AMPA receptor (AMPAR) and was accompanied by recovered synaptic function and LTP induction. Furthermore, hippocampal ERK2 and CREB phosphorylation in seipin-nKO mice were reduced and this could be rescued by rosi treatment. Rosi treatment in seipin-nKO mice elevated BDNF concentration. The MEK inhibitor U0126 blocked rosi-restored AMPAR expression and LTP induction in seipin-nKO mice, but the Trk family inhibitor K252a did not. These findings indicate that the neuronal seipin deficiency selectively suppresses AMPAR expression through reducing ERK-CREB activities, leading to the impairment of LTP and spatial memory, which can be rescued by PPARgamma activation. SIGNIFICANCE STATEMENT: Congenital generalized lipodystrophy 2 (CGL2), caused by loss-of-function mutation of seipin gene, is characterized by mental retardation. By the generation of systemic or neuronal seipin knock-out mice, the present study provides in vivo evidence that neuronal seipin deficiency causes deficits in spatial memory and hippocampal LTP induction. Neuronal seipin deficiency selectively suppresses AMPA receptor expression, ERK-CREB phosphorylation with the decline of PPARgamma. The PPARgamma agonist rosiglitazone can ameliorate spatial cognitive deficits and rescue the LTP induction in seipin knock-out mice by restoring AMPA receptor expression and ERK CREB activities. PMID- 26818513 TI - Female-Specific Intergenerational Transmission Patterns of the Human Corticolimbic Circuitry. AB - Parents have large genetic and environmental influences on offspring's cognition, behavior, and brain. These intergenerational effects are observed in mood disorders, with particularly robust association in depression between mothers and daughters. No studies have thus far examined the neural bases of these intergenerational effects in humans. Corticolimbic circuitry is known to be highly relevant in a wide range of processes, including mood regulation and depression. These findings suggest that corticolimbic circuitry may also show matrilineal transmission patterns. Therefore, we examined human parent-offspring association in this neurocircuitry and investigated the degree of association in gray matter volume between parent and offspring. We used voxelwise correlation analysis in a total of 35 healthy families, consisting of parents and their biological offspring. We found positive associations of regional gray matter volume in the corticolimbic circuit, including the amygdala, hippocampus, anterior cingulate cortex, and ventromedial prefrontal cortex between biological mothers and daughters. This association was significantly greater than mother son, father-daughter, and father-son associations. The current study suggests that the corticolimbic circuitry, which has been implicated in mood regulation, shows a matrilineal-specific transmission patterns. Our preliminary findings are consistent with what has been found behaviorally in depression and may have clinical implications for disorders known to have dysfunction in mood regulation such as depression. Studies such as ours will likely bridge animal work examining gene expression in the brains and clinical symptom-based observations and provide promising ways to investigate intergenerational transmission patterns in the human brain. SIGNIFICANCE STATEMENT: Parents have large genetic and environmental influences on the offspring, known as intergenerational effects. Specifically, depression has been shown to exhibit strong matrilineal transmission patterns. Although intergenerational transmission patterns in the human brain are virtually unknown, this would suggest that the corticolimbic circuitry relevant to a wide range of processes including mood regulation may also show matrilineal transmission patterns. Therefore, we examined the degree of association in corticolimbic gray matter volume (GMV) between parent and offspring in 35 healthy families. We found that positive correlations in maternal corticolimbic GMV with daughters were significantly greater than other parent-offspring dyads. Our findings provide new insight into the potential neuroanatomical basis of circuit based female-specific intergenerational transmission patterns in depression. PMID- 26818514 TI - Resolution of High-Frequency Mesoscale Intracortical Maps Using the Genetically Encoded Glutamate Sensor iGluSnFR. AB - Wide-field-of-view mesoscopic cortical imaging with genetically encoded sensors enables decoding of regional activity and connectivity in anesthetized and behaving mice; however, the kinetics of most genetically encoded sensors can be suboptimal for in vivo characterization of frequency bands higher than 1-3 Hz. Furthermore, existing sensors, in particular those that measure calcium (genetically encoded calcium indicators; GECIs), largely monitor suprathreshold activity. Using a genetically encoded sensor of extracellular glutamate and in vivo mesoscopic imaging, we demonstrate rapid kinetics of virally transduced or transgenically expressed glutamate-sensing fluorescent reporter iGluSnFR. In both awake and anesthetized mice, we imaged an 8 * 8 mm field of view through an intact transparent skull preparation. iGluSnFR revealed cortical representation of sensory stimuli with rapid kinetics that were also reflected in correlation maps of spontaneous cortical activities at frequencies up to the alpha band (8-12 Hz). iGluSnFR resolved temporal features of sensory processing such as an intracortical reverberation during the processing of visual stimuli. The kinetics of iGluSnFR for reporting regional cortical signals were more rapid than those for Emx-GCaMP3 and GCaMP6s and comparable to the temporal responses seen with RH1692 voltage sensitive dye (VSD), with similar signal amplitude. Regional cortical connectivity detected by iGluSnFR in spontaneous brain activity identified functional circuits consistent with maps generated from GCaMP3 mice, GCaMP6s mice, or VSD sensors. Viral and transgenic iGluSnFR tools have potential utility in normal physiology, as well as neurologic and psychiatric pathologies in which abnormalities in glutamatergic signaling are implicated. SIGNIFICANCE STATEMENT: We have characterized the usage of virally transduced or transgenically expressed extracellular glutamate sensor iGluSnFR to perform wide field-of-view mesoscopic imaging of cortex in both anesthetized and awake mice. Probes for neurotransmitter concentration enable monitoring of brain activity and provide a more direct measure of regional functional activity that is less dependent on nonlinearities associated with voltage-gated ion channels. We demonstrate functional maps of extracellular glutamate concentration and that this sensor has rapid kinetics that enable reporting high-frequency signaling. This imaging strategy has utility in normal physiology and pathologies in which altered glutamatergic signaling is observed. Moreover, we provide comparisons between iGluSnFR and genetically encoded calcium indicators and voltage-sensitive dyes. PMID- 26818515 TI - The Dynamic Multisensory Engram: Neural Circuitry Underlying Crossmodal Object Recognition in Rats Changes with the Nature of Object Experience. AB - Rats, humans, and monkeys demonstrate robust crossmodal object recognition (CMOR), identifying objects across sensory modalities. We have shown that rats' performance of a spontaneous tactile-to-visual CMOR task requires functional integration of perirhinal (PRh) and posterior parietal (PPC) cortices, which seemingly provide visual and tactile object feature processing, respectively. However, research with primates has suggested that PRh is sufficient for multisensory object representation. We tested this hypothesis in rats using a modification of the CMOR task in which multimodal preexposure to the to-be remembered objects significantly facilitates performance. In the original CMOR task, with no preexposure, reversible lesions of PRh or PPC produced patterns of impairment consistent with modality-specific contributions. Conversely, in the CMOR task with preexposure, PPC lesions had no effect, whereas PRh involvement was robust, proving necessary for phases of the task that did not require PRh activity when rats did not have preexposure; this pattern was supported by results from c-fos imaging. We suggest that multimodal preexposure alters the circuitry responsible for object recognition, in this case obviating the need for PPC contributions and expanding PRh involvement, consistent with the polymodal nature of PRh connections and results from primates indicating a key role for PRh in multisensory object representation. These findings have significant implications for our understanding of multisensory information processing, suggesting that the nature of an individual's past experience with an object strongly determines the brain circuitry involved in representing that object's multisensory features in memory. SIGNIFICANCE STATEMENT: The ability to integrate information from multiple sensory modalities is crucial to the survival of organisms living in complex environments. Appropriate responses to behaviorally relevant objects are informed by integration of multisensory object features. We used crossmodal object recognition tasks in rats to study the neurobiological basis of multisensory object representation. When rats had no prior exposure to the to-be-remembered objects, the spontaneous ability to recognize objects across sensory modalities relied on functional interaction between multiple cortical regions. However, prior multisensory exploration of the task-relevant objects remapped cortical contributions, negating the involvement of one region and significantly expanding the role of another. This finding emphasizes the dynamic nature of cortical representation of objects in relation to past experience. PMID- 26818516 TI - AP-1 Transcription Factors Mediate BDNF-Positive Feedback Loop in Cortical Neurons. AB - Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, regulates both survival and differentiation of several neuronal populations in the nervous system during development, as well as synaptic plasticity in the adult brain. BDNF exerts its biological functions through its receptor TrkB. Although the regulation of BDNF transcription by neuronal activity has been widely studied, little is known about TrkB signaling-dependent expression of BDNF. Using rat primary cortical neuron cultures, we show that the BDNF gene is a subject to an extensive autoregulatory loop, where TrkB signaling upregulates the expression of all major BDNF transcripts, mainly through activating MAPK pathways. Investigating the mechanisms behind this autoregulation, we found that AP-1 transcription factors, comprising Jun and Fos family members, participate in the induction of BDNF exon I, III, and VI transcripts. AP-1 transcription factors directly upregulate the expression of exon I transcripts by binding two novel AP 1 cis-elements in promoter I. Moreover, our results show that the effect of AP-1 proteins on the activity of rat BDNF promoters III and VI is indirect, because AP 1 proteins were not detected to bind the respective promoter regions by chromatin immunoprecipitation (ChIP). Collectively, we describe an extensive positive feedback system in BDNF regulation, adding a new layer to the elaborate control of BDNF gene expression. SIGNIFICANCE STATEMENT: Here, we show for the first time that in rat primary cortical neurons the expression of all major BDNF transcripts (exon I, II, III, IV, VI, and IXa transcripts) is upregulated in response to TrkB signaling, and that AP-1 transcription factors participate in the induction of exon I, III, and VI transcripts. Moreover, we have described two novel functional AP-1 cis-elements in BDNF promoter I, responsible for the activation of the promoter in response to TrkB signaling. Our results indicate the existence of a positive feedback loop for obtaining sufficient BDNF levels necessary for various TrkB signaling-dependent physiological outcomes in neurons. PMID- 26818517 TI - Neuropeptide Y Impairs Retrieval of Extinguished Fear and Modulates Excitability of Neurons in the Infralimbic Prefrontal Cortex. AB - Neuropeptide Y (NPY), a 36 aa peptide, regulates stress and emotional behaviors. Preclinical and clinical studies support an association of NPY with trauma-evoked syndromes such as posttraumatic stress disorder (PTSD), although the exact contribution of NPY is not clear. In the current study, we examined functional attributes of NPY in the infralimbic (IL) cortex, an area that regulates fear memories and is reported to be hypoactive in PTSD. Carriers of NPY gene polymorphism rs16147 have been reported to have elevated prefrontal NPY expression. Infusion of NPY into the IL cortex in rats significantly impaired fear extinction memory without affecting conditioned fear expression or acquisition of extinction. Neuroendocrine stress response, depression-like behavior, and working memory performance were not affected by NPY infusion into the IL. The NPY Y1 receptor antagonist BIBO3304 completely abolished NPY effects on fear extinction retrieval. Y1 receptor expression was localized on CaMKII positive pyramidal projection neurons and GAD67-positive interneurons in the IL. Patch-clamp recordings revealed increased inhibitory synaptic transmission onto IL projection neurons in the presence of NPY. Thus, NPY dampens excitability of IL projection neurons and impairs retrieval of extinction memory by inhibiting consolidation of extinction. Of relevance to PTSD, elevation of prefrontal NPY attributable to the genetic polymorphism rs16147 may contribute to IL hypoactivity, resulting in impaired extinction memory and susceptibility to the disorder. SIGNIFICANCE STATEMENT: Neuropeptide Y (NPY), a stress modulatory transmitter, is associated with posttraumatic stress disorder (PTSD). Contribution of NPY to PTSD symptomology is unclear. PTSD patients have reduced activity in the infralimbic (IL) subdivision of the medial prefrontal cortex (mPFC), associated with compromised extinction memory. No information exists on fear modulation by NPY in the IL cortex, although NPY and NPY receptors are abundant in these areas. This study shows that IL NPY inhibits consolidation of extinction, resulting in impaired retrieval of extinction memory and modulates excitability of IL projection neurons. In addition to providing a novel perspective on extinction memory modulation by NPY, our findings suggest that elevated mPFC NPY in gene polymorphism rs16147 carriers or after chronic stress could increase susceptibility to PTSD. PMID- 26818518 TI - Rho Kinase Inhibition as a Therapeutic for Progressive Supranuclear Palsy and Corticobasal Degeneration. AB - Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative four-repeat tauopathies with no cure. Mitigating pathogenic tau levels is a rational strategy for tauopathy treatment, but therapeutic targets with clinically available drugs are lacking. Here, we report that protein levels of the Rho-associated protein kinases (ROCK1 and ROCK2), p70 S6 kinase (S6K), and mammalian target of rapamycin (mTOR) were increased in PSP and CBD brains. RNAi depletion of ROCK1 or ROCK2 reduced tau mRNA and protein level in human neuroblastoma cells. However, additional phenotypes were observed under ROCK2 knockdown, including decreased S6K and phosphorylated mTOR levels. Pharmacologic inhibition of Rho kinases in neurons diminished detergent-soluble and -insoluble tau through a combination of autophagy enhancement and tau mRNA reduction. Fasudil, a clinically approved ROCK inhibitor, suppressed rough eye phenotype and mitigated pathogenic tau levels by inducing autophagic pathways in a Drosophila model of tauopathy. Collectively, these findings highlight the Rho kinases as rational therapeutic targets to combat tau accumulation in PSP and CBD. SIGNIFICANCE STATEMENT: Studies of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) suggest that mitigating pathogenic tau levels is a rational strategy for tauopathy treatment. In this report, the Rho-associated protein kinases (ROCK1 and ROCK2) are identified as novel drug targets for PSP and CBD. We show that elevated insoluble tau levels are associated with increased ROCK1 and ROCK2 in PSP and CBD brains, whereas experiments in cellular and animal models identify pharmacologic inhibition of ROCKs as a mechanism-based approach to reduce tau levels. Our study correlates bona fide changes in PSP and CBD brains with cellular models, identifies drug targets, and tests the therapeutic in vivo. PMID- 26818520 TI - Platelet-Activating Factor Receptors Mediate Excitatory Postsynaptic Hippocampal Injury in Experimental Autoimmune Encephalomyelitis. AB - Gray matter degeneration contributes to progressive disability in multiple sclerosis (MS) and can occur out of proportion to measures of white matter disease. Although white matter pathology, including demyelination and axon injury, can lead to secondary gray matter changes, we hypothesized that neurons can undergo direct excitatory injury within the gray matter independent of these. We tested this using a model of experimental autoimmune encephalomyelitis (EAE) with hippocampal degeneration in C57BL/6 mice, in which immunofluorescent staining showed a 28% loss of PSD95-positive excitatory postsynaptic puncta in hippocampal area CA1 compared with sham-immunized controls, despite preservation of myelin and VGLUT1-positive excitatory axon terminals. Loss of postsynaptic structures was accompanied by appearance of PSD95-positive debris that colocalized with the processes of activated microglia at 25 d after immunization, and clearance of debris was followed by persistently reduced synaptic density at 55 d. In vitro, addition of activated BV2 microglial cells to hippocampal cultures increased neuronal vulnerability to excitotoxic dendritic damage following a burst of synaptic activity in a manner dependent on platelet activating factor receptor (PAFR) signaling. In vivo treatment with PAFR antagonist BN52021 prevented PSD95-positive synapse loss in hippocampi of mice with EAE but did not affect development of EAE or local microglial activation. These results demonstrate that postsynaptic structures can be a primary target of injury within the gray matter in autoimmune neuroinflammatory disease, and suggest that this may occur via PAFR-mediated modulation of activity-dependent synaptic physiology downstream of microglial activation. SIGNIFICANCE STATEMENT: Unraveling gray matter degeneration is critical for developing treatments for progressive disability and cognitive impairment in multiple sclerosis (MS). In a mouse model of MS, we show that neurons can undergo injury at their synaptic connections within the gray matter, independent of the white matter pathology, demyelination, and axon injury that have been the focus of most current and emerging treatments. Damage to excitatory synapses in the hippocampus occurs in association with activated microglia, which can promote excitotoxic injury via activation of receptors for platelet-activating factor, a proinflammatory signaling molecule elevated in the brain in MS. Platelet-activating factor receptor blockade protected synapses in the mouse model, identifying a potential target for neuroprotective treatments in MS. PMID- 26818522 TI - Conformational Changes in Transmembrane Domain 4 of Presenilin 1 Are Associated with Altered Amyloid-beta 42 Production. AB - gamma-Secretase is an intramembrane-cleaving protease that produces amyloid-beta peptide 42 (Abeta42), which is the toxic and aggregation-prone species of Abeta that causes Alzheimer's disease. Here, we used the substituted cysteine accessibility method to analyze the structure of transmembrane domains (TMDs) 4 and 5 of human presenilin 1 (PS1), a catalytic subunit of gamma-secretase. We revealed that TMD4 and TMD5 face the intramembranous hydrophilic milieu together with TMD1, TMD6, TMD7, and TMD9 of PS1 to form the catalytic pore structure. Notably, we found a correlation in the distance between the cytosolic sides of TMD4/TMD7 and Abeta42 production levels, suggesting that allosteric conformational changes of the cytosolic side of TMD4 affect Abeta42-generating gamma-secretase activity. Our results provide new insights into the relationship between the structure and activity of human PS1. SIGNIFICANCE STATEMENT: Modulation of gamma-secretase activity to reduce toxic amyloid-beta peptide species is one plausible therapeutic approaches for Alzheimer's disease. However, precise mechanistic information of gamma-secretase still remains unclear. Here we identified the conformational changes in transmembrane domains of presenilin 1 that affect the proteolytic activity of the gamma-secretase. Our results highlight the importance of understanding the structural dynamics of presenilin 1 in drug development against Alzheimer's disease. PMID- 26818519 TI - Obesity Weighs down Memory through a Mechanism Involving the Neuroepigenetic Dysregulation of Sirt1. AB - Aberrant gene expression within the hippocampus has recently been implicated in the pathogenesis of obesity-induced memory impairment. Whether a dysregulation of epigenetic modifications mediates this disruption in gene transcription has yet to be established. Here we report evidence of obesity-induced alterations in DNA methylation of memory-associated genes, including Sirtuin 1 (Sirt1), within the hippocampus, and thus offer a novel mechanism by which SIRT1 expression within the hippocampus is suppressed during obesity. Forebrain neuron-specific Sirt1 knock-out closely recapitulated the memory deficits exhibited by obese mice, consistent with the hypothesis that the high-fat diet-mediated reduction of hippocampal SIRT1 could be responsible for obesity-linked memory impairment. Obese mice fed a diet supplemented with the SIRT1-activating molecule resveratrol exhibited increased hippocampal SIRT1 activity and preserved hippocampus dependent memory, further strengthening this conclusion. Thus, our findings suggest that the memory-impairing effects of diet-induced obesity may potentially be mediated by neuroepigenetic dysregulation of SIRT1 within the hippocampus. SIGNIFICANCE STATEMENT: Previous studies have implicated transcriptional dysregulation within the hippocampus as being a relevant pathological concomitant of obesity-induced memory impairment, yet a deeper understanding of the basis for, and etiological significance of, transcriptional dysregulation in this context is lacking. Here we present the first evidence of epigenetic dysregulation (i.e., altered DNA methylation and hydroxymethylation) of memory related genes, including Sirt1, within the hippocampus of obese mice. Furthermore, experiments using transgenic and pharmacological approaches strongly implicate reduced hippocampal SIRT1 as being a principal pathogenic mediator of obesity-induced memory impairment. This paper offers a novel working model that may serve as a conceptual basis for the development of therapeutic interventions for obesity-induced memory impairment. PMID- 26818521 TI - MEKK4 Signaling Regulates Sensory Cell Development and Function in the Mouse Inner Ear. AB - Mechanosensory hair cells (HCs) residing in the inner ear are critical for hearing and balance. Precise coordination of proliferation, sensory specification, and differentiation during development is essential to ensure the correct patterning of HCs in the cochlear and vestibular epithelium. Recent studies have revealed that FGF20 signaling is vital for proper HC differentiation. However, the mechanisms by which FGF20 signaling promotes HC differentiation remain unknown. Here, we show that mitogen-activated protein 3 kinase 4 (MEKK4) expression is highly regulated during inner ear development and is critical to normal cytoarchitecture and function. Mice homozygous for a kinase inactive MEKK4 mutation exhibit significant hearing loss. Lack of MEKK4 activity in vivo also leads to a significant reduction in the number of cochlear and vestibular HCs, suggesting that MEKK4 activity is essential for overall development of HCs within the inner ear. Furthermore, we show that loss of FGF20 signaling in vivo inhibits MEKK4 activity, whereas gain of Fgf20 function stimulates MEKK4 expression, suggesting that Fgf20 modulates MEKK4 activity to regulate cellular differentiation. Finally, we demonstrate, for the first time, that MEKK4 acts as a critical node to integrate FGF20-FGFR1 signaling responses to specifically influence HC development and that FGFR1 signaling through activation of MEKK4 is necessary for outer hair cell differentiation. Collectively, this study provides compelling evidence of an essential role for MEKK4 in inner ear morphogenesis and identifies the requirement of MEKK4 expression in regulating the specific response of FGFR1 during HC development and FGF20/FGFR1 signaling activated MEKK4 for normal sensory cell differentiation. SIGNIFICANCE STATEMENT: Sensory hair cells (HCs) are the mechanoreceptors within the inner ear responsible for our sense of hearing. HCs are formed before birth, and mammals lack the ability to restore the sensory deficits associated with their loss. In this study, we show, for the first time, that MEKK4 signaling is essential for the development of normal cytoarchitecture and hearing function as MEKK4 signaling-deficient mice exhibit a significant reduction of HCs and a hearing loss. We also identify MEKK4 as a critical hub kinase for FGF20-FGFR1 signaling to induce HC differentiation in the mammalian cochlea. These results reveal a new paradigm in the regulation of HC differentiation and provide significant new insights into the mechanism of Fgf signaling governing HC formation. PMID- 26818523 TI - Age-Related Phasic Patterns of Mitochondrial Maintenance in Adult Caenorhabditis elegans Neurons. AB - Aging is associated with cognitive decline and increasing risk of neurodegeneration. Perturbation of mitochondrial function, dynamics, and trafficking are implicated in the pathogenesis of several age-associated neurodegenerative diseases. Despite this fundamental importance, the critical understanding of how organismal aging affects lifetime neuronal mitochondrial maintenance remains unknown, particularly in a physiologically relevant context. To address this issue, we performed a comprehensive in vivo analysis of age associated changes in mitochondrial morphology, density, trafficking, and stress resistance in individual Caenorhabditis elegans neurons throughout adult life. Adult neurons display three distinct stages of increase, maintenance, and decrease in mitochondrial size and density during adulthood. Mitochondrial trafficking in the distal neuronal processes declines progressively with age starting from early adulthood. In contrast, long-lived daf-2 mutants exhibit delayed age-associated changes in mitochondrial morphology, constant mitochondrial density, and maintained trafficking rates during adulthood. Reduced mitochondrial load at late adulthood correlates with decreased mitochondrial resistance to oxidative stress. Revealing aging-associated changes in neuronal mitochondria in vivo is an essential precedent that will allow future elucidation of the mechanistic causes of mitochondrial aging. Thus, our study establishes the critical foundation for the future analysis of cellular pathways and genetic and pharmacological factors regulating mitochondrial maintenance in aging- and disease-relevant conditions. SIGNIFICANCE STATEMENT: Using Caenorhabditis elegans as a model, we address long-standing questions: How does aging affect neuronal mitochondrial morphology, density, trafficking, and oxidative stress resistance? Are these age-related changes amenable to genetic manipulations that slow down the aging process? Our study illustrates that mitochondrial trafficking declines progressively from the first day of adulthood, whereas mitochondrial size, density, and resistance to oxidative stress undergo three distinct stages: increase in early adulthood, maintenance at high levels during mid-adulthood, and decline during late adulthood. Thus, our study characterizes mitochondrial aging profile at the level of a single neuron in its native environment and establishes the critical foundation for the future genetic and pharmacological dissection of factors that influence long-term mitochondrial maintenance in neurons. PMID- 26818525 TI - Phase of Spontaneous Slow Oscillations during Sleep Influences Memory-Related Processing of Auditory Cues. AB - Slow oscillations during slow-wave sleep (SWS) may facilitate memory consolidation by regulating interactions between hippocampal and cortical networks. Slow oscillations appear as high-amplitude, synchronized EEG activity, corresponding to upstates of neuronal depolarization and downstates of hyperpolarization. Memory reactivations occur spontaneously during SWS, and can also be induced by presenting learning-related cues associated with a prior learning episode during sleep. This technique, targeted memory reactivation (TMR), selectively enhances memory consolidation. Given that memory reactivation is thought to occur preferentially during the slow-oscillation upstate, we hypothesized that TMR stimulation effects would depend on the phase of the slow oscillation. Participants learned arbitrary spatial locations for objects that were each paired with a characteristic sound (eg, cat-meow). Then, during SWS periods of an afternoon nap, one-half of the sounds were presented at low intensity. When object location memory was subsequently tested, recall accuracy was significantly better for those objects cued during sleep. We report here for the first time that this memory benefit was predicted by slow-wave phase at the time of stimulation. For cued objects, location memories were categorized according to amount of forgetting from pre- to post-nap. Conditions of high versus low forgetting corresponded to stimulation timing at different slow oscillation phases, suggesting that learning-related stimuli were more likely to be processed and trigger memory reactivation when they occurred at the optimal phase of a slow oscillation. These findings provide insight into mechanisms of memory reactivation during sleep, supporting the idea that reactivation is most likely during cortical upstates. SIGNIFICANCE STATEMENT: Slow-wave sleep (SWS) is characterized by synchronized neural activity alternating between active upstates and quiet downstates. The slow-oscillation upstates are thought to provide a window of opportunity for memory consolidation, particularly conducive to cortical plasticity. Recent evidence shows that sensory cues associated with previous learning can be delivered subtly during SWS to selectively enhance memory consolidation. Our results demonstrate that this behavioral benefit is predicted by slow-oscillation phase at stimulus presentation time. Cues associated with high versus low forgetting based on analysis of subsequent recall performance were delivered at opposite slow-oscillation phases. These results provide evidence of an optimal slow-oscillation phase for memory consolidation during sleep, supporting the idea that memory processing occurs preferentially during cortical upstates. PMID- 26818524 TI - Dynamics of Phosphoinositide-Dependent Signaling in Sympathetic Neurons. AB - In neurons, loss of plasma membrane phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] leads to a decrease in exocytosis and changes in electrical excitability. Restoration of PI(4,5)P2 levels after phospholipase C activation is therefore essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We measured dynamic changes of PI(4,5)P2, phosphatidylinositol 4-phosphate, diacylglycerol, inositol 1,4,5-trisphosphate, and Ca(2+) upon muscarinic stimulation in sympathetic neurons from adult male Sprague-Dawley rats with electrophysiological and optical approaches. We used this kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show and explain faster synthesis of PI(4,5)P2 in sympathetic neurons than in electrically nonexcitable tsA201 cells. They can be used to understand dynamic effects of receptor-mediated phospholipase C activation on excitability and other PI(4,5)P2-dependent processes in neurons. SIGNIFICANCE STATEMENT: Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a minor phospholipid in the cytoplasmic leaflet of the plasma membrane. Depletion of PI(4,5)P2 via phospholipase C-mediated hydrolysis leads to a decrease in exocytosis and alters electrical excitability in neurons. Restoration of PI(4,5)P2 is essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We studied the dynamics of phosphoinositide metabolism in sympathetic neurons upon muscarinic stimulation and used the kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show a several-fold faster synthesis of PI(4,5)P2 in sympathetic neurons than in an electrically nonexcitable cell line, and provide a framework for future studies of PI(4,5)P2-dependent processes in neurons. PMID- 26818526 TI - Neurodegeneration Triggers Peripheral Immune Cell Recruitment into the Forebrain. AB - Brain-intrinsic degenerative cascades have been proposed to be an initial factor driving lesion formation in multiple sclerosis (MS). Here, we identify neurodegeneration as a potent trigger for peripheral immune cell recruitment into the mouse forebrain. Female C57BL/6 mice were fed cuprizone for 3 weeks, followed by a period of 2 weeks on normal chow to induce the formation of lesion foci in the forebrain. Subsequent immunization with myelin oligodendrocyte glycoprotein 35-55 peptide, which induces myelin autoreactive T cells in the periphery, resulted in massive immune cell recruitment into the affected forebrain. Additional adoptive transfer experiments together with flow cytometry analysis underline the importance of brain-derived signals for immune cell recruitment. This study clearly illustrates the significance of brain-intrinsic degenerative cascades for immune cell recruitment and MS lesion formation. Additional studies have to address the signaling cascades and mechanistic processes that form the top-down communication between the affected brain area, neurovascular unit, and peripheral immune cells. SIGNIFICANCE STATEMENT: We identify neurodegeneration as a potent trigger for peripheral immune cell recruitment into the forebrain. Thus, immune cell recruitment might be a second step during the formation of new inflammatory lesions in multiple sclerosis. A better understanding of factors regulating neurodegeneration-induced immune cell recruitment will pave the way for the development of novel therapeutic treatment strategies. PMID- 26818528 TI - Transcranial Stimulation of the Dorsolateral Prefrontal Cortex Prevents Stress Induced Working Memory Deficits. AB - Stress is known to impair working memory performance. This disruptive effect of stress on working memory has been linked to a decrease in the activity of the dorsolateral prefrontal cortex (dlPFC). In the present experiment, we tested whether transcranial direct current stimulation (tDCS) of the dlPFC can prevent stress-induced working memory impairments. We tested 120 healthy participants in a 2 d, sham-controlled, double-blind between-subjects design. Participants completed a test of their individual baseline working memory capacity on day 1. On day 2, participants were exposed to either a stressor or a control manipulation before they performed a visuospatial and a verbal working memory task. While participants completed the tasks, anodal, cathodal, or sham tDCS was applied over the right dlPFC. Stress impaired working memory performance in both tasks, albeit to a lesser extent in the verbal compared with the visuospatial working memory task. This stress-induced working memory impairment was prevented by anodal, but not sham or cathodal, stimulation of the dlPFC. Compared with sham or cathodal stimulation, anodal tDCS led to significantly better working memory performance in both tasks after stress. Our findings indicate a causal role of the dlPFC in working memory impairments after acute stress and point to anodal tDCS as a promising tool to reduce cognitive deficits related to working memory in stress-related mental disorders, such as depression, schizophrenia, or post traumatic stress disorder. SIGNIFICANCE STATEMENT: Working memory deficits are prominent in stress-related mental disorders, such as depression, schizophrenia, or post-traumatic stress disorder. Similar working memory impairments have been observed in healthy individuals exposed to acute stress. So far, attempts to prevent such stress-induced working memory deficits focused mainly on pharmacological interventions. Here, we tested the idea that transcranial direct current stimulation of the dorsolateral prefrontal cortex (dlPFC), a critical neural substrate of working memory, may prevent working memory impairments after stress. Our results indicate that anodal stimulation of the dlPFC may indeed preserve working memory performance under stress, suggesting that the dlPFC plays a causal role in stress-induced working memory deficits and pointing to a potential new avenue to prevent stress-induced cognitive impairments. PMID- 26818527 TI - Functional Topography of Human Auditory Cortex. AB - Functional and anatomical studies have clearly demonstrated that auditory cortex is populated by multiple subfields. However, functional characterization of those fields has been largely the domain of animal electrophysiology, limiting the extent to which human and animal research can inform each other. In this study, we used high-resolution functional magnetic resonance imaging to characterize human auditory cortical subfields using a variety of low-level acoustic features in the spectral and temporal domains. Specifically, we show that topographic gradients of frequency preference, or tonotopy, extend along two axes in human auditory cortex, thus reconciling historical accounts of a tonotopic axis oriented medial to lateral along Heschl's gyrus and more recent findings emphasizing tonotopic organization along the anterior-posterior axis. Contradictory findings regarding topographic organization according to temporal modulation rate in acoustic stimuli, or "periodotopy," are also addressed. Although isolated subregions show a preference for high rates of amplitude modulated white noise (AMWN) in our data, large-scale "periodotopic" organization was not found. Organization by AM rate was correlated with dominant pitch percepts in AMWN in many regions. In short, our data expose early auditory cortex chiefly as a frequency analyzer, and spectral frequency, as imposed by the sensory receptor surface in the cochlea, seems to be the dominant feature governing large-scale topographic organization across human auditory cortex. SIGNIFICANCE STATEMENT: In this study, we examine the nature of topographic organization in human auditory cortex with fMRI. Topographic organization by spectral frequency (tonotopy) extended in two directions: medial to lateral, consistent with early neuroimaging studies, and anterior to posterior, consistent with more recent reports. Large-scale organization by rates of temporal modulation (periodotopy) was correlated with confounding spectral content of amplitude-modulated white-noise stimuli. Together, our results suggest that the organization of human auditory cortex is driven primarily by its response to spectral acoustic features, and large-scale periodotopy spanning across multiple regions is not supported. This fundamental information regarding the functional organization of early auditory cortex will inform our growing understanding of speech perception and the processing of other complex sounds. PMID- 26818529 TI - Human Imaging With Photon Counting-Based Computed Tomography at Clinical Dose Levels: Contrast-to-Noise Ratio and Cadaver Studies. AB - OBJECTIVES: The purpose of this work was to measure and compare the iodine contrast-to-noise ratio (CNR) between a commercial energy-integrating detector (EID) computed tomography (CT) system and a photon-counting detector (PCD) CT scanner capable of human imaging at clinical dose rates, as well as to determine clinical feasibility using human cadavers. MATERIALS AND METHODS: A research dual source PCD-CT scanner was used, where the "A" tube/detector subsystem used an EID and the "B" tube/detector subsystem used a PCD. Iodine CNR was measured in 4 anthropomorphic phantoms, simulating 4 patient sizes, at 4 tube potential settings. After biospecimen committee approval, PCD scans were performed on a fresh-frozen human head and a whole-body cadaver using clinical dose rates. Scans were repeated using the EID and identical parameters, and qualitative side-by side comparisons were performed. RESULTS: For the same photon fluence, phantom measurements demonstrated a mean increase in CNR of 11%, 23%, 31%, 38% for the PCD system, relative to the EID system, at 80, 100, 120, and 140 kV, respectively. Photon-counting detector CT additionally provided energy-selective imaging, where low- and high-energy images reflected the energy dependence of the iodine signal. Photon-counting detector images of cadaveric anatomy demonstrated decreased beam hardening and calcium blooming in the high-energy bin images and increased contrast in the low-energy bins images relative to the EID images. Threshold-based PCD images were qualitatively deemed equivalent in other aspects. CONCLUSIONS: The evaluated research PCD-CT system was capable of clinical levels of image quality at clinical dose rates. It further provided improved CNR relative to state-of-the-art EID-CT. The energy-selective bin images provide further opportunity for dual-energy and multienergy analyses. PMID- 26818530 TI - Association between leukocyte telomere length and serum carotenoid in US adults. AB - PURPOSE: Telomere length is a biomarker for aging. It is known that oxidative stress can accelerate telomere shortening, whereas antioxidants can delay their shortening. Carotenoids as antioxidants are favorably associated with health- and aging-related diseases caused by oxidative stress, but their association with telomere length is less certain. We investigated the association between blood carotenoid levels and leukocyte telomere length in a representative sample of US adults. METHODS: We analyzed 3660 participants aged 20 years and older in the 1999-2002 National Health and Nutrition Examination Survey. The levels of carotenoids-alpha-carotene, beta-carotene (trans + cis), beta-cryptoxanthin, combined lutein/zeaxanthin, and trans-lycopene-were measured using high performance liquid chromatography. The leukocyte telomere length (T/S ratio) was assayed using the quantitative polymerase chain reaction method. RESULTS: A doubling of blood alpha-carotene, beta-carotene (trans + cis), and beta cryptoxanthin was associated with approximately 2 % longer telomeres. Compared with the lowest carotenoid quartile of alpha-carotene, beta-carotene (trans + cis), and beta-cryptoxanthin, telomere length for adults with the highest quartiles was significantly increased by 5-8 %. CONCLUSION: We found that increasing levels of blood carotenoid were significantly associated with longer leukocyte telomeres in US adults. High intake of carotenoid-rich food may play a role in protecting telomeres and regulating telomere length. PMID- 26818532 TI - Flexible all solid state supercapacitor with high energy density employing black titania nanoparticles as a conductive agent. AB - Increasing the electrical conductivity of pseudocapacitive materials without changing their morphology is an ideal structural solution to realize both high electrochemical performance and superior flexibility for an all solid state supercapacitor (ASSSC). Herein, we fabricate a flexible ASSSC device employing black titania (TiO2-x:N) decorated two-dimensional (2D) NiO nanosheets as the positive electrode and mesoporous graphene as the negative electrode. In this unique design, NiO nanosheets are used as pseudocapacitive materials and TiO2-x:N nanoparticles serve as the conductive agent. Owing to the excellent electrical conductivity of TiO2-x:N and well defined "particle on sheet" planar structure of NiO/TiO2-x:N composites, the 2D morphology of the decorated NiO nanosheets is completely retained, which efficiently reinforces the pseudocapacitive activity and flexibility of the whole all solid state device. The maximum specific capacitance of fabricated the NiO/TiO2-x:N//mesoporous graphene supercapacitor can reach 133 F g(-1), which is 2 and 4 times larger than the values of the NiO based ASSSC employing graphene and carbon black as the conductive agent, respectively. In addition, the optimized ASSSC displays intriguing performances with an energy density of 47 W h kg(-1) in a voltage region of 0-1.6 V, which is, to the best of our knowledge, the highest value for flexible ASSSC devices. The impressive results presented here may pave the way for promising applications of black titania in high energy density flexible storage systems. PMID- 26818531 TI - Sorting Nexin 11 Regulates Lysosomal Degradation of Plasma Membrane TRPV3. AB - The trafficking of ion channels to/from the plasma membrane is considered an important mechanism for cellular activity and an interesting approach for disease therapies. The transient receptor potential vanilloid 3 (TRPV3) ion channel is widely expressed in skin keratinocytes, and its trafficking mechanism to/from the plasma membrane is unknown. Here, we report that the vesicular trafficking protein sorting nexin 11 (SNX11) downregulates the level of the TRPV3 plasma membrane protein. Overexpression of SNX11 causes a decrease in the level of TRPV3 current and TRPV3 plasma membrane protein in TRPV3-transfected HEK293T cells. Subcellular localizations and western blots indicate that SNX11 interacts with TRPV3 and targets it to lysosomes for degradation, which is blocked by the lysosomal inhibitors chloroquine and leupeptin. Both TRPV3 and SNX11 are highly expressed in HaCaT cells. We show that TRPV3 agonists-activated Ca(2+) influxes and the level of native TRPV3 total protein in HaCaT cells are decreased by overexpression of SNX11 and increased by knockdown of SNX11. Our findings reveal that SNX11 promotes the trafficking of TRPV3 from the plasma membrane to lysosomes for degradation via protein-protein interactions, which demonstrates a previously unknown function of SNX11 as a regulator of TRPV3 trafficking from the plasma membrane to lysosomes. PMID- 26818533 TI - Fostering Self-Compassion and Loving-Kindness in Patients With Borderline Personality Disorder: A Randomized Pilot Study. AB - : The aim of this randomized pilot study is to investigate the effects of a short training programme in loving-kindness and compassion meditation (LKM/CM) in patients with borderline personality disorder. Patients were allocated to LKM/CM or mindfulness continuation training (control group). Patients in the LKM/CM group showed greater changes in Acceptance compared with the control group. Remarkable changes in borderline symptomatology, self-criticism and self-kindness were also observed in the LKM/CM group. Mechanistic explanations and therapeutic implications of the findings are discussed. HIGHLIGHTS: Three weeks of loving kindness and compassion meditations increased acceptance of the present-moment experience in patients with borderline personality disorder. Significant improvements in the severity of borderline symptoms, self-criticism, mindfulness, acceptance and self-kindness were observed after the LKM/CM intervention. LKM/CM is a promising complementary strategy for inclusion in mindfulness-based interventions and Dialectical Behavioural Therapy for treating core symptoms in borderline personality disorder. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26818534 TI - CRISPRi-Manipulation of Genetic Code Expansion via RF1 for Reassignment of Amber Codon in Bacteria. AB - The precise engineering of proteins in bacteria via the amber codon has been hampered by the poor incorporation of unnatural amino acid (UAA). Here we explored the amber assignment as a sense codon for UAA by CRISPRi targeting release factor 1 (RF1). Scanning of RF1 gene with sgRNAs identified target loci that differentiate RF1 repressions. Quantitation of RF1 repressions versus UAA incorporation indicated an increasing interrelation with the amber reassignment maximized upon RF1 knockdown to ~30%, disclosing the beneficial role of RF1 in amber assignment. However, further RF1 repression reversed this trend resulting from the detrimental effects on host cell growth, disclosing the harmful aspect of RF1 in reassignment of the amber codon. Our data indicate RF1 as a switch manipulating genetic code expansion and pave a direction via CRISPRi for precise engineering and efficient production of proteins in bacteria. PMID- 26818535 TI - Antipsychotic Use and Metabolic Monitoring in Individuals with Developmental Disabilities Served in a Medicaid Medical Home. AB - This study describes antipsychotic use and metabolic monitoring rates among individuals with developmental disabilities enrolled in a subspecialty medical home (N = 826). Four hundred ninety-nine participants (60.4 %) were taking antipsychotics, which was associated with male gender (p = 0.01), intellectual disability with and without autism spectrum disorder (p = 0.001 and p = 0.04, respectively), and inversely associated with the youngest and oldest age categories (p = 0.001 and p = 0.04, respectively). Among those taking antipsychotics, annual metabolic monitoring rates ranged from 89 % (lipids) to 99 % (weight). Age was positively associated with glucose (p < 0.001) and lipid monitoring (p < 0.001). Adult participants with dyslipidemia (p < 0.01), prediabetes/diabetes (p = 0.04), and hypertension (p = 0.02) were significantly more likely to obtain lipid monitoring. These values exceeded previously reported rates suggesting the importance of an integrated care model. PMID- 26818537 TI - The journal in its fourth five-year publication. PMID- 26818536 TI - Role of long non-coding RNA MIAT in proliferation, apoptosis and migration of lens epithelial cells: a clinical and in vitro study. AB - Age-related cataract is among the most common chronic disorders of ageing and is the world's leading blinding disorder. Long non-coding RNAs play important roles in several biological processes and complicated diseases. However, the role of lncRNAs in the setting of cataract is still unknown. Here, we extracted total RNAs from the transparent and age-matched cataractous human lenses, and determined lncRNA expression profiles using microarray analysis. We found that 38 lncRNAs were differentially expressed between transparent and cataractous lenses. 17 of 20 differentially expressed lncRNAs were further verified by quantitative RT-PCRs. One top abundant lncRNA, MIAT, was specifically up-regulated both in the plasma fraction of whole blood and aqueous humor of cataract patients. MIAT knockdown could affect the proliferation, apoptosis and migration of Human lens epithelial cells (HLECs) upon oxidative stress. Posterior capsule opacification (PCO) is a common complication of cataract surgery, which is associated with abnormal production of inflammatory factors. MIAT knockdown could repress tumour necrosis factor-alpha-induced abnormal proliferation and migration of HLECs, suggesting a potential role of MIAT in PCO-related pathological process. Moreover, we found that MIAT acted as a ceRNA, and formed a feedback loop with Akt and miR-150-5p to regulate HLEC function. Collectively, this study provides a novel insight into the pathogenesis of age-related cataract. PMID- 26818538 TI - Risk factors for bile leakage after hepatectomy. PMID- 26818539 TI - Postoperative outcomes after open splenectomy versus laparoscopic splenectomy in cirrhotic patients: a meta-analysis. AB - BACKGROUND: Laparoscopic splenectomy is considered the gold standard for resecting normal-to-moderately bigger spleens in benign conditions, and in addition could be tried for patients with malignant splenic disorders. However, the safety of laparoscopic splenectomy in patients with hypersplenism is not well known. This study aimed to investigate the efficacy and safety of laparoscopic splenectomy for patients with hypersplenism secondary to liver cirrhosis by comparing with the open splenectomy. DATA SOURCES: Several databases were searched to identify comparative studies fulfilling the predefined selection criteria from January 2000 to June 2015. The subsequent key words were utilized for browsing "laparoscopy" or "laparoscopic", "open", "splenectomy", and "liver cirrhosis". Studies evaluating laparoscopic and open splenectomy for patients with liver cirrhosis were incorporated. Two evaluators personally strained the title and abstract of each publication. Citations with contemplated compliance within our eligibility criteria underwent compressed review. Meta-analysis was carried out according to the recommendations of the Cochrane Collaboration software (review manager 5.1). RESULTS: Seven studies containing 509 patients were included. Compared with the open splenectomy group, patients in the laparoscopic splenectomy group had significantly less intraoperative blood loss (MD=210.30; 95% CI: 11.28-409.32; P=0.04), longer operative time (MD=-31.58; 95% CI: -53.34--9.82; P=0.004), shorter duration of postoperative hospital stay (MD=3.41; 95% CI: 2.39-4.43; P<0.01), lower incidence of postoperative complications (RR=1.34; 95% CI: 0.88-2.01; P=0.17), and decreased liver damage [ALT (MD=8.52; 95% CI: 0.19-16.85; P=0.05) and total bilirubin (MD=5.12; 95% CI: 0.37-9.87; P=0.03)]. CONCLUSION: Hypersplenism secondary to cirrhosis and portal hypertension should not be a contraindication for laparoscopic splenectomy. PMID- 26818540 TI - Giant cavernous liver hemangiomas: is it the time to change the size categories? AB - BACKGROUND: Four different sizes (4, 5, 8 and 10 cm in diameter) can be found in the literature to categorize a liver hemangioma as giant. The present review aims to clarify the appropriateness of the size category "giant" for liver hemangioma. DATA SOURCES: We reviewed the reports on the categorization of hemangioma published between 1970 and 2014. The number of hemangiomas, size criteria, mean and range of hemangioma sizes, and number of asymptomatic and symptomatic patients were investigated in patients aged over 18 years. Liver hemangiomas were divided into four groups: <5.0 cm, 5.0-9.9 cm, 10.0-14.9 cm and >=15.0 cm in diameter. Inclusion criteria were noted in 34 articles involving 1972 (43.0%) hemangiomas (>4.0 cm). RESULTS: The patients were divided into the following groups: 154 patients (30.0%) with hemangiomas less than 5.0 cm in diameter (small), 182 (35.5%) between 5.0 cm and 9.9 cm (large), 75 (14.6%) between 10.0 and 14.9 cm (giant), and 102 (19.9%) more than 15.0 cm (enormous). There were 786 (39.9%) asymptomatic patients and 791 (40.1%) symptomatic patients. Indications for surgery related to symptoms were reported in only 75 (3.8%) patients. Operations including 137 non-anatomical resection (12.9%) and 469 enucleation (44.1%) were unclearly related to size and symptoms. CONCLUSIONS: The term "giant" seems to be justified for liver hemangiomas with a diameter of 10 cm. Hemangiomas categorized as "giant" are not indicated for surgery. Surgery should be performed only when other symptoms are apparent. PMID- 26818541 TI - Pancreatic metastasis of renal cell carcinoma. AB - BACKGROUND: Renal cell carcinoma (RCC) is a common cancer, but pancreatic metastasis of RCC is unusual. Because of the rarity and peculiarity, pancreatic lesions from RCC metastasis were described mostly in case reports which highlight the importance of a systematic analysis of this clinical condition. DATA SOURCES: Data of 7 patients with pancreatic metastasis of RCC treated in the Peking Union Medical College Hospital were extracted and 193 similar patients reported in the past 10 years from the literature were analyzed. Epidemiological, pathological and follow-up information were investigated. Potential prognostic factors were compared with corresponding data reported 10 years ago. RESULTS: Multivariate Cox regression showed that asymptomatic metastasis and surgical procedure were independent factors associated with better survival. Compared with the data reported 10 years ago, follow-up of RCC patients has been emphasized in recent years, and atypical surgery is frequently used since it has similar effect as typical surgery on tumor resection while it is able to preserve more pancreatic function. CONCLUSION: Surgical treatment should be an option as long as the pancreatic metastasis of RCC is resectable. PMID- 26818542 TI - Low skeletal muscle mass is associated with non-alcoholic fatty liver disease in Korean adults: the Fifth Korea National Health and Nutrition Examination Survey. AB - BACKGROUND: Sarcopenia and non-alcoholic fatty liver disease (NAFLD) share similar pathophysiological mechanisms, and the relationship between sarcopenia and NAFLD has been recently investigated. The study investigated whether low skeletal muscle mass is differentially associated with NAFLD by gender in Korean adults. METHODS: We conducted a cross-sectional analysis of the data from the Fifth Korea National Health and Nutrition Examination Survey. The skeletal muscle index (SMI) was obtained by the appendicular skeletal muscle mass divided by the weight. NAFLD was defined as a fatty liver index (FLI) >=60 in the absence of other chronic liver disease. RESULTS: Among the included subjects, 18.3% (SE: 1.4%) in men and 7.0% (SE: 0.7%) in women were classified as having FLI-defined NAFLD. Most of the risk factors for FLI-defined NAFLD showed a significant negative correlation with the SMI in both genders. Multiple logistic regression analysis showed that low SMI was associated with FLI-defined NAFLD, independent of other metabolic and lifestyle parameters in both genders [males: odds ratio (OR)=1.35; 95% confidence interval (CI): 1.17-1.54; females: OR=1.36; 95% CI: 1.18-1.55]. The magnitude of the association between FLI-defined NAFLD and low SMI was higher in middle aged to elderly males (OR=1.50; 95% CI: 1.22-1.84) than in males less than 45 years of age (OR=1.25; 95% CI: 1.02-1.52) and in premenopausal females (OR=1.50; 95% CI: 1.12-2.03) than in postmenopausal females (OR=1.36; 95% CI: 1.20-1.54). CONCLUSIONS: Low SMI is associated with the risk of FLI-defined NAFLD independent of other well-known metabolic risk factors in both genders. This association may differ according to age group or menopausal status. Further studies are warranted to confirm this relationship. PMID- 26818543 TI - Ultrasound features of hepatocellular adenoma and the additional value of contrast-enhanced ultrasound. AB - BACKGROUND: Hepatocellular adenoma (HCA) is a rare benign tumor of the liver. It is of clinical importance to differentiate HCA from other liver tumors, especially hepatocellular carcinoma (HCC). This study aimed to evaluate the characteristic features of HCA by conventional ultrasound and contrast-enhanced ultrasound (CEUS) findings. METHODS: Twenty-six patients (10 males and 16 females; mean age 36.2+/-5.0 years) with 26 histopathologically proven HCAs were retrospectively identified. According to the maximum diameter of HCAs, they were divided into three groups: <30 mm, 30-50 mm, and >50 mm. Ultrasound examinations were performed with C5-2 broadband curved transducer of Philips iU22 unit (Philips Bothell, WA, USA). For each lesion, a dose of 2.4 mL SonoVue(r) (Bracco Imaging Spa, Milan, Italy) was injected as a quick bolus into the cubital vein. Lesions' echogenicity, color-Doppler flow imaging and contrast enhancement patterns were recorded. RESULTS: Grayscale ultrasound revealed that most of HCAs were hypoechoic (73.1%, 19/26). Spotty calcifications were detected in 26.9% (7/26) of the lesions. Color-Doppler flow imaging detected centripetal bulky color flow in 46.2% (12/26) of the HCAs. CEUS showed that 73.1% (19/26) of the HCAs displayed as rapid, complete and homogenous enhancement, and 53.8% (14/26) showed decreased contrast enhancement in the late phase. There was no significant difference in enhancement patterns among different sizes of HCAs (P>0.05). Centripetal enhancement with subcapsular tortuous arteries was common in larger HCAs. CONCLUSIONS: CEUS combined with grayscale and color-Doppler flow imaging helped to improve preoperative diagnosis of HCAs. The characteristic imaging features of HCAs included: rapid homogeneous enhancement and slow wash-out pattern on CEUS; heterogeneous echogenicity on grayscale ultrasound; and centripetal enhancement with subcapsular tortuous arteries in large HCAs. PMID- 26818544 TI - CD4+CXCR5+ T cells activate CD27+IgG+ B cells via IL-21 in patients with hepatitis C virus infection. AB - BACKGROUND: Chronic hepatitis C virus (HCV) infection causes the skewing and activation of B cell subsets, but the characteristics of IgG+ B cells in patients with chronic hepatitis C (CHC) infection have not been thoroughly elucidated. CD4+CXCR5+ follicular helper T (Tfh) cells, via interleukin (IL)-21 secretion, activate B cells. However, the role of CD4+CXCR5+ T cells in the activation of IgG+ B cells in CHC patients is not clear. METHODS: The frequency of IgG+ B cells, including CD27-IgG+ B and CD27+IgG+ B cells, the expression of the activation markers (CD86 and CD95) in IgG+ B cells, and the percentage of circulating CD4+CXCR5+ T cells were detected by flow cytometry in CHC patients (n=70) and healthy controls (n=25). The concentrations of serum IL-21 were analyzed using ELISA. The role of CD4+CXCR5+ T cells in the activation of IgG+ B cells was investigated using a co-culture system. RESULTS: A significantly lower proportion of CD27+IgG+ B cells with increased expression of CD86 and CD95 was observed in CHC patients. The expression of CD95 was negatively correlated with the percentage of CD27+IgG+ B cells, and it contributed to CD27+IgG+ B cell apoptosis. Circulating CD4+CXCR5+ T cells and serum IL-21 were significantly increased in CHC patients. Moreover, circulating CD4+CXCR5+ T cells from CHC patients induced higher expressions of CD86 and CD95 in CD27+IgG+ B cells in a co culture system; the blockade of the IL-21 decreased the expression levels of CD86 and CD95 in CD27+IgG+ B cells. CONCLUSIONS: HCV infection increased the frequency of CD4+CXCR5+ T cells and decreased the frequency of CD27+IgG+ B cells. CD4+CXCR5+ T cells activated CD27+IgG+ B cells via the secretion of IL-21. PMID- 26818545 TI - miR-26a regulates mouse hepatocyte proliferation via directly targeting the 3' untranslated region of CCND2 and CCNE2. AB - BACKGROUND: The deficiency of liver regeneration needs to be addressed in the fields of liver surgery, split liver transplantation and living donor liver transplantation. Researches of microRNAs would broaden our understandings on the mechanisms of various diseases. Our previous research confirmed that miR-26a regulated liver regeneration in mice; however, the relationship between miR-26a and its target, directly or indirectly, remains unclear. Therefore, the present study further investigated the mechanism of miR-26a in regulating mouse hepatocyte proliferation. METHODS: An established mouse liver cell line, Nctc 1469, was transfected with Ad5-miR-26a-EGFP, Ad5-anti-miR-26a-EGFP or Ad5-EGFP vector. Cell proliferation was assessed by MTS, cell apoptosis and cell cycle by flow cytometry, and gene expression by Western blotting and quantitative real time PCR. Dual-luciferase reporter assays were used to test targets of miR-26a. RESULTS: Compared with the Ad5-EGFP group, Ad5-anti-miR-26a-EGFP down-regulated miR-26a and increased proliferation of hepatocytes, with more cells entering the G1 phase of cell cycle (82.70%+/-1.45% vs 75.80%+/-3.92%), and decreased apoptosis (5.50%+/-0.35% vs 6.73%+/-0.42%). CCND2 and CCNE2 were the direct targeted genes of miR-26a. miR-26a down-regulation up-regulated CCND2 and CCNE2 expressions and down-regulated p53 expression in Nctc-1469 cells. On the contrary, miR-26a over-expression showed the opposite results. CONCLUSIONS: miR 26a regulated mouse hepatocyte proliferation by directly targeting the 3' untranslated regions of cyclin D2/cyclin E2; miR-26a also regulated p53-mediated apoptosis. Our data suggested that miR-26a may be a promising regulator in liver regeneration. PMID- 26818546 TI - The therapeutic effect of CORM-3 on acute liver failure induced by lipopolysaccharide/D-galactosamine in mice. AB - BACKGROUND: Acute liver failure (ALF) is a severe and life-threatening clinical syndrome resulting in a high mortality and extremely poor prognosis. Recently, a water-soluble CO-releasing molecule (CORM-3) has been shown to have anti inflammatory effect. The present study was to investigate the effect of CORM-3 on ALF and elucidate its underlying mechanism. METHODS: ALF was induced by a combination of LPS/D-GalN in mice which were treated with CORM-3 or inactive CORM 3 (iCORM-3). The efficacy of CORM-3 was evaluated based on survival, liver histopathology, serum aminotransferase activities (ALT and AST) and total bilirubin (TBiL). Serum levels of inflammatory cytokines (TNF-alpha, IL-6, IL 1beta and IL-10) and liver immunohistochemistry of NF-kappaB-p65 were determined; the expression of inflammatory mediators such as iNOS, COX-2 and TLR4 was measured using Western blotting. RESULTS: The pretreatment with CORM-3 significantly improved the liver histology and the survival rate of mice compared with the controls; CORM-3 also decreased the levels of ALT, AST and TBiL. Furthermore, CORM-3 significantly inhibited the increased concentration of pro inflammatory cytokines (TNF-alpha, IL-6 and IL-1beta) and increased the anti inflammatory cytokine (IL-10) productions in ALF mice. Moreover, CORM-3 significantly reduced the increased expression of iNOS and TLR4 in liver tissues and inhibited the nuclear expression of NF-kappaB-p65. CORM-3 had no effect on the increased expression of COX-2 in the ALF mice. An iCORM-3 failed to prevent acute liver damage induced by LPS/D-GalN. CONCLUSION: These findings provided evidence that CORM-3 may offer a novel alternative approach for the management of ALF through anti-inflammatory functions. PMID- 26818547 TI - Risk factors for postoperative bile leakage: a retrospective single-center analysis of 411 hepatectomies. AB - BACKGROUND: The primary focus of the study was to analyze the risk factors for bile leakage after hepatectomy for benign or malignant tumors. METHODS: A total of 411 patients who had undergone hepatectomy between December 2006 and December 2011 were retrospectively analyzed. The severity of bile leakage was graded according to the ISGLS classification. Twenty-eight pre- and postoperative parameters were analyzed. RESULTS: The overall bile leakage incidence was 10.2% (42/411). The severity of the leakage was classified according to the ISGLS classification. Bile leakage was detected early in case of abdominal drainage (11.4% vs 1.9%, P=0.034). It prolonged the time of hospitalization (16 vs 9 days, P=0.001). In all patients, wedge resection was associated with a higher incidence of bile leakage in contrast to anatomical resections (25.6% vs 4.1%, P<0.0001) regardless of the underlying liver disease. Furthermore, total vascular exclusion increased risk of bile leakage (P=0.008). CONCLUSIONS: Bile leakage as a major issue after hepatic resection is related to the postoperative morbidity and the hospitalization time. It is associated with non-anatomical resection and a total vascular exclusion. PMID- 26818549 TI - Acute pancreatitis induced by transarterial chemoembolization: a single-center experience of over 1500 cases. AB - BACKGROUND: Acute pancreatitis is a relatively rare but potentially lethal complication after transarterial chemotherapy. This study aimed to review the complications such as acute pancreatitis after transarterial chemotherapy with or without embolization for hepatocellular carcinoma. METHODS: A total of 1632 patients with hepatocellular carcinoma who had undergone transarterial chemoembolization from January 2000 to February 2014 in a single-center were reviewed retrospectively. We investigated the potential complications of transarterial chemoembolization, such as acute pancreatitis and acute pancreatitis-related complications. RESULTS: Of the 1632 patients with hepatocellular carcinoma who had undergone 5434 transarterial chemoembolizations, 1328 were male and 304 female. The median age of these patients was 61 years. Most (79.6%) of the patients suffered from HBV-related hepatocellular carcinoma. The median tumor size was 5.2 cm. Of the 1632 patients, 145 patients underwent transarterial chemoembolization with doxorubicin eluting bead, making up a total of 538 episodes. The remaining patients underwent transarterial chemoembolization with cisplatin. Seven (0.4%) patients suffered from acute pancreatitis post chemoembolization. Six patients had chemoembolization with doxorubicin and one had chemoembolization with cisplatin. Patients who received doxorubicin eluting bead had a higher risk of acute pancreatitis [6/145 (4.1%) vs 1/1487 (0.1%), P<0.0001]. Two patients had anatomical arterial variations. Four patients developed acute pancreatitis-related complications including necrotizing pancreatitis (n=3) and pseudocyst formation (n=1). All of the 4 patients resolved after the use of antibiotics and other conservative treatment. Three patients had further transarterial chemoembolization without any complication. CONCLUSIONS: Acute pancreatitis after transarterial chemoembolization could result in serious complications, especially after treatment with doxorubicin eluting bead. Continuation of current treatment with transarterial chemoembolization after acute pancreatitis is feasible providing the initial attack is completely resolved. PMID- 26818548 TI - Silver-nanoparticle-coated biliary stent inhibits bacterial adhesion in bacterial cholangitis in swine. AB - BACKGROUND: One of the major limitations of biliary stents is the stent occlusion, which is closely related to the over-growth of bacteria. This study aimed to evaluate the feasibility of a novel silver-nanoparticle-coated polyurethane (Ag/PU) stent in bacterial cholangitis model in swine. METHODS: Ag/PU was designed by coating silver nanoparticles on polyurethane (PU) stent. Twenty-four healthy pigs with bacterial cholangitis using Ag/PU and PU stents were randomly divided into an Ag/PU stent group (n=12) and a PU stent group (n=12), respectively. The stents were inserted by standard endoscopic retrograde cholangiopancreatography. Laboratory assay was performed for white blood cell (WBC) count, alanine aminotransferase (ALT), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) at baseline time, 8 hours, 1, 2, 3, and 7 days after stent placements. The segment of bile duct containing the stent was examined histologically ex vivo. Implanted biliary stents were examined by a scan electron microscope. The amount of silver release was also measured in vitro. RESULTS: The number of inflammatory cells and level of ALT, IL-1beta and TNF alpha were significantly lower in the Ag/PU stent group than in the PU stent group. Hyperplasia of the mucosa was more severe in the PU stent group than in the Ag/PU stent group. In contrast to the biofilm of bacteria on the PU stent, fewer bacteria adhered to the Ag/PU stent. CONCLUSIONS: PU biliary stents modified with silver nanoparticles are able to alleviate the inflammation of pigs with bacterial cholangitis. Silver-nanoparticle-coated stents are resistant to bacterial adhesion. PMID- 26818550 TI - Circulating myeloid-derived suppressor cells in patients with pancreatic cancer. AB - BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are heterogeneous cell types that suppress T-cell responses in cancer patients and animal models, some MDSC subpopulations are increased in patients with pancreatic cancer. The present study was to investigate a specific subset of MDSCs in patients with pancreatic cancer and the mechanism of MDSCs increase in these patients. METHODS: Myeloid cells from whole blood were collected from 37 patients with pancreatic cancer, 17 with cholangiocarcinoma, and 47 healthy controls. Four pancreatic cancer cell lines were co-cultured with normal peripheral blood mononuclear cells (PBMCs) to test the effect of tumor cells on the conversion of PBMCs to MDSCs. Levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and arginase activity in the plasma of cancer patients were analyzed by enzyme-linked immunosorbent assay. RESULTS: CD14+/CD11b+/HLA-DR- MDSCs were increased in patients with pancreatic or bile duct cancer compared with those in healthy controls, and this increase was correlated with clinical cancer stage. Pancreatic cancer cell lines induced PBMCs to MDSCs in a dose-dependent manner. GM-CSF and arginase activity levels were significantly increased in the serum of patients with pancreatic cancer. CONCLUSIONS: MDSCs were tumor related: tumor cells induced PBMCs to MDSCs in a dose-dependent manner and circulating CD14+/CD11b+/HLA-DR- MDSCs in pancreatic cancer patients were positively correlated with tumor burden. MDSCs might be useful markers for pancreatic cancer detection and progression. PMID- 26818551 TI - Successful liver allograft inflow reconstruction with the right gastroepiploic vein. AB - Portal vein thrombosis is a common complication in cirrhotic patients. When portal vein thrombectomy is not a suitable option, a large collateral vessel can be used for allograft venous inflow reconstruction. We describe an unusual case of successful portal revascularization using the right gastroepiploic vein. The patient underwent a cadaveric orthotopic liver transplantation with end-to-end anastomosis of the portal vein to the right gastroepiploic vein. Six months after liver transplantation the patient is well with good liver function. The use of the right gastroepiploic vein for allograft venous reconstruction is feasible and safe, with a great advantage of avoiding the need of venous jump graft. PMID- 26818552 TI - External validation of PREPARE score in Turkish patients who underwent pancreatic surgery. PMID- 26818553 TI - The Author Reply. PMID- 26818554 TI - SLAP lesions: a treatment algorithm. AB - Tears of the superior labrum involving the biceps anchor are a common entity, especially in athletes, and may highly impair shoulder function. If conservative treatment fails, successful arthroscopic repair of symptomatic SLAP lesions has been described in the literature particularly for young athletes. However, the results in throwing athletes are less successful with a significant amount of patients who will not regain their pre-injury level of performance. The clinical results of SLAP repairs in middle-aged and older patients are mixed, with worse results and higher revision rates as compared to younger patients. In this population, tenotomy or tenodesis of the biceps tendon is a viable alternative to SLAP repairs in order to improve clinical outcomes. The present article introduces a treatment algorithm for SLAP lesions based upon the recent literature as well as the authors' clinical experience. The type of lesion, age of patient, concomitant lesions, and functional requirements, as well as sport activity level of the patient, need to be considered. Moreover, normal variations and degenerative changes in the SLAP complex have to be distinguished from "true" SLAP lesions in order to improve results and avoid overtreatment. The suggestion for a treatment algorithm includes: type I: conservative treatment or arthroscopic debridement, type II: SLAP repair or biceps tenotomy/tenodesis, type III: resection of the instable bucket-handle tear, type IV: SLAP repair (biceps tenotomy/tenodesis if >50 % of biceps tendon is affected), type V: Bankart repair and SLAP repair, type VI: resection of the flap and SLAP repair, and type VII: refixation of the anterosuperior labrum and SLAP repair. PMID- 26818555 TI - Femoral interference screw fixation of hamstring and quadriceps tendons for ACL reconstruction. AB - PURPOSE: This cadaveric study compares the biomechanical properties of femoral graft fixation in ACL reconstruction of either quadriceps or hamstring tendon grafts with four different interference screws. The hypothesis was that quadriceps tendon grafts provide at least equal results concerning gap formation during cyclic loading and ultimate failure load compared to hamstring tendon grafts with four different interference screws. METHODS: Eighty porcine femora underwent interference screw fixation of human tendon grafts for ACL reconstruction. Either quadriceps (Q) or hamstring (H) tendon grafts and four different bioabsorbable interference (Wolf (W), Storz (S), Mitek (M), Arthrex (A)) screws were used, resulting in 8 groups with 10 specimens per groups (WQ, WH, SQ, SH, MQ, MH, AQ, AH). Biomechanical analysis included pretensioning the constructs with 60 N for 30 s, then cyclic loading of 500 cycles between 60 and 250 N at 1 Hz in a servohydraulic testing machine, with measurement of elongation and stiffness including video measurements. After this, ultimate failure load and failure mode analysis were performed. RESULTS: No statistically significant difference could be noted between the groups regarding gap formation during cyclic loading [Cycles 21-500 (mm): WQ 3.6 +/- 0.8, WH 3.9 +/- 1.4, SQ 3.6 +/- 0.8, SH 3.3 +/- 1.5, MQ 4.3 +/- 0.8, MH 4.6 +/- 1.0, AQ 4.8 +/- 0.8, AH 4.3 +/- 1.5, n.s.], stiffness during cyclic loading [Cycles 21-500 (N/mm): WQ 72.9 +/- 16.9, WH 71.6 +/- 20.7, SQ 69.5 +/- 23.9, SH 77.4 +/- 25.1, MQ 59.6 +/- 11.2, MH 48.4 +/- 15.4, AQ 48.8 +/- 12.7, AH 51.9 +/- 22.2, n.s.], and ultimate failure load [(N): WQ 474.4 +/- 88.0, WH 579.3 +/- 124.2, SQ 493.9 +/- 105.2, SH 576.0 +/ 90.4, MQ 478.6 +/- 59.0, MH 543.9 +/- 119.7, AQ 480.2 +/- 93.8, AH 497.8 +/- 74.2, n.s.]. CONCLUSIONS: Quadriceps tendon grafts yield comparable biomechanical results for femoral interference screw fixation in ACL reconstruction compared to hamstring tendon grafts. From a clinical perspective, quadriceps tendon grafts should therefore be considered as a good option in ACL reconstruction in the future. PMID- 26818557 TI - Calcium Deposits in the Crayfish, Cherax quadricarinatus: Microstructure Versus Elemental Distribution. AB - The crayfish Cherax quadricarinatus stores calcium ions, easily mobilizable after molting, for calcifying parts of the new exoskeleton. They are chiefly stored as amorphous calcium carbonate (ACC) during each premolt in a pair of gastroliths synthesized in the stomach wall. How calcium carbonate is stabilized in the amorphous state in such a biocomposite remains speculative. The knowledge of the microstructure at the nanometer level obtained by field emission scanning electron microscopy and atomic force microscopy combined with scanning electron microscopy energy-dispersive X-ray spectroscopy, micro-Raman and X-ray absorption near edge structure spectroscopy gave relevant information on the elaboration of such an ACC-stabilized biomineral. We observed nanogranules distributed along chitin-protein fibers and the aggregation of granules in thin layers. AFM confirmed the nanolevel structure, showing granules probably surrounded by an organic layer and also revealing a second level of aggregation as described for other crystalline biominerals. Raman analyses showed the presence of ACC, amorphous calcium phosphate, and calcite. Elemental analyses confirmed the presence of elements like Fe, Na, Mg, P, and S. P and S are heterogeneously distributed. P is present in both the mineral and organic phases of gastroliths. S seems present as sulfate (probably as sulfated sugars), sulfonate, sulfite, and sulfoxide groups and, in a lesser extent, as sulfur-containing amino acids. PMID- 26818556 TI - The diagnostic application of RNA sequencing in patients with thyroid cancer: an analysis of 851 variants and 133 fusions in 524 genes. AB - BACKGROUND: Thyroid carcinomas are known to harbor oncogenic driver mutations and advances in sequencing technology now allow the detection of these in fine needle aspiration biopsies (FNA). Recent work by The Cancer Genome Atlas (TCGA) Research Network has expanded the number of genetic alterations detected in papillary thyroid carcinomas (PTC). We sought to investigate the prevalence of these and other genetic alterations in diverse subtypes of thyroid nodules beyond PTC, including a variety of samples with benign histopathology. This is the first clinical evaluation of a large panel of TCGA-reported genomic alterations in thyroid FNAs. RESULTS: In FNAs, genetic alterations were detected in 19/44 malignant samples (43% sensitivity) and in 7/44 histopathology benign samples (84% specificity). Overall, after adding a cohort of tissue samples, 38/76 (50%) of histopathology malignant samples were found to harbor a genetic alteration, while 15/75 (20%) of benign samples were also mutated. The most frequently mutated malignant subtypes were medullary thyroid carcinoma (9/12, 75%) and PTC (14/30, 47%). Additionally, follicular adenoma, a benign subtype of thyroid neoplasm, was also found to harbor mutations (12/29, 41%). Frequently mutated genes in malignant samples included BRAF (20/76, 26%) and RAS (9/76, 12%). Of the TSHR variants detected, (6/7, 86%) were in benign nodules. In a direct comparison of the same FNA also tested by an RNA-based gene expression classifier (GEC), the sensitivity of genetic alterations alone was 42%, compared to the 91% sensitivity achieved by the GEC. The specificity based only on genetic alterations was 84%, compared to 77% specificity with the GEC. CONCLUSIONS: While the genomic landscape of all thyroid neoplasm subtypes will inevitably be elucidated, caution should be used in the early adoption of published mutations as the sole predictor of malignancy in thyroid. The largest set of such mutations known to date detects only a portion of thyroid carcinomas in preoperative FNAs in our cohort and thus is not sufficient to rule out cancer. Due to the finding that variants are also found in benign nodules, testing only GEC suspicious nodules may be helpful in avoiding false positives and altering the extent of treatment when selected mutations are found. PMID- 26818559 TI - Extravascular Lung Water Index as a Predictive Factor For Non-invasive Ventilation Failure. The Last Chance to Make the Right Decision? PMID- 26818560 TI - Robin Ferner: A weakness for bad jokes. PMID- 26818558 TI - Counterintuitive Pulmonary Nodules in Rheumatoid Arthritis. PMID- 26818561 TI - Balancing Innovation and Value of Biological Meshes in Hernia: Who Is in Charge? PMID- 26818563 TI - Automated analysis of food-borne pathogens using a novel microbial cell culture, sensing and classification system. AB - We hereby report the design and implementation of an Autonomous Microbial Cell Culture and Classification (AMC(3)) system for rapid detection of food pathogens. Traditional food testing methods require multistep procedures and long incubation period, and are thus prone to human error. AMC(3) introduces a "one click approach" to the detection and classification of pathogenic bacteria. Once the cultured materials are prepared, all operations are automatic. AMC(3) is an integrated sensor array platform in a microbial fuel cell system composed of a multi-potentiostat, an automated data collection system (Python program, Yocto Maxi-coupler electromechanical relay module) and a powerful classification program. The classification scheme consists of Probabilistic Neural Network (PNN), Support Vector Machines (SVM) and General Regression Neural Network (GRNN) oracle-based system. Differential Pulse Voltammetry (DPV) is performed on standard samples or unknown samples. Then, using preset feature extractions and quality control, accepted data are analyzed by the intelligent classification system. In a typical use, thirty-two extracted features were analyzed to correctly classify the following pathogens: Escherichia coli ATCC#25922, Escherichia coli ATCC#11775, and Staphylococcus epidermidis ATCC#12228. 85.4% accuracy range was recorded for unknown samples, and within a shorter time period than the industry standard of 24 hours. PMID- 26818564 TI - Immobilization of Stimuli-Responsive Nanogels onto Honeycomb Porous Surfaces and Controlled Release of Proteins. AB - In this article, we describe the formation of functional honeycomb-like porous surfaces fabricated by the breath figures technique using blends of either amino terminated poly(styrene) or a poly(styrene)-b-poly(acrylic acid) block copolymer with homopoly(styrene). Thus, the porous interfaces exhibited either amino or acid groups selectively located inside of the holes, which were subsequently employed to anchor stimuli-responsive nanogels by electrostatic interactions. These nanogels were prepared from poly(N-isopropylacrylamide) (PNIPAM) cross linked with dendritic polyglycerol (dPG) and semi-interpenetrated with either 2 (dimethylamino)ethyl methacrylate (DMAEMA) or 2-acrylamido-2-methyl-1 propanesulfonic acid (AMPS) to produce positively and negatively charged nanogel surfaces, respectively. The immobilization of these semi-interpenetrated networks onto the surfaces allowed us to have unique stimuli-responsive surfaces with both controlled topography and composition. More interestingly, the surfaces exhibited stimuli-responsive behavior by variations on the pH or temperature. Finally, the surfaces were evaluated regarding their capacity to induce a thermally triggered protein release at temperatures above the cloud point temperature (T(cp)) of the nanogels. PMID- 26818562 TI - Bacterial GCN5-Related N-Acetyltransferases: From Resistance to Regulation. AB - The GCN5-related N-acetyltransferases family (GNAT) is an important family of proteins that includes more than 100000 members among eukaryotes and prokaryotes. Acetylation appears as a major regulatory post-translational modification and is as widespread as phosphorylation. N-Acetyltransferases transfer an acetyl group from acetyl-CoA to a large array of substrates, from small molecules such as aminoglycoside antibiotics to macromolecules. Acetylation of proteins can occur at two different positions, either at the amino-terminal end (alphaN-acetylation) or at the epsilon-amino group (epsilonN-acetylation) of an internal lysine residue. GNAT members have been classified into different groups on the basis of their substrate specificity, and in spite of a very low primary sequence identity, GNAT proteins display a common and conserved fold. This Current Topic reviews the different classes of bacterial GNAT proteins, their functions, their structural characteristics, and their mechanism of action. PMID- 26818565 TI - Cellular microenvironment controls the nuclear architecture of breast epithelia through beta1-integrin. AB - Defects in nuclear architecture occur in a variety of diseases, however the fundamental mechanisms that control the internal structure of nuclei are poorly defined. Here we reveal that the cellular microenvironment has a profound influence on the global internal organization of nuclei in breast epithelia. A 3D microenvironment induces a prolonged but reversible form of cell cycle arrest that features many of the classical markers of cell senescence. This unique form of arrest is dependent on signaling from the external microenvironment through beta1-integrins. It is concomitant with alterations in nuclear architecture that characterize the withdrawal from cell proliferation. Unexpectedly, following prolonged cell cycle arrest in 3D, the senescence-like state and associated reprogramming of nuclear architecture are freely reversible on altering the dimensionality of the cellular microenvironment. Breast epithelia can therefore maintain a proliferative plasticity that correlates with nuclear remodelling. However, the changes in nuclear architecture are cell lineage-specific and do not occur in fibroblasts, and moreover they are overcome in breast cancer cells. PMID- 26818566 TI - The interaction between artemether-lumefantrine and lopinavir/ritonavir-based antiretroviral therapy in HIV-1 infected patients. AB - BACKGROUND: Artemether-lumefantrine is currently the most widely recommended treatment of uncomplicated malaria. Lopinavir-based antiretroviral therapy is the commonly recommended second-line HIV treatment. Artemether and lumefantrine are metabolised by cytochrome P450 isoenzyme CYP3A4, which lopinavir/ritonavir inhibits, potentially causing clinically important drug-drug interactions. METHODS: An adaptive, parallel-design safety and pharmacokinetic study was conducted in HIV-infected (malaria-negative) patients: antiretroviral-naive and those stable on lopinavir/ritonavir-based antiretrovirals. Both groups received the recommended six-dose artemether-lumefantrine treatment. The primary outcome was day-7 lumefantrine concentrations, as these correlate with antimalarial efficacy. Adverse events were solicited throughout the study, recording the onset, duration, severity, and relationship to artemether-lumefantrine. RESULTS: We enrolled 34 patients. Median day-7 lumefantrine concentrations were almost 10 fold higher in the lopinavir than the antiretroviral-naive group [3170 versus 336 ng/mL; p = 0.0001], with AUC(0-inf) and Cmax increased five-fold [2478 versus 445 MUg.h/mL; p = 0.0001], and three-fold [28.2 versus 8.8 MUg/mL; p < 0.0001], respectively. Lumefantrine Cmax, and AUC(0-inf) increased significantly with mg/kg dose in the lopinavir, but not the antiretroviral-naive group. While artemether exposure was similar between groups, Cmax and AUC(0-8h) of its active metabolite dihydroartemisinin were initially two-fold higher in the lopinavir group [p = 0.004 and p = 0.0013, respectively]. However, this difference was no longer apparent after the last artemether-lumefantrine dose. Within 21 days of starting artemether-lumefantrine there were similar numbers of treatment emergent adverse events (42 vs. 35) and adverse reactions (12 vs. 15, p = 0.21) in the lopinavir and antiretroviral-naive groups, respectively. There were no serious adverse events and no difference in electrocardiographic QTcF- and PR-intervals, at the predicted lumefantrine Tmax. CONCLUSION: Despite substantially higher lumefantrine exposure, intensive monitoring in our relatively small study raised no safety concerns in HIV-infected patients stable on lopinavir-based antiretroviral therapy given the recommended artemether-lumefantrine dosage. Increased day-7 lumefantrine concentrations have been shown previously to reduce the risk of malaria treatment failure, but further evidence in adult patients co infected with malaria and HIV is needed to assess the artemether-lumefantrine risk : benefit profile in this vulnerable population fully. Our antiretroviral naive patients confirmed previous findings that lumefantrine absorption is almost saturated at currently recommended doses, but this dose-limited absorption was overcome in the lopinavir group. TRIAL REGISTRATION: Clinical Trial Registration number NCT00869700. Registered on clinicaltrials.gov 25 March 2009. PMID- 26818567 TI - Delayed luminescence: an experimental protocol for Chinese herbal medicines. AB - In Chinese medicine, raw herbal materials are used in processed and unprocessed forms aiming to meet the different requirements of clinical practice. To assure the chemical quality and therapeutic properties of the herbs, fast and integrated systematic assays are required. So far, such assays have not been established. Delayed luminescence (DL) refers to a decaying long-term ultraweak photon emission after exposure to light. Its decay kinetics under certain conditions may be a sensitive indicator reflecting the internal structural and chemical/physiological state of a biological system. DL measurements have been used in many applications for quality control. However, relatively little research has been reported on dried plant material such as Chinese herbs. The objective of the present study is to establish a protocol for direct and rapid DL measurements of dried Chinese herbal materials, including the determination of the dependence on: (a) the optimal excitation time utilizing a white light source; (b) the optimal size of the grinded herbal particle; and (c) the humidity conditions before and during measurement. Results indicate that stable and reproducible curves of DL photon emission depend mainly on the water content of herbal materials. To investigate the application of the established DL measurement protocol, non-processed and processed Aconitum (Aconitum carmichaelii Debx.), wild and cultivated rhubarb (Rheum palmatum L.) and ginseng (Panax ginseng C.A.Mey) of different ages were measured using DL. The results suggest that DL technology is a potential tool for assessment of dried Chinese herb qualities. The results warrant a further exploration of this technique in relation to therapeutic properties of the herbs. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26818568 TI - From a paper-based to a web-based Journal. PMID- 26818569 TI - Ellis-van Creveld syndrome associated with chronic intestinal pseudo-obstruction. AB - Ellis-van Creveld (EVC) syndrome is a rare autosomal recessive disorder characterized by hypoplastic nails, polydactyly, and achondroplasia. Patients usually exhibit normal cognitive function and no remarkable developmental delay. We herein present an unusual case of EVC syndrome. A Japanese 2-year-old boy was born at term, but immediately developed severe respiratory failure due to thorax deformity, postaxial polydactyly and nail hypoplasia. We identified a novel pattern of germinal compound heterozygous nonsense EVC2 mutations of c.1814C > A (p. S605X) and c.2653C > T (p. R885X), leading to the diagnosis of EVC syndrome. Interestingly, he also had severe developmental delay, and suddenly developed excessive abdominal distension at the age of 2. On surgery, extensive necrotic bowel with chronic intestinal pseudo-obstruction was noted. This is, to our knowledge, a most severe phenotype of EVC syndrome, illustrating that the specific pattern of EVC2 compound heterozygous mutations may cause severe developmental delay and intestinal malfunction. PMID- 26818571 TI - Treatment of the older adult with ALL: An urgent call to action. PMID- 26818572 TI - Targeting B-cell non Hodgkin lymphoma: New and old tricks. AB - The management of B-cell malignancies continues to pose a clinical challenge. In the past years, rituximab (anti-CD20) emerged as the standard of care in the induction treatment of follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), and mantle cell lymphoma (MCL), as well as in other subsets. Since the benefits of immuno-chemotherapy have been clearly demonstrated in a whole range of lymphomas, several innovative approaches are being explored to achieve significant responses, particularly in refractory B cell non-Hodgkin lymphoma (NHL) cases. Studies of the comparative effectiveness and structure/function relationship of therapeutic monoclonal antibodies, together with an increased understanding of the molecular features of NHLs, have led to the development of a range of novel therapies, many of which target the tumor in a tailored fashion. Although several molecules can help clinicians to dissect the pathological mechanisms acting in the natural history of the disease, the main purpose of this review emphasize the recent developments in targeting the B-cell NHLs surface. These novel approaches are illustrated, and the new intriguing opportunities offered by bispecific antibodies and antibody-associated immune modulation are addressed. PMID- 26818574 TI - Niemann-Pick disease type C1(NPC1) is involved in resistance against imatinib in the imatinib-resistant Ph+ acute lymphoblastic leukemia cell line SUP-B15/RI. AB - Niemann-Pick disease type C1 (NPC1) is involved in cholesterol trafficking and may normally function as a transmembrane efflux pump. Previous studies showed that its dysfunction can lead to cholesterol and daunorubicin accumulation in the cytoplasmic endosomal/lysosomal system, lead to Niemann-Pick disease and resistance to anticancer drugs. In the present study, NPC1 was shown by microarray analysis to be more highly expressed in the Ph+ acute lymphoblastic leukemia cell line SUP-B15/RI, an imatinib-resistant variant of SUP-B15/S cells without bcr-abl gene mutation established in our lab. Further investigation revealed a defect in the functional capacity of the NPC1 protein demonstrated by filipin staining accompanied by a lower intracellular imatinib mesylate(IM) concentration by high-performance liquid chromatography in SUP-B15/RI compared with SUP-B15/S cells. Furthermore, U18666A, an inhibitor of NPC1 function, was used to block cholesterol trafficking to imitate the NPC1 defect in SUP-B15/S cells, leading to higher NPC1 expression, stronger filipin fluorescence, lower intracellular IM concentrations and greater resistance against IM. Samples from non-mutated relapsed Ph+ ALL patients also showed higher NPC1 expression compared with IM-sensitive patients. Our experiment may reveal a new mechanism of IM resistance in Ph+ ALL. PMID- 26818575 TI - Divergent variations in concentrations of chemical elements among shrub organs in a temperate desert. AB - Desert shrubs, a dominant component of desert ecosystems, need to maintain sufficient levels of nutrients in their different organs to ensure operation of various physiological functions for the purpose of survival and reproduction. In the present study, we analyzed 10 elements in leaves, stems, and roots of 24 dominant shrub species from 52 sites across a temperate desert ecosystem in northwestern China. We found that concentrations of all 10 elements were higher in leaves than in stems and roots, that non-legumes had higher levels of leaf Na and Mg than did legumes, and that Na was more concentrated in C4 leaves than in C3 leaves. Scaling relationships of elements between the photosynthetic organ (leaf) and non-photosynthetic organs (stem and root) were allometric. Results of principal components analysis (PCA) highlighted the important role of the elements responsible for osmoregulation (K and Na) in water utilization of desert shrubs. Soil properties and taxonomy explained most variation of element concentrations in desert shrubs. Desert shrubs may not be particularly susceptible to future change in climate factors, because most elements (including N, P, K, Ca, Mn, Zn, and Cu) associated with photosynthesis, osmoregulation, enzyme activity, and water use efficiency primarily depend on soil conditions. PMID- 26818576 TI - Production of electrically-conductive nanoscale filaments by sulfate-reducing bacteria in the microbial fuel cell. AB - This study reports that the obligate anaerobic microorganism, Desulfovibrio desulfuricans, a predominant sulfate-reducing bacterium (SRB) in soils and sediments, can produce nanoscale bacterial appendages for extracellular electron transfer. These nanofilaments were electrically-conductive (5.81S.m(-1)) and allowed SRBs to directly colonize the surface of insoluble or solid electron acceptors. Thus, the direct extracellular electron transfer to the insoluble electrode in the microbial fuel cell (MFC) was possible without inorganic electron-shuttling mediators. The production of nanofilaments was stimulated when only insoluble electron acceptors were available for cellular respiration. These results suggest that when availability of a soluble electron acceptor for SRBs (SO4(2-)) is limited, D. desulfuricans initiates the production of conductive nanofilaments as an alternative strategy to transfer electrons to insoluble electron acceptors. The findings of this study contribute to understanding of the role of SRBs in the biotransformation of various substances in soils and sediments and in the MFC. PMID- 26818578 TI - Structural characterization of aqueous solution poly(oligo(ethylene oxide) monomethyl methacrylate)-grafted silica nanoparticles. AB - The structure of aqueous dispersions of poly(oligo(ethylene oxide) monomethyl methacrylate)-grafted silica nanoparticles was characterized using contrast variation small-angle neutron scattering studies. Modeling the low hybrid concentration dispersion scattering data using a fuzzy sphere and a polydisperse core-shell model, demonstrated that the polymer chains are highly swollen in the dispersions as compared to the dimensions of the free polymer chains in dilute solution. At higher hybrid concentrations, the dispersions were well described using a Percus-Yevick approximation to describe the structure factor. These structural characterization tools are excellent starting points for effective molecular level descriptors of dewetting and macroscopic phase transitions for polymer tethered hybrid nanoparticle systems. PMID- 26818577 TI - Performance, 5-aminolevulinic acid (ALA) yield and microbial population dynamics in a photobioreactor system treating soybean wastewater: Effect of hydraulic retention time (HRT) and organic loading rate (OLR). AB - Effects of hydraulic retention time (HRT) and influent organic loading rate (OLR) were investigated in a photobioreactor containing PNSB (Rhodobacter sphaeroides) chemoheterotrophic bacteria to treat soybean wastewater. Pollutants removal, biomass production and ALA yield in different phases were investigated in together with functional microbial population dynamics. The results showed that proper HRT and OLR increased the photobioreactor performance including pollutants removal, biomass and ALA productions. 89.5% COD, 90.6% TN and 91.2% TP removals were achieved as well as the highest biomass production of 2655mg/L and ALA yield of 7.40mg/g-biomass under the optimal HRT of 60h and OLR of 2.48g/L/d. In addition, HRT and OLR have important impacts on PNSB and total bacteria dynamics. PMID- 26818579 TI - Probing the thermal stability and the decomposition mechanism of a magnesium fullerene polymer via X-ray Raman spectroscopy, X-ray diffraction and molecular dynamics simulations. AB - We report the microscopic view of the thermal structural stability of the magnesium intercalated fullerene polymer Mg2C60. With the application of X-ray Raman spectroscopy and X-ray diffraction, we study in detail the decomposition pathways of the polymer system upon annealing at temperatures between 300 and 700 degrees C. We show that there are at least two energy scales involved in the decomposition reaction. Intermolecular carbon bonds, which are responsible for the formation of a 2D fullerene polymer, are broken with a relatively modest thermal energy, while the long-range order of the original polymer remains intact. With an increased thermal energy, the crystal structure in turn is found to undergo a transition to a novel intercalated cubic phase that is stable up to the highest temperature studied here. The local structure surrounding magnesium ions gets severely modified close to, possibly at, the phase transition. We used density functional theory based calculations to study the thermodynamic and kinetic aspects of the collapse of the fullerene network, and to explain the intermediate steps as well as the reaction pathways in the break-up of this peculiar C60 intermolecular bonding architecture. PMID- 26818573 TI - Association between early promoter-specific DNA methylation changes and outcome in older acute myeloid leukemia patients. AB - Treatment options for older patients with acute myeloid leukemia (AML) range from supportive care alone to full-dose chemotherapy. Identifying factors that predict response to therapy may help increase efficacy and avoid toxicity. The phase II SWOG S0703 study investigated the use of hydroxyurea and azacitidine with gemtuzumab ozogamicin in the elderly AML population and found survival rates similar to those expected with standard AML regimens, with less toxicity. As part of this study, global DNA methylation along with promoter DNA methylation and expression analysis of six candidate genes (CDKN2A, CDKN2B, HIC1, RARB, CDH1 and APAF1) were determined before and during therapy to investigate whether very early changes are prognostic for clinical response. Global DNA methylation was not associated with a clinical response. Samples after 3 or 4 days of treatment with azacitidine showed significantly decreased CDKN2A promoter DNA methylation in patients achieving complete remission (CR) compared to those who did not. Samples from day 7 of treatment showed significantly decreased RARB, CDKN2B and CDH1 promoter DNA methylation in responders compared to nonresponders. Gene specific DNA methylation analysis of peripheral blood samples may help early identification of those older AML patients most likely to benefit from demethylating agent therapy. PMID- 26818580 TI - Magnetic ground state of an individual Fe(2+) ion in strained semiconductor nanostructure. AB - Single impurities with nonzero spin and multiple ground states offer a degree of freedom that can be utilized to store the quantum information. However, Fe(2+) dopant is known for having a single nondegenerate ground state in the bulk host semiconductors and thus is of little use for spintronic applications. Here we show that the well-established picture of Fe(2+) spin configuration can be modified by subjecting the Fe(2+) ion to high strain, for example, produced by lattice mismatched epitaxial nanostructures. Our analysis reveals that high strain induces qualitative change in the ion energy spectrum and results in nearly doubly degenerate ground state with spin projection Sz= +/- 2. We provide an experimental proof of this concept using a new system: a strained epitaxial quantum dot containing individual Fe(2+) ion. Magnetic character of the Fe(2+) ground state in a CdSe/ZnSe dot is revealed in photoluminescence experiments by exploiting a coupling between a confined exciton and the single-iron impurity. We also demonstrate that the Fe(2+) spin can be oriented by spin-polarized excitons, which opens a possibility of using it as an optically controllable two-level system free of nuclear spin fluctuations. PMID- 26818581 TI - Deterioration of teeth and alveolar bone loss due to chronic environmental high level fluoride and low calcium exposure. AB - OBJECTIVES: Health risks due to chronic exposure to highly fluoridated groundwater could be underestimated because fluoride might not only influence the teeth in an aesthetic manner but also seems to led to dentoalveolar structure changes. Therefore, we studied the tooth and alveolar bone structures of Dorper sheep chronically exposed to very highly fluoridated and low calcium groundwater in the Kalahari Desert in comparison to controls consuming groundwater with low fluoride and normal calcium levels within the World Health Organization (WHO) recommended range. MATERIALS AND METHODS: Two flocks of Dorper ewes in Namibia were studied. Chemical analyses of water, blood and urine were performed. Mineralized tissue investigations included radiography, HR-pQCT analyses, histomorphometry, energy-dispersive X-ray spectroscopy and X-ray diffraction analyses. RESULTS: Fluoride levels were significantly elevated in water, blood and urine samples in the Kalahari group compared to the low fluoride control samples. In addition to high fluoride, low calcium levels were detected in the Kalahari water. Tooth height and mandibular bone quality were significantly decreased in sheep, exposed to very high levels of fluoride and low levels of calcium in drinking water. Particularly, bone volume and cortical thickness of the mandibular bone were significantly reduced in these sheep. CONCLUSIONS: The current study suggests that chronic environmental fluoride exposure with levels above the recommended limits in combination with low calcium uptake can cause significant attrition of teeth and a significant impaired mandibular bone quality. CLINICAL RELEVANCE: In the presence of high fluoride and low calcium associated dental changes, deterioration of the mandibular bone and a potential alveolar bone loss needs to be considered regardless whether other signs of systemic skeletal fluorosis are observed or not. PMID- 26818583 TI - Effects of strain relaxation in Pr0.67Sr0.33MnO3 films probed by polarization dependent X-ray absorption near edge structure. AB - The Mn K edge X-ray absorption near edge structure (XANES) of Pr0.67Sr0.33MnO3 films with different thicknesses on (001) LaAlO3 substrate was measured, and the effects of strain relaxation on film properties were investigated. The films showed in-plane compressive and out-of-plane tensile strains. Strain relaxation occurred with increasing film thickness, affecting both lattice constant and MnO6 octahedral rotation. In polarization dependent XANES measurements using in-plane (parallel) and out-of-plane (perpendicular) geometries, the different values of absorption resonance energy Er confirmed the film anisotropy. The values of Er along these two directions shifted towards each other with increasing film thickness. Correlating with X-ray diffraction (XRD) results it is suggested that the strain relaxation decreased the local anisotropy and corresponding probability of electronic charge transfer between Mn 3d and O 2p orbitals along the in-plane and out-of-plane directions. The XANES results were used to explain the film-thickness dependent magnetic and transport properties. PMID- 26818582 TI - Influence of ultrasonic and sonic activation of epoxy-amine resin-based sealer on penetration of sealer into lateral canals. AB - OBJECTIVES: The aim of this study was to evaluate the efficacy of sonic and ultrasonic activation of epoxy-amine resin-based root canal sealer (2Seal; VDW GmbH, Munchen, Germany) on penetration of the sealer into lateral canals compared to non-activated filling. MATERIALS AND METHODS: Thirty-six single-rooted human anterior teeth were decoronated and prepared, using the ProTaper rotary system (Dentsply Maillefer, Ballaigues, Switzerland) to F4. After the completion of the clearing procedures, lateral canals were created at 2, 4, and 6 mm from the working length. The specimens were randomly divided into a control group (non activated sealer application) and two experimental groups that received a sealer application with either sonic or ultrasonic activation. The root canals were filled using cold lateral compaction and images were obtained from each lateral canals at 40* magnification using a stereomicroscope. The sealer penetration was evaluated using a four-grade scoring system. The data were evaluated statistically using the Kruskal-Wallis and Mann-Whitney U tests with a 95 % confidence level (P = 0.05). RESULTS: The ultrasonic activation resulted in a better sealer penetration compared with the non-activated and sonically activated groups (P < 0.001). Sonic activation also resulted in better sealer penetration compared to the non-activated group (P < 0.001). CONCLUSIONS: The use of the ultrasonic activation of an epoxy-amine resin-based sealer promoted greater sealer penetration into the lateral canals. Sonic activation was not effective as ultrasonic activation, but was more effective than the non-activated group. CLINICAL RELEVANCE: The ultrasonic activation of an epoxy-amine resin-based sealer could be beneficial in filling procedures. PMID- 26818584 TI - Xuefu Zhuyu decoction, a traditional Chinese medicine, provides neuroprotection in a rat model of traumatic brain injury via an anti-inflammatory pathway. AB - Neuroinflammation is central to the pathology of traumatic brain injury (TBI). Xuefu Zhuyu decoction (XFZY) is an effective traditional Chinese medicine to treat TBI. To elucidate its potential molecular mechanism, this study aimed to demonstrate that XFZY functions as an anti-inflammatory agent by inhibiting the PI3K-AKT-mTOR pathway. Sprague-Dawley rats were exposed to controlled cortical impact to produce a neuroinflammatory response. The treatment groups received XFZY (9 g/kg and 18 g/kg), Vehicle group and Sham group were gavaged with equal volumes of saline. The modified neurologic severity score (mNSS) and the Morris water maze test were used to assess neurological deficits. Arachidonic acid (AA) levels in brain tissue were measured using tandem gas chromatography-mass spectrometry. TNF-alpha and IL-1beta levels in injured ipsilateral brain tissue were detected by ELISA. AKT and mTOR expression were measured by western blot analysis. The results indicated that XFZY significantly enhanced spatial memory acquisition. XFZY (especially at a dose of 9 g/kg) markedly reduced the mNSS and levels of AA, TNF-alpha and IL-1beta. Significant downregulation of AKT/mTOR/p70S6K proteins in brain tissues was observed after the administration of XFZY (especially at a dose of 9 g/kg). XFZY may be a promising therapeutic strategy for reducing inflammation in TBI. PMID- 26818586 TI - Impact of resistance exercise on ribosome biogenesis is acutely regulated by post exercise recovery strategies. AB - Muscle hypertrophy occurs following increased protein synthesis, which requires activation of the ribosomal complex. Additionally, increased translational capacity via elevated ribosomal RNA (rRNA) synthesis has also been implicated in resistance training-induced skeletal muscle hypertrophy. The time course of ribosome biogenesis following resistance exercise (RE) and the impact exerted by differing recovery strategies remains unknown. In the present study, the activation of transcriptional regulators, the expression levels of pre-rRNA, and mature rRNA components were measured through 48 h after a single-bout RE. In addition, the effects of either low-intensity cycling (active recovery, ACT) or a cold-water immersion (CWI) recovery strategy were compared. Nine male subjects performed two bouts of high-load RE randomized to be followed by 10 min of either ACT or CWI. Muscle biopsies were collected before RE and at 2, 24, and 48 h after RE. RE increased the phosphorylation of the p38-MNK1-eIF4E axis, an effect only evident with ACT recovery. Downstream, cyclin D1 protein, total eIF4E, upstream binding factor 1 (UBF1), and c-Myc proteins were all increased only after RE with ACT. This corresponded with elevated abundance of the pre-rRNAs (45S, ITS-28S, ITS-5.8S, and ETS-18S) from 24 h after RE with ACT. In conclusion, coordinated upstream signaling and activation of transcriptional factors stimulated pre-rRNA expression after RE. CWI, as a recovery strategy, markedly blunted these events, suggesting that suppressed ribosome biogenesis may be one factor contributing to the impaired hypertrophic response observed when CWI is used regularly after exercise. PMID- 26818587 TI - Cost of Dementia and Its Correlation With Dependence. AB - OBJECTIVE: To estimate the cost of dementia care and its relation to dependence. METHOD: Disease severity and health care resource utilization was retrieved from the Swedish National Study on Aging and Care. Informal care was assessed with the Resource Utilization in Dementia instrument. A path model investigates the relationship between annual cost of care and dependence, cognitive ability, functioning, neuropsychiatric symptoms, and comorbidities. RESULTS: Average annual cost among patients diagnosed with dementia was ?43,259, primarily incurred by accommodation. Resource use, that is, institutional care, community care, and accommodation, and corresponding costs increased significantly by increasing dependency. Path analysis showed that cognitive ability, functioning, and neuropsychiatric symptoms were significantly correlated with dependence, which in turn had a strong impact on annual cost. DISCUSSION: This study confirms that cost of dementia care increases with dependence and that the impact of other disease indicators is mainly mediated by dependence. PMID- 26818585 TI - Skeletal muscle atrogene expression and insulin resistance in a rat model of polytrauma. AB - Polytrauma is a combination of injuries to more than one body part or organ system. Polytrauma is common in warfare, and in automobile and industrial accidents. The combination of injuries can include burn, fracture, hemorrhage, and trauma to the extremities or specific organ systems. Resistance to anabolic hormones, loss of muscle mass, and metabolic dysfunction can occur following injury. To investigate the effects of combined injuries, we have developed a highly reproducible rodent model of polytrauma. This model combines burn injury, soft tissue trauma, and penetrating injury to the gastrointestinal (GI) tract. Adult, male Sprague-Dawley rats were anesthetized with pentobarbital and subjected to a 15-20% total body surface area scald burn, or laparotomy and a single puncture of the cecum with a G30 needle, or the combination of both injuries (polytrauma). In the current studies, the inflammatory response to polytrauma was examined in skeletal muscle. Changes in skeletal muscle mRNA levels of the proinflammatory cytokines TNF-alpha, IL-1beta, and IL-6 were observed following single injuries and polytrauma. Increased expression of the E3 ubiquitin ligases Atrogin-1/FBX032 and TRIM63/MuRF-1 were measured following injury, as was skeletal muscle insulin resistance, as evidenced by decreased insulin-inducible insulin receptor (IR) and AKT/PKB (Protein Kinase B) phosphorylation. Changes in the abundance of IR and insulin receptor substrate-1 (IRS-1) were observed at the protein and mRNA levels. Additionally, increased TRIB3 mRNA levels were observed 24 h following polytrauma, the same time when insulin resistance was observed. This may suggest a role for TRIB3 in the development of acute insulin resistance following injury. PMID- 26818588 TI - Collagen barrier membranes adsorb growth factors liberated from autogenous bone chips. AB - OBJECTIVE: Collagen membranes serve as barriers to separate bone grafts from soft tissues. Bone grafts harvested with a bone scraper release growth factors activating transforming growth factor-beta (TGF-beta) signaling in mesenchymal cells. The aim of the present pilot study was to determine whether collagen membranes adsorb molecules from bone-conditioned medium (BCM) with the capacity to provoke the expression of TGF-beta target genes in vitro. MATERIALS AND METHODS: Collagen membranes were soaked in aqueous extracts from fresh and demineralized bone chips placed in cell culture medium. Recombinant human TGF beta1 served as control. Gingival fibroblasts were seeded onto the washed collagen membranes and evaluated for the expression of adrenomedullin, pentraxin 3, interleukin 11, and proteoglycan 4. Cell viability and morphology with phalloidin staining were also determined. RESULTS: Incubation of collagen membranes with BCM for at least one minute caused fibroblasts to decrease the expression of adrenomedullin and pentraxin 3, and to increase the expression of interleukin 11 and proteoglycan 4. Four different membrane treatments - incubated with recombinant TGF-beta1, pre-wetted with saline solution, exposed to UV light, and dry out and stored one week at room temperature - also provoked significant changes in gene expression. Likewise, conditioned medium from demineralized bone chips caused gene expression changes. BCM did not alter the viability or morphology of gingival fibroblasts. CONCLUSIONS: These findings demonstrate that collagen membranes rapidly adsorb the TGF-beta activity released from bone chips, a molecular process that might contribute to guided bone regeneration. PMID- 26818590 TI - Aminooxylation Horner-Wadsworth-Emmons Sequence for the Synthesis of Enantioenriched gamma-Functionalized Vinyl Sulfones. AB - An operationally simple protocol for the synthesis of gamma-hydroxy vinyl sulfones has been developed using a proline-based aldehyde aminooxylation, followed by a vinyl sulfone forming Horner-Wadsworth-Emmons olefination. The adducts, formed in high enantiopurity, were subsequently converted to gamma-azido vinyl sulfones, and azide-alkyne click chemistry enabled the synthesis of vinyl sulfone-based triazoles as potential nonpeptidic cysteine protease inhibitors. PMID- 26818591 TI - Genomic duplication problems for unrooted gene trees. AB - BACKGROUND: Discovering the location of gene duplications and multiple gene duplication episodes is a fundamental issue in evolutionary molecular biology. The problem introduced by Guigo et al. in 1996 is to map gene duplication events from a collection of rooted, binary gene family trees onto theirs corresponding rooted binary species tree in such a way that the total number of multiple gene duplication episodes is minimized. There are several models in the literature that specify how gene duplications from gene families can be interpreted as one duplication episode. However, in all duplication episode problems gene trees are rooted. This restriction limits the applicability, since unrooted gene family trees are frequently inferred by phylogenetic methods. RESULTS: In this article we show the first solution to the open problem of episode clustering where the input gene family trees are unrooted. In particular, by using theoretical properties of unrooted reconciliation, we show an efficient algorithm that reduces this problem into the episode clustering problems defined for rooted trees. We show theoretical properties of the reduction algorithm and evaluation of empirical datasets. CONCLUSIONS: We provided algorithms and tools that were successfully applied to several empirical datasets. In particular, our comparative study shows that we can improve known results on genomic duplication inference from real datasets. PMID- 26818589 TI - Myofibroblast secretome and its auto-/paracrine signaling. AB - Myofibroblasts (myoFb) are phenotypically transformed, contractile fibroblast like cells expressing alpha-smooth muscle actin microfilaments. They are integral to collagen fibrillogenesis with scar tissue formation at sites of repair irrespective of the etiologic origins of injury or tissue involved. MyoFb can persist long after healing is complete, where their ongoing turnover of collagen accounts for a progressive structural remodeling of an organ (a.k.a. fibrosis, sclerosis or cirrhosis). Such persistent metabolic activity is derived from a secretome consisting of requisite components in the de novo generation of angiotensin (Ang) II. Autocrine and paracrine signaling induced by tissue AngII is expressed via AT1 receptor ligand binding to respectively promote: i) regulation of myoFb collagen synthesis via the fibrogenic cytokine TGF-beta1-Smad pathway; and ii) dedifferentiation and protein degradation of atrophic myocytes immobilized and ensnared by fibrillar collagen at sites of scarring. Several cardioprotective strategies in the prevention of fibrosis and involving myofibroblasts are considered. They include: inducing myoFb apoptosis through inactivation of antiapoptotic proteins; AT1 receptor antagonist to interfere with auto-/paracrine myoFb signaling or to induce counterregulatory expression of ACE2; and attacking the AngII-AT1R-TGF-beta1-Smad pathway by antibody or the use of triplex-forming oligonucleotides. PMID- 26818592 TI - Cavitation of intercellular spaces is critical to establishment of hydraulic properties of compression wood of Chamaecyparis obtusa seedlings. AB - BACKGROUND AND AIMS: When the orientation of the stems of conifers departs from the vertical as a result of environmental influences, conifers form compression wood that results in restoration of verticality. It is well known that intercellular spaces are formed between tracheids in compression wood, but the function of these spaces remains to be clarified. In the present study, we evaluated the impact of these spaces in artificially induced compression wood in Chamaecyparis obtusa seedlings. METHODS: We monitored the presence or absence of liquid in the intercellular spaces of differentiating xylem by cryo-scanning electron microscopy. In addition, we analysed the relationship between intercellular spaces and the hydraulic properties of the compression wood. KEY RESULTS: Initially, we detected small intercellular spaces with liquid in regions in which the profiles of tracheids were not rounded in transverse surfaces, indicating that the intercellular spaces had originally contained no gases. In the regions where tracheids had formed secondary walls, we found that some intercellular spaces had lost their liquid. Cavitation of intercellular spaces would affect hydraulic conductivity as a consequence of the induction of cavitation in neighbouring tracheids. CONCLUSIONS: Our observations suggest that cavitation of intercellular spaces is the critical event that affects not only the functions of intercellular spaces but also the hydraulic properties of compression wood. PMID- 26818593 TI - Change in active transportation and weight gain in pregnancy. AB - BACKGROUND: Pregnancy is characterised by large weight gain over a short period, and often a notable change in mode of transportation. This makes pregnancy suitable for examining the plausible, but in the scientific literature still unclear, association between active transportation and weight gain. We hypothesize that women continuing an active mode of transportation to work or school from pre- to early pregnancy will have a lower gestational weight gain (GWG) than those who change to a less active mode of transportation. METHODS: We analysed prospective data from the Norwegian Fit for Delivery (NFFD) trial. Between September 2009 and February 2013 606 women were consecutively enrolled in median gestational week 16 (range; 8-20). Of 219 women who used an active mode of transportation (biking, walking, public transportation) pre-pregnancy, 66 (30%) converted to a less active mode in early pregnancy ("active-less active" group), and 153 (70%) continued with active transportation ("active-active" group). Pre pregnancy weight was self-reported. Weight at gestational (GA) weeks 16, 30, 36, and at term delivery was objectively measured. Weight gain was compared between the two groups. Linear mixed effects analysis of the repeated weight measures was performed including the group*time interaction. RESULTS: A significant overall group effect was observed for the four time points together ("active-active" group: 77.3 kg vs. "active-less active" group: 78.8 kg, p = 0.008). The interaction term group*time was significant indicating different weight gain throughout pregnancy for the two groups; the mean differences between the groups were 0.7 kg at week 16, 1.4 kg at week 30, 2.1 kg at week 36, and 2.2 kg at term delivery, respectively. CONCLUSION: The findings indicate that active transportation is one possible approach to prevent excessive weight gain in pregnancy. PMID- 26818595 TI - Insight into the adsorption profiles of the Saprolegnia monoica chitin synthase MIT domain on POPA and POPC membranes by molecular dynamics simulation studies. AB - The critical role of chitin synthases in oomycete hyphal tip growth has been established. A microtubule interacting and trafficking (MIT) domain was discovered in the chitin synthases of the oomycete model organism, Saprolegnia monoica. MIT domains have been identified in diverse proteins and may play a role in intracellular trafficking. The structure of the Saprolegnia monoica chitin synthase 1 (SmChs1) MIT domain has been recently determined by our group. However, although our in vitro assay identified increased strength in interactions between the MIT domain and phosphatidic acid (PA) relative to other phospholipids including phosphatidylcholine (PC), the mechanism used by the MIT domain remains unknown. In this work, the adsorption behavior of the SmChs1 MIT domain on POPA and POPC membranes was systematically investigated by molecular dynamics simulations. Our results indicate that the MIT domain can adsorb onto the tested membranes in varying orientations. Interestingly, due to the specific interactions between MIT residues and lipid molecules, the binding affinity to the POPA membrane is much higher than that to the POPC membrane. A binding hotspot, which is critical for the adsorption of the MIT domain onto the POPA membrane, was also identified. The lower binding affinity to the POPC membrane can be attributed to the self-saturated membrane surface, which is unfavorable for hydrogen-bond and electrostatic interactions. The present study provides insight into the adsorption profile of SmChs1 and additionally has the potential to improve our understanding of other proteins containing MIT domains. PMID- 26818596 TI - On Patient Safety: When Are We Too Old to Operate? PMID- 26818594 TI - Inference of domain-disease associations from domain-protein, protein-disease and disease-disease relationships. AB - BACKGROUND: Protein domains can be viewed as portable units of biological function that defines the functional properties of proteins. Therefore, if a protein is associated with a disease, protein domains might also be associated and define disease endophenotypes. However, knowledge about such domain-disease relationships is rarely available. Thus, identification of domains associated with human diseases would greatly improve our understanding of the mechanism of human complex diseases and further improve the prevention, diagnosis and treatment of these diseases. METHODS: Based on phenotypic similarities among diseases, we first group diseases into overlapping modules. We then develop a framework to infer associations between domains and diseases through known relationships between diseases and modules, domains and proteins, as well as proteins and disease modules. Different methods including Association, Maximum likelihood estimation (MLE), Domain-disease pair exclusion analysis (DPEA), Bayesian, and Parsimonious explanation (PE) approaches are developed to predict domain-disease associations. RESULTS: We demonstrate the effectiveness of all the five approaches via a series of validation experiments, and show the robustness of the MLE, Bayesian and PE approaches to the involved parameters. We also study the effects of disease modularization in inferring novel domain-disease associations. Through validation, the AUC (Area Under the operating characteristic Curve) scores for Bayesian, MLE, DPEA, PE, and Association approaches are 0.86, 0.84, 0.83, 0.83 and 0.79, respectively, indicating the usefulness of these approaches for predicting domain-disease relationships. Finally, we choose the Bayesian approach to infer domains associated with two common diseases, Crohn's disease and type 2 diabetes. CONCLUSIONS: The Bayesian approach has the best performance for the inference of domain-disease relationships. The predicted landscape between domains and diseases provides a more detailed view about the disease mechanisms. PMID- 26818597 TI - Editor's Spotlight/Take 5: Do Orthopaedic Surgeons Acknowledge Uncertainty? PMID- 26818598 TI - CORR Insights((r)): Is Vancomycin-only Prophylaxis for Patients With Penicillin Allergy Associated With Increased Risk of Infection After Arthroplasty? PMID- 26818599 TI - Effects of computer reminders on complications of peripheral venous catheters and nurses' adherence to a guideline in paediatric care--a cluster randomised study. AB - BACKGROUND: Reminder systems in electronic patient records (EPR) have proven to affect both health care professionals' behaviour and patient outcomes. The aim of this cluster randomised trial was to investigate the effects of implementing a clinical practice guideline (CPG) for peripheral venous catheters (PVCs) in paediatric care in the format of reminders integrated in the EPRs, on PVC-related complications, and on registered nurses' (RNs') self-reported adherence to the guideline. An additional aim was to study the relationship between contextual factors and the outcomes of the intervention. METHODS: The study involved 12 inpatient units at a paediatric university hospital. The reminders included choice of PVC, hygiene, maintenance, and daily inspection of PVC site. Primary outcome was documented signs and symptoms of PVC-related complications at removal, retrieved from the EPR. Secondary outcome was RNs' adherence to a PVC guideline, collected through a questionnaire that also included RNs' perceived work context, as measured by the Alberta Context Tool. Units were allocated into two strata, based on occurrence of PVCs. A blinded simple draw of lots from each stratum randomised six units to the control and intervention groups, respectively. Units were not blinded. The intervention group included 626 PVCs at baseline and 618 post-intervention and the control group 724 PVCs at baseline and 674 post-intervention. RNs included at baseline were 212 (65.4 %) and 208 (71.5 %) post-intervention. RESULTS: No significant effect was found for the computer reminders on PVC-related complications nor on RNs' adherence to the guideline recommendations. The complication rate at baseline and post-intervention was 40.6 % (95 % confidence interval (CI) 36.7-44.5) and 41.9 % (95 % CI 38.0-45.8), for the intervention group and 40.3 % (95 % CI 36.8-44.0) and 46.9 % (95 % CI 43.1 50.7) for the control. In general, RNs' self-rated work context varied from moderately low to moderately high, indicating that conditions for a successful implementation to occur were less optimal. CONCLUSIONS: The reminders might have benefitted from being accompanied by a tailored intervention that targeted specific barriers, such as the low frequency of recorded reasons for removal, the low adherence to daily inspection of PVC sites, and the lack of regular feedback to the RNs. TRIAL REGISTRATION: Current Controlled Trials ISRCTN44819426. PMID- 26818601 TI - Double robust estimator of average causal treatment effect for censored medical cost data. AB - In observational studies, estimation of average causal treatment effect on a patient's response should adjust for confounders that are associated with both treatment exposure and response. In addition, the response, such as medical cost, may have incomplete follow-up. In this article, a double robust estimator is proposed for average causal treatment effect for right censored medical cost data. The estimator is double robust in the sense that it remains consistent when either the model for the treatment assignment or the regression model for the response is correctly specified. Double robust estimators increase the likelihood the results will represent a valid inference. Asymptotic normality is obtained for the proposed estimator, and an estimator for the asymptotic variance is also derived. Simulation studies show good finite sample performance of the proposed estimator and a real data analysis using the proposed method is provided as illustration. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26818600 TI - Efficacy of Human Adipose Tissue-Derived Stem Cells on Neonatal Bilirubin Encephalopathy in Rats. AB - Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in 7-day-old rats to induce haemolysis and then infused sulfisoxazole into the same rats at day 9 to block bilirubin binding sites in the albumin. We have investigated the effectiveness of human adiposity-derived stem cells as a therapeutic paradigm for perinatal neuronal repair in a kernicterus animal model. The level of total bilirubin, indirect bilirubin, brain bilirubin and brain iron was significantly increased in the modelling group. There was a significant decreased in all severity levels of the auditory brainstem response test in the two modelling group. Akinesia, bradykinesia and slip were significantly declined in the experience group. Apoptosis in basal ganglia and cerebellum were significantly decreased in the stem cell-treated group in comparison to the vehicle group. All severity levels of the auditory brainstem response tests were significantly decreased in 2-month-old rats. Transplantation results in the substantial alleviation of walking impairment, apoptosis and auditory dysfunction. This study provides important information for the development of therapeutic strategies using human adiposity-derived stem cells in prenatal brain damage to reduce potential sensori motor deficit. PMID- 26818602 TI - Therapeutic potential of Takeda-G-protein-receptor-5 (TGR5) agonists. Hope or hype? AB - The gastrointestinal tract regulates glucose and energy metabolism, and there is increasing recognition that bile acids function as key signalling molecules in these processes. For example, bile acid changes that occur after bariatric surgery have been implicated in the effects on satiety, lipid and cholesterol regulation, glucose and energy metabolism, and the gut microbiome. In recent years, Takeda-G-protein-receptor-5 (TGR5), a bile acid receptor found in widely dispersed tissues, has been the target of significant drug discovery efforts in the hope of identifying effective treatments for metabolic diseases including type 2 diabetes, obesity, atherosclerosis, fatty liver disease and cancer. Although the benefits of targeting the TGR5 receptor are potentially great, drug development work to date has identified risks that include histopathological changes, tumorigenesis, gender differences, and questions about the translation of animal data to humans. The present article reviews the noteworthy challenges that must be addressed along the path of development of a safe and effective TGR5 agonist therapy. PMID- 26818603 TI - Self-Styled ZnO Nanostructures Promotes the Cancer Cell Damage and Supresses the Epithelial Phenotype of Glioblastoma. AB - Extensive researches have been done on the applications of zinc oxide nanoparticles (ZnO-NPs) for the biological purposes. However, the role and toxicity mechanisms of ZnO nanostructures (ZnO-NSts) such as nanoplates (NPls), nanorods (NRs), nanosheets (NSs), nanoflowers (NFs) on cancer cells are not largely known. Present study was focused to investigate the possible mechanisms of apoptosis induced by self-designed ZnO-NSts, prepared at fix pH via solution process and exposed against human T98G gliomas including various cancers and non malignant embryonic kidney HEK293, MRC5 fibroblast cells. NSts were used for the induction of cell death in malignant human T98G gliomas including various cancers and compared with the non-malignant cells. Notably, NRs were found to induce higher cytotoxicity, inhibitory effects on cancer and normal cells in a dose dependent manner. We also showed that NRs induced cancer cell death through oxidative stress and caspase-dependent pathways. Furthermore, quantitative and qualitative analysis of ZnO-NSts have also been confirmed by statistical analytical parameters such as precision, accuracy, linearity, limits of detection and limit of quantitation. These self-styled NSts could provide new perception in the research of targeted cancer nanotechnology and have potentiality to improve new therapeutic outcomes with poor diagnosis. PMID- 26818604 TI - Post-prandial glucose and insulin responses of hummus alone or combined with a carbohydrate food: a dose-response study. AB - OBJECTIVES: Pulses are low glycemic index (GI) foods and have been associated with reduced risk of heart disease, diabetes and some cancers. However the blood glucose and insulin responses of hummus, a food containing chickpea, have not been thoroughly tested. METHODS: Ten healthy subjects each consumed 11 breakfast study meals in randomized order over a period of 15 weeks. Hummus was consumed alone at three doses (2.7 g, 10.8 g and 25 g available carbohydrate [avCHO] portions) and with 50 g avCHO from white bread at three doses (2.7 g, 5.4 g and 10.8 g avCHO portions). The responses elicited by hummus alone were compared with 25 g avCHO portions of white bread, while those after hummus plus white bread were compared with 50 g avCHO from white bread. Plasma glucose and serum insulin responses were monitored over two hours and the GI and insulin index (II) calculated using standard methodology. RESULTS: The GI and II of hummus were 15 +/- 3 and 52 +/- 13, respectively, and were significantly lower than white bread (P < 0.05). The glucose and insulin incremental area under the curve (IAUC) for hummus alone were significantly lower than white bread except for insulin IAUC of hummus 25 g avCHO. The peak rise of blood glucose and insulin after hummus were significantly lower than after white bread. Glucose and insulin IAUC after adding hummus to bread did not differ significantly from white bread alone. However the blood glucose 45 min after adding 25 g avCHO from hummus to white bread was significantly lower while at 120 min it was significantly higher than after white bread alone. CONCLUSIONS: This study demonstrated that, similar to chickpeas, hummus has a very low GI and II. Postprandial glucose responses were 4 times less than that of white bread and did not compromise insulin levels. PMID- 26818605 TI - Distinct intracellular signaling mediates C-MET regulation of dendritic growth and synaptogenesis. AB - Hepatocyte growth factor (HGF) activation of the MET receptor tyrosine kinase influences multiple neurodevelopmental processes. Evidence from human imaging and mouse models shows that, in the forebrain, disruptions in MET signaling alter circuit formation and function. One likely means of modulation is by controlling neuron maturation. Here, we examined the signaling mechanisms through which MET exerts developmental effects in the neocortex. In situ hybridization revealed that hgf is located near MET-expressing neurons, including deep neocortical layers and periventricular zones. Western blot analyses of neocortical crude membranes demonstrated that HGF-induced MET autophosphorylation peaks during synaptogenesis, with a striking reduction in activation between P14 and P17 just before pruning. In vitro analysis of postnatal neocortical neurons assessed the roles of intracellular signaling following MET activation. There is rapid, HGF induced phosphorylation of MET, ERK1/2, and Akt that is accompanied by two major morphological changes: increases in total dendritic growth and synapse density. Selective inhibition of each signaling pathway altered only one of the two distinct events. MAPK/ERK pathway inhibition significantly reduced the HGF induced increase in dendritic length, but had no effect on synapse density. In contrast, inhibition of the PI3K/Akt pathway reduced HGF-induced increases in synapse density, with no effect on dendritic length. The data reveal a key role for MET activation during the period of neocortical neuron growth and synaptogenesis, with distinct biological outcomes mediated via discrete MET linked intracellular signaling pathways in the same neurons. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1160-1181, 2016. PMID- 26818607 TI - High frequency of OTOF mutations in Chinese infants with congenital auditory neuropathy spectrum disorder. AB - Auditory neuropathy spectrum disorder (ANSD) is one of the most common diseases leading to hearing and speech communication barriers in infants and young children. The OTOF gene is the first gene identified for autosomal recessive non syndromic ANSD, and patients with OTOF mutations have shown marked improvement of auditory functions from the cochlear implantation, but the true involvement of OTOF mutations in Chinese ANSD patients is still unknown which precludes the effective management of this disease. Here, we investigated the contribution of OTOF mutations to congenital ANSD patients in China. In all, 37 infants and young Children with ANSD were screened for all the exons of OTOF gene, of them 34 patients had no neonatal risk factors who were considered as congenital ANSD. The clinical manifestation and audiometric features were also investigated and compared in patients with and without OTOF mutations. In all, 14 of these subjects were shown to carry two or three mutant alleles of OTOF with the high frequency of 41.2% in congenital ANSD patients. In total, 15 novel pathogenic mutations and 10 reported mutations were identified. Our results confirmed that mutations in OTOF gene were a major cause of congenital ANSD in China. Identification of OTOF mutations can facilitate diagnosis, clinical intervention and counseling for congenital ANSD. PMID- 26818606 TI - Mesenchymal stem cells for treating ocular surface diseases. AB - Mesenchymal stem cells (MSC) have become a promising tool for cell therapy in regenerative medicine. They are readily available, demonstrate powerful differentiation capabilities and present immunosuppressive properties that aid them in surviving from host immune rejection for its great potential use in allograft. Currently clinical trials are underway using MSC, both culture expanded allogeneic and autologous, for the treatment of a range of diseases not treatable by conventional therapies. A vast array of studies has dedicated towards the use of MSC for treating corneal diseases with very promising outcomes. MSC have successfully differentiated into keratocytes both in vitro and in vivo, and corneal epithelial cells in vitro, but it is uncertain if MSC can assume corneal epithelial cells in vivo. However, to date few studies have unequivocally established the efficacy of MSC for treating corneal endothelial defects. Currently, the diversity in protocols of the isolation and expansion of MSC are hindering to the assessment of cell treatment ability and the further development of treatment regimens. Therefore, future studies should develop international standards for MSC isolation and characterization. In this review, we discuss recent advances in MSC for treating ocular surface diseases. PMID- 26818608 TI - Modeling organic matter and nitrogen removal from domestic wastewater in a pilot scale vertical subsurface flow constructed wetland. AB - Constructed wetlands have become an attractive alternative for wastewater treatment. However, there is not a globally accepted mathematical model to predict their performance. In this study, the VS2DTI software was used to predict the effluent biochemical oxygen demand (BOD) and total nitrogen (TN) in a pilot scale vertical flow constructed wetland (VFCW) treating domestic wastewater. After a 5-week adaptation period, the pilot system was monitored for another 6 weeks. Experiments were conducted at hydraulic retention times (HRTs) in the range of 2-4 days with Typha latifolia as the vegetation. The raw wastewater concentrations ranged between 144-430 and 122-283 mg L(-1) for BOD5 and TN, respectively. A first-order kinetic model coupled with the advection/dispersion and Richards' equations was proposed to predict the removal rates of BOD5 and TN from domestic wastewater. Two main physical processes were modeled in this study, porous material water flow and solute transport through the different layers of the VFCW to simulate the constructed wetland (CW) conditions. The model was calibrated based on the BOD5 and TN degradation constants. The model indicated that most of BOD and TN (88 and 92%, respectively) were removed through biological activity followed by adsorption. It was also observed that the evapotranspiration was seen to have a smaller impact. An additional data series of effluent BOD and TN was used for model validation. The residual analysis of the calibrated model showed a relatively random pattern, indicating a decent fit. Thus, the VS2DTI was found to be a useful tool for CW simulation. PMID- 26818609 TI - Limitations of body mass index to assess body composition due to sarcopenic obesity during leukemia therapy. AB - Obesity as defined by body mass index percentile (BMI%) is strongly associated with relapse and poorer survival in childhood ALL. Whether BMI% accurately reflects body fat percentage (BF%) in this population is unknown. We conducted a prospective study assessing body composition during frontline ALL therapy. Dual energy X-ray absorptiometry measured BF% and lean muscle mass (LMM) at diagnosis, end of Induction, and end of Delayed Intensification. Sarcopenic obesity (gain in BF% with loss of LMM) was surprisingly common during ALL treatment, resulting in poor correlation between changes in BMI% (expressed as Z-score) and BF% overall (r = -0.05) and within patients (r = -0.09). BMI Z-score and BF% changed in opposite directions in >50% of interval assessments. While BMI% at diagnosis is a suitable predictor of obesity/BF% for epidemiological studies, change in BMI% (as expressed as Z-score) does not reflect body composition. Studies evaluating obesity in leukemia should consider using direct measures of body composition. PMID- 26818610 TI - Focal exposure of limited lung volumes to high-dose irradiation down-regulated organ development-related functions and up-regulated the immune response in mouse pulmonary tissues. AB - BACKGROUND: Despite the emergence of stereotactic body radiotherapy (SBRT) for treatment of medically inoperable early-stage non-small-cell lung cancer patients, the molecular effects of focal exposure of limited lung volumes to high dose radiation have not been fully characterized. This study was designed to identify molecular changes induced by focal high-dose irradiation using a mouse model of SBRT. RESULTS: Central areas of the mouse left lung were focally irradiated (3 mm in diameter) with a single high-dose of radiation (90 Gy). Temporal changes in gene expression in the irradiated and non-irradiated neighboring lung regions were analyzed by microarray. For comparison, the long term effect (12 months) of 20 Gy radiation on a diffuse region of lung was also measured. The majority of genes were down-regulated in the focally-irradiated lung areas at 2 to 3 weeks after irradiation. This pattern of gene expression was clearly different than gene expression in the diffuse region of lungs exposed to low-dose radiation. Ontological and pathway analyses indicated these down regulated genes were mainly associated with organ development. Although the number was small, genes that were up-regulated after focal irradiation were associated with immune-related functions. The temporal patterns of gene expression and the associated biological functions were also similar in non irradiated neighboring lung regions, although statistical significance was greatly reduced when compared with those from focally-irradiated areas of the lung. From network analysis of temporally regulated genes, we identified inter related modules associated with diverse functions, including organ development and the immune response, in both the focally-irradiated regions and non irradiated neighboring lung regions. CONCLUSIONS: Focal exposure of lung tissue to high-dose radiation induced expression of genes associated with organ development and the immune response. This pattern of gene expression was also observed in non-irradiated neighboring areas of lung tissue, indicating a global lung response to focal high-dose irradiation. PMID- 26818611 TI - Trust in telemedicine portals for rehabilitation care: an exploratory focus group study with patients and healthcare professionals. AB - BACKGROUND: For many eServices, end-user trust is a crucial prerequisite for use. Within the context of Telemedicine, the role of trust has hardly ever been studied. In this study, we explored what determines trust in portals that facilitate rehabilitation therapy, both from the perspective of the patient and the healthcare professional. METHODS: We held two focus groups with patients (total n = 15) and two with healthcare professionals (total n = 13) in which we discussed when trust matters, what makes up trust in a rehabilitation portal, what effect specific design cues have, and how much the participants trust the use of activity sensor data for informing treatment. RESULTS: Trust in a rehabilitation portal is the sum of trust in different factors. These factors and what makes up these factors differ for patients and healthcare professionals. For example, trust in technology is made up, for patients, mostly by a perceived level of control and privacy, while for healthcare professionals, a larger and different set of issues play a role, including technical reliability and a transparent data storage policy. Healthcare professionals distrust activity sensor data for informing patient treatment, as they think that sensors are unable to record the whole range of movements that patients make (e.g., walking and ironing clothes). CONCLUSIONS: The set of factors that affect trust in a rehabilitation portal are different from the sets that have been found for other contexts, like eCommerce. Trust in telemedicine technology should be studied as a separate subject to inform the design of reliable interventions. PMID- 26818613 TI - A Novel Prevention Bundle to Reduce Surgical Site Infections in Pediatric Spinal Fusion Patients. AB - BACKGROUND: The Surgical Care Improvement Project bundle emphasizes operative infection prevention practices. Despite implementing the Surgical Care Improvement Project bundle in 2008, spinal fusion surgical site infections (SF SSI) continued to be prevalent for this low-volume, high-risk surgery. OBJECTIVE: To design a combined pre-, peri-, and postoperative bundle (PPPB) that would lead to sustained reductions in SF-SSI rates. DESIGN: Quality improvement project, before-after trial with cost-effectiveness analysis. SETTING: Children's hospital. PATIENTS: All spinal fusion patients, 2008-2015. INTERVENTION: A multidisciplinary team developed the PPPB composed of Surgical Care Improvement Project elements plus improved wound care practices, nursing standard of care, dedicated nursing unit, dermatology assessment tool and consultation, nursing education tool using "teach back" technique, and a "Back Home" kit. SF-SSI rates were compared before (2008-2010) and after (2011-February 2015) implementation of PPPB. PPPB compliance was monitored. RESULTS: A total of 224 SF surgeries were performed from 2008 to February 2015. Pre-PPPB analysis revealed median time to SF-SSI of 28 days, secondary to skin and bowel flora. Mean 3-year pre-PPPB SF-SSI rate per 100 SF surgeries was 8.2 (8/98) (2008: 13.3 [4/30], 2009: 2.7 [1/37], 2010: 9.7 [3/31]). Mean SF-SSI rate after PPPB was 2.4 (3/126) (January 2011 February 2015); there was a 71% reduction in mean SSI rate (P=.0695). No SF-SSI occurred in neuromuscular patients (P=.008) after PPPB. Compliance with PPPB elements has been 100%. CONCLUSIONS: PPPB led to sustained improvement in SF-SSI rates over 50 months. The PPPB could be reproduced for other surgeries. PMID- 26818612 TI - The effect of the rotator interval on glenohumeral kinematics during abduction. AB - BACKGROUND: The rotator interval (RI) has been exploited as a potentially benign point of entry into the glenohumeral (GH) joint. Bounded by the supraspinatus, subscapularis and coracoid process of the scapula, the RI is believed to be important in the shoulder's soft tissue balancing and function. However, the role of the RI in shoulder kinematics is not fully understood. The purpose of this study is to describe the effect of the RI on GH motion during abduction of the arm. METHODS: Six shoulders from three cadaveric torsos were studied to assess the impact of changes in the RI during abduction under four conditions: Intact (Baseline), Opened, Repaired (repaired with side-to-side tissue approximation, no overlap) and Tightened (repaired with 1 cm overlap). For each group, the GH translation and area under the Curve (AUC) were measured during abduction using an intact cadaveric shoulder (intact torso). RESULTS: GH kinematics varied in response to each intervention and throughout the entire abduction arc. Opening the RI caused a significant change in GH translation. The Repair and Tightened groups behaved similarly along all axes of GH motion. CONCLUSIONS: The RI is central to normal GH kinematics. Any insult to the tissue's integrity alters the shoulder's motion throughout abduction. In this model, closing the RI side-to side has the same effect as tightening the RI. Since suture closure may offer the same benefit as tightening the RI, clinicians should consider this effect when treating patients with shoulder laxity. This investigation provides an improved perspective on the role of the RI on GH kinematics during abduction. When managing shoulder pathology, surgeons should consider how these different methods of RI closure affect the joint's motion. In different circumstances, the surgical approach to the RI can be tailored to address each patient's specific needs. PMID- 26818614 TI - What happens when one leaves soft contact lenses in for three weeks? A case of bilateral, severe pseudomonas keratitis from contact lenses purchased over the internet. PMID- 26818615 TI - Developments in contact lens measurement: A comparative study of industry standard geometric inspection and optical coherence tomography. AB - PURPOSE: The aim of this study was to compare a developmental optical coherence tomography (OCT) based contact lens inspection instrument to a widely used geometric inspection instrument (Optimec JCF), to establish the capability of a market focused OCT system. METHODS: Measurements of 27 soft spherical contact lenses were made using the Optimec JCF and a new OCT based instrument, the Optimec is830. Twelve of the lenses analysed were specially commissioned from a traditional hydrogel (Contamac GM Advance 49%) and 12 from a silicone hydrogel (Contamac Definitive 65), each set with a range of back optic zone radius (BOZR) and centre thickness (CT) values. Three commercial lenses were also measured; CooperVision MyDay (Stenfilcon A) in -10D, -3D and +6D powers. Two measurements of BOZR, CT and total diameter were made for each lens in temperature controlled saline on both instruments. RESULTS: The results showed that the is830 and JCF measurements were comparable, but that the is830 had a better repeatability coefficient for BOZR (0.065mm compared to 0.151mm) and CT (0.008mm compared to 0.027mm). Both instruments had similar results for total diameter (0.041mm compared to 0.044mm). CONCLUSIONS: The OCT based instrument assessed in this study is able to match and improve on the JCF instrument for the measurement of total diameter, back optic zone radius and centre thickness for soft contact lenses in temperature controlled saline. PMID- 26818616 TI - The global prevalence of IBS in adults remains elusive due to the heterogeneity of studies: a Rome Foundation working team literature review. AB - OBJECTIVES: The global prevalence of IBS is difficult to ascertain, particularly in light of the heterogeneity of published epidemiological studies. The aim was to conduct a literature review, by experts from around the world, of community based studies on IBS prevalence. DESIGN: Searches were conducted using predetermined search terms and eligibility criteria, including papers in all languages. Pooled prevalence rates were calculated by combining separate population survey prevalence estimates to generate an overall combined meta prevalence estimate. The heterogeneity of studies was assessed. RESULTS: 1451 papers were returned and 83, including 288 103 participants in 41 countries, met inclusion criteria. The mean prevalence among individual countries ranged from 1.1% in France and Iran to 35.5% in Mexico. There was significant variance in pooled regional prevalence rates ranging from 17.5% (95% CI 16.9% to 18.2%) in Latin America, 9.6% (9.5% to 9.8%) in Asia, 7.1% (8.0% to 8.3%) in North America/Europe/Australia/New Zealand, to 5.8% (5.6% to 6.0%) in the Middle East and Africa. There was a significant degree of heterogeneity with the percentage of residual variation due to heterogeneity at 99.9%. CONCLUSIONS: The main finding is the extent of methodological variance in the studies reviewed and the degree of heterogeneity among them. Based on this, we concluded that publication of a single pooled global prevalence rate, which is easily calculated, would not be appropriate or contributory. Furthermore, we believe that future studies should focus on regional and cross-cultural differences that are more likely to shed light on pathophysiology. PMID- 26818618 TI - Effects of enteral polymeric diet on gut microbiota in children with Crohn's disease. PMID- 26818617 TI - Signalling via the osteopontin and high mobility group box-1 axis drives the fibrogenic response to liver injury. AB - OBJECTIVE: Liver fibrosis is associated with significant collagen-I deposition largely produced by activated hepatic stellate cells (HSCs); yet, the link between hepatocyte damage and the HSC profibrogenic response remains unclear. Here we show significant induction of osteopontin (OPN) and high-mobility group box-1 (HMGB1) in liver fibrosis. Since OPN was identified as upstream of HMGB1, we hypothesised that OPN could participate in the pathogenesis of liver fibrosis by increasing HMGB1 to upregulate collagen-I expression. DESIGN AND RESULTS: Patients with long-term hepatitis C virus (HCV) progressing in disease stage displayed enhanced hepatic OPN and HMGB1 immunostaining, which correlated with fibrosis stage, whereas it remained similar in non-progressors. Hepatocyte cytoplasmic OPN and HMGB1 expression was significant while loss of nuclear HMGB1 occurred in patients with HCV-induced fibrosis compared with healthy explants. Well-established liver fibrosis along with marked induction of HMGB1 occurred in CCl4-injected OpnHep transgenic yet it was less in wild type and almost absent in Opn-/- mice. Hmgb1 ablation in hepatocytes (Hmgb1DeltaHep) protected mice from CCl4-induced liver fibrosis. Coculture with hepatocytes that secrete OPN plus HMGB1 and challenge with recombinant OPN (rOPN) or HMGB1 (rHMGB1) enhanced collagen-I expression in HSCs, which was blunted by neutralising antibodies (Abs) and by Opn or Hmgb1 ablation. rOPN induced acetylation of HMGB1 in HSCs due to increased NADPH oxidase activity and the associated decrease in histone deacetylases 1/2 leading to upregulation of collagen-I. Last, rHMGB1 signalled via receptor for advanced glycation end-products and activated the PI3K-pAkt1/2/3 pathway to upregulate collagen-I. CONCLUSIONS: During liver fibrosis, the increase in OPN induces HMGB1, which acts as a downstream alarmin driving collagen-I synthesis in HSCs. PMID- 26818619 TI - Global patterns and trends in colorectal cancer incidence and mortality. AB - OBJECTIVE: The global burden of colorectal cancer (CRC) is expected to increase by 60% to more than 2.2 million new cases and 1.1 million deaths by 2030. In this study, we aim to describe the recent CRC incidence and mortality patterns and trends linking the findings to the prospects of reducing the burden through cancer prevention and care. DESIGN: Estimates of sex-specific CRC incidence and mortality rates in 2012 were extracted from the GLOBOCAN database. Temporal patterns were assessed for 37 countries using data from Cancer Incidence in Five Continents (CI5) volumes I-X and the WHO mortality database. Trends were assessed via the annual percentage change using joinpoint regression and discussed in relation to human development levels. RESULTS: CRC incidence and mortality rates vary up to 10-fold worldwide, with distinct gradients across human development levels, pointing towards widening disparities and an increasing burden in countries in transition. Generally, CRC incidence and mortality rates are still rising rapidly in many low-income and middle-income countries; stabilising or decreasing trends tend to be seen in highly developed countries where rates remain among the highest in the world. CONCLUSIONS: Patterns and trends in CRC incidence and mortality correlate with present human development levels and their incremental changes might reflect the adoption of more western lifestyles. Targeted resource-dependent interventions, including primary prevention in low income, supplemented with early detection in high-income settings, are needed to reduce the number of patients with CRC in future decades. PMID- 26818621 TI - Editorial: Why still study bacterial toxins in the third millennium? PMID- 26818622 TI - The Emerging Zika Pandemic: Enhancing Preparedness. PMID- 26818620 TI - Nucleosome architecture throughout the cell cycle. AB - Nucleosomes provide additional regulatory mechanisms to transcription and DNA replication by mediating the access of proteins to DNA. During the cell cycle chromatin undergoes several conformational changes, however the functional significance of these changes to cellular processes are largely unexplored. Here, we present the first comprehensive genome-wide study of nucleosome plasticity at single base-pair resolution along the cell cycle in Saccharomyces cerevisiae. We determined nucleosome organization with a specific focus on two regulatory regions: transcription start sites (TSSs) and replication origins (ORIs). During the cell cycle, nucleosomes around TSSs display rearrangements in a cyclic manner. In contrast to gap (G1 and G2) phases, nucleosomes have a fuzzier organization during S and M phases, Moreover, the choreography of nucleosome rearrangements correlate with changes in gene expression during the cell cycle, indicating a strong association between nucleosomes and cell cycle-dependent gene functionality. On the other hand, nucleosomes are more dynamic around ORIs along the cell cycle, albeit with tighter regulation in early firing origins, implying the functional role of nucleosomes on replication origins. Our study provides a dynamic picture of nucleosome organization throughout the cell cycle and highlights the subsequent impact on transcription and replication activity. PMID- 26818623 TI - Failure rate and complications associated with the use of spinal catheters for the management of inadvertent dural puncture in the parturient: a retrospective comparison with re-sited epidural catheters. AB - Objective To report on the failure rate of spinal catheters placed following inadvertent dural puncture (IDP) compared with re-sited epidural catheters in the obstetric population. Research design and methods Patients who experienced IDP during epidural or combined spinal epidural placement with 17 or 18 gauge Tuohy needles for labor analgesia between 2003 and 2014 were identified using our post dural puncture headache (PDPH) database. Patients were categorized into two groups: those who had spinal catheters inserted and those who had epidural catheters re-sited. Main outcome measure Failure rate associated with spinal or re-sited epidural catheters (defined as need for repeat block or alternative analgesic modality). Secondary outcomes were incidence of PDPH, need for epidural blood patch (EBP), and adverse events. Results A total of 109 patients were included in the final analysis; 79 ultimately had spinal catheters and 30 ultimately had re-sited epidural catheters. There were no differences between spinal catheters and re-sited epidural catheters in failure rate (22% vs. 13%, P = 0.33), incidence of PDPH (73% vs. 60%, P = 0.24), need for EBP (42% vs. 30%, P = 0.28), number of headache days, or maximum headache scores. There was also no difference in the rate of adverse events including high block levels, hypotension, and fetal bradycardia (9% vs. 7%, P = 1.0) between the two groups. Conclusions There were no differences in failure rates, PDPH outcomes, or adverse events between spinal catheters and re-sited epidural catheters following IDP in parturients receiving labor analgesia. Limitations of the study include its single-center retrospective non-randomized design, and the uneven number of patients in the two groups with a relatively small number in the re-sited epidural catheter group. PMID- 26818624 TI - Saliva and Plasma Monohydroxycarbamazepine Concentrations in Pediatric Patients With Epilepsy. AB - BACKGROUND: Monohydroxycarbamazepine (MHD, 10-hydroxy-carbamazepine) is the main active metabolite of oxcarbazepine (OXC). The present study aims to investigate the relationship between plasma and saliva concentrations of MHD in Chinese children with epilepsy. METHODS: Plasma and saliva samples were collected and MHD levels were measured by high-performance liquid chromatography system. Linear regression analysis was conducted between the dose of OXC and saliva concentrations, between the dose of OXC and plasma concentrations, and between the saliva concentrations and plasma concentrations. Student's t-test was used for unpaired data. A one-way analysis of variance was used for analyzing co medication in subgroups of patients. RESULTS: A total of 58 blood samples and 58 saliva samples were obtained from 52 pediatric epileptic patients, with a median age of 5.67 years (0.58-15 years, 23 males and 29 females). There was an apparent positive correlation between the plasma and saliva MHD concentrations [Y = 0.77x 0.85 (n = 58), R = 0.908, P < 0.01]. MHD plasma and saliva concentrations were positively correlated to daily drug dose (r = 0.461 and 0.417; P < 0.01 respectively). The saliva/plasma MHD ratio was around 0.71 and had no significant difference with age, gender, and combined medications. When data were analyzed for subgroups (one group taking OXC as monotherapy, the second group taking OXC in add-on with non-enzyme-inducing antiepileptic drugs, and the third group taking OXC in add-on with hepatic-enzyme-inducing antiepileptic drugs or moderate inducers), no significant difference was found between plasma and saliva MHD concentrations in all the above 3 groups. CONCLUSIONS: High correlation between plasma and saliva MHD levels supported the use of saliva as an alternative to plasma for OXC monitoring in children with epilepsy. PMID- 26818625 TI - S-Warfarin Limited Sampling Models to Estimate Area Under the Concentration Versus Time Curve for Cytochrome P450 2C9 Baseline Activity and After Induction. AB - BACKGROUND: Phenotyping cytochrome P450 (CYP) 2C9 activity using S-warfarin has routinely required extensive blood sampling over at least 96 hours after dose to estimate the area under the concentration time curve from zero to infinity (AUC). Alternatively, S-warfarin limited sampling models (LSMs) using one or 2 concentration timepoints have been proposed to estimate AUC. This study evaluated whether S-warfarin LSMs accurately estimate CYP2C9 baseline and induction conditions in healthy adults and in advanced-stage cancer patients. METHODS: Plasma S-warfarin concentrations from healthy adults (n = 92) and in advanced stage cancer patients (n = 22) were obtained from 6 published studies where a single 10 mg dose of oral warfarin was administered at CYP2C9 baseline and induction conditions. S-warfarin observed AUC was determined by noncompartmental analysis, whereas estimated AUC was calculated from the LSMs. Bias and precision were assessed by percent mean prediction error, percent mean absolute error, and percent root mean square error. RESULTS: Different results were observed for S warfarin LSMs in estimating CYP2C9 baseline activity, with most studies resulting in unacceptable bias and precision. The percent mean prediction error, percent mean absolute error, and/or percent root mean square error exceeded acceptable limits for LSMs in patients with advanced-stage cancer and during CYP2C9 induction with lopinavir/ritonavir. CONCLUSIONS: The differing results during CYP2C9 baseline conditions, as well as unacceptable bias and precision in patients with advanced cancer and during CYP2C9 induction, considerably limit the widespread use of previously published S-warfarin LSMs. PMID- 26818626 TI - BsRADseq: screening DNA methylation in natural populations of non-model species. AB - Epigenetic modifications are expected to occur at a much faster rate than genetic mutations, potentially causing isolated populations to stochastically drift apart, or if they are subjected to different selective regimes, to directionally diverge. A high level of genome-wide epigenetic divergence between individuals occupying distinct habitats is therefore predicted. Here, we introduce bisulfite converted restriction site associated DNA sequencing (bsRADseq), an approach to quantify the level of DNA methylation differentiation across multiple individuals. This reduced representation method is flexible in the extent of DNA sequence interrogated. We showcase its applicability in three natural systems, each comprising individuals adapted to divergent environments: a diploid plant (Heliosperma, Caryophyllaceae), a tetraploid plant (Dactylorhiza, Orchidaceae) and an animal (Gasterosteusaculeatus, Gasterosteidae). We present a robust bioinformatic pipeline, combining tools for RAD locus assembly, SNP calling, bisulfite-converted read mapping and DNA methylation calling to analyse bsRADseq data with or without a reference genome. Importantly, our approach accurately distinguishes between SNPs and methylation polymorphism (SMPs). Although DNA methylation frequency between different positions of a genome varies widely, we find a surprisingly high consistency in the methylation profile between individuals thriving in divergent ecological conditions, particularly in Heliosperma. This constitutive stability points to significant molecular or developmental constraints acting on DNA methylation variation. Altogether, by combining the flexibility of RADseq with the accuracy of bisulfite sequencing in quantifying DNA methylation, the bsRADseq methodology and our bioinformatic pipeline open up the opportunity for genome-wide epigenetic investigations of evolutionary and ecological relevance in non-model species, independent of their genomic features. PMID- 26818627 TI - Hemoglobin as a possible biochemical index of hypertension-induced vascular damage. AB - BACKGROUND: We previously reported on the positive association of hemoglobin with hypertension and atherosclerosis. On the other hand, hepatocyte growth factor (HGF) has been evaluated as a possible biochemical index of hypertension-induced vascular damage. However, no studies have reported on a correlation between hemoglobin and HGF accounting for hypertension status. METHODS: A cross-sectional study of 1108 subjects (392 men and 716 women, 40-93 years old) who were undergoing a general checkup in 2014 was conducted. RESULTS: Multiple linear regression analysis adjustment for known cardiovascular risk factors showed no significant correlation between hemoglobin and HGF in non-hypertensive subjects, but a significant positive correlation in hypertensive subjects; beta (parameter estimate) = 0.3 (p = 0.975) for non-hypertensive men, beta = 0.4 (p = 0.925) for non-hypertensive women, beta = 32.7 (p < 0.001) for hypertensive men, and beta = 18.7 (p = 0.002) for hypertensive women. CONCLUSION: We found a significant positive correlation between hemoglobin and HGF among hypertensive men and women. Like HGF, hemoglobin may be a useful indicator to evaluate hypertension-induced vascular damage. Since hemoglobin can easily be measured, these results support hemoglobin as an efficient tool to evaluate vascular damage induced by hypertension in daily medical practice. PMID- 26818628 TI - Quantitative Sensory Testing in adults with Tourette syndrome. AB - INTRODUCTION: Abnormal sensory perceptions, for instance hypersensitivity to certain external stimuli or premonitory urges preceding tics, are core features in Gilles de la Tourette syndrome (GTS). Aberrant awareness of externally applied stimuli in terms of altered sensory perception thresholds might contribute to these sensory phenomena in GTS. METHODS: We used the well-established and standardized "Quantitative Sensory Testing" (QST) battery (German Research Network on Neuropathic Pain) to investigate 13 sensory parameters including thermal, mechanical/tactile and pain thresholds in 14 GTS patients without clinically significant comorbidities and 14 healthy controls matched for age and gender. RESULTS: There were no relevant group differences in any of the 13 QST parameters and no specific QST pattern in GTS patients. There was no correlation between QST parameters and "Premonitory Urge for Tics scale" (PUTS) scores. CONCLUSION: Our data show that the perceptual threshold detection of externally applied sensory stimuli is normal in adults with GTS. This indicates that other perceptual mechanisms, such as abnormal central sensorimotor processing and/or aberrant interoceptive awareness might underlie the clinically significant sensory abnormalities in GTS. PMID- 26818629 TI - Antipsychotic utilization in the intensive care unit and in transitions of care. AB - PURPOSE: The objective of this study was to quantify the rate at which newly initiated antipsychotic therapy is continued on discharge from the intensive care unit (ICU) and describe risk factors for continuation post-ICU discharge. MATERIALS AND METHODS: This is a retrospective cohort study of all patients receiving an antipsychotic in the ICUs of a large academic medical center from January 1, 2005, to October 31, 2011. Medical record review was conducted to ascertain whether a patient was newly started on antipsychotic therapy and whether therapy was continued post-ICU discharge. RESULTS: A total of 39,248 ICU admissions over the 7-year period were evaluated. Of these, 4468 (11%) were exposed to antipsychotic therapy, of which 3119 (8%) were newly initiated. In the newly initiated cohort, 642 (21%) were continued on therapy on discharge from the hospital. Type of drug (use of quetiapine vs no use of quetiapine: odds ratio, 3.2; 95% confidence interval, 2.5-4.0; P < .0001 and use of olanzapine: odds ratio, 2.4, 95% confidence interval, 2.0-3.1; P <= .0001) was a significant risk factor for continuing antipsychotics on discharge despite adjustment for clinical factors. CONCLUSIONS: Antipsychotic use is common in the ICU setting, and a significant number of newly initiated patients have therapy continued upon discharge from the hospital. PMID- 26818630 TI - The effect of a checklist on the quality of patient handover from the operating room to the intensive care unit: A randomized controlled trial. AB - PURPOSE: Handover of patient care is a potential safety risk for the patient due to loss of information which may result in adverse outcome. We hypothesized that a checklist for handover from the operating room (OR) to the intensive care unit (ICU) will lead to an increase of quality regarding information transfer compared with a nonstandardized handover procedure. MATERIALS AND METHODS: The study was conducted as a prospective, randomized trial in a university hospital. The quality of handovers with checklist was compared with handovers without checklist. Handovers were recorded by digital voice recorder and analyzed using an individual rating sheet for each patient. This enabled to discriminate between items that "must be handed over" (red items) and items that "should be handed over" (yellow items). RESULTS: A total of 121 patient handovers from OR to ICU were included. Significantly more red items were handed over in the study group compared with the control group (study group: median 87.1%, 25-27 percentile 77.1%-90.0%; control group: median 75.0%, 25-75 percentile 66.7%-88.6%; P < .01). CONCLUSIONS: This study gives first evidence that the use of a standardized checklist for patient handover from OR to ICU increases the quantity and quality of transmitted medical information. PMID- 26818631 TI - The Global Context of Vaccine Refusal: Insights from a Systematic Comparative Ethnography of the Global Polio Eradication Initiative. AB - Many of medical anthropology's most pressing research questions require an understanding how infections, money, and ideas move around the globe. The Global Polio Eradication Initiative (GPEI) is a $9 billion project that has delivered 20 billion doses of oral polio vaccine in campaigns across the world. With its array of global activities, it cannot be comprehensively explored by the traditional anthropological method of research at one field site. This article describes an ethnographic study of the GPEI, a collaborative effort between researchers at eight sites in seven countries. We developed a methodology grounded in nuanced understandings of local context but structured to allow analysis of global trends. Here, we examine polio vaccine acceptance and refusal to understand how global phenomena-in this case, policy decisions by donors and global health organizations to support vaccination campaigns rather than building health systems-shape local behavior. PMID- 26818632 TI - Problems in the Descriptions of the Psychiatric Inclusion and Exclusion Criteria in Publications of Antidepressant Efficacy Trials: A Qualitative Review and Recommendations for Improved Clarity. AB - We recently conducted a comprehensive review of the psychiatric inclusion and exclusion criteria used in 170 placebo-controlled antidepressant efficacy trials (AETs) that were published between 1995 and 2014. In conducting this literature review, we identified a number of instances in which the descriptions of the inclusion/exclusion criteria were vague, redundant, or difficult to interpret. In the present article, we describe nine problems we encountered in our literature review. We recommend that future publications follow the examples found in a few studies in which the inclusion/exclusion criteria are clearly defined and listed in a table. PMID- 26818633 TI - Identification of the Fluvirucin B2 (Sch 38518) Biosynthetic Gene Cluster from Actinomadura fulva subsp. indica ATCC 53714: substrate Specificity of the beta Amino Acid Selective Adenylating Enzyme FlvN. AB - Fluvirucins are 14-membered macrolactam polyketides that show antifungal and antivirus activities. Fluvirucins have the beta-alanine starter unit at their polyketide skeletons. To understand the construction mechanism of the beta alanine moiety in fluvirucin biosyntheses, we have identified the biosynthetic cluster of fluvirucin B2 produced from Actinomadura fulva subsp. indica ATCC 53714. The identified gene cluster contains three polyketide synthases, four characteristic beta-amino acid-carrying enzymes, one decarboxylase, and one amidohydrolase. We next investigated the activity of the adenylation enzyme FlvN, which is a key enzyme for the selective incorporation of a beta-amino acid substrate. FlvN showed strong preference for l-aspartate over other amino acids such as beta-alanine. Based on these results, we propose a biosynthetic pathway for fluvirucin B2. PMID- 26818634 TI - The moderating role of aggressiveness in response to campaigns and interventions promoting anti-violence attitudes. AB - This research indicates that a critical factor for understanding the success or failure of anti-violence campaigns is the aggressiveness of the target audience. We propose that person and situation interact in predicting post-intervention attitudes toward violence, fighting expectations, and intentions to learn how to use real guns. Across two studies conducted in different countries and with different age populations, we found that anti-violence campaigns were effective, only for those for whom the message was already pro-attitudinal (low trait aggressiveness). In contrast, for individuals with relatively higher scores in trait aggressiveness, there was no difference in attitudes toward violence between those who received the anti-violence intervention and those assigned to the control group. In fact, the anti-violence messages resulted in a boomerang effect, increasing the favorability of attitudes toward violence in one of the studies. Aggr. Behav. 42:471-482, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26818635 TI - Ethnic identity, racial discrimination and attenuated psychotic symptoms in an urban population of emerging adults. AB - AIM: Studies suggest strong ethnic identity generally protects against negative mental health outcomes associated with racial discrimination. In light of evidence suggesting racial discrimination may enhance psychosis risk in racial and ethnic minority (REM) populations, the present study explored the relationship between ethnic identity and attenuated positive psychotic symptoms (APPS) and whether ethnic identity moderates the association between racial discrimination and these symptoms. METHODS: A sample of 644 non-help-seeking REM emerging adults was administered self-report inventories for psychosis risk, experiences of discrimination and ethnic identity. Latent class analysis was applied to determine the nature and number of ethnic identity types in this population. The direct association between ethnic identity and APPS and the interaction between ethnic identity and racial discrimination on APPS were determined in linear regression analyses. RESULTS: Results indicated three ethnic identity classes (very low, moderate to high and very high). Ethnic identity was not directly related to APPS; however, it was related to APPS under racially discriminating conditions. Specifically, participants who experienced discrimination in the moderate to high or very high ethnic identity classes reported fewer symptoms than participants who experienced discrimination in the very low ethnic identity class. CONCLUSIONS: Strong ethnic group affiliation and connection may serve a protective function for psychosis risk in racially discriminating environments and contexts among REM young adults. The possible social benefits of strong ethnic identification among REM youth who face racial discrimination should be explored further in clinical high-risk studies. PMID- 26818636 TI - Non-invasive programmed stimulation to identify high-risk patients with implanted cardioverter defibrillator (the NIPS-ICD study): study protocol for a randomized controlled trial. AB - BACKGROUND: The use of an implantable cardioverter defibrillator (ICD) is a widely used and effective therapy, which reduces the risk of cardiac death in many cardiac diseases, both implanted for secondary and primary prevention. However, recurrent arrhythmias and ICD discharges have adverse prognostic significance. Additional parameters that would identify patients who are at increased risk of arrhythmias and appropriate ICD interventions would be of clinical value. Modern ICDs are relatively complex devices with a number of functions, including the possibility to perform noninvasive programmed stimulation (NIPS) with an implanted electrode located in the right ventricle. METHODS/DESIGN: The aim of the study is to evaluate the usefulness of NIPS in determining the likelihood of life-threatening arrhythmic events in patients with ICD. The study will include 150 consecutive patients with an ICD implanted both for primary and secondary prevention, regardless of etiology, who are followed in the outpatient clinic of our center and do not meet the exclusion criteria. A 12 step St. George's Hospital NIPS protocol using ICD will be performed. The endpoint is to induce sustained ventricular arrhythmia (VT lasting more than 30 seconds or hemodynamically unstable VT/VF) or the end of the protocol. In case of serious and/or hemodynamically unstable heart rhythm disorders resistant to treatment with a low-energy antiarrhythmic pacing (ATP), the patient receives a short-term intravenous general anesthesia, and internal or external defibrillation is performed. Outpatient follow-up will be conducted during the pre-scheduled ICD control visits. An analysis of records of a registered memory device will be collected, a patient will be interviewed, and physical examination will be carried out. The follow-ups will be held every 3 months for 1 year. The primary endpoint of the follow-up will be appropriate intervention of ICD or sudden cardiac (arrhythmic) death; the secondary, appropriate ICD intervention, or death from cardiovascular causes; and the tertiary, appropriate ICD intervention, death or hospitalization for cardiovascular causes. DISCUSSION: It is expected that appropriate ICD interventions during follow-up will occur more often in patients who had sustained ventricular arrhythmias induced during NIPS. CLINICAL TRIALS REGISTRY: ClinicalTrials.gov, NCT02373306 , date of registration: 26 February 2015. PMID- 26818637 TI - Seagrass sediments reveal the long-term deterioration of an estuarine ecosystem. AB - The study of a Posidonia australis sediment archive has provided a record of ecosystem dynamics and processes over the last 600 years in Oyster Harbour (SW Australia). Ecosystem shifts are a widespread phenomenon in coastal areas, and this study identifies baseline conditions and the time-course of ecological change (cycles, trends, resilience and thresholds of ecosystem change) under environmental stress in seagrass-dominated ecosystem. The shifts in the concentrations of chemical elements, carbonates, sediments <0.125 mm and stable carbon isotope signatures (delta(13) C) of the organic matter were detected between 1850s and 1920s, whereas the shift detected in P concentration occurred several decades later (1960s). The first degradation phase (1850s-1950s) follows the onset of European settlement in Australia and was characterized by a strong increase in sediment accumulation rates and fine-grained particles, driven primarily by enhanced run-off due to land clearance and agriculture in the catchment. About 80% of total seagrass area at Oyster Harbour was lost during the second phase of environmental degradation (1960s until present). The sharp increase in P concentration and the increasing contribution of algae and terrestrial inputs into the sedimentary organic matter pool around 1960s provides compelling evidence of the documented eutrophication of the estuary and the subsequent loss of seagrass meadows. The results presented demonstrate the power of seagrass sedimentary archives to reconstruct the trajectories of anthropogenic pressures on estuarine ecosystem and the associated regime shifts, which can be used to improve the capacity of scientists and environmental managers to understand, predict and better manage ecological change in these ecosystems. PMID- 26818639 TI - Medicine's kaleidoscope: A reflection on perspectives. PMID- 26818640 TI - Botulinum toxin as a treatment for refractory overactive bladder. AB - Detrusor overactivity is the most common cause of overactive bladder (OAB) and refers to demonstrable involuntary detrusor contractions during urodynamic studies. The number of adults age 40 years or older suffering from idiopathic urge incontinence ranges from 13% in men to 30% in women. For patients whose symptoms are refractory to conventional therapy, intradetrusor botulinum toxin injection offers a safe and effective outpatient treatment with high rates of improvement of OAB symptoms. PMID- 26818642 TI - What is the appropriate duration of dual antiplatelet therapy? AB - Healthcare providers often are faced with the challenge of determining an appropriate length of dual antiplatelet therapy (DAPT) for patients who have had percutaneous coronary intervention and stent placement. This is an especially challenging clinical decision for patients with drug-eluting stents, as several studies show different results when assessing risk and benefit. PMID- 26818643 TI - A patient with Factor V Leiden and a related pulmonary embolism. AB - Venous thromboembolism (VTE) is a complication associated with the hypercoaguable state produced in patients with Factor V Leiden deficiency. Clinically, patients can present with pleuritic chest pain, dyspnea, tachycardia, and unilateral leg swelling, warmth, erythema, and pain. Treatment with heparin is urgent, and patients should continue an anticoagulation drug regimen at home. PMID- 26818644 TI - HIV pharmacotherapy: A review of integrase inhibitors. AB - Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral agents used to treat HIV. These drugs--raltegravir, elvitegravir, and dolutegravir--are preferred options for treatment-naive patients when used in combination with two nucleoside reverse transcriptase inhibitors. Based on clinical trials, INSTIs have been proven to be effective with minimal safety concerns. This article reviews the pharmacologic profile, role in therapy, and safety and efficacy of each agent. PMID- 26818645 TI - Physician assistants reduce resident workload and improve care in an academic surgical setting. AB - OBJECTIVES: Educational demands coupled with restricted hours reduce residents' availability to provide care at academic hospitals. Physician assistants (PAs) may address this issue. This study assessed the effect of PAs on patient discharges, resident workload, and resident perceptions of PAs on a surgical team. METHODS: Two PAs were employed on teams caring for complex surgical patients. Measures included time of discharge order entry, hours residents spent on the electronic medical record (EMR), and resident opinions of PA effectiveness. RESULTS: The teams with PAs had a 0.5% late discharge and 16% early discharge rate. Junior residents with a PA on the team spent fewer hours on the EMR. Residents reported PAs significantly improved their rotation and quality care. CONCLUSIONS: PAs reduce resident workload and improve care on surgical teams in a tertiary hospital. PMID- 26818646 TI - Persistent cough, chest pain, and dyspnea in a young man. PMID- 26818647 TI - Understanding the new pregnancy and lactation drug labeling. AB - Recent changes to the FDA's drug labeling rules clarify the risk of drugs for patients who are pregnant or lactating and remove A, B, C, D, and X as risk categories. Drugs are now categorized by risk for pregnancy, lactation, and women and men of reproductive potential. Risk summaries and clinical considerations in the new labeling can help prescribers and patients make informed decisions about medication use. PMID- 26818648 TI - Oral ulcers and an unusual skin rash in a teenager. PMID- 26818649 TI - When a discharge instruction is overlooked. PMID- 26818650 TI - From mercury sphygmomanometer to electric device on blood pressure measurement: correspondence of Minamata Convention on Mercury. PMID- 26818651 TI - To overcome two diseases with one pill. PMID- 26818652 TI - A sodium-glucose co-transporter 2 inhibitor empagliflozin prevents abnormality of circadian rhythm of blood pressure in salt-treated obese rats. AB - Studies were performed to examine the effects of the selective sodium-glucose co transporter 2 (SGLT2) inhibitor empagliflozin on urinary sodium excretion and circadian blood pressure in salt-treated obese Otsuka Long Evans Tokushima Fatty (OLETF) rats. Fifteen-week-old obese OLETF rats were treated with 1% NaCl (in drinking water), and vehicle (0.5% carboxymethylcellulose, n=10) or empagliflozin (10 mg kg(-1)per day, p.o., n=11) for 5 weeks. Blood pressure was continuously measured by telemetry system. Glucose metabolism and urinary sodium excretion were evaluated by oral glucose tolerance test and high salt challenge test, respectively. Vehicle-treated OLETF rats developed non-dipper type blood pressure elevation with glucose intolerance and insulin resistance. Compared with vehicle treated animals, empagliflozin-treated OLETF rats showed an approximately 1000 fold increase in urinary glucose excretion and improved glucose metabolism and insulin resistance. Furthermore, empagliflozin prevented the development of blood pressure elevation with normalization of its circadian rhythm to a dipper profile, which was associated with increased urinary sodium excretion. These data suggest that empagliflozin elicits beneficial effects on both glucose homeostasis and hypertension in salt-replete obese states. PMID- 26818653 TI - Association between a polymorphic poly-T repeat sequence in the promoter of the somatostatin gene and hypertension. AB - Despite the numerous common pathways connecting blood pressure regulation to somatostatin (SST) metabolism, the SST gene has never been seen as a significant blood pressure modulator. The aim of this study was to evaluate the association between a poly-T repeat sequence (rs34872250) in the promoter of the SST gene and blood pressure, according to the obesity status. We genotyped 1918 French Canadian subjects from a founder population. Analyses were performed according to the length of the poly-T repeat sequence on both alleles and divided into two groups, the 13/13-13/14 group and the 13/15-13/16 group. The effect of age, gender, body mass index, antihypertensive drugs and diabetic status were considered. Systolic, diastolic and mean blood pressures are significantly higher among the 13/15-13/16 group in the whole sample (P<0.05). Whereas the differences remain significant in women, they turn to be non-significant when men are considered alone. The risk of hypertension is increased in the 13/15-13/16 group, particularly among overweight/obese subjects. Systolic blood pressure is significantly higher among overweight/obese carriers of the 13/15-13/16 alleles in the whole sample (P<0.001), in men (P=0.006) and in women (P=0.002), even after correction for age and antihypertensive drugs. These results suggest that the poly-T repeat sequence polymorphism in the promoter of the SST gene is associated with significant variations of blood pressure and could modulate the risk of hypertension, particularly among women. PMID- 26818654 TI - Circadian blood pressure rhythm as a possible key target of SGLT2 inhibitors used for the treatment of Type 2 diabetes. PMID- 26818656 TI - Protein Camouflage: Supramolecular Anion Recognition by Ubiquitin. AB - Progress in the field of bio-supramolecular chemistry, the bottom-up assembly of protein-ligand systems, relies on a detailed knowledge of molecular recognition. To address this issue, we have characterised complex formation between human ubiquitin (HUb) and four supramolecular anions. The ligands were: pyrenetetrasulfonic acid (4PSA), p-sulfonato-calix[4]arene (SCLX4), bisphosphate tweezers (CLR01) and meso-tetrakis (4-sulfonatophenyl)porphyrin (TPPS), which vary in net charge, size, shape and hydrophobicity. All four ligands induced significant changes in the HSQC spectrum of HUb. Chemical shift perturbations and line-broadening effects were used to identify binding sites and to quantify affinities. Supporting data were obtained from docking simulations. It was found that these weakly interacting ligands bind to extensive surface patches on HUb. A comparison of the data suggests some general indicators for the protein-binding specificity of supramolecular anions. Differences in binding were observed between the cavity-containing and planar ligands. The former had a preference for the arginine-rich, flexible C terminus of HUb. PMID- 26818655 TI - The persisting gender gap in hypertension management and control in Germany: 1998 and 2008-2011. AB - Hypertension is a major risk factor for cardiovascular morbidity; therefore, its control is very important. International Guidelines recommend the same hypertension management in men and women; however, studies suggest that management of hypertension differs. This study explores gender-age disparities in the management and control of hypertension in Germany in 1998 and 2008-2011. Data from the German Health Examination Surveys (GNHIES98 1998, n=7124 and DEGS1 2008 2011, n=7988, age 18-79 years), including standardized blood pressure measurements and Anatomical Therapeutic Chemical medication codes, were analyzed by gender and two age groups. For 1998 and 2008-2011 in Germany, the gender gap in hypertension management persisted without significant changes. Hypertensive men in 2008-2011 had lower awareness of their condition (78.3 vs. 86.8%), less treatment for hypertension (65.3 vs. 79.2%), less control of hypertension (45.4 vs. 57.5%) and less treatment among those aware of their condition (83.9 vs. 91.5%) than did women. These gender differences were greater in younger compared with older adults (18-54 years vs. 55-79 years). No gender differences were observed in control of hypertension among those treated in 1998; however, subsequent improvement was less in younger men compared with the other age-gender groups, leading to a new gender gap in 18-54-year olds (women 84.8%, men 63.9%). Younger women used more beta-blockers and less angiotensin-converting enzyme inhibitors (ACEI) than younger men. Factors positively associated with control among those treated for hypertension in the younger group were being a woman, using beta-blockers or using ACEI, or angiotensin-receptor blockers. In the older group, diabetes was negatively associated with control of hypertension, whereas having cardiovascular comorbidities was positively associated. Gender disparities in hypertension management and control still exist in Germany but may be masked because they are age-dependent. PMID- 26818657 TI - Facile preparation of hybrid core-shell nanorods for photothermal and radiation combined therapy. AB - The hybrid platinum@iron oxide core-shell nanorods with high biocompatibility were synthesized and applied for combined therapy. These hybrid nanorods exhibit a good photothermal effect on cancer cells upon irradiation with a NIR laser. Furthermore, due to the presence of a high atomic number element (platinum core), the hybrid nanorods show a synergistic effect between photothermal and radiation therapy. Therefore, the as-prepared core-shell nanorods could play an important role in facilitating synergistic therapy between photothermal and radiation therapy to achieve better therapeutic efficacy. PMID- 26818658 TI - MicroRNA 429 Regulates Mucin Gene Expression and Secretion in Murine Model of Colitis. AB - BACKGROUND AND AIMS: miRNAs are non-coding RNAs that play important roles in the pathogenesis of human diseases by regulating target gene expression in specific cells or tissues. We aimed to detect miRNAs related to ulcerative colitis [UC], identify their target molecules, and analyse the correlation between the miRNAs and their target genes in colorectal cells and dextran sulphate sodium [DSS] induced mouse colitis. METHODS: UC-associated miRNAs were identified by miRNA microarray analysis using DSS-induced colitis and normal colon tissues. The results were validated by quantitative real-time polymerase chain reaction [RT PCR]. We identified target genes of MIR429, a colitis-associated miRNA, from our screen by comparing the mRNA microarray analysis in MIR429-overexpressed cells with predicted candidate target genes. We constructed luciferase reporter plasmids to confirm the effect of MIR429 on target gene expression. The protein expression of the target genes was measured by western blot,enzyme-linked immunosorbent assay [ELISA] analysis, or immunohistochemistry. RESULTS: We identified 37 DSS-induced colitis associated miRNAs. We investigated MIR429 that is down-regulated in DSS-induced colitis, and identified 41 target genes of MIR429. We show that the myristoylated alanine-rich protein kinase C substrate [MARCKS] is a direct target of MIR429. MARCKS mRNA and protein expression levels are down-regulated by MIR429, and MIR429 regulates the expression of MARCKS and MARCKS-mediated mucin secretion in colorectal cells and DSS-induced colitis. In addition, anti-MIR429 up-regulates MARCKS expression in colorectal cell lines. CONCLUSION: Our findings suggest that MIR429 modulates mucin secretion in human colorectal cells and mouse colitis tissues by up-regulating of MARCKS expression, thereby making MIR429 a candidate for anti-colitis therapy in human UC. PMID- 26818660 TI - Similar Short- and Long-term Colectomy Rates with Ciclosporin and Infliximab Treatment in Hospitalised Ulcerative Colitis Patients. AB - BACKGROUND AND AIMS: Ciclosporin A [CsA] and infliximab [IFX] are similarly effective in preventing short-term colectomy in ulcerative colitis [UC] patients, but long-term data are scarce. We aimed to compare short- and long-term efficacy of CsA and IFX by analysing colectomy rates and failure of remission-induction treatment as outcome parameters for treatment success. METHODS: We retrospectively studied hospitalised UC patients who received CsA or IFX for moderate-to-severe UC, between January 2000 and April 2014. The primary endpoint was time to colectomy, and treatment failure [defined as colectomy or another remission-induction treatment with corticosteroids, CsA, or IFX] was used as secondary endpoint. Variables possibly affecting colectomy outcomes were analysed. RESULTS: A total of 55 patients were studied for colectomy outcome and 58 patients for treatment failure. A significantly longer follow-up duration was available for CsA-treated patients [p < 0.001, both subcohorts]. Patients showed comparable patient- and disease-specific characteristics. Colectomy rates did not differ significantly at 3, 12, and 36 months: 36% versus 29%, 58% versus 48%, and 64% versus 67% for CsA- and IFX-treated patients, respectively. Multivariate Cox regression analysis revealed the lowest hazard ratio [HR] for colectomy in patients concomitantly using thiopurines: HR 0.28 (confidence interval [CI] 0.13 0.64), p = 0.002. Treatment failure rates were not significantly different at 3, 12 and 36 months: 35% versus 48%, 51% versus 68%, and 62% versus 83% for CsA- and IFX-treated patients, respectively. CONCLUSIONS: Treatment with CsA and IFX is similarly effective in preventing short- and long-term colectomy in hospitalised UC patients. Furthermore, failure rates of these remission-induction treatments were comparable. PMID- 26818659 TI - Safety and Efficacy of Granulocyte/Monocyte Apheresis in Steroid-Dependent Active Ulcerative Colitis with Insufficient Response or Intolerance to Immunosuppressants and/or Biologics [the ART Trial]: 12-week Interim Results. AB - BACKGROUND AND AIMS: Patients with active, steroid-dependent ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologic therapies have limited treatment options. Adacolumn, a granulocyte/monocyte adsorptive apheresis device, has shown clinical benefit in these patients. This study aimed to provide additional clinical data regarding the safety and efficacy of Adacolumn in this patient subgroup. METHODS: This single-arm, open-label, multicentre trial [ART] was conducted at 18 centres across the UK, France, and Germany. Eligible patients were 18-75 years old with moderate-to-severe, steroid dependent active ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologics. Patients received >= 5 weekly apheresis sessions with Adacolumn. The primary endpoint was clinical remission rate [clinical activity index <= 4] at Week 12. RESULTS: In all, 86 patients were enrolled. At Week 12, 33/84 [39.3%] of patients in the intention-to-treat population achieved clinical remission, with 47/84 [56.0%] achieving a clinical response [clinical activity index reduction of >= 3]. Clinical remission was achieved in 30.0% of patients with previous immunosuppressant and biologic failure; steroid-free clinical remission and response were observed in 22.6% and 35.7% of these patients, respectively. Quality of life [Short Health Scale] significantly improved at Week 12 [p < 0.0001]. The majority of adverse events were of mild/moderate intensity. CONCLUSIONS: At Week 12, Adacolumn provided significant clinical benefit in a large cohort of steroid-dependent ulcerative colitis patients with previous failure to immunosuppressant and/or biologic treatment, with a favourable safety profile. These results are consistent with previous studies and support Adacolumn use in this difficult-to-treat patient subgroup. PMID- 26818661 TI - High-resolution Quantitative Computed Tomography Demonstrates Structural Defects in Cortical and Trabecular Bone in IBD Patients. AB - BACKGROUND AND AIMS: To investigate the macro- and microstructural changes of bone in patients with inflammatory bowel disease [IBD] and to define the factors associated with bone loss in IBD. METHODS: A total of 148 subjects, 59 with Crohn's disease [CD], 39 with ulcerative colitis [UC], and 50 healthy controls were assessed for the geometric, volumetric and microstructural properties of bone using high-resolution peripheral quantitative computed tomography. In addition, demographic and disease-specific characteristics of IBD patients were recorded. RESULTS: IBD patients and controls were comparable in age, sex, and body mass index. Total [p = 0.001], cortical [p < 0.001], and trabecular volumetric bone mineral density [BMD] [p = 0.03] were significantly reduced in IBD patients compared with healthy controls. Geometric and microstructural analysis revealed significantly lower cortical area [p = 0.001] and cortical thickness [p < 0.001] without differences in cortical porosity, pore volume, or pore diameter. CD showed a more severe bone phenotype than UC: cortical bone loss was observed in both diseases, but CD additionally showed profound trabecular bone loss with reduced trabecular BMD [p = 0.008], bone volume [p = 0.008], and trabecular thickness [p = 0.009]. Multivariate regression models identified the diagnosis of CD, female sex, lower body mass index, and the lack of remission as factors independently associated with bone loss in IBD. CONCLUSION: IBD patients develop significant cortical bone loss, impairing bone strength. Trabecular bone loss is limited to CD patients, who exhibit a more severe bone phenotype compared with UC patients. PMID- 26818662 TI - Concordance in Anti-OmpC and Anti-I2 Indicate the Influence of Genetic Predisposition: Results of a European Study of Twins with Crohn's Disease. AB - BACKGROUND AND AIMS: An adaptive immunological response to microbial antigens has been observed in Crohn's disease (CD). Intriguingly, this serological response precedes the diagnosis in some patients and has also been observed in healthy relatives. We aimed to determine whether genetic factors are implicated in this response in a CD twin cohort. METHODS: In total, 82 twin pairs (Leuven n = 13, Maastricht n = 8, Orebro n = 61) took part: 81 pairs with CD (concordant monozygotic n = 16, discordant monozygotic n = 22, concordant dizygotic n = 3, discordant dizygotic n = 40) and 1 monozygotic pair with both CD and ulcerative colitis. Serology for Pseudomonas fluorescens-related protein (anti-I2), Escherichia coli outer membrane porin C (anti-OmpC), CBir1flagellin (anti-CBir1) and antibodies to oligomannan (anti-Saccharomyces cerevisiae antibody [ASCA]) was determined by standardized enzyme-linked immunoassay. RESULTS: All markers were more often present in CD twins than in their healthy twin siblings. Using the intraclass correlation coefficient (ICC), agreements in concentrations of anti OmpC and anti-I2 were observed in discordant monozygotic but not in discordant dizygotic twin pairs with CD (anti-OmpC, ICC 0.80 and -0.02, respectively) and (anti-I2, ICC 0.56 and 0.05, respectively). In contrast, no agreements were found in anti-CBir, immunoglobulin (Ig) G ASCA and ASCA IgA. CONCLUSIONS: We show that anti-I2 and anti-CBir1 statuses have specificity for CD and confirm previous reported specificities for anti-OmpC and ASCA. Based on quantitative analyses and observed ICCs, genetics seems to predispose to the anti-OmpC and anti-I2 response but less to ASCA and anti-CBir1 responses. PMID- 26818663 TI - E3 Ubiquitin ligase RNF183 Is a Novel Regulator in Inflammatory Bowel Disease. AB - BACKGROUND AND AIMS: Specific members of the RING finger [RNF] protein family serve as E3 ubiquitin ligases and play important roles in the regulation of inflammation. However, their roles in the pathogenesis of inflammatory bowel disease [IBD] have not been explored. METHODS: Genomic microarray of inflamed colon samples from Crohn's disease [CD] patients was performed to identify potential up-regulated genes. Expression of the identified highly up-regulated RNF183 gene was subsequently examined by quantitative reverse transcription polymerase chain reaction [qRT-PCR], western blotting and immunohistochemistry of the intestinal tissues of IBD patients and the colons of trinitrobenzene sulphonic acid [TNBS]-induced colitic mice. RNF183-mediated interaction with the NF-kappaB pathway and ubiquitination of IkappaBalpha were examined by siRNA, plasmid transfection, and immunoprecipitation. The miRNA predicted to target RNF183 was explored and its role in the RNF183/ NF-kappaB pathway was investigated. RESULTS: RNF183 was up-regulated in intestinal epithelial cells in IBD patients and in colitic mice. RNF183 promoted intestinal inflammation via the activation of the NF-kappaB pathway by increasing the ubiquitination and degradation of IkappaBalpha. Computational analysis identified putative binding of miR-7 to RNF183. Transfection of intestinal cells with a miR-7 mimic or inhibitor confirmed its negative regulatory effect on RNF183 expression and ubiquitination of IkappaBalpha. miR-7 was down-regulated in inflamed colon tissues of IBD patients and colitic mice. CONCLUSIONS: RNF183, which is negatively regulated by miR-7, is a novel regulator promoting intestinal inflammation by increasing the ubiquitination and degradation of IkappaBalpha, thereby inducing NF-kappaB activation. The interaction between RNF183-mediated ubiquitination and miRNA may be an important novel epigenetic mechanism in the pathogenesis of IBD. PMID- 26818664 TI - Anal Squamous Cell Carcinoma: An Infrequent Challenge in the Management of Ulcerative Colitis Under Combination Therapy. PMID- 26818665 TI - First-person Pronoun Use in Spoken Language as a Predictor of Future Depressive Symptoms: Preliminary Evidence from a Clinical Sample of Depressed Patients. AB - : Several theories suggest that self-focused attention plays an important role in the maintenance of depression. However, previous studies have predominantly relied on self-report and laboratory-based measures such as sentence completion tasks to assess individual differences in self-focus. We present a prospective, longitudinal study based on a sample of 29 inpatients with clinical depression, investigating whether an implicit, behavioural measure of self-focused attention, i.e., the relative frequency of first-person singular pronouns in naturally spoken language, predicts depressive symptoms at follow-up over and above initial depression. We did not find a significant cross-sectional association between depressive symptoms and first-person singular pronoun use. However, first-person singular pronoun use significantly predicted depressive symptoms approximately 8 months later, even after controlling for depressive symptoms at baseline or discharge. Exploratory analyses revealed that this effect was mainly driven by the use of objective and possessive self-references such as 'me' or 'my'. Our findings are in line with theories that highlight individual differences in self focused attention as a predictor of the course of depression. Moreover, our findings extend previous work in this field by adopting an unobtrusive approach of non-reactive assessment, capturing naturally occurring differences in self focused attention. We discuss possible clinical applications of language-based assessments and interventions with regard to self-focus. Copyright (c) 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Naturally occurring individual differences in first-person singular pronoun use provide an unobtrusive way to assess patients' automatic self-focused attention. Frequent use of first-person singular pronouns predicts an unfavourable course of depression. Self-focused language might offer innovative ways of tracking and targeting therapeutic change. PMID- 26818666 TI - Consolidating and Exploring Antibiotic Resistance Gene Data Resources. AB - The unrestricted use of antibiotics has resulted in rapid acquisition of antibiotic resistance (AR) and spread of multidrug-resistant (MDR) bacterial pathogens. With the advent of next-generation sequencing technologies and their application in understanding MDR pathogen dynamics, it has become imperative to unify AR gene data resources for easy accessibility for researchers. However, due to the absence of a centralized platform for AR gene resources, availability, consistency, and accuracy of information vary considerably across different databases. In this article, we explore existing AR gene data resources in order to make them more visible to the clinical microbiology community, to identify their limitations, and to propose potential solutions. PMID- 26818667 TI - Propionibacterium acnes: Disease-Causing Agent or Common Contaminant? Detection in Diverse Patient Samples by Next-Generation Sequencing. AB - Propionibacterium acnesis the most abundant bacterium on human skin, particularly in sebaceous areas.P. acnesis suggested to be an opportunistic pathogen involved in the development of diverse medical conditions but is also a proven contaminant of human clinical samples and surgical wounds. Its significance as a pathogen is consequently a matter of debate. In the present study, we investigated the presence ofP. acnesDNA in 250 next-generation sequencing data sets generated from 180 samples of 20 different sample types, mostly of cancerous origin. The samples were subjected to either microbial enrichment, involving nuclease treatment to reduce the amount of host nucleic acids, or shotgun sequencing. We detected high proportions ofP. acnesDNA in enriched samples, particularly skin tissue-derived and other tissue samples, with the levels being higher in enriched samples than in shotgun-sequenced samples.P. acnesreads were detected in most samples analyzed, though the proportions in most shotgun-sequenced samples were low. Our results show thatP. acnescan be detected in practically all sample types when molecular methods, such as next-generation sequencing, are employed. The possibility of contamination from the patient or other sources, including laboratory reagents or environment, should therefore always be considered carefully whenP. acnesis detected in clinical samples. We advocate that detection ofP. acnesalways be accompanied by experiments validating the association between this bacterium and any clinical condition. PMID- 26818668 TI - Direct Identification of Urinary Tract Pathogens from Urine Samples, Combining Urine Screening Methods and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry. AB - Early diagnosis of urinary tract infections (UTIs) is essential to avoid inadequate or unnecessary empirical antibiotic therapy. Microbiological confirmation takes 24 to 48 h. The use of screening methods, such as cytometry and automated microscopic analysis of urine sediment, allows the rapid prediction of negative samples. In addition, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) is a widely established technique in clinical microbiology laboratories used to identify microorganisms. We evaluated the ability of MALDI-TOF MS to identify microorganisms from direct urine samples and the predictive value of automated analyzers for the identification of microorganisms in urine by MALDI-TOF MS. A total of 451 urine samples from patients with suspected UTIs were first analyzed using the Sysmex UF 1000iflow cytometer, an automatic sediment analyzer with microscopy (SediMax), culture, and then processed by MALDI-TOF MS with a simple triple-centrifuged procedure to obtain a pellet that was washed and centrifuged and finally applied directly to the MALDI-TOF MS plate. The organisms in 336 samples were correctly identified, mainly those with Gram-negative bacteria (86.10%). No microorganisms were misidentified, and noCandidaspp. were correctly identified. Regarding the data from autoanalyzers, the best bacteriuria cutoffs were 1,000 and 200 U/MUl for UF-1000iand SediMax, respectively. It was concluded that the combination of a urine screening method and MALDI-TOF MS provided a reliable identification from urine samples, especially in those containing Gram-negative bacteria. PMID- 26818669 TI - Diagnosis of Bloodstream Infections in Children. AB - Identification of bloodstream infections is among the most critical tasks performed by the clinical microbiology laboratory. While the criteria for achieving an adequate blood culture specimen in adults have been well described, there is much more ambiguity in pediatric populations. This minireview focuses on the available pediatric literature pertaining to the collection of an optimal blood culture specimen, including timing, volume, and bottle selection, as well as rapid diagnostic approaches and their role in the management of pediatric bloodstream infections. PMID- 26818670 TI - Pneumococcus with the "6E" cps Locus Produces Serotype 6B Capsular Polysaccharide. AB - Genetic studies of serogroup 6 isolates ofStreptococcus pneumoniaeidentified putative serotype 6E. Although its capsular polysaccharide structure has not been elucidated, putative serotype 6E is described in an increasing number of studies as a potentially new serotype. We show here that SPEC6B, which is widely used as a target strain for serotype 6B opsonophagocytosis assays, has the genetic features of the putative serotype 6E but produces capsular polysaccharide identical to 6B capsular polysaccharide as determined by one-dimensional (1D) and 2D nuclear magnetic resonance (NMR). Thus, putative serotype 6E is a mere genetic variant of serotype 6B. Also, SPEC6B is appropriate as a target strain for serotype 6B opsonophagocytosis assays. This example illustrates the difficulties of assigning new bacterial serotypes based on genetic findings alone. PMID- 26818671 TI - Reassessment of the Role of Rapid Antigen Detection Tests in Diagnosis of Invasive Group A Streptococcal Infections. AB - Rapid antigen detection tests (RADTs) for group A streptococci (GAS) are widely used for diagnosing acute pharyngitis, which has led to a considerable reduction in antibiotic prescriptions over the past decade. Beyond this intended use, their reassessment on invasive samples may be relevant in the management of life threatening GAS infections. To this end, we evaluated the performances of three RADTs, culture, GAS PCR, and 16S rRNA gene PCR assays, and compared them with a composite gold standard (GAS-PCR assay and/or culture) for the diagnosis of severe GAS infection. A total of 192 specimens from deep-tissue (mostly normally sterile) sites enriched for 75 GAS-positive samples were enrolled in the study. The three evaluated RADTs showed sensitivities ranging from 88.0% to 94.7% versus 98.7% for GAS PCR, 84% for 16S rRNA gene PCR, and 77.3% for culture. The sensitivities of the ImmunoCardSTAT! Strep A test (Meridian Bioscience) and the NADAL Strep A strip (Nal Von Minden) were similar to that of GAS PCR (P= 0.25 and 0.03, respectively) and higher than that of culture (P= 0.001 and 0.006, respectively), whereas the SD Bioline Strep A test strip (Standard Diagnostics) showed a performance similar to that of culture (P= 0.02). The three RADTs detected 10 distinctemmtypes, including a predominance ofemm1 (33.3%),emm89 (10.6%), andemm12 (7.6%). No false-positive results were observed, leading to a specificity of 100% for all the evaluated RADTs. The GAS RADTs turned out to be sensitive, specific, and easy-to-use tools that may aid in the management of invasive GAS infections in 24/7 point-of-care laboratories by enabling early diagnosis and focused therapy. PMID- 26818673 TI - The Brief Case: a New Feature in Journal of Clinical Microbiology. PMID- 26818672 TI - Unbiased Detection of Respiratory Viruses by Use of RNA Sequencing-Based Metagenomics: a Systematic Comparison to a Commercial PCR Panel. AB - Current infectious disease molecular tests are largely pathogen specific, requiring test selection based on the patient's symptoms. For many syndromes caused by a large number of viral, bacterial, or fungal pathogens, such as respiratory tract infections, this necessitates large panels of tests and has limited yield. In contrast, next-generation sequencing-based metagenomics can be used for unbiased detection of any expected or unexpected pathogen. However, barriers for its diagnostic implementation include incomplete understanding of analytical performance and complexity of sequence data analysis. We compared detection of known respiratory virus-positive (n= 42) and unselected (n= 67) pediatric nasopharyngeal swabs using an RNA sequencing (RNA-seq)-based metagenomics approach and Taxonomer, an ultrarapid, interactive, web-based metagenomics data analysis tool, with an FDA-cleared respiratory virus panel (RVP; GenMark eSensor). Untargeted metagenomics detected 86% of known respiratory virus infections, and additional PCR testing confirmed RVP results for only 2 (33%) of the discordant samples. In unselected samples, untargeted metagenomics had excellent agreement with the RVP (93%). In addition, untargeted metagenomics detected an additional 12 viruses that were either not targeted by the RVP or missed due to highly divergent genome sequences. Normalized viral read counts for untargeted metagenomics correlated with viral burden determined by quantitative PCR and showed high intrarun and interrun reproducibility. Partial or full-length viral genome sequences were generated in 86% of RNA-seq-positive samples, allowing assessment of antiviral resistance, strain-level typing, and phylogenetic relatedness. Overall, untargeted metagenomics had high agreement with a sensitive RVP, detected viruses not targeted by the RVP, and yielded epidemiologically and clinically valuable sequence information. PMID- 26818674 TI - Development and Validation of an Improved PCR Method Using the 23S-5S Intergenic Spacer for Detection of Rickettsiae in Dermacentor variabilis Ticks and Tissue Samples from Humans and Laboratory Animals. AB - A novel nested PCR assay was developed to detectRickettsiaspp. in ticks and tissue samples from humans and laboratory animals. Primers were designed for the nested run to amplify a variable region of the 23S-5S intergenic spacer (IGS) ofRickettsiaspp. The newly designed primers were evaluated using genomic DNA from 11Rickettsiaspecies belonging to the spotted fever, typhus, and ancestral groups and, in parallel, compared to otherRickettsia-specific PCR targets (ompA,gltA, and the 17-kDa protein gene). The new 23S-5S IGS nested PCR assay amplified all 11Rickettsiaspp., but the assays employing other PCR targets did not. The novel nested assay was sensitive enough to detect one copy of a cloned 23S-5S IGS fragment from "CandidatusRickettsia amblyommii." Subsequently, the detection efficiency of the 23S-5S IGS nested assay was compared to those of the other three assays using genomic DNA extracted from 40 adultDermacentor variabilisticks. The nested 23S-5S IGS assay detectedRickettsiaDNA in 45% of the ticks, while the amplification rates of the other three assays ranged between 5 and 20%. The novel PCR assay was validated using clinical samples from humans and laboratory animals that were known to be infected with pathogenic species ofRickettsia The nested 23S-5S IGS PCR assay was coupled with reverse line blot hybridization with species-specific probes for high-throughput detection and simultaneous identification of the species ofRickettsiain the ticks. "CandidatusRickettsia amblyommii,"R. montanensis,R. felis, andR. belliiwere frequently identified species, along with some potentially novelRickettsiastrains that were closely related toR. belliiandR. conorii. PMID- 26818675 TI - Diagnostic Performance of Xpert MTB/RIF in Tuberculous Pleural Effusion: Systematic Review and Meta-analysis. AB - A systematic review investigating the role of Xpert MTB/RIF in the diagnosis of tuberculous pleural effusion (TPE) was conducted. The pooled sensitivities and specificities of Xpert MTB/RIF were 51.4% and 98.6%, respectively, with culture used as a reference standard and 22.7% and 99.8%, respectively, with a composite reference standard (CRS) used as the benchmark. Xpert MTB/RIF has low sensitivity but excellent specificity in the diagnosis of TPE. PMID- 26818676 TI - Detecting Staphylococcus aureus Virulence and Resistance Genes: a Comparison of Whole-Genome Sequencing and DNA Microarray Technology. AB - Staphylococcus aureusis a major bacterial pathogen causing a variety of diseases ranging from wound infections to severe bacteremia or intoxications. Besides host factors, the course and severity of disease is also widely dependent on the genotype of the bacterium. Whole-genome sequencing (WGS), followed by bioinformatic sequence analysis, is currently the most extensive genotyping method available. To identify clinically relevant staphylococcal virulence and resistance genes in WGS data, we developed anin silicotyping scheme for the software SeqSphere(+)(Ridom GmbH, Munster, Germany). The implemented target genes (n= 182) correspond to those queried by the IdentibacS. aureusGenotyping DNA microarray (Alere Technologies, Jena, Germany). Thein silicoscheme was evaluated by comparing the typing results of microarray and of WGS for 154 humanS. aureusisolates. A total of 96.8% (n= 27,119) of all typing results were equally identified with microarray and WGS (40.6% present and 56.2% absent). Discrepancies (3.2% in total) were caused by WGS errors (1.7%), microarray hybridization failures (1.3%), wrong prediction of ambiguous microarray results (0.1%), or unknown causes (0.1%). Superior to the microarray, WGS enabled the distinction of allelic variants, which may be essential for the prediction of bacterial virulence and resistance phenotypes. Multilocus sequence typing clonal complexes and staphylococcal cassette chromosomemecelement types inferred from microarray hybridization patterns were equally determined by WGS. In conclusion, WGS may substitute array-based methods due to its universal methodology, open and expandable nature, and rapid parallel analysis capacity for different characteristics in once-generated sequences. PMID- 26818678 TI - Is the Presence of Actinomyces spp. in Blood Culture Always Significant? AB - The isolation ofActinomycesspp. from sterile clinical samples is traditionally regarded as significant. We reviewed the demographic characteristics, clinical risk factors, and outcomes of patients withActinomycesspp. isolated from blood cultures in our NHS Trust and found that this is not necessarily the case. PMID- 26818677 TI - Development and Validation of a Highly Accurate Quantitative Real-Time PCR Assay for Diagnosis of Bacterial Vaginosis. AB - Bacterial vaginosis (BV) is the most common gynecological infection in the United States. Diagnosis based on Amsel's criteria can be challenging and can be aided by laboratory-based testing. A standard method for diagnosis in research studies is enumeration of bacterial morphotypes of a Gram-stained vaginal smear (i.e., Nugent scoring). However, this technique is subjective, requires specialized training, and is not widely available. Therefore, a highly accurate molecular assay for the diagnosis of BV would be of great utility. We analyzed 385 vaginal specimens collected prospectively from subjects who were evaluated for BV by clinical signs and Nugent scoring. We analyzed quantitative real-time PCR (qPCR) assays on DNA extracted from these specimens to quantify nine organisms associated with vaginal health or disease:Gardnerella vaginalis,Atopobium vaginae, BV-associated bacteria 2 (BVAB2, an uncultured member of the orderClostridiales),Megasphaeraphylotype 1 or 2,Lactobacillus iners,Lactobacillus crispatus,Lactobacillus gasseri, andLactobacillus jensenii We generated a logistic regression model that identifiedG. vaginalis,A. vaginae, andMegasphaeraphylotypes 1 and 2 as the organisms for which quantification provided the most accurate diagnosis of symptomatic BV, as defined by Amsel's criteria and Nugent scoring, with 92% sensitivity, 95% specificity, 94% positive predictive value, and 94% negative predictive value. The inclusion ofLactobacillusspp. did not contribute sufficiently to the quantitative model for symptomatic BV detection. This molecular assay is a highly accurate laboratory tool to assist in the diagnosis of symptomatic BV. PMID- 26818679 TI - Cardiac expression of the CREM repressor isoform CREM-IbDeltaC-X in mice leads to arrhythmogenic alterations in ventricular cardiomyocytes. AB - Chronic beta-adrenergic stimulation is regarded as a pivotal step in the progression of heart failure which is associated with a high risk for arrhythmia. The cAMP-dependent transcription factors cAMP-responsive element binding protein (CREB) and cAMP-responsive element modulator (CREM) mediate transcriptional regulation in response to beta-adrenergic stimulation and CREM repressor isoforms are induced after stimulation of the beta-adrenoceptor. Here, we investigate whether CREM repressors contribute to the arrhythmogenic remodeling in the heart by analyzing arrhythmogenic alterations in ventricular cardiomyocytes (VCMs) from mice with transgenic expression of the CREM repressor isoform CREM-IbDeltaC-X (TG). Patch clamp analyses, calcium imaging, immunoblotting and real-time quantitative RT-PCR were conducted to study proarrhythmic alterations in TG VCMs vs. wild-type controls. The percentage of VCMs displaying spontaneous supra threshold transient-like Ca(2+) releases was increased in TG accompanied by an enhanced transduction rate of sub-threshold Ca(2+) waves into these supra threshold events. As a likely cause we discovered enhanced NCX-mediated Ca(2+) transport and NCX1 protein level in TG. An increase in I NCX and decrease in I to and its accessory channel subunit KChIP2 was associated with action potential prolongation and an increased proportion of TG VCMs showing early afterdepolarizations. Finally, ventricular extrasystoles were augmented in TG mice underlining the in vivo relevance of our findings. Transgenic expression of CREM-IbDeltaC-X in mouse VCMs leads to distinct arrhythmogenic alterations. Since CREM repressors are inducible by chronic beta-adrenergic stimulation our results suggest that the inhibition of CRE-dependent transcription contributes to the formation of an arrhythmogenic substrate in chronic heart disease. PMID- 26818680 TI - Bio-inspired Plasmonic Nanoarchitectured Hybrid System Towards Enhanced Far Red to-Near Infrared Solar Photocatalysis. AB - Solar conversion to fuels or to electricity in semiconductors using far red-to near infrared (NIR) light, which accounts for about 40% of solar energy, is highly significant. One main challenge is the development of novel strategies for activity promotion and new basic mechanisms for NIR response. Mother Nature has evolved to smartly capture far red-to-NIR light via their intelligent systems due to unique micro/nanoarchitectures, thus motivating us for biomimetic design. Here we report the first demonstration of a new strategy, based on adopting nature's far red-to-NIR responsive architectures for an efficient bio-inspired photocatalytic system. The system is constructed by controlled assembly of light harvesting plasmonic nanoantennas onto a typical photocatalytic unit with butterfly wings' 3D micro/nanoarchitectures. Experiments and finite-difference time-domain (FDTD) simulations demonstrate the structural effects on obvious far red-to-NIR photocatalysis enhancement, which originates from (1) Enhancing far red-to-NIR (700~1200 nm) harvesting, up to 25%. (2) Enhancing electric-field amplitude of localized surface plasmon (LSPs) to more than 3.5 times than that of the non-structured one, which promotes the rate of electron-hole pair formation, thus substantially reinforcing photocatalysis. This proof-of-concept study provides a new methodology for NIR photocatalysis and would potentially guide future conceptually new NIR responsive system designs. PMID- 26818682 TI - Religion, Purpose in Life, Social Support, and Psychological Distress in Chinese University Students. AB - We examined the relationship between religious involvement and psychological distress and explored the mediating effects of social support and purpose in life in university students in western, mid-western, and eastern China. Cross sectional survey of a representative sample of 1812 university students was conducted. The Purpose in Life scale, Duke Social Support Index, and Religious Commitment Inventory-10 were administered, along with Kessler's Psychological Distress Scale. Structural equation modeling was used to test two models of the mediation hypothesis, examining direct, indirect, and total effects. Model 1 (with direction of effect hypothesized from religiosity to psychological distress) indicated that religious involvement had a direct effect on increasing psychological distress (beta = 0.23, p < .01) with minor mediated effects. However, Model 2 (with direction of effect hypothesized from psychological distress to religiosity) indicated strong indirect protective effects of religiosity on psychological distress through purpose in life and social support (beta = -.40, p < .01). The findings are consistent with the hypothesis that psychological distress increases religious involvement, which then increases purpose in life and social support that then lead to lower psychological distress. PMID- 26818681 TI - Chronic administration of isocarbophos induces vascular cognitive impairment in rats. AB - Vascular dementia, being the most severe form of vascular cognitive impairment (VCI), is caused by cerebrovascular disease. Whether organophosphorus causes VCI remains unknown. Isocarbophos (0.5 mg/kg per 2 days) was intragastrically administrated to rats for 16 weeks. The structure and function of cerebral arteries were assayed. The learning and memory were evaluated by serial tests of step-down, step-through and morris water maze. Long-term administration of isocarbophos reduced the hippocampal acetylcholinesterase (AChE) activity and acetylcholine (ACh) content but did not alter the plasma AChE activity, and significantly damaged the functions of learning and memory. Moreover, isocarbophos remarkably induced endothelial dysfunction in the middle cerebral artery and the expressions of ICAM-1 and VCAM-1 in the posterior cerebral artery. Morphological analysis by light microscopy and electron microscopy indicated disruptions of the hippocampus and vascular wall in the cerebral arteries from isocarbophos-treated rats. Treatment of isocarbophos injured primary neuronal and astroglial cells isolated from rats. Correlation analysis demonstrated that there was a high correlation between vascular function of cerebral artery and hippocampal AChE activity or ACh content in rats. In conclusion, chronic administration of isocarbophos induces impairments of memory and learning, which is possibly related to cerebral vascular dysfunction. PMID- 26818684 TI - The Geography of Mental Health and General Wellness in Galveston Bay After Hurricane Ike: A Spatial Epidemiologic Study With Longitudinal Data. AB - OBJECTIVES: To demonstrate a spatial epidemiologic approach that could be used in the aftermath of disasters to (1) detect spatial clusters and (2) explore geographic heterogeneity in predictors for mental health and general wellness. METHODS: We used a cohort study of Hurricane Ike survivors (n=508) to assess the spatial distribution of postdisaster mental health wellness (most likely resilience trajectory for posttraumatic stress symptoms [PTSS] and depression) and general wellness (most likely resilience trajectory for PTSS, depression, functional impairment, and days of poor health) in Galveston, Texas. We applied the spatial scan statistic (SaTScan) and geographically weighted regression. RESULTS: We found spatial clusters of high likelihood wellness in areas north of Texas City and spatial concentrations of low likelihood wellness in Galveston Island. Geographic variation was found in predictors of wellness, showing increasing associations with both forms of wellness the closer respondents were located to Galveston City in Galveston Island. CONCLUSIONS: Predictors for postdisaster wellness may manifest differently across geographic space with concentrations of lower likelihood wellness and increased associations with predictors in areas of higher exposure. Our approach could be used to inform geographically targeted interventions to promote mental health and general wellness in disaster-affected communities. PMID- 26818683 TI - Web-Based and Mobile Stress Management Intervention for Employees: A Randomized Controlled Trial. AB - BACKGROUND: Work-related stress is highly prevalent among employees and is associated with adverse mental health consequences. Web-based interventions offer the opportunity to deliver effective solutions on a large scale; however, the evidence is limited and the results conflicting. OBJECTIVE: This randomized controlled trial evaluated the efficacy of guided Web- and mobile-based stress management training for employees. METHODS: A total of 264 employees with elevated symptoms of stress (Perceived Stress Scale-10, PSS-10>=22) were recruited from the general working population and randomly assigned to an Internet-based stress management intervention (iSMI) or waitlist control group. The intervention (GET.ON Stress) was based on Lazarus's transactional model of stress, consisted of seven sessions, and applied both well-established problem solving and more recently developed emotion regulation strategies. Participants also had the opportunity to request automatic text messages on their mobile phone along with the iSMI. Participants received written feedback on every completed session from an e-coach. The primary outcome was perceived stress (PSS-10). Web based self-report assessments for both groups were scheduled at baseline, 7 weeks, and 6 months. At 12 months, an extended follow-up was carried out for the iSMI group only. RESULTS: An intention-to-treat analysis of covariance revealed significantly large effect differences between iSMI and waitlist control groups for perceived stress at posttest (F1,261=58.08, P<.001; Cohen's d=0.83) and at the 6-month follow-up (F1,261=80.17, P<.001; Cohen's d=1.02). The effects in the iSMI group were maintained at 12-month follow-up. CONCLUSIONS: This Web- and mobile-based intervention has proven effective in reducing stress in employees in the long term. Internet-based stress management interventions should be further pursued as a valuable alternative to face-to-face interventions. TRIAL REGISTRATION: German Clinical Trials Register (DRKS): 00004749; http://drks neu.uniklinik-freiburg.de/ drks_web/setLocale_EN.do (Archived by WebCite at http://www.webcitation.org/6e8rl98nl). PMID- 26818685 TI - A full Bayesian partition model for identifying hypo- and hyper-methylated loci from single nucleotide resolution sequencing data. AB - BACKGROUD: DNA methylation is an epigenetic modification that plays important roles on gene regulation. Study of whole-genome bisulfite sequencing and reduced representation bisulfite sequencing brings the availability of DNA methylation at single CpG resolution. The main interest of study on DNA methylation data is to test the methylation difference under two conditions of biological samples. However, the high cost and complexity of this sequencing experiment limits the number of biological replicates, which brings challenges to the development of statistical methods. RESULTS: Bayesian modeling is well known to be able to borrow strength across the genome, and hence is a powerful tool for high dimensional-low-sample-size data. In order to provide accurate identification of methylation loci, especially for low coverage data, we propose a full Bayesian partition model to detect differentially methylated loci under two conditions of scientific study. Since hypo-methylation and hyper-methylation have distinct biological implication, it is desirable to differentiate these two types of differential methylation. The advantage of our Bayesian model is that it can produce one-step output of each locus being either equal-, hypo- or hyper methylated locus without further post-hoc analysis. An R package named as MethyBayes implementing the proposed full Bayesian partition model will be submitted to the bioconductor website upon publication of the manuscript. CONCLUSIONS: The proposed full Bayesian partition model outperforms existing methods in terms of power while maintaining a low false discovery rate based on simulation studies and real data analysis including bioinformatics analysis. PMID- 26818687 TI - Aberrant cervical vasculature anastomosis as cause of neck pain and successful treatment with embolization technique. AB - We report a patient with non-dermatomal radiating neck pain without focal neurologic deficit. Traditional workup could not identify an anatomic or biomechanical cause. Imaging showed a deep cervical vessel centered in the region of pain. Angiography later identified an aberrant anastomosis of this vessel with the occipital artery. Subsequent endovascular embolization of this arterial trunk resulted in complete pain relief. PMID- 26818686 TI - Lysinibacillus xyleni sp. nov., isolated from a bottle of xylene. AB - A Gram-staining-positive, solvent-tolerating (acetophenone, benzene, toluene, xylene and hexane), aerobic, non-motile, terminal endospore-forming, rod-shaped bacterium was isolated from a bottle of xylene. The strain, designated JC22(T), was found to be oxidase and catalase positive. The strain was able to tolerate solvents with different log p values like acetophenone (log P = 1.5), benzene (log P = 2.0), toluene (log P = 2.5), xylene (log P = 3.2) and hexane (log P = 3.4), though it could not use them as sole carbon sources. Based on the 16S rRNA gene sequence analysis, strain JC22(T) was identified as belonging to the genus Lysinibacillus and was most closely related to Lysinibacillus sinduriensis BLB 1(T) (98.1 %), Lysinibacillus halotolerans LAM612(T) (97.8 %), Lysinibacillus chungkukjangi 2RL3-2(T) (97.6 %) and Lysinibacillus xylanilyticus XDB9(T) (97.1 %). The DNA-DNA relatedness of strain JC22(T) with the type strains of closest species was <30 %. Strain JC22(T) grew chemoorganoheterotrophically with an optimal pH of 7-8 (range 6-10) at 35-37 degrees C (range 25-40 degrees C). The DNA G+C content was 41.2 mol%. The major cellular fatty acids were iso-C15:0, anteiso-C15:0 and iso-C16:0. Cell wall peptidoglycan type was determined to be A4alpha (L-Lys-D-Asp). Predominant quinone system was MK-7 with moderate amounts of MK-6, MK-6(H2) and MK-7(H2). Polar lipids of strain JC22(T) contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unidentified phospholipid. On the basis of morphological, physiological, genetic, phylogenetic and chemotaxonomical analyses, we conclude that strain JC22(T) be assigned the status of novel species of the genus Lysinibacillus for which the name Lysinibacillus xyleni sp. nov. is proposed. Type strain of the species is JC22(T) (= CCUG 57912(T) = KCTC 13604(T) = NBRC 105753(T) = DSM 23555(T)). PMID- 26818688 TI - Is constipation a trivial matter? AB - Constipation is a common symptom of patients presenting to the emergency department. If poorly managed, it can have significant consequences. A 50-year old man was admitted to the emergency department following cardiac arrest. His medical history included a diagnosis of cerebral palsy and multiple admissions to hospital with constipation. Clinical examination revealed a grossly distended and tense abdomen. Circulatory supply to the lower limbs was acutely impaired. CT scan revealed massive dilation of the large bowel due to faecal loading with compromised circulation to the lower limbs. Despite aggressive attempts at resuscitation, the patient continued to deteriorate and passed away. On reflection, a diagnosis of abdominal compartment syndrome secondary to severe constipation was made. This case highlights the vigilance required when managing what is often felt to be a trivial complaint and the considerable consequences when there is a failure to do so. PMID- 26818689 TI - Unusual presentation of bladder cancer resurgence and efficacy of radiotherapy. AB - A 68-year-old man with a history of bladder cancer presented with perineal pain and penile priapism. The work up showed multiple lesions strictly located in the penis; biopsy confirmed metastases of bladder cancer. Surgery was judged unfeasible and chemotherapy failed to improve symptoms. Radiotherapy was therefore delivered on the whole penis and resulted in a rapid clinical benefit and persistent control of the disease. Penile metastases are very rare and no consensus exists concerning their management; radiotherapy appears as a promising therapeutic option not only to palliate pain but also to control the disease. PMID- 26818690 TI - Necrotic lipoma at the posterior thigh mimicking liposarcoma. AB - A lipoma is one of the most common benign tumours and can develop at any location in the body. Lipomas present characteristic imaging features; hence, they are easy to identify on CT and MRI. However, cases of necrotic lipoma are rarely encountered; therefore, information on the imaging findings of necrotic lipomas is scarce. In the present report, we describe the case of a 63-year-old man with necrotic lipoma in the deep layer of the posterior thigh, which resembled a liposarcoma on imaging. To the best of our knowledge, only a few reports on necrotic lipoma on the extremities have been published. PMID- 26818691 TI - Thoracic spondylodiscitis presenting as abdominal pain. AB - A 42-year-old woman presented to our hospital with weeks of worsening pain around her lower ribs. Preceding this, she was managed in primary care with anti inflammatory drugs and physiotherapy for presumed costochondritis. Assessment in accident and emergency suggested a tender right upper quadrant with fever and neutrophilia. A surgical review of the patient was requested to assess for cholecystitis or delayed pancreatitis. On direct questioning, the patient's back pain was the predominating symptom with no neurological deficit. To assess for delayed pancreatitis, CT imaging was obtained, demonstrating unremarkable intra abdominal organs. There was also the incidental finding of thickened prevertebral soft tissues anterior to T9 and T10 vertebrae, with vertebral endplate irregularity locally. Subsequent MRI demonstrated typical appearances of infective spondylodiscitis at this level. The patient made a good recovery with intravenous antimicrobials. This case highlights how vertebrodiscitis can present insidiously and unexpectedly, manifesting as abdominal pain. PMID- 26818692 TI - Egg yolk in the eye: an ultrawide field evaluation. PMID- 26818693 TI - Serum vitamin D level and its relation with carotid intima-media thickness in type 2 diabetic patients: a cross-sectional observational study. PMID- 26818694 TI - beta-Hydroxyacyl-acyl Carrier Protein Dehydratase (FabZ) from Francisella tularensis and Yersinia pestis: Structure Determination, Enzymatic Characterization, and Cross-Inhibition Studies. AB - The bacterial system for fatty acid biosynthesis (FAS) contains several enzymes whose sequence and structure are highly conserved across a vast array of pathogens. This, coupled with their low homology and difference in organization compared to the equivalent system in humans, makes the FAS pathway an excellent target for antimicrobial drug development. To this end, we have cloned, expressed, and purified the beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ) from both Francisella tularensis (FtFabZ) and Yersinia pestis (YpFabZ). We also solved the crystal structures and performed an enzymatic characterization of both enzymes and several mutant forms of YpFabZ. Additionally, we have discovered two novel inhibitors of FabZ, mangostin and stictic acid, which show similar potencies against both YpFabZ and FtFabZ. Lastly, we selected several compounds from the literature that have been shown to be active against single homologues of FabZ and tested them against both YpFabZ and FtFabZ. These results have revealed clues as to which scaffolds are likely to lead to broad-spectrum antimicrobials targeted against FabZ as well as modifications to existing FabZ inhibitors that may improve potency. PMID- 26818695 TI - US Surgeons' Perceptions of Racial/Ethnic Disparities in Health Care: A Cross sectional Study. PMID- 26818696 TI - A titanium nitride nanotube array for potentiometric sensing of pH. AB - A titanium nitride nanotube array (TiN NTA) electrode was fabricated through anodic oxidation of titanium and reduction and nitridation of TiO2 NTA. The microstructure of TiN NTA was characterized to be uniform with inner diameters of about 120 nm, a wall thickness of 15-20 nm and an average length of 10 MUm. Open circuit potentials were measured to evaluate the TiN TNA electrode related to pH sensitivity, response time, stability, selectivity, hysteresis and reproducibility in the pH range of 2.0-11.0 at 20 +/- 1 degrees C. The prepared TiN NTA electrode exhibits a near-Nernstian slope of 55.33 mV per pH with the correlation coefficient value of 0.995. It shows good selectivity for H(+) ions in the presence of cations and anions, especially in fluoride-containing media. It also has good stability and reproducibility with a response time of 4.4 s. These make it a promising candidate as a pH electrode sensor. PMID- 26818697 TI - Probing into the binding interaction between medroxyprogesterone acetate and bovine serum albumin (BSA): spectroscopic and molecular docking methods. AB - To further understand the mechanism of action and pharmacokinetics of medroxyprogesterone acetate (MPA), the binding interaction of MPA with bovine serum albumin (BSA) under simulated physiological conditions (pH 7.4) was studied using fluorescence emission spectroscopy, synchronous fluorescence spectroscopy, circular dichroism and molecular docking methods. The experimental results reveal that the fluorescence of BSA quenches due to the formation of MPA-BSA complex. The number of binding sites (n) and the binding constant for MPA-BSA complex are ~1 and 4.6 * 10(3) M(-1) at 310 K, respectively. However, it can be concluded that the binding process of MPA with BSA is spontaneous and the main interaction forces between MPA and BSA are van der Waals force and hydrogen bonding interaction due to the negative values of DeltaG(0) , DeltaH(0) and DeltaS(0) in the binding process of MPA with BSA. MPA prefers binding on the hydrophobic cavity in subdomain IIIA (site II'') of BSA resulting in a slight change in the conformation of BSA, but BSA retaining the alpha-helix structure. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26818698 TI - A Peptide-Based Mechano-sensitive, Proteolytically Stable Hydrogel with Remarkable Antibacterial Properties. AB - A long-chain amino acid containing dipeptide has been found to form a hydrogel in phosphate buffer whose pH ranges from 6.0 to 8.8. The hydrogel formed at pH 7.46 has been characterized by small-angle X-ray scattering (SAXS), wide-angle powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR) spectroscopy, field emission scanning electron microscopy (FE-SEM), high-resolution transmission electron microscopy (HR-TEM) imaging and rheological analyses. The microscopic imaging studies suggest the formation of a nanofibrillar three-dimensional (3D) network for the hydrogel. As observed visually and confirmed rheologically, the hydrogel at pH 7.46 exhibits thixotropy. This thixotropic property can be exploited to inject the peptide. Furthermore, the hydrogel exhibits remarkable antibacterial activity against Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, which are responsible for many common diseases. The hydrogel has practical applicability due to its biocompatibility with human red blood cells and human fibroblast cells. Interestingly, this hydrogel shows high resistance toward proteolytic enzymes, making it a new potential antimicrobial agent for future applications. It has also been observed that a small change in molecular structure of the gelator peptide not only turns the gelator into a nongelator molecule under similar conditions, but it also has a significant negative impact on its bactericidal character. PMID- 26818699 TI - High throughput preparation of fly genomic DNA in 96-well format using a paint shaker. AB - Sample homogenization is an essential step for genomic DNA extraction, with multiple downstream applications in Molecular Biology. Genotyping hundreds or thousands of samples requires an automation of this homogenization step, and high throughput homogenizer equipment currently costs 7000 euros or more. We present an apparatus for homogenization of individual Drosophila adult flies in 96-well micro-titer dishes, which was built from a small portable paint-shaker (F5 portable paint-shaker, Ushake). Single flies are disrupted in each well that contains extraction buffer and a 4-mm metal ball. Our apparatus can hold up to five 96-well micro-titer plates. Construction of the homogenizer apparatus takes about 3-4 days, and all equipment can be obtained from a home improvement store. The total material cost is approximately 700 euros including the paint-shaker. We tested the performance of our apparatus using the ZR-96 Quick-gDNATM kit (Zymo Research) homogenization buffer and achieved nearly complete tissue homogenization after 15 minutes of shaking. PCR tests did not detect any cross contamination between samples of neighboring wells. We obtained on average 138 ng of genomic DNA per fly, and DNA quality was adequate for standard PCR applications. In principle, our tissue homogenizer can be used for isolation of DNA suitable for library production and high throughput genotyping by Multiplexed Shotgun Genotyping (MSG), as well as RNA isolation from single flies. The sample adapter can also hold and shake other items, such as centrifuge tubes (15-50 mL) or small bottles. PMID- 26818701 TI - Bazedoxifene, a new orphan drug for the treatment of bleeding in hereditary haemorrhagic telangiectasia. AB - Hereditary haemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber syndrome, is a dominant genetic vascular disorder. In HHT, blood vessels are weak and prone to bleeding, leading to epistaxis and anaemia, severely affecting patients' quality of life. Development of vascular malformations in HHT patients is originated mainly by mutations in ACVRL1/ALK1 (activin receptor-like kinase type I) or Endoglin (ENG) genes. These genes encode proteins of the TGF-beta signalling pathway in endothelial cells, controlling angiogenesis. Haploinsufficiency of these proteins is the basis of HHT pathogenicity. It was our objective to study the efficiency of Bazedoxifene, a selective estrogen receptor modulator (SERM) in HHT, looking for a decrease in epistaxis, and understanding the underlying molecular mechanism. Plasma samples of five HHT patients were collected before, and after 1 and 3 months of Bazedoxifene treatment. ENG and ALK1 expression in activated mononuclear cells derived from blood, as well as VEGF plasma levels, were measured. Quantification of Endoglin and ALK1 mRNA was done in endothelial cells derived from HHT and healthy donors, after in vitro treatment with Bazedoxifene. Angiogenesis was also measured by tubulogenesis and wound healing assays. Upon Bazedoxifene treatment, haemoglobin levels of HHT patients increased and the quantity and frequency of epistaxis decreased. Bazedoxifene increased Endoglin and ALK1 mRNA levels, in cells derived from blood samples and in cultured endothelial cells, promoting tube formation. In conclusion, Bazedoxifene seems to decrease bleeding in HHT by partial compensation of haploinsufficiency. The results shown here are the basis of a new orphan drug designation for HHT by the European Medicine Agency (EMA). PMID- 26818702 TI - Synthesis, characterization and biological evaluation of novel Ru(II)-arene complexes containing intercalating ligands. AB - Three new ruthenium(II)-arene complexes, namely [(eta(6)-p cymene)Ru(Me2dppz)Cl]PF6 (1), [(eta(6)-benzene)Ru(Me2dppz)Cl]PF6 (2) and [(eta(6) p-cymene)Ru(aip)Cl]PF6 (3) (Me2dppz=11,12-dimethyldipyrido[3,2-a:2',3' c]phenazine; aip=2-(9-anthryl)-1H-imidazo[4,5-f] [1,10] phenanthroline) have been synthesized and characterized using different spectroscopic techniques including elemental analysis. The complexes were found to be well soluble and stable in DMSO. The biological activity of the three complexes was tested in three different human cancer cell lines (A549, MDA-MB-231 and HeLa) and in one human non-cancerous cell line (MRC-5). Complexes 1 and 3, carrying eta(6)-p-cymene as the arene ligand, were shown to be toxic in all cell lines in the low micromolar/subnanomolar range, with complex 1 being the most cytotoxic complex of the series. Flow cytometry analysis revealed that complex 1 caused concentration- and time-dependent arrest of the cell cycle in G2-M and S phases in HeLa cells. This event is followed by the accumulation of the sub-G1 DNA content after 48h, in levels higher than cisplatin and in the absence of phosphatidylserine externalization. Fluorescent microscopy and acridine orange/ethidium bromide staining revealed that complex 1 induced both apoptotic and necrotic cell morphology characteristics. Drug-accumulation and DNA-binding studies performed by inductively coupled plasma mass spectrometry in HeLa cells showed that the total ruthenium uptake increased in a time- and concentration-dependent manner, and that complex 1 accumulated more efficiently than cisplatin at equimolar concentrations. The introduction of a Me2dppz ligand into the ruthenium(II)-p cymene scaffold was found to allow the discovery of a strongly cytotoxic complex with significantly higher cellular uptake and DNA-binding properties than cisplatin. PMID- 26818703 TI - Protein-losing enteropathy and erythema caused by egg allergy in a breast-fed infant. AB - A 4-month-old breast-fed girl presented with poor weight gain, and had edema and repeated erythema from 5 months of age. The diagnosis of protein-losing enteropathy (PLE) was confirmed on 99m Tc-labeled human serum albumin scintigraphy. Specific IgE radioallergosorbent test was class 3 for egg white, class 2 for egg yolk, and negative for other foods. Elimination of egg from the mother's diet and oral epinastine hydrochloride treatment and sodium cromolyn improved hypoalbuminemia, hypogammaglobulinemia, and erythema. PLE and erythema coincident in a breast-fed infant suggests that IgE-mediated allergy may play a leading role in some cases of PLE due to food allergy in infants. PMID- 26818700 TI - Analysis of single nucleic acid molecules in micro- and nano-fluidics. AB - Nucleic acid analysis has enhanced our understanding of biological processes and disease progression, elucidated the association of genetic variants and disease, and led to the design and implementation of new treatment strategies. These diverse applications require analysis of a variety of characteristics of nucleic acid molecules: size or length, detection or quantification of specific sequences, mapping of the general sequence structure, full sequence identification, analysis of epigenetic modifications, and observation of interactions between nucleic acids and other biomolecules. Strategies that can detect rare or transient species, characterize population distributions, and analyze small sample volumes enable the collection of richer data from biosamples. Platforms that integrate micro- and nano-fluidic operations with high sensitivity single molecule detection facilitate manipulation and detection of individual nucleic acid molecules. In this review, we will highlight important milestones and recent advances in single molecule nucleic acid analysis in micro- and nano-fluidic platforms. We focus on assessment modalities for single nucleic acid molecules and highlight the role of micro- and nano-structures and fluidic manipulation. We will also briefly discuss future directions and the current limitations and obstacles impeding even faster progress toward these goals. PMID- 26818704 TI - Complex interaction between dengue virus replication and expression of miRNA 133a. AB - BACKGROUND: Dengue virus (DENV) is the most common vector-borne viral infection worldwide with approximately 390 million cases and 25,000 reported deaths each year. MicroRNAs (miRNAs) are small non-coding RNA molecules responsible for the regulation of gene expression by repressing mRNA translation or inducing mRNA degradation. Although miRNAs possess antiviral activity against many mammalian infecting viruses, their involvement in DENV replication is poorly understood. METHODS: Here, we explored the relationship between DENV and cellular microRNAs using bioinformatics tools. We overexpressed miRNA-133a in Vero cells to test its role in DENV replication and analyzed its expression using RT-qPCR. Furthermore, the expression of polypyrimidine tract binding protein (PTB), a protein involved in DENV replication, was analyzed by western blot. In addition, we profiled miRNA 133a expression in Vero cells challenged with DENV-2, using Taqman miRNA. RESULTS: Bioinformatic analysis revealed that the 3' untranslated region (3'UTR) of the DENV genome of all four DENV serotypes is targeted by several cellular miRNAs, including miRNA-133a. We found that overexpression of synthetic miRNA 133a suppressed DENV replication. Additionally, we observed that PTB transcription , a miRNA-133a target, is down-regulated during DENV infection. Based in our results we propose that 3'UTR of DENV down-regulates endogenous expression of miRNA-133a in Vero cells during the first hours of infection. CONCLUSIONS: miRNA-133a regulates DENV replication possibly through the modulation of a host factor such as PTB. Further investigations are needed to verify whether miRNA-133a has an anti-DENV effect in vivo. PMID- 26818706 TI - Outcomes and nursing workload related to obese patients in the intensive care unit. AB - OBJECTIVES: To compare the morbidity and mortality of patients with a body mass index (BMI) < and >=30kg/m(2) and to identify risk factors related to death and length of stay of obese patients in the intensive care unit (ICU). METHODS: Prospective and cross-sectional study. SETTING: A 35-bed mixed ICU in Sao Paulo, Brazil. RESULTS: The sample consisted of 530 patients, of which 105 (19.8%) had a BMI >=30kg/m(2). A significantly higher number of obese patients were female (p=0.025). The mortality, morbidity and nursing workload were not different between the obese and nonobese groups. However, the morbidly obese patients were younger (p<0.001), had a lower Charlson Comorbidity Index (CI; p=0.002), lower Simplified Acute Physiology Score 3 (SAPS 3; p=0.047), lower Sepsis-related Organ Failure Assessment (SOFA) score (p=0.019), shorter ICU length of stay (LOS; p=0.015) and hospital LOS (p=0.039), and an increased mean nursing workload (Nursing Activities Score (NAS; p=0.004)). The SOFA score and nursing workload were identified as risk factors associated with death in the ICU. These two variables, in addition to the admission category and duration of mechanical ventilation (MV), were also related to the ICU LOS, which demonstrates an inverse relationship between the NAS and LOS. CONCLUSION: Although the morbidity, mortality and nursing workload were not significantly different between the obese and nonobese groups, our results contribute additional information to the relationship between obesity and clinical discharge and inform future research. PMID- 26818705 TI - Serotonin neurons in the dorsal raphe nucleus encode reward signals. AB - The dorsal raphe nucleus (DRN) is involved in organizing reward-related behaviours; however, it remains unclear how genetically defined neurons in the DRN of a freely behaving animal respond to various natural rewards. Here we addressed this question using fibre photometry and single-unit recording from serotonin (5-HT) neurons and GABA neurons in the DRN of behaving mice. Rewards including sucrose, food, sex and social interaction rapidly activate 5-HT neurons, but aversive stimuli including quinine and footshock do not. Both expected and unexpected rewards activate 5-HT neurons. After mice learn to wait for sucrose delivery, most 5-HT neurons fire tonically during waiting and then phasically on reward acquisition. Finally, GABA neurons are activated by aversive stimuli but inhibited when mice seek rewards. Thus, DRN 5-HT neurons positively encode a wide range of reward signals during anticipatory and consummatory phases of reward responses. Moreover, GABA neurons play a complementary role in reward processing. PMID- 26818708 TI - Swelling of ionic microgel particles in the presence of excluded-volume interactions: a density functional approach. AB - In this work a new density functional theory framework is developed to predict the salt-concentration dependent swelling state of charged microgels and the local concentration of monovalent ions inside and outside the microgel. For this purpose, elastic, solvent-induced and electrostatic contributions to the microgel free energy are considered together with the free energy of the ions. In addition to the electrostatic interaction, the model explicitly considers both the microgel-ion excluded-volume (steric) repulsion and the ionic correlations, in such a way that the formalism is consistent with the Hypernetted-Chain Closure approximation (HNC). We explore the role that the solvent quality, chain elasticity, salt concentration and microgel bare charge play on the swelling state, the effective charge and on the ionic density profiles. Our results show that the microgel-ion steric exclusion foments the increase of the particle size up to 10%. The role that the steric effect plays on the counterion distribution becomes more important when the microgel approaches the shrunken configuration, developing an accumulation peak at the microgel interface and a reduction in the inner core of the microgel that induce a significant increase of the microgel effective charge. We further find that deep inside the particle charge electroneutrality is achieved and a Donnan potential corrected by the steric exclusion is established. PMID- 26818707 TI - Topical imiquimod yields systemic effects due to unintended oral uptake. AB - Repetitive application of topical imiquimod is used as an experimental model for the induction of psoriasiform skin lesions in mice. The model is characterized by several inflammatory processes, including cytokine production both locally and systemically, cellular infiltration, and splenomegaly. To investigate the production of type I interferons in response to imiquimod-containing Aldara cream, IFNbeta-luciferase reporter mice were imaged in vivo and ex vivo. Type I interferons were found to be produced in the skin, but also in the intestinal system caused by unintended ingestion of imiquimod by the mice. Through the use of Elizabethan collars to prevent ingestion, these effects, including psoriasiform lesions were nearly completely prevented. Our findings reveal that topical treatment with Aldara induces a psoriasiform skin inflammation, but that its mode of action depends on ingestion of the chemical, which leads to systemic responses and affects local inflammation. Therefore, potential ingestion of topical treatments during experimental procedures should be taken into account during assessment of cutaneous inflammatory parameters in skin disease models. PMID- 26818709 TI - Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-mercaptobenzothiazole part II: Zebrafish. AB - Disruption of the thyroid hormone (TH) system, an important mode of action, can lead to ecologically relevant adverse outcomes, especially during embryonic development. The present study characterizes the effects of disruption of TH synthesis on swim bladder inflation during zebrafish early-life stages using 2 mercaptobenzothiazole (MBT), a thyroid peroxidase (TPO) inhibitor. Zebrafish were exposed to different MBT concentrations until 120/168h post fertilization (hpf) and 32days post fertilization (dpf), in two sets of experiments, to investigate the effects of TPO inhibition on posterior and anterior swim bladder inflation respectively, as well as whole body thyroid hormone concentrations (triiodothyronine (T3) and its prohormone, thyroxine (T4)). At 120hpf, MBT did not directly impair posterior chamber inflation or size, while anterior chamber inflation and size was impaired at 32dpf. As previously shown in amphibians and mammals, we confirmed that MBT inhibits TPO in fish. Whole-body T4 decreased after MBT exposure at both time points, while T3 levels were unaltered. There was a significant relationship between T4 levels and the anterior chamber surface at 32dpf. The absence of effects on posterior chamber inflation can possibly be explained by maternal transfer of T4 into the eggs. These maternally derived THs are depleted at 32dpf and cannot offset TPO inhibition, resulting in impaired anterior chamber inflation. Therefore, we hypothesize that TPO inhibition only inhibits swim bladder inflation during late development, after depletion of maternally derived T4. In a previous study, we showed that iodothyronine deiodinase (ID) knockdown impaired posterior chamber inflation during early development. Our findings, in parallel with similar effects observed in fathead minnow (see part I, this issue) suggest that thyroid disruption impacts swim bladder inflation, and imply an important distinction among specific subtypes of TH disrupting chemicals. However, the existence of another - yet unknown - mode of action of MBT impacting swim bladder inflation cannot be excluded. These results can be helpful for delineating adverse outcome pathways (AOPs) linking TPO inhibition, ID inhibition and other TH related molecular initiating events, to impaired swim bladder inflation in fish during early life stages. Such AOPs can support the use of in vitro enzyme inhibition assays for predicting reduced survival due to impaired posterior and anterior chamber inflation. PMID- 26818710 TI - Ultrafast strong-field photoelectron emission from biased metal surfaces: exact solution to time-dependent Schrodinger Equation. AB - Laser-driven ultrafast electron emission offers the possibility of manipulation and control of coherent electron motion in ultrashort spatiotemporal scales. Here, an analytical solution is constructed for the highly nonlinear electron emission from a dc biased metal surface illuminated by a single frequency laser, by solving the time-dependent Schrodinger equation exactly. The solution is valid for arbitrary combinations of dc electric field, laser electric field, laser frequency, metal work function and Fermi level. Various emission mechanisms, such as multiphoton absorption or emission, optical or dc field emission, are all included in this single formulation. The transition between different emission processes is analyzed in detail. The time-dependent emission current reveals that intense current modulation may be possible even with a low intensity laser, by merely increasing the applied dc bias. The results provide insights into the electron pulse generation and manipulation for many novel applications based on ultrafast laser-induced electron emission. PMID- 26818711 TI - Alterations of the cytoskeleton in human cells in space proved by life-cell imaging. AB - Microgravity induces changes in the cytoskeleton. This might have an impact on cells and organs of humans in space. Unfortunately, studies of cytoskeletal changes in microgravity reported so far are obligatorily based on the analysis of fixed cells exposed to microgravity during a parabolic flight campaign (PFC). This study focuses on the development of a compact fluorescence microscope (FLUMIAS) for fast live-cell imaging under real microgravity. It demonstrates the application of the instrument for on-board analysis of cytoskeletal changes in FTC-133 cancer cells expressing the Lifeact-GFP marker protein for the visualization of F-actin during the 24(th) DLR PFC and TEXUS 52 rocket mission. Although vibration is an inevitable part of parabolic flight maneuvers, we successfully for the first time report life-cell cytoskeleton imaging during microgravity, and gene expression analysis after the 31(st) parabola showing a clear up-regulation of cytoskeletal genes. Notably, during the rocket flight the FLUMIAS microscope reveals significant alterations of the cytoskeleton related to microgravity. Our findings clearly demonstrate the applicability of the FLUMIAS microscope for life-cell imaging during microgravity, rendering it an important technological advance in live-cell imaging when dissecting protein localization. PMID- 26818713 TI - Temperature dependence of nanosecond laser pulse thresholds of melanosome and microsphere microcavitation. PMID- 26818712 TI - Haematuria on the Spanish Registry of Glomerulonephritis. AB - Recent studies suggest a pathogenic role for glomerular haematuria among renal function. However, there is no data on the prevalence of haematuria from a large renal biopsy registry. We analysed the prevalence of gross (GH) and microscopic (mH) haematuria in 19,895 patients that underwent native renal biopsies from the Spanish Registry of Glomerulonephritis. Haematuria's overall incidence was 63% (GH 8.6% and mH 55.1%), being more frequent in males (64.7% vs. 62.4%). GH was more prevalent in patients <18 years (21.3% vs. 7.7%). The commonest clinical presentation associated with GH was acute kidney injury (31.5%) and IgA Nephropathy (IgAN) (33.6%) was the most frequent histological finding. GH patients showed a significantly (p < 0.05) lower eGFR and proteinuria levels as compared with patients with mH and without haematuria. Moreover, mH was more prevalent in adults (56.3%). Nephrotic syndrome was the commonest clinical presentation in mH patients (32.2%) and IgAN (18.5%) the most frequent histological finding. In conclusion, haematuria, is a frequent urinalysis finding in patients underwent native renal biopsy. The most frequent histological finding in both GH and mH is IgAN. Whereas, GH is more frequent in young males with acute kidney injury, mH is commoner among adults with nephrotic syndrome. PMID- 26818714 TI - Terahertz spectroscopy of brain tissue from a mouse model of Alzheimer's disease. PMID- 26818715 TI - Detection of Critical Genes Associated with Overall Survival (OS) and Progression Free Survival (PFS) in Reconstructed Canine B-Cell Lymphoma Gene Regulatory Network (GRN). AB - Canine B-cell lymphoma GRN was reconstructed from gene expression data in the STRING and MiMI databases. Critical genes of networks were identified and correlations of critical genes with overall survival (OS) and progression-free survival (PFS) were evaluated. Significant changes were detected in the expressions of GLUL, CD44, CD79A, ARF3, FOS, BLOC1S1, FYN, GZMB, GALNT3, IFI44, CD3G, GNG2, ESRP1, and CCND1 in the STRING network and of PECAM1, GLUL, CD44, GDI1, E2F4, TLE1, CD79A, UCP2, CCND1, FYN, RHOQ, BIN1, and A2M in the MiMI network. Final survival analysis highlighted CCND1 and FOS as genes with significant correlations with OS and PFS. PMID- 26818716 TI - Post-Operative Hemorrhage After Liver Transplantation: Risk Factors and Long-Term Outcome. AB - BACKGROUND: Increasing scarcity of donated liver grafts clearly demonstrates the desperate need for ongoing outcome analysis to improve patient and graft survival after liver transplantation. Coagulation is often severely deteriorated in patients suffering from liver disease, thus leading to bleeding complications after liver transplantation. MATERIAL AND METHODS: We included 770 liver transplantations in this single-center retrospective analysis to identify independent risk factors for post-operative hemorrhage. The relevance of bleeding complications was assessed with special regards to coagulation-related variables. Multivariate regression analyses allowed weighing of different risk factors. RESULTS: Post-operative hemorrhage leading to revision surgery was observed in 19.9% (n=153 cases) of cases and was revealed as an independent risk factor for mortality (p=0.014; HR: 1.457; 95%-CI: 1.081-1.964). Risk-adjusted multivariate regression analysis compiling all pre- and intra-operative donor and recipient variables revealed that only the number of transfused packed red blood cells (p<0.001; OR: 1.072; 95%-CI: 1.036-1.110), hepatitis B virus-related liver disease (p=0.019; OR: 0.082; 95%-CI: 0.010-0.666), model of end-stage liver disease-era (p=0.020; OR: 1.016; 95%-CI: 1.002-1.029), partial thromboplastin time at transplantation (p=0.021; OR: 1.016; 95%-CI: 1.002-1.029), and donor intensive care unit stay in days (p=0.009; OR: 1.009; 95%-CI: 1.002-1.016) were significantly associated with the occurrence of post-operative hemorrhage. CONCLUSIONS: Post-operative hemorrhage relevantly contributed post-transplant mortality. Avoidance of excessive packed red blood cell use during transplantation and short donor-intensive care unit stay lead to a decreased rate of bleeding complications. Coagulations state at transplantation is also relevant for favorable outcome. PMID- 26818717 TI - Endosperm-based postzygotic hybridization barriers: developmental mechanisms and evolutionary drivers. AB - The endosperm is a nourishing tissue that serves to support embryo growth. Failure of endosperm development will ultimately cause embryo arrest and seed lethality, a phenomenon that is frequently observed upon hybridization of related plant species or species that differ in ploidy. Endosperm-based interspecies or interploidy hybridization barriers depend on the direction of the hybridization, causing nonreciprocal seed defects. This reveals that the parental genomes are not equivalent, implicating parent-of-origin specific genes generating this type of hybridization barrier. Recent work revealed that endosperm-based hybridization barriers are rapidly evolving. In this review, we discuss the developmental mechanisms causing hybrid seed lethality in angiosperms as well as the evolutionary forces establishing endosperm-based postzygotic hybridization barriers. PMID- 26818718 TI - Engineering the Rhizosphere. AB - All components of the rhizosphere can be engineered to promote plant health and growth, two features that strongly depend upon the interactions of living organisms with their environment. This review describes the progress in plant and microbial molecular genetics and ecology that has led to a wealth of potential applications. Recent efforts especially deal with the plant defense machinery that is instrumental in engineering plant resistance to biotic stresses. Another approach involves microbial population engineering rather than single strain engineering. More generally, the plants (and the associated microbes) are no longer seen as 'individual' but rather as a holobiont, in other words a unit of selection in evolution, a concept that holds great promise for future plant breeding programs. PMID- 26818719 TI - On the origin of high activity of hcp metals for ammonia synthesis. AB - Structure and activity of nanoparticles of hexagonal close-packed (hcp) metals are studied using first-principles calculations. Results show that, in contact with a nitrogen environment, high-index {134[combining macron]2} facets are formed on hcp metal nanoparticles. Nitrogen molecules dissociate easily at kink sites on these high-index facets (activation barriers of <0.2 eV). Analysis of the site blocking effect and adsorption energies on {134[combining macron]2} facets explains the order of activity of hcp metals for ammonia synthesis: Re < Os < Ru. Our results indicate that the high activity of hcp metals for ammonia synthesis is due to the N-induced formation of {134[combining macron]2} facets with high activity for the dissociation of nitrogen molecules. However, quite different behavior for adsorption of dissociated N atoms leads to distinctive activity of hcp metals. PMID- 26818722 TI - Structural characterization of sulfated arabinans extracted from Cladophora glomerata Kutzing and their macrophage activation. AB - Water-soluble sulfated heteropolysaccharides were extracted from Cladophora glomerata Kutzing and fractionated by ion-exchange chromatography, which yielded two subfractions, F1 and F2. The crude and fractionated polysaccharides (F1 and F2) mostly consisted of carbohydrates (62.8-74.5%) with various amounts of proteins (9.00-17.3%) and sulfates (16.5-23.5%), including different levels of arabinose (41.7-54.4%), galactose (13.5-39.0%), glucose (0.80-10.6%), xylose (6.84-13.4%), and rhamnose (0.20-2.83%). Based on the size exclusion chromatography (SEC) profiles, the crude and fractions mainly contained one peak with shoulders having molecular weight (Mw) ranges of 358-1,501 * 10(3). The F1 fraction stimulated RAW264.7 cells to produce considerable amounts of nitric oxide and cytokines compared to the crude and F2 fraction. The backbone of the most potent immunostimulating fraction (F1) was alpha-(1->4)-L-arabinopyranoside with galactose and xylose residues as branches at O-2 position, and sulfates mainly at O-2 position as well. PMID- 26818724 TI - Reply to Dr Alphs and colleagues. PMID- 26818723 TI - The impact of the new cooperative medical scheme on financial burden of tuberculosis patients: evidence from six counties in China. AB - BACKGROUND: Tuberculosis (TB) patients in China encounter heavy financial burdens throughout the course of their treatment and it is unclear how China's health insurance systems affect the alleviation of this burden under the integrated approach. This study aimed to measure reimbursement for TB services under the New Cooperative Medical Scheme (NCMS) in rural China and to evaluate changes in catastrophic health expenditure (CHE) caused by the reimbursement policies. METHODS: Reimbursement data were obtained from routine data systems for the NCMS in Yichang (YC) and Hanzhong (HZ). 1884 TB inpatients reimbursed by NCMS from 2010 to 2012 were included. Household surveys were conducted. A total of 494 TB patients under the NCMS were selected in this paper. 12 Focus Group Discussions (FGDs) were held. We measured the impact of the NCMS by counterfactual analysis, which analyzed the financial burden alleviation. Equity was assessed by Concentration Index (CI), and disaggregated by project sites. RESULTS: TB inpatients were reimbursed with an effective reimbursement rate of 57.3 %. Average out-of-pocket (OOP) payments for outpatient and inpatient services after diagnosis were 1413 yuan and 430 yuan, and 3572 yuan and 3013 yuan in YC and HZ, respectively. The reimbursement level for TB outpatient care after diagnosis was very low due to a limited outpatient quota. TB patients in HZ incurred higher effective reimbursement rates, but the incidence of CHE remained higher. The reduction of CHE incidence after the NCMS showed no difference statistically (P > 0.05). The severity of CHE was alleviated slightly. CIs after reimbursement were all below zero and their absolute values were higher than those before reimbursement. CONCLUSIONS: Low reimbursement for TB patients could lead to heavy financial burden. Poor TB patients incurred high rates of CHE. The NCMS was found to be a protective factor for CHE, but the impact was modest and the equity of CHE did not improve. The NCMS reimbursement policies should be improved in the future to include a more comprehensive coverage of care. Supplemental programs may be necessary to expand coverage for TB care. PMID- 26818725 TI - Computational prediction of CRISPR cassettes in gut metagenome samples from Chinese type-2 diabetic patients and healthy controls. AB - BACKGROUND: CRISPR has been becoming a hot topic as a powerful technique for genome editing for human and other higher organisms. The original CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats coupled with CRISPR associated proteins) is an important adaptive defence system for prokaryotes that provides resistance against invading elements such as viruses and plasmids. A CRISPR cassette contains short nucleotide sequences called spacers. These unique regions retain a history of the interactions between prokaryotes and their invaders in individual strains and ecosystems. One important ecosystem in the human body is the human gut, a rich habitat populated by a great diversity of microorganisms. Gut microbiomes are important for human physiology and health. Metagenome sequencing has been widely applied for studying the gut microbiomes. Most efforts in metagenome study has been focused on profiling taxa compositions and gene catalogues and identifying their associations with human health. Less attention has been paid to the analysis of the ecosystems of microbiomes themselves especially their CRISPR composition. RESULTS: We conducted a preliminary analysis of CRISPR sequences in a human gut metagenomic data set of Chinese individuals of type-2 diabetes patients and healthy controls. Applying an available CRISPR-identification algorithm, PILER-CR, we identified 3169 CRISPR cassettes in the data, from which we constructed a set of 1302 unique repeat sequences and 36,709 spacers. A more extensive analysis was made for the CRISPR repeats: these repeats were submitted to a more comprehensive clustering and classification using the web server tool CRISPRmap. All repeats were compared with known CRISPRs in the database CRISPRdb. A total of 784 repeats had matches in the database, and the remaining 518 repeats from our set are potentially novel ones. CONCLUSIONS: The computational analysis of CRISPR composition based contigs of metagenome sequencing data is feasible. It provides an efficient approach for finding potential novel CRISPR arrays and for analysing the ecosystem and history of human microbiomes. PMID- 26818727 TI - The Influence of Nitrogen Dioxide on Arrhythmias in Spain and Its Relationship with Atmospheric Circulation. AB - Epidemiological studies suggest that increased ambient NO2 concentrations are associated with cardiovascular disease. However, none of them have examined the association between ambient air pollution and cardiac arrhythmias in the general population in Spain. This paper assesses the short-term association between the aforementioned air pollutant and hospital admissions for arrhythmia in nine different regions of Spain during a 6-year period (2005-2010), and the possible season-specific effects of the compound on this pathology, by performing a time series analysis based on Poisson regression models. The results show statistically significant positive relationship increases between arrhythmia admissions and increments in NO2 concentration during the whole year, most notably in wintertime. Moreover, while trying to establish a threshold for NO2 concentration above which the incidence of arrhythmia episodes increases significantly, this study reveals that hospital admissions increased linearly in response to an increase in as we move to higher NO2 concentration levels. Finally, an analysis of NO2 concentrations and their relationship with atmospheric circulation is performed, showing higher values of NO2 under anticyclonic conditions during winter that could be used for implementing pollution level alert protocols depending on forecast circulation patterns. PMID- 26818728 TI - The prognosis of acute symptomatic seizures after ischaemic stroke. AB - OBJECTIVE: Acute symptomatic seizure (AS) after ischaemic stroke is defined as a seizure occurring <=7 days of the stroke. There remains a lack of information on the prognosis of AS after ischaemic stroke and how it should be treated. METHODS: We prospectively recruited patients after their incidents of ischaemic stroke from a population-based stroke registry. Stroke aetiology was defined according to Trial-of-ORG-10172 in acute-stroke treatment (TOAST). Patients were examined for any transient complete-occlusion with recanalisation (TCOR) and haemorrhagic transformation. The seizure outcomes were (1) acute clustering of seizures <=7 days, (2) seizure recurrence associated with stroke recurrence beyond the 7-day period and (3) unprovoked seizure (US) >7 days. RESULTS: 104 patients (mean age 65 years/55% female) with AS after ischaemic stroke were identified (mean follow up 6.17 years). Comparison of the group of patients with AS and those without seizures showed that patients with AS had significantly less large-vessel and small-vessel disease but more cardioembolisms (p<0.05) and a higher proportion of TCOR (p<0.01), multiple territory infarcts (p=0.007) and haemorrhagic transformations (p<0.01). Using Kaplan-Meier statistics, the risk of acute clustering of seizures <=7 days was 22%, with a statistical trend for TCOR as a predictive factor (p=0.06). The risk of seizure recurrence associated with worsening/recurrence of stroke beyond 7 days was 13.5% at 2 years, 16.4% at 4 years and 18% at 8 years. Presence of >2 cardiovascular risk factors (p<0.05) and status epilepticus (P<0.05) are predictive risk factors on Cox regression model. The risk of US was 19% at 2 years, 25% at 4 years and 28% at 8 years with epileptiform EEG as a predictive factor (p<0.05). CONCLUSIONS: Seizure recurrence following AS after ischaemic stroke may appear as acute clustering. Afterwards, seizures may occur as often with a recurrent stroke as without one within 4.2 years. We recommend the use of antiepileptic agents for up to 4 years if the underlying stroke aetiology cannot be fully treated. PMID- 26818726 TI - Liposomal Amphotericin B (AmBisome((r))): A Review of the Pharmacokinetics, Pharmacodynamics, Clinical Experience and Future Directions. AB - Liposomal amphotericin B (AmBisome((r)); LAmB) is a unique lipid formulation of amphotericin B. LAmB is a standard of care for a wide range of medically important opportunistic fungal pathogens. LAmB has a significantly improved toxicity profile compared with conventional amphotericin B deoxycholate (DAmB). Despite nearly 20 years of clinical use, the pharmacokinetics and pharmacodynamics of this agent, which differ considerably from DAmB, remain relatively poorly understood and underutilized in the clinical setting. The molecular pharmacology, preclinical and clinical pharmacokinetics, and clinical experience with LAmB for the most commonly encountered fungal pathogens are reviewed. In vitro, experimental animal models and human clinical trial data are summarized, and novel routes of administration and dosing schedules are discussed. LAmB is a formulation that results in reduced toxicity as compared with DAmB while retaining the antifungal effect of the active agent. Its long terminal half-life and retention in tissues suggest that single or intermittent dosing regimens are feasible, and these should be actively investigated in both preclinical models and in clinical trials. Significant gaps remain in knowledge of pharmacokinetics and pharmacodynamics in special populations such as neonates and children, pregnant women and obese patients. PMID- 26818730 TI - Task-specific dystonia: pathophysiology and management. AB - Task-specific dystonia is a form of isolated focal dystonia with the peculiarity of being displayed only during performance of a specific skilled motor task. This distinctive feature makes task-specific dystonia a particularly mysterious and fascinating neurological condition. In this review, we cover phenomenology and its increasingly broad-spectrum risk factors for the disease, critically review pathophysiological theories and evaluate current therapeutic options. We conclude by highlighting the unique features of task-specific dystonia within the wider concept of dystonia. We emphasise the central contribution of environmental risk factors, and propose a model by which these triggers may impact on the motor control of skilled movement. By viewing task-specific dystonia through this new lens which considers the disorder a modifiable disorder of motor control, we are optimistic that research will yield novel therapeutic avenues for this highly motivated group of patients. PMID- 26818729 TI - Genome-wide association study of sporadic brain arteriovenous malformations. AB - BACKGROUND: The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium. METHODS: The Caucasian discovery cohort included 515 BAVM cases and 1191 controls genotyped using Affymetrix genome-wide SNP arrays. Genotype data were imputed to 1000 Genomes Project data, and well-imputed SNPs (>0.01 minor allele frequency) were analysed for association with BAVM. 57 top BAVM-associated SNPs (51 SNPs with p<10(-05) or p<10(-04) in candidate pathway genes, and 6 candidate BAVM SNPs) were tested in a replication cohort including 608 BAVM cases and 744 controls. RESULTS: The estimated heritability of BAVM was 17.6% (SE 8.9%, age and sex-adjusted p=0.015). None of the SNPs were significantly associated with BAVM in the replication cohort after correction for multiple testing. 6 SNPs had a nominal p<0.1 in the replication cohort and map to introns in EGFEM1P, SP4 and CDKAL1 or near JAG1 and BNC2. Of the 6 candidate SNPs, 2 in ACVRL1 and MMP3 had a nominal p<0.05 in the replication cohort. CONCLUSIONS: We performed the first GWAS of sporadic BAVM in the largest BAVM cohort assembled to date. No GWAS SNPs were replicated, suggesting that common SNPs do not contribute strongly to BAVM susceptibility. However, heritability estimates suggest a modest but significant genetic contribution. PMID- 26818731 TI - A Specific Transcriptome Signature for Guard Cells from the C4 Plant Gynandropsis gynandra. AB - C4 photosynthesis represents an excellent example of convergent evolution that results in the optimization of both carbon and water usage by plants. In C4 plants, a carbon-concentrating mechanism divided between bundle sheath and mesophyll cells increases photosynthetic efficiency. Compared with C3 leaves, the carbon-concentrating mechanism of C4 plants allows photosynthetic operation at lower stomatal conductance, and as a consequence, transpiration is reduced. Here, we characterize transcriptomes from guard cells in C3 Tareneya hassleriana and C4 Gynandropsis gynandra belonging to the Cleomaceae. While approximately 60% of Gene Ontology terms previously associated with guard cells from the C3 model Arabidopsis (Arabidopsis thaliana) are conserved, there is much less overlap between patterns of individual gene expression. Most ion and CO2 signaling modules appear unchanged at the transcript level in guard cells from C3 and C4 species, but major variations in transcripts associated with carbon-related pathways known to influence stomatal behavior were detected. Genes associated with C4 photosynthesis were more highly expressed in guard cells of C4 compared with C3 leaves. Furthermore, we detected two major patterns of cell-specific C4 gene expression within the C4 leaf. In the first, genes previously associated with preferential expression in the bundle sheath showed continually decreasing expression from bundle sheath to mesophyll to guard cells. In the second, expression was maximal in the mesophyll compared with both guard cells and bundle sheath. These data imply that at least two gene regulatory networks act to coordinate gene expression across the bundle sheath, mesophyll, and guard cells in the C4 leaf. PMID- 26818732 TI - SEUSS Integrates Gibberellin Signaling with Transcriptional Inputs from the SHR SCR-SCL3 Module to Regulate Middle Cortex Formation in the Arabidopsis Root. AB - A decade of studies on middle cortex (MC) formation in the root endodermis of Arabidopsis (Arabidopsis thaliana) have revealed a complex regulatory network that is orchestrated by several GRAS family transcription factors, including SHORT-ROOT (SHR), SCARECROW (SCR), and SCARECROW-LIKE3 (SCL3). However, how their functions are regulated remains obscure. Here we show that mutations in the SEUSS (SEU) gene led to a higher frequency of MC formation. seu mutants had strongly reduced expression of SHR, SCR, and SCL3, suggesting that SEU positively regulates these genes. Our results further indicate that SEU physically associates with upstream regulatory sequences of SHR, SCR, and SCL3; and that SEU has distinct genetic interactions with these genes in the control of MC formation, with SCL3 being epistatic to SEU. Similar to SCL3, SEU was repressed by the phytohormone GA and induced by the GA biosynthesis inhibitor paclobutrazol, suggesting that SEU acts downstream of GA signaling to regulate MC formation. Consistently, we found that SEU mediates the regulation of SCL3 by GA signaling. Together, our study identifies SEU as a new critical player that integrates GA signaling with transcriptional inputs from the SHR-SCR-SCL3 module to regulate MC formation in the Arabidopsis root. PMID- 26818733 TI - PRECISE--pregabalin in addition to usual care: statistical analysis plan. AB - BACKGROUND: Sciatica is a severe, disabling condition that lacks high quality evidence for effective treatment strategies. This a priori statistical analysis plan describes the methodology of analysis for the PRECISE study. METHODS/DESIGN: PRECISE is a prospectively registered, double blind, randomised placebo controlled trial of pregabalin compared to placebo, in addition to usual care in patients with sciatica. The aim of this study is to determine the efficacy and cost-effectiveness of pregabalin in reducing leg pain intensity (primary outcome). Secondary outcomes include disability (key secondary), back pain intensity, quality of life, participants' perceived global effect, work absenteeism and health utilisation. Information about medication usage and tolerability are also collected. Outcomes are collected over one year (weeks 2, 4, 8, 12, 26 and 52). Double data entry will be conducted for primary and key secondary outcomes. Other outcomes will be checked using a risk-based approach. Analyses will be consistent with the intention-to-treat principle. Statistical tests will be two-tailed with a p value <0.05 considered significant. Group allocation will remain masked until analyses and interpretation are finalised. Repeated-measure linear mixed models will assess the effect of treatment (pregabalin versus placebo) on primary and secondary outcomes at all time points. Fixed effects will include group allocation, visit as a categorical variable and the interaction between group and visit. Covariates will include baseline leg pain and symptom duration, with an interaction term between baseline leg pain and visit. Pairwise differences between groups will be tested at weeks 8 and 52. The number of serious adverse events and adverse events will be reported, and the proportion of patients per group who have at least one event will be compared using Fisher's exact test. An economic evaluation will be conducted if there is a treatment effect on the primary outcome at week 8. A subgroup analysis will assess whether presenting features of neuropathic pain at baseline modify the treatment effect of leg pain at week 8. DISCUSSION: This statistical analysis plan provides detailed methodology for the analysis of the PRECISE study, which aims to deliver much needed evidence about effective and affordable management of sciatica. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12613000530729. Registered 13 May 2013). PMID- 26818735 TI - Erratum to: Transient Aortic Occlusion Augments Collateral Blood Flow and Reduces Mortality During Severe Ischemia Due to Proximal Middle Cerebral Artery Occlusion. PMID- 26818734 TI - Effect of antibiotics on gut microbiota, glucose metabolism and body weight regulation: a review of the literature. AB - Gut bacteria are involved in a number of host metabolic processes and have been implicated in the development of obesity and type 2 diabetes in humans. The use of antibiotics changes the composition of the gut microbiota and there is accumulating evidence from observational studies for an association between exposure to antibiotics and development of obesity and type 2 diabetes. In the present paper, we review human studies examining the effects of antibiotics on body weight regulation and glucose metabolism and discuss whether the observed findings may relate to alterations in the composition and function of the gut microbiota. PMID- 26818736 TI - Cross-protection induced by Japanese encephalitis vaccines against different genotypes of Dengue viruses in mice. AB - Dengue viruses (DENVs) and Japanese encephalitis virus (JEV) are closely related mosquito-borne flaviviruses that cause very high global disease burdens. Although cross-reactivity and cross-protection within flaviviruses have been demonstrated, the effect of JEV vaccination on susceptibility to DENV infection has not been well elucidated. In this study, we found that vaccination with the JEV inactivated vaccine (INV) and live attenuated vaccine (LAV) could induce cross immune responses and cross-protection against DENV1-4 in mice. Despite the theoretical risk of immune enhancement, no increased mortality was observed in our mouse model. Additionally, low but consistently detectable cross-neutralizing antibodies against DENV2 and DENV3 were also observed in the sera of JEV vaccine immunized human donors. The results suggested that both JEV-LAV and JEV-INV could elicit strong cross-immunity and protection against DENVs, indicating that inoculation with JEV vaccines may influence the distribution of DENVs in co circulated areas and that the cross-protection induced by JEV vaccines against DENVs might provide important information in terms of DENV prevention. PMID- 26818737 TI - Homozygosity mapping in albinism patients using a novel panel of 13 STR markers inside the nonsyndromic OCA genes: introducing 5 novel mutations. AB - Albinism is a heterogeneous genetic disorder of melanin synthesis that results in hypopigmented hair, skin and eyes. It is associated with decreased visual acuity, nystagmus, strabismus and photophobia. Six genes are known to be involved in nonsyndromic oculocutaneous albinism (OCA). In this study, we aimed to find the disease causing mutations in albinism patients using homozygosity mapping. Twenty three unrelated patients with nonsyndromic OCA or autosomal recessive ocular albinism were recruited in this study. All of the patients' parents had consanguineous marriage and all were screened for TYR mutations previously. At first, we performed homozygosity mapping using fluorescently labeled primers to amplify a novel panel of 13 STR markers inside the OCA genes and then the screened loci in each family were studied using PCR and cycle sequencing methods. We found five mutations including three mutations in OCA2, one mutation in SLC45A2 and one mutation in C10ORF11 genes, all of which were novel. In cases where the disease causing mutations are identical by descent due to a common ancestor, these STR markers can enable us to screen for the responsible genes. PMID- 26818739 TI - Bringing healthcare to the UK's abused domestic workers. PMID- 26818738 TI - De novo KCNH1 mutations in four patients with syndromic developmental delay, hypotonia and seizures. AB - The voltage-gated Kv10.1 potassium channel, also known as ether-a-go-go-related gene 1, encoded by KCNH1 (potassium voltage-gated channel, subfamily H (eag related), member 1) is predominantly expressed in the central nervous system. Recently, de novo missense KCNH1 mutations have been identified in six patients with Zimmermann-Laband syndrome and in four patients with Temple-Baraitser syndrome. These syndromes were historically considered distinct. Here we report three de novo missense KCNH1 mutations in four patients with syndromic developmental delay and epilepsy. Two novel KCNH1 mutations (p.R357Q and p.R357P), found in three patients, were located at the evolutionally highly conserved arginine in the channel voltage-sensor domain (S4). Another mutation (p.G496E) was found in the channel pore domain (S6) helix, which acts as a hinge in activation gating and mainly conducts non-inactivating outward potassium current. A previously reported p.G496R mutation was shown to produce no voltage dependent outward current in CHO cells, suggesting that p.G496E may also disrupt the proper function of the Kv channel pore. Our report confirms that KCNH1 mutations are associated with syndromic neurodevelopmental disorder, and also support the functional importance of the S4 domain. PMID- 26818741 TI - Presence of Minority Resistant Variants After Failure of a Tenofovir, Emtricitabine, and Rilpivirine Regimen. PMID- 26818740 TI - Brief Report: Effect of CMV and HIV Transcription on CD57 and PD-1 T-Cell Expression During Suppressive ART. AB - HIV-infected men who have sex with men are nearly universally coinfected with cytomegalovirus (CMV). In this study of 45 HIV-infected men who have sex with men virologically suppressed on ART, we found that presence of seminal CMV DNA shedding and higher levels of systemic cellular HIV RNA transcription were both independently associated with increased PD-1 expression on circulating CD4 T cells, but not with higher levels of senescent (CD57) T cells. In addition, greater HIV RNA transcription was associated with lower CD57 expression on CD8 T cells. Although causality cannot be inferred from this retrospective study, these results suggest that asymptomatic CMV replication and residual cellular HIV transcription may contribute to persistent immune dysregulation during suppressive ART. PMID- 26818742 TI - Confirmation of a Protein-Protein Interaction in the Pantothenate Biosynthetic Pathway by Using Sortase-Mediated Labelling. AB - High-throughput studies have been widely used to identify protein-protein interactions; however, few of these candidate interactions have been confirmed in vitro. We have used a combination of isothermal titration calorimetry and fluorescence anisotropy to screen candidate interactions within the pantothenate biosynthetic pathway. In particular, we observed no interaction between the next enzyme in the pathway, pantothenate synthetase (PS), and aspartate decarboxylase, but did observe an interaction between PS and the putative Nudix hydrolase, YfcD. Confirmation of the interaction by fluorescence anisotropy was dependent upon labelling an adventitiously formed glycine on the protein N-terminal affinity purification tag by using Sortase. Subsequent formation of the protein-protein complex led to apparent restriction of the dynamics of this tag, thus suggesting that this approach could be generally applied to a subset of other protein protein interaction complexes. PMID- 26818743 TI - Cell therapy for heart disease: Trial sequential analyses of two Cochrane reviews. AB - Meta-analyses of cell therapy trials for heart disease have yielded discrepant results. To resolve limitations associated with meta-analyses, such as imprecision and accumulation of random errors, we conducted trial sequential analysis (TSA). Randomized controlled trials that administered autologous bone marrow-derived cells to patients who suffered acute myocardial infarction (AMI) or heart failure (HF) were included. TSA has been applied to two clinical outcomes, all-cause mortality and hospitalization for HF, and to left ventricular ejection fraction (LVEF), as a surrogate of heart function. The results suggest that there is evidence of reduction of the risk of mortality and hospitalization in HF, but insufficient evidence to determine treatment effect in AMI. Moreover, the treatment does not improve LVEF by more than a mean difference of 4% when administered to either AMI or HF patients. The required number of participants to include in a meta-analysis to detect treatment effect was also estimated. PMID- 26818745 TI - Chevalier T, mueller M, mougiakakos D, et al. Analysis of dendritic cell subpopulations in follicular lymphoma with respect to the tumor immune microenvironment. Leuk lymphoma. 2016. [epub ahead of print]. DOI: 10.3109/10428194.2015.1135432. PMID- 26818744 TI - Lead exposure increases blood pressure by increasing angiotensinogen expression. AB - Lead exposure can induce increased blood pressure. Several mechanisms have been proposed to explain lead-induced hypertension. Changes in angiotensinogen (AGT) expression levels or gene variants may also influence blood pressure. In this study, we hypothesized that AGT expression levels or gene variants contribute to lead-induced hypertension. A preliminary HEK293 cell model experiment was performed to analyze the association between AGT expression and lead exposure. In a population-based study, serum AGT level was measured in both lead-exposed and control populations. To further detect the influence of AGT gene single nucleotide polymorphisms (SNPs) in lead-induced hypertension, two SNPs (rs699 and rs4762) were genotyped in a case-control study including 219 lead-exposed subjects and 393 controls. Lead exposure caused an increase in AGT expression level in HEK 293 cell models (P < 0.001) compared to lead-free cells, and individuals exposed to lead had higher systolic and diastolic blood pressure (P < 0.001). Lead-exposed individuals had higher serum AGT levels compared to controls (P < 0.001). However, no association was found between AGT gene SNPs (rs699 and rs4762) and lead exposure. Nevertheless, the change in AGT expression level may play an important role in the development of lead-induced hypertension. PMID- 26818746 TI - Planar plasmonic chiral nanostructures. AB - A strong chiral optical response induced at a plasmonic Fano resonance in a planar Au heptamer nanostructure was experimentally and theoretically demonstrated. The scattering spectra show the characteristic narrow-band feature of Fano resonances for both left and right circular polarized lights, with a chiral response reaching 30% at the Fano resonance. Specifically, we systematically investigate the chiral response of planar heptamers with gradually changing the inter-particle rotation angles and separation distance. The chiral spectral characteristics clearly depend on the strength of Fano resonances and the associated near-field optical distributions. Finite element method simulations together with a multipole expansion method demonstrate that the enhanced chirality is caused by the excitation of magnetic quadrupolar and electric toroidal dipolar modes. Our work provides an effective method for the design of 2D nanostructures with a strong chiral response. PMID- 26818747 TI - Prevalence and influence factors of vitamin A deficiency of Chinese pregnant women. AB - BACKGROUND: Vitamin A plays an important role in the periods of rapid cellular growth and differentiation, especially during pregnancy, which is supplied by the mother to the fetus. The aim of this study is to assess the prevalence and potential influence factors of prenatal VAD of Chinese pregnant women. METHODS: China National Nutrition and Health Survey 2010-2013(CHNNS2010-2013) is a nationally representative cross-sectional study. It involved the random selection of 150 districts (urban) or counties (rural). Each site randomly selected 30 pregnant women. Because volume of blood and incomplete data was taken into consideration,the final sample was formed by 1209 participants. Serum retinol concentrations were measured by high performance liquid chromatography. Characteristics of the pregnant women were collected by a questionnaire. Comparing retinol level across categories of independent variables was tested by the Mann-Whitney U test. Logistic and linear regression analyses were used to identify influence factors of Chinese pregnant women. RESULTS: The mean serum retinol level of the pregnant women was 1.63 MUmol/L (95 % CI 1.60-1.67) and 64[5.3 % (95 % CI 4.03-6.56)] had VAD. The odds of VAD were significantly higher among the pregnant women in the poor rural areas and without college or university education and low- income. Pregnant women in the second and third trimester had 2.40 (95 % CI 1.05-5.46) and 2.82 (95 % CI 1.34-5.93) times increased odds of VAD compared with those in the first trimester respectively. Pregnant women of drinker had 3.10(1.65-5.81) times increased odds of VAD compared with those no drinker. Pregnant smokers had 5.68 (95 % CI 2.23-14.49) times higher odds of VAD compared with pregnant with non-smoker without passive smoking. CONCLUSIONS: VAD is of mild public-health issue in Chinese pregnant women. Such as : in the poor rural areas and without received college or university education and low- income and advanced gestational age and unhealthy lifestyles of pregnant women such as smoking and drinking. These were pertinent influence factors of VAD. PMID- 26818749 TI - Inappropriate Antibiotic Use and Gastric Acid Suppression Preceding Clostridium difficile Infection. PMID- 26818750 TI - Quality, safety and sustained therapeutic efficacy of blood-derived serum eye drops to treat dry eye syndrome: R&D road map for future progress. PMID- 26818748 TI - Potential Therapeutic Benefits of Maintaining Mitochondrial Health in Peripheral Neuropathies. AB - BACKGROUND: Peripheral neuropathies are a group of diseases characterized by malfunctioning of peripheral nervous system. Neuropathic pain, one of the core manifestations of peripheral neuropathy remains as the most severe disabling condition affecting the social and daily routine life of patients suffering from peripheral neuropathy. METHOD: The current review is aimed at unfolding the possible role of mitochondrial dysfunction in peripheral nerve damage and to discuss on the probable therapeutic strategies against neuronal mitotoxicity. The article also highlights the therapeutic significance of maintaining a healthy mitochondrial environment in neuronal cells via pharmacological management in context of peripheral neuropathies. RESULTS: Aberrant cellular signaling coupled with changes in neurotransmission, peripheral and central sensitization are found to be responsible for the pathogenesis of variant toxic neuropathies. Current research reports have indicated the possible involvement of mitochondria mediated redox imbalance as one of the principal causes of neuropathy aetiologies. In addition to imbalance in redox homeostasis, mitochondrial dysfunction is also responsible for alterations in physiological bioenergetic metabolism, apoptosis and autophagy pathways. CONCLUSIONS: In spite of various etiological factors, mitochondrial dysfunction has been found to be a major pathomechanism underlying the neuronal dysfunction associated with peripheral neuropathies. Pharmacological modulation of mitochondria either directly or indirectly is expected to yield therapeutic relief from various primary and secondary mitochondrial diseases. PMID- 26818752 TI - Preface the 2nd Wakayama symposium: current concepts in ocular cell biology. PMID- 26818751 TI - Structural and functional annotation of the MADS-box transcription factor family in grapevine. AB - BACKGROUND: MADS-box genes encode transcription factors that are involved in developmental control and signal transduction in eukaryotes. In plants, they are associated to numerous development processes most notably those related to reproductive development: flowering induction, specification of inflorescence and flower meristems, establishment of flower organ identity, as well as regulation of fruit, seed and embryo development. Genomic analyses of MADS-box genes in different plant species are providing new relevant information on the function and evolution of this transcriptional factor family. We have performed a true genome-wide analysis of the complete set of MADS-box genes in grapevine (Vitis vinifera), analyzed their expression pattern and establish their phylogenetic relationships (including MIKC* and type I MADS-box) with genes from 16 other plant species. This study was integrated to previous works on the family in grapevine. RESULTS: A total of 90 MADS-box genes were detected in the grapevine reference genome by completing current gene annotations with a genome-wide analysis based on sequence similarity. We performed a thorough in-depth curation of all gene models and combined the results with gene expression information including RNAseq data to clarifying the expression of newly identified genes and improve their functional characterization. Curated data were uploaded to the ORCAE database for grapevine in the frame of the grapevine genome curation effort. This approach resulted in the identification of 30 additional MADS box genes. Among them, ten new MIKC(C) genes were identified, including a potential new group of short proteins similar to the SVP protein subfamily. The MIKC* subgroup contains six genes in grapevine that can be grouped in the S (4 genes) and P (2 genes) clades, showing less redundancy than that observed in Arabidopsis thaliana. Expression pattern of these genes in grapevine is compatible with a role in male gametophyte development. Most of the identified new genes belong to the type I MADS-box genes and were classified as members of the Malpha and Mgamma subclasses. Ours analyses indicate that only few members of type I genes in grapevine have homology in other species and that species-specific clades appeared both in the Malpha and Mgamma subclasses. On the other hand, as deduced from the phylogenetic analysis with other plant species, genes that can be crucial for development of central cell, endosperm and embryos seems to be conserved in plants. CONCLUSIONS: The genome analysis of MADS-box genes in grapevine, the characterization of their pattern of expression and the phylogenetic analysis with other plant species allowed the identification of new MADS-box genes not yet described in other plant species as well as basic characterization of their possible role, particularly in the case of type I and MIKC* genes. PMID- 26818753 TI - Locating rearrangement events in a phylogeny based on highly fragmented assemblies. AB - BACKGROUND: The inference of genome rearrangement operations requires complete genome assemblies as input data, since a rearrangement can involve an arbitrarily large proportion of one or more chromosomes. Most genome sequence projects, especially those on non-model organisms for which no physical map exists, produce very fragmented assembles, so that a rearranged fragment may be impossible to identify because its two endpoints are on different scaffolds. However, breakpoints are easily identified, as long as they do not coincide with scaffold ends. For the phylogenetic context, in comparing a fragmented assembly with a number of complete assemblies, certain combinatorial constraints on breakpoints can be derived. We ask to what extent we can use breakpoint data between a fragmented genome and a number of complete genomes to recover all the arrangements in a phylogeny. RESULTS: We simulate genomic evolution via chromosomal inversion, fragmenting one of the genomes into a large number of scaffolds to represent the incompleteness of assembly. We identify all the breakpoints between this genome and the remainder. We devise an algorithm which takes these breakpoints into account in trying to determine on which branch of the phylogeny a rearrangement event occurred. We present an analysis of the dependence of recovery rates on scaffold size and rearrangement rate, and show that the true tree, the one on which the rearrangement simulation was performed, tends to be most parsimonious in estimating the number of true events inferred. CONCLUSIONS: It is somewhat surprising that the breakpoints identified just between the fragmented genome and each of the others suffice to recover most of the rearrangements produced by the simulations. This holds even in parts of the phylogeny disjoint from the lineage of the fragmented genome. PMID- 26818755 TI - Erratum to: Association of environmental chemicals & estrogen metabolites in children. PMID- 26818754 TI - Barriers to mental health service utilisation in Sudan - perspectives of carers and psychiatrists. AB - BACKGROUND: In order to scale up mental health care nationally, barriers to health services utilisation need to be identified and addressed. AIM: The aim of this study was to identify barriers to mental health services utilization in Sudan from the perspectives of carer's of mentally ill patients and psychiatrists and to make recommendations to address the identified barriers. METHODS: Mixed research methods were used in this cross sectional survey. The quantitative part was conducted with carers of mentally ill patients who were staying in Tijani Elmahi psychiatric hospital in Sudan, and the qualitative part was conducted with the psychiatric consultants in the country. RESULTS: 103 carers and six psychiatric consultants participated in the study. According to carers, the main barriers to utilisation of mental health services includes: the beliefs around mental illness, resorting to alternative treatments such as religious and traditional healers, centralization of mental health services, inadequate number of mental health staff, and mental health not being a priority by policy makers. In addition to these barriers, the psychiatric consultants identified stigma, cost of medications, and worries about medication's side effects as barriers to the utilisation of mental health services. The carers and psychiatrists proposed several solutions to address the barriers to health services utilisation. CONCLUSION: Carers and psychiatrists are aware of the barriers to mental health services utilisation in Sudan. Addressing these barriers require a health policy and political response. PMID- 26818756 TI - Muscle focal vibration in healthy subjects: evaluation of the effects on upper limb motor performance measured using a robotic device. AB - PURPOSE: Muscle vibration is a technique that applies a low-amplitude/high frequency vibratory stimulus to a specific muscle using a mechanical device. The aim of this study was to evaluate, using robot-based outcomes, the effects of focal muscle vibration, at different frequencies, on the motor performance of the upper limb in healthy subjects. METHODS: Forty-eight volunteer healthy subjects (age: 31 +/- 8 years) were enrolled. Subjects were assigned to three different groups: the first group, in which subjects underwent muscle vibration treatment with a frequency of 100 Hz; the second group of subjects underwent the same treatment protocol, but using a frequency of vibration of 200 Hz; finally, the control group did not undergo any treatment. The robot-based evaluation session consisted of visually guided reaching task, performed in the sagittal plane. RESULTS: Our results showed that the vibration treatment improved upper limb motor performance of healthy subjects from the baseline (T0) to 10 days after the end of the treatment (T2), but only the group treated with a frequency of 200 Hz reached statistical significance. Specifically, in this group we found an increase of the number of repetitions (T0: 51.4 +/- 22.7; T2: 66.3 +/- 11.8), and the smoothness of the movement, as showed by a decrease of the Normalized Jerk (T0: 10.5 +/- 2.8; T2: 7.7 +/- 0.5). CONCLUSION: The results of our study support the use of focal muscle vibration protocols in healthy subjects, to improve motor performance. PMID- 26818757 TI - Erratum to: Current and Novel Aspects on the Non-lysosomal beta Glucosylceramidase GBA2. PMID- 26818758 TI - Brain cortex mitochondrial bioenergetics in synaptosomes and non-synaptic mitochondria during aging. AB - Alterations in mitochondrial bioenergetics have been associated with brain aging. In order to evaluate the susceptibility of brain cortex synaptosomes and non synaptic mitochondria to aging-dependent dysfunction, male Swiss mice of 3 or 17 months old were used. Mitochondrial function was evaluated by oxygen consumption, mitochondrial membrane potential and respiratory complexes activity, together with UCP-2 protein expression. Basal respiration and respiration driving proton leak were decreased by 26 and 33 % in synaptosomes from 17-months old mice, but spare respiratory capacity was not modified by aging. Succinate supported state 3 respiratory rate was decreased by 45 % in brain cortex non-synaptic mitochondria from 17-month-old mice, as compared with young animals, but respiratory control was not affected. Synaptosomal mitochondria would be susceptible to undergo calcium-induced depolarization in 17 months-old mice, while non-synaptic mitochondria would not be affected by calcium overload. UCP-2 was significantly up-regulated in both synaptosomal and submitochondrial membranes from 17-months old mice, compared to young animals. UCP-2 upregulation seems to be a possible mechanism by which mitochondria would be resistant to suffer oxidative damage during aging. PMID- 26818760 TI - PredRSA: a gradient boosted regression trees approach for predicting protein solvent accessibility. AB - BACKGROUND: Protein solvent accessibility prediction is a pivotal intermediate step towards modeling protein tertiary structures directly from one-dimensional sequences. It also plays an important part in identifying protein folds and domains. Although some methods have been presented to the protein solvent accessibility prediction in recent years, the performance is far from satisfactory. In this work, we propose PredRSA, a computational method that can accurately predict relative solvent accessible surface area (RSA) of residues by exploring various local and global sequence features which have been observed to be associated with solvent accessibility. Based on these features, a novel and efficient approach, Gradient Boosted Regression Trees (GBRT), is first adopted to predict RSA. RESULTS: Experimental results obtained from 5-fold cross-validation based on the Manesh-215 dataset show that the mean absolute error (MAE) and the Pearson correlation coefficient (PCC) of PredRSA are 9.0 % and 0.75, respectively, which are better than that of the existing methods. Moreover, we evaluate the performance of PredRSA using an independent test set of 68 proteins. Compared with the state-of-the-art approaches (SPINE-X and ASAquick), PredRSA achieves a significant improvement on the prediction quality. CONCLUSIONS: Our experimental results show that the Gradient Boosted Regression Trees algorithm and the novel feature combination are quite effective in relative solvent accessibility prediction. The proposed PredRSA method could be useful in assisting the prediction of protein structures by applying the predicted RSA as useful restraints. PMID- 26818759 TI - Astrocyte Cultures Mimicking Brain Astrocytes in Gene Expression, Signaling, Metabolism and K+ Uptake and Showing Astrocytic Gene Expression Overlooked by Immunohistochemistry and In Situ Hybridization. AB - Based on differences in gene expression between cultured astrocytes and freshly isolated brain astrocytes it has been claimed that cultured astrocytes poorly reflect the characteristics of their in vivo counterparts. This paper shows that this is not the case with the cultures of mouse astrocytes we have used since 1978. The culture is prepared following guidelines provided by Drs. Monique Sensenbrenner and John Booher, with the difference that dibutyryl cyclic AMP is added to the culture medium from the beginning of the third week. This addition has only minor effects on glucose and glutamate metabolism, but it is crucial for effects by elevated K+ concentrations and for Ca2+ homeostasis, important aspects of astrocyte function. Work by Liang Peng and her colleagues has shown identity between not only gene expression but also drug-induced gene upregulations and editings in astrocytes cultured by this method and astrocytes freshly isolated from brains of drug-treated animals. Dr. Norenberg's laboratory has demonstrated identical upregulation of the cotransporter NKCC1 in ammonia-exposed astrocytes and rats with liver failure. Similarity between cultured and freshly isolated astrocytes has also been shown in metabolism, K+ uptake and several aspects of signaling. However, others have shown that the gene for the glutamate transporter GLT1 is not expressed, and rat cultures show some abnormalities in K+ effects. Nevertheless, the overall reliability of the cultured cells is important because immunohistochemistry and in situ hybridization poorly demonstrate many astrocytic genes, e.g., those of nucleoside transporters, and even microarray analysis of isolated cells can be misleading. PMID- 26818761 TI - Smad7 Knockdown Restores Aryl Hydrocarbon Receptor-mediated Protective Signals in the Gut. AB - BACKGROUND AND AIM: In Crohn's disease [CD], the pathological process is driven by an excessive immune response that is poorly counterbalanced by regulatory mechanisms. One such a mechanism involves aryl hydrocarbon receptor [AhR], a transcription factor that delivers protective signals in the gut. Expression of AhR is reduced in CD lamina propria mononuclear cells [LPMC] even though factors accounting for such a defect remain unknown. Since CD LPMC express elevated levels of Smad7, an inhibitor of transforming growth factor beta 1 [TGF-beta1] activity, and TGF-beta1 regulates AhR in other systems, we examined the link between AhR and Smad7 in the gut. METHODS: AhR and interleukin [IL]-22 were evaluated in normal LPMC stimulated with TGF-beta1 and 6-formylindolo[3,2 b]carbazole [Ficz], an activator of AhR, and in CD LPMC incubated with a Smad7 antisense oligonucleotide and then stimulated with Ficz and TGF-beta1. AhR and IL 22 expression was evaluated in LPMC of Smad7-transgenic mice. Finally, we evaluated the protective effect of Ficz on colitis in RAG1 mice injected with naive or Smad7-overexpressing T cells. RESULTS: In normal LPMC, TGF-beta1 induced AhR and this event was associated with increased production of IL-22 following stimulation with Ficz. Treatment of CD LPMC with Smad7 antisense oligonucleotide enabled TGF-beta1 to enhance AhR expression. Consistently, AhR expression and Ficz-induced IL-22 production were markedly reduced in T cells of Smad7 transgenic mice. In RAG1 mice, Ficz ameliorated colitis induced by wild type T cells but did not affect colitis induced by transfer of Smad7-overexpressing T cells. CONCLUSIONS: The inverse correlation between Smad7 and AhR expression helps to propagate inflammatory signals in the gut. PMID- 26818762 TI - Prevalence and Natural History of Microscopic Colitis: A Population-Based Study With Long-term Clinical Follow-up in Terrassa, Spain. AB - BACKGROUND AND AIMS: Few studies have assessed the prevalence of microscopic colitis (MC) and the natural history of this disease is not well known. The aim of this study was to evaluate the prevalence rate of MC, the burden of disease in terms of loss of health and the long-term natural history of MC in a population based cohort study. METHODS: Cases were obtained from the pathology department registry Hospital Universitari Mutua Terrassa. Belonging to the catchment area, maintaining residence in that area, and being alive on August 31, 2014 were confirmed for each case. Adjusted prevalence rates were calculated. Current active drugs for MC and diarrhoea persistence in every patient were recorded. RESULTS: The prevalence rate of MC was 107 per 10(5) inhabitants. The rate of patients with active disease, i.e. those representing the true burden of the disease in terms of loss of health, was 31 per 10(5) inhabitants. After a follow up of 7.8+/-0.38 years from diagnosis, 75% of the patients experienced prolonged disease remission, defined as clinical remission without requiring drugs for 1 year or more. The only variable associated with prolonged MC remission was how clinical remission was achieved (spontaneous 93.3%, drug-induced, 60.5%; odds ratio 8.4, 95% confidence interval 2.7-26). CONCLUSIONS: The rate of patients with MC and active disease, which represents the true disease burden in terms of loss of health, is low. Most patients with MC experience prolonged disease remission, with key differences between spontaneous and drug-induced clinical remission. PMID- 26818763 TI - Obesity inhibits the osteogenic differentiation of human adipose-derived stem cells. AB - BACKGROUND: Craniomaxillofacial defects secondary to trauma, tumor resection, or congenital malformations are frequent unmet challenges, due to suboptimal alloplastic options and limited autologous tissues such as bone. Significant advances have been made in the application of adipose-derived stem/stromal cells (ASCs) in the pre-clinical and clinical settings as a cell source for tissue engineering approaches. To fully realize the translational potential of ASCs, the identification of optimal donors for ASCs will ensure the successful implementation of these cells for tissue engineering approaches. In the current study, the impact of obesity on the osteogenic differentiation of ASCs was investigated. METHODS: ASCs isolated from lean donors (body mass index <25; lnASCs) and obese donors (body mass index >30; obASCs) were induced with osteogenic differentiation medium as monolayers in an estrogen-depleted culture system and on three-dimensional scaffolds. Critical size calvarial defects were generated in male nude mice and treated with scaffolds implanted with lnASCs or obASCs. RESULTS: lnASCs demonstrated enhanced osteogenic differentiation in monolayer culture system, on three-dimensional scaffolds, and for the treatment of calvarial defects, whereas obASCs were unable to induce similar levels of osteogenic differentiation in vitro and in vivo. Gene expression analysis of lnASCs and obASCs during osteogenic differentiation demonstrated higher levels of osteogenic genes in lnASCs compared to obASCs. CONCLUSION: Collectively, these results indicate that obesity reduces the osteogenic differentiation capacity of ASCs such that they may have a limited suitability as a cell source for tissue engineering. PMID- 26818764 TI - Analysis of drug treatment outcome in clarithromycin-resistant Mycobacterium avium complex lung disease. AB - BACKGROUND: Although the isolation of clarithromycin (CAM)-resistant Mycobacterium avium complex (MAC) indicates a poor treatment outcome and increased mortality, there have been only a few reports on drug treatment for CAM resistant MAC lung disease. We aimed to reveal the effectiveness of the continuation of a macrolide and the use of a multidrug regimen in the treatment of CAM-resistant MAC lung disease. METHODS: Among patients with MAC pulmonary disease as defined by the 2007 criteria of the American Thoracic Society and the Infectious Diseases Society of America statement, those with CAM-resistant MAC (minimum inhibitory concentration >=32 MUg/ml) isolated, newly diagnosed and treated from January 2009 to June 2013 were analysed in this study. Effectiveness was measured based on culture conversion rate and improvement of radiological findings. RESULTS: Thirty-three HIV-negative patients were analysed in this study. Twenty-six were treated with a regimen containing CAM or azithromycin (AZM), and 21 patients were treated with three or more drugs except macrolide. The median duration to be evaluated was 10.4 months after beginning the treatment regimen. Sputum conversion (including cases of inability to expectorate sputum) was achieved in 12 (36%) patients. Radiological effectiveness improved in 4 (12%) patients, was unchanged in 11 (33%) patients and worsened in 18 (55%) patients. In the multivariate analysis, CRP <1.0 mg/dl (p = 0.017, odds ratio 12, 95% confidence interval (CI) 1.6-95) was found to be the only significant risk factor for radiological non-deterioration, and no significant risk factors for microbiological improvement were found. CONCLUSIONS: Our results suggested that continuation of macrolides or the addition of a new quinolone or injectable aminoglycoside to therapy with rifampicin and ethambutol would not improve clinical outcome after the emergence of CAM-resistant MAC. However, further prospective study is required to evaluate the precise clinical efficacy and effectiveness of these drugs. PMID- 26818765 TI - Systematic review and meta-analysis: sodium picosulfate/magnesium citrate vs. polyethylene glycol for colonoscopy preparation. AB - BACKGROUND AND AIMS: Previous studies comparing sodium picosulfate/magnesium citrate (SPMC) with polyethylene glycol (PEG) drew inconsistent conclusions. We conducted a meta-analysis to compare the performance of the two agents for colonoscopy preparation. METHODS: A search of randomized controlled trials (RCTs) up to July 2015 was acquired, using MEDLINE, EMBASE, the Cochrane Library, and Google Scholar. We calculated the pooled estimates of bowel cleanliness, polyp/adenoma detection rate (PDR/ADR), completion of preparation, willingness to repeat identical bowel preparation, and adverse events by using relative risk (RR) with random-effects models. A non-inferiority analysis was performed, comparing SPMC to PEG for bowel cleaning efficacy. RESULTS: A total of 25 RCTs were qualified for analysis. There was no statistically significant difference between the two agents in bowel cleanliness, but the effect direction showed a trend in favor of PEG (RR 0.93; 95 % CI 0.86-1.01, P = 0.07). The non-inferiority analysis demonstrated the non-inferiority of SPMC by retaining at least 90 % of the effect of PEG. Similarly, there was no significant difference between the two agents in PDR (RR 0.94; 95 % CI 0.82-1.08, P = 0.37) and ADR (RR 0.88; 95 % CI 0.74-1.05, P = 0.16). However, a higher proportion of patients were likely to complete SPMC preparation (RR 1.08; 95 % CI 1.04-1.13, P < 0.001) and were willing to repeat SPMC preparation (RR 1.44; 95 % CI 1.25-1.67, P < 0.001). The total number of adverse events was significantly lower in the SPMC group (RR 0.78; 95 % CI 0.66-0.93, P = 0.004). CONCLUSIONS: SPMC, with better tolerability and less frequent adverse events, demonstrated non-inferior bowel cleaning efficacy than that of the PEG. Large-scale, well-organized, head-to-head studies are warranted. PMID- 26818766 TI - Targeting oxidative stress to reduce osteoarthritis. AB - Osteoarthritis (OA) is the commonest chronic disease, with an estimated 9.6 % of men and 18.0 % of women aged over 60 years having symptomatic OA according to the World Health Organisation. Despite this prevalence, no therapies to slow disease progression are currently available. Oxidative stress has been described as an important factor in various diseases, and more recently in OA. Evidence for using antioxidants to reduce OA severity is slowly accumulating but further understanding of their chondroprotective mechanisms in joint tissues is still required to demonstrate potential benefit to patients. A new study implicates the transcriptional repressor Bach-1 and its downstream target HO-1 as important players in this process. PMID- 26818768 TI - 'Catastrophic' healthcare expenditure: critique of a problematic concept and a proposal. PMID- 26818767 TI - GTPase domain driven dimerization of SEPT7 is dispensable for the critical role of septins in fibroblast cytokinesis. AB - Septin 7 (SEPT7) has been described to be essential for successful completion of cytokinesis in mouse fibroblasts, and Sept7-deficiency in fibroblasts constitutively results in multinucleated cells which stop proliferation. Using Sept7(flox/flox)fibroblasts we generated a cellular system, where the cytokinetic defects of Cre-mediated deletion of the Sept7 gene can be rescued by ectopically expressed doxycycline-inducible wild type SEPT7. Using this system, we analyzed the ability of SEPT7-mutants with alterations in their GTPase domain-dependent dimerization to prevent multinucleation and rescue proliferation. Although biochemical analysis of the mutants demonstrates differences in homo- and/or hetero-polymerization, in GTP-binding and/or GTPase activities, all analyzed mutants were able to rescue the cytokinesis phenotype of Sept7(flox/flox)fibroblasts associated with Cre-mediated deletion of endogenous Sept7. These findings indicate that the ability of septins to assemble into well defined SEPT7-dimerization dependent native filaments is dispensable for cytokinesis in fibroblasts and opens the way to search for other mechanisms of the involvement of SEPT7 in cytokinesis. PMID- 26818769 TI - Pharmacomechanical thrombectomy: 2015 update. AB - Pharmacomechanical Thrombectomy (PMT) is recognized as a recent advancement in the treatment of lower extremity deep venous thrombosis (DVT). Evidence for the use of this modality is growing rapidly, primarily based on anecdotal experience and large case series. Currently, the majority of patients with lower extremity DVT are treated with anticoagulation or compressive therapy without adjunctive surgical or interventional procedures. This article reviews the current evidence supporting the use of PMT over catheter directed thrombolysis or simple anticoagulation and the expected benefits that can be realized from each modality. In addition the relevant unique characteristics to each device currently available are described focusing on mechanism of action and potential side effects. PMID- 26818771 TI - Sperm dispersal distances estimated by parentage analysis in a brooding scleractinian coral. AB - Within populations of brooding sessile corals, sperm dispersal constitutes the mechanism by which gametes interact and mating occurs, and forms the first link in the network of processes that determine specieswide connectivity patterns. However, almost nothing is known about sperm dispersal for any internally fertilizing coral. In this study, we conducted a parentage analysis on coral larvae collected from an area of mapped colonies, to measure the distance sperm disperses for the first time in a reef-building coral and estimated the mating system characteristics of a recently identified putative cryptic species within the Seriatopora hystrix complex (ShA; Warner et al. 2015). We defined consensus criteria among several replicated methods (COLONY 2.0, CERVUS 3.0, MLTR v3.2) to maximize accuracy in paternity assignments. Thirteen progeny arrays indicated that this putative species produces exclusively sexually derived, primarily outcrossed larvae (mean t(m) = 0.999) in multiple paternity broods (mean r(p) = 0.119). Self-fertilization was directly detected at low frequency for all broods combined (2.8%), but comprised 23% of matings in one brood. Although over 82% of mating occurred between colonies within 10 m of each other (mean sperm dispersal = 5.5 m +/- 4.37 SD), we found no evidence of inbreeding in the established population. Restricted dispersal of sperm compared to slightly greater larval dispersal appears to limit inbreeding among close relatives in this cryptic species. Our findings establish a good basis for further work on sperm dispersal in brooding corals and provide the first information about the mating system of a newly identified and abundant cryptic species. PMID- 26818770 TI - A mouse model for a partially inactive obesity-associated human MC3R variant. AB - We previously reported children homozygous for two MC3R sequence variants (C17A+G241A) have greater fat mass than controls. Here we show, using homozygous knock-in mouse models in which we replace murine Mc3r with wild-type human (MC3R(hWT/hWT)) and double-mutant (C17A+G241A) human (MC3R(hDM/hDM)) MC3R, that MC3R(hDM/hDM) have greater weight and fat mass, increased energy intake and feeding efficiency, but reduced length and fat-free mass compared with MC3R(hWT/hWT). MC3R(hDM/hDM) mice do not have increased adipose tissue inflammatory cell infiltration or greater expression of inflammatory markers despite their greater fat mass. Serum adiponectin levels are increased in MC3R(hDM/hDM) mice and MC3R(hDM/hDM) human subjects. MC3R(hDM/hDM) bone- and adipose tissue-derived mesenchymal stem cells (MSCs) differentiate into adipocytes that accumulate more triglyceride than MC3R(hWT/hWT) MSCs. MC3R(hDM/hDM) impacts nutrient partitioning to generate increased adipose tissue that appears metabolically healthy. These data confirm the importance of MC3R signalling in human metabolism and suggest a previously-unrecognized role for the MC3R in adipose tissue development. PMID- 26818772 TI - Assessing the daily stability of the cortisol awakening response in a controlled environment. AB - BACKGROUND: Levels of cortisol, the end product of the hypothalamic-pituitary adrenal (HPA) axis, display a sharp increase immediately upon awakening, known as the cortisol awakening response (CAR). The daily stability of the CAR is potentially influenced by a range of methodological factors, including light exposure, participant adherence, sleep duration and nocturnal awakenings, making inferences about variations in the CAR difficult. The aim of the present study was to determine the daily stability of multiple measurement indices of the CAR in a highly-controlled sleep laboratory environment. A secondary aim was to examine the association between objective sleep continuity and sleep architecture, and the CAR. METHODS: The CAR was assessed in 15 healthy normal sleepers (seven male, eight female, Mage = 23.67 +/- 3.49 years) on three consecutive weekday mornings. Sleep was measured objectively using polysomnography. Saliva samples were obtained at awakening, +15, +30, +45 and +60 min, from which multiple CAR measurement indices were derived: cortisol levels at each time point, awakening cortisol levels, the mean increase in cortisol levels (MnInc) and total cortisol secretion during the measurement period. Morning 2 and Morning 3 awakening cortisol levels, MnInc and total cortisol secretion were compared and the relationship between Night 1 and Night 2 objective measures of sleep continuity and architecture, and the subsequent CAR, was also assessed. RESULTS: There were no differences in cortisol levels at each time point, or total cortisol secretion during the CAR period, between Morning 2 and Morning 3. Awakening cortisol levels were lower, and the MnInc was higher, on Morning 3. Morning 2 and Morning 3 awakening levels (r = 0.77) and total cortisol secretion (r = 0.82), but not the magnitude of increase, were positively associated. CONCLUSIONS: The stability of the CAR profile and total cortisol secretion, but not awakening cortisol levels or the magnitude of increase, was demonstrated across two consecutive mornings of measurement in a highly-controlled environment. Awakening cortisol levels, and the magnitude of increase, may be sensitive to differences in daily activities. PMID- 26818773 TI - Subhaplogroup D4b1 enhances the risk of cervical cancer initiation: A case control study in southern China. AB - AIM: To investigate whether mitochondrial DNA (mtDNA) background (haplogroup) is associated with cervical cancer in patients in southern China. METHODS: A case control study of 150 patients with cervical cancer and 217 geographically matched controls was conducted in Wenzhou, a southern Chinese city in the Zhejiang province. DNA from peripheral blood was extracted and sequenced. Sequences were aligned to the mtDNA revised Cambridge Reference Sequence (GenBank number NC_012920) to determine mtDNA single nucleotide polymorphisms (SNPs) and haplogroups. RESULTS: We found that both M and N haplogroups and their diagnostic SNPs (A10398G and C10400T) are not associated with the risk of cervical cancer. However, individuals with haplogroup D4b1/D4b1*, an M subhaplogroup, exhibited an increased risk of cervical cancer (odds ratio [OR] = 1.034; 95% confidence interval [CI] 1.004, 1.066; P = 0.011/OR =1.027; 95% CI 1.001, 1.055; P = 0.027). Individuals with SNPs C10181T/A10136G (OR =1.034; 95% CI 1.004, 1.066; P = 0.011/OR =1.027; 95% CI 1.001, 1.055; P = 0.027) were more susceptible to cervical cancer than individuals without. Furthermore, we determined that mtDNA background is not associated with the progression of cervical cancer. CONCLUSIONS: Our results indicate that mtDNA haplogroups play a role in cervical cancer initiation. PMID- 26818774 TI - Extending the Acute Care Surgery Paradigm to Global Surgery. PMID- 26818775 TI - Acceptance of Commercially Available Wearable Activity Trackers Among Adults Aged Over 50 and With Chronic Illness: A Mixed-Methods Evaluation. AB - BACKGROUND: Physical inactivity and sedentary behavior increase the risk of chronic illness and death. The newest generation of "wearable" activity trackers offers potential as a multifaceted intervention to help people become more active. OBJECTIVE: To examine the usability and usefulness of wearable activity trackers for older adults living with chronic illness. METHODS: We recruited a purposive sample of 32 participants over the age of 50, who had been previously diagnosed with a chronic illness, including vascular disease, diabetes, arthritis, and osteoporosis. Participants were between 52 and 84 years of age (mean 64); among the study participants, 23 (72%) were women and the mean body mass index was 31 kg/m(2). Participants tested 5 trackers, including a simple pedometer (Sportline or Mio) followed by 4 wearable activity trackers (Fitbit Zip, Misfit Shine, Jawbone Up 24, and Withings Pulse) in random order. Selected devices represented the range of wearable products and features available on the Canadian market in 2014. Participants wore each device for at least 3 days and evaluated it using a questionnaire developed from the Technology Acceptance Model. We used focus groups to explore participant experiences and a thematic analysis approach to data collection and analysis. RESULTS: Our study resulted in 4 themes: (1) adoption within a comfort zone; (2) self-awareness and goal setting; (3) purposes of data tracking; and (4) future of wearable activity trackers as health care devices. Prior to enrolling, few participants were aware of wearable activity trackers. Most also had been asked by a physician to exercise more and cited this as a motivation for testing the devices. None of the participants planned to purchase the simple pedometer after the study, citing poor accuracy and data loss, whereas 73% (N=32) planned to purchase a wearable activity tracker. Preferences varied but 50% felt they would buy a Fitbit and 42% felt they would buy a Misfit, Jawbone, or Withings. The simple pedometer had a mean acceptance score of 56/95 compared with 63 for the Withings, 65 for the Misfit and Jawbone, and 68 for the Fitbit. To improve usability, older users may benefit from devices that have better compatibility with personal computers or less-expensive Android mobile phones and tablets, and have comprehensive paper based user manuals and apps that interpret user data. CONCLUSIONS: For older adults living with chronic illness, wearable activity trackers are perceived as useful and acceptable. New users may need support to both set up the device and learn how to interpret their data. PMID- 26818776 TI - VIP and CRF reduce ADAMTS expression and function in osteoarthritis synovial fibroblasts. AB - ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family is known to play an important role in the pathogenesis of osteoarthritis (OA), working on aggrecan degradation or altering the integrity of extracellular matrix (ECM). Thus, the main purpose of our study was to define the role of vasoactive intestinal peptide (VIP) and corticotrophin-releasing factor (CRF), as immunoregulatory neuropeptides, on ADAMTS production in synovial fibroblasts (SF) from OA patients and healthy donors (HD). OA- and HD-SF were stimulated with pro inflammatory mediators and treated with VIP or CRF. Both neuropeptides decreased ADAMTS-4, -5, -7 and -12 expressions, aggrecanase activity, glycosaminoglycans (GAG), and cartilage oligomeric matrix protein (COMP) degradation after stimulation with fibronectin fragments (Fn-fs) in OA-SF. After stimulation with interleukin-1beta, VIP reduced ADAMTS-4 and -5, and both neuropeptides decreased ADAMTS-7 production and COMP degradation. Moreover, VIP and CRF reduced Runx2 and beta-catenin activation in OA-SF. Our data suggest that the role of VIP and CRF on ADAMTS expression and cartilage degradation could be related to the OA pathology since scarce effects were produced in HD-SF. In addition, their effects might be greater when a degradation loop has been established, given that they were higher after stimulation with Fn-fs. Our results point to novel OA therapies based on the use of neuropeptides, since VIP and CRF are able to stop the first critical step, the loss of cartilage aggrecan and the ECM destabilization during joint degradation. PMID- 26818777 TI - A D-optimal design to model the performances of dressings and devices for negative pressure wound therapy. AB - A D-optimal design was used to identify and model variables that affect the transit time of wound exudate through an illustrative dressing used for negative pressure wound therapy. Many authors have addressed the clinical benefits of negative pressure wound therapy, but limited information is available on how to assess performances of dressings. In this paper, the transit time of wound exudate through a dressing was chosen as a model parameter to show how experimental design (DOE) can be used for this purpose. Results demonstrated that rate of exudate production, temperature and dressing thickness were the variables with the largest impact on transit time. The DOE approach could be used to model other dressing properties, like for example capability of absorbing excess exudate or breathability. PMID- 26818778 TI - Changes of HFRS Incidence Caused by Vaccine Intervention in Yichun City, China, 2005-2013. AB - BACKGROUND: Since 2009, the Hemorrhagic Fever with Renal Syndrome (HFRS) Targeted Expanded Program on Immunization (EPI) has been carried out in the 16-60 age population in Yichun City of Jiangxi Province. However, the annual reported incidences of HFRS in Yichun City Increased significantly from 2009 to 2013. MATERIAL/METHODS: The information on HFRS reported cases were obtained from the China Information System for Disease Control and Prevention (CISDCP), and demographic data was collected from the Basic Information System. Hantavirus specific antigen and antibody of rodent specimens were tested by enzyme-linked immunosorbent assay (ELISA) or immune fluorescent assay. RESULTS: The annual HFRS incidences among all age subgroups presented growth tendencies in non-EPI targeted regions and EPI targeted regions, except for the EPI target population. The annual incidences of EPI target population were stable at around 10 per 100,000 population from 2008 to 2013. HFRS annual incidence was significantly related to rat virus index among all age subgroups in non-EPI targeted regions and >60 age subgroup in EPI targeted regions. CONCLUSIONS: HFRS vaccine implement has had a notable effect in HFRS prevention and control. PMID- 26818779 TI - Effective treatment by glycolic acid peeling for cutaneous manifestation of familial generalized acanthosis nigricans caused by FGFR3 mutation. AB - BACKGROUND: Acanthosis nigricans (AN) can occur as a cutaneous manifestation of genetic diseases, one of which is associated with activating mutations of the fibroblast growth factor receptor 3 gene (FGFR3). OBJECTIVE: We explored familial AN patients with FGFR3 mutations and examined the effectiveness of glycolic acid (GA) peeling in improving their skin manifestations. METHODS: Sanger sequencing was performed for the genomic DNA extracted from leucocytes of the family members involving familial AN. GA peeling was carried out for the two patients of familial AN once every 2 weeks. RESULTS: Heterozygous c.1949A>C (p.K650T) mutation in FGFR3 was identified for the affected family members examined, whereas the wild-type sequence was found for two unaffected individuals. Hyperpigmentation and coarseness of the skin were improved by GA peeling at regular intervals with few adverse effects. CONCLUSION: We diagnosed our cases as familial generalized AN caused by heterozygous c.1949A>C (p.K650T) mutation of FGFR3. We propose that GA peeling is a useful and safe therapeutic option to treat familial AN. PMID- 26818780 TI - Molecular evolution of gas cavity in [NiFeSe] hydrogenases resurrected in silico. AB - Oxygen tolerance of selenium-containing [NiFeSe] hydrogenases (Hases) is attributable to the high reducing power of the selenocysteine residue, which sustains the bimetallic Ni-Fe catalytic center in the large subunit. Genes encoding [NiFeSe] Hases are inherited by few sulphate-reducing delta proteobacteria globally distributed under various anoxic conditions. Ancestral sequences of [NiFeSe] Hases were elucidated and their three-dimensional structures were recreated in silico using homology modelling and molecular dynamic simulation, which suggested that deep gas channels gradually developed in [NiFeSe] Hases under absolute anaerobic conditions, whereas the enzyme remained as a sealed edifice under environmental conditions of a higher oxygen exposure risk. The development of a gas cavity appears to be driven by non-synonymous mutations, which cause subtle conformational changes locally and distantly, even including highly conserved sequence regions. PMID- 26818781 TI - D-dimer and factor VIIa in atrial fibrillation - prognostic values for cardiovascular events and effects of anticoagulation therapy. A RE-LY substudy. AB - Coagulation markers may improve monitoring the risk of stroke and bleeding in patients with atrial fibrillation (AF) during anticoagulant treatment. We examined baseline levels of D-dimer and their association with stroke, cardiovascular death and major bleeding in 6,202 AF patients randomised to dabigatran or warfarin in the RE-LY trial. The effects of treatment on serial levels of D-dimer and coagulation factor (F) VIIa in 2,567 patients were also analysed. Baseline D-dimer levels were related to the rate of stroke/systemic embolism (SEE) with 0.64 % in the lowest quartile (Q1, as reference) (D-dimer < 298 ug/l), 1.38 % Q2 (D-dimer 298-473 ug/l), 1.71 % Q3 (D-dimer 474-822 ug/l) and 2.00 % in Q4 (D-dimer > 822 ug/l) (p=0.0007). Similar associations were shown for cardiovascular death and major bleeding. Addition of baseline D-dimer to established clinical risk factors improved prediction of stroke/SEE, cardiovascular death and major bleeding (C-index increased from 0.66 to 0.68, 0.71 to 0.73 and 0.66 to 0.67, respectively). Dabigatran provided a greater reduction of D-dimer levels than warfarin regardless of baseline anticoagulant treatment. On-treatment levels of FVIIa were markedly reduced by warfarin (median 12.1-13.8 mU/ml) but significantly higher with dabigatran (median 39.4-49.0 mU/ml) at all-time points. Dabigatran is associated with greater reduction in D dimer without the pronounced reduction of FVIIa seen with warfarin. These different effects on the coagulation system might explain the better efficacy and less intracranial bleeding observed with dabigatran compared with warfarin. PMID- 26818782 TI - Characterizing the optimal flux space of genome-scale metabolic reconstructions through modified latin-hypercube sampling. AB - Genome-Scale Metabolic Reconstructions (GSMRs), along with optimization-based methods, predominantly Flux Balance Analysis (FBA) and its derivatives, are widely applied for assessing and predicting the behavior of metabolic networks upon perturbation, thereby enabling identification of potential novel drug targets and biotechnologically relevant pathways. The abundance of alternate flux profiles has led to the evolution of methods to explore the complete solution space aiming to increase the accuracy of predictions. Herein we present a novel, generic algorithm to characterize the entire flux space of GSMR upon application of FBA, leading to the optimal value of the objective (the optimal flux space). Our method employs Modified Latin-Hypercube Sampling (LHS) to effectively border the optimal space, followed by Principal Component Analysis (PCA) to identify and explain the major sources of variability within it. The approach was validated with the elementary mode analysis of a smaller network of Saccharomyces cerevisiae and applied to the GSMR of Pseudomonas aeruginosa PAO1 (iMO1086). It is shown to surpass the commonly used Monte Carlo Sampling (MCS) in providing a more uniform coverage for a much larger network in less number of samples. Results show that although many fluxes are identified as variable upon fixing the objective value, majority of the variability can be reduced to several main patterns arising from a few alternative pathways. In iMO1086, initial variability of 211 reactions could almost entirely be explained by 7 alternative pathway groups. These findings imply that the possibilities to reroute greater portions of flux may be limited within metabolic networks of bacteria. Furthermore, the optimal flux space is subject to change with environmental conditions. Our method may be a useful device to validate the predictions made by FBA-based tools, by describing the optimal flux space associated with these predictions, thus to improve them. PMID- 26818784 TI - Facile Access to Graphene Oxide from Ferro-Induced Oxidation. AB - Methods allowing the oxidation of graphite to graphene oxide (GO) are vital important for the production of graphene from GO. This oxidation reaction has mainly relied on strong acid strategy for 174 years, which circumvents issues associated with toxicity of reagent and product, complex post-treatment, high cost and waste generation. Here, we report a green route for performing this oxidization reaction via a ferro-induced strategy, with use of water, potassium ferrate (Fe(VI)) and hydrogen peroxide (H2O2) as reagents, to produce about 65% yield of GO (vs. 40% for Hummers' method, the most commonly used concentrated acid strategy) and non-toxic by-products. Moreover, GO produced from this new method shows equivalent performance to those reported previously. This H2SO4-free strategy makes it possible to process graphite into GO in a safe, low-cost, time saving, energy-efficient and eco-friendly pathway, opening a promising avenue for the large-scale production of GO and GO-based materials. PMID- 26818783 TI - The cast of clasts: catabolism and vascular invasion during bone growth, repair, and disease by osteoclasts, chondroclasts, and septoclasts. AB - Three named cell types degrade and remove skeletal tissues during growth, repair, or disease: osteoclasts, chondroclasts, and septoclasts. A fourth type, unnamed and less understood, removes nonmineralized cartilage during development of secondary ossification centers. "Osteoclasts," best known and studied, are polykaryons formed by fusion of monocyte precursors under the influence of colony stimulating factor 1 (CSF)-1 (M-CSF) and RANKL. They resorb bone during growth, remodeling, repair, and disease. "Chondroclasts," originally described as highly similar in cytological detail to osteoclasts, reside on and degrade mineralized cartilage. They may be identical to osteoclasts since to date there are no distinguishing markers for them. Because osteoclasts also consume cartilage cores along with bone during growth, the term "chondroclast" might best be reserved for cells attached only to cartilage. "Septoclasts" are less studied and appreciated. They are mononuclear perivascular cells rich in cathepsin B. They extend a cytoplasmic projection with a ruffled membrane and degrade the last transverse septum of hypertrophic cartilage in the growth plate, permitting capillaries to bud into it. To do this, antiangiogenic signals in cartilage must give way to vascular trophic factors, mainly vascular endothelial growth factor (VEGF). The final cell type excavates cartilage canals for vascular invasion of articular cartilage during development of secondary ossification centers. The "clasts" are considered in the context of fracture repair and diseases such as arthritis and tumor metastasis. Many observations support an essential role for hypertrophic chondrocytes in recruiting septoclasts and osteoclasts/chondroclasts by supplying VEGF and RANKL. The intimate relationship between blood vessels and skeletal turnover and repair is also examined. PMID- 26818786 TI - Optical and morphological properties of thin films of bis-pyrenyl pi-conjugated molecules. AB - 1,4-Di-n-octyloxy-2,5-bis(pyren-1-ylethenyl)benzene (bis-pyrene) has been studied by the means of surface cavity ring-down (s-CRD) spectroscopy on an amorphous BK7 glass substrate and scanning tunnelling microscopy (STM) on Au(111). Absorption spectra show a modification of the optical properties as a function of coverage, i.e. appearance of a shoulder around 505 nm followed by a saturation of the intensity of this signal observed at higher coverages. We attribute this shoulder to the change of the molecular orientation between the first and the second monolayer and thus to an interfacial effect. These results are confirmed by scanning tunnelling microscopy (STM) measurements where the bis-pyrene molecules have been deposited on Au(111) at room temperature (RT) and onto a cold substrate. Independently of the temperature in the range from 210 K to RT, the first monolayer is always highly organized. At low temperature bis-pyrene molecules constituting the second monolayer are randomly distributed, suggesting that self-organisation is kinetically hindered. Deposited at room temperature, the molecular diffusion is enhanced and the formation of an organized second layer takes place after storing the sample for 150 minutes at room temperature. A HOMO-LUMO gap of 2.85 eV has been determined by scanning tunnelling spectroscopy, which is in very good agreement with the observed optical transition at 434 nm (2.86 eV) in s-CRD spectroscopy. PMID- 26818785 TI - Microarchitecture and Peripheral BMD are Impaired in Postmenopausal White Women With Fracture Independently of Total Hip T-Score: An International Multicenter Study. AB - Because single-center studies have reported conflicting associations between microarchitecture and fracture prevalence, we included high-resolution peripheral quantitative computed tomography (HR-pQCT) data from five centers worldwide into a large multicenter analysis of postmenopausal women with and without fracture. Volumetric BMD (vBMD) and microarchitecture were assessed at the distal radius and tibia in 1379 white postmenopausal women (age 67 +/- 8 years); 470 (34%) had at least one fracture including 349 with a major fragility fracture. Age, height, weight, and total hip T-score differed across centers and were employed as covariates in analyses. Women with fracture had higher BMI, were older, and had lower total hip T-score, but lumbar spine T-score was similar between groups. At the radius, total and trabecular vBMD and cortical thickness were significantly lower in fractured women in three out of five centers, and trabecular number in two centers. Similar results were found at the tibia. When data from five centers were combined, however, women with fracture had significantly lower total, trabecular, and cortical vBMD (2% to 7%), lower trabecular number (4% to 5%), and thinner cortices (5% to 6%) than women without fracture after adjustment for covariates. Results were similar at the radius and tibia. Similar results were observed with analysis restricted to major fragility fracture, vertebral and hip fractures, and peripheral fracture (at the radius). When focusing on osteopenic women, each SD decrease of total and trabecular vBMD was associated with a significantly increased risk of major fragility fracture (OR = 1.55 to 1.88, p < 0.01) after adjustment for covariates. Moreover, trabecular architecture modestly improved fracture discrimination beyond peripheral total vBMD. In conclusion, we observed differences by center in the magnitude of fracture/nonfracture differences at both the distal radius and tibia. However, when data were pooled across centers and the sample size increased, we observed significant and consistent deficits in vBMD and microarchitecture independent of total hip T score in all postmenopausal white women with fracture and in the subgroup of osteopenic women, compared to women who never had a fracture. (c) 2016 American Society for Bone and Mineral Research. PMID- 26818787 TI - HosA, a MarR Family Transcriptional Regulator, Represses Nonoxidative Hydroxyarylic Acid Decarboxylase Operon and Is Modulated by 4-Hydroxybenzoic Acid. AB - Members of the Multiple antibiotic resistance Regulator (MarR) family of DNA binding proteins regulate transcription of a wide array of genes required for virulence and pathogenicity of bacteria. The present study reports the molecular characterization of HosA (Homologue of SlyA), a MarR protein, with respect to its target gene, DNA recognition motif, and nature of its ligand. Through a comparative genomics approach, we demonstrate that hosA is in synteny with nonoxidative hydroxyarylic acid decarboxylase (HAD) operon and is present exclusively within the mutS-rpoS polymorphic region in nine different genera of Enterobacteriaceae family. Using molecular biology and biochemical approach, we demonstrate that HosA binds to a palindromic sequence downstream to the transcription start site of divergently transcribed nonoxidative HAD operon and represses its expression. Furthermore, in silico analysis showed that the recognition motif for HosA is highly conserved in the upstream region of divergently transcribed operon in different genera of Enterobacteriaceae family. A systematic chemical search for the physiological ligand revealed that 4 hydroxybenzoic acid (4-HBA) interacts with HosA and derepresses HosA mediated repression of the nonoxidative HAD operon. Based on our study, we propose a model for molecular mechanism underlying the regulation of nonoxidative HAD operon by HosA in Enterobacteriaceae family. PMID- 26818788 TI - Enhanced room temperature NO2 response of NiO-SnO2 nanocomposites induced by interface bonds at the p-n heterojunction. AB - Recently, heterostructured nanomaterials have attracted great attention in gas sensing applications. However, the sensing mechanism of the enhanced sensitivity of heterostructured nanomaterials remains unclear, which is not conducive to further improvements in their sensing performances. In order to detail the fundamental studies on the gas sensing mechanism of heterostructured nanomaterials and improve the room temperature NO2 sensing properties of NiO based nanomaterials, NiO-SnO2 heterojunction nanocomposites were fabricated. It was found that the sensitivity of the nanocomposites was largely enhanced compared to the bare NiO. On the basis of the intrinsic characteristics of the p n heterojunction and the band structure of the NiO-SnO2 heterojunction, the largely enhanced room temperature NO2 response of the nanocomposites could be attributed to two factors. One was the significantly decreased initial conductance, and the increase in the equivalent hole concentration of the nanocomposites after exposure to NO2, associated with the effective electron transfer via the interface bonds at the heterojunction. Another was that the variation of contact potential in the nanocomposites, before and after exposure to NO2, exerted a drastic effect on the transducer function for gas sensing. According to the differentiation in the sensitivity of the nanocomposites with different molar ratios, the important role of interface bonds in gas sensing properties was further illustrated by the dependency of the sensitivity on the interface bond number and the interface resistance. Here, we hope that this work could give us a better understanding of the gas sensing mechanism of the p-n heterojunction, and provide a proper approach for heterojunction materials to further improve their sensing performances. PMID- 26818789 TI - Biodegradable liposome-encapsulated hydrogels for biomedical applications: a marriage of convenience. AB - Hydrogels are hydrophilic three-dimensional networks with demonstrated potential for medical and pharmaceutical applications. Specifically, biopolymer-based hydrogels offer certain advantages over synthetic polymers in terms of biocompatibility and biodegradability. Because of their inherent properties, hydrogels are able to efficiently encapsulate and liberate in a controlled release manner, different hydrophobic and hydrophilic therapeutic molecules, including nucleic acids, proteins and antibodies. Several strategies have been reported in the literature to minimize the potential burst release of encapsulated drugs, thus preventing their local accumulation and consequent toxic responses. Within this context, liposomes embedded in hydrogels have emerged as an attractive strategy to reduce this undesirable effect. This tutorial review covers a selection of the most promising cationic, neutral and anionic biopolymer based hydrogels containing liposomes, niosomes or vesicles for drug delivery or tissue engineering applications. PMID- 26818790 TI - Patterns of recruitment to the specialty of obstetrics and gynaecology. PMID- 26818791 TI - Population genetics for 17 Y-STR loci in Korean ethnic minority from Liaoning Province, Northeast China. PMID- 26818792 TI - The associations of morningness-eveningness with anger and impulsivity in the general population. AB - The aim of this study was to investigate the relationships among morningness eveningness, impulsivity and anger in the general population. A total of 1000 community-dwelling subjects (500 males) aged 20-77 years (mean+/- SD age: 39.6 +/ 11.6 years) completed the morningness-eveningness questionnaire (MEQ), Barratt impulsiveness scale (BIS), Spielberger State-Trait Anger Expression Inventory (STAXI) and Center for Epidemiologic Studies Depression Scale. Moderation and mediation analyses were performed to determine whether the relationship between two variables depended on the third variable, referred to as a moderator, and whether the third variable, known as a mediator, was associated with the other two variables establishing causation. The MEQ scores exhibited significant negative associations with BIS (p < 0.001) and STAXI (p < 0.001) scores, and high scores on the BIS were associated with high scores on the STAXI (p < 0.001). Impulsivity, as measured by the BIS, played a role as a moderator (p < 0.001) in the relationship between MEQ and STAXI, and anger, as measured by the STAXI, acted as moderator (p = 0.030) in the association between MEQ and BIS. However, after controlling for the interaction of the BIS and MEQ, the MEQ scores did not significantly predict STAXI scores (p = 0.070). Additionally, the effect size of the mediating effect of the BIS scores on the relationship between the MEQ and STAXI (percent mediation: 53.2%) was larger than that of the STAXI scores on the association between the MEQ and BIS (percent mediation: 31.8%). The present results demonstrate that morningness-eveningness was closely related with both impulsivity and anger in the general population. Furthermore, these findings suggest that impulsivity may exercise a great influence on the association between morningness-eveningness and anger in two ways: as a moderator by modulating this relationship based on the level of impulsivity and as a mediator by acting as an intermediary factor. PMID- 26818793 TI - Functionally Guided Retinal Protective Therapy for Dry Age-Related Macular and Inherited Retinal Degenerations: A Pilot Study. AB - PURPOSE: To review the results of retinal function testing in eyes undergoing panmacular subthreshold diode micropulse laser (SDM) prophylaxis for chronic progressive retinal disease. METHODS: The records of all patients undergoing prophylactic panmacular SDM for high-risk age-related macular degeneration (AMD) and inherited photoreceptor degenerations (IRDs) examined by pattern electroretinography (PERG), automated microperimetry (AMP), and Central Vision Analyzer (CVA) testing before and after treatment were reviewed. RESULTS: A total of 158 consecutive eyes of 108 patients with AMD and 10 consecutive eyes of 8 patients with IRDs, evaluated both before and after SDM by PERG, were eligible for study. The IRD diagnoses included rod-cone degeneration (four eyes), cone-rod degeneration (three eyes), and Stargardt's disease (three eyes). In AMD, AMP was performed in 40 consecutive eyes, and CVA in the subsequent 73 consecutive eyes concurrent with PERG. The SDM treatment consisted of 1800 to 3000 confluent spots throughout the retina circumscribed by the major vascular arcades, including the fovea ("panmacular"). Testing was performed 1 week before and by 1 month after treatment. Results indicated that 149/168 eyes were improved by primary PERG measures: 139/158 eyes with AMD by PERG low-contrast scan Magnitude D (MagD)(MUV)/Magnitude (Mag)(MUV) ratios (P = 0.0001) and 10/10 eyes with IRDs by 240 concentric ring scan MagD(MUV)/Mag(MUV) ratios (P = 0.002). Snellen visual acuity (VA) was unchanged, but macular sensitivity by AMP (P = 0.0439) and mesopic contrast VA by CVA (P = 0.006) were improved. There were no adverse treatment effects. CONCLUSIONS: Our findings suggest a role for SDM as retinal protective therapy in chronic progressive retinal diseases. Pattern electroretinography enables (early, preventive) functionally guided, rather than (late, therapeutic) image-guided, disease management. PMID- 26818794 TI - Using Silent Substitution to Track the Mesopic Transition From Rod- to Cone-Based Vision in Mice. AB - PURPOSE: To describe the activity of rods and cones in visually intact mice in mesopic conditions, and establish the relative importance of each photoreceptor type in defining the transition from rod to cone vision. METHODS: Using mice (Opn1mwR) carrying a red-shifted cone opsin, we applied silent substitution methods to record light-adapted ERGs to flash stimuli visible only to rods or cones across a range of light levels (corneal irradiance 109-1014 photons/cm2/s; ~100-106 photoisomerisations/rod/s). We tested the impact of selectively changing the background light intensity as experienced by cones on the rod ERG (and vice versa) by adjusting the spectral composition of stimuli. The ERG parameters (b wave amplitude and implicit time, oscillatory power) were extracted, and their relationship to background intensity and the effective irradiance for cones versus rods/melanopsin was established. We also attempted to record a melanopsin ERG by using modifications of the rod-isolating stimuli. RESULTS: We saw the predicted decay and increase in rod- and cone-ERG amplitude, respectively, as a function of background intensity. There was only a single irradiance (1013 photons/cm2/s) at which both ERGs had high amplitude. Adjustments in the effective irradiance for rods/melanopsin did not impact the cone ERG except at the brightest backgrounds at which there was a melanopsin-dependent suppression of b-wave amplitude. Increasing effective irradiance for cones suppressed rod b wave amplitude across all background intensities. In addition, we were unable to record a melanopsin ERG. CONCLUSIONS: The cone measure of irradiance was particularly important in driving the transition from rod- to cone-based vision across mesopic light levels. PMID- 26818795 TI - The Carpentier-Edwards Perimount Magna mitral valve bioprosthesis: intermediate term efficacy and durability. AB - BACKGROUND: The Carpentier-Edwards Perimount Magna mitral valve bioprosthesis (Edwards Lifesciences, Irvine, CA) is a low-profile version of the earlier Perimount valve that uses the ThermaFix process for enhanced calcium removal. The Magna valve has been in use since 2008, yet no publication, until now, has verified its intermediate-term safety and efficacy. METHODS: From 2008 through 2011 (our 4-year study period), 70 Magna valves were implanted in the mitral position at a single institution (the Cleveland Clinic). Echocardiograms were prospectively interpreted. For this study, we reviewed patients' charts; endpoints included hemodynamic measurements, in-hospital morbidity and mortality, valve-related events, resource utilization, and 5-year survival rates. RESULTS: The mean patient age was 68 years; 43 % of the patients had New York Heart Association (NYHA) class III or IV disease, and 51.4 % had moderately severe, or worse, mitral regurgitation (MR). For 43 % of the patients, the Magna valve implantation was a reoperation. For 83 %, the Magna valve implantation also included a concomitant cardiac procedure. The median survival rate was 4.7 years and 90 % of patients were free from significant structural valve degeneration at 5 years. Preoperative atrial fibrillation, ischemic MR, intraaortic balloon pump placement, cardiogenic shock, cardiac arrest, and renal failure were associated with increased mortality. Right ventricular systolic pressure decreased from 50 mmHg preoperatively to 40 mmHg postoperatively, according to our matched-pair analysis (P = 0.003). Per their final echocardiogram during our study period, 98 % of surviving patients had trivial or no MR, one patient had mild MR, and one patient had severe MR. CONCLUSIONS: Our 5-year experience indicates that the Magna valve offers excellent intermediate-term durability and substantial echocardiographic improvement; its low-profile design make it ideal for reoperations and for concomitant cardiac procedures, including valve replacement. PMID- 26818796 TI - Adenylylation of Tyr77 stabilizes Rab1b GTPase in an active state: A molecular dynamics simulation analysis. AB - The pathogenic pathway of Legionella pneumophila exploits the intercellular vesicle transport system via the posttranslational attachment of adenosine monophosphate (AMP) to the Tyr77 sidechain of human Ras like GTPase Rab1b. The modification, termed adenylylation, is performed by the bacterial enzyme DrrA/SidM, however the effect on conformational properties of the molecular switch mechanism of Rab1b remained unresolved. In this study we find that the adenylylation of Tyr77 stabilizes the active Rab1b state by locking the switch in the active signaling conformation independent of bound GTP or GDP and that electrostatic interactions due to the additional negative charge in the switch region make significant contributions. The stacking interaction between adenine and Phe45 however, seems to have only minor influence on this stabilisation. The results may also have implications for the mechanistic understanding of conformational switching in other signaling proteins. PMID- 26818798 TI - High maternal sodium intake alters sex-specific renal renin-angiotensin system components in newborn Wistar offspring. AB - This study aimed to evaluate the systemic and renal renin-angiotensin-aldosterone system (RAAS) at birth in male and female offspring and in mothers fed a high sodium diet (HSD) before and during gestation. Female Wistar rats were fed a HSD (8.0% NaCl) or a normal sodium diet (1.3% NaCl) from 8 weeks of age until delivery of their first litter. Maternal body weight, tail blood pressure, and food and water intake were evaluated. The litter sizes were assessed, and the body and kidney weights of the offspring were measured. Both mothers and offspring were euthanized immediately following the birth of the pups to evaluate plasma renin activity (PRA), renal renin content (RRC), renal angiotensin converting enzyme (ACE) activity, renal angiotensin (Ang) II content, serum aldosterone (ALDO) levels, and renal cortical and medullary renin messenger RNA expression. In mothers in the HSD group, water intake and kidney mass were higher, whereas renal ACE activity, Ang II, PRA, ALDO and RRC were decreased. In the offspring of HSD-fed dams, the body and kidney mass were lower in both genders, renal ACE activity was lower in females and renal Ang II was lower in males. PRA, RRC, renin gene expression and ALDO levels did not differ between the groups of offspring. The data presented herein showed that a maternal HSD during pregnancy induces low birth weight and a sex-specific response in the RAAS in offspring. PMID- 26818797 TI - Cytotoxic Rocaglate Derivatives from Leaves of Aglaia perviridis. AB - Rocaglates are a series of structurally complex secondary metabolites with considerable cytotoxicity that have been isolated from plants of the Aglaia genus (Meliaceae). A new rocaglate (aglapervirisin A, 1) and its eight new biosynthetic precursors of rocaglate (aglapervirisins B-J, 2-9) together with five known compounds, were isolated from the leaves of Aglaia perviridis. Their structures were elucidated based on a joint effort of spectroscopic methods [IR, UV, MS, ECD, 1D- and 2D-NMR, HRESIMS], chemical conversion and single-crystal X-ray diffraction. Among these isolates, three (1, 10-11) were silvestrols, a rare subtype rocaglates, exhibiting notable cytotoxicity against four human tumor cell lines, with IC50 values between 8.0 and 15.0 nM. Aglapervirisin A (1) induces cell cycle arrest at the G2/M-phase boundary at concentration 10 nM accompanied by reductions in the expression levels of Cdc2 and Cdc25C in HepG2 cells after 72h co-incubation, and further induces the apoptosis of HepG2 cells at concentrations over 160 nM. PMID- 26818799 TI - Artificial Organs: Are the Costs Sustainable? PMID- 26818800 TI - Successful Insertion of a Tunneled Cuffed Catheter Into the Inferior Vena Cava in a Patient With a Right Atrial Thrombus. PMID- 26818802 TI - Generalized logical model based on network topology to capture the dynamical trends of cellular signaling pathways. AB - BACKGROUND: Cellular responses to extracellular perturbations require signaling pathways to capture and transmit the signals. However, the underlying molecular mechanisms of signal transduction are not yet fully understood, thus detailed and comprehensive models may not be available for all the signaling pathways. In particular, insufficient knowledge of parameters, which is a long-standing hindrance for quantitative kinetic modeling necessitates the use of parameter free methods for modeling and simulation to capture dynamic properties of signaling pathways. RESULTS: We present a computational model that is able to simulate the graded responses to degradations, the sigmoidal biological relationships between signaling molecules and the effects of scheduled perturbations to the cells. The simulation results are validated using experimental data of protein phosphorylation, demonstrating that the proposed model is capable of capturing the main trend of protein activities during the process of signal transduction. Compared with existing simulators, our model has better performance on predicting the state transitions of signaling networks. CONCLUSION: The proposed simulation tool provides a valuable resource for modeling cellular signaling pathways using a knowledge-based method. PMID- 26818803 TI - Moving On Up: H(+)-PPase Mediated Crop Improvement. AB - Upregulation of H(+)-PPase in diverse crop systems triggers agriculturally beneficial phenotypes including augmented stress tolerance, improved water and nutrient use efficiencies, and increased biomass and yield. We argue that further research is warranted to maximize the full potential of this simple and successful biotechnology. PMID- 26818804 TI - Management of resistant hypertension: expert consensus statement from the French Society of Hypertension, an affiliate of the French Society of Cardiology. AB - To improve the management of resistant hypertension, the French Society of Hypertension, an affiliate of the French Society of Cardiology, has published a set of eleven recommendations. The primary objective is to provide the most up-to date information based on the strongest scientific rationale and that is easily applicable to daily clinical practice. Resistant hypertension is defined as uncontrolled blood pressure on office measurements and confirmed by out-of-office measurements despite a therapeutic strategy comprising appropriate lifestyle and dietary measures and the concurrent use of three antihypertensive agents including a thiazide diuretic, a renin-angiotensin system blocker (ARB or ACEI) and a calcium channel blocker, for at least 4 weeks, at optimal doses. Treatment compliance must be closely monitored, as must factors that are likely to affect treatment resistance (excessive dietary salt intake, alcohol, depression, drug interactions and vasopressor drugs). If the diagnosis of resistant hypertension is confirmed, the patient should be referred to a hypertension specialist to screen for potential target organ damage and secondary causes of hypertension. The recommended treatment regimen is a combination therapy comprising four treatment classes, including spironolactone (12.5-25 mg per day). In the event of a contraindication or a non-response to spironolactone, or if adverse effects occur, a beta-blocker, an alpha-blocker, or a centrally acting antihypertensive drug should be prescribed. Because renal denervation is still undergoing assessment for the treatment of hypertension, this technique should only be prescribed by a specialist hypertension clinic. PMID- 26818805 TI - Long-term effects of multielectrode renal denervation on cardiac adaptations in resistant hypertensive patients with left ventricular hypertrophy. AB - Left ventricular (LV) hypertrophy and diastolic dysfunction predict long-term cardiovascular events. We evaluated whether multielectrode renal denervation (RDN) can provide beneficial cardiac adaptations in patients with resistant hypertension and LV hypertrophy long term at 24 months. Seventeen patients with true drug-resistant hypertension (age: 57+/-9 years, 11 men, body mass index: 33.79+/-5.49 kg m-2, office blood pressure (BP): 183+/-20/97+/-18 mm Hg and ambulatory BP: 152+/-16/86+/-15 mm Hg receiving 4.5 anti-hypertensive drugs per day) and LV hypertrophy underwent multielectrode RDN (EnligHTNTM, St Jude Medical). At baseline, LV mass index averaged 141.1+/-16.8 g m-2 (58.4+/-7.8 g m 2.7) and mitral lateral E/E' 14.7+/-6.2. At 6, 12 and 24 months after RDN, the LV mass/body surface area (LV mass per height2.7) reduced significantly by 9.1% (8.8%), 11.3% (10.5%) and 15.5% (14.1%), respectively; and the mitral lateral E/E' reduced significantly by 14.0%, 15.3% and 29.7%, respectively. At 24 months after RDN, majority (70.6%) of the patients showed regression of LV hypertrophy of at least one level; the proportion of patients with concentric LV hypertrophy had dropped by 47.1% from baseline; and the proportion of patients with office systolic BP level of ?160 mm Hg had dropped by 76.5% from baseline. No statistically significant association was observed between the changes in office BP and the changes in LV mass index or diastolic function. In patients with drug resistant hypertension and LV hypertrophy, multielectrode RDN can contribute to significant and sustained improvements of diastolic dysfunction and attenuation of LV mass indices long term at 24 months. PMID- 26818806 TI - Arsenate removal by layered double hydroxides embedded into spherical polymer beads: Batch and column studies. AB - In this study, the performance of poly(layered double hydroxides) [poly(LDHs)] beads as an adsorbent for arsenate removal from aqueous solution was investigated. The poly(LDHs) beads were prepared by immobilizing LDHs into spherical alginate/polyvinyl alcohol (PVA)-glutaraldehyde beads (spherical polymer beads). Batch adsorption studies were conducted to assess the effect of contact time, solution pH, initial arsenate concentrations and co-existing anions on arsenate removal performance. The potential reuse of these poly(LDHs) beads was also investigated. Approximately 79.1 to 91.2% of arsenic was removed from an arsenate solution (50 mg As L(-1)) by poly(LDHs). The adsorption data were well described by the pseudo-second-order kinetics model and the Langmuir isotherm model, and the adsorption capacities of these poly(LDHs) beads at pH 8 were from 1.64 to 1.73 mg As g(-1), as calculated from the Langmuir adsorption isotherm. The adsorption ability of the poly(LDHs) beads decreased by approximately 5-6% after 5 adsorption-desorption cycles. Phosphates markedly decreased arsenate removal. The effect of co-existing anions on the adsorption capacity declined in the following order: HPO4 (2-) >> HCO3 (-) > SO4 (2-) > Cl(-). A fixed-bed column study was conducted with real-life arsenic-containing water. The breakthrough time was found to be from 7 to 10 h. Under optimized conditions, the poly(LDHs) removed more than 82% of total arsenic. The results obtained in this study will be useful for further extending the adsorbents to the field scale or for designing pilot plants in future studies. From the viewpoint of environmental friendliness, the poly(LDHs) beads are a potential cost-effective adsorbent for arsenate removal in water treatment. PMID- 26818808 TI - Medication-related osteonecrosis of the jaw associated with bisphosphonates and denosumab in osteoporosis. AB - OBJECTIVE: To describe the clinical characteristics and evolution of our series of medication-related osteonecrosis of the jaws (MRONJ) associated with denosumab in osteoporotic patients. MATERIAL AND METHODS: We present 10 new cases of MRONJ in patients receiving denosumab for osteoporosis. We describe the mean doses of denosumab, previous bisphosphonate intake, and the clinical characteristics associated with the osteonecrosis, such as local contributing factors, symptoms, and evolution after treatment. RESULTS: The mean number of denosumab doses was 3.4 +/- 2.2. In 90% of patients, there was a prior history of oral bisphosphonate intake, with a mean duration of 46.78 +/- 25.11 months. The most common local factor was dental extraction (6 cases; 60%), and most cases had necrotic bone exposure (9/10, 90%). Sclerosis of the bone was the most common radiographic finding. Stage 1 was the most common ONM stage, found in 80%. 'Cure' after conservative treatments was obtained in 71.4%. CONCLUSIONS: Most of our cases were in the early stages of MRONJ, and the success rate after conservative treatment was high. PMID- 26818807 TI - Involvement of resistin-like molecule beta in the development of methionine choline deficient diet-induced non-alcoholic steatohepatitis in mice. AB - Resistin-like molecule beta (RELMbeta) reportedly has multiple functions including local immune responses in the gut. In this study, we investigated the possible contribution of RELMbeta to non-alcoholic steatohepatitis (NASH) development. First, RELMbeta knock-out (KO) mice were shown to be resistant to methionine-choline deficient (MCD) diet-induced NASH development. Since it was newly revealed that Kupffer cells in the liver express RELMbeta and that RELMbeta expression levels in the colon and the numbers of RELMbeta-positive Kupffer cells were both increased in this model, we carried out further experiments using radiation chimeras between wild-type and RELMbeta-KO mice to distinguish between the contributions of RELMbeta in these two organs. These experiments revealed the requirement of RELMbeta in both organs for full manifestation of NASH, while deletion of each one alone attenuated the development of NASH with reduced serum lipopolysaccharide (LPS) levels. The higher proportion of lactic acid bacteria in the gut microbiota of RELMbeta-KO than in that of wild-type mice may be one of the mechanisms underlying the lower serum LPS level the former. These data suggest the contribution of increases in RELMbeta in the gut and Kupffer cells to NASH development, raising the possibility of RELMbeta being a novel therapeutic target for NASH. PMID- 26818809 TI - The Clinical and Cost Effectiveness of Ustekinumab for the Treatment of Psoriatic Arthritis: A Critique of the Evidence. AB - The National Institute for Health and Care Excellence (NICE) invited the manufacturer of ustekinumab (Janssen) to submit evidence for the clinical and cost effectiveness of ustekinumab for the treatment of active psoriatic arthritis (PsA) as part of the Institute's single technology appraisal (STA) process. The Centre for Reviews and Dissemination and the Centre for Health Economics Technology Appraisal Group at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the ERG review of the manufacturer's evidence submission, and summarises the NICE Appraisal Committee's final guidance (TA340) issued in June 2015. The manufacturer presented evidence on ustekinumab for two patient populations: (1) a tumour necrosis factor-alpha (TNFalpha)-inhibitor-naive population who had not previously received any TNFalpha inhibitors (biologics); and (2) a TNFalpha inhibitor-exposed population who had previously received at least one TNFalpha inhibitor. The clinical evidence for ustekinumab was derived from two randomised controlled trials (PSUMMIT 1 and 2), in which a total of 927 patients who had not responded to previous disease-modifying antirheumatic drug therapies received ustekinumab 45 mg, ustekinumab 90 mg, or placebo. These data suggested that ustekinumab is more effective than placebo over 16-24 weeks in terms of both joint and skin response. In the absence of head-to-head comparisons between different biologics (ustekinumab, golimumab, etanercept, adalimumab and infliximab), the manufacturer conducted a network meta-analysis to estimate the relative efficacy of treatments for the TNFalpha-inhibitor-naive population. Results of this analysis were marked as academic in confidence and are therefore not reported. For the TNFalpha-inhibitor-exposed population, the clinical analysis was limited to ustekinumab versus conventional management only, and was based on a subgroup of 180 patients from the PSUMMIT 2 trial. The ERG raised concerns relating to the lack of data on the long-term efficacy of ustekinumab, the limited data available for the exposed population, and the lack of consideration of the sequential use of treatments. Based on the manufacturer's original model, the ERG found ustekinumab to be dominated by golimumab in the anti-TNF-inhibitor-naive population, and had an incremental cost-effectiveness ratio (ICER) of L29,843/quality-adjusted life-years versus conventional management in the exposed population. The ERG's analyses highlighted the fact that there is significant uncertainty around the model results. In addition, the ERG's exploratory cost-effectiveness analysis, which incorporated the sequential use of TNFalpha inhibitors, suggested that ustekinumab would not be cost effective if it were used as second-line treatment. The initial NICE recommendations asserted that ustekinumab was not recommended for treating active PsA. However, the manufacturer submitted a post-consultation model that included a Patient Access Scheme (PAS), halving the unit cost of ustekinumab 90 mg to L2147 (the same as a 45 mg dose). The NICE final recommendations were that, dependent on the inclusion of the PAS, ustekinumab is recommended as an option, along or in combination with methotrexate, for treating active PsA in adults only when treatment with TNFalpha inhibitors is contraindicated but would otherwise be considered, or the person has previously had treatment with one or more TNFalpha inhibitors, which has failed. PMID- 26818810 TI - Human Airway Primary Epithelial Cells Show Distinct Architectures on Membrane Supports Under Different Culture Conditions. AB - To facilitate drug development for lung delivery, it is highly demanding to establish appropriate airway epithelial cell models as transport barriers to evaluate pharmacokinetic profiles of drug molecules. Besides the cancer-derived cell lines, as the primary cell model, normal human bronchial epithelial (NHBE) cells have been used for drug screenings because of physiological relevance to in vivo. Therefore, to accurately interpret drug transport data in NHBE measured by different laboratories, it is important to know biophysical characteristics of NHBE grown on membranes in different culture conditions. In this study, NHBE was grown on the polyester membrane in a different medium and its transport barrier properties as well as cell architectures were fully characterized by functional assays and confocal imaging throughout the days of cultures. Moreover, NHBE cells on inserts in a different medium were subject to either of air-interfaced culture (AIC) or liquid-covered culture (LCC) condition. Cells in the AIC condition were cultivated on the membrane with medium in the basolateral side only, whereas cells with medium in apical and basolateral sides under the LCC condition. Quantitative microscopic imaging with biophysical examination revealed distinct multilayered architectures of differentiated NHBE cells, suggesting NHBE as functional cell barriers for the lung-targeting drug transport. PMID- 26818811 TI - Differential impact of current diagnosis and clinical stage on attendance at a youth mental health service. AB - AIM: To examine whether clinical stage of illness and current diagnosis influence appointment behaviour in a specialized primary-level youth mental health service. METHODS: Factors associated with attendance at 8697 appointments made by 828 young people (females = 497) aged 12-25 years over a 1-year period were analysed. RESULTS: The number of appointments made did not correlate with the rates of attendance. However, those with more severe psychiatric morbidity made significantly more appointments and missed significantly more appointments than those with less severe presentations. Impaired social functioning was the best predictor of female attendance rates, whereas age and clinical stage of illness best predicted male attendance rates. Current diagnosis rather than functional impairment appeared to influence the level of input offered by clinicians. CONCLUSIONS: Age, gender, severity of illness, functioning and psychological distress had differential associations with both planned treatment intensity and attendance rates. These differences are likely to have implications for service provision in this youth population. PMID- 26818813 TI - Difficult case of Cronkhite-Canada syndrome with small intestinal bacterial overgrowth, Clostridium difficile infection and polymyalgia rheumatica. AB - A 64-year-old woman presented with heavy diarrhoea, nausea and weight loss accompanied by alopecia and dystrophic fingernails and toenails. The preceding diagnosis of an inflammatory bowel disease, a common pitfall, was excluded by endoscopic work up. Instead, Cronkhite-Canada syndrome (CCS), a rare polyposis condition, was identified as the reason for this almost pathognomonic combination of diagnostic findings including various polyps throughout the entire intestine and ectodermal abnormalities. This case exemplifies common risks and complications in terms of gastrointestinal malabsorption, infections and small intestinal bacterial overgrowth (SIBO), including its treatment as well as a hereto unreported association with polymyalgia rheumatica. In CCS, long-term immunosuppressive therapy and close endoscopic cancer screening of the patient is essential. The treatment of vitamin deficiency and recurring SIBO helps to reduce symptoms. PMID- 26818812 TI - SLK/LOSK kinase regulates cell motility independently of microtubule organization and Golgi polarization. AB - Cell motility is an essential complex process that requires actin and microtubule cytoskeleton reorganization and polarization. Such extensive rearrangement is closely related to cell polarization as a whole. The serine/threonine kinase SLK/LOSK is a potential regulator of cell motility, as it phosphorylates a series of cytoskeleton-bound proteins that collectively participate in the remodeling of migratory cell architecture. In this work, we report that SLK/LOSK is an indispensable regulator of cell locomotion that primarily acts through the small GTPase RhoA and the dynactin subunit p150(Glued). Both RhoA and dynactin affect cytoskeleton organization, polarization, and general cell locomotory activity to various extents. However, it seems that these events are independent of each other. Thus, SLK/LOSK kinase effectively functions as a switch that links all of the processes underlying cell motility to provide robust directional movement. PMID- 26818814 TI - The 'all-right' man: a case of three coronary arteries all arising from the right sinus of Valsalva. PMID- 26818815 TI - [Temporary evolutions of flies anopheles in high altitude region of Lwiro-Katana (Democratic Republic of the Congo)]. AB - This study has been done with the objective of knowing more about the Anopheles evolutions situation at Lwiro-Katana from 1967 up to 2014. On seven species identified in this region, only four were permanent in nine investigations done. The geometric average calculated shows the evolution of 3.152 for Anopheles funestus, 2.867 for An. gambiae, 2.663 for An. demeilloni and 2.441 for An. marshallii. These species share almost the same ecological conditions for their larval development found in different kinds of water. These conditions were created by the anthropisation of the region followed by some activities. The increasing process attests that An. funestus, An. gambiae and An. demeilloni have an increasing tendency while An. marshallii has a decreasing tendency and is likely to approach the 0 level. An. coustani and An. christyi miss the stability development due to the environmental pertubations since 1980 in this environment. An. kingi wasn't identified after 1980. All of these species of anopheles share the same ecological niche and present a scientific interest. The knowledge of their evolution in this area is really very important because it helps to have better vector control. Also three of those mosquitos (An. gambiae, An. funestus and An. marshallii) are the greatest responsible of the killing paludism South of the Sahara. PMID- 26818816 TI - [Vingt-cinquieme reunion du comite local de la Societe de pathologie exotique, 24 novembre 2015]. PMID- 26818817 TI - [XXI(es) Actualites du Pharo 2015-Les vaccinations dans les pays en developpement Marseille 7, 8 et 9 octobre 2015]. PMID- 26818818 TI - Synthesis of inositol phosphate-based competitive antagonists of inositol 1,4,5 trisphosphate receptors. AB - Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca(2+) channels that are widely expressed in animal cells, where they mediate the release of Ca(2+) from intracellular stores evoked by extracellular stimuli. A diverse array of synthetic agonists of IP3Rs has defined structure-activity relationships, but existing antagonists have severe limitations. We combined analyses of Ca(2+) release with equilibrium competition binding to IP3R to show that (1,3,4,6)IP4 is a full agonist of IP3R1 with lower affinity than (1,4,5)IP3. Systematic manipulation of this meso-compound via a versatile synthetic scheme provided a family of dimeric analogs of 2-O-butyryl-(1,3,4,6)IP4 and (1,3,4,5,6)IP5 that compete with (1,4,5)IP3 for binding to IP3R without evoking Ca(2+) release. These novel analogs are the first inositol phosphate-based competitive antagonists of IP3Rs with affinities comparable to that of the only commonly used competitive antagonist, heparin, the utility of which is limited by off-target effects. PMID- 26818819 TI - X-ray induced singlet oxygen generation by nanoparticle-photosensitizer conjugates for photodynamic therapy: determination of singlet oxygen quantum yield. AB - Singlet oxygen is a primary cytotoxic agent in photodynamic therapy. We show that CeF3 nanoparticles, pure as well as conjugated through electrostatic interaction with the photosensitizer verteporfin, are able to generate singlet oxygen as a result of UV light and 8 keV X-ray irradiation. The X-ray stimulated singlet oxygen quantum yield was determined to be 0.79 +/- 0.05 for the conjugate with 31 verteporfin molecules per CeF3 nanoparticle, the highest conjugation level used. From this result we estimate the singlet oxygen dose generated from CeF3 verteporfin conjugates for a therapeutic dose of 60 Gy of ionizing radiation at energies of 6 MeV and 30 keV to be (1.2 +/- 0.7) * 10(8) and (2.0 +/- 0.1) * 10(9) singlet oxygen molecules per cell, respectively. These are comparable with cytotoxic doses of 5 * 10(7)-2 * 10(9) singlet oxygen molecules per cell reported in the literature for photodynamic therapy using light activation. We confirmed that the CeF3-VP conjugates enhanced cell killing with 6 MeV radiation. This work confirms the feasibility of using X- or gamma- ray activated nanoparticle photosensitizer conjugates, either to supplement the radiation treatment of cancer, or as an independent treatment modality. PMID- 26818820 TI - Translational-circular scanning for magneto-acoustic tomography with current injection. AB - BACKGROUND: Magneto-acoustic tomography with current injection involves using electrical impedance imaging technology. To explore the potential applications in imaging biological tissue and enhance image quality, a new scan mode for the transducer is proposed that is based on translational and circular scanning to record acoustic signals from sources. METHODS: An imaging algorithm to analyze these signals is developed in respect to this alternative scanning scheme. Numerical simulations and physical experiments were conducted to evaluate the effectiveness of this scheme. An experiment using a graphite sheet as a tissue mimicking phantom medium was conducted to verify simulation results. A pulsed voltage signal was applied across the sample, and acoustic signals were recorded as the transducer performed stepped translational or circular scans. The imaging algorithm was used to obtain an acoustic-source image based on the signals. RESULTS: In simulations, the acoustic-source image is correlated with the conductivity at the sample boundaries of the sample, but image results change depending on distance and angular aspect of the transducer. In general, as angle and distance decreases, the image quality improves. Moreover, experimental data confirmed the correlation. CONCLUSION: The acoustic-source images resulting from the alternative scanning mode has yielded the outline of a phantom medium. This scan mode enables improvements to be made in the sensitivity of the detecting unit and a change to a transducer array that would improve the efficiency and accuracy of acoustic-source images. PMID- 26818821 TI - Biocompatible Azide-Alkyne "Click" Reactions for Surface Decoration of Glyco Engineered Cells. AB - Bio-orthogonal copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) has been widely used to modify azide- or alkyne-bearing monosaccharides on metabolic glyco engineered mammalian cells. Here, we present a systematic study to elucidate the design space for the cytotoxic effects of the copper catalyst on NIH 3T3 fibroblasts and on HEK 293-F cells. Monitoring membrane integrity by flow cytometry and RT-PCR analysis with apoptotic and anti-apoptotic markers elucidated the general feasibility of CuAAC, with exposure time of the CuAAC reaction mixture having the major influence on biocompatibility. A high labeling efficiency of HEK 293-F cells with a fluorescent alkyne dye was rapidly achieved by CuAAC in comparison to copper free strain-promoted azide-alkyne cycloaddition (SPAAC). The study details effective and biocompatible conditions for CuAAC-based modification of glyco-engineered cells in comparison to its copper free alternative. PMID- 26818822 TI - Comments Regarding Masroor et al: Perceptions and Barriers to Universal Gloving for Infection Prevention. PMID- 26818823 TI - Time in Development. Preface. PMID- 26818824 TI - Incorporating tree-thinking and evolutionary time scale into developmental biology. AB - Phylogenetic approaches are indispensable in any comparative molecular study involving multiple species. These approaches are in increasing demand as the amount and availability of DNA sequence information continues to increase exponentially, even for organisms that were previously not extensively studied. Without the sound application of phylogenetic concepts and knowledge, one can be misled when attempting to infer ancestral character states as well as the timing and order of evolutionary events, both of which are frequently exerted in evolutionary developmental biology. The ignorance of phylogenetic approaches can also impact non-evolutionary studies and cause misidentification of the target gene or protein to be examined in functional characterization. This review aims to promote tree-thinking in evolutionary conjecture and stress the importance of a sense of time scale in cross-species comparisons, in order to enhance the understanding of phylogenetics in all biological fields including developmental biology. To this end, molecular phylogenies of several developmental regulatory genes, including those denoted as "cryptic pan-vertebrate genes", are introduced as examples. PMID- 26818825 TI - Autoimmune hemolytic anemia during bendamustine plus rituximab treatment in CLL patients: multicenter experience. PMID- 26818826 TI - What Do We Know Now About the Impact of the Laws Related to Marijuana? AB - OBJECTIVES: This study presents information on the status and impact of medical and legalized marijuana, and the latest data on attitudes and prevalence of use since implementation of these laws. Recent reports from epidemiologists in Denver and Seattle are summarized to give the readers a sense of the changes as these laws have taken effect in their communities. METHODS: The status of these laws is reviewed and the results of surveys taken before and after the laws were enacted are presented, along with data on changing potency and driving under the influence of marijuana. SUMMARY: Prevalence of use by youths has not increased, but their negative attitudes towards the risk of using marijuana have decreased, and use by adults has increased. Potency continues to increase, as has the proportion of drivers testing positive for use of the drug. Data from Denver show increases in hospital admissions, emergency department visits, and calls to poison centers, with decreasing arrests and admissions to substance abuse treatment programs. Data from the Seattle area show similar decreases in treatment admissions and police involvement, but also increased prevalence of more frequent use. CONCLUSIONS: Current data suggest that increases in marijuana use preceded legalization in 2012. Treatment admissions were declining before these laws, but some indicators of morbidity seem to be increasing subsequent to legalization, with modest increases in poison center calls in both states and increases in acute medical visits in Denver. Data are needed to understand the relationship between the patterns and amounts of use in terms of consequences, and data on the health conditions of those receiving medical marijuana and the impact of higher potency. PMID- 26818827 TI - Managing non-communicable diseases at health district level in Cambodia: a systems analysis and suggestions for improvement. AB - BACKGROUND: Cambodia developed its public health system along the principles of the district model and geared its services towards managing communicable diseases and maternal and child health issues. In line with other countries in the region, non-communicable diseases have emerged as a leading cause of adult mortality. We assessed the current capacity of the Cambodian district health system to manage hypertension and diabetes, with a focus on access to medicine for these chronic conditions. METHODS: A case study whereby in three purposely selected districts in an equal number of provinces a total of 74 informants were interviewed: 27 health care providers and administrators, 30 community representatives and 17 managers of specific non-communicable diseases interventions and social health protection schemes. Questions related to the World Health Organization's health system building blocks. Data analysis involved coding, indexing, charting and mapping the data. Following these exercises all information was analysed by kind of respondent and their respective answer to the question concerned. Responses by respondents of three groups of interviewees were compared when appropriate. At 14 health centres and 3 district hospitals the availability of key medicines for hypertension and diabetes in accordance with the National Essential Drug List was assessed. This was also done for essential tools and equipment to diagnose these two conditions. RESULTS: Although there was agreement amongst nearly all interviewees that non-communicable diseases were prevalent, the district health system, including all health systems building blocks and the referral system, was inadequately developed to effectively deal with these conditions. Medicines supply was erratic and the quantity provided allowed for few patients to be treated, for a short period only, mainly at secondary or tertiary level. CONCLUSIONS: Because of the public health, social and economic importance of non communicable diseases, a rapid response is required. Given the current Cambodian situation, such response may initially be a diagonal approach, with non communicable diseases services integrated in the National HIV/AIDS Programme. This should happen together with a reorientation of the health system to enable a horizontal approach to non-communicable diseases management in the long term. PMID- 26818828 TI - Neovascular glaucoma: a retrospective review from a tertiary center in China. AB - BACKGROUND: The purpose of this study is to report the prevalence, etiology, treatment and outcomes of neovascular glaucoma (NVG) in a tertiary care ophthalmic center in China. METHODS: Medical records of patients diagnosed as NVG at the Wenzhou Medical University between 2003 and 2014 were reviewed. Success was defined as IOP between 6 and 21 mmHg without topical or systemic glaucoma medications with retention of presenting visual acuity (VA). RESULTS: NVG was diagnosed in 483 of 8306 (5.8%) of all glaucoma patients. Etiology is reported for all 310 eyes of 284 patients managed in the department. Interventions depended on insurance as well as personal finances; outcomes are reported for the 149 eyes of 138 patients with complete data that met follow up requirements. Diabetic retinopathy (DR,39.7%) was the major cause of NVG. Kaplan Meier survival analysis showed a success rate of 84.8% at 1 year, 47.5% at 3 years and 21.9% at 5 years. Major interventions included glaucoma drainage device (GDD) in 103 eyes and trans-scleral cyclophotocoagulation (TSCPC) in 22 eyes. Complications were more common in the GDD group. CONCLUSIONS: NVG comprised 5.8% of glaucoma patients seen in a tertiary Chinese hospital. DR was identified as the commonest cause and probably reflects the increasing prevalence of diabetes in China. Surgical interventions were partly determined by insurance status and personal finances. GDD was the commonest surgical intervention used and also had the most complications. PMID- 26818829 TI - RARalpha mediates all-trans-retinoic acid-induced VEGF-C, VEGF-D, and VEGFR3 expression in lung cancer cells. AB - The regulation of vascular endothelial growth factors C (VEGF-C) and D (VEGF-D), and their receptor VEGFR3 gene and protein expression by all-trans-retinoic acid (atRA) in A549 lung cancer cells, was investigated. We showed that atRA treatment increased VEGF-C, VEGF-D, and VEGFR3 protein and mRNA contents in dose-dependent manner. atRA-mediated increase of both ligands and receptor expression correlated with the elevated level of retinoic acid receptor alpha (RARalpha) expression, while the level of another atRA receptor, peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta), was decreased. We demonstrated that the classical counterpart of RARalpha, retinoid X receptor alpha (RXRalpha), was down regulated in both cytoplasm and nucleus of A549 cells upon atRA addition. On the contrary, the nuclear quantity of another possible RARalpha counterpart, transcription factor Sp1, was increased after atRA treatment. PMID- 26818830 TI - Quality assurance in postgraduate pathology training the Dutch way: regular assessment, monitoring of training programs but no end of training examination. AB - It might seem self-evident that in the transition from a supervised trainee to an independent professional who is no longer supervised, formal assessment of whether the trainee knows his/her trade well enough to function independently is necessary. This would then constitute an end of training examination. Such examinations are practiced in several countries but a rather heterogeneous situation exists in the EU countries. In the Netherlands, the training program is not concluded by a summative examination and reasons behind this situation are discussed. Quality assurance of postgraduate medical training in the Netherlands has been developed along two tracks: (1) not a single testing moment but continuous evaluation of the performance of the trainee in 'real time' situations and (2) monitoring of the quality of the offered training program through regular site-visits. Regular (monthly and/or yearly) evaluations should be part of every self-respecting training program. In the Netherlands, these evaluations are formative only: their intention is to provide the trainee a tool by which he or she can see whether they are on track with their training schedule. In the system in the Netherlands, regular site-visits to training programs constitute a crucial element of quality assurance of postgraduate training. During the site-visit, the position and perceptions of the trainee are key elements. The perception by the trainee of the training program, the institution (or department) offering the training program, and the professionals involved in the training program is explicitly solicited and systematically assessed. With this two-tiered approach high-quality postgraduate training is assured without the need for an end of training examination. PMID- 26818831 TI - Doing more with less: fluorescence in situ hybridization and gene sequencing assays can be reliably performed on archival stained tumor tissue sections. AB - Little is known about molecular testing on tumor tissue retrieved from stained sections, for which there may be a clinical need. We retrospectively analyzed 112 sections from 56 tumor patients using either fluorescence in situ hybridization (FISH) with different probes (19 sections from 17 patients) or Sanger or targeted next generation sequencing for detection of BRAF, EGFR, KRAS, C-KIT, and TP53 mutations (93 sections from 39 patients). Tumor tissue sections had been stained by hematoxylin and eosin (H&E) (42 sections) or by immunohistochemistry for cytoplasmic or nuclear/nuclear-cytoplasmic markers (70 sections) with a peroxidase (P-IHC, with 3,3'-diaminobenzidine as chromogen) or alkaline phosphatase label (AP-IHC, with Warp RedTM as chromogen). For FISH analysis, the concordance rate between the original diagnosis and that obtained on H&E- or P IHC-stained tissue sections (AP-IHC was not on record for this set of patients) was 95% (18 out of 19 tumor sections). Only one tumor sample, diffusely positive for MLH1, did not yield any nuclear hybridization signal. For sequencing analysis, the concordance rate was 100% on negative P-IHC and positive AP-IHC stained sections, regardless of the subcellular localization of the reaction product. Mutations were detected in only 52% of cases expressing nuclear/nuclear cytoplasmic markers, regardless of the sequencing technology used (p = 0.0002). In conclusion, stained sections may be a valuable resource for FISH or sequencing analysis, but on cases expressing nuclear markers sequencing results need to be interpreted cautiously. PMID- 26818832 TI - Expression of the CXCR4 ligand SDF-1/CXCL12 is prognostically important for adenocarcinoma and large cell carcinoma of the lung. AB - The SDF-1/CXCR4 axis is associated with tumor progression and has been reported as a prognostic parameter, although with conflicting data for non-small cell lung cancer (NSCLC). This study examines a large cohort of clinically and pathologically well-characterized NSCLC patients and includes the activated form of CXCR4 (pCXCR4), which has not been studied in this context so far. SDF-1, CXCR4, and pCXCR4 were assessed immunohistochemically in 371 surgically resected NSCLC using a standardized tissue microarray platform. Extensive clinical and pathological data and a postoperative follow-up period of 17 years enabled detailed correlations. CXCR4 and pCXCR4 were frequently expressed on squamous cell carcinoma. Membranous expression of SDF-1 was a marker of poor prognosis and proved to be an independent prognostic parameter for the entire cohort and for patients with adenocarcinoma (ACA) and large cell carcinoma (LCC). Targeted cancer therapies blocking SDF-1/CXCR4 interaction already exist, and our data suggest that expression of SDF-1, especially on poorer prognosis subgroups of LCC and ACA, indicates patients that might benefit more than others. This should be taken into account when assessing the effectiveness of such targeted approaches for NSCLC patients and could lead to important implications. PMID- 26818833 TI - Consistency in recognizing microinvasion in breast carcinomas is improved by immunohistochemistry for myoepithelial markers. AB - Microinvasion is the smallest morphologically identifiable stage of invasion. Its presence and distinction from in situ carcinoma may have therapeutic implications, and clinical staging also requires the recognition of this phenomenon. Microinvasion is established on the basis of several morphological criteria, which may be difficult and not perfectly reproducible among pathologists. The aim of this study was to assess the consistency of diagnosing microinvasion in the breast on traditional haematoxylin and eosin (HE) stained slides and to evaluate whether immunohistochemistry (IHC) for myoepithelial markers could improve this. Digital images were generated from representative areas of 50 cases stained with HE and IHC for myoepithelial markers. Cases were specifically selected from the spectrum of in situ to microinvasive cancers. Twenty-eight dedicated breast pathologists assessed these cases at different magnifications through a web-based platform in two rounds: first HE only and after a washout period by both HE and IHC. Consistency in the recognition of microinvasion significantly improved with the use of IHC. Concordance rates increased from 0.85 to 0.96, kappa from 0.5 to 0.85, the number of cases with 100% agreement rose from 9/50 to 25/50 with IHC and the certainty of diagnosis also increased. The use of IHC markedly improves the consistency of identifying microinvasion. This corroborates previous recommendations to use IHC for myoepithelial markers to clarify cases where uncertainty exists about the presence of microinvasion. Microinvasive carcinoma is a rare entity, and seeking a second opinion may avoid overdiagnosis. PMID- 26818834 TI - The zinc-finger transcription factor SALL4 is frequently expressed in human cancers: association with clinical outcome in squamous cell carcinoma but not in adenocarcinoma of the esophagus. AB - SALL4 is a transcription factor originally identified as a homeotic gene essential for organ development. Early studies suggested that SALL4 is a useful marker to identify testicular and ovarian germ cell tumors. The aim of the study was to evaluate the diagnostic potential of SALL4 immunohistochemistry. Immunohistochemical staining was performed on a tissue microarray (TMA) with 3966 samples from 94 different tumor types and on a further TMA with 492 esophagus carcinomas. SALL4 immunostaining was by far most prevalent and most intensive in testicular tumors with a positivity rate of 93.1% in seminomas, 80% in mixed germ cell tumors (embryonic carcinomas/yolk sac tumors), and 18.5% in teratomas, respectively. However, SALL4 expression is not specific to germ cell tumors. We observed SALL4 positivity in non-germ cell tumors as carcinomas of the kidney (28.9% of chromophobe, 34.4% of clear cell carcinoma), in intestinal type adenocarcinoma of the stomach (10.9%), in adenocarcinoma (10.5%) and squamous cell carcinoma (7.2%) of the esophagus, and in malignant melanoma (8.1%) and invasive urothelial bladder carcinoma (20%). SALL4 expression was not found in lymphomas, in soft tissue tumors or breast tumors. At analysis of esophagus carcinoma TMA, no significant association was seen between SALL4 expression and overall survival in adenocarcinoma. However, SALL4 expression was strongly associated with worse overall survival in squamous cell carcinoma. SALL4 expression can be found at relevant frequencies in various tumors of different primary sites. SALL4 expression in squamous cell carcinoma of the esophagus may constitute a sign of dedifferentiation leading to poor patient prognosis. PMID- 26818835 TI - Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma. AB - Proliferative activity, assessed by Ki67 immunohistochemistry (IHC), is an established prognostic and predictive biomarker of breast cancer (BC). However, it remains under-utilized due to lack of standardized robust measurement methodologies and significant intratumor heterogeneity of expression. A recently proposed methodology for IHC biomarker assessment in whole slide images (WSI), based on systematic subsampling of tissue information extracted by digital image analysis (DIA) into hexagonal tiling arrays, enables computation of a comprehensive set of Ki67 indicators, including intratumor variability. In this study, the tiling methodology was applied to assess Ki67 expression in WSI of 152 surgically removed Ki67-stained (on full-face sections) BC specimens and to test which, if any, Ki67 indicators can predict overall survival (OS). Visual Ki67 IHC estimates and conventional clinico-pathologic parameters were also included in the study. Analysis revealed linearly independent intrinsic factors of the Ki67 IHC variance: proliferation (level of expression), disordered texture (entropy), tumor size and Nottingham Prognostic Index, bimodality, and correlation. All visual and DIA-generated indicators of the level of Ki67 expression provided significant cutoff values as single predictors of OS. However, only bimodality indicators (Ashman's D, in particular) were independent predictors of OS in the context of hormone receptor and HER2 status. From this, we conclude that spatial heterogeneity of proliferative tumor activity, measured by DIA of Ki67 IHC expression and analyzed by the hexagonal tiling approach, can serve as an independent prognostic indicator of OS in BC patients that outperforms the prognostic power of the level of proliferative activity. PMID- 26818836 TI - Protocol: Evaluating the impact of a nation-wide train-the-trainer educational initiative to enhance the quality of palliative care for children with cancer. AB - BACKGROUND: There are identified gaps in the care provided to children with cancer based on the self-identified lack of education for health care professionals in pediatric palliative care and in the perceptions of bereaved parents who describe suboptimal care. In order to address these gaps, we will implement and evaluate a national roll-out of Education in Palliative and End-of Life Care for Pediatrics (EPEC(r)-Pediatrics), using a 'Train-the-Trainer' model. METHODS/DESIGN: In this study we are using a pre- post-test design and an integrated knowledge translation approach to assess the impact of the educational roll-out in four areas: 1) self-assessed knowledge of health professionals; 2) knowledge dissemination outcomes; 3) practice change outcomes; and 4) quality of palliative care. The quality of palliative care will be assessed using data from three sources: a) parent and child surveys about symptoms, quality of life and care provided; b) health record reviews of deceased patients; and c) bereaved parent surveys about end-of-life and bereavement care. After being trained in EPEC(r)-Pediatrics, 'Master Facilitators' will train 'Regional Teams' affiliated with 16 pediatric oncology programs in Canada. Each team will consist of three to five health professionals representing oncology, palliative care, and the community. Each team member will complete online modules and attend one of two face-to-face conferences, where they will receive training and materials to teach the EPEC(r)-Pediatrics curriculum to 'End-Users' in their region. Regional Teams will also choose a Tailored Implementation of Practice Standards (TIPS) Kit to guide implementation of a quality improvement project in their region; support will be provided via quarterly meetings with Co-Leads and via a listserv and webinars with other teams. DISCUSSION: Through this study we aim to raise the level of pediatric palliative care education amongst health care professionals in Canada. Our study will be a significant step forward in evaluation of the impact of EPEC(r)-Pediatrics both on dissemination outcomes and on care quality at a national level. Based on the anticipated success of our project we hope to expand the EPEC(r)-Pediatrics roll-out to health professionals who care for children with non-oncological life-threatening conditions. PMID- 26818837 TI - Overexpression of HMGA2 promotes tongue cancer metastasis through EMT pathway. AB - BACKGROUND: Metastasis to long distance organs is the main reason leading to morality of tongue squamous cell carcinoma (TSCC); however, the molecular mechanisms are still unknown. High mobility group AT-hook 2 (HMGA2) is highly expressed in multiple metastatic carcinomas, in which it contributes to cancer progression, metastasis and poor prognosis by upregulating Snail expression and inducing epithelial mesenchymal transition (EMT). This study focuses on investigating the role and mechanism of regulation of HMGA2 in the metastasis of TSCC. METHODS: HMGA2 mRNA and protein expression were examined in TSCC specimens by quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry (IHC). Western blotting, IHC and immunofluorescence were also used to measure the expression and localization of EMT marker E-Cadherin and Vimentin both in TSCC cells and tissues. Knockdown assay was performed in vitro in TSCC cell lines using small interfering RNAs and the functional assay was carried out to determine the role of HMGA2 in TSCC cell migration and invasion. RESULTS: TSCC mRNA and protein expression were significantly up-regulated in tumor tissues when compared to adjacent non-tumor tissues, and the overexpression of HMGA2 was closely correlated with lymph nodes metastasis. Clinicopathological analysis indicated that HMGA2 expression was associated with clinical stage (P = 0.001), lymph node metastasis (P = 0.000), histological differentiation (P = 0.002) and survival (P = 0.000). Silencing the HMGA2 expression in Cal27 and UM1 resulted in the inhibition of cell migration and invasion, meanwhile down regulation of HMGA2 impaired the phenotype of EMT in TSCC cell lines and tissues. The Multivariate survival analysis indicates that HMGA2 can be an independent prognosis biomarker in TSCC. CONCLUSION: Our findings demonstrate that HMGA2 promotes TSCC invasion and metastasis; additionally, HMGA2 is an independent prognostic factor which implied that HMGA2 can be a biomarker both for prognosis and therapeutic target of TSCC. PMID- 26818838 TI - A Bayesian approach for estimating allele-specific expression from RNA-Seq data with diploid genomes. AB - BACKGROUND: RNA-sequencing (RNA-Seq) has become a popular tool for transcriptome profiling in mammals. However, accurate estimation of allele-specific expression (ASE) based on alignments of reads to the reference genome is challenging, because it contains only one allele on a mosaic haploid genome. Even with the information of diploid genome sequences, precise alignment of reads to the correct allele is difficult because of the high-similarity between the corresponding allele sequences. RESULTS: We propose a Bayesian approach to estimate ASE from RNA-Seq data with diploid genome sequences. In the statistical framework, the haploid choice is modeled as a hidden variable and estimated simultaneously with isoform expression levels by variational Bayesian inference. Through the simulation data analysis, we demonstrate the effectiveness of the proposed approach in terms of identifying ASE compared to the existing approach. We also show that our approach enables better quantification of isoform expression levels compared to the existing methods, TIGAR2, RSEM and Cufflinks. In the real data analysis of the human reference lymphoblastoid cell line GM12878, some autosomal genes were identified as ASE genes, and skewed paternal X chromosome inactivation in GM12878 was identified. CONCLUSIONS: The proposed method, called ASE-TIGAR, enables accurate estimation of gene expression from RNA Seq data in an allele-specific manner. Our results show the effectiveness of utilizing personal genomic information for accurate estimation of ASE. An implementation of our method is available at http://nagasakilab.csml.org/ase tigar . PMID- 26818839 TI - Stabilization of Live Attenuated Influenza Vaccines by Freeze Drying, Spray Drying, and Foam Drying. AB - PURPOSE: The goal of this research is to develop stable formulations for live attenuated influenza vaccines (LAIV) by employing the drying methods freeze drying, spray drying, and foam drying. METHODS: Formulated live attenuated Type-A H1N1 and B-strain influenza vaccines with a variety of excipient combinations were dried using one of the three drying methods. Process and storage stability at 4, 25 and 37 degrees C of the LAIV in these formulations was monitored using a TCID50 potency assay. Their immunogenicity was also evaluated in a ferret model. RESULTS: The thermal stability of H1N1 vaccine was significantly enhanced through application of unique formulation combinations and drying processes. Foam dried formulations were as much as an order of magnitude more stable than either spray dried or freeze dried formulations, while exhibiting low process loss and full retention of immunogenicity. Based on long-term stability data, foam dried formulations exhibited a shelf life at 4, 25 and 37 degrees C of >2, 1.5 years and 4.5 months, respectively. Foam dried LAIV Type-B manufactured using the same formulation and process parameters as H1N1 were imparted with a similar level of stability. CONCLUSION: Foam drying processing methods with appropriate selection of formulation components can produce an order of magnitude improvement in LAIV stability over other drying methods. PMID- 26818840 TI - The Influence of Stabilized Deconjugated Ursodeoxycholic Acid on Polymer-Hydrogel System of Transplantable NIT-1 Cells. AB - PURPOSE: The encapsulation of pancreatic beta-cells in biocompatible matrix has generated great interest in diabetes treatment. Our work has shown improved microcapsules when incorporating the bile acid ursodeoxycholic acid (UDCA), in terms of morphology and cell viability although cell survival remained low. Thus, the study aimed at incorporating the polyelectrolytes polyallylamine (PAA) and poly-l-ornithine (PLO), with the polymer sodium alginate (SA) and the hydrogel ultrasonic gel (USG) with UDCA and examined cell viability and functionality post microencapsulation. METHODS: Microcapsules without (control) and with UDCA (test) were produced using 1% PLO, 2.5% PAA, 1.8% SA and 4.5% USG. Pancreatic beta-cells were microencapsulated and the microcapsules' morphology, surface components, cellular and bile acid distribution, osmotic and mechanical stability as well as biocompatibilities, insulin production, bioenergetics and the inflammatory response were tested. RESULTS: Incorporation of UDCA at 4% into a PLO-PAA-SA formulation system increased cell survival (p < 0.01), insulin production (p < 0.01), reduced the inflammatory profile (TNF-alpha, IFN-Upsilon, IL-6 and IL 1beta; p < 0.01) and improved the microcapsule physical and mechanical strength (p < 0.01). CONCLUSIONS: beta-cell microencapsulation using 1% PLO, 2.5% PAA, 1.8% SA, 4.5% USG and the bile acid UDCA (4%) has good potential in cell transplantation and diabetes treatment. PMID- 26818841 TI - Distinguishing aggregate formation and aggregate clearance using cell-based assays. AB - The accumulation of ubiquitylated proteinaceous inclusions represents a complex process, reflecting the disequilibrium between aggregate formation and aggregate clearance. Although decreasing aggregate formation or augmenting aggregate clearance will ultimately lead to a diminished aggregate burden, in terms of disease pathogenesis, the different approaches can have distinct outcomes. Using a novel cell-based assay that can distinguish newly formed versus preformed inclusions, we demonstrate that two proteins previously implicated in the autophagic clearance of expanded polyglutamine inclusions, HspB7 and Alfy (also known as WDFY3), actually affect very distinct cellular processes to affect aggregate burden. Using this cell-based assay, we also establish that constitutive expression of the aggregation-prone protein can measurably slow the elimination of protein aggregates, given that not all aggregates appear to be available for degradation. This new assay can therefore not only determine at what step a modifier might influence aggregate burden, but also can be used to provide new insights into how protein aggregates are targeted for degradation. PMID- 26818843 TI - Checkpoint Inhibitors for the Treatment of Hodgkin Lymphoma. AB - Hodgkin lymphoma's (HL) tumor composition is characterized by a paucity of malignant cells and a preponderance of immune and stromal cells. Despite the rich immune milieu within the tumor microenvironment, malignant cells are able to effectively evade the immune system and use immune support to promote lymphoma cell growth and proliferation. Recognizing this has led to the identification of checkpoint inhibitory signals that enable immune evasion and to opening the door to therapeutic strategies on how to exploit the immune system in targeting tumor cells. We discuss herein some of the tumor evasion mechanisms in HL with a particular focus on the immune checkpoint pathways and focus on recent clinical data of checkpoint blockade in HL treatment. PMID- 26818842 TI - Force-dependent switch in protein unfolding pathways and transition-state movements. AB - Although it is known that single-domain proteins fold and unfold by parallel pathways, demonstration of this expectation has been difficult to establish in experiments. Unfolding rate, [Formula: see text], as a function of force f, obtained in single-molecule pulling experiments on src SH3 domain, exhibits upward curvature on a [Formula: see text] plot. Similar observations were reported for other proteins for the unfolding rate [Formula: see text]. These findings imply unfolding in these single-domain proteins involves a switch in the pathway as f or [Formula: see text] is increased from a low to a high value. We provide a unified theory demonstrating that if [Formula: see text] as a function of a perturbation (f or [Formula: see text]) exhibits upward curvature then the underlying energy landscape must be strongly multidimensional. Using molecular simulations we provide a structural basis for the switch in the pathways and dramatic shifts in the transition-state ensemble (TSE) in src SH3 domain as f is increased. We show that a single-point mutation shifts the upward curvature in [Formula: see text] to a lower force, thus establishing the malleability of the underlying folding landscape. Our theory, applicable to any perturbation that affects the free energy of the protein linearly, readily explains movement in the TSE in a beta-sandwich (I27) protein and single-chain monellin as the denaturant concentration is varied. We predict that in the force range accessible in laser optical tweezer experiments there should be a switch in the unfolding pathways in I27 or its mutants. PMID- 26818845 TI - Dynamic and static behavior of the H...pi and E...pi interactions in EH2 adducts of benzene pi-system (E = O, S, Se and Te), elucidated by QTAIM dual functional analysis. AB - Dynamic and static behavior of the interactions in the EH2 adducts of a benzene pi-system (E = O, S, Se and Te) is elucidated by applying QTAIM-DFA (QTAIM dual functional analysis). Two types of H-*-pi and E-*-pi interactions are detected in the adducts, where the asterisk (*) emphasizes the existence of the bond critical point (BCP) on the interaction in question. Total electron energy densities Hb(rc) are plotted versus Hb(rc) -Vb(rc)/2 [=(h(2)/8m)?(2)rhob(rc)] at BCPs in QTAIM-DFA, where Vb(rc) are the potential energy densities at BCPs. Data from the fully optimized structures are analyzed by polar (R, theta) coordinate representation. Each plot for an interaction, containing data from the perturbed structures with those of the fully optimized one, shows a specific curve, which provides important information. The plot is expressed by (thetap, kappap): thetap corresponds to the tangent line for the plot and kappap is the curvature. theta and thetap are measured from the y-axis and y-direction, respectively. Moreover, (R, theta) corresponds to the static nature, (thetap, kappap) represents the dynamic nature of interactions. While theta classifies the interaction in question, thetap characterizes it. Both values are less than 90 degrees for all H-*-pi and E-*-pi interactions examined in this study; therefore, they are all classified by the pure closed-shell interactions and predicted to have the character of vdW nature. However, it is suggested that E-*-pi has the nature of the stronger interaction than the case of H-*-pi for dynamic behavior in the same species evaluated at the MP2 and M06-2X levels. The nature of the interactions is well analyzed and specified by applying QTAIM-DFA. PMID- 26818844 TI - SCF(Cyclin F)-dependent degradation of CDC6 suppresses DNA re-replication. AB - Maintenance of genome stability requires that DNA is replicated precisely once per cell cycle. This is believed to be achieved by limiting replication origin licensing and thereby restricting the firing of each replication origin to once per cell cycle. CDC6 is essential for eukaryotic replication origin licensing, however, it is poorly understood how CDC6 activity is constrained in higher eukaryotes. Here we report that the SCF(Cyclin F) ubiquitin ligase complex prevents DNA re-replication by targeting CDC6 for proteasomal degradation late in the cell cycle. We show that CDC6 and Cyclin F interact through defined sequence motifs that promote CDC6 ubiquitylation and degradation. Absence of Cyclin F or expression of a stable mutant of CDC6 promotes re-replication and genome instability in cells lacking the CDT1 inhibitor Geminin. Together, our work reveals a novel SCF(Cyclin F)-mediated mechanism required for precise once per cell cycle replication. PMID- 26818846 TI - Expression of prokineticin 2 and its receptor in the macaque monkey brain. AB - Prokineticin 2 (PK2) has been indicated as an output signaling molecule for the suprachiasmatic nucleus (SCN) circadian clock. Most of these studies were performed with nocturnal animals, particularly mice and rats. In the current study, the PK2 and its receptor, PKR2, was cloned from a species of diurnal macaque monkey. The macaque monkey PK2 and PKR2 were found to be highly homologous to that of other mammalian species. The mRNA expression of PK2 and PKR2 in the macaque brain was examined by in situ hybridization. The expression patterns of PK2 and PKR2 in the macaque brain were found to be quite similar to that of the mouse brain. Particularly, PK2 mRNA was shown to oscillate in the SCN of the macaque brain in the same phase and with similar amplitude with that of nocturnal mouse brain. PKR2 expression was also detected in known primary SCN targets, including the midline thalamic and hypothalamic nuclei. In addition, we detected the expression of PKR2 mRNA in the dorsal raphe nucleus (DR) of both macaque and mouse brains. As a likely SCN to dorsal raphe projection has previously been indicated, the expression of PKR2 in the raphe nuclei of both macaque and mouse brain signifies a possible role of DR as a previously unrecognized primary SCN projection target. PMID- 26818847 TI - Effects on mobility training and de-adaptations in subjects with Spinal Cord Injury due to a Wearable Robot: a preliminary report. AB - BACKGROUND: Spinal cord injury (SCI) is a severe neurological disorder associated not only with ongoing medical complications but also with a significant loss of mobility and participation. The introduction of robotic technologies to recover lower limb function has been greatly employed in the rehabilitative practice. The aim of this preliminary report were to evaluate the efficacy, the feasibility and the changes in the mobility and in the de-adaptations of a new rehabilitative protocol for EKSOTM a robotic exoskeleton device in subjects with SCI disease with an impairment of lower limbs assessed by gait analysis and clinical outcomes. METHOD: This is a pilot single case experimental A-B (pre-post) design study. Three cognitively intact voluntary participants with SCI and gait disorders were admitted. All subjects were submitted to a training program of robot walking sessions for 45 min daily over 20 sessions. The spatiotemporal parameters at the beginning (T0) and at the end of treatment (T1) were recorded. Other clinical assessments (6 min walking test and Timed Up and Go test) were acquired at T0 and T1. RESULTS: Robot training were feasible and acceptable and all participants completed the training sessions. All subjects showed improvements in gait spatiotemporal indexes (Mean velocity, Cadence, Step length and Step width) and in 6 min Walking Test (T0 versus T1). CONCLUSIONS: Robot training is a feasible form of rehabilitation for people with SCI. Further investigation regarding long term effectiveness of robot training in time is necessary. TRIAL REGISTRATION: ClinicalTrials.gov NCT02065830. PMID- 26818848 TI - Learning a hierarchical representation of the yeast transcriptomic machinery using an autoencoder model. AB - BACKGROUND: A living cell has a complex, hierarchically organized signaling system that encodes and assimilates diverse environmental and intracellular signals, and it further transmits signals that control cellular responses, including a tightly controlled transcriptional program. An important and yet challenging task in systems biology is to reconstruct cellular signaling system in a data-driven manner. In this study, we investigate the utility of deep hierarchical neural networks in learning and representing the hierarchical organization of yeast transcriptomic machinery. RESULTS: We have designed a sparse autoencoder model consisting of a layer of observed variables and four layers of hidden variables. We applied the model to over a thousand of yeast microarrays to learn the encoding system of yeast transcriptomic machinery. After model selection, we evaluated whether the trained models captured biologically sensible information. We show that the latent variables in the first hidden layer correctly captured the signals of yeast transcription factors (TFs), obtaining a close to one-to-one mapping between latent variables and TFs. We further show that genes regulated by latent variables at higher hidden layers are often involved in a common biological process, and the hierarchical relationships between latent variables conform to existing knowledge. Finally, we show that information captured by the latent variables provide more abstract and concise representations of each microarray, enabling the identification of better separated clusters in comparison to gene-based representation. CONCLUSIONS: Contemporary deep hierarchical latent variable models, such as the autoencoder, can be used to partially recover the organization of transcriptomic machinery. PMID- 26818849 TI - Longitudinal Strain and Strain Rate Abnormalities Precede Invasive Diagnosis of Transplant Coronary Artery Vasculopathy in Pediatric Cardiac Transplant Patients. AB - Transplant coronary artery vasculopathy (TCAV) is the primary cause of late graft loss in pediatric heart transplant recipients. TCAV is diagnosed using angiography or intravascular ultrasound; however, noninvasive methods remain elusive. We sought to define patterns of myocardial mechanics in patients with TCAV and to determine whether this can detect TCAV before invasive methods. In this retrospective study, we queried our heart transplant database to identify all recipients with TCAV since 2006 (n = 41). Echoes were reviewed from the last normal catheterization and at TCAV diagnosis, and from time-matched transplant controls (n = 33) without TCAV. Peak global circumferential and longitudinal strain and systolic and diastolic strain rate (SSR and DSR) of the left ventricle were derived using velocity vector imaging. T tests were used to compare both groups longitudinally and between groups at both time points. Longitudinal strain, SSR, and DSR were diminished in the TCAV group compared to the transplant control group at both time points. No differences were found across time points in either group. Retrospective modeling using a longitudinal strain cutoff of 15 % on echoes 2 years prior to TCAV diagnosis predicted development or exclusion of TCAV with sensitivity of 53 %, specificity of 89 % with an area under the curve of 0.8. Decreases in longitudinal strain measurements demonstrate that alterations in myocardial mechanics occur in patients with TCAV at least 2 years prior to invasive diagnosis. These early changes may be due to microvascular disease. This modality could aid in earlier treatment and intervention for this challenging problem . PMID- 26818850 TI - Safety and Efficacy of Prophylactic Amiodarone in Preventing Early Junctional Ectopic Tachycardia (JET) in Children After Cardiac Surgery and Determination of Its Risk Factor. AB - Postoperative arrhythmia is a common complication after open heart surgery in children. JET is the most common and dangerous arrhythmia. We aimed to assess safety and efficacy of prophylactic amiodarone in preventing JET in children underwent cardiac surgery and to assess risk factors for JET among our patients. In total, 117 children who underwent cardiac surgery for CHD at Tanta University Hospital from October 2011 to April 2015 were divided in two groups; amiodarone group (65 patients) was given prophylactic amiodarone intraoperatively and placebo group (52 patients). Amiodarone is started as loading dose of 5 mg/kg IV in the operating room after induction of anesthesia and continued for 3 days as continuous infusion 10-15 MUg/kg/min. Primary outcome and secondary outcomes of amiodarone administration were reported. We studied pre-, intra- and postoperative factors to determine risk factors for occurrence of JET among these children. Prophylactic amiodarone was found to significantly decrease incidence of postoperative JET from 28.9 % in placebo group to 9.2 % in amiodarone group, and symptomatic JET from 11.5 % in placebo group to 3.1 % in amiodarone group, and shorten postoperative intensive care unit and hospital stay without significant side effects. Risk factors for occurrence of JET were younger age, lower body weight, longer cardiopulmonary bypass, aortic cross-clamp time, hypokalemia, hypomagnesemia, acidosis and high dose of inotropes. JET was more associated with surgical repair of right ventricular outlet obstruction as in case of tetralogy of Fallot and pulmonary stenosis. Most of JET 15/21 (71.4 %) occurred in the first day postoperatively, and 6/21 occurred in the second day (28.6 %). Prophylactic amiodarone is safe and effective in preventing early JET in children after open heart surgery. PMID- 26818852 TI - Shape matters when engineering mesoporous silica-based nanomedicines. AB - Mesoporous silica nanomaterials have been successfully employed in the development of novel carriers for drug delivery. Numerous studies have been reported on engineering mesoporous silica-based carriers for drug loading, release, cellular uptake, and biocompatibility. A number of design parameters that govern the in vitro and in vivo performance of the carriers, including particle diameter, surface chemistry, and pore size, have been tuned to optimize nanomedicine efficacy. However, particle shape, which may generate a high impact on nanomedicine performance, has still not been thoroughly investigated. This is probably due to the limited availability of strategies and techniques to produce non-spherical mesoporous silica nanomaterials. Recent breakthroughs in controlling the particle shape of mesoporous silica nanomaterials have confirmed the important roles of shape on nanomedicine development. This review article introduces various fabrication methods for non-spherical mesoporous silica nanomaterials, including rod, ellipsoid, film, platelet/sheet, and cube, and the roles of particle shape in nanomedicine applications. PMID- 26818851 TI - Co-morbidity in patients with early rheumatoid arthritis - inflammation matters. AB - BACKGROUND: Patients with rheumatoid arthritis (RA) suffer from co-morbidities that contribute to a shortened lifespan. Inflammation is important for the development of cardiovascular disease, but little is known on its relationship with other co-morbidities. We investigated the role of inflammation for the development of new comorbidities in early RA. METHODS: Since 1995, all patients with early RA in Northern Sweden are included in a prospective study on co morbidities, with a total of 950 patients being included. At the time for this study, 726 had been ill for >=5 years. Data on co-morbidities, clinical and laboratory disease activity and pharmacological therapy were collected from patient records and further validated using a questionnaire at RA onset (T0) and after 5 years (T5). RESULTS: Of the patients, 53.2 % of the patients had one or more co-morbidity at onset, the commonest being: hypertension (27.3 %), obstructive pulmonary disease (13.9 %), diabetes (8.0 %), hypothyroidism (6.3 %) and malignancy (5.0 %). After 5 years, 41.0 % had developed at least one new co morbidity, the most common being: hypertension (15.1 %), malignancy (7.6 %), stroke/transient ischemic accident (5.1 %), myocardial infarction (4.3 %) and osteoporosis (3.7 %). Age at disease onset, a raised erythrocyte sedimentation rate (ESR) at inclusion, previous treatment with glucocorticoids (GC; p < 0.001 for all), extra-articular RA (Ex-RA; p < 0.01), DAS28 (area under the curve) at 24 months (p < 0.05), previous smoking at inclusion (p = 0.058) and male gender (p < 0.01) were associated with a new co-morbidity overall at T5. Treatment with biologics (p < 0.05) reduced the risk. In multiple logistic regression modelling, ESR (p = 0.036) at inclusion was associated with a new co-morbidity after 5 years, adjusted for age, sex, smoking and GC treatment. In a similar model, Ex-RA (p < 0.05) was associated with a new co-morbidity at T5. In a third model, adjusted for age and sex, a new pulmonary co-morbidity was associated with a smoking history at inclusion (p < 0.01), but not with ESR. CONCLUSION: There was substantial co-morbidity among early RA patients already at disease onset, with considerable new co-morbidity being added during the first five years. Measures of disease activity were associated with the occurrence of a new co-morbidity indicating that the inflammation is of importance in this context. PMID- 26818853 TI - Tetrapod V1R-like ora genes in an early-diverging ray-finned fish species: the canonical six ora gene repertoire of teleost fish resulted from gene loss in a larger ancestral repertoire. AB - BACKGROUND: Chemical senses serve a multitude of essential functions across the animal kingdom. Vertebrates employ four GPCR families to detect odors, among them the v1r/ora gene family. The V1R family is known to evolve rapidly in the lobe finned lineage giving rise to tetrapods, but the homologous ORA family consists of just six highly conserved genes in teleost fish, with direct orthologs in the lobe-finned fish coelacanth. Thus, the teleost repertoire of six canonical ora genes was assumed to be the ancestral feature before the divergence of ray-finned and lobe-finned fish. So far, this hypothesis has not been tested with earlier diverging ray-finned fish. RESULTS: We have newly identified the complete ora gene repertoires of five teleost species, and of spotted gar, a basal ray-finned fish, using thorough data mining and extensive phylogenetic analysis. The genomes of eight further teleost species were re-analyzed for their ORA repertoires. We report that direct orthologs of the six canonical ora genes (ora1-6) were present in all newly analyzed species, with faithfully preserved exon/intron structure and mostly preserved genomic arrangement in symmetric pairs for ora1-4. In four teleost species including medaka and cave fish we observe species-specific gene duplication events. Thus, the ora gene repertoire in teleost fish is not quite as strictly conserved as previously assumed. In fact, the examination of non synonymous vs. synonymous substitution rates (dN/dS) shows pronounced negative selection in five of the six ora genes, but also rare occurrence of positive selection in ora3 and ora6. Surprisingly, spotted gar possesses beyond the six canonical genes three additional genes, ora7-8b, orthologous to coelacanth genes v1r07-10. No orthologs for these genes were found in teleosts and cartilaginous fish. CONCLUSIONS: Early diverging ray-finned fish such as the spotted gar possess several v1r-like genes previously assumed to be restricted to the lobe finned lineage, but now found to be already present in the most recent common ancestor of lobe- and ray-finned fish. Thus, the presence of just six canonical ora genes in many teleost species is not the ancestral feature of the ray-finned lineage, but caused by loss of two ancestral genes in teleosts. PMID- 26818855 TI - K2 killer toxin-induced physiological changes in the yeast Saccharomyces cerevisiae. AB - Saccharomyces cerevisiae cells produce killer toxins, such as K1, K2 and K28, that can modulate the growth of other yeasts giving advantage for the killer strains. Here we focused on the physiological changes induced by K2 toxin on a non-toxin-producing yeast strain as well as K1, K2 and K28 killer strains. Potentiometric measurements were adjusted to observe that K2 toxin immediately acts on the sensitive cells leading to membrane permeability. This correlated with reduced respiration activity, lowered intracellular ATP content and decrease in cell viability. However, we did not detect any significant ATP leakage from the cells treated by killer toxin K2. Strains producing heterologous toxins K1 and K28 were less sensitive to K2 than the non-toxin producing one suggesting partial cross-protection between the different killer systems. This phenomenon may be connected to the observed differences in respiratory activities of the killer strains and the non-toxin-producing strain at low pH. This might also have practical consequences in wine industry; both as beneficial ones in controlling contaminating yeasts and non-beneficial ones causing sluggish fermentation. PMID- 26818854 TI - Replacement of the initial steps of ethanol metabolism in Saccharomyces cerevisiae by ATP-independent acetylating acetaldehyde dehydrogenase. AB - In Saccharomyces cerevisiae ethanol dissimilation is initiated by its oxidation and activation to cytosolic acetyl-CoA. The associated consumption of ATP strongly limits yields of biomass and acetyl-CoA-derived products. Here, we explore the implementation of an ATP-independent pathway for acetyl-CoA synthesis from ethanol that, in theory, enables biomass yield on ethanol that is up to 40% higher. To this end, all native yeast acetaldehyde dehydrogenases (ALDs) were replaced by heterologous acetylating acetaldehyde dehydrogenase (A-ALD). Engineered Ald(-) strains expressing different A-ALDs did not immediately grow on ethanol, but serial transfer in ethanol-grown batch cultures yielded growth rates of up to 70% of the wild-type value. Mutations in ACS1 were identified in all independently evolved strains and deletion of ACS1 enabled slow growth of non evolved Ald(-) A-ALD strains on ethanol. Acquired mutations in A-ALD genes improved affinity-Vmax/Km for acetaldehyde. One of five evolved strains showed a significant 5% increase of its biomass yield in ethanol-limited chemostat cultures. Increased production of acetaldehyde and other by-products was identified as possible cause for lower than theoretically predicted biomass yields. This study proves that the native yeast pathway for conversion of ethanol to acetyl-CoA can be replaced by an engineered pathway with the potential to improve biomass and product yields. PMID- 26818856 TI - Editorial: Retrospectives - lives behind the science. PMID- 26818858 TI - The Recent Development of alpha7 Nicotinic Acetylcholine Receptor (nAChR) Ligands as Therapeutic Candidates for the Treatment of Central Nervous System (CNS) Diseases. AB - Homomeric alpha7 nicotinic acetylcholine receptors (nAChRs) are implicated in the regulation of cognitive processes such as memory and attention and have potential as therapeutic targets for the treatment of the cognitive deficits associated with schizophrenia. Though numerous alpha7 nAChR agonists have been developed, and several have progressed to clinical trials, these are derived from few common chemotypes. Consequently, many of these alpha7 nAChR clinical candidates share unfavorable side-effect profile. SEN12333 represents a novel chemotype for the development of alpha7 nAChR agonists, and exploration of this scaffold has produced structurally diverse ligands with promising pharmacological properties. This review will summarize structure-affinity and -activity relationships surrounding analogs of SEN12333. PMID- 26818857 TI - Cholinergic Targets in Lung Cancer. AB - Lung cancers express an autocrine cholinergic loop in which secreted acetylcholine can stimulate tumor growth through both nicotinic and muscarinic receptors. Because activation of mAChR and nAChR stimulates growth; tumor growth can be stimulated by both locally synthesized acetylcholine as well as acetylcholine from distal sources and from nicotine in the high percentage of lung cancer patients who are smokers. The stimulation of lung cancer growth by cholinergic agonists offers many potential new targets for lung cancer therapy. Cholinergic signaling can be targeted at the level of choline transport; acetylcholine synthesis, secretion and degradation; and nicotinic and muscarinic receptors. In addition, the newly describe family of ly-6 allosteric modulators of nicotinic signaling such as lynx1 and lynx2 offers yet another new approach to novel lung cancer therapeutics. Each of these targets has their potential advantages and disadvantages for the development of new lung cancer therapies which are discussed in this review. PMID- 26818859 TI - The Cholinergic System: An Emerging Drug Target for Schizophrenia. AB - BACKGROUND: Cognitive deficits are amongst the most socially debilitating and least effectively treated symptoms of schizophrenia. The cholinergic system is a promising target for the design of novel drugs that can more effectively treat these symptoms. METHODS: We review the literature supporting the dysfunction of the cholinergic system in schizophrenia, discuss the preclinical and clinical data showing that modulating the cholinergic system could improve the symptoms of schizophrenia and review the main pharmacological strategies being investigated to treat cholinergic dysfunction in schizophrenia. RESULTS: Post-mortem and neuroimaging studies suggest there are widespread reductions in cholinergic receptor signalling in the cortex as well as subcortical regions, such as the hippocampus and striatum, in individuals with schizophrenia. Potential cholinergic drug targets are being pursued to increase receptor function. These include inhibiting the activity of the enzyme acetylcholinesterase to increase synaptic acetylcholine levels, and increasing the nicotinic receptor and muscarinic receptor activity with agonists or positive allosteric modulators. CONCLUSION: Amongst the most promising drug targets for treating schizophrenia are the alpha7 nicotinic receptor and the CHRM1 and CHRM4 muscarinic receptors. The recent development of allosteric modulators that selectively target these receptors offers the potential to more effectively treat the symptoms of schizophrenia. PMID- 26818861 TI - Serotonergic and Cholinergic Strategies as Potential Targets for the Treatment of Schizophrenia. AB - Currently availably antipsychotic drugs are effective in ameliorating the positive symptoms of schizophrenia. Nevertheless, the cognitive impairments and negative symptoms experienced by schizophrenia patients still await effective treatment. In particular, potential cognitive enhancers have received considerable attention in the field of schizophrenia research. From among the multiple therapeutic approaches that have recently been proposed, this review will focus on serotonin receptors, namely 5-HT5ARs, 5-HT6Rs and 5-HT7Rs, and on alpha 7 nicotinic acetylcholine receptors (alpha7-nAChRs). The purpose of this review is to summarise existing data regarding the effects of ligands of these receptors on measures of schizophrenia-like behaviours in animal models, with particular emphasis on their procognitive effects. Existing clinical data will also be reported, and the potential clinical efficacy of these compounds will be discussed with regard to the preclinical results. Possible explanations for the lack of clinically validated evidence and for the discrepancies between the clinical and preclinical data will also be provided. PMID- 26818862 TI - Targeting the Cholinergic System for Neuroprotection and/or Enhancement of Functional Recovery Following Neurotrauma. AB - Development of novel pharmacotherapies for the treatment of traumatic injury to the nervous system has been ongoing for over 40 years. Despite many promising compounds discovered using animal models, no treatments have successfully translated into the clinic. The central dogma in this field is that brain trauma initiates a complex chain of biochemical events leading to secondary brain damage and sustained neurological deficits. The delayed secondary brain injury is likely to result from multiple insults including oxidative stress, mitochondrial dysfunction, breakdown of the blood brain barrier, dysregulated release of glutamate, pro-inflammatory cytokines, and other mediators. However, therapies targeting these systems have generally met with failure in clinical trials. The purpose of this review is to summarize the models used for preclinical neurotrauma research, provide a brief overview of previous failed clinical trials in head and spinal cord injury, and finally, to review involvement of the cholinergic system and discuss implications for future research. Possibilities and pitfalls of targeting the cholinergic system for neuroprotection and/or enhancement of functional recovery are also discussed. PMID- 26818860 TI - Targeting Functional Biomarkers in Schizophrenia with Neuroimaging. AB - Many of the most debilitating symptoms for psychiatric disorders such as schizophrenia remain poorly treated. As such, the development of novel treatments is urgently needed. Unfortunately, the costs associated with high failure rates for investigational compounds as they enter clinical trials has led to pharmaceutical companies downsizing or eliminating research programs needed to develop these drugs. One way of increasing the probability of success for investigational compounds is to incorporate alternative methods of identifying biological targets in order to more effectively screen new drugs. A promising method of accomplishing this goal for psychiatric drugs is to use functional magnetic resonance imaging (fMRI). fMRI investigates neural circuits, shedding light on the biology that generates symptoms such as hallucinations. Once identified, relevant neural circuits can be targeted with pharmacologic interventions and the response to these drugs measured with fMRI. This review describes the early use of fMRI in this context, and discusses the alpha7 nicotinic receptor agonist 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A), as an example of the potential value of fMRI for psychiatric drug development. PMID- 26818863 TI - Serotonergic Drugs: Agonists/Antagonists at Specific Serotonergic Subreceptors for the Treatment of Cognitive, Depressant and Psychotic Symptoms in Alzheimer's Disease. AB - BACKGROUND: Alzheimer's disease is a neurodegenerative disease showing alterations in classical neurotransmitters, above all in the hippocampus and prefrontal/temporal cortices. In this disease, acetylcholine shows hypoactivity, noradrenaline first shows hyperactivity, and during the course of the disease an increasing hypoactivity, glutamate shows hyperactivity and excitotoxicity and GABA shows hypoactivity. In post-mortem studies, serotonin levels and the number of specific serotonergic subreceptors, for example 5-HT1B receptors, decreased. METHODS: We summarized the alterations of classical neurotransmitters in the brain regions involved in cognitive, depressive and psychotic symptoms in Alzheimer's disease. Starting from these neurotransmitter alterations, we describe neural networks including specific serotonergic subreceptors in the involved brain regions. RESULTS: In the hippocampus and prefrontal cortex, serotonin levels are associated with cognitive functions, whereas in the brainstem serotonin levels are related with affective symptoms. Psychotic symptoms which can occur in patients with Alzheimer's disease are associated with dopamine and serotonin hyperactivity in the mesolimbic system and hippocampus. The interaction between classical neurotransmitters and their specific subreceptors is shown in different brain areas. CONCLUSION: In clinical trials, the therapeutic effects of 5-HT4, 5-HT7 agonists and 5-HT3, 5-HT6 antagonists have been examined to improve cognitive symptoms in Alzheimer's disease. In these trials, 5-HT4 agonists and 5-HT4 antagonists showed a significant better effect in improving cognitive functions than placebo. The effect of such drugs on the formation of amyloid plaques is also examined. The appropriate use of antidepressant and antipsychotic drugs with an agonism or antagonism at specific serotonergic subreceptors is pointed out. Serotonin-selective antidepressant drugs significantly improve depressant symptoms and daily activities in Alzheimer patients and they are used to treat aggressive behaviour. Among the second generations antipsychotic drugs (D2 and 5-HT2A antagonists), drugs with a favorable metabolic profile should be used. PMID- 26818865 TI - The Role of alpha7 Nicotinic Acetylcholine Receptors and alpha7-Specific Antibodies in Neuroinflammation Related to Alzheimer Disease. AB - BACKGROUND: Alzheimer disease (AD) is a neurodegenerative disorder occurring in elderly people and leading to the loss of memory, practical and speaking habits. In spite of extensive efforts undertaken during the last decades, there is still no generally recognized explanation of the origin and primary pathological changes leading to AD development. Consequently, the suggested pharmacological approaches to treat the AD patients are mostly symptomatic and do not stop the disease progression. Neuroinflammation and cholinergic deficit usually accompany AD development. However, their impact in AD progression still waits for being properly recognized. OBJECTIVE: The present review aims at analysis of the role of inflammation and nicotinic acetylcholine receptors, primarily of alpha7 subtype (alpha7 nAChRs), in the development of AD in humans and AD-like symptoms in experimental animals. RESULTS: The reviewed data describe the involvement of alpha7 nAChRs in the AD pathogenesis, in particular, through their interaction with amyloid-beta, maintenance of brain cell viability and regulation of neuroinflammation. They also delineate the role of alpha7-specific (auto)antibodies in stimulating neuroinflammation, memory impairment in mice and AD progression in humans. CONCLUSION: Neuroinflammation is suggested as a primary stimulus sufficient to trigger accumulation of pathologically processed amyloid beta, degeneration of cholinergic neurons and memory impairment. The level of alpha7 nAChR expression in the brain is critical for supporting the resistance to inflammatory and apoptogenic agents. The data presented may be a basis to create a new strategy for preventing and, possibly, slowing AD development in humans. PMID- 26818864 TI - Desformylflustrabromine: A Novel Positive Allosteric Modulator for beta2 Subunit Containing Nicotinic Receptor Sub-Types. AB - Nicotinic acetylcholine receptors are ligand-gated transmembrane ion channels that are present at the neuromuscular junction and in different locations in the nervous system. The different subtypes of neuronal nicotinic acetylcholine receptors that are found in the brain are thought to be involved in many neurological processes such as pain, cognitive function and depression, as well as in the pathophysiology of numerous neurological diseases and conditions. While the neurotransmitter acetylcholine is an endogenous agonist for all nicotinic receptors subtypes, many drugs that act as agonists and antagonists have also been identified or developed for these receptors. In addition, a novel class of compounds described as allosteric modulators have also been identified or developed for nicotinic acetylcholine receptors. Allosteric modulators are ligands that bind to nicotinic receptors at sites other than the orthosteric site where acetylcholine binds. One such allosteric modulator is desformylflustrabromine. Five chemical analogs along with desformylflustrabromine act as positive allosteric modulator for nAChRs that contain the beta2 subunit in their pentameric structure. Here the discovery and development, medicinal chemistry and pharmacological actions of desformylflustrabromine have been discussed. Desformylflustrabromine and its chemical analogs have the potential to develop into clinically used drugs for neurological diseases and conditions where nicotinic acetylcholine receptors are involved. PMID- 26818866 TI - Nicotinic Acetylcholine Receptors in the Pathophysiology of Al zheimer's Disease: The Role of Protein-Protein Interactions in Current and Future Treatment. AB - Nicotinic acetylcholine receptors (nAChRs) have been pursued for decades as potential molecular targets to treat cognitive dysfunction in Alzheimer's disease (AD) due to their positioning within regions of the brain critical in learning and memory, such as the prefrontal cortex and hippocampus, and their demonstrated role in processes underlying cognition such as synaptic facilitation, and theta and gamma wave activity. Historically, activity at these receptors is facilitated in AD by use of drugs that increase the levels of their endogenous agonist acetylcholine, and more recently nAChR selective ligands have undergone clinical trials. Here we discuss recent findings suggesting that the expression and function of nAChRs in AD may be regulated by direct interactions with specific proteins, including Lynx proteins, NMDA-receptors and the Wnt/beta-catenin pathway, as well as beta-amyloid. The ability of protein interactions to modify nAChR function adds a new level of complexity to cholinergic signaling in the brain that may be specifically altered in AD. It is currently not known to what degree current nAChR ligands affect these interactions, and it is possible that the difference in the clinical effect of nAChR ligands in AD is related to differences in their ability to modulate nAChR protein interactions, rather than their effects on ion flow through the receptors. Drugs designed to target these interactions may thus provide a new avenue for drug development to ameliorate cognitive symptoms in AD. Notably, the development of experimental drugs that specifically modulate these interactions may provide the opportunity to selectively affect those aspects of nAChR function that are affected in AD. PMID- 26818867 TI - Role of Nicotinic and Muscarinic Receptors on Synaptic Plasticity and Neurological Diseases. AB - The cholinergic activity in the brain is fundamental for cognitive functions. The modulatory activity of the neurotransmitter acetylcholine (ACh) is mediated by activating a variety of nicotinic acetylcholine receptors (nAChR) and muscarinic acetylcholine receptors (mAChR). Accumulating evidence indicates that both nAChR and mAChRs can modulate the release of several other neurotransmitters, modify the threshold of long-term plasticity, finally improving learning and memory processes. Importantly, the expression, distribution, and/or function of these systems are altered in several neurological diseases. The aim of this review is to discuss our current knowledge on cholinergic receptors and their regulating synaptic functions and neuronal network activities as well as their use as targets for the development of new and clinically useful cholinergic ligands. These new therapies involve the development of novel and more selective cholinergic agonists and allosteric modulators as well as selective cholinesterase inhibitors, which may improve cognitive and behavioral symptoms, and also provide neuroprotection in several brain diseases. The review will focus on two nAChR receptor subtypes found in the mammalian brain and the most commonly targeted in drug discovery programs for neuropsychiatric disorder, the ligands of alpha4beta2 nAChR and alpha7 nAChRs. PMID- 26818868 TI - Regulation of Gait and Balance: The Underappreciated Role of Neuronal Nicotinic Receptor Agonists. AB - Alterations in gait and balance are manifest in numerous neurological disorders such as the ataxias and Parkinson's disease, and may occur as a consequence of stroke, traumatic brain injury and chemical insults to the brain. Although the underlying etiology of these disorders differs, disturbances in gait and balance appear to reflect deficits in cholinergic pathways within the brain. During the past 40 years, both clinical case studies and preclinical data have provided evidence that nicotinic cholinergic activation is beneficial for alleviating gait and balance deficits in many disorders. Further, studies indicate that activation of neuronal nicotinic receptors leads to neuroprotective and neurotrophic actions. And yet, despite these findings, there hsas been no concerted effort to develop neuronal nicotinic agonists for the treatment of abnormal gait and balance. The goal of this review is to shed light on the therapeutic benefit of the cholinergic nicotinic system for the treatment of ataxia, and discuss the challenges and limitations associated with developing drugs to treat disorders involving deficits in gait and balance. PMID- 26818869 TI - The Cholinergic Potential, the Vagus Nerve and Challenges in Treatment of Traumatic Brain Injury. AB - Existing treatments of traumatic brain injury (TBI) have failed to reverse tremendous losses in productivity, independence and overall quality of life among TBI victims and therefore, cannot be viewed as sufficient. Although there is no shortage of promising basic concepts that may translate to efficacious therapies after TBI, the accumulated knowledge has yet to deliver treatments that adequately meet clinical and social demands. In this article, we discuss novel concepts, recent advances and accompanying challenges in developing cholinergic and related therapies after TBI. PMID- 26818870 TI - Obstacles and Opportunities for Cholinergic Drug Development in the Treatment of Cognitive Disorders. AB - The frequency of neuropsychiatric disorders is greater than that of cancer, cardiovascular disease, and diabetes combined, and is growing at a faster rate than any other ailments in the United States or Europe. Despite a considerable need for the development of treatments for central nervous system disorders, pharmaceutical companies continue to reduce investment in this area of research. Of particular concern is the treatment of diseases and disorders that affect cognitive function, which are often given a lower priority for research investment than life threatening conditions or those with overt physical symptoms. Several reasons exist for this reduced investment, including a poor understanding of the mechanisms underlying impaired cognitive function, costly and long periods of development for these medications, disproportionately lower success rates, and a stigma associated with the medical treatment of mental illness. This paper will discuss these issues, review some of the successes resulting from research investment and discuss opportunities that should encourage increased research investment in cognitive disorders and their treatment. PMID- 26818871 TI - Opportunities and Challenges for Host-Directed Therapies in Tuberculosis. AB - BACKGROUND: Tuberculosis (TB) ranks alongside the human immunodeficiency virus (HIV) as cause of death due to an infectious disease. Recently, host-targeted therapies (HDT) have gained attention as a means to shorten the course of treatment of drug-sensitive TB, improve treatment outcomes of drug-resistant TB and generally improve the efficacy and preserve or restore lung architecture of TB patients. It has been suggested that supplementing anti-TB therapy with host response modulators will augment standard TB treatment by overcoming antibiotic resistance in pathogenic strains of Mycobacterium tuberculosis (Mtb) and related species, thus aiding in killing non-replicating bacilli. METHODS: The aim of this review is to examine pulmonary delivery strategies that can enhance the safety as well as efficacy of HDT against pulmonary TB. We reviewed literature in the public domain and revisited our own results on inhaled HDT to arrive at broad conclusions. RESULTS: HDT can be viewed as a strategy to evoke one or more of the following macrophage responses: (i) soluble, intracellular factors such as free radicals and antimicrobial peptides; (ii) soluble extracellular signals like cytokines, chemokines, prostaglandins, lipids, etc.; (iii) organelles and assemblies such as phagolysosomes or the inflammasome; (iv) Autophagy, via mTOR/S6 Kinase; and (v) apoptosis via caspases, bcr/abl products, etc. All of these may be optimally addressed using drugs approved for other uses. CONCLUSION: Deployment of HDT in TB may be optimally achieved through macrophage-targeted inhaled delivery systems. PMID- 26818872 TI - Dry Powder form of Polymeric Nanoparticles for Pulmonary Drug Delivery. AB - Delivery to the lungs is an efficient way to deliver drugs directly to the site of action or to the blood circulation. Because of limitations of direct administration of free drugs, particulate drug delivery systems such as DPI formulations based on nanoparticles (NPs) have been of interest for pulmonary drug delivery. The prolonged residence of NPs in the lungs due to ability to escape from the clearance mechanisms such as mucociliary escalator, macrophage uptake (a size of 1-2 um is ideal for macrophage phagocytosis), and translocation to the systemic circulation is amongst the key advantages of NPs. By this approach, the controlled pulmonary delivery of drugs, peptides, proteins, genes, siRNA, and vaccines is possible. Both natural (albumin, gelatin, alginate, collagen, cyclodextrin, and chitosan) and synthetic (poly (lactide-co-glycolide) (PLGA), polyacrylates and polyanhydrides) polymers have been used in formulation of pulmonary nanovectors. As direct pulmonary administration of NPs is not feasible, by using the safe excipients, NPs could be converted to dry powder inhaler (DPI) formulations. These can provide a promising deposition and stability of NPs. In this article, the DPI formulations based on polymeric nanoparticles have been reviewed and categorized based on the polymer type used for preparation of NPs. PMID- 26818873 TI - Pharmacokinetic Considerations of Inhaled Pharmaceuticals for Systemic Delivery. AB - BACKGROUND: Systemic pulmonary delivery is considered to have advantages over oral or intravenous administration for certain drugs. METHODS: In this article, we review the effects of intrinsic drug properties and drug loading carriers on the pharmacokinetic parameters of inhaled drugs in the context of use in systemic pulmonary delivery. RESULTS: The delivery of drugs via inhalation can be advisable to achieve a fast onset of action; enhance the systemic bioavailability of drugs with poor oral absorption, including peptides and proteins; avoid invasive administration and improve patient compliance. To optimize the functioning of this delivery system, there is high demand for a systematic understanding of the pharmacokinetic characteristics, which are closely related to the pharmacodynamic and toxicological effects. CONCLUSION: The pharmacokinetic parameters of inhaled drug products are affected by many factors, including physiological and pathological variables and the intrinsic drug and formulation properties. PMID- 26818874 TI - Selected Engineering and Physicochemical Aspects of Systemic Drug Delivery by Inhalation. AB - Inhalation of aerosolized pharmaceuticals is a non-invasive and convenient method of drug delivery typically used for local treatment of lung diseases. Large absorption area of the pulmonary region opens up the possibility of fast and effective transfer of inhaled medicines to the circulation in order to obtain systemic effects. This review is devoted to selected albeit essential challenges of targeting aerosolized drugs to the blood via the pulmonary part of the respiratory system. The special attention is given to some physicochemical aspects of drug formulation which are essential for overcoming the air-blood barrier present in the lungs. It is deemed that a careful analysis of multifarious physical and engineering problems, related to aerosol fate in the lungs, is indispensable for a better design of inhalation delivery systems for systemic drugs. PMID- 26818875 TI - Aerosol Processing of Crumpled Graphene Oxide-based Nanocomposites for Drug Delivery. AB - BACKGROUND: The flexibility of graphene oxide (GO) nanosheets and their unique properties enable them to be excellent two dimensional (2D) building blocks for designing functional materials. Aerosol routes are proved to be a rational approach to fold the 2D flat GO nanosheets into 3D crumpled spheres to mitigate the restacking issue for large-scale applications, such as for drug delivery. RESULTS: The fundamentals of graphene, GO, and the crumpling process of GO nanosheets are summarized. Various crumpled graphene oxide (CGO)-based nanocomposites have been synthesized by aerosol routes. This mini review focuses on the state-of-the-art in the design and fabrication of these nanocomposites for a specific application in drug delivery. Various techniques are demonstrated and discussed to control the release rates, tailor the morphology, and adjust the components inside the nanocomposites. Potential risks and possible trends are also pointed out. CONCLUSION: Aerosol processing of CGO-based nanocomposites provides a promising approach to design functional nanomaterials for drug delivery and other related applications. PMID- 26818876 TI - Large Porous Hollow Particles: Lightweight Champions of Pulmonary Drug Delivery. AB - The deep lungs provide an efficient pathway for drugs to transport into the systemic circulation, as the extremely large surface area and thin epithelial membrane enable rapid drug transport to the blood stream. To penetrate into the deep lungs, aerosol particles with aerodynamic diameters of 1-3 um are optimal. Large porous hollow particles (LPHPs) can achieve this aerodynamic size range through enhanced porosity within the particles (typically < 0.4 g/cm(3)), which aerodynamically balances the large particle size (> 5 um, up to 30 um). The physical properties of these particles provide some key advantages compared to their small, nonporous counterparts through enhanced dispersibility, efficient deep lung deposition, and avoidance of phagocytic clearance. This review highlights the potential of LPHPs in pulmonary delivery of systemic drugs, with a focus on their critical attributes and key formulation aspects. In addition, three examples of LPHPs under development are presented to emphasize the potential of this technology to treat systemic diseases. PMID- 26818877 TI - The Role of Anionic Polysaccharides in the Preparation of Nanomedicines with Anticancer Applications. AB - Cancer has become one of the main causes of death in developed countries, and it is expected to be declared as the disease with the highest worldwide morbidity and mortality indexes in the coming decades. Nanomedicine aims to overcome some problems related to this prevalent disease, particularly the lack of efficient diagnostic and therapeutic tools. The most recent scientific advances, which have conducted to a more personalized medicine, were focused on the production of nanocarriers involved into the transport and the delivery of drugs to targeted cells. A wide variety of nanocarriers composed by different materials have been designed for their use as drug delivery systems. Polysaccharides have emerged as very useful biopolymers among all raw materials used in the preparation of these nanoplatforms. They are highly stable, non-toxic and biodegradable molecules, and also present some chemical properties which are very difficult to reproduce using artificial polymers. Anionic polymers, such as hyaluronic acid, heparin or alginate, present some structural and chemical characteristics which make them ideal polymers to prepare nanosystems with anticancer applications. This review will focus on the description of some anionic polysaccharides and the possibilities they offer towards the preparation of nanosystems with applications in cancer treatment and diagnostics. PMID- 26818878 TI - Neuroprotective Strategies in Glaucoma. AB - BACKGROUND: Glaucoma is characterized as a neuropathic disease that causes progressive degeneration of retinal ganglion cells (RGCs) in the retina, resulting in irreversible loss of vision. All conventional treatments for glaucoma are focused on reducing intraocular pressure (IOP) in the anterior chamber of the eye. However, these treatments alone are insufficient to halt the progression of the disease. As a result, neuroprotective strategies have been developed that prevent retinal neuron loss and disease progression. METHODS: The goal of this review is to summarize and discuss neuroprotective strategies in glaucoma at the level of the retina and the ganglion cell layer instead of treatments targeting IOP. Recent and past neuroprotective therapies used to prevent the loss of retinal ganglion cells, the loss of axons in the optic nerve and the loss of vision and function associated with glaucoma are presented. RESULTS: Pharmacological approaches have targeted specific receptors, signaling cascades and neurotrophic factors to induce neuroprotection in the retina, while others have focused on the mechanism of cellular loss associated with glaucoma, including excitotoxicity, oxidative stress and apoptotic processes. In addition to neuroprotective pharmacological treatments, stem cell, gene therapy and viral research have demonstrated neuroprotection against the loss of RGCs in glaucomatous conditions. CONCLUSION: It is likely that future development for glaucoma treatment will include a combination of these treatments to prevent the pathophysiology of glaucoma. PMID- 26818879 TI - Comprehensive auditory discrimination profiles recorded with a fast parametric musical multi-feature mismatch negativity paradigm. AB - OBJECTIVE: Mismatch negativity (MMN), a component of the auditory event-related potential (ERP) in response to auditory-expectancy violation, is sensitive to central auditory processing deficits associated with several clinical conditions and to auditory skills deriving from musical expertise. This sensitivity is more evident for stimuli integrated in complex sound contexts. This study tested whether increasing magnitudes of deviation (levels) entail increasing MMN amplitude (or decreasing latency), aiming to create a balanced version of the musical multi-feature paradigm towards measurement of extensive auditory discrimination profiles in auditory expertise or deficits. METHODS: Using electroencephalography, we measured MMNs in healthy young adults to six types of sound feature change (pitch, timbre, location, intensity, slide and rhythm) at three different magnitudes of deviation, embedded in a music-sounding context. We also behaviourally assessed the individual musical aptitude using the Musical Ear Test (MET). RESULTS: 16 of 18 sound feature changes elicited significant MMNs. For pitch, intensity, location, and slide, the MMN amplitude increased with increasing magnitude of feature change. We observed a ceiling effect for rhythm, and a floor effect for timbre. The slide MMN amplitude correlated positively with MET melody score and negatively with MET rhythm score. CONCLUSIONS: This novel paradigm provides an extensive, objective measure of auditory discrimination profile for different sound features embedded in a complex sound context. SIGNIFICANCE: The paradigm can be adopted to study the neurophysiology of individuals with music processing difficulties or with special musical skills, and may be a useful tool for investigating development, plasticity, and deficits of auditory processing. PMID- 26818880 TI - Ocular vestibular evoked myogenic potentials to vertex low frequency vibration as a diagnostic test for superior canal dehiscence. AB - OBJECTIVE: To explore ocular vestibular evoked myogenic potentials (oVEMP) to low frequency vertex vibration (125 Hz) as a diagnostic test for superior canal dehiscence (SCD) syndrome. METHODS: The oVEMP using 125 Hz single cycle bone conducted vertex vibration were tested in 15 patients with unilateral superior canal dehiscence (SCD) syndrome, 15 healthy controls and in 20 patients with unilateral vestibular loss due to vestibular neuritis. Amplitude, amplitude asymmetry ratio, latency and interaural latency difference were parameters of interest. RESULTS: The oVEMP amplitude was significantly larger in SCD patients when affected sides (53 MUVolts) were compared to non-affected (17.2 MUVolts) or compared to healthy controls (13.6 MUVolts). Amplitude larger than 33.8 MUVolts separates effectively the SCD ears from the healthy ones with sensitivity of 87% and specificity of 93%. The other three parameters showed an overlap between affected SCD ears and non-affected as well as between SCD ears and those in the two control groups. CONCLUSIONS: oVEMP amplitude distinguishes SCD ears from healthy ones using low-frequency vibration stimuli at vertex. SIGNIFICANCE: Amplitude analysis of oVEMP evoked by low-frequency vertex bone vibration stimulation is an additional indicator of SCD syndrome and might serve for diagnosing SCD patients with coexistent conductive middle ear problems. PMID- 26818881 TI - Enhanced motor learning with bilateral transcranial direct current stimulation: Impact of polarity or current flow direction? AB - OBJECTIVE: Bilateral transcranial direct current stimulation (TDCS) is superior to unilateral TDCS when targeting motor learning. This effect could be related to either the current flow direction or additive polarity-specific effects on each hemisphere. METHODS: This sham-controlled randomized study included fifty right handed healthy subjects in a parallel-group design who performed an exoskeleton based motor task of the proximal left arm on three consecutive days. Prior to training, we applied either sham, right anodal (a-TDCS), left cathodal (c-TDCS), concurrent a-TDCS and c-TDCS with two independent current sources and return electrodes (double source (ds)-TDCS) or classical bilateral stimulation (bi TDCS). RESULTS: Motor performance improved over time for both unilateral (a-TDCS, c-TDCS) and bilateral (bi-TDCS, ds-TDCS) TDCS montages. However, only the two bilateral paradigms led to an improvement of the final motor performance at the end of the training period as compared to the sham condition. There was no difference between the two bilateral stimulation conditions (bi-TDCS, ds-TDCS). CONCLUSION: Bilateral TDCS is more effective than unilateral stimulation due to its polarity-specific effects on each hemisphere rather than due to its current flow direction. SIGNIFICANCE: This study is the first systematic evaluation of stimulation polarity and current flow direction of bi-hemispheric motor cortex TDCS on motor learning of proximal upper limb muscles. PMID- 26818882 TI - Epileptiform discharge propagation: Analyzing spikes from the onset to the peak. AB - OBJECTIVE: To investigate how often discharge propagation occurs within the spikes recorded in patients evaluated for epilepsy surgery, and to assess its impact on the accuracy of source imaging. METHODS: Data were analyzed from 50 consecutive patients who had presurgical workup. Discharge propagation was analyzed using sequential voltage-maps of the averaged spikes, and principal components analysis. When propagation was detected, sources were modeled both at onset and peak. RESULTS: Propagation occurred in half of the patients. The median time of propagation between onset and peak was 17 ms. In 60% of the cases with propagation (15/25 patients) this remained in the same sub-lobar area where onset occurred. The accuracy of source imaging in cases of propagating spikes was 67% when only analyzing onset or peak. This was lower as compared to cases without propagation (79%). Combining source imaging at onset and at peak increased the accuracy to 83% for the propagating spikes. CONCLUSIONS: Propagation occurs often in patients with focal epilepsy, evaluated for surgery. In 40% of the propagating cases, the source of onset and peak were in different sub-lobar regions. SIGNIFICANCE: For optimal clinical utility, sources should be modeled both at onset and at peak epochs of the spikes. PMID- 26818883 TI - Erratum. Antipsychotic treatment and mortality in schizophrenia. PMID- 26818884 TI - Netherlands tops European healthcare index. PMID- 26818885 TI - Volatiles released by Chinese liquorice roots mediate host location behaviour by neonate Porphyrophora sophorae (Hemiptera: Margarodidae). AB - BACKGROUND: The cochineal scale, Porphyrophora sophorae (Hemiptera: Coccoidea, Margarodidae), is one of the most serious arthropod pests of Chinese liquorice, Glycyrrhiza uralensis (Fabaceae), an important medicinal herb. The adult females tend to deposit the ovisacs in soil relatively far away from liquorice plants. After hatching, neonates move out of the soil and may use chemical cues to search for new hosts. RESULTS: We collected and analysed the volatiles from soils with and without liquorice roots, and chromatographic profiles revealed hexanal, beta pinene and hexanol as potential host-finding cues for P. sphorae. The attractiveness of these compounds to neonates was studied in the laboratory using four-arm olfactometer bioassays. The larvae showed a clear preference for beta pinene over hexanal and hexanol, as well as all possible combinations of the three compounds. In addition, a field experiment confirmed that beta-pinene was significantly more attractive than hexanal and hexanol. CONCLUSION: Newly eclosed larvae of P. sphorae exploit root volatiles as chemical cues to locate their host plant. beta-Pinene proved to be the major chemical cue used by P. sphorae neonates searching for roots of their host plant. (c) 2016 Society of Chemical Industry. PMID- 26818886 TI - Global transcriptomic responses of Escherichia coli K-12 to volatile organic compounds. AB - Volatile organic compounds (VOCs) are commonly used as solvents in various industrial settings. Many of them present a challenge to receiving environments, due to their toxicity and low bioavailability for degradation. Microorganisms are capable of sensing and responding to their surroundings and this makes them ideal detectors for toxic compounds. This study investigates the global transcriptomic responses of Escherichia coli K-12 to selected VOCs at sub-toxic levels. Cells grown in the presence of VOCs were harvested during exponential growth, followed by whole transcriptome shotgun sequencing (RNAseq). The analysis of the data revealed both shared and unique genetic responses compared to cells without exposure to VOCs. Results suggest that various functional gene categories, for example, those relating to Fe/S cluster biogenesis, oxidative stress responses and transport proteins, are responsive to selected VOCs in E. coli. The differential expression (DE) of genes was validated using GFP-promoter fusion assays. A variety of genes were differentially expressed even at non-inhibitory concentrations and when the cells are at their balanced-growth. Some of these genes belong to generic stress response and others could be specific to VOCs. Such candidate genes and their regulatory elements could be used as the basis for designing biosensors for selected VOCs. PMID- 26818888 TI - An unusual cause of back pain. PMID- 26818887 TI - Lysosomal cholesterol accumulation in macrophages leading to coronary atherosclerosis in CD38(-/-) mice. AB - The disruption in transportation of oxLDL-derived cholesterol and the subsequent lipid accumulation in macrophages are the hallmark events in atherogenesis. Our recent studies demonstrated that lysosomal Ca(2+) messenger of nicotinic acid adenine dinucleotide phosphate (NAADP), an enzymatic product of CD38 ADP ribosylcyclase (CD38), promoted lipid endocytic trafficking in human fibroblast cells. The current studies are designed to examine the functional role of CD38/NAADP pathway in the regulation of lysosomal cholesterol efflux in atherosclerosis. Oil red O staining showed that oxLDL concentration-dependently increased lipid buildup in bone marrow-derived macrophages from both wild type and CD38(-/-) , but to a significant higher extent with CD38 gene deletion. Bodipy 493/503 fluorescence staining found that the deposited lipid in macrophages was mainly enclosed in lysosomal organelles and largely enhanced with the blockade of CD38/NAADP pathway. Filipin staining and direct measurement of lysosome fraction further revealed that the free cholesterol constituted a major portion of the total cholesterol segregated in lysosomes. Moreover, in situ assay disclosed that both lysosomal lumen acidity and the acid lipase activity were reduced upon cholesterol buildup in lysosomes. In CD38(-/-) mice, treatment with Western diet (12 weeks) produced atherosclerotic damage in coronary artery with striking lysosomal cholesterol sequestration in macrophages. These data provide the first experimental evidence that the proper function of CD38/NAADP pathway plays an essential role in promoting free cholesterol efflux from lysosomes and that a defection of this signalling leads to lysosomal cholesterol accumulation in macrophages and results in coronary atherosclerosis in CD38(-/-) mice. PMID- 26818889 TI - Length Distribution of Ancestral Tracks under a General Admixture Model and Its Applications in Population History Inference. AB - The length of ancestral tracks decays with the passing of generations which can be used to infer population admixture histories. Previous studies have shown the power in recovering the histories of admixed populations via the length distributions of ancestral tracks even under simple models. We believe that the deduction of length distributions under a general model will greatly elevate the power. Here we first deduced the length distributions under a general model and proposed general principles in parameter estimation and model selection with the deduced length distributions. Next, we focused on studying the length distributions and its applications under three typical special cases. Extensive simulations showed that the length distributions of ancestral tracks were well predicted by our theoretical framework. We further developed a new method, AdmixInfer, based on the length distributions and good performance was observed when it was applied to infer population histories under the three typical models. Notably, our method was insensitive to demographic history, sample size and threshold to discard short tracks. Finally, good performance was also observed when applied to some real datasets of African Americans, Mexicans and South Asian populations from the HapMap project and the Human Genome Diversity Project. PMID- 26818890 TI - Discontinuing benzodiazepines: best practices. AB - In July 2015, the Canadian Agency for Drugs and Technologies in Health (CADTH) released a Rapid Response report summary, with a critical appraisal, on discontinuation strategies for patients with long-term benzodiazepines (BDZ) use. The CADTH document is a review of the literature. It includes studies whose intervention is BDZ discontinuation. Also, clinical guidelines, systematic reviews and meta-analyses are included. What emerges from the CADTH guidelines is that the best strategy remains gradual tapering of BDZ with little evidence for the use of adjunctive medications. The results show that simple interventions such as discontinuation letters from clinicians, self-help information and support in general, added to gradual tapering may be associated with a two- to three-fold higher chance of successful withdrawal, compared with treatment as usual. We suggest possible implications for day-to-day clinical practice. PMID- 26818891 TI - Results of patch testing in Indonesian shoe factory workers. PMID- 26818892 TI - Gestational diabetes: Glycaemic predictors for fetal macrosomia and maternal risk of future diabetes. AB - AIMS: To investigate how glucose levels at diagnosis of gestational diabetes (GDM) are associated with infant birth weight and long-term risk of manifest diabetes mellitus in the mother. METHODS: In a case control study GDM pregnancies (n=2085) were compared with non-GDM pregnancies matched for day of delivery and obstetric unit (n=3792). GDM was defined as capillary blood glucose (cB-glucose) >=9.0mmol/l (plasma glucose >=10.0mmol/l) after a 75g oral glucose tolerance test (OGTT). The GDM cohort were followed up 8.5-13.5yrs after initial diagnosis with a questionnaire, answered by 1324 GDM women (65%). RESULTS: GDM women had higher mean infant birth-weight compared with controls (3682g vs. 3541g, P<0.001). In multiple linear regression analysis, birth weight was positively correlated to fasting cB-glucose at GDM diagnosis (P<0.001), increased week of gestation (P<0.001) and BMI before pregnancy (P<0.003), while 2h OGTT cB-glucose values >=9.0mmol/l were not related. Infants born to mothers with fasting cB-glucose <=4.5mmol/l had no increased mean birth-weight or macrosomia (>=4500g) compared to controls. In the follow up 334/1324 women (25%) of the GDM women had developed diabetes, 215 type 2 diabetes, 46 type 1 diabetes and 72 unclassified diabetes. In logistic regression fasting cB-glucose and 2h OGTT cB-glucose at diagnosis of GDM as well as BMI >25 and origin outside Europe were risk factors for manifest diabetes. CONCLUSIONS: Fasting blood glucose at diagnosis of GDM gives important information besides 2h OGTT glucose about pregnancy outcome and future risk for maternal diabetes. PMID- 26818893 TI - Willingness to initiate insulin among adults with type 2 diabetes in Australian primary care: Results from the Stepping Up Study. AB - AIMS: To determine 'hypothetical willingness' to initiate insulin, and identify associated factors, among adults with type 2 diabetes (T2DM) in primary care for whom insulin is clinically indicated. METHODS: Eligible participants were adults with T2DM with an HbA1c >=7.5% (58mmol/mol) and prescribed maximum oral hypoglycaemic agents. A total of 261 participants were recruited from 74 Victorian general practices: mean age 62+/-10 years; 39% (n=103) women; diabetes duration 10+/-6 years; HbA1c 9.0+/-1.3% (75+/-14mmol/mol). Data collected by the Stepping Up Study: demographic and clinical characteristics, 'willingness' to initiate insulin, insulin appraisals, depressive symptoms, and diabetes-related distress. A multinomial regression investigated predictors of 'willingness'. RESULTS: Nineteen percent (n=50) were 'very willing' to initiate insulin, if recommended. The final regression model (R(2)=.44, chi(2)(12) 145.91, p<.001) demonstrated higher socioeconomic status and less negative attitudes to insulin were associated with increased willingness to initiate insulin. CONCLUSIONS: Among adults with T2DM for whom insulin is clinically indicated, only one in five are 'very willing' to begin insulin therapy. Independent of demographics, clinical factors and emotional wellbeing, insulin appraisals were associated with 'willingness'. This study highlights the importance of addressing attitudinal barriers to insulin therapy among adults with T2DM in primary care to improve insulin receptiveness. PMID- 26818894 TI - Calcium channel blocker use is associated with lower fasting serum glucose among adults with diabetes from the REGARDS study. AB - BACKGROUND: Ca(2+) channel blockers (CCB) and verapamil in particular prevented beta-cell apoptosis and enhanced endogenous insulin levels in recent studies of mouse models of diabetes. Verapamil's effect on serum glucose levels in humans with diabetes is not described. METHODS: We used data from the REasons for Geographic and Racial Differences in Stroke (REGARDS), a national cohort study of community-dwelling middle-aged and older adults, enrolled between 2003 and 2007 from the continental United States. We examined associations of CCB and verapamil use with fasting serum glucose among 4978 adults with diabetes, controlling for covariates in generalized linear models (GLM). FINDINGS: The sample included 1484 (29.6%) CCB users, of which 174 (3.4%) were verapamil users. In fully adjusted GLMs, CCB users had 5mg/dL lower serum glucose compared to non-users. Verapamil users had on average 10mg/dL lower serum glucose compared to CCB non-users with substantially greater differences among insulin users: 24mg/dL lower serum glucose among users of insulin in combination with oral agents and 37mg/dL lower among users of insulin alone. INTERPRETATION: CCB and in particular verapamil use was associated with lower fasting blood glucose levels among REGARDS participants with diabetes. FUNDING: UO1NS041588 from the National Institute of Neurological Disorders and Stroke, NIH; K24HL111154 and R01HL080477 from the National Heart, Lung, and Blood Institute. PMID- 26818895 TI - Ice-pack Dermatosis: A Diagnositic Pitfall for Dermatopathologists that Mimics Lupus Erythematosus. PMID- 26818899 TI - Magnetic Ordering in Sr3YCo4O10+x. AB - Transition-metal oxides often exhibit complex magnetic behavior due to the strong interplay between atomic-structure, electronic and magnetic degrees of freedom. Cobaltates, especially, exhibit complex behavior because of cobalt's ability to adopt various valence and spin state configurations. The case of the oxygen deficient perovskite Sr3YCo4O10+x (SYCO) has attracted considerable attention because of persisting uncertainties about its structure and the origin of the observed room temperature ferromagnetism. Here we report a combined investigation of SYCO using aberration-corrected scanning transmission electron microscopy and density functional theory calculations. Guided by theoretical results on Co-O distances projected on different planes, the atomic-scale images of several different orientations, especially of the fully oxygenated planes, allow the unambiguous extraction of the underlying structure. The calculated magnetic properties of the new structure are in excellent agreement with the experimental data. PMID- 26818900 TI - [Education of people with type 2 diabetes through peers with diabetes: is it cost effective?]. AB - INTRODUCTION: Inadequate quality of care provided to people with type 2 diabetes mellitus, generates a significant socioeconomic burden and a serious public health problem. Diabetes education through peers with diabetes is an alternative to that provided by professional educators (traditional education) which achieves non-inferior results. However, there is little evidence of cost-effectiveness of education trough peers over traditional education. OBJECTIVE: To evaluate cost effectiveness of education of people with type 2 diabetes mellitus, during a year, by a team of professional educators (traditional education) versus education and support delivered by trained peers with diabetes. METHODS: Cost effectiveness analysis based on a randomized prospective clinical study conducted in the city of La Plata, including 199 people with type 2 diabetes mellitus, divided in two groups:, one receiving traditional education and another receiving the same education but delivered by peer educators with type 2 diabetes mellitus. Change in glycosylated hemoglobin (HbA1c) was considered as a primary indicator of effectiveness and secondary indicators were others, such as body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol and triglyceride levels. The direct cost of each strategy was estimated based on resources used in the trial, evaluating three cost scenarios for peer education. The strength of the results was assessed by univariate sensitivity analysis. RESULTS: Cost per unit decrease (%) in HbA1c: traditional education: $2 621; peer education: $1 508, $1 779 y $2 071 for each of the three scenarios considered (scenario 1, scenario 2, scenario 3), respectively. For each $100 invested a decrease of 0.04% in the HbA1c with traditional education was achieved; and 0.07% in scenario 1; 0.06% in scenario 2 and 0.05% in scenario 3, with education delivered by peer educators. Sensitivity analysis showed the strength of the results. CONCLUSION: Education of type 2 diabetes mellitus patients through peers as a complement to control and treatment of the disease, is cost-effective compared to traditional education. PMID- 26818901 TI - The class I phosphoinositide 3-kinases alpha and beta control antiphospholipid antibodies-induced platelet activation. AB - Antiphospholipid syndrome (APS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies (aPL) associated with increased thrombotic risk and pregnancy morbidity. Although aPL are heterogeneous auto antibodies, the major pathogenic target is the plasma protein beta2-glycoprotein 1. The molecular mechanisms of platelet activation by aPL remain poorly understood. Here, we explored the role of the class IA phosphoinositide 3-kinase (PI3K) alpha and beta isoforms in platelet activation by aPL. Compared to control IgG from healthy individuals, the IgG fraction isolated from patients with APS potentiates platelet aggregation induced by low dose of thrombin in vitro and increases platelet adhesion and thrombus growth on a collagen matrix under arterial shear rate through a mechanism involving glycoprotein Ib (GPIb) and Toll Like Receptor 2 (TLR-2). Using isoforms-selective pharmacological PI3K inhibitors and mice with megakaryocyte/platelet lineage-specific inactivation of class IA PI3K isoforms, we demonstrate a critical role of the PI3Kbeta and PI3Kalpha isoforms in platelet activation induced by aPL. Our data show that aPL potentiate platelet activation through GPIbalpha and TLR-2 via a mechanism involving the class IA PI3Kalpha and beta isoforms, which represent new potential therapeutic targets in the prevention or treatment of thrombotic events in patients with APS. PMID- 26818898 TI - Gingival fibromatosis: clinical, molecular and therapeutic issues. AB - Gingival fibromatosis is a rare and heterogeneous group of disorders that develop as slowly progressive, local or diffuse enlargements within marginal and attached gingiva or interdental papilla. In severe cases, the excess tissue may cover the crowns of the teeth, thus causing functional, esthetic, and periodontal problems, such as bone loss and bleeding, due to the presence of pseudopockets and plaque accumulation. It affects both genders equally. Hereditary, drug-induced, and idiopathic gingival overgrowth have been reported. Hereditary gingival fibromatosis can occur as an isolated condition or as part of a genetic syndrome. The pathologic manifestation of gingival fibromatosis comprises excessive accumulation of extracellular matrix proteins, of which collagen type I is the most prominent example. Mutation in the Son-of-Sevenless-1 gene has been suggested as one possible etiological cause of isolated (non-syndromic) hereditary gingival fibromatosis, but mutations in other genes are also likely to be involved, given the heterogeneity of this condition. The most attractive concept of mechanism for drug-induced gingival overgrowth is epithelial-to mesenchymal transition, a process in which interactions between gingival cells and the extracellular matrix are weakened as epithelial cells transdifferentiate into fibrogenic fibroblast-like cells. The diagnosis is mainly made on the basis of the patient's history and clinical features, and on histopathological evaluation of affected gingiva. Early diagnosis is important, mostly to exclude oral malignancy. Differential diagnosis comprises all pathologies in the mouth with excessive gingival overgrowth. Hereditary gingival fibromatosis may present as an autosomal-dominant or less commonly autosomal-recessive mode of inheritance. If a systemic disease or syndrome is suspected, the patient is directed to a geneticist for additional clinical examination and specialized diagnostic tests. Treatments vary according to the type of overgrowth and the extent of disease progression, thus, scaling of teeth is sufficient in mild cases, while in severe cases surgical intervention is required. Prognosis is precarious and the risk of recurrence exists. PMID- 26818902 TI - Meta-analysis of sex differences in gene expression in schizophrenia. AB - Schizophrenia is a severe psychiatric disorder which influences around 1% of the worldwide population. Differences between male and female patients with schizophrenia have been noted. There is an earlier age of onset in males compared with females with this diagnosis, and in addition, there are differences in symptom profiles between the sexes. The underlying molecular mechanism of sex difference remains unclear. Here we present a comprehensive analysis to reveal the sex differences in gene expression in schizophrenia with stringent statistics criteria. We compiled a data set consisting of 89 male controls, 90 male schizophrenia patients, 35 female controls and 32 female schizophrenia patients from six independent studies of the prefrontal cortex (PFC) in postmortem brain. When we tested for a sex by diagnosis interaction on gene expression, 23 genes were up-regulated and 23 genes were down-regulated in the male group (q-value < 0.05), several genes are related to energy metabolism, while 4 genes are located on sex chromosome. No genes were statistically significant in the female group when multiple testing correction were conducted (q-value <0.05), most likely due to the small sample size. Our protocol and results from the male group provide a starting point for identifying the underlying different mechanism between male and female schizophrenia patients. PMID- 26818904 TI - Use of natural mordenite to remove chromium (III) and to neutralize pH of alkaline waste waters. AB - The natural mordenite from Palmarito de Cauto deposit (PZ), Cuba, was studied in this work as an ion exchanger to remove Cr(3+) cations from alkaline aqueous solutions at different pH and chromium concentrations. The mordenite stability under cyclic treatment processes with alkaline solutions and its capacity to decrease the pH of the solutions was also analyzed. It was shown that PZ removes Cr(3+) ions from alkaline solutions, and it happens independently of the starting chromium concentration and the pH of the exchange solution used. This material has an important neutralizing effect on alkaline solutions, expressed in a significant pH decrease from the early stages of the treatments. For solutions with initial pH equal to 11, it decreases to a value of around seven. The stability of this material is not affected significantly after continuous cyclic treatment with NaOH solution, which shows that mordenite, in particular from Palmarito de Cauto deposit, has high stability in alkaline solutions. The results are important as they suggest that natural zeolites may be of interest in treatments of alkaline industrial waste effluents. PMID- 26818905 TI - A Systematic Review of Adolescent Self-Management and Weight Loss. AB - INTRODUCTION: The aim of this review is to evaluate self-management interventions among overweight and obese adolescents to direct future research and practice. METHODS: Studies published between 2008 and 2014 were identified by electronic database searches. The Jadad Scoring of Quality Reports of Randomized Clinical Trials was used to evaluate the quality of the studies with subsequent reviews. RESULTS: Out of 69 studies, 10 randomized controlled trials were reviewed after all inclusion and exclusion criteria were met. Quality scores ranged from 7 to 11 out of 13 (M = 9.2, SD = 1.13). For the majority of studies, self-management strategies for weight loss were found to be significant for a mix of behavioral, psychological, anthropometric, and metabolic outcomes. DISCUSSION: Findings indicated that interventions were most successful when incorporating family members. Self-management interventions that include a combination of appropriate diet, physical activity, and behavioral strategies with a family component are recommended. PMID- 26818906 TI - Genetic and functional analysis of a Li Fraumeni syndrome family in China. AB - Li Fraumeni syndrome (LFS) is a rare familial cancer predisposition syndrome with autosomal-dominant inheritance, occurring as frequently as one in 5,000-20,000 individuals. However, no LFS case has been reported from mainland China although it constitutes one quarter of population on earth. In this study, we identified, to our best knowledge, the first Li Fraumeni syndrome family in China. Six family members were affected with various tumors. A TP53 mutation (c.730G > A; p.G244S) co-segregated with the tumor phenotype within this family. Functional analysis indicated that G244S mutation disrupted the transactivity, DNA-binding and cell growth inhibition activity of p53 protein. Two available tumor samples (medulloblastoma and choroid plexus papilloma) underwent large rearrangement in the chromosomes and loss of wild-type TP53. Our data warranted further studies on the prevalence of germline TP53 mutation in various tumor patients in China. PMID- 26818907 TI - Relating calls to US poison centers for potential exposures to medications to Centers for Disease Control and Prevention reporting of influenza-like illness. AB - CONTEXT: The Centers for Disease Control (CDC) monitors influenza like illness (ILI) and the National Poison Data System (NPDS) warehouses call data uploaded by US poison centers regarding reported exposures to medication. OBJECTIVE: We examined the relationship between calls to poison centers regarding reported exposures to medications commonly used to treat ILI and weekly reports of ILI. MATERIALS AND METHODS: The CDC reports ILI, by age group, for each of 10 Health and Human Services (HHS) regions. We examined NPDS summary data from calls reported to poison centers regarding reported exposures to acetaminophen, cough/cold medications, and promethazine, for the same weeks, age groups, and HHS regions for influenza seasons 2000-2013. ILI and NPDS exposures were examined using graphical plots, descriptive statistics, stepwise regression analysis, and Geographic Information Systems (GIS). RESULTS: About 5,101,841 influenza-like illness cases were reported to the CDC, and 2,122,940 calls regarding reported exposures to medications commonly used to treat ILI, were reported by poison centers to the NPDS over the 13 flu seasons. Analysis of stepwise models of the linear untransformed data involving 24 NPDS data groups and for 60 ILI measures, over the 13 influenza seasons, demonstrated that reported exposures to medications used to treat ILI correlated with reported cases of ILI with a median R(2 )=( )0.489 (min R(2 )=( )0.248, max R(2 )=( )0.717), with mean +/- SD of R(2 )=( )0.494 +/- 0.121. Median number of parameters used (degrees of freedom - 1) was 7. CONCLUSIONS: NPDS data regarding poison center calls for selected ILI medication exposures were highly correlated with CDC ILI data. Since NPDS data are available in real time, it provides complimentary ILI monitoring. This approach may provide public health value in predicting other illnesses which are not currently as thoroughly monitored. PMID- 26818908 TI - Strongly enhanced ultraviolet emission of an Au@SiO2/ZnO plasmonic hybrid nanostructure. AB - We present the surface plasmon polariton (SPP)-enhanced ultraviolet (UV) emission of an Au@SiO2/ZnO hybrid nanostructure. We achieved approximately 20- and 8-fold enhancements of the UV-emitting intensities from Au-SPP coupled nanometre- and micrometre-scaled ZnO wires through an optimized 5 nm-thick SiO2 spacer compared to that obtained from bare ZnO on a Si substrate without SPP coupling. Cathodoluminescence measurements and simulations demonstrated that the plasmonic hybrid nanostructure enables the strong localization of the SPP field, resulting in significantly enhanced UV emission. This plasmonic structure paves the way to nanoscale UV-optical lasers and sensors. PMID- 26818910 TI - Mistimed wheel running interferes with re-entrainment of circadian Per1 rhythms in the mouse skeletal muscle and lung. AB - Previously, we showed the acceleration of re-entrainment to 8-h phase-advanced light/dark cycles (LD) in the circadian Per1 expression rhythms of the mouse lung and skeletal muscle by 3-h wheel running (WR) at the beginning of shifted dark phase. In the present study, the effects of WR at the end of shifted dark phase were examined on the re-entrainment in mice. LD was advanced by shortening and was delayed by lengthening the first light period in the phase-advance and phase delay protocol, respectively. Shifted LD was continued for 4 days, which was followed by constant darkness (DD). Per1 expression was measured in the cultured tissues obtained on the first day of DD from mice carrying a bioluminescence reporter of Per1 expression. In the phase-advance protocol, re-entrainment was not influenced by WR in any circadian rhythm examined. In the phase-delay protocol, re-entrainment of the circadian locomotor rhythm was not affected by WR. However, re-entrainment of circadian Per1 rhythm was significantly decelerated in the skeletal muscle and lung. These findings indicate that the effects of WR on re-entrainment depend on the time of day and the peripheral tissues. Mistimed WR interferes with re-entrainment of circadian rhythms in the lung and skeletal muscle. PMID- 26818909 TI - Reference genes for accessing differential expression among developmental stages and analysis of differential expression of OBP genes in Anastrepha obliqua. AB - The West Indian fruit fly, Anastrepha obliqua, is an important agricultural pest in the New World. The use of pesticide-free methods to control invasive species such as this reinforces the search for genes potentially useful in their genetic control. Therefore, the study of chemosensory proteins involved with a range of responses to the chemical environment will help not only on the understanding of the species biology but may also help the development of environmentally friendly pest control strategies. Here we analyzed the expression patterns of three OBP genes, Obp19d_2, Obp56a and Obp99c, across different phases of A. obliqua development by qPCR. In order to do so, we tested eight and identified three reference genes for data normalization, rpl17, rpl18 and ef1a, which displayed stability for the conditions here tested. All OBPs showed differential expression on adults and some differential expression among adult stages. Obp99c had an almost exclusive expression in males and Obp56a showed high expression in virgin females. Thereby, our results provide relevant data not only for other gene expression studies in this species, as well as for the search of candidate genes that may help in the development of new pest control strategies. PMID- 26818912 TI - Leaf Length Tracker: a novel approach to analyse leaf elongation close to the thermal limit of growth in the field. AB - Leaf growth in monocot crops such as wheat and barley largely follows the daily temperature course, particularly under cold but humid springtime field conditions. Knowledge of the temperature response of leaf extension, particularly variations close to the thermal limit of growth, helps define physiological growth constraints and breeding-related genotypic differences among cultivars. Here, we present a novel method, called 'Leaf Length Tracker' (LLT), suitable for measuring leaf elongation rates (LERs) of cereals and other grasses with high precision and high temporal resolution under field conditions. The method is based on image sequence analysis, using a marker tracking approach to calculate LERs. We applied the LLT to several varieties of winter wheat (Triticum aestivum), summer barley (Hordeum vulgare), and ryegrass (Lolium perenne), grown in the field and in growth cabinets under controlled conditions. LLT is easy to use and we demonstrate its reliability and precision under changing weather conditions that include temperature, wind, and rain. We found that leaf growth stopped at a base temperature of 0 degrees C for all studied species and we detected significant genotype-specific differences in LER with rising temperature. The data obtained were statistically robust and were reproducible in the tested environments. Using LLT, we were able to detect subtle differences (sub-millimeter) in leaf growth patterns. This method will allow the collection of leaf growth data in a wide range of future field experiments on different graminoid species or varieties under varying environmental or treatment conditions. PMID- 26818911 TI - Identification of a G-Protein Subunit-alpha11 Gain-of-Function Mutation, Val340Met, in a Family With Autosomal Dominant Hypocalcemia Type 2 (ADH2). AB - Autosomal dominant hypocalcemia (ADH) is characterized by hypocalcemia, inappropriately low serum parathyroid hormone concentrations and hypercalciuria. ADH is genetically heterogeneous with ADH type 1 (ADH1), the predominant form, being caused by germline gain-of-function mutations of the G-protein coupled calcium-sensing receptor (CaSR), and ADH2 caused by germline gain-of-function mutations of G-protein subunit alpha-11 (Galpha11 ). To date Galpha11 mutations causing ADH2 have been reported in only five probands. We investigated a multigenerational nonconsanguineous family, from Iran, with ADH and keratoconus which are not known to be associated, for causative mutations by whole-exome sequencing in two individuals with hypoparathyroidism, of whom one also had keratoconus, followed by cosegregation analysis of variants. This identified a novel heterozygous germline Val340Met Galpha11 mutation in both individuals, and this was also present in the other two relatives with hypocalcemia that were tested. Three-dimensional modeling revealed the Val340Met mutation to likely alter the conformation of the C-terminal alpha5 helix, which may affect G-protein coupled receptor binding and G-protein activation. In vitro functional expression of wild-type (Val340) and mutant (Met340) Galpha11 proteins in HEK293 cells stably expressing the CaSR, demonstrated that the intracellular calcium responses following stimulation with extracellular calcium, of the mutant Met340 Galpha11 led to a leftward shift of the concentration-response curve with a significantly (p < 0.0001) reduced mean half-maximal concentration (EC50 ) value of 2.44 mM (95% CI, 2.31 to 2.77 mM) when compared to the wild-type EC50 of 3.14 mM (95% CI, 3.03 to 3.26 mM), consistent with a gain-of-function mutation. A novel His403Gln variant in transforming growth factor, beta-induced (TGFBI), that may be causing keratoconus was also identified, indicating likely digenic inheritance of keratoconus and ADH2 in this family. In conclusion, our identification of a novel germline gain-of-function Galpha11 mutation, Val340Met, causing ADH2 demonstrates the importance of the Galpha11 C-terminal region for G-protein function and CaSR signal transduction. (c) 2016 American Society for Bone and Mineral Research. PMID- 26818913 TI - Translating knowledge for action against stroke--using 5-minute videos for stroke survivors and caregivers to improve post-stroke outcomes: study protocol for a randomized controlled trial (Movies4Stroke). AB - BACKGROUND: Two thirds of the global mortality of stroke is borne by low and middle income countries (LMICs). Pakistan is the world's sixth most populous country with a stroke-vulnerable population and is without a single dedicated chronic care center. In order to provide evidence for a viable solution responsive to this health care gap, and leveraging the existing >70% mobile phone density, we thought it rational to test the effectiveness of a mobile phone-based video intervention of short 5-minute movies to educate and support stroke survivors and their primary caregivers. METHODS: Movies4Stroke will be a randomized control, outcome assessor blinded, parallel group, single center superiority trial. Participants with an acute stroke, medically stable, with mild to moderate disability and having a stable primary caregiver will be included. After obtaining informed consent the stroke survivor-caregiver dyad will be randomized. Intervention participants will have the movie program software installed in their phone, desktop, or Android device which will allow them to receive, view and repeat 5-minute videos on stroke-related topics at admission, discharge and first and third months after enrollment. The control arm will receive standard of care at an internationally accredited center with defined protocols. The primary outcome measure is medication adherence as ascertained by a locally validated Morisky Medication Adherence Scale and control of major risk factors such as blood pressure, blood sugar and blood cholesterol at 12 months post discharge. Secondary outcome measures are post-stroke complications and mortality, caregiver knowledge and change in functional outcomes after acute stroke at 1, 3, 6, 9 and 12 months. Movies4Stroke is designed to enroll 300 participant dyads after inflating 10% to incorporate attrition and non-compliance and has been powered at 95% to detect a 15% difference between intervention and usual care arm. Analysis will be done by the intention-to-treat principle. DISCUSSION: Movies4Stroke is a randomized trial testing an application aimed at supporting caregivers and stroke survivors in a LMIC with no rehabilitation or chronic support systems. TRIAL REGISTRATION: NCT02202330 (28 January 2015). PMID- 26818914 TI - The evaluation of miRNAs on thyroid FNAC: the promising role of miR-375 in follicular neoplasms. AB - Fine needle aspiration cytology (FNAC) plays an essential role in the evaluation of thyroid nodules especially for the category of follicular neoplasms (FN) representing 25 % of all thyroid cases including different neoplastic entities. Hence, one of the most promising areas is the application of molecular tests to FNAC. Among them, microRNAs (miRNA),identified as negative (post-transcriptional) gene expression regulators involved in tumor development, are likely to discriminate among FNs. Limited data explored the use of miRNAs on FNAC as well as their role in the malignant risk stratification. We aimed to define whether liquid-based cytology (LBC) is a valid method for miRNA evaluation. From June 2014 to March 2015, we enrolled 27FNs with histological follow-up. In the same reference period, 13 benign nodules (BN) and 20 positive for malignancy (PM) were selected as controls. Histologically, FNs resulted in 14 malignancies (3 papillary thyroid carcinoma-PTC and 11 follicular variant of PTC-FVPC) and 13 follicular adenomas (FA). The 20 PMs included two FVPC, 16 PTC and two medullary thyroid carcinoma (MTC). Five miRNAs (10b, 92a, 221/222 cluster, and 375) were studied on LBC and quantified by real-time PCR. Only miR-375 was over-expressed in the FNs diagnosed as carcinomas and in the PMs. A cut-off of 12 miR-375/U6 relative ratio recognized all BNs and 95 % PMs. Specifically, in each category, FVPCs and PTCs did not show any difference while MTCs had the highest value. miR 375 shows 97.1 % sensitivity, 100 % specificity, 96.3 % negative predictive value (NPV), 100 % positive predictive value (PPV), and 98.3 % diagnostic accuracy. LBC is suitable for miRNAs evaluation. miR-375 resulted over-expressed in all malignant FNs and 95 % PMs. It may represent a valid aid in ruling out BNs and supporting PTCs and/or FVPCs. PMID- 26818915 TI - mTORC1 pathway mediates beta cell compensatory proliferation in 60 % partial pancreatectomy mice. AB - Beta cell replication is the major component for maintenance of beta cell mass in adult rodents; however, little is known about what is the earliest signals that initiate rodent beta cell proliferation. The mTORC1 pathway integrates signals from growth factors and nutrients and regulates cell growth and survival. Here, we used normoglycemic 60 % partial-pancreatectomy (60 % Px) mouse model to determine whether mTORC1 pathway was required for compensatory beta cell proliferation. C57BL/6 J male mice were subjected to 60 % Px or sham operation, and subsequently treated with either rapamycin or vehicle for 7 days. Metabolic profile, pancreatic beta cell mass, and proliferation were examined, and expression levels of cell cycle regulators were determined. Beta cell proliferation was increased by 2.5-fold, and mTORC1 signaling was activated in islets post-Px. Rapamycin treatment impaired glucose tolerance and glucose stimulating insulin secretion in 60 % Px mice, but did not affect their insulin sensitivity in peripheral tissue. Rapamycin inhibited mTORC1 activity in beta cells, suppressed compensatory beta cell proliferation and growth, and reduced beta cell mass and insulin content in 60 % Px mice. Px caused an increase of the cyclin D2 at protein level and promoted cyclin D2 nuclear localization in an mTOR dependent manner. Disrupting mTORC1 signaling suppressed cell proliferation and simultaneously diminished cyclin D2 protein abundance in RINm5F cells. Our data demonstrated that mTORC1 plays an essential role in beta cell adaption to significant beta cell mass loss in 60 % Px model and in early compensatory beta cell proliferation via cyclin D2 pathway. PMID- 26818916 TI - Interaction between MLL3 genetic polymorphisms, smoking, and alcohol drinking in laryngeal cancer: a case-control study. AB - A previous study indicated that MLL3 genetic polymorphisms were associated with human cancer. However, whether MLL3 genetic variants are associated with the risk of laryngeal cancer is not clear. This study investigated the association between MLL3 gene polymorphisms and laryngeal cancer in a Chinese population. Four polymorphisms of the MLL3 gene (rs6943984, rs4725443, rs3800836, rs6464211) were genotyped using the TaqMan method in 592 patients with larynx cancer and 602 age- and sex-matched noncancer controls. We found that rs6943984 and rs4725443 of the MLL3 gene were significantly associated with the risk of larynx cancer after Bonferroni correction. The minor allele A for rs6943984 was associated with increased larynx cancer risk (P < 0.001, OR = 1.960, 95% CI = 1.587-2.420). C allele frequency (0.151) for rs4725443 was significantly higher in the case group than the control group (0.072, P < 0.001). Haplotype analyses showed that haplotypes A-T-A-C and G-T-G-C increased the risk of laryngeal cancer (OR = 2.406, 95% CI: 1.820-3.180, P < 0.001; OR = 1.399, 95% CI: 1.180-1.659, respectively), and haplotypes G-T-A-C and G-T-G-T significantly reduced the risk of laryngeal cancer (OR = 0.332, 95% CI: 0.271-0.408, P < 0.001; OR = 0.742, 95% CI: 0.607-0.908, respectively). We also found that MLL3 rs6943984 and rs4725443 polymorphisms had synergistic effects with smoking or alcohol drinking for the risk of laryngeal cancer. This study indicated that MLL3 genetic polymorphisms and haplotypes were associated with larynx cancer in a Chinese population. There was a mutually synergistic effect between smoking, alcohol drinking, and MLL3 gene polymorphisms for laryngeal cancer. PMID- 26818917 TI - Maternal perception of the occurrence of traumatic dental injuries in children: a cohort study of south Brazil. AB - BACKGROUND: Adolescent mothers may have an inaccurate perception and awareness of dental trauma occurrence in children, which may influence whether or not they seek treatment. OBJECTIVE: This study evaluated maternal perception of traumatic dental injury (TDI) occurrence and related factors in children, 24-36 months of age, of adolescent mothers from a cohort in the city of Pelotas/RS, Brazil. METHODS: Clinical data from 508 children were collected through physical examination; demographic variables (including socio-economic status) and maternal perception of trauma occurrence were collected through interviews with the children's mothers. Statistical analysis was performed using STATA 12.0. RESULTS: The prevalence of dental trauma was 12.6% (64). A total of 291 (57.9%) mothers reported that their child had hit his or her teeth/mouth at least once. Only 69 (24.8%) mothers who perceived a TDI sought care. The maternal perception of dental trauma experienced by children showed no relationship with diagnosis on clinical examination. Enamel fracture was the most prevalent type of trauma (71.6%), and the maxillary central incisors were the teeth most affected. CONCLUSIONS: Owing to lack of awareness about TDI, the adolescent mothers in this study sample did not seek treatment for their children. Awareness campaigns for parents and caregivers about the possible consequences of TDI and the importance of follow up after dental trauma are required. PMID- 26818918 TI - Eco-friendly streamlined process for sporopollenin exine capsule extraction. AB - Sporopollenin exine capsules (SECs) extracted from Lycopodium clavatum spores are an attractive biomaterial possessing a highly robust structure suitable for microencapsulation strategies. Despite several decades of research into SEC extraction methods, the protocols commonly used for L. clavatum still entail processing with both alkaline and acidolysis steps at temperatures up to 180 degrees C and lasting up to 7 days. Herein, we demonstrate a significantly streamlined processing regimen, which indicates that much lower temperatures and processing durations can be used without alkaline lysis. By employing CHN elemental analysis, scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and dynamic image particle analysis (DIPA), the optimum conditions for L. clavatum SEC processing were determined to include 30 hours acidolysis at 70 degrees C without alkaline lysis. Extending these findings to proof-of-concept encapsulation studies, we further demonstrate that our SECs are able to achieve a loading of 0.170 +/- 0.01 g BSA per 1 g SECs by vacuum-assisted loading. Taken together, our streamlined processing method and corresponding characterization of SECs provides important insights for the development of applications including drug delivery, cosmetics, personal care products, and foods. PMID- 26818919 TI - Extending the Acute Care Surgery Paradigm to Global Surgery. PMID- 26818920 TI - A Functional Polymorphism (rs2494752) in the AKT1 Promoter Region and Gastric Adenocarcinoma Risk in an Eastern Chinese Population. AB - AKT is an important signal transduction protein that plays a crucial role in cancer development. Therefore, we evaluated associations between single nucleotide polymorphisms (SNPs) in the AKT promoter region and gastric cancer (GCa) risk in a case-control study of 1,110 GCa patients and 1,114 matched cancer free controls. We genotyped five SNPs (AKT1 rs2494750G >C, AKT1 rs2494752A >G, AKT1 rs10138227C >T, AKT2 rs7254617G>A and AKT2 rs2304186G >T) located in the 5' upstream regulatory, first intron or promoter regions. In the logistic regression analysis, a significantly elevated GCa risk was associated with the rs2494752 AG/GG variant genotypes (adjusted odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.02-1.42) under a dominant genetic model, and this risk was more evident in subgroups of ever drinkers. The luciferase reporter assay showed that the rs2494752 G allele significantly increased luciferase activity. Our results suggest that the potentially functional AKT1 rs2494752 SNP may affect GCa susceptibility, likely by modulating the AKT1 promoter transcriptional activity. Larger, independent studies are warranted to validate our findings. PMID- 26818921 TI - Nondipping pattern and carotid atherosclerosis: a systematic review and meta analysis. AB - Evidence on the association of nondipping pattern with carotid atherosclerosis is scarce. We performed a meta-analysis in order to provide comprehensive information on subclinical carotid alterations in nondipping as compared with dipping individuals. A computerized search was performed using PubMed, OVID, EMBASE and Cochrane library databases from 1 January 1990 up to 31 March 2015. Full articles providing data on carotid intima-media thickness (IMT) and plaque in nondipping and dipping individuals, as assessed by ultrasonography, were analyzed. A total of 2753 adult individuals (1003 nondipping and 1750 dipping) included in 13 studies were considered. Common carotid IMT was higher in nondipping than in dipping individuals [807 +/- 36 MUm vs. 746 +/- 28 MUm, standard means difference, SMD: 0.37 +/- 0.09, confidence interval (CI): 0.19 0.56, P < 0.01]. From data on plaque prevalence provided by five studies, the odds ratio for carotid plaques resulted 67% higher in nondipping (95% CI: 1.26 2.21, P < 0.01) than in dipping individuals. Our findings support an association between nondipping pattern and increased risk of subclinical carotid alterations. In a practical perspective, the present meta-analysis reinforces the view that an effective blood pressure control over the entire 24-h period, in particular at night, may prevent the progression of vascular damage associated with nondipping phenotype. PMID- 26818922 TI - Comorbidity of depression and anxiety disorders in patients with hypertension. PMID- 26818923 TI - Albuminuria: the kidney message on cardiovascular health. PMID- 26818924 TI - Antihypertensive agents and the risk of breast cancer in women aged 55 years and older: a nested case-control study. AB - OBJECTIVE: The study aimed to investigate the association of long-term use of different antihypertensive agents with incident breast cancer. METHODS: A total of 794 ,533 women aged at least 55 years were identified from Taiwan National Health Insurance claims database during 2001-2011. As of 31 December 2011, incident breast cancer patients were included as cases, and 1 : 4 age-matched controls were selected by risk-set sampling scheme. Logistic regression models were applied to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer incidence associated with different durations of use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta blockers, and dihydropyridine calcium channel blockers (DHP CCBs). Different restriction rules were applied to reveal the potential effects of confounding by indication. RESULTS: Among the 9397 incident breast cancer patients and 37 ,588 controls, a significantly elevated risk was found for relatively short-term use of DHP CCBs (<6 years) but not in those observed for more than 6 years. There was no association between either angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or beta-blockers use and breast cancer. Although restricting our analyses to those with any prescription of antihypertensive medications in 2001 or those with diagnosis of hypertension, there was no longer a statistically significant association between any use of DHP CCBs and breast cancer (OR: 1.21, 95% CI: 0.88-1.67 for the former, and OR: 1.71, 95% CI: 0.99-2.95 for the latter). CONCLUSION: The results demonstrated the potential effect of confounding by indication, and thus, did not suggest any association of the use of antihypertensive medication and breast cancer risk. PMID- 26818925 TI - Abstracts of the Hong Kong Urological Association Annual Scientific Meeting, 15 November 2015, Hong Kong. PMID- 26818926 TI - New Year, New Features in the Journal. PMID- 26818927 TI - Contending with Psychological Distress in Contexts with Limited Mental Health Resources: HIV-Positive Kenyan Women's Experiences. AB - This study describes the psychosocial distress experiences of HIV-positive women in Kenya. In-depth narrative interviews were conducted three times over six months between 2009 and 2010 with 54 HIV-positive women living in Kenya to explore how the women perceived psychological distress and the steps they took to find support to cope with their HIV-positive diagnosis. Thematic analysis revealed that the women described psychological distress as: physical and emotional shock, worry, and hopelessness and suicidality. The women reported receiving support to cope through spiritual connections, family and friends, others coping with HIV/AIDS, and health care agencies. This study heightens awareness of the critical value of understanding culturally relevant mental health evaluations in a limited mental health access context. PMID- 26818928 TI - Exploring the Relationships Among Level of Contact, Nature of Contact, and Mental Illness Stigma in Adolescent Girls. AB - This study explored the relationship of individuals' level of contact with someone with mental illness, and the nature of that contact, to mental illness stigma in adolescent females (N = 156). There were no significant associations among stigma and level of contact. The nature of the contact was significantly associated with stigma, such that those who knew someone who received treatment in a psychiatric facility had lower stigma, and those who attributed a deterioration of a past personal relationship to mental illness reported greater stigma. PMID- 26818929 TI - FBO Leaders' Perceptions of the Psycho-social Contexts for Rural Latinos. AB - Latinos comprise the largest minority rural population in the US, and they are often exposed to adverse social health determinants that can detrimentally affect their mental health. Guided by community-based participatory research (CBPR) principles, this study aimed to describe faith-based organizations (FBOs) leaders' perceptions of the contexts affecting the mental well-being of rural Latino immigrants and potential approaches to mental health promotion for these immigrants. This is a descriptive, qualitative arm of a larger study in which community-academic members have partnered to develop a culturally-tailored mental health promotion intervention among rural Latinos. FBO leaders (N = 15) from different denominations in North Florida were interviewed until saturation was reached. FBO leaders remarked that in addition to religiosity, which Latinos already have, more community building and involvement are necessary for the promotion of mental health. PMID- 26818930 TI - Stigma and Developmental Disabilities in Nursing Practice and Education. AB - Individuals with developmental disabilities (DD) experience stigma, discrimination, and barriers, including access to appropriate health care, that restrict their ability to be equal participants in society. In this study, underlying contexts, assumptions, and ways of acting are investigated that perpetuate inequalities and pejorative treatment toward those with disabilities. Several nurse researchers and educators suggest specific content for, or approaches to, education about DD. Critical pedagogy that employs cultural competency and a disability studies' framework to guide curriculum and course development will allow assumptions underlying common health care practices that oppress and "other" people with disabilities to be exposed and changed. PMID- 26818931 TI - "Easy But Not Simple"--Nursing Students' Descriptions of the Process of Care in a Psychiatric Context. AB - The nurse-patient interaction is the cornerstone of psychiatric care, yet the concept "mental health nursing" is difficult to describe. This article aims to address this problem through the experiences of nursing students. Online journals from 14 nursing students were analyzed using qualitative content analysis, resulting in three categories: Trusting the Trusting Relationship, Voicing the Unspoken Needs, and Balancing the Dynamics of Doing and Being. This study demonstrates that providing nursing care based on trusting relationships is not a demanding task, but it takes place in a complex environment that has a tendency to make easy things complicated. PMID- 26818932 TI - An Intervention with Physical Activity and Lifestyle Counseling Improves Health Related Quality of Life and Shows Small Improvements in Metabolic Risks in Persons with Psychosis. AB - This research studied the effects of a lifestyle intervention on health-related quality of life (HRQoL) and metabolic risk factors in persons with psychosis, using a longitudinal intervention design with a matched reference sample. In participants in the intervention group, scores on the EQ-VAS, which measured HRQoL, improved from 57.6 to 63.3 (SD = 17.8) (p = 0.05), and HDL cholesterol concentration increased from 1.03 to 1.11 (0.19) mmol/l. (p = 0.02). There was no significant change in body weight among participants. The results of this study indicate that a lifestyle intervention based on group meetings improves HRQoL in patients with psychosis and provides small improvements in metabolic risk factors. PMID- 26818933 TI - Patient Aggression in Real Time on Geriatric Inpatient Units. AB - This study focused on verbal and physical aggression against nursing staff, in real time, by elderly patients. The aggressive incidents were recorded at the end of each shift when they were more likely to be accurately remembered. Before beginning the study, nursing staff were taught how to use the Modified Overt Aggression Scale (MOAS) to identify aggressive acts. High rates of verbal and physical aggression among the elderly were observed by nurses, and data show that 75% of nursing staff experienced aggression on their shift. They either experienced aggression themselves or observed aggression on every single shift; that is at least five violent incidents in a work-week. Even if one is not the target of aggression, such observation is associated with elevated levels of stress. PMID- 26818934 TI - Immigrants and Health Status: Unknown? Distorted? PMID- 26818935 TI - Wisdom and Mental Health Nursing. PMID- 26818936 TI - Interventions for Drug-Using Offenders With Co-Occurring Mental Illness. PMID- 26818938 TI - Patient Recruitment 2.0: Become a Partner in the Patient Journey Using Digital Media. AB - We describe a digital platform, Pioneering Healthcare, designed to inform and empower people who are impacted by lung cancer. The platform enables Roche to support an online conversation with patients and caregivers about lung cancer, and about the role of lung cancer clinical studies in the development of future treatment options. This conversation is live and ongoing on the platform. It provides insights about the views and motivations of patients, and about how to better support patients pursuing treatment for life-threatening illness. We discuss the strategies used to deploy Pioneering Healthcare, and the advantages of using digital platforms for raising disease awareness, increasing patient engagement and, ultimately, for boosting patient enrollment into clinical trials. PMID- 26818937 TI - The interaction of perceived control and Gambler's fallacy in risky decision making: An fMRI study. AB - Limited recent evidence implicates the anterior/posterior cingulate (ACC/PCC) and lateral prefrontal networks as the neural substrates of risky decision-making biases such as illusions of control (IoC) and gambler's fallacy (GF). However, investigation is lacking on the dynamic interactive effect of those biases during decision making. Employing a card-guessing game that independently manipulates trial-by-trial perceived control and gamble outcome among 29 healthy female participants, we observed both IoC- and GF-type behaviors, as well as an interactive effect of previous control and previous outcome, with GF-type behaviors only following computer-selected, but not self-selected, outcomes. Imaging results implicated the ACC and left dorsolateral prefrontal cortex (DLPFC) in agency processing, and the cerebellum and right DLPFC in previous outcome processing, in accordance with past literature. Critically, the right inferior parietal lobule (IPL) exhibited significant betting-related activities to the interaction of previous control and previous outcome, showing more positive signals to previous computer-selected winning versus losing outcomes but the reverse pattern following self-selected outcomes, as well as responding to the interactive effect of control and outcome during feedback. Associations were also found between participants' behavioral sensitivity to the interactive effect of previous control and previous outcome, and right IPL signals, as well as its functional connectivity with neural networks implicated in agency and previous outcome processing. We propose that the right IPL provides the neural substrate for the interaction of perceived control and GF, through coordinating activities in the anterior and posterior cingulate cortices and working conjunctively with lateral PFC and other parietal networks. PMID- 26818939 TI - Knowledge and risk perception of oral cavity and oropharyngeal cancer among non medical university students. AB - BACKGROUND: To assess non-medical university students' knowledge and perceived risk of developing oral cavity and oropharyngeal cancer. METHODS: A cross sectional survey was conducted among non-medical students of a private Midwestern university in the United States in May 2012. Questionnaire assessed demographic information and contained 21 previously validated questions regarding knowledge and perceived risk of developing oral cavity and oropharyngeal cancer. Knowledge scale was categorized into low and high. Risk level was estimated based on smoking, drinking, and sexual habits. Bivariate associations between continuous and categorical variables were assessed using Pearson correlation and Chi-square tests, respectively. RESULTS: The response rate was 87% (100 out of 115 students approached). Eighty-one percent (81%) had low oral cavity and oropharyngeal cancer knowledge; and only 2% perceived that their oral cavity and oropharyngeal cancer risk was high. Risk perception was negatively correlated with age at sexual debut, r (64) = -0.26, p = 0.037; one-way ANOVA showed a marginally significant association between risk perception and number of sexual partners, F(4, 60) = 2.48, p = 0.05. There was no significant association between knowledge and perception of risk; however, oral cavity and oropharyngeal cancer knowledge was significantly associated with frequency of prevention of STDs (p < 0.05). Although 86% had heard about oral cavity and oropharyngeal cancer, only 18% had heard of oral mouth examination, and 7% of these reported ever having an oral cavity and oropharyngeal cancer exam. CONCLUSIONS: Oral cavity and oropharyngeal cancer knowledge and risk perception is low among this student population. Since oral cavity and oropharyngeal cancer incidence is increasingly shifting towards younger adults, interventions must be tailored to this group in order to improve prevention and control. PMID- 26818940 TI - Repeating cardiopulmonary health effects in rural North Carolina population during a second large peat wildfire. AB - BACKGROUND: Cardiovascular health effects of fine particulate matter (PM2.5) exposure from wildfire smoke are neither definitive nor consistent with PM2.5 from other air pollution sources. Non-comparability among wildfire health studies limits research conclusions. METHODS: We examined cardiovascular and respiratory health outcomes related to peat wildfire smoke exposure in a population where strong associations were previously reported for the 2008 Evans Road peat wildfire. We conducted a population-based epidemiologic investigation of associations between daily county-level modeled wildfire PM2.5 and cardiopulmonary emergency department (ED) visits during the 2011 Pains Bay wildfire in eastern North Carolina. We estimated changes in the relative risk cumulative over 0-2 lagged days of wildfire PM2.5 exposure using a quasi-Poisson regression model adjusted for weather, weekends, and poverty. RESULTS: Relative risk associated with a 10 MUg/m(3) increase in 24-h PM2.5 was significantly elevated in adults for respiratory/other chest symptoms 1.06 (1.00-1.13), upper respiratory infections 1.13 (1.05-1.22), hypertension 1.05 (1.00-1.09) and 'all cause' cardiac outcomes 1.06 (1.00-1.13) and in youth for respiratory/other chest symptoms 1.18 (1.06-1.33), upper respiratory infections 1.14 (1.04-1.24) and 'all cause' respiratory conditions 1.09 (1.01-1.17). CONCLUSIONS: Our results replicate evidence for increased risk of cardiovascular outcomes from wildfire PM2.5 and suggest that cardiovascular health should be considered when evaluating the public health burden of wildfire smoke. PMID- 26818941 TI - Strategies to estimate the characteristics of 24-hour IOP curves of treated glaucoma patients during office hours. AB - BACKGROUND: It is known that office-hour measurements might not adequately estimate IOP mean, peaks and fluctuations in healthy subjects. The purpose of the present study is to verify whether office-hour measurements in patients in different body positions can estimate the characteristics of 24-hour intraocular pressure (IOP) in treated POAG patients. METHODS: The 24-hour IOP curves of 70 eyes of 70 caucasian patients with treated glaucoma were analyzed. Measurements were taken at 9 AM; 12, 3, 6, and 9 PM; and 12, 3, and 6 AM, both in the supine (TonoPen XL) and sitting (Goldmann tonometer) positions. The ability of five strategies to estimate IOP mean, peak and fluctuation was evaluated. Each method was analyzed both with regression of the estimate error on the real value and with "hit or miss" analysis. RESULTS: The least biased estimate of the Peak IOP was obtained using measurements from both supine and sitting positions, also yielding the highest rate of correct predictions (which was significantly different from 3 of the remaining 4 strategies proposed, p < 0.05). Strategies obtained from the combination of supine, sitting and peak measurements resulted to be least biased for the Mean IOP and the IOP Fluctuation estimate, but all strategies were not found significantly different in terms of correct prediction rate (the only significant difference being between the two strategies based on sitting or supine measurements only, with the former being the one with the highest correct prediction rate). CONCLUSIONS: The results of this study remark the concept that IOP is a dynamic parameter and that intensive measurement is helpful in determining its characteristics. All office-hour strategies showed a very poor performance of in correctly predicting the considered parameters within the thresholds used in this paper, all scoring a correct prediction rate below 52%. PMID- 26818942 TI - Successful angioplasty during pregnancy for renal artery stenosis. AB - Renal artery stenosis can be diagnosed during pregnancy and treated at the same time. A 30-year-old woman had a sudden, severe but asymptomatic hypertensive crisis at 21 weeks of gestation. The diagnosis of renal artery stenosis suspected on Doppler ultrasonography was confirmed and treated by renal angioplasty, which reduced her blood pressure. At 27 weeks of gestation, her blood pressure increased again, associated with significant proteinuria, suggesting pre eclampsia. A cesarean section was performed giving birth to a healthy 940-g child. Renal artery stenosis should be considered when sudden and early-onset hypertension appears during pregnancy. PMID- 26818943 TI - The three waves in implementation of facility-based kangaroo mother care: a multi country case study from Asia. AB - BACKGROUND: Kangaroo mother care has been highlighted as an effective intervention package to address high neonatal mortality pertaining to preterm births and low birth weight. However, KMC uptake and service coverage have not progressed well in many countries. The aim of this case study was to understand the institutionalisation processes of facility-based KMC services in three Asian countries (India, Indonesia and the Philippines) and the reasons for the slow uptake of KMC in these countries. METHODS: Three main data sources were available: background documents providing insight in the state of implementation of KMC in the three countries; visits to a selection of health facilities to gauge their progress with KMC implementation; and data from interviews and meetings with key stakeholders. RESULTS: The establishment of KMC services at individual facilities began many years before official prioritisation for scale up. Three major themes were identified: pioneers of facility-based KMC; patterns of KMC knowledge and skills dissemination; and uptake and expansion of KMC services in relation to global trends and national policies. Pioneers of facility based KMC were introduced to the concept in the 1990s and established the practice in a few individual tertiary or teaching hospitals, without further spread. A training method beneficial to the initial establishment of KMC services in a country was to send institutional health-professional teams to learn abroad, notably in Colombia. Further in-country cascading took place afterwards and still later on KMC was integrated into newborn and obstetric care programs. The patchy uptake and expansion of KMC services took place in three phases aligned with global trends of the time: the pioneer phase with individual champions while the global focus was on child survival (1998-2006); the newborn-care phase (2007 2012); and lastly the current phase where small babies are also included in action plans. CONCLUSIONS: This paper illustrates the complexities of implementing a new healthcare intervention. Although preterm care is currently in the limelight, clear and concerted country-led KMC scale-up strategies with associated operational plans and budgets are essential for successful scale-up. PMID- 26818945 TI - Cryptosporidium galli and novel Cryptosporidium avian genotype VI in North American red-winged blackbirds (Agelaius phoeniceus). AB - Proventriculus and intestinal samples from 70 North American red-winged blackbirds (Agelaius phoeniceus; order Passeriformes) were examined for the presence of Cryptosporidium by PCR amplification and sequence analysis of the 18S ribosomal RNA (18S rRNA), actin, and 70-kDa heat shock protein (HSP70) genes. Twelve birds (17.1 %) were positive for the Cryptosporidium 18S rRNA gene: six birds were positive at the proventriculus site only and six birds were positive at the proventriculus and intestinal sites. Sequence analysis of the 18S rRNA, actin and HSP70 genes showed the presence of the gastric species Cryptosporidium galli in a single proventriculus sample and a closely related genotype, which we have named Cryptosporidium avian genotype VI, in all other positive samples. These findings contribute to our understanding of Cryptosporidium diversification in passerines, the largest avian order. PMID- 26818944 TI - Giardia duodenalis and Giardia enterica in children: first evidence of assemblages A and B in Eastern Slovakia. AB - For an overview on the occurrence of Giardia assemblages in children in Eastern Slovakia, we examined 259 faecal samples of children from the segregated settlement in Medzev, 30 samples of children from the orphanage in Medzev and 40 samples of children with autism from the Special Elementary School in Kosice. Thirty-eight samples (14.67 %) from the segregated settlement, 19 samples (63.33 %) from the orphanage and two samples (5.0 %) from the Special Elementary School were positive for Giardia by flotation. The initial microscopic diagnostics were completed by the genotyping of the triosephosphate isomerase-gene loci (tpi genes) which revealed the existence of two Giardia assemblages in Slovak population, namely Giardia duodenalis (assemblage A) and Giardia enterica (assemblage B). These results represent the first evidence of A and B assemblages in children in Slovakia. Epidemiological significance and the impact on the public health of Giardia infection are highlighted. PMID- 26818946 TI - Contraceptive use, knowledge, attitude, perceptions and sexual behavior among female University students in Uganda: a cross-sectional survey. AB - BACKGROUND: In Uganda, the risk of unintended pregnancies and unsafe abortions remains high due to relatively low contraceptive use. There is paucity of data on knowledge, attitudes, perceptions and practices towards modern contraceptives and, sexual and reproductive health especially among the young female university students. METHODS: A survey was conducted at Makerere University main campus in Kampala, Uganda during April 2014. A team of well-trained and experienced research assistants interviewed female undergraduate students who provided data on socio-demographic characteristics, knowledge, perceptions and attitudes and use of contraceptives, as well as other sexual and reproductive health practices. Users of any contraceptive method in the past 12 months were coded as '1' and none users as '0'. The prevalence of contraceptive use was determined as the number of users divided by all female participants. Prevalence ratios (PRs) with their corresponding 95 % confidence intervals were used as measures of association between contraceptive use and associated factors. The PRs were obtained via a modified Poisson regression model using a generalized linear model with Poisson as family and a log link without an offset but including robust standard errors. All analyses were conducted with Stata version 13. RESULTS: A total of 1,008 females responded to the survey; median (IQR) age was 21(20, 21) years, 38.6% in year 2 of study, and nearly three quarters (72.3%) were of Christian faith. Knowledge of any contraceptives was almost universal (99.6%) but only 22.1% knew about female condoms. Perceived acceptability of contraceptive use at the university (93%) or being beneficial to male partners too (97.8%) were high. Nearly 70% had ever engaged in sexual intercourse and 62.1% reported sexual intercourse in the past 12 months. Overall, 46.6% reported current contraceptive use, with male condoms (34.5%) being the commonest methods. Factors associated with higher contraceptive use were being in year 2, consensual union or perception that contraceptives are for females only. However, being evangelical/SDA or perception that contraceptive use is wrong was associated with lower contraceptive use. Overall, 9% reported ever being pregnant, 2% were pregnant at the time of the survey and a third (33.8%) knew of a pregnant friend. About 40% of ever pregnant respondents reported ever trying to terminate the pregnancy. CONCLUSIONS: Knowledge, perceived acceptability and benefits of contraceptive use were nearly universal, but contraceptive use was suboptimal in this setting. Ever trying to terminate a pregnancy was common and a clear indicator of unintended pregnancies. PMID- 26818948 TI - From photon to signal in phytochromes: similarities and differences between prokaryotic and plant phytochromes. AB - Phytochromes represent a diverse family of red/far-red-light absorbing chromoproteins which are widespread across plants, cyanobacteria, non photosynthetic bacteria, and more. Phytochromes play key roles in regulating physiological activities in response to light, a critical element in the acclimatization to the environment. The discovery of prokaryotic phytochromes facilitated structural studies which deepened our understanding on the general mechanisms of phytochrome action. An extrapolation of this information to plant phytochromes is justified for universally conserved functional aspects, but it is also true that there are many aspects which are unique to plant phytochromes. Here I summarize some structural studies carried out to date on both prokaryotic and plant phytochromes. I also attempt to identify aspects which are common or unique to plant and prokaryotic phytochromes. Phytochrome themselves, as well as the downstream signaling pathway in plants are more complex than in their prokaryotic counterparts. Thus many structural and functional aspects of plant phytochrome remain unresolved. PMID- 26818949 TI - Physiological and biochemical responses of the forage legume Trifolium alexandrinum to different saline conditions and nitrogen levels. AB - Salinity stress reduces plant productivity, but low levels of salinity often increase plant growth rates in some species. We herein describe the effects of salinity on plant growth while focusing on nitrogen use. We treated Trifolium alexandrinum with two nitrogen concentrations and salinity levels and determined growth rates, mineral concentrations, nitrogen use efficiency, photosynthesis rates, and nitrate reductase (NR, E.C. 1.6.6.1) and glutamine synthetase (GS, EC 6.3.1.2) activities. The T. alexandrinum growth rate increased following treatment with 100 mM NaCl in low nitrogen (LN) and high nitrogen (HN) conditions. Salt treatment also increased root volume, intrinsic water use efficiency, and nitrogen use efficiency in LN and HN conditions. These changes likely contributed to higher biomass production. Salinity also increased accumulations of sodium, chloride, and phosphate, but decreased potassium and calcium levels and total nitrogen concentrations in all plant organs independently of the available nitrogen level. However, the effect of salt treatment on magnesium and nitrate concentrations in photosynthetic organs depended on nitrogen levels. Salt treatment reduced photosynthesis rates in LN and HN conditions because of inhibited stomatal conductance. The effects of salinity on leaf NR and GS activities depended on nitrogen levels, with activities increasing in LN conditions. In saline conditions, LN availability resulted in optimal growth because of low chloride accumulation and increases in total nitrogen concentrations, nitrogen use efficiency, and NR and GS activities in photosynthetic organs. Therefore, T. alexandrinum is a legume forage crop that can be cultivated in low-saline soils where nitrogen availability is limited. PMID- 26818950 TI - In situ characterization of the decomposition behavior of Mg(BH4)2 by X-ray Raman scattering spectroscopy. AB - We present an in situ study of the thermal decomposition of Mg(BH4)2 in a hydrogen atmosphere of up to 4 bar and up to 500 degrees C using X-ray Raman scattering spectroscopy at the boron K-edge and the magnesium L2,3-edges. The combination of the fingerprinting analysis of both edges yields detailed quantitative information on the reaction products during decomposition, an issue of crucial importance in determining whether Mg(BH4)2 can be used as a next generation hydrogen storage material. This work reveals the formation of reaction intermediate(s) at 300 degrees C, accompanied by a significant hydrogen release without the occurrence of stable boron compounds such as amorphous boron or MgB12H12. At temperatures between 300 degrees C and 400 degrees C, further hydrogen release proceeds via the formation of higher boranes and crystalline MgH2. Above 400 degrees C, decomposition into the constituting elements takes place. Therefore, at moderate temperatures, Mg(BH4)2 is shown to be a promising high-density hydrogen storage material with great potential for reversible energy storage applications. PMID- 26818947 TI - Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes. AB - Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P<5 * 10(-8)), rs1116357 near CCDC85A, rs147538848 in FAM60A, rs1575972 near DMRTA1, rs9309245 near ASB3, rs67156297 near ATP8B2, rs7107784 near MIR4686 and rs67839313 near INAFM2. Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P<0.007). These results indicate that expansion of single ethnic GWAS is still useful to identify novel susceptibility loci to complex traits not only for ethnicity-specific loci but also for common loci across different ethnicities. PMID- 26818952 TI - Power estimation and sample size determination for replication studies of genome wide association studies. AB - BACKGROUND: Replication study is a commonly used verification method to filter out false positives in genome-wide association studies (GWAS). If an association can be confirmed in a replication study, it will have a high confidence to be true positive. To design a replication study, traditional approaches calculate power by treating replication study as another independent primary study. These approaches do not use the information given by primary study. Besides, they need to specify a minimum detectable effect size, which may be subjective. One may think to replace the minimum effect size with the observed effect sizes in the power calculation. However, this approach will make the designed replication study underpowered since we are only interested in the positive associations from the primary study and the problem of the "winner's curse" will occur. RESULTS: An Empirical Bayes (EB) based method is proposed to estimate the power of replication study for each association. The corresponding credible interval is estimated in the proposed approach. Simulation experiments show that our method is better than other plug-in based estimators in terms of overcoming the winner's curse and providing higher estimation accuracy. The coverage probability of given credible interval is well-calibrated in the simulation experiments. Weighted average method is used to estimate the average power of all underlying true associations. This is used to determine the sample size of replication study. Sample sizes are estimated on 6 diseases from Wellcome Trust Case Control Consortium (WTCCC) using our method. They are higher than sample sizes estimated by plugging observed effect sizes in power calculation. CONCLUSIONS: Our new method can objectively determine replication study's sample size by using information extracted from primary study. Also the winner's curse is alleviated. Thus, it is a better choice when designing replication studies of GWAS. The R package is available at: http://bioinformatics.ust.hk/RPower.html . PMID- 26818951 TI - Activation of phagocytic activity in astrocytes by reduced expression of the inflammasome component ASC and its implication in a mouse model of Alzheimer disease. AB - BACKGROUND: The proinflammatory cytokine interleukin-1beta (IL-1beta) is overexpressed in Alzheimer disease (AD) as a key regulator of neuroinflammation. Amyloid-beta (Abeta) peptide triggers activation of inflammasomes, protein complexes responsible for IL-1beta maturation in microglial cells. Downregulation of NALP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome has been shown to decrease amyloid load and rescue cognitive deficits in a mouse model of AD. Whereas activation of inflammasome in microglial cells has been described in AD, no data are currently available concerning activation of inflammasome in astrocytes, although they are involved in inflammatory response and phagocytosis. Here, by targeting the inflammasome adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD domain), we investigated the influence of activation of the inflammasome on the phagocytic activity of astrocytes. METHODS: We used an ASC knockout mouse model, as ASC is a central protein in the inflammasome, acting as an adaptor and stabilizer of the complex and thus critical for its activation. Lipopolysaccharide (LPS)-primed primary cultures of astrocytes from newborn mice were utilized to evaluate Abeta-induced inflammasome activation by measuring IL-1beta release by ECLIA (electro-chemiluminescence immunoassay). Phagocytosis efficiency was measured by incorporation of bioparticles, and the release of the chemokine CCL3 (C-C motif ligand 3) was measured by ECLIA. ASC mice were crossbred with 5xFAD (familial Alzheimer disease) mice and tested for spatial reference memory using the Morris water maze (MWM) at 7-8 months of age. Amyloid load and CCL3 were quantified by thioflavine S staining and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. RESULTS: Cultured astrocytes primed with LPS and treated with Abeta showed an ASC-dependent production of IL-1beta resulting from inflammasome activation mediated by Abeta phagocytosis and cathepsin B enzymatic activity. ASC+/- astrocytes displayed a higher phagocytic activity as compared to ASC+/+ and ASC -/- cells, resulting from a higher release of the chemokine CCL3. A significant decrease in amyloid load was measured in the brain of 7-8-month-old 5xFAD mice carrying the ASC +/- genotype, correlated with an increase in CCL3 gene expression. In addition, the ASC +/- genotype rescued spatial reference memory deficits observed in 5xFAD mice. CONCLUSIONS: Our results demonstrate that Abeta is able to activate astrocytic inflammasome. Downregulation of inflammasome activity increases phagocytosis in astrocytes due to the release of CCL3. This could explain why downregulation of inflammasome activity decreases amyloid load and rescues memory deficits in a mouse model of AD. PMID- 26818953 TI - Standardization of Hemagglutination Inhibition Assay for Influenza Serology Allows for High Reproducibility between Laboratories. AB - Standardization of the hemagglutination inhibition (HAI) assay for influenza serology is challenging. Poor reproducibility of HAI results from one laboratory to another is widely cited, limiting comparisons between candidate vaccines in different clinical trials and posing challenges for licensing authorities. In this study, we standardized HAI assay materials, methods, and interpretive criteria across five geographically dispersed laboratories of a multidisciplinary influenza research network and then evaluated intralaboratory and interlaboratory variations in HAI titers by repeatedly testing standardized panels of human serum samples. Duplicate precision and reproducibility from comparisons between assays within laboratories were 99.8% (99.2% to 100%) and 98.0% (93.3% to 100%), respectively. The results for 98.9% (95% to 100%) of the samples were within 2 fold of all-laboratory consensus titers, and the results for 94.3% (85% to 100%) of the samples were within 2-fold of our reference laboratory data. Low-titer samples showed the greatest variability in comparisons between assays and between sites. Classification of seroprotection (titer >= 40) was accurate in 93.6% or 89.5% of cases in comparison to the consensus or reference laboratory classification, respectively. This study showed that with carefully chosen standardization processes, high reproducibility of HAI results between laboratories is indeed achievable. PMID- 26818954 TI - Progress toward a Respiratory Syncytial Virus Vaccine. AB - In accompanying papers (P. L. Acosta, M. T. Caballero, and F. P. Polack, Clin Vaccine Immunol 23:189-195, 2016, http://dx.doi.org/10.1128/CVI.00609-15; M. Vissers, I. M. L. Ahout, M. I. de Jonge, and G. Ferwerda, Clin Vaccine Immunol 23:243-245, 2016, http://dx.doi.org/10.1128/CVI.00590-15) in this issue of Clinical and Vaccine Immunology, the history of and immune mechanisms underlying vaccine-enhanced respiratory syncytial virus (RSV) disease and of investigations of mucosal antibodies and their association with viral load in RSV-infected children, respectively, are described. This commentary discusses RSV vaccine candidates, target populations, and the challenges associated with achieving a safe and effective vaccine. PMID- 26818956 TI - First experience using cultured epidermal autografts in Taiwan for burn victims of the Formosa Fun Coast Water Park explosion, as part of Japanese medical assistance. AB - On June 27, 2015, a flammable starch-based powder exploded at Formosa Fun Coast in Taipei, Taiwan, injuring 499 people, and more than 200 people were in critical condition with severe burns. Although a cultured epidermal autograft (CEA) was not approved or used in clinical practice, the Taiwan Food and Drug Administration requested a Japanese CEA manufacturer to donate CEA for the burn victims as part of international medical assistance. The authors cooperated in this project and participated in the patient selection, wound bed management for CEA, and technical assistance for CEA use. Here, we provide an overview of the project. Nine patients were enrolled, and two patients were excluded from the skin biopsy; seven skin biopsies were collected approximately 1 month after the disaster. The average TBSA% burned was 81.0%, and the mean age was 20.1 years. CEA was grafted in five patients; wound closure had been obtained in one patient, and one patient was severely ill at the time of grafting. The CEA was combined with a wide split auto mesh graft or patch graft. The mean re-epithelization rate at 4 weeks after the grafting was 84.2% by patient, and all of the patients survived. Although this project had many obstacles to overcome, CEA grafting was successful and contributed to wound closure and survival. PMID- 26818955 TI - Fires in refugee and displaced persons settlements: The current situation and opportunities to improve fire prevention and control. AB - INTRODUCTION: We aimed to describe the burden of fires in displaced persons settlements and identify interventions/innovations that might address gaps in current humanitarian guidelines. METHODS: We performed a systematic review of: (i) academic and non-academic literature databases; and (ii) guidelines from leading humanitarian agencies/initiatives regarding fire prevention/control. RESULTS: Of the 1521 records retrieved, 131 reports described settlement fires in 31 hosting countries since 1990. These incidents resulted in 487 deaths, 790 burn injuries, displacement of 382,486 individuals and destruction of 50,509 shelters. There was a 25-fold increase in the rate of settlement fires from 1990 to 2015 (0.002-0.051 per 100,000 refugees, respectively). Only 4 of the 15 leading humanitarian agencies provided recommendations about fire prevention/control strategies. Potentially useful interventions/innovations included safer stoves (e.g. solar cookers) and fire retardant shelter materials. CONCLUSION: The large and increasing number of fires in displaced persons settlements highlights the need to redress gaps in humanitarian fire prevention/control guidelines. The way forward includes: (i) developing consensus among aid agencies regarding fire prevention/control strategies; (ii) evaluating the impact of interventions/innovations on the burden of fires; and (iii) engaging agencies in a broader discussion about protecting camp residents from armed groups. PMID- 26818957 TI - Correcting a prevalent misunderstanding of burns. PMID- 26818959 TI - A novel technique to prevent damage to the inflation tube of the cuffed endotracheal tube during air-Q guided intubation. PMID- 26818960 TI - Differences in toxicity and outcome associated with circadian variations between patients undergoing daytime and evening radiotherapy for prostate adenocarcinoma. AB - This retrospective study tested the hypothesis that disease control and treatment related toxicity in patients undergoing high-dose radiotherapy (HDRT) for prostate cancer varies in a circadian manner. Patients with localized prostate adenocarcinoma receiving HDRT (median 78 Gy) to the prostate and involved seminal vesicle(s) without elective pelvic irradiation were divided into a daytime treatment (before 5 PM) group (n = 267) and evening treatment (after 5 PM) group (n = 142). Biochemical failure (Phoenix definition), acute and late gastrointestinal (GI) and genitourinary toxicities (Common Terminology Criteria for Adverse Events version 4), biochemical failure-free survival (BFFS) and freedom from late toxicity were assessed. Analyses were performed by binary logistic regression and Cox proportional hazard regression. The median follow-up was 68 months, and 75% of patients were >=70 years old. Evening HDRT was significantly associated with worse freedom from >=grade 2 late GI complications (hazard ratio = 2.96; p < 0.001). The detrimental effect of evening HDRT was significant in patients older than 70 years old (p < 0.001) but not in younger patients (p = 0.63). In a subgroup of propensity score-matched cohort with T2b-T3 disease (n = 154), the 5-year BFFS was worse in the evening group than the daytime group (72% vs. 85%, hazard ratio = 1.95, p = 0.05). Our study indicates that evening HDRT may lead to more GI complications, especially in older patients, and worse BFFS in patients with T2b-T3 disease. PMID- 26818958 TI - 3,39-Diindolylmethane Ameliorates Staphylococcal Enterotoxin B-Induced Acute Lung Injury through Alterations in the Expression of MicroRNA that Target Apoptosis and Cell-Cycle Arrest in Activated T Cells. AB - 3,39-Diindolylmethane (DIM), a natural indole found in cruciferous vegetables, has significant anti-cancer and anti-inflammatory properties. In this current study, we investigated the effects of DIM on acute lung injury (ALI) induced by exposure to staphylococcal enterotoxin B (SEB). We found that pretreatment of mice with DIM led to attenuation of SEB-induced inflammation in the lungs, vascular leak, and IFN-g secretion. Additionally, DIM could induce cell-cycle arrest and cell death in SEB-activated T cells in a concentration-dependent manner. Interestingly, microRNA (miRNA) microarray analysis uncovered an altered miRNA profile in lung-infiltrating mononuclear cells after DIM treatment of SEB exposed mice. Moreover, computational analysis of miRNA gene targets and regulation networks indicated that DIM alters miRNA in the cell death and cell cycle progression pathways. Specifically, DIM treatment significantly downregulated several miRNA and a correlative increase associated gene targets. Furthermore, overexpression and inhibition studies demonstrated that DIM-induced cell death, at least in part, used miR-222. Collectively, these studies demonstrate for the first time that DIM treatment attenuates SEB-induced ALI and may do so through the induction of microRNAs that promote apoptosis and cell cycle arrest in SEB-activated T cells. PMID- 26818961 TI - An ethnographic investigation of the maternity healthcare experience of immigrants in rural and urban Alberta, Canada. AB - BACKGROUND: Canada is among the top immigrant-receiving nations in the world. Immigrant populations may face structural and individual barriers in the access to and navigation of healthcare services in a new country. The aims of the study were to (1) generate new understanding of the processes that perpetuate immigrant disadvantages in maternity healthcare, and (2) devise potential interventions that might improve maternity experiences and outcomes for immigrant women in Canada. METHODS: The study utilized a qualitative research approach that focused on ethnographic research design and data analysis contextualized within theories of organizational behaviour and critical realism. Data were collected over 2.5 years using focus groups and in-depth semistructured interviews with immigrant women (n = 34), healthcare providers (n = 29), and social service providers (n = 23) in a Canadian province. Purposive samples of each subgroup were generated, and recruitment and data collection - including interpretation and verification of translations - were facilitated through the hiring of community researchers and collaborations with key informants. RESULTS: The findings indicate that (a) communication difficulties, (b) lack of information, (c) lack of social support (isolation), (d) cultural beliefs, e) inadequate healthcare services, and (f) cost of medicine/services represent potential barriers to the access to and navigation of maternity services by immigrant women in Canada. Having successfully accessed and navigated services, immigrant women often face additional challenges that influence their level of satisfaction and quality of care, such as lack of understanding of the informed consent process, lack of regard by professionals for confidential patient information, short consultation times, short hospital stays, perceived discrimination/stereotyping, and culture shock. CONCLUSIONS: Although health service organizations and policies strive for universality and equality in service provision, personal and organizational barriers can limit care access, adequacy, and acceptability for immigrant women. A holistic healthcare approach must include health informational packages available in different languages/media. Health care professionals who care for diverse populations must be provided with training in cultural competence, and monitoring and evaluation programs to ameliorate personal and systemic discrimination. PMID- 26818962 TI - Missing value imputation for microRNA expression data by using a GO-based similarity measure. AB - BACKGROUND: Missing values are commonly present in microarray data profiles. Instead of discarding genes or samples with incomplete expression level, missing values need to be properly imputed for accurate data analysis. The imputation methods can be roughly categorized as expression level-based and domain knowledge based. The first type of methods only rely on expression data without the help of external data sources, while the second type incorporates available domain knowledge into expression data to improve imputation accuracy. In recent years, microRNA (miRNA) microarray has been largely developed and used for identifying miRNA biomarkers in complex human disease studies. Similar to mRNA profiles, miRNA expression profiles with missing values can be treated with the existing imputation methods. However, the domain knowledge-based methods are hard to be applied due to the lack of direct functional annotation for miRNAs. With the rapid accumulation of miRNA microarray data, it is increasingly needed to develop domain knowledge-based imputation algorithms specific to miRNA expression profiles to improve the quality of miRNA data analysis. RESULTS: We connect miRNAs with domain knowledge of Gene Ontology (GO) via their target genes, and define miRNA functional similarity based on the semantic similarity of GO terms in GO graphs. A new measure combining miRNA functional similarity and expression similarity is used in the imputation of missing values. The new measure is tested on two miRNA microarray datasets from breast cancer research and achieves improved performance compared with the expression-based method on both datasets. CONCLUSIONS: The experimental results demonstrate that the biological domain knowledge can benefit the estimation of missing values in miRNA profiles as well as mRNA profiles. Especially, functional similarity defined by GO terms annotated for the target genes of miRNAs can be useful complementary information for the expression-based method to improve the imputation accuracy of miRNA array data. Our method and data are available to the public upon request. PMID- 26818964 TI - Mineralisation and degradation of 2,4-dichlorophenoxyacetic acid dimethylamine salt in a biobed matrix and in topsoil. AB - BACKGROUND: Biobeds are used for on-farm bioremediation of pesticides in sprayer rinsate and from spills during sprayer filling. Using locally sourced materials from Saskatchewan, Canada, a biobed matrix was evaluated for its effectiveness for mineralising and degrading 2,4-dichlorophenoxyacetic acid dimethylamine salt (2,4-D DMA) compared with the topsoil used in the biobed matrix. RESULTS: Applying 2,4-D DMA to the biobed matrix caused a 2-3 day lag in CO2 production not observed when the herbicide was applied to topsoil. Despite the initial lag, less residual 2,4-D was measured in the biobed (0%) matrix than in the topsoil (57%) after a 28 day incubation. When the herbicide was applied 5 times to the biobed matrix, net CO2 increased immediately after each 2,4-D DMA application. Mineralisation of 2,4-D DMA was 61.9% and residual 2,4-D in the biobed matrix was 0.3% after 60 days, compared with corresponding values of 32.9 and 70.9% in topsoil. CONCLUSION: The biobed matrix enhanced the mineralisation and degradation of 2,4-D DMA, indicating the potential for successful implementation of biobeds under Canadian conditions. The biobed matrix was more effective for mineralising and degrading the herbicide compared with the topsoil used in the biobed matrix. By correcting for biobed matrix and formulation blank, CO2 evolution was a reliable indicator of 2,4-D DMA mineralisation. (c) 2016 Society of Chemical Industry. PMID- 26818963 TI - Role of single-point mutations and deletions on transition temperatures in ideal proteinogenic heteropolymer chains in the gas phase. AB - A coarse-grained statistical mechanics-based model for ideal heteropolymer proteinogenic chains of non-interacting residues is presented in terms of the size K of the chain and the set of helical propensities [Formula: see text] associated with each residue j along the chain. For this model, we provide an algorithm to compute the degeneracy tensor [Formula: see text] associated with energy level [Formula: see text] where [Formula: see text] is the number of residues with a native contact in a given conformation. From these results, we calculate the equilibrium partition function [Formula: see text] and characteristic temperature [Formula: see text] at which a transition from a low to a high entropy states is observed. The formalism is applied to analyze the effect on characteristic temperatures [Formula: see text] of single-point mutations and deletions of specific amino acids [Formula: see text] along the chain. Two probe systems are considered. First, we address the case of a random heteropolymer of size K and given helical propensities [Formula: see text] on a conformational phase space. Second, we focus our attention to a particular set of neuropentapeptides, [Met-5] and [Leu-5] enkephalins whose thermodynamic stability is a key feature on their coupling to [Formula: see text] and [Formula: see text] receptors and the triggering of biochemical responses. PMID- 26818966 TI - Editorial--February 2016. PMID- 26818965 TI - Individual Restriction Of Fine Specificity Variability In Anti-GM1 IgG Antibodies Associated With Guillain-Barre Syndrome. AB - Elevated titers of serum antibodies against GM1 ganglioside are associated with a variety of autoimmune neuropathies. Much evidence indicates these autoantibodies play a primary role in the disease processes, but the mechanism for their appearance is unclear. We studied the fine specificity of anti-GM1 antibodies of the IgG isotype present in sera from patients with Guillain-Barre syndrome (GBS), using thin-layer chromatogram-immunostaining of GM1, asialo-GM1 (GA1), GD1b and GM1-derivatives with small modifications on the oligosaccharide moiety. We were able to distinguish populations of antibodies with different fine specificity. Remarkably, individual patients presented only one or two of them, and different patients had different populations. This restriction in the variability of antibody populations suggests that the appearance of the anti-GM1 antibodies is a random process involving restricted populations of lymphocytes. With the origin of disease-associated anti-GM1 antibodies as a context, this finding could provide explanation for the "host susceptibility factor" observed in GBS following enteritis with GM1 oligosaccharide-carrying strains of Campylobacter jejuni. PMID- 26818967 TI - Active reviewers 2015. PMID- 26818968 TI - M-sequences in ophthalmic electrophysiology. AB - The aim of this review is to use the multimedia aspects of a purely digital online publication to explain and illustrate the highly capable technique of m sequences in multifocal ophthalmic electrophysiology. M-sequences have been successfully applied in clinical routines during the past 20 years. However, the underlying mathematical rationale is often daunting. These mathematical properties of m-sequences allow one not only to separate the responses from different fields but also to analyze adaptational effects and impacts of former events. By explaining the history, the formation, and the different aspects of application, a better comprehension of the technique is intended. With this review we aim to clarify the opportunities of m-sequences in order to motivate scientists to use m-sequences in their future research. PMID- 26818969 TI - Motion perception under mesopic vision. AB - Mesopic and scotopic vision extend over an illuminance range of 106. The goal of the present study was to determine the effect of decreasing light level on the underlying motion mechanism that integrates spatiotemporally separated motion signals. To accomplish this, we took advantage of the phenomenon of visual motion priming, in which the perceived direction of a directionally ambiguous test stimulus is influenced by the directional movement of a preceding priming stimulus. After terminating a drifting priming stimulus, a 180 degrees phase shifted grating was presented as a test stimulus. The priming and test stimuli were separately presented to the central and peripheral retinas, respectively. The participants judged the perceived direction of this test stimulus at various light levels from photopic to scotopic levels. We found that the effects of motion priming disappeared over 1 log unit of mesopic light levels. When the test stimulus was presented before the offset of the priming stimulus to compensate for the temporal delay in the rod pathway or when both stimuli were presented at the same location in the periphery, a motion-priming effect appeared at mesopic light levels. These results suggest that different temporal characteristics between the cone pathway and rod pathway disturb the function of the putative motion mechanism responsible for the spatiotemporal integration of motion signals, which leads to specific modulation of motion perception over a wide range of mesopic vision. PMID- 26818970 TI - Gender representation in the vision sciences: A longitudinal study. AB - Understanding the current status and historical trends of gender representation within a research field is an important component of fostering a diverse and inclusive scientific community. Here, we report on the gender representation of a large sample of the vision science research community--the attendees of the Annual Meeting of the Vision Sciences Society (VSS). Our analysis shows that the majority of scientists at all career levels in our sample are male. This imbalance is most pronounced for the senior scientists, whereas predoctoral students are nearly balanced between the genders. Historically, the gender imbalance was larger than it is at present, and it has followed a slow-but-steady trend toward gender parity over the past decade. A longitudinal analysis based on tracking individual attendees shows a larger dropout rate for female than male predoctoral trainees. However, among the trainees who continue in the vision science field after graduate school, evidence suggests that career advancement is quite similar between the genders. In an additional analysis, we found that the VSS Young Investigator awardees and the abstract review committee members reflect substantial gender imbalances, suggesting that these recognitions have yet to catch up with the greater gender balance of the rising generation of junior vision scientists. We hope that this report will encourage awareness of issues of diversity in the scientific community and further promote the development of a research field in which all talented scientists are supported to succeed. PMID- 26818971 TI - It's in the eyes: Planning precise manual actions before execution. AB - It is well-known that our eyes typically fixate those objects in a scene, with which interactions are about to unfold. During manual interactions, our eyes usually anticipate the next subgoal and thus serve top-down, goal-driven information extraction requirements, probably driven by a schema-based task representation. On the other hand, motor control research concerning object manipulations has extensively demonstrated how grasping choices are often influenced by deeper considerations about the final goal of manual interactions. Here we show that also these deeper considerations are reflected in early eye fixation behavior, significantly before the hand makes contact with the object. In this study, subjects were asked to either pretend to drink out of the presented object or to hand it over to the experimenter. The objects were presented upright or upside down, thus affording a thumb-up (prone) or a thumb down (supine) grasp. Eye fixation data show a clear anticipatory preference for the region where the index finger is going to be placed. Indeed, fixations highly correlate with the final index finger position, thus subserving the planning of the actual manual action. Moreover, eye fixations reveal several orders of manual planning: Fixation distributions do not only depend on the object orientation but also on the interaction task. These results suggest a fully embodied, bidirectional sensorimotor coupling of eye-hand coordination: The eyes help in planning and determining the actual manual object interaction, considering where to grasp the presented object in the light of the orientation and type of the presented object and the actual manual task to be accomplished with the object. PMID- 26818972 TI - Does the 'slipping slipper sign' in patients with diabetes predict the presence of retinopathy and nephropathy? AB - BACKGROUND: Previous research had noted that an affirmative response in patients with diabetes to the question 'Have you ever lost your slipper/flip-flop from your feet while walking and not realised that you have done so'? That is, the presence of the 'slipping slipper sign' (SSS) reflected the presence of severe diabetic peripheral neuropathy with a high degree of precision. The objective of the current study was to determine whether the SSS may also predict the presence of diabetic retinopathy and/or nephropathy since microvascular complications are known to cosegregate. SUBJECTS AND METHODS: Among 100 patients with diabetes, including 33 cases with the SSS and 67 controls without the SSS, data on demography, dipstick proteinuria as well as the presence and staging of diabetic retinopathy were obtained. RESULTS: The mean (SD) age of all patients was 54.6 (13.0) years, mean duration of diabetes was 12.7 (10.2) years and mean haemoglobin A1c (HbA1c) 8.42 (1.95) %; 43% were males. All 33 (100%) of the patients with SSS but only 12 (18%) of the patients without SSS were found to exhibit diabetic retinopathy, p<0.001. Among those patients with retinopathy, proliferative retinopathy was far more likely (39%) in the SSS group compared with non-SSS subjects (8%). Similarly, 15 (46%) with SSS and only 4 (6%) without SSS were found to have dipstick proteinuria. The sensitivity of the SSS for retinopathy was 73% and the specificity was 100% with a positive predictive value (PPV) of 100% and negative predictive value (NPV) of 82%. For proteinuria, both the sensitivity and specificity was 78%. CONCLUSIONS: Both diabetic retinopathy and dipstick proteinuria are strongly associated with the presence of the SSS that therefore holds potential as a tool for easier identification of this high risk group. PMID- 26818973 TI - Sunflower cataract. PMID- 26818974 TI - Tofacitinib, an oral Janus kinase inhibitor, as monotherapy or with background methotrexate, in Japanese patients with rheumatoid arthritis: an open-label, long term extension study. AB - BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Here, tofacitinib safety and efficacy data from a long-term extension study in Japanese patients are presented. METHODS: Study A3921041 was a multi-centre, open-label, long-term extension study that included Japanese patients who had participated in a prior Phase 2 or Phase 3 study of tofacitinib as monotherapy or with background methotrexate. Patients received tofacitinib 5 mg twice daily (BID) or tofacitinib 10 mg BID. Dose adjustment of tofacitinib during treatment period, and concomitant usage of disease-modifying antirheumatic drugs including methotrexate after week 12 were permitted. Primary endpoints were adverse events, laboratory parameters and vital signs. Secondary efficacy endpoints included American College of Rheumatology (ACR)20/50/70 response rates, Disease Activity Score (DAS)28-4(erythrocyte sedimentation rate (ESR))<2.6 response rate (DAS-defined remission) and Health Assessment Questionnaire Disability Index (HAQ-DI) score. Safety and efficacy data were assessed throughout the study. RESULTS: A total of 486 patients were recruited and treated (1439.9 patient-years of exposure). 308 patients completed the study. Median (range) duration of treatment in this extension study was 1185 (5-2016) days. 476 patients (97.9 %) experienced adverse events; the majority of which (97.8 %) were of mild or moderate severity. The two most common treatment-emergent adverse events were nasopharyngitis (n = 293, 60.3 %) and herpes zoster (n = 94, 19.3 %). For all tofacitinib-treated patients, the incidence rate (patients with events per 100 patient-years) was 10.7 for serious adverse events, 3.3 for serious infections, 7.4 for herpes zoster (serious and non-serious) and 1.2 for malignancies (excluding non-melanoma skin cancer). Mean changes from baseline (start of the index study) in laboratory parameters were consistent with those seen in previously reported studies of tofacitinib. ACR20/50/70 response rates, DAS-defined remission rates and HAQ-DI scores were sustained through to study completion. CONCLUSIONS: Tofacitinib (with or without background methotrexate) demonstrated a stable safety profile and sustained efficacy in Japanese patients with active rheumatoid arthritis. The risk of herpes zoster appears to be higher in Japanese patients treated with tofacitinib than in the global population. TRIAL REGISTRATION: Clinicaltrials.gov NCT00661661 . Registered 7 February 2008. PMID- 26818975 TI - Comprehensive identification of sexually dimorphic genes in diverse cattle tissues using RNA-seq. AB - BACKGROUND: Molecular mechanisms associated with sexual dimorphism in cattle have not been well elucidated. Furthermore, as recent studies have implied that gene expression patterns are highly tissue specific, it is essential to investigate gene expression in a variety of tissues using RNA-seq. Here, we employed and compared two statistical methods, a simple two group test and Analysis of deviance (ANODEV), in order to investigate bovine sexually dimorphic genes in 40 RNA-seq samples distributed across two factors: sex and tissue. RESULTS: As a result, we detected 752 sexually dimorphic genes across tissues from two statistical approaches and identified strong tissue-specific patterns of gene expression. Additionally, significantly detected sex-related genes shared between two mammal species (cattle and rat) were identified using qRT-PCR. CONCLUSIONS: Results of our analyses reveal that sexual dimorphism of metabolic tissues and pituitary gland in cattle involves various biological processes. Several differentially expressed genes between sexes in cattle and rat species are shared, but show tissue-specific patterns. Finally, we concluded that two distinct statistical approaches have their advantages and disadvantages in RNA seq studies investigating multiple tissues. PMID- 26818976 TI - miR-23a, miR-146a and miR-301a confer predisposition to Vogt-Koyanagi-Harada syndrome but not to Behcet's disease. AB - Ninety-eight miRNAs are involved in the immune response. However, the genetic roles of these miRNAs remain unclear in Behcet's disease (BD) and Vogt-Koyanagi Harada (VKH) syndrome. This study aimed to explore the association and functional roles of copy number variants (CNV) in several miRNAs with BD and VKH syndrome. Genotyping of CNVs was examined by TaqMan PCR. The expression of miR-23a, transfection efficiency and cytokine production were measured by real-time PCR, flow cytometry or ELISA. First, replication and combined studies for miR-23a, miR 146a and miR-301a demonstrated a similar association with VKH syndrome (Combined: P = 5.53 * 10(-8); P = 8.43 * 10(-31); P = 9.23 * 10(-8), respectively). No association of CNVs of the above mentioned miRNAs was observed in BD patients. mRNA expression of miR-23a showed a positive association with its copy numbers. Additionally, individuals with high copy number of miR-23a show an increased production of interleukin-6 (IL-6), but not IL-8 and monocyte chemoattractant protein-1 (MCP-1) by stimulated PBMCs. miR-23a transfected ARPE-19 cells modulated the production of IL-6 and IL-8, but not MCP-1. Our results suggest that CNVs of miR-146a, miR-23a and miR-301a confer susceptibility to VKH syndrome, but not to BD. The contribution of miR-23a to VKH syndrome may be mediated by increasing the production of IL-6. PMID- 26818977 TI - Trends in malignant intraductal papillary mucinous neoplasm in US adults from 1990 to 2010: a SEER database analysis. AB - BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are precancerous lesions with a well-described adenoma-carcinoma sequence. Although the risk of malignant transformation has been well studied, data on trends in long-term survival and important prognostic factors associated with survival in malignant IPMN are lacking. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with confirmed malignant IPMN based upon pathologic diagnosis or radiographic evidence concerning for malignant potential. Median survival and age-adjusted incidence were calculated. Cox proportional hazard regression was used to determine independent mortality factors. RESULTS: Based upon the SEER database query, 2651 patients were diagnosed with malignant IPMN between 1990 and 2010. The age-adjusted incidence of IPMN in 1990 was 0.361 per 100 000 persons (95% confidence interval [CI]: 0.285-0.451) with a steady decline observed through 2010 (0.135 per 100 000 persons, 95% CI: 0.098-0.186). A total of 564 patients (21.3%) underwent a surgical procedure, though the number of patients who underwent surgery from 1990 to 2010 also decreased (1990-1995, n = 132 to 2006-2010, n = 96, respectively). The overall median survival was 4 months and remained relatively stable from 1990 to 2010. Performance of surgery (HR: 0.45, 95% CI: 0.40-0.53, P < 0.001) was associated with a decreased risk of death. CONCLUSION: A significant decrease in the incidence of malignant IPMN was seen from 1990 to 2010. There was also no improvement observed in long-term survival. The small percentage of eligible cases receiving surgical treatment suggests that there is room for further improvement in survival, with increased utilization of surgery. PMID- 26818979 TI - Prevalence of Nontyphoidal Salmonella and Salmonella Strains with Conjugative Antimicrobial-Resistant Serovars Contaminating Animal Feed in Texas. AB - The objective of this study was to characterize 365 nontyphoidal Salmonella enterica isolates from animal feed. Among the 365 isolates, 78 serovars were identified. Twenty-four isolates (7.0%) were recovered from three of six medicated feed types. Three of these isolates derived from the medicated feed, Salmonella Newport, Salmonella Typhimurium var. O 5- (Copenhagen), and Salmonella Lexington var. 15+ (Manila), displayed antimicrobial resistance. Susceptibility testing revealed that only 3.0% (12) of the 365 isolates displayed resistance to any of the antimicrobial agents. These 12 isolates were recovered from unmedicated dry beef feed (n = 3), medicated dry beef feed (n = 3), cabbage culls (n = 2), animal protein products (n = 2), dry dairy cattle feed (n = 1), and fish meal (n = 1). Only Salmonella Newport and Salmonella Typhimurium var. O 5- (Copenhagen) were multidrug resistant. Both isolates possessed the IncA/C replicon and the blaCMY-2 gene associated with cephalosporin resistance. Plasmid replicons were amplified from 4 of 12 resistant isolates. Plasmids (40 kb) were Salmonella Montevideo and Salmonella Kentucky. Conjugation experiments were done using 7 of the 12 resistant isolates as donors. Only Salmonella Montevideo, possessing a plasmid and amplifying IncN, produced transconjugants. Transconjugants displayed the same antimicrobial resistance profile as did the donor isolate. Three isolates that amplified replicons corresponding to IncA/C or IncHI2 did not produce transconjugants at 30 or 37 degrees C. The results of this study suggest that the prevalence of antimicrobial-resistant Salmonella contaminating animal feed is low in Texas. However, Salmonella was more prevalent in feed by-products; fish meal had the highest prevalence (84%) followed by animal protein products (48%). Ten of the 35 feed types had no Salmonella contamination. Further investigation is needed to understand the possible role of specific feed types in the dissemination of antimicrobial resistant bacteria. PMID- 26818978 TI - Modeling the Impact of Ingoing Sodium Nitrite, Sodium Ascorbate, and Residual Nitrite Concentrations on Growth Parameters of Listeria monocytogenes in Cooked, Cured Pork Sausage. AB - Sodium nitrite has been identified as a key antimicrobial ingredient to control pathogens in ready-to-eat (RTE) meat and poultry products, including Listeria monocytogenes. This study was designed to more clearly elucidate the relationship between chemical factors (ingoing nitrite, ascorbate, and residual nitrite) and L. monocytogenes growth in RTE meats. Treatments of cooked, cured pork sausage (65% moisture, 1.8% salt, pH 6.6, and water activity 0.98) were based on response surface methodology with ingoing nitrite and ascorbate concentrations as the two main factors. Concentrations of nitrite and ascorbate, including star points, ranged from 0 to 352 and 0 to 643 ppm, respectively. At one of two time points after manufacturing (days 0 and 28), half of each treatment was surface inoculated to target 3 log CFU/g of a five-strain L. monocytogenes cocktail, vacuum packaged, and stored at 7 degrees C for up to 4 weeks. Growth of L. monocytogenes was measured twice per week, and enumerations were used to estimate lag time and growth rates for each treatment. Residual nitrite concentrations were measured on days 0, 4, 7, 14, 21, and 28, and nitrite depletion rate was estimated by using first-order kinetics. The response surface methodology was used to model L. monocytogenes lag time and growth rate based on ingoing nitrite, ascorbate, and the residual nitrite remaining at the point of inoculation. Modeling results showed that lag time was impacted by residual nitrite concentration remaining at inoculation, as well as the squared term of ingoing nitrite, whereas growth rate was affected by ingoing nitrite concentration but not by the remaining residual nitrite at the point of inoculation. Residual nitrite depletion rate was dependent upon ingoing nitrite concentration and was only slightly affected by ascorbate concentration. This study confirmed that ingoing nitrite concentration influences L. monocytogenes growth in RTE products, yet residual nitrite concentration contributes to the antimicrobial impact of nitrite as well. PMID- 26818980 TI - Inactivation of Escherichia coli O157:H7 in Beef Roasts Cooked in Conventional or Convection Ovens or in a Slow Cooker under Selected Conditions. AB - Inactivation of Escherichia coli O157:H7 in beef roasts cooked under selected cooking conditions was evaluated. Eye of round roasts were each inoculated at five sites in the central plane with a five-strain cocktail of E. coli O157:H7 at ca. 6.3 log CFU per site and cooked to center temperatures of 56 to 71 degrees C in a convection oven set at 120, 140, 180, or 200 degrees C, in a conventional oven set at 120 or 210 degrees C, and in a slow cooker set on high or low. Prime rib roasts were each inoculated at 10 sites throughout the roast with the same E. coli O157:H7 cocktail at ca. 6.6 log CFU per site and cooked in the conventional oven set at 140 or 180 degrees C to center temperatures of 58 to 71 degrees C. The number of sites yielding E. coli O157:H7 after cooking decreased with increasing roast center temperature for the eye of round roasts cooked in the convection oven or in the slow cooker at a given setting, but this trend was not apparent for roasts of either type cooked in the conventional oven. Reductions of E. coli O157 in both types of roasts were generally less at the center than at other locations, particularly locations closer to the surface of the meat. When eye of round roasts were cooked to the same center temperature in the convection oven, the reduction of E. coli O157:H7 increased with increasing oven temperature up to 180 degrees C and decreased after that. The reduction of E. coli O157:H7 in replicate roasts cooked under conditions in which the organism was not eliminated during cooking mostly differed by >1 log CFU per site. However, E. coli O157:H7 was not recovered from any of the inoculation sites when eye of round roasts were cooked to 65, 60, 60, or 63 degrees C in the convection oven set at 120, 140, 180, and 200 degrees C, respectively; cooked to 63 or 71 degrees C in the conventional oven set at 120 and 210 degrees C, respectively; or cooked to 63 degrees C in the slow cooker set at high or low. For prime rib roasts, E. coli O157:H7 was not recovered from any of the inoculation sites in roasts cooked to 71 or 58 degrees C in the conventional oven set at 140 and 180 degrees C, respectively. PMID- 26818981 TI - Inactivation of Escherichia coli, Listeria monocytogenes, and Salmonella Enteritidis by Cymbopogon citratus D.C. Stapf. Essential Oil in Pineapple Juice. AB - In the present study, the efficacy of Cymbopogon citratus D.C. Stapf. essential oil (CCEO) to provoke a 5-log CFU/ml (5-log) inactivation in a mixed composite of Escherichia coli, Listeria monocytogenes, and Salmonella enterica serovar Enteritidis in pineapple (Ananas comosus (L.) Merril) juice (4 degrees C) was assessed. Moreover, the effects of CCEO on the physicochemical and sensory quality parameters of pineapple juice were evaluated. The MIC of CCEO was 5 MUl/ml against the composite mix examined. For L. monocytogenes and E. coli inoculated in juice containing CCEO (5, 2.5, and 1.25 MUl/ml), a >=5-log reduction was detected after 15 min of exposure. This same result was obtained for Salmonella Enteritidis incubated alone in pineapple juice containing CCEO at 5 and 2.5 MUl/ml. Overall, Salmonella Enteritidis was the most tolerant and L. monocytogenes was the most sensitive to CCEO. The physicochemical properties (pH, titratable acidic [citric acid per 100 g], and soluble solids) of pineapple juice containing CCEO (2.5 and 1.25 MUl/ml) were maintained. Juice containing CCEO (2.5 and 1.25 MUl/ml) exhibited similar scores for odor, appearance, and viscosity compared with juice without CCEO. However, unsatisfactory changes in taste and aftertaste were observed in juices containing CCEO. These results suggest that CCEO could be used as an alternative antimicrobial compound to ensure the safety of pineapple juice, although CCEO at the tested concentrations negatively impacted its taste. Therefore, further studies are needed to determine the balance between microbial safety and taste acceptability of pineapple juice containing CCEO. PMID- 26818983 TI - Characterization and Exposure Assessment of Emetic Bacillus cereus and Cereulide Production in Food Products on the Dutch Market. AB - The emetic toxin cereulide, which can be produced by Bacillus cereus, can be the cause of food poisoning upon ingestion by the consumer. The toxin causes vomiting and is mainly produced in farinaceous food products. This article includes the prevalence of B. cereus and of cereulide in food products in The Netherlands, a characterization of B. cereus isolates obtained, cereulide production conditions, and a comparison of consumer exposure estimates with those of a previous exposure assessment. Food samples (n = 1,489) were tested for the presence of B. cereus; 5.4% of the samples contained detectable levels (>10(2) CFU/g), and 0.7% contained levels above 10(5) CFU/g. Samples (n = 3,008) also were tested for the presence of cereulide. Two samples (0.067%) contained detectable levels of cereulide at 3.2 and 5.4 MUg/kg of food product. Of the 481 tested isolates, 81 produced cereulide and/or contained the ces gene. None of the starch-positive and hbl-containing isolates possessed the ces gene, whereas all strains contained the nhe genes. Culture of emetic B. cereus under nonoptimal conditions revealed a delay in onset of cereulide production compared with culture under optimal conditions, and cereulide was produced in all cases when B. cereus cells had been in the stationary phase for some time. The prevalence of cereulide-contaminated food approached the prevalence of contaminated products estimated in an exposure assessment. The main food safety focus associated with this pathogen should be to prevent germination and growth of any B. cereus present in food products and thus prevent cereulide production in foods. PMID- 26818982 TI - Exploring the Bacterial Diversity of Belgian Steak Tartare Using Metagenetics and Quantitative Real-Time PCR Analysis. AB - Steak tartare is a popular meat dish in Belgium. It is prepared with raw minced beef and is eaten with sauce, vegetables, and spices. Because it contains raw meat, steak tartare is highly prone to bacterial spoilage. The objective of this study was to explore the diversity of bacterial flora in steak tartare in Belgium according to the source and to determine which bacteria are able to grow during shelf life. A total of 58 samples from butchers' shops, restaurants, sandwich shops, and supermarkets were collected. These samples were analyzed using 16S rDNA metagenetics, a classical microbiological technique, and quantitative real time PCR (qPCR) targeting the Lactobacillus genus. Samples were analyzed at the beginning and at the end of their shelf life, except for those from restaurants and sandwich shops, which were analyzed only on the purchase date. Metagenetic analysis identified up to 180 bacterial species and 90 genera in some samples. But only seven bacterial species were predominant in the samples, depending on the source: Brochothrix thermosphacta, Lactobacillus algidus, Lactococcus piscium, Leuconostoc gelidum, Photobacterium kishitani, Pseudomonas spp., and Xanthomonas oryzae. With this work, an alternative method is proposed to evaluate the total flora in food samples based on the number of reads from metagenetic analysis and the results of qPCR. The degree of underestimation of aerobic plate counts at 30 degrees C estimated with the classical microbiology method was demonstrated in comparison with the proposed culture-independent method. Compared with culture-based methods, metagenetic analysis combined with qPCR targeting Lactobacillus provides valuable information for characterizing the bacterial flora of raw meat. PMID- 26818984 TI - Various Ready-to-Eat Products from Retail Stores Linked to Occurrence of Diverse Listeria monocytogenes and Listeria spp. Isolates. AB - Listeriosis outbreaks have been associated with a variety of foods. This study investigated the prevalence and diversity of Listeria monocytogenes and Listeria spp. in ready-to-eat (RTE) products and evaluated the performance of a rapid detection method, the 3M molecular detection assay for L. monocytogenes (MDA-LM), for detection of L. monocytogenes. Assay results were compared with those obtained using the U.S. Food and Drug Administration standard culture method described in the Bacteriological Analytical Manual. Products (n = 200) were purchased from retail stores: 122 aquatic products, 22 products of animal origin, 18 vegetarian products, 15 deli meat products, 13 salad and vegetable products, 4 desserts, 2 egg-based products, and 4 other products. L. monocytogenes prevalence was comparable with both methods. Overall, 15 (7.5%) of 200 samples were positive for L. monocytogenes: 3% of aquatic products, 1.5% of products of animal origin, 1% of vegetarian products, and 2% of deli meat products. Compared with the standard culture method, the sensitivity, specificity, and the accuracy of the MDA-LM were 86.7% (95% confidence interval, 58.4 to 97.7%), 98.4% (95% confidence interval, 95.0 to 99.6%), and 97.5%, respectively. Using the culture-based method, 18 (9%) of 200 samples were positive for Listeria species other than L. monocytogenes. Listeria isolates from these samples were classified into nine allelic types (ATs). The majority of isolates were classified as ATs 58 and 74, which were identified as L. monocytogenes lineages I and IV, respectively. Listeria innocua and Listeria welshimeri also were represented by isolates of multiple ATs. The MDA-LM is a rapid and reliable technique for detecting L. monocytogenes in various RTE foods. Further study is needed to develop effective control strategies to reduce L. monocytogenes contamination in RTE foods. PMID- 26818985 TI - Effects of the Essential Oil from Origanum vulgare L. on Survival of Pathogenic Bacteria and Starter Lactic Acid Bacteria in Semihard Cheese Broth and Slurry. AB - This study assessed the inhibitory effects of the essential oil from Origanum vulgare L. (OVEO) on Staphylococcus aureus, Listeria monocytogenes, and a mesophilic starter coculture composed of lactic acid bacteria (Lactococcus lactis subsp. lactis and L. lactis subsp. cremoris) in Brazilian coalho cheese systems. The MIC of OVEO was 2.5 MUl/ml against both S. aureus and L. monocytogenes and 0.6 MUl/ml against the tested starter coculture. In cheese broth containing OVEO at 0.6 MUl/ml, no decrease in viable cell counts (VCC) of both pathogenic bacteria was observed, whereas the initial VCC of the starter coculture decreased approximately 1.0 log CFU/ml after 24 h of exposure at 10 degrees C. OVEO at 1.25 and 2.5 MUl/ml caused reductions of up to 2.0 and 2.5 log CFU/ml in S. aureus and L. monocytogenes, respectively, after 24 h of exposure in cheese broth. At these same concentrations, OVEO caused a greater decrease of initial VCC of the starter coculture following 4 h of exposure. Higher concentrations of OVEO were required to decrease the VCC of all target bacteria in semisolid coalho cheese slurry compared with cheese broth. The VCC of Lactococcus spp. in coalho cheese slurry containing OVEO were always lower than those of pathogenic bacteria under the same conditions. These results suggest that the concentrations of OVEO used to control pathogenic bacteria in semihard cheese should be carefully evaluated because of its inhibitory effects on the growth of starter lactic acid cultures used during the production of the product. PMID- 26818986 TI - Thermal and Pressure-Assisted Thermal Destruction Kinetics for Spores of Type A Clostridium botulinum and Clostridium sporogenes PA3679. AB - The purpose of this study was to determine the inactivation kinetics of the spores of the most resistant proteolytic Clostridium botulinum strains (Giorgio-A and 69-A, as determined from an earlier screening study) and of Clostridium sporogenes PA3679 and to compare the thermal and pressure-assisted thermal resistance of these spores. Spores of these strains were prepared using a biphasic medium method. C. sporogenes PA3679 spores were heat treated before spore preparation. Using laboratory-scale and pilot-scale pressure test systems, spores of Giorgio-A, 69-A, and PA3679 suspended in ACES [N-(2-acetamido)-2 aminoethanesulfonic acid] buffer (pH 7.0) were exposed to various combinations of temperature (93 to 121 degrees C) and pressure (0.1 to 750 MPa) to determine their resistance. More than a 5-log reduction occurred after 3 min at 113 degrees C for spores of Giorgio-A and 69-A and after 5 min at 117 degrees C for spores of PA3679. A combination of high temperatures (93 to 121 degrees C) and pressures yielded greater log reductions of spores of Giorgio-A, 69-A, and PA3679 compared with reduction obtained with high temperatures alone. No survivors from initial levels (>5.0 log CFU) of Giorgio-A and 69-A were detected when processed at a combination of high temperature (117 and 121 degrees C) and high pressure (600 and 750 MPa) for <1 min in a pilot-scale pressure test system. Increasing pressure from 600 to 750 MPa at 117 degrees C decreased the time from 2.7 to 1 min for a >4.5-log reduction of PA3679 spores. Thermal D-values of Giorgio-A, 69 A, and PA3679 spores decreased (i.e., 29.1 to 0.33 min for Giorgio-A, 40.5 to 0.27 min for 69-A, and 335.2 to 2.16 min for PA3679) as the temperature increased from 97 to 117 degrees C. Pressure-assisted thermal D-values of Giorgio-A, 69-A, and PA3679 also decreased as temperature increased from 97 to 121 degrees C at both pressures (600 and 750 MPa) (i.e., 17.19 to 0.15 min for Giorgio-A, 9.58 to 0.15 min for 69-A, and 12.93 to 0.33 min for PA3679 at 600 MPa). At higher temperatures (117 or 121 degrees C), increasing pressure from 600 to 750 MPa had an effect on pressure-assisted thermal D-values of PA3679 (i.e., at 117 degrees C, pressure-assisted thermal D-value decreased from 0.55 to 0.28 min as pressure increased from 600 to 750 MPa), but pressure had no effect on pressure-assisted thermal D-values of Giorgio-A and 69-A. When compared with Giorgio-A and 69-A, PA3679 had higher thermal and pressure-assisted thermal D-values. C. sporogenes PA3679 spores were generally more resistant to combinations of high pressure and high temperature than were the spores of the C. botulinum strains tested in this study. PMID- 26818987 TI - Older Adult Consumer Knowledge, Attitudes, and Self-Reported Storage Practices of Ready-to-Eat Food Products and Risks Associated with Listeriosis. AB - Consumer implementation of recommended food safety practices, specifically relating to time and temperature control of ready-to-eat (RTE) food products associated with listeriosis are crucial. This is particularly the case for at risk consumers such as older adults, given the increased listeriosis incidence reported internationally among adults aged >=60 years. However, data detailing older adults' cognitive risk factors associated with listeriosis are lacking. Combining data about knowledge, self-reported practices, and attitudes can achieve a cumulative multilayered in-depth understanding of consumer food safety behavior and cognition. This study aims to ascertain older adults' cognition and behavior in relation to domestic food handling and storage practices that may increase the risks associated with L. monocytogenes. Older adults (>=60 years) (n = 100) participated in an interview and questionnaire to determine knowledge, self-reported practices, and attitudes toward recommended practices. Although the majority (79%) had positive attitudes toward refrigeration, 84% were unaware of recommended temperatures (5 degrees C) and 65% self-reported "never" checking their refrigerator temperature. Although most (72%) knew that "use-by" dates indicate food safety and 62% reported "always" taking note, neutral attitudes were held, with 67% believing it was safe to eat food beyond use-by dates and 57% reporting doing so. Attitudes toward consuming foods within the recommended 2 days of opening were neutral, with 55% aware of recommendations and , 84% reporting that they consume RTE foods beyond recommendations. Although knowledgeable of some key practices, older adults self-reported potentially unsafe practices when storing RTE foods at home, which may increase risks associated with L. monocytogenes. This study has determined that older adults' food safety cognition may affect their behaviors; understanding consumer food safety cognition is essential for developing targeted food safety education. PMID- 26818988 TI - High-Throughput Quantification of Monofluoroacetate (1080) in Milk as a Response to an Extortion Threat. AB - As a food defense measure against an extortion threat to poison infant formula with monofluoroacetate, a robust methodology for monofluoroacetate analysis in fluid milk and powdered dairy products was developed and optimized. Critical challenges posed by this situation required that the analytical methodology provide (i) high specificity, (ii) high throughput capable of analyzing thousands of samples of fluid milk per day, and (iii) trace-level detection of 1 ng/g or lower to achieve the maximum residue limit. Solid-phase extraction-purified acetone extracts of fluid milk were derivatized with aniline, and after ultrahigh performance liquid chromatography using a Kinetex-C18 column packed with 1.3-MUm shell particles, the resulting N-phenyl 2-fluoroacetamide could be determined by liquid chromatography-tandem mass spectrometry in a highly specific manner and with a limit of quantification of 0.5 ng/ml. By using 4-(4-chlorophenoxy)aniline as a derivatizing agent, the method could be extended to powdered dairy products with the same limit of quantification. Between January and July 2015, some 136,000 fluid milk samples were tested using this method. This analytical testing of fluid milk formed one element in a larger program of work by multiple agencies to ensure that consumers could continue to have confidence in the safety of New Zealand milk and dairy products. PMID- 26818989 TI - Catering Gluten-Free When Simultaneously Using Wheat Flour. AB - A European law on gluten-free (GF) labeling came into force in 2012, covering foods sold prepacked and in food service establishments, and a similar U.S. Food and Drug Administration (FDA) regulation covers GF labeling from August 2014. Gluten is found in the grains wheat, rye, and barley. A common source of gluten in the kitchen is wheat flour. This research aimed to determine variables that have a significant effect on gluten contamination in commercial kitchens when wheat flour is in use and to establish controls necessary to assure GF production. A pilot study was used to test the following hypotheses: (i) increasing duration of exposure to wheat flour would increase gluten contamination, (ii) increasing distance between the site of preparation and the site of wheat flour would reduce gluten contamination, (iii) the use of a ventilation hood would decrease gluten contamination, and (iv) the use of a barrier segregating the site of preparation of a GF meal and the use of wheat flour would decrease gluten contamination. Petri dishes containing GF rice pudding were placed in three directions at increasing distances (0.5 to 2 m) from a site of wheat flour use. A barrier was in place between a third of samples and the site of wheat flour. After wheat flour was handled for 0.5 and 4.0 h, petri dishes were sealed and the contents were analyzed for gluten. The experiment was duplicated with the ventilation hood on and off. The pilot study revealed that a distance of 2 m from the use of wheat flour was required to control gluten contamination at <=20 ppm if wheat flour had been in use for 4.0 h. The identified control of distance was tested in five different study sites. In each of the study sites, a test meal was prepared a minimum of 2 m away from the site of wheat flour use. Although kitchens vary and must be considered individually, the established control of a minimum 2 m distance, along with good hygiene practices, was found to be effective in preparing GF meals at all five study sites. PMID- 26818990 TI - Pathogenicity of Vibrio parahaemolyticus in Different Food Matrices. AB - The pathogenicity and virulence factors of Vibrio parahaemolyticus in four food matrices--shrimp, freshwater fish, pork, and egg-fried rice--were compared by measuring the thermostable direct hemolysin activity and total hemolytic titer. Significantly high thermostable direct hemolysin and also hemolytic titers (P < 0.05) were produced by V. parahaemolyticus in egg-fried rice > shrimp > freshwater fish > pork. Filtrates of V. parahaemolyticus in shrimp given intraperitoneally induced marked liver and kidney damage and were highly lethal to adult mice compared with filtrates of V. parahaemolyticus in freshwater fish > egg-fried rice > pork. From in vitro and in vivo pathogenicity tests, it seems the type of food matrix has a significant impact on the virulence of V. parahaemolyticus. These results suggest that hemolysin may not necessarily be the only virulence factor for pathogenicity of V. parahaemolyticus. This is the first report that shows that virulence factors produced by V. parahaemolyticus in seafood such as shrimp are more toxic in vivo than in nonseafood. PMID- 26818991 TI - UV Tolerance of Spoilage Microorganisms and Acid-Shocked and Acid-Adapted Escherichia coli in Apple Juice Treated with a Commercial UV Juice-Processing Unit. AB - The enhanced thermal tolerance and survival responses of Escherichia coli O157:H7 in acid and acidified foods is a major safety concern for the production of low pH products, including beverages. Little is known about this phenomenon when using UV light treatments. This study was conducted to evaluate the effects of strain (E. coli O157:H7 strains C7927, ATCC 35150, ATCC 43895, and ATCC 43889 and E. coli ATCC 25922) and physiological state (control-unadapted, acid adapted, and acid shocked) on the UV tolerance of E. coli in apple juice treated under conditions stipulated in current U.S. Food and Drug Administration regulations. A greater than 5-log reduction of E. coli was obtained under all tested conditions. A significant effect of strain (P < 0.05) was observed, but the physiological state did not influence pathogen inactivation (P >= 0.05). The UV sensitivity of three spoilage microorganisms (Aspergillus niger, Penicillium commune, and Alicyclobacillus acidoterrestris) was also determined at UV doses of 0 to 98 mJ/cm(2). Alicyclobacillus was the most UV sensitive, followed by Penicillium and Aspergillus. Because of the nonsignificant differences in UV sensitivity of E. coli in different physiological states, the use of an unadapted inoculum would be adequate to conduct challenge studies with the commercial UV unit used in this study at a UV dose of 14 mJ/cm(2). The high UV tolerance of spoilage microorganisms supports the need to use a hurdle approach (e.g., coupling of refrigeration, preservatives, and/or other technologies) to extend the shelf life of UV-treated beverages. PMID- 26818992 TI - In Vitro Effects of Thymol-beta-D-Glucopyranoside on Salmonella enterica Serovar Typhimurium and Escherichia coli K88. AB - Although thymol is bactericidal against many pathogens in vitro, its in vivo effectiveness against pathogens in the lower gastrointestinal tract is limited because of its rapid absorption in the proximal gut. Thymol-beta-D glucopyranoside (beta-thymol), a conjugated form of thymol, can deliver thymol to the lower gastrointestinal tract and has shown antibacterial effects. In the present study, we examined the in vitro effects of beta-thymol on Salmonella enterica serovar Typhimurium (ST) and Escherichia coli K88 (K88). We inoculated one-half strength Mueller-Hinton broth with 5.8 +/- 0.09 log CFU/ml novobiocin- and naladixic acid-resistant (NN) ST (NVSL 95-1776) and 5.1 +/- 0.09 log CFU ml( 1) NN-resistant K88, with or without porcine feces (0.1% [wt/vol]) (fecal incubations). The resultant bacterial suspensions were distributed under N2 to triplicate sets of tubes to achieve initial concentrations of 0, 3, 6, and 12 mM for ST treatments and 0, 3, 12, and 30 mM for K88 treatments. Samples were incubated at 39 degrees C and then plated onto NN-containing brilliant green agar and NN-containing MacConkey agar; ST and K88 CFU concentrations were determined via 10-fold dilutions, and viable cell counts were performed at 0, 6, and 24 h. No differences in ST CFU counts were observed in beta-thymol-treated tubes without the added porcine feces (i.e., pure culture) at 6 or 24 h. However, in tubes that contained fecal incubations, ST CFU counts were reduced (P < 0.05) from controls at 6 h in tubes treated with 6 and 12 mM beta-thymol, whereas in tubes treated with 3, 6, and 12 mM beta-thymol the CFU counts were reduced (P < 0.05) at 24 h. No differences were observed in K88 CFU counts in pure culture or in fecal incubations at 6 h, but K88 CFU counts were reduced (P < 0.05) in both pure and fecal incubations at 24 h. The results from this study demonstrate that beta-thymol, in the presence of fecal suspensions, has anti-Salmonella and anti E. coli effects, suggesting a role of beta-glycoside-hydrolyzing microbes for the release of bactericidal thymol from beta-thymol. PMID- 26818993 TI - Adequate Hand Washing and Glove Use Are Necessary To Reduce Cross-Contamination from Hands with High Bacterial Loads. AB - Hand washing and glove use are the main methods for reducing bacterial cross contamination from hands to ready-to-eat food in a food service setting. However, bacterial transfer from hands to gloves is poorly understood, as is the effect of different durations of soap rubbing on bacterial reduction. To assess bacterial transfer from hands to gloves and to compare bacterial transfer rates to food after different soap washing times and glove use, participants' hands were artificially contaminated with Enterobacter aerogenes B199A at ~9 log CFU. Different soap rubbing times (0, 3, and 20 s), glove use, and tomato dicing activities followed. The bacterial counts in diced tomatoes and on participants' hands and gloves were then analyzed. Different soap rubbing times did not significantly change the amount of bacteria recovered from participants' hands. Dicing tomatoes with bare hands after 20 s of soap rubbing transferred significantly less bacteria (P < 0.01) to tomatoes than did dicing with bare hands after 0 s of soap rubbing. Wearing gloves while dicing greatly reduced the incidence of contaminated tomato samples compared with dicing with bare hands. Increasing soap washing time decreased the incidence of bacteria recovered from outside glove surfaces (P < 0.05). These results highlight that both glove use and adequate hand washing are necessary to reduce bacterial cross-contamination in food service environments. PMID- 26818994 TI - Antimicrobial Activity of Individual and Combined Essential Oils against Foodborne Pathogenic Bacteria. AB - The antimicrobial activities of essential oils from Mexican oregano (Lippia berlandieri Schauer), mustard (Brassica nigra), and thyme (Thymus vulgaris) were evaluated alone and in binary combinations against Listeria monocytogenes, Staphylococcus aureus, or Salmonella Enteritidis. Chemical compositions of the essential oils were analyzed by gas chromatography-mass spectrometry. The MICs of the evaluated essential oils ranged from 0.05 to 0.50% (vol/vol). Mustard essential oil was the most effective, likely due to the presence of allyl isothiocyanate, identified as its major component. Furthermore, mustard essential oil exhibited synergistic effects when combined with either Mexican oregano or thyme essential oils (fractional inhibitory concentration indices of 0.75); an additive effect was obtained by combining thyme and Mexican oregano essential oils (fractional inhibitory concentration index = 1.00). These results suggest the potential of studied essential oil mixtures to inhibit microbial growth and preserve foods; however, their effect on sensory quality in selected foods compatible with their flavor needs to be assessed. PMID- 26818995 TI - Quality Control of Trichinella Testing at the Slaughterhouse Laboratory: Evaluation of the Use of a 400-Micrometer-Mesh-Size Sieve in the Magnetic Stirrer Method. AB - The performance of a 400-MUm-mesh-size sieve (sieve400) has not previously been compared with that of a 180-MUm-mesh-size sieve (sieve180). Using pork samples spiked with 0 to 10 Trichinella muscle larvae and an artificial digestion method, sieve performance was evaluated for control of Trichinella in meat-producing animals. The use of a sieve400 resulted in 12% lower larval counts, 147% more debris, and 28% longer counting times compared with the use of a sieve180. Although no false-negative results were obtained, prolonged counting times with the sieve400 may have an impact on performance in a high-throughput environment such as a slaughterhouse laboratory. Based on our results, the sieve180 remains the sieve of choice for Trichinella control in meat in slaughterhouse laboratories, according to the European Union reference method (European Commission regulation 2075/2005). Furthermore, the results of the present study contribute to the discussion of harmonization of meat inspection requirements among countries. PMID- 26818997 TI - Fresh Produce-Associated Listeriosis Outbreaks, Sources of Concern, Teachable Moments, and Insights. AB - Foodborne transmission of Listeria monocytogenes was first demonstrated through the investigation of the 1981 Maritime Provinces outbreak involving coleslaw. In the following two decades, most listeriosis outbreaks involved foods of animal origin, e.g., deli meats, hot dogs, and soft cheeses. L. monocytogenes serotype 4b, especially epidemic clones I, II, and Ia, were frequently implicated in these outbreaks. However, since 2008 several outbreaks have been linked to diverse types of fresh produce: sprouts, celery, cantaloupe, stone fruit, and apples. The 2011 cantaloupe-associated outbreak was one of the deadliest foodborne outbreaks in recent U.S. history. This review discusses produce-related outbreaks of listeriosis with a focus on special trends, unusual findings, and potential paradigm shifts. With the exception of sprouts, implicated produce types were novel, and outbreaks were one-time events. Several involved serotype 1/2a, and in the 2011 cantaloupe-associated outbreak, serotype 1/2b was for the first time conclusively linked to a common-source outbreak of invasive listeriosis. Also in this outbreak, for the first time multiple strains were implicated in a common source outbreak. In 2014, deployment of whole genome sequencing as part of outbreak investigation validated this technique as a pivotal tool for outbreak detection and speedy resolution. In spite of the unusual attributes of produce related outbreaks, in all but one of the investigated cases (the possible exception being the coleslaw outbreak) contamination was traced to the same sources as those for outbreaks associated with other vehicles (e.g., deli meats), i.e., the processing environment and equipment. The public health impact of farm level contamination remains uncharacterized. This review highlights knowledge gaps regarding virulence and other potentially unique attributes of produce outbreak strains, the potential for novel fresh produce items to become unexpectedly implicated in outbreaks, and the key role of good control strategies in the processing environment. PMID- 26818996 TI - Combating Antimicrobial Resistance in Foodborne Microorganisms. AB - This review addresses an important public health hazard affecting food safety. Antimicrobial agents are used in foods to reduce or eliminate microorganisms that cause disease. Many traditional organic compounds, novel synthetic organic agents, natural products, peptides, and proteins have been extensively studied for their effectiveness as antimicrobial agents against foodborne Campylobacter spp., Escherichia coli, Listeria spp. and Salmonella. However, antimicrobial resistance can develop in microorganisms, enhancing their ability to withstand the inhibiting or killing action of antimicrobial agents. Knowledge gaps still exist with regard to the actual chemical and microbiological mechanisms that must be identified to facilitate the search for new antimicrobial agents. Technical implementation of antimicrobial active packing films and coatings against target microorganisms must also be improved for extended product shelf life. Recent advances in antimicrobial susceptibility testing can provide researchers with new momentum to pursue their quest for a resistance panacea. PMID- 26818998 TI - A case of probable macrogol allergy in urticaria/angioedema patient. PMID- 26818999 TI - Insight to the binding mode of triazole RGD-peptidomimetics to integrin-rich cancer cells by NMR and molecular modeling. AB - The binding features of a novel class of 'click chemistry'-derived RGD mimics with integrin ligand capability were studied toward alphavbeta3 integrin using STD-NMR techniques on intact integrin-rich ECV340 bladder cancer cell line. STD is useful to identify which moieties of the ligand are closest to the receptor in the bound state. The NMR data were integrated with competitive binding assays to the purified alphavbeta3 receptor and were interpreted with the aid of docking calculations. The involvement of the triazole hydrogen atom in the interaction with the receptor was evinced for all compounds but 2, in agreement with docking studies showing a certain proximity between triazole and Tyr178. Moreover, the interaction of the hydroxylated ligands with the receptor was not as extended as in the compounds belonging to the corresponding series, with the exception of compound 4 having 2-aminobenzimidazole as the arginine bioisostere, in agreement with biological assay results showing reduced binding capability for the hydroxylated peptidomimetics. PMID- 26819001 TI - Discovery of benzenesulfonamide derivatives as potent PI3K/mTOR dual inhibitors with in vivo efficacies against hepatocellular carcinoma. AB - The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is related to cellular activities. Abnormalities of this signaling pathway were discovered in various cancers, including hepatocellular carcinoma (HCC). The PI3K/mTOR dual inhibitors were proposed to have enhanced antitumor efficacies by targeting multiple points of the signaling pathway. We synthesized a series of propynyl-substituted benzenesulfonamide derivatives as PI3K/mTOR dual inhibitors. Compound 7k (NSC781406) was identified as a highly potent dual inhibitor, which exhibited potent tumor growth inhibition in the hepatocellular carcinoma BEL-7404 xenograft model. Compound 7k may be a potential therapeutic drug candidate for HCC. PMID- 26819000 TI - Discovery of novel phenoxazinone derivatives as DKK1/LRP6 interaction inhibitors: Synthesis, biological evaluation and structure-activity relationships. AB - Amino derivatives of NCI8642 were synthesized and evaluated as inhibitors of DKK1/LRP6 interactions. The new inhibitors were able to activate the Wnt signaling pathway as indicated by the increased levels of beta-catenin, and decrease the DKK1-induced Tau phosphorylation at serine 396. PMID- 26819002 TI - Axonal TDP-43 aggregates in sporadic amyotrophic lateral sclerosis. AB - AIMS: Axonal aggregates of phosphorylated (p-) transactive response DNA-binding protein 43 kDa (TDP-43) in sporadic amyotrophic lateral sclerosis (sALS) were examined in relation to propagation of the protein in the nervous system. METHODS: Brains and spinal cords of Japanese patients with sALS and control subjects were examined immunohistochemically using formalin-fixed paraffin embedded specimens with special reference to the topographical distribution, microscopic features, presynaptic aggregates, and correlation between the aggregates in axons and the clinical course. RESULTS: (i) Aggregates of p-TDP-43 were frequently present in axons of the hypoglossal and facial nerve fibres and the spinal anterior horn cells. (ii) Aggregates of p-TDP-43 in the axons showed two characteristic microscopic features - dash-like granuloreticular aggregates (GRAs) and massive aggregates (MAs). (iii) MAs were surrounded by p neurofilaments, but p-neurofilament immunnoreactivity decreased at the inside of axons with GRAs. (iv) Patients showing MAs and GRAs had a relatively shorter clinical course than patients without the aggregates. (v) Some neurones in the red nucleus in patients were surrounded by synapses containing p- and p independent (i)-TDP-43, and almost all neurones had lost their nuclear TDP-43 immunoreactivity; 17% of those neurones in the red nucleus also had TDP-43 immunopositive neuronal cytoplasmic inclusions, but no postsynaptic p-TDP-43 deposition was evident. CONCLUSIONS: There are two types of axonal p-TDP-43 aggregates, MAs and GRAs, located predominantly in the facial and hypoglossal nuclei and anterior horn cells. These aggregates may influence the function of neurones, and presynaptic aggregates of the protein induce loss of p-i-TDP-43 in the nuclei of postsynaptic neurones. PMID- 26819003 TI - Low paediatric thrombin generation is caused by an attenuation of prothrombin conversion. AB - Thrombin generation (TG) is decreased in children. TG is determined by two underlying processes: the conversion of prothrombin to thrombin and the inactivation of thrombin. Therefore, lower TG capacity in children can either be caused by a reduction of prothrombin conversion, an increase of thrombin inactivation, or both. In 36 children and 8 adults, TG and the factors that determine thrombin inactivation (antithrombin, alpha2Macroglobulin (alpha2M) and fibrinogen) were measured. Prothrombin conversion, thrombin inhibitor complex formation, and the overall thrombin decay capacity were determined. In silico modelling was performed to determine the contribution prothrombin conversion and thrombin inactivation to deviant paediatric TG. Both the amount of prothrombin converted and the maximal prothrombin conversion rate are significantly reduced in children as compared to adults. This is partly due to the prothrombin levels being lower and partly to a lower prothrombin conversion rate. The overall thrombin decay capacity is not significantly different in children, but alpha2Macroglobulin plays a more important role than it does in adults. In silico experiments demonstrate that reduced prothrombin conversion and to a lesser extent elevated alpha2M levels provide an explanation for low TG in children. Young age has a dual effect on prothrombin conversion. Lower plasma prothrombin levels result in decreased prothrombin conversion but the rate of prothrombin conversion is also decreased, i. e. the development of prothrombinase is lower than in adults. PMID- 26819005 TI - Disconnected pancreatic duct syndrome: complete pancreas transection secondary to acute pancreatitis. AB - Disconnected pancreatic duct syndrome is a serious complication of acute pancreatitis which is defined by a complete discontinuity of the pancreatic duct, such that a viable side of the pancreas remains isolated from the gastrointestinal tract. This pancreatic disruption is infrequently observed in the clinical practice and its diagnostic and therapeutic management are controversial. We present an extreme case of disconnected pancreatic duct syndrome with complete duct disruption and pancreatic transection following acute pancreatitis, as well as the diagnostic and therapeutic processes carried out. PMID- 26819006 TI - Digital intuition. PMID- 26819007 TI - In praise of parks. PMID- 26819004 TI - Two di-leucine motifs regulate trafficking and function of mouse ASIC2a. AB - BACKGROUND: Acid-sensing ion channels (ASICs) are proton-gated cation channels that mediate acid-induced responses in neurons. ASICs are important for mechanosensation, learning and memory, fear, pain, and neuronal injury. ASIC2a is widely expressed in the nervous system and modulates ASIC channel trafficking and activity in both central and peripheral systems. Here, to better understand mechanisms regulating ASIC2a, we searched for potential protein motifs that regulate ASIC2a trafficking. RESULTS AND CONCLUSIONS: We identified a LLDLL sequence in the C-terminal juxtamembrane region of ASIC2a. Deleting or mutating the LLDLL sequence increased total expression and surface levels of ASIC2a in CHO cells. Mutating either of the two LL motifs had a similar effect. We further assessed ASIC2a localization in organotypic hippocampal slice neurons. The LL motif mutants exhibited increased dendritic trafficking and elevated targeting to dendritic spines. Consistent with an efficient trafficking, the LL motif mutants increased acid-activated current density. In addition, mutating the second LL motif increased pH sensitivity of the channel. These data identify the LL motifs as a negative regulator of ASIC2a trafficking and function, and suggest novel regulatory mechanisms in acid signaling. PMID- 26819008 TI - Found out. PMID- 26819009 TI - India needs home-grown GM food to stop starvation. PMID- 26819021 TI - Google AI algorithm masters ancient game of Go. PMID- 26819022 TI - Dog DNA probed for clues to human psychiatric ills. PMID- 26819023 TI - Hawking's latest black-hole paper splits physicists. PMID- 26819024 TI - Monkeys genetically modified to show autism symptoms. PMID- 26819025 TI - 2015 declared the hottest year on record. PMID- 26819026 TI - Paris climate deal hinges on better carbon accountancy. PMID- 26819027 TI - Slaughter of the song birds. PMID- 26819028 TI - How quality control could save your science. PMID- 26819029 TI - Research integrity: Don't let transparency damage science. PMID- 26819032 TI - Renewables: Solar energy needs focus. PMID- 26819033 TI - Climate adaptation: Hold atmosphere in trust for all. PMID- 26819034 TI - Funding: What stops women getting more grants? PMID- 26819035 TI - Environmental management: Synthesize evidence to steer decisions. PMID- 26819036 TI - Government: Concern grows for Turkey's academics. PMID- 26819037 TI - Genome editing: The domestication of Cas9. PMID- 26819038 TI - Neuroscience: Fluorescent boost for voltage sensors. PMID- 26819039 TI - Evolution: A lizard that generates heat. PMID- 26819040 TI - Stellar astrophysics: The mystery of globular clusters. PMID- 26819041 TI - Bioanalytical devices: Technological leap for sweat sensing. PMID- 26819042 TI - Mastering the game of Go with deep neural networks and tree search. AB - The game of Go has long been viewed as the most challenging of classic games for artificial intelligence owing to its enormous search space and the difficulty of evaluating board positions and moves. Here we introduce a new approach to computer Go that uses 'value networks' to evaluate board positions and 'policy networks' to select moves. These deep neural networks are trained by a novel combination of supervised learning from human expert games, and reinforcement learning from games of self-play. Without any lookahead search, the neural networks play Go at the level of state-of-the-art Monte Carlo tree search programs that simulate thousands of random games of self-play. We also introduce a new search algorithm that combines Monte Carlo simulation with value and policy networks. Using this search algorithm, our program AlphaGo achieved a 99.8% winning rate against other Go programs, and defeated the human European Go champion by 5 games to 0. This is the first time that a computer program has defeated a human professional player in the full-sized game of Go, a feat previously thought to be at least a decade away. PMID- 26819043 TI - Formation of new stellar populations from gas accreted by massive young star clusters. AB - Stars in clusters are thought to form in a single burst from a common progenitor cloud of molecular gas. However, massive, old 'globular' clusters--those with ages greater than ten billion years and masses several hundred thousand times that of the Sun--often harbour multiple stellar populations, indicating that more than one star-forming event occurred during their lifetimes. Colliding stellar winds from late-stage, asymptotic-giant-branch stars are often suggested to be triggers of second-generation star formation. For this to occur, the initial cluster masses need to be greater than a few million solar masses. Here we report observations of three massive relatively young star clusters (1-2 billion years old) in the Magellanic Clouds that show clear evidence of burst-like star formation that occurred a few hundred million years after their initial formation era. We show that such clusters could have accreted sufficient gas to form new stars if they had orbited in their host galaxies' gaseous disks throughout the period between their initial formation and the more recent bursts of star formation. This process may eventually give rise to the ubiquitous multiple stellar populations in globular clusters. PMID- 26819045 TI - No iron fertilization in the equatorial Pacific Ocean during the last ice age. AB - The equatorial Pacific Ocean is one of the major high-nutrient, low-chlorophyll regions in the global ocean. In such regions, the consumption of the available macro-nutrients such as nitrate and phosphate is thought to be limited in part by the low abundance of the critical micro-nutrient iron. Greater atmospheric dust deposition could have fertilized the equatorial Pacific with iron during the last ice age--the Last Glacial Period (LGP)--but the effect of increased ice-age dust fluxes on primary productivity in the equatorial Pacific remains uncertain. Here we present meridional transects of dust (derived from the (232)Th proxy), phytoplankton productivity (using opal, (231)Pa/(230)Th and excess Ba), and the degree of nitrate consumption (using foraminifera-bound delta(15)N) from six cores in the central equatorial Pacific for the Holocene (0-10,000 years ago) and the LGP (17,000-27,000 years ago). We find that, although dust deposition in the central equatorial Pacific was two to three times greater in the LGP than in the Holocene, productivity was the same or lower, and the degree of nitrate consumption was the same. These biogeochemical findings suggest that the relatively greater ice-age dust fluxes were not large enough to provide substantial iron fertilization to the central equatorial Pacific. This may have been because the absolute rate of dust deposition in the LGP (although greater than the Holocene rate) was very low. The lower productivity coupled with unchanged nitrate consumption suggests that the subsurface major nutrient concentrations were lower in the central equatorial Pacific during the LGP. As these nutrients are today dominantly sourced from the Subantarctic Zone of the Southern Ocean, we propose that the central equatorial Pacific data are consistent with more nutrient consumption in the Subantarctic Zone, possibly owing to iron fertilization as a result of higher absolute dust fluxes in this region. Thus, ice-age iron fertilization in the Subantarctic Zone would have ultimately worked to lower, not raise, equatorial Pacific productivity. PMID- 26819047 TI - Photodegradation of 4-tert-butylphenol in aqueous solution by UV-C, UV/H2O2 and UV/S2O8(2-) system. AB - The photolytic degradation of 4-tert-butylphenol (4-t-BP) in aqueous solution was investigated using three kinds of systems: UV-C directly photodegradation system, UV/H2O2 and UV/S2O8(2-) system. Under experimental conditions, the degradation rate of 4-t-BP was in the order: UV/S2O8(2-) > UV/H2O2 > UV-C. The reaction kinetics of UV/S2O8(2-) system were thoroughly investigated. The increase of S2O8(2-) concentration enhanced the 4-t-BP degradation rate, which was inhibited when the concentration of S2O8(2-) exceeded 4.0 mM. The highest efficacy in 4-t BP degradation was obtained at pH 6.5. The oxidation rate of 4-t-BP could be accelerated by increasing the reaction temperature and irradiation intensity. The highest rate constant (kobs = 8.4 * 10(-2) min(-1)) was acquired when the reaction temperature was 45 degrees C. The irradiation intensity was measured by irradiation distance, and the optimum irradiation distance was 10 cm. Moreover, the preliminary mechanism of 4-t-BP degradation was studied. The bond scission of the 4-t-BP molecule occurred by the oxidation of SO4(*-), which dimerized and formed two main primary products. Under the conditions of room temperature (25 degrees C +/- 1 degrees C) and low concentration of K2S2O8 (0.5 mM), 35.4% of total organic carbon (TOC) was removed after 8.5-h irradiation. The results showed that UV/S2O8(2-) system was effective for the degradation of 4-t-BP. PMID- 26819044 TI - Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis. AB - Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual's state of health. Sampling human sweat, which is rich in physiological information, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications. PMID- 26819048 TI - Frequency, distribution and clinical management of incidental findings and extramedullary plasmacytomas in whole body diffusion weighted magnetic resonance imaging in patients with multiple myeloma. PMID- 26819049 TI - Frequent CTLA4-CD28 gene fusion in diverse types of T-cell lymphoma. AB - CTLA4 and CD28 are co-regulatory receptors with opposite roles in T-cell signaling. By RNA sequencing, we identified a fusion between the two genes from partial gene duplication in a case of angioimmunoblastic T-cell lymphoma. The fusion gene, which codes for the extracellular domain of CTLA4 and the cytoplasmic region of CD28, is likely capable of transforming inhibitory signals into stimulatory signals for T-cell activation. Ectopic expression of the fusion transcript in Jurkat and H9 cells resulted in enhanced proliferation and AKT and ERK phosphorylation, indicating activation of downstream oncogenic pathways. To estimate the frequency of this gene fusion in mature T-cell lymphomas, we examined 115 T-cell lymphoma samples of diverse subtypes using reverse transcriptase polymerase chain reaction analysis and Sanger sequencing. We identified the fusion in 26 of 45 cases of angioimmunoblastic T-cell lymphomas (58%), nine of 39 peripheral T-cell lymphomas, not otherwise specified (23%), and nine of 31 extranodal NK/T cell lymphomas (29%). We further investigated the mutation status of 70 lymphoma-associated genes using ultra-deep targeted resequencing for 74 mature T-cell lymphoma samples. The mutational landscape we obtained suggests that T-cell lymphoma results from diverse combinations of multiple gene mutations. The CTLA4-CD28 gene fusion is likely a major contributor to the pathogenesis of T-cell lymphomas and represents a potential target for anti-CTLA4 cancer immunotherapy. PMID- 26819050 TI - Activity of the Janus kinase inhibitor ruxolitinib in chronic lymphocytic leukemia: results of a phase II trial. PMID- 26819051 TI - Structural modeling of JAK1 mutations in T-cell acute lymphoblastic leukemia reveals a second contact site between pseudokinase and kinase domains. PMID- 26819052 TI - Natural killer cell licensing after double cord blood transplantation is driven by the self-HLA class I molecules from the dominant cord blood. PMID- 26819053 TI - Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia. AB - Abroad array of conditions can lead to neurological symptoms in chronic lymphocytic leukemia patients and distinguishing between clinically significant involvement of the central nervous system by chronic lymphocytic leukemia and symptoms due to other etiologies can be challenging. Between January 1999 and November 2014, 172 (4%) of the 4174 patients with chronic lymphocytic leukemia followed at our center had a magnetic resonance imaging of the central nervous system and/or a lumbar puncture to evaluate neurological symptoms. After comprehensive evaluation, the etiology of neurological symptoms was: central nervous system chronic lymphocytic leukemia in 18 patients (10% evaluated by imaging and/or lumbar puncture, 0.4% overall cohort); central nervous system Richter Syndrome in 15 (9% evaluated, 0.3% overall); infection in 40 (23% evaluated, 1% overall); autoimmune/inflammatory conditions in 28 (16% evaluated, 0.7% overall); other cancer in 8 (5% evaluated, 0.2% overall); and another etiology in 63 (37% evaluated, 1.5% overall). Although the sensitivity of cerebrospinal fluid analysis to detect central nervous system disease was 89%, the specificity was only 42% due to the frequent presence of leukemic cells in the cerebrospinal fluid in other conditions. No parameter on cerebrospinal fluid analysis (e.g. total nucleated cells, total lymphocyte count, chronic lymphocytic leukemia cell percentage) were able to offer a reliable discrimination between patients whose neurological symptoms were due to clinically significant central nervous system involvement by chronic lymphocytic leukemia and another etiology. Median overall survival among patients with clinically significant central nervous system chronic lymphocytic leukemia and Richter syndrome was 12 and 11 months, respectively. In conclusion, clinically significant central nervous system involvement by chronic lymphocytic leukemia is a rare condition, and neurological symptoms in patients with chronic lymphocytic leukemia are due to other etiologies in approximately 80% of cases. Analysis of the cerebrospinal fluid has high sensitivity but limited specificity to distinguish clinically significant chronic lymphocytic leukemia involvement from other etiologies. PMID- 26819054 TI - Association of acute myeloid leukemia's most immature phenotype with risk groups and outcomes. AB - The precise phenotype and biology of acute myeloid leukemia stem cells remain controversial, in part because the "gold standard" immunodeficient mouse engraftment assay fails in a significant fraction of patients and identifies multiple cell-types in others. We sought to analyze the clinical utility of a novel assay for putative leukemia stem cells in a large prospective cohort. The leukemic clone's most primitive hematopoietic cellular phenotype was prospectively identified in 109 newly-diagnosed acute myeloid leukemia patients, and analyzed against clinical risk groups and outcomes. Most (80/109) patients harbored CD34(+)CD38(-) leukemia cells. The CD34(+)CD38(-) leukemia cells in 47 of the 80 patients displayed intermediate aldehyde dehydrogenase expression, while normal CD34(+)CD38(-) hematopoietic stem cells expressed high levels of aldehyde dehydrogenase. In the other 33/80 patients, the CD34(+)CD38(-) leukemia cells exhibited high aldehyde dehydrogenase activity, and most (28/33, 85%) harbored poor-risk cytogenetics or FMS-like tyrosine kinase 3 internal tandem translocations. No CD34(+) leukemia cells could be detected in 28/109 patients, including 14/21 patients with nucleophosmin-1 mutations and 6/7 acute promyelocytic leukemia patients. The patients with CD34(+)CD38(-) leukemia cells with high aldehyde dehydrogenase activity manifested a significantly lower complete remission rate, as well as poorer event-free and overall survivals. The leukemic clone's most immature phenotype was heterogeneous with respect to CD34, CD38, and ALDH expression, but correlated with acute myeloid leukemia risk groups and outcomes. The strong clinical correlations suggest that the most immature phenotype detectable in the leukemia might serve as a biomarker for "clinically relevant" leukemia stem cells. ClinicalTrials.gov: NCT01349972. PMID- 26819055 TI - Early Th1 immunity promotes immune tolerance and may impair graft-versus-leukemia effect after allogeneic hematopoietic cell transplantation. PMID- 26819056 TI - Clinical impact of small subclones harboring NOTCH1, SF3B1 or BIRC3 mutations in chronic lymphocytic leukemia. PMID- 26819057 TI - Pegylated interferon alpha-2a for essential thrombocythemia during pregnancy: outcome and safety. A case series. PMID- 26819059 TI - Blood disorders stepping into the limelight. PMID- 26819060 TI - Simultaneous production of l-lactic acid with high optical activity and a soil amendment with food waste that demonstrates plant growth promoting activity. AB - A unique method to produce highly optically-active l-lactic acid and soil amendments that promote plant growth from food waste was proposed. Three Bacillus strains Bacillus subtilis KBKU21, B. subtilis N3-9 and Bacillus coagulans T27, were used. Strain KBKU21 accumulated 36.9 g/L l-lactic acid with 95.7% optical activity and 98.2% l-lactic acid selectivity when fermented at 43 degrees C for 84 h in a model kitchen refuse (MKR) medium. Residual precipitate fraction (anaerobically-fermented MKR (AFM) compost) analysis revealed 4.60%, 0.70% and 0.75% of nitrogen (as N), phosphorous (as P2O5), and potassium (as K2O), respectively. Additionally, the carbon to nitrogen ratio decreased from 13.3 to 10.6. AFM compost with KBKU21 promoted plant growth parameters, including leaf length, plant height and fresh weight of Brassica rapa (Komatsuna), than that by chemical fertilizers or commercial compost. The concept provides an incentive for the complete recycling of food waste, contributing towards a sustainable production system. PMID- 26819061 TI - [Alopecia areata secondary to the use of leflunomide in patients with rheumatoid arthritis: a case report and literature review]. AB - Rheumatoid arthritis is a chronic, highly disabling autoimmune disease that requires aggressive pharmacological treatment using immunomodulatory drugs grouped under the name of Disease-Modifying Anti-rheumatic Drugs (DMARDs). Leflunomide is one of the most frequently prescribed. This drug, through its mechanism of action is able to suppress key factors in the disease process. However, its use is not without side effects. While there are series that report that the most prevalent adverse effects are diarrhea, nausea, rash and alopecia, there are few reported cases of alopecia universalis secondary to the use of leflunomide. We present a case in the Regional Hospital of Talca and a review of the use of leflunomide. PMID- 26819062 TI - Characterizing redescriptions using persistent homology to isolate genetic pathways contributing to pathogenesis. AB - BACKGROUND: Complex diseases may have multiple pathways leading to disease. E.g. coronary artery disease evolves from arterial damage to their epithelial layers, but has multiple causal pathways. More challenging, those pathways are highly correlated within metabolic syndrome. The challenge is to identify specific clusters of phenotype characteristics (composite phenotypes) that may reflect these different etiologies. Further, GWAS seeking to identify SNPs satisfying multiple composite phenotype descriptions allows for lower false positive rates at lower alpha thresholds, allowing for the possibility of reducing false negatives. This may provide a window into the missing heritability problem. METHODS: We identify significant phenotype patterns, and identify fuzzy redescriptions among those patterns using Jaccard distances. Further, we construct Vietoris-Rips complexes from the Jaccard distances and compute the persistent homology associated with those. The patterns comprising these topological features are identified as composite phenotpyes, whose genetic associations are explored with logistic regression applied to pathways and to GWAS. RESULTS: We identified several phenotypes that tended to be dominated by metabolic syndrome descriptions, and which were distinct among the combinations of metabolic syndrome conditions. Among SNPs marking the RAAS complex, various SNPs associated specifically with different groups of composite phenotypes, as well as distinguishing between the composite phenotypes and simple phenotypes. Each of these showed different genetic associations, namely rs6693954, rs762551, rs1378942, and rs1133323. GWAS identified SNPs that associated with composite phenotypes included rs12365545, rs6847235, and rs701319. Eighteen GWAS identified SNPs appeared in combinations supported in composite combinations with greater power than for any individual phenotype. CONCLUSIONS: We do find systematic associations among metabolic syndrome variates that show distinctive genetic association profiles. Further, the systematic characterization involves composite phenotype descriptions that allow for combined power of individual phenotype GWAS tests, yielding more significance for lower individual thresholds, permitting the exploration of SNPs that would otherwise show as false negatives. PMID- 26819064 TI - The Laschamp geomagnetic excursion featured in nitrate record from EPICA-Dome C ice core. AB - Here we present the first direct comparison of cosmogenic (10)Be and chemical species in the period of 38-45.5 kyr BP spanning the Laschamp geomagnetic excursion from the EPICA-Dome C ice core. A principal component analysis (PCA) allowed to group different components as a function of the main sources, transport and deposition processes affecting the atmospheric aerosol at Dome C. Moreover, a wavelet analysis highlighted the high coherence and in-phase relationship between (10)Be and nitrate at this time. The evident preferential association of (10)Be with nitrate rather than with other chemical species was ascribed to the presence of a distinct source, here labelled as "cosmogenic". Both the PCA and wavelet analyses ruled out a significant role of calcium in driving the (10)Be and nitrate relationship, which is particularly relevant for a plateau site such as Dome C, especially in the glacial period during which the Laschamp excursion took place. The evidence that the nitrate record from the EDC ice core is able to capture the Laschamp event hints toward the possibility of using this marker for studying galactic cosmic ray flux variations and thus also major geomagnetic field excursions at pluri-centennial-millennial time scales, thus opening up new perspectives in paleoclimatic studies. PMID- 26819063 TI - Consumption and reasons for use of dietary supplements in an Australian university population. AB - OBJECTIVE: The aim of this study was to examine the association between dietary supplement use and sociodemographic factors in an Australian university population. Additionally, reasons for use of specific dietary supplements were explored. METHODS: A cross-sectional online questionnaire was completed by 1633 students and staff members of Griffith University, Queensland, Australia (76% female). The questionnaire collected information on sociodemographic characteristics, use of dietary supplements, and reasons for use of each dietary supplement reported. Multiple regression analyses were used to describe the relationship between demographic factors and dietary supplement use. Pearson chi(2) was used to identify correlations between frequency of dietary supplement use and selected demographic factors. Frequency distributions were used to explore the reasons for use of each dietary supplement reported. RESULTS: Vitamin or mineral use and use of "other" dietary supplements was reported by 69% and 63% of participants, respectively. Age, sex, ethnicity, and physical activity were independently associated with dietary supplement use. Age, sex, and income were associated with acute use of specific dietary supplements during illness or injury. The reasons for use of specific dietary supplements were closely aligned with marketed claims. Broad reasons of health were commonly reported for use of most dietary supplements. CONCLUSIONS: Use of dietary supplements in this population reflects that of other countries. Individuals were unsure of the benefits and risks associated with dietary supplementation. Health professionals should account for dietary supplements when assessing diet. These results also warrant consideration by regulating bodies and public health officers to ensure safe practices. PMID- 26819065 TI - Assessment of cardiovascular disease risk factors in a genetically homogenous population of Parsi Zoroastrians in the United States: A pilot study. AB - OBJECTIVE: Genetically isolated and homogenous populations are ideal for detecting genes underlying common complex diseases. The use of isolated populations with reduced disease heterogeneity has led to significant gene discoveries in the past. The aim of this pilot study was to assess the prevalence of cardiovascular disease (CVD) risk phenotypes in a genetically homogenous population of Parsi Zoroastrians in the United States. METHODS: Anthropometrics, blood pressure, and medical history were collected from 152 men and 186 women participating in a pilot study as part of the Parsi Family Study. The relative pairs used in the study included 60 parent-off springs, 28 siblings, 6 grandparent-grandchild, 7 avuncular, 18 half-siblings, 7 half-avuncular, and one half-first cousin. Estimates of genetic and environmental influence were calculated using a maximum likelihood-based variance components method implemented in SOLAR. RESULTS: The prevalence of overweight/obesity in adults (62%) was on par with current US prevalence. Hypertension and prehypertension were prevalent in 16% and 46% of the participants, respectively. The quantitative genetic analysis revealed significant heritabilities for all anthropometric phenotypes (P < 0.05). Significant phenotypic correlations were found between blood pressure and anthropometric phenotypes (P < 0.001), whereas significant genetic correlation was found for only diastolic blood pressure and fat free mass (rhoG = -0.88, P < 0.05). CONCLUSION: These preliminary data show significant additive genetic effects on CVD-related phenotypes in this population. Our findings represent the first epidemiological data in Parsi Zoroastrians in the United States and offer excellent promise for future genetic studies in this population. Am. J. Hum. Biol. 28:440-443, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26819066 TI - Incomplete Disclosure of Potential Conflicts of Interest. PMID- 26819067 TI - Psychiatrist is charged after 12 patient deaths. PMID- 26819068 TI - Post-transcriptionally generated cell heterogeneity regulates biofilm formation in Bacillus subtilis. AB - Bacillus subtilis forms biofilms in appropriate environments by producing extracellular matrices. Genes required for matrix formation, for example tapA, are regulated by the SinI/SinR/SlrR system. SinR is the repressor for tapA. SinI and SlrR inhibit DNA-binding of SinR. sinI and sinR constitute two-gene operon, and sinR has its own promoter. During biofilm formation, a portion of the population differentiates into matrix-producing cells. This is thought to be caused by Spo0A-dependent, heterogeneous expression of the PsinI promoter, whereas the PsinR promoter is expressed homogeneously. However, we observed that at its original locus, overall sinI transcription was almost homogeneous, because upstream read-through transcription from PyqHG would overcome expression of PsinI. When we used translational sinI-gfp and sinR-mCherry reporters at their original loci, their fluorescence distribution patterns in the cell population were clearly bimodal. This bimodal expression might be caused by cell-to-cell variations of mRNA stability. This study shows that the post-transcriptionally regulated bimodal expression of SinI and SinR is important for bacterial cell fate determination. PMID- 26819069 TI - Highly efficient siRNA delivery from core-shell mesoporous silica nanoparticles with multifunctional polymer caps. AB - A new general route for siRNA delivery is presented combining porous core-shell silica nanocarriers with a modularly designed multifunctional block copolymer. Specifically, the internal storage and release of siRNA from mesoporous silica nanoparticles (MSN) with orthogonal core-shell surface chemistry was investigated as a function of pore-size, pore morphology, surface properties and pH. Very high siRNA loading capacities of up to 380 MUg per mg MSN were obtained with charge matched amino-functionalized mesoporous cores, and release profiles show up to 80% siRNA elution after 24 h. We demonstrate that adsorption and desorption of siRNA is mainly driven by electrostatic interactions, which allow for high loading capacities even in medium-sized mesopores with pore diameters down to 4 nm in a stellate pore morphology. The negatively charged MSN shell enabled the association with a block copolymer containing positively charged artificial amino acids and oleic acid blocks, which acts simultaneously as capping and endosomal release agent. The potential of this multifunctional delivery platform is demonstrated by highly effective cell transfection and siRNA delivery into KB cells. A luciferase reporter gene knock-down of up to 80-90% was possible using extremely low cell exposures with only 2.5 MUg MSN containing 0.5 MUg siRNA per 100 MUL well. PMID- 26819070 TI - Evaluation of a multifunctional technology system in a memory care unit: Opportunities for innovation in dementia care. AB - INTRODUCTION: Stimulating recreational and leisure activities (RLAs) are essential to physical and mental well-being; however, people living in memory care units (MCUs) may lack access to them. Technology has the potential to facilitate and enrich activity engagement in this context. OBJECTIVES: In this 6 month study, we evaluated a commercially available system designed to encourage the engagement of people with dementia in activities and social interactions, using a mixed-methods approach in a MCU. METHODS: Quantitative measures included those to evaluate cognition, depression, quality of life, and resource utilization. We qualitatively evaluated the system using semi-structured interviews with family members and staff. Five residents with dementia, four family members, and seven staff were included in the 6-month study. RESULTS: Staff and family members reported benefits for residents such as enjoyment, interactions and connections with others, and mental stimulation. Findings also highlight challenges such as technical and ethical concerns. Factors that influence system use and integration are also discussed. CONCLUSION: It was feasible to introduce a system designed for recreation and engagement in a MCU, and staff, family members, and residents experienced benefits. However, barriers existed in the introduction and use of the system. PMID- 26819071 TI - Sex differences in amygdala shape: Insights from Turner syndrome. AB - OBJECTIVE: Sex differences in the manifestation of psychiatric disorders, including anxiety disorders, are among the most prominent findings in psychiatry. The study of Turner syndrome (TS), caused by X-monosomy, has the potential to reveal mechanisms that underline male/female differences in neuropsychiatric disorders. The amygdala has been implicated in numerous neuropsychiatric disorders. Previous studies suggest an effect of TS on amygdala volume as well as on amygdala-related behaviors such as anxiety. Our objective is to investigate the amygdala shape in TS. Specifically, we tested whether amygdala enlargements in TS are localized to specific nuclei implicated in anxiety, such as the basomedial nucleus. EXPERIMENTAL DESIGN: We use a surface-based analytical modeling approach to contrast 41 pre-estrogen treatment girls with TS (mean age 8.6 +/- 2.4) with 34 age-and sex-matched typically developing (TD) controls (mean age 8.0 +/- 2.8). Anxiety symptoms were assessed using the Revised Children's Manifest Anxiety Scale - 2 (RCMAS-2) in both groups. PRINCIPAL OBSERVATIONS: TS was associated with anomalous enlargement of the amygdala. Surface-based modeling revealed shape differences (increased radial-distances) in bilateral basal and basomedial nuclei within the basolateral complex. RCMAS-2 Total Anxiety t-score was significantly higher in participants with TS compared with TD controls (P = 0.012). CONCLUSIONS: Group differences in global amygdala volumes were driven by local morphological increases in areas that are critically involved in face emotion processing and anxiety. In the context of increased amygdala volumes in TS, our results also showed increased worry and social anxiety in young girls with TS compared with TD. PMID- 26819072 TI - Oral propranolol combined with topical timolol for compound infantile hemangiomas: a retrospective study. AB - Compound infantile hemangiomas (IHs) are problematic and usually require intervention. This retrospective study aimed to introduce a combined therapy of oral propranolol and topical timolol, and evaluate its efficacy and safety. Eighty-nine infants with compound IHs were treated with oral propranolol 2 mg/kg/day divided 2 times per day and timolol maleate 0.5% gel 3 times per day, for at least 3 months. Two observers evaluated the hemangioma independently at 0, 1, 3, 6, 9 months after the initiation of treatment. Changes in the hemangioma score values were evaluated using paired t test. Rebound growth and adverse effects were recorded. After treatment was completed, this combined therapy achieved clinical response in 100% of the patients (89/89). Significant positive effects were demonstrated at 1, 3, 6 months (p < 0.001), but not obvious after 6 months (p = 0.06). The response of IHs to the therapy was depending on the age at initial treatment. The average treatment duration was 6.48 (5.77-7.19) months. One patient (1.1%) relapsed after cessation of 6-month treatment, and 7 children (7.8%) developed side effects. Our study suggested that oral propranolol combined with topical timolol treatment is very effective and well-tolerated for compound IHs, which can be used as a first line treatment. PMID- 26819073 TI - Influence of betaine and arginine supplementation of reduced protein diets on fatty acid composition and gene expression in the muscle and subcutaneous adipose tissue of cross-bred pigs. AB - The isolated or combined effects of betaine and arginine supplementation of reduced protein diets (RPD) on fat content, fatty acid composition and mRNA levels of genes controlling lipid metabolism in pig m. longissimus lumborum and subcutaneous adipose tissue (SAT) were assessed. The experiment was performed on forty intact male pigs (Duroc*Large White*Landrace cross-breed) with initial and final live weights of 60 and 93 kg, respectively. Pigs were randomly assigned to one of the following five diets (n 8): 16.0 % of crude protein (control), 13.0 % of crude protein (RPD), RPD supplemented with 0.33 % of betaine, RPD supplemented with 1.5 % of arginine and RPD supplemented with 0.33 % of betaine and 1.5 % of arginine. Data confirmed that RPD increase intramuscular fat (IMF) content and total fat content in SAT. The increased total fat content in SAT was accompanied by higher GLUT type 4, lipoprotein lipase and stearoyl-CoA desaturase mRNA expression levels. In addition, the supplementation of RPD with betaine and/or arginine did not affect either IMF or total fat in SAT. However, dietary betaine supplementation slightly affected fatty acid composition in both muscle and SAT. This effect was associated with an increase of carnitine O-acetyltransferase mRNA levels in SAT but not in muscle, which suggests that betaine might be involved in the differential regulation of some key genes of lipid metabolism in pig muscle and SAT. Although the arginine-supplemented diet decreased the mRNA expression level of PPARG in muscle and SAT, it did not influence fat content or fatty acid composition in any of these pig tissues. PMID- 26819074 TI - Gradual improvement of hyperammonemic hepatic encephalopathy after the extirpation of a large uterine leiomyoma in a woman with constipation and liver cirrhosis resulting from autoimmune hepatitis. AB - There have been few reports regarding the improvement of hyperammonemic hepatic encephalopathy after the extirpation of a large uterine leiomyoma. We present a case of a 53-year-old postmenopausal woman who experienced a clouding of consciousness. She had been suffering from mild hepatitis and a large uterine leiomyoma. On admission, she had experienced constipation for seven days and exhibited a high serum ammonia level (251 MUg/dL). She was diagnosed with liver cirrhosis as a result of autoimmune hepatitis, combined with Sjogren's syndrome. A total hysterectomy was performed 29 days after admission. Severe diarrhea lasted for three days after surgery. By the sixth postoperative day, the patient's consciousness level had normalized and her serum ammonia level had fallen to 47 MUg/dL. Although the true mechanism of hyperammonemia in this case is unclear, we speculate that organic constipation following chronic obstruction of the colon might have played a role in the development of the condition. PMID- 26819075 TI - On the road to personalised and precision geomedicine: medical geology and a renewed call for interdisciplinarity. AB - Our health depends on where we currently live, as well as on where we have lived in the past and for how long in each place. An individual's place history is particularly relevant in conditions with long latency between exposures and clinical manifestations, as is the case in many types of cancer and chronic conditions. A patient's geographic history should routinely be considered by physicians when diagnosing and treating individual patients. It can provide useful contextual environmental information (and the corresponding health risks) about the patient, and should thus form an essential part of every electronic patient/health record. Medical geology investigations, in their attempt to document the complex relationships between the environment and human health, typically involve a multitude of disciplines and expertise. Arguably, the spatial component is the one factor that ties in all these disciplines together in medical geology studies. In a general sense, epidemiology, statistical genetics, geoscience, geomedical engineering and public and environmental health informatics tend to study data in terms of populations, whereas medicine (including personalised and precision geomedicine, and lifestyle medicine), genetics, genomics, toxicology and biomedical/health informatics more likely work on individuals or some individual mechanism describing disease. This article introduces with examples the core concepts of medical geology and geomedicine. The ultimate goals of prediction, prevention and personalised treatment in the case of geology-dependent disease can only be realised through an intensive multiple-disciplinary approach, where the various relevant disciplines collaborate together and complement each other in additive (multidisciplinary), interactive (interdisciplinary) and holistic (transdisciplinary and cross disciplinary) manners. PMID- 26819058 TI - The European Hematology Association Roadmap for European Hematology Research: a consensus document. AB - The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at ?23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap.The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders.The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. PMID- 26819076 TI - Low-dose cisplatin-induced CXCR4 expression promotes proliferation of ovarian cancer stem-like cells. AB - Chemoresistance blocks the efficient treatment of epithelial ovarian cancer, which is the most lethal of all gynecological cancers. Cancer stem cells are believed to be at least partially responsible for the development of chemoresistance. In this study, the effect of cisplatin (CDP) on the enrichment and proliferation of cancer stem-like cells (CSLCs) was investigated, and the underlying mechanisms of action were elucidated. An in vitro anchor-free system was employed to enrich CSLCs from the SKOV3 human epithelial ovarian cancer cell line. Our results showed that treatment with low concentrations of CDP resulted in better-enriched CSLCs, with higher proliferative activities. Low dose of CDP was found to induce the expression of chemokine (C-X-C motif) receptor 4 (CXCR4), which is an important stemness marker in cancer stem cells as well as a promising therapeutic target for ovarian cancer treatment. Results also showed that overexpressed CXCR4 generated chemoresistance. Based on these results, it may be concluded that, at low concentrations, CDP itself contributes to the development of drug resistance. This finding provides novel insight into the mechanisms underlying chemoresistance and has significant therapeutic implications for epithelial ovarian cancer treatment. PMID- 26819077 TI - Consensus on Surgical Management of Hallux Valgus from China. AB - Hallux valgus deformity is one of the most common diseases in foot and ankle surgery. Satisfactory outcomes tend to be achieved only through operative correction. However, selection of the optimal surgical strategy is always a controversial topic, and the rate of dissatisfied patients postoperativelyis still very high. It is well known that there are various pathological changes in hallux valgus deformity, so it is impossible to use one specific procedure to solve all the problems. It requires a careful preoperative physical examination and radiographic assessment to choose the best operation for each kind of deformity according to each pathalogical change, combined with good postoperative dressing, immobilization and proper rehabilitation and follow up, to improve surgical outcomes and reduce postoperative rate of complication and dissatisfaction. In order to achieve these goals, a Consensus on the Operative Correction of Hallux Valgus has been developed by the Foot and Ankle Working Committee, Orthopaedic Branch, Chinese Association of Orthopaedic Surgeons. Foot and ankle surgeons following this consensus must be fully aware of their patients' desires, carefully evaluate different pathological processes and clinical symptoms and be skilled in various procedures. Then these procedures can be easily selected, converted and combined based on preoperative plans and intraoperative conditions. PMID- 26819078 TI - Clinical significance of multi-leaf collimator calibration errors. AB - This planning study investigates the clinical impact of multi-leaf collimator (MLC) calibration errors on three common treatment sites; head and neck (H&N), prostate and stereotactic body radiotherapy (SBRT) for lung. All plans used using either volumetric modulated adaptive therapy or dynamic MLC techniques. Five patient plans were retrospectively selected from each treatment site, and MLC errors intentionally introduced. MLC errors of 0.7, 0.4 and 0.2 mm were sufficient to cause major violations in the PTV planning criteria for the H&N, prostate and SBRT lung plans. Mean PTV dose followed a linear trend with MLC error, increasing at rates of 3.2-5.9% per millimeter depending on treatment site. The results indicate that an MLC quality assurance program that provides sub-millimeter accuracy is an important component of intensity modulated radiotherapy delivery techniques. PMID- 26819080 TI - Q&A: How do plants respond to ethylene and what is its importance? AB - Ethylene gas is a major plant hormone that influences diverse processes in plant growth, development and stress responses throughout the plant life cycle. Responses to ethylene, such as fruit ripening, are significant to agriculture. The core molecular elements of the ethylene-signaling pathway have been uncovered, revealing a unique pathway that is negatively regulated. Practical applications of this knowledge can lead to substantial improvements in agriculture. PMID- 26819079 TI - Socioeconomic and sociodemographic factors related to allergic diseases in Korean adolescents based on the Seventh Korea Youth Risk Behavior Web-based Survey: a cross-sectional study. AB - BACKGROUND: Various international reports have shown that socioeconomic and sociodemographic variables are correlated with allergic diseases; however, little is known about how these variables affect Korean adolescents. This study was conducted to identify socioeconomic and sociodemographic risk factors for allergic diseases in Korean adolescents to provide information for preventing and managing such conditions. METHODS: Data from the 2011 Korea Youth Risk Behavior Web-based Survey (KYRBWS-VII) of 75,643 adolescents were used. An anonymously administered online survey was conducted to collect dependent variable information on perceived sexes, residence, family affluence (Family Affluence Scale; FAS), parental education levels, subjective academic achievement, obesity, drinking and smoking. The independent variables were asthma, allergic rhinitis and atopic dermatitis. Multivariate logistic regression was used to analyze the correlations between the dependent and independent variables. RESULTS: Low subjective academic achievement, obesity, drinking and smoking were risk factors for asthma. High FAS, parental bachelor's degree and high subjective academic achievement were risk factors for allergic rhinitis. Finally, high FAS, maternal bachelor's degree and high subjective academic achievement were risk factors for atopic dermatitis. CONCLUSION: We found that high socioeconomic status (SES) was a risk factor for allergic diseases in Korean adolescents. We propose that the greater access to medical services and immunization (e.g., hygiene hypothesis) afforded by high SES influenced the prevalence of allergic diseases. Thus, as the Korean economy develops further, the prevalence of allergic diseases is likely to increase. Controlling harmful behavioral risk factors, such as drinking and smoking, may help to prevent adolescent allergic diseases. PMID- 26819082 TI - Narcissistic personality and risk perception among Chinese aviators: The mediating role of promotion focus. AB - Optimism bias is a crucial feature of risk perception that leads to increased risk-taking behaviour, which is a particularly salient issue among pilots in aviation settings due to the high-stakes nature of flight. The current study sought to address the roles of narcissism and promotion focus on optimism bias in risk perception in aviation context. Participants were 239 male flight cadets from the Civil Aviation Flight University of China who completed the Narcissistic Personality Inventory-13, the Work Regulatory Focus Scale, and an indirect measure of unrealistic optimism in risk perception, which measured risk perception for the individual and the risk assumed by other individuals performing the same task. Higher narcissism increased the likelihood of underestimating personal risks, an effect that was mediated by high promotion focus motivation, such that high narcissism led to high promotion focus motivation. The findings have important implications for improving the accuracy of risk perception in aviation risks among aviators. PMID- 26819081 TI - Quantitative assessment of the association between Fas/FasL gene polymorphism and susceptibility to esophageal carcinoma in a north Chinese population. AB - The case-control study aims to investigate the association of Fas and FasL genetic polymorphisms (Fas-670A/G (rs1800682), Fas-1377G/A (rs2234767) and FasL 844T/C (rs763110)) with esophageal carcinoma susceptibility in a north Chinese population. A total of 204 patients with esophageal carcinoma and 248 healthy controls were enrolled from Henan, China and genotyped by the polymerase chain reaction and restriction fragment length polymorphism method. There were no significant differences in distributions of their genotypes frequencies between patients and controls in Fas-670A/G, Fas-1377G/A and FasL-844T/C polymorphisms (P > 0.05). Stratified analysis showed that no significant association was found between esophageal carcinoma and gene polymorphisms of Fas-670 A/G, Fas-1377G/A, and FasL-844T/C (P > 0.05). Genetic polymorphisms in the death pathway genes Fas and FasL were not associated with risk of developing esophageal carcinoma in a north Chinese population. PMID- 26819083 TI - Innovative Application of Mechanical Activation for Rare Earth Elements Recovering: Process Optimization and Mechanism Exploration. AB - With the rapidly expanding use of fluorescent lamps (FLs) and increasing interest in conservation and sustainable utilization of critical metals such as rare earth elements (REEs), the recovering of REEs from phosphors in waste FLs is becoming a critical environmental and economic issue. To effectively recycle REEs with metallurgical methods, mechanical activation by ball milling was introduced to pretreat the waste phosphors. This current study put the emphasis on the mechanical activation and leaching processes for REEs, and explored the feasibility of the method from both theoretical and practical standpoints. Results showed physicochemical changes of structural destruction and particle size reduction after mechanical activation, leading to the easy dissolution of REEs in the activated samples. Under optimal conditions, dissolution yields of 89.4%, 93.1% and 94.6% for Tb, Eu and Y, respectively, were achieved from activated waste phosphors using hydrochloric acid as the dissolution agent. The shrinking core model proved to be the most applicable for the leaching procedure, with an apparent activation energy of 10.96 +/- 2.79 kJ/mol. This novel process indicates that mechanical activation is an efficient method for recovering REEs from waste phosphors, and it has promising potential for REE recovery with low cost and high efficiency. PMID- 26819084 TI - Suppression of pancreatic beta cell apoptosis by Danzhi Jiangtang capsule contributes to the attenuation of type 1 diabetes in rats. AB - BACKGROUND: Danzhi Jiangtang Capsule (DJC), a Chinese medicinal formula, has been clinically used for treatment of diabetes for many years. Previous studies have demonstrated that DJC was able to improve pancreatic islet function in diabetes, but the underlying mechanisms remained unclear. METHODS: Streptozotocin (STZ) induced type 1 diabetic rats were treated with DJC for 6 weeks. Fasting plasma insulin and fasting plasma glucose were determined at the end of experiment. Antioxidant status was evaluated by measuring total antioxidant capacity, superoxide dismutase activity and malondialdehyde content in plasma and pancreas. Paraffin sections of pancreas were subjected to H&E staining, TUNEL staining and immunohistochemical examination. Protein levels of Bcl-2, Bax and pancreatic duodenal homeobox-1 (PDX-1) were measured by western blot analysis. Activities of Caspase-3 and Caspase-9 were determined with commercially available kits. RESULTS: Supplementation with DJC resulted in a significant amelioration of type 1 diabetes as manifested by reduced blood glucose, increased fasting plasma insulin and improved body weight gains. The atrophy and reduction of pancreatic islets were also alleviated in DJC supplemented groups. DJC markedly reduced pancreatic beta cell apoptosis, with Bax protein down-regulated and Bcl-2 protein up-regulated significantly. The activities of caspase-3 and caspase-9 in pancreas were decreased evidently by DJC treatment. DJC effectively ameliorated oxidative stress in type 1 diabetic rats, with the expression of PDX-1 protein increased markedly. CONCLUSIONS: DJC was capable of attenuating STZ induced type 1 diabetes in rats, which might be attributed to the suppression of pancreatic beta cell apoptosis. This study would provide further evidence for clinical use of DJC in the management of diabetes. PMID- 26819085 TI - Label-Free Fluctuation Spectroscopy Based on Coherent Anti-Stokes Raman Scattering from Bulk Water Molecules. AB - Nanoparticles (NPs) and molecules can be analyzed by inverse fluorescence correlation spectroscopy (iFCS) as they pass through an open detection volume, displacing fractions of the fluorescence-emitting solution in which they are dissolved. iFCS does not require the NPs or molecules to be labeled. However, fluorophores in MUm-mm concentrations are needed for the solution signal. Here, we instead use coherent anti-Stokes Raman scattering (CARS) from plain water molecules as the signal from the solution. By this fully label-free approach, termed inverse CARS-based correlation spectroscopy (iCARS-CS), NPs that are a few tenths of nm in diameter and at pM concentrations can be analyzed, and their absolute volumes/concentrations can be determined. Likewise, lipid vesicles can be analyzed as they diffuse/flow through the detection volume by using CARS fluctuations from the surrounding water molecules. iCARS-CS could likely offer a broadly applicable, label-free characterization technique of, for example, NPs, small lipid exosomes, or microparticles in biomolecular diagnostics and screening, and can also utilize CARS signals from biologically relevant media other than water. PMID- 26819086 TI - Construction and evaluation of a novel bifunctional phenylalanine-formate dehydrogenase fusion protein for bienzyme system with cofactor regeneration. AB - Phenylalanine dehydrogenase (PheDH) plays an important role in enzymatic synthesis of L-phenylalanine for aspartame (sweetener) and detection of phenylketonuria (PKU), suggesting that it is important to obtain a PheDH with excellent characteristics. Gene fusion of PheDH and formate dehydrogenase (FDH) was constructed to form bifunctional multi-enzymes for bioconversion of L phenylalanine coupled with coenzyme regeneration. Comparing with the PheDH monomer from Microbacterium sp., the bifunctional PheDH-FDH showed noteworthy stability under weakly acidic and alkaline conditions (pH 6.5-9.0). The bifunctional enzyme can produce 153.9 mM L-phenylalanine with remarkable performance of enantiomers choice by enzymatic conversion with high molecular conversion rate (99.87 %) in catalyzing phenylpyruvic acid to L-phenylalanine being 1.50-fold higher than that of the separate expression system. The results indicated the potential application of the PheDH and PheDH-FDH with coenzyme regeneration for phenylpyruvic acid analysis and L-phenylalanine biosynthesis in medical diagnosis and pharmaceutical field. PMID- 26819087 TI - Chrysanthemum transcription factor CmLBD1 direct lateral root formation in Arabidopsis thaliana. AB - The plant-specific LATERAL ORGAN BOUNDARIES DOMAIN (LBD) genes are important regulators of growth and development. Here, a chrysanthemum class I LBD transcription factor gene, designated CmLBD1, was isolated and its function verified. CmLBD1 was transcribed in both the root and stem, but not in the leaf. The gene responded to auxin and was shown to participate in the process of adventitious root primordium formation. Its heterologous expression in Arabidopsis thaliana increased the number of lateral roots formed. When provided with exogenous auxin, lateral root emergence was promoted. CmLBD1 expression also favored callus formation from A. thaliana root explants in the absence of exogenously supplied phytohormones. In planta, CmLBD1 probably acts as a positive regulator of the response to auxin fluctuations and connects auxin signaling with lateral root formation. PMID- 26819090 TI - Exploration of Gate-Opening and Breathing Phenomena in a Tailored Flexible Metal Organic Framework. AB - Flexible metal-organic frameworks (MOFs) show the structural transition phenomena, gate opening and breathing, upon the input of external stimuli. These phenomena have significant implications in their adsorptive applications. In this work, we demonstrate the direct capture of these gate-opening and breathing phenomena, triggered by CO2 molecules, in a well-designed flexible MOF composed of rotational sites and molecular gates. Combining X-ray single crystallographic data of a flexible MOF during gate opening/closing and breathing with in situ X ray powder diffraction results uncovered the origin of this flexibility. Furthermore, computational studies revealed the specific sites required to open these gates by interaction with CO2 molecules. PMID- 26819088 TI - Identification of molecular signatures specific for distinct cranial sensory ganglia in the developing chick. AB - BACKGROUND: The cranial sensory ganglia represent populations of neurons with distinct functions, or sensory modalities. The production of individual ganglia from distinct neurogenic placodes with different developmental pathways provides a powerful model to investigate the acquisition of specific sensory modalities. To date there is a limited range of gene markers available to examine the molecular pathways underlying this process. RESULTS: Transcriptional profiles were generated for populations of differentiated neurons purified from distinct cranial sensory ganglia using microdissection in embryonic chicken followed by FAC-sorting and RNAseq. Whole transcriptome analysis confirmed the division into somato- versus viscerosensory neurons, with additional evidence for subdivision of the somatic class into general and special somatosensory neurons. Cross comparison of distinct ganglia transcriptomes identified a total of 134 markers, 113 of which are novel, which can be used to distinguish trigeminal, vestibulo acoustic and epibranchial neuronal populations. In situ hybridisation analysis provided validation for 20/26 tested markers, and showed related expression in the target region of the hindbrain in many cases. CONCLUSIONS: One hundred thirty four high-confidence markers have been identified for placode-derived cranial sensory ganglia which can now be used to address the acquisition of specific cranial sensory modalities. PMID- 26819089 TI - Epigenetic regulation of E-cadherin expression by the histone demethylase UTX in colon cancer cells. AB - Decreased epithelial cadherin (E-cadherin) gene expression, a hallmark of epithelial-mesenchymal transition (EMT), is essential for triggering metastatic advantage of the colon cancer. Genetic mechanisms underlying the regulation of E cadherin expression in EMT have been extensively investigated; however, much is unknown about the epigenetic mechanism underlying this process. Here, we identified ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX), a histone demethylase involved in demethylating di- or tri-methylated histone 3 lysine 27 (H3K27me2/3), as a positive regulator for the expression of E cadherin in the colon cancer cell line HCT-116. We showed that inactivation of UTX down-regulated E-cadherin gene expression, while overexpression of UTX did the opposite. Notably, overexpression of UTX inhibited migration and invasion of HCT-116 cells. Moreover, UTX demethylated H3K27me3, a histone transcriptional repressive mark, leading to decreased H3K27me3 at the E-cadherin promoter. Further, UTX interacted with the histone acetyltransferase (HAT) protein CBP and recruited it to the E-cadherin promoter, resulting in increased H3K27 acetylation (H3K27ac), a histone transcriptional active mark. UTX positively regulates E cadherin expression through coordinated regulation of H3K27 demethylation and acetylation, switching the transcriptional repressive state to the transcriptional active state at the E-cadherin promoter. We conclude that UTX may play a role in regulation of E-cadherin gene expression in HCT-116 cells and that UTX may serve as a therapeutic target against the metastasis in the treatment of colon cancer. PMID- 26819092 TI - Solubilisation and chemical fixation of copper(II) in micronized copper treated wood. AB - Wood preservatives using micronized particulate copper as the main active ingredient recently introduced in the USA have generated controversies due to their limited intrinsic solubility compared to the conventional soluble copper treatments. Because the availability of soluble copper ions is essential for these preservatives to provide an effective treatment, concerns centered on whether they are able to produce soluble copper when introduced into wood, and the copper fixation mechanism of the treatment is little understood. A combination of Electron Paramagnetic Resonance (EPR) spectroscopy and X-ray Fluorescence (XRF) spectroscopy has been successfully utilized to characterize and quantify solubilized and fixed copper species in micronized copper treated wood, which also contains unreacted particulate copper. On the basis of the experimental results, the fixation mechanism is thought to be triggered by the reaction between the carboxylic acid protons in hemicellulose of wood with the particulate copper, and the quantities of the solubilized and fixed copper species are determined by the availability of these acidic protons. PMID- 26819091 TI - Characterization of a novel adult murine immortalized microglial cell line and its activation by amyloid-beta. AB - BACKGROUND: Alzheimer's disease is associated with amyloid-beta (Abeta)-induced microglia activation. This pro-inflammatory response promotes neuronal damage, and therapies are sought to limit microglial activation. Screening efforts to develop new pharmacological inhibitors require a robust in vitro cell system. Current models lack significant responses to Abeta, and their use in examining age-related neurodegenerative diseases is questionable. For example, the commonly used BV-2 microglial line was derived from embryonic mononuclear cells and its activation by various stimuli is limited. To this end, we have established a new immortalized microglial (IMG) cell line from adult murine brain. The objective of this study was to characterize Abeta-induced activation of IMG cells, and here, we demonstrate the ability of cannabinoids to significantly reduce this inflammatory response. METHODS: Microglial cells derived from adult murine brain were immortalized via infection with the v-raf/v-myc retrovirus under conditions that selectively promote microglia growth. The presence or absence of markers CD11b and F4/80 (microglial), NeuN (neuronal), and GFAP (astrocytic) was assessed by immunofluorescence microscopy and western blotting. Using IMG and BV-2 cells, levels of pro- and anti-inflammatory transcripts in response to extracellular stimuli were determined by quantitative PCR (qPCR). Phagocytosis of fluorescent beads and fluorescein isothiocyanate (FITC)-labeled Abeta oligomers was assessed using flow cytometry and fluorescence microscopy. FITC-Abeta uptake was quantified using a fluorescence plate reader. The ability of cannabinoids to mitigate Abeta-induced expression of inducible nitric oxide synthase (iNOS) was evaluated. RESULTS: IMG cells express the microglial markers CD11b and F4/80 but not NeuN or GFAP. Relative to BV-2 cells, IMG cells increased iNOS (>200-fold) and Arg-1 (>100-fold) in response to pro- and anti-inflammatory stimuli. IMG cells phagocytose foreign particles and Abeta oligomers, with the latter trafficked to phagolysosomes. Abeta-induced activation of IMG cells was suppressed by delta-9-tetrahydrocannabinol and the CB2-selective agonist JWH-015 in a time- and concentration-dependent manner. CONCLUSIONS: IMG cells recapitulate key features of microglial cell activation. As an example of their potential pharmacological use, cannabinoids were shown to reduce activation of Abeta-induced iNOS gene expression. IMG cells hold promising potential for drug screening, mechanistic studies, and functional investigations directed towards understanding how Abeta interacts with microglia. PMID- 26819093 TI - Atypical Leber Hereditary Optic Neuropathy: 18 Year Interval Between Eyes. AB - A 5-year-old boy developed profound loss of vision in his right eye and was found to have a 11778 mitochondrial point mutation consistent with Leber hereditary optic neuropathy (LHON). He maintained 20/20 vision in the left eye for 18 years until age 23, when he experienced loss of vision in that eye. This 18 year interval between eye involvement in LHON is the longest reported to date and reinforces the variability in presentation and progression seen in this disease. PMID- 26819094 TI - A maximum-likelihood approach for building cell-type trees by lifting. AB - BACKGROUND: In cell differentiation, a less specialized cell differentiates into a more specialized one, even though all cells in one organism have (almost) the same genome. Epigenetic factors such as histone modifications are known to play a significant role in cell differentiation. We previously introduce cell-type trees to represent the differentiation of cells into more specialized types, a representation that partakes of both ontogeny and phylogeny. RESULTS: We propose a maximum-likelihood (ML) approach to build cell-type trees and show that this ML approach outperforms our earlier distance-based and parsimony-based approaches. We then study the reconstruction of ancestral cell types; since both ancestral and derived cell types can coexist in adult organisms, we propose a lifting algorithm to infer internal nodes. We present results on our lifting algorithm obtained both through simulations and on real datasets. CONCLUSIONS: We show that our ML-based approach outperforms previously proposed techniques such as distance based and parsimony-based methods. We show our lifting-based approach works well on both simulated and real data. PMID- 26819096 TI - Neurotrophic keratopathy secondary to trigeminal nerve aplasia in patient with Goldenhar syndrome. AB - CASE REPORT: A 4-year-old male diagnosed with Goldenhar syndrome, with an unremarkable ophthalmic history, develops a neurotrophic ulcer secondary to trigeminal nerve aplasia. It was treated with multilaminar amniotic membrane transplantation. DISCUSSION: Trigeminal nerve aplasia is not usually reported in Goldenhar syndrome. Therefore, it seems necessary to perform routine eye examinations, from an early age, to prevent serious complications associated with corneal anaesthesia. PMID- 26819097 TI - Prevalence of meningococcal carriage in children and adolescents aged 10-19 years in Chile in 2013. AB - In 2011, Chile experienced an increase in the number of cases of IMD caused by Neisseria meningitidis group W. This epidemiological scenario prompted authorities to implement prevention strategies. As part of these strategies, the Institute of Public Heath of Chile conducted a cross-sectional study to determine the prevalence of pharyngeal carriage of N. meningitidis in a representative sample of healthy children and adolescents aged 10-19 years. The identification of presumptive N. meningitidis strains was performed by testing carbohydrate utilization in the National Reference Laboratory at the ISP. Association of meningococcal carriage with risk factors was analyzed by calculating the Odds Ratio. Selected variables were included in a logistic model for risk analyses. The prevalence of carriage of N. meningitidis was 6.5% (CI: 5.7-7.3%). Older age (carriers: 14.2+/-0.29 vs. non-carriers: 13.8+/-0.08 years old; p=0.009), cohabitation with children (carriers: 0.9+/-0.13 vs. non-carriers: 0.7+/-0.03; p=0.028), number of smoking cohabitants (carriers: 0.55+/-0.13 vs. non-carriers: 0.44+/-0.03) and frequent attendance to crowded social venues (carriers: 49% vs. non-carriers: 37%; p=0.008) were determined to favor carriage. Statistical modeling showed that meningococcal carriage was associated with older age (OR: 1.077, p-value: 0.002) and cohabitation with children (OR: 1.182, p-value: 0.02). PMID- 26819098 TI - Response to: 'A relationship between extracapsular involvement and response to steroid treatment in polymyalgia rheumatica: too soon to conclude?' by Yang et al. PMID- 26819099 TI - Anti-TNFalpha agents curb platelet activation in patients with rheumatoid arthritis. AB - BACKGROUND: Cardiovascular disease is important in rheumatoid arthritis (RA). Tissue factor (TF) is expressed upon platelet activation and initiates coagulation. Anti-tumour necrosis factor-alpha (TNFalpha) agents seem to decrease RA-associated cardiovascular events. We investigated whether (1) TNFalpha activates human platelets and (2) TNFalpha pharmacological blockade modulates the platelet-leucocyte reciprocal activation in RA. DESIGN: The expression of platelet TNFalpha receptors has been assessed by flow cytometry and immunogold electron microscopy. Platelet and leucocyte activation has been assessed also in the presence of antibodies against the TNFalpha receptors 1 and 2 and of infliximab. TF expression, binding to fibrinogen and phosphatidylserine exposure, has been assessed by flow cytometry, TF activity by coagulation time and by endogenous thrombin generation. Markers of platelet and leucocyte activation have been assessed in 161 subjects: 42 patients with RA, 12 with osteoarthritis, 37 age-matched and sex-matched patients with chronic stable angina and 70 age matched and sex-matched healthy subjects. RESULTS: TNFalpha elicited the platelet activation and the expression of TF, which in turn prompted thrombin generation and clot formation. Inhibition of the TNFalpha-induced activation restricted platelet ability to activate leucocytes and to induce leucocyte TF. TNFalpha inhibition did not influence platelet activation induced by collagen, ADP or thrombin receptor activating peptide-6. Platelets of patients with RA were more activated than those of controls. Activation was reduced in patients treated with TNFalpha inhibitors. CONCLUSIONS: TNFalpha-dependent pathways control platelet activation and TF expression in RA. Further studies will verify whether the protective effect of TNFalpha inhibitors on cardiovascular events involves their ability to modulate platelet function. PMID- 26819100 TI - A unique self-organization of bacterial sub-communities creates iridescence in Cellulophaga lytica colony biofilms. AB - Iridescent color appearances are widespread in nature. They arise from the interaction of light with micron- and submicron-sized physical structures spatially arranged with periodic geometry and are usually associated with bright angle-dependent hues. Iridescence has been reported for many animals and marine organisms. However, iridescence has not been well studied in bacteria. Recently, we reported a brilliant "pointillistic" iridescence in colony biofilms of marine Flavobacteria that exhibit gliding motility. The mechanism of their iridescence is unknown. Here, using a multi-disciplinary approach, we show that the cause of iridescence is a unique periodicity of the cell population in the colony biofilm. Cells are arranged together to form hexagonal photonic crystals. Our model highlights a novel pattern of self-organization in a bacterial biofilm. "Pointillistic" bacterial iridescence can be considered a new light-dependent phenomenon for the field of microbiology. PMID- 26819101 TI - DNAism: exploring genomic datasets on the web with Horizon Charts. AB - BACKGROUND: Computational biologists daily face the need to explore massive amounts of genomic data. New visualization techniques can help researchers navigate and understand these big data. Horizon Charts are a relatively new visualization method that, under the right circumstances, maximizes data density without losing graphical perception. RESULTS: Horizon Charts have been successfully applied to understand multi-metric time series data. We have adapted an existing JavaScript library (Cubism) that implements Horizon Charts for the time series domain so that it works effectively with genomic datasets. We call this new library DNAism. CONCLUSIONS: Horizon Charts can be an effective visual tool to explore complex and large genomic datasets. Researchers can use our library to leverage these techniques to extract additional insights from their own datasets. PMID- 26819102 TI - Long-term evaluation of the effect of hypofractionated high-energy proton treatment of benign meningiomas by means of (11)C-L-methionine positron emission tomography. AB - PURPOSE: To determine if (11)C-L-methionine PET is a useful tool in the evaluation of the long-term effect of proton beam treatment in patients with meningioma remnant. METHODS: Included in the study were 19 patients (4 men, 15 women) with intracranial meningioma remnants who received hypofractionated high energy proton beam treatment. Patients were examined with (11)C-L-methionine PET and MRI prior to treatment and after 6 months, and 1, 2, 3, 5, 7 and 10 years. Temporal changes in methionine uptake ratio, meningioma volume, meningioma regrowth and clinical symptoms throughout the follow-up period were evaluated. RESULTS: In 17 patients the tumour volume was unchanged throughout the follow-up. The methionine uptake ratio on PET decreased over the years in most patients. In two patients the tumour remnant showed progression on MRI. In these patients, prior to the volume increase on MRI, the methionine uptake ratio increased. One patient experienced transient clinical symptoms and showed radiological evidence of a radiation-induced reaction close to the irradiated field. CONCLUSION: Proton beam treatment is a safe and effective treatment for achieving long-term growth arrest in meningioma remnants. Follow-up with (11)C-L-methionine PET may be a valuable adjunct to, but not a replacement for, standard radiological follow-up. PMID- 26819103 TI - Evaluation of (68)Ga-DOTA-TOC PET/CT for the detection of duodenopancreatic neuroendocrine tumors in patients with MEN1. AB - CONTEXT: Somatostatin receptor scintigraphy with (111)In-pentetreotide (SRS) is used to detect duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). However, SRS has limited sensitivity for this purpose. Positron emission tomography/computed tomography (PET/CT) with (68)Ga DOTA-TOC has a higher rate of sporadic dpNETs detection than SRS but there is little data for dpNETs detection in MEN1. PURPOSE: To compare the performances of (68)Ga-DOTA-TOC PET/CT, SRS and contrast-enhanced computed tomography (CE-CT) to diagnose dpNETs in MEN1. DESIGN AND SETTING: Single-institution prospective comparative study PATIENTS AND METHODS: Nineteen consecutive MEN1 patients (aged 47 +/- 13 years) underwent (68)Ga-DOTA-TOC PET/CT, SRS, and CE-CT within 2 months in random order. Blinded readings of images were performed separately by experienced physicians. Unblinded analysis of CE-CT, combined with additional magnetic resonance imaging, endoscopic-ultrasound, (18)F-2-fluoro-deoxy-D-glucose ((18)F-FDG) PET/CT or histopathology results served as reference standard for dpNETs diagnosis. RESULTS: The sensitivity of (68)Ga-DOTA-TOC PET/CT, SRS, and CE CT was 76, 20, and 60 %, respectively (p < 0.0001). All the true-positive lesions detected by SRS were also depicted on (68)Ga-DOTA-TOC PET/CT. (68)Ga-DOTA-TOC PET/CT detected lesions of smaller size than SRS (10.7 +/- 7.6 and 15.2 +/- 5.9 mm, respectively, p < 0.03). False negatives of (68)Ga-DOTA-TOC PET/CT included small dpNETs (<10 mm) and (18)F-FDG PET/CT positive aggressive dpNETs. No false positives were recorded. In addition, whole-body mapping with (68)Ga-DOTA-TOC PET/CT identified extra-abdominal MEN1-related tumors including one neuroendocrine thymic carcinoma identified by the three imaging procedures, one bronchial carcinoid undetected by CE-CT and three meningiomas undetected by SRS. CONCLUSIONS: Owing to higher diagnostic performance, (68)Ga-DOTA-TOC PET/CT (or alternative (68)Ga-labeled somatostatin analogues) should replace (111)In pentetreotide in the investigation of MEN1 patients. PMID- 26819105 TI - [Not Available]. PMID- 26819104 TI - Early nasogastric tube feeding in optimising treatment for hyperemesis gravidarum: the MOTHER randomised controlled trial (Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding). AB - BACKGROUND: Hyperemesis gravidarum (HG), or intractable vomiting during pregnancy, is the single most frequent cause of hospital admission in early pregnancy. HG has a major impact on maternal quality of life and has repeatedly been associated with poor pregnancy outcome such as low birth weight. Currently, women with HG are admitted to hospital for intravenous fluid replacement, without receiving specific nutritional attention. Nasogastric tube feeding is sometimes used as last resort treatment. At present no randomised trials on dietary or rehydration interventions have been performed. Small observational studies indicate that enteral tube feeding may have the ability to effectively treat dehydration and malnutrition and alleviate nausea and vomiting symptoms. We aim to evaluate the effectiveness of early enteral tube feeding in addition to standard care on nausea and vomiting symptoms and pregnancy outcomes in HG patients. METHODS/DESIGN: The MOTHER trial is a multicentre open label randomised controlled trial ( www.studies-obsgyn.nl/mother ). Women >= 18 years hospitalised for HG between 5 + 0 and 19 + 6 weeks gestation are eligible for participation. After informed consent participants are randomly allocated to standard care with intravenous rehydration or early enteral tube feeding in addition to standard care. All women keep a weekly diary to record symptoms and dietary intake until 20 weeks gestation. The primary outcome will be neonatal birth weight. Secondary outcomes will be the 24-h Pregnancy Unique Quantification of Emesis and nausea score (PUQE-24), maternal weight gain, dietary intake, duration of hospital stay, number of readmissions, quality of life and side-effects. Also gestational age at birth, placental weight, umbilical cord plasma lipid concentration and neonatal morbidity will be evaluated. Analysis will be according to the intention to treat principle. DISCUSSION: With this trial we aim to clarify whether early enteral tube feeding is more effective in treating HG than intravenous rehydration alone and improves pregnancy outcome. TRIAL REGISTRATION: TRIAL REGISTRATION NUMBER: NTR4197 . Date of registration: October 2(nd) 2013. PMID- 26819106 TI - Palmoplantar keratodermas: clinical and genetic aspects. AB - Palmoplantar keratodermas comprise a diverse group of acquired and hereditary disorders marked by excessive thickening of the epidermis of palms and soles. Early onset and positive family history suggest a genetic cause. While hereditary forms of palmoplantar keratoderma (PPK) may represent the sole or dominant clinical feature, they may also be associated with other ectodermal defects or extracutaneous manifestations. In recent years, much progress has been made in deciphering the genetic basis of PPK, which has led to the emergence of new disorders and syndromes. The elucidation of disease mechanisms has opened new avenues for specific therapies, increasingly sparking interest in this field. Given the high heterogeneity with respect to clinical features, genetic defects, and disease mechanisms, the classification of PPK is based on various criteria. These include extent of disease manifestations, morphology of palmoplantar skin involvement, inheritance patterns, and molecular pathogenesis. Though not always feasible, the clinical distinction of various PPK entities is based on fine-tuned criteria or clues. Remarkably, apparently distinct disorders have been shown to be allelic, as they are caused by mutations in the same gene. By contrast, similar clinical pictures may result from mutations in different genes. Because of this complexity, mutation analysis is required to determine the precise type of PPK. The best-defined entities are described in this review. PMID- 26819109 TI - The use of dermatoscopy in diagnosis and therapy of nonmelanocytic skin cancer. AB - Today, dermatoscopy is an integral part of every clinical skin examination, as it markedly enhances the early detection of melanocytic and nonmelanocytic skin cancer (NMSC) compared to naked-eye inspection. Besides its diagnostic use, this noninvasive method is increasingly important in the selection of as well as the response assessment to various therapies used for NMSC, including basal cell carcinoma, actinic keratoses, squamous cell carcinoma, and also rare tumors such as Merkel cell carcinoma, angiosarcoma, or dermatofibrosarcoma protuberans. Thus, dermatoscopy is a valid tool for the preoperative assessment of tumor margins in basal cell carcinoma, but also for follow-up of actinic keratoses after topical treatment. The present article presents an overview on the use of dermatoscopy in the diagnosis and therapy of various types of NMSC. PMID- 26819111 TI - Biomarker value and pitfalls of serum S100B in the follow-up of high-risk melanoma patients. AB - BACKGROUND AND OBJECTIVES: Serum levels of S100B are standard in monitoring advanced malignant melanoma patients in order to discriminate progressive from non-progressive disease. False-positive results lead to distress among patients and increase the amount of cost-intensive diagnostics. We therefore analyzed reported comorbid diseases as putative sources of excessive S100B release. PATIENTS AND METHODS: Here, we report a single-center experience on serum S100B levels in 2,664 blood samples from 1,113 stage IB to IV melanoma patients (AJCC) who presented for follow-up examinations over a period of 24 months. RESULTS: Overall, 295 (11%) of patients developed disease progression. In patients with a high tumor load, the rate of false-negative results was 30/185 (16%). The rate of false-positive results was 247/2369 (12%). One hundred and six false-positive results (69%) compared to 46 true-positive results (31%) were found in patients with cardiovascular diseases such as arrhythmia (50/32) or previous myocardial infarction (22/14). Moreover, obesity (85/14), liver cirrhosis (31/10), migraine (18/2), chronic kidney disease (13/2), and previous stroke (11/1) were found to be associated with false-positive S100B levels. CONCLUSIONS: Serum S100B is a useful quantitative biomarker in routine follow-up of high-risk melanoma patients. While false-negative results are frequent in patients with low tumor load, false-positive results are associated with several comorbid diseases and warrant careful reevaluation. PMID- 26819115 TI - Basal cell carcinomas with perineural invasion: a clinical-therapeutic and histological challange. PMID- 26819113 TI - Trauma-induced pemphigus: a case series of 36 patients. AB - BACKGROUND AND OBJECTIVES: Pemphigus is a group of autoimmune diseases characterized by intraepidermal acantholytic blisters. Isomorphic responses, or Koebner phenomenon (KP), defined as the appearance of typical lesions of a disease following trauma are rarely reported in pemphigus. Our aim was to present patients who developed new pemphigus lesions as a result of skin trauma. PATIENTS AND METHODS: The medical files of pemphigus patients from the Autoimmune Bullous Diseases Research Center, who had a history of trauma before the onset or flare of their disease, between 1999 and 2013 were reviewed. RESULTS: Thirty-six pemphigus vulgaris (PV) patients had a history of trauma. Thirteen patients developed new-onset PV and the other 23 had previously been diagnosed with PV. Pemphigus lesions developed most often following major surgeries including abdominal, orthopedic, and chest surgeries as well as dental procedures, blunt physical trauma, and skin surgeries. Moreover, post-cataract laser surgery, burns, radiation therapy, and physiotherapy were also shown to induce pemphigus. Mean time between trauma and lesions was 4.7 weeks for recurrent PV and 15.0 weeks for new-onset PV. CONCLUSIONS: Unnecessary surgery and blunt trauma should be avoided in pemphigus patients. Furthermore, posttraumatic pemphigus should be suspected in poorly healing surgical wounds and confirmatory biopsies are mandatory. PMID- 26819116 TI - Human bites - the gap in our dermatology textbooks. PMID- 26819124 TI - German guidelines for the diagnosis and therapy of localized scleroderma. AB - Localized scleroderma designates a heterogeneous group of sclerotic skin disorders. Depending on the subtype, severity, and site affected, adjacent structures such as adipose tissue, muscles, joints, and bones may be involved. This is an update of the existing German AWMF (Association of the Scientific Medical Societies in Germany) guidelines (classification: S2k). These guidelines provide an overview of the definition, epidemiology, classification, pathogenesis, laboratory workup, histopathology, clinical scoring systems, as well as imaging and device-based workup of localized scleroderma. Moreover, consensus-based recommendations are given on the management of localized scleroderma depending on its clinical subtype. Treatment recommendations are presented in a therapeutic algorithm. No financial support was given by any pharmaceutical company. The guidelines are valid until July 2019. PMID- 26819128 TI - [Not Available]. PMID- 26819130 TI - [Not Available]. PMID- 26819133 TI - Abnormalities of Fetal Situs: An Overview and Literature Review. AB - The incidence of congenital heart disease is most commonly reported in 8 per 1000 live births. Situs anomalies are among the least common forms of congenital heart disease. This study defines situs and describes the variations of fetal situs anomalies. Situs refers to the arrangement of the viscera, atria, and vessels within the body. Situs solitus describes the normal arrangement; situs inversus describes inverted arrangement of the viscera and atria; and situs ambiguous (also referred to as heterotaxy) describes disturbances in arrangements that can neither be identified as solitus nor inversus. This review will concentrate on heterotaxy, as it is the most complicated situs abnormality to define, classify, and study. Prognosis of heterotaxy is variable but most correlated with cardiac anatomy. Management is concentrated on numerous cardiac operations and requires a multidisciplinary approach to address coexisting congenital anomalies. PMID- 26819134 TI - Delayed Cord Clamping in Preterm Neonates: A Review of Benefits and Risks. AB - IMPORTANCE: Delayed clamping of the umbilical cord of premature neonates decreases perinatal morbidity. Allowing time for autotransfusion of placental blood before the umbilical cord is clamped represents a simple practice that may have significant impact. In light of many professional societies recommending delayed cord clamping in premature neonates because of its beneficial effects, the topic still holds many unanswered questions. OBJECTIVE: The purpose of this article is to review the most recent evidence available regarding delayed cord clamping in premature neonates. EVIDENCE ACQUISITION: A literature search using PubMed, Cochrane database, and cumulative index of nursing and allied health literature provided the references for this review. RESULTS: Although the evidence comes primarily from small trials, delayed umbilical cord clamping in premature neonates is associated with less need for red blood cell transfusions, increase in hemoglobin and hematocrit levels, and decrease in risk of intraventricular hemorrhage and necrotizing enterocolitis. No maternal or neonatal risks have been demonstrated. Data on long-term outcomes are lacking. CONCLUSIONS AND RELEVANCE: Delayed cord clamping in premature neonates is a simple procedure that the current evidence supports to improve neonatal morbidity. The impact on long-term outcomes remains limited. The optimal time to delay cord clamping and potential risks are poorly studied. PMID- 26819135 TI - Changes in the Practice of Obstetrics and Gynecology. AB - A projected shortage of obstetrician-gynecologists (OB-GYNs) is a result of both the increasing US population and the relatively static number of residency graduates. In addition, generational changes have contributed to increasing subspecialization, more desiring part-time employment, and earlier retirement. This article reviews data regarding changes in the practice of obstetrics and gynecology. Residency education is focusing more on a core curriculum in general obstetrics and gynecology, while subspecialty fellowship training has grown in popularity. There are no recent data to describe whether OB-GYNs are working fewer hours, yet more are employed in larger practices at mostly metropolitan locations. A team-based care model that incorporates nonphysician clinicians and digital conversion of clinical data has been encouraged to increase accessibility, improve comprehensiveness, commit to more continuity of care, and reduce redundancy. Compared with other medical specialists, OB-GYNs retire slightly earlier, especially females who will represent the field more. The specialty is moving toward a more comprehensive women's health care practice model that is more patient-centered, efficient, cost controlling, team-based, and adaptable to the needs of a diverse population. Implications from these changes for our practices and improving patient care are currently unclear and await more reported experience. PMID- 26819136 TI - Self-Association of Apo A-1 Studied with Dynamic and Static Light Scattering. AB - Static and dynamic light scattering were employed to determine simultaneously the average relative molecular mass, Mr, and the average hydrodynamic radius, Rh, of protein molecules. The new method was applied to the association-dissociation equilibrium of apolipoprotein A-1 (Apo A-1) and its thermal unfolding. As a control, lysozyme was measured as a nonassociating protein. Apo A-1 forms oligomers as a function of concentration and temperature, and the equilibrium can be described by a cooperative association model, consisting of a nucleation step and a growth step. At concentrations of 1 and 2.7 mg/mL, the Apo A-1 solution contained mainly monomers and octamers, with intermediates occurring at very low concentrations. Oligomer formation was maximal at 22 degrees C and was characterized by a temperature-dependent association constant. The cooperative association model allows the quantitative analysis of both the average relative molecular mass, Mr, and the average hydrodynamic radius, Rh, with the same set of model parameters which, in turn, are also applicable to analytical ultracentrifugation experiments. The light scattering experiments were reversible as long as the Apo A-1 solution was not heated above 60 degrees C. PMID- 26819137 TI - Sex disparities in systemic sclerosis-associated pulmonary arterial hypertension: a cohort study. AB - BACKGROUND: The impact of male sex as a determinant of health outcomes in systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is controversial. The primary objective of this study was to evaluate the effect of sex on survival in patients with SSc-PAH. The secondary objectives were to evaluate the effect of sex on age of PAH diagnosis, time from SSc diagnosis to PAH diagnosis, and SSc disease manifestations. METHODS: Sex-based disparities were evaluated in a cohort of SSc-PAH patients with a primary outcome of time from PAH diagnosis to all-cause mortality. Secondary outcomes were differences in age of diagnosis, disease duration, and SSc manifestations. Survival differences were evaluated using Kaplan-Meier and Cox proportional hazard models. RESULTS: We identified 378 SSc-PAH (58 males, 320 females) patients, with a female:male ratio of 5.5:1. Males had a shorter mean +/- standard deviation time from SSc diagnosis to PAH diagnosis (1.7 +/- 14 versus 5.5 +/- 14.2 years); shorter PAH duration (3.5 +/- 3.1 versus 4.7 +/- 4.2 years), increased frequency of renal crisis (19 % versus 8 %, relative risk (RR) 2.33, 95 %CI 1.22, 4.46), interstitial lung disease (67 % versus 48 %, RR 1.41, 95 %CI 1.14, 1.74), and diffuse subtype (40 % versus 22 %, RR 1.84, 95 %CI 1.26, 2.69). Males appeared to have decreased 1-, 2 , 3-, and 5-year survival (83.2 %, 68.7 %, 53.2 %, 45.6 %) compared to females (85.7 %, 75.7 %, 66.4 %, 57.4 %). However, there was no difference in mortality between sexes (HR 1.43 (95 %CI 0.97, 2.13). CONCLUSIONS: Sex disparities appear to exist in the frequency of PAH, time to PAH diagnosis, PAH disease duration and SSc disease burden. However, male sex does not independently impact SSc-PAH survival. PMID- 26819138 TI - Does chemotherapy improve health-related quality of life in advanced pancreatic cancer? A systematic review. AB - Chemotherapy is increasingly being used in advanced pancreatic cancer, but side effects are common. The aim of this systematic review was to assess whether chemotherapy improves health-related quality of life (HRQoL), pain or cachexia. Thirty studies were reviewed. Four of 23 studies evaluating HRQoL, 7 of 24 studies evaluating pain and 0 of 8 studies evaluating cachexia found differences between treatment arms. Change in HRQoL from baseline was evaluated in 14 studies: five studies reported an improvement in at least one treatment arm; three a worsening and the remaining stable scores. Change in pain intensity from baseline was evaluated in eight studies, and improvement was observed in seven. Of the four studies reporting improved survival, three reported improved HRQoL or pain. In conclusion, chemotherapy can stabilize HRQoL and improve pain control. Effects on cachexia are hard to elucidate. Improved survival does not come at the expense of HRQoL or pain control. PMID- 26819139 TI - RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations. AB - BACKGROUND: Avian infectious bronchitis is a highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high (L10H line) and low (L10L line) serum concentration of mannose binding lectin (MBL) were studied. In total, 32 birds from each line were used. Sixteen birds from each line were infected with IBV and sixteen were left uninfected. Eight uninfected and infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds and differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and in the same way for infected birds. Functional analysis was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. RESULTS: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were "Lymphocyte activation involved in immune response" and "Somatic recombination of immunoglobulin genes involved in immune response" at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were "Alpha-beta T cell activation" and "Positive regulation of leukocyte activation" at weeks 1 and 3, respectively. CONCLUSIONS: Healthy birds from the two lines showed significant differences in expression profiles for subsets of adaptive and innate immunity-related genes, whereas comparison of the IBV infected birds from the two lines showed differences in expression of immunity related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had influenced innate as well as adaptive immunity. PMID- 26819141 TI - The contribution of locational factors to regional variations in office-based physicians in Germany. AB - There is considerable literature showing that regional variation in the number of office-based physicians is rather explained by factors such as financial attractiveness of a region or employment opportunities for spouses than by health care needs of the population. It remains unclear, however, how much of the variation is explained by each of these determinants. The aim of the present study is to estimate the percentage contribution of a variety of determinants to the measured variation in Germany. Physician density is regressed on a well defined set of explanatory variables that were identified as determinants of physician location. Regression-based decomposition was applied to decompose the variation in physician density into the percentage contribution of each of the determinants. The results show that varying health care needs of the population explained less than 5.2% of the variation in physician density. Percentage of population with private health insurance explained 14% of the variation in GP density and between 2% and 6% of the variation in specialists' density. For specialists, a higher share of variance was attributable to the variables measuring sociocultural amenities of a region compared to GPs. PMID- 26819140 TI - The efficiency of health care production in OECD countries: A systematic review and meta-analysis of cross-country comparisons. AB - There has been an ongoing interest in the analysis and comparison of the efficiency of health care systems using nonparametric and parametric applications. The objective of this study was to review the current state of the literature and to synthesize the findings on health system efficiency in OECD countries. We systematically searched five electronic databases through August 2014 and identified 22 studies that analyzed the efficiency of health care production at the country level. We summarized these studies with view on their sample, methods, and utilized variables. We developed and applied a checklist of 14 items to assess the quality of the reviewed studies along four dimensions: reporting, external validity, bias, and power. Moreover, to examine the internal validity of findings we meta-analyzed the efficiency estimates reported in 35 models from ten studies. The qualitative synthesis of the literature indicated large differences in study designs and methods. The meta-analysis revealed low correlations between country rankings suggesting a lack of internal validity of the efficiency estimates. In conclusion, methodological problems of existing cross-country comparisons of the efficiency of health care systems draw into question the ability of these comparisons to provide meaningful guidance to policy-makers. PMID- 26819142 TI - Expanding choice of primary care in Finland: much debate but little change so far. AB - "Putting the patient in the driver's seat" is one of the top issues on the health policy agenda in Finland. One of the means believed to promote patient empowerment and patient centeredness is the introduction and further expansion of choice policies with accompanying competition between public and private service providers. However, the Finnish health care system has a highly decentralized administration with multiple funding sources and three different types of providers that people can seek primary care from (municipal health centers, occupational health care services, and private sector providers). This complicates the implementation of choice at the level of primary health care. In this paper, we describe the current policy debates and initiatives promoting the expansion of the choice of primary care provider in Finland. We examine the legislation and policies that have contributed to the current, complex service system in Finland. In light of this examination, we critically discuss the current debate on choice policies as well as the introduction of choice in the context of primary health care. PMID- 26819143 TI - Synucleinopathies: past, present and future. PMID- 26819144 TI - Use of statins and reduced risk of recurrence of VTE in an older population. A population-based cohort study. AB - We aimed to determine whether statin use is associated with a decreased risk of recurrent venous thromboembolism (VTE) in older patients. We used a pre-assembled cohort of patients at least 65 years of age diagnosed with incident VTE between January 1, 1994 and December 31, 2004 in the province of Quebec, Canada and followed until December 31, 2005. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) of recurrent VTE associated with current and past use of statins, compared with non-use. The cohort included 25,681 patients with incident VTE. During a mean follow-up of 3.0 years, there were 2343 recurrent VTE events (rate: 3.1 per 100 person-years). Compared with non-use, current use of statins was associated with a decreased risk of VTE recurrence (rates: 1.55 vs 3.47 per 100 per year, respectively; HR: 0.74, 95 % CI: 0.61-0.89), while no association was observed with past use (HR: 0.98, 95 % CI: 0.76-1.25). In a secondary analysis, longer durations of statin use were associated with greater risk reductions (0-6 months, HR 0.82, 95 % CI: 0.67-1.01; 6-12 months, HR 0.62, 95 % CI: 0.43-0.90; >= 12 months, HR: 0.50, 95 % CI: 0.33-0.74; p-value for trend <= 0.001). The use of statin was associated with a decreased risk of recurrent VTE in older patients. This study supports the need for randomised controlled trials to assess the efficacy and safety of statins in the long-term treatment of VTE. PMID- 26819145 TI - Improved anaerobic digestion of a thermally pretreated mixture of physicochemical sludge; broiler excreta and sugar cane wastes (SCW): Effect on organic matter solubilization, biodegradability and bioenergy production. AB - Thermal pretreatment effect of a mixture of organic wastes (physicochemical sludge, excreta of broiler chickens and sugarcane wastes (SCW)) in the solubilization and biodegradability organic matter as well as bioenergy production by anaerobic digestion was evaluated. Two different mixtures of physicochemical sludge, excreta of broiler chickens and SCW (70%, 15%, 15% and 60%, 20%, 20% of VS, respectively) were treated at different temperatures (80 degrees C, 85 degrees C and 90 degrees C) and contact time (30, 60 and 90 min). Results indicate that, organic matter solubilization degree increased from 1.14 to 6.56%; subsequently, in the anaerobic digestion process, an increase of 50% in the volatile solids removal and 10% in biogas production was observed, while, retention time decreased from 23 up to 9 days. The results obtained were similar to pilot-scale. In both experimental scales it showed that the synergy produced by the simultaneous anaerobic digestion of different substrates could increase bioenergy production up to 1.3 L bio g(-1) VS removed and 0.82 L CH4 g(-1) VS removed. The treatment conditions presented in this study allow for large residue quantities to be treated and large bioenergy quantities to be produced (10% higher than during conventional treatment) without increasing the anaerobic digester volume. PMID- 26819146 TI - Access to water provides economic relief through enhanced relationships in Kenya. AB - Introduction: Sub-Saharan Africa is comprised of low- and middle-income countries subject to the residual effects of chronic poverty. Poverty contributes to health disparities and social inequities. Public health strategies and solutions seek to remedy the effects of poverty. Providing access to quality water is one priority public health project that alleviates adverse health effects, but may have additional outcomes. Previous research has not thoroughly reviewed the economic relief and relationship changes from implemented water interventions. Methods: A qualitative phenomenological approach used 52 semi-structured interviews to understand relationship experiences among primary water gatherers and their families after implemented water interventions in a community. This study took place throughout the historically semi-arid eastern region in Kitui, Kenya, where community members have been beneficiaries of various water interventions. Results: Prior to the water intervention, relationships were strained because of economic hardships. Households experienced economic difficulties in paying for children's school fees, buying bricks for housing structures, having water for house gardens, trees for shade in the compound, crops and providing water for their animals. After receiving access to water, relationships improved, because families were able to discuss and address economic challenges. Additional financial revenue was gained and used to pay for water to make bricks to sell or use on housing structures, expand on house gardens and agricultural crops, build new businesses, purchase water for animals, and construct local water spouts near the household. Discussion: Access to water improved relationships, which encouraged economic growth. This information provides a critical component in understanding the interconnected nature between access to water, poverty and family relationships. Ultimately, this research suggests an increased need for access to quality water worldwide to improve both economic situations and relationships in low- and middle-income countries. PMID- 26819147 TI - Measuring the impact of Health Trainers Services on health and health inequalities: does the service's data collection and reporting system provide reliable information? AB - Background: The Health Trainers Service is one of the few public health policies where a bespoke database-the Data Collection and Reporting System (DCRS)-was developed to monitor performance. We seek to understand the context within which local services and staff have used the DCRS and to consider how this might influence interpretation of collected data. Methods: In-depth case studies of six local services purposively sampled to represent the range of service provider arrangements, including detailed interviews with key stakeholders (n = 118). Results: Capturing detailed information on activity with clients was alien to many health trainers' work practices. This related to technical challenges, but it also ran counter to beliefs as to how a 'lay' service would operate. Interviewees noted the inadequacy of the dataset to capture all client impacts; that is, it did not enable them to input information about issues a client living in a deprived neighbourhood might experience and seek help to address. Conclusions: The utility of the DCRS may be compromised both by incomplete ascertainment of activity and by incorrect data inputted by some Health Trainers. The DCRS is also underestimate the effectiveness of work health trainers have undertaken to address 'upstream' factors affecting client health. PMID- 26819148 TI - A family-based model for Iranian women's health: a grounded theory study. AB - Background: In many societies, women are vulnerable to specific situations and inequalities, which may negatively impact their own and their family's health. The purpose of this qualitative study was to explore Iranian women's perspectives on this issue and to develop a categorical model for their health. Methods: The study was conducted using a grounded theory approach via 25 semi-structured interviews. Results: The results revealed that family dynamism was the core variable and identified four main categories: understanding of health, reduction of women's health, the pleasure and difficulties of motherhood, cultural and/or social factors influencing women's health. Conclusion: Policymakers should consider policies that empower women, reduce gender inequality and provide social security to maximize the probability of women being healthy. PMID- 26819150 TI - Minimally invasive treatment of rectovesical fistula: A case report. AB - Management of rectovesical fistulas poses a significant challenge where a definitive surgical treatment is necessary in the majority of the patients. The application of transanal endoscopic surgery is an useful option, adding the adventages of a minimally invasive surgery. We report our first case of transanal endoscopic surgical treatment of RVF with a successful outcome. PMID- 26819151 TI - Prevalence and predictors of complications following facial reconstruction procedures. AB - Facial reconstruction procedures are immensely challenging and are done for a multitude of reasons. The purpose of this report is to provide nationally representative estimates of different types of facial reconstructive procedures and to examine prevalence and predictors of a wide range of complications associated with these procedures in the USA. The Nationwide Inpatient Sample, the largest inpatient dataset for the USA, was used. Data for the years 2004-2010 related to facial reconstruction procedures were identified through ICD-9-CM procedure codes. Associated complications were identified using secondary diagnosis field codes. Multivariable logistic regression models were used to examine the association between patient/hospital-level factors and the occurrence of complications. A total 26,374 facial reconstruction procedures were performed. About 20% of all patients who had facial reconstruction procedures developed a complication. Frequently occurring complications included postoperative pneumonia (4.9% of hospitalizations), hemorrhage (3.9%), other infections (3.6%), non healing wounds (3.5%), and iatrogenically induced complications (3.2%). Significant factors found to be consistently associated with different types of complications included age, co-morbid burden, sex, and type of admission. The reported results are generalizable within limitations and can be used by health care providers to tailor quality improvement initiatives to minimize or better treat complications in the high-risk cohorts. PMID- 26819152 TI - Children in emergency situation - a red alert for Pakistan. PMID- 26819149 TI - Reduction in parvalbumin expression not loss of the parvalbumin-expressing GABA interneuron subpopulation in genetic parvalbumin and shank mouse models of autism. AB - BACKGROUND: A reduction of the number of parvalbumin (PV)-immunoreactive (PV(+)) GABAergic interneurons or a decrease in PV immunoreactivity was reported in several mouse models of autism spectrum disorders (ASD). This includes Shank mutant mice, with SHANK being one of the most important gene families mutated in human ASD. Similar findings were obtained in heterozygous (PV+/-) mice for the Pvalb gene, which display a robust ASD-like phenotype. Here, we addressed the question whether the observed reduction in PV immunoreactivity was the result of a decrease in PV expression levels and/or loss of the PV-expressing GABA interneuron subpopulation hereafter called "Pvalb neurons". The two alternatives have important implications as they likely result in opposing effects on the excitation/inhibition balance, with decreased PV expression resulting in enhanced inhibition, but loss of the Pvalb neuron subpopulation in reduced inhibition. METHODS: Stereology was used to determine the number of Pvalb neurons in ASD associated brain regions including the medial prefrontal cortex, somatosensory cortex and striatum of PV-/-, PV+/-, Shank1-/- and Shank3B-/- mice. As a second marker for the identification of Pvalb neurons, we used Vicia Villosa Agglutinin (VVA), a lectin recognizing the specific extracellular matrix enwrapping Pvalb neurons. PV protein and Pvalb mRNA levels were determined quantitatively by Western blot analyses and qRT-PCR, respectively. RESULTS: Our analyses of total cell numbers in different brain regions indicated that the observed "reduction of PV(+) neurons" was in all cases, i.e., in PV+/-, Shank1-/- and Shank3B-/- mice, due to a reduction in Pvalb mRNA and PV protein, without any indication of neuronal cell decrease/loss of Pvalb neurons evidenced by the unaltered numbers of VVA(+) neurons. CONCLUSIONS: Our findings suggest that the PV system might represent a convergent downstream endpoint for some forms of ASD, with the excitation/inhibition balance shifted towards enhanced inhibition due to the down regulation of PV being a promising target for future pharmacological interventions. Testing whether approaches aimed at restoring normal PV protein expression levels and/or Pvalb neuron function might reverse ASD-relevant phenotypes in mice appears therefore warranted and may pave the way for novel therapeutic treatment strategies. PMID- 26819153 TI - Issues affecting health professionals during and after catastrophic earthquakes in Van-Turkey. AB - OBJECTIVE: To assess physical and psycho-social problems faced by health professionals, and to analyse the ethical, legal and triage dimensions of disaster medical services. METHODS: The descriptive study was conducted from November 2011 to March 2012 and comprised health professionals from two hospitals of Van, Turkey A specific questionnaire was designed and interviews were conducted face to face. SPSS 13 was used for statistical analysis. RESULTS: Of the 430 health professionals who had experienced one or more earthquakes and were part of the study, 225(52.3%) were nurses and 205(47.7%) were doctors. There were 224(52%) women and 206(48%) men. Besides, 206(48) were below 31 years of age. Overall, 193(44.9%) participants experienced chaos, 83(19.3%) panic and fear, and 129(30%) despair. Only 20(4.7%) of them lived at home, while others lived in tents, containers, hospitals or cars during the emergency and continued to provide services despite social, economic and psychological problems. Triage was preferred by 339(78.8%) of the respondents. CONCLUSIONS: Problems of health professionals were multi-dimensional and addressing them would make service delivery more effective. PMID- 26819154 TI - Effects of osteoformin in the rapid distraction osteogenesis of rabbit mandibles. AB - OBJECTIVE: To evaluate the effects of osteoformin on mineralisation and quality of the new bone formation during rapid distraction osteogenesis. METHODS: This multi-centre study was conducted at the Karadeniz Technical University, Middle East Technical University and Selcuk University. The experimental study was conducted from January 2010 to September 2012 and comprised New-Zealand rabbits that were randomly divided into three groups. In group I distraction rate was 1 mm/day while in groups II and III distraction rates were 2mm/day and 1 mm/day. In groups I and II 100ug/kg osteoformin was injected after the latency period. Distraction region was evaluated by radiological, histomorphometrical and dual energy X-ray absorptiometry analyses. SPSS 17 was used for statistical analysis. RESULTS: There were 18 rabbits with each of three groups having 6(33.3%). Accelerated bone healing was noted in groups I and II compared with group III (p<0.05). No significant differences were indicated between groups I and II (p>0.05). CONCLUSIONS: Local injection of osteoformin was effective in the craniomaxillofacial distraction osteogenesis in rabbits. Further experimental studies are recommended before using osteoformin on humans. PMID- 26819155 TI - Effect of HCV on fasting glucose, fasting insulin and peripheral insulin resistance in first 5 years of infection. AB - OBJECTIVE: To assess the effects of hepatitis C virus infection in the first 5 years on fasting glucose, fasting insulin and peripheral insulin resistance. METHODS: The case-control study was conducted at the Army Medical College, Rawalpindi, from December 2011 to November 2012, and comprised subjects recruited from a government hospital in Rawalpindi. The subjects included known cases of hepatitis C virus infection for at least 5 years, and normal healthy controls. Fasting blood samples of all the subjects were collected and analysed for serum fasting insulin and serum fasting glucose levels. Homeostatic model assessment Insulin resistance was calculated SPSS 11 was used for statistical analysis. RESULTS: Of the 30 subjects, 20(66.6%) were cases, while 10(33.3%) were controls. Serum fasting glucose mean level in cases was 89.55+/-9.53 compared to 84.40+/ 9.80 in the controls (p=0.188). The mean serum fasting insulin in controls was 7.52+/-3.23 and 6.79+/-3.30 in cases (p=0.567). Homeostatic model assessment Insulin resistance level in controls was 1.60+/-0.76 and In the cases it was 1.49+/-0.74 (p=0.695). CONCLUSIONS: Peripheral insulin resistance and development of type 2 diabetes as a complication of hepatitis C virus infection was not likely at least within the first five years of infection. PMID- 26819156 TI - Accuracy of intra-operative frozen section in the diagnosis of female genital tract neoplasms. AB - OBJECTIVE: To evaluate the accuracy of intra-operative frozen section in the diagnosis of various pelvic neoplasms, including ovarian tumours. METHODS: The retrospective study was conducted at Shifa International Hospital and comprised records of all patients with lesions of female genital tract who underwent frozen section between January 2010 and December 2012. Comparison was made with the final diagnosis after histopathology was performed on examining permanent paraffin sections. RESULTS: The mean age of the 54 patients was 43.70+/-14.8 years (range: 19-75 years). The frozen section was accurate in 51(92.6%) cases. It had a moderately high sensitivity of 75%, high specificity of 97.6%, high positive predictive value of 90% and high negative predictive value of 93.2%. Lack of agreement was found in cases of ovarian tumours of the mucinous and borderline variety. CONCLUSIONS: Frozen section showed a considerable level of accuracy when dealing with suspected pelvic neoplasms. PMID- 26819157 TI - Biomechanical evaluation of oversized drilling on implant stability - an experimental study in sheep. AB - OBJECTIVE: To evaluate the effect of oversized drilling on implant success and secondary stability. METHODS: The experimental study was conducted in Turkey from January to July 2013, after approval by the ethics committee of the University of Ankara, and comprised 2 female sheep. Alumina blasted implants 4mm in diameter and 10mm in length were employed; 16 implant sites were prepared on the proximal tibias of the 2 sheep. In the right tibia, a standard preparation with 3.5mm diameter was performed in the control group, while in the left tibia, an over preparation with 4.2mm diameter was performed at the experimental group. The implants of the control group were non-mobile, while the experimental group had rotational and vertical movements. The initial implant stability was measured using the resonance frequence analysis. Animals were sacrificed after 12 weeks, and resonance frequence analysis and reverse torque values were measured. RESULTS: In the experimental group, the mean resonance frequence analysis value was 60.25+/-7.46 (range: 49-74) at the end of the 12-week healing period. There was no statistically significant difference between the two groups (p=0.926). In the removing stage, the mean reverse torque values was 97.75+/-22.23N/cm (range: 68.63-138.83) for control group and 96.25+/-21.93N/cm (range: 63.34-126.9) for the experimental group (p=0.84). CONCLUSIONS: Osseointegration can be achieved in the absence of primer stability in the 12-week period of healing time even for alumina-blasted implants. PMID- 26819158 TI - Importance of red blood cell distribution width (RDW) in patients with upper gastrointestinal haemorrhage. AB - OBJECTIVE: To explore the effect of red blood cell distribution width levels on the diagnosis and management of upper gastrointestinal haemorrhage. METHODS: The retrospective study was conducted at Ankara Numune Education and Research Hospital, Turkey, and comprised record of patients diagnosed with upper gastrointestinal haemorrhage from January 1, 2013, to December 31, 2013. Factors analysed were age, gender, red blood cell distribution width level, admission haemoglobin and haematocrit levels, endoscopy findings classified according to the Forrest system, comorbid diseases, use of medications, unhealthy habits like alcohol usage and smoking, and mortality rate. RESULTS: Of the 147 patients, 93(64%) were men. The overall median age of the sample was 60 years. Besides, 117(79.6%) patients had comorbid diseases, of which hypertension 56(38.4%) was the most common. A total of 24(16.8%) patients were using antiplatelet or anticoagulant drugs, while 30(20.5%) were on non-steroidal anti-inflammatory drugs. Peptic ulcer in 128(87.1%) patients was the most common cause of haemorrhage. The median red blood cell distribution width level of the study population was 15.25% which was significantly higher compared to the reference values (p<0.05).. In contrast, haemoglobin 9.55% (3.7) and haematocrit 28.75% (10.8)were significantly lower (p<0.05). Mortality rates were significantly higher in patients with higher red blood cell distribution width values (p<0.05). CONCLUSIONS: Red blood cell distribution width levels were higher during the acute phase of upper gastrointestinal haemorrhage. PMID- 26819159 TI - Squamous cell carcinoma of oral tongue in young patients - A 10 years tertiary care experience. AB - OBJECTIVE: To evaluate the clinical and pathological profile of young patients with squamous cell carcinoma of tongue. METHODS: The retrospective study was conducted at Aga Khan University Hospital, Karachi, and comprised record of patients <35 years presenting with squamous cell carcinoma of tongue between 2001 and 2011. Data was extracted from the electronic database of the hospital for site and age. Clinico-pathological variables were analysed using SPSS 20. RESULTS: Of the 29 patients, 17(58.6%) were men and 12(41.3%) were women. The overall mean age at presentation was 29.6+/-4.4 years. All patients (100%) had some sort of addiction, with 15(51.7%) having more than one addiction. Of the total, 20(68.9%) patients had moderately differentiated carcinoma. At presentation, 20(68.9%) had advanced stage (III-IV) disease. Surgery was the primary modality used in all the patients (100%). Median follow-up period was 36 months (range: 1-6 years). During follow-up, 7(24.1%) patients developed recurrence. CONCLUSIONS: Squamous cell carcinoma of the tongue was more commonly seen in males, and multiple addictions were a common risk factor. PMID- 26819161 TI - Perceptions and attitudes towards research amongst medical students at Shifa College of Medicine. AB - OBJECTIVE: To understand medical students' perceptions and attitudes towards research to help facilitators design specific courses according to their needs. METHODS: The cross-sectional study was conducted at Shifa College of Medicine, Islamabad, Pakistan, from May to November 2013, and comprised undergraduate medical students. A pre-tested questionnaire was used for data collection. Students' response was recorded on a Likert scale from 'strongly disagree' 1 to 'strongly agree' 5. Analysis was done using statistical SPSS17. RESULTS: Of the 195 students enrolled, 172(88%) responded. Overall, 78(45.3%) students said they were aware of research. Research was considered useful for their professional careers and relevant to their daily life by 133(65.7%) students, while 72(41.9%) did not consider it worthwhile to pursue research as a career. Besides, 71(41.3%) students enjoyed research, while 120(70%) perceived research as stressful and 107(62.2) complex. CONCLUSIONS: Most students considered research valuable but at the same time they perceived it as stressful and complex. PMID- 26819160 TI - Frequency, character and predisposing factor of headache among students of medical college of Karachi. AB - OBJECTIVE: To evaluate the frequency, predisposing factors and symptomatology of headache among medical students. METHODS: The cross-sectional study was conducted from September to December 2013 and comprised students of two medical colleges of Karachi. International Classification of Headache Disorder-II criterion was used to diagnose and classify headache. SPSS 17 was used for statistical analysis. RESULTS: Of the 413 medical students studies, 326(79%) had tension type headache, and 87 (21%) had migraine. Headache was more frequent among females than males, with a ratio of 6.5:1. Both types of headache were significantly associated with self-reported disturbed sleep pattern, stress and various triggering factors (p<0.05 each). Both types greatly influenced individual's daily life with significant association with avoiding academics, extra-curricular activities, family and friends (p<0.05 each). High self-medication rate of 400(96.9%) was observed. CONCLUSIONS: The prevalence of headache among medical students was high with female predominance. Infrequent consultation needs to be addressed through awareness programmes. PMID- 26819162 TI - Prevalence and epidemiology of blood borne pathogens in health care workers of Rawalpindi/Islamabad. AB - OBJECTIVE: To attempt to trace the molecular epidemiology of blood-borne diseases in the hospital community of Pakistan. METHODS: The cross-sectional study was conducted at three major hospitals of Rawalpindi and Islamabad from January to May, 2014.The prevalence of three blood-borne pathogens hepatitis B and C as well as human immunodeficiency virus was investigated in hospital workers of different occupations. Initial screening was performed with immuno-chromatographic technique followed by enzyme-linked immune-sorbent assay. Positive samples were subjected to real time polymerase chain reaction amplification of specific viral sequences for amplification with universal as well as genotype-specific primers. RESULTS: Out of total 500 subjects, there were 42(8.4%) doctors, 101(20.2%) nurses, 92(18.4%) technicians, 67(13.4%) ward boys, 41(8.2%) sweepers, 36(7.2%) security guards and 122(24.4%) administrative workers. None was positive for the presence of human immunodeficiency virus after initial screening with immuno chromatographic technique. In case of hepatitis viruses, 9(0.18%) samples were positive for anti-hepatitis C virus and 3(0.6%) for hepatitis B surface antigen. Three (2.97%) nurses and 3(3.29%) lab technicians were at the highest risk of exposure. CONCLUSIONS: Human immunodeficiency virus was not present among the healthcare workers, while the prevalence of hepatitis B and C viruses was far less compared to the general population. PMID- 26819163 TI - Effect of continued professional development on clinical performance in a public sector health care setting. AB - OBJECTIVE: To determine the effectiveness of intervention by education of doctors in improving the referral rate and quality in a public-sector healthcare setting. METHODS: The quasi-experimental study was conducted from March to September 2012 at PNS Rahat Hospital in naval sailors' residential estate, Karsaz, Karachi. Two awareness sessions were held three months apart by a gynaecologist and a paediatrician. The sessions were aimed at communicating the consultant practice to female general practitioners employed at the two family welfare centres. Pre- and post-intervention data was collected manually from the record registers at the two centers as well as gynaecology and paediatrics outpatient clinics. RESULTS: The study comprised 10 female GPs. In paediatric clinic, there was 47% (118 post intervention/ 187 pre intervention) reduction in referrals for acute gastroenteritis and fever of unknown origin (32 post intervention/75 pre intervention). In gynaecology, 30% (50 post intervention/61 pre intervention) reduction was seen in referrals for severe anaemia in 2nd and 3rd trimesters of pregnancy, and an increase in referrals (35 post intervention/19 pre intervention) for high-risk cases indicating better counselling and case identification. Improved standard of counselling was also reflected by 31% reduced referrals (40 post intervention/ 58 pre intervention) for hyper-emesis gravidarum during the first trimester. The difference in referrals was not statistically significant (p>0.05) for paediatrics, but it was highly significant (p<0.001) for gynaecology. CONCLUSIONS: Healthcare system can function optimally with focus on referral standards and by improving the communication between the primary care physicians and consultants. PMID- 26819164 TI - Women with pregnancy induced hypertension have a higher risk of developing essential hypertension - a case control study from a tertiary care center in Pakistan. AB - OBJECTIVE: To determine the association of essential hypertension with pregnancy induced hypertension in women. METHODS: The case-control study was conducted at Aga Khan University Hospital, Karachi, from January 2012 to March 2013, and comprised on hypertensive female patients who visited the outpatient medicine clinics. The patients were aged 18-65 years and had been pregnant atleast once. Cases were women diagnosed as hypertensive or pre-hypertensive and the controls were normotensive women. The primary outcome was essential hypertension and the main exposure was pregnancy-induced hypertension. RESULTS: Of the 258 subjects, 175(49.7%) were cases and 177(50.3%) were controls. The overall mean age was 44.6+/-13.3 years. Odds Ratio (95% Confidence interval) for pregnancy-induced hypertension for the outcome of essential hypertension was 1.6 (0.88, 3.0). The odds ratio increased further to 2.5(1.2, 5.2) after adjustment for age, family history of hypertension and physical activity. The association remained after further adjusting for body mass index in the final model; 2.20 (1.06, 4.57). CONCLUSIONS: Women who develop hypertension in pregnancy are at higher risk of developing essential hypertension later in life. PMID- 26819165 TI - Awareness of academic use of smartphones and medical apps among medical students in a private medical college? AB - OBJECTIVE: To assess the awareness of medical apps and academic use of smartphones among medical students. METHODS: The questionnaire-based descriptive cross-sectional study was conducted in January 2015 and comprised medical students of the Rawal Institute of Health Sciences, Islamabad, Pakistan. The self designed questionnaire was reviewed by a panel of expert for content reliability and validity. Questionnaires were distributed in the classrooms and were filled by the students anonymously. SPSS 16 was used for statistical analysis. RESULTS: Among the 569 medical students in the study, 545 (95.8%) had smartphones and 24(4.2%) were using simple cell phones. Overall, 226(41.46%) of the smart phone users were using some medical apps. Besides, 137(24.08%) were aware of the medical apps but were not using them. Also, 391(71.7%) students were not using any type of medical text eBooks through their phone, and only 154(28.3%) had relevant text eBooks in their phones. CONCLUSIONS: Medical college students were using smartphones mostly as a means of telecommunication rather than a gadget for improving medical knowledge. PMID- 26819166 TI - Long term survival and impact of various prognostic factors in T1, T2 oral tongue cancer in Pakistan. AB - OBJECTIVE: To determine the outcome in patients with early squamous cell carcinoma of oral tongue, and the impact of various prognostic factors on survival. METHODS: The retrospective study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised records of patients treated for squamous cell carcinoma of early stage tongue between March 2003 and October 2009. Various factors, including demographics, risk factors, stage, and grade of the tumour were determined. Kaplan Meier curves were plotted to determine the 5-year overall survival, relapse-free survival, local control, regional control, and loco-regional control. RESULTS: A total of 137 patients with early oral tongue tumours were treated. With a median follow-up of 46 months, the overall survival of T1, T2 early tongue tumour was 73% and 64%. The incidence of occult metastasis was 30%. The overall survival for Stage I/II and III/IV was 78% and 50% (p=0.002). Patterns of failures included; local 19 (13%), regional 22 (16%), loco-regional 4 (3%) and distant 5 (4%) respectively. The 5-year local control, regional control, loco-regional control was 86%, 82% and 72%. The only significant predictor of overall survival was clinical and pathological N stage in T1 patients, and surgical procedure, grade, pathological N stage in T2 cases. CONCLUSIONS: Treatment of early squamous cell carcinoma of oral tongue effectively achieved local control and disease-free survival. Nodal stage was the most important prognostic factor in terms of survival and recurrence. PMID- 26819167 TI - To asses inter- and intra-observer variability for breast density and BIRADS assessment categories in mammographic reporting. AB - OBJECTIVE: To evaluate the inter- and intra-observer variability among radiologists in the characterisation of mammograms according to Breast Imaging Reporting and Data System assessment and breast density categories. METHODS: The descriptive cross-sectional study was conducted at Aga Khan University Hospital, Karachi, from January 2014 to June 2014. Using non-probability purposive sampling, all mammograms in the study were interpreted by three radiologists on the basis of Breast Imaging Reporting and Data System categories and by assessing the breast density composition. The inter-observer variability was recorded by comparing the difference in the interpretation and categorisation of each case. Intra-observer variability was noted by comparing the differences in the two sets of results from reading the same mammogram three months apart. RESULTS: A total of 254 mammograms were reviewed and the mean age of patients was 55.2+/-11.6 years. In the first round of diagnostic imaging, there was moderate agreement among all three possible pairs of observers regarding breast density (k= 0.50 0.41), but for Breast Imaging Reporting and Data System categories the agreement was less (k=0.27-0.13). After 3 months, variability of observer 1 showed substantial agreement (k=0.65).Variability between observer 2 and observer 3 showed moderate agreement (k=0.13).In terms of categories, intra-observer differences were variable: observer 1 (?=0.61; observer 2(?=0.17); observer 3 (k=0.45). CONCLUSIONS: Despite standardised guidelines for reporting density and assessment categories, observer variability continues to exist. PMID- 26819168 TI - Learning approaches and performance of medical students. AB - OBJECTIVE: To identify the best assessment method for medical students with different learning approaches. METHODS: The cross-sectional questionnaire-based study was conducted at Bahria University Medical and Dental College, Karachi, from March 2010 to April 2011, and comprised first year medical students. The questionnaire was tailored from the Approaches and Study Skills Inventory for Students on a five-point scale Deep approach, Surface apathetic approach and Strategic approach were assessed through relevant sub-scales. Response to questions was summed for the subscales and main scales for a learning approach. Mean scores for aggregate marks obtained by multiple choice questions, short answer questions, problem-based learning and objective structured physical examination were derived. Coefficient of variation was estimated to find the most reliable assessment method. RESULTS: Of the 100 students enrolled, 98(98%) completed the study. Of them, 51(52%) were girls and 47(48%) were boys. Overall, 70(71.4%) students displayed Strategic approach, and 13(13.3%) showed Surface apathetic approach. Objective structured physical examination had the least variation (12.27) for all approaches whereas maximum variation (14.92) was observed by problem-based learning scores. CONCLUSIONS: Assessment by problem based learning scores was able to demarcate deep learners whereas consistent scores were obtained by objective structured physical examination which failed to discriminate variance in performance by different learners. PMID- 26819169 TI - Frequency of intrahepatic cholestasis of pregnancy in Punjab Pakistan: A single centre study. AB - OBJECTIVE: To find out the frequency of intrahepatic cholestasis of pregnancy and its identification parameters. METHODS: The cross-sectional observational study was conducted in the Department of Medicine and the Department of Obstetrics, Combined Military Hospital, Kharian, from October 2013 to March 2014, and comprised all pregnant patients having symptoms suggestive of intrahepatic cholestasis which was confirmed after systemic inquiry, examination and biochemical analysis. Patients with cholestasis due to another reason, coagulopathies, thrombocytopenia and tumours were excluded. The patients were followed up till delivery to see the effects of cholestasis on mother and child. RESULTS: Out of 1001 obstetric patients, 31(3.1%) had intrahepatic cholestasis of pregnancy. Pruritus was the main symptom in 25 (85%) patients followed by rash in 20 (65%). In 20 (64%) patients, labour was induced. Mode of delivery was Caesarean Section in 18 (58%) patients and 9 (29%) had postpartum haemorrhage. Regarding neonatal complications, 22 (70%) required admission to neonatal intensive care and 15 (48%) had meconium aspiration. CONCLUSIONS: A high frequency of intrahepatic cholestasis of pregnancy was observed. It had significant impact on maternal and foetal health. PMID- 26819170 TI - How to improve outcome in surgery for Proximal Hypospadias? AB - OBJECTIVE: To evaluate the role of subdartos fascial tissue as watertight layer in improving outcome for 2-stage proximal hypospadias surgery. METHODS: The experimental study was conducted at the Department of Urology, Indus Hospital, Karachi, and comprised an audit of patients with proximal hypospadias who underwent surgery from July 1, 2007, to December 31, 2011. The initial two-stage repair of proximal hypospadias led to a high rate of urethrocutanous fistula formation (Group A), and, thus, a modification was introduced and subdartos facial double layer was applied over the urethral suture line (Group B). The results were compared regarding age, type of hypospadias, graft failure and urethrocutanous fistula in these patients. RESULTS: There were 27 patients in Group A and 16(59.3%) of them ended up having urethrocutanous fistula. Group B had 25 patients and only 2(8%) had fistula formation. CONCLUSIONS: The application of dartos facial flap waterproofing layer reduced fistula rate. PMID- 26819171 TI - Congenital lobar emphysema. AB - Congenital lobar emphysema is a rare variety of congenital malformation of lung characterized by over distension of a lobe of the lung due to partial obstruction of the bronchus. It is one of the rare causes of infantile respiratory distress requiring surgical resection of affected lobe. We are reporting the case of an 8 week-old baby who presented with respiratory distress related to CLE affecting the left upper lobe. Lobectomy was performed under general anaesthesia followed by an uneventful recovery. PMID- 26819172 TI - Fluorosis... causing paraplegia... mutilating life... AB - Fluorosis is thought to be rare in Pakistan but endemic in various parts of the world, especially in India and China. In Pakistan only a few cases have been reported from Thar, Sibbi and Manga Mandi, with probability of fluorosis on MRI findings, supported by high drinking waterfluoride content. Neurological manifestations of skeletal fluorosis may vary from radiculo-myelopathy to neuropathy. A case of 26 years old female from Thul, Sindh, who presented with paraplegia, is reported here. Her MRI showed extensive classical degenerative changes throughout the spine, consistent with fluorosis, leading to cord compression at multiple levels. No such case with confirmed fluorosis has been previously reported from Pakistan. PMID- 26819173 TI - Fibromatosis of infratemporal space. AB - Fibromatosis is a rare benign mesenchymal neoplasm which primarily originates in the muscle, connective tissue, fascial sheaths, and musculoaponeurotic structures. It is commonly seen as abdominal tumour but in maxillofacial region, the occurrence of these tumours is very rare and exceedingly rare in infratemporal space. Often misdiagnosed due to its varied clinical behaviour, fibromatosis is benign, slow-growing, infiltrative tumour without any metastatic potential, but is locally aggressive causing organ dysfunction along with high recurrence rate. We report a case of fibromatosis involving the left infratemporal space in a 35-year-old female who presented with chief complaint of limited mouth opening for the preceding 4 years. PMID- 26819174 TI - IgG4-related retroperitoneal fibrosis: A case report and review of literature. AB - Idiopathic Retroperitoneal fibrosis is a rare clinical condition recently identified as an autoimmune process related to Immunoglobulin G4 (IgG4) deposition. Herein we report a case of a 46 year old male presenting with 4 months history of backache, fever, flank pain and leg swelling for 2 weeks. Investigations revealed acute kidney injury diagnosed as a result of bilateral ureteric obstruction. This was later confirmed to be retroperitoneal fibrosis on CT scan and biopsy. Histopathology was consistent with IgG4 related disease. Treatment with immunosuppressive agents showed reduction in the fibrosis and normalization of the kidney functions. We discuss the IgG4 related retroperitoneal fibrosis in detail along with its varied presentations. PMID- 26819175 TI - Myocardial injury and acute renal failure associated with lactic acidosis due to suicide attempt with metformin. AB - Metformin-associated lactic acidosis (MALA) is one of the most important drug toxicities with a high morbidity and mortality rate. We report herein a case of suicide attempt with metformin presenting as MALA and acute renal failure on admission to emergency department and acute myocardial injury later on hospitalisation. An obvious improvement of metabolic parameters was seen in our patient provided by anti-ischaemic treatment together with bicarbonate infusion and haemodialysis. Although myocardial injury due to MALA is not a common disorder, we must be aware that metformin overdose with lack of tissue oxygenation, hypoperfusion, and arrhythmias may cause myocardial ischaemia. PMID- 26819176 TI - Large abdominal cystic masses: Report of seven cases. AB - Cystic abdominal tumours are encountered quite often and are diagnosed more frequently due to the availability of better imaging possibilities. Presentation of huge cysts has become rare as most of them are diagnosed and treated early. But we still have patients with enlarged abdominal cysts; majority with cases of serous cystadenomas of the ovary. Absolute diagnosis is only possible with laparotomy and histopathological findings. In this report, seven patients with enlarged gynaecological or mesenteric cystic masses and gastroenterological symptoms are reported. Four of these cases were serous cystadenoma, two were mucinous cystadenoma and one was a paratubal cyst. Gynaecological tumours and mesenteric cysts should not be missed in female patients showing gastrointestinal symptoms. PMID- 26819177 TI - Addressing Insulin Misperceptions (AIM) - Part 2. AB - This article is the second in the series of Addressing Insulin Misperceptions (AIM). It structures perceived objections to insulin according to those prevalent at initiation and intensification, and suggests specific interventions for the commonly encountered misperceptions. The article reflects the need for dialogue in the diabetes clinic: a careful history-taking, involving focused listening, will help identification of misperceptions, and allow crafting of an appropriate strategy to dispel them. PMID- 26819178 TI - The A1C Prandial Product: An objective tool to decision making in diabetes. AB - This brief article describes a numerical index designed to assess the relative contribution of fasting and postprandial glucose to hyperglycaemia. This helps plan appropriate insulin and oral glucose-lowering therapy in an objective manner. It also reviews three similar indices described earlier in literature. Such indices need to be validated in large, multicentric trials, and have the potential to bring objectivity to choice of treatment of diabetes. PMID- 26819179 TI - Calciphylaxis, a rare disease with fatal outcome. PMID- 26819180 TI - Practices of self-medication with antibiotics among nursing students of Institute of Nursing, Dow University of Health Sciences, Karachi, Pakistan. AB - Self-medication practice among nursing students is of growing concern. Access to drugs and handling them in their future practices make nursing students susceptible to self-prescription and self-medication. This cross-sectional study assesses the prevalence and pattern of self-medication with antibiotics among nursing students of Institute of Nursing, Dow University of Health Sciences, Karachi, Pakistan. A random sample of convenience of 160 nursing students underwent a predesigned questionnaire. More than half of nursing students 79 (52.7%) experienced self-medication with antibiotics. It was more prevalent among males 49 (62%) . Knowledge about the drug 59 (74.7%) and convenience 13 (16.5%) were the key reasons to self-medicate. Fever 37 (46.8%) and sore throat 27 (34.2%) were the common symptoms predisposing to self-medication. Beta-lactam group of antibiotics 35 (44.3%) was most frequent used. Only 26 (32.9%) respondents completed the entire antibiotic course. Efforts must be directed towards educating nursing students about responsible and informed self-medication practices. PMID- 26819181 TI - A Qualitative Study on Unassisted Smoking Cessation Among Chinese Canadian Immigrants. AB - It is well-known that majority of smokers worldwide quit smoking without any assistance. This is even more evident among Chinese smokers. The aim of this qualitative study was to explore how Chinese Canadian immigrant men who smoked cigarettes perceived smoking cessation aids and services and how they used any form of the smoking cessation assistance to help them quit smoking. The study was conducted in British Columbia, Canada. Twenty-two Chinese immigrants were recruited by internet advertisement and through connections with local Chinese communities. Ten of the 22 participants were current smokers and the other 12 had quit smoking in the past 5 years. Data were collected using semistructured interviews. Although all participants, including both the ex-smokers and current smokers, had made more than one quit attempt, they rarely used cessation aids or services even after they had immigrated to Canada. The barriers to seeking the cessation assistance were grouped into two categories: practical barriers and cultural barriers. The practical barriers included "Lack of available information on smoking cessation assistance" and "Difficulty in accessing smoking cessation assistance," while cultural barriers included "Denial of physiological addiction to nicotine," "Mistrust in the effectiveness of smoking cessation assistance," "Tendency of self-reliance in solving problems," and "Concern of privacy revelation related to utilization of smoking cessation assistance." The findings revealed Chinese immigrants' unwillingness to use smoking cessation assistance as the result of vulnerability as immigrants and culturally cultivated masculinities of self-control and self-reliance. PMID- 26819182 TI - Dietary Patterns and Their Relationship With Semen Quality. AB - Diet is a complex exposure variable, which calls for multiple approaches to examine the relationship between diet and disease risk. To address these issues, several authors have recently proposed studying overall dietary patterns by considering how foods and nutrients are consumed in combinations. The aim of the study was to investigate the associations between dietary patterns, semen quality parameters, and the level of reproductive hormones. The study population consisted of 336 men who attended the infertility clinic for diagnostic purposes and who had normal semen concentration of 20 to 300 mln/ml or slight oligozoospermia (semen concentration of 15-20 mln/ml). Participants were interviewed, and a semen sample was provided by them. Diet was assessed via food frequency questionnaire, and dietary patterns were identified by factor analysis. Men were classified into three groups according to scores of each dietary pattern: Western, Mixed, or Prudent. A positive association was observed between sperm concentration and Prudent dietary pattern, and level of testosterone and Prudent dietary pattern ( p = .05, p = .03, respectively). Additionally, Prudent dietary pattern was identified to decrease the DNA fragmentation index ( p = .05). The results were adjusted for sexual abstinence, age, smoking, past diseases, and alcohol consumption. Higher consumption of a Prudent dietary pattern was associated with higher sperm concentration and higher level of testosterone. Sperm chromatin structure was inversely related to higher consumption of a Prudent dietary pattern. Further research is needed to confirm these findings and extend these results to other populations. PMID- 26819183 TI - A Pilot Study Using a Web Survey to Identify Characteristics That Influence Hypogonadal Men to Initiate Testosterone Replacement Therapy. AB - Men with hypogonadism (HG) who choose testosterone replacement therapy (TRT) may have distinct characteristics that provide insight as to why they may/may not initiate therapy. The aim of the current study was to identify trends in patient characteristics and attitudes in men diagnosed with HG who initiated TRT (TRT+) compared with men who were diagnosed with HG but did not initiate TRT (TRT-). The market research-based online survey conducted between 2012 and 2013 included patients from a Federated Sample, a commercially available panel of patients with diverse medical conditions. The current analysis was composed of two groups: TRT+ ( n = 155) and TRT- ( n = 157). Patient demographics, clinical characteristics, and attitudes toward HG and TRT were examined as potential predictors of primary adherence in men with HG; cohorts were compared by using Fisher's exact test. Significant associations among sexual orientation, relationship status, educational level, presence of comorbid erectile dysfunction, area of residence, and TRT initiation were present ( p <= .05). College-educated, heterosexual, married men with comorbid erectile dysfunction living in suburban and urban areas were more likely to initiate treatment. The most bothersome symptoms reported were lack of energy (90% vs. 81%, p = .075), decreased strength and endurance (86% vs. 76%, p = .077), and deterioration in work performance (52% vs. 31%, p = .004); lack of energy prompted men to seek help. Patients (48%) in the TRT+ group were more knowledgeable regarding HG as compared with TRT- respondents (14%, p < .001), and most men obtained their information from a health care professional (89% vs. 82%, p = .074). The current analysis identified distinct demographic and clinical characteristics and attitudes among TRT users compared with men who were diagnosed with HG yet remained untreated. PMID- 26819184 TI - PtrWRKY19, a novel WRKY transcription factor, contributes to the regulation of pith secondary wall formation in Populus trichocarpa. AB - WRKY proteins are one of the largest transcription factor families in higher plants and play diverse roles in various biological processes. Previous studies have shown that some WRKY members act as negative regulators of secondary cell wall formation in pith parenchyma cells. However, the regulatory mechanism of pith secondary wall formation in tree species remains largely unknown. In this study, PtrWRKY19 encoding a homolog of Arabidopsis WRKY12 was isolated from Populus trichocarpa. PtrWRKY19 was expressed in all tissues tested, with highest expression in stems, especially in pith. PtrWRKY19 was located in the nucleus and functioned as a transcriptional repressor. Ectopic expression of PtrWRKY19 in an atwrky12 mutant successfully rescued the phenotype in pith cell walls caused by the defect of AtWRKY12, suggesting that PtrWRKY19 had conserved functions for homologous AtWRKY12. Overexpression of PtrWRKY19 in poplar plants led to a significant increase in the number of pith parenchyma cells. qRT-PCR analysis showed that lignin biosynthesis-related genes were repressed in transgenic plants. In transcient reporter assays, PtrWRKY19 was identified to repress transcription from the PtoC4H2 promoter containing the conserved W-box elements. These results indicated that PtrWRKY19 may function as a negative regulator of pith secondary wall formation in poplar. PMID- 26819185 TI - Absence of human rhinovirus and respiratory syncytial virus from bronchoalveolar lavage and bronchial biopsies of selected patients with stable chronic obstructive pulmonary disease. AB - Previous studies have reported very different rates of human rhinovirus (HRV) and respiratory syncytial virus (RSV) genome detection in nasal and sputum samples, but not in bronchoalveolar lavage (BAL) and bronchial biopsy samples. Our study aimed to investigate the presence of HRV and RSV in the lungs of 31 consecutive patients with stable COPD (11 GOLD stage I, 11 II, and 9 III) and 22 control subjects (12 current or past smokers, and 10 non-smokers), who underwent diagnostic (e.g., lung cancer) and/or therapeutic (e.g., hemoptysis) fibreoptic bronchoscopy in a university hospital in Athens, Greece. Viral RNA of HRV and RSV were not detected in any of the samples of COPD patients or control subjects after being processed with real-time PCR. PMID- 26819186 TI - Safety and Efficacy of Minimally Invasive Video-Assisted Ablation of Pilonidal Sinus: A Randomized Clinical Trial. AB - IMPORTANCE: Video-assisted ablation of pilonidal sinus (VAAPS) is a new minimally invasive treatment based on the complete removal of the sinus cavity with a minimal surgical wound. OBJECTIVE: To validate the safety and efficacy of VAAPS. DESIGN, SETTING, AND PARTICIPANTS: From January 1, 2012, through December 31, 2013, we enrolled 145 consecutive patients from an intention-to-treat population at a single academic center in Italy. The last date of follow-up for this analysis was December 31, 2014. Patients with chronic nonrecurrent pilonidal sinus were randomized to minimally invasive (76 patients) or conventional (69 patients) treatment of pilonidal sinus. INTERVENTIONS: VAAPS and Bascom cleft lift procedure. MAIN OUTCOMES AND MEASURES: The primary end point of the study was time off work. Secondary end points were the rates of operative success and perioperative complications (infection and recurrence), operative time, patient satisfaction, and intraoperative and postoperative pain ratings. RESULTS: Of the 145 patients, 60 (78.9%) were male and 16 (21.1%) were female in the minimally invasive treatment group, and 54 (78.3%) were male and 15 (21.7%) were female in the conventional treatment group. The mean (SD) age of the patients was 25.5 (5.9) years in the minimally invasive treatment group and 25.7 (5.3) in the conventional treatment group. In the minimally invasive treatment group, mean (SD) time off work was significantly less compared with the conventional treatment group (1.6 [1.7] vs 8.2 [3.9] days; P < .001). Mean (SD) operative time was significantly longer in the minimally invasive treatment group (42.9 [9.8] minutes) vs the conventional treatment group (26.5 [8.7] minutes), P < .001. Although the overall complication rate was similar in both groups, there were fewer infections (1 [1.3%] vs 5 [7.2%]; P = .10) recorded in the minimally invasive treatment group. Similarly, patients enrolled in the minimally invasive treatment group expressed significantly less pain and higher satisfaction. CONCLUSIONS AND RELEVANCE: In the new era of minimally invasive treatment surgery, pilonidal sinus could become a disease treated with an endoscopic approach. Although additional studies are needed to provide a definitive conclusion, our results encourage considering the adoption of this treatment as the most effective way to treat pilonidal sinus. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01963273. PMID- 26819187 TI - The right diagnosis but the wrong pathway? Listeria meningitis mimicking stroke. PMID- 26819188 TI - Autoimmune limbic encephalitis due to VGKC-Ab. Thanks for the memory. Leo Robin (Title of song, 1937). PMID- 26819189 TI - Friction and conductance imaging of sp(2)- and sp(3)-hybridized subdomains on single-layer graphene oxide. AB - We investigated the subdomain structures of single-layer graphene oxide (GO) by characterizing local friction and conductance using conductive atomic force microscopy. Friction and conductance mapping showed that a single-layer GO flake has subdomains several tens to a few hundreds of nanometers in lateral size. The GO subdomains exhibited low friction (high conductance) in the sp(2)-rich phase and high friction (low conductance) in the sp(3)-rich phase. Current-voltage spectroscopy revealed that the local current flow in single-layer GO depends on the quantity of hydroxyl and carboxyl groups, and epoxy bridges within the 2 dimensional carbon layer. The presence of subdomains with different sp(2)/sp(3) carbon ratios on a GO flake was also confirmed by chemical mapping using scanning transmission X-ray microscopy. These results suggest that spatial mapping of the friction and conductance can be used to rapidly identify the composition of heterogeneous single-layer GO at nanometer scale, which is essential for understanding charge transport in nanoelectronic devices. PMID- 26819190 TI - Periocular dirofilariasis: A case series. AB - OBJECTIVE: To cite a series of patients presenting with complaints of a lid swelling associated with preseptal cellulitis. METHODS: Three patients on three different occasions came with complaints of a unilateral lid swelling associated with preseptal cellulitis. Examination showed palpable mass in the upper eyelid localized, firm in consistency and was freely mobile and occasionally disappeared during palpation. CT scan showed nonspecific preseptal inflammation. A trial of antibiotics was given in each of the cases with temporary reduction in the swelling but a consecutive flare up following which patient was subjected to excision biopsy. Each of the biopsies was subjected to histopathological and microbiological examination. RESULTS: On excision biopsy in all the three cases it was reported to be a parasitic infestation belonging to the genus Dirofilaria. CONCLUSIONS: Dirofilariaiasis is a common zoonotic infection among wild animals but rarely infects human beings with ocular involvement. Hence dirofilariasis should be considered as a differential diagnosis for migratory subcutaneous swellings and conjunctival nodules in the southern belt of India. PMID- 26819191 TI - Explosive Contagion in Networks. AB - The spread of social phenomena such as behaviors, ideas or products is an ubiquitous but remarkably complex phenomenon. A successful avenue to study the spread of social phenomena relies on epidemic models by establishing analogies between the transmission of social phenomena and infectious diseases. Such models typically assume simple social interactions restricted to pairs of individuals; effects of the context are often neglected. Here we show that local synergistic effects associated with acquaintances of pairs of individuals can have striking consequences on the spread of social phenomena at large scales. The most interesting predictions are found for a scenario in which the contagion ability of a spreader decreases with the number of ignorant individuals surrounding the target ignorant. This mechanism mimics ubiquitous situations in which the willingness of individuals to adopt a new product depends not only on the intrinsic value of the product but also on whether his acquaintances will adopt this product or not. In these situations, we show that the typically smooth (second order) transitions towards large social contagion become explosive (first order). The proposed synergistic mechanisms therefore explain why ideas, rumours or products can suddenly and sometimes unexpectedly catch on. PMID- 26819192 TI - Seeking population-level solutions to obesity. PMID- 26819193 TI - Effects of obesity on hormonally driven cancer in women. AB - Obesity increases the risk of numerous poor health outcomes, including cancer. Obesity is especially problematic in women because both they and their offspring may be at increased risk of cancer. Studying transmission of obesity-induced cancer risk is challenging in humans, but animal studies are beginning to reveal the underlying mechanisms. PMID- 26819194 TI - Hyaluronan in adipose tissue: Beyond dermal filler and therapeutic carrier. AB - Adipose hyaluronan is increasingly recognized as an active player in adipose tissue fibrosis and metabolic dysfunction. However, this role poses as many challenges as opportunities for therapeutic targeting of adipose tissue dysfunction during nutrient oversupply. PMID- 26819195 TI - Complex effects of inhibiting hepatic apolipoprotein B100 synthesis in humans. AB - Mipomersen is a 20mer antisense oligonucleotide (ASO) that inhibits apolipoprotein B (apoB) synthesis; its low-density lipoprotein (LDL)-lowering effects should therefore result from reduced secretion of very-low-density lipoprotein (VLDL). We enrolled 17 healthy volunteers who received placebo injections weekly for 3 weeks followed by mipomersen weekly for 7 to 9 weeks. Stable isotopes were used after each treatment to determine fractional catabolic rates and production rates of apoB in VLDL, IDL (intermediate-density lipoprotein), and LDL, and of triglycerides in VLDL. Mipomersen significantly reduced apoB in VLDL, IDL, and LDL, which was associated with increases in fractional catabolic rates of VLDL and LDL apoB and reductions in production rates of IDL and LDL apoB. Unexpectedly, the production rates of VLDL apoB and VLDL triglycerides were unaffected. Small interfering RNA-mediated knockdown of apoB expression in human liver cells demonstrated preservation of apoB secretion across a range of apoB synthesis. Titrated ASO knockdown of apoB mRNA in chow-fed mice preserved both apoB and triglyceride secretion. In contrast, titrated ASO knockdown of apoB mRNA in high-fat-fed mice resulted in stepwise reductions in both apoB and triglyceride secretion. Mipomersen lowered all apoB lipoproteins without reducing the production rate of either VLDL apoB or triglyceride. Our human data are consistent with long-standing models of posttranscriptional and posttranslational regulation of apoB secretion and are supported by in vitro and in vivo experiments. Targeting apoB synthesis may lower levels of apoB lipoproteins without necessarily reducing VLDL secretion, thereby lowering the risk of steatosis associated with this therapeutic strategy. PMID- 26819197 TI - The intersection of nonalcoholic fatty liver disease and obesity. AB - Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and recently emerged as the most rapidly increasing indication for liver transplant. Although obesity is a risk factor for NAFLD, overlap between these two entities is incompletely understood. We highlight recent insights into the pathogenesis of human NAFLD in relation to obesity and discuss advances in the diagnosis and treatment of NAFLD. PMID- 26819198 TI - New therapeutic approaches for the treatment of obesity. AB - This review discusses current and future pharmacological approaches to the treatment of obesity, with a focus on the biological control of energy balance. PMID- 26819196 TI - USF1 deficiency activates brown adipose tissue and improves cardiometabolic health. AB - USF1 (upstream stimulatory factor 1) is a transcription factor associated with familial combined hyperlipidemia and coronary artery disease in humans. However, whether USF1 is beneficial or detrimental to cardiometabolic health has not been addressed. By inactivating USF1 in mice, we demonstrate protection against diet induced dyslipidemia, obesity, insulin resistance, hepatic steatosis, and atherosclerosis. The favorable plasma lipid profile, including increased high density lipoprotein cholesterol and decreased triglycerides, was coupled with increased energy expenditure due to activation of brown adipose tissue (BAT). Usf1 inactivation directs triglycerides from the circulation to BAT for combustion via a lipoprotein lipase-dependent mechanism, thus enhancing plasma triglyceride clearance. Mice lacking Usf1 displayed increased BAT-facilitated, diet-induced thermogenesis with up-regulation of mitochondrial respiratory chain complexes, as well as increased BAT activity even at thermoneutrality and after BAT sympathectomy. A direct effect of USF1 on BAT activation was demonstrated by an amplified adrenergic response in brown adipocytes after Usf1 silencing, and by augmented norepinephrine-induced thermogenesis in mice lacking Usf1. In humans, individuals carrying SNP (single-nucleotide polymorphism) alleles that reduced USF1 mRNA expression also displayed a beneficial cardiometabolic profile, featuring improved insulin sensitivity, a favorable lipid profile, and reduced atherosclerosis. Our findings identify a new molecular link between lipid metabolism and energy expenditure, and point to the potential of USF1 as a therapeutic target for cardiometabolic disease. PMID- 26819199 TI - Ignorance about sepsis was a factor in child's death, says report. PMID- 26819200 TI - Investigation into the acute effects of total and partial energy restriction on postprandial metabolism among overweight/obese participants. AB - The intermittent energy restriction (IER) approach to weight loss involves short periods of substantial (75-100 %) energy restriction (ER) interspersed with normal eating. This study aimed to characterise the early metabolic response to these varying degrees of ER, which occurs acutely and prior to weight loss. Ten (three female) healthy, overweight/obese participants (36 (SEM 5) years; 29.0 (sem 1.1) kg/m2) took part in this acute three-way cross-over study. Participants completed three 1-d dietary interventions in a randomised order with a 1-week washout period: isoenergetic intake, partial 75 % ER and total 100 % ER. Fasting and postprandial (6-h) metabolic responses to a liquid test meal were assessed the following morning via serial blood sampling and indirect calorimetry. Food intake was also recorded for two subsequent days of ad libitum intake. Relative to the isoenergetic control, postprandial glucose responses were increased following total ER (+142 %; P=0.015) and to a lesser extent after partial ER (+76 %; P=0.051). There was also a delay in the glucose time to peak after total ER only (P=0.024). Both total and partial ER interventions produced comparable reductions in postprandial TAG responses (-75 and -59 %, respectively; both P<0.05) and 3-d energy intake deficits of approximately 30 % (both P=0.015). Resting and meal-induced thermogenesis were not significantly affected by either ER intervention. In conclusion, our data demonstrate the ability of substantial ER to acutely alter postprandial glucose-lipid metabolism (with partial ER producing the more favourable overall response), as well as incomplete energy intake compensation amongst overweight/obese participants. Further investigations are required to establish how metabolism adapts over time to the repeated perturbations experienced during IER, as well as the implications for long-term health. PMID- 26819201 TI - Sleep duration and dietary macronutrient consumption can modify the cardiovascular disease for Korean women but not for men. AB - BACKGROUND: Although the association between cardiovascular disease (CVD) and sleep duration is generally recognized, the results are inconsistent, and investigations examining the effects of seep duration and diet on CVD are rare. METHODS: The gender-difference in the effect of the sleep duration on Framingham risk score (FRS)-related factors, 10-year predicted CVD risk, and dietary consumption was analyzed in 14,111 subjects (Men n = 5,727; Women n = 8,384) aged >= 20 from the Korean National Health and Nutrition Examination Survey. RESULTS: The gender difference in the CVD risk factors according to sleep duration was observed. Only women with short sleep durations (<7 h/day) exhibited elevated FRS factors, such as systolic blood pressures (SBP) (P < 0.001), diastolic blood pressures (DBP) (P = 0.008), and the proportion of hypertension (HTN) treatments (P < 0.001), but not for men. Moreover, the 10-year predicted CVD risk, as evaluated with the FRS, was higher in women with short sleep durations (P < 0.001). Women with short sleep durations consumed significantly more dietary carbohydrates (CHO) than those with normal sleep durations (P < 0.001). Additionally, the ORs for intermediate and high 10-year predicted CVD risks and CVD-related factors, such as high age, elevated SBP, and HTN treatment, significantly increased with short sleep durations among women [OR (95 % CI) = 1.709 (1.359-2.149) for CVD risk, 1.976 (1.756-2.224) for high age, 1.535 (1.291 1.826) for elevated SBP, and 1.515 (1.320-1.739) for HTN treatment]. CONCLUSIONS: Short sleep duration influenced dietary carbohydrate consumption and elevated FRS related factors as well as 10-year predicted CVD risk. Our findings demonstrated that the CVD risk has been potentially modified by short sleep durations and greater CHO consumptions. PMID- 26819202 TI - Cutting Edge: The RIG-I Ligand 3pRNA Potently Improves CTL Cross-Priming and Facilitates Antiviral Vaccination. AB - Protective immunity against intracellular pathogens involves the induction of robust CTL responses. Vaccination with protein Ags establishes such responses only when combined with immune-stimulatory adjuvants. In this study, we compared different adjuvants and identified triphosphate RNA (3pRNA) as especially effective at inducing CTL responses. 3pRNA sensing required IPS-1/MAVS signaling and induced type I IFN in plasmacytoid dendritic cells and macrophages, with the latter being more important for the adjuvant effect. Type I IFN acted on CD11c(+) cells, especially on CD8alpha(+) Batf3-dependent dendritic cells. Vaccination with OVA in combination with 3pRNA protected mice from a subsequent OVA-encoding adenovirus infection in a CD8(+) cell-dependent manner and more efficiently than other adjuvants. In summary, 3pRNA is a superior adjuvant for CTL activation and might be useful to facilitate antiviral immunization strategies. PMID- 26819203 TI - IRF6 Regulates the Expression of IL-36gamma by Human Oral Epithelial Cells in Response to Porphyromonas gingivalis. AB - IFN regulatory factors (IRFs) help to shape the immune response to pathogens by imparting signaling specificity to individual TLRs. We recently demonstrated that IRF6 provides specificity to TLR2 signaling in oral epithelial cells. TLR2 plays an important role in eliciting inflammation to Porphyromonas gingivalis, a keystone pathogen in periodontitis. Therefore, we investigated a role for IRF6 in mediating the inflammatory cytokine response of oral epithelial cells to P. gingivalis. IRF6 expression was strongly upregulated when human oral epithelial cells were challenged with P. gingivalis. Moreover, gene silencing and gene promoter experiments indicated that IRF6 acts downstream of IL-1R-associated kinase 1 to stimulate the expression of the IL-1 family cytokine IL-36gamma in response to P. gingivalis. IRF6 and IL-1R-associated kinase 1 also regulated the stimulation of IL-36gamma expression by a TLR2 agonist. IL-36gamma was shown to elicit inflammatory responses by human monocyte-derived dendritic cells and macrophages, including the expression of the neutrophil chemokines IL-8 and CXCL1, as well as the Th17 chemokine CCL20. IL-36gamma similarly stimulated their expression by human oral epithelial cells. Significantly, the Th17 cytokine IL-17 not only stimulated the expression of important regulators of neutrophil recruitment and survival by oral epithelial cells, but IL-17 also stimulated them to express IL-36gamma. Thus, our findings suggest that IRF6 is likely to promote inflammation to P. gingivalis through its regulation of IL-36gamma. PMID- 26819204 TI - Aminobisphosphonates Synergize with Human Cytomegalovirus To Activate the Antiviral Activity of Vgamma9Vdelta2 Cells. AB - Human Vgamma9Vdelta2 T cells are activated through their TCR by neighboring cells producing phosphoantigens. Zoledronate (ZOL) treatment induces intracellular accumulation of the phosphoantigens isopentenyl pyrophosphate and ApppI. Few attempts have been made to use immunomanipulation of Vgamma9Vdelta2 lymphocytes in chronic viral infections. Although Vgamma9Vdelta2 T cells seem to ignore human CMV (HCMV)-infected cells, we examined whether they can sense HCMV when a TCR stimulus is provided with ZOL. Fibroblasts treated with ZOL activate Vgamma9Vdelta2 T cells to produce IFN-gamma but not TNF. Following the same treatment, HCMV-infected fibroblasts stimulate TNF secretion and an increased production of IFN-gamma, indicating that Vgamma9Vdelta2 cells can sense HCMV infection. Increased lymphokine production was observed with most clinical isolates and laboratory HCMV strains, HCMV-permissive astrocytoma, or dendritic cells, as well as "naive" and activated Vgamma9Vdelta2 cells. Quantification of intracellular isopentenyl pyrophosphate/ApppI following ZOL treatment showed that HCMV infection boosts their accumulation. This was explained by an increased capture of ZOL and by upregulation of HMG-CoA synthase and reductase transcription. Using an experimental setting where infected fibroblasts were cocultured with gammadelta cells in submicromolar concentrations of ZOL, we show that Vgamma9Vdelta2 cells suppressed substantially the release of infectious particles while preserving uninfected cells. Vgamma9Vdelta2 cytotoxicity was decreased by HCMV infection of targets whereas anti-IFN-gamma and anti-TNF Abs significantly blocked the antiviral effect. Our experiments indicate that cytokines produced by Vgamma9Vdelta2 T cells have an antiviral potential in HCMV infection. This should lead to in vivo studies to explore the possible antiviral effect of immunostimulation with ZOL in this context. PMID- 26819205 TI - Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut. AB - Helminth infections have been suggested to impair the development and outcome of Th1 responses to vaccines and intracellular microorganisms. However, there are limited data regarding the ability of intestinal nematodes to modulate Th1 responses at sites distal to the gut. In this study, we have investigated the effect of the intestinal nematode Heligmosomoides polygyrus bakeri on Th1 responses to Mycobacterium bovis bacillus Calmette-Guerin (BCG). We found that H. polygyrus infection localized to the gut can mute BCG-specific CD4(+) T cell priming in both the spleen and skin-draining lymph nodes. Furthermore, H. polygyrus infection reduced the magnitude of delayed-type hypersensitivity (DTH) to PPD in the skin. Consequently, H. polygyrus-infected mice challenged with BCG had a higher mycobacterial load in the liver compared with worm-free mice. The excretory-secretory product from H. polygyrus (HES) was found to dampen IFN-gamma production by mycobacteria-specific CD4(+) T cells. This inhibition was dependent on the TGF-betaR signaling activity of HES, suggesting that TGF-beta signaling plays a role in the impaired Th1 responses observed coinfection with worms. Similar to results with mycobacteria, H. polygyrus-infected mice displayed an increase in skin parasite load upon secondary infection with Leishmania major as well as a reduction in DTH responses to Leishmania Ag. We show that a nematode confined to the gut can mute T cell responses to mycobacteria and impair control of secondary infections distal to the gut. The ability of intestinal helminths to reduce DTH responses may have clinical implications for the use of skin test based diagnosis of microbial infections. PMID- 26819206 TI - Chronically Elevated Levels of Short-Chain Fatty Acids Induce T Cell-Mediated Ureteritis and Hydronephrosis. AB - Short-chain fatty acids (SCFAs) are major products of gut microbial fermentation and profoundly affect host health and disease. SCFAs generate IL-10(+) regulatory T cells, which may promote immune tolerance. However, SCFAs can also induce Th1 and Th17 cells upon immunological challenges and, therefore, also have the potential to induce inflammatory responses. Because of the seemingly paradoxical SCFA activities in regulating T cells, we investigated, in depth, the impact of elevated SCFA levels on T cells and tissue inflammation in mice. Orally administered SCFAs induced effector (Th1 and Th17) and regulatory T cells in ureter and kidney tissues, and they induced T cell-mediated ureteritis, leading to kidney hydronephrosis (hereafter called acetate-induced renal disease, or C2RD). Kidney hydronephrosis in C2RD was caused by ureteral obstruction, which was, in turn, induced by SCFA-induced inflammation in the ureteropelvic junction and proximal ureter. Oral administration of all major SCFAs, such as acetate, propionate, and butyrate, induced the disease. We found that C2RD development is dependent on mammalian target of rapamycin activation, T cell-derived inflammatory cytokines such as IFN-gamma and IL-17, and gut microbiota. Young or male animals were more susceptible than old or female animals, respectively. However, SCFA receptor (GPR41 or GPR43) deficiency did not affect C2RD development. Thus, SCFAs, when systemically administered at levels higher than physiological levels, cause dysregulated T cell responses and tissue inflammation in the renal system. The results provide insights into the immunological and pathological effects of chronically elevated SCFAs. PMID- 26819207 TI - Twist may be associated with invasion and metastasis of hypoxic NSCLC cells. AB - Hypoxia promotes tumor invasion and metastasis via multiple mechanisms, including epithelial-mesenchymal transition (EMT). Twist, an EMT regulator, has been disclosed to associate with invasion and metastasis as well as poor prognosis of many malignancies. However, it remains undefined whether Twist is involved in invasion and metastasis of hypoxic non-small cell lung cancer (NSCLC). In this study, protein levels of Twist, hypoxia-inducible factor-1alpha (HIF-1alpha), and EMT markers (E-cadherin and vimentin) were examined by immunohistochemistry in 76 lung cancer tissues from NSCLC patients. Expression of Twist and its correlation with HIF-1alpha, E-cadherin, and vimentin were analyzed. Small interfering RNA (siRNA) against Twist was used to knockdown Twist expression in hypoxic NSCLC cells, A549 and NCI-H460. Cellular invasion and protein levels of Twist, E cadherin, and vimentin were evaluated by matrigel invasion assay and Western blot, respectively. Our results showed that in clinical samples, there was a significant association between Twist expression and differentiation degree, lymph node metastasis, and TNM stage. Correlation analysis demonstrated that expression of Twist was negatively correlated with E-cadherin expression, but positively associated with HIF-1alpha and vimentin expression. In cultured NSCLC cells, Twist messenger RNA (mRNA) and protein levels were upregulated under hypoxia, while knockdown of Twist suppressed potentiated invasion and expression of mesenchymal marker vimentin induced by hypoxia. Protein level of increased epithelial marker E-cadherin was shown along with Twist downregulation. These findings suggest that Twist promoting hypoxic invasion and metastasis of NSCLC may be associated with altered expression of EMT markers. Inhibition of Twist may be of therapeutic significance. PMID- 26819208 TI - Gankyrin regulates cell signaling network. AB - Gankyrin is an oncoprotein that facilitates the degradation of two key tumor suppressors, namely, Rb and p53. Although Gankyrin overexpression was identified in different carcinomas eventually and associated with poor prognosis, its function and mechanism remain not well understood. Recently, the signal transduction mechanisms of Gankyrin have been explored, which may provide new drug targets in tumors overexpressing Gankyrin. In this review, we summarize the significant signal transduction pathways regulated by Gankyrin. PMID- 26819210 TI - Letter regarding "MT1-MMP is not a good prognosticator of cancer survival: evidence from 11 studies" by Wu KP et al. AB - With great interest, we carefully read a meta-analysis entitled "MT1-MMP is not a good prognosticator of cancer survival: evidence from 11 studies" in Tumor Biology (by Wu KP et al.), in which the investigators aimed to assess the association between MT1-MMP expression and prognosis of patients with various types of cancers by calculating the pooled hazard ratio (HR) with corresponding 95 % confidence interval (95 % CI). They have reached an important conclusion that MT1-MMP overexpression indicated an unfavorable overall survival (OS) in cancers and the pooled HR (95 % CI) was 2.46 (95 % CI 1.75-3.47). In addition, subgroup analysis showed the HRs (95 % CI) were 3.73 (95 % CI 2.67-5.21) and 2.46 (95 % CI 1.69-3.59) for MT1-MMP in lung cancer and gastric cancer, respectively. Before these results can be accepted, we would like to address several concerns related to this meta-analysis. PMID- 26819209 TI - Prognostic impact of perioperative lymphocyte-monocyte ratio in patients with bladder cancer undergoing radical cystectomy. AB - Various systemic inflammatory response biomarkers are associated with oncological outcome. We evaluated the superiority of prognostic predictive accuracy between neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR), and the prognostic significance of their perioperative change in patients with bladder cancer undergoing radical cystectomy (RC). We retrospectively analyzed 302 patients who had undergone RC in four institutions. Comparison of predictive accuracy between NLR and LMR was performed using receiver operating characteristic curve analysis. Overall survival (OS) and cancer-specific survival (CSS) were assessed with the Kaplan-Meier method and Cox regression analysis. Preoperative and postoperative LMR showed higher predictive accuracy for OS than NLR did (p = 0.034). Applying a cutoff of 3.41, change in perioperative LMR stratified patients into three groups (low, intermediate, and high risk), showing a significant difference in OS and CSS (p < 0.001, each), and pathological outcomes. Multivariable analyses for OS and CSS showed that poor changes in LMR (high risk) were an independent prognostic factor (hazard ratio 5.70, 95 % confidence interval 3.49-9.32, p < 0.001; hazard ratio 4.53, 95 % confidence interval 2.63-7.82, p < 0.001; respectively). Perioperative LMR is significantly associated with survival in patients with bladder cancer after RC, and it is possibly superior to NLR as a prognostic factor. PMID- 26819211 TI - Erratum to: Differentiation of Human Endometrial Stem Cells into Schwann Cells in Fibrin Hydrogel as 3D Culture. PMID- 26819212 TI - Erratum to: Non-Ceruloplasmin Copper Distincts Subtypes in Alzheimer's Disease: a Genetic Study of ATP7B Frequency. PMID- 26819213 TI - Public availability of results of observational studies evaluating an intervention registered at ClinicalTrials.gov. AB - BACKGROUND: Observational studies are essential for assessing safety. The aims of this study were to evaluate whether results of observational studies evaluating an intervention with safety outcome(s) registered at ClinicalTrials.gov were published and, if not, whether they were available through posting on ClinicalTrials.gov or the sponsor website. METHODS: We identified a cohort of observational studies with safety outcome(s) registered on ClinicalTrials.gov after October 1, 2007, and completed between October 1, 2007, and December 31, 2011. We systematically searched PubMed for a publication, as well as ClinicalTrials.gov and the sponsor website for results. The main outcomes were the time to the first publication in journals and to the first public availability of the study results (i.e. published or posted on ClinicalTrials.gov or the sponsor website). For all studies with results publicly available, we evaluated the completeness of reporting (i.e. reported with the number of events per arm) of safety outcomes. RESULTS: We identified 489 studies; 334 (68%) were partially or completely funded by industry. Results for only 189 (39%, i.e. 65% of the total target number of participants) were published at least 30 months after the study completion. When searching other data sources, we obtained the results for 53% (n = 158; i.e. 93% of the total target number of participants) of unpublished studies; 31% (n = 94) were posted on ClinicalTrials.gov and 21% (n = 64) on the sponsor website. As compared with non-industry-funded studies, industry-funded study results were less likely to be published but not less likely to be publicly available. Of the 242 studies with a primary outcome recorded as a safety issue, all these outcomes were adequately reported in 86% (114/133) when available in a publication, 91% (62/68) when available on ClinicalTrials.gov, and 80% (33/41) when available on the sponsor website. CONCLUSIONS: Only 39% of observational studies evaluating an intervention with safety outcome(s) registered at ClinicalTrials.gov had their results published at least 30 months after study completion. The registration of these observational studies allowed searching other sources (results posted at ClinicalTrials.gov and sponsor website) and obtaining results for half of unpublished studies and 93% of the total target number of participants. PMID- 26819214 TI - [Metabolic and Reproductive Consequences of the Polycystic Ovary Syndrome (PCOS)]. AB - Polycystic ovarian syndrome represents the most common endocrine disease of women of reproductive age. Symptoms include metabolic, gynecologic and cosmetic features. Genetic factors seem to contribute to the disease, affecting not only women but also male relatives of patients with similar symptoms. Besides, lifestyle factors play a central role impacting clinical PCOS appearance. Following we present an overview of the syndrome, its epidemiology, metabolic and gynecological aspects, gender and genetic factors and its therapy. PMID- 26819215 TI - Musculoskeletal imaging in preventive medicine. AB - The aim is to review the modalities in musculoskeletal imaging with view on the prognostic impact for the patient's and for social outcome and with view on three major fields of preventive medicine: nutrition and metabolism, sports, and patient education. The added value provided by preventive imaging is (1) to monitor bone health and body composition with a broad spectrum of biomarkers, (2) to detect and quantify variants or abnormalities of nerves, muscles, tendons, bones, and joints with a risk of overuse, rupture, or fracture, and (3) to develop radiology reports from the widely used narrative format to structured text and multimedia datasets. The awareness problem is a term for describing the underreporting and the underdiagnosis of fragility fractures in osteoporosis. PMID- 26819216 TI - Orphan diseases: state of the drug discovery art. AB - Since 1983 more than 300 drugs have been developed and approved for orphan diseases. However, considering the development of novel diagnosis tools, the number of rare diseases vastly outpaces therapeutic discovery. Academic centers and nonprofit institutes are now at the forefront of rare disease R&D, partnering with pharmaceutical companies when academic researchers discover novel drugs or targets for specific diseases, thus reducing the failure risk and cost for pharmaceutical companies. Considerable progress has occurred in the art of orphan drug discovery, and a symbiotic relationship now exists between pharmaceutical industry, academia, and philanthropists that provides a useful framework for orphan disease therapeutic discovery. Here, the current state-of-the-art of drug discovery for orphan diseases is reviewed. Current technological approaches and challenges for drug discovery are considered, some of which can present somewhat unique challenges and opportunities in orphan diseases, including the potential for personalized medicine, gene therapy, and phenotypic screening. PMID- 26819217 TI - Hybrid Light Imaging Using Cerenkov Luminescence and Liquid Scintillation for Preclinical Optical Imaging In Vivo. AB - PURPOSE: Cerenkov luminescence imaging (CLI) has recently emerged as a molecular imaging modality for radionuclides emitting beta-particles. The aim of this study was to develop a hybrid light imaging (HLI) technique using a liquid scintillator to assist CLI by increasing the optical signal intensity from both beta-particle and gamma-ray emitting radionuclides located at deep regions in vivo. PROCEDURES: A commercial optical imaging system was employed to collect all images by HLI and CLI. To investigate the performance characteristics of HLI with a commercially available liquid scintillator (Emulsifier-safe), phantom experiments were conducted for two typical beta-particle and gamma-ray emitters, sodium iodide (Na[(131)I]I) and 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG), respectively. To evaluate the feasibility of HLI for in vivo imaging, HLI was applied to a Na[(131)I]I injected nu/nu mouse and an [(18)F]FDG injected Balb-c mouse and compared with CLI alone. RESULTS: Measured HLI wavelength spectra with Emulsifier safe showed higher signal intensities than for CLI at 500-600 nm. For material preventing light transmission of 12-mm thickness, CLI imaging provided quite low intensity and obscure signals of the source. However, despite degraded spatial resolution, HLI imaging provided sustained visualization of the source shape, with signal intensities 10-14 times higher than for CLI at 10-mm thickness. Furthermore, at 0, 4, and 8-mm material thicknesses, HLI showed a strong correlation between Na[(131)I]I or [(18)F]FDG radioactivity and signal intensity, as for CLI. In vivo studies also demonstrated that HLI could successfully visualize Na[(131)I]I uptake in the mouse thyroid gland in the prone position and [(18)F]FDG accumulation in the heart in the supine position, which were not observed with CLI. CONCLUSION: Our preliminary studies suggest that HLI can provide enhanced imaging of a beta-particle probe emitting together with gamma rays at deep tissue locations. HLI may be a promising imaging technique to assist with preclinical in vivo imaging using CLI. PMID- 26819218 TI - In vitro antibacterial activity of selected medicinal plants traditionally used in Vietnam against human pathogenic bacteria. AB - BACKGROUND: Medicinal plants are widely used for the treatment of different infectious diseases. Infectious diseases caused by bacteria have a large impact on public health. This study aimed to determine the in vitro antibacterial activity of the medicinal plants traditionally used in Vietnam against the bacterial strains associated with infectious diseases. METHODS: Methanol extracts of twelve Vietnamese medicinal plants were tested for their antibacterial activity against five bacterial species including Gram-positive bacteria (Bacillus cereus, Bacillus subtilis, and Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) using the broth microdilution method. RESULTS: All the plant extracts showed antibacterial activity, especially against Gram-positive bacteria (Bacillus cereus, Bacillus subtilis, and Staphylococcus aureus). Baeckea frutescens extract revealed a potent activity against the Gram-positive bacteria with the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 62.5 MUg/ml. High activity against all the three Gram-positive bacteria was also observed for the extracts of Cratoxylum formosum ssp. pruniflorum, Pogostemon cablin, and Pedilanthus tithymaloides with MICs of 125, 125 and 250 MUg/ml and MBCs of 125 250, 125-250 and 250-500 MUg/ml, respectively. The extracts of C. formosum ssp. pruniflorum and P. tithymaloides showed a broad-spectrum antibacterial activity against all the bacteria tested with the MICs of 125-2,000 MUg/ml. CONCLUSION: This study indicates clear evidence supporting the traditional use of the plants in treating infectious diseases related to bacteria. In particular, these plant species showed moderate to high antibacterial activity against the Gram-positive bacteria tested. PMID- 26819219 TI - SAGES Assessment on the da Vinci Surgical System. PMID- 26819221 TI - Continuous particle separation using pressure-driven flow-induced miniaturizing free-flow electrophoresis (PDF-induced MU-FFE). AB - In this paper, we introduce pressure-driven flow-induced miniaturizing free-flow electrophoresis (PDF-induced MU-FFE), a novel continuous separation method. In our separation system, the external flow and electric field are applied to particles, such that particle movement is affected by pressure-driven flow, electroosmosis, and electrophoresis. We then analyzed the hydrodynamic drag force and electrophoretic force applied to the particles in opposite directions. Based on this analysis, micro- and nano-sized particles were separated according to their electrophoretic mobilities with high separation efficiency. Because the separation can be achieved in a simple T-shaped microchannel, without the use of internal electrodes, it offers the advantages of low-cost, simple device fabrication and bubble-free operation, compared with conventional MU-FFE methods. Therefore, we expect the proposed separation method to have a wide range of filtering/separation applications in biochemical analysis. PMID- 26819220 TI - Type I Interferon response in olfactory bulb, the site of tick-borne flavivirus accumulation, is primarily regulated by IPS-1. AB - BACKGROUND: Although type I interferons (IFNs)-key effectors of antiviral innate immunity are known to be induced via different pattern recognition receptors (PRRs), the cellular source and the relative contribution of different PRRs in host protection against viral infection is often unclear. IPS-1 is a downstream adaptor for retinoid-inducible gene I (RIG-I)-like receptor signaling. In this study, we investigate the relative contribution of IPS-1 in the innate immune response in the different brain regions during infection with tick-borne encephalitis virus (TBEV), a flavivirus that causes a variety of severe symptoms like hemorrhagic fevers, encephalitis, and meningitis in the human host. METHODS: IPS-1 knockout mice were infected with TBEV/Langat virus (LGTV), and viral burden in the peripheral and the central nervous systems, type I IFN induction, brain infiltrating cells, and inflammatory response was analyzed. RESULTS: We show that IPS-1 is indispensable for controlling TBEV and LGTV infections in the peripheral and central nervous system. Our data indicate that IPS-1 regulates neuropathogenicity in mice. IFN response is differentially regulated in distinct regions of the central nervous system (CNS) influencing viral tropism, as LGTV replication was mainly restricted to olfactory bulb in wild-type (WT) mice. In contrast to the other brain regions, IFN upregulation in the olfactory bulb was dependent on IPS-1 signaling. IPS-1 regulates basal levels of antiviral interferon-stimulated genes (ISGs) like viperin and IRF-1 which contributes to the establishment of early viral replication which inhibits STAT1 activation. This diminishes the antiviral response even in the presence of high IFN-beta levels. Consequently, the absence of IPS-1 causes uncontrolled virus replication, in turn resulting in apoptosis, activation of microglia and astrocytes, elevated proinflammatory response, and recruitment of inflammatory cells into the CNS. CONCLUSIONS: We show that LGTV replication is restricted to the olfactory bulb and that IPS-1 is a very important player in the olfactory bulb in shaping the innate immune response by inhibiting early viral replication and viral spread throughout the central nervous system. In the absence of IPS-1, higher viral replication leads to the evasion of antiviral response by inhibiting interferon signaling. Our data suggest that the local microenvironment of distinct brain regions is critical to determine virus permissiveness. PMID- 26819222 TI - Biological Mesh Implants for Abdominal Hernia Repair: US Food and Drug Administration Approval Process and Systematic Review of Its Efficacy. AB - IMPORTANCE: Expensive biological mesh materials are increasingly used to reinforce abdominal wall hernia repairs. The clinical and cost benefit of these materials are unknown. OBJECTIVES: To review the published evidence on the use of biological mesh materials and to examine the US Food and Drug Administration (FDA) approval history for these devices. EVIDENCE ACQUISITION: Search of multiple electronic databases (Ovid, MEDLINE, EMBASE, Cochrane Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, and Cochrane National Health Service Economic Evaluation Database) to identify articles published between 1948 and June 30, 2015, on the use of biological mesh materials used to reinforce abdominal wall hernia repair. Keywords searched included surgical mesh, abdominal hernia, recurrence, infection, fistula, bioprosthesis, biocompatible materials, absorbable implants, dermis, and collagen. The FDA online database for 510(k) clearances was reviewed for all commercially available biological mesh materials. The median national price for mesh materials was established by a benchmarking query through several Integrated Delivery Network and Group Purchasing Organization tools. EVIDENCE SYNTHESIS: Of 274 screened articles, 20 met the search criteria. Most were case series that reported results of convenience samples of patients at single institutions with a variety of clinical problems. Only 3 of the 20 were comparative studies. There were no randomized clinical trials. In total, outcomes for 1033 patients were described. Studies varied widely in follow-up time, operative technique, meshes used, and patient selection criteria. Reported outcomes and clinical outcomes, such as fistula formation and infection, were inconsistently reported across studies. Conflicts of interest were not reported in 16 of the 20 studies. Recurrence rates ranged from 0% to 80%. All biological mesh devices were approved by the FDA based on substantial equivalence to a group of nonbiological predicate devices that, on average, were one-third less costly. CONCLUSIONS AND RELEVANCE: There is insufficient evidence to determine the extra costs associated with or the clinical efficacy of biological mesh materials for the repair of abdominal wall hernia. PMID- 26819223 TI - Nonlinear dynamics induced anomalous Hall effect in topological insulators. AB - We uncover an alternative mechanism for anomalous Hall effect. In particular, we investigate the magnetisation dynamics of an insulating ferromagnet (FM) deposited on the surface of a three-dimensional topological insulator (TI), subject to an external voltage. The spin-polarised current on the TI surface induces a spin-transfer torque on the magnetisation of the top FM while its dynamics can change the transmission probability of the surface electrons through the exchange coupling and hence the current. We find a host of nonlinear dynamical behaviors including multistability, chaos, and phase synchronisation. Strikingly, a dynamics mediated Hall-like current can arise, which exhibits a nontrivial dependence on the channel conductance. We develop a physical understanding of the mechanism that leads to the anomalous Hall effect. The nonlinear dynamical origin of the effect stipulates that a rich variety of final states exist, implying that the associated Hall current can be controlled to yield desirable behaviors. The phenomenon can find applications in Dirac-material based spintronics. PMID- 26819224 TI - An unusual cause of syncope while gardening. PMID- 26819225 TI - Detection and prognostic value of pulmonary congestion by lung ultrasound in ambulatory heart failure patients. AB - AIMS: Pulmonary congestion is a common and important finding in heart failure (HF). While clinical examination and chest radiography are insensitive, lung ultrasound (LUS) is a novel technique that may detect and quantify subclinical pulmonary congestion. We sought to independently relate LUS and clinical findings to 6-month HF hospitalizations and all-cause mortality (composite primary outcome). METHODS: We used LUS to examine 195 NYHA class II-IV HF patients (median age 66, 61% men, 74% white, ejection fraction 34%) during routine cardiology outpatient visits. Lung ultrasound was performed in eight chest zones with a pocket ultrasound device (median exam duration 2 min) and analysed offline. RESULTS: In 185 patients with adequate LUS images in all zones, the sum of B-lines (vertical lines on LUS) ranged from 0 to 13. B-lines, analysed by tertiles, were associated with clinical and laboratory markers of congestion. Thirty-two per cent of patients demonstrated >=3 B-lines on LUS, yet 81% of these patients had no findings on auscultation. During the follow-up period, 50 patients (27%) were hospitalized for HF or died. Patients in the third tertile (>=3 B-lines) had a four-fold higher risk of the primary outcome (adjusted HR 4.08, 95% confidence interval, CI 1.95, 8.54; P < 0.001) compared with those in the first tertile and spent a significantly lower number of days alive and out of the hospital (125 days vs. 165 days; adjusted P < 0.001). CONCLUSIONS: Pulmonary congestion assessed by ultrasound is prevalent in ambulatory patients with chronic HF, is associated with other features of clinical congestion, and identifies those who have worse prognosis. PMID- 26819226 TI - TAVI or No TAVI: identifying patients unlikely to benefit from transcatheter aortic valve implantation. AB - Transcatheter aortic valve implantation (TAVI) has spawned the evolution of novel catheter-based therapies for a variety of cardiovascular conditions. Newer device iterations are delivering lower peri- and early post-procedural complication rates in patients with aortic stenosis, who were otherwise deemed too high risk for conventional surgical valve replacement. Yet beyond the post-procedural period, a considerable portion of current TAVI recipients fail to derive a benefit from TAVI, either dying or displaying a lack of clinical and functional improvement. Considerable interest now lies in better identifying factors likely to predict futility post-TAVI. Implicit in this are the critical roles of frailty, disability, and a multimorbidity patient assessment. In this review, we outline the roles that a variety of medical comorbidities play in determining futile post-TAVI outcomes, including the critical role of frailty underlying the identification of patients unlikely to benefit from TAVI. We discuss various TAVI risk scores, and further propose that by combining such scores along with frailty parameters and the presence of specific organ failure, a more accurate and holistic assessment of potential TAVI-related futility could be achieved. PMID- 26819227 TI - Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME(r) trial. AB - AIMS: We previously reported that in the EMPA-REG OUTCOME((r)) trial, empagliflozin added to standard of care reduced the risk of 3-point major adverse cardiovascular events, cardiovascular and all-cause death, and hospitalization for heart failure in patients with type 2 diabetes and high cardiovascular risk. We have now further investigated heart failure outcomes in all patients and in subgroups, including patients with or without baseline heart failure. METHODS AND RESULTS: Patients were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo. Seven thousand and twenty patients were treated; 706 (10.1%) had heart failure at baseline. Heart failure hospitalization or cardiovascular death occurred in a significantly lower percentage of patients treated with empagliflozin [265/4687 patients (5.7%)] than with placebo [198/2333 patients (8.5%)] [hazard ratio, HR: 0.66 (95% confidence interval: 0.55-0.79); P < 0.001], corresponding to a number needed to treat to prevent one heart failure hospitalization or cardiovascular death of 35 over 3 years. Consistent effects of empagliflozin were observed across subgroups defined by baseline characteristics, including patients with vs. without heart failure, and across categories of medications to treat diabetes and/or heart failure. Empagliflozin improved other heart failure outcomes, including hospitalization for or death from heart failure [2.8 vs. 4.5%; HR: 0.61 (0.47-0.79); P < 0.001] and was associated with a reduction in all-cause hospitalization [36.8 vs. 39.6%; HR: 0.89 (0.82-0.96); P = 0.003]. Serious adverse events and adverse events leading to discontinuation were reported by a higher proportion of patients with vs. without heart failure at baseline in both treatment groups, but were no more common with empagliflozin than with placebo. CONCLUSION: In patients with type 2 diabetes and high cardiovascular risk, empagliflozin reduced heart failure hospitalization and cardiovascular death, with a consistent benefit in patients with and without baseline heart failure. PMID- 26819228 TI - Thionin-like peptide from Capsicum annuum fruits: mechanism of action and synergism with fluconazole against Candida species. AB - BACKGROUND: Thionins are a family of plant antimicrobial peptides (AMPs), which participate in plant defense system against pathogens. Here we describe some aspects of the CaThi thionin-like action mechanism, previously isolated from Capsicum annuum fruits. Thionin-like peptide was submitted to antimicrobial activity assays against Candida species for IC50 determination and synergism with fluconazole evaluation. Viability and plasma membrane permeabilization assays, induction of intracellular ROS production analysis and CaThi localization in yeast cells were also investigated. RESULTS: CaThi had strong antimicrobial activity against six tested pathogenic Candida species, with IC50 ranging from 10 to 40 MUg.mL(-1). CaThi antimicrobial activity on Candida species was candidacidal. Moreover, CaThi caused plasma membrane permeabilization in all yeasts tested and induces oxidative stresses only in Candida tropicalis. CaThi was intracellularly localized in C. albicans and C. tropicalis, however localized in nuclei in C. tropicalis, suggesting a possible nuclear target. CaThi performed synergistically with fluconazole inhibiting all tested yeasts, reaching 100% inhibition in C. parapsilosis. The inhibiting concentrations for the synergic pair ranged from 1.3 to 4.0 times below CaThi IC50 and from zero to 2.0 times below fluconazole IC50. CONCLUSION: The results reported herein may ultimately contribute to future efforts aiming to employ this plant-derived AMP as a new therapeutic substance against yeasts. PMID- 26819229 TI - The SAME-TT2R2 score predicts the quality of anticoagulation control in patients with acute VTE. A real-life inception cohort study. AB - The SAMe-TT2R2 score has recently been proposed to predict the quality of vitamin K antagonist (VKA) anticoagulation control in patients with atrial fibrillation. We aimed at investigating whether the score is effective also in patients with venous thromboembolism (VTE). Patients included in the START-Register because started VKA therapy for a recent VTE episode and with > 3 months follow-up were analyzed. The score was calculated using the baseline patient's characteristics present in the electronic database of the registry, where all INR results were also available and analysed to calculate the time in therapeutic range (TTR). A total of 1308 patients (53.4 % female, median age 68 years) were analysed. During 998 patient-years follow-up, the median TTR was 63 %. The maximum score in the patients was 4, with 70 % of them having 0-1. INR controls within range (2.0-3.0) were significantly less prevalent in patients with score >= 2 vs 0-1 score (58.5 +/- 20 % vs 61.5 +/- 19 %, respectively, p = 0.046). Patients with score >= 2 vs 0-1 had a highly significant lower TTR during the first 3 months of therapy (53 +/- 26 % and 61 +/- 26 %, respectively; p=0.0001), difference mainly due to more time spent below 2.0 INR (38 +/- 28 % vs 31.3 +/- 26.7 %, respectively; p=0.0001). In conclusion, the study proved, for the first time, that the SAMe TT2R2 score is useful to predict among VTE patients those who will have good (score 0-1) or less good (score >= 2) VKA anticoagulation control. The score can help decision-making in everyday clinical practice, especially when choosing between VKA and non-vitamin K antagonists direct anticoagulants. PMID- 26819230 TI - Acute transverse colon volvulus with secondary gastric isquemia. Case report. AB - Acute colonic volvulus accounts for 10% of all intestinal obstructions being the transverse colon volvulus an exceptional localization (2-4%). Late diagnosis is made as there are no pathognomonic clinical or radiological findings for this pathology. We present the case of an 81 year-old male with acute transverse colon volvulus that involved the gastric antrum causing irreversible ischemia. Subtotal gastrectomy, subtotal colectomy and reconstruction with Y en Roux gastrojejunostomy and ileosigmoid anastomosis was performed given the good overall status of the patient. Decompressive colonoscopy is not advised given the high probability of ischemic lesions in these cases; surgical exploration is mandatory in these circumstances. Surgical detortion with or without colopexia carries important recurrence rates. Treatment of choice includes colectomy with or without primary anastomosis. There are no reports on gastric ischemic necrosis in the setting of a transverse colon volvulus making this case unusual and unique. PMID- 26819231 TI - Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports. AB - OBJECTIVE: To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.Design Systematic review and meta analysis. MAIN OUTCOME MEASURES: Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia. DATA SOURCES: Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly's website. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms. DATA EXTRACTION AND ANALYSIS: Two researchers extracted data independently; the outcomes were meta-analysed by Peto's exact method (fixed effect model). RESULTS: We included 70 trials (64,381 pages of clinical study reports) with 18,526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly's website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was incomplete. CONCLUSIONS: Because of the shortcomings identified and having only partial access to appendices with no access to case report forms, the harms could not be estimated accurately. In adults there was no significant increase in all four outcomes, but in children and adolescents the risk of suicidality and aggression doubled. To elucidate the harms reliably, access to anonymised individual patient data is needed. PMID- 26819232 TI - Blood Loss and Transfusion Requirements in Metastatic Spinal Tumor Surgery: Evaluation of Influencing Factors. AB - BACKGROUND: Metastatic spine tumor surgery (MSTS) can be associated with significant blood loss. Previous studies did not provide comprehensive data on blood loss in MSTS. Thorough study elaborating the blood loss, transfusion requirement, and their influencing factors is required. This study aimed to investigate the estimated blood loss and transfusion requirements associated with various surgical approaches and surgically managed vertebral levels for spinal metastases from different primary tumors. METHODS: The study retrospectively evaluated 243 patients who underwent surgery for metastatic spine tumors at the authors' institution between 2005 and 2014. Estimated intraoperative blood loss and transfusion requirement were assessed for different primary tumors including lung, breast, prostate, gastrointestinal, renal, liver, thyroid, myeloma/lymphoma, and others; types of surgical procedure (cervical corpectomy +/ stabilization, thoracolumbar posterior decompression +/- instrumentation, thoracolumbar corpectomy, minimally invasive surgery); and levels of instrumentation and decompression. Multivariate linear regression was attempted to investigate the factors influencing blood loss and transfusion requirements. RESULTS: The mean blood loss was 870 +/- 720 ml, and the average blood transfusion was 1.5 +/- 1.9 U. The mean blood loss was 1103 ml for patients who received blood transfusion and 597 ml for those who did not. Multivariate analysis showed that the significant factors influencing blood loss were primary tumor, type of surgery, and prolonged operative time. The influencing factors for blood transfusion were primary tumor, type of surgery, preoperative hemoglobin, and prolonged operative time. CONCLUSIONS: Significant variations in blood loss and transfusion requirement were based on primary tumor of spinal metastases, surgical approaches, and operative time. These findings will help clinicians in preoperative planning to address the problem of blood loss during MSTS. PMID- 26819234 TI - Almanac 2015: coronary artery disease. AB - Recent years have seen major advances in the evaluation and treatment of patients with coronary artery disease. These include assessment of novel biomarkers and imaging methods for patients at risk for coronary artery disease, care of patients with ST-segment elevation myocardial infarction, a novel device to treat medical refractory angina, use of non-statin lipid-lowering agents, a better understanding of the risks and benefits of long-term dual antiplatelet therapy and the use of the newer antiplatelet agents. This article summarises research related to coronary artery disease published in Heart in 2014 and 2015, within the context of other major cardiovascular journals. PMID- 26819233 TI - Simulation and qualitative analysis of glucose variability, mean glucose, and hypoglycemia after subcutaneous insulin therapy for stress hyperglycemia. AB - BACKGROUND: The critically ill can have persistent dysglycemia during the "subacute" recovery phase of their illness because of altered gene expression; it is also not uncommon for these patients to receive continuous enteral nutrition during this time. The optimal short-acting subcutaneous insulin therapy that should be used in this clinical scenario, however, is unknown. Our aim was to conduct a qualitative numerical study of the glucose-insulin dynamics within this patient population to answer the above question. This analysis may help clinicians design a relevant clinical trial. METHODS: Eight virtual patients with stress hyperglycemia were simulated by means of a mathematical model. Each virtual patient had a different combination of insulin resistance and insulin deficiency that defined their unique stress hyperglycemia state; the rate of gluconeogenesis was also doubled. The patients received 25 injections of subcutaneous regular or Lispro insulin (0-6 U) with 3 rates of continuous nutrition. The main outcome measurements were the change in mean glucose concentration, the change in glucose variability, and hypoglycemic episodes. These end points were interpreted by how the ultradian oscillations of glucose concentration were affected by each insulin preparation. RESULTS: Subcutaneous regular insulin lowered both mean glucose concentrations and glucose variability in a linear fashion. No hypoglycemic episodes were noted. Although subcutaneous Lispro insulin lowered mean glucose concentrations, glucose variability increased in a nonlinear fashion. In patients with high insulin resistance and nutrition at goal, "rebound hyperglycemia" was noted after the insulin analog was rapidly metabolized. When the nutritional source was removed, hypoglycemia tended to occur at higher Lispro insulin doses. Finally, patients with severe insulin resistance seemed the most sensitive to insulin concentration changes. CONCLUSIONS: Subcutaneous regular insulin consistently lowered mean glucose concentrations and glucose variability; its linear dose-response curve rendered the preparation better suited for a sliding-scale protocol. The longer duration of action of subcutaneous regular insulin resulted in better glycemic-control metrics for patients who were continuously postprandial. Clinical trials are needed to examine whether these numerical results represent the glucose-insulin dynamics that occur in intensive care units; if present, their clinical effects should be evaluated. PMID- 26819235 TI - Graphics and statistics for cardiology: comparing categorical and continuous variables. AB - Graphs are a standard tool for succinctly describing data, and play a crucial role supporting statistical analyses of that data. However, all too often, graphical display of data in submitted manuscripts is either inappropriate for the task at hand or poorly executed, requiring revision prior to publication. To assist authors, in this paper, we present several forms of graph, for data typically seen in Heart, including dot charts, violin plots, histograms and boxplots for quantitative data, and mosaic plots and bar charts for categorical data. Justification for using these specific plots is drawn from the literature on visual perception; we also provide software instruction and examples, using various popular packages. PMID- 26819236 TI - Mental Health among displaced Syrians: findings from the Syria Public Health Network. PMID- 26819237 TI - Public health, politics and the stigma of mass hysteria: lessons from an outbreak of unusual illness. PMID- 26819238 TI - Community structure, seasonal variations and interactions between native and invasive cattle tick species in Benin and Burkina Faso. AB - BACKGROUND: The variation of tick abundance on ruminants had received little attention in West Africa before Rhipicephalus (Boophilus) microplus started to invade this region in the early 2000s. Ten years later, R. microplus was suspected to have replaced the native ticks. In addition to testing this hypothesis, this study investigated the interactions between native and invasive ticks and the relative role of climatic and geographical variables in the variations of tick community composition (beta diversity) on cattle herds. METHODS: A one-year-long survey was performed in Benin and Burkina Faso during which adult ticks were collected from 144 steers from 12 localities in four different areas once a month. Morphological features were used to assign the collected ticks to different species (A. variegatum, R. annulatus, R. decoloratus, R. microplus and R. geigyi). Beta diversity analyses and generalized linear models allowed characterizing the geographical variations in species assemblage and the effect of co-infestation patterns on the seasonal variations in the abundance and incidence rates of each taxon. RESULTS: About 68% (22,491/32,148) of all the adult ticks collected in one year were R. microplus. The most heterogeneously distributed taxa were Hyalomma spp and R. microplus and the lowest specific diversity was found in Central Burkina Faso. Although climatic variables did not provide any additional information on the variation in species assemblages compared with the sampling geography, adult tick abundance tended to peak during the late (Boophilus subgenus) or early (other taxa) rainy season. In most taxon-per-locality analyses, the abundance and incidence rate of a given tick taxon significantly increased when the host was co-infested by other taxa. The comparison with previous estimates (when possible) did not support the hypothesis that R. microplus invasion led to a decrease in native tick species abundance. CONCLUSIONS: The co-infestation patterns among native and invasive tick species are key factors for the determination of the community structure and the infestation dynamics of each tick taxon in West African cattle. PMID- 26819239 TI - Engineering ionic liquid-tolerant cellulases for biofuels production. AB - Dissolution of lignocellulosic biomass in certain ionic liquids (ILs) can provide an effective pretreatment prior to enzymatic saccharification of cellulose for biofuels production. Toward the goal of combining pretreatment and enzymatic hydrolysis, we evolved enzyme variants of Talaromyces emersonii Cel7A to be more active and stable than wild-type T. emersonii Cel7A or Trichoderma reesei Cel7A in aqueous-IL solutions (up to 43% (w/w) 1,3-dimethylimdazolium dimethylphosphate and 20% (w/w) 1-ethyl-3-methylimidazolium acetate). In general, greater enzyme stability in buffer at elevated temperature corresponded to greater stability in aqueous-ILs. Post-translational modification of the N-terminal glutamine residue to pyroglutamate via glutaminyl cyclase enhanced the stability of T. emersonii Cel7A and variants. Differential scanning calorimetry revealed an increase in melting temperature of 1.9-3.9 degrees C for the variant 1M10 over the wild-type T. emersonii Cel7A in aqueous buffer and in an IL-aqueous mixture. We observed this increase both with and without glutaminyl cyclase treatment of the enzymes. PMID- 26819240 TI - Overcoming a species-specificity barrier in development of an inhibitory antibody targeting a modulator of tumor stroma. AB - The secreted disulfide catalyst Quiescin sulfhydryl oxidase-1 (QSOX1) affects extracellular matrix organization and is overexpressed in various adenocarcinomas and associated stroma. Inhibition of extracellular human QSOX1 by a monoclonal antibody decreased tumor cell migration in a cell co-culture model and hence may have therapeutic potential. However, the species specificity of the QSOX1 monoclonal antibody has been a setback in assessing its utility as an anti metastatic agent in vivo, a common problem in the antibody therapy industry. We therefore used structurally guided engineering to expand the antibody species specificity, improving its affinity toward mouse QSOX1 by at least four orders of magnitude. A crystal structure of the re-engineered variant, complexed with its mouse antigen, revealed that the antibody accomplishes dual-species targeting through altered contacts between its heavy and light chains, plus replacement of bulky aromatics by flexible side chains and versatile water-bridged polar interactions. In parallel, we produced a surrogate antibody targeting mouse QSOX1 that exhibits a new QSOX1 inhibition mode. This set of three QSOX1 inhibitory antibodies is compatible with various mouse models for pre-clinical trials and biotechnological applications. In this study we provide insights into structural blocks to cross-reactivity and set up guideposts for successful antibody design and re-engineering. PMID- 26819241 TI - Mapping the genomic architecture of adaptive traits with interspecific introgressive origin: a coalescent-based approach. AB - Recent studies of eukaryotes including human and Neandertal, mice, and butterflies have highlighted the major role that interspecific introgression has played in adaptive trait evolution. A common question arises in each case: what is the genomic architecture of the introgressed traits? One common approach that can be used to address this question is association mapping, which looks for genotypic markers that have significant statistical association with a trait. It is well understood that sample relatedness can be a confounding factor in association mapping studies if not properly accounted for. Introgression and other evolutionary processes (e.g., incomplete lineage sorting) typically introduce variation among local genealogies, which can also differ from global sample structure measured across all genomic loci. In contrast, state-of-the-art association mapping methods assume fixed sample relatedness across the genome, which can lead to spurious inference. We therefore propose a new association mapping method called Coal-Map, which uses coalescent-based models to capture local genealogical variation alongside global sample structure. Using simulated and empirical data reflecting a range of evolutionary scenarios, we compare the performance of Coal-Map against EIGENSTRAT, a leading association mapping method in terms of its popularity, power, and type I error control. Our empirical data makes use of hundreds of mouse genomes for which adaptive interspecific introgression has recently been described. We found that Coal-Map's performance is comparable or better than EIGENSTRAT in terms of statistical power and false positive rate. Coal-Map's performance advantage was greatest on model conditions that most closely resembled empirically observed scenarios of adaptive introgression. These conditions had: (1) causal SNPs contained in one or a few introgressed genomic loci and (2) varying rates of gene flow - from high rates to very low rates where incomplete lineage sorting dominated as a primary cause of local genealogical variation. PMID- 26819242 TI - The impact of a community driven mass media campaign on the utilisation of maternal health care services in rural Malawi. AB - BACKGROUND: Mass media is critical in disseminating public health information, improving health knowledge and changing health behaviours. However, most of the mass media public health interventions do not sufficiently engage the local people; they are externally determined. Due to this, very little is known about the effects of locally instigated mass media promotion. Therefore, the aim of this study was to examine the impact of a community driven mass media campaign called Phukusi la Moyo (tips of life) on the utilisation of maternal health care services. METHODS: A community-based cross-sectional study involving 3825 women of reproductive age (15-49 years) was conducted in rural Malawi to evaluate the Phukusi la Moyo (PLM) campaign. To do this, we compared the utilisation of maternal health care services between women who were exposed to the PLM campaign and those who were not. Respondents were identified using a multistage cluster sampling method. This involved systematically selecting communities (clusters), households and respondents. Associations were examined using Pearson chi square test and a multivariable logistic regression model. RESULTS: The likelihood of using contraceptives (AOR = 1.61; 95% CI = 1.32-1.96), sleeping under mosquito bed-nets (AOR = 1.65; 95% CI = 1.39-1.97), utilising antenatal care services (AOR = 2.62; 95% CI = 1.45-4.73) and utilising postnatal care services (AOR = 1.59; CI = 1.29-1.95) were significantly higher among women who had exposure to the PLM campaign than those who did not. No significant association was found between health facility delivery and exposure to the PLM campaign. CONCLUSION: Women exposed to a community driven mass media campaign in rural Malawi were more likely to utilise maternal health care services than their unexposed counterparts. Since, the use of maternal health care services reduces the risk of maternal morbidity and mortality, community-led mass media could play a significant role towards improving maternal health outcomes in low-and-middle income countries. Therefore, we recommend the use of locally driven mass media in disseminating public health information in limited resource settings. PMID- 26819243 TI - SOHSite: incorporating evolutionary information and physicochemical properties to identify protein S-sulfenylation sites. AB - BACKGROUND: Protein S-sulfenylation is a type of post-translational modification (PTM) involving the covalent binding of a hydroxyl group to the thiol of a cysteine amino acid. Recent evidence has shown the importance of S-sulfenylation in various biological processes, including transcriptional regulation, apoptosis and cytokine signaling. Determining the specific sites of S-sulfenylation is fundamental to understanding the structures and functions of S-sulfenylated proteins. However, the current lack of reliable tools often limits researchers to use expensive and time-consuming laboratory techniques for the identification of S-sulfenylation sites. Thus, we were motivated to develop a bioinformatics method for investigating S-sulfenylation sites based on amino acid compositions and physicochemical properties. RESULTS: In this work, physicochemical properties were utilized not only to identify S-sulfenylation sites from 1,096 experimentally verified S-sulfenylated proteins, but also to compare the effectiveness of prediction with other characteristics such as amino acid composition (AAC), amino acid pair composition (AAPC), solvent-accessible surface area (ASA), amino acid substitution matrix (BLOSUM62), position-specific scoring matrix (PSSM), and positional weighted matrix (PWM). Various prediction models were built using support vector machine (SVM) and evaluated by five-fold cross validation. The model constructed from hybrid features, including PSSM and physicochemical properties, yielded the best performance with sensitivity, specificity, accuracy and MCC measurements of 0.746, 0.737, 0.738 and 0.337, respectively. The selected model also provided a promising accuracy (0.693) on an independent testing dataset. Additionally, we employed TwoSampleLogo to help discover the difference of amino acid composition among S-sulfenylation, S glutathionylation and S-nitrosylation sites. CONCLUSION: This work proposed a computational method to explore informative features and functions for protein S sulfenylation. Evaluation by five-fold cross validation indicated that the selected features were effective in the identification of S-sulfenylation sites. Moreover, the independent testing results demonstrated that the proposed method could provide a feasible means for conducting preliminary analyses of protein S sulfenylation. We also anticipate that the uncovered differences in amino acid composition may facilitate future studies of the extensive crosstalk among S sulfenylation, S-glutathionylation and S-nitrosylation. PMID- 26819244 TI - Medical Decisions of Pediatric Residents Turn Riskier after a 24-Hour Call with No Sleep. AB - BACKGROUND: Despite a gradual reduction in the workload during residency, 24-hour calls are still an integral part of most training programs. While sleep deprivation increases the risk propensity, the impact on medical risk taking has not been studied. OBJECTIVE: This study aimed to assess the clinical decision making and psychomotor performance of pediatric residents following a limited nap time during a 24-hour call. METHODS: A neurocognitive battery (IntegNeuro) and a medical decision questionnaire were completed by 44 pediatric residents at 2 time points: after a 24-hour call and following 3 nights with no calls (sleep >=5 hours). To monitor sleep, residents wore actigraphs and completed sleep logs. RESULTS: Nap time during the shift was <1 hour in 14 cases (32%), 1 to 2 hours in 16 cases (35%), and 2 to 3 hours in 14 cases (32%). Residents who napped less than 1 hour chose the riskier medical option in 50% of cases compared with 36% when answering the same questionnaire after 3 nights with no calls (P = 0.002). This effect was not found in residents who napped 1 to 2 hours (no change in risk taking) or 2 to 3 hours (4% decreased risk taking) (difference between groups, P = 0.001). Risk-taking tendency inversely correlated with sustained attention scores (Pearson = -0.433, P = 0.003). Sustained attention was the neurocognitive domain most affected by sleep deprivation (effect size = 0.29, P = 0.025). CONCLUSIONS: This study suggests that residents napping less than an hour during a night shift are prone to riskier clinical decisions. Hence, enabling residents to nap at least 1 hour during shifts is recommended. PMID- 26819246 TI - Collective Fluctuations in the Dynamics of Adaptation and Other Traveling Waves. AB - The dynamics of adaptation are difficult to predict because it is highly stochastic even in large populations. The uncertainty emerges from random genetic drift arising in a vanguard of particularly fit individuals of the population. Several approaches have been developed to analyze the crucial role of genetic drift on the expected dynamics of adaptation, including the mean fitness of the entire population, or the fate of newly arising beneficial deleterious mutations. However, little is known about how genetic drift causes fluctuations to emerge on the population level, where it becomes palpable as variations in the adaptation speed and the fitness distribution. Yet these phenomena control the decay of genetic diversity and variability in evolution experiments and are key to a truly predictive understanding of evolutionary processes. Here, we show that correlations induced by these emergent fluctuations can be computed at any arbitrary order by a suitable choice of a dynamical constraint. The resulting linear equations exhibit fluctuation-induced terms that amplify short-distance correlations and suppress long-distance ones. These terms, which are in general not small, control the decay of genetic diversity and, for wave-tip dominated ("pulled") waves, lead to anticorrelations between the tip of the wave and the lagging bulk of the population. While it is natural to consider the process of adaptation as a branching random walk in fitness space subject to a constraint (due to finite resources), we show that other traveling wave phenomena in ecology and evolution likewise fall into this class of constrained branching random walks. Our methods, therefore, provide a systematic approach toward analyzing fluctuations in a wide range of population biological processes, such as adaptation, genetic meltdown, species invasions, or epidemics. PMID- 26819245 TI - Segregation of Naturally Occurring Mitochondrial DNA Variants in a Mini-Pig Model. AB - The maternally inherited mitochondrial genome (mtDNA) is present in multimeric form within cells and harbors sequence variants (heteroplasmy). While a single mtDNA variant at high load can cause disease, naturally occurring variants likely persist at low levels across generations of healthy populations. To determine how naturally occurring variants are segregated and transmitted, we generated a mini pig model, which originates from the same maternal ancestor. Following next generation sequencing, we identified a series of low-level mtDNA variants in blood samples from the female founder and her daughters. Four variants, ranging from 3% to 20%, were selected for validation by high-resolution melting analysis in 12 tissues from 31 animals across three generations. All four variants were maintained in the offspring, but variant load fluctuated significantly across the generations in several tissues, with sex-specific differences in heart and liver. Moreover, variant load was persistently reduced in high-respiratory organs (heart, brain, diaphragm, and muscle), which correlated significantly with higher mtDNA copy number. However, oocytes showed increased heterogeneity in variant load, which correlated with increased mtDNA copy number during in vitro maturation. Altogether, these outcomes show that naturally occurring mtDNA variants segregate and are maintained in a tissue-specific manner across generations. This segregation likely involves the maintenance of selective mtDNA variants during organogenesis, which can be differentially regulated in oocytes and preimplantation embryos during maturation. PMID- 26819248 TI - Cardiac Autonomic Dysfunction: Particulate Air Pollution Effects Are Modulated by Epigenetic Immunoregulation of Toll-like Receptor 2 and Dietary Flavonoid Intake. PMID- 26819247 TI - Prescriptions for hydrocodone plummet after US tightens prescribing rules. PMID- 26819249 TI - Impact of Nonoptimal Intakes of Saturated, Polyunsaturated, and Trans Fat on Global Burdens of Coronary Heart Disease. PMID- 26819251 TI - Overcoming Challenges With Statin Therapy. PMID- 26819252 TI - Forced Expiratory Volume in the First Second and Aldosterone as Mediators of Smoking Effect on Stroke in African Americans: The Jackson Heart Study. AB - BACKGROUND: Cigarette smoking is a risk factor for stroke, but the mechanisms by which smoking contributes to stroke are not well understood. This study aimed to evaluate the roles of lung function (represented by forced expiratory volume in the first second (FEV1)) and aldosterone as potential mediators of the association of smoking with stroke. METHODS AND RESULTS: The data were derived from 5010 Jackson Heart Study participants who had mean follow-up of 97.9 months. Using the Cox proportional hazards model, we estimated the hazard ratios of smoking for total stroke with and without adjustment for FEV1 and/or aldosterone at baseline after controlling for the confounders. The hazard ratio for current smoking (versus never smoking) was 2.70 (95% CI 1.71 to 4.25) for total stroke after adjustment for the confounders. Additional adjustment for FEV1 and aldosterone reduced the hazard ratio to 2.32 (95% CI 1.42 to 3.79), suggesting that 22.4% of the excess risk of current smoking for total stroke is mediated by these factors. FEV1 and aldosterone account for 13.1% and 12.1%, respectively, of the excess risk. The hazard ratio for FEV1 increased (0.61 versus 0.65) after including systemic inflammatory marker C-reactive protein, and the hazard ratios for aldosterone were comparable for the models that included all confounders and smoking status with or without different blood pressure measurements. CONCLUSIONS: Our findings suggest that the difference in stroke risk between current and never smokers may develop partially through pathways involving lung function and aldosterone and that the mediation effect through aldosterone is independent of blood pressure. PMID- 26819254 TI - A Simple Method for Labeling Human Embryonic Stem Cells Destined to Lose Undifferentiated Potency. AB - Mitochondrial oxidative phosphorylation is a major source of cellular ATP. Its usage as an energy source varies, not only according to the extracellular environment, but also during development and differentiation, as indicated by the reported changes in the flux ratio of glycolysis to oxidative phosphorylation during embryonic stem (ES) cell differentiation. The fluorescent probe JC-1 allows visualization of changes in the mitochondrial membrane potential produced by oxidative phosphorylation. Strong JC-1 signals were localized in the differentiated cells located at the edge of H9 ES colonies that expressed vimentin, an early differentiation maker. The JC-1 signals were further intensified when individual adjacent colonies were in contact with each other. Time-lapse analyses revealed that JC-1-labeled H9 cells under an overconfluent condition were highly differentiated after subculture, suggesting that monitoring oxidative phosphorylation in live cells might facilitate the prediction of induced pluripotent stem cells, as well as ES cells, that are destined to lose their undifferentiated potency. PMID- 26819253 TI - Soluble Tumor Necrosis Factor Receptor 1 Released by Skin-Derived Mesenchymal Stem Cells Is Critical for Inhibiting Th17 Cell Differentiation. AB - T helper 17 (Th17) cells play an important role in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Th17 cell differentiation from naive T cells can be induced in vitro by the cytokines transforming growth factor beta1 and interleukin-6. However, it remains unclear whether other regulatory factors control the differentiation of Th17 cells. Mesenchymal stem cells (MSCs) have emerged as a promising candidate for inhibiting Th17 cell differentiation and autoimmune diseases. Despite the fact that several molecules have been linked to the immunomodulatory function of MSCs, many other key MSC-secreted regulators that are involved in inhibiting Th17 cell polarization are ill-defined. In this study, we demonstrated that the intraperitoneal administration of skin-derived MSCs (S-MSCs) substantially ameliorated the development of EAE in mice. We found that the proinflammatory cytokine tumor necrosis factor (TNF)-alpha, a key mediator in the pathophysiology of MS and EAE, was capable of promoting Th17 cell differentiation. Moreover, under inflammatory conditions, we demonstrated that S-MSCs produced high amounts of soluble TNF receptor 1 (sTNFR1), which binds TNF-alpha and antagonizes its function. Knockdown of sTNFR1 in S-MSCs decreased their inhibitory effect on Th17 cell differentiation ex vivo and in vivo. Thus, our data identified sTNFR1 and its target TNF-alpha as critical regulators for Th17 cell differentiation, suggesting a previously unrecognized mechanism for MSC therapy in Th17-mediated autoimmune diseases. PMID- 26819255 TI - Functional Differences Between Placental Micro- and Macrovascular Endothelial Colony-Forming Cells. AB - Alterations in the development of the placental vasculature can lead to pregnancy complications, such as preeclampsia. Currently, the cause of preeclampsia is unknown, and there are no specific prevention or treatment strategies. Further insight into the placental vasculature may aid in identifying causal factors. Endothelial colony-forming cells (ECFCs) are a subset of endothelial progenitor cells capable of self-renewal and de novo vessel formation in vitro. We hypothesized that ECFCs exist in the micro- and macrovasculature of the normal, term human placenta. Human placentas were collected from term pregnancies delivered by cesarean section (n = 16). Placental micro- and macrovasculature was collected from the maternal and fetal side of the placenta, respectively, and ECFCs were isolated and characterized. ECFCs were CD31(+), CD105(+), CD144(+), CD146(+), CD14(-), and CD45(-), took up 1,1'-dioctadecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate-labeled acetylated low-density lipoprotein, and bound Ulex europaeus agglutinin 1. In vitro, macrovascular ECFCs had a greater potential to generate high-proliferative colonies and formed more complex capillary-like networks on Matrigel compared with microvascular ECFCs. In contrast, in vivo assessment demonstrated that microvascular ECFCs had a greater potential to form vessels. Macrovascular ECFCs were of fetal origin, whereas microvascular ECFCs were of maternal origin. ECFCs exist in the micro- and macrovasculature of the normal, term human placenta. Although macrovascular ECFCs demonstrated greater vessel and colony-forming potency in vitro, this did not translate in vivo, where microvascular ECFCs exhibited a greater vessel-forming ability. These important findings contribute to the current understanding of normal placental vascular development and may aid in identifying factors involved in preeclampsia and other pregnancy complications. PMID- 26819257 TI - Maximal stomatal conductance to water and plasticity in stomatal traits differ between native and invasive introduced lineages of Phragmites australis in North America. AB - The fitness costs of reproduction by clonal growth can include a limited ability to adapt to environmental and temporal heterogeneity. Paradoxically, some facultatively clonal species are not only able to survive, but colonize, thrive and expand in heterogeneous environments. This is likely due to the capacity for acclimation (sensu stricto) that compensates for the fitness costs and complements the ecological advantages of clonality. Introduced Phragmites australis demonstrates great phenotypic plasticity in response to temperature, nutrient availability, geographic gradient, water depths, habitat fertility, atmospheric CO2, interspecific competition and intraspecific competition for light. However, no in situ comparative subspecies studies have explored the difference in plasticity between the non-invasive native lineage and the highly invasive introduced lineage. Clonality of the native and introduced lineages makes it possible to control for genetic variation, making P. australis a unique system for the comparative study of plasticity. Using previously identified clonal genotypes, we investigated differences in their phenotypic plasticity through measurements of the lengths and densities of stomata on both the abaxial (lower) and adaxial (upper) surfaces of leaves, and synthesized these measurements to estimate impacts on maximum stomatal conductance to water (gwmax). Results demonstrated that at three marsh sites, invasive lineages have consistently greater gwmax than their native congeners, as a result of greater stomatal densities and smaller stomata. Our analysis also suggests that phenotypic plasticity, determined as within-genotype variation in gwmax, of the invasive lineage is similar to, or exceeds, that shown by the native lineage. PMID- 26819258 TI - Changes in composition, ecology and structure of high-mountain vegetation: a re visitation study over 42 years. AB - High-mountain ecosystems are increasingly threatened by climate change, causing biodiversity loss, habitat degradation and landscape modifications. However, very few detailed studies have focussed on plant biodiversity in the high mountains of the Mediterranean. In this study, we investigated the long-term changes that have occurred in the composition, structure and ecology of high-mountain vegetation in the central Apennines (Majella) over the last 42 years. We performed a re visitation study, using historical and newly collected vegetation data to explore which ecological and structural features have been the most successful in coping with climatic changes. Vegetation changes were analysed by comparing geo referenced phytosociological releves collected in high-mountain habitats (dolines, gentle slopes and ridges) on the Majella massif in 1972 and in 2014. Composition analysis was performed by detrended correspondence analysis, followed by an analysis of similarities for statistical significance assessment and by similarity percentage procedure (SIMPER) for identifying which species indicate temporal changes. Changes in ecological and structural indicators were analysed by a permutational multivariate analysis of variance, followed by a post hoc comparison. Over the last 42 years, clear floristic changes and significant ecological and structural variations occurred. We observed a significant increase in the thermophilic and mesonitrophilic plant species and an increment in the frequencies of hemicryptophytes. This re-visitation study in the Apennines agrees with observations in other alpine ecosystems, providing new insights for a better understanding of the effects of global change on Mediterranean high-mountain biodiversity. The observed changes in floristic composition, the thermophilization process and the shift towards a more nutrient-demanding vegetation are likely attributable to the combined effect of higher temperatures and the increase in soil nutrients triggered by global change. The re-visitation approach adopted herein represents a powerful tool for studying climate-related changes in sensitive high-mountain habitats. PMID- 26819256 TI - Effect of Induced Pluripotent Stem Cell Technology in Blood Banking. AB - Population aging has imposed cost-effective alternatives to blood donations. Artificial blood is still at the preliminary stages of development, and the need for viable cells seems unsurmountable. Because large numbers of viable cells must be promptly available for clinical use, stem cell technologies, expansion, and banking represent ideal tools to ensure a regular supply. Provided key donors can be identified, induced pluripotent stem cell (iPSC) technology could pave the way to a new era in transfusion medicine, just as it is already doing in many other fields of medicine. The present review summarizes the current state of research on iPSC technology in the field of blood banking, highlighting hurdles, and promises. PMID- 26819259 TI - Biomechanics and functional morphology of a climbing monocot. AB - Plants with a climbing growth habit possess unique biomechanical properties arising from adaptations to changing loading conditions connected with close attachment to mechanical supports. In monocot climbers, mechanical adaptation is restricted by the absence of a bifacial vascular cambium. Flagellaria indica was used to investigate the mechanical properties and adaptations of a monocot climber that, uniquely, attaches to the surrounding vegetation via leaf tendrils. Biomechanical methods such as three-point bending and torsion tests were used together with anatomical studies on tissue development, modification and distribution. In general, the torsional modulus was lower than the bending modulus; hence, torsional stiffness was less than flexural stiffness. Basal parts of mature stems showed the greatest stiffness while that of more apical stem segments levelled off. Mechanical properties were modulated via tissue maturation processes mainly affecting the peripheral region of the stem. Peripheral vascular bundles showed a reduction in the amount of conducting tissue while the proportion and density of the bundle sheath increased. Furthermore, adjacent bundle sheaths merged resulting in a dense ring of fibrous tissue. Although F. indica lacks secondary cambial growth, the climbing habit is facilitated by a complex interaction of tissue maturation and attachment. PMID- 26819260 TI - Doctors' risks of formal patient complaints and the challenge of predicting complaint behaviour. PMID- 26819261 TI - Diagnosis and management of diabetes in children and young people: summary of updated NICE guidance. PMID- 26819262 TI - Genetic loci for Epstein-Barr virus nuclear antigen-1 are associated with risk of multiple sclerosis. AB - BACKGROUND: Infection with the Epstein-Barr virus (EBV) is associated with an increased risk of multiple sclerosis (MS). OBJECTIVE: We sought genetic loci influencing EBV nuclear antigen-1 (EBNA-1) IgG titers and hypothesized that they may play a role in MS risk. METHODS: We performed a genome-wide association study (GWAS) of anti-EBNA-1 IgG titers in 3599 individuals from an unselected twin family cohort, followed by a meta-analysis with data from an independent EBNA-1 GWAS. We then examined the shared polygenic risk between the EBNA-1 GWAS (effective sample size (Neff) = 5555) and a large MS GWAS (Neff = 15,231). RESULTS: We identified one locus of strong association within the human leukocyte antigen (HLA) region, of which the most significantly associated genotyped single nucleotide polymorphism (SNP) was rs2516049 (p = 4.11 * 10-9). A meta-analysis including data from another EBNA-1 GWAS in a cohort of Mexican-American families confirmed that rs2516049 remained the most significantly associated SNP (p = 3.32 * 10-20). By examining the shared polygenic risk, we show that the genetic risk for elevated anti-EBNA-1 titers is positively correlated with the development of MS, and that elevated EBNA-1 titers are not an epiphenomena secondary to MS. In the joint meta-analysis of EBNA-1 titers and MS, loci at 1p22.1, 3p24.1, 3q13.33, and 10p15.1 reached genome-wide significance (p < 5 * 10-8). CONCLUSIONS: Our results suggest that apart from the confirmed HLA region, the association of anti EBNA-1 IgG titer with MS risk is also mediated through non-HLA genes, and that studies aimed at identifying genetic loci influencing EBNA immune response provides a novel opportunity to identify new and characterize existing genetic risk factors for MS. PMID- 26819263 TI - High-resolution myelin water imaging in post-mortem multiple sclerosis spinal cord: A case report. AB - BACKGROUND: Loss of myelin in the spinal cord in multiple sclerosis (MS) is likely an important, and early, contributor to atrophy and associated disability. In vivo measurement of myelin is possible using myelin water fraction (MWF) imaging, but MWF has never been assessed in MS along the entire length of the spinal cord in vivo or in post-mortem tissue. OBJECTIVE: To assess the feasibility of measuring the distribution of MWF along the entire length of the spinal cord in post-mortem MS tissue using high-field MRI. METHODS: One formalin fixed spinal cord from a female with secondary progressive MS (age: 78 years, disease duration: 25 years) was cut into 104 5-mm-thick cross sections along the entire length of the spinal cord from the cervico-medullary junction to the conus medullaris and imaged using a 64 echo T2 relaxation experiment at 7T. RESULTS: Myelin water maps showed cord anatomy in superb detail, white matter demonstrating a higher MWF than the grey matter. Anatomical variation in myelin distribution along cervical, thoracic and lumbar regions was observed. Lesions demonstrated myelin loss. CONCLUSION: Post-mortem myelin water imaging of formalin-fixed MS spinal cord is feasible. PMID- 26819264 TI - Cancer Incidence in Appalachia, 2004-2011. AB - BACKGROUND: Limited literature is available about cancer in the Appalachian Region. This is the only known analysis of all cancers for Appalachia and non Appalachia covering 100% of the US population. Appalachian cancer incidence and trends were evaluated by state, sex, and race and compared with those found in non-Appalachian regions. METHODS: US counties were identified as Appalachian or non-Appalachian. Age-adjusted cancer incidence rates, standard errors, and confidence intervals were calculated using the most recent data from the United States Cancer Statistics for 2004 to 2011. RESULTS: Generally, Appalachia carries a higher cancer burden compared with non-Appalachia, particularly for tobacco related cancers. For all cancer sites combined, Appalachia has higher rates regardless of sex, race, or region. The Appalachia and non-Appalachia cancer incidence gap has narrowed, with the exception of oral cavity and pharynx, larynx, lung and bronchus, and thyroid cancers. CONCLUSIONS: Higher cancer incidence continues in Appalachia and appears at least in part to reflect high tobacco use and potential differences in socioeconomic status, other risk factors, patient health care utilization, or provider practices. It is important to continue to evaluate this population to monitor results from screening and early detection programs, understand behavioral risk factors related to cancer incidence, increase efforts to reduce tobacco use and increase cancer screening, and identify other areas where effective interventions may mediate disparities. IMPACT: Surveillance and evaluation of special populations provide means to monitor screening and early detection programs, understand behavioral risk factors, and increase efforts to reduce tobacco use to mediate disparities. PMID- 26819265 TI - Statin Use and Prostate Cancer Aggressiveness: Results from the Population-Based North Carolina-Louisiana Prostate Cancer Project. AB - BACKGROUND: Although statin use has been associated with reduced prostate cancer aggressiveness, the impact of race and patient characteristics on this association is not well understood. We examined the association between statin use and prostate cancer aggressiveness in Caucasians (CA) and African Americans (AA) and explored effect modification by health-seeking behaviors associated with statin use. METHODS: Of 1,930 cases from The North Carolina-Louisiana Prostate Cancer Project, 344 (18%) were classified as aggressive based on clinical criteria. Utilizing nonaggressive cases as referent, logistic regression was used to examine the association between statin use and prostate cancer aggressiveness, overall and stratified by race. Smoking and prostate cancer screening were examined as effect modifiers of this association. RESULTS: There was an inverse association between statin use and prostate cancer aggressiveness [OR, 0.74; 95% confidence interval (CI), 0.56-0.96], with comparable effect estimates in both races. Although not statistically significant, statin use was associated with reduced ORs for aggressive prostate cancer in never-screened men (OR, 0.79; 95% CI, 0.45-1.39), men screened at low/recommended frequency (<=once/year; OR, 0.66; 95% CI, 0.41-1.06), and men screened at high frequency (>once/year; OR, 0.78; 95% CI, 0.53-1.15). Inverse associations between statins and aggressive prostate cancer were strongest in never smokers (OR, 0.42; 95% CI, 0.25-0.72), attenuated in former smokers (OR, 0.84; 95% CI, 0.59-1.19), and absent in current smokers (OR, 1.36; 95% CI, 0.70-2.64). CONCLUSIONS: Statin use was associated with reduced prostate cancer aggressiveness in CA and AAs, with strongest inverse associations in nonsmokers. IMPACT: Health-seeking behaviors associated with statin use should be considered when examining the impact of statins on prostate cancer aggressiveness. Cancer Epidemiol Biomarkers Prev; 25(4); 670-7. (c)2016 AACR. PMID- 26819266 TI - What Predicts an Advanced-Stage Diagnosis of Breast Cancer? Sorting Out the Influence of Method of Detection, Access to Care, and Biologic Factors. AB - BACKGROUND: Multiple studies have yielded important findings regarding the determinants of an advanced-stage diagnosis of breast cancer. We seek to advance this line of inquiry through a broadened conceptual framework and accompanying statistical modeling strategy that recognize the dual importance of access-to care and biologic factors on stage. METHODS: The Centers for Disease Control and Prevention-sponsored Breast and Prostate Cancer Data Quality and Patterns of Care Study yielded a seven-state, cancer registry-derived population-based sample of 9,142 women diagnosed with a first primary in situ or invasive breast cancer in 2004. The likelihood of advanced-stage cancer (American Joint Committee on Cancer IIIB, IIIC, or IV) was investigated through multivariable regression modeling, with base-case analyses using the method of instrumental variables (IV) to detect and correct for possible selection bias. The robustness of base-case findings was examined through extensive sensitivity analyses. RESULTS: Advanced-stage disease was negatively associated with detection by mammography (P < 0.001) and with age < 50 (P < 0.001), and positively related to black race (P = 0.07), not being privately insured [Medicaid (P = 0.01), Medicare (P = 0.04), uninsured (P = 0.07)], being single (P = 0.06), body mass index > 40 (P = 0.001), a HER2 type tumor (P < 0.001), and tumor grade not well differentiated (P < 0.001). This IV model detected and adjusted for significant selection effects associated with method of detection (P = 0.02). Sensitivity analyses generally supported these base-case results. CONCLUSIONS: Through our comprehensive modeling strategy and sensitivity analyses, we provide new estimates of the magnitude and robustness of the determinants of advanced-stage breast cancer. IMPACT: Statistical approaches frequently used to address observational data biases in treatment-outcome studies can be applied similarly in analyses of the determinants of stage at diagnosis. Cancer Epidemiol Biomarkers Prev; 25(4); 613-23. (c)2016 AACR. PMID- 26819267 TI - Adverse drug reactions in neonates: a prospective study. AB - AIM: To investigate the frequency and characteristics of adverse drug reactions (ADRs) in hospitalised neonates to obtain a better understanding of and improvement in neonatal healthcare. METHODOLOGY: A prospective cohort study. Data were collected on 313 neonates and 2166 drug prescriptions. Clinical characteristics of patients, drugs administered and ADRs were prospectively recorded and analysed. Informed consent was obtained in all cases. RESULTS: 116 different ADRs were detected. 17% of the neonates experienced at least one of these ADRs. Systemic antimicrobials and caffeine citrate were the drugs that most commonly caused ADRs. According to the ADR Severity Assessment Scale, 41% were mild, 42% were moderate and 17% were severe. Of the ADRs identified, 11% were classified as 'certain' by the Naranjo method and 20% were classified as 'defined' by the Karch and Lasagna modified algorithm. Most of the ADRs detected were related to feed intolerance, phlebitis and tachycardia. Most were acute (73%) and lasted between 1 and 7 days (39%). After the occurrence of an ADR, it was necessary to initiate specific treatment in 44 cases, discontinue the drugs involved in 30 cases, and reduce the drug dose in another 30 cases. An association was shown between the number of drugs prescribed and ADR onset. CONCLUSIONS: There is a high incidence of ADRs in hospitalised newborns, which increases with the number of prescriptions. PMID- 26819268 TI - Antenatal diagnosis of critical congenital heart disease. Optimal place of delivery is where appropriate care can be delivered. PMID- 26819270 TI - Prolyl-hydroxylase inhibitor activating hypoxia-inducible transcription factors reduce levels of transplant arteriosclerosis in a murine aortic allograft model. AB - OBJECTIVES: The development of transplant arteriosclerosis, the hallmark feature of heart transplant rejection, is associated with a chronic immune response and also influenced by an initial injury to the graft through ischaemia and reperfusion. Hypoxia-inducible transcription factor (HIF)-1 pathway signalling has a protective effect against ischaemia-reperfusion injury and has already been demonstrated to ameliorate allograft nephropathy in previous animal studies. Therefore, the aim of this study was to investigate the effect of stabilization of hypoxia-inducible transcription factors with a prolyl-hydroxylase domain (PHD) inhibitor on transplant arteriosclerosis in an experimental aortic allograft model. METHODS: MHC-class I mismatched C.B10-H2(b)/LilMcdJ donor thoracic aortas were heterotopically transplanted into the abdominal aorta of BALB/c mice. Donor animals received a single dose of the PHD inhibitor 2-(1-chloro-4 hydroxyisoquinoline-3-carboxamido) acetate (ICA) (40 mg/kg) or vehicle i.p. 4 h before transplantation. Intragraft HIF accumulation after ICA treatment was detected by immunohistochemistry before and after cold ischaemia (n = 5). Grafts were harvested 30 days after transplantation and analysed by histology (n = 7) and immunofluorescence (n = 7). In addition, intragraft mRNA expression for cytokines, adhesion molecules and growth factors was determined on Day 14 (n = 7). RESULTS: Donor preconditioning with ICA resulted in HIF accumulation in the aorta and induction of the HIF target genes vascular endothelial growth factor and transforming growth factor-beta. Vascular lesions were present in both experimental groups. However, there was significantly reduced intimal proliferation in preconditioned grafts when compared with vehicle controls [intimal proliferation 31.3 +/- 8% (ICA) vs 55.3 +/- 20% (control), P < 0.01]. In addition, experimental groups revealed a down-regulation of E-selectin (-57%) and MCP1 (-33%) expression after ICA pretreatment compared with controls, going along with decreased T-cell [1.4% CD4+ T-cell infiltration vs 8.4% (control) and 4.9% CD8+ T-cell infiltration vs 10.7% (control)], dendritic cell (0.6% dendritic cells infiltration vs 1.9% infiltration(control)] and macrophage infiltration [4.8% macrophages (ICA) vs 10.9% (control)] within vascular grafts. CONCLUSIONS: These data of an animal transplant model show that the pharmaceutical activation of HIF with endogenous up-regulation of protective target genes leads to adaptation of the graft to low oxygen-saturation and hereby attenuates the development of transplant arteriosclerosis and allograft injury. Pharmaceutical inhibition of PHDs appears to be a very attractive strategy for organ preservation that deserves further clinical evaluation. PMID- 26819271 TI - Bridging to lung transplantation for severe pulmonary hypertension using dual central Novalung lung assist devices. AB - This case describes the technique of using dual Novalungs (a pumpless extracorporeal system) to bridge a patient with idiopathic pulmonary hypertension to bilateral lung transplantation. A 41-year old lady with idiopathic pulmonary hypertension (with a possible veno-occlusive element) presented with symptoms of end-stage heart and lung failure. This was refractory to medical management with iloprost, sildenafil and bosentan. The patient was placed on the urgent waiting list for lung transplantation and central pulmonary artery to left atrial Novalung insertion was performed. Local anaesthetic was given before performing peripheral cardiopulmonary bypass due to the high risk of cardiac arrest. Two days later, donor organs became available and the patient was taken for double lung transplantation. The pulmonary artery cannula was removed leaving a large defect. This was then closed using a bovine pericardial patch. Due to the damaged right superior pulmonary vein from Novalung cannulation, cardioplegia was given to facilitate an open atrial anastomosis. After 13 days in the intensive therapy unit, she was transferred to the ward. There were no further complications and she has been discharged home. PMID- 26819269 TI - Use of minimal invasive extracorporeal circulation in cardiac surgery: principles, definitions and potential benefits. A position paper from the Minimal invasive Extra-Corporeal Technologies international Society (MiECTiS). AB - Minimal invasive extracorporeal circulation (MiECC) systems have initiated important efforts within science and technology to further improve the biocompatibility of cardiopulmonary bypass components to minimize the adverse effects and improve end-organ protection. The Minimal invasive Extra-Corporeal Technologies international Society was founded to create an international forum for the exchange of ideas on clinical application and research of minimal invasive extracorporeal circulation technology. The present work is a consensus document developed to standardize the terminology and the definition of minimal invasive extracorporeal circulation technology as well as to provide recommendations for the clinical practice. The goal of this manuscript is to promote the use of MiECC systems into clinical practice as a multidisciplinary strategy involving cardiac surgeons, anaesthesiologists and perfusionists. PMID- 26819272 TI - Simultaneous stapling of the lobar bronchus and pulmonary artery: is it actually dangerous? AB - We performed a left caudal lobectomy on a 3-month old male swine. During the lobectomy, the lobar bronchus and pulmonary artery were stapled simultaneously using an endostapler. According to a postmortem examination 42 days after the operation, the stumps were surrounded by granulation tissue with prominent accumulation of inflammatory cells. With respect to the bronchus, the stapled tissue remained as it was just after stapling, without degradation of the cartilage, smooth muscle or epithelial layers. In contrast, with respect to the pulmonary artery, the stapled tissue disappeared, which resulted in the formation of a new vascular stump with recruitment of a new adventitial layer and fibrotic tissue. Therefore, despite the simultaneous stapling, the vascular stump was separated from the bronchial stump. Our results suggest that the process of stump healing after stapling of the bronchus is different from that after stapling of the pulmonary artery: bronchial stump healing consists of extraluminal covering of the fibrotic tissues, while pulmonary arterial stump healing consists of intraluminal reformation of the intima and media. On the basis of the results, we believe that a bronchovascular fistula will not develop after simultaneous bronchovascular stapling unless the anterior wall of the bronchus has fallen away due to major stump necrosis. PMID- 26819273 TI - The preventive role of the posterior pericardial window in the development of late cardiac tamponade following heart valve surgery. AB - OBJECTIVES: It is reported that creating a window from the posterior pericardium into the left pleural cavity during coronary bypass surgeries reduces postoperative late cardiac tamponades. Although late tamponades are more common after heart valve surgeries, this procedure is not generally performed. The present study investigated whether creating a window has a preventive effect on the formation of late cardiac tamponade after heart valve surgeries. METHODS: The study was conducted on all patients (n = 262) in whom one or more valves were replaced and who fulfilled the study criteria between January 2010 and October 2014 in one centre. We began to create a posterior pericardial window in all valvular patients from March 2012. One hundred and thirty-five patients operated on before this date (Non-Window Group) and 127 patients after this date (Window Group) were compared for the development of late cardiac tamponade. RESULTS: There were no differences between the groups in terms of preoperative and intraoperative characteristics. Late pericardial tamponade was not observed in any patients from the Window Group, whereas it occurred in 7 (5.2%) patients from the Non-Window Group (P = 0.015). Three patients died in total; all 3 were from the Non-Window Group. One of the mortalities was associated with tamponade. CONCLUSIONS: Creating a pericardial window may reduce late cardiac tamponade events/episodes, which may be a fatal complication in valve patients. We recommend performing this procedure by allocating some time during the surgical procedure in order to avoid tamponade. PMID- 26819274 TI - Unexpected results after sternal reconstruction with plates, cables and cannulated screws. AB - OBJECTIVES: During the last decade, various plate fixation systems have been developed for the treatment of complicated sternal dehiscence after open-heart surgery. One of them is the Modular Sternal Cable System(c) (MSCS), which promises optimal distribution of forces along the whole sternum by using plates, cannulated screws and cables. However, in comparison with other systems, there is a lack of outcome data. METHODS: Sternal reconstruction with the MSCS was performed in 11 patients (male n = 10, age 72.0 +/- 7.3 years) with complicated sternal dehiscence following cardiac surgery, and 73% of them had a history of sternal infection. Sternal reconstruction included bilateral longitudinal plating and thoracic re-closure with 4-9 cables. Patients received postoperative examination, focusing on sternal wound conditions and clinical stability. If there was any suspicion of recurrent wound infection, computed tomographic scans were done in the early postoperative period or in the long term, in order to evaluate bony consolidation and integrity of osteosynthetic material. RESULTS: The mean operation time was 165 +/- 59 min, the mean intubation time 4.7 +/- 5.3 min and the mean intensive care unit length of stay was 1 day (median) (range 1 23 days), with a total hospital stay of 9 days (median) (range 5-64 days). Operative mortality was 0%. One patient died on the 65th postoperative day of a non-MSCS-related cause. Sternal wound infection occurred in 6 patients (54.5%) and made hardware removal necessary in 5 of them early postoperatively (median 14 days) and in 1 patient late postoperatively (1058 days). In another patient, material was removed 715 days after MSCS application due to persisting sternal pain. CONCLUSIONS: A high incidence of postoperative wound infections was observed after implantation of the MSCS. It may be speculated that hardware design (e.g. the absence of a locking system, large screws) compromises osseous microcirculation, favouring the development of infection. This should be kept in mind for further development of sternal reconstruction systems. PMID- 26819276 TI - NKCC1-Mediated GABAergic Signaling Promotes Postnatal Cell Death in Neocortical Cajal-Retzius Cells. AB - During early development, a substantial proportion of central neurons undergoes programmed cell death. This activity-dependent process is essential for the proper structural and functional development of the brain. To uncover cell type specific differences in the regulation of neuronal survival versus apoptosis, we studied activity-regulated cell death in Cajal-Retzius neurons (CRNs) and the overall neuronal population in the developing mouse cerebral cortex. CRNs in the upper neocortical layer represent an early-born neuronal population, which is important for cortical development and largely disappears by apoptosis during neonatal stages. In contrast to the overall neuronal population, activity blockade with tetrodotoxin improved survival of CRNs in culture. Activation of GABAA receptors also blocked spontaneous activity and caused overall cell death including apoptosis of CRNs. Blockade of the Na-K-Cl transporter NKCC1 in vitro or its genetic deletion in vivo rescued CRNs from apoptosis. This effect was mediated by blockade of the p75NTR receptor signaling pathway. In summary, we discovered a novel developmental death pathway mediated by NKCC1, via GABAA receptor-mediated membrane depolarization and p75NTR signaling in CRNs. This pathway controls apoptosis of CRNs and may be critically involved in neurodevelopmental disorders such as autism and schizophrenia. PMID- 26819275 TI - Unaltered Network Activity and Interneuronal Firing During Spontaneous Cortical Dynamics In Vivo in a Mouse Model of Severe Myoclonic Epilepsy of Infancy. AB - Severe myoclonic epilepsy of infancy (SMEI) is associated with loss of function of the SCN1A gene encoding the NaV1.1 sodium channel isoform. Previous studies in Scn1a(-/+) mice during the pre-epileptic period reported selective reduction in interneuron excitability and proposed this as the main pathological mechanism underlying SMEI. Yet, the functional consequences of this interneuronal dysfunction at the circuit level in vivo are unknown. Here, we investigated whether Scn1a(-/+) mice showed alterations in cortical network function. We found that various forms of spontaneous network activity were similar in Scn1a(-/+) during the pre-epileptic period compared with wild-type (WT) in vivo. Importantly, in brain slices from Scn1a(-/+) mice, the excitability of parvalbumin (PV) and somatostatin (SST) interneurons was reduced, epileptiform activity propagated more rapidly, and complex synaptic changes were observed. However, in vivo, optogenetic reduction of firing in PV or SST cells in WT mice modified ongoing network activities, and juxtasomal recordings from identified PV and SST interneurons showed unaffected interneuronal firing during spontaneous cortical dynamics in Scn1a(-/+) compared with WT. These results demonstrate that interneuronal hypoexcitability is not observed in Scn1a(-/+) mice during spontaneous activities in vivo and suggest that additional mechanisms may contribute to homeostatic rearrangements and the pathogenesis of SMEI. PMID- 26819277 TI - Current status of immunotherapy. AB - The successful use of immune checkpoint inhibitors has been big breakthrough in the development of cancer immunotherapy. Anti-CTLA-4 monoclonal antibody, ipilimumab, is the first-approved immune checkpoint inhibitor and has shown durable objective responses for advanced melanoma beyond the effect of dacarbazine. Anti-PD-1 monoclonal antibodies, nivolumab and pembrolizumab, are other immune checkpoint inhibitors that have demonstrated more effective results than conventional drugs in clinical trials for a variety of advanced solid tumors including melanoma, non-small cell lung carcinoma and renal carcinoma. These studies have indicated that the enhancement of anti-cancer immunity by controlling the immune suppressive environment in cancer tissues is an important issue for the development of cancer immune-therapy. Accordingly, in recent years, the enthusiasm for research of cancer immunology has shifted to studies regarding the formation of the immune suppressive environment, immune suppression mechanisms in cancer tissues and the molecules and cells involved in these pathways. Novel findings from these studies might lead to the development of cancer immunotherapy based on control of the immune suppressive environment. PMID- 26819278 TI - Prognostic nomogram for previously untreated patients with esophageal squamous cell carcinoma after esophagectomy followed by adjuvant chemotherapy. AB - OBJECTIVE: The aim of the study was to establish an effective prognostic nomogram for esophageal squamous cell carcinoma after radical esophagectomy followed by adjuvant chemotherapy in those previously untreated patients. METHODS: The clinicopathological data from 328 patients who underwent radical esophagectomy followed by adjuvant chemotherapy or not at the Tianjin Medical University Cancer Institute and Hospital between 2006 and 2010 were retrospectively studied. Nomograms which predicted survival of esophageal squamous cell carcinoma were established based on the Cox proportional hazards regression model. To determine its predictive accuracy and discriminatory capacity, the concordance index and calibration curve were calculated after bootstrapping in the internal validation. An external validation of 76 patients in 2011 was prospectively studied at the same institution. To verify the performance of the nomogram, the comparison between the nomogram and Tumor-Node-Metastasis staging system was conducted. RESULTS: The 5-year overall survival was 43.1% in the primary cohort. Based on multivariate analyses, five independent prognostic variables including gender, tumor length, T stage, N stage and chemotherapy cycles were selected to build the nomograms to predict disease-free survival and overall survival. The concordance index of the nomogram to predict overall survival was 0.71 (95% confidence interval, 0.63-0.79), which was superior to the predictive power of Tumor-Node Metastasis staging system (0.64) in the primary cohort. Meanwhile, the calibration curve showed good accuracy between predictive and actual overall survival. In the validation cohort, the concordance index (0.77) and calibration plot displayed favorable performances. The other nomogram to predict disease-free survival also performed well. CONCLUSIONS: The prognostic nomogram provided individualized risk estimate of survival in patients after esophagectomy followed by adjuvant chemotherapy. PMID- 26819279 TI - Laparoscopic gastrointestinal anastomoses using knotless barbed absorbable sutures are safe and reproducible: a single-center experience with 242 patients. AB - OBJECTIVE: Intracorporeal reconstruction of the digestive tract is technically challenging. The V-Loc 180 wound closure device (Covidien) is a self-anchoring unidirectional barbed suture that obviates the need for knot tying. The aim of this prospective cohort study was to investigate the use of the novel suture in gastrointestinal enterotomy closure. METHODS: The subjects comprised patients with malignant disease who were scheduled to undergo laparoscopic gastrectomy with curative intent. The barbed suture was used to close the entry hole for the linear stapler during intracorporeal reconstruction following laparoscopic gastric resection. The primary endpoint was the proportion of patients who developed anastomotic leakage at the site where the barbed suture was applied. RESULTS: Between July 2012 and March 2015, 242 patients were enrolled. Of 362 anastomoses, the enterotomy hole at 256 sites was closed using the barbed suture. These 256 sites consisted of 95 gastroduodenostomies, 25 gastrogastrostomies, 13 gastrojejunostomies, 90 jejunojejunostomies, 17 esophagojejunostomies and 16 primary closures of the stomach following local gastric resection. There were no anastomosis-related complications, conversion to usual sutures, mechanical closure of the entry hole and reoperation due to adhesive obstructions or mortality over a median follow-up period of 17.8 months. CONCLUSIONS: The use of the unidirectional barbed absorbable suture for gastrointestinal closure is safe and effective in laparoscopic gastrectomy. PMID- 26819280 TI - ATAD2 overexpression is associated with progression and prognosis in colorectal cancer. AB - OBJECTIVES: ATPase family AAA domain-containing 2 plays an important role in tumor progression including cell cycle, proliferation, apoptosis and chemoresistance. However, the expression of ATPase family AAA domain-containing 2 in colorectal cancer and its significance are still unclear. The aim of this study was to examine the expression of ATPase family AAA domain-containing 2 in colorectal cancer. METHODS: Immunohistochemistry was used to determine the expression of ATPase family AAA domain-containing 2 in 155 colorectal cancer and 30 matched adjacent noncancerous tissues. The correlation of ATPase family AAA domain-containing 2 expression with clinicopathological variables was assessed using chi-square test. Patient survival was analyzed using the Kaplan-Meier and log-rank tests. Cox regression was performed for the multivariate analysis of prognostic factors. RESULTS: High expression of ATPase family AAA domain containing 2 was detected in 58.1% of the colorectal cancers and was significantly associated with advanced tumor-node-metastasis stage (P = 0.044), poor differentiation (P = 0.028), deep infiltration (P < 0.001), lymphovascular invasion (P = 0.006), lymph node metastasis (P = 0.024) and recurrence (P = 0.022). Patients with high ATPase family AAA domain-containing 2 expression had significantly poorer overall survival and disease-free survival (both P < 0.001) when compared with patients with low expression of ATPase family AAA domain containing 2. The multivariate analysis showed that ATPase family AAA domain containing 2 was an independent factor for both overall survival (P = 0.003; hazard ratio (HR): 2.356; 95% confidence interval (CI): 1.335-4.158) and disease free survival (P = 0.001; HR: 2.643; 95% CI: 1.489-4.693). CONCLUSIONS: These results showed that ATPase family AAA domain-containing 2 overexpression was associated with progression and prognosis of colorectal cancer. PMID- 26819281 TI - Upper gastrointestinal tumours in Japanese familial adenomatous polyposis patients. AB - OBJECTIVE: The upper gastrointestinal characteristics in Japanese familial adenomatous polyposis patients have not yet been clarified. The aim of the present study was to elucidate these characteristics in Japanese familial adenomatous polyposis patients. METHODS: This study was conducted by the study group for familial adenomatous polyposis in the Japanese Society for Cancer of the Colon and Rectum. Familial adenomatous polyposis patients who underwent surgical resection from 2000 to 2012 were included in the study. RESULTS: In total, 303 familial adenomatous polyposis patients were enrolled, with 265 cases of classical familial adenomatous polyposis (>=100 adenomas) and 38 cases of attenuated familial adenomatous polyposis (<100 adenomas). Fundic gland polyps were significantly more common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis; however, gastric cancer was significantly less common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis. Gastric cancer and duodenal adenoma were significantly more common in familial adenomatous polyposis patients with gastric adenoma than in those without gastric adenoma. Duodenal cancer was detected in 7 of 72 familial adenomatous polyposis patients with duodenal adenoma. The median tumour risk in 50-year-old familial adenomatous polyposis patients was 55.3, 21.8, 3.8, 39.2 and 7.7% for fundic gland polyp, gastric adenoma, gastric cancer, duodenal adenoma and duodenal cancer, respectively. CONCLUSIONS: Upper gastrointestinal tumours/polyps were frequently found in familial adenomatous polyposis patients, and their incidences were correlated; however, the frequency of gastric cancer in Japanese familial adenomatous polyposis patients was similar to that in the general population. PMID- 26819282 TI - Frontal D2/3 Receptor Availability in Schizophrenia Patients Before and After Their First Antipsychotic Treatment: Relation to Cognitive Functions and Psychopathology. AB - BACKGROUND: We have previously reported associations between frontal D2/3 receptor binding potential positive symptoms and cognitive deficits in antipsychotic-naive schizophrenia patients. Here, we examined the effect of dopamine D2/3 receptor blockade on cognition. Additionally, we explored the relation between frontal D2/3 receptor availability and treatment effect on positive symptoms. METHODS: Twenty-five antipsychotic-naive first-episode schizophrenia patients were examined with the Positive and Negative Syndrome Scale, tested with the cognitive test battery Cambridge Neuropsychological Test Automated Battery, scanned with single-photon emission computerized tomography using the dopamine D2/3 receptor ligand [(123)I]epidepride, and scanned with MRI. After 3 months of treatment with either risperidone (n=13) or zuclopenthixol (n=9), 22 patients were reexamined. RESULTS: Blockade of extrastriatal dopamine D2/3 receptors was correlated with decreased attentional focus (r = -0.615, P=.003) and planning time (r = -0.436, P=.048). Moreover, baseline frontal dopamine D2/3 binding potential and positive symptom reduction correlated positively (D2/3 receptor binding potential left frontal cortex rho = 0.56, P=.003; D2/3 receptor binding potential right frontal cortex rho = 0.48, P=.016). CONCLUSIONS: Our data support the hypothesis of a negative influence of D2/3 receptor blockade on specific cognitive functions in schizophrenia. This is highly clinically relevant given the well-established association between severity of cognitive disturbances and a poor functional outcome in schizophrenia. Additionally, the findings support associations between frontal D2/3 receptor binding potential at baseline and the effect of antipsychotic treatment on positive symptoms. PMID- 26819284 TI - Re: Blood flow analysis of the aortic arch using computational fluid dynamics. PMID- 26819283 TI - Maternal Immune Activation Disrupts Dopamine System in the Offspring. AB - BACKGROUND: In utero exposure to maternal viral infections is associated with a higher incidence of psychiatric disorders with a supposed neurodevelopmental origin, including schizophrenia. Hence, immune response factors exert a negative impact on brain maturation that predisposes the offspring to the emergence of pathological phenotypes later in life. Although ventral tegmental area dopamine neurons and their target regions play essential roles in the pathophysiology of psychoses, it remains to be fully elucidated how dopamine activity and functionality are disrupted in maternal immune activation models of schizophrenia. METHODS: Here, we used an immune-mediated neurodevelopmental disruption model based on prenatal administration of the polyriboinosinic polyribocytidilic acid in rats, which mimics a viral infection and recapitulates behavioral abnormalities relevant to psychiatric disorders in the offspring. Extracellular dopamine levels were measured by brain microdialysis in both the nucleus accumbens shell and the medial prefrontal cortex, whereas dopamine neurons in ventral tegmental area were studied by in vivo electrophysiology. RESULTS: Polyriboinosinic-polyribocytidilic acid-treated animals, at adulthood, displayed deficits in sensorimotor gating, memory, and social interaction and increased baseline extracellular dopamine levels in the nucleus accumbens, but not in the prefrontal cortex. In polyriboinosinic-polyribocytidilic acid rats, dopamine neurons showed reduced spontaneously firing rate and population activity. CONCLUSIONS: These results confirm that maternal immune activation severely impairs dopamine system and that the polyriboinosinic-polyribocytidilic acid model can be considered a proper animal model of a psychiatric condition that fulfills a multidimensional set of validity criteria predictive of a human pathology. PMID- 26819285 TI - Long-term follow-up of patients undergoing aortic root enlargement for insertion of a larger prosthesis. AB - OBJECTIVES: To evaluate the long-term survival of patients undergoing aortic root enlargement (ARE) compared with those with small aortic root (SAR), exploring risk factors for late mortality as well as the influence of patient-prosthesis mismatch (PPM). METHODS: From January 1999 through December 2010, a total of 3724 patients underwent isolated or combined aortic valve replacement at our institution. From these, 239 (6.4%) had transannular ARE with a pericardial patch, to permit implantation of a larger prosthesis. This study population was compared with a control group of 767 patients (20.6%) who were considered to have SAR, as a prosthesis of size 21 or less was implanted. Mean age was comparable: 70.4 +/- 12.5 vs 69.9 +/- 9.6 years for ARE and SAR groups, respectively (P = 0.552). Female sex predominated in the control group (81.6 vs 88.0%; P = 0.011). Patients of the ARE group tended to have higher mean body surface area (1.59 +/- 0.15 vs 1.57 +/- 0.13 m(2); P = 0.061) and were less symptomatic (NYHA III-IV: 49.4 vs 57.9%; P = 0.021). RESULTS: Implantation of bioprostheses was more frequent in the ARE group (76.2 vs 52.3%; P < 0.001), while concomitant procedures were more frequent in the SAR group (25.5 vs 32.2%; P = 0.050). Patients in the SAR group had higher moderate PPM (29.7 vs 50.1%; P < 0.001), but no patient was left with severe PPM. Hospital mortality was not statistically different between ARE and SAR groups (0.8 vs 0.5%; P = 0.632). The overall survival rate for ARE group patients at 5, 10 and 15 years was 82.7 +/- 2.5, 64.8 +/- 3.8 and 36.0 +/- 7.5%, respectively, in comparison with 86.2 +/- 1.3, 62.9 +/ 2.3 and 38.4 +/- 4.3% for the SAR group (P = 0.741). There was no significant difference in long-term survival of ARE patients compared with the age- and gender-matched general population (P = 0.794). Long-term survival was not affected by the presence of PPM. Increasing age, male sex, atrial fibrillation, LV end-systolic dimension, preoperative creatinine and NYHA class III-IV were significant predictors of late mortality. CONCLUSIONS: ARE can be done safely, effectively reducing PPM. Although no difference was found in early and late mortality compared with the SAR group, long-term survival rates of ARE patients was comparable with that of the general population, unlike those of the SAR group. PMID- 26819286 TI - Central tumour location should be considered when comparing N1 upstaging between thoracoscopic and open surgery for clinical stage I non-small-cell lung cancer. AB - OBJECTIVES: Nodal upstaging is a quality indicator for oncological thoracic surgery and is found in up to 25% of patients with clinical stage I (cStage-I) non-small-cell lung cancer (NSCLC). In large retrospective series, lower N1 upstaging was reported after video-assisted thoracic surgery (VATS) resections. We studied the impact of central primary tumour location on nodal upstaging in cStage-I NSCLC. METHODS: Consecutive patients operated for cStage-I NSCLC were selected from a prospectively managed surgical database. Tumour location was classified as central if the lesion was visible during standard video bronchoscopy. A nodal station mapping was drawn for each patient based on final pathological examination. Univariable and additive multivariable binary logistic regression analyses were performed. RESULTS: Between 2007-2014, 334 patients underwent anatomical resection for cStage-I NSCLC, either by open thoracotomy (n = 158) or by VATS (n = 176; conversion rate 1.7%). All patients underwent imaging with [(18)F]-fluorodeoxyglucose positron emission tomography and computer tomography. Invasive mediastinal staging was performed in 24.6% of patients. There were more central tumours in the open group (24.1%, n = 38) compared with the VATS group (4.5%, n = 8). There was no significant difference between the number (mean +/- standard deviation) of nodal stations examined (open 5 +/- 1.9 vs VATS 5 +/- 1.7, P = 0.99). Pathological nodal upstaging was found in 15.9% (n = 53) of cStage-I patients. Nodal pN1 and pN2 upstaging were 13.3 and 8.2%, respectively, for the open group, and 6.3 and 4.5%, respectively, for the VATS group. In 32.6% (n = 15/46) of patients with a central cStage-I tumour pN1, upstaging was found. A binary logistic regression model (including tumour location, technique, tumour size, gender and histology) showed that only tumour location had a significant impact on pN1 upstaging [peripheral versus central; odds ratio (OR) 5.07 (confidence interval, CI: 1.89-13.60), P = 0.001], while surgical technique had no significant impact [VATS versus open; OR 0.74 (CI: 0.31 1.78), P = 0.50]. CONCLUSIONS: The number of lymph node stations examined during VATS resections is similar to open resections for cStage-I NSCLC. Almost one third of the patients with a central cStage-I NSCLC were upstaged to pN1. Tumour location was the only independent variable for pN1 upstaging in logistic regression analysis. It is a potential bias in retrospective studies and should therefore be accounted for when comparing different surgical resection techniques for cStage-I NSCLC. PMID- 26819287 TI - The Provisional Extension To Induce Complete Attachment (PETTICOAT) technique to promote distal aortic remodelling in repair of acute DeBakey type I aortic dissection: is the best the enemy of the good? PMID- 26819288 TI - Surgical experience in the rehabilitation and reimplantation of disconnected pulmonary arteries and its effectiveness in restoring pulmonary haemodynamics and function. AB - OBJECTIVES: We established a policy to restore disconnected pulmonary arteries (PAs), regardless of aetiology or cardiac pathology, using a protocol-based strategy. There are conflicting reports of the need to restore disconnected PA especially if severely hypoplastic with some groups advocating surgical repair of cardiac defects to single lung with moderate to high risk. METHODS: All patients referred to our PA reconstruction programme (2007-14) with complete separation of one branch PA were included. Our surgical strategy was based on the size of the PA. In patients with mild or no PA hypoplasia, we performed single-stage implantation of the disconnected PA and repair of intracardiac defects. Two-stage approach was used in patients with severe PA hypoplasia where the disconnected PA was retrieved inside the lung then connected to the aorta with a shunt to promote growth. After 6-12 months, the PA was implanted with simultaneous repair of intracardiac defects. RESULTS: Twenty patients were included (age range = 1 week to 8 years). Aetiologies were ductal origin of distal PA in 13 patients and iatrogenic in 7 patients. Group 1 (isolated lesion) consisted of 8 patients who presented with severe pulmonary hypertension. Group 2 consisted of 12 patients with associated intracardiac defects and was subdivided into Group 2a (biventricular hearts) 8 patients and Group 2b (univentricular hearts) 4 patients. Single-stage repair was achieved in 10 patients. Direct tissue-to tissue connection was achieved in 18 (90%) patients. The follow-up was 100% complete (median = 53.8 months). All patients are alive and asymptomatic. Implanted PAs are patent with good growth demonstrated on serial echocardiography. Only two PAs required balloon dilatation for moderate restenosis at the anastomosis. No surgical reintervention was needed. All Group 1 patients had complete resolution of the pulmonary hypertension. Lung perfusion scans showed increased uptake (24-53% of the total uptake). CONCLUSIONS: Our study demonstrated that, in paediatric age group, disconnected PAs can be restored with low risk and excellent outcomes even in patients with severely hypoplastic PA. Strategies to repair intracardiac defects to a single lung might not be the optimal approach. PMID- 26819289 TI - Lipoblastoma: an unusual tumour of the left ventricle. AB - Lipoblastoma is a rare benign tumour of infancy originating from white foetal adipose tissue. Most commonly located in the extremities, intrathoracic and mediastinal involvement of this tumour is rare, and an intracardiac location is even rarer, with only one reported case. Herein, we present a 2-month old asymptomatic boy diagnosed with an echogenic mass in the left ventricular outflow tract. The patient underwent surgical excision and histopathological evaluation revealed a lipoblastoma. PMID- 26819290 TI - Factors predicting occult lymph node metastasis in completely resected lung adenocarcinoma of 3 cm or smaller. AB - OBJECTIVES: The aim of the study is to demonstrate the relationship between clinicopathological variables and occult lymph node metastasis in resected lung adenocarcinoma. METHODS: The clinicopathological characteristics of 471 patients with clinical N2-negative status undergoing resection for lung adenocarcinoma of 3 cm or smaller at Taipei Veterans General Hospital between 2004 and 2012 were retrospectively reviewed. The association between clinicopathological variables and lymph node metastasis was analysed by univariate and multivariate logistic regression. RESULTS: Among the 471 patients, there were 386 (82.0%) patients with pathological N0 status, 35 (7.4%) with pathological N1 status and 50 (10.6%) with pathological N2 status. Greater tumour size (P = 0.002), presence of a micropapillary pattern (P < 0.001), presence of a solid pattern (P < 0.001) and predominant pattern group (micropapillary/solid predominant) (P = 0.001) were significantly associated with higher percentage of occult N2 lymph node metastasis. In multivariate analysis, greater tumour size (P = 0.008), presence of micropapillary pattern (P < 0.001) and presence of solid pattern (P = 0.001) were significant predictors of occult N2 lymph node metastasis in tumours of 3 cm or smaller. When histological pattern was entered as the predominant pattern in multivariate analysis, micropapillary/solid predominant pattern (P = 0.005) was also a significant predictor of occult N2 lymph node metastasis. CONCLUSIONS: The presence of micropapillary or solid pattern, as well as micropapillary/solid predominant pattern, is significantly associated with occult N2 lymph node metastasis in lung adenocarcinoma. Radical mediastinal lymph node dissection may help to identify occult lymph node metastasis in these patients. PMID- 26819291 TI - Successful heart transplant after 1374 days living with a total artificial heart. AB - The CardioWest Total Artificial Heart (CW-TAH) has been approved as a temporary device for bridge to cardiac transplantation and is under investigation for destination therapy by US Food and Drug Administration (FDA). We herein report the longest worldwide survival out of hospital (1374 days) of a patient supported with Cardio West Total Artificial Heart (CW-TAH). This experience is intended as a proof of concept of using CW-TAH as the destination therapy in patients with biventricular failure. PMID- 26819292 TI - Randomized comparison of exercise haemodynamics of Freestyle, Magna Ease and Trifecta bioprostheses after aortic valve replacement for severe aortic stenosis. AB - OBJECTIVES: The purpose of this study was to compare haemodynamics at rest and during exercise after clinically indicated aortic valve replacement (AVR) for aortic stenosis among patients randomly assigned to one of three haemodynamically excellent bioprostheses. METHODS: In a single-centre, prospective trial, 60 patients undergoing clinically indicated AVR were randomly assigned to Freestyle, Magna Ease or Trifecta bioprostheses. Six months after surgery, patients underwent supine bicycle stress echocardiography for the assessment of aortic valve haemodynamics. RESULTS: There were 5 protocol deviations from random valve assignments, and 4 patients did not return for follow-up stress echo, yielding a study group of 56 patients {17 Freestyle, 21 Magna Ease, 18 Trifecta; median age 70 [interquartile range (IQR) 63-78 years], 37 (66%) men}. There were no statistically significant differences between groups in valve size, concomitant procedures or exercise variables. Resting haemodynamics revealed significant differences between groups in mean gradient [Freestyle 7 (IQR 5-9) mmHg, Magna Ease 9 (IQR 7-11) mmHg, Trifecta 5 (IQR 4-8) mmHg; P = 0.04], effective orifice area (EOA) [2.5 (IQR 2.2-2.7), 2.1 (IQR 1.7-2.3) and 2.6 (IQR 2.3-2.8), respectively; P = 0.02] and EOA index [1.22 (IQR 1.11-1.32), 1.02 (IQR 0.89-1.14) and 1.31 (IQR 1.00-1.42), respectively; P = 0.03]; in each case, Trifecta had better haemodynamics compared with Magna Ease. With exercise, significant differences between groups were evident in peak velocity at 50 watts and peak exercise; mean gradient at 25 watts, 50 watts and maximal exercise; and EOA at 25 watts and at peak exercise; all with haemodynamic superiority of Trifecta compared with Magna Ease. There were no statistically significant differences between Trifecta and Freestyle haemodynamics at rest or with exercise. CONCLUSIONS: In a prospective, randomized study comparing haemodynamics after Freestyle, Magna Ease and Trifecta, all three valves exhibited good haemodynamics at rest and with exercise. There were small but significant differences between groups, with favourable haemodynamics associated with Trifecta compared to Magna Ease, and no significant differences between Trifecta and Freestyle. The Trifecta valve appears to offer haemodynamics similar to a stentless valve without the technical complexity of stentless valve implantation. CLINICALTRIALSGOV IDENTIFIER: NCT01635244. PMID- 26819294 TI - It is not safe unless everyone is aware. PMID- 26819293 TI - Surgical ventricular restoration plus mitral valve repair in patients with ischaemic heart failure: risk factors for early and mid-term outcomes?. AB - OBJECTIVES: To assess the early and mid-term outcomes and related predictors in a consecutive series of patients who underwent surgical ventricular restoration (SVR) combined with additional mitral valve (MV) repair. METHODS: From January 2001 to October 2014, 626 patients underwent SVR; of these, 175 (28%, median age 65) had an additional MV repair. Anterior, inferior or diffuse remodelling was present in 124 (71%), 41 (23%) and 10 (6%) patients, respectively. The median ejection fraction was 30%, whereas mitral regurgitation grade was 3.3 +/- 0.8. Multivariable logistic regression and Cox regression analyses were used to identify predictors of early and mid-term mortality. RESULTS: Operative death occurred in 25 patients (14.3%). Independent predictors of early mortality were age, creatinine and ejection fraction score [odds ratio (OR) = 5.1, 95% confidence interval (CI) 2.5-10.3], previous stroke (OR = 8.0, 95% CI 1.5-44), unstable angina (OR = 8.8, 95% CI 1.5-53) and diffuse remodelling (OR = 5.8, 95% CI 1.02-33). Average follow-up was 42 +/- 37 months. The actuarial survival rate of the whole patient population at 3, 5 and 8 years was 72 +/- 4, 65 +/- 4 and 45 +/- 6%, respectively. Risk factors for late mortality were preoperative creatinine (OR = 2.6, 95% CI 1.5-4.4), previous implantation of cardioverter defibrillator (OR = 4.7, 95% CI 1.6-5.8), whereas the absence of angina at the time of surgery emerged as protective factor (OR = 0.46, 95% CI 0.23-0.89). CONCLUSIONS: MV repair combined with SVR is a complex and challenging procedure that can be performed with acceptable early and mid-term results. Interestingly, angina features predict both early and late outcome, with unstable angina at the time of surgery being a predictor of poor early outcome and the absence of angina at surgery, a predictor of favourable outcome at mid-term follow-up. PMID- 26819295 TI - E-cigarettes: effective cessation tools or public health threat? PMID- 26819297 TI - Pulse oximetry in general practice: an underutilised assessment tool. PMID- 26819296 TI - A phase I study for intravenous autologous mesenchymal stromal cell administration to patients with severe emphysema. AB - BACKGROUND: Mesenchymal stromal cells (MSCs) may reduce inflammation and promote tissue repair in pulmonary emphysema. AIM: To study the safety and feasibility of bone marrow-derived autologous (BM-) MSC intravenous administration to patients with severe emphysema. DESIGN: A phase I, prospective open-label study registered at ClinicalTrials.gov as NCT01306513 Eligible patients had lung volume reduction surgery (LVRS) on two separate occasions. During the first LVRS bone marrow was collected, from which MSCs were isolated and expanded ex vivo After 8 weeks, patients received two autologous MSC infusions 1 week apart, followed by the second LVRS procedure at 3 weeks after the second BM-MSC infusion. METHODS: Up to 3 weeks after the last MSC infusion adverse events were recorded. Using immunohistochemistry and qPCR for analysis of cell and proliferation markers, emphysematous lung tissue obtained during the first surgery was compared with lung tissue obtained after the second surgical session to assess BM-MSC effects. RESULTS: From 10 included patients three were excluded: two did not receive MSCs due to insufficient MSC culture expansion, and one had no second surgery. No adverse events related to MSC infusions occurred and lung tissue showed no fibrotic responses. After LVRS and MSC infusions alveolar septa showed a 3-fold increased expression of the endothelial marker CD31 (P = 0.016). CONCLUSIONS: Autologous MSC treatment in severe emphysema is feasible and safe. The increase in CD31 expression after LVRS and MSC treatment suggests responsiveness of microvascular endothelial cells in the most severely affected parts of the lung. PMID- 26819298 TI - Standardization of cupping therapy may reduce adverse effects. PMID- 26819299 TI - Opportunistic screening for atrial fibrillation in a rural area. AB - INTRODUCTION: Opportunistic screening is an effective means of identifying subjects with Atrial Fibrillation (AF). Previous studies of opportunistic screening have been performed areas with high population density and before the development of novel oral anticoagulant drugs. We performed a study to determine feasibility of AF screening in a predominantly rural, low population density area. METHODS: Over 6 months, subjects 65 years and older were screened by local General Practitioners using radial pulse palpation confirmed by 12 lead Electrocardiogram. Data were recorded electronically and those with newly identified AF were followed up to examine management post diagnosis. RESULTS: In total, 7262 subjects were screened and an irregular pulse was found in 916 (12.6%) of whom 735 (10.1%) had known AF and 55 (0.76%) had newly detected AF. Of these 55 patients with newly documented AF, 28 (50.9%) were women, 38 (69.1%) had hypertension and eight (14.5%) had a smoking history. Mean body mass index in subjects with newly documented AF was 28.9 kg/m(2)(SD 5.6) There was no significant difference in gender mix (P = 0.4), smoking history (P = 0.8) or alcohol history (P = 0.8) with the overall population. Fifty-one (92.7%) subjects had a CHA2DS2VaSC score >= 2 of whom 33 (64.7%) were eventually anticoagulated and nine (17.6%) commenced on Aspirin. The rate of newly identified patients in AF was lower than in previous reported key studies because of a higher rate of subjects with known AF. CONCLUSION: Opportunistic AF screening in a rural environment identified a substantial number of new cases, although less than in previous screening studies. PMID- 26819300 TI - Hypertrophic cranial pachymeningitis and granulomatosis with polyangiitis. PMID- 26819301 TI - E. P. Pope Memorial Award to Dr. Jeremiah T. Saliki. PMID- 26819302 TI - Corrigendum. PMID- 26819303 TI - Generation and Characterization of Monoclonal Antibodies against a Cyclic Variant of Hepatitis C Virus E2 Epitope 412-422. AB - The hepatitis C virus (HCV) E2 envelope glycoprotein is crucial for virus entry into hepatocytes. A conserved region of E2 encompassing amino acids 412 to 423 (epitope I) and containing Trp420, a residue critical for virus entry, is recognized by several broadly neutralizing antibodies. Peptides embodying this epitope I sequence adopt a beta-hairpin conformation when bound to neutralizing monoclonal antibodies (MAbs) AP33 and HCV1. We therefore generated new mouse MAbs that were able to bind to a cyclic peptide containing E2 residues 412 to 422 (C epitope I) but not to the linear counterpart. These MAbs bound to purified E2 with affinities of about 50 nM, but they were unable to neutralize virus infection. Structural analysis of the complex between C-epitope I and one of our MAbs (C2) showed that the Trp420 side chain is largely buried in the combining site and that the Asn417 side chain, which is glycosylated in E2 and solvent exposed in other complexes, is slightly buried upon C2 binding. Also, the orientation of the cyclic peptide in the antibody-combining site is rotated by 180 degrees compared to the orientations of the other complexes. All these structural features, however, do not explain the lack of neutralization activity. This is instead ascribed to the high degree of selectivity of the new MAbs for the cyclic epitope and to their inability to interact with the epitope in more flexible and extended conformations, which recent data suggest play a role in the mechanisms of neutralization escape. IMPORTANCE: Hepatitis C virus (HCV) remains a major health care burden, affecting almost 3% of the global population. The conserved epitope comprising residues 412 to 423 of the viral E2 glycoprotein is a valid vaccine candidate because antibodies recognizing this region exhibit potent neutralizing activity. This epitope adopts a beta-hairpin conformation when bound to neutralizing MAbs. We explored the potential of cyclic peptides mimicking this structure to elicit anti-HCV antibodies. MAbs that specifically recognize a cyclic variant of the epitope bind to soluble E2 with a lower affinity than other blocking antibodies and do not neutralize virus. The structure of the complex between one such MAb and the cyclic epitope, together with new structural data showing the linear peptide bound to neutralizing MAbs in extended conformations, suggests that the epitope displays a conformational flexibility that contributes to neutralization escape. Such features can be of major importance for the design of epitope-based anti-HCV vaccines. PMID- 26819304 TI - Functional Comparison of HBZ and the Related APH-2 Protein Provides Insight into Human T-Cell Leukemia Virus Type 1 Pathogenesis. AB - Human T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) are highly related retroviruses that transform T cells in vitro but have distinct pathological outcomes in vivo. HTLV-1 encodes a protein from the antisense strand of its proviral genome, the HTLV-1 basic leucine zipper factor (HBZ), which inhibits Tax-1-mediated viral transcription and promotes cell proliferation, a high proviral load, and persistence in vivo. In adult T-cell leukemia/lymphoma (ATL) cell lines and patient T cells, hbz is often the only viral gene expressed. The antisense strand of the HTLV-2 proviral genome also encodes a protein termed APH-2. Like HBZ, APH-2 is able to inhibit Tax-2-mediated viral transcription and is detectable in most primary lymphocytes from HTLV-2-infected patients. However, unlike HBZ, the loss of APH-2 in vivo results in increased viral replication and proviral loads, suggesting that HBZ and APH-2 modulate the virus and cellular pathways differently. Herein, we examined the effect of APH-2 on several known HBZ-modulated pathways: NF-kappaB (p65) transactivation, transforming growth factor beta (TGF-beta) signaling, and interferon regulatory factor 1 (IRF-1) transactivation. Like HBZ, APH-2 has the ability to inhibit p65 transactivation. Conversely, HBZ and APH-2 have divergent effects on TGF-beta signaling and IRF-1 transactivation. Quantitative PCR and protein half-life experiments revealed a substantial disparity between HBZ and APH-2 transcript levels and protein stability, respectively. Taken together, our data further elucidate the functional differences between HBZ and APH-2 and how these differences can have profound effects on the survival of infected cells and, ultimately, pathogenesis. IMPORTANCE: Human T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) are highly related retroviruses that have distinct pathological outcomes in infected hosts. Functional comparisons of HTLV-1 and HTLV-2 proteins provide a better understanding about how HTLV-1 infection is associated with disease and HTLV-2 infection is not. The HTLV genome antisense-strand genes hbz and aph-2 are often the only viral genes expressed in HTLV-infected T cells. Previously, our group found that HTLV-1 HBZ and HTLV-2 APH-2 had distinct effects in vivo and hypothesized that the differences in the interactions of HBZ and APH-2 with important cell signaling pathways dictate whether cells undergo proliferation, apoptosis, or senescence. Ultimately, these functional differences may affect how HTLV-1 causes disease but HTLV-2 generally does not. In the current study, we compared the effects of HBZ and APH-2 on several HTLV-relevant cellular pathways, including the TGF-beta signaling, NF-kappaB activation, and IRF-1 transactivation pathways. PMID- 26819305 TI - MicroRNA-33a-5p Modulates Japanese Encephalitis Virus Replication by Targeting Eukaryotic Translation Elongation Factor 1A1. AB - Japanese encephalitis virus (JEV) is a typical mosquito-borne flavivirus responsible for acute encephalitis and meningitis in humans. However, the molecular mechanism for JEV pathogenesis is still unclear. MicroRNAs (miRNAs) are small noncoding RNAs that act as gene regulators. They are directly or indirectly involved in many cellular functions owing to their ability to target mRNAs for degradation or translational repression. However, how cellular miRNAs are regulated and their functions during JEV infection are largely unknown. In the present study, we found that JEV infection downregulated the expression of endogenous cellular miR-33a-5p. Notably, artificially transfecting with miR-33a 5p mimics led to a significant decrease in viral replication, suggesting that miR 33a-5p acts as a negative regulator of JEV replication. A dual-luciferase reporter assay identified eukaryotic translation elongation factor 1A1 (EEF1A1) as one of the miR-33a-5p target genes. Our study further demonstrated that EEF1A1 can interact with the JEV proteins NS3 and NS5 in replicase complex. Through this interaction, EEF1A1 can stabilize the components of viral replicase complex and thus facilitates viral replication during JEV infection. Taken together, these results suggest that miR-33a-5p is downregulated during JEV infection, which contributes to viral replication by increasing the intracellular level of EEF1A1, an interaction partner of JEV NS3 and NS5. This study provides a better understanding of the molecular mechanisms of JEV pathogenesis. IMPORTANCE: MiRNAs are critical regulators of gene expression that utilize sequence complementarity to bind to and modulate the stability or translation efficiency of target mRNAs. Accumulating data suggest that miRNAs regulate a wide variety of molecular mechanisms in the host cells during viral infections. JEV, a neurotropic flavivirus, is one of the major causes of acute encephalitis in humans worldwide. The roles of cellular miRNAs during JEV infections are widely unexplored. The present study explores a novel role of miR-33a-5p as a negative regulator of JEV replication. We found EEF1A1 as a direct target of miR-33a-5p. We also demonstrated that EEF1A1 interacts with and stabilize the components of JEV replicase complex, which positively regulates JEV replication. These findings suggest a new insight into the molecular mechanism of JEV pathogenesis and provide a possible therapeutic entry point for viral encephalitis. PMID- 26819306 TI - Human Cytomegalovirus pTRS1 and pIRS1 Antagonize Protein Kinase R To Facilitate Virus Replication. AB - Human cytomegalovirus (HCMV) counteracts host defenses that otherwise act to limit viral protein synthesis. One such defense is the antiviral kinase protein kinase R (PKR), which inactivates the eukaryotic initiation factor 2 (eIF2) translation initiation factor upon binding to viral double-stranded RNAs. Previously, the viral TRS1 and IRS1 proteins were found to antagonize the antiviral kinase PKR outside the context of HCMV infection, and the expression of either pTRS1 or pIRS1 was shown to be necessary for HCMV replication. In this study, we found that expression of either pTRS1 or pIRS1 is necessary to prevent PKR activation during HCMV infection and that antagonism of PKR is critical for efficient viral replication. Consistent with a previous study, we observed decreased overall levels of protein synthesis, reduced viral protein expression, and diminished virus replication in the absence of both pTRS1 and pIRS1. In addition, both PKR and eIF2alpha were phosphorylated during infection when pTRS1 and pIRS1 were absent. We also found that expression of pTRS1 was both necessary and sufficient to prevent stress granule formation in response to eIF2alpha phosphorylation. Depletion of PKR prevented eIF2alpha phosphorylation, rescued HCMV replication and protein synthesis, and reversed the accumulation of stress granules in infected cells. Infection with an HCMV mutant lacking the pTRS1 PKR binding domain resulted in PKR activation, suggesting that pTRS1 inhibits PKR through a direct interaction. Together our results show that antagonism of PKR by HCMV pTRS1 and pIRS1 is critical for viral protein expression and efficient HCMV replication. IMPORTANCE: To successfully replicate, viruses must counteract host defenses that limit viral protein synthesis. We have identified inhibition of the antiviral kinase PKR by the viral proteins TRS1 and IRS1 and shown that this is a critical step in HCMV replication. Our results suggest that inhibiting pTRS1 and pIRS1 function or restoring PKR activity during infection may be a successful strategy to limit HCMV disease. PMID- 26819307 TI - The L, M, and S Segments of Rift Valley Fever Virus MP-12 Vaccine Independently Contribute to a Temperature-Sensitive Phenotype. AB - Rift Valley fever (RVF) is endemic to Africa, and the mosquito-borne disease is characterized by "abortion storms" in ruminants and by hemorrhagic fever, encephalitis, and blindness in humans. Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) has a tripartite negative-stranded RNA genome (L, M, and S segments). A live-attenuated vaccine for RVF, the MP-12 vaccine, is conditionally licensed for veterinary use in the United States. MP-12 is fully attenuated by the combination of the partially attenuated L, M, and S segments. Temperature sensitivity (ts) limits viral replication at a restrictive temperature and may be involved with viral attenuation. In this study, we aimed to characterize the ts mutations for MP-12. The MP-12 vaccine showed restricted replication at 38 degrees C and replication shutoff (100-fold or greater reduction in virus titer compared to that at 37 degrees C) at 39 degrees C in Vero and MRC-5 cells. Using rZH501 reassortants with either the MP-12 L, M, or S segment, we found that all three segments encode a temperature-sensitive phenotype. However, the ts phenotype of the S segment was weaker than that of the M or L segment. We identified Gn-Y259H, Gc-R1182G, L-V172A, and L-M1244I as major ts mutations for MP-12. The ts mutations in the L segment decreased viral RNA synthesis, while those in the M segment delayed progeny production from infected cells. We also found that a lack of NSs and/or 78kD/NSm protein expression minimally affected the ts phenotype. Our study revealed that MP-12 is a unique vaccine carrying ts mutations in the L, M, and S segments. IMPORTANCE: Rift Valley fever (RVF) is a mosquito-borne viral disease endemic to Africa, characterized by high rates of abortion in ruminants and severe diseases in humans. Vaccination is important to prevent the spread of disease, and a live attenuated MP-12 vaccine is currently the only vaccine with a conditional license in the United States. This study determined the temperature sensitivity (ts) of MP-12 vaccine to understand virologic characteristics. Our study revealed that MP 12 vaccine contains ts mutations independently in the L, M, and S segments and that MP-12 displays a restrictive replication at 38 degrees C. PMID- 26819308 TI - A Hepatitis C Virus Envelope Polymorphism Confers Resistance to Neutralization by Polyclonal Sera and Broadly Neutralizing Monoclonal Antibodies. AB - Hepatitis C virus (HCV) infection is a global health problem, with millions of chronically infected individuals at risk for cirrhosis and hepatocellular carcinoma. HCV vaccine development is vital in the effort toward disease control and eradication, an undertaking aided by an increased understanding of the mechanisms of resistance to broadly neutralizing antibodies (bNAbs). In this study, we identified HCV codons that vary deep in a phylogenetic tree of HCV sequences and showed that a polymorphism at one of these positions renders Bole1a, a computationally derived, ancestral genotype 1a HCV strain, resistant to neutralization by both polyclonal-HCV-infected plasma and multiple broadly neutralizing monoclonal antibodies with unique binding epitopes. This bNAb resistance mutation reduces replicative fitness, which may explain the persistence of both neutralization-sensitive and neutralization-resistant variants in circulating viral strains. This work identifies an important determinant of bNAb resistance in an ancestral, representative HCV genome, which may inform HCV vaccine development. IMPORTANCE: Worldwide, more than 170 million people are infected with hepatitis C virus (HCV), the leading cause of hepatocellular carcinoma and liver transplantation in the United States. Despite recent significant advances in HCV treatment, a vaccine is needed. Control of the HCV pandemic with drug treatment alone is likely to fail due to limited access to treatment, reinfections in high-risk individuals, and the potential for resistance to direct-acting antivirals (DAAs). Broadly neutralizing antibodies (bNAbs) block infection by diverse HCV variants and therefore serve as a useful guide for vaccine development, but our understanding of resistance to bNAbs is incomplete. In this report, we identify a viral polymorphism conferring resistance to neutralization by both polyclonal plasma and broadly neutralizing monoclonal antibodies, which may inform HCV vaccine development. PMID- 26819309 TI - ESCRT-0 Component Hrs Promotes Macropinocytosis of Kaposi's Sarcoma-Associated Herpesvirus in Human Dermal Microvascular Endothelial Cells. AB - Kaposi's sarcoma-associated herpesvirus (KSHV) enters human dermal microvascular endothelial cells (HMVEC-d), its naturalin vivotarget cells, by lipid raft dependent macropinocytosis. The internalized viral envelope fuses with the macropinocytic membrane, and released capsid is transported to the nuclear vicinity, resulting in the nuclear entry of viral DNA. The endosomal sorting complexes required for transport (ESCRT) proteins, which include ESCRT-0, -I, II, and -III, play a central role in endosomal trafficking and sorting of internalized and ubiquitinated receptors. Here, we examined the role of ESCRT-0 component Hrs (hepatocyte growth factor-regulated tyrosine kinase substrate) in KSHV entry into HMVEC-d by macropinocytosis. Knockdown of Hrs by short hairpin RNA (shRNA) transduction resulted in significant decreases in KSHV entry and viral gene expression. Immunofluorescence analysis (IFA) and plasma membrane isolation and proximity ligation assay (PLA) demonstrated the translocation of Hrs from the cytosol to the plasma membrane of infected cells and association with alpha-actinin-4. In addition, infection induced the plasma membrane translocation and activation of the serine/threonine kinase ROCK1, a downstream target of the RhoA GTPase. Hrs knockdown reduced these associations, suggesting that the recruitment of ROCK1 is an Hrs-mediated event. Interaction between Hrs and ROCK1 is essential for the ROCK1-induced phosphorylation of NHE1 (Na(+)/H(+)exchanger 1), which is involved in the regulation of intracellular pH. Thus, our studies demonstrate the plasma membrane association of ESCRT protein Hrs during macropinocytosis and suggest that KSHV entry requires both Hrs- and ROCK1-dependent mechanisms and that ROCK1-mediated phosphorylation of NHE1 and pH change is an essential event required for the macropinocytosis of KSHV. IMPORTANCE: Macropinocytosis is the major entry pathway of KSHV in human dermal microvascular endothelial cells, the natural target cells of KSHV. Although the role of ESCRT protein Hrs has been extensively studied with respect to endosomal movement and sorting of ubiquitinated proteins into lysosomes, its function in macropinocytosis is not known. In the present study, we demonstrate for the first time that upon KSHV infection, the endogenous Hrs localizes to the plasma membrane and the membrane-associated Hrs facilitates assembly of signaling molecules, macropinocytosis, and virus entry. Hrs recruits ROCK1 to the membrane, which is required for the activation of NHE1 and an increase in submembranous intracellular pH occurring during macropinocytosis. These studies demonstrate that the localization of Hrs from the cytosol to the plasma membrane is important for coupling membrane dynamics to the cytosolic signaling events during macropinocytosis of KSHV. PMID- 26819310 TI - Chimeric Filoviruses for Identification and Characterization of Monoclonal Antibodies. AB - Recent experiments suggest that some glycoprotein (GP)-specific monoclonal antibodies (MAbs) can protect experimental animals against the filovirus Ebola virus (EBOV). There is a need for isolation of MAbs capable of neutralizing multiple filoviruses. Antibody neutralization assays for filoviruses frequently use surrogate systems such as the rhabdovirus vesicular stomatitis Indiana virus (VSV), lentiviruses or gammaretroviruses with their envelope proteins replaced with EBOV GP or pseudotyped with EBOV GP. It is optimal for both screening and in depth characterization of newly identified neutralizing MAbs to generate recombinant filoviruses that express a reporter fluorescent protein in order to more easily monitor and quantify the infection. Our study showed that unlike neutralization-sensitive chimeric VSV, authentic filoviruses are highly resistant to neutralization by MAbs. We used reverse genetics techniques to replace EBOV GP with its counterpart from the heterologous filoviruses Bundibugyo virus (BDBV), Sudan virus, and even Marburg virus and Lloviu virus, which belong to the heterologous genera in the filovirus family. This work resulted in generation of multiple chimeric filoviruses, demonstrating the ability of filoviruses to tolerate swapping of the envelope protein. The sensitivity of chimeric filoviruses to neutralizing MAbs was similar to that of authentic biologically derived filoviruses with the same GP. Moreover, disabling the expression of the secreted GP (sGP) resulted in an increased susceptibility of an engineered virus to the BDBV52 MAb isolated from a BDBV survivor, suggesting a role for sGP in evasion of antibody neutralization in the context of a human filovirus infection. IMPORTANCE: The study demonstrated that chimeric rhabdoviruses in which G protein is replaced with filovirus GP, widely used as surrogate targets for characterization of filovirus neutralizing antibodies, do not accurately predict the ability of antibodies to neutralize authentic filoviruses, which appeared to be resistant to neutralization. However, a recombinant EBOV expressing a fluorescent protein tolerated swapping of GP with counterparts from heterologous filoviruses, allowing high-throughput screening of B cell lines to isolate MAbs of any filovirus specificity. Human MAb BDBV52, which was isolated from a survivor of BDBV infection, was capable of partially neutralizing a chimeric EBOV carrying BDBV GP in which expression of sGP was disabled. In contrast, the parental virus expressing sGP was resistant to the MAb. Thus, the ability of filoviruses to tolerate swapping of GP can be used for identification of neutralizing MAbs specific to any filovirus and for the characterization of MAb specificity and mechanism of action. PMID- 26819311 TI - Spatiotemporal Analysis of the Genetic Diversity of Seal Influenza A(H10N7) Virus, Northwestern Europe. AB - Influenza A viruses are major pathogens for humans, domestic animals, and wildlife, and these viruses occasionally cross the species barrier. In spring 2014, increased mortality of harbor seals (Phoca vitulina), associated with infection with an influenza A(H10N7) virus, was reported in Sweden and Denmark. Within a few months, this virus spread to seals of the coastal waters of Germany and the Netherlands, causing the death of thousands of animals. Genetic analysis of the hemagglutinin (HA) and neuraminidase (NA) genes of this seal influenza A(H10N7) virus revealed that it was most closely related to various avian influenza A(H10N7) viruses. The collection of samples from infected seals during the course of the outbreak provided a unique opportunity to follow the adaptation of the avian virus to its new seal host. Sequence data for samples collected from 41 different seals from four different countries between April 2014 and January 2015 were obtained by Sanger sequencing and next-generation sequencing to describe the molecular epidemiology of the seal influenza A(H10N7) virus. The majority of sequence variation occurred in the HA gene, and some mutations corresponded to amino acid changes not found in H10 viruses isolated from Eurasian birds. Also, sequence variation in the HA gene was greater at the beginning than at the end of the epidemic, when a number of the mutations observed earlier had been fixed. These results imply that when an avian influenza virus jumps the species barrier from birds to seals, amino acid changes in HA may occur rapidly and are important for virus adaptation to its new mammalian host. IMPORTANCE: Influenza A viruses are major pathogens for humans, domestic animals, and wildlife. In addition to the continuous circulation of influenza A viruses among various host species, cross-species transmission of influenza A viruses occurs occasionally. Wild waterfowl and shorebirds are the main reservoir for most influenza A virus subtypes, and spillover of influenza A viruses from birds to humans or other mammalian species may result in major outbreaks. In the present study, various sequencing methods were used to elucidate the genetic changes that occurred after the introduction and subsequent spread of an avian influenza A(H10N7) virus among harbor seals of northwestern Europe by use of various samples collected during the outbreak. Such detailed knowledge of genetic changes necessary for introduction and adaptation of avian influenza A viruses to mammalian hosts is important for a rapid risk assessment of such viruses soon after they cross the species barrier. PMID- 26819312 TI - Suppression of Type I Interferon Production by Human T-Cell Leukemia Virus Type 1 Oncoprotein Tax through Inhibition of IRF3 Phosphorylation. AB - Infection with human T-cell leukemia virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and tropical spastic paraparesis. Type I interferons (IFNs) are key effectors of the innate antiviral response, and IFN-alpha combined with the nucleoside reverse transcriptase inhibitor zidovudine is considered the standard first-line therapy for ATL. HTLV-1 oncoprotein Tax is known to suppress innate IFN production and response but the underlying mechanisms remain to be fully established. In this study, we report on the suppression of type I IFN production by HTLV-1 Tax through interaction with and inhibition of TBK1 kinase that phosphorylates IRF3. Induced transcription of IFN-beta was severely impaired in HTLV-1-transformed ATL cells and freshly infected T lymphocytes. The ability to suppress IRF3 activation was ascribed to Tax. The expression of Tax alone sufficiently repressed the induction of IFN production by RIG-I plus PACT, cGAMP synthase plus STING, TBK1, IKKepsilon, IRF3, and IRF7, but not by IRF3-5D, a dominant-active phosphomimetic mutant. This suggests that Tax perturbs IFN production at the step of IRF3 phosphorylation. Tax mutants deficient for CREB or NF-kappaB activation were fully competent in the suppression of IFN production. Coimmunoprecipitation experiments confirmed the association of Tax with TBK1, IKKepsilon, STING, and IRF3.In vitrokinase assay indicated an inhibitory effect of Tax on TBK1-mediated phosphorylation of IRF3. Taken together, our findings suggested a new mechanism by which HTLV-1 oncoprotein Tax circumvents the production of type I IFNs in infected cells. Our findings have implications in therapeutic intervention of ATL. IMPORTANCE: Human T-cell leukemia virus type 1 (HTLV-1) is the cause of adult T-cell leukemia (ATL), an aggressive and fatal blood cancer, as well as another chronic disabling disease of the spinal cord. Treatments are unsatisfactory, and options are limited. A combination of antiviral cellular protein alpha interferon and zidovudine, which is an inhibitor of a viral enzyme called reverse transcriptase, has been recommended as the standard first-line therapy for ATL. Exactly how HTLV-1 interacts with the cellular machinery for interferon production and action is not well understood. Our work sheds light on the mechanism of action for the inhibition of interferon production by an HTLV-1 oncogenic protein called Tax. Our findings might help to improve interferon-based anti-HTLV-1 and anti-ATL therapy. PMID- 26819313 TI - Primary B Lymphocytes Infected with Kaposi's Sarcoma-Associated Herpesvirus Can Be Expanded In Vitro and Are Recognized by LANA-Specific CD4+ T Cells. AB - Kaposi's sarcoma-associated herpesvirus (KSHV) has tropism for B lymphocytes, in which it establishes latency, and can also cause lymphoproliferative disorders of these cells manifesting as primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). T cell immunity is vital for the control of KSHV infection and disease; however, few models of B lymphocyte infection exist to study immune recognition of such cells. Here, we developed a model of B lymphocyte infection with KSHV in which infected tonsillar B lymphocytes were expanded by providing mitogenic stimuli and then challenged with KSHV-specific CD4(+)T cells. The infected cells expressed viral proteins found in PELs, namely, LANA and viral IRF3 (vIRF3), albeit at lower levels, with similar patterns of gene expression for the major latency, viral interleukin 6 (vIL-6), and vIRF3 transcripts. Despite low-level expression of open reading frame 50 (ORF50), transcripts for the immune evasion genes K3 and K5 were detected, with some downregulation of cell surface-expressed CD86 and ICAM. The vast majority of infected lymphocytes expressed IgM heavy chains with Iglambda light chains, recapitulating the features seen in infected cells in MCD. We assessed the ability of the infected lymphocytes to be targeted by a panel of major histocompatibility complex (MHC) class II-matched CD4(+)T cells and found that LANA-specific T cells restricted to different epitopes recognized these infected cells. Given that at least some KSHV latent antigens are thought to be poor targets for CD8(+)T cells, we suggest that CD4(+)T cells are potentially important effectors for thein vivocontrol of KSHV-infected B lymphocytes. IMPORTANCE: KSHV establishes a latent reservoir within B lymphocytes, but few models exist to study KSHV-infected B cells other than the transformed PEL cell lines, which have likely accrued mutations during the transformation process. We developed a model of KSHV-infected primary B lymphocytes that recapitulates features seen in PEL and MCD by gene expression and cell phenotype analysis, allowing the study of T cell recognition of these cells. Challenge of KSHV infected B cells with CD4(+)T cells specific for LANA, a protein expressed in all KSHV-infected cells and malignanciesin vivo, showed that these effectors could efficiently recognize such targets. Given that the virus expresses immune evasion genes or uses proteins with intrinsic properties, such as LANA, that minimize epitope recognition by CD8(+)T cells, CD4(+)T cell immunity to KSHV may be important for maintaining the virus-host balance. PMID- 26819314 TI - Induction of Epstein-Barr Virus Oncoprotein LMP1 by Transcription Factors AP-2 and Early B Cell Factor. AB - Latent membrane protein 1 (LMP1) is a major oncogene essential for primary B cell transformation by Epstein-Barr virus (EBV). Previous studies suggested that some transcription factors, such as PU.1, RBP-Jkappa, NF-kappaB, and STAT, are involved in this expression, but the underlying mechanism is unclear. Here, we identified binding sites for PAX5, AP-2, and EBF in the proximal LMP1 promoter (ED-L1p). We first confirmed the significance of PU.1 and POU domain transcription factor binding for activation of the promoter in latency III. We then focused on the transcription factors AP-2 and early B cell factor (EBF). Interestingly, among the three AP-2-binding sites in the LMP1 promoter, two motifs were also bound by EBF. Overexpression, knockdown, and mutagenesis in the context of the viral genome indicated that AP-2 plays an important role in LMP1 expression in latency II in epithelial cells. In latency III B cells, on the other hand, the B cell-specific transcription factor EBF binds to the ED-L1p and activates LMP1 transcription from the promoter. IMPORTANCE: Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is crucial for B cell transformation and oncogenesis of other EBV-related malignancies, such as nasopharyngeal carcinoma and T/NK lymphoma. Its expression is largely dependent on the cell type or condition, and some transcription factors have been implicated in its regulation. However, these previous reports evaluated the significance of specific factors mostly by reporter assay. In this study, we prepared point-mutated EBV at the binding sites of such transcription factors and confirmed the importance of AP-2, EBF, PU.1, and POU domain factors. Our results will provide insight into the transcriptional regulation of the major oncogene LMP1. PMID- 26819316 TI - Microfluidic assay for precise measurements of mouse, rat, and human neutrophil chemotaxis in whole-blood droplets. AB - Animal models of human disease differ in innate immune responses to stress, pathogens, or injury. Precise neutrophil phenotype measurements could facilitate interspecies comparisons. However, such phenotype comparisons could not be performed accurately with the use of current assays, as they require the separation of neutrophils from blood using species-specific protocols, and they introduce distinct artifacts. Here, we report a microfluidic technology that enables robust characterization of neutrophil migratory phenotypes in a manner independent of the donor species and performed directly in a droplet of whole blood. The assay relies on the particular ability of neutrophils to deform actively during chemotaxis through microscale channels that block the advance of other blood cells. Neutrophil migration is measured directly in blood, in the presence of other blood cells and serum factors. Our measurements reveal important differences among migration counts, velocity, and directionality among neutrophils from 2 common mouse strains, rats, and humans. PMID- 26819315 TI - Methylthioadenosine (MTA) Regulates Liver Cells Proteome and Methylproteome: Implications in Liver Biology and Disease. AB - Methylthioadenosine phosphorylase (MTAP), a key enzyme in the adenine and methionine salvage pathways, catalyzes the hydrolysis of methylthioadenosine (MTA), a compound suggested to affect pivotal cellular processes in part through the regulation of protein methylation. MTAP is expressed in a wide range of cell types and tissues, and its deletion is common to cancer cells and in liver injury. The aim of this study was to investigate the proteome and methyl proteome alterations triggered by MTAP deficiency in liver cells to define novel regulatory mechanisms that may explain the pathogenic processes of liver diseases. iTRAQ analysis resulted in the identification of 216 differential proteins (p < 0.05) that suggest deregulation of cellular pathways as those mediated by ERK or NFkappaB. R-methyl proteome analysis led to the identification of 74 differentially methylated proteins between SK-Hep1 and SK-Hep1+ cells, including 116 new methylation sites. Restoring normal MTA levels in SK-Hep1+ cells parallels the specific methylation of 56 proteins, including KRT8, TGF, and CTF8A, which provides a novel regulatory mechanism of their activity with potential implications in carcinogenesis. Inhibition of RNA-binding proteins methylation is especially relevant upon accumulation of MTA. As an example, methylation of quaking protein in Arg(242) and Arg(256) in SK-Hep1+ cells may play a pivotal role in the regulation of its activity as indicated by the up regulation of its target protein p27(kip1) The phenotype associated with a MTAP deficiency was further verified in the liver of MTAP+/- mice. Our data support that MTAP deficiency leads to MTA accumulation and deregulation of central cellular pathways, increasing proliferation and decreasing the susceptibility to chemotherapeutic drugs, which involves differential protein methylation. Data are available via ProteomeXchange with identifier PXD002957 (http://www.ebi.ac.uk/pride/archive/projects/PXD002957). PMID- 26819317 TI - The E3 ubiquitin ligase RNF144B is LPS-inducible in human, but not mouse, macrophages and promotes inducible IL-1beta expression. AB - Differences in human and mouse immune responses may partly reflect species specific adaptations and can provide important insights into human immunity. In this study, we show that RNF144B, which encodes an E3 ubiquitin ligase, was lipopolysaccharide-inducible in primary human macrophages and in human macrophage like THP-1 cells. In contrast, Rnf144b was not lipopolysaccharide-inducible in several mouse cell populations, including primary macrophages from C57BL/6 and BALB/c mice and RAW264.7 macrophages. Similarly, Rnf144b was not up-regulated by infection of C57BL/6 mice with Escherichia coli Although the human and mouse RNF144B genes have conserved transcription start sites, cap analysis of gene expression data confirmed that the RNF144B promoter directs transcription in human but not mouse macrophages. The human and mouse RNF144B genes are controlled by highly conserved TATA-containing promoters, but subtle differences in transcription factor binding sites may account for differential regulation. Using gene silencing, we showed that RNF144B is necessary for priming of inflammasome responses in primary human macrophages. Specifically, RNF144B promotes lipopolysaccharide-inducible IL-1b mRNA expression but does not regulate expression of several other lipopolysaccharide-inducible cytokines (e.g., interleukin-10, interferon-gamma) or affect expression of inflammasome components or substrates (e.g., procaspase-1, pro-interleukin-18). Our findings thus revealed a species-specific regulatory mechanism for selective inflammasome priming in human macrophages. PMID- 26819318 TI - Distinct CCR7 glycosylation pattern shapes receptor signaling and endocytosis to modulate chemotactic responses. AB - The homeostatic chemokines CCL19 and CCL21 and their common cognate chemokine receptor CCR7 orchestrate immune cell trafficking by eliciting distinct signaling pathways. Here, we demonstrate that human CCR7 is N-glycosylated on 2 specific residues in the N terminus and the third extracellular loop. Conceptually, CCR7 glycosylation adds steric hindrance to the receptor N terminus and extracellular loop 3, acting as a "swinging door" to regulate receptor sensitivity and cell migration. We found that freshly isolated human B cells, as well as expanded T cells, but not naive T cells, express highly sialylated CCR7. Moreover, we identified that human dendritic cells imprint T cell migration toward CCR7 ligands by secreting enzymes that deglycosylate CCR7, thereby boosting CCR7 signaling on T cells, permitting enhanced T cell locomotion, while simultaneously decreasing receptor endocytosis. In addition, dendritic cells proteolytically convert immobilized CCL21 to a soluble form that is more potent in triggering chemotactic movement and does not desensitize the receptor. Furthermore, we demonstrate that soluble CCL21 functionally resembles neither the CCL19 nor the CCL21 phenotype but acts as a chemokine with unique features. Thus, we advance the concept of dendritic cell-dependent generation of micromilieus and lymph node conditioning by demonstrating a novel layer of CCR7 regulation through CCR7 sialylation. In summary, we demonstrate that leukocyte subsets express distinct patterns of CCR7 sialylation that contribute to receptor signaling and fine tuning chemotactic responses. PMID- 26819319 TI - Survival of residual neutrophils and accelerated myelopoiesis limit the efficacy of antibody-mediated depletion of Ly-6G+ cells in tumor-bearing mice. AB - Expansion of Ly-6G(+) myeloid cells has been reported in most murine cancer models. However, divergent findings exist regarding the role and effect of these cells on host immunity and tumor progression. Antibody-mediated depletion of Ly 6G(+) cells is a common technique to assess the in vivo relevance of these cells. Interpretation of results crucially depends on the efficacy and course of depletion. We established murine head and neck cancer models and analyzed the efficacy of antibody-mediated depletion by flow cytometry, conventional histology, and intravital imaging with a novel Ly-6G-transgenic mouse model. The first phase of depletion was characterized by effective elimination of Ly-6G(+) cells from the peripheral blood. Nevertheless, viable, resistant cells were found to reside in the tumor tissue and spleen. This peripheral depletion phase was associated with high systemic levels of granulocyte colony-stimulating factor and KC and enhanced splenic production of Ly-6G(+) cells. Even under sustained treatment with either alphaGr-1 or alphaLy-6G antibodies, peripheral blood depletion ended after approximately 1 wk and was followed by reappearance of immature Ly-6G(+) cells with an immunoregulatory phenotype. Reappearance of these depletion-resistant immature cells was enhanced in tumor-bearing, compared with naive, control mice. Collectively, our data suggest that depletion of Ly-6G(+) myeloid cells in tumor-bearing mice is counteracted by the persistence of intratumoral cells, enhanced extramedullary granulopoiesis, and accelerated reappearance of immature cells. Hence, extensive monitoring of in vivo kinetics and tissue distribution of Ly-6G(+) cells is required in depletion studies. PMID- 26819320 TI - Decidual macrophages: key regulators of vascular remodeling in human pregnancy. AB - Successful remodeling of the uterine spiral arteries is essential for a complication-free pregnancy and is best described in terms of its morphologic features. The molecular mediators and cellular sources of spiral artery remodeling are not known, although a role for uterine leukocytes has been proposed. Immunohistochemical assessment of placental bed biopsies demonstrated uterine NK cells, macrophages, and T lymphocytes in the wall and adventitia of spiral arteries at different stages of remodeling, regardless of the presence of extravillous trophoblast cells. Leukocytes were more prevalent in vessel adventitia than wall, and macrophages were the most abundant leukocyte population. Macrophages, separated from early pregnancy decidua, did not alter extravillous trophoblast cells invasion or vascular smooth muscle cell organization or differentiation status but did induce extracellular matrix breakdown (reduced immunostaining of laminin, P = 0.05; fibronectin, P = 0.02) and were able to phagocytose apoptotic vascular smooth muscle cells. Decidual macrophages were shown to secrete a wide range of cytokines (IL-1beta, -2, -4, 5, -6, -8, -10, and -13 and TNF-alpha), proteases (matrix metalloproteinase-1, 2, -7, -9, and -10), and angiogenic growth factors (angiogenin, keratinocyte growth factor, fibroblast growth factor B, vascular endothelial growth factor A, and angiopoietin-1 and -2). We conclude that spiral artery remodeling involves the coordinated activity of a range of cell types, including extravillous trophoblast cells, decidual uterine NK cells, and macrophages in a carefully, spatiotemporally regulated manner. PMID- 26819322 TI - Pulsus paradoxus due to a tumorous mass constricting the heart. PMID- 26819323 TI - Multimodality assessment of spontaneous haemostasis of left ventricular free wall rupture after myocardial infarction. PMID- 26819324 TI - Coronary artery anomaly and evaluation by FFR computed tomography. PMID- 26819325 TI - Assessment of cardiac sympathetic innervation with (123)I-mIBG SPECT comes to life: need for standardization! PMID- 26819321 TI - Biological Nanomotors with a Revolution, Linear, or Rotation Motion Mechanism. AB - The ubiquitous biological nanomotors were classified into two categories in the past: linear and rotation motors. In 2013, a third type of biomotor, revolution without rotation (http://rnanano.osu.edu/movie.html), was discovered and found to be widespread among bacteria, eukaryotic viruses, and double-stranded DNA (dsDNA) bacteriophages. This review focuses on recent findings about various aspects of motors, including chirality, stoichiometry, channel size, entropy, conformational change, and energy usage rate, in a variety of well-studied motors, including FoF1 ATPase, helicases, viral dsDNA-packaging motors, bacterial chromosome translocases, myosin, kinesin, and dynein. In particular, dsDNA translocases are used to illustrate how these features relate to the motion mechanism and how nature elegantly evolved a revolution mechanism to avoid coiling and tangling during lengthy dsDNA genome transportation in cell division. Motor chirality and channel size are two factors that distinguish rotation motors from revolution motors. Rotation motors use right-handed channels to drive the right-handed dsDNA, similar to the way a nut drives the bolt with threads in same orientation; revolution motors use left-handed motor channels to revolve the right-handed dsDNA. Rotation motors use small channels (<2 nm in diameter) for the close contact of the channel wall with single-stranded DNA (ssDNA) or the 2-nm dsDNA bolt; revolution motors use larger channels (>3 nm) with room for the bolt to revolve. Binding and hydrolysis of ATP are linked to different conformational entropy changes in the motor that lead to altered affinity for the substrate and allow work to be done, for example, helicase unwinding of DNA or translocase directional movement of DNA. PMID- 26819326 TI - 'The ICECAP-SCM tells you more about what I'm going through': A think-aloud study measuring quality of life among patients receiving supportive and palliative care. AB - BACKGROUND: The ICECAP-Supportive Care Measure is a self-complete questionnaire developed to aid economic evaluation of supportive care interventions. AIM: To determine the feasibility of completing ICECAP-Supportive Care Measure alongside EQ-5D-5L and ICECAP-A (generic measures used in economic evaluation) among patients receiving hospice care, close persons and healthcare professionals. DESIGN: Participants were asked to 'think aloud' while completing ICECAP Supportive Care Measure and two other generic measures used in economic evaluation, EQ-5D-5L and ICECAP-A, and then participate in a semi-structured interview. From verbatim transcripts, five raters identified the frequency of errors in comprehension, retrieval, judgement and response. Qualitative data were analysed using constant comparison. SETTING/PARTICIPANTS: Eligible patients were identified from one UK hospice by a research nurse. Close persons and healthcare professionals were identified by the patient. In all, 72 semi-structured interviews were conducted with patients (n = 33), close persons (n = 22) and healthcare professionals (n = 17). RESULTS: Patients and close persons reported that the ICECAP-Supportive Care Measure was most appropriate for measuring their quality of life. It appeared more meaningful, easier to complete and had fewest errors (3.9% among patients, 4.5% among close persons) compared to EQ-5D-5L (9.7% among patients, 5.5% among close persons). Healthcare professionals acknowledged the value of the ICECAP-Supportive Care Measure but had fewer errors in completing the EQ-5D-5L (3.5% versus 6.7%). They found it easier to complete because it focuses on observable health states. CONCLUSIONS: The ICECAP Supportive Care Measure is feasible to use and perceived as appropriate for evaluating palliative care interventions. Healthcare professionals with limited knowledge of the patient who act as proxy completers may find the measure difficult to complete. PMID- 26819327 TI - Reducing inequalities in care for patients with non-malignant diseases: Insights from a realist evaluation of an integrated palliative care pathway. AB - BACKGROUND: The need for palliative care is growing internationally with an increasing prevalence of non-malignant diseases. The integrated care pathway was implemented in primary care by multidisciplinary teams from 2009 in a locality in the North East of England. Fourteen general practitioner practices provided data for the study. AIM: To find whether, how, and under what circumstances palliative care registrations are made for patients with non-malignant diseases in primary care. DESIGN: General practitioner practice data were analysed statistically and qualitative data were collected from health care professionals and members of relevant organisations. FINDINGS: A mixed-effects logistic model indicated a significant difference beyond the 0.1% level (p < 0.001) in registrations between the malignant and non-malignant groups in 2011, with an odds ratio of 0.09 (=exp( 2.4266)), indicating that patients in the non-malignant group are around 11 times (1/0.09) less likely to be registered than patients in the malignant group. However, patients with non-malignant diseases were significantly more likely to be registered in 2012 than in 2011 with an odds ratio of 1.46, significant beyond the 1% level. Qualitative analyses indicate that health care professionals find registering patients with non-malignant diseases stressful, yet feel that their confidence in treating this population is increasing. CONCLUSION: The integrated care pathway began to enable the reduction in inequalities in care by identifying, registering and managing an increasing number of palliative patients with non-malignant diseases. Consensual and inclusive definitions of palliative care were developed in order to legitimise the registration of such patients. PMID- 26819328 TI - Peptide production and secretion in GLUTag, NCI-H716, and STC-1 cells: a comparison to native L-cells. AB - GLUTag, NCI-H716, and STC-1 are cell lines that are widely used to study mechanisms underlying secretion of glucagon-like peptide-1 (GLP-1), but the extent to which they resemble native L-cells is unknown. We used validated immunoassays for 14 different hormones to analyze peptide content (lysis samples; n = 9 from different passage numbers) or peptide secretion in response to buffer (baseline), and after stimulation with 50 mM KCl or 10 mM glucose + 10 uM forskolin/3-isobutyl-1-methylxanthine (n = 6 also different passage numbers). All cell lines produced and processed proglucagon into GLP-1, GLP-2, glicentin, and oxyntomodulin in a pattern (prohormone convertase (PC)1/3 dependent) similar to that described for human gut. All three cell lines showed basal secretion of GLP 1 and GLP-2, which increased after stimulation. In contrast to freshly isolated murine L-cells, all cell lines also expressed PC2 and secreted large amounts of pancreatic glucagon. Neurotensin and somatostatin storage was low and secretion was not consistently increased by stimulation. STC-1 cells released more glucose dependent insulinotropic polypeptide than GLP-1 at baseline (P < 0.01) and KCl elevated its secretion (P < 0.05). Peptide YY, which normally co-localizes with GLP-1 in distal L-cells, was not detected in any of the cell lines. GLUTag and STC-1 cells also expressed vasoactive intestinal peptide, but none expressed pancreatic polypeptide or insulin. GLUTag contained and secreted large amounts of CCK, while NCI-H716 did not store this peptide and STC-1 contained low amounts. Our results show that hormone production in cell line models of the L-cell has limited similarity to the natural L-cells. PMID- 26819329 TI - Paramedical risk framing during field referral of acute stroke and S-T elevation myocardial infarction patients. AB - Field referral of emergency ambulance patients by paramedics on a widespread basis is a relatively new aspect of paramedicine. Its implementation involves a significant revision to paramedics' clinical responsibilities and level of interaction with medical specialists. Using grounded theory methodology, this qualitative study uses interviews with paramedics from Ontario, Canada, to explore the framing of risk associated with these referrals in the context of caring for patients with two high-stakes medical conditions: acute stroke and S-T elevation myocardial infarction. The results outline how paramedics have incorporated risk framing into their practice. PMID- 26819330 TI - An Expanded Reverse Line Blot Hybridization Protocol for the Simultaneous Detection of Numerous Tick-Borne Pathogens in North America. AB - Due to an increasing diversity of bacterial pathogens known to be transmitted by hard ticks (Acari: Ixodidae) in North America, a comprehensive assay is needed to detect and differentiate among these numerous tick-borne pathogens. We describe an expanded protocol using a combination of multiplex polymerase chain reaction and reverse line blot hybridization to detect a greater diversity of infectious agents than were previously detectable. Ten novel oligonucleotide probes, either individually or in concert, enabled or enhanced identification of six Borrelia species, three Rickettsia species, and one Ehrlichia species. Simultaneous detection of these numerous tick-borne pathogens can advance surveillance efforts and improve accuracy of detection and, thus, reporting. PMID- 26819331 TI - 7-(2-Thienyl)-7-Deazaadenosine (AB61), a New Potent Nucleoside Cytostatic with a Complex Mode of Action. AB - 7-(2-Thienyl)-7-deazaadenosine (AB61) showed nanomolar cytotoxic activities against various cancer cell lines but only mild (micromolar) activities against normal fibroblasts. The selectivity of AB61 was found to be due to inefficient phosphorylation of AB61 in normal fibroblasts. The phosphorylation of AB61 in the leukemic CCRF-CEM cell line proceeds well and it was shown that AB61 is incorporated into both DNA and RNA, preferentially as a ribonucleotide. It was further confirmed that a triphosphate of AB61 is a substrate for both RNA and DNA polymerases in enzymatic assays. Gene expression analysis suggests that AB61 affects DNA damage pathways and protein translation/folding machinery. Indeed, formation of large 53BP1 foci was observed in nuclei of AB61-treated U2OS-GFP 53BP1 cells indicating DNA damage. Random incorporation of AB61 into RNA blocked its translation in an in vitro assay and reduction of reporter protein expression was also observed in mice after 4-hour treatment with AB61. AB61 also significantly reduced tumor volume in mice bearing SK-OV-3, BT-549, and HT-29 xenografts. The results indicate that AB61 is a promising compound with unique mechanism of action and deserves further development as an anticancer agent. Mol Cancer Ther; 15(5); 922-37. (c)2016 AACR. PMID- 26819332 TI - DNA double-strand break repair: a theoretical framework and its application. AB - DNA double-strand breaks (DSBs) are formed as a result of genotoxic insults, such as exogenous ionizing radiation, and are among the most serious types of DNA damage. One of the earliest molecular responses following DSB formation is the phosphorylation of the histone H2AX, giving rise to gammaH2AX. Many copies of gammaH2AX are generated at DSBs and can be detected in vitro as foci using well established immuno-histochemical methods. It has previously been shown that anti gammaH2AX antibodies, modified by the addition of the cell-penetrating peptide TAT and a fluorescent or radionuclide label, can be used to visualize and quantify DSBs in vivo. Moreover, when labelled with a high amount of the short range, Auger electron-emitting radioisotope, (111)In, the amount of DNA damage within a cell can be increased, leading to cell death. In this report, we develop a mathematical model that describes how molecular processes at individual sites of DNA damage give rise to quantifiable foci. Equations that describe stochastic mean behaviours at individual DSB sites are derived and parametrized using population-scale, time-series measurements from two different cancer cell lines. The model is used to examine two case studies in which the introduction of an antibody (anti-gammaH2AX-TAT) that targets a key component in the DSB repair pathway influences system behaviour. We investigate: (i) how the interaction between anti-gammaH2AX-TAT and gammaH2AX effects the kinetics of H2AX phosphorylation and DSB repair and (ii) model behaviour when the anti-gammaH2AX antibody is labelled with Auger electron-emitting (111)In and can thus instigate additional DNA damage. This work supports the conclusion that DSB kinetics are largely unaffected by the introduction of the anti-gammaH2AX antibody, a result that has been validated experimentally, and hence the hypothesis that the use of anti-gammaH2AX antibody to quantify DSBs does not violate the image tracer principle. Moreover, it provides a novel model of DNA damage accumulation in the presence of Auger electron-emitting (111)In that is supported qualitatively by the available experimental data. PMID- 26819333 TI - Stretch-induced network reconfiguration of collagen fibres in the human facet capsular ligament. AB - Biomaterials can display complex spatial patterns of cellular responses to external forces. Revealing and predicting the role of these patterns in material failure require an understanding of the statistical dependencies between spatially distributed changes in a cell's local biomechanical environment, including altered collagen fibre kinematics in the extracellular matrix. Here, we develop and apply a novel extension of network science methods to investigate how excessive tensile stretch of the human cervical facet capsular ligament (FCL), a common source of chronic neck pain, affects the local reorganization of collagen fibres. We define collagen alignment networks based on similarity in fibre alignment angles measured by quantitative polarized light imaging. We quantify the reorganization of these networks following macroscopic loading by describing the dynamic reconfiguration of network communities, regions of the material that display similar fibre alignment angles. Alterations in community structure occur smoothly over time, indicating coordinated adaptation of fibres to loading. Moreover, flexibility, a measure of network reconfiguration, tracks the loss of FCL's mechanical integrity at the onset of anomalous realignment (AR) and regions of AR display altered community structure. These findings use novel network-based techniques to explain abnormal collagen fibre reorganization, a dynamic and coordinated multivariate process underlying tissue failure. PMID- 26819334 TI - Non-dimensional physics of pulsatile cardiovascular networks and energy efficiency. AB - In Nature, there exist a variety of cardiovascular circulation networks in which the energetic ventricular load has both steady and pulsatile components. Steady load is related to the mean cardiac output (CO) and the haemodynamic resistance of the peripheral vascular system. On the other hand, the pulsatile load is determined by the simultaneous pressure and flow waveforms at the ventricular outlet, which in turn are governed through arterial wave dynamics (transmission) and pulse decay characteristics (windkessel effect). Both the steady and pulsatile contributions of the haemodynamic power load are critical for characterizing/comparing disease states and for predicting the performance of cardiovascular devices. However, haemodynamic performance parameters vary significantly from subject to subject because of body size, heart rate and subject-specific CO. Therefore, a 'normalized' energy dissipation index, as a function of the 'non-dimensional' physical parameters that govern the circulation networks, is needed for comparative/integrative biological studies and clinical decision-making. In this paper, a complete network-independent non-dimensional formulation that incorporates pulsatile flow regimes is developed. Mechanical design variables of cardiovascular flow systems are identified and the Buckingham Pi theorem is formally applied to obtain the corresponding non-dimensional scaling parameter sets. Two scaling approaches are considered to address both the lumped parameter networks and the distributed circulation components. The validity of these non-dimensional number sets is tested extensively through the existing empirical allometric scaling laws of circulation systems. Additional validation studies are performed using a parametric numerical arterial model that represents the transmission and windkessel characteristics, which are adjusted to represent different body sizes and non-dimensional haemodynamic states. Simulations demonstrate that the proposed non-dimensional indices are independent of body size for healthy conditions, but are sensitive to deviations caused by off-design disease states that alter the energetic load. Sensitivity simulations are used to identify the relationship between pulsatile power loss and non dimensional characteristics, and optimal operational states are computed. PMID- 26819335 TI - Ordering structured populations in multiplayer cooperation games. AB - Spatial structure greatly affects the evolution of cooperation. While in two player games the condition for cooperation to evolve depends on a single structure coefficient, in multiplayer games the condition might depend on several structure coefficients, making it difficult to compare different population structures. We propose a solution to this issue by introducing two simple ways of ordering population structures: the containment order and the volume order. If population structure S1 is greater than population structure S1 in the containment or the volume order, then S1 can be considered a stronger promoter of cooperation. We provide conditions for establishing the containment order, give general results on the volume order, and illustrate our theory by comparing different models of spatial games and associated update rules. Our results hold for a large class of population structures and can be easily applied to specific cases once the structure coefficients have been calculated or estimated. PMID- 26819337 TI - Inequality Issues in Stem Cell Medicine. PMID- 26819336 TI - Large-scale signatures of unconsciousness are consistent with a departure from critical dynamics. AB - Loss of cortical integration and changes in the dynamics of electrophysiological brain signals characterize the transition from wakefulness towards unconsciousness. In this study, we arrive at a basic model explaining these observations based on the theory of phase transitions in complex systems. We studied the link between spatial and temporal correlations of large-scale brain activity recorded with functional magnetic resonance imaging during wakefulness, propofol-induced sedation and loss of consciousness and during the subsequent recovery. We observed that during unconsciousness activity in frontothalamic regions exhibited a reduction of long-range temporal correlations and a departure of functional connectivity from anatomical constraints. A model of a system exhibiting a phase transition reproduced our findings, as well as the diminished sensitivity of the cortex to external perturbations during unconsciousness. This framework unifies different observations about brain activity during unconsciousness and predicts that the principles we identified are universal and independent from its causes. PMID- 26819338 TI - Naive Induced Pluripotent Stem Cells Generated From beta-Thalassemia Fibroblasts Allow Efficient Gene Correction With CRISPR/Cas9. PMID- 26819344 TI - Does cardiac rhythm monitoring in patients with elevated troponin levels lead to changes in management? AB - BACKGROUND: We sought to identify the frequency of arrhythmias in patients with elevated cardiac troponin levels and without ST-segment elevation myocardial infarction or a primary arrhythmia, and to determine whether detection of an arrhythmia leads to management changes. METHODS: A review of 1381 consecutive patients admitted from the emergency department for rhythm monitoring with an elevated cardiac troponin T (cTnT) level was performed. Patients admitted to an intensive care unit and those with an initial primary arrhythmia were excluded. Troponin values were obtained on admission, at 3 hours and at 6 hours. Electronic medical records and all rhythm recordings were reviewed for documentation of an arrhythmia and any changes in management. RESULTS: An arrhythmia was detected in 26% of the 330 patients who met the inclusion criteria. Those with arrhythmias had higher rates of coronary artery disease and prior percutaneous coronary intervention ( p = 0.02 and p = 0.01, respectively). Those with arrhythmias had higher mean cTnT values compared to those without arrhythmias ( p = 0.02 at 3 hours and p = 0.006 at 6 hours) even after controlling for a discharge diagnosis of acute coronary syndrome. Changes in management in response to the detection of arrhythmias were infrequent (6.3%) and usually included only changes in medication doses. CONCLUSIONS: Patients admitted with an elevated cTnT level to a non-intensive care unit rhythm-monitored bed without ST-segment elevation myocardial infarction or primary arrhythmia have a high incidence of arrhythmias; however, changes in management are infrequent. PMID- 26819339 TI - Prevalence of reproductive tract infections and the predictive value of girls' symptom-based reporting: findings from a cross-sectional survey in rural western Kenya. AB - OBJECTIVES: Reproductive tract infections (RTIs), including sexually acquired, among adolescent girls is a public health concern, but few studies have measured prevalence in low-middle-income countries. The objective of this study was to examine prevalence in rural schoolgirls in Kenya against their reported symptoms. METHODS: In 2013, a survey was conducted in 542 adolescent schoolgirls aged 14-17 years who were enrolled in a menstrual feasibility study. Vaginal self-swabbing was conducted after girls were interviewed face-to-face by trained nurses on symptoms. The prevalence of girls with symptoms and laboratory-confirmed infections, and the sensitivity, specificity, positive and negative predictive values of symptoms compared with laboratory results, were calculated. RESULTS: Of 515 girls agreeing to self-swab, 510 answered symptom questions. A quarter (24%) reported one or more symptoms; most commonly vaginal discharge (11%), pain (9%) or itching (4%). Laboratory tests confirmed 28% of girls had one or more RTI. Prevalence rose with age; among girls aged 16-17 years, 33% had infections. Bacterial vaginosis was the most common (18%), followed by Candida albicans (9%), Chlamydia trachomatis (3%), Trichomonas vaginalis (3%) and Neisseria gonorrhoeae (1%). Reported symptoms had a low sensitivity and positive predictive value. Three-quarters of girls with bacterial vaginosis and C. albicans, and 50% with T. vaginalis were asymptomatic. CONCLUSIONS: There is a high prevalence of adolescent schoolgirls with RTI in rural Kenya. Public efforts are required to identify and treat infections among girls to reduce longer-term sequelae but poor reliability of symptom reporting minimises utility of symptom-based diagnosis in this population. TRIAL REGISTRATION NUMBER: ISRCTN17486946. PMID- 26819345 TI - Role of Increased n-acetylaspartate Levels in Cancer. AB - BACKGROUND: The clinical and biological effects of metabolic alterations in cancer are not fully understood. METHODS: In high-grade serous ovarian cancer (HGSOC) samples (n = 101), over 170 metabolites were profiled and compared with normal ovarian tissues (n = 15). To determine NAT8L gene expression across different cancer types, we analyzed the RNA expression of cancer types using RNASeqV2 data available from the open access The Cancer Genome Atlas (TCGA) website (http://www.cbioportal.org/public-portal/). Using NAT8L siRNA, molecular techniques and histological analysis, we determined cancer cell viability, proliferation, apoptosis, and tumor growth in in vitro and in vivo (n = 6-10 mice/group) settings. Data were analyzed with the Student's t test and Kaplan Meier analysis. Statistical tests were two-sided. RESULTS: Patients with high levels of tumoral NAA and its biosynthetic enzyme, aspartate N-acetyltransferase (NAT8L), had worse overall survival than patients with low levels of NAA and NAT8L. The overall survival duration of patients with higher-than-median NAA levels (3.6 years) was lower than that of patients with lower-than-median NAA levels (5.1 years, P = .03). High NAT8L gene expression in other cancers (melanoma, renal cell, breast, colon, and uterine cancers) was associated with worse overall survival. NAT8L silencing reduced cancer cell viability (HEYA8: control siRNA 90.61% +/- 2.53, NAT8L siRNA 39.43% +/- 3.00, P < .001; A2780: control siRNA 90.59% +/- 2.53, NAT8L siRNA 7.44% +/- 1.71, P < .001) and proliferation (HEYA8: control siRNA 74.83% +/- 0.92, NAT8L siRNA 55.70% +/- 1.54, P < .001; A2780: control siRNA 50.17% +/- 4.13, NAT8L siRNA 26.52% +/- 3.70, P < .001), which was rescued by addition of NAA. In orthotopic mouse models (ovarian cancer and melanoma), NAT8L silencing reduced tumor growth statistically significantly (A2780: control siRNA 0.52 g +/- 0.15, NAT8L siRNA 0.08 g +/- 0.17, P < .001; HEYA8: control siRNA 0.79 g +/- 0.42, NAT8L siRNA 0.24 g +/- 0.18, P = .008, A375-SM: control siRNA 0.55 g +/- 0.22, NAT8L siRNA 0.21 g +/- 0.17 g, P = .001). NAT8L silencing downregulated the anti-apoptotic pathway, which was mediated through FOXM1. CONCLUSION: These findings indicate that the NAA pathway has a prominent role in promoting tumor growth and represents a valuable target for anticancer therapy.Altered energy metabolism is a hallmark of cancer (1). Proliferating cancer cells have much greater metabolic requirements than nonproliferating differentiated cells (2,3). Moreover, altered cancer metabolism elevates unique metabolic intermediates, which can promote cancer survival and progression (4,5). Furthermore, emerging evidence suggests that proliferating cancer cells exploit alternative metabolic pathways to meet their high demand for energy and to accumulate biomass (6-8). PMID- 26819346 TI - Resveratrol and its methoxy-derivatives as modulators of DNA damage induced by ionising radiation. AB - Various naturally occurring stilbene-like compounds that are related to resveratrol (RSV) possess some of the beneficial effects of the parent molecule and provide even further benefits. Therefore, a series of methoxylated analogues of RSV were prepared with the aim of increasing antitumour and proapoptotic activity. In a previous article, we studied two methoxy-derivatives, pterostilbene (PTERO) and trimethoxystilbene (TRIMETHOXY), in which the first was formed by the substitution of two hydroxyl groups with two methoxy groups (trans 3,5-dimethoxy-4'-hydroxystilbene) and the second was formed by the replacement of all three OH groups with methoxy groups (trans-3,5,4'-trimethoxystilbene). Both methoxy-derivatives showed stronger antioxidant activity when compared with RSV. In the present article, we focused on the analysis of the ability of RSV and its two methoxylated derivatives to protect proliferating non-tumoural cells from the damage induced by ionising radiation (IR). First we showed that the methoxy derivatives, contrary to their parental compound, are unable to affect topoisomerase enzyme and consequently are not clastogenic per se Second we showed that both PTERO and TRIMETHOXY more efficiently reduce the chromosome damage induced by IR. Furthermore, TRIMETHOXY, but not PTERO, causes a delay in cell proliferation, particularly in mitosis progression increasing the number of cells in metaphase at the expense of prophases and ana/telophases. PMID- 26819349 TI - The Psychoanalytic Mode of Thought and its Application To the Non-Normative Analysis of Sexuality and Gender. AB - Freud's psychoanalytic mode of thought, especially as interpreted by William Grossman, functions as an inherently non-normative means of analyzing both the psychic life of the individual and various historical and cultural phenomena. Application of this mode of thought to particular characterizations of gender and sexuality makes possible an essential critique of trait psychology and static formulations of human development, as restricting both clinical practice and theory building. An exploration of the complexities of sexuality and gender in gay men shows how Freud's insistence on variability lends conceptual power at the intersection of classical psychoanalysis, with its problematic history, and the many clinical and theoretical manifestations of contemporary psychoanalysis. The non-normative psychoanalytic mode of thought developed by Freud must be integrated with more recent formulations about gender and sexuality in order to conduct a psychoanalysis. PMID- 26819348 TI - Empirically based Suggested Insights into the Concept of False-Self Defense: Contributions From a Study on Normalization of Children With Disabilities. AB - The concept of the false self has been used widely in psychoanalytic theory and practice but seldom in empirical research. In this empirically based study, elevated features of false-self defense were hypothetically associated with risk factors attendant on processes of rehabilitation and integration of children with disabilities, processes that encourage adaptation of the child to the able-bodied environment. Self-report questionnaires and in-depth interviews were conducted with 88 deaf and hard-of-hearing students and a comparison group of 88 hearing counterparts. Results demonstrate that despite the important contribution of rehabilitation and integration to the well-being of these children, these efforts may put the child at risk of increased use of the false-self defense. The empirical findings suggest two general theoretical conclusions: (1) The Winnicottian concept of the environment, usually confined to the parent-child relationship, can be understood more broadly as including cultural, social, and rehabilitational variables that both influence the parent-child relationship and operate independently of it. (2) The monolithic conceptualization of the false self may be more accurately unpacked to reveal two distinct subtypes: the compliant and the split false self. PMID- 26819347 TI - Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy. AB - The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy. PMID- 26819350 TI - Lymphedema. PMID- 26819353 TI - Social Activities, Socioeconomic Factors, and Overweight Status Among Middle-Aged and Older Korean Adults: A Cross-Sectional Study. AB - This study aims to investigate the relationship between social activities and overweight among middle-aged and older adults. This study used data from the 2008 Korean Longitudinal Study of Aging which included a total of 8157 adults. We divided body mass index into 2 groups: normal weight and overweight. Multivariable logistic regression analysis was used to identify the association between social activities and overweight. For males, frequency of meetings with neighbors (1-3 times a week) was associated with being less overweight. Middle aged adults who met with neighbors 1 to 3 times a week were less likely being overweight than those with once a year meeting frequency. On the contrary, social activity participation is related with high risk of overweight especially in the female and older adults. Our results suggest that social activity participation and social support needs to be taken into consideration when dealing with being overweight. PMID- 26819355 TI - Pamidronate in complex regional pain syndrome: effective therapy in CRPS. PMID- 26819354 TI - Comorbidity in severe asthma requiring systemic corticosteroid therapy: cross sectional data from the Optimum Patient Care Research Database and the British Thoracic Difficult Asthma Registry. AB - OBJECTIVE: To determine the prevalence of systemic corticosteroid-induced morbidity in severe asthma. DESIGN: Cross-sectional observational study. SETTING: The primary care Optimum Patient Care Research Database and the British Thoracic Society Difficult Asthma Registry. PARTICIPANTS: Optimum Patient Care Research Database (7195 subjects in three age- and gender-matched groups)-severe asthma (Global Initiative for Asthma (GINA) treatment step 5 with four or more prescriptions/year of oral corticosteroids, n=808), mild/moderate asthma (GINA treatment step 2/3, n=3975) and non-asthma controls (n=2412). 770 subjects with severe asthma from the British Thoracic Society Difficult Asthma Registry (442 receiving daily oral corticosteroids to maintain disease control). MAIN OUTCOME MEASURES: Prevalence rates of morbidities associated with systemic steroid exposure were evaluated and reported separately for each group. RESULTS: 748/808 (93%) subjects with severe asthma had one or more condition linked to systemic corticosteroid exposure (mild/moderate asthma 3109/3975 (78%), non-asthma controls 1548/2412 (64%); p<0.001 for severe asthma versus non-asthma controls). Compared with mild/moderate asthma, morbidity rates for severe asthma were significantly higher for conditions associated with systemic steroid exposure (type II diabetes 10% vs 7%, OR=1.46 (95% CI 1.11 to 1.91), p<0.01; osteoporosis 16% vs 4%, OR=5.23, (95% CI 3.97 to 6.89), p<0.001; dyspeptic disorders (including gastric/duodenal ulceration) 65% vs 34%, OR=3.99, (95% CI 3.37 to 4.72), p<0.001; cataracts 9% vs 5%, OR=1.89, (95% CI 1.39 to 2.56), p<0.001). In the British Thoracic Society Difficult Asthma Registry similar prevalence rates were found, although, additionally, high rates of osteopenia (35%) and obstructive sleep apnoea (11%) were identified. CONCLUSIONS: Oral corticosteroid related adverse events are common in severe asthma. New treatments which reduce exposure to oral corticosteroids may reduce the prevalence of these conditions and this should be considered in cost-effectiveness analyses of these new treatments. PMID- 26819357 TI - Surprisingly few psychological problems and diabetes-related distress in patients with poor glycaemic control. AB - OBJECTIVE: Poor glycaemic control is an undesirable, but frequently encountered problem in diabetes. Reasons for not achieving optimal glycaemic control are not yet clear. A common belief is that psychological factors contribute importantly. This study compared general psychological problems and diabetes-related distress between patients with persistently poor glycaemic control to patients with optimal glycaemic control. METHODS: Patients from an outpatient clinic with type 1 or type 2 diabetes with a mean HbA1c >= 86 mmol/mol (>= 10%) over two consecutive years (poor-control, n = 32) and those with diabetes and a mean HbA1c <= 53 mmol/mol (<= 7%) over two consecutive years (optimal-control, n = 53) were studied. Clinical characteristics were obtained from the medical records. Psychological characteristics were investigated cross-sectionally using questionnaires. RESULTS: Patients in the poor-control group had a higher BMI compared with the optimal-control group. Self- reported previous anxiety was more prevalent in the poor-control group (34 versus 9%). All other mean test scores and proportions of subjects above cut-off levels were similar in the two groups. CONCLUSIONS: Patients with diabetes and persistently poor glycaemic control have surprisingly few psychological problems and diabetes-related emotional distress. It seems that people with diabetes do not see persistent poor glycaemic control as a problem. PMID- 26819356 TI - Safety and long-term effects of renal denervation: Rationale and design of the Dutch registry. AB - BACKGROUND: Percutaneous renal denervation (RDN) has recently been introduced as a treatment for therapy-resistant hypertension. Also, it has been suggested that RDN may be beneficial for other conditions characterised by increased sympathetic nerve activity. There are still many uncertainties with regard to efficacy, safety, predictors for success and long-term effects. To answer these important questions, we initiated a Dutch RDN registry aiming to collect data from all RDN procedures performed in the Netherlands. METHODS: The Dutch RDN registry is an ongoing investigator-initiated, prospective, multicentre cohort study. Twenty-six Dutch hospitals agreed to participate in this registry. All patients who undergo RDN, regardless of the clinical indication or device that is used, will be included. Data are currently being collected on eligibility and screening, treatment and follow-up. RESULTS: Procedures have been performed since August 2010. At present, data from 306 patients have been entered into the database. The main indication for RDN was hypertension (n = 302, 99%). Patients had a mean office blood pressure of 177/100 (+/-29/16) mmHg with a median use of three (range 0-8) blood pressure lowering drugs. Mean 24-hour blood pressure before RDN was 157/93 (+/-18/13) mmHg. RDN was performed with different devices, with the SimplicityTM catheter currently used most frequently. CONCLUSION: Here we report on the rationale and design of the Dutch RDN registry. Enrolment in this investigator-initiated study is ongoing. We present baseline characteristics of the first 306 participants. PMID- 26819358 TI - Perinatal outcomes in gestational diabetes in relation to ethnicity in the Netherlands. AB - BACKGROUND: The influence of ethnicity in women with gestational diabetes in relation to maternal, pregnancy and neonatal outcome is not well defined. AIM: To compare the perinatal outcome in women with gestational diabetes between different ethnic groups reflecting the multi-ethnic population in the Netherlands. METHODS: Patients with gestational diabetes (n = 388) who visited the multidisciplinary outpatient clinic for Diabetes Care and Obstetrics of the Sint Franciscus Gasthuis in Rotterdam between 2010 and 2013 were included. Ethnicity was distinguished into six groups: Moroccan (n = 100); Turkish (n = 43); Caucasian (n = 146); Suriname-Creole (n = 23); Suriname-Hindu (n = 32); and Miscellaneous (n = 44). RESULTS: Caucasians were the largest group with gestational diabetes (37.7%), followed by Moroccans (25.8%). Body mass index before pregnancy was highest in Surinamese-Creole women, followed by Turks and Moroccans (p < 0.001). Gravidity and parity were highest in Moroccans. Gravidity was lowest in Surinamese-Hindus and parity was lowest in Caucasians (p < 0.001). There was also a remarkable, significant difference in the mode of delivery between the ethnicities with the lowest number of normal deliveries in Caucasians and the highest in Moroccans (p = 0.03). Assisted delivery occurred most frequently in Caucasian women, although there was no difference in the frequency of caesarean sections. Birth weight was the only neonatal parameter showing significant differences between the ethnicities, with the highest birth weight for Moroccan children and the lowest for Surinamese children (3542 g vs. 3200; p = 0.001). CONCLUSION: This study did not show major differences in maternal or neonatal complications, however there are significant disparities in (percentile) birth weight and mode of delivery across the different ethnic groups. PMID- 26819359 TI - Pamidronate effect compared with a steroid on complex regional pain syndrome type I: Pilot randomised trial. AB - OBJECTIVES: This study aims to compare the effectiveness of a bisphosphonate (pamidronate) and a steroid (prednisolone) in complex regional pain syndrome (CRPS) type I during four weeks of follow-up in hemiplegic stroke patients. METHODS: Twenty-one hemiplegic stroke patients with CRPS type I were enrolled in the study. Patients were randomly assigned to receive either intravenous pamidronate (n = 11; total cumulative dose of 180 mg) or oral prednisolone (n = 10). Subjective pain and hand oedema (circumference of the middle finger, CMF, and the wrist, CW) were measured at baseline and at one, two and four weeks after the end of treatment. RESULTS: Both groups showed significant improvement in subjective pain VAS scores at 1-week follow-up and this effect was maintained until 4-week follow-up. Time-by-group interactions were not significant at 4-week follow-up. The reduction of the CMF observed at 1-week follow-up in both groups was maintained until 4-week follow-up in the steroid group, but until 2-week follow-up in the pamidronate group. A significant change in CW was observed at 4 week follow-up in the pamidronate group. There were no significant adverse effects in either treatment group during the follow-up period. CONCLUSIONS: Intravenous pamidronate therapy was safe, well tolerated and appeared as effective as a steroid for pain control for post-stroke CRPS. However, this result should be interpreted with caution, since it included a relatively small number of patients. Further larger controlled studies followed over a longer period are needed to validate these findings and to determine clinical treatment standards. PMID- 26819360 TI - Fatal hyperammonaemia due to late-onset ornithine transcarbamylase deficiency. AB - In this case report we describe a 67-year-old male, admitted to the ICU with pneumonia who unexpectedly developed a fatal coma due to hyperammonaemia. At postmortem the diagnosis late-onset ornithine transcarbamylase deficiency was made. The non-specific clinical presentation, the rapid deterioration and incidentally the fatal outcome all underline the importance of recognition and knowledge of this genetic disorder. Several measures to treat and prevent potentially fatal episodes of hyperammonaemia are available, if only the disorder is recognised in time. In retrospect, several clues to the diagnosis were available in this fatal case, such as voluntary protein avoidance, as well as several male family members who died at a young age of an unknown cause. After his death, two daughters were discovered to be carriers of an OTC gene mutation, as well as his infant grandson. We emphasise the importance of obtaining ammonia levels in all patients with unexplained coma, seizures or cerebral oedema, irrespective of their age, especially in patients in the ICU or in an otherwise catabolic state. PMID- 26819361 TI - An unexpected pulmonary bystander. AB - A 30-year-old man from Eritrea was admitted with a pulmonary bacterial abscess. Unexpectedly, histopathology of the resected lobe also revealed an infection with Schistosoma mansoni with surrounding granulomatous tissue and fibrosis. Patients from endemic areas are often asymptomatic with blood eosinophilia being the only diagnostic clue. Early recognition is important as ongoing fibrosing inflammation may result in organ damage. PMID- 26819362 TI - Amyloid A amyloidosis secondary to hyper IgD syndrome and response to IL-1 blockage therapy. AB - A 62-year-old woman with a history of genetically confirmed hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) was admitted because of chronic diarrhoea. During admission she developed a rapidly progressive nephrotic syndrome. Reactive amyloid A (AA) amyloidosis was confirmed after colonic and renal biopsy which showed deposition of amyloid. After initial treatment with high-dosed corticosteroids, therapy was switched to anakinra, an IL-1 receptor antagonist, but her symptoms persisted. After cessation of anakinra, a marked exacerbation of the intestinal symptoms was noted. Nine months after the initial diagnosis of reactive amyloidosis without any amelioration of the symptoms and a decreasing quality of life, our patient declined further treatment and died soon after. This case demonstrates that AA amyloidosis does occur in patients with HIDS and can present with intestinal symptoms and proteinuria. Once amyloidosis is diagnosed the goal of treatment is to prevent further complications. In this case report we give an overview of previous cases with amyloidosis complicating HIDS with the treatments received and propose a step-up treatment plan for future cases. PMID- 26819363 TI - Not your average filling defect. PMID- 26819365 TI - Acute erythema of the face after methotrexate. PMID- 26819367 TI - Hepatitis E virus infection among blood donors in the South Caribbean: is screening warranted? PMID- 26819368 TI - Rabies prophylaxis for travellers. PMID- 26819369 TI - Reply to letter to the editor of H.T. Gozdas. PMID- 26819370 TI - Treatment restrictions and empirical antibiotic treatment of community-acquired pneumonia in elderly patients. PMID- 26819371 TI - Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens. AB - The antigenicity of cells is demarcated by the peptides bound by their Human Leucocyte Antigen (HLA) molecules. Through this antigen presentation, T cell specificity response is controlled. As a fraction of the expressed mutated peptides is presented on the HLA, these neo-epitopes could be immunogenic. Such neo-antigens have recently been identified through screening for predicted mutated peptides, using synthetic peptides or ones expressed from minigenes, combined with screening of patient tumor-infiltrating lymphocytes (TILs). Here we present a time and cost-effective method that combines whole-exome sequencing analysis with HLA peptidome mass spectrometry, to identify neo-antigens in a melanoma patient. Of the 1,019 amino acid changes identified through exome sequencing, two were confirmed by mass spectrometry to be presented by the cells. We then synthesized peptides and evaluated the two mutated neo-antigens for reactivity with autologous bulk TILs, and found that one yielded mutant-specific T-cell response. Our results demonstrate that this method can be used for immune response prediction and promise to provide an alternative approach for identifying immunogenic neo-epitopes in cancer. PMID- 26819372 TI - PDIP46 (DNA polymerase delta interacting protein 46) is an activating factor for human DNA polymerase delta. AB - PDIP46 (SKAR, POLDIP3) was discovered through its interaction with the p50 subunit of human DNA polymerase delta (Pol delta). Its functions in DNA replication are unknown. PDIP46 associates with Pol delta in cell extracts both by immunochemical and protein separation methods, as well as by ChIP analyses. PDIP46 also interacts with PCNA via multiple copies of a novel PCNA binding motif, the APIMs (AlkB homologue-2 PCNA-Interacting Motif). Sites for both p50 and PCNA binding were mapped to the N-terminal region containing the APIMs. Functional assays for the effects of PDIP46 on Pol delta activity on singly primed ssM13 DNA templates revealed that it is a novel and potent activator of Pol delta. The effects of PDIP46 on Pol delta in primer extension, strand displacement and synthesis through simple hairpin structures reveal a mechanism where PDIP46 facilitates Pol delta4 synthesis through regions of secondary structure on complex templates. In addition, evidence was obtained that PDIP46 is also capable of exerting its effects by a direct interaction with Pol delta, independent of PCNA. Mutation of the Pol delta and PCNA binding region resulted in a loss of PDIP46 functions. These studies support the view that PDIP46 is a novel accessory protein for Pol delta that is involved in cellular DNA replication. This raises the possibility that altered expression of PDIP46 or its mutation may affect Pol delta functions in vivo, and thereby be a nexus for altered genomic stability. PMID- 26819374 TI - Evidence for Intramyocardial Disruption of Lipid Metabolism and Increased Myocardial Ketone Utilization in Advanced Human Heart Failure. AB - BACKGROUND: The failing human heart is characterized by metabolic abnormalities, but these defects remains incompletely understood. In animal models of heart failure there is a switch from a predominance of fatty acid utilization to the more oxygen-sparing carbohydrate metabolism. Recent studies have reported decreases in myocardial lipid content, but the inclusion of diabetic and nondiabetic patients obscures the distinction of adaptations to metabolic derangements from adaptations to heart failure per se. METHODS AND RESULTS: We performed both unbiased and targeted myocardial lipid surveys using liquid chromatography-mass spectroscopy in nondiabetic, lean, predominantly nonischemic, advanced heart failure patients at the time of heart transplantation or left ventricular assist device implantation. We identified significantly decreased concentrations of the majority of myocardial lipid intermediates, including long chain acylcarnitines, the primary subset of energetic lipid substrate for mitochondrial fatty acid oxidation. We report for the first time significantly reduced levels of intermediate and anaplerotic acyl-coenzyme A (CoA) species incorporated into the Krebs cycle, whereas the myocardial concentration of acetyl CoA was significantly increased in end-stage heart failure. In contrast, we observed an increased abundance of ketogenic beta-hydroxybutyryl-CoA, in association with increased myocardial utilization of beta-hydroxybutyrate. We observed a significant increase in the expression of the gene encoding succinyl CoA:3-oxoacid-CoA transferase, the rate-limiting enzyme for myocardial oxidation of beta-hydroxybutyrate and acetoacetate. CONCLUSIONS: These findings indicate increased ketone utilization in the severely failing human heart independent of diabetes mellitus, and they support the role of ketone bodies as an alternative fuel and myocardial ketone oxidation as a key metabolic adaptation in the failing human heart. PMID- 26819373 TI - Myeloid-Epithelial-Reproductive Receptor Tyrosine Kinase and Milk Fat Globule Epidermal Growth Factor 8 Coordinately Improve Remodeling After Myocardial Infarction via Local Delivery of Vascular Endothelial Growth Factor. AB - BACKGROUND: In infarcted heart, improper clearance of dying cells by activated neighboring phagocytes may precipitate the transition to heart failure. We analyzed the coordinated role of 2 major mediators of efferocytosis, the myeloid epithelial-reproductive protein tyrosine kinase (Mertk) and the milk fat globule epidermal growth factor (Mfge8), in directing cardiac remodeling by skewing the inflammatory response after myocardial infarction. METHODS AND RESULTS: We generated double-deficient mice for Mertk and Mfge8 (Mertk(-/-)/Mfge8(-/-)) and challenged them with acute coronary ligature. Compared with wild-type, Mertk deficient (Mertk(-/-)), or Mfge8-deficient (Mfge8(-/-)) animals, Mertk(-/ )/Mfge8(-/-) mice displayed greater alteration in cardiac function and remodeling. Mertk and Mfge8 were expressed mainly by cardiac Ly6C(High and Low) monocytes and macrophages. In parallel, Mertk(-/-)/Mfge8(-/-) bone marrow chimeras manifested increased accumulation of apoptotic cells, enhanced fibrotic area, and larger infarct size, as well as reduced angiogenesis. We found that the abrogation of efferocytosis affected neither the ability of circulating monocytes to infiltrate cardiac tissue nor the number of resident Ly6C(High) and Ly6C(How) monocytes/macrophages populating the infarcted milieu. In contrast, combined Mertk and Mfge8 deficiency in Ly6C(High)/Ly6C(Low) monocytes/macrophages either obtained from in vitro differentiation of bone marrow cells or isolated from infarcted hearts altered their capacity of efferocytosis and subsequently blunted vascular endothelial growth factor A (VEGFA) release. Using LysMCre(+)/VEGFA(fl/fl) mice, we further identified an important role for myeloid derived VEGFA in improving cardiac function and angiogenesis. CONCLUSIONS: After myocardial infarction, Mertk- and Mfge8-expressing monocyte/macrophages synergistically engage the clearance of injured cardiomyocytes, favoring the secretion of VEGFA to locally repair the dysfunctional heart. PMID- 26819375 TI - Ketones Step to the Plate: A Game Changer for Metabolic Remodeling in Heart Failure? PMID- 26819377 TI - The application of multi-objective optimization method for activated sludge process: a review. AB - The activated sludge process (ASP) is the most generally applied biological wastewater treatment approach. Depending on the design and specific application, activated sludge wastewater treatment plants (WWTPs) can achieve biological nitrogen (N) and phosphorus (P) removal, besides the removal of organic carbon substances. However, the effluent N and P limits are getting tighter because of increased emphasis on environmental protection, and the needs for energy conservation as well as the operational reliability. Therefore, the balance between treatment performance and cost becomes a critical issue for the operations of WWTPs, which necessitates a multi-objective optimization (MOO). Recent studies in this field have shown promise in utilizing MOO to address the multiple conflicting criteria (i.e. effluent quality, operation cost, operation stability), including studying the ASP models that are primarily responsible for the process, and developing the method of MOO in the wastewater treatment process, which facilitates better optimization of process performance. Based on a better understanding of the application of MOO for ASP, a comprehensive review is conducted to offer a clear vision of the advances, and potential areas for future research are also proposed in the field. PMID- 26819378 TI - Contaminants of emerging concern in reverse osmosis brine concentrate from indirect/direct water reuse applications. AB - Water shortage is becoming more common due to droughts and global population increases resulting in the increasing popularity of water reuse to create new water sources. Reverse osmosis (RO) membrane systems are popular in these applications since they can produce drinking water quality effluent. Unfortunately, RO systems have the drawback of generating concentrate streams that contain contaminants rejected by the membrane including chemicals of emerging concern (CECs). CECs are chemicals such as hormones, steroids, pesticides, pharmaceuticals, and personal care products that are used for their intended purpose and then released into wastewater. CECs are believed to be detrimental to aquatic wildlife health and pose an unknown human health risk. This research gathered the existing knowledge on CEC presence in concentrate, available proven concentrate treatment methods, their CEC removal abilities, and current CEC regulations. It was found that 127 CECs have been measured in RO concentrate with 100 being detected at least once. The most potent treatment process available is UV/H2O2 as it offers the highest removal rates for the widest range of chemicals. The less expensive process of ozone/biologically activated carbon offers slightly lower removal abilities. This comprehensive report will provide the groundwork for better understanding, regulating and treating concentrate stream CECs. PMID- 26819376 TI - The Failing Heart Relies on Ketone Bodies as a Fuel. AB - BACKGROUND: Significant evidence indicates that the failing heart is energy starved. During the development of heart failure, the capacity of the heart to utilize fatty acids, the chief fuel, is diminished. Identification of alternate pathways for myocardial fuel oxidation could unveil novel strategies to treat heart failure. METHODS AND RESULTS: Quantitative mitochondrial proteomics was used to identify energy metabolic derangements that occur during the development of cardiac hypertrophy and heart failure in well-defined mouse models. As expected, the amounts of proteins involved in fatty acid utilization were downregulated in myocardial samples from the failing heart. Conversely, expression of beta-hydroxybutyrate dehydrogenase 1, a key enzyme in the ketone oxidation pathway, was increased in the heart failure samples. Studies of relative oxidation in an isolated heart preparation using ex vivo nuclear magnetic resonance combined with targeted quantitative myocardial metabolomic profiling using mass spectrometry revealed that the hypertrophied and failing heart shifts to oxidizing ketone bodies as a fuel source in the context of reduced capacity to oxidize fatty acids. Distinct myocardial metabolomic signatures of ketone oxidation were identified. CONCLUSIONS: These results indicate that the hypertrophied and failing heart shifts to ketone bodies as a significant fuel source for oxidative ATP production. Specific metabolite biosignatures of in vivo cardiac ketone utilization were identified. Future studies aimed at determining whether this fuel shift is adaptive or maladaptive could unveil new therapeutic strategies for heart failure. PMID- 26819379 TI - Drivers for and against municipal wastewater recycling: a review. AB - The reclamation, treatment and reuse of municipal wastewater can provide important environmental benefits. In this paper, 25 studies on this topic were reviewed and it was found that there are many (>150) different drivers acting for and against wastewater recycling. To deal with the challenge of comparing studies which entailed different research designs, a framework was developed which allowed the literature to be organized into comparable study contexts. Studies were categorized according to the level of analysis (wastewater recycling scheme, city, water utility, state, country, global) and outcome investigated (development/investment in new schemes, program implementation, percentage of wastewater recycled, percentage of water demand covered by recycled water, multiple outcomes). Findings across comparable case studies were then grouped according to the type (for or against recycling) and category of driver (social, natural, technical, economic, policy or business). The utility of the framework is demonstrated by summarizing the findings from four Australian studies at the city level. The framework offers a unique approach for disentangling the broad range of potential drivers for and against water recycling and to focus on those that seem relevant in specific study contexts. It may offer a valuable starting point for building hypotheses in future work. PMID- 26819380 TI - Integration of US/Fe(2+) and photo-Fenton in sequencing for degradation of landfill leachate. AB - The landfill leachate treated by sonication in presence of Fe(2+) (US/Fe(2+)) and then by photo-Fenton achieved the highest total organic carbon (TOC) removal efficiency among the screened processes. The lower initial pH, dosage of Fe(2+) and initial concentration of leachate were helpful in raising TOC removal efficiency of leachate by US/Fe(2+). The optimal conditions for the US-photo Fenton process were as follows: initial pH at 3.0, [H2O2]/[TOC0] at 2, [H2O2]/[Fe(2+)] at 5 and initial concentration of landfill leachate at 600 mg/L. The removal efficiency of TOC, chemical oxygen demand (COD) and 5-day biochemical oxygen demand (BOD5) were 68.3, 79.6 and 58.2%, while the BOD5/COD rose from 0.20 to 0.43 at optimum condition. Based on gas chromatography-mass spectrometry (GC MS) results, 36 of a total of 56 pollutants were completely degraded by US-photo Fenton treatment. PMID- 26819381 TI - Biodegradation of microcystin [Dha(7)]MC-LR by a novel microcystin-degrading bacterium in an internal airlift loop bioreactor. AB - Cyanobacterial hepatotoxin microcystins are a health problem found in bodies of water in Thailand. Bacteria capable of biodegrading microcystin [Dha(7)]MC-LR were isolated from the Bueng Nong Khot reservoir in Khon Kaen, Thailand. The bacterium Novosphingobium isolate KKU25s was shown to degrade [Dha(7)]MC-LR at a concentration of 25 MUg l(-1) at 30 degrees C within 24 h. Two intermediate by products (linearized peptide and tetrapeptide) and a cluster gene (mlrA, mlrB, mlrC and mlrD) that encodes four putative enzymes involved in [Dha(7)]MC-LR degradation were detected in KKU25s. KKU25s was also shown to form strong biofilms in microtiter plate assays. These assays were carried out in preparation for use of the bacterium in a bioreactor for [Dha(7)]MC-LR degradation. In an internal airlift loop bioreactor, the biodegradation of [Dha(7)]MC-LR by the bacterium was established in batch and continuous flow experiments. In the batch experiment, KKU25s degraded [Dha(7)]MC-LR at a concentration of 25 MUg l(-1) at 30 degrees C within 24 h, whereas in the continuous flow experiment, KKU25s degraded the toxin at the same concentration within 36 h. This study demonstrated that this bacterium could potentially be used to remove microcystins from water. PMID- 26819382 TI - Kinetic model of water disinfection using peracetic acid including synergistic effects. AB - The disinfection efficiencies of a commercial mixture of peracetic acid against Escherichia coli were studied in laboratory scale experiments. The joint and separate action of two disinfectant agents, hydrogen peroxide and peracetic acid, were evaluated in order to observe synergistic effects. A kinetic model for each component of the mixture and for the commercial mixture was proposed. Through simple mathematical equations, the model describes different stages of attack by disinfectants during the inactivation process. Based on the experiments and the kinetic parameters obtained, it could be established that the efficiency of hydrogen peroxide was much lower than that of peracetic acid alone. However, the contribution of hydrogen peroxide was very important in the commercial mixture. It should be noted that this improvement occurred only after peracetic acid had initiated the attack on the cell. This synergistic effect was successfully explained by the proposed scheme and was verified by experimental results. Besides providing a clearer mechanistic understanding of water disinfection, such models may improve our ability to design reactors. PMID- 26819383 TI - Prioritizing sewer rehabilitation projects using AHP-PROMETHEE II ranking method. AB - The aim of this paper is to develop a methodology for the prioritization of sewer rehabilitation projects for Algiers (Algeria) sewer networks to support the National Sanitation Office in its challenge to make decisions on prioritization of sewer rehabilitation projects. The methodology applies multiple-criteria decision making. The study includes 47 projects (collectors) and 12 criteria to evaluate them. These criteria represent the different issues considered in the prioritization of the projects, which are structural, hydraulic, environmental, financial, social and technical. The analytic hierarchy process (AHP) is used to determine weights of the criteria and the Preference Ranking Organization Method for Enrichment Evaluations (PROMETHEE II) method is used to obtain the final ranking of the projects. The model was verified using the sewer data of Algiers. The results have shown that the method can be used for prioritizing sewer rehabilitation projects. PMID- 26819384 TI - Investigation of furfural biodegradation in a continuous inflow cyclic biological reactor. AB - The performance of a continuous inflow cyclic biological reactor (CBR) containing moving media was investigated for the degradation of high concentrations of furfural. The effects of hydraulic retention time (HRT) and furfural initial concentrations (loading rate), as main operating parameters, on the bioreactor performance were studied. The results indicated that the CBR could remove over 98% of furfural and 71% of its chemical oxygen demand (COD) at inlet furfural concentrations up to 1,200 mg L(-1) (2.38 g L(-1) d(-1)), a 6-h cycle time and HRT of 12.1 h. The removal efficiency decreased slightly from 98 to 94% when HRT decreased from 12.1 to 10.5 h. The average removal efficiency of furfural and COD during the 345-day operational period under steady-state conditions were 97.7% and 82.1%, respectively. The efficiency also increased approximately 17.2% after addition of synthetic polyurethane cubes as moving media at a filling ratio of 10%. PMID- 26819385 TI - Mass balance and mass loading of polybrominated diphenyl ethers (PBDEs) in a tertiary wastewater treatment plant using SBSE-TD-GC/MS. AB - A mass loading and mass balance analysis was performed on selected polybromodiphenyl ethers (PBDEs) in the first full-scale indirect potable reuse treatment plant in the United States. Chemical analysis of PBDEs was performed using an environmentally friendly sample preparation technique, called stir-bar sorptive extraction (SBSE), coupled with thermal desorption and gas chromatography/mass spectrometry (GC/MS). The three most dominant PBDEs found in all the samples were: BDE-47, BDE-99 and BDE-100. In the wastewater influent, the concentrations of studied PBDEs ranged from 94 to 775 ng/L, and in the effluent, the levels were below the detection limit. Concentrations in sludge ranged from 50 to 182 ng/g. In general, a removal efficiency of 92-96% of the PBDEs in the plant was accomplished through primary and secondary processes. The tertiary treatment process was able to effectively reduce the aforementioned PBDEs to less than 10 ng/L (>96% removal efficiency) in the effluent. If PBDEs remain in the treated wastewater effluent, they may pose environmental and health impacts through aquifer recharge, irrigation, and sludge final disposal. PMID- 26819387 TI - Biotic and abiotic bisphenol-A removal from wastewater by activated sludge: effects of temperature, biomass, and bisphenol-A concentrations. AB - In this study, bisphenol-A (BPA) removal from synthetic wastewaters using a laboratory-scale activated sludge system was achieved. Activated (biotic) sludge was used for BPA elimination, whereas inactivated (abiotic) sludge was used during the adsorption study. In each step, six different BPA concentrations (5, 10, 20, 30, 40, and 50 mg L(-1)) were tested, and temperatures were set to 10, 20, and 30 degrees C in the shakers. Four different activated sludge concentrations (1,000, 2,000, 3,000, and 4,000 mg TSS L(-1)) were applied in the biotic study, and only 2,000 mg TSS L(-1) was used in the abiotic study. After settlement of the sludge in the shakers, supernatants and control groups were filtered and analyzed for BPA using high performance liquid chromatography. In the biotic study, BPA and chemical oxygen demand (COD) concentrations were reduced at 100% and 99% levels, respectively. However, the BPA concentrations during the abiotic study changed slightly at varying temperatures, whereas there was no change of BPA concentration observed in the control groups. Results indicate that the main factor of BPA removal in an activated sludge system is biological. Kinetic studies were also conducted. BPA removal was best fit to zero and first-order reaction kinetics, and the reaction rate constants are provided in this paper. PMID- 26819386 TI - Poultry slaughterhouse wastewater treatment plant for high quality effluent. AB - This paper assesses a wastewater treatment plant (WWTP) regarding the technology used, as well as organic matter and nutrient removal efficiencies aiming to optimize the treatment processes involved and wastewater reclamation. The WWTP consists of a dissolved air flotation (DAF) system, an upflow anaerobic sludge blanket (UASB) reactor, an aerated-facultative pond (AFP) and a chemical-DAF system. The removal efficiencies of chemical oxygen demand (COD) (97.9 +/- 1.0%), biochemical oxygen demand (BOD) (98.6 +/- 1.0%) and oil and grease (O&G) (91.1 +/ 5.2%) at the WWTP, the nitrogen concentration of 17 +/- 11 mg N-NH3 and phosphorus concentration of 1.34 +/- 0.93 mg PO4(-3)/L in the final effluent indicate that the processes used are suitable to comply with discharge standards in water bodies. Nitrification and denitrification tests conducted using biomass collected at three AFP points indicated that nitrification and denitrification could take place in the pond. PMID- 26819388 TI - Boron nitride nanoplates supported zero-valent iron nanocomposites for enhanced decolorization of methyl orange with the assistance of ultrasonic irradiation. AB - In this work, boron nitride nanoplates (BNNPs) supported nanoscale zero-valent iron (nZVI) was prepared through facile liquid-phase chemical reduction of ferric ion by borohydride under ambient conditions in the presence of BNNPs. The nZVI@BNNPs hybrids were characterized by scanning electron microscopy, X-ray diffraction and magnetic properties measurement. The hybrid material was evaluated for decolorization of a common azo dye, methyl orange (MO), with the assistance of ultrasonic irradiation. Results exhibited that a complete decolorization of 100 mg/L MO was achieved within 6 min using nZVI@BNNPs as the active material. Compared with bare nZVI and BNNPs, nZVI@BNNPs provided a faster reaction process for MO decolorization. The kinetic rate constants of MO decolorization reached 0.8175 min(-1) under ultrasound-assisted condition due to the synergistic effect of ultrasonic irradiation. Fluorescence spectrum experiment confirmed that hydroxyl radicals could be generated in the system combined nZVI with ultrasonic irradiation, and as a result, hydroxyl radicals would contribute to the decolorization process of MO. PMID- 26819389 TI - Impact of fine mesh sieve primary treatment on nitrogen removal in moving bed biofilm reactors. AB - The purpose of this project was to investigate the effect of selective particle removal during primary treatment on nitrogen removal in moving bed biofilm reactors (MBBRs). Two small MBBR pilot plants were operated in parallel, where one train treated 2 mm screened municipal wastewater and the other train treated wastewater that had passed through a Salsnes Filter SF1000 rotating belt sieve (RBS) with a 33 us sieve cloth. The SF1000 was operated without a filter mat on the belt. The tests confirmed that, for the wastewater characteristics at the test plant, Salsnes Filter primary treatment with a 33 us RBS and no filter mat produced a primary effluent that was close to optimum. Removal of organic matter with the 33 us sieve had no negative effect on the denitrification process. Nitrification rates improved by 10-15% in the train with 33 us RBS primary treatment. Mass balance calculations showed that without RBS primary treatment, the oxygen demand in the biological system was 36% higher. Other studies have shown that the sludge produced by RBS primary treatment is beneficial for biogas production and will also significantly improve sludge dewatering of the combined primary and biological sludge. PMID- 26819390 TI - Relationships between sources of acid mine drainage and the hydrochemistry of acid effluents during rainy season in the Iberian Pyrite Belt. AB - In the Iberian Pyrite Belt (IPB), southwest Spain, a prolonged and intense mining activity of more than 4,500 years has resulted in almost a hundred mines scattered through the region. After years of inactivity, these mines are still causing high levels of hydrochemical degradation in the fluvial network. This situation represents a unique scenario in the world, taking into consideration its magnitude and intensity of the contamination processes. In order to obtain a benchmark regarding the degree of acid mine drainage (AMD) pollution in the aquatic environment, the relationship between the areas occupied by the sulfide mines and the characteristics of the respective effluents after rainfall was analysed. The methodology developed, which includes the design of a sampling network, analytical treatment and cluster analysis, is a useful tool for diagnosing the contamination level by AMD in an entire metallogenic province, at the scale of each mining group. The results presented the relationship between sulfate, total dissolved solids and electrical conductivity, as well as other parameters that are typically associated with AMD and the major elements that compose the polymetallic sulfides of IPB. This analysis also indicates the low level of proximity between the affectation area and the other variables. PMID- 26819391 TI - Recovering biomethane and nutrients from anaerobic digestion of water hyacinth (Eichhornia crassipes) and its co-digestion with fruit and vegetable waste. AB - The potential to recover bioenergy from anaerobic digestion of water hyacinth (WH) and from its co-digestion with fruit and vegetable waste (FVW) was investigated. Initially, biogas and methane production were studied using the biochemical methane potential (BMP) test at 2 g volatile solids (VS) L(-1) of substrate concentration, both in the digestion of WH alone and in its co digestion with FVW (WH-FVW ratio of 70:30). Subsequently, the biogas production was optimized in terms of total solids (TS) concentration, testing 4 and 6% of TS. The BMP test showed a biogas yield of 0.114 m(3) biogas kg(-1) VSadded for WH alone. On the other hand, the biogas potential from the WH-FVW co-digestion was 0.141 m(3) biogas kg(-1) VSadded, showing an increase of 23% compared to that of WH alone. Maximum biogas production of 0.230 m(3) biogas kg(-1) VSadded was obtained at 4% of TS in the co-digestion of WH-FVW. Using semi-continuously stirred tank reactors, 1.3 m(3) biogas yield kg(-1) VSadded was produced using an organic loading rate of 2 kg VS m(-3) d(-1) and hydraulic retention time of 15 days. It was also found that a WH-FVW ratio of 80:20 improved the process in terms of pH stability. Additionally, it was found that nitrogen can be recovered in the liquid effluent with a potential for use as a liquid fertilizer. PMID- 26819392 TI - Impacts of urbanization on the prevalence of antibiotic-resistant Escherichia coli in the Chaophraya River and its tributaries. AB - River water samples were taken from 32 locations around the basin of Chaophraya River and its four major tributaries in Thailand to investigate resistance ratios of Escherichia coli isolates to eight antibiotic agents of amoxicillin, sulfamethoxazole/trimethoprim, tetracycline, doxytetracycline, ciprofloxacin, levofloxacin, norfloxacin and ofloxacin. Principal component analysis was performed to characterize resistance patterns of the samples. Relevancy of the obtained principal components with urban land use and fecal contamination of the river were examined. The ratio of antibiotic-resistant bacteria is likely to increase when urban land use near the sampling site exceeds a certain ratio. The resistance ratio to fluoroquinolones tends to be high in a highly populated area. Meanwhile, no significant contribution of fecal contamination was found to increase the resistance ratio. These results suggest that an antibiotic resistance ratio is dependent on conditions of local urbanization rather than the upstream conditions, and that the major sources of antibiotic-resistant bacteria in the Chaophraya River basin are possibly point sources located in the urban area which contains a high ratio of resistant bacteria. PMID- 26819393 TI - Chemical pretreatment of combined sewer overflows for improved UV disinfection. AB - The aim of this research was to better understand chemical pre-treatment of combined sewer overflows (CSOs) for subsequent ultraviolet (UV) disinfection. Approximately 200 jar tests were completed. Alum (Al2(S04)3.12H2O) resulted in a higher UV light transmission (UVT), and equivalent total suspended solids (TSS) removal, than ferric chloride (FeCl3). An alum dose of 20 mg/L increased the UVT of the raw CSO from 30 to 60% after settling. The addition of 100 mg/L of alum maximized UVT reaching approximately 85%. Flocculation did not increase UVT. However, it did improve the removal of TSS. Cationic polymers worked quickly compared with metal coagulants, but only reached a UVT of 60%. A high positive charge density on the polymer improved the removal of turbidity when compared with low charge, but did not affect UVT. If the goal is to maximise UVT, a very high alum dose may be preferred. If the goal is to minimize coagulant dose with moderate UV performance, cationic polymer at approximately 3 mg/L is recommended. PMID- 26819394 TI - Effects of metal ions on biomass and 5-aminolevulinic acid production in Rhodopseudomonas palustris wastewater treatment. AB - This work investigated the effects of eight metal ions on Rhodopseudomonas palustris growth and 5-aminolevulinic acid (ALA) yield in wastewater treatment. Results show that metal ions (Mg(2+) of 15 mmol/L, Fe(2+) of 400 MUmol/L, Co(2+) of 4 MUmol/L, Ni(2+) of 8 MUmol/L and Zn(2+) of 4 MUmol/L) could effectively improve the chemical oxygen demand (COD) removal, Rp. palustris biomass and ALA yield. The highest ALA yield of 13.1 mg/g-biomass was achieved with Fe(2+) of 400 MUmol/L. ALA yields were differentially increased under different metal ions in the following order: Fe(2+) group > Mg(2+) group > Co(2+) group = Ni(2+) group > Zn(2+) group = Mo(2+) group > control. Cu(2+) and Mn(2+) inhibited Rp. palustris growth and ALA production. Mechanism analysis revealed that metal ions changed ALA yields by influencing the activities of ALA synthetase and ALA dehydratase. PMID- 26819395 TI - Ibuprofen removal from aqueous solution by in situ electrochemically generated ferrate(VI): proof-of-principle. AB - The possibility of removing pharmaceuticals from aqueous solutions was examined using ibuprofen (Ibu) oxidation as an example, using in situ electrochemically synthesized ferrate(VI), a strong oxidant and coagulant, with forming of non harmful byproducts. A solution of ibuprofen of 206 mg/L in 0.1 M phosphate buffer solution was treated with different amounts of fresh, electrochemically synthesized ferrate(VI). The changes of ibuprofen concentration in samples were determined using a UV-Vis spectrophotometer. The extent of mineralization was estimated using the changes in chemical oxygen demand (COD) values and total organic carbon (TOC) values of test samples. The largest reduction of the concentration of Ibu (41.75%) was obtained by adding 69.2 mg/L ferrate(VI) as Fe (Ibu: Fe = 1: 0.34). An effective removal of ibuprofen from aqueous solutions was recorded up to 68% and it can be done by using ferrate(VI) in the ratio Ibu: Fe = 1:3 as Fe. The possibility of ibuprofen removal by ferrate(VI) was confirmed by COD and TOC results, which demonstrated reduction up to 65% and 63.6%, respectively. PMID- 26819396 TI - Recycling agriculture wastes of ramie stalk as bioadsorbents for Cd(2+) removal: a kinetic and thermodynamic study. AB - In this study, we exhibit the recycling of agriculture wastes of ramie stalk as bioadsorbents for Cd(2+) removal. Based on our experimental results, it is realized that Cd(2+) adsorption to ramie stalk is highly pH sensitive, indicating the adsorption is driven by surface complexation reaction. The high adsorption capacity of ramie stalk toward Cd(2+) (qm = 10.33 mg g(-1), 0.09 mol-Cd g(-1)), which corresponds to around 21.95% of active adsorption sites available of ramie stalk, is believed to be closely related to its high cellulose and lignin content. The inhomogeneous surface of ramie stalk due to the high cellulose and lignin content also accounts for the observation that the adsorption kinetic is described well by the pseudo second order kinetic model. Results from thermodynamic studies suggest that the adsorption process is endothermic and spontaneous. All these properties demonstrate the potential of ramie stalk as a low cost bioadsorbent for the application of heavy metal removal. PMID- 26819397 TI - Tropical stormwater nutrient degradation using nano-TiO2 in photocatalytic reactor detention pond. AB - The photo-degradation of nutrients in stormwater in photocatalytic reactor wet detention pond using nano titanium dioxide (TiO2) in concrete was investigated in a scale model as a new stormwater treatment method. Degradation of phosphate and nitrate in the presence of nano-TiO2 under natural ultra violet (UV) from tropical sunlight was monitored for 3 weeks compared with normal ponds. Two types of cement, including ordinary Portland and white cement mixed with TiO2 nano powder, were used as a thin cover to surround the body of the pond. Experiments with and without the catalyst were carried out for comparison and control. Average Anatase diameter of 25 nm and Rutile 100 nm nano particles were applied at three different mixtures of 3, 10 and 30% weight. The amounts of algae available orthophosphate and nitrate, which cause eutrophication in the ponds, were measured during the tests. Results revealed that the utilization of 3% up to 30% weight nano-TiO2 can improve stormwater outflow quality by up to 25% after 48 h and 57% after 3 weeks compared with the control sample in normal conditions with average nutrient (phosphate and nitrate) removal of 4% after 48 h and 10% after 3 weeks. PMID- 26819398 TI - Control of Microthrix parvicella by aluminium salts addition. AB - Aluminium and iron chloride were added to a biological nutrient removal pilot plant (1,500 population equivalent) treating urban wastewater to investigate the control of Microthrix parvicella bulking and foaming by metallic salts. Monitoring plant performance over two 6-month periods showed a slight impact on the removal efficiencies. Addition of metallic salts (Me; aluminium or aluminium + iron) at a concentration of 41 mmol Me(kg MLSS.d) (MLSS: mixed liquor suspended solids) over 70 days allowed a stabilization of the diluted sludge volume index (DSVI), whereas higher dosages (94 mmol Me(kg MLSS.d) over 35 days or 137 mmol Me(kg MLSS.d) over 14 days induced a significant improvement of the settling conditions. Microscopic observations showed a compaction of biological aggregates with an embedding of filamentous bacteria into the flocs that is not specific to M. parvicella as bacteria from phylum Chloroflexi are embedded too. The quantitative polymerase chain reaction targeting M. parvicella further indicated a possible growth limitation in addition to the flocculation impact at the high dosages of metallic salts investigated. DSVI appeared to be correlated with the relative abundance of M. parvicella. PMID- 26819399 TI - Comparative studies on adsorptive removal of heavy metal ions by biosorbent, bio char and activated carbon obtained from low cost agro-residue. AB - In this study, Fe(III) and Cr(III) metal ion adsorption processes were carried out with three adsorbents in batch experiments and their adsorption performance was compared. These adsorbents were sesame stalk without pretreatment, bio-char derived from thermal decomposition of biomass, and activated carbon which was obtained from chemical activation of biomass. Scanning electron microscopy and Fourier transform-infrared techniques were used for characterization of adsorbents. The optimum conditions for the adsorption process were obtained by observing the influences of solution pH, adsorbent dosage, initial solution concentration, contact time and temperature. The optimum adsorption efficiencies were determined at pH 2.8 and pH 4.0 for Fe(III) and Cr(III) metal ion solutions, respectively. The experimental data were modelled by different isotherm models and the equilibriums were well described by the Langmuir adsorption isotherm model. The pseudo-first-order, pseudo-second-order kinetic, intra-particle diffusion and Elovich models were applied to analyze the kinetic data and to evaluate rate constants. The pseudo-second-order kinetic model gave a better fit than the others. The thermodynamic parameters, such as Gibbs free energy change DeltaG degrees , standard enthalpy change DeltaH degrees and standard entropy change DeltaS degrees were evaluated. The thermodynamic study showed the adsorption was a spontaneous endothermic process. PMID- 26819400 TI - Measuring total mercury due to small-scale gold mining activities to determine community vulnerability in Cihonje, Central Java, Indonesia. AB - This research is comparative study of gold mining and non-gold mining areas, using four community vulnerability indicators. Vulnerability indicators are exposure degree, contamination rate, chronic, and acute toxicity. Each indicator used different samples, such as wastewater from gold mining process, river water from Tajum river, human hair samples, and health questionnaire. This research used cold vapor atomic absorption spectrometry to determine total mercury concentration. The result showed that concentration of total mercury was 2,420 times than the maximum content of mercury permitted in wastewater based on the Indonesian regulation. Moreover, the mercury concentration in river water reached 685 ng/l, exceeding the quality threshold standards of the World Health Organization (WHO). The mercury concentration in hair samples obtained from the people living in the research location was considered to identify the health quality level of the people or as a chronic toxicity indicator. The highest mercury concentration--i.e. 17 ng/mg, was found in the gold mining respondents. Therefore, based on the total mercury concentration in the four indicators, the community in the gold mining area were more vulnerable to mercury than communities in non-gold mining areas. It was concluded that the community in gold mining area was more vulnerable to mercury contamination than the community in non-gold mining area. PMID- 26819401 TI - Tylosin effect on methanogenesis in an anaerobic biomass from swine wastewater treatment. AB - The effect of different concentrations of tylosin on methane production was investigated: first methanogenesis in a biomass without contact with the antibiotic, and later the ability of the sludge to adapt to increasing concentrations of tylosin. Results showed that, for biomass that had no contact with the antibiotic, the presence of tylosin inhibits the generation of methane even at concentrations as small as 0.01 mg L(-1), and samples at concentrations above 0.5 mg L(-1) produced practically no methane, whereas, in the digesters acclimated in the presence of tylosin at a concentration of 0.01 to 0.065 mg L( 1), methanogenesis is not inhibited in the presence of antibiotic and the generation of methane is improved. This behaviour suggests the microorganisms have developed not only resistance to the antibiotic but also an ability to metabolize it. PMID- 26819402 TI - Helping professionals and Border Force secrecy: effective asylum-seeker healthcare requires independence from callous policies. AB - OBJECTIVE: To examine the Australian Border Force Act (BFA) and its context, its implications for asylum-seeker healthcare and professionals, and contemporary and historical parallels. CONCLUSIONS: Prolonged immigration detention and policies aiming to deter irregular migration cause maritime asylum-seekers undeniable, well-publicised harms and (notwithstanding claims about preventing drownings) show reckless indifference and calculated cruelty. Service personnel may be harmed. Such policies misuse helping professionals to underwrite state abuses and promote public numbing and indifference, resembling other state abuses in the 'war on terror' and (with qualification) historical counterparts, e.g. Nazi Germany. Human service practitioners and organisations recently denounced the BFA that forbids disclosure about these matters.Continuing asylum-seeker healthcare balances the likelihood of effective care and monitoring with lending credibility to abuses. Boycotting it might sacrifice scrutiny and care, fail to compel professionals and affect temporary overseas workers. Entirely transferring healthcare from immigration to Federal and/or State health departments, with resources augmented to adequate standard, would strengthen clinical independence and quality, minimise healthcare's being securitised and politicised, and uphold ethical codes. Such measures will not resolve detention's problems, but coupled with independent auditing, would expose and moderate detention's worst effects, promoting changes in national conversation and policy-making. PMID- 26819403 TI - A critical interpretive synthesis of the most commonly used self-report measures in Australian mental health research. AB - OBJECTIVE: To critically examine the self-report measures most commonly used in Australian mental health research in the last 10 years. METHOD: A critical interpretive synthesis was conducted using seven outcome measures that were identified as most popular in 43 studies from three mental health journals. RESULTS: Results suggest that the amount and type of language used in outcome measures is important in both increasing the accuracy of the data collected and fostering positive experiences of data collection for participants. CONCLUSIONS: Results indicate that many of the measures most often used in Australian mental health research may not align with the current contemporary philosophy of mental health clinical practice in Australia. PMID- 26819404 TI - First episode mania following cessation of varenicline (Champix). AB - OBJECTIVES: To describe a case of first episode mania and in which varenicline (Champix) or its withdrawal appears to have been the precipitating factor. METHODS: The clinical presentation and progress are detailed and the relevant literature in relation to varenicline is provided. RESULTS: The case report adds to the literature indicating that varenicline may induce a range of mood states, albeit with reported incidents of mania being rare. CONCLUSIONS: In reviewing causes of mood states, including mania, seeking information on any exposure to varenicline would appear to be relevant. PMID- 26819405 TI - Antipsychotic prescribing and its correlates in New Zealand. AB - OBJECTIVES: Antipsychotics are the cornerstone of schizophrenia management. There is substantial literature on their efficacy and optimal use. Doubts remain, however, regarding the translation of this knowledge into day-to-day practice. This study aimed to investigate antipsychotic prescribing in three New Zealand regions and its relationship to clinical guidelines and patient characteristics. METHODS: We studied 451 patients discharged from inpatient units with a diagnosis of schizophrenia or a related disorder (International Classification of Disease, version 10) between July 2009 and December 2011. Available information included patient demography, legal status, prescribed medications, duration of index admission and prescriber's country of postgraduate training and years of postgraduate experience. RESULTS: There was a high rate (33.7%) of multiple antipsychotic prescription, and lower than expected clozapine use (20%); Maori were prescribed clozapine more frequently than non-Maori (24% vs. 13%, respectively). Compulsory treatment was associated with more use of injectable medication and increased length of stay in hospital. Clinician characteristics did not significantly influence prescribing. CONCLUSIONS: Observed prescribing practice aligned with existing guidelines except for antipsychotic polypharmacy and clozapine under-utilisation. PMID- 26819407 TI - ZeitZeiger: supervised learning for high-dimensional data from an oscillatory system. AB - Numerous biological systems oscillate over time or space. Despite these oscillators' importance, data from an oscillatory system is problematic for existing methods of regularized supervised learning. We present ZeitZeiger, a method to predict a periodic variable (e.g. time of day) from a high-dimensional observation. ZeitZeiger learns a sparse representation of the variation associated with the periodic variable in the training observations, then uses maximum-likelihood to make a prediction for a test observation. We applied ZeitZeiger to a comprehensive dataset of genome-wide gene expression from the mammalian circadian oscillator. Using the expression of 13 genes, ZeitZeiger predicted circadian time (internal time of day) in each of 12 mouse organs to within ~1 h, resulting in a multi-organ predictor of circadian time. Compared to the state-of-the-art approach, ZeitZeiger was faster, more accurate and used fewer genes. We then validated the multi-organ predictor on 20 additional datasets comprising nearly 800 samples. Our results suggest that ZeitZeiger not only makes accurate predictions, but also gives insight into the behavior and structure of the oscillator from which the data originated. As our ability to collect high-dimensional data from various biological oscillators increases, ZeitZeiger should enhance efforts to convert these data to knowledge. PMID- 26819406 TI - Efficient enzymatic synthesis and dual-colour fluorescent labelling of DNA probes using long chain azido-dUTP and BCN dyes. AB - A sterically undemanding azide analogue of dTTP (AHP dUTP) with an alkyl chain and ethynyl attachment to the nucleobase was designed and incorporated into DNA by primer extension, reverse transcription and polymerase chain reaction (PCR). An azide-modified 523 bp PCR amplicon with all 335 thymidines replaced by AHP dU was shown to be a perfect copy of the template from which it was amplified. Replacement of thymidine with AHP dU increases duplex stability, accounting in part for the high incorporation efficiency of the azide-modified triphosphate. Single-stranded azide-labelled DNA was conveniently prepared from PCR products by lambda-exonuclease digestion and streptavidin magnetic bead isolation. Efficient fluorescent labelling of single and double-stranded DNA was carried out using dyes functionalized with bicyclo[6.1.0]non-4-yne (BCN) via the strain-promoted alkyne-azide cycloaddition (SPAAC) reaction. This revealed that the degree of labelling must be carefully controlled to achieve optimum fluorescence and avoid fluorescence quenching. Dual-coloured probes were obtained in a single tube fluorescent labelling reaction; and varying the ratios of the two dyes provides a simple method to prepare DNA probes with unique fluorescent signatures. AHP dUTP is a versatile clickable nucleotide with potentially wide applications in biology and nanotechnology including single molecule studies and synthesis of modified aptamer libraries via SELEX. PMID- 26819408 TI - ALVIS: interactive non-aggregative visualization and explorative analysis of multiple sequence alignments. AB - Sequence Logos and its variants are the most commonly used method for visualization of multiple sequence alignments (MSAs) and sequence motifs. They provide consensus-based summaries of the sequences in the alignment. Consequently, individual sequences cannot be identified in the visualization and covariant sites are not easily discernible. We recently proposed Sequence Bundles, a motif visualization technique that maintains a one-to-one relationship between sequences and their graphical representation and visualizes covariant sites. We here present Alvis, an open-source platform for the joint explorative analysis of MSAs and phylogenetic trees, employing Sequence Bundles as its main visualization method. Alvis combines the power of the visualization method with an interactive toolkit allowing detection of covariant sites, annotation of trees with synapomorphies and homoplasies, and motif detection. It also offers numerical analysis functionality, such as dimension reduction and classification. Alvis is user-friendly, highly customizable and can export results in publication quality figures. It is available as a full-featured standalone version (http://www.bitbucket.org/rfs/alvis) and its Sequence Bundles visualization module is further available as a web application (http://science practice.com/projects/sequence-bundles). PMID- 26819410 TI - DeltaNp63 activates the Fanconi anemia DNA repair pathway and limits the efficacy of cisplatin treatment in squamous cell carcinoma. AB - TP63, a member of the p53 gene family gene, encodes the DeltaNp63 protein and is one of the most frequently amplified genes in squamous cell carcinomas (SCC) of the head and neck (HNSCC) and lungs (LUSC). Using an epiallelic series of siRNAs with intrinsically different knockdown abilities, we show that the complete loss of DeltaNp63 strongly impaired cell proliferation, whereas partial DeltaNp63 depletion rendered cells hypersensitive to cisplatin accompanied by an accumulation of DNA damage. Expression profiling revealed wide-spread transcriptional regulation of DNA repair genes and in particular Fanconi anemia (FA) pathway components such as FANCD2 and RAD18 - known to be crucial for the repair of cisplatin-induced interstrand crosslinks. In SCC patients DeltaNp63 levels significantly correlate with FANCD2 and RAD18 expression confirming DeltaNp63 as a key activator of the FA pathway in vivo Mechanistically, DeltaNp63 bound an upstream enhancer of FANCD2 inactive in primary keratinocytes but aberrantly activated by DeltaNp63 in SCC. Consistently, depletion of FANCD2 sensitized to cisplatin similar to depletion of DeltaNp63. Together, our results demonstrate that DeltaNp63 directly activates the FA pathway in SCC and limits the efficacy of cisplatin treatment. Targeting DeltaNp63 therefore would not only inhibit SCC proliferation but also sensitize tumors to chemotherapy. PMID- 26819409 TI - The Kub5-Hera/RPRD1B interactome: a novel role in preserving genetic stability by regulating DNA mismatch repair. AB - Ku70-binding protein 5 (Kub5)-Hera (K-H)/RPRD1B maintains genetic integrity by concomitantly minimizing persistent R-loops and promoting repair of DNA double strand breaks (DSBs). We used tandem affinity purification-mass spectrometry, co immunoprecipitation and gel-filtration chromatography to define higher-order protein complexes containing K-H scaffolding protein to gain insight into its cellular functions. We confirmed known protein partners (Ku70, RNA Pol II, p15RS) and discovered several novel associated proteins that function in RNA metabolism (Topoisomerase 1 and RNA helicases), DNA repair/replication processes (PARP1, MSH2, Ku, DNA-PKcs, MCM proteins, PCNA and DNA Pol delta) and in protein metabolic processes, including translation. Notably, this approach directed us to investigate an unpredicted involvement of K-H in DNA mismatch repair (MMR) where K-H depletion led to concomitant MMR deficiency and compromised global microsatellite stability. Mechanistically, MMR deficiency in K-H-depleted cells was a consequence of reduced stability of the core MMR proteins (MLH1 and PMS2) caused by elevated basal caspase-dependent proteolysis. Pan-caspase inhibitor treatment restored MMR protein loss. These findings represent a novel mechanism to acquire MMR deficiency/microsatellite alterations. A significant proportion of colon, endometrial and ovarian cancers exhibit k-h expression/copy number loss and may have severe mutator phenotypes with enhanced malignancies that are currently overlooked based on sporadic MSI+ screening. PMID- 26819411 TI - Novel RNA-binding activity of MYF5 enhances Ccnd1/Cyclin D1 mRNA translation during myogenesis. AB - Skeletal muscle contains long multinucleated and contractile structures known as muscle fibers, which arise from the fusion of myoblasts into multinucleated myotubes during myogenesis. The myogenic regulatory factor (MRF) MYF5 is the earliest to be expressed during myogenesis and functions as a transcription factor in muscle progenitor cells (satellite cells) and myocytes. In mouse C2C12 myocytes, MYF5 is implicated in the initial steps of myoblast differentiation into myotubes. Here, using ribonucleoprotein immunoprecipitation (RIP) analysis, we discovered a novel function for MYF5 as an RNA-binding protein which associated with a subset of myoblast mRNAs. One prominent MYF5 target was Ccnd1 mRNA, which encodes the key cell cycle regulator CCND1 (Cyclin D1). Biotin-RNA pulldown, UV-crosslinking and gel shift experiments indicated that MYF5 was capable of binding the 3' untranslated region (UTR) and the coding region (CR) of Ccnd1 mRNA. Silencing MYF5 expression in proliferating myoblasts revealed that MYF5 promoted CCND1 translation and modestly increased transcription of Ccnd1 mRNA. Accordingly, overexpressing MYF5 in C2C12 cells upregulated CCND1 expression while silencing MYF5 reduced myoblast proliferation as well as differentiation of myoblasts into myotubes. Moreover, MYF5 silencing reduced myogenesis, while ectopically restoring CCND1 abundance partially rescued the decrease in myogenesis seen after MYF5 silencing. We propose that MYF5 enhances early myogenesis in part by coordinately elevating Ccnd1 transcription and Ccnd1 mRNA translation. PMID- 26819412 TI - High-resolution analysis of the human retina miRNome reveals isomiR variations and novel microRNAs. AB - MicroRNAs play a fundamental role in retinal development and function. To characterise the miRNome of the human retina, we carried out deep sequencing analysis on sixteen individuals. We established the catalogue of retina-expressed miRNAs, determined their relative abundance and found that a small number of miRNAs accounts for almost 90% of the retina miRNome. We discovered more than 3000 miRNA variants (isomiRs), encompassing a wide range of sequence variations, which include seed modifications that are predicted to have an impact on miRNA action. We demonstrated that a seed-modifying isomiR of the retina-enriched miR 124-3p was endowed with different targeting properties with respect to the corresponding canonical form. Moreover, we identified 51 putative novel, retina specific miRNAs and experimentally validated the expression for nine of them. Finally, a parallel analysis of the human Retinal Pigment Epithelium (RPE)/choroid, two tissues that are known to be crucial for retina homeostasis, yielded notably distinct miRNA enrichment patterns compared to the retina. The generated data are accessible through an ad hoc database. This study is the first to reveal the complexity of the human retina miRNome at nucleotide resolution and constitutes a unique resource to assess the contribution of miRNAs to the pathophysiology of the human retina. PMID- 26819418 TI - [Mediated mechanism of NDRG2 in the regulation of neutrophil nuclear transcription factor-kappaB signaling pathway through the deubiquitylating enzyme of Zc3h12d]. AB - OBJECTIVE: To explore the role NDRG2/Zc3h12d in the regulation of neutrophil nuclear transcription factor-kappaB signaling pathway and the underlying mechanisms.? METHODS: Sixteen HBE cells were incubated with lipopolysaccharide (LPS) to establish airway mucus hypersecretion model, which was transfected with NDRG2 or Zc3h12d siRNA. The cells were divided into 5 groups: a LPS+NDRG2 siRNA (Group A), a LPS+ NDRG2 and Zc3h12d siRNAs (Group B), a LPS+Zc3h12d siRNA (Group C), a LPS+ empty plasmid (Group D), and a negative control group (Group E). The reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression level of mucin (MUC) 5AC mRNA. The levels of MUC5AC and the inflammatory factors were examined by the enzyme-linked immunosorbent assay (ELISA). The NF-kappaB p65 and the Zc3h12d protein levels were measured by Western blot. The MUC5C expression was further examined by laser confocal method.? RESULTS: Compared with Group B, the levels of MUC5AC mRNA and protein in Group A were decreased (P<0.05), there was no significant difference in the MUC5AC mRNA and MUC5AC protein levels between the Group B and the Group C (P>0.05). Compared with Group D, the MUC5AC (mRNA and protein) and inflammatory factor levels in the Group A were significantly decreased (P<0.05); compared with Group E, after incubation with LPS, the levels of MUC5AC (mRNA and protein) and inflammatory factors in the Group D was increased, with significantly difference (P<0.05).? CONCLUSION: NDRG2 can regulate the function of NF-kappaB signaling pathway through the deubiquitylating enzyme of Zc3h12d. PMID- 26819413 TI - LncRNA OIP5-AS1/cyrano sponges RNA-binding protein HuR. AB - The function of the vast majority of mammalian long noncoding (lnc) RNAs remains unknown. Here, analysis of a highly abundant mammalian lncRNA, OIP5-AS1, known as cyrano in zebrafish, revealed that OIP5-AS1 reduces cell proliferation. In human cervical carcinoma HeLa cells, the RNA-binding protein HuR, which enhances cell proliferation, associated with OIP5-AS1 and stabilized it. Tagging OIP5-AS1 with MS2 hairpins to identify associated microRNAs revealed that miR-424 interacted with OIP5-AS1 and competed with HuR for binding to OIP5-AS1. We further identified a 'sponge' function for OIP5-AS1, as high levels of OIP5-AS1 increased HuR-OIP5-AS1 complexes and prevented HuR interaction with target mRNAs, including those that encoded proliferative proteins, while conversely, lowering OIP5-AS1 increased the abundance of HuR complexes with target mRNAs. We propose that OIP5 AS1 serves as a sponge or a competing endogenous (ce)RNA for HuR, restricting its availability to HuR target mRNAs and thereby repressing HuR-elicited proliferative phenotypes. PMID- 26819419 TI - [Autophagy inhibitor 3-methyladenine enhances the sensitivity of nasopharyngeal carcinoma cells to chemotherapy and radiotherapy]. AB - OBJECTIVE: To explore the effects of 3-methyladenine (3-MA, an autophagy inhibitor) on sensitivities of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy and the underlying mechanisms.? METHODS: Cell proliferation was examined by MTT and colony formation assay, while cell apoptosis was evaluated by annexin V/PI double staining and 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) staining. Mitochondrial membrane potential was measured by commercial kit (JC-1). The expression of endoplasmic reticulum stress (ERS) related protein, glucose-regulated protein 78 (GRP78) and autophagy-related protein beclin1, microtubule-associated protein 1 light chain 3 (LC3) were examined by Western blot.? RESULTS: Cisplatin (DDP), ionizing radiation (IR) or tunicamycin (TM) treatment obviously inhibited the proliferation of HONE-1 cells in a concentration-dependent and time-dependent manner. Compared with control group, pretreatment with 1 mmol/L of 3-MA significantly ?reduced cell viability and enhanced the apoptosis in the DDP (6.00 MUmol/L), 4.00 Gy IR or TM (1.00 MUmol/L) groups. There was no significant difference in the apoptosis between the DDP (5.8%) and 4Gy IR (6.7%) groups. Compared with the control group, protein levels of GRP78, beclin1 and lipid-conjugated membrane-bound form (LC3-II) were significantly increased after the treatment of DDP, 4.00 Gy IR or TM, which were inhibited by pretreatment of 3-MA.? CONCLUSION: 3-MA can sensitize HONE-1 cells to chemotherapy and radiotherapy, which is related to prevention of endoplasmic reticulum stress-induced autophagy in nasopharyngeal carcinoma cells. PMID- 26819420 TI - [MiR-519 inhibits gastric cancer cell activity through regulation of HuR expression]. AB - OBJECTIVE: To investigate the role of miR-519 in regulating the cell activity of gastric cancer. ? METHODS: The expression of miR-519 was measured by qPCR. The protein expression of HuR was detected by Western blot. MTT assay was used to detect the cell activity of gastric cancer cells.? RESULTS: The protein level of HuR in the gastric cancer cells was higher than that in the control cells. Over expression of HuR resulted in the increase in the cell activity of gastric cancer (P<0.001). Suppression of HuR decreased the cell activity of gastric cancer (P=0.001). The miR-519 level in the gastric cancer cells was lower than that in the control cells (P=0.001). Over-expression of miR-519 decreased the protein level of HuR and the activity of gastric cancer cells.? CONCLUSION: MiR-may inhibit the gastric cancer cell activity through suppression of HuR expression. PMID- 26819421 TI - [Value of detection of preoperative urinary soluble Fas expression in predicting the recurrence of non-muscle invasive bladder cancer]. AB - OBJECTIVE: To investigate the clinical value of detection of preoperative urinary soluble Fas (sFas) expression in predicting the recurrence of non-muscle invasive bladder cancer (NMIBC).? METHODS: We performed a prospective research, which included 128 cases with NMIBC from January 2008 to April 2011. Expression levels of sFas in urine, which was saved at the first morning from preoperative NMIBC patients, were analyzed by ELISA. Clinical and pathological data, European Organization for Research and Treatment of Cancer (EORTC) risk group category, follow-up data and urinary sFas values were collected from each patient, and each prognostic outcome was evaluated by statistical analysis of non-parametric test. Urinary sFas values and recurrence-free probabilities were estimated by the Kaplan-Meier method and compared by the log rank test. Cox proportional hazards regression models were performed to determine the independent predictors of NMIBC recurrence. The prognosis index (PI) was established.? RESULTS: The urinary sFas level was significantly elevated in the NMIBC cases with a higher stage or grade or high-risk EORTC group category than in those with a lower stage or grade or low-risk EORTC group category (each P<0.05), regardless of age or gender (P>0.05). Kaplan-Meier analysis revealed a significant increase in incidence of recurrence in the NMIBC patients with high sFas levels in the urine (P<0.001). According to Cox regression analysis, the urinary sFas level and EORTC risk group category (each P<0.05) were the independent predictors of NMIBC recurrence. Based on the outcome of Cox regression, the formula of PI=(0.004*sFas value+1.179*EORTC score) was established.? CONCLUSION: Our study indicates that urinary sFas test may help to identify NMIBC patients at risk of tumor recurrence and it deserves further research. PMID- 26819422 TI - [Value of endobronchial ultrasound elastography in the diagnosis of mediastinal and hilar lymph node metastasis in lung cancer]. AB - OBJECTIVE: To assess the value of endobronchial ultrasound elastography in the diagnosis of mediastinal and hilar lymph node metastasis in lung cancer. ? METHODS: A total of 40 patients with lung cancer underwent ultrasonic bronchoscope examination before operation. Elastography and standard endobronchial ultrasound (EBUS) of lymph nodes were performed before EBUS-guided transbronchial needle aspiration (EBUS-TBNA). The elastography characteristics was compared between benign and malignant lymph nodes. The diagnosis accuracy in malignant lymph nodes was also compared between the elastography and the standard EBUS. The value of the elastography was assessed in distinguishing the benign and malignant lymph nodes.? RESULTS: 1) The significant indicators of standard EBUS in diagnosis of malignant lymph nodes were hypoechonic nodes, uneven echo, distinct boundary and short diameter greater than 1 cm (all P<0.01). 2) There was significant difference in the elastosonography grading score between benign and malignant lymph nodes (P<0.01). 3) The elastography grading score was more sensitive and specific in determining the malignant lymph node than the standard EBUS criteria. The area under the receiver operating characteristic curve (AUC) was maximal when the elastography grading score was >=2.5. The specificity, sensitivity, positive predictive value, negative predictive value of elastography grading score was 76.9%, 85.7%, 85.7% and 76.9% in distinguishing malignant and benign nodes. The overall accuracy of elastography grading score was 82.3%. The combination of elastography grading score, low echo, distinct boundary and short diameter greater than 1 cm showed the best diagnostic efficiency value. The AUC was 0.911. In distinguishing malignant and benign nodes, the specificity, sensitivity, positive predictive value, negative predictive value and accuracy of the combined indexes was 84.6%, 88.1%, 90.2%, and 81.5% respectively. The overall accuracy was 86.8%.? CONCLUSION: The endobronchial ultrasound elastography can effectively distinguish the mediastinal and hilar lymph node metastasis in lung cancer. The diagnosis accuracy of elastography in malignant lymph node is higher than that of standard EBUS criteria. The combination of elastosonography grading score and standard EBUS criteria can improve the diagnostic efficiency. PMID- 26819424 TI - [Value of liver perfusion imaging of 256-slice CT ?in evaluation of the cirrhosis]. AB - OBJECTIVE: To investigate the value of liver perfusion imaging of 256-slice CT in evaluating the compensated and decompensated cirrhosis. ? METHODS: A total of 20 patients with liver cirrhosis, who were confirmed by liver biopsy, clinical symptoms and imaging, were selected from December 2012 to June 2014. According to the results of liver biopsy and the Child-Pugh classification, the patients were divided into a compensated cirrhosis group (n=8) and a decompensated cirrhosis group (n=12). Eleven cases without liver and spleen diseases were served as a control group. All subjects were under the 256-CT liver perfusion (256-CTP). The data of CTP [hepatic arterial perfusion (HAP), portal venous perfusion (PVP), total liver perfusion (TLP), hepatic perfusion index (HPI)] were obtained according to liver perfusion type, and the data of CTP [liver perfusion (LP), peak enhanced (PE), time to peak (TTP), blood volume (BV)] were obtained according to general perfusion type. Spearman rank correlation was used to analyze the correlation of liver cirrhosis with perfusion parameters. The receiver operating characteristic (ROC) curve was used to predict liver cirrhosis, and the maximized Youden index was served as the optimal cutoff value, then the area under curve, sensitivity and specificity were calculated.? RESULTS: The PVP, TLP and PE values in the control group, the compensated cirrhosis group and the decompensated cirrhosis group were (76.63+/-37.26), (38.78+/-16.13) and (36.14+/-?15.31) mL/(100 mL.min); (98.48+/-43.58), (55.63+/-14.47) and (54.41+/ 20.81) mL/(100 mL.min); ?(55.62+/-18.25), (44.11+/-5.79) and (41.08+/-7.74) HU, respectively, showing a gradual downward trend and a significant difference among the 3 groups (all P <0.05). HPI values were (19.50+/-6.08)%, (31.81+/-16.48)% and (34.47+/-16.04)%; TTP values were (37.32+/-8.59), (47.06+/-14.61), (59.86+/ 20.87) s, respectively, showing a gradual upward trend and significant difference among the 3 groups ( all P<0.05). There was no significant difference in the HAP, LP and BV among the 3 groups (all P>0.05). PVP, TLP, PE and LP were negatively correlated with the process of liver cirrhosis (r=-0.592, -0.567, -0.409, -0.569, all P<0.05), but HPI and TTP were positively correlated with the process of liver cirrhosis (r=0.434 and 0.538, both P<0.05). ? CONCLUSION: 256-CTP could provide useful information for the assessment of liver cirrhosis by measuring a plurality of perfusion parameters. The hepatic microvascular changes in patients with liver cirrhosis could be quantitatively assessed by perfusion CT. TTP shows high efficiency in prediction of liver cirrhosis and decompensated liver cirrhosis. PMID- 26819423 TI - [Effect of aminophylline and simvastatin on airway inflammation and mucus hypersecretion in rats with chronic obstructive pulmonary disease]. AB - OBJECTIVE: To observe the role of aminophylline and simvastatin in preventing and curing chronic obstructive pulmonary disease (COPD), and to explore the underlying mechanisms based on airway inflammation and mucus hypersecretion.? METHODS: The rat model of COPD was established by combination of cigarette smoking with intratracheal lipopolysaccharide (LPS) injection. Male SD rats were randomly divided into 4 groups (n=10 per group): a control group, a COPD group, an aminophylline group and a simvastatin group. The rats in the control group and the COPD group were treated with normal saline once a day via intragastric administration, while the rats in the aminophylline group and the simvastatin group were treated with aminophylline (5 g/L) and simvastatin (0.5 g/L) 1 mL/100 g once a day via intragastric administration, respectively. Pulmonary function and pathological changes in bronchus and lung were observed. The levels of IL-8, IL-17, and TNF-alpha in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expressions of TLR4 and mucin 5AC (MUC5AC) in bronchi and lung tissues were detected by real time PCR and Western blot, respectively.? RESULTS: Pulmonary function and the pathophysiologic changes in bronchi and lung tissues in the COPD rats were consistent with typical phenotype of COPD. Compared with the control group, lung function indexes were significantly attenuated in the COPD group, while the levels of IL-8, IL-17, and TNF-alpha in BALF as well as the mRNA and protein levels of MUC5AC and TLR4 were significantly increased. Compared with the COPD group, lung function indexes were significantly increased in the aminophylline group and simvastatin group (P<0.01), while pulmonary pathological damages, the levels of IL-8, IL-17, and TNF-alpha in BALF as well as the mRNA and protein levels of MUC5AC and TLR4 were significantly decreased (P<0.01). Compared with the aminophylline group, the peak expiratory flow as well as the levels of IL-8, IL-17, and TNF-alpha in the simvastatin group were elevated (P<0.05). There are no significant difference in the mRNA and protein levels of MUC5AC and TLR4 between the 2 groups (P>0.05).? CONCLUSION: Aminophylline and simvastatin can decrease IL-8, IL-17, and TNF-alpha levels in BALF and inhibit the expression of MUC5AC and TLR4 in airway and lung tissues in COPD rats, suggesting that they may have a preventive and therapeutic effect on COPD through reducing the airway inflammation and mucus hypersecretion. PMID- 26819425 TI - [Levels of IL-4 and IFN-gamma in serum of mice after the sheep skin acellular dermal matrix transplant]. AB - OBJECTIVE: To evaluate the immunogenicity of self-made sheep skin acellular dermal matrix (ADM).? METHODS: Both cross-linked and non-crosslinked ADMs were made after the sheep skin ADM was ready. A total of 160 healthy mice were then randomly divided into 4 groups. Group A, cross-linked ADM was implanted under skin; Group B, non-crosslinked ADM was implanted under skin; Group C, allosome skin was embedded under skin; Control group, without any implantation. Any visible changes in implantation region and any apparent rejection was recorded. Any symptoms of inflammatory reaction in implantation region were also observed by microscope. The levels of IL-4 and IFN-gamma in serum were measured on the 3rd day, 1 week, 2 weeks and 3 weeks after the operation, respectively.? RESULTS: Visual study: wound healing in implantation regions were obvious, the immunologic rejection was not significant, and the sheep ADM was absorbed gradually by ambient tissues. Microscope results: the connection between the sheep ADM and surrounding tissues was very tight with infiltration of a few inflammatory cells into the depth of sheep ADM. The structure of sheep ADM was gradually destroyed by inflammatory cells. The levels of IL-4 and IFN-gamma were not significant difference between the group of A, B or C and the control group on the 3rd day after the operation. The inflammatory reaction in implantation region of the control group degraded after 3 days, concomitant with a decrease in the levels of IL-4 and IFN-gamma. But the levels of IL-4 and IFN-gamma in the Group A, B or C remained at high level, suggesting the elevation of IL-4 and IFN-gamma levels were related to the immunologic reaction by sheep ADM. The values of IL-4/IFN gamma were significant difference between the group A, B or C and the control group at the end of the 1st week, 2nd week, and 3rd week. However, there were not significantly different among the Group A, B and C.? CONCLUSION: Sheep skin ADMs do not cause apparent rejection from mice after the transplantation because of the low immunogenicity. The cross-linked and non-crosslinked ADMs do not obviously affect the levels of IL-4 and IFN-gamma. PMID- 26819426 TI - [Relationship between serum cystatin-C levels and vibrating perception threshold in patients with ?Type 2 diabetes mellitus]. AB - OBJECTIVE: To explore the relationship between serum cystatin-C (Cys-c) levels and vibrating perception threshold (VPT) in patients with Type 2 diabetes mellitus (T2DM).? METHODS: According to the symptoms, signs and results of lab examination, a total of 352 patients with T2DM were divided into a diabetic peripheral neuropathy group (DPN group, n=107) and a non-diabetic peripheral neuropathy group (NDPN group, n=245). Serum Cys-c levels were measured by radioimmunoassay method. The relationship between serum Cys-c levels and VPT, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR), glucose and blood pressure and other parameters were also analyzed by correlation and multiple regression analysis. All T2DM patients were divided into a high Cys-c levels group (n=89) and a low Cys-c levels group (n=263) according to the upper quartile of Cys-c, and the incidence of DPN and VPT levels in each group were compared. Risk factors of DPN in T2DM patients were analyzed by binary logistic regression analysis and receiver operating characteristic (ROC) curve was used to identify the optimal cutoff of serum Cys-c levels for predicting DPN in patients with T2DM.? RESULTS: Serum Cys-c levels were significantly higher in the DPN group than that in the NDPN group [(1.04+/-0.43) vs (0.80+/-0.25) mg/L, P<0.01]. Correlation analysis showed that serum Cys-c levels were positively correlated with age, body mass index (BMI), serum creatinine (SCr), blood urea nitrogen (BUN), ACR, VPT, pulse pressure (PP), white blood cell( WBC) , red cell distribution width (RDW), hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) (r=0.410, 0.115, 0.613, 0.433, 0.291, 0.300, 0.156, 0.129, 0.282, 0.314, 0.236, respectively, P<0.05 or P<0.01); and negatively correlated with diastolic blood pressure (DBP), eGFR and indirect bilirubin (IBIL) (r=-0.135, -0.647, -0.114, respectively, P<0.05 or P<0.01). Serum Cys-c levels in T2DM patients were positively correlated with VPT after adjusting for gender, age, BMI, ACR and eGFR (r=0.235, P<0.01). Multiple regression analysis revealed that VPT, age, SCr, eGFR, PP, ACR and HbA1C were independent related factors affecting serum Cys-c levels in T2DM patients. Compared with those in the low Cys-c levels group, the prevalence rate and VPT value was increased in the high Cys-c levels group (all P<0.01). Binary logistic regression analysis found that age, Cys-c and HbA1C were independent risk factors for predicting DPN in T2DM patients (all P<0.01). ROC curve analysis revealed that the optimal cutoff of Cys-c to predict DPN in T2DM patients was 0.996 mg/L, the sensitivity was 43.9%, the specificity was 83.7%, and the area under curve was 0.663.? CONCLUSION: Serum Cys-c levels are well correlated with VPT in patients with T2DM. When the serum Cys-c levels>0.996 mg/L, the predicts have high risk of DPN in T2DM patients, which might be related to diabetic nephropathy, oxidative stress and inflammatory reaction induced by advanced age, hyperglycemia and hypertension. PMID- 26819427 TI - [Evaluation of risk factors and prognosis on diodone-induced acute kidney injury according to ESUR and KDIGO criteria]. AB - OBJECTIVE: To investigate the incidence, risk factors and prognosis for contrast induced acute kidney injury (CI-AKI) according to ESUR and KDIGO criteria in patients undergoing angiography.? METHODS: We evaluated 260 patients undergoing angiography and/or intervention therapy from April 2011 to January 2012 in the Second Xiangya Hospital of Central South University. All patients received low osmolality contrast agent (ioversol). Serum creatinine was measured before angiography or at 48 or 72 h after procedure. The multivariate logistic regression was used to analyze the risk factors of CI-AKI. The major adverse events were observed in a year of follow-up.? RESULTS: Among the 260 patients, 23 experienced CI-AKI and the incidence was 8.8% according to ESUR criteria. Twelve patients experienced CI-AKI and the incidence was 4.6% according to KDIGO criteria. The multivariate logistic regression analysis showed that diabetes mellitus and dehydration were the independent risk factors for CI-AKI according to ESUR criteria; In another KDIGO criteria, chronic kidney disease (CKD), hypercholesterolemia and diabetes mellitus were the independent risk factors for CI-AKI. The prognosis study showed that the mortality of patients with CI-AKI were significantly higher than those without CI-AKI (P<0.05).? CONCLUSION: The incidence of CI-AKI is associated with diagnostic criteria. Diabetes mellitus, CKD, dehydration and hypercholesterolemia were the independent risk factors for CI-AKI. CI-AKI is a relevant factor for mortality in a year after angiography and/or intervention therapy. PMID- 26819428 TI - [Synthetic evaluation of precancerous lesions and early esophageal cancers after endoscopic submucosal dissection]. AB - OBJECTIVE: To evaluate the safety and prognosis for patients with early esophageal cancer and precancerous lesions after endoscopic submucosal dissection (ESD).? METHODS: A total of 89 patients were admitted to the Department of internal medicine in the First People's Hospital of Anqing from August 2008 to August 2011. All patients were treated with ESD at the early stage of esophageal cancer and precancerous lesions. The patients' laboratory data and relevant medical history were collected. The postoperative complications and long-term effects of ESD were analyzed.? RESULTS: Eighty-nine patients were followed up with 100% response rate. Among 89 cases, 16 were early esophageal cancer, 38 were high-grade esophageal neoplasia and 35 were low-grade esophageal neoplasia. The one-time whole piece resection rate, complete resection rate and curative resection rate was 93.3% (84/89), 92.1% (82/89) and 92.1% (82/89), respectively. Two cases suffered intraoperative perforation with a rate of 2.2% and these 2 patients performed the intraoperative endoscopic repair; one case suffered the postoperative delayed bleeding with a rate of 1.1% and the patient underwent the conservative treatment; three cases suffered the esophageal stenosis with a rate of 3.4%. All patients were followed-up for 10-58 (36.3+/-21.2) months. In this period, one case recurred after ESD for 3 years with a rate of 1.1%; two cases were dead. The three-year survival rate was 97.8%.? CONCLUSION: The early esophageal cancer and precancerous lesions can be treated with ESD. The method is safe and the prognosis is good. PMID- 26819429 TI - [Clinical analysis of tricuspid valve replacement]. AB - OBJECTIVE: To summarize the outcome of tricuspid valve replacement.? METHODS: A total of 28 patients (15 males and 13 females) underwent tricuspid valve replacement from March 2000 to February 2015 in the First Affiliated Hospital of Zhengzhou University were recruited. Among them, 16 patients were Ebstein's anomaly, 7 had rheumatic valve heart disease, 3 and 2 suffered from infective endocarditis and degenerative tricuspid lesions, respectively.? RESULTS: One patient died of multiple organ failure. Four patients were implanted permanent cardiac pacemaker because of third degree atrioventricular block occurring in the 5th day (2 patients) and in the 9th day (2 patients) after the operation, respectively. Twenty-seven patients were followed up from 1 month to 15 years. The prosthetic valves and permanent pacemakers worked well.? CONCLUSION: Third degree of atrioventricular block, mostly appearing in early postoperative period, is the most common and severe complication of tricuspid valve replacement. The key point for prevention of damage is to accurately identify the anatomical relationship among the tricuspid valve, atrioventricular node, and conduction bundle. PMID- 26819430 TI - [Clinical analysis of prosthesis replacement for proximal humerus tumors]. AB - OBJECTIVE: To explore surgical strategies, functions and prognosis of artificial prosthesis replacement and soft tissue reconstruction for patients with invasive benign or primary malignant proximal humerus tumor.? METHODS: A total of 17 patients with invasive benign or primary malignant proximal humerus tumor underwent prosthetic replacement after segment bone tumor resection and soft tissues reconstruction from April 2007 to April 2014 were enrolled. Based on histological types, tumor stages and surgical procedures, the effects of artificial prosthesis replacement and soft tissue reconstruction on prognosis and shoulder joint function were evaluated.? RESULTS: All patients were followed up for 8 to 96 months (average time: 58.9 months). Among 11 patients with primary malignant tumor, 5 died of tumor recurrence or metastasis, and 6 showed tumor free survival for 24 to 91 months (average time: 54.83 months). The 6 patients with aggressive benign tumors survived for 39 to 96 months, with an average of 72.33 months. The shoulder joint function of 17 patients recovered to 64.88% of normal. There were significant differences in the shoulder joint function between the patients who underwent half shoulder replacement and those who underwent total shoulder replacement (56.25% vs 72.56%, P<0.05). There were significant differences in the shoulder joint function between the patients who underwent Type I A excision (retention of abductor muscles and rotator cuff) and those who underwent Type I B excision (68.75% vs 61.44%, P<0.05).? CONCLUSION: The survival of patients with invasive benign or primary malignant proximal humerus, who underwent artificial prosthesis replacement and soft tissue reconstruction, is closely related to tumor types. The shoulder joint function is associated with the methods of prosthesis replacement and soft tissue resection. PMID- 26819431 TI - [Clinical efficacy of NovaSure for 30 patients with adenomyosis]. AB - OBJECTIVE: To investigate the efficacy and safety of NovaSure system for dysmenorrhea and abnormal uterine bleeding of adenomyosis.? METHODS: A retrospective analysis on 30 patients with adenomyosis, who treated by NovaSure, were carried out. We collected related clinical data before operation and collected postoperative information about dyemenorrhea, menstruation, anemia and uterine volume by visiting outpatient or telephone.? RESULTS: All patients were followed up for 7 to 31 months after the operation. The relief rate of menstrual pain was 83.3%. All patients got obvious improvements in menstruation and anemia (P<0.05). After operation, uterine volume was significantly decreased (P<0.05). Only one case received intervention in 2 years (3.3%).? CONCLUSION: NovaSure can relieve symptoms of menorrhagia and alleviate dysmenorrhea symptoms. It is a new way for the treatment of uterine adenomyosis. PMID- 26819432 TI - [Compilation of a questionnaire on maternal and child health birth cohort study]. AB - OBJECTIVE: To compile a questionnaire on maternal and child health birth cohort study, to provide effective tools for exploring the effect of various exposure factors on pregnancy outcome and children's health, and to track children's growth and development dynamically.? METHODS: The preliminary questionnaire on maternal and child health birth cohort study was designed after literature research, health information systems analysis and group discussion. The questionnaire was finalized after expert consultation and pre-survey.? RESULTS: The formal questionnaire on maternal and child health birth cohort study was developed, including maternal health information and children's health information.? CONCLUSION: The questionnaire can be used for collecting maternal health data and children's health data within 1 year old, and this work is useful for scholars in the study on birth cohort invovling the maternal and child health. PMID- 26819433 TI - [Quality of donated liver from citizen passed away]. AB - International norms of organ transplantation mainly depends on the organ donation after the death of citizens. Numbers of studies on the quality of donated livers were conducted to reduce the early postoperative primary dysfunctions and relevant complications. The donations is based on donation after brain death (DBD) and donation after cardiac death (DCD). Hence, the differences in the quality of liver from DBD and DCD are the focus. PMID- 26819434 TI - [A case of light and heavy chain deposition disease]. AB - Monoclonal immunoglobulin deposition disease is rare in medical practice. The light and heavy chain deposition disease is characterized by deposition of monoclonal antibodies in the basement of membrane. Kidney is the most frequently involved organ. There was a male patient diagnosed as light and heavy chain deposition disease in department of Nephrology of the Second Xiangya Hospital, Central South University by renal biopsy. After treatment by oral prednisone, melphalan and thalidomide, the patient's proteinuria and serum creatinine decreased. The retrospective analysis of this case provides a guide for doctors to understand the light and heavy chain deposition disease. Early diagnosis and treatment could improve the prognosis. PMID- 26819435 TI - [To Discern the Medical Thoughts of Heo Joon, the Best Physician in Korean History--An Analysis of Disease Experiences and Treatment Cases in the Treasured Mirror of Eastern Medicine]. AB - Heo Joon is one of the best-known physicians of the Chosun Dynasty, the last imperial dynasty (1392~1910) of Korea. He had served King Seonjo () during his practice, and has produced many publications on medicine. Then, how did he actually treat the patients? So far, other than the case when he treated Gwanghaegun's smallpox, it is not clearly known how and when he attended and treated the ill. In his most famous book, the Treasured Mirror of Eastern Medicine, he details the physiopathological mechanisms, diagnoses, treatments or prescriptions, and treatment cases, however, it is not clear if they're from his own clinical experiences. Nevertheless, based on the written method, the original information is reconstituted according to its respective editors of the TMEM, a particular case being included may be considered as an agreement and acceptance of an actual treatment executed. This research analyzes what type of medicinal theory that the main writer Heo Joon employed in his real treatments, as well as how he diagnosed and treated diseases. After analyzing the complete series of the TMEM, we found a total of 301 clinical cases. Here, one may wonder, why does the Section of Inner and External Bodily Elements, that deal with diseases and the structure of the body, have far outnumber cases than the Section of Miscellaneous Disorders? Why does the TMEM introduce the various types of disease experiences and treatment cases, medical cases, simple treatments, nurturing life, materia medica, and also include supernatural phenomena? Why does the TMEM include the experiences and cases from the book published in the Song, Jin, Yuan dynasty of China, moreover in the Ming Dynasty of its time. These questions can be answered to the extent that Heo Joon and the others who participated in completing the book sought to justify the new clinical medicine practices, and because it had to be acceptable to the Confucius beliefs which dominated the society, and also because the book came to light in a time when tensions between the pre-existing Chosun medicine and the newly introduced Chinese medicine were evident. Among the clinical cases in the TMEM, there are only 41 cases that can be considered as Medical Cases which include the pathology and treatment mechanism. After analyzing these mechanisms, we were able to discover that they cover not only the theories of the 4 great physicians of Jin-Yuan Dynasty, but also the theories of the Danxi's Medical Current, a big trend in the Early Ming Dynasty, and some of the most recent clinical cases that had been just reported at the time. However, Heo Joon did not lean towards a particular theory of medicine; rather, he insisted on establishing a classical medicine based on the traditional medicinal scriptures such as the Yellow Emperor's Inner Canon or Shennong's Classic of Materia Medica, and had created his own Body-Viscera medicine, as Shin Dongwon's recent research. Moreover, he successfully secured his own right to be a clinical physician by customizing the amount of medication in prescriptions for the people of Chosun. Heo Joon was one of the chief physicians for the Royal Family of the Chosun Dynasty. Despite the tendency of traditional medicine to lean towards Taoism or Fangshu, for him the most important thing was the actual treatment of diseases. As a result, Heo Joon successfully treated smallpox by utilizing traditional medicinal methods, by breaking the taboo of not using medication on such diseases, as well as he was able to treat an unknown disease, scarlet fever, by discovering the pathological mechanism of the illness. Also he made bold decisions on altering existing prescriptions to treat diseases more efficiently. The TMEM consists of not only justified methods that integrate the different and scattered medicinal and clinical practices, which many insisted their originality, but also was backed with Heo Joon's such credible and endeavored clinical medicine. PMID- 26819436 TI - [Missionary Medicine of Canadian Presbytery and Korean Doctors under Japanese Occupation--focusing Sung-jin and Ham-heung]. AB - In East Asia during the second half of the 19th century, overseas mission work by Protestant churches thrived. Missionaries built schools and hospitals and effectively used them for evangelism. In the 20th century when Social Gospel Movement was expanding, medical work has been recognized as a significant mission service in and by itself. This article reviewed the construction and characteristics of missions work conducted by Canadian Presbytery; missionary doctors and Korean doctors who worked at the mission hospitals; why the missionary medical work had to stop; and career paths taken by Korean doctors upon liberation from Japanese occupation. The Canadian Presbytery missionaries, unlike other denomination missionaries, were rather critical of Imperial Japan, but supportive towards Koreans. This could have stemmed from the reflection of their own experience of once a colony of British Empire and also their value system that promotes egalitarian, democratic and progressive theology. The Sung jin and Ham-heung Mission Bases were a community, interacting organically as a 'Triangle of Church, School and Hospital.' The missionaries mobilized the graduates from Christian schools and organized a Young Men's Christian Association (YMCA). Some of the graduates were trained to become medical doctors or assistants and worked at mission hospitals. Missionary doctors' approaches to balancing evangelism and medical practice varied. For example, Robert Grieson went through confusion and struggled to balance conflicting roles as a pastor for evangelism and also as a physician. Kate McMillan, on the other hand, had less burden for evangelism than Grieson, and focused on medical work by taking advantage of the opportunity that, as a woman, she can easily approach Korean women. Still another case was Florence Murray who practised evangelism within the hospital setting, and successfully carried out the role as a hospital administrator, going beyond 'women's work' as McMillan did. Korean doctors and assistants who worked at the mission hospitals had seen the spread of Protestantism in their youth; had received modern education; had experienced the fall of own country in 1910 and nationwide protest against Japan in 1919. The majority of them were graduates of Severance Medical College, the hub of missionary medicine at the time. After the resignation from the mission hospitals, 80 percent of them became self-employed general practitioners. The operations of the mission hospitals began to contract in 1930 due to tightened control by Imperial Japan. Shrine worship imposed on Christians caused internal conflict and division among missionaries and brought about changes in the form and contents of the mission organization. The incidence of the assault of Dr. Grieson brought about the dissolution of Sung-jin mission base and the interruption of the operation of Je-dong Hospital. As the Pacific War expanded, missionaries were driven out of Korea and returned home. In conclusion, the missions work by Canadian Presbytery missionaries had greatly impacted Protestantism in Korea. The characteristics of Canadian Presbytery were manifested in their support of Korean nationalism movement, openness for Social Gospel, and maintaining equal footing with Korean Christians. Specifically we note the influence of these characteristics in Chosun doctors who had worked in the mission hospitals. They operated their own hospitals or clinics in a manner similar to the mission hospitals by providing treatment for poor patients free of charge or for a nominal fee and treating the patients in a kind and humanistic way. After the 1945 Liberation, Korean doctors'career paths split into two directions. most of them defected to South Korea and chose the path to work as general practitioners. A few of them remained in North Korea and became educator of new doctors. It is meaningful that former doctors of Canadian missionary hosptal became dean of 2 medical colleges among 3 of all in early North Korea. This article does not cover the comparative analysis of the medical work by the missionaries of Canadian Presbytery and other denominations. It is desirable to include this analysis of the contents and the comparison in a future study of Korean doctors who participated in the mission hospitals, by denomination and by geographical region. PMID- 26819437 TI - [Takeki Kudoh's Research on Modern Medical Science and Japanized Confucianism in Colonial Korea (Choson)]. AB - This paper reviews Kudoh Takeki's activity critically during the colonial Korea period, regarding his research on Medical Science and Japanized Confucianism. He managed 'The Seoul Gynecological Hospital'for approximately 35 years in the Choson period as a Japanese resident with Choson status. He published medical knowledge about obstetrics through more than 280 articles, and attempted to improve the hygiene and health of 'Korean Women'. He tried to complete his will toward 'One Unity of Choson and Japan'by terminating the Choson culture 'gene'as an intention. The purpose would enlighten Choson by Japanese blessing. This paper aims to confirm his intention by two aspect of analysis by 'Medical Science'as an occupation and 'Confucianism'and the background of his thought. The content of Kudoh Takeki's research in Choson regarding Medical Science-Confucianism is described as below. First, the purpose and mission of Kudoh Takeki regarding Choson was analyzed. The papers revealed the Kudoh Takeki mentioned only the 'HusbandMurders of Corean Women', which was defined by Kudoh Takeki as 'A Special Crime of Corea'. This paper examined his intensions. Second, writings by Kudoh Takeki were listed to verify the 'medical'field and 'non-medical'field according to the subject. No list of contents was found for his more than 280 articles or essays in magazines/newspapers/ publications, and these papers only described the Kudoh paper "A Special Crime of Corea"and studied the separate book publication by Kudoh THE GYNAECOLOGICAL RESEARCH OF HUSBANDMURDERS OF COREAN WOMEN, A SPECIAL CRIME OF COREA. Third, the genealogy of Confucianism of Kudoh Takeki was analyzed as his background of mental.thought by his hometown and the school he graduated from. The people from Kumamoto and Seiseiko school who were influenced by 'Yi Toegye'of Choson Confucianism were more active than general Japanese. Fourth, the practical activity of Kudoh Takeki in Choson was described. The paper revealed that his brother Tadaske and Shigeo also stayed in Choson to act as an important assistants for the Colonial Choson Government-general. Kudoh was an important man in Japanese society in Choson, acting as a member of ?Group of Same Origin? and 'Choson Association of great Asia'which was an important organization assisting Colonial Choson Government-general and was a representative position in Seoul district of Bukmichang-jeong(now Bukchang-dong) Fifth, Kudoh Takeki's precise activity to terminate Choson cultural 'gene'and lead to enlightenment was analyzed by an examination of his Medical Science as an occupation and Confucianism as a background of his thought. Even he attempted to enlighten the brutal Choson people in cultural aspects but it was only a tool to assist the colonial policy of Japan by emphasizing 'Kyoikuchokugo(Imperial Rescript on Education)'to implant the Kodo-Seishin(Imperial Spirit). Analyzing the relationship of Kumamoto Practical Party with Yi Toegye, the intention of a deep connection toward 'One Unity of Japan and Choson'by colonial policy was revealed. In conclusion, the paper revealed the Japanese modernization frame to complete 'One Unity of Japan and Choson'and 'Make people to obey the Japan Emperor'by enlightening the dark Choson and merging them with Japan as Kudoh intended. PMID- 26819438 TI - [The Construction of the Faculty of Hamheung Medical College in North Korea, 1946 48: An Unrest Coexistence of Political Ideology and Medical Expertise]. AB - This paper aims to reveal how Hamheung Medical College in North Korea kept up its faculty with the trend of a new political system. The time period consists of three series of evaluations that occurred between the start of a reformation action in 1946 and the establishment of the regime in 1948. At the time, it was difficult to secure college faculty in the medical field, because of a serious shortage of medical personnel. Moreover, the problem in the recruitment of faculty at the medical college grew bigger since the members were required to have a high level of political consciousness. Then how did Hamheung Medical College accomplish this ideal securing of faculty that possessed political ideology and medical expertise? For the first time, a faculty evaluation at the local level was carried out and got rid of a few pro-Japanese or reactionary factions but maintained most of the faculty. Although academic background and research career of the faculty were considered, securing of the manpower in terms of number was crucial for the reconstruction of a professional school level. At the second time, as the central education bureau's intervention tightened the censorship, most of the faculty were evaluated as unqualified. Indeed, it was difficult to satisfy the standard of professionalism which emphasized a high level of academic career and political thought that included affiliation of Workers' Party of North Korea. The Medical College could not find faculty that could replace those professors and therefore, most of them maintained their faculty positions. Since then, the faculty who received excellent evaluations led the school at the very front. At the third time, the Medical College itself led the evaluations and implemented more relaxed standards of political ideology and medical expertise. Faculty who were cooperative to the reformation actions that North Korea carried forward or had working experience at the hospital and health service received a high level of recognition. Accordingly, the Medical College expanded itself by securing many professors, but also embodied a large gap of academic and ideological levels between them. Hence, the political ideology and medical expertise, which were set forth as the requirements for faculty, were constructed in the space of political ideal and social reality. Despite the high criteria the North Korean Government made, Hamheung Medical College's faculty fell below the average in terms of ideological and academic standards. As a way to compensate this, professors who greatly satisfied the both virtues were placed as leaders and, for supporting them, professors who taught the general education curriculum were recruited largely. And also, it appointed a large number of medical doctors who accumulated experiences in the field as new professors. Nevertheless, the Medical College struggled to raise the quality of medical education and was unable to prevent a part of its faculty from leaving to South Korea in the time of the Korean War. Thus, the political and academic virtues of the faculty at that time were not just simply about the professor individuals but were interrelated with the medical education and health care system in North Korea. PMID- 26819439 TI - [The Korean Pharmaceutical Industry and the Expansion of the General Pharmaceuticals Market in the 1950-1960s]. AB - After the Liberation, the Korean economy was dependent on relief supplies and aid after the ruin of the colonial regime and war. The pharmaceutical business also searched for their share in the delivery of military supplies and the distribution of relief supplies. The supply-side pharmaceutical policy made the pharmaceutical market a wholesale business. The gravity of the situation led to an increased importation of medical supplies, and wholesalers took the lead in establishing the distribution structure, whereas consumers and pharmaceutical business were relatively intimidated. The aid provided by the International Cooperation Administration (ICA) marked a turning point in the Korean pharmaceutical industry after the middle of the 1950s. ICA supplied raw materials and equipment funds, while the pharmaceutical business imported advanced technology and capital. The government invited the local production of medical substances, whereas pharmaceutical businesses replaced imported medical substances with locally produced antibiotics. After the 1960s, the production of antibiotics reached saturation. Pharmaceutical businesses needed new markets to break through the stalemate, so they turned their attention to vitamins and health tonics as general pharmaceuticals, as these were suitable for mass production and mass consumption. The modernized patent medicine market after the Opening of Korea was transformed into the contemporized general pharmaceuticals market equipped with the up-to-date facilities and technology in 1960s. Pharmaceutical businesses had to advertise these new products extensively and reform the distribution structure to achieve high profits. With the introduction of TV broadcasting, these businesses invested in TV advertising and generated sizable sales figures. They also established retail pharmacy and chain stores to reform the distribution structure. The end result was a dramatic expansion of the general pharmaceuticals market. The market for vitamins and health tonics showed particularly explosive growth. As Korean industrial workers worked night and day to increase exports in the 1960s, they needed vitamins and health tonics for recovery from fatigue and to support vitality. The expansion of the general pharmaceuticals market was accompanied by increases in numbers of pharmaceutical companies. Competition intensified between pharmaceutical companies, leading some companies to search for new survival plans. The pharmaceutical industry underwent structural reform in 1960s, replacing imported medical substances with local products and inventing the new market of general pharmaceuticals. The market for vitamins and health tonics was increased, and a successful product could support a pharmaceutical company. On the contrary, a general pharmaceutical could affect the very existence of the company: if a company chased a popular product and the imitation bubble burst, then the company have lost its competitiveness in the world market. PMID- 26819440 TI - [Epidemic Cholera and American Reform Movements in the 19th Century]. AB - The 19th century was the age of great reform in American history. After constructing of the canal and railroads, the industrialization began and American society changed so rapidly. In this period, there were so many social crisis and American people tried to solve these problems within the several reform movements. These reform movements were the driving forces to control cholera during the 19th century. Cholera was the endemic disease in Bengal, India, but after the 19th century it had spread globally by the development of trade networks. The 1832 cholera in the United States was the first epidemic cholera in American history. The mortality of cholera was so high, but it was very hard to find out the cause of this fatal infectious disease. So, different social discourses happened to control epidemic cholera in the 19th century, these can be understood within the similar context of American reform movements during this period. Board of Health in New York States made a new public health act to control cholera in 1832, it was ineffective. Some people insisted that the cause of this infectious disease was the corruption of the United States. They emphasized unjust and immoral system in American society. Moral reform expanded to Nativism, because lots of Irish immigrants were the victims of cholera. So, epidemic cholera was the opportunity to spread the desire for moral reform. To control cholera in 1849, the sanitary reform in Britain had affected. The fact that it was so important to improve and maintain the water quality for the control and prevention of disease spread, the sanitary reform happened. There were two different sphere of the sanitary reform. The former was the private reform to improve sewer or privy, the latter was the public reform to build sewage facilities. The 1849 cholera had an important meaning, because the social discourse, which had emphasized the sanitation of people or home expanded to the public sphere. When cholera broke out in 1866 again, the new discourse to raise the necessity of professional medical personnel. The establishment of Metropolitan Board of Heath forced to appoint trained medical people and the treatment of disease at the home moved to medical doctors who had professional knowledge and authority. In this meaning, the medical reform provided the opportunity the appearance of professionalized medical doctors. These epidemic cholera during the 19th century, there were different reform movements in American society. The infectious disease affected development and changes of American society, the most important thing was that the problem of sanitation and public health was not only the private one, but the serious problems in society and nation. So, epidemic cholera during the 19th century provided more balanced perspective to analyze the American society in this period. PMID- 26819441 TI - Bacterial Suspensions Deposited on Microbiological Filter Material for Rapid Laser-Induced Breakdown Spectroscopy Identification. AB - Four species of bacteria, E. coli, S. epidermidis, M. smegmatis, and P. aeruginosa, were harvested from agar nutrient medium growth plates and suspended in water to create liquid specimens for the testing of a new mounting protocol. Aliquots of 30 uL were deposited on standard nitrocellulose filter paper with a mean 0.45 um pore size to create highly flat and uniform bacterial pads. The introduction of a laser-based lens-to-sample distance measuring device and a pair of matched off-axis parabolic reflectors for light collection improved both spectral reproducibility and the signal-to-noise ratio of optical emission spectra acquired from the bacterial pads by laser-induced breakdown spectroscopy. A discriminant function analysis and a partial least squares-discriminant analysis both showed improved sensitivity and specificity compared to previous mounting techniques. The behavior of the spectra as a function of suspension concentration and filter coverage was investigated, as was the effect on chemometric cell classification of sterilization via autoclaving. PMID- 26819442 TI - Effect of Sample Preparation on the Discrimination of Bacterial Isolates Cultured in Liquid Nutrient Media Using Laser-Induced Breakdown Spectroscopy (LIBS). AB - Laser-induced breakdown spectroscopy (LIBS) is used as the basis for discrimination between two genera of gram-negative bacteria and two genera of gram-positive bacteria representing pathogenic threats commonly found in poultry processing rinse waters. Because LIBS-based discrimination relies primarily upon the relative proportions of inorganic cell components including Na, K, Mg, and Ca, this study aims to determine the effects of trace mineral content and pH found in the water source used to isolate the bacteria upon the reliability of the resulting discriminant analysis. All four genera were cultured using tryptic soy agar (TSA) as the nutrient medium, and were grown under identical environmental conditions. The only variable introduced is the source water used to isolate the cultured bacteria. Cultures of each bacterium were produced using deionized (DI) water under two atmosphere conditions, reverse osmosis (RO) water, tap water, phosphate buffered saline (PBS) water, and TRIS buffered water. After 3 days of culture growth, the bacteria were centrifuged and washed three times in the same water source. Bacteria were then freeze dried, mixed with microcrystalline cellulose, and a pellet was made for LIBS analysis. Principal component analysis (PCA) was used to extract related variations in LIBS spectral data among the four bacteria genera and six water types used to isolate the bacteria, and Mahalanobis discriminant analysis (MDA) was used for classification. Results indicate not only that the four genera can be discriminated from each other in each water type, but that each genus can be discriminated by water type used for isolation. It is concluded that in order for LIBS to be a reliable and repeatable method for discrimination of bacteria grown in liquid nutrient media, care must be taken to insure that the water source used in purification of the culture be precisely controlled regarding pH, ionic strength, and proportionate amounts of mineral cations present. PMID- 26819444 TI - Application of linear mixed models to study genetic stability of height and body mass index across countries and time. AB - BACKGROUND: It is now possible to estimate genetic correlations between two independent samples when there is no overlapping phenotypic information. We applied the latest bivariate genomic methods to children in the UK and older adults in Sweden to ask two questions. Are the same variants driving individual differences in anthropometric traits in these two populations, and are these variants as important in childhood as they are later in life? METHODS: A sample of 3152 11-year-old children in the UK was compared with a sample of 6813 adults with an average age of 65 in Sweden. Genotypes were imputed from 1000 genomes with combined 9 767 136 single nucleotide polymorphisms meeting quality control criteria in both samples. Two cross-sample GCTA-GREML analyses and linkage disequilibrium (LD) score regressions were conducted to assess genetic correlations across more than 50 years: child versus adult height and child versus adult body mass index (BMI). Consistency of effects was tested using the recently proposed polygenic scoring method. RESULTS: For height, GCTA-GREML and LD score indicated strong genetic stability between children and adults, 0.58 (0.16) and 1.335 (1.09), respectively. For BMI, both methods produced similarly strong estimates of genetic stability 0.75 (0.26) and 0.855 (0.49), respectively. In height, adult polygenic score explained 60% of genetic variance in childhood and 10% of variance in BMI. CONCLUSIONS: Here we replicated and extended previous findings of longitudinal genetic stability in anthropometric traits to cross cultural dimensions, and showed that for height but not BMI these variants are as important in childhood as they are in adulthood. PMID- 26819443 TI - Early treatment of HER2-amplified brain tumors with targeted NK-92 cells and focused ultrasound improves survival. AB - BACKGROUND: Malignant brain tumors have a dismal prognosis, with residual tumor remaining after surgery necessitating adjuvant chemoradiotherapy. The blood-brain barrier hinders many chemotherapeutic agents, resulting in modest treatment efficacy. We previously demonstrated that targeted natural killer (NK)-92 cells could be delivered to desired regions of the brain using MRI-guided focused ultrasound and Definity microbubbles. Targeted NK-92 cells have advantages over many systemic therapies including their specific cytotoxicity to malignant cells (particularly those expressing the target antigen), ability to spare healthy cells, and being unaffected by efflux channels. METHODS: We investigated whether longitudinal treatments with targeted NK-92 cells, focused ultrasound, and microbubbles could slow tumor growth and improve survival in an orthotopic HER2 amplified rodent brain tumor model using a human breast cancer line as a prototype. The HER2 receptor, involved in cell growth and differentiation, is expressed by both primary and metastatic brain tumors. Breast cancers with HER2 amplification have a higher risk of CNS metastasis and poorer prognosis. RESULTS: Early intensive treatment with targeted NK-92 cells and ultrasound improved survival compared with biweekly treatments or either treatment alone. The intensive treatment paradigm resulted in long-term survival in 50% of subjects. CONCLUSIONS: Many tumor proteins could be exploited for targeted therapy with the NK-92 cell line; combined with the mounting safety evidence for transcranial ultrasound, these results may soon be translatable to a highly targeted treatment option for patients with brain tumors. PMID- 26819445 TI - Patient assessment of diabetes care in a pay-for-performance program. AB - OBJECTIVE: Few studies address quality of care in pay-for-performance (P4P) programs from the perspective of patients' perceptions. This study aimed to examine and compare the patient assessment of diabetes chronic care as perceived by diabetic patients enrolled and not enrolled in a P4P program from the patients' self-reported perspectives. DESIGN: A cross-sectional study with case and comparison group design. SETTING: A large-scale survey was conducted from February to November 2013 in 18 healthcare institutions in Taiwan. PARTICIPANTS: A total of 1458 P4P (n = 1037) and non-P4P (n = 421) diabetic patients participated in this large survey. The Chinese version of the Patient Assessment of Chronic Illness Care (PACIC) instrument was used and patients' clinical outcome data (e.g. HbA1c, LDL) were collected. INTERVENTION: None. MAIN OUTCOME MEASURES: Five subscales from the PACIC were measured, including patient activation, delivery system design/system support, goal setting/tailoring, problem solving/contextual and follow-up/coordination. Patient clinical outcomes were also measured. Multiple linear regression and logistic regression models were used and controlled for patient demographic and health institution characteristics statistically. RESULTS: After adjusting for covariates, P4P patients had higher overall scores on the PACIC and five subscales than non-P4P patients. P4P patients also had better clinical processes of care (e.g. HbA1c test) and intermediate outcomes. CONCLUSIONS: Patients who participated in the program likely received better patient-centered care given the original Chronic Care Model. Better perceptions of diabetic care assessment also better clinical outcomes. The PACIC instrument can be used for the patient assessment of chronic care in a P4P program. PMID- 26819446 TI - Preliminary experience with Precipitating Hydrophobic Injectable Liquid (PHIL) in treating cerebral AVMs. AB - OBJECTIVE: To describe our early experience in treating cerebral arteriovenous malformations (AVMs) with the new Precipitating Hydrophobic Injectable Liquid (PHIL) embolic material. MATERIALS AND METHODS: Between June and August 2015 five patients with cerebral AVMs were treated at two tertiary university hospitals. PHIL was used as complementary treatment to Onyx liquid embolic material or as the sole endovascular treatment. RESULTS: Five patients (average age 39 years (range 19-73)) with ruptured plexiform AVMs were treated. The group included one patient with Spetzler-Martin grade II AVMs, three grade III, and one grade IV. One grade II and two grade III AVMs were cured. A total of nine pedicles were embolized with an average of two pedicles per session. There were no procedural complications. One patient had a seizure after embolization but a brain CT scan showed no hemorrhage. CONCLUSIONS: PHIL is a new embolic agent that can be used for the treatment of cerebral AVMs. PMID- 26819447 TI - Unwanted detachment of the Solitaire device during mechanical thrombectomy in acute ischemic stroke. AB - BACKGROUND: The use of retrievable stents for endovascular clot retrieval has dramatically improved successful revascularization and clinical outcome in selected patients with acute stroke. OBJECTIVE: To describe the rate and clinical consequences of unwanted spontaneous detachment of these devices during mechanical thrombectomy. METHODS: We studied 262 consecutive patients treated with the retrievable stent, Solitaire, for acute ischemic stroke between November 2008 and April 2015. Clinical, procedural, and outcome variables were compared between patients with and without unexpected detachment of this device. Detachment was classified as proximal to the stent proximal marker (type A) or distal to the marker (type B). Poor functional outcome was defined as modified Rankin scale score >2 at 90 days. RESULTS: Unwanted detachment occurred in 6/262 (2.3%) cases, four of type A and two of type B. Stent recovery was possible in three patients, all of 'type A', but in none of 'type B'. The number of prior passes was higher in patients with undesired detachment (3 (2-5) vs 2 (1-3), p=0.007). Detachment was associated with higher rate of symptomatic intracranial hemorrhage (SICH) (33.3% vs 4.3%, p=0.001), poorer outcome (100% vs 54.8%, p=0.028), and higher mortality rate at 90 days (50% vs 17%, p=0.038). CONCLUSIONS: Unwanted detachment of a Solitaire is an uncommon complication during mechanical thrombectomy in patients with acute ischemic stroke and is associated with the clot retrieval attempts, SICH, poor outcome, and higher mortality. PMID- 26819448 TI - Intravascular optical coherence tomography for the evaluation of arterial bifurcations covered by flow diverters. AB - BACKGROUND AND OBJECTIVE: Due to its high spatial resolution, intravascular optical coherence tomography (OCT) has been used as a valid method for in vivo evaluation of several types of coronary stents at straight lumen and bifurcation sites. We sought to evaluate its effectiveness for flow diverting stents deployed in arterial bifurcation sites involving jailing of a side branch. METHODS: Four large white swine were stented with flow diverting stents covering the right common carotid artery-ascending pharyngeal artery bifurcation. After 12 weeks of follow-up the animals were evaluated by digital subtraction angiography and intravascular OCT and subsequently sacrificed. Neointimal thickness on the parent arteries and the free segments of the stent were measured. The stented arteries were harvested and underwent scanning electron microscopy (SEM) imaging. Ostia surface values were measured with OCT three-dimensional (3D) reconstructions and SEM images. RESULTS: All endovascular procedures and OCT pullback runs were feasible. Stent apposition was satisfactory on the immediate post-stent OCT reconstructions. At 12-week controls, all stents and jailed branches were patent. Mean neointimal thickness was 0.11+/-0.04 mm on the free segments of the stent. The mean ostia surface at 12 weeks was 319 750+/-345 533 MUm2 with 3D-OCT reconstructions and 351 198+/-396 355 MUm2 with SEM image-derived calculations. Good correlation was found for ostia surface values between the two techniques; the values did not differ significantly in this preliminary study. CONCLUSIONS: Intravascular OCT appears to be a promising technique for immediate and follow-up assessment of the orifice of arterial branches covered by flow diverting stents. PMID- 26819449 TI - Pan-Cancer Immunogenomic Perspective on the Tumor Microenvironment Based on PD-L1 and CD8 T-Cell Infiltration. AB - PURPOSE: There is currently no reliable biomarker to predict who would benefit from anti-PD-1/PD-L1 inhibitors. We comprehensively analyzed the immunogenomic properties in The Cancer Genome Atlas (TCGA) according to the classification of tumor into four groups based on PD-L1 status and tumor-infiltrating lymphocyte recruitment (TIL), a combination that has been suggested to be a theoretically reliable biomarker of anti-PD-1/PD-L1 inhibitors. EXPERIMENTAL DESIGN: The RNA expression levels of PD-L1 and CD8A in the samples in the pan-cancer database of TCGA (N = 9,677) were analyzed. Based on their median values, the samples were classified into four tumor microenvironment immune types (TMIT). The mutational profiles, PD-L1 amplification, and viral association of the samples were compared according to the four TMITs. RESULTS: The proportions of TMIT I, defined by high PD-L1 and CD8A expression, were high in lung adenocarcinoma (67.1%) and kidney clear cell carcinoma (64.8%) among solid cancers. The number of somatic mutations and the proportion of microsatellite instable-high tumor in TMIT I were significantly higher than those in other TMITs, respectively (P < 0.001). PD-L1 amplification and oncogenic virus infection were significantly associated with TMIT I, respectively (P < 0.001). A multivariate analysis confirmed that the number of somatic mutations, PD-L1 amplification, and Epstein-Barr virus/human papillomavirus infection were independently associated with TMIT I. CONCLUSIONS: TMIT I is associated with a high mutational burden, PD-L1 amplification, and oncogenic viral infection. This integrative analysis highlights the importance of the assessment of both PD-L1 expression and TIL recruitment to predict responders to immune checkpoint inhibitors. Clin Cancer Res; 22(9); 2261-70. (c)2016 AACRSee related commentary by Schalper et al., p. 2102. PMID- 26819450 TI - NDUFA4L2 Fine-tunes Oxidative Stress in Hepatocellular Carcinoma. AB - PURPOSE: Hepatocellular carcinoma (HCC) lacks effective curative therapy. Hypoxia is commonly found in HCC. Hypoxia elicits a series of protumorigenic responses through hypoxia-inducible factor-1 (HIF1). Better understanding of the metabolic adaptations of HCC cells during hypoxia is essential to the design of new therapeutic regimen. EXPERIMENTAL DESIGN: Expressions of genes involved in the electron transport chain (ETC) in HCC cell lines (20% and 1% O2) and human HCC samples were analyzed by transcriptome sequencing. Expression of NDUFA4L2, a less active subunit in complex I of the ETC, in 100 pairs of HCC and nontumorous liver tissues were analyzed by qRT-PCR. Student t test and Kaplan-Meier analyses were used for clinicopathologic correlation and survival studies. Orthotopic HCC implantation model was used to evaluate the efficiency of HIF inhibitor. RESULTS: NDUFA4L2 was drastically overexpressed in human HCC and induced by hypoxia. NDUFA4L2 overexpression was closely associated with tumor microsatellite formation, absence of tumor encapsulation, and poor overall survival in HCC patients. We confirmed that NDUFA4L2 was HIF1-regulated in HCC cells. Inactivation of HIF1/NDUFA4L2 increased mitochondrial activity and oxygen consumption, resulting in ROS accumulation and apoptosis. Knockdown of NDUFA4L2 markedly suppressed HCC growth and metastasis in vivo HIF inhibitor, digoxin, significantly suppressed growth of tumors that expressed high level of NDUFA4L2. CONCLUSIONS: Our study has provided the first clinical relevance of NDUFA4L2 in human cancer and suggested that HCC patients with NDUFA4L2 overexpression may be suitable candidates for HIF inhibitor treatment. Clin Cancer Res; 22(12); 3105 17. (c)2016 AACR. PMID- 26819451 TI - Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study. AB - PURPOSE: Next-generation sequencing (NGS) has detailed the genomic characterization of diffuse large B-cell lymphoma (DLBCL) by identifying recurrent somatic mutations. We set out to design a clinically feasible NGS panel focusing on genes whose mutations hold potential therapeutic impact. Furthermore, for the first time, we evaluated the prognostic value of these mutations in prospective clinical trials. EXPERIMENTAL DESIGN: A Lymphopanel was designed to identify mutations in 34 genes, selected according to literature and a whole exome sequencing study of relapsed/refractory DLBCL patients. The tumor DNA of 215 patients with CD20(+)de novo DLBCL in the prospective, multicenter, and randomized LNH-03B LYSA clinical trials was sequenced to deep, uniform coverage with the Lymphopanel. Cell-of-origin molecular classification was obtained through gene expression profiling with HGU133+2.0 Affymetrix GeneChip arrays. RESULTS: The Lymphopanel was informative for 96% of patients. A clear depiction of DLBCL subtype molecular heterogeneity was uncovered with the Lymphopanel, confirming that activated B-cell-like (ABC), germinal center B-cell like (GCB), and primary mediastinal B-cell lymphoma (PMBL) are frequently affected by mutations in NF-kappaB, epigenetic, and JAK-STAT pathways, respectively. Novel truncating immunity pathway, ITPKB, MFHAS1, and XPO1 mutations were identified as highly enriched in PMBL. Notably, TNFAIP3 and GNA13 mutations in ABC patients treated with R-CHOP were associated with significantly less favorable prognoses. CONCLUSIONS: This study demonstrates the contribution of NGS with a consensus gene panel to personalized therapy in DLBCL, highlighting the molecular heterogeneity of subtypes and identifying somatic mutations with therapeutic and prognostic impact. Clin Cancer Res; 22(12); 2919-28. (c)2016 AACRSee related commentary by Lim and Elenitoba-Johnson, p. 2829. PMID- 26819452 TI - Molecular Pathways: Isocitrate Dehydrogenase Mutations in Cancer. AB - IDH1 and IDH2 are homodimeric enzymes that catalyze the conversion of isocitrate to alpha-ketoglutarate (alpha-KG) and concomitantly produce reduced NADPH from NADP(+) Mutations in the genes encoding IDH1 and IDH2 have recently been found in a variety of human cancers, most commonly glioma, acute myeloid leukemia (AML), chondrosarcoma, and intrahepatic cholangiocarcinoma. The mutant protein loses its normal enzymatic activity and gains a new ability to produce the "oncometabolite" R(-)-2-hydroxyglutarate (R-2-HG). R-2-HG competitively inhibits alpha-KG dependent enzymes which play crucial roles in gene regulation and tissue homeostasis. Expression of mutant IDH impairs cellular differentiation in various cell lineages and promotes tumor development in cooperation with other cancer genes. First-generation inhibitors of mutant IDH have entered clinical trials, and have shown encouraging results in patients with IDH-mutant AML. This article summarizes recent progress in our understanding of the role of mutant IDH in tumorigenesis.Clin Cancer Res; 22(8); 1837-42. (c)2016 AACR. PMID- 26819454 TI - Brain BDNF expression as a biomarker for cognitive reserve against Alzheimer disease progression. PMID- 26819453 TI - The Addition of the BTK Inhibitor Ibrutinib to Anti-CD19 Chimeric Antigen Receptor T Cells (CART19) Improves Responses against Mantle Cell Lymphoma. AB - PURPOSE: Responses to therapy with chimeric antigen receptor T cells recognizing CD19 (CART19, CTL019) may vary by histology. Mantle cell lymphoma (MCL) represents a B-cell malignancy that remains incurable despite novel therapies such as the BTK inhibitor ibrutinib, and where data from CTL019 therapy are scant. Using MCL as a model, we sought to build upon the outcomes from CTL019 and from ibrutinib therapy by combining these in a rational manner. EXPERIMENTAL DESIGN: MCL cell lines and primary MCL samples were combined with autologous or normal donor-derived anti-CD19 CAR T cells along with ibrutinib. The effect of the combination was studied in vitro and in mouse xenograft models. RESULTS: MCL cells strongly activated multiple CTL019 effector functions, and MCL killing by CTL019 was further enhanced in the presence of ibrutinib. In a xenograft MCL model, we showed superior disease control in the CTL019- as compared with ibrutinib-treated mice (median survival not reached vs. 95 days, P < 0.005) but most mice receiving CTL019 monotherapy eventually relapsed. Therefore, we added ibrutinib to CTL019 and showed that 80% to 100% of mice in the CTL019 + ibrutinib arm and 0% to 20% of mice in the CTL019 arm, respectively, remained in long-term remission (P < 0.05). CONCLUSIONS: Combining CTL019 with ibrutinib represents a rational way to incorporate two of the most recent therapies in MCL. Our findings pave the way to a two-pronged therapeutic strategy in patients with MCL and other types of B-cell lymphoma. Clin Cancer Res; 22(11); 2684-96. (c)2016 AACR. PMID- 26819455 TI - An investigation into the psychosocial effects of the postictal state. AB - OBJECTIVE: To determine whether postictal cognitive and behavioral impairment (PCBI) is independently associated with specific aspects of a patient's psychosocial health in those with epilepsy and nonepileptic events. METHODS: We used the University of Calgary's Comprehensive Epilepsy Clinic prospective cohort database to identify patients reporting PCBI. The cohort was stratified into those diagnosed with epilepsy or nonepileptic events at first clinic visit. Univariate comparisons and stepwise multiple logistic regression with backward elimination method were used to identify factors associated with PCBI for individuals with epilepsy and those with nonepileptic events. We then determined if PCBI was independently associated with depression and the use of social assistance when controlling for known risk factors. RESULTS: We identified 1,776 patients, of whom 1,510 (85%) had epilepsy and 235 had nonepileptic events (13%). PCBI was independently associated with depression in those with epilepsy (odds ratio [OR] 1.73; 95% confidence interval [CI] 1.06-2.83; p = 0.03) and with the need for social assistance in those with nonepileptic events (OR 4.81; 95% CI 2.02-11.42; p < 0.001). CONCLUSIONS: PCBI appears to be significantly associated with differing psychosocial outcomes depending on the patient's initial diagnosis. Although additional research is necessary to examine causality, our results suggest that depression and employment concerns appear to be particularly important factors for patients with PCBI and epilepsy and nonepileptic attacks, respectively. PMID- 26819456 TI - Cerebral perfusion in stroke-like migraine attacks after radiation therapy syndrome. PMID- 26819457 TI - Higher brain BDNF gene expression is associated with slower cognitive decline in older adults. AB - OBJECTIVES: We tested whether brain-derived neurotrophic factor (BDNF) gene expression levels are associated with cognitive decline in older adults. METHODS: Five hundred thirty-five older participants underwent annual cognitive assessments and brain autopsy at death. BDNF gene expression was measured in the dorsolateral prefrontal cortex. Linear mixed models were used to examine whether BDNF expression was associated with cognitive decline adjusting for age, sex, and education. An interaction term was added to determine whether this association varied with clinical diagnosis proximate to death (no cognitive impairment, mild cognitive impairment, or dementia). Finally, we examined the extent to which the association of Alzheimer disease (AD) pathology with cognitive decline varied by BDNF expression. RESULTS: Higher brain BDNF expression was associated with slower cognitive decline (p < 0.001); cognitive decline was about 50% slower with the 90th percentile BDNF expression vs 10th. This association was strongest in individuals with dementia. The level of BDNF expression was lower in individuals with pathologic AD (p = 0.006), but was not associated with macroscopic infarcts, Lewy body disease, or hippocampal sclerosis. BDNF expression remained associated with cognitive decline in a model adjusting for age, sex, education, and neuropathologies (p < 0.001). Furthermore, the effect of AD pathology on cognitive decline varied by BDNF expression such that the effect was strongest for high levels of AD pathology (p = 0.015); thus, in individuals with high AD pathology (90th percentile), cognitive decline was about 40% slower with the 90th percentile BDNF expression vs 10th. CONCLUSIONS: Higher brain BDNF expression is associated with slower cognitive decline and may also reduce the deleterious effects of AD pathology on cognitive decline. PMID- 26819458 TI - GPi vs STN deep brain stimulation for Parkinson disease: Three-year follow-up. AB - OBJECTIVE: To compare motor symptoms, cognition, mood, and behavior 3 years after deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) in advanced Parkinson disease (PD). METHODS: Patients with PD eligible for DBS were randomized to bilateral GPi DBS and bilateral STN DBS (1:1). The primary outcome measures were (1) improvement in motor symptoms in off-drug phase measured with the Unified Parkinson Disease Rating Scale (UPDRS) and (2) a composite score for cognitive, mood, and behavioral effects, and inability to complete follow-up at 36 months after surgery. RESULTS: Of the 128 patients enrolled, 90 were able to complete the 3-year follow-up. We found significantly more improvement of motor symptoms after STN DBS (median [interquartile range (IQR)] at 3 years, GPi 33 [23-41], STN 28 [20-36], p = 0.04). No between-group differences were observed on the composite score (GPi 83%, STN 86%). Secondary outcomes showed larger improvement in off-drug functioning in the AMC Linear Disability Scale score after STN DBS (mean +/- SD, GPi 65.2 +/- 20.1, STN 72.6 +/- 18.0, p = 0.05). Medication was reduced more after STN DBS (median levodopa equivalent dose [IQR] at 3 years, GPi 1,060 [657 1,860], STN 605 [411-875], p < 0.001). No differences in adverse effects were recorded, apart from more reoperations to a different target after GPi DBS (GPi n = 8, STN n = 1). CONCLUSIONS: Off-drug phase motor symptoms and functioning improve more after STN DBS than after GPi DBS. No between-group differences were observed on a composite score for cognition, mood, and behavior, and the inability to participate in follow-up. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that STN DBS provides more off-phase motor improvement than GPi DBS, but with a similar risk for cognitive, mood, and behavioral complications. PMID- 26819459 TI - Risk factors for probable REM sleep behavior disorder: A community-based study. AB - OBJECTIVE: To examine risk factors for REM sleep behavior disorder (RBD) in a large-scale community-based study. METHODS: This community-based study included 12,784 Chinese adults (10,556 men and 2,228 women, aged 24 years or older) who were free of Parkinson disease and dementia in 2012. Probable RBD (pRBD) status was determined by a validated questionnaire (Chinese RBD questionnaire-Hong Kong) in 2012. Potential risk factors-including age, sex, smoking, socioeconomic status, physical activity, obesity, consumption of tea (surrogate for caffeine intake) and alcohol, serum concentrations of lipids and glucose, and chronic disease status-were assessed in 2006. Logistic regression was used to calculate odds ratios and 95% confidence intervals and to test differences in prevalence of pRBD across exposures. RESULTS: Prevalence of pRBD was 5.9% in men and 4.1% in women. In the fully adjusted model, risk factors that were significantly associated with a higher risk of having pRBD included lower education level, coal mining and other blue collar occupation, lower physical activity level, diabetes or prediabetes, lower body mass index, head injury, higher low-density lipoprotein level, and chronic olfactory and taste dysfunction. In sensitivity analyses, restricting to pRBD cases with symptom onset within 1 year or excluding coal miners or those with history of head injury generated similar results. CONCLUSION: We found several potential risk factors for pRBD, including socioeconomic status, head injury, olfactory and taste dysfunction, and various cardiovascular risk factors. Future prospective studies to establish the temporal relationship between these potential risk factors and RBD are warranted. PMID- 26819460 TI - Emerging Roles of PCSK9: More Than a One-Trick Pony. PMID- 26819462 TI - The Plot Thickens Further for Type I Interferons in Atherosclerotic Disease. PMID- 26819461 TI - LRP in Endothelial Cells: A Little Goes a Long Way. PMID- 26819463 TI - APOL1 Variants: From Parasites to Kidney Function to Cardiovascular Disease. PMID- 26819464 TI - A Nuclear Attack on Thrombosis and Inflammation. PMID- 26819465 TI - Role for Hyaluronan Synthase 3 in the Response to Vascular Injury. PMID- 26819467 TI - Correction. PMID- 26819468 TI - Correction. PMID- 26819469 TI - FILTUS: a desktop GUI for fast and efficient detection of disease-causing variants, including a novel autozygosity detector. AB - FILTUS is a stand-alone tool for working with annotated variant files, e.g. when searching for variants causing Mendelian disease. Very flexible in terms of input file formats, FILTUS offers efficient filtering and a range of downstream utilities, including statistical analysis of gene sharing patterns, detection of de novo mutations in trios, quality control plots and autozygosity mapping. The autozygosity mapping is based on a hidden Markov model and enables accurate detection of autozygous regions directly from exome-scale variant files. AVAILABILITY AND IMPLEMENTATION: FILTUS is written in Python and runs on Windows, Mac and Linux. Binaries and source code are freely available at http://folk.uio.no/magnusv/filtus.html and on GitHub: https://github.com/magnusdv/filtus Automatic installation is available via PyPI (e.g. pip install filtus). CONTACT: magnusdv@medisin.uio.no SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26819466 TI - Systems Biology and Noninvasive Imaging of Atherosclerosis. PMID- 26819470 TI - Differential methylation analysis for BS-seq data under general experimental design. AB - MOTIVATION: DNA methylation is an epigenetic modification with important roles in many biological processes and diseases. Bisulfite sequencing (BS-seq) has emerged recently as the technology of choice to profile DNA methylation because of its accuracy, genome coverage and higher resolution. Current statistical methods to identify differential methylation mainly focus on comparing two treatment groups. With an increasing number of experiments performed under a general and multiple factor design, particularly in reduced representation bisulfite sequencing, there is a need to develop more flexible, powerful and computationally efficient methods. RESULTS: We present a novel statistical model to detect differentially methylated loci from BS-seq data under general experimental design, based on a beta-binomial regression model with 'arcsine' link function. Parameter estimation is based on transformed data with generalized least square approach without relying on iterative algorithm. Simulation and real data analyses demonstrate that our method is accurate, powerful, robust and computationally efficient. AVAILABILITY AND IMPLEMENTATION: It is available as Bioconductor package DSS. CONTACT: yongpark@pitt.edu or hao.wu@emory.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26819471 TI - On the discovery of hospital admission patterns-a clarification. AB - CONTACT: ognjen.arandjelvoic@gmail.com. PMID- 26819472 TI - Unipept web services for metaproteomics analysis. AB - Unipept is an open source web application that is designed for metaproteomics analysis with a focus on interactive datavisualization. It is underpinned by a fast index built from UniProtKB and the NCBI taxonomy that enables quick retrieval of all UniProt entries in which a given tryptic peptide occurs. Unipept version 2.4 introduced web services that provide programmatic access to the metaproteomics analysis features. This enables integration of Unipept functionality in custom applications and data processing pipelines. AVAILABILITY AND IMPLEMENTATION: The web services are freely available at http://api.unipept.ugent.be and are open sourced under the MIT license. CONTACT: Unipept@ugent.be SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26819473 TI - BioCircos.js: an interactive Circos JavaScript library for biological data visualization on web applications. AB - We here present BioCircos.js, an interactive and lightweight JavaScript library especially for biological data interactive visualization. BioCircos.js facilitates the development of web-based applications for circular visualization of various biological data, such as genomic features, genetic variations, gene expression and biomolecular interactions. AVAILABILITY AND IMPLEMENTATION: BioCircos.js and its manual are freely available online at http://bioinfo.ibp.ac.cn/biocircos/ CONTACT: rschen@ibp.ac.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26819474 TI - Galaxy Portal: interacting with the galaxy platform through mobile devices. AB - : We present Galaxy Portal app, an open source interface to the Galaxy system through smart phones and tablets. The Galaxy Portal provides convenient and efficient monitoring of job completion, as well as opportunities for inspection of results and execution history. In addition to being useful to the Galaxy community, we believe that the app also exemplifies a useful way of exploiting mobile interfaces for research/high-performance computing resources in general. AVAILABILITY AND IMPLEMENTATION: The source is freely available under a GPL license on GitHub, along with user documentation and pre-compiled binaries and instructions for several platforms: https://github.com/Tarostar/QMLGalaxyPortal It is available for iOS version 7 (and newer) through the Apple App Store, and for Android through Google Play for version 4.1 (API 16) or newer. CONTACT: geirksa@ifi.uio.no. PMID- 26819475 TI - Jumonji Domain Containing Protein 6 Is Decreased in Human Preeclamptic Placentas and Regulates sFLT-1 Splice Variant Production. AB - The anti-angiogenic protein, soluble fms-like tyrosine kinase-1 (sFLT-1), plays a central role in preeclamptic pathophysiology. A splice variant of FLT-1 (VEGF receptor 1), sFLT-1 is released in excessive amounts from the preeclamptic placenta into the maternal circulation, where it causes endothelial dysfunction manifesting as end-organ disease. However, the mechanisms regulating its production within the placenta remain poorly understood. Recently it was shown in endothelial cells that Jumonji domain containing protein 6 (JMJD6) hydroxylates U2 small nuclear ribonucleoprotein auxiliary factor 65-kDa subunit (U2AF65, a component of the splicesome). The hydroxylation by JMJD6 is oxygen dependent. Under hypoxia, JMJD6 is less able to hydroxylate U2AF65, and this unhydroxylated form of U2AF65 biases splicing of FLT-1 to sFLT-1. We assessed whether oxygen sensing JMJD6 is differentially expressed in preeclamptic placenta and regulates sFLT-1 splicing in placenta via U2AF65. JMJD6 protein expression was significantly reduced in preterm preeclamptic placenta (P < 0.0001; n = 21) relative to preterm controls (n = 10). Exposing both placental and endothelial cells to hypoxia significantly reduced JMJD6 mRNA and increased sFLT-1 mRNA and protein expression. Silencing JMJD6 in primary endothelial and trophoblast cells significantly increased sFLT-1 secretion. Next, we examined whether these molecules may be directly interacting. We demonstrated that placental U2AF65 colocalized with JMJD6. In turn, we found JMJD6 directly interacts with U2AF65, which in turn produces sFLT-1 mRNA transcripts. Taken together, our findings provide evidence that JMJD6 may play a role in regulating the production of sFLT 1 in the preeclamptic placenta. Decreased placental JMJD6 expression may be an important component to the pathophysiology of preeclampsia. PMID- 26819476 TI - Extracellular Vesicles Originate from the Conceptus and Uterus During Early Pregnancy in Sheep. AB - Cells release diverse types of membrane-bound vesicles of endosomal and plasma membrane origin, termed exosomes and microvesicles, respectively. Extracellular vesicles (EVs) represent an important mode of intercellular communication by transferring select RNAs, proteins, and lipids between cells. The present studies tested the hypothesis that the elongating ovine conceptus and uterus produces EVs that mediate conceptus-maternal interactions during early pregnancy. In Study 1, EVs were purified from uterine luminal fluid of Day 14 cyclic sheep. The EVs were fluorescently labeled with PKH67 dye and infused into the uterine lumen of pregnant sheep for 6 days using an osmotic pump. On Day 14, labeled EVs were observed in the conceptus trophectoderm and uterine epithelia, but not in the uterine stroma or myometrium. In Study 2, Day 14 conceptuses were cultured ex vivo for 24 h and found to release EVs into the culture medium. Proteomics analysis of the Day 14 conceptus-derived EVs identified 231 proteins that were enriched for extracellular space and several protein classes, including proteases, protease inhibitors, chaperones and chaperonins. RNA sequencing of Day 14 conceptus-derived EVs detected expression of 512 mRNAs. The top-expressed genes were overrepresented in ribosomal functions and components. Isolated EVs from conceptuses were fluorescently labeled with PKH67 and infused into the uterine lumen of cyclic sheep for 6 days using an osmotic pump. On Day 14, labeled EVs were observed in the uterine epithelia, but not in the uterine stroma or myometrium. Labeled EVs were not observed in the ovary or in other maternal tissues. These studies support the ideas that EVs emanate from both the conceptus trophectoderm and uterine epithelia, and are involved in intercellular communication between those cells during the establishment of pregnancy in sheep. PMID- 26819477 TI - Synthetic Steroid Hormones Regulated Cell Proliferation Through MicroRNA-34a-5p in Human Ovarian Endometrioma. AB - Endometriosis is the hormone-dependent product of endometrial tissue found outside the uterus. Recently, micro-RNAs (miRNAs) were shown to play a role in endometriotic lesion development. However, the mechanism of steroid hormones responsible for miRNA remains obscure. In the present study, we assayed for the effects of synthetic steroid hormones (danazol, progesterone, and medroxyprogesterone acetate [MPA]) on miRNAs in endometriosis. We used a global miRNA expression profile microarray to evaluate miRNA expression in endometrial mesenchymal stem cells (EN-MSCs) of ovarian endometrioma following treatment with 1 MUM danazol, progesterone, or MPA. Furthermore, we selected candidate miRNAs whose expression changed more than fivefold and compared the effects of danazol, progesterone, and MPA treatments and also compared those results with controls in EN-MSCs. Among those with a fivefold change, we found 13 ectopically upregulated miRNAs in EN-MSCs. To understand the function of these 13 miRNAs, we subjected their sequences to Ingenuity Pathway Analysis. According to both the etiology and pathogenesis of endometriosis, we found that miR-199a-5p and miR-34a-5p showed specific association with the disease, including molecular and cellular functions. Steroid hormone treatment elevated the levels of miR-199a-5p and miR 34a-5p. An inhibitor of miR-34a-5p also reduced the synthetic steroid hormones effects on cell proliferation. In vivo data revealed that miRNA levels in endometriotic lesions correlated with findings following in vitro synthetic hormone treatment. Our data show the effects of synthetic steroid hormones on miRNA regulation. These findings contribute to our understanding of the molecular impact of the synthetic steroid hormones and suggest a potential mechanism for endometriosis treatment. PMID- 26819479 TI - Toll-like Receptors 4 and 5 Cooperatively Initiate the Innate Immune Responses to Uropathogenic Escherichia coli Infection in Mouse Epididymal Epithelial Cells. AB - Uropathogenic Escherichia coli (UPEC) may cause epididymitis and impair male fertility. The mechanisms underlying the innate immune responses to UPEC infection in the epididymis are not fully understood. This study showed that UPEC induced innate immune responses in mouse epididymal epithelial cells (EECs) through the activation of Toll-like receptor 4 (TLR4) and TLR5. Infection with UPEC significantly induced the expression of proinflammatory cytokines, including tumor necrosis factor alpha, interleukin 6, and monocyte chemoattractant protein 1, in EECs through the activation of nuclear factor kappa B. Moreover, UPEC induced the production of type 1 interferons by EECs through the activation of interferon regulatory factor 3. The UPEC-induced innate immune responses were significantly reduced in the EECs of Tlr4 or Tlr5 knockout mice. The innate immune responses were further reduced in Tlr4 and Tlr5 double-knockout EECs. Furthermore, we demonstrated that TLR4 and TLR5 cooperatively initiated the epididymal innate immune responses to UPEC infection in vivo. The results provide novel insights into the mechanisms underlying the epididymal innate immune responses to UPEC infection. PMID- 26819478 TI - A Specific Transitory Increase in Intracellular Calcium Induced by Progesterone Promotes Acrosomal Exocytosis in Mouse Sperm. AB - During capacitation, sperm acquire the ability to undergo the acrosome reaction (AR), an essential step in fertilization. Progesterone produced by cumulus cells has been associated with various physiological processes in sperm, including stimulation of AR. An increase in intracellular Ca(2+) ([Ca(2+)]i) is necessary for AR to occur. In this study, we investigated the spatiotemporal correlation between the changes in [Ca(2+)]i and AR in single mouse spermatozoa in response to progesterone. We found that progesterone stimulates an [Ca(2+)]i increase in five different patterns: gradual increase, oscillatory, late transitory, immediate transitory, and sustained. We also observed that the [Ca(2+)]i increase promoted by progesterone starts at either the flagellum or the head. We validated the use of FM4-64 as an indicator for the occurrence of the AR by simultaneously detecting its fluorescence increase and the loss of EGFP in transgenic EGFPAcr sperm. For the first time, we have simultaneously visualized the rise in [Ca(2+)]i and the process of exocytosis in response to progesterone and found that only a specific transitory increase in [Ca(2+)]i originating in the sperm head promotes the initiation of AR. PMID- 26819481 TI - Augmented composite likelihood for copula modeling in family studies under biased sampling. AB - The heritability of chronic diseases can be effectively studied by examining the nature and extent of within-family associations in disease onset times. Families are typically accrued through a biased sampling scheme in which affected individuals are identified and sampled along with their relatives who may provide right-censored or current status data on their disease onset times. We develop likelihood and composite likelihood methods for modeling the within-family association in these times through copula models in which dependencies are characterized by Kendall's [Formula: see text] Auxiliary data from independent individuals are exploited by augmentating composite likelihoods to increase precision of marginal parameter estimates and consequently increase efficiency in dependence parameter estimation. An application to a motivating family study in psoriatic arthritis illustrates the method and provides some evidence of excessive paternal transmission of risk. PMID- 26819482 TI - Asymmetric intergroup bullying: The enactment and maintenance of societal inequality at work. AB - What does inequality mean for dysfunctional organizational behaviours, such as workplace bullying? This article argues that workplace bullying can be understood as a manifestation of intergroup dynamics originating beyond the organization. We introduce the construct of asymmetric intergroup bullying: the disproportionate mistreatment of members of low status groups, with the intended effect of enhancing the subordination of that group in society at large. Analysis of data from 38 interviews with public and private sector workers in Turkey depicts a pattern of asymmetric intergroup bullying, undertaken to achieve organizational and broader sociopolitical goals. Respondents reported bullying acts used to get rid of unwanted personnel, with the goal of avoiding severance pay, or of removing supporters of the former government from positions of political and economic influence. Bullying was also described as working towards the dominance of the sociocultural worldview of one political group over another. We discuss asymmetric intergroup bullying as one mechanism through which acute intergroup hierarchy in the broader society corrupts management practice and employee interactions, in turn exacerbating economic inequality along group lines. PMID- 26819484 TI - Low Temperature Plasma Causes Double-Strand Break DNA Damage in Primary Epithelial Cells Cultured from a Human Prostate Tumour. AB - Research in the new field of plasma medicine continues to demonstrate the efficacy of low temperature plasmas for numerous biomedical applications. Responses such as reduction in cell viability and cell death for cancer therapy, cell proliferation for wound healing, and bacterial inactivation have been observed as a result of plasma treatment. In this study we applied low temperature plasma to prostate cancer primary cells and tissue to inflict irreparable DNA damage. PMID- 26819483 TI - Anatomically accurate high resolution modeling of human whole heart electromechanics: A strongly scalable algebraic multigrid solver method for nonlinear deformation. AB - Electromechanical (EM) models of the heart have been used successfully to study fundamental mechanisms underlying a heart beat in health and disease. However, in all modeling studies reported so far numerous simplifications were made in terms of representing biophysical details of cellular function and its heterogeneity, gross anatomy and tissue microstructure, as well as the bidirectional coupling between electrophysiology (EP) and tissue distension. One limiting factor is the employed spatial discretization methods which are not sufficiently flexible to accommodate complex geometries or resolve heterogeneities, but, even more importantly, the limited efficiency of the prevailing solver techniques which are not sufficiently scalable to deal with the incurring increase in degrees of freedom (DOF) when modeling cardiac electromechanics at high spatio-temporal resolution. This study reports on the development of a novel methodology for solving the nonlinear equation of finite elasticity using human whole organ models of cardiac electromechanics, discretized at a high para-cellular resolution. Three patient-specific, anatomically accurate, whole heart EM models were reconstructed from magnetic resonance (MR) scans at resolutions of 220 MUm, 440 MUm and 880 MUm, yielding meshes of approximately 184.6, 24.4 and 3.7 million tetrahedral elements and 95.9, 13.2 and 2.1 million displacement DOF, respectively. The same mesh was used for discretizing the governing equations of both electrophysiology (EP) and nonlinear elasticity. A novel algebraic multigrid (AMG) preconditioner for an iterative Krylov solver was developed to deal with the resulting computational load. The AMG preconditioner was designed under the primary objective of achieving favorable strong scaling characteristics for both setup and solution runtimes, as this is key for exploiting current high performance computing hardware. Benchmark results using the 220 MUm, 440 MUm and 880 MUm meshes demonstrate efficient scaling up to 1024, 4096 and 8192 compute cores which allowed the simulation of a single heart beat in 44.3, 87.8 and 235.3 minutes, respectively. The efficiency of the method allows fast simulation cycles without compromising anatomical or biophysical detail. PMID- 26819485 TI - Impact of Childhood Maltreatment on Recidivism in Youth Offenders: A Matched Control Study. AB - The purpose of the study is to examine the impact of childhood maltreatment on youth offender recidivism in Singapore. The study used case file coding on a sample of 3,744 youth offenders, among whom about 6% had a childhood maltreatment history. The results showed that the Youth Level of Service/Case Management Inventory 2.0 (YLS/CMI 2.0) ratings significantly predicted recidivism for nonmaltreated youth offenders, but not for maltreated youth offenders. Using propensity score matching, the result from a Cox regression analysis showed that maltreated youth offenders were 1.38 times as likely as their nonmaltreated counterparts to reoffend with a follow-up period of up to 7.4 years. The results implied that the YLS/CMI 2.0 measures were insufficient for assessing the risk for recidivism for the maltreated youth offenders, and that other information is needed to help assessors use the professional override when making the overall risk ratings. PMID- 26819486 TI - Some new analysis results for a class of interface problems. AB - Interface problems modeled by differential equations have many applications in mathematical biology, fluid mechanics, material sciences, and many other areas. Typically, interface problems are characterized by discontinuities in the coefficients and/or the Dirac delta function singularities in the source term. Due to these irregularities, solutions to the differential equations are not smooth or discontinuous. In this paper, some new results on the jump conditions of the solution across the interface are derived using the distribution theory and the theory of weak solutions. Some theoretical results on the boundary singularity in which the singular delta function is at the boundary are obtained. Finally, the proof of the convergency of the Immersed Boundary method is presented. The IB method is shown to be first order convergent in Linfinity norm. PMID- 26819487 TI - Measuring afterschool program quality using setting-level observational approaches. AB - As the importance of afterschool hours for youth development is widely acknowledged, afterschool settings have recently received increasing attention as an important venue for youth interventions. A range of intervention programs have been in place, generally aiming at positive youth development through enhancing the quality of programs. A growing need has thus arisen for reliable and valid measures of afterschool quality. This study examined the extent to which the two observational tools, i.e., Caregiver Interaction Scales (CIS) and Promising Practices Rating Scales (PPRS), could serve as reliable and valid tools for assessing the various dimensions of afterschool setting quality. The study shows the potential promise of the instruments, on the one hand, and suggests future directions for improvement of measurement design and development of the field, on the other hand. In particular, our findings suggest the importance of addressing the effect of day-to-day fluctuations in observed afterschool quality. PMID- 26819488 TI - Incorporating Corrections for the Head-Holder and Compensation Filter when Calculating Skin Dose during Fluoroscopically-Guided Interventions. AB - The skin dose tracking system (DTS) that we developed provides a color-coded illustration of the cumulative skin dose distribution on a 3D graphic of the patient during fluoroscopic procedures for immediate feedback to the interventionist. To improve the accuracy of dose calculation, we now have incorporated two additional important corrections (1) for the holder used to immobilize the head in neuro-interventions and (2) for the built-in compensation filters used for beam equalization. Both devices have been modeled in the DTS software so that beam intensity corrections can be made. The head-holder is modeled as two concentric hemi-cylindrical surfaces such that the path length between those surfaces can be determined for rays to individual points on the skin surface. The head-holder on the imaging system we used was measured to attenuate the primary x-rays by 10 to 20% for normal incidence, and up to 40% at non-normal incidence. In addition, three compensation filters of different shape are built into the collimator apparatus and were measured to have attenuation factors ranging from 58% to 99%, depending on kVp and beam filtration. These filters can translate and rotate in the beam and their motion is tracked by the DTS using the digital signal from the imaging system. When it is determined that a ray to a given point on the skin passes through the compensation filter, the appropriate attenuation correction is applied. These corrections have been successfully incorporated in the DTS software to provide a more accurate determination of skin dose. PMID- 26819489 TI - A three-camera imaging microscope for high-speed single-molecule tracking and super-resolution imaging in living cells. AB - Our aim is to develop quantitative single-molecule assays to study when and where molecules are interacting inside living cells and where enzymes are active. To this end we present a three-camera imaging microscope for fast tracking of multiple interacting molecules simultaneously, with high spatiotemporal resolution. The system was designed around an ASI RAMM frame using three separate tube lenses and custom multi-band dichroics to allow for enhanced detection efficiency. The frame times of the three Andor iXon Ultra EMCCD cameras are hardware synchronized to the laser excitation pulses of the three excitation lasers, such that the fluorophores are effectively immobilized during frame acquisitions and do not yield detections that are motion-blurred. Stroboscopic illumination allows robust detection from even rapidly moving molecules while minimizing bleaching, and since snapshots can be spaced out with varying time intervals, stroboscopic illumination enables a direct comparison to be made between fast and slow molecules under identical light dosage. We have developed algorithms that accurately track and co-localize multiple interacting biomolecules. The three-color microscope combined with our co-movement algorithms have made it possible for instance to simultaneously image and track how the chromosome environment affects diffusion kinetics or determine how mRNAs diffuse during translation. Such multiplexed single-molecule measurements at a high spatiotemporal resolution inside living cells will provide a major tool for testing models relating molecular architecture and biological dynamics. PMID- 26819490 TI - Clinical Applications of Hemolytic Markers in the Differential Diagnosis and Management of Hemolytic Anemia. AB - Several hemolytic markers are available to guide the differential diagnosis and to monitor treatment of hemolytic conditions. They include increased reticulocytes, an indicator of marrow compensatory response, elevated lactate dehydrogenase, a marker of intravascular hemolysis, reduced haptoglobin, and unconjugated hyperbilirubinemia. The direct antiglobulin test is the cornerstone of autoimmune forms, and blood smear examination is fundamental in the diagnosis of congenital membrane defects and thrombotic microangiopathies. Marked increase of lactate dehydrogenase and hemosiderinuria are typical of intravascular hemolysis, as observed in paroxysmal nocturnal hemoglobinuria, and hyperferritinemia is associated with chronic hemolysis. Prosthetic valve replacement and stenting are also associated with intravascular and chronic hemolysis. Compensatory reticulocytosis may be inadequate/absent in case of marrow involvement, iron/vitamin deficiency, infections, or autoimmune reaction against bone marrow-precursors. Reticulocytopenia occurs in 20-40% of autoimmune hemolytic anemia cases and is a poor prognostic factor. Increased reticulocytes, lactate dehydrogenase, and bilirubin, as well as reduced haptoglobin, are observed in conditions other than hemolysis that may confound the clinical picture. Hemoglobin defines the clinical severity of hemolysis, and thrombocytopenia suggests a possible thrombotic microangiopathy or Evans' syndrome. A comprehensive clinical and laboratory evaluation is advisable for a correct diagnostic and therapeutic workup of the different hemolytic conditions. PMID- 26819491 TI - Significant Association of HLA-B Alleles and Genotypes in Thai Children with Autism Spectrum Disorders: A Case-Control Study. AB - Autism is a severe neurodevelopmental disorder. Many susceptible causative genes have been identified. Most of the previous reports showed the relationship between the Human Leukocyte Antigen (HLA) gene and etiology of autism. In order to identify HLA-B alleles associated with autism in Thai population, we compared the frequency of HLA-B allele in 364 autistic subjects with 952 normal subjects by using a two-stage sequence-specific oligonucleotide probe system (PCR-SSOP) method based on flow-cytometry technology. HLA-B (*) 13:02 (P = 0.019, OR = 2.229), HLA-B (*) 38:02 (P = 0.049, OR = 1.628), HLA-B (*) 44:03 (P = 0.016, OR = 1.645), and HLA-B (*) 56:01 (P = 1.78 * 10(-4), OR = 4.927) alleles were significantly increased in autistic subjects compared with normal subjects. Moreover, we found that the HLA-B (*) 18:02 (P = 0.016, OR = 0.375) and HLA-B (*) 46:12 (P = 0.008, OR = 0.147) alleles were negatively associated with autism when compared to normal controls. Both alleles might have a protective role in disease development. In addition, four HLA-B genotypes of autistic patients had statistically significant relationship with control groups, consisting of HLA-B (*) 3905/(*) 5801 (P = 0.032, OR = 24.697), HLA-B (*) 2704/(*) 5801 (P = 0.022, OR = 6.872), HLA-B (*) 3501/(*) 4403 (P = 0.021, OR = 30.269), and HLA-B (*) 1801/(*) 4402 (P = 0.017, OR = 13.757). This is the first report on HLA-B associated with Thai autism and may serve as a marker for genetic susceptibility to autism in Thai population. PMID- 26819492 TI - African American Children At-Risk of Increasingly Conflicted Teacher-Student Relationships in Elementary School. AB - Previous studies found different trajectories of conflicted relationships with teachers predictive of academic underachievement. However, little is known about what places children at risk for atypical conflict trajectories. This follow-up study examines whether African American ethnicity, IQ, and SES are unique predictors of teacher-student conflict trajectories taking into account sociobehavioral predictors, including aggression and prosocial behavior. The study included the same ethnically diverse sample of 657 academically at-risk children in which previously four latent growth classes of conflict trajectories (grades 1-5) predictive of underachievement were identified. In this follow-up study, 6 predictors were examined: African American ethnicity, SES, IQ (independent assessment), Inhibitory control (performance measure), and Aggression and Prosocial behavior (peer assessment). The results demonstrated that African American ethnicity, but not IQ and SES, uniquely predicted atypical conflict trajectories, while controlling for sociobehavioral predictors. African American children were at risk of increasingly conflicted relationships with elementary school teachers, which has been found to increase the risk of academic underachievement in middle school. PMID- 26819493 TI - REEF: Retainable Evaluator Execution Framework. AB - Resource Managers like Apache YARN have emerged as a critical layer in the cloud computing system stack, but the developer abstractions for leasing cluster resources and instantiating application logic are very low-level. This flexibility comes at a high cost in terms of developer effort, as each application must repeatedly tackle the same challenges (e.g., fault-tolerance, task scheduling and coordination) and re-implement common mechanisms (e.g., caching, bulk-data transfers). This paper presents REEF, a development framework that provides a control-plane for scheduling and coordinating task-level (data plane) work on cluster resources obtained from a Resource Manager. REEF provides mechanisms that facilitate resource re-use for data caching, and state management abstractions that greatly ease the development of elastic data processing work flows on cloud platforms that support a Resource Manager service. REEF is being used to develop several commercial offerings such as the Azure Stream Analytics service. Furthermore, we demonstrate REEF development of a distributed shell application, a machine learning algorithm, and a port of the CORFU [4] system. REEF is also currently an Apache Incubator project that has attracted contributors from several instititutions. PMID- 26819494 TI - Robust Full-Motion Recovery of Head by Dynamic Templates and Re-registration Techniques. AB - This paper presents a method to recover the full-motion (3 rotations and 3 translations) of the head from an input video using a cylindrical head model. Given an initial reference template of the head image and the corresponding head pose, the head model is created and full head motion is recovered automatically. The robustness of the approach is achieved by a combination of three techniques. First, we use the iteratively re-weighted least squares (IRLS) technique in conjunction with the image gradient to accommodate non-rigid motion and occlusion. Second, while tracking, the templates are dynamically updated to diminish the effects of self-occlusion and gradual lighting changes and to maintain accurate tracking even when the face moves out of view of the camera. Third, to minimize error accumulation inherent in the use of dynamic templates, we re-register images to a reference template whenever head pose is close to that in the template. The performance of the method, which runs in real time, was evaluated in three separate experiments using image sequences (both synthetic and real) for which ground truth head motion was known. The real sequences included pitch and yaw as large as 40 degrees and 75 degrees , respectively. The average recovery accuracy of the 3D rotations was about 3 degrees . In a further test, the method was used as part of a facial expression analysis system intended for use with spontaneous facial behavior in which moderate head motion is common. Image data consisted of 1-minute of video from each of 10 subjects while engaged in a 2-person interview. The method successfully stabilized face and eye images allowing for 98% accuracy in automatic blink recognition. PMID- 26819496 TI - Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes. AB - Rheumatoid arthritis (RA) is characterized by inflammatory cell infiltration, fibroblast-like synoviocytes (FLS) invasive proliferation, and joint destruction. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces immune activation. In this study, we examined whether cGAS plays a role in RA FLS. In this study, cGAS was overexpressed in RA-FLS compared with OA FLS. TNFalpha stimulation induced cGAS expression in RA FLS. Overexpression of cGAS promoted the proliferation and knockdown of cGAS inhibited the proliferation of RA FLS. cGAS overexpression enhanced the production of proinflammatory cytokines and matrix metalloproteinases (MMPs) as well as AKT and ERK phosphorylation in TNFalpha-stimulated FLS. In contrast, cGAS silencing inhibited production of proinflammatory cytokines and matrix metalloproteinases (MMPs) as well as AKT and ERK phosphorylation in TNFalpha-stimulated FLS. These results suggest that cGAS activates the AKT and ERK pathways to promote the inflammatory response of RA FLS, and the development of strategies targeting cGAS may have therapeutic potential for human RA. PMID- 26819495 TI - 4-Isopropyl-2,6-bis(1-phenylethyl)aniline 1, an Analogue of KTH-13 Isolated from Cordyceps bassiana, Inhibits the NF-kappaB-Mediated Inflammatory Response. AB - The Cordyceps species has been a good source of compounds with anticancer and anti-inflammatory activities. Recently, we reported a novel compound (4-isopropyl 2,6-bis(1-phenylethyl)phenol, KTH-13) with anticancer activity isolated from Cordyceps bassiana and created several derivatives to increase its pharmacological activity. In this study, we tested one of the KTH-013 derivatives, 4-isopropyl-2,6-bis(1-phenylethyl)aniline 1 (KTH-13-AD1), with regard to anti-inflammatory activity under macrophage-mediated inflammatory conditions. KTH-13-AD1 clearly suppressed the production of nitric oxide (NO) and reactive oxygen species (ROS) in lipopolysaccharide (LPS) and sodium nitroprusside- (SNP-) treated macrophage-like cells (RAW264.7 cells). Similarly, this compound also reduced mRNA expression of inducible NO synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha), as analyzed by RT-PCR and real-time PCR. Interestingly, KTH-13-AD1 strongly diminished NF-kappaB-mediated luciferase activities and nuclear translocation of NF-kappaB family proteins. In accordance, KTH-13-AD1 suppressed the upstream signaling pathway of NF-kappaB activation, including IkappaBalpha, IKKalpha/beta, AKT, p85/PI3K, and Src in a time- and dose dependent manner. The autophosphorylation of Src and NF-kappaB observed during the overexpression of Src was also suppressed by KTH-13-AD1. These results strongly suggest that KTH-13-AD1 has strong anti-inflammatory features mediated by suppression of the Src/NF-kappaB regulatory loop. PMID- 26819497 TI - Resistance to P. brasiliensis Experimental Infection of Inbred Mice Is Associated with an Efficient Neutrophil Mobilization and Activation by Mediators of Inflammation. AB - Paracoccidioidomycosis (PCM) is a systemic fungal infection, endemic in Brazil, that leads to severe morbidity and even mortality if not correctly treated. Patients may respond differently to PCM depending on the pattern of the acquired immune response developed. The onset of protective immune response is notably mediated by neutrophils (PMN) that play an important role through directly killing the fungi and also by interacting with other cell types to modulate the acquired protective immune response that may follow. In that way, this study aimed to present and compare different experimental models of PCM (intraperitoneal and subcutaneous) regarding PMN production and maturation inside femoral bone marrow and also PMN infiltration in peritoneal and subcutaneous exudates of resistant and susceptible mice. We also assessed the fungal colony forming units and the levels of soluble inflammatory mediators (LTB4, KC, IFN gamma, GM-CSF, and IL-10) inside subcutaneous air-pouches to compare the efficiency of the PMN present at this site in relation to the two main neutrophil functions: initial lysis of the invading pathogen and modulation of the acquired immune response. P. brasiliensis inoculated intraperitoneally was able to disseminate to the bone marrow of susceptible mice, causing a more marked alteration of PMN production and maturation than that observed after resistant mice infection by the same route. Subcutaneous air-pouch inoculation of P. brasiliensis elicited a controlled and limited infection that produced a PMN-rich exudate, thus favoring the study of the interaction between the fungus and the neutrophils. Susceptible mice produced higher numbers of PMN; however, these cells were less effective in killing the fungi. Inflammatory cytokines were more pronounced in resistant mice, which supports their PCM raised resistance. PMID- 26819498 TI - Clinical Use of Tolerogenic Dendritic Cells-Harmonization Approach in European Collaborative Effort. AB - The number of patients with autoimmune diseases and severe allergies and recipients of transplants increases worldwide. Currently, these patients require lifelong administration of immunomodulatory drugs. Often, these drugs are expensive and show immediate or late-occurring severe side effects. Treatment would be greatly improved by targeting the cause of autoimmunity, that is, loss of tolerance to self-antigens. Accumulating knowledge on immune mechanisms has led to the development of tolerogenic dendritic cells (tolDC), with the specific objective to restrain unwanted immune reactions in the long term. The first clinical trials with tolDC have recently been conducted and more tolDC trials are underway. Although the safety trials have been encouraging, many questions relating to tolDC, for example, cell-manufacturing protocols, administration route, amount and frequency, or mechanism of action, remain to be answered. Aiming to join efforts in translating tolDC and other tolerogenic cellular products (e.g., Tregs and macrophages) to the clinic, a European COST (European Cooperation in Science and Technology) network has been initiated-A FACTT (action to focus and accelerate cell-based tolerance-inducing therapies). A FACTT aims to minimize overlap and maximize comparison of tolDC approaches through establishment of minimum information models and consensus monitoring parameters, ensuring that progress will be in an efficient, safe, and cost-effective way. PMID- 26819499 TI - Elevated Plasma IL-38 Concentrations in Patients with Acute ST-Segment Elevation Myocardial Infarction and Their Dynamics after Reperfusion Treatment. AB - OBJECTIVE: Recent studies suggest that IL-38 is associated with autoimmune diseases. Furthermore, IL-38 is expressed in human atheromatous plaque. However, the plasma levels of IL-38 in patients with ST-segment elevation myocardial infarction (STEMI) have not yet to be investigated. METHODS: On admission, at 24 h, at 48 h, and at 7 days, plasma IL-38, C-reactive protein (CRP), cardiac troponin I (cTNI), and N-terminal of the prohormone brain natriuretic peptide (NT proBNP) levels were measured and IL-38 gene in peripheral blood mononuclear cells (PBMCs) was detected in STEMI patients. RESULTS: The results showed that plasma IL-38 levels and IL-38 gene expression in PBMCs were significantly increased in STEMI patients compared with control group and were time dependent, peaked at 24 h. In addition, plasma IL-38 levels were dramatically reduced in patients with reperfusion treatment compared with control group. Similar results were also demonstrated with CRP, cTNI, and NT-proBNP levels. Furthermore, IL-38 levels were found to be positively correlated with CRP, cTNI, and NT-proBNP and be weakly negatively correlated with left ventricular ejection fraction (LVEF) in STEMI patients. CONCLUSIONS: The results indicate that circulating IL-38 is a potentially novel biomarker for patients with STEMI and IL-38 might be a new target for MI study. PMID- 26819500 TI - Neutrophilic Bronchial Inflammation Correlates with Clinical and Functional Findings in Patients with Noncystic Fibrosis Bronchiectasis. AB - Background. Neutrophilic bronchial inflammation is a main feature of bronchiectasis, but not much is known about its relationship with other disease features. Aim. To compare airway inflammatory markers with clinical and functional findings in subjects with stable noncystic fibrosis bronchiectasis (NCFB). Methods. 152 NFCB patients (62.6 years; females: 57.2%) underwent clinical and functional cross-sectional evaluation, including microbiologic and inflammatory cell profile in sputum, and exhaled breath condensate malondialdehyde (EBC-MDA). NFCB severity was assessed using BSI and FACED criteria. Results. Sputum neutrophil percentages inversely correlated with FEV1 (P < 0.0001; rho = -0.428), weakly with Leicester Cough Questionnaire score (P = 0.068; rho = -0.58), and directly with duration of the disease (P = 0.004; rho = 0.3) and BSI severity score (P = 0.005; rho = 0.37), but not with FACED. Sputum neutrophilia was higher in colonized subjects, P. aeruginosa colonized subjects showing greater sputum neutrophilia and lower FEV1. Patients with >=3 exacerbations in the last year showed a significantly greater EBC-MDA than the remaining patients. Conclusions. Sputum neutrophilic inflammation and biomarkers of oxidative stress in EBC can be considered good biomarkers of disease severity in NCFB patients, as confirmed by pulmonary function, disease duration, bacterial colonization, BSI score, and exacerbation rate. PMID- 26819501 TI - Levo-Tetrahydropalmatine Attenuates Bone Cancer Pain by Inhibiting Microglial Cells Activation. AB - OBJECTIVE: The present study is to investigate the analgesic roles of L-THP in rats with bone cancer pain caused by tumor cell implantation (TCI). METHODS: Thermal hyperalgesia and mechanical allodynia were measured at different time points before and after operation. L-THP (20, 40, and 60 mg/kg) were administrated intragastrically at early phase of postoperation (before pain appearance) and later phase of postoperation (after pain appearance), respectively. The concentrations of TNF-alpha, IL-1beta, and IL-18 in spinal cord were measured by enzyme-linked immunosorbent assay. Western blot was used to test the activation of astrocytes and microglial cells in spinal cord after TCI treatment. RESULTS: TCI treatment induced significant thermal hyperalgesia and mechanical allodynia. Administration of L-THP at high doses significantly prevented and/or reversed bone cancer-related pain behaviors. Besides, TCI induced activation of microglial cells and the increased levels of TNF-alpha and IL-18 were inhibited by L-THP administration. However, L-THP failed to affect TCI induced astrocytes activation and IL-1beta increase. CONCLUSION: This study suggests the possible clinical utility of L-THP in the treatment of bone cancer pain. The analgesic effects of L-THP on bone cancer pain maybe underlying the inhibition of microglial cells activation and proinflammatory cytokines increase. PMID- 26819502 TI - Is irritable bowel syndrome an infectious disease? AB - Irritable bowel syndrome (IBS) is the most common of all gastroenterological diseases. While many mechanisms have been postulated to explain its etiology, no single mechanism entirely explains the heterogeneity of symptoms seen with the various phenotypes of the disease. Recent data from both basic and clinical sciences suggest that underlying infectious disease may provide a unifying hypothesis that better explains the overall symptomatology. The presence of small intestinal bowel overgrowth (SIBO) has been documented in patients with IBS and reductions in SIBO as determined by breath testing correlate with IBS symptom improvement in clinical trials. The incidence of new onset IBS symptoms following acute infectious gastroenteritis also suggests an infectious cause. Alterations in microbiota-host interactions may compromise epithelial barrier integrity, immune function, and the development and function of both central and enteric nervous systems explaining alterations in the brain-gut axis. Clinical evidence from treatment trials with both probiotics and antibiotics also support this etiology. Probiotics appear to restore the imbalance in the microflora and improve IBS-specific quality of life. Antibiotic trials with both neomycin and rifaximin show improvement in global IBS symptoms that correlates with breath test normalization in diarrhea-predominant patients. The treatment response to two weeks of rifaximin is sustained for up to ten weeks and comparable results are seen in symptom reduction with retreatment in patients who develop recurrent symptoms. PMID- 26819503 TI - Molecular genetics and targeted therapeutics in biliary tract carcinoma. AB - The primary malignancies of the biliary tract, cholangiocarcinoma and gallbladder cancer, often present at an advanced stage and are marginally sensitive to radiation and chemotherapy. Accumulating evidence indicates that molecularly targeted agents may provide new hope for improving treatment response in biliary tract carcinoma (BTC). In this article, we provide a critical review of the pathogenesis and genetic abnormalities of biliary tract neoplasms, in addition to discussing the current and emerging targeted therapeutics in BTC. Genetic studies of biliary tumors have identified the growth factors and receptors as well as their downstream signaling pathways that control the growth and survival of biliary epithelia. Target-specific monoclonal antibodies and small molecules inhibitors directed against the signaling pathways that drive BTC growth and invasion have been developed. Numerous clinical trials designed to test these agents as either monotherapy or in combination with conventional chemotherapy have been completed or are currently underway. Research focusing on understanding the molecular basis of biliary tumorigenesis will continue to identify for targeted therapy the key mutations that drive growth and invasion of biliary neoplasms. Additional strategies that have emerged for treating this malignant disease include targeting the epigenetic alterations of BTC and immunotherapy. By integrating targeted therapy with molecular profiles of biliary tumor, we hope to provide precision treatment for patients with malignant diseases of the biliary tract. PMID- 26819504 TI - Hepatic non-parenchymal cells: Master regulators of alcoholic liver disease? AB - Chronic alcohol consumption is one of the most common causes of the progression of alcoholic liver disease (ALD). In the past, alcohol-mediated hepatocyte injury was assumed to be a significantly major cause of ALD. However, a huge number of recent and brilliant studies have demonstrated that hepatic non-parenchymal cells including Kupffer cells, hepatic stellate cells, liver sinusoidal endothelial cells and diverse types of lymphocytes play crucial roles in the pathogenesis of ALD by producing inflammatory mediators such as cytokines, oxidative stress, microRNA, and lipid-originated metabolites (retinoic acid and endocannabinoids) or by directly interacting with parenchymal cells (hepatocytes). Therefore, understanding the comprehensive roles of hepatic non-parenchymal cells during the development of ALD will provide new integrative directions for the treatment of ALD. This review will address the roles of non-parenchymal cells in alcoholic steatosis, inflammation, and liver fibrosis and might help us to discover possible therapeutic targets and treatments involving modulating the non parenchymal cells in ALD. PMID- 26819505 TI - Liver pathology of hepatitis C, beyond grading and staging of the disease. AB - Liver biopsy evaluation plays a critical role in management of patients with viral hepatitis C. In patients with acute viral hepatitis, a liver biopsy, though uncommonly performed, helps to rule out other non-viral causes of deranged liver function. In chronic viral hepatitis C, it is considered the gold standard in assessment of the degree of necroinflammation and the stage of fibrosis, to help guide treatment and determine prognosis. It also helps rule out any concomitant diseases such as steatohepatitis, hemochromatosis or others. In patients with chronic progressive liver disease with cirrhosis and dominant nodules, a targeted liver biopsy is helpful in differentiating a regenerative nodule from dysplastic nodule or hepatocellular carcinoma. In the setting of transplantation, the liver biopsy helps distinguish recurrent hepatitis C from acute rejection and also is invaluable in the diagnosis of fibrosing cholestatic hepatitis, a rare variant of recurrent hepatitis C. This comprehensive review discusses the entire spectrum of pathologic findings in the course of hepatitis C infection. PMID- 26819506 TI - Chronic hepatitis C virus infection: Serum biomarkers in predicting liver damage. AB - Currently, a major clinical challenge in the management of the increasing number of hepatitis C virus (HCV) infected patients is determining the best means for evaluating liver impairment. Prognosis and treatment of chronic hepatitis C (CHC) are partly dependent on the assessment of histological activity, namely cell necrosis and inflammation, and the degree of liver fibrosis. These parameters can be provided by liver biopsy; however, in addition to the risks related to an invasive procedure, liver biopsy has been associated with sampling error mostly due to suboptimal biopsy size. To avoid these pitfalls, several markers have been proposed as non-invasive alternatives for the diagnosis of liver damage. Distinct approaches among the currently available non-invasive methods are (1) the physical ones based on imaging techniques; and (2) the biological ones based on serum biomarkers. In this review, we discuss these approaches with special focus on currently available non-invasive serum markers. We will discuss: (1) class I serum biomarkers individually and as combined panels, particularly those that mirror the metabolism of liver extracellular matrix turnover and/or fibrogenic cell changes; (2) class II biomarkers that are indirect serum markers and are based on the evaluation of common functional alterations in the liver; and (3) biomarkers of liver cell death, since hepatocyte apoptosis plays a significant role in the pathogenesis of HCV infection. We highlight in this review the evidence behind the use of these markers and assess the diagnostic accuracy as well as advantages, limitations, and application in clinical practice of each test for predicting liver damage in CHC. PMID- 26819508 TI - Analysis of peripheral blood dendritic cells as a non-invasive tool in the follow up of patients with chronic hepatitis C. AB - Hepatitis C virus (HCV) has a high propensity to establish chronic infections. Failure of HCV-infected individuals to activate effective antiviral immune responses is at least in part related to HCV-induced impairment of dendritic cells (DCs) that play a central role in activating T cell responses. Although the impact of HCV on DC phenotype and function is likely to be more prominent in the liver, major HCV-induced alterations are detectable in peripheral blood DCs (pbDCs) that represent the most accessible source of DCs. These alterations include numerical reduction, impaired production of inflammatory cytokines and increased production of immunosuppressive IL10. These changes in DCs are relevant to our understanding the immune mechanisms underlying the propensity of HCV to establish persistent infection. Importantly, the non-invasive accessibility of pbDCs renders the analysis of these cells a convenient procedure that can be serially repeated in patient follow-up. Accordingly, the study of pbDCs in HCV infected patients during conventional treatment with pegylated interferon and ribavirin indicated that restoration of normal plasmacytoid DC count may represent an additional mechanism contributing to the efficacy of the dual therapy. It also identified the pre-treatment levels of plasmacytoid DCs and IL10 as putative predictors of response to therapy. Treatment of chronic HCV infection is changing, as new generation direct-acting antiviral agents will soon be available for use in interferon-free therapeutic strategies. The phenotypic and functional analysis of pbDCs in this novel therapeutic setting will provide a valuable tool for investigating mechanisms underlying treatment efficacy and for identifying predictors of treatment response. PMID- 26819507 TI - Vertically acquired hepatitis C virus infection: Correlates of transmission and disease progression. AB - The worldwide prevalence of hepatitis C virus (HCV) infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injections still remain important routes of infection. After the screening of blood donors, mother-to child transmission (MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance (SVC) that usually occurs within 6 years of life. IL 28B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare. PMID- 26819509 TI - Rheumatic manifestations of hepatitis C virus chronic infection: Indications for a correct diagnosis. AB - Hepatitis C virus (HCV) is a hepato- and lymphotropic agent that is able to induce several autoimmune rheumatic disorders: vasculitis, sicca syndrome, arthralgias/arthritis and fibromyalgia. The severity of clinical manifestations is variable and sometimes life-threatening. HCV infection can mimic many primitive rheumatic diseases, therefore, it is mandatory to distinguish HCV related manifestations from primitive ones because the prognosis and therapeutic strategies can be fairly dissimilar. The new direct-acting antivirals drugs can help to avoid the well-known risks of worsening or new onset of autoimmune diseases during the traditional interferon-based therapies. PMID- 26819510 TI - Alcoholic liver disease and hepatitis C virus infection. AB - Alcohol consumption and hepatitis C virus (HCV) infection have a synergic hepatotoxic effect, and the coexistence of these factors increases the risk of advanced liver disease. The main mechanisms of this effect are increased viral replication and altered immune response, although genetic predisposition may also play an important role. Traditionally, HCV prevalence has been considered to be higher (up to 50%) in alcoholic patients than in the general population. However, the presence of advanced alcoholic liver disease (ALD) or intravenous drug use (IDU) may have confounded the results of previous studies, and the real prevalence of HCV infection in alcoholic patients without ALD or prior IDU has been shown to be lower. Due to the toxic combined effect of HCV and alcohol, patients with HCV infection should be screened for excessive ethanol intake. Patients starting treatment for HCV infection should be specifically advised to stop or reduce alcohol consumption because of its potential impact on treatment efficacy and adherence and may benefit from additional support during antiviral therapy. This recommendation might be extended to all currently recommended drugs for HCV treatment. Patients with alcohol dependence and HCV infection, can be treated with acamprosate, nalmefene, topiramate, and disulfiram, although baclofen is the only drug specifically tested for this purpose in patients with ALD and/or HCV infection. PMID- 26819511 TI - New approaches in the treatment of hepatitis C. AB - About 130-170 million people, is estimated to be infected with the hepatitis C virus (HCV). Chronic HCV infection is one of the leading causes of liver-related death and in many countries it is the primary reason for having a liver transplant. The main aim of antiviral treatment is to eradicate the virus. Until a few years ago the only treatment strategy was based on the combination of pegylated interferon and ribavirin (PEG/RBV). However, in genotypes 1 and 4 the rates of viral response did not surpass 50%, reaching up to 80% in the rest. In 2011 approval was given for the first direct acting antiviral agents (DAA), boceprevir and telaprevir, for treatment of genotype 1, in combination with traditional dual therapy. This strategy managed to increase the rates of sustained viral response (SVR) in both naive patients and in retreated patients, but with greater toxicity, interactions and cost, as well as being less safe in patients with advanced disease, in whom this treatment can trigger decompensation or even death. The recent, accelerated incorporation since 2013 of new more effective DAA, with pan-genomic properties and excellent tolerance, besides increasing the rates of SVR (even up to 100%), has also created a new scenario: shorter therapies, less toxicity and regimens free of PEG/RBV. This has enabled their almost generalised applicability in all patients. However, it should be noted that most of the scientific evidence available is based on expert opinion, case-control series, cohort studies and phase 2 and 3 trials, some with a reduced number of patients and select groups. Few data are currently available about the use of these drugs in daily clinical practice, particularly in relation to the appearance of side effects and interactions with other drugs, or their use in special populations or persons with the less common genotypes. This situation suggests the need for the generalised implementation of registries of patients receiving antiviral therapy. The main inconvenience of these new drugs is their high cost. This necessitates selection and prioritization of candidate patients to receive them, via strategies established by the various national organs, in accordance with the recommendations of scientific societies. PMID- 26819512 TI - Gut epithelial barrier dysfunction in human immunodeficiency virus-hepatitis C virus coinfected patients: Influence on innate and acquired immunity. AB - Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus (HIV)-infected patients have several non-acquired immunodeficiency syndrome (AIDS) related co morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus (HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed. PMID- 26819513 TI - Natural killer cells in hepatitis C: Current progress. AB - Patients infected with the hepatitis C virus (HCV) are characterized by a high incidence of chronic infection, which results in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The functional impairment of HCV specific T cells is associated with the evolution of an acute infection to chronic hepatitis. While T cells are the important effector cells in adaptive immunity, natural killer (NK) cells are the critical effector cells in innate immunity to virus infections. The findings of recent studies on NK cells in hepatitis C suggest that NK cell responses are indeed important in each phase of HCV infection. In the early phase, NK cells are involved in protective immunity to HCV. The immune evasion strategies used by HCV may target NK cells and might contribute to the progression to chronic hepatitis C. NK cells may control HCV replication and modulate hepatic fibrosis in the chronic phase. Further investigations are, however, needed, because a considerable number of studies observed functional impairment of NK cells in chronic HCV infection. Interestingly, the enhanced NK cell responses during interferon-alpha-based therapy of chronic hepatitis C indicate successful treatment. In spite of the advances in research on NK cells in hepatitis C, establishment of more physiological HCV infection model systems is needed to settle unsolved controversies over the role and functional status of NK cells in HCV infection. PMID- 26819514 TI - Metabolic alterations and hepatitis C: From bench to bedside. AB - In addition to causing cirrhosis and hepatocellular carcinoma, hepatitis C virus (HCV) is thought to cause hypolipidemia, hepatic steatosis, insulin resistance, metabolic syndrome, and diabetes. The viral life cycle of HCV depends on cholesterol metabolism in host cells. HCV core protein and nonstructural protein 5A perturb crucial lipid and glucose pathways, such as the sterol regulatory element-binding protein pathway and the protein kinase B/mammalian target of rapamycin/S6 kinase 1 pathway. Although several lines of transgenic mice expressing core or full HCV proteins exhibit hepatic steatosis and/or dyslipidemia, whether they completely reflect the metabolic alterations in humans with HCV infection remains unknown. Many cross-sectional studies have demonstrated increased prevalences of metabolic alterations and cardiovascular events in patients with chronic hepatitis C (CHC); however, conflicting results exist, primarily due to unavoidable individual variations. Utilizing anti-HCV therapy, most longitudinal cohort studies of CHC patients have demonstrated the favorable effects of viral clearance in attenuating metabolic alterations and cardiovascular risks. To determine the risks of HCV-associated metabolic alterations and associated complications in patients with CHC, it is necessary to adjust for crucial confounders, such as HCV genotype and host baseline glucose metabolism, for a long follow-up period after anti-HCV treatment. Adipose tissue is an important endocrine organ due to its release of adipocytokines, which regulate lipid and glucose metabolism. However, most data on HCV infection and adipocytokine alteration are inconclusive. A comprehensive overview of HCV associated metabolic and adipocytokine alterations, from bench to bedside, is presented in this topic highlight. PMID- 26819515 TI - Host restriction factors for hepatitis C virus. AB - Host-hepatitis C virus (HCV) interactions have both informed fundamental concepts of viral replication and pathogenesis and provided novel insights into host cell biology. These findings are illustrated by the recent discovery of host-encoded factors that restrict HCV infection. In this review, we briefly discuss these restriction factors in different steps of HCV infection. In each case, we discuss how these restriction factors were identified, the mechanisms by which they inhibit HCV infection and their potential contribution to viral pathogenesis. PMID- 26819516 TI - MicroRNA-mediated interactions between host and hepatitis C virus. AB - MicroRNAs (miRNAs) are small noncoding RNAs. More than 2500 mature miRNAs are detected in plants, animals and several types of viruses. Hepatitis C virus (HCV), which is a positive-sense, single-stranded RNA virus, does not encode viral miRNA. However, HCV infection alters the expression of host miRNAs, either in cell culture or in patients with liver disease progression, such as liver fibrosis, cirrhosis, and hepatocellular carcinoma. In turn, host miRNAs regulate HCV life cycle through directly binding to HCV RNAs or indirectly targeting cellular mRNAs. Increasing evidence demonstrates that miRNAs are one of the centered factors in the interaction network between virus and host. The competitive viral and host RNA hypothesis proposes a latent cross-regulation pattern between host mRNAs and HCV RNAs. High loads of HCV RNA sequester and de repress host miRNAs from their normal host targets and thus disturb host gene expression, indicating a means of adaptation for HCV to establish a persistent infection. Some special miRNAs are closely correlated with liver-specific disease progression and the changed levels of miRNAs are even higher sensitivity and specificity than those of traditional proteins. Therefore, some of them can serve as novel diagnostic/prognostic biomarkers in HCV-infected patients with liver diseases. They are also attractive therapeutic targets for development of new anti-HCV agents. PMID- 26819518 TI - Nutrition therapy: Integral part of liver transplant care. AB - Managing malnutrition before liver transplantation (LTx) while on the waiting list and, excessive weight gain/metabolic disturbances in post-surgery are still a challenge in LTx care. The aim of this review is to support an interdisciplinary nutrition approach of these patients. Cirrhotic patients are frequently malnourished before LTx and this is associated with a poor prognosis. Although the relation between nutritional status versus survival, successful operation and recovery after LTx is well established, prevalence of malnutrition before the operation is still very high. Emerging research has also demonstrated that sarcopenia pre and post-transplant is highly prevalent, despite the weight gain in the postoperative period. The diagnosis of the nutritional status is the first step to address the adequate nutritional therapy. Nutritional recommendations and therapy to manage the nutritional status of LTx patients are discussed in this review, regarding counseling on adequate diets and findings of the latest research on using certain immunonutrients in these patients (branched chain amino-acids, pre and probiotics). Nutrition associated complications observed after transplantation is also described. They are commonly related to the adverse effects of immunosuppressive drugs, leading to hyperkalemia, hyperglycemia and weight gain. Excessive weight gain and post-transplant metabolic disorders have long been described in post-LTx and should be addressed in order to reduce associated morbidity and mortality. PMID- 26819519 TI - Liver transplantation in acute liver failure: A challenging scenario. AB - Acute liver failure is a critical medical condition defined as rapid development of hepatic dysfunction associated with encephalopathy. The prognosis in these patients is highly variable and depends on the etiology, interval between jaundice and encephalopathy, age, and the degree of coagulopathy. Determining the prognosis for this population is vital. Unfortunately, prognostic models with both high sensitivity and specificity for prediction of death have not been developed. Liver transplantation has dramatically improved survival in patients with acute liver failure. Still, 25% to 45% of patients will survive with medical treatment. The identification of patients who will eventually require liver transplantation should be carefully addressed through the combination of current prognostic models and continuous medical assessment. The concerns of inaccurate selection for transplantation are significant, exposing the recipient to a complex surgery and lifelong immunosuppression. In this challenging scenario, where organ shortage remains one of the main problems, alternatives to conventional orthotopic liver transplantation, such as living-donor liver transplantation, auxiliary liver transplant, and ABO-incompatible grafts, should be explored. Although overall outcomes after liver transplantation for acute liver failure are improving, they are not yet comparable to elective transplantation. PMID- 26819520 TI - Different behaviour of BK-virus infection in liver transplant recipients. AB - Polyomavirus BK (BKV) infects up to 90% of the general population. After primary infection, occurring early during childhood, a state of non-replicative infection is established in the reno-urinary tract, without complications for immunocompetent hosts. In immunocompromised individuals, particularly transplanted patients, asymptomatic BKV viremia and/or viruria can be observed. Renal grafts may also be sources of infection as BKV prefers kidneys rather than other solid organs for transplantation such as the liver. The mechanism behind the higher incidence of BKV infection in kidney transplant patients, compared to liver or heart transplantation, is unclear and the prevalence of BKV infection in non-renal solid organ transplants has not been yet thoroughly investigated. We evaluated the prevalence of Polyomavirus BK infection among liver transplant recipients. A PubMed search was conducted using the terms BKV infection AND liver transplant recipients; BKV AND non-renal solid organ transplant*; BKV infection AND immunosuppression; the search was limited to title/abstract and English language articles published from 2000, to March 2015. Eleven relevant studies suggest that the prevalence of BKV viruria and/or viremia among liver transplant recipients is less than that reported in kidney or heart transplant recipients, except when chronic kidney disease (CKD) is present at the same time. Data also suggest that viruric and viremic patients have higher levels of serum creatinine than BKV negative patients. Moreover, no specific immunosuppressive drugs are associated with the onset of BKV nephropathy. The comorbidity of transplantation and CKD could play a major role in promoting BKV replication. PMID- 26819517 TI - Significance of hepatitis virus infection in the oncogenic initiation of hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) is a major risk factor in the development of the HCC, independently from excessive alcohol abuse and metabolic disease. Since the biology of HBV and HCV is different, their oncogenic effect may go through different mechanisms, direct and/or indirect. Viral hepatitis infection is associated with cellular inflammation, oxidative stress, and DNA damage, that may lead to subsequent hepatic injuries such as chronic hepatitis, fibrosis, cirrhosis, and finally HCC. Direct oncogenic properties of these viruses are related with their genotypic characteristics and the ability of viral proteins to interact with host proteins, thus altering the molecular pathways balance of the cells. In addition, the integration of HBV DNA, especially the gene S and X, in a particular site of the host genome can disrupt chromosomal stability and may activate various oncogenic mechanisms, including those in hematopoietic cells. Recently, several studies also had demonstrated that viral hepatitis could trigger the population of hepatic cancer stem cells. This review summarize available pre-clinical and clinical data in literature regarding oncogenic properties of HBV and HCV in the early initiation of HCC. PMID- 26819521 TI - Hemostasis in liver transplantation: Pathophysiology, monitoring, and treatment. AB - Recent findings in the pathophysiology and monitoring of hemostasis in patients with end stage liver disease have major impact on coagulation management during liver transplantation. There is increasing evidence, that the changes in both coagulation factors and platelet count regularly observed in patients with liver cirrhosis cannot be interpreted as a reliable indicator of diffuse bleeding risk. Instead, a differentiated view on hemostasis has led to the concept of a rebalanced coagulation system: While it is important to recognize that procoagulant factors are reduced in liver cirrhosis, it is also evident that synthesis of anticoagulant factors and fibrinolytic proteins produced in the liver is also diminished. Similarly, the decreased platelet count may be counterbalanced by increased platelet aggregability caused by highly active von Willebrand multimeres. The coagulation system is therefor stated to be rebalanced. While under normal "unstressed" conditions diffuse bleeding is rarely observed, however both diffuse bleeding or thrombus formation may occur when compensation mechanisms are exhausted. While most patients presenting for liver transplantation have severe cirrhosis, liver function and thus production of pro- and anticoagulant factors can be preserved especially in cholestatic liver disease. During liver transplantation, profound changes in the hemostasis system can occur. Surgical bleeding can lead to diffuse bleeding as coagulation factors and platelets are already reduced. Ischemia and tissue trauma can lead to alterations of hemostasis comparable to trauma induced coagulopathy. A further common disturbance often starting with the reperfusion of the transplanted organ is hyperfibrinolysis which can eventually precipitate complete consumption of fibrinogen and an endogenous heparinization by glycocalyx shedding. Moreover, thrombotic events in liver transplantations are not uncommon and contribute to increased mortality. Besides conventional laboratory methods, bed-side monitoring of hemostasis (e.g., thrombelastography, thrombelastometry) is often used during liver transplantation to rapidly diagnose decreases in fibrinogen and platelet count as well as hyperfibrinolysis and to guide treatment with blood products, factor concentrates, and antifibrinolytics. There is also evidence which suggests when algorithms based on bed-side hemostasis monitoring are used a reduction of blood loss, blood product use, and eventual mortality are possible. Notably, the bed-side monitoring of anticoagulant pathways and the thrombotic risk is not possible at time and thus a cautious and restrictive use of blood products is recommended. PMID- 26819522 TI - Post reperfusion syndrome during liver transplantation: From pathophysiology to therapy and preventive strategies. AB - This review aims at evaluating the existing evidence regarding post reperfusion syndrome, providing a description of the pathophysiologic mechanisms involved and possible management and preventive strategies. A PubMed search was conducted using the MeSH database, "Reperfusion" AND "liver transplantation" were the combined MeSH headings; EMBASE and the Cochrane library were also searched using the same terms. 52 relevant studies and one ongoing trial were found. The concept of post reperfusion syndrome has evolved through years to a multisystemic disorder. The implications of the main organ, recipient and procedure related factors in the genesis of this complex syndrome are discussed in the text as the novel pharmacologic and technical approaches to reduce its incidence. However the available evidence about risk factors, physiopathology and preventive measures is still confusing, the presence of two main definitions and the numerosity of possible confounding factors greatly complicates the interpretation of the studies. PMID- 26819524 TI - Modulation of splanchnic circulation: Role in perioperative management of liver transplant patients. AB - Splanchnic circulation is the primary mechanism that regulates volumes of circulating blood and systemic blood pressure in patients with cirrhosis accompanied by portal hypertension. Recently, interest has been expressed in modulating splanchnic circulation in patients with liver cirrhosis, because this capability might produce beneficial effects in cirrhotic patients undergoing a liver transplant. Pharmacologic modulation of splanchnic circulation by use of vasoconstrictors might minimize venous congestion, replenish central blood flow, and thus optimize management of blood volume during a liver transplant operation. Moreover, splanchnic modulation minimizes any high portal blood flow that may occur following liver resection and the subsequent liver transplant. This effect is significant, because high portal flow impairs liver regeneration, and thus adversely affects the postoperative recovery of a transplant patient. An increase in portal blood flow can be minimized by either surgical methods (e.g., splenic artery ligation, splenectomy or portocaval shunting) or administration of splanchnic vasoconstrictor drugs such as Vasopressin or terlipressin. Finally, modulation of splanchnic circulation can help maintain perioperative renal function. Splanchnic vasoconstrictors such as terlipressin may help protect against acute kidney injury in patients undergoing liver transplantation by reducing portal pressure and the severity of a hyperdynamic state. These effects are especially important in patients who receive a too small for size graft. Terlipressin selectively stimulates V1 receptors, and thus causes arteriolar vasoconstriction in the splanchnic region, with a consequent shift of blood from splanchnic to systemic circulation. As a result, terlipressin enhances renal perfusion by increasing both effective blood volume and mean arterial pressure. PMID- 26819523 TI - Liver transplantation for viral hepatitis in 2015. AB - Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release. PMID- 26819525 TI - Current diagnosis and treatment of benign biliary strictures after living donor liver transplantation. AB - Despite advances in surgical techniques, benign biliary strictures after living donor liver transplantation (LDLT) remain a significant biliary complication and play an important role in graft and patient survival. Benign biliary strictures after transplantation are classified into anastomotic or non-anastomotic strictures. These two types differ in presentation, outcome, and response to therapy. The leading causes of biliary strictures include impaired blood supply, technical errors during surgery, and biliary anomalies. Because patients usually have non-specific symptoms, a high index of suspicion should be maintained. Magnetic resonance cholangiography has gained widespread acceptance as a reliable noninvasive tool for detecting biliary complications. Endoscopy has played an increasingly prominent role in the diagnosis and treatment of biliary strictures after LDLT. Endoscopic management in LDLT recipients may be more challenging than in deceased donor liver transplantation patients because of the complex nature of the duct-to-duct reconstruction. Repeated aggressive endoscopic treatment with dilation and the placement of multiple plastic stents is considered the first line treatment for biliary strictures. Percutaneous and surgical treatments are now reserved for patients for whom endoscopic management fails and for those with multiple, inaccessible intrahepatic strictures or Roux-en-Y anastomoses. Recent advances in enteroscopy enable treatment, even in these latter cases. Direct cholangioscopy, another advanced form of endoscopy, allows direct visualization of the inner wall of the biliary tree and is expected to facilitate stenting or stone extraction. Rendezvous techniques can be a good option when the endoscopic approach to the biliary stricture is unfeasible. These developments have resulted in almost all patients being managed by the endoscopic approach. PMID- 26819526 TI - Application of contrast-enhanced ultrasound after liver transplantation: Current status and perspectives. AB - Liver transplantation is an effective treatment for patients with end-stage liver disease. Accurate imaging evaluation of the transplanted patient is critical for ensuring that the limited donor liver is functioning appropriately. Ultrasound contrast agents (UCAs), in combination with contrast-specific imaging techniques, are increasingly accepted in clinical use for the assessment of the hepatic vasculature, bile ducts and liver parenchyma in pre-, intra- and post-transplant patients. We describe UCAs, their technical requirements, the recommended clinical indications, image interpretation and the limitations for contrast enhanced ultrasound applications in liver transplantation. PMID- 26819527 TI - Vascular complications after adult living donor liver transplantation: Evaluation with ultrasonography. AB - Living donor liver transplantation (LDLT) has been widely used to treat end-stage liver disease with improvement in surgical technology and the application of new immunosuppressants. Vascular complications after liver transplantation remain a major threat to the survival of recipients. LDLT recipients are more likely to develop vascular complications because of their complex vascular reconstruction and the slender vessels. Early diagnosis and treatment are critical for the survival of graft and recipients. As a non-invasive, cost-effective and non radioactive method with bedside availability, conventional gray-scale and Doppler ultrasonography play important roles in identifying vascular complications in the early postoperative period and during the follow-up. Recently, with the detailed vascular tracing and perfusion visualization, contrast-enhanced ultrasound (CEUS) has significantly improved the diagnosis of postoperative vascular complications. This review focuses on the role of conventional gray-scale ultrasound, Doppler ultrasound and CEUS for early diagnosis of vascular complications after adult LDLT. PMID- 26819529 TI - Diagnosing gastrointestinal illnesses using fecal headspace volatile organic compounds. AB - Volatile organic compounds (VOCs) emitted from stool are the components of the smell of stool representing the end products of microbial activity and metabolism that can be used to diagnose disease. Despite the abundance of hydrogen, carbon dioxide, and methane that have already been identified in human flatus, the small portion of trace gases making up the VOCs emitted from stool include organic acids, alcohols, esters, heterocyclic compounds, aldehydes, ketones, and alkanes, among others. These are the gases that vary among individuals in sickness and in health, in dietary changes, and in gut microbial activity. Electronic nose devices are analytical and pattern recognition platforms that can utilize mass spectrometry or electrochemical sensors to detect these VOCs in gas samples. When paired with machine-learning and pattern recognition algorithms, this can identify patterns of VOCs, and thus patterns of smell, that can be used to identify disease states. In this review, we provide a clinical background of VOC identification, electronic nose development, and review gastroenterology applications toward diagnosing disease by the volatile headspace analysis of stool. PMID- 26819528 TI - Impact of obesity treatment on gastroesophageal reflux disease. AB - Gastroesophageal reflux disease (GERD) is a frequently encountered disorder. Obesity is an important risk factor for GERD, and there are several pathophysiologic mechanisms linking the two conditions. For obese patients with GERD, much of the treatment effort is focused on weight loss and its consistent benefit to symptoms, while there is a relative lack of evidence regarding outcomes after novel or even standard medical therapy is offered to this population. Physicians are hesitant to recommend operative anti-reflux therapy to obese patients due to the potentially higher risks and decreased efficacy, and these patients instead are often considered for bariatric surgery. Bariatric surgical approaches are broadening, and each technique has emerging evidence regarding its effect on both the risk and outcome of GERD. Furthermore, combined anti-reflux and bariatric options are now being offered to obese patients with GERD. However, currently Roux-en-Y gastric bypass remains the most effective surgical treatment option in this population, due to its consistent benefits in both weight loss and GERD itself. This article aims to review the impact of both conservative and aggressive approaches of obesity treatment on GERD. PMID- 26819530 TI - Hepatitis C in non-hepatic solid organ transplant candidates and recipients: A new horizon. AB - Hepatitis C virus (HCV) infection is estimated to affect 130-150 million people globally which corresponds to 2%-3% of the total world population. It remains the leading indication for liver transplant worldwide and has been demonstrated to negatively impact both patient and graft survival following non-hepatic organ transplantation. In the era of interferon-based therapy, although treatment and cure of HCV prior to non-hepatic transplant improved survival, tolerability and low cure rates substantially limited therapy. Interferon (IFN)-based therapy following non-hepatic solid organ transplant, due to the risk of allograft rejection, is generally contraindicated. Rapid advances in IFN-free therapy with direct acting antivirals (DAAs) in the last few years have completely changed the paradigm of hepatitis C therapy. Compared to IFN-based regimens, DAAs have less frequent and less severe adverse effects, shorter durations of therapy, and higher cure rates that are minimally impacted by historically negative predictors of response such as cirrhosis, ethnicity, and post-transplant state. Recent studies have shown that liver transplant (LT) recipients can be safely and effectively treated with DAA combination therapies; although data are limited, many of the principles of therapy in LT may be extrapolated to non-hepatic solid organ transplant recipients. Here we review the data on DAA combination therapies in transplantation, discuss the advantages and disadvantages of pre- vs post transplant HCV therapy and future directions. PMID- 26819531 TI - Mechanisms of intrahepatic triglyceride accumulation. AB - Hepatic steatosis defined as lipid accumulation in hepatocytes is very frequently found in adults and obese adolescents in the Western World. Etiologically, obesity and associated insulin resistance or excess alcohol intake are the most frequent causes of hepatic steatosis. However, steatosis also often occurs with chronic hepatitis C virus (HCV) infection and is also found in rare but potentially life-threatening liver diseases of pregnancy. Clinical significance and outcome of hepatic triglyceride accumulation are highly dependent on etiology and histological pattern of steatosis. This review summarizes current concepts of pathophysiology of common causes of hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease, chronic HCV infections, drug-induced forms of hepatic steatosis, and acute fatty liver of pregnancy. Regarding the pathophysiology of NAFLD, this work focuses on the close correlation between insulin resistance and hepatic triglyceride accumulation, highlighting the potential harmful effects of systemic insulin resistance on hepatic metabolism of fatty acids on the one side and the role of lipid intermediates on insulin signalling on the other side. Current studies on lipid droplet morphogenesis have identified novel candidate proteins and enzymes in NAFLD. PMID- 26819532 TI - Diagnosis of follicular lymphoma of the gastrointestinal tract: A better initial diagnostic workup. AB - Due to an increasing incidence and more frequent recognition by endoscopists, gastrointestinal follicular lymphoma has been established as a variant of follicular lymphoma. However, due to its rarity, there are no established guidelines on the optimal diagnostic strategy for patients with primary gastrointestinal follicular lymphoma or secondary gastrointestinal involvement of systemic follicular lymphoma. This review offers an overview and pitfalls to avoid during the initial diagnostic workup of this disease entity. Previously reported case reports, case series, and retrospective studies are reviewed and focus on the disease's endoscopic and histological features, the roles of computed tomography and positron emission tomography scanning, the clinical utility of the soluble interleukin-2 receptor, and the possible pathogenesis. PMID- 26819534 TI - Appraisal of needle-based confocal laser endomicroscopy in the diagnosis of pancreatic cysts. AB - Nearly 2.5% of cross-sectional imaging studies will report a finding of a cystic pancreatic lesion. Even though most of these are incidental findings, it remains very concerning for both patients and treating clinicians. Differentiating and predicting malignant transformation in pancreatic cystic lesions is clinically challenging. Current evaluation of suspicious cystic lesions includes a combination of radiologic imaging, endoscopic ultrasound (EUS) and cyst fluid analyses. Despite these attempts, precise diagnostic stratification among non mucinous, mucinous, and malignant cystic lesions is often not possible until surgical resection. EUS-guided needle based confocal laser endomicroscopy (nCLE) for evaluation of pancreatic cysts is emerging as a powerful technique with remarkable potential. Though limited imaging data from 3 large clinical trials (INSPECT, DETECT and CONTACT) are currently the reference standard for nCLE imaging, nonetheless these have not been validated in large studies. The aim of this review article is to review the evolving role of EUS-guided nCLE in management of pancreatic cystic lesions in terms of its significance, adverse events, limitations, and implications. PMID- 26819533 TI - Hepatitis C virus prevalence and genotype distribution in Pakistan: Comprehensive review of recent data. AB - Hepatitis C virus (HCV) is endemic in Pakistan and its burden is expected to increase in coming decades owing mainly to widespread use of unsafe medical procedures. The prevalence of HCV in Pakistan has previously been reviewed. However, the literature search conducted here revealed that at least 86 relevant studies have been produced since the publication of these systematic reviews. A revised updated analysis was therefore needed in order to integrate the fresh data. A systematic review of data published between 2010 and 2015 showed that HCV seroprevalence among the general adult Pakistani population is 6.8%, while active HCV infection was found in approximately 6% of the population. Studies included in this review have also shown extremely high HCV prevalence in rural and underdeveloped peri-urban areas (up to 25%), highlighting the need for an increased focus on this previously neglected socioeconomic stratum of the population. While a 2.45% seroprevalence among blood donors demands immediate measures to curtail the risk of transfusion transmitted HCV, a very high prevalence in patients attending hospitals with various non-liver disease related complaints (up to 30%) suggests a rise in the incidence of nosocomial HCV spread. HCV genotype 3a continues to be the most prevalent subtype infecting people in Pakistan (61.3%). However, recent years have witnessed an increase in the frequency of subtype 2a in certain geographical sub-regions within Pakistan. In Khyber Pakhtunkhwa and Sindh provinces, 2a was the second most prevalent genotype (17.3% and 11.3% respectively). While the changing frequency distribution of various genotypes demands an increased emphasis on research for novel therapeutic regimens, evidence of high nosocomial transmission calls for immediate measures aimed at ensuring safe medical practices. PMID- 26819536 TI - Systematic review of prognostic importance of extramural venous invasion in rectal cancer. AB - AIM: To systematically review the survival outcomes relating to extramural venous invasion in rectal cancer. METHODS: A systematic review was conducted using PRISMA guidelines. An electronic search was carried out using MEDLINE, EMBASE, CINAHL, Cochrane library databases, Google scholar and PubMed until October 2014. Search terms were used in combination to yield articles on extramural venous invasion in rectal cancer. Outcome measures included prevalence and 5-year survival rates. These were graphically displayed using Forest plots. Statistical analysis of the data was carried out. RESULTS: Fourteen studies reported the prevalence of extramural venous invasion (EMVI) positive patients. Prevalence ranged from 9%-61%. The pooled prevalence of EMVI positivity was 26% [Random effects: Event rate 0.26 (0.18, 0.36)]. Most studies showed that EMVI related to worse oncological outcomes. The pooled overall survival was 39.5% [Random effects: Event rate 0.395 (0.29, 0.51)]. CONCLUSION: Historically, there has been huge variation in the prevalence of EMVI through inconsistent reporting. However the presence of EMVI clearly leads to worse survival outcomes. As detection rates become more consistent, EMVI may be considered as part of risk-stratification in rectal cancer. Standardised histopathological definitions and the use of magnetic resonance imaging to identify EMVI will improve detection rates in the future. PMID- 26819537 TI - Treatment of chronic hepatitis B patients with tyrosine-methionine-aspartate aspartate mutations. AB - Lamivudine is an antiviral used for the treatment of chronic hepatitis B. Several studies have reported various mutations that are induced by lamivudine therapy. These mutations in the tyrosine-methionine-aspartate-aspartate (YMDD) motif are necessary and sufficient to confer high-level lamivudine resistance. During treatment with lamivudine, mutations develop in the YMDD motif of the hepatitis B virus (HBV) polymerase gene and lamivudine cannot prevent the replication of the mutant form. The virulence strain of developed mutation in the polymerase gene is lower than the original virus and they are susceptible to treatment with some other nucleoside analogs except lamivudine. Entecavir and tenofovir are potent HBV inhibitors and they can be confidently used as first line monotherapies. We read the article written by Tan et al that lamivudine therapy improved the clinical course in HBV patients with natural YMDD mutations. We think that lamivudine use for this patient group is not appropriate. These patients should use YMDD mutant form-effective drugs such as adefovir, tenofovir. PMID- 26819539 TI - On the importance of edaphic variables to predict plant species distributions - limits and prospects. AB - Although the importance of edaphic parameters on plant growth and survival is known, they are rarely incorporated as predictors in plant' species distribution models (SDM). Dubuis et al., in this issue, show they may improve the performance of plant SDMs in Alpine ecosystems. It paves the way for more comprehensive assessments of the values of including edaphic variables into SDMs. PMID- 26819535 TI - Non-invasive assessment of liver fibrosis: Between prediction/prevention of outcomes and cost-effectiveness. AB - The assessment of the fibrotic evolution of chronic hepatitis has always been a challenge for the clinical hepatologist. Over the past decade, various non invasive methods have been proposed to detect the presence of fibrosis, including the elastometric measure of stiffness, panels of clinical and biochemical parameters, and combinations of both methods. The aim of this review is to analyse the most recent data on non-invasive techniques for the evaluation of hepatic fibrosis with particular attention to cost-effectiveness. We searched for relevant studies published in English using the PubMed database from 2009 to the present. A large number of studies have suggested that elastography and serum markers are useful techniques for diagnosing severe fibrosis and cirrhosis and for excluding significant fibrosis in hepatitis C virus patients. In addition, hepatic stiffness may also help to prognosticate treatment response to antiviral therapy. It has also been shown that magnetic resonance elastography has a high accuracy for staging and differentiating liver fibrosis. Finally, studies have shown that non-invasive methods are becoming increasingly precise in either positively identifying or excluding liver fibrosis, thus reducing the need for liver biopsy. However, both serum markers and transient elastography still have "grey area" values of lower accuracy. In this case, liver biopsy is still required to properly assess liver fibrosis. Recently, the guidelines produced by the World Health Organization have suggested that the AST-to-platelet ratio index or FIB-4 test could be utilised for the evaluation of liver fibrosis rather than other, more expensive non-invasive tests, such as elastography or FibroTest. PMID- 26819540 TI - Discovering All Transcriptome Single-Nucleotide Polymorphisms and Scanning for Selection Signatures in Ducks (Anas platyrhynchos). AB - The duck is one of the most economically important waterfowl as a source of meat, eggs, and feathers. Characterizing the genetic variation in duck species is an important step toward linking genes or genomic regions with phenotypes. Human driven selection during duck domestication and subsequent breed formation has likely left detectable signatures in duck genome. In this study, we employed a panel of >1.4 million single-nucleotide polymorphisms (SNPs) identified from the RNA sequencing (RNA-seq) data of 15 duck individuals. The density of the resulting SNPs is significantly positively correlated with the density of genes across the duck genome, which demonstrates that the usage of the RNA-seq data allowed us to enrich variant functional categories, such as coding exons, untranslated regions (UTRs), introns, and downstream/upstream. We performed a complete scan of selection signatures in the ducks using the composite likelihood ratio (CLR) and found 76 candidate regions of selection, many of which harbor genes related to phenotypes relevant to the function of the digestive system and fat metabolism, including TCF7L2, EIF2AK3, ELOVL2, and fatty acid-binding protein family. This study illustrates the potential of population genetic approaches for identifying genomic regions affecting domestication-related phenotypes and further helps to increase the known genetic information about this economically important animal. PMID- 26819541 TI - Phylotranscriptomic Analysis Based on Coalescence was Less Influenced by the Evolving Rates and the Number of Genes: A Case Study in Ericales. AB - Advances in high-throughput sequencing have generated a vast amount of transcriptomic data that are being increasingly used in phylogenetic reconstruction. However, processing the vast datasets for a huge number of genes and even identifying optimal analytical methodology are challenging. Through de novo sequenced and retrieved data from public databases, we identified 221 orthologous protein-coding genes to reconstruct the phylogeny of Ericales, an order characterized by rapid ancient radiation. Seven species representing different families in Ericales were used as in-groups. Both concatenation and coalescence methods yielded the same well-supported topology as previous studies, with only two nodes conflicting with previously reported relationships. The results revealed that a partitioning strategy could improve the traditional concatenation methodology. Rapidly evolving genes negatively affected the concatenation analysis, while slowly evolving genes slightly affected the coalescence analysis. The coalescence methods usually accommodated rate heterogeneity better and required fewer genes to yield well-supported topologies than the concatenation methods with both real and simulated data. PMID- 26819542 TI - Gene Tree Affects Inference of Sites Under Selection by the Branch-Site Test of Positive Selection. AB - The branch-site test of positive selection is a standard approach to detect past episodic positive selection in a priori-specified branches of a gene phylogeny. Here, we ask if differences in the topology of the gene tree have any influence on the ability to infer positively selected sites. Using simulated sequences, we compare the results obtained for true and rearranged topologies. We find a strong relationship between "conflicting branch length," which occurs when the set of sequences that experiences selection for a given topology and foreground is changed, and the ability to predict positively selected sites. Moreover, by reanalyzing a previously published data set, we show that the choice of a gene tree also affects the results obtained for real-world sequences. This is the first study to demonstrate that tree topology has a clear effect on the inference of positive selection. We conclude that the choice of a gene tree is an important factor for the branch-site analysis of positive selection. PMID- 26819543 TI - A Polyglot Approach to Bioinformatics Data Integration: A Phylogenetic Analysis of HIV-1. AB - As sequencing technologies continue to drop in price and increase in throughput, new challenges emerge for the management and accessibility of genomic sequence data. We have developed a pipeline for facilitating the storage, retrieval, and subsequent analysis of molecular data, integrating both sequence and metadata. Taking a polyglot approach involving multiple languages, libraries, and persistence mechanisms, sequence data can be aggregated from publicly available and local repositories. Data are exposed in the form of a RESTful web service, formatted for easy querying, and retrieved for downstream analyses. As a proof of concept, we have developed a resource for annotated HIV-1 sequences. Phylogenetic analyses were conducted for >6,000 HIV-1 sequences revealing spatial and temporal factors influence the evolution of the individual genes uniquely. Nevertheless, signatures of origin can be extrapolated even despite increased globalization. The approach developed here can easily be customized for any species of interest. PMID- 26819544 TI - Structural Diversity of a Novel LTR Retrotransposon, RTPOSON, in the Genus Oryza. AB - Retrotransposons with long terminal repeats (LTRs) are the most abundant transposable elements in plant genomes. A novel LTR retrotransposon named RTPOSON primarily occurs in the genus Oryza and in several species of the Poaceae family. RTPOSON has been identified in the Ty1-copia group of retrotransposons because two of its open reading frames encode an uncharacterized protein and UBN2_2 and zinc knuckle, respectively. More than 700 RTPOSONs were identified in Oryza genomes; 127 RTPOSONs with LTRs and gag-pol elements were classified into three subgroups. The subgroup RTPOSON_sub3 had the smallest DNA size and 97% (32/33) of RTPOSON elements from Oryza punctata are classified in this group. The insertion time of these RTPOSONs varied and their proliferation occurred within the last 8 Mya, with two bursting periods within the last 1.5-5.0 Mya. A total of 37 different orthologous insertions of RTPOSONs, with different nested transposable elements and gene fragments, were identified by comparing the genomes of ssp. japonica cv. Nipponbare and ssp. indica cv. 93-11. A part of intact RTPOSON elements was evolved independently after the divergence of indica and japonica. In addition, intact RTPOSONs and homologous fragments were preferentially retained or integrated in genic regions. This novel LTR retrotransposon, RTPOSON, might have an impact on genome evolution, genic innovation, and genetic variation. PMID- 26819545 TI - Correlation between Gene Variants, Signaling Pathways, and Efficacy of Chemotherapy Drugs against Colon Cancers. AB - Efficacies, toxicities, and resistance mechanisms of chemotherapy drugs, such as oxaliplatin and 5-fluorouracil (5-FU), vary widely among various categories and subcategories of colon cancers. By understanding the differences in the drug efficacy and resistance at the level of protein-protein networks, we identified the correlation between the drug activity of oxaliplatin/5-FU and gene variations from the US National Cancer Institute-60 human cancer cell lines. The activity of either of these drugs is correlated with specific amino acid variant(s) of KRAS and other genes from the signaling pathways of colon cancer progression. We also discovered that the activity of a non-DNA-binding novel platinum drug, phosphaplatin, is comparable with oxaliplatin and 5-FU when it was tested against colon cancer cell lines. Our strategy that combines the knowledge from pharmacogenomics across cell lines with the molecular information from specific cancer cells is beneficial for predicting the outcome of a possible combination therapy for personalized treatment. PMID- 26819547 TI - Bioinformatics Resources for MicroRNA Discovery. AB - Biomarker identification is often associated with the diagnosis and evaluation of various diseases. Recently, the role of microRNA (miRNA) has been implicated in the development of diseases, particularly cancer. With the advent of next generation sequencing, the amount of data on miRNA has increased tremendously in the last decade, requiring new bioinformatics approaches for processing and storing new information. New strategies have been developed in mining these sequencing datasets to allow better understanding toward the actions of miRNAs. As a result, many databases have also been established to disseminate these findings. This review focuses on several curated databases of miRNAs and their targets from both predicted and validated sources. PMID- 26819548 TI - Electrochemical Behavior and Voltammetric Determination of a Manganese(II) Complex at a Carbon Paste Electrode. AB - Investigation of the electrochemical behavior using cyclic voltammetry and detection of [Mn(2+)(thiophenyl-2-carboxylic acid)2 (triethanolamine)] with adsorptive stripping differential pulse voltammetry. The electrochemical behavior of a manganese(II) complex [Mn(2+)(thiophenyl-2-carboxylic acid)2(triethanolamine)] (A) was investigated using cyclic and differential pulse voltammetry in an acetate buffer of pH 4.6 at a carbon paste electrode. Further, an oxidation-reduction mechanism was proposed. Meanwhile, an adsorptive stripping differential pulse voltammetric method was developed for the determination of manganese(II) complex. PMID- 26819550 TI - Transcriptomic Sequencing Reveals a Set of Unique Genes Activated by Butyrate Induced Histone Modification. AB - Butyrate is a nutritional element with strong epigenetic regulatory activity as a histone deacetylase inhibitor. Based on the analysis of differentially expressed genes in the bovine epithelial cells using RNA sequencing technology, a set of unique genes that are activated only after butyrate treatment were revealed. A complementary bioinformatics analysis of the functional category, pathway, and integrated network, using Ingenuity Pathways Analysis, indicated that these genes activated by butyrate treatment are related to major cellular functions, including cell morphological changes, cell cycle arrest, and apoptosis. Our results offered insight into the butyrate-induced transcriptomic changes and will accelerate our discerning of the molecular fundamentals of epigenomic regulation. PMID- 26819549 TI - Interfering with Bacterial Quorum Sensing. AB - Quorum sensing (QS) describes the exchange of chemical signals in bacterial populations to adjust the bacterial phenotypes according to the density of bacterial cells. This serves to express phenotypes that are advantageous for the group and ensure bacterial survival. To do so, bacterial cells synthesize autoinducer (AI) molecules, release them to the environment, and take them up. Thereby, the AI concentration reflects the cell density. When the AI concentration exceeds a critical threshold in the cells, the AI may activate the expression of virulence-associated genes or of luminescent proteins. It has been argued that targeting the QS system puts less selective pressure on these pathogens and should avoid the development of resistant bacteria. Therefore, the molecular components of QS systems have been suggested as promising targets for developing new anti-infective compounds. Here, we review the QS systems of selected gram-negative and gram-positive bacteria, namely, Vibrio fischeri, Pseudomonas aeruginosa, and Staphylococcus aureus, and discuss various antivirulence strategies based on blocking different components of the QS machinery. PMID- 26819552 TI - Evolutionary Character of Alternative Splicing in Plants. AB - Alternative splicing (AS) is one of the most important ways to enhance the functional diversity of genes. Huge amounts of data have been produced by microarray, expressed sequence tag, and RNA-seq, and plenty of methods have been developed specifically for this task. The most frequently asked questions in previous research were as follows. What is the content rate of AS genes among the whole gene set? How many AS types are presented in the genome, and which type is dominant? How about the conservation ability of AS among different species? Which kinds of isoforms from some genes have the environmental response to help individual adaptation? Based on this background, we collected analysis results from 17 species to try to map out the landscape of AS studies in plants. We have noted the shortages of previous results, and we appeal to all scientists working in the AS field to make a standard protocol so that analyses between different projects are comparable. PMID- 26819551 TI - Biochemical Analysis of Genome Functions Using Locus-Specific Chromatin Immunoprecipitation Technologies. AB - To isolate specific genomic regions that retain their molecular interactions, allowing direct identification of chromatin-bound molecules, we developed two locus-specific chromatin immunoprecipitation (locus-specific ChIP) technologies, insertional ChIP (iChIP) and engineered DNA-binding molecule-mediated ChIP (enChIP) using the clustered regularly interspaced short palindromic repeats (CRISPR) system or transcription activator-like (TAL) proteins. Essentially, a locus-specific ChIP consists of locus-tagging and affinity purification and can be combined with downstream analyses to identify molecules associated with the target genomic regions. In this review, we discuss the applications of locus specific ChIP to analyze the genome functions, including transcription and epigenetic regulation. PMID- 26819553 TI - Reciprocal Effects of Internalizing and Oppositional Defiance Symptoms on Heavy Drinking and Alcohol-Related Harms in Young Adulthood. AB - There is a need for longitudinal research to understand how psychopathology relates to the onset and maintenance of substance use from adolescence into young adulthood. Hence, we investigate the longitudinal, reciprocal influences of internalizing (anxiety and depression) and externalizing (oppositional defiance) symptoms on heavy episodic drinking (HED; >=5 drinks per occasion) and alcohol related harms in a community-based sample of youth aged 12-27 years. Participants were chosen from the Victoria Healthy Youth Survey, followed six times, biennially between 2003 and 2013 (N = 662). Analyses used cross-lagged panel models to examine reciprocal relations over time. Differences across age and sex were also tested. Defiance symptoms predicted increases in HED, which reciprocally predicted increases in defiance symptoms for females. Internalizing symptoms were related to HED within time for females. Alcohol-related harms had reciprocal positive associations with internalizing and defiance symptoms for both males and females. Associations were largely invariant across age groups, suggesting that the presence and strength of associations persisted across development. While psychopathology preceded the onset of HED and harms, the overall findings suggest that these risk processes are mutually reinforcing across development and that youth may become entrenched in an interdependent cycle that significantly increases their risk of comorbid disorders in adulthood. PMID- 26819554 TI - Keeping Mind in Mind: Mentalizing and Executive Functioning in Substance-Abusing Infant Mothers: Effect on Dyadic Relationship and Infant Outcome. AB - Although it is well documented that maternal substance abuse has a negative effect on the mother-child interaction, less is known about the pathways through which the interaction is compromised. The main objective of this research proposal is to describe an ongoing research project that focuses on associations between maternal executive function and the quality of mother-infant interaction when the mother has a history of substance abuse. We will also investigate the effects of multiple variables, including maternal relationship experiences, personality disposition, parental stress, comorbid mental illness, and addiction severity, on the dyadic interaction and child functioning. A group of 40-50 mothers with substance abuse problems and their infants aged 6-18 months will be included. The mothers will be assessed with neuropsychological tests, clinical interviews, self-administered questionnaires, and dyadic interaction observations as well as observation and assessment of child functioning. We will use a cross sectional correlational design. The inclusion of the participants will end in October 2015. Further knowledge about the variables that are important for the mother-infant relationship can inform future research and clinical practice. PMID- 26819555 TI - How Well Do Survey Studies Capture Alcohol's Harm to Others? AB - Empirical studies assessing alcohol's harm to others very often rely on population survey data. This study addresses some of the problems and challenges in using survey data for this purpose. Such problems include the limited capacity of population surveys in identifying infrequent harm and long-term consequences of drinking. Moreover, the drinker may report the alcohol-related harm or the person being harmed may report the damage. However, irrespective of who reports the harm, causal attribution to drinking is problematic. Challenges for future population surveys to address alcohol's harm to others include the need for improved models and understanding of complex mechanisms to guide empirical studies within the broad range of harm. Study designs other than cross-sectional surveys, such as longitudinal study designs and combinations of population surveys and other data sources, are likely to overcome some of the identified problems in current population surveys of alcohol's harm to others. PMID- 26819556 TI - Air Pollutant Mapping with a Mobile Laboratory During the BEE-TEX Field Study. AB - The Aerodyne Mobile Laboratory was deployed to the Houston Ship Channel and surrounding areas during the Benzene and Other Toxics Exposure field study in February 2015. We evaluated atmospheric concentrations of volatile organic hydrocarbons and other hazardous air pollutants of importance to human health, including benzene, 1,3-butadiene, toluene, xylenes, ethylbenzenes, styrene, and NO2. Ambient concentration measurements were focused on the neighborhoods of Manchester, Harrisburg, and Galena Park. The most likely measured concentration of 1,3-butadiene in the Manchester neighborhood (0.17 ppb) exceeds the Environmental Protection Agency's E-5 lifetime cancer risk level of 0.14 ppb. In all the three neighborhoods, the measured benzene concentration falls below or within the E-5 lifetime cancer risk levels of 0.4-1.4 ppb for benzene. Pollution maps as a function of wind direction show the impact of nearby sources. PMID- 26819557 TI - Rapid Point-of-Care Isothermal Amplification Assay for the Detection of Malaria without Nucleic Acid Purification. AB - Malaria remains one of the most prevalent infectious diseases and results in significant mortality. Isothermal amplification (loop-mediated isothermal amplification) is used to detect malarial DNA at levels of ~1 parasite/uL blood in <=30 minutes without the isolation of parasite nucleic acid from subject's blood or saliva. The technique targets the mitochondrial cytochrome oxidase subunit 1 gene and is capable of distinguishing Plasmodium falciparum from Plasmodium vivax. Malarial diagnosis by the gold standard microscopic examination of blood smears is generally carried out only after moderate-to-severe symptoms appear. Rapid diagnostic antigen tests are available but generally require infection levels in the range of 200-2,000 parasites/uL for a positive diagnosis and cannot distinguish if the disease has been cleared due to the persistence of circulating antigen. This study describes a rapid and simple molecular assay to detect malarial genes directly from whole blood or saliva without DNA isolation. PMID- 26819559 TI - Biofilm Cohesive Strength as a Basis for Biofilm Recalcitrance: Are Bacterial Biofilms Overdesigned? AB - Bacterial biofilms are highly resistant to common antibacterial treatments, and several physiological explanations have been offered to explain the recalcitrant nature of bacterial biofilms. Herein, a biophysical aspect of biofilm recalcitrance is being reported on. While engineering structures are often overdesigned with a factor of safety (FOS) usually under 10, experimental measurements of biofilm cohesive strength suggest that the FOS is on the order of thousands. In other words, bacterial biofilms appear to be designed to withstand extreme forces rather than typical or average loads. In scenarios requiring the removal or control of unwanted biofilms, this emphasizes the importance of considering strategies for structurally weakening the biofilms in conjunction with bacterial inactivation. PMID- 26819546 TI - MicroRNAs Expressed during Viral Infection: Biomarker Potential and Therapeutic Considerations. AB - MicroRNAs (miRNAs) are short sequences of noncoding single-stranded RNAs that exhibit inhibitory effects on complementary target mRNAs. Recently, it has been discovered that certain viruses express their own miRNAs, while other viruses activate the transcription of cellular miRNAs for their own benefit. This review summarizes the viral and/or cellular miRNAs that are transcribed during infection, with a focus on the biomarker and therapeutic potential of miRNAs (or their antagomirs). Several human viruses of clinical importance are discussed, namely, herpesviruses, polyomaviruses, hepatitis B virus, hepatitis C virus, human papillomavirus, and human immunodeficiency virus. PMID- 26819560 TI - Single-Nucleotide Mutations in FMR1 Reveal Novel Functions and Regulatory Mechanisms of the Fragile X Syndrome Protein FMRP. AB - Fragile X syndrome is a monogenic disorder and a common cause of intellectual disability. Despite nearly 25 years of research on FMR1, the gene underlying the syndrome, very few pathological mutations other than the typical CGG-repeat expansion have been reported. This is in contrast to other X-linked, monogenic, intellectual disability disorders, such as Rett syndrome, where many point mutations have been validated as causative of the disorder. As technology has improved and significantly driven down the cost of sequencing, allowing for whole genes to be sequenced with relative ease, in-depth sequencing studies on FMR1 have recently been performed. These studies have led to the identification of novel variants in FMR1, where some of which have been functionally evaluated and are likely pathogenic. In this review, we discuss recently identified FMR1 variants, the ways these novel variants cause dysfunction, and how they reveal new regulatory mechanisms and functionalities of the gene. PMID- 26819558 TI - Lipid Acyl Chain Remodeling in Yeast. AB - Membrane lipid homeostasis is maintained by de novo synthesis, intracellular transport, remodeling, and degradation of lipid molecules. Glycerophospholipids, the most abundant structural component of eukaryotic membranes, are subject to acyl chain remodeling, which is defined as the post-synthetic process in which one or both acyl chains are exchanged. Here, we review studies addressing acyl chain remodeling of membrane glycerophospholipids in Saccharomyces cerevisiae, a model organism that has been successfully used to investigate lipid synthesis and its regulation. Experimental evidence for the occurrence of phospholipid acyl chain exchange in cardiolipin, phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine is summarized, including methods and tools that have been used for detecting remodeling. Progress in the identification of the enzymes involved is reported, and putative functions of acyl chain remodeling in yeast are discussed. PMID- 26819562 TI - Mechanisms Involved in Toxicity of Liver Caused by Piroxicam in Mice and Protective Effects of Leaf Extract of Hibiscus rosa-sinensis L. AB - Piroxicam is one of the important therapeutic nonsteroidal anti-inflammatory class of drugs used mainly to suppress pain and inflammation in arthritis and other musculoskeletal disorders. Besides being anti-inflammatory, these drugs are analgesic and antipyretic often used for the relief of nonspecific fever condition. Recently, piroxicam has also gained attention as an effective therapy for tumors, colorectal, and invasive bladder cancers. The objective of the current study is to evaluate the protective effects of the alcoholic leaf extract of Hibiscus rosa-sinensis (AEH), Malvaceae, against piroxicam-induced toxicity in mice. Sixty adult Swiss albino mice (Mus musculus) were divided into four groups (n = 10), which included a control group, a group treated orally with AEH (30 mg kg(-1) b.w.) for 15 days, a group treated orally with piroxicam (6.6 mg kg(-1) b.w.) for 15 days, and another group treated orally with piroxicam and AEH for 15 days. The results indicated that treatment with piroxicam alone resulted in a significant increase in the activities of serum marker enzymes, namely, aspartate transaminase, alanine transaminase, and alkaline phosphatase with profound hepatic lipid peroxidation as evidenced by a marked increment in the level of thoibarbituric acid reactive substances along with a distinct diminution in reduced glutathoine content and various antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase in the liver. However, treatment with AEH during piroxicam treatment retrieved or partially antagonized the effects induced by piroxicam toward the normal values of controls. Histopathological observations also corroborate with the above findings. It can be concluded that AEH exhibited a protective action against piroxicam toxicity and effective in combating oxidative stress-induced hepatic damage. PMID- 26819561 TI - Clinical Features of Neuropsychiatric Syndromes in Systemic Lupus Erythematosus and Other Connective Tissue Diseases. AB - Systemic lupus erythematosus (SLE) and related disorders are chronic inflammatory diseases characterized by abnormalities and, in some cases, even complete failure of immune responses as the underlying pathology. Although almost all connective tissue diseases and related disorders can be complicated by various neuropsychiatric syndromes, SLE is a typical connective tissue disease that can cause neurological and psychiatric syndromes. In this review, neuropsychiatric syndromes complicating connective tissue diseases, especially SLE are outlined, and pathological and other conditions that should be considered in the differential diagnosis are also discussed. PMID- 26819564 TI - "Pinstripe Pattern" in an Achalasia Patient. AB - Endoscopic image of achalasia usually shows dilated esophageal cavity with retained liquids and foods. Recently, "pinstripe pattern" (PSP) in the case of achalasia patient was reported as an endoscopic image of the indicator for early detection of achalasia. The typical endoscopic image of PSP can be recognized in this case. PMID- 26819565 TI - A Case Report: A Third/Fourth Branchial Pouch Anomaly Presented by Solid Thyroid and Lateral Cervical Neck Masses. AB - Branchial pouch-derived anomalies may arise from remnants of the first, second, or third/fourth branchial arches. Branchial pouch-related structures are found within the thyroid gland in the form of solid cell rests, epithelial lined cyst with or without an associated lymphoid component, thymic and/or parathyroid tissue, and less commonly in the form of heterotopic cartilage. We present a rare case of left solid thyroid swelling nearby two cervical nodules in a seven-year old female with a clinical diagnosis suggestive of malignant thyroid tumor with metastasis to the cervical lymph nodes. Histopathological examination revealed that it was compatible with third/fourth branchial pouch-derived anomaly composed of mature cartilage and thymic and parathyroid tissues for clinical and radiological correlations. PMID- 26819563 TI - Recent Treatments of Interstitial Lung Disease with Systemic Sclerosis. AB - Systemic sclerosis (SSc) is a disorder characterized by immune dysfunction, microvascular injury, and fibrosis. Organ involvement in patients with SSc is variable; however, pulmonary involvement occurs in up to 90% of patients with SSc. Interstitial lung disease (ILD) is a major cause of mortality and, thus, a major determinant in the prognosis of patients with SSc. This review summarizes current findings about the characteristics of ILD in patients with SSc, selection of patients with SSc-ILD who are candidates for the treatment, and current treatment options. PMID- 26819566 TI - Retinal Targets ALDH Positive Cancer Stem Cell and Alters the Phenotype of Highly Metastatic Osteosarcoma Cells. AB - Aldehyde dehydrogenase (ALDH) is a cancer stem cell marker. Retinoic acid has antitumor properties, including the induction of apoptosis and inhibition of proliferation. Retinal, the precursor of retinoic acid, can be oxidized to retinoic acid by dehydrogenases, including ALDH. We hypothesized that retinal could potentially be transformed to retinoic acid with higher efficiency by cancer stem cells, due to the higher ALDH activity. We previously observed that ALDH activity is greater in highly metastatic K7M2 osteosarcoma (OS) cells than in nonmetastatic K12 OS cells. We also demonstrated that ALDH activity correlates with clinical metastases in bone sarcoma patients, suggesting that ALDH may be a therapeutic target specific to cells with high metastatic potential. Our current results demonstrated that retinal preferentially affected the phenotypes of ALDH high K7M2 cells in contrast to ALDH-low K12 cells, which could be mediated by the more efficient transformation of retinal to retinoic acid by ALDH in K7M2 cells. Retinal treatment of highly metastatic K7M2 cells decreased their proliferation, invasion capacity, and resistance to oxidative stress. Retinal altered the expression of metastasis-related genes. These observations indicate that retinal may be used to specifically target metastatic cancer stem cells in OS. PMID- 26819567 TI - Intra-Articular Synovial Sarcomas: Incidence and Differentiating Features from Localized Pigmented Villonodular Synovitis. AB - Purpose. To determine the incidence of intra-articular synovial sarcomas and investigate if any radiological variables can differentiate them from localized (unifocal) pigmented villonodular synovitis (PVNS) and if multivariate data analysis could be used as a complementary clinical tool. Methods. Magnetic resonance images and radiographs of 7 cases of intra-articular synovial sarcomas and 14 cases of localized PVNS were blindedly reviewed. Variables analyzed were size, extra-articular growth, tumor border, blooming, calcification, contrast media enhancement, effusion, bowl of grapes sign, triple signal intensity sign, synovial low signal intensity, synovitis, age, and gender. Univariate and multivariate data analysis, the method of partial least squares-discriminant analysis (PLS-DA), were used. Register data on all synovial sarcomas were extracted for comparison. Results. The incidence of intra-articular synovial sarcomas was 3%. PLS-DA showed that age, effusion, size, and gender were the most important factors for discrimination between sarcomas and localized PVNS. No sarcomas were misclassified as PVNS with PLS-DA, while some PVNS were misclassified as sarcomas. Conclusions. The most important variables in differentiating intra-articular sarcomas from localized PVNS were age, effusion, size, and gender. Multivariate data analysis can be helpful as additive information to avoid a biopsy, if the tumor is classified as most likely being PVNS. PMID- 26819568 TI - Residential Mobility in Early Childhood: Household and Neighborhood Characteristics of Movers and Non-Movers. AB - BACKGROUND: Understanding residential mobility in early childhood is important for contextualizing influences on child health and well-being. OBJECTIVE: This study describes individual, household, and neighborhood characteristics associated with residential mobility for children aged 0-5. METHODS: We examined longitudinal data from the Early Childhood Longitudinal Study-Birth Cohort (ECLS B), a nationally representative sample of children born in 2001. Frequencies describe the prevalence of characteristics for four waves of data and adjusted Wald tests compared means. RESULTS: Moving was common for these families with young children, as nearly three-quarters of children moved at least once. Movers transitioned to neighborhoods with residents of higher socioeconomic status but experienced no improved household socioeconomic position relative to non-movers. CONCLUSION: Both the high prevalence and unique implications of early childhood residential mobility suggest the need for further research. PMID- 26819569 TI - Sequence, Structure, and Binding Analysis of Cyclodextrinase (TK1770) from T. kodakarensis (KOD1) Using an In Silico Approach. AB - Thermostable cyclodextrinase (Tk1770 CDase) from hyperthermophilic archaeon Thermococcus kodakarensis (KOD1) hydrolyzes cyclodextrins into linear dextrins. The sequence of Tk1770 CDase retrieved from UniProt was aligned with sequences of sixteen CD hydrolyzing enzymes and a phylogenetic tree was constructed using Bayesian inference. The homology model of Tk1770 CDase was constructed and optimized with Modeller v9.14 program. The model was validated with ProSA server and PROCHECK analysis. Four conserved regions and the catalytic triad consisting of Asp411, Glu437, and Asp502 of GH13 family were identified in catalytic site. Also an additional fifth conserved region downstream to the fourth region was also identified. The structure of Tk1770 CDase consists of an additional N' domain and a helix-loop-helix motif that is conserved in all archaeal CD hydrolyzing enzymes. The N'-domain contains an extended loop region that forms a part of catalytic domain and plays an important role in stability and substrate binding. The docking of substrate into catalytic site revealed the interactions with different conserved residues involved in substrate binding and formation of enzyme-substrate complex. PMID- 26819570 TI - Growth, inter- and intraspecific variation, palaeobiogeography, taphonomy and systematics of the Cenozoic ghost shrimp Glypturus. AB - Studies in systematic palaeontology are greatly aided when numerous, well preserved specimens are available so that quantitative methods can be used to substantiate qualitative observations. This is often not the case for fossil decapod crustaceans due to their relatively low preservation potential. Here, we examined primarily two large collections of the well-preserved ghost shrimp Glypturus from the Holo-Pleistocene of Panama and the late Miocene of Florida. Using descriptive, bivariate, multivariate and geometric morphometric methods, two new species are described based on appendage material: Glypturus panamacanalensis sp. nov. and G. sikesi sp. nov. New characters are identified, and size-related and intraspecific variation are assessed for these taxa and modern G. acanthochirus. Taxonomic placement of single specimens from other localities was confirmed by multivariate methods. Furthermore, Glypturus is revised, especially with regard to Western Atlantic species that inhabited both carbonate and siliciclastic environments. Callianassa anguillensis, C. latidigata, and Neocallichirus? quisquellanus are referred to as Glypturus sp. until more material is available to determine the validity of these species. Diversity within Glypturus may thus be underestimated, thereby also impacting the assessment of phylogenetic relationships. Minor propodi appear under-represented relative to major propodi, suggesting a taphonomic bias. Single specimens of interest include a specimen of G. panamacanalensis sp. nov. exhibiting a peculiar swelling in the fixed finger and another showing damage on the propodal upper margin, suggesting failed predation or antagonistic behaviour. Glypturus is first found in the Oligocene in the Western Atlantic and may have expanded its palaeobiogeographical range since the Miocene. The genus was still present on the Pacific side of the Isthmus of Panama in the Holo-Pleistocene, but is only known from the Western Atlantic today, suggesting a relatively recent extinction on the Pacific side. PMID- 26819571 TI - Economic evaluations of interventions to reduce neonatal morbidity and mortality: a review of the evidence in LMICs and its implications for South Africa. AB - BACKGROUND: Newborn mortality, comprising a third of all under-5 deaths, has hardly changed in low and middle income countries (LMICs) including South Africa over the past decade. To attain the MDG 4 target, greater emphasis must be placed on wide-scale implementation of proven, cost-effective interventions. This paper reviews economic evidence on effective neonatal health interventions in LMICs from 2000-2013; documents lessons for South African policy on neonatal health; and identifies gaps and areas for future research. METHODS: A narrative review was performed in leading public health databases for full economic evaluations conducted between 2000 and 2013. Data extraction from the articles included in the review was guided by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist, and the quality of the included economic evaluations was assessed using the Quality of Health Economics Studies Instrument (QHES). RESULTS: Twenty-seven economic evaluations were identified, from South East Asia and sub-Saharan Africa, with those from sub-Saharan Africa primarily focused on HIV/AIDS. Packages of care to prevent neonatal mortality were more cost-effective than vertical interventions. A wide variability in methodological approaches challenges the comparability of study results between countries. In South Africa, there is limited cost-effectiveness evidence for the interventions proposed by the National Perinatal Morbidity and Mortality Committee. CONCLUSIONS: Neonatal strategies have a strong health system focus but this review suggests that strengthening community care could be an additional component for averting neonatal deaths. While some evidence exists, having a more complete understanding of how to most effectively deploy scarce resources for neonatal health in South Africa in the post-2015 era is essential. PMID- 26819572 TI - R package MVR for Joint Adaptive Mean-Variance Regularization and Variance Stabilization. AB - We present an implementation in the R language for statistical computing of our recent non-parametric joint adaptive mean-variance regularization and variance stabilization procedure. The method is specifically suited for handling difficult problems posed by high-dimensional multivariate datasets (p ? n paradigm), such as in 'omics'-type data, among which are that the variance is often a function of the mean, variable-specific estimators of variances are not reliable, and tests statistics have low powers due to a lack of degrees of freedom. The implementation offers a complete set of features including: (i) normalization and/or variance stabilization function, (ii) computation of mean-variance regularized t and F statistics, (iii) generation of diverse diagnostic plots, (iv) synthetic and real 'omics' test datasets, (v) computationally efficient implementation, using C interfacing, and an option for parallel computing, (vi) manual and documentation on how to setup a cluster. To make each feature as user friendly as possible, only one subroutine per functionality is to be handled by the end-user. It is available as an R package, called MVR ('Mean-Variance Regularization'), downloadable from the CRAN. PMID- 26819574 TI - Widely Tunable Morphologies in Block Copolymer Thin Films Through Solvent Vapor Annealing Using Mixtures of Selective Solvents. AB - Thin films of block copolymers are extremely attractive for nanofabrication because of their ability to form uniform and periodic nanoscale structures by microphase separation. One shortcoming of this approach is that to date the design of a desired equilibrium structure requires synthesis of a block copolymer de novo within the corresponding volume ratio of the blocks. In this work, we investigated solvent vapor annealing in supported thin films of poly(2 hydroxyethyl methacrylate)-block-poly(methyl methacrylate) [PHEMA-b-PMMA] by means of grazing incidence small angle X-ray scattering (GISAXS). A spin-coated thin film of lamellar block copolymer was solvent vapor annealed to induce microphase separation and improve the long-range order of the self-assembled pattern. Annealing in a mixture of solvent vapors using a controlled volume ratio of solvents (methanol, MeOH, and tetrahydrofuran, THF), which are chosen to be preferential for each block, enabled selective formation of ordered lamellae, gyroid, hexagonal or spherical morphologies from a single block copolymer with a fixed volume fraction. The selected microstructure was then kinetically trapped in the dry film by rapid drying. To our knowledge, this paper describes the first reported case where in-situ methods are used to study the transition of block copolymer films from one initial disordered morphology to four different ordered morphologies, covering much of the theoretical diblock copolymer phase diagram. PMID- 26819573 TI - Acculturation, hazardous drinking and depressive symptomatology among Hispanics enrolled in a clinical trial. AB - BACKGROUND: Among Hispanics in the U.S., lower acculturation level has been found to be protective against alcohol abuse and depression. However, this relationship may not hold within at-risk samples. The prevalence and co-occurrence of hazardous drinking and depressive symptoms and their relationship to acculturation were examined among Hispanics enrolled in a study to reduce heavy drinking. At enrollment, all participants reported past-month heavy drinking (one or more occasions of >4/5 drinks for females/males, and average weekly consumption >7/14 drinks per week). We explored whether gender moderated the effects of acculturation on hazardous drinking and depressive symptoms. METHODS: Participants (N = 100) completed measures at baseline. RESULTS: Eighty-nine percent of participants met criteria for hazardous alcohol use as assessed by the AUDIT and of those, 55% (n=49) also reported elevated depressive symptoms. Of those who reported elevated depressive symptoms, nearly all (94%) met AUDIT criteria for hazardous drinking. Acculturation was not related to hazardous drinking or depressive symptoms in the full sample. Highly acculturated women reported more hazardous drinking than less acculturated women. Acculturation was not associated with hazardous drinking in men, but less acculturated men reported higher levels of depression than highly acculturated men. DISCUSSION: Depression should be assessed in alcohol interventions for Hispanics. Alcohol interventions should be tailored for acculturation level and gender to improve relevance and efficacy. Clinical Trial Registration #NCT01996280. PMID- 26819575 TI - Anti-leptospirosis agglutinins in Brazilian capybaras (hydrochoerus hydrochaeris). AB - BACKGROUND: The interest in commercial use of wild animals is increasing, especially regarding raising of capybaras. Although this wild species is potentially lucrative for the production of meat, oil and leather, it is suggested as a probable reservoir of leptospires. METHODS: Due to the economic importance of this species and the lack of studies concerning leptospirosis, the presence of anti-leptospirosis agglutinins was assayed in 55 serum samples of capybaras (Hydrochoerus hydrochaeris) from commercial and experimental breeding flocks located in Sao Paulo state, Parana state, and Rio Grande do Sul state, Brazil. Samples were obtained through cephalic or femoral venipunction (5 to 10 mL). Microscopic agglutination test was used according to the Brazilian Health Ministry considering as cut-off titer of 100. RESULTS: Out of the 55 samples analyzed, 23 (41.82 %) tested positive. The most prevalent serovar was Icterohaemorrhagiae (56.52 %) in 13 samples, followed by Copenhageni in nine samples (39.13 %), Pomona in four samples (17.39 %), Djasiman and Castellonis in three samples each (13.04 %), Grippotyphosa, Hardjo, Canicola, and Cynopteri in two samples each (8.7 %), and Andamana and Bratislava in one sample each (4.34 %). CONCLUSIONS: These results suggest the evidence of exposure to Leptospira spp. and the need of new studies to evaluate a higher number of capybaras from different regions to better understand the importance of leptospirosis infection in these animals and verify the zoonotic role of this species as a possible source of infection to humans and other animals. PMID- 26819577 TI - Using Genetic Programming with Prior Formula Knowledge to Solve Symbolic Regression Problem. AB - A researcher can infer mathematical expressions of functions quickly by using his professional knowledge (called Prior Knowledge). But the results he finds may be biased and restricted to his research field due to limitation of his knowledge. In contrast, Genetic Programming method can discover fitted mathematical expressions from the huge search space through running evolutionary algorithms. And its results can be generalized to accommodate different fields of knowledge. However, since GP has to search a huge space, its speed of finding the results is rather slow. Therefore, in this paper, a framework of connection between Prior Formula Knowledge and GP (PFK-GP) is proposed to reduce the space of GP searching. The PFK is built based on the Deep Belief Network (DBN) which can identify candidate formulas that are consistent with the features of experimental data. By using these candidate formulas as the seed of a randomly generated population, PFK-GP finds the right formulas quickly by exploring the search space of data features. We have compared PFK-GP with Pareto GP on regression of eight benchmark problems. The experimental results confirm that the PFK-GP can reduce the search space and obtain the significant improvement in the quality of SR. PMID- 26819576 TI - Smad2/3 Upregulates the Expression of Vimentin and Affects Its Distribution in DBP-Exposed Sertoli Cells. AB - Sertoli cells (SCs) in the testes provide physical and nutritional support to germ cells. The vimentin cytoskeleton in SCs is disrupted by dibutyl phthalate (DBP), which leads to SCs dysfunction. In a previous study, we found that peroxisome proliferator-activated receptor alpha (PPARalpha) influenced the distribution of vimentin by affecting its phosphorylation in DBP-exposed SCs. In the present study, we investigated the role of Smad2/3 in regulating the expression of vimentin in DBP-exposed SCs. We hypothesized that Smad2/3 affects the distribution of vimentin by regulating its expression and that there is cross talk between Smad2/3 and PPARalpha. The real-time PCR and ChIP-qPCR results showed that SB431542 (an inhibitor of Smad2/3) could significantly attenuate the expression of vimentin induced by DBP in SCs. Phosphorylated and soluble vimentin were both downregulated by SB431542 pretreatment. WY14643 (an agonist of PPARalpha) pretreatment stimulated, while GW6471 (an antagonist of PPARalpha) inhibited, the activity of Smad2/3; SB431542 pretreatment also inhibited the activity of PPARalpha, but it did not rescue the DBP-induced collapse in vimentin. Our results suggest that, in addition to promoting the phosphorylation of vimentin, DBP also stimulates the expression of vimentin by activating Smad2/3 in SCs and thereby induces irregular vimentin distribution. PMID- 26819578 TI - Evaluation of Second-Level Inference in fMRI Analysis. AB - We investigate the impact of decisions in the second-level (i.e., over subjects) inferential process in functional magnetic resonance imaging on (1) the balance between false positives and false negatives and on (2) the data-analytical stability, both proxies for the reproducibility of results. Second-level analysis based on a mass univariate approach typically consists of 3 phases. First, one proceeds via a general linear model for a test image that consists of pooled information from different subjects. We evaluate models that take into account first-level (within-subjects) variability and models that do not take into account this variability. Second, one proceeds via inference based on parametrical assumptions or via permutation-based inference. Third, we evaluate 3 commonly used procedures to address the multiple testing problem: familywise error rate correction, False Discovery Rate (FDR) correction, and a two-step procedure with minimal cluster size. Based on a simulation study and real data we find that the two-step procedure with minimal cluster size results in most stable results, followed by the familywise error rate correction. The FDR results in most variable results, for both permutation-based inference and parametrical inference. Modeling the subject-specific variability yields a better balance between false positives and false negatives when using parametric inference. PMID- 26819579 TI - Using Self-Organizing Neural Network Map Combined with Ward's Clustering Algorithm for Visualization of Students' Cognitive Structural Models about Aliveness Concept. AB - We propose an approach to clustering and visualization of students' cognitive structural models. We use the self-organizing map (SOM) combined with Ward's clustering to conduct cluster analysis. In the study carried out on 100 subjects, a conceptual understanding test consisting of open-ended questions was used as a data collection tool. The results of analyses indicated that students constructed the aliveness concept by associating it predominantly with human. Motion appeared as the most frequently associated term with the aliveness concept. The results suggest that the aliveness concept has been constructed using anthropocentric and animistic cognitive structures. In the next step, we used the data obtained from the conceptual understanding test for training the SOM. Consequently, we propose a visualization method about cognitive structure of the aliveness concept. PMID- 26819580 TI - Classifying EEG Signals during Stereoscopic Visualization to Estimate Visual Comfort. AB - With stereoscopic displays a sensation of depth that is too strong could impede visual comfort and may result in fatigue or pain. We used Electroencephalography (EEG) to develop a novel brain-computer interface that monitors users' states in order to reduce visual strain. We present the first system that discriminates comfortable conditions from uncomfortable ones during stereoscopic vision using EEG. In particular, we show that either changes in event-related potentials' (ERPs) amplitudes or changes in EEG oscillations power following stereoscopic objects presentation can be used to estimate visual comfort. Our system reacts within 1 s to depth variations, achieving 63% accuracy on average (up to 76%) and 74% on average when 7 consecutive variations are measured (up to 93%). Performances are stable (~62.5%) when a simplified signal processing is used to simulate online analyses or when the number of EEG channels is lessened. This study could lead to adaptive systems that automatically suit stereoscopic displays to users and viewing conditions. For example, it could be possible to match the stereoscopic effect with users' state by modifying the overlap of left and right images according to the classifier output. PMID- 26819581 TI - Pose-Invariant Face Recognition via RGB-D Images. AB - Three-dimensional (3D) face models can intrinsically handle large pose face recognition problem. In this paper, we propose a novel pose-invariant face recognition method via RGB-D images. By employing depth, our method is able to handle self-occlusion and deformation, both of which are challenging problems in two-dimensional (2D) face recognition. Texture images in the gallery can be rendered to the same view as the probe via depth. Meanwhile, depth is also used for similarity measure via frontalization and symmetric filling. Finally, both texture and depth contribute to the final identity estimation. Experiments on Bosphorus, CurtinFaces, Eurecom, and Kiwi databases demonstrate that the additional depth information has improved the performance of face recognition with large pose variations and under even more challenging conditions. PMID- 26819582 TI - Bioinspired Intelligent Algorithm and Its Applications for Mobile Robot Control: A Survey. AB - Bioinspired intelligent algorithm (BIA) is a kind of intelligent computing method, which is with a more lifelike biological working mechanism than other types. BIAs have made significant progress in both understanding of the neuroscience and biological systems and applying to various fields. Mobile robot control is one of the main application fields of BIAs which has attracted more and more attention, because mobile robots can be used widely and general artificial intelligent algorithms meet a development bottleneck in this field, such as complex computing and the dependence on high-precision sensors. This paper presents a survey of recent research in BIAs, which focuses on the research in the realization of various BIAs based on different working mechanisms and the applications for mobile robot control, to help in understanding BIAs comprehensively and clearly. The survey has four primary parts: a classification of BIAs from the biomimetic mechanism, a summary of several typical BIAs from different levels, an overview of current applications of BIAs in mobile robot control, and a description of some possible future directions for research. PMID- 26819583 TI - A Generalized National Planning Approach for Admission Capacity in Higher Education: A Nonlinear Integer Goal Programming Model with a Novel Differential Evolution Algorithm. AB - This paper proposes a nonlinear integer goal programming model (NIGPM) for solving the general problem of admission capacity planning in a country as a whole. The work aims to satisfy most of the required key objectives of a country related to the enrollment problem for higher education. The system general outlines are developed along with the solution methodology for application to the time horizon in a given plan. The up-to-date data for Saudi Arabia is used as a case study and a novel evolutionary algorithm based on modified differential evolution (DE) algorithm is used to solve the complexity of the NIGPM generated for different goal priorities. The experimental results presented in this paper show their effectiveness in solving the admission capacity for higher education in terms of final solution quality and robustness. PMID- 26819584 TI - Adaptive Grouping Cloud Model Shuffled Frog Leaping Algorithm for Solving Continuous Optimization Problems. AB - The shuffled frog leaping algorithm (SFLA) easily falls into local optimum when it solves multioptimum function optimization problem, which impacts the accuracy and convergence speed. Therefore this paper presents grouped SFLA for solving continuous optimization problems combined with the excellent characteristics of cloud model transformation between qualitative and quantitative research. The algorithm divides the definition domain into several groups and gives each group a set of frogs. Frogs of each region search in their memeplex, and in the search process the algorithm uses the "elite strategy" to update the location information of existing elite frogs through cloud model algorithm. This method narrows the searching space and it can effectively improve the situation of a local optimum; thus convergence speed and accuracy can be significantly improved. The results of computer simulation confirm this conclusion. PMID- 26819585 TI - A Biogeography-Based Optimization Algorithm Hybridized with Tabu Search for the Quadratic Assignment Problem. AB - The quadratic assignment problem (QAP) is an NP-hard combinatorial optimization problem with a wide variety of applications. Biogeography-based optimization (BBO), a relatively new optimization technique based on the biogeography concept, uses the idea of migration strategy of species to derive algorithm for solving optimization problems. It has been shown that BBO provides performance on a par with other optimization methods. A classical BBO algorithm employs the mutation operator as its diversification strategy. However, this process will often ruin the quality of solutions in QAP. In this paper, we propose a hybrid technique to overcome the weakness of classical BBO algorithm to solve QAP, by replacing the mutation operator with a tabu search procedure. Our experiments using the benchmark instances from QAPLIB show that the proposed hybrid method is able to find good solutions for them within reasonable computational times. Out of 61 benchmark instances tested, the proposed method is able to obtain the best known solutions for 57 of them. PMID- 26819586 TI - Neural Networks Technique for Filling Gaps in Satellite Measurements: Application to Ocean Color Observations. AB - A neural network (NN) technique to fill gaps in satellite data is introduced, linking satellite-derived fields of interest with other satellites and in situ physical observations. Satellite-derived "ocean color" (OC) data are used in this study because OC variability is primarily driven by biological processes related and correlated in complex, nonlinear relationships with the physical processes of the upper ocean. Specifically, ocean color chlorophyll-a fields from NOAA's operational Visible Imaging Infrared Radiometer Suite (VIIRS) are used, as well as NOAA and NASA ocean surface and upper-ocean observations employed--signatures of upper-ocean dynamics. An NN transfer function is trained, using global data for two years (2012 and 2013), and tested on independent data for 2014. To reduce the impact of noise in the data and to calculate a stable NN Jacobian for sensitivity studies, an ensemble of NNs with different weights is constructed and compared with a single NN. The impact of the NN training period on the NN's generalization ability is evaluated. The NN technique provides an accurate and computationally cheap method for filling in gaps in satellite ocean color observation fields and time series. PMID- 26819587 TI - Prediction of Soil Deformation in Tunnelling Using Artificial Neural Networks. AB - In the past few decades, as a new tool for analysis of the tough geotechnical problems, artificial neural networks (ANNs) have been successfully applied to address a number of engineering problems, including deformation due to tunnelling in various types of rock mass. Unlike the classical regression methods in which a certain form for the approximation function must be presumed, ANNs do not require the complex constitutive models. Additionally, it is traced that the ANN prediction system is one of the most effective ways to predict the rock mass deformation. Furthermore, it could be envisaged that ANNs would be more feasible for the dynamic prediction of displacements in tunnelling in the future, especially if ANN models are combined with other research methods. In this paper, we summarized the state-of-the-art and future research challenges of ANNs on the tunnel deformation prediction. And the application cases as well as the improvement of ANN models were also presented. The presented ANN models can serve as a benchmark for effective prediction of the tunnel deformation with characters of nonlinearity, high parallelism, fault tolerance, learning, and generalization capability. PMID- 26819588 TI - Nonparametric Facial Feature Localization Using Segment-Based Eigenfeatures. AB - We present a nonparametric facial feature localization method using relative directional information between regularly sampled image segments and facial feature points. Instead of using any iterative parameter optimization technique or search algorithm, our method finds the location of facial feature points by using a weighted concentration of the directional vectors originating from the image segments pointing to the expected facial feature positions. Each directional vector is calculated by linear combination of eigendirectional vectors which are obtained by a principal component analysis of training facial segments in feature space of histogram of oriented gradient (HOG). Our method finds facial feature points very fast and accurately, since it utilizes statistical reasoning from all the training data without need to extract local patterns at the estimated positions of facial features, any iterative parameter optimization algorithm, and any search algorithm. In addition, we can reduce the storage size for the trained model by controlling the energy preserving level of HOG pattern space. PMID- 26819589 TI - Generalization Bounds Derived IPM-Based Regularization for Domain Adaptation. AB - Domain adaptation has received much attention as a major form of transfer learning. One issue that should be considered in domain adaptation is the gap between source domain and target domain. In order to improve the generalization ability of domain adaption methods, we proposed a framework for domain adaptation combining source and target data, with a new regularizer which takes generalization bounds into account. This regularization term considers integral probability metric (IPM) as the distance between the source domain and the target domain and thus can bound up the testing error of an existing predictor from the formula. Since the computation of IPM only involves two distributions, this generalization term is independent with specific classifiers. With popular learning models, the empirical risk minimization is expressed as a general convex optimization problem and thus can be solved effectively by existing tools. Empirical studies on synthetic data for regression and real-world data for classification show the effectiveness of this method. PMID- 26819590 TI - Real-Time Monitoring and Fault Diagnosis of a Low Power Hub Motor Using Feedforward Neural Network. AB - Low power hub motors are widely used in electromechanical systems such as electrical bicycles and solar vehicles due to their robustness and compact structure. Such systems driven by hub motors (in wheel motors) encounter previously defined and undefined faults under operation. It may inevitably lead to the interruption of the electromechanical system operation; hence, economic losses take place at certain times. Therefore, in order to maintain system operation sustainability, the motor should be precisely monitored and the faults are diagnosed considering various significant motor parameters. In this study, the artificial feedforward backpropagation neural network approach is proposed to real-time monitor and diagnose the faults of the hub motor by measuring seven main system parameters. So as to construct a necessary model, we trained the model, using a data set consisting of 4160 samples where each has 7 parameters, by the MATLAB environment until the best model is obtained. The results are encouraging and meaningful for the specific motor and the developed model may be applicable to other types of hub motors. The prosperous model of the whole system was embedded into Arduino Due microcontroller card and the mobile real-time monitoring and fault diagnosis system prototype for hub motor was designed and manufactured. PMID- 26819591 TI - An Enhanced Artificial Bee Colony Algorithm with Solution Acceptance Rule and Probabilistic Multisearch. AB - The artificial bee colony (ABC) algorithm is a popular swarm based technique, which is inspired from the intelligent foraging behavior of honeybee swarms. This paper proposes a new variant of ABC algorithm, namely, enhanced ABC with solution acceptance rule and probabilistic multisearch (ABC-SA) to address global optimization problems. A new solution acceptance rule is proposed where, instead of greedy selection between old solution and new candidate solution, worse candidate solutions have a probability to be accepted. Additionally, the acceptance probability of worse candidates is nonlinearly decreased throughout the search process adaptively. Moreover, in order to improve the performance of the ABC and balance the intensification and diversification, a probabilistic multisearch strategy is presented. Three different search equations with distinctive characters are employed using predetermined search probabilities. By implementing a new solution acceptance rule and a probabilistic multisearch approach, the intensification and diversification performance of the ABC algorithm is improved. The proposed algorithm has been tested on well-known benchmark functions of varying dimensions by comparing against novel ABC variants, as well as several recent state-of-the-art algorithms. Computational results show that the proposed ABC-SA outperforms other ABC variants and is superior to state-of-the-art algorithms proposed in the literature. PMID- 26819592 TI - A Neural Network Approach to Intention Modeling for User-Adapted Conversational Agents. AB - Spoken dialogue systems have been proposed to enable a more natural and intuitive interaction with the environment and human-computer interfaces. In this contribution, we present a framework based on neural networks that allows modeling of the user's intention during the dialogue and uses this prediction to dynamically adapt the dialogue model of the system taking into consideration the user's needs and preferences. We have evaluated our proposal to develop a user adapted spoken dialogue system that facilitates tourist information and services and provide a detailed discussion of the positive influence of our proposal in the success of the interaction, the information and services provided, and the quality perceived by the users. PMID- 26819594 TI - Using the Change Manager Model for the Hippocampal System to Predict Connectivity and Neurophysiological Parameters in the Perirhinal Cortex. AB - Theoretical arguments demonstrate that practical considerations, including the needs to limit physiological resources and to learn without interference with prior learning, severely constrain the anatomical architecture of the brain. These arguments identify the hippocampal system as the change manager for the cortex, with the role of selecting the most appropriate locations for cortical receptive field changes at each point in time and driving those changes. This role results in the hippocampal system recording the identities of groups of cortical receptive fields that changed at the same time. These types of records can also be used to reactivate the receptive fields active during individual unique past events, providing mechanisms for episodic memory retrieval. Our theoretical arguments identify the perirhinal cortex as one important focal point both for driving changes and for recording and retrieving episodic memories. The retrieval of episodic memories must not drive unnecessary receptive field changes, and this consideration places strong constraints on neuron properties and connectivity within and between the perirhinal cortex and regular cortex. Hence the model predicts a number of such properties and connectivity. Experimental test of these falsifiable predictions would clarify how change is managed in the cortex and how episodic memories are retrieved. PMID- 26819595 TI - A Fuzzy Integral Ensemble Method in Visual P300 Brain-Computer Interface. AB - We evaluate the possibility of application of combination of classifiers using fuzzy measures and integrals to Brain-Computer Interface (BCI) based on electroencephalography. In particular, we present an ensemble method that can be applied to a variety of systems and evaluate it in the context of a visual P300 based BCI. Offline analysis of data relative to 5 subjects lets us argue that the proposed classification strategy is suitable for BCI. Indeed, the achieved performance is significantly greater than the average of the base classifiers and, broadly speaking, similar to that of the best one. Thus the proposed methodology allows realizing systems that can be used by different subjects without the need for a preliminary configuration phase in which the best classifier for each user has to be identified. Moreover, the ensemble is often capable of detecting uncertain situations and turning them from misclassifications into abstentions, thereby improving the level of safety in BCI for environmental or device control. PMID- 26819593 TI - A System for True and False Memory Prediction Based on 2D and 3D Educational Contents and EEG Brain Signals. AB - We studied the impact of 2D and 3D educational contents on learning and memory recall using electroencephalography (EEG) brain signals. For this purpose, we adopted a classification approach that predicts true and false memories in case of both short term memory (STM) and long term memory (LTM) and helps to decide whether there is a difference between the impact of 2D and 3D educational contents. In this approach, EEG brain signals are converted into topomaps and then discriminative features are extracted from them and finally support vector machine (SVM) which is employed to predict brain states. For data collection, half of sixty-eight healthy individuals watched the learning material in 2D format whereas the rest watched the same material in 3D format. After learning task, memory recall tasks were performed after 30 minutes (STM) and two months (LTM), and EEG signals were recorded. In case of STM, 97.5% prediction accuracy was achieved for 3D and 96.6% for 2D and, in case of LTM, it was 100% for both 2D and 3D. The statistical analysis of the results suggested that for learning and memory recall both 2D and 3D materials do not have much difference in case of STM and LTM. PMID- 26819596 TI - 3D-EAUS and MRI in the Activity of Anal Fistulas in Crohn's Disease. AB - Aim. This study aspires to assess the role of 3D-Endoanal Ultrasound (3D-EAUS) and Magnetic Resonance Imaging (MRI) in preoperative evaluation of the primary tract and internal opening of perianal fistulas, of secondary extensions and abscess. Methods. During 2014, 51 Crohn's disease patients suspected for perianal fistula were enrolled. All patients underwent physical examination with both the methods and subsequent surgery. Results. In the evaluation of CD perianal fistulas, there are no significant differences between 3D-EAUS and MRI in the identification of abscess and secondary extension. Considering the location, 3D EAUS was more accurate than MRI in the detection of intersphincteric fistulas (p value = 10(-6)); conversely, MRI was more accurate than 3D-EAUS in the detection of suprasphincteric fistulas (p value = 0.0327) and extrasphincteric fistulas (p value = 4 ? 10(-6)); there was no significant difference between MRI and 3D-EAUS in the detection of transsphincteric fistulas. Conclusions. Both 3D-EAUS and MRI have a crucial role in the evaluation and detection of CD perianal fistulas. 3D EAUS was preferable to MRI in the detection of intersphincteric fistulas; conversely, in the evaluation of suprasphincteric and extrasphincteric fistulas the MRI was preferable to 3D-EAUS. PMID- 26819597 TI - Techniques for Abdominal Wall Closure after Damage Control Laparotomy: From Temporary Abdominal Closure to Early/Delayed Fascial Closure-A Review. AB - Open abdomen (OA) has been an effective treatment for abdominal catastrophes in traumatic and general surgery. However, management of patients with OA remains a formidable task for surgeons. The central goal of OA is closure of fascial defect as early as is clinically feasible without precipitating abdominal compartment syndrome. Historically, techniques such as packing, mesh, and vacuum-assisted closure have been developed to assist temporary abdominal closure, and techniques such as components separation, mesh-mediated traction, bridging fascial defect with permanent synthetic mesh, or biologic mesh have also been attempted to achieve early primary fascial closure, either alone or in combined use. The objective of this review is to present the challenges of these techniques for OA with a goal of early primary fascial closure, when the patient's physiological condition allows. PMID- 26819598 TI - Radiological Features of Gastrointestinal Lymphoma. AB - Gastrointestinal lymphomas represent 5-20% of extranodal lymphomas and mainly occur in the stomach and small intestine. Clinical findings are not specific, thus often determining a delay in the diagnosis. Imaging features at conventional and cross-sectional imaging must be known by the radiologist since he/she plays a pivotal role in the diagnosis and disease assessment, thus assisting in the choice of the optimal treatment to patients. This review focuses on the wide variety of imaging presentation of esophageal, gastric, and small and large bowel lymphoma presenting their main imaging appearances at conventional and cross sectional imaging, mainly focusing on computed tomography and magnetic resonance, helping in the choice of the best imaging technique for the disease characterization and assessment and the recognition of potential complications. PMID- 26819599 TI - Postcolectomy Peritoneal Environment Increases Colon Cancer Cell Migration Capacity. AB - Background. Clinical data and animal models support an association between postoperative inflammatory response and the risk of colorectal cancer recurrence. Our aim was to evaluate postoperative peritoneal inflammation and its impact on cultured colon cancer cells' migration capacity. Methods. 23 patients undergoing elective colorectal resection with uneventful recovery were prospectively enrolled. Patients were operated on for both malignant and benign etiologies. Peritoneal fluids collected at surgery initiation and after surgery were evaluated for their effect on migration potential of human colon cancer cells using an in vitro scratch assay and on TNF-alpha, IL-1beta, IL-6, and IL-10 levels using bead-based fluorokine-linked multianalyte profiling. Results. Postoperative peritoneal fluid from all patients increased the migration capacity of colon cancer cells compared to preoperative levels. This effect was significant during the first two postoperative days and decreased thereafter. The increase in colon cancer cell migration capacity correlated with increased levels of peritoneal TNF-alpha and IL-10. Conclusion. In this pilot study, we have demonstrated that the intraperitoneal environment following colorectal resection significantly enhances colon cancer cells migration capacity. This effect is associated with postoperative intra-abdominal cytokines level. A larger scale study in colorectal cancer patients is needed in order to correlate these findings with perioperative parameters and clinical outcome. PMID- 26819600 TI - Local and Remote Postconditioning Decrease Intestinal Injury in a Rabbit Ischemia/Reperfusion Model. AB - Intestinal ischemia/reperfusion (I/R) injury is a significant problem that is associated with high morbidity and mortality in critical settings. This injury may be ameliorated using postconditioning protocol. In our study, we created a rabbit intestinal I/R injury model to analyze the effects of local ischemia postconditioning (LIPo) and remote ischemia postconditioning (RIPo) on intestinal I/R injury. We concluded that LIPo affords protection in intestinal I/R injury in a comparable fashion with RIPo by decreasing oxidative stress, neutrophil activation, and apoptosis. PMID- 26819601 TI - Adhesions to Mesh after Ventral Hernia Mesh Repair Are Detected by MRI but Are Not a Cause of Long Term Chronic Abdominal Pain. AB - Aim. The aim of the present study was to perform MRI in patients after ventral hernia mesh repair, in order to evaluate MRI's ability to detect intra-abdominal adhesions. Materials and Methods. Single-center long term follow-up study of 155 patients operated for ventral hernia with laparoscopic (LVHR) or open mesh repair (OVHR), including analyzing medical records, clinical investigation with patient reported pain (VAS-scale), and MRI. MRI was performed in 124 patients: 114 patients (74%) after follow-up, and 10 patients referred for late complaints after ventral mesh repair. To verify the MRI-diagnosis of adhesions, laparoscopy was performed after MRI in a cohort of 20 patients. Results. MRI detected adhesions between bowel and abdominal wall/mesh in 60% of the patients and mesh shrinkage in 20-50%. Adhesions were demonstrated to all types of meshes after both LVHR and OVHR with a sensitivity of 70%, specificity of 75%, positive predictive value of 78%, and negative predictive value of 67%. Independent predictors for formation of adhesions were mesh area as determined by MRI and Charlson index. The presence of adhesions was not associated with more pain. Conclusion. MRI can detect adhesions between bowel and abdominal wall in a fair reliable way. Adhesions are formed both after open and laparoscopic hernia mesh repair and are not associated with chronic pain. PMID- 26819602 TI - Surgical Anatomy of the Gastrointestinal Tract and Its Vasculature in the Laboratory Rat. AB - The aim of this study was to describe and illustrate the morphology of the stomach, liver, intestine, and their vasculature to support the planning of surgical therapeutic methods in abdominal cavity. On adult Wistar rats corrosion casts were prepared from the arterial system and Duracryl Dental and PUR SP were used as a casting medium and was performed macroscopic anatomical dissection of the stomach, liver, and intestine was performed. The rat stomach was a large, semilunar shaped sac with composite lining. On the stomach was very marked fundus, which formed a blind sac (saccus cecus). The rat liver was divided into six lobes, but without gall bladder. Intestine of the rat was simple, but cecum had a shape as a stomach. The following variations were observed in the origin of the cranial mesenteric artery. On the corrosion cast specimens we noticed the presence of the anastomosis between middle colic artery (a. colica media) and left colic artery (a. colica sinistra). We investigated the second anastomosis between middle colic artery and left colic artery. The results of this study reveal that the functional anatomical relationship between the rat stomach, liver and intestine is important for the development of surgical research in human and veterinary medicine. PMID- 26819603 TI - Imaging in the Evaluation of Endoscopic or Surgical Treatment for Achalasia. AB - Purpose. Aim of the study is to evaluate the efficacy of the endoscopic (pneumatic dilation) versus surgical (Heller myotomy) treatment in patients affected by esophageal achalasia using barium X-ray examination of the digestive tract performed before and after the treatment. Materials and Methods. 19 patients (10 males and 9 females) were enrolled in this study; each patient underwent a barium X-ray examination to evaluate the esophageal diameter and the height of the barium column before and after endoscopic or surgical treatment. Results. The mean variation of oesophageal diameter before and after treatment is -2.1 mm for surgery and 1.74 mm for pneumatic dilation (OR 0.167, CI 95% 0.02 1.419, and P: 0.10). The variations of all variables, with the exception of the oesophageal diameter variation, are strongly related to the treatment performed. Conclusions. The barium X-ray study of the digestive tract, performed before and after different treatment approaches, demonstrates that the surgical treatment has to be considered as the treatment of choice of achalasia, reserving endoscopic treatment to patients with high operative risk and refusing surgery. PMID- 26819604 TI - Molecular Analyses of Aspirated Cystic Fluid for the Differential Diagnosis of Cystic Lesions of the Pancreas: A Systematic Review and Meta-Analysis. AB - Background. Researchers have evaluated various molecular tests for improving the differential diagnosis of cystic lesions of the pancreas. Methods. Six electronic databases were searched for articles on molecular tests for the diagnosis of pancreatic cysts. Measures of accuracy were extracted from selected articles and pooled by the random-effects model. Summary receiver operating characteristic curves were used to analyze the overall accuracy of the molecular tests. Pooled sensitivity and specificity values [95% confidence intervals] are reported. Results. The systematic review included eight studies of 428 patients in total. We determined the sensitivities and specificities of tests for KRAS mutations (0.47 [0.39-0.54], 0.98 [0.93-0.99]) and loss of heterozygosity (0.63 [0.54 0.71], 0.76 [0.63-0.87]) for distinguishing mucinous from nonmucinous cysts, as well as the sensitivities and specificities of tests for KRAS mutations (0.59 [0.46-0.71], 0.78 [0.71-0.85]) and loss of heterozygosity (0.89 [0.78-0.96], 0.69 [0.60-0.76]) for differentiating malignant from benign cysts. Conclusion. Tests of KRAS mutations could confirm but not exclude a diagnosis of a mucinous or malignant pancreatic cyst. PMID- 26819606 TI - Intussusception in Adults: The Role of MDCT in the Identification of the Site and Cause of Obstruction. AB - Unlike pediatric intussusception, intestinal intussusception is infrequent in adults and it is often secondary to a pathological condition. The growing use of Multi-Detector Computed Tomography (MDCT) in abdominal imaging has increased the number of radiological diagnoses of intussusception, even in transient and nonobstructing cases. MDCT is well suited to delineate the presence of the disease and provides valuable information about several features, such as the site of intussusception, the intestinal segments involved, and the extent of the intussuscepted bowel. Moreover, MDCT can demonstrate the complications of intussusceptions, represented by bowel wall ischemia and perforation, which are mandatory to promptly refer for surgery. However, not all intussusceptions need an operative treatment. In this paper, we review the current role of MDCT in the diagnosis and management of intussusception in adults, focusing on features, as the presence of a leading point, that may guide an accurate selection of patients for surgery. PMID- 26819605 TI - Clinical Use of Next-Generation Sequencing in the Diagnosis of Wilson's Disease. AB - Objective. Wilson's disease is a disorder of copper metabolism which is fatal without treatment. The great number of disease-causing ATP7B gene mutations and the variable clinical presentation of WD may cause a real diagnostic challenge. The emergence of next-generation sequencing provides a time-saving, cost effective method for full sequencing of the whole ATP7B gene compared to the traditional Sanger sequencing. This is the first report on the clinical use of NGS to examine ATP7B gene. Materials and Methods. We used Ion Torrent Personal Genome Machine in four heterozygous patients for the identification of the other mutations and also in two patients with no known mutation. One patient with acute on chronic liver failure was a candidate for acute liver transplantation. The results were validated by Sanger sequencing. Results. In each case, the diagnosis of Wilson's disease was confirmed by identifying the mutations in both alleles within 48 hours. One novel mutation (p.Ala1270Ile) was found beyond the eight other known ones. The rapid detection of the mutations made possible the prompt diagnosis of WD in a patient with acute liver failure. Conclusions. According to our results we found next-generation sequencing a very useful, reliable, time saving, and cost-effective method for diagnosing Wilson's disease in selected cases. PMID- 26819607 TI - Laparoscopy-Assisted Percutaneous Cholangiography in Biliary Atresia Diagnosis: Comparison with Open Technique. AB - Introduction. Biliary atresia is a surgical cause of prolonged jaundice, which needs to be diagnosed with cholangiography that has traditionally been performed via laparotomy. Laparoscopic assistance has lately been introduced to avoid unnecessary laparotomy. We aim to evaluate the benefits of the laparoscopy assisted cholangiography and compare it to the traditional procedure via laparotomy. Patients and Method. The medical records of the cases who had undergone cholangiography for prolonged jaundice between 2007 and 2014 were analyzed. The patients were grouped according to cholangiography technique (laparotomy/laparoscopy). The laparoscopy and laparotomy groups with patent bile ducts were focused and compared in terms of operation duration, postoperative initiation time of enteral feeding, and full enteral feeding achievement time. Results. Sixty-one infants with prolonged jaundice were evaluated between 2007 and 2014. Among the patients with patent bile ducts, operation duration, postoperative enteral feeding initiation time, and the time to achieve full enteral feeding were shorter in laparoscopy group. Conclusion. Laparoscopic cholangiography is safe and less time-consuming compared to laparotomy, with less postoperative burden. As early age of operation is a very important prognostic factor, laparoscopic evaluation should be an early option in work-up of the infants with prolonged jaundice with direct hyperbilirubinemia, for diagnosis/exclusion of biliary atresia. PMID- 26819608 TI - Diagnosis and Treatment of Biliary Fistulas in the Laparoscopic Era. AB - Biliary fistulas are rare complications of gallstone. They can affect either the biliary or the gastrointestinal tract and are usually classified as primary or secondary. The primary fistulas are related to the biliary lithiasis, while the secondary ones are related to surgical complications. Laparoscopic surgery is a therapeutic option for the treatment of primary biliary fistulas. However, it could be the first responsible for the development of secondary biliary fistulas. An accurate preoperative diagnosis together with an experienced surgeon on the hepatobiliary surgery is necessary to deal with biliary fistulas. Cholecystectomy with a choledocoplasty is the most frequent treatment of primary fistulas, whereas the bile duct drainage or the endoscopic stenting is the best choice in case of minor iatrogenic bile duct injuries. Roux-en-Y hepaticojejunostomy is the extreme therapeutic option for both conditions. The sepsis, the level of the bile duct damage, and the involvement of the gastrointestinal tract increase the complexity of the operation and affect early and late results. PMID- 26819609 TI - Impact of Perioperative Blood Transfusion on Postoperative Complications and Prognosis of Gastric Adenocarcinoma Patients with Different Preoperative Hemoglobin Value. AB - Background. The impact of perioperative blood transfusion on the prognosis of gastric adenocarcinoma patients is still controversial. The aim of this study was to elucidate the impact of perioperative blood transfusion on postoperative complications and prognosis of patients who underwent gastrectomy for gastric adenocarcinoma with different levels of preoperative hemoglobin value (POHb). Method. From 2003 to 2011, 1199 patients who underwent curative gastrectomy were retrospectively enrolled and followed up to December 2014. Clinicopathological features and survival outcomes were compared between transfused and nontransfused patients. Results. In this study, transfused patients had more postoperative complications than nontransfused ones (P = 0.002). In survival analysis, the difference was not significant between transfused and nontransfused patients with POHb between 70 and 100 g/L (P = 0.191). However, in patients with POHb >100 g/L, transfused patients had significantly worse prognosis (P < 0.001), especially in TNM III stage patients (P = 0.002). And intraoperative blood transfusion predicted poor prognosis (P = 0.001). Conclusion. Perioperative blood transfusion might lead to poor survival in gastric adenocarcinoma patients with POHb >100 g/L and transfused patients had more postoperative complications; thus it is better to refrain from unnecessary perioperative blood transfusion especially intraoperative transfusion. PMID- 26819610 TI - A Nationwide Population-Based Study of Corrosive Ingestion in Taiwan: Incidence, Gender Differences, and Mortality. AB - Corrosive injury results from the intake of corrosive-acid-based chemicals. However, this phenomenon is limited to a small number of cases and cannot be extrapolated to the epidemiology of corrosive injuries in actual situations. This study focuses on the annual incidence of corrosive injury and its connection to gender, risk factors, and in-hospital mortality. All patients with corrosive injury (ICD-9 947.0-947.3) were identified using a nationwide inpatient sample from 1996 until 2010. Chi-squared tests and multivariate logistic regression were used to examine risk factors of gender differences and in-hospital mortality of corrosive injury. Young adults comprised the majority of patients (71.2%), and mean age was 44.6 +/- 20.9 years. Women showed a higher incidence rate of corrosive injuries, age, suicide, psychiatric disorder, and systemic complications compared with men (p < 0.001). The present study demonstrated that age (OR = 10.93; 95% CI 5.37-22.27), systemic complications (OR = 5.43; 95% CI 4.61-6.41), malignant neoplasms (OR = 2.23; 95% CI 1.37-3.62), gastrointestinal complications (OR = 2.02; 95% CI 1.63-2.51), chronic disease (OR = 1.30; 95% CI 1.08-1.56), and suicide (OR = 1.23; 95% CI 1.05-1.44) were strongly associated with in-hospital mortality. Educational programs may be helpful for reducing the incidence of ingestion of corrosive chemicals. PMID- 26819611 TI - The Role of MR Enterography in Assessing Crohn's Disease Activity and Treatment Response. AB - MR enterography (MRE) has become the primary imaging modality in the assessment of Crohn's disease (CD) in both children and adults at many institutions in the United States and worldwide, primarily due to its noninvasiveness, superior soft tissue contrast, and lack of ionizing radiation. MRE technique includes distention of the small bowel with oral contrast media with the acquisition of T2 weighted, balanced steady-state free precession, and multiphase T1-weighted fat suppressed gadolinium contrast-enhanced sequences. With the introduction of molecule-targeted biologic agents into the clinical setting for CD and their potential to reverse the inflammatory process, MRE is increasingly utilized to evaluate disease activity and response to therapy as an imaging complement to clinical indices or optical endoscopy. New and emerging MRE techniques, such as diffusion-weighted imaging (DWI), magnetization transfer, ultrasmall superparamagnetic iron oxide- (USPIO-) enhanced MRI, and PET-MR, offer the potential for an expanded role of MRI in detecting occult disease activity, evaluating early treatment response/resistance, and differentiating inflammatory from fibrotic strictures. Familiarity with MR enterography is essential for radiologists and gastroenterologists as the technique evolves and is further incorporated into the clinical management of CD. PMID- 26819612 TI - Capsule Endoscopy for Crohn's Disease: Current Status of Diagnosis and Management. AB - Crohn's disease (CD) is an idiopathic inflammatory bowel disease involving the small and/or large intestine. More than 50% of Western CD patients and up to 88% of Asian CD patients may have small intestinal involvement. Video capsule endoscopy (VCE) has a higher diagnostic yield than small bowel barium radiography and computed tomography enterography for the detection of small intestinal involvement of CD. VCE also provides diagnostic yields comparable to magnetic resonance- (MR-) based enterography or enteroclysis and may have several advantages over MR-based tests for the detection of early small intestinal lesions. Several studies have suggested the use of VCE-based disease activity scoring systems to evaluate small intestinal mucosal disease activity, although their clinical relevance needs to be further studied. A possible indication for VCE is recurrence monitoring after complete surgical excision of CD-involved segments but its usefulness and efficacy compared with conventional endoscopy should be evaluated. The capsule retention rate ranges from 0 to 5.4% in suspected CD patients and from 0 to 13.2% in established CD patients. If VCE is necessary, significant small bowel stricture should be ruled out before VCE by performing a patency capsule study and/or small bowel radiological study in suspected or established CD patients. PMID- 26819613 TI - Capsule Endoscopy for Portal Hypertensive Enteropathy. AB - Portal hypertensive enteropathy (PHE) is a mucosal abnormality of the small bowel that is observed in patients with portal hypertension (PH) and can lead to gastrointestinal bleeding and anemia. The pathogenesis is still not completely understood. The introduction of new endoscopic methods, including capsule endoscopy (CE) or balloon-assisted enteroscopy, has increased the detection of these abnormalities. CE can also serve as a road map for deciding subsequent interventions and evaluating the treatment effect. The prevalence of PHE is reportedly 40-70% in patients with PH. Endoscopic findings can be roughly divided into vascular and nonvascular lesions such as inflammatory-like lesions. Traditionally, PHE-associated factors include large esophageal varices, portal hypertensive gastropathy or colopathy, Child-Turcotte-Pugh class B or C, a history of variceal treatment, and acute gastrointestinal bleeding. More recently, on using scoring systems, a high computed tomography or transient elastography score was reportedly PHE-related factors. However, the prevalence of PHE and its related associated factors remain controversial. The management of PHE has not yet been standardized. It should be individualized according to each patient's situation, the availability of therapy, and each institutional expertise. PMID- 26819614 TI - Application of Different Imaging Methods in the Early Diagnosis of Primary Hepatic Carcinoma. AB - Primary hepatic carcinoma (PHC) is the one of the most common tumors and the common cause of cancer death in the world. Detecting PHC in its early stage by imaging methods may greatly increase survival rates of patients. Ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography/computed tomography are common imaging methods in the diagnosis of PHC. In this paper, the application of different imaging methods in diagnosing the primary hepatic carcinoma will be discussed. PMID- 26819615 TI - Transarterial Embolization and Percutaneous Ethanol Injection as an Effective Bridge Therapy before Liver Transplantation for Hepatitis C-Related Hepatocellular Carcinoma. AB - Background. Transarterial chemoembolization alone or in association with radiofrequency ablation is an effective bridging strategy for patients with hepatocellular carcinoma awaiting for a liver transplant. However, cost of this therapy may limit its utilization. This study was designed to evaluate the outcomes of a protocol involving transarterial embolization, percutaneous ethanol injection, or both methods for bridging hepatocellular carcinomas prior to liver transplantation. Methods. Retrospective review of all consecutive adult patients who underwent a first liver transplant as a treatment to hepatitis C-related hepatocellular carcinoma at our institution between 2002 and 2012. Primary endpoint was patient survival. Secondary endpoint was complete tumor necrosis. Results. Forty patients were analyzed, age 58 +/- 7 years. There were 23 males (57.5%). Thirty-six (90%) out of the total 40 patients were within Milan criteria. Complete necrosis was achieved in 19 patients (47.5%). One-, 3-, and 5 year patient survival were, respectively, 87.5%, 75%, and 69.4%. Univariate analysis did not reveal any variable to impact on overall patient survival. Conclusions. Transarterial embolization, ethanol injection, or the association of both methods followed by liver transplantation comprises effective treatment strategy for hepatitis C-related hepatocellular carcinoma. This strategy should be adopted whenever transarterial chemoembolization and/or radiofrequency ablation are not available options. PMID- 26819616 TI - Small-Bowel Neoplasms: Role of MRI Enteroclysis. AB - Small-bowel neoplasms are the 3%-6% of all gastrointestinal tract neoplasms. Due to the rarity of these lesions, the low index of clinical suspicion, and the inadequate radiologic examinations or incorrect interpretation of radiologic findings, a delay in diagnosis of 6-8 months from the first symptoms often occurs. Even if conventional enteroclysis and capsule endoscopy are the most common procedures used to accurately depict the bowel lumen and mucosal surface, their use in evaluating the mural and extramural extents of small-bowel tumors is limited. Instead multidetector computed tomographic enteroclysis and magnetic resonance enteroclysis have the potential to simultaneously depict intraluminal, mural, and extraintestinal abnormalities. In particular MR enteroclysis has an excellent soft tissue contrast resolution and multiplanar imaging capability. It can provide anatomic, functional, and real time information without the need of ionizing radiation. MR findings, appearances of the lesions, combined with the contrast-enhancement behavior and characteristic of the stenosis are important to differentiate small-bowel neoplasm from other nonneoplastic diseases. PMID- 26819617 TI - Betatrophin Acts as a Diagnostic Biomarker in Type 2 Diabetes Mellitus and Is Negatively Associated with HDL-Cholesterol. AB - Objective. By assessing its circulating concentrations in type 2 diabetes mellitus (T2DM) patients, we aimed to explore the associations of betatrophin with various metabolic parameters and evaluate its diagnostic value in T2DM. Methods. A total of 58 non-diabetes-mellitus (NDM) subjects and 73 age- and sex matched newly diagnosed T2DM patients were enrolled. Correlation analyses between circulating betatrophin levels and multiple metabolic parameters were performed. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of betatrophin concentration in T2DM. Results. Circulating betatrophin levels were approximately 1.8 times higher in T2DM patients than in NDM individuals (median 747.12 versus 407.41 pg/mL, P < 0.001). Correlation analysis showed that betatrophin was negatively associated with high-density lipoprotein cholesterol (HDL-C) levels in all subjects. ROC curve analysis identified betatrophin as a potent diagnostic biomarker for T2DM. The optimal cut off point of betatrophin concentration for predicting T2DM was 501.23 pg/mL. Conclusions. Serum betatrophin levels were markedly increased in newly diagnosed T2DM patients and further elevated in obese T2DM subjects. Betatrophin was negatively correlated with HDL-C levels. Our findings indicate that betatrophin could be a potent diagnostic biomarker for T2DM. PMID- 26819618 TI - Separation and Analysis of Boron Isotope in High Plant by Thermal Ionization Mass Spectrometry. AB - Knowledge of boron and its isotope in plants is useful to better understand the transposition and translocation of boron within plant, the geochemical behavior in the interface between soil and plant, and the biogeochemical cycle of boron. It is critical to develop a useful method to separate boron from the plant for the geochemical application of boron and its isotope. A method was developed for the extraction of boron in plant sample, whose isotope was determined by thermal ionization mass spectrometry. The results indicated that this method of dry ashing coupled with two-step ion-exchange chromatography is powerful for the separation of boron in plant sample with large amounts of organic matters completely. The ratios of boron isotope composition in those plant tissue samples ranged from -19.450/00 to +28.130/00 (total range: 47.580/00) with a mean value of 2.61 +/- 11.760/00 SD. The stem and root isotopic compositions were lower than those in flower and leaf. The molecular mechanism of boron isotope may be responsible for the observed variation of boron isotopic composition and are considered as a useful tool for the better understanding of boron cycling process in the environment and for the signature of living systems. PMID- 26819619 TI - A Case of Eosinophilic Gastroenteritis with Ascites. AB - Eosinophilic gastroenteritis is a rare disorder of unknown cause characterized by focal or diffuse eosinophilic infiltration of gastrointestinal tract, especially the stomach and duodenum. Its clinical presentation depends on which segment of gastrointestinal tract is affected and on the depth of eosinophilic infiltration in the affected segment. We present a case of a 35-year-old male with abdominal distention for six months. Laboratory testing revealed elevated eosinophil count and serum immunoglobulin E (IgE) levels. In abdominal tomography, ascites was observed, and eosinophilic infiltration was detected in duodenum biopsy samples, collected during endoscopic examination of upper gastrointestinal system. Clinical and pathologic findings of the patient responded to steroid dramatically. Even though their comorbidity is rare, eosinophilic gastroenteritis should be considered in differential diagnosis of patients with unspecified ascites. PMID- 26819620 TI - Correlation of Clinicohaematological Parameters in Paediatric Dengue: A Retrospective Study. AB - Dengue is one of the arthropod-borne (arbo) viral diseases transmitted by female mosquito Aedes aegypti. Dengue fever has a wide spectrum of clinical presentation ranging from flu-like illness to severe complicated stage of dengue hemorrhagic fever leading to mortality. This was a retrospective study conducted in a tertiary care hospital in Coastal Karnataka, South India, to know the correlation between the clinical presentation and haematological parameters in the paediatric cases presented with dengue symptoms. A total of 163 paediatric cases who presented fever and dengue-like illness were included in the study. Of which, 69 were confirmed dengue patients. Critical analysis showed that there was a significant difference in the haematological parameters like total leucocyte count, percent differential leucocyte count, and platelets count, in the erythrocyte sedimentation rate (P < 0.05 to 0.0001). Additionally, when compared to nondengue patients, even the liver function and renal function parameters were significantly deranged (P < 0.05 to 0.0001). Stratification based on NS1, IgG, and IgM showed significant alterations in the haematological, hepatic, and renal parameters. With respect to the treatment a small percentage of patients, that is, 8% (4 patients), required platelet transfusion as their counts went below 20,000/MUL. Two patients succumbed to their illness while three required ICU stay. PMID- 26819621 TI - The Role of CAM in Public Health, Disease Prevention, and Health Promotion. PMID- 26819622 TI - Huangqi Jianzhong Tang for Treatment of Chronic Gastritis: A Systematic Review of Randomized Clinical Trials. AB - To assess the clinical effects and safety of Huangqi Jianzhong Tang (HQJZ) for the treatment of chronic gastritis (CG), three English databases and four Chinese databases were searched through the inception to January 2015. In randomized controlled trials (RCTs) comparing HQJZ with placebo, no intervention and western medicine were included. A total of 9 RCTs involving 979 participants were identified. The methodological quality of the included trials was generally poor. Meta-analyses demonstrated that HQJZ plus conventional medicine was more effective in improving overall gastroscopy outcome than western medicine alone for treatment of chronic superficial gastritis with the pooling result of overall improvement [OR 3.78 (1.29,11.06), P = 0.02]. In addition, the combination of HQJZ with antibiotics has higher overall effect rate than antibiotics alone for the treatment of CG [OR 2.60 (1.49,4.54), P = 0.0007]. There were no serious adverse events reported in both the intervention and controlled groups. HQJZ has the potential of improvement of the patients' gastroscopy outcomes, Helicobacter pylori clearance rate, traditional Chinese Medicine syndromes, and overall effect rate alone or in combination use with conventional western medicine for chronic atrophic gastritis. However, due to poor methodological quality, the beneficial effect and safeties of HQJZ for CG could not be confirmed. PMID- 26819623 TI - Antibacterial and Cytotoxic Activity of Compounds Isolated from Flourensia oolepis. AB - The antibacterial and cytotoxic effects of metabolites isolated from an antibacterial extract of Flourensia oolepis were evaluated. Bioguided fractionation led to five flavonoids, identified as 2',4'-dihydroxychalcone (1), isoliquiritigenin (2), pinocembrin (3), 7-hydroxyflavanone (4), and 7,4' dihydroxy-3'-methoxyflavanone (5). Compound 1 showed the highest antibacterial effect, with minimum inhibitory concentration (MIC) values ranging from 31 to 62 and 62 to 250 MUg/mL, against Gram-positive and Gram-negative bacteria, respectively. On further assays, the cytotoxic effect of compounds 1-5 was determined by MTT assay on acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) cell lines including their multidrug resistant (MDR) phenotypes. Compound 1 induced a remarkable cytotoxic activity toward ALL cells (IC50 = 6.6 9.9 MUM) and a lower effect against CML cells (IC50 = 27.5-30.0 MUM). Flow cytometry was used to analyze cell cycle distribution and cell death by PI labeled cells and by Annexin V/PI staining, respectively. Upon treatment, 1 induced cell cycle arrest in the G2/M phase accompanied by a strong induction of apoptosis. These results describe for the first time the antibacterial metabolites of F. oolepis extract, with 1 being the most effective. This chalcone also emerges as a selective cytotoxic agent against sensitive and resistant leukemic cells, highlighting its potential as a lead compound. PMID- 26819624 TI - An improved microtiter plate assay to monitor the oxidative burst in monocot and dicot plant cell suspension cultures. AB - BACKGROUND: A screening method for elicitor and priming agents does not only allow detecting new bioactive substances, it can also be used to understand structure-function relationships of known agents by testing different derivatives of them. This can not only provide new lead compounds for the development of novel, more environment-benign, bio-based agro-chemicals, it may eventually also lead to a better understanding of defense mechanisms in plants. Reactive oxygen species (ROS) are sensitive indicators of these mechanisms but current assay formats are not suitable for multiplex screening, in particularly not in the case of monocot systems. RESULTS: Here we describe continuous monitoring of ROS in 96 well microtiter plates using the chemiluminescent probe L012, a luminol derivative producing chemiluminescence when oxidised by ROS like hydrogen peroxide, superoxide, or hydroxyl radical that can thus be used as an indicator for these ROS. We were able to measure ROS in both monocot (Oryza sativa) and dicot (Medicago truncatula) cell suspension cultures and record dose dependencies for the carbohydrate elicitors and priming agents ulvan and chitosan at low substrate concentrations (0.3-2.5 ug/ml). The method was optimized in terms of cell density, L012 concentration, and pre-incubation time. In contrast to the single peak observed using a cuvette luminometer, the improved method revealed a double burst in both cell systems during the 90-min measuring period, probably due to the detection of multiple ROS rather than only H2O2. CONCLUSION: We provide a medium throughput screening method for monocot and dicot suspension cultured cells that enables direct comparison of monocot and dicot plant systems regarding their reaction to different signaling molecules. PMID- 26819625 TI - Modeling Illicit Drug Use Dynamics and Its Optimal Control Analysis. AB - The global burden of death and disability attributable to illicit drug use, remains a significant threat to public health for both developed and developing nations. This paper presents a new mathematical modeling framework to investigate the effects of illicit drug use in the community. In our model the transmission process is captured as a social "contact" process between the susceptible individuals and illicit drug users. We conduct both epidemic and endemic analysis, with a focus on the threshold dynamics characterized by the basic reproduction number. Using our model, we present illustrative numerical results with a case study in Cape Town, Gauteng, Mpumalanga and Durban communities of South Africa. In addition, the basic model is extended to incorporate time dependent intervention strategies. PMID- 26819626 TI - Plasma calprotectin level: usage in distinction of uncomplicated from complicated acute appendicitis. AB - BACKGROUND: The aim of this study was to identify the diagnostic role of plasma calprotectin value for a distinction of presence acute appendicitis and the indifference of uncomplicated from complicated acute appendicitis. METHODS: Plasma calprotectin, white blood cell and C-reactive protein values of 89 patients, who have undergone laparoscopic appendectomy between January 2013 and May 2013 were evaluated. RESULTS: Calprotectin was 91 ng/mL (range 45-538) for acute appendicitis and 47 ng/ml (range 28-205) for the control group. There was a positive, statistically significant relation between calprotectin and C-reactive protein values (r = 0. 292 p = 0. 001, respectively). There was no statistically significant difference was determined between calprotectin and white blood cell values (r = 0. 142 p = 0. 187, respectively). CRP and Cal values were significantly higher in patients with a complicated AA group than in those with uncomplicated AA (p = 0. 014, p = 0. 0001, respectively) whereas white blood cell counts did not differ significantly between two groups (p = 0. 164). CONCLUSION: Plasma calprotectin levels were increased in patients with acute appendicitis and should use in a distinction of uncomplicated from complicated acute appendicitis patients. PMID- 26819627 TI - Answering Developmental Questions Using Secondary Data. AB - Secondary data analysis of large longitudinal and national data sets is a standard method used in many social sciences to answer complex questions regarding behavior. In this article, we detail the advantages of using these data sets to study developmental questions across the lifespan. First, we provide an overview of how using secondary data can increase studies' scientific integrity. Then, we detail where and how data sets can be obtained that answer specific questions. Finally, we discuss methodological issues related to using longitudinal, population data sets. These data sets can enhance science and test theories by increasing the rigor and generalizability of research to the general population, making secondary data analysis an important method to consider. PMID- 26819628 TI - Combination of ensiling and fungal delignification as effective wheat straw pretreatment. AB - BACKGROUND: Utilization of lignocellulosic feedstocks for bioenergy production in developing countries demands competitive but low-tech conversion routes. White rot fungi (WRF) inoculation and ensiling are two methods previously investigated for low-tech pretreatment of biomasses such as wheat straw (WS). This study was undertaken to assess whether a combination of forced ensiling with Lactobacillus buchneri and WRF treatment using a low cellulase fungus, Ceriporiopsis subvermispora, could produce a relevant pretreatment effect on WS for bioethanol and biogas production. RESULTS: A combination of the ensiling and WRF treatment induced efficient pretreatment of WS by reducing lignin content and increasing enzymatic sugar release, thereby enabling an ethanol yield of 66 % of the theoretical max on the WS glucan, i.e. a yield comparable to yields obtained with high-tech, large-scale pretreatment methods. The pretreatment effect was reached with only a minor total solids loss of 5 % by weight mainly caused by the fungal metabolism. The combination of the biopretreatments did not improve the methane potential of the WS, but improved the initial biogas production rate significantly. CONCLUSION: The combination of the L. buchneri ensiling and C. subvermispora WRF treatment provided a significant improvement in the pretreatment effect on WS. This combined biopretreatment produced particularly promising results for ethanol production. PMID- 26819629 TI - Biomethane potential of industrial paper wastes and investigation of the methanogenic communities involved. AB - BACKGROUND: Cellulose-containing waste products from the agricultural or industrial sector are potentially one of the largest sources of renewable energy on earth. In this study, the biomethane potential (BMP) of two types of industrial paper wastes, wood and pulp residues (WR and PR, respectively), were evaluated under both mesophilic and thermophilic conditions, and various pretreatment methods were applied in the attempt to increase the methane potential during anaerobic digestion. The methanogenic community composition was investigated with denaturing gradient gel electrophoresis (DGGE) and the ANAEROCHIP microarray, and dominant methanogens were quantitated using quantitative PCR. RESULTS: All pretreatments investigated in this study with the exception of the alkaline pretreatment of PR were found to increase the BMP of two paper industry wastes. However, the low recalcitrance level of the PR resulted in the pretreatments being less effective in increasing BMP when compared with those for WR. These results were supported by the physico-chemical data. A combined application of ultrasound and enzymatic pretreatment was found to be the best strategy for increasing methane yields. The retention time of substrates in the reactors strongly influenced the BMP of wastes subjected to the different pretreatments. In sludges from both paper wastes subjected to the various pretreatments, mixotrophic Methanosarcina species were found to dominate the community, accompanied by a consortium of hydrogenotrophic genera. CONCLUSIONS: Pretreating industrial paper wastes could be a potentially viable option for increasing the overall degradation efficiency and decreasing reactor retention time for the digestion of complex organic matter such as lignocellulose or hemicellulose. This would help reduce the environmental burden generated from paper production. Although there were minor differences in the methanogenic communities depending on the temperature of anaerobic digestion, there was little effect of substrate and pretreatment type on the community composition. Thus, methanogen community dynamics would not seem to be an appropriate indicator regarding BMP in the AD processes investigated. PMID- 26819630 TI - Chromosomal copy number analysis on chorionic villus samples from early spontaneous miscarriages by high throughput genetic technology. AB - BACKGROUND: About 10 -15 % of all clinically recognized pregnancies result in spontaneous miscarriages, and chromosomal abnormalities are the most common reason. The conventional karyotyping on chorionic villus samples (CVSs) is limited by cell culture and its resolution. This study aimed at evaluating the efficiency of the application of high throughput genetic technology, including array comparative genomic hybridization (array CGH) and next generation sequencing (NGS) on the chromosomal copy number analysis of CVSs from early spontaneous miscarriages. RESULTS: Four hundred and thirty-six CVSs from early spontaneous abortion were collected. Genomic DNA was extracted using a routine method, and the chromosomal copy number variants (CNVs) were analyzed by array CGH and NGS. Two hundred and twenty-five samples (51.6 %) with abnormal chromosomes were identified among 436 samples, of which 188 samples (41.3 %) were aneuploidy, 23 samples (5.3 %) were segmental deletion and/or duplication cases, and 14 samples (3.2 %) were triploid. Two of the three cases with small segmental deletion and duplication were validated to be transferred from their fathers who were carriers of submicroscopic reciprocal translocation. CONCLUSION: A high chromosomal abnormality detection rate on CVSs from early spontaneous miscarriage was achieved by array CGH and NGS. Specifically, the detection of submicroscopic recombination, which is sometimes missed by conventional karyotyping, was important for genetic counseling for the couples that suffered from recurrent miscarriages. PMID- 26819631 TI - The prediction accuracy of dynamic mixed-effects models in clustered data. AB - BACKGROUND: Clinical prediction models often fail to generalize in the context of clustered data, because most models fail to account for heterogeneity in outcome values and covariate effects across clusters. Furthermore, standard approaches for modeling clustered data, including generalized linear mixed-effects models, would not be expected to provide accurate predictions in novel clusters, because such predictions are typically based on the hypothetical mean cluster. We hypothesized that dynamic mixed-effects models, which incorporate data from previous predictions to refine the model for future predictions, would allow for cluster-specific predictions in novel clusters as the model is updated over time, thus improving overall model generalizability. RESULTS: We quantified the potential gains in prediction accuracy from using a dynamic modeling strategy in a simulation study. Furthermore, because clinical prediction models in the context of clustered data often involve outcomes that are dependent on patient volume, we examined whether using dynamic mixed-effects models would be robust to misspecification of the volume-outcome relationship. Our results indicated that dynamic mixed-effects models led to substantial improvements in prediction accuracy in clustered populations over a broad range of conditions, and were uniformly superior to static models. In addition, dynamic mixed-effects models were particularly robust to misspecification of the volume-outcome relationship and to variation in the frequency of model updating. The extent of the improvement in prediction accuracy that was observed with dynamic mixed-effects models depended on the relative impact of fixed and random effects on the outcome as well as the degree of misspecification of model fixed effects. CONCLUSIONS: Dynamic mixed-effects models led to substantial improvements in prediction model accuracy across a broad range of simulated conditions. Therefore, dynamic mixed effects models could be a useful alternative to standard static models for improving the generalizability of clinical prediction models in the setting of clustered data, and, thus, well worth the logistical challenges that may accompany their implementation in practice. PMID- 26819632 TI - SequenceCEROSENE: a computational method and web server to visualize spatial residue neighborhoods at the sequence level. AB - BACKGROUND: To understand the molecular function of biopolymers, studying their structural characteristics is of central importance. Graphics programs are often utilized to conceive these properties, but with the increasing number of available structures in databases or structure models produced by automated modeling frameworks this process requires assistance from tools that allow automated structure visualization. In this paper a web server and its underlying method for generating graphical sequence representations of molecular structures is presented. RESULTS: The method, called SequenceCEROSENE (color encoding of residues obtained by spatial neighborhood embedding), retrieves the sequence of each amino acid or nucleotide chain in a given structure and produces a color coding for each residue based on three-dimensional structure information. From this, color-highlighted sequences are obtained, where residue coloring represent three-dimensional residue locations in the structure. This color encoding thus provides a one-dimensional representation, from which spatial interactions, proximity and relations between residues or entire chains can be deduced quickly and solely from color similarity. Furthermore, additional heteroatoms and chemical compounds bound to the structure, like ligands or coenzymes, are processed and reported as well. To provide free access to SequenceCEROSENE, a web server has been implemented that allows generating color codings for structures deposited in the Protein Data Bank or structure models uploaded by the user. Besides retrieving visualizations in popular graphic formats, underlying raw data can be downloaded as well. In addition, the server provides user interactivity with generated visualizations and the three-dimensional structure in question. CONCLUSIONS: Color encoded sequences generated by SequenceCEROSENE can aid to quickly perceive the general characteristics of a structure of interest (or entire sets of complexes), thus supporting the researcher in the initial phase of structure-based studies. In this respect, the web server can be a valuable tool, as users are allowed to process multiple structures, quickly switch between results, and interact with generated visualizations in an intuitive manner. The SequenceCEROSENE web server is available at https://biosciences.hs mittweida.de/seqcerosene. PMID- 26819633 TI - Association between iron status and thyroid function in Nepalese children. AB - BACKGROUND: Deficiencies of iodine and iron may have adverse effect on thyroid function. This study was undertaken to investigate the association between iron status and thyroid function in Nepalese children living in hilly regions. METHODS: A cross-sectional study was conducted among 227 school children aged 6 12 years living in hilly regions of eastern Nepal. Urine and blood samples were analyzed for urinary iodine concentration, free thyroxine, free triiodothyronine, thyroid stimulating hormone, hemoglobin, serum iron and total iron binding capacity, and percentage transferrin saturation was calculated. RESULTS: The cohort comprised euthyroid (80.6 %, n = 183), overt hypothyroid (1.3 %, n = 3), subclinical hypothyroid (16.3 %, n = 37) and subclinical hyperthyroid (1.8 %, n = 4) children respectively. About 35.2 % (n = 80) children were anemic, 43.6 % (n = 99) were iron deficient and 19.8 % (n = 45) had urinary iodine excretion < 100 MUg/L. Hypothyroidism (overt and subclinical) was common in anemic and iron deficient children. The relative risk of having hypothyroidism (overt and subclinical) in anemic and iron deficient children was 5.513 (95 % CI: 2.844 10.685, p < 0.001) and 1.939 (95 % CI: 1.091-3.449, p = 0.023) respectively as compared to non-anemic and iron sufficient children. Thyroid stimulating hormone had significant negative correlation with hemoglobin (r = -0.337, p < 0.001) and transferrin saturation (r = -0.204, p = 0.002). CONCLUSIONS: Thyroid dysfunction, iron deficiency and anemia are common among Nepalese children. In this cohort, anemic and iron deficient children had poor thyroid function. PMID- 26819634 TI - Survival and Symptom Relief after Palliative Radiotherapy for Esophageal Cancer. AB - PURPOSE: The aim of this study was to assess the 6-months dysphagia-free survival, improvement in swallowing function, complication rate, and overall survival in patients with incurable esophageal cancer treated with palliative radiotherapy. METHODS: We retrospectively reviewed data from 139 patients (median age 72 years) with advanced/recurrent incurable esophageal cancer, who were referred to 3 German radiation oncology centers for palliative radiotherapy between 1994 and 2014. Radiotherapy consisted of external beam radiotherapy (EBRT) with 30 - 40.5 Gy/2.5 - 3 Gy per fraction, brachytherapy alone (BT) with 15 - 25 Gy/5 - 7Gy per fraction/weekly and EBRT + BT (30 - 40.5 Gy plus 10 - 14 Gy with BT) in 65, 46, and 28 patients, respectively. Dysphagia-free survival (Dy PFS) was defined as the time to worsening of dysphagia for at least one point, a new loco-regional failure or death of any cause. RESULTS: Median follow-up time was 6 months (range 1-6 months). Subjective symptom relief was achieved in 72 % of patients with median response duration of 5 months. The 1-year survival rate was 30%. The 6-months Dy-PFS time for the whole group was 73 +/- 4%. The 6-months Dy-PFS was 90 +/- 4% after EBRT, 92 +/- 5% after EBRT + BT and 37 +/- 7% after BT, respectively (p<0.001). Five patients lived for more than 2 years, all of them were treated with EBRT +/- BT. Ulceration, fistula and stricture developed in 3, 6 and 7 patients, respectively. CONCLUSIONS: Radiotherapy leads to symptom improvement in the majority of patients with advanced incurable esophageal cancer. The present results favor EBRT +/- BT over BT alone. Due to the retrospective nature of this study, imbalances in baseline characteristics might have contributed to this finding, and further trials appear necessary. PMID- 26819635 TI - Nutritional Support in Cancer Patients: A Position Paper from the Italian Society of Medical Oncology (AIOM) and the Italian Society of Artificial Nutrition and Metabolism (SINPE). AB - Malnutrition is a frequent problem in cancer patients, which leads to prolonged hospitalization, a higher degree of treatment-related toxicity, reduced response to cancer treatment, impaired quality of life and a worse overall prognosis. The attitude towards this issue varies considerably and many malnourished patients receive inadequate nutritional support. We reviewed available data present in the literature, together with the guidelines issued by scientific societies and health authorities, on the nutritional management of patients with cancer, in order to make suitable and concise practical recommendations for appropriate nutritional support in this patient population. Evidence from the literature suggests that nutritional screening should be performed using validated tools (the Nutritional Risk Screening 2002 [NRS 2002], the Malnutrition Universal Screening Tool [MUST], the Malnutrition Screening Tool [MST] and the Mini Nutritional Assessment [MNA]), both at diagnosis and at regular time points during the course of disease according to tumor type, stage and treatment. Patients at nutritional risk should be promptly referred for comprehensive nutritional assessment and support to clinical nutrition services or medical personnel with documented skills in clinical nutrition, specifically for cancer patients. Nutritional intervention should be actively managed and targeted for each patient; it should comprise personalized dietary counseling and/or artificial nutrition according to spontaneous food intake, tolerance and effectiveness. Nutritional support may be integrated into palliative care programs. "Alternative hypocaloric anti-cancer diets" (e.g. macrobiotic or vegan diets) should not be recommended as they may worsen nutritional status. Well designed clinical trials are needed to further our knowledge of the nutritional support required in different care settings for cancer patients. PMID- 26819636 TI - Clinical Practice in the Use of Adjuvant Chemotherapy for Patients with Colon Cancer in South Korea: a Multi-Center, Prospective, Observational Study. AB - BACKGROUND: Adjuvant chemotherapy is a crucial part of treatment for patients with locally advanced colon cancer. This study was conducted to investigate the actual practice in the use of adjuvant chemotherapy for patients with high-risk stage II or stage III colon cancer in South Korea. METHODS: This was a 24-month open-label, prospective, observational study conducted at 12 centers across South Korea. Patients with high-risk stage II and stage III colon cancer receiving adjuvant chemotherapy after curative surgery were included, and data were collected at baseline, third, and sixth month. RESULTS: A total of 246 patients were included in the analyses. Of five available regimens (FOLFOX, CAPOX, 5 FU/LV, capecitabine, and UFT/LV), FOLFOX was most commonly used (82.5%). Investigators indicated the "efficacy" as the major cause for selecting FOLFOX or CAPOX. For 5-FU/LV, capecitabine, or UFT/LV, the "safety" or "patient's characteristics (age, comorbidity, and stage)" was one of the most important selecting factors. Patients receiving 5-FU/LV, capecitabine, or UFT/LV had older age, worse PS and lower disease stage (stage II) than patients receiving FOLFOX or CAPOX. Hematologic toxicities were the most common cause of dose adjustment and treatment delay. CONCLUSIONS: In South Korea, FOLFOX was the most commonly used regimen for adjuvant chemotherapy and its efficacy was the main cause for selecting this regimen. Patients receiving 5-FU/LV, capecitabine, or UFT/LV had older age, worse PS and lower disease stage (stage II) than patients receiving FOLFOX or CAPOX. PMID- 26819637 TI - The association between RFC1 G80A polymorphism and cancer susceptibility: Evidence from 33 studies. AB - Aberrant folate metabolism is closely related to tumorigenesis. Genetic variations in the Reduced folate carrier 1 (RFC1) may alter the progress of folate metabolism, and thereby cause the initiation and progress of the cancer. Considerable studies have performed to investigate the association between RFC1 G80A (rs1051266) polymorphism and cancer susceptibility, but the conclusions were conflicting. Therefore, we conducted a meta-analysis to reevaluate the association of RFC1 G80A polymorphism with cancer risk. PubMed and EMBASE were searched for eligible studies. The association of RFC1 G80A polymorphism and cancer risk was evaluated by the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). The significant association was found between RFC1 G80A polymorphism and hematological malignance susceptibility (A vs. G: OR=1.11, 95%CI=1.003-1.23, P=0.045; GA vs. GG: OR=1.18, 95%CI=1.06-1.31, P=0.002; AA+GA vs. GG: OR=1.18, 95%CI=1.07-1.29, P=0.001). Stratified analysis by ethnicity indicated that the association became more prominent among Caucasians (GA vs. GG: OR=1.28, 95%CI=1.12-1.45, P<0.001; AA+GA vs. GG: OR=1.21, 95%CI=1.08-1.36, P=0.001). In term of the cancer type, this polymorphism significantly increased the risk of acute lymphoblast leukemia (GA vs. GG: OR=1.13, 95%CI=1.001-1.28, P=0.048; AA+GA vs. GG: OR=1.28, 95%CI=1.13-1.46, P<0.001) and acute myeloid leukemia (GA vs. GG: OR=2.57, 95%CI=1.37-4.85, P=0.003). No significant association between RFC1 G80A polymorphism and overall solid cancer risk was observed, but a protective association with digestive cancer risk was found (GA vs. GG: OR=0.89, 95%CI= 0.81-0.99, P=0.030). The comprehensive meta-analysis encouraged the notion that RFC1 G80A polymorphism may play an important role in hematopoietic system malignance. These findings need further validation in the large multicenter investigations. PMID- 26819639 TI - Identification of the Factors Responsible for the Selective in vitro Cytotoxic Activity of Isoprenylated Coumarin Derivatives under Nutrient-deprived Conditions. AB - Pancreatic cancer is one of the most devastating forms of human cancer. The lack of effective clinical treatments for pancreatic cancer has led to one of the lowest five-year survival rates among all cancers. Recently, our laboratory has developed a novel series of isoprenylated coumarin derivatives that have exhibited anti-pancreatic cancer activity exclusively under nutrient-deprived conditions. In this study, we report the effect of the various cell culture medium components on the preferential cytotoxicity of our lead isoprenylated coumarin compound against the pancreatic adenocarcinoma cell line PANC-1. In particular, our findings show a clear link between observed cytotoxicity and glucose deprivation, suggesting that our compound targets a salvage pathway when glycolysis is no longer an option for cancer cell survival. The cytotoxicity of our lead compound was also examined in vitro against two other pancreatic cancer cell lines, BxPC-3 and Capan-2 under both nutrient-rich and nutrient-deprived conditions. PMID- 26819640 TI - Comparison of Clinicopathological Features and Prognosis in Triple-Negative and Non-Triple Negative Breast Cancer. AB - PURPOSE: Triple-negative breast cancer (TNBC) has attracted more attention both clinically and experimentally because of its high-risk biological characteristics and lacking of effective treatment method. The purpose of this retrospective study was to find out the incidence of triple-negative breast cancer (TNBC) in all kinds of breast cancers and to compare and analyze the clinicopathological features, recurrence, metastasis and prognosis of patients with TNBC and non triple negative breast cancer (non-TNBC). METHODS: A total of 1578 female patients with primary breast cancer were diagnosed and treated at the department of General Surgery, the Chinese PLA General Hospital, China, from Jan. 2004 to Jun. 2009. The 1578 breast cancer patients were divided into two groups: the TNBC group and the non-TNBC group. The clinical features and prognosis of the two groups were compared. RESULTS: The incidence of TNBC was 20.41%. Compared with the non-TNBC, the TNBC were characterized as younger age, higher histological grade, higher rate of positive lymph node, bigger tumor size, higher clinical stage at diagnosis, higher histological grade, quicker and easier recurrence and metastasis and lower 5-year DFS rate and 5-year OS rate. The metastasis of TNBC had obvious organic tendency. The lungs, liver and brain were the first three most common sites of metastases. The information of age, the tumor size, lymph node status, clinical stage, histological grade, pathological types and operation method, especially the age and lymph node status play the important roles in judging the prognosis of TNBC. CONCLUSIONS: According to this study we found that TNBC was a distinct subgroup of breast cancer with particular clinicopathologic behavior. Compared with the non-TNBC, TNBC was characterized by more aggressive behavior, and lower DFS and OS rate. The metastasis of TNBC had obvious organic tendency. The information of age, the maximum diameter of the tumor, lymph node status, clinical stage, histological grade, pathological types and operation method, especially the age and lymph node status played the important roles in judging the prognosis of TNBC patients. PMID- 26819638 TI - DEC1 and DEC2 Crosstalk between Circadian Rhythm and Tumor Progression. AB - Clock genes, major regulators of circadian rhythm, are involved in tumor progression. We have shown that clock genes basic helix-loop-helix (BHLH) transcription factors, differentiated embryonic chondrocyte gene 1 (DEC1/BHLHE40/Sharp2/Stra13) and DEC2 (BHLHE41/Sharp1) play important roles in circadian rhythm, cell proliferation, apoptosis, hypoxia response, various stresses, and epithelial-to-mesenchymal transition (EMT) of tumor cells. Various stresses, such as exposure to transforming growth factor-beta (TGF-beta), hypoxia, cytokines, serum-free, and anti-tumor drugs affect DEC1 and DEC2 expression. An increased or decreased expression of DEC1 and DEC2 regulated tumor progression. However, DEC1 and DEC2 have opposite effects in tumor progression, where the reason behind remains unclear. We found that DEC2 has circadian expression in implanted mouse sarcoma cells, suggesting that DEC2 regulates tumor progression under circadian rhythm. In addition to that, we showed that DEC1 and DEC2 regulate target genes via positive or negative feedback system in tumor progression. We propose that DEC1 and DEC2 act as an accelerator or a brake in tumor progression. In this review, we summarize current progress of knowledge in the function of DEC1 and DEC2 genes in tumor progression. PMID- 26819642 TI - Adenovirus-Mediated Angiotensin II Type 2 Receptor Overexpression Inhibits Tumor Growth of Prostate Cancer In Vivo. AB - The renin-angiotensin system (RAS) plays important roles in tumorigenesis and is involved with several hallmarks of cancer. Evidence shows that angiotensin II (AngII) type 1 receptor (AT1R) blockers may be associated with improved outcome in prostate cancer patients. Furthermore, our previous studies indicate that increased expression of Ang II type 2 receptor (AT2R) alone induced apoptosis in human prostate cancer lines, an effect that did not require Ang II. This study aimed to investigate the effects of AT2R on tumor growth in vivo and we hypothesized that AT2R over-expression would inhibit proliferation and induce apoptosis in vivo. Human prostate cancer DU145 xenograft mouse model was used to assess the effect of AT2R on tumor growth in vivo. Mice bearing a palpable tumor were chosen and divided randomly into three treatment groups: AT2R, GFP, and PBS. Then we directly injected into the xenograft tumors of the mice every three days with recombinant adenoviruses encoding AT2R (Ad5-CMV-AT2R-EGFP), EGFP (Ad5-CMV EGFP) and PBS, respectively. The tumor sizes of the tumor bearing mice were then measured. Immunohistochemical Ki-67 staining and TUNEL assay were performed to examine the inhibitory effect of AT2R on tumor cell proliferation. The results showed that AT2R overexpression can inhibit tumor growth of prostate cancer in vivo by inhibiting proliferation and inducing apoptosis of tumor cells. GADD45A is involved in the AT2R-induced antitumor activity. This suggests that AT2R is a potentially useful gene for prostate gene therapy. PMID- 26819641 TI - Colorectal Carcinogenesis, Radiation Quality, and the Ubiquitin-Proteasome Pathway. AB - Adult colorectal epithelium undergoes continuous renewal and maintains homeostatic balance through regulated cellular proliferation, differentiation, and migration. The canonical Wnt signaling pathway involving the transcriptional co-activator beta-catenin is important for colorectal development and normal epithelial maintenance, and deregulated Wnt/beta-catenin signaling has been implicated in colorectal carcinogenesis. Colorectal carcinogenesis has been linked to radiation exposure, and radiation has been demonstrated to alter Wnt/beta-catenin signaling, as well as the proteasomal pathway involved in the degradation of the signaling components and thus regulation of beta-catenin. The current review discusses recent progresses in our understanding of colorectal carcinogenesis in relation to different types of radiation and roles that radiation quality plays in deregulating beta-catenin and ubiquitin-proteasome pathway (UPP) for colorectal cancer initiation and progression. PMID- 26819643 TI - Effects of Lovastatin on MDA-MB-231 Breast Cancer Cells: An Antibody Microarray Analysis. AB - Despite the tremendous improvement in cancer therapeutics, treatment of late stage breast cancer remains a challenge for both basic scientists and clinicians. Lovastatin, a natural product derived from Aspergillus terreus or Monascus ruber, has been widely used as cholesterol-lowing drug in the clinic. It also has anti cancer properties through poorly defined molecular mechanisms. In the present study, we employed a novel antibody microarray technology to investigate the molecular mechanisms through which lovastatin inhibits breast cancer. We found that lovastatin up-regulated 17 proteins and down-regulated 20 proteins in MDA-MB 231 breast cancer cells. These included proteins that modulate apoptosis, cell proliferation, differentiation, signal transduction, epithelial-to-mesenchymal transition and tumor metastasis. Modulation of these pathways may mediate, in part, the inhibitory activity of lovastatin on breast cancer. PMID- 26819644 TI - What Is the Appropriate Clinical Target Volume for Esophageal Squamous Cell Carcinoma? Debate and Consensus Based on Pathological and Clinical Outcomes. AB - Accurate delineation of clinical target volume (CTV) is critical in the effective management of squamous cell carcinoma (SCC) of esophagus using radiation therapy. Accurate delineation may improve the probability of local control and reduce the risk of complications. However, there are no consistent standards on the proper size of the margins added to the gross tumor volume (GTV). Different institutions and radiation oncologists have discordant opinions. In this paper, we review pathological and clinical outcomes to determine the most appropriate CTV for squamous cell carcinomas (SCC) of esophagus. The CTV for esophageal carcinoma should ensure that all subclinical lesions are encompassed regardless of the physical distance. The most precise method for delineating a reasonable CTV is to combine advanced imaging techniques, such as PET/CT and EUS, which allows the detection and prediction of subclinical lesions based on tumor characteristics such as the pathological type, differentiation, T disease, length and lymph node status. PMID- 26819645 TI - Expression of TMEM207 in Colorectal Cancer: Relation between TMEM207 and Intelectin-1. AB - Recent research advances highlighted an intestinal goblet cell-produced lectin, intelectin-1 (also known as omentin-1), as a tumor suppressor. One study indicated that downregulation of intelectin-1 may be related to the unfavorable prognosis among patients with colorectal carcinoma at an advanced stage. The present study was aimed at analyzing the expression of a hitherto uncharacterized transmembrane protein TMEM207 in colorectal carcinoma, and we found that the TMEM207 function is linked to intelectin-1 processing. With specific antibodies, TMEM207 immunoreactivity was detected in 38 of 216 colorectal cancer tissue samples. TMEM207 immunoreactivity correlated inversely with lymph node metastatic status (p < 0.01). TMEM207 expression significantly correlated with the mucinous phenotype of colorectal carcinoma. A coimmunoprecipitation assay revealed an interaction between intelectin-1 and TMEM207 in colorectal cancer cells. A proximal ligation assay indicated that intelectin-1 and TMEM207 were colocalized to the cytoplasm of the colorectal cancer cells. A small-interfering-RNA-mediated knockdown of TMEM207 increased polyubiquitination and proteasome degradation of intelectin-1 in cultured colorectal cancer cells and decreased intelectin-1 secretion. These findings indicate that a loss of TMEM207 expression leads to insufficient intelectin-1 production thus promoting colorectal carcinogenesis. PMID- 26819646 TI - Genome-wide Analysis of Epstein-Barr Virus (EBV) Integration and Strain in C666-1 and Raji Cells. AB - EBV is a key risk factor for many malignancy diseases such as nasopharyngeal carcinoma (NPC) and Burkitt lymphoma (BL). EBV integration has been reported, but its scale and impact to cancer development is remains unclear. C666-1 (NPC cell line) and Raji (BL cell line) are commonly studied EBV-positive cancer cells. A rare few EBV integration sites in Raji were found in previous research by traditional methods. To deeply survey EBV integration, we sequenced C666-1 and Raji whole genomes by the next generation sequencing (NGS) technology and a total of 909 breakpoints were detected in the two cell lines. Moreover, we observed that the number of integration sites was positive correlated with the total amount of chromosome structural variations (SVs) and copy number structural variations (CNVs), and most breakpoints located inside or nearby genome structural variations regions. It suggested that host genome instability provided an opportunity for EBV integration on one hand and the integration aggravated host genome instability on the other hand. Then, we respectively assembled the C666-1 and Raji EBV strains which would be useful resources for EBV-relative studies. Thus, we report the most comprehensive characterization of EBV integration in NPC cell and BL cell, and EBV shows the wide range and random integration to increase the tumorigenesis. The NGS provides an incomparable level of resolution on EBV integration and a convenient approach to obtain viral strain compared to any research technology before. PMID- 26819648 TI - Comparison of Thresholds for Pulmonary Capillary Hemorrhage Induced by Pulsed wave and B-mode Ultrasound. AB - Pulsed ultrasound was found to induce pulmonary capillary hemorrhage (PCH) in mice about 25 years ago but remains a poorly understood risk factor for pulmonary diagnostic ultrasound. In early research using laboratory fixed beam ultrasound, thresholds for PCH had frequency variation from 1-4 MHz similar to the Mechanical Index. In recent research, thresholds for B mode diagnostic ultrasound from 1.5 12 MHz had little dependence on frequency. To compare the diagnostic ultrasound method to laboratory pulsed exposure, thresholds for fixed beam ultrasound were determined using comparable methods at 1.5 and 7.5 MHz. PCH thresholds were lower for simple fixed-beam pulse modes than for B mode and in approximate agreement with early research. However, for comparable timing parameters, PCH thresholds had little dependence on ultrasonic frequency. These findings suggest that the MI may not be directly useful as a dosimetric parameter for safety guidance in pulmonary ultrasound. PMID- 26819647 TI - Genome-wide DNA methylation analysis of pseudohypoparathyroidism patients with GNAS imprinting defects. AB - BACKGROUND: Pseudohypoparathyroidism (PHP) is caused by (epi)genetic defects in the imprinted GNAS cluster. Current classification of PHP patients is hampered by clinical and molecular diagnostic overlaps. The European Consortium for the study of PHP designed a genome-wide methylation study to improve molecular diagnosis. METHODS: The HumanMethylation 450K BeadChip was used to analyze genome-wide methylation in 24 PHP patients with parathyroid hormone resistance and 20 age- and gender-matched controls. Patients were previously diagnosed with GNAS specific differentially methylated regions (DMRs) and include 6 patients with known STX16 deletion (PHP(Deltastx16)) and 18 without deletion (PHP(neg)). RESULTS: The array demonstrated that PHP patients do not show DNA methylation differences at the whole-genome level. Unsupervised clustering of GNAS-specific DMRs divides PHP(Deltastx16) versus PHP(neg) patients. Interestingly, in contrast to the notion that all PHP patients share methylation defects in the A/B DMR while only PHP(Deltastx16) patients have normal NESP, GNAS-AS1 and XL methylation, we found a novel DMR (named GNAS-AS2) in the GNAS-AS1 region that is significantly different in both PHP(Deltastx16) and PHP(neg), as validated by Sequenom EpiTYPER in a larger PHP cohort. The analysis of 58 DMRs revealed that 8/18 PHP(neg) and 1/6 PHP(Deltastx16) patients have multi-locus methylation defects. Validation was performed for FANCC and SVOPL DMRs. CONCLUSIONS: This is the first genome-wide methylation study for PHP patients that confirmed that GNAS is the most significant DMR, and the presence of STX16 deletion divides PHP patients in two groups. Moreover, a novel GNAS-AS2 DMR affects all PHP patients, and PHP patients seem sensitive to multi-locus methylation defects. PMID- 26819649 TI - Monophasic Pulsed 200-MUA Current Promotes Galvanotaxis With Polarization of Actin Filament and Integrin alpha2beta1 in Human Dermal Fibroblasts. AB - OBJECTIVE: The monophasic pulsed microcurrent is used to promote wound healing, and galvanotaxis regulation has been reported as one of the active mechanisms in the promotion of tissue repair with monophasic pulsed microcurrent. However, the optimum monophasic pulsed microcurrent parameters and intracellular changes caused by the monophasic pulsed microcurrent have not been elucidated in human dermal fibroblasts. The purpose of this study was to investigate the optimum intensity for promoting galvanotaxis and the effects of electrical stimulation on integrin alpha2beta1 and actin filaments in human dermal fibroblasts. METHODS: Human dermal fibroblasts were treated with the monophasic pulsed microcurrent of 0, 100, 200, or 300 MUA for 8 hours, and cell migration and cell viability were measured 24 hours after starting monophasic pulsed microcurrent stimulation. Polarization of integrin alpha2beta1 and lamellipodia formation were detected by immunofluorescent staining 10 minutes after starting monophasic pulsed microcurrent stimulation. RESULTS: The migration toward the cathode was significantly higher in the cells treated with the 200-MUA monophasic pulsed microcurrent than in the controls (P < .01) without any change in cell viability; treatment with 300-MUA monophasic pulsed microcurrent did not alter the migration ratio. The electrostimulus of 200 MUA also promoted integrin alpha2beta1 polarization and lamellipodia formation at the cathode edge (P < .05). CONCLUSION: The results show that 200 MUA is an effective monophasic pulsed microcurrent intensity to promote migration toward the cathode, and this intensity could regulate polarization of migration-related intracellular factors in human dermal fibroblasts. PMID- 26819650 TI - Does Time Affect Patient Satisfaction and Health-Related Quality of Life After Reduction Mammoplasty? AB - OBJECTIVE: A total of 62,611 patients with breast hypertrophy underwent breast reduction surgery in 2013 in the United States to improve their symptoms and health-related quality of life. While multiple studies utilizing various outcome instruments demonstrate the efficacy of reductive surgery, it is presently unknown how the postoperative course affects patient satisfaction and health related quality of life as measured by the BREAST-Q. Our objective was to determine the temporal relationship of patient satisfaction and health-related quality of life after reduction mammoplasty. METHODS: Patients prospectively completed the BREAST-Q reduction mammoplasty module at 3 time points during their treatment: preoperatively, at less than 3 months postoperatively, and at more than 3 months (<12 months) postoperatively. A single surgeon (N.P.P.) performed all of the breast reduction procedures. RESULTS: Each time point contained 20 questionnaires. Mean preoperative BREAST-Q scores were significantly lower than scores at the less than 3-month postoperative time point for the scales Satisfaction With Breasts, Psychosocial Well-being, Sexual Well-being, and Physical Well-being (P < .001). There was no significant difference in BREAST-Q scores between the postoperative time points in these measures. CONCLUSION: Breast reduction surgery offers a vast improvement in patients' satisfaction and health-related quality of life that is maintained throughout the postoperative period. These findings can assist surgeons in managing patient expectations after reduction mammoplasty and help improve the probability of obtaining prior authorization for insurance coverage. PMID- 26819652 TI - It is time to implement One Health approach to address health complex challenges! PMID- 26819653 TI - Draft genome sequence of Paenibacillus sp. strain A2. AB - Paenibacillus sp. strain A2 is a Gram-negative rod-shaped bacterium isolated from a mixture of formation water and petroleum in Daqing oilfield, China. This facultative aerobic bacterium was found to have a broad capacity for metabolizing hydrocarbon and organosulfur compounds, which are the main reasons for the interest in sequencing its genome. Here we describe the features of Paenibacillus sp. strain A2, together with the genome sequence and its annotation. The 7,650,246 bp long genome (1 chromosome but no plasmid) exhibits a G+C content of 54.2 % and contains 7575 protein-coding and 49 RNA genes, including 3 rRNA genes. One putative alkane monooxygenase, one putative alkanesulfonate monooxygenase, one putative alkanesulfonate transporter and four putative sulfate transporters were found in the draft genome. PMID- 26819654 TI - Erratum to: Complete genome sequences of Geobacillus sp. Y412MC52, a xylan degrading strain isolated from obsidian hot spring in Yellowstone National Park. AB - [This corrects the article DOI: 10.1186/s40793-015-0075-0.]. PMID- 26819655 TI - Hope and Disappointment: Covalent Inhibitors to Overcome Drug Resistance in Non Small Cell Lung Cancer. AB - In the last five years, the detailed understanding of how to overcome T790M drug resistance in non-small cell lung cancer (NSCLC) has culminated in the development of a third-generation of covalent EGFR inhibitors with excellent clinical outcomes. However, the emergence of a newly discovered acquired drug resistance challenges the concept of small molecule targeted cancer therapy in NSCLC. PMID- 26819656 TI - Academic-Industrial Collaboration: Toward the Consilience of Two Solitudes. AB - Current major advances in drug discovery can be traced back to pioneering contributions originating from academics over a century ago. Living in a symbiotic yet noninvasive coexistence, the academic community and the pharmaceutical industry have strived, each in their own way, to develop the modern medicines that benefit humankind today. The subject is presented from a historical and personal perspective. PMID- 26819657 TI - Cyclopropanamine Compounds and Use Thereof. PMID- 26819658 TI - Sulfonamide Derivatives and Pharmaceutical Applications Thereof. PMID- 26819651 TI - BMP signaling in mesenchymal stem cell differentiation and bone formation. AB - Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily and have diverse functions during development and organogenesis. BMPs play a major role in skeletal development and bone formation, and disruptions in BMP signaling cause a variety of skeletal and extraskeletal anomalies. Several knockout models have provided insight into the mechanisms responsible for these phenotypes. Proper bone formation requires the differentiation of osteoblasts from mesenchymal stem cell (MSC) precursors, a process mediated in part by BMP signaling. Multiple BMPs, including BMP2, BMP6, BMP7 and BMP9, promote osteoblastic differentiation of MSCs both in vitro and in vivo. BMP9 is one of the most osteogenic BMPs yet is a poorly characterized member of the BMP family. Several studies demonstrate that the mechanisms controlling BMP9-mediated osteogenesis differ from other osteogenic BMPs, but little is known about these specific mechanisms. Several pathways critical to BMP9-mediated osteogenesis are also important in the differentiation of other cell lineages, including adipocytes and chondrocytes. BMP9 has also demonstrated translational promise in spinal fusion and bone fracture repair. This review will summarize our current knowledge of BMP-mediated osteogenesis, with a focus on BMP9, by presenting recently completed work which may help us to further elucidate these pathways. PMID- 26819659 TI - Synthesis and Evaluation of 2,6-Modified Purine 2'-C-Methyl Ribonucleosides as Inhibitors of HCV Replication. AB - A variety of 2,6-modified purine 2'-C-methylribonucleosides and their phosphoramidate prodrugs were synthesized and evaluated for inhibition of HCV RNA replication in Huh-7 cells and for cytotoxicity in various cell lines. Cellular pharmacology and HCV polymerase incorporation studies on the most potent and selective compound are reported. PMID- 26819661 TI - Role of a Preorganized Scaffold Presenting Four Residues of a GM-3 Lactone Mimetic on Melanoma Progression. AB - Two tetravalent architectures, the glycocalix 7 and the RAFT 9, presenting four residues of a GM-3 ganglioside lactone mimetic, target the host compartment of melanoma and significantly abrogate the effect induced by cancer-associated fibroblasts (CAFs) contact + hypoxia in the motility and invasiveness of tumor cells. The data reported support the involvement of glycosphingolipids (GSLs) in hypoxia and show an interesting role played by compound 9 in targeting melanoma cells thereby interfering with melanoma progression. The unprecedented findings reported for the glycocluster 9 may contribute to the understanding of the critical and complex interactions between tumor cells and their local environment paving the way for new therapeutic agents. PMID- 26819660 TI - SAR Exploration Guided by LE and Fsp(3): Discovery of a Selective and Orally Efficacious RORgamma Inhibitor. AB - A novel series of RORgamma inhibitors was identified starting with the HTS hit 1. After SAR investigation based on a prospective consideration of two drug-likeness metrics, ligand efficiency (LE) and fraction of sp(3) carbon atoms (Fsp(3)), significant improvement of metabolic stability as well as reduction of CYP inhibition was observed, which finally led to discovery of a selective and orally efficacious RORgamma inhibitor 3z. PMID- 26819662 TI - Potent, Selective, and CNS-Penetrant Tetrasubstituted Cyclopropane Class IIa Histone Deacetylase (HDAC) Inhibitors. AB - Potent and selective class IIa HDAC tetrasubstituted cyclopropane hydroxamic acid inhibitors were identified with high oral bioavailability that exhibited good brain and muscle exposure. Compound 14 displayed suitable properties for assessment of the impact of class IIa HDAC catalytic site inhibition in preclinical disease models. PMID- 26819663 TI - Discovery of the Selective CYP17A1 Lyase Inhibitor BMS-351 for the Treatment of Prostate Cancer. AB - Efforts to identify a potent, reversible, nonsteroidal CYP17A1 lyase inhibitor with good selectivity over CYP17A1 hydroxylase and CYPs 11B1 and 21A2 for the treatment of castration-resistant prostate cancer (CRPC) culminated in the discovery of BMS-351 (compound 18), a pyridyl biaryl benzimidazole with an excellent in vivo profile. Biological evaluation of BMS-351 at a dose of 1.5 mg in castrated cynomolgus monkeys revealed a remarkable reduction in testosterone levels with minimal glucocorticoid and mineralcorticoid perturbation. Based on a favorable profile, BMS-351 was selected as a candidate for further preclinical evaluation. PMID- 26819664 TI - iPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections. AB - The Amaryllidaceae alkaloid trans-dihydrolycoricidine 7 and three analogues 8-10 were produced via asymmetric chemical synthesis. Alkaloid 7 proved superior to acyclovir, the current standard for herpes simplex virus, type 1 (HSV-1) infection. Compound 7 potently inhibited lytic HSV-1 infection, significantly reduced HSV-1 reactivation, and more potently inhibited varicella zoster virus (VZV) lytic infection. A configurationally defined (3R)-secondary alcohol at C3 proved crucial for efficacious inhibition of lytic HSV-1 infection. PMID- 26819665 TI - Discovery of a Potent and Orally Efficacious TGR5 Receptor Agonist. AB - TGR5 is a G protein-coupled receptor (GPCR), activation of which promotes secretion of glucagon-like peptide-1 (GLP-1) and modulates insulin secretion. The 2-thio-imidazole derivative 6g was identified as a novel, potent, and selective TGR5 agonist (hTGR5 EC50 = 57 pM, mTGR5 = 62 pM) with a favorable pharmacokinetic profile. The compound 6g was found to have potent glucose lowering effects in vivo during an oral glucose tolerance test in DIO C57 mice with ED50 of 7.9 mg/kg and ED90 of 29.2 mg/kg. PMID- 26819666 TI - Monoamine Oxidase Inhibitory Activity of Novel Pyrazoline Analogues: Curcumin Based Design and Synthesis. AB - A series of new 2-methoxy-4-(5-phenyl-4,5-dihydro-1H-pyrazol-3 yl)phenolderivatives, 4-13, were synthesized and tested for their human MAO inhibitory activity. All the compounds were found to be selective and reversible toward hMAO-A except 4, a selective inhibitor of hMAO-B and 12, a nonselective inhibitor. Compound 7 was found to be a potent inhibitor of hMAO-A with Ki = 0.06 +/- 0.003 MUM and was having selectivity index of (SI = 1.02 * 10(-5)). It was found to be better than standard drug, Moclobemide (hMAO-A with Ki = 0.11 +/- 0.01 MUM) with selectivity index of SI = 0.049. Molecular docking simulation was carried out to understand the crucial interactions responsible for selectivity and potency. PMID- 26819667 TI - A New Highly Reactive and Low Lipophilicity Fluorine-18 Labeled Tetrazine Derivative for Pretargeted PET Imaging. AB - A new (18)F-labeled tetrazine derivative was developed aiming at optimal radiochemistry, fast reaction kinetics in inverse electron-demand Diels-Alder cycloaddition (IEDDA), and favorable pharmacokinetics for in vivo bioorthogonal chemistry. The radiolabeling of the tetrazine was achieved in high yield, purity, and specific activity under mild reaction conditions via conjugation with 5 [(18)F]fluoro-5-deoxyribose, providing a glycosylated tetrazine derivative with low lipophilicity. The (18)F-tetrazine showed fast reaction kinetics toward the most commonly used dienophiles in IEDDA reactions. It exhibited excellent chemical and enzymatic stability in mouse plasma and in phosphate-buffered saline (pH 7.41). Biodistribution in mice revealed favorable pharmacokinetics with major elimination via urinary excretion. The results indicate that the glycosylated (18)F-labeled tetrazine is an excellent candidate for in vivo bioorthogonal chemistry applications in pretargeted PET imaging approaches. PMID- 26819668 TI - Development of Noviomimetics as C-Terminal Hsp90 Inhibitors. AB - KU-32 and KU-596 are novobiocin-derived, C-terminal heat shock protein 90 (Hsp90) modulators that induce Hsp70 levels and manifest neuroprotective activity. However, the synthetically complex noviose sugar requires 10 steps to prepare, which makes translational development difficult. In this study, we developed a series of "noviomimetic" analogues of KU-596, which contain noviose surrogates that can be easily prepared, while maintaining the ability to induce Hsp70 levels. Both sugar and sugar analogues were designed, synthesized, and evaluated in a luciferase reporter assay, which identified compound 37, a benzyl containing noviomimetic, as the most potent inducer of Hsp70. PMID- 26819669 TI - Potent, Selective, and Orally Bioavailable Inhibitors of VPS34 Provide Chemical Tools to Modulate Autophagy in Vivo. AB - Autophagy is a dynamic process that regulates lysosomal-dependent degradation of cellular components. Until recently the study of autophagy has been hampered by the lack of reliable pharmacological tools, but selective inhibitors are now available to modulate the PI 3-kinase VPS34, which is required for autophagy. Here we describe the discovery of potent and selective VPS34 inhibitors, their pharmacokinetic (PK) properties, and ability to inhibit autophagy in cellular and mouse models. PMID- 26819670 TI - Synthesis and Evaluation of Oxyguanidine Analogues of the Cysteine Protease Inhibitor WRR-483 against Cruzain. AB - A series of oxyguanidine analogues of the cysteine protease inhibitor WRR-483 were synthesized and evaluated against cruzain, the major cysteine protease of the protozoan parasite Trypanosoma cruzi. Kinetic analyses of these analogues indicated that they have comparable potency to previously prepared vinyl sulfone cruzain inhibitors. Co-crystal structures of the oxyguanidine analogues WRR-666 (4) and WRR-669 (7) bound to cruzain demonstrated different binding interactions with the cysteine protease, depending on the aryl moiety of the P1' inhibitor subunit. Specifically, these data demonstrate that WRR-669 is bound noncovalently in the crystal structure. This represents a rare example of noncovalent inhibition of a cysteine protease by a vinyl sulfone inhibitor. PMID- 26819671 TI - Optimizing Ligand Efficiency of Selective Androgen Receptor Modulators (SARMs). AB - A series of selective androgen receptor modulators (SARMs) containing the 1 (trifluoromethyl)benzyl alcohol core have been optimized for androgen receptor (AR) potency and drug-like properties. We have taken advantage of the lipophilic ligand efficiency (LLE) parameter as a guide to interpret the effect of structural changes on AR activity. Over the course of optimization efforts the LLE increased over 3 log units leading to a SARM 43 with nanomolar potency, good aqueous kinetic solubility (>700 MUM), and high oral bioavailability in rats (83%). PMID- 26819672 TI - Probabilistic Approach to Generating MPOs and Its Application as a Scoring Function for CNS Drugs. AB - Multiparameter optimization (MPO) scoring functions are popular tools for providing guidance on how to design desired molecules in medicinal chemistry. The utility of a new probabilistic MPO (pMPO) scoring function method and its application as a scoring function for CNS drugs are described in this letter. In this new approach, a minimal number of statistically determined empirical boundaries is combined with the probability distribution of the desired molecules to define desirability functions. This approach attempts to minimize the number of parameters that define MPO scores while maintaining a high level of predictive power. Results obtained from a test-set of orally approved drugs show that the pMPO approach described here can be used to separate desired molecules from undesired ones with accuracy comparable to a Bayesian model with the advantage of better human interpretability. The application of this pMPO approach for blood brain barrier penetrant drugs is also described. PMID- 26819673 TI - Tetrahydroisoquinoline Phenols: Selective Estrogen Receptor Downregulator Antagonists with Oral Bioavailability in Rat. AB - A series of tetrahydroisoquinoline phenols was modified to give an estrogen receptor downregulator-antagonist profile. Optimization around the core, alkyl side chain, and pendant aryl ring resulted in compounds with subnanomolar levels of potency. The phenol functionality was shown to be required to achieve highly potent compounds, but unusually this was compatible with obtaining high oral bioavailabilities in rat. PMID- 26819674 TI - Pyridones as Highly Selective, Noncovalent Inhibitors of T790M Double Mutants of EGFR. AB - The rapid advancement of a series of noncovalent inhibitors of T790M mutants of EGFR is discussed. The optimization of pyridone 1, a nonselective high-throughput screening hit, to potent molecules with high levels of selectivity over wtEGFR and the broader kinome is described herein. PMID- 26819675 TI - Potent Small Agonists of Protease Activated Receptor 2. AB - Many proteases cut the PAR2 N-terminus resulting in conformational changes that activate cells. Synthetic peptides corresponding to newly exposed N-terminal sequences of PAR2 also activate the receptor at micromolar concentrations. PAR2 selective small molecules reported here induce PAR2-mediated intracellular calcium signaling at nanomolar concentrations (EC50 = 15-100 nM, iCa(2+), CHO hPAR2 cells). These are the most potent and efficient small molecule ligands to activate PAR2-mediated calcium release and chemotaxis, including for human breast and prostate cancer cells. PMID- 26819676 TI - Discovery of MK-8831, A Novel Spiro-Proline Macrocycle as a Pan-Genotypic HCV NS3/4a Protease Inhibitor. AB - We have been focused on identifying a structurally different next generation inhibitor to MK-5172 (our Ns3/4a protease inhibitor currently under regulatory review), which would achieve superior pangenotypic activity with acceptable safety and pharmacokinetic profile. These efforts have led to the discovery of a novel class of HCV NS3/4a protease inhibitors containing a unique spirocyclic proline structural motif. The design strategy involved a molecular-modeling based approach, and the optimization efforts on the series to obtain pan-genotypic coverage with good exposures on oral dosing. One of the key elements in this effort was the spirocyclization of the P2 quinoline group, which rigidified and constrained the binding conformation to provide a novel core. A second focus of the team was also to improve the activity against genotype 3a and the key mutant variants of genotype 1b. The rational application of structural chemistry with molecular modeling guided the design and optimization of the structure-activity relationships have resulted in the identification of the clinical candidate MK 8831 with excellent pan-genotypic activity and safety profile. PMID- 26819678 TI - Pyrrolidinones as Modulators of Neurogenesis. PMID- 26819677 TI - Anti-Staphylococcal Biofilm Effects of Human Cathelicidin Peptides. AB - Staphylococcus aureus can live together in the form of biofilms to avoid elimination by the host. Thus, a useful strategy to counteract bacterial biofilms is to re-engineer human antimicrobial peptide LL-37 so that it can be used as a remedy for preventing and removing biofilms. This study reports antibiofilm effects of four human cathelicidin LL-37 peptides against community-associated and hospital isolated methicillin-resistant Staphylococcus aureus (MRSA) strains. Although the intact molecule LL-37 inhibited biofilm formation at low concentrations, it did not inhibit bacterial attachment nor disrupt preformed biofilms. However, two 17-residue peptides, GF-17 and 17BIPHE2, inhibited bacterial attachment, biofilm growth, and disrupted established biofilms. An inactive peptide RI-10 was used as a negative control. Our results obtained using the S. aureus mutants in a static biofilm model are consistent with the literature obtained in a flow cell biofilm model. Because 17BIPHE2 is the most effective biofilm disruptor with desired stability to proteases, it is a promising lead for developing new anti-MRSA biofilm agents. PMID- 26819679 TI - Differential Expression of MicroRNAs in Tissues and Plasma Co-exists as a Biomarker for Pancreatic Cancer. AB - OBJECTIVE: Pancreatic cancer (PC) is a lethal disease with disappointing results from current treatment modalities, suggesting that novel therapeutic strategies are urgently needed. Since microRNAs (miRNAs) are important player in biology, the clinical utility of miRNAs for designing novel therapeutics is an active area of research. The objective of the present study was to examine differentially expressed miRNAs between normal and tumor tissues, and in plasma samples obtained from PC patients, chronic pancreatitis (CP) patients and healthy subjects (HC). MATERIAL AND METHODS: The miRNA expression profiling using formalin-fixed paraffin embedded (FFPE) tissues from normal and tumor specimens was accomplished using miRBase version 19 (LC Sciences, Houston, TX, USA). Quantitative real-time PCR (qRT-PCR) was subsequently performed in individual samples for 7 selected miRNAs. In addition, qRT-PCR was also performed for assessing the expression of 8 selected miRNAs in plasma samples. RESULTS: A significant difference in the expressions of miR-21, miR-205, miR-155, miR-31, miR-203, miR-214 and miR-129-2 were found in tumor tissue samples. Lower expression of miR-214 was found to be associated with better overall survival. We also observed differential expression of 8 miRNAs in plasma samples of CP and PC patients compared to HC. Interestingly, over expression of miR-21, and miR-31 was noted in both tumor tissues and in the plasma. CONCLUSION: We found deregulated expression of miRNAs that could distinguish normal from PC in two different types of samples (tissues and plasma). Interestingly, lower expression of miR-214 was found to be associated with better overall survival. Although not statistically significant, we also observed higher expression of let-7a and lower expression of miR-508 to be associated with overall better survival. We conclude that our study nicely lays the foundation for detailed future investigations for assessing the role of these miRNAs in the pathology of pancreatic cancer. PMID- 26819680 TI - miR-203 Functions as a Tumor Suppressor by Inhibiting Epithelial to Mesenchymal Transition in Ovarian Cancer. AB - OBJECTIVE: Ovarian cancer is a gynecological malignancy that has a high mortality rate in women due to metastatic progression and recurrence. miRNAs are small, endogenous, noncoding RNAs that function as tumor suppressors or oncogenes in various human cancers by selectively suppressing the expression of target genes. The objective of this study is to investigate the role of miR-203 in ovarian cancer. METHODS: miR-203 was expressed in ovarian cancer SKOV3 and OVCAR3 cells using lentiviral vector and cell proliferation, migration, invasion were examined using MTT, transwell and Matrigel assays, respectively. Tumor growth was examined using Xenograft mouse model. RESULTS: miR-203 expression was downregulated, whereas expression of its target gene Snai2 was upregulated in human ovarian serous carcinoma tissue as compared to normal ovaries. In addition, high miR-203 expression was associated with long-term survival rate of ovarian cancer patients. miR-203 overexpression inhibited cell proliferation, migration, and invasion of SKOV3 and OVCAR3 ovarian cancer cells. Furthermore, miR-203 overexpression inhibited the epithelial to mesenchymal transition (EMT) in ovarian cancer cells. Silencing Snai2 with lentiviral short hairpin (sh) RNA mimics miR-203-mediated inhibition of EMT and tumor cell invasion. Xenografts of miR-203-overexpressing ovarian cancer cells in immunodeficient mice exhibited a significantly reduced tumor growth. CONCLUSION: miR-203 functions as a tumor suppressor by down regulating Snai2 in ovarian cancer. PMID- 26819681 TI - Comparative Analysis of Differentially Expressed miRNAs and their Downstream mRNAs in Ovarian Cancer and its Associated Endometriosis. AB - OBJECTIVE: There is an increased risk of developing ovarian cancer (OC) in patients with endometriosis. Hence, development of new biomarkers may provide a positive clinical outcome for early detection. MicroRNAs (miRNAs) are small non coding RNAs that play an important role in biological and pathological process and are currently used as diagnostic and prognostic markers in various cancers. In the current study, we assessed the differential expression of miRNAs from 19 paired ovarian cancer and its associated endometriosis tissue samples. In addition we also analyzed the downstream targets of those miRNAs. METHODS: Nineteen paired cases of ovarian cancer and endometriosis foci were identified by a gynecologic pathologist and macro-dissected. The total RNAs were extracted and subjected to comprehensive miRNA profiling from the pooled samples of these two different entities using microarray analysis. Later, the abnormal expressions of few selected miRNAs were validated in individual cases by quantitative real-time PCR (qRT-PCR). Ingenuity pathway analysis revealed target mRNAs which were validated by qRT-PCR. RESULTS: The miRNA profiling identified deregulation of greater than 1156 miRNAs in OC, of which the top seven were further validated by qRT-PCR. The expression of miR-1, miR-133a, and miR-451 were reduced significantly (p<0.0001) in the OC patients compared to its associated endometriosis. In contrast, the expression of miR-141, miR-200a, miR-200c, and miR-3613 were elevated significantly (p<0.05) in most of the OC patients. Furthermore, among the downstream mRNAs of these miRNAs, the level of PTEN expression was significantly (p<0.05) reduced in OC compared to endometriosis while no significant difference was observed in NF-kappaB expression. CONCLUSION: The expression of miRNAs and mRNAs in OC were significantly different compared to its concurrent endometriosis. These differential expressed miRNAs may serve as potential diagnostic and prognostic biomarkers for OC associated with endometriosis. PMID- 26819682 TI - Morphological Assessment of Cadaveric Radial, Brachial and Subclavian Arteries: A Neurointerventional Approach. AB - OBJECTIVE: The transradial catheterization (TRC) is becoming widespread, primarily for neurointerventions. Therefore, the evaluation of radial artery puncture in clinical practice and a better understanding of the anatomy are important to improve the safety of neuroendovascular surgery. METHODS: Ten formalin-fixed adult Korean cadavers were dissected to expose radial artery (RA), brachial artery (BrA) and subclvian artery (ScA), bilaterally. Vessel lengths and diameters were meaured using a caliper and distance between the specific point of vessels and the anatomical landmarks including the radial styloid process, the medial epicondyle of the humerus, the sternoclavicular joint, and the vertebral artery orifice were also measured. RESULTS: The average length between the radial (RAPS) and the BrA puncture sites (BrAPS) and between the vertebral artery orifice (VAO) and the BrA bifurcation (BrAB) did not differ between sides (p>0.05). The average length between the radial styloid process (RSP) and the RAPS was 13.41+/-2.19 mm, and the RSP was 26.85+/-2.47 mm from the median nerve (MN). The mean length between the medial epicondyle (ME) and the BrAPS as 44.23+/ 5.47 mm, whereas the distance between the ME and the MN was 42.23+/-4.77 mm. The average VAO-ScA angle was 70.94+/-6.12 degrees , and the length between the ScA junction (SCJ) and the VAO was 60.30+/-8.48 mm. CONCLUSION: This study provides basic anatomical information about the radial artery and the brachial route and can help improving new techniques, selection of size and shape of catheters for TRC. This can help neurointerventionists who adopt a transradial neuroendovascular approach and offers comprehensive and safe care to their patients. PMID- 26819683 TI - Histopathological Effects of Tissue Adhesives on Experimental Peripheral Nerve Transection Model in Rats. AB - OBJECTIVE: Our aim was to evaluate the histopathological effects of tissue adhesives on peripheral nerve regeneration after experimental sciatic nerve transection in rats and to search whether these tissue adhesives may possess a therapeutic potential in peripheral nerve injuries. METHODS: This experimental study was performed using 42 female Wistar-Albino rats distributed in 6 groups subsequent to transection of right sciatic nerves. Group I underwent external circumferential neurolysis; Group II received suture repair; Group III had local polymeric hydrogel based tissue adhesive administration; Group IV received suture repair and polymeric hydrogel based tissue adhesive application together; Group V had gelatin based tissue adhesive application and Group VI had suture repair and gelatin based tissue adhesive together. After a 6-week follow-up period, biopsies were obtained from site of neural injury and groups were compared with respect to histopathological scoring based on inflammatory, degenerative, necrotic and fibrotic changes. RESULTS: There were remarkable differences between control group and study groups with respect to inflammation (p=0.001), degeneration (p=0.002), necrosis (p=0.007), fibrosis (p<0.001) and vascularity (p=0.001). Histopathological scores were similar between study groups and the only noteworthy difference was that Group V displayed a lower score for necrosis and higher score in terms of vascularization. CONCLUSION: Our results imply that tissue adhesives can be useful in repair of peripheral nerve injuries by decreasing the surgical trauma and shortening the duration of intervention. Results with gelatin based tissue adhesive are especially promising since more intense vascularity was observed in tissue after application. However, trials on larger series with longer durations of follow-up are essential for reaching more reliable conclusions. PMID- 26819684 TI - Neuroprotective Effect of Resveratrol on Acute Brain Ischemia Reperfusion Injury by Measuring Annexin V, p53, Bcl-2 Levels in Rats. AB - BACKGROUND: Cerebral ischemia is as a result of insufficient cerebral blood flow for cerebral metabolic functions. Resveratrol is a natural phytoalexin that can be extracted from grape's skin and had potent role in treating the cerebral ischemia. Apoptosis, a genetically programmed cellular event which occurs after ischemia and leads to biochemical and morphological changes in cells. There are some useful markers for apoptosis like Bcl-2, bax, and p53. The last reports, researchers verify the apoptosis with early markers like Annexin V. METHODS: We preferred in this experimental study a model of global cerebral infarction which was induced by bilateral common carotid artery occlusion method. Rats were randomly divided into 4 groups : sham, ischemia-reperfusion (I/R), I/R plus 20 mg/kg resveratrol and I/R plus 40 mg/kg resveratrol. Statistical analysis was performed using Sigmastat 3.5 ve IBM SPSS Statistics 20. We considered a result significant when p<0.001. RESULTS: After administration of resveratrol, Bcl-2 and Annexin levels were significantly increased (p<0.001). Depending on the dose of resveratrol, Bcl2 levels increased, p53 levels decreased but Annexin V did not effected. P53 levels were significantly increased in ishemia group, so apoptosis is higher compared to other groups. CONCLUSION: In the acute period, Annexin V levels misleading us because the apoptotic cell counts could not reach a certain level. Therefore we should support our results with bcl-2 and p53. PMID- 26819685 TI - Endoscopic Fluorescence Angiography with Indocyanine Green : A Preclinical Study in the Swine. AB - OBJECTIVE: Microscopic indocyanine green (ICG) angiography is useful for identifying the completeness of aneurysm clipping and the preservation of parent arteries and small perforators. Neuroendoscopy is helpful for visualizing structures beyond the straight line of the microscopic view. We evaluated our prototype of endoscopic ICG fluorescence angiography in swine, which we developed in order to combine the merits of microscopic ICG angiography and endoscopy. METHODS: Our endoscopic ICG system consists of a camera, a light source, a display and software. This system can simultaneously display real-time visible and near infrared fluorescence imaging on the same monitor. A commercially available endoscope was used, which was 4 mm in diameter and had an angle of 30 degrees . A male crossbred swine was used. RESULTS: Under general anesthesia, a small craniotomy was performed and the brain surface of the swine was exposed. ICG was injected via the ear vein with a bolus dose of 0.3 mg/kg. Visible and ICG fluorescence images of cortical vessels were simultaneously observed on the display monitor at high resolution. The real-time merging of the visible and fluorescent images corresponded well. CONCLUSION: Simultaneous visible color and ICG fluorescent imaging of the cortical vessels in the swine brain was satisfactory. Technical improvement and clinical implication are expected. PMID- 26819686 TI - Surgical Flow Alteration for the Treatment of Intracranial Aneurysms That Are Unclippable, Untrappable, and Uncoilable. AB - OBJECTIVE: The treatment of complex intracranial aneurysms remains challenging. One approach is the application of surgical flow alteration to treat aneurysms that are neither clippable, trappable, or coilable. The efficacy and limitations of surgical flow alteration have not yet been established. METHODS: Cases of complex aneurysms treated with surgical flow alteration (proximal occlusion with or without bypass, distal occlusion with or without bypass and bypass only) were included in this retrospective study. RESULTS: Among a total of 16 cases, there were 7 giant aneurysms (>=25 mm diameter) and 9 large aneurysms (>10 mm diameter); 15 of 16 aneurysms were unruptured. There were 8 aneurysms located in the anterior circulation, while the other 8 were in the posterior circulation. Aneurysms were treated with proximal occlusion in 10 cases and distal occlusion in 5 cases; in 1 case, the aneurysm occluded spontaneously after bypass without parent artery occlusion. All but 2 cases underwent prior or concurrent bypass surgery. Complete obliteration of the aneurysm at the latest imaging follow-up was shown in 12 of 16 cases (75.0%). Bypass patency was confirmed in 13 of 15 cases (86.7%). Surgery-related morbidity developed in 3 cases (18.8%, Glasgow outcome scale of 4) and all were perforator infarctions. There were no mortalities. CONCLUSION: Surgical flow alteration resulted in a high rate of aneurysmal obliteration with acceptable morbidity. Although several limitations remained, it could represent an alternative method for treating complex aneurysms. PMID- 26819687 TI - Anatomical Variant of Atlas : Arcuate Foramen, Occpitalization of Atlas, and Defect of Posterior Arch of Atlas. AB - OBJECTIVE: We sought to examine anatomic variations of the atlas and the clinical significance of these variations. METHODS: We retrospectively reviewed 1029 cervical 3-dimensional (3D) CT images. Cervical 3D CT was performed between November 2011 and August 2014. Arcuate foramina were classified as partial or complete and left and/or right. Occipitalization of the atlas was classified in accordance with criteria specified by Mudaliar et al. Posterior arch defects of the atlas were classified in accordance with criteria specified by Currarino et al. RESULTS: One hundred and eight vertebrae (108/1029, 10.5%) showed an arcuate foramen. Bilateral arcuate foramina were present in 41 of these vertebrae and the remaining 67 arcuate foramina were unilateral (right 31, left 36). Right-side arcuate foramina were partial on 18 sides and complete on 54 sides. Left-side arcuate foramina were partial on 24 sides and complete on 53 sides. One case of atlas assimilation was found. Twelve patients (12/1029, 1.17%) had a defect of the atlantal posterior arch. Nine of these patients (9/1029, 0.87%) had a type A posterior arch defect. We also identified one type B, one type D, and one type E defect. CONCLUSION: Preoperative diagnosis of occipitalization of the atlas and arcuate foramina using 3D CT is of paramount importance in avoiding neurovascular injury during surgery. It is important to be aware of posterior arch defects of the atlas because they may be misdiagnosed as a fracture. PMID- 26819688 TI - Usefulness of Simple Rod Rotation to Correct Curve of Adolescent Idiopathic Scoliosis. AB - OBJECTIVE: To correct apical vertebral rotation for adolescent idiopathic scoliosis (AIS), direct vertebral derotation (DVD) or simple rod rotation (SRR) might be considered. The aim of the present study is to introduce the surgical experiences of AIS by a Korean neurosurgeon and to evaluate the effectiveness of SRR for apical vertebral rotation. METHODS: A total of 9 patients (1 male and 8 females) underwent scoliosis surgery by a neurosurgeon of our hospital. The Lenke classifications of the patients were 1 of 1B, 2 of 1C, 1 of 2A, 1 of 2C, 3 of 5C and 1 of 6C. Surgery was done by manner of simple rod rotation on the concave side and in situ coronal bending. Coronal Cobb's angles, vertebral rotation angles and SRS-22 were measured on a plain standing X-ray and CT before and after surgery. RESULTS: The mean follow up period was 25.7 months (range : 5-52). The mean number of screw positioning level was nine (6-12). The mean age was 16.4 years (range : 13-25) at surgery. The mean Risser grade was 3.7+/-0.9. The apical vertebral rotation measured from the CT scans was 25.8+/-8.5 degrees vs. 9.3+/ 6.7 degrees (p<0.001) and the Coronal Cobb's angle was 53.7+/-10.4 degrees vs. 15.4+/-6.5 degrees (p<0.001) preoperatively and postoperative, respectively. The SRS-22 improved from 71.9 preoperatively to 90.3 postoperatively. There were no complications related with the operations. CONCLUSION: SRR with pedicle screw instrumentation could be corrected successfully by axial rotation without complications. SRR might serve as a good option to correct AIS deformed curves of AIS. PMID- 26819689 TI - Learning Curve of Percutaneous Endoscopic Lumbar Discectomy Based on the Period (Early vs. Late) and Technique (in-and-out vs. in-and-out-and-in): A Retrospective Comparative Study. AB - OBJECTIVE: To report the learning curve of percutaneous endoscopic lumbar discectomy (PELD) for a surgeon who had not been previously exposed to this procedure based on the period and detailed technique with a retrospective matched comparative design. METHODS: Of 213 patients with lumbar disc herniation encountered during the reference period, 35 patients who were followed up for 1 year after PELD were enrolled in this study. The patients were categorized by the period and technique of operation : group A, the first 15 cases, who underwent by the 'in-and-out' technique; group B, the next 20 cases, who underwent by the 'in and-out-and-in' technique. The operation time, failure rate, blood loss, complication rate, re-herniation rate, the Visual Analogue Scale (VAS) for back and leg were checked. The alteration of dural sac cross-sectional area (DSCSA) between the preoperative and the postoperative MRI was checked. RESULTS: Operative time was rapidly reduced in the early phase, and then tapered to a steady state for the 35 cases receiving the PELD. After surgery, VAS scores for the back and leg were decreased significantly in both groups. Complications occurred in 2 patients in group A and 2 patients in group B. Between the two groups, there were significant differences in operative time, improvement of leg VAS, and expansion of DSCSA. CONCLUSION: PELD learning curve seems to be acceptable with sufficient preparation. However, because of their high tendency to delayed operation time, operation failure, and re-herniation, caution should be exercised at the early phase of the procedure. PMID- 26819690 TI - Acute Spontaneous Subdural Hematoma due to Rupture of a Tiny Cortical Arteriovenous Malformation. AB - Acute subdural hematoma (SDH) of arterial origin is rare, especially SDH associated with an arteriovenous malformation (AVM) is extremely rare. The authors report a case of acute spontaneous SDH due to rupture of a tiny cortical AVM. A 51-year-old male presented with sudden onset headache and mentality deterioration without a history of trauma. Brain CT revealed a large volume acute SDH compressing the right cerebral hemisphere with subfalcine and tentorial herniation. Emergency decompressive craniectomy was performed to remove the hematoma and during surgery a small (5 mm sized) conglomerated aciniform mass with two surrounding enlarged vessels was identified on the parietal cortex. After warm saline irrigation of the mass, active bleeding developed from a one of the vessel. The bleeding was stopped by coagulation and the vessels were removed. Histopathological examination confirmed the lesion as an AVM. We concluded that a small cortical AVM existed at this area, and that the cortical AVM had caused the acute SDH. Follow up conventional angiography confirmed the absence of remnant AVM or any other vascular abnormality. This report demonstrates rupture of a cortical AVM is worth considering when a patient presents with non-traumatic SDH without intracerebral hemorrhage or subarachnoid hemorrhage. PMID- 26819691 TI - Metastatic Brain Neuroendocrine Tumor Originating from the Liver. AB - A 67-year-old male presented with left temporal hemianopsia and left hemiparesis. A contrast-enhanced magnetic resonance image revealed a 4.5*3.5*5.0 cm rim enhancing mass with central necrosis and associated edema located in the left occipital lobe. Of positron emission tomography and abdominal computed tomography, a 9-cm mass with poor enhancement was found in the right hepatic lobe. Craniotomy and right hemihepatectomy was performed. The resected specimen showed histological features and immunochemical staining consistent with a metastatic neuroendocrine tumor (NET). Four months later, the tumors recurred in the brain, liverand spinal cord. Palliative chemotherapy with etoposide and cisplatin led to complete remission of recurred lesions, but the patient died for pneumonia. This is the first case of a metastatic brain NET originating from the liver. If the metastatic NET of brain is suspicious, investigation for primary lesion should be considered including liver. PMID- 26819692 TI - Primary Intracranial Leptomeningeal Melanomatosis. AB - Primary intracranial malignant melanoma is a very rare and highly aggressive tumor with poor prognosis. A 66-year-old female patient presented a headache that had been slowly progressing for several months. A large benign pigmented skin lesion was found on her back. A brain MRI showed multiple linear signal changes with branching pattern and strong enhancement in the temporal lobe. The cytological and immunohiostochemical cerebrospinal fluid examination confirmed malignant melanoma. A biopsy confirmed that the pigmented skin lesion on the back and the conjunctiva were benign nevi. We report a case of primary intracranial malignant melanoma and review relevant literatures. PMID- 26819693 TI - Isolated Supratentorial Intraventricular Recurrence of Medulloblastoma. AB - Medulloblastoma is a common pediatric tumor typically diagnosed before the age of fifteen. Initial therapy includes surgical resection and radiation of the entire neuro-axis. Recurrence is common and typically occurs within 2 years of initial diagnosis. Those fitting Collin's Law is considered tumor-free. We report a case of single supratentorial recurrence 13 years after initial diagnosis. Here we present a 22 year old male presenting 13 years after initial diagnosis with isolated septum pellucidum recurrence. He underwent complete resection of the tumor. Medulloblastoma is a common in the pediatric population. Late recurrence to the ventricular system is uncommon. Long term follow-up is recommended in these patients. PMID- 26819695 TI - Contralateral Juxtafacet Cyst Development after the Spontaneous Resolution of a Previous Facet Cyst. AB - Juxtafacet cysts are implicated in neural compression. Thus far, it is known that surgical removal is the definitive treatment for symptomatic juxtafacet cyst because spontaneous regression is rare, and the failure rate of conservative treatment is high. We have reported a rare case of right-sided juxtafacet cyst development after the spontaneous resolution of contralateral left-sided facet cyst. The left-sided facet cyst resolved spontaneously without surgical treatment, but a juxtacyst developed on the contralateral facet on the right side, as illustrated on 4-year follow-up magnetic resonance images. To the best of our knowledge, this is the first report of newly developed contralateral juxtafacet cyst after spontaneous regression. Herein, we have discussed the natural history and the management of this rare case. PMID- 26819694 TI - Lying Down Instability Undetected on Standing Dynamic Radiographs. AB - It is well known that spinal instability should be evaluated in the standing lateral position. Standing dynamic flexion and extension radiographs are usually used to assess spinal instability. Here, we report a patient who experienced distraction instability while in the supine position rather than the standard standing position. To our knowledge, this is the first report of lying-down instability undetected on standing dynamic flexion and extension radiographs. We discuss the pathophysiological mechanism of this uncommon but possible entity and provide a review of the literature. PMID- 26819696 TI - Atypical Intramuscular Myxoma of the Lumbosacral Paraspinal Muscle: The First Case Report in Asian. AB - Intramuscular myxoma (IM) is a benign neoplasm of mesenchymal origin. We report a rare case of IM which was located in the lumbosacral paraspinal muscles. A 62 year-old female patient presented with progressive low back pain for 2 months, and the radiologic findings showed a large mass (4.0*3.5*6.5 cm) in the right lumbosacral paraspinal area. Total resection of the tumor was performed and the symptom was nearly resolved after surgery. Although the immuno-histopathological analysis was consistent with IM, there were some different findings from typical pathological characteristics of IM in this case. Firstly, the symptomatic change of the mass took relatively short time (less than 3 months), and this change was accompanied by partial calcification inside the mass. Moreover, iatrogenic interruption of paravertebral muscle by the other previous operation might be the promoting factor of the fibrous dysplasia, which can explain the pathogenesis of IM. To our knowledge, this is the eighth case of the lumbar paraspinal myxoma reported in the literatures and the first case in Asian population. PMID- 26819697 TI - Use of an Ultrasonic Osteotome for Direct Removal of Beak-Type Ossification of Posterior Longitudinal Ligament in the Thoracic Spine. AB - Direct removal of beak-type ossification of posterior longitudinal ligament at thoracic spine (T-OPLL) is a challenging surgical technique due to the potential risk of neural injury. Slipping off the cutting surface of a high-speed drill may result in entrapment in neural structures, leading to serious complications. Removal of T-OPLL with an ultrasonic osteotome, utilizing back and forth micro motion of a blade rather than rotatory-motion of drill, may reduce such complications. We have applied the ultrasonic osteotome for posterior circumferential decompression of T-OPLL for three consecutive patients with beak type OPLL and have described the surgical techniques and patient outcomes. The preoperative chief complaint was gait disturbance in all patients. Japanese orthopedic association scores (JOA) was used for functional assessment. Scores measured 2/11, 5/11, 2/11, and 4/11 for each patient. The ventral T-OPLL mass was exposed after posterior midline approach, laminotomy and transeversectomy. The T OPLL mass was directly removed with an ultrasonic osteotome and instrumented segmental fixation was performed. The surgeries were uneventful. Detailed surgical techniques were presented. Gait disturbance was improved in all patients. Dural tear occurred in one patient without squeal. Postoperative JOA was 6/11, 10/11, 8/11, and 8/11 (recovery rate; 44%, 83%, 67%, and 43%) respectively at 18, 18, 10, and 1 months postoperative. T-OPLL was completely removed in all patients as confirmed with computed tomography scan. We hope that surgical difficulties in direct removal of T-OPLL might be reduced by utilizing ultrasonic osteotome. PMID- 26819698 TI - Free Hand Insertion Technique of S2 Sacral Alar-Iliac Screws for Spino-Pelvic Fixation: Technical Note, Acadaveric Study. AB - A rigid spino-pelvic fixation to anchor long constructs is crucial to maintain the stability of long fusion in spinal deformity surgery. Besides obtaining immediate stability and proper biomechanical strength of constructs, the S2 alar iliac (S2AI) screws have some more advantages. Four Korean fresh-frozen human cadavers were procured. Free hand S2AI screw placement is performed using anatomic landmarks. The starting point of the S2AI screw is located at the midpoint between the S1 and S2 foramen and 2 mm medial to the lateral sacral crest. Gearshift was advanced from the desired starting point toward the sacro iliac joint directing approximately 20 degrees angulation caudally in sagittal plane and 30 degrees angulation horizontally in the coronal plane connecting the posterior superior iliac spine (PSIS). We made a S2AI screw trajectory through the cancellous channel using the gearshift. We measured caudal angle in the sagittal plane and horizontal angle in the coronal plane. A total of eight S2AI screws were inserted in four cadavers. All screws inserted into the iliac crest were evaluated by C-arm and naked eye examination by two spine surgeons. Among 8 S2AI screws, all screws were accurately placed (100%). The average caudal angle in the sagittal plane was 17.3+/-5.4 degrees . The average horizontal angle in the coronal plane connecting the PSIS was 32.0+/-1.8 degrees . The placement of S2AI screws using the free hand technique without any radiographic guidance appears to an acceptable method of insertion without more radiation or time consuming. PMID- 26819699 TI - Altered gaze following during live interaction in infants at risk for autism: an eye tracking study. AB - BACKGROUND: The ability to follow gaze is an important prerequisite for joint attention, which is often compromised in children with autism spectrum disorder (ASD). The direction of both the head and eyes provides cues to other people's attention direction, but previous studies have not separated these factors and their relation to ASD susceptibility. Development of gaze following typically occurs before ASD diagnosis is possible, and studies of high-risk populations are therefore important. METHODS: Eye tracking was used to assess gaze following during interaction in a group of 10-month-old infants at high familial risk for ASD (high-risk group) as well as a group of infants with no family history of ASD (low-risk group). The infants watched an experimenter gaze at objects in the periphery. Performance was compared across two conditions: one in which the experimenter moved both the eyes and head toward the objects (Eyes and Head condition) and one that involved movement of the eyes only (Eyes Only condition). RESULTS: A group by condition interaction effect was found. Specifically, whereas gaze following accuracy was comparable across the two conditions in the low-risk group, infants in the high-risk group were more likely to follow gaze in the Eyes and Head condition than in the Eyes Only condition. CONCLUSIONS: In an ecologically valid social situation, responses to basic non-verbal orienting cues were found to be altered in infants at risk for ASD. The results indicate that infants at risk for ASD may rely disproportionally on information from the head when following gaze and point to the importance of separating information from the eyes and the head when studying social perception in ASD. PMID- 26819700 TI - Inhibiting Helicobacter pylori HtrA protease by addressing a computationally predicted allosteric ligand binding site. AB - Helicobacter pylori is associated with inflammatory diseases and can cause gastric cancer and mucosa-associated lymphoma. One of the bacterium's key proteins is high temperature requirement A (HpHtrA) protein, an extracellular serine protease that cleaves E-cadherin of gastric epithelial cells, which leads to loss of cell-cell adhesion. Inhibition of HpHtrA may constitute an intervention strategy against H. pylori infection. Guided by the computational prediction of hypothetical ligand binding sites on the surface of HpHtrA, we performed residue mutation experiments that confirmed the functional relevance of an allosteric region. We virtually screened for potential ligands addressing this surface cleft located between the catalytic and PDZ1 domains. Our receptor-based computational method represents protein surface pockets in terms of graph frameworks and retrieves small molecules that satisfy the constraints given by the pocket framework. A new chemical entity was identified that blocked E cadherin cleavage in vitro by direct binding to HpHtrA, and efficiently blocked pathogen transmigration across the gastric epithelial barrier. A preliminary crystal structure of HpHtrA confirms the validity of a comparative "homology" model of the enzyme, which we used for the computational study. The results of this study demonstrate that addressing orphan protein surface cavities of target macromolecules can lead to new bioactive ligands. PMID- 26819702 TI - miRNAs as potential biomarkers in early breast cancer detection following mammography. AB - Breast cancer is the most common cancer among American women, except for skin cancers. About 12 % women in the United States will develop invasive breast cancer during their lifetime. Currently one of the most accepted model/theories is that ductal breast cancer (most common type of breast cancer) follows a linear progression: from normal breast epithelial cells to ductal hyperplasia to atypical ductal hyperplasia (ADH) to ductal carcinoma in situ (DCIS), and finally to invasive ductal carcinoma (IDC). Distinguishing pure ADH diagnosis from DCIS and/or IDC on mammography, and even combined with follow-up core needle biopsy (CNB) is still a challenge. Therefore subsequent surgical excision cannot be avoided to make a definitive diagnosis. MicroRNAs (miRNAs) are a highly abundant class of endogenous non-coding RNAs, which contribute to cancer initiation and progression, and are differentially expressed between normal and cancer tissues. They can function as either tumor suppressors or oncogenes. With accumulating evidence of the role of miRNAs in breast cancer progression, including our own studies, we sought to summarize the nature of early breast lesions and the potential use of miRNA molecules as biomarkers in early breast cancer detection. In particular, miRNA biomarkers may potentially serve as a companion tool following mammography screening and CNB. In the long-term, a better understanding of the molecular mechanisms underlying the miRNA signatures associated with breast cancer development could potentially result in the development of novel strategies for disease prevention and therapy. PMID- 26819703 TI - Assessment of microsatellite and SNP markers for parentage assignment in ex situ African Penguin (Spheniscus demersus) populations. AB - Captive management of ex situ populations of endangered species is traditionally based on pedigree information derived from studbook data. However, molecular methods could provide a powerful set of complementary tools to verify studbook records and also contribute to improving the understanding of the genetic status of captive populations. Here, we compare the utility of single nucleotide polymorphisms (SNPs) and microsatellites (MS) and two analytical methods for assigning parentage in ten families of captive African penguins held in South African facilities. We found that SNPs performed better than microsatellites under both analytical frameworks, but a combination of all markers was most informative. A subset of combined SNP (n = 14) and MS loci (n = 10) provided robust assessments of parentage. Captive or supportive breeding programs will play an important role in future African penguin conservation efforts as a source of individuals for reintroduction. Cooperation among these captive facilities is essential to facilitate this process and improve management. This study provided us with a useful set of SNP and MS markers for parentage and relatedness testing among these captive populations. Further assessment of the utility of these markers over multiple (>3) generations and the incorporation of a larger variety of relationships among individuals (e.g., half-siblings or cousins) is strongly suggested. PMID- 26819701 TI - Profiling the Reactivity of Cyclic C-Nucleophiles towards Electrophilic Sulfur in Cysteine Sulfenic Acid. AB - Oxidation of a protein cysteine thiol to sulfenic acid, termed S-sulfenylation, is a reversible post-translational modification that plays a crucial role in regulating protein function and is correlated with disease states. The majority of reaction-based small molecule and immunochemical probes used for detecting sulfenic acids are based on the 5,5-dimethyl-1,3-cyclohexanedione (dimedone) scaffold, which is selective, but suffers from low reactivity. In addition, mechanistic details and features that diminish or enhance nucleophile reactivity remain largely unknown. A significant hurdle to resolving the aforementioned issues has been the chemically unstable nature of small-molecule sulfenic acid models. Herein, we report a facile mass spectrometry-based assay and repurposed dipeptide-based model to screen a library of cyclic C-nucleophiles for reactivity with sulfenic acid under aqueous conditions. Observed rate constants for ~100 cyclic C-nucleophiles were obtained and, from this collection, we have identified novel compounds with more than 200-fold enhanced reactivity, as compared to dimedone. The increase in reactivity and retention of selectivity of these C nucleophiles were validated in secondary assays, including a protein model for sulfenic acid. Together, this work represents a significant step toward developing new chemical reporters for detecting protein S-sulfenylation with superior kinetic resolution. The enhanced rates and varied composition of the C nucleophiles should enable more comprehensive analyses of the sulfenome and serve as the foundation for reversible or irreversible nucleophilic covalent inhibitors that target oxidized cysteine residues in therapeutically important proteins. PMID- 26819704 TI - Global pattern of phylogenetic species composition of shark and its conservation priority. AB - The diversity of marine communities is in striking contrast with the diversity of terrestrial communities. In all oceans, species richness is low in tropical areas and high at latitudes between 20 and 40 degrees . While species richness is a primary metric used in conservation and management strategies, it is important to take into account the complex phylogenetic patterns of species compositions within communities. We measured the phylogenetic skew and diversity of shark communities throughout the world. We found that shark communities in tropical seas were highly phylogenetically skewed, whereas temperate sea communities had phylogenetically diversified species compositions. Interestingly, although geographically distant from one another, tropical sea communities were all highly skewed toward requiem sharks (Carcharhinidae), hammerhead sharks (Sphyrnidae), and whale sharks (Rhincodon typus). Worldwide, the greatest phylogenetic evenness in terms of clades was found in the North Sea and coastal regions of countries in temperate zones, such as the United Kingdom, Ireland, southern Australia, and Chile. This study is the first to examine patterns of phylogenetic diversity of shark communities on a global scale. Our findings suggest that when establishing conservation activities, it is important to take full account of phylogenetic patterns of species composition and not solely use species richness as a target. Protecting areas of high phylogenetic diversity in sharks, which were identified in this study, could form a broader strategy for protecting other threatened marine species. PMID- 26819705 TI - Effects of dietary supplementation of probiotic, Clostridium butyricum, on growth performance, immune response, intestinal barrier function, and digestive enzyme activity in broiler chickens challenged with Escherichia coli K88. AB - BACKGROUND: Colibacillosis caused by enterotoxigenic Escherichia coli (E. coli) results in economic losses in the poultry industry. Antibiotics are usually used to control colibacillosis, however, E. coli has varying degrees of resistance to different antibiotics. Therefore the use of probiotics is becoming accepted as an alternative to antibiotics. In this study, we evaluated the effects of Clostridium butyricum (C. butyricum) on growth performance, immune response, intestinal barrier function, and digestive enzyme activity in broiler chickens challenged with Escherichia coli (E. coli) K88. METHODS: The chickens were randomly divided into four treatment groups for 28 days. Negative control treatment (NC) consisted of birds fed a basal diet without E. coli K88 challenge and positive control treatment (PC) consisted of birds fed a basal diet and challenged with E. coli K88. C. butyricum probiotic treatment (CB) consisted of birds fed a diet containing 2 * 10(7) cfu C. butyricum/kg of diet and challenged with E. coli K88. Colistin sulfate antibiotic treatment (CS) consisted of birds fed a diet containing 20 mg colistin sulfate/kg of diet and challenged with E. coli K88. RESULTS: The body weight (BW) and average day gain (ADG) in the broilers of CB group were higher (P < 0.05) than the broilers in the PC group overall except the ADG in the 14-21 d post-challenge. The birds in CB treatment had higher (P < 0.05) concentration of tumor necrosis factor-alpha (TNF-alpha) at 3 and 7 d post-challenge, and higher (P < 0.05) concentration of interleukin-4 (IL-4) at 14 d post-challenge than those in the PC treatment group. The concentration of serum endotoxin in CB birds was lower (P < 0.05) at 21 d post challenge, and the concentrations of serum diamine oxidase in CB birds were lower (P < 0.05) at 14 and 21 d post-challenge than in PC birds. Birds in CB treatment group had higher (P < 0.05) jejunum villi height than those in PC, NC, or CS treatment at 7, 14, and 21 d post-challenge. In comparison to PC birds, the CB birds had lower (P < 0.05) jejunum crypt depth during the whole experiment. The birds in CB or CS treatment group had higher (P < 0.05) activities of amylase and protease at 3, 7, and 14 d post-challenge, and higher (P < 0.05) activity of lipase at 3, 7 d post-challenge than PC birds. CONCLUSIONS: In all, these results indicate that dietary supplementation with C. butyricum promotes immune response, improves intestinal barrier function, and digestive enzyme activities in broiler chickens challenged with E. coli K88. There is no significant difference between the C. butyricum probiotic treatment and the colistin sulfate antibiotic treatment. Therefore, the C. butyricum probiotic may be an alternative to antibiotic for broiler chickens. PMID- 26819707 TI - Differential fall migratory routes of adult and juvenile Ipswich Sparrows (Passerculus sandwichensis princeps). AB - BACKGROUND: Island breeding birds present an ideal system for studying migratory movements in passerines because their populations are clearly demarcated, and individuals must depart on migration from a single location. The Ipswich Sparrow (Paserculus sandwichensis princeps) is a subspecies of the Savannah Sparrow that breeds exclusively on Sable Island, Nova Scotia, Canada and winters along the Atlantic coast of North America. We used a network of 34 automated VHF telemetry receivers to track radio-tagged adult and juvenile Ipswich Sparrows from their breeding island southward through the first half of their fall migratory journey. RESULTS: We compared adult to juvenile timing and routes. We show that juveniles leave the island approximately 24 days prior to adults and remain temporally separated from them during migration through Nova Scotia. Juveniles have different overwater orientations that result in migratory routes with shorter ocean crossings and a longer overall distance travelled compared to adults. Juveniles also have more frequent and longer stopovers, and displayed some reverse migration. CONCLUSION: We demonstrate that migratory routes differ between adults and juveniles, suggesting that routes change as individuals age, possibly through learning or social interactions. These differential routes also suggest that sparrows experience risk in different ways with juveniles selecting shorter overwater flights with less navigational risk at the cost of increased time spent in migration. PMID- 26819706 TI - Developmental changes in intercellular junctions and Kv channels in the intestine of piglets during the suckling and post-weaning periods. AB - BACKGROUND: The intestinal epithelium is an important barrier that depends on a complex mixture of proteins and these proteins comprise different intercellular junctions. The purpose of this study was to investigate the postnatal and developmental changes in morphology, intercellular junctions and voltage-gated potassium (Kv) channels in the intestine of piglets during the suckling and post weaning periods. RESULTS: Samples of the small intestine were obtained from 1-, 7 , 14-, and 21-d-old suckling piglets and piglets on d 1, 3, 5, and 7 after weaning at 14 d of age. The results showed that the percentage of proliferating cell nuclear antigen (PCNA)-positive cells and alkaline phosphatase (AKP) activity, as well as the abundances of E-cadherin, occludin, and Kv1.5 mRNA and claudin-1, claudin-3, and occludin protein in the jejunum were increased from d 1 to d 21 during the suckling period (P < 0.05). Weaning induced decreases in the percentage of PCNA-positive cells, AKP activity and the abundances of E-cadherin, occludin and zonula occludens (ZO)-1 mRNA or protein in the jejunum on d 1, 3 and 5 post-weaning (P < 0.05). There were lower abundances of E-cadherin, occludin and ZO-1 mRNA as well as claudin-1, claudin-3 and ZO-1 protein in the jejunum of weanling piglets than in 21-d-old suckling piglets (P < 0.05). The abundances of E-cadherin, occludin, ZO-1 and integrin mRNA were positively related to the percentage of PCNA-positive cells. CONCLUSION: Weaning at 14 d of age induced damage to the intestinal morphology and barrier. While there was an adaptive restoration on d 7 post-weaning, the measured values did not return to the pre weaning levels, which reflected the impairment of intercellular junctions and Kv channels. PMID- 26819709 TI - Sonocatalytic degradation of humic acid by N-doped TiO2 nano-particle in aqueous solution. AB - BACKGROUND: Un-doped and N-doped TiO2 nano-particles with different nitrogen contents were successfully synthesized by a simple sol-gel method, and were characterized by X-ray diffraction, field emission scanning electron microscopy, Energy dispersive X-ray analysis and UV-visible diffuse reflectance spectra techniques. Then enhancement of sonocatalytic degradation of humic acid by un doped and N-doped TiO2 nano-particles in aqueous environment was investigated. The effects of various parameters such as initial concentration of humic acid, N doping, and the degradation kinetics were investigated. RESULTS: The results of characterization techniques affirmed that the synthesis of un-doped and N-doped TiO2 nano-particles was successful. Degradation of humic acid by using different nano-particles obeyed the first-order kinetic. Among various nano-particles, N doped TiO2 with molar doping ratio of 6 % and band gap of 2.92 eV, exhibited the highest sonocatalytic degradation with an apparent-first-order rate constant of 1.56 * 10(-2) min(-1). CONCLUSIONS: The high degradation rate was associated with the lower band gap energy and well-formed anatase phase. The addition of nano catalysts could enhance the degradation efficiency of humic acid as well as N doped TiO2 with a molar ratio of 6 %N/Ti was found the best nano-catalyst among the investigated catalysts. The sonocatalytic degradation with nitrogen doped semiconductors could be a suitable oxidation process for removal of refractory pollutants such as humic acid from aqueous solution. PMID- 26819708 TI - Rationale, design, and profile of Comprehensive Registry of In-Hospital Intensive Care for OHCA Survival (CRITICAL) study in Osaka, Japan. AB - BACKGROUND: We established a multi-center, prospective cohort that could provide appropriate therapeutic strategies such as criteria for the introduction and the effectiveness of in-hospital advanced treatments, including percutaneous coronary intervention (PCI), target temperature management, and extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) patients. METHODS: In Osaka Prefecture, Japan, we registered all consecutive patients who were suffering from an OHCA for whom resuscitation was attempted and who were then transported to institutions participating in this registry since July 1, 2012. A total of 11 critical care medical centers and one hospital with an emergency care department participated in this registry. The primary outcome was neurological status after OHCA, defined as cerebral performance category (CPC) scale. RESULTS: A total of 688 OHCA patients were documented between July 2012 and December 2012. Of them, 657 were eligible for our analysis. Patients' average age was 66.2 years old, and male patients accounted for 66.2 %. The proportion of OHCAs having a cardiac origin was 50.4 %. The proportion as first documented rhythm of ventricular fibrillation/pulseless ventricular tachycardia was 11.6 %, pulseless electrical activity 23.4 %, and asystole 54.5 %. After hospital arrival, 10.5 % received defibrillation, 90.8 % tracheal intubation, 3.0 % ECPR, 3.5 % PCI, and 83.1 % adrenaline administration. The proportions of 90 day survival and CPC 1/2 at 90 days after OHCAs were 5.9 and 3.0 %, respectively. CONCLUSIONS: The Comprehensive Registry of In-hospital Intensive Care for OHCA Survival (CRITICAL) study will enroll over 2000 OHCA patients every year. It is still ongoing without a set termination date in order to provide valuable information regarding appropriate therapeutic strategies for OHCA patients (UMIN000007528). PMID- 26819710 TI - Interleukin 20 regulates dendritic cell migration and expression of co stimulatory molecules. AB - BACKGROUND: Psoriasis is an inflammatory disease characterized by leukocyte skin infiltration. Interestingly, recent works suggest that the migration of dendritic cells (DCs) is abnormal in psoriatic skin. DCs have significant role in regulating the function of T lymphocytes, at least in part influenced by the local environment of cytokines. In psoriatic skin lesions the expression of IL-20 is highly up-regulated. It is unclear if this cytokine has any influence on DCs. METHODS: Here, we investigated the influence of IL-20 in monocyte-derived dendritic cell (MDDCs) in vitro. This work addressed IL-20 effects on DC maturation, receptor expression and signaling. By use of extra cellular matrix components mimicking the skin environment, we also studied the functional effects of IL-20 on the chemotactic migration of DCs. Based on the recent finding that CD18 integrin are shed during migration of myeloid leukocytes, the concentration of these adhesion molecules was measured in MDDCs culture supernatants post migration. RESULTS: Following stimulation with IL-20, immature human MDDCs enhanced the expression of the co-stimulatory molecule CD86, further enabling activation of the p38 MAPK, but not the STAT3, pathway. IL-20 increased the migration of MDDCs in a biphasic response narrowly controlled by the interleukin concentration. A concomitant change in the shedding of CD18 integrins suggested that these adhesion molecules play a role in the migration of the MDDCs through the extracellular matrix layer. CONCLUSION: Taken together, our findings points to a possible, yet subtle, role of IL-20 in DCs migration. The biphasic response suggests that the aberrant IL-20 expression in psoriasis impedes DC migration, which could be a part of the processes that precipitates the dysregulated inflammatory response associated with this disease. PMID- 26819712 TI - Journal of pharmaceutical health care and sciences. PMID- 26819711 TI - Metabolic endotoxaemia in childhood obesity. AB - BACKGROUND: Childhood obesity is associated with chronic low-grade inflammation considered as a precursor to metabolic disease; however, the underlying mechanisms for this remain unclear. Studies in adults have implicated gut derived gram-negative bacterial fragments known as lipopolysaccharide or endotoxin, activating the inflammatory response, whilst the importance in childhood obesity is unclear. The aim of this research is to understand the relationship between circulating endotoxin in childhood obesity, and its' association with inflammatory and cardiovascular (CV) injury biomarkers. METHODS: Fasted blood was obtained from children with varying degrees of obesity (age: 13.9 +/- 2.3Yr; BMI: 35.1 +/- 5.2 Kg/m(2); n = 60). Multiplex CVD biomarker immunoassays were used to determine systemic levels of inflammatory and vascular injury biomarkers, such as tumour necrosis factor-alpha (TNF-alpha), interleukin (IL-) 1beta, 6, 8 and 10, plasminogen activator inhibitor-1 (PAI-1), soluble intercellular adhesion molecule type-1 (sICAM-1), matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO) and vascular endothelial growth factor (VEGF) as well as endotoxin levels. RESULTS: Endotoxin levels demonstrated a significant and positive correlation with the markers for inflammation, vascular injury and atherogenesis (TNF-alpha: r(2) = 0.077, p < 0.05; PAI-1: r(2) = 0.215, p < 0.01; sICAM-1: r(2) = 0.159, p < 0.01; MMP-9: r(2) = 0.159, p < 0.01; MPO: r(2) = 0.07, p < 0.05; VEGF: r(2) = 0.161, p < 0.01). Males demonstrated significantly higher circulating endotoxin than females (Males: 9.63 +/- 5.34 EU/ml; p = 0.004; Females: 5.56 +/- 4.06 EU/ml; n = 60) in these BMI and age-matched cohorts. CONCLUSION: The present study demonstrates for the first time a significant association between circulating endotoxin and biomarkers of metabolic risk in children as young as 11 years. Thus, endotoxin-mediated sub-clinical inflammation during childhood obesity may be a key contributor to T2DM and CVD development later in life. PMID- 26819713 TI - Pharmacist-managed clinics for patient education and counseling in Japan: current status and future perspectives. AB - To improve the adherence to and knowledge about pharmacotherapy in outpatients and to maximize the efficacy and minimize the adverse drug events, the first pharmacist-managed clinic (PMC) in Japan was established for anticoagulation therapy at Nagoya University Hospital in 2000. Since then, various PMCs such as for asthma/chronic obstructive pulmonary disease, Alzheimer's disease, hypercholesterolemia, chronic hepatitis C, cancer chemotherapy, palliative care, chronic kidney disease, and continuous ambulatory peritoneal dialysis have been established and expanded to many hospitals in Japan. Accumulating evidences suggest that PMCs have some beneficial effects on patients' adherence to and knowledge about their pharmacotherapy as well as the clinical outcome, besides being cost-effective. Notably, PMCs for cancer chemotherapy have been approved as a new medical service in hospitals in 2014, which is covered by the universal health coverage in Japan. In this review article, the current status of PMCs for patient education and counseling in Japan and their impact on pharmaceutical care and management are critically reviewed. Furthermore, future perspectives on PMCs are discussed. PMID- 26819714 TI - Expected value of the additional state in evaluating the method of quantification and uncertainty of additional states in an analytical model of grade I hypertension. AB - BACKGROUND: In the construction of pharmacoeoconomic models, simplicity is desirable for transparency (people can see how the model is built), ease of analysis, validation (how well the model reproduces reality), and description. Few reports have described concrete methods for constructing simpler models. Therefore we focused on the value of additional states and uncertainty in disease models with multiple complications. OBJECTIVES: The objective of this study was to examine the possibility of ranking additional states in disease models with multiple complications using a method for evaluating the quantification and uncertainty of additional states. METHODS: The expected value of additional states (EVAS) was formulated to calculate the value of additional states from the variation between analytic models using the net benefit method, and uncertainty was subtracted from the variation. We also verified the usefulness and availability of this method in grade I hypertension as a verification of the disease model. We assumed that stroke was recognized as an associated complication of hypertension in the basic model. In addition, stroke recurrence, coronary heart disease (CHD), and end-stage renal disease (ESRD) were assumed to represent other complications of hypertension. Ten thousand Monte Carlo simulations were performed, and the probability distribution was assumed to be the beta distribution in clinical parameters. The ranges of clinical parameters were +/-6.25%, 12.5%, 25%, and 50% of the standard deviation from the mean value. RESULTS: The EVAS in complications of CHD showed the greatest uncertainty. In contrast, the EVAS of ESRD differed from stroke recurrence in the value ranking by uncertainty. CONCLUSIONS: The EVAS has the potential to determine the ranking of additional states based on the quantitative value and uncertainty in disease models with multiple complications. PMID- 26819715 TI - Clinical risk factors associated with postoperative delirium and evaluation of delirium management and assessment team in lung and esophageal cancer patients. AB - BACKGROUND: Delirium is an acute change in cognition and concentration that complicates the postoperative course. Patients who suffer delirium after surgery have an increased risk of persistent cognitive impairment, functional decline, and death. Postoperative delirium is also associated with an increased length of hospital stay and higher costs. With the goal of preventing delirium in postoperative patients, we organized a medical team from the Delirium Management and Assessment Center (D-mac) at Okayama University Hospital in January 2012. The team members consisted of physicians, pharmacists, nurses, and clinical psychologists. METHODS: We retrospectively reviewed the medical records of patients with delirium to examine risk factors related to the patients' background. RESULTS: Fifty-nine postoperative patients with lung or esophageal cancer were investigated; 25% exhibited delirium during hospitalization. Multiple logistic regression analysis showed significant associations between the presence of delirium and a past history of delirium (odds ratio, 4.22; 95% CI, 1.10-16.2; p = 0.09) and use of benzodiazepine receptor agonists (odds ratio, 3.97; 95% CI, 1.09-14.5; p = 0.03). Intervention by the D-mac significantly reduced the rate of delirium episodes in lung cancer patients (p =0.01). Notably, prior to intervention, the incidence of delirium was 100% when three high-risk factors for delirium were present. In contrast, the incidence of delirium in patients with three high-risk factors decreased following implementation of the D-mac intervention. CONCLUSIONS: These findings suggest that active participation by various staff in the medical team managing delirium had a marked therapeutic impact. PMID- 26819716 TI - Photostability studies on (+/-)-tramadol in a liquid formulation. AB - BACKGROUND: Tramadol ((+/-)-TRA) is recommended for the treatment of mild to moderate cancer pain by the World Health Organization. An oral liquid formulation of (+/-)-TRA is preferable for patients with a compromised swallowing function. However, the stability of (+/-)-TRA in aqueous solution has yet to be determined in a clinical setting. The aim of this study was to evaluate the photostability of (+/-)-TRA in aqueous solution in a clinical setting. METHODS: We improved high performance liquid chromatography (HPLC) method for the enantiomeric separation of (+/-)-TRA, and then the (+/-)-TRA concentration was determined using HPLC method. We investigated the photodegradation of (+/-)-TRA in an aqueous solution irradiated with ultraviolet (UV) light: UV-A, UV-B, and UV-C. We also evaluated the stability of liquid formulations of (+/-)-TRA in a clinical setting by keeping (+/-)-TRA aqueous solution in normal dispensing bottles and in light shading dispensing bottles under conditions of both sunlight and diffused light in a room. Samples were collected sequentially over time. RESULTS: (+/-)-TRA in aqueous solution was degraded the most rapidly when irradiated with UV-C, but was not affected by irradiation with UV-A. No significant difference was observed in the photodegradation behavior of (+)-TRA and (-)-TRA with UV-A, UV-B, and UV-C irradiation. The residual percentages of (+/-)-TRA were 94.6-104.3% after 14 days in the presence of either sunlight or diffused light in a room, with or without protection from light. CONCLUSIONS: These results demonstrated the stability of (+/-)-TRA in aqueous solution to both sunlight and diffused light in a room. Therefore, liquid formulations of TRA are preserved at room temperature for up to 2 weeks, with or without protection from light. Our results provide additional treatment options with tramadol for pain control. PMID- 26819717 TI - Effectiveness of medical supportive team for outpatients treated with sorafenib: a retrospective study. AB - BACKGROUND: It is well known that molecular-targeted drugs, of which sorafenib (Nexavar(r)) is one, differ from previous anticancer drugs and cause various unusual adverse drug reactions. Treatment with sorafenib causes adverse drug reactions such as hand-foot skin reactions, hypertension, and diarrhea. Physicians spend a lot of time monitoring adverse drug reactions to sorafenib in outpatients. As such, at Okayama University Hospital, pharmacists and nurses have organized a medical supportive team to help physicians in this regard. However, the effectiveness of interventions for sorafenib-treated outpatients by this medical supportive team remains unclear. The purpose of this study was thus to clarify the effectiveness of interventions for sorafenib-treated outpatients by this medical supportive team. METHODS: We retrospectively studied 70 outpatients treated with sorafenib between May 2009 and December 2012 at Okayama University Hospital. These outpatients were classified into two groups, an intervention group (31 outpatients) and a non-intervention group (39 outpatients). We compared the duration of sorafenib treatment between these groups. RESULTS: The duration of treatment with sorafenib was significantly longer in the intervention group than in the non-intervention group. No outpatients in the intervention group discontinued sorafenib due to adverse drug reactions such as hand-foot skin reactions or diarrhea. CONCLUSION: The duration of sorafenib treatment was significantly longer in the intervention group than in the non-intervention group. Our findings suggest that interventions by the medical supportive team consisting of health care professionals were effective in preventing the discontinuation of sorafenib. PMID- 26819719 TI - Correlation of plasma crizotinib trough concentration with adverse events in patients with anaplastic lymphoma kinase positive non-small-cell lung cancer. AB - BACKGROUND: Crizotinib, an ATP-competitive receptor tyrosine kinase inhibitor of both anaplastic lymphoma kinase (ALK) and the hepatocyte growth factor receptor, commonly causes several adverse events (AEs). The clinical utility of measuring the plasma concentration of crizotinib in patients with non-small-cell lung cancer (NSCLC) has not been fully elucidated. The aim of this study was to evaluate the variability in the crizotinib trough concentration and its relationship with the occurrence of AEs in NSCLC patients. FINDINGS: Plasma samples were collected from 9 ALK fusion gene-positive NSCLC Japanese patients at day 14 after the first administration of crizotinib. We assessed crizotinib induced AEs on days 7, 14, 21, and 28. The crizotinib trough concentration on day 14 ranged from 243.5 to 847.8 ng/mL, and all of the patients achieved stable disease based on assessment of the tumor response on day 28. The cumulative number of AEs on day 28 in the higher trough concentration group was approximately 3-fold greater than that in the lower trough concentration group. AEs of grade 3 or 4 were observed only in patients in the higher trough concentration group. CONCLUSIONS: The occurrence of several AEs may correlate with the increase in the crizotinib trough concentration. Monitoring of the crizotinib trough concentration could predict the risk of development of several AEs and provide guidance for determining the optimal dose of crizotinib. PMID- 26819718 TI - Prescription rate of medications potentially contributing to lower urinary tract symptoms and detection of adverse reactions by prescription sequence symmetry analysis. AB - BACKGROUND: The lower urinary tract symptoms (LUTS) increases with age and can have a significant effect on the quality of life of the patients. Elderly patients, who are often characterized by a decline in physiological functional and polypharmacy, are susceptible to adverse drug reactions to pharmacotherapy. LUTS can also be a side effect of medication. The purpose of this study was to investigate the possible association between the initiation of LUTS-causing drug therapy and the onset of LUTS. METHODS: Drug dispensing data at the individual level were retrieved from the CISA (Platform for Clinical Information Statistical Analysis: http://www.cisa.jp) database. A retrospective study was conducted by reviewing patients with LUTS who were dispensed drugs that increased the risk of LUTS between April 2011 and March 2012. Prescription sequence symmetry analysis (PSSA) was employed to investigate the associations between the dispensing of medicines of LUTS and that of LUTS-causing drugs. RESULTS: LUTS-causing drugs were frequently dispensed to patients with LUTS. The use of medications potentially contributing to LUTS was associated with polypharmacy [number of prescription drugs:12.13 +/- 6.78 (user) vs. 5.67 +/- 5.24 (nonuser)] but not patient age [ age: (71.38 +/- 13.28 (user) vs. 70.45 +/- 14.80 (nonuser)]. Significant adverse drug events were observed the use of donepezil, cyclophosphamide, antiparkinson drugs, antidepressant, diazepam, antipsychotic drugs for peptic ulcer, tiotropium bromide, and opioids. CONCLUSIONS: The use of prescription LUTS-causing drugs was correlated with polypharmacy. The adverse drug events associated with LUTS-causing drugs were highly prevalent in elderly patients. To prevent of adverse drug events in patients with LUTS, pharmacists and physicians should regularly review medication lists and reduce the prescribed medicines. PMID- 26819720 TI - Supersaturated state of diazepam injection following dilution with infusion fluid. AB - BACKGROUND: Significant precipitation produced by the dilution of diazepam (DZP) injection with an infusion fluid is a great concern for the clinical practice. In this study, the precipitation behavior under different conditions was investigated. METHOD: For the sample preparation, DZP injections (Horizon injection and Cercine injection) were diluted with various infusion fluids (Saline, 5% glucose infusion fluid and Soldem 3A) at designated dilution ratios ranging from 1* to 40* (5 mg/mL to 0.125 mg/mL). In addition, to measure the solubility of DZP in the samples, the saturated solutions of DZP were prepared. The DZP concentrations in the samples were measured by high-performance liquid chromatography (HPLC). This study also investigated the precipitate using various analytical methods: infrared microscopy, (1)H-NMR, differential scanning calorimetry, and powder X-ray deflection. RESULTS: First, the compatibility of injection with infusion fluids was investigated. Significant precipitation occurred at dilution ratios ranging from 2* to 20*. No significant effects of formulations and infusion fluids on the compatibility were observed. The solubility of DZP was then further investigated. The concentration of DZP dissolved in the admixtures was higher than the solubility. This indicated that DZP existed in a supersaturated state in the infusion fluid admixtures. In the next phase of this study, the precipitate was investigated using various analytical methods. Results showed that the precipitate in infusion fluid admixtures was mostly composed of DZP, but also contained small amounts of the ingredients of DZP injection, such as benzoic acid and benzyl alcohol. CONCLUSIONS: This study clarified details of the precipitation occurring after dilution of DZP injection with infusion fluids. It is worth noting that DZP in an infusion admixture existed in a supersaturated state. These findings offer important insight into the clinical practice of DZP injection. PMID- 26819721 TI - Pharmacoeconomic effect of compliance with pharmacist's intervention based on cancer chemotherapy regimens: a cohort study. AB - BACKGROUND: It is important for pharmacists to manage cancer chemotherapy regimens in order to achieve safe treatment. We examined whether there was a useful pharmacoeconomic benefit of compliance the exclusion criteria of neutropenia, and the importance of a pharmacist's intervention was considered. METHODS: A prospective observational cohort study was conducted at a community based medical center. Among 374 patients who received chemotherapy between April 2010 and March 2011, 108 patients developed neutropenia and pharmacists recommended suspension of chemotherapy. These patients were divided into a group in whom chemotherapy was suspended (complying group) and a group in whom it was continued (non-complying group). Then the relative dose intensity (RDI) was compared between the two groups, and medical expenses related to the treatment of neutropenia (neutropenia-related costs: NRC) were compared. Analysis was carried out from the perspective of the health insurance provider, so only the direct medical costs were evaluated. RESULTS: There was a significant difference of the RDI between a complying group (85.2 +/- 10.0%) and a non-complying group (79.3 +/ 15.0%) (P = 0.021). The average NRC per patient showed a significant difference between the two groups (complying group: 1,944 +/- 412 dollars, non-complying group: 4,394 +/- 837 dollars, P = 0.044). The economic effect over one year was 54,205 dollars. CONCLUSION: The present findings suggest that ensuring compliance with chemotherapy regimens (including the criteria for neutropenia) is effective from a pharmacoeconomic perspective. Accordingly, pharmacists should intervene as required to improve regimen compliance. PMID- 26819722 TI - Relationship between incident types and impact on patients in drug name errors: a correlational study. AB - BACKGROUND: There are many reports regarding various medical institutions' attempts at incident prevention, but the relationship between incident types and impact on patients in drug name errors has not been studied. Therefore, we analyzed the relationship between them, while also assessing the relationship between preparation and inspection errors. Furthermore, the present study aimed to clarify the incident types that lead to severe patient damage. METHODS: The investigation object in this study was restricted to "drug name errors", preparation and inspection errors in them were classified into three categories (similarity of drug efficacy, similarity of drug name, similarity of drug appearance) or two groups (drug efficacy similarity (+) group, drug efficacy similarity (-) group). Then, the relationship between preparation and inspection errors was investigated in three categories, the relationship between incident types and impact on patients was examined in two groups. RESULTS: The frequency of preparation errors was liable to be caused by the following order: similarity of drug efficacy > similarity of drug name > similarity of drug appearance. In contrast, the rate of inspection errors was liable to be caused by the following order: similarity of drug efficacy < similarity of drug name < similarity of drug appearance. In addition, the number of preparation errors in the drug efficacy similarity (-) group was fewer than that in the drug efficacy similarity (+) group. However, the rate of inspection errors in the drug efficacy similarity (-) group was significantly higher than that in the drug efficacy similarity (+) group. Furthermore, the occupancy rate of preparation errors, incidents more than Level 0, 1, and 2 in the drug efficacy similarity (-) group increased gradually according to the rise of patient damage. CONCLUSIONS: Our results suggest that preparation errors caused by the similarity of drug appearance and/or drug name are likely to lead to the incidents (inspection errors), and these incidents are likely to cause severe damage to patients subsequently. PMID- 26819723 TI - Adherence to changing from brand-name to generic atorvastatin in newly treated patients: a retrospective cohort study using health insurance claims. AB - BACKGROUND: Effect of statin therapy has been reported to be associated with patient's adherence. Atorvastatin was available in Japan as a brand-name product beginning in 2000. The first atorvastatin generics were introduced in Japan in November 2011. The objective of this study was to analyze whether changing from a brand-name atorvastatin to a generic product would affect patient adherence. METHODS: We conducted a retrospective cohort study that included adult patients who received newly prescribed brand-name atorvastatin between June 1, 2011 and May 31, 2012, using a health insurance claims database in Japan. Patients were classified by the presence or absence of changing to a generic during the 6 months from December 1, 2011 to May 31, 2012 (the index period). The first prescription date for the generic or brand product during the index period was defined as the index date. Adherence to therapy was assessed by the proportion of days covered (PDC) and persistence of treatment by time to discontinuation. RESULTS: There were 135 patients changing to generic atorvastatin and 147 continuing with the brand-name product. There was no significant difference in decrease of PDC from pre- to post-index date between the changed cohort and continued cohort (-8.6% vs -10.3%, respectively; P = 0.443). After adjusting for baseline covariates, including adherence in pre-index date, no statistically significant differences were observed in the adjusted odds of adherence between the cohorts (adjusted odds ratio = 0.83, 95% confidence interval (CI) = 0.46 1.53). There was also no significant difference in persistence between two cohorts in the 180-day after post-index date. After analysis of a Cox proportional hazard regression model controlling for baseline covariates, including adherence in pre-index date, no statistically significant differences were observed for the hazard of non-persistence between the cohorts (adjusted hazard ratio = 0.96, 95% CI = 0.60-1.53). CONCLUSIONS: Changing from a brand-name atorvastatin to generic product did not affect adherence for patients newly treated with atorvastatin. PMID- 26819724 TI - Onset of analgesia with ibuprofen sodium in tension-type headache: a randomized trial. AB - BACKGROUND: Ibuprofen is known to be efficacious in the treatment of tension-type headache, the most common form of primary headache. A novel tablet formulation of ibuprofen sodium is more rapidly absorbed than standard ibuprofen. This study evaluated onset of analgesia and overall efficacy of ibuprofen sodium in episodic type tension headache (ETTH) compared with standard ibuprofen and placebo. METHODS: This randomized, double-blind, single-center, parallel-group study included adults aged 18-65 years with >=4 moderately severe ETTHs per month for 6 months. Within 45 minutes of onset of at least moderately severe ETTH, subjects were randomized 2:2:1 to receive a single oral dose of ibuprofen sodium tablets (Advil(r) Film Coated; 2 * 256 mg [equivalent to 400 mg standard ibuprofen]), standard ibuprofen tablets (Motrin(r); 2 * 200 mg), or placebo. The coprimary end points were time-weighted sum of pain relief rating and pain intensity difference scores over 3 hours (SPRID 0-3) and time to meaningful pain relief (MPR) assessed by double-stopwatch method. RESULTS: A total of 226 subjects were randomized to ibuprofen sodium (n = 91), standard ibuprofen (n = 89), and placebo (n = 46). Demographics and baseline characteristics were comparable between treatment groups. Mean SPRID 0-3 scores were significantly superior (P < .001) for ibuprofen sodium (9.6) and standard ibuprofen (9.8) versus placebo (3.5), but were not significantly different from each other (P = .812). Time to MPR was significantly (P < .001) shorter for ibuprofen sodium and standard ibuprofen compared with placebo (median 40.6, 48.5, and >180 minutes, respectively). Time to MPR was numerically faster for ibuprofen sodium than standard ibuprofen. This difference was not statistically significant (P = .253) using the protocol specified analysis but was (P = .022) in a post hoc analysis using the Gehan Wilcoxon test, which assigns higher weights to earlier events. (The post hoc analysis was performed because Kaplan-Meier graphs and results for time to first perceptible relief favored ibuprofen sodium over standard ibuprofen at earlier time points.) There were no adverse events. CONCLUSIONS: This novel ibuprofen sodium tablet provided rapid, efficacious relief of ETTH and was well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov NCT01362491. PMID- 26819725 TI - Meta-analysis of the efficacy and safety of Ginkgo biloba extract for the treatment of dementia. AB - BACKGROUND: The benefit of Ginkgo biloba for the treatment of dementia remains controversial. The aim of this study was to evaluate the efficacy and safety of Ginkgo biloba in patients with dementia in whom administration effects were reported using meta-analysis. METHODS: We searched MEDLINE, Embase, the Cochrane databases, and Ichushi for controlled trials of Ginkgo biloba for the treatment dementia. Clinical characteristics and outcomes were extracted. Meta-analysis results were expressed as standard mean differences (SMDs) in scores of the Syndrome Kurztest (SKT), Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) for cognition efficacy, or odds ratios (ORs) for dropouts and adverse drug reactions. RESULTS: Thirteen studies using the extract EGb761 met our inclusion criteria, which were duration of 12 to 52 weeks and daily dose of more than 120 mg, and included a total of 2381 patients. Meta-analysis was performed by using 9 of 13 studies, 7 of which used the SKT and 2 ADAS-Cog (dose 120 mg, 26 weeks) scores as efficacy parameters. In meta-analysis of all patients, SMDs (95% confidence interval [CI]) in the change in SKT scores (7 studies) were in favor of Ginkgo biloba over placebo (SMD = -0.90 [-1.46, -0.34]), but 2 studies that used ADAS-Cog did not show a statistically significant difference from placebo for ADAS-Cog (-0.06 [-0.41, 0.30]). For Alzheimer's disease (AD) and vascular dementia (VaD) subgroups, SMDs [95% CI] in SKT in the combined AD and VaD subgroup (-1.07 [-1.66, -0.47]) and AD subgroup (-1.36 [-2.27, -0.46]) were in favor of Ginkgo biloba over placebo. In terms of daily dose of Ginkgo biloba in the combined AD and VaD subgroup, SMD in SKT score in 240-mg daily dose groups was significantly greater than with placebo (-0.71 [-1.28, -0.14]). Dropout rates for any reason did not differ between two groups, but dropout rates due to side effects were significantly lower in Ginkgo biloba groups compared with placebo groups (OR = 1.72 [1.06, 2.80]). CONCLUSIONS: Taking a 240-mg daily dose of Ginkgo biloba extract is effective and safe in the treatment of dementia. PMID- 26819726 TI - Hyperglycemic adverse events following antipsychotic drug administration in spontaneous adverse event reports. AB - BACKGROUND: Antipsychotics are potent dopamine antagonists used to treat schizophrenia and bipolar disorder. The aim of this study was to evaluate the relationship between antipsychotic drugs and adverse hyperglycemic events using the FDA Adverse Event Reporting System (FAERS) database. In particular, we focused on adverse hyperglycemic events associated with atypical antipsychotic use, which are major concerns. FINDINGS: We analyzed reports of adverse hyperglycemic events associated with 26 antipsychotic drugs in the FAERS database from January 2004 to March 2013. The Standardized Medical Dictionary for Regulatory Activities Queries (SMQ) preferred terms (PTs) was used to identify adverse hyperglycemic events. The number of adverse hyperglycemic reports for the top eight antipsychotic drugs, quetiapine, olanzapine, risperidone, aripiprazole, haloperidol, clozapine, prochlorperazine, and chlorpromazine was 12,471 (28.9%), 8,423 (37.9%), 5,968 (27.0%), 4,045 (23.7%), 3,445 (31.5%), 2,614 (14.3%), 1,800 (19.8%), and 1,003 (35.7%), respectively. The reporting ratio increased with co administration of multiple antipsychotic drugs. For example, adverse hyperglycemic events represented 21.6% of reports for quetiapine monotherapy, 39.9% for two-drug polypharmacy, and 66.3% for three-drug polypharmacy. CONCLUSION: Antipsychotic drug polypharmacy may influence signal strength, and may be associated with hyperglycemia. After considering the causality restraints of the current analysis, further robust epidemiological studies are recommended. PMID- 26819727 TI - Pharmacoepidemiology in Japan: medical databases and research achievements. AB - Pharmacoepidemiology involves development of new models to predict safety in the development stages of pharmaceutical products, development of various guidelines and policy related to clinical trials, pharmacovigilance, establishment and implementation of risk management in postmarketing studies, and cost effectiveness research in medical and social welfare sectors. Evaluations of safety, efficacy, and costs of pharmaceutical products must be developed in a different way. More recently, "big data" in medicine have become the driving force behind epidemiological studies that attempt to solve questions in the clinical setting. Furthermore, it is important to pursue cost-effectiveness considering the government's financial condition. Epidemiologic and economic research utilizing epidemiological data linked to cost data will provide scientific evidence for appropriate distribution of health resources. PMID- 26819728 TI - The influence of dietary peptide inhibitors of angiotensin-converting enzyme on the hypotensive effects of enalapril. AB - BACKGROUND: Enalapril is an antihypertensive medicine that inhibits angiotensin I converting enzyme (ACE). The present study investigated interactions between enalapril and a fermented milk product (FMP) containing the ACE-inhibitory peptides, Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP). METHODS: Single-dose and long term (6-week) in vivo studies were used to investigate the effects of enalapril and FMP on blood pressure in spontaneously hypertensive rats. RESULTS: Single dose oral administration of concomitant enalapril and FMP (VPP, IPP: 3.5 mg/kg) produced a lower antihypertensive effect than enalapril monotherapy. However, this effect was not observed in animals administered a lower dose of FMP (VPP, IPP: 1.75 mg/kg) along with enalapril. In rats administered enalapril concomitantly with a fish protein product (FPP) containing a different ACE inhibitory peptide (Leu-Lys-Pro-Asn-Met), significant attenuation of the antihypertensive effect was also observed 1 and 2 h after administration, as compared to enalapril monotherapy. During a 6-week oral administration study, the enalapril monotherapy group showed significant antihypertensive effects compared to those observed in the controls on day 28. Oral administration of enalapril and FMP, with a 1-h interval between doses, resulted in significant antihypertensive effects on day 35, indicating a delayed onset in comparison to enalapril monotherapy. In rats receiving enalapril monotherapy for 28 days, followed by 14 days of concomitant FMP, significant antihypertensive effects were observed after day 35, and these did not differ significantly from the effects observed during enalapril monotherapy. CONCLUSIONS: The present findings suggested that long-term concomitant intake of FMP and enalapril could influence the antihypertensive effects of this drug. PMID- 26819729 TI - Evaluation of pharmacy practice program in the 6-year pharmaceutical education curriculum in Japan: hospital pharmacy practice program. AB - BACKGROUND: The objective of this study was to clarify the state of national pharmacy practice program in the 6-year course of pharmaceutical education from the students' point of view. We will suggest the points for improvement and issues of the current pharmacy practice programs to enhance the educational effects of the pharmacy practice program. METHODS: The survey conducted from September 2011 to March 2012 (hereinafter referred to as "2011") and from September 2012 to March 2013 (hereinafter referred to as "2012") comprised 1,607 pharmacy students, who had completed the pharmacy practice program. They were asked to fill out a self-descriptive questionnaire for the purpose of investigating the content of the pharmacy practice that the students themselves experienced, guidance provided by the supervising pharmacists, and support by the university faculty staff. RESULTS: In order to clarify the factor structure of the overall results, four factors were extracted through an exploratory analysis: "satisfactory learning", "support system of the training site (hospital)", "support system of university", and "dialogue with patients". When we compared the score for each four factors between 2011 and 2012 and we found that 2012 was evaluated as significantly higher for all factors. Furthermore, opportunities for discussion and reflection with the students led to observation that 2012 exhibited significantly better results than 2011. CONCLUSIONS: The students evaluations for the quality of hospital pharmacy practice have improved in 2012 compared to evaluations in 2011. Regarding the four factors of "satisfactory learning", "support system of the training site", "support system of university", and "dialogue with patients", significant differences in the results from 2011 and 2012 were observed, indicating their marked improvement. PMID- 26819730 TI - Differences in recognition of similar medication names between pharmacists and nurses: a retrospective study. AB - BACKGROUND: Differences in error rates between pharmacists and nurses in terms of drug confirmation have not been studied. The purpose of this study was to analyze differences in error rates between pharmacists and nurses from the viewpoint of error categories, and to clarify differences in recognition regarding drug name similarity. METHODS: In this study, preparation errors and incidents were classified into three categories (drug strength errors, drug name errors, and drug count errors) to investigate the influence of error categories on pharmacists and nurses. In addition, errors in two categories (drug strength errors and drug name errors) were reclassified into another two error groups, to investigate the influence of drug name similarity on pharmacists and nurses: a "drug name similarity (-) group" and a "drug name similarity (+) group". Then, differences in error rates of pharmacists and those of nurses were analyzed respectively within three categories and two groups. Furthermore, differences in error rates between pharmacists and nurses were analyzed in each of the three categories and two groups. RESULTS: Error rates of pharmacists for both drug strength errors and drug name errors were significantly higher than that for drug count errors, and similar results were obtained for nurses (P < 0.05). However, there were no significant differences in error rates between pharmacists and nurses in each of the three categories. Furthermore, error rate of nurses was significantly higher than that of pharmacists in the drug name similarity (+) group (P < 0.05), while there was no significant difference in error rates between pharmacists and nurses in the drug name similarity (-) group. CONCLUSIONS: These results suggest that in contrast to pharmacists, nurses are easily affected by similarities in drug names. Therefore, pharmacists should offer information on medications having plural strengths or similar names to nurses, in order to minimize damage to patients resulting from errors. PMID- 26819731 TI - Prevention of the exposure by cyclophosphamide oral tablet. AB - BACKGROUND: Unintended exposure to antitumor agents from an oral medicine may place healthcare workers and patients taking medicine at risk. In this study, the exposure to blister pack by CP (cyclophosphamide) and appropriate preventive procedures were examined. FINDINGS: CP detected inside the blister pack of the tested seven lots by LC-MS/MS ranged from 8.2 to 199.6 ng. Raman imaging clearly showed that CP ingredient was completely covered by the tablet coating layer and had not leached out of the tablet. In addition, the amount of CP detected inside the vials was suppressed under the lower detection limit until day 28, and only 6.0 ng was detected only at day 56. CONCLUSIONS: Various amounts of CP were contaminated to not only the inside of the blister pack but also the outside. This contamination may be caused not only by the manufacturing environment but also by the CP oral tablets themselves through volatilization of CP. Refrigerated storage of CP oral tablets may protect healthcare workers and patients from contact with CP. PMID- 26819732 TI - Active topical therapy by "Furuta method" for effective pressure ulcer treatment: a retrospective study. AB - BACKGROUND: We newly proposed that "Furuta method," a pharmacist intervention guidelines, is a topical ointment therapy that considers the physical properties and moist environment of wounds for pressure ulcer (PU) treatment. The aim of this multicenter retrospective study was to investigate the effectiveness of this method for PU. METHODS: A total of 888 consecutive patients who underwent treatment for PU at 37 hospitals and five dispensing pharmacies in Japan between August 2010 and July 2014 were included in the study. Based on a survey on compliance to "Furuta method," single-blind allocation was conducted into compliance (n = 437) and non-compliance (n = 451) groups, followed by a retrospective data collection. The primary and secondary outcomes were the healing period and rates of unhealed wounds, respectively. Data was expressed as mean +/- standard deviation. Two-sided log rank tests were used for between-group comparisons of PU progression, whereas Kaplan-Meier plots were used for comparison between groups. We performed rigorous adjustment for marked differences in baseline patient characteristics by propensity score (PS) matching. RESULTS: After PS matching, patients were categorized as DESIGN-R d2 (n = 202), D3 (n = 130), D4 and 5 (n = 76), and DU (n = 76). In terms of the healing period, the patients in the compliance groups healed faster than those in the non compliance groups in d2 (23.6 +/- 36.8 vs. 32.2 +/- 16.6 days; P < 0.001), D3 (46.8 +/- 245.5 vs.137.3 +/- 52.7 days; P < 0.001), and D4, 5 (122.5 +/- 225.7 vs. 258.2 +/- 292.7 days; P < 0.001). There were significantly lesser events of PU progression in the compliance group than in the non-compliance group (15 vs. 54; P = 0.003). CONCLUSIONS: "Furuta method" is the new therapeutic strategy of PU, a pharmacist intervention guidelines, may possibly increase healing rates of PUs. PMID- 26819733 TI - A retrospective study to identify risk factors for somnolence and dizziness in patients treated with pregabalin. AB - BACKGROUND: Pregabalin is a therapeutic drug for neuropathic pain that is associated with somnolence and dizziness. These adverse events are often experienced shortly after initiating pregabalin, and may lead to treatment discontinuation. The purpose of this study was to explore factors that influence the incidence of somnolence and dizziness induced by pregabalin, and to identify patients at higher risk of adverse events. METHODS: A retrospective analysis was conducted of patient characteristics (age, gender, renal function, initial daily dose of pregabalin, co-administration of strong opioids and hypnotics) and the incidence of somnolence and dizziness during the first week of pregabalin treatment. An electronic chart was used to collect data from 204 inpatients prescribed pregabalin at Nagoya University Hospital from June 2011 to November 2012. RESULTS: Among 36 patients who regularly received strong opioids, 18 (50.0 %) reported somnolence or dizziness during the first week of pregabalin treatment. The remaining 168 patients did not regularly receive strong opioids, and 25 (14.9 %) had an adverse event. In multivariate analysis, age (?65 years, adjusted odds ratio: 2.507, 95 % CI: 1.164-5.397, p = 0.019) and regular co administration of strong opioids (adjusted odds ratio: 5.507, 95 % CI: 2.460 12.328, p < 0.001) correlated with somnolence or dizziness. CONCLUSIONS: These data suggest that age (?65 years) and co-administration of strong opioids are risk factors for somnolence or dizziness during pregabalin treatment for neuropathic pain. More careful dose titration is recommended for elderly patients and those receiving concomitant strong opioids. PMID- 26819734 TI - Effects of an evidence-based medicine workshop on Japanese pharmacy students' awareness regarding the importance of reading current clinical literature. AB - BACKGROUND: Drug literature evaluation has been taught at pharmacy schools in the United States, allowing pharmacy students to learn how to read clinical literature critically. In advanced pharmacy practice experiences, preceptors often assign pharmacy students to journal clubs in which they repeatedly train how to read such literature. This enables them to understand the importance of reading clinical literature prior to graduation. The objective of this study was to create evidence-based medicine (EBM) workshop that would enhance Japanese pharmacy students' awareness regarding the importance of reading up-to-date clinical literature. METHODS: The EBM workshop were designed as a one-day workshop consisting of student presentations regarding their opinions about reading clinical literature, a lecture on methods for reading required literature critically, and small group discussions using the KJ (Kawakita Jiro) Method. To evaluate the effectiveness of the EBM workshop, students were administered questionnaire surveys both before and after the workshop. The students also took a 15-question test on EBM. Regarding the questionnaires, students were asked to respond to dichotomous items (yes/no) and to indicate on a 7-point Likert scale the extent to which they agreed with statements about clinical literature. Student responses to both the pre- and post-workshop questionnaires were then compared to evaluate the effectiveness of the EBM workshop. RESULTS: A total of 37 students participated in the EBM workshop. Significant improvement was seen between the pre- and post-workshop questionnaires in responses regarding whether they thought that pharmacists should read clinical literature regularly (pre workshop: 5.70 +/- 0.17 versus 6.51 +/- 0.13 post-workshop; p < 0.0001), whether they were confident in their ability to read clinical literature (1.81 +/- 0.15 versus 3.92 +/- 0.18; p < 0.0001), and whether they could discuss treatment with nurses and physicians based on the results of clinical literature if they were a hospital pharmacist (2.49 +/- 0.22 versus 3.86 +/- 0.21; p < 0.0001). Significant improvement was also seen in scores on the EBM tests (11.4 +/- 0.29 versus 12.6 +/- 0.22; p < 0.0001). CONCLUSION: Our EBM workshop significantly enhanced student awareness regarding the importance of reading up-to-date clinical literature. It is therefore expected that students who participated in our EBM workshop will contribute to improvements in the quality of the pharmacy profession in the future. PMID- 26819735 TI - Retrospective investigation of combination therapy with clarithromycin and levofloxacin for pulmonary Mycobacterium avium complex disease. AB - BACKGROUND: Fluoroquinolones are often used for the treatment of refractory Mycobacterium avium complex (MAC) disease when the clinical efficacy of the recommended regimen, which includes clarithromycin (CAM), rifampicin (RFP), and ethambutol (EB), is insufficient. However, recent in vitro and in vivo studies have suggested that fluoroquinolones decreased the antibacterial activity of CAM when they were administered in combination. In this study, we retrospectively investigated the influence of the combination of CAM and levofloxacin (LVFX) on clinical outcomes for pulmonary MAC disease patients. METHODS: Pulmonary MAC disease patients from 2010 to 2012 were divided into two groups, those who received LVFX together with CAM (LVFX group) and those who received CAM without LVFX (control group). The number of patients who showed improvement was evaluated at 1, 3, 6 and 12 months after the start of therapy based on bacteriological examination (culture and smear examination) and the bacilli negative conversion rate. RESULTS: There were no significant differences between the LVFX group (n = 18, 64.5 +/- 6.5 years old) and the control group (n = 57, 71.0 +/- 7.0 years old) in terms of gender, age, etiologic agent, baseline culture examination score, concomitant medication, and dosage of each drug. The clinical outcomes in the LVFX group were inferior to those in the control group at all endpoints and observational periods, and we found a significant difference in the percent improvement of the smear examination by fluorescence microscopy method (38 % vs. 83 %) and the bacilli negative conversion rate (38 % vs. 79 %) at 3 months. Our study suggests that the combination of CAM and LVFX causes unfavorable clinical outcomes for pulmonary MAC disease treatment. There was no significant difference between both groups in terms of frequency of adverse events. CONCLUSION: The possibility that combined administration of CAM and LVFX causes unfavorable clinical outcomes for pulmonary MAC disease treatment was suggested. PMID- 26819736 TI - Population pharmacokinetics and optimization of the dosing regimen of digoxin in adult patients. AB - BACKGROUND: This study aimed to evaluate the population pharmacokinetics of digoxin in Japanese patients and establish a dosage regimen based on the pharmacokinetic data. METHODS: We analyzed 287 serum digoxin samples from 192 individuals by using the nonlinear mixed effects model. We used simulations to optimize the dosage regimen of digoxin to achieve a high likelihood of the target concentration (0.5-0.8 ng/mL). RESULTS: The total body clearance (CL/F ([L/h]) was calculated using the following formula: CL/F = (1.21 + 0.0532 * CLcr [(mL/min]) * (1 + 0.787 * AMD), where CLcr is the creatinine clearance and AMD is 0 in the case of concomitant administration of amiodarone and 1 otherwise. To achieve the target concentration (0.5-0.8 ng/mL), the dosage of digoxin was 0.0625 mg/day (CLcr < 35 mL/min and AMD = 0); 0.125 mg/day (CLcr, 35-65 mL/min and AMD = 0); 0.1875 mg/day (CLcr, 65-100 mL/min and AMD = 0); 0.0625 mg/every other day (CLcr < 30 mL/min and AMD = 1); and 0.0625 mg/day (CLcr, 30-85 mL/min and AMD = 1). CONCLUSIONS: Our findings suggest that population parameters are useful for evaluating digoxin pharmacokinetics. PMID- 26819737 TI - Effect of switching basal insulin regimen to degludec on quality of life in Japanese patients with type 1 and type 2 diabetes mellitus. AB - BACKGROUND: Maintainance of a stable basal insulin level is important for glycemic control in treatment of diabetes mellitus. Recently introduced insulin degludec has the longest duration of action among basal insulin formulations. The purpose of this study was to assess changes in quality of life (QOL) associated with switching the basal insulin regimen to degludec in patients with type 1 and type 2 diabetes mellitus. METHODS: This 24-week open-label intervention study included type 1 (n = 10) and type 2 (n = 20) diabetes mellitus patients, with adequately controlled hemoglobin A1c (HbA1c), who had received insulin glargine or detemir for at least 6 months. The primary outcome was change of QOL from baseline, as assessed by the Diabetes Therapy-Related QOL (DTR-QOL) application, after switching from glargine or detemir to degludec. HbA1c and other parameters were also assessed as secondary outcomes. RESULTS: QOL and HbA1c in patients with type 1 diabetes mellitus were unchanged during this study. In patients with type 2 diabetes mellitus, HbA1c did not change, but total DTR-QOL score was significantly improved from baseline after switching to degludec. The DTR-QOL Factor 2, "Anxiety and dissatisfaction with treatment", was significantly improved in patients with type 2 diabetes mellitus and especially in the subgroup receiving basal supported oral therapy (BOT). CONCLUSIONS: Switching of the basal insulin regimen from glargine or detemir to degludec significantly improved the QOL of patients with type 2 diabetes mellitus who were receiving BOT, by reducing mental stress or anxiety about their treatment. PMID- 26819738 TI - Evaluation of the pharmacy practice program in the 6-year pharmaceutical education curriculum in Japan: community pharmacy practice program. AB - BACKGROUND: The purpose of this study was to highlight concerns with the current pharmacy practice program and suggest aspects for improvement. A further aim of the study was to enhance the educational effects of the program, from the students' point of view. METHODS: We surveyed 1,607 pharmacy students in Japan who had completed the pharmacy practice program in either 2010 or 2011. The students completed a self-descriptive questionnaire comprising 48 questions examining their experience of the pharmacy practice program. RESULTS: For community pharmacy practice, four factors were extracted through exploratory analysis: "satisfactory learning (pharmacy)," "support system of the university," "creation and clarification of the training plan," and "dialogue with patients." When comparing the mean values for each of the four factors between 2011 and 2012, the 2012 group scored significantly higher (p < 0.001) on "support system of the university" only. In the free responses, it became apparent that, for the joint training held in certain regions, students evaluated such training to be useful and effective. Moreover, we conducted an overall evaluation of the pharmacy practice programs. From the results of McNemar's test, from 2011 to 2012, there was a significant decrease in the number of students who were unable to experience "charge system of patients" at neither hospitals nor pharmacies (p < 0.01). CONCLUSIONS: For community pharmacy practice, there were no significant differences found for the factors, with the exception of the "support system of the university." In addition, to accomplish the learning objectives, community pharmacy practice program introduced some initiatives. Furthermore, conducting training at multiple facilities deepens student learning and assists with the correction of problems, such as the disparities within the teaching system and learning content at each of the training facilities. PMID- 26819739 TI - Switching from allopurinol to febuxostat: efficacy and tolerability in hemodialysis patients. AB - BACKGROUND: Febuxostat is a novel xanthine oxidase inhibitor. However, few studies have examined the long-term efficacy and tolerability of febuxostat after switching from allopurinol in hemodialysis (HD) patients. Therefore, the present study evaluated the long-term efficacy and tolerability of febuxostat in HD patients after switching from allopurinol. FINDINGS: We monitored the levels of hemoglobin, hematocrit, platelet count, blood urea nitrogen, serum creatinine, serum sodium, serum potassium, serum chloride, serum calcium, serum inorganic phosphorus, aspartate transaminase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, and total protein that were considered overall as a tolerability index, while the serum uric acid (UA) level was considered an index of efficacy. All values were measured at baseline and at 1, 6, 12, and 16 months after the switch to febuxostat therapy. All subjects switched from allopurinol (100 mg/day) to febuxostat (10 mg/day) in August 2013. Clinical laboratory data were collected at baseline in July 2013 until December 2014. Nine patients were included in the study analysis. Results showed that clinical laboratory data at baseline versus those at 16 months were not significantly different. Serum UA levels, which represented the efficacy index, were significantly different between the baseline level (6.8 +/- 1.4) and those at 1, 6, 12, and 16 months (5.2 +/- 1.1, 5.1 +/- 1.1, 4.6 +/- 0.9, and 5.4 +/- 1.8 mg/dL, respectively; all p < 0.05). CONCLUSION: Switching from allopurinol to febuxostat in HD patients reduced serum UA levels, with no changes in other clinical laboratory data in the long term. PMID- 26819740 TI - Outcomes of the implementation of the computer-assisted HBView system for the prevention of hepatitis B virus reactivation in chemotherapy patients: a retrospective analysis. AB - BACKGROUND: Screening for hepatitis B virus (HBV) infection is recommended worldwide for patients receiving systemic chemotherapy in accordance with clinical guidelines, but compliance varies by country and facility. Alert systems may be useful for promoting screening, but it is unclear how effective such systems are. In this study, we investigated HBV screening procedures and their incorporation into treatment regimens following the implementation of an alert system. METHODS: An alert system was introduced at our hospital in April 2012. The rates of HBV screening in the periods before and after the introduction of the alert system (September 2010 to March 2012 and April 2012 to October 2013, respectively) were investigated. We collected data on hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb), and HBV-DNA testing in patients. As a result of this analysis, we developed a system in which pharmacists would intervene to check and confirm whether HBV screening had occurred in patients scheduled to begin treatment with chemotherapy. We named our project the "HBView" project, and the rate of HBV screening and the number of times pharmacists intervened was studied during specific time periods before and after the HBView project commenced (July 2013 to December 2013 and January 2014 to June 2014, respectively). RESULTS: After introducing the alert system, the percentage of patients tested for HBsAb/HBcAb and HBV-DNA increased significantly, from 71.6 % to 84.9 % and from 44.5 % to 69.7 %, respectively. However, the rate of compliance with HBV testing guidelines was not 100 % after interventions. The numbers of patients who were not screened but should have been before and after the introduction of HBView were 6 and 17, respectively. Two patients at risk of HBV reactivation were identified after intervention by pharmacists; their intervention thus prevented HBV reactivation. CONCLUSIONS: Compliance with clinical HBV screening guidelines was not sufficiently improved after the introduction of the automatic alert system; however, the HBView project proved useful in reinforcing the automatic alert system. PMID- 26819741 TI - Opioid analgesics increase incidence of somnolence and dizziness as adverse effects of pregabalin: a retrospective study. AB - BACKGROUND: Pregabalin, a gabapentinoid, is an adjuvant analgesic for treatment of neuropathic pain, but it has serious adverse effects such as somnolence and dizziness, particularly in elderly patients. Although decreased renal function is considered to the contributing factor for high frequency of these adverse effects in elder patients, only a few systematic clinical investigations, especially for hospitalized patients, have been performed on factors that might affect the incidence of its adverse effects. In this study, we performed a retrospective study on the effect of concomitant drugs on induction of somnolence and dizziness as adverse effects of pregabalin in hospitalized patients. METHODS: The subjects were all pregabalin-administered patients in Shiga University of Medical Science Hospital from September 2010 to September 2012, and the subject number was 195. Multivariate logistic regression analysis was performed to determine predictors of the adverse effects, creatinine clearance, duration of pregabalin therapy, initial and maintenance doses of pregabalin, and concomitant drugs, including hypoglycemic drugs, anti-hypertensive ones, non-steroidal anti-inflammatory ones, opioids and central nervous system depressants, being used as independent variables. RESULTS: The median initial doses of pregabalin in each renal function group were the same with the case of the defined dose. Although renal function is a well-known factor for prediction of development of adverse effects of pregabalin, we did not detect significant contribution of it. Alternatively, it was demonstrated that concomitant administration of opioids was the significant factor of the incidence of somnolence and dizziness. The first onset date of the adverse effects was frequently detected in the early days of the pregabalin therapy. CONCLUSIONS: The fine tuning of pregabalin dosage schedule based on the renal function appeared to be critical for prevention of development of its adverse effects. Adverse effects tended to develop in the initial phase of pregabalin therapy. Concomitant administration of opioids with pregabalin has the potential to increase the incidence of adverse effects, and thus much more careful attention has to be paid especially in those situations. PMID- 26819742 TI - PK/PD analysis of biapenem in patients undergoing continuous hemodiafiltration. AB - BACKGROUND: Continuous hemodiafiltration (CHDF) is used as renal replacement therapy for critically ill patients with renal failure, and to treat hypercytokinemia. Since CHDF also clears therapeutic agents, drug pharmacokinetics (PK) should be dependent upon CHDF conditions. Although the antibiotic biapenem (BIPM) is used in patients undergoing CHDF, the optimal therapeutic regimen in such patients has not been fully clarified. In this study, we investigated the PK of BIPM in patients with various levels of renal function undergoing CHDF with polysulfone (PS) membrane, and used PK models to identify the optimal administration regimen. METHODS: BIPM (300 mg) was administered by infusion in patients undergoing CHDF (n = 7). Blood and filtrate-dialysate were collected for compartment and non-compartment analysis. RESULTS: The sieving coefficient of PS membrane was 1.00 +/- 0.06 (mean +/- S.D., n = 7), and CHDF clearance of BIPM was found to be the sum of the dialysate flow rate (QD) and filtrate flow rate (QF). Non-CHDF clearance showed inter-individual variability (4.82 +/- 2.48 L/h), depending on residual renal function and non-renal clearance. Based on the average PK parameters obtained with a compartmental model, maximal kill end point (over 40 % T > MIC4 MUg/mL) was achieved with regimens of 300 mg every 6 h, 300 mg every 8 h, and 600 mg every 12 h. Monte Carlo simulation indicated that 300 mg infusion for 1 h every 6 h was optimal, and the probability of target attainment at MIC2 MUg/mL was 90.2 %. CONCLUSIONS: Our results establish the optimal regimen of BIPM in patients with various levels of renal function undergoing CHDF with a PS membrane. PMID- 26819743 TI - Serum concentrations of clarithromycin and rifampicin in pulmonary Mycobacterium avium complex disease: long-term changes due to drug interactions and their association with clinical outcomes. AB - BACKGROUND: Concomitant use of clarithromycin (CAM) and rifampicin (RFP) for the treatment of pulmonary Mycobacterium avium complex (MAC) disease affects the systemic concentrations of both drugs due to CYP3A4-related interactions. To date, however, there has been no report that investigates the long-term relationship between the drug concentrations, CYP3A4 activity, and clinical outcomes. Our aim was to investigate the time course of the drug levels in long term treatment of subjects with pulmonary MAC disease, and examine the correlation of these concentrations with CYP3A4 activity and clinical outcomes. METHODS: Urine and blood samples from nine outpatients with pulmonary MAC disease were collected on days 1, 15, and 29 (for four subjects, sample collections were continued on days 57, 85, 113, 141, 169, 225, 281, 337, and 365). Serum drug concentrations and urinary levels of endogenous cortisol (F) and 6 beta hydroxycortisol (6betaOHF), the metabolite of F by CYP3A4, were measured, and evaluated 6betaOHF/F ratio as a CYP3A4 activity marker. In addition, the clinical outcomes of 4 subjects were evaluated based on examination of sputum cultures and chest images. RESULTS: The mean 6betaOHF/F ratio increased from 2.63 +/- 0.85 (n = 9) on the first day to 6.96 +/- 1.35 on day 15 and maintained a level more than double initial value thereafter. The serum CAM concentration decreased dramatically from an initial 2.28 +/- 0.61 MUg/mL to 0.73 +/- 0.23 MUg/mL on day 15. In contrast, the serum concentration of 14-hydroxy-CAM (M-5), the major metabolite of CAM, increased 2.4-fold by day 15. Thereafter, both CAM and M-5 concentrations remained constant until day 365. The explanation for the low levels of serum CAM in pulmonary MAC disease patients is that RFP-mediated CYP3A4 induction reached a maximum by day 15 and remained high thereafter. Sputum cultures of three of four subjects converted to negative, but relapse occurred in all three cases. CONCLUSIONS: Our study demonstrated that serum CAM concentrations in pulmonary MAC disease patients were continuously low because of RFP-mediated CYP3A4 induction, which may be responsible for the unsatisfactory clinical outcomes. PMID- 26819744 TI - Reduction in gastrointestinal bleeding by development and implementation of a protocol for stress ulcer prophylaxis: a before-after study. AB - BACKGROUND: The implementation of a protocol has been associated with improvements in the processes of care in clinical settings. Although stress ulcer prophylaxis is recommended for critically ill patients at high risk, there is currently no consensus on its use. Therefore, we herein developed a protocol for stress ulcer prophylaxis, and evaluated therapeutic outcomes in a before-after study. METHODS: The protocol was developed by considering the effectiveness, disadvantages (including adverse events) and cost of each agent based on previous findings. Patients who were admitted to the 8-bed emergency intensive care unit (ICU) of our hospital for more than 24 h during the year before and after implementation of the study were eligible. Each investigation item was evaluated retrospectively. RESULTS: There were 211 and 238 study patients before and after implementation of the protocol, respectively. The baseline characteristics of patients on/during ICU admission were similar in the two groups. The proportion of medicated patients was 79.6 % before and 84.5 % after protocol implementation. Before implementation of the protocol, 4.3 % of patients developed clinically important gastrointestinal bleeding, and this incidence decreased significantly to 0.8 % after its implementation (P = 0.019). The frequency at which medication was discontinued due to adverse events was slightly lower after implementation of the protocol. No significant differences were observed in the costs of stress ulcer prophylactic agents or mortality in the ICU. CONCLUSIONS: The results of the present study indicated that the development and implementation of a protocol for stress ulcer prophylaxis, for which there are currently no criteria, improved a main outcome, clinically important gastrointestinal bleeding. PMID- 26819745 TI - Analysis of the time-to-onset of osteonecrosis of jaw with bisphosphonate treatment using the data from a spontaneous reporting system of adverse drug events. AB - BACKGROUND: Bisphosphonates (BPs) are potent antiresorptive agents used to treat osteoporosis and the complications associated with malignant bone metastasis. The aim of this study was to evaluate the incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) using the Japanese Adverse Drug Event Report (JADER) database. In particular, we focused on the time-to-onset profile of BRONJ. FINDINGS: We analyzed reports of BRONJ in the JADER database and calculated the reporting odds ratio (ROR) of BPs potentially associated with BRONJ. We applied the weibull shape parameter to time-to-event data in JADER. The drugs selected for this investigation were seven BPs approved in Japan (alendronate [intraveneous, I.V.], pamidronate, and zoledronate as I.V. BPs; and alendronate (oral), etidronate, minodronate, and risedronate as oral BPs). We analyzed reports of BRONJ events associated with BPs in the JADER database from April 2004 to November 2014. The median value of BRONJ cases caused by alendronate (I.V.), pamidronate, zoledronate, alendronate (oral), etidronate, minodronate, and risedronate were 1342, 812, 486, 863, 1461, 432, and 730 days, respectively. The lower 95 % confidence interval of the Weibull-shape parameter beta for I.V. BPs (pamidronate and zoledronate) exceeded 1. The risk of BRONJ with I.V. BPs increased over time. CONCLUSION: Thus, the incidence of BRONJ with BP treatment should be closely monitored for a 3-year period. Further studies are required to draw conclusions, and we believe that this information about BRONJ induced by BPs will prove beneficial to patients and pharmacists. PMID- 26819746 TI - A laboratory data-based evaluation of the efficacy and safety of generic pravastatin sodium for long-term use. AB - BACKGROUND: Increasing the use of generic drugs may reduce the growing healthcare spending. Nevertheless, in Japan, the generic drug market share remains low compared to that of European countries and the United States, mainly because of the general distrust of generic drugs. To address this problem, we retrospectively evaluated the efficacy and safety of the long-term use of generic pravastatin sodium in a study from January 2008 to December 2011. METHODS: Patients receiving generic pravastatin sodium for >=15 months were defined as long-term users and were included in the study, totaling 595 out of 1337 patients. Efficacy assessment was based on the total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) plasma levels. Safety assessment was based on the aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK), gamma-glutamyl transferase (gamma-GTP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total-bilirubin (T-Bil), blood urea nitrogen (BUN), serum creatinine (Scr), and hemoglobin A1c (HbA1c) plasma levels. The patients' reasons for discontinuing generic pravastatin sodium were obtained from the electronic medical records. RESULTS & DISCUSSION: No significant difference in the laboratory data was observed between short-term and long-term users, except for significantly lower ALT levels in the long-term users than in the short-term users. No liver dysfunction was observed. Although 37 patients discontinued the study possibly owing to drug-related adverse events, we considered these events unrelated to generic pravastatin sodium. CONCLUSIONS: This study shows that the long-term use of generic pravastatin sodium is effective and safe, and may help dispel the concerns about generic drugs. PMID- 26819747 TI - Risk of major bleeding at different PT-INR ranges in elderly Japanese patients with non-valvular atrial fibrillation receiving warfarin: a nested case-control study. AB - BACKGROUND: Debate continues about the optimal anticoagulation level for elderly Japanese patients with non-valvular atrial fibrillation (NVAF) receiving warfarin. The Japanese Circulation Society guideline has recommended prothrombin time-international normalized ratios (PT-INR) of 1.6 - 2.6 for elderly patients and 2.0 - 3.0 for non-elderly patients, because previous observational studies indicated increased risk of bleeding when the ratio exceeded 2.6. We aimed to reappraise the relationship between PT-INR and the risk of major bleeding in elderly Japanese patients. METHODS: From the electronic medical records, we selected a cohort of elderly (age >= 70 years) Japanese patients with NVAF who were prescribed warfarin for the prevention of thromboembolic diseases between November 2010 and March 2014 at Kanto Rosai Hospital. We identified those who developed major bleeding (cases). For each case, we randomly selected two matched controls by adopting a risk-set sampling method defined by calendar date, age, gender, length of warfarin administration, and the prescriber of warfarin. The risk of major bleeding in patients having PT-INR <= 1.49, 1.50 - 1.99, 2.00 - 2.49 (the reference), 2.50 - 2.99, and >= 3.00 were compared using the conditional logistic regression method. The study protocol was approved by the IRB before the study was begun. RESULTS: Among the cohort of 806 elderly patients, we identified 32 cases and selected 64 matched controls. The overall incidence of major bleeding was 3.5 per 100 patient-years. The odds ratios (95 % confidence intervals) for the risk of developing major bleeding in patients with PT-INR <= 1.49 (n = 20), 1.50 - 1.99 (n = 32), 2.00 - 2.49 (n = 18), 2.50 - 2.99 (n = 10), and >= 3.00 (n = 16) were 1.0 (0.2, 5.9), 0.3 (0.1, 1.9), 1.0 (reference), 1.2 (0.2, 8.4), and 19.8 (2.0, 198.9), respectively, with a significant difference between >= 3.00 and reference. CONCLUSIONS: Among elderly Japanese patients with NVAF, PT-INR 2.0 - 3.0 may be associated with a clinically permissible risk of major bleeding while PT-INR >= 3.00 a significant risk. Further studies are warranted to determine whether the risk of major bleeding is significantly lower for PT-INR 2.50 - 2.99 than for PT-INR >= 3.00. PMID- 26819748 TI - Comparative effectiveness of biologic monotherapy versus combination therapy for patients with psoriatic arthritis: results from the Corrona registry. AB - OBJECTIVES: To characterise the comparative effectiveness of combination therapy (a tumour necrosis factor inhibitor (TNFi) and a conventional synthetic disease modifying antirheumatic drug (csDMARD) such as methotrexate) and monotherapy (TNFi only) for psoriatic arthritis (PsA) from a large US registry. METHODS: The analysis included adult patients with PsA who were enrolled in the Corrona database (ClinicalTrials.gov, NCT01402661), had initiated a TNFi, were biologic naive, and had a follow-up visit >=90 days after drug initiation. The endpoints of the analysis were TNFi persistence (drug survival) and time to Clinical Disease Activity Index (CDAI) remission. All analyses were performed using propensity scoring, which were estimated using CDAI and patient sex, to control for channelling bias. RESULTS: Of 519 patients meeting the inclusion criteria (318 with combination therapy and 201 with monotherapy), the analysis population was 497 for TNFi persistence and 380 for time to remission. The difference between combination therapy (TNFi+methotrexate, 91% of patients; TNFi+other csDMARD, 9%) and monotherapy was not statistically significant for TNFi persistence (32 and 31 months, p=0.73) and time to remission (21 and 25 months, p=0.56). Predictors of TNFi persistence included Hispanic ethnicity (longer persistence), PsA duration (longer persistence), history of methotrexate use (shorter persistence), body mass index (shorter persistence) and disease activity (shorter persistence). CONCLUSIONS: Patients with PsA from a large US registry experienced similar TNFi persistence on combination therapy and monotherapy. Prospective, randomised clinical trials evaluating the efficacy of combination therapy versus monotherapy would provide much-needed clarity on treatment options for patients with PsA. TRIAL REGISTRATION NUMBER: NCT01402661. PMID- 26819749 TI - Regulation of peripheral classical and non-classical monocytes on infliximab treatment in patients with rheumatoid arthritis and ankylosing spondylitis. AB - OBJECTIVE: To investigate the regulatory effect of tumour necrosis factor (TNF) blockade with infliximab on the distribution of peripheral blood monocyte subpopulations in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: Purified CD11b+CD14+ monocytes from 5 patients with RA and 5 AS were analysed ex vivo before and after infliximab treatment by flow cytometry for CD16, CD163, CD11b, C-C chemokine receptor type 2 (CCR2) and CXC chemokine receptor 4 (CXCR4) at baseline and at days 2, 14, 84 and 168 after the first infliximab administration. Serum levels of the stromal cell-derived factor (SDF)-1 and monocyte chemotactic peptide (MCP)-1 at different time points were measured in either patient group before and on infliximab treatment. RESULTS: Anti-TNF treatment with infliximab led to a significant increase of circulating CD11b+ non-classical and a concomitantly decrease of CD11b+ classical monocytes, to a decline in SDF-1 levels and reduced expression of CCR2 and CXCR4 on non classical monocyte subpopulation. CONCLUSIONS: Our study shows, that TNFalpha blockade by infliximab resulted in a dichotomy of the regulation of classical and non-classical monocytes that might have substantial impact on inhibition of osteoclastogenesis and of subsequent juxta-articular bone destruction and systemic bone loss in RA and AS. PMID- 26819750 TI - Suppression of arthritis-induced bone erosion by a CRAC channel antagonist. AB - OBJECTIVE: We have shown in vitro and in vivo that osteoclast maturation requires calcium-release activated calcium (CRAC) channels. In inflammatory arthritis, osteoclasts mediate severe and debilitating bone erosion. In the current study, we assess the value of CRAC channels as a therapeutic target to suppress bone erosion in acute inflammatory arthritis. METHODS: Collagen-induced arthritis (CIA) was induced in mice. The CRAC channel inhibitor 3,4-dichloropropionaniline (DCPA) and a placebo was administered 1 day prior to collagen II booster to induce arthritis. Effects on swelling, inflammatory cell invasion in joints, serum cytokines and bone erosion were measured. RESULTS: Assays, by blinded observers, of arthritis severity showed that DCPA, 21 mg/kg/day, suppressed arthritis development over 3 weeks. Bone and cartilage damage in sections of animal feet was reduced approximately 50%; overall swelling of joints was reduced by a similar amount. Effects on bone density by uCT showed clear separation in DCPA-treated CIA animals from CIA without treatment, while differences between controls without CIA and CIA treated with DCPA differed by small amounts and in most cases were not statistically different. Response was not related to anticollagen titres. There were no adverse effects in the treated group on animal weight or activity, consistent with low toxicity. The effect was maximal 12-17 days after collagen booster, during the rapid appearance of arthritis in untreated CIA. At 20 days after treatment (day 40), differences in arthritis score were reduced and tumour necrosis factor alpha, interleukin (IL)-1, or IL-6 in the serum of the animals were similar in treated and untreated animals. CONCLUSIONS: DCPA, a novel inhibitor of CRAC channels, suppresses bone erosion associated with acute arthritis in mice and might represent a new treatment modality for acute arthrits. PMID- 26819751 TI - Diagnostic impact of routine Lyme serology in recent-onset arthritis: results from the ESPOIR cohort. AB - OBJECTIVES: Lyme disease may be considered by rheumatologists in patients with recent-onset arthritis, even in the absence of suggestive symptoms. The aim of this study was to determine the diagnostic impact of routine Lyme serology in a French cohort of patients with recent-onset arthritis affecting at least 2 joints. METHODS: We performed an ancillary study of a French prospective multicentre cohort established to monitor clinical, biological and radiographic data in patients with inflammatory arthritis in at least 2 joints, lasting for 6 weeks to 6 months. Borrelia IgM and IgG antibodies were sought routinely at baseline, using ELISA tests, independently from the physician's strategy for detecting a spirochetal infection. We recorded the proportion of patients with a final diagnosis of Lyme arthritis and evaluated the diagnostic performance of Lyme serology in this particular context. The clinical and biological characteristics of patients according to the Lyme serology results were analysed. RESULTS: Of 810 patients, 657 (81.1%) were negative for IgM and IgG antibodies, 91 (11.2%) had only IgM antibodies, 49 (6%) had only IgG antibodies, and 13 (1.6%) had IgG and IgM antibodies. Thus, 7.6% had IgG positivity, consistent with exposure to Borrelia infection. IgG positivity was significantly more prevalent in the North and North-East regions of France (chi(2)=14.6, p<0.001). No patients received a definite diagnosis of Lyme arthritis. CONCLUSIONS: This study does not support routine Lyme serological testing in patients with recent-onset inflammatory arthritis affecting more than 1 joint. PMID- 26819752 TI - A multicentre, randomised, controlled, open-label pilot study on the feasibility of discontinuation of adalimumab in established patients with rheumatoid arthritis in stable clinical remission. AB - OBJECTIVES: Treatment with tumour necrosis factor (TNF) blockers, once started as therapy for rheumatoid arthritis (RA), is usually continued indefinitely. The aim of this trial was to assess the possibility of discontinuing treatment with adalimumab (ADA) while maintaining remission in patients with RA with established disease in stable remission on combination therapy with ADA and methotrexate (MTX). METHODS: In a randomised, controlled, open-label pilot study of patients with RA in stable remission treated with ADA+MTX, patients were randomised in a 1:1 ratio to continue with ADA plus MTX (arm AM) or MTX monotherapy (arm M) for 52 weeks. Flare was defined as Disease Activity Score (DAS28) >=2.6 or a change in DAS28 (DeltaDAS28) of >1.2 from baseline at any time. Patients in arm M with a flare restarted ADA. The primary end point was the proportion of patients in remission at week 28. RESULTS: 31 patients were enrolled in the study and randomised to arm AM (n=16) or arm M (n=15). At 28 weeks, 15/16 patients (94%) and 5/15 patients (33%) in arms AM and M, respectively, were in remission (p=0.001). During the first 28 weeks, 50% (8/16) in the AM arm and 80% (12/15) in the M arm had a flare (p=0.08). The number of patients in the AM and M arms with >=1 DeltaDAS28 >1.2 during the first 28 weeks was 1/16 (6%) and 8/15 (53%), respectively (p=0.005). CONCLUSIONS: In this study, remission was rarely maintained in patients with long-standing disease who discontinued ADA. Discontinuation may be feasible in only a minority of patients with established RA in stable clinical remission. TRIAL REGISTRATION NUMBER: NCT00808509. PMID- 26819753 TI - Long-term efficacy and safety of tocilizumab in giant cell arteritis and large vessel vasculitis. AB - Giant cell arteritis (GCA) is a chronic systemic vasculitis affecting large-sized and medium-sized vessels. Glucocorticoids are currently the mainstay of treatment for GCA and associated large vessel vasculitis (LVV) but are associated with frequent adverse events. Methotrexate has only demonstrated a modest benefit while anti-TNF biological agents (infliximab and etanercept) have been inefficacious. Elevated levels of interleukin-6 (IL-6), a proinflammatory cytokine, has been associated with GCA. Tocilizumab (TCZ), a humanised antihuman IL-6 receptor antibody, has been used successfully in several reports as a treatment for GCA and LVV. We report the potentially long-term successful use of TCZ in 8 cases of refractory LVV. All of our patients achieved a good clinical response to TCZ and C reactive protein reduced from an average of 70.3 to 2.5. In all cases, the glucocorticoid dose was reduced, from an average of 24.6 mg prednisolone prior to TCZ treatment to 4.7 mg, indicating that TCZ may enable a reduction in glucocorticoid-associated adverse events. However, regular TCZ administration was needed for disease control in most cases. TCZ was discontinued in one case due to the development of an empyema indicating the need for careful monitoring of infection when using this treatment. PMID- 26819754 TI - Clinical Management of Malignant Glaucoma. AB - Malignant glaucoma remains one of the most challenging complications of ocular surgery. Although it has been reported to occur spontaneously or after any ophthalmic procedure, it is most commonly encountered after glaucoma surgery in eyes with prior chronic angle closure. The clinical diagnosis is made in the setting of a patent peripheral iridotomy and axial flattening of the anterior chamber. Intraocular pressure is usually elevated, but it may be normal in some cases. Although the exact etiology of this condition is not fully understood, several mechanisms have been proposed and it is thought to result from posterior misdirection of aqueous humor into or behind the vitreous. This review discusses pathophysiology, differential diagnosis, imaging modalities, and current treatment strategies for this rare form of secondary glaucoma. PMID- 26819756 TI - The Interpretation of Dyspnea in the Patient with Asthma. AB - Physicians have noted dyspnea in severely ill asthmatic patients to be associated with fright or panic; in more stable patients dyspnea may reflect characteristics including lung function, personality and behavioral traits. This study evaluates the symptom of dyspnea in 32 asthmatic patients twice: first when acutely ill and again after an initial response to therapy. Spirometry was performed, dyspnea quantified (Borg scale), and panic assessed with a specialized measure of acute panic (the acute panic inventory (API)) in the 32 patients before and again after treatment. After treatment, questionnaires to evaluate somatization and panic disorder were also administered. When acutely ill, both the API and all spirometric measures (PEFR; FEV1; IC) correlated with dyspnea. Multiple linear regression showed that measures of the API, the peak expiratory flow rate, and female sex taken together accounted for 41% of dyspnea in acute asthma. After treatment, the API again predicted dyspnea while spirometric data did not. Those subjects who described themselves as having chronic panic disorder reported high grades of dyspnea after treatment also. We conclude that interpretations of the self-report of asthma differ between acutely ill and stable asthmatic patients. PMID- 26819757 TI - Comparative Analysis of the Properties of Acid-Base Indicator of Rose (Rosa setigera), Allamanda (Allamanda cathartica), and Hibiscus (Hibiscus rosa sinensis) Flowers. AB - The need to develop effective alternative for synthetic indicators is the demand of present-day chemistry. The acid-base indicator properties of Rose (Rosa setigera), Allamanda (Allamanda cathartica), and Hibiscus (Hibiscus rosa sinensis) flowers were examined. Colour pigments were extracted from the flowers via cold and solvent extraction using soxhlet extractor. The pH value of the extracts with wavelengths of absorption was determined using ultraviolet spectrophotometer. From the results obtained, all the extracts exhibited sharp contrast between their colours in acid and base. Their pH was found to be 5.5 for cold extract of Rose and 5.6 for solvent extraction, 5.24 for cold extract of a Hibiscus and 6.52 for solvent extraction, 5.35 for cold extract of Allamanda, and 5.45 for solvent extraction. The maximum wavelengths of absorption obtained for all the extract fall within the visible region of electromagnetic spectrum. These values are almost similar to that obtained from synthetic indicators. It is on these bases that we concluded that natural indicators could be an excellent replacement for synthetic indicators since they are cheap, readily available, simple to extract, not toxic, user and environmentally friendly. PMID- 26819755 TI - Lutein, Zeaxanthin, and meso-Zeaxanthin in the Clinical Management of Eye Disease. AB - Lutein, zeaxanthin, and meso-zeaxanthin are xanthophyll carotenoids found within the retina and throughout the visual system. The retina is one of the most metabolically active tissues in the body. The highest concentration of xanthophylls is found within the retina, and this selective presence has generated many theories regarding their role in supporting retinal function. Subsequently, the effect of xanthophylls in the prevention and treatment of various eye diseases has been examined through epidemiological studies, animal studies, and clinical trials. This paper attempts to review the epidemiological studies and clinical trials investigating the effects of xanthophylls on the incidence and progression of various eye diseases. Observational studies have reported that increased dietary intake and higher serum levels of lutein and zeaxanthin are associated with lower risk of age-related macular degeneration (AMD), especially late AMD. Randomized, placebo-controlled clinical trials have demonstrated that xanthophyll supplementation increases macular pigment levels, improves visual function, and decreases the risk of progression to late AMD, especially neovascular AMD. Current publications on the preventive and therapeutic effects of lutein and zeaxanthin on cataracts, diabetic retinopathy, and retinopathy of prematurity have reported encouraging results. PMID- 26819759 TI - Endemicity of Acinetobacter calcoaceticus-baumannii Complex in an Intensive Care Unit in Malaysia. AB - Introduction. Acinetobacter calcoaceticus-baumannii complex (ACB complex) is a leading opportunistic pathogen in intensive care units (ICUs). Effective control of spread requires understanding of its epidemiological relatedness. This study aims to determine the genetic relatedness and antibiotic susceptibilities of ACB complex in an ICU in Malaysia. Methodology. Pulsed field gel electrophoresis (PFGE), E-test, and disk diffusion were used for isolates characterization. Results. During the study period (December 2011 to June 2012), 1023 patients were admitted to the ICU and 44 ACB complex (blood, n = 21, and blind bronchial aspirates, n = 23) were recovered from 38 ICU patients. Six isolates were from non-ICU patients. Of the 44 ICU isolates, 88.6% exhibited multidrug-resistant (MDR) patterns. There was high degree of resistance, with minimum inhibitory concentration90 (MIC90) of >32 MUg/mL for carbapenems and >=256 MUg/mL for amikacin, ampicillin/sulbactam, and cefoperazone/sulbactam. Isolates from the main PFGE cluster were highly resistant. There was evidence of dissemination in non-ICU wards. Conclusion. High number of clonally related MDR ACB complex was found. While the ICU is a likely reservoir facilitating transmission, importation from other wards may be important contributor. Early identification of strain relatedness and implementation of infection control measures are necessary to prevent further spread. PMID- 26819758 TI - Reassessing the Role of Intra-Arterial Drug Delivery for Glioblastoma Multiforme Treatment. AB - Effective treatment for glioblastoma (GBM) will likely require targeted delivery of several specific pharmacological agents simultaneously. Intra-arterial (IA) delivery is one technique for targeting the tumor site with multiple agents. Although IA chemotherapy for glioblastoma (GBM) has been attempted since the 1950s, the predicted benefits remain unproven in clinical practice. This review focuses on innovative approaches to IA drug delivery in treating GBM. Guided by novel in vitro and in vivo optical measurements, newer pharmacokinetic models promise to better define the complex relationship between background cerebral blood flow and drug injection parameters. Advanced optical technologies and tracers, unique nanoparticles designs, new cellular targets, and rational drug formulations are continuously modifying the therapeutic landscape for GBM. Personalized treatment approaches are emerging; however, such tailored approaches will largely depend on effective drug delivery techniques and on the ability to simultaneously deliver multidrug regimens. These new paradigms for tumor selective drug delivery herald dramatic improvements in the effectiveness of IA chemotherapy for GBM. Therefore, within this context of so-called "precision medicine," the role of IA delivery for GBM is thoroughly reassessed. PMID- 26819760 TI - TRPV1 and PLC Participate in Histamine H4 Receptor-Induced Itch. AB - Histamine H4 receptor has been confirmed to play a role in evoking peripheral pruritus. However, the ionic and intracellular signaling mechanism of activation of H4 receptor on the dorsal root ganglion (DRG) neurons is still unknown. By using cell culture and calcium imaging, we studied the underlying mechanism of activation of H4 receptor on the DRG neuron. Immepip dihydrobromide (immepip)-a histamine H4 receptor special agonist under cutaneous injection-obviously induced itch behavior of mice. Immepip-induced scratching behavior could be blocked by TRPV1 antagonist AMG9810 and PLC pathway inhibitor U73122. Application of immepip (8.3-50 MUM) could also induce a dose-dependent increase in intracellular Ca(2+) ([Ca(2+)]i) of DRG neurons. We found that 77.8% of the immepip-sensitized DRG neurons respond to the TRPV1 selective agonist capsaicin. U73122 could inhibit immepip-induced Ca(2+) responses. In addition, immepip-induced [Ca(2+)]i increase could be blocked by ruthenium red, capsazepine, and AMG9810; however it could not be blocked by TRPA1 antagonist HC-030031. These results indicate that TRPV1 but not TRPA1 is the important ion channel to induce the DRG neurons' responses in the downstream signaling pathway of histamine H4 receptor and suggest that TRPV1 may be involved in the mechanism of histamine-induced itch response by H4 receptor activation. PMID- 26819761 TI - Bilateral Neuropathy of Primary Sensory Neurons by the Chronic Compression of Multiple Unilateral DRGs. AB - To mimic multilevel nerve root compression and intervertebral foramina stenosis in human, we established a new animal model of the chronic compression of unilateral multiple lumbar DRGs (mCCD) in the rat. A higher occurrence of signs of spontaneous pain behaviors, such as wet-dog shaking and spontaneous hind paw shrinking behaviors, was firstly observed from day 1 onward. In the meantime, the unilateral mCCD rat exhibited significant bilateral hind paw mechanical and cold allodynia and hyperalgesia, as well as a thermal preference to 30 degrees C plate between 30 and 35 degrees C. The expression of activating transcription factor 3 (ATF3) was significantly increased in the ipsilateral and contralateral all-sized DRG neurons after the mCCD. And the expression of CGRP was significantly increased in the ipsilateral and contralateral large- and medium-sized DRG neurons. ATF3 and CGRP expressions correlated to evoked pain hypersensitivities such as mechanical and cold allodynia on postoperative day 1. The results suggested that bilateral neuropathy of primary sensory neurons might contribute to bilateral hypersensitivity in the mCCD rat. PMID- 26819762 TI - Behavioral Deficits in Juveniles Mediated by Maternal Stress Hormones in Mice. AB - Maternal depression has been shown to negatively impact offspring development. Investigation into the impact of maternal depression and offspring behavior has relied on correlative studies in humans. Further investigation into the underlying mechanisms has been hindered by the lack of useful animal models. We previously characterized a mouse model which exhibits depression-like behaviors restricted to the postpartum period and abnormal/fragmented maternal care (Gabrd (-/-) mice). Here we utilized this unique mouse model to investigate the mechanism(s) through which maternal depression-like behaviors adversely impact offspring development. Cross-fostering experiments reveal increased anxiety-like and depression-like behaviors in mice reared by Gabrd (-/-) mothers. Wild type and Gabrd (-/-) mice subjected to unpredictable stress during late pregnancy exhibit decreased pup survival and depression-like behavior in the postpartum period. Exogenous corticosterone treatment in wild type mice during late pregnancy is sufficient to decrease pup survival and induce anxiety-like and depression-like behaviors in the offspring. Further, the abnormal behaviors in juvenile mice reared by Gabrd (-/-) mice are alleviated by treatment of the mothers with the corticotropin-releasing hormone (CRH) antagonist, Antalarmin. These studies suggest that hyperresponsiveness of the HPA axis is associated with postpartum depression and may mediate the adverse effects of maternal depression on offspring behavior. PMID- 26819764 TI - Bilingualism and Musicianship Enhance Cognitive Control. AB - Learning how to speak a second language (i.e., becoming a bilingual) and learning how to play a musical instrument (i.e., becoming a musician) are both thought to increase executive control through experience-dependent plasticity. However, evidence supporting this effect is mixed for bilingualism and limited for musicianship. In addition, the combined effects of bilingualism and musicianship on executive control are unknown. To determine whether bilingualism, musicianship, and combined bilingualism and musicianship improve executive control, we tested 219 young adults belonging to one of four groups (bilinguals, musicians, bilingual musicians, and controls) on a nonlinguistic, nonmusical, visual-spatial Simon task that measured the ability to ignore an irrelevant and misinformative cue. Results revealed that bilinguals, musicians, and bilingual musicians showed an enhanced ability to ignore a distracting cue relative to controls, with similar levels of superior performance among bilinguals, musicians, and bilingual musicians. These results indicate that bilingualism and musicianship improve executive control and have implications for educational and rehabilitation programs that use music and foreign language instruction to boost cognitive performance. PMID- 26819765 TI - Compensation through Functional Hyperconnectivity: A Longitudinal Connectome Assessment of Mild Traumatic Brain Injury. AB - Mild traumatic brain injury (mTBI) is a major public health concern. Functional MRI has reported alterations in several brain networks following mTBI. However, the connectome-scale brain network changes are still unknown. In this study, sixteen mTBI patients were prospectively recruited from an emergency department and followed up at 4-6 weeks after injury. Twenty-four healthy controls were also scanned twice with the same time interval. Three hundred fifty-eight brain landmarks that preserve structural and functional correspondence of brain networks across individuals were used to investigate longitudinal brain connectivity. Network-based statistic (NBS) analysis did not find significant difference in the group-by-time interaction and time effects. However, 258 functional pairs show group differences in which mTBI patients have higher functional connectivity. Meta-analysis showed that "Action" and "Cognition" are the most affected functional domains. Categorization of connectomic signatures using multiview group-wise cluster analysis identified two patterns of functional hyperconnectivity among mTBI patients: (I) between the posterior cingulate cortex and the association areas of the brain and (II) between the occipital and the frontal lobes of the brain. Our results demonstrate that brain concussion renders connectome-scale brain network connectivity changes, and the brain tends to be hyperactivated to compensate the pathophysiological disturbances. PMID- 26819763 TI - Reorganization of Synaptic Connections and Perineuronal Nets in the Deep Cerebellar Nuclei of Purkinje Cell Degeneration Mutant Mice. AB - The perineuronal net (PN) is a subtype of extracellular matrix appearing as a net like structure around distinct neurons throughout the whole CNS. PNs surround the soma, proximal dendrites, and the axonal initial segment embedding synaptic terminals on the neuronal surface. Different functions of the PNs are suggested which include support of synaptic stabilization, inhibition of axonal sprouting, and control of neuronal plasticity. A number of studies provide evidence that removing PNs or PN-components results in renewed neurite growth and synaptogenesis. In a mouse model for Purkinje cell degeneration, we examined the effect of deafferentation on synaptic remodeling and modulation of PNs in the deep cerebellar nuclei. We found reduced GABAergic, enhanced glutamatergic innervations at PN-associated neurons, and altered expression of the PN components brevican and hapln4. These data refer to a direct interaction between ECM and synapses. The altered brevican expression induced by activated astrocytes could be required for an adequate regeneration by promoting neurite growth and synaptogenesis. PMID- 26819766 TI - Cross-Modal Functional Reorganization of Visual and Auditory Cortex in Adult Cochlear Implant Users Identified with fNIRS. AB - Cochlear implant (CI) users show higher auditory-evoked activations in visual cortex and higher visual-evoked activation in auditory cortex compared to normal hearing (NH) controls, reflecting functional reorganization of both visual and auditory modalities. Visual-evoked activation in auditory cortex is a maladaptive functional reorganization whereas auditory-evoked activation in visual cortex is beneficial for speech recognition in CI users. We investigated their joint influence on CI users' speech recognition, by testing 20 postlingually deafened CI users and 20 NH controls with functional near-infrared spectroscopy (fNIRS). Optodes were placed over occipital and temporal areas to measure visual and auditory responses when presenting visual checkerboard and auditory word stimuli. Higher cross-modal activations were confirmed in both auditory and visual cortex for CI users compared to NH controls, demonstrating that functional reorganization of both auditory and visual cortex can be identified with fNIRS. Additionally, the combined reorganization of auditory and visual cortex was found to be associated with speech recognition performance. Speech performance was good as long as the beneficial auditory-evoked activation in visual cortex was higher than the visual-evoked activation in the auditory cortex. These results indicate the importance of considering cross-modal activations in both visual and auditory cortex for potential clinical outcome estimation. PMID- 26819767 TI - The Athlete's Brain: Cross-Sectional Evidence for Neural Efficiency during Cycling Exercise. AB - The "neural efficiency" hypothesis suggests that experts are characterized by a more efficient cortical function in cognitive tests. Although this hypothesis has been extended to a variety of movement-related tasks within the last years, it is unclear whether or not neural efficiency is present in cyclists performing endurance exercise. Therefore, this study examined brain cortical activity at rest and during exercise between cyclists of higher (HIGH; n = 14; 55.6 +/- 2.8 mL/min/kg) and lower (LOW; n = 15; 46.4 +/- 4.1 mL/min/kg) maximal oxygen consumption (VO2MAX). Male and female participants performed a graded exercise test with spirometry to assess VO2MAX. After 3 to 5 days, EEG was recorded at rest with eyes closed and during cycling at the individual anaerobic threshold over a 30 min period. Possible differences in alpha/beta ratio as well as alpha and beta power were investigated at frontal, central, and parietal sites. The statistical analysis revealed significant differences between groups (F = 12.04; p = 0.002), as the alpha/beta ratio was increased in HIGH compared to LOW in both the resting state (p <= 0.018) and the exercise condition (p <= 0.025). The present results indicate enhanced neural efficiency in subjects with high VO2MAX, possibly due to the inhibition of task-irrelevant cognitive processes. PMID- 26819768 TI - Closely Spaced MEG Source Localization and Functional Connectivity Analysis Using a New Prewhitening Invariance of Noise Space Algorithm. AB - This paper proposed a prewhitening invariance of noise space (PW-INN) as a new magnetoencephalography (MEG) source analysis method, which is particularly suitable for localizing closely spaced and highly correlated cortical sources under real MEG noise. Conventional source localization methods, such as sLORETA and beamformer, cannot distinguish closely spaced cortical sources, especially under strong intersource correlation. Our previous work proposed an invariance of noise space (INN) method to resolve closely spaced sources, but its performance is seriously degraded under correlated noise between MEG sensors. The proposed PW INN method largely mitigates the adverse influence of correlated MEG noise by projecting MEG data to a new space defined by the orthogonal complement of dominant eigenvectors of correlated MEG noise. Simulation results showed that PW INN is superior to INN, sLORETA, and beamformer in terms of localization accuracy for closely spaced and highly correlated sources. Lastly, source connectivity between closely spaced sources can be satisfactorily constructed from source time courses estimated by PW-INN but not from results of other conventional methods. Therefore, the proposed PW-INN method is a promising MEG source analysis to provide a high spatial-temporal characterization of cortical activity and connectivity, which is crucial for basic and clinical research of neural plasticity. PMID- 26819769 TI - The Involvement of Neuron-Specific Factors in Dendritic Spinogenesis: Molecular Regulation and Association with Neurological Disorders. AB - Dendritic spines are the location of excitatory synapses in the mammalian nervous system and are neuron-specific subcellular structures essential for neural circuitry and function. Dendritic spine morphology is determined by the F-actin cytoskeleton. F-actin remodeling must coordinate with different stages of dendritic spinogenesis, starting from dendritic filopodia formation to the filopodia-spines transition and dendritic spine maturation and maintenance. Hundreds of genes, including F-actin cytoskeleton regulators, membrane proteins, adaptor proteins, and signaling molecules, are known to be involved in regulating synapse formation. Many of these genes are not neuron-specific, but how they specifically control dendritic spine formation in neurons is an intriguing question. Here, we summarize how ubiquitously expressed genes, including syndecan 2, NF1 (encoding neurofibromin protein), VCP, and CASK, and the neuron-specific gene CTTNBP2 coordinate with neurotransmission, transsynaptic signaling, and cytoskeleton rearrangement to control dendritic filopodia formation, filopodia spines transition, and dendritic spine maturation and maintenance. The aforementioned genes have been associated with neurological disorders, such as autism spectrum disorders (ASDs), mental retardation, learning difficulty, and frontotemporal dementia. We also summarize the corresponding disorders in this report. PMID- 26819770 TI - Phosphorylation of CRMP2 by Cdk5 Regulates Dendritic Spine Development of Cortical Neuron in the Mouse Hippocampus. AB - Proper density and morphology of dendritic spines are important for higher brain functions such as learning and memory. However, our knowledge about molecular mechanisms that regulate thedevelopment and maintenance of dendritic spines is limited. We recently reported that cyclin-dependent kinase 5 (Cdk5) is required for the development and maintenance of dendritic spines of cortical neurons in the mouse brain. Previous in vitro studies have suggested the involvement of Cdk5 substrates in the formation of dendritic spines; however, their role in spine development has not been tested in vivo. Here, we demonstrate that Cdk5 phosphorylates collapsin response mediator protein 2 (CRMP2) in the dendritic spines of cultured hippocampal neurons and in vivo in the mouse brain. When we eliminated CRMP2 phosphorylation in CRMP2(KI/KI) mice, the densities of dendritic spines significantly decreased in hippocampal CA1 pyramidal neurons in the mouse brain. These results indicate that phosphorylation of CRMP2 by Cdk5 is important for dendritic spine development in cortical neurons in the mouse hippocampus. PMID- 26819771 TI - Influence of Genetic Variants of the N-Methyl-D-Aspartate Receptor on Emotion and Social Behavior in Adolescents. AB - Considerable evidence has suggested that the epigenetic regulation of N-methyl-D aspartate (NMDA) glutamate receptors plays a crucial role in neuropsychiatric disorders. Previous exploratory studies have been primarily based on evidence from patients and have rarely sampled the general population. This exploratory study examined the relationship of single-nucleotide polymorphism (SNP) variations in the genes encoding the NMDA receptor (i.e., GRIN1, GRIN2A, GRIN2B, GRIN2C, and GRIN2D) with emotion and social behavior in adolescents. For this study, 832 tenth-grade Taiwanese volunteers were recruited, and their scores from the Beck Youth Inventories were used to evaluate their emotional and social impairments. Based on these scores, GRIN1 (rs4880213) was significantly associated with depression and disruptive behavior. In addition, GRIN2B (rs7301328) was significantly associated with disruptive behavior. Because emotional and social impairment greatly influence learning ability, the findings of this study provide important information for clinical treatment and the development of promising prevention and treatment strategies, especially in the area of psychological adjustment. PMID- 26819772 TI - Acute Psychological Stress Modulates the Expression of Enzymes Involved in the Kynurenine Pathway throughout Corticolimbic Circuits in Adult Male Rats. AB - Tryptophan is an essential dietary amino acid that is necessary for protein synthesis, but also serves as the precursor for serotonin. However, in addition to these biological functions, tryptophan also serves as a precursor for the kynurenine pathway, which has neurotoxic (quinolinic acid) and neuroprotective (kynurenic acid) metabolites. Glucocorticoid hormones and inflammatory mediators, both of which are increased by stress, have been shown to bias tryptophan along the kynurenine pathway and away from serotonin synthesis; however, to date, there is no published data regarding the effects of stress on enzymes regulating the kynurenine pathway in a regional manner throughout the brain. Herein, we examined the effects of an acute psychological stress (120 min restraint) on gene expression patterns of enzymes along the kynurenine pathway over a protracted time-course (1-24 h post-stress termination) within the amygdala, hippocampus, hypothalamus, and medial prefrontal cortex. Time-dependent changes in differential enzymes along the kynurenine metabolism pathway, particularly those involved in the production of quinolinic acid, were found within the amygdala, hypothalamus, and medial prefrontal cortex, with no changes seen in the hippocampus. These regional differences acutely may provide mechanistic insight into processes that become dysregulated chronically in stress-associated disorders. PMID- 26819773 TI - A High-Fat Diet Causes Impairment in Hippocampal Memory and Sex-Dependent Alterations in Peripheral Metabolism. AB - While high-fat diets are associated with rising incidence of obesity/type-2 diabetes and can induce metabolic and cognitive deficits, sex-dependent comparisons are rarely systematically made. Effects of exclusive consumption of a high-fat diet (HFD) on systemic metabolism and on behavioral measures of hippocampal-dependent memory were compared in young male and female LE rats. Littermates were fed from weaning either a HFD or a control diet (CD) for 12 wk prior to testing. Sex-different effects of the HFD were observed in classic metabolic signs associated with type-2 diabetes. Males fed the HFD became obese, and had elevated fasted blood glucose levels, elevated corticosterone, and impaired glucose-tolerance, while females on the HFD exhibited only elevated corticosterone. Regardless of peripheral metabolism alteration, rats of both sexes fed the HFD were equally impaired in a spatial object recognition memory task associated with impaired hippocampal function. While the metabolic changes reported here have been characterized previously in males, the set of diet induced effects observed here in females are novel. Impaired memory can have significant cognitive consequences, over the short-term and over the lifespan. A significant need exists for comparative research into sex-dependent differences underlying obesity and metabolic syndromes relating systemic, cognitive, and neural plasticity mechanisms. PMID- 26819774 TI - Deep Brain Stimulation for Obesity: From a Theoretical Framework to Practical Application. AB - Obesity remains a pervasive global health problem. While there are a number of nonsurgical and surgical options for treatment, the incidence of obesity continues to increase at an alarming rate. The inability to curtail the growing rise of the obesity epidemic may be related to a combination of increased food availability and palatability. Research into feeding behavior has yielded a number of insights into the homeostatic and reward mechanisms that govern feeding. However, there remains a gap between laboratory investigations of feeding physiology in animals and translation into meaningful treatment options for humans. In addition, laboratory investigation may not be able to recapitulate all aspects of human food consumption. In a landmark pilot study of deep brain stimulation (DBS) of the lateral hypothalamic area for obesity, we found that there was an increase in resting metabolic rate as well as a decreased urge to eat. In this review, the authors will review some of the work relating to feeding physiology and research surrounding two nodes involved in feeding homeostasis, nucleus accumbens (NAc) and hypothalamus, and use this to provide a framework for future investigations of DBS as a viable therapeutic modality for obesity. PMID- 26819775 TI - EEG Radiotelemetry in Small Laboratory Rodents: A Powerful State-of-the Art Approach in Neuropsychiatric, Neurodegenerative, and Epilepsy Research. AB - EEG radiotelemetry plays an important role in the neurological characterization of transgenic mouse models of neuropsychiatric and neurodegenerative diseases as well as epilepsies providing valuable insights into underlying pathophysiological mechanisms and thereby facilitating the development of new translational approaches. We elaborate on the major advantages of nonrestraining EEG radiotelemetry in contrast to restraining procedures such as tethered systems or jacket systems containing recorders. Whereas a main disadvantage of the latter is their unphysiological, restraining character, telemetric EEG recording overcomes these disadvantages. It allows precise and highly sensitive measurement under various physiological and pathophysiological conditions. Here we present a detailed description of a straightforward successful, quick, and efficient technique for intraperitoneal as well as subcutaneous pouch implantation of a standard radiofrequency transmitter in mice and rats. We further present computerized 3D-stereotaxic placement of both epidural and deep intracerebral electrodes. Preoperative preparation of mice and rats, suitable anaesthesia, and postoperative treatment and pain management are described in detail. A special focus is on fields of application, technical and experimental pitfalls, and technical connections of commercially available radiotelemetry systems with other electrophysiological setups. PMID- 26819776 TI - The Exercising Brain: Changes in Functional Connectivity Induced by an Integrated Multimodal Cognitive and Whole-Body Coordination Training. AB - This study investigated the impact of "life kinetik" training on brain plasticity in terms of an increased functional connectivity during resting-state functional magnetic resonance imaging (rs-fMRI). The training is an integrated multimodal training that combines motor and cognitive aspects and challenges the brain by introducing new and unfamiliar coordinative tasks. Twenty-one subjects completed at least 11 one-hour-per-week "life kinetik" training sessions in 13 weeks as well as before and after rs-fMRI scans. Additionally, 11 control subjects with 2 rs-fMRI scans were included. The CONN toolbox was used to conduct several seed-to voxel analyses. We searched for functional connectivity increases between brain regions expected to be involved in the exercises. Connections to brain regions representing parts of the default mode network, such as medial frontal cortex and posterior cingulate cortex, did not change. Significant connectivity alterations occurred between the visual cortex and parts of the superior parietal area (BA7). Premotor area and cingulate gyrus were also affected. We can conclude that the constant challenge of unfamiliar combinations of coordination tasks, combined with visual perception and working memory demands, seems to induce brain plasticity expressed in enhanced connectivity strength of brain regions due to coactivation. PMID- 26819778 TI - History of Illicit Stimulant Use Is Not Associated with Long-Lasting Changes in Learning of Fine Motor Skills in Humans. AB - Little is known about the long-lasting effect of use of illicit stimulant drugs on learning of new motor skills. We hypothesised that abstinent individuals with a history of primarily methamphetamine and ecstasy use would exhibit normal learning of a visuomotor tracking task compared to controls. The study involved three groups: abstinent stimulant users (n = 21; 27 +/- 6 yrs) and two gender matched control groups comprising nondrug users (n = 16; 22 +/- 4 yrs) and cannabis users (n = 16; 23 +/- 5 yrs). Motor learning was assessed with a three minute visuomotor tracking task. Subjects were instructed to follow a moving target on a computer screen with movement of the index finger. Metacarpophalangeal joint angle and first dorsal interosseous electromyographic activity were recorded. Pattern matching was assessed by cross-correlation of the joint angle and target traces. Distance from the target (tracking error) was also calculated. Motor learning was evident in the visuomotor task. Pattern matching improved over time (cross-correlation coefficient) and tracking error decreased. However, task performance did not differ between the groups. The results suggest that learning of a new fine visuomotor skill is unchanged in individuals with a history of illicit stimulant use. PMID- 26819777 TI - Taking Sides: An Integrative Review of the Impact of Laterality and Polarity on Efficacy of Therapeutic Transcranial Direct Current Stimulation for Anomia in Chronic Poststroke Aphasia. AB - Anomia is a frequent and persistent symptom of poststroke aphasia, resulting from damage to areas of the brain involved in language production. Cortical neuroplasticity plays a significant role in language recovery following stroke and can be facilitated by behavioral speech and language therapy. Recent research suggests that complementing therapy with neurostimulation techniques may enhance functional gains, even amongst those with chronic aphasia. The current review focuses on the use of transcranial Direct Current Stimulation (tDCS) as an adjunct to naming therapy for individuals with chronic poststroke aphasia. Our survey of the literature indicates that combining therapy with anodal (excitatory) stimulation to the left hemisphere and/or cathodal (inhibitory) stimulation to the right hemisphere can increase both naming accuracy and speed when compared to the effects of therapy alone. However, the benefits of tDCS as a complement to therapy have not been yet systematically investigated with respect to site and polarity of stimulation. Recommendations for future research to help determine optimal protocols for combined therapy and tDCS are outlined. PMID- 26819780 TI - Effect of Associative Learning on Memory Spine Formation in Mouse Barrel Cortex. AB - Associative fear learning, in which stimulation of whiskers is paired with mild electric shock to the tail, modifies the barrel cortex, the functional representation of sensory receptors involved in the conditioning, by inducing formation of new inhibitory synapses on single-synapse spines of the cognate barrel hollows and thus producing double-synapse spines. In the barrel cortex of conditioned, pseudoconditioned, and untreated mice, we analyzed the number and morphological features of dendritic spines at various maturation and stability levels: sER-free spines, spines containing smooth endoplasmic reticulum (sER), and spines containing spine apparatus. Using stereological analysis of serial sections examined by transmission electron microscopy, we found that the density of double-synapse spines containing spine apparatus was significantly increased in the conditioned mice. Learning also induced enhancement of the postsynaptic density area of inhibitory synapses as well as increase in the number of polyribosomes in such spines. In single-synapse spines, the effects of conditioning were less pronounced and included increase in the number of polyribosomes in sER-free spines. The results suggest that fear learning differentially affects single- and double-synapse spines in the barrel cortex: it promotes maturation and stabilization of double-synapse spines, which might possibly contribute to permanent memory formation, and upregulates protein synthesis in single-synapse spines. PMID- 26819779 TI - CB2 Cannabinoid Receptor Knockout in Mice Impairs Contextual Long-Term Memory and Enhances Spatial Working Memory. AB - Neurocognitive effects of cannabinoids have been extensively studied with a focus on CB1 cannabinoid receptors because CB1 receptors have been considered the major cannabinoid receptor in the nervous system. However, recent discoveries of CB2 cannabinoid receptors in the brain demand accurate determination of whether and how CB2 receptors are involved in the cognitive effects of cannabinoids. CB2 cannabinoid receptors are primarily involved in immune functions, but also implicated in psychiatric disorders such as schizophrenia and depression. Here, we examined the effects of CB2 receptor knockout in mice on memory to determine the roles of CB2 receptors in modulating cognitive function. Behavioral assays revealed that hippocampus-dependent, long-term contextual fear memory was impaired whereas hippocampus-independent, cued fear memory was normal in CB2 receptor knockout mice. These mice also displayed enhanced spatial working memory when tested in a Y-maze. Motor activity and anxiety of CB2 receptor knockout mice were intact when assessed in an open field arena and an elevated zero maze. In contrast to the knockout of CB2 receptors, acute blockade of CB2 receptors by AM603 in C57BL/6J mice had no effect on memory, motor activity, or anxiety. Our results suggest that CB2 cannabinoid receptors play diverse roles in regulating memory depending on memory types and/or brain areas. PMID- 26819782 TI - Ruptured Sinus of Valsalva Aneurysm into the Left Atrium with Multiple Fistulous Communications: A Rare Cause of Heart Failure. AB - Ruptured noncoronary sinus of valsalva aneurysm with fistulous connections to multiple cardiac chambers has not been reported previously. We report a 66-year old man who presented with worsening cough and exertional dyspnea. Transesophageal echocardiogram confirmed a large aneurysm involving the noncoronary cusp of the aortic sinus with aneurysmal extension to the left atrium. There were also two fistulous communications with the left atrium and one small fistulous connection with the right atrium. Open-heart surgery with aortic root replacement and reimplantation of coronary arteries along with primary closure and repair of aorta to the left atrial fistula was performed. PMID- 26819781 TI - Functional Reorganizations of Brain Network in Prelingually Deaf Adolescents. AB - Previous neuroimaging studies suggested structural or functional brain reorganizations occurred in prelingually deaf subjects. However, little is known about the reorganizations of brain network architectures in prelingually deaf adolescents. The present study aims to investigate alterations of whole-brain functional network using resting-state fMRI and graph theory analysis. We recruited 16 prelingually deaf adolescents (10~18 years) and 16 normal controls matched in age and gender. Brain networks were constructed from mean time courses of 90 regions. Widely distributed network was observed in deaf subjects, with increased connectivity between the limbic system and regions involved in visual and language processing, suggesting reinforcement of the processing for the visual and verbal information in deaf adolescents. Decreased connectivity was detected between the visual regions and language regions possibly due to inferior reading or speaking skills in deaf subjects. Using graph theory analysis, we demonstrated small-worldness property did not change in prelingually deaf adolescents relative to normal controls. However, compared with healthy adolescents, eight regions involved in visual, language, and auditory processing were identified as hubs only present in prelingually deaf adolescents. These findings revealed reorganization of brain functional networks occurred in prelingually deaf adolescents to adapt to deficient auditory input. PMID- 26819783 TI - Rare Occurrence of Herpes Zoster of Trigeminal Nerve following Extraction of Tooth. AB - Herpes Zoster also known as Shingles is an acute viral infection which is an extremely painful and incapacitating ailment. It results from the reactivation of the varicella zoster virus. The triggering factors for the onset of an attack of Herpes Zoster include some form of immunosuppression. The diagnosis of Herpes Zoster can be made on proper medical history and a thorough clinical examination. Here is the report of a male patient affected by Herpes Zoster infection which followed after extraction of a lower first molar. PMID- 26819784 TI - Idiopathic Thrombocytopenic Purpura Misdiagnosed as Hereditary Angioedema. AB - Hereditary angioedema is a rare, but potentially life-threatening genetic disorder that results from an autosomal dominant trait. It is characterized by acute, recurrent attacks of severe local edema, most commonly affecting the skin and mucosa. Swelling in hereditary angioedema patients does however not always have to be caused by angioedema but can relate to other concomitant disorders. In this report we are focusing on misdiagnosis in a patient with known hereditary angioedema, whose bleeding episode caused by idiopathic thrombocytopenic purpura was mistaken for an acute attack of hereditary angioedema. The case illustrates how clinicians can have difficulties in handling patients with rare diseases, especially in the emergency care setting. PMID- 26819785 TI - Life-Threatening Retropharyngeal Hemorrhage Secondary to Rupture of the Inferior Thyroid Artery. AB - Inferior thyroid artery (ITA) rupture is rare and may progress to life threatening conditions. We present a patient who visited the emergency department after an episode of syncope and dizziness in which he had a mechanical fall that resulted in abrasions and a hematoma to his left forehead. The patient presented with dysphagia and anterior neck swelling that progressed rapidly into airway compromise requiring endotracheal intubation. Emergent computed tomography revealed a large retropharyngeal hematoma, with active arterial extravasation that was thought to be arising from the thyrocervical trunk on the left. The hematoma measured approximately 6.7 cm transversely and 3.2 cm anteroposteriorly and extended from the level of the lower nasopharynx, down the neck into the retropharyngeal and danger space and into the mediastinum posterior to the esophagus, overall approximately 25 cm. The larynx was deviated anteriorly and there was esophageal compression. An emergent arteriogram and catheterization confirmed bleeding from branches of the ITA, and successful embolization was performed. It is important to recognize the ITA rupture as a potential etiology of an acute airway compromise. In emergent situations, while securing an airway is a priority, rapidly initiating diagnostic testing to confirm the diagnosis and arranging for arterial embolization can be life-saving. PMID- 26819786 TI - Necrotizing ANCA-Positive Glomerulonephritis Secondary to Culture-Negative Endocarditis. AB - Infective endocarditis (IE) and small-vessel vasculitis may have similar clinical features, including glomerulonephritis. Furthermore the association between IE and ANCA positivity is well documented, making differential diagnosis between IE- and ANCA-associated vasculitis particularly difficult, especially in case of culture-negative IE. We report on one patient with glomerulonephritis secondary to culture-negative IE caused by Bartonella henselae which illustrates this diagnostic difficulty. PMID- 26819787 TI - Placenta Accreta in a Woman with Escherichia coli Chorioamnionitis with Intact Membranes. AB - Background. Escherichia coli (E. coli) associated intrauterine infections with intact membranes are extremely rare. Case. A 30-year-old multiparous female presented at 26 weeks' gestation with clinical signs of chorioamnionitis but physical examination suggested intact membranes. Her dietary history was concerned with Listeriosis. An amniocentesis was performed. Shortly thereafter, the mother developed septic shock and an urgent Cesarean delivery was performed. The patient required a peripartum hysterectomy for placenta accreta. Amniotic fluid cultures grew E. coli. PMID- 26819788 TI - Ectopic Pregnancy in Uncommon Implantation Sites: Intramural Pregnancy and Rudimentary Horn Pregnancy. AB - Ectopic pregnancy is commonly located in the fallopian tube. Nevertheless, two unusual types of ectopic pregnancy, intramural pregnancy and rudimentary horn pregnancy, seriously threaten maternal life. The diagnosis and treatment of these unusual implantation sites present a clinical challenge. In this study, we illustrated the two unusual types of ectopic pregnancy and summarized the current data regarding diagnosis and optimal treatment from our experience. PMID- 26819789 TI - Fetal Bowel Dilatation: A Sonographic Sign of Uncertain Prognosis. AB - Fetal bowel dilatation is an indirect sonographic sign of mechanical or functional bowel obstruction. The etiology of fetal bowel dilatation is a difficult prenatal diagnosis since ultrasound has limited accuracy for bowel evaluation. The authors describe a case of fetal bowel dilatation diagnosed in the third trimester. PMID- 26819790 TI - Primary Congenital Glaucoma with Delayed Suprachoroidal Hemorrhage following Combined Trabeculotomy Trabeculectomy and 5-Fluorouracil. AB - Background. Delayed postoperative suprachoroidal hemorrhage (DSCH) may occur following intraocular surgery for the treatment of glaucoma. It is considered to be a rare and debilitating event if not managed appropriately. Reported herewith is a case of Primary Congenital Glaucoma followed by DSCH with successful immediate surgical intervention and visual restoration. Patient and Method. An 8 month-old male child had bilateral Primary Congenital Glaucoma (PCG). Combined Trabeculotomy Trabeculectomy with 5-Fluorouracil (5FU) was performed. He developed delayed suprachoroidal hemorrhage (DSCH) within 24 hours after intraocular surgery which was drained. In addition, he developed exposure keratopathy and left amblyopia. Outcome. Resolution of the DSCH was seen with surgical drainage in addition to treatments for exposure keratopathy and amblyopia. These resulted in reduced intraocular pressure and improved visual acuities. Conclusion. There appears to be a difference in the overall management of PCG and DSCH between adults and children. A high index of suspicion as well as emergency surgical treatment for DSCH and associated conditions should be performed on pediatric patients that present with these challenges. PMID- 26819791 TI - Atraumatic Anterior Dislocation of the Hip Joint. AB - Dislocation of the hip joint in adults is usually caused by high-energy trauma such as road traffic accidents or falls from heights. Posterior dislocation is observed in most cases. However, atraumatic anterior dislocation of the hip joint is extremely rare. We present a case of atraumatic anterior dislocation of the hip joint that was induced by an activity of daily living. The possible causes of this dislocation were anterior capsule insufficiency due to developmental dysplasia of the hip, posterior pelvic tilt following thoracolumbar kyphosis due to vertebral fracture, and acetabular anterior coverage changes by postural factor. Acetabular anterior coverage changes in the sagittal plane were measured using a tomosynthesis imaging system. This system was useful for elucidation of the dislocation mechanism in the present case. PMID- 26819792 TI - An Unusual Presentation of Adenoid Cystic Carcinoma. AB - Adenoid cystic carcinoma (ACC) is a relatively rare tumor of epithelial cell origin, most commonly arising from major salivary glands. It is uncommonly found outside the major or minor salivary glands and is especially rare when located in the nasal cavity. Diagnosis and treatment of ACC pose numerous challenges, partly due to its biological behavior of slow growth, high tendency of local recurrence, and perineural invasion. We present the case of a 67-year-old male with complaints of facial pain and swelling, with a CT scan showing a soft tissue mass extending from the right nasal cavity with osseous destruction. Biopsy revealed ACC with perineural invasion. ACC of the nasal cavity continues to pose diagnostic and therapeutic challenges to physicians. Because this rare pathology presents in a vague manner, early diagnosis requires a high index of suspicion for this disease and close follow-up care. Since ACC of the nasal cavity is seldom reported in the literature, it is our hope that reporting these rare instances as case reports will heighten physician awareness of this rare disease, allowing for early diagnosis and treatment. PMID- 26819793 TI - Isolated Ocular Manifestation of Relapsed Chronic Myelogenous Leukemia Presenting as Myeloid Blast Crisis in a Patient on Imatinib Therapy: A Case Report and Review of the Literature. AB - Blast phase in chronic myelogenous leukemia (CML) has rarely been reported to involve extramedullary sites like skin, lymph nodes, and central nervous system. Clinical history, characteristic hematologic findings (elevated leukocyte counts, myelocytic predominance, and basophilia), and Philadelphia chromosome are of high diagnostic significance especially in isolated extramedullary presentations. We describe a unique case of CML relapse with blast phase involving the eye. A 66 year-old man with a known diagnosis of CML on imatinib and in molecular remission for 3 years presented with a painful blind eye. Histologic examination revealed diffuse involvement of choroid, iris, vitreous humor, and the optic nerve by blast cells. The blasts expressed CD34, aberrant TdT, and a myeloid phenotype (CD13, CD33, and CD117). Fluorescence in situ hybridization (FISH) of vitreous fluid detected BCR-ABL1 gene rearrangement. Additionally, trisomy 8 and gains of 9 and 22 were seen which were not present in the initial diagnostic marrow study 3 years ago. At relapse, the bone marrow, peripheral blood, and the cerebrospinal fluid were not involved by CML. Patient received induction chemotherapy and single dose prophylactic intrathecal methotrexate and was maintained on antityrosine kinase therapy and eventually underwent allogenic stem cell transplantation. PMID- 26819794 TI - Invasive Community-Acquired Methicillin-Resistant Staphylococcus aureus in a Japanese Girl with Disseminating Multiple Organ Infection: A Case Report and Review of Japanese Pediatric Cases. AB - Pediatric invasive community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection is very serious and occasionally fatal. This infectious disease is still a relatively rare and unfamiliar infectious disease in Japan. We report a positive outcome in a 23-month-old Japanese girl with meningitis, osteomyelitis, fasciitis, necrotizing pneumonia, urinary tract infection, and bacteremia due to CA-MRSA treated with linezolid. PCR testing of the CA-MRSA strain was positive for PVL and staphylococcal enterotoxin b and negative for ACME. SCC mec was type IVa. This case underscores the selection of effective combinations of antimicrobial agents for its treatment. We need to be aware of invasive CA-MRSA infection, which rapidly progresses with a serious clinical course, because the incidence of the disease may be increasing in Japan. PMID- 26819795 TI - Endobronchial Enigma: A Clinically Rare Presentation of Nocardia beijingensis in an Immunocompetent Patient. AB - Nocardiosis is an opportunistic infection caused by the Gram-positive weakly acid fast, filamentous aerobic Actinomycetes. The lungs are the primary site of infection mainly affecting immunocompromised patients. In rare circumstances even immunocompetent hosts may also develop infection. Diagnosis of pulmonary nocardiosis is usually delayed due to nonspecific clinical and radiological presentations which mimic fungal, tuberculous, or neoplastic processes. The present report describes a rare bronchoscopic presentation of an endobronchial nocardial mass in a 55-year-old immunocompetent woman without underlying lung disease. The patient exhibited signs and symptoms of unresolving community acquired pneumonia with a computed tomography (CT) scan that showed a space occupying lesion and enlarged paratracheal lymph node. This patient represents the unusual presentation of pulmonary Nocardia beijingensis as an endobronchial mass. Pathology obtained during bronchoscopy demonstrated polymerase chain reaction (PCR) confirmation of nocardiosis. Symptoms and clinical findings improved with antibiotic treatment. This patient emphasizes the challenge in making the diagnosis of pulmonary nocardiosis, especially in a low risk host. A literature review presents the difficulties and pitfalls in the clinical assessment of such an individual. PMID- 26819796 TI - Hemorrhagic Pseudocyst of Pancreas Treated with Coil Embolization of Gastroduodenal Artery: A Case Report and Review of Literature. AB - Hemorrhage into pseudocyst of pancreas can rarely present as life threatening massive UGI bleeding. We present a case of 21-year-old male, admitted to our department, who was a known case of posttraumatic acute pancreatitis and who developed massive upper GI bleeding. CT angiography of abdomen showed aneurysm of gastroduodenal artery. Patient was successfully treated with coil embolization of gastroduodenal artery. PMID- 26819797 TI - Isolated Celiac and Splenic Artery Dissection: A Case Report and Review of the Literature. AB - An isolated dissection of the celiac artery is an extremely rare condition that requires a high level of suspicion to evoke the diagnosis. Once established, the natural course is unpredictable in view of the discrepancies in its management requiring a case-by-case analysis. In this paper, we report an unusual case of spontaneous abdominal pain that was diagnosed with celiac and splenic artery rupture secondary to physical stress. This paper underlines the necessity to maintain a high level of suspicion for arterial dissections and we also review the management plan in such cases. PMID- 26819798 TI - Clinical and Epidemiological Factors Associated with Mortality in Parkinson's Disease in a Brazilian Cohort. AB - Background. Prognosis of PD is variable. Most studies show higher mortality rates in PD patients compared to the general population. Clinical and epidemiologic factors predicting mortality are poorly understood. Methods. Clinical and epidemiologic features including patient history and physical, functional, and cognitive scores were collected from a hospital-based cohort of PD patients using standardized protocols and clinical scales. Data on comorbidities and mortality were collected on follow-up. Results. During a mean follow-up of 4.71 years (range 1-10), 43 (20.9%) of the 206 patients died. Those who died had higher mean age at disease onset than those still alive at the last follow-up (67.7 years versus 56.3 years; p < 0.01). In the univariate analysis, age at baseline was associated with decreased survival. In the adjusted Cox proportional hazards model, age at disease onset and race/ethnicity were predictors of mortality. Conclusions. Late age at disease onset and advanced chronological age are associated with decreased survival. Comorbidities and PD characteristics were not associated with decreased survival in our sample. Race/ethnicity was found in our study to be associated with increased hazard of mortality. Our findings indicate the importance of studying survival among different populations of PD patients. PMID- 26819800 TI - Optimization of Gentisides Extraction from Gentiana rigescens Franch. ex Hemsl. by Response Surface Methodology. AB - Gentisides are a class of chemical compounds which is considered as potential therapeutic substance for treatment of neurodegenerative disorders. The heat reflux extraction conditions were optimized for seven kinds of gentisides from the root and rhizome of Gentiana rigescens Franch. ex Hemsl. by employing response surface method. Based on univariate test, a Box-Behnken design (BBD) was applied to the survey of relationships between response value (gentisides yield) and independent variables which were chosen from various extraction processes, including extraction temperature, extraction time, and solvent-material ratio. The optimized conditions for this extraction are as follows: extraction time of 3.40 h, extraction temperature of 74.33 degrees C, and ratio of solvent to raw material of 10.21 : 1 mL/g. Verification assay revealed that the predicted value (99.24%) of extraction parameters from this model was mainly conformed to the experimentally observed values (98.61 +/- 0.61). PMID- 26819799 TI - Epidemiological Observations on Cryptosporidiosis in Diarrheic Goat Kids in Greece. AB - This study aimed at investigating the occurrence of Cryptosporidium spp. in diarrheic goat kids in Greece and the risk factors associated with cryptosporidiosis. Altogether, 292 diarrheic 4-15-day-old goat kids from 54 dairy goat herds of Northern Greece were examined. Oocysts of Cryptosporidium spp. were detected in 223 of 292 (76.4%) goat kids and the intensity of infection was scored as "high" in 142 samples, "moderate" in 45 samples, and "low" in 36 samples. Larger herds (>200 animals) had higher infection rates than smaller ones, although this difference was not statistically significant. Significantly higher infection rates were observed in herds during late kidding season (1 January to 30 April) compared to the early one (1 September to 31 December). These results suggest that cryptosporidiosis is very common in diarrheic goat kids in Greece, especially in large herds during the late parturition season. PMID- 26819801 TI - Association between Chemotherapy-Response Assays and Subsets of Tumor Infiltrating Lymphocytes in Gastric Cancer: A Pilot Study. AB - PURPOSE: The purpose of this pilot study was to evaluate the association between adenosine triphosphate-based chemotherapy response assays (ATP-CRAs) and subsets of tumor infiltrating lymphocytes (TILs) in gastric cancer. MATERIALS AND METHODS: In total, 15 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2011. Chemotherapy response assays were performed on tumor cells from these samples using 11 chemotherapeutic agents, including etoposide, doxorubicin, epirubicin, mitomycin, 5-fluorouracil (5-FU), oxaliplatin, irinotecan, docetaxel, paclitaxel, methotrexate, and cisplatin. TILs in the tissue samples were evaluated using antibodies specific for CD3, CD4, CD8, Foxp3, and Granzyme B. RESULTS: The highest cancer cell death rates were induced by etoposide (44.8%), 5-FU (43.1%), and mitomycin (39.9%). Samples from 10 patients who were treated with 5-FU were divided into 5-FU-sensitive and -insensitive groups according to median cell death rate. No difference was observed in survival between the two groups (P=0.216). Only two patients were treated with a chemotherapeutic agent determined by an ATP-CRA and there was no significant difference in overall survival compared with that of patients treated with their physician's choice of chemotherapeutic agent (P=0.105). However, a high number of CD3 TILs was a favorable prognostic factor (P=0.008). Pearson's correlation analyses showed no association between cancer cell death rates in response to chemotherapeutic agents and subsets of TILs. CONCLUSIONS: Cancer cell death rates in response to specific chemotherapeutic agents were not significantly associated with the distribution of TIL subsets. PMID- 26819802 TI - Oncologic Safety of Laparoscopic Wedge Resection with Gastrotomy for Gastric Gastrointestinal Stromal Tumor: Comparison with Conventional Laparoscopic Wedge Resection. AB - PURPOSE: Various laparoscopic wedge resection (LWR) techniques requiring gastrotomy for gastrointestinal stromal tumors (GISTs) of the stomach have been applied to facilitate tumor resection and preserve the remnant gastric volume. However, there is the possibility of cancer cell dissemination during these procedures. The aim of this study was to assess the oncologic safety of LWR with gastrotomy (LWR-G) compared to LWR without luminal exposure. MATERIALS AND METHODS: Clinicopathologic and operative results of 193 patients who underwent LWR for gastric GIST were retrospectively analyzed from 2003 to 2013. We stratified the patients into two groups: LWR-G and LWR without gastrotomy (LWR C). Clinicopathologic features, short-term outcomes, and long-term outcomes were compared. RESULTS: A total of 26 patients underwent LWR-G, and 167 patients underwent LWR-C. The LWR-G group showed significantly more anterior wall-located (n=10, 38.5%), intraluminal (n=20, 76.9%), and ulcerative (n=13, 50.0%) tumors than the LWR-C group (n=33, 19.8%; n=96, 57.5%; n=46, 27.5%, respectively). Postoperative short-term outcomes did not differ between the two groups. When tumor staging was compared, no statistical difference was noted. There was no recurrence in the LWR-G group, while 2 patients in the LWR-C group experienced recurrence. The two recurrences in the LWR-C group were found in the liver and in the remnant stomach at 63 and 12 months after the operation, respectively. No gastric GIST-related death was recorded in any group during the study period. CONCLUSIONS: LWR-G for gastric GIST is an oncologically safe procedure even for masses with ulcerations. PMID- 26819803 TI - Time-Dependent Effects of Prognostic Factors in Advanced Gastric Cancer Patients. AB - PURPOSE: This study aimed to identify time-dependent prognostic factors and demonstrate the time-dependent effects of important prognostic factors in patients with advanced gastric cancer (AGC). MATERIALS AND METHODS: We retrospectively evaluated 3,653 patients with AGC who underwent curative standard gastrectomy between 1991 and 2005 at the Korea Cancer Center Hospital. Multivariate survival analysis with Cox proportional hazards regression was used in the analysis. A non-proportionality test based on the Schoenfeld residuals (also known as partial residuals) was performed, and scaled Schoenfeld residuals were plotted over time for each covariate. RESULTS: The multivariate analysis revealed that sex, depth of invasion, metastatic lymph node (LN) ratio, tumor size, and chemotherapy were time-dependent covariates violating the proportional hazards assumption. The prognostic effects (i.e., log of hazard ratio [LHR]) of the time-dependent covariates changed over time during follow-up, and the effects generally diminished with low slope (e.g., depth of invasion and tumor size), with gentle slope (e.g., metastatic LN ratio), or with steep slope (e.g., chemotherapy). Meanwhile, the LHR functions of some covariates (e.g., sex) crossed the zero reference line from positive (i.e., bad prognosis) to negative (i.e., good prognosis). CONCLUSIONS: The time-dependent effects of the prognostic factors of AGC are clearly demonstrated in this study. We can suggest that time dependent effects are not an uncommon phenomenon among prognostic factors of AGC. PMID- 26819804 TI - Helicobacter pylori Eradication Reduces the Metachronous Recurrence of Gastric Neoplasms by Attenuating the Precancerous Process. AB - PURPOSE: The importance of Helicobacter pylori eradication after endoscopic resection (ER) of gastric neoplasms remains controversial. In this study, we clarified the importance of H. pylori eradication for metachronous lesions after ER. MATERIALS AND METHODS: This study included 3,882 patients with gastric neoplasms who underwent ER. We included patients infected with H. pylori who received eradication therapy. Among them, 34 patients with metachronous lesions after ER and 102 age- and sex-matched patients (nonmetachronous group) were enrolled. Background mucosal pathologies such as atrophy and intestinal metaplasia (IM) were evaluated endoscopically. The expression levels of CDX1, CDX2, Sonic hedgehog (SHH), and SOX2 were evaluated based on H. pylori eradication and the development of metachronous lesions. RESULTS: The eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.036). Open-type atrophy (P=0.003) and moderate-to-severe IM (P=0.001) occurred more frequently in the metachronous group. In patients with an initial diagnosis of dysplasia, the eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.002). In addition, open type atrophy was more frequent in the metachronous group (P=0.047). In patients with an initial diagnosis of carcinoma, moderate-to-severe IM occurred more frequently in the metachronous group (P=0.003); however, the eradication failure rate was not significantly different between the two groups. SHH and SOX2 expression was increased, and CDX2 expression was decreased in the nonmetachronous group after eradication (P<0.05). CONCLUSIONS: Open-type atrophy, moderate-to-severe IM, and H. pylori eradication failure were significantly associated with metachronous lesions. However, eradication failure was significantly associated with dysplasia, but not carcinoma, in the metachronous group. Thus, H. pylori eradication may play an important role in preventing metachronous lesions after ER for precancerous lesions before carcinomatous transformation. PMID- 26819805 TI - Effect of Carrot Intake in the Prevention of Gastric Cancer: A Meta-Analysis. AB - PURPOSE: Gastric cancer is the third leading cause of cancer-related mortality, with the incidence and mortality being higher in men than in women. Various studies have shown that eating carrots may play a major role in the prevention of gastric cancer. We conducted a meta-analysis to determine the relationship between carrot consumption and gastric cancer. MATERIALS AND METHODS: We searched multiple databases including PubMed, Cochrane Library, Scopus, ScienceDirect, and Persian databases like Scientific Information Database (SID) and IranMedx. The following search terms were used: stomach or gastric, neoplasm or cancer, carcinoma or tumor, and carrot. Statistical analyses were performed using Comprehensive Meta Analysis/2.0 software. RESULTS: We retrieved 81 articles by searching the databases. After considering the inclusion and exclusion criteria, 5 articles were included in this study. The odds ratio (OR) obtained by fixed effects model showed that a 26% reduction in the risk of gastric cancer has been associated with the consumption of carrots) OR=0.74; 95% confidence interval=0.68~0.81; P<0.0001). According to funnel graph, the results showed that the possibility of a publication bias does not exist in this study. CONCLUSIONS: The findings of this study showed an inverse relationship between the consumption of carrots and the risk of gastric cancer. PMID- 26819806 TI - Beginner Surgeon's Initial Experience with Distal Subtotal Gastrectomy for Gastric Cancer Using a Minimally Invasive Approach. AB - PURPOSE: Minimally invasive gastrectomy (MIG), including laparoscopic distal subtotal gastrectomy (LDG) and robotic distal subtotal gastrectomy (RDG), is performed for gastric cancer, and requires a learning period. However, there are few reports regarding MIG by a beginner surgeon trained in MIG for gastric cancer during surgical residency and fellowship. The aim of this study was to report our initial experience with MIG, LDG, and RDG by a trained beginner surgeon. MATERIALS AND METHODS: Between January 2014 and February 2015, a total of 36 patients (20 LDGs and 16 RDGs) underwent MIG by a beginner surgeon during the learning period, and 13 underwent open distal subtotal gastrectomy (ODG) by an experienced surgeon in Bundang CHA Medical Center. Demographic characteristics, operative findings, and short-term outcomes were evaluated for the groups. RESULTS: MIG was safely performed without open conversion in all patients and there was no mortality in either group. There was no significant difference between the groups in demographic factors except for body mass index. There were significant differences in extent of lymph node dissection (LND) (D2 LND: ODG 8.3% vs. MIG 55.6%, P=0.004) and mean operative time (ODG 178.8 minutes vs. MIG 254.7 minutes, P<0.001). The serial changes in postoperative hemoglobin level (P=0.464) and white blood cell count (P=0.644) did not show significant differences between the groups. There were no significant differences in morbidity. CONCLUSIONS: This study showed that the operative and short-term outcomes of MIG for gastric cancer by a trained beginner surgeon were comparable with those of ODG performed by an experienced surgeon. PMID- 26819807 TI - Endoscopic and Laparoscopic Full-Thickness Resection of Endophytic Gastric Submucosal Tumors Very Close to the Esophagogastric Junction. AB - PURPOSE: Gastric submucosal tumors (SMTs) located very close to the esophagogastric junction (EGJ) are a challenge for gastric surgeons. Therefore, this study reports on the experience of using endoscopic and laparoscopic full thickness resection (ELFR) with laparoscopic two-layer suturing in such tumors. MATERIALS AND METHODS: Six patients with gastric SMTs very close to the EGJ underwent ELFR with laparoscopic two-layer suturing at Kyungpook National University Medical Center. With the patient under general anesthesia, the lesser curvature and posterior aspect adjacent to the EGJ were meticulously dissected and visualized using a laparoscopic approach. A partially circumferential full thickness incision at the distal margin of the tumor was then made using an endoscopic approach under laparoscopic guidance. The SMT was resected using laparoscopic ultrasonic shears, and the gastric wall was closed using two-layer suturing. Thereafter, the patency and any leakage were checked through endoscopy. RESULTS: All the ELFR procedures with laparoscopic two-layer suturing were performed successfully without an open conversion. The mean operation time was 139.2+/-30.9 minutes and the blood loss was too minimal to be measured. The tumors from four patients were leiomyomas, while the tumors from the other two patients were gastrointestinal stromal tumors with clear resection margins. All the patients started oral intake on the third postoperative day. There was no morbidity or mortality. The mean hospital stay was 7.7+/-0.8 days. CONCLUSIONS: ELFR with laparoscopic two-layer suturing is a safe treatment option for patients with an SMT close to the EGJ, as major resection of the stomach is avoided. PMID- 26819808 TI - Entirely Laparoscopic Gastrectomy and Colectomy for Remnant Gastric Cancer with Gastric Outlet Obstruction and Transverse Colon Invasion. AB - It is well known that gastrectomy with curative intent is the best way to improve outcomes of patients with remnant gastric cancer. Recently,several investigators reported their experiences with laparoscopic gastrectomy of remnant gastric cancer. We report the case of an 83-year-old female patient who was diagnosed with remnant gastric cancer with obstruction. She underwent an entirely laparoscopic distal gastrectomy with colectomy because of direct invasion of the transverse colon. The operation time was 200 minutes. There were no postoperative complications. The pathologic stage was T4b (transverse colon) N0M0. Our experience suggests that laparoscopic surgerycould be an effective method to improve the surgical outcomes of remnant gastric cancer patients. PMID- 26819809 TI - C-Kit-Negative Gastrointestinal Stromal Tumor in the Stomach. AB - C-kit-negative gastrointestinal stromal tumors (GISTs) are uncommon, and there have been few reports about the diagnosis and treatment of c-kit-negative GISTs in the stomach. We report the case of a patient who was diagnosed with a huge and atypical GIST in the stomach. The GIST was completely resected and finally diagnosed as c-kit-negative GIST based on immunohistochemical staining of tumor cells, which were negative for CD117 and CD34 and positive for Discovered on GIST 1 (DOG1). C-kit-negative GISTs could be treated by complete resection and/or imatinib, which is the same treatment for c-kit-positive GISTs. PMID- 26819810 TI - A Challenging Form of Non-autoimmune Insulin-Dependent Diabetes in a Wolfram Syndrome Patient with a Novel Sequence Variant. AB - Wolfram syndrome type 1 is a rare, autosomal recessive, neurodegenerative disorder that is diagnosed when insulin-dependent diabetes of non-auto-immune origin and optic atrophy are concomitantly present. Wolfram syndrome is also designated by DIDMOAD that stands for its most frequent manifestations: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. With disease progression, patients also commonly develop severe neurological and genito urinary tract abnormalities. When compared to the general type 1 diabetic population, patients with Wolfram Syndrome have been reported to have a form of diabetes that is more easily controlled and with less microvascular complications, such as diabetic retinopathy. We report a case of Wolfram syndrome in a 16-year-old male patient who presented with progressive optic atrophy and severe diabetes with very challenging glycemic control despite intensive therapy since diagnosis at the age of 6. Despite inadequate metabolic control he did not develop any diabetic microvascular complications during the 10-year follow-up period. To further investigate potential causes for this metabolic idiosyncrasy, we performed genetic analyses that revealed a novel combination of homozygous sequence variants that are likely the cause of the syndrome in this family. The identified genotype included a novel sequence variant in the Wolfram syndrome type 1 gene along with a previously described one, which had initially been associated with isolated low frequency sensorineural hearing loss (LFSNHL). Interestingly, our patient did not show any abnormal findings with audiometry testing. PMID- 26819811 TI - Rapid Analysis of Cocaine in Saliva by Surface-Enhanced Raman Spectroscopy. AB - Increases in illicit drug use and the number of emergency-room visits attributable to drug misuse or abuse highlight the need for an efficient, reliable method to detect drugs in patients in order to provide rapid and appropriate care. A surface-enhanced Raman spectroscopy (SERS)-based method was successfully developed to rapidly measure cocaine in saliva at clinical concentrations, as low as 25 ng/mL. Pretreatment steps comprising chemical separation, physical separation, and solid-phase extraction were investigated to recover the analyte drug from the saliva matrix. Samples were analyzed using Fourier-transform (FT) and dispersive Raman systems, and statistical analysis of the results shows that the method is both reliable and accurate, and could be used to quantify unknown samples. The procedure requires minimal space and equipment and can be completed in less than 16 minutes. Finally, due to the inclusion of a buffer solution and the use of multiple robust pretreatment steps, with minimal further development this method could also be applied to other drugs of interest. PMID- 26819813 TI - Retinal safety of near infrared radiation in photovoltaic restoration of sight. AB - Photovoltaic restoration of sight requires intense near-infrared light to effectively stimulate retinal neurons. We assess the retinal safety of such radiation with and without the retinal implant. Retinal damage threshold was determined in pigmented rabbits exposed to 880nm laser radiation. The 50% probability (ED50) of retinal damage during 100s exposures with 1.2mm diameter beam occurred at 175mW, corresponding to a modeled temperature rise of 12.5 degrees C. With the implant, the same temperature was reached at 78mW, close to the experimental ED50 of 71mW. In typical use conditions, the retinal temperature rise is not expected to exceed 0.43 degrees C, well within the safety limits for chronic use. PMID- 26819812 TI - Wavefront sensorless adaptive optics fluorescence biomicroscope for in vivo retinal imaging in mice. AB - Cellular-resolution in vivo fluorescence imaging is a valuable tool for longitudinal studies of retinal function in vision research. Wavefront sensorless adaptive optics (WSAO) is a developing technology that enables high-resolution imaging of the mouse retina. In place of the conventional method of using a Shack Hartmann wavefront sensor to measure the aberrations directly, WSAO uses an image quality metric and a search algorithm to drive the shape of the adaptive element (i.e. deformable mirror). WSAO is a robust approach to AO and it is compatible with a compact, low-cost lens-based system. In this report, we demonstrated a hill-climbing algorithm for WSAO with a variable focus lens and deformable mirror for non-invasive in vivo imaging of EGFP (enhanced green fluorescent protein) labelled ganglion cells and microglia cells in the mouse retina. PMID- 26819814 TI - Retinal nerve fiber layer reflectometry must consider directional reflectance. AB - Recent studies reveal that measurements of retinal nerve fiber layer (RNFL) reflectance provide more sensitive detection of glaucomatous damage than RNFL thickness, but most do not consider directional reflectance of the RNFL, an important source of variability. This study quantitatively compared RNFL directional reflectance, represented by an angular spread function (ASF), measured at different scattering angles, different wavelengths and different distances from the optic nerve head (ONH) and for bundles with different thicknesses (T). An ASF was characterized by its amplitude (A) and width (W). Internal reflectance of a bundle was expressed as A/T. The study found that A varied significantly with scattering angle and wavelength and that A/T was different among bundles but constant along the same bundle, indicating that the internal structure of axons may vary among bundles but does not change with distance. This study also found that W was larger near the ONH and at longer wavelengths, but did not depend on scattering angle or T. Because a 4.3 degrees change in incident angle can change reflected intensity by a factor of 2.7, accounting for directional reflectance should improve the accuracy and reproducibility of RNFL reflectance measurements. PMID- 26819815 TI - STED imaging of green fluorescent nanodiamonds containing nitrogen-vacancy nitrogen centers. AB - We report Stimulated Emission Depletion (STED) imaging of green fluorescent nanodiamonds containing Nitrogen-acancy-Nitrogen (NVN) centers with a resolution of 70 nm using a commercial microscope. Nanodiamonds have been demonstrated to have the potential to be excellent cellular biomarkers thanks to their low toxicity and nonbleaching fluorescence, and are especially appealing for superresolution imaging technique like STED microscopy. However, only red fluorescent nanodiamonds containing Nitrogen-Vacancy (NV) centers have been used with STED microscopy so far. The existence of only one color nonbleaching center limits the possible observations, for instance it complicates spatial correlation studies with STED. To provide a nonbleaching probe in a different color, we characterize here the optical properties of the NVN defect for STED imaging. We demonstrate STED imaging of the green fluorescent nanodiamonds containing NVN centers, opening the door for long term two-color STED observation. Furthermore we exemplify the use of green nanodiamonds as a second color nonbleaching STED biomarker by imaging 70 nm fluorescent crystals up taken into HeLa cells. PMID- 26819816 TI - Surface-modified complex SU-8 microstructures for indirect optical manipulation of single cells. AB - We introduce a method that combines two-photon polymerization (TPP) and surface functionalization to enable the indirect optical manipulation of live cells. TPP made 3D microstructures were coated specifically with a multilayer of the protein streptavidin and non-specifically with IgG antibody using polyethylene glycol diamine as a linker molecule. Protein density on their surfaces was quantified for various coating methods. The streptavidin-coated structures were shown to attach to biotinated cells reproducibly. We performed basic indirect optical micromanipulation tasks with attached structure-cell couples using complex structures and a multi-focus optical trap. The use of such extended manipulators for indirect optical trapping ensures to keep a safe distance between the trapping beams and the sensitive cell and enables their 6 degrees of freedom actuation. PMID- 26819817 TI - Differentiation of cutaneous melanoma from surrounding skin using laser-induced breakdown spectroscopy. AB - Laser-induced breakdown spectroscopy (LIBS) has the potential to be used as a surgical tool for simultaneous tissue ablation and elemental analysis of the ablated tissue. LIBS may be used to distinguish melanoma lesions from the surrounding dermis based on the quantitative difference of elements within melanoma lesions. Here, we measured the elements in homogenized pellets and real tissues from excised skin samples of melanoma-implanted mice. In addition, statistical analysis of LIBS spectra using principal component analysis and linear discriminant analysis was performed. Our results showed that this method had high detection sensitivity, highlighting the potential of this tool in clinical applications. PMID- 26819819 TI - Phase contrast x-ray velocimetry of small animal lungs: optimising imaging rates. AB - Chronic lung diseases affect a vast portion of the world's population. One of the key difficulties in accurately diagnosing and treating chronic lung disease is our inability to measure dynamic motion of the lungs in vivo. Phase contrast x ray imaging (PCXI) allows us to image the lungs in high resolution by exploiting the difference in refractive indices between tissue and air. Combining PCXI with x-ray velocimetry (XV) allows us to track the local motion of the lungs, improving our ability to locate small regions of disease under natural ventilation conditions. Via simulation, we investigate the optimal imaging speed and sequence to capture lung motion in vivo in small animals using XV on both synchrotron and laboratory x-ray sources, balancing the noise inherent in a short exposure with motion blur that results from a long exposure. PMID- 26819818 TI - ATR-FTIR and Raman spectroscopic investigation of the electroporation-mediated transdermal delivery of a nanocarrier system containing an antitumour drug. AB - The aim of the present work was the optimization of the transdermal delivery of a lyotropic liquid crystal genistein-based formulation (LLC-GEN). LLC was chosen as medium in view of the poor solubility of GEN in water. Membrane diffusion and penetration studies were carried out with a Franz diffusion cell, through a synthetic membrane in vitro, a chick chorioallantoic membrane ex ovo, and ex vivo excised human epidermis. Thereafter, LLC-GEN was combined with electroporation (EP) to enhance the transdermal drug delivery. The synergistic effect of EP was verified by in vivo ATR-FTIR and ex vivo Raman spectroscopy on hairless mouse skin. PMID- 26819820 TI - Avian embryo monitoring during incubation using multi-channel diffuse speckle contrast analysis. AB - Determining the survival rate of avian embryos during incubation is essential for cost-saving in the poultry industry. A multi-channel diffuse speckle contrast analysis (DSCA) system, comprising four optical fiber channels, is proposed to achieve noninvasive in vivo measurements of deep tissue flow. The system was able to monitor chick embryo vital signs over the entire incubation period. Moreover, it proved useful in distinguishing between chick embryos in healthy and weakened conditions. PMID- 26819821 TI - Alteration in refractive index profile during accommodation based on mechanical modelling. AB - The lens of the eye has a gradient refractive index (GRIN). Ocular accommodation, which alters the shape of the lens in response to visual demand, causes a redistribution of the internal structure of the lens leading to a change in the GRIN profile. The nature of this redistribution and the consequence of change in the GRIN profile are not understood. A modelling approach that considers how the GRIN profile may change with accommodation needs to take into account optical and mechanical parameters and be cognisant of individual variability in the shape and size of lenses. This study models the normalised axial GRIN profile during accommodation using reduced modelling and incorporating finite element analysis to connect inhomogenous mechanical characteristics of the lens to optical performance. The results show that simulated stretching changes the length of the plateau but does not alter the cortical gradient, which supports clinical findings. There is a very small change to the accommodated and non-accommodated profiles when normalised, yet this yields measurable changes in aberrations with around 11% and almost 13% difference in spherical aberration and astigmatism respectively. The results can be used in reconstruction of the refractive index and for investigating gradual changes with age. PMID- 26819822 TI - Multiplexed fluorescence tomography with spectral and temporal data: demixing with intrinsic regularization. AB - We consider the joint use of spectral and temporal data for multiplexed fluorescence molecular tomography to enable high-throughput imaging of multiple fluorescent targets in bulk tissue. This is a challenging problem due to the narrow near-infrared diagnostic window and relatively broad emission spectra of common fluorophores, and the distortion ("redshift") that the fluorophore signals undergo as they propagate through tissue. We show through a Cramer-Rao lower bound analysis that demixing with spectral-temporal data could result in an order of magnitude improvement in performance over either modality alone. To cope with the resulting large data set, we propose a novel two-stage algorithm that decouples the demixing and tomographic reconstruction operations. In this work we concentrate on the demixing stage. We introduce an approach which incorporates ideas from sparse subspace clustering and compressed sensing and does not require a regularization parameter. We report on simulations in which we simultaneously demixed four fluorophores with closely overlapping spectral and temporal profiles in a 25 mm diameter cross-sectional area with a root-mean-square error of less than 3% per fluorophore, as well as on studies of sensitivity of the method to model mismatch. PMID- 26819823 TI - Doxorubicin loaded nanodiamond-silk spheres for fluorescence tracking and controlled drug release. AB - Nanoparticle (NP) based technologies have proved to be considerably beneficial for advances in biomedicine especially in the areas of disease detection, drug delivery and bioimaging. Over the last few decades, NPs have garnered interest for their exemplary impacts on the detection, treatment, and prevention of cancer. The full potential of these technologies are yet to be employed for clinical use. The ongoing research and development in this field demands single multifunctional composite materials that can be employed simultaneously for drug delivery and biomedical imaging. In this manuscript, a unique combination of silk fibroin (SF) and nanodiamonds (NDs) in the form of nanospheres are fabricated and investigated. The spheres were loaded with the anthracyline Doxorubicin (DoX) and the drug release kinetics for these ND-SF-DoX (NDSX) spheres were studied. NDs provided the fluorescence modality for imaging while the degradable SF spheres stabilized and released the drug in a controlled manner. The emission and structural properties of the spheres were characterized during drug release. The degradability of SF and the subsequent release of DoX from the spheres were monitored through fluorescence of NDs inside the spheres. This research demonstrates the enormous potential of the ND-SF nanocomposite platforms for diagnostic and therapeutic purposes, which are both important for pharmaceutical research and clinical settings. PMID- 26819824 TI - Label-free multi-photon imaging of dysplasia in Barrett's esophagus. AB - Barrett's esophagus (BE) is a metaplastic disorder where dysplastic and early cancerous changes are invisible to the naked eye and where the practice of blind biopsy is hampered by large sampling errors. Multi-photon microscopy (MPM) has emerged as an alternative solution for fast and label-free diagnostic capability for identifying the histological features with sub-micron accuracy. We developed a compact, inexpensive MPM system by using a handheld mode-locked fiber laser operating at 1560nm to study mucosal biopsies of BE. The combination of back scattered THG, back-reflected forward THG and SHG signals generate images of cell nuclei and collagen, leading to label-free diagnosis in Barrett's. PMID- 26819825 TI - Deep-UV biological imaging by lanthanide ion molecular protection. AB - Deep-UV (DUV) light is a sensitive probe for biological molecules such as nucleobases and aromatic amino acids due to specific absorption. However, the use of DUV light for imaging is limited because DUV can destroy or denature target molecules in a sample. Here we show that trivalent ions in the lanthanide group can suppress molecular photodegradation under DUV exposure, enabling a high signal-to-noise ratio and repetitive DUV imaging of nucleobases in cells. Underlying mechanisms of the photodegradation suppression can be excitation relaxation of the DUV-absorptive molecules due to energy transfer to the lanthanide ions, and/or avoiding ionization and reactions with surrounding molecules, including generation of reactive oxygen species, which can modify molecules that are otherwise transparent to DUV light. This approach, directly removing excited energy at the fundamental origin of cellular photodegradation, indicates an important first step towards the practical use of DUV imaging in a variety of biological applications. PMID- 26819826 TI - Generalized mesh-based Monte Carlo for wide-field illumination and detection via mesh retessellation. AB - Monte Carlo methods are commonly used as the gold standard in modeling photon transport through turbid media. With the rapid development of structured light applications, an accurate and efficient method capable of simulating arbitrary illumination patterns and complex detection schemes over large surface area is in great need. Here we report a generalized mesh-based Monte Carlo algorithm to support a variety of wide-field illumination methods, including spatial-frequency domain imaging (SFDI) patterns and arbitrary 2-D patterns. The extended algorithm can also model wide-field detectors such as a free-space CCD camera. The significantly enhanced flexibility of source and detector modeling is achieved via a fast mesh retessellation process that combines the target domain and the source/detector space in a single tetrahedral mesh. Both simulations of complex domains and comparisons with phantom measurements are included to demonstrate the flexibility, efficiency and accuracy of the extended algorithm. Our updated open source software is provided at http://mcx.space/mmc. PMID- 26819827 TI - In vivo photothermal treatment by the peritumoral injection of macrophages loaded with gold nanoshells. AB - Photothermal treatment methods have been widely studied for their target specificity and potential for supplementing the limitations of conventional surgical treatments. In this study, we conducted in vivo photothermal treatments using macrophages containing nanoshells as live vectors. We injected macrophages at the peritumoral sites and observed that they had penetrated into the tumor approximately 48 hours after injection. Afterwards, we irradiated with a near infrared laser for 2 minutes at 1 W/cm(2), causing cancer cell death. Our study identified the optimal conditions of the photothermal treatment and confirmed the feasibility of its use in in vivo treatments. PMID- 26819828 TI - Compact plane illumination plugin device to enable light sheet fluorescence imaging of multi-cellular organisms on an inverted wide-field microscope. AB - We developed a compact plane illumination plugin (PIP) device which enabled plane illumination and light sheet fluorescence imaging on a conventional inverted microscope. The PIP device allowed the integration of microscope with tunable laser sheet profile, fast image acquisition, and 3-D scanning. The device is both compact, measuring approximately 15 by 5 by 5 cm, and cost-effective, since we employed consumer electronics and an inexpensive device molding method. We demonstrated that PIP provided significant contrast and resolution enhancement to conventional microscopy through imaging different multi-cellular fluorescent structures, including 3-D branched cells in vitro and live zebrafish embryos. Imaging with the integration of PIP greatly reduced out-of-focus contamination and generated sharper contrast in acquired 2-D plane images when compared with the stand-alone inverted microscope. As a result, the dynamic fluid domain of the beating zebrafish heart was clearly segmented and the functional monitoring of the heart was achieved. Furthermore, the enhanced axial resolution established by thin plane illumination of PIP enabled the 3-D reconstruction of the branched cellular structures, which leads to the improvement on the functionality of the wide field microscopy. PMID- 26819829 TI - Farewell editorial from the founding editors. AB - The retiring Editor-in-Chief and Deputy Editor provide a brief retrospective of the first six volumes of Biomedical Optics Express, thank the Editorial Board and OSA professional staff, and endorse the new journal leadership and the continued support of the journal by the biomedical optics community. PMID- 26819830 TI - Time-resolved singlet-oxygen luminescence detection with an efficient and practical semiconductor single-photon detector. AB - In clinical applications, such as PhotoDynamic Therapy, direct singlet-oxygen detection through its luminescence in the near-infrared range (1270 nm) has been a challenging task due to its low emission probability and the lack of suitable single-photon detectors. Here, we propose a practical setup based on a negative feedback avalanche diode detector that is a viable alternative to the current state-of-the art for different clinical scenarios, especially where geometric collection efficiency is limited (e.g. fiber-based systems, confocal microscopy, scanning systems etc.). The proposed setup is characterized with Rose Bengal as a standard photosensitizer and it is used to measure the singlet-oxygen quantum yield of a new set of photosensitizers for site-selective photodynamic therapy. PMID- 26819831 TI - In vivo burn diagnosis by camera-phone diffuse reflectance laser speckle detection. AB - Burn diagnosis using laser speckle light typically employs widefield illumination of the burn region to produce two-dimensional speckle patterns from light backscattered from the entire irradiated tissue volume. Analysis of speckle contrast in these time-integrated patterns can then provide information on burn severity. Here, by contrast, we use point illumination to generate diffuse reflectance laser speckle patterns of the burn. By examining spatiotemporal fluctuations in these time-integrated patterns along the radial direction from the incident point beam, we show the ability to distinguish partial-thickness burns in a porcine model in vivo within the first 24 hours post-burn. Furthermore, our findings suggest that time-integrated diffuse reflectance laser speckle can be useful for monitoring burn healing over time post-burn. Unlike conventional diffuse reflectance laser speckle detection systems that utilize scientific or industrial-grade cameras, our system is designed with a camera phone, demonstrating the potential for burn diagnosis with a simple imager. PMID- 26819832 TI - Correction: Thiol-disulfide Oxidoreductases TRX1 and TMX3 Decrease Neuronal Atrophy in a Lentiviral Mouse Model of Huntington's Disease. AB - [This corrects the article DOI: 10.1371/currents.hd.b966ec2eca8e2d89d2bb4d020be4351e.]. PMID- 26819833 TI - Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance. AB - Insufficient evidence exists to guide the long-term pharmacological management of Huntington's disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such "inverse" associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed. PMID- 26819834 TI - Calcium Handling by Endoplasmic Reticulum and Mitochondria in a Cell Model of Huntington's Disease. AB - Huntington disease (HD) is caused by the CAG (Q) expansion in exon 1 of the IT15 gene encoding a polyglutamine (poly-Q) stretch of the Huntingtin protein (Htt). In the wild type protein, the repeats specify a stretch of up 34 Q in the N terminal portion of Htt. In the pathological protein (mHtt) the poly-Q tract is longer. Proteolytic cleavage of the protein liberates an N-terminal fragment containing the expanded poly-Q tract becomes harmful to cells, in particular to striatal neurons. The fragments cause the transcriptional dysfunction of genes that are essential for neuronal survival. Htt, however, could also have non transcriptional effects, e.g. it could directly alter Ca2+ homeostasis and/or mitochondrial morphology and function. Ca2+ dyshomeostasis and mitochondrial dysfunction are considered important in the molecular aetiology of the disease. Here we have analyzed the effect of the overexpression of Htt fragments (18Q, wild type form, wtHtt and 150Q mutated form, mHtt) on Ca2+ homeostasis in striatal neuronal precursor cells (Q7/7). We have found that the transient overexpression of the Htt fragments increases Ca2+ transients in the mitochondria of cells stimulated with Ca2+-mobilizing agonists. The bulk Ca2+ transients in the cytosol were unaffected, but the Ca2+ content of the endoplasmic reticulum was significantly decreased in the case of mHtt expression. To rule out possible transcriptional effects due to the presence of mHtt, we have measured the mRNA level of a subunit of the respiratory chain complex II, whose expression is commonly altered in many HD models. No effects on the mRNA level was found suggesting that, in our experimental condition, transcriptional action of Htt is not occurring and that the effects on Ca2+ homeostasis were dependent to non transcriptional mechanisms. PMID- 26819835 TI - Clotrimazole as a Cancer Drug: A Short Review. AB - Although clotrimazole was first used against fungal infections, a body of research was later developed indicating that this drug has anticancer properties as well. The mechanism of action is based on the inhibition of mitochondrial bound glycolytic enzymes and calmodulin, which starves cancer cells of energy. Clotrimazole and its derivatives have been shown to decrease rates of cancer cell proliferation, induce G1 phase arrest, and promote pro-apoptotic factors, which lead to cell death. PMID- 26819836 TI - The Impact of Diabetes on Gynecologic Cancer: Current Status and Future Directions. AB - Diabetes mellitus has reached epidemic proportions in both the United States and worldwide with most authorities reporting a doubling in the prevalence of diabetes over the last 20-30 years. While this epidemic is closely tied to obesity, diabetes mellitus presents potential clinical challenges over and above that observed with obesity alone. From a women's health care prospective, this rise in diabetes may impact a woman's health across her lifespan. More specifically, diabetes impacts not only pregnancy as well as well as other medical conditions, but increases the risk for the development of various malignancies. From a gynecologic cancer standpoint, diabetes is most closely associated with endometrial adenocarcinomas, although increasing attention is being placed upon diabetes and ovarian cancer. Attention is also being placed on the potential role of metformin and its impact on outcomes in diabetics with cancer, as well as a potential preventative and/or adjunctive therapy for gynecologic cancer. PMID- 26819837 TI - Unravelling the potential of nitric acid as a surface modifier for improving the hemocompatibility of metallocene polyethylene for blood contacting devices. AB - Design of blood compatible surfaces is obligatory to minimize platelet surface interactions and improve the thromboresistance of foreign surfaces when they are utilized as biomaterials particularly for blood contacting devices. Pure metallocene polyethylene (mPE) and nitric acid (HNO3) treated mPE antithrombogenicity and hydrophilicity were investigated. The contact angle of the mPE treated with HNO3 decreased. Surface of mPE and HNO3 treated mPE investigated with FTIR revealed no major changes in its functional groups. 3D Hirox digital microscopy, SEM and AFM images show increased porosity and surface roughness. Blood coagulation assays prothrombin time (PT) and activated partial thromboplastin time (APTT) were delayed significantly (P < 0.05) for HNO3 treated mPE. Hemolysis assay and platelet adhesion of the treated surface resulted in the lysis of red blood cells and platelet adherence, respectively indicating improved hemocompatibility of HNO3 treated mPE. To determine that HNO3 does not deteriorate elastic modulus of mPE, the elastic modulus of mPE and HNO3 treated mPE was compared and the result shows no significant difference. Hence, the overall observation suggests that the novel HNO3 treated mPE may hold great promises to be exploited for blood contacting devices like grafts, catheters, and etc. PMID- 26819838 TI - The impact of land reform on the status of large carnivores in Zimbabwe. AB - Large carnivores are decreasing in number due to growing pressure from an expanding human population. It is increasingly recognised that state-protected conservation areas are unlikely to be sufficient to protect viable populations of large carnivores, and that private land will be central to conservation efforts. In 2000, a fast-track land reform programme (FTLRP) was initiated in Zimbabwe, ostensibly to redress the racial imbalance in land ownership, but which also had the potential to break up large areas of carnivore habitat on private land. To date, research has focused on the impact of the FTLRP process on the different human communities, while impacts on wildlife have been overlooked. Here we provide the first systematic assessment of the impact of the FTLRP on the status of large carnivores. Spoor counts were conducted across private, resettled and communal land use types in order to estimate the abundance of large carnivores, and to determine how this had been affected by land reform. The density of carnivore spoor differed significantly between land use types, and was lower on resettlement land than on private land, suggesting that the resettlement process has resulted in a substantial decline in carnivore abundance. Habitat loss and high levels of poaching in and around resettlement areas are the most likely causes. The FTLRP resulted in the large-scale conversion of land that was used sustainably and productively for wildlife into unsustainable, unproductive agricultural land uses. We recommended that models of land reform should consider the type of land available, that existing expertise in land management should be retained where possible, and that resettlement programmes should be carefully planned in order to minimise the impacts on wildlife and on people. PMID- 26819839 TI - Potential impact of co-payment at point of care to influence emergency department utilization. AB - Background. Many proponents for healthcare reform suggest increased cost-sharing by patients as a method to reduce overall expenditures. Prior studies on the effects of co-payments for ED visits have generally not been directed toward understanding patient attitudes/behavior at point of care. Objectives. We conducted a survey at point of care to test our hypothesis that a significant number of patients with urgent chief complaints might have avoided the ED if asked to provide a co-payment. Methods. Cross-sectional study design. Stable, oriented, consenting patients at an inner-city, academic ED were consecutively enrolled at hours in which trained research associates were available to assist with data collection. Enrolled patients completed a written survey providing demographic/chief complaint information, and then were asked whether 13 interval amounts of co-payment ranging from 0 to >500 would have impacted their decision to visit the ED. Categorical data are presented as frequency of occurrence and analyzed by chi-square; continuous data presented as means +/- standard deviation, analyzed by t-tests. ORs and 95% confidence intervals provided. Primary outcome parameter was the % of patients who would have avoided the ED if asked to pay any co-payment for several urgent chief complaints: chest pain, SOB, and abdominal pain. Results. A total of 581 patients were enrolled; 63.1% female, mean age 42.4 +/- 15.1 years, 65% Hispanic, 71.2% income less than 20,000, 28.6% less than high school graduate, 81.3% had primary care physician, 57.6% had 2 or more ED visits/past year. Overall, 30.2% of patients chose 0 as the maximum they would have been willing to pay if it was required to be seen in the ED. 16/58 (28%; 95% CI [18-40%]) of chest pain patients, 9/43 (20.9%; 95% CI [11-35%]) of SOB patients, and 24/127 (26.8%; 95% CI [13-27%]) of abdominal pain patients would have been unwilling to pay a co-pay. Patients with income >20,000 were more willing to pay a co-payment (OR = 2.55; 95% CI [1.59-4.10]). No significant relationship was identified between willingness to pay for: gender, race, education, established primary care provider, and frequency of ED visits. Conclusion. Overall, 30.2% of our patients would not have accepted a co-pay in order to be seen, including more than 20% of the patients with chest pain, shortness of breath, and abdominal pain respectively. PMID- 26819840 TI - Trends and topics in eye disease research in PubMed from 2010 to 2014. AB - BACKGROUND: The purpose of this study is to provide a report on scientific production during the period 2010-2014 in order to identify the major topics as well as the predominant actors (journals, countries, continents) involved in the field of eye disease. METHODS: A PubMed search was carried out to extract articles related to eye diseases during the period 2010-2014. Data were downloaded and processed through developed PHP scripts for further analysis. RESULTS: A total of 62,123 articles were retrieved. A total of 3,368 different journals were found, and 19 journals were identified as "core journals" according to Braford's law. English was by far the predominant language. A total of 853,182 MeSH terms were found, representing an average of 13.73 (SD = 4.98) MeSH terms per article. Among these 853,182 MeSH terms, 14,689 different MeSH terms were identified. Vision Disorders, Glaucoma, Diabetic Retinopathy, Macular Degeneration, and Cataract were the most frequent five MeSH terms related to eye diseases. The analysis of the total number of publications showed that Europe and Asia were the most productive continents, and the USA and China the most productive countries. Interestingly, using the mean Five-Year Impact Factor, the two most productive continents were North America and Oceania. After adjustment for population, the overall ranking positions changed in favor of smaller countries (i.e. Iceland, Switzerland, Denmark, and New Zealand), while after adjustment for Gross Domestic Product (GDP), the overall ranking positions changed in favor of some developing countries (Malawi, Guatemala, Singapore). CONCLUSIONS: Due to the large number of articles included and the numerous parameters analyzed, this study provides a wide view of scientific productivity related to eye diseases during the period 2010-2014 and allows us to better understand this field. PMID- 26819841 TI - Pharmacophagy in green lacewings (Neuroptera: Chrysopidae: Chrysopa spp.)? AB - Green lacewings (Neuroptera: Chrysopidae) are voracious predators of aphids and other small, soft-bodied insects and mites. Earlier, we identified (1R,2S,5R,8R) iridodial from wild males of the goldeneyed lacewing, Chrysopa oculata Say, which is released from thousands of microscopic dermal glands on the abdominal sterna. Iridodial-baited traps attract C. oculata and other Chrysopa spp. males into traps, while females come to the vicinity of, but do not usually enter traps. Despite their healthy appearance and normal fertility, laboratory-reared C. oculata males do not produce iridodial. Surprisingly, goldeneyed lacewing males caught alive in iridodial-baited traps attempt to eat the lure and, in Asia, males of other Chrysopa species reportedly eat the native plant, Actinidia polygama (Siebold & Zucc.) Maxim. (Actinidiaceae) to obtain the monoterpenoid, neomatatabiol. These observations suggest that Chrysopa males must sequester exogenous natural iridoids in order to produce iridodial; we investigated this phenomenon in laboratory feeding studies. Lacewing adult males fed various monoterpenes reduced carbonyls to alcohols and saturated double bonds, but did not convert these compounds to iridodial. Only males fed the common aphid sex pheromone component, (1R,4aS,7S,7aR)-nepetalactol, produced (1R,2S,5R,8R) iridodial. Furthermore, although C. oculata males fed the second common aphid sex pheromone component, (4aS,7S,7aR)-nepetalactone, did not produce iridodial, they did convert ~75% of this compound to the corresponding dihydronepetalactone, and wild C. oculata males collected in early spring contained traces of this dihydronepetalactone. These findings are consistent with the hypothesis that Chrysopa males feed on oviparae (the late-season pheromone producing stage of aphids) to obtain nepetalactol as a precursor to iridodial. In the spring, however, wild C. oculata males produce less iridodial than do males collected later in the season. Therefore, we further hypothesize that Asian Chrysopa eat A. polygama to obtain iridoid precursors in order to make their pheromone, and that other iridoid-producing plants elsewhere in the world must be similarly usurped by male Chrysopa species to sequester pheromone precursors. PMID- 26819842 TI - Rat liver regeneration following ablation with irreversible electroporation. AB - During the past decade, irreversible electroporation (IRE) ablation has emerged as a promising tool for the treatment of multiple diseases including hepatic cancer. However, the mechanisms behind the tissue regeneration following IRE ablation have not been investigated. Our results indicate that IRE treatment immediately kills the cells at the treatment site preserving the extracellular architecture, in effect causing in vivo decellularization. Over the course of 4 weeks, progenitor cell differentiation, through YAP and notch pathways, together with hepatocyte expansion led to almost complete regeneration of the ablated liver leading to the formation of hepatocyte like cells at the ablated zone. We did not observe significant scarring or tumor formation at the regenerated areas 6 months post IRE. Our study suggests a new model to study the regeneration of liver when the naive extracellular matrix is decellularized in vivo with completely preserved extracellular architecture. PMID- 26819843 TI - Expression patterns of cysteine peptidase genes across the Tribolium castaneum life cycle provide clues to biological function. AB - The red flour beetle, Tribolium castaneum, is a major agricultural pest responsible for considerable loss of stored grain and cereal products worldwide. T. castaneum larvae have a highly compartmentalized gut, with cysteine peptidases mostly in the acidic anterior part of the midgut that are critical to the early stages of food digestion. In previous studies, we described 26 putative cysteine peptidase genes in T. castaneum (types B, L, O, F, and K) located mostly on chromosomes 3, 7, 8, and 10. In the present study, we hypothesized that specific cysteine peptidase genes could be associated with digestive functions for food processing based on comparison of gene expression profiles in different developmental stages, feeding and non-feeding. RNA-Seq was used to determine the relative expression of cysteine peptidase genes among four major developmental stages (egg, larvae, pupae, and adult) of T. castaneum. We also compared cysteine peptidase genes in T. castaneum to those in other model insects and coleopteran pests. By combining transcriptome expression, phylogenetic comparisons, response to dietary inhibitors, and other existing data, we identified key cysteine peptidases that T. castaneum larvae and adults use for food digestion, and thus new potential targets for biologically-based control products. PMID- 26819844 TI - Arthropods of the great indoors: characterizing diversity inside urban and suburban homes. AB - Although humans and arthropods have been living and evolving together for all of our history, we know very little about the arthropods we share our homes with apart from major pest groups. Here we surveyed, for the first time, the complete arthropod fauna of the indoor biome in 50 houses (located in and around Raleigh, North Carolina, USA). We discovered high diversity, with a conservative estimate range of 32-211 morphospecies, and 24-128 distinct arthropod families per house. The majority of this indoor diversity (73%) was made up of true flies (Diptera), spiders (Araneae), beetles (Coleoptera), and wasps and kin (Hymenoptera, especially ants: Formicidae). Much of the arthropod diversity within houses did not consist of synanthropic species, but instead included arthropods that were filtered from the surrounding landscape. As such, common pest species were found less frequently than benign species. Some of the most frequently found arthropods in houses, such as gall midges (Cecidomyiidae) and book lice (Liposcelididae), are unfamiliar to the general public despite their ubiquity. These findings present a new understanding of the diversity, prevalence, and distribution of the arthropods in our daily lives. Considering their impact as household pests, disease vectors, generators of allergens, and facilitators of the indoor microbiome, advancing our knowledge of the ecology and evolution of arthropods in homes has major economic and human health implications. PMID- 26819845 TI - Revised phylogenetic analysis of the Aetosauria (Archosauria: Pseudosuchia); assessing the effects of incongruent morphological character sets. AB - Aetosauria is an early-diverging clade of pseudosuchians (crocodile-line archosaurs) that had a global distribution and high species diversity as a key component of various Late Triassic terrestrial faunas. It is one of only two Late Triassic clades of large herbivorous archosaurs, and thus served a critical ecological role. Nonetheless, aetosaur phylogenetic relationships are still poorly understood, owing to an overreliance on osteoderm characters, which are often poorly constructed and suspected to be highly homoplastic. A new phylogenetic analysis of the Aetosauria, comprising 27 taxa and 83 characters, includes more than 40 new characters that focus on better sampling the cranial and endoskeletal regions, and represents the most comprenhensive phylogeny of the clade to date. Parsimony analysis recovered three most parsimonious trees; the strict consensus of these trees finds an Aetosauria that is divided into two main clades: Desmatosuchia, which includes the Desmatosuchinae and the Stagonolepidinae, and Aetosaurinae, which includes the Typothoracinae. As defined Desmatosuchinae now contains Neoaetosauroides engaeus and several taxa that were previously referred to the genus Stagonolepis, and a new clade, Desmatosuchini, is erected for taxa more closely related to Desmatosuchus. Overall support for some clades is still weak, and Partitioned Bremer Support (PBS) is applied for the first time to a strictly morphological dataset demonstrating that this weak support is in part because of conflict in the phylogenetic signals of cranial versus postcranial characters. PBS helps identify homoplasy among characters from various body regions, presumably the result of convergent evolution within discrete anatomical modules. It is likely that at least some of this character conflict results from different body regions evolving at different rates, which may have been under different selective pressures. PMID- 26819846 TI - Revisiting the Zingiberales: using multiplexed exon capture to resolve ancient and recent phylogenetic splits in a charismatic plant lineage. AB - The Zingiberales are an iconic order of monocotyledonous plants comprising eight families with distinctive and diverse floral morphologies and representing an important ecological element of tropical and subtropical forests. While the eight families are demonstrated to be monophyletic, phylogenetic relationships among these families remain unresolved. Neither combined morphological and molecular studies nor recent attempts to resolve family relationships using sequence data from whole plastomes has resulted in a well-supported, family-level phylogenetic hypothesis of relationships. Here we approach this challenge by leveraging the complete genome of one member of the order, Musa acuminata, together with transcriptome information from each of the other seven families to design a set of nuclear loci that can be enriched from highly divergent taxa with a single array-based capture of indexed genomic DNA. A total of 494 exons from 418 nuclear genes were captured for 53 ingroup taxa. The entire plastid genome was also captured for the same 53 taxa. Of the total genes captured, 308 nuclear and 68 plastid genes were used for phylogenetic estimation. The concatenated plastid and nuclear dataset supports the position of Musaceae as sister to the remaining seven families. Moreover, the combined dataset recovers known intra- and inter family phylogenetic relationships with generally high bootstrap support. This is a flexible and cost effective method that gives the broader plant biology community a tool for generating phylogenomic scale sequence data in non-model systems at varying evolutionary depths. PMID- 26819847 TI - The association between maternal psychological stress and inflammatory cytokines in allergic young children. AB - Background. Previous studies have shown that psychological stress is linked to asthma prevalence. Parental psychological stress may potentially influence inflammatory responses in their allergic children. The purpose of this study is to clarify the association between maternal psychological status and inflammatory response of allergic young children. Methods. The study subjects were 152 young allergic children (median age: 13 months) who had not shown any allergic symptoms in the past one month. mRNA expression levels of the inflammatory response genes IL-6, IL-8, IL-10 and IL-22 were quantified by qRT-PCR. Maternal psychological status was assessed by standardized questionnaires: the Centre for Epidemiological Studies Depression Scale (CES-D) for depression and the Japanese Perceived Stress Scale (JPSS) for perceived stress. Results. A significant positive association was observed between maternal CES-D scores and IL-6 mRNA expression in the children with asthma. The JPSS scores were also positively associated with IL-8 mRNA expression in asthmatic children and IL-6 mRNA expression in children with allergic rhinitis. Similar trends were observed among children positive for house dust mite-specific IgE, but these associations were not significant. Conclusion. This study supports the hypothesis that maternal psychological stress affects the inflammatory response in their allergic children. PMID- 26819848 TI - The Iflaviruses Sacbrood virus and Deformed wing virus evoke different transcriptional responses in the honeybee which may facilitate their horizontal or vertical transmission. AB - Sacbrood virus (SBV) and Deformed wing virus (DWV) are evolutionarily related positive-strand RNA viruses, members of the Iflavirus group. They both infect the honeybee Apis mellifera but have strikingly different levels of virulence when transmitted orally. Honeybee larvae orally infected with SBV usually accumulate high levels of the virus, which halts larval development and causes insect death. In contrast, oral DWV infection at the larval stage usually causes asymptomatic infection with low levels of the virus, although high doses of ingested DWV could lead to DWV replicating to high levels. We investigated effects of DWV and SBV infection on the transcriptome of honeybee larvae and pupae using global RNA-Seq and real-time PCR analysis. This showed that high levels of SBV replication resulted in down-regulation of the genes involved in cuticle and muscle development, together with changes in expression of putative immune-related genes. In particular, honeybee larvae with high levels of SBV replication, with and without high levels of DWV replication, showed concerted up-regulated expression of antimicrobial peptides (AMPs), and down-regulated expression of the prophenoloxidase activating enzyme (PPAE) together with up-regulation of the expression of a putative serpin, which could lead to the suppression of the melanisation pathway. The effects of high SBV levels on expression of these immune genes were unlikely to be a consequence of SBV-induced developmental changes, because similar effects were observed in honeybee pupae infected by injection. In the orally infected larvae with high levels of DWV replication alone we observed no changes of AMPs or of gene expression in the melanisation pathway. In the injected pupae, high levels of DWV alone did not alter expression of the tested melanisation pathway genes, but resulted in up-regulation of the AMPs, which could be attributed to the effect of DWV on the regulation of AMP expression in response to wounding. We propose that the difference in expression of the honeybee immune genes induced by SBV and DWV may be an evolutionary adaptation to the different predominant transmission routes used by these viruses. PMID- 26819849 TI - The role of geography and host abundance in the distribution of parasitoids of an alien pest. AB - Chalcid wasps (Hymenoptera: Chalcidoidea) are probably the most effective and abundant parasitoids of the horse chestnut leaf miner (Cameraria ohridella), an alien pest in Europe that lacks specialized enemies. We studied how the species richness and abundance of chalcids are influenced by altitude, direction of an alien spread and host abundance of C. ohridella. We quantified the numbers and species richness of chalcid wasps and the numbers of C. ohridella that emerged from horse chestnut (Aesculus hippocastanum) leaf litter samples collected from 35 sites in the Czech Republic. Species richness of chalcids, which was considered an indicator of the possible adaptation of parasitoids to this alien host, was unrelated to C. ohridella abundance, direction of spread, or altitude. Chalcid abundance, which was considered an indicator of parasitism of the alien host, was strongly and positively related to C. ohridella abundance. Chalcid abundance was negatively related to direction of spread and positively related, although in a non-linear manner, to altitude. The relationship of chalcid abundance with direction of spread and altitude was weaker than that with C. ohridella abundance. The results provide evidence that biological control of the alien pest C. ohridella by natural enemies might develop in the future. PMID- 26819850 TI - Comparative morphology of the mouthparts of the megadiverse South African monkey beetles (Scarabaeidae: Hopliini): feeding adaptations and guild structure. AB - Although anthophilous Coleoptera are regarded to be unspecialised flower-visiting insects, monkey beetles (Scarabaeidae: Hopliini) represent one of the most important groups of pollinating insects in South Africa's floristic hotspot of the Greater Cape Region. South African monkey beetles are known to feed on floral tissue; however, some species seem to specialise on pollen and/or nectar. The present study examined the mouthpart morphology and gut content of various hopliine species to draw conclusions on their feeding preferences. According to the specialisations of their mouthparts, the investigated species were classified into different feeding groups. Adaptations to pollen-feeding included a well developed, toothed molar and a lobe-like, setose lacinia mobilis on the mandible as well as curled hairs or sclerotized teeth on the galea of the maxillae. Furthermore, elongated mouthparts were interpreted as adaptations for nectar feeding. Floral- and folial-tissue feeding species showed sclerotized teeth on the maxilla, but the lacinia was mostly found to be reduced to a sclerotized ledge. While species could clearly be identified as floral or folial tissue feeding, several species showed intermediate traits suggesting both pollen and nectar feeding adaptations. Mismatches found between mouthpart morphology and previously reported flower visiting behaviours across different genera and species requires alternative explanations, not necessarily associated with feeding preferences. Although detailed examinations of the mouthparts allowed conclusions about the feeding preference and flower-visiting behaviour, additional morphological and behavioural investigations, combined with greater taxon sampling and phylogenetic data, are still necessary to fully understand hopliine host plant relationships, related to monkey beetle diversity. PMID- 26819851 TI - Association of trait and specific hopes: cross sectional study on students and workers of health professions in Split, Croatia. AB - Introduction. Hope (hoping) is most commonly assessed as a dispositional trait and associated with quality of life, self-care agency and non-attempts of suicide. However, little research has been conducted on hoping for specific events. Materials and Methods. We distributed a survey consisting of Integrative Hope Scale (IHS) and visual analogue scales on which respondents could declare their levels (intensity) of hope for specific events, to all first year health students enrolled at the University Department of Health Studies, Split, Croatia in 2011/2012, as well as to working health professionals attending a nursing conference in April 2012. Results. A total of 161 (89.4%) students and 88 (89.8%) working health professionals returned the completed questionnaires. We found high trait hope scores of students and working health professionals (Md = 111, 95% CI [109-113] vs. Md = 115, 95% CI [112-119]; U = 5,353, P = 0.065), and weak to moderate correlations of trait and specific hopes (r = 0.18-0.48, Spearman's rank correlation coefficient). Students and workers reported 31 different things they hoped for most in life, of which the most prevalent were being healthy and happy. There was very little agreement between participants' reported influence of the four factors compromising the trait hope (self-confidence, ambition, optimism, and social support) on their specific hopes. Conclusions. Our findings, while strengthening the validity of hope as a trait, indicate that specific hopes of individuals are moderated by factors not captured by the IHS trait scale. Further research should explore specific hoping in detail, as well as the effectiveness of interventions aimed at increasing specific or generalized hoping. PMID- 26819852 TI - Molecular diversity of bacteria in commercially available "Spirulina" food supplements. AB - The cyanobacterium Arthrospira is among the most well-known food supplements worldwide known as "Spirulina." While it is a widely recognized health-promoting natural product, there are no reports on the molecular diversity of commercially available brands of "Spirulina" supplements and the occurrence of other cyanobacterial and heterotrophic bacterial microorganisms in these products. In this study, 454-pyrosequencing analysis of the total bacterial occurrence in 31 brands of "Spirulina" dietary supplements from the Greek market was applied for the first time. In all samples, operational taxonomic units (OTUs) of Arthrospira platensis were the predominant cyanobacteria. Some products contained additional cyanobacterial OTUs including a few known potentially toxic taxa. Moreover, 469 OTUs were detected in all 31 products collectively, with most of them being related to the Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria and Verrucomicrobia. All samples included heterotrophic bacterial OTUs, ranging from 9-157 per product. Among the most common OTUs were ones closely related to taxa known for causing health issues (i.e., Pseudomonas, Flavobacterium, Vibrio, Aeromonas, Clostridium, Bacillus, Fusobacterium, Enterococcus). The observed high cyanobacterial and heterotrophic bacterial OTUs richness in the final product is a point for further research on the growth and processing of Arthrospira biomass for commercial purposes. PMID- 26819853 TI - Chronic unpredicted mild stress-induced depression alter saxagliptin pharmacokinetics and CYP450 activity in GK rats. AB - Background. This study was to explore the pharmacokinetics of saxagliptin (Sax) in Goto-Kakizaki (GK) rats complicated with depression induced by chronic unpredicted mild stress (CUMS). The comorbidity of diabetic patients with depression is becoming more and more epidemic. Whether depression mental disorder alters the pharmacokinetics of hypoglycemic drugs in diabetes patients is not clear. Methods. Five-week-old male GK rats were kept in the cage for 7 weeks in a specific pathogen free (SPF)-grade lab until the emergence of diabetes and were then divided into two groups: control group and depression model group. Rats in the CUMS-induced depression group were exposed to a series of stressors for 8 weeks. Plasma serotonin and dopamine levels and behavior of open-field test were used to confirm the establishment of the depression model. All rats were given 0.5 mg/kg Sax orally after 8 weeks and blood samples were collected at different time points. The Sax concentration was assayed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The CYP450 activity of the liver microsomes was determined by using cocktails of probe drugs in which the activities of CYP enzymes were assessed through the determination of the production of the probe drugs. Results. Statistically significant differences in Sax pharmacokinetics were observed for area under curve, clearance, peak concentration, peak time and mean residence time between the depression rats and the control rats, while no statistical differences were observed for half-time and distribution volume by HPLC-MS/MS analysis. The CYP450 activity had different changes in the depression group. Conclusions. These results indicated that CUMS induced depression alters the drug metabolic process of Sax and CYP450 activity of the liver microsomal enzymes in GK rats. PMID- 26819854 TI - The impact of freeze-drying infant fecal samples on measures of their bacterial community profiles and milk-derived oligosaccharide content. AB - Infant fecal samples are commonly studied to investigate the impacts of breastfeeding on the development of the microbiota and subsequent health effects. Comparisons of infants living in different geographic regions and environmental contexts are needed to aid our understanding of evolutionarily-selected milk adaptations. However, the preservation of fecal samples from individuals in remote locales until they can be processed can be a challenge. Freeze-drying (lyophilization) offers a cost-effective way to preserve some biological samples for transport and analysis at a later date. Currently, it is unknown what, if any, biases are introduced into various analyses by the freeze-drying process. Here, we investigated how freeze-drying affected analysis of two relevant and intertwined aspects of infant fecal samples, marker gene amplicon sequencing of the bacterial community and the fecal oligosaccharide profile (undigested human milk oligosaccharides). No differences were discovered between the fecal oligosaccharide profiles of wet and freeze-dried samples. The marker gene sequencing data showed an increase in proportional representation of Bacteriodes and a decrease in detection of bifidobacteria and members of class Bacilli after freeze-drying. This sample treatment bias may possibly be related to the cell morphology of these different taxa (Gram status). However, these effects did not overwhelm the natural variation among individuals, as the community data still strongly grouped by subject and not by freeze-drying status. We also found that compensating for sample concentration during freeze-drying, while not necessary, was also not detrimental. Freeze-drying may therefore be an acceptable method of sample preservation and mass reduction for some studies of microbial ecology and milk glycan analysis. PMID- 26819855 TI - Microscopical and elemental FESEM and Phenom ProX-SEM-EDS analysis of osteocyte- and blood vessel-like microstructures obtained from fossil vertebrates of the Eocene Messel Pit, Germany. AB - The Eocene (?48 Ma) Messel Pit in Germany is a UNESCO World Heritage Site because of its exceptionally preserved fossils, including vertebrates, invertebrates, and plants. Messel fossil vertebrates are typically characterized by their articulated state, and in some cases the skin, hair, feathers, scales and stomach contents are also preserved. Despite the exceptional macroscopic preservation of Messel fossil vertebrates, the microstructural aspect of these fossils has been poorly explored. In particular, soft tissue structures such as hair or feathers have not been chemically analyzed, nor have bone microstructures. I report here the preservation and recovery of osteocyte-like and blood vessel-like microstructures from the bone of Messel Pit specimens, including the turtles Allaeochelys crassesculpta and Neochelys franzeni, the crocodile Diplocynodon darwini, and the pangolin Eomanis krebsi. I used a Field Emission Scanning Electron Microscope (FESEM) and a Phenom ProX desktop scanning electron microscope (LOT-QuantumDesign) equipped with a thermionic CeB6 source and a high sensitivity multi-mode backscatter electron (BSE) for microscopical and elemental characterization of these bone microstructures. Osteocyte-like and blood vessel like microstructures are constituted by a thin layer (?50 nm thickness), external and internal mottled texture with slightly marked striations. Circular to linear marks are common on the external surface of the osteocyte-like microstructures and are interpreted as microbial troughs. Iron (Fe) is the most abundant element found in the osteocyte-like and blood vessel-like microstructures, but not in the bone matrix or collagen fibril-like microstructures. The occurrence of well preserved soft-tissue elements (at least their physical form) establishes a promising background for future studies on preservation of biomolecules (proteins or DNA) in Messel Pit fossils. PMID- 26819856 TI - Microsatellite markers for Senna spectabilis var. excelsa (Caesalpinioideae, Fabaceae). AB - PREMISE OF THE STUDY: Senna spectabilis var. excelsa (Fabaceae) is a South and Central American tree of great ecological importance and one of the most common species in several sites of seasonally dry forests. Our goal was to develop microsatellite markers to assess the genetic diversity and structure of this species. METHODS AND RESULTS: We designed and assessed 53 loci obtained from a microsatellite-enriched library and an intersimple sequence repeat library. Fourteen loci were polymorphic, and they presented a total of 39 alleles in a sample of 61 individuals from six populations. The mean values of observed and expected heterozygosities were 0.355 and 0.479, respectively. Polymorphism information content was 0.390 and the Shannon index was 0.778. CONCLUSIONS: Polymorphism information content and Shannon index indicate that at least nine of the 14 microsatellite loci developed are moderate to highly informative, and potentially useful for population genetic studies in this species. PMID- 26819857 TI - Lineage-specific evolutionary rate in plants: Contributions of a screening for Cereus (Cactaceae). AB - PREMISE OF THE STUDY: Predictable chloroplast DNA (cpDNA) sequences have been listed for the shallowest taxonomic studies in plants. We investigated whether plastid regions that vary between closely allied species could be applied for intraspecific studies and compared the variation of these plastid segments with two nuclear regions. METHODS: We screened 16 plastid and two nuclear intronic regions for species of the genus Cereus (Cactaceae) at three hierarchical levels (species from different clades, species of the same clade, and allopatric populations). RESULTS: Ten plastid regions presented interspecific variation, and six of them showed variation at the intraspecific level. The two nuclear regions showed both inter- and intraspecific variation, and in general they showed higher levels of variability in almost all hierarchical levels than the plastid segments. DISCUSSION: Our data suggest no correspondence between variation of plastid regions at the interspecific and intraspecific level, probably due to lineage-specific variation in cpDNA, which appears to have less effect in nuclear data. Despite the heterogeneity in evolutionary rates of cpDNA, we highlight three plastid segments that may be considered in initial screenings in plant phylogeographic studies. PMID- 26819858 TI - Microsatellites from Fosterella christophii (Bromeliaceae) by de novo transcriptome sequencing on the Pacific Biosciences RS platform. AB - PREMISE OF THE STUDY: Microsatellite markers were developed in Fosterella christophii (Bromeliaceae) to investigate the genetic diversity and population structure within the F. micrantha group, comprising F. christophii, F. micrantha, and F. villosula. METHODS AND RESULTS: Full-length cDNAs were isolated from F. christophii and sequenced on a Pacific Biosciences RS platform. A total of 1590 high-quality consensus isoforms were assembled into 971 unigenes containing 421 perfect microsatellites. Thirty primer sets were designed, of which 13 revealed a high level of polymorphism in three populations of F. christophii, with four to nine alleles per locus. Each of these 13 loci cross-amplified in the closely related species F. micrantha and F. villosula, with one to six and one to 11 alleles per locus, respectively. CONCLUSIONS: The new markers are promising tools to study the population genetics of F. christophii and to discover species boundaries within the F. micrantha group. PMID- 26819859 TI - Isolation of 91 polymorphic microsatellite loci in the western Mediterranean endemic Carex helodes (Cyperaceae). AB - PREMISE OF THE STUDY: Microsatellite primers were developed for Carex helodes (Cyperaceae), a western Mediterranean endemic that is locally distributed in southern Portugal and southwestern Spain and rare in northern Morocco. METHODS AND RESULTS: One hundred nine nuclear microsatellite markers were developed using a shotgun pyrosequencing method, resulting in 91 polymorphic and 18 monomorphic loci when tested using 19 individuals sampled from five populations from Portugal, Spain, and Morocco. Loci averaged 3.23 alleles per locus (SD = 1.15). In a single population (Cortelha population, Portugal), the 34 most polymorphic loci showed a mean observed heterozygosity of 0.357 (SD = 0.292) and mean expected heterozygosity of 0.384 (SD = 0.255). CONCLUSIONS: Next-generation sequencing allowed us to develop a high number of genetic markers with levels of polymorphism adequate to study gene flow among populations. However, when genotyping the individuals within a population, we found low levels of variation. PMID- 26819860 TI - Isolation and characterization of 28 microsatellite loci for a Korean endemic, Lespedeza maritima (Fabaceae). AB - PREMISE OF THE STUDY: We developed microsatellite primers for Lespedeza maritima (Fabaceae), a Korean endemic shrub, and conducted cross-amplifications for closely related species. METHODS AND RESULTS: We produced 28 polymorphic microsatellite markers through reference mapping of 300-bp paired-end reads obtained from Illumina MiSeq data. For 47 individual plants from two populations, the total alleles numbered two to 13, and observed and expected heterozygosities ranged from 0.067 to 0.867 and from 0.064 to 0.848, respectively. Most of these markers were well amplified in closely related species. CONCLUSIONS: In future research, the microsatellite markers described here will help reveal the taxonomic entity of this species. PMID- 26819861 TI - Development and characterization of polymorphic microRNA-based microsatellite markers in Nelumbo nucifera (Nelumbonaceae). AB - PREMISE OF THE STUDY: Polymorphic microRNA (miRNA)-based microsatellite markers were developed to investigate the genetic diversity and population structure of Nelumbo nucifera (Nelumbonaceae). METHODS AND RESULTS: A total of 485 miRNA-based microsatellites were found from the genomic DNA sequences of N. nucifera. After several rounds of screening, 21 primer pairs flanking di-, tri-, or pentanucleotide repeats were identified that revealed high levels of genetic diversity in four populations with two to five alleles per locus. The observed and expected heterozygosity per locus ranged from 0.000 to 1.000 and from 0.000 to 0.803, respectively. CONCLUSIONS: The polymorphic microsatellite markers will be useful for studying the genetic diversity and population structure of N. nucifera. PMID- 26819862 TI - Primers for low-copy nuclear genes in the Melastomataceae. AB - PREMISE OF THE STUDY: Low-copy nuclear gene primers were developed for phylogenetic studies across the Melastomataceae. METHODS AND RESULTS: Total genomic libraries from eight species in the Melastomataceae along with one transcriptome were used for marker identification and primer design. Eight exon primed intron-crossing markers were amplified with success in taxa of nine tribes in the Melastomataceae. The new markers were directly sequenced for eight samples of closely related species of Miconia (Chaenanthera clade) in the tribe Miconieae. The DNA sequences for the eight loci ranged from 660 to 818 aligned base pairs. Compared with four commonly used markers in other studies, the loci developed here had a higher number of variable sites than plastid spacers (7-16 vs. 26-45) and comparable variation to the ribosomal spacers (28-39). CONCLUSIONS: The novel primer pairs should be useful for a broad range of studies of systematics and evolution in the diverse Melastomataceae. PMID- 26819863 TI - The use of laser light to enhance the uptake of foliar-applied substances into citrus (Citrus sinensis) leaves. AB - PREMISE OF THE STUDY: Uptake of foliar-applied substances across the leaf cuticle is central to world food production as well as for physiological investigations into phloem structure and function. Yet, despite the presence of stomata, foliar application as a delivery system can be extremely inefficient due to the low permeability of leaf surfaces to polar compounds. METHODS: Using laser light to generate microscopic perforations in the leaf cuticle, we tested the penetration of several substances into the leaf, their uptake into the phloem, and their subsequent movement through the phloem tissue. Substances varied in their size, charge, and Stokes radius. RESULTS: The phloem-mobile compounds 2-[N-(7-nitrobenz 2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG), lysine, Biocillin, adenosine triphosphate (ATP), trehalose, carboxyfluorescein-SE, and poly(amidomine) (PAMAM) dendrimer G-4 nanoparticles (4.5 nm in size) showed a high degree of mobility and were able to penetrate and be transported in the phloem. DISCUSSION: Our investigation demonstrated the effectiveness of laser light technology in enhancing the penetration of foliar-applied substances into citrus leaves. The technology is also applicable to the study of phloem mobility of substances by providing a less invasive, highly repeatable, and more quantifiable delivery method. The implied superficial lesions to the leaf can be mitigated by applying a waxy coating. PMID- 26819865 TI - SBRT Treatment of Metachronous Small-Cell and Non-Small-Cell Lung Carcinomas in a Patient with Severe COPD. AB - Stereotactic body radiotherapy (SBRT) has not been widely employed in the treatment of limited-stage (LS) small-cell lung cancer (SCLC), although SBRT finds particular utility in patients medically unfit to undergo surgical resection or radiotherapy with conventional fields. The authors present the case of a 61-year-old female smoker with severe chronic obstructive pulmonary disease (COPD), diagnosed incidentally with LS-SCLC. Concurrent chemoradiotherapy was contraindicated by her poor pulmonary function, and she was treated radically with four cycles of cisplatin and etoposide chemotherapy. This was followed by prophylactic cranial irradiation and consolidative SBRT (48 Gy in 4 fractions) to the residual tumour, which achieved a complete clinical response. Fifteen months following the patient's initial diagnosis, a metachronous Stage IA contralateral non-small cell lung cancer (NSCLC) was incidentally diagnosed and was treated with SBRT (48 Gy in 4 fractions). Although studies have established that the incidence of a second lung cancer is higher in patients with previous SCLC, this case is unique in that both primaries were treated with SBRT. PMID- 26819866 TI - A Simplified Supine Technique Expedites the Delivery of Effective Craniospinal Radiation to Medulloblastoma - Comparison with Other Techniques in the Literature. AB - A 28-year-old man presented to the emergency room with a severe headache of one day's duration. A computerized tomography scan showed a hemorrhagic tumor measuring 3.9 x 4.4 cm in the left cerebellar hemisphere. The resection specimen revealed medulloblastoma. He had two episodes of rebleeding and multiple postoperative issues preventing the use of prone craniospinal radiotherapy. We designed a supine technique for this tall man, which was not complicated to set up. The rapid safe implementation of this technique allowed us to avoid further rebleeding and successfully treat the residual tumor. This technique is the described technique in this case report and is compared to other techniques. At 7.5 years after surgery, he is alive without cancer and with only a mild residual deficit. This case is unusual since the majority of patients with the diagnosis of hemorrhagic medulloblastoma died. PMID- 26819867 TI - Long-term Survival in a Patient with Recurrent Pulmonary Metastases from Uterine Leiomyosarcoma. AB - Chemotherapy is the standard of care for disseminated uterine leiomyosarcoma; however, long-term survival is rarely achieved with this aggressive disease. We report a patient with recurrent pulmonary metastatic disease from uterine leiomyosarcoma who is doing well without significant disease nine years after her initial diagnosis. We discuss her clinical course, the treatment modalities she received, and the clinical evidence supporting these. PMID- 26819868 TI - Message from the Editor-in-Chief. PMID- 26819869 TI - Special Issue:Advanced Techniques of MALDI-TOF MS in Ionization, Instrumentation and Applications. PMID- 26819870 TI - Formation of Benzyl Carbanion in Collision-Induced Dissociation of Deprotonated Phenylalanine Homologues. AB - The fragmentation behavior of deprotonated L-phenylalanine (Phe) and its homologues including L-homophenylalanine (HPA) and L-phenylglycine (PG) was investigated using collision-induced dissociation mass spectrometry coupled with a negative ion atmospheric pressure corona discharge ionization (APCDI) technique. The deprotonated molecules [M-H](-) fragmented to lose unique neutral species, e.g., the loss of NH3, CO2, toluene and iminoglycine for [Phe-H](-); styrene and ethenamine/CO2 for [HPA-H](-); and CO2 for [PG-H](-). All of the fragmentations observed are attributable to the formation of intermediates and/or product ions which include benzyl carbanions having resonance-stabilized structures. The carbanions are formed via proton rearrangement through a transition state or via a simple dissociation reaction. These results suggest that the principal factor governing the fragmentation behavior of deprotonated Phe homologues is the stability of the intermediate and/or product ion structures. PMID- 26819871 TI - Sensitive Detection of Aromatic Hydrophobic Compounds in Water and Perfluorooctane Sulfonate in Human Serum by Surface-Assisted Laser Desorption/Ionization Mass Spectrometry (SALDI-MS) with Amine Functionalized Graphene-Coated Cobalt Nanoparticles. AB - In this article, we describe the application of surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) with the use of amine functionalized graphene-coated cobalt nanoparticles (CoC-NH2 nanoparticles) to analyse aromatic hydrophobic compounds that are known environmental contaminants, including polycyclic aromatic hydrocarbons (PAHs) and pentachlorophenol (PCP). Our results demonstrated that SALDI-MS can detect PCP, anthracene, and pyrene in water. In particular, the CoC-NH2 nanoparticles proved to be an efficient means of capturing PCP in water because of the high adsorption capacity of the nanoparticles for PCP, which resulted in a detectability of 100 ppt. Furthermore, the CoC-NH2 nanoparticles also functioned as an adsorbent for solid-phase extraction of perfluorooctane sulfonate (PFOS) from human serum, displaying good performance with a detectability of 10 ppb by SALDI-MS. PMID- 26819872 TI - Peptide Peak Detection for Low Resolution MALDI-TOF Mass Spectrometry. AB - A new peak detection method has been developed for rapid selection of peptide and its fragment ion peaks for protein identification using tandem mass spectrometry. The algorithm applies classification of peak intensities present in the defined mass range to determine the noise level. A threshold is then given to select ion peaks according to the determined noise level in each mass range. This algorithm was initially designed for the peak detection of low resolution peptide mass spectra, such as matrix-assisted laser desorption/ionization Time-of-Flight (MALDI-TOF) mass spectra. But it can also be applied to other type of mass spectra. This method has demonstrated obtaining a good rate of number of real ions to noises for even poorly fragmented peptide spectra. The effect of using peak lists generated from this method produces improved protein scores in database search results. The reliability of the protein identifications is increased by finding more peptide identifications. This software tool is freely available at the Mass++ home page (http://www.first ms3d.jp/english/achievement/software/). PMID- 26819873 TI - Salt Tolerance Enhancement of Liquid Chromatography-Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Using Matrix Additive Methylenediphosphonic Acid. AB - Mass spectrometry (MS) is a highly sensitive analytical technique that is often coupled with liquid chromatography (LC). However, some buffering salts used in LC (e.g., phosphate and tris(hydroxymethyl)aminomethane (Tris)) are incompatible with MS since they cause ion-source contamination and signal suppression. In this study, we examined salt tolerance of MALDI and applied a matrix additive methylenediphosphonic acid (MDPNA) to reduce salt-induced signal suppression. MDPNA significantly improved the salt tolerance of MALDI-MS. Using ammonium formate buffer at pH 5.0, the effective range of buffering salt concentration in MALDI-MS using MDPNA was estimated up to 250 mM. MDPNA reduced signal suppression caused by buffering salts at pH 4.0 to 8.0. We observed that MDPNA effectively worked over a wide range of buffer conditions. MDPNA was further applied to hydrophilic interaction chromatography (HILIC) and chromatofocusing-MALDI-MS. As a result, the analytes in the eluent containing high-concentration salts were detected with high sensitivity. Thus, our study provides simple and fast LC-MALDI MS analysis technique not having strict limitation of buffering condition in LC by using matrix additive MDPNA. PMID- 26819874 TI - Activation of Nitrogen-Fixing Endophytes Is Associated with the Tuber Growth of Sweet Potato. AB - Endophytic nitrogen-fixing organisms have been isolated from the aerial parts of field-grown sweet potato (Ipomoea batatas). The (15)N dilution method, which is based on the differences in stable nitrogen isotope ratios, is useful for measuring nitrogen fixation in the field. In this study, seedlings of two sweet potato cultivars, 'Beniazuma' and 'Benikomachi,' were transplanted into an alluvial soil that had been treated with organic improving material in advance. Whole plants were sampled every 2 or 3 weeks. After separating plants into tuberous roots and leaves, the fresh weights of the samples were measured, and the nitrogen content and natural (15)N content of leaves were determined with an elemental analyzer and an isotope ratio mass spectrometer linked to an elemental analyzer, respectively. The contribution of nitrogen fixation derived from atmospheric N2 in sweet potato was calculated by assuming that leaves at 2 weeks after transplanting were in a non-nitrogen-fixing state. The contribution ratios of nitrogen fixation by nitrogen-fixing endophytes in leaves of both sweet potato cultivars increased rapidly from 35 to 61 days after transplanting and then increased gradually to 55-57% at 90 days after transplanting. Over the course of the sweet potato growing season, the activity of nitrogen-fixing endophytes in leaves began to increase at about 47 days after transplanting, the weight of leaves increased rapidly, and then growth of tuberous roots began a few weeks later. Our findings indicate that nitrogen-fixing endophytes will be activated under inorganic nitrogen-free sweet potato cultivation, allowing for growth of the tuberous roots. PMID- 26819875 TI - High-Throughput Analysis of Sucrose Fatty Acid Esters by Supercritical Fluid Chromatography/Tandem Mass Spectrometry. AB - Supercritical fluid chromatography (SFC) coupled with triple quadrupole mass spectrometry was applied to the profiling of sucrose fatty acid esters (SEs). The SFC conditions (column and modifier gradient) were optimized for the effective separation of SEs. In the column test, a silica gel reversed-phase column was selected. Then, the method was used for the detailed characterization of commercial SEs and the successful analysis of SEs containing different fatty acids. The present method allowed for fast and high-resolution separation of monoesters to tetra-esters within a shorter time (15 min) as compared to the conventional high-performance liquid chromatography. The applicability of our method for the analysis of SEs was thus demonstrated. PMID- 26819876 TI - Automatic Compound Annotation from Mass Spectrometry Data Using MAGMa. AB - The MAGMa software for automatic annotation of mass spectrometry based fragmentation data was applied to 16 MS/MS datasets of the CASMI 2013 contest. Eight solutions were submitted in category 1 (molecular formula assignments) and twelve in category 2 (molecular structure assignment). The MS/MS peaks of each challenge were matched with in silico generated substructures of candidate molecules from PubChem, resulting in penalty scores that were used for candidate ranking. In 6 of the 12 submitted solutions in category 2, the correct chemical structure obtained the best score, whereas 3 molecules were ranked outside the top 5. All top ranked molecular formulas submitted in category 1 were correct. In addition, we present MAGMa results generated retrospectively for the remaining challenges. Successful application of the MAGMa algorithm required inclusion of the relevant candidate molecules, application of the appropriate mass tolerance and a sufficient degree of in silico fragmentation of the candidate molecules. Furthermore, the effect of the exhaustiveness of the candidate lists and limitations of substructure based scoring are discussed. PMID- 26819877 TI - CASMI 2013: Identification of Small Molecules by Tandem Mass Spectrometry Combined with Database and Literature Mining. AB - The Critical Assessment of Small Molecule Identification (CASMI) contest was initiated in 2012 to evaluate manual and automated strategies for the identification of small molecules from raw mass spectrometric data. The authors participated in both category 1 (molecular formula determination) and category 2 (molecular structure determination) of the second annual CASMI contest (CASMI 2013) using slow but effective manual methods. The provided high resolution mass spectrometric data were interpreted manually using a combination of molecular formula calculators, fragment and neutral loss analysis, literature consultation, manual database searches, deductive logic, and experience. The authors submitted correct formulas as lead candidates for 16 of 16 challenges and submitted correct structure solutions as lead candidates for 14 of 16 challenges. One structure submission (Challenge 3) was very close but not exact (N (2) acetylglutaminylisoleucinamide instead of the correct N (2) acetylglutaminylleucinamide). A solution for one (Challenge 13) was not submitted due to an inability to reconcile the provided fragmentation pattern with any known structures with the provided molecular composition. PMID- 26819878 TI - A Data Structure for Rapid Mass Spectral Searching. AB - The combination of partitioning and systematic bond disconnection has been used to identify compounds from accurate-mass fragmentation data. This combination is very effective in excluding wrong answers that occur by chance. However, both processes are CPU intensive. This paper describes a novel data structure for representing molecules in a computer readable format that is conducive to very rapid mass spectral searching while still retaining the advantages of partitioning and systematic bond disconnection. PMID- 26819879 TI - Solving CASMI 2013 with MetFrag, MetFusion and MOLGEN-MS/MS. AB - The second Critical Assessment of Small Molecule Identification (CASMI) contest took place in 2013. A joint team from the Swiss Federal Institute of Aquatic Science and Technology (Eawag) and Leibniz Institute of Plant Biochemistry (IPB) participated in CASMI 2013 with an automatic workflow-style entry. MOLGEN-MS/MS was used for Category 1, molecular formula calculation, restricted by the information given for each challenge. MetFrag and MetFusion were used for Category 2, structure identification, retrieving candidates from the compound databases KEGG, PubChem and ChemSpider and joining these lists pre-submission. The results from Category 1 were used to guide whether formula or exact mass searches were performed for Category 2. The Category 2 results were impressive considering the database size and automated regime used, although these could not compete with the manual approach of the contest winner. The Category 1 results were affected by large m/z and ppm values in the challenge data, where strategies beyond pure enumeration from other participants were more successful. However, the combination used for the CASMI 2013 entries was extremely useful for developing decision-making criteria for automatic, high throughput general unknown (non-target) identification and for future contests. PMID- 26819880 TI - Molecular Formula Identification Using Isotope Pattern Analysis and Calculation of Fragmentation Trees. AB - We present the results of a fully automated de novo approach for identification of molecular formulas in the CASMI 2013 contest. Only results for Category 1 (molecular formula identification) were submitted. Our approach combines isotope pattern analysis and fragmentation pattern analysis and is completely independent from any (spectral and structural) database. We correctly identified the molecular formula for ten out of twelve challenges, being the best automated method competing in this category. PMID- 26819881 TI - Rethinking Mass Spectrometry-Based Small Molecule Identification Strategies in Metabolomics. AB - The CASMI 2013 (Critical Assessment of Small Molecule Identification 2013, http://casmi-contest.org/) contest was held to systematically evaluate strategies used for mass spectrometry-based identification of small molecules. The results of the contest highlight that, because of the extensive efforts made towards the construction of databases and search tools, database-assisted small molecule identification can now automatically annotate some metabolite signals found in the metabolome data. In this commentary, the current state of metabolite annotation is compared with that of transcriptomics and proteomics. The comparison suggested that certain limitations in the metabolite annotation process need to be addressed, such as (i) the completeness of the database, (ii) the conversion between raw data and structure, (iii) the one-to-one correspondence between measured data and correct search results, and (iv) the false discovery rate in database search results. PMID- 26819883 TI - Foreword. PMID- 26819882 TI - Winners of CASMI2013: Automated Tools and Challenge Data. AB - CASMI (Critical Assessment of Small Molecule Identification) is a contest in which participants identify the molecular formula and chemical structure of challenging molecules using blind mass spectra as the challenge data. Seven research teams participated in CASMI2013. The winner of CASMI2013 was the team of Andrew Newsome and Dejan Nikolic, the University of Illinois at Chicago, IL, USA. The team identified 15 among 16 challenge molecules by manually interpreting the challenge data and by searching in-house and public mass spectral databases, and chemical substance and literature databases. MAGMa was selected as the best automated tool of CASMI2013. In some challenges, most of the automated tools successfully identified the challenge molecules, independent of the compound class and magnitude of the molecular mass. In these challenge data, all of the isotope peaks and the product ions essential for the identification were observed within the expected mass accuracy. In the other challenges, most of the automated tools failed, or identified solution candidates together with many false-positive candidates. We then analyzed these challenge data based on the quality of the mass spectra, the dissociation mechanisms, and the compound class and elemental composition of the challenge molecules. PMID- 26819884 TI - Thermodynamic Measurements of Alloys and Compounds by Double Knudsen Cell Mass Spectrometry and Their Application to Materials Processing. AB - For the development and optimization of materials processing a collection of thermodynamic information concerning substances that participate in the reactions is important. One fundamental way to obtain such information is to measure the vapor pressure of gas species under conditions where they are in equilibrium with the condensed phases. Over the past 60 years Knudsen cell mass spectrometry has been used to identify and quantitatively determine gas species at high temperatures. This article describes thermodynamic foundation and examples of measurements in order to demonstrate the use of mass spectrometry focusing on the field of process metallurgy and recycling processes. PMID- 26819885 TI - Complementary Characterization of End Groups in Radically Polymerized Poly(methyl methacrylate) by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry and Pyrolysis-Gas Chromatography-Mass Spectrometry. AB - The end groups in radically polymerized poly(methyl methacrylate) samples with tert-butyl peroxy-2-ethylhexanoate as an aliphatic peroxide initiator and 1 octanethiol as a chain transfer reagent were complementarily characterized by high-resolution matrix assisted laser desorption/ionization (MALDI) spiral time of-flight mass spectrometry (MS) and pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS). The end groups comprised of three types of the initiator fragments and octylthio group originating from the chain transfer agent were confirmed by MALDI-MS measurements. In addition, their quantitative information was obtained by Py-GC-MS. Furthermore, combined with size exclusion chromatographic fractionation, the molar mass dependence of the end groups in the PMMA samples was also examined. It was suggested that the relative content of the octylthio end groups might increase with increase in the molar mass of the fractions. The observed results were interpreted in terms of the polymerization reactions of the PMMA samples. PMID- 26819886 TI - Recent Progress in Presolar Grain Studies. AB - Presolar grains are stardust that condensed in stellar outflows or stellar ejecta, and was incorporated in meteorites. They remain mostly intact throughout the journey from stars to the earth, keeping information of their birthplaces. Studies of presolar grains, which started in 1987, have produced a wealth of information about nucleosynthesis in stars, mixing in stellar ejecta, and temporal variations of isotopic and elemental abundances in the Galaxy. Recent instrumental advancements in secondary ion mass spectrometry (SIMS) brought about the identification of presolar silicate grains. Isotopic and mineralogical investigations of sub-MUm grains have been performed using a combination of SIMS, transmission electron microscopy (TEM) and focused ion beam (FIB) techniques. Two instruments have been developed to study even smaller grains (~50 nm) and measure isotopes and elements of lower abundances than those in previous studies. PMID- 26819887 TI - Application of Ion Mobility-Mass Spectrometry to the Study of Ionic Clusters: Investigation of Cluster Ions with Stable Sizes and Compositions. AB - Stable cluster sizes and compositions have been investigated for cations and anions of ionic bond clusters such as alkali halides and transition metal oxides by ion mobility-mass spectrometry (IM-MS). Usually structural information of ions can be obtained from collision cross sections determined in IM-MS. In addition, we have found that stable ion sizes or compositions were predominantly produced in a total ion mass spectrum, which was constructed from the IM-MS measurement. These stable species were produced as a result of collision induced dissociations of the ions in a drift cell. We have confirmed this result in the sodium fluoride cluster ions, in which cuboid magic number cluster ions were predominantly observed. Next the stable compositions, which were obtained for the oxide systems of the first row transition metals, Ti, Fe, and Co, are characteristic for each of the metal oxide cluster ions. PMID- 26819888 TI - Establishment of a Strategy for the Discovery and Verification of Low-Abundance Biomarker Peptides in Plasma Using Two Types of Stable-Isotope Tags. AB - Serum and plasma contain thousands of different proteins and peptides, which can provide valuable information about the numerous processes that take place within the body. However, detailed analysis of proteins and peptides in serum and plasma remains challenging due to the presence of many high-abundance proteins, the large dynamic range of protein and peptide concentrations, the extensive complexity caused by posttranslational modifications, and considerable individual variability. In particular, detailed analysis and identification of native peptides is extremely difficult due to the tremendous variety of cleavage possibilities and posttranslational modifications, which results in extremely high complexity. Therefore, widely ranging searches based on peptide identification are difficult. Herein, we describe the highly accurate and sensitive quantitative analysis of over 2,500 peptides with the concentration limit of about 10 pM. The strategy combined isobaric tag labeling, amine-reactive 6-plex tandem mass tag labeling, and a modified differential solubilization method for high-yield peptide extraction [Saito, T. et al. J. Electrophoresis 2013 57: 1-9]. Using this strategy, we quantitatively analyzed six pooled plasma samples (three pre-surgery and three post-surgery) to discover potential candidate biomarker peptides of renal cell carcinoma. The concentrations of 27 peptides were found to be altered following surgery. A preliminary validation study was conducted using about 80 plasma samples to demonstrate the possibility that even unidentified potential candidate biomarker peptides can be verified using the isotope tag/dimethyl labeling method. We also discuss technical consideration and potential of this strategy for facilitating native peptide research. PMID- 26819889 TI - Application of Metabolomics for High Resolution Phenotype Analysis. AB - Metabolome, a total profile of whole metabolites, is placed on downstream of proteome. Metabolome is thought to be results of implementation of genomic information. In other words, metabolome can be called as high resolution phenotype. The easiest operation of metabolomics is the integration to the upstream ome information including transcriptome and/or proteome. Those trials have been reported at a certain scientific level. In addition, metabolomics can be operated in stand-alone mode without any other ome information. Among metabolomics tactics, the author's group is particularly focusing on metabolic fingerprinting, in which metabolome information is employed as explanatory variant to evaluate response variant. Metabolic fingerprinting technique is expected not only for analyzing slight difference depending on genotype difference but also for expressing dynamic variation of living organisms. The author introduces several good examples which he performed. Those are useful for easy understanding of the power of metabolomics. In addition, the author mentions the latest technology for analysis of metabolic dynamism. The author's group developed a facile analytical method for semi-quantitative metabolic dynamism. The author introduces the novel method that uses time dependent variation of isotope distribution based on stable isotope dilution. PMID- 26819890 TI - Simultaneous Quantification of Sphingolipids in Small Quantities of Liver by LC MS/MS. AB - Sph, S1P, and Cer, derived from the membrane sphingolipids, act as intracellular and intercellular mediators, involved in various (path) physiological functions. Accordingly, determining the distributions and concentrations of these sphingolipid mediators in body tissues is an important task. Consequently, a method for determination of sphingolipids in small quantities of tissue is required. Sphingolipids analysis has been dependent on improvements in mass spectrometry (MS) technology. Additionally, decomposition of sphingosine-1 phosphate (S1P) in the tissue samples before preparation for MS has hindered analysis. In the present study, a method for stabilization of liver samples before MS preparation was developed using a heat stabilizer (StabilizorTM T1). Then, a LC-MS/MS method using a triple-quadrupole mass spectrometer with a C8 column was developed for simultaneous determination of sphingolipids in small quantities of liver specimens. This method showed good separation and validation results. Separation was performed with a gradient elution of solvent A (5 mmol L( 1) ammonium formate in water, pH 4.0) and solvent B (5 mmol L(-1) ammonium formate in 95% acetonitrile, pH 4.0) at 300 MUL min(-1). The lower limit of quantification was less than 132 pmol L(-1), and this method was accurate (~13.5%) and precise (~7.13%) for S1P analysis. The method can be used to show the tissue distribution of sphingolipids. PMID- 26819891 TI - Recent Advance in Liquid Chromatography/Mass Spectrometry Techniques for Environmental Analysis in Japan. AB - The techniques and measurement methods developed in the Environmental Survey and Monitoring of Chemicals by Japan's Ministry of the Environment, as well as a large amount of knowledge archived in the survey, have led to the advancement of environmental analysis. Recently, technologies such as non-target liquid chromatography/high resolution mass spectrometry and liquid chromatography with micro bore column have further developed the field. Here, the general strategy of a method developed for the liquid chromatography/mass spectrometry (LC/MS) analysis of environmental chemicals with a brief description is presented. Also, a non-target analysis for the identification of environmental pollutants using a provisional fragment database and "MsMsFilter," an elemental composition elucidation tool, is presented. This analytical method is shown to be highly effective in the identification of a model chemical, the pesticide Bendiocarb. Our improved micro-liquid chromatography injection system showed substantially enhanced sensitivity to perfluoroalkyl substances, with peak areas 32-71 times larger than those observed in conventional LC/MS. PMID- 26819892 TI - Development of Non-proximate Probe Electrospray Ionization for Real-Time Analysis of Living Animal. AB - Ambient ionization mass spectrometry is one of the most challenging analytical tools in the field of biomedical research. We previously demonstrated that probe electrospray ionization mass spectrometry (PESI-MS) could potentially be used in the rapid diagnosis of cancer. Although this technique does not require a tedious sample pretreatment process, it was not possible for our previously reported setup to be applied to cases involving the direct sampling of tissues from living animal and large animal subjects, because there would not be enough room to accommodate the larger bodies juxtaposed to the ion inlet. To make PESI-MS more applicable for the real-time analysis of living animals, a long auxiliary ion sampling tube has been connected to the ion inlet of the mass spectrometer to allow for the collection of ions and charged droplets from the PESI source (hereafter, referred to as non-proximate PESI). Furthermore, an additional ion sampling tube was connected to a small diaphragm pump to increase the uptake rate of air carrying the ions and charged droplets to the ion inlet. This modification allows for the extended ion sampling orifice to be positioned closer to the specimens, even when they are too large to be placed inside the ionization chamber. In this study, we have demonstrated the use of non-proximate PESI-MS for the real-time analysis for biological molecules and pharmacokinetic parameters from living animals. PMID- 26819893 TI - Imaging Mass Spectrometric Analysis of Neurotransmitters: A Review. AB - Imaging mass spectrometry (IMS) is a toolbox of versatile techniques that enable us to investigate analytes in samples at molecular level. In recent years, IMS, and especially matrix-assisted laser desorption/ionisation (MALDI), has been used to visualise a wide range of metabolites in biological samples. Simultaneous visualisation of the spatial distribution of metabolites in a single sample with little tissue disruption can be considered as one important advantage of MALDI over other techniques. However, several technical hurdles including low concentrations and rapid degradation rates of small molecule metabolites, matrix interference of signals and poor ionisation, need to be addressed before MALDI can be considered as a reliable tool for the analysis of metabolites such as neurotransmitters in brain tissues from different sources including humans. In the present review we will briefly describe current MALDI IMS techniques used to study neurotransmitters and discuss their current status, challenges, as well as future prospects. PMID- 26819894 TI - Application of Tapping-Mode Scanning Probe Electrospray Ionization to Mass Spectrometry Imaging of Additives in Polymer Films. AB - We report the application of tapping-mode scanning probe electrospray ionization (t-SPESI) to mass spectrometry imaging of industrial materials. The t-SPESI parameters including tapping solvent composition, solvent flow rate, number of tapping at each spot, and step-size were optimized using a quadrupole mass spectrometer to improve mass spectrometry (MS) imaging of thin-layer chromatography (TLC) and additives in polymer films. Spatial resolution of approximately 100 MUm was achieved by t-SPESI imaging mass spectrometry using a fused-silica capillary (50 MUm i.d., 150 MUm o.d.) with the flow rate set at 0.2 MUL/min. This allowed us to obtain discriminable MS imaging profiles of three dyes separated by TLC and the additive stripe pattern of a PMMA model film depleted by UV irradiation. PMID- 26819895 TI - Analysis of Flexibility of Proteins by means of Positive and Negative Ion MALDI In-Source Decay Mass Spectrometry. AB - The amino acid residues susceptible to in-source decay (ISD) in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry have been identified from both positive and negative ion ISD spectra of cytochrome c, myoglobin, thioredoxin and bovine serum albumin. Backbone cleavages at the N-Calpha bonds of Xxx-Asp, Xxx-Asn, Xxx-Cys, and Gly-Xxx residues gave discontinuous intense peaks of c-ions, independent of positive and negative ion mode. The intensity values for c-ions, Int(c), were defined to allow estimation of the discontinuous intense peaks of c-ions. The identities of the high intensity value residues Asp, Asn, Cys, and Gly were compared with those identified using other measures of flexibility such as the B-factor, turn preferential factor and protection factor. The comparison indicates that Asp, Asn, and Gly residues are common to all measures. Thus, the intensity values of c-ions can be adopted as a measure of protein flexibility. PMID- 26819896 TI - Super-Atmospheric Pressure Ion Sources: Application and Coupling to API Mass Spectrometer. AB - Pressurizing the ionization source to gas pressure greater than atmospheric pressure is a new tactic aimed at further improving the performance of atmospheric pressure ionization (API) sources. In principle, all API sources, such as ESI, APCI and AP-MALDI, can be operated at pressure higher than 1 atm if suitable vacuum interface is available. The gas pressure in the ion source can have different role for different ionization. For example, in the case of ESI, stable electrospray could be sustained for high surface tension liquid (e.g., pure water) under super-atmospheric pressure, owing to the absence of electric discharge. Even for nanoESI, which is known to work well with aqueous solution, its stability and sensitivity were found to be enhanced, particularly in the negative mode when the ion source was pressurized. For the gas phase ionization like APCI, measurement of gaseous compound also showed an increase in ion intensity with the ion source pressure until an optimum pressure at around 4-5 atm. The enhancement was due to the increased collision frequency among reactant ion and analyte that promoted the ion/molecule reaction and a higher intake rate of gas to the mass spectrometer. Because the design of vacuum interface for API instrument is based on the upstream pressure of 1 atm, some coupling aspects need to be considered when connecting the high pressure ion source to the mass spectrometer. Several coupling strategies are discussed in this paper. PMID- 26819897 TI - Separation of Isobaric Compounds Using a Spiral Orbit Type Time-of-Flight Mass Spectrometer, MALDI-SpiralTOF. AB - The development of a MALDI-TOF mass spectrometer that utilizes spiral ion trajectory, SpiralTOF, is reported. The total flight path length was 17 m, which is five times longer than that in commonly used reflectron ion optical system. The SpiralTOF reduced the dependence of the mass resolving power on the mass of the analyte, while improving the accuracy of the mass measurements. Furthermore, SpiralTOF has two advantages that can be exploited for the separation of minor abundant isobaric components in mass spectra. One is the reduction in chemical background due to the post source decay (PSD), which is achieved through PSD ion elimination by electrostatic sectors contained within the SpiralTOF. The other is that the stabilities of peak positions are improved during mass spectrum accumulation. The peak drift caused by the fine structure of matrix crystals and the small irregularities on the sample surface can be reduced by extending the flight path. In this study, these advantages are demonstrated via the analysis of a block copolymer and mass spectrometry imaging (MSI) of lipids. PMID- 26819898 TI - Recent Development of Mass Spectrometric Technologies in Asia and Oceania. PMID- 26819899 TI - Silver Oxide Based Nanoparticle Assisted Laser Desorption/Ionization Mass Spectrometry for the Detection of Low Molecular Weight Compounds. AB - A specific property of silver oxide-based nanoparticles permits the ionization of an analyte, giving rise to various applications of a smart analytical methodology. The nanoparticles (d=6.7 nm) contained an Ag2O core. The detection of several model componds (a nucleobase and two hair growth promoters) via the use of silver oxide nanoparticles is described. Adducts were produced between the target molecules and the two silver stable isotopes (Ag(107) and Ag(109)), resulting in the formation of specific signals as well as a protonated signal. Thus, it was possible to easily determine whether the given signals were correlated with the target molecule or not. PMID- 26819900 TI - Electrospray Ionization on Solid Substrates. AB - Development of electrospray ionization on solid substrates (solid-substrate ESI) avoids the clogging problem encountered in conventional capillary-based ESI, allows more convenient sampling and permits new applications. So far, solid substrate ESI with various materials, e.g., metals, paper, wood, fibers and biological tissue, has been developed, and applications ranging from analysis of pure compounds to complex mixtures as well as in vivo study were demonstrated. Particularly, the capability of solid-substrate ESI in direct analysis of complex samples, e.g., biological fluids and foods, has significantly facilitated mass spectrometric analysis in real-life applications and led to increasingly important roles of these techniques nowadays. In this review, various solid substrate ESI techniques and their applications are summarized and the prospects in this field are discussed. PMID- 26819901 TI - Effective Sample Preparations in Imaging Mass Spectrometry. AB - Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) can be used to visualize the distribution of biomolecules (proteins, peptides, metabolites) and drugs on tissue surfaces. In MALDI-IMS, sample preparation is crucial for successful results. A variety of conditions, such as tissue sampling methods, tissue thickness and matrix application procedure can have an impact on the results. In this review, we summarize each sample preparation step in an orderly sequence with practical examples. In addition, we discuss the importance of the organic solvent used in the matrix solution. The composition of the organic solvent used in the matrix solution is critical for achieving a high sensitivity in this procedure. PMID- 26819902 TI - Study of Isobaric Interference in Quantification of Citrulline by Parallel Fragmentation Monitoring. AB - Parallel Fragmentation Monitoring (PFM), which is an analogue of selected reaction monitoring (SRM), is a recently developed method for quantification of small molecules by MALDI-TOF/TOF mass spectrometry (MS). It is well known that isobaric interference substances can be occasionally present in complex biological samples, and affect the accuracy of measurement by SRM. Unfortunately, by design it is not possible to assess whether isobaric interference happens in a SRM analysis. In contrast, the unique design of PFM should allow quick inspection for isobaric interference and subsequent correction. In this study, using arginine as an example, interference effect of isobaric structural analogs on the quantification of citrulline by PFM was evaluated. Our results showed that the presence of arginine affected the measured concentrations of citrulline standard solutions in a concentration dependent manner. Such interference could be observed readily in the MS/MS spectra, and contributed by [arginine+H-NH3](+) fragment ion. Because of having highly similar mass, (13)C-isotope of [arginine+H NH3](+) fragment ion overlapped with monoisotope of [citrulline+H-NH3](+) fragment ion, which was used as the report ion for quantification. However, such interference could be mathematically eliminated or minimized through estimation of the signal intensity of the (13)C-isotopic peak of [arginine+H-NH3](+) from the intensity of the corresponding monoisotopic peak according to isotope distribution of elements. Furthermore, the presence of interfering fragment ions could be avoided by optimizing MALDI ionization condition. In conclusion, isobaric interference can happen in PFM, but can be easily identified in the mass spectra and eliminated (minimized) with simple methods. PMID- 26819903 TI - Chiral Differentiation of Amino Acids by In-Source Collision-Induced Dissociation Mass Spectrometry. AB - Chiral recognition of d- and l-amino acids is achieved by a method combining electrospray ionization (ESI) and in-source collision-induced dissociation (CID) mass spectrometry (MS). Trimeric cluster ions [Cu(II)(A)(ref)2-H](+) are formed by ESI of mixtures of d- or l-analyte amino acid (A), chiral reference (ref) and CuSO4. By increasing the applied voltage in the ESI source region, the trimeric ions become unstable and dissociate progressively. Thus chiral differentiation of the analyte can be achieved by comparing the dependence of their relative intensities to a reference ion on applied voltages. The method does not need MS/MS technique, thus can be readily performed on single-stage MS instruments by turning the voltage of sampling cone. PMID- 26819904 TI - Increasing the Performance of Portable Ion Mobility Analyzers: Development of the Periodic Focusing Differential Mobility Analyzer (PFDMA). AB - Ion mobility spectrometry (IMS) as a stand-alone technique has become increasingly important for applications in security, defense, and environmental monitoring, and also in biological applications such as molecular structure and omic analysis when combined with mass spectrometry. Yet, the majority of these devices are drift cell based and limited by low duty cycles because of ion gating. Differential Mobility Analyzers (DMAs) are attractive alternatives due to their continuous ion transmission and success in analyzing aerosol particles in real time environmental tests. But, the resolution of a DMA is low due to difficulties in achieving laminar gas flow, low sample gas flow to sheath gas flow ratio, and high velocity sheath gas using small pumps, if portability is a concern. To overcome these challenges, we will introduce a new ion mobility spectrometer that increases the amount of work done on the ions during separation by introducing an electric field opposing the gas flow direction while simultaneously preserving laminar gas flow. The development of the Periodic Focusing Differential Mobility Analyzer (PFDMA) can lead to a portable device that exhibits both high resolution and sensitivity, to meet the needs of today's expanding applications. PMID- 26819905 TI - Multi-Component Profiling of Trace Volatiles in Blood by Gas Chromatography/Mass Spectrometry with Dynamic Headspace Extraction. AB - A dynamic headspace extraction method (DHS) with high-pressure injection is described. This dynamic extraction method has superior sensitivity to solid phase micro extraction, SPME and is capable of extracting the entire gas phase by purging the headspace of a vial. Optimization of the DHS parameters resulted in a highly sensitive volatile profiling system with the ability to detect various volatile components including alcohols at nanogram levels. The average LOD for a standard volatile mixture was 0.50 ng mL(-1), and the average LOD for alcohols was 0.66 ng mL(-1). This method was used for the analysis of volatile components from biological samples and compared with acute and chronic inflammation models. The method permitted the identification of volatiles with the same profile pattern as in vitro oxidized lipid-derived volatiles. In addition, the concentration of alcohols and aldehydes from the acute inflammation model samples were significantly higher than that for the chronic inflammation model samples. The different profiles between these samples could also be identified by this method. Finally, it was possible to analyze alcohols and low-molecular-weight volatiles that are difficult to analyze by SPME in high sensitivity and to show volatile profiling based on multi-volatile simultaneous analysis. PMID- 26819906 TI - Characterization of Mycolic Acids in Total Fatty Acid Methyl Ester Fractions from Mycobacterium Species by High Resolution MALDI-TOFMS. AB - Mycolic acids (MAs) are characteristic components of bacteria in the suborder Corynebacterineae, such as Mycobacterium. MAs are categorized into subclasses based on their functional bases (cyclopropane ring, methoxy, keto, and epoxy group). Since MAs have heterogeneity among bacterial species, analyzing of MAs are required in the chemotaxonomic field. However, their structural analysis is not easy because of their long carbon-chain lengths and several functional groups. In this study, total fatty acid (FA) methyl ester (ME) fraction of M. tuberculosis H37Rv was analyzed by matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOFMS) with a spiral ion trajectory (MALDI spiral-TOFMS). The distributions of carbon-chain length and their relative peak intensities were confirmed with those obtained by analysis of each subclass fraction which was separated from total FA ME fraction using thin-layer chromatography (TLC). The observed major peaks were reliably assigned as MAs owing to the high mass accuracy (error<3 ppm). The types of MA subclasses, their distributions of carbon-chain lengths, their relative peak intensities, and the ratio of even- and odd-numbered carbon-chain MAs for the total FA ME fraction were consistent with those of MA subclass fractions. To visualize whole MAs, contour maps of relative peak intensities for whole MAs were created. The contour maps indicated the MA subclasses and their distributions of carbon-chains with relative peak intensities at a glance. Our proposed method allows simple characterization in a short time and thus enables the analysis of large numbers of samples, and it would contribute to the chemotaxonomy. PMID- 26819907 TI - Method for the Compound Annotation of Conjugates in Nontargeted Metabolomics Using Accurate Mass Spectrometry, Multistage Product Ion Spectra and Compound Database Searching. AB - Owing to biotransformation, xenobiotics are often found in conjugated form in biological samples such as urine and plasma. Liquid chromatography coupled with accurate mass spectrometry with multistage collision-induced dissociation provides spectral information concerning these metabolites in complex materials. Unfortunately, compound databases typically do not contain a sufficient number of records for such conjugates. We report here on the development of a novel protocol, referred to as ChemProphet, to annotate compounds, including conjugates, using compound databases such as PubChem and ChemSpider. The annotation of conjugates involves three steps: 1. Recognition of the type and number of conjugates in the sample; 2. Compound search and annotation of the deconjugated form; and 3. In silico evaluation of the candidate conjugate. ChemProphet assigns a spectrum to each candidate by automatically exploring the substructures corresponding to the observed product ion spectrum. When finished, it annotates the candidates assigning a rank for each candidate based on the calculated score that ranks its relative likelihood. We assessed our protocol by annotating a benchmark dataset by including the product ion spectra for 102 compounds, annotating the commercially available standard for quercetin 3 glucuronide, and by conducting a model experiment using urine from mice that had been administered a green tea extract. The results show that by using the ChemProphet approach, it is possible to annotate not only the deconjugated molecules but also the conjugated molecules using an automatic interpretation method based on deconjugation that involves multistage collision-induced dissociation and in silico calculated conjugation. PMID- 26819908 TI - MALDI Matrix Research for Biopolymers. AB - Matrices are necessary materials for ionizing analytes in matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS). The choice of a matrix appropriate for each analyte controls the analyses. Thus, in some cases, development or improvement of matrices can become a tool for solving problems. This paper reviews MALDI matrix research that the author has conducted in the recent decade. It describes glycopeptide, carbohydrate, or phosphopeptide analyses using 2,5-dihydroxybenzoic acid (2,5-DHB), 1,1,3,3 tetramethylguanidinium (TMG) salts of p-coumaric acid (CA) (G3CA), 3 aminoquinoline (3-AQ)/alpha-cyano-4-hydroxycinnamic acid (CHCA) (3-AQ/CHCA) or 3 AQ/CA and gengeral peptide, peptide containing disulfide bonds or hydrophobic peptide analyses using butylamine salt of CHCA (CHCAB), 1,5-diaminonaphthalene (1,5-DAN), octyl 2,5-dihydroxybenzoate (alkylated dihydroxybenzoate, ADHB), or 1 (2,4,6-trihydroxyphenyl)octan-1-one (alkylated trihydroxyacetophenone, ATHAP). PMID- 26819909 TI - Probe Heating Method for the Analysis of Solid Samples Using a Portable Mass Spectrometer. AB - We previously reported on the development of a portable mass spectrometer for the onsite screening of illicit drugs, but our previous sampling system could only be used for liquid samples. In this study, we report on an attempt to develop a probe heating method that also permits solid samples to be analyzed using a portable mass spectrometer. An aluminum rod is used as the sampling probe. The powdered sample is affixed to the sampling probe or a droplet of sample solution is placed on the tip of the probe and dried. The probe is then placed on a heater to vaporize the sample. The vapor is then introduced into the portable mass spectrometer and analyzed. With the heater temperature set to 130 degrees C, the developed system detected 1 ng of methamphetamine, 1 ng of amphetamine, 3 ng of 3,4-methylenedioxymethamphetamine, 1 ng of 3,4-methylenedioxyamphetamine, and 0.3 ng of cocaine. Even from mixtures consisting of clove powder and methamphetamine powder, methamphetamine ions were detected by tandem mass spectrometry. The developed probe heating method provides a simple method for the analysis of solid samples. A portable mass spectrometer incorporating this method would thus be useful for the onsite screening of illicit drugs. PMID- 26819910 TI - Middle-Down and Chemical Proteomic Approaches to Reveal Histone H4 Modification Dynamics in Cell Cycle: Label-Free Semi-Quantification of Histone Tail Peptide Modifications Including Phosphorylation and Highly Sensitive Capture of Histone PTM Binding Proteins Using Photo-Reactive Crosslinkers. AB - Mass spectrometric proteomics is an effective approach for identifying and quantifying histone post-translational modifications (PTMs) and their binding proteins, especially in the cases of methylation and acetylation. However, another vital PTM, phosphorylation, tends to be poorly quantified because it is easily lost and inefficiently ionized. In addition, PTM binding proteins for phosphorylation are sometimes resistant to identification because of their variable binding affinities. Here, we present our efforts to improve the sensitivity of detection of histone H4 tail peptide phosphorylated at serine 1 (H4S1ph) and our successful identification of an H4S1ph binder candidate by means of a chemical proteomics approach. Our nanoLC-MS/MS system permitted semi quantitative label-free analysis of histone H4 PTM dynamics of cell cycle synchronized HeLa S3 cells, including phosphorylation, methylation, and acetylation. We show that H4S1ph abundance on nascent histone H4 unmethylated at lysine 20 (H4K20me0) peaks from late S-phase to M-phase. We also attempted to characterize effects of phosphorylation at H4S1 on protein-protein interactions. Specially synthesized photoaffinity bait peptides specifically captured 14-3-3 proteins as novel H4S1ph binding partners, whose interaction was otherwise undetectable by conventional peptide pull-down experiments. This is the first report that analyzes dynamics of PTM pattern on the whole histone H4 tail during cell cycle and enables the identification of PTM binders with low affinities using high-resolution mass spectrometry and photo-affinity bait peptides. PMID- 26819911 TI - Development of an Imaging Mass Spectrometry Technique for Visualizing Localized Cellular Signaling Mediators in Tissues. AB - In vivo concentrations of cellular signaling mediators such as inflammatory mediators are normally maintained at very low levels due to their strong ability to induce a biological response. The production, diffusion, and decomposition of such mediators are spatio-temporally regulated. Therefore, in order to understand biochemical basis of disease progression and develop new therapeutic strategies, it is important to understand the spatiotemporal dynamics of the signaling mediators in vivo, during the progression of disorders, e.g., chronic inflammatory diseases; however, the lack of effective imaging technology has made it difficult to determine their localizations in vivo. Such characterization requires technical breakthroughs, including molecular imaging methods that are sensitive enough to detect low levels of metabolites in the heterogeneous tissue regions in diseased organs. We and other groups have attempted to fill this technical gap by developing highly sensitive imaging mass spectrometry (IMS) technologies. To date, we have established two key techniques toward this goal, including (i) a sample preparation procedure that has eliminated the problem of the postmortem degradation of labile metabolites, and (ii) on-tissue derivatization of metabolites, which can enhance analyte ionization efficiency. Here, we review recent progress in the development of these technologies as well as how the highly sensitive IMS technique has contributed to increasing understanding of the biochemical basis of disease mechanisms, discovery of new diagnostic markers, and development of new therapies. PMID- 26819913 TI - Conifer-Derived Monoterpenes and Forest Walking. AB - Conifer and broadleaf trees emit volatile organic compounds in the summer. The major components of these emissions are volatile monoterpenes. Using solid phase microextraction fiber as the adsorbant, monoterpenes were successfully detected and identified in forest air samples. Gas chromatography/mass chromatogram of monoterpenes in the atmosphere of a conifer forest and that of serum from subjects who were walking in a forest were found to be similar each other. The amounts of alpha-pinene in the subjects became several folds higher after forest walking. The results indicate that monoterpenes in the atmosphere of conifer forests are transferred to and accumulate in subjects by inhalation while they are exposed to this type of environment. PMID- 26819912 TI - When API Mass Spectrometry Meets Super Atmospheric Pressure Ion Sources. AB - In a tutorial paper on the application of free-jet technique for API-MS, John Fenn mentioned that "...for a number of years and a number of reasons, it has been found advantageous in many situations to carry out the ionization process in gas at pressures up to 1000 Torr or more" (Int. J. Mass Spectrom. 200: 459-478, 2000). In fact, the first ESI mass spectrometer constructed by Yamashita and Fenn had a counter-flow curtain gas source at 1050 Torr (ca. 1.4 atm) to sweep away the neutral (J. Phys. Chem. 88: 4451-4459, 1984). For gaseous ionization using electrospray plume, theoretical analysis also shows that "super-atmospheric operation would be more preferable in space-charge-limited situations."(Int. J. Mass Spectrom. 300: 182-193, 2011). However, electrospray and the corona-based chemical ion source (APCI) in most commercial instrument are basically operated under an atmospheric pressure ambient, perhaps out of the concern of safety, convenience and simplicity in maintenance. Running the ion source at pressure much higher than 1 atm is not so common, but had been done by a number of groups as well as in our laboratory. A brief review on these ion sources will be given in this paper. PMID- 26819914 TI - A Heuristic Framework for Image Filtering and Segmentation: Application to Blood Vessel Immunohistochemistry. AB - The blood vessel density in a cancerous tissue sample may represent increased levels of tumor growth. However, identifying blood vessels in the histological (tissue) image is difficult and time-consuming and depends heavily on the observer's experience. To overcome this drawback, computer-aided image analysis frameworks have been investigated in order to boost object identification in histological images. We present a novel algorithm to automatically abstract the salient regions in blood vessel images. Experimental results show that the proposed framework is capable of deriving vessel boundaries that are comparable to those demarcated manually, even for vessel regions with weak contrast between the object boundaries and background clutter. PMID- 26819916 TI - Effects of Environmental Factors on Soluble Expression of a Humanized Anti-TNF alpha scFv Antibody in Escherichia coli. AB - PURPOSE: The bacterial cultivation conditions for obtaining anti-TNF-alpha single chain variable fragment (scFv) antibody as the soluble product in E. coli was investigated. METHODS: To avoid the production of inclusion bodies, the effects of lactose, IPTG, incubation time, temperature, shaking protocol, medium additives (Mg+2, sucrose), pH, osmotic and heat shocks were examined. Samples from bacterial growth conditions with promising results of soluble expression of GST-hD2 scFv were affinity purified and quantified by SDS-PAGE and image processing for further evaluation. RESULTS: The results showed that cultivation in LB medium under induction by low concentrations of lactose and incubation at 10 degrees C led to partial solubilization of the expressed anti-TNF-alpha scFv (GST-hD2). Other variables which showed promising increase in soluble expression of GST-hD2 were osmotic shock and addition of magnesium chloride. Furthermore, addition of sucrose to medium suppressed the expression of scFv completely. The other finding was that the addition of sorbitol decreased the growth rate of bacteria. CONCLUSION: It can be concluded that low cultivation temperature in the presence of low amount of inducer under a long incubation time or addition of magnesium chloride are the most effective environmental factors studied for obtaining the maximum solubilization of GST-hD2 recombinant protein. PMID- 26819915 TI - A Review of Molecular Mechanisms Involved in Toxicity of Nanoparticles. AB - In recent decades, the use of nanomaterials has received much attention in industrial and medical fields. However, some reports have mentioned adverse effects of these materials on the biological systems and cellular components. There are several major mechanisms for cytotoxicity of nanoparticles (NPs) such as physicochemical properties, contamination with toxic element, fibrous structure, high surface charge and radical species generation. In this review, a brief key mechanisms involved in toxic effect of NPs are given, followed by the in vitro toxicity assays of NPs and prooxidant effects of several NPs such as carbon nanotubes, titanium dioxide NPs, quantum dots, gold NPs and silver NPs. PMID- 26819917 TI - Short-Term Treatment with Silymarin Improved 6-OHDA-Induced Catalepsy and Motor Imbalance in Hemi-Parkisonian Rats. AB - PURPOSE: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by disabling motor abnormalities, which include tremor, muscle stiffness, paucity of voluntary movements, and postural instability. Silymarin (SM) or milk thistle extract, is known to own antioxidative, anti-apoptotic, anti inflammatory and neuroprotective effects. In the present study, we investigated the effect of intraperitoneal (i.p) administration of SM, on 6-OHDA-induced motor impairments (catalepsy and imbalance) in the rats. METHODS: Experimental model of PD was induced by unilateral infusion of 6-hydroxydopamine (6-OHDA; 8 MUg/2 MUl/rat) into the central region of the substantia nigra pars compacta (SNc). Catalepsy and motor coordination were assessed by using of bar test and rotarod respectively. RESULTS: The results showed a significant (p<0.001) increase in catalepsy of 6-OHDA-lesioned rats whereas; in SM (100, 200 and 300 mg/kg, i.p for 5 days) treated hemi-parkinsonian rats catalepsy was decreased markedly (p<0.001). Furthermore, there was a significant (p<0.001) increase in motor imbalance of 6-OHDA-lesioned rats. SM improved motor coordination significantly (p<0.001) in a dose dependent manner and increased motor balance. CONCLUSION: In conclusion, we found that short-term treatment with SM could improve 6-OHDA induced catalepsy and motor imbalance in rats. We suggest that SM can be used as adjunctive therapy along with commonly used anti-parkinsonian drugs. However, further clinical trial studies should be carried out to prove this hypothesis. PMID- 26819919 TI - Investigation on the Binding Mode of 3, 4-Dihydropyrano[c]Chromene Derivative with Double Strand DNA. AB - PURPOSE: The study on the interaction between small molecules and DNA has been very useful for investigating the structure and physical properties of DNA, elucidating the damage mechanism of DNA and significant in the design of new drugs targeted to DNA. This article describes an interaction of native calf thymus DNA (ctDNA) with a new 3, 4-dihydropyrano[c]chromene derivative, 2-amino-4 (4- chlorophenyl)-5-oxo-4H, 5H-pyrano-[3, 2-c] chromene-3-carbonitrile (4-CC) by using spectroscopic and viscometric techniques. METHODS: The interaction between 4-CC and ctDNA is realized from the UV absorption spectrophotometry, viscosimetry, circular dichroism and fluorescence spectroscopic techniques which shows that the successive interaction of 4-CC with ctDNA occurs. RESULTS: The experimental results revealed that 4-CC can interact with DNA through non- intercalative mode and the intrinsic binding constant (Kb) for 4-CC with DNA was estimated to 2.37 (+/-0.001) *103 M-1. Methylene blue (MB) displacement studies revealed that 4-CC did not have any effect on MB bound DNA which is indicative of groove binding mode. Furthermore, 4-CC induces detectable changes in the CD spectrum of ctDNA as well as changes in its viscosity study corroborate the above experimental results. CONCLUSION: These results further advance our knowledge on the molecular aspects on the interaction of 4-CC to nucleic acids. PMID- 26819918 TI - Clofarabine Has Apoptotic Effect on T47D Breast Cancer Cell Line via P53R2 Gene Expression. AB - PURPOSE: Clofarabine, a purine nucleoside analogue and inhibitor of Ribonucleotide Reductase (RR), is used for treatment of leukemia. Clofarabine induced defect in DNA replication, induces p53 and subsequently P53R2 genes as subunit of RR. clofarabine deregulated P53R2 gene expression leading to the elevated levels of P53R2 which impose resistance to DNA damaging drugs. In this study the apoptotic and cytotoxic effects of clofarabine has been investigated on breast cancer cell line. METHODS: Cofarabine cytotoxicity on T47D cells has been studied by MTT assay. T47D cells were exposed to the different concentrations of clofarabine for 24, 48 and 72 hours intervals. Relative expression of P53R2 gene has been studied using real-time PCR. Moreover, after treating with clofarabine the apoptotic and necrotic cells were detected using Annexin V and propodium iodide (PI) reagents by flowcytometry technique. RESULTS: MTT assay results showed that the clofarabine IC50 on T47D cell line were 3 and 2.5uM after 48 and 72 h exposure, respectively. Clofarabine did not show any significant cytotoxic effect after 24 h exposure. The analysis of qRT-PCR showed a significant increase in P53R2 gene expression in treated cells with both 2.5 and 3 MUM doses and also, the results of flowcytometry revealed 26.91 and 74.46 percent apoptosis induction in 48 and 72h treatments respectively in comparison to the control groups. CONCLUSION: Our results showed that apoptotic and cytotoxic effects of clofarabine on T47D cell line were in time and dose dependent manner; therefore it could be considered a new candidate in breast cancer therapy. PMID- 26819920 TI - Ethosuximide Affects Paired-Pulse Facilitation in Somatosensory Cortex of WAG?Rij Rats as a Model of Absence Seizure. AB - PURPOSE: The interaction between somatosensory cortex and thalamus via a thalamocortical loop is a theory behind induction of absence epilepsy. Inside peri-oral somatosensory (S1po) and primary somatosensory forelimb (S1fl) regions, excitatory and inhibitory systems are not balanced and GABAergic inhibitory synapses seem to play a fundamental role in short-term plasticity alterations. METHODS: We investigated the effects of Ethosuximide on presynaptic changes by utilizing paired-pulse stimulation that was recorded from somatosensory cortex in 18 WAG?Rij rats during epileptic activity. A twisted tripolar electrode including two stimulating electrodes and one recording electrode was implanted into the S1po and S1FL according to stereotaxic landmarks. Paired-pulses (200 us, 100-1000 uA, 0.1 Hz) were applied to somatosensory cortex at 50, 100, 400, 500 ms inter pulse intervals for 50 min period. RESULTS: The results showed that paired-pulse facilitation was significantly reduced at all intervals in all times, but compared to the control group of epileptic WAG/Rij rats (p<0.05), it was exceptional about the first 10 minutes after the injection. At the intervals of 50 and 100 ms, a remarkable PPD was found in second, third, fourth and fifth 10 min post injection. CONCLUSION: These experiments indicate that Ethosuximide has effects on presynaptic facilitation in somatosensory cortex inhibitory loops by alteration in GABA levels that leads to a markedly diminished PPF in paired-pulse stimulation. PMID- 26819921 TI - Effect of Buspirone, Fluoxetine and 8-OH-DPAT on Striatal Expression of Bax, Caspase-3 and Bcl-2 Proteins in 6-Hydroxydopamine-Induced Hemi-Parkinsonian Rats. AB - PURPOSE: The exact pathogenesis of sporadic parkinson's disease (PD) is still unclear. Numerous evidences suggest involvement of apoptosis in the death of dopaminergic neurons. In this study we investigated the effect of sub-chronic administration of buspirone, fluoxetine and 8-hydroxy-2-[di-n propylamino]tetralin (8-OH-DPAT) in 6-hydroxydopamine (6-OHDA)-lesioned rats and assayed striatal concentrations of apoptotic (Bax, Caspase3) and anti-apoptotic (Bcl-2) proteins. METHODS: 6-OHDA (8MUg/2MUl/rat) was injected unilaterally into the central region of the substantia nigra pars copmacta (SNc) of male Wistar rats and then, after 21 days lesioned rats were treated with intraperitonel (i.p) 1 mg/kg injections of buspirone, fluoxetine and 8-OH-DPAT for 10 consecutive days. Striatum of rats was removed at tenth day of drugs administration and were analyzed by western blotting method to measure Bax, caspase3 and Bcl-2 expression. RESULTS: The results showed that the expression of Bax and caspase3 proteins was increased three weeks after 6-OHDA injection while they were decreased significantly in parkinsonian rats which were treated by buspirone, fluoxetine and 8-OH-DPAT. Bcl-2 was decreased and increased in parkinsonian rats and parkinsonian rats treated with buspirone, fluoxetine and 8-OH-DPAT, respectively. CONCLUSION: Our study indicates that sub-chronic administration of serotonergic drugs such as buspirone, fluoxetine and 8-OH-DPAT restores striatal concentration of apoptotic and anti-apoptotic factors to the basal levels of normal non-lesioned rats. We suggest that these drugs can be used as a potential adjunctive therapy in PD through attenuating neuronal apoptotic process. PMID- 26819922 TI - Preventing Aggregation of Recombinant Interferon beta-1b in Solution by Additives: Approach to an Albumin-Free Formulation. AB - PURPOSE: Aggregation suppressing additives have been used to stabilize proteins during manufacturing and storage. Interferonbeta-1b is prone to aggregation because of being non-glycosylated. Aggregation behavior of albumin-free formulations of recombinant IFNbeta-1b was explored using additives such as n dodecyl-beta-D-maltoside, Tween 20, arginine, glycine, trehalose and sucrose at different pH. METHODS: Fractional factorial design was applied to select major factors affecting aggregation in solutions. Box-Behnken technique was used to optimize the best concentration of additives and protein. RESULTS: Quadratic model was the best fitted model for particle size, OD350 and OD280/OD260. The optimal conditions of 0.2% n-Dodecyl-beta-D-maltoside, 70 mM arginine, 189 mM trehalose and protein concentration of 0.50 mg/ml at pH 4 were achieved. A potency value of 91% +/- 5% was obtained for the optimized formulation. CONCLUSION: This study shows that the combination of n-Dodecyl-beta-D-maltoside, arginine and trehalose would demonstrate a significant stabilizing and anti aggregating effect on the liquid formulation of interferonbeta-1b. It can not only reduce the manufacturing costs but will also ease patient compliance. PMID- 26819923 TI - A Combination of Prebiotic Inulin and Oligofructose Improve Some of Cardiovascular Disease Risk Factors in Women with Type 2 Diabetes: A Randomized Controlled Clinical Trial. AB - PURPOSE: This trial was conducted to evaluate the effects of oligofructose enriched inulin on some of cardiovascular disease risk factors in women with type 2 diabetes. METHODS: 52 females (25 0.05). However, the mean CSP was longer in IGE patients than in normal controls at all stimulus intensities (p < 0.05). The mean CSP in ipsilateral hemisphere (IH) of FE was significantly longer at all stimulus intensities than that in normal controls (p < 0.001). The CSP in IH was longer than that in the contralateral hemisphere of FE. There was no significant difference in CSP between FE and IGE. SICI was significantly reduced only in the IH of FE versus normal subjects. RMT, MEP amplitudes, and ICF did not differ among IGE, FE, and normal controls. CONCLUSIONS: We found that prolonged CSP and reduced SICI in FE indicate asymmetrically increased cortical inhibition and excitation in the epileptic hemispheres. It suggests that CSP among TMS parameters has a crucial role to lateralize the epileptic hemisphere in FE. PMID- 26819940 TI - Clinical Prediction Rule of Drug Resistant Epilepsy in Children. AB - BACKGROUND AND PURPOSE: Clinical prediction rules (CPR) are clinical decision making tools containing variables such as history, physical examination, diagnostic tests by developing scoring model from potential risk factors. This study is to establish clinical prediction scoring of drug-resistant epilepsy (DRE) in children using clinical manifestationa and only basic electroencephalography (EEG). METHODS: Retrospective cohort study was conducted. A total of 308 children with diagnosed epilepsy were recruited. Primary outcome was the incidence of DRE. Independent determinants were patient characteristics, clinical manifestations and electroencephalography. CPR was performed based on multiple logistic regression. RESULTS: The incidence of DRE was 42%. Risk factors were age onset, prior neurological deficits, and abnormal EEG. CPR can be established and stratified the prediction using scores into 3 levels such as low risk (score<6), moderate risk (score 6-12) and high risk (score>12) with positive likelihood ratio of 0.5, 1.8 and 12.5 respectively. CONCLUSIONS: CPR with scoring risks were stratified into 3 levels. The strongest risk is prior global neurological deficits. PMID- 26819941 TI - Safety and Efficacy of Zonisamide in Patients with Epilepsy: A Post-Marketing Surveillance Study. AB - BACKGROUND AND PURPOSE: Zonisamide (ZNS) is one of new antiepileptic drug, which is known to inhibit seizure through multiple mechanisms of action. In Korea, ZNS was approved as an antiepileptic drug in 1992 and has been used for epilepsy patients with partial and generalized seizures. The objective of this study was to investigate the efficacy and tolerability of ZNS in patients with epilepsy and to identify the incidence of adverse events in real clinical setting. METHODS: This study was carried out in patients who received ZNS for epilepsy. Patients who were observed for at least 12 weeks after treatment with ZNS were included as evaluable subjects. Information regarding the status and type of adverse events occurring during the course of treatment with ZNS was obtained regardless of causal relationship to ZNS and efficacy was assessed by the study physicians and patients at 12 weeks post dose of ZNS. RESULTS: A total of 1,948 patients were included in the study, and ZNS efficacy was evaluated in 1,744 patients. ZNS was used as a monotherapy in 1,095 patients and as an adjunctive drug in 853 patients. Of the total patients, 1,345 (69.1%) patients had partial seizure, 563 patients had generalized seizure, and 40 patients were undetermined. Adverse events were reported in 65 patients (3.34%) including 1 case of Stevens-Johnson syndrome, but no incidence of serious unexpected adverse drug reactions were reported. 755 patients (43.29%) became seizure free with ZNS treatment, and additional 322 patients (18.41%) experienced marked improvement with ZNS treatment. CONCLUSIONS: Our study shows the safety and tolerability of ZNS treatment in patients with epilepsy in real clinical setting. In addition, ZNS was found to be an effective option as a monotherapy or in patients with generalized seizure. PMID- 26819942 TI - Long-Term Migration of a Deep Brain Stimulation (DBS) Lead in the Third Ventricle Caused by Cerebral Atrophy in a Patient with Anterior Thalamic Nucleus DBS. AB - The long-term (5-years) antiepileptic effect of deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) against refractory epilepsy has been reported. However, experience with ANT DBS for epilepsy is limited, and so hardware complications and technical problems related to ANT DBS are unclear. We report the case of a 57-year-old male who underwent re-implantation of a DBS lead in the left ANT because of lead migration into the third ventricle detected 8 years after the first DBS, and which was caused by the significant enlargement of the lateral and third ventricles. After re-implantation, the patient showed a mechanically-related antiepileptic effect and a prominent driving response of the electroencephalography was verified. We speculate that progressive dilatation of the ventricle and shallow, insufficient implantation of the lead during the initial ANT DBS may have caused migration of the DBS lead. Because dilatation of the ventricle could progress years after DBS in a patient with chronic epilepsy, regular follow-up imaging is warranted in ANT DBS patients with an injured, atrophied brain. PMID- 26819943 TI - Transient Positive Horizontal Head Impulse Test in Pregabalin Intoxication. AB - Head impulse test (HIT) is helpful to understanding high-frequency vestibulo ocular reflex in patients with dizziness and imbalance. There are some reports on abnormal HITs in cerebellar disorder. To our knowledge, there was no report of transient bilateral positive head impulse related to antiepileptic drugs. A 65 year-old woman developed dizziness and imbalance after treatment with pregabalin for pain control of radiation cystitis. Neurological examination exhibited positive bilateral HIT results, in addition to ataxia and gaze-evoked rebound nystagmus. Pregabalin intoxication can evoke transient positive horizontal head impulse test as another indicator of cerebellar dysfunction. PMID- 26819944 TI - Ginkgotoxin Induced Seizure Caused by Vitamin B6 Deficiency. AB - Although ginkgo is commonly used as an alternative treatment for memory loss, Alzheimer's dementia and peripheral circulatory disturbances, it is also known to cause neuronal symptoms due to ginkgotoxin (4'-methoxypyridoxine or B6 antivitamin). We experienced a case of a 51-year-old female patient with generalized tonic clonic seizure and postictal confusion after eating large amounts of ginkgo nuts. Blood vitamin B6 level was decreased. After conservative treatment and pyridoxine medication, her mental symptoms were resolved completely and no seizures recurred. PMID- 26819946 TI - Practical Calling Approach for Exome Array-Based Genome-Wide Association Studies in Korean Population. AB - Exome-based genotyping arrays are cost-effective and have recently been used as alternative platforms to whole-exome sequencing. However, the automated clustering algorithm in an exome array has a genotype calling problem in accuracy for identifying rare and low-frequency variants. To address these shortcomings, we present a practical approach for accurate genotype calling using the Illumina Infinium HumanExome BeadChip. We present comparison results and a statistical summary of our genotype data sets. Our data set comprises 14,647 Korean samples. To solve the limitation of automated clustering, we performed manual genotype clustering for the targeted identification of 46,076 variants that were identified using GenomeStudio software. To evaluate the effects of applying custom cluster files, we tested cluster files using 804 independent Korean samples and the same platform. Our study firstly suggests practical guidelines for exome chip quality control in Asian populations and provides valuable insight into an association study using exome chip. PMID- 26819945 TI - Targeted Mybpc3 Knock-Out Mice with Cardiac Hypertrophy Exhibit Structural Mitral Valve Abnormalities. AB - MYBPC3 mutations cause hypertrophic cardiomyopathy, which is frequently associated with mitral valve (MV) pathology. We reasoned that increased MV size is caused by localized growth factors with paracrine effects. We used high resolution echocardiography to compare Mybpc3-null, heterozygous, and wild-type mice (n = 84, aged 3-6 months) and micro-CT for MV volume (n = 6, age 6 months). Mybpc3-null mice showed left ventricular hypertrophy, dilation, and systolic dysfunction compared to heterozygous and wild-type mice, but no systolic anterior motion of the MV or left ventricular outflow obstruction. Compared to wild-type mice, echocardiographic anterior leaflet length (adjusted for left ventricular size) was greatest in Mybpc3-null mice (1.92 +/- 0.08 vs. 1.72 +/- 0.08 mm, p < 0.001), as was combined leaflet thickness (0.23 +/- 0.04 vs. 0.15 +/- 0.02 mm, p < 0.001). Micro-CT analyses of Mybpc3-null mice demonstrated increased MV volume (0.47 +/- 0.06 vs. 0.15 +/- 0.06 mm3, p = 0.018) and thickness (0.35 +/- 0.04 vs. 0.12 +/- 0.04 mm, p = 0.002), coincident with increased markers of TGFbeta activity compared to heterozygous and wild-type littermates. Similarly, excised MV from a patient with MYBPC3 mutation showed increased TGFbeta activity. We conclude that MYBPC3 deficiency causes hypertrophic cardiomyopathy with increased MV leaflet length and thickness despite the absence of left ventricular outflow tract obstruction, in parallel with increased TGFbeta activity. MV changes in hypertrophic cardiomyopathy may be due to paracrine effects, which represent targets for therapeutic studies. PMID- 26819947 TI - Mental Health Services in Rural China: A Qualitative Study of Primary Health Care Providers. AB - This study aimed to understand the challenges that primary health care providers faced in the process of delivering mental healthcare and assess their attitudes towards patients with mental health problems. In-depth interviews were conducted among 42 primary health care providers in two counties of Guangxi province, China. All interviews were audio-recorded and analyzed thematically. Primary health care providers in both counties faced the same difficulties: lack of professional knowledge, fear of patients' attack, more extra work, and less subsidies. However, most of primary health care providers (30/42) were still willing to do mental healthcare management. All the interviewees considered that communication skills with patients and their family members, proper attitude (without discrimination), and the professional knowledge of mental health are required. There are still several participants (15/42) who showed negative attitude toward mental disorders. Nearly all the respondents (39/42) emphasized the importance of increasing their income or subsidies by the government. This qualitative study provides insights into mental health services in rural communities of Guangxi and identified issues that could be considered in engaging primary health care providers in the management of mental disorders. PMID- 26819948 TI - Immediate Radical Cystectomy for Massive Bleeding of Bladder Cancer. AB - OBJECTIVE: To investigate feasibility and safety of our surgical strategy and clinical and oncological efficacy. MATERIALS AND METHODS: In a high volume tertiary institution 225 radical cystectomies were performed from January 2012 to December 2014. We prospectively collected data of a cohort of 12 patients who underwent immediate open radical cystectomy for bladder cancer causing massive haematuria, acute anemia, and impossibility of postponing surgery. A retrospective study was carried out to evaluate operative data, intra- and postoperative complications, and oncologic outcomes. The Clavien-Dindo Classification was used to grade complications. The oncologic outcome was evaluated in terms of positive overall and soft tissue surgical margins and cancer specific survival at a median follow-up of 26 months. RESULTS: Mean preoperative haemoglobin was 6.8 mg/dL. Mean operative time was 278 minutes. Mean blood loss was 633 mL. The overall transfusion rate was 100% with a mean of 3.6 blood units per patient before surgery and 1.8 units postoperatively. No intraoperative complications occurred. Major complications (defined as grades III, IV, and V according to Clavien-Dindo Classification) were 18,5%. In fact grade III complications were 14.8% and grade IV complications were 3.7%. Grade V did not occur. The positive surgical margin rate was 33.3% and cancer specific survival was 58,3% at median follow-up of 26 months. CONCLUSIONS: Immediate surgical management seems feasible, safe, and efficacious. PMID- 26819949 TI - Hypoxia-Induced Epithelial-Mesenchymal Transition Is Involved in Bleomycin Induced Lung Fibrosis. AB - Pulmonary fibrosis is a severe disease that contributes to the morbidity and mortality of a number of lung diseases. However, the molecular and cellular mechanisms leading to lung fibrosis are poorly understood. This study investigated the roles of epithelial-mesenchymal transition (EMT) and the associated molecular mechanisms in bleomycin-induced lung fibrosis. The bleomycin induced fibrosis animal model was established by intratracheal injection of a single dose of bleomycin. Protein expression was measured by Western blot, immunohistochemistry, and immunofluorescence. Typical lesions of lung fibrosis were observed 1 week after bleomycin injection. A progressive increase in MMP-2, S100A4, alpha-SMA, HIF-1alpha, ZEB1, CD44, phospho-p44/42 (p-p44/42), and phospho p38 MAPK (p-p38) protein levels as well as activation of EMT was observed in the lung tissues of bleomycin mice. Hypoxia increased HIF-1alpha and ZEB1 expression and activated EMT in H358 cells. Also, continuous incubation of cells under mild hypoxic conditions increased CD44, p-p44/42, and p-p38 protein levels in H358 cells, which correlated with the increase in S100A4 expression. In conclusion, bleomycin induces progressive lung fibrosis, which may be associated with activation of EMT. The fibrosis-induced hypoxia may further activate EMT in distal alveoli through a hypoxia-HIF-1alpha-ZEB1 pathway and promote the differentiation of lung epithelial cells into fibroblasts through phosphorylation of p38 MAPK and Erk1/2 proteins. PMID- 26819950 TI - Status of Human Papillomavirus Infection in the Ethnic Population in Yunnan Province, China. AB - HPV genotypes have distinct distributions among various ethnic populations worldwide. In December 2013, 237 and 159 cervical samples were collected from Hani and Han ethnic women, respectively, in Mojiang, a rural county in southern Yunnan. The overall HPV infection rate (21.1%) among the Hani women was significantly higher than that among the Han women (12.6%). The high-risk (HR) and low-risk (LR) HPV and single- and multiple-genotype infection rates among the Hani women were 11.0%, 4.6%, 15.6%, and 5.5%, respectively. HPV-16 (3.8%) was the most prevalent genotype among the Hani women, followed by HPV-52 (1.7%), HPV-31 (0.8%), and HPV-33 (0.8%). Comparatively, the Han women had lower infection rates of high-risk (8.2%), low-risk (1.2%), single-genotype (9.4%), and multiple genotype HPV infections (3.1%). HPV-16 (3.1%) was also the predominant genotype among the Han women, followed by HPV-52 (1.3%), HPV-33 (0.6%), HPV-44 (0.6%), and HPV-54 (0.6%). The area background, number of children, and past history of STIs were recognized as potential risk factors for HPV infection. Rural background, age, education level, number of children, and illness history were significantly associated with HPV infection among the Hani women. These findings highlight the urgent need for HPV prevention and control strategies in Yunnan, particularly for the Hani ethnic women. PMID- 26819952 TI - Impact of pH Management Interval on Biohydrogen Production from Organic Fraction of Municipal Solid Wastes by Mesophilic Thermophilic Anaerobic Codigestion. AB - The biohydrogen productions from the organic fraction of municipal solid wastes (OFMSW) were studied under pH management intervals of 12 h (PM12) and 24 h (PM24) for temperature of 37 +/- 0.1 degrees C and 55 +/- 0.1 degrees C. The OFMSW or food waste (FW) along with its two components, noodle waste (NW) and rice waste (RW), was codigested with sludge to estimate the potential of biohydrogen production. The biohydrogen production was higher in all reactors under PM12 as compared to PM24. The drop in pH from 7 to 5.3 was observed to be appropriate for biohydrogen production via mesophilic codigestion of noodle waste with the highest biohydrogen yield of 145.93 mL/g CODremoved under PM12. When the temperature was increased from 37 degrees C to 55 degrees C and pH management interval was reduced from 24 h to 12 h, the biohydrogen yields were also changed from 39.21 mL/g COD removed to 89.67 mL/g COD removed, 91.77 mL/g COD removed to 145.93 mL/g COD removed, and 15.36 mL/g COD removed to 117.62 mL/g COD removed for FW, NW, and RW, respectively. The drop in pH and VFA production was better controlled under PM12 as compared to PM24. Overall, PM12 was found to be an effective mean for biohydrogen production through anaerobic digestion of food waste. PMID- 26819951 TI - Temporal Trends and Predictors of Modern Contraceptive Use in Lusaka, Zambia, 2004-2011. AB - INTRODUCTION: Although increasing access to family planning has been an important part of the global development agenda, millions of women continue to face unmet need for contraception. MATERIALS AND METHODS: We analyzed data from a repeated cross-sectional community survey conducted in Lusaka, Zambia, over an eight-year period. We described prevalence of modern contraceptive use, including long acting reversible contraception (LARC), among female heads of household aged 16 50 years. We also identified predictors of LARC versus short-term contraceptive use among women using modern methods. RESULTS AND DISCUSSION: Twelve survey rounds were completed between November 2004 and September 2011. Among 29,476 eligible respondents, 17,605 (60%) reported using modern contraception. Oral contraceptive pills remained the most popular method over time, but use of LARC increased significantly, from less than 1% in 2004 to 9% by 2011 (p < 0.001). Younger women (OR: 0.46, 95% CI: 0.34, 0.61) and women with lower levels of education (OR: 0.70, 95% CI: 0.56, 0.89) were less likely to report LARC use compared to women using short-term modern methods. CONCLUSIONS: Population-based assessments of contraceptive use over time can guide programs and policies. To achieve reproductive health equity and reduce unmet contraceptive need, future efforts to increase LARC use should focus on young women and those with less education. PMID- 26819953 TI - Kinesio Taping Does Not Alter Quadriceps Isokinetic Strength and Power in Healthy Nonathletic Men: A Prospective Crossover Study. AB - OBJECTIVES: The effects of Kinesio Taping (KT) on muscular performance remain largely unclear. This study aimed to investigate the acute effects of KT on the maximum concentric and eccentric quadriceps isokinetic strength. STUDY DESIGN: This is a single-blinded, placebo crossover, repeated measures study. METHODS: Maximum isokinetic concentric/eccentric extension torque, work, and power were assessed by an isokinetic dynamometer without taping (NT) and with KT or placebo taping (PT) in 17 healthy young men. Repeated measures one-way analysis of variance (ANOVA) was used for statistical analyses. RESULTS: Testing concentric contractions at 60 degrees /s or 180 degrees /s isokinetic speed, no significant differences in peak torque (Nm), total work (J), or mean power (W) were noted among the application modes under different conditions. Testing eccentric contractions at 30 degrees /s or 60 degrees /s isokinetic speed, no significant differences in mentioned parameters were noted, respectively. KT on the quadriceps neither decreased nor increased muscle strength in the participants. CONCLUSION: KT application onto the skin overlying the quadriceps muscle does not enhance the strength or power of knee extensors in healthy men. PMID- 26819954 TI - Serial Patterns of Ovarian Cancer Biomarkers in a Prediagnosis Longitudinal Dataset. AB - Early detection of ovarian cancer through screening may have impact on mortality from the disease. Approaches based on CA125 cut-off have not been effective. Longitudinal algorithms such as the Risk of Ovarian Cancer Algorithm (ROCA) to interpret CA125 have been shown to have higher sensitivity and specificity than a single cut-off. The aim of this study was to investigate whether other ovarian cancer-related biomarkers, Human Epididymis 4 (HE4), glycodelin, mesothelin, matrix metalloproteinase 7 (MMP7), and cytokeratin 19 fragment (CYFRA 21-1), could improve the performance of CA125 in detecting ovarian cancer earlier. Serum samples (single and serial) predating diagnosis from 47 women taking part in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) who went on to develop primary invasive ovarian, fallopian tube, or peritoneal cancer (index cancer) (170 samples) and 179 matched controls (893 samples) were included in the study. A multiplex immunobased assay platform (Becton Dickinson) allowing simultaneous measurement of the six serum markers was used. The area under the ROC curve for the panel of three biomarkers (CA125, HE4, and glycodelin) was higher than for CA125 alone for all analysed time groups, indicating that these markers can improve on sensitivity of CA125 alone for ovarian cancer detection. PMID- 26819955 TI - Phytochemical Screening and Acute Oral Toxicity Study of Java Tea Leaf Extracts. AB - The term Java tea refers to the decoction of Orthosiphon stamineus (OS) Benth (Lamiaceae) leaves, which are widely consumed by the people in Europe and South East Asian countries. The OS leaves are known for their use in traditional medicinal systems as a prophylactic and curative agent for urinary stone, diabetes, and hypertension and also as a diuretic agent. The present study was aimed at evaluating its possible toxicity. Herein, the major phytochemical constituents of microwave dried OS leaf, which is the common drying process for tea sachets in the market, were also identified. The acute oral toxicity test of aqueous, 50% aqueous ethanolic, and ethanolic extracts of OS was performed at a dose of 5000 mg/Kg body weight of Sprague-Dawley rats. During the 14-day study, the animals were observed for any mortality, behavioral, motor-neuronal abnormalities, body weight, and feed-water consumption pattern. The hematological and serum biochemical parameters to assess the kidney and liver functions were carried out, along with the histological analysis of these organs. It was found that all microwave dried OS leaf extracts did not cause any toxic effects or mortality at the administered dose. No abnormality was noticed in all selected parameters in rats of both sexes as compared with their respective control groups. Thus, the possible oral lethal dose for microwave dried Java tea leaves is more than 5000 mg/Kg body weight. PMID- 26819956 TI - Immunoregulation of NKT Cells in Systemic Lupus Erythematosus. AB - Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with different variety of clinical manifestations. Natural killer T (NKT) cells are innate lymphocytes that play a regulatory role during broad range of immune responses. A number of studies demonstrated that the quantity and quality of invariant NKT (iNKT) cells showed marked defects in SLE patients in comparison to healthy controls. This finding suggests that iNKT cells may play a regulatory role in the occurrence and development of this disease. In this review, we mainly summarized the most recent findings about the behavior of NKT cells in SLE patients and mouse models, as well as how NKT cells affect the proportion of T helper cells and the production of autoreactive antibodies in the progress of SLE. This will help people better understand the role of NKT cells in the development of SLE and improve the therapy strategy. PMID- 26819957 TI - Towards Targeted Delivery Systems: Ligand Conjugation Strategies for mRNA Nanoparticle Tumor Vaccines. AB - The use of nanoparticles encapsulating messenger RNA (mRNA) as a vaccine has recently attracted much attention because of encouraging results achieved in many nonviral genetic antitumor vaccination studies. Notably, in all of these studies, mRNA nanoparticles are passively targeted to dendritic cells (DCs) through careful selection of vaccination sites. Hence, DC-targeted mRNA nanoparticle vaccines may be an imminent next step forward. In this brief report, we will discuss established conjugation strategies that have been successfully applied to both polymeric and liposomal gene delivery systems. We will also briefly describe promising DC surface receptors amenable for targeting mRNA nanoparticles. Practicable conjugation strategies and receptors reviewed in this paper will provide a convenient reference to facilitate future development of targeted mRNA nanoparticle vaccine. PMID- 26819958 TI - Heparin Interaction with the Primed Polymorphonuclear Leukocyte CD11b Induces Apoptosis and Prevents Cell Activation. AB - Heparin is known to have anti-inflammatory effects, yet the mechanisms are not completely understood. In this study, we tested the hypothesis that heparin has a direct effect on activated polymorphonuclear leukocytes (PMNLs), changing their activation state, and can explain its anti-inflammatory effect. To test our hypothesis, we designed both in vitro and ex vivo studies to elucidate the mechanism by which heparin modulates PMNL functions and therefore the inflammatory response. We specifically tested the hypothesis that priming of PMNLs renders them more susceptible to heparin. Amplified levels of CD11b and increased rate of superoxide release manifested PMNL priming. Increase in cell priming resulted in a dose-dependent increase in heparin binding to PMNLs followed by augmented apoptosis. Blocking antibodies to CD11b inhibited heparin binding and abolished the apoptotic response. Moreover, heparin caused a significant dose-dependent decrease in the rate of superoxide release from PMNLs, which was blunted by blocking antibodies to CD11b. Altogether, this study shows that the interaction of heparin with the PMNL CD11b results in cell apoptosis and explains heparin's anti-inflammatory effects. PMID- 26819960 TI - Far East Scarlet-Like Fever: A Review of the Epidemiology, Symptomatology, and Role of Superantigenic Toxin: Yersinia pseudotuberculosis-Derived Mitogen A. AB - Far East scarlet-like fever (FESLF) is a severe inflammatory disease that occurs sporadically and in outbreaks in Russia and Japan. Far East scarlet-like fever is caused by Yersinia pseudotubuclosis infection, an organism that typically causes self-limiting gastroenteritis in Europe. Studies suggest the ability of Far Eastern strains to produce superantigen toxin Y pseudotuberculosis-derived mitogen A is integral to FESLF pathogenesis. In Europe, human Y pseudotuberculosis infection typically occurs sporadically, in the form of a self limiting gastroenteritis. In Russia and Japan, outbreaks of Y pseudotuberculosis infection cause severe systemic inflammatory symptoms. This disease variant is called FESLF. Geographical heterogeneity exists between virulence factors produced by European and Far Eastern Y pseudotuberculosis strains, implicating superantigen Y pseudotuberculosis-derived mitogen A (YPMa) in the pathogenesis of FESLF. This article describes the epidemiology and clinical features of FESLF, and it presents the evidence for the role of YPMa in FESLF pathogenesis. PMID- 26819961 TI - Mycoplasma pneumoniae, a trigger for Weston Hurst syndrome. AB - OBJECTIVE: We report a case of Mycoplasma pneumoniae infection as one possible trigger for Weston Hurst syndrome (acute hemorrhagic leukoencephalitis), a rare disorder of microvascular injury often described as a postinfectious complication of an upper respiratory illness. METHODS: This is a case of a 27-year-old man presenting with a Glasgow Coma Scale score of 3 and an acute head CT revealing extensive vasogenic edema in the right hemisphere associated with mass effect in the context of a recent upper respiratory illness. Right frontal biopsy was performed on day 2, which showed acute cerebritis, and the patient was aggressively treated with antibiotics. However, over the next 5 days from presentation, the vasogenic edema increased, leading ultimately to brain herniation and death. RESULTS: A full autopsy was performed at 5 days from presentation, which showed areas of vessel wall fibrinoid necrosis throughout the right hemisphere as well as, but less so, in the left frontal lobe and pons. Chest x-ray on presentation revealed atypical pneumonia, blood tests were positive for cold agglutinins, and at full autopsy, there was myocarditis, all in keeping with recent M pneumoniae infection. DNA obtained from lung and diseased brain (postmortem) was positive for Mycoplasma providing more direct evidence for brain invasion by this organism as the ultimate trigger for Weston Hurst syndrome. CONCLUSIONS: This is a rare case report of Weston Hurst syndrome having both initial brain biopsy on day 2 and full autopsy results on day 5 of presentation revealing important clinical clues about the pathogenesis of this often fatal disorder. PMID- 26819959 TI - Neutrophils in Cancer: Two Sides of the Same Coin. AB - Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of defense during inflammation and infections. In addition, neutrophils are also found infiltrating many types of tumors. Tumor-associated neutrophils (TANs) have relevant roles in malignant disease. Indeed neutrophils may be potent antitumor effector cells. However, increasing clinical evidence shows TANs correlate with poor prognosis. The tumor microenvironment controls neutrophil recruitment and in turn TANs help tumor progression. Hence, TANs can be beneficial or detrimental to the host. It is the purpose of this review to highlight these two sides of the neutrophil coin in cancer and to describe recent studies that provide some light on the mechanisms for neutrophil recruitment to the tumor, for neutrophils supporting tumor progression, and for neutrophil activation to enhance their antitumor functions. PMID- 26819962 TI - Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder. AB - OBJECTIVE: To study rituximab in pediatric neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD) and the relationship between rituximab, B cell repopulation, and relapses in order to improve rituximab monitoring and redosing. METHODS: Multicenter retrospective study of 16 children with NMO/NMOSD receiving >=2 rituximab courses. According to CD19 counts, events during rituximab were categorized as "repopulation," "depletion," or "depletion failure" relapses (repopulation threshold CD19 >=10 * 10(6) cells/L). RESULTS: The 16 patients (14 girls; mean age 9.6 years, range 1.8-15.3) had a mean of 6.1 events (range 1-11) during a mean follow-up of 6.1 years (range 1.6-13.6) and received a total of 76 rituximab courses (mean 4.7, range 2-9) in 42.6-year cohort treatment. Before rituximab, 62.5% had received azathioprine, mycophenolate mofetil, or cyclophosphamide. Mean time from rituximab to last documented B cell depletion and first repopulation was 4.5 and 6.8 months, respectively, with large interpatient variability. Earliest repopulations occurred with the lowest doses. Significant reduction between pre- and post-rituximab annualized relapse rate (ARR) was observed (p = 0.003). During rituximab, 6 patients were relapse-free, although 21 relapses occurred in 10 patients, including 13 "repopulation," 3 "depletion," and 4 "depletion failure" relapses. Of the 13 "repopulation" relapses, 4 had CD19 10-50 * 10(6) cells/L, 10 had inadequate monitoring (<=1 CD19 in the 4 months before relapses), and 5 had delayed redosing after repopulation detection. CONCLUSION: Rituximab is effective in relapse prevention, but B cell repopulation creates a risk of relapse. Redosing before B cell repopulation could reduce the relapse risk further. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that rituximab significantly reduces ARR in pediatric NMO/NMOSD. This study also demonstrates a relationship between B cell repopulation and relapses. PMID- 26819964 TI - For your eyes only: Harnessing human embryonic stem cell-derived retinal pigment epithelial cells to improve impaired vision. AB - Vision loss or impairment resulting from the degeneration of the retinal pigment epithelium and photoreceptor death affects millions worldwide. Recent exciting results from clinical studies of small numbers of patients treated with human embryonic stem cell-derived retinal pigment epithelial cells may provide hope for affected individuals. PMID- 26819963 TI - Alemtuzumab long-term immunologic effect: Treg suppressor function increases up to 24 months. AB - OBJECTIVE: To analyze changes in T-helper (Th) subsets, T-regulatory (Treg) cell percentages and function, and mRNA levels of immunologically relevant molecules during a 24-month follow-up after alemtuzumab treatment in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Multicenter follow-up of 29 alemtuzumab-treated patients with RRMS in the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) I and CARE-MS II trials. Peripheral blood (PB) samples were obtained at months 0, 6, 12, 18, and 24. We evaluated (1) mRNA levels of 26 immunologic molecules (cytokines, chemokines, chemokine receptors, and transcriptional factors); (2) Th1, Th17, and Treg cell percentages; and (3) myelin basic protein (MBP)-specific Treg suppressor activity. RESULTS: We observed 12 relapses in 9 patients. mRNA levels of the anti inflammatory cytokines interleukin (IL)-10, IL-27, and transforming growth factor beta persistently increased whereas those of proinflammatory molecules related to the Th1 or Th17 subsets persistently decreased after alemtuzumab administration throughout the follow-up period. PB CD4+ cell percentage remained significantly lower than baseline while that of Th1 and Th17 cells did not significantly change. A significant increase in Treg cell percentage was observed at month 24 and was accompanied by an increase in Treg cell suppressive activity against MBP specific Th1 and Th17 cells. CONCLUSIONS: The long-lasting therapeutic benefit of alemtuzumab in RRMS may involve a shift in the cytokine balance towards inhibition of inflammation associated with a reconstitution of the PB CD4+ T-cell subsets that includes expansion of Treg cells with increased suppressive function. PMID- 26819965 TI - Damage control: Harnessing prostaglandin E2 as a potential healing factor of tissue injuries. AB - Increasing prostaglandin E2 by knocking out its inhibitor 15-hydroxyprostaglandin dehydrogenase (15-PDGH) or administering a compound that inhibits 15-PDGH was recently found to improve healing in hematopoietic stem cell transplants, colitis recovery, and hepatogenesis after transection in mice. These results are suggestive of pharmacologic therapies or even genetic therapy that could improve patient outcomes, especially since the excess PGE2 and the 15-PDGH inhibitor have proven to be non-toxic. However, elevated levels of PGE2 are associated with increased risk of cancer and blood clotting problems. It would be unacceptable to treat a cancer patient with chemotherapy and replenish the hematopoietic stem cells with the help of PGE2, only to have increased expression of PGE2 and induce another cancer. Therefore, to assess the most therapeutic aspects of PGE2, it is important to consider effects that could induce disease. PMID- 26819966 TI - Energy-Aware Multipath Routing Scheme Based on Particle Swarm Optimization in Mobile Ad Hoc Networks. AB - Mobile ad hoc network (MANET) is a collection of autonomous mobile nodes forming an ad hoc network without fixed infrastructure. Dynamic topology property of MANET may degrade the performance of the network. However, multipath selection is a great challenging task to improve the network lifetime. We proposed an energy aware multipath routing scheme based on particle swarm optimization (EMPSO) that uses continuous time recurrent neural network (CTRNN) to solve optimization problems. CTRNN finds the optimal loop-free paths to solve link disjoint paths in a MANET. The CTRNN is used as an optimum path selection technique that produces a set of optimal paths between source and destination. In CTRNN, particle swarm optimization (PSO) method is primly used for training the RNN. The proposed scheme uses the reliability measures such as transmission cost, energy factor, and the optimal traffic ratio between source and destination to increase routing performance. In this scheme, optimal loop-free paths can be found using PSO to seek better link quality nodes in route discovery phase. PSO optimizes a problem by iteratively trying to get a better solution with regard to a measure of quality. The proposed scheme discovers multiple loop-free paths by using PSO technique. PMID- 26819968 TI - Monoclonal Antibodies That Recognize the Alkylation Signature of Antimalarial Ozonides OZ277 (Arterolane) and OZ439 (Artefenomel). AB - The singular structure of artemisinin, with its embedded 1,2,4-trioxane heterocycle, has inspired the discovery of numerous semisynthetic artemisinin and structurally diverse synthetic peroxide antimalarials, including ozonides OZ277 (arterolane) and OZ439 (artefenomel). Despite the critical importance of artemisinin combination therapies (ACTs), the precise mode of action of peroxidic antimalarials is not fully understood. However, it has long been proposed that the peroxide bond in artemisinin and other antimalarial peroxides undergoes reductive activation by ferrous heme released during hemoglobin digestion to produce carbon-centered radicals that alkylate heme and parasite proteins. To probe the mode of action of OZ277 and OZ439, this paper now describes initial studies with monoclonal antibodies that recognize the alkylation signature (sum of heme and protein alkylation) of these synthetic peroxides. Immunofluorescence experiments conducted with ozonide-treated parasite cultures showed that ozonide alkylation is restricted to the parasite, as no signal was found in the erythrocyte or its membrane. In Western blot experiments with ozonide-treated Plasmodium falciparum malaria parasites, distinct protein bands were observed. Significantly, no protein bands were detected in parallel Western blot experiments performed with lysates from ozonide-treated Babesia divergens, parasites that also proliferate inside erythrocytes but, in contrast to P. falciparum, do not catabolize hemoglobin. However, subsequent immunoprecipitation experiments with these antibodies failed to identify the P. falciparum proteins alkylated by OZ277 and OZ439. To the best of the authors' knowledge, this shows for the first time that antimalarial ozonides, such as the artemisinins, alkylate proteins in P. falciparum. PMID- 26819969 TI - Smartphone Applications for Promoting Healthy Diet and Nutrition: A Literature Review. AB - BACKGROUND: Rapid developments in technology have encouraged the use of smartphones in health promotion research and practice. Although many applications (apps) relating to diet and nutrition are available from major smartphone platforms, relatively few have been tested in research studies in order to determine their effectiveness in promoting health. METHODS: In this article, we summarize data on the use of smartphone applications for promoting healthy diet and nutrition based upon bibliographic searches in PubMed and CINAHL with relevant search terms pertaining to diet, nutrition, and weight loss through August 2015. RESULTS: A total of 193 articles were identified in the bibliographic searches. By screening abstracts or full-text articles, a total of three relevant qualitative studies and 9 randomized controlled trials were identified. In qualitative studies, participants preferred applications that were quick and easy to administer, and those that increase awareness of food intake and weight management. In randomized trials, the use of smartphone apps was associated with better dietary compliance for lower calorie, low fat, and high fiber foods, and higher physical activity levels (p=0.01-0.02) which resulted in more weight loss (p=0.042-<0.0001). DISCUSSION: Future studies should utilize randomized controlled trial research designs, larger sample sizes, and longer study periods to better establish the diet and nutrition intervention capabilities of smartphones. There is a need for culturally appropriate, tailored health messages to increase knowledge and awareness of health behaviors such as healthy eating. Smartphone apps are likely to be a useful and low-cost intervention for improving diet and nutrition and addressing obesity in the general population. Participants prefer applications that are quick and easy to administer and those that increase awareness of food intake and weight management. PMID- 26819967 TI - A Review of the Effects of Major Atmospheric Pollutants on Pollen Grains, Pollen Content, and Allergenicity. AB - This review summarizes the available data related to the effects of air pollution on pollen grains from different plant species. Several studies carried out either on in situ harvested pollen or on pollen exposed in different places more or less polluted are presented and discussed. The different experimental procedures used to monitor the impact of pollution on pollen grains and on various produced external or internal subparticles are listed. Physicochemical and biological effects of artificial pollution (gaseous and particulate) on pollen from different plants, in different laboratory conditions, are considered. The effects of polluted pollen grains, subparticles, and derived aeroallergens in animal models, in in vitro cell culture, on healthy human and allergic patients are described. Combined effects of atmospheric pollutants and pollen grains-derived biological material on allergic population are specifically discussed. Within the notion of "polluen," some methodological biases are underlined and research tracks in this field are proposed. PMID- 26819970 TI - The role of ophthalmology departments in overcoming health care disparities. AB - Ophthalmology departments can play a unique role in providing care for at-risk patients. This study analyzed the age, gender, and socioeconomic measures for 267,286 unique African American patients seen at University of Pennsylvania Health System (UPHS). Patients seen by the Ophthalmology Department (n=33,801) were older and more likely to be from impoverished zip codes than those seen by other UPHS specialists. These results hint at several inherent advantages of ophthalmology departments in recruiting older, disadvantaged patients to their clinics. We found that supplementing this advantage with strong patient relationships, involvement of community leaders, and customized outreach efforts was key to overcoming access-to-care issues and to reaching these patients. This provides ophthalmologists with a unique opportunity to capture and refer systemic conditions with ocular manifestations and to possibly reduce disparities such as post-hospitalization readmission and mortality observed disproportionately in impoverished populations. PMID- 26819973 TI - Obituary. PMID- 26819971 TI - Sirt1 in cerebral ischemia. AB - Cerebral ischemia is among the leading causes of death worldwide. It is characterized by a lack of blood flow to the brain that results in cell death and damage, ultimately causing motor, sensory, and cognitive impairments. Today, clinical treatment of cerebral ischemia, mostly stroke and cardiac arrest, is limited and new neuroprotective therapies are desperately needed. The Sirtuin family of oxidized nicotinamide adenine dinucleotide (NAD+)-dependent deacylases has been shown to govern several processes within the central nervous system as well as to possess neuroprotective properties in a variety of pathological conditions such as Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease, among others. Recently, Sirt1 in particular has been identified as a mediator of cerebral ischemia, with potential as a possible therapeutic target. To gather studies relevant to this topic, we used PubMed and previous reviews to locate, select, and resynthesize the lines of evidence presented here. In this review, we will first describe some functions of Sirt1 in the brain, mainly neurodevelopment, learning and memory, and metabolic regulation. Second, we will discuss the experimental evidence that has implicated Sirt1 as a key protein in the regulation of cerebral ischemia as well as a potential target for the induction of ischemic tolerance. PMID- 26819972 TI - Promoting colorectal cancer screening among Haitian Americans. AB - BACKGROUND: Few studies have examined colorectal cancer screening among Haitian Americans, although striking disparities in colorectal cancer screening and mortality are well-documented among U.S. Blacks. Race, socioeconomic status, and place of birth are factors associated with colorectal cancer incidence and mortality patterns. METHODS: In this article, we summarize published studies on colorectal cancer screening among Haitian Americans, identified through bibliographic searches in PubMed and CINAHL through August 2015, and offer recommendations for further research. RESULTS: Only one qualitative study and three quantitative surveys have examined colorectal cancer screening among Haitian Americans. A qualitative study found important differences in perceptions of the curability of colorectal cancer, preventive practices, and preferred sources of information among Haitian Americans and other ethnic subgroups of U.S. Blacks. Awareness of colorectal cancer screening tests, risk perception, healthcare provider recommendation, and self-reported use of screening are suboptimal among Haitian Americans and other subgroups. In preliminary quantitative studies, Haitian immigrants have been found to have lower colorectal cancer screening rates than other groups such as African Americans. CONCLUSIONS: Culturally appropriate educational interventions are needed to encourage Haitian American adults aged >= 50 years to undergo screening for colorectal cancer and to ensure that they are well informed about the value of healthy eating and physical activity. PMID- 26819974 TI - Reentrant condensation of lysozyme: Implications for studying dynamics of lysozyme in aqueous solutions of lithium chloride. AB - Recent studies have outlined the use of eutectic solutions of lithium chloride in water to study microscopic dynamics of lysozyme in an aqueous solvent that is remarkably similar to pure water in many respects, yet allows experiments over a wide temperature range without solvent crystallization. The eutectic point in a (H2O)R(LiCl) system corresponds to R ~ 7.3, and it is of interest to investigate whether less-concentrated aqueous solutions of LiCl could be used in low temperature studies of a solvated protein. We have investigated a range of concentrations of lysozyme and LiCl in aqueous solutions to identify systems that do not show phase separation and avoid solvent crystallization on cooling down. Compared to the lysozyme concentration in solution, the concentration of LiCl in the aqueous solvent plays the major role in determining systems suitable for low temperature studies. We have observed interesting and rich phase behavior reminiscent of reentrant condensation of proteins. PMID- 26819975 TI - Controlling network topology and mechanical properties of co-assembling peptide hydrogels. AB - Oligopeptides are well-known to self-assemble into a wide array of nanostructures including beta-sheet-rich fibers that when present above a critical concentration become entangled and form self-supporting hydrogels. The length, quantity, and interactions between fibers influence the mechanical properties of the hydrogel formed and this is typically achieved by varying the peptide concentration, pH, ionic strength, or the addition of a second species or chemical cross-linking agent. Here, we outline an alternative, facile route to control the mechanical properties of the self-assembling octa-peptide, FEFEFKFK (FEKII); simply doping with controlled quantities of its double length peptide, FEFEFKFK-GG-FKFKFEFE (FEKII18). The structure and properties of a series of samples were studied here (0-100 M% of FEKII18) using Fourier transform infrared, small angle X-ray scattering, transmission electron microscopy, and oscillatory rheology. All samples were found to contain elongated, flexible fibers and all mixed samples contained Y-shaped branch points and parallel fibers which is attributed to the longer peptide self-assembling within two fibers, thus creating a cross-link in the network structure. Such behavior was reflected in an increase in the elasticity of the mixed samples with increasing quantity of double peptide. Interestingly the elastic modulus increased up to 30 times the pure FEKII value simply by adding 28 M% of FEKII18. These observations provide an easy, off-the shelf method for an end-user to control the cross-linked network structure of the peptide hydrogel, and consequently strength of the hydrogel simply by physically mixing pre-determined quantities of two similar peptide molecules. PMID- 26819976 TI - Influence of the single-strand linker composition on the structural/dynamical properties of a truncated octahedral DNA nano-cage family. AB - The structural/dynamical properties of three truncated octahedral DNA nano-cages composed by identical double helices but single strand linkers with different composition, namely 7 thymidines, 7 adenines, and 7 alternated thymidines and adenines, have been investigated through classical molecular dynamics simulations. Trajectories have been analyzed to investigate the role of the linkers in defining nano-cages stability and flexibility, including possible influence on the internal cages motions. The data indicate that the cages behavior is almost identical and that the structural/dynamical parameters measured along the trajectories are not particularly affected by the presence of different bases. These results demonstrate that the constraints imposed by the nano-structure geometry are the main factor in modulating these properties PMID- 26819977 TI - One Step Forward. PMID- 26819978 TI - Dentists and Health Screenings. PMID- 26819979 TI - Dr. Marshall Responds. PMID- 26819980 TI - TMD Controversy Continues. PMID- 26819981 TI - Drs. Jenkins and Raman Reply. PMID- 26819982 TI - The Ethics Awards. PMID- 26819983 TI - Volunteerism Within Dentistry. PMID- 26819984 TI - Why Volunteerism Works. PMID- 26819985 TI - Volunteerism: Everyone Wins. PMID- 26819986 TI - We Make a Life by What We Give. PMID- 26819987 TI - Volunteering Internationally: Why, Where and How. AB - Oral health volunteers have an important role in addressing oral health care shortages around the world, but to be effective they need to understand and prepare for the challenges of working overseas. PMID- 26819988 TI - International Volunteer Dentistry: A Basic Primer. PMID- 26819989 TI - Sterilization for Large Volunteer Temporary Clinics. AB - Large portable clinics staffed by volunteers present many unique challenges, including establishing appropriate instrument processing services. This article explores many of the specific steps an organization can take to ensure a safe care environment for patients and a safe working environment for volunteers. PMID- 26819990 TI - Ethical Considerations in Volunteer Dental Care. PMID- 26819991 TI - Analyze Risks Before Volunteering. PMID- 26819992 TI - Strategies for a Team Approach to Risk Management. PMID- 26819993 TI - Calling, Texting or Emailing Patients? Know the Rules. PMID- 26819994 TI - The Silver Tsunami. PMID- 26819995 TI - Ethics Sweepstakes. PMID- 26819996 TI - Dentistry for the Ages: Part I. PMID- 26819997 TI - Dental Care in the Frail Older Adult: Special Considerations and Recommendations. AB - Frail older adults disproportionately suffer from untreated dental problems. Age related biological changes to hard and soft dental tissues, existing medical conditions, polypharmacy, diet and uncontrolled plaque exacerbate the problem. All of these factors increase the complexity of treatment and will differ greatly from standard treatment of younger adults. This article discusses the key considerations and suggestions for risk assessment, disease management, treatment planning and palliative care to maintain the patient's comfort and quality of life. PMID- 26819998 TI - Geriatric Dentistry in the 21st Century: Environment and Opportunity. AB - The aging of the baby boomers in the 21st century is creating unprecedented numbers of vulnerable older adults. The increase in people keeping their teeth and their increasingly complex conditions all point to more people with more complex needs. Although these demographic shifts are providing unparalleled challenges for our health care system, they also bring new opportunities to develop and implement innovative systems for reaching and maintaining the oral health of older Americans. PMID- 26819999 TI - Health History Vital in Assessing Patients, Reducing Risk. PMID- 26820000 TI - Radiation Safety Q-and-A. PMID- 26820001 TI - Long in the Tooth. PMID- 26820002 TI - The Spirit of Birth. PMID- 26820003 TI - Bite-Mark Analysis. PMID- 26820004 TI - Dr. Golden responds. PMID- 26820005 TI - Ring of Gyges. PMID- 26820006 TI - Trends in Dentomaxillofacial Imaging. PMID- 26820007 TI - Guide to Digital Radiographic Imaging. AB - This is a resource for clinicians who are considering purchasing a digital imaging system or those already using one who want to optimize its use. It covers selected topics in digital imaging fundamentals, detector technology, image processing and quality assurance. Through a critical appraisal of the strengths and limitations of digital imaging components, the goal of this guide is to contribute to the appropriate use of these systems to maximize the health benefit for patients. PMID- 26820008 TI - Evidence and Professional Guidelines for Appropriate Use of Cone Beam Computed Tomography. AB - Cone beam computed tomography (CBCT) has applications in several aspects of dentistry. To appropriately use this technology, clinicians should be able to identify those situations where the information from CBCT is likely to provide useful information, and where this additional information translates into enhanced diagnoses, treatment plans and treatment outcomes. This article summarizes current evidence and recommendations from professional societies that guide safe and effective use of this technology for enhanced patient care. PMID- 26820009 TI - Cone Beam Computed Tomography for the Dental Implant Patient. AB - Cone beam computed tomography offers many advantages over 2-D imaging for the evaluation of potential implant sites. With the use of CBCT scans becoming more commonplace, it is important for clinicians to be knowledgeable and to use this new technology appropriately and judiciously. The purpose of this article is to describe the advantages and limitations of CBCT imaging for the presurgical and postsurgical evaluations of implant treatment and assessment of implant-related complications. PMID- 26820010 TI - Evaluation of the Upper Airway Morphology: The Role of Cone Beam Computed Tomography. AB - Cone beam computed tomography (CBCT) has several applications in dentomaxillofacial diagnosis. Frequently, the imaged volume encompasses the upper airway. This article provides a systematic approach to airway analysis and the implications of the anatomic and pathologic alterations. It discusses the role of CBCT in management of obstructive sleep apnea (OSA) patients. This paper also highlights technological advances that combine CBCT imaging with computational modeling of the airway and the potential clinical applications of such technologies. PMID- 26820011 TI - When Casual Behavior Crosses the Professional Line. PMID- 26820012 TI - Patient Rights Under HIPAA. PMID- 26820013 TI - [A FETUS FROM VARNA WITH A CYSTIC HYGROMA OF THE NECK]. AB - The cystic hygroma of the neck in fetuses is a congenital anomaly, usually detected by ultrasound during the prenatal morphological study. It is a rare anomaly that is diagnosed relatively easy by an examination of the nuchal fold. The frequency of the cystic hygroma in the world is approximately 1/6000 live births, but there is no data for diagnosed cases in Bulgaria. The purpose of this work is to present a case of cystic hygroma of the neck in a fetus from Varna, Bulgaria. The method used is an autopsy. The fetus is female, weighing 250g, the result of a spontaneous abortion during the 19th gestational week. RESULTS: The autopsy found a cystic bilocular hygroma of the neck and a unilateral ptosis of the kidney CONCLUSION: The cystic hygroma of the neck can be isolated, but it is often associated with trisomy 21 or with other malformation syndromes, which confirms the importance of morphological examinations of the neck during the prenatal ultrasound. PMID- 26820014 TI - Total Chemical Synthesis of an Orf Virus Protein, ORFV002, an Inhibitor of the Master Gene Regulator NF-kappaB. AB - ORFV002 is a novel orf viral protein (117 Aa) that inhibits nuclear events through the regulation of the transcriptional activity of NF-kappaB, a master regulator of human gene expression (Diel et al., J Virol 2011, 85, 264-275). It is identified as the first nuclear inhibitor of NF-kappaB produced by orf virus (ORFV) and no homologues in other genera of the Chordopoxvirinae subfamily have been reported to date (Diel et al., J Virol 2011, 85, 264-275). Our molecular structure predictions suggest that ORFV002 may mimic part of IkappaB, an inhibitor and natural human partner of NF-kappaB. Recent advances in total chemical synthesis of proteins have provided solutions in overcoming challenges of current recombinant methods of protein isolation for structure elucidation. Aided by Boc solid phase peptide synthesis and native chemical ligation, ORFV002 was successfully synthesized in multimilligram amounts in good yield and high purity. PMID- 26820015 TI - Surface Display of Small Peptides on Escherichia coli for Enhanced Calcite Precipitation Rates. AB - Mineralization has emerged as a promising strategy for long-term carbon sequestration. These processes involve carbon dioxide hydration followed by mineral precipitation. We have explored the production of whole-cell biocatalysts engineered with carbonic anhydrase (CA) activity to accelerate the CO2 hydration reaction. In this study, short polypeptides were displayed on the surface of E. coli cells and whole-cell biocatalysts containing periplasmically expressed CAs in an attempt to enhance calcite mineral formation. It was found that cells coexpressing recombinant periplasmic CA and surface-displayed GPA peptide (PEVPEGAFDTAI) outperformed other peptide-expressing biocatalysts evaluated in terms of the amount of precipitate formed, as well as the overall formation rate of solids. Cells expressing the Cab CA isoform (BLR-pCab) and Cam isoform (BLR pCam) with the surface-displayed GPA peptide exhibited 36 and 59% improvements in precipitation amounts, as well as 18 and 60% improvements in overall formation rates, respectively, over similar biocatalysts without GPA expression. The biocatalyst with the best performance was BLR-pCam/GPA, which generated 0.15 g of CaCO3, while BLR cells generated only 0.08 g of CaCO3 under the same small batch reaction conditions. The BLR-pCam/GPA cells also exhibited the fastest formation rates, achieving the maximum change in solution turbidity after only 2.2 min, as opposed to 6.3 min for BLR cells. These results demonstrate that synthetic biology approaches can be used to create novel biocatalysts with the ability to enhance both catalysis and precipitation activities. PMID- 26820016 TI - Navigating Hormones and Gynecologic Concerns among Female Adolescents in the Settings of Thrombophilia and Anticoagulation. AB - In the setting of an inherited or acquired thrombophilia, managing a gynecologic concern can be challenging. Nonetheless, careful consideration of the history along with a team approach to management, in which hematologists and gynecologists work together is critical. Thombophilias are important to understand, because certain types pose more risk than others. In addition, it is important to balance baseline factors, which might affect decisions regarding the best way to manage a concurrent gynecologic condition. Relative risks for thrombosis have been well studied for a variety of inherited and acquired conditions. Because of these risks, organizations such as the Centers for Disease Control and Prevention, World Health Organization, and American College of Obstetricians and Gynecologists have compiled clinical guidance recommendations to aid providers when hormonal management might be necessary (ie, to treat conditions such as delayed puberty, ovarian cysts, heavy menstrual bleeding, contraception). It is important to use these resources because there are limited prospective studies on this specific population who present with concurrent gynecologic conditions. PMID- 26820017 TI - Breastfeeding. Foreword. PMID- 26820018 TI - The results should be compared with a gold standard diagnostic test--the author responds. PMID- 26820038 TI - Solid Electrolyte Lithium Phosphous Oxynitride as a Protective Nanocladding Layer for 3D High-Capacity Conversion Electrodes. AB - Materials that undergo conversion reactions to form different materials upon lithiation typically offer high specific capacity for energy storage applications such as Li ion batteries. However, since the reaction products often involve complex mixtures of electrically insulating and conducting particles and significant changes in volume and phase, the reversibility of conversion reactions is poor, preventing their use in rechargeable (secondary) batteries. In this paper, we fabricate and protect 3D conversion electrodes by first coating multiwalled carbon nanotubes (MWCNT) with a model conversion material, RuO2, and subsequently protecting them with conformal thin-film lithium phosphous oxynitride (LiPON), a well-known solid-state electrolyte. Atomic layer deposition is used to deposit the RuO2 and the LiPON, thus forming core double-shell MWCNT@RuO2@LiPON electrodes as a model system. We find that the LiPON protection layer enhances cyclability of the conversion electrode, which we attribute to two factors. (1) The LiPON layer provides high Li ion conductivity at the interface between the electrolyte and the electrode. (2) By constraining the electrode materials mechanically, the LiPON protection layer ensures electronic connectivity and thus conductivity during lithiation/delithiation cycles. These two mechanisms are striking in their ability to preserve capacity despite the profound changes in structure and composition intrinsic to conversion electrode materials. This LiPON-protected structure exhibits superior cycling stability and reversibility as well as decreased overpotentials compared to the unprotected core-shell structure. Furthermore, even at very low lithiation potential (0.05 V), the LiPON-protected electrode largely reduces the formation of a solid electrolyte interphase. PMID- 26820039 TI - High-Frequency (13)C and (29)Si NMR Chemical Shifts in Diamagnetic Low-Valence Compounds of Tl(I) and Pb(II): Decisive Role of Relativistic Effects. AB - The (13)C and (29)Si NMR signals of ligand atoms directly bonded to Tl(I) or Pb(II) heavy-element centers are predicted to resonate at very high frequencies, up to 400 ppm for (13)C and over 1000 ppm for (29)Si, outside the typical experimental NMR chemical-shift ranges for a given type of nuclei. The large (13)C and (29)Si NMR chemical shifts are ascribed to sizable relativistic spin orbit effects, which can amount to more than 200 ppm for (13)C and more than 1000 ppm for (29)Si, values unexpected for diamagnetic compounds of the main group elements. The origin of the vast spin-orbit contributions to the (13)C and (29)Si NMR shifts is traced to the highly efficient 6p -> 6p* metal-based orbital magnetic couplings and related to the 6p orbital-based bonding together with the low-energy gaps between the occupied and virtual orbital subspaces in the subvalent Tl(I) and Pb(II) compounds. New NMR spectral regions for these compounds are suggested based on the fully relativistic density functional theory calculations in the Dirac-Coulomb framework carefully calibrated on the experimentally known NMR data for Tl(I) and Pb(II) complexes. PMID- 26820040 TI - Oxidative (3 + 2) Cycloaddition Reactions of Diaza-Oxyallyl Cationic Intermediates and Indoles for the Synthesis of Imidazoloindolines. AB - An oxidative diaza-(3 + 2) cycloaddition reaction of simple urea derivatives with substituted indoles has been developed. This transformation provides rapid access to highly functionalized imidazoloindolines that are represented in bioactive compounds. The reported method is compatible with a wide variety of functional groups and directly provides unique heterocyclic scaffolds from indoles and a simple urea derivative. PMID- 26820041 TI - Solution-Binding and Molecular Docking Approaches Combine to Provide an Expanded View of Multidrug Recognition in the MDR Gene Regulator BmrR. AB - Solution-binding and molecular docking have been combined with a diverse collection of chemical probes to further elucidate multidrug (MD) recognition in BmrR. Whereas previous efforts have focused on structural elucidations of MD binding, the present study examines features imparted by structure, including the recognition properties of the ligand-pocket, ligand structural requirements, and key factors that define and influence binding. Whereas MD-pockets are generally believed to be featureless and very hydrophobic, log KD-clog P correlations observed for BmrR and other polyspecific proteins suggest polar contributions are required for broad-spectrum recognition of amphipathic ligands. We show that molecular docking simulations recapitulate key features of MD recognition and have been employed to further inform contributions from structure. In addition to elaborating our understanding of the structures and functional roles of pocket elements that dictate broad-spectrum binding, molecular docking has implication additional features that likely play major roles, including ligand dynamics and multiple ligand-binding modes. PMID- 26820042 TI - Disseminated superficial actinic porokeratosis improved with fractional 1927-nm laser treatments. AB - Disseminated superficial actinic porokeratosis (DSAP) is an inherited disorder of keratinization readily diagnosed through clinical and histologic examination. While generally benign in nature, the lesions can have profound psychosocial implications for patients. Although no cure exists, a number of treatment modalities, from topical medications to laser and light devices, have been reported with variable success. The authors report two cases of DSAP treated with the 1927-nm thulium fiber fractional laser along with a review of the treatment literature for DSAP. This therapy is convenient and safe with nearly no downtime or morbidity associated with pigment or textural changes. PMID- 26820043 TI - "Drug-Induced Liver Injury Clinical Consortia: a global research response for a worldwide health challenge". PMID- 26820044 TI - A National Population Study of the Co-Occurrence of Multiple Long-Term Conditions in People With Multimorbidity, Denmark, 2013. AB - The objective of this study was to describe the prevalence of pairwise combinations of 17 long-term conditions. Data were obtained from a national, representative population-based study including 162,283 Danish citizens aged 16 years or older. We calculated the prevalence of each long-term condition given the presence of another long-term condition. Compared with the general population, people with angina pectoris had more than twice the odds of having 12 of the 16 other long-term conditions, and inversely, people with cancer, tinnitus, or cataracts did not have notably higher odds for any of the other long term conditions. PMID- 26820045 TI - Return on Investment for Digital Behavioral Counseling in Patients With Prediabetes and Cardiovascular Disease. AB - INTRODUCTION: We calculated the health and economic impacts of participation in a digital behavioral counseling service that is designed to promote a healthful diet and physical activity for cardiovascular disease prevention in adults with prediabetes and cardiovascular disease risk factors (Prevent, Omada Health, San Francisco, California). This program enhances the Centers for Disease Control and Prevention's Diabetes Prevention Recognition Program. Participants completed a 16 week core program followed by an ongoing maintenance program. METHODS: Analysis was conducted for 2 populations meeting criteria for lifestyle intervention: 1) prediabetes (n = 1,663), and 2) high cardiovascular disease risk (n = 2,152). The Markov-based model simulated clinical and economic outcomes related to obesity and diabetes annually over 10 years for the 2 defined populations. Comparisons were made between participants and propensity-matched controls from the community. RESULTS: The return-on-investment break-even point was 3 years in both populations. Simulated return on investment for the population with prediabetes was $9 and $1,565 at years 3 and 5, respectively. Simulated return on investment for the population with cardiovascular disease risk was $96 and $1,512 at years 3 and 5, respectively. Results suggest that program participation reduces diabetes incidence by 30% to 33% and stroke by 11% to 16% over 5 years. CONCLUSION: Digital Behavioral Counseling provides significant health benefits to patients with prediabetes and cardiovascular disease and a positive return on investment. PMID- 26820046 TI - Recruitment in Clinical Versus Community-Based Sites for a Pilot Youth Diabetes Prevention Program, East Harlem, New York, 2011-2012. AB - INTRODUCTION: Little is known about successful strategies for recruitment of youth for research. The objective of this study was to compare clinical sites with community sites in the recruitment of teenagers for a new youth diabetes prevention program in East Harlem, New York. METHODS: We assessed diabetes risk for youth (aged 13-19 y) by measuring body mass index (BMI). We then screened overweight and obese youth for prediabetes using oral glucose tolerance testing, had them complete a health and lifestyle survey, and enrolled prediabetic youth into peer-led workshops. The recruitment strategies were 1) clinical referrals and 2) screenings at community sites. We compared the number of adolescents screened, the proportion eligible for testing, the proportion diagnosed with prediabetes, baseline characteristics, and the retention rates between those recruited in clinical and community sites. RESULTS: In 3 months, we completed BMI screening for 156 adolescents from community sites and 30 from clinical sites. Overall, 47% were at risk for diabetes on the basis of BMI, and 63% returned for diabetes testing; 35% had prediabetes, and 1 teenager had diabetes. Clinical sites yielded higher rates of diabetes risk on the basis of BMI and higher rates of return for screening and diagnosed prediabetes. Although demographics and BMI did not vary by recruitment site, we found differences in behaviors, self efficacy, body image, and social support. There were no differences by recruitment site in workshop enrollment or completion or return for follow-up. CONCLUSION: Both recruitment strategies were successful, and participants from both groups had high rates of undiagnosed prediabetes. Our approach allowed access to more adolescents and opportunities for education about diabetes in the community. PMID- 26820047 TI - Routine Check-Ups and Other Factors Affecting Discussions With a Health Care Provider About Subjective Memory Complaints, Behavioral Risk Factor Surveillance System, 21 States, 2011. AB - INTRODUCTION: Most adults reporting subjective memory complaints (SMCs) do not discuss them with a health care provider and miss an opportunity to learn about treatment options or receive a diagnosis. The objective of this study was to describe correlates of discussing memory problems with a health care professional among adults reporting SMCs. METHODS: Data were from 10,276 respondents aged 45 years or older in 21 states reporting SMCs on the 2011 Behavioral Risk Factor Surveillance System (BRFSS). Odds ratios (ORs) adjusted for demographic and health-related measures were computed for discussing SMCs with a health care professional. RESULTS: Among all respondents aged 45 or older reporting SMCs, 22.9% reported discussing them with a health care professional; among those reporting a recent routine check-up, this rate was 25.2%. The largest adjusted OR for discussing SMCs with a health care professional was for respondents reporting that SMCs always (vs never) caused them to give up household chores (OR, 3.02) or always (vs never) interfered with work (OR, 2.98). Increasing age reduced the likelihood of discussing SMCs. Among respondents who discussed SMCs, 41.8% received treatment. CONCLUSION: Routine check-ups may be a missed opportunity for discussions of SMCs that might lead to diagnosis or treatment. The Affordable Care Act requires a cognitive assessment for Medicare recipients during their annual wellness visit, but these results suggest that adults younger than 65 might also benefit from such an assessment. PMID- 26820048 TI - Biological standards of living: age at menarche vs height. AB - Background Researchers typically use height to understand the growth environment, but recent evidence suggests that height does not reflect it well; height can even be misleading. Aim This study compared age at menarche and height to assess which better reflected the growth environment. Subjects and methods This study employed the Indonesian Family Life Survey to extract information on age at menarche from 7831 women and height from 7946 men, both aged 15-49 and born in 1944-1983. It drew on GDP per capita in childhood to represent the growth environment. The means of the two anthropometrics by birth decade were calculated. The trends in the two were then compared and each was regressed on the growth environment and a time trend. Results Between 1944-1953 and 1974-1983, the mean age at menarche decreased from 14.5 to 13.9, while height increased from 160.9 cm to 162.6 cm. Despite the expected broad trends, age at menarche was more closely related to the growth environment than height in graphs, correlation coefficients and regression results. Conclusion The results recommend using more than one anthropometric to investigate changes in the biological standards of living. PMID- 26820049 TI - Facile and Sensitive Fluorescence Sensing of Alkaline Phosphatase Activity with Photoluminescent Carbon Dots Based on Inner Filter Effect. AB - A simple and sensitive fluorescent assay for detecting alkaline phosphatase (ALP) based on the inner filter effect (IFE) has been proven, which is conceptually different from the previously reported ALP fluorescent assays. In this sensing platform, N-doped carbon dots (CDs) with a high quantum yield of 49% were prepared by one-pot synthesis and were directly used as a fluorophore in IFE. p Nitrophenylphosphate (PNPP) was employed to act as an ALP substrate, and its enzyme catalytic product (p-nitrophenol (PNP)) was capable of functioning as a powerful absorber in IFE to influence the excitation of fluorophore (CDs). When in the presence of ALP, PNPP was transformed into PNP and induced the absorption band transition from 310 to 405 nm, which resulted in the complementary overlap between the absorption of PNP and the excitation of CDs. Because of the competitive absorption, the excitation of CDs was significantly weakened, resulting in the quenching of CDs. The present IFE-based sensing strategy showed a good linear relationship from 0.01 to 25 U/L (R(2) = 0.996) and provided an exciting detection limit of 0.001 U/L (signal-to-noise ratio of 3). The proposed sensing approach was successfully applied to ALP sensing in serum samples, ALP inhibitor investigation and phosphatase cell imaging. The presented IFE-based CDs fluorescence sensing strategy gives new insight on the development of the facile and sensitive optical probe for enzyme activity assay because the surface modification or the linking between the receptor and the fluorophore is no longer required. PMID- 26820050 TI - Higher urine heat shock protein 70/creatinine ratio in type 1 diabetes mellitus. AB - Insidious progressive renal damage caused by type 1 diabetes mellitus (T1DM) begins in childhood before it becomes manifest in adult ages. Heat shock proteins (HSPs) regulate the cell response to any hazardous factors to prevent cell structure. The aim of the study is to determine whether urine levels of HSPs increase in diabetic children with time and indicate a progressive renal injury in T1DM. Thirty-three patients with T1DM and 24 healthy children were enrolled in the study. Renal function was normal in all patients. Urine levels of HSP27, HSP40, HSP60, HSP70, and HSP90 were measured by enzyme-linked immunosorbent assay at two consecutive years (2012 and 2013). The results were evaluated as urine HSP/creatinine ratios (uHSP/Cr). Mean urine HSP27/Cr, HSP40/Cr, HSP60/Cr, HSP70/Cr, HSP90/Cr in patient group were significantly higher than in controls in 2012 (uHSP27/Cr 460.12 +/- 217.64 versus 270.02 +/- 136.83 pg/mgCr; uHSP40/Cr 180.89 +/- 118.59 versus 99.44 +/- 62.49 pg/mgCr; uHSP60/Cr 114.40 +/- 64.91 versus 70.50 +/- 43.70 pg/mgCr; uHSP70/Cr 41.17 +/- 28.42 versus 16.47 +/- 7.32 pg/mgCr; uHSP90/Cr 175.64 +/- 102.22 versus 107.61 +/- 75.85 pg/mgCr) (p < 0.05). In 2013, uHSP70/Cr level increased significantly (51.08 +/- 27.72 pg/mgCr; p = 0.001), whereas uHSP60/Cr level decreased and uHSP27/Cr, uHSP40/Cr, uHSP90/Cr levels remained stable (p > 0.05). Area under the curve (AUC) for uHSP70/Cr (0.957) was significantly higher than the others. Using a cutoff 22.59 pg/mgCr for uHSP70/Cr to predict of diabetic damage, sensitivity and specificity were 85% and 96%, respectively. Our results suggest that uHSP70/Cr increases over time and may indicate early phases of progressive kidney damage in diabetic children. PMID- 26820051 TI - Modeling the effect of pathogenic mutations on the conformational landscape of protein kinases. AB - Most proteins assume different conformations to perform their cellular functions. This conformational dynamics is physiologically regulated by binding events and post-translational modifications, but can also be affected by pathogenic mutations. Atomistic molecular dynamics simulations complemented by enhanced sampling approaches are increasingly used to probe the effect of mutations on the conformational dynamics and on the underlying conformational free energy landscape of proteins. In this short review we discuss recent successful examples of simulations used to understand the molecular mechanism underlying the deregulation of physiological conformational dynamics due to non-synonymous single point mutations. Our examples are mostly drawn from the protein kinase family. PMID- 26820052 TI - Bone Morphogenetic Protein-6 Mutations Take Their Place in Iron Overload Diseases. PMID- 26820053 TI - Magnetic Resonance Imaging/Elastography Is Superior to Transient Elastography for Detection of Liver Fibrosis and Fat in Nonalcoholic Fatty Liver Disease. PMID- 26820054 TI - Aligning Quality With the Academic Mission: A Quality Improvement and Delivery Science Program in Gastroenterology. PMID- 26820055 TI - Development of an audit toolkit for use in resource-poor countries. PMID- 26820056 TI - Active Monitoring of Travelers Arriving from Ebola-Affected Countries - New York City, October 2014-April 2015. AB - The Ebola virus disease (Ebola) outbreak in West Africa has claimed approximately 11,300 lives (1), and the magnitude and course of the epidemic prompted many nonaffected countries to prepare for Ebola cases imported from affected countries. In October 2014, CDC and the Department of Homeland Security (DHS) implemented enhanced entry risk assessment and management at five U.S. airports: John F. Kennedy (JFK) International Airport in New York City (NYC), O'Hare International Airport in Chicago, Newark Liberty International Airport in New Jersey, Hartsfield-Jackson International Airport in Atlanta, and Dulles International Airport in Virginia (2). Enhanced entry risk assessment began at JFK on October 11, 2014, and at the remaining airports on October 16 (3). On October 21, DHS exercised its authority to direct all travelers flying into the United States from an Ebola-affected country to arrive at one of the five participating airports. At the time, the Ebola-affected countries included Guinea, Liberia, Mali, and Sierra Leone. On October 27, CDC issued updated guidance for monitoring persons with potential Ebola virus exposure (4), including recommending daily monitoring of such persons to ascertain the presence of fever or symptoms for a period of 21 days (the maximum incubation period of Ebola virus) after the last potential exposure; this was termed "active monitoring." CDC also recommended "direct active monitoring" of persons with a higher risk for Ebola virus exposure, including health care workers who had provided direct patient care in Ebola-affected countries. Direct active monitoring required direct observation of the person being monitored by the local health authority at least once daily (5). This report describes the operational structure of the NYC Department of Health and Mental Hygiene's (DOHMH) active monitoring program during its first 6 months (October 2014-April 2015) of operation. Data collected on persons who required direct active monitoring are not included in this report. PMID- 26820058 TI - Benzyl butyl phthalate promotes adipogenesis in 3T3-L1 preadipocytes: A High Content Cellomics and metabolomic analysis. AB - Benzyl butyl phthalate (BBP) has been known to induce developmental and reproductive toxicity. However, its association with dysregulation of adipogenesis has been poorly investigated. The present study aimed to examine the effect of BBP on the adipogenesis, and to elucidate the underlying mechanisms using the 3T3-L1 cells. The capacity of BBP to promote adipogenesis was evaluated by multiple staining approaches combined with a High Content Cellomics analysis. The dynamic changes of adipogenic regulatory genes and proteins were examined, and the metabolite profile was identified using GC/MC based metabolomic analysis. The High Content analysis showed BBP in contrast with Bisphenol A (BPA), a known environmental obesogen, increased lipid droplet accumulation in a similar dose dependent manner. However, the size of the lipid droplets in BBP-treated cells was significantly larger than those in cells treated with BPA. BBP significantly induced mRNA expression of transcriptional factors C/EBPalpha and PPARgamma, their downstream genes, and numerous adipogenic proteins in a dose and time dependent manner. Furthermore, GC/MC metabolomic analysis revealed that BBP exposure perturbed the metabolic profiles that are associated with glyceroneogenesis and fatty acid synthesis. Altogether, our current study clearly demonstrates that BBP promoted the differentiation of 3T3-L1 through the activation of the adipogenic pathway and metabolic disturbance. PMID- 26820057 TI - Identification of compounds that modulate retinol signaling using a cell-based qHTS assay. AB - In vertebrates, the retinol (vitamin A) signaling pathway (RSP) controls the biosynthesis and catabolism of all-trans retinoic acid (atRA), which regulates transcription of genes essential for embryonic development. Chemicals that interfere with the RSP to cause abnormal intracellular levels of atRA are potential developmental toxicants. To assess chemicals for the ability to interfere with retinol signaling, we have developed a cell-based RARE (Retinoic Acid Response Element) reporter gene assay to identify RSP disruptors. To validate this assay in a quantitative high-throughput screening (qHTS) platform, we screened the Library of Pharmacologically Active Compounds (LOPAC) in both agonist and antagonist modes. The screens detected known RSP agonists, demonstrating assay reliability, and also identified novel RSP agonists including kenpaullone, niclosamide, PD98059 and SU4312, and RSP antagonists including Bay 11-7085, LY294002, 3,4-Methylenedioxy-beta-nitrostyrene, and topoisomerase inhibitors (camptothecin, topotecan, amsacrine hydrochloride, and idarubicin). When evaluated in the P19 pluripotent cell, these compounds were found to affect the expression of the Hoxa1 gene that is essential for embryo body patterning. These results show that the RARE assay is an effective qHTS approach for screening large compound libraries to identify chemicals that have the potential to adversely affect embryonic development through interference with retinol signaling. PMID- 26820059 TI - Relapse prevention medications in community treatment for young adults with opioid addiction. AB - BACKGROUND: Despite the well-known effectiveness and widespread use of relapse prevention medications such as extended release naltrexone (XR-NTX) and buprenorphine for opioid addiction in adults, less is known about their use in younger populations. METHODS: This was a naturalistic study using retrospective chart review of N = 56 serial admissions into a specialty community treatment program that featured the use of relapse prevention medications for young adults (19-26 years old) with opioid use disorders. Treatment outcomes over 24 weeks included retention and weekly opioid-negative urine tests. RESULTS: Patients were of mean age 23.1, 70% male, 86% Caucasian, 82% with history of injection heroin use, and treated with either buprenorphine (77%) or XR-NTX (23%). The mean number of XR-NTX doses received was 4.1. Retention was approximately 65% at 12 weeks and 40% at 24 weeks, and rates of opioid-negative urine were 50% at 12 weeks and 39% at 24 weeks, with missing samples imputed as positive. There were no statistically significant differences in retention (t = 1.87, P = .06) or in rates of weekly opioid-negative urine tests (t = 1.96, P = .06) between medication groups, over the course of 24 weeks. The XR-NTX group had higher rates of weekly negative urine drug tests for other nonopioid substances (t = 2.83, P < .05) compared with the buprenorphine group. Males were retained in treatment longer and had higher rates of opioid-negative weeks compared with females. CONCLUSIONS: These results suggest that relapse prevention medications including both buprenorphine and XR-NTX can be effectively incorporated into standard community treatment for opioid addiction in young adults with good results. Specialty programming focused on opioid addiction in young adults may provide a promising model for further treatment development. PMID- 26820060 TI - Mechanical robustness of the calcareous tubeworm Hydroides elegans: warming mitigates the adverse effects of ocean acidification. AB - Development of antifouling strategies requires knowledge of how fouling organisms would respond to climate change associated environmental stressors. Here, a calcareous tube built by the tubeworm, Hydroides elegans, was used as an example to evaluate the individual and interactive effects of ocean acidification (OA), warming and reduced salinity on the mechanical properties of a tube. Tubeworms produce a mechanically weaker tube with less resistance to simulated predator attack under OA (pH 7.8). Warming (29 degrees C) increased tube volume, tube mineral density and the tube's resistance to a simulated predatory attack. A weakening effect by OA did not make the removal of tubeworms easier except for the earliest stage, in which warming had the least effect. Reduced salinity (27 psu) did not affect tubes. This study showed that both mechanical analysis and computational modeling can be integrated with biofouling research to provide insights into how fouling communities might develop in future ocean conditions. PMID- 26820061 TI - Stability and change in risk-taking propensity across the adult life span. AB - Can risk-taking propensity be thought of as a trait that captures individual differences across domains, measures, and time? Studying stability in risk-taking propensities across the life span can help to answer such questions by uncovering parallel, or divergent, trajectories across domains and measures. We contribute to this effort by using data from respondents aged 18 to 85 in the German Socio Economic Panel Study (SOEP) and by examining (a) differential stability, (b) mean level differences, and (c) individual-level changes in self-reported general (N = 44,076) and domain-specific (N = 11,903) risk-taking propensities across adulthood. In addition, we investigate (d) the correspondence between cross sectional trajectories of self-report and behavioral measures of social (trust game; N = 646) and nonsocial (monetary gamble; N = 433) risk taking. The results suggest that risk-taking propensity can be understood as a trait with moderate stability. Results show reliable mean-level differences across the life span, with risk-taking propensities typically decreasing with age, although significant variation emerges across domains and individuals. Interestingly, the mean-level trajectory for behavioral measures of social and nonsocial risk taking was similar to those obtained from self-reported risk, despite small correlations between task behavior and self-reports. Individual-level analyses suggest a link between changes in risk-taking propensities both across domains and in relation to changes in some of the Big Five personality traits. Overall, these results raise important questions concerning the role of common processes or events that shape the life span development of risk-taking across domains as well as other major personality facets. (PsycINFO Database Record PMID- 26820062 TI - Recombinant plasmid-based quantitative Real-Time PCR analysis of Salmonella enterica serotypes and its application to milk samples. AB - The aim of the current study was to develop, a new, rapid, sensitive and quantitative Salmonella detection method using a Real-Time PCR technique based on an inexpensive, easy to produce, convenient and standardized recombinant plasmid positive control. To achieve this, two recombinant plasmids were constructed as reference molecules by cloning the two most commonly used Salmonella-specific target gene regions, invA and ttrRSBC. The more rapid detection enabled by the developed method (21 h) compared to the traditional culture method (90 h) allows the quantitative evaluation of Salmonella (quantification limits of 10(1)CFU/ml and 10(0)CFU/ml for the invA target and the ttrRSBC target, respectively), as illustrated using milk samples. Three advantages illustrated by the current study demonstrate the potential of the newly developed method to be used in routine analyses in the medical, veterinary, food and water/environmental sectors: I--The method provides fast analyses including the simultaneous detection and determination of correct pathogen counts; II--The method is applicable to challenging samples, such as milk; III--The method's positive controls (recombinant plasmids) are reproducible in large quantities without the need to construct new calibration curves. PMID- 26820063 TI - Adopting genetics: motivations and outcomes of personal genomic testing in adult adoptees. AB - PURPOSE: American adult adoptees may possess limited information about their biological families and turn to direct-to-consumer personal genomic testing (PGT) for genealogical and medical information. We investigated the motivations and outcomes of adoptees undergoing PGT using data from the Impact of Personal Genomics (PGen) Study. METHODS: The PGen Study surveyed new 23andMe and Pathway Genomics customers before and 6 months after receiving PGT results. Exploratory analyses compared adoptees' and nonadoptees' PGT attitudes, expectations, and experiences. We evaluated the association of adoption status with motivations for testing and postdisclosure actions using logistic regression models. RESULTS: Of 1,607 participants, 80 (5%) were adopted. As compared with nonadoptees, adoptees were more likely to cite limited knowledge of family health history (OR = 10.1; 95% CI = 5.7-19.5) and the opportunity to learn genetic disease risks (OR = 2.7; 95% CI = 1.6-4.8) as strong motivations for PGT. Of 922 participants who completed 6-month follow-up, there was no significant association between adoption status and PGT-motivated health-care utilization or health-behavior change. CONCLUSION: PGT allows adoptees to gain otherwise inaccessible information about their genetic disease risks and ancestry, helping them to fill the void of an incomplete family health history.Genet Med 18 9, 924-932. PMID- 26820064 TI - Cardiovascular malformations caused by NOTCH1 mutations do not keep left: data on 428 probands with left-sided CHD and their families. AB - PURPOSE: We aimed to determine the prevalence and phenotypic spectrum of NOTCH1 mutations in left-sided congenital heart disease (LS-CHD). LS-CHD includes aortic valve stenosis, a bicuspid aortic valve, coarctation of the aorta, and hypoplastic left heart syndrome. METHODS: NOTCH1 was screened for mutations in 428 nonsyndromic probands with LS-CHD, and family histories were obtained for all. When a mutation was detected, relatives were also tested. RESULTS: In 148/428 patients (35%), LS-CHD was familial. Fourteen mutations (3%; 5 RNA splicing mutations, 8 truncating mutations, 1 whole-gene deletion) were detected, 11 in familial disease (11/148 (7%)) and 3 in sporadic disease (3/280 (1%)). Forty-nine additional mutation carriers were identified among the 14 families, of whom 12 (25%) were asymptomatic. Most of these mutation carriers had LS-CHD, but 9 (18%) had right-sided congenital heart disease (RS-CHD) or conotruncal heart disease (CTD). Thoracic aortic aneurysms (TAAs) occurred in 6 mutation carriers (probands included 6/63 (10%)). CONCLUSION: Pathogenic mutations in NOTCH1 were identified in 7% of familial LS-CHD and in 1% of sporadic LS-CHD. The penetrance is high; a cardiovascular malformation was found in 75% of NOTCH1 mutation carriers. The phenotypic spectrum includes LS-CHD, RS-CHD, CTD, and TAA. Testing NOTCH1 for an early diagnosis in LS-CHD/RS-CHD/CTD/TAA is warranted.Genet Med 18 9, 914-923. PMID- 26820065 TI - Evidence for an association between infant mortality and homozygosity for the arctic variant of carnitine palmitoyltransferase 1A. AB - PURPOSE: Infant mortality in Alaska is highest among Alaska Native people from western/northern Alaska, a population with a high prevalence of a genetic variant (c.1436C>T; the arctic variant) of carnitine palmitoyltransferase 1A (CPT1A). METHODS: We performed an unmatched case-control study to determine the relationship between the arctic variant and infant mortality. The cases were 110 Alaska Native infant deaths from 2006 to 2010 and the controls were 395 Alaska Native births from the same time period. In addition to the overall analysis, we conducted two subanalyses, one limited to subjects from western/northern Alaska and one limited to infants heterozygous or homozygous for the arctic variant. RESULTS: Among western/northern Alaska residents, 66% of cases and 61% of controls were homozygous (adjusted odds ratio (aOR): 2.5; 95% confidence interval (CI): 1.3, 5.0). Among homozygous or heterozygous infants, 58% of cases and 44% of controls were homozygous (aOR: 2.3; 95% CI: 1.3, 4.0). Deaths associated with infection were more likely to be homozygous (OR: 2.9; 95% CI: 1.0-8.0). Homozygosity was strongly associated with a premorbid history of pneumonia, sepsis, or meningitis. CONCLUSION: Homozygosity for the arctic variant is associated with increased risk of infant mortality, which may be mediated in part by an increase in infectious disease risk. Further studies are needed to determine whether the association we report represents a causal association between the CPT1A arctic variant and infectious disease-specific mortality.Genet Med 18 9, 933-939. PMID- 26820066 TI - Hypomorphic mutations identified in the candidate Leber congenital amaurosis gene CLUAP1. AB - PURPOSE: Leber congenital amaurosis (LCA) is an early-onset form of retinal degeneration. Six of the 22 known LCA genes encode photoreceptor ciliary proteins. Despite the identification of 22 LCA genes, the genetic basis of ~30% of LCA patients remains unknown. We sought to investigate the cause of disease in the remaining 30% by examining cilia-associated genes. METHODS: Whole-exome sequencing was performed on an LCA cohort of 212 unsolved probands previously screened for mutations in known retinal-disease genes. Immunohistochemistry using mouse retinas was used to confirm protein localization and zebrafish were used to perform rescue experiments. RESULTS: A homozygous nonsynonymous mutation was found in a single proband in CLUAP1, a gene required for ciliogenesis and cilia maintenance. Cluap1 knockout zebrafish exhibit photoreceptor cell death as early as 5 days after fertilization, and rescue experiments revealed that our proband's mutation is significantly hypomorphic. CONCLUSION: Consistent with the knowledge that CLUAP1 plays an important role in cilia function and that cilia are critical to photoreceptor function, our results indicate that hypomorphic mutations in CLUAP1 can result in dysfunctional photoreceptors without systemic abnormalities. This is the first report linking mutations in CLUAP1 to human disease and establishes CLUAP1 as a candidate LCA gene.Genet Med 18 10, 1044-1051. PMID- 26820067 TI - Predictive genetic testing of minors: evidence and experience with families. PMID- 26820069 TI - A-769662, a direct AMPK activator, attenuates lipopolysaccharide-induced acute heart and lung inflammation in rats. AB - Activation of AMP-activated protein kinase (AMPK) has been indicated to produce an anti-inflammatory effect through the suppression of toll-like receptor (TLR) activity. In the present study, the investigation was designed to identify the effect of A-769662, a direct activator of AMPK on lipopolysaccharide (LPS) induced acute lung and heart inflammation in rats. To induce inflammation, an intraperitoneal injection of LPS (0.5 mg/kg) was administered to Wistar rats. The inflammatory parameters and AMPK phosphorylation were then measured 9 h later. For the treatment group, A-769662 (10 mg/kg) was administrated intraperitoneally immediately prior to LPS injection. The results demonstrated that A-769662 attenuated the LPS-induced acute inflammation in the heart and lung tissue, as indicated by the significant reduction in myeloperoxidase activity (P<0.001) and inhibition of tissue damage. This was associated with a significant reduction in tumor necrosis factor-alpha serum levels (P<0.01) and peripheral neutrophils (P<0.001). Furthermore, A-769662 enhanced AMPK phosphorylation and downregulated the expression of MyD88, a TLR adaptor protein, in the heart tissue. Despite the anti-inflammatory effect of A-769662 on LPS-induced inflammation in the lung tissue, the drug produced no effect on the MyD88 expression levels or AMPK phosphorylation in the tissue. The results of the present study suggested that the administration of A-769662 results in an anti-inflammatory effect in the LPS induced model of inflammation in rats. The anti-inflammatory activity was demonstrated in the heart and lung tissues and the effect on the cardiac tissue was indicated to be a result of AMPK activation, involving the suppression of TLRs. PMID- 26820068 TI - Low-pass whole-genome sequencing in clinical cytogenetics: a validated approach. AB - PURPOSE: Chromosomal microarray analysis is the gold standard for copy-number variant (CNV) detection in prenatal and postnatal diagnosis. We aimed to determine whether next-generation sequencing (NGS) technology could be an alternative method for CNV detection in routine clinical application. METHODS: Genome-wide CNV analysis (>50 kb) was performed on a multicenter group of 570 patients using a low-coverage whole-genome sequencing pipeline. These samples were referred for chromosomal analysis; CNVs (i.e., pathogenic CNVs, pCNVs) were classified according to the American College of Medical Genetics and Genomics guidelines. RESULTS: Overall, a total of 198 abortuses, 37 stillbirths, 149 prenatal, and 186 postnatal samples were tested. Our approach yielded results in 549 samples (96.3%). In addition to 119 subjects with aneuploidies, 103 pCNVs (74 losses and 29 gains) were identified in 82 samples, giving diagnostic yields of 53.2% (95% confidence interval: 45.8, 60.5), 14.7% (5.0, 31.1), 28.5% (21.1, 36.6), and 30.1% (23.6, 37.3) in each group, respectively. Mosaicism was observed at a level as low as 25%. CONCLUSIONS: Patients with chromosomal diseases or microdeletion/microduplication syndromes were diagnosed using a high-resolution genome-wide method. Our study revealed the potential of NGS to facilitate genetic diagnoses that were not evident in the prenatal and postnatal groups.Genet Med 18 9, 940-948. PMID- 26820070 TI - A rare case of ankylosing spondylitis combined with incomplete paralysis. PMID- 26820071 TI - Intramuscular nodular fasciitis of the erector spinae muscle mimicking soft tissue sarcoma. PMID- 26820072 TI - Thrombosis of the inferior vena cava presenting with findings of radiculopathy. PMID- 26820073 TI - Spinal epidural abscess as a complication of Crohn's disease. PMID- 26820074 TI - Dual-Targeting Lactoferrin-Conjugated Polymerized Magnetic Polydiacetylene Assembled Nanocarriers with Self-Responsive Fluorescence/Magnetic Resonance Imaging for In Vivo Brain Tumor Therapy. AB - Maintaining a high concentration of therapeutic agents in the brain is difficult due to the restrictions of the blood-brain barrier (BBB) and rapid removal from blood circulation. To enable controlled drug release and enhance the blood-brain barrier (BBB)-crossing efficiency for brain tumor therapy, a new dual-targeting magnetic polydiacetylene nanocarriers (PDNCs) delivery system modified with lactoferrin (Lf) is developed. The PDNCs are synthesized using the ultraviolet (UV) cross-linkable 10,12-pentacosadiynoic acid (PCDA) monomers through spontaneous assembling onto the surface of superparamagnetic iron oxide (SPIO) nanoparticles to form micelles-polymerized structures. The results demonstrate that PDNCs will reduce the drug leakage and further control the drug release, and display self-responsive fluorescence upon intracellular uptake for cell trafficking and imaging-guided tumor treatment. The magnetic Lf-modified PDNCs with magnetic resonance imaging (MRI) and dual-targeting ability can enhance the transportation of the PDNCs across the BBB for tracking and targeting gliomas. An enhanced therapeutic efficiency can be obtained using Lf-Cur (Curcumin)-PDNCs by improving the retention time of the encapsulated Cur and producing fourfold higher Cur amounts in the brain compared to free Cur. Animal studies also confirm that Lf targeting and controlled release act synergistically to significantly suppress tumors in orthotopic brain-bearing rats. PMID- 26820075 TI - The effect of NFATc1 on vascular generation and the possible underlying mechanism in epithelial ovarian carcinoma. AB - We investigated the effect of nuclear factor of activated T cells c1 (NFATc1) on the growth and vascular generation of human ovarian carcinoma SKOV3 cell transplanted tumors in nude mice and explored the possible underlying mechanism. NFATc1 siRNA was transfected into the SKOV3 cells, which were then subjected to immunofluorescence tests and real-time reverse transcription polymerase chain reaction (RT-PCR) to determine the transfection-induced inhibition rate. The tumor volumes in the nude mice in all groups were measured to determine the in vivo antitumor effect of NFATc1 siRNA. Immunohistochemical (IHC) methods were employed to detect NFATc1 expression in tumor tissue, combined with cytokeratin (CK) staining to label the epithelial origin of the tumor tissue. CD34 and podoplanin were used as markers for labeling microvessels and microlymphatic vessels, respectively. The densities of microvessels and microlymphatic vessels in each group were calculated and statistically analyzed. RT-PCR and western blotting were performed to detect the protein and mRNA expression levels of NFATc1, the ELR+ CXC chemokine interleukin (IL)-8, fibroblast growth factor-2 (FGF-2), and platelet-derived growth factor BB (PDGF BB) in xenografted tumor tissue in all groups. NFATc1 was highly expressed in tumor tissue in the control groups. The intervention group exhibited a tumor growth inhibition rate of 57.08% and presented a lower tumor weight and volume compared with the two control groups. In the control groups, the microvessel densities were 12.00 +/- 1.65 and 11.47 +/- 0.32, respectively, and the microlymphatic vessel densities were 10.03 +/- 0.96 and 9.95 +/- 1.12; these values were significantly higher than in the intervention group. RT-PCR and western blot shows that NFATc1 siRNA could markedly suppress the expression of IL-8, FGF-2 and PDGF BB at the mRNA and the protein level. In conclusion, it was shown that NFATc1 siRNA significantly suppresses the growth and vascular generation of SKOV3 human ovarian carcinoma cell-transplanted tumors subcutaneously xenografted into nude mice. The downregulation of the expression of IL-8, FGF-2 and PDGF BB may be one of the mechanisms underlying the above inhibitory effects. PMID- 26820076 TI - Chronic sciatic nerve compression induces fibrosis in dorsal root ganglia. AB - In the present study, pathological alterations in neurons of the dorsal root ganglia (DRG) were investigated in a rat model of chronic sciatic nerve compression. The rat model of chronic sciatic nerve compression was established by placing a 1 cm Silastic tube around the right sciatic nerve. Histological examination was performed via Masson's trichrome staining. DRG injury was assessed using Fluoro Ruby (FR) or Fluoro Gold (FG). The expression levels of target genes were examined using reverse transcription-quantitative polymerase chain reaction, western blot and immunohistochemical analyses. At 3 weeks post compression, collagen fiber accumulation was observed in the ipsilateral area and, at 8 weeks, excessive collagen formation with muscle atrophy was observed. The collagen volume fraction gradually and significantly increased following sciatic nerve compression. In the model rats, the numbers of FR-labeled DRG neurons were significantly higher, relative to the sham-operated group, however, the numbers of FG-labeled neurons were similar. In the ipsilateral DRG neurons of the model group, the levels of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) were elevated and, surrounding the neurons, the levels of collagen type I were increased, compared with those in the contralateral DRG. In the ipsilateral DRG, chronic nerve compression was associated with significantly higher levels of phosphorylated (p)-extracellular signal-regulated kinase 1/2, and significantly lower levels of p-c-Jun N-terminal kinase and p-p38, compared with those in the contralateral DRGs. Chronic sciatic nerve compression likely induced DRG pathology by upregulating the expression levels of TGF-beta1, CTGF and collagen type I, with involvement of the mitogen activated protein kinase signaling pathway. PMID- 26820077 TI - Can endosheath technology open primary care doors to Barrett's esophagus screening by transnasal endoscopy? PMID- 26820078 TI - Will endoscopic ultrasound-guided bile duct drainage replace ERCP? PMID- 26820079 TI - Endoscopic band ligation for gastric antral vascular ectasia: time for a new indication? PMID- 26820080 TI - Split-dose low-volume bowel preparation, a feasible option for preparation for colonoscopy. PMID- 26820081 TI - Reply to Azmi et al. PMID- 26820082 TI - Is the ESGE guideline recommendation against the placement of stents for left sided malignant colonic obstruction still open to debate? PMID- 26820083 TI - Reply to Kim. PMID- 26820086 TI - [French comment on article: Comparison of the histopathological effects of two electrosurgical currents in an in vivo porcine model of esophageal endoscopic mucosal resection]. PMID- 26820087 TI - [French comment on article: In-class didactic versus self-directed teaching of the probe-based confocal laser endomicroscopy (pCLE) criteria for Barrett's esophagus]. PMID- 26820088 TI - [French comment on article: Utility of clinical suspicion and endoscopic re examination for detection of esophagogastric perforation after pneumatic dilation for achalasia]. PMID- 26820089 TI - [French comment on article: Repeat peroral endoscopic myotomy: a salvage option for persistent/recurrent symptoms]. PMID- 26820090 TI - [French comment on article: Clinical outcomes following stent placement in refractory benign esophageal stricture: a systematic review and meta-analysis]. PMID- 26820091 TI - [French comment on article: Comparison of the clinical impact of endoscopic ultrasound-guided choledochoduodenostomy and hepaticogastrostomy for bile duct obstruction with duodenal obstruction]. PMID- 26820092 TI - [French comment on article: Management of the complications of submucosal tunneling endoscopic resection for upper gastrointestinal submucosal tumors]. PMID- 26820093 TI - [French comment on article: Endoscopic ultrasound-guided choledochoduodenostomy vs. transpapillary stenting for distal biliary obstruction]. PMID- 26820094 TI - Video Comment on Bishnu P. Joshi et al. PMID- 26820095 TI - Video Comment on Farzan F. Bahin et al. PMID- 26820096 TI - Adventitial ablation technique that permits the assessment of adventitial dependent contribution to microvascular contractile function. AB - Resistance arteries have been implicated as a major contributing factor in the sequela of disease conditions such as hypertension and diabetes and, as such, are a major focus of cardiovascular research. The paracrine influence of the intimal endothelial layer of resistance arteries is well established. Considering the growing body of evidence substantiating a functionally relevant vascular adventitia, in this study we have established a technique that permits determination of the functional influence of the adventitial layer on resistance artery tone. Isolating adventitial-dependent function, analogous to isolating endothelial function, has potentially significant implications for studying the as yet unexplored role of the microvascular adventitial layer in modulating acute vascular contractile function. PMID- 26820097 TI - Colorimetric detection of bisphenol A based on unmodified aptamer and cationic polymer aggregated gold nanoparticles. AB - In this study, a colorimetric method was exploited to detect bisphenol A (BPA) based on BPA-specific aptamer and cationic polymer-induced aggregation of gold nanoparticles (AuNPs). The principle of this assay is very classical. The aggregation of AuNPs was induced by the concentration of cationic polymer, which is controlled by specific recognition of aptamer with BPA and the reaction of aptamer and cationic polymer forming "duplex" structure. This method enables colorimetric detection of BPA with selectivity and a detection limit of 1.50 nM. In addition, this colorimetric method was successfully used to determine spiked BPA in tap water and river water samples. PMID- 26820098 TI - Cutaneous collagenous vasculopathy: Report of first Japanese case and review of the literature. AB - Cutaneous collagenous vasculopathy (CCV) is a rare acquired idiopathic microangiopathy characterised by the progressive development of diffuse asymptomatic telangiectasias over the skin. Histologically, the presence of a thick hyaline collagenous wall around the affected capillaries, comprising the accumulation of collagen type IV, is noted. We herein report the case of a 17 year-old Japanese boy with symmetrical patches of diffuse telangiectasias on the bilateral extremities that persisted for 10 months. A histological examination revealed dilated capillaries in the papillary dermis surrounded by thick perivascular deposition of hyaline-like materials, which stained positive for periodic acid-Schiff and collagen type IV. We additionally performed a review of 26 CCV patients previously reported in the English literature and summarised the clinical and histological features of generalised telangiectatic disorders, such as CCV, generalised essential telangiectasia and hereditary haemorrhagic telangiectasia. To establish an accurate diagnosis, it is important for dermatologists to recognise the clinical and histological characteristics of CCV and the importance of the histological analysis. PMID- 26820099 TI - Partially Fluorinated Graphene: Structural and Electrical Characterization. AB - Despite the number of existing studies that showcase the promising application of fluorinated graphene in nanoelectronics, the impact of the fluorine bonding nature on the relevant electrical behaviors of graphene devices, especially at low fluorine content, remains to be experimentally explored. Using CF4 as the fluorinating agent, we studied the gradual structural evolution of chemical vapor deposition graphene fluorinated by CF4 plasma at a working pressure of 700 mTorr using Raman and X-ray photoelectron spectroscopy (XPS). After 10 s of fluorination, our XPS analysis revealed a co-presence of covalently and ionically bonded fluorine components; the latter has been determined being a dominant contribution to the observation of two Dirac points in the relevant electrical measurement using graphene field effect transistor devices. Additionally, this ionic C-F component (ionic bonding characteristic charge sharing) is found to be present only at low fluorine content; continuous fluorination led to a complete transition to a covalently bonded C-F structure and a dramatic increase of graphene sheet resistance. Owing to the formation of these various C-F bonding components, our temperature-dependent Raman mapping studies show an inhomogeneous defluorination from annealing temperatures starting at ~150 degrees C for low fluorine coverage, whereas fully fluorinated graphene is thermally stable up to ~300 degrees C. PMID- 26820100 TI - Short-Term Resistance Training Attenuates Cardiac Autonomic Dysfunction in Obese Adolescents. AB - PURPOSE: Cardiac autonomic dysfunction (CADysf) in children is often associated to obesity and may be attenuated by physical activity. In this study, we investigated the effects of resistance training (RT) upon CADysf assessed by heart rate variability (HRV) in obese adolescents. METHOD: Volunteers were assigned into groups according to standard deviation scores for body mass index (z-BMI) and percentile for age and sex: obese (OB; z-BMI from 2 to 3 and >= 95th percentile, n = 24) and normal weight controls (CG; z-BMI from -2-1 and < 85th percentile, n = 20). OB performed isolated RT during 12 weeks [3 sets of 6-10reps with 70-85% 10RM]. Waist circumference, systolic/diastolic blood pressures (SBP/DBP), lipids, and HRV were assessed at baseline. Only OB underwent postintervention assessments. RESULTS: At baseline, SBP (122.4 +/- 9.1 vs. 109.7 +/- 11.5 mmHg, p < .001) and DBP (76.1 +/- 7.1 vs. 65.3 +/- 5.9 mmHg, p < .001) were higher, while parasympathetic HRV indexes were lower (p < .05) in OB compared with CG. After RT, waist circumference (3%, p < .001) and SBP (10%, p < .001) reduced in OB. Parasympathetic indexes of HRV increased in OB (SDNN: 25%, p = .03; rMSSD: 48%, p = .0006; pNN50: 67%, p = .001; total power: 54%, p = .01; HF: 101%, p = .001) and baseline differences between groups for sympathetic and parasympathetic activities were no longer observed after RT. CONCLUSION: RT attenuated CAdyfs and BP in obese adolescents, by increasing parasympathetic activity and decreasing sympatho-vagal balance. PMID- 26820101 TI - Endoscopic prediction of recurrence in patients with early gastric cancer after margin-negative endoscopic resection. AB - BACKGROUND AND AIM: Although follow-up endoscopy is routinely performed after endoscopic resection (ER) for early gastric cancer (EGC), it remains unclear whether resection scar biopsies should also be taken. This study sought to predict local recurrence at the ER scar on the basis of endoscopic criteria after margin-negative EGC resection and to determine the necessity of taking scar biopsies. METHODS: All consecutive patients with EGC who underwent margin negative ER in June 1995 to December 2011 and developed recurrence at the scar were identified. Each case was matched by four controls with EGC and margin negative ER but without local recurrence for age, sex, and en-bloc resectability (en-bloc vs. piecemeal resection). Endoscopic data were reviewed by consensus of two endoscopists. Key endoscopic criteria were gross morphology (evenly elevated, unevenly elevated, and flat), hyperemic change, mucosal defect, and spontaneous bleeding. RESULTS: Of 3037 cases, which underwent margin-negative ER, 22 developed local recurrence (mean age, 63.8 years; 72.9% male). En-bloc resection was achieved in 20 of the 22 (90.9%). Flat endoscopic morphology without hyperemic changes predicted non-recurrence at the scar with a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 95.5%, 68.2%, 2.6%, 99.94%, and 73.6%, respectively. For patients who underwent en-bloc resection for differentiated EGC, these values were 100%, 71.4%, 3.0%, 100%, and 75.8%, respectively. CONCLUSIONS: Routine follow-up biopsies may be unnecessary when follow-up endoscopy reveals flat mucosa without hyperemic changes at the scar, especially for en-bloc resected and differentiated EGCs. PMID- 26820102 TI - miR-655 suppresses epithelial-to-mesenchymal transition by targeting Prrx1 in triple-negative breast cancer. AB - Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype that lacks effective targeted therapies. The epithelial-to-mesenchymal transition (EMT) is a key contributor in the metastatic process. In this study, we found that miR-655 was down-regulated in TNBC, and its expression levels were associated with molecular-based classification and lymph node metastasis in breast cancer. These findings led us to hypothesize that miR-655 overexpression may inhibit EMT and its associated traits of TNBC. Ectopic expression of miR-655 not only induced the up-regulation of cytokeratin and decreased vimentin expression but also suppressed migration and invasion of mesenchymal-like cancer cells accompanied by a morphological shift towards the epithelial phenotype. In addition, we found that miR-655 was negatively correlated with Prrx1 in cell lines and clinical samples. Overexpression of miR-655 significantly suppressed Prrx1, as demonstrated by Prrx1 3'-untranslated region luciferase report assay. Our study demonstrated that miR-655 inhibits the acquisition of the EMT phenotype in TNBC by down-regulating Prrx1, thereby inhibiting cell migration and invasion during cancer progression. PMID- 26820103 TI - Molecular characterization and immune response to lipopolysaccharide (LPS) of the suppressor of cytokine signaling (SOCS)-1, 2 and 3 genes in Nile tilapia (Oreochromis niloticus). AB - Suppressor of cytokine signaling (SOCS) proteins are inverse feedback regulators of cytokine and hormone signaling mediated by the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway that are involved in immunity, growth and development of organisms. In the present study, three SOCS genes, SOCS-1, SOCS-2 and SOCS-3, were identified in an economically important fish, Nile tilapia (Oreochromis niloticus) referred to as NtSOCS-1, NtSOCS-2 and NtSOCS-3. Multiple alignments showed that, the three SOCS molecules share highly conserved functional domains, including the SRC homology 2 (SH2) domain, the extended SH2 subdomain (ESS) and the SOCS box with others vertebrate counterparts. Phylogenetic analysis indicated that NtSOCS-1, 2 and 3 belong to the SOCS type II subfamily. Whereas NtSOCS-1 and 3 showed close evolutionary relationship with Perciformes, NtSOCS-2 was more related to Salmoniformes. Tissue specific expression results showed that, NtSOCS-1, 2 and 3 were constitutively expressed in all nine tissues examined. NtSOCS-1 and 3 were highly expressed in immune-related tissues, such as gills, foregut and head kidney. However, NtSOCS-2 was superlatively expressed in liver, brain and heart. In vivo, NtSOCS-1 and 3 mRNA levels were up-regulated after lipopolysaccharide (LPS) challenge while NtSOCS-2 was down-regulated. In vitro, LPS stimulation increased NtSOCS-3 mRNA expression, however it inhibited the transcription of NtSOCS-1 and 2. Collectively, our findings suggest that, the NtSOCS-1 and 3 might play significant role(s) in innate immune response, while NtSOCS-2 may be more involved in metabolic regulation. PMID- 26820104 TI - Identification and characterization of a novel NOD-like receptor family CARD domain containing 3 gene in response to extracellular ATP stimulation and its role in regulating LPS-induced innate immune response in Japanese flounder (Paralichthys olivaceus) head kidney macrophages. AB - Nucleotide oligomerization domain (NOD)-like receptor (NLR) family with a caspase activation and recruitment domain (CARD) containing 3 (NLRC3) protein is an important cytosolic pattern recognition receptor that negatively regulates innate immune response in mammals. Hitherto, the immunological significance of NLRC3 protein in fish remains largely uncharacterized. Here we identified and characterized a novel NLRC3 gene (named poNLRC3) implicated in regulation of fish innate immunity from Japanese flounder Paralichthys olivaceus. The poNLRC3 protein is a cytoplasmic protein with an undefined N-terminal domain, a NACHT domain, a fish-specific NACHT associated domain, six LRR motifs, and a C-terminal fish-specific PYR/SPYR (B30.2) domain but only shares less than 40% sequence identities with the known Japanese flounder NLRC proteins. poNLRC3 gene is ubiquitously expressed in all tested tissues and is dominantly expressed in the Japanese flounder head kidney macrophages (HKMs). We for the first time showed that poNLRC3 expression was significantly modulated by the stimulation of extracellular ATP, an important danger/damage-associated molecular pattern in activating innate immunity in P. olivaceus. Importantly, we revealed that poNLRC3 plays an important role in positively regulating ATP-induced IL-1beta and IL-6 gene expression, suggesting the involvement of poNLRC3 in extracellular ATP mediated immune signaling. In addition, we showed that poNLRC3 mRNA expression was up-regulated in response to LPS and Edwardsiella tarda immune challenges. Finally, we showed that down-regulating the endogenous poNLRC3 expression with small interfering RNA significantly reduced LPS-induced proinflammatory cytokine gene expression in the Japanese flounder HKM cells. Altogether, we have identified a novel inducible fish NLR member, poNLRC3, which is involved in extracellular ATP-mediated immune signaling and may positively regulate the LPS induced innate immune response in the Japanese flounder HKM cells. PMID- 26820105 TI - Sequential energy and electron transfer in a three-component system aligned on a clay nanosheet. AB - To achieve the goal of energy transfer and subsequent electron transfer across three molecules, a phenomenon often utilized in artificial light harvesting systems, we have assembled a light absorber (that also serves as an energy donor), an energy acceptor (that also serves as an electron donor) and an electron acceptor on the surface of an anionic clay nanosheet. Since neutral organic molecules have no tendency to adsorb onto the anionic surface of clay, a positively charged water-soluble organic capsule was used to hold neutral light absorbers on the above surface. A three-component assembly was prepared by the co adsorption of a cationic bipyridinium derivative, cationic zinc porphyrin and cationic octaamine encapsulated 2-acetylanthracene on an exfoliated anionic clay surface in water. Energy and electron transfer phenomena were monitored by steady state fluorescence and picosecond time resolved fluorescence decay. The excitation of 2-acetylanthracene in the three-component system resulted in energy transfer from 2-acetylanthracene to zinc porphyrin with 71% efficiency. Very little loss due to electron transfer from 2-acetylanthracene in the cavitand to the bipyridinium derivative was noticed. Energy transfer was followed by electron transfer from the zinc porphyrin to the cationic bipyridinium derivative with 81% efficiency. Analyses of fluorescence decay profiles confirmed the occurrence of energy transfer and subsequent electron transfer. Merging the concepts of supramolecular chemistry and surface chemistry we realized sequential energy and electron transfer between three hydrophobic molecules in water. Exfoliated transparent saponite clay served as a matrix to align the three photoactive molecules at a close distance in aqueous solutions. PMID- 26820106 TI - New cationic vesicles prepared with double chain surfactants from arginine: Role of the hydrophobic group on the antimicrobial activity and cytotoxicity. AB - Cationic double chain surfactants have attracted much interest because they can give rise to cationic vesicles that can be used in biomedical applications. Using a simple and economical synthetic approach, we have synthesized four double-chain surfactants with different alkyl chain lengths (LANHCx). The critical aggregation concentration of the double chain surfactants is at least one order of magnitude lower than the CMC of their corresponding single-chain LAM and the solutions prepared with the LANHCx contain stable cationic vesicles. Encouragingly, these new arginine derivatives show very low haemolytic activity and weaker cytotoxic effects than conventional dialkyl dimethyl ammonium surfactants. In addition, the surfactant with the shortest alkyl chain exhibits good antimicrobial activity against Gram-positive bacteria. The results show that a rational design applied to cationic double chain surfactants might serve as a promising strategy for the development of safe cationic vesicular systems. PMID- 26820107 TI - Hyaluronic acid-coated niosomes facilitate tacrolimus ocular delivery: Mucoadhesion, precorneal retention, aqueous humor pharmacokinetics, and transcorneal permeability. AB - Tacrolimus (FK506) was used to prevent corneal allograft rejection in patients who were resistant to steroids and cyclosporine. However, the formulation for FK506 ocular delivery remained a challenge due to the drug's high hydrophobicity, high molecular weight, and eye's physiological and anatomical constraints. The aim of this project is to develop an ocular delivery system for FK506 based on a combined strategy of niosomes and mucoadhesive hyaluronic acid (HA), i.e., FK506HA-coated niosomes, which exploits virtues of both niosomes and HA to synergistically improve ophthalmic bioavailability. The FK506HA-coated niosomes were characterized with particle size, zeta potential, and rheology behavior. Mucoadhesion of FK506HA-coated niosomes to mucin was investigated through surface plasmon resonance in comparison with non-coated niosomes and HA solution. The results showed that niosomes possessed adhesion to mucin, and HA coating enhanced the adhesion. The in vivo precorneal retention was evaluated in rabbit, and the results showed that HA-coated niosomes prolonged the residence of FK506 significantly in comparison with non-coated niosomes or suspension. Aqueous humor pharmacokinetics test showed that area under curve of HA-coated niosomes was 2.3 fold and 1.2-fold as that of suspension and non-coated niosomes, respectively. Moreover, the synergetic corneal permeability enhancement of the hybrid delivery system on FK506 was visualized and confirmed by confocal laser scanning microscope. Overall, the results indicated that the hybrid system facilitated FK506 ocular delivery on mucoadhesion, precorneal retention, aqueous humor pharmacokinetics and transcorneal permeability. Therefore, HA-coated niosomes may be a promising approach for ocular targeting delivery of FK506. PMID- 26820109 TI - Angioedema-Urticaria Due to Acitretin. AB - Acitretin is a synthetic oral retinoid that has been used for a number of dermatological diseases. Several side effects of acitretin have been reported such as teratogenicity, cheilitis, xerosis, dyslipidemia, and photosensitivity. Many drugs, mainly antibiotics and nonsteroidal anti-inflammatory drugs, can cause angioedema-urticaria. We present the case of angioedema-urticaria due to acitretin, confirmed by oral provocation test, in a 61-year-old man with psoriasis. To the best of our knowledge, only 1 case of angioedema due to oral acitretin has been reported in the literature so far. We report this case to draw attention that acitretin may cause angioedema-urticaria and to inform patients about this risk besides other side effects due to acitretin. PMID- 26820108 TI - Stromme Syndrome Is a Ciliary Disorder Caused by Mutations in CENPF. AB - Stromme syndrome was first described by Stromme et al. (1993) in siblings presenting with "apple peel" type intestinal atresia, ocular anomalies and microcephaly. The etiology remains unknown to date. We describe the long-term clinical follow-up data for the original pair of siblings as well as two previously unreported siblings with a severe phenotype overlapping that of the Stromme syndrome including fetal autopsy results. Using family-based whole-exome sequencing, we identified truncating mutations in the centrosome gene CENPF in the two nonconsanguineous Caucasian sibling pairs. Compound heterozygous inheritance was confirmed in both families. Recently, mutations in this gene were shown to cause a fetal lethal phenotype, the phenotype and functional data being compatible with a human ciliopathy [Waters et al., 2015]. We show for the first time that Stromme syndrome is an autosomal-recessive disease caused by mutations in CENPF that can result in a wide phenotypic spectrum. PMID- 26820110 TI - Optimised cut-off function for Tersoff-like potentials for a BN nanosheet: a molecular dynamics study. AB - In this article, molecular dynamics based simulations were carried out to study the tensile behaviour of boron nitride nanosheets (BNNSs). Four different sets of Tersoff potential parameters were used in the simulations for estimating the interatomic interactions between boron and nitrogen atoms. Modifications were incorporated in the Tersoff cut-off function to improve the accuracy of results with respect to fracture stress, fracture strain and Young's modulus. In this study, the original cut-off function was optimised in such a way that small and large cut-off distances were made equal, and hence a single cut-off distance was used with all sets of Tersoff potential parameters. The single value of cut-off distance for the Tersoff potential was chosen after analysing the potential energy and bond forces experienced by boron and nitrogen atoms subjected to bond stretching. The simulations performed with the optimised cut-off function help in identifying the Tersoff potential parameters that reproduce the experimentally evaluated mechanical behaviour of BNNSs. PMID- 26820111 TI - "I'm running my depression:" Self-management of depression in neoliberal Australia. AB - The current study examines how the neoliberal imperative to self-manage has been taken up by patients, focusing specifically on Indian-Australians and Anglo Australians living with depression in Australia. We use Nikolas Rose's work on governmentality and neoliberalism to theorise our study and begin by explicating the links between self-management, neoliberalism and the Australian mental health system. Using qualitative methods, comprising 58 in-depth interviews, conducted between May 2012 and May 2013, we argue that participants practices of self management included reduced use of healthcare services, self-medication and self labour. Such practices occurred over time, informed by unsatisfactory interactions with the health system, participants confidence in their own agency, and capacity to craft therapeutic strategies. We argue that as patients absorbed and enacted neoliberal norms, a disconnect was created between the policy rhetoric of self-management, its operationalisation in the health system and patient understandings and practices of self-management. Such a disconnect, in turn, fosters conditions for risky health practices and poor health outcomes. PMID- 26820112 TI - The relationship between international trade and non-nutritional health outcomes: A systematic review of quantitative studies. AB - Markets throughout the world have been reducing barriers to international trade and investment in recent years. The resulting increases in levels of international trade and investment have subsequently generated research interest into the potential population health impact. We present a systematic review of quantitative studies investigating the relationship between international trade, foreign direct investment and non-nutritional health outcomes. Articles were systematically collected from the SCOPUS, PubMed, EconLit and Web of Science databases. Due to the heterogeneous nature of the evidence considered, the 16 included articles were subdivided into individual level data analyses, selected country analyses and international panel analyses. Articles were then quality assessed using a tool developed as part of the project. Nine of the studies were assessed to be high quality, six as medium quality, and one as low quality. The evidence from the quantitative literature suggests that overall, there appears to be a beneficial association between international trade and population health. There was also evidence of the importance of foreign direct investment, yet a lack of research considering the direction of causality. Taken together, quantitative research into the relationship between trade and non-nutritional health indicates trade to be beneficial, yet this body of research is still in its infancy. Future quantitative studies based on this foundation will provide a stronger basis on which to inform relevant national and international institutions about the health consequences of trade policies. PMID- 26820113 TI - Investigating the debate of home birth safety: A critical review of cohort studies focusing on selected infant outcomes. AB - AIM: There is a debate within the medical community regarding the safety of planned home births. The presumption of increased risk of maternal and infant morbidity and mortality at home due to limited access to life-saving interventions is not clearly supported by research. The aim of the present study was to assess strengths and limitations of the methodological approaches of cohort studies that compare home births with hospital births by focusing on selected infant outcomes. METHODS: Studies were identified that assess the risk for at least one of three infant outcomes (mortality, Apgar score, and admission to the neonatal intensive care unit [NICU]) of home births compared with hospital births. RESULTS: Fifteen cohort studies were included. Two studies of low-risk births and two including higher risk births found home births to be at an increased risk of neonatal mortality. However, mortality is rare in developed nations and may not be the best measure of safety. When studies focused on low risk pregnancies, planned birth location, and well-trained birth attendants, there was no difference in neonatal morbidity (Apgar score and NICU admission). CONCLUSION: Many methodological challenges were identified among these studies. This review contributes to the home birth published work by identifying key strengths and limitations that need to be accounted for in the interpretation of study findings and the development of future studies. Based on this review, the key variables that would strengthen future studies are birth attendant identification, documented planned birth location, and specification of the birth risk level. Uniformity of data collection and minimizing missing data are also critical. PMID- 26820114 TI - Improving stroke knowledge through a 'volunteer-led' community education program in Australia. AB - BACKGROUND: Public awareness of stroke risks and warning signs remains poor. The National Stroke Foundation (NSF) in Australia has been undertaking a StrokeSafe Ambassador Education program to raise awareness of stroke. The format includes presentations by volunteers trained to be 'ambassadors' to spread standard information about stroke to the public. Our aim was to determine the change in knowledge of participants who attended presentations. METHODS: Participants completed questionnaires before immediately after presentations, and at 3months following the presentation. Information was collected on knowledge of risk factors and signs of stroke. McNemar's test was used to compare paired-responses over time. A p value of <0.05 was considered significant. RESULTS: Between March and April 2014, 591 participants attended 185 presentations and 591 (100%) completed them before and immediately after presentation questionnaires: 68% were female and 75% were aged 65years or more. 258 consented for further follow-up with 192 completing follow-up. Comparing immediately after with before presentation showed significantly improved knowledge for all 10 stroke risk factors and all signs of stroke. Significantly improved knowledge for 7/10 risk factors and 1/3 signs of stroke was found when comparing follow-up and immediately after presentation results. Knowledge of 5/10 risk factors and 2/3 signs of stroke improved when comparing follow-up and before presentation. CONCLUSION: This study describes a novel approach to support the use of trained volunteers to provide a community-based, standardised education program for stroke. This program shows that community presentations can improve immediate and short-term knowledge of signs and risk factors for stroke. PMID- 26820115 TI - Spatial analysis of crime incidence and adolescent physical activity. AB - OBJECTIVES: Adolescents do not achieve recommended levels of physical activity. Crime is believed to be a barrier to physical activity among youth, but findings are inconsistent. This study compares the spatial distribution of crime incidences and moderate-to-vigorous physical activity (MVPA) among adolescents in Massachusetts between 2011 and 2012, and examines the correlation between crime and MVPA. METHODS: Eighty adolescents provided objective physical activity (accelerometer) and location (Global Positioning Systems) data. Crime report data were obtained from the city police department. Data were mapped using geographic information systems, and crime and MVPA densities were calculated using kernel density estimations. Spearman's correlation tested for associations between crime and MVPA. RESULTS: Overall, 1694 reported crimes and 16,702min of MVPA were included in analyses. A strong positive correlation was present between crime and adolescent MVPA (rho=0.72, p<0.0001). Crime remained positively associated with MVPA in locations falling within the lowest quartile (rho=0.43, p<0.0001) and highest quartile (rho=0.32, p<0.0001) of crime density. CONCLUSIONS: This study found a strong positive association between crime and adolescent MVPA, despite research suggesting the opposite relationship. This counterintuitive finding may be explained by the logic of a common destination: neighborhood spaces which are desirable destinations and promote physical activity may likewise attract crime. PMID- 26820116 TI - Evolution of the protease-activated receptor family in vertebrates. AB - Belonging to the G protein-coupled receptor (GPcr) family, the protease-activated receptors (Pars) consist of 4 members, PAR1-4. PARs mediate the activation of cells via thrombin, serine and other proteases. Such protease-triggered signaling events are thought to be critical for hemostasis, thrombosis and other normal pathological processes. In the present study, we examined the evolution of PARs by analyzing phylogenetic trees, chromosome location, selective pressure and functional divergence based on the 169 functional gene alignment sequences from 57 vertebrate gene sequences. We found that the 4 Pars originated from 4 invertebrate ancestors by phylogenetic trees analysis. The selective pressure results revealed that only PAR1 appeared by positive selection during its evolution, while the other PAR members did not. In addition, we noticed that although these PARs evolved separately, the results of functional divergence indicated that their evolutional rates were similar and their functions did not significantly diverge. The findings of our study provide valuable insight into the evolutionary history of the vertebrate PAR family. PMID- 26820117 TI - Loop-mediated isothermal amplification for detection of the tomato and potato late blight pathogen, Phytophthora infestans. AB - AIMS: To design and validate a colorimetric loop-mediated isothermal amplification assay for rapid detection of Phytophthora infestans DNA. METHODS AND RESULTS: Two sets of loop-mediated isothermal amplification (LAMP) primers were designed and evaluated for their sensitivity and specificity for P. infestans. ITSII primers targeted a portion of the internal transcribed spacer region of ribosomal DNA. These primers had a limit of detection of 2 pg P. infestans DNA and cross-reacted with the closely related species Phytophthora nicotianae. Rgn86_2 primers, designed to improve assay specificity, targeted a portion of a conserved hypothetical protein. These primers had a limit of detection of 200 pg P. infestans DNA and did not cross-react with P. nicotianae. The specificity of the Rgn86_2 assay was tested further using the closely related species P. andina, P. ipomoeae, P. mirabilis and P. phaseoli. Cross-reactions occurred with P. andina and P. mirabilis, but neither species occurs on tomato or potato. Both primer sets were able to detect P. infestans DNA extracted from tomato late blight leaf lesions. CONCLUSIONS: Two colorimetric LAMP assays detected P. infestans DNA from pure cultures as well as infected leaf tissue. The ITSII primers had higher sensitivity, and the Rgn86_2 primers had higher specificity. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of a LAMP assay for the detection of P. infestans, the causal organism of potato and tomato late blight. These assays have potential for immediate utility in plant disease research and diagnostic laboratories. PMID- 26820118 TI - Concealed Epispadias: Report of Two Cases and Review of Literature. AB - OBJECTIVE: To present an overview of the clinical presentation and pathological anatomy of epispadias with intact prepuce--a rare condition that has only occasionally been reported in literature. MATERIALS AND METHODS: We present two cases of concealed epispadias. We also review the available literature with regard to this rare condition. We found 14 cases in 7 studies that were reviewed. Relevant variables were reviewed and are discussed. RESULTS: There were 13 of 16 cases presented with complaints of buried or webbed penis. In 11 of 16 cases, epispadias was suspected or diagnosed at first presentation and could be surgically corrected in the first intervention. Epispadias repair was successful with regard to cosmesis and erectile function in all cases, including ours. CONCLUSION: Proper preoperative diagnosis and preoperative counseling of parents are essential for the successful treatment of this rare entity. Fewer complications, less additional interventions, and better continence rates seem to be noted for the boys with epispadias and intact prepuce. PMID- 26820119 TI - Reply by the Authors. PMID- 26820120 TI - Epigallocatechin Gallate Attenuates Partial Bladder Outlet Obstruction-induced Bladder Injury via Suppression of Endoplasmic Reticulum Stress-related Apoptosis In Vivo Study. AB - OBJECTIVES: To investigate the protective effect of epigallocatechin gallate (EGCG), a green tea extract, on partial bladder outlet obstruction (pBOO)-induced bladder injury in a rat model. METHODS: The female Sprague-Dawley rats underwent sham or BOO procedures, and were divided into several groups (sham with saline injection, sham with EGCG treatment, BOO with saline injection, and BOO with EGCG treatment). The rats in each group were randomized into 2 groups (48 hours and 30 days after the BOO procedure) for when their bladders were harvested. EGCG (4.5 mg/kg/day) and saline were administered via intraperitoneal injection after the BOO procedure during the study period. Bladder tissue was examined for inflammation, endoplasmic reticulum (ER) stress-related apoptotic markers by Western blot, and histological staining. RESULTS: BOO induced acute bladder injury (hemorrhage, edema, and neutrophil infiltration) after 48 hours. In addition, cystometry showed a decrease in micturition pressure and intercontractile interval. We also observed increased expressions of cyclooxygenase-2, poly(ADP-ribose) polymerase at 48 hours, as well as ER stress markers such as caspase-12 and CCAAT/-enhancer-binding protein homologous protein (CHOP). Treatment with EGCG significantly improved pBOO-induced histologic changes, bladder dysfunction, and the overexpression of cyclooxygenase-2, CHOP, and caspase-12 at 48 hours. Similarly, EGCG treatment for 30 days effectively recovered compliance and intercontractile interval, submucosal ER stress-related apoptosis (CHOP and caspase-12) at 30 days after pBOO. CONCLUSIONS: EGCG alleviate pBOO-induced bladder injury and dysfunction via suppression of inflammation and ER stress-related apoptosis. PMID- 26820121 TI - MiRNA-10b sponge: An anti-breast cancer study in vitro. AB - Breast cancer is a malignant tumor with the highest incidence among women. Breast cancer metastasis is the major cause of treatment failure and mortality among such patients. MicroRNAs (miRNAs) are a class of small molecular non-coding regulatory RNAs, which act as oncogenes or tumor suppressors in breast cancer. miRNA-10b has been found to exhibit a high expression level in advanced and metastatic breast cancer, and is closely related to breast cancer metastasis. An miRNA sponge is an mRNA with several repeated sequences of complete or incomplete complementarity to the natural miRNA in its 3' non-translating region. It acts as a sponge adsorbing miRNAs and ensures their separation from their targets and inhibits their function. The present study designed a sponge plasmid against miRNA-10b and transiently transfected it into high and low metastatic human breast cancer cell lines MDA-MB-231 and MCF-7, and analyzed the effects of the miRNA-10b sponge on the growth and proliferation, migration and invasion in these cell lines. qRT-PCR results found that the sponge plasmid effectively inhibited the expression of miRNA-10b, and upregulated the expression of the miRNA-10b target protein HOXD-10. The results from the CCK-8 assay found that the miRNA-10b sponge inhibited the growth of breast cancer cell lines MDA-MB-231 and MCF-7. Results of the plate cloning experiments indicated that the miRNA-10b sponge suppressed the colony formation of the MDA-MB-231 and MCF-7 cells. The results of wound healing and Transwell assays showed that the miRNA-10b sponge inhibited the migration and invasion of the breast cancer cell lines MDA-MB-231 and MCF-7. Our results demonstrated that the miRNA-10b sponge effectively inhibited the growth and proliferation of breast cancer MDA-MB-231 and MCF-7 cells. In addition, it also restrained the migration and invasion of human highly metastatic breast cancer MDA-MB-231 cells. PMID- 26820122 TI - Lignin enrichment and enzyme deactivation as the root cause of enzymatic hydrolysis slowdown of steam pretreated sugarcane bagasse. AB - The enzymatic hydrolysis (EH) rate normally decreases during the hydrolysis, leaving unhydrolyzed material as residue. This phenomenon occurs during the hydrolysis of both cellulose (avicel) and lignocellulosic material, in nature or even pretreated. The progression of EH of steam pretreated sugarcane bagasse was associated with an initial (fast), intermediate (slower) and recalcitrant (slowest) phases, at glucan to glucose conversion yields of 61.7, 81.6 and 86%, respectively. Even though the EH of avicel as a simpler material than steam pretreated sugarcane bagasse, EH slowdown was present. The less thermo-stable endo-xylanase lost 58% of initial enzyme activity, followed by beta-glucosidase that lost 16%, culminating in FPase activity loss of 30% in the first 24hours. After 72hours of EH the total loss of FPase activity was 40% compared to the initial activity. Analysis of the solid residue from EH showed that lignin content, phenolic compounds and ash increased while glucan decreased as hydrolysis progressed. During the initial fast phase of EH, the total solid residue surface area consisted predominantly of internal surface area. Thereafter, in the intermediate and recalcitrant phases of EH, the ratio of external:internal surface area increased. The proposed fiber damage and decrease in internal surface area, probably by EH action, was visualized by scanning electron microscopy imagery. The higher lignin/glucan ratio as EH progressed and enzyme deactivation by thermo instability were the main effects observed, respectively to substrate and enzyme. PMID- 26820123 TI - Construction of a highly active secretory expression system via an engineered dual promoter and a highly efficient signal peptide in Bacillus subtilis. AB - A strong promoter and highly efficient signal peptides are essential for the secretory overproduction of recombinant proteins in Bacillus subtilis. To enhance the limited overexpression capability of natural promoters, various strategies for promoter engineering have been developed and used to construct gene expression systems in B. subtilis and other hosts. By applying a semi-rational approach for promoter engineering, a series of expression plasmids containing single and dual promoters were constructed using aminopeptidase (AP) with an intrinsic signal peptide as the reporter protein. Of the single and dual promoters investigated, the dual promoter PgsiB-PHpaII gave the best performance. To optimize secretion efficiency, the signal peptide YncM was selected after screening a library containing 19 different Sec-type signal peptides. The AP activity detected in the supernatants of a recombinant strain containing the plasmid pBSG24-YncM was as high as 88.86U/mL. The capacity of the expression plasmid pBSG24-YncM was also evaluated with batch fermentation in a 5-L fermentor. Increased production of AP (205U/mL, equal to 1.7g/L) was achieved after 45h of fermentation. These results suggest that this expression system can be used for high-level protein expression in B. subtilis. PMID- 26820124 TI - Comparison of quantitative real-time polymerase chain reaction with NanoString(r) methodology using adipose and liver tissues from rats fed seaweed. AB - Experimental methods are constantly being improved by new technology. Recently a new technology, NanoString(r), has been introduced to the market for the analysis of gene expression. Our experiments used adipose and liver samples collected from a rat feeding trial to explore gene expression changes resulting from a diet of 7.5% seaweed. Both quantitative real-time polymerase chain reaction (qPCR) and NanoString methods were employed to look at expression of genes related to fat and glucose metabolism and this paper compares results from both methods. We conclude that NanoString offers a valuable alternative to qPCR and our data suggest that results are more accurate because of the reduced sample handling and direct quantification of gene copy number without the need for enzymatic amplification. However, we have highlighted a potential challenge for both methods, which needs to be addressed when designing primers or probes. We suggest a literature search for known splice variants of a particular gene to be completed so that primers or probes can be designed that do not span exons which may be affected by alternative gene sequences. PMID- 26820126 TI - How maternal malnutrition affects linear growth and development in the offspring. AB - Maternal malnutrition is common in the developing world and has detrimental effects on both the mother and infant. Pre-pregnancy nutritional status and weight gain during pregnancy are positively related to fetal growth and development. Internationally, there is no agreement on the method of diagnosis or treatment of moderate or severe malnutrition during pregnancy. Establishing clear guidelines for diagnosis and treatment will be essential in elevating the problem. Possible anthropometric measurements used to detect and monitor maternal malnutrition include pre-pregnancy BMI, weight gain, and mid upper arm circumference. Food supplements have the potential to increase gestational weight gain and energy intake which are positively associated with fetal growth and development. Overall more studies are needed to conclude the impact of food/nutrient supplements on infant growth in undernourished pregnant women in developing countries. Currently, a study underway may provide much needed documentation of the benefits of treating malnutrition in pregnancy. PMID- 26820125 TI - Pancreatic islet hepatocyte growth factor and vascular endothelial growth factor A signaling in growth restricted fetuses. AB - Placental insufficiency leads to intrauterine growth restriction (IUGR) and a lifelong risk of developing type 2 diabetes. Impaired islet development in the growth restricted fetus, including decreased beta-cell replication, mass, and insulin secretion, is strongly implicated in the pathogenesis of later life type 2 diabetes. Currently, standard medical management of a woman with a pregnancy complicated by placental insufficiency and fetal IUGR is increased fetal surveillance and indicated preterm delivery. This leads to the dual complications of IUGR and preterm birth - both of which may increase the lifelong risk for type 2 diabetes. In order to develop therapeutic interventions in IUGR pregnancies complicated by placental insufficiency and decrease the risk of later development of type 2 diabetes in the offspring, the mechanisms responsible for impaired islet development in these cases must be determined. This review focuses on current investigations testing the hypothesis that decreased nutrient supply to the IUGR fetus inhibits an intra-islet hepatocyte growth factor - vascular endothelial growth factor A (HGF - VEGFA) feed forward signaling pathway and that this is responsible for developmental islet defects. PMID- 26820127 TI - 3,5-Diiodothyronine-mediated transrepression of the thyroid hormone receptor beta gene in tilapia. Insights on cross-talk between the thyroid hormone and cortisol signaling pathways. AB - T3 and cortisol activate or repress gene expression in virtually every vertebrate cell mainly by interacting with their nuclear hormone receptors. In contrast to the mechanisms for hormone gene activation, the mechanisms involved in gene repression remain elusive. In teleosts, the thyroid hormone receptor beta gene or thrb produces two isoforms of TRbeta1 that differ by nine amino acids in the ligand-binding domain of the long-TRbeta1, whereas the short-TRbeta1 lacks the insert. Previous reports have shown that the genomic effects exerted by 3,5-T2, a product of T3 outer-ring deiodination, are mediated by the long-TRbeta1. Furthermore, 3,5-T2 and T3 down-regulate the expression of long-TRbeta1 and short TRbeta1, respectively. In contrast, cortisol has been shown to up-regulate the expression of thrb. To understand the molecular mechanisms for thrb modulation by thyroid hormones and cortisol, we used an in silico approach to identify thyroid- and cortisol-response elements within the proximal promoter of thrb from tilapia. We then characterized the identified response elements by EMSA and correlated our observations with the effects of THs and cortisol upon expression of thrb in tilapia. Our data show that 3,5-T2 represses thrb expression and impairs its up regulation by cortisol possibly through a transrepression mechanism. We propose that for thrb down-regulation, ligands other than T3 are required to orchestrate the pleiotropic effects of thyroid hormones in vertebrates. PMID- 26820128 TI - miR-152 functions as a tumor suppressor in colorectal cancer by targeting PIK3R3. AB - Accumulating evidence showed that microRNA-152 (miR-152) was frequently downregulated, and functioned as tumor suppressor in many cancers, but little is known about its biological role and intrinsic regulatory mechanisms in colorectal cancer (CRC). Here, we explored the potential role of miR-152 in CRC and the possible molecular mechanisms. Our results proved that miR-152 expression was downregulated in CRC cell lines and tissue samples, and its expression was inversely correlated with advanced tumor-node-metastasis (TNM) stage (P < 0.01) and lymph node metastasis (P < 0.01). Function assays demonstrated that restoring the expression of miR-152 in CRC cells dramatically reduced the cell proliferation and cell migration and invasion and promoted apoptosis and caspase 3 activity in vitro, as well as suppressed tumor growth in vivo. Mechanistic investigations defined phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) as a direct and functional downstream target of miR-152. In addition, we also found that PIK3R3 expression was upregulated and was inversely correlated with miR-152 expression in clinical CRC tissues. Downregulation of PIK3R3 mimicked the tumor suppressive effects of miR-152 overexpression in CRC cells. Taken together, these results elucidated the function of miR-152 in CRC progression and suggested that miR-152 might function as tumor suppressor in CRC by targeting PIK3R3. PMID- 26820129 TI - A novel anti-alpha-fetoprotein single-chain variable fragment displays anti-tumor effects in HepG2 cells as a single agent or in combination with paclitaxel. AB - Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival time. The function of alpha fetoprotein (AFP) as a regulatory factor in the growth of HCC cells has been well defined. The aim of this study was to investigate the use of a novel AFP-specific single-chain variable fragment that blocked AFP and inhibited HCC cell growth. The results indicated that the anti-AFP single-chain variable fragment (scFv) induced growth inhibition of AFP-expressing HCC cell lines in vitro through induction of G1 cell cycle arrest and apoptosis. The mechanism of apoptosis probably involved with blocking AFP internalization and regulation of the PTEN/PI3K/Akt signaling network. Moreover, the anti-AFP-scFv also effectively sensitized the HepG2 cells to paclitaxel (PTX) at a lower concentration. The combination effect of PTX and anti-AFP-scFv displayed a synergistic effect on HepG2 cells both in vitro and in vivo. Our results demonstrated that targeting AFP by specific antibodies has potential immunotherapeutic efficacy in human HCC. PMID- 26820130 TI - Long non-coding RNA AK027294 involves in the process of proliferation, migration, and apoptosis of colorectal cancer cells. AB - This study is aimed to investigate the differentially expressed long non-coding RNAs (lncRNAs) in colorectal cancer and its potential biological function. Colorectal adenoma is the precancerous lesions of colorectal cancer, so in this study, we used colorectal adenoma as negative control. The global lncRNA expression profile in colorectal cancer and adenoma was evaluated by bioinformatics. The biological functions and potential mechanism of AK027294 were investigated in HCT116, HCT8, and SW480 colorectal cancer cells. A total of 135 lncRNAs were found to be differentially expressed in colorectal cancer and adenoma tissues. Among them, 71 lncRNAs were up-regulated and 64 lncRNAs were down-regulated. Especially, AK027294 was found to be highly expressed in colorectal cancer tissues compared with colorectal adenoma tissues (fold change is 184.5). Our results indicated that AK027294 down-regulation significantly inhibited colorectal cancer cells proliferation and migration, but promoted cell apoptosis (P < 0.05). The potential mechanism of AK027294 might be associated with the regulation of caspase-3, caspase-8, Bcl-2, MMP12, MMP9, and TWIST. The lncRNA expression profile in colorectal cancer suggests lncRNAs may play important roles in the occurrence and progression of colorectal cancer. AK027294 is highly expressed in colorectal cancer and closely correlates with colorectal cells proliferation, migration, and apoptosis. PMID- 26820132 TI - Erratum to: Increased expression of MyD88 and association with paclitaxel resistance in breast cancer. PMID- 26820131 TI - The prognostic implication of SRSF2 mutations in Chinese patients with acute myeloid leukemia. AB - Recently, somatic mutations in SRSF2 gene have been discovered in a proportion of hematologic malignancies including acute myeloid leukemia (AML). This study was aimed to investigate SRSF2 mutations in Chinese AML patients. High-resolution melting analysis (HRMA) was developed to screen SRSF2 mutations in 249 cases with AML, and then direct DNA sequencing was used to verify the results of HRMA. In this study, 3.6 % (9/249) of Chinese AML patients were found with heterozygous SRSF2 mutations. Patients with SRSF2 mutations were older than those with wild type SRSF2 (P = 0.014). No differences in the sex, blood parameters, French American-British classification (FAB) subtypes, and karyotypes were observed between AML patients with and without SRSF2 mutations. Although the overall survival (OS) of SRSF2-mutated patients was inferior to those without mutations in both whole AML patients (median 4 vs. 11 months, respectively; P = 0.006) and cytogenetically normal patients (median 2 vs. 12 months, respectively; P = 0.008), multiple analysis disclosed that SRSF2 mutation was not an independent prognostic factor in AML patients. These results suggest that SRSF2 mutation occurs at a low frequency in aged AML patients and might not be associated with adverse prognosis in Chinese AML patients. PMID- 26820133 TI - Use of two gene panels for prostate cancer diagnosis and patient risk stratification. AB - Currently, no ideal prostate cancer (PCa) diagnostic or prognostic test is available due to the lack of biomarkers with high sensitivity and specificity. There is an unmet medical need to develop combinations of multiple biomarkers which may have higher accuracy in detection of PCa and stratification of aggressive and indolent cancer patients. The aim of this study was to test two biomarker gene panels in distinguishing PCa from benign prostate and high-risk, aggressive PCa from low-risk, indolent PCa, respectively. We identified a five gene panel that can be used to distinguish PCa from benign prostate. The messenger RNA (mRNA) expression signature of the five genes was determined in 144 PCa and benign prostate specimens from prostatectomy. We showed that the five gene panel distinguished PCa from benign prostate with sensitivity of 96.59 %, specificity of 92.86 %, and area under the curve (AUC) of 0.992 (p < 0.0001). The five-gene panel was further validated in a 137 specimen cohort and showed sensitivity of 84.62 %, specificity of 91.84 %, and AUC of 0.942 (p < 0.0001). To define subtypes of PCa for treatment guidance, we examined mRNA expression signature of an eight-gene panel in 87 PCa specimens from prostatectomy. The signature of the eight-gene panel was able to distinguish aggressive PCa (Gleason score >6) from indolent PCa (Gleason score <=6) with sensitivity of 90.28 %, specificity of 80.00 %, and AUC of 0.967 (p < 0.0001). This panel was further validated in a 158 specimen cohort and showed significant difference between aggressive PCa and indolent PCa with sensitivity of 92.57 %, specificity of 70.00 %, and AUC of 0.962 (p < 0.0001). Our findings in assessing multiple biomarkers in combination may provide new tools to detect PCa and distinguish aggressive and indolent PCa for precision and personalized treatment. The two biomarker panels may be used in clinical settings for accurate PCa diagnosis and patient risk stratification for biomarker-guided treatment. PMID- 26820134 TI - Effect of Antimicrobial Consumption and Production Type on Antibacterial Resistance in the Bovine Respiratory and Digestive Tract. AB - The aim of this study was to investigate the relationship between antimicrobial use and the occurrence of antimicrobial resistance in the digestive and respiratory tract in three different production systems of food producing animals. A longitudinal study was set up in 25 Belgian bovine herds (10 dairy, 10 beef, and 5 veal herds) for a 2 year monitoring of antimicrobial susceptibilities in E. coli and Pasteurellaceae retrieved from the rectum and the nasal cavity, respectively. During the first year of observation, the antimicrobial use was prospectively recorded on 15 of these farms (5 of each production type) and transformed into the treatment incidences according to the (animal) defined daily dose (TIADD) and (actually) used daily dose (TIUDD). Antimicrobial resistance rates of 4,174 E. coli (all herds) and 474 Pasteurellaceae (beef and veal herds only) isolates for 12 antimicrobial agents demonstrated large differences between intensively reared veal calves (abundant and inconstant) and more extensively reared dairy and beef cattle (sparse and relatively stable). Using linear mixed effect models, a strong relation was found between antimicrobial treatment incidences and resistance profiles of 1,639 E. coli strains (p<0.0001) and 309 Pasteurellaceae (p<=0.012). These results indicate that a high antimicrobial selection pressure, here found to be represented by low dosages of oral prophylactic and therapeutic group medication, converts not only the commensal microbiota from the digestive tract but also the opportunistic pathogenic bacteria in the respiratory tract into reservoirs of multi-resistance. PMID- 26820135 TI - Cohort Differences in Psychosocial Function over 20 Years: Current Older Adults Feel Less Lonely and Less Dependent on External Circumstances. AB - BACKGROUND: Lifespan psychological and life course sociological perspectives indicate that individual development is shaped by social and historical circumstances. Increases in fluid cognitive performance over the last century are well documented and researchers have begun examining historical trends in personality and subjective well-being in old age. Relatively less is known about secular changes in other key components of psychosocial function among older adults. OBJECTIVE: In the present study, we examined cohort differences in key components of psychosocial function, including subjective age, control beliefs, and perceived social integration, as indicated by loneliness and availability of very close others. METHODS: We compared data obtained 20 years apart in the Berlin Aging Study (in 1990-1993) and the Berlin Aging Study II (in 2013-2014) and identified case-matched cohort groups based on age, gender, cohort-normed education, and marital or partner status (n = 153 in each cohort, mean age = 75 years). In follow-up analyses, we controlled for having lived in former East versus West Germany, physical diseases, cohort-normed household income, cognitive performance, and the presence of a religious affiliation. RESULTS: Consistently across analyses, we found that, relative to the earlier-born BASE cohort (year of birth: mean = 1916; SD = 3.38 years; range = 1901-1922), participants in the BASE II sample (year of birth: mean = 1939; SD = 3.22 years; range = 1925-1949) reported lower levels of external control beliefs (d = -1.01) and loneliness (d = -0.63). Cohorts did not differ in subjective age, availability of very close others, and internal control beliefs. CONCLUSION: Taken together, our findings suggest that some aspects of psychosocial function of older adults have improved across the two recent decades. We discuss the possible role of sociocultural factors that might have led to the observed set of cohort differences. PMID- 26820136 TI - WRKY1 regulates stomatal movement in drought-stressed Arabidopsis thaliana. AB - A key response of plants to moisture stress is stomatal closure, a process mediated by the phytohormone abscisic acid (ABA). Closure is affected by changes in the turgor of the stomatal guard cell. The transcription factor WRKY1 is a part of the regulatory machinery underlying stomatal movements, and through this, in the plant's response to drought stress. The loss-of-function T-DNA insertion mutant wrky1 was particularly sensitive to ABA, with respect to both ion channel regulation and stomatal movements, and less sensitive to drought than the wild type. Complementation of the wrky1 mutant resulted in the recovery of the wild type phenotype. The WRKY1 product localized to the nucleus, and was shown able to bind to the W-box domain in the promoters of MYB2, ABCG40, DREB1A and ABI5, and thereby to control their transcription in response to drought stress or ABA treatment. WRKY1 is thought to act as a negative regulator in guard cell ABA signalling. PMID- 26820138 TI - Functional analysis of three BrMYB28 transcription factors controlling the biosynthesis of glucosinolates in Brassica rapa. AB - Glucosinolates (GSLs) are secondary metabolites that have anticarcinogenic activity and play defense roles in plants of the Brassicaceae family. MYB28 is known as a transcription factor that regulates aliphatic GSL biosynthesis in Arabidopsis thaliana. Brassicaceae plants have three orthologous copies of AtMYB28 derived from recent genome triplication. These BrMYB28 genes have a high level of sequence homology, with 81-87% similarities in the coding DNA sequence compared to Arabidopsis. Overexpression of three paralogous BrMYB28 genes in transgenic Chinese cabbage increased the total GSL content in all T1 generation plants and in two inbred lines of homozygous T2 plants. The highest total GSL contents were detected in homozygous T2 lines overexpressing BrMYB28.1, which showed an approximate fivefold increase compared to that of nontransgenic plants. The homozygous T2 lines with overexpressed BrMYB28.1 also showed an increased content of aliphatic, indolic, and aromatic GSLs compared to that of nontransgenic plants. Furthermore, all of the three BrMYB28 genes were identified as negative regulators of BrAOP2 and positive regulators of BrGSL-OH in the homozygous T2 lines. These data indicate the regulatory mechanism of GSL biosynthesis in B. rapa is unlike that in A. thaliana. Our results will provide useful information for elucidating the regulatory mechanism of GSL biosynthesis in polyploid plants. PMID- 26820137 TI - Co-expression network analysis reveals transcription factors associated to cell wall biosynthesis in sugarcane. AB - Sugarcane is a hybrid of Saccharum officinarum and Saccharum spontaneum, with minor contributions from other species in Saccharum and other genera. Understanding the molecular basis of cell wall metabolism in sugarcane may allow for rational changes in fiber quality and content when designing new energy crops. This work describes a comparative expression profiling of sugarcane ancestral genotypes: S. officinarum, S. spontaneum and S. robustum and a commercial hybrid: RB867515, linking gene expression to phenotypes to identify genes for sugarcane improvement. Oligoarray experiments of leaves, immature and intermediate internodes, detected 12,621 sense and 995 antisense transcripts. Amino acid metabolism was particularly evident among pathways showing natural antisense transcripts expression. For all tissues sampled, expression analysis revealed 831, 674 and 648 differentially expressed genes in S. officinarum, S. robustum and S. spontaneum, respectively, using RB867515 as reference. Expression of sugar transporters might explain sucrose differences among genotypes, but an unexpected differential expression of histones were also identified between high and low Brix degrees genotypes. Lignin biosynthetic genes and bioenergetics related genes were up-regulated in the high lignin genotype, suggesting that these genes are important for S. spontaneum to allocate carbon to lignin, while S. officinarum allocates it to sucrose storage. Co-expression network analysis identified 18 transcription factors possibly related to cell wall biosynthesis while in silico analysis detected cis-elements involved in cell wall biosynthesis in their promoters. Our results provide information to elucidate regulatory networks underlying traits of interest that will allow the improvement of sugarcane for biofuel and chemicals production. PMID- 26820139 TI - Symbiotic Bacteria in Gills and Guts of Chinese Mitten Crab (Eriocheir sinensis) Differ from the Free-Living Bacteria in Water. AB - Aquatic animals have a close relationship with water, but differences in their symbiotic bacteria and the bacterial composition in water remains unclear. Wild or domestic Chinese mitten crabs (Eriocheir sinensis) and the water in which they live were collected from four sampling sites in Jiangsu and Shanghai, China. Bacterial composition in water, gills or guts of E. sinensis, were compared by high-throughput sequencing using 16S rRNA genes. Analysis of >660,000 sequences indicated that bacterial diversity was higher in water than in gills or guts. Tenericutes and Proteobacteria were dominant phyla in guts, while Actinobacteria, Proteobacteria and Bacteroidetes were dominant in gills and water. Non-metric multidimensional scaling analysis indicated that microbiota from gills, guts or water clearly separated into three groups, suggesting that crabs harbor a more specific microbial community than the water in which they live. The dominant OTUs in crab gut were related to Mycoplasmataceae, which were low in abundance in gills, showing that, like mammals, crabs have body-site specific microbiota. OTUs related to Ilumatobacter and Albimonas, which are commonly present in sediment and seawater, were dominant in gills but almost absent from the sampled water. Considering E. sinensis are bottom-dwelling crustacean and they mate in saline water or seawater, behavior and life cycle of crabs may play an important role in shaping the symbiotic bacterial pattern. This study revealed the relationship between the symbiotic bacteria of Chinese mitten crab and their habitat, affording information on the assembly factors of commensal bacteria in aquatic animals. PMID- 26820140 TI - Effect of waterborne zinc exposure on lipid deposition and metabolism in hepatopancreas and muscle of grass carp Ctenopharyngodon idella. AB - The aim of the present study was to explore the effect of waterborne zinc (control, 0.85, 2.20, 3.10 mg/l, respectively) exposure on lipid deposition and metabolism in the hepatopancreas and muscle of grass carp Ctenopharyngodon idella. The lipid content, Zn accumulation, and the activities and expression levels of several enzymes involved in lipid metabolism were determined in hepatopancreas and muscle. Waterborne Zn exposure reduced growth performance and increased Zn accumulation in both tested tissues. In hepatopancreas, Zn exposure increased lipid content, the activities of lipogenic enzymes, such as 6PGD, G6PD, ME, ICDH and FAS, as well as the mRNA expression level of G6PD, 6PGD, ICDH, FAS and SREBP-1. But the activity of CPT I and the mRNA expression of HSL, CPT Ialpha1a, CPT Ialpha2a and PPARalpha were down-regulated by Zn exposure. In contrast, in muscle, waterborne Zn exposure decreased lipid deposition, activities of 6GPD, ICDH and ME, as well as the mRNA expression level of G6PD, ICDH, ME, FAS and SREBP-1. However, the activity of CPT I as well as the mRNA expression level of PPARalpha, HSL, CPT Ialpha2a, CPT Ialpha1b and CPT Ibeta were up-regulated by Zn exposure. Our results indicate that waterborne Zn increases lipid content by up-regulating lipogenesis and down-regulating lipolysis in hepatopancreas. But, in muscle, waterborne Zn reduces lipid accumulation by up regulating lipolysis and down-regulating lipogenesis. Differential patterns of lipid deposition, enzymatic activities and genes' expression indicate the tissue specific regulatory mechanism in fish. PMID- 26820141 TI - Two HSP90 genes in mandarin fish Siniperca chuatsi: identification, characterization and their specific expression profiles during embryogenesis and under stresses. AB - HSP90 plays important roles in multiple cellular stress responses. Here, two cytoplasmic HSP90 isoforms, ScHSP90alpha and ScHSP90beta, were identified from Siniperca chuatsi. Their cDNA and gDNA structures, amino acid sequence features, and sequence identities and phylogenetic analysis with other species were described. Their expression profiles during embryonic development in different tissues and under stressful conditions were analyzed using real-time quantitative PCR. During embryogenesis, transcripts of both genes were detected at low levels during the early developmental stages and were up-regulated from appearance of myomere for ScHSP90a and closure of blastopore for ScHSP90beta. ScHSP90alpha showed a tissue-specific variation with high expression in ovary and brain under non-stressed conditions, while ScHSP90beta was ubiquitously highly expressed in different tissues. Acute heat shock resulted in a strong up-regulation of ScHSP90alpha in heart, liver, and head kidney, while it only weakly induced ScHSP90beta in these tissues. ScHSP90alpha was also markedly induced in liver in a time-dependent manner under hypoxia, while the expression of ScHSP90beta was not affected by hypoxia. Additionally, Aeromonas hydrophila infection markedly augmented ScHSP90alpha in head kidney and spleen and mildly up-regulated ScHSP90beta in spleen, while suppressing ScHSP90beta in head kidney. These results suggest that ScHSP90alpha and ScHSP90beta are differently involved in embryogenesis and under different environmental conditions including high temperature, hypoxia, and bacterial infection. This study will benefit to further clarify the roles of fish HSP90 isoforms in embryogenesis and under stressful conditions and contribute to further study on enhancing stress tolerance and disease resistance of mandarin fish. PMID- 26820142 TI - Lifestyle behaviors among US cancer survivors. AB - PURPOSE: We describe and compare lifestyle behaviors, including smoking, physical activity, alcohol consumption, and nutrition, among cancer survivors to individuals with no cancer. METHODS: Data from the 2013 Behavior Risk Factor Surveillance System were used for this cross-sectional study. Weighted analysis was performed, and associations were examined by adjusted prevalence ratios (APRs) and 95 % confidence intervals (CIs). RESULTS: Comparing survivors to individuals with no cancer history, differences were found for a smoking quit attempt (APR 1.08; CI 1.04, 1.12), physical inactivity (APR 1.11; CI 1.07, 1.15), and binge drinking (APR 0.89; CI 0.83, 0.95). An interaction with gender was observed when examining smoking and heavy drinking. Smoking was lower (APR 0.85; CI 0.79, 0.92) among male survivors than males with no cancer history, while higher (APR 1.25; CI 1.18, 1.32) among female survivors compared to females with no cancer history. Heavy drinking (APR 0.85; CI 0.73, 0.98) was lower among male survivors than males with no cancer history, while cancer survivorship was not associated with heavy drinking among females. No differences existed for fruit and vegetable consumption or body mass index. CONCLUSIONS: US cancer survivors are not more likely than the general population to engage in all healthy lifestyle behaviors. Interventions, including improved physician communication, to reduce physical inactivity among all cancer survivors and cigarette smoking among female survivors are needed. IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivors are at increased risk for comorbid conditions, and acceptance of healthy behaviors may reduce dysfunction and improve long-term health. Ultimately, opportunities exist for clinicians to promote lifestyle changes that may improve the length and quality of life of their patients. PMID- 26820143 TI - Erratum to: Testosterone stimulates glucose uptake and GLUT4 translocation through LKB1/AMPK signaling in 3T3-L1 adipocytes. PMID- 26820144 TI - The Associations of Youth Physical Activity and Screen Time with Fatness and Fitness: The 2012 NHANES National Youth Fitness Survey. AB - The purpose of the study is to examine the associations of youth physical activity and screen time with weight status and cardiorespiratory fitness in children and adolescents, separately, utilizing a nationally representative sample. A total of 1,113 participants (692 children aged 6-11 yrs; 422 adolescents aged 12-15 yrs) from the 2012 NHANES National Youth Fitness Survey. Participants completed physical activity and screen time questionnaires, and their body mass index and cardiorespiratory fitness (adolescents only) were assessed. Adolescents completed additional physical activity questions to estimate daily MET minutes. Children not meeting the screen time guideline had 1.69 times the odds of being overweight/obese compared to those meeting the screen time guideline, after adjusting for physical activity and other control variables. Among adolescent, screen time was significantly associated with being overweight/obese (odds ratio = 1.82, 95% confidence interval: 1.06-3.15), but the association attenuated toward the borderline of being significant after controlling for physical activity. Being physically active was positively associated with cardiorespiratory fitness, independent of screen time among adolescents. In joint association analysis, children who did not meet physical activity nor screen time guidelines had 2.52 times higher odds of being overweight/obese than children who met both guidelines. Adolescents who did not meet the screen time guideline had significantly higher odds ratio of being overweight/obese regardless of meeting the physical activity guideline. Meeting the physical activity guideline was also associated with cardiorespiratory fitness regardless of meeting the screen time guideline in adolescents. Screen time is a stronger factor than physical activity in predicting weight status in both children and adolescents, and only physical activity is strongly associated with cardiorespiratory fitness in adolescents. PMID- 26820145 TI - Incidence of Co-Infections of HIV, Herpes Simplex Virus Type 2 and Syphilis in a Large Cohort of Men Who Have Sex with Men in Beijing, China. AB - BACKGROUND: The HIV-epidemic among MSM in China has worsened. In this key population, prevalence of HSV-2 and syphilis infection and co-infection with HIV is high. METHODS: A longitudinal study was conducted (n = 962) in Beijing, China, with three overlapping cohorts (n = 857, 757 and 760) consisting of MSM that were free from pairs of infections of concern (i.e. HIV-HSV-2, HIV-syphilis, HSV-2 syphilis) at baseline to estimate incidence of HIV, HSV-2, syphilis, and those of co-infection. RESULTS: The incidence of HIV, HSV-2 and syphilis in the overall cohort was 3.90 (95% CI = 2.37, 5.43), 7.87 (95% CI = 5.74, 10.00) and 6.06 (95% CI = 4.18, 7.94) cases per 100 person-years (PYs), respectively. The incidence of HIV-HSV-2, HIV-Syphilis and HSV-2-Syphilis co-infections was 0.30 (95% CI = 0.29, 0.88), 1.02 (95% CI = 0.13, 2.17) and 1.41 (95% CI: 0.04, 2.78) cases per 100 PYs, respectively, in the three sub-cohorts constructed for this study. CONCLUSIONS: The incidence of HIV, HSV-2 and syphilis was very high and those of their co-infections were relatively high. Such co-infections have negative impacts on the HIV/STI epidemics. Prevention practices need to take such co infections into account. PMID- 26820147 TI - Pharmaceutical Price Schemes in Europe: Time for a 'Continental' One? PMID- 26820148 TI - Apremilast for the Treatment of Moderate to Severe Plaque Psoriasis: A Critique of the Evidence. AB - As part of the National Institute for Health and Care Excellence's (NICE) single technology appraisal (STA) process, apremilast was assessed to determine the clinical and cost effectiveness of its use in the treatment of moderate to severe plaque psoriasis in two patient populations, differentiated by the severity of the patient's Psoriasis Area Severity Index (PASI) score. The Centre for Reviews and Dissemination (CRD) and the Centre for Health Economics (CHE) Technology Appraisal Group at the University of York was commissioned to act as the evidence review group (ERG). This article provides a summary of the company's submission, the ERG report and NICE's subsequent guidance. In the company's initial submission, a sequence of treatments including apremilast was found to be both more effective and cheaper than a comparator sequence without it in both populations considered. However, this result was found to be highly sensitive to a series of assumptions made by the company, primarily reflecting the costs of best supportive care once no further treatments are available, and the source of utility estimates. A re-estimation of the cost effectiveness of apremilast by the ERG suggested that the apremilast sequence in the two populations was more effective, but due to high additional costs was not indicative of a cost effective use of NHS resources. As such, in the final appraisal decision NICE concluded that apremilast was not cost effective in either population. PMID- 26820149 TI - Prospective Investigation of Video Game Use in Children and Subsequent Conduct Disorder and Depression Using Data from the Avon Longitudinal Study of Parents and Children. AB - There is increasing public and scientific concern regarding the long-term behavioural effects of video game use in children, but currently little consensus as to the nature of any such relationships. We investigated the relationship between video game use in children, degree of violence in games, and measures of depression and a 6-level banded measure of conduct disorder. Data from the Avon Longitudinal Study of Parents and Children were used. A 3-level measure of game use at age 8/9 years was developed, taking into account degree of violence based on game genre. Associations with conduct disorder and depression, measured at age 15, were investigated using ordinal logistic regression, adjusted for a number of potential confounders. Shoot-em-up games were associated with conduct disorder bands, and with a binary measure of conduct disorder, although the strength of evidence for these associations was weak. A sensitivity analysis comparing those who play competitive games to those who play shoot-em-ups found weak evidence supporting the hypothesis that it is violence rather than competitiveness that is associated with conduct disorder. However this analysis was underpowered, and we cannot rule out the possibility that increasing levels of competition in games may be just as likely to account for the observed associations as violent content. Overall game exposure as indicated by number of games in a household was not related to conduct disorder, nor was any association found between shoot-em up video game use and depression. PMID- 26820150 TI - Simultaneous and intercontinental tests show synchronism between the local gravimetric tide and the ultra-weak photon emission in seedlings of different plant species. AB - In order to corroborate the hypothesis that variations in the rate of spontaneous ultra-weak photon emission (UPE) from germinating seedlings are related to local variations of the lunisolar tidal force, a series of simultaneous tests was performed using the time courses of UPE collected from three plant species-corn, wheat and sunflower-and also from wheat samples whose grains were transported between continents, from Brazil to The Netherlands and vice versa. All tests which were run in parallel showed coincident inflections within the UPE time courses not only between seedlings of the same species but also between the different species. In most cases, the UPE inflections were synchronised with the turning points in the local gravimetric tidal variation. Statistical tests using the local Pearson correlation verified these coincidences in the two time series. The results therefore support the hypothesis of a relationship between UPE emissions and, in the oscillations, the local gravimetric tide. This applies to both the emissions from seedlings of different species and to the seedlings raised from transported grain samples of the same species. PMID- 26820152 TI - Correction: The Autophagy Receptor TAX1BP1 and the Molecular Motor Myosin VI Are Required for Clearance of Salmonella Typhimurium by Autophagy. AB - [This corrects the article DOI: 10.1371/journal.ppat.1005174.]. PMID- 26820151 TI - The crucial role and regulations of miRNAs in zebrafish development. AB - To comprehend the events during developmental biology, fundamental knowledge about the basic machinery of regulation is a prerequisite. MicroRNA (miRNAs) act as regulators in most of the biological processes and recently, it has been concluded that miRNAs can act as modulatory factors even during developmental process from lower to higher animal. Zebrafish, because of its favorable attributes like tiny size, transparent embryo, and rapid external embryonic development, has gained a preferable status among all other available experimental animal models. Currently, zebrafish is being utilized for experimental studies related to stem cells, regenerative molecular medicine as well drug discovery. Therefore, it is important to understand precisely about the various miRNAs that controls developmental biology of this vertebrate model. In here, we have discussed about the miRNA-controlled zebrafish developmental stages with a special emphasis on different miRNA families such as miR-430, miR-200, and miR-133. Moreover, we have also reviewed the role of various miRNAs during embryonic and vascular development stages of zebrafish. In addition, efforts have been made to summarize the involvement of miRNAs in the development of different body parts such as the brain, eye, heart, muscle, and fin, etc. In each section, we have tried to fulfill the gaps of zebrafish developmental biology with the help of available knowledge of miRNA research. We hope that precise knowledge about the miRNA-regulated developmental stages of zebrafish may further help the researchers to efficiently utilize this vertebrate model for experimental purpose. PMID- 26820153 TI - Thalidomide Improves the Intestinal Mucosal Injury and Suppresses Mesenteric Angiogenesis and Vasodilatation by Down-Regulating Inflammasomes-Related Cascades in Cirrhotic Rats. AB - BACKGROUND AND AIMS: By blocking TNFalpha-related effects, thalidomide not only inhibits hepatic fibrogenesis but improves peripheral vasodilatation and portal hypertension in cirrhotic rats. Nonetheless, the investigation of thalidomide's effects on splanchnic and collateral microcirculation has been limited. Our study explored the roles of intestinal and mesenteric TNFalpha along with inflammasome related pathway in relation to cirrhosis and the splanchnic/collateral microcirculation. METHODS: Using in vivo and in vitro approaches, mechanisms of the effects of thalidomide on intestinal and mesenteric inflammatory, vasodilatory and angiogenic cascades-related abnormalities were explored in cirrhotic rats that had received 1-month thalidomide (C-T) treatment. RESULTS: In cirrhotic rats, high tumor necrosis factor (TNF)alpha, vascular endothelial growth factor (VEGF) and nitric oxide (NO)x levels were associated with the NOD like receptors protein 3 (NLRP3), IL-1beta and caspase-1 inflammasome over expression in splenorenal shunt and mesenteric tissues. The thalidomide-related inhibition of mesenteric and splenorenal shunt inflammasome expression was accompanied by a significantly decreased intestinal mucosal injury and inflammasome immunohistochemical staining expression. Suppression of various angiogenic cascades, namely VEGF-NOS-NO, was paralleled by a decrease in mesenteric angiogenesis as detected by CD31 immunofluorescence staining and by reduced portosystemic shunting (PSS) in C-T rats. The down-regulation of the mesenteric and collateral vasodilatory VEGF-NOS-NO cascades resulted in a correction of vasoconstrictive hypo-responsiveness and in an attenuation of vasodilatory hyper-responsiveness when analyzed by in situ perfusion of the superior mesenteric arterial (SMA) and portosystemic collaterals. There was also a decrease in SMA blood flow and an increase in SMA resistance in the C-T rats. Additionally, acute incubation with thalidomide abolished TNFalpha-augmented VEGF mediated migration of and tube formation of human umbilical vein endothelial cells, which was accompanied by corresponding changes in inflammatory and angiogenic substances release. CONCLUSIONS: The suppression of inflammasome over expression by chronic thalidomide treatment ameliorates inflammatory, angiogenic and vasodilatory cascades-related pathogenic changes in the splanchnic and collateral microcirculation of cirrhotic rats. Thalidomide seems to be a promising agent that might bring about beneficial changes to the disarrangements of peripheral, hepatic, splanchnic and collateral systems in cirrhosis. PMID- 26820154 TI - Sexual Dysfunction in Heroin Dependents: A Comparison between Methadone and Buprenorphine Maintenance Treatment. AB - INTRODUCTION: Methadone has long been regarded as an effective treatment for opioid dependence. However, many patients discontinue maintenance therapy because of its side effects, with one of the most common being sexual dysfunction. Buprenorphine is a proven alternative to methadone. This study aimed to investigate sexual dysfunction in opioid-dependent men on buprenorphine maintenance treatment (BMT) and methadone maintenance treatment (MMT). The secondary aim was to investigate the correlation between sexual dysfunction and the quality of life in these patients. METHODS: Two hundred thirty-eight men participated in this cross-sectional study. Four questionnaires were used, the Mini International Neuropsychiatric Interview, Opiate Treatment Index, Malay version of the International Index of Erectile Function 15 (Mal-IIEF-15), and World Health Organization Quality of Life-BREF Scale. Multivariate analysis of covariance was used to examine the relationship between MMT and BMT and the Mal IIEF 15 scores while controlling for all the possible confounders. RESULTS: The study population consisted of 171 patients (71.8%) on MMT and 67 (28.2%) on BMT. Patients in the MMT group who had a sexual partner scored significantly lower in the sexual desire domain (p < 0.012) and overall satisfaction (p = 0.043) domain compared with their counterparts in the BMT group. Similarly, patients in the MMT group without a sexual partner scored significantly lower in the orgasmic function domain (p = 0.008) compared with those in the BMT group without a partner. Intercourse satisfaction (p = 0.026) and overall satisfaction (p = 0.039) were significantly associated with the social relationships domain after adjusting for significantly correlated sociodemographic variables. CONCLUSIONS: Sexual functioning is critical for improving the quality of life in patients in an opioid rehabilitation program. Our study showed that buprenorphine causes less sexual dysfunction than methadone. Thus, clinicians may consider the former when treating heroin dependents who have concerns about sexual function. PMID- 26820156 TI - Proteomics of Secretory-Stage and Maturation-Stage Enamel of Genetically Distinct Mice. AB - The mechanisms by which excessive ingestion of fluoride (F) during amelogenesis leads to dental fluorosis (DF) are still not precisely known. Inbred strains of mice vary in their susceptibility to develop DF, and therefore permit the investigation of underlying molecular events influencing DF severity. We employed a proteomic approach to characterize and evaluate changes in protein expression from secretory-stage and maturation-stage enamel in 2 strains of mice with different susceptibilities to DF (A/J, i.e. 'susceptible' and 129P3/J, i.e. 'resistant'). Weanling male and female susceptible and resistant mice fed a low-F diet were divided into 2 F-water treatment groups. They received water containing 0 (control) or 50 mg F/l for 6 weeks. Plasma and incisor enamel was analyzed for F content. For proteomic analysis, the enamel proteins extracted for each group were separated by 2-dimensional electrophoresis and subsequently characterized by liquid-chromatography electrospray-ionization quadrupole time-of-flight mass spectrometry. F data were analyzed by 2-way ANOVA and Bonferroni's test (p < 0.05). Resistant mice had significantly higher plasma and enamel F concentrations when compared with susceptible mice in the F-treated groups. The proteomic results for mice treated with 0 mg F/l revealed that during the secretory stage, resistant mice had a higher abundance of proteins than their susceptible counterparts, but this was reversed during the maturation stage. Treatment with F greatly increased the number of protein spots detected in both stages. Many proteins not previously described in enamel (e.g. type 1 collagen) as well as some uncharacterized proteins were identified. Our findings reveal new insights regarding amelogenesis and how genetic background and F affect this process. PMID- 26820155 TI - Functional Investigation of a Non-coding Variant Associated with Adolescent Idiopathic Scoliosis in Zebrafish: Elevated Expression of the Ladybird Homeobox Gene Causes Body Axis Deformation. AB - Previously, we identified an adolescent idiopathic scoliosis susceptibility locus near human ladybird homeobox 1 (LBX1) and FLJ41350 by a genome-wide association study. Here, we characterized the associated non-coding variant and investigated the function of these genes. A chromosome conformation capture assay revealed that the genome region with the most significantly associated single nucleotide polymorphism (rs11190870) physically interacted with the promoter region of LBX1 FLJ41350. The promoter in the direction of LBX1, combined with a 590-bp region including rs11190870, had higher transcriptional activity with the risk allele than that with the non-risk allele in HEK 293T cells. The ubiquitous overexpression of human LBX1 or either of the zebrafish lbx genes (lbx1a, lbx1b, and lbx2), but not FLJ41350, in zebrafish embryos caused body curvature followed by death prior to vertebral column formation. Such body axis deformation was not observed in transcription activator-like effector nucleases mediated knockout zebrafish of lbx1b or lbx2. Mosaic expression of lbx1b driven by the GATA2 minimal promoter and the lbx1b enhancer in zebrafish significantly alleviated the embryonic lethal phenotype to allow observation of the later onset of the spinal curvature with or without vertebral malformation. Deformation of the embryonic body axis by lbx1b overexpression was associated with defects in convergent extension, which is a component of the main axis-elongation machinery in gastrulating embryos. In embryos overexpressing lbx1b, wnt5b, a ligand of the non canonical Wnt/planar cell polarity (PCP) pathway, was significantly downregulated. Injection of mRNA for wnt5b or RhoA, a key downstream effector of Wnt/PCP signaling, rescued the defective convergent extension phenotype and attenuated the lbx1b-induced curvature of the body axis. Thus, our study presents a novel pathological feature of LBX1 and its zebrafish homologs in body axis deformation at various stages of embryonic and subsequent growth in zebrafish. PMID- 26820157 TI - [Lymphatic malformations in the head and neck area]. AB - Lymphatic malformations are congenital malformations of the lymphatic system. They are mainly located in the head and neck area, and grow proportional to the patients' body growth. Depending on the morphology, it can be distinguished between macrocystic, microcystic and mixed lymphatic malformations. Due to their infiltrative growth, microcystic lymphatic malformations are particularly difficult to treat. Therapeutic approaches include conventional surgical resection, laser therapy, sclerotherapy and systemic drug therapies. PMID- 26820159 TI - Correction to "Electrochemical Formation of an Ultrathin Electroactive Film from 1,10-Phenanthroline on a Glassy Carbon Electrode in Acidic Electrolyte". PMID- 26820160 TI - Electrical Properties of Synthesized Large-Area MoS2 Field-Effect Transistors Fabricated with Inkjet-Printed Contacts. AB - We report the electrical properties of synthesized large-area monolayer molybdenum disulfide (MoS2) field-effect transistors (FETs) with low-cost inkjet printed Ag electrodes. The monolayer MoS2 film was grown by a chemical vapor deposition (CVD) method, and the top-contact Ag source/drain electrodes (S/D) were deposited onto the films using a low-cost drop-on-demand inkjet-printing process without any masks and surface treatments. The electrical characteristics of FETs were comparable to those fabricated by conventional deposition methods such as photo- or electron beam lithography. The contact properties between the S/D and the semiconductor layer were also evaluated using the Y-function method and an analysis of the output characteristic at the low drain voltage regimes. Furthermore, the electrical instability under positive gate-bias stress was studied to investigate the charge-trapping mechanism of the FETs. CVD-grown large area monolayer MoS2 FETs with inkjet-printed contacts may represent an attractive approach for realizing large-area and low-cost thin-film electronics. PMID- 26820158 TI - Increased endothelial microparticles and oxidative stress at extreme altitude. AB - PURPOSE: Hypoxia and oxidative stress affect endothelial function. Endothelial microparticles (MP) are established measures of endothelial dysfunction and influence vascular reactivity. To evaluate the effects of hypoxia and antioxidant supplementation on endothelial MP profiles, a double-blind, placebo-controlled trial, during a high altitude expedition was performed. METHODS: 29 participants were randomly assigned to a treatment group (n = 14), receiving vitamin E, C, A, and N-acetylcysteine daily, and a control group (n = 15), receiving placebo. Blood samples were obtained at 490 m (baseline), 3530, 4590, and 6210 m. A sensitive tandem mass spectrometry method was used to measure 8-iso-prostaglandin F2alpha and hydroxyoctadecadienoic acids as markers of oxidative stress. Assessment of MP profiles including endothelial activation markers (CD62+MP and CD144+MP) and cell apoptosis markers (phosphatidylserine+MP and CD31+MP) was performed using a standardized flow cytometry-based protocol. RESULTS: 15 subjects reached all altitudes and were included in the final analysis. Oxidative stress increased significantly at altitude. No statistically significant changes were observed comparing baseline to altitude measurements of phosphatidylserine expressing MP (p = 0.1718) and CD31+MP (p = 0.1305). Compared to baseline measurements, a significant increase in CD62+MP (p = 0.0079) and of CD144+MP was detected (p = 0.0315) at high altitudes. No significant difference in any MP level or oxidative stress markers were found between the treatment and the control group. CONCLUSION: Hypobaric hypoxia is associated with increased oxidative stress and induces a significant increase in CD62+ and CD144+MP, whereas phosphatidylserine+MP and CD31+MP remain unchanged. This indicates that endothelial activation rather than an apoptosis is the primary factor of hypoxia induced endothelial dysfunction. PMID- 26820161 TI - HistoMosaic Detecting KRAS G12V Mutation Across Colorectal Cancer Tissue Slices through in Situ PCR. AB - We report on HistoMosaic, a novel technique for genetic analysis of formalin fixed, paraffin-embedded tissue slices. It combines microfluidic compartmentalization, in situ allele-specific PCR, and fluorescence microscopy. The experimental proof of principle was achieved by in situ detection of KRAS G12V mutation in colorectal cancer tissues and is presented herein. HistoMosaic offers the ability to detect mutations over the entire tissue slide simultaneously, rapidly, economically, and without selection bias, while coregistering the genetic information with the preserved morphological information. Thus, HistoMosaic has wide applicability in basic science as a tool to map genetic heterogeneity. It is also a platform to build companion diagnostics for targeted therapies in oncology, to help ensure that the right drug is given to the right patient, thereby saving healthcare resources and improving patient outcomes. PMID- 26820162 TI - Toward a Physically Motivated Force Field: Hydrogen Bond Directionality from a Symmetry-Adapted Perturbation Theory Perspective. AB - It is argued here that the functional forms adopted in almost all popular force fields are too restrictive to allow for accurate and physics-based parametrization. Some important modifications are suggested based on symmetry adapted intermolecular perturbation theory, which directly separates the intermolecular interaction energy into four physically interpretable components: electrostatics, exchange-repulsion, dispersion, and induction. The exact electrostatic energy is approximated as a sum of the short-range contribution (due to charge density penetration effects), included explicitly, and the long range part (via distributed atomic multipoles), whereas the induction energy is evaluated by means of the distributed induced damped point dipole model. The dispersion energy is fitted to a simple analytical function and the exchange repulsion contribution is approximated by the overlap of the valence-only electron charge densities of monomers. The water dimer is used to illustrate the approach and to discuss its potential and possible improvements. Analysis of the four main contributions to the binding energy allows for a deeper understanding of the hydrogen bond directionality. It is found that a notorious geometrical preference in the water dimer results mainly from large polarization contributions, including induction and dispersion. PMID- 26820163 TI - Zika Virus Spreads to New Areas - Region of the Americas, May 2015-January 2016. AB - Zika virus is a mosquito-borne flavivirus that was first identified in Uganda in 1947 (1). Before 2007, only sporadic human disease cases were reported from countries in Africa and Asia. In 2007, the first documented outbreak of Zika virus disease was reported in Yap State, Federated States of Micronesia; 73% of the population aged >=3 years is estimated to have been infected (2). Subsequent outbreaks occurred in Southeast Asia and the Western Pacific (3). In May 2015, the World Health Organization reported the first local transmission of Zika virus in the Region of the Americas (Americas), with autochthonous cases identified in Brazil (4). In December, the Ministry of Health estimated that 440,000-1,300,000 suspected cases of Zika virus disease had occurred in Brazil in 2015 (5). By January 20, 2016, locally-transmitted cases had been reported to the Pan American Health Organization from Puerto Rico and 19 other countries or territories in the Americas* (Figure) (6). Further spread to other countries in the region is being monitored closely. PMID- 26820164 TI - Tandem Radical Fluoroalkylation-Cyclization: Synthesis of Tetrafluoro Imidazopyridines. AB - A copper-catalyzed fluoroalkylation-cyclization sequence of alkenes and alkynes enables the synthesis of fluorinated tetra- and dihydroimidazopyridines in moderate to excellent yields within 1 h at 70 degrees C. This reaction, which is carried out using copper(I) acetate as the catalyst, makes use of a new class of functionalized tetrafluoroethyl reagents based on a hypervalent iodine scaffold. PMID- 26820165 TI - One-Pot Fabrication of Mesoporous Core-Shell Au@PtNi Ternary Metallic Nanoparticles and Their Enhanced Efficiency for Oxygen Reduction Reaction. AB - Currently, Pt-based nanomaterials with tailorable shapes, structures, and morphologies are the most popular electrocatalysts for oxygen reduction reaction, which is a significant cathode reaction in fuel cells for renewable energy applications. We have successfully synthesized mesoporous core-shell Au@PtNi ternary metallic nanoparticles through a one-pot reduction method for cathodic materials used as oxygen reduction reaction catalysts. The as-synthesized nanoparticles exhibited superior catalytic activities and long-term stabilities compared with mesoporous core-shell Au@Pt nanoparticles and commercial Pt/C. The unique mesoporous core-shell structures as well as the alloy shells enable the enhanced electrochemical oxygen reduction reaction performances of the Pt-based materials via the electronic effect and geometric effect, holding great promise in fuel cell application. PMID- 26820166 TI - Worrying about the future: An episodic specificity induction impacts problem solving, reappraisal, and well-being. AB - Previous research has demonstrated that an episodic specificity induction--brief training in recollecting details of a recent experience--enhances performance on various subsequent tasks thought to draw upon episodic memory processes. Existing work has also shown that mental simulation can be beneficial for emotion regulation and coping with stressors. Here we focus on understanding how episodic detail can affect problem solving, reappraisal, and psychological well-being regarding worrisome future events. In Experiment 1, an episodic specificity induction significantly improved participants' performance on a subsequent means end problem solving task (i.e., more relevant steps) and an episodic reappraisal task (i.e., more episodic details) involving personally worrisome future events compared with a control induction not focused on episodic specificity. Imagining constructive behaviors with increased episodic detail via the specificity induction was also related to significantly larger decreases in anxiety, perceived likelihood of a bad outcome, and perceived difficulty to cope with a bad outcome, as well as larger increases in perceived likelihood of a good outcome and indicated use of active coping behaviors compared with the control. In Experiment 2, we extended these findings using a more stringent control induction, and found preliminary evidence that the specificity induction was related to an increase in positive affect and decrease in negative affect compared with the control. Our findings support the idea that episodic memory processes are involved in means-end problem solving and episodic reappraisal, and that increasing the episodic specificity of imagining constructive behaviors regarding worrisome events may be related to improved psychological well-being. PMID- 26820167 TI - Transcriptomic study of high-glucose effects on human skin fibroblast cells. AB - Skin ulcers are a common complication of diabetes mellitus (DM). Fibroblasts are located within the dermis of skin tissue and can be damaged by diabetes. However, the underlying mechanism of how DM affects fibroblasts remains elusive. To understand the effects of DM on fibroblasts, the current study mimicked DM by high-glucose (HG) supplementation in the culture medium of human foreskin primary fibroblast cells, and the analysis of transcriptomic changes was conducted. RNA sequencing-based transcriptome analysis identified that, upon HG stress, 463 genes were upregulated and 351 genes downregulated (>1.5-fold changes; P<0.05). These altered genes were distributed into 20 different pathways. In addition, gene ontology (GO) analysis indicated that 31 GO terms were enriched. Among the pathways identified, nuclear factor kappaB (NF-kappaB) pathway genes were highly expressed, and the addition of Bay11-7082, a typical NF-kappaB signaling inhibitor, blocked the previously observed alterations in plasminogen activator inhibitor 1 (PAI1), an inflammation marker and frizzled class receptor 8 (FZD8), a Wnt signaling gene, expression that resulted from HG stress. Furthermore, an inhibitor of Wnt signaling diminished the role of Bay11-7082 in the regulation of PAI1 expression under HG conditions, suggesting that Wnt signaling may function downstream of the NF-kappaB pathway to protect fibroblast cells from HG stress. To the best of our knowledge, the current study is the first analysis of transcriptomic responses under HG stress in human fibroblasts. The data provided here may aid the understanding of the molecular mechanisms by which fibroblast cells are damaged in the skin of patients with DM. PMID- 26820168 TI - Plasma disposition and faecal excretion of eprinomectin following topical and subcutaneous administration in non-lactating dairy cattle. AB - AIMS: To investigate the plasma disposition and faecal excretion of eprinomectin (EPM) in non-lactating dairy cattle following topical and S/C administration. METHODS: Holstein dairy cows, 3.5-5 years-old, were selected 20-25 days after being dried off and were randomly allocated to receive EPM either topically (n=5) or S/C (n=5) at dose rates of 0.5 and 0.2 mg/kg bodyweight, respectively. Heparinised blood and faecal samples were collected at various times between 1 hour and 30 days after treatment, and were analysed for concentrations of EPM using high performance liquid chromatography with a fluorescence detector. RESULTS: The maximum concentration of EPM in plasma (Cmax) and the time to reach Cmax were both greater after S/C administration (59.70 (SD 12.90) ng/mL and 1.30 (SD 0.27) days, respectively) than after topical administration (20.73 (SD 4.04) ng/mL and 4.40 (SD 0.89) days, respectively) (p<0.001). In addition, S/C administration resulted in greater plasma availability (area under the curve; AUC), and a shorter terminal half-life and mean residence time (295.9 (SD 61.47) ng.day/mL; 2.95 (SD 0.74) days and 4.69 (SD 1.01) days, respectively) compared with topical administration (168.2 (SD15.67) ng.day/mL; 4.63 (SD 0.32) days, and 8.23 (SD 0.57) days, respectively) (p<0.01). EPM was detected in faeces between 0.80 (SD 0.45) and 13.6 (SD 4.16) days following S/C administration, and between 1 (SD 0.5) and 20.0 (SD 3.54) days following topical administration. Subcutaneous administration resulted in greater faecal excretion than topical administration, expressed as AUC adjusted for dose (1188.9 (SD 491.64) vs. 311.5 (SD 46.90) ng.day/g; p<0.05). Maximum concentration in faeces was also higher following S/C than topical administration (223.0 (SD 63.96) vs. 99.47 (SD 43.24) ng/g; p<0.01). CONCLUSIONS: Subcutaneous administration of EPM generated higher plasma concentrations and greater plasma availability compared with topical administration in non-lactating cattle. Although the S/C route provides higher faecal concentrations, the longer faecal persistence of EPM following topical administration may result in more persistent efficacy preventing establishment of incoming nematode larvae in cattle. PMID- 26820169 TI - Combination effect of super pulsed carbon dioxide laser and photodynamic therapy for recalcitrant facial flat warts: A preliminary study. PMID- 26820170 TI - Tyrosine receptor kinase B silencing inhibits anoikis-resistance and improves anticancer efficiency of sorafenib in human renal cancer cells. AB - Renal cell carcinoma (RCC) is the most common solid neoplasm of adult kidney, and the major treatment for metastatic RCC (mRCC) is molecular targeted therapy. Sorafenib, as a multi-targeted tyrosine kinase inhibitor (TKI), has significantly improved clinical outcomes of mRCC patients. However, complete or long-term remissions are rarely achieved due to intolerance to dose-related adverse effects. It is therefore, necessary to explore novel target molecules for treatment or to enhance the therapeutic efficiency of present TKI for mRCC treatment. Anoikis is a specific type of apoptosis that plays a vital physiological role in regulating tissue homoeostasis. Anoikis-resistance is of critical importance for metastasis of various human cancers including mRCC. However, the precise mechanisms on anoikis-resistance in mRCC are still unclear. Tyrosine receptor kinase B (TrkB) belongs to the Trk family of neurotrophin receptors. Previous investigations have implied that activation or overexpression of TrkB promoted proliferation, survival, angiogenesis, anoikis-resistance and metastasis in human cancers. Yet, the correlation between TrkB and anoikis resistance in mRCC has rarely been reported. The aim of the present study was to explore the impact of TrkB on anoikis-resistance and targeted therapy in mRCC. Our data revealed that anoikis-resistant ACHN cells presented with tolerance to detachment-induced apoptosis, excessive proliferation and aggressive invasion, accompanied by upregulation of TrkB expression in contrast to parental cells. Furthermore, TrkB silencing caused apoptosis, inhibited proliferation, retarded invasion as well as improved anticancer efficiency of sorafenib in anoikis resistant ACHN cells through inactivation of PI3K/Akt and MEK/ERK pathways. Our data may offer a novel potential therapeutic strategy for mRCC. PMID- 26820171 TI - A case of butane hash oil (marijuana wax)-induced psychosis. AB - BACKGROUND: Marijuana is one of the most widely used controlled substances in the United States. Despite extensive research on smoked marijuana, little is known regarding the potential psychotropic effects of marijuana "wax," a high-potency form of marijuana that is gaining in popularity. CASE: The authors present a case of "Mr. B," a 34-year-old veteran who presented with profound psychosis in the setting of recent initiation of heavy, daily marijuana wax use. He exhibited incoherent speech and odd behaviors and appeared to be in a dream-like state with perseverating thoughts about his combat experience. His condition persisted despite treatment with risperidone 4 mg twice a day (BID), but improved dramatically on day 8 of hospitalization with the return of baseline mental function. Following discharge, Mr. B discontinued all marijuana use and did not exhibit the return of any psychotic symptoms. DISCUSSION: This study highlights the need for future research regarding the potential medical and psychiatric effects of new, high-potency forms of marijuana. Could cannabis have a dose dependent impact on psychosis? What other potential psychiatric effects could emerge heretofore unseen in lower potency formulations? Given the recent legalization of marijuana, these questions merit timely exploration. PMID- 26820172 TI - Acutifoliside, a novel benzoic acid glycoside from Salix acutifolia. AB - Ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) profiling of a polar solvent extract of juvenile stem tissue of Salix acutifolia Willd. identified a range of phenolic metabolites. Salicortin, 1, a well-known salicinoid, was the major compound present and the study identified young stem tissue of this species as a potential source of this compound for future studies. Three further known metabolites (salicin 2, catechin 3 and tremuloidin 4) were also present. The UHPLC-MS analysis also revealed the presence of a further, less polar, unknown compound, which was isolated via HPLC peak collection. The structure was elucidated by high-resolution mass spectroscopic analysis, 1- and 2 D NMR analysis and chemical derivatisation and was shown to be a novel benzoic acid glycoside 5, which we have named as acutifoliside. PMID- 26820173 TI - Weight loss methods and changes in eating habits among successful weight losers. AB - BACKGROUND: Changes in several lifestyle related factors are required for successful long-term weight loss. Identification of these factors is of major importance from a public health point of view. METHODS/SUBJECTS: This study was based upon findings from the Finnish Weight Control Registry (FWCR), a web-based registry. In total, 316 people were recruited and 184 met the study inclusion criteria. The aims of this study were to assess means and typical changes in eating habits associated with successful long-term weight loss. RESULTS: Half of the participants (48%) reported that they lost weight slowly primarily with dietary changes. Self-weighing frequency was high, 92% was weighing themselves at least once a week during the weight loss phase, and 75% during the maintenance phase. Dietary aspects associated with successful weight loss and weight maintenance included an increase in intake of vegetables, a reduction in frequency of eating candies and fast food, regular meal frequency and application of the Plate model. CONCLUSIONS: Both slow and fast weight loss may lead to successful long-term results and weight maintenance. A decrease in energy intake was achieved by reducing intake of energy-dense food, applying the Plate model and by regular meal frequency. Key messages Successful long-term weight loss is associated with a reduction in intake of energy-dense food. A more regular meal frequency and a high frequency of self-weighing seem to be helpful. PMID- 26820174 TI - Suicide gene-modified killer cells as an allogeneic alternative to autologous cytokine-induced killer cell immunotherapy of hepatocellular carcinoma. AB - Adoptive immunotherapy using autologous cytokine-induced killer (CIK) cells reduces the recurrence rate of hepatocellular carcinoma (HCC) in association with transarterial chemoembolization or radiofrequency. However, a large-scale development of this immunotherapy remains difficult to consider in an autologous setting, considering the logistical hurdles associated with the production of this cell therapy product. A previous study has provided the in vitro and in vivo proof-of-concept that allogeneic suicide gene-modified killer cells (aSGMKCs) from healthy blood donors (a cell therapy product previously demonstrated to provide anti-leukemic effects to patients receiving allogeneic hematopoietic transplantation) may exert a potent anti-tumor effect towards HCC. Therefore, the development of a bank of 'ready-for-use' aSGMKCs was proposed as an approach allowing for the development of immunotherapies that are more convenient and on a broader scale than that of autologous therapies. In the present study, aSGMKCs were compared with CIK cells generated according to three different protocols. Similar to CIK cells, the cytotoxic activity of aSGMKCs toward the Huh-7 HCC cell line was mediated by tumor necrosis factor-related apoptosis-inducing ligand, tumor necrosis factor-alpha and interferon-gamma. Furthermore, the frequency of natural killer (NK), NK-like T and T cells, and their in vitro and in vivo cytotoxicity activities were similar between aSGMKCs and CIK cells. Thus, the present study demonstrated that aSGMKCs are similar to CIK cells, further suggesting the possibility for future use of aSGMKCs in the treatment of solid tumors, including HCC. PMID- 26820175 TI - Knife-assisted snare resection: a novel technique for resection of scarred polyps in the colon. AB - BACKGROUND AND STUDY AIMS: There have been significant advances in the management of complex colorectal polyps. Previous failed resection or polyp recurrence is associated with significant fibrosis, making endoscopic resection extremely challenging; the traditional approach to these lesions is surgery. The aim of this study was to evaluate the efficacy of a novel, knife-assisted snare resection (KAR) technique in the resection of scarred colonic polyps. PATIENTS AND METHODS: This was a prospective cohort study of patients, in whom the KAR technique was used to resect scarred colonic polyps > 2 cm in size. Patients had previously undergone endoscopic mucosal resection (EMR) and developed recurrence, or EMR had been attempted but was aborted as a result of technical difficulty. RESULTS: A total of 42 patients underwent KAR of large (median 40 mm) scarred polyps. Surgery for benign disease was avoided in 38 of 41 patients (93 %). No life-threatening complications occurred. Recurrence was seen in six patients (16 %), five of whom underwent further endoscopic resection. The overall cure rate for KAR in complex scarred colonic polyps was 90 %. CONCLUSIONS: KAR of scarred colonic polyps by an expert endoscopist was an effective and safe technique with low recurrence rates. PMID- 26820176 TI - 1,2,3-Triazolium-Based Poly(2,6-Dimethyl Phenylene Oxide) Copolymers as Anion Exchange Membranes. AB - Anion exchange membranes (AEMs) based on 1,2,3-triazolium (TAM) were prepared from commercial poly(2,6-dimethyl phenylene oxide) (PPO) via "click chemistry" and subsequent N-alkylation. Flexible and tough membranes with various ion exchange capacities (IECs) were obtained by casting the polymers from NMP solutions. Although the resulting TAM-functionalized PPOs (PPO-TAM) membranes exhibited incomplete ion exchange in 1 M NaOH or NaHCO3 for 24 h even at elevated temperature, the highest hydroxide conductivities of the membranes were above 20 mS/cm at room temperature, which is comparable to many reported AEMs. Alkaline stability tests indicate that the PPO-TAM membranes showed a better alkaline stability than that of membranes containing imidazolium groups in 1 M NaOH at 80 degrees C, but still require further improvements in long-term stability for alkaline fuel cell application. An investigation of alkaline stability of model compounds demonstrated the instability of TAM cations under alkaline conditions could contribute to the deprotonation of benzylic methylene, C4 and C5 position on the triazolium ring. These results suggests that the alkaline stability of 1,2,3-triazolium cation could be improved by the introduction of substituents at the C4, C5 positions and benzylic methylene, and also provide insight and directions for organic cation designs for AEM application by the facile synthetic strategy of "click chemistry". PMID- 26820178 TI - E-waste: the growing global problem and next steps. AB - In many low- and middle-income countries, handling and disposal of discarded electrical or electronic equipment (EEE) is frequently unregulated. e-Waste contains hazardous constituents such as lead, mercury, and chromium, certain chemicals in plastics, and flame retardants. There is increasing concern about health effects related to contamination in air, soil, and water for people working and living at or near informal e-waste processing sites, especially to the most vulnerable populations, pregnant women and children. The observed adverse health effects and increasing number of e-waste sites make protecting human health and the environment from e-waste contamination an expanding challenge. Through international cooperation, awareness can be elevated about the harm that e-waste processing poses to human health. Here we discuss how international researchers, public health practitioners, and policymakers can employ solutions to reduce e-waste exposures. PMID- 26820177 TI - Connecting mercury science to policy: from sources to seafood. AB - Mercury (Hg) is a global contaminant whose presence in the biosphere has been increased by human activity, particularly coal burning/energy production, mining, especially artisanal scale gold mining, and other industrial activities. Mercury input to the surface ocean has doubled over the past century leading governments and organizations to take actions to protect humans from the harmful effects of this toxic element. Recently, the UN Environmental Program led 128 countries to negotiate and sign a legally binding agreement, the 2013 Minimata Convention, to control Hg emissions and releases to land and water globally. In an effort to communicate science to this emerging international policy, the Dartmouth Superfund Research Program formed the Coastal and Marine Mercury Ecosystem Research Collaborative (C-MERC) in 2010 that brought together more than 70 scientists and policy experts to analyze and synthesize the science on Hg pollution in the marine environment from Hg sources to MeHg in seafood. The synthesis of the science revealed that the sources and inputs of Hg and their pathways to human exposure are largely determined by ecosystem spatial scales and that these spatial scales determine the organizational level of policies. The paper summarizes the four major findings of the report. PMID- 26820179 TI - Domestic incense use and lung cancer in Asia: a review. AB - While there is strong evidence for the association between household air pollution and lung cancer among non-smoking women, the association between domestic incense use and lung cancer risk has been inconsistent. We conducted a systematic review of PubMed articles authored between 1969 and August 25, 2015 before performing a manual review of each study, and found a total of seven published studies on this topic. Most of the studies are case-control in design and did not further stratify by sex and smoking status. Of the seven studies, three reported positive associations, three reported null associations and one study found a negative association between incense use and lung cancer. Only one study reported estimates for non-smoking women. Future studies should be larger in sample size, stratify by both sex and smoking status in their analyses, and collect more detailed information on incense use in order to facilitate the understanding of the association between domestic incense use and lung cancer risk among non-smoking women in Asia. PMID- 26820180 TI - Reconciling PM10 analyses by different sampling methods for Iron King Mine tailings dust. AB - The overall project objective at the Iron King Mine Superfund site is to determine the level and potential risk associated with heavy metal exposure of the proximate population emanating from the site's tailings pile. To provide sufficient size-fractioned dust for multi-discipline research studies, a dust generator was built and is now being used to generate size-fractioned dust samples for toxicity investigations using in vitro cell culture and animal exposure experiments as well as studies on geochemical characterization and bioassay solubilization with simulated lung and gastric fluid extractants. The objective of this study is to provide a robust method for source identification by comparing the tailing sample produced by dust generator and that collected by MOUDI sampler. As and Pb concentrations of the PM10 fraction in the MOUDI sample were much lower than in tailing samples produced by the dust generator, indicating a dilution of Iron King tailing dust by dust from other sources. For source apportionment purposes, single element concentration method was used based on the assumption that the PM10 fraction comes from a background source plus the Iron King tailing source. The method's conclusion that nearly all arsenic and lead in the PM10 dust fraction originated from the tailings substantiates our previous Pb and Sr isotope study conclusion. As and Pb showed a similar mass fraction from Iron King for all sites suggesting that As and Pb have the same major emission source. Further validation of this simple source apportionment method is needed based on other elements and sites. PMID- 26820181 TI - Life in the cold: links between mammalian hibernation and longevity. AB - The biological process of aging is the primary determinant of lifespan, but the factors that influence the rate of aging are not yet clearly understood and remain a challenging question. Mammals are characterized by >100-fold differences in maximal lifespan, influenced by relative variances in body mass and metabolic rate. Recent discoveries have identified long-lived mammalian species that deviate from the expected longevity quotient. A commonality among many long-lived species is the capacity to undergo metabolic rate depression, effectively re programming normal metabolism in response to extreme environmental stress and enter states of torpor or hibernation. This stress tolerant phenotype often involves a reduction in overall metabolic rate to just 1-5% of the normal basal rate as well as activation of cytoprotective responses. At the cellular level, major energy savings are achieved via coordinated suppression of many ATP expensive cell functions; e.g. global rates of protein synthesis are strongly reduced via inhibition of the insulin signaling axis. At the same time, various studies have shown activation of stress survival signaling during hibernation including up-regulation of protein chaperones, increased antioxidant defenses, and transcriptional activation of pro-survival signaling such as the FOXO and p53 pathways. Many similarities and parallels exist between hibernation phenotypes and different long-lived models, e.g. signal transduction pathways found to be commonly regulated during hibernation are also known to induce lifespan extension in animals such as Drosophila melanogaster and Caenorhabditis elegans. In this review, we highlight some of the molecular mechanisms that promote longevity in classic aging models C. elegans, Drosophila, and mice, while providing a comparative analysis to how they are regulated during mammalian hibernation. PMID- 26820182 TI - Comorbidities Matter: A Call to Improve Care for Hospitalized Patients with Alzheimer's and Parkinson's Disease. PMID- 26820185 TI - Evidence-Based Practice Guideline: Changing the Practice of Physical Restraint Use in Acute Care. AB - Physical restraints continue to be used in acute care settings, despite the challenges and calls to reduce this practice. The current guideline on restraint use is updated with evidence that includes critical care settings and issues related to restraint use in acute care units. Nurses play a significant role in the use of restraints. Factors such as nurse's knowledge and patient characteristics combined with the culture and resources in health care facilities influence the practice of physical restraint use. Nurses can identify patients at high risk for restraint use; assess the potential causes of unsafe behaviors; and target interventions in the areas of physiological, psychological, and environmental approaches to address those unsafe behaviors. Members of the interdisciplinary team can provide additional consultation, and institutions can provide resources and education and implement monitoring processes and quality improvement practices to help reduce the practice of physical restraint use. [Journal of Gerontological Nursing, 42(2), 17-26.]. PMID- 26820187 TI - Flaming Mame. PMID- 26820189 TI - Synthesis of polysubstituted 1,2-dihydroquinolines and indoles via cascade reactions of arylamines and propargylic alcohols catalyzed by FeCl3.6H2O. AB - An efficient, environmentally friendly and high-yielding route from inexpensive starting materials to 1,2-dihydroquinolines has been developed. This procedure proceeded via a cascade Friedel-Crafts-type reaction and 6-endo-trig hydroamination under the catalysis of FeCl3.6H2O, involving the formation of two new sigma (C-C and C-N) bonds in a single operation for the construction of a 1,2 dihydroquinoline skeleton in good to excellent yields. PMID- 26820188 TI - Multivariate analysis of the population representativeness of related clinical studies. AB - OBJECTIVE: To develop a multivariate method for quantifying the population representativeness across related clinical studies and a computational method for identifying and characterizing underrepresented subgroups in clinical studies. METHODS: We extended a published metric named Generalizability Index for Study Traits (GIST) to include multiple study traits for quantifying the population representativeness of a set of related studies by assuming the independence and equal importance among all study traits. On this basis, we compared the effectiveness of GIST and multivariate GIST (mGIST) qualitatively. We further developed an algorithm called "Multivariate Underrepresented Subgroup Identification" (MAGIC) for constructing optimal combinations of distinct value intervals of multiple traits to define underrepresented subgroups in a set of related studies. Using Type 2 diabetes mellitus (T2DM) as an example, we identified and extracted frequently used quantitative eligibility criteria variables in a set of clinical studies. We profiled the T2DM target population using the National Health and Nutrition Examination Survey (NHANES) data. RESULTS: According to the mGIST scores for four example variables, i.e., age, HbA1c, BMI, and gender, the included observational T2DM studies had superior population representativeness than the interventional T2DM studies. For the interventional T2DM studies, Phase I trials had better population representativeness than Phase III trials. People at least 65years old with HbA1c value between 5.7% and 7.2% were particularly underrepresented in the included T2DM trials. These results confirmed well-known knowledge and demonstrated the effectiveness of our methods in population representativeness assessment. CONCLUSIONS: mGIST is effective at quantifying population representativeness of related clinical studies using multiple numeric study traits. MAGIC identifies underrepresented subgroups in clinical studies. Both data-driven methods can be used to improve the transparency of design bias in participation selection at the research community level. PMID- 26820190 TI - Food quality and authenticity screening via easy ambient sonic-spray ionization mass spectrometry. AB - This review is the first to summarize a decade of studies testing the use of easy ambient sonic-spray ionization mass spectrometry (EASI-MS) and its several sister techniques, Venturi (V-EASI), thermal imprinting (TI-EASI) and Spartan (S-EASI) mass spectrometry in food quality control and authentication. Since minimal or no sample preparation is required, such ambient desorption/ionization techniques have been shown to provide direct, fast and selective fingerprinting characterization at the molecular level based on the pools of the most typical components. They have also been found to be applicable on intact, undisturbed samples or on simple solvent extracts. Fundamentals of EASI-MS and its sister techniques, including mechanisms, devices, parameters and strategies, as well as the many applications reported for food analysis, are summarized and discussed. PMID- 26820191 TI - [Recommendations to improve the scientific communication process in the Revista Medica del IMSS]. AB - In order to improve the position of the Revista Medica del Instituto Mexicano del Seguro Social among the different journals, in this editorial we enumerate a series of recommendations to ameliorate the practices of the different actors who participate in the scientific communication process of this journal. PMID- 26820192 TI - [Trend of antimicrobial susceptibility in a neonatal and pediatric intensive care unit]. AB - BACKGROUND: Nosocomial infections in intensive care units are a health problem worldwide due to their incidence, prevalence and clinical impact. The objective of this article was to describe the trend of antimicrobial susceptibility during a 10-years period in both a pediatric and a neonatal intensive care unit. METHODS: This is a follow-up cohort study. In 10 years of follow-up, the antimicrobial used was considered the independent variable, and the antimicrobial susceptibility as the dependent variable. By using chi squared with Fisher exact test, the initial and final susceptibilities were compared, and also the most prevalent diagnoses and the antimicrobials. A two-tailed p value < 0.05 was considered statistically significant. SPSS 8 and Epi-Info 0.6 were used for statistical analysis. RESULTS: Antimicrobial susceptibility decreased from 66 to 45 % in 10 years, representing a global loss of 13 % (p = 0.002). The most affected antimicrobials were first-generation cephalosporin (p = 0.02), ciprofloxacin (p = 0.05), erythromycin (p = 0.001), imipenem (p = 0.001), and trimethoprim/sulfamethoxazole (p = 0.05). CONCLUSION: There is an alarming loss of effectiveness in antimicrobial agents. PMID- 26820193 TI - [Lactate levels with regards to the pulse pressure in patients with shock]. AB - BACKGROUND: Lactate is one of the most useful biomarkers to screen patients with shock; therefore, the aim of this study was to establish the levels of lactate regarding the pulse pressure in that sort of patients. METHODS: Observational, retrospective, cross-sectional and descriptive study of patients over 18 years diagnosed with shock from an emergency room of a tertiary care hospital. Lactate levels and pulse pressure were used as biomarkers. We used descriptive statistics, Student's t test and Pearson correlation coefficient. RESULTS: We obtained 46 patients. The average age was 39.52 (SD 15.22), media initial lactate level was 5.88 mmol/L (SD 3.89) and media final lactate level 3.31 mmol/L (SD = 3.12); initial pulse pressure was 19.78 mmHg (SD 7.45) and final pulse pressure 31.52 mmHg (SD 31.52). The relation of secondary diagnosis did show predominance in chest trauma with 13 patients. There was a statistical significance in initial lactate and final lactate of r = 0.83 (p = 0.00), and initial pulse pressure and final pulse pressure: r = 0.57 (p = 0.001). There was not a significant correlation between final lactate and final pulse pressure (r: -0.184, p = 0.222). CONCLUSION: Even when several studies emphasize the clinical significance of biomarkers in the diagnosis and management of patients with hypovolemic shock, it is necessary to do more studies in order to find the efficacy of the non invasive screening in this type of pathology. PMID- 26820194 TI - [Microorganisms responsible of nosocomial infections in the Mexican Social Security Institute]. AB - BACKGROUND: The prevention and control of the nosocomial infections involve the knowledge of the most frequent type of microorganism isolated. In Mexico there are not national statistics to identify the main microorganisms that cause a nosocomial infection. METHODS: It was conducted an analysis of all the culture results of the nosocomial infections reported by the Sistema de Vigilancia Epidemiologica Hospitalaria (Epidemiological Surveillance System) of the Instituto Mexicano del Seguro Social during the year 2013. The most frequent and relevant microorganisms were reported. RESULTS: 48 377 results from cultures of nosocomial infections were studied. Of these 13 207 (27.3 %) were from 25 high specialty medical units and 35 170 (72.6 %) from 197 second level medical units. The most frequently isolated microorganism was Escherichia coli with 8192 results (16.9 %), followed by the group of Coagulase-negative Staphylococci with 6771 cultures (14 %) and Pseudomonas aeruginosa with 5275 results (19.9 %). Slight differences between levels of care and specialized hospitals were observed. CONCLUSION: This study identifies the Escherichia coli, the group of Coagulase negative Staphylococci and the Pseudomonas aeruginosa as the main microorganisms to prevent. PMID- 26820195 TI - [Analysis of the cumulative solar ultraviolet radiation in Mexico]. AB - BACKGROUND: The incidence of skin cancer has increased in Mexico in recent years. Ultraviolet radiation is the main risk factor associated. Due to the need to develop strategies to prevent skin cancer, the aim of the study was to estimate the UV intensity in several representative regions of Mexico, the average annual UV dose of these populations, and the potential benefit of applying sunscreen at different ages. METHODS: The intensity of UV radiation was quantified by remote and terrestrial radiometry. The dose of UV exposure was measured in minimal erythema doses using validated models for face and arms. The benefit of using a sunscreen was calculated with the use of a sunscreen with SPF 15 from birth to age 70. RESULTS: The UV radiation is lower in December and greater in the period from May to July. The region with a lower annual dose is Tijuana; and the higher annual dose is in the Mexico City area. The annual difference between these regions was 58 %. Through life, a low SPF sunscreen can reduce up to 66 % of the received UV dose. CONCLUSIONS: The geographical location is a risk factor for accumulation of UV radiation in Mexico. Since childhood, people receive high amounts of it; however, most of this dose can be reduced using any commercially available sunscreen, if applied strategically. PMID- 26820196 TI - [Antimicrobial resistance trends in pathogens isolated from nosocomial infections]. AB - BACKGROUND: The treatment of nosocomial infections is hindered by the increasing antimicrobial resistance pattern of germs that cause them. The objective was to assess trends in resistance of bacteria isolated from nosocomial infections. METHODS: Retrospective study from 2009 to 2012 on a third level hospital in Chiapas. RESULTS: 1300 germs were obtained, 62.3 % Gram negative bacteria, 22.8 % Gram positive and 14.9 % yeasts; imipenem resistance of P. aeruginosa went from 47.1 to 60.5 %, E. coli showed an increased resistance to aztreonam, cefepime and ceftazidime, A. baumannii increased resistance to amikacin, cefepime, ceftazidime and ciprofloxacin. Klebsiella pneumoniae decreased its resistance to amikacin and piperacillin/tazobactam; vancomycin resistance ranges from 3.6 to 25.5 %. CONCLUSION: Gram negative organisms predominated, showing increasing trends in antimicrobial resistance. There was a proportional increase in the incidence of infection from E. coli, C. tropicalis and S. haemolyticus. It is essential to have programs and plans for the rational and evidence-based use of antimicrobials, as well as dissemination and adherence to clinical practice guidelines and the implementation of innovative programs for the prevention and control of nosocomial infections, isolation techniques and general care. PMID- 26820197 TI - [Protein supplement consumption and its possible association with kidney damage in Mexican elite athletes]. AB - BACKGROUND: Protein supplements are one of the most used ergogenic supplements by elite athletes. Nonetheless, it has been postulated that the use of these type of supplements may cause chronic renal failure. The objective of this study is to analyze the effects of the consumption of protein supplements in the renal function of elite athletes of the Mexican Olympic Training Center. METHODS: 74 athletes provided urine samples in order to quantify urinary proteins. Some of them were excluded since they had conditions that could cause proteinuria or alter the quality of the samples. Those that were not excluded were divided into two groups: the experimental group, which included those individuals that had the antecedent of consuming protein supplements, and the control group, that encompassed those individuals that did not had the antecedent of consuming protein supplements. RESULTS: Of the 74 analyzed athletes, 44 were excluded, 11 individuals were included in the experimental group, and 19 in the control group. Microproteinuria was encountered in only one urine sample (control group), and it was determined that there was no significant differences between both groups. CONCLUSION: From the gathered results it can be concluded that protein supplements do not affect renal function. Nonetheless, in the future protein supplements should be evaluated in groups with pathologies or conditions that may compromise renal function. PMID- 26820198 TI - [Methicillin resistance and vancomycin susceptibility pattern among blood isolates of Staphylococcus aureus]. AB - BACKGROUND: Staphylococcus aureus is capable of acquiring resistance against all antimicrobial agents. Vancomycin has been the cornerstone therapy for serious methicillin-resistant S. aureus infections. However, vancomycin treatment failures have been reported. METHODS: From March to August 2010, S. aureus blood isolates were included to determine methicillin-resistance and the vancomycin susceptibility by using a standard microdilution method. To detect methicillin resistance, a Mueller-Hinton agar plate added with oxacillin 4 ug/mL and 2 % NaCl, and an agglutination test were used. Growth of S. aureus on the agar plate and/or reactive agglutination defined a methicillin-resistant organism. Vancomycin susceptibility was assessed by determining the minimal inhibitory concentration (MIC) in Muelller-Hinton agar plates prepared with dilutions ranging from 16 to 0.5 ug/mL. RESULTS: A total of 25 blood-isolates of S. aureus were included. A 60 % was methicillin-resistant. All isolates were vancomycin susceptible (MIC <= 2 ug/mL) showing the next MICs distribution: 48 % <= 0.5 ug/mL; 44 % 1 ug/mL, and 8 % 2 ug/mL. CONCLUSION: The high proportion of methicillin-resistance among S. aureus and the presence of vancomycin susceptible phenotypes (MIC of 2 ug/mL) not only claim for an enforcement of standard precautions and antimicrobial control, but also for a regular surveillance of vancomycin susceptibility pattern using a reference method. PMID- 26820199 TI - [HIV screening through rapid testing to pregnant women in the Family Medicine Unit 171]. AB - BACKGROUND: Coverage for HIV in our country through the rapid test has increased, from 8.2 % in 2006 to 59.8 % in 2012; however, it is still insufficient. The objective is to determine the prevalence of HIV screening through rapid testing to pregnant women in the Unidad de Medicina Familiar (UMF) 171. METHODS: It was carried out a descriptive cross-sectional study with non-probability sampling that included pregnant women of any age who came to birth control in the UMF 171 of the Instituto Mexicano del Seguro Social. Review of medical records was applied as a tool to gather information on the rapid test. A sample of 85 patients was calculated and descriptive statistical analysis was performed. RESULTS: 85 patient records were reviewed in control pregnancy. Rapid testing for detection of antibodies to HIV was performed in 79 patients (93 %). In nine (10 %) of the patients who underwent the test, the result was not reported in their file. In six patients (7 %) of the total sample the rapid test was not requested or performed. The result of all rapid tests reported was HIV negative. CONCLUSION: There is an increase in the coverage of rapid HIV testing in pregnant women; however, not reporting and not requesting the test are still common problems in the early detection of HIV infection in pregnant women. PMID- 26820200 TI - [Depression and risk factors associated in women with children in sessions with a child psychiatrist]. AB - BACKGROUND: Maternal depression entails cognitive, behavioral, affective and relational disorders with a great impact on the life quality of individuals, society and family. Our objective was to determine the prevalence and factors associated in women with children in paedopsychiatry treatment in a children's hospital. METHODS: Descriptive, prospective and prevalence study with a sample of 194 women. We used Beck scale. We calculated the prevalence rate. We analyzed the association of risk factors with the maternal depression by using chi square and a relative risk with a 95 % confidence interval (p = 0.5). RESULTS: There was a maternal prevalence depression of 66 %: 45 % had a mild depression (58), 35 % moderate (45) and 20 % severe (25). According to the chi square analysis, married female variable was statistically significant (8.7408, p = 0.0031, Odds Ratio [OR] 2.48). Having five children had an OR of 2.09, and the diagnosis of delay in the development an OR of 1.75. CONCLUSION: There was a higher prevalence than expected with a percentage difference of 6 points. Mild depression was more common; women from 31 to 40 years of age, married, and with five children were the most affected groups. PMID- 26820201 TI - [Indications for the use of continuous subcutaneous insulin infusion in pediatric patients with type 1 diabetes mellitus]. AB - BACKGROUND: Diabetes is a serious health problem for pediatrics. In pediatric patients control depends on correct insulin administration. The most usual is subcutaneous administration according to the glycemic control. The aim was to analyze the indications for continuous subcutaneous insulin infusion (CSII) in type 1 diabetes mellitus (T1DM) children and adolescents. METHODS: It was carried out a descriptive study in patients from 1 to 16 years with T1DM who underwent CSII therapy. The main cause to use this therapy was analyzed, and also if that cause was different regarding age, sex and disease progression. RESULTS: 61 patients underwent CSII therapy. The median age at the beginning of treatment was 9 years old; 43 patients (71.6 %) had more than one year of diagnosis. The main reasons to use CSII were: 42.6 % had to improve their quality of life, 34.4 % had to reduce the high glycemic variability, 13.1 % had to control severe recurrent hypoglycemia, and 9.8 % had to control their HbA1c. For children under 6 years of age (n = 14) the more frequent indication were recurrent hypoglycemia and to improve their quality of life; children from 6 to 12 years of age (n = 27) had to improve their quality of life, and in children over 12 years CSII was indicated for high glycemic variability and severe recurrent hypoglycemia. There was no different indication related between sexes. CONCLUSION: Improve their quality of life and reach a better glycemic control were the main reasons to start CSII in our patients. PMID- 26820202 TI - [Prevalence of urinary tract symptoms in women with diabetes mellitus]. AB - BACKGROUND: The objective was to evaluate the prevalence of urinary tract symptoms and the impact in the quality of life in women with diabetes, the association with DM and neuropathy evolution time and glycemic control. METHODS: A cohort of women from the DiabetIMSS program was evaluated from January 2011 to 2013. The personal history, time of DM diagnosis, neuropathy, urinary symptoms, glycemic control and quality of life impact were noted. RESULTS: A total of 169 women were evaluated. The median age was 58 years (29-85) and DM main evolution time was 9 years (0.5-31). Urinary tract symptoms were present in 128 (75.7 %) patients. Stress and urge incontinence were predominantly present (45.3 and 40.6 % respectively), followed by obstructive and irritative symptoms (25 and 10.1 % respectively). The impact in the quality of life was mild-moderate in 91.1 % of the patients. At least one criteria for neuropathy was noted in 154 (91.1 %) patients. Neuropathy evolution time was longer in the symptomatic group (12 vs 4.8 months). Symptoms were mainly present in patients with more than one year of neuropathy; p < 0.05. CONCLUSION: There is a high prevalence of urinary tract symptoms in diabetic women. The only associated risk factor was neuropathy. No significative association was found between the rest of the factors. PMID- 26820203 TI - [Comment on the article "Reflections on the concept of communication... "]. PMID- 26820204 TI - [Answer to comment on the article "Reflections on the concept of communication... "]. PMID- 26820205 TI - [Answer from the editors to comment on the article "Reflection on the concept of communication..."]. PMID- 26820206 TI - [Concerning the article "Four stages in the history of the Centro Medico Nacional Siglo XXI"]. PMID- 26820207 TI - [Comment on the article "Prevalence and implicated risk factors associated with the exteriorization of cardiac pacemakers... "]. PMID- 26820208 TI - [Answer to comment on the article "Prevalence and implicated risk factors associated with the exteriorization of cardiac pacemakers..."]. PMID- 26820210 TI - [Scientific contributions of Jules Hirsch regarding the physiopathogenesis of obesity]. AB - Jules Hirsch was born in New York City and died at age 88 after a long illness. He was considered notorious leader in the study of human metabolism mainly in the area of lipids and obesity. His research at The Rockefeller University helps establish the mechanism of obesity and lipids metabolism. Hirsch joined Rockefeller's faculty in 1954 and remained there for the rest of his career. Hirsch's research helped to support the idea of dynamic interactions among diet, physical activity, general metabolism and obesity. At that time most scientific considered adipose tissue to be biologically inert such as a passive insulator in which the body reserved energy in the form of triglycerides. Hirsch had a natural characteristic of showing a nice smile and greeting for everyone he worked with at the university. Another important contribution was there relationship between diet and cardiovascular ailments as well as metabolism disturbance. PMID- 26820209 TI - [Methodology for the development and update of practice guidelines: current state]. AB - The current scenario of health services in Mexico reveals as a priority the implementation of strategies that allow us to better respond to the needs and expectations of individuals and society as a whole, through the provision of efficient and effective alternatives for the prevention, diagnosis and treatment of diseases. In this context, clinical practice guidelines constitute an element of management in the health care system, whose objective is to establish a national bechmark for encouraging clinical and management decision making, based on recommendations from the best available evidence, in order to contribute to the quality and effectiveness of health care. The purpose of this document is to show the methodology used for the development and updating of clinical practice guidelines that the Instituto Mexicano del Seguro Social has developed in line with the sectorial model in order to serve the user of these guidelines. PMID- 26820211 TI - [Pharmacists in transition. Academy and Pharmacy in Mexico from 1833 to 1865]. AB - From the second half of the 19th century, health disciplines went through an institutional and professional restructuring, which progressively altered the guild order that had characterized them to that point. In the case of Pharmacy, this process implied the generation of officially recognized spaces, as the chairs of Pharmacy and Medical Substance, founded during the Establecimiento de Ciencias Medicas (Establishment of Medical Sciences) (1833). In those spaces it was sought to institutionalize knowledge and modern practices related to Pharmacy. In this work we look over the first academic experience of the pharmaceutical community in that new space of instruction, based on the records belonging to the students enrolled in the Establecimiento de Ciencias Medicas from 1833 to 1865, year of the enrollment of the last generation. The information contained in those 163 records displays the way the pharmaceutical field was transformed, after the aforementioned restructuring. The reader will notice the diverse normativity, which regulated the joining of pharmacists to academic life (of which, until then, they were excluded). He will also realize how, among the first students enrolled in the Establecimiento de Ciencias Medicas, said normativity was broke in order to adapt it to the known ways of students and professors. Progressively, the guild instruction would be ousted by the institutional instruction (for example, the years of practice in the drugstores were rejected), so that the guild ways of teaching were changing to turn the pharmacist into an individual of institutional instruction. PMID- 26820212 TI - [Neuhauser syndrome: the facial dysmorphic phenotype]. AB - Neuhauser syndrome is an extremely rare genetic disease, most cases are sporadic by spontaneous mutation, but there are cases of autosomal recessive genetic transmission; the specific cause is unknown and has no diagnostic test. The disease is clinically characterized by primary megalocornea, congenital hypotonia, mental retardation of varying degree and delayed psychomotor development. The diagnosis in childhood is usually performed by oculo neurological criteria. The patients have a peculiar face by specific craniofacial anomalies: round face, wide prominent forehead, hypertelorism, broad nasal bridge, bulbous nose, wide philtrum nasolabial wide, thin elongated mouth, big and protuded ear "cup", jaw undersized (micrognathia) and abnormal posterior positioning of the mandible (retrognathia).The use of facial dysmorphism helps to delineate the phenotype and achieve the punctuation required for the diagnosis, allowing early management and prevention of complications. PMID- 26820213 TI - [Current diagnosis and treatment of hyperprolactinemia]. AB - Hyperprolactinemia is a frequent neuroendocrinological condition that should be approached in an orderly and integral fashion, starting with a complete clinical history. Once physiological causes such as pregnancy, systemic disorders such as primary hypothyroidism and the use of drugs with dopamine antagonistic actions such as metochlopramide have been ruled out, the most common cause of hyperprolactinemia is a PRL-secreting pituitary adenoma or prolactinoma. Prolactinomas are usually classified as microprolactinomas (less than 1 cm) or macroprolactinomas (larger than 1 cm), which can either be confined or invasive. The hormonal consequence of hypeprolactinemia is hypogonadism; in women, this is manifested as amenorrhea/oligomenorreha, anovulation and galactorrhea, whereas in men the main complaints are a diminished libido and erectile dysfunction. Macroprolactinomas can also present with symptoms and signs resulting form mass effect of the tumor, such as headaches and visual field defects. Other structural causes of hyperprolactinemia include non-functioning pituitary adenomas and infiltrative disorders, which can interrupt the inhibitory, descending dopaminergic tone. The primary treatment of prolactinomas is pharmacological with dopamine agonists such as cabergoline. PMID- 26820214 TI - [Diagnostic strategies in the Tuberculosis Clinic of the Hospital General La Raza National Medical Center]. AB - In order to diagnose TB infection, tuberculin skin test and interferon gamma release assay are available. The tuberculin test has a sensitivity of 99 % and a specificity of 95 %. For the detection of interferon gamma in blood there are currently two tests available: TBGold QuantiFERON-In-Tube (with a sensitivity of 0.70 and a specificity of 0.90), and T-SPOT-TB (sensitivity 0.90 and specificity 0.93). To diagnose the disease, a microscopy of direct smears for acid-fast bacilli is used if the physician is facing an extensive cavitary lung disease due to M. tuberculosis (this test has a high sensitivity: 80-90 %). The most common staining techniques used are Ziehl-Neelsen and Kinyoun, and the fluorescent technique, auramine-rhodamine. The culture is the gold standard and it has a sensitivity of 80 % and a specificity over 90 %, but the results take weeks. The nucleic acid amplification test has an overall sensitivity and specificity of 0.85 and 0.97, respectively. In the presence of a pleural effusion is necessary to perform a pleural biopsy for culture with a sensitivity of 85 % if it is percutaneous and 98 % if it was taken by thoracoscopy. The adenosine deaminase can be determined in pleural fluid with a sensitivity and specificity of 95 %. PMID- 26820215 TI - [Effectiveness of the outpatient treatment of the community-acquired pneumonia: systematic review and meta-analysis]. AB - BACKGROUND: Community-acquired pneumonia is an important cause of mortality and morbidity worldwide. Therefore, our aim was to assess the efficacy and safety of outpatient treatment of community-acquired pneumonia. METHODS: We systematically reviewed randomized clinical trials evaluating efficacy and safety of outpatient treatment (OPT) compared with inpatient treatment (IPT) of community-acquired pneumonia in patients without added co-morbidity. Relative Risk (RR) and 95 % confidence interval (95 % CI) were calculated. RESULTS: From 4088 reviewed articles, two articles were included for meta-analysis, including 2324 patients. One study was conducted in adults, and the other was carried out in pediatric patients. Treatment setting was not significantly associated with treatment failure (RR 0.84 [95% CI 0.68, 1.02]). Death occurred in 6 of 2324 with no difference between the two groups (RR 0.56 [95 % CI 0.12-2.61]). Finally, no differences were seen in hospital readmission between groups (RR 0.82 [95 % CI 0.52-1.30]). CONCLUSION: Evidence shows that treatment setting of community acquired pneumonia is not statistically associated with treatment failure or mortality. PMID- 26820216 TI - Vasopressin and sympathetic system mediate the cardiovascular effects of the angiotensin II in the bed nucleus of the stria terminalis in rat. AB - The bed nucleus of the stria terminalis (BST) is involved in cardiovascular regulation. The angiotensin II (Ang II) receptor (AT1), and angiotensinogen were found in the BST. In our previous study we found that microinjection of Ang II into the BST produced a pressor response. This study was performed to find the mechanisms mediating this response in anesthetized rats. Ang II was microinjected into the BST and the cardiovascular responses were re-tested after systemic injection of a blocker of autonomic or vasopressin V1 receptor. The ganglionic nicotinic receptor blocker, hexamethonium dichloride, attenuated the pressor response to Ang II, indicating that the cardiovascular sympathetic system is involved in the pressor effect of Ang II. A selective vasopressin V1 receptor antagonist greatly attenuated the pressor effect of Ang II, indicating that the Ang II increases the arterial pressure via stimulation of vasopressin release as well. In conclusion, in the BST, Ang II as a neurotransmitter increases blood pressure by exciting cardiovascular sympathetic system and directly or indirectly causing vasopressin to release into bloodstream by VPN. This is an interesting new finding that not only circulating Ang II but also brain Ang II makes vasopressin release. PMID- 26820217 TI - Body representation in the brain. PMID- 26820218 TI - Cell survival of glioblastoma grown in medium containing hydrogen peroxide and/or nitrite, or in plasma-activated medium. AB - Non-equilibrium atmospheric pressure plasmas generate a high electron density (on the order of 10(16) electrons per cm(-3)) using Ar gas. Culture medium in air at room temperature was plasma-irradiated for several hundred seconds. Tens of micromolar hydrogen peroxide (H2O2) and millimolar levels of nitrous ion (NO2(-)) were detected in the plasma-irradiated culture medium (plasma activated medium; PAM) and selectively induced the apoptotic death of glioblastoma tumor cells, but did not kill normal mammary epithelial cells. A similar antitumor effect was induced by spiking the medium with comparable concentrations of H2O2 and NO2(-). The PAM remained still a somewhat difference that it should also be assessed for understanding other latent mechanisms. PMID- 26820219 TI - Tanshinone IIA affects the HDL subfractions distribution not serum lipid levels: Involving in intake and efflux of cholesterol. AB - AIM OF STUDY: Tanshinone IIA is an active component of the traditional Chinese medicine. This study aimed at investigating the mechanism of tanshinone IIA on anti-atherosclerosis, which may be because of that Tanshinone IIA can affect the HDL subfractions distribution and then regulate reverse cholesterol transport. MATERIALS AND METHODS: A model of hyperlipidaemia in rats was used. Tanshinone IIA was given daily after hyperlipidaemia. In vivo, lipid deposition and morphological changes in liver were analyzed; HDL subfractions and lipid level in serum as well as in liver were measured; the expression of genes related to cholesterol intake in liver and peritoneal macrophage cholesterol efflux were evaluated. In vitro, HepG2 cells and THP-1 cells were pretreated with tanshinone IIA and subsequently with ox-LDL to evaluate the total cholesterol and the expression of related genes. RESULTS: Tanshinone IIA reduced the lipid deposition in liver. Moreover, it did not affect the serum lipid levels but reduced the levels of HDL middle subfractions and increased the levels of HDL large subfractions. Furthermore, tanshinone IIA could regulate the expressions of CYP7A1, LDL-R, SREBP2 and LCAT in the liver as well as the ABCA1 and CD36 in macrophage cells which is involving in the cholesterol intake and efflux respectively. It could reduce lipid accumulation caused by ox-LDL induction, and that also regulate the expressions of LDL-R, HMGCR and SREBP2 in HepG2 and ABCA1, CD36 in THP-1 cells. CONCLUSION: A novel finding that tanshinone IIA was not reduce the serum lipid level but affects the HDL subfractions distribution and thereby regulating the intake and efflux of cholesterol. PMID- 26820220 TI - Sustained lung inflation in late preterm infants: a randomized controlled trial. AB - OBJECTIVE: To assess the need for respiratory support in late preterm infants treated with sustained lung inflation (SLI) at birth. STUDY DESIGN: In this controlled trial, we randomly assigned infants born at 34(+0) to 36(+6) weeks of gestation to receive SLI (25 cmH2O for 15 s) at birth, followed by continuous positive airway pressure (CPAP) or assistance according to the recommendations of the American Academy of Pediatrics. The primary outcome was the need for any type of respiratory support. The secondary outcomes included neonatal intensive care unit (NICU) admission for respiratory distress and length of stay. The risk ratios (RRs) and 95% confidence intervals (CIs) of the outcomes were calculated for the SLI group in reference to the control group. RESULTS: A total of 185 infants were enrolled: 93 in the SLI group and 92 in the control group. No difference was found in the need for any type of respiratory support between the infants treated with SLI and the control group (10.6 vs 8.7%, RR 1.24, 95% CI 0.51 to 2.99). The NICU admission for respiratory distress and the length of stay did not differ between the groups. CONCLUSION: Providing SLI at birth in late preterm infants does not affect their need for respiratory support. PMID- 26820222 TI - Shotgun proteomics to unravel marine mussel (Mytilus edulis) response to long term exposure to low salinity and propranolol in a Baltic Sea microcosm. AB - Pharmaceuticals, among them the beta-adrenoceptor blocker propranolol, are an important group of environmental contaminants reported in European waters. Laboratory exposure to pharmaceuticals on marine species has been performed without considering the input of the ecosystem flow. To unravel the ecosystem response to long-term exposure to propranolol we have performed long-term exposure to propranolol and low salinity in microcosms. We applied shotgun proteomic analysis to gills of Mytilus edulis from those Baltic Sea microcosms and identified 2071 proteins with a proteogenomic strategy. The proteome profiling patterns from the 587 highly reproductive proteins among groups define salinity as a key factor in the mussel's response to propranolol. Exposure at low salinity drives molecular mechanisms of adaptation based on a decrease in the abundance of several cytoskeletal proteins, signalling and intracellular membrane trafficking pathway combined with a response towards the maintenance of transcription and translation. The exposure to propranolol combined with low salinity modulates the expression of structural proteins including cilia functions and decreases the expression of membrane protein transporters. This study reinforces the environment concerns of the impact of low salinity in combination with anthropogenic pollutants and anticipates critical physiological conditions for the survival of the blue mussel in the northern areas. BIOLOGICAL SIGNIFICANCE: Applying shotgun proteomic analysis to M. edulis gills samples from a long-term microcosm exposure to propranolol and following a proteogenomic identification strategy, we have identified 2071 proteins. The proteomic analysis unrevealed which molecular mechanisms drive the adaptation to low salinity stress and how salinity modulates the effects of exposure to propranolol. These results reinforce the idea of the impact of low salinity in combination with anthropogenic pollutants and anticipate critical physiological condition. PMID- 26820221 TI - Comparative effectiveness of two outreach strategies for cervical cancer screening. AB - OBJECTIVE: Test-specific reminder letters can improve cancer screening adherence. Little is known about the effectiveness of a reminder system that targets the whole person by including multiple screening recommendations per letter. METHODS: We compared the effectiveness of a Pap-specific reminder letter sent 27months after a woman's last Pap, to a reminder letter that included up to seven preventive service recommendations sent before a woman's birthday ("birthday letter") on Pap smear adherence from a natural experiment occurring in routine clinical care. Participants included 82,016 women from Washington State who received 72,615 Pap-specific letters between 2003 and 2007 and 100,218 birthday letters between 2009 and 2012. We defined adherence as having a Pap test within a six month window around the Pap test due date. Using logistic regression, we calculated adjusted odds ratios (OR) for adherence with 95% confidence intervals (CI) following the birthday letter with 1-2 recommendations, 3-5 recommendations, and 6-7 recommendations compared to the Pap-specific letter. All analyses were stratified by whether a woman was up-to-date or overdue for screening at the time she received a letter. RESULTS: Adjusted ORs showed reduced adherence following the birthday letter compared with the Pap-specific letter for up-to-date women whether the letter had 1-2 recommendations (OR=0.37, 95%CI=0.36-0.39), 3-5 recommendations (OR=0.44, 95%CI=0.42-0.45), or 6-7 recommendations (OR=0.36, 95%CI=0.32-0.40). We noted no difference in Pap-test adherence between letter types for overdue women. CONCLUSIONS: In conclusion, for women regularly adherent to screening, an annual birthday letter containing reminders for multiple preventive services was less effective at promoting cervical cancer screening compared with a Pap-specific letter. PMID- 26820223 TI - Effectiveness of antiepileptic therapy in patients with PCDH19 mutations. AB - PURPOSE: PCDH19 mutations cause epilepsy and mental retardation limited to females (EFMR) or Dravet-like syndromes. Especially in the first years of life, epilepsy is known to be highly pharmacoresistant. The aim of our study was to evaluate the effectiveness of antiepileptic therapy in patients with PCDH19 mutations. METHODS: We report a retrospective multicenter study of antiepileptic therapy in 58 female patients with PCDH19 mutations and epilepsy aged 2-27 years (mean age 10.6 years). RESULTS: The most effective drugs after 3 months were clobazam and bromide, with a responder rate of 68% and 67%, respectively, where response was defined as seizure reduction of at least 50%. Defining long-term response as the proportion of responders after 12 months of treatment with a given drug in relation to the number of patients treated for at least 3 months, the most effective drugs after 12 months were again bromide and clobazam, with a long-term response of 50% and 43%, respectively. Seventy-four percent of the patients became seizure-free for at least 3 months, 47% for at least one year. SIGNIFICANCE: The most effective drugs in patients with PCDH19 mutations were bromide and clobazam. Although epilepsy in PCDH19 mutations is often pharmacoresistant, three quarters of the patients became seizure-free for at least for 3 months and half of them for at least one year. However, assessing the effectiveness of the drugs is difficult because a possible age-dependent spontaneous seizure remission must be considered. PMID- 26820224 TI - In vivo evidence of a functional association between immune cells in blood and brain in healthy human subjects. AB - Microglia, the resident macrophages in the central nervous system, are thought to be maintained by a local self-renewal mechanism. Although preclinical and in vitro studies have suggested that the brain may contain immune cells also from peripheral origin, the functional association between immune cells in the periphery and brain at physiological conditions is poorly understood. We examined 32 healthy individuals using positron emission tomography (PET) and [(11)C]PBR28, a radioligand for the 18-kDa translocator protein (TSPO) which is expressed both in brain microglia and blood immune cells. In 26 individuals, two measurements were performed with varying time intervals. In a subgroup of 19 individuals, of which 12 had repeat examinations, leukocyte numbers in blood was measured on each day of PET measurements. All individuals were genotyped for TSPO polymorphism and categorized as high, mixed, and low affinity binders. We assessed TSPO binding expressed as total distribution volume of [(11)C]PBR28 in brain and in blood cells. TSPO binding in brain was strongly and positively correlated to binding in blood cells both at baseline and when analyzing change between two PET examinations. Furthermore, there was a significant correlation between change of leukocyte numbers and change in TSPO binding in brain, and a trend-level correlation to change in TSPO binding in blood cells. These in vivo findings indicate an association between immunological cells in blood and brain via intact BBB, suggesting a functional interaction between these two compartments, such as interchange of peripherally derived cells or a common regulatory mechanism. Measurement of radioligand binding in blood cells may be a way to control for peripheral immune function in PET studies using TSPO as a marker of brain immune activation. PMID- 26820225 TI - The role of microbiota in cancer therapy. AB - The relationship between the host and the commensal microbiota regulates physiological functions including inflammation and immunity and it has been scrutinized in the context of cancer. While viruses and bacterial species have been implicated in oncogenesis, commensal microbes also have a beneficial role in the fight against cancer. Therapy efficacy, including adoptive T cell transfer, alkylating agents and immune checkpoint blockers, relies on immunity that receives its education from the gut microbiota. In cancer therapy with immunostimulating oligonucleotides and platinum salts, the microbiota also modulates the response by priming for the release of pro-inflammatory factors and reactive oxygen species, respectively. This new information offers promising clinical possibilities of modulating cancer therapy and its toxic side effects by targeting the microbiota. PMID- 26820227 TI - MicroRNA-187, a downstream effector of TGFbeta pathway, suppresses Smad-mediated epithelial-mesenchymal transition in colorectal cancer. AB - Constitutive overactivation of TGFbeta signaling is a common event in human cancer progression and acts as a major inducer of epithelial-mesenchymal transition (EMT). In pre-metastatic colorectal cancer (CRC) cells, however, this cascade is tightly controlled and the underlying mechanism in TGFbeta stimulated hyperactivation of downstream Smad pathway remains elusive. In this study, expression of miR-187 was downregulated in colorectal cancer (CRC) compared with adjacent normal tissues. miR-187 could suppress the formation of aggressive phenotype in CRC and inactivate Smad pathway, thus preventing EMT. TGFbeta stimulation significantly suppressed the expression of miR-187, and overexpressed miR-187 counteracted the influence of TGFbeta on cell phenotype and downstream pathway. Furthermore, we found that miR-187 directly suppressed the expression of SOX4, NT5E and PTK6, which were identified as essential upstream effectors of Smad pathway. Together with the fact that high SOX4 or NT5E levels were associated with poor prognosis, we also demonstrated that downregulation of miR 187 was closely related to tumor metastasis and poor prognosis in CRC. These findings revealed a plausible mechanism for sustained TGFbeta activation in cancer progression and might have suggested a novel miR-187-based clinical intervention target for patients with advanced CRC. PMID- 26820226 TI - Growth and toxin production of Azadinium poporum strains in batch cultures under different nutrient conditions. AB - Azaspiracid-2 (AZA2) is the dominant toxin produced by Azadinium poporum strains AZDY06 and AZFC22 isolated from the South China Sea. Biomass and AZA2-production were examined within batch cultures with variation in experimental concentrations of nitrate (0, 88, 882, and 2647uM) or phosphate (0, 3.6, 36, and 109uM), different nitrogen sources (nitrate and urea) and media (f/2-Si, L1-Si, and K-Si) in the present study. Growth of both strains positively responded to nitrate or phosphate nutrients, but the growth status was significantly repressed by the highest additional level of phosphate (109uM). Both AZDY06 and AZFC22 grew well with higher specific growth rates, but with shorter growth periods, within f/2-Si medium spiked with urea than that within media spiked with nitrate. L1-Si medium with relatively high concentrations of trace metals was relatively favorable to both strains of A. poporum tested here. No obvious change within the toxin profile occurred in all cultures of both strains under the various nutrient conditions, although trace amounts of some suspicious derivatives of AZA2 occurred in some cultures. AZA2 cell quotas within both strains significantly (p<0.05) increased at the stationary phase under lower additional phosphate (0 and 3.6uM). Significant differences were not found within AZA2 cell quotas in cultures with additional nitrate ranging from 0 to 2647uM. The highest AZA2 cell quota and maximum AZA2 quantity per culture volume occurred in batch culture at the stationary phase under phosphate concentrations at 3.6uM. Neither A. poporum strain exhibited significant changes in AZA2 cell quotas within f/2-Si media spiked with urea or nitrate as nitrogen sources. The AZA2 cell quota of strain AZDY06 also did not change remarkably within f/2-Si, L1-Si, and K-Si media, however the AZA2 cell quota of strain AZFC22 within L1-Si medium was significantly (p<0.05) higher than that within f/2-Si medium. PMID- 26820228 TI - Long-term prognostic significance of admission plateletcrit values in patients with non-ST elevation myocardial infarction. AB - The plateletcrit has been investigated as a new predictor of cardiovascular risk. The objective of our study was to investigate the role of admission plateletcrit in predicting long-term cardiovascular mortality in patients presenting with non ST-segment elevation myocardial infarction (NSTEMI). We enrolled 296 patients with NSTEMI (mean age 59.2 +/- 11.8 years; 228 men, 68 women) in this study. The study population was divided into tertiles on the basis of admission plateletcrit values. A high plateletcrit (n = 98) was defined as a value in the upper third tertile (plateletcrit >0.23), and a low plateletcrit (n = 198) was defined as any value in the lower two tertiles (plateletcrit <=0.23). The median follow-up time was 38 months. In multivariate analyses, a significant association was noted between high plateletcrit values and the adjusted risk of long-term mortality (odds ratio = 12.15, 95% confidence interval = 1.78-82.77; P < 0.001). In the Kaplan-Meier survival analysis, the long-term mortality rate was 20.4% in the high plateletcrit group versus 4.5% in the low plateletcrit group (P < 0.001). Long-term major advanced cardiac events (MACE), hospitalization for heart failure and reinfarction were significantly higher in patients with high plateletcrit. Admission plateletcrit is a strong and independent predictor of long-term cardiovascular mortality in patients with NSTEMI. PMID- 26820229 TI - Post-Formation Shrinkage and Stabilization of Microfluidic Bubbles in Lipid Solution. AB - Medical ultrasound imaging often employs ultrasound contrast agents (UCAs), injectable microbubbles stabilized by shells or membranes. In tissue, the compressible gas cores can strongly scatter acoustic signals, resonate, and emit harmonics. However, bubbles generated by conventional methods have nonuniform sizes, reducing the fraction that resonates with a given transducer. Microfluidic flow-focusing is an alternative production method which generates highly monodisperse bubbles with uniform constituents, enabling more-efficient contrast enhancement than current UCAs. Production size is tunable by adjusting gas pressure and solution flow rate, but solution effects on downstream stable size and lifetime have not been closely examined. This study therefore investigated several solution parameters, including the DSPC/DSPE-PEG2000 lipid ratio, concentration, viscosity, and preparation temperature to determine their effects on stabilization. It was found that bubble lifetime roughly correlated with stable size, which in turn was strongly influenced by primary-lipid-to-emulsifier ratio, analogous to its effects on conventional bubble yield and Langmuir-trough compressibility in existing studies. Raising DSPE-PEG2000 fraction in solution reduced bubble surface area in proportion to its reduction of lipid packing density at low compression in literature. In addition, the surface area was found to increase proportionately with lipid concentration above 2.1 mM. However, viscosities above or below 2.3-3.3 mPa.s seemed to reduce bubble size. Finally, lipid preparation at room temperature led to smaller bubbles compared to preparation near or above the primary lipid's phase transition point. Understanding these effects will further improve on postformation control over microfluidic bubble production, and facilitate size-tuning for optimal contrast enhancement. PMID- 26820230 TI - Hygroscopic Behavior of Multicomponent Aerosols Involving NaCl and Dicarboxylic Acids. AB - Atmospheric aerosols are usually complex mixtures of inorganic and organic compounds. The hygroscopicity of mixed particles is closely related to their chemical composition and interactions between components, which is still poorly understood. In this study, the hygroscopic properties of submicron particles composed of NaCl and dicarboxylic acids including oxalic acid (OA), malonic acid (MA), and succinic acid (SA) with various mass ratios are investigated with a hygroscopicity tandem differential mobility analyzer (HTDMA) system. Both the Zdanovskii-Stokes-Robinson (ZSR) method and extended aerosol inorganics model (E AIM) are applied to predict the water uptake behaviors of sodium chloride/dicarboxylic acid mixtures. For NaCl/OA mixed particles, the measured growth factors were significantly lower than predictions from the model methods, indicating a change in particle composition caused by chloride depletion. The hygroscopic growth of NaCl/MA particles was well described by E-AIM, and that of NaCl/SA particles was dependent upon mixing ratio. Compared with model predictions, it was determined that water uptake of the NaCl/OA mixture could be enhanced and could be closer to the predictions by addition of levoglucosan or malonic acid, which retained water even at low relative humidity (RH), leading to inhibition of HCl evaporation during dehydration. These results demonstrate that the coexisting hygroscopic species have a strong influence on the phase state of particles, thus affecting chemical interactions between inorganic and organic compounds as well as the overall hygroscopicity of mixed particles. PMID- 26820231 TI - Correction to "A New Interleukin-13 Amino-Coated Gadolinium Metallofullerene Nanoparticle for Targeted MRI Detection of Glioblastoma Tumor Cells". PMID- 26820232 TI - Splitting of Interlayer Shear Modes and Photon Energy Dependent Anisotropic Raman Response in N-Layer ReSe2 and ReS2. AB - We investigate the interlayer phonon modes in N-layer rhenium diselenide (ReSe2) and rhenium disulfide (ReS2) by means of ultralow-frequency micro-Raman spectroscopy. These transition metal dichalcogenides exhibit a stable distorted octahedral (1T') phase with significant in-plane anisotropy, leading to sizable splitting of the (in-plane) layer shear modes. The fan-diagrams associated with the measured frequencies of the interlayer shear modes and the (out-of-plane) interlayer breathing modes are perfectly described by a finite linear chain model and allow the determination of the interlayer force constants. Nearly identical values are found for ReSe2 and ReS2. The latter are appreciably smaller than but on the same order of magnitude as the interlayer force constants reported in graphite and in trigonal prismatic (2Hc) transition metal dichalcogenides (such as MoS2, MoSe2, MoTe2, WS2, WSe2), demonstrating the importance of van der Waals interactions in N-layer ReSe2 and ReS2. In-plane anisotropy results in a complex angular dependence of the intensity of all Raman modes, which can be empirically utilized to determine the crystal orientation. However, we also demonstrate that the angular dependence of the Raman response drastically depends on the incoming photon energy, shedding light on the importance of resonant exciton-phonon coupling in ReSe2 and ReS2. PMID- 26820233 TI - Effects of HSP27 downregulation on PDT resistance through PDT-induced autophagy in head and neck cancer cells. AB - We previously reported that photodynamic therapy (PDT) induces cell death in head and neck cancer through both autophagy and apoptosis. Regulation of cell death by autophagy and apoptosis is important to enhance the effects of PDT. Autophagy maintains a balance between cell death and PDT resistance. Downregulation of heat shock protein 27 (HSP27) induces PDT resistance in head and neck cancer cells. Furthermore, HSP70 regulates apoptosis during oxidative stress. However, the role of HSPs in PDT-induced cell death through autophagy and apoptosis is unclear. Therefore, in the present study, we investigated the effects of HSP27 and HSP70 on PDT-induced cell death of oral cancer cells through autophagy and apoptosis. Cancer cells were treated with hematoporphyrin at varying doses, followed by irradiation at 635 nm with an energy density of 5 mW/cm2. We determined the changes in HSP expression by determining the levels of PARP-1 and LC3II in PDT resistant cells. Furthermore, we assessed cell death signaling after downregulating HSPs by transfecting specific siRNAs. We observed that PDT decreased HSP27 expression but increased HSP70 expression in the head and neck cancer cells. Treatment of cells with LC3II and PARP-1 inhibitors resulted in upregulation of HSP70 and HSP27 expression, respectively. Downregulation of HSP27 and HSP70 induced cell death and PDT resistance through autophagy and apoptosis. Moreover, downregulation of HSP27 in PDT-resistant cells resulted in enhanced survival. These results indicate that the regulation of HSP27 and HSP70 plays a principal role in increasing the effects of PDT by inducing autophagic and apoptotic cell death. PMID- 26820235 TI - Post-Transition State Dynamics in Gas Phase Reactivity: Importance of Bifurcations and Rotational Activation. AB - Beyond the established use of thermodynamic vs kinetic control to explain chemical reaction selectivity, the concept of bifurcations on a potential energy surface (PES) is proving to be of pivotal importance with regard to selectivity. In this article, we studied by means of post-transition state (TS) direct dynamics simulations the effect that vibrational and rotational excitation at the TS may have on selectivity on a bifurcating PES. With this aim, we studied the post-TS unimolecular reactivity of the [Ca(formamide)](2+) ion, for which Coulomb explosion and neutral loss reactions compete. The PES exhibits different kinds of nonintrinsic reaction coordinate (IRC) dynamics, among them PES bifurcations, which direct the trajectories to multiple reaction paths after passing the TS. Direct dynamics simulations were used to distinguish between the bifurcation non IRC dynamics and non-IRC dynamics arising from atomistic motions directing the trajectories away from the IRC. Overall, we corroborated the idea that kinetic selectivity often does not reduce to a simple choice between paths with different barrier heights and instead dynamical behavior after passing the TS may be crucial. Importantly, rotational excitation may play a pivotal role on the reaction selectivity favoring nonthermodynamic products. PMID- 26820234 TI - Isotopic Ratio Outlier Analysis of the S. cerevisiae Metabolome Using Accurate Mass Gas Chromatography/Time-of-Flight Mass Spectrometry: A New Method for Discovery. AB - Isotopic ratio outlier analysis (IROA) is a (13)C metabolomics profiling method that eliminates sample to sample variance, discriminates against noise and artifacts, and improves identification of compounds, previously done with accurate mass liquid chromatography/mass spectrometry (LC/MS). This is the first report using IROA technology in combination with accurate mass gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS), here used to examine the S. cerevisiae metabolome. S. cerevisiae was grown in YNB media, containing randomized 95% (13)C, or 5%(13)C glucose as the single carbon source, in order that the isotopomer pattern of all metabolites would mirror the labeled glucose. When these IROA experiments are combined, the abundance of the heavy isotopologues in the 5%(13)C extracts, or light isotopologues in the 95%(13)C extracts, follows the binomial distribution, showing mirrored peak pairs for the molecular ion. The mass difference between the (12)C monoisotopic and the (13)C monoisotopic equals the number of carbons in the molecules. The IROA-GC/MS protocol developed, using both chemical and electron ionization, extends the information acquired from the isotopic peak patterns for formulas generation. The process that can be formulated as an algorithm, in which the number of carbons, as well as the number of methoximations and silylations are used as search constraints. In electron impact (EI/IROA) spectra, the artifactual peaks are identified and easily removed, which has the potential to generate "clean" EI libraries. The combination of chemical ionization (CI) IROA and EI/IROA affords a metabolite identification procedure that enables the identification of coeluting metabolites, and allowed us to characterize 126 metabolites in the current study. PMID- 26820236 TI - Association between XPG polymorphisms and stomach cancer susceptibility in a Chinese population. AB - Xeroderma pigmentosum group G (XPG) protein plays an important role in the DNA repair process by cutting the damaged DNA at the 3' terminus. Previous studies have indicated some polymorphisms in the XPG gene are associated with stomach cancer susceptibility. We performed this hospital-based case-control study to evaluate the association of four potentially functional XPG polymorphisms (rs2094258 C>T, rs751402 C>T, rs2296147 T>C and rs873601G>A) with stomach cancer susceptibility. The four single nucleotide polymorphisms (SNPs) were genotyped in 692 stomach cancer cases and 771 healthy controls. Logistic regression analysis was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association of interest. Of the studied SNPs, XPG rs873601G>A polymorphism was found to significantly associate with stomach cancer susceptibility (AA versus GG/AG: OR = 1.31, 95% CI = 1.03-1.66, P = 0.027). Combined analysis of all SNPs revealed that the individuals with two of risk genotypes had a significantly increased stomach cancer risk (OR = 1.52, 95% CI = 1.13-2.06). In the stratification analysis, the association between the rs873601AA genotype and stomach cancer risk was observed in older group (>59 year), as well as patients with non-cardia stomach cancer. Further combined analysis indicated men, smokers, or non-drinkers more than one risk genotypes had a significantly increased stomach cancer risk. Our results indicate that XPG rs873601G>A polymorphism may be associated with the risk of stomach cancer. Further prospective studies with different ethnicities and large sample sizes are needed to validate our findings. PMID- 26820237 TI - Prognostic Value of Fragmented QRS on Admission in Non-ST-Elevation Myocardial Infarction. PMID- 26820239 TI - Effects of triclosan on host response and microbial biomarkers during experimental gingivitis. AB - AIM: This exploratory randomized, controlled clinical trial sought to evaluate anti-inflammatory and -microbial effects of triclosan during experimental gingivitis as assessed by host response biomarkers and biofilm microbial pathogens. MATERIALS AND METHODS: Thirty participants were randomized to triclosan or control dentifrice groups who ceased homecare for 21 days in an experimental gingivitis (EG) protocol. Plaque and gingival indices and saliva, plaque, and gingival crevicular fluid (GCF) were assessed/collected at days 0, 14, 21 and 35. Levels and proportions of 40 bacterial species from plaque samples were determined using checkerboard DNA-DNA hybridization. Ten biomarkers associated with inflammation, matrix degradation, and host protection were measured from GCF and saliva and analysed using a multiplex array. Participants were stratified as "high" or "low" responders based on gingival index and GCF biomarkers and bacterial biofilm were combined to generate receiver operating characteristic curves and predict gingivitis susceptibility. RESULTS: No differences in mean PI and GI values were observed between groups and non significant trends of reduction of host response biomarkers with triclosan treatment. Triclosan significantly reduced levels of A. actinomycetemcomitans and P. gingivalis during induction of gingivitis. CONCLUSIONS: Triclosan reduced microbial levels during gingivitis development (ClinicalTrials.gov NCT01799226). PMID- 26820238 TI - Emerging role of long noncoding RNAs as regulators of innate immune cell development and inflammatory gene expression. AB - The innate immune system represents the first line of defense during infection and is initiated by the detection of conserved microbial products by germline encoded pattern recognition receptors (PRRs). Sensing through PRRs induces broad transcriptional changes that elicit powerful inflammatory responses. Tight regulation of these processes depends on multiple regulatory checkpoints, including noncoding RNA species such as microRNAs. In addition, long noncoding RNAs (lncRNAs) have recently gained attention as important regulators of gene expression acting through versatile interactions with DNA, RNA, or proteins. As such, these RNAs have a multitude of mechanisms to modulate gene expression. Here, we summarize recent advances in this rapidly moving and evolving field. We highlight the contribution of lncRNAs to both the development and activation of innate immune cells, whether it is in the nucleus, where lncRNAs alter the transcription of target genes through interaction with transcription factors, chromatin-modifying complexes or heterogeneous ribonucleoprotein complexes, or in the cytosol where they can control the stability of target mRNAs. In addition, we discuss experimental approaches required to comprehensively investigate the function of a candidate noncoding RNA locus, including loss-of-function approaches encompassing genomic deletions, RNA interference, locked nucleic acids, and various adaptions of the CRISPR/Cas9 technology. PMID- 26820242 TI - Tris(1,2-diphenylethylenediamine)cobalt(III) Complexes: Chiral Hydrogen Bond Donor Catalysts for Enantioselective alpha-Aminations of 1,3-Dicarbonyl Compounds. AB - The enantiopure salt Delta-[Co((S,S)-dpen)3](3+)2Cl(-)B(C6F5)4(-) is an effective hydrogen bond donor catalyst for additions of 1,3-dicarbonyl compounds to di-tert butyl azodicarboxylate in the presence of N-methylmorpholine (1.0:1.0:0.10) in CH3CN at 0 degrees C, as illustrated with educts derived from five- or six membered ring ketones (99-88% yields, >99-91% ee) and cycloheptanone (94%, 72% ee) as well as 2-cyanocyclopentanone (92%, 45% ee) and an acyclic system (98%, >99% ee). PMID- 26820240 TI - Integration of 3D Printed and Micropatterned Polycaprolactone Scaffolds for Guidance of Oriented Collagenous Tissue Formation In Vivo. AB - Scaffold design incorporating multiscale cues for clinically relevant, aligned tissue regeneration has potential to improve structural and functional integrity of multitissue interfaces. The objective of this preclinical study is to develop poly(epsilon-caprolactone) (PCL) scaffolds with mesoscale and microscale architectural cues specific to human ligament progenitor cells and assess their ability to form aligned bone-ligament-cementum complexes in vivo. PCL scaffolds are designed to integrate a 3D printed bone region with a micropatterned PCL thin film consisting of grooved pillars. The patterned film region is seeded with human ligament cells, fibroblasts transduced with bone morphogenetic protein-7 genes seeded within the bone region, and a tooth dentin segment positioned on the ligament region prior to subcutaneous implantation into a murine model. Results indicate increased tissue alignment in vivo using micropatterned PCL films, compared to random-porous PCL. At week 6, 30 MUm groove depth significantly enhances oriented collagen fiber thickness, overall cell alignment, and nuclear elongation relative to 10 MUm groove depth. This study demonstrates for the first time that scaffolds with combined hierarchical mesoscale and microscale features can align cells in vivo for oral tissue repair with potential for improving the regenerative response of other bone-ligament complexes. PMID- 26820241 TI - Relational coordination among home healthcare professions and goal attainment in nursing care. AB - AIM: To examine whether interprofessional coordination is related to goal attainment in home visit nursing care. METHODS: Self-administered questionnaire surveys were administered to home visit nursing agencies in Chiba Prefecture, Japan, from July to December 2014. Nurses evaluated their interprofessional coordination with professional groups (nursing colleague and managers, home doctors, care managers, home care workers, visiting therapists, day service and day care professionals, visiting bath professionals, and short stay professionals) using the Japanese version of the Relational Coordination Scale (RCS-J). Goal attainment across all clients during the most recent 3 months was measured with a rating scale ranging from incompletely attained (0) to completely attained (10). Data were analyzed with multivariate logistic regression analysis. RESULTS: A total of 83 nurses in 14 agencies responded, and data from 74 nurses were analyzed. The mean RCS-J and goal attainment scores were 3.59 (standard deviation = 0.47) and 6.51 (1.40), respectively. The RCS-J scores of the low and high goal attainment groups were 3.41 (0.46) and 3.73 (0.42), respectively. Multivariate logistic regression analysis revealed that RCS-J scores were positively associated with goal attainment (odds ratio, 5.71; 95% confidence interval, 1.65-19.79). CONCLUSION: The finding of this study suggest that well coordinated professionals may fulfill client needs better than poorly coordinated professionals do. Future research is needed to determine whether similar results are obtained in individual clients using a well-validated goal attainment scale. PMID- 26820243 TI - Mechanism of Photoinduced Metal-Free Atom Transfer Radical Polymerization: Experimental and Computational Studies. AB - Photoinduced metal-free atom transfer radical polymerization (ATRP) of methyl methacrylate was investigated using several phenothiazine derivatives and other related compounds as photoredox catalysts. The experiments show that all selected catalysts can be involved in the activation step, but not all of them participated efficiently in the deactivation step. The redox properties and the stability of radical cations derived from the catalysts were evaluated by cyclic voltammetry. Laser flash photolysis (LFP) was used to determine the lifetime and activity of photoexcited catalysts. Kinetic analysis of the activation reaction according to dissociative electron-transfer (DET) theory suggests that the activation occurs only with an excited state of catalyst. Density functional theory (DFT) calculations revealed the structures and stabilities of the radical cation intermediates as well as the reaction energy profiles of deactivation pathways with different photoredox catalysts. Both experiments and calculations suggest that the activation process undergoes a DET mechanism, while an associative electron transfer involving a termolecular encounter (the exact reverse of DET pathway) is favored in the deactivation process. This detailed study provides a deeper understanding of the chemical processes of metal-free ATRP that can aid the design of better catalytic systems. Additionally, this work elucidates several important common pathways involved in synthetically useful organic reactions catalyzed by photoredox catalysts. PMID- 26820244 TI - Possible Association Between Zika Virus Infection and Microcephaly - Brazil, 2015. AB - In early 2015, an outbreak of Zika virus, a flavivirus transmitted by Aedes mosquitoes, was identified in northeast Brazil, an area where dengue virus was also circulating. By September, reports of an increase in the number of infants born with microcephaly in Zika virus-affected areas began to emerge, and Zika virus RNA was identified in the amniotic fluid of two women whose fetuses had been found to have microcephaly by prenatal ultrasound. The Brazil Ministry of Health (MoH) established a task force to investigate the possible association of microcephaly with Zika virus infection during pregnancy and a registry for incident microcephaly cases (head circumference >=2 standard deviations [SD] below the mean for sex and gestational age at birth) and pregnancy outcomes among women suspected to have had Zika virus infection during pregnancy. Among a cohort of 35 infants with microcephaly born during August-October 2015 in eight of Brazil's 26 states and reported to the registry, the mothers of all 35 had lived in or visited Zika virus-affected areas during pregnancy, 25 (71%) infants had severe microcephaly (head circumference >3 SD below the mean for sex and gestational age), 17 (49%) had at least one neurologic abnormality, and among 27 infants who had neuroimaging studies, all had abnormalities. Tests for other congenital infections were negative. All infants had a lumbar puncture as part of the evaluation and cerebrospinal fluid (CSF) samples were sent to a reference laboratory in Brazil for Zika virus testing; results are not yet available. Further studies are needed to confirm the association of microcephaly with Zika virus infection during pregnancy and to understand any other adverse pregnancy outcomes associated with Zika virus infection. Pregnant women in Zika virus affected areas should protect themselves from mosquito bites by using air conditioning, screens, or nets when indoors, wearing long sleeves and pants, using permethrin-treated clothing and gear, and using insect repellents when outdoors. Pregnant and lactating women can use all U.S. Environmental Protection Agency (EPA)-registered insect repellents according to the product label. PMID- 26820245 TI - Concordance of Expert Consultation Diagnoses in the Review of Pelvic Washing Specimens. AB - OBJECTIVES: Cytologic specimens are routinely collected as part of gynecologic oncology surgery. Consultation cases often include cytology specimens. Outside diagnosis was compared to consultation diagnosis for cytopathology specimens that were part of larger oncologic cases. STUDY DESIGN: Gynecologic pathology consultation cases containing pelvic washing (PW) material were queried. Cases had major discordance if the diagnosis changed from negative to positive or vice versa, and minor discordance if an atypical diagnosis was changed to positive or negative or vice versa. RESULTS: Of 237 cases, 9 showed major discordance (4%), 29 showed minor discordance (12%) and the remaining 199 no discordance (84%). The 9 major discordance cases involved PWs from cases that were performed for ovarian pathology. Treatment would have changed in only 2 of the cases with major discordance. Of the minor discordance cases, 21/29 (72%) involved PW from ovarian cases and 8/29 (28%) were PW from uterine cases. CONCLUSIONS: Only a few cases showed major or minor discordance, and of those that were discordant, most involved ovarian specimens. Major discordance between original and consulting diagnoses would have changed treatment in only 2 cases. PMID- 26820246 TI - Characterization of malolactic bacteria isolated from Aosta Valley wines and evidence of psychrotrophy in some strains. AB - AIM: A survey on indigenous malolactic bacteria populations isolated from wines produced in 13 different wineries of Aosta Valley, the highest vine-growing area in Europe, was carried out in order to characterize the dominant strains in spontaneous malolactic fermentation (MLF) and to reveal the appearance of psychrotrophic ones. METHODS AND RESULTS: Fifty-four isolates were identify by ITS rDNA region analysis and partial sequencing of 16S rDNA gene: 80% were ascribed to Oenococcus oeni while the remaining 20% were attributed to Pediococcus damnosus species. The genetic diversity of 43 O. oeni isolates was investigated through PFGE analysis after ApaI and SfiI restriction: 28 different pulso-types were discriminated at a level of similarity of 90%. In general, the MLF was led by more than one strain simultaneously. No connection between genotype and grape variety or vine-training system or geographical site of isolation was observed. The histidine decarboxylase gene was not found in any isolate. Pediococci proved to be more resistant than oenococci to lysozyme. Three O. oeni strains (2A1, 6A2 and 11A4) were able to develop at 10 degrees C in Petit Rouge wine. CONCLUSIONS: Psychrotrophy is a phenotypic trait present in O. oeni species and it may be possible to select strains for the management of MLF in cold climate territories where this biologic transformation is very difficult to control. SIGNIFICANCE AND IMPACT OF THE STUDY: The natural emergence of strains able to perform the MLF at 10 degrees C in wine is a new finding, interesting because it confirms the ecological ability of O. oeni species to adapt itself to environmental conditions by strain phenotype variations. It can be also a starting point for more sustainable oenological practices, since it would be alternative to the conditioning systems of the tanks or of the wineries where they are costly in terms of investment and energy consumption. PMID- 26820248 TI - Isolated processing of geometric shapes and their corresponding shape words: Evidence from a delayed match-to-sample task. AB - Some theorists propose a domain-specific cognitive system dedicated to processing geometric information, but existence of this system remains debatable because of challenges in isolating geometric from linguistic and semantic processing. Recently, Sturz, Edwards, and Boyer (2014) developed a delayed match-to-sample task that presented a sample of a shape, shape word, or bidimensional stimulus composed of a shape and shape word. After a delay, participants identified the sample shape or the sample word by selecting between 2 shapes or 2 shape words. An asymmetrical pattern of interference emerged such that increased response times (RTs) and errors occurred in matching shape targets but not word targets. This was interpreted as shape words activating a semantic and spatial representation of shapes, but shapes only activating a spatial representation. The present experiments attempted to replicate and extend these results by manipulating figure-ground relations to contrast the original condition with an alternative to address an explanation based upon sample shape saliency (Experiment 1), by confirming the effectiveness of the saliency manipulation (Experiment 2), and by explicitly testing the assumption that shapes did not activate a semantic representation by reversing the sample-to-target matching criteria (Experiment 3). Experiment 1 replicated the asymmetrical pattern of results for both conditions, and Experiment 2 confirmed the saliency manipulation, which together undermine a pure saliency explanation. Experiment 3 produced a symmetrical pattern of results and suggests that the reversed matching criteria forced shapes to be processed in both a spatial and semantic fashion. These results provide support for a cognitive system dedicated to processing geometric information isolated from linguistic and semantic processing. (PsycINFO Database Record PMID- 26820247 TI - Balance the Carrier Mobility To Achieve High Performance Exciplex OLED Using a Triazine-Based Acceptor. AB - A star-shaped 1,3,5-triazine/cyano hybrid molecule CN-T2T was designed and synthesized as a new electron acceptor for efficient exciplex-based OLED emitter by mixing with a suitable electron donor (Tris-PCz). The CN-T2T/Tris-PCz exciplex emission shows a high PhiPL of 0.53 and a small DeltaET-S = -0.59 kcal/mol, affording intrinsically efficient fluorescence and highly efficient exciton up conversion. The large energy level offsets between Tris-PCz and CN-T2T and the balanced hole and electron mobility of Tris-PCz and CN-T2T, respectively, ensuring sufficient carrier density accumulated in the interface for efficient generation of exciplex excitons. Employing a facile device structure composed as ITO/4% ReO3:Tris-PCz (60 nm)/Tris-PCz (15 nm)/Tris-PCz:CN-T2T(1:1) (25 nm)/CN-T2T (50 nm)/Liq (0.5 nm)/Al (100 nm), in which the electron-hole capture is efficient without additional carrier injection barrier from donor (or acceptor) molecule and carriers mobilities are balanced in the emitting layer, leads to a highly efficient green exciplex OLED with external quantum efficiency (EQE) of 11.9%. The obtained EQE is 18% higher than that of a comparison device using an exciplex exhibiting a comparable PhiPL (0.50), in which TCTA shows similar energy levels but higher hole mobility as compared with Tris-PCz. Our results clearly indicate the significance of mobility balance in governing the efficiency of exciplex based OLED. Exploiting the Tris-PCz:CN-T2T exciplex as the host, we further demonstrated highly efficient yellow and red fluorescent OLEDs by doping 1 wt % Rubrene and DCJTB as emitter, achieving high EQE of 6.9 and 9.7%, respectively. PMID- 26820249 TI - Endogenous rhythms influence interpersonal synchrony. AB - Interpersonal synchrony, the temporal coordination of actions between individuals, is fundamental to social behaviors from conversational speech to dance and music-making. Animal models indicate constraints on synchrony that arise from endogenous rhythms: Intrinsic periodic behaviors or processes that continue in the absence of change in external stimulus conditions. We report evidence for a direct causal link between endogenous rhythms and interpersonal synchrony in a music performance task, which places high demands on temporal coordination. We first establish that endogenous rhythms, measured by spontaneous rates of individual performance, are stable within individuals across stimulus materials, limb movements, and time points. We then test a causal link between endogenous rhythms and interpersonal synchrony by pairing each musician with a partner who is either matched or mismatched in spontaneous rate and by measuring their joint behavior up to 1 year later. Partners performed melodies together, using either the same or different hands. Partners who were matched for spontaneous rate showed greater interpersonal synchrony in joint performance than mismatched partners, regardless of hand used. Endogenous rhythms offer potential to predict optimal group membership in joint behaviors that require temporal coordination. PMID- 26820251 TI - Zooming in on the cause of the perceptual load effect in the go/no-go paradigm. AB - Perceptual load theory (Lavie, 2005) claims that attentional capacity that is not used for the current task is allocated to irrelevant distractors. It predicts that if the attentional demands of the current task are high, distractor interference will be low. One particularly powerful demonstration of perceptual load effects on distractor processing relies on a go/no-go cue that is interpreted by either simple feature detection or feature conjunction (Lavie, 1995). However, a possible alternative interpretation of these effects is that the differential degree of distractor processing is caused by how broadly attention is allocated (attentional zoom) rather than to perceptual load. In 4 experiments, we show that when stimuli are arranged to equalize the extent of spatial attention across conditions, distractor interference varies little whether cues are defined by a simple feature or a conjunction, and that the typical perceptual load effect emerges only when attentional zoom can covary with perceptual load. These results suggest that attentional zoom can account for the differential degree of distractor processing traditionally attributed to perceptual load in the go/no-go paradigm. They also provide new insight into how different factors interact to control distractor interference. (PsycINFO Database Record PMID- 26820250 TI - Please say what this word is-Vowel-extrinsic normalization in the sensorimotor control of speech. AB - The extent to which the adaptive nature of speech perception influences the acoustic targets underlying speech production is not well understood. For example, listeners can rapidly accommodate to talker-dependent phonetic properties-a process known as vowel-extrinsic normalization-without altering their speech output. Recent evidence, however, shows that reinforcement-based learning in vowel perception alters the processing of speech auditory feedback, impacting sensorimotor control during vowel production. This suggests that more automatic and ubiquitous forms of perceptual plasticity, such as those characterizing perceptual talker normalization, may also impact the sensorimotor control of speech. To test this hypothesis, we set out to examine the possible effects of vowel-extrinsic normalization on experimental subjects' interpretation of their own speech outcomes. By combining a well-known manipulation of vowel extrinsic normalization with speech auditory-motor adaptation, we show that exposure to different vowel spectral properties subsequently alters auditory feedback processing during speech production, thereby influencing speech motor adaptation. These findings extend the scope of perceptual normalization processes to include auditory feedback and support the idea that naturally occurring adaptations found in speech perception impact speech production. (PsycINFO Database Record PMID- 26820252 TI - Protective effect of thymoquinone improves cardiovascular function, and attenuates oxidative stress, inflammation and apoptosis by mediating the PI3K/Akt pathway in diabetic rats. AB - Thymoquinone is the main active monomer extracted from black cumin and has anti inflammatory, antioxidant and anti-apoptotic functions. However, the protective effects of thymoquinone on cardiovascular function in diabetes remain to be fully elucidated. The present study aimed to investigate the molecular mechanisms underling the beneficial effects of thymoquinone on the cardiovascular function in streptozotocin-induced diabetes mellitus (DM) rats. Supplement thymoquinone may recover the insulin levels and body weight, inhibit blood glucose levels and reduce the heart rate in DM-induced rats. The results indicated that the heart, liver and lung to body weight ratios, in addition to the blood pressure levels, were similar for each experimental group. Treatment with thymoquinone significantly reduced oxidative stress damage, inhibited the increased endothelial nitric oxide synthase protein expression and suppressed the elevation of cyclooxygenase-2 levels in DM-induced rats. In addition, thymoquinone significantly suppressed the promotion of tumor necrosis factor-alpha and interleukin-6 levels in the DM-induced rats. Furthermore, administration of thymoquinone significantly reduced caspase-3 activity and the promotion of phosphorylated-protein kinase B (Akt) protein expression levels in DM-induced rats. These results suggest that the protective effect of thymoquinone improves cardiovascular function and attenuates oxidative stress, inflammation and apoptosis by mediating the phosphatidylinositol 3-kinase/Akt pathway in DM induced rats. PMID- 26820253 TI - Comparison of the inertial properties and forces required to initiate movement for three gait trainers. AB - The purpose of this study was to evaluate the inertial properties and forces required to initiate movement on two different surfaces in a sample of three commonly prescribed gait trainers. Tests were conducted in a laboratory setting to compare the Prime Engineering KidWalk, Rifton Pacer, and Snug Seat Mustang with and without a weighted anthropometric test dummy configured to the weight and proportions of a 4-year-old child. The Pacer was the lightest and the KidWalk the heaviest while footprints of the three gait trainers were similar. Weight was borne fairly evenly on the four casters of the Pacer and Mustang while 85% of the weight was borne on the large wheels of the mid-wheel drive KidWalk. These differences in frame style, wheel, and caster style and overall mass impact inertial properties and forces required to initiate movement. Test results suggest that initiation forces on tile were equivalent for the Pacer and KidWalk while the Mustang had the highest initiation force. Initiation forces on carpet were lowest for the KidWalk and highest for the Mustang. This initial study of inertia and movement initiation forces may provide added information for clinicians to consider when selecting a gait trainer for their clients. PMID- 26820254 TI - Gene expression profiling of microRNAs associated with UCA1 in bladder cancer cells. AB - Emerging evidence indicates that non-coding RNAs, such as lncRNAs and microRNAs, play important roles in diverse diseases, such as cancer, immune diseases and cardiovascular diseases. Interestingly, lncRNAs could directly or indirectly regulate the expression of miRNAs. However, the expression profiling of miRNAs associated with UCA1 in bladder cancer remains unknown. Here, we used Illumina deep sequencing to sequence miRNA libraries from both the UCA1 knockdown and normal high-expression 5637 cells. We identified 225 and 235 miRNAs expressed in 5637 cells of normal high-expression and knockdown of UCA1, respectively. Overall, expression of 75 miRNAs showed significant difference associated with UCA1, of which 38 were upregulated and 37 downregulated with UCA1 knockdown. GO analysis of the host target genes revealed that these aberrantly regulated miRNAs were involved in complex cellular pathways, including biological process, cellular component and molecular function. We selected 8 candidate miRNAs associated with UCA1 and predicted their targeted mRNAs, and found that p27kip1 was a crucial downstream molecule for these 8 miRNAs, especially for miR-196a. KEGG pathway analysis showed that PI3K-Akt signaling pathway was involved in regulating these 8 candidant miRNAs. Among these 8 candidant miRNAs, we observed the correlation among UCA1, miR-196a and the host target mRNA, p27kip1, in bladder cancer cells and tissues. UCA1 was upregulated by miR-196a and positively correlated with miR-196a, whereas UCA1 and miR-196a were negatively correlated with p27kip1, which was downregulated in bladder cancer patients. Thus, our findings provided valuable information on miRNAs associated with UCA1 in bladder cancer, which could be helpful to further explore the related genes and molecular networks fundamental in bladder cancer progression. PMID- 26820255 TI - Re-infection of the prion from the scrapie-infected cell line SMB-S15 in three strains of mice, CD1, C57BL/6 and Balb/c. AB - It is well known that the SMB-S15 cell line was originally established by cultures from the brains of mice affected by the Chandler scrapie strain, and this cell line may express PrPSc permanently. However, the infectivity of the S15 derived prions on experimental animals has not yet been well documented. In the present study, the cell lysates of SMB-S15 were intracerebrally inoculated into three different strains of mice, namely C57BL/6, Balb/c and CD1. Prion protein (PRNP) gene sequencing revealed the same encoded PrP proteins in the sequences of amino acids in the three strains of mice, in addition to a synonymous single nucleotide polymorphism (SNP) in CD1 mice. All infected mice developed typical experimental transmissible spongiform encephalopathies (TSEs) approximately six months post-infection. The clinical features of three infected mice were comparable. The pathogenic characteristics, such as the electrophoretic and glycosylation profiles and proteinase K (PK) resistance of PrPSc molecules, as well as the neuropathological characteristics, such as spongiform vacuolation, PrPSc deposits in cortex regions, astrogliosis and activated microglia, were also similar in all three strains of infected mice. However, PrPSc deposits in the cerebellums of CD1 mice were significantly fewer, which was linked with the observation that lower numbers of CD1 mice presented cerebellum-associated symptoms. Successive inoculation of the individual strains of mice with brain homogenates from the infected mice also induced typical experimental scrapie. The data in the present study thus confirm that the prion agent in SMB-S15 cells causes stable infectivity in different types of mice with distinct phenotypes after long-term propagation in vitro. The present study also provides further scrapie rodent models, which may be used in further studies. PMID- 26820256 TI - Safety and efficacy of hybrid energy and trifractional technologies in the treatment of acne scars: An open-label clinical trial. AB - INTRODUCTION: This study determines the safety and efficacy of a novel device- Surgen that utilizes hybrid energy (HE) technology and trifractional (TF) technology in the treatment of acne scars in Filipino patients. METHODS: Open label clinical trial on eight subjects who underwent 4 weekly HE treatments followed by 2 TF treatments spaced 3 weeks apart. Efficacy was evaluated by dermatologists' (investigator and two blinded dermatologists) and patients' assessment and grading of post-treatment digital photographs. Subjects also reported level of satisfaction and comfort. Adverse events were recorded. RESULTS: Dermatologists' grading of acne scars improvement--58.3% of subjects showed slight to moderate improvement, 8.3% showed marked improvement, and 33.3% was graded as unchanged after HE treatments. After 2 additional TF treatments grades improved further, with 37.5% showing mild to moderate improvement, 37.5% showing marked improvement, and 25% graded as unchanged. Dermatologist's scoring using the global acne scoring system resulted in improvement of 75% of patients after 4 HE sessions and 100% after TF treatments. Subjects' grading showed a similar trend: 75% of subjects reported that they were satisfied and 25% slightly satisfied after the complete protocol. CONCLUSION: A treatment protocol combining HE and TF technology is safe, effective, and comfortable in the treatment of acne scars. PMID- 26820257 TI - From risk reduction to implementation: Addressing the opioid epidemic and continued challenges to our field. PMID- 26820258 TI - Chemical composition and antioxidant, antibacterial activity of Cirsium rivulare (Jacq) All. roots. AB - The mixture of three phytosterols (campesterol, stigmasterol and beta sitosterol), beta-sitosterol 3-O-glucoside and syringin were isolated from hexane and methanol extract of Cirsium rivulare roots after chromatographic separation. The main component of the source was syringin which was obtained with the yield 0.08% of the dry source. In hexane extract, the qualitative and quantitative composition of fatty acids was determined. The predominant component was linoleic acid (23.31 mg/g of extract). The extracts showed antioxidant activity. The ability to scavenge DPPH* free radical was in correlation with appointed total phenol content. The not-defatted methanolic extract was the most active. Hexane and defatted methanol extracts showed moderate antibacterial activity against G(+) and G(-) strains with MIC and MBC ranged from 25 to 200 MUg/mL. PMID- 26820259 TI - Protective effect of Spirulina platensis against cell damage and apoptosis in hepatic tissue caused by high fat diet. AB - Spirulina platensis is a microalga that may be a source of antioxidants that can reduce body fat deposition. Consumption of a high fat diet produces elevated blood lipid levels, inflammation and apoptosis. We investigated the possible effects of S. platensis on the blood lipid profile, and liver inflammation and apoptosis in rats fed a high fat diet. Sixty-four young male rats were divided into eight equal groups. The control group was fed a basic diet. The experimental groups were fed a diet for 60 days that was prepared by mixing variable amounts of 43% vegetable oil and 10% cholesterol with or without 3% S. platensis mixed with the basal diet. Blood and liver tissue samples were collected from each animal. Serum samples were used to analyze lipid parameters, total antioxidant status and total oxidant status. iNOS and eNOS were determined by immunohistochemistry. TUNEL staining was used to detect apoptosis to investigate a possible connection between inflammation and apoptosis in the liver tissue. The relations between fat deposition and liver degeneration were assessed by Sirius red staining and alpha-smooth muscle actin immunostaining. S. platensis reduced serum HDL-C, LDL-C and triglyceride, increased HDL-C levels in rats fed a high fat diet to near control levels, and reduced iNOS levels and increased eNOS levels in the liver tissue compared to vegetable oil and cholesterol treated groups. The apoptotic index was reduced in the groups that were fed a high fat or a basic diet when supplemented with S. platensis. PMID- 26820260 TI - High Prevalence and Incidence of HIV and HCV Among New Injecting Drug Users With a Large Proportion of Migrants--Is Prevention Failing? AB - OBJECTIVES: The aim of this study was to assess differences in the prevalence of HIV and HCV infection and associated risk factors between new (injecting for <=5 years) and long-term injectors and to estimate HIV/HCV incidence among new injectors. METHODS: Cross-sectional study among people who inject drugs (PWID) who attended harm reduction centers in Catalonia in 2010-11. Anonymous questionnaires and oral fluid samples were collected. Poisson regression models were applied to determine the association between HIV/HCV infection and risk factors. RESULTS: Of the 761 participants, 21.4% were new injectors. New injectors were younger than long-term injectors (mean age = 31.6 vs. 37.8) and were more likely to be immigrants (59.0% vs. 33.4%). HIV and HCV prevalence was 20.6% and 59.4% among new injectors, and estimated HIV and HCV incidence 8.7 and 25.1 /100 person-years, respectively. Among new injectors, HIV infection was associated with homelessness (PR = 3.10) and reporting a previous sexually transmitted infection (PR = 1.79). Reporting front/backloading (PR = 1.33) and daily injection (PR = 1.35) were risk-factors for HCV infection. For long-term injectors, HIV risk factors were: having shared syringes (PR = 1.85), having injected cocaine (PR = 1.38), reporting front/backloading (PR = 1.30) and ever having been in prison (PR = 2.03). CONCLUSION: A large proportion of PWID in Catalonia are new injectors, a subgroup with a high level of both sexual and parenteral exposure and a high incidence rate of HIV/ HCV infections. It is important to improve early diagnosis of these infections among this group, in particular among migrants. To identify and address risk factors for homelessness PWID should be a priority. PMID- 26820261 TI - Ultraviolet light-emitting diode irradiation-induced cell death in HL-60 human leukemia cells in vitro. AB - Ultraviolet (UV) radiation is considered to be a potent cell-damaging agent in various cell lineages; however, the effect of UV light-emitting diode (LED) irradiation on human cells remains unclear. The aim of the present study was to examine the effect of UV LED irradiation emitting at 280 nm on cultured HL-60 human leukemia cells, and to explore the underlying mechanisms. HL-60 cells were irradiated with UV LED (8, 15, 30 and 60 J/m2) and incubated for 2 h after irradiation. The rates of cell proliferation and apoptosis, the cell cycle profiles and the mRNA expression of B-cell lymphoma 2 (Bcl-2) were detected using cell counting kit-8, multicaspase assays, propidium iodide staining and reverse transcription-quantitative polymerase chain reaction, respectively. The results showed that UV LED irradiation (8-60 J/m2) inhibited the proliferation of HL-60 cells in a dose-dependent manner. UV LED at 8-30 J/m2 induced dose-dependent apoptosis and G0/G1 cell cycle arrest, and inhibited the expression of Bcl-2 mRNA, while UV LED at 60 J/m2 induced necrosis. In conclusion, 280 nm UV LED irradiation inhibits proliferation and induces apoptosis and necrosis in cultured HL-60 cells. In addition, the cell cycle arrest at the G0/G1 phase and the downregulation of Bcl-2 mRNA expression were shown to be involved in UV LED induced apoptosis. PMID- 26820262 TI - Bisphenol A: Targeting metabolic tissues. AB - The prevalence of obesity, metabolic syndrome and type 2 diabetes has dramatically increased worldwide over the last few decades. Although genetic predisposition and lifestyle factors like decreased physical activity and energy dense diet are well-known factors in the pathophysiology of these conditions, accumulating evidence suggests that the increase in endocrine disrupting chemicals (EDCs) in the environment also explains a substantial part of the incidence of these metabolic diseases. Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. Most people are exposed to it daily by consuming food and beverages into which BPA has leached from polycarbonate containers, including reusable bottles and baby bottles. Although initially considered to be a weak environmental estrogen, BPA may be similar in potency to 17beta-estradiol in stimulating cellular responses, especially at low but environmentally relevant doses (nM), as more recent studies have demonstrated. In this review, we summarize both epidemiological evidence and in vivo experimental data that point to an association between BPA exposure and the induction of insulin resistance and/or disruption of pancreatic beta cell function and/or obesity. We then discuss the in vitro data and explain the potential mechanisms involved in the metabolic disorders observed after BPA exposure. PMID- 26820263 TI - Respiration in spiders (Araneae). AB - Spiders (Araneae) are unique regarding their respiratory system: they are the only animal group that breathe simultaneously with lungs and tracheae. Looking at the physiology of respiration the existence of tracheae plays an important role in spiders with a well-developed tracheal system. Other factors as sex, life time, type of prey capture and the high ability to gain energy anaerobically influence the resting and the active metabolic rate intensely. Most spiders have metabolic rates that are much lower than expected from body mass; but especially those with two pairs of lungs. Males normally have higher resting rates than females; spiders that are less evolved and possess a cribellum have lower metabolic rates than higher evolved species. Freely hunting spiders show a higher energy turnover than spiders hunting with a web. Spiders that live longer than 1 year will have lower metabolic rates than those species that die after 1 year in which development and reproduction must be completed. Lower temperatures and starvation, which most spiders can cope with, will decrease the metabolic rate as well. PMID- 26820264 TI - An atypical distribution of lactate dehydrogenase isoenzymes in the hooded seal (Cystophora cristata) brain may reflect a biochemical adaptation to diving. AB - The brains of some diving mammals can withstand periods of severe hypoxia without signs of deleterious effects. This may in part be due to an enhanced cerebral capacity for anaerobic energy production. Here, we have tested this hypothesis by comparing various parameters of the lactate dehydrogenase (LDH) in the brain of the hooded seal (Cystophora cristata) with those in the brains of the ferret (Mustela putorius furo) and mouse (Mus musculus). We found that mRNA and protein expression of lactate dehydrogenase a (LDHA) and lactate dehydrogenase b (LDHB), and also the LDH activity were significantly higher in the ferret brain than in brains of the hooded seal and the mouse (p < 0.0001). No conspicuous differences in the LDHA and LDHB sequences were observed. There was also no difference in the buffering capacities of the brains. Thus, an enhanced capacity for anaerobic energy production likely does not explain the higher hypoxia tolerance of the seal brain. However, the brain of the hooded seal had higher relative levels of LDHB isoenzymes (LDH1 and LDH2) compared to the non-diving mammals. Moreover, immunofluorescence studies showed more pronounced co-localization of LDHB and glial fibrillary acidic protein in the cortex of the hooded seal. Since LDHB isoenzymes primarily catalyze the conversion of lactate to pyruvate, this finding suggests that the contribution of astrocytes to the brain aerobic metabolism is higher in the hooded seal than in non-diving species. The cerebral tolerance of the hooded seal to hypoxia may therefore partly rely on different LDH isoenzymes distribution. PMID- 26820265 TI - Ocular Drug Distribution After Topical Administration: Population Pharmacokinetic Model in Rabbits. AB - BACKGROUND AND OBJECTIVE: When eye diseases are treated by topical administration, the success of treatment lies in the effective drug concentration in the target tissue. This is why the drug's pharmacokinetic, in the different substructures of the eye, needs to be explored more accurately during drug development. The aim of the present analysis was to describe by rabbit model, the distribution of a drug after ocular instillation in the selected eye tissues and fluids. METHODS: By a top-down population approach, we developed and validated a population pharmacokinetics (PopPK) model, using tissue concentrations (tear, naso-lacrymal duct, cornea and aqueous humor) of a new src tyrosine kinase inhibitor (FV-60165) in each anterior segment's tissue and fluid of the rabbit eye. Inter-individual variability was estimated and the impact of the formulation (solution or nanosuspension) was evaluated. RESULTS: The model structure selected for the eye is a 4-compartment model with the formulation as a significant covariate on the first-order rate constant between tears and the naso-lacrymal duct. The model showed a good predictive performance and may be used to estimate the concentration-time profiles after single or repeated administration, in each substructure of the eye for each animal included in the analysis. CONCLUSIONS: This analysis allowed describing the distribution of a drug in the different selected tissues and fluids in the rabbit's eyes after instillation of the prodrug as a solution or nanosuspension. PMID- 26820266 TI - Conservation Compromises: The MAB and the Legacy of the International Biological Program, 1964-1974. AB - This article looks at the International Biological Program (IBP) as the predecessor of UNESCO's well-known and highly successful Man and the Biosphere Programme (MAB). It argues that international conservation efforts of the 1970s, such as the MAB, must in fact be understood as a compound of two opposing attempts to reform international conservation in the 1960s. The scientific framework of the MAB has its origins in disputes between high-level conservationists affiliated with the International Union for the Conservation of Nature and Natural Resources (IUCN) about what the IBP meant for the future of conservation. Their respective visions entailed different ecological philosophies as much as diverging sets of political ideologies regarding the global implementation of conservation. Within the IBP's Conservation Section, one group propagated a universal systems approach to conservation with a centralized, technocratic management of nature and society by an elite group of independent scientific experts. Within IUCN, a second group based their notion of environmental expert roles on a more descriptive and local ecology of resource mapping as practiced by UNESCO. When the IBP came to an end in 1974, both groups' ecological philosophies played into the scientific framework underlying the MAB's World Network or Biosphere Reserves. The article argues that it is impossible to understand the course of conservation within the MAB without studying the dynamics and discourses between the two underlying expert groups and their respective visions for reforming conservation. PMID- 26820267 TI - Chemical Biology Probes from Advanced DNA-encoded Libraries. AB - The identification of bioactive compounds is a crucial step toward development of probes for chemical biology studies. Screening of DNA-encoded small molecule libraries (DELs) has emerged as a validated technology to interrogate vast chemical space. DELs consist of chimeric molecules composed of a low-molecular weight compound that is conjugated to a DNA identifier tag. They are screened as pooled libraries using selection to identify "hits." Screening of DELs has identified numerous bioactive compounds. Some of these molecules were instrumental in gaining a deeper understanding of biological systems. One of the main challenges in the field is the development of synthesis methodology for DELs. PMID- 26820268 TI - Preface. Controversies and Evolving Concepts in Critical Care. PMID- 26820269 TI - Too Little Oxygen: Ventilation, Prone Positioning, and Extracorporeal Membrane Oxygenation for Severe Hypoxemia. AB - Severe hypoxemia is associated with untoward outcomes in acute respiratory distress syndrome patients. Nevertheless, in and of itself, correction of hypoxemia is not an adequate surrogate outcome for mortality and clear evidence based targets for correction of hypoxemia remain to be determined. At present, clinical management is directed toward achieving sufficient oxygenation while minimizing toxicity of ventilator-induced lung injury. The gold standard remains lung-protective mechanical ventilation, using lower-tidal volumes and pressure limited ventilator titration. Notable progress in care includes further refinements in mechanical ventilation, consideration of salutatory effects of early prone positioning and neuromuscular blockade, and exploration of adjunctive extrapulmonary support with extracorporeal membrane oxygenation. This review focuses on three specific aspects: the evolving trend toward open lung ventilation, tempered by the recent cautionary experience with high-frequency oscillation ventilation; the evolution of prone positioning as a treatment for the most hypoxemic patients; and the continued future promise of extracorporeal support as a true rescue therapy. PMID- 26820270 TI - Too Much Oxygen: Hyperoxia and Oxygen Management in Mechanically Ventilated Patients. AB - Hyperoxia, or excess oxygen supplementation, prevails in the intensive care unit (ICU) without a beneficial effect and, in some instances, may cause harm. Recent interest and surge in clinical studies in mechanically ventilated critically ill patients has brought this to the attention of clinicians and researchers. Hyperoxia can cause alveolar injury, pulmonary edema, and subsequent systemic inflammatory response and is known to augment ventilator-associated lung injury. Liberal oxygenation practices are also associated with increased mortality in subsets of critically ill patients with post-cardiac arrest, stroke, and traumatic brain injury. Most clinicians agree that oxygen titration should be done and, with appropriate safeguards, lower oxygenation targets may be acceptable and possibly beneficial in many critically ill patients. However, this problem is often overlooked. The use of periodic reminders and decision support may facilitate implementation of more precise oxygen titration at the bedside of critically ill patients. For implementing practice change, studies involving education and guidance of all health care staff involved in oxygen management are critical. PMID- 26820271 TI - Less Is More in the ICU: Resuscitation, Oxygenation and Routine Tests. AB - The intensive care unit (ICU) was initially developed in the 1950s to treat patients who required invasive respiratory support and hemodynamic resuscitation. Since the beginning, ICU medicine has focused on maintaining sufficient arterial blood flow and oxygenation to provide adequate tissue oxygen delivery to forestall or reverse organ failure. Over time, ICU medicine became more intensive, with the administration of many diagnostic tests and monitors, invasive procedures, and treatments, often with scant evidence of benefit associated with them. An alternative perspective holds that ICU patients may represent a group of patients that is especially vulnerable to iatrogenic harm. We outline a case that presents common ICU dilemmas and discusses current data that propose that "less is more" when making key diagnostic or therapeutic choices in the ICU. Further, we assert that providers should skeptically consider common ICU interventions, trying to account for the potential unintended consequences of interventions. Finally, we suggest that the guiding principle of ICU medicine should be primum non nocere: in delicate situations, it may be better not to do something, or even to do nothing, rather than risk causing harm. PMID- 26820272 TI - How Cool It Is: Targeted Temperature Management for Brain Protection Post-Cardiac Arrest. AB - Neurological recovery often determines outcome in patients resuscitated after cardiac arrest. Temperature control as a neuroprotective strategy has become standard of care. The first randomized trials showing improved neurological outcomes in patients treated with hypothermia with a target temperature of 33 degrees C over a decade ago led to the inclusion of this intervention in practice guidelines and the broad adoption of hypothermia protocols across the world. More recently, large randomized trials showed no difference from targeting a temperature of 33 or 36 degrees C and no benefit from pre-hospital induction of hypothermia. Temperature control remains a crucial part of post-cardiac arrest care. However, the optimal temperature target, timing of induction, duration of temperature control, and speed of rewarming are unclear. Similarly, the value of targeted temperature management in cases of in-hospital arrest and non-shockable rhythms is unknown. This article reviews the neuroprotective mechanisms of hypothermia, the evidence supporting targeted temperature management after cardiac resuscitation, areas of persistent uncertainty and controversy, and future research directions. PMID- 26820273 TI - Balance between Hyperinflammation and Immunosuppression in Sepsis. AB - Sepsis is a major cause of morbidity and mortality among hospitalized patients and the leading cause of death among patients admitted to intensive care units. The immune response in sepsis is characterized by the activation of both proinflammatory and anti-inflammatory pathways. These pathways are concurrent, starting early in the course of sepsis. Given the high burden of morbidity and mortality associated with sepsis, there is an increasing interest in immunomodulatory therapies targeted at improving outcomes in sepsis. This review will summarize current understanding about the balance between hyperinflammation and immunosuppression in sepsis and discuss the role of potential therapies to modulate these responses. PMID- 26820274 TI - What Is the Evidence for Harm of Neuromuscular Blockade and Corticosteroid Use in the Intensive Care Unit? AB - Neuromuscular blocking agents and corticosteroids are widely used in medicine and in particular in the intensive care unit (ICU). Neuromuscular blockade is commonly used to ease tracheal intubation, to optimize mechanical ventilation and oxygenation in acute respiratory disorders such as status asthmaticus and acute respiratory distress syndrome (ARDS), to prevent shivering during therapeutic hypothermia, and also in patients with elevated intracranial pressure. In the ICU, patients with sepsis, ARDS, community-acquired pneumonia, exacerbation of chronic obstructive pulmonary disease, severe asthma, or trauma may receive corticosteroids. It is not rare that ICU patients receive concomitantly neuromuscular blocking drugs and corticosteroids. Among the various serious adverse reactions to these drugs, secondary infection and ICU-acquired weakness may place a burden to the health-care system by resulting in substantial cost and long-term morbidity. Both superinfections and ICU-acquired paresis are more likely when high doses of fluorinated corticosteroids are combined with prolonged treatment with a long-acting non-depolarizing neuromuscular blocker. Modern ICU practices favor lower dose of corticosteroids and very short course of short acting curare for the management of sepsis or ARDS. Recent trials provided no evidence for increased risk of secondary infections or critical illness neuromyopathy in patients with sepsis or ARDS with the use of corticosteroids or neuromuscular blockers. PMID- 26820276 TI - Early Warning/Track-and-Trigger Systems to Detect Deterioration and Improve Outcomes in Hospitalized Patients. AB - As a global effort toward improving patient safety, a specific area of focus has been the early recognition and rapid intervention in deteriorating ward patients. This focus on "failure to rescue" has led to the construction of early warning/track-and-trigger systems. In this review article, we present a description of the data behind the creation and implementation of such systems, including multiple algorithms and strategies for deployment. Additionally, the strengths and weaknesses of the various systems and their evaluation in the literature are emphasized. Despite the limitations of the current literature, the potential benefit of these early warning/track-and-trigger systems to improve patient outcomes remains significant. PMID- 26820275 TI - Sweet Spot: Glucose Control in the Intensive Care Unit. AB - Hyperglycemia, hypoglycemia, and glycemic variability are all independently associated with morbidity and mortality of critically ill patients. A strategy aiming at normoglycemia (so-called tight glycemic control) could improve outcomes of critically ill patients, but results from randomized controlled trials of tight glycemic control are conflicting. Strict glycemic control is associated with an increased risk of hypoglycemia, which could offset the benefit of this intervention. Notably, the risk of hypoglycemia is not necessarily removed with less tight glucose control regimens. The best targets of blood glucose control in critically ill patients, therefore, remain a matter of debate. It should be realized that blood glucose control is a complex intervention, consisting of many critical aspects that have the potential to affect its efficacy and safety. Efficacy, and in particular safety, of blood glucose control could still improve. First, glucose algorithms could overcome the lack of knowledge and skills of nursing staff when they are less experienced in safe and efficient blood glucose control. Several computerized glucose control algorithms have been developed over recent years, but they all need clinical validation. Also, the workload induced by such algorithms should be evaluated. Second, continuous blood glucose monitoring has the potential to improve safety and efficacy. Until recently, blood glucose levels were monitored manually using point-of-care devices with significant inaccuracies. Various continuous monitoring systems have been developed, but studies testing their accuracies and usefulness in an intensive care unit setting are highly needed. PMID- 26820277 TI - Improving the Patient Handoff Process in the Intensive Care Unit: Keys to Reducing Errors and Improving Outcomes. AB - Patient handoffs are highly variable and error prone. They have been recognized as a major health care challenge. Patients in the intensive care unit are particularly vulnerable due to their complex clinical history and the critical nature of their condition. Given a general movement from traditional long call to shift schedules, the number of patient handoffs will likely continue to increase. Optimization of the handoff process has become even more critical to ensure patient safety. In this review, we reflect on the importance of the handoff process, review common errors, identify barriers and challenges, and propose different methods to improving the handoff process. The purpose of this article is to examine the overall scope of the problem; provide the most up-to-date evidence on the handoff process; and identify ways to perform handoffs in an accurate, safe, and efficient manner to provide high-quality patient care. The direction of future research is also proposed. PMID- 26820278 TI - Who Should Be at the Bedside 24/7: Doctors, Families, Nurses? AB - Critical illness does not keep to regular, daytime business hours; we must provide high-quality care and support for intensive care unit (ICU) patients 24 hours per day, 7 days per week. Whether this mandates the presence of similar numbers and types of personnel throughout all hours of the day, however, has been the subject of much debate and substantial research. In this article, we review the available literature on the consequences of having three groups of care providers at a patient's bedside overnight: physicians, visitors, and nurses. Though few of the studies on this topic are randomized and prospective, several themes have emerged from the existing data. First, there is dramatic variation in practice between and within countries. Second, the weight of evidence does not indicate that patient outcomes are improved by having an intensivist present overnight in ICUs that are staffed by intensivists during the daytime hours. Third, although visitation is highly restricted in many ICUs-out of concerns for disruption of care and a negative physiological or psychological impact on patients-the available data suggest that patients and their families generally benefit from open visitation policies. And finally, although there is little debate that nurses are (and should be) available in the ICU 24/7, existing data do not provide much of a consensus about the details. Uncertainties include whether outcomes are better when each nurse is assigned only one patient (or, more generally, the optimal patient:nurse ratio), who these nurses should be (e.g., registered nurses vs. other personnel), and what their roles should entail (e.g., managing ventilators). As such, we cannot yet identify the optimal overnight nurse staffing strategy. What is clear is that the critical care community needs more and better data to further define these aspects of the relationship between ICU structure and ICU outcomes. PMID- 26820279 TI - Adapting the ABCDEF Bundle to Meet the Needs of Patients Requiring Prolonged Mechanical Ventilation in the Long-Term Acute Care Hospital Setting: Historical Perspectives and Practical Implications. AB - When robust clinical trials are lacking, clinicians are often forced to extrapolate safe and effective evidence-based interventions from one patient care setting to another. This article is about such an extrapolation from the intensive care unit (ICU) to the long-term acute care hospital (LTACH) setting. Chronic critical illness is an emerging, disabling, costly, and yet relatively silent epidemic that is central to both of these settings. The number of chronically critically ill patients requiring prolonged mechanical ventilation is expected to reach unprecedented levels over the next decade. Despite the prevalence, numerous distressing symptoms, and exceptionally poor outcomes associated with chronic critical illness, to date there is very limited scientific evidence available to guide the care and management of this exceptionally vulnerable population, particularly in LTACHs. Recent studies conducted in the traditional ICU setting suggest interprofessional, multicomponent strategies aimed at effectively assessing, preventing, and managing pain, agitation, delirium, and weakness, such as the ABCDEF bundle, may play an important role in the recovery of the chronically critically ill. This article reviews what is known about the chronically critically ill, provide readers with some important historical perspectives on the ABCDEF bundle, and address some controversies and practical implications of adopting the ABCDEF bundle into the everyday care of patients requiring prolonged mechanical ventilation in the LTACH setting. We believe developing new and better ways of addressing both the science and organizational aspects of managing the common and distressing symptoms associated with chronic critical illness and prolonged mechanical ventilation will ultimately improve the quality of life for the many patients and families admitted to LTACHs annually. PMID- 26820280 TI - Early Psychological Therapy in Critical Illness. AB - Survivors of critical illness often experience long-lasting impairments in mental, cognitive, and physical functioning. Acute stress reactions and delusional memories appear to play an important role in psychological morbidity following critical illness, and few interventions exist to address these symptoms. This review elucidates acute psychological stressors experienced by the critically ill. The effects of psychological stress and state of mind on disease are discussed using examples from the non-intensive care unit (ICU) literature, including a review of placebo and nocebo effects. After reviewing the effect of the mind on both psychological and physiological outcomes, we then focus on the role of memories-including their malleable nature and the consequences of false memories. Memory may play a role in the genesis of subsequent psychological trauma. Traumatic memories may begin forming even before the patient arrives in the ICU and during their state of unconsciousness in the ICU. Hence, practical interventions for redirecting patients' thoughts, such as positive suggestion techniques and actively involving patients in the treatment process as early as possible, are worthy of further investigation. PMID- 26820281 TI - Erratum to: Asbestos-Related Lung Cancer and Malignant Mesothelioma of the Pleura: Selected Current Issues (Semin Respir Crit Care Med 2015;36(3):334-346). PMID- 26820282 TI - Do pathologists agree on how to diagnose takotsubo cardiomyopathy? PMID- 26820283 TI - A novel, comprehensive, and reproducible porcine model for determining the timing of bruises in forensic pathology. AB - PURPOSE: Calculating the timing of bruises is crucial in forensic pathology but is a challenging discipline in both human and veterinary medicine. A mechanical device for inflicting bruises in pigs was developed and validated, and the pathological reactions in the bruises were studied over time in order to identify gross and histological parameters that may be useful in determining the age of a bruise. METHODS: The mechanical device was able to apply a single reproducible stroke with a plastic tube that was equivalent to being struck by a man. In each of 10 anesthetized pigs, four strokes that resulted in bruises were inflicted on the back. In addition, 2 control pigs were included in the study. The pigs were euthanized consecutively from 1 to 10 h after the infliction of bruises. Following gross evaluation, skin, and muscle tissues were sampled for histology. RESULTS: Grossly, the bruises appeared uniform and identical to the tramline bruises seen in humans and pigs subjected to blunt trauma. Histologically, the number of neutrophils in the subcutis, the number of macrophages in the muscle tissue, and the localization of neutrophils and macrophages in muscle tissue showed a time-dependent response. Combining these parameters, bruises could be grouped as being either less than 4 h old or between 4 and 10 h of age. Gross lesions and changes in the epidermis and dermis were inconclusive with respect to time determination. CONCLUSIONS: The model was reproducible and resembled forensic cases of bruises in pigs and humans. Therefore, the histological parameters are suitable for age determination of bruises in pigs and likely also in humans. PMID- 26820285 TI - Validation of temperature methods for the estimation of pre-appearance interval in carrion insects. AB - The pre-appearance interval (PAI) is an interval preceding appearance of an insect taxon on a cadaver. It decreases with an increase in temperature in several forensically-relevant insects. Therefore, forensic entomologists developed temperature methods for the estimation of PAI. In the current study these methods were tested in the case of adult and larval Necrodes littoralis (Coleoptera: Silphidae), adult and larval Creophilus maxillosus (Coleoptera: Staphylinidae), adult Necrobia rufipes (Coleoptera: Cleridae), adult Saprinus semistriatus (Coleoptera: Histeridae) and adult Stearibia nigriceps (Diptera: Piophilidae). Moreover, factors affecting accuracy of estimation and techniques for the approximation and correction of predictor temperature were studied using results of a multi-year pig carcass study. It was demonstrated that temperature methods outperform conventional methods. The accuracy of estimation was strongly related to the quality of the temperature model for PAI and the quality of temperature data used for the estimation. Models for larval stage performed better than models for adult stage. Mean temperature for the average seasonal PAI was a good initial approximation of predictor temperature. Moreover, iterative estimation of PAI was found to effectively correct predictor temperature, although some pitfalls were identified in this respect. Implications for the estimation of PAI are discussed. PMID- 26820284 TI - An approach to iatrogenic deaths. AB - Iatrogenic deaths are a concern for patients, physicians, and public health specialists. Most medicolegal investigation jurisdictions in the United States have the legal authority and mandate to investigate deaths associated with diagnostic/therapeutic procedures. Given the decreasing trends of autopsies performed in U.S. hospitals, forensic pathologists are likely to take on an even greater role in investigating these deaths. This is an overview and forensic pathological approach to fatal complications due to diagnostic and therapeutic medical events. PMID- 26820286 TI - Management of Hyperleukocytosis. AB - OPINION STATEMENT: Hyperleukocytosis has a high morbidity index. The involvement of the respiratory or central nervous system and the metabolic derangements accompanying tumor lysis are responsible for early mortality. Standard care for acute hyperleukocytosis must include cytoreduction, proper supportive care, and prevention of tumor lysis. Hydration, alkalization, allopurinol, or urate oxidase should be started immediately. In patients with low platelet count of less than 20,000/mm(3), platelet transfusions should be given to prevent cerebral hemorrhage, as platelets do not add substantially to blood viscosity. Packed red blood cells must be given with caution as they can significantly increase blood viscosity. If the patient is hemodynamically stable, packed red transfusions should be planned when the hemoglobin level is less than 7-8 g/dl, avoiding post transfusional levels above 10 g/dl. Coagulation abnormalities should be corrected. Leukapheresis has been advocated to correct metabolic abnormalities and to decrease viscosity by reducing the peripheral white blood count. However, leukapheresis may fail to decrease the leukocyte count substantially or may achieve only a transient tumor bulk reduction. The procedure is generally well tolerated but can involve problems such as the need for anticoagulation or difficulty of access, and limited availability in many institutions.Specific antileukemic therapy must be initiated as soon as life-threatening complications have been corrected as it remains the first-line treatment of hyperleukocytosis. PMID- 26820287 TI - The Role of Surgery in Metastatic Gastrointestinal Stromal Tumors. AB - OPINION STATEMENT: Gastrointestinal stromal tumors (GISTs) are the most common sarcomas and mesenchymal neoplasms of the gastrointestinal tract. Macroscopically complete (R0/R1) resection is the standard treatment for localized resectable GIST with adjuvant imatinib therapy recommended for patients with intermediate or high-risk disease. In patients with advanced unresectable or metastatic GIST, imatinib has significantly improved outcomes. However, while most patients achieve partial response (PR) or stable disease (SD) on imatinib (with maximal response typically seen by 6 months on treatment), approximately half will develop secondary resistance by 2 years. Available data suggest that cytoreductive surgery may be considered in patients with metastatic GIST who respond to imatinib, particularly if a R0/R1 resection is achieved. The benefit of surgery in patients with focal tumor progression on imatinib is unclear, but may be considered. Patients with multifocal progression undergoing surgery generally have poor outcomes. Thus, surgery should be considered in patients with metastatic GIST whose disease responds to imatinib with a goal of performing R0/R1 resection. Optimal timing of surgery is unclear but should be considered between 6 months and 2 years after starting imatinib. Although surgery in patients with metastatic GIST treated with sunitinib is feasible, incomplete resections are common, complication rates are high, and survival benefit is unclear. Therefore, a careful multidisciplinary consultation is required to determine optimal treatment options on a case-by-case basis. Finally, patients with metastatic GIST should resume tyrosine kinase inhibitor treatment postoperatively. PMID- 26820288 TI - Health-Related Quality of Life After Spine Surgery for Primary Bone Tumour. AB - OPINION STATEMENT: Treatment of primary bone tumours (PBT) of the spine is complex, often involving numerous surgical and oncology disciplines. Surgical en bloc resection with oncologically appropriate margins is the modality of choice when treating malignant PBT. En bloc resection with wide or marginal margins appears to offer better local and systemic control of the disease. This type of surgical resection can also be considered when treating benign aggressive tumours such as aneurysmal bone cyst, giant cell tumour and osteoblastoma. Although these surgeries respect oncologic principles, significant morbidity and mortality are associated. Adverse event collection is highly variable in the literature and mostly from retrospective studies. Wound complication, neurologic deficit and significant blood loss are encountered with surgical resection of PBT of the mobile spine and especially, the sacrum. The adverse event profile of these surgeries is high even in experienced quaternary referral centres. Therefore, primary spinal tumour resection is best performed in experienced centre with adequate multidisciplinary support. Furthermore, prospective and systematic adverse event data collection should be developed to ensure accurate data. The impact of such extensive and potentially impairment producing procedures on health-related quality of life (HRQOL) is another critically valuable piece of information in the era of shared treatment decision making. At the present time, there is paucity of published data regarding HRQOL following these surgeries. Nonetheless, in theory, it seems that health-related quality of life after surgery for PBT is acceptable given the curative intent of the treatment. However, a decision-making process should be tailored to each patient and his or her expectations. Comprehensive discussions should be held preoperatively with the patient, family and other related allied health professionals if the informed consent and decision-making process is to be optimal. PMID- 26820290 TI - Erratum to: Effect of mold type, diameter, and uncured composite removal method on depth of cure. PMID- 26820289 TI - Current Systemic Treatment Options for Tenosynovial Giant Cell Tumor/Pigmented Villonodular Synovitis: Targeting the CSF1/CSF1R Axis. AB - OPINION STATEMENT: Adequate surgical resection remains the treatment of choice for tenosyovial giant cell tumor (TGCT). However, diffuse type TGCT (D-TGCT) is more difficult to resect and has a higher rate of recurrence (up to 50 %), which is often multiple. D-TGCT is rarely lethal and only rare cases of metastases have been described. Nevertheless, patients might have a significant decline in their quality of life due to multiple operations, which may sometimes result in a partial loss of function of the affected joint and may also be associated with perioperative morbidity and secondary arthrosis. As of today, no systemic treatment is approved for this rare disease. The aims of systemic therapy in the context of a non-lethal tumor are to reduce surgical morbidity and to preserve function and patient quality of life. Because TGCT is associated with characteristic cytogenetic abnormalities resulting in the overexpression of CSF1, systemic therapies targeting the CSF1/CSF1R axis (imatinib, nilotinib, emactuzumab, and PLX3397) have been tested in patients with locally advanced or relapsed D-TGCT. The more recent and more specific CSF1R inhibitors have shown a very interesting clinical activity with acceptable toxicity in early phase trials. These results will need to be confirmed in larger, ideally randomized, trials. But the high rate of clinical and functional improvement seen in some patients with advanced D-TGCT, often after multiple operations, suggests that these inhibitors will likely have a role in the management of patients with an inoperable disease; the definition of "inoperable TGCT" still requires refinement to reach a consensus. Another point that will need to be addressed is that of "the optimal duration of therapy" for these patients. Indeed, we and others have observed often prolonged clinical benefit and symptomatic relief even after treatment was stopped, with both monoclonal antibodies and tyrosine kinase inhibitors. Responses were observed very early on with emactuzumab and PLX3397, and patients experienced significant symptom improvement within a few weeks of starting therapy (2-4 weeks). Another possible application of CSF1R inhibitors could be used either as a preoperative or postoperative therapy for patients with operable TGCT. However, we currently lack sufficient follow-up to adequately address these questions which will each require specific trial designs. Overall, the striking clinical activity of CSF1R specific inhibitors in TGCT has created great enthusiasm among clinicians, and further development of these agents is clearly medically needed. Nevertheless, further investigations are necessary to validate those treatments and assess how to best incorporate them among other treatment modalities into the overall therapeutic strategy for a given patient. PMID- 26820291 TI - A micro-computed tomography assessment of the efficacy of rotary and reciprocating techniques for filling material removal in root canal retreatment. AB - OBJECTIVES: The aim of this study was to compare the efficacy of rotary and reciprocating techniques for removing filling material from root canals, using micro-computed tomography (micro-CT) imaging. MATERIALS AND METHODS: The distal root canals of 42 human mandibular molars were instrumented with hand files up to size 40 according to a step-down technique and obturated with gutta-percha and an epoxy resin-based sealer using Tagger's hybrid technique. Teeth were divided into six groups (n = 7) according to the instruments used for removal of filling material: group PTUR (Protaper Universal Retreatment), group W40 (WaveOne 40.08), group R40 (Reciproc 40.06), group R50 (Reciproc 50.05), group W25/W40 (WaveOne 25.08/40.08), and group R25/R40/R50 (Reciproc 25.08/40.06/50.05). Teeth were scanned with a micro-CT device before and after use of the instruments to calculate the percentage of remaining filling material. Data were compared using one-way ANOVA and Fisher's LSD test at 5 % significance level. RESULTS: The mean percentage of remaining filling material was significantly lower when canals were retreated with the set of instruments R25/R40/R50 and single instruments W40 and R50 compared with the set of instruments W25/W40 (P < 0.05), which promoted material compaction in the apical region. CONCLUSION: None of the retreatment techniques removed the root fillings completely. PTUR instruments performed equally effective regarding filling removal compared with W40, R40, R50, W25/W40, and R25/R40/R50. For WaveOne, the use of a single instrument (size 40, taper 0.08) was more effective in removing filling material, while for Reciproc showed similar cleaning ability using single instrument or combination of instruments. CLINICAL RELEVANCE: The results of this in vitro study provide consistent information on filling material removal capacity of mechanized systems during retreatment at the different root canal thirds. PMID- 26820292 TI - Potentially inappropriate prescribing in two populations with differing socio economic profiles: a cross-sectional database study using the PROMPT criteria. AB - PURPOSE: The purpose of this study is to establish the prevalence of potentially inappropriate prescribing (PIP) in middle-aged adults (45-64 years) in two populations with differing socio-economic profiles, and to investigate factors associated with PIP, using the PROMPT (PRescribing Optimally in Middle-aged People's Treatments) criteria. METHODS: A retrospective cross-sectional study was conducted using 2012 data from the Enhanced Prescribing Database (EPD), covering the full population in Northern Ireland and the Health Services Executive Primary Care Reimbursement Service (HSE-PCRS) database, covering the most socio economically deprived third of the population in this age group in the Republic of Ireland. The prevalence for each PROMPT criterion and overall prevalence of PIP were calculated. Logistic regression was used to investigate the association between PIP and gender, age group and polypharmacy. RESULTS: This study included 441,925 patients from the EPD and 309,748 patients from the HSE-PCRS database. Polypharmacy was common in both datasets (46.7 % in the HSE-PCRS and 20.3 % in the EPD). The prevalence of PIP was 42.9 % (95%CI 42.7, 43.1) in the HSE-PCRS and 21.1 % (95%CI 21.0, 21.2) in the EPD. Age group, female gender and polypharmacy were significantly associated with PIP in both populations (p < 0.05) and polypharmacy had the strongest association. CONCLUSIONS: PIP is common amongst middle-aged people with the risk of PIP increasing with polypharmacy. Differences in the prevalence of polypharmacy and PIP between the two populations may relate to heterogeneity in healthcare services and different socio-economic profiles, with higher rates of multimorbidity and associated polypharmacy in more deprived groups. PMID- 26820293 TI - Addiction of lung cancer cells to GOF p53 is promoted by up-regulation of epidermal growth factor receptor through multiple contacts with p53 transactivation domain and promoter. AB - Human lung cancers harboring gain-of-function (GOF) p53 alleles express higher levels of the epidermal growth factor receptor (EGFR). We demonstrate that a number of GOF p53 alleles directly upregulate EGFR. Knock-down of p53 in lung cancer cells lowers EGFR expression and reduces tumorigenicity and other GOF p53 properties. However, addiction of lung cancer cells to GOF p53 can be compensated by overexpressing EGFR, suggesting that EGFR plays a critical role in addiction. Chromatin immunoprecipitation (ChIP) using lung cancer cells expressing GOF p53 alleles showed that GOF p53 localized to the EGFR promoter. The sequence where GOF p53 is found to interact by ChIP seq can act as a GOF p53 response element. The presence of GOF p53 on the EGFR promoter increased histone H3 acetylation, indicating a mechanism whereby GOF p53 enhances chromatin opening for improved access to transcription factors (TFs). ChIP and ChIP-re-ChIP with p53, Sp1 and CBP histone acetylase (HAT) antibodies revealed docking of GOF p53 on Sp1, leading to increased binding of Sp1 and CBP to the EGFR promoter. Up-regulation of EGFR can occur via GOF p53 contact at other novel sites in the EGFR promoter even when TAD-I is inactivated; these sites are used by both intact and TAD-I mutated GOF p53 and might reflect redundancy in GOF p53 mechanisms for EGFR transactivation. Thus, the oncogenic action of GOF p53 in lung cancer is highly dependent on transactivation of the EGFR promoter via a novel transcriptional mechanism involving coordinated interactions of TFs, HATs and GOF p53. PMID- 26820295 TI - Identification of quinazoline compounds as novel potent inhibitors of Wnt/beta catenin signaling in colorectal cancer cells. AB - The Wnt/beta-catenin signaling pathway is critical for the initiation and progression of most colon cancers, and has emerged as one of the most promising targets for colorectal cancer chemoprevention and treatment. In this study, we have discovered a structurally related series of quinazolines as potent inhibitors of Wnt/beta-catenin signaling in colorectal cancer cells harboring mutations in CTNNB1 or APC. We showed that the quinazoline leads suppressed Wnt/beta-catenin signaling without altering the level of beta-catenin protein in colorectal cancer cells, suggesting that they act on the downstream elements of the pathway. Moreover, the quinazoline leads displayed potent anticancer activities with IC50 values between 4.9 and 17.4 MUM in colorectal cancer cells. Importantly, we also found that a structurally related quinazoline lacking inhibitory effect on Wnt/beta-catenin signaling was unable to suppress colorectal cancer cell proliferation. Together, these results suggest that the quinazoline lead compounds identified in this study have therapeutic potential for the prevention and treatment of colorectal cancer. PMID- 26820296 TI - Blocking the survival of the nastiest by HSP90 inhibition. AB - It is now recognised that genetic, epigenetic and phenotypic heterogeneity within individual human cancers is responsible for therapeutic resistance - knowledge that is having a profound impact on current thinking and experimentation. There has been concern that molecularly targeted therapy is doomed to failure, with resistant clones emerging in response to the Darwinian selective pressure of any drug treatment. However, two studies have shown that the evolution of drug resistance can be restrained by co-administration of a pharmacologic inhibitor of the HSP90 molecular chaperone. PMID- 26820294 TI - Downregulation of TFAM inhibits the tumorigenesis of non-small cell lung cancer by activating ROS-mediated JNK/p38MAPK signaling and reducing cellular bioenergetics. AB - Mitochondrial transcription factor A (TFAM) is essential for the replication, transcription and maintenance of mitochondrial DNA (mtDNA). The role of TFAM in non-small cell lung cancer (NSCLC) remains largely unknown. Herein, we report that downregulation of TFAM in NSCLC cells resulted in cell cycle arrest at G1 phase and significantly blocked NSCLC cell growth and migration through the activation of reactive oxygen species (ROS)-induced c-Jun amino-terminal kinase(JNK)/p38 MAPK signaling and decreased cellular bioenergetics. We further found that TFAM downregulation in NSCLC cells led to increased apoptotic cell death and enhanced the sensitivity of NSCLC cells to cisplatin. Tissue microarray (TMA) data showed that elevated expression of TFAM was related to the histological grade and TNM stage of NSCLC patients. We also demonstrated that TFAM is an independent prognostic factor for overall survival of NSCLC patients. Taken together, our findings suggest that TFAM could serve as a potential diagnostic biomarker and molecular target for the treatment of NSCLC, as well as for prediction of the effectiveness of chemotherapy. PMID- 26820297 TI - Circadian rhythms of body temperature and locomotor activity in aging BALB/c mice: early and late life span predictors. AB - Impairment of one or more parameters of circadian rhythms (CR) of body temperature (BT) and locomotor activity (LMA) are considered among the hallmarks of mammalian aging. These alterations are frequently used as markers for imminent death in laboratory mice. However, there are still contradictory data for particular strains and it is also uncertain which changes might predict senescence changes later in life, including the force of mortality. In the present paper we use telemetry to study LMA and CR of BT during aging of BALB/c mice. At our knowledge this is the first time that CR of BT and LMA are investigated in this strain in a range of age covering the whole lifespan, from young adult up to very old age. CR of BT was analyzed with a cosine model using a cross sectional approach and follow-up measurements. The results show that BT, LMA, amplitude, goodness-of-fit (GoF) to circadian cycle of temperature decrease with different shapes during chronological age. Moreover, we found that the % change of amplitude and BT in early life (5-19 months) can predict the remaining lifespan of the mice. Later in life (22-32 months), best predictors are single measurements of LMA and GoF. The results of this study also offer potential measures to rapidly identifying freely unrestrained mice with the worst longitudinal outcome and against which existing or novel biomarkers and treatments may be assessed. PMID- 26820298 TI - Penis morphology in a Burmese amber harvestman. AB - A unique specimen of the fossil harvestman Halitherses grimaldii Giribet and Dunlop, 2005 (Arachnida: Opiliones) from the Cretaceous (ca. 99 Ma) Burmese amber of Myanmar reveals a fully extended penis. This is the first record of a male copulatory organ of this nature preserved in amber and is of special importance due to the age of the deposit. The penis has a slender, distally flattened truncus, a spatulate heart-shaped glans and a short distal stylus, twisted at the tip. In living harvestmen, the penis yields crucial characters for their systematics. Male genital morphology in H. grimaldii appears to be unique among the wider Dyspnoi clade to which this fossil belongs. The large eyes in the fossil differ markedly from other members of the subfamily Ortholasmatinae to which H. grimaldii was originally referred. Based on recent data, it has been argued that large eyes may be plesiomorphic for Palpatores (i.e. the suborders Eupnoi and Dyspnoi), potentially rendering this character plesiomorphic for the fossil too. Thus, the unique structure of the penis seen here, and the probable lack of diaphanous teeth, present in all other extant non-acropsopilionid Dyspnoi, suggest that H. grimaldii represents a new, extinct family of large-eyed dyspnoid harvestmen, Halithersidae fam. nov.; a higher taxon in amber diagnosed here on both somatic and genital characters. PMID- 26820299 TI - First description of a fossil chamaeleonid from Greece and its relevance for the European biogeographic history of the group. AB - The fossil record of Chamaeleonidae is very scarce and any new specimen is therefore considered important for our understanding of the evolutionary and biogeographic history of the group. New specimens from the early Miocene of Aliveri (Evia Island), Greece constitute the only fossils of these lizards from southeastern Europe. Skull roofing material is tentatively attributed to the Czech species Chamaeleo cf. andrusovi, revealing a range extension for this taxon, whereas tooth-bearing elements are described as indeterminate chamaeleonids. The Aliveri fossils rank well among the oldest known reptiles from Greece, provide evidence for the dispersal routes of chameleons out of Africa towards the European continent and, additionally, imply strong affinities with coeval chamaeleonids from Central Europe. PMID- 26820300 TI - Laparoscopic parenchymal preserving hepatic resections in semiprone position for tumors located in the posterosuperior segments. AB - INTRODUCTION: All patients who underwent laparoscopic liver resections in the posterosuperior segments (LPSS) at our center were positioned in semiprone since August 2011. The aims of this study were to assess differences in perioperative outcomes between laparoscopic left lateral sectionectomies (LLLS) performed in supine position and LPSS in semiprone position. METHODS: We reviewed our prospectively collected database of all liver resections performed between January 2012 and January 2015. LLLS and LPSS were compared with respect to demographics and perioperative outcomes. RESULTS: Forty-five patients underwent LLLS (n = 20) or LPSS (n = 25). There were no differences in patient demographics or tumor diameter (p = 0.946). There were no conversions. Pringle maneuver was not used in both groups. There was no difference in peroperative central venous pressure (p = 0.511). The median operative time in the LLLS group was 100 min (60 260) and 160 min (95-270) in the LPSS group (p = 0.002) with median intraoperative blood loss in the LLLS group of 50 ml (0-550) versus a larger 150 ml (50-700) (p = 0.010) for patients receiving LPSS. No patients required transfusion. Intraoperative and postoperative complication rates were similar in both groups. Median hospital stay was 6 days in both groups (p = 0.554). CONCLUSION: LPSS in semiprone can be performed with similar clinical outcomes as a minor laparoscopic liver resection except for longer operative time and larger intraoperative blood loss without the need for transfusion. PMID- 26820301 TI - The Influence of Cuff Width, Sex, and Race on Arterial Occlusion: Implications for Blood Flow Restriction Research. AB - PURPOSE: The main aim of this study was to examine differences in upper arm arterial occlusion pressure (AOP) between three different cuff widths and how individual characteristics influence this. Additional aims of the study were to investigate differences in AOP due to sex and race and to create regression equations that estimate AOP for each cuff width. METHODS: Two hundred and forty nine participants (males n = 102; females n = 147) visited the laboratory once for measurement of arm length, arm circumference, and resting brachial systolic (bSBP) and diastolic blood pressure (bDBP). Next, each cuff was applied to the upper arm and inflated until a Doppler probe placed at the radial artery no longer detected blood flow. The minimum inflation pressure that caused cessation of blood flow was determined to be the AOP. RESULTS: Differences in AOP were observed between cuff widths (p < 0.001). The 5-cm-wide cuff required the greatest inflation pressure [145 (19) mmHg], followed by the 10 cm [123 (13) mmHg], and 12-cm-wide cuff [120 (12) mmHg]. A model encompassing arm circumference, bSBP, arm length, bDBP, and sex explained the most variance in AOP for each cuff (5 cm, R (2) = 0.651; 10 cm, R (2) = 0.570; 12 cm, R (2) = 0.557). However, arm circumference explained the most unique variance for each cuff. When separated by sex, males required greater pressures. Additionally, after controlling for sex, it was found that non-Hispanic Blacks required greater pressures compared with Whites. The regression equations for each cuff width are as follows: 5 cm (mmHg) = 2.926 (arm circumference) + 1.002 (bSBP) - 0.428 (arm length) + 0.213 (bDBP) + 12.668 (sex) - 68.493; 10 cm (mmHg) = 1.545 (arm circumference) + 0.722 (bSBP) - 0.235 (arm length) + 0.205 (bDBP) + 6.378 (sex) - 15.918; 12 cm (mmHg) = 1.393 (arm circumference) + 0.710 (bSBP) - 0.294 (arm length) + 0.164 (bDBP) + 6.419 (sex) - 8.752. CONCLUSIONS: The AOP is dependent upon cuff width, highlighting the need for authors to report cuff width and consider the impact it has on restriction. Participant characteristics, especially arm circumference, should be considered when applying this blood flow restriction pressure. Lastly, both sex and race have an impact on AOP, although it is not presently known how meaningful this difference is. PMID- 26820302 TI - The distinct C-terminal acidic domains of HMGB proteins are functionally relevant in Schistosoma mansoni. AB - The Schistosoma mansoni High Mobility Group Box (HMGB) proteins SmHMGB1, SmHMGB2 and SmHMGB3 share highly conserved HMG box DNA binding domains but have significantly different C-terminal acidic tails. Here, we used three full-length and tailless forms of the S. mansoni HMGB proteins to examine the functional roles of their acidic tails. DNA binding assays revealed that the different lengths of the acidic tails among the three SmHMGB proteins significantly and distinctively influenced their DNA transactions. Spectroscopic analyses indicated that the longest acidic tail of SmHMGB3 contributes to the structural stabilisation of this protein. Using immunohistochemical analysis, we showed distinct patterns of SmHMGB1, SmHMGB2 and SmHMGB3 expression in different tissues of adult worms. RNA interference approaches indicated a role for SmHMGB2 and SmHMGB3 in the reproductive system of female worms, whereas for SmHMGB1 no clear phenotype was observed. Schistosome HMGB proteins can be phosphorylated, acetylated and methylated. Importantly, the acetylation and methylation of schistosome HMGBs were greatly enhanced upon removal of the acidic tail. These data support the notion that the C-terminal acidic tails dictate the differences in the structure, expression and function of schistosome HMGB proteins. PMID- 26820303 TI - Seasonality in the proportions of domestic cats shedding Toxoplasma gondii or Hammondia hammondi oocysts is associated with climatic factors. AB - A previous study on domestic cats in Germany and neighbouring countries suggested seasonality in shedding Toxoplasma gondii oocysts. The aim of the present study was to elucidate whether this seasonality in shedding could be explained by climatic effects and whether differences between years in the proportions of cats shedding oocysts could also be explained by climatic factors. To this end, a long term study over a period of 55 months on domestic cats for T. gondii and Hammondia hammondi oocysts was performed and the results compared with climatic data. Using species-specific PCR, T. gondii oocysts were identified in 0.14% (84/61,224) and H. hammondi in 0.10% (61/61,224) of the samples. Toxoplasma gondii oocysts were predominantly observed from summer to autumn, while H. hammondi oocysts were mainly found during autumn and winter. In statistical analyses using climatic data, even differences in parasitological findings between years could be partially modelled using monthly temperature, North Atlantic Oscillation indices and precipitation. Of the three climatic variables analysed, precipitation as an explanatory variable had the lowest impact in the statistical models while those taking only temperature and North Atlantic Oscillation indices into account were sufficiently predictive. Interestingly, time lags between the climatic event and the parasitological findings had to be implemented in all models. For T. gondii, North Atlantic Oscillation indices with a time lag of 7 months and temperature with a time lag of 2 months had the best predictive value. In contrast, temperature (with a time lag of 6 months) and the interaction of precipitation (with a time lag of 5 months) and North Atlantic Oscillation indices (with a time lag of 11 months) were optimal for predicting the seasonality of H. hammondi. These results suggest prominent differences in the life cycles of the two closely related parasites. Previous findings showed that H. hammondi lack avian hosts, in contrast to T. gondii, and the coincidence in the periods of high abundance of birds and high proportions of cats shedding T. gondii suggest that birds may play an important role in the epidemiology of this infection. The result that North Atlantic Oscillation index is an important variable in modelling variations in the proportion of cats shedding T. gondii and H. hammondi over the year is an indication that global warming may also influence the infection risk of animals and humans with T. gondii and H. hammondi. The findings have important implications for planning epidemiological studies and for estimating the risk of human infection. PMID- 26820304 TI - Association of the Ratio of Early Mitral Inflow Velocity to the Global Diastolic Strain Rate with a Rapid Renal Function Decline in Atrial Fibrillation. AB - The ratio of early mitral inflow velocity (E) to the global diastolic strain rate (E'sr) has been correlated with left ventricular filling pressure and predicts adverse cardiac outcomes in atrial fibrillation (AF). The relationship between the E/E'sr ratio and renal outcomes in AF has not been evaluated. This study examined the ability of the E/E'sr ratio in predicting progression to the renal endpoint, which is defined as a >= 25% decline in the estimated glomerular filtration rate in patients with AF. Comprehensive echocardiography was performed on 149 patients with persistent AF, and E'sr was assessed from three standard apical views using the index beat method. During a median follow-up period of 2.3 years, 63 patients (42.3%) were reaching the renal endpoint. Multivariate analysis showed that an increased E/E'sr ratio (per 10 cm) (hazard ratio, 1.230; 95% confidence interval, 1.088 to 1.391; p = 0.001) was associated with an increased renal endpoint. In a direct comparison, the E/E'sr ratio outperformed the ratio of E to early diastolic mitral annular velocity (E') in predicting progression to the renal endpoint in both univariate and multivariate models (p <= 0.039). Moreover, adding the E/E'sr ratio to a clinical model and echocardiographic parameters provided an additional benefit in the prediction of progression to the renal endpoint (p = 0.006). The E/E'sr ratio is a useful parameter and is stronger than the E/E' ratio in predicting the progression to the renal endpoint, and it may offer an additional prognostic benefit over conventional clinical and echocardiographic parameters in patients with AF. PMID- 26820306 TI - Purification and Characterization of a Novel Cold-Active Lipase from the Yeast Candida zeylanoides. AB - Cold-active lipases have attracted attention in recent years due to their potential applications in reactions requiring lower temperatures. Both bacterial and fungal lipases have been investigated, each having distinct advantages for particular applications. Among yeasts, cold-active lipases from the genera Candida, Yarrowia, Rhodotorula, and Pichia have been reported. In this paper, biosynthesis and properties of a novel cold-active lipase from Candida zeylanoides isolated from refrigerated poultry meat are described. Heat sterilized olive oil was found to be the best lipase biosynthesis inducer, while nonionic detergents were not effective. The enzyme was purified to homogeneity using hydrophobic chromatography and its enzymatic properties were tested. Pure enzyme activity at 7 degrees C was about 60% of the maximal activity at 27 degrees C. The enzyme had rather good activity at higher temperatures, as well. Optimal pH of pure lipase was between 7.3 and 8.2, while the enzyme from the crude extract had an optimum pH of about 9.0. The enzyme was sensitive to high ionic strength and lost most of its activity at high salt concentrations. Due to the described properties, cold-active C. zeylanoides lipase has comparative advantages to most similar enzymes with technological applications and may have potential to become an industrially important enzyme. PMID- 26820305 TI - Effect of Broccoli Sprouts and Live Attenuated Influenza Virus on Peripheral Blood Natural Killer Cells: A Randomized, Double-Blind Study. AB - Enhancing antiviral host defense responses through nutritional supplementation would be an attractive strategy in the fight against influenza. Using inoculation with live attenuated influenza virus (LAIV) as an infection model, we have recently shown that ingestion of sulforaphane-containing broccoli sprout homogenates (BSH) reduces markers of viral load in the nose. To investigate the systemic effects of short-term BSH supplementation in the context of LAIV inoculation, we examined peripheral blood immune cell populations in non-smoking subjects from this study, with a particular focus on NK cells. We carried out a randomized, double-blinded, placebo-controlled study measuring the effects of BSH (N = 13) or placebo (alfalfa sprout homogenate, ASH; N = 16) on peripheral blood mononuclear cell responses to a standard nasal vaccine dose of LAIV in healthy volunteers. Blood was drawn prior to (day-1) and post (day2, day21) LAIV inoculation and analyzed for neutrophils, monocytes, macrophages, T cells, NKT cells, and NK cells. In addition, NK cells were enriched, stimulated, and assessed for surface markers, intracellular markers, and cytotoxic potential by flow cytometry. Overall, LAIV significantly reduced NKT (day2 and day21) and T cell (day2) populations. LAIV decreased NK cell CD56 and CD158b expression, while significantly increasing CD16 expression and cytotoxic potential (on day2). BSH supplementation further increased LAIV-induced granzyme B production (day2) in NK cells compared to ASH and in the BSH group granzyme B levels appeared to be negatively associated with influenza RNA levels in nasal lavage fluid cells. We conclude that nasal influenza infection may induce complex changes in peripheral blood NK cell activation, and that BSH increases virus-induced peripheral blood NK cell granzyme B production, an effect that may be important for enhanced antiviral defense responses. TRIAL REGISTRATION: ClinicalTrials.gov NCT01269723. PMID- 26820307 TI - The Subjective Health Horizon Questionnaire (SHH-Q): Assessing Future Time Perspectives for Facets of an Active Lifestyle. AB - BACKGROUND: A wider subjective time horizon is assumed to be positively associated with longevity and vitality. In particular, a lifestyle with exposure to novel and varied information is considered beneficial for healthy cognitive aging. At present, measures that specifically assess individuals' perceived temporal extension to engage in active lifestyles in the future are not available. OBJECTIVES: We introduce and validate a new self-report measure, the Subjective Health Horizon Questionnaire (SHH-Q). The SHH-Q assesses individuals' future time perspectives in relation to four interrelated but distinct lifestyle dimensions: (1) novelty-oriented exploration (Novelty), (2) bodily fitness (Body), (3) work goals (Work), and (4) goals in life (Life Goals). The present study aims at: (a) validating the hypothesized factor structure of the SHH-Q, according to which the SHH-Q consists of four interrelated but distinct subscales, and (b) testing the hypothesis that the Novelty and Body subscales of the SHH-Q show positive and selective associations with markers of cognition and somatic health, respectively. METHODS: Using structural equation modeling, we analyzed data from 1,371 healthy individuals (51% women) with a mean age of 70.1 years (SD = 3.6) who participated in the Berlin Aging Study II (BASE-II) and completed the SHH-Q. RESULTS: As predicted, the SHH-Q formed four correlated but distinct subscales: (1) Novelty, (2) Body, (3) Work, and (4) Life Goals. Greater self-reported future novelty orientation was associated with higher current memory performance, and greater future expectations regarding bodily fitness with better current metabolic status. CONCLUSION: The SHH-Q reliably assesses individual differences in four distinct dimensions of future time perspective. Two of these dimensions, Novelty and Body, show differential associations with cognitive status and somatic health. The SHH-Q may serve as a tool to assess how different facets of future time perspective relate to somatic health, cognition, motivation, and affect, and may help to identify the socioeconomic and individual antecedents, correlates, and consequences of an active lifestyle. PMID- 26820308 TI - Three Cases of Bullous Pemphigoid Associated with Dipeptidyl Peptidase-4 Inhibitors - One due to Linagliptin. AB - BACKGROUND: Bullous pemphigoid (BP) is an acquired subepidermal autoimmune blistering disease in which there are humoral and cellular responses against the BP180 and BP230 antigens. Dipeptidyl peptidase (DPP)-4 inhibitors enhance endogenous glucagon peptide-1 and glucose-dependent insulinotropic polypeptide secretion with food intake, which leads to insulin secretion, as well as to the reduction of glucagon secretion. Recently, several cases of DPP-4 inhibitor associated BP have been reported. OBJECTIVES: To report 3 cases of DPP-4 inhibitor-associated BP, one of which is due to linagliptin use, as well as to review all currently published cases of DPP-4 inhibitor-associated BP. CASE REPORTS: Three patients diagnosed with BP at our department showed a clear temporal relationship between the introduction of DPP-4 for the treatment of diabetes and the onset of BP. One case was due to linagliptin use, while the other 2 cases were due to an association with vildagliptin-metformin use. CONCLUSIONS: This is the first report of linagliptin-associated BP. Furthermore, 2 other cases of vildagliptin-associated BP are reported. PMID- 26820309 TI - Fluoroscopy-Free Pulmonary Vein Isolation in Patients with Atrial Fibrillation and a Patent Foramen Ovale Using Solely an Electroanatomic Mapping System. AB - INTRODUCTION: The advent of electroanatomical mapping (EAM) systems for pulmonary vein isolation (PVI) has dramatically decreased radiation exposure. However, the need for some fluoroscopy remains for obtaining left atrial (LA) access. The aim was to test the feasibility of fluoroscopy-free PVI in patients with atrial fibrillation (AF) and a patent foramen ovale (PFO) guided solely by an EAM system. METHODS: Consecutive patients with AF undergoing PVI and documented PFO were studied. An EAM-guided approach without fluoroscopy and ultrasound was used. After completing the map of the right atrium, the superior vena cava and the coronary sinus, a catheter pull-down to the PFO was performed allowing LA access. The map of the LA and subsequent PVI was also performed without fluoroscopy. RESULTS: 30 patients [age 61+/-12 years, 73% male, ejection fraction 0.64 (0.53 0.65), LA size in parasternal long axis 38+/-7 mm] undergoing PVI were included. The time required for right atrial mapping including transseptal crossing was 9+/ 4 minutes. Total procedure time was 127+/-37 minutes. Fluoroscopy-free PVI was feasible in 26/30 (87%) patients. In four patients, fluoroscopy was needed to access (n = 3) or to re-access (n = 1) the LA. In these four patients, total fluoroscopy time was 5+/-3 min and the DAP was 14.9+/-13.4 Gy*cm2. Single procedure success rate was 80% (24/30) after a median follow-up of 12 months. CONCLUSION: In patients with a documented PFO, completely fluoroscopy-free PVI is feasible in the vast majority of cases. PMID- 26820310 TI - Inhibitory Effect of Bridged Nucleosides on Thermus aquaticus DNA Polymerase and Insight into the Binding Interactions. AB - Modified nucleosides have the potential to inhibit DNA polymerases for the treatment of viral infections and cancer. With the hope of developing potent drug candidates by the modification of the 2',4'-position of the ribose with the inclusion of a bridge, efforts were focused on the inhibition of Taq DNA polymerase using quantitative real time PCR, and the results revealed the significant inhibitory effects of 2',4'-bridged thymidine nucleoside on the polymerase. Study on the mode of inhibition revealed the competitive mechanism with which the 2',4'-bridged thymidine operates. With a Ki value of 9.7 +/- 1.1 MUM, the 2',4'-bridged thymidine proved to be a very promising inhibitor. Additionally, docking analysis showed that all the nucleosides including 2',4' bridged thymidine were able to dock in the active site, indicating that the substrate analogs reflect a structural complementarity to the enzyme active site. The analysis also provided evidence that Asp610 was a key binding site for 2',4' bridged thymidine. Molecular dynamics (MD) simulations were performed to further understand the conformational variations of the binding. The root-mean-square deviation (RMSD) values for the peptide backbone of the enzyme and the nitrogenous base of the inhibitor stabilized within 0.8 and 0.2 ns, respectively. Furthermore, the MD analysis indicates substantial conformational change in the ligand (inhibitor) as the nitrogenous base rotated anticlockwise with respect to the sugar moiety, complemented by the formation of several new hydrogen bonds where Arg587 served as a pivot axis for binding formation. In conclusion, the active site inhibition of Taq DNA polymerase by 2',4'-bridged thymidine suggests the potential of bridged nucleosides as drug candidates. PMID- 26820311 TI - Oil Adulteration Identification by Hyperspectral Imaging Using QHM and ICA. AB - To investigate the feasibility of identification of qualified and adulterated oil product using hyperspectral imaging(HIS) technique, a novel feature set based on quantized histogram matrix (QHM) and feature selection method using improved kernel independent component analysis (iKICA) is proposed for HSI. We use UV and Halogen excitations in this study. Region of interest(ROI) of hyperspectral images of 256 oil samples from four varieties are obtained within the spectral region of 400-720nm. Radiation indexes extracted from each ROI are used as feature vectors. These indexes are individual band radiation index (RI), difference of consecutive spectral band radiation index (DRI), ratio of consecutive spectral band radiation index (RRI) and normalized DRI (NDRI). Another set of features called quantized histogram matrix (QHM) are extracted by applying quantization on the image histogram from these features. Based on these feature sets, improved kernel independent component analysis (iKICA) is used to select significant features. For comparison, algorithms such as plus L reduce R (plusLrR), Fisher, multidimensional scaling (MDS), independent component analysis (ICA), and principle component analysis (PCA) are also used to select the most significant wavelengths or features. Support vector machine (SVM) is used as the classifier. Experimental results show that the proposed methods are able to obtain robust and better classification performance with fewer number of spectral bands and simplify the design of computer vision systems. PMID- 26820312 TI - Correction: Targeted Next-Generation Sequencing for Clinical Diagnosis of 561 Mendelian Diseases. AB - [This corrects the article DOI: 10.1371/journal.pone.0133636.]. PMID- 26820313 TI - Targeted Next-Generation Sequencing Identifies a Recurrent Mutation in MCPH1 Associating with Hereditary Breast Cancer Susceptibility. AB - Breast cancer is strongly influenced by hereditary risk factors, a majority of which still remain unknown. Here, we performed a targeted next-generation sequencing of 796 genes implicated in DNA repair in 189 Finnish breast cancer cases with indication of hereditary disease susceptibility and focused the analysis on protein truncating mutations. A recurrent heterozygous mutation (c.904_916del, p.Arg304ValfsTer3) was identified in early DNA damage response gene, MCPH1, significantly associating with breast cancer susceptibility both in familial (5/145, 3.4%, P = 0.003, OR 8.3) and unselected cases (16/1150, 1.4%, P = 0.016, OR 3.3). A total of 21 mutation positive families were identified, of which one-third exhibited also brain tumors and/or sarcomas (P = 0.0007). Mutation carriers exhibited significant increase in genomic instability assessed by cytogenetic analysis for spontaneous chromosomal rearrangements in peripheral blood lymphocytes (P = 0.0007), suggesting an effect for MCPH1 haploinsufficiency on cancer susceptibility. Furthermore, 40% of the mutation carrier tumors exhibited loss of the wild-type allele. These findings collectively provide strong evidence for MCHP1 being a novel breast cancer susceptibility gene, which warrants further investigations in other populations. PMID- 26820315 TI - Open boundary molecular dynamics of sheared star-polymer melts. AB - Open boundary molecular dynamics (OBMD) simulations of a sheared star polymer melt under isothermal conditions are performed to study the rheology and molecular structure of the melt under a fixed normal load. Comparison is made with the standard molecular dynamics (MD) in periodic (closed) boxes at a fixed shear rate (using the SLLOD dynamics). The OBMD system exchanges mass and momentum with adjacent reservoirs (buffers) where the external pressure tensor is imposed. Insertion of molecules in the buffers is made feasible by implementing there a low resolution model (blob-molecules with soft effective interactions) and then using the adaptive resolution scheme (AdResS) to connect with the bulk MD. Straining with increasing shear stress induces melt expansion and a significantly different redistribution of pressure compared with the closed case. In the open sample, the shear viscosity is also a bit lowered but more stable against the viscous heating. At a given Weissenberg number, molecular deformations and material properties (recoverable shear strain and normal stress ratio) are found to be similar in both setups. We also study the modelling effect of normal and tangential friction between monomers implemented in a dissipative particle dynamics (DPD) thermostat. Interestingly, the tangential friction substantially enhances the elastic response of the melt due to a reduction of the kinetic stress viscous contribution. PMID- 26820314 TI - A Systematic Study of the Effect of Different Molecular Weights of Hyaluronic Acid on Mesenchymal Stromal Cell-Mediated Immunomodulation. AB - INTRODUCTION: Osteoarthritis (OA) is associated with chronic inflammation, and mesenchymal stromal cells (MSCs) have been shown to provide pain relief and reparative effects in clinical investigations. MSCs are often delivered with hyaluronic acid (HA), although the combined mechanism of action is not fully understood; we thus investigated the immunomodulatory effects of combining MSCs with different molecular weights (MW) of HA. METHODS: HAs with MWs of 1.6 MDa (hHA), 150 kDa or 7.5 kDa, were added to MSCs alone or MSC-immune cell co cultures. Gene expression analyses, flow cytometry and cytokine measurements were assessed to determine the effect of HAs on the MSC interactions with immune cells. RESULTS: MSCs in the presence of HAs, in both normal and lymphocyte conditioned medium, showed negligible changes in gene expression. While addition of hHA resulted in increased proliferation of activated lymphocytes, both in the presence and absence of MSCs, the overall combined effect was a more regulated, homeostatic one; this was supported by higher ratios of secreted IL10/IFNgamma and IL10/IL2, in lymphocyte cultures, than with lower MW HAs or no HA, both in the presence and absence of MSCs. In addition, examination of monocyte-derived macrophages showed an increased M2 macrophage frequency (CD14+CD163+CD206+) in the presence of hHA, both with and without MSCs. CONCLUSIONS: hHA produces a less pro-inflammatory environment than lower MW HAs. Moreover, combining hHA with MSCs has an additive effect on the MSC-mediated immunomodulation, suggestive of a more potent combination treatment modality for OA. PMID- 26820316 TI - Integration of nanomaterials for colorimetric immunoassays with improved performance: a functional perspective. AB - The boom of nanotechnology has yielded exciting developments in designing new kinds of colorimetric immunoassays. These nanomaterial-associated immunoassays have shown great potential for clinical translation and a number of them have already been implemented for testing patient samples from the clinics. Different from most reviews where researchers typically focus on a specific type of nanomaterial or describe assays based on the types of materials, we classify these assays by the function of nanomaterials, focusing on reviewing the distinct phenomenon of nanomaterials and how these properties are utilized to overcome limitations faced by traditional colorimetric immunoassays. We also discuss the challenges and give our perspectives in this field. PMID- 26820317 TI - Canadian Association of General Surgeons position statement: recommendations for surgeons with blood-borne communicable diseases. AB - SUMMARY: The potential for transmission of hematogenously transmitted pathogens during exposure-prone procedures is a clinically important concern to both patients and surgeons. There is inconsistency among regulatory bodies in Canada regarding the management of infection risk among surgeons, particularly with regard to screening and the postexposure management of infected surgeons. The Canadian Association of General Surgeons commissioned a task force to review the evidence regarding the management of blood-borne pathogens and transmission risk during surgical procedures. The results of this review indicate a need for several jurisdictions to update their guidelines to reflect current evidence based practices. PMID- 26820318 TI - Very early initiation of chemical venous thromboembolism prophylaxis after blunt solid organ injury is safe. AB - BACKGROUND: The optimal timing of initiating low-molecular weight heparin (LMWH) in patients who have undergone nonoperative management (NOM) of blunt solid organ injuries (SOIs) remains controversial. We describe the safety of early initiation of chemical venous thromboembolism (VTE) prophylaxis among patients undergoing NOM of blunt SOIs. METHODS: We retrospectively studied severely injured adults who sustained blunt SOI without significant intracranial hemorrhage and underwent an initial NOM at a Canadian lead trauma hospital between 2010 and 2014. Safety was assessed based on failure of NOM, defined as the need for operative intervention, in patients who received early (< 48 h) or late LMWH (>= 48 h, or early discharge [< 72 h] without LMWH). RESULTS: We included 162 patients in our analysis. Most were men (69%), and the average age was 42 +/- 18 years. The median injury severity score was 17, and splenic injuries were most common (97 [60%], median grade 2), followed by liver (57 [35%], median grade 2) and kidney injuries (31 [19%], median grade 1). Combined injuries were present in 14% of patients. A total of 78 (48%) patients received early LMWH, while 84 (52%) received late LMWH. The groups differed only in percent of high-grade splenic injury (14% v. 32%). Overall 2% of patients failed NOM, none after receiving LMWH. Semielective angiography was performed in 23 (14%) patients. The overall rate of confirmed VTE on imaging was 1.9%. CONCLUSION: Early initiation of medical thromboembolic prophylaxis appears safe in select patients with isolated SOI following blunt trauma. A prospective multicentre study is warranted. PMID- 26820319 TI - Surgeon unemployment: would practice sharing be a viable solution? AB - SUMMARY: Surgeon unemployment has become a crisis within Canadian surgery in recent years. Without dedicated governmental workforce planning, ensuring that new residency graduates can find employment will require new models of employment. Practice sharing, whereby a new graduate and a senior surgeon partner to divide their practices, allows the senior surgeon to wind down and the newer surgeon to ramp up. Importantly, this arrangement builds in formal mentoring, which is so important in the early years of starting a surgical practice. Practice sharing may be a solution for the workforce issues currently afflicting new surgical graduates across Canada. PMID- 26820320 TI - Trauma simulation in bilingual Canada: Insurmountable barrier or unexpected strength? Insights from the first bilingual S.T.A.R.T.T. course. AB - SUMMARY: The Standardized Trauma and Resuscitation Team Training (S.T.A.R.T.T.) course focuses on training multidisciplinary trauma teams: surgeons/physicians, registered nurses (RNs), respiratory therapists (RTs) and, most recently, prehospital personnel. The S.T.A.R.T.T. curriculum highlights crisis management (CRM) skills: communication, teamwork, leadership, situational awareness and resource utilization. This commentary outlines the modifications made to the course curriculum in order to satisfy the learning needs of a bilingual audience. The results suggest that bilingual multidisciplinary CRM courses are feasible, are associated with high participant satisfaction and have no clear detriments. PMID- 26820321 TI - Reversible and multi-cyclic protein-protein interaction in bacterial cellulosome mimic system using rod-shaped viral nanostructure. AB - The type II cohesin domain and type II dockerin of bacterial cellulosome were cloned from Clostridium thermocellum and expressed with the fusion of tobacco mosaic virus coat protein (TMVcp) and enhanced green fluorescent protein (EGFP), respectively, in Escherichia coli. The TMVcp-cohesin fusion protein was assembled to the stable and rod-shaped nanostructure (TMVcp-Coh rod) under a particular buffer condition, where many active cohesin proteins are biologically and densely displayed around the 3-dimensional surface of TMVcp-Coh rod. Using EGFP-dockerin as a fluorescent reporter, we confirmed that the Ca(2+)-dependent binding and dissociation between native cohesin and dockerin were reproduced with the two recombinant fusion proteins, TMVcp-cohesin and EGFP-dockerin. The multi-cyclic binding-dissociation operation of TMVcp-Coh rod and EGFP-dockerin was successfully performed with maintaining the reversible cohesin-dockerin interaction in every cycle. EGFP that was fused to dockerin as a proof-of-concept here can be switched to other functional proteins/peptides that need to be used in multi-cyclic operation. PMID- 26820322 TI - Constitutive production and efficient secretion of soluble full-length streptavidin by an Escherichia coli 'leaky mutant'. AB - Due to its various applications the protein streptavidin is a highly interesting target for heterologous production. This study focuses on different Escherichia coli-based constructs targeting a high-level expression and secretion of streptavidin to the medium. The effect of various promoters, variants of the target gene, leader sequences and host strains on expression and secretion into the culture broth was analyzed. Constitutive production of full-length streptavidin fused with the leader sequence of the bglA gene from Bacillus amyloliquefaciens by the periplasmic 'leaky mutant' E. coli JW1667-5 (Deltalpp 752:kan) at 30 degrees C generated the highest yield of the conditions tested, surpassing the extracellular concentration of a conventional T7-based expression system. Supplementation of the medium by the non-ionic surfactants Triton((r)) X 100 and X-45 led to an improved secretion of the protein to the culture supernatant. Tetrameric concentrations of streptavidin of 2790+/-166nM were reached in shake flasks at a productivity of 49.6nMh(-1). Optimization of conditions led to a successful transfer to the bioreactor, yielding a maximal concentration of 2608+/-169nM and a productivity of 65.2nMh(-1) in fed-batch operation. The proportion of biotin-blocked binding sites of 8.3+/-4.3% indicated a highly bioactive product. PMID- 26820324 TI - Autopsy. PMID- 26820325 TI - Bone and Soft Tissue Pathology. PMID- 26820323 TI - Early Detection of Pressure Ulcer Development Following Traumatic Spinal Cord Injury Using Inflammatory Mediators. AB - OBJECTIVE: To identify changes in concentrations of inflammatory mediators in plasma and urine after traumatic spinal cord injury (SCI) and before the occurrence of a first pressure ulcer. DESIGN: Retrospective; secondary analysis of existing data. SETTING: Acute hospitalization and inpatient rehabilitation sites at a university medical center. PARTICIPANTS: Individuals with a pressure ulcer and plasma samples (n=17) and individuals with a pressure ulcer and urine samples (n=15) were matched by age and plasma/urine sample days to individuals with SCI and no pressure ulcer (N=35). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Plasma and urine samples were assayed in patients with SCI, capturing samples within 4 days after the SCI to a week before the formation of the first pressure ulcer. The Wilcoxon signed-rank test was performed to identify changes in the inflammatory mediators between the 2 time points. RESULTS: An increase in concentration of the chemokine interferon-gamma-induced protein of 10kd/CXCL10 in plasma (P<.01) and a decrease in concentration of the cytokine interferon-alpha in urine (P=.01) were observed before occurrence of a first pressure ulcer (~4d) compared with matched controls. CONCLUSIONS: Altered levels of inflammatory mediators in plasma and urine may be associated with pressure ulcer development after traumatic SCI. These inflammatory mediators should be explored as possible biomarkers for identifying individuals at risk for pressure ulcer formation. PMID- 26820326 TI - Breast Pathology. PMID- 26820327 TI - Cardiovascular Pathology. PMID- 26820328 TI - Cytopathology. PMID- 26820330 TI - Education. PMID- 26820329 TI - Dermatopathology. PMID- 26820331 TI - Endocrine Pathology. PMID- 26820332 TI - Gastrointestinal Pathology. PMID- 26820333 TI - Genitourinary Pathology. PMID- 26820335 TI - Head and Neck Pathology. PMID- 26820334 TI - Gynecologic and Obstetric Pathology. PMID- 26820336 TI - Hematopathology. PMID- 26820338 TI - Informatics. PMID- 26820337 TI - Infectious Disease Pathology. PMID- 26820339 TI - Kidney/Renal Pathology. PMID- 26820340 TI - Liver. PMID- 26820341 TI - Neuropathology and Ophthalmic Pathology. PMID- 26820342 TI - Pancreas and Biliary Tree. PMID- 26820343 TI - Pathobiology. PMID- 26820345 TI - Pulmonary Pathology. PMID- 26820344 TI - Pediatric Pathology. PMID- 26820346 TI - Quality Assurance. PMID- 26820347 TI - Techniques. PMID- 26820350 TI - Adsorptive removal of Congo red from aqueous solutions using crosslinked chitosan and crosslinked chitosan immobilized bentonite. AB - Batch experiments were executed to investigate the removal of Congo red (CR) from aqueous solutions using the crosslinked chitosan (CCS) and crosslinked chitosan immobilized bentonite (CCS/BT composite). The CCS and CCS/BT composite were characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) techniques. The removal of CR was examined as a function of pH value of CR solution, contact time, and inorganic sodium salt and ionic strength. The equilibrium data of CCS and CCS/BT composite agreed well with the Langmuir model. The adsorption capacities of CCS and CCS/BT composite at 298K and natural pH value were 405 and 500 mg/g, respectively. The kinetic data correlated well with the pseudo-second-order model. The adsorption of CR onto the CCS was mainly controlled by chemisorption while the adsorption of CR onto the CCS/BT composite was controlled by chemisorption and the electrostatic attraction. PMID- 26820351 TI - Preparation of albumin based nanoparticles for delivery of fisetin and evaluation of its cytotoxic activity. AB - Fisetin is a well known flavonoid that shows several properties such as antioxidant, antiviral and anticancer activities. Its use in the pharmaceutical field is limited due to its poor aqueous solubility which results in poor bioavailability and poor permeability. The aim of our present study is to prepare fisetin loaded human serum albumin nanoparticles to improve its bioavailability. The nanoparticles were prepared by a desolvation method and characterized by spectroscopic and microscopic techniques. The particles were smooth and spherical in nature with an average size of 220 +/- 8 nm. The encapsulation efficiency was found to be 84%. The in vitro release profile showed a biphasic pattern and the release rate increases with increase in ionic strength of solution. We have also confirmed the antioxidant activity of the prepared nanoparticles by a DPPH (2,2 diphenyl-1-picrylhydrazyl) assay. Further its anticancer activity was evaluated using MCF-7 breast cancer cell lines. Our findings suggest that fisetin loaded HSA nanoparticles could be used to transfer fisetin to target areas under specific conditions and thus may find use as a delivery vehicle for the flavonoid. PMID- 26820352 TI - Protective effect of a polysaccharide from Rhizoma Atractylodis Macrocephalae on acute liver injury in mice. AB - A homogeneous polysaccharide was isolated and purified from Rhizoma Atractylodis Macrocephalae (RAM) and named PRAM2. Its average molecular weight was 19.6*10(3)Da and it was composed of rhamnose, xylose, arabinose, glucose, mannose and galactose in a ratio of 1: 1.3: 1.5: 1.8: 2.1: 3.2. In vitro experiments confirmed that PRAM2 presented an obvious effect to scavenge 1,1-diphenyl-2 picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) (DPPH), superoxide anion and hydroxyl radical. In vivo experiments confirmed that PRAM2 could reduce the liver weight, liver index, aspartate transaminase (AST) and alanine aminotransferase (ALT) activities in the serum; meanwhile, PRAM2 could significantly reduce nitric oxide synthase (NOS) activity, and nitric oxide (NO) and malonaldehyde (MDA) contents in the liver tissues, and increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. These results suggest that PRAM2 has a significant in vitro antioxidant activity and a protective effect on CCl4-induced liver injury in mice; the protective effect may be related to its anti-oxidation, its inhibition of NOS activity and NO level and its reduction of the production of free radicals. PMID- 26820353 TI - Evaluation of structural and functional properties of chitosan-chlorogenic acid complexes. AB - The objectives of the present study were to first synthesize chitosan-chlorogenic acid (CA) covalent complex and then compare structural and functional properties between chitosan-CA covalent complex and physical complex. First, chitosan-CA covalent complex was synthesized and its total phenolic content was as high as 276.5 +/- 6.2 mg/g. Then structural and functional properties of chitosan-CA covalent and physical complexes were analyzed. The covalent reaction induced formation of both amide and ester bonds in chitosan. Data of X-ray diffraction (XRD) and scanning electron microscopy (SEM) indicated that the complexations of CA changed crystallinity and morphology of chitosan, and covalent complexation induced a larger change of physical structure than physical complexation. In terms of functional properties, chitosan-CA covalent complex exhibited better thermal stability than physical complex in terms of antioxidant activity, and the viscosity of chitosan was significantly increased by covalent modification. PMID- 26820354 TI - Bioactive exopolysaccharides from a S. thermophilus strain: Screening, purification and characterization. AB - A lactic acid bacteria strain AR333 with high-production of exopolysaccharides (EPS) was screened out from 350 bacteria strains isolated from naturally fermented dairy products. It was identified as Streptococcus thermophilus by morphological observation, physiological and biochemical characteristics, and 16S rDNA sequence determination. The EPS from AR333 were purified through DEAE Sepharose Fast Flow and Sepharose CL-6B, and the purified fraction was designated as EPS333. In vitro test showed that EPS333 could stimulate macrophage RAW 264.7 to release NO significantly (p<0.05). The further work tried to elucidate the structural features of EPS333 via FT-IR spectrum, high-performance anion exchange chromatography (HPAEC) and high-performance size exclusion chromatography (HPSEC). The results showed that EPS333 was a pure neutral polysaccharide with monosaccharide composition of galactose and glucose in a molar ratio of 6:5. A certain amount of acetyl groups might exist in EPS333 according to the FT-IR spectrum. The molecular weight (Mw) was estimated to be 332 kDa. Current study suggested that the lactic bacteria strain AR333 could be a potential source of immunoregulatory polysaccharide. PMID- 26820355 TI - Optimizing the Management of Heart Failure With Preserved Ejection Fraction in the Elderly by Targeting Comorbidities (OPTIMIZE-HFPEF). AB - AIMS: The pathophysiology of heart failure with preserved ejection fraction (HFPEF) is not fully understood. A recently proposed mechanism for HFPEF is that it is a systemic pro-inflammatory state induced by comorbidities, leading to microvascular endothelial dysfunction and subsequent cardiac remodeling and dysfunction. We hypothesize that targeting comorbidities will improve outcomes in elderly patients with HFPEF. Thus, the aim of this study is to determine whether the combination of systematic screening and optimal management of prespecified comorbidities associated with HFPEF improves outcomes. METHODS: This multicenter, prospective, randomized intervention trial uses an open procedure with blinded endpoint assessment. Patients with HFPEF aged >60 years (n = 360) will be randomized 1:1 to the usual care or intervention arm of the trial. When randomized to the intervention arm, all patients will be systematically screened and optimally treated for the most frequent cardiovascular, metabolic, respiratory, and renal comorbidities. The primary endpoint is a composite clinical score that classifies each randomized patient as improved or deteriorated based on objective and subjective data at a 24-month follow-up performed by a blinded endpoint committee. CONCLUSION: Rather than targeting cardiac dysfunction, our study aims to present evidence for a possible paradigm shift in the management of HFPEF. Our novel concept focuses on the management of comorbidities as predisposing factors in HFPEF. PMID- 26820356 TI - Importance of the Birth Environment to Support Physiologic Birth. AB - The birth environment can support or hinder physiologic birth. Although most births occur in hospitals, there has been an increase in requests for home and birth center births. Nurses can support physiologic birth in different environments by ensuring a calm environment that helps reduce stress hormones known to slow labor. In any birth setting, nurses can encourage the use of facilities and equipment that support a physiologic labor and birth and aid the transition of the newborn. PMID- 26820357 TI - The Value of the Maternity Care Team in the Promotion of Physiologic Birth. AB - The benefits of normal, physiologic birth have been well documented. Health care providers such as nurses, midwives, and physicians have distinct and significant roles in the promotion of physiologic birth processes. By supporting women and families, doulas can enhance the maternity care team and further facilitate physiologic birth. A collaborative maternity care team can foster and support a common goal of safe, satisfying, and affordable care practices associated with physiologic birth. PMID- 26820358 TI - Combination of forward osmosis (FO) process with coagulation/flocculation (CF) for potential treatment of textile wastewater. AB - A novel combination of forward osmosis (FO) process with coagulation/flocculation (CF) (FO-CF) has been experimentally conceived for the treatment and reuse of textile wastewater. FO is employed to spontaneously recover water from the wastewater via osmosis and thus effectively reduces its volume with a dramatically enhanced dye concentration. CF is then applied to precipitate and remove dyes from the FO concentrated stream with much improved efficiency and reduced chemical dosage. The FO-CF hybrid system exhibits unique advantages of high water flux and recovery rate, well controlled membrane fouling, high efficiency, and minimal environmental impact. Using a lab-made thin-film composite (TFC) FO membrane, an initial water flux (Jw) of 36.0 L m(-2) h(-1) with a dye rejection of 99.9% has been demonstrated by using 2 M NaCl as the draw solution and synthetic textile wastewater containing multiple textile dyes, inorganic salts and organic additives as the feed under the FO mode. The Jw could be maintained at a high value of 12.0 L m(-2) h(-1) even when the recovery rate of the wastewater reaches 90%. Remarkable reverse fouling behavior has also been observed where the Jw of the fouled membrane can be almost fully restored to the initial value by physical flushing without using any chemicals. Due to the great dye concentration in the FO concentrated wastewater stream, the CF process could achieve more than 95% dye removal with a small dosage of coagulants and flocculants at 500-1000 ppm. The newly developed FO-CF hybrid process may open up new exploration of alternative technologies for the effective treatment and reuse of textile effluents. PMID- 26820359 TI - The Impact of Vein Mechanical Compliance on Arteriovenous Fistula Outcomes. AB - BACKGROUND: Arteriovenous fistulae (AVFs) are the preferred access for hemodialysis but suffer a high early failure rate. The aim of this study was to determine how venous distensibility, as measured in vitro, relates to early outcomes of AVF formed with the sampled vein. METHODS: Ethical approval was obtained for all aspects of this study. During AVF formation a circumferential segment of the target vein was sampled. Mechanical stress testing of the venous segments was undertaken using a dynamic mechanical analyzer, with progressive stress loading at 2 N/min to a maximum of 10 N or until sample disruption. Stress strain curves were obtained for vein samples and Young's modulus (YM) calculated. Duplex assessment of the fistulae was undertaken at 30 days. RESULTS: Thirty patients consented to participate with 29 samples obtained for analysis. Statistical comparison of YM demonstrated no relationship with common cardiovascular risk factors or dialysis status. Subject age greater than 65 was the only patient factor which showed a significant difference in YM (P = 0.05). Furthermore, a negative correlation was confirmed between age and YM (Pearson's r = -0.465, P < 0.05). Nine of the 29 subjects suffered an early AVF failure. Mann Whitney U testing for differences in distribution reported that YM was significantly higher in those fistulas which failed (P < 0.005). CONCLUSIONS: Reduced venous compliance appears to result in higher failure rates of AVFs. With the advancement of clinical tools such as speckle tracing ultrasound identification of vessel compliance in vivo may produce valuable additional information for clinicians planning AVF surgery. PMID- 26820360 TI - Ultrasensitive Nanoimmunosensor by coupling non-covalent functionalized graphene oxide platform and numerous ferritin labels on carbon nanotubes. AB - An ultrasensitive electrochemical nanostructured immunosensor for a breast cancer biomarker carbohydrate antigen 15-3 (CA 15-3) was fabricated using non-covalent functionalized graphene oxides (GO/Py-COOH) as sensor probe and multiwalled carbon nanotube (MWCNTs)-supported numerous ferritin as labels. The immunosensor was constructed by immobilizing a monoclonal anti-CA 15-3 antibody on the GO modified cysteamine (Cys) self-assembled monolayer (SAM) on an Au electrode (Au/Cys) through the amide bond formation between the carboxylic acid groups of GO/Py-COOH and amine groups of anti-CA 15-3. Secondary antibody conjugated MWCNT supported ferritin labels (Ab2-MWCNT-Ferritin) were prepared through the amide bond formation between amine groups of Ab2 and ferritin and carboxylic acid groups of MWCNTs. The detection of CA 15-3 was based on the enhanced bioelectrocatalytic reduction of hydrogen peroxide mediated by hydroquinone (HQ) at the GO/Py-COOH-based sensor probe. The GO/Py-COOH-based sensor probe and Ab2 MWCNT-Ferritin labels were characterized using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning electron microscope (SEM), transmission electron microscope (TEM), and x-ray photoelectron spectroscopy (XPS) techniques. Using differential pulse voltammetry (DPV) technique, CA 15-3 can be selectively detected as low as 0.01 +/- 0.07 U/mL in human serum samples. Additionally, the proposed CA 15-3 immunosensor showed excellent selectivity and better stability in human serum samples, which demonstrated that the proposed immunosensor has potentials in proteomic researches and diagnostics. PMID- 26820361 TI - MMP2-sensing up-conversion nanoparticle for fluorescence biosensing in head and neck cancer cells. AB - Upconversion nanoparticles (UCNPs) have extensive biological-applications because of their bio-compatibility, tunable optical properties and their ability to be excited by infrared radiation. Matrix metalloproteinases (MMPs) play important roles in extracellular matrix remodelling; they are usually found to significantly increase during cancer progression, and these increases may lead to poor patient survival. In this study, we produced a biosensor that can be recognized by MMP2 and then be unravelled by the attached quencher to emit visible light. We used 3.5-nm gold nanoparticles as a quencher that absorbed emission from UCNPs at a wavelength of 540 nm. The biosensor consists of an upconversion nanoparticle, MMP2-recognized polypeptides and quenchers. Here, UCNPs consisting of NaYF4:Yb(3+)/Er(3+) were prepared via a high temperature co precipitation method while protecting the oleic acid ligand. To improve the biocompatibility and modify the UCNPs with a polypeptide, they were coated with a silica shell and further conjugated with MMP-recognizing polypeptides. The polypeptide has two ends of featuring carboxylic and thiol groups that react with UCNPs and AuNPs, and the resulting nanoparticles were referred to as UCNP@p-Au. According to the in vitro cell viability analysis, UCNP@p-Au exhibited little toxicity and biocompatibility in head and neck cancer cells. Cellular uptake studies showed that the MMP-based biosensor was activated by 980-nm irradiation to emit green light. This MMP-based biosensor may serve as sensitive and specific molecular fluorescent probe in biological-applications. PMID- 26820362 TI - Mechanisms underlying atrial-selective block of sodium channels by Wenxin Keli: Experimental and theoretical analysis. AB - INTRODUCTION: Atrial-selective inhibition of cardiac sodium channel current (INa) and INa-dependent parameters has been shown to contribute to the safe and effective management of atrial fibrillation. The present study was designed to examine the basis for the atrial-selective actions of Wenxin Keli. METHODS: Whole cell INa was recorded at room temperature in canine atrial and ventricular myocytes. Trains of 40 pulses were elicited over a range of pulse durations and interpulse intervals to determine tonic and use-dependent block. A Markovian model for INa that incorporates interaction of Wenxin Keli with different states of the channel was developed to examine the basis for atrial selectivity of the drug. RESULTS: Our data indicate that Wenxin Keli does not bind significantly to either closed or open states of the sodium channel, but binds very rapidly to the inactivated state of the channel and dissociates rapidly from the closed state. Action potentials recorded from atrial and ventricular preparations in the presence of 5g/L Wenxin Keli were introduced into the computer model in current clamp mode to simulate the effects on maximum upstroke velocity (Vmax). The model predicted much greater inhibition of Vmax in atrial vs. ventricular cells at rapid stimulation rates. CONCLUSION: Our findings suggest that atrial selectivity of Wenxin Keli to block INa is due to more negative steady-state inactivation, less negative resting membrane potential, and shorter diastolic intervals in atrial vs. ventricular cells at rapid activation rates. These actions of Wenxin Keli account for its relatively safe and effective suppression of atrial fibrillation. PMID- 26820364 TI - Prognostic impact of spontaneous coronary artery dissection in young female patients with acute myocardial infarction: A report from the Angina Pectoris Myocardial Infarction Multicenter Investigators in Japan. AB - BACKGROUND: We sought to compare the prognosis of patients with spontaneous coronary artery dissection (SCAD) and atherosclerosis as the cause of acute myocardial infarction (AMI), especially in young females. METHODS AND RESULTS: A total of 20,195 patients with AMI at 20 institutions between 2000 and 2013 were retrospectively studied. Major adverse cardiac event (MACE: cardiac death, AMI or urgent revascularization) was the endpoint. The overall prevalence of SCAD was 0.31% (n=63; female, 94%). SCAD developed following emotional stress in 29% of patients. Revascularization was performed in 56% (35 of 63 patients), and SCAD recurrence developed in the originally involved vessel in 6 of 35 patients with revascularization, compared to none among 28 patients after conservative therapy (p=0.002). We compared the clinical characteristics of young female AMI patients aged <=50years in the SCAD (n=45) and no-SCAD groups (atherosclerotic AMI, n=55). During a median follow-up of 50months, SCAD recurred in 27% of patients, of which 42% was in the first 30days. Kaplan-Meier analysis showed a significantly higher incidence of MACE in the SCAD group compared to the no-SCAD group (hazard ratio, 6.91; 95% confidence interval, 2.5 to 24.3; p<0.001), although the rate of successful percutaneous coronary intervention for SCAD was as high as 92%. CONCLUSIONS: Young female patients with SCAD represent a high-risk subgroup of patients with AMI and require close follow-up. PMID- 26820363 TI - Impact of chronic kidney disease on left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation. AB - BACKGROUND: Left atrial appendage occlusion (LAAO) using the Amplatzer cardiac plug (ACP) is a preventive treatment of atrial fibrillation related thromboembolism. AIM: To assess the safety and efficacy of LAAO in patients with chronic kidney disease (CKD). METHODS: Among the ACP multicentre registry, 1014 patients (75+/-8yrs) with available renal function were included. RESULTS: Patients with CKD (N=375, CHA2DS2-VASc: 4.9+/-1.5, HASBLED: 3.4+/-1.3) were at higher risk than patients without CKD (N=639, CHA2DS2-VASc: 4.2+/-1.6, HASBLED: 2.9+/-1.2; p<0.001 for both). Procedural (97%) and occlusion (99%) success were similarly high in all stages of CKD. Peri-procedural major adverse events (MAE) were observed in 5.1% of patients, 0.8% of death, with no difference between patients with and those without CKD (6.1 vs 4.5%, p=0.47). In patients with complete follow-up (1319 patients years), the annual stroke+transient ischaemic attack (TIA) rate was 2.3% and the observed bleeding rate was 2.1% (62 and 60% less than expected, similarly among patients with and those without CKD). Kaplan Meier analysis showed a lower overall survival (84 vs 96% and 84 vs 93% at 1 and 2yrs. respectively; p<0.001) among patients with an eGFR <30ml/min/1.73m(2). CONCLUSION: LAAO using the ACP has a similar procedural safety among CKD patients compared to patients with normal renal function. LAAO with ACP offers a dramatic reduction of stroke+TIA rate and of bleeding rate persistent in all stages of CKD, as compared to the expected annual risk. PMID- 26820366 TI - RKIP corrects impaired beta (2)-adrenergic receptor vasodilatation in hypertension by downregulation of GRK2. PMID- 26820365 TI - Targeted resequencing identifies TRPM4 as a major gene predisposing to progressive familial heart block type I. AB - BACKGROUND: Progressive cardiac conduction disease (PCCD) is one of the most common cardiac conduction disturbances. It has been causally related to rare mutations in several genes including SCN5A, SCN1B, TRPM4, LMNA and GJA5. METHODS AND RESULTS: In this study, by applying targeted next-generation sequencing (NGS) in 95 unrelated patients with PCCD, we have identified 13 rare variants in the TRPM4 gene, two of which are currently absent from public databases. This gene encodes a cardiac calcium-activated cationic channel which precise role and importance in cardiac conduction and disease is still debated. One novel variant, TRPM4-p.I376T, is carried by the proband of a large French 4-generation pedigree. Systematic familial screening showed that a total of 13 family members carry the mutation, including 10 out of the 11 tested affected individuals versus only 1 out of the 21 unaffected ones. Functional and biochemical analyses were performed using HEK293 cells, in whole-cell patch-clamp configuration and Western blotting. TRPM4-p.I376T results in an increased current density concomitant to an augmented TRPM4 channel expression at the cell surface. CONCLUSIONS: This study is the first extensive NGS-based screening of TRPM4 coding variants in patients with PCCD. It reports the third largest pedigree diagnosed with isolated Progressive Familial Heart Block type I and confirms that this subtype of PCCD is caused by mutation-induced gain-of-expression and function of the TRPM4 ion channel. PMID- 26820367 TI - Is sEHi lowering LDL-C by reducing expression of PCSK9 through SREBP2 pathway? PMID- 26820368 TI - Chronic thromboembolic pulmonary hypertension and schizophrenia. PMID- 26820369 TI - Iron deficiency and functional capacity in patients with advanced heart failure with preserved ejection fraction. PMID- 26820370 TI - The association between circulating anti-angiogenic isoform of vascular endothelial growth factor and clinical profiles in patients with peripheral artery disease. PMID- 26820371 TI - Patent foramen ovale and paradoxical thromboembolism. Which treatment is the most appropriate? PMID- 26820372 TI - Extremely severe aortic stenosis developed in a young female patient with underdiagnosis of homozygous familial hypercholesterolemia: An 8-year follow-up. PMID- 26820373 TI - The risk of thromboembolism in patients with schizophrenia. PMID- 26820374 TI - Frontal transcranial direct current stimulation (tDCS) abolishes list-method directed forgetting. AB - It is a point of controversy as to whether directed forgetting effects are a result of active inhibition or a change of context initiated by the instruction to forget. In this study we test the causal role of active inhibition in directed forgetting. By applying cathodal transcranial direct current stimulation (tDCS) over the right prefrontal cortex we suppressed cortical activity commonly associated with inhibitory control. Participants who underwent real brain stimulation before completing the directed forgetting paradigm showed no directed forgetting effects. Conversely, those who underwent sham brain stimulation demonstrated classical directed forgetting effects. We argue that these findings suggest that inhibition is the primary mechanism that results in directed forgetting costs and benefits. PMID- 26820375 TI - Dopamine improves exploration after expectancy violations and induces psychotic like experiences in patients with Parkinson's disease. AB - Dopamine neurons are sensitive to novel and rewarding events, and dopamine signals can modulate learning in higher-level brain networks. Additionally, dopamine abnormalities appear to be central to the pathophysiology of schizophrenia spectrum disorders. In this study, we investigate the dopaminergic modulation of schizotypal traits and exploration after expectancy violations in Parkinson's disease (PD) patients on dopamine replacement therapy. Exploration after expectancy violations was measured with a latent inhibition and an anomaly categorisation task. Patients with PD had significantly elevated levels of schizotypy and reduced latent inhibition, relative to the controls. Anomaly categorisation was enhanced at trend level among the patients. Dopaminergic antiparkinsonian drugs showed dose-dependent effects: they induced psychotic-like experiences, and at the same time, they disrupted latent inhibition and made categorisation of anomaly more efficient. Most of these findings were replicated in an independent sample of patients with PD. An up-regulated dopamine system in medicated PD patients might tune higher-level brain networks to engage in learning when faced with unexpected information, and therefore hasten the updating of internal models. PMID- 26820376 TI - Microglial polarization dynamics in dorsal spinal cord in the early stages following chronic sciatic nerve damage. AB - Peripheral nerve injury can lead to activation of spinal microglia, which can mediate neuroinflammation and contribute to neuropathic pain following nerve injury. Activated microglia may manifest with either pro-inflammatory M1 phenotype or anti-inflammatory M2 phenotype, which may lead to detrimental or beneficial roles in the nervous system. In this study, microglia numbers, morphology and gene profiles were examined in the dorsal spinal cord of rats over 14 days following sciatic nerve chronic constriction injury (CCI). The morphology of some microglia changed from a surveying to an activated state within 1 day of CCI. Neuropathic pain developed within seven to 14 days following injury and microglia numbers were increased, with almost all in the dorsal spinal cord morphologically defined as activated. At day one after CCI, both M1 and M2 microglia-related genes were increased but only M1 microglia-related genes remained elevated at day seven and 14 thereafter. These results indicate that both M1 and M2 microglia were activated in the dorsal spinal cord one day after CCI but the microglia skewed towards M1 phenotype during the following seven and 14 days. PMID- 26820379 TI - Dynamic Symmetry Breaking Hidden in Fano Resonance of a Molecule: S1 State of Diazirine Using Quantum Wave Packet Propagation. AB - Fano resonance in the predissociation of the S1 state of diazirine was studied by applying a time-dependent wave packet propagation method, and dynamic symmetry breaking (DSB) around the stationary structure of S1 was disclosed in a detailed analysis of this theoretical result. The DSB was found to originate in coupling between the asymmetric C-N2 stretching and CH2 wagging modes, suggesting that there is a slight time gap between ring opening and the concurrent dragging of two H atoms of the CH2 moiety. Although the depth of the double well due to DSB is just 0.011 eV, its presence noticeably affects the early time dynamics and observed spectrum. PMID- 26820378 TI - Fabrication of Nanometer- and Micrometer-Scale Protein Structures by Site Specific Immobilization of Histidine-Tagged Proteins to Aminosiloxane Films with Photoremovable Protein-Resistant Protecting Groups. AB - The site-specific immobilization of histidine-tagged proteins to patterns formed by far-field and near-field exposure of films of aminosilanes with protein resistant photolabile protecting groups is demonstrated. After deprotection of the aminosilane, either through a mask or using a scanning near-field optical microscope, the amine terminal groups are derivatized first with glutaraldehyde and then with N-(5-amino-1-carboxypentyl)iminodiacetic acid to yield a nitrilo triacetic-acid-terminated surface. After complexation with Ni(2+), this surface binds histidine-tagged GFP and CpcA-PEB in a site-specific fashion. The chemistry is simple and reliable and leads to extensive surface functionalization. Bright fluorescence is observed in fluorescence microscopy images of micrometer- and nanometer-scale patterns. X-ray photoelectron spectroscopy is used to study quantitatively the efficiency of photodeprotection and the reactivity of the modified surfaces. The efficiency of the protein binding process is investigated quantitatively by ellipsometry and by fluorescence microscopy. We find that regions of the surface not exposed to UV light bind negligible amounts of His tagged proteins, indicating that the oligo(ethylene glycol) adduct on the nitrophenyl protecting group confers excellent protein resistance; in contrast, exposed regions bind His-GFP very effectively, yielding strong fluorescence that is almost completely removed on treatment of the surface with imidazole, confirming a degree of site-specific binding in excess of 90%. This simple strategy offers a versatile generic route to the spatially selective site specific immobilization of proteins at surfaces. PMID- 26820380 TI - Intraband Luminescence from HgSe/CdS Core/Shell Quantum Dots. AB - HgSe/CdS core/shell CQD are synthesized, and the changes in the optical absorption and luminescence are investigated. While HgSe quantum dots are naturally n-doped after synthesis, both as colloidal solutions and as films, the HgSe/CdS core/shell dots in solution lose the n-doping, as seen from the optical absorption in solution. However, n-doping is regained in films, and the intraband luminescence of the films of HgSe/CdS is greater than that of the cores. The shell also vastly improves the stability of the quantum dots films against sintering at 200 degrees C. After annealing at that temperature, the HgSe/CdS films retain a narrow intraband emission and sustain a higher laser power leading to brighter emission at 5 MUm. PMID- 26820381 TI - Quercetin-3-O-glucoside suppresses pancreatic cancer cell migration induced by tumor-deteriorated growth factors in vitro. AB - Analysis using Universal exPress Codes (UPCs) with the public microarray database GEO indicates significantly higher mRNA expressions of VEGF-A, bFGF, and bFGFR2 in pancreatic cancers than those in normal pancreatic tissues. Human pancreatic cancer cell line CFPAC-1 and SNU-213 had relatively differential sensitivity to exogenous VEGF-A, bFGF, and TGF-beta1 in migration property. Treatment of quercetin-3-O-glucoside suppressed the migratory activity induced by TGF-beta and VEGF-A even at relatively low dosages in CFPAC-1, but not in bFGF-activated SNU 213 cells. However, high dosages of quercetin-3-O-glucoside sufficiently suppressed the migratory activity induced by bFGF in SNU-213 cells. Furthermore, co-treatment with low dose of gemcitabine plus quercetin-3-O-glucoside showed synergistic inhibition effects on the infiltrate activity induced by bFGF in CFPAC-1 and SNU-213 cells. These results collectively suggested that quercetin-3 O glucoside could act as an inhibitor of local metastasis induced by various growth factors in pancreatic cancers and be an effective adjuvant to boost chemotherapeutic efficacy of gemcitabine, currently used in pancreatic cancers. PMID- 26820383 TI - Type of Atrial Fibrillation and Clinical Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement. AB - BACKGROUND: There are limited data available regarding the relationship between atrial fibrillation (AF) clinical type, oral anticoagulation (OAC) treatment, and clinical outcome after transcatheter aortic valve replacement (TAVR). The study was designed to evaluate this relationship. METHODS: We analyzed data from the Rabin Medical Center TAVR registry, including 319 consecutive patients who underwent TAVR from 2008 to 2014. Patients were divided into three groups based on their history of AF: sinus rhythm (SR), paroxysmal AF (PAF), or nonparoxysmal AF (NPAF). RESULTS: There were 211 (66%), 56 (18%), and 52 (16%) patients in the SR, PAF, and NPAF groups, respectively. The cumulative risk for stroke or death at 2 years was highest among patients with NPAF (38%), but similarly low in PAF (15%) and SR patients (16%, P < 0.001). By multivariate analysis, patients with NPAF demonstrated a significantly higher risk of stroke or death (HR = 2.76, 95% CI 1.63-4.66, P < 0.001), as compared with SR. In contrast, patients with PAF had a similar risk of stroke or death compared with SR (HR = 0.80, P = 0.508). Patients with NPAF not treated with OAC demonstrated an 8.3-fold (P < 0.001) increased risk of stroke or death, whereas patients with PAF not treated with OAC had a similar risk of stroke or death compared with the SR group (HR = 1.25, P = 0.569). CONCLUSION: History of NPAF, but not PAF, is associated with a significant increased risk of stroke or death compared with sinus rhythm in patients undergoing TAVR. PMID- 26820382 TI - TGF-beta1 improves mucosal IgA dysfunction and dysbiosis following intestinal ischaemia-reperfusion in mice. AB - Intestinal ischaemia/reperfusion (I/R) severely disrupts gut barriers and leads to high mortality in the critical care setting. Transforming growth factor (TGF) beta1 plays a pivotal role in intestinal cellular and immune regulation. However, the effects of TGF-beta1 on intestinal I/R injury remain unclear. Thus, we aimed to investigate the effects of TGF-beta1 on gut barriers after intestinal I/R and the molecular mechanisms. Intestinal I/R model was produced in mice by clamping the superior mesenteric artery for 1 hr followed by reperfusion. Recombinant TGF beta1 was intravenously infused at 15 min. before ischaemia. The results showed that within 2 hrs after reperfusion, intestinal I/R disturbed intestinal immunoglobulin A class switch recombination (IgA CSR), the key process of mucosal IgA synthesis, and resulted in IgA dysfunction, as evidenced by decreased production and bacteria-binding capacity of IgA. Meanwhile, the disruptions of intestinal microflora and mucosal structure were exhibited. Transforming growth factor-beta1 activated IgA CSR as evidenced by the increased activation molecules and IgA precursors. Strikingly, TGF-beta1 improved intestinal mucosal IgA dysfunction, dysbiosis and epithelial damage at the early stage after reperfusion. In addition, SB-431542, a specific inhibitor of activating mothers against decapentaplegic homologue (SMAD) 2/3, totally blocked the inductive effect of TGF-beta1 on IgA CSR and almost abrogated the above protective effects on intestinal barriers. Taken together, our study demonstrates that TGF-beta1 protects intestinal mucosal IgA immunity, microbiota and epithelial integrity against I/R injury mainly through TGF-beta receptor 1/SMAD 2/3 pathway. Induction of IgA CSR may be involved in the protection conferred by TGF-beta1. PMID- 26820384 TI - Structure of OxyA tei: completing our picture of the glycopeptide antibiotic producing Cytochrome P450 cascade. AB - Cyclization of glycopeptide antibiotic precursors occurs in either three or four steps catalyzed by Cytochrome P450 enzymes. Three of these enzymes have been structurally characterized to date with the second enzyme along the pathway, OxyA, escaping structural analysis. We are now able to present the structure of OxyAtei involved in teicoplanin biosynthesis - the same enzyme recently shown to be the first active OxyA homolog. In spite of the hydrophobic character of the teicoplanin precursor, the polar active site of OxyAtei and its affinity for certain azole inhibitors hint at its preference for substrates with polar decorations. PMID- 26820385 TI - Home nursing care with the self-care model improves self-efficacy of patients with chronic obstructive pulmonary disease. AB - AIM: This study was carried out as an intervention study to determine the effect of nursing care provided at home with the self-care model on the self-efficacy of patients with chronic obstructive pulmonary disease in northern Turkey. METHODS: The study sample totaled 106 patients with chronic obstructive pulmonary disease divided into two groups. The intervention group and the control group each included 53 patients. To collect data, the patient data sheet, Orem's self-care model-based data collection form, symptom evaluation form, Medical Research Council dyspnea scale, and the chronic obstructive pulmonary disease self efficacy scale (CSES) were used. The nursing care applied for the intervention group consisted of four visits, two during the first month and two for the next 2 months. An educational guidebook was distributed to the intervention group during the first visit, and at all visits, education, care, and supervision were provided according to the care plan. All data were analyzed with the number, percentage, chi(2) -test, Kruskal-Wallis H test, Wilcoxon rank sum test, and Mann Whitney U-test. RESULTS: The dyspnea level measured at the last visit for the control group was high compared with the intervention group (P < 0.05). The chronic obstructive pulmonary disease self-efficacy scale scores for subscale dimensions at the last visit and the general score for the intervention group were high compared with the first visit scores (P < 0.05). CONCLUSION: According to the study results, home nursing care based on the Orem's self-care model is effective in improving self-efficacy of patients with chronic obstructive pulmonary disease. PMID- 26820386 TI - Rh2(II,III) Catalysts with Chelating Carboxylate and Carboxamidate Supports: Electronic Structure and Nitrene Transfer Reactivity. AB - Dirhodium-catalyzed C-H amination is hypothesized to proceed via Rh2-nitrene intermediates in either the Rh2(II,II) or Rh2(II,III) redox state. Herein, we report joint theoretical and experimental studies of the ground electronic state (GES), redox potentials, and C-H amination of [Rh2(II,III)(O2CCH3)4(L)n](+) (1_L) (L = none, Cl(-), and H2O), [Rh2(esp)2](+) (2), and Rh2(espn)2Cl (3) (esp = alpha,alpha,alpha',alpha'-tetramethyl-1,3-benzenedipropanoate and espn = alpha,alpha,alpha',alpha'-tetramethyl-1,3-benzenedipropanamidate). CASSCF calculations on 1_L yield a wave function with two closely weighted configurations, (delta*)(2)(pi1*)(2)(pi2*)(1) and (delta*)(2)(pi1*)(1)(pi2*)(2), consistent with reported EPR g values [Chem. Phys. Lett. 1986, 130, 20-23]. In contrast, EPR spectra of 2 show g values consistent with the DFT-computed (pi*)(4)(delta*)(1) GES. EPR spectra and Cl K-edge XAS for 3 are consistent with a (pi*)(4)(delta*)(1) GES, as supported by DFT. Nitrene intermediates 2N_L and 3N_L are also examined by DFT (the nitrene is an NSO3R species). DFT calculations suggest a doublet GES for 2N_L and a quartet GES for 3N_L. CASSCF calculations describe the GES of 2N as Rh2(II,II) with a coordinated nitrene radical cation, (pi*)(4)(delta*)(2)(pi(nitrene,1))(1)(pi(nitrene,2))(0). Conversely, the GES of 3N is Rh2(II,III) with a coordinated triplet nitrene, (pi*)(4)(delta*)(1)(pi(nitrene,1))(1)(pi(nitrene,2))(1). Quartet transition states ((4)TSs) are found to react via a stepwise radical mechanism, whereas (2)TSs are found to react via a concerted mechanism that is lower in energy compared to (4)TSs for both 2N_L and 3N_L. The experimental (determined by intramolecular competition) and (2)TS-calculated kinetic isotopic effect (KIE) shows a KIE ~ 3 for both 2N and 3N, which is consistent with a concerted mechanism. PMID- 26820387 TI - Interim Guidelines for the Evaluation and Testing of Infants with Possible Congenital Zika Virus Infection - United States, 2016. AB - CDC has developed interim guidelines for health care providers in the United States who are caring for infants born to mothers who traveled to or resided in an area with Zika virus transmission during pregnancy. These guidelines include recommendations for the testing and management of these infants. Guidance is subject to change as more information becomes available; the latest information, including answers to commonly asked questions, can be found online (http://www.cdc.gov/zika). Pediatric health care providers should work closely with obstetric providers to identify infants whose mothers were potentially infected with Zika virus during pregnancy (based on travel to or residence in an area with Zika virus transmission [http://wwwnc.cdc.gov/travel/notices]), and review fetal ultrasounds and maternal testing for Zika virus infection (see Interim Guidelines for Pregnant Women During a Zika Virus Outbreak*) (1). Zika virus testing is recommended for 1) infants with microcephaly or intracranial calcifications born to women who traveled to or resided in an area with Zika virus transmission while pregnant; or 2) infants born to mothers with positive or inconclusive test results for Zika virus infection. For infants with laboratory evidence of a possible congenital Zika virus infection, additional clinical evaluation and follow-up is recommended. Health care providers should contact their state or territorial health department to facilitate testing. As an arboviral disease, Zika virus disease is a nationally notifiable condition. PMID- 26820388 TI - Versatile Route to Arylated Fluoroalkyl Bromide Building Blocks. AB - New difunctionalized and fluoroalkylated silyl reagents have been prepared that react with silver and copper salts to afford active catalysts that can be used to synthesize arylated fluoroalkyl bromide building blocks. It has been shown that the [(phen)Ag(CF2)nBr] intermediates are capable of transferring both the phenanthroline ligand and the fluoroalkyl bromide chain to copper iodide, eliminating the need for a preligated copper salt precursor. The methodology is compatible with various chain lengths of the fluoroalkyl halide functionality. PMID- 26820389 TI - Cardiometabolic risk factors in native populations living at high altitudes. AB - BACKGROUND: It is generally accepted that metabolic changes that take place in individuals exposed to high elevation are because of ambient hypoxia, which occurs as a consequence of a low total atmospheric pressure. The discovery of hypoxia inducible factor 1 (HIF1), a transcription factor, has been a breakthrough in the understanding of adaption to high altitudes. OBJECTIVE: The purpose of the present review was to discuss specific epidemiological aspects of cardiovascular disease (CVD) risk factors and their mechanisms in vulnerable, understudied populations living at high altitudes. RESULTS: Obesity prevalence has been inversely associated with elevation. HIF1 has been related to plasma leptin--a hormone secreted by adipose tissue that produces negative feedback on appetite--and inversely associated with obesity. Diverse factors, such as genetics, chronic hypoxia, diet and lifestyle behaviours, could have an influence on the high dyslipidaemia rates of high-altitude natives. Hypoxia could mediate the effects of altitude on human physiology, including lipid metabolism. Genetic studies suggest that dyslipidaemia could be related to the HIF1. Hypoxia inhibits oxidative phosphorylation and stimulates the oxygen signalling pathway through the HIF1. Low fasting glycaemia in individuals at high altitudes has been shown. An increased GLUT4 protein content in skeletal muscle in response to hypoxia has been reported and could be associated with lower glucose levels. Given the high prevalence of dyslipidaemia and the low prevalence of obesity and diabetes in these impoverished high-altitude communities, changes in lifestyle including decreased physical activity and the consumption of a more westernised diet would likely increase the prevalence of CVD related mortality. CONCLUSIONS: Control over major CVD risk factors, when identified early, could be the key to reducing morbidity and mortality in patients with limited access to medical services such as Native populations. PMID- 26820390 TI - Selective Antimicrobial Activities and Action Mechanism of Micelles Self Assembled by Cationic Oligomeric Surfactants. AB - This work reports that cationic micelles formed by cationic trimeric, tetrameric, and hexameric surfactants bearing amide moieties in spacers can efficiently kill Gram-negative E. coli with a very low minimum inhibitory concentration (1.70-0.93 MUM), and do not cause obvious toxicity to mammalian cells at the concentrations used. With the increase of the oligomerization degree, the antibacterial activity of the oligomeric surfactants increases, i.e., hexameric surfactant > tetrameric surfactant > trimeric surfactant. Isothermal titration microcalorimetry, scanning electron microscopy, and zeta potential results reveal that the cationic micelles interact with the cell membrane of E. coli through two processes. First, the integrity of outer membrane of E. coli is disrupted by the electrostatic interaction of the cationic ammonium groups of the surfactants with anionic groups of E. coli, resulting in loss of the barrier function of the outer membrane. The inner membrane then is disintegrated by the hydrophobic interaction of the surfactant hydrocarbon chains with the hydrophobic domains of the inner membrane, leading to the cytoplast leakage. The formation of micelles of these cationic oligomeric surfactants at very low concentration enables more efficient interaction with bacterial cell membrane, which endows the oligomeric surfactants with high antibacterial activity. PMID- 26820391 TI - Novel, isoform-selective, cholecystokinin A receptor antagonist inhibits colon and pancreatic cancers in preclinical models through novel mechanism of action. AB - Colon and pancreatic cancers contribute to 90,000 deaths each year in the USA. These cancers lack targeted therapeutics due to heterogeneity of the disease and multiple causative factors. One important factor that contributes to increased colon and pancreatic cancer risk is gastrin. Gastrin mediates its actions through two G-protein coupled receptors (GPCRs): cholecystokinin receptor A (CCK-A) and CCK-B/gastrin receptor. Previous studies have indicated that colon cancer predominantly expresses CCK-A and responds to CCK-A isoform antagonists. However, many CCK-A antagonists have failed in the clinic due to poor pharmacokinetic properties or lack of efficacy. In the present study, we synthesized a library of CCK-A isoform-selective antagonists and tested them in various colon and pancreatic cancer preclinical models. The lead CCK-A isoform, selective antagonist PNB-028, bound to CCK-A at 12 nM with a 60-fold selectivity towards CCK-A over CCK-B. Furthermore, it inhibited the proliferation of CCK-A-expressing colon and pancreatic cancer cells without affecting the proliferation of non cancerous cells. PNB-028 was also extremely effective in inhibiting the growth of MAC-16 and LoVo colon cancer and MIA PaCa pancreatic cancer xenografts in immune compromised mice. Genome-wide microarray and kinase-array studies indicate that PNB-028 inhibited oncogenic kinases and angiogenic factors to inhibit the growth of colon cancer xenografts. Safety pharmacology and toxicology studies have indicated that PNB-028 is extremely safe and has a wide safety margin. These studies suggest that targeting CCK-A selectively renders promise to treat colon and pancreatic cancers and that PNB-028 could become the next-generation treatment option. PMID- 26820393 TI - Benign Cardiac Effects of Hemoglobin H Disease. AB - BACKGROUND/AIMS: Hemoglobin H (HbH) disease is associated with iron overload, but whether this results in serious cardiac or vascular sequelae is unresolved. METHODS: We identified 39 adult subjects (age 42 +/- 12 years, 13 men) with HbH disease who had undergone echocardiography, 27 of whom had also undergone cardiac and liver magnetic resonance assessment of iron loading using T2*-weighted imaging. RESULTS: None of the subjects had a history of heart failure or arrhythmias. There were 13/39 subjects with a ferritin level within the sex-based normal range and only 4/39 had ferritin >1,000 ng/ml. Left ventricular (LV) and left atrial dilatation was common, but LV ejection fraction was normal (>=55%) in all subjects. Age was positively correlated with log ferritin in the 27 nontransfused subjects (r = 0.43) and was inversely correlated with the transmitral E wave and E/A ratio (r = -0.69 and r = -0.79, respectively), but no relation of log ferritin with E or E/A was evident. The peak tricuspid regurgitation velocity was normal in 24/29 subjects for whom this was obtained, and it was no more than mildly elevated in the other 5. None of the tested subjects had an abnormal cardiac T2* reading, but half had evidence of liver iron loading. CONCLUSION: No myocardial iron loading or serious cardiac or vascular sequelae were identified in this cohort with HbH disease. PMID- 26820392 TI - The IL-24 gene protects human umbilical vein endothelial cells against H2O2 induced injury and may be useful as a treatment for cardiovascular disease. AB - The aim of the present study was to investigate the protective effects of interleukin-24 (IL-24) on hydrogen peroxide (H2O2)-induced vascular endothelial injury and to examine the association between IL-24 and cardiovascular disease. Human umbilical vein endothelial cells (HUVECs) were exposed to increasing concentrations of H2O2 in the presence or absence of IL-24, which was introduced via Lipofectamine(r) 2000-mediated transfection. The successful uptake of the IL 24 plasmid was confirmed by RT-PCR at 24 h post-transfection. The effects of H2O2 and IL-24 on the proliferation and migration of the HUVECs was determined using cell migration assays. Cell viability was determined using a Cell Counting Kit-8 (CCK-8). Apoptosis and the measurement of the intracellular reactive oxygen species (ROS) levels were determined by flow cytometry, and the levels of caspase 3, which is associated with apoptosis, were determined by western blot analysis. Real-time PCR and western blot analysis were also used to measure the levels of multiple cardiovascular disease-associated factors. In vivo experiments were also performed using a rat model of hypertension which was constructed by angiotensin II infusion using an osmotic pump. The mRNA and protein levels of IL-24 were measured in both the control and hypertensive rats; the effects of treatment with enalapril and nifedipine on the IL-24 levels were also examined. Our results revealed that IL-24 protected against the H2O2-mediated abnormal increase in HUVEC proliferation. IL-24 also antagonized H2O2 by reducing the content of ROS in the cells, thus decreasing cellular oxidative damage, improving the cellular survival rate, reducing apoptosis and decreasing the expression of cardiovascular disease-related factors. The results from our in vivo animal experiments revealed that IL-24 expression was lower in the hypertensive rats compared to the healthy controls. Additionally, the IL-24 levels increased following anti-hypertensive therapy. The findings of our study indicate that IL-24 protects against H2O2 mediated endothelial cell damage and may thus provide a novel therapeutic strategy for treatment of cardiovascular disease. PMID- 26820394 TI - Differential microRNA expression profiling of mesothelioma and expression analysis of miR-1 and miR-214 in mesothelioma. AB - Malignant mesothelioma is a highly aggressive cancer with poor prognosis and refractory to currently available therapies. Most of the patients with advanced invasive nature are not amenable to surgical resection and/or available anticancer therapy, thus development of novel effective therapeutic regimes is needed. Aberrant expression of microRNAs (miRNAs) has been proposed to contribute to carcinogenesis and aggressiveness of mesothelioma. We analyzed miRNA expression in mesothelioma cell lines using TaqMan miRNA expression array and found significant number of miRNAs, which showed increased or lost expression. We validated the increased expression of miR-182, and miR-183 in mesothelioma cell lines by individual miRNA assays and SmartFlare miRNA probes. We further investigated the miR-1, and miR-214, which were not expressed in mesothelioma cells by real-time RT-PCR. Transfection of mesothelioma cells, ACC-Meso-1 and CRL5915, with miRNA mimic (hsa-miR-1 mimic and hsa-miR-214 mimic) led to inhibition of cell growth, invasion and migration. We paid attention to PIM1, the target gene of both miR-1 and miR-214 miRNAs and which was found overexpressed in mesothelioma cells, and miR-1 and miR-214 mimic transfection of mesothelioma cell lines showed downregulation of PIM1 by western blot analysis. The miRNAs, miR-1 and miR-214, may play a role in carcinogenesis of mesothelioma thus might be considered as candidate therapeutic targets in mesothelioma. PMID- 26820395 TI - Antioxidant Activity of Heracleum persicum Fruit Extract: Evidence from a Randomized Controlled Trial. AB - Oxidative stress is a unifying feature of several cardiometabolic risk factors, and has been suggested to be implicated in atherogenesis. This study aimed to investigate the efficacy of supplementation with Heracleum persicum fruit-a common dietary spice-in modulating systemic biomarkers of oxidative stress in subjects undergoing coronary angiography. Twenty-seven subjects with minimal coronary artery disease (CAD; defined as < 50% obstruction in the coronary arteries) were selected for this trial and were randomly allocated to Heracleum persicum hydroalcoholic fruit extract (n = 15; 300 mg/day) or placebo (n = 12) for a period of six months. Patients were visited monthly and asked to report the adverse events during the treatment period. Serum levels of malondialdehyde (MDA), reduced glutathione (GSH) and total antioxidant capacity (TAC), and enzymatic activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were determined at baseline and at the end of trial. Comparison of changes in the evaluated biomarkers of oxidative stress indicated a significantly greater effect of H. persicum extract versus placebo in reducing serum MDA (p = .001), and elevating GSH (p = .001), and TAC (p = .001) concentrations, as well as activities of GPx (p = .001) and CAT (p = .001). The groups were comparable with respect to changes in serum SOD activities during the course of trial (p = .255). The findings of the present randomized double-blind placebo-controlled trial clearly support the efficacy of H. persicum fruit extract as a safe antioxidant supplement in subjects with minimal CAD. PMID- 26820396 TI - Molly users versus nonusers in a sample of college alcohol drinkers: Differences in substance-related harms and sensation seeking. AB - BACKGROUND: Molly is one form of MDMA (3,4-methylenedioxymethamphetamine) that is touted to be more "pure" and potentially less harmful than other forms, such as ecstasy. Media reports and case studies suggest that this drug is popular among college students and is related to adverse health problems. The current study sought to address the knowledge gaps about Molly by examining whether users differ in substance use outcomes and sensation seeking than nonusers. Specifically, this study tested whether Molly users engaged in heavier use of other substances and experienced more substance-related harms in general than nonusers. Further, the current study investigated whether Molly users exhibited higher levels of sensation seeking than nonusers. Lastly, this study examined whether Molly user status would be associated with substance-related harms beyond the confounding influence of other substance use and trait sensation seeking. METHODS: Participants were 710 (71.9% female) college alcohol drinkers who completed self-report surveys about substance use (i.e., Molly, alcohol, and other drug use), substance-related problems, and sensation seeking. RESULTS: Results revealed that approximately 12% of the sample reported lifetime Molly use. Molly users compared with nonusers reported higher levels of other drug use, alcohol use, substance-related problems, and sensation seeking. Further, Molly users reported experiencing poorer substance use outcomes (e.g., blacking out, academic/occupational problems, and withdrawal symptoms) after accounting for sensation seeking and other substance use. CONCLUSIONS: These findings indicate that Molly users are higher in sensation seeking and that use is uniquely related to greater risk for substance-related harms. These preliminary findings demonstrate a need for correcting possible misperceptions regarding the purity of Molly and educating users on the potential for experiencing associated harms. Such information could be used to develop efficacious prevention programming for college students. PMID- 26820397 TI - Incarcerated Violent Offenders' Ability to Avoid Revealing Their Potential for Violence on the Rorschach and the MMPI-2. AB - Recently, Hartmann and Hartmann (2014) found that psychiatric outpatients, both with and without access to Internet-based information about the Rorschach Inkblot Method (RIM; Weiner, 2003 ) and the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989 ), were unable to imitate healthy test performance on these tests. We replicated the study by administering the RIM and the MMPI-2 to 63 incarcerated violent offenders using similar testing conditions. As in the previous study, comparisons were made not only among the 3 subgroups of incarcerated offenders, but also between these offender groups and the group of nonpatients examined in the previous study. On the RIM, Internet-coached and uncoached "faking good" offenders produced records with significantly higher F% and X-% and significantly lower M, m, SumC, X+%, P, AG, and COP than nonoffenders under standard instructions (effect sizes between d = 0.24 and d = 2.39). For AgC, AgPot, AgPast, and TCI% there were no significant differences between the faking offenders and the nonoffenders under standard instructions. On the MMPI-2 clinical scales, there were no significant differences between the faking good groups and the nonoffenders under standard instructions, except on Hs, Pd, and Sc. Both faking groups were identifiable by their high L scale scores. Although both faking groups managed to avoid giving responses with aggressive and generally psychopathological content on the RIM, they were unable to produce test profiles demonstrating healthy test performance on any of the tests; nevertheless, Internet-based test information might weaken test validity. PMID- 26820398 TI - Metal-based drugs that break the rules. AB - Cisplatin and other platinum compounds have had a huge impact in the treatment of cancers and are applied in the majority of anticancer chemotherapeutic regimens. The success of these compounds has biased the approaches used to discover new metal-based anticancer drugs. In this perspective we highlight compounds that are apparently incompatible with the more classical (platinum-derived) concepts employed in the development of metal-based anticancer drugs, with respect to both compound design and the approaches used to validate their utility. Possible design approaches for the future are also suggested. PMID- 26820399 TI - Hepatitis E Virus Does Not Contribute to Hepatic Decompensation Among Patients With Advanced Chronic Hepatitis C. AB - BACKGROUND & AIMS: Hepatitis E (HEV) can cause acute-on-chronic liver failure in persons with pre-existing liver disease. We investigated whether HEV infection contributes to hepatic decompensation in patients with previously stable, advanced chronic hepatitis C. METHODS: We performed a case-control study using stored serum samples from subjects enrolled in the randomized phase of the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial (n = 1050; mean age, 51 y; 70% male; 40% with cirrhosis at baseline). Cases were subjects who developed hepatic decompensation within a 24-week period. Controls (3 per case) were subjects without hepatic decompensation matched for fibrosis stage and followed up for a similar period. A serum sample obtained within 6 months after the decompensation event in cases and the same follow-up period in controls were tested for anti-HEV IgG. Subjects with a positive result had a baseline sample similarly tested for anti-HEV IgG. We measured levels of anti-HEV IgM and HEV RNA in blood samples from incident cases. RESULTS: Of the 1050 subjects analyzed, 314 (30%) experienced a clinical event. Of the 314 subjects who experienced decompensation as defined, 89 (28%) were tested for anti-HEV, along with 267 controls (without decompensation). Similar proportions of cases and controls tested positive for anti-HEV (22.5% and 20.6%, respectively; P = .70). Ten incident HEV infections were identified-4 in cases (4.5%) and 6 in controls (2.2%) (P = .28). HEV RNA was not detected in blood samples from the 10 incident infections. Only 2 of the 4 incident infections among cases were related temporally to the decompensation event. CONCLUSIONS: HEV does not appear to be a significant cause of hepatic decompensation among persons with previously stable, advanced chronic hepatitis C in the United States. PMID- 26820400 TI - Association of Nonalcoholic Fatty Liver Disease With Visceral Adiposity but Not Coronary Artery Calcification in the Elderly. AB - BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is related closely to risk factors for coronary artery disease, but it is unclear whether NAFLD independently contributes to atherosclerosis. We investigated the association between NAFLD and coronary artery calcium (CAC) scores, determined based on noncontrast cardiac computed tomography data, in an elderly cohort. METHODS: We conducted a longitudinal, cross-sectional study of data from 250 participants (mean age, 67.6 +/- 7.0 y; 43.2% men) in the Rancho Bernardo Study-a prospective population-based study of mostly white adults in suburban Southern California. We compared CAC scores, liver-to-spleen attenuation ratio, and volumes of visceral adipose tissue (VAT) at baseline and after a 5-year follow-up period. RESULTS: We assigned participants to groups based on CAC scores (0, 0-10, 11-100, 101-400, and >400). Among groups, the liver-to-spleen attenuation ratio did not vary significantly, but VAT increased with CAC score (median and interquartile range values were as follows: 50.0 [33.3-77.4] cm(3), 63.0 [33.9-93.1] cm(3), 66.1 [48.2-80.2] cm(3), 69.1 [48.1-85.0] cm(3), 76.1 [53.1-108.5] cm(3) for CAC groups; P = .0054). In multivariable regression analysis, NAFLD at baseline was not associated with an increased risk of a CAC score greater than 0. Longitudinal analysis showed that visceral fat, but not hepatic steatosis, increased in participants with increasing CAC scores (interquartile range 57.1-92.4) vs 55.2 cm(3) in patients without (interquartile range 36.5-81.1, P = .0401). The proportion of patients with NAFLD decreased after the 5-year follow-up period (from 29.3% before to 14.1% afterward; P = .0081), despite increased mean CAC scores and VAT volume in patients. CONCLUSIONS: In adults age 67.6 +/- 7.0 years, the proportion with NAFLD decreased despite increasing CAC score and VAT with age. There was no clear association between NAFLD and CAC score. However, VAT was associated with baseline and increasing CAC scores. Visceral adiposity therefore might be a risk factor for coronary artery disease. PMID- 26820401 TI - Effects of Cirrhosis on Short-term and Long-term Survival of Patients With Hepatitis B-related Hepatocellular Carcinoma. AB - BACKGROUND & AIMS: Hepatitis B virus (HBV) is the most common cause of hepatocellular carcinoma (HCC) worldwide. Unlike other liver diseases, HBV can cause HCC in the absence of cirrhosis. We investigated whether features of HCC in patients with HBV infection without cirrhosis and survival times differ from those of patients who develop HCC after cirrhosis. METHODS: We performed a retrospective cohort study of 487 consecutive cases of HBV-related HCC who were seen from 2000 through 2014 at a tertiary care center. Laboratory values, imaging results, and treatment information were obtained from subjects' medical records. Symptoms of HCC included weight loss, abdominal pain, or new hepatic decompensation. The primary outcome was overall survival, which was categorized as short-term survival (up to 3 years after the diagnosis of HCC) or long-term survival (3-10 years after diagnosis). RESULTS: The mean tumor size at diagnosis was significantly larger in patients without cirrhosis (6.4 +/- 4.3 cm) than in patients with cirrhosis (5.0 +/- 3.8 cm) (P = .0009). A significantly larger proportion of patients without cirrhosis had symptoms at diagnosis (43.8% vs 35.4% in patients without cirrhosis, P = .09). A significantly higher proportion of patients without cirrhosis survived for the long-term (P = .003), but there was no significant difference between groups in short-term survival (P = .37). Notably, the same proportions of asymptomatic patients with and without cirrhosis survived for the short-term (64.3% vs 64.2%, P = .73), but a lower proportion of asymptomatic patients with cirrhosis survived for the long-term (P = .015). In multivariate Cox regression analysis, cirrhosis was an independent predictor of death in 3-10 years (hazard ratio, 3.76; P = .003) but not in less than 3 years (P = .48). Symptoms at diagnosis predicted death within 3 years (hazard ratio, 1.76; P =.006) but not in 3-10 years (P = .15). CONCLUSIONS: Patients with HBV infection and HCC without cirrhosis present with larger tumors, and a larger percentage have symptoms of cancer than patients with cirrhosis. This may indicate that HCC surveillance is less than optimal for patients with HBV infection without cirrhosis. Despite this suboptimal surveillance, patients without cirrhosis have higher long-term survival than those with cirrhosis, especially when asymptomatic at diagnosis. PMID- 26820403 TI - Values From Three-dimensional High-resolution Anorectal Manometry Analysis of Children Without Lower Gastrointestinal Symptoms. AB - BACKGROUND & AIMS: Three-dimensional high-resolution anorectal manometry (3DHRAM) provides a topographic image of pressure along the anal canal. We aimed to determine normal 3DHRAM values in children. METHODS: We performed a prospective study of 61 children (34 male; mean age, 8.28 years) without any symptoms arising from the lower gastrointestinal tract who were evaluated at the Department of Pediatric Gastroenterology and Nutrition, Medical University of Warsaw, Poland. Manometry procedures were performed by using a rigid probe without medication. Pressure within the anal canal and 3D images of sphincters were measured. If possible, squeeze pressure and thresholds of sensation were evaluated. The population was divided into age groups of <5 years, 5-8 years, 9-12 years, and older than 12 years. RESULTS: The mean resting and squeeze sphincter pressures were 83 +/- 23 mm Hg and 191 +/- 64 mm Hg, respectively. The mean length of the anal canal was 2.62 +/- 0.68 cm and correlated with age (r = 0.49, P < .0001). The mean rectal balloon volume to elicit rectoanal inhibitory reflex was 15.7 +/- 10.9 cm(3). The first sensation, urge, and discomfort were observed at balloon volumes of 24.4 +/- 23.98 cm(3), 45.9 +/- 34.55 cm(3), and 91.6 +/- 50.17 cm(3), respectively. The mean resting pressure of the puborectalis muscle was 69 +/- 14 mm Hg, whereas the mean squeeze pressure was 124 +/- 33 mm Hg. There was no statistically significant difference in pressure parameters between age groups. We observed a positive correlation between age and balloon volume needed to elicit discomfort (r = 0.49, P < .001). CONCLUSIONS: In a prospective study, we determined normal values from 3DHRAM analysis of children without symptoms arising from the lower gastrointestinal tract. There were no significant differences in pressure results between children of different sexes or ages. ClinicalTrials.gov number: NCT02236507. PMID- 26820404 TI - Patterns and Limitations of Urban Human Mobility Resilience under the Influence of Multiple Types of Natural Disaster. AB - Natural disasters pose serious threats to large urban areas, therefore understanding and predicting human movements is critical for evaluating a population's vulnerability and resilience and developing plans for disaster evacuation, response and relief. However, only limited research has been conducted into the effect of natural disasters on human mobility. This study examines how natural disasters influence human mobility patterns in urban populations using individuals' movement data collected from Twitter. We selected fifteen destructive cases across five types of natural disaster and analyzed the human movement data before, during, and after each event, comparing the perturbed and steady state movement data. The results suggest that the power-law can describe human mobility in most cases and that human mobility patterns observed in steady states are often correlated with those in perturbed states, highlighting their inherent resilience. However, the quantitative analysis shows that this resilience has its limits and can fail in more powerful natural disasters. The findings from this study will deepen our understanding of the interaction between urban dwellers and civil infrastructure, improve our ability to predict human movement patterns during natural disasters, and facilitate contingency planning by policymakers. PMID- 26820405 TI - The Biosurveillance Analytics Resource Directory (BARD): Facilitating the Use of Epidemiological Models for Infectious Disease Surveillance. AB - Epidemiological modeling for infectious disease is important for disease management and its routine implementation needs to be facilitated through better description of models in an operational context. A standardized model characterization process that allows selection or making manual comparisons of available models and their results is currently lacking. A key need is a universal framework to facilitate model description and understanding of its features. Los Alamos National Laboratory (LANL) has developed a comprehensive framework that can be used to characterize an infectious disease model in an operational context. The framework was developed through a consensus among a panel of subject matter experts. In this paper, we describe the framework, its application to model characterization, and the development of the Biosurveillance Analytics Resource Directory (BARD; http://brd.bsvgateway.org/brd/), to facilitate the rapid selection of operational models for specific infectious/communicable diseases. We offer this framework and associated database to stakeholders of the infectious disease modeling field as a tool for standardizing model description and facilitating the use of epidemiological models. PMID- 26820406 TI - Correlation between Extraocular Muscle Size Measured by Computed Tomography and the Vertical Angle of Deviation in Thyroid Eye Disease. AB - The aim of this study was to investigate extraocular muscle (EOM) volume and cross-sectional area using computed tomography (CT), and to determine the relationship between EOM size and the vertical angle of deviation in thyroid eye disease (TED). Twenty-nine TED patients (58 orbits) with vertical strabismus were enrolled in the study. All patients underwent complete ophthalmic examination including prism, alternate cover, and Krimsky tests. Orbital CT scans were also performed on each patient. Digital image analysis was used to quantify superior rectus (SR) and inferior rectus (IR) muscle cross-sectional areas and volumes. Measurements were compared with those of controls. The correlation between muscle size and degree of vertical angle deviation was evaluated. The mean vertical angle of deviation was 26.2 +/- 4.1 prism diopters. The TED group had a greater maximum cross-sectional area and EOM volume in the SR and IR than the control group (all p<0.001). Area and volume of the IR were correlated with the angle of deviation, but the SR alone did not show a significant correlation. The maximum cross-sectional area and volume of [Right IR + Left SR - Right SR - Left IR] was strongly correlated with the vertical angle of deviation (P<0.001). Quantitative CT of the orbit with evaluation of the area and volume of EOMs may be helpful in anticipating and monitoring vertical strabismus in TED patients. PMID- 26820402 TI - Symptoms of Depression and Anxiety Are Independently Associated With Clinical Recurrence of Inflammatory Bowel Disease. AB - BACKGROUND & AIMS: We examined the relationship between symptoms of depression and anxiety and clinical recurrence of inflammatory bowel disease (IBD) in a large patient cohort. We considered the progression of depression and anxiety over time. METHODS: We collected clinical and treatment data on 2007 adult participants of the Swiss IBD study (56% with Crohn's disease [CD], 48% male) performed in Switzerland from 2006 through 2015. Depression and anxiety symptoms were quantified by using the Hospital Anxiety and Depression Scale. The relationship between depression and anxiety scores and clinical recurrence was analyzed by using survival-time techniques. RESULTS: We found a significant association between symptoms of depression and clinical recurrence over time (for all patients with IBD, P = .000001; for subjects with CD, P = .0007; for subjects with ulcerative colitis, P = .005). There was also a significant relationship between symptoms of anxiety and clinical recurrence over time in all subjects with IBD (P = .0014) and in subjects with CD (P = .031) but not ulcerative colitis (P = .066). CONCLUSIONS: In an analysis of a large cohort of subjects with IBD, we found a significant association between symptoms of depression or anxiety and clinical recurrence. Patients with IBD should therefore be screened for clinically relevant levels of depression and anxiety and referred to psychologists or psychiatrists for further evaluation and treatment. PMID- 26820407 TI - Comparison of direct effects of clinically available vasodilators; nitroglycerin, nifedipine, cilnidipine and diltiazem, on human skeletonized internal mammary harvested with ultrasonic scalpel. AB - Direct vasodilator effects of nitroglycerin, nifedipine, cilnidipine and diltiazem on human skeletonized internal mammary artery graft harvested with ultrasonic scalpel were assessed in the presence of 0.1 or 0.2 uM of noradrenaline. Ring preparations were made of distal end section of the bypass grafts, and those dilated by acetylcholine were used for assessment. Each drug dilated the artery in a concentration-related manner (0.01-10 uM, n = 6 for each drug) with a potency of nitroglycerin > nifedipine = cilnidipine > diltiazem. These results indicate that nitroglycerin can be useful for treating internal mammary artery spasm, that clinical utility of diltiazem may not depend on its vasodilator effect on the bypass graft, and that cilnidipine as well as nifedipine will have anti-spastic action which is in the middle between those of nitroglycerine and diltiazem. PMID- 26820408 TI - Addressing Cryptosporidium Infection among Young Children in Low-Income Settings: The Crucial Role of New and Existing Drugs for Reducing Morbidity and Mortality. PMID- 26820409 TI - Development of an integrated microfluidic solid-phase extraction and electrophoresis device. AB - This study focuses on the design and fabrication of a microfluidic platform that integrates solid-phase extraction (SPE) and microchip electrophoresis (MUCE) on a single device. The integrated chip is a multi-layer structure consisting of polydimethylsiloxane valves with a peristaltic pump, and a porous polymer monolith in a thermoplastic layer. The valves and pump are fabricated using soft lithography to enable pressure-based fluid actuation. A porous polymer monolith column is synthesized in the SPE unit using UV photopolymerization of a mixture consisting of monomer, cross-linker, photoinitiator, and porogens. The hydrophobic, porous structure of the monolith allows protein retention with good through flow. The functionality of the integrated device in terms of pressure controlled flow, protein retention and elution, on-chip enrichment, and separation is evaluated using ferritin (Fer). Fluorescently labeled Fer is enriched ~80-fold on a reversed-phase monolith from an initial concentration of 100 nM. A five-valve peristaltic pump produces higher flow rates and a narrower Fer elution peak than a three-valve pump operated under similar conditions. Moreover, the preconcentration capability of the SPE unit is demonstrated through MUCE of enriched Fer and two model peptides in the integrated system. FA, GGYR, and Fer are concentrated 4-, 12-, and 50-fold, respectively. The loading capacity of the polymer monolith is 56 fmol (25 ng) for Fer. This device lays the foundation for integrated systems that can be used to analyze various disease biomarkers. PMID- 26820410 TI - Genetically engineered livestock for biomedical models. AB - To commemorate Transgenic Animal Research Conference X, this review summarizes the recent progress in developing genetically engineered livestock species as biomedical models. The first of these conferences was held in 1997, which turned out to be a watershed year for the field, with two significant events occurring. One was the publication of the first transgenic livestock animal disease model, a pig with retinitis pigmentosa. Before that, the use of livestock species in biomedical research had been limited to wild-type animals or disease models that had been induced or were naturally occurring. The second event was the report of Dolly, a cloned sheep produced by somatic cell nuclear transfer. Cloning subsequently became an essential part of the process for most of the models developed in the last 18 years and is stilled used prominently today. This review is intended to highlight the biomedical modeling achievements that followed those key events, many of which were first reported at one of the previous nine Transgenic Animal Research Conferences. Also discussed are the practical challenges of utilizing livestock disease models now that the technical hurdles of model development have been largely overcome. PMID- 26820411 TI - Interspecies chimeric complementation for the generation of functional human tissues and organs in large animal hosts. AB - The past decade's rapid progress in human pluripotent stem cell (hPSC) research has generated hope for meeting the rising demand of organ donation, which remains the only effective cure for end-stage organ failure, a major cause of death worldwide. Despite the potential, generation of transplantable organs from hPSCs using in vitro differentiation is far-fetched. An in vivo interspecies chimeric complementation strategy relying on chimeric-competent hPSCs and zygote genome editing provides an auspicious alternative for providing unlimited organ source for transplantation. PMID- 26820412 TI - Advances in genetic engineering of the avian genome: "Realising the promise". AB - This review provides an historic perspective of the key steps from those reported at the 1st Transgenic Animal Research Conference in 1997 through to the very latest developments in avian transgenesis. Eighteen years later, on the occasion of the 10th conference in this series, we have seen breakthrough advances in the use of viral vectors and transposons to transform the germline via the direct manipulation of the chicken embryo, through to the establishment of PGC cultures allowing in vitro modification, expansion into populations to analyse the genetic modifications and then injection of these cells into embryos to create germline chimeras. We have now reached an unprecedented time in the history of chicken transgenic research where we have the technology to introduce precise, targeted modifications into the chicken genome, ranging from; new transgenes that provide improved phenotypes such as increased resilience to economically important diseases; the targeted disruption of immunoglobulin genes and replacement with human sequences to generate transgenic chickens that express "humanised" antibodies for biopharming; and the deletion of specific nucleotides to generate targeted gene knockout chickens for functional genomics. The impact of these advances is set to be realised through applications in chickens, and other bird species as models in scientific research, for novel biotechnology and to protect and improve agricultural productivity. PMID- 26820413 TI - Genetically engineered livestock for agriculture: a generation after the first transgenic animal research conference. AB - At the time of the first Transgenic Animal Research Conference, the lack of knowledge about promoter, enhancer and coding regions of genes of interest greatly hampered our efforts to create transgenes that would express appropriately in livestock. Additionally, we were limited to gene insertion by pronuclear microinjection. As predicted then, widespread genome sequencing efforts and technological advancements have profoundly altered what we can do. There have been many developments in technology to create transgenic animals since we first met at Granlibakken in 1997, including the advent of somatic cell nuclear transfer-based cloning and gene editing. We can now create new transgenes that will express when and where we want and can target precisely in the genome where we want to make a change or insert a transgene. With the large number of sequenced genomes, we have unprecedented access to sequence information including, control regions, coding regions, and known allelic variants. These technological developments have ushered in new and renewed enthusiasm for the production of transgenic animals among scientists and animal agriculturalists around the world, both for the production of more relevant biomedical research models as well as for agricultural applications. However, even though great advancements have been made in our ability to control gene expression and target genetic changes in our animals, there still are no genetically engineered animal products on the market for food. World-wide there has been a failure of the regulatory processes to effectively move forward. Estimates suggest the world will need to increase our current food production 70 % by 2050; that is we will have to produce the total amount of food each year that has been consumed by mankind over the past 500 years. The combination of transgenic animal technology and gene editing will become increasingly more important tools to help feed the world. However, to date the practical benefits of these technologies have not yet reached consumers in any country and in the absence of predictable, science-based regulatory programs it is unlikely that the benefits will be realized in the short to medium term. PMID- 26820414 TI - The transgenic animal platform for biopharmaceutical production. AB - The recombinant production of therapeutic proteins for human diseases is currently the largest source of innovation in the pharmaceutical industry. The market growth has been the driving force on efforts for the development of new therapeutic proteins, in which transgenesis emerges as key component. The use of the transgenic animal platform offers attractive possibilities, residing on the low production costs allied to high productivity and quality of the recombinant proteins. Although many strategies have evolved over the past decades for the generation of transgenic founders, transgenesis in livestock animals generally faces some challenges, mainly due to random transgene integration and control over transgene copy number. But new developments in gene editing with CRISPR/Cas system promises to revolutionize the field for its simplicity and high efficiency. In addition, for the final approval of any given recombinant protein for animal or human use, the production and characterization of bioreactor founders and expression patterns and functionality of the proteins are technical part of the process, which also requires regulatory and administrative decisions, with a large emphasis on biosafety. The approval of two mammary gland-derived recombinant proteins for commercial and clinical use has boosted the interest for more efficient, safer and economic ways to generate transgenic founders to meet the increasing demand for biomedical proteins worldwide. PMID- 26820417 TI - How do Scrabble players encode letter position during reading? AB - BACKGROUND: A number of experiments with skilled adult readers have shown that a transposed-letter pseudoword (e.g., CHOLOCATE) is considerably more word-like than a control replacement-letter pseudoword (e.g., CHOTONATE). For instance, in lexical decision, response times are longer and less accurate for CHOLOCATE than for CHOTONATE (i.e., a transposed-letter effect). METHOD: Here, we examined how letter position coding is attained in individuals who excel in orthographic lexical processing: competitive Scrabble players. To this end, we conducted a lexical decision experiment with two types of pseudowords (transposed-letter vs. replacement-letter pseudowords). RESULTS: Data showed that while the transposed letter effect does occur in expert Scrabble players, the magnitude of the effect is dramatically smaller than in a control group of university students-in particular, for the accuracy data. CONCLUSIONS: The parameters responsible for the flexibility of letter position coding in models of visual word recognition must be modulated by the degree of expertise in orthographic-lexical processing. PMID- 26820415 TI - The production of multi-transgenic pigs: update and perspectives for xenotransplantation. AB - The domestic pig shares many genetic, anatomical and physiological similarities to humans and is thus considered to be a suitable organ donor for xenotransplantation. However, prior to clinical application of porcine xenografts, three major hurdles have to be overcome: (1) various immunological rejection responses, (2) physiological incompatibilities between the porcine organ and the human recipient and (3) the risk of transmitting zoonotic pathogens from pig to humans. With the introduction of genetically engineered pigs expressing high levels of human complement regulatory proteins or lacking expression of alpha-Gal epitopes, the HAR can be consistently overcome. However, none of the transgenic porcine organs available to date was fully protected against the binding of anti-non-Gal xenoreactive natural antibodies. The present view is that long-term survival of xenografts after transplantation into primates requires additional modifications of the porcine genome and a specifically tailored immunosuppression regimen compliant with current clinical standards. This requires the production and characterization of multi-transgenic pigs to control HAR, AVR and DXR. The recent emergence of new sophisticated molecular tools such as Zinc-Finger nucleases, Transcription-activator like endonucleases, and the CRISPR/Cas9 system has significantly increased efficiency and precision of the production of genetically modified pigs for xenotransplantation. Several candidate genes, incl. hTM, hHO-1, hA20, CTLA4Ig, have been explored in their ability to improve long-term survival of porcine xenografts after transplantation into non-human primates. This review provides an update on the current status in the production of multi-transgenic pigs for xenotransplantation which could bring porcine xenografts closer to clinical application. PMID- 26820416 TI - Histone H1 Variants in Arabidopsis Are Subject to Numerous Post-Translational Modifications, Both Conserved and Previously Unknown in Histones, Suggesting Complex Functions of H1 in Plants. AB - Linker histones (H1s) are conserved and ubiquitous structural components of eukaryotic chromatin. Multiple non-allelic variants of H1, which differ in their DNA/nucleosome binding properties, co-exist in animal and plant cells and have been implicated in the control of genetic programs during development and differentiation. Studies in mammals and Drosophila have revealed diverse post translational modifications of H1s, most of which are of unknown function. So far, it is not known how this pattern compares with that of H1s from other major lineages of multicellular Eukaryotes. Here, we show that the two main H1variants of a model flowering plant Arabidopsis thaliana are subject to a rich and diverse array of post-translational modifications. The distribution of these modifications in the H1 molecule, especially in its globular domain (GH1), resembles that occurring in mammalian H1s, suggesting that their functional significance is likely to be conserved. While the majority of modifications detected in Arabidopsis H1s, including phosphorylation, acetylation, mono- and dimethylation, formylation, crotonylation and propionylation, have also been reported in H1s of other species, some others have not been previously identified in histones. PMID- 26820418 TI - Self-deception as a mechanism for the maintenance of drug addiction. AB - BACKGROUND: This study was aimed at: (i) examining levels of self-deception in substance dependent individuals following addiction treatment, and (ii) examining the association between participants’ levels of self-deception and (a) personality disorders, (b) addiction-related beliefs, (c) duration of abstinence, and (d) estimates of craving. METHOD: We administered self-report questionnaires of self-deception and mixtification, and core beliefs related to addiction and craving. The sample comprised 79 outpatients who were consecutively recruited at the Centro Provincial de Drogodependencias in Granada: 87.3% were males and the mean age was 37.68 years old. Thirty-four percent of participants were diagnosed with comorbid personality disorders. RESULTS: Results showed that individuals with substance dependence exhibit elevated scores of self-deception, particularly in the domains of active denial, selective amnesia, projection, and confabulation. Individuals with comorbid personality disorders display greater levels of self-deception compared to individuals without dual diagnosis. CONCLUSIONS: Moreover, there is a significant association between levels of self deception and addiction-related beliefs and craving. In addition, there is a negative association between levels of self-deception and duration of abstinence. PMID- 26820419 TI - Medication and creativity in Attention Deficit Hyperactivity Disorder (ADHD). AB - BACKGROUND: The aim of this study was to determine the effect of methylphenidate (MPH) on creative potential in a group of children with attention deficit disorder with hyperactivity (ADHD). METHOD: A randomized single blind crossover study was performed with 24 children with ADHD, aged between 18 and 96 (M = 10.0, SD = 1.3), evaluating each child's creativity with and without MPH, using the Torrance Tests of Creative Thinking-Figural (TTCT). RESULTS: Children under treatment with MPH showed a lower global Creative Index and lower scores on Fluency, Originality and Creative Strengths, compared to when not under treatment. The capacities for Elaboration, Abstractness of Titles, and Resistance to Closure did not differ whether on or off pharmacological treatment. CONCLUSION: Our finding suggests that is important to take into account the impact that MPH might have on the creative potential of a child with ADHD to develop a more accurate evaluation and to develop better treatment plans. PMID- 26820420 TI - Connectivity of BA46 involvement in the executive control of language. AB - BACKGROUND: Understanding the functions of different brain areas has represented a major endeavor of contemporary neurosciences. Modern neuroimaging developments suggest cognitive functions are associated with networks rather than with specific areas. OBJECTIVES: The purpose of this paper was to analyze the connectivity of Brodmann area (BA) 46 (anterior middle frontal gyrus) in relation to language. METHODS: A meta-analysis was conducted to assess the language network in which BA46 is involved. The DataBase of Brainmap was used; 19 papers corresponding to 60 experimental conditions with a total of 245 subjects were included. RESULTS: Our results suggest the core network of BA46. The localization and modules involved suggest BA46 participation in a "frontal language production system" (or extended Broca's system). The depicted BA46 connectivity is also concordant with a minor role in language semantics and language understanding. CONCLUSION: It was concluded that BA46 plays a central role in the language production system, most likely related to its executive control. PMID- 26820421 TI - Influence of social motivation, self-perception of social efficacy and normative adjustment in the peer setting. AB - BACKGROUND: The first objective of this study was to adapt and test the psychometric properties of the Social Achievement Goal Scale (Ryan & Shim, 2006) in Spanish adolescent students. The second objective sought to analyse the influence of social goals, normative adjustment and self-perception of social efficacy on social adjustment among peers. METHOD: A total of 492 adolescents (54.1% females) attending secondary school (12-17 years; M = 13.8, SD = 1.16) participated in the study. Confirmatory factor analysis and structural equation modelling were performed. RESULTS: The validation confirmed the three-factor structure of the original scale: social development goals, social demonstration approach goals and social demonstration-avoidance goals. The structural equation model indicated that social development goals and normative adjustment have a direct bearing on social adjustment, whereas the social demonstration-approach goals (popularity) and self-perception of social efficacy with peers and teachers exert an indirect influence. CONCLUSIONS: The Spanish version of the Social Achievement Goal Scale (Ryan & Shim, 2006) yielded optimal psychometric properties. Having a positive motivational pattern, engaging in norm-adjusted behaviours and perceiving social efficacy with peers is essential to improving the quality of interpersonal relationships. PMID- 26820422 TI - Intervention in reading processes in pupils with Specific Language Impairment (SLI). AB - BACKGROUND: Children with Specific Language Impairment (SLI) encounter significant difficulties in learning to read. The aim of this research was to determine the efficacy of an intervention program on reading processes (letter identification, lexical processes, syntactic processes and semantic processes) in children with SLI. METHOD: The sample consisted of a total of 34 pupils diagnosed with SLI and 34 children with typical language development. For the selection of the sample, the CELF-3 test, the Peabody test, the Hearing Association and Visual Association subtests of the ITPA and the K-BIT Intelligence test were used. The intervention program consisted of 144 sessions of 40 minutes each, in which oral language activities were combined with other activities related to the automation of basic reading processes and reading sentences and texts. RESULTS: Significant gains were also made in the group of children with SLI versus controls in lexical, syntactic, and semantic reading processes. CONCLUSIONS: A combined program of both oral language and reading skills improves reading achievement in pupils with SLI. PMID- 26820423 TI - Mortality salience, political orientation and minimization of terrorists' secondary emotions. AB - BACKGROUND: From the framework of Terror Management Theory, the objective of the present research is to analyze the effect of mortality salience (MS) on the minimization of Muslim terrorists’ secondary emotions (MSE, which can be understood as a particular kind of dehumanization), as a function of political orientation. METHOD: An experimental design was used, in which the participants (university students, N= 293) were randomly assigned to a control or experimental group, their political orientation was taken note of, and they were asked to attribute emotions to Muslim terrorists. RESULTS: In accordance with the hypotheses, the results indicate that, among those supporting tenets of the political left, MS originates less minimization of secondary emotions of the terrorists (MSE). However, among people who stand on the right, MS inspires greater MSE (that is, a lower attribution of these emotions). CONCLUSIONS: These results support the thesis that the effects of MS are not to be found exclusively in conservative people, and that they do not necessarily imply a conservative shift, but constitute a polarization in previous ideological tendencies or cultural worldview. PMID- 26820424 TI - Infrahumanization in children: An evaluation of 70 terms relating to humanity. AB - BACKGROUND: Research on infrahumanization has revealed that individuals attribute more secondary emotions to the in-group than to the out-group, whose capacity to experience them is denied or restricted. When this bias has been examined in children, researchers have used the same taxonomy of affective terms as that used with adults. The aim of this research is to conduct a normative study that will equip researchers with a taxonomy of humanity attributed to emotional terms specifically for children. METHODS: Three hundred and sixty-three children aged between 11 and 12 responded to several questionnaires containing a total of 70 emotional terms, evaluated in eight dimensions associated with the perception of humanity. RESULTS: Principal component analysis shows that children categorize implicit dimensions associated with humanity differently to adults. CONCLUSIONS: This normative study enables the selection of graded emotional terms in humanity perceived by a child sample, in order to overcome current limitations in research on infrahumanization in children. PMID- 26820425 TI - Coping, rumination and posttraumatic growth in people affected by an earthquake. AB - BACKGROUND: In this article, the evaluation of a structural model that seeks to identify predictors and mediators of posttraumatic growth (PTG) of people affected by a natural disaster is presented. METHOD: The sample was composed of 349 adult men and women who experienced the earthquake and tsunami on February 27, 2010 in Chile. A modeling with structural equations was used, contrasting two predictive models of PTG. The latent variables assessed were subjective severity, social sharing of emotion, intrusive rumination, deliberate rumination, problem focused coping and posttraumatic growth. RESULTS: The best fit was obtained with the model that shows a direct influence of the subjective severity, problem focused coping, and deliberate rumination in the presence of PTG. Problem-focused coping mediated the relation between subjective severity and social sharing with PTG. In turn, deliberate rumination mediated the relation of problem-focused coping and intrusive rumination with PTG. CONCLUSIONS: The results show the relevant role of cognitive processes such as deliberate rumination and behavioral processes such as problem-focused coping in the presence of PTG. PMID- 26820426 TI - Importance of self-efficacy in psychoendocrine responses to competition and performance in women. AB - Cognitive appraisal before competition includes self-efficacy, traditionally defined as motivation and the perceived ability to perform well; presumably, both dimensions would affect the biological response to a contest. We aimed to analyze the role of self-efficacy in the psychobiological response to a competition in women. Forty university students were confronted in pairs on a laboratory competition while hormonal and emotional changes were measured. Our results indicated that self-efficacy was positively related to testosterone levels and positive mood, and also to better performance. These results empirically support the importance of main dimensions of the cognitive appraisal in androgenic and emotional responses to competition. In addition, they emphasize the importance of cognitive processes in this response. In conclusion, the relationship between androgens and self-efficacy may play an important role as a facilitator of performance in competitive settings. PMID- 26820427 TI - Applicability of dual-route reading models to Spanish. AB - Two opposing points of view have been presented with regard to the applicability of the dual-route reading models Spanish. Some authors maintain that, given the transparency of the reading system, non-lexical reading is the strategy followed predominantly by Spanish readers and for that reason these models are not appropriate to explain alexias (acquired dyslexias) in Spanish. Other authors, consider that since several cases of phonological, surface and deep alexia have been reported, dual-route reading models are applicable to Spanish in the same way that to the irregular writing systems. In order to contrast these two points of view, an analysis of the two main factors that influence the reading is made: characteristics of the Spanish orthography and characteristics of the Spanish readers. It is conclude that, (1) Due to its transparency, non-lexical reading represents -as in other transparent orthographies-- the initial reading strategy in Spanish; (2) the "reading threshold" (i.e., time required to become literate) is lower in Spanish because there are no irregular words to learn; (3) as reading experience increases, speed increases and lexical reading becomes used more; (4) Given the characteristics of the Spanish reading system, it is understandable that frequency of deep dyslexia is so low. PMID- 26820428 TI - Traditional scores versus IRT estimates on forced-choice tests based on a dominance model. AB - BACKGROUND: Forced-choice tests (FCTs) were proposed to minimize response biases associated with Likert format items. It remains unclear whether scores based on traditional methods for scoring FCTs are appropriate for between-subjects comparisons. Recently, Hontangas et al. (2015) explored the extent to which traditional scoring of FCTs relates to the true scores and IRT estimates. The authors found certain conditions under which traditional scores (TS) can be used with FCTs when the underlying IRT model was an unfolding model. In this study, we examine to what extent the results are preserved when the underlying process becomes a dominance model. METHOD: The independent variables analyzed in a simulation study are: forced-choice format, number of blocks, discrimination of items, polarity of items, variability of intra-block difficulty, range of difficulty, and correlation between dimensions. RESULTS: A similar pattern of results was observed for both models; however, correlations between TS and true thetas are higher and the differences between TS and IRT estimates are less discrepant when a dominance model involved. CONCLUSIONS: A dominance model produces a linear relationship between TS and true scores, and the subjects with extreme thetas are better measured. PMID- 26820429 TI - A comparison of discriminant logistic regression and Item Response Theory Likelihood-Ratio Tests for Differential Item Functioning (IRTLRDIF) in polytomous short tests. AB - BACKGROUND: Short scales are typically used in the social, behavioural and health sciences. This is relevant since test length can influence whether items showing DIF are correctly flagged. This paper compares the relative effectiveness of discriminant logistic regression (DLR) and IRTLRDIF for detecting DIF in polytomous short tests. METHOD: A simulation study was designed. Test length, sample size, DIF amount and item response categories number were manipulated. Type I error and power were evaluated. RESULTS: IRTLRDIF and DLR yielded Type I error rates close to nominal level in no-DIF conditions. Under DIF conditions, Type I error rates were affected by test length DIF amount, degree of test contamination, sample size and number of item response categories. DLR showed a higher Type I error rate than did IRTLRDIF. Power rates were affected by DIF amount and sample size, but not by test length. DLR achieved higher power rates than did IRTLRDIF in very short tests, although the high Type I error rate involved means that this result cannot be taken into account. CONCLUSIONS: Test length had an important impact on the Type I error rate. IRTLRDIF and DLR showed a low power rate in short tests and with small sample sizes. PMID- 26820430 TI - Psychometric properties of the reading comprehension test ECOMPLEC.Sec. AB - BACKGROUND: ECOMPLEC.Sec is a reading comprehension test for secondary students, conceived from a multidimensional perspective in line with large-scale educational surveys such as PISA or PIRLS. The objective of this study was to validate the theoretical model of ECOMPLEC.Sec. A bifactor model that postulates the existence of a general reading comprehension factor and three specific factors provided a good fit to the data. METHOD: 1,912 adolescents (13-18 years) participated in this study. Data analysis included construct validity via confirmatory factor analysis, and factors were regressed onto observed covariates for the interpretation of the constructs. Reliability was calculated from a non linear SEM in order to justify the interpretability of the observed scale and subscale scores. RESULTS: The bifactor model exhibited a significantly better fit to the data than the second-order model. Furthermore, construct validity analysis suggests the existence of specific reading comprehension factors. Finally, the reliability study also supports the idea of using a total score to obtain a measure of reading comprehension. CONCLUSIONS: ECOMPLEC.Sec displays a valid parsimonious factor structure, as well as metric properties that make it a suitable tool to assess reading comprehension. PMID- 26820431 TI - Validity and reliability of the Spanish version of the Displaced Aggression Questionnaire. AB - BACKGROUND: The Displaced Aggression Questionnaire (DAQ) is an instrument that assesses personality differences in the tendency to displace aggression. This scale is composed of three factors: angry rumination (as affective dimension), revenge planning (as cognitive dimension), and general tendency to engage in displaced aggression (as a behavioral dimension). The present study examined the validity and reliability of the Spanish version of the DAQ. METHOD: The sample consisted of 429 student and non-student participants. RESULTS: The results showed good psychometric properties, and factor analyses revealed a clear three factor structure. Further, preliminary data about associations between DAQ scores and indirect aggression and emotion regulation strategies are shown. CONCLUSIONS: The scale presents adequate evidence for potential use in a Spanish population. We discuss its utility for research on different types of aggression (e.g., domestic abuse). PMID- 26820432 TI - Griffithsin binds to the glycosylated proteins (E and prM) of Japanese encephalitis virus and inhibit its infection. AB - Griffithsin (GRFT) is a broad-spectrum antiviral protein against several glycosylated viruses. In our previous publication, we have shown that GRFT exerted antiviral activity against Japanese encephalitis virus (JEV) infection. Herein, we further elucidated the mechanism by which GRFT inhibits JEV infection in BHK-21 cells. In vitro experiments using Pull-down assay and Co immunoprecipitation (CO-IP) assay showed that GRFT binds to the JEV glycosylated viral proteins, specifically the enveloped (E) and premature (prM) glycoproteins. The binding of GRFT to the JEV was competitively inhibited by increasing concentrations of mannose; in turns abolished anti-JEV activity of GRFT. We suggested that, the binding of GRFT to the glycosylated viral proteins may contribute to its anti-JEV activity. Collectively, our data indicated a possible mechanism by which GRFT exerted its anti-JEV activity. This observation suggests GRFT's potentials in the development of therapeutics against JEV or other flavivirus infection. PMID- 26820433 TI - Genome-wide analysis of differential mRNA expression of Amsacta moorei entomopoxvirus, mediated by the gene encoding a viral protein kinase (AMV197). AB - Insect-born entomopoxviruses (Fam: Poxviridae) are potentially important bio pesticide against insect pests and expression vectors as well as vectors for transient human gene therapies including recombinant viral vaccines. For these reasons, it is necessary to understand the regulatory genes functions to improve its biotechnological potential. Here, we focused on the characterization of serine/threonine (Ser/Thr; ORF AMV197) protein kinase gene from the Amsacta moorei entomopoxvirus (AMEV), the type species of the genus Betaentomopoxvirus. Transcription of the parental and an amv197-null recombinant AMEV was compared by whole-genome gene expression microarray analysis. Blast2GO analysis reflected a broad diversity of upregulated and downregulated genes. Results showed that expression levels of 102 genes (45%) out of 226 tested genes changed significantly in the recombinant AMEV infected cells. Of these transcripts, 72 (70.58%) were upregulated and 30 (29.41%) were downregulated throughout the infection period. Genes involved in DNA repair, replication and nucleotide metabolism, transcription and RNA modification, and protein modification were mostly upregulated at different times in cells infected with the recombinant virus. Furthermore, transcription of all studied cellular genes including metabolism of apoptosis (Nedd2-like caspase, hemolin and elongation factor-1 alpha (ef1a) gene) was downregulated in the absence of amv197. Quantitative real time reverse transcription-PCR confirmed viral transcriptional changes obtained by microarray. The results of this study indicated that the product of amv197 appears to affect the transcriptional regulation of most viral and many cellular genes. Further investigations are, however, needed to narrow down the role of AMV197 throughout the infection process. PMID- 26820434 TI - Complex I function in mitochondrial supercomplexes. AB - This review discusses the functional properties of mitochondrial Complex I originating from its presence in an assembled form as a supercomplex comprising Complex III and Complex IV in stoichiometric ratios. In particular several lines of evidence are presented favouring the concept that electron transfer from Complex I to Complex III is operated by channelling of electrons through Coenzyme Q molecules bound to the supercomplex, in contrast with the hypothesis that the transfer of reducing equivalents from Complex I to Complex III occurs via random diffusion of the Coenzyme Q molecules in the lipid bilayer. Furthermore, another property provided by the supercomplex assembly is the control of generation of reactive oxygen species by Complex I. This article is part of a Special Issue entitled Respiratory Complex I, edited by Volker Zickermann and Ulrich Brandt. PMID- 26820435 TI - Characterization of cosmetic sticks at Xiaohe Cemetery in early Bronze Age Xinjiang, China. AB - Cosmetics have been studied for a long time in the society and culture research, and its consumption is regarded as a cultural symbol of human society. This paper focuses on the analysis of the red cosmetic sticks, found in Xiaohe Cemetery (1980-1450BC), Xinjiang, China. The structure of the red cosmetic sticks was disclosed by SR-MUCT scanning (Synchrotron Radiation Micro-computed Tomography), while the chemical components were characterized by FTIR (Fourier Transform Infrared Spectroscopy), Raman Spectroscopy and Proteomics. The results suggested that the cosmetic sticks were made from the cattle heart and covered with a layer of hematite powders as the pigment. Given the numerous red painted relics in Xiaohe Cemetery, this kind of cosmetic sticks might be used as a primitive form of crayon for makeup and painting. The usage of cattle hearts as cosmetic sticks is firstly reported up to our knowledge, which not only reveals the varied utilizations of cattle in Xiaohe Cemetery but also shows the distinctive religious function. Furthermore, these red cosmetic sticks were usually buried with women, implying that the woman may be the painter and play a special role in religious activities. PMID- 26820437 TI - Ramping up degradation for proliferation. AB - The control of proteasome-mediated protein degradation is thought to occur mainly at the level of polyubiquitylation of the substrate. However, the proteasome can also be regulated directly, as now demonstrated by a study in which DYRK2 mediated phosphorylation of the 19S subunit Rpt3 is found to increase proteasome activity. PMID- 26820436 TI - A twist in zygotic reprogramming. AB - The first hours of mammalian embryogenesis are devoted to extensive epigenetic reprogramming. One hallmark is active demethylation of the paternal genome by Tet (ten-eleven translocation) enzymes. However, the process is now shown to be Tet independent at first, with Tet enzymes only counteracting hitherto underappreciated de novo DNA methylation activity in later zygotic stages. PMID- 26820438 TI - Actin puts the squeeze on Drosophila glue secretion. AB - An actin filament coat promotes cargo expulsion from large exocytosing vesicles, but the mechanisms of coat formation and force generation have been poorly characterized. Elegant imaging studies of the Drosophila melanogaster salivary gland now reveal how actin and myosin are recruited, and show that myosin II forms a contractile 'cage' that facilitates exocytosis. PMID- 26820439 TI - Corrigendum: Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells. PMID- 26820440 TI - A New Strategy for Trichomonas Testing Female Adolescents in the Emergency Department. AB - STUDY OBJECTIVE: Sensitive trichomonas diagnostic testing has become available, including nucleic acid amplification tests (NAATs) and a rapid antigen test. The study purpose was to determine if adding sensitive trichomonas testing to routine female sexually transmitted infection (STI) evaluations would increase trichomonas identification and treatment. DESIGN: Two study time periods. Study time 1 (T1) was used for a retrospective review. Study time 2 (T2) was used for a prospective study. SETTING: Emergency Department. PARTICIPANTS: Symptomatic female patients aged 13-20 years (N = 447). INTERVENTIONS: Implementation of routing trichomonas testing in the Emergency Department during T2. MAIN OUTCOME MEASURES: Trichomonas diagnosis and treatment rates were compared during T1 and T2. RESULTS: During T1 31 of 234 of eligible patients (13%) were trichomonas tested. Laboratory-confirmed trichomonas was identified in 3 of 234 (1.3%). During T2, 212 of 213 of eligible patients (99.5%) were trichomonas-tested; 39 of 212 tested trichomonas-positive (18.4%); 29 of 212 tested rapid trichomonas antigen test-positive (13.6%; P < .001), and 33 of 188 tested trichomonas NAAT positive (15.5%; P < .001). Trichomonas treatment was given to 3 of 3 laboratory confirmed trichomonas cases during T1 (100%) compared with 37 of 39 during T2 (95%; P = .688). During T1, 14 of 17 women who received trichomonas treatment (82.4%) did not have a laboratory-confirmed trichomonas diagnosis and during T2 13 of 52 women without a laboratory-confirmed trichomonas diagnosis (25%) were treated for trichomonas (P < .001). Rapid trichomonas antigen tests and trichomonas NAATs were concordant in 178 of 188 patients (94.6%). CONCLUSION: Incorporating trichomonas rapid antigen tests and NAATs into routine female adolescent STI testing significantly increased the number of laboratory-confirmed adolescent trichomonas diagnosis and treatment and are useful Emergency Department STI screening tools. PMID- 26820442 TI - Excited state and charge-carrier dynamics in perovskite solar cell materials. AB - Organo-metal halide perovskites (OMHPs) have attracted enormous interest in recent years as materials for application in optoelectronics and solar energy conversion. These hybrid semiconductors seem to have the potential to challenge traditional silicon technology. In this review we will give an account of the recent development in the understanding of the fundamental light-induced processes in OMHPs from charge-photo generation, migration of charge carries through the materials and finally their recombination. Our and other literature reports on time-resolved conductivity, transient absorption and photoluminescence properties are used to paint a picture of how we currently see the fundamental excited state and charge-carrier dynamics. We will also show that there is still no fully coherent picture of the processes in OMHPs and we will indicate the problems to be solved by future research. PMID- 26820441 TI - Parents' and Adolescents' Attitudes about Parental Involvement in Clinical Research. AB - STUDY OBJECTIVE: To understand parent and adolescent attitudes toward parental involvement during clinical trials and factors related to those attitudes. DESIGN: As part of a study on willingness to participate in a hypothetical microbicide study, adolescents and their parents were interviewed separately. SETTING: Adolescent medicine clinics in New York City. PARTICIPANTS: There were 301 dyads of adolescents (ages 14-17 years; 62% female; 72% Hispanic) and their parents. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The interview included questions on demographic characteristics, sexual history, and family environment (subscales of the Family Environment Scale) that were associated with attitudes about parental involvement. RESULTS: Factor analysis of the parental involvement scale yielded 2 factors: LEARN, reflecting gaining knowledge about study test results and behaviors (4 items) and PROCEDURE, reflecting enrollment and permissions (4 items). Adolescents endorsed significantly fewer items on the LEARN scale and the PROCEDURE scale indicating that adolescents believed in less parental involvement. There was no significant concordance between adolescents and their own parents on the LEARN scale and the PROCEDURE scale. In final multivariate models predicting attitudes, adolescents who were female and had sexual contact beyond kissing, and non-Hispanic parents had lower LEARN scores. Adolescents who were older, had previous research experience, and reported less moral or religious emphasis in their family had lower PROCEDURE scores; there were no significant predictors for parents in the multivariate analyses. CONCLUSION: Parents wanted greater involvement in the research process than adolescents. Recruitment and retention might be enhanced by managing these differing expectations. PMID- 26820443 TI - Endogenous grouper and barramundi Mx proteins facilitated the clearance of betanodavirus RNA-dependent RNA polymerase. AB - This study confirmed that the infection of nervous necrosis virus (NNV), belonging to the betanodavirus, can induce the expression of endogenous Mx in grouper fin-3 (GF-3), grouper brain (cGB), and barramundi brain (cBB) cells, but not in grouper fin-1 (GF-1) cells. In a co-sedimentation assay, RdRp appeared in the mitochondrial pellet of GF-1 cells without endogenous Mx expression. However, in GF-3, cGB, and cBB cells, RdRp was detected in the nuclear pellet accompanied by endogenous Mx. By immunostaining, RdRp was found to colocalize with not only endogenous Mx but also lysosomes and monodansylcadaverine (MDC)-labeled autophagic vacuoles. In GF-1 cells, the RdRp level continuously increased during 24-72 h post infection (hpi). When endogenous Mx expressed during 24-72 hpi in virus-infected GF-3, cGB, and cBB cells, the RdRp level peaked at 24 hpi but decreased at 48-72 hpi. The degradation of RdRp could be suppressed by treatment with 3-methyladenine (3MA), NH4Cl, and Mx-specific siRNA respectively. After poly I:C transfection, the endogenous Mx level peaked at 3 days post transfection (dpt) and then spontaneously decreased at 5-7 dpt. The poly I:C-indued Mx also colocalized with MDC-labeled autophagic vacuoles at 3 dpt, and its degradation could be inhibited by 3MA or NH4Cl treatments. Therefore, the anti-NNV mechanism of endogenous grouper and barramundi Mx is suggested to sequester RdRp for degradation through autophagy and lysosomes. PMID- 26820445 TI - Prediction of time dependent survival in HF patients after VAD implantation using pre- and post-operative data. AB - Heart failure is one of the most common diseases worldwide. In recent years, Ventricular Assist Devices (VADs) have become a valuable option for patients with advanced HF. Although it has been shown that VADs improve patient survival rates, several complications persist during left VAD (LVAD) support. The stratification scores currently employed are mostly generic, i.e. not specifically built for LVAD patients, and are based on pre-implantation patient data. In this work we apply data mining approaches for the prediction of time dependent survival in patients after LVAD implantation. Moreover, the predictions acquired with the use of pre-implantation data are enriched by employing post-implantation data, i.e. follow-up data. Different clinical scenarios have been depicted and the subsequent conditions are tested in order to identify the optimal set of pre- and post-implant features, as well as the most suitable algorithms for feature selection and prediction. The proposed approach is applied to a real dataset of 71 patients, reporting an accuracy of 84.5%, sensitivity of 87% and specificity of 82%. Based on the reported results, expert cardio-surgeons can be supported in planning the treatment of VAD patients. PMID- 26820446 TI - Eye growth and myopia development: Unifying theory and Matlab model. AB - The aim of this article is to present an updated unifying theory of the mechanisms underlying eye growth and myopia development. A series of model simulation programs were developed to illustrate the mechanism of eye growth regulation and myopia development. Two fundamental processes are presumed to govern the relationship between physiological optics and eye growth: genetically pre-programmed signaling and blur feedback. Cornea/lens is considered to have only a genetically pre-programmed component, whereas eye growth is considered to have both a genetically pre-programmed and a blur feedback component. Moreover, based on the Incremental Retinal-Defocus Theory (IRDT), the rate of change of blur size provides the direction for blur-driven regulation. The various factors affecting eye growth are shown in 5 simulations: (1 - unregulated eye growth): blur feedback is rendered ineffective, as in the case of form deprivation, so there is only genetically pre-programmed eye growth, generally resulting in myopia; (2 - regulated eye growth): blur feedback regulation demonstrates the emmetropization process, with abnormally excessive or reduced eye growth leading to myopia and hyperopia, respectively; (3 - repeated near-far viewing): simulation of large-to-small change in blur size as seen in the accommodative stimulus/response function, and via IRDT as well as nearwork-induced transient myopia (NITM), leading to the development of myopia; (4 - neurochemical bulk flow and diffusion): release of dopamine from the inner plexiform layer of the retina, and the subsequent diffusion and relay of neurochemical cascade show that a decrease in dopamine results in a reduction of proteoglycan synthesis rate, which leads to myopia; (5 - Simulink model): model of genetically pre-programmed signaling and blur feedback components that allows for different input functions to simulate experimental manipulations that result in hyperopia, emmetropia, and myopia. These model simulation programs (available upon request) can provide a useful tutorial for the general scientist and serve as a quantitative tool for researchers in eye growth and myopia. PMID- 26820447 TI - Acanthamoeba and mimivirus interactions: the role of amoebal encystment and the expansion of the 'Cheshire Cat' theory. AB - Acanthamoeba are natural hosts for giant viruses and their life cycle comprises two stages: a trophozoite and a cryptobiotic cyst. Encystment involves a massive turnover of cellular components under molecular regulation. Giant viruses are able to infect only the trophozoite, while cysts are resistant to infection. Otherwise, upon infection, mimiviruses are able to prevent encystment. This review highlights the important points of Acanthamoeba and giant virus interactions regarding the encystment process. The existence of an acanthamoebal non-permissive cell for Acanthamoeba polyphaga mimivirus, the prototype member of the Mimivirus genus, is analyzed at the molecular and ecological levels, and compared to a similar phenomenon previously described for Emiliana huxleyi and its associated phycodnaviruses: the 'Cheshire Cat' escape strategy. PMID- 26820448 TI - De novo transcriptome assembly of Perkinsus olseni trophozoite stimulated in vitro with Manila clam (Ruditapes philippinarum) plasma. AB - The protistan parasite Perkinsus olseni is a deadly causative agent of perkinsosis, a molluscan disease affecting Manila clam (Ruditapes philippinarum), having a significant impact on world mollusc production. Deciphering the underlying molecular mechanisms in R. philippinarum-P. olseni interaction is crucial for controlling this parasitosis. The present study investigated the transcriptional expression in the parasite trophozoite using RNA-seq. Control and treatment (in vitro challenged with Manila clam-plasma) P. olseni trophozoite RNA were extracted and sequenced on the Illumina HiSeq 2000 instrument using a 100-bp paired-end sequencing strategy. Paired reads (64.7 million) were de novo assembled using Trinity, and the resultant transcripts were further clustered using CAP3. The re-constructed P. olseni transcriptome contains 47,590 unique transcripts of which 23,505 were annotated to 9764 unique proteins. A large number of genes were associated with Gene Ontology terms such as stress and immune-response, cell homeostasis, antioxidation, cell communication, signal transduction, signalling and proteolysis. Among annotated transcripts, a preliminary gene expression analysis detected 679 up-regulated and 478 down regulated genes, linked to virulence factors, anti-oxidants, adhesion and immune response molecules. Genes of several metabolic pathways such as DOXP/MEP, FAS II or folate biosynthesis, which are potential therapeutic targets, were identified. This study is the first description of the P. olseni transcriptome, and provides a substantial genomic resource for studying the molecular mechanisms of the host parasite interaction in perkinsosis. In this sense, it is also the first evaluation of the parasite gene expression after challenge with clam extracellular products. PMID- 26820449 TI - Melatonergic ligands: Design, synthesis and pharmacological evaluation of novel series of naphthofuranic derivatives. AB - Following our research for new melatonergic ligands, herein we report the design, synthesis and biological evaluation of new series of naphthofuranic derivatives as MT1 and MT2 ligands. Binding affinity results of the prepared compounds revealed good binding affinities at both melatonin receptor subtypes. Particularly, compound 6a behaved as an MT1 partial agonist and MT2 full agonist and exhibited an excellent binding affinity at MT2 (Ki = 0.09 nM). In addition, lateral chain displacement from position 1 to 2 of the furan core had no effect on the binding affinity at both MT1 and MT2, while elongation of this side chain, led to decreased melatonergic binding affinities. PMID- 26820450 TI - Favorable Outcomes of Open Surgical Repair for Blunt Aortic Injury in the Era of Endovascular Repair. AB - Background Long-term outcomes of open surgical repair with distal aortic perfusion for blunt aortic injury (BAI) remain undefined in this era of preferential thoracic endovascular aortic repair (TEVAR). Methods We retrospectively reviewed data from 31 consecutive patients (23 males; mean age, 46 +/- 16 years) who underwent open surgical repair with distal aortic perfusion for acute BAI between 1998 and 2012 at our center and were followed up for 83 +/- 47 months. Results In the 31 patients studied, BAI was most commonly secondary to traffic accidents (87%), with median accident-to-surgery time of 1 day. It was most commonly (90%) located at the isthmus. All patients had other injuries (injury severity score, 25 +/- 6), 68% of which required surgery. The aorta was approached by left (84%) or bilateral (3%) thoracotomy, or median sternotomy (13%). During aortic cross-clamping (73 +/- 47 minutes), distal aortic perfusion was maintained in all patients by left heart or cardiopulmonary bypass (extracorporeal circulation time, 93 +/- 63 minutes). Circulatory arrest was required in 19% of patients. There was no in-hospital mortality or paraplegia. The estimated 5- and 10-year survival rates were 92 +/- 6% and 80 +/- 12%, respectively. One patient underwent reoperation for aortoesophageal fistula at 75 months postoperatively. Conclusion Open repair with distal aortic perfusion for BAI yielded favorable early and late outcomes, and is thus a viable option even in the era of TEVAR. PMID- 26820451 TI - The plasticity of intrinsic functional connectivity patterns associated with rehabilitation intervention in chronic stroke patients. AB - INTRODUCTION: It has been demonstrated that rehabilitative interventions can promote motor function recovery in stroke patients. However, little is known regarding the neural mechanisms that underlie the rehabilitation treatments. The aim of this study was to investigate the plasticity of intrinsic functional connectivity patterns that are associated with rehabilitation intervention in chronic stroke patients. METHODS: Twelve chronic stroke patients with subcortical lesions in the left motor pathway participated in a 4-week rehabilitation intervention and underwent resting-state functional magnetic resonance imaging (fMRI) scanning before and after the intervention. Both functional connectivity analyses of the ipsilesional (left) primary motor cortex (M1) and measurements of the lateralization index of the connectivity patterns were performed in both the stroke patients and healthy controls (HC). RESULTS: Compared with the HC, the decreased connectivity of the ipsilesional M1 with the contralesional sensorimotor cortex (SMC), bilateral supplementary motor areas, and inferior parietal lobule due to stroke were remarkably restored after the intervention. More specifically, the lateralization index of the bilateral SMC tends to be the normal level. Moreover, comparing post- with pre-intervention, we observed significantly increased connectivity of ipsilesional M1 with the contralesional M1 and medial superior frontal gyrus (mSFG). Additionally, the index of pre intervention connectivity with the contralesional mSFG was positively correlated with motor improvement. CONCLUSION: The impact of rehabilitation intervention on intrinsic functional connectivity patterns throughout the brain was measurable on resting-state fMRI, and systematic assessment of resting-state functional connectivity can provide prognostic insight for later motor improvement. PMID- 26820453 TI - Anxiety and depression symptomatology in adult siblings of individuals with different developmental disability diagnoses. AB - Factors predicting the emotional well-being of adult siblings of those with developmental disability (DD) remain under-researched. In this study adult siblings of individuals with Down's syndrome (DS), autism (ASD), Prader-Willi syndrome (PWS) and those with DD but with unknown aetiology (DUA) were compared with each other and a closely-matched control group to ascertain if sibling disability type made a difference to anxiety and/or depression levels. Also considered was the interactive effect of gender, age, parental and sibling educational attainment levels, socio-economic status and birth order on anxiety and depression outcomes. With the exception of siblings of those with DS, adult siblings of those with ASD, PWS and DUA reported significantly higher levels of anxiety and depression than the control group. There were some predictive effects of the demographic variables upon anxiety and depression but none common to all disability types and no moderating effects of demographic factors were found. Consequently other solutions must be found as to why this important group of people have elevated rates of anxiety and depression in comparison to the general population. PMID- 26820452 TI - A Bioinformatics Approach to the Identification of Variants Associated with Type 1 and Type 2 Diabetes Mellitus that Reside in Functionally Validated miRNAs Binding Sites. AB - The present work is aimed at finding variants associated with Type 1 and Type 2 diabetes mellitus (DM) that reside in functionally validated miRNAs binding sites and that can have a functional role in determining diabetes and related pathologies. Using bioinformatics analyses we obtained a database of validated polymorphic miRNA binding sites which has been intersected with genes related to DM or to variants associated and/or in linkage disequilibrium (LD) with it and is reported in genome-wide association studies (GWAS). The workflow we followed allowed us to find variants associated with DM that also reside in functional miRNA binding sites. These data have been demonstrated to have a functional role by impairing the functions of genes implicated in biological processes linked to DM. In conclusion, our work emphasized the importance of SNPs located in miRNA binding sites. The results discussed in this work may constitute the basis of further works aimed at finding functional candidates and variants affecting protein structure and function, transcription factor binding sites, and non coding epigenetic variants, contributing to widen the knowledge about the pathogenesis of this important disease. PMID- 26820454 TI - Different fixative methods influence histological morphology and TUNEL staining in mouse testes. AB - Society of Toxicologic Pathology has recommended mDF to fix testes since 2002. However, subsequent studies showed that false TUNEL-positive cells were observed in mDF-fixed testes. This study compared the effects of different fixation methods on histology and TUNEL staining in mouse testes. Results showed that fixation for 24 or 36h in mDF provided better morphologic details in untreated testes, but markedly enhanced false TUNEL-positive staining. To optimize the fixation, testes were fixed using mDF for 6h and then PFA for 18h. Interestingly, fixation using mDF/PFA manifested better morphologic details, and rarely caused false TUNEL-positive cells in testes. Finally, we examined germ cell apoptosis in testes using mDF/PFA fixation in cadmium-treated mice. As expected, cadmium triggered germ cell apoptosis which was well visualized in the mDF/PFA fixed testes. Taken together, mDF plus PFA fixation not only minimizes false TUNEL positive cells, but also provides integrated morphologic details in testes. PMID- 26820455 TI - The impact of neonatal exposure to 17alpha-ethynylestradiol on the development of kisspeptin neurons in female rats. AB - Neonatal exposure to 17alpha-ethynylestradiol (EE) at relatively low doses leads to delayed effects characterized by the early onset of age-related anovulation. Kisspeptin neurons in the anteroventral periventricular nucleus (AVPV), located at the anterior hypothalamus, are proposed to play key roles in appearance of these delayed effects after maturation. To understand the initial changes, we investigated Kiss1 mRNA expression in the anterior and posterior hypothalamus before weaning in female rats that received neonatal exposure to EE at various doses (0.002-2000MUg/kg). The level of Kiss1 mRNA in the anterior hypothalamus was decreased from 0.002MUg/kg which did not induce delayed effects. In the posterior hypothalamus, Kiss1 mRNA expression did not differ among the groups except 2000MUg/kg group. These results suggest that neonatal exposure to EE affects the development of kisspeptin neurons and kisspeptin neurons in the AVPV are highly susceptible to neonatal EE treatment. PMID- 26820456 TI - [Architectural modernization of psychiatric hospitals influences the use of coercive measures]. AB - BACKGROUND: Coercive measures are widely applied in psychiatric hospitals as a last resort to prevent patients seriously harming themselves or others, with negative psychological and somatic consequences for those affected. OBJECTIVE: In a naturalistic observational study it was investigated whether relocation of the structural milieu of a psychiatric hospital to an architectonically improved new building influenced the application of coercive measures. MATERIAL AND METHODS: The frequency and duration of coercive measures (e.g. fixation, coercive medication and preventive restraints) were routinely documented and compared in the periods before and after the relocation. RESULTS: After the relocation the utilization of coercive measures was significantly reduced by 48-84 %. CONCLUSION: Despite the limitations of the study design the results suggest that the architectural improvements reduced the application of coercive measures. It is speculated that the positive structural milieu enhanced the well-being of patients and staff and their social relations, which in turn prevented coercive measures. PMID- 26820457 TI - [Guideline-conform psychiatric psychotherapeutic treatment for patients with schizophrenia : A normative evaluation of necessary personnel requirements]. AB - BACKGROUND: Although national treatment guidelines and current publications of the German Federal Joint Committee (Gemeinsamer Bundesausschuss) recommend cognitive behavior therapy for all patients with schizophrenia, the implementation of these recommendations in current inpatient and outpatient treatment is only rudimentary. OBJECTIVES: The aim of this study was to systematically search randomized controlled studies (RCTs), meta-analyses and the guidelines of the German Association for Psychiatry and Psychotherapy, Psychosomatics and Neurology (DGPPN) and the British National Institute for Health and Clinical Excellence (NICE) in order to assess the number of personnel necessary for psychiatric and therapeutic inpatient treatment in line with present guidelines. Moreover, the number of staff required was compared with the personnel resources designated by the German psychiatry personnel regulations (Psych-PV). METHODS: The German and NICE guidelines, RCTs and meta-analyses were analyzed and an adequate weekly treatment plan for an inpatient unit was developed. Moreover, the number of personnel necessary to realize the treatment plan was calculated. RESULTS: In order to realize adequate inpatient treatment approximately 107 min extra for medical psychotherapeutic personnel per patient and week (of which 72 min for psychotherapy) and another 60 min for nursing staff per patient and week are required in addition to the current Psych-PV regulations. Thus, implementation in an open ward with 20 inpatients would require 3.62 positions for physicians, 0.7 positions in psychology and 12.85 positions for nursing staff (including management positions and night shifts). DISCUSSION: These evidence-based recommendations for precise specifications of inpatient treatment should lead to improved inpatient treatment in line with present guidelines. Moreover, outpatients and day patients could be included in this treatment model. The results should be considered in the construction of the future prospective payment system for inpatient psychiatric healthcare in Germany. PMID- 26820458 TI - [Psychiatry as a practical science : Considerations following Wolfgang Wieland (1933-2015)]. AB - In the light of historical and modern criticism of the discipline of psychiatry and psychotherapy as a medical subspecialty, this paper deals with aspects of the theory of medicine as postulated by the physician and philosopher Wolfgang Wieland. According to his contributions medicine is a practical science aiming at establishing rational action. Central to this model is a diagnosis, which helps to subsume individual cases under general principles from which essential therapeutic options can be derived. Hence, psychiatry and psychotherapy become a medical subspecialty by adopting the basic model of medical reasoning and action as described by Wieland. Nevertheless, the limits of such an approach must be taken into consideration. Especially in a psychiatric and psychotherapeutic context it is of particular importance that even when being guided by general principles the responsibility for the personality of each individual patient should be adequately met. Furthermore, attention should be paid to the limits of the subspecialty of psychiatry and psychotherapy as a medical discipline, which also requires a critical analysis of the concept of psychiatric illness. PMID- 26820460 TI - [Brain death and consequences : News from the German Medical Association and Ethics Council]. PMID- 26820461 TI - Let it go: the flexible engagement and disengagement of monitoring processes in a non-focal prospective memory task. AB - Remembering to perform a delayed intention is referred to as prospective memory (PM). In two studies, participants performed an Eriksen flanker task with an embedded PM task (they had to remember to press F1 if a pre-specified cue appeared). In study 1, participants performed a flanker task with either a concurrent PM task or a delayed PM task (instructed to carry out the intention in a later different task). In the delayed PM condition, the PM cues appeared unexpectedly early and we examined whether attention would be captured by the PM cue even though they were not relevant. Results revealed ongoing task costs solely in the concurrent PM condition but no significant task costs in the delayed PM condition showing that attention was not captured by the PM cue when it appeared in an irrelevant context. In study 2, we compared a concurrent PM condition (exactly as in Study 1) to a PM forget condition in which participants were told at a certain point during the flanker task that they no longer had to perform the PM task. Analyses revealed that participants were able to switch off attending to PM cues when instructed to forget the PM task. Results from both studies demonstrate the flexibility of monitoring as evidenced by the presence versus absence of costs in the ongoing flanker task implying that selective attention, like a lens, can be adjusted to attend or ignore, depending on intention relevance. PMID- 26820459 TI - [Minimal cerebral dysfunctions and ADHD in adulthood]. AB - Attention deficit hyperactivity disorder (ADHD) is of great importance not only in children but also in adults; however, despite extensive research there are still many unsolved questions with respect to the diagnosis. Patients not only suffer from attention deficits and hyperactivity but also a variety of other problems, such as dyspraxia, problems with stimulus discrimination, dysgrammatism, legasthenia, or motor coordination problems. Furthermore, there are also psychopathological disorders, such as problems with memory, formal thinking, emotional modulation, drive and vegetative stability, in the sense of a psycho-organic syndrome. Such syndromes have long been known in psychiatry under terms, such as complex capacity disorders, minimal cerebral dysfunction (MCD), minimal brain dysfunction (MBD), mild psycho-organic syndrome, psycho-organic axis syndrome, mild cognitive impairment, developmental disorder and developmental biological syndrome. Etiological data with respect to genetics and early childhood brain trauma support the notion of a psychobiological disorder for complex cerebral dysfunction in the sense of a psycho-organic syndrome. Depending on the individual life and work situation, these additional symptoms of ADHD are in many cases of greater relevance for life adjustment than the core symptoms, depending on the individual life and work situations. The concept of minimal cerebral dysfunction describes the ADHD problem better and has a direct bearing on the diagnosis, therapy and sociomedical care of the patients. PMID- 26820462 TI - PEALut efficacy in mild cognitive impairment: evidence from a SPECT case study! PMID- 26820463 TI - Chronic kidney disease and cognitive impairment in the very old. PMID- 26820464 TI - A Rare Case of a Gastrointestinal Stromal Tumor (GIST) Presenting as a Perforated Meckel's Diverticulum. PMID- 26820465 TI - Isolated Portal Venous Hepatocellular Carcinoma. PMID- 26820466 TI - Icariin inhibits oxidized low-density lipoprotein-induced proliferation of vascular smooth muscle cells by suppressing activation of extracellular signal regulated kinase 1/2 and expression of proliferating cell nuclear antigen. AB - Icariin, a flavonoid isolated from the traditional Chinese herbal medicine Epimedium brevicornum Maxim, has been shown to possess anti-inflammatory, anti oxidant and anti-atherosclerotic activities in vivo and in vitro. The aim of the present study was to investigate the effects of icariin on oxidized low-density lipoprotein (ox-LDL)-induced proliferation of vascular smooth muscle cells (VSMCs) and the possible underlying mechanism. VSMCs were cultured and pre treated with various concentrations of icariin (0, 10, 20 or 40 um) prior to stimulation by ox-LDL (50 ug/ml). Cell proliferation was evaluated by an MTT assay. Flow cytometry was used to study the influence of icariin on the cell cycle. Proliferating cell nuclear antigen (PCNA) expression and phosphorylation levels of extracellular signal-regulated kinase (ERK)1/2 were detected by western blot analysis. The results indicated that icariin significantly inhibited ox-LDL induced proliferation of VSMCs and phosphorylation of ERK1/2. Furthermore, icariin also blocked the ox-LDL-induced cell-cycle progression at G1/S-interphase and downregulated the expression of PCNA in VSMCs. In conclusion, the present study indicated for the first time that icariin reduced the amount of ox-LDL induced proliferation of VSMCs through suppression of PCNA expression and inactivation of ERK1/2. PMID- 26820469 TI - The Escherichia coli yjfP Gene Encodes a Carboxylesterase Involved in Sugar Utilization during Diauxie. AB - BACKGROUND: Acetylation and efflux of carbohydrates during cellular metabolism is a well-described phenomenon associated with a detoxification process to prevent metabolic congestion. It is still unclear why cells discard important metabolizable energy sources in the form of acetylated compounds. METHODS: We describe the purification and characterization of an approximately 28-kDa intracellular carboxylesterase (YjfP) and the analysis of gene and protein expression by qRT-PCR and Western blot. RESULTS: qRT-PCR and Western blot, respectively, showed that yjfP is upregulated during the diauxic lag in cells growing with a mixture of glucose and lactose. The beta-galactosidase activity in the DeltayjfP strain was both delayed and half the magnitude of that of the wild type strain. YjfP-hyperproducing strains displayed a long lag phase when cultured with glucose and then challenged to grow with lactose or galactose as the sole carbon source. CONCLUSION: Our results suggest that YjfP controls the intracellular concentration of acetyl sugars by redirecting them to the main metabolic circuits. Instead of detoxification, we propose that sugar acetylation is utilized by the cell for protection and to prevent the metabolism of a necessary minimal intracellular sugar pool. Those sugars can eventually be exported as a side effect of these mechanisms. PMID- 26820467 TI - Specific Gene Loci of Clinical Pseudomonas putida Isolates. AB - Pseudomonas putida are ubiquitous inhabitants of soils and clinical isolates of this species have been seldom described. Clinical isolates show significant variability in their ability to cause damage to hosts because some of them are able to modulate the host's immune response. In the current study, comparisons between the genomes of different clinical and environmental strains of P. putida were done to identify genetic clusters shared by clinical isolates that are not present in environmental isolates. We show that in clinical strains specific genes are mostly present on transposons, and that this set of genes exhibit high identity with genes found in pathogens and opportunistic pathogens. The set of genes prevalent in P. putida clinical isolates, and absent in environmental isolates, are related with survival under oxidative stress conditions, resistance against biocides, amino acid metabolism and toxin/antitoxin (TA) systems. This set of functions have influence in colonization and survival within human tissues, since they avoid host immune response or enhance stress resistance. An in depth bioinformatic analysis was also carried out to identify genetic clusters that are exclusive to each of the clinical isolates and that correlate with phenotypical differences between them, a secretion system type III-like was found in one of these clinical strains, a determinant of pathogenicity in Gram-negative bacteria. PMID- 26820468 TI - Group V Secretory Phospholipase A2 Is Involved in Tubular Integrity and Sodium Handling in the Kidney. AB - Group V (GV) phospholipase A2 (PLA2) is a member of the family of secreted PLA2 (sPLA2) enzymes. This enzyme has been identified in several organs, including the kidney. However, the physiologic role of GV sPLA2 in the maintenance of renal function remains unclear. We used mice lacking the gene encoding GV sPLA2 (Pla2g5 /-) and wild-type breeding pairs in the experiments. Mice were individually housed in metabolic cages and 48-h urine was collected for biochemical assays. Kidney samples were evaluated for glomerular morphology, renal fibrosis, and expression/activity of the (Na+ + K+)-ATPase alpha1 subunit. We observed that plasma creatinine levels were increased in Pla2g5-/- mice following by a decrease in creatinine clearance. The levels of urinary protein were higher in Pla2g5-/- mice than in the control group. Markers of tubular integrity and function such as gamma-glutamyl transpeptidase, lactate dehydrogenase, and sodium excretion fraction (FENa+) were also increased in Pla2g5-/- mice. The increased FENa+ observed in Pla2g5-/- mice was correlated to alterations in cortical (Na+ + K+) ATPase activity/ expression. In addition, the kidney from Pla2g5-/- mice showed accumulation of matrix in corticomedullary glomeruli and tubulointerstitial fibrosis. These data suggest GV sPLA2 is involved in the maintenance of tubular cell function and integrity, promoting sodium retention through increased cortical (Na+ + K+)-ATPase expression and activity. PMID- 26820471 TI - Editorial. AB - Human aging is characterized by large differences between and within older adults. Numerous factors are known to contribute to these differences, including genetic and immunological, somatic and medical, cognitive and behavioral, psychosocial and experiential, as well as socioeconomic and geospatial conditions. Continuing and expanding the scientific objectives of the Berlin Aging Study, the Berlin Aging Study II (BASE-II) seeks to comprehensively describe phenomena associated with aging and old age and to better understand the multiple different underlying factors and their interactions. To this end, BASE II was established as a multi-institutional project combining and integrating interdisciplinary perspectives ranging from molecular genetics and immunology, geriatric medicine and psychology, to sociology and economics. In this Special Issue, we have compiled seven empirical analyses that feature examples of interdisciplinary insights that BASE-II provides by linking data across multiple levels of analyses at which human functioning and development occur in old age. Here, we provide an overview of the study, note commonalities between BASE-II and earlier studies, and highlight some of its unique qualities. PMID- 26820470 TI - It takes a seasoned bird to be a good listener: communication between the sexes. AB - Birds commonly use sound for communication between the sexes. In many songbird species, only males sing and there are pronounced sex differences in the neural song control circuits. By contrast, the auditory circuitry is largely similar in males and females. Both sexes learn to recognize vocalizations heard as juveniles and this shapes auditory response selectivity. Mating vocalizations are restricted to the breeding season, when sex steroid levels are elevated. Auditory cells, from the ear to the cortex, are hormone sensitive. Estrogens are synthesized in the brain and can modulate the activity of auditory neurons. In species that breed seasonally, elevated levels of estradiol in females transiently enhance their auditory responses to conspecific vocalizations, resulting in sex differences in audition. PMID- 26820472 TI - Major Gastrointestinal Cancer Resections in the Elderly in India: Poised for Future Challenges. AB - BACKGROUND: There are no data on surgical outcomes of major gastrointestinal cancer resections in the expanding Indian oncogeriatric population. METHODS: A prospective database of patients who underwent major gastrointestinal cancer resections during varying time periods (2006-2014) was analyzed retrospectively. RESULTS: Two thousand six hundred and forty three patients with a median age of 53 were analyzed. Four hundred and seventy two (17.9%) patients were aged >=65 years and 235 (8.9%) patients were >=70 years. Mortality rates were not significantly higher in the elderly (>=65 years) or the very elderly (>=70 years) when compared to younger controls, being 2.8 vs. 1.6% (p = 0.09) and 3.0 vs. 1.7% (p = 0.162) respectively. Overall morbidity was similar for patients >=65 or <65 years (24.2 vs. 21.7%, p = 0.253), but was higher in patients >=70 years (29.8 vs. 21.4%, p = 0.003). The incidence of severe complications, however, was not significantly greater in this age group (13.2 vs. 12.5%, p = 0.74). CONCLUSIONS: Major gastrointestinal cancer resections in the elderly Indian population, though uncommon, are safe when performed at experienced high volume centres. These results should serve as a starting point for the gradual development of dedicated oncogeriatric programs in the Indian subcontinent. PMID- 26820474 TI - Dietary, clinical and therapeutic aspects of hypertension. PMID- 26820473 TI - Insights into the interaction of the N-terminal amyloidogenic polypeptide of ApoA I with model cellular membranes. AB - BACKGROUND: About twenty variants of apolipoprotein A-I (ApoA-I) are associated to hereditary systemic amyloidoses. Although the molecular bases of this disease are still largely unknown, it has been hypothesized that ApoA-I proteolysis is a key event in pathogenesis, since it triggers the release of an N-terminal fragment (80-100 residue long) that misfolds to form amyloid deposits in peripheral organs and tissues. It is also known that cell membrane lipids play a key role in the fibrillogenic pathway. In the case of ApoA-I related amyloidosis caused by L174S mutation, the 93-residue N-terminal fragment of ApoA-I ([1 93]ApoA-I) was found to be the major constituent of ex vivo fibrils. METHODS: With the main goal to investigate the interaction of either [1-93]ApoA-I and ApoA I with biomimetic membranes, we set-up an experimental system based on the Raman Tweezers methodology. We tested GUVs composed by two types of zwitterionic lipids with a different fluidity degree, i.e. dioleoylphosphatidylcholine (DOPC) and dipalmitoylphosphatidylcholine (DPPC). RESULTS: We found that [1-93]ApoA-I induces conformational disorder in an ordered lipid bilayer. When interacting with fluid phases, instead, the fragment was found to be able to penetrate the membrane bilayer inducing an alignment of lipid chains. CONCLUSIONS: The interaction features of [1-93]ApoA-I with biomimetic membranes strongly depend on the lipid phase. Full-length ApoA-I was found to have similar effects, even if significantly less pronounced. GENERAL SIGNIFICANCE: Our observations shed light on still largely unknown molecular bases of ApoA-I fibrillogenic domain interaction with membranes. PMID- 26820475 TI - A stop-codon of the phosphodiesterase 11A gene is associated with elevated blood pressure and measures of obesity. AB - OBJECTIVE: To identify stop-codon variants associated with blood pressure (BP). METHODS: Illumina exome chip was genotyped in 5453 individuals of the population based Malmo Diet and Cancer Study. We compared BP levels between carriers and noncarriers of all stop-codon variants found in at least 10 individuals and characterized these further based on literature evidence of functionality. Next, the association to ischemic stroke was evaluated in 2278 cases of ischemic stroke and 5969 controls. RESULTS: We identified 19 stop-codon variants with nominally significant BP associations (P < 0.05). One of these, located in the phosphodiesterase 11A (PDE11A) gene (R307X), has previously been reported to cause loss of PDE11A function and Cushing's syndrome in female carriers. In the Malmo Diet and Cancer Study, 1% of the population carried R307X and had age and sex-adjusted (mean, 95% confidence interval) 5.0, 0.29-9.7 (P = 0.038), and 3.3, 0.83-5.7 (P = 0.009) mmHg higher SBP and DBP than noncarriers and also significantly higher waist circumference and BMI. Among females, carriers of the R307X had age adjusted 8.3, 2.3-14 (P = 0.006) and 4.7, 1.7-7.7 (P = 0.002) mmHg higher SBP and DBP, 4.3, 0.84-7.8 (P = 0.015) cm higher waist circumference and 1.7, 0.30-3.1 (P = 0.018) kg/m higher BMI. In addition, carriers of the R307X mutation had an odds ratio of ischemic stroke of 1.73 (95% confidence interval 1.06-2.82); P = 0.028. CONCLUSION: One percent of the Swedish population carries a PDE11A loss-of-function mutation associated with elevated BP, abdominal obesity, and risk of ischemic stroke. PMID- 26820476 TI - Central proopiomelanocortin but not neuropeptide Y mediates sympathoexcitation and hypertension in fat fed conscious rabbits. AB - OBJECTIVE: High-fat diet (HFD)-induced hypertension in rabbits is neurogenic because of the central sympathoexcitatory actions of leptin. Hypothalamic melanocortin and neuropeptide Y (NPY) neurons are recognized as the major signalling pathways through which leptin exerts its central effects. In this study, we assessed the effects of specific antagonists and agonists to melanocortin and NPY receptors on HFD-induced sympathoexcitation and hypertension. METHODS: Rabbits were instrumented with intracerebroventricular cannula, renal sympathetic nerve activity (RSNA) electrode, and blood pressure telemetry transmitter. RESULTS: After 3 weeks HFD (13.5% fat, n = 12) conscious rabbits had higher RSNA (+3.8 nu, P = 0.02), blood pressure (+8.6 mmHg, P < 0.001) and heart rate (+15 b/min, P = 0.01), and brain-derived neurotrophic factor levels in the hypothalamus compared with rabbits fed a control diet (4.2% fat, n = 11). Intracerebroventricular administration of the melanocortin receptor antagonist SHU9119 reduced RSNA (-2.7 nu) and blood pressure (-8.5 mmHg) in HFD but not control rabbits, thus reversing 100% of the hypertension and 70% of the sympathoexcitation induced by a HFD. By contrast, blocking central NPY Y1 receptors with BVD10 increased RSNA only in HFD rabbits. Intracerebroventricular alpha-melanocortin stimulating hormone increased RSNA and heart rate (P < 0.001) in HFD rabbits but had no effect in control rabbits. CONCLUSION: These findings suggest that obesity-induced hypertension and increased RSNA are dependent on the balance between greater activation of melanocortin signalling through melanocortin receptors and lesser activation of NPY sympathoinhibitory signalling. The amplification of the sympathoexcitatory effects of alpha melanocortin stimulating hormone also indicates that the underlying mechanism is related to facilitation of leptin-melanocortin signalling, possibly involving chronic activation of brain-derived neurotrophic factor. PMID- 26820477 TI - Low-grade albuminuria and incidence of cardiovascular disease and all-cause mortality in nondiabetic and normotensive individuals. AB - BACKGROUND: Recent studies indicate that, in people with diabetes or hypertension and in the general population, low-grade albuminuria (LGA) below the microalbuminuria threshold is a predictor for incidence of cardiovascular disease (CVD) and mortality. However, it remains unclear whether LGA predicts the risk of CVD incidence and death in nondiabetic and normotensive individuals. METHODS: A total of 3599 individuals aged not less than 40 years from the general population who are free of CVD in nondiabetic and normotensive individuals with preserved glomerular filtration rate were followed for CVD incidence and all-cause death. LGA was defined as urinary albumin to creatinine ratio (UACR) less than 30 mg/g. It was examined whether there is an association between LGA and CVD incidence or all-cause death. RESULTS: During the average 5.9 years of follow-up, 61 individuals had first CVD events, and 85 individuals died. The hazard ratios (HRs) for CVD incidence and all-cause death after full adjustment by potential confounders increased significantly in the top tertile of LGA (UACR >= 9.6 mg/g for men, >= 12.0 mg/g for women) compared with the first tertile [HR = 2.79, 95% confidence interval (CI), 1.41-5.52, HR = 1.69, 95% CI, 1.00-2.84, respectively]. Population-attributable fractions of the top tertile of LGA for CVD incidence and all-cause death were 37.9 and 20.1%, respectively. CONCLUSION: In apparently healthy individuals with optimal blood pressure and no diabetes, LGA independently predicts CVD incidence and all-cause death, particularly with the large contribution to the excessive incidence of CVD. PMID- 26820478 TI - Increased myocardial vulnerability to ischemia-reperfusion injury in the presence of left ventricular hypertrophy. AB - OBJECTIVE: Despite its high prevalence among patients suffering myocardial infarction, the significance of left ventricle hypertrophy for infarct size is not known. We asked whether infarct size might be increased by this condition, and whether any such increase might be associated with an increased mitochondrial damage following coronary occlusion. METHODS: Occlusion of the left descending artery in isolated, perfused hearts of SHR-SP (spontaneously hypertensive rat stroke-prone) (left ventricular hypertrophy) or Wistar-Kyoto (WKY) (control) rats was used, followed by reperfusion with or without exendin-4 (Exe-4), a glucagon like peptide-1 receptor agonist. Infarct size relative to area-at-risk was determined. Separately, mitochondria were isolated after global ischemia. Activities of complexes III and IV and amounts of selected complex subunits and cytochromes a, b, c, and c1 were determined. RESULTS: Infarct size (ischemia 35 min and 120 min reperfusion) was 65.8% (+/-3.3%) and 37.1% (+/-3.4%) in the SHR SP and WKY hearts, respectively (P < 0.05). Exe-4 significantly decreased infarct size and hypercontracture in WKY, but not in SHR-SP, hearts. After ischemia 15 min in SHR-SP hearts, Exe-4 reduced the infarct (26.6%, +/-3.8% to 9.3% +/- 1.5%; P < 0.05). Mitochondria from postischemic SHR-SP hearts showed a reduction of complex III (368.1 +/- 37.5 to 175.8 +/- 23.0 nmoles/min * mg; P < 0.05) and complex IV (14.4 +/- 0.22 to 5.8 +/- 0.8 1/s * mg; P < 0.05) activities and decreased amounts of cytochromes a, b, and c. CONCLUSION: Hearts from hypertensive (SHR-SP) rats with left ventricle hypertrophy appeared more vulnerable to ischemia-reperfusion injury, as supported by a more profound infarct development and an earlier loss of postconditioning by Exe-4. Mitochondrial complexes III and IV were identified among possible loci of this increased, hypertrophy-associated vulnerability. PMID- 26820479 TI - Hypertension awareness, treatment, and control among diabetic and nondiabetic individuals in a multiethnic population in the Netherlands: the HELIUS study. AB - OBJECTIVES: There is a paucity of data on hypertension awareness, treatment and control among diabetic adults from different ethnic backgrounds. We assessed ethnic differences in prevalence, awareness, treatment, and control of hypertension among diabetic adults and how they are compared with individuals without diabetes. METHODS: Baseline data from the Healthy Life in an Urban Setting study were used including 12 ,633 adults aged 18-70 years from six ethnic backgrounds in Amsterdam, the Netherlands. Age-sex-adjusted prevalence ratios were used to explore ethnic differences. RESULTS: Among diabetic individuals, African-Surinamese (80.2%; 1.26, 95% confidence interval 1.06-1.51) and Ghanaians (81.7%; 1.40, 1.17-1.68) were more likely than Dutch (69.6%) to have hypertension. There were no significant ethnic differences in the rates of awareness and treatment, but blood pressure (BP) control rates among treated hypertensives were significantly lower in Ghanaians (41.7%; 0.66, 0.45-0.96) and African-Surinamese (28.7%; 0.53, 0.34-0.84) than Dutch (54.1%). Among nondiabetic adults, except Moroccans, all the ethnic minorities had higher prevalence rates of hypertension, awareness (except South-Asian Surinamese and Turks) and treatment than Dutch people. By contrast, BP control rates among treated hypertensives were lower in all ethnic minorities, with the differences being significant for African-Surinamese (42.5%; 0.68, 0.57-0.80), South-Asian Surinamese (41.8%; 0.68, 0.57-0.82), and Ghanaians (35.2%; 0.54, 0.45-0.65). CONCLUSION: Hypertension awareness and treatment rates are similar among ethnic groups in both diabetics and nondiabetics. Adequate BP control remains low among ethnic minorities, particularly among diabetic African origin people. Major effort is needed to improve BP control among diabetic people given the cardiovascular complications associated with uncontrolled BP in this group. PMID- 26820480 TI - Patterns of treatment modifications among newly treated hypertensive patients: does choice of modification strategy affect likelihood of treatment discontinuation? AB - OBJECTIVES: Treatment modifications--addition, uptitration, switching, and downtitration--are necessary to address issues such as unattained blood pressure goals, adverse drug events, drug cost, or patient dissatisfaction which lead to treatment discontinuation. This study assessed the patterns of treatment modifications, and compared the rates of treatment modification and time-to treatment modification across five antihypertensive drug classes (ADCs). Additionally, the association between treatment modification strategies and the likelihood of treatment discontinuation was assessed. METHODS: This is a retrospective cohort study using the BlueCross-BlueShield of Texas commercial claims database (2008-2012). Treatment modifications that occurred within 1 year of starting hypertension treatment were identified. Patients who received treatment modifications were followed for 12 months to determine if and when they discontinued treatment. Cox regression models were used to determine the likelihood of treatment modification and treatment discontinuation. RESULTS: About 48.5% of patients received treatment modifications within 1 year of treatment initiation. Rates of treatment modification were significantly different across ADCs; angiotensin-converting enzyme inhibitor and angiotensin receptor blocker users were less likely to receive treatment modifications compared with other ADCs. Mean time-to-treatment modification was more than 100 days for adding and uptitrating, and more than 140 days for switching and downtitrating. Patients intensifying treatment by adding medications were about 25% (vs. uptitration) and 50% (vs. switching) less likely to discontinue treatment. CONCLUSION: Treatment modifications are common among newly treated hypertensive patients, and the rates vary significantly across ADCs. In the real world, treatment modifications occur much later than the 30-day timeline recommended by guidelines. Addition of drugs may be a preferred approach for intensifying treatment of patients at a high risk of treatment discontinuation. PMID- 26820482 TI - Effect of topical administration of tramadol on corneal wound healing in rats. AB - In this study, we aimed to investigate the effects of topical tramadol administration on corneal wound healing, and examine ophthalmic structures and intraocular pressure 7 days after tramadol administration. The experiments were conducted on eight male Wistar rats (250-300 g). After ophthalmic examination, epithelial cell layers in the central cornea were wounded. Rats received 30 MUL of tramadol hydrochloride in one eye (Group Tramadol) and the same volume of vehicle in the other (Group Control) every 12 h for 7 days. Both eyes were stained with fluorescein dye, photographed, and wound area was calculated every 8 h until complete healing was observed. Eye blink frequency and corneal reflex tests were measured before and after drug administrations. After 7 days, slit lamp biomicroscopy, fundoscopy, Goldmann applanation tonometry, and histological evaluation were performed. There was no difference in the corneal wound healing rates between the tramadol and control groups. Reduction in wound area over time was also similar; group-time interaction was insignificant (F = 738.911; p = 0.225). Tramadol application resulted in blinking and blepharospasm for 30 s, but vehicle did not. Corneal reflex was intact and eye blink frequency test results were similar in all measurement times in both groups. Slit lamp biomicroscopy, fundoscopy, and intraocular pressures were within normal range. Corneal cells appeared unaffected by the repeated doses of tramadol for 7 days. Topical tramadol application on the cornea did not cause any side effect, except for initial temporary blinking and blepharospasm. Corneal wound healing was not affected, either. PMID- 26820483 TI - The Energy Landscape for the Self-Assembly of a Two-Dimensional DNA Origami Complex. AB - While the self-assembly of different types of DNA origami into well-defined complexes could produce nanostructures on which thousands of locations can be independently functionalized with nanometer-scale precision, current assembly processes have low yields. Biomolecular complex formation requires relatively strong interactions and reversible assembly pathways that prevent kinetic trapping. To characterize how these issues control origami complex yields, the equilibrium constants for each possible reaction for the assembly of a heterotetrameric ring, the unit cell of a rectangular lattice, were measured using fluorescence colocalization microscopy. We found that origami interface structure controlled reaction free energies. Cooperativity, measured for the first time for a DNA nanostructure assembly reaction, was weak. Simulations of assembly kinetics suggest assembly occurs via parallel pathways with the primary mechanism of assembly being hierarchical: two dimers form that then bind to one another to complete the ring. PMID- 26820481 TI - Extracellular Vesicle Proteins Associated with Systemic Vascular Events Correlate with Heart Failure: An Observational Study in a Dyspnoea Cohort. AB - BACKGROUND: SerpinF2, SerpinG1, CystatinC and CD14 are involved in inflammatory processes and plasma extracellular vesicle (EV) -levels of these proteins have been reported to be associated with systemic vascular events. Evidence is accumulating that inflammatory processes may play a pivotal role both in systemic vascular events and in heart failure. Therefore, we studied the association between plasma extracellular vesicle SerpinF2-, SerpinG1-, CystatinC and CD14 levels and the occurrence of acute heart failure in patients. METHODS AND RESULT: Extracellular vesicle protein levels of SerpinG1, SerpinF2, CystatinC and CD14 were measured in an observational study of 404 subjects presenting with dysponea at the emergency department (4B-cohort). Plasma extracellular vesicles were precipitated in a total extracellular vesicles (TEX)-fraction and in separate LDL and HDL-subfractions. Extracellular vesicle protein levels were measured with a quantitative immune assay in all 3 precipitates. Out of 404 subjects, 141 (35%) were diagnosed with acutely decompensated heart failure. After correction for confounders (including comorbidities and medications), levels of CD14 in the HDL fraction (OR 1.53, p = 0.01), SerpinF2 in the TEX-and LDL-fraction (ORs respectively 0.71 and 0.65, p<0.05) and SerpinG1 in the TEX-fraction (OR 1.55, p = 0.004) were statistically significantly related to heart failure. Furthermore, extracellular vesicle CD14- and SerpinF2-levels were significantly higher in heart failure patients with preserved ejection fraction than in those with reduced ejection fraction. CONCLUSION: Extracellular vesicle levels of CD14, SerpinG1 and SerpinF2 are associated with the occurrence of heart failure in subjects suspected for acute heart failure, suggesting common underlying pathophysiological mechanisms for heart failure and vascular events. PMID- 26820484 TI - Gene expression of membrane transporters: Importance for prognosis and progression of ovarian carcinoma. AB - Membrane transporters (such as ABCs, SLCs and ATPases) act in carcinogenesis and chemoresistance development, but their relevance for prognosis of epithelial ovarian cancer (EOC) remains poorly understood. We evaluated the gene expression profile of 39 ABC and 12 SLC transporters and three ATPases in EOC tissues and addressed their putative role in prognosis and clinical course of EOC patients. Relative gene expression in a set of primary EOC (n=57) and in control ovarian tissues (n=14) was estimated and compared with clinical data and survival of patients. Obtained data were validated in an independent set of patients (n=60). Six ABCs and SLC22A18 gene were significantly overexpressed in carcinomas when compared with controls, while expression of 12 ABCs, five SLCs, ATP7A and ATP11B was decreased. Expression of ABCA12, ABCC3, ABCC6, ABCD3, ABCG1 and SLC22A5 was higher in high grade serous carcinoma compared with other subtypes. ABCA2 gene expression significantly associated with EOC grade in both sets of patients. Notably, expression level of ABCA9, ABCA10, ABCC9 and SLC16A14 significantly associated with progression-free survival (PFS) of the disease in either pilot or validation sets. ABCG2 level associated with PFS in the pooled set of patients. In conclusion, ABCA2, ABCA9, ABCA10, ABCC9, ABCG2 and SLC16A14 present novel putative markers of EOC progression and together with the revealed relationship between ABCA12, ABCC3, ABCC6, ABCD3, ABCG1 and SLC22A5 expression, and high grade serous type of EOC should be further examined by larger follow-up study. PMID- 26820485 TI - Structural and Biochemical Characterization of a Copper-Binding Mutant of the Organomercurial Lyase MerB: Insight into the Key Role of the Active Site Aspartic Acid in Hg-Carbon Bond Cleavage and Metal Binding Specificity. AB - In bacterial resistance to mercury, the organomercurial lyase (MerB) plays a key role in the detoxification pathway through its ability to cleave Hg-carbon bonds. Two cysteines (C96 and C159; Escherichia coli MerB numbering) and an aspartic acid (D99) have been identified as the key catalytic residues, and these three residues are conserved in all but four known MerB variants, where the aspartic acid is replaced with a serine. To understand the role of the active site serine, we characterized the structure and metal binding properties of an E. coli MerB mutant with a serine substituted for D99 (MerB D99S) as well as one of the native MerB variants containing a serine residue in the active site (Bacillus megaterium MerB2). Surprisingly, the MerB D99S protein copurified with a bound metal that was determined to be Cu(II) from UV-vis absorption, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, and electron paramagnetic resonance studies. X-ray structural studies revealed that the Cu(II) is bound to the active site cysteine residues of MerB D99S, but that it is displaced following the addition of either an organomercurial substrate or an ionic mercury product. In contrast, the B. megaterium MerB2 protein does not copurify with copper, but the structure of the B. megaterium MerB2-Hg complex is highly similar to the structure of the MerB D99S-Hg complexes. These results demonstrate that the active site aspartic acid is crucial for both the enzymatic activity and metal binding specificity of MerB proteins and suggest a possible functional relationship between MerB and its only known structural homologue, the copper binding protein NosL. PMID- 26820486 TI - Adjusting the QRS Duration by Body Mass Index for Prediction of Response to Cardiac Resynchronization Therapy: Does One QRS Size Fit All? AB - BACKGROUND: QRS duration (QRSd) is known to be affected by body weight and length. We tested the hypothesis that adjusting the QRSd by body mass index (BMI) may provide individualization for patient selection and improve prediction of cardiac resynchronization therapy (CRT) response. METHODS: A total of 125 CRT recipients was analyzed to assess functional (>=1 grade reduction in NYHA class) and echocardiographic (>=15% reduction in LVESV) response to CRT at 6 months of implantation. Baseline QRSd was adjusted by BMI to create a QRS index (QRSd/BMI) and tested for prediction of CRT response in comparison to QRSd. RESULTS: Overall, 81 patients (65%) responded to CRT volumetrically. The mean QRS index was higher in CRT responders compared to nonresponders (6.2 +/- 1.1 vs 5.2 +/- 0.8 ms.m(2) /kg, P < 0.001). There was a positive linear correlation between the QRS index and the change in LVESV (r = 0.487, P < 0.001). Patients with a high QRS index (>=5.5 ms.m(2) /kg, derived from the ROC analysis, AUC = 0.787) compared to those with a prolonged QRSd (>=150 ms, AUC = 0.729) had a greater functional (72% vs 28%, P < 0.001) and echocardiographic (80% vs 44%, P < 0.001) improvement at 6 months. QRS index predicted CRT response at regression analysis. CONCLUSIONS: Indexing the QRSd by BMI improves patient selection for CRT by eliminating the influence of body weight and length on QRSd. QRS index is a novel indicator that provides promising results for prediction of CRT response. PMID- 26820487 TI - Benefits of Using CD45RA and CD28 to Investigate CD8 Subsets in Kidney Transplant Recipients. AB - The deleterious role of CD8 T cells in kidney graft outcome has regained interest over the years, and memory T cells are considered as one of the main hurdles to achieve transplantation success. Monitoring the CD8 immune response in transplant recipients involved a heterogeneous combination of markers, but the justification of their choice is rarely stated. Whereas the number of parameters is not an issue in phenotypic analysis, functional assays have to accommodate the cell number with the narrowing of the subset. The aim of the study was to investigate the similarities and differences of the subsets identified using three nomenclatures (CD45RA and CCR7/CD27/CD28) in kidney transplant recipients with stable graft function. We found that all three nomenclatures can identify naive and effector memory (EM) rheumatoid arthritis T cell CD8 with similar features. Whereas CM CD8 could only be documented using CCR7 and CD45RA, the characteristics of EM CD8 will differ according to the nomenclature. We found that the use of the CD45RA and CD28 gives the benefit of examining two EM populations at early and late differentiation states. This systematic comparison provides a cohesive layout of the advantages of using these nomenclature strategies in kidney transplant recipients to guide the choice of their use. PMID- 26820488 TI - Migratory connectivity and effects of winter temperatures on migratory behaviour of the European robin Erithacus rubecula: a continent-wide analysis. AB - Many partially migratory species show phenotypically divergent populations in terms of migratory behaviour, with climate hypothesized to be a major driver of such variability through its differential effects on sedentary and migratory individuals. Based on long-term (1947-2011) bird ringing data, we analysed phenotypic differentiation of migratory behaviour among populations of the European robin Erithacus rubecula across Europe. We showed that clusters of populations sharing breeding and wintering ranges varied from partial (British Isles and Western Europe, NW cluster) to completely migratory (Scandinavia and north-eastern Europe, NE cluster). Distance migrated by birds of the NE (but not of the NW) cluster decreased through time because of a north-eastwards shift in the wintering grounds. Moreover, when winter temperatures in the breeding areas were cold, individuals from the NE cluster also migrated longer distances, while those of the NW cluster moved over shorter distances. Climatic conditions may therefore affect migratory behaviour of robins, although large geographical variation in response to climate seems to exist. PMID- 26820489 TI - The role of soluble and insoluble gastric fluid components in the pathogenesis of obliterative bronchiolitis in rat lung allografts. AB - Repetitive gastric fluid aspirations have been shown to lead to obliterans bronchiolitis (OB), but the component or components of gastric fluid that are responsible are unknown. This study investigates the role of particulates and, separately, soluble material in gastric fluid during the development of OB. Whole gastric fluid (WGF) was collected from male Fischer 344 (F344) rats and separated by centrifugation into particle reduced gastric fluid (PRGF) and particulate components resuspended in normal saline (PNS). Orthotopic left lung transplants from male Wistar-Kyoto rats into F344 rats were performed using a modification of the nonsuture external cuff technique with prolonged cold ischemia. Rats were subjected to weekly aspiration of 0.5 ml/kg of WGF (n = 9), PRGF (n = 10), PNS (n = 9), or normal saline (control, NS; n = 9) for 8 weeks following transplantation. Lung allografts treated with WGF, PRGF, or PNS developed a significantly greater percentage of OB-like lesions compared with the control. No statistical difference was observed when comparing the fibrosis grades or the percentage of OB lesions of WGF, PRGF, and PNS groups, suggesting that both soluble and insoluble components of gastric fluid can promote the development of aspiration-induced OB and fibrosis in lung allografts. PMID- 26820491 TI - Design, Synthesis, and Biological Evaluation of Novel CNS 7056 Derivatives as Sedatives in Rats and Rabbits. AB - A new water-soluble benzodiazepine derivative, CNS 7056 (named as remimazolam), has been undergoing many reactions in recent years to provide an intravenous agent with a predictable fast-onset, short duration of action, and rapid recovery profile. Based on the structure of CNS 7056 with proven activity, seven new CNS 7056 derivatives were designed, and their sedative activities upon mouse, rats, and rabbits were examined. Sedative activities of EL-001~007 were screened. The results indicated that the shorter the side chain at C3 position is, the higher the sedative activity is. EL-001 was chosen as the optimal compound for studies of ED50 , LD50 , latency to LRR and the duration of LRR, and its anesthetic activity was compared with that of CNS 7056 in rats and rabbits. Studies showed that EL-001 is a potent sedative in rodent and lagomorpha, with a short duration of action. Compared with CNS 7056, EL-001 has a shorter period of induction despite a slightly longer sedative duration and recovery time. PMID- 26820492 TI - Control of the Redox Activity of Quantum Dots through Introduction of Fluoroalkanethiolates into Their Ligand Shells. AB - Increasing the fraction of 1H,1H,2H,2H-perfluorodecanethiol (PFDT) in the mixed PFDT/oleate ligand shell of a PbS quantum dot (QD) dramatically reduces the permeability of the ligand shell to alkyl-substituted benzoquinones (s-BQs), as measured by a decrease in the efficiency of collisional photoinduced electron transfer. Replacing only 21% of the oleates on the QD surface with PFDT reduces the yield of photo-oxidation by tetramethyl BQ by 68%. Experiments with s-BQ quenchers of two different sizes reveal that the degree of protection provided by the PFDT-doped monolayer, relative to a decanethiolate (DT)-doped monolayer at similar coverage, is due to both size exclusion (PFDT is larger and more rigid than DT), and the oleophobicity of PFDT. This work demonstrates the usefulness of fluorinated ligands in designing molecule-selective and potentially corrosion inhibiting surface coatings for QDs for applications as robust emitters or high fidelity sensing platforms. PMID- 26820493 TI - Time to unrelated donor leukocyte infusion is longer, but incidence of GVHD and overall survival are similar for recipients of unrelated DLI compared to matched sibling DLI. AB - Donor leukocyte infusion (DLI) is used to treat relapsed leukemia after allogeneic hematopoietic stem cell transplant (HCT). Data comparing outcomes after unrelated DLI (uDLI) to matched sibling DLI (msDLI) are scant. We performed a retrospective analysis to assess differences in time to administer uDLI versus msDLI, and impact on outcomes. Fifty three patients with relapsed acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS) after allogeneic HCT received uDLI (n = 18) or msDLI (n = 35) from 2000 to 2011. Median time from relapse to uDLI request was 15 days (range 0-66). Median time from relapse to uDLI was 56 days versus 40 days for msDLI patients (p = 0.034). 35% of msDLI and 44% of uDLI patients developed acute GVHD (p = 0.50). There was no significant difference in Grade C/D GVHD among uDLI and msDLI (28% and 21%, p = 0.58) or median OS after DLI between uDLI and msDLI (95 versus 75 days, p = 0.76). For patients with relapsed acute leukemia and MDS after allogeneic HCT, time from relapse to uDLI was longer than to msDLI, but incidence of GVHD and overall survival were similar. Access to uDLI does not appear to be a barrier to DLI administration. Outcomes unfortunately remain poor regardless of donor source. PMID- 26820494 TI - Notes from the Field: Ongoing Cholera Outbreak - Kenya, 2014-2016. AB - On January 6, 2015, a man aged 40 years was admitted to Kenyatta National Hospital in Nairobi, Kenya, with acute watery diarrhea. The patient was found to be infected with toxigenic Vibrio cholerae serogroup O1, serotype Inaba. A subsequent review of surveillance reports identified four patients in Nairobi County during the preceding month who met either of the Kenya Ministry of Health suspected cholera case definitions: 1) severe dehydration or death from acute watery diarrhea (more than four episodes in 12 hours) in a patient aged >=5 years, or 2) acute watery diarrhea in a patient aged >=2 years in an area where there was an outbreak of cholera. An outbreak investigation was immediately initiated. A confirmed cholera case was defined as isolation of V. cholerae O1 or O139 from the stool of a patient with suspected cholera or a suspected cholera case that was epidemiologically linked to a confirmed case. By January 15, 2016, a total of 11,033 suspected or confirmed cases had been reported from 22 of Kenya's 47 counties (Table). The outbreak is ongoing. PMID- 26820496 TI - High-Performance Si/SiOx Nanosphere Anode Material by Multipurpose Interfacial Engineering with Black TiO(2-x). AB - Silicon oxides (SiOx) have attracted recent attention for their great potential as promising anode materials for lithium ion batteries as a result of their high energy density and excellent cycle performance. Despite these advantages, the commercial use of these materials is still impeded by low initial Coulombic efficiency and high production cost associated with a complicated synthesis process. Here, we demonstrate that Si/SiOx nanosphere anode materials show much improved performance enabled by electroconductive black TiO(2-x) coating in terms of reversible capacity, Coulombic efficiency, and thermal reliability. The resulting anode material exhibits a high reversible capacity of 1200 mAh g(-1) with an excellent cycle performance of up to 100 cycles. The introduction of a TiO(2-x) layer induces further reduction of the Si species in the SiOx matrix phase, thereby increasing the reversible capacity and initial Coulombic efficiency. Besides the improved electrochemical performance, the TiO(2-x) coating layer plays a key role in improving the thermal reliability of the Si/SiOx nanosphere anode material at the same time. We believe that this multipurpose interfacial engineering approach provides another route toward high performance Si-based anode materials on a commercial scale. PMID- 26820495 TI - Decoding of nonverbal language in alcoholism: A perception or a labeling problem? AB - Alcohol-dependent patients have difficulty recognizing social cues such as emotional facial expressions, prosody, and postures. However, most researchers describing these difficulties rely on labeling tasks. It therefore remains difficult to disentangle genuine emotion-decoding problems from emotion-labeling impairments. In the present study, 35 recently detoxified alcohol-dependent patients were compared with 35 matched controls on four emotion-pairing tasks to explore the distinction between labeling and perceptual abilities. First, 2 tasks were used to assess emotion-labeling ability (labeling task) and working memory (necessary to process emotional stimuli; control matching task). Next, 2 experimental pairing tasks were used to explore unimodal, Face-face or voice voice) and cross-modal, Face-voice or voice-face) matching abilities in the absence of any labeling requirement. Patients had difficulty accurately processing voices in unimodal tasks and correctly matching emotional stimuli in cross-modal tasks. Specifically, they did not correctly identify neutral stimuli in unimodal or cross-modal tasks and did not correctly identify fear in cross modal tasks. Reaction times were also slower in these patients. However, accuracy and reaction time (RT) differences between patients and controls were accounted for by including anxiety and depression scores as covariates in the model. These results suggest that emotion-decoding difficulties observed in recently detoxified alcohol-dependent patients are not due to a specific emotion-labeling impairment, but rather involve perceptual difficulties or later integrative processing steps in the brain. Future studies should directly compare depressed or nondepressed alcohol-dependent patients with depressive patients to disentangle the influences of these highly comorbid disorders on nonverbal language perception. PMID- 26820497 TI - Epidemiology of tuberculosis after kidney transplantation in a developing country. AB - BACKGROUND: Tuberculosis (TB) is a great challenge in kidney transplantation, and is often associated with high morbidity and mortality. The aim of this study was to evaluate the epidemiology, clinical manifestations, and impact of TB in kidney transplant (KT) recipients. METHODS: We performed a retrospective analysis of a cohort of adult KT recipients from 2000 to 2012, with follow-up until July 2014. RESULTS: Among the 1737 KT recipients evaluated, 60 developed TB: a 5% cumulative incidence, and an incidence rate of 589.4 cases/100,000 patient-years. Median time to diagnosis was 13.4 months, with 40% of the cases occurring in the first year. New-onset diabetes was significantly associated with post-transplant TB (P = 0.018). Pulmonary TB represented 78% of the cases, including disseminated disease. Two patients received latent TB treatment and developed active infection. TB was associated with a significant reduction in patient and graft survival (74% vs. 90.2% in 5 years for patient survival, P = 0.001; and 58.6% vs. 80.2% in 5 years for graft survival, P < 0.001). Death and graft loss occurred in the first 6 months after diagnosis in one-third of the patients, 38.8% of them with disseminated disease. Disseminated disease was significantly associated with mortality compared to local disease (41.8% vs. 9.7%, P = 0.035). CONCLUSION: TB continues to be a great challenge in KT, especially in developing countries, with significant impact on patient and graft survival. PMID- 26820498 TI - Listening natively across perceptual domains? AB - Our native tongue influences the way we perceive other languages. But does it also determine the way we perceive nonlinguistic sounds? The authors investigated how speakers of Italian, Turkish, and Persian group sequences of syllables, tones, or visual shapes alternating in either frequency or duration. We found strong native listening effects with linguistic stimuli. Speakers of Italian grouped the linguistic stimuli differently from speakers of Turkish and Persian. However, speakers of all languages showed the same perceptual biases when grouping the nonlinguistic auditory and the visual stimuli. The shared perceptual biases appear to be determined by universal grouping principles, and the linguistic differences caused by prosodic differences between the languages. Although previous findings suggest that acquired linguistic knowledge can either enhance or diminish the perception of both linguistic and nonlinguistic auditory stimuli, we found no transfer of native listening effects across auditory domains or perceptual modalities. (PsycINFO Database Record PMID- 26820499 TI - The d-Prime directive: Assessing costs and benefits in recognition by dissociating mixed-list false alarm rates. AB - It can be difficult to judge the effectiveness of encoding techniques in a within subject design. Consider the production effect-the finding that words read aloud are better remembered than words read silently. In the absence of a baseline, a within-subject production effect in a mixed study list could reflect a benefit of reading aloud, a cost of reading silently, or both. To help interpret within subject data, memory researchers have compared within-subject and between subjects designs, with the between-subjects (i.e., pure list) conditions serving as baselines against which the within-subject (i.e., mixed-list) conditions are compared. In the present article, the authors highlight a shortcoming of using this comparison to assess costs and benefits in recognition. Unlike between subjects experiments where separate false alarm rates are obtained for each condition, the typical within-subject experiment yields a collapsed false alarm rate, which, the authors argue, can potentially bias calculations of memory discrimination (d'). Across 3 experiments that used production as the encoding manipulation, they used a typical mixed-list versus pure-list design (Experiment 1) and then made modifications to this design (Experiments 2 and 3) that yielded separate mixed-list false alarm rates. The results of the latter 2 experiments demonstrated that words that are read aloud in a mixed list have an overall memorial benefit over words that are read aloud in a pure list-both in terms of increased hits and reduced false alarms. The authors frame these results in terms of the distinctiveness heuristic. (PsycINFO Database Record PMID- 26820500 TI - Induction of eEF2-specific antitumor CTL responses in vivo by vaccination with eEF2-derived 9mer-peptides. AB - Eukaryotic elongation factor 2 (eEF2) is an essential factor for protein synthesis. Previous studies have shown that the eEF2 gene was overexpressed and plays an oncogenic role in various types of cancers and that eEF2 gene product elicited both humoral immune responses to produce eEF2-specific IgG autoantibody in cancer-bearing individuals and cellular immune responses to induce eEF2 peptide-specific cytotoxic T lymphocytes (CTLs) in vitro. The purpose of the present study was to induce eEF2-specific, antitumor CTL responses in vivo by vaccination with MHC class I-binding eEF2-derived peptide. First, two mouse MHC class I-restricted eEF2-derived, 9-mer peptides, EF17 (17-25 aa, ANIRNMSVI) and EF180 (180-188 aa, RIVENVNVI) were identified as eEF2-specific CTL peptides, and mice were vaccinated intradermally eight times with either EF17 or EF180 peptide emulsified with Montanide ISA51 adjuvant. Cytotoxicity assay showed that eEF2 specific CTLs were induced in both EF17-and EF180-vaccinated mice, and histological study showed no detectable damage in the organs of these mice. Next, to examine in vivo antitumor effects of eEF2 peptide vaccination in a therapeutic model, mice were vaccinated four times with one each of the two eEF2 peptides at weekly intervals after implantation of eEF2-expressing leukemia cells. The vaccination with eEF2 peptides induced eEF2-specific CTLs and suppressed tumor growth, and disease-free survival was significantly longer in EF180-vaccinated mice compared to control mice. The survival was associated with the robustness of eEF2-specific CTL induction. These results indicate that vaccination with MHC class I-binding eEF2 peptide induced eEF2-targeting, antitumor CTL responses in vivo without damage to normal organs, which provided us a rationale for eEF2 peptide-based cancer immunotherapy. PMID- 26820501 TI - ATP-sensitive K+ channels contribute to the protective effects of exogenous hydrogen sulfide against high glucose-induced injury in H9c2 cardiac cells. AB - Hyperglycemia, as well as diabetes mellitus, has been shown to impair ATP sensitive K+ (KATP) channels in human vascular smooth muscle cells. Hydrogen sulfide (H2S) is also known to be an opener of KATP channels. We previously demonstrated the cardioprotective effects exerted by H2S against high-glucose (HG, 35 mM glucose)-induced injury in H9c2 cardiac cells. As such, we hypothesized that KATP channels play a role in the cardioprotective effects of H2S against HG-induced injury. In this study, to examine this hypothesis, H9c2 cardiac cells were treated with HG for 24 h to establish a model of HG-induced insults. Our findings revealed that treatment of the cells with HG markedly decreased the expression level of KATP channels. However, the decreased expression of KATP channels was reversed by the treatment of the cells with 400 uM sodium hydrogen sulfide (NaHS, a donor of H2S) for 30 min prior to exposure to HG. Additionally, the HG-induced cardiomyocyte injuries, including cytotoxicity, apoptosis, oxidative stress and mitochondrial damage, were ameliorated by treatment with NaHS or 100 uM diazoxide (a mitochondrial KATP channel opener) or 50 uM pinacidil (a non-selective KATP channel opener) for 30 min prior to exposure to HG, as indicated by an increase in cell viability, as well as a decrease in the number of apoptotic cells, the expression of cleaved caspase-3, the generation of reactive oxygen species (ROS) and the dissipation of mitochondrial membrane potential (MMP). Notably, treatment of the H9c2 cardiac cells with 100 uM 5-hydroxydecanoic acid (5-HD, a mitochondrial KATP channel blocker) or 1 mM glibenclamide (Gli, a non-selective KATP channel blocker) for 30 min prior to treatment with NaHS and exposure to HG significantly attenuated the above-mentioned cardioprotective effects exerted by NaHS. Notably, treatment of the cells with 500 uM N-acetyl-L-cysteine (NAC, a scavenger of ROS) for 60 min prior to exposure to HG markedly reduced the HG-induced inhibitory effect on the expression of KATP channels. Taken together, our results suggest that KATP channels play an important role in the cardioprotective effects of exogenous H2S against HG-induced injury. This study also provides novel data demonstraring that there is an antagonistic interaction between ROS and KATP channels in HG-exposed H9c2 cardiac cells. PMID- 26820502 TI - Impaired mitophagy activates mtROS/HIF-1alpha interplay and increases cancer aggressiveness in gastric cancer cells under hypoxia. AB - Mitochondrial autophagy (mitophagy) is a selective form of autophagy and a critical step in excluding mitochondria damaged by stress, including hypoxia. This study aimed to determine whether the integrity of mitophagy affected production of the mitochondrial reactive oxygen species (mtROS), hypoxia inducible factor (HIF)-1alpha expression and aggressive characteristics in GC cells under hypoxia. Three GC cell lines, 44As3, 58As9 and MKN45, were investigated in this study. HIF-1alpha expression was induced in the three GC cell lines under hypoxia, with higher expression observed in 44As3 and 58As9 cells compared with MKN45 cells. Cell survival and invasion abilities under hypoxia were significantly stronger in 44As3 and 58As9 cells than MKN45 cells. Moreover, mtROS accumulated in a time-dependent manner in 44As3 and 58As9 cells, but not in MKN45 cells. ROS scavenger N-acetyl-L-cysteine (NAC) treatment resulted in strong attenuation of HIF-1alpha expression, whereas HIF-1alpha knockdown increased ROS production in the three GC cell lines under hypoxia. These results suggested that the mtROS/HIF-1alpha interplay affected the hypoxia induced cancer aggressiveness. Assessment of mitophagy by LC3-I/II conversion, SQSTM1/p62 degradation and specific fluorescence markers demonstrated that hypoxia-induced mitophagy was observed only in MKN45 cells, while the process was impaired in the other two cell lines. Treatment with the autophagy inhibitor chloroquine conversely increased HIF-1alpha expression, mtROS generation, cell survival and invasion in hypoxic MKN45 cells. The present study revealed a novel mechanism in which the integrity of mitophagy might determine cancer aggressiveness via mtROS/HIF-1alpha interplay in GC cells under hypoxic conditions. PMID- 26820503 TI - Predictive macrosomia birthweight thresholds for adverse maternal and neonatal outcomes. AB - OBJECTIVE: We examined the predictive macrosomia birthweight thresholds for adverse maternal and neonatal outcomes. STUDY DESIGN: This was a multicenter, retrospective cohort study conducted in China. We selected 178 709 singletons weighing >=2500 g with gestational age 37-44 weeks. We categorized macrosomia with two gradations (4000-4499 g and >=4500 g) and compared them with a normosomic reference group of infants with birthweight 2500-3999 g. RESULTS: The risks of obstetric and neonatal complications increased when infants had a birthweight of >=4000 g. The rates of infant mortality, Apgar score <=3 at 5 min, respiratory and neurological disorders rose significantly among neonates weighing >=4500 g. CONCLUSION: A definition of macrosomia as birthweight >=4000 g could be beneficial as an indicator of obstetric and newborn complications, and birthweight >=4500 g might be predictive of severe infant morbidity and mortality risk. PMID- 26820504 TI - A tiered model of substance use severity and life complexity: Potential for application to needs-based planning. AB - BACKGROUND: In order to improve long-term outcomes for individuals with substance use problems, one approach is to adopt a system planning model that considers both addiction severity and life complexities. The tiered approach has been developed and tested to describe systems-level need based on levels of risk and problem severity. METHODS: An existing tiered model was modified to accommodate Australian data, incorporating substance use severity and life complexity. The hypothesis was that tiers would reflect differences in well-being amongst help seekers such that an increase in tier would be associated with a reduction in well-being, suggesting the need for more intensive (and integrated) interventions. The model was tested using 2 data sets of screening data, collected from face-to-face alcohol and other drug (AOD) service (n = 430) and online help (n = 309) seekers, drawn from a larger sample of 2,766 screens. The screen included demographic information and substance use, mental health, and quality of life measures. RESULTS: There was a significant relationship between well-being and tier ranking, suggesting that the model adequately captured elements of severity and complexity that impact on well-being. There were notable differences between the help-seeking populations with a higher proportion of online respondents allocated to lower tiers and more face-to-face respondents allocated to higher tiers. However, there was an overlap in these populations, with more than half of online respondents classified as higher tiers and one fifth of face-to-face respondents classified as lower tiers. This suggests that the model can be used both to assess unmet need in out-of-treatment groups and demand in the absence of dependence in a subpopulation of the face-to-face treatment population. CONCLUSIONS: The tiered model provides a method to understand levels of AOD treatment need and, as part of needs-based planning, may be used to optimize treatment responses and resourcing. PMID- 26820506 TI - The Topographic Organization of Retinal Ganglion Cell Density and Spatial Resolving Power in an Unusual Arboreal and Slow-Moving Strepsirhine Primate, the Potto (Perodicticus potto). AB - The potto (Perodicticus potto) is an arboreal strepsirhine found in the rainforests of central Africa. In contrast to most primates, the potto shows slow moving locomotion over the upper surface of branches, where it forages for exudates and crawling invertebrates with its head held very close to the substrate. Here, we asked whether the retina of the potto displays topographic specializations in neuronal density that correlate with its unusual lifestyle. Using stereology and retinal wholemounts, we measured the total number and topographic distribution of retinal ganglion cells (total and presumed parasol), as well as estimating the upper limits of the spatial resolution of the potto eye. We estimated ~210,000 retinal ganglion cells, of which ~7% (~14,000) comprise presumed parasol ganglion cells. The topographic distribution of both total and parasol ganglion cells reveals a concentric centroperipheral organization with a nasoventral asymmetry. Combined with the upwardly shifted orbits of the potto, this nasoventral increase in parasol ganglion cell density enhances contrast sensitivity and motion detection skywards, which potentially assists with the detection of predators in the high canopy. The central area of the potto occurs ~2.5 mm temporal to the optic disc and contains a maximum ganglion cell density of ~4,300 cells/mm2. We found no anatomical evidence of a fovea within this region. Using maximum ganglion cell density and eye size (~14 mm), we estimated upper limits of spatial resolving power between 4.1 and 4.4 cycles/degree. Despite their reported reliance on olfaction to detect exudates, this level of spatial resolution potentially assists pottos with foraging for small invertebrates and in the detection of predators. PMID- 26820507 TI - A trinuclear ruthenium complex as a highly efficient molecular catalyst for water oxidation. AB - A trinuclear ruthenium complex, 3, was designed and synthesized with the ligand 2,2'-bipyridine-6,6'-dicarboxylic acid (bda) and we found that this complex could function as a highly efficient molecular catalyst for water oxidation in homogeneous systems. This trinuclear molecular water oxidation catalyst, 3, displayed much higher efficiencies in terms of turnover numbers and initial oxygen evolution rate than its counterparts, a binuclear catalyst, 2, and a mononuclear catalyst, 1, in both chemically driven and photochemically driven water oxidation based on either the whole catalytic molecules or just the active Ru centers. The reasons for the superior performance of catalyst 3 were discussed and we believe that multiple Ru centers in a single molecule are indeed beneficial for increasing the probability of the formation of O-O bonds through an intramolecular radical coupling pathway. PMID- 26820508 TI - Methanol-induced toxic optic neuropathy with diffusion weighted MRI findings. AB - We report a 52-year-old man with methanol intoxication who showed optic nerve damage as assessed by magnetic resonance imaging (MRI). He was admitted to the hospital with blurred vision after the consumption of alcohol (600-700 ml of cologne). He was treated with intravenous ethanol, NaHCO3 and hemodialysis. On admission, a brain and orbital MRI was performed. Bilateral mild contrast enhancement was detected on the contrast-enhanced images in the retrobulbar segment of the optic nerves (RBONs). Also, diffusion-weighted images showed restricted diffusion in the RBONs. Diagnosis was considered as methanol-induced optic neuropathy based on the MRI findings of the optic nerves. PMID- 26820509 TI - Femoral implantation and pull through as an adjunct to traditional methods in cardiac resynchronization therapy. AB - BACKGROUND: We have described the use of femoral access followed by pull through of the lead to a pectoral position to circumvent difficulty in implanting a left ventricular (LV) lead by standard methods. OBJECTIVE: The purpose of this study was to establish the effect of femoral implantation and pull through on the overall rate of success in percutaneous implantation of LV leads. METHODS: We collected data prospectively in all attempts at LV lead implantation from the time that we envisioned the femoral pull-through approach. RESULTS: In the 6 years to September 30, 2014, our group attempted to implant a new LV lead in 736 patients, including 16 who previously had failed attempts by other groups. A standard superior approach was successful in 726 of 731 patients (99.3%) in whom it was attempted. In 5 patients (0.7%), we failed to deliver a lead from a superior approach; in 5 of 16 patients, with previous failed attemtps (31%), we judged that those attempts had been exhaustive. In all 10 cases, LV lead placement was achieved from a femoral approach, with the procedure time being 186 +/- 65 minutes. In the first case attempted, the pull through failed; the lead was tunneled to the pectoral generator. In 1 case, the coronary sinus was found to be occluded at the ostium: a transseptal approach was used with the subsequent pull through. No complication occurred. At 22.3 +/- 18.5 months after the implantation, all systems implanted by a femoral approach continued to function. CONCLUSION: Used as an adjunct to standard methods, the femoral access and pull through method allows percutaneous LV lead placement in virtually all cases. PMID- 26820511 TI - Mitochondria, contractile apparatus, and ion channels in the failing myocardium: Special relationships or dangerous liaisons? PMID- 26820510 TI - Cellular and ionic mechanisms underlying the effects of cilostazol, milrinone, and isoproterenol to suppress arrhythmogenesis in an experimental model of early repolarization syndrome. AB - BACKGROUND: Early repolarization syndrome (ERS) is associated with polymorphic ventricular tachycardia (PVT) and ventricular fibrillation, leading to sudden cardiac death. OBJECTIVE: The present study tests the hypothesis that the transient outward potassium current (Ito)-blocking effect of phosphodiesterase-3 (PDE-3) inhibitors plays a role in reversing repolarization heterogeneities responsible for arrhythmogenesis in experimental models of ERS. METHODS: Transmembrane action potentials (APs) were simultaneously recorded from epicardial and endocardial regions of coronary-perfused canine left ventricular (LV) wedge preparations, together with a transmural pseudo-electrocardiogram. The Ito agonist NS5806 (7-15 MUM) and L-type calcium current (ICa) blocker verapamil (2-3 MUM) were used to induce an early repolarization pattern and PVT. RESULTS: After stable induction of arrhythmogenesis, the PDE-3 inhibitors cilostazol and milrinone or isoproterenol were added to the coronary perfusate. All were effective in restoring the AP dome in the LV epicardium, thus abolishing the repolarization defects responsible for phase 2 reentry and PVT. Arrhythmic activity was suppressed in 7 of 8 preparations by cilostazol (10 MUM), 6 of 7 by milrinone (2.5 MUM), and 7 of 8 by isoproterenol (0.1-1 MUM). Using voltage clamp techniques applied to LV epicardial myocytes, both cilostazol (10 MUM) and milrinone (2.5 MUM) were found to reduce Ito by 44.4% and 40.4%, respectively, in addition to their known effects to augment ICa. CONCLUSION: Our findings suggest that PDE-3 inhibitors exert an ameliorative effect in the setting of ERS by producing an inward shift in the balance of current during the early phases of the epicardial AP via inhibition of Ito as well as augmentation of ICa, thus reversing the repolarization defects underlying the development of phase 2 reentry and ventricular tachycardia/ventricular fibrillation. PMID- 26820512 TI - The Worst-Case Weighted Multi-Objective Game with an Application to Supply Chain Competitions. AB - In this paper, we propose a worst-case weighted approach to the multi-objective n person non-zero sum game model where each player has more than one competing objective. Our "worst-case weighted multi-objective game" model supposes that each player has a set of weights to its objectives and wishes to minimize its maximum weighted sum objectives where the maximization is with respect to the set of weights. This new model gives rise to a new Pareto Nash equilibrium concept, which we call "robust-weighted Nash equilibrium". We prove that the robust weighted Nash equilibria are guaranteed to exist even when the weight sets are unbounded. For the worst-case weighted multi-objective game with the weight sets of players all given as polytope, we show that a robust-weighted Nash equilibrium can be obtained by solving a mathematical program with equilibrium constraints (MPEC). For an application, we illustrate the usefulness of the worst-case weighted multi-objective game to a supply chain risk management problem under demand uncertainty. By the comparison with the existed weighted approach, we show that our method is more robust and can be more efficiently used for the real world applications. PMID- 26820513 TI - A Comparative Analysis of the Molecular Features of MANF and CDNF. AB - Cerebral dopamine neurotrophic factor (CDNF) is a paralogous protein of mesencephalic astrocyte-derived neurotrophic factor (MANF). Both proteins have been reported to show a common cytoprotective effect on dopaminergic neurons as a secretory protein containing the KDEL-like motif of the ER retrieval signal at the C-terminus, RTDL in MANF and [Q/K]TEL in CDNF among many species, although functions of paralogous proteins tend to differ from each other. In this study, we focused on post-translational regulations of their retention in the endoplasmic reticulum (ER) and secretion and performed comparative experiments on characterization of mouse MANF and mouse CDNF according to our previous report about biosynthesis and secretion of mouse MANF using a NanoLuc system. In this study, co-expression of glucose-regulated protein 78 kDa (GRP78), KDEL receptor 1 or mutant Sar1 into HEK293 cells similarly decreased MANF and CDNF secretion with some degree of variation. Next, we investigated whether CDNF affects the secretion of mouse cysteine-rich with EGF-like domains 2 (CRELD2) because mouse wild-type (wt) MANF but not its KDEL-like motif deleted mutant (DeltaCMANF) was found to promote the CRELD2 release from the transfected cells. Co-expressing CRELD2 with wt or DeltaC CDNF, we found that CDNF and DeltaCMANF hardly elevated the CRELD2 secretion. We then investigated effects of the four or six C-terminal amino acids of MANF and CDNF on the CRELD2 secretion. As a result, co transfection of mouse CDNF having the mouse MANF-type C-terminal amino acids (CDNFRTDL and CDNFSARTDL) increased the CRELD2 secretion to a small extent, but mouse CDNF having human CDNF-type ones (CDNFKTEL and CDNFHPKTEL) well increased the CRELD2 secretion. On the other hand, the replacement of C-terminal motifs of mouse MANF with those of mouse CDNF (MANFQTEL and MANFYPQTEL) enhanced the CRELD2 secretion, and the mouse MANF having human CDNF-type ones (MANFKTEL and MANFHPKTEL) dramatically potentiated the CRELD2 secretion. These results indicate that the secretion of mouse MANF and mouse CDNF is fundamentally regulated in the same manner and that the variation of four C-terminal amino acids in the MANF and CDNF among species might influence their intracellular functions. This finding could be a hint to identify physiological functions of MANF and CDNF. PMID- 26820515 TI - Successful endoscopic ablation of a pyriform sinus fistula in a child: case report and literature review. AB - Recurrent thyroid infections are rare in children. When present, patients should be evaluated for anatomic anomalies such as pyriform sinus fistulae. We describe a 12-year-old girl with history of recurrent thyroid abscesses secondary to a pyriform sinus fistula and managed with concurrent endoscopic ablation and incision and drainage. PMID- 26820514 TI - Control of Somatosensory Cortical Processing by Thalamic Posterior Medial Nucleus: A New Role of Thalamus in Cortical Function. AB - Current knowledge of thalamocortical interaction comes mainly from studying lemniscal thalamic systems. Less is known about paralemniscal thalamic nuclei function. In the vibrissae system, the posterior medial nucleus (POm) is the corresponding paralemniscal nucleus. POm neurons project to L1 and L5A of the primary somatosensory cortex (S1) in the rat brain. It is known that L1 modifies sensory-evoked responses through control of intracortical excitability suggesting that L1 exerts an influence on whisker responses. Therefore, thalamocortical pathways targeting L1 could modulate cortical firing. Here, using a combination of electrophysiology and pharmacology in vivo, we have sought to determine how POm influences cortical processing. In our experiments, single unit recordings performed in urethane-anesthetized rats showed that POm imposes precise control on the magnitude and duration of supra- and infragranular barrel cortex whisker responses. Our findings demonstrated that L1 inputs from POm imposed a time and intensity dependent regulation on cortical sensory processing. Moreover, we found that blocking L1 GABAergic inhibition or blocking P/Q-type Ca2+ channels in L1 prevents POm adjustment of whisker responses in the barrel cortex. Additionally, we found that POm was also controlling the sensory processing in S2 and this regulation was modulated by corticofugal activity from L5 in S1. Taken together, our data demonstrate the determinant role exerted by the POm in the adjustment of somatosensory cortical processing and in the regulation of cortical processing between S1 and S2. We propose that this adjustment could be a thalamocortical gain regulation mechanism also present in the processing of information between cortical areas. PMID- 26820517 TI - Sirtuins 1 and 2 Are Universal Histone Deacetylases. AB - Lysine acetylation serves as an epigenetic marker for myriad cellular processes, such as signaling, differentiation, DNA repair, angiogenesis, and the like. Sirtuin 1 (SIRT1) and sirtuin 2 (SIRT2) are NAD(+)-dependent histone deacetylases that operate as post-translational regulators for the deacetylation of acetyllysine. Here, we discuss the ability for SIRT1 and SIRT2 to deacetylate monoacetylated histone H3 on two separate architectures-the peptide and the nucleosome. In addition, we analyze the site-specificity of SIRT1 and SIRT2 on 10 different monoacetylated histone H3 nucleosomes. By utilizing a rapid screening array, SIRT1 and SIRT2 were found to demonstrate heightened enzymatic activity when incubated with nucleosomal substrates over their peptide counterparts. These two enzymes displayed little site-specificity among the acetyl-nucleosomes screened, contrary to previous expectations, as well. The implication of the overall nonspecificity of SIRT1 and SIRT2 on the nucleosome suggests that these sirtuin enzymes have an adaptive nature, harnessing an ability to respond to various cellular situations, rather than an enzyme specifically designed for a particular task or function. PMID- 26820516 TI - 3D Architecture of the Trypanosoma brucei Flagella Connector, a Mobile Transmembrane Junction. AB - BACKGROUND: Cellular junctions are crucial for the formation of multicellular organisms, where they anchor cells to each other and/or supportive tissue and enable cell-to-cell communication. Some unicellular organisms, such as the parasitic protist Trypanosoma brucei, also have complex cellular junctions. The flagella connector (FC) is a three-layered transmembrane junction that moves with the growing tip of a new flagellum and attaches it to the side of the old flagellum. The FC moves via an unknown molecular mechanism, independent of new flagellum growth. Here we describe the detailed 3D architecture of the FC suggesting explanations for how it functions and its mechanism of motility. METHODOLOGY/PRINCIPAL FINDINGS: We have used a combination of electron tomography and cryo-electron tomography to reveal the 3D architecture of the FC. Cryo electron tomography revealed layers of repetitive filamentous electron densities between the two flagella in the interstitial zone. Though the FC does not change in length and width during the growth of the new flagellum, the interstitial zone thickness decreases as the FC matures. This investigation also shows interactions between the FC layers and the axonemes of the new and old flagellum, sufficiently strong to displace the axoneme in the old flagellum. We describe a novel filament, the flagella connector fibre, found between the FC and the axoneme in the old flagellum. CONCLUSIONS/SIGNIFICANCE: The FC is similar to other cellular junctions in that filamentous proteins bridge the extracellular space and are anchored to underlying cytoskeletal structures; however, it is built between different portions of the same cell and is unique because of its intrinsic motility. The detailed description of its structure will be an important tool to use in attributing structure / function relationships as its molecular components are discovered in the future. The FC is involved in the inheritance of cell shape, which is important for the life cycle of this human parasite. PMID- 26820519 TI - A lipid nanoparticle for the efficient delivery of siRNA to dendritic cells. AB - Applying small interfering RNA (siRNA) to dendritic cell (DC) based therapy represents a potential candidate for cancer immunotherapy. However, delivering siRNA to DCs is a challenging issue for non-viral vectors. To date, only viral vectors have achieved efficient gene silencing in DCs. We report herein that a novel cationic lipid, YSK12-C4, when loaded in a nanoparticle with siRNA (YSK12 C4 multifunctional envelope type nano device [YSK12-MEND]), greatly facilitated gene silencing in mouse DCs. The use of the YSK12-MEND resulted in a gene silencing efficiency in excess of 90%, with a median effective dose (ED50) of 1.5nM, whereas the maximum gene silencing efficiency of Lipofectamine RNAiMAX was less than 60% and the ED50 was 25nM. Furthermore, suppressor of cytokine signaling 1, an immune suppressive molecule in DCs, silenced in the mouse DC by the YSK12-MEND showed a drastic enhancement in cytokine production, resulting in the significant suppression of tumor growth when it was applied to DC-based therapy against a mouse lymphoma. These results clearly indicate that YSK12-MEND overcomes the obstacle associated with non-viral vectors and can be considered to be a promising non-viral vector for siRNA delivery to DCs, thus accelerating DC based therapies with siRNA. PMID- 26820518 TI - Effects of adipose-derived stem cells plus insulin on erectile function in streptozotocin-induced diabetic rats. AB - PURPOSE: Erectile dysfunction (ED) is a distressing complication in men with diabetes mellitus (DM). This study aimed to investigate the effects of adipose derived stem cells (ADSCs) plus insulin on ED in streptozotocin (STZ)-induced diabetic rats. METHODS: Forty-five eight-week-old male Sprague-Dawley rats received intraperitoneal injection of STZ (60 mg/kg). Eight weeks after the induction, the determined diabetic rats were randomly distributed into four groups: rats in DM + PBS group received a one-time intracavernous (IC) injection of phosphate-buffered saline (PBS) solution, DM + ADSCs group received IC injection of ADSCs, DM + Insulin group received subcutaneous injection of neutral protamine Hagedorn twice a day, and DM + ADSCs + Insulin group received both ADSCs and neutral protamine Hagedorn treatments. Another 10 normal rats were served as control group and received IC injection of PBS. Four weeks after the treatments, intracavernous pressure, histopathological changes in penis, functional proteins of ADSCs, and penis were measured. RESULTS: We found that ADSCs expressed vascular endothelial growth factor, TIMP metallopeptidase inhibitor 1 (TIMP-1), and lipopolysaccharide-inducible CXC chemokine (LIX). ADSC injection partially restored cavernous endothelium and smooth muscle contents and nNOS-positive nerves, and reduced apoptosis in penis compared with PBS-treated diabetic rats. Insulin treatment could further modulate inflammatory response and reduce advanced glycation end-product accumulation in penis. CONCLUSIONS: Better than single therapy, ADSCs combined with insulin ameliorate ED and pathological changes in diabetic rats to near-normal levels. PMID- 26820521 TI - Erratum: Impacts of the ENSO Modoki and other Tropical Indo-Pacific Climate Drivers on African Rainfall. PMID- 26820520 TI - Thermosensitive gemcitabine-magnetoliposomes for combined hyperthermia and chemotherapy. AB - The combination of magnetic hyperthermia therapy with the controlled release of chemotherapeutic agents in tumors may be an efficient therapeutic with few side effects because the bioavailability, tolerance and amount of the drug can be optimized. Here, we prepared magnetoliposomes consisting of magnetite nanoparticle cores and the anticancer drug gemcitabine encapsulated by a phospholipid bilayer. The potential of these magnetoliposomes for controlled drug release and cancer treatment via hyperthermic behavior was investigated. The magnetic nanoparticle encapsulation efficiency was dependent on the initial amount of magnetite nanoparticles present at the encapsulation stage; the best formulation was 66%. We chose this formulation to characterize the physicochemical properties of the magnetoliposomes and to encapsulate gemcitabine. The mean particle size and distribution were determined by dynamic light scattering (DLS), and the zeta potential was measured. The magnetoliposome formulations all had acceptable characteristics for systemic administration, with a mean size of approximately 150 nm and a polydispersity index <0.2. The magnetoliposomes were stable in aqueous suspension for at least one week, as determined by DLS. Temperature increases due to the dissipation energy of magnetoliposome suspensions subjected to an applied alternating magnetic field (AMF) were measured at different magnetic field intensities, and the values were appropriated for cancer treatments. The drug release profile at 37 degrees C showed that 17% of the gemcitabine was released after 72 h. Drug release from magnetoliposomes exposed to an AMF for 5 min reached 70%. PMID- 26820522 TI - Organophosphorus pesticide exposure and neurobehavioral performance in Latino children living in an orchard community. AB - Children living in agricultural communities have a greater risk from pesticides due to para-occupational pathways. The goal of this study was to assess the impact of exposure to organophosphorus pesticides on the neurobehavioral performance of school-aged Latino children over time. Two exposure measures were used to estimate children's pesticide exposure: parent's occupation (agricultural or non-agricultural) and organophosphate residues in home carpet dust samples. During 2008-2011, 206 school-aged children completed a battery of neurobehavioral tests two times, approximately one year apart. The associations between both exposure measures and neurobehavioral performance were examined. Pesticide residues were detected in dust samples from both agricultural and non agricultural homes, however, pesticides were detected more frequently and in higher concentrations in agricultural homes compared to non-agricultural homes. Although few differences were found between agricultural and non-agricultural children at both visits, deficits in learning from the first visit to the second visit, or less improvement, was found in agricultural children relative to non agricultural children. These differences were significant for the Divided Attention and Purdue Pegboard tests. These findings are consistent with previous research showing deficits in motor function. A summary measure of organophosphate residues was not associated with neurobehavioral performance. Results from this study indicate that children in agricultural communities are at increased risk from pesticides as a result of a parent working in agricultural. Our findings suggest that organophosphate exposure may be associated with deficits in learning on neurobehavioral performance, particularly in tests of with motor function. In spite of regulatory phasing out of organophosphates in the U.S., we still see elevated levels and higher detection rates of several organophosphates in agricultural households than non-agricultural households, albeit lower levels than prior studies. PMID- 26820524 TI - Tissue morphodynamics shaping the early mouse embryo. AB - Generation of the elongated vertebrate body plan from the initially radially symmetrical embryo requires comprehensive changes to tissue form. These shape changes are generated by specific underlying cell behaviors, coordinated in time and space. Major principles and also specifics are emerging, from studies in many model systems, of the cell and physical biology of how region-specific cell behaviors produce regional tissue morphogenesis, and how these, in turn, are integrated at the level of the embryo. New technical approaches have made it possible more recently, to examine the morphogenesis of the mouse embryo in depth, and to elucidate the underlying cellular mechanisms. This review focuses on recent advances in understanding the cellular basis for the early fundamental events that establish the basic form of the embryo. PMID- 26820523 TI - Chemotaxis during neural crest migration. AB - Chemotaxis refers to the directional migration of cells towards external, soluble factors along their gradients. It is a process that is used by many different cell types during development for tissue organisation and the formation of embryonic structures, as well as disease like cancer metastasis. The neural crest (NC) is a multipotent, highly migratory cell population that contribute to a range of tissues. It has been hypothesised that NC migration, at least in part, is reliant on chemotactic signals. This review will explore the current evidence for proposed chemoattractants of NC cells, and outline mechanisms for the chemotactic response of the NC to them. PMID- 26820525 TI - A novel long non-coding RNA FGF14-AS2 is correlated with progression and prognosis in breast cancer. AB - Breast cancer is diverse in their natural history and in their responsiveness to treatments. It is urgent to generate candidate biomarkers for the stratification of patients and personalization of therapy to avoid overtreatment or inadequate treatment. Long noncoding RNAs (lncRNAs) have been found to be pervasively transcribed in the genome and played critical roles in cancer progression. A lot of lncRNAs have been reported as potential prognostic biomarkers and therapeutic targets in multiple cancers. In this study, we demonstrated that FGF14 antisense RNA 2 (FGF14-AS2), a novel long non-coding RNA, was significantly down-regulated in breast cancer tissue compared with adjacent normal tissue both in validated cohort and TCGA cohort. Reduced expression of FGF14-AS2 was correlated with larger tumor size, more lymph node metastasis and advanced clinical stage in both cohorts. Kaplan-Meier analysis indicated that patients with lower FGF14-AS2 expression had a worse overall survival. Moreover, multivariate analysis revealed that decreased expression of FGF14-AS2 was an independent predictor of overall survival. Together, these results suggested that FGF14-AS2 involved in the progress of breast cancer and might act as a tumor suppressor gene. To the best of our knowledge, it was firstly reported that FGF14-AS2 was involved in cancer. This study provided a potential new marker and a target for gene therapy in breast cancer treatment. PMID- 26820526 TI - Arabidopsis tRNA ligase completes the cytoplasmic splicing of bZIP60 mRNA in the unfolded protein response. AB - Arabidopsis bZIP60 is a major transcription factor that activates the unfolded protein response and is regulated by cytoplasmic splicing. Two Arabidopsis inositol-requiring 1s (IRE1A and IRE1B) cleave bZIP60 mRNA; however, the ligase that connects the two half-molecules of the split bZIP60 mRNA has not yet been identified. We aimed to determine whether the Arabidopsis tRNA ligase RLG1 catalyzes the ligation of cleaved bZIP60 mRNA. Recombinant IRE1B containing the ribonuclease domain correctly cleaved synthetic RNA covering the cleaved site of bZIP60 in vitro. Recombinant RLG1 then ligated the two cleaved fragments. The cytoplasmic form of RLG1 was expressed in a T-DNA insertion mutant whose homozygote exhibited a lethal phenotype and when the transgene was substituted with endogenous RLG1, the plants grew normally. RLG1 proteins derived from transgene were mainly found in the cytoplasm; however, some were in the microsomal fraction, possibly on the ER membrane. This intracellular distribution of RLG1 is discussed. PMID- 26820527 TI - Role of protein kinase A and class II phosphatidylinositol 3-kinase C2beta in the downregulation of KCa3.1 channel synthesis and membrane surface expression by lyso-globotriaosylceramide. AB - The intermediate conductance calcium-activated potassium channel (KCa3.1) mediates proliferation of many cell types including fibroblasts, and is a molecular target for intervention in various cell proliferative diseases. Our previous study showed that reduction of KCa3.1 channel expression by lyso globotriaosylceramide (lyso-Gb3) inhibits differentiation into myofibroblasts and collagen synthesis, which might lead to development of ascending thoracic aortic aneurysm secondary to Fabry disease. However, how lyso-Gb3 downregulates KCa3.1 channel expression is unknown. Therefore, we aimed to investigate the underlying mechanisms of lyso-Gb3-mediated KCa3.1 channel downregulation, focusing on the cAMP signaling pathway. We found that lyso-Gb3 increased the intracellular cAMP concentration by upregulation of adenylyl cyclase 6 and inhibited ERK 1/2 phosphorylation through the protein kinase A (PKA) pathway, leading to the inhibition of KCa3.1 channel synthesis, not the exchange protein directly activated by cAMP (Epac) pathway. Moreover, lyso-Gb3 suppressed expression of class II phosphatidylinositol 3-kinase C2beta (PI3KC2beta) by PKA activation, which reduces the production of phosphatidylinositol 3-phosphate [PI(3)P], and the reduced membrane surface expression of KCa3.1 channel was recovered by increasing the intracellular levels of PI(3)P. Consequently, our findings that lyso-Gb3 inhibited both KCa3.1 channel synthesis and surface expression by increasing intracellular cAMP, and controlled surface expression through changes in PI3KC2beta-mediated PI(3)P production, suggest that modulation of PKA and PI3KC2beta activity to control of KCa3.1 channel expression can be an alternative important target to attenuate ascending thoracic aortic aneurysms in Fabry disease. PMID- 26820528 TI - Protopanaxatirol type ginsenoside Re promotes cyclic growth of hair follicles via inhibiting transforming growth factor beta signaling cascades. AB - Ginsenosides, the major bio-active ingredients included in Panax ginseng, have been known for the hair growth activity and used to treat patients who suffer from hair loss; however, the detailed mechanisms of this action are still largely unknown. This study was conducted to investigate the molecular and cellular mechanisms responsible for hair growth promoting effect of ginsenoside Re (GRe) in vitro and in vivo. Different doses of minoxidil and GRe were administered topically to the back regions of nude mice for up to 45 days, and hair shaft length and hair cycles were determined for hair promoting activities. Topical treatment of GRe significantly increased the hair shaft length and hair existent time, which was comparable to the action of minoxidil. We also demonstrated that GRe stimulated hair shaft elongation in the ex vivo cultures of vibrissa hair follicles isolated from C57BL/6 mouse. Systemic transcriptome analysis by next generation sequencing demonstrated that TGF-beta-pathway related genes were selectively down-regulated by treatment of GRe in vivo, and the same treatment suppressed TGF-beta-induced phosphorylation of ERK in HeLa cells. The results clearly indicated that GRe is the effective constituent in the ginseng on hair promotion via selective inhibition of the hair growth phase transition related signaling pathways, TGF-beta signaling cascades. PMID- 26820529 TI - Prostaglandin D2 elicits the reversible neurite retraction in hypothalamic cell line. AB - Prostaglandins (PGs) play important roles in diverse physiological processes in the central nervous system. PGD2 is the most abundant PG in the brain and acts through specific receptors, DP1 and CRTH2. We investigated the effects of PGD2 on the morphology of the hypothalamic cell line mHypoE-N37 (N37). In N37 cells, serum starvation induced neurite outgrowth and PGD2 elicited neurite retraction, although we failed to detect transcripts for DP1 and CRTH2. Such an effect of PGD2 was efficiently mimicked by its metabolite, 15-deoxy-Delta(12,14) prostaglandin J2. N-acetyl cysteine completely abolished the effect of PGD2, and reactive oxygen species (ROS) were considered to be important. Notably, neurite outgrowth was restored by PGD2 removal. These results suggest that PGD2 induces reversible neurite retraction in a ROS-mediated mechanism that does not involve any known receptor. PMID- 26820530 TI - SUMOylation regulates nuclear localization and stability of TRAIP/RNF206. AB - TRAIP/RNF206 plays diverse roles in cell cycle progression, DNA damage response, and DNA repair pathways. Physiological importance of TRAIP is highlighted by the identification of pathogenic mutations of TRAIP gene in patients diagnosed with primordial dwarfism. Although the diverse functions of TRAIP in the nucleus have been well characterized, molecular mechanism of TRAIP retention in the nucleus has not been determined. Here, we discovered that TRAIP is post-translationally modified by the small ubiquitin-like protein (SUMO). In addition, we identified five SUMOylation sites in TRAIP, and successfully generated SUMOylation deficient mutant of TRAIP. In an attempt to define the functional roles of TRAIP SUMOylation, we discovered that SUMOylation deficient TRAIP is not retained in the nucleus. In addition, protein stability of SUMOylation deficient TRAIP is lower than wild type TRAIP, demonstrating that SUMOylation is critical for both proper subcellular localization and protein stability of TRAIP. Taken together, these findings improve the understanding clinical implication of TRAIP in various diseases including primordial dwarfism and cancers. PMID- 26820531 TI - Meta-analysis method for discovering reliable biomarkers by integrating statistical and biological approaches: An application to liver toxicity. AB - Biomarkers that are identified from a single study often appear to be biologically irrelevant or false positives. Meta-analysis techniques allow integrating data from multiple studies that are related but independent in order to identify biomarkers across multiple conditions. However, existing biomarker meta-analysis methods tend to be sensitive to the dataset being analyzed. Here, we propose a meta-analysis method, iMeta, which integrates t-statistic and fold change ratio for improved robustness. For evaluation of predictive performance of the biomarkers identified by iMeta, we compare our method with other meta analysis methods. As a result, iMeta outperforms the other methods in terms of sensitivity and specificity, and especially shows robustness to study variance increase; it consistently shows higher classification accuracy on diverse datasets, while the performance of the others is highly affected by the dataset being analyzed. Application of iMeta to 59 drug-induced liver injury studies identified three key biomarker genes: Zwint, Abcc3, and Ppp1r3b. Experimental evaluation using RT-PCR and qRT-PCR shows that their expressional changes in response to drug toxicity are concordant with the result of our method. iMeta is available at http://imeta.kaist.ac.kr/index.html. PMID- 26820532 TI - Rho GTPase protein Cdc42 is critical for postnatal cartilage development. AB - Cdc42, a small Rho GTPase family member, has been shown to regulate multiple cellular functions in vitro, including actin cytoskeletal reorganization, cell migration, proliferation, and gene expression. However, its tissue-specific roles in vivo remain largely unknown, especially in postnatal cartilage development, as cartilage-specific Cdc42 inactivated mice die within a few days after birth. In this study, we investigated the physiological functions of Cdc42 during cartilage development after birth using tamoxifen-induced cartilage-specific inactivated Cdc42 conditional knockout (Cdc42 (fl/fl); Col2-CreERT) mice, which were generated by crossing Cdc42 flox mice (Cdc42 (fl/fl)) with tamoxifen-induced type II collagen (Col2) Cre transgenic mice using a Cre/loxP system. The gross morphology of the Cdc42 cKO mice was shorter limbs and body, as well as reduced body weight as compared with the controls. In addition, severe defects were found in growth plate chondrocytes of the long bones, characterized by a shorter proliferating zone (PZ), wider hypertrophic zone (HZ), and loss of columnar organization of proliferating chondrocytes, resulting in delayed endochondral bone formation associated with abnormal bone growth. Our findings demonstrate the importance of Cdc42 for cartilage development during both embryonic and postnatal stages. PMID- 26820533 TI - Inhibitory effects of two G protein-coupled receptor kinases on the cell surface expression and signaling of the human adrenomedullin receptor. AB - Receptor activity-modifying protein 2 (RAMP2) enables the calcitonin receptor like receptor (CLR, a family B GPCR) to form the type 1 adrenomedullin receptor (AM1 receptor). Here, we investigated the effects of the five non-visual GPCR kinases (GRKs 2 through 6) on the cell surface expression of the human (h)AM1 receptor by cotransfecting each of these GRKs into HEK-293 cells that stably expressed hRAMP2. Flow cytometric analysis revealed that when coexpressed with GRK4 or GRK5, the cell surface expression of the AM1 receptor was markedly decreased prior to stimulation with AM, thereby attenuating both the specific [(125)I]AM binding and AM-induced cAMP production. These inhibitory effects of both GRKs were abolished by the replacement of the cytoplasmic C-terminal tail (C tail) of CLR with that of the calcitonin receptor (a family B GPCR) or beta2 adrenergic receptor (a family A GPCR). Among the sequentially truncated CLR C tail mutants, those lacking the five residues 449-453 (Ser-Phe-Ser-Asn-Ser) abolished the inhibition of the cell surface expression of CLR via the overexpression of GRK4 or GRK5. Thus, we provided new insight into the function of GRKs in agonist-unstimulated GPCR trafficking using a recombinant AM1 receptor and further determined the region of the CLR C-tail responsible for this GRK function. PMID- 26820534 TI - Crystal structure of hGEF-H1 PH domain provides insight into incapability in phosphoinositide binding. AB - The guanine nucleotide exchange factor GEF-H1 (also known as ARHGEF2) is identified as a member of the Dbl family of GEFs. It regulates RhoA-dependent cell signaling pathways and plays important roles in biological processes. GEF-H1 contains an N-terminal zinc finger domain, a Dbl-homologous (DH) domain followed by a Pleckstrin homology (PH) domain, and a C-terminal domain. The specific roles of its PH domain are poorly understood. Here we report the crystal structure of human GEF-H1 PH domain to 2.45 A resolution. A conserved surface is formed by beta8, beta9, beta10, and it may mediate protein-protein interactions. Although the folding resembles other PH domains that have defined structures, superposition of different PH domains clearly shows that the loop between beta6/beta7 and the loop between beta3/beta4 are so close that they will prevent its binding with phosphoinositide due to steric hindrance, and this has been proved by isothermal titration calorimetry (ITC) and thermal shift assay (TSA). Our studies provide a structural framework for further work on the function of GEF-H1. PMID- 26820535 TI - 5-Aminolevulinic acid combined with ferrous iron ameliorate ischemia-reperfusion injury in the mouse fatty liver model. AB - BACKGROUND: The fatty liver could increase the risk of serious acute ischemia reperfusion (I/R) injury, and hepatic steatosis is indeed a major risk factor for hepatic failure after grafting a fatty liver. MATERIALS & METHODS: Fatty liver models of methionine- and choline-deficient high-fat mice were subjected to I/R injury with or without 5-aminolevulinic acid (5-ALA)/sodium ferrous citrate (SFC) treatment. Levels of hepatic enzymes, lipid peroxidation and apoptosis, inflammatory cytokines and heme oxygenase (HO)-1, and the carbon monoxide (CO) in the liver, and reactive oxygen species (ROS), inflammatory cytokines and members of the signaling pathway in isolated Kupffer were assessed. RESULTS: Alanine aminotransferase and aspartate aminotransferase levels, the number of necrotic areas, thiobarbituric acid reactive substance content, TUNEL-positive cells, infiltrated macrophages, and the inflammatory cytokine expression after I/R injury were dramatically decreased, whereas the endogenous CO concentrations and the HO-1 expression were significantly increased by 5-ALA/SFC treatment. The expression of toll-like receptors 2 and 4, NF-kappaB and inflammatory cytokines and ROS production in Kupffer cells were significantly decreased with 5-ALA/SFC treatment. CONCLUSION: 5-ALA/SFC significantly attenuates the injury level in the fatty liver after I/R injury. PMID- 26820536 TI - ANKRD53 interacts with DDA3 and regulates chromosome integrity during mitosis. AB - Spindle dynamics drives chromosome movement and mitotic progression during mitosis. Microtubule (MT)-associated proteins (MAPs) regulate MT stabilization/destabilization and MT polymerization/depolymerization for congression of sister chromatids at the mitotic equator and subsequent segregation toward the spindle poles. Here, we identified ANKRD53 as a novel DDA3 interacting protein through proteomic analysis. Based on expression profiles, ANKRD53 is phosphorylated by mitotic kinases during mitosis. In ANKRD53-depleted HeLa cells, the progression of mitosis was delayed and the number of unaligned chromosomes increased substantially. In addition, spindle MT polymerization decreased and the spindle assembly checkpoint (SAC) was concomitantly activated by the decreased spindle dynamics in ANKRD53-depleted cells. Although ANKRD53 is recruited to the mitotic spindle by DDA3, it counteracts the activity of DDA3 for spindle MT polymerization. Furthermore, ANKRD53 depletion increased the number of bi-nuclei and polylobed nuclei. Thus, ANKRD53 is recruited to the mitotic spindle by DDA3 and acts as a regulator of spindle dynamics and cytokinesis. PMID- 26820537 TI - Tracking protein-protein interaction and localization in living cells using a high-affinity molecular binder. AB - Probing protein-protein interactions in living cells is crucial for understanding the protein functions and developing drugs. Small-sized protein binders are considered effective and useful for such analysis. Here we describe the development and use of a repebody, which is a protein binder composed of LRR (Leucine-rich repeat) modules, for tracking protein-protein interaction and localization in real-time through live-cell imaging. A repebody with high affinity for a red fluorescent protein was selected through a phage display, fused with a green fluorescent protein, and applied for tracing a red fluorescent protein-fused target protein in mammalian cells. The potential and utility of our approach was demonstrated by tracking the rapamycin-mediated interaction between FKBP12-rapamycin binding (FRB) domain and a FK506-binding protein (FKBP) and their localization by live-cell imaging. The present approach can be widely used for the analysis of protein-protein interaction and an understanding of complex biological processes in living cells. PMID- 26820538 TI - Transdifferentiation of mouse visceral yolk sac cells into parietal yolk sac cells in vitro. AB - The mouse embryonic yolk sac is an extraembryonic membrane that consists of a visceral yolk sac (VYS) and parietal yolk sac (PYS), and functions in hematopoietic-circulation in the fetal stage. The present study was undertaken to examine the normal development of both murine VYS and PYS tissues using various molecular markers, and to establish a novel VYS cell culture system in vitro for analyzing differentiation potentials of VYS cells. RT-PCR and immunohistochemical analyses of gene expression in VYS and PYS tissues during development revealed several useful markers for their identification: HNF1beta, HNF4alpha, Cdh1 (E cadherin), Krt8 and Krt18 for VYS epithelial cells, and Stra6, Snail1, Thbd and vimentin for PYS cells. PYS cells exhibited mesenchymal characteristics in gene expression and morphology. When VYS cells at 11.5 days of gestation were cultured in vitro for 7 days, the number of HNF1beta-, HNF4alpha-, E-cadherin- and cytokeratin-positive VYS epithelial cells was significantly reduced and, instead, Stra6-and vimentin-positive PYS-like cells increased with culture. RT-PCR analyses also demonstrated that gene expression of VYS markers decreased, whereas that of PYS markers increased in the primary culture of VYS cells. These data indicate that VYS epithelial cells rapidly transdifferentiate into PYS cells having mesenchymal characteristics in vitro, which may provide a culture system suitable for studying molecular mechanisms of VYS transdifferentiation into PYS cells and also epithelial-mesenchymal transition. PMID- 26820539 TI - Periostin promotes secretion of fibronectin from the endoplasmic reticulum. AB - Extracellular matrix (ECM) proteins are synthesized in the endoplasmic reticulum (ER), transported to the extracellular milieu through the secretory pathway, and assembled into an extracellular architecture. A previous study of ours showed that periostin, a secretory protein, interacts with fibronectin and is involved in ECM remodeling. Here we show that periostin played a role in fibronectin secretion from the ER. Co-immunoprecipitation and in situ proximity ligation assays revealed an interaction between periostin and fibronectin in the ER. Although accumulation of fibronectin was detected in the ER of fibroblastic C3H10T1/2 cells, forced expression of periostin in those cells decreased the accumulation of fibronectin in the ER, suggesting that periostin promoted the secretion of fibronectin. A substitution mutant of tryptophan at the position 65 to alanine in the EMI domain of periostin, which caused periostin to lose its ability to interact with fibronectin, did not decrease the accumulation. Furthermore, targeted disruption of periostin in mice caused the non-fibrillar and ectopic deposition of fibronectin in the periodontal ligament. Thus, these results demonstrate a subcellular role of periostin in promotion of fibronectin secretion from the ER. PMID- 26820540 TI - Solutions for quantifying P-value uncertainty and replication power. PMID- 26820541 TI - Response to Lazzeroni et al. PMID- 26820542 TI - Estimation statistics should replace significance testing. PMID- 26820543 TI - The mutation significance cutoff: gene-level thresholds for variant predictions. PMID- 26820544 TI - Genetics: profiling DNA methylation and beyond. PMID- 26820545 TI - Illuminating translation with ribosome profiling spectra. PMID- 26820546 TI - Hidden in the mist no more: physical force in cell biology. PMID- 26820548 TI - Time-Lag in Responses of Birds to Atlantic Forest Fragmentation: Restoration Opportunity and Urgency. AB - There are few opportunities to evaluate the relative importance of landscape structure and dynamics upon biodiversity, especially in highly fragmented tropical landscapes. Conservation strategies and species risk evaluations often rely exclusively on current aspects of landscape structure, although such limited assumptions are known to be misleading when time-lag responses occur. By relating bird functional-group richness to forest patch size and isolation in ten-year intervals (1956, 1965, 1978, 1984, 1993 and 2003), we revealed that birds with different sensitivity to fragmentation display contrasting responses to landscape dynamics in the Brazilian Atlantic Forest. For non-sensitive groups, there was no time-lag in response: the recent degree of isolation best explains their variation in richness, which likely relates to these species' flexibility to adapt to changes in landscape structure. However, for sensitive bird groups, the 1978 patch area was the best explanatory variable, providing evidence for a 25 year time-lag in response to habitat reduction. Time-lag was more likely in landscapes that encompass large patches, which can support temporarily the presence of some sensitive species, even when habitat cover is relatively low. These landscapes potentially support the most threatened populations and should be priorities for restoration efforts to avoid further species loss. Although time-lags provide an opportunity to counteract the negative consequences of fragmentation, it also reinforces the urgency of restoration actions. Fragmented landscapes will be depleted of biodiversity if landscape structure is only maintained, and not improved. The urgency of restoration action may be even higher in landscapes where habitat loss and fragmentation history is older and where no large fragment remained to act temporarily as a refuge. PMID- 26820549 TI - Free variable selection QSPR study to predict (19)F chemical shifts of some fluorinated organic compounds using Random Forest and RBF-PLS methods. AB - In this work, two new and powerful chemometrics methods are applied for the modeling and prediction of the (19)F chemical shift values of some fluorinated organic compounds. The radial basis function-partial least square (RBF-PLS) and random forest (RF) are employed to construct the models to predict the (19)F chemical shifts. In this study, we didn't used from any variable selection method and RF method can be used as variable selection and modeling technique. Effects of the important parameters affecting the ability of the RF prediction power such as the number of trees (nt) and the number of randomly selected variables to split each node (m) were investigated. The root-mean-square errors of prediction (RMSEP) for the training set and the prediction set for the RBF-PLS and RF models were 44.70, 23.86, 29.77, and 23.69, respectively. Also, the correlation coefficients of the prediction set for the RBF-PLS and RF models were 0.8684 and 0.9313, respectively. The results obtained reveal that the RF model can be used as a powerful chemometrics tool for the quantitative structure-property relationship (QSPR) studies. PMID- 26820550 TI - Urgency Incontinence before and after Revision of a Synthetic Mid Urethral Sling. AB - PURPOSE: We evaluate urgency urinary incontinence outcomes for patients who underwent revision of a presumed obstructing synthetic mid urethral sling and examine risk factors for persistent or de novo symptoms after surgery. MATERIALS AND METHODS: From February 1, 2005 to June 1, 2013, 107 women underwent sling revision for new or worsening lower urinary tract symptoms after synthetic mid urethral sling surgery. Patients were grouped based on urgency urinary incontinence symptoms and characteristics associated with persistent or de novo symptoms after revision were examined using logistic regression models. RESULTS: Median followup was 29 months (IQR 12-54) and time to revision was 21 months (IQR 5-48). Patients presenting for sling revision with urgency incontinence (68) were more likely to experience a more than 6-month delay to revision vs those presenting with obstructive voiding symptoms (39) (OR 3.25, 95% CI 1.33-7.92, p <0.01). After revision urgency incontinence persisted in 76.5% (52 of 68) and was associated with a pre-revision need for anticholinergic medication (OR 5.58, 95% CI 1.44-21.39, p=0.01) and smoking (OR 5.21, 95% CI 1.21-22.49, p=0.03). De novo urgency incontinence developed in 43.6% (17 of 39) of patients and was associated with de novo stress incontinence (OR 15.9, 95% CI 3.2-78.3, p <0.01). Women with post-revision urgency incontinence (de novo or persistent) had higher Urogenital Distress Inventory-6 scores than patients with no or resolution of urgency incontinence. CONCLUSIONS: Patients presenting with new or worsening urgency urinary incontinence after sling placement were more likely to undergo delayed revision compared to those presenting with obstructive voiding symptoms. There is a high rate of bothersome persistent and de novo urgency incontinence after sling revision. Patient expectations should be managed accordingly before sling revision. PMID- 26820547 TI - Editing the epigenome: technologies for programmable transcription and epigenetic modulation. AB - Gene regulation is a complex and tightly controlled process that defines cell identity, health and disease, and response to pharmacologic and environmental signals. Recently developed DNA-targeting platforms, including zinc finger proteins, transcription activator-like effectors (TALEs) and the clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 system, have enabled the recruitment of transcriptional modulators and epigenome-modifying factors to any genomic site, leading to new insights into the function of epigenetic marks in gene expression. Additionally, custom transcriptional and epigenetic regulation is facilitating refined control over cell function and decision making. The unique properties of the CRISPR-Cas9 system have created new opportunities for high-throughput genetic screens and multiplexing targets to manipulate complex gene expression patterns. This Review summarizes recent technological developments in this area and their application to biomedical challenges. We also discuss remaining limitations and necessary future directions for this field. PMID- 26820551 TI - Augmented Reality Using Transurethral Ultrasound for Laparoscopic Radical Prostatectomy: Preclinical Evaluation. AB - PURPOSE: To guide the surgeon during laparoscopic or robot-assisted radical prostatectomy an innovative laparoscopic/ultrasound fusion platform was developed using a motorized 3-dimensional transurethral ultrasound probe. We present what is to our knowledge the first preclinical evaluation of 3-dimensional prostate visualization using transurethral ultrasound and the preliminary results of this new augmented reality. MATERIALS AND METHODS: The transurethral probe and laparoscopic/ultrasound registration were tested on realistic prostate phantoms made of standard polyvinyl chloride. The quality of transurethral ultrasound images and the detection of passive markers placed on the prostate surface were evaluated on 2-dimensional dynamic views and 3-dimensional reconstructions. The feasibility, precision and reproducibility of laparoscopic/transurethral ultrasound registration was then determined using 4, 5, 6 and 7 markers to assess the optimal amount needed. The root mean square error was calculated for each registration and the median root mean square error and IQR were calculated according to the number of markers. RESULTS: The transurethral ultrasound probe was easy to manipulate and the prostatic capsule was well visualized in 2 and 3 dimensions. Passive markers could precisely be localized in the volume. Laparoscopic/transurethral ultrasound registration procedures were performed on 74 phantoms of various sizes and shapes. All were successful. The median root mean square error of 1.1 mm (IQR 0.8-1.4) was significantly associated with the number of landmarks (p = 0.001). The highest accuracy was achieved using 6 markers. However, prostate volume did not affect registration precision. CONCLUSIONS: Transurethral ultrasound provided high quality prostate reconstruction and easy marker detection. Laparoscopic/ultrasound registration was successful with acceptable mm precision. Further investigations are necessary to achieve sub mm accuracy and assess feasibility in a human model. PMID- 26820552 TI - A Mathematical Method to Calculate Tumor Contact Surface Area: An Effective Parameter to Predict Renal Function after Partial Nephrectomy. AB - PURPOSE: We proposed a mathematical formula to calculate contact surface area between a tumor and renal parenchyma. We examined the applicability of using contact surface area to predict renal function after partial nephrectomy. MATERIALS AND METHODS: We performed this retrospective study in patients who underwent partial nephrectomy between January 2012 and December 2014. Based on abdominopelvic computerized tomography or magnetic resonance imaging, we calculated the contact surface area using the formula (2*pi*radius*depth) developed by integral calculus. We then evaluated the correlation between contact surface area and perioperative parameters, and compared contact surface area and R.E.N.A.L. (Radius/Exophytic/endophytic/Nearness to collecting system/Anterior/Location) score in predicting a reduction in renal function. RESULTS: Overall 35, 26 and 45 patients underwent partial nephrectomy with open, laparoscopic and robotic approaches, respectively. Mean +/- SD contact surface area was 30.7+/-26.1 cm(2) and median (IQR) R.E.N.A.L. score was 7 (2.25). Spearman correlation analysis showed that contact surface area was significantly associated with estimated blood loss (p=0.04), operative time (p=0.04) and percent change in estimated glomerular filtration rate (p <0.001). On multivariate analysis contact surface area and R.E.N.A.L. score independently affected percent change in estimated glomerular filtration rate (p <0.001 and p=0.03, respectively). On ROC curve analysis contact surface area was a better independent predictor of a greater than 10% change in estimated glomerular filtration rate compared to R.E.N.A.L. score (AUC 0.86 vs 0.69). CONCLUSIONS: Using this simple mathematical method, contact surface area was associated with surgical outcomes. Compared to R.E.N.A.L. score, contact surface area was a better predictor of functional change after partial nephrectomy. PMID- 26820553 TI - Synthesis and structure-activity relationship studies of novel 3,9-substituted alpha-carboline derivatives with high cytotoxic activity against colorectal cancer cells. AB - In our continued focus on 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) analogs, we synthesized a novel series of 3,9-substituted alpha-carboline derivatives and evaluated the new compounds for antiproliferactive effects. Structure activity relationships revealed that a COOCH3 or CH2OH group at position-3 and substituted benzyl group at position-9 of the alpha-carboline nucleus were crucial for maximal activity. The most active compound, 11, showed high levels of cytotoxicity against HL-60, COLO 205, Hep 3B, and H460 cells with IC50 values of 0.3, 0.49, 0.7, and 0.8 MUM, respectively. The effect of compound 11 on the cell cycle distribution demonstrated G2/M arrest in COLO 205 cells. Furthermore, mechanistic studies indicated that compound 11 induced apoptosis by activating death receptor and mitochondria dependent apoptotic signaling pathways in COLO 205 cells. The new 3,9-substituted alpha-carboline derivatives exhibited excellent anti-proliferative activities, and compound 11 can be used as a promising pro-apoptotic agent for future development of new antitumor agents. PMID- 26820555 TI - Synthesis and evaluation of colletoic acid core derivatives. AB - Cortisol homeostasis has been linked to the pathogenesis of metabolic syndrome (MetS), since it stimulates hepatic gluconeogenesis and adipogenesis. MetS is classified as a constellation of health conditions that increase the risk of type 2 diabetes and cardiovascular disease. Intracellular cortisol levels are regulated by 11beta-hydroxysteroid dehydrogenase (type 1 and type 2) in a tissue dependent manner. The type 1 enzyme (11beta-HSD1) is widely expressed in glucocorticoid targeted tissues and is responsible for the conversion of cortisone to the active cortisol. Local reduction of cortisol regeneration presents a potential strategy for MetS treatment. Recently we disclosed the total synthesis of (+)-colletoic acid as a potent 11beta-HSD1 inhibitor. Herein, we describe our improved processing chemistry for the synthesis of the colletoic acid core to access a diverse number of derivatives for evaluation against 11beta HSD1. The Evan's chiral auxiliary was utilized to construct the acyclic precursor 12 to afford the acorane core 9 using a modified Heck reaction in excellent chemical yields. The colletoic acid core derivatives showed modest activity against 11beta-HSD1 and will serve for further biological evaluation. PMID- 26820554 TI - Discovery of novel 4-(2-pyrimidinylamino)benzamide derivatives as highly potent and orally available hedgehog signaling pathway inhibitors. AB - A series of novel hedgehog signaling pathway inhibitors have been designed by structural modification based on the former reported scaffold of 4-(2 pyrimidinylamino)benzamide. The SAR for this series was described and many derivatives showed potent inhibitory activity. Among these compounds, compounds 12af and 12bf were identified to have high potency and optimal PK profiles. Although both of compounds 12af and 12bf did not show strong antitumor efficacy in LS-174T nude mice model, they were promising candidates as Hh signaling inhibitors due to great potency against Hh signaling pathway and outstanding PK properties, deserving further evaluation in other Hh signaling operative tumor models. PMID- 26820556 TI - Synthesis, in vitro and in vivo pharmacological evaluation of serotoninergic ligands containing an isonicotinic nucleus. AB - Isonicotinamide derivatives, linked to an arylpiperazine moiety, were prepared and their affinity to 5-HT1A, 5-HT2A and 5-HT2C receptors were evaluated. The combination of structural elements (heterocyclic nucleus, alkyl chain and 4 substituted piperazine) known to play critical roles in affinity for serotoninergic receptors and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. In binding studies, several molecules showed high affinity in nanomolar and subnanomolar range at 5-HT1A, 5-HT2A and 5-HT2C receptors and moderate or no affinity for other relevant receptors (D1, D2, alpha1 and alpha2). N-(3-(4-(bis(4 fluorophenyl)methyl)piperazin-1-yl)propyl)isonicotinamide (4s) with Ki = 0.130 nM, was the most active and selective derivative for the 5-HT1A receptor compared to other serotoninergic, dopaminergic and adrenergic receptors. Compound 4o, instead, showed 5-HT2A affinity values in subnamolar range. Moreover, the compounds having better affinity and selectivity binding profile towards 5-HT1A and 5-HT2A receptors were selected in order to be tested by in vitro and in vivo assays to determine their functional activity. PMID- 26820557 TI - Beta-blockers for congestive heart failure in children. AB - BACKGROUND: Beta-blockers are an essential part of standard therapy in adult congestive heart failure and therefore, are expected to be beneficial in children. However, congestive heart failure in children differs from that in adults in terms of characteristics, aetiology, and drug clearance. Therefore, paediatric needs must be specifically investigated. This is an update of a Cochrane review previously published in 2009. OBJECTIVES: To assess the effect of beta-adrenoceptor-blockers (beta-blockers) in children with congestive heart failure. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS up to November 2015. Bibliographies of identified studies were checked. No language restrictions were applied. SELECTION CRITERIA: Randomised, controlled, clinical trials investigating the effect of beta-blocker therapy on paediatric congestive heart failure. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and assessed data from the included trials. MAIN RESULTS: We identified four new studies for the review update; the review now includes seven studies with 420 participants. Four small studies with 20 to 30 children each, and two larger studies of 80 children each, showed an improvement of congestive heart failure with beta-blocker therapy. A larger study with 161 participants showed no evidence of benefit over placebo in a composite measure of heart failure outcomes. The included studies showed no significant difference in mortality or heart transplantation rates between the beta-blocker and control groups. No significant adverse events were reported with beta-blockers, apart from one episode of complete heart block. A meta-analysis of left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) data showed a very small improvement with beta-blockers.However, there were vast differences in the age, age range, and health of the participants (aetiology and severity of heart failure; heterogeneity of diagnoses and co-morbidities); there was a range of treatments across studies (choice of beta-blocker, dosing, duration of treatment); and a lack of standardised methods and outcome measures. Therefore, the primary outcomes could not be pooled in meta-analyses. AUTHORS' CONCLUSIONS: There is not enough evidence to support or discourage the use of beta-blockers in children with congestive heart failure, or to propose a paediatric dosing scheme. However, the sparse data available suggested that children with congestive heart failure might benefit from beta-blocker treatment. Further investigations in clearly defined populations with standardised methodology are required to establish guidelines for therapy. Pharmacokinetic investigations of beta-blockers in children are also required to provide effective dosing in future trials. PMID- 26820558 TI - 'Goats that stare at men'--revisited: do dwarf goats alter their behaviour in response to eye visibility and head direction of a human? AB - Being able to recognise when one is being observed by someone else is thought to be adaptive during cooperative or competitive events. In particular for prey species, this ability should be of use in the context of predation. A previous study reported that goats (Capra aegagrus hircus) alter their behaviour according to the body and head orientation of a human experimenter. During a food anticipation task, an experimenter remained in a particular posture for 30 s before delivering a reward, and the goats' active anticipation and standing alert behaviour were analysed. To further evaluate the specific mechanisms at work, we here present two additional test conditions. In particular, we investigated the effects of the eye visibility and head orientation of a human experimenter on the behaviour of the goats (N = 7). We found that the level of the subjects' active anticipatory behaviour was highest in the conditions where the experimenter was directing his head and body towards the goat ('Control' and 'Eyes closed' conditions), but the anticipatory behaviour was significantly decreased when the body ('Head only') or the head and body of the experimenter were directed away from the subject ('Back' condition). For standing alert, we found no significant differences between the three conditions in which the experimenter was directing his head towards the subject ('Control', 'Eyes closed' and 'Head only'). This lack of differences in the expression of standing alert suggests that goats evaluate the direction of a human's head as an important cue in their anticipatory behaviour. However, goats did not respond to the visibility of the experimenter's eyes alone. PMID- 26820559 TI - Compliance with prospective trial registration guidance remained low in high impact journals and has implications for primary end point reporting. AB - OBJECTIVES: To examine compliance with International Committee of Medical Journal Editors' (ICMJE) policy on prospective trial registration along with predictors of compliance. STUDY DESIGN AND SETTING: Cross-sectional analysis of all articles reporting trial results published in the six highest-impact general medicine journals in January-June 2014 that were registered in a public trial registry. The main outcome measure was compliance with ICMJE policy. The time frame for trial primary end point ascertainment was used to assess whether retrospective registration could have allowed changing of primary end points following an interim analysis. RESULTS: Forty of 144 (28%) articles did not comply with the ICMJE policy. Trials of non-FDA-regulated interventions were less compliant than trials of FDA-regulated interventions (i.e., medicines, medical devices) (42% vs. 21%; P = 0.016). Twenty-nine of these 40 (72%; 20% overall) were registered before any interim analysis of primary end points could have been conducted; 11 (28%; 8% overall) were registered after primary end point ascertainment, such that investigators could have had the opportunity to conduct an interim analysis before trial registration. CONCLUSION: Twenty-eight percent of trials published in high-impact journals were retrospectively registered including nearly 10% that were registered after primary end point ascertainment could have had taken place. Prospective registration should be prompted and enforced to ensure transparency and accountability in clinical research. PMID- 26820560 TI - Role of Cardiac CT Before Transcatheter Aortic Valve Implantation (TAVI). AB - Catheter-based aortic valve implantation is increasingly being performed in high risk patients with symptomatic aortic valve stenosis. For successful planning of the procedure, CT has been shown to provide crucial information concerning the aortic root as well as the peripheral access vessels. This article illustrates the increasing role of CT before transcatheter aortic valve implantation. PMID- 26820561 TI - Temperature and pH dependence of DNA ejection from archaeal lemon-shaped virus His1. AB - The archaeal virus His1 isolated from a hypersaline environment infects an extremely halophilic archaeon Haloarcula hispanica. His1 features a lemon-shaped capsid, which is so far found only in archaeal viruses. This unique capsid can withstand high salt concentrations, and can transform into a helical tube, which in turn is resistant to extremely harsh conditions. Hypersaline environments exhibit a wide range of temperatures and pH conditions, which present an extra challenge to their inhabitants. We investigated the influence of pH and temperature on DNA ejection from His1 virus using single-molecule fluorescence experiments. The observed number of ejecting viruses is constant in pH 5 to 9, while the ejection process is suppressed at pH below 5. Similarly, the number of ejections within 15-42 degrees C shows only a minor increase around 25-37 degrees C. The maximum velocity of single ejected DNA increases with temperature, in qualitative agreement with the continuum model of dsDNA ejection. PMID- 26820563 TI - Metanephrine neuroendocrine tumor marker detection by SERS using Au nanoparticle/Au film sandwich architecture. AB - Neuroendocrine tumors, such as pheochromocytoma or paraganglioma, are dangerous tumors that constitute a potential threat for a large number of patients. Currently, the biochemical diagnosis of neuroendocrine tumors is based on measurement of the direct secretory products of the adrenomedullary-sympathetic system or of their metabolites, such as catecholamines or their metanephrine derivatives, from plasma or urine. The techniques used for analysis of plasma free metanephrines, i.e. high-performance liquid chromatography or high performance liquid chromatography coupled with mass-spectrometry are technically demanding and time consuming, which limit their availability. Here we demonstrate a simple, fast and low-cost method for detecting metanephrine by Surface Enhanced Raman Scattering (SERS). The protocol consists in using evaporation-induced self assembly of gold (Au) nanoparticles incubated with the analyte, on planar gold films. The assembly process produces regions with a dense distribution of both inter-particle gaps and particle-film gaps. Finite-difference time-domain simulations confirm that both kinds of gaps are locations of enhanced electromagnetic fields resulting from inter-particle and particle-film plasmonic coupling, useful for SERS amplification. Metanephrine vibrational bands assignment was performed according to density functional theory calculations. Metanephrine metabolite was detected in liquid at concentration levels lower than previously reported for other similar metabolites. The obtained results demonstrate that the Au nanoparticle/Au film exhibits noticeable SERS amplification of the adsorbed metabolite and can be used in the design of efficient, stable SERS-active substrates for the detection and identification of specific tumor markers. PMID- 26820562 TI - Binding of phenothiazines into allosteric hydrophobic pocket of human thioredoxin 1. AB - Thioredoxins are multifunctional oxidoreductase proteins implicated in the antioxidant cellular apparatus and oxidative stress. They are involved in several pathologies and are promising anticancer targets. Identification of noncatalytic binding sites is of great interest for designing new allosteric inhibitors of thioredoxin. In a recent work, we predicted normal mode motions of human thioredoxin 1 and identified two major putative hydrophobic binding sites. In this work we investigated noncovalent interactions of human thioredoxin 1 with three phenotiazinic drugs acting as prooxidant compounds by using molecular docking and circular dichroism spectrometry to probe ligand binding into the previously predicted allosteric hydrophobic pockets. Our in silico and CD spectrometry experiments suggested one preferred allosteric binding site involving helix 3 and adopting the best druggable conformation identified by NMA. The CD spectra showed binding of thioridazine into thioredoxin 1 and suggested partial helix unfolding, which most probably concerns helix 3. Taken together, these data support the strategy to design thioredoxin inhibitors targeting a druggable allosteric binding site. PMID- 26820565 TI - Individual species affect plant traits structure in their surroundings: evidence of functional mechanisms of assembly. AB - Evaluating community assembly through the use of functional traits is a promising tool for testing predictions arising from Niche and Coexistence theories. Although interactions among neighboring species and their inter-specific differences are known drivers of coexistence with a strong spatial signal, assessing the role of individual species on the functional structure of the community at different spatial scales remains a challenge. Here, we ask whether individual species exert a measurable effect on the spatial organization of different functional traits in local assemblages. We first propose and compute two functions that describe different aspects of functional trait organization around individual species at multiple scales: individual weighted mean area relationship and individual functional diversity area relationship. Secondly, we develop a conceptual model on the relationship and simultaneous variation of these two metrics, providing five alternative scenarios in response to the ability of some target species to modify its neighbor environment and the possible assembly mechanisms involved. Our results show that some species influence the spatial structure of specific functional traits, but their effects were always restricted to the finest spatial scales. In the basis of our conceptual model, the observed patterns point to two main mechanisms driving the functional structure of the community at the fine scale, "biotic" filtering meditated by individual species and resource partitioning driven by indirect facilitation rather than by competitive mechanisms. PMID- 26820566 TI - Consequences of exotic host use: impacts on Lepidoptera and a test of the ecological trap hypothesis. AB - Investigating the effects of invasive species on native biodiversity is one of the most pressing challenges in ecology. Our goal in this study was to quantify the effects of invasive plants on butterfly and moth communities. In addition, we sought to elucidate the fitness consequences of non-native hosts on lepidopterans. We conducted a meta-analysis on a total of 76 studies which provided data on larval performance, survival, oviposition preference, abundance, and species richness of Lepidoptera on native and exotic plants. Overwhelmingly, we found that performance and survival were reduced for larvae developing on exotic hosts, relative to native hosts. At the community level, alien plant invasion was associated with a reduction in the overall abundance and richness of lepidopteran communities. We found that lepidopterans did not show strong oviposition preference for native hosts. This result suggests that many invasive plant species may decrease lepidopteran abundance by providing a target for oviposition where larvae have a relatively poor chance of survival. Among studies that tested both survival and preference on exotic hosts, 37.5 % found evidence for novel hosts that could function as ecological traps (the figure was 18 % when considering studies that only assayed larval performance). Thus, although the majority of novel hosts included in our analyses are not likely to act as ecological traps, the potential clearly exists for this effect, and the role of ecological traps should be considered along with other aspects of global change impacting natural communities. PMID- 26820567 TI - Direction of interaction between mountain pine beetle (Dendroctonus ponderosae) and resource-sharing wood-boring beetles depends on plant parasite infection. AB - Plant pathogens can have cascading consequences on insect herbivores, though whether they alter competition among resource-sharing insect herbivores is unknown. We experimentally tested whether the infection of a plant pathogen, the parasitic plant dwarf mistletoe (Arceuthobium americanum), on jack pine (Pinus banksiana) altered the competitive interactions among two groups of beetles sharing the same resources: wood-boring beetles (Coleoptera: Cerambycidae) and the invasive mountain pine beetle (Dendroctonus ponderosae) (Coleoptera: Curculionidae). We were particularly interested in identifying potential mechanisms governing the direction of interactions (from competition to facilitation) between the two beetle groups. At the lowest and highest disease severity, wood-boring beetles increased their consumption rate relative to feeding levels at moderate severity. The performance (brood production and feeding) of mountain pine beetle was negatively associated with wood-boring beetle feeding and disease severity when they were reared separately. However, when both wood-boring beetles and high severity of plant pathogen infection occurred together, mountain pine beetle escaped from competition and improved its performance (increased brood production and feeding). Species-specific responses to changes in tree defense compounds and quality of resources (available phloem) were likely mechanisms driving this change of interactions between the two beetle groups. This is the first study demonstrating that a parasitic plant can be an important force in mediating competition among resource-sharing subcortical insect herbivores. PMID- 26820564 TI - Redox homeostasis: The Golden Mean of healthy living. AB - The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve "reactive oxygen species" rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles (parahormesis). In summary, while hormesis, although globally protective, results in setting up of a new phenotype, parahormesis contributes to health by favoring maintenance of homeostasis. PMID- 26820568 TI - Downregulated microRNA-23b promotes BMP9-mediated osteogenesis in C2C12 myoblast cells by targeting Runx2. AB - MicroRNAs are identified as negative regulators in gene expression through silencing gene expression at the post-transcriptional and translational levels. Bone morphogenetic protein 9 (BMP9) is the most effective in inducing osteogenesis in the BMP family, the members of which were originally identified as osteoinductive cytokines. In the current study, the role of miR-23b in the progression of BMP9-induced C2C12 myoblasts was investigated. The results indicated that miR-23b was significantly downregulated in C2C12 myoblasts induced by BMP9. Overexpression of miR-23b significantly inhibited osteogenesis in the C2C12 myoblasts. In addition, it was observed that Runx2 was negatively regulated by miR-23b at the post-transcriptional level, via a specific target site within the 3'UTR of Runx2. Knockdown of Runx2 promoted miR-23b-induced inhibition of osteogenesis in C2C12 myoblasts. The expression of Runx2 was observed to be frequently upregulated in osteoblast cell lines and inversely correlated with miR 23b expression. Thus, the results of the present study suggest that miR-23b inhibits BMP9-induced C2C12 myoblast osteogenesis via targeting of the Runx2 gene, acting as a suppressor. The current study contributes to the understanding of the functions of BMP9 in ossification. PMID- 26820569 TI - Susceptibility Factors Relevant for the Association Between Long-Term Air Pollution Exposure and Incident Asthma. AB - In this review, we identified 15 studies in children and 10 studies in adults that assessed the association between long-term exposure to air pollution and incident asthma and that conducted stratified analyses to explore potential susceptibility factors. Overall, adult never-/former smokers seem to be at higher risk of incident asthma due to air pollution. Children without atopy and children from low socioeconomic status families also seem to be at higher risk of incident asthma due to air pollution. While interaction between air pollution and genes involved in the response to oxidative stress pathways have been explored, results are somewhat inconsistent and in need of replication. To evaluate interactions, large sample sizes are necessary, and much more research, including data pooling from existing studies, is needed to further explore susceptibility factors for asthma incidence due to long-term air pollution exposure. PMID- 26820571 TI - Downregulation of a barley (Hordeum vulgare) leucine-rich repeat, non-arginine aspartate receptor-like protein kinase reduces expression of numerous genes involved in plant pathogen defense. AB - Pattern recognition receptors represent a first line of plant defense against pathogens. Comparing the flag leaf transcriptomes of barley (Hordeum vulgare L.) near-isogenic lines varying in the allelic state of a locus controlling senescence, we have previously identified a leucine-rich repeat receptor-like protein kinase gene (LRR-RLK; GenBank accession: AK249842), which was strongly upregulated in leaves of early-as compared to late-senescing germplasm. Bioinformatic analysis indicated that this gene codes for a subfamily XII, non arginine-aspartate (non-RD) LRR-RLK. Virus-induced gene silencing resulted in a two-fold reduction of transcript levels as compared to controls. Transcriptomic comparison of leaves from untreated plants, from plants treated with virus only without any plant sequences (referred to as 'empty virus' control), and from plants in which AK249842 expression was knocked down identified numerous genes involved in pathogen defense. These genes were strongly induced in 'empty virus' as compared to untreated controls, but their expression was significantly reduced (again compared to 'empty virus' controls) when AK249842 was knocked down, indicating that their expression partially depends on the LRR-RLK investigated here. Expression analysis, using datasets from BarleyBase/PLEXdb, demonstrated that AK249842 transcript levels are heavily influenced by the allelic state of the well-characterized mildew resistance a (Mla) locus, and that the gene is induced after powdery mildew and stem rust infection. Together, our data suggest that AK249842 is a barley pattern recognition receptor with a tentative role in defense against fungal pathogens, setting the stage for its full functional characterization. PMID- 26820570 TI - The P21-activated kinase expression pattern is different in non-small cell lung cancer and affects lung cancer cell sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors. AB - Exploring methods for increasing epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) sensitivity has become a major focus in non-small cell lung cancer (NSCLC). Major downstream effectors of the Rho family small guanosine triphosphatases, P21-activated kinases (PAKs) activate the main signaling pathways downstream of EGFR and thus promote tumor cell proliferation. In this study, we explored the expression pattern of phosphorylated PAKs in NSCLC and their potential value as drug targets for treating cancer. The expression and prognostic significance of phosphorylated group I and II PAKs were evaluated in 182 patients with NSCLC. Immunohistochemical analysis revealed low group I PAK expression in normal lung tissues and increased expressed in the cytoplasm, particularly in lung squamous cell carcinoma. Abnormal group I PAK expression was associated with lymph node metastases and high tumor-node-metastases (TNM) stage in NSCLC patients and correlated with poor prognosis. We used group I PAK inhibitor (IPA3) to specifically decrease group I PAK activity in human lung cancer cell lines. Decreased group I PAK activity inhibited cell proliferation and combined IPA3 and EGFR-TKI (gefitinib) treatment inhibited cell proliferation in an obvious manner. Together, our results revealed the PAK expression pattern in NSCLC, and a role for group I PAK in cell proliferation, which provides evidence that decreased PAK activity may have a potential application as a molecular targeted therapy in advanced NSCLC. PMID- 26820572 TI - "When the honeymoon is over, the real work begins:" Gastric bypass patients' weight loss trajectories and dietary change experiences. AB - To understand gastric bypass patients' experiences with managing food and eating for long-term weight management, this study examined patients' self-reported dietary changes and weight loss patterns. Thirteen women and three men between 15 months and 10 years post-gastric bypass surgery were recruited in Upstate New York. They completed two qualitative, in-depth interviews about their weight loss and dietary experiences. Using verbatim transcripts, researchers created timelines for each participant that summarized weight changes and the associated dietary behaviors. Constant comparative analysis of the timelines and transcripts identified a common, initial rapid weight loss period followed by weight stabilization, after which participants' weight loss patterns diverged into three possible long-term trajectories (Maintaining, Regained/Losing, and Regained) and one short-term trajectory (Losing). Dietary management over the periods of weight loss involved six components: physical needs, hunger and fullness, relationship with food, strategy use, habit formation, and awareness of eating. In the "honeymoon period" weight loss was "easy" because "surgery does the work" in limiting appetite, portion sizes, and interest in foods. As weight stabilized, "the work begins" as participants became capable of eating a greater quantity and a wider variety of foods. Differences in weight loss trajectories were associated with participants' abilities to maintain changes in relationship with food, dietary strategies and habits, and awareness of eating behaviors. Viewing weight loss outcomes of gastric bypass surgery as trajectories that develop as the result of dietary transitions and changes in dietary management suggests that patients need to be counseled on a variety of cognitive and behavioral strategies. PMID- 26820573 TI - Housing tenure and affordability and mental health following disability acquisition in adulthood. AB - Acquiring a disability in adulthood is associated with a reduction in mental health and access to secure and affordable housing is associated with better mental health. We hypothesised that the association between acquisition of disability and mental health is modified by housing tenure and affordability. We used twelve annual waves of data (2001-2012) (1913 participants, 13,037 observations) from the Household, Income and Labour Dynamics in Australia survey. Eligible participants reported at least two consecutive waves of disability preceded by two consecutive waves without disability. Effect measure modification, on the additive scale, was tested in three fixed-effects linear regression models (which remove time-invariant confounding) which included a cross-product term between disability and prior housing circumstances: housing tenure by disability; housing affordability by disability and, in a sub-sample (896 participants 5913 observations) with housing costs, tenure/affordability by disability. The outcome was the continuous mental component summary (MCS) of SF 36. Models adjusted for time-varying confounders. There was statistical evidence that prior housing modified the effect of disability acquisition on mental health. Our findings suggested that those in affordable housing had a -1.7 point deterioration in MCS (95% CI -2.1, -1.3) following disability acquisition and those in unaffordable housing had a -4.2 point reduction (95% CI -5.2, -1.4). Among people with housing costs, the largest declines in MCS were for people with unaffordable mortgages (-5.3, 95% CI -8.8, -1.9) and private renters in unaffordable housing (-4.0, 95% CI -6.3, -1.6), compared to a -1.4 reduction (95% CI -2.1, -0.7) for mortgagors in affordable housing. In sum, we used causally robust fixed-effects regression and showed that deterioration in mental health following disability acquisition is modified by prior housing circumstance with the largest negative associations found for those in unaffordable housing. Future research should test whether providing secure, affordable housing when people acquire a disability prevents deterioration in mental health. PMID- 26820574 TI - The value of reducing HIV stigma. AB - HIV-stigma is a major reason why HIV continues to be a global epidemic. Interventions targeting HIV-stigma are therefore necessary. To find an intervention that is worthwhile, a Cost-Benefit Analysis is needed which compares costs and benefits. There are many documented costs of HIV-stigma. What is missing is a valuation of the benefits of reducing HIV-stigma. The purpose of this paper is to present a general method that can be used to value the benefits of stigma reduction programs. The method involves estimating the marginal rate of substitution (MRS) between stigma and income in the utility function of older people with HIV. To illustrate how our framework can be used, we applied it to a sample of just over 900 people coming from the 2005-06 ROAH study (Research on Older Adults with HIV) in New York City. PMID- 26820575 TI - A Study of Alterations in DNA Epigenetic Modifications (5mC and 5hmC) and Gene Expression Influenced by Simulated Microgravity in Human Lymphoblastoid Cells. AB - Cells alter their gene expression in response to exposure to various environmental changes. Epigenetic mechanisms such as DNA methylation are believed to regulate the alterations in gene expression patterns. In vitro and in vivo studies have documented changes in cellular proliferation, cytoskeletal remodeling, signal transduction, bone mineralization and immune deficiency under the influence of microgravity conditions experienced in space. However microgravity induced changes in the epigenome have not been well characterized. In this study we have used Next-generation Sequencing (NGS) to profile ground based "simulated" microgravity induced changes on DNA methylation (5 methylcytosine or 5mC), hydroxymethylation (5-hydroxymethylcytosine or 5hmC), and simultaneous gene expression in cultured human lymphoblastoid cells. Our results indicate that simulated microgravity induced alterations in the methylome (~60% of the differentially methylated regions or DMRs are hypomethylated and ~92% of the differentially hydroxymethylated regions or DHMRs are hyperhydroxymethylated). Simulated microgravity also induced differential expression in 370 transcripts that were associated with crucial biological processes such as oxidative stress response, carbohydrate metabolism and regulation of transcription. While we were not able to obtain any global trend correlating the changes of methylation/ hydroxylation with gene expression, we have been able to profile the simulated microgravity induced changes of 5mC over some of the differentially expressed genes that includes five genes undergoing differential methylation over their promoters and twenty five genes undergoing differential methylation over their gene-bodies. To the best of our knowledge, this is the first NGS-based study to profile epigenomic patterns induced by short time exposure of simulated microgravity and we believe that our findings can be a valuable resource for future explorations. PMID- 26820576 TI - Increased Odds of Melanoma: Parkinson's Disease, Essential Tremor, Dystonia versus Controls. AB - OBJECTIVE: Patients with Parkinson's disease (PD) have an increased risk of melanoma, although the mechanisms are unclear. We are unaware of studies that have assessed the association between other movement disorders, such as essential tremor (ET) and dystonia, and melanoma. In this study, we assessed the association between ET, PD, dystonia and cancer (esp. melanoma). METHODS: One hundred and eight PD cases, 139 ET cases, and 54 dystonia cases, and 124 controls were enrolled in a research study of the epidemiology of movement disorders (total n = 425). The groups were frequency matched on age and gender. Cancer diagnoses were made based on self-reports. Melanoma diagnoses were further validated. RESULTS: The prevalence of melanoma was higher in PD cases than controls (13.9 vs. 1.6%, p < 0.001), and was marginally higher in ET cases (5.8%, p = 0.08) and dystonia cases (7.4%, p = 0.06) than controls. In adjusted logistic regression models, the odds of melanoma was 7.09-9.84 times higher in PD cases than controls (p values 0.01-0.003), 3.73-4.10 times higher in ET cases than controls (p values 0.08-0.10), and 4.88-5.27 times higher in dystonia cases than controls (p values 0.06-0.07). CONCLUSION: The links between neurological disorders and melanoma, long-known, may not be specific to PD and may extend to other movement disorders. PMID- 26820578 TI - The Epidural Treatment of Sciatica: Its Origin and Evolution. AB - Epidural injection with corticosteroids is a common treatment option for patients with lower back pain or sciatica. In this paper we review its origin and evolution. The first injections were given around 1900 in Paris by Jean Sicard (1872-1929) and Fernand Cathelin (1873-1945), who worked independently. They both injected small volumes of cocaine into the sacral hiatus. After a slow start, the epidural treatment of back pain and sciatica gradually spread to other parts of Europe and Northern America. In the early 1950s, corticosteroids were introduced for epidural use. Since the 1970s, there have been numerous clinical trials that show a significant, although small, effect of epidural corticosteroid injections compared with placebo for leg pain in the short term. Despite an ongoing debate about effectiveness and safety, epidural injections remain popular. PMID- 26820577 TI - Global Disorders of Sex Development Update since 2006: Perceptions, Approach and Care. AB - The goal of this update regarding the diagnosis and care of persons with disorders of sex development (DSDs) is to address changes in the clinical approach since the 2005 Consensus Conference, since knowledge and viewpoints change. An effort was made to include representatives from a broad perspective including support and advocacy groups. The goal of patient care is focused upon the best possible quality of life (QoL). The field of DSD is continuously developing. An update on the clinical evaluation of infants and older individuals with ambiguous genitalia including perceptions regarding male or female assignment is discussed. Topics include biochemical and genetic assessment, the risk of germ cell tumor development, approaches to psychosocial and psychosexual well-being and an update on support groups. Open and on-going communication with patients and parents must involve full disclosure, with the recognition that, while DSD conditions are life-long, enhancement of the best possible outcome improves QoL. The evolution of diagnosis and care continues, while it is still impossible to predict gender development in an individual case with certainty. Such decisions and decisions regarding surgery during infancy that alters external genital anatomy or removes germ cells continue to carry risk. PMID- 26820579 TI - Are Early Relapses in Advanced-Stage Ovarian Cancer Doomed to a Poor Prognosis? AB - OBJECTIVE: Early recurrence (ER) after completion of therapeutic regimen in advanced-stage ovarian cancer is a challenging clinical situation. Patients are perceived as invariably having a poor prognosis. We investigated the possibility of defining different prognostic subgroups and the parameters implicated in prognosis of ER patients. STUDY DESIGN: We analyzed a multi-centric database of 527 FIGO stage IIIC and IV ovarian cancer patients. We defined patients relapsing within 12 months as ER and investigated using Cox logistic regression the prognostic factors in ER group. We subsequently divided ER patients into good and poor prognosis groups according to a lower or higher overall survival (OS) at 12 months after relapse and determined parameters associated to poor prognosis. RESULTS: The median follow up was 49 months. One hundred and thirty eight patients recurred within 12 months. OS and Disease Free Survival (DFS) were 24.6 and 8.6 months, respectively, in this group of patients. Among the ER patients, 73 had a poor prognosis with an OS after relapse below 12 months (mean OS = 5.2 months) and 65 survived after one year (mean OS = 26.9 months). Residual disease (RD) after debulking surgery and mucinous histological subtype negatively impacted prognosis (HR = 1.758, p = 0.017 and HR = 8.641, p = 0.001 respectively). The relative risk of death within 12 months following relapse in ER patients was 1.61 according to RD status. However, RD did not affect DFS (HR = 0.889, p = 0.5). CONCLUSION: ER in advanced-stage ovarian cancer does not inevitably portend a short-term poor prognosis. RD status after initial cytoreduction strongly modulates OS, that gives additional support to the concept of maximum surgical effort even in patients who will experience early recurrence. The heterogeneity in outcomes within the ER group suggests a role for tumor biology in addition to classical clinical parameters. PMID- 26820580 TI - Assessment of cortical damage in early multiple sclerosis with quantitative T2 relaxometry. AB - T2 relaxation time is a quantitative MRI in vivo surrogate of cerebral tissue damage in multiple sclerosis (MS) patients. Cortical T2 prolongation is a known feature in later disease stages, but has not been demonstrated in the cortical normal appearing gray matter (NAGM) in early MS. This study centers on the quantitative evaluation of the tissue parameter T2 in cortical NAGM in a collective of early MS and clinically isolated syndrome (CIS) patients, hypothesizing that T2 prolongation is already present at early disease stages and variable over space, in line with global and focal inflammatory processes in MS. Additionally, magnetization transfer ratio (MTR) mapping was performed for further characterization of the expected cortical T2 alteration. Quantitative T2 and MTR maps were acquired from 12 patients with CIS and early MS, and 12 matched healthy controls. The lesion-free part of the cortical volume was identified, and the mean T2 and MTR values and their standard deviations within the cortical volume were determined. For evaluation of spatial specificity, cortical lobar subregions were tested separately for differences of mean T2 and T2 standard deviation. We detected significantly prolonged T2 in cortical NAGM in patients. T2 prolongation was found across the whole cerebral cortex and in all individual lobar subregions. Significantly higher standard deviations across the respective region of interest were found for the whole cerebral cortex and all subregions, suggesting the occurrence of spatially inhomogeneous cortical damage in all regions studied. A trend was observed for MTR reduction and increased MTR variability across the whole cortex in the MS group, suggesting demyelination. In conclusion, our results suggest that cortical damage in early MS is evidenced by spatially inhomogeneous T2 prolongation which goes beyond demyelination. Iron deposition, which is known to decrease T2, seems less prominent. PMID- 26820581 TI - Dynamic Growth of Pinhole-Free Conformal CH3NH3PbI3 Film for Perovskite Solar Cells. AB - Two-step dipping is one of the popular low temperature solution methods to prepare organic-inorganic halide perovskite (CH3NH3PbI3) films for solar cells. However, pinholes in perovskite films fabricated by the static growth method (SGM) result in low power conversion efficiency (PCE) in the resulting solar cells. In this work, the static dipping process is changed into a dynamic dipping process by controlled stirring PbI2 substrates in CH3NH3I isopropanol solution. The dynamic growth method (DGM) produces more nuclei and decreases the pinholes during the nucleation and growth of perovskite crystals. The compact perovskite films with free pinholes are obtained by DGM, which present that the big perovskite particles with a size of 350 nm are surrounded by small perovskite particles with a size of 50 nm. The surface coverage of the perovskite film is up to nearly 100%. Such high quality perovskite film not only eliminated pinholes, resulting in reduced charge recombination of the solar cells, but also improves the light harvesting efficiency. As a result, the PCE of the perovskite solar cells is increased from 11% for SGM to 13% for DGM. PMID- 26820582 TI - Endothelium-dependent hyperpolarizations: Quo vadis? PMID- 26820583 TI - Feed, supplements and contamination risks under FEI Rules: Insight from the Guerdat and Bichsel decisions. PMID- 26820584 TI - Questionnaire survey response rates in equine research. PMID- 26820585 TI - The search for the engram in eyeblink conditioning: A synopsis of past and present perspectives on the role of the cerebellum. AB - One of the most prolific behavioral neuroscientists of his generation, Richard F. Thompson published more than 450 research articles during his almost 60-year career before his death in 2014. The breadth and reach of his scholarship has extended to a large multidisciplinary audience of scientists. The focal point of this article is arguably his most influential paper on cerebellar classical conditioning entitled "The Neurobiology of Learning and Memory" that appeared in Science in 1986 and has been cited 700 times since its publication. Here, a summary of the initial Thompson laboratory research leading up to an understanding of the cerebellum and its critical role in memory traces will be discussed, along with conclusions from the Science article pertinent to cerebellar classical conditioning. The summary will also discuss how the original 1986 article continues to stimulate and influence new research and provide further insights into the role of the cerebellum in the neurobiology of learning and memory function relevant to studies of mammalian classical conditioning. (PsycINFO Database Record PMID- 26820586 TI - Ventromedial prefrontal theta activity during rapid eye movement sleep is associated with improved decision-making on the Iowa Gambling Task. AB - Recent research is beginning to reveal an intricate relationship between sleep and decision-making. The Iowa Gambling Task (IGT) is a unique decision-making task that relies on the ventromedial prefrontal cortex (vmPFC), an area that integrates and weighs previous experiences with reward and loss to select choices with the highest overall value. Recently, it has been demonstrated that a period of sleep can enhance decision-making on this task. Our study investigated the sleep mechanisms (sleep stages and cortical activity) that underlie this improvement. We recorded electrophysiology for 3 consecutive nights: a habituation, baseline, and acquisition night. On acquisition night participants were administered either a 200-trial IGT (IGT group; n = 13) or a 200-trial control (IGT-control group; n = 8) version of the task prior to sleep. Compared with baseline, the IGT group had a significant increase in theta frequency (4 Hz 8 Hz) on cites located above vmPFC and left prefrontal cortex during REM sleep. This increase correlated with subsequent performance improvement from deck B, a high reward deck with negative long-term outcomes. Furthermore, presleep emotional arousal (measured via skin conductance response) toward deck B correlated to increased theta activity above the right vmPFC during REM sleep. Overall, these results suggests that insight into deck B may be enhanced via vmPFC theta activity during REM sleep and REM sleep may have distinct mechanisms for processing decision-making information. (PsycINFO Database Record PMID- 26820588 TI - The effect of MDMA on sensitivity to reinforcement rate. AB - Administration of (+/-)3,4-methylenedioxymethamphetamine (MDMA) causes memory errors by increasing proactive interference. This might occur because MDMA alters sensitivity to reinforcement. The current 2 experiments investigated this directly by assessing the acute (Experiment 1) and chronic (Experiment 2) effects of MDMA on sensitivity to reinforcement. We presented 5 pairs of concurrent variable interval schedules within each session and calculated sensitivity to reinforcement for 3 acute doses of MDMA. In contrast to the related drug, d amphetamine, and in spite of producing reductions in response rate, MDMA did not reduce sensitivity to reinforcement rate. Chronic administration of a fixed dose of MDMA following each session reduced response rate but did not affect sensitivity to reinforcement rate. In combination with previous research, these results indicate that related drugs may have different effects on sensitivity to reinforcement and that these effects should be considered when interpreting disruptions to operant task performance caused by drug administration. (PsycINFO Database Record PMID- 26820590 TI - Announcement: Fifty Years of Global Immunization at CDC - 1966-2015. PMID- 26820587 TI - Limbic system development underlies the emergence of classical fear conditioning during the third and fourth weeks of life in the rat. AB - Classical fear conditioning creates an association between an aversive stimulus and a neutral stimulus. Although the requisite neural circuitry is well understood in mature organisms, the development of these circuits is less well studied. The current experiments examine the ontogeny of fear conditioning and relate it to neuronal activation assessed through immediate early gene (IEG) expression in the amygdala, hippocampus, perirhinal cortex, and hypothalamus of periweanling rats. Rat pups were fear conditioned, or not, during the third or fourth weeks of life. Neuronal activation was assessed by quantifying expression of FBJ osteosarcoma oncogene (FOS) using immunohistochemistry (IHC) in Experiment 1. Fos and early growth response gene-1 (EGR1) expression was assessed using qRT PCR in Experiment 2. Behavioral data confirm that both auditory and contextual fear continue to emerge between PD 17 and 24. The IEG expression data are highly consistent with these behavioral results. IHC results demonstrate significantly more FOS protein expression in the basal amygdala of fear-conditioned PD 23 subjects compared to control subjects, but no significant difference at PD 17. qRT-PCR results suggest specific activation of the amygdala only in older subjects during auditory fear expression. A similar effect of age and conditioning status was also observed in the perirhinal cortex during both contextual and auditory fear expression. Overall, the development of fear conditioning occurring between the third and fourth weeks of life appears to be at least partly attributable to changes in activation of the amygdala and perirhinal cortex during fear conditioning or expression. (PsycINFO Database Record PMID- 26820589 TI - Sleep quality and depressive symptoms after prostate cancer: The mechanistic role of cortisol. AB - A substantial portion of men treated for prostate cancer report clinically significant sleep problems and disturbance in sleep quality constitutes significant risk for the development of depressive symptoms in survivors. Dysregulation in biological stress processes underlies the impact of poor sleep on the onset and/or progression of depressive symptoms, yet few studies have sought to identify potential neurobiological mechanisms (e.g., HPA axis activation) underlying this association in PC survivors. The present study examines the relationships between sleep disturbance, depressive symptoms, and indices of diurnal cortisol patterns among men treated for prostate cancer. In total, 66 men (84.8% White; mean age = 65.8 years, SD = 9.04) treated in the prior 2 years for localized prostate cancer were recruited. They completed questionnaires to measure sleep quality and depressive symptoms at study entry (T1) and 4 months later (T2). They also provided 4 saliva samples per day, over 3 days, at T1. Three cortisol indices were computed: diurnal slope, area under the curve (AUCg), and cortisol awakening response (CAR). Analyses indicate that, controlling for body mass index and age, worse sleep quality at T1 was significantly associated with higher levels of depressive symptoms at T2. Significant indirect effects were observed for cortisol slope (indirect effect = .17, 95% CI [-.61, -.01]) and AUCg (indirect effect = -.14, 95% CI [-.43, -.01]), but not CAR. Results suggest that dysregulation in HPA activity acts as a neurobiological mechanism of the impact of sleep disruption on depressive symptoms in men with prostate cancer. (PsycINFO Database Record PMID- 26820591 TI - BK polyomavirus genotypes and nephropathy: is there a relationship? PMID- 26820593 TI - ST6GalNAcII mediates tumor invasion through PI3K/Akt/NF-kappaB signaling pathway in follicular thyroid carcinoma. AB - Altered sialylation, closely associated with tumor progression and metastasis, has been implicated in human thyroid carcinoma. The present study investigated the alteration in expression of ST6GalNAcII involved in invasion and to clarify the possible mechanism of ST6GalNAcII in the metastasis process in human follicular thyroid carcinoma cell lines. Using real-time PCR, western blot and IHC analysis, ST6GalNAcII differed in three follicular thyroid cancer cell lines (FTC133, primary and FTC238, lung metastasis). It also showed differential expression in follicular thyroid carcinoma and tissue specimens. In addition, we analyzed the PI3K/Akt signaling pathway. The altered expression of ST6GalNAcII corresponded to changed invasive phenotype of FTC-238 and FTC-133 cells in vitro and in vivo. Further studies showed that regulating ST6GalNAcII expression markedly modulated the activity of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Targeting the PI3K/Akt pathway by its specific inhibitor LY294002, or by Akt small interfering RNA (siRNA) resulted in reduced capacity in invasion of FTC-238. In conclusion, taken together, our results imply that ST6GalNAcII activated the invasion in follicular thyroid cancer cells through regulating the activity of PI3K/Akt pathway. PMID- 26820592 TI - Effect of Cocaine on Pulmonary Vascular Remodeling and Hemodynamics in Human Immunodeficiency Virus-Transgenic Rats. AB - Human immunodeficiency virus (HIV)-related pulmonary arterial hypertension has been found to be more prevalent in intravenous drug users. Our earlier cell culture findings reported down-regulation of bone morphogenetic protein receptors (BMPRs) in combination with enhanced proliferation of human pulmonary arterial smooth muscle cells (PASMCs) in the presence of HIV-Trans-activator of transcription (Tat) and cocaine compared with either treatment alone. Here, we report physiologic evidence of significant increases in mean pulmonary arterial pressure in HIV-transgenic (Tg) rats intraperitoneally administered 40 mg/kg body weight cocaine (HIV-cocaine group) once daily for 21 days when compared with HIV Tg rats given saline (HIV group) or wild-type (WT) Fischer 334 rats treated with (WT-cocaine group) and without cocaine (WT group). In addition, right ventricle systolic pressure was also found to be significantly higher in the HIV-cocaine rats compared with the WT group. Significant down-regulation in protein expression of BMPR-2 and BMPR-1B was observed in total lung extract from HIV cocaine rats compared with the other three groups. Furthermore, the PASMCs isolated from HIV-cocaine rats demonstrated a higher level of proliferation and lower levels of apoptosis compared with cells isolated from other rat groups. Interestingly, corroborating our earlier cell-culture findings, we observed higher expression of BMPR-2 and BMPR-1B messenger RNA and significantly lower levels of BMPR-2 and BMPR-1B protein in HIV-cocaine PASMCs compared with cells isolated from all other groups. In conclusion, our findings support an additive effect of cocaine and HIV on smooth muscle dysfunction, resulting in enhanced pulmonary vascular remodeling with associated elevation of mean pulmonary arterial pressure and right ventricle systolic pressure in HIV-Tg rats exposed to cocaine. PMID- 26820594 TI - Tamoxifen promotes differentiation of oligodendrocyte progenitors in vitro. AB - The most promising therapeutic approach to finding the cure for devastating demyelinating conditions is the identification of clinically safe pharmacological agents that can promote differentiation of endogenous oligodendrocyte precursor cells (OPCs). Here we show that the breast cancer medication tamoxifen (TMX), with well-documented clinical safety and confirmed beneficial effects in various models of demyelinating conditions, stimulates differentiation of rat glial progenitors to mature oligodendrocytes in vitro. Clinically applicable doses of TMX significantly increased both the number of CNPase-positive oligodendrocytes and protein levels of myelin basic protein, measured with Western blots. Furthermore, we also found that OPC differentiation was stimulated, not only by the pro-drug TMX-citrate (TMXC), but also by two main TMX metabolites, 4-hydroxy TMX and endoxifen. Differentiating effects of TMXC and its metabolites were completely abolished in the presence of estrogen receptor (ER) antagonist, ICI182780. In contrast to TMXC and 4-hydroxy-TMX, endoxifen also induced astrogliogenesis, but independent of the ER activation. In sum, we showed that the TMX prodrug and its two main metabolites (4-hydroxy-TMX and endoxifen) promote ER-dependent oligodendrogenesis in vitro, not reported before. Given that differentiating effects of TMX were achieved with clinically safe doses, TMX is likely one of the most promising FDA-approved drugs for the possible treatment of demyelinating diseases. PMID- 26820595 TI - Tissue-type plasminogen activator induces synaptic vesicle endocytosis in cerebral cortical neurons. AB - The release of the serine proteinase tissue-type plasminogen activator (tPA) from the presynaptic terminal of cerebral cortical neurons plays a central role in the development of synaptic plasticity, adaptation to metabolic stress and neuronal survival. Our earlier studies indicate that by inducing the recruitment of the cytoskeletal protein betaII-spectrin and voltage-gated calcium channels to the active zone, tPA promotes Ca(2+)-dependent translocation of synaptic vesicles (SVs) to the synaptic release site where they release their load of neurotransmitters into the synaptic cleft. Here we used a combination of in vivo and in vitro experiments to investigate whether this effect leads to depletion of SVs in the presynaptic terminal. Our data indicate that tPA promotes SV endocytosis via a mechanism that does not require the conversion of plasminogen into plasmin. Instead, we show that tPA induces calcineurin-mediated dynamin I dephosphorylation, which is followed by dynamin I-induced recruitment of the actin-binding protein profilin II to the presynaptic membrane, and profilin II induced F-actin formation. We report that this tPA-induced sequence of events leads to the association of newly formed SVs with F-actin clusters in the endocytic zone. In summary, the data presented here indicate that following the exocytotic release of neurotransmitters tPA activates the mechanism whereby SVs are retrieved from the presynaptic membrane and endocytosed to replenish the pool of vesicles available for a new cycle of exocytosis. Together, these results indicate that in murine cerebral cortical neurons tPA plays a central role coupling SVs exocytosis and endocytosis. PMID- 26820596 TI - A randomized, placebo-controlled trial of the benzoquinone idebenone in a mouse model of OPA1-related dominant optic atrophy reveals a limited therapeutic effect on retinal ganglion cell dendropathy and visual function. AB - Dominant optic atrophy (DOA) arises from mutations in the OPA1 gene that promotes fusion of the inner mitochondrial membrane and plays a role in maintaining ATP levels. Patients display optic disc pallor, retinal ganglion cell (RGC) loss and bilaterally reduced vision. We report a randomized, placebo-controlled trial of idebenone at 2000 mg/kg/day in 56 Opa1 mutant mice (B6;C3-Opa1(Q285STOP)), with RGC dendropathy and visual loss, and 63 wildtype mice. We assessed cellular responses in the retina, brain and liver and RGC morphology, by diolistic labeling, Sholl analysis and quantification of dendritic morphometric features. Vision was assessed by optokinetic responses. ATP levels were raised by 0.57 nmol/mg (97.73%, p=0.035) in brain from idebenone-treated Opa1 mutant mice, but in the liver there was an 80.35% (p=0.011) increase in oxidative damage. NQO1 expression in Opa1 mutant mice was reduced in the brain (to 30.5%, p=0.002) but not in retina, and neither expression level was induced by idebenone. ON-center RGCs failed to show major recovery, other than improvements in secondary dendritic length (by 53.89%, p=0.052) and dendritic territory (by 2.22 * 10(4) MUm(2) or 90.24%, p=0.074). An improvement in optokinetic response was observed (by 12.2 +/- 3.2s, p=0.003), but this effect was not sustained over time. OFF center RGCs from idebenone-treated wildtype mice showed shrinkage in total dendritic length by 2.40 mm (48.05%, p=0.025) and a 47.37% diminished Sholl profile (p=0.029). Visual function in wildtype idebenone-treated mice was impaired (2.9 fewer head turns than placebo, p=0.007). Idebenone appears largely ineffective in protecting Opa1 heterozygous RGCs from dendropathy. The detrimental effect of idebenone in wildtype mice has not been previously observed and raises some concerns. PMID- 26820597 TI - Differential activation of dopaminergic systems in rat brain basal ganglia by morphine and methamphetamine. AB - Typical abused drug-induced behavioral changes are ordinarily mediated by the mesolimbic dopaminergic system and even the phenotypes of behavior are different from each other. However, the mechanisms that underlie the behavioral changes induced by these abused drugs have not yet been elucidated. The present study was designed to investigate the mechanisms that underlie how abused drugs induce distinct behavioral changes using neurochemical as well as behavioral techniques in rats. Methamphetamine (2mg/kg) more potently increased dopamine release from the striatum more than that from the nucleus accumbens. In contrast, the administration of morphine (10mg/kg) produced a significant increase in the release of dopamine from the nucleus accumbens, but not the striatum, which is accompanied by a decrease in the release of GABA in the ventral tegmental area. These findings indicate that morphine and methamphetamine differentially regulate dopaminergic systems to produce behavioral changes, even though both drugs have abuse potential through activation of the mesolimbic dopaminergic system. PMID- 26820598 TI - Exercise modulates synaptic acetylcholinesterase at neuromuscular junctions. AB - Acetylcholinesterase plays a major role in neuromuscular transmission and is regulated by neuromuscular activity. Since fast-twitch motor units are recruited with increased motor demand, we examined acetylcholinesterase regulation in rat leg muscles following treadmill training. Total acetylcholinesterase and specifically the membrane-bound tetramer increased in exercised fast-, but not slow-twitch muscles, while other isoforms remained unchanged. Synaptic acetylcholinesterase increased markedly in neuromuscular junctions of trained fibers, without concomitant changes in synaptic acetylcholine receptor, thus elevating synaptic acetylcholinesterase/receptor ratios. Electron microscopy showed that acetylcholinesterase increased in postjunctional folds and primary cleft, where it was added adjacent to the postsynaptic muscle membrane. Thus, although the primary acetylcholinesterase at the neuromuscular junction is the collagen-tailed asymmetric isoform associated with synaptic basal lamina, physiological demands such as strenuous exercise, or potentially pathological conditions, can selectively recruit the membrane-bound acetylcholinesterase tetramer to the synapse for optimal synaptic transmission. PMID- 26820599 TI - Increased levels of brain serotonin correlated with MMP-9 activity and IL-4 levels resulted in severe experimental autoimmune encephalomyelitis (EAE) in obese mice. AB - The aim of this study was to investigate the role of monoamine neurotransmitters on the severity of experimental autoimmune encephalomyelitis (EAE) in obese mice. EAE was induced in mice with normal diets (ND-EAE) and obese mice with high-fat diets (HFD-EAE) through the immune response to myelin oligodendrocyte glycoprotein (MOG) (35-55). The levels of dopamine (DA), serotonin (5-HT) and their metabolites in different anatomical brain regions were measured by high performance liquid chromatography. The plasma and tissue NADPH oxidase and matrix metalloproteinases (MMP)-9 activities were analyzed by fluorescence spectrophotometry. The cumulative disease index and disease peaks were significantly higher in HFD-EAE compared with those in ND-EAE. Significantly higher 5-HT levels and lower 5-HT turnovers 5-hydroxyindole acetic acid ((5 HIAA)/5-HT) were found in the brains of HFD-EAE mice compared with those found in the HFD-CON and ND-EAE mice brains. Moreover, increased DA levels were observed in the caudate nucleus of the HFD-EAE mice compared with the control and ND-EAE mice. The NADPH oxidase and MMP-9 activities in the plasma and tissues were significantly higher in both the ND-EAE and HFD-EAE groups than in their respective controls. The cytokine levels in the plasma, tissues, and cultured splenocytes were found to be significantly altered in EAE mice compared with control mice. Moreover, HFD-EAE mice exhibited significantly higher MMP-9 activity and lower IL-4 levels than ND-EAE mice and were significantly correlated with brain 5-HT levels. In conclusion, the increased 5-HT levels in the brain significantly correlated with MMP-9 activity and IL-4 levels play an important role in the exacerbation of disease severity in HFD-EAE mice. PMID- 26820600 TI - 1,25-Dihydroxyvitamin D3 regulates expression of LRP1 and RAGE in vitro and in vivo, enhancing Abeta1-40 brain-to-blood efflux and peripheral uptake transport. AB - Alzheimer's disease (AD) is characterized by the accumulation and deposition of plaques of amyloid-beta (Abeta) peptide in the brain. Growing epidemiological and experimental studies have shown that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) exerts neuroprotection against AD. However, the underlying mechanisms of the action remain unclear. Since Abeta clearance plays a crucial role in Abeta balance in the brain, the aim of the present study was to investigate potential effects of 1,25(OH)2D3 on Abeta1-40, the major soluble oligomeric form of Abeta, clearance via transport across blood-brain barrier (BBB) mediated by low-density lipoprotein receptor-related protein 1 (LRP1) (efflux) and receptor for advanced glycation end products (RAGE) (influx) and peripheral uptake by liver mediated by LRP1. We identified colocalization of LRP1 and RAGE at BBB of mice, established an in vitro BBB model by culturing monolayer mouse brain microvascular endothelial cell line (bEnd.3) cells under hypoxia and observed that 1,25(OH)2D3 treatment enhanced Abeta1-40 efflux across the BBB model and uptake by HepG2 cells. After 1,25(OH)2D3 exposure, LRP1 expression was increased significantly both in vivo and in vitro, and RAGE expression was reduced in the in vitro BBB model but not in microvascular endothelial cells of mice hippocampus. Additionally, we explored the correlation between the corresponding effects of 1,25(OH)2D3 and its nuclear hormone receptor vitamin D receptor (VDR) level. We found that VDR expression was upregulated after 1,25(OH)2D3 treatment both in vivo and in vitro. Collectively, our finding that 1,25(OH)2D3 reduces cerebral Abeta1-40 level by increasing Abeta1-40 brain-to-blood efflux and peripheral uptake through regulating LRP1 and RAGE could shed light on the mechanism of 1,25(OH)2D3 neuroprotection against AD. And the action of 1,25(OH)2D3 might be associated with the VDR pathway. PMID- 26820601 TI - Does platelet mass influence the effectiveness of ibuprofen treatment for patent ductus arteriosus in preterm infants? AB - OBJECTIVE: The aim of this study is to evaluate whether the platelet mass in the first 24 h of life is effective on closure of patent ductus arteriosus (PDA) or not. STUDY DESIGN: Preterm infants with a gestational age of < 32 weeks, hospitalized at a tertiary neonatal intensive care unit (NICU) and requiring medical treatment (intravenous or oral ibuprofen) for hemodinamically significant PDA (hsPDA) were enrolled in this study. The patients were divided into two groups after first course of pharmacologic treatment according to closure of PDA (Group 1: PDA closure, Group 2: PDA without closure). Groups were compared in terms of demographics findings, morbidities, platelet measurements like counts, mean platelet volume (MPV) and platelet mass (platelet count * mean platelet volume). RESULTS: The study included 77 preterm newborns in Group 1, and 30 preterms in Group 2. There were no differences in birth weight, gestational age, gender and maternal risk factors between the study groups. The mean platelet count in the first postnatal blood count was in Group 1: 211.3 +/- 89.2 * 10(3)/mm(3) and in Group 2: 216.5 +/- 26 * 10(3)/mm(3), respectively (p = 0.783). The mean platelet volumes (MPV) were similar in both groups (p = 0.535). No statistically significant difference between platelet mass values was detected (Group 1: 1811 +/- 884 fl/nl, Group 2: 1868 +/- 717 fl/nl) (p = 0.753). CONCLUSION: Our data suggest that platelet count, MPV and platelet mass did not affect the closure of hsPDA with ibuprofen. PMID- 26820602 TI - Interpretation of Ocular Melanin Drug Binding Assays. Alternatives to the Model of Multiple Classes of Independent Sites. AB - Melanin has a high binding affinity for a wide range of drugs. The determination of the melanin binding capacity and its binding affinity are important, e.g., in the determination of the ocular drug distribution, the prediction of drug effects in the eye, and the trans-scleral drug delivery. The binding parameters estimated from a given data set vary significantly when using different isotherms or different nonlinear fitting methods. In this work, the commonly used bi-Langmuir isotherm, which assumes two classes of independent sites, is confronted with the Sips isotherm. Direct, log-log, and Scatchard plots are used, and the interpretation of the binding curves in the latter is critically analyzed. In addition to the goodness of fit, the emphasis is placed on the physical meaning of the binding parameters. The bi-Langmuir model imposes a bimodal distribution of binding energies for the sites on the melanin granules, but the actual distribution is most likely continuous and unimodal, as assumed by the Sips isotherm. Hence, the latter describes more accurately the distribution of binding energies and also the experimental results of melanin binding to drugs and metal ions. Simulations are used to show that the existence of two classes of sites cannot be confirmed on the sole basis of the shape of the binding curve in the Scatchard plot, and that serious doubts may appear on the meaning of the binding parameters of the bi-Langmuir model. Experimental results of melanin binding to chloroquine and metoprolol are used to illustrate the importance of the choice of the binding isotherm and of the method used to evaluate the binding parameters. PMID- 26820603 TI - Tankyrase 1 inhibitior XAV939 increases chemosensitivity in colon cancer cell lines via inhibition of the Wnt signaling pathway. AB - Aberrant Wnt signaling pathway is associated with a wide array of tumor types and plays an important role in the drug resistance of cancer stem cells (CSCs). To explore the effects and mechanism of WNT signaling pathway inhibitor XAV939 on drug resistance in colon cancer cells, the colon cancer cells SW480 and SW620 were treated with 5-fluorouracil (5-FU)/cisplatin (DDP) alone or combined with XAV939. Cell cycle distribution, apoptosis level and the percentage of CD133+ cells were detected by flow cytometry. The protein expression of Axin, beta catenin, EpCAM, TERT and DCAMKL-1 was detected by western blotting. XAV939 upregulated Axin , decreased the total and nuclei of beta-catenin in SW480 and SW620 cells. Furthermore, XAV939 significantly downregulated the CSC markers EpCAM, TERT and DCAMKL-1 in SW480 cells, as well as EpCAM in SW620 cells. No significant difference was found in the apoptosis of SW480 and SW620 cells with XAV939 treatment, but XAV939 significantly increased apoptosis induced by 5 FU/DDP in SW480 cells, whereas, the effects were slight in SW620 cells. Collectively, we show for the first time that the WNT signaling pathway inhibitor XAV939 was able to significantly increase the apoptosis induced by 5-FU/DDP, accompanied by the protein expression level alternation of beta-catenin, Axin and CSC markers in colon cancer cells. Axin, an important component of Wnt/beta catenin signaling pathway could be a potential molecular target for reversing multidrug resistance in colon cancer. PMID- 26820604 TI - Internal medicine resident knowledge, attitudes, and barriers to naloxone prescription in hospital and clinic settings. AB - BACKGROUND: The United States is facing an epidemic of opioid use and misuse leading to historically high rates of overdose. Community-based overdose education and naloxone distribution has effectively trained lay bystanders to recognize signs of overdose and administer naloxone for reversal. There has been a movement to encourage physicians to prescribe naloxone to all patients at risk of overdose; however, the rate of physician prescribing remains low. This study aims to describe resident knowledge of overdose risk assessment, naloxone prescribing practices, attitudes related to naloxone, and barriers to overdose prevention and naloxone prescription. METHODS: The HOPE (Hospital-based Overdose Prevention and Education) Initiative is an educational campaign to teach internal medicine residents to assess overdose risk, provide risk reduction counseling, and prescribe naloxone. As part of a needs assessment, internal medicine residents at an academic medical center in Baltimore, Maryland, were surveyed in 2015. Data were collected anonymously using Qualtrics. RESULTS: Ninety-seven residents participated. Residents were overwhelmingly aware of naloxone (80%) and endorsed a willingness to prescribe (90%). Yet despite a high proportion of residents reporting patients in their panels at increased overdose risk (79%), few had prescribed naloxone (15%). Residents were willing to discuss overdose prevention strategies, although only a minority reported doing so (47%). The most common barriers to naloxone prescribing were related to knowledge gaps in how to prescribe and how to assess risk of overdose and identify candidates for naloxone (52% reporting low confidence in ability to identify patients who are at risk). CONCLUSIONS: Medicine residents are aware of naloxone and willing to prescribe it to at-risk patients. Due to decreased applied knowledge and limited self efficacy, few residents have prescribed naloxone in the past. In order to improve rates of physician prescribing, initiatives must help physicians better assess risk of overdose and improve prescribing self-efficacy. PMID- 26820606 TI - Sexual Function in Female Veterans: A Review. AB - Women comprise a significant proportion of the veteran population. Much research has been devoted to physical and mental health outcomes in veterans, both of which show significant decreases in quality of life. However, little is known about the effects of female veterans' unique military experience on sexual function. In particular, military sexual trauma, general military stressors, mental health diagnoses, and other vulnerability factors contribute to sexual dysfunction, dissatisfaction, and decreases in mental health-related quality of life. We propose a model whereby all of these factors interact and contribute to sexual dysfunction in female veterans, and areas for growth in assessment and treatment are discussed. PMID- 26820605 TI - A novel mutation in the SCN5A gene contributes to arrhythmogenic characteristics of early repolarization syndrome. AB - Several genetic variants have been associated with early repolarization syndrome (ERS). However, the lack of functional validations of the mutant effects has limited the interpretation of genetic tests. In the present study, we identified and characterized a novel sodium channel, voltage gated, type V alpha subunit (SCN5A) mutation that was associated with ERS. A 67-year-old male proband suffering from recurrent syncope underwent a documented electrocardiogram (ECG) for polymorphic ventricular tachycardia (VT). It was noted that baseline 12-lead ECG exhibited a predominantly elevated ST-segment which mimicked acute myocardial ischemia in lead V2-V6, and the ECG also demonstrated J waves in lead II, III, aVF and V2-V6. Using genetic analysis, we noted that the proband carried a novel heterozygous missense mutation of A1055G in the SCN5A gene. Whole-cell configuration of patch-clamp analysis revealed that the mutation significantly decreased peak sodium current (INa) density and shifted the steady-state inactivation curve of INa to a more negative potential. Confocal imaging suggested that in the mutant channel a defect of protein expression both on the cell membrane and in cytoplasm was present. The present study demonstrated that a novel heterozygous missense mutation of A1055G in SCN5A led to 'loss-of function' of the sodium channels, and we suggest that it accounts for the arrhythmogenic characteristics of ERS. PMID- 26820607 TI - Editorial. PMID- 26820609 TI - Identification and characterization of the intermediate phase in hybrid organic inorganic MAPbI3 perovskite. AB - Perovskite films were prepared using single step solution deposition at different annealing temperatures and annealing times. The crystal structure, phases and grain size were investigated with XRD, XPS and SEM/EDX. The prepared films show a typical orientation of tetragonal perovskite phase and a gradual transition at room temperature from the yellow intermediate phase to the black perovskite phase. Films with high purity were obtained by sintering at 100 degrees C. In addition, the chemical composition and crystal structure of intermediate phase were investigated in detail. FTIR, UV-vis and NMR spectra revealed the occurance of DMF complexes. Interestingly, the intermediate phase could be transformed to the black perovskite phase upon X-ray irradiation. In addition, the recovery of the aged perovskite films from a yellow intermediate phase back to the black perovskite was shown to be viable via heating and X-ray irradiation. PMID- 26820608 TI - Heterosexual Anal Sex Among Men and Women in Substance Abuse Treatment: Secondary Analysis of Two Gender-Specific HIV-Prevention Trials. AB - Receptive anal sex has high human immunodeficiency virus (HIV) transmission risk, and heterosexual substance-abusing individuals report higher anal sex rates compared to their counterparts in the general population. This secondary analysis evaluated the effectiveness of two gender-specific, evidence-based HIV-prevention interventions (Real Men Are Safe, or REMAS, for men; Safer Sex Skill Building, or SSSB, for women) against an HIV education (HIV-Ed) control condition on decreasing unprotected heterosexual anal sex (HAS) among substance abuse treatment-seeking men (n = 171) and women (n = 105). Two variables, engagement in any HAS and engagement in unprotected HAS, were assessed at baseline and three months postintervention. Compared to the control group, women in the gender specific intervention did not differ on rates of any HAS at follow-up but significantly decreased their rates of unprotected HAS. Men in both the gender specific and the control interventions reported less HAS and unprotected HAS at three-month follow-up compared to baseline, with no treatment condition effect. The mechanism of action for SSSB compared to REMAS in decreasing unprotected HAS is unclear. More attention to HAS in HIV-prevention interventions for heterosexual men and women in substance abuse treatment is warranted. PMID- 26820610 TI - Long-term intraocular pressure changes after intravitreal injection of bevacizumab. AB - PURPOSE: To assess the long-term intraocular pressure (IOP) changes after the intravitreal injection of bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) for treatment of age-related macular degeneration (AMD) and diabetic macular edema (DME) patients and evaluate the correlation factors. MATERIAL AND METHODS: Patients with neovascular AMD or DME underwent treat-and extended anti-VEGF regimen in one eye and followed more than 12 months were enrolled in this study. We set three criteria of IOP elevation: (1) the IOP of the treated eye increased above the contralateral eye for at least two consecutive visits; (2) the IOP of the treated eye increased above the pre injection IOP for at least two consecutive visits; (3) and the IOP of the treated eye increased more than 5 mmHg above the baseline IOP for at least two consecutive visits. We used mixed model univariate and multivariate analysis to assess the association between IOP elevation and independent parameters including age, sex, lens status, the number of injections, and underlying disease. RESULTS: In total 152 patients, 83 patients with AMD and 69 patients with DME, were included in this study. Mean follow-up time was 18.7 months, with a maximum of 50 months. In IOP elevation, 54 eyes (35.6%) showed an IOP increase above that of the contralateral eye (criteria 1), 50 eyes (33.4%) showed an IOP increase above the baseline IOP (criteria 2), and an IOP increase greater than 5 mmHg above the baseline IOP observed in nine eyes (5.9%) (criteria 3). In the univariate analysis, lens status and total number of injections were statistically significant for criteria 2 and 3 (all ps < 0.05). However, in the multivariable analysis, only the number of intravitreal injections was statistically correlated with sustained IOP elevation for criteria 2 and 3 (p < 0.001 and p = 0.039, respectively). CONCLUSIONS: Our results suggest that under long-term monitoring, with a treat-and-extended regimen, intravitreal bevacizumab injections were associated with sustained IOP elevation. In particular, multiple intravitreal injections could be associated with sustained IOP elevation. PMID- 26820611 TI - Estimation of the Unregistered Inflow of Electrical and Electronic Equipment to a Domestic Market: A Case Study on Televisions in Vietnam. AB - Waste electrical and electronic equipment (WEEE) constitutes one of the most problematic waste streams worldwide, and accurately estimating the scale of WEEE can assist in tackling its associated issues. However, obtaining an accurate estimation of WEEE remains a challenge because a share of the waste is difficult to calculate. This share stems from the administratively unregistered (so-called "invisible") inflow of electrical and electronic equipment (EEE) into the domestic market. As a first attempt to qualitatively and quantitatively investigate this invisible inflow, this study discusses the nature of this flow in detail and proposes a calculation pathway for quantifying its magnitude. The size of the invisible inflow to a domestic market (assumed equal to invisible sales) is calculated by subtracting the registered, also called "visible", sales from the total sales. The total sales are modeled, whereas the visible sales are derived from statistical data. The method is illustrated by a case study on televisions (TVs) in Vietnam. The results show that from 2002 to 2013, the invisible TV inflow contributed, on average, 15% to the total TV sales (coefficient of variation: 0.21). This average share would increase by approximately 1.0% when the maximum number of TVs used per household increased by 1.0%. However, it would decrease by 1.7% when the visible sales increased by 1.0%. Additionally, the average share of the invisible TV inflow would change from 15% to 27% when an unadjusted constant instead of an adjusted time-varying lifespan is employed. This first estimation of the invisible EEE inflow to the domestic market can be improved with additional knowledge and data in the future. PMID- 26820613 TI - Expression of MAGE-A1-A12 subgroups in the invasive tumor front and tumor center in oral squamous cell carcinoma. AB - MAGE-A proteins are highly expressed in oral squamous cell carcinoma (OSCC) and are promising targets for cancer immunotherapy. This study examined the presence of MAGE-A expression within the tumor center (TC) and tumor invasive front (TIF) and evaluated its relationship to poor prognosis. The expression rate of each MAGE-A subtype, A1-A12, was examined in 68 OSCCs at the TIF and TC. Slides (1-um) of tissue microarrays (diameter =0.6 mm) were immunohistochemically stained, and the findings were correlated to clinical data. Approximately 95% of the tumors had MAGE-A expression. Higher expression in the TC was shown significantly for MAGE-A1, -A5, -A6, -A9 and -A12 (P<0.05). MAGE-A2 and -A3 exhibited the opposite behavior (not significant, P>0.05). Age, tumor size, grade and survival time were not associated with the expression of certain MAGE-A subgroups. When expression in the whole tumor tissue was considered, only MAGE-A1 was expressed at a significantly higher rate in male patients (P=0.034). At the TIF, MAGE-A9 and the UICC disease stage were significantly correlated (P=0.0263), and MAGE-A6 and the UICC disease stage exhibited a strong trend (P=0.0596). The expression of MAGE A3, -A4, -A5, -A9 and -A11 was significantly associated with lymph node metastasis, while MAGE-A4 was expressed in all regions of the tumors (TIF and TC). This study showed that higher expression of most MAGE-A antigens occurred at the TC rather than at the TIF. MAGE-A1, -A3, -A4, -A5, -A9 and -A11 were significantly associated with clinically advanced stages of disease and seem to be of particular interest. PMID- 26820612 TI - Pre-Visit Prioritization for complex patients with diabetes: Randomized trial design and implementation within an integrated health care system. AB - BACKGROUND/AIMS: Despite robust evidence to guide clinical care, most patients with diabetes do not meet all goals of risk factor control. Improved patient provider communication during time-limited primary care visits may represent one strategy for improving diabetes care. METHODS: We designed a controlled, cluster randomized, multi-site intervention (Pre-Visit Prioritization for Complex Patients with Diabetes) that enables patients with poorly controlled type 2 diabetes to identify their top priorities prior to a scheduled visit and sends these priorities to the primary care physician progress note in the electronic medical record. In this paper, we describe strategies to address challenges to implementing our health IT-based intervention study within a large health care system. RESULTS: This study is being conducted in 30 primary care practices within a large integrated care delivery system in Northern California. Over a 12 week period (3/1/2015-6/6/2015), 146 primary care physicians consented to enroll in the study (90.1%) and approved contact with 2496 of their patients (97.6%). Implementation challenges included: (1) navigating research vs. quality improvement requirements; (2) addressing informed consent considerations; and (3) introducing a new clinical tool into a highly time-constrained workflow. Strategies for successfully initiating this study included engagement with institutional leaders, Institutional Review Board members, and clinical stakeholders at multiple stages both before and after notice of Federal funding; flexibility by the research team in study design; and strong support from institutional leadership for "self-learning health system" research. CONCLUSIONS: By paying careful attention to identifying and collaborating with a wide range of key clinical stakeholders, we have shown that researchers embedded within a learning care system can successfully apply rigorous clinical trial methods to test new care innovations. PMID- 26820614 TI - Human-Mouse Chimeras with Normal Expression and Function Reveal That Major Domain Swapping Is Tolerated by P-Glycoprotein (ABCB1). AB - The efflux transporter P-glycoprotein (P-gp) plays a vital role in the transport of molecules across cell membranes and has been shown to interact with a panoply of functionally and structurally unrelated compounds. How human P-gp interacts with this large number of drugs has not been well understood, although structural flexibility has been implicated. To gain insight into this transporter's broad substrate specificity and to assess its ability to accommodate a variety of molecular and structural changes, we generated human-mouse P-gp chimeras by the exchange of homologous transmembrane and nucleotide-binding domains. High-level expression of these chimeras by BacMam- and baculovirus-mediated transduction in mammalian (HeLa) and insect cells, respectively, was achieved. There were no detectable differences between wild-type and chimeric P-gp in terms of cell surface expression, ability to efflux the P-gp substrates rhodamine 123, calcein AM, and JC-1, or to be inhibited by the substrate cyclosporine A and the inhibitors tariquidar and elacridar. Additionally, expression of chimeric P-gp was able to confer a paclitaxel-resistant phenotype to HeLa cells characteristic of P-gp-mediated drug resistance. P-gp ATPase assays and photo-cross-linking with [(125)I]iodoarylazidoprazosin confirmed that transport and biochemical properties of P-gp chimeras were similar to those of wild-type P-gp, although differences in drug binding were detected when human and mouse transmembrane domains were combined. Overall, chimeras with one or two mouse P-gp domains were deemed functionally equivalent to human wild-type P-gp, demonstrating the ability of human P-gp to tolerate major structural changes. PMID- 26820616 TI - Effects of Preexcitation Syndrome on Terminal QRS Vector Observed in Spatial Vector. AB - BACKGROUND: Preexcitation syndrome could affect terminal QRS vector, which is not emphasized in clinic. In this study, we made a comparison between vectorcardiogram (VCG) before and after ablation to observe the change of terminal QRS vector. Furthermore, the relationship between the change of terminal QRS vector and accessory pathway (AP) as well as the change of initial QRS vector (delta vector) was analyzed. METHODS: Thirty patients who were proved to have a single AP by ablation were included. All patients were divided into seven groups based on the AP location. Comparison between VCG before and after ablation was made to observe the change of terminal and delta vector. The relationship between the change of terminal QRS vector and AP location as well as delta vector was analyzed. RESULTS: (1) All 30 patients had a change in terminal QRS vector (elevation and/or azimuth) in comparison to postablation VCG. (2) The change of terminal QRS vector was related to delta vector and AP location. The agreement and consistency between the change of terminal QRS vector and delta vector were 91.65% and 0.856 (P < 0.01), respectively. CONCLUSIONS: (1) Both initial and terminal QRS vector are affected by the antegrade conduction of AP. The change of terminal QRS vector is related to the AP location and delta vector. (2) The effect of preexcitation syndrome on QRS terminal vector is shown as more intuitive and easy in spatial vector by comparison with electrocardiogram, which is helpful for the diagnosis of atypical preexcitation and localization of AP. PMID- 26820617 TI - The Impact of Lowering Haemoglobin Targets on Patterns of Erythropoiesis Stimulating Agent Use in Patients on Haemodialysis. AB - BACKGROUND/AIMS: Haemoglobin (Hb) targets have been reduced in patients receiving haemodialysis (HD). We have investigated the impact of new guidance on current practices and costs. METHODS: Anaemia management in all patients undergoing thrice-weekly HD was retrospectively reviewed. Hb targets were compared against Kidney Disease: Improving Global Outcomes 2012 recommendations. The impact of new guidance was assessed by comparing anaemia parameters pre- and post-guideline publication. RESULTS: Two hundred and ninety two patients, with a mean age of 64 years were included. The Hb target range was achieved in 44% patients and was above target in 51%. In a sub-group of 230 patients, the mean Hb did not differ during Q4-2011 and Q4-2012. A reduction in erythropoiesis-stimulating agent (ESA) use was observed. ESA efficiency (Hb/ESA) increased in the later period (6.08 vs. 6.41 g/l/MUg) and was associated with a 3% cost reduction. CONCLUSION: Introduction of guidelines lowering Hb targets in HD patients led to more efficient ESA usage and cost-savings. Anaemia treatment, however, remains unnecessarily aggressive in some patients. Further reductions in Hb and ESA dose are achievable. PMID- 26820615 TI - AISF-SIMTI position paper: the appropriate use of albumin in patients with liver cirrhosis. AB - The use of human albumin is common in hepatology since international scientific societies support its administration to treat or prevent severe complications of cirrhosis, such as the prevention of post-paracentesis circulatory dysfunction after large-volume paracentesis and renal failure induced by spontaneous bacterial peritonitis, and the treatment of hepatorenal syndrome in association with vasoconstrictors. However, these indications are often disregarded, mainly because the high cost of human albumin leads health authorities and hospital administrations to restrict its use. On the other hand, physicians often prescribe human albumin in patients with advanced cirrhosis for indications that are not supported by solid scientific evidence and/or are still under investigation in clinical trials.In order to implement appropriate prescription of human albumin and to avoid its futile use, the Italian Association for the Study of the Liver (AISF) and the Italian Society of Transfusion Medicine and Immunohaematology (SIMTI) nominated a panel of experts, who reviewed the available clinical literature and produced practical clinical recommendations for the use of human albumin in patients with cirrhosis. PMID- 26820618 TI - Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Three-Year Results From the Randomized SCHEDULE Study. AB - In a randomized, open-label trial, de novo heart transplant recipients were randomized to everolimus (3-6 ng/mL) with reduced-exposure calcineurin inhibitor (CNI; cyclosporine) to weeks 7-11 after transplant, followed by increased everolimus exposure (target 6-10 ng/mL) with cyclosporine withdrawal or standard exposure cyclosporine. All patients received mycophenolate mofetil and corticosteroids. A total of 110 of 115 patients completed the 12-month study, and 102 attended a follow-up visit at month 36. Mean measured GFR (mGFR) at month 36 was 77.4 mL/min (standard deviation [SD] 20.2 mL/min) versus 59.2 mL/min (SD 17.4 mL/min) in the everolimus and CNI groups, respectively, a difference of 18.3 mL/min (95% CI 11.1-25.6 mL/min; p < 0.001) in the intention to treat population. Multivariate analysis showed treatment to be an independent determinant of mGFR at month 36. Coronary intravascular ultrasound at 36 months revealed significantly reduced progression of allograft vasculopathy in the everolimus group compared with the CNI group. Biopsy-proven acute rejection grade >=2R occurred in 10.2% and 5.9% of everolimus- and CNI-treated patients, respectively, during months 12-36. Serious adverse events occurred in 37.3% and 19.6% of everolimus- and CNI-treated patients, respectively (p = 0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte-depleting induction is safe at intermediate follow-up. This regimen, used selectively, may offer adequate immunosuppressive potency with a sustained renal advantage. PMID- 26820619 TI - Ultra-thin resin embedding method for scanning electron microscopy of individual cells on high and low aspect ratio 3D nanostructures. AB - The preparation of biological cells for either scanning or transmission electron microscopy requires a complex process of fixation, dehydration and drying. Critical point drying is commonly used for samples investigated with a scanning electron beam, whereas resin-infiltration is typically used for transmission electron microscopy. Critical point drying may cause cracks at the cellular surface and a sponge-like morphology of nondistinguishable intracellular compartments. Resin-infiltrated biological samples result in a solid block of resin, which can be further processed by mechanical sectioning, however that does not allow a top view examination of small cell-cell and cell-surface contacts. Here, we propose a method for removing resin excess on biological samples before effective polymerization. In this way the cells result to be embedded in an ultra thin layer of epoxy resin. This novel method highlights in contrast to standard methods the imaging of individual cells not only on nanostructured planar surfaces but also on topologically challenging substrates with high aspect ratio three-dimensional features by scanning electron microscopy. PMID- 26820621 TI - Albert J. Stunkard: His Research on Obesity and Its Psychological Impact. AB - Albert J. ("Mickey") Stunkard, MD, was a leader in the field of obesity research, with his work spanning more than five decades. He published several groundbreaking findings on the psychosocial influences of obesity, the genetics of obesity, and the relationship between obesity and factors such as socioeconomic status, stigma, and mood. He also helped establish two eating disorders associated with obesity-binge eating disorder and night eating syndrome. This paper highlights his work and its implications for the field. PMID- 26820620 TI - Common Variants in CLDN2 and MORC4 Genes Confer Disease Susceptibility in Patients with Chronic Pancreatitis. AB - A recent genome-wide association study (GWAS) identified association with variants in X-linked CLDN2 and MORC4, and PRSS1-PRSS2 loci with chronic pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62% and alcoholic in 16.38% of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525-OR 1.71, P = 1.38 x 10-09; rs12008279-OR 1.56, P = 1.53 x 10-04) and 2 variants in MORC4 gene (rs12688220-OR 1.72, P = 9.20 x 10-09; rs6622126-OR 1.75, P = 4.04x10-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10-06) and SAMD12-TNFRSF11B (OR 0.49, 95% CI [0.31 0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10 14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients. PMID- 26820622 TI - Impact of Perceived Healthiness of Food on Food Choices and Intake. AB - Healthy eating is an important determinant of health, but adherence to dietary guidelines remains a public health concern. Identifying factors that impact dietary habits is therefore important to facilitate healthy eating. One widely used strategy to help consumers make healthier food choices is nutrition information, such as labeling and claims. Despite the intention of these strategies to improve decision making, they can also be misunderstood or misinterpreted by consumers. The aim of this review is to explore food perceptions by examining how cognitive factors influence perceived healthiness of food, and the impact of perceived healthiness of food on food choices and intake. Overall findings of this review suggest that cognitive factors, such as type of food and branding, significantly contribute to judgmental bias and have an impact on perceived healthiness while not consistently or systematically influencing choice and intake. PMID- 26820623 TI - LDLR and PCSK9 Are Associated with the Presence of Antiphospholipid Antibodies and the Development of Thrombosis in aPLA Carriers. AB - INTRODUCTION: The identification of the genetic risk factors that could discriminate non- thrombotic from thrombotic antiphospholipid antibodies (aPLA) carriers will improve prognosis of these patients. Several human studies have shown the presence of aPLAs associated with atherosclerotic plaque, which is a known risk factor for thrombosis. Hence, in order to determine the implication of atherosclerosis in the risk of developing thrombosis in aPLA positive patients, we performed a genetic association study with 3 candidate genes, APOH, LDLR and PCSK9. MATERIAL & METHODS: For genetic association study we analyzed 190 aPLA carriers -100 with non-thrombotic events and 90 with thrombotic events- and 557 healthy controls. Analyses were performed by chi2 test and were corrected by false discovery rate. To evaluate the functional implication of the newly established susceptibility loci, we performed expression analyses in 86 aPLA carrier individuals (43 with thrombotic manifestations and 43 without it) and in 45 healthy controls. RESULTS: Our results revealed significant associations after correction in SNPs located in LDLR gene with aPLA carriers and thrombotic aPLA carriers, when compared with healthy controls. The most significant association in LDLR gene was found between SNP rs129083082 and aPLA carriers in recessive model (adjusted P-value = 2.55 x 10-3; OR = 2.18; 95%CI = 1.49-3.21). Furthermore, our work detected significant allelic association after correction between thrombotic aPLA carriers and healthy controls in SNP rs562556 located in PCSK9 gene (adjusted P-value = 1.03 x 10-2; OR = 1.60; 95%CI = 1.24-2.06). Expression level study showed significantly decreased expression level of LDLR gene in aPLA carriers (P-value <0.0001; 95%CI 0.16-2.10; SE 0.38-1.27) in comparison to the control group. DISCUSSION: Our work has identified LDLR gene as a new susceptibility gene associated with the development of thrombosis in aPLA carriers, describing for the first time the deregulation of LDLR expression in individuals with aPLAs. Besides, thrombotic aPLA carriers also showed significant association with PCSK9 gene, a regulator of LDLR plasma levels. These results highlight the importance of atherosclerotic processes in the development of thrombosis in patients with aPLA. PMID- 26820625 TI - Erratum to: Criteria of the German Society of Cardiology for the establishment of chest pain units: update 2015. PMID- 26820626 TI - Application of a Multiplex Quantitative PCR to Assess Prevalence and Intensity Of Intestinal Parasite Infections in a Controlled Clinical Trial. AB - BACKGROUND: Accurate quantitative assessment of infection with soil transmitted helminths and protozoa is key to the interpretation of epidemiologic studies of these parasites, as well as for monitoring large scale treatment efficacy and effectiveness studies. As morbidity and transmission of helminth infections are directly related to both the prevalence and intensity of infection, there is particular need for improved techniques for assessment of infection intensity for both purposes. The current study aimed to evaluate two multiplex PCR assays to determine prevalence and intensity of intestinal parasite infections, and compare them to standard microscopy. METHODOLOGY/PRINCIPAL FINDINGS: Faecal samples were collected from a total of 680 people, originating from rural communities in Timor Leste (467 samples) and Cambodia (213 samples). DNA was extracted from stool samples and subject to two multiplex real-time PCR reactions the first targeting: Necator americanus, Ancylostoma spp., Ascaris spp., and Trichuris trichiura; and the second Entamoeba histolytica, Cryptosporidium spp., Giardia. duodenalis, and Strongyloides stercoralis. Samples were also subject to sodium nitrate flotation for identification and quantification of STH eggs, and zinc sulphate centrifugal flotation for detection of protozoan parasites. Higher parasite prevalence was detected by multiplex PCR (hookworms 2.9 times higher, Ascaris 1.2, Giardia 1.6, along with superior polyparasitism detection with this effect magnified as the number of parasites present increased (one: 40.2% vs. 38.1%, two: 30.9% vs. 12.9%, three: 7.6% vs. 0.4%, four: 0.4% vs. 0%). Although, all STH positive samples were low intensity infections by microscopy as defined by WHO guidelines the DNA-load detected by multiplex PCR suggested higher intensity infections. CONCLUSIONS/SIGNIFICANCE: Multiplex PCR, in addition to superior sensitivity, enabled more accurate determination of infection intensity for Ascaris, hookworms and Giardia compared to microscopy, especially in samples exhibiting polyparasitism. The superior performance of multiplex PCR to detect polyparasitism and more accurately determine infection intensity suggests that it is a more appropriate technique for use in epidemiologic studies and for monitoring large-scale intervention trials. PMID- 26820627 TI - Ion Migration in Organometal Trihalide Perovskite and Its Impact on Photovoltaic Efficiency and Stability. AB - Organometal trihalide perovskites (OTPs) are emerging as very promising photovoltaic materials because the power conversion efficiency (PCE) of OTP solar cells quickly rises and now rivals with that of single crystal silicon solar cells after only five-years research. Their prospects to replace silicon photovoltaics to reduce the cost of renewable clean energy are boosted by the low temperature solution processing as well as the very low-cost raw materials and relative insensitivity to defects. The flexibility, semitransparency, and vivid colors of perovskite solar cells are attractive for niche applications such as built-in photovoltaics and portable lightweight chargers. However, the low stability of current hybrid perovskite solar cells remains a serious issue to be solved before their broad application. Among all those factors that affect the stability of perovskite solar cells, ion migration in OTPs may be intrinsic and cannot be taken away by device encapsulation. The presence of ion migration has received broad attention after the report of photocurrent hysteresis in OTP based solar cells. As suggested by much direct and indirect experimental evidence, the ion migration is speculated to be the origin or an important contributing factor for many observed unusual phenomenon in OTP materials and devices, such as current-voltage hysteresis, switchable photovoltaic effect, giant dielectric constant, diminished transistor behavior at room temperature, photoinduced phase separation, photoinduced self-poling effect, and electrical-field driven reversible conversion between lead iodide (PbI2) and methylammonium lead triiodide (MAPbI3). Undoubtedly thorough insight into the ion-migration mechanism is highly desired for the development of OTP based devices to improve intrinsic stability in the dark and under illumination. In this Account, we critically review the recent progress in understanding the fundamental science on ion migration in OTP based solar cells. We look into both theoretical and experiment advances in answering these basic questions: Does ion migration occur and cause the photocurrent hysteresis in perovskite solar cells? What are the migrating ion species? How do ions migrate? How does ion migration impact the device efficiency and stability? How can ion migration be mitigated or eliminated? We also raise some questions that need to be understood and addressed in the future. PMID- 26820624 TI - Development of Functional Microfold (M) Cells from Intestinal Stem Cells in Primary Human Enteroids. AB - BACKGROUND & AIMS: Intestinal microfold (M) cells are specialized epithelial cells that act as gatekeepers of luminal antigens in the intestinal tract. They play a critical role in the intestinal mucosal immune response through transport of viruses, bacteria and other particles and antigens across the epithelium to immune cells within Peyer's patch regions and other mucosal sites. Recent studies in mice have demonstrated that M cells are generated from Lgr5+ intestinal stem cells (ISCs), and that infection with Salmonella enterica serovar Typhimurium increases M cell formation. However, it is not known whether and how these findings apply to primary human small intestinal epithelium propagated in an in vitro setting. METHODS: Human intestinal crypts were grown as monolayers with growth factors and treated with recombinant RANKL, and assessed for mRNA transcripts, immunofluorescence and uptake of microparticles and S. Typhimurium. RESULTS: Functional M cells were generated by short-term culture of freshly isolated human intestinal crypts in a dose- and time-dependent fashion. RANKL stimulation of the monolayer cultures caused dramatic induction of the M cell specific markers, SPIB, and Glycoprotein-2 (GP2) in a process primed by canonical WNT signaling. Confocal microscopy demonstrated a pseudopod phenotype of GP2 positive M cells that preferentially take up microparticles. Furthermore, infection of the M cell-enriched cultures with the M cell-tropic enteric pathogen, S. Typhimurium, led to preferential association of the bacteria with M cells, particularly at lower inoculum sizes. Larger inocula caused rapid induction of M cells. CONCLUSIONS: Human intestinal crypts containing ISCs can be cultured and differentiate into an epithelial layer with functional M cells with characteristic morphological and functional properties. This study is the first to demonstrate that M cells can be induced to form from primary human intestinal epithelium, and that S. Typhimurium preferentially infect these cells in an in vitro setting. We anticipate that this model can be used to generate large numbers of M cells for further functional studies of these key cells of intestinal immune induction and their impact on controlling enteric pathogens and the intestinal microbiome. PMID- 26820628 TI - Genetic and clinical data reinforce the role of GAS6 and TAM receptors in liver fibrosis. PMID- 26820629 TI - Diagnostic criteria for hepatocellular carcinoma ?3 cm with hepatocyte-specific contrast-enhanced magnetic resonance imaging. AB - BACKGROUND & AIMS: Current diagnostic imaging criteria for hepatocellular carcinoma (HCC) are dedicated to imaging with nonspecific extracellular contrast agents. This study aimed to evaluate diagnostic criteria for HCC ?3 cm on magnetic resonance imaging (MRI) with a hepatocyte-specific contrast agent through an inception cohort study. METHODS: Of 291 patients with chronic liver disease and new nodules of 1-3 cm in diameter at surveillance ultrasonography, 295 solid nodules (194 HCCs, 98 benign nodules, and three other malignancies) in 198 patients with a confirmed final diagnosis or ?24 months follow-up were evaluated on gadoxetic acid-enhanced MRI. Through univariate and multivariate logistic regression analyses, various diagnostic criteria were developed by combining significant MRI findings for diagnosing HCC. The diagnostic performance of each criterion was compared with that of the European Association for the Study of the Liver (EASL) criteria. RESULTS: Four MRI findings (arterial-phase hyperintensity, transitional-phase hypointensity, hepatobiliary-phase hypointensity, and rim enhancement) were independently significant for diagnosis of HCC ?3 cm. For whole nodules, EASL criteria showed the best performance for diagnosing HCC (sensitivity, 83.5%; specificity, 81.2%). For nodules ?2 cm in diameter, a new criterion (arterial-phase hyperintensity and hepatobiliary-phase hypointensity) showed a significantly higher sensitivity than that of the EASL criteria (83.0% vs. 74.5%, p=0.008), without a significantly different specificity (76.7% vs. 81.1%, p=0.125). CONCLUSIONS: EASL criteria exhibit the best diagnostic performance for HCC ?3 cm on hepatocyte-specific contrast enhanced MRI. A newly identified criterion (arterial-phase hyperintensity and hepatobiliary-phase hypointensity) may increase the diagnostic sensitivity of small (?2 cm) HCC. PMID- 26820630 TI - Synthetic nanoparticles camouflaged with biomimetic erythrocyte membranes for reduced reticuloendothelial system uptake. AB - Suppression of the reticuloendothelial system (RES) uptake is one of the most challenging tasks in nanomedicine. Coating stratagems using polymers, such as poly(ethylene glycol) (PEG), have led to great success in this respect. Nevertheless, recent observations of immunological response toward these synthetic polymers have triggered a search for better alternatives. In this work, natural red blood cell (RBC) membranes are camouflaged on the surface of Fe3O4 nanoparticles for reducing the RES uptake. In vitro macrophage uptake, in vivo biodistribution and pharmacokinetic studies demonstrate that the RBC membrane is a superior alternative to the current gold standard PEG for nanoparticle 'stealth'. Furthermore, we systematically investigate the in vivo potential toxicity of RBC membrane-coated nanoparticles by blood biochemistry, whole blood panel examination and histology analysis based on animal models. The combination of synthetic nanoparticles and natural cell membranes embodies a novel and biomimetic nanomaterial design strategy and presents a compelling property of functional materials for a broad range of biomedical applications. PMID- 26820631 TI - The Influence of Prior Knowledge on Perception and Action: Relationships to Autistic Traits. AB - Autism is characterised by a range of perceptual and sensorimotor deficits, which might be related to abnormalities in how autistic individuals use prior knowledge. We investigated this proposition in a large non-clinical population in the context of the size-weight illusion, where individual's expectations about object weight influence their perceptions of heaviness and fingertip forces. Although there was no relationship between autistic traits and the magnitude of the illusion, we observed an inverse relationship between AQ scores and how expectations influenced initial fingertip force application. These findings provide a novel dissociation between how perceptual and sensorimotor processes are related to autistic traits, and suggest that, autistic traits might explain some of the variance surrounding how individuals grip and lift objects. PMID- 26820633 TI - Universal Autism Screening for Toddlers: Recommendations at Odds. PMID- 26820632 TI - Impaired Gas Exchange at Birth and Risk of Intellectual Disability and Autism: A Meta-analysis. AB - We conducted meta-analyses of 67 studies on the association between neonatal proxies of impaired gas exchange and intellectual disability (ID) or autism spectrum disorders (ASD). Neonatal acidosis was associated with an odds ratio (OR) of 3.55 [95 % confidence interval (95 % CI) 2.23-5.49] for ID and an OR of 1.10 (95 % CI 0.91-1.31) for ASD. Children with a 5-min Apgar score of <7 had an OR of 5.39 (95 % CI 3.84-7.55) for ID and an OR of 1.67 (95 % CI 1.34-2.09) for ASD. O2 treatment was associated with an OR of 4.32 (95 % CI 3.23-5.78) for ID and an OR of 2.02 (95 % CI 1.45 to 2.83) for ASD. Our meta-analysis demonstrates an increased risk of ID and (to a lesser extent) ASD in children with neonatal hypoxia. Moreover, our findings raise the possibility that concomitant ID might account for the observed association between the gas exchange proxies and ASD. PMID- 26820634 TI - Altered interferon-gamma response in patients with Q-fever fatigue syndrome. AB - OBJECTIVES: Whether immunological mechanisms underlie Q-fever fatigue syndrome (QFS) remains unclear. For acute Q-fever, the antigen-specific interferon-gamma (IFNgamma) response may be a useful tool for diagnosis, and the IFNgamma/interleukin(IL)-2 production ratio may be a marker for chronic Q-fever and treatment monitoring. Here we explored the specific IFNgamma production and IFNgamma/IL-2 ratio in QFS patients. METHODS: IFNgamma and IL-2 production were tested in ex-vivo stimulated whole blood of QFS patients (n = 20), and compared to those previously determined in seropositive controls (n = 135), and chronic Q fever patients (n = 28). Also, the correlation between patient characteristics and IFNgamma, IL-2, and IFNgamma/IL-2 ratio was determined. RESULTS: QFS patients were younger (p < 0.001), but gender distribution was similar to seropositive controls and chronic Q-fever patients. Coxiella burnetii Nine Mile stimulation revealed a higher IFNgamma production in QFS (median 319.5 pg/ml) than in seropositive controls (120 pg/ml, p < 0.01), but comparable to chronic Q-fever (2846 pg/ml). The IFNgamma/IL-2 ratio was similar to that in seropositive controls, but lower than in chronic Q-fever patients (p < 0.01). Symptom duration was positively correlated with IL-2 production, and negatively correlated with the IFNgamma/IL-2 ratio. CONCLUSIONS: These results point to an altered cell mediated immunity in QFS, and suggest a different immune response than in chronic Q-fever. PMID- 26820635 TI - Dinitrosyl iron complexes with thiol-containing ligands as a "working form" of endogenous nitric oxide. AB - The material presented herein is an overview of the results obtained by our research team during the many years' study of biological activities and occurrence of dinitrosyl iron complexes (DNIC) with thiol-containing ligands in human and animal organisms. With regard to their dose dependence and vast diversity of biological activities, DNIC are similar to the system of endogenous NO, one of the most universal regulators of biological processes. The role of biologically active components in DNIC is played by their iron-dinitrosyl fragments, [Fe(NO)2], endowed with the ability to generate neutral NO molecules and nitrosonium ions (NO(+)). Their release is effected by heme-and thiol containing proteins, which fulfill the function of biological targets and acceptors of NO and NO(+). Beneficial regulatory effects of DNIC on physiological and metabolic processes are numerous and diverse and include, among other things, lowering of arterial pressure and accelerated healing of skin wounds. In the course of fast decomposition of their Fe(NO)2 fragments (e.g., in the presence of iron chelators), DNIC produce adverse (cytotoxic) effects, which can best be exemplified by their ability to suppress the development of experimental endometriosis in animals. In animal tissues, DNIC with thiol-containing ligands are predominantly represented by the binuclear form, which, contrary to mononuclear DNIC detectable by the 2.03 signal, is EPR-silent. The ample body of evidence on biological activities and occurrence of DNIC gained so far clearly demonstrates that in human and animal organisms DNIC with thiol-containing ligands represent a "working form" of the system of endogenous NO responsible for its accumulation and stabilization in animal tissues as well as its further transfer to its biological targets. PMID- 26820636 TI - Interplay between serotonin and cannabinoid function in the amygdala in fear conditioning. AB - The possible interactions between the cannabinoid and serotonin systems in the regions of the brain involved in emotional learning and memory formation have been studied by some researchers. In view of the key role of the amygdala in the acquisition and expression of fear memory, we investigated the involvement of basolateral amygdala (BLA) serotonin 5-HT4 receptors in arachidonylcyclopropylamide (ACPA; selective CB1 cannabinoid receptor agonist) induced fear memory consolidation impairment. In our study, a context and tone fear conditioning apparatus was used for testing fear conditioning in adult male NMRI mice. The results showed that intraperitoneal administration of ACPA 0.5 or 0.05, 0.1 and 0.5mg/kg immediately after training decreased the percentage of freezing time in context or tone fear conditioning respectively, suggesting a context- or tone-dependent fear memory consolidation impairment. Post-training intra-BLA microinjections of RS67333, as 5-HT4 serotonin receptor agonist, at doses of 0.025 and 0.05 ug/mouse also impaired context or tone memory consolidation, while RS23597, as 5-HT4 serotonin receptor antagonist, did not produce a marked difference in both fear memories as compared with the control group. Moreover, a subthreshold dose of RS67333 did not alter ACPA response in both fear conditionings. Interestingly, a subthreshold dose of RS23597 potentiated or reversed ACPA response at the dose of 0.01 or 0.05 respectively. It is concluded that BLA serotonin 5-HT4 receptors are involved in tone-dependent fear memory consolidation impairment induced by CB1 activation using ACPA, suggesting a modulatory role for serotonin 5-HT4 receptor. PMID- 26820637 TI - Ictal electrographic pattern of focal subcortical seizures induced by sound in rats. AB - It is now recognized that both generalized and focal seizures may originate in subcortical structures. The well-known types of focal subcortically-driven seizures are gelastic seizures in patients with the hypothalamic hamartoma and sound-induced seizures in rodents with audiogenic epilepsy. The seizures are generated by subcortical intrinsically epileptogenic focus, the hamartoma in humans and the inferior colliculus (IC) in rodents. In patients with gelastic epilepsy additional seizure types may develop with time that are supposed to result from secondary epileptogenesis and spreading of epileptic discharges to the cortex. Repeated audiogenic seizures can also lead to development of additional seizure behavior and secondary epileptic activation of the cortex. This process, named audiogenic kindling, may be useful for studying secondary subcortico-cortical epileptogenesis. Using intracollicular and intracortical recordings, we studied an ictal electrographic pattern of focal subcortical seizures induced by repeated sound stimulation in Wistar audiogenic-susceptible rats. The audiogenic seizures, representing brief attacks of paroxysmal unidirectional running, were accompanied by epileptiform abnormalities in the IC, mostly on the side ipsilateral to run direction, and enhanced rhythmic 8-9Hz activity in the cortex. With repetition of the subcortical seizures and kindling development, a secondary cortical discharge began to follow the IC seizure. The secondary discharge initially involved the cortex homolateral to the side of dominant subcortical epileptiform abnormalities and behaviorally expressed as limbic (partial) clonus. Kindling progression was associated with bilateralization of the secondary cortical discharge, an increase in its amplitude and duration, intensification of associated behavioral seizures (from partial clonus to generalized tonic-clonic convulsions). Thus, ictal recordings during brief audiogenic running seizures showed their focal subcortical origin. Repetition of the subcortical seizures may result in secondary subcortico cortical epileptogenesis manifested by emergence and progressive intensification of epileptiform discharges in the cortex. PMID- 26820638 TI - Hearing subject's own name induces the late positive component of event-related potential and beta power suppression. AB - The neuronal response to hearing a subject's own name (SON) has been often investigated using event-related potential (ERP) or time-frequency analysis, but seldom by a combination of these methods. Using this combination of approaches would allow the relationship between memory processes engaged by SON and the neuronal responses to be studied in more detail. Thus, the present study used both ERP and time-frequency analysis to investigate memory process for SON by comparing the responses to SON and to unfamiliar names. Specifically, the SON condition was compared with two control conditions: repeated unfamiliar names and singly presented unfamiliar names. This experimental design allowed us to determine the differences in memory processes between hearing one's own name and hearing unrelated but repeatedly heard names. ERP analysis showed that SON elicited a late positive component in parietal areas, while unfamiliar names elicited no positivity. Beta power suppression was observed in response to SON at 0.4-0.6s after stimulus onset at right central sites, but not in response to unfamiliar names. These results are indicative of an involvement of episodic memory processes on hearing SON, which corresponds to the recognition of one's own name. Further, the ERP results suggest the presence of a "new" stimulus recognition process that is activated by singly presented unfamiliar names but not by repeated unfamiliar names. PMID- 26820639 TI - Layer- and area-specific actions of norepinephrine on cortical synaptic transmission. AB - The cerebral cortex is a critical target of the central noradrenergic system. The importance of norepinephrine (NE) in the regulation of cortical activity is underscored by clinical findings that involve this catecholamine and its receptor subtypes in the regulation of a large number of emotional and cognitive functions and illnesses. In this review, we highlight diverse effects of the LC/NE system in the mammalian cortex. Indeed, electrophysiological, pharmacological, and behavioral studies in the last few decades reveal that NE elicits a mixed repertoire of excitatory, inhibitory, and biphasic effects on the firing activity and transmitter release of cortical neurons. At the intrinsic cellular level, NE can produce a series of effects similar to those elicited by other monoamines or acetylcholine, associated with systemic arousal. At the synaptic level, NE induces numerous acute changes in synaptic function, and 'gates' the induction of long-term plasticity of glutamatergic synapses, consisting in an enhancement of engaged and relevant cortical synapses and/or depression of unengaged synapses. Equally important in shaping cortical function, in many cortical areas NE promotes a characteristic, most often reversible, increase in the gain of local inhibitory synapses, whose extent and temporal properties vary between different areas and sometimes even between cortical layers of the same area. While we are still a long way from a comprehensive theory of the function of the LC/NE system, its cellular, synaptic, and plastic effects are consistent with the hypothesis that noradrenergic modulation is critical in coordinating the activity of cortical and subcortical circuits for the integration of sensory activity and working memory. This article is part of a Special Issue entitled SI: Noradrenergic System. PMID- 26820640 TI - Effects of an amyloid-beta 1-42 oligomers antibody screened from a phage display library in APP/PS1 transgenic mice. AB - We screened anti-Abeta1-42 antibodies from a human Alzheimer's disease (AD) specific single chain variable fragment (scFv) phage display library and assessed their effects in APP/PS1 transgenic mice. Reverse transcription-PCR was used to construct the scFv phage display library, and screening identified 11A5 as an anti-Abeta1-42 antibody. We mixed 11A5 and the monoclonal antibody 6E10 with Abeta1-42 and administered the mixture to Sprague-Dawley rats via intracerebroventricular injection. After 30 days, rats injected with the antibody/Abeta1-42 mixture and those injected with Abeta1-42 alone were tested on the Morris water maze. We also injected 11A5 and 6E10 into APP/PS1 transgenic mice and assessed the concentrations of Abeta in brain and peripheral blood by ELISA at 1-month intervals for 3 months. Finally we evaluated behavior changes in the Morris water maze. Rats injected with Abeta1-42 and mixed antibodies showed better performance in the Morris water maze than did rats injected with Abeta1-42 alone. In APP/PS1 transgenic mice, Abeta concentration was lower in the brains of the antibody-treated group than in the control group, but higher in the peripheral blood. The antibody-treated mice also exhibited improved behavioral performance in the Morris water maze. In conclusion, anti-Abeta1-42 antibodies (11A5) screened from the human scFv antibody phage display library promoted the efflux or clearance of Abeta1-42 and effectively decreased the cerebral Abeta burden in an AD mouse model. PMID- 26820642 TI - Modifications of the chemical structure of phenolics differentially affect physiological activities in pulvinar cells of Mimosa pudica L. II. Influence of various molecular properties in relation to membrane transport. AB - Early prediction of compound absorption by cells is of considerable importance in the building of an integrated scheme describing the impact of a compound on intracellular biological processes. In this scope, we study the structure activity relationships of several benzoic acid-related phenolics which are involved in many plant biological phenomena (growth, flowering, allelopathy, defense processes). Using the partial least squares (PLS) regression method, the impact of molecular descriptors that have been shown to play an important role concerning the uptake of pharmacologically active compounds by animal cells was analyzed in terms of the modification of membrane potential, variations in proton flux, and inhibition of the osmocontractile reaction of pulvinar cells of Mimosa pudica leaves. The hydrogen bond donors (HBD) and hydrogen bond acceptors (HBA), polar surface area (PSA), halogen ratio (Hal ratio), number of rotatable bonds (FRB), molar volume (MV), molecular weight (MW), and molar refractivity (MR) were considered in addition to two physicochemical properties (logD and the amount of non-dissociated form in relation to pKa). HBD + HBA and PSA predominantly impacted the three biological processes compared to the other descriptors. The coefficient of determination in the quantitative structure-activity relationship (QSAR) models indicated that a major part of the observed seismonasty inhibition and proton flux modification can be explained by the impact of these descriptors, whereas this was not the case for membrane potential variations. These results indicate that the transmembrane transport of the compounds is a predominant component. An increasing number of implicated descriptors as the biological processes become more complex may reflect their impacts on an increasing number of sites in the cell. The determination of the most efficient effectors may lead to a practical use to improve drugs in the control of microbial attacks on plants. PMID- 26820641 TI - Specificity and impact of adrenergic projections to the midbrain dopamine system. AB - Dopamine (DA) is a neuromodulator that regulates different brain circuits involved in cognitive functions, motor coordination, and emotions. Dysregulation of DA is associated with many neurological and psychiatric disorders such as Parkinson's disease and substance abuse. Several lines of research have shown that the midbrain DA system is regulated by the central adrenergic system. This review focuses on adrenergic interactions with midbrain DA neurons. It discusses the current neuroanatomy including source of adrenergic innervation, type of synapses, and adrenoceptors expression. It also discusses adrenergic regulation of DA cell activity and neurotransmitter release. Finally, it reviews several neurological and psychiatric disorders where changes in adrenergic system are associated with dysregulation of the midbrain DA system. This article is part of a Special Issue entitled SI: Noradrenergic System. PMID- 26820643 TI - Kinetic study of the anaerobic biodegradation of alkyl polyglucosides and the influence of their structural parameters. AB - This paper reports a study of the anaerobic biodegradation of non-ionic surfactants alkyl polyglucosides applying the method by measurement of the biogas production in digested sludge. Three alkyl polyglucosides with different length alkyl chain and degree of polymerization of the glucose units were tested. The influence of their structural parameters was evaluated, and the characteristics parameters of the anaerobic biodegradation were determined. Results show that alkyl polyglucosides, at the standard initial concentration of 100 mgC L(-1), are not completely biodegradable in anaerobic conditions because they inhibit the biogas production. The alkyl polyglucoside having the shortest alkyl chain showed the fastest biodegradability and reached the higher percentage of final mineralization. The anaerobic process was well adjusted to a pseudo first-order equation using the carbon produced as gas during the test; also, kinetics parameters and a global rate constant for all the involved metabolic process were determined. This modeling is helpful to evaluate the biodegradation or the persistence of alkyl polyglucosides under anaerobic conditions in the environment and in the wastewater treatment. PMID- 26820644 TI - Endogenous and exogenous sex steroid hormones in asthma and allergy in females: protocol for a systematic review and meta-analysis. PMID- 26820645 TI - Ten Simple Rules for a Bioinformatics Journal Club. PMID- 26820646 TI - Selection of the Maximum Spatial Cluster Size of the Spatial Scan Statistic by Using the Maximum Clustering Set-Proportion Statistic. AB - Spatial scan statistics are widely used in various fields. The performance of these statistics is influenced by parameters, such as maximum spatial cluster size, and can be improved by parameter selection using performance measures. Current performance measures are based on the presence of clusters and are thus inapplicable to data sets without known clusters. In this work, we propose a novel overall performance measure called maximum clustering set-proportion (MCS P), which is based on the likelihood of the union of detected clusters and the applied dataset. MCS-P was compared with existing performance measures in a simulation study to select the maximum spatial cluster size. Results of other performance measures, such as sensitivity and misclassification, suggest that the spatial scan statistic achieves accurate results in most scenarios with the maximum spatial cluster sizes selected using MCS-P. Given that previously known clusters are not required in the proposed strategy, selection of the optimal maximum cluster size with MCS-P can improve the performance of the scan statistic in applications without identified clusters. PMID- 26820647 TI - Molecular Genetics External Quality Assessment Pilot Scheme for Irinotecan Related UGT1A1 Genotyping in China. AB - Irinotecan is widely used in the treatment of solid tumors, especially in colorectal cancer and lung cancer. Molecular testing for UGT1A1 genotyping is increasingly required in China for optimum irinotecan administration. In order to determine the performance of laboratories with regard to the whole testing process for UGT1A1 to ensure the consistency and accuracy of the test results, the National Center for Clinical Laboratories conducted an external quality assessment program for UGT1A1*28 genotyping in 2015. The panel, which comprised of four known mutational samples and six wild-type samples, was distributed to 45 laboratories that test for the presence of UGT1A1*28 polymorphisms. Participating laboratories were allowed to perform polymorphism analysis by using their routine methods. The accuracy of the genotyping and reporting of results was analyzed. Other information from the individual laboratories, including the number of samples tested each month, accreditation/certification status, and test methodology, was reviewed. Forty-four of the 45 participants reported the correct results for all samples. There was only one genotyping error, with a corresponding analytical sensitivity of 99.44% (179/180 challenges; 95% confidence interval: 96.94-99.99%) and an analytical specificity of 100% (270/270 challenges; 95% confidence interval: 98.64-100%). Both commercial kits and laboratory development tests were commonly used by the laboratories, and pyrosequencing was the main methodology used (n = 26, 57.8%). The style of the written reports showed large variation, and many reports showed a shortage of information. In summary, the first UGT1A1 genotyping external quality assessment result demonstrated that UGT1A1 genotype analysis of good quality was performed in the majority of pharmacogenetic testing centers that were investigated. However, greater education on the reporting of UGT1A1 genetic testing results is needed. PMID- 26820648 TI - Unsupervised self-care predicts conduct problems: The moderating roles of hostile aggression and gender. AB - Despite widespread speculation about the detrimental effect of unsupervised self care on adolescent outcomes, little is known about which children are particularly prone to problem behaviors when left at home without adult supervision. The present research used data from a longitudinal study of 674 Mexican-origin children residing in the United States to examine the prospective effect of unsupervised self-care on conduct problems, and the moderating roles of hostile aggression and gender. Results showed that unsupervised self-care was related to increases over time in conduct problems such as lying, stealing, and bullying. However, unsupervised self-care only led to conduct problems for boys and for children with an aggressive temperament. The main and interactive effects held for both mother-reported and observational-rated hostile aggression and after controlling for potential confounds. PMID- 26820649 TI - Comparative evaluation of antibody detection tests to facilitate the diagnosis of multibacillary leprosy. AB - Despite control efforts, leprosy persists as a significant health concern in many regions. Diagnosis is achieved by a combination of clinical, histopathological, and bacteriological examinations, each of which presents a barrier to expeditious diagnosis, particularly by non-experts. Immunological investigations in research laboratories have clearly indicated that antibody detection tests could aid the diagnosis of leprosy. In this study, we detected circulating antibodies with two rapid diagnostic tests (RDT) involving immunochromatographic lateral flow platforms and one rapid ELISA system. Leprosy patients were identified with a high degree of sensitivity in each assay (over 80% in all; over 90% among cases with bacterial indices >1+), although critical differences were observed in specificity. While the specificity of CTK OnSite Leprosy Ab Rapid Test and InBios Leprosy DetectTM fast ELISA were high (96.4 and 93.7% in the general population, respectively), there was a marked reduction in OrangeLife NDO-LID(r) RDT (only 25.0%). As anticipated, seropositivity rates were marginally higher in contacts of leprosy patients than in endemic controls. Although we observed a slight drop in test band intensity when blood, rather than serum, was used to develop OnSite Leprosy Ab Rapid Tests, the sensitivity and specificity of these tests was unaffected. When we contrasted test performance with clinical and bacteriological information, we found that RDT and ELISA results positively correlated with the bacteriological index. These data indicate that these assays could be a ready replacement of invasive, insensitive, and time consuming skin slit smear procedures that additionally require expert microscopic examinations. We propose that, due to their speed and point of care applicability, the RDT could be used as an initial entry point to the diagnostic protocols, with confirmation of results attained in a highly quantitative manner following serum transfer to a reference laboratory. PMID- 26820650 TI - Implication of sortase-dependent proteins of Streptococcus thermophilus in adhesion to human intestinal epithelial cell lines and bile salt tolerance. AB - Streptococcus thermophilus (ST) is a lactic acid bacterium widely used in dairy industry and displays several properties which could be beneficial for host. The objective of this study was to investigate, in vitro, the implication of sortase A (SrtA) and sortase-dependent proteins (SDPs) in the adhesion of ST LMD-9 strain to intestinal epithelial cells (IECs) and resistance to bile salt mixture (BSM; taurocholoate, deoxycholate, and cholate). The effect of mutations in prtS (protease), mucBP (MUCin-Binding Protein), and srtA genes in ST LMD-9 in these mechanisms were examined. The HT29-MTX, HT29-CL.16E, and Caco-2 TC7 cell lines were used. HT29-MTX and HT29-CL.16E cells express different mucins found in the gastro intestinal tract; whereas, Caco-2 TC7 express cell surface proteins found in the small intestine. All mutants showed different adhesion profiles depending on cell lines. The mutation in genes srtA and mucBP leads to a significant decrease in LMD-9 adhesion capacity to Caco-2 TC7 cells. A mutation in mucBP gene has also shown a significant decrease in LMD-9 adhesion capacity to HT29-CL.16E cells. However, no difference was observed using HT29-MTX cells. Furthermore, ST LMD-9 and srtA mutant were resistant to BSM up to 3 mM. Contrariwise, no viable bacteria were detected for prtS and mucBP mutants at this concentration. Two conclusions could be drawn. First, SDPs could be involved in the LMD-9 adhesion depending on the cell lines indicating the importance of eukaryotic-cell surface components in adherence. Second, SDPs could contribute to resistance to bile salts probably by maintaining the cell membrane integrity. PMID- 26820651 TI - At-line determination of spore inoculum quality in Penicillium chrysogenum bioprocesses. AB - Spore inoculum quality in filamentous bioprocesses is a critical parameter influencing pellet morphology and, consequently, process performance. It is essential to determine the concentration of viable spores before inoculation, to implement quality control and decrease batch-to-batch variability. The ability to assess the spore physiologic status with close-to-real time resolution would offer interesting perspectives enhanced process analytical technology (PAT) and quality by design (QbD) strategies. Up to now, the parameters contributing to spore inoculum quality are not clearly defined. The state-of-the-art method to investigate this variable is colony-forming unit (CFU) determination, which assesses the number of growing spores. This procedure is tedious, associated with significant inherent bias, and not applicable in real time.Here, a novel method is presented, based on the combination of viability staining (propidium iodide and fluorescein diacetate) and large-particle flow cytometry. It is compatible with the complex medium background often observed in filamentous bioprocesses and allows for a classification of the spores into different subpopulations. Next to viable spores with intact growth potential, dormant or inactive as well as physiologically compromised cells are accurately determined. Hence, a more holistic few on spore inoculum quality and early-phase biomass composition is provided, offering enhanced information content.In an industrially relevant model bioprocess, good correlation to CFU counts was found. Morphological parameters (e.g. spore swelling) that are not accessible via standard monitoring tools were followed over the initial process phase with close temporal resolution. PMID- 26820652 TI - Discordant assessment of tumor biomarkers by histopathological and molecular assays in the EORTC randomized controlled 10041/BIG 03-04 MINDACT trial breast cancer : Intratumoral heterogeneity and DCIS or normal tissue components are unlikely to be the cause of discordance. AB - Accurate identification of breast cancer patients most likely to benefit from adjuvant systemic therapies is crucial. Better understanding of differences between methods can lead to an improved ER, PgR, and HER-2 assessment. The purpose of this preplanned translational research is to investigate the correlation of central IHC/FISH assessments with microarray mRNA readouts of ER, PgR, and HER-2 status in the MINDACT trial and to determine if any discordance could be attributed to intratumoral heterogeneity or the DCIS and normal tissue components in the specimens. MINDACT is an international, prospective, randomized, phase III trial investigating the clinical utility of MammaPrint in selecting patients with early breast cancer for adjuvant chemotherapy (n = 6694 patients). Gene-expression data were obtained by TargetPrint; IHC and/or FISH were assessed centrally (n = 5788; 86 %). Macroscopic and microscopic evaluation of centrally submitted FFPE blocks identified 1427 cases for which the very same sample was submitted for gene-expression analysis. TargetPrint ER had a positive agreement of 98 %, and a negative agreement of 95 % with central pathology. Corresponding figures for PgR were 85 and 94 % and for HER-2 72 and 99 %. Agreement of mRNA versus central protein was not different when the same or a different portion of the tumor tissue was analyzed or when DCIS and/or normal tissue was included in the sample subjected to mRNA assays. This is the first large analysis to assess the discordance rate between protein and mRNA analysis of breast cancer markers, and to look into intratumoral heterogeneity, DCIS, or normal tissue components as a potential cause of discordance. The observed difference between mRNA and protein assessment for PgR and HER-2 needs further research; the present analysis does not support intratumoral heterogeneity or the DCIS and normal tissue components being likely causes of the discordance. PMID- 26820653 TI - The effect of resistance training on markers of immune function and inflammation in previously sedentary women recovering from breast cancer: a randomized controlled trial. AB - The purpose of this randomized controlled trial was to determine the effects of resistance training (RT) on markers of inflammation and immune function in breast cancer survivors. Thirty-nine breast cancer survivors were randomly assigned to a RT (n = 20) or control (n = 19) group. RT performed supervized exercise three times per week. Natural killer cell (NK) and natural killer T-cell (NKT) function, and markers of inflammation (serum TNF-alpha, IL-6, IL-10, and CRP) were measured before and after training. Changes in NK and NKT cell function were analyzed using ANCOVA, with the change score the dependent variable, and the baseline value of the same variable the covariate. Effect sizes (ES) were calculated via partial eta-squared. We found a significant reduction, and large associated ESs, in the RT group compared to the control group for change in NK cell expression of TNF-alpha (p = 0.005, ES = 0.21) and NKT cell expression of TNF-alpha (p = 0.04, ES = 0.12). No differences were observed in any serum marker. Significant improvements in all measurements of strength were found in RT compared to control (p < 0.001; large ESs ranging from 0.32 to 0.51). These data demonstrate that RT has a beneficial effect on the NK and NKT cell expression of TNF-alpha indicating that RT may be beneficial in improving the inflammatory profile in breast cancer survivors. PMID- 26820654 TI - Infection Prevention in Transplantation. AB - The number of patients undergoing hematopoietic cell and solid organ transplantation are increasing every year, as are the number of centers both transplanting and caring for these patients. Improvements in transplant procedures, immunosuppressive regimens, and prevention of transplant-associated complications have led to marked improvements in survival in both populations. Infections remain one of the most important sources of excess morbidity and mortality in transplant, and therefore, infection prevention strategies are a critical element for avoiding these complications in centers caring for high-risk patients. This manuscript aims to provide an update of recent data on prevention of major healthcare-associated infections unique to transplantation, reviews the emergence of antimicrobial resistant infections, and discusses updated strategies to both identify and prevent transmission of these pathogens in transplant recipients. PMID- 26820655 TI - Magnetic resonance parkinsonism index in progressive supranuclear palsy and vascular parkinsonism. AB - To investigate accuracy of the magnetic resonance parkinsonism index (MRPI) in differentiating progressive supranuclear palsy (PSP) from vascular parkinsonism (VP). We retrospectively analyzed radiological data of 12 PSP patients and 17 VP patients group-matched by age and sex who performed a standardized brain magnetic resonance imaging (MRI). Analysis of selected structures morphometry was performed to all study subjects and the MRPI was calculated for each selected patient. MRI midbrain area as well as superior cerebellar peduncle width were significantly lower in PSP patients compared to VP subjects. MRPI was significantly larger in PSP patients compared to VP subjects. MRPI value >=13 distinguished the two groups with a sensitivity of 100 % (95 % CI 69.9-100) and a specificity of 100 % (95 % CI 77.1-100). MRPI may represent an accurate tool in differentiating PSP from VP. PMID- 26820656 TI - [A multicentric, randomized, double-blind, placebo-controlled Phase III study of ARN-509 in men with non-metastatic (M0) castration-resistant prostate cancer (SPARTAN): AUO study AP 82/14]. PMID- 26820658 TI - [Current Practice in the Transurethral Treatment of Benign Prostatic Obstruction under Oral Anticoagulants : A Nation-wide Survey]. AB - BACKROUND: Only few studies have assessed the safety and efficacy of transurethral surgery (TS) for the treatment of benign prostatic obstruction (BPO) in patients on oral anticoagulants. The aim of our study was to evaluate current treatment strategies and complication rates of TS for the treatment of BPO in patients on OA using an online survey. MATERIALS AND METHODS: A total of 300 German departments of urology received an e-mail with a link for the online survey. The items of the questionnaire assessed the present practice of TS for BPO in patients on OA and the occurrence of complications. RESULTS: Seventy-five (23.4 %) departments responded to the online questionnaire. Of the respondents, 94.7 % performed TS in patients with BPO on OA and 42.7 % answered that they perform more than 30 prostate surgeries per year under OA. The respondents indicated that surgeries were carried out under aspirin (96 %), clopidogrel (46.7 %) or phenprocoumon (26.7 %). Indications for surgeries under OA were made by cardiologist recommendation (82.7 %), the surgeon (37.3 %), a need for emergency surgery (52 %), or the patient's will (10.7 %). Sixty-two (82.7 %) of the respondents perform bipolar or monopolar transurethral resection of the prostate (TUR-P) in patients on OA. In addition, 69.3 % of the respondents indicated that they use laser prostatectomy in patients on OA (thulium 24 %, Greenlight 24 %, holmium 16 %, and diode laser 5.3 %). Cardiovascular complications occurred in 12 % of the respondents. CONCLUSIONS: Despite the poor evidence for performing TS of BPO under OA, our survey showed surprising results: TS of BPO under OA is frequently performed, especially bipolar and monopolar TUR-P. Although our data were obtained using an online survey, the complication rates appear to be lower than previously thought. PMID- 26820659 TI - [Postchemotherapy residual tumour resection in complex metastatic sites of advanced testicular germ cell tumours]. AB - INTRODUCTION: Postchemotherapy residual tumour resection (PC-RTR) is an integral part of the multimodal therapy for advanced testicular germ cell tumours. Depending on the extent and localisation of the residual mass, PC-RTR may necessitate a multidisciplinary procedure (which should be planned preoperatively), to resolve even complex situations in an oncologically sound manner, with lower treatment-related morbidity The aim of article is to report on the interdisciplinary management of complex residual masses. PATIENTS AND METHODS: Of a total of 162 patients who underwent PC-RTR, 24 (17.8 %) patients underwent, in addition to a bilateral postchemotherapy retroperitoneal lymphadenectomy (PC-RPLND), complex adjunctive resections including the abdominal aorta, the inferior vena cava, or the thoracic/lumbar spine, and the neighbouring vessels (n = 15). We performed a retrospective analysis of treatment-associated complications according to the Clavien-Dindo classification and of progression free, cancer-specific and overall survival. RESULTS: Median patient age was 24.5 (18-52) years. All patients had an intermediate or poor prognosis according to the International Germ Cell Cancer Collaboration Group (IGCCCG). Median tumour diameter at the time of surgery was 18.6 (9.0-35) cm. In 5 patients 1-2 metastatic lumbar vertebral bodies were completely resected, stabilised and replaced by means of a cage. In 6 patients resection of the abdominal aorta/inferior vena cava with vascular prosthesis replacement was required owing to infiltration. In 2 patients the common iliac artery or vein was resected and replaced. In addition, retrocrural lymph nodes had to be resected in 5 patients and 3 patients required adjunctive nephrectomy. In another 4 patients the Whipple procedure was required owing to infiltration into the pancreas and/or duodenum. The median operating time was 7.8 (6-15) h, the median blood loss was around 1,450 (900-3,400) ml, and 2 Clavien-Dindo grade IVa complications occurred. Pathohistology revealed teratoma/vital cancer in 16/24 patients and scarring/necrosis in 8 patients. After a median follow-up of 2.5 years, 1 patient developed recurrent disease and 1 patient died of the disease. CONCLUSIONS: Postchemotherapy, a few patients with advanced nonseminomas (NS) need complex residual tumour resection in an interdisciplinary setting, with a good functional and oncological outcome. Even the involvement of vascular vertebral structures does not constitute a contraindication for complete resection. PMID- 26820660 TI - [Advanced Prostate Cancer Consensus Conference (APCCC) 2015 in St. Gallen : Critical review of the recommendations on diagnosis and therapy of metastatic prostate cancer by a German expert panel]. AB - In March 2015, the first Advanced Prostate Cancer Consensus Conference (APCC) took place in St. Gallen. 41 experts from 17 countries reviewed important areas of controversy in advanced hormone-naive and castration-resistant prostate cancer and gave therapy recommendations. These results have been recently published in "Annals of Oncology". While most of the recommendations from St. Gallen are comprehensible, some of them need to be further discussed. Therefore, we as a German expert panel will critically debate the St. Gallen recommendations. For metastatic hormone-naive prostate cancer, continuous androgen deprivation remains the standard. There is no evidence for superiority of primary maximal androgen deprivation. Patients suitable for chemotherapy, especially in the presence of high tumour burden, should receive androgen deprivation plus taxanes upfront. In metastatic castration resistant prostate cancer, novel hormonal agents like abiraterone or enzalutamid should be the treatment of choice in the majority of patients. Taxanes should be used first-line in patients with unfavourable prognostic markers. Radium-223 is an option in symptomatic patients with bone metastases. There is first evidence that second-line hormonal treatment after first-line failure of a novel endocrine agent has a high failure rate. Cabazitaxel should be part of the treatment sequence in patients with a good performance status. Baseline staging for castration-resistant prostate cancer should include CT-abdomen/-chest and bone scan. Radiographic monitoring should be performed 2 to 3 times a year. Determination of PSA and ALP is to take place every 2 to 4 months. PMID- 26820661 TI - [Wearable Technologies for Urologists]. PMID- 26820662 TI - Activating protein phosphatase 2A (PP2A) enhances tristetraprolin (TTP) anti inflammatory function in A549 lung epithelial cells. AB - Chronic respiratory diseases are driven by inflammation, but some clinical conditions (severe asthma, COPD) are refractory to conventional anti-inflammatory therapies. Thus, novel anti-inflammatory strategies are necessary. The mRNA destabilizing protein, tristetraprolin (TTP), is an anti-inflammatory molecule that functions to induce mRNA decay of cytokines that drive pathogenesis of respiratory disorders. TTP is regulated by phosphorylation and protein phosphatase 2A (PP2A) is responsible for dephosphorylating (and hence activating) TTP, amongst other targets. PP2A is activated by small molecules, FTY720 and AAL(S), and in this study we examine whether these compounds repress cytokine production in a cellular model of airway inflammation using A549 lung epithelial cells stimulated with tumor necrosis factor alpha (TNFalpha) in vitro. PP2A activators significantly increase TNFalpha-induced PP2A activity and inhibit mRNA expression and protein secretion of interleukin 8 (IL-8) and IL-6; two key pro inflammatory cytokines implicated in respiratory disease and TTP targets. The effect of PP2A activators is not via an increase in TNFalpha-induced TTP mRNA expression; instead we demonstrate a link between PP2A activation and TTP anti inflammatory function by showing that specific knockdown of TTP with siRNA reversed the repression of TNFalpha-induced IL-8 and IL-6 mRNA expression and protein secretion by FTY720. Therefore we propose that PP2A activators affect the dynamic equilibrium regulating TTP; shifting the equilibrium from phosphorylated (inactive) towards unphosphorylated (active) but unstable TTP. PP2A activators boost the anti-inflammatory function of TTP and have implications for future pharmacotherapeutic strategies to combat inflammation in respiratory disease. PMID- 26820663 TI - Erratum to: Steroid-resistant nephrotic syndrome in a child with dysmorphic features: Answers. PMID- 26820664 TI - Why governance? A challenge to good governance of biobanks. AB - In this commentary on Karla Stroud and Kieran O'Doherty's 'Ethically Sustainable Governance in the Biobanking of Eggs and Embryos for Research' (2015) I call into question the need for good governance to overcome the challenges facing biobanking of eggs and embryos. I argue that the principles of good governance for biobanking that Stroud and O'Doherty outline come up short in providing concrete normative guidance to resolve the challenges associated with a biobank for eggs and embryos. PMID- 26820666 TI - Prevalence of Dystonia in Antioquia, Colombia. AB - BACKGROUND: There are few published epidemiological studies concerning dystonia. Its true prevalence has been difficult to establish. There is no data published in Latin America on this matter. METHODS: In this study the prevalence of dystonias in the Department of Antioquia (Colombia) was estimated using a capture recapture methodology with log-linear modeling, including cases in 3 centers for neurological referrals that cover the Department of Antioquia from 2007 to 2012. RESULTS: The overall prevalence was 712 per 1,000,000 (95% CI 487-937). Of the total of 874 patients, 79% had primary dystonias, and 75.5% had focal dystonias. The delay in diagnosis was longer for primary dystonias, with a median of 1 year. CONCLUSION: We found a high prevalence of dystonias in Antioquia. The frequency of the different types of dystonias, as well as the demographic characteristics of our patients, is similar to data from other populations of the world. PMID- 26820665 TI - Singaporean Mothers' Perception of Their Three-year-old Child's Weight Status: A Cross-Sectional Study. AB - OBJECTIVE: Inaccurate parental perception of their child's weight status is commonly reported in Western countries. It is unclear whether similar misperception exists in Asian populations. This study aimed to evaluate the ability of Singaporean mothers to accurately describe their three-year-old child's weight status verbally and visually. METHODS: At three years post delivery, weight and height of the children were measured. Body mass index (BMI) was calculated and converted into actual weight status using International Obesity Task Force criteria. The mothers were blinded to their child's measurements and asked to verbally and visually describe what they perceived was their child's actual weight status. Agreement between actual and described weight status was assessed using Cohen's Kappa statistic (kappa). RESULTS: Of 1237 recruited participants, 66.4% (n = 821) with complete data on mothers' verbal and visual perceptions and children's anthropometric measurements were analysed. Nearly thirty percent of the mothers were unable to describe their child's weight status accurately. In verbal description, 17.9% under-estimated and 11.8% over estimated their child's weight status. In visual description, 10.4% under estimated and 19.6% over-estimated their child's weight status. Many mothers of underweight children over-estimated (verbal 51.6%; visual 88.8%), and many mothers of overweight and obese children under-estimated (verbal 82.6%; visual 73.9%), their child's weight status. In contrast, significantly fewer mothers of normal-weight children were inaccurate (verbal 16.8%; visual 8.8%). Birth order (p<0.001), maternal (p = 0.004) and child's weight status (p<0.001) were associated with consistently inaccurate verbal and visual descriptions. CONCLUSIONS: Singaporean mothers, especially those of underweight and overweight children, may not be able to perceive their young child's weight status accurately. To facilitate prevention of childhood obesity, educating parents and caregivers about their child's weight status is needed. PMID- 26820667 TI - The Heterogeneity Hidden in Allergic Rhinitis and Its Impact on Co-Existing Asthma in Adults: A Population-Based Survey. AB - BACKGROUND: It has been suggested that there is some overlap between allergic rhinitis (AR), sinusitis and polyposis, but this has not been fully documented. The present study aimed to evaluate the prevalence of these co-existing diseases and their impact on bronchial asthma in the general population of Italy. METHODS: Within the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study, a postal screening questionnaire including questions about self-reported symptoms of asthma, AR, AR with sinusitis without nasal polyps (AR + SsNP) and AR with sinusitis with nasal polyps (AR + SwNP) was administered. Random samples of subjects aged between 20 and 44 years (n = 5,162) answered the postal questionnaire in 4 Italian centres (Pavia, Sassari, Turin, Verona). In AR subjects, the association among AR only, AR + SsNP, AR + SwNP and bronchial asthma was estimated by the relative risk ratio (RRR) using multinomial regression models. RESULTS: The prevalence of AR in the sample was 25.4% (95% CI 24.2-26.6). A self-reported diagnosis of AR + SsNP and AR + SwNP was reported by 5.7% (95% CI 5.0-6.3) and by 1.2% (95% CI 0.9-1.5) of the subjects, respectively. Current asthma was reported by 17.5% of the AR subjects. In the adjusted multivariate analysis, the risk of having current asthma (RRR = 2.31, 95% CI 1.29 4.15), of having at least 1 asthma attack per year (RRR = 2.30, 95% CI 1.19-4.46) and of having had an emergency department admission for respiratory diseases (RRR = 5.61, 95% CI 1.81-23.92) was higher for subjects with AR + SwNP than subjects with AR only. CONCLUSIONS: The diagnosis of AR in the epidemiological setting includes heterogeneous upper airway diseases that affect the clinical features of AR and its interactions with asthma. PMID- 26820668 TI - Intravoxel Incoherent Motion MR Imaging for Staging of Hepatic Fibrosis. AB - OBJECTIVES: To determine the potential of intravoxel incoherent motion (IVIM) MR imaging for staging of hepatic fibrosis (HF). METHODS: We searched PubMed and EMBASE from their inception to 31 July 2015 to select studies reporting IVIM MR imaging and HF staging. We defined F1-2 as non-advanced HF, F3-4 as advanced HF, F0 as normal liver, F1 as very early HF, and F2-4 as significant HF. Then we compared stage F0 with F1, F0-1 with F2-3, and F1-2 with F3-4 using IVIM-derived parameters (pseudo-diffusion coefficient D*, perfusion fraction f, and pure molecular diffusion parameter D). The effect estimate was expressed as a pooled weighted mean difference (WMD) with 95% confidence interval (CI), using the fixed effects model. RESULTS: Overall, we included six papers (406 patients) in this study. Significant differences in D* were observed between F0 and F1, F0-1 and F2 3, and F1-2 and F3-4 (WMD 2.46, 95% CI 0.83-4.09, P = 0.006; WMD 13.10, 95% CI 9.53-16.67, P < 0.001; WMD 14.34, 95% CI 10.26-18.42, P < 0.001, respectively). Significant differences in f were also found between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 1.62, 95% CI 0.06-3.18, P = 0.027; WMD 5.63, 95% CI 2.74 8.52, P < 0.001; WMD 3.30, 95% CI 2.10-4.50, P < 0.001, respectively). However, D showed no differences between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 0.05, 95% CI -0.01?0.11, P = 0.105; WMD 0.04, 95% CI -0.01?0.10, P = 0.230; WMD 0.02, 95% CI -0.02?0.06, P = 0.378, respectively). CONCLUSIONS: IVIM MR imaging provides an effective method of staging HF and can distinguish early HF from normal liver, significant HF from normal liver or very early HF, and advanced HF from non-advanced HF. PMID- 26820669 TI - Prenatal Associated Features in Fetuses Diagnosed with an Aberrant Right Subclavian Artery. AB - OBJECTIVE: The objective of this study was to determine the frequency and the nature of associated anomalies, especially malformations and chromosome abnormalities, in a population of fetuses with an aberrant right subclavian artery (ARSA). MATERIALS AND METHODS: This is a 7-year descriptive study. All patients whose fetus had an ARSA diagnosed by ultrasound performed during the 1st, 2nd, or 3rd trimester of pregnancy were included, regardless of their risk of chromosomal abnormalities. RESULTS: Between May 2007 and April 2014, an ARSA was diagnosed in 120 fetuses. The outcome was found in 108 cases (90%). ARSA was an isolated finding in 54/108 cases (50%). In 20% (22/108) of the fetuses, chromosomal abnormalities were detected. No chromosomal abnormalities were found in fetuses with an isolated ARSA. 82% (18/22) of chromosomal abnormalities were usual, such as trisomies 21 and 18, monosomy X, and 22q11.2 deletion. 21% (23/108) of the fetuses presenting an ARSA were associated with having a congenital heart disease. CONCLUSION: The presence of an isolated ARSA is a condition rarely associated with a chromosomal abnormality. The decision to perform an invasive karyotyping procedure under such circumstances or not may be made according to the principle of parental autonomy after extensive counselling and mostly a thorough assessment of the fetus. PMID- 26820670 TI - Surgery versus medical therapy for heavy menstrual bleeding. AB - BACKGROUND: Heavy menstrual bleeding significantly impairs the quality of life of many otherwise healthy women. Perception of heavy menstrual bleeding is subjective and management usually depends upon what symptoms are acceptable to the individual. Surgical options include conservative surgery (uterine resection or ablation) and hysterectomy. Medical treatment options include oral medication and a hormone-releasing intrauterine device (LNG-IUS). OBJECTIVES: To compare the effectiveness, safety and acceptability of surgery versus medical therapy for heavy menstrual bleeding. SEARCH METHODS: We searched the following databases from inception to January 2016: Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and clinical trials registers (clinical trials.gov and ICTRP). We also searched the reference lists of retrieved articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing conservative surgery or hysterectomy versus medical therapy (oral or intrauterine) for heavy menstrual bleeding. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, assessed their risk of bias and extracted the data. Our primary outcomes were menstrual bleeding, satisfaction rate and adverse events. Where appropriate we pooled the data to calculate pooled risk ratios (RRs) or mean differences, with 95% confidence intervals (CIs), using a fixed-effect model. We assessed heterogeneity with the I(2) statistic and evaluated the quality of the evidence using GRADE methods. MAIN RESULTS: We included 15 parallel-group RCTs (1289 women). Surgical interventions included hysterectomy and endometrial resection or ablation. Medical interventions included oral medication and the levonorgestrel-releasing intrauterine device (LNG-IUS). The overall quality of the evidence for different comparisons ranged from very low to moderate. The main limitations were lack of blinding, attrition and imprecision. Moreover, it was difficult to interpret long-term study findings as many women randomised to medical interventions subsequently underwent surgery. Surgery versus oral medicationSurgery (endometrial resection) was more effective in controlling bleeding at four months (RR 2.66, 95% CI 1.94 to 3.64, one RCT, 186 women, moderate quality evidence) and also at two years (RR 1.29, 95% CI 1.06 to 1.57, one RCT, 173 women, low quality evidence). There was no evidence of a difference between the groups at five years (RR 1.14, 95% CI 0.97 to 1.34, one RCT, 140 women, very low quality evidence).Satisfaction with treatment was higher in the surgical group at two years (RR 1.40, 95% CI 1.13 to 1.74, one RCT, 173 women, moderate quality evidence), but there was no evidence of a difference between the groups at five years (RR 1.13, 95% CI 0.94 to 1.37, one RCT, 114 women, very low quality evidence). There were fewer adverse events in the surgical group at four months (RR 0.26, 95 CI 0.15 to 0.46, one RCT, 186 women). These findings require cautious interpretation, as 59% of women randomised to the oral medication group had had surgery within two years and 77% within five years. Surgery versus LNG IUSWhen hysterectomy was compared with LNG-IUS, the hysterectomy group were more likely to have objective control of bleeding at one year (RR 1.11, 95% CI 1.05 to 1.19, one RCT, 223 women, moderate quality evidence). There was no evidence of a difference in quality of life between the groups at five or 10 years, but by 10 years 46% of women originally assigned to LNG-IUS had undergone hysterectomy. Adverse effects associated with hysterectomy included surgical complications such as bladder or bowel perforation and vesicovaginal fistula. Adverse effects associated with LNG-IUS were ongoing bleeding and hormonal symptoms.When conservative surgery was compared with LNG-IUS, at one year the surgical group were more likely to have subjective control of bleeding (RR 1.19, 95% CI 1.07 to 1.32, five RCTs, 281 women, low quality evidence, I(2) = 15%). Satisfaction rates were higher in the surgical group at one year (RR 1.16, 95% CI 1.04, to 1.28, six RCTs, 442 women, I(2) = 27%), but this finding was sensitive to the choice of statistical model and use of a random-effects model showed no conclusive evidence of a difference between the groups. There was no evidence of a difference between the groups in satisfaction rates at two years (RR 0.93, 95% CI 0.81 to 1.08, two RCTs, 117 women, I(2) = 1%).At one year there were fewer adverse events (such as bleeding and spotting) in the surgical group (RR 0.36, 95% CI 0.15 to 0.82, three RCTs, moderate quality evidence). It was unclear what proportion of women assigned to LNG-IUS underwent surgery over long-term follow-up, as there were few data beyond one year. AUTHORS' CONCLUSIONS: Surgery, especially hysterectomy, reduces menstrual bleeding more than medical treatment at one year. There is no conclusive evidence of a difference in satisfaction rates between surgery and LNG IUS, though adverse effects such as bleeding and spotting are more likely to occur with LNG-IUS. Oral medication suits a minority of women in the long term, and the LNG-IUS device provides a better alternative to surgery in most cases. Although hysterectomy is a definitive treatment for heavy menstrual bleeding, it can cause serious complications for a minority of women. Most women may be well advised to try a less radical treatment as first-line therapy. Both LNG-IUS and conservative surgery appear to be safe, acceptable and effective. PMID- 26820671 TI - Molecular and biochemical evidence on the protective effects of embelin and carnosic acid in isoproterenol-induced acute myocardial injury in rats. AB - AIMS: Acute myocardial infarction is a serious acute cardiac disorder and heart disease is still a major public health problem in adults. We investigated the effects of embelin (EMB) and carnosic acid (CA) in animals with isoproterenol (ISO)-induced myocardial injury. MAIN METHODS: Adult male Wistar-Albino rats were divided into four groups: control, ISO, ISO with EMB, and ISO with CA. Before myocardial injury was induced, drugs were administered by oral gavage. Myocardial injury was induced by subcutaneous injection of ISO hydrochloride for 2 consecutive days. Serum cardiac troponin I (cTnI), ischemia modified albumin (IMA), heart fatty acid binding protein (HFABP) levels and paraoxonase-1 (PON-1) activity, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), tumor necrosis factor-alpha (TNF-alpha) levels, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH-Px) activity were measured. Tissue mRNA expression levels of nuclear factor-kappa B (NF-kappaB), P38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor erythroid 2 related factor 2 (Nrf2) were analyzed. In addition, cardiac tissues were evaluated histopathologically and immunohistochemically. KEY FINDINGS: All tested compounds reduced myocardial damage, apoptosis, cTnI, IMA, HFABP, TOS, and TNF alpha levels, NF-kappaB, p38 MAPK, and phosphorylated c-Jun N-terminal protein kinase (pJNK 1/2) expressions. All tested compounds increased SOD activity, GSH Px activity, TAS levels, TT levels, phosphorylated extracellular signal-regulated kinase (pERK 1/2), and Nrf2 expressions. SIGNIFICANCE: Our results suggest that EMB and CA pretreatment could reduce myocardial injury via antiinflammatory, antioxidant, and antiapoptotic effects. PMID- 26820672 TI - Improvement of depressive behavior by Sweetme Sweet PumpkinTM and its active compound, beta-carotene. AB - AIMS: Sweetme Sweet PumpkinTM (SSP, baked Cucurbita moschata Duch.) has been used to treat patients with depression in Korea. However, the role of SSP in improving depression has not been elucidated yet. Thus, we assessed the antidepressant-like effect of SSP and its active compound, beta-carotene, with the forced swimming test (FST). MAIN METHODS: SSP and beta-carotene were orally administered once a day for 28days. The levels of brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase (pERK), and estrogen receptor-beta (ER-beta) were analyzed by Western blotting and quantitative real time-polymerase chain reaction. KEY FINDINGS: After 28days, treatment with SSP and beta-carotene significantly decreased the immobility time during the FST. SSP significantly increased the levels of serotonin and norepinephrine in the brain. The levels of BDNF, pERK, and ER-beta were significantly increased in the SSP- and beta-carotene-administered groups compared with the control group. In addition, the groups treated with SSP and beta-carotene showed significantly reduced levels of tumor necrosis factor-alpha and interleukin-6 compared with the control group. SIGNIFICANCE: In conclusion, these findings suggest the potential of SSP and beta-carotene as a novel therapeutic agent for the treatment of depression. PMID- 26820673 TI - Elevated Serum Brain-Derived Neurotrophic Factor (BDNF) but not BDNF Gene Val66Met Polymorphism Is Associated with Autism Spectrum Disorders. AB - The aim of our study was to illuminate the potential role of brain-derived neurotrophic factor (BDNF) in autism spectrum disorder (ASD). We measured the circulating levels of BDNF in serum and BDNF gene (Val66Met) polymorphisms, in which two indicators were then compared between ASD and normal controls. A total of 82 drug-naive ASD children and 82 age- and gender-matched normal controls were enrolled in the study. Their serum BDNF levels were detected by the ELISA. BDNF Val66Met polymorphism genotyping was conducted as according to the laboratory's standard protocol in laboratory. The ASD severity assessment was mainly determined by the score of the Childhood Autism Rating Scale (CARS). ELISA assay showed that the mean serum BDNF level of children with ASD was significantly (P < 0.0001) higher than that of the control cases (17.75 +/- 5.43 vs. 11.49 +/- 2.85 ng/ml; t = 9.236). Besides, the serum BDNF levels and CARS scores (P < 0.0001) were positively related. And, the BDNF genotyping results showed that there was no difference between the ASD cases and the control. Among the children with ASD, the mean serum BDNF level of Met/Met group was lower than other groups. According to the ROC curve generated from our clinical data, the optimal cutoff value of serum BDNF levels, an indicator for diagnosis of ASD, was projected to be 12.50 ng/ml. Thus, it yielded a corresponding sensitivity of 81.7 % and the specificity of 66.9 %. Accordingly, area value under the curve was 0.836 (95 % CI, 0.774 0.897); the positive predictive value (PPV) and the negative predictive value (NPV) were 70.1 and 79.1 %, respectively. These results suggested that rather than Val66Met polymorphism, BDNF was more possible to impact the pathogenesis of ASD. PMID- 26820674 TI - Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism and Alzheimer Disease Risk: a Meta-Analysis. AB - Methylenetetrahydrofolate reductase (MTHFR) is key enzyme of folate/homocysteine pathway. Case control association studies on MTHFR C677T polymorphism and Alzheimer's disease (AD) have been repeatedly performed over the last two decades, but the results are inconclusive. The aim of the present study was to assess the risk of MTHFR C677T polymorphism for AD. Forty-one studies were identified by a search of PubMed, Google Scholar, Elsevier, and Springer Link databases, up to January 2015. Odds ratios (ORs) with corresponding 95 % confidence interval (CI) were calculated using fixed effect model or random effect model. The subgroup analyses based on ethnicity were performed. MTHFR C677T polymorphism had a significant association with susceptibility to AD in all genetic models (for T vs C OR = 1.29, 95 % CI = 1.07-1.56, p = 0.003; for TT + CT vs CC OR = 1.29, 95 % CI = 1.19-1.40, p = 0.0004; for TT vs CC OR = 1.31, 95 % CI = 1.16-1.48, p = 0.001; for CT vs CC OR = 1.24, 95 % CI = 1.13-1.35, p < 0.004; and for TT vs CT + CC OR = 1.13, 95 % CI = 1.00-1.28, p = 0.02). Results of present meta-analysis supported that the MTHFR C677T polymorphism was associated with an increased risk of AD. PMID- 26820675 TI - PGRN Is Associated with Late-Onset Alzheimer's Disease: a Case-Control Replication Study and Meta-analysis. AB - Progranulin (PGRN) plays an important role in Alzheimer's disease (AD) through participating in altering neurite outgrowth and neuronal survival. Previous studies identified that rs5848 in the 3'-untranslated region (3'-UTR) of the PGRN gene (GRN) is strongly associated with AD in Caucasians. In order to assess the involvement of the GRN polymorphism in the risk of late-onset AD (LOAD), we analyzed the genotype and allele distributions of rs5848 in 2350 Han Chinese subjects (AD, 992; control, 1358). The minor T allele of rs5848 was significantly associated with an increased risk of LOAD (P = 0.005, odds ratio (OR) = 1.197, 95 % confidence interval (CI) = 1.057-1.355). Moreover, the association was further validated in the multivariate logistic regression analysis (dominant model: OR = 1.195, P = 0.038, recessive model: OR = 1.386, P = 0.025; additive model: OR = 1.187, P = 0.009). Interestingly, we observed that the interaction between apolipoprotein E (APOE) and rs5848 significantly altered the risk for AD. The rs5848 polymorphism was only significantly associated with LOAD in APOE epsilon4 allele carriers. Then we included five studies (including the present study) and conducted a meta-analysis which consisted of 3236 cases (male, 1152; female, 2084) and 3405 (male, 1436; female, 1969) controls. The result of the meta analysis supported T allele of rs5848 within GRN as a risk factor for AD. In conclusion, our results demonstrated that rs5848 polymorphism within GRN was associated with LOAD. PMID- 26820676 TI - Nr3C1-Bhlhb2 Axis Dysregulation Is Involved in the Development of Attention Deficit Hyperactivity. AB - Attention deficit hyperactivity disorder (ADHD) is a child developmental and behavioral disorder which seriously hinders their education and development. To investigate the key regulators in the prefrontal cortex (PFC), the major affected areas of ADHD, microRNA (miR)-138,138*, 34c*, 296, and 494, were noted for their significant downregulation in ADHD model rats spontaneously hypertensive rats (SHRs) compared to Wistar Kyoto (WKY) rat control. Based on promoter sequence analysis and activity assay, glucocorticoid receptor (Nr3c1) was identified for the inhibition of the promoter activity of miR-138-1, 34c*, 296, and 494 genes and their transcription. In the PFC of ADHD model rats SHR, Nr3c1 expression was abnormally elevated and reversely correlated with the levels of miR-138-1, 34c, 296, and 494 expression. Luciferase report assays indicated that all miR-138, 138*, 34c*, 296, and 494 targeted the 3' untranslated region of transcription factor Bhlhb2 (Bhlhe40) messenger RNA (mRNA) in common and ectopic expression of miR-138,138*, 34c*, 296, and 494 further suppressed the expression of Bhlhb2 gene. Consistently, Bhlhb2 expression was significantly higher in PFC of ADHD model SHR than control. Overexpressed Bhlhb2 in vitro significantly suppressed PC12 cell differentiation, and silence of Bhlhb2 enhanced the growth of neurite axon and dendrite. To observe the roles of Bhlhb2 further in vivo, Bhlhb2 was silenced in the PFC of nine SHR rats. Interestingly, knockdown of Bhlhb2 significantly improved the hyperactivity behaviors in SHRs compared to control. These findings show that Nr3c1-Bhlhb2 axis dysregulation was involved in the development of attention deficit and hyperactivity. PMID- 26820677 TI - Artesunate Protected Blood-Brain Barrier via Sphingosine 1 Phosphate Receptor 1/Phosphatidylinositol 3 Kinase Pathway After Subarachnoid Hemorrhage in Rats. AB - Blood-brain barrier preservation plays an important role in attenuating vasogenic brain edema after subarachnoid hemorrhage (SAH). This study was designed to investigate the protective effect and mechanism of artesunate, a traditional anti malaria drug, on blood-brain barrier after SAH. Three hundred and seventy-seven (377) male Sprague-Dawley rats were subjected to endovascular perforation model for SAH. The rats received artesunate alone or in combination with Sphingosine-1 phosphate receptor-1 (S1P1) small interfering RNA (siRNA), antagonist VPC23019, or phosphatidylinositol 3-kinase inhibitor wortmannin after SAH. Modified Garcia score, SAH grades, brain water content, Evans blue leakage, transmission electron microscope, immunohistochemistry staining, Western blot, and cultured endothelial cells were used to investigate the optimum concentration and the therapeutic mechanism of artesunate. We found that artesunate (200 mg/kg) could do better in raising modified Garcia score, reducing brain water content and Evans blue leakage than other groups after SAH. Moreover, artesunate elevated S1P1 expression, enhanced phosphatidylinositol 3-kinase activation, lowered GSK-3beta activation, stabilized beta-catenin, and improved the expression of Claudin-3 and Claudin-5 after SAH in rats. These effects were eliminated by S1P1 siRNA, VPC23019, and wortmannin. This study revealed that artesunate could preserve blood-brain barrier integrity and improve neurological outcome after SAH, possibly through activating S1P1, enhancing phosphatidylinositol 3-kinase activation, stabilizing beta-catenin via GSK-3beta inhibition, and then effectively raising the expression of Claudin-3 and Claudin-5. Therefore, artesunate may be favorable for the blood-brain barrier (BBB) protection after SAH and become a potential candidate for the treatment of SAH patients. PMID- 26820678 TI - Lentivirus-Mediated RNA Interference Targeting RhoA Slacks the Migration, Proliferation, and Myelin Formation of Schwann Cells. AB - RhoA, a member of Rho GTPases family, is known to play an important role in remodeling actin cytoskeleton. During the development of the peripheral nervous system (PNS), Schwann cells undergo proliferation, migration, and radial sorting and finally wrap the related axons compactly to form myelin sheath. All these processes involve actin cytoskeletal remodeling. However, the role of RhoA on Schwann cell during development is still unclear. To address this question, we first used a lentiviral vector-mediated short hairpin (sh) RNA targeting RhoA to knock down the expression of RhoA in the cultured Schwann cells in vitro. Effects of RhoA on Schwann cell proliferation and migration were examined by BrdU assay and transwell assay, respectively. Results of the present study indicated that downregulated RhoA expression in cultured Schwann cells significantly slacked the cells' capabilities of migration and proliferation. Then, we investigated the role of RhoA in the developing rat sciatic nerves. Immunohistology and Western blotting showed that RhoA was mainly expressed in Schwann cells in the sciatic nerves and was peaked at 2 weeks postnatal then kept in low level up to 8 weeks. In the subjected rats whose sciatic nerves were microinjected with lentiviral vectors at postnatal 3 days, we found that the lentiviruses mainly transfected Schwann cells, and the RhoA expression in the transfected Schwann cells was significantly knocked down. Four weeks after lentivirus microinjection, immunohistology and transmission electron microscopy illustrated that RhoA knockdown resulted in hypomyelination and significant decrease of the thickness of myelin in the transfected area. Overall data of current study suggested that RhoA plays a critical role in Schwann cell biology and is essential for myelination in developing peripheral nerve. PMID- 26820679 TI - Arachidonyl-2-Chloroethylamide Alleviates Cerebral Ischemia Injury Through Glycogen Synthase Kinase-3beta-Mediated Mitochondrial Biogenesis and Functional Improvement. AB - Arachidonyl-2-chloroethylamide (ACEA), a highly selective agonist of cannabinoid receptor 1 (CB1R), has been reported to protect neurons in ischemic injury. We sought to investigate whether mitochondrial biogenesis was involved in the therapeutic effect of ACEA in cerebral ischemia. Focal cerebral ischemic injury was induced in adult male Sprague Dawley rats. Intraperitoneal injection of 1 mg/kg ACEA improved neurological behavior, reduced infarct volume, and inhibited apoptosis. The volume and numbers of mitochondria were significantly increased after ACEA administration. Expression of mitochondrial transcription factor A (Tfam), nuclear transcription factor-1 (Nrf-1), and cytochrome C oxidase subunit IV (COX IV) were also significantly up-regulated in animals administered ACEA. One thousand nanomoles of ACEA inhibited mitochondrial dysfunction in primary rat cortical neurons exposed to oxygen-glucose deprivation (OGD). Furthermore, ACEA administration increased phosphorylation of glycogen synthase kinase-3beta (GSK 3beta) after reperfusion. Phosphorylation of GSK-3beta induced mitochondrial biogenesis and preserved mitochondrial function whereas inhibition of phosphatidylinositol 3-kinase (PI3K) dampened phosphorylation of GSK-3beta and reversed induction of mitochondrial biogenesis and function following ACEA administration. In conclusion, ACEA could induce mitochondrial biogenesis and improve mitochondrial function at the beginning of cerebral ischemia, thus alleviating cerebral ischemia injury. Phosphorylation of GSK-3beta might be involved in the regulation of mitochondrial biogenesis induced by ACEA. PMID- 26820680 TI - Exogenous Neural Stem Cells Transplantation as a Potential Therapy for Photothrombotic Ischemia Stroke in Kunming Mice Model. AB - Stroke is considered as the second leading cause of death worldwide. The survivors of stroke experience different levels of impairment in brain function resulting in debilitating disabilities. Current therapies for stroke are primarily palliative and may be effective in only a small population of stroke patients. In this study, we explore the transplantation of exogenous neural stem cells (NSCs) as the potential therapy for the photothrombotic ischemia stroke in a Kunming mice model. After stroke, mice receiving NSC transplantation demonstrated a better recovery of brain function during the neurobehavioral tests. Histology analysis of the brain samples from NSC transplanted mice demonstrated a reduction of brain damage caused by stroke. Moreover, immunofluorescence assay for biomarkers in brain sections confirmed that transplanted NSCs indeed differentiated to neurons and astrocytes, consistent with the improved brain function after stroke. Taken together, our data suggested that exogenous NSC transplantation could be a promising therapy for stroke. PMID- 26820682 TI - A systematic review on [(18)F]FLT-PET uptake as a measure of treatment response in cancer patients. AB - Imaging biomarkers have a potential to depict the hallmarks of cancers that characterise cancer cells as compared to normal cells. One pertinent example is 3'-deoxy-3'-(18)F-fluorothymidine positron emission tomography ([(18)F]FLT-PET), which allows non-invasive in vivo assessment of tumour proliferation. Most importantly, [(18)F]FLT does not seem to be accumulating in inflammatory processes, as seen in [(18)F]-fludeoxyglucose, the most commonly used PET tracer for assessment of cell metabolism. [(18)F]FLT could therefore provide additional information about the tumour biology before, during and after treatment. This systematic review focuses on the use of [(18)F]FLT-PET tumour uptake values as a measure of tumour response to therapeutic interventions. The clinical studies which evaluated the role of [(18)F]FLT-PET as a measure of tumour response to treatment are summarised and the evidence linking [(18)F]FLT-PET tumour uptake values with clinical outcome is evaluated. PMID- 26820681 TI - Combining Normobaric Oxygen with Ethanol or Hypothermia Prevents Brain Damage from Thromboembolic Stroke via PKC-Akt-NOX Modulation. AB - In a thromboembolic stroke model after reperfusion by recombinant tissue plasminogen activator (rt-PA), we aimed to determine whether therapeutic hypothermia (TH) and ethanol (EtOH) in combination with low concentration (60 %) of normobaric oxygen (NBO) enhanced neuroprotection, as compared to using each of these agents alone. We further aimed to elucidate a potential role of the NADPH oxidase (NOX), phosphorylated protein kinase B (Akt), and protein kinase C-delta (PKC-delta) pathway in oxidative stress and neuroprotection. In Sprague-Dawley rats, a focal middle cerebral artery (MCA) occlusion was induced by an autologous embolus in the following experimental groups: rt-PA treatment alone, rt-PA + NBO treatment, rt-PA + TH at 33 degrees C, rt-PA + EtOH, rt-PA + NBO + EtOH, rt-PA + NBO + TH, rt-PA + NOX inhibitor, rt-PA + EtOH + NOX inhibitor, or rt-PA + EtOH + Akt inhibitor. Control groups included sham-operated without stroke or stroke without treatment. Infarct volume and neurological deficit were assessed at 24 h after rt-PA-induced reperfusion with or without treatments. ROS levels, NOX activity, and the protein expression of NOX subunits p22phox, p47phox, p67phox, gp91phox, as well as PKC-delta and phosphorylated Akt were measured at 3 and 24 h after rt-PA-induced reperfusion. Following rt-PA in thromboembolic stroke rats, NBO combined with TH or EtOH more effectively decreased infarct volume and neurological deficit, as well as reactive oxygen species (ROS) production than with any of the used monotherapies. NOX activity and subunit expressions were downregulated and temporally associated with reduced PKC-delta and increased p Akt expression. The present study demonstrated that combining NBO with either TH or EtOH conferred similar neuroprotection via modulation of NOX activation. The results suggest a role of Akt in NOX activation and implicate an upstream PKC delta pathway in the Akt regulation of NOX. It is possible to substitute EtOH for TH, thus circumventing the difficulties in clinical application of TH through the comparatively easier usage of EtOH as a potential stroke management. PMID- 26820683 TI - Dosing to rash?--The role of erlotinib metabolic ratio from patient serum in the search of predictive biomarkers for EGFR inhibitor-mediated skin rash. AB - AIM: The aim of this study was to investigate if biomarkers of individual drug metabolism, respectively, the erlotinib/O-desmethyl-erlotinib metabolic ratio, may be a predictive factor for the severity of erlotinib-mediated skin rash in epidermal growth factor receptor (EGFR) inhibitor-treated patients suffering from epithelial cancers. This is especially important since it is known that the severity of skin rash has a prognostic value on outcome and survival in cancer patients experiencing skin rash under treatment with EGFR inhibitors. METHODS: From 2008 to 2014, 96 patients, n = 63 suffering from histologically confirmed non-small-cell lung cancer and n = 33 from pancreatic adenocarcinoma were observed for the occurrence and severity of skin rash after the onset of treatment with erlotinib. The primary end-points (occurrence and severity of skin rash, progression-free survival [PFS] and overall survival [OS]) were analysed with regard to erlotinib and its metabolite O-desmethyl-erlotinib trough serum concentrations measured at 4 weeks after onset of therapy by the use of correlation, multiple regression and survival analysis. RESULTS: Occurrence of skin rash was associated with PFS (p = 0.0042) and OS (p = 0.017) in the overall cohort of erlotinib-treated cancer patients. Drug-metabolising activity assessed by the erlotinib/O-desmethyl-erlotinib metabolic ratio was correlated with severity of skin rash (p = 0.023) and as well highly associated with both PFS (p = 2.1 * 10(-4)) and OS (p = 5.8 * 10(-5)). CONCLUSION: The erlotinib/O-desmethyl erlotinib metabolic ratio reflecting the individual metabolic activity of erlotinib correlated with the severity of skin rash and outcome in patients treated with EGFR tyrosine kinase inhibitors. The metabolic ratio determined in serum may be used for therapeutic monitoring in erlotinib treatment and decisions on individual dosing to rash in rash-negative patients. PMID- 26820684 TI - Diffuse large B-cell lymphoma with MYC gene rearrangements: Current perspective on treatment of diffuse large B-cell lymphoma with MYC gene rearrangements; case series and review of the literature. AB - In the past decade, patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. Standard treatment is now changing as a result of deeper understanding of underlying biologic differences of such lymphomas. One of the most powerful predictors of an adverse outcome on R-CHOP therapy is the presence of a MYC gene rearrangement (MYC+ lymphoma). Determination of MYC gene rearrangement by FISH (fluorescent in situ hybridisation) has recently become a standard diagnostic procedure. In this paper, an overview of current literature on MYC function and MYC+ lymphoma patient outcome is presented. Furthermore, we present 26 patients from our tertiary referral centre who were diagnosed with MYC+ lymphoma between 2009 and 2014. In our patient series, we confirm the dismal prognosis of MYC+ lymphoma patients. Intensification of classical chemotherapy does not lead to better overall survival, justifying new treatment modalities. First line therapy should be more specifically targeted against MYC and the genes and proteins that are deregulated by MYC. To this end, the first clinical trial in which MYC+ patients will be offered targeted treatment has recently been launched. PMID- 26820685 TI - Effects of T cell immunoglobulin and mucin domain-containing molecule-3 signaling molecule on human monocyte-derived dendritic cells with hepatitis B virus surface antigen stimulation in vitro. AB - The aim of the present study was to investigate the in vitro effects of hepatitis B virus surface antigen (HBsAg) on the immune function of human monocyte-derived dendritic cells (MD-DCs), and the moderating role of T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) signaling molecule. The monocytes, obtained from healthy adult peripheral blood, were incubated with recombinant human granulocyte-macrophage colony-stimulating factor and interleukin (IL)-4 to induce DCs. DC-associated cell markers were detected using flow cytometry. MD-DCs were treated with HBsAg (5 ug/ml) in vitro for 48 h and subsequently, cell markers, lymphocyte stimulatory capacity, signaling protein and downstream cytokines were assessed. In addition, a Tim-3 monoclonal antibody was used to inhibit the Tim-3 signaling pathway, and subsequently the immune responses of MD DCs to HBsAg stimulation were determined using the aforementioned method. The cell phenotype expressions of MD-DCs were all significantly increased with cluster of differentiation (CD)11c at 70.09+/-0.57%, human leukocyte antigen-DR at 79.83+/-2.12%, CD80 at 48.33+/-7.34% and CD86 at 44.21+/-5.35%. The treatment of MD-DCs with HBsAg resulted in a CD80 and CD86 enhanced expression, enhanced lymphocyte stimulatory capacity, upregulated expression of Tim-3 and nuclear factor-kappaB (NF-kappaB), as well as enhanced cytokine secretion of IL-6, IL-10 and interferon (IFN)-gamma. However, a reduced immune response of MD-DCs in response to HBsAg stimulation was observed when the Tim-3 signaling pathway was inhibited prior to stimulation. The expression of NF-kappaB was decreased and the cytokine secretion level of IL-6, IL-10 and IFN-gamma were downregulated. The treatment with HBsAg in vitro resulted in an enhanced immune response of MD-DCs, which may be positively regulated by the Tim-3 signaling molecule. PMID- 26820686 TI - Electrophysiology of cross-language interference and facilitation in picture naming. AB - Disagreement exists about how bilingual speakers select words, in particular, whether words in another language compete, or competition is restricted to a target language, or no competition occurs. Evidence that competition occurs but is restricted to a target language comes from response time (RT) effects obtained when speakers name pictures in one language while trying to ignore distractor words in another language. Compared to unrelated distractor words, RT is longer when the picture name and distractor are semantically related, but RT is shorter when the distractor is the translation of the name of the picture in the other language. These effects suggest that distractor words from another language do not compete themselves but activate their counterparts in the target language, thereby yielding the semantic interference and translation facilitation effects. Here, we report an event-related brain potential (ERP) study testing the prediction that priming underlies both of these effects. The RTs showed semantic interference and translation facilitation effects. Moreover, the picture-word stimuli yielded an N400 response, whose amplitude was smaller on semantic and translation trials than on unrelated trials, providing evidence that interference and facilitation priming underlie the RT effects. We present the results of computer simulations showing the utility of a within-language competition account of our findings. PMID- 26820687 TI - Short- and long-term effects of smoking on pain and health-related quality of life after non-instrumented lumbar spine surgery. AB - OBJECTIVES: A myriad of negative bodily health effects related to tobacco smoking is known while its detrimental effects on the spine in particular are less defined. The goal of the current study is to compare long-term outcome between smokers and non-smokers after non-instrumented lumbar spine surgery. PATIENTS AND METHODS: Prospective observational study on n=172 consecutive patients undergoing non-instrumented spine surgery for lumbar disc herniation (LDH) or lumbar spinal stenosis (LSS) with a follow-up (FU) of 4.5 years. Patients were dichotomized according to their smoking status at the time of surgery. Back pain and health related quality of life (HRQoL) were assessed using the visual analogue scale (VAS) and the Short-Form (SF)-12. Any subsequent lumbar spine surgeries since the index surgery were registered. Logistic regression analysis was used to estimate the effect size of the relationship between smoking and the responder status to surgery in terms of pain and HRQoL-metrics. RESULTS: Complete FU data was available for n=29 (55%) smokers and n=75 (63%) non-smokers. At discharge, 1 month, 1 year and 4.5 years, smokers were as likely as non-smokers to achieve a favourable response to surgery in terms of VAS back pain and the SF-12 mental and physical component scale metric. A subgroup analysis on active smokers throughout the entire study interval did not find an inferior responder rate than in never smokers. A trend for additional lumbar spine surgery performed in 17.2% of the smoking and 8.2% of the non-smoking patients during FU was observed (OR 2.39, 95% CI 0.67-8.57, p=0.179). CONCLUSION: Up to 4.5 years following non-instrumented lumbar spine surgery, there was no difference in the pain or HRQoL-responder status of smokers and non-smokers. Smokers may be more likely to undergo re-do surgery in the long term, but more data is needed to confirm this statistical trend. PMID- 26820688 TI - Working from Both Sides: Composite Metallic Semitransparent Top Electrode for High Performance Perovskite Solar Cells. AB - We report herein perovskite solar cells using solution-processed silver nanowires (AgNWs) as transparent top electrode with markedly enhanced device performance, as well as stability by evaporating an ultrathin transparent Au (UTA) layer beneath the spin-coated AgNWs forming a composite transparent metallic electrode. The interlayer serves as a physical separation sandwiched in between the perovskite/hole transporting material (HTM) active layer and the halide-reactive AgNWs top-electrode to prevent undesired electrode degradation and simultaneously functions to significantly promote ohmic contact. The as-fabricated semitransparent PSCs feature a Voc of 0.96 V, a Jsc of 20.47 mA cm(-2), with an overall PCE of over 11% when measured with front illumination and a Voc of 0.92 V, a Jsc of 14.29 mA cm(-2), and an overall PCE of 7.53% with back illumination, corresponding to approximately 70% of the value under normal illumination conditions. The devices also demonstrate exceptional fabrication repeatability and air stability. PMID- 26820689 TI - Pathways by which mothers' physiological arousal and regulation while caregiving predict sensitivity to infant distress. AB - Pathways by which maternal physiological arousal (skin conductance level [SCL]) and regulation (respiratory sinus arrhythmia [RSA] withdrawal) while parenting are linked with concurrent and subsequent maternal sensitivity were examined. Mothers' (N = 259) SCL and RSA were measured during a resting baseline and while interacting with their 6-month-old infants during tasks designed to elicit infant distress. Then, mothers were interviewed about their emotional and cognitive responses to infant cues (i.e., cry processing) while caregiving using a video recall procedure. Maternal sensitivity was observed during the distressing tasks at 6 months and again when children were 1-year-old. Mothers who were well regulated (higher RSA suppression from baseline to parenting tasks) engaged in less negative and self-focused cry processing while interacting with their infants, which in turn predicted higher maternal sensitivity at both time points. In addition, SCL arousal and RSA regulation interacted such that maternal arousal was associated with more empathic/infant focused cry processing among mothers who were simultaneously well-regulated, which in turn predicted maternal sensitivity, albeit only at 6 months. These effects were independent of a number of covariates demonstrating the unique role of mothers' physiological regulation while caregiving on sensitivity. Implications for intervention are discussed. (PsycINFO Database Record PMID- 26820690 TI - Emodin inhibits epithelial to mesenchymal transition in epithelial ovarian cancer cells by regulation of GSK-3beta/beta-catenin/ZEB1 signaling pathway. AB - Emodin (EMO) has been shown to possess pleiotropic anticancer capabilities in many types of cancer, including epithelial ovarian cancer (EOC). Inhibitory efficacy of EMO on EOC invasion and migration was previously observed, however, the underlying mechanisms have not been completely elucidated. The present study is aimed to explore the mechanisms. Transwell assay demonstrated that EMO significantly inhibited A2780 and SK-OV-3 cell invasion. Western blot analysis was performed to detect the expression levels of epithelial to mesenchymal transition (EMT)-related markers. We found that EMO treatment dose-dependently upregulated E-cadherin, keratin and downregulated N-cadherin, vimentin, matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) to repress EMT. Mechanistically, EMO could inhibit glycogen synthase kinase 3beta (GSK 3beta) phosphorylation, decrease total beta-catenin protein levels and subsequently downregulate transcription factor zinc finger E-box binding homeobox 1 (ZEB1) expression. These effects of EMO were weakened when the cells were pretreated with SB216763, an inhibitor of GSK-3beta kinase. Besides, we utilized small interfering RNA (siRNA) to downregulate ZEB1 expression. We found that treatment of ZEB1-knockdown cells with EMO, ZEB1 levels were lowest and cell invasion was weakest but ZEB1 knockdown had no effect on the expression of phospho-Ser9-GSK-3beta (p-GSK-3betaSer9), beta-catenin. In conclusion, our results suggested that EMO inhibited EOC cell invasion by regulation of GSK 3beta/beta-catenin/ZEB1 signaling pathway to suppress EMT in vitro. PMID- 26820691 TI - A label-free differential proteomics analysis reveals the effect of melatonin on promoting fruit ripening and anthocyanin accumulation upon postharvest in tomato. AB - To better understand the function of melatonin in tomato fruit ripening and quality improvement, a label-free quantitation method was used to investigate the proteins that differ between the control (CK) and 50 MUm melatonin treatment (M50) fruits. Proteomics data identified 241 proteins that were significantly influenced by melatonin. These proteins were involved in several ripening-related pathways, including cell wall metabolism, oxidative phosphorylation, carbohydrate, and fatty acid metabolism. Moreover, the application of exogenous melatonin increased eight proteins that are related to anthocyanin accumulation during fruit ripening. Additionally, the affected protein levels correlated with the corresponding gene transcript levels. Further, the total anthocyanin content from M50 increased by 52%, 48%, and 50% at 5, 8, and 13 DAT (day after melatonin treatment), respectively. The melatonin-mediated promotion of fruit ripening and quality might be due to the altered proteins involved in processes associated with ripening. In this work, we indicated that a senescence-related protein was downregulated in the M50 fruit, while a cell apoptosis inhibitor (API5) protein was upregulated. In addition, peroxidases (POD9, POD12, peroxidase p7-like) and catalase (CAT3) significantly increased in the M50 fruits. Based on the previous studies and our data, we inferred that melatonin might be positively related to fruit ripening but negatively related to fruit senescence. This research provides insights into the physiological and molecular mechanisms underlying melatonin mediated fruit ripening as well as the anthocyanin formation process in tomato fruit at the protein concentration level, and we reveal possible candidates for regulation of anthocyanin formation during fruit ripening. PMID- 26820693 TI - Regorafenib as a potential adjuvant chemotherapy agent in disseminated small colon cancer: Drug selection outcome of a novel screening system using nanoimprinting 3-dimensional culture with HCT116-RFP cells. AB - Colon cancer is one of the leading causes of cancer death worldwide. Adjuvant chemotherapy following primary surgical treatment is suggested to be beneficial in eradicating invisible disseminated small tumors in colon cancer; however, an effective drug remains to be developed. Recently, we reported a novel drug screening system using a nanoimprinting 3-dimensional (3D) culture that creates multicellular spheroids, which simulate in vivo conditions and, thereby, predict effective drugs in vivo. This study aimed to perform drug selection using our recently developed 3D culture system in a human colon cancer HCT116 cell line stably expressing red fluorescent protein (HCT116-RFP), to determine the most effective agent in a selection of clinically used antitumor agents for colon cancer. In addition, we confirmed the efficacy of the selected drug regorafenib, in vivo using a mouse model of disseminated small tumors. HCT116-RFP cells were cultured using a nanoimprinting 3D culture and in vitro drug selection was performed with 8 clinically used drugs [bevacizumab, capecitabine, cetuximab, 5 fluorouracil (5-FU), irinotecan, oxaliplatin, panitumumab and regorafenib]. An in vivo study was performed in mice bearing HCT116-RFP intraperitoneally disseminated small tumors using 3'-[18F]-fluoro-3'-deoxythymidine-positron emission tomography and fluorescence microscopy imaging to evaluate the therapeutic effects. Regorafenib was determined to be the most effective drug in the 3D culture, and significantly inhibited tumor growth in vivo, compared to the untreated control and 5-FU-treated group. The drug 5-FU is commonly used in colon cancer treatment and was used as a reference. Our results demonstrate that regorafenib is a potentially efficacious adjuvant chemotherapeutic agent for the treatment of disseminated small colon cancer and, therefore, warrants further preclinical and clinical studies. PMID- 26820695 TI - Glaucoma neurorecovery - a sugar-coated road to retinal ganglion cell recovery. PMID- 26820697 TI - Claudin-1 expressions decrease in pterygium with respect to normal conjunctiva. AB - CONTEXT: Pterygium is the fibrovascular growth of the limbal conjunctiva over cornea. This proliferative nature might have a pathogenesis associated with tight junction proteins. OBJECTIVE: To investigate the tight junction protein claudin-1 expressions in pterygium with respect to normal conjunctiva. MATERIALS AND METHODS: This retrospective study included 28 patients who underwent pterygium surgery with autograft. Claudin-1 expressions were immunohistochemically evaluated in normal and lesional conjunctiva of the same eye. Immunohistochemical evaluation was done with regard of both the intensity and the extent of staining. The distribution of the immunohistochemical scores in pterygium and normal conjunctiva has been compared with using McNemar test. RESULTS: The mean age of the patients was 52.2 +/- 11.2 years and male/female ratio was 8/20. Among 28 samples of normal conjunctiva 25 (89.2%) demonstrated a strong immunohistochemical expression with claudin-1 whereas this rate was 10.8% for pterygium samples. Statistical analysis revealed a significant decrease in claudin-1 expressions in pterygium with respect to normal conjunctiva (p < 0.001). DISCUSSION AND CONCLUSIONS: The loss of claudin-1 appears to be involved in the pathogenesis of pterygium and the future studies will elucidate the exact role of tight junction proteins in the invasive and recurrent nature of pterygium. PMID- 26820698 TI - Application of the perfusion index in obstetric bleeding. AB - OBJECTIVE: We assessed the utility of the pulse oximeter perfusion index (PI) in maternal monitoring immediately after delivery. METHODS: We examined 30 pregnant women without any complications using the Rad7 device at delivery. The correlations between heart rate (HR), systolic blood pressure (BP), oxygen saturation SpO2, PI, Pleth variability index (PVI), shock index and blood loss were assessed. RESULTS: Blood loss at 20-min postpartum was not correlated with the difference in heart rate, systolic BP, SpO2, shock index or PVI taken immediately after delivery and at 20-min postpartum, but showed a strong negative correlation with the difference in the PI taken immediately after delivery and at 20-min postpartum (r = -0.70). CONCLUSION: PI changes were correlated with post delivery blood loss and can be used for maternal monitoring at delivery. PMID- 26820700 TI - Potential for Integrating Diffusion of Innovation Principles into Life Cycle Assessment of Emerging Technologies. AB - Life cycle assessment (LCA) measures cradle-to-grave environmental impacts of a product. To assess impacts of an emerging technology, LCA should be coupled with additional methods that estimate how that technology might be deployed. The extent and manner that an emerging technology diffuses throughout a region shapes the magnitude and type of environmental impacts. Diffusion of innovation is an established field of research that analyzes the adoption of new innovations, and its principles can be used to construct scenario models that enhance LCA of emerging technologies. Integrating diffusion modeling techniques with an LCA of emerging technology can provide estimates for the extent of market penetration, the displacement of existing systems, and the rate of adoption. Two general perspectives of application are macro-level diffusion models that use a function of time to represent adoption, and microlevel diffusion models that simulate adoption through interactions of individuals. Incorporating diffusion of innovation concepts complement existing methods within LCA to inform proactive environmental management of emerging technologies. PMID- 26820699 TI - A delayed injection-site reaction in a patient receiving extended-release naltrexone. AB - BACKGROUND: Pharmacotherapy, such as oral naltrexone, has proven effective in treating alcohol use disorder, although medication adherence has presented challenges. Although a formulation of extended-release naltrexone for intramuscular injection has been developed to counter daily adherence issues, injection-site reactions can occur within days of depot injection. CASE: The authors report a case of an individual with alcohol use disorder who had a previously undescribed delayed injection-site reaction that occurred 11 days after injection. Subsequent challenge with the medication resulted in recurrence of the reaction. DISCUSSION: Although extended-release naltrexone is generally well tolerated, injection-site reactions can complicate treatment and can appear more than 10 days after medication administration. PMID- 26820701 TI - The influence of the WWOX gene on the regulation of biological processes during endometrial carcinogenesis. AB - The purpose of the present study was to investigate the role of WW domain containing oxidoreductase (WWOX) downregulation in biological cancer-related processes in normal (non-malignant) and cancer endometrial cell lines. We created an in vitro model using the normal endometrial cell line, THESC, and 2 endometrial cancer cell lines with varying degrees of differentiation, the Ishikawa (well-differentiated) and the MFE296 (moderately differentiated) cells, in which the WWOX tumor suppressor gene was silenced using Gipz lentiviral shRNA. In this model, we examined the changes in invasiveness via biological assays, such as zymography, migration through a basement membrane, the adhesion of cells to extracellular matrix proteins, anchorage-independent growth and colony formation assay. We also evaluated the correlation between the mRNA expression of the WWOX gene and genes involved in the processes of carcinogenesis, namely catenin beta-1 (CTNNB1) and zinc finger E-box binding homeobox 1 (ZEB1) (gene transcription), cadherin 1 (CDH1) and ezrin (EZR) (cell adhesion), vimentin (VIM) (structural proteins), as well as phosphatase and tensin homolog (PTEN) (tumor suppression) and secreted protein, acidic, cysteine-rich (osteonectin) (SPARC) (SPARC) (cell growth regulation) by RT-qPCR. Downregulation of the WWOX gene in the moderately differentiated MFE296 cell line caused decreased migratory capacity, and a reduction of matrix metalloproteinase-2 (MMP-2) activity. However, these cells grew in semisolid medium and exhibited higher expression of CDH1 and EZR (cell adhesion) and secreted protein, acidic, cysteine-rich (osteonectin) (SPARC) (cell growth regulation). Moreover, in the well differentiated endometrial cancer (Ishikawa) cell line, WWOX gene silencing resulted in an increased ability of the cells to proliferate indefinitely. Additionally, WWOX regulated changes in adhesion potential in both the normal and cancer cell lines. Our results suggest that the WWOX tumor suppressor gene modulated the processes of cell motility, cell adhesion, gene expression and remodeling in endometrial cell lines. PMID- 26820702 TI - Who Leaves Suicide Notes? An Exploration of Victim Characteristics and Suicide Method of Completed Suicides in Queensland. AB - The objective of this study is to address the question: are those who leave suicide notes representative of the larger population of those who commit suicide? The method involves an analysis of a full population of suicides by residents of Queensland, Australia for the full year of 2004, with the information drawn from Coronial files. Our overall results suggest that, and in support of previous research, the population who leaves suicide notes are remarkably similar to those who do not. Differences are identified in four areas: first, and in contrast to prior research, females are less likely to leave a suicide note; second, and in support of previous research, Aboriginal Australians are less likely to leave suicide notes; third, and in support of some previous research, those who use gas as a method of suicide are more likely to leave notes, while those who use a vehicle or a train are less likely to leave notes; finally, our findings lend support to research which finds that those with a diagnosed mental illness are less likely to leave notes. The discussion addresses some of the reasons these disparities may have occurred, and continues the debate over the degree to which suicide notes give insight into the larger suicide population. PMID- 26820703 TI - Behavioral Characteristics Of Children : Replication Studies With Foster Children. AB - A replication study of rated behavioral characteristics of children is shown to yield stable factor structures for two groups of observers: foster mothers and social workers. Stability of cluster scores of ratings is established, as is agreement between the two classes of observers. Cluster scores are shown to differentiate between outpatient and foster children groups of subjects. It is also found that social workers consistently rate foster children in the direction of more pathology than do the foster mothers. PMID- 26820704 TI - The Multidimensional Scaling Of A Set Of Artistic Drawings : Perceived Structure And Scale Correlates. AB - Product-centered research on creativity approaches the criterion problem of what is to be the referent for creativity through the analysis of tangible products such as a r t objects, writing, or scientific achievements. The present research is concerned with the evaluation and study of artist drawings contributed by sophomore students a t the Rhode Island School of Design. Multi-dimensional scaling methods were applied to similarity judgments obtained from art experts on two separate sets of 26 drawings. Three similarity dimensions accounted for the interstimulus distances for each set of drawings. Although no statistical test was available, the dimensions from the two seta appeared to correspond. Scale values of 4 drawings common to the two sets were consistent, and the dimensions appeared to define very similar stimulus characteristics. It was concluded that multidimensional scaling procedures provided a means for differentiating among a set of complex, esthetic products. Scale values of drawings on the three dimensions also correlated differentially with cognitive and achievement measures available on the students, suggesting that product dimensions identified via similarity judgments were related to characteristics of individuals producing the products. Hypotheses were developed as to the psychological meaning of the three product dimensions. PMID- 26820705 TI - Dimensions Of Leadership In A Student Cooperative. AB - Homans (1960) analyzed leadership phenomena in terms of four major constructs, activity, interaction, aentiment, and norm. The present study developed an instrument to represent three of Homans' constructs and tested propositions based on his theory of small group leadership. Fifteen subjects, five each at three leadership levels, were rated by close associates and also rated themselves. With one exception (norms) the propositions derived from Homans' theory were supported by the results. PMID- 26820706 TI - Relations Between Conscious And Unconscious Manifestations Of Motivation In Children. AB - Interest strength in 36 attitudes was measured on 89 public school students by means of four indirect behavioral tests. Standard scores on Word Association and Information were combined to give the Integrated (conscious) scores, and those on Selective Memory and Autism were combined to give the Unintegrated (unconscious) scores. Eighteen hypothesized drive factors and four device factors were extracted. The centroid was partitioned, and the Unintegrated portion was rotated by Procrustes for pure drive factors. This portion was projected upon the Integrated realm by reassembling the centroid matrix, and rotating the whole to the Procrustes position obtained for the part. Overall results appeared to support the "structural" rather than the "topographic" approaches t o psychoanalytic theory. PMID- 26820707 TI - A Stochastic Model For Repeated Testing. AB - The paper suggests an extension of current probability models of mental testing to include practice effects resulting when the same subject responds t o the same ability test item on several occasions. The method involves the treatment of multiple presentations of the same item as a stochastic process, Le., a series of interrelated stochastic events. Some general results are presented and a particular model for practice effects utilizing the latent classes and linear operator learning models1 is discussed a t some length. Methods of parameter estimation and testing goodness of fit are presented and illustrated with a numerical example. PMID- 26820708 TI - Classification Space: A Multivariate Procedure For Automatic? Document Indexing And Retrieval. AB - A conceptual approach to linguistic data processing problems is sketched and empirical illustrations are presented of the major software components- indexing, storage, and retrieval-of a document processing system which offers, in principle, the advantages of complete automation, unlimited cross- indexing, effective sequential retrieval, sub-documentary indexing reflecting heterogeneity of subject matter within a document, and a procedure for automatically identifying retrieval requests which would be inadequately handled by the system. The indexing schema, designated as a "Classification Space" consists of a Euclidean model for mapping subject matter similarity within a given subject matter domain. A schema of this kind is empirically derived for certain fields of Engineering and Chemistry. A set of five related empirical studies provide convincing evidence that when appropriate experimental procedures are followed a very stable C-Space for a given content domain can be constructed on a surprisingly small data base. Other empirical studies demonstrate specific computational procedures for effective automatic indexing of documents in a C Space, using a relatively small system vocabulary. One study demonstrates that a C-Space maps subject matter relevance as well as subject matter similarity, and thereby pro- motes effective sequential retrieval ; this result is also shown under conditions of automatic indexing. Negative results are found in an attempt to use the structural linguistic distinction of subject and object as a means of improving techniques for automatic indexing. PMID- 26820709 TI - Access-Related Infections Involving the Buttonhole Technique. AB - PURPOSE: In this study, we discuss a mechanism of development of access-related Staphylococcus aureus infections in patients on buttonhole (BH) method and logically construct a measure to prevent such infections on the basis of the mechanism. SUMMARY: S. aureus can colonize a BH track. Once S. aureus colonizes a BH track, access-related infections may develop when the equilibrium is upset between the factors of host resistance and a level of bacterial growth in a BH track. Thus, the logically constructed measure to prevent access-related infections are as follows: (1) decolonization of S. aureus from a BH track by applying mupirocin ointment to a BH entry site when a patient has been proven to be a carrier of S. aureus in the track, (2) prevention of bacterial invasion of the BH track by a new method to remove a scab completely, and (3) control of bacterial growth in the BH track by disinfecting the site with diluted povidone iodine solution (0.1% povidone-iodine solution) before access vessel cannulation. PMID- 26820710 TI - Multimodal Interventions to Enhance Adherence to Secondary Preventive Medication after Stroke: A Systematic Review and Meta-Analyses. AB - INTRODUCTION: Nonadherence to secondary preventative medications after stroke is common and is associated with poor outcomes. Numerous strategies exist to promote adherence. We performed a systematic review and meta-analysis to describe the efficacy of strategies to improve adherence to stroke secondary prevention. METHODS: We created a sensitive search strategy and searched multiple electronic databases (MEDLINE, EMBASE, CINAHL, PsycINFO, CENTRAL, and Web of Knowledge) for studies of interventions that aimed to enhance adherence to secondary preventative medication after stroke. We assessed quality of included studies using the Cochrane tool for assessing risk of bias. We performed narrative review and performed meta-analysis where data allowed. RESULTS: From 12,237 titles, we included seventeen studies in our review. Eleven studies were considered to have high risk of bias, 3 with unclear risk, and 3 of low risk. Meta-analysis of available data suggested that these interventions improved adherence to individual medication classes (blood pressure-lowering drugs - OR, 2.21; 95% CI (1.63, 2.98), [P < 0.001], lipid-lowering drugs - OR, 2.11; 95% CI (1.00, 4.46), [P = 0.049], and antithrombotic drugs - OR, 2.32; 95% CI (1.18, 4.56, [P = 0.014]) but did not improve adherence to an overall secondary preventative medication regimen (OR, 1.96; 95% CI (0.50, 7.67), [P = 0.332]). CONCLUSION: Interventions can lead to improvement in adherence to secondary preventative medication after stroke. However, existing data is limited as several interventions, duration of follow-up, and various definitions were used. These findings need to be interpreted with caution. PMID- 26820711 TI - Neuronal nitric oxide synthase contributes to pentylenetetrazole-kindling-induced hippocampal neurogenesis. AB - Neuronal nitric oxide synthase (nNOS), the major nitric oxide synthase isoform in the mammalian brain, is implicated in the pathophysiology of several neurological conditions, including epilepsy. Neurogenesis in hippocampal dentate gyrus (DG) persists throughout life in the adult brain. Alterations in this process occur in many neurological diseases, including epilepsy. Few studies, however, have addressed the role of nNOS in hippocampal DG neurogenesis in epileptic brain. The present study, therefore, investigated the role of nNOS in pentylenetetrazole (PTZ)-kindling-induced neurogenesis in hippocampal DG. Our results showed that nNOS expression and enzymatic activity were significantly increased in the hippocampus of PTZ-kindled mice. Meanwhile, these PTZ-kindled mice were characterized by significant enhancement of new born cells proliferation and survival in hippocampal DG, and these survived cells are co-labeled with NeuN and GFAP. Selective inhibition of nNOS by 7-NI, however, suppressed PTZ-kindling induced hippocampal DG new born cells proliferation and survival, suggesting that nNOS contributes to PTZ-kindling-induced hippocampal neurogenesis. PMID- 26820712 TI - Aberrant expression of Golgi protein 73 is indicative of a poor outcome in hepatocellular carcinoma. AB - Golgi protein 73 (GP73), a resident Golgi type-II membrane protein, is often upregulated in hepatocytes. In the present study, shRNA-mediated suppression of GP73 expression in hepatocellular carcinoma (HCC) cell lines (MHCC97H, HCCLM3) resulted in a significant inhibition of cell motility and invasion and also led to the regression of epithelial-mesenchymal transition phenotypes. In contrast, overexpression of GP73 in the SMMC7721 cell line retrieved the expression of EMT markers, and promoted cell motility and invasion. High expression of GP73 was also found in HCC tissues with metastasis, as detected by western blot and immunohistochemistry analyses. Kaplan-Meier survival analysis showed that the survival of patients with high GP73 expression was significantly poorer than that of patients with low GP73 expression (p=0.027). Our findings demonstrated an important role of GP73 in HCC metastasis, and indicated that GP73 is a candidate target for HCC therapy. PMID- 26820713 TI - Intrathoracic Rosai Dorfman Disease with Focal Aggregates of IgG4-bearing Plasma Cells. Case Report and Literature Review. AB - Rosai Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy, is a rare histiocytic disorder that typically presents as painless cervical adenopathy. Occasionally, Rosai Dorfman disease may involve extranodal sites and it can be associated with constitutional symptoms. In this report, we present a patient with progressive dyspnea on exertion, obstruction on spirometry, and paratracheal soft tissue thickening extending to the proximal bronchi and hila. After extensive radiologic and interventional measures, including multiple biopsies, the diagnosis was established on pathology showing characteristic features of Rosai Dorfman disease in a paratracheal lymph node and features of extranodal Rosai Dorfman disease with extensive fibrosis in the paratracheal mass. In addition, the involved paratracheal lymph node demonstrated focally increased IgG4-positive plasma cells, a finding that was not present in the tracheal mass. A review of intrathoracic manifestations of Rosai Dorfman disease including the proposed causes and causative triggers is presented. The histological features and the current understanding of the management and prognosis are also discussed. This unusual presentation highlights the need to consider histiocytic disorders in the differential diagnosis of paratracheal disease. PMID- 26820715 TI - Ten Years of Optimizing Outcomes for Women With Type 1 and Type 2 Diabetes in Pregnancy-The Atlantic DIP Experience. AB - CONTEXT: Pregnancy for women with type 1 or type 2 diabetes is a time of increased risk for both mother and baby. The Atlantic Diabetes in Pregnancy program provides coordinated, evidence-based care for women with diabetes in Ireland. Founded in 2005, the program now shares outcomes over its first decade in caring for pregnant women with diabetes. OBJECTIVE: The objective was to assess improvements in clinical outcomes after the introduction of interventions. DESIGN, SETTING, PARTICIPANTS: We retrospectively examined 445 pregnancies in women with type 1 and type 2 diabetes and compared them over two timepoints, 2005 2009 and 2010-2014. INTEVENTIONS: Interventions introduced over that time include: provision of combined antenatal/diabetes clinics, prepregnancy care, electronic data management, local clinical care guidelines, professional and patient education materials, an app, and a web site. MAIN OUTCOMES: Pregnancy outcomes were measured. RESULTS: The introduction of the Atlantic Diabetes in Pregnancy program has been associated with a reduction in adverse neonatal outcomes. There has been a reduction in congenital malformations (5 to 1.8%; P = .04), stillbirths (2.3 vs 0.4%; P = .09), despite an upward trend in maternal age (mean age, 31.7 vs 33 years), obesity (29 vs 43%; body mass index >30 kg/m2), and excessive gestational weight gain (24 vs 38%; P = .002). These improvements in outcomes occur alongside an increase in attendance at prepregnancy care (23 to 49%; P < .001), use of folic acid (45 vs 71%; P < .001), and sustained improvement in glycemic control. CONCLUSIONS: Changing the process of clinical care delivery and utilizing evidence-based interventions in a pragmatic clinical setting improves pregnancy outcomes for women with pregestational diabetes. We now need to target optimization of maternal body mass index before pregnancy and put a greater focus on gestational weight gain through education and monitoring. PMID- 26820714 TI - Vitamin D3 Inhibits Wnt/beta-Catenin and mTOR Signaling Pathways in Human Uterine Fibroid Cells. AB - CONTEXT: Somatic mutations in the Med12 gene are known to activate Wnt/beta catenin signaling in human uterine fibroids (UFs). OBJECTIVE: The objective of the study was to examine the role of vitamin D3 in the modulation of Wnt/beta catenin and mammalian target of rapamycin (mTOR) signaling in human UF cells. DESIGN: Immortalized human UF cells (HuLM) and human primary UF (PUF) cells were treated with increasing concentrations of vitamin D3 and thereafter analyzed using Western blots and immunocytochemistry. MAIN OUTCOME MEASURES: Wnt/beta catenin and mTOR signaling proteins in cultured HuLM and PUF cells were measured. RESULTS: UF tumors with Med12 somatic mutations showed an up-regulation of Wnt4 and beta-catenin as compared with adjacent myometrium. Vitamin D3 administration reduced the levels of Wnt4 and beta-catenin in both HuLM and PUF cells. Vitamin D3 also reduced the expression/activation of mTOR signaling in both cell types. In contrast, vitamin D3 induced the expression of DNA damaged-induced transcription 4 (an inhibitor of mTOR) and tuberous sclerosis genes (TSC1/2) in a concentration-dependent manner in HuLM cells. Furthermore, we observed a concentration-dependent reduction of Wisp1 (Wnt induced signaling protein 1) and flap endonuclease 1 proteins in HuLM cells. Additionally, abrogation of vitamin D receptor expression (by silencing) in normal myometrial cells induces Wnt4/beta catenin as well as prompts a fibrotic process including an increase in cell proliferation and increased extracellular matrix production. Together these results suggest that vitamin D3 functions as an inhibitor of Wnt4/beta-catenin and mTOR signaling pathways, which may play major roles in fibroid pathogenesis. CONCLUSIONS: Vitamin D3 may have utility as a novel long-term therapeutic and/or preventive option for uterine fibroids. PMID- 26820716 TI - Atomic and electronic structure transformations in SnS2 at high pressures: a joint single crystal X-ray diffraction and DFT study. AB - The layered semiconductor SnS2 spurs much interest for both intercalation and optoelectronic applications. Despite the wealth of research in the field of metal dichalcogenides, the structure-property relationship of this compound remains unclear. Here we present a thorough study combining single-crystal X-ray diffraction and DFT calculations on SnS2 in the pressure range 0 < p < 20 GPa. The anisotropic compression of the unit cell is clearly linked to the van der Waals interactions between the S-Sn-S sandwich layers, as the compression mainly affects the interlayer distance. This compression behavior is coincidal with the compression of other well-known layered compounds (graphite and boron nitride) but differs significantly from the compression of other MS2 compounds, making it clear that SnS2 presents a unique and interesting case in the field of metal dichalcogenides. The compression leads to a significant increase in S...S interlayer interaction which in turn results in a change in the electronic structure, documented through DFT band structure calculations. The calculated narrowing of the band gap is supported by a significant, reversible color change of the single crystal. At 20 GPa, the size of the band gap has decreased from 2.15 to 0.88 eV, and band gap closure is predicted to occur at 33 GPa. PMID- 26820717 TI - The Effect of Widowhood on Parent-Child Relationships in Korea: Do Parents' Filial Expectations and Geographic Proximity to Children Matter? AB - Although previous research based on data from the U.S. suggests that parents' widowhood is associated with increased emotional support from children, little is known about the impact of late-life widowhood on intergenerational relationships in other cultures. Using data of Korean older adults, this paper examined: (1) the effect of widowhood on both positive and negative aspects of parent-child relationships and (2) whether these effects are moderated by older adults' expectations about children's filial responsibilities and the geographic proximity to their children. Analyses are based on data from the Hallym Aging Study, a stratified multi-stage probability sample of older adults living in the cities of Seoul and Chuncheon in Korea. Compared to married older adults, widowed persons in this sample reported higher levels of ambivalence, lower levels of positive interactions, and higher levels of negative interactions with their children. Parents' notion about filial responsibilities did not have a significant moderating effect, whereas geographic proximity to children was a significant moderator. Findings suggest that widowhood is associated with greater strain in intergenerational relationships in Korea. Helping widowed older adults forge constructive relationships with their children may enhance both bereaved older adults' and their children's well-being in this cultural milieu. PMID- 26820718 TI - Prevalence of laparoscopic surgical treatment and its clinical outcomes in patients with familial adenomatous polyposis in Japan. AB - BACKGROUND: Laparoscopic surgery is becoming the preferred technique for most colorectal interventions. This study aimed to clarify the time trend of surgical treatment for familial adenomatous polyposis (FAP) and its relevance to clinical outcomes in Japan over a 13-year period. METHODS: This was a multicenter retrospective cohort study comprising 23 specialist institutions for colorectal disease and a cohort of 282 FAP patients who underwent total colectomy or proctocolectomy during 2000-2012. Patient clinical backgrounds and surgical outcomes were compared between the first and second halves of the study period. RESULTS: The proportion of surgical types adopted over the entire study period was 46, 21, 30, and 3 % for ileoanal anastomosis (IAA), ileoanal canal anastomosis, ileorectal anastomosis, and permanent ileostomy, respectively. FAP patients undergoing laparoscopic surgery have increased since 2008 and reached 74 % in the past 3 years. In particular, the number of patients undergoing laparoscopic proctocolectomy with IAA increased approximately four-fold from the first to the second half of the study period. A laparoscopic approach was increasingly used in patients with coexisting colorectal malignancies. Despite this trend, surgical results of the laparoscopic approach between the two study periods showed similar morbidity, pouch operation and stoma closure completion rates. No postoperative mortality was observed in this series, and laparoscopic surgery was comparable to open surgery in terms of stoma closure rate, incidence of intra-abdominal/abdominal desmoid tumors, and postoperative survival rate in both study periods. CONCLUSION: Laparoscopic approach is increasingly being adopted for prophylactic FAP surgery in Japan and may provide clinically acceptable practical outcomes. PMID- 26820719 TI - Colorectal cancer in young patients: is it a distinct clinical entity? AB - BACKGROUND: The incidence of colorectal cancer in young patients is increasing. It remains unclear if the disease has unique features in this age group. METHODS: This was a single-center, retrospective cohort study which included patients diagnosed with colorectal cancer at age <=40 years in 1997-2013 matched 1:2 by year of diagnosis with consecutive colorectal cancer patients diagnosed at age >50 years during the same period. Patients aged 41-50 years were not included in the study, to accentuate potential age-related differences. Clinicopathological characteristics, treatment, and outcome were compared between groups. RESULTS: The cohort included 330 patients, followed for a median time of 65.9 months (range 4.7-211). Several significant differences were noted. The younger group had a different ethnic composition. They had higher rates of family history of colorectal cancer (p = 0.003), hereditary colorectal cancer syndromes (p < 0.0001), and inflammatory bowel disease (p = 0.007), and a lower rate of polyps (p < 0.0001). They were more likely to present with stage III or IV disease (p = 0.001), angiolymphatic invasion, signet cell ring adenocarcinoma, and rectal tumors (p = 0.02). Younger patients more frequently received treatment. Young patients had a worse estimated 5-year disease-free survival rate (57.6 vs. 70 %, p = 0.039), but this did not retain significance when analyzed by stage (p = 0.092). Estimated 5-year overall survival rates were 59.1 and 62.1 % in the younger and the control group, respectively (p = 0.565). CONCLUSIONS: Colorectal cancer among young patients may constitute a distinct clinical entity. Further research is needed to validate our findings and define the optimal approach in this population. PMID- 26820721 TI - [Basophilic granulocytes and autoimmune diseases. Can basophilic granulocytes modulate B-cell functions in systemic lupus erythematosus?]. AB - BACKGROUND: B-cells play an important role in the pathogenesis of systemic lupus erythematosus (SLE); however, many other cell types are also involved in disease development. In a murine lupus model it was demonstrated that basophils are indispensable for the development of lupus symptoms. AIM: This study investigated whether there is evidence for a relevant interaction between B-cells and basophils under physiological and pathological conditions. MATERIAL AND METHODS: A selective review of the literature was performed and some preliminary data about the interaction of basophils and B-cells are reported in this article. For the experiments, isolated B-cells were cultured in vitro in the presence or absence of basophils and B-cell survival, proliferation, plasma cell development and antibody production were determined. RESULTS: Data from the literature show that there is evidence for an interaction between basophils and B-cells in a murine model. Our investigations confirmed that human basophils also support the survival and proliferation of B-cells. Furthermore, plasma cell differentiation and antibody production, most importantly IgG secretion, are enhanced. First experimental ex vivo analyses of basophils from SLE patients demonstrate that these cells exhibit a higher activation level compared to basophils from healthy controls. DISCUSSION: In summary, previously published data and our own data demonstrate that there is an interaction between human basophils and B-cells. A better understanding of the role of basophils in the pathogenesis of SLE could lead to the development of new therapeutic strategies. PMID- 26820720 TI - On the Utility of Short Echo Time (TE) Single Voxel 1H-MRS in Non-Invasive Detection of 2-Hydroxyglutarate (2HG); Challenges and Potential Improvement Illustrated with Animal Models Using MRUI and LCModel. AB - Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are frequently found in brain tumors, and the resulting onco-metabolite, 2-hydroxyglutarate (2HG), has been suggested to be a potential diagnostic and prognostic biomarker of the diseases. Indeed, recent studies have demonstrated the feasibility of non invasively detecting 2HG by using proton magnetic resonance spectroscopy (1H MRS). Due to severe spectral overlaps of 2HG with its background metabolites and spectral baselines, however, the majority of those previous studies employed spectral editing methods with long echo times (TEs) instead of the most commonly used short TE approach with spectral fitting. Consequently, the results obtained with spectral editing methods may potentially be prone to errors resulting from substantial signal loss due to relaxation. Given that the spectral region where the main signal of 2HG resides is particularly sensitive to spectral baseline in metabolite quantification, we have investigated the impact of incorporating voxel specifically measured baselines into the spectral basis set on the performance of the conventional short TE approach in 2HG detection in rodent models (Fisher 344 rats; n = 19) of IDH1/2 mutant-overexpressing F98 glioma at 9.4T. Metabolite spectra were acquired (SPECIAL sequence) for a tumor region and the contralateral normal region of the brain for each animal. For the estimation of spectral baselines metabolite-nulled spectra were obtained (double-inversion-recovery SPECIAL sequence) for each individual voxels. Data were post-processed with and without the measured baselines using MRUI and LCModel-the two most widely used data post-processing packages. Our results demonstrate that in-vivo detection of 2HG using the conventional short TE approach is challenging even at 9.4T. However, incorporation of voxel-specifically measured spectral baselines may potentially improve its performance. Upon more thorough validation in a larger number of animals and more importantly in human patients, the potential utility of the proposed short TE acquisition with voxel-specific baseline measurement approach in 2HG detection may need to be considered in the study design. PMID- 26820722 TI - Circulating leptin level in rheumatoid arthritis and its correlation with disease activity: a meta-analysis. AB - OBJECTIVE: This study aimed to evaluate the relationship between the circulating serum leptin level and rheumatoid arthritis (RA) and to establish a correlation between serum leptin levels and RA activity. METHODS: We searched the PUBMED, EMBASE, and Cochrane databases. A meta-analysis was performed, comparing the serum/plasma leptin levels in patients with RA and healthy controls. Correlation coefficients between serum leptin level and either disease activity score 28 (DAS28) or C-reactive protein (CRP) in RA patients were also examined. RESULTS: Thirteen studies with a total of 648 RA patients and 426 controls were included in this meta-analysis. Circulating leptin level was significantly higher in the RA group than in the control group (SMD = 1.056, 95 % CI = 0.647-1.465, p = 4.2 * 10-7). In addition, stratification by ethnicity showed a significantly elevated leptin level in the RA group in Caucasian, Turkish, and Arab populations (SMD = 0.813, 95 % CI = 0.137-1.490, p = 0.018, SMD = 0.981, 95 % CI = 0.307-1.655, p = 0.004, and SMD = 1.469, 95 % CI = 0.443-2.495, p = 0.005 respectively). A meta analysis of correlation coefficients showed a small but significantly positive correlation between the circulating leptin level and either DAS28 (correlation coefficient = 0.275, 95 % CI = 0.076-0.452, p = 0.007) or CRP (correlation coefficient = 0.274, 95 % CI = 0.068-0.458, p = 0.010). CONCLUSIONS: Our meta analysis demonstrated that the circulating leptin level is significantly higher in patients with RA and that a small but significantly positive correlation exists between leptin levels and RA activity. PMID- 26820723 TI - [Antinuclear antibodies without connective tissue disease : Antibodies against LEDGF/DSF70]. AB - Testing for antinuclear antibodies (ANA) by the indirect immunofluorescence test (IFT) is regarded as a fundamental serological screening method for diagnosing connective tissue diseases (CTD). In the case of a negative result exclusion of certain CTDs is indicated, especially systemic lupus erythematosus, and a positive ANA result is the starting point for further tests aimed at finding disease-specific autoantibodies. The recently discovered antibodies against lens epithelium-derived growth factor (LEDGF/DSF70) deviate from the normal interpretation pattern in ANA diagnostics. These antibodies give rise to a characteristic dense fine speckled (DSF) immunofluorescence pattern in IFT and target the ubiquitously expressed nuclear stress protector protein LEDGFp75. They can be detected, sometimes in high titers, not only in patients with diverse disorders of the skin or eyes and with neoplasms but also in persons with relatively mild or unspecific complaints and even in apparently healthy individuals; however, they are less frequent in CTD. These anti-LEDGF antibodies can be found in all age groups with a tendency to a higher prevalence in younger people and the frequency does not increase in advanced age. The vast majority of anti-LEDGF carriers are female. The CTDs with isolated anti-LEDGF antibodies, i. e. unaccompanied by autoantibodies typical for the respective CTD, are extremely rare. Detection of ANA exclusively with a DSF immunofluorescence pattern and confirmed by a specific anti-LEDGF binding assay, does not therefore indicate the presence of CTD but is indicative of exclusion of systemic lupus erythematosus, systemic sclerosis and an ANA-associated overlap syndrome, similar to a completely negative ANA result. PMID- 26820724 TI - Mutations in Mtr4 Structural Domains Reveal Their Important Role in Regulating tRNAiMet Turnover in Saccharomyces cerevisiae and Mtr4p Enzymatic Activities In Vitro. AB - RNA processing and turnover play important roles in the maturation, metabolism and quality control of a large variety of RNAs thereby contributing to gene expression and cellular health. The TRAMP complex, composed of Air2p, Trf4p and Mtr4p, stimulates nuclear exosome-dependent RNA processing and degradation in Saccharomyces cerevisiae. The Mtr4 protein structure is composed of a helicase core and a novel so-called arch domain, which protrudes from the core. The helicase core contains highly conserved helicase domains RecA-1 and 2, and two structural domains of unclear functions, winged helix domain (WH) and ratchet domain. How the structural domains (arch, WH and ratchet domain) coordinate with the helicase domains and what roles they are playing in regulating Mtr4p helicase activity are unknown. We created a library of Mtr4p structural domain mutants for the first time and screened for those defective in the turnover of TRAMP and exosome substrate, hypomodified tRNAiMet. We found these domains regulate Mtr4p enzymatic activities differently through characterizing the arch domain mutants K700N and P731S, WH mutant K904N, and ratchet domain mutant R1030G. Arch domain mutants greatly reduced Mtr4p RNA binding, which surprisingly did not lead to significant defects on either in vivo tRNAiMet turnover, or in vitro unwinding activities. WH mutant K904N and Ratchet domain mutant R1030G showed decreased tRNAiMet turnover in vivo, as well as reduced RNA binding, ATPase and unwinding activities of Mtr4p in vitro. Particularly, K904 was found to be very important for steady protein levels in vivo. Overall, we conclude that arch domain plays a role in RNA binding but is largely dispensable for Mtr4p enzymatic activities, however the structural domains in the helicase core significantly contribute to Mtr4p ATPase and unwinding activities. PMID- 26820725 TI - Partial Replacement of Ground Corn with Glycerol in Beef Cattle Diets: Intake, Digestibility, Performance, and Carcass Characteristics. AB - The objective of this study was to evaluate the effects of replacing dry ground corn with crude glycerol on intake, apparent digestibility, performance, and carcass characteristics of finishing beef bulls. A completely randomized block design experiment with 25 d for adaptation and 100 d for data collection was conducted, in which 3,640 Nellore bulls (367 +/- 36.8 kg; 18 +/- 3 mo) were blocked by body weight and assigned to 20 pens. Bulls were randomly assigned to one of four treatments: 0, 5, 10, and 15% (dry matter basis) of crude glycerol in the diet. Initially, 20 bulls were slaughtered to serve as a reference to estimate initial empty body weight, which allowed for carcass gain calculation. Bulls were weighed at the beginning, at two-thirds, and at the end of the experiment for performance calculations. Carcass measurements were obtained by ultrasound. Fecal output was estimated using indigestible neutral detergent fiber as an internal marker. Data were analyzed using the mixed procedures in SAS 9.2 (SAS Institute Inc., Cary, NC). Intake of dry matter, organic matter, and neutral detergent fiber decreased linearly (P < 0.05) with crude glycerol inclusion. However, crude glycerol levels did not affect (P > 0.05) intakes of crude protein, non-fiber carbohydrates, and total digestible nutrients. Digestibility of dry matter, organic matter, neutral detergent fiber, and total digestible nutrients increased quadratically (P < 0.05) with the inclusion of crude glycerol in the diet. Crude glycerol inclusion did not change the intake of digestible dry matter, average daily gain, final body weight, carcass gain, carcass dressing, gain-to-feed ratio, Longissimus thoracis muscle area, and back and rump fat thicknesses (P > 0.05). These results suggest that crude glycerol may be included in finishing beef diets at levels up to 15% without impairing performance and carcass characteristics. PMID- 26820726 TI - Quality of Care for Patients with Chronic Respiratory Diseases: Data for Accreditation Plan in Primary Healthcare. AB - There are scarce reports in the literature on factors affecting the assessment of the quality of care for patients with chronic respiratory diseases. Such information is relevant in the accreditation process on implementing the healthcare. The study group consisted of 133 adult patients with chronic respiratory diseases and 125 adult patients with chronic non-respiratory diseases. In the present study, the level of satisfaction from healthcare provided by the primary healthcare unit, disease acceptance, quality of life, health behaviors, and met needs were examined, as well as associations between variables with the use of correspondence analysis. The results are that in patients with chronic respiratory diseases an increase in satisfaction depends on the improvement of well-being in the mental sphere. The lack of problems with obtaining a referral to a specialist and a higher level of fulfilled needs also have a positive effect. Additionally, low levels of satisfaction should be expected in those patients with chronic respiratory diseases who wait for an appointment in front of the office for a long time, report problems with obtaining a referral to additional tests, present a low level of health behaviors, and have a low index of benefits. PMID- 26820727 TI - Spirometry or Body Plethysmography for the Assessment of Bronchial Hyperresponsiveness? AB - Methacholine testing is one of the standard tools for the diagnosis of mild asthma, but there is little information about optimal outcome measures. In this study a total of 395 college students were tested by the ATS dosimeter protocol for methacholine testing, with minor modification. Body plethysmography and spirometry were measured after each inhalation step. The end-of-test-criteria were (i) decrease in forced expiratory volume in 1 s (FEV1) of >= 20 % and (ii) doubling of specific airway resistance and its increase to >= 2.0 kPa?s. The results were expressed by receiver operating characteristic (ROC) plots using questionnaire answers as a reference. The areas under the ROC curves were iteratively calculated for a wide range of thresholds for both measures. We found that ROC plots showed maximal sensitivities of about 0.5-0.6 for FEV1 and about 0.7 for specific airway conductance (sGt), with similar specificities of about 0.7-0.8 taking questions with the known high specificity as references. Accordingly, larger maximal areas under the ROC curve were observed for body plethysmography, but the differences were small. A decrease in FEV1 of about 15 % and a decrease of sGt of about 60 % showed the largest areas under the ROC curves. In conclusion, body plethysmography yielded better sensitivity than spirometry, with similar specificity. However, replacing the common spirometric criterium for a positive test (20 % decrease in FEV1 from baseline) by the optimal body plethysmographic criterium would result in an increase of false positive tests from about 4 to 8 % in healthy young adults. PMID- 26820728 TI - Swelling of Erectile Nasal Tissue Induced by Human Sexual Pheromone. AB - Most chemically mediated sexual communication in humans remains uncharacterized. Yet the study of sexual communication is decisive for understanding sexual behavior and evolutive mechanisms in our species. Here we provide the evidence to consider 4,16-androstadien-3-one (AND) as a man's sexual pheromone. Our experiment provides support for the physiological effect of AND on nasal airway resistance (Rna) in women, as assessed by anterior rhinomanometry. We found that AND administration increased the area of turbinate during the ovulatory phase, resulting in an increase of Rna. Thus, we discovered that minute amounts of AND, acting through neuroendocrine brain control, regulate Rna and consequently affect the sexual physiology and behavior. Fascinatingly, this finding provides the evidence of the preservation of chemosexual communication in humans, which it has been largely neglected due to its unconscious perception and concealed nature. Therefore, chemical communication is a plesiomorphic evolutive phenomenon in humans. PMID- 26820729 TI - Prosthetic Rehabilitation of Patients After Surgical Treatment of Maxillary Tumors with Respect to Upper Airway Protection. AB - As a consequence of surgical treatment of maxillary tumors, a connection between oral and nasal cavities is formed, which leads to serious functional disorders, manifested by inability to normally ingest food, proper speech articulation, and to respiratory route disorders and upper airway inflammation. These morphological and functional disorders are intensified by adjunctive radio- or chemotherapy. The aim of this paper is to present different possible methods of rehabilitation, including application of interim obturators and individually planned prosthetic restorations to improve respiratory efficiency in patients after extensive maxillary resections. In the course of prosthetic treatment, cooperation with the laryngologist to consider every aspect of chronic paranasal sinusitis, accompanied by concurrent inflammation of oral, nasal, or laryngeal mucous membranes, was of paramount importance. Based on the quality of life questionnaire, used in this study, evident improvement in the masticatory efficiency, speech articulation, and respiration was observed. Particularly good effects were obtained in edentulous patients, in whom implant-prosthetic treatment was possible to apply. Comprehensive and multidisciplinary care of postoperative patients greatly contributes to their better quality of life and facilitates their return to prior living conditions, as well as to occupational and family lives. PMID- 26820730 TI - Molecular Characteristics of Influenza Virus Type B Lineages Circulating in Poland. AB - From the time of the Hong Kong pandemic of 1968-1969, vaccines against influenza are trivalent, containing two subtypes of influenza type A: A/H1N1/ and A/H3N2/, and influenza type B. In 1980, circulation of the new Yamagata and Victoria lineages of influenza B virus was noted. Since both lineages have continued to circulate, the second lineage of influenza B was included into the trivalent vaccine as of the 2013/2014 epidemic season. In Poland, co-circulation of influenza type A and B has been registered over many seasons, although type A has predominated. According to the ACIP recommendations, quadrivalent vaccines against influenza are administered in some continents due to circulation of the B Yamagata and B-Victoria lineages. Currently, only trivalent vaccines against influenza are available in Poland. The aim of the present research was to determine which of the two influenza type B lineages, or possibly both, would be isolated in Poland. The study was conducted with the use of RT-PCR. Generally, in the 2014/2015 epidemic season in Poland, circulation of type B virus was confirmed in 34 % of influenza cases. A total of 89 specimens of influenza B were tested, including co-infections of influenza B with influenza A subtypes: A/H1N1/pdm09 and A/H3N2/. The findings were that only lineage B-Yamagata circulates in the Polish population. Therefore, vaccines available on the Polish market do not require the introduction of a fourth component. PMID- 26820731 TI - Sclerostin in Obstructive Sleep Apnea. AB - Sclerostin, a glycoprotein involved in vascular calcification, could play a role in cardiovascular disorders. Obstructive sleep apnea (OSA) is frequently associated with cardiovascular comorbidities. Thus, in this study we set out to assess the level of sclerostin in patients with OSA. Sclerostin was evaluated in the serum by ELISA method in 106 patients (43 women) with OSA of the mean age of 55 +/- 10 years, BMI of 33.1 +/- 7.9 kg/m(2), and apnea/hypopnea index (AHI) of 29.7 +/- 18.9. There were 76 (72 %) patients with cardiovascular comorbidities in the OSA group. The results were compared with those in 49 healthy control subjects. We found that the level of sclerostin was higher in the female OSA patients than that in female controls (80.1 +/- 36.5 pg/ml vs. 61.4 +/- 24.1 pg/ml; p < 0.05) and it correlated with AHI (rs = 0.32, p < 0.01) and desaturation index (rs = 0.34, p < 0.01). Further, in OSA women with cardiovascular comorbidities, sclerostin was higher than in women without such comorbidities (87.0 +/- 37.4 pg/ml vs. 57.3 +/- 22.1 pg/ml; p < 0.05). In men, there were no differences in the serum sclerostin level between the OSA and control subjects, nor was there any relationship with cardiovascular diseases. In conclusion, increased serum sclerostin coincides with the severity of OSA and its cardiovascular sequelae in female patients. PMID- 26820732 TI - Atherosclerotic Vessel Changes in Sarcoidosis. AB - Sarcoidosis is a systemic granulomatous disease. Atherosclerosis is a chronic inflammatory vessel disease. The aim of our present study was to investigate whether sarcoidosis could be associated with increased risk of atherosclerotic vessel changes. Angiological analysis and blood tests were performed in 71 sarcoidosis patients and 12 matched controls in this prospective cross-sectional study. Specifically, angiological measurements comprised ankle brachial index (ABI), central pulse wave velocity (cPWV), pulse wave index (PWI), and duplex sonography of central and peripheral arteries. Sarcoidosis activity markers (angiotensin converting enzyme, soluble interleukin-2 receptor) and cardiovascular risk parameters such as cholesterol, lipoprotein(a), C-reactive protein, interleukin 6, fibrinogen, d-dimer, and blood count were analyzed in blood. We found no relevant differences in ABI, cPWV, and plaque burden between the sarcoidosis and control groups (1.10 +/- 0.02 vs. 1.10 +/- 0.02, 6.7 +/- 0.5 vs. 6.1 +/- 1.2, 53.7 % vs. 54.5 %, respectively). However, PWI was significantly higher in sarcoidosis patients (146.2 +/- 6.8) compared with controls (104.9 +/- 8.8), irrespectively of the activity of sarcoidosis and immunosuppressive medication. Except for increased lipoprotein(a) and d-dimer in sarcoidosis, the remaining cardiovascular markers were similar in both groups. We conclude that sarcoidosis is associated with increased pulse wave index, which may indicate an early stage of atherosclerosis. PMID- 26820733 TI - Asthma and COPD: Similarities and Differences in the Pathophysiology, Diagnosis and Therapy. AB - Asthma and chronic obstructive pulmonary disease (COPD) are two of the most common chronic lung diseases worldwide. Distinguishing between these different pulmonary diseases can be difficult in practice because of symptomatic similarities. A definitive diagnosis is essential for correct treatment. This review article presents the different symptoms of these two chronic inflammatory lung diseases following a selective search of the PubMed database for relevant literature published between 1996 and 2012. While cough occurs in both diseases, asthmatics often have a dry cough mainly at night, which is often associated with allergies. In contrast, COPD is usually caused by years of smoking. Paroxysmal dyspnea, which occurs in asthma, is characterized by shortness of breath, while in COPD it occurs during physical exertion in early stages and at rest in later stages of the disease. Asthma often begins in childhood or adolescence, whereas COPD occurs mainly in smokers in later life. It is possible to live with asthma into old age, whereas the life expectancy of patients with COPD is significantly limited. Currently, there is no general curative treatment for either disorder. PMID- 26820734 TI - Concurrent Validity and Reliability of a New Balance Scale Used in Older Adults. AB - Adults over the age of 70 are at risk of falling. Various balance tests have been developed to identify balance dysfunctions. Their disadvantages including ceiling effects and low sensitivity and duration led to the development of a new balance test. The present study was conducted to determine the concurrent validity, reliability, sensitivity, and specificity of the Zur Balance Scale (ZBS). In this descriptive, cross-sectional study, 76 senior adults were recruited from an independent senior living community and were administered the Berg Balance Scale (BBS) and the ZBS. The BBS was used as the standard of comparison. The ZBS includes head movements and time to maintain to balance. All the subjects completed the tests. Concurrent validity was r = 0.782 (p < 0.0001). The ZBS had high intra-test (0.897) and inter-test (0.934) correlation coefficients. Its sensitivity was 60 % and specificity 91 % for identifying falls. The dynamic portions of the ZBS capture the integration of the visual, vestibular, and somatosensory systems, as it mimics dynamic spatial aspects of daily activities. We conclude that the ZBS is reliable compared with BBS. It is a simple, easy to administer test that may predict future risk of falls. PMID- 26820735 TI - Influence of Body Shape Composition on Respiratory Function in Adult Women. AB - The purpose of the study was to evaluate the influence of body size and shape, and of fat distribution on respiratory functions in adult women. The sample consisted of 107 women aged 17-82 years. Height, weight, chest, waist and hip circumferences, abdominal, and subscapular and triceps skinfolds were examined. The BMI and WHR were calculated. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), maximal expiratory flow (MEF75), forced expiratory time (FET) were used as measures of respiratory function. Positive correlations were found between z-scores of height and VC, FEV1, FVC, between WHR and VC, and between circumference and FET. Negative correlations were found between z-scores of BMI and VC, FEV1, between subscapular skinfold and VC, FEV1, FVC and between abdominal skinfold and VC. Stepwise multiple regression analysis showed that traits of body size and shape mostly influenced VC (32 %) and FVC (31 %). Body height and WHR significantly affected VC, while height and subscapular skinfold affected FVC. A significant association between fat distribution described by BMI, WHR, and skinfold thickness and respiratory parameters was observed. These results confirm a complex effect of body size and shape, and of fat distribution on respiratory function. PMID- 26820736 TI - Pancreatic ductal hyperplasia/dysplasia with obstructive chronic pancreatitis: an association with reduced pancreatic weight in type 1 diabetes. PMID- 26820737 TI - Semantic Factors Predict the Rate of Lexical Replacement of Content Words. AB - The rate of lexical replacement estimates the diachronic stability of word forms on the basis of how frequently a proto-language word is replaced or retained in its daughter languages. Lexical replacement rate has been shown to be highly related to word class and word frequency. In this paper, we argue that content words and function words behave differently with respect to lexical replacement rate, and we show that semantic factors predict the lexical replacement rate of content words. For the 167 content items in the Swadesh list, data was gathered on the features of lexical replacement rate, word class, frequency, age of acquisition, synonyms, arousal, imageability and average mutual information, either from published databases or gathered from corpora and lexica. A linear regression model shows that, in addition to frequency, synonyms, senses and imageability are significantly related to the lexical replacement rate of content words-in particular the number of synonyms that a word has. The model shows no differences in lexical replacement rate between word classes, and outperforms a model with word class and word frequency predictors only. PMID- 26820738 TI - Inhibition of Prostaglandin Reductase 2, a Putative Oncogene Overexpressed in Human Pancreatic Adenocarcinoma, Induces Oxidative Stress-Mediated Cell Death Involving xCT and CTH Gene Expressions through 15-Keto-PGE2. AB - Prostaglandin reductase 2 (PTGR2) is the enzyme that catalyzes 15-keto-PGE2, an endogenous PPARgamma ligand, into 13,14-dihydro-15-keto-PGE2. Previously, we have reported a novel oncogenic role of PTGR2 in gastric cancer, where PTGR2 was discovered to modulate ROS-mediated cell death and tumor transformation. In the present study, we demonstrated the oncogenic potency of PTGR2 in pancreatic cancer. First, we observed that the majority of the human pancreatic ductal adenocarcinoma tissues was stained positive for PTGR2 expression but not in the adjacent normal parts. In vitro analyses showed that silencing of PTGR2 expression enhanced ROS production, suppressed pancreatic cell proliferation, and promoted cell death through increasing 15-keto-PGE2. Mechanistically, silencing of PTGR2 or addition of 15-keto-PGE2 suppressed the expressions of solute carrier family 7 member 11 (xCT) and cystathionine gamma-lyase (CTH), two important providers of intracellular cysteine for the generation of glutathione (GSH), which is widely accepted as the first-line antioxidative defense. The oxidative stress-mediated cell death after silencing of PTGR2 or addition of 15-keto-PGE2 was further abolished after restoring intracellular GSH concentrations and cysteine supply by N-acetyl-L-cysteine and 2-Mercaptomethanol. Our data highlight the therapeutic potential of targeting PTGR2/15-keto-PGE2 for pancreatic cancer. PMID- 26820739 TI - Right heart chamber geometry and tricuspid annulus morphology in patients undergoing mitral valve repair with and without tricuspid valve annuloplasty. AB - According to current recommendations, patients could benefit from tricuspid valve (TV) annuloplasty at the time mitral valve (MV) surgery if tricuspid regurgitation is severe or if tricuspid annulus (TA) dilatation is present. Therefore, an accurate pre-operative echocardiographic study is mandatory for left but also for right cardiac structures. Aims of this study are to assess right atrial (RA), right ventricular (RV) and TA geometry and function in patients undergoing MV repair without or with TV annuloplasty. We studied 103 patients undergoing MV surgery without (G1: 54 cases) or with (G2: 49 cases) concomitant TV annuloplasty and 40 healthy subjects (NL) as controls. RA, RV and TA were evaluated by three-dimensional (3D) transthoracic echocardiography. Comparing the pathological to the NL group, TA parameters and 3D right chamber volumes were significantly larger. RA and RV ejection fraction and TA% reduction were lower in pathological versus NL, and in G2 versus G1. In pathological patients, TA area positively correlated to systolic pulmonary pressure and negatively with RV and RA ejection fraction. Patients undergoing MV surgery and TV annuloplasty had an increased TA dimensions and a more advanced remodeling of right heart chambers probably reflecting an advanced stage of the disease. PMID- 26820740 TI - Assessment of left and right atrial 3D hemodynamics in patients with atrial fibrillation: a 4D flow MRI study. AB - Atrial fibrillation (AF) is associated with embolic stroke due to thrombus formation in the left atrium (LA). Based on the relationship of atrial stasis to thromboembolism and the marked disparity in pulmonary versus systemic thromboembolism in AF, we tested the hypothesis that flow velocity distributions in the left (LA) versus right atrium (RA) in patients with would demonstrate increased stasis. Whole heart 4D flow MRI was performed in 62 AF patients (n = 33 in sinus rhythm during imaging, n = 29 with persistent AF) and 8 controls for the assessment of in vivo atrial 3D blood flow. 3D segmentation of the LA and RA geometry and normalized velocity histograms assessed atrial velocity distribution and stasis (% of atrial velocities <0.2 m/s). Atrial hemodynamics were similar for RA and LA and significantly correlated (mean velocity: r = 0.64; stasis: r = 0.55, p < 0.001). RA and LA mean and median velocities were lower in AF patients by 15-33 % and stasis was elevated by 11-19 % compared to controls. There was high inter-individual variability in LA/RA mean velocity ratio (range 0.5-1.8) and LA/RA stasis ratio (range 0.7-1.7). Patients with a history of AF and in sinus rhythm showed most pronounced differences in atrial flow (reduced mean velocities, higher stasis in the LA). While there is no systematic difference in LA versus RA flow velocity profiles, high variability was noted. Further delineation of patient specific factors and/or regional atrial effects on the LA and RA flow velocity profiles, as well as other factors such as differences in procoagulant factors, may explain the more prevalent systemic versus pulmonary thromboembolism in patients with AF. PMID- 26820741 TI - Detection of Human Papillomavirus Infections at the Single-Cell Level. AB - OBJECTIVE: To explore the possibility of single-cell analysis of human papillomavirus (HPV) infection. METHODS: Two hundred and twenty cells were isolated by laser capture microdissection from formalin-fixed and paraffin embedded cervical tissue blocks from 8 women who had HPV DNA detected in their cervical swab samples. The number of type-specific HPV copies in individual cells was measured by quantitative polymerase chain reaction with and without a prior reverse transcription. The cells were assayed and counted for more than once if the corresponding swab sample was positive for >=2 HPV types. RESULTS: Infection with HPV16, HPV39, HPV51, HPV52, HPV58, HPV59 and HPV73 was detected in 12 (5.5%) of 220, 3 (9.4%) of 32, 3 (5.8%) of 52, 11 (22.9%) of 48, 9 (18.8%) of 48, 3 (9.4%) of 32 and none of 20 cells, respectively. The numbers of HPV genome copies varied widely from cell to cell. The coexistence of multiple HPV types was detected in 6 (31.6%) of 19 positive cells from 1 of the 6 women who had 2 or 3 HPV types detected in their swab samples. CONCLUSION: Given the heterogeneity of HPV status in individual cells, further clarification of HPV infection at the single-cell level may refine our understanding of HPV-related carcinogenesis. PMID- 26820742 TI - Non-Maternal Infant Handling in Wild Formosan Macaques of Mount Longevity, Taiwan. AB - In this paper, we present quantitative data on how the social network and sex of infants influence allomothering behaviour among wild Formosan macaques, Macaca cyclopis. Using long-term field data collected from the Mount Longevity study site in Kaohsiung (Taiwan), we have tested relevant hypotheses incorporating data on age, rank and reproductive state of infant handlers, and the relationship between handlers and infants. The results support 2 major hypotheses, i.e. those of reciprocity and alliance formation. Nevertheless, neither could account for the observed occurrences of unrelated infant handling by dominant females. PMID- 26820743 TI - Influence of somatization and depressive symptoms on the course of pain within the first year after uncomplicated total knee replacement: a prospective study. AB - PURPOSE: Approximately 10-25 % of patients are reportedly dissatisfied with the results of bicondylar knee prosthesis implantation. The purpose of this study was to evaluate the effect of depressive symptoms and particularly somatization dysfunction on outcomes after total knee replacement (TKR). METHODS: One hundred fifty patients were enrolled in this prospective study. Pre-operatively, depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ 9) and somatization was assessed using the PHQ-15. The primary outcome measure was self-assessed knee function evaluated with the Knee Osteoarthritis Outcome Score (KOOS). Pain was measured on a numerical rating scale (NRS). The secondary outcome measures were the KOOS subscales and patient satisfaction. Intergroup differences were tested using an independent t-test. The odds ratio was used to determine the probability of an unsatisfactory outcome. RESULTS: At 12 months post-operatively, patients with depressive symptoms and particularly patients with somatization dysfunction usually had a significantly higher NRS score at rest and during activities, a lower knee function before and after surgery, and higher dissatisfaction. CONCLUSIONS: Psychopathologic factors, particularly somatization dysfunction, have an impact on TKR outcomes. Preoperative screening and concurrent treatment of the diagnosed psychological disorder may improve patient-perceived outcomes. PMID- 26820744 TI - Overview: the role of Propionibacterium acnes in nonpyogenic intervertebral discs. AB - Propionibacterium acnes (P. acnes), an important opportunistic anaerobic Gram positive bacterium, causes bone and joint infections, discitis and spondylodiscitis. Accumulated evidence suggested that this microbe can colonise inside intervertebral discs without causing symptoms of discitis. Epidemiological investigation shows that the prevalence ranges from 13 % to 44 %. Furthermore, colonisation by P. acnes inside nonpyogenic intervertebral discs is thought to be one pathogen causing sciatica, Modic changes and nonspecific low back pain. Specially, patients can attain significant relief of low back pain, amelioration of Modic changes and alleviation of sciatica after antibiotic therapy, indicating the role of P. acnes in these pathological changes. However, until now, there were hypotheses only to explain problems such as how P. acnes access intervertebral discs and what the exact pathological mechanism it employs during its latent infection period. In addition, research regarding diagnostic procedures and treatment strategies were also rare. Overall, the prevalence and possible pathological role that P. acnes plays inside nonpyogenic intervertebral discs is summarised in this paper. PMID- 26820747 TI - Curriculum reform: the more things change, the more they stay the same? PMID- 26820745 TI - Preliminary results of two surgical techniques in the treatment of recurrent patellar dislocation : Medial patellofemoral ligament reconstruction versus combined technique of vastus medialis advancement, capsular plasty and Roux Goldthwait procedure in treatment of recurrent patellar dislocation. AB - PURPOSE: Recurrent patellar dislocation is defined as a dislocation occurring more than once. There is no consensus as to the choice of operative technique for recurrent dislocation in adolescents. Recently, great importance has been attributed to MPFL reconstruction. The aim of this study is to evaluate the value of MPFL reconstruction (group A) in adolescents by comparing MPFL reconstruction with combined soft tissue proximal and distal alignment (group B). METHODS: MPFL reconstruction by means of Avikainen's technique was performed on 32 knees. Another 33 knees were subject to the techniques combining retinacular plasty, vastus medialis advancement, and Roux-Goldthwait procedure. The results were assed clinically (Lyscholm scale and the Kujala Anterior Knee Pain Scale) and using X-rays (axial and lateral knee view). Isokinetic assessment of the quadriceps and hamstring was performed. RESULTS: No statistically significant differences between the two groups were observed regarding the Lyscholm and Kujala scales, the presence of redislocation (9.3 % for group A versus 12.1 % for group B), apprehension test, abnormal patellofemoral angle, abnormal Caton index (p > 0.05). A statistically significant difference between the groups was observed regarding the rate of pain complaints, the incidence of an abnormal congruence angle, patellar medialization and deficits in the peak torque of the hamstring between the two angular velocities (p < 0.05). CONCLUSIONS: The redislocation rates risk is similar in both groups. However, a lower incidence of pain complaints in the group of patients with MPFL reconstruction favours the use of MPFL reconstruction as the first choice technique. LEVEL OF EVIDENCE: III. PMID- 26820746 TI - NINJA-OPS: Fast Accurate Marker Gene Alignment Using Concatenated Ribosomes. AB - The explosion of bioinformatics technologies in the form of next generation sequencing (NGS) has facilitated a massive influx of genomics data in the form of short reads. Short read mapping is therefore a fundamental component of next generation sequencing pipelines which routinely match these short reads against reference genomes for contig assembly. However, such techniques have seldom been applied to microbial marker gene sequencing studies, which have mostly relied on novel heuristic approaches. We propose NINJA Is Not Just Another OTU-Picking Solution (NINJA-OPS, or NINJA for short), a fast and highly accurate novel method enabling reference-based marker gene matching (picking Operational Taxonomic Units, or OTUs). NINJA takes advantage of the Burrows-Wheeler (BW) alignment using an artificial reference chromosome composed of concatenated reference sequences, the "concatesome," as the BW input. Other features include automatic support for paired-end reads with arbitrary insert sizes. NINJA is also free and open source and implements several pre-filtering methods that elicit substantial speedup when coupled with existing tools. We applied NINJA to several published microbiome studies, obtaining accuracy similar to or better than previous reference-based OTU-picking methods while achieving an order of magnitude or more speedup and using a fraction of the memory footprint. NINJA is a complete pipeline that takes a FASTA-formatted input file and outputs a QIIME-formatted taxonomy-annotated BIOM file for an entire MiSeq run of human gut microbiome 16S genes in under 10 minutes on a dual-core laptop. PMID- 26820748 TI - Undergraduate medical education programme renewal: a longitudinal context, input, process and product evaluation study. AB - The purpose of this study was to utilize the Context, Input, Process and Product (CIPP) evaluation model as a comprehensive framework to guide initiating, planning, implementing and evaluating a revised undergraduate medical education programme. The eight-year longitudinal evaluation study consisted of four phases compatible with the four components of the CIPP model. In the first phase, we explored the strengths and weaknesses of the traditional programme as well as contextual needs, assets, and resources. For the second phase, we proposed a model for the programme considering contextual features. During the process phase, we provided formative information for revisions and adjustments. Finally, in the fourth phase, we evaluated the outcomes of the new undergraduate medical education programme in the basic sciences phase. Information was collected from different sources such as medical students, faculty members, administrators, and graduates, using various qualitative and quantitative methods including focus groups, questionnaires, and performance measures. The CIPP model has the potential to guide policy makers to systematically collect evaluation data and to manage stakeholders' reactions at each stage of the reform in order to make informed decisions. However, the model may result in evaluation burden and fail to address some unplanned evaluation questions. PMID- 26820749 TI - Serum uric acid level and association with cognitive impairment and dementia: systematic review and meta-analysis. AB - Serum uric acid (sUA) level may be associated with cognitive impairment/dementia. It is possible this relationship varies with dementia subtype, particularly between vascular dementias (VaD) and Alzheimer's (AD) or Parkinson's disease (PDD)-related dementia. We aimed to present a synthesis of all published data on sUA and relationship with dementia/cognition through systematic review and meta analysis. We included studies that assessed the association between sUA and any measure of cognitive function or a clinical diagnosis of dementia. We pre-defined subgroup analyses for patients with AD, VaD, PDD, mild cognitive impairment (MCI), and mixed or undifferentiated. We assessed risk of bias/generalizability, and where data allowed, we performed meta-analysis to describe pooled measures of association across studies. From 4811 titles, 46 papers (n = 16,688 participants) met our selection criteria. Compared to controls, sUA was lower in dementia (SDM 0.33 (95%CI)). There were differences in association by dementia type with apparent association for AD (SDM -0.33 (95%CI)) and PDD (SDM -0.67 (95%CI)) but not in cases of mixed dementia (SDM 0.19 (95%CI)) or VaD (SDM -0.05 (95%CI)). There was no correlation between scores on Mini-Mental State Examination and sUA level (summary r 0.08, p = 0.27), except in patients with PDD (r 0.16, p = 0.003). Our conclusions are limited by clinical heterogeneity and risk of bias in studies. Accepting this caveat, the relationship between sUA and dementia/cognitive impairment is not consistent across all dementia groups and in particular may differ in patients with VaD compared to other dementia subtypes. PMID- 26820750 TI - Perceptions of Private Medical Practitioners on Tuberculosis Notification: A Study from Chennai, South India. AB - BACKGROUND: The Government of India declared TB as a notifiable disease in 2012. There is a paucity of information on the government's mandatory TB notification order from the perspective of private medical practitioners (PPs). OBJECTIVE: To understand the awareness, perception and barriers on TB notification among PPs in Chennai, India. METHODS: Total of 190 PPs were approached in their clinics by trained field staff who collected data using a semi-structured and pre-coded questionnaire after getting informed consent. The data collected included PPs' specialization, TB management practices, awareness about the TB notification order, barriers in its implementation and their suggestions to improve notification. RESULTS: Of 190 PPs from varied specializations, 138 (73%) had diagnosed TB cases in the prior three months, of whom 78% referred these patients to government facilities. Of 138 PPs, 73% were aware of the order on mandatory TB notification, of whom 46 (33%) had ever notified a TB case. Of 120 PPs, 63% reported reasons for not notifying TB cases. The main reasons reported for not notifying were lack of time (50%), concerns regarding patients' confidentiality (24%) and fear of offending patients (11%). Of 145 PPs, 76% provided feedback about information they felt uncomfortable reporting during notification. PPs felt most uncomfortable reporting patient's government-issued Aadhar number (77%), followed by patient's phone number (37%) and residential address (26%). The preferred means of notification was through mobile phone communication (24%), SMS (18%) and e-mail (17%). CONCLUSION: This study highlights that one-fourth of PPs were not aware of the TB notification order and not all those who were aware were notifying. While it is important to sensitize PPs on the importance of TB notification it is also important to understand the barriers faced by PPs and to make the process user-friendly in order to increase TB notification. PMID- 26820751 TI - Fat accumulation in differentiated brown adipocytes is linked with expression of Hox genes. AB - Homeobox (Hox) genes are involved in body plan of embryo along the anterior posterior axis. Presence of several Hox genes in white adipose tissue (WAT) and brown adipose tissue (BAT) is indicative of involvement of Hox genes in adipogenesis. We propose that differentiation inducing agents viz. isobutyl methyl-xanthine (IBMX), indomethacin, dexamethasone (DEX), triiodothyronine (T3) and insulin may regulate differentiation in brown adipose tissue through Hox genes. In vitro culture of brown fat stromalvascular fraction (SVF) in presence or absence of differentiation inducing agents was used for establishing relationship between fat accumulation in differentiated adipocytes and expression of Hox genes. Relative expression of Pref1, UCP1 and Hox genes was determined in different stages of adipogenesis. Presence or absence of IBMX, indomethacin and DEX during differentiation of proliferated pre-adipocytes resulted in marked differences in expression of Hox genes and lipid accumulation. In presence of these inducing agents, lipid accumulation as well as expression of HoxA1, HoxA5, HoxC4 &HoxC8 markedly enhanced. Irrespective of presence or absence of T3, insulin down regulates HoxA10. T3 results in over expression of HoxA5, HoxC4 and HoxC8 genes, whereas insulin up regulates expression of only HoxC8. Findings suggest that accumulation of fat in differentiated adipocytes is linked with expression of Hox genes. PMID- 26820752 TI - Human Leptospirosis Infection in Fiji: An Eco-epidemiological Approach to Identifying Risk Factors and Environmental Drivers for Transmission. AB - Leptospirosis is an important zoonotic disease in the Pacific Islands. In Fiji, two successive cyclones and severe flooding in 2012 resulted in outbreaks with 576 reported cases and 7% case-fatality. We conducted a cross-sectional seroprevalence study and used an eco-epidemiological approach to characterize risk factors and drivers for human leptospirosis infection in Fiji, and aimed to provide an evidence base for improving the effectiveness of public health mitigation and intervention strategies. Antibodies indicative of previous or recent infection were found in 19.4% of 2152 participants (81 communities on the 3 main islands). Questionnaires and geographic information systems data were used to assess variables related to demographics, individual behaviour, contact with animals, socioeconomics, living conditions, land use, and the natural environment. On multivariable logistic regression analysis, variables associated with the presence of Leptospira antibodies included male gender (OR 1.55), iTaukei ethnicity (OR 3.51), living in villages (OR 1.64), lack of treated water at home (OR 1.52), working outdoors (1.64), living in rural areas (OR 1.43), high poverty rate (OR 1.74), living <100m from a major river (OR 1.41), pigs in the community (OR 1.54), high cattle density in the district (OR 1.04 per head/sqkm), and high maximum rainfall in the wettest month (OR 1.003 per mm). Risk factors and drivers for human leptospirosis infection in Fiji are complex and multifactorial, with environmental factors playing crucial roles. With global climate change, severe weather events and flooding are expected to intensify in the South Pacific. Population growth could also lead to more intensive livestock farming; and urbanization in developing countries is often associated with urban and peri-urban slums where diseases of poverty proliferate. Climate change, flooding, population growth, urbanization, poverty and agricultural intensification are important drivers of zoonotic disease transmission; these factors may independently, or potentially synergistically, lead to enhanced leptospirosis transmission in Fiji and other similar settings. PMID- 26820753 TI - Fabrication of a Selective and Sensitive Sensor Based on Molecularly Imprinted Polymer/Acetylene Black for the Determination of Azithromycin in Pharmaceuticals and Biological Samples. AB - A new selective and sensitive sensor based on molecularly imprinted polymer/acetylene black (MIP/AB) was developed for the determination of azithromycin (AZM) in pharmaceuticals and biological samples. The MIP of AZM was synthesized by precipitation polymerization. MIP and AB were then respectively introduced as selective and sensitive elements for the preparation of MIP/AB modified carbon paste (MIP/ABP) electrode. The performance of the obtained sensor was estimated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. Compared with non-molecularly imprinted polymer (NIP) electrodes, NIP/ABP electrodes, and MIP-modified carbon paste electrodes, MIP/ABP electrode exhibited excellent current response toward AZM. The prepared sensor also exhibited good selectivity for AZM in comparison with structurally similar compounds. The effect of electrode composition, extraction parameters, and electrolyte conditions on the current response of the sensor was investigated. Under the optimized conditions, the prepared sensor showed two dynamic linear ranges of 1.0 * 10-7 mol L-1 to 2.0 * 10-6 mol L-1 and 2.0 * 10-6 mol L-1 to 2.0 * 10-5 mol L-1, with a limit of detection of 1.1 * 10-8 mol L-1. These predominant properties ensured that the sensor exhibits excellent reliability for detecting AZM in pharmaceuticals and biological fluids without the assistance of any separation techniques. The results were validated by the high-performance liquid chromatography-tandem mass spectrometry method. PMID- 26820754 TI - Neurology of Sepsis. AB - Sepsis is a systemic inflammatory response syndrome occurring secondary to infection and labeled severe when end organ dysfunction or tissue hypoperfusion transpires. Sepsis-associated mortality remains high among critically ill patients, with chronic disease and immunosuppression being the most common risk factors. Studies demonstrate that early recognition and treatment are vital to decreasing mortality. Some of the least understood effects of sepsis are the associated neurologic complications. The peripheral nervous system (PNS) has gained most consideration and thought, largely due to dependence on mechanical ventilation. Central nervous system (CNS) complications related to sepsis have only more recently gained attention but continue to go unnoticed. Aside from the clinical examination, electroencephalography (EEG) is a sensitive tool for prognostication or uncovering non-convulsive seizures in encephalopathic patients. Further studies are needed to further define the urgency of a prevention and treatment plan for the deleterious effects of sepsis on the PNS and CNS. PMID- 26820755 TI - Recommendations for Solid Organ Transplantation for Transplant Candidates With a Pretransplant Diagnosis of Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma and Melanoma: A Consensus Opinion From the International Transplant Skin Cancer Collaborative (ITSCC). AB - Advancements in solid organ transplantation successfully extend the lives of thousands of patients annually. The tenet of organ stewardship aims to prevent the futile expenditure of scarce donor organs in patient populations with high mortality risk, to the detriment of potential recipients with greater predicted life expectancy. The development of skin cancer posttransplantation portends tremendous morbidity, adversely affecting quality of life for many transplant recipients. This special article, provided by of members of the International Transplant Skin Cancer Collaborative (ITSCC), will provide the transplant professional with a consensus opinion and recommendations as to an appropriate wait period pretransplantation for transplant candidates with a history of either cutaneous squamous cell carcinoma, malignant melanoma, or Merkel cell carcinoma. PMID- 26820757 TI - Preclinical studies and clinical evaluation of compounds from the genus Epimedium for osteoporosis and bone health. AB - The morbidity and mortality associated with fractures due to osteoporosis or "porous bone" contributes significantly to global healthcare costs and will increase exponentially with ageing populations. In menopausal women, the onset of menopause and rapid estrogen withdrawal leads to osteoporotic fractures. Healthy bone requires the coordinated remodeling function of osteoclasts, osteoblasts, and osteocytes in the basic bone multicellular unit, regulated by estrogen, RANKL/OPG, ROS, growth factors, and other kinase signaling pathways. Anti osteoporotic drugs in current use such as hormone replacement therapy, selective estrogen receptor modulators, and bisphosphonates are designed to target these pathways, but all have their limitations. Extracts of the dried aerial parts of the traditional Chinese medicinal plant Epimedium (Berberidaceae) has long been used for bone health. Some nine Epimedium prenylflavonoid compounds have been reported to target estrogen signaling and other bone morphogenesis pathways in mesenchymal stem cell, osteoblast, and osteoclast cell lineages. Epimedium prenylflavonoids and enriched extracts can exert beneficial effects on bone health in estrogen-deficient and other osteoporosis animal models. The development of sensitive and rapid mass chromatographic techniques to quantify compounds extracted from Epimedium, including icariin and icaritin, has been used to standardize production and to study the pharmacokinetics and metabolism of Epimedium in animal models and humans. Recent clinical trials have reported positive effects on bone health, suggesting that compounds or extracts of Epimedium have the potential to be developed as agents, alone or in combination with other drugs, to prevent or delay the onset of osteoporosis and reduce the risk of hip fractures. PMID- 26820756 TI - alphaB-crystallin: Portrait of a malignant chaperone as a cancer therapeutic target. AB - alphaB-crystallin is a widely expressed member of the small heat shock protein family that protects cells from stress by its dual function as a molecular chaperone to preserve proteostasis and as a cell death antagonist that negatively regulates components of the conserved apoptotic cell death machinery. Deregulated expression of alphaB-crystallin occurs in a broad array of solid tumors and has been linked to tumor progression and poor clinical outcomes. This review will focus on new insights into the molecular mechanisms by which oncogenes, oxidative stress, matrix detachment and other tumor microenvironmental stressors deregulate alphaB-crystallin expression. We will also review accumulating evidence pointing to an essential role for alphaB-crystallin in the multi-step metastatic cascade whereby tumor cells colonize distant organs by circumventing a multitude of barriers to cell migration and survival. Finally, we will evaluate emerging strategies to therapeutically target alphaB-crystallin and/or interacting proteins to selectively activate apoptosis and/or derail the metastatic cascade in an effort to improve outcomes for patients with metastatic disease. PMID- 26820758 TI - Plasma membrane calcium ATPases (PMCAs) as potential targets for the treatment of essential hypertension. AB - The incidence of hypertension, the major modifiable risk factor for cardiovascular disease, is increasing. Thus, there is a pressing need for the development of new and more effective strategies to prevent and treat hypertension. Development of these relies on a continued evolution of our understanding of the mechanisms which control blood pressure (BP). Resistance arteries are important in the regulation of total peripheral resistance and BP; changes in their structure and function are strongly associated with hypertension. Anti-hypertensives which both reduce BP and reverse changes in resistance arterial structure reduce cardiovascular risk more than therapies which reduce BP alone. Hence, identification of novel potential vascular targets which modify BP is important. Hypertension is a multifactorial disorder which may include a genetic component. Genome wide association studies have identified ATP2B1, encoding the calcium pump plasma membrane calcium ATPase 1 (PMCA1), as having a strong association with BP and hypertension. Knockdown or reduced PMCA1 expression in mice has confirmed a physiological role for PMCA1 in BP and resistance arterial regulation. Altered expression or inhibition of PMCA4 has also been shown to modulate these parameters. The mechanisms whereby PMCA1 and 4 can modulate vascular function remain to be fully elucidated but may involve regulation of intracellular calcium homeostasis and/or comprise a structural role. However, clear physiological links between PMCA and BP, coupled with experimental studies directly linking PMCA1 and 4 to changes in BP and arterial function, suggest that they may be important targets for the development of new pharmacological modulators of BP. PMID- 26820759 TI - Viral infections of the central nervous system in elderly patients: a retrospective study. AB - OBJECTIVES: Very few data exist on viral meningitis and encephalitis in elderly patients (>65 years old). METHODS: This study investigated the detection of herpes simplex virus (HSV), varicella zoster virus (VZV), human herpes virus 6 (HHV-6), HHV-7, HHV-8, cytomegalovirus (CMV), Epstein-Barr virus (EBV), enterovirus (EV), human adenovirus (HAdV), human parechoviruses (HPeVs), and tick borne encephalitis virus (TBEV) through real-time PCR (RT-PCR) in patients >65 years old who had cerebrospinal fluid (CSF) tested for a suspected central nervous system infection. RESULTS: A total of 2868 RT-PCRs were performed on 502 CSF samples. Overall, 65 positive RT-PCRs were found: 23 for HSV (35.4% of positives), 15 for EV (23.1% of positives), 14 for EBV (21.5% of positives), 12 for VZV (18.5% of positives), and one for CMV (1.5% of positives). A positive RT PCR in CSF was detected in 24 (17.4%) patients aged >= 80 years and in 35 (9.6%) patients aged 65-79 years (p=0.02). VZV was more frequently detected in the oldest subjects (5.9% vs. 1.6%, p=0.03). CONCLUSIONS: HSV was the most common viral aetiology identified in the study, with VZV infection being recognized more frequently in those patients aged >= 80 years. PMID- 26820760 TI - National survey data for zoonotic schistosomiasis in the Philippines grossly underestimates the true burden of disease within endemic zones: implications for future control. AB - Zoonotic schistosomiasis has a long endemic history in the Philippines. Human mass drug administration has been the cornerstone of schistosomiasis control in the country for the past three decades. Recent publications utilizing retrospective national survey data have indicated that the national human prevalence of the disease is <1%, hence the disease is now close to elimination. However, the evidence for such a claim is weak, given that less than a third of the human population is currently being treated annually within endemic zones and only a third of those treated actually swallow the tablets. For those who consume the drug at the single oral dose of 40mg/kg, the estimated cure rate is 52% based on a recent meta-analysis. Thus, approximately 5% of the endemic human population is in reality receiving the appropriate treatment. To compound this public health problem, most of the bovines in the endemic communities are concurrently infected but are not treated under the current national control programme. Given this evidence, it is believed that the human prevalence of schistosomiasis within endemic regions has been grossly underestimated. Inherent flaws in the reporting of national schistosomiasis prevalence data are reported here, and the problems of utilizing national retrospective data in making geographic information system (GIS) risk maps and advising policy makers of the outcomes are highlighted. PMID- 26820762 TI - Postpartum anxiety and adjustment disorders in parents of infants with very low birth weight: Cross-sectional results from a controlled multicentre cohort study. AB - BACKGROUND: Both preterm delivery and survival rates of very low birth weight (VLBW: <1500 g) infants are increasing. To date, the focus on studies about postpartum mental health after preterm birth has been on depression and on women. There is a paucity of research regarding prevalence, risks, and predictors of postpartum anxiety in parents after VLBW birth. METHODS: Parents with VLBW infants and parents with term infants were recruited into the longitudinal HaFEn study at the three largest centers of perinatal care in Hamburg, Germany. State anxiety was assessed with the State-Trait-Anxiety Inventory and anxiety and adjustment disorders with a clinical interview one month postpartum. Psychiatric lifetime diagnoses, social support, trait anxiety, stress during birth, socioeconomic status, risks during pregnancy, and mode of delivery were also evaluated. To examine predictors of postpartum state anxiety in both parents simultaneously a multiple random coefficient model was used. RESULTS: 230 mothers and 173 fathers were included. The risk for minor/major anxiety symptoms and adjustment disorders was higher in parents with VLBW infants compared to the term group. The risk for anxiety disorders was not higher in parents with VLBW infants. The most important predictors for postpartum state anxiety were high trait anxiety, the birth of a VLBW infant, high stress during birth, and low social support. LIMITATIONS: Data reported here are cross-sectional. Thus, temporal relationships cannot be established. CONCLUSIONS: Our results emphasize the importance of early screening for postpartum anxiety in both parents with VLBW infants. PMID- 26820761 TI - Long-term risk of myocardial infarction and stroke in bipolar I disorder: A population-based Cohort Study. AB - OBJECTIVES: To estimate the risk of fatal and non-fatal myocardial infarction (MI) and stroke in patients with bipolar I disorder compared to people without bipolar I disorder. METHOD: Utilizing a records-linkage system spanning 30 years (1966-1996), a population-based cohort of 334 subjects with bipolar I disorder and 334 age and sex-matched referents from Olmsted County, Minnesota, U.S. was identified. Longitudinal follow-up continued until incident MI or stroke (confirmed by board-certified cardiologist/neurologist), death, or study end date (December 31, 2013). Cox proportional hazards models assessed the hazard ratio (HR) for MI or stroke, adjusting for potential confounders. RESULTS: There was an increased risk of fatal or non-fatal MI or stroke (as a composite outcome) in patients with bipolar I disorder [HR 1.54, 95% confidence interval (CI) 1.02, 2.33; p=0.04]. However, after adjusting for baseline cardiovascular risk factors (alcoholism, hypertension, diabetes, and smoking), the risk was no longer significantly increased (HR 1.19, 95% CI 0.76, 1.86; p=0.46). LIMITATIONS: Small sample size for the study design. Findings were not retained after adjustment for cardiovascular disease risk factors. Psychotropic medication use during the follow-up was not ascertained and was not included in the analyses. CONCLUSION: This study in a geographically defined region in the U.S. demonstrated a significant increased risk of MI or stroke in bipolar I disorder, which was no longer significant after adjustment for cardiovascular risk factors. PMID- 26820763 TI - Intraluminal Duodenal Diverticulum Causing Upper GI Obstruction. PMID- 26820764 TI - Experimental investigation of craze morphology of isotactic polypropylene using computed tomography. AB - In this paper we investigated the morphology of crazes formed during the fracture process of polymeric fibres. Computed tomography technique was applied to reconstruct the image of fibrils-voids structure of crazes. This allowed us to investigate the initial stages of crazes formation during the fracture process of mechanically stretched isotactic polypropylene fibres. The density and morphology of crazes were studied at different regions inside the stretched sample. Accordingly, we are able to visualize the internal structure of the stretched fibres in three dimensions. This revealed in-depth information on the fracture process of polymeric fibres. PMID- 26820765 TI - A high-throughput mass spectrometry assay to simultaneously measure intact insulin and C-peptide. AB - BACKGROUND: Measurements of fasting levels of insulin and C-peptide are useful in documenting insulin resistance and may help predict development of diabetes mellitus. However, the specific insulin and C-peptide levels associated with specific degrees of insulin resistance have not been defined, owing to marked variability among immunoassays and lack of standardization. Herein, we describe a multiplexed liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for intact insulin and C-peptide. METHODS: Insulin and C-peptide were enriched from patient sera using monoclonal antibodies immobilized on magnetic beads and processed on a robotic liquid handler. Eluted peptides were analyzed by LC-MS/MS. Bovine insulin and a stable isotopically-labeled (13C/15N) C-peptide were utilized as internal standards. RESULTS: The assay had an analytical measurement range of 3 to 320 MUIU/ml (18 to 1920 pmol/l) for insulin and 0.11 to 27.2 ng/ml (36 to 9006 pmol/l) for C-peptide. Intra- and inter-day assay variation was less than 11% for both peptides. Of the 5 insulin analogs commonly prescribed to treat diabetes, only the recombinant drug insulin lispro caused significant interference for the determination of endogenous insulin. There were no observed interferences for C-peptide. CONCLUSION: We developed and validated a high throughput, quantitative, multiplexed LC-MS/MS assay for intact insulin and C peptide. PMID- 26820766 TI - Craniometaphyseal dysplasia with obvious biochemical abnormality and rickets-like features. AB - BACKGROUND: Craniometaphyseal dysplasia (CMD) is a rare genetic disorder that is characterized by progressive sclerosis of the craniofacial bones and metaphyseal widening of long bones, and biochemical indexes were mostly normal. To further the understanding of the disease from a biochemical perspective, we reported a CMD case with obviously abnormal biochemical indexes. CASE REPORT: A 1-year-old boy was referred to our clinic. Biochemical test showed obviously increased alkaline phosphatase (ALP) and parathyroid hormone (PTH), mild hypocalcemia and hypophosphatemia. Moreover, significant elevated receptor activator of nuclear factor kappa-B ligand (RANKL) level, but normal beta-C-terminal telopeptide of type I collagen (beta-CTX) concentration were revealed. He was initially suspected of rickets, because the radiological examination also showed broadened epiphysis in his long bones. Supplementation with calcium and calcitriol alleviated biochemical abnormality. However, the patient gradually developed osteosclerosis which was inconformity with rickets. Considering that he was also presented with facial paralysis and nasal obstruction symptom, the diagnosis of craniometaphyseal dysplasia was suspected, and then was confirmed by the mutation analysis of ANKH of the proband and his family, which showed a de novo heterozygous mutation (C1124-1126delCCT) on exon 9. CONCLUSIONS: Our study revealed that obvious biochemical abnormality and rickets-like features might present as uncommon characteristics in CMD patients, and the calcium and calcitriol supplementation could alleviate biochemical abnormalities. Furthermore, although early osteoclast differentiation factor was excited in CMD patient, activity of osteoclast was still inert. PMID- 26820767 TI - Purification and Characterization of Glucose 6-Phosphate Dehydrogenase, 6 Phosphogluconate Dehydrogenase, and Glutathione Reductase from Rat Heart and Inhibition Effects of Furosemide, Digoxin, and Dopamine on the Enzymes Activities. AB - The present study was aimed to investigate characterization and purification of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and glutathione reductase from rat heart and the inhibitory effect of three drugs. The purification of the enzymes was performed using 2',5'-ADP sepharose 4B affinity material. The subunit and the natural molecular weights were analyzed by SDS-PAGE and gel filtration. Biochemical characteristics such as the optimum temperature, pH, stable pH, and salt concentration were examined for each enzyme. Types of product inhibition and Ki values with Km and Vmax values of the substrates and coenzymes were determined. According to the obtained Ki and IC50 values, furosemide, digoxin, and dopamine showed inhibitory effect on the enzyme activities at low millimolar concentrations in vitro conditions. Dopamine inhibited the activity of these enzymes as competitive, whereas furosemide and digoxin inhibited the activity of the enzyme as noncompetitive. PMID- 26820768 TI - Sequencing of FTO and ALKBH5 in men undergoing infertility work-up identifies an infertility-associated variant and two missense mutations. AB - OBJECTIVE: To assess whether men with reduced semen quality exhibit genetic variants in the genes coding for the messenger RNA methylation erasers FTO and ALKBH5. DESIGN: DNA of men undergoing infertility work-up was extracted and the FTO and ALKBH5 genes were sequenced. Statistical analysis was used to study the correlation between the identified ALKBH5 and FTO variants and sperm quality. SETTING: University hospital infertility clinic. PATIENT(S): Semen samples from 77 unselected men that had been referred to Oslo University Hospital for routine semen analysis as part of infertility work-up. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Immunohistochemistry and Western blot were used to confirm the presence of ALKBH5 and FTO in human testis. DNA extraction from samples was followed by Illumina MiSeq amplicon high throughput sequencing and sequence alignment. Variant calling was carried out using GATK's UnifiedGenotyper. Standard semen parameter analysis was performed according to World Health Organization guidelines. RESULT(S): We found an FTO genetic variant to be associated with reduced semen quality. We also identified two FTO missense variants, one mutation (p.Cys326Ser) was located in the important linker between the two protein domains; the other mutation (p.Ser256Asn) was situated in a flexible loop able to interact with other molecules. CONCLUSION(S): The discovery of two missense mutations with potentially detrimental effect on the functionality of the methylation eraser protein FTO, as well as a genetic variant of the same protein that is associated with altered semen quality could suggest that aberrant demethylation of messenger RNA is a factor involved in reduced male fertility. PMID- 26820769 TI - Optimal endometrial preparation for frozen embryo transfer cycles: window of implantation and progesterone support. AB - With significant improvements in cryopreservation technology (vitrification) the number of frozen ET IVF cycles is increasing and may soon surpass in numbers and success rates those of fresh stimulated IVF cycles. Increasing numbers of elective single ETs are also resulting in more frozen embryos (blastocysts) available for subsequent frozen ET cycles. Optimal endometrial preparation and identification of the receptive window for ET in frozen ET cycles thus assumes utmost importance for insuring the best frozen ET outcomes. Reliable data are essential for defining the optimal endometrial preparation protocols with accurate determination of the implantation window in frozen ET cycles. PMID- 26820770 TI - Number of biopsied trophectoderm cells is likely to affect the implantation potential of blastocysts with poor trophectoderm quality. AB - OBJECTIVE: To evaluate whether the developmental potential of the blastocyst is affected by the number of trophectoderm (TE) cells biopsied in preimplantation genetic diagnosis (PGD) cycles. DESIGN: Retrospective study. SETTING: University affiliated center. PATIENT(S): Women underwent PGD cycles of blastocyst biopsy and fluorescence in situ hybridization analysis. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Biopsied TE cell number of blastocysts, survival, and implantation rates. RESULT(S): The biopsied TE cell number was affected by the TE quality and experience of different embryologists. The diagnostic efficiency increased when from one to five cells were biopsied (86.7%, 91.7%%, 96.0%, 96.8%, to 98.7%) and was maximized when more than six cells were biopsied. To compare the clinical efficiencies, blastocysts were divided into four groups according to biopsied TE cell number: 1-5, 6-10, 11-15, and 16-41. For the blastocysts with grade A TE score, no significant difference was observed in the survival and implantation rates among the four groups. For the blastocysts with grades B and C TE scores, the survival rates showed no significant differences among the four groups, but a significant decreasing trend in implantation rates was observed with increasing biopsied TE cell number. CONCLUSION(S): The implantation potential is negatively affected by the biopsied TE cell number in blastocysts with poor TE morphological score. PMID- 26820771 TI - Prospective evaluation of the impact of intermenstrual bleeding on natural fertility. AB - OBJECTIVE: To evaluate the impact of an episode of intermenstrual bleeding on the probability of conception in a menstrual cycle (fecundability). DESIGN: Prospective, time-to-pregnancy cohort study. SETTING: Community-based cohort. PATIENT(S): Women trying to conceive, ages 30 to 44 years, without known infertility. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Current cycle and subsequent cycle fecundability. RESULT(S): A total of 549 women provided 1,552 complete cycles for analysis. Intermenstrual and luteal bleeding were reported in 36% and 34% of cycles, respectively. Ninety-three percent of all intermenstrual bleeding was luteal. Cycles in which women had intermenstrual bleeding or luteal bleeding were statistically significantly less likely to result in conception (fecundability ratio [FR] 0.23; 95% confidence interval [CI], 0.16-0.34; and FR 0.22; 95% CI, 0.14-0.33). Women with an episode of intermenstrual and luteal bleeding had a statistically significant increase in the probability of pregnancy in the subsequent cycle (FR 1.61; 95% CI, 1.15-2.25; and FR 2.01; 95% CI, 1.52-2.87, respectively). CONCLUSION(S): Intermenstrual bleeding statistically significantly decreases the odds of conceiving in that cycle but does not appear to negatively impact a woman's immediate future reproductive potential. CLINICAL TRIAL REGISTRATION NUMBER: NCT01028365. PMID- 26820772 TI - Subchorionic hematomas are increased in early pregnancy in women taking low-dose aspirin. AB - OBJECTIVE: To determine the frequency of subchorionic hematomas (SCH) in first trimester ultrasound examinations of patients with infertility and recurrent pregnancy loss (RPL) and in patients from a general obstetric population. To determine if the method of assisted reproduction utilized or the use of anticoagulants, such as heparin and aspirin (ASA), influenced frequency of SCH. DESIGN: Prospective, cohort study. SETTING: Fertility clinic and general obstetrics clinic. PATIENT(S): Five hundred and thirty-three women who were pregnant in the first-trimester. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Frequencies of subchorionic hematomas in women based on diagnosis, use of anticoagulants, and fertility treatment. RESULT(S): SCH were identified in 129/321 (40.2%) in the study group compared to 23/212 (10.9%) in the control group. Fertility diagnosis and the use of heparin did not appear to affect the frequency of SCH in the first trimester; however, SCH occurred at an almost four fold increase in patients taking ASA compared to those not taking ASA, regardless of fertility diagnosis or method of fertility treatment. CONCLUSION(S): The use of ASA may be associated with an increased risk of developing a SCH during the first trimester. The increased frequencies of SCH in pregnancies of patients attending a fertility clinic compared to women from a general obstetrical practice was highly correlated with the use of ASA. PMID- 26820773 TI - Correction to "Oxalates as Activating Groups for Alcohols in Visible Light Photoredox Catalysis: Formation of Quaternary Centers by Redox-Neutral Fragment Coupling". PMID- 26820774 TI - Oral intake of genetically engineered high-carotenoid corn ameliorates hepatomegaly and hepatic steatosis in PTEN haploinsufficient mice. AB - Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease. Here we show that a mouse model of haploinsufficiency in the lipid and protein phosphatase and tensin homolog protein (PTEN(+/-)) exhibits hepatomegaly, increased liver lipogenic gene expression (SREBP-1C and PPARgamma) and hepatic lesions analogous to human NAFLD. The livers of PTEN(+/-) mice also contained lower levels of retinoic acid (RA) than normal, similarly to human NAFLD patients. The RA signaling pathway thus offers a novel therapeutic target for the treatment of NAFLD although the impact of nutrition in this context is unclear. We therefore fed PTEN(+/-) mice for 36weeks a diet containing genetically engineered high-carotenoid corn (HCAR) to investigate its potential beneficial effects on the hepatic symptoms of NAFLD. The HCAR diet reduced hepatomegaly and promoted the repartitioning of fatty acids in the liver, away from triacylglycerol storage. At the molecular level, the HCAR diet clearly reduced lipogenic gene expression, boosted catabolism, and increased hepatic RA levels. These results set the stage for human trials to evaluate the use of high carotenoid foods for the reduction or prevention of steatosis in NAFLD. PMID- 26820775 TI - Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate. AB - Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications. PMID- 26820776 TI - Encouraging children to eat more fruit and vegetables: Health vs. descriptive social norm-based messages. AB - Traditional intervention approaches to promote fruit and vegetable consumption outline the health benefits of eating fruit and vegetables. More recently, social norm-based messages describing the healthy eating habits of others have been shown to increase fruit and vegetable intake in adults. Here we report two experimental studies which investigated whether exposure to descriptive social norm-based messages about the behaviour of other children and health-based messages increased fruit and vegetable intake in young children. In both studies children were exposed to messages whilst playing a board-game. After exposure to the messages, children were able to consume fruit and vegetables, as well as high calorie snack foods. Although findings were inconsistent across the two individual studies, in a pooled analysis we found evidence that both health messages and descriptive social norm-based messages increased children's fruit and vegetable intake, relative to control condition messages (p < .05). Whether descriptive social norm-based messages can be used to promote meaningful changes to children's dietary behaviour warrants further study. PMID- 26820777 TI - Engineered/designer biochar for contaminant removal/immobilization from soil and water: Potential and implication of biochar modification. AB - The use of biochar has been suggested as a means of remediating contaminated soil and water. The practical applications of conventional biochar for contaminant immobilization and removal however need further improvements. Hence, recent attention has focused on modification of biochar with novel structures and surface properties in order to improve its remediation efficacy and environmental benefits. Engineered/designer biochars are commonly used terms to indicate application-oriented, outcome-based biochar modification or synthesis. In recent years, biochar modifications involving various methods such as, acid treatment, base treatment, amination, surfactant modification, impregnation of mineral sorbents, steam activation and magnetic modification have been widely studied. This review summarizes and evaluates biochar modification methods, corresponding mechanisms, and their benefits for contaminant management in soil and water. Applicability and performance of modification methods depend on the type of contaminants (i.e., inorganic/organic, anionic/cationic, hydrophilic/hydrophobic, polar/non-polar), environmental conditions, remediation goals, and land use purpose. In general, modification to produce engineered/designer biochar is likely to enhance the sorption capacity of biochar and its potential applications for environmental remediation. PMID- 26820778 TI - Pre-adaptive cadmium tolerance in the black garden ant. AB - The black garden ant Lasius niger is a common component of habitats subjected to anthropological stress. The species can develop very abundant populations in metal-polluted areas. In this study, we raised the question of its tolerance to Cd pollution. Workers of L. niger were collected from 54 colonies, originating from 19 sites located along an increasing gradient of Cd pollution in Poland. Ants were exposed to a range of dietary Cd concentrations in a controlled 14-day laboratory experiment in order to test Cd-sensitivity in the investigated ants. The level of ant mortality was recorded as the endpoint of the experiment. We used much higher concentrations of dietary Cd than those the ants are most likely exposed to in field conditions. The investigated ants were highly Cd-tolerant; even a very high dietary Cd concentration of approx. 1300 mg/kg did not affect mortality of workers when compared to the control. Mortality was unrelated to Cd pollution along the pollution gradient, meaning that high Cd-tolerance can be found even in ants from unpolluted areas. The results stress the importance of pre-adaptive mechanisms in the development of metal tolerance in ants. PMID- 26820779 TI - Experimental and computational study of membrane affinity for selected energetic compounds. AB - The affinity of various energetic compounds for a biological membrane was investigated using experimental and computational techniques. We measured octanol water (log(Kow)) and liposome-water (log(Klipw)) partition coefficients for the following chemicals: trinitrotoluene (TNT), 2,4-dinitrotoluene (2,4-DNT), 2,6 dinitrotoluene (2,6-DNT), 2,4-dinitroanisole (DNAN), 2methoxy-5-nitrophenol (2M5NP), 2,4,6-trinitrobenzene (TNB), and 2,4-dinitrophenol (2,4-DNP). In order to determine log(Klipw) experimentally, we used artificial solid supported lipid liposomes produced under trade mark TRANSIL. Log(Kow) value were predicted with several program packages including the COSMOthermX software. Log(Klipw) were estimated with COSMOmic as implemented in the COSMOthermX program package. In order to verify accuracy of our experimentally obtained results, we performed basic statistical analysis of data taken from the literature. We concluded that compounds considered in this study possess a moderate ability to penetrate into membranes. Comparison of both coefficients has shown that in general, the log(Kow) values are slightly smaller than log(Klipw). PMID- 26820780 TI - Bioconcentration of ionic cadmium and cadmium selenide quantum dots in zebrafish larvae. AB - The concern related to the use of nanomaterials is growing nowadays, especially the risk associated with their emission or exposure. One type of nanomaterials that has attracted much attention is quantum dots (QDs). QDs incorporation in consumer goods increases the probability of their entering in the environment and then into living organisms and human. In order to evaluate their potential to be bioconcentrated, zebrafish larvae have been exposed to SeCd/ZnS QDs, after performing an exhaustive characterization of these nanoparticles under the assay conditions. These data were compared with those obtained when zebrafish larvae were exposed to ionic cadmium. Finally, distribution of ionic Cd and QDs in exposed zebrafish larvae have been evaluated by Laser Ablation ICP-MS. PMID- 26820781 TI - Polycyclic aromatic hydrocarbons (PAHs) removal by sorption: A review. AB - Polycyclic aromatic hydrocarbons (PAHs) are organic micro pollutants which are persistent compounds in the environment due to their hydrophobic nature. Concerns over their adverse effects in human health and environment have resulted in extensive studies on various types of PAHs removal methods. Sorption is one of the widely used methods as PAHs possess a great sorptive ability into the solid media and their low aqueous solubility property. Several adsorbent media such as activated carbon, biochar, modified clay minerals have been largely used to remove PAHs from aqueous solution and to immobilise PAHs in the contaminated soils. According to the past studies, very high removal efficiency could be achieved using the adsorbents such as removal efficiency of activated carbon, biochar and modified clay mineral were 100%, 98.6% and >99%, respectively. PAHs removal efficiency or adsorption/absorption capacity largely depends on several parameters such as particle size of the adsorbent, pH, temperature, solubility, salinity including the production process of adsorbents. Although many studies have been carried out to remove PAHs using the sorption process, the findings have not been consolidated which potentially hinder to get the correct information for future study and to design the sorption method to remove PAHs. Therefore, this paper summarized the adsorbent media which have been used to remove PAHs especially from aqueous solutions including the factor affecting the sorption process reported in 142 literature published between 1934 and 2015. PMID- 26820782 TI - Biotransformation of OH-PBDEs by pig liver microsomes: Investigating kinetics, identifying metabolites, and examining the role of different CYP isoforms. AB - Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are of great concern due to their potential risk to animal and human health. The biotransformation potential of OH-PBDEs in organisms is important for the understanding of their health risk. In the present study, the biotransformation of 3'-OH-2,4-di-BDE (3' OH-BDE-7), 4'-OH-2,2',4-tri-BDE (4'-OH-BDE-17) and 3-OH-2,2',4,4'-tetra-BDE (3-OH BDE-47) by pig liver microsomes was studied. Compared with their precursor PBDEs, the three OH-PBDEs were more readily biotransformed by pig liver microsomes, and the biotransformation rate followed the order: 3'-OH-BDE-7 > 4'-OH-BDE-17 > 3-OH BDE-47. These results revealed that the biotransformation rate of OH-PBDEs was decreased with an increase in the number of bromine substituents. Cleavage of the diphenyl ether bond was the dominant pathway for biotransformation of the three OH-PBDEs by pig liver microsomes, while debromination and hydroxylation were found to be of less importance. CYP3A4 was suggested to be the specific enzyme responsible for the biotransformation of OH-PBDEs via associated inhibition assay. These findings may enrich our understanding of health risk associated with OH-PBDEs in mammals and human beings. PMID- 26820783 TI - The modified tower vertical filler technique for the treatment of post-acne scarring. AB - BACKGROUND: Acne scarring remains a difficult problem for patients and physicians. Often it is treated as a two-dimensional disease with lasers and similar devices, whereas it is really a three-dimensional problem. Fillers have been used for many years but recently fillers with more lifting potential have been made available and serve the purpose of the selective elevation of atrophic scars, adding the third dimension to treatment. METHODS: Five patients with atrophic acne scarring were selected in this pilot study. Each patient was treated twice with a 3-month follow up from the second treatment. A vertical modified tower technique was used with a hyaluronic acid filler to lift each scar and support the skin to adopt a more flattened appearance. RESULTS: The mean scar count declined from 48.8 scars to 15.4 visible after the second session. The mean volume to total correction with filler of all scars declined from 1.144 mL to 0.525 mL from the first to second session. Global subjective improvement was assessed at 5.4 and 5.5 (-3 to +10 scale). The static objective grading scale showed an improvement from 3.2 at time of first treatment to 3.0 at the second, to 2.6 at final review. CONCLUSIONS: The relative speed, accuracy and efficacy of high lift hyaluronic acid is shown in this small case series with subjective and objective measurement. PMID- 26820784 TI - Periorbital Allergic Contact Dermatitis Caused by Lanolin in a Lubricating Eye Ointment. PMID- 26820785 TI - Adopting the orphan: The importance of recognising hidradenitis suppurativa as a systemic auto-inflammatory disease. PMID- 26820786 TI - Extrafacial lentigo maligna melanoma is reported often in Australia, more so at lower latitudes. PMID- 26820787 TI - Verrucous melanoma simulating melanoacanthoma: Dermoscopic, reflectance confocal microscopic and high-definition optical coherence tomography presentation of a rare melanoma variant. PMID- 26820788 TI - Immunoglobulin Type Gamma 4-Related Disease Presenting with Cutaneous Plaques. PMID- 26820789 TI - Multiple familial pilomatrixomas in the absence of other clinical features: a case of familial benign pilomatrixoma. PMID- 26820790 TI - Congenital self-healing reticulohistiocytosis: the need for investigation. PMID- 26820791 TI - Seek and You shall Find. PMID- 26820792 TI - Fisetin, heme oxigenase-1 (HO-1) and M2-macrophages in keratinocyte response to stress. PMID- 26820793 TI - Genome-wide quantification of 5'-phosphorylated mRNA degradation intermediates for analysis of ribosome dynamics. AB - Co-translational mRNA degradation is a widespread process in which 5'-3' exonucleolytic degradation follows the last translating ribosome, thus producing an in vivo ribosomal footprint that delimits the 5' position of the mRNA molecule within the ribosome. To study this degradation process and ribosome dynamics, we developed 5PSeq, which is a method that profiles the genome-wide abundance of mRNA degradation intermediates by virtue of their 5'-phosphorylated (5'P) ends. The approach involves targeted ligation of an oligonucleotide to the 5'P end of mRNA degradation intermediates, followed by depletion of rRNA molecules, reverse transcription of 5'P mRNAs and Illumina high-throughput sequencing. 5PSeq can identify translational pauses at rare codons that are often masked when using alternative methods. This approach can be applied to previously extracted RNA samples, and it is straightforward and does not require polyribosome purification or in vitro RNA footprinting. The protocol we describe here can be applied to Saccharomyces cerevisiae and potentially to other eukaryotic organisms. Three days are required to generate 5PSeq libraries. PMID- 26820794 TI - High-sensitivity infrared attenuated total reflectance sensors for in situ multicomponent detection of volatile organic compounds in water. AB - In situ detection of volatile organic compounds (VOCs) in aqueous environments is imperative for ensuring the quality and safety of water supplies, yet it remains a challenging analytical task. We present a high-sensitivity method for in situ analysis of multicomponent VOCs at low concentrations based on the use of infrared attenuated total reflection (IR-ATR) spectroscopy. This protocol uses a unique ATR waveguide, which comprises a planar silver halide (AgCl(x)Br(1-x)) fiber with cylindrical extensions at both ends to increase the number of internal reflections, and a polymer coating that traps VOCs and excludes water molecules. Depending on the type of VOC and measurement scenario, IR spectra with specific frequency windows, scan times and spectral resolutions are obtained, from which concentration information is derived. This protocol allows simultaneous detection of multiple VOCs at concentrations around 10 p.p.b., and it enables accurate quantification via a single measurement within 5 min without the need for sample collection or sample pretreatment. This IR-ATR sensor technology will be useful for other applications; we have included a procedure for the analysis of protein conformation changes in Supplementary Methods as an example. PMID- 26820795 TI - In vitro assay to determine SUMOylation sites on protein substrates. AB - Protein SUMOylation regulates the activity of a wide range of cellular substrates, and the identification of small ubiquitin-related modifier (SUMO) modified sites is often required to understand how this modification affects protein function. However, the site-specific identification of modified lysine residues by mass spectrometry (MS) remains challenging because of the dynamic nature of this modification, its low stoichiometry and the relatively large SUMO remnant left on peptide backbones after tryptic digestion. Here we report a versatile method to identify sites and to profile the extent of modification on recombinant proteins from in vitro SUMOylation assays. We define the steps required for sample preparation, and we describe how to perform proper controls and conduct the liquid chromatography-MS (LC-MS) and bioinformatics analyses. Native protein substrates can be used for the assay, although we recommend the use of His-tagged proteins to facilitate removal of contaminants. The procedure was developed for human SUMO paralogs, and it requires <2 d for completion. PMID- 26820796 TI - Spectral Features and Charge Dynamics of Lead Halide Perovskites: Origins and Interpretations. AB - Lead halide perovskite solar cells are presently the forerunner among the third generation solution-processed photovoltaic technologies. With efficiencies exceeding 20% and low production costs, they are prime candidates for commercialization. Critical insights into their light harvesting, charge transport, and loss mechanisms have been gained through time-resolved optical probes such as femtosecond transient absorption spectroscopy (fs-TAS), transient photoluminescence spectroscopy, and time-resolved terahertz spectroscopy. Specifically, the discoveries of long balanced electron-hole diffusion lengths and gain properties in halide perovskites underpin their significant roles in uncovering structure-function relations and providing essential feedback for materials development and device optimization. In particular, fs-TAS is becoming increasingly popular in perovskite characterization studies, with commercial one box pump-probe systems readily available as part of a researcher's toolkit. Although TAS is a powerful probe in the study of charge dynamics and recombination mechanisms, its instrumentation and data interpretation can be daunting even for experienced researchers. This issue is exacerbated by the sensitive nature of halide perovskites where the kinetics are especially susceptible to pump fluence, sample preparation and handling and even degradation effects that could lead to disparate conclusions. Nonetheless, with end-users having a clear understanding of TAS's capabilities, subtleties, and limitations, cutting-edge work with deep insights can still be performed using commercial setups as has been the trend for ubiquitous spectroscopy instruments like absorption, fluorescence, and transient photoluminescence spectrometers. Herein, we will first briefly examine the photophysical processes in lead halide perovskites, highlighting their novel properties. Next, we proceed to give a succinct overview of the fundamentals of pump-probe spectroscopy in relation to the spectral features of halide perovskites and their origins. In the process, we emphasize some key findings of seminal photophysical studies and draw attention to the interpretations that remain divergent and the open questions. This is followed by a general description into how we prepare and conduct the TAS characterization of CH3NH3PbI3 thin films in our laboratory with specific discussions into the potential pitfalls and the influence of thin film processing on the kinetics. Lastly, we conclude with our views on the challenges and opportunities from the photophysical perspective for the field and our expectations for systems beyond lead halide perovskites. PMID- 26820797 TI - Pre-clinical use of isogenic cell lines and tumours in vitro and in vivo for predictive biomarker discovery; impact of KRAS and PI3KCA mutation status on MEK inhibitor activity is model dependent. AB - Studies to identify predictive biomarkers can be carried out in isogenic cancer cell lines, which enable interrogation of the effect of a specific mutation. We assessed the effects of four drugs, the PI3K-mammalian target of rapamycin inhibitor dactolisib, the PI3K inhibitor pictrelisib, and the MEK (MAPK/ERK Kinase) inhibitors PD 0325901 and selumetinib, in isogenic DLD1 parental, KRAS(+/ ), KRAS(G13D/-), PIK3CA(+/-) and PIK3CA(E545K/-) colorectal carcinoma cell lines. Importantly, we found substantial differences in the growth of these cells and in their drug sensitivity depending on whether they were studied under 2D (standard tissue culture on plastic) or 3D (in vitro soft agar and in vivo xenograft) conditions. DLD1 KRAS(+/-) and DLD1 PIK3CA(+/-) cells were more sensitive to MEK inhibitors than parental, DLD1 KRAS(G13D/-) and DLD1 PIK3CA(E545K/-) cells under 2D conditions, whereas DLD1 KRAS(G13D/-) and DLD1 PIK3CA(E545K/-) xenografts were sensitive to 10 mg/kg daily *14 PD 0325901 in vivo (p <= 0.02) but tumours derived from parental DLD1 cells were not. These findings indicate that KRAS and PIK3CA mutations can influence the response of DLD1 colorectal cancer cell lines to MEK and PI3K inhibitors, but that the effect is dependent on the experimental model used to assess drug sensitivity. PMID- 26820798 TI - Models Predictive of Metabolic Syndrome Components in Obese Pediatric Patients. AB - BACKGROUND AND AIMS: Components of metabolic syndrome (MetS) are complications caused by abdominal obesity and insulin resistance (IR). Diagnosis of MetS by clinical indicators could help to identify patients at risk of cardiovascular disease and type 2 diabetes. We undertook this study to propose predictive indicators of MetS in obese children and adolescents. METHODS: A cross-sectional study was carried out. After obtaining informed consent and the registration of the study with an institutional research committee, 172 obese patients from an Obesity Clinic, aged 6-15 years, were included. Variables included were waist circumference (WC), glucose, high-density lipoprotein (HDL), triglycerides (TGL), blood pressure, insulin resistance (by homeostatic model assessment HOMA-index), acanthosis nigricans (AN), uric acid, serum glutamic oxaloacetic transaminase (GOT) and alanine transaminase, and hepatic sonogram. International standards for age and sex variables were used. Multivariate analysis was applied. RESULTS: Variables predicted components of MetS in children: HOMA-IR (insulin resistance by HOMA index) was increased by 2.4 in hepatic steatosis, by 0.6 for each unit of SUA (serum uric acid), and by 0.009 for every mg/dL of triglycerides. In adolescents, every cm of waist circumference increased systolic blood pressure by 0.6 mmHg, and each unit of SUA increased it by 2.9 mmHg. CONCLUSIONS: Serum uric acid and waist circumference are useful and accessible variables that can predict an increased risk of cardiovascular disease in obese pediatric patients. PMID- 26820799 TI - Postprandial Changes in Chemokines Related to Early Atherosclerotic Processes in Familial Hypercholesterolemic Subjects: A Preliminary Study. AB - BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is associated with higher levels of inflammatory mediators such as chemokines, which contribute to an increased risk of premature atherosclerosis in these patients. We studied the response of chemokines related to early atherosclerotic processes during an oral unsaturated fat load test (OFLT) in patients with heterozygous FH and compared this response to normolipidemic and normoglycemic subjects. METHODS: Blood samples were taken from 12 FH patients and 20 healthy controls with a similar age, gender distribution, and body mass index. Plasma chemokine levels were determined in both groups in a fasting state and at 2, 4, 6, and 8 h after an OFLT using human cytokine multiplex kits (Linco) and a Luminex LABScanTM100 system. RESULTS: In the fasting state MIP-1beta, MIP-1alpha, IP-10, IFN-gamma, MCP-1, and IL-8 were significantly increased in the FH group compared to the healthy controls (p <0.05). In addition, a significant decrease in postprandial chemokine plasma values were found in the FH group compared to fasting values after the OFLT. In normolipidemic nondiabetic controls no significant changes were found in the postprandial state. CONCLUSIONS: There was a postprandial decrease in chemokines related to early atherosclerotic processes after an OFLT in FH patients. These results confirm the influence of dietary patterns in this group of patients. PMID- 26820801 TI - Serum CETP concentration is not associated with measures of body fat: The NEO study. AB - INTRODUCTION: Adipose tissue has been postulated to contribute substantially to the serum cholesteryl ester transfer protein (CETP) pool. However, in a recent large cohort study waist circumference was not associated with plasma CETP. The aim of the present study was to further examine associations of accurate measures of body fat and body fat distribution with serum CETP concentration. METHODS: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, we examined in 6606 participants (aged 45-65 years) the associations of total body fat, body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), abdominal subcutaneous (aSAT) and visceral adipose tissue (VAT) assessed with magnetic resonance imaging (n = 2547) and total and trunk fat mass assessed with dual-energy X-ray absorptiometry (n = 909) with serum CETP concentration. Regression models were adjusted for age, ethnicity, sex, dietary intake of fat and cholesterol, physical activity, smoking and menopausal status. RESULTS: Mean (SD) age was 56 (6) years and BMI 26.3 (4.4) kg/m(2), 56% were women. Mean serum CETP concentration was 2.47 MUg/mL. The difference in serum CETP was 0.02 MUg/mL (95%CI: -0.01, 0.05) per SD total body fat (8.7%), and 0.02 MUg/mL (0.00, 0.04) per SD BMI (4.4 kg/m(2)). Similar associations around the null were observed for waist circumference, WHR, aSAT, VAT, total and trunk fat mass. CONCLUSION: In this population-based study, there was no evidence for clinically relevant associations between several measures of body fat and serum CETP concentration. This finding implies that adipose tissue does not contribute to the CETP pool in serum. PMID- 26820800 TI - Kynurenine pathway metabolites and suicidality. AB - Suicide is a major global problem, claiming more than 800,000 lives annually. The neurobiological changes that underlie suicidal ideation and behavior are not fully understood. Suicidal patients have been shown to display elevated levels of inflammation both in the central nervous system and the peripheral blood. A growing body of evidence suggests that inflammation is associated with a dysregulation of the kynurenine pathway in suicidal patients, resulting in an imbalance of neuroactive metabolites. Specifically, an increase in the levels of the NMDA receptor agonist quinolinic acid and a simultaneous decrease in neuroprotective metabolites have been observed in suicidal patients, and may contribute to the development of suicidality via changes in glutamate neurotransmission and neuroinflammation. The cause of the dysregulation of kynurenine metabolites in suicidality is not known, but is likely due to differential activity of the involved enzymes in patients. As knowledge in these areas is rapidly growing, targeting the kynurenine pathway enzymes may provide novel therapeutic approaches for managing suicidal behavior. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'. PMID- 26820802 TI - A multi-locus genetic risk score for abdominal aortic aneurysm. AB - BACKGROUND: We investigated whether a multi-locus genetic risk scores (GRS) was associated with presence and progression of abdominal aortic aneurysm (AAA) in a case - control study. METHODS AND RESULTS: The study comprised of 1124 patients with AAA (74 +/- 8 years, 83% men, 52% of them with a maximal AAA size <= 5 cm) and 6524 non-cases (67 +/- 11 years, 58% men) from the Mayo Vascular Disease Biorepository. AAA was defined as infrarenal abdominal aorta diameter >= 3.0 cm or history of AAA repair. Non-cases were participants without known AAA. A GRS was calculated using 4 SNPs associated with AAA at genome-wide significance (P <= 10(-8)). The GRS was associated with the presence of AAA after adjustment for age, sex, cardiovascular risk factors, atherosclerotic cardiovascular diseases and family history of aortic aneurysm: odds ratio (OR, 95% confidence interval, CI) 1.06 (1.04-1.09, p < 0.001). Adding GRS to conventional risk factors improved the association of presence of AAA (net reclassification index 14%, p < 0.001). In a subset of patients with AAA who had >= 2 imaging studies (n = 651, mean (SE) growth rate 2.47 (0.11) mm/year during a mean time interval of 5.41 years), GRS, baseline size, diabetes and family history were each associated with aneurysm growth rate in univariate association (all p < 0.05). The estimated mean aneurysm growth rate was 0.50 mm/year higher in those with GRS > median (5.78) than those with GRS <= median (p = 0.01), after adjustment for baseline size (p < 0.001), diabetes (p = 0.046) and family history of aortic aneurysm (p = 0.02). CONCLUSIONS: A multi-locus GRS was associated with presence of AAA and greater aneurysm expansion. PMID- 26820803 TI - Multiple microRNA regulation of lipoprotein lipase gene abolished by 3'UTR polymorphisms in a triglyceride-lowering haplotype harboring p.Ser474Ter. AB - BACKGROUND: Lipoprotein lipase (LPL) is a key enzyme in triglyceride (TG) metabolism. LPL gene single nucleotide polymorphisms (SNPs) are associated with TG concentrations however the functionality of many of these SNPs remains poorly understood. MicroRNAs (miR) exert post-transcriptional down-regulation and their target sequence on the 3'UTR may be altered by SNPs. We therefore investigated whether LPL 3'UTR SNPs could modulate plasma TG concentration through the alteration of miR binding-sites. METHODS AND RESULTS: We performed genetic association studies of LPL 3'UTR SNPs with TG concentrations in 271 type 2 diabetic patients and in general population samples (2997 individuals). A specific LPL haplotype (Hap4) was associated with lower plasma TG concentration (TG-0.18, IC95% [-0.30, -0.07] mmol/L or logTG-0.13, IC95% [-0.18, -0.08], p = 4.77.10(-8)) in the meta-analysis. Hap4 comprises seven 3'UTR SNP minor alleles and p.Ser474Ter (rs328) a well-documented nonsense mutation associated with low TG concentration although by an unknown mechanism so far. Bio-informatic studies identified several putative miRNA binding-sites on the wild-type Hap1 haplotype, lost on Hap4. Functional validation performed in HEK-293T cells using luciferase expression constructs with various LPL 3'UTR allele combinations demonstrated a binding of miR-29, miR-1277 and miR-410 on Hap1, lost on Hap4. This loss of specific miR binding-site in presence of Hap4 was independent of the allelic variation of p.Ser474Ter (rs328). CONCLUSIONS: We report the regulation of LPL by the miR-29, miR-1277 and miR-410 that is lost in presence of Hap4, a specific LPL TG-lowering haplotype. Consequently p.Ser474Ter association with TG concentration could be at least partially explained by its strong linkage disequilibrium with these functional 3'UTR SNPs. PMID- 26820805 TI - Evaluation of an autochthonous starter culture on the production of a traditional dry fermented sausage from Chaco (Argentina) at a small-scale facility. AB - The performance of a mixed starter culture, SAS-1, comprised of the autochthonous strains Lactobacillus sakei ACU-2 and Staphylococcus vitulinus ACU-10, was evaluated into the production process of a traditional dry sausage. Microbiological, physicochemical and sensory analyses were carried out to accomplish this goal. Results showed an improvement in performance through the introduction of SAS-1; adding mixed starter culture rapidly decreased pH, inhibited the growth of contaminant microorganisms and enhanced the beneficial ones, diminished TBARS, and highlighted color and aroma attributes. However, most influential organoleptic descriptors among consumer acceptance were not affected by the addition of the starter. This starter culture would represent a valuable tool to improve the homogeneity of artisanal manufacture of this traditional food. PMID- 26820804 TI - Genetic loci for serum lipid fractions and intracerebral hemorrhage. AB - BACKGROUND: Serum total cholesterol and its fractions are inversely associated with intracerebral hemorrhages (ICH) and their potential subclinical precursor, cerebral microbleeds. To ascertain whether there is a genetic basis for this inverse association, we studied established genetic loci for serum total, LDL, and HDL cholesterol, and triglycerides in their association with ICH and microbleeds. METHODS: Data on 161 genetic variants for serum lipids was collected in 9011 stroke-free participants (mean age 65.8, SD 10.2; 57.9% women) of the population-based Rotterdam Study. Participants were followed from baseline (1997 2005) up to 2013 for the occurrence of ICH. A subset of 4179 participants underwent brain MRI for microbleed assessment between 2005 and 2011. We computed genetic risk scores (GRS) for the joint effect of lipid variants. Cox proportional hazards and logistic regression models were used to investigate the association of GRS of lipid fractions with ICH and microbleeds. RESULTS: After a mean follow-up of 8.7 (SD 4.1) years, 67 (0.7%) participants suffered an ICH. Microbleed prevalence was 19.6%. Higher genetic load for high serum total and LDL cholesterol was associated with an increased risk of ICH. Higher genetic load for high serum LDL cholesterol was borderline associated with a higher prevalence of multiple lobar microbleeds. CONCLUSIONS: Genetic susceptibility for high serum total and LDL cholesterol is positively associated with incident ICH and borderline associated with multiple lobar microbleeds. We did not find a genetic basis for the previously reported inverse association between serum lipid levels and ICH. PMID- 26820807 TI - Controlled Electrochemical Deformation of Liquid-Phase Gallium. AB - Pure gallium is a soft metal with a low temperature melting point of 29.8 degrees C. This low melting temperature can potentially be employed for creating optical components with changeable configurations on demand by manipulating gallium in its liquid state. Gallium is a smooth and highly reflective metal that can be readily maneuvered using electric fields. These features allow gallium to be used as a reconfigurable optical reflector. This work demonstrates the use of gallium for creating reconfigurable optical reflectors manipulated through the use of electric fields when gallium is in a liquid state. The use of gallium allows the formed structures to be frozen and preserved as long as the temperature of the metal remains below its melting temperature. The lens can be readily reshaped by raising the temperature above the melting point and reapplying an electric field to produce a different curvature of the gallium reflector. PMID- 26820806 TI - Sinomenine attenuates airway inflammation and remodeling in a mouse model of asthma. AB - Asthma is an inflammatory disease that involves airway inflammation and remodeling. Sinomenine (SIN) has been demonstrated to have immunosuppressive and anti-inflammatory properties. The aim of the present study was to investigate the inhibitory effects of SIN on airway inflammation and remodeling in an asthma mouse model and observe the effects of SIN on the transforming growth factor beta1 (TGF-beta1)/connective tissue growth factor (CTGF) pathway and oxidative stress. Female BALB/c mice were sensitized by repetitive ovalbumin (OVA) challenge for 6 weeks in order to develop a mouse model of asthma. OVA-sensitized animals received SIN (25, 50 and 75 mg/kg) or dexamethasone (2 mg/kg). A blank control group received saline only. The area of smooth muscle and collagen, levels of mucus secretion and inflammatory cell infiltration were evaluated 24 h subsequent to the final OVA challenge. mRNA and protein levels of TGF-beta1 and CTGF were determined by reverse transcription-quantitative polymerase chain reaction and immunohistology, respectively. The indicators of oxidative stress were detected by spectrophotometry. SIN significantly reduced allergen-induced increases in smooth muscle thickness, mucous gland hypertrophy, goblet cell hyperplasia, collagen deposition and eosinophilic inflammation. The levels of TGF beta1 and CTGF mRNA and protein were significantly reduced in the lungs of mice treated with SIN. Additionally, the total antioxidant capacity was increased in lungs following treatment with SIN. The malondialdehyde content and myeloperoxidase activities in the lungs from OVA-sensitized mice were significantly inhibited by SIN. In conclusion, SIN may inhibit airway inflammation and remodeling in asthma mouse models, and may have therapeutic efficacy in the treatment of asthma. PMID- 26820808 TI - The 10% solution: Tying managerial salary increases to workplace wellness actions (and not results). AB - Although manager support is critical for workplace health and wellness efforts, little is known about how to best encourage managers to make creative or bold steps toward employee wellness. We posit that the right interactions between managers and employees could have lasting impact on workplace wellness. To consider how managers might be motivated to take an active role in promoting everyday employee health and wellness, we used a website survey of worksite managers (N = 270) to investigate how tying at least 10% of managerial annual salary increases and promotion would incentivize manager actions in workplace wellness. Overall, regression analyses reveal favorable attitudes from managers and high intentions to implement changes if salary increases and advancement were partially linked to workplace wellness efforts. Managers also expressed a preference for working for a company with this policy, and this was strongest among female managers and managers with a fewer number of subordinates. (PsycINFO Database Record PMID- 26820809 TI - Solution-Processed Copper/Reduced-Graphene-Oxide Core/Shell Nanowire Transparent Conductors. AB - Copper nanowire (Cu NW) based transparent conductors are promising candidates to replace ITO (indium-tin-oxide) owing to the high electrical conductivity and low cost of copper. However, the relatively low performance and poor stability of Cu NWs under ambient conditions limit the practical application of these devices. Here, we report a solution-based approach to wrap graphene oxide (GO) nanosheets on the surface of ultrathin copper nanowires. By mild thermal annealing, GO can be reduced and high quality Cu r-GO core-shell NWs can be obtained. High performance transparent conducting films were fabricated with these ultrathin core-shell nanowires and excellent optical and electric performance was achieved. The core-shell NW structure enables the production of highly stable conducting films (over 200 days stored in air), which have comparable performance to ITO and silver NW thin films (sheet resistance ~28 Omega/sq, haze ~2% at transmittance of ~90%). PMID- 26820810 TI - Co-expression of FOXL1 and PP2A inhibits proliferation inducing apoptosis in pancreatic cancer cells via promoting TRAIL and reducing phosphorylated MYC. AB - Pancreatic cancer is usually diagnosed in the advanced stages and is sensitive to only few therapies. The forkhead box L1 (FOXL1) and protein phosphatase 2A (PP2A) have been recognized to be tumor suppressive in human pancreatic cancers. In the present study, we co-expressed the two tumor suppressive molecules with a '2A peptide' linker, which guaranteed the two molecules were transcribed into one mRNA, whereas they were translated into two separate proteins, in pancreatic cancer Panc-1 cells, and investigated the inhibition of the two molecules on the proliferation and migration of Panc-1 cells. Results demonstrated that, either overexpression of FOXL1 or PP2A via adenovirus significantly inhibited the proliferation of Panc-1 cells, whereas promoted apoptosis in such cells. Moreover, the co-expression of both FOXL1 and PP2A exerted synergistic antitumor effect in Panc-1 cells, with significantly higher proliferation inhibition and tumor induction. In addition, we found that the overexpressed FOXL1 promoted the TNF-related apoptosis-inducing ligand (TRAIL), whereas the overexpressed PP2A downregulated the phosphorylation of c-MYC. The co-expression of FOXL1 and PP2A presented both functions in Panc-1 cells. In conclusion, the adenovirus-mediated co-expression of FOXL1 and PP2A with the 2A peptide linker exterts synergistic suppression of pancreatic cancer cells via inhibiting the growth and promoting apoptosis of cancer cells, probably via upregulating TRAIL and reducing the phosphorylation of MYC. PMID- 26820811 TI - Erratum to: Pharmacoeconomic effect of compliance with pharmacist's intervention based on cancer chemotherapy regimens: a cohort study. AB - [This corrects the article DOI: 10.1186/s40780-014-0007-y.]. PMID- 26820813 TI - Compassion, prejudice, and mental health nursing: 14 years on. PMID- 26820814 TI - Reply. PMID- 26820815 TI - Aquaporin 3 protects against lumbar intervertebral disc degeneration via the Wnt/beta-catenin pathway. AB - Previous studies have demonstrated that the expression of aquaporin 3 (AQP3), a water channel which promotes glycerol permeability and water transport across cell membranes, is reduced in degenerative lumbar intervertebral disc (IVD) tissues. However, the role of AQP3 in the pathogenesis of IVD degeneration has not recieved much scholarly attention. The objective of the present study was to investigate the effect of AQP3 on cell proliferation and extracellular matrix (ECM) degradation in human nucleus pulposus cells (hNPCs) using gain-of-function and loss-of-function experiments, and to determine whether Wnt/beta-catenin signaling is involved in the effect of AQP3 on IVD degeneration. hNPCs were transfected with the AQP3-pcDNA3.1 plasmid or AQP3 siRNA to overexpress or suppress AQP3. An MTT assay was performed to determine cell proliferation, and we found that AQP3 promoted hNPC proliferation. The expression of aggrecan, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4 and ADAMTS5 was detected using western blot analysis, to examine the effect of AQP3 on ECM degradation in hNPCs. The results revealed that AQP3 inhibited ECM degradation in hNPCs. In addition, we found that Wnt/beta-catenin signaling was suppressed by AQP3. However, the effect of AQP3 on hNPC proliferation and ECM degradation was reversed by treatment with lithium chloride, a known activator of Wnt/beta-catenin signaling. In conclusion, using in vitro and in vivo tests, we have reported for the first time, to the best of our knowledge, that AQP3 exerts protective effects against IVD degeneration, and these are effected, at least partially, through the inhibition of Wnt/beta-catenin signaling. PMID- 26820817 TI - Hazardous drinking and weight-conscious drinking behaviors in a sample of college students and college student athletes. AB - BACKGROUND: "Weight-conscious drinking" refers to behaviors to restrict calories in conjunction with consuming alcohol and is associated with numerous negative consequences. This behavior has been observed in the college student population but has not been examined among college student athletes. METHODS: This cross sectional study assessed drinking, hazardous drinking levels (Alcohol Use Disorders Identification Test-Consumption [AUDIT-C] sum score), and weight conscious drinking behaviors (for weight loss purposes and for intoxication purposes) using a paper-and-pencil survey that was completed by students at a large, private university in the Southwest United States. The sample for this study included college student nonathletes (n = 482; 212 males and 270 females) who completed the survey in 1 of 34 classes and college student athletes (n = 201; 79 males and 122 females) who completed the survey during practice. These analyses examined whether hazardous drinking level and other personal covariates (gender, race, and athlete status) predicted the 2 weight-conscious drinking behaviors of interest. RESULTS: Among the subsample of students who drank, the same proportion of participants indicated weight-conscious drinking behavior for weight loss and weight-conscious drinking behavior for intoxication (both 24.9%; n = 122). In the multivariate analyses, students with higher hazardous drinking scores and females were significantly more likely to report engaging in both weight-conscious drinking behaviors. In those analyses, neither weight-conscious drinking behavior varied by athlete status. CONCLUSIONS: In this sample of college students, hazardous drinking most predicted weight-conscious drinking behavior and superseded gender and athlete status. In response, college health professionals should consider evidenced-based approaches to address hazardous drinking. PMID- 26820819 TI - Convergence Properties of Certain Minres Algorithms. AB - Levin (1988) has challenged the convergence properties of the Harman and Jones (1966) method of Minres factor analysis. Levin claimed that convergence of the Harman and Jones method is not guaranteed and that a modified version of this method, with proven convergence, is to be preferred. In the present article it is shown that both claims are invalid. Monotone convergence of the Harman and Jones method is guaranteed whereas the modified version, proposed by Levin, may converge to an incorrect solution. Levin has also claimed that the rank-one version of the Harman and Jones method, as implemented in a method by Zegers and ten Berge (1983) lacks a valid convergence proof, and that a method suggested by Comrey and Ahumada (1964, 1965) should be used instead. It is shown that these claims, too, should be reversed. PMID- 26820816 TI - Clinical features and survival in individuals with trisomy 18: A retrospective one-center study of 44 patients who received intensive care treatments. AB - Trisomy 18 syndrome is a common autosomal aneuploidy chromosomal abnormality caused by the presence of extra chromosome 18 that leads to malformations of various parts of the body. In this study, we retrospectively investigated the effect of the medical progression and prognosis of 44 cases of trisomy 18, admitted to our neonatal intensive care unit between 1992 and 2013. The patients were divided into group A (n=20, 1992-2002) and group B (n=24, 2003-2012). Following delivery, karyotype, gender, gestational weeks, birth place, cesarean section, Apgar score and birth weight were analyzed using the Fisher's exact test, unpaired t-test and Mann-Whitney U test. Based on the statistical results, a comparison was made of the two groups and no significant differences were observed. Clinical data of major complications, mechanical ventilation, discharge from hospital and survival days were reviewed for the cases of trisomy 18. Of the 44 patients, 42 had cardiac anomaly, 16 had esophageal atresia, and 3 patients had brain anomaly. Ventilation treatment was performed in 29 cases (65.9%) and an increased percentage was identified in group B patients. The percentage survival was estimated using Kaplan-Meier curves and the two groups were analyzed using the generalized Wilcoxon test. Improvement in life prognosis was observed in group B as compared to group A. The log-rank test was used to assess survey periods of 180 days, 1 year, and the entire observation period. Although significant differences were observed for the prognosis of trisomy 18 at 180 days after birth, after 1 year and the entire survey period after birth, the significant differences were not confirmed. In conclusion, results of the present study provide information concerning genetic counseling for parents/guardians and life prognosis, prior to applying intensive management to newborns with trisomy 18. PMID- 26820818 TI - Analgesic effects evoked by a CCR2 antagonist or an anti-CCL2 antibody in inflamed mice. AB - Chemokine CCL2, also known as monocyte chemoattractant protein-1 (MCP-1), is a molecule that in addition to its well-established role in chemotaxis can also act as nociceptor sensitizer. The upregulation of this chemokine in inflamed tissues could suggest its involvement in inflammatory hypernociception. Thus, we have measured CCL2 levels in mice with acute or chronic inflammation due to the intraplantar (i.pl.) injection of carrageenan or complete Freund's adjuvant (CFA), respectively, and we have studied whether inflammatory hyperalgesia or allodynia could be attenuated by blocking CCR2 receptors or neutralizing CCL2 with an anti-CCL2 antibody. A remarkable increase in CCL2 concentration was detected by ELISA in paw homogenates coming from carrageenan- or CFA-inflamed mice, being its expression mainly localized in macrophages, as shown by immunohistochemical assays. The s.c. (0.3-3 mg/kg) or i.pl. (0.3-3 MUg) administration of the CCR2 antagonist, RS 504393, dose dependently inhibited thermal hyperalgesia measured in acutely or chronically inflamed mice, whereas s.c. administration of this drug did not reduce inflammatory mechanical allodynia. Furthermore, the inhibition of inflammatory hyperalgesia after the administration of an anti-CCL2 antibody (0.1-1 MUg; i.pl.) suggests that CCL2 could be the endogenous chemokine responsible for CCR2-mediated hyperalgesic effects. Besides, the acute administration of the highest antihyperalgesic dose of RS 504393 assayed did not reduce paw tumefaction or modify the presence of inflammatory cells. These results indicate that the blockade of the CCL2/CCR2 system can counteract inflammatory hyperalgesia, being this antinociceptive effect unrelated to a decrease in the inflammatory reaction. PMID- 26820820 TI - Mathematical Programming Approaches for the Classification Problem in Two-Group Discriminant Analysis. AB - The authors introduce mathematical programming formulations as new approaches to solve the classification problem in discriminant analysis. These formulations have recently emerged as powerful alternatives to the existing methods of maximizing correct classification of entities into groups. The research literature on mathematical programming formulations is reviewed and summarized. An illustration using a real-world classification problem is provided. issues relevant to potential users of these formulations as well as fruitful future research avenues are discussed. PMID- 26820821 TI - The Robustness of 2SLS Estimation of a Non-normally Distributed Confirmatory Factor Analysis Model. AB - A Monte Carlo study was conducted to assess the robustness of the limited information two-stage least squares (2SLS) estimation procedure on a confirmatory factor analysis model with non-normal distributions. Full information maximum likelihood (FIML) methods were also used for a comparison. Both procedures were used to estimate model parameters, contingent upon a design utilizing two levels of model loadings (small versus large) over four different distribution conditions (normally distributed, small asymmetry, medium asymmetry, and large asymmetry, with kurtosis held constant). One hundred model replications were conducted to generate the study data. For the model and parameters studied, results indicated both estimators were robust with respect to moderate deviations from normality. Both estimators produced similar estimates across all conditions studied, thus providing a measure of high relative efficiency for the 2SLS procedure. PMID- 26820822 TI - The Detection and Interpretation of Interaction Effects Between Continuous Variables in Multiple Regression. AB - issues in the detection and interpretation of interaction effects between quantitative variables in multiple regression analysis are discussed. Recent articles by Cronbach (1987) and Dunlap and Kemery (1987) suggested the use of two transformations to reduce "problems" of multicollinearity. These transformations are discussed in the context of the conditional nature of multiple regression with product terms. It is argued that although additive transformations do not affect the overall test of statistical interaction, they do affect the interpretational value of regression coefficients. Factors other than multicollinearity that may account for failures to observe interaction effects are noted. PMID- 26820823 TI - An Information Theoretic Approach for Identifying Shared Information and Asymmetric Relationships Among Variables. AB - Behavioral researchers are often faced with the need to identify complex multivariate relationships. Statistical information theory provides a framework for quantifying in a single value the proportion of total information in one set of measures (Y) explained by another set of measures (X). It also quantifies the amount of redundant information and allows for asymmetry of explained information between variables. The general information theoretic approach is presented and illustrated using measures of affect, cognition and behavior. A statistically significant and asymmetric information theoretic relationship is found among the variables: affect (like/dislike) provides a higher percentage of information about behavior (shopping frequency) than behavior does about affect. In addition, affect provides a higher percentage of information about behavior than does perceived location convenience. PMID- 26820824 TI - Characterizing Bacteriophage PR772 as a Potential Surrogate for Adenovirus in Water Disinfection: A Comparative Analysis of Inactivation Kinetics and Replication Cycle Inhibition by Free Chlorine. AB - Elucidating mechanisms by which pathogenic waterborne viruses become inactivated by drinking water disinfectants would facilitate the development of sensors to detect infectious viruses and novel disinfection strategies to provide safe water. Using bacteriophages as surrogates for human pathogenic viruses could assist in elucidating these mechanisms; however, an appropriate viral surrogate for human adenovirus (HAdV), a medium-sized virus with a double-stranded DNA genome, needs to be identified. Here, we characterized the inactivation kinetics of bacteriophage PR772, a member of the Tectiviridae family with many similarities in structure and replication to HAdV. The inactivation of PR772 and HAdV by free chlorine had similar kinetics that could be represented with a model previously developed for HAdV type 2 (HAdV-2). We developed and tested a quantitative assay to analyze several steps in the PR772 replication cycle to determine if both viruses being inactivated at similar rates resulted from similar replication cycle events being inhibited. Like HAdV-2, we observed that PR772 inactivated by free chlorine still attached to host cells, and viral DNA synthesis and early and late gene transcription were inhibited. Consequently, free chlorine exposure inhibited a replication cycle event that was post-binding but took place prior to early gene synthesis for both PR772 and HAdV-2. PMID- 26820826 TI - Prior Cannabis Use Is Associated with Outcome after Intracerebral Hemorrhage. AB - OBJECTIVE: Recent evidence suggests that a potential harmful relationship exists between cannabis use and ischemic stroke. The purpose of this study was to determine the implications of cannabis use in intracerebral hemorrhage (ICH) patients. METHODS: An analysis of an international, multicenter, observational database of consecutive patients with spontaneous ICH was conducted. We extracted the following characteristics on presentation: demographics, risk factors, antiplatelet or anticoagulant use, Glasgow Coma Scale, ICH score, neuroimaging parameters, and urine toxicology screen (UTS) results. Modified Rankin Scale (mRS) score was utilized for determination of outcome at discharge. Adjusted logistic ordinal regression was used as shift analysis to assess the impact of cannabis use on mRS score at discharge. The adjusted common OR measured the likelihood that cannabis use would lead to lower mRS scores. RESULTS: Within a cohort of 725 spontaneous ICH patients, UTS was positive for cannabinoids in 8.6%. Cannabinoids-positive (CB+) patients were more frequently Caucasian (p < 0.001), younger (p < 0.001), and had lower median ICH scores on admission (p = 0.017) than those who were cannabinoids-negative. CB+ patients also showed a shift toward better outcome in the distribution of mRS categories, with an adjusted common OR of 0.544 (95% CI 0.330-0.895, p = 0.017). CONCLUSION: In this multinational cohort, cannabis use was discovered in nearly 10% of patients with spontaneous ICH. Although there was no relationship between cannabis use and specific ICH characteristics, CB+ patients had milder ICH presentation and less disability at discharge. PMID- 26820827 TI - The presence of serotonin in cigarette smoke - a possible mechanistic link to 5 HT-induced airway inflammation. AB - We previously reported the involvement of serotonin (5-HT) metabolism in cigarette smoke-induced oxidative stress in rat lung in vivo. Here, we report cigarette smoke as a source of serotonin (5-HT) to the airways and aim at investigating the effects of 5-HT on oxidative stress and inflammation in human bronchial epithelial cells (BEAS-2B). A 5-HT analog was identified to be present in aqueous phase cigarette smoke using the LC-MS/MS approach, which was later confirmed by a 5-HT enzyme-linked immune assay (EIA). Furthermore, exposure to 5 HT caused a time-dependent elevation of intracellular ROS level, which was blocked in the presence of apocynin (a NOX inhibitor). In support, the immunoblot analysis indicated that there was an increase in the expression of NOX2 time dependently. 5-HT-induced elevation of IL-8 at both mRNA and protein levels was observed, which was inhibited by TEMPOL (a free radical scavenger), and inhibitors for p38 MAPK (SB203580) and ERK (U0126), in line with the time dependent phosphorylation of p38 MAPK and ERK. In conclusion, our findings suggest that 5-HT presented in bronchial epithelium of smokers may be involved in cigarette smoke-induced oxidative stress and inflammation via activation of p38 MAPK and ERK pathway after the formation of free radicals. PMID- 26820828 TI - [Relationships between venomous function and innate immune function]. AB - Venomous function is investigated in relation to innate immune function in two cases selected from scorpion venom and serpent venom. In the first case, structural analysis of scorpion toxins and defensins reveals a close interrelation between both functions (toxic and innate immune system function). In the second case, structural and functional studies of natural inhibitors of toxic snake venom phospholipases A2 reveal homology with components of the innate immune system, leading to a similar conclusion. Although there is a clear functional distinction between neurotoxins, which act by targeting membrane ion channels, and the circulating defensins which protect the organism from pathogens, the scorpion short toxins and defensins share a common protein folding scaffold with a conserved cysteine-stabilized alpha-beta motif of three disulfide bridges linking a short alpha helix and an antiparallel beta sheet. Genomic analysis suggests that these proteins share a common ancestor (long venom toxins were separated from an early gene family which gave rise to separate short toxin and defensin families). Furthermore, a scorpion toxin has been experimentally synthetized from an insect defensin, and an antibacterial scorpion peptide, androctonin (whose structure is similar to that of a cone snail venom toxin), was shown to have a similar high affinity for the postsynaptic acetylcholine receptor of Torpedo sp. Natural inhibitors of phospholipase A2 found in the blood of snakes are associated with the resistance of venomous snakes to their own highly neurotoxic venom proteins. Three classes of phospholipases A2 inhibitors (PLI alpha, PLI-beta, PLI-gamma) have been identified. These inhibitors display diverse structural motifs related to innate immune proteins including carbohydrate recognition domains (CRD), leucine rich repeat domains (found in Toll-like receptors) and three finger domains, which clearly differentiate them from components of the adaptive immune system. Thus, in structure, function and phylogeny, venomous function in both vertebrates and invertebrates are clearly interrelated with innate immune function. PMID- 26820829 TI - [Anti-platelets without a bleeding risk: novel targets and strategies]. AB - Anti-platelet agents such as aspirin, clopidogrel and antagonists of integrin alphaIIbbeta3 allowed to efficiently reduce morbidity and mortality associated with arterial thrombosis. A major limit of these drugs is that they increase the risk of bleeding. During the last few years, several innovative anti-thrombotic strategies with a potentially low bleeding risk were proposed. These approaches target the collagen receptor glycoprotein (GP) VI, the GPIb/von Willebrand factor axis, the thrombin receptor PAR-1, the activated form of integrin alphaIIbbeta3 or the ADP receptor P2Y1. While an antagonist of PAR-1 was recently marketed, the clinical proofs of the efficiency and safety of the other agents remain to be established. This review evaluates these new anti-platelet approaches toward safer anti-thrombotic therapies. PMID- 26820830 TI - [Brain and memory: new neurons to remember]. AB - A defining characteristic of the brain is its remarkable capacity to undergo activity-dependent functional and structural remodelling via mechanisms of plasticity that form the basis of our capacity to encode and retain memories. The prevailing model of how our brain stores new information about relationships between events or new abstract constructs suggests it resides in activity-driven modifications of synaptic strength and remodelling of neural networks brought about by cellular and molecular changes within the neurons activated during learning. To date, the idea that a form of activity-dependent synaptic plasticity known as long-term potentiation, or LTP, and the associated synaptic growth play a central role in the laying down of memories has received considerable support. Beyond this mechanism of plasticity at the synapse, adult neurogenesis, i.e. the birth and growth of new neurons, is another form of neural plasticity that occurs continuously in defined brain regions such as the dentate gyrus of the hippocampus. Here, based on work in the hippocampus, we review the processes and mechanisms of the generation and selection of new neurons in the adult brain and the accumulating evidence that supports the idea that this form of neural plasticity is essential to store and lead to retrievable hippocampal-dependent memories. PMID- 26820831 TI - [Cognitive and brain development of memory from infancy to early adulthood]. AB - Cognitive and brain development are closely linked from infancy to adulthood. The purpose of this article is to review the current state of knowledge on behavioral and brain substrates of memory development. First, we will review cognitive development of different memory systems, from procedural to autobiographical memory. We will discuss how the development of other cognitive functions (language, attention, executive functions and metamemory) participates in memory development. Second, we will describe how structural and functional changes in two core brain regions of memory, i.e. the hippocampus and the prefrontal cortex, impact the protracted development of memory throughout childhood. PMID- 26820832 TI - [The role of sleep in memory consolidation: effects of age and Alzheimer's disease]. AB - Sleep favors memory consolidation. Studies conducted in recent years allowed to reveal the neurobiological underpinnings underlying the beneficial effect of sleep on memory. They also have led to the proposal of two theoretical models: the "hippocampo-neocortical dialogue" and the "synaptic downscaling hypothesis". Normal ageing and, even more markedly Alzheimer's disease, are associated with sleep changes that may alter sleep-dependent memory consolidation. This paper presents a review of studies investigating the relationships between sleep and memory and how these links are affected by ageing and Alzheimer's disease. PMID- 26820833 TI - [Neuroscience and collective memory: memory schemas linking brain, societies and cultures]. AB - During the last two decades, the effect of intersubjective relationships on cognition has been an emerging topic in cognitive neurosciences leading through a so-called "social turn" to the formation of new domains integrating society and cultures to this research area. Such inquiry has been recently extended to collective memory studies. Collective memory refers to shared representations that are constitutive of the identity of a group and distributed among all its members connected by a common history. After briefly describing those evolutions in the study of human brain and behaviors, we review recent researches that have brought together cognitive psychology, neuroscience and social sciences into collective memory studies. Using the reemerging concept of memory schema, we propose a theoretical framework allowing to account for collective memories formation with a specific focus on the encoding process of historical events. We suggest that (1) if the concept of schema has been mainly used to describe rather passive framework of knowledge, such structure may also be implied in more active fashions in the understanding of significant collective events. And, (2) if some schema researches have restricted themselves to the individual level of inquiry, we describe a strong coherence between memory and cultural frameworks. Integrating the neural basis and properties of memory schema to collective memory studies may pave the way toward a better understanding of the reciprocal interaction between individual memories and cultural resources such as media or education. PMID- 26820834 TI - [Memory processes and executive functioning: novel trends for research]. AB - The existence of processes common to memory systems and executive functioning was evidenced by studies in the domain of cerebral neuroimaging, individual differences (mainly in normal aging) and, to a lesser extent, neuropsychology. Executive functioning depends on a large antero-posterior brain network, some regions of which (the middle dorsolateral and ventrolateral cortex, the dorsal anterior cingulate cortex) are involved in a series of executive processes, but also in encoding and retrieval of information in episodic memory and short-term memory. A consequence of lesions in frontal areas is to impair strategical organization of the information to-be-processed (an executive process) and thus leads to a lower memory capacity in frontal patients. Moreover, executive abilities will influence both memory efficiency and the associated brain networks even in people without brain pathology. These data attest to the importance of the relationships between executive and memory processes for an optimal cognitive functioning. Recent advances in neuroimaging and electrophysiology data acquisition and analysis techniques should allow us to better determine and understand the fashion in which these relationships work. PMID- 26820835 TI - Delivery prediction in pregnant women with spontaneous preterm birth using fetal adrenal gland biometry. AB - OBJECTIVE: To assess the prediction of delivery within 7 days in pregnant women who showed symptoms of spontaneous preterm birth (PB) by means of fetal adrenal gland biometry and to compare these predictions with the cervical length (CL) measurement. METHODS: We performed a prospective cross-sectional study with 53 pregnant women between 24 and 36 weeks of gestation. An ultrasound exam was performed for each participant to obtain the CL measurement (transvaginal route) and fetal adrenal gland biometry on day 1 of their hospital admission because of symptoms of spontaneous PB. The main outcome measure was the time between the ultrasound exam and delivery, which was classified into two groups: delivery <=7 days and delivery >7 days. A receiver operating characteristics (ROC) curve was performed to define the cutoffs for sensitivity and specificity. RESULTS: The prevalence of delivery within 7 days was 35.8%, which showed a statistically significant difference from the depth of the central zone of the fetal adrenal gland (p = 0.036). The cutoff for the depth of the central zone of the fetal adrenal gland was 7.2 mm (sensitivity 66.7%, specificity 61.8% and accuracy 63.5%). These values were not significantly different than the cutoffs for cervical length measurement: 20 mm (p = 0.267) and 9 mm (p = 0.118). CONCLUSION: The biometry for the central zone of the fetal adrenal gland predicted delivery within 7 days in pregnant women with spontaneous PB and had a predictive accuracy similar to that of CL measurement. PMID- 26820836 TI - Erratum. PMID- 26820837 TI - Pauci-immune glomerulonephritis: the ANCA-negative side of the coin. PMID- 26820838 TI - Evaluation of interferon-gamma release assay (T-SPOT.TB(TM) ) for diagnosis of tuberculosis infection in rheumatic disease patients. AB - AIM: Patients with rheumatic diseases are at higher risk of developing tuberculosis (TB). The objective of this prospective study was to evaluate the T SPOT.TB assay (T cell enzyme-linked immuno-spot assay), for the diagnosis of tuberculosis infection in rheumatic disease patients in China. METHODS: Prospectively enrolled patients came from the Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine between July 2008 and Aug 2012 for TB screening. Subjects' histories of TB infection, previous TB contact or bacille Calmette-Guerin vaccination and concurrent immunosuppressive therapy, were reviewed carefully and recorded in detail. TST (tuberculin skin test) and TSPOT.TB assay were performed on the subjects. A prospective evaluation by Chi-square test was used for sensitivity and specificity of both TST and T SPOT assay. RESULTS: A total of 311 subjects included 114 (36.66%) male and 197 (63.34%) female subjects, with a median age of 37.7 +/- 12.6 years (range 17-72). Thirty-two patients (10.29%) had a history of TB infection or previous TB contact; 256 patients (82.32%) were using glucocorticoids or immunosuppressants; 28 patients (9.0%) were clinically diagnosed as having TB infection. The sensitivity and specificity of TST for TB screening in rheumatic disease patients was 81.82% (9/11) and 67% (67/100), respectively. However, the sensitivity and specificity of T-SPOT assay was statistically higher at 92.86% (26/28) and 93.64% (265/283), respectively (P < 0.05). CONCLUSION: As a new immunoassay for TB diagnosis, the sensitivity and specificity of T-SPOT is higher than TST. It is of great importance in the diagnosis of active or latent TB infection in rheumatic disease patients. PMID- 26820839 TI - Determining the necessity for right heart catheterization in pulmonary hypertension associated with connective tissue diseases assessed by echocardiography. AB - AIM: The prognosis of pulmonary hypertension (PH) in systemic sclerosis (SSC) and in systemic lupus erythematosus (SLE) is different. According to the guidelines, right heart catheterization (RHC) is necessary in pulmonary arterial hypertension (PAH) associated with connective tissue diseases (CTD). However, there is little supporting evidence. Therefore, we attempted to determine the necessity for RHC and the causes of differences in prognosis of PH by comparing SSC to SLE. METHODS: The inclusion criteria were all patients with SSC or SLE with exertional dyspnea. Echocardiography and carotid Doppler ultrasound were performed. RESULTS: Twenty-three patients with SSC and 23 with SLE participated in this study. There was no difference in the right ventricular systolic pressure (RVSP) between SSC and SLE (33.0 mmHg, range 25.3-41.7 mmHg vs. 32.4 mmHg, range 27.0-37.7 mmHg; P = 0.835). In multiple linear regression analysis, the ratio of peak tricuspid regurgitant velocity to right ventricular outflow tract time-velocity integral, which represents pulmonary vascular resistance (PVR), was correlated with RVSP in SSC (r(2) = 0.928, beta = 0.362, P = 0.003), and the independent predictor of increased RVSP was the ratio of early diastolic transmitral filling velocity to early diastolic septal mitral annular velocity, which represents diastolic dysfunction in SLE (R(2) = 0.806, beta = 0.803, P = 0.023). CONCLUSIONS: PVR was an important cause of PH in SSC. Left ventricular dysfunction was an important cause of PH in SLE. Thus, these findings demonstrate the necessity for RHC and differences in prognosis of PH in CTD. PMID- 26820841 TI - Family matters: Directionality of turning bias while kissing is modulated by context. AB - When leaning forward to kiss to a romantic partner, individuals tend to direct their kiss to the right more often than the left. Studies have consistently demonstrated this kissing asymmetry, although other factors known to influence lateral biases, such as sex or situational context, had yet to be explored. The primary purpose of our study was to investigate if turning direction was consistent between a romantic (parent-parent) and parental (parent-child) kissing context, and secondly, to examine if sex differences influenced turning bias between parent-child kissing partners. An archival analysis coded the direction of turning bias for 161 images of romantic kissing (mothers kissing fathers) and 529 images of parental kissing (mothers or fathers kissing sons or daughters). The results indicated that the direction of turning bias differed between kissing contexts. As expected, a right-turn bias was observed for romantic kissing; however, a left-turn bias was exhibited for parental kissing. There was no significant difference of turning bias between any parent-child kissing partners. Interpretations for the left-turn bias discuss parental kissing as a learned lateral behaviour. PMID- 26820840 TI - Distinct gene expression profiles provoked by polyacrylamide beads (Biogel) during chronic and acute inflammation in mice selected for maximal and minimal inflammatory responses. AB - OBJECTIVE AND DESIGN: AIRmax and AIRmin mice differ in their local acute inflammatory reactions to polyacrylamide beads (Biogel). These lines were developed to identify genes that affect the intensity of the acute inflammatory response (AIR) and to investigate the cellular and molecular mechanisms of acute inflammation. Although these lines are well established, differences in their responses to chronic inflammatory Biogel exposure have not yet been described. We investigated whether the selective process that modified the acute inflammatory responses in these animals also affected the development of their chronic inflammatory responses. RESULTS: Inflammatory exudate cell infiltration was more intense in AIRmax than AIRmin mice at both 48 h and 30 days. Genes involved in signal transduction and immune/inflammatory responses were differentially expressed in the treated skin of AIRmax and AIRmin mice, and divergent expression of some acute inflammatory response genes was detected up to 30 days post-Biogel. However, distinct expression of several pro and anti-inflammatory response genes in both periods was observed. CONCLUSION: These results indicate that the selective process for acute inflammation affected the development of chronic inflammatory responses to Biogel, suggesting common genetic control. PMID- 26820842 TI - Toxicity and inflammatory response in Swiss albino mice after intraperitoneal and oral administration of polyurethane nanoparticles. AB - In this work in vivo experiments were conducted in order to characterize the biocompatibility of polyurethane nanoparticles (PU-NPs) after intraperitoneal (i.p.) and oral administration. Additionally, ex vivo assays were performed to assess human blood compatibility as well as in vitro assays to assess protein binding. Our results indicated that administration of three different concentrations of PU-NPs induced a significant increase in visceral fat accumulation after oral dosing. In addition, fat tissue of mice intraperitoneally treated with the highest concentration of nanoparticles showed diffuse mononuclear inflammatory infiltrate in the fat tissue. Histopathological assessment showed inflammatory infiltrate and hepatocyte vacuolization in the liver, inflammatory infiltration and vascular congestion in the lung and glomerular necrosis in the kidney. Hepatic enzymes related with liver function were significantly increased in both groups of mice treated with PU-NPs. The PU NPs did not affect the human blood cells number as well as coagulation time but showed a susceptibility to bind in proteins commonly found in the blood stream. In addition, increased amounts of pro inflammatory cytokines in vivo, as well as ex vivo in human cells were observed. Further studies to establish the consequences of long-term exposure to PU-NPs are warranted. PMID- 26820843 TI - Kinetically "locked" metallomacrocycle. AB - Self-assembly based on reversible metal-ligand bond formation is useful for the synthesis of discrete supramolecular nanoarchitectures. However, the architectures constructed by this technique sometimes suffer from kinetic instability due to the dissociation of metal-ligand bonds, especially under highly diluted conditions or in the presence of competitive ligands or metal ions. In this study, a kinetically stabilized metallomacrocycle was synthesized in one pot via the combination of metal-mediated self-assembly and subsequent oxidative "locking" of the coordination bonds. The macrocycle consists of four Co ions and four bis-bidentate ligands L(2-). The complexation of labile Co(II) ions with the ligands afforded the macrocycle with four-fold rotational symmetry, exhibiting the right-angled geometries of the beta-diketonate ligands on the carbazole. The subsequent oxidation of the Co(II) ions inside the macrocycle into Co(III) ions made the metal-ligand bonds almost inert, thus affording a kinetically locked 4 : 4 metallomacrocycle. This macrocycle showed high stability even in the presence of an excess amount of competitive ligands. X-ray crystallography of the macrocycle indicated that it assembled in a columnar manner, forming one-dimensional nanochannels in the middle of the column. PMID- 26820844 TI - Report of novel genetic variation in NPHS2 gene associated with idiopathic nephrotic syndrome in South Indian children. AB - BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is found in 10-20 % of children with idiopathic nephrotic syndrome (INS). In SRNS patients, common histopathological subtypes are Focal segmental glomerulosclerosis (FSGS) (53 %) and minimal change disease (MCD) (27 %). Familial forms of FSGS constitute podocyte diseases with varying severity and age of onset. Podocin gene (NPHS2) mutations cause childhood-onset steroid-resistant FSGS and MCD to adult-onset FSGS. In view of genetic variations and susceptibility to the disease, the present investigation was undertaken to study the pattern of genetic mutation in children from South India. METHODS: Mutation analysis was carried out by direct sequencing of the entire NPHS2 gene (eight exons) using specific primers in 200 INS (100 SRNS and 100 steroid sensitive) children and 100 healthy controls. The allele and genotype frequencies of NPHS2 gene were calculated for both cases and controls as per Hardy-Weinberg equilibrium. RESULTS: Among the SRNS patients, 18 % revealed both heterozygous and homozygous mutations. Out of 12 mutations, 8 were homozygous and 4 were heterozygous. Interestingly, we found two novel SNPs in exon 4 of NPHS2 gene, which are documented and submitted to dbsnp database (Ref rs12401711 and rs12401708). CONCLUSION: Mutational analysis of NPHS2 would be advisable at the start of treatment. The genetic variations detected in the study would serve as the important molecular marker in treating the children's at early stage, which also enables to detect carriers, prenatal diagnosis and provide genetic counseling to couples at risk. PMID- 26820845 TI - The association of hypercalciuria and hyperuricosuria with vesicoureteral reflux in children. AB - OBJECTIVES: One of the important complications of vesicoureteral reflux (VUR) is the development of urolithiasis. Identifying factors involved in development of urolithiasis in children with VUR is immensely important. This study was conducted to determine the association between hypercalciuria and hyperuricosuria with VUR in children. METHODS: One-hundred children with VUR (case group) were compared to 100 healthy children (control group) in terms of hypercalciuria and hyperuricosuria. To measure these markers, random morning fasting urine samples were used. Data were analyzed using statistical tests. RESULTS: Hypercalciuria and hyperuricosuria frequencies, and also urine calcium/creatinine (Ca/Cr) and urine uric acid/creatinine (UA/Cr) ratios were significantly higher in the case group compared to the control group (P < 0.05). A significant difference was found between hypercalciuria and hyperuricosuria in severity of VUR (P < 0.05). A positive correlation was observed between hypercalciuria and hyperuricosuria and severity of VUR (P < 0.05). CONCLUSIONS: The present study showed that there is association between hypercalciuria, hyperuricosuria and VUR in children. It is recommended to adopt measures to prevent the development of urolithiasis in VUR patients. PMID- 26820846 TI - Explaining Spatial Variation in the Recording Effort of Citizen Science Data across Multiple Taxa. AB - The collation of citizen science data in open-access biodiversity databases makes temporally and spatially extensive species' observation data available to a wide range of users. Such data are an invaluable resource but contain inherent limitations, such as sampling bias in favour of recorder distribution, lack of survey effort assessment, and lack of coverage of the distribution of all organisms. Any technical assessment, monitoring program or scientific research applying citizen science data should therefore include an evaluation of the uncertainty of its results. We use 'ignorance' scores, i.e. spatially explicit indices of sampling bias across a study region, to further understand spatial patterns of observation behaviour for 13 reference taxonomic groups. The data is based on voluntary observations made in Sweden between 2000 and 2014. We compared the effect of six geographical variables (elevation, steepness, population density, log population density, road density and footpath density) on the ignorance scores of each group. We found substantial variation among taxonomic groups in the relative importance of different geographic variables for explaining ignorance scores. In general, road access and logged population density were consistently important variables explaining bias in sampling effort, indicating that access at a landscape-scale facilitates voluntary reporting by citizen scientists. Also, small increases in population density can produce a substantial reduction in ignorance score. However the between-taxa variation in the importance of geographic variables for explaining ignorance scores demonstrated that different taxa suffer from different spatial biases. We suggest that conservationists and researchers should use ignorance scores to acknowledge uncertainty in their analyses and conclusions, because they may simultaneously include many correlated variables that are difficult to disentangle. PMID- 26820847 TI - Motor and somatosensory evoked potential spinal cord monitoring during intubation and neck extension for thyroidectomy in a Down syndrome boy with atlantoaxial instability. AB - Intubation or neck extension can compress the spinal cord in patients with craniocervical instability. Protective motor evoked potential (MEP) and somatosensory evoked potential (SEP) monitoring of these maneuvers is an obvious consideration when these patients undergo already-monitored spinal surgery, but might be overlooked when they undergo other normally unmonitored procedures. Here we report monitoring intubation and neck extension for the unusual indication of thyroidectomy in a Down syndrome boy with atlantoaxial instability. Transcranial electric stimulation thenar MEPs and optimized median nerve SEPs were acquired about every minute throughout intubation and neck extension under propofol and remifentanil anesthesia without neuromuscular blockade. Potentials were stable and there was no neurologic deficit. This approach could protect craniocervical instability patients against cord compression when they undergo intubation and neck extension for surgical procedures that would not otherwise indicate spinal cord monitoring. PMID- 26820848 TI - Axonal transport and secretion of fibrillar forms of alpha-synuclein, Abeta42 peptide and HTTExon 1. AB - Accruing evidence suggests that prion-like behavior of fibrillar forms of alpha synuclein, beta-amyloid peptide and mutant huntingtin are responsible for the spread of the lesions that characterize Parkinson disease, Alzheimer disease and Huntington disease, respectively. It is unknown whether these distinct protein assemblies are transported within and between neurons by similar or distinct mechanisms. It is also unclear if neuronal death or injury is required for neuron to-neuron transfer. To address these questions, we used mouse primary cortical neurons grown in microfluidic devices to measure the amounts of alpha-synuclein, Abeta42 and HTTExon1 fibrils transported by axons in both directions (anterograde and retrograde), as well as to examine the mechanism of their release from axons after anterograde transport. We observed that the three fibrils were transported in both anterograde and retrograde directions but with strikingly different efficiencies. The amount of Abeta42 fibrils transported was ten times higher than that of the other two fibrils. HTTExon1 was efficiently transported in the retrograde direction but only marginally in the anterograde direction. Finally, using neurons from two distinct mutant mouse strains whose axons are highly resistant to neurodegeneration (Wld(S) and Sarm1(-/-)), we found that the three different fibrils were secreted by axons after anterograde transport, in the absence of axonal lysis, indicating that trans-neuronal spread can occur in intact healthy neurons. In summary, fibrils of alpha-synuclein, Abeta42 and HTTExon1 are all transported in axons but in directions and amounts that are specific of each fibril. After anterograde transport, the three fibrils were secreted in the medium in the absence of axon lysis. Continuous secretion could play an important role in the spread of pathology between neurons but may be amenable to pharmacological intervention. PMID- 26820849 TI - Associations between Self-Reported Gastrointestinal Illness and Water System Characteristics in Community Water Supplies in Rural Alabama: A Cross-Sectional Study. AB - BACKGROUND: Community water supplies in underserved areas of the United States may be associated with increased microbiological contamination and risk of gastrointestinal disease. Microbial and health risks affecting such systems have not been systematically characterized outside outbreak investigations. The objective of the study was to evaluate associations between self-reported gastrointestinal illnesses (GII) and household-level water supply characteristics. METHODS: We conducted a cross-sectional study of water quality, water supply characteristics, and GII in 906 households served by 14 small and medium-sized community water supplies in Alabama's underserved Black Belt region. RESULTS: We identified associations between respondent-reported water supply interruption and any symptoms of GII (adjusted odds ratio (aOR): 3.01, 95% confidence interval (CI) = 1.65-5.49), as well as low water pressure and any symptoms of GII (aOR: 4.51, 95% CI = 2.55-7.97). We also identified associations between measured water quality such as lack of total chlorine and any symptoms of GII (aOR: 5.73, 95% CI = 1.09-30.1), and detection of E. coli in water samples and increased reports of vomiting (aOR: 5.01, 95% CI = 1.62-15.52) or diarrhea (aOR: 7.75, 95% CI = 2.06-29.15). CONCLUSIONS: Increased self-reported GII was associated with key water system characteristics as measured at the point of sampling in a cross-sectional study of small and medium water systems in rural Alabama in 2012 suggesting that these water supplies can contribute to endemic gastro-intestinal disease risks. Future studies should focus on further characterizing and managing microbial risks in systems facing similar challenges. PMID- 26820850 TI - Correction: Variation in the Circumsporozoite Protein of Plasmodium falciparum: Vaccine Development Implications. AB - [This corrects the article DOI: 10.1371/journal.pone.0101783.]. PMID- 26820851 TI - Useful Tips, Widely Used Techniques, and Quantifying Cell Metabolic Behavior. AB - The insect cell culture/baculovirus system has three primary applications: (1) recombinant protein synthesis, (2) biopesticide synthesis, and (3) as a model system (e.g., for studying apoptosis). The fundamental techniques involved in these applications are described throughout this book. In this chapter the most widely used techniques are summarized and the reader is directed to detailed information found elsewhere in this book. Furthermore, many useful tips and my personal preferences that are rarely published are discussed in this chapter along with quantitative methods to characterize cell growth, baculovirus infection, and metabolism. PMID- 26820852 TI - Introduction to Baculovirus Molecular Biology. AB - The development of baculovirus expression vector systems has accompanied a rapid expansion of our knowledge about the genes, their function and regulation in insect cells. Classification of these viruses has also been refined as we learn more about differences in gene content between isolates, how this affects virus structure and their replication in insect larvae. Baculovirus gene expression occurs in an ordered cascade, regulated by early, late and very late gene promoters. There is now a detailed knowledge of these promoter elements and how they interact first with host cell-encoded RNA polymerases and later with virus encoded enzymes. The composition of this virus RNA polymerase is known. The virus replication process culminates in the very high level expression of both polyhedrin and p10 gene products in the latter stages of infection. It has also been realized that the insect host cell has innate defenses against baculoviruses in the form of an apoptotic response to virus invasion. Baculoviruses counter this by encoding apoptotic-suppressors, which also appear to have a role in determining the host range of the virus. Also of importance to our understanding of baculovirus expression systems is how the virus can accumulate mutations within genes that affect recombinant protein yield in cell culture. The summary in this chapter is not exhaustive, but should provide a good preparation to those wishing to use this highly successful gene expression system. PMID- 26820853 TI - Baculovirus Transfer Vectors. AB - The production of a recombinant baculovirus expression vector normally involves mixing infectious virus DNA with a plasmid-based transfer vector and then co transfecting insect cells to initiate virus infection. The aim of this chapter is to provide an update on the range of baculovirus transfer vectors currently available. Some of the original transfer vectors developed are now difficult to obtain but generally have been replaced by superior reagents. We focus on those that are available commercially and should be easy to locate. These vectors permit the insertion of single or multiple genes for expression, or the production of proteins with specific peptide tags that aid subsequent protein purification. Others have signal peptide coding regions permitting protein secretion or plasma membrane localization. A table listing the transfer vectors also includes information on the parental virus that should be used with each one. Methods are described for the direct insertion of a recombinant gene into the virus genome without the requirement for a transfer vector. The information provided should enable new users of the system to choose those reagents most suitable for their purposes. PMID- 26820854 TI - Recombinant Baculovirus Isolation. AB - Although there are several different methods available of making recombinant baculovirus expression vectors (reviewed in Chapter 3 ), all require a stage in which insect cells are transfected with either the virus genome alone (Bac-to Bac((r)) or BaculoDirectTM, Invitrogen) or virus genome and transfer vector. In the latter case, this allows the natural process of homologous recombination to transfer the foreign gene, under control of the polyhedrin or other baculovirus gene promoter, from the transfer vector to the virus genome to create the recombinant virus. Previously, many methods required a plaque-assay to separate parental and recombinant virus prior to amplification and use of the recombinant virus. Fortunately, this step is no longer required for most systems currently available. This chapter provides an overview of the historical development of increasingly more efficient systems for the isolation of recombinant baculoviruses (Chapter 3 provides a full account of the different systems and transfer vectors available). The practical details cover: transfection of insect cells with either virus DNA or virus DNA and plasmid transfer vector; a reliable plaque-assay method that can be used to separate recombinant virus from parental (nonrecombinant) virus where this is necessary; methods for the small-scale amplification of recombinant virus; and subsequent titration by plaque-assay or real-time polymerase chain reaction (PCR). Methods unique to the Bac-to-Bac((r)) system are also covered and include the transformation of bacterial cells and isolation of bacmid DNA ready for transfection of insect cells. PMID- 26820855 TI - Gene Expression in Mammalian Cells Using BacMam, a Modified Baculovirus System. AB - BacMams are modified baculoviruses that contain mammalian expression cassettes for gene delivery and expression in mammalian cells. BacMams have become an integral part of the recombinant mammalian gene expression toolbox in research labs worldwide. Construction of transfer vectors is straightforward using basic molecular biology protocols. Virus generation is based on common methods used with the baculovirus insect cell expression system. BacMam transduction of mammalian cells requires minimal modifications to familiar cell culture methods. This chapter highlights the BacMam transfer vector pHTBV. PMID- 26820856 TI - Available Lepidopteran Insect Cell Lines. AB - This chapter lists the known cell lines from Lepidoptera, largely based on previous compilations of insect cell lines published by W. Fred Hink. More than 320 lines from 65 species are listed. The official designation is given for each cell line as well as the species, tissue source, and, when known, the susceptibilities to baculoviruses. PMID- 26820857 TI - Lepidopteran Insect Cell Line Isolation from Insect Tissue. AB - This chapter describes procedures for initiating new cell lines from lepidopteran larval tissues and embryos. The internal morphology is described along with methods for treating excised tissues and the primary cultures. Advice on culture medium and the tissues that will provide the best chance for new cell lines is discussed. PMID- 26820858 TI - Development of Serum-Free Media for Lepidopteran Insect Cell Lines. AB - Baculovirus-based Insect Cell Technology (ICT) is widely used for the expression of recombinant heterologous proteins and baculovirus bioinsecticides, and has recently gained momentum as a commercial manufacturing platform for human and veterinary vaccines. The three key components of ICT are the Lepidopteran insect cell line, the baculovirus vector, and the growth medium. Insect cell growth media have evolved significantly in the past five decades, from basal media supplemented with hemolymph or animal serum, to highly optimized serum-free media and feeds (SFM and SFF) capable of supporting very high cell densities and recombinant protein yields. The substitution of animal sera with protein hydrolysates in SFM results in greatly reduced medium costs and much improved process scalability. However, both sera and hydrolysates share the disadvantage of lot-to-lot variability, which is detrimental to process reproducibility. Hence, the industrialization of ICT would benefit greatly from chemically defined media (CDM) for insect cells, which are not yet commercially available. On the other hand, applications such as baculovirus bioinsecticides would need truly low cost serum-free media and feeds (LC-SFM and LC-SFF) for economic viability, which require the substitution of a majority of expensive added amino acids with even higher levels of hydrolysates, hence increasing the risk of a variable process. CDM developments are anticipated to benefit both conventional and low cost ICT applications, by identifying key growth factors in hydrolysates for more targeted media and feed design. PMID- 26820859 TI - Routine Maintenance and Storage of Lepidopteran Insect Cell Lines and Baculoviruses. AB - The various methods for maintaining (i.e., subculturing, splitting, or passaging) established lepidopteran cell lines are described. Three procedures are presented that are appropriate for different cell lines dependent upon the growth characteristics (in particular, cell attachment properties) of the cells of interest. In addition to the routine maintenance of cells in active culture, methods are also described for both short-term (low temperature) and long-term (frozen in liquid nitrogen) storage of cell lines, as well as quality control procedures for the cultures. Methods for storing baculoviruses for use in cell cultures and issues of concern when using cell cultures for their production and study are also described. PMID- 26820860 TI - Small-Scale Production of Recombinant Proteins Using the Baculovirus Expression Vector System. AB - Numerous technological improvements, including progress in vector design, simplification of virus isolation techniques, and advancements in molecular biology and cell culture technologies, have greatly facilitated the use of the baculovirus-insect cell system for routine production of recombinant proteins. This chapter outlines the basic techniques for small-scale protein production using the Baculovirus Expression Vector System (BEVS), including protocols for titer estimation in 96-well plates, expression optimization in 24-well plates, and recombinant protein expression from adherent and suspension cultures in six well plates and in 50 mL insect cell cultures. PMID- 26820861 TI - Recombinant Protein Production in Large-Scale Agitated Bioreactors Using the Baculovirus Expression Vector System. AB - The production of recombinant proteins using the baculovirus expression vector system (BEVS) in large-scale agitated bioreactors is discussed in this chapter. Detailed methods of the key stages of a batch process, including host cell growth, virus stock amplification and quantification, bioreactor preparation and operation, the infection process, final harvesting, and primary separation steps for recovery of the product are presented. Furthermore, methods involved with advanced on-line monitoring and bioreactor control, which have a significant impact on the overall process success, are briefly discussed. PMID- 26820862 TI - Protein Expression in Insect and Mammalian Cells Using Baculoviruses in Wave Bioreactors. AB - Many types of disposable bioreactors for protein expression in insect and mammalian cells are now available. They differ in design, capacity, and sensor options, with many selections available for either rocking platform, orbitally shaken, pneumatically mixed, or stirred-tank bioreactors lined with an integral disposable bag (Shukla and Gottschalk, Trends Biotechnol 31(3):147-154, 2013). WAVE BioreactorsTM were among the first disposable systems to be developed (Singh, Cytotechnology 30:149-158, 1999). Since their commercialization in 1999, Wave Bioreactors have become routinely used in many laboratories due to their ease of operation, limited utility requirements, and protein expression levels comparability to traditional stirred-tank bioreactors. Wave Bioreactors are designed to use a presterilized CellbagTM, which is attached to a rocking platform and inflated with filtered air provided by the bioreactor unit. The Cellbag can be filled with medium and cells and maintained at a set temperature. The rocking motion, which is adjusted through angle and rock speed settings, provides mixing of oxygen (and CO2, which is used to control pH in mammalian cell cultures) from the headspace created in the inflated Cellbag with the cell culture medium and cells. This rocking motion can be adjusted to prevent cell shear damage. Dissolved oxygen and pH can be monitored during scale-up, and samples can be easily removed to monitor other parameters. Insect and mammalian cells grow very well in Wave Bioreactors (Shukla and Gottschalk, Trends Biotechnol 31(3):147-154, 2013). Combining Wave Bioreactor cell growth capabilities with recombinant baculoviruses engineered for insect or mammalian cell expression has proven to be a powerful tool for rapid production of a wide range of proteins. PMID- 26820863 TI - Protein Production with Recombinant Baculoviruses in Lepidopteran Larvae. AB - With an increasing need for functional analysis of proteins, there is a growing demand for fast and cost-effective production of biologically active eukaryotic proteins. The baculovirus expression vector system (BEVS) is widely used, and in the vast majority of cases cultured insect cells have been the host of choice. A low cost alternative to bioreactor-based protein production exists in the use of live insect larvae as "mini bioreactors." In this chapter we focus on Trichoplusia ni as the host insect for recombinant protein production, and explore three different methods of virus administration to the larvae. The first method is labor-intensive, as extracellular virus is injected into each larva, whereas the second lends itself to infection of large numbers of larvae via oral inoculation. While these first two methods require cultured insect cells for the generation of recombinant virus, the third relies on transfection of larvae with recombinant viral DNA and does not require cultured insect cells as an intermediate stage. We suggest that small- to mid-scale recombinant protein production (mg-g level) can be achieved in T. ni larvae with relative ease. PMID- 26820864 TI - Production of Virus-Like Particles for Vaccination. AB - The ability to make a large variety of virus-like particles (VLPs) has been successfully achieved in the baculovirus expression vector system (BEVS)/insect cell system. The production and scale-up of these particles, which are mostly sought as vaccine candidates, are currently being addressed. Furthermore, these VLPs are being investigated as delivery agents for use as therapeutics. The use of host insect cells allows mass production of VLPs in a proven scalable system. PMID- 26820865 TI - Alternative Strategies for Expressing Multicomponent Protein Complexes in Insect Cells. AB - Expression of recombinant proteins in insect cells infected with baculoviruses is commonplace. This system provides an easy way to generate a significant amount of properly folded, functional protein with proper posttranslational modifications and can be used to effectively produce multi-protein complexes. This chapter describes an alternative method of expressing high order protein complexes in insect cell culture. Specific examples involving the expression of 5- and 8 protein complexes are discussed. PMID- 26820866 TI - Transforming Lepidopteran Insect Cells for Continuous Recombinant Protein Expression. AB - The baculovirus expression vector system (BEVS) is widely used to produce large quantities of recombinant proteins. However, the yields of extracellular and membrane-bound proteins obtained with this system are often very low, possibly due to the adverse effects of baculovirus infection on the host insect cell secretory pathway. An alternative approach to producing poorly expressed proteins is to transform lepidopteran insect cells with the gene of interest under the control of promoters that are constitutively active in uninfected cells, thereby making cell lines that continuously express recombinant protein. This chapter provides an overview of the methods and considerations for making stably transformed lepidopteran insect cells. Techniques for the insertion of genes into continuous expression vectors, transfection of cells, and the selection and isolation of stably transformed Sf-9 clones by either colony formation or end point dilution are described in detail. PMID- 26820867 TI - Stable Drosophila Cell Lines: An Alternative Approach to Exogenous Protein Expression. AB - Recombinant protein production has become an indispensable tool for various research directions and biotechnological applications in the past decades. Among the numerous reported expression systems, insect cells provide the possibility to produce complex target proteins that require posttranslational modifications. Stable expression in Drosophila S2 cells represents an attractive alternative to the widely used baculovirus expression system, offering important advantages in particular for difficult-to-express proteins, e.g., membrane proteins or heavily glycosylated multi-domain proteins that are stabilized by a complex disulfide pattern. Here we present the methodology that is required for the generation of stable Drosophila S2 cell transfectants and for production of recombinant proteins using those transfectants. PMID- 26820868 TI - Transforming Lepidopteran Insect Cells for Improved Protein Processing and Expression. AB - The lepidopteran insect cells used with the baculovirus expression vector system (BEVS) are capable of synthesizing and accurately processing foreign proteins. However, proteins expressed in baculovirus-infected cells often fail to be completely processed, or are not processed in a manner that meets a researcher's needs. This chapter discusses a metabolic engineering approach that addresses this problem. Basically, this approach involves the addition of new or enhancement of existing protein processing functions in established lepidopteran insect cell lines. In addition to improvements in protein processing, this approach has also been used to improve protein expression levels obtained with the BEVS. Methods for engineering cell lines and assessing their properties as improved hosts for the BEVS are detailed. Examples of lepidopteran insect cell lines engineered for improved protein N-glycosylation, folding/trafficking, and expression are described in detail. PMID- 26820869 TI - Introduction to the Use of Baculoviruses as Biological Insecticides. AB - Baculoviruses are widely used both as protein expression vectors and as insect pest control agents. This section provides an overview of the baculovirus life cycle and use of baculoviruses as insecticidal agents. This chapter includes discussion of the pros and cons for use of baculoviruses as insecticides, and progress made in genetic enhancement of baculoviruses for improved insecticidal efficacy. These viruses are used extensively for control of insect pests in a diverse range of agricultural and forest habitats. PMID- 26820870 TI - Baculovirus Insecticide Production in Insect Larvae. AB - Baculovirus-based insecticides are currently being used worldwide, and new products are in development in many countries. The most dramatic examples of successful baculovirus insecticides are found in soybean in Brazil and cotton in China. Production of baculoviruses is generally done in larvae of a convenient host species, and the level of sophistication varies tremendously between field collection of infected insects at the one extreme and automated mass manufacturing at the other. Currently, only products with wild type baculoviruses as active ingredients are commercially available. Baculoviruses encoding insecticidal proteins are considered attractive, especially for crops with little tolerance to feeding damage, where speed-of-kill is an important characteristic. Successful field tests with such recombinant baculoviruses have been done in the past, and more tests are ongoing. However, low-cost production of recombinant baculovirus in larvae poses specific problems, due to the short survival time of the production host.In this chapter, benchtop-scale production of two typical baculoviruses is described. First, we describe the production of wild type Helicoverpa zea nucleopolyhedrovirus in bollworm (H. zea) larvae. H. zea larvae are very aggressive and need to be reared in isolation from each other. Second, we describe the production of a recombinant Autographa californica multiple nucleopolyhedrovirus in the non-cannibalistic cabbage looper, Trichoplusia ni. The recombinant baculovirus encodes the insect-specific scorpion toxin LqhIT2. The tetracycline transactivator system enables the production of wild-type quantity and quality product while toxin expression is repressed since normal toxin production would result in premature death of the production host that would limit progeny virus production. PMID- 26820871 TI - Evaluation of the Insecticidal Efficacy of Wild Type and Recombinant Baculoviruses. AB - A considerable amount of work has been undertaken to genetically enhance the efficacy of baculovirus insecticides. Following construction of a genetically altered baculovirus, laboratory bioassays are used to quantify various parameters of insecticidal activity such as the median lethal concentration (or dose) required to kill 50 % of infected larvae (LC50 or LD50), median survival of larvae infected (ST50), and feeding damage incurred by infected larvae. In this chapter, protocols are described for a variety of bioassays and the corresponding data analyses for assessment of the insecticidal activity of baculovirus insecticides. PMID- 26820872 TI - Evaluating Baculovirus Infection Using Green Fluorescent Protein and Variants. AB - By use of a strategy incorporating the green fluorescent protein (GFP), facile and rapid monitoring and visualization of baculovirus infection in insect cells is possible in vivo. This chapter describes two techniques for simple determination of virus titer in the baculovirus expression system using GFP co expression and rapid monitoring of Sf-9 insect cell infection using a combination of GFP and the early-to-late (ETL) promoter of the virus vector. Because of its early appearance, GFP, when placed under the control of ETL promoter, will facilitate vector construction, virus isolation, and titer determination. PMID- 26820873 TI - Tubular Bioreactor for Probing Baculovirus Infection and Protein Production. AB - Probing the baculovirus infection process is essential in optimizing recombinant protein production. Typically, researchers monitor the infection process in stirred reactors that contain cells that have been infected at different times after virus inoculation, particularly if cells pass the primary infection and become infected by progeny virus. This chapter describes several alternative bioreactor systems for baculovirus infection. We provide an example alternative system that holds promise to avoid asynchronous distributions in infection time. Namely, we describe a two-stage reactor system consisting of an upstream continuous stirred tank reactor and a downstream tubular reactor with segmented plug flow for probing baculovirus infection and production. PMID- 26820874 TI - Gene Silencing in Insect Cells Using RNAi. AB - A technique is described for synthesizing and transfecting double stranded RNA (dsRNA) for RNA interference (RNAi) in Sf-21 cell culture. Transfection with dsRNA only requires an hour and the cells usually recover within 12 h. Suggestions for designing dsRNA are included in the methods. Furthermore, websites are provided for rapid and effective dsRNA design. Three kits are essential for using the described methods: RNAqueous(r)-4PCR, MegascriptTM T7 kit, and the SuperscriptTM III kit from Life Technologies, Inc. PMID- 26820875 TI - Using the Baculovirus/Insect Cell System to Study Apoptosis. AB - Apoptosis is a physiological program of cell suicide conserved in invertebrates and vertebrates. Apoptosis is crucial to the normal development of organisms and in tissue homeostasis by promoting elimination of unwanted cells, including damaged or virus-infected cells. Due to the importance of programmed cell death for the survival of the organism, a tight regulation is exerted at various activation levels of the cell-death machinery. The utilization of the baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) to identify genes that inhibit the apoptotic process will be described using a transfection-based approach, illustrated by identification of the p49 gene. PMID- 26820876 TI - Generation of Envelope-Modified Baculoviruses for Gene Delivery into Mammalian Cells. AB - Genetically modified baculoviruses can efficiently deliver and express genes in mammalian cells. The major prerequisite for the expression of a gene transferred by baculovirus is its control by a promoter that is active in mammalian cells. This chapter describes methods for producing second generation baculovirus vectors through modification of their envelope. Envelope modified baculoviruses offer additional new applications of the system, such as their use in in vivo gene delivery, targeting, and vaccination. Methods of generating a recombinant baculovirus vector with a modified envelope and its amplification and purification, including technical scale production, are discussed. A variety of notes give clues regarding specific technical procedures. Finally, methods to analyze the virus and transduction procedures are presented. PMID- 26820878 TI - Gastric volvulus with electrocardiographic changes presenting as an acute coronary syndrome. PMID- 26820879 TI - Erratum to: Is this critically ill patient immunocompromised? PMID- 26820877 TI - Understanding the impact of taste changes in oncology care. AB - PURPOSE: Taste perception is frequently altered in cancer patients. The purpose of this review is to provide an update on advances in understanding of the basic biology and physiology of taste and how taste and flavor may be impacted in cancer and its treatment. METHODS: A succinct review of the literature on the biology and neurology of taste, taste evaluation, and the impact in oncology is provided. RESULTS: Advances have occurred in the study of the gustatory system. Taste and smell are commonly affected during cancer care, and specific chemosensory complaints may persist in large numbers of cancer survivors. Limited study in oncology patients is available despite the significant impact that taste and smell have on oral intake and general physical and social well-being. CONCLUSIONS: Taste and flavor has had limited study in cancer therapy. Impact on taste and flavor can result in changes ranging from elimination of taste to taste distortions that may be associated with taste aversions, nausea, and dietary compromise. New therapeutics and new approaches in oncology may have additional impact upon taste that requires further study. This paper reviews the current understanding of taste function, taste testing, and its potential impact on cancer care, to serve as a guide for directing further research. PMID- 26820880 TI - LiFe: a liver injury score to predict outcome in critically ill patients. AB - PURPOSE: To develop a liver function-related risk prediction tool to identify acute-on-chronic liver failure patients at greatest risk of in-hospital mortality. METHODS: The LiFe (liver, injury, failure, evaluation) score, was constructed based on the opinions of 157 intensivists within the European Society for Intensive Care Medicine. Experts were surveyed and instructed to weigh the diagnostic importance of each feature of a proposed prediction model. We performed a retrospective cohort study of 1916 patients with chronic liver disease admitted to a medical or surgical ICU between 1997, and 2011 in three large hospitals in Boston, USA, and London, UK, with arterial lactate, total bilirubin and INR drawn at ICU admission. The derivation cohort consisted of ICU patients from Brigham and Women's Hospital and Massachusetts General Hospital in Boston (n = 945), and the validation cohort comprised patients from Kings College Hospital, London, admitted to the Liver Intensive Therapy Unit (n = 971). A clinical prediction model was derived and validated based on a logistic regression model describing the risk of in-hospital mortality as a function of the predictors (arterial lactate 0-1.9, >=2.0-3.9, >=4.0-5.9, >=6.0 mg/dL; total bilirubin 0-1.9, >=2.0-3.9, >=4.0-5.9, >=6.0 mg/dL; INR 0-1.9, >=2.0-3.9, >=4.0 5.9, >=6.0) at ICU admission. Performance analysis of the LiFe score against SOFA, CLIF-SOFA, APACHE II and SAPS II was completed in the validation cohort of critically ill cirrhotic patients. RESULTS: The derivation cohort (n = 941) was 53% male with a mean age of 65 years and an in-hospital mortality rate of 30%. The validation cohort (n = 971) was 63% male with mean age of 51 years and an in hospital mortality rate of 52%. The C statistic for the prediction model was 0.74 (95% CI 0.70-0.77) in the derivation cohort and 0.77 (95% CI 0.74-0.80) in the validation cohort. In the validation cohort, in-hospital mortality was 17% in the low-risk group (0 risk score points), 28% in the intermediate-risk group (1-3 points), 47% in the high-risk group (4-8 points), and 77% in the very high-risk group (>8 points). In the validation cohort, the C statistics for SOFA, CLIF SOFA, APACHE II, and SAPS II were 0.80, 0.81, 0.77, and 0.78, respectively. Further, a significant positive correlation exists between LiFe score and acute on-chronic liver failure grade, (r = 0.478, P < 0.001). CONCLUSIONS: Our LiFe score calculated from arterial lactate, total bilirubin and INR at ICU admission is a simple, quick and easily understandable score that may increase clinical utility for risk prediction in ICU patients with acute-on-chronic liver failure. The LiFe score can be used in place of physiological based scores for early risk prediction in patients with chronic liver disease but is not intended to replace CLIF-SOFA as a benchmark for prognostication. PMID- 26820881 TI - Focus on immunocompromised patients. PMID- 26820882 TI - The dose makes the poison. PMID- 26820883 TI - Ultrasound Evaluation of the Combined Effects of Thoracolumbar Fascia Injury and Movement Restriction in a Porcine Model. AB - The persistence of back pain following acute back "sprains" is a serious public health problem with poorly understood pathophysiology. The recent finding that human subjects with chronic low back pain (LBP) have increased thickness and decreased mobility of the thoracolumbar fascia measured with ultrasound suggest that the fasciae of the back may be involved in LBP pathophysiology. This study used a porcine model to test the hypothesis that similar ultrasound findings can be produced experimentally in a porcine model by combining a local injury of fascia with movement restriction using a "hobble" device linking one foot to a chest harness for 8 weeks. Ultrasound measurements of thoracolumbar fascia thickness and shear plane mobility (shear strain) during passive hip flexion were made at the 8 week time point on the non-intervention side (injury and/or hobble). Injury alone caused both an increase in fascia thickness (p = .007) and a decrease in fascia shear strain on the non-injured side (p = .027). Movement restriction alone did not change fascia thickness but did decrease shear strain on the non-hobble side (p = .024). The combination of injury plus movement restriction had additive effects on reducing fascia mobility with a 52% reduction in shear strain compared with controls and a 28% reduction compared to movement restriction alone. These results suggest that a back injury involving fascia, even when healed, can affect the relative mobility of fascia layers away from the injured area, especially when movement is also restricted. PMID- 26820884 TI - The Real-World Routine Use of Caffeine Citrate in Preterm Infants: A European Postauthorization Safety Study. AB - BACKGROUND: Caffeine citrate is the treatment of choice for apnea of prematurity (AOP). Regulatory agencies have requested real-world data on drug utilization and safety, a postauthorization safety study, of a pharmaceutical-grade caffeine citrate, Peyona, to confirm its benefit for preterm infants. OBJECTIVES: To investigate the clinical use, outcomes, and safety profile of this pharmaceutical grade caffeine citrate in the routine treatment of preterm infants with a gestational age (GA) <37 weeks. METHODS: We conducted a multicenter, noninterventional, prospective study in five European countries. Patients eligible for study enrollment were <37-week GA neonates who received treatment with the pharmaceutical-grade caffeine citrate and whose parents had given informed consent. RESULTS: A total of 506 preterm infants were enrolled from 21 institutions. The pharmaceutical-grade caffeine citrate doses were administered intravenously, orally, or via both routes. The main indication of use was AOP treatment (58%) followed by AOP prophylaxis (37%). Median treatment duration was 21 days. The primary cause of study termination was AOP resolution (n = 407; 80%). Hundred and six patients (21%) required supplemental oxygen on day 28; 48 patients (9.5%) had bronchopulmonary dysplasia at 36 weeks' postmenstrual age. Twenty-three adverse drug reactions were observed in 21 neonates (4.2%); the most frequent was tachycardia (2.3%) and only one (seizures) was considered serious. Thirty-one patients (8.1%) had hepatic or renal functional impairment; the side effects were manageable, and these patients also benefitted from treatment. CONCLUSIONS: The use of this caffeine citrate is safe for the management of AOP in a real-world setting. PMID- 26820885 TI - Increased Expression of Phosphorylated Polo-Like Kinase 1 and Histone in Bypass Vein Graft and Coronary Arteries following Angioplasty. AB - Interventional procedures, including percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass surgery (CABG) to re-vascularize occluded coronary arteries, injure the vascular wall and cause endothelial denudation and medial vascular smooth muscle cell (VSMCs) metaplasia. Proliferation of the phenotypically altered SMCs is the key event in the pathogenesis of intimal hyperplasia (IH). Several kinases and phosphatases regulate cell cycle in SMC proliferation. It is our hypothesis that increased expression and activity of polo-like kinase-1 (PLK1) in SMCs, following PTCA and CABG, contributes to greater SMC proliferation in the injured than uninjured blood vessels. Using immunofluorescence (IF), we assessed the expression of PLK1 and phosphorylated-PLK1 (pPLK1) in post-PTCA coronary arteries, and superficial epigastric vein grafts (SEV) and compared it with those in the corresponding uninjured vessels. We also compared the expressions of mitotic marker phospho histone, synthetic-SMC marker, contractile SMC marker, IFN-gamma and phosphorylated STAT-3 in the post-PTCA arteries, SEV-grafts, and the uninjured vessels. Immunostaining demonstrated an increase in the number of cells expressing PLK1 and pPLK1 in the neointima of post PTCA-coronary arteries and SEV grafts compared to their uninjured counterparts. VSMCs in the neointima showed an increased expression of phospho-histone, synthetic and contractile SMC markers, IFN-gamma and phosphorylated STAT-3. However, VSMCs of uninjured coronaries and SEV had no significant expression of the aforementioned proteins. These data suggest that PLK1 might play a critical role in VSMC mitosis in hyperplastic intima of the injured vessels. Thus, novel therapies to inhibit PLK1 could be developed to inhibit the mitogenesis of VSMCs and control neointimal hyperplasia. PMID- 26820886 TI - Unilateral hypoplasia with contralateral hypertrophy of anterior belly of digastric muscle: a case report. AB - Anomalies of the anterior belly of the digastric muscle (DM) are uncommon. We present a case of hypoplasia of the anterior belly of the left DM with hypertrophy of the anterior belly of the contralateral DM. The importance of recognizing this finding is to differentiate hypoplasia of the anterior belly of the DM from denervation atrophy, and not to confuse contralateral hypertrophy with a submental mass or lymphadenopathy. In denervation atrophy of the anterior belly of the DM, associated atrophy of the ipsilateral mylohyoid muscle is present. Hypertrophy of the anterior belly of the contralateral DM can be differentiated from a submental mass or lymphadenopathy by recognizing its isodensity on computed tomography and isointensity on magnetic resonance imaging to other muscles, without abnormal contrast enhancement. PMID- 26820887 TI - Recurrent Moderate Hypoglycemia Suppresses Brain-Derived Neurotrophic Factor Expression in the Prefrontal Cortex and Impairs Sensorimotor Gating in the Posthypoglycemic Period in Young Rats. AB - Recurrent hypoglycemia is common in infants and children. In developing rat models, recurrent moderate hypoglycemia leads to neuronal injury in the medial prefrontal cortex. To understand the effects beyond neuronal injury, 3-week-old male rats were subjected to 5 episodes of moderate hypoglycemia (blood glucose concentration, approx. 30 mg/dl for 90 min) once daily from postnatal day 24 to 28. Neuronal injury was determined using Fluoro-Jade B histochemistry on postnatal day 29. The effects on brain-derived neurotrophic factor (BDNF) and its cognate receptor, tyrosine kinase receptor B (TrkB) expression, which is critical for prefrontal cortex development, were determined on postnatal day 29 and at adulthood. The effects on prefrontal cortex-mediated function were determined by assessing the prepulse inhibition of the acoustic startle reflex on postnatal day 29 and 2 weeks later, and by testing for fear-potentiated startle at adulthood. Recurrent hypoglycemia led to neuronal injury confined primarily to the medial prefrontal cortex. BDNF/TrkB expression in the prefrontal cortex was suppressed on postnatal day 29 and was accompanied by lower prepulse inhibition, suggesting impaired sensorimotor gating. Following the cessation of recurrent hypoglycemia, the prepulse inhibition had recovered at 2 weeks. BDNF/TrkB expression in the prefrontal cortex had normalized and fear-potentiated startle was intact at adulthood. Recurrent moderate hypoglycemia during development has significant adverse effects on the prefrontal cortex in the posthypoglycemic period. PMID- 26820888 TI - Cytomegalovirus Infection Minimally Affects the Frequencies of B-Cell Phenotypes in Peripheral Blood of Younger and Older Adults. AB - BACKGROUND: An accumulation of late-differentiated CD8+ T-cells together with fewer B-cells and seropositivity for cytomegalovirus (CMV) characterises an 'immune risk profile' associated with mortality in elderly people and represents one of the hallmarks of 'immunosenescence'. OBJECTIVES: While differences in memory T-cell phenotypes between young and old people have been intensively studied, and the role of CMV is well-accepted as a driving force in this regard, the impact of CMV on B-cells, if any, has been relatively neglected thus far. METHODS: Here, we avail ourselves of blood samples from participants of the Berlin Aging Study II (BASE-II) to compare peripheral blood B-cell differentiation phenotypes of 140 age- and gender-matched CMV-seronegative or seropositive adults aged between 24 and 85 years using multicolour flow cytometry analysis. RESULTS: We found that the frequencies of naive B-cells within the CD19+ population were not significantly different in younger and older CMV seronegative people. This was also true in CMV-seropositive subjects. The frequencies of late-differentiated B-cells were also not different in CMV negative elderly and young. However, in marked contrast to the T-cell compartment, this was also true for late differentiated B-cells. Within age groups, the most marked differences in the distribution of B-cell phenotypes were between CMV-seronegative and -seropositive subjects, for both genders. CONCLUSION: These results emphasize the importance of including CMV serostatus in the analysis of immune signatures. Because the proportion of the population infected with CMV increases with age, the effect of CMV rather than age could confound analyses seeking age-associated changes to human immunity. PMID- 26820889 TI - Low-Income US Women Under-informed of the Specific Health Benefits of Consuming Beans. AB - BACKGROUND: Bean consumption can reduce chronic disease risk and improve nutrition status. Consumer knowledge of bean health benefits could lead to increased intakes. Low-income women have poorer health and nutrition, but their level of knowledge about bean health benefits is unknown. Beans are a familiar food of reasonable cost in most settings and are cultural staples for Hispanics and other ethnicities. Study objectives were to assess awareness of bean health benefits among low-income women, and to evaluate any differences by acculturation status for Hispanic women in the Southwestern United States. METHODS: A convenience sample of 406 primarily Mexican-origin (70%) low-income women completed a survey on knowledge of bean health benefits and general food behaviors. Principal components analysis of responses identified two summary scale constructs representing "bean health benefits" and "food behaviors." Acculturation level was the main independent variable in chi-square or ANOVA. RESULTS: The survey completion rate was 86% (406/471). Most women agreed or strongly agreed that beans improved nutrition (65%) and were satiating (62%). Over 50% answered 'neutral' to statements that beans could lower LDL cholesterol (52%), control blood glucose (56%) or reduce cancer risk (56%), indicating indifference or possible lack of knowledge about bean health benefits. There were significant differences by acculturation for beliefs that beans aid weight loss and intestinal health. Scores on the bean health benefits scale, but not the food behavior scale, also differed by acculturation. CONCLUSIONS: Limited resource women have a favorable view of the nutrition value of beans, but the majority did not agree or disagreed with statements about bean health benefits. Greater efforts to educate low-income women about bean health benefits may increase consumption and improve nutrition. PMID- 26820891 TI - Use of in-silico assays to characterize the ADMET profile and identify potential therapeutic targets of fusarochromanone, a novel anti-cancer agent. AB - PURPOSE: For 30 years nature has provided a plethora of natural products with potential meaningful anti-cancer activity. Fusarochromanone (FC101a) is a small molecule fungal metabolite exhibiting potent in-vitro growth inhibitory effects and is capable of inducing apoptosis, suppressing angiogenesis and tumorigenesis, and inhibiting endothelial cell growth in multiple cancer cell lines. Despite all we know regarding FC101a, the mechanism of action and molecular target(s) of this compound have remained an enigma. Furthermore, modest in-vivo activity has been documented and requires addressing. METHOD: Early stage pharmacokinetics (PK) assessment is vital to successful drug development. Herein, we aimed to use in silico assays to i) characterize an in-depth ADMET profile of FC101a and ii) to probe for possible therapeutic targets. Two-dimensional SDF files of FC101a and 13 analogs were introduced into ADMET Predictor Version 7.1 that parses the structures in order to calculate molecular descriptors, which are used to estimate ADMET properties. Calculated ADMET values were analyzed and subjected to multiple drug-like indices, delivering a PK profile of each analog. To probe for possible targets, a total of 49 proteins were introduced into SYBYL-X Version 2.0 platform and the deepest binding pocket of each protein was virtually docked with parent compound, FC101a; with the negative control, FC101b; and with the model compound, kynurenine. RESULTS: Each analog showed promising ADMET qualities, although FC101 Oxazole was identified as the most optimized analog. Despite FC101a having a desirable ADME and toxicity profile, areas of concern were identified and must be addressed in-vitro. These include potential mutagenic properties and estrogen receptor toxicity. We provide potential avenues medicinal chemists could use to achieve higher effective permeation, higher blood brain barrier (BBB) penetration, and higher aqueous solubility in FC101a. Molecular docking assays revealed procaspase-8 - cFLIP(L) complex as a potential biological target and led to proposed mechanisms of action by which FC101a facilitates procaspase-8 heterodimerization, thereby increasing proteolytic activity and up regulating extrinsic apoptosis. CONCLUSION: Our data revealed both potential mechanisms of action and a promising ADMET profile of FC101a. These attributes render FC101a a promising lead candidate for development into a low toxic anti cancer agent effective against a broad range of cancers. PMID- 26820890 TI - Permeation thresholds for hydrophilic small biomolecules across microvascular and epithelial barriers are predictable on basis of conserved biophysical properties. AB - PURPOSE: Neutral small hydrophiles are permeable to varying degrees, across the aqueous pores of phospholipid bilayer protein channels, with their potential for permeation into cells being predictable, on the basis of hydrophilicity and size. Here, it is hypothesized that permeation thresholds for small hydrophiles, across capillary zona occludens tight junction and inter-epithelial junction pore complexes are predictable, on the basis of predicted hydrophilicity in context of predicted molecular size and charge distribution, as are those of cations and anions, on the basis of predicted ionization in context of predicted atomic size. METHODS: Small hydrophiles are categorized by charge distribution. 2-dimensional plots of predicted hydrophilic octanol-to-water partition coefficient (HOWPC; unitless) and predicted van der Waals diameter (vdWD; nm) are generated for each category. The predicted HOWPC-to-vdWD ratio (nm (-1) ), and vdWDs for permeable hydrophile at the maximum and minimum HOWPC-to-vdWD, vdWD @ MAXimum HOWPC-to-vdWD and vdWD @ MINimum HOWPC-to-vdWD are determined. For cations and anions, the ionization-to-atomic diameter ratios (CI or AI-to-AD ratios; nm(-1)) are determined. RESULTS: Per sizes of mixed and pure polyneutral hydrophiles, the permeation size maximum for hydrophiles across tight junction pore complexes is >0.69 <= 0.73 nanometers and across inter-epithelial junction pore complexes is >= 0.81 nanometers. For hydrophiles with anionicity or cationicity, the vdWDs @ MAXimum HOWPC-to-vdWD are less than those of mixed and polyneutral hydrophiles across both tight and inter-epithelial junctions, ranges specific to category and junction type. For cations, the permeation threshold across tight junctions is between the CI-to-AD ratio of Na+ (+2.69 nm(-1)) and CH3-Hg+ (+2.36 nm(-1)), with CH3-Hg+ and K+ (+2.20 nm(-1)) being permeable; and for divalent cations, the threshold across inter-epithelial junctions is between the CI-to-AD ratio of Mg2+ (+6.25 nm(-1)) and Ca2+ (+5.08 nm(-1)) , Ca2+ being semi-permeable. For anions, the permeation threshold across tight junctions is between the AI-to-AD ratio of Cl- (-4.91 nm(-1)) and Br- (-4.17 nm(-1)), and the threshold across inter epithelial junctions is between the AI-to-AD ratio of F- (-7.81 nm(-1)) and Cl- ( 4.91 nm(-1)). CONCLUSIONS: In silico modeling reveals that permeation thresholds, of small molecule hydrophiles, cations and anions across junctional pore complexes, are conserved in the physiologic state. PMID- 26820892 TI - Highly conserved regions in Ebola virus RNA dependent RNA polymerase may be act as a universal novel peptide vaccine target: a computational approach. AB - PURPOSE: Ebola virus (EBOV) is such kind of virus which is responsible for 23,825 cases and 9675 deaths worldwide only in 2014 and with an average diseases fatality rate between 25 % and 90 %. Although, medical technology has tried to handle the problems, there is no Food and Drug Administration (FDA)-approved therapeutics or vaccines available for the prevention, post exposure, or treatment of Ebola virus disease (EVD). METHODS: In the present study, we used the immunoinformatics approach to design a potential epitope-based vaccine against the RNA-dependent RNA polymerase-L of EBOV. BioEdit v7.2.3 sequence alignment editor, Jalview v2 and CLC Sequence Viewer v7.0.2 were used for the initial sequence analysis for securing the conservancy from the sequences. Later the Immune Epitope Database and Analysis Resource (IEDB-AR) was used for the identification of T-cell and B-cellepitopes associated with type I and II major histocompatibility complex molecules analysis. Finally, the population coverage analysis was employed. RESULTS: The core epitope "FRYEFTAPF" was found to be the most potential one, with 100 % conservancy among all the strains of EBOV. It also interacted with both type I and II major histocompatibility complex molecules and is considered as nonallergenic in nature. Finally, with impressive cumulative population coverage of 99.87 % for the both MHC-I and MHC-II class throughout the world population was found for the proposed epitope. CONCLUSION: To end, the projected peptide gave us a solid stand to propose for vaccine consideration and that might be experimented for its potency in eliciting immunity through humoral and cell mediated immune responses in vitro and in vivo. PMID- 26820893 TI - Computational modeling to predict the functions and impact of drug transporters. AB - Transport proteins are important mediators of cellular drug influx and efflux and play crucial roles in drug distribution, disposition and clearance. Drug-drug interactions have increasingly been found to occur at the transporter level and, hence, computational tools for studying drug-transporter interactions have gained in interest. In this short review, we present the most important transport proteins for drug influx and efflux. Computational tools for predicting and understanding the substrate and inhibitor interactions with these membrane-bound proteins are discussed. We have primarily focused on ligand-based and structure based modeling, for which the state-of-the-art and future challenges are also discussed. PMID- 26820894 TI - In vitro cytotoxic and in silico activity of piperine isolated from Piper nigrum fruits Linn. AB - BACKGROUND: Piper nigrum [Piperaceae], commonly known as black pepper is used as medicine fairly throughout the greater part of India and as a spice globally. PURPOSE: To isolate piperine and evaluate in vitro cytotoxic [antiproliferative] activity and in silico method. METHODS: Piperine was isolated from the fruits of P.nigrum. Piperine was characterized by UV,IR, (1)H-NMR, (13)C-NMR and Mass spectrum. Standardization of piperine was done also by HPTLC fingerprinting. In vitro cytotoxic activity was done using HeLa cell lines by MTT assay at different concentrations ranging from 20 to 100 MUg/ml in triplicate and in silico docking studies using enzyme EGFR tyrosine kinase. RESULTS: Fingerprinting of isolated piperine were done by HPTLC method. The IC50 value was found to be 61.94 +/- 0.054 MUg/ml in in vitro cytotoxic activity in HeLa Cell lines. Piperine was subjected to molecular docking studies for the inhibition of the enzyme EGFR tyrosine kinase, which is one of the targets for inhibition of cancer cells. It has shown -7.6 kJ mol(-1) binding and 7.06 kJ mol(-1) docking energy with two hydrogen bonds. CONCLUSION: piperine has shown to possess in vitro cytotoxic activity and in silico studies. PMID- 26820895 TI - Molecular docking studies on InhA, MabA and PanK enzymes from Mycobacterium tuberculosis of ellagic acid derivatives from Ludwigia adscendens and Trewia nudiflora. AB - PURPOSE: There is an urgent need to discover and develop new drugs to combat Mycobacterium tuberculosis, the causative agent of tuberculosis (TB) in humans. In recent years, there has been a renewed interest in the discovery of new anti TB agents from natural sources. In the present investigation, molecular docking studies were carried out on two ellagic acid derivatives, namely pteleoellagic acid (1) isolated from Ludwigia adscendens, and 3,3'-di-O-methyl ellagic acid 4-O alpha-rhamnopyranoside (2) isolated from Trewia nudiflora, to investigate their binding to two enzymes involved in M. tuberculosis cell wall biogenesis, namely 2 trans-enoyl-ACP reductase (InhA) and beta-ketoacyl-ACP reductase (MabA), and to pantothenate kinase (PanK type I) involved in the biosynthesis of coenzyme A, essential for the growth of M. tuberculosis. METHODS: Molecular docking experiments were performed using AutoDock Vina. The crystal structures of InhA, MabA and PanK were retrieved from the RCSB Protein Data Bank (PDB). Isonicotinic acyl-NADH for InhA and MabA, and triazole inhibitory compound for PanK, were used as references. RESULTS: Pteleoellagic acid showed a high docking score, estimated binding free energy of -9.4 kcal/mol, for the MabA enzyme comparable to the reference compound isonicotinic-acyl-NADH. CONCLUSIONS: Knowledge on the molecular interactions of ellagic acid derivatives with essential M. tuberculosis targets could prove a useful tool for the design and development of future anti TB drugs. PMID- 26820896 TI - Substantial Increases Occur in Serum Activins and Follistatin during Lung Transplantation. AB - BACKGROUND: Lung transplantation exposes the donated lung to a period of anoxia. Re-establishing the circulation after ischemia stimulates inflammation causing organ damage. Since our published data established that activin A is a key pro inflammatory cytokine, we assessed the roles of activin A and B, and their binding protein, follistatin, in patients undergoing lung transplantation. METHODS: Sera from 46 patients participating in a published study of remote ischemia conditioning in lung transplantation were used. Serum activin A and B, follistatin and 11 other cytokines were measured in samples taken immediately after anaesthesia induction, after remote ischemia conditioning or sham treatment undertaken just prior to allograft reperfusion and during the subsequent 24 hours. RESULTS: Substantial increases in serum activin A, B and follistatin occurred after the baseline sample, taken before anaesthesia induction and peaked immediately after the remote ischemia conditioning/sham treatment. The levels remained elevated 15 minutes after lung transplantation declining thereafter reaching baseline 2 hours post-transplant. Activin B and follistatin concentrations were lower in patients receiving remote ischemia conditioning compared to sham treated patients but the magnitude of the decrease did not correlate with early transplant outcomes. CONCLUSIONS: We propose that the increases in the serum activin A, B and follistatin result from a combination of factors; the acute phase response, the reperfusion response and the use of heparin-based anti-coagulants. PMID- 26820897 TI - Experimental Evolution of Trichoderma citrinoviride for Faster Deconstruction of Cellulose. AB - Engineering faster cellulose deconstruction is difficult because it is a complex, cooperative, multi-enzyme process. Here we use experimental evolution to select for populations of Trichoderma citrinoviride that deconstruct up to five-fold more cellulose. Ten replicate populations of T. citrinoviride were selected for growth on filter paper by serial culture. After 125 periods of growth and transfer to fresh media, the filter paper deconstruction increased an average of 2.5 fold. Two populations were examined in more detail. The activity of the secreted cellulase mixtures increased more than two-fold relative to the ancestor and the largest increase was in the extracellular beta-glucosidase activity. qPCR showed at least 16-fold more transcribed RNA for egl4 (endoglucanase IV gene), cbh1 (cellobiohydrolase I gene) and bgl1 (extracellular beta-glucosidase I gene) in selected populations as compared to the ancestor, and earlier peak expressions of these genes. Deep sequencing shows that the regulatory strategies used to alter cellulase secretion differ in the two strains. The improvements in cellulose deconstruction come from earlier expression of all cellulases and increased relative amount of beta-glucosidase, but with small increases in the total secreted protein and therefore little increase in metabolic cost. PMID- 26820898 TI - Identification and Management of Chronic Pain in Primary Care: a Review. AB - Chronic pain is a common, complex, and challenging condition, where understanding the biological, social, physical and psychological contexts is vital to successful outcomes in primary care. In managing chronic pain the focus is often on promoting rehabilitation and maximizing quality of life rather than achieving cure. Recent screening tools and brief intervention techniques can be effective in helping clinicians identify, stratify and manage both patients already living with chronic pain and those who are at risk of developing chronic pain from acute pain. Frequent assessment and re-assessment are key to ensuring treatment is appropriate and safe, as well as minimizing and addressing side effects. Primary care management should be holistic and evidence-based (where possible) and incorporates both pharmacological and non-pharmacological approaches, including psychology, self-management, physiotherapy, peripheral nervous system stimulation, complementary therapies and comprehensive pain-management programmes. These may either be based wholly in primary care or supported by appropriate specialist referral. PMID- 26820900 TI - Chiral Dihydrobenzofuran Acids Show Potent Retinoid X Receptor-Nuclear Receptor Related 1 Protein Dimer Activation. AB - The nuclear receptor Nurr1 can be activated by RXR via heterodimerization (RXR Nurr1) and is a promising target for treating neurodegenerative diseases. We herein report the enantioselective synthesis and SAR of sterically constricted benzofurans at RXR. The established SAR, using whole cell functional assays, lead to the full agonist 9a at RXR (pEC50 of 8.2) and RXR-Nurr1. The X-ray structure shows enantiomeric discrimination where 9a optimally addresses the ligand binding pocket of RXR. PMID- 26820899 TI - Spontaneous Decoding of the Timing and Content of Human Object Perception from Cortical Surface Recordings Reveals Complementary Information in the Event Related Potential and Broadband Spectral Change. AB - The link between object perception and neural activity in visual cortical areas is a problem of fundamental importance in neuroscience. Here we show that electrical potentials from the ventral temporal cortical surface in humans contain sufficient information for spontaneous and near-instantaneous identification of a subject's perceptual state. Electrocorticographic (ECoG) arrays were placed on the subtemporal cortical surface of seven epilepsy patients. Grayscale images of faces and houses were displayed rapidly in random sequence. We developed a template projection approach to decode the continuous ECoG data stream spontaneously, predicting the occurrence, timing and type of visual stimulus. In this setting, we evaluated the independent and joint use of two well-studied features of brain signals, broadband changes in the frequency power spectrum of the potential and deflections in the raw potential trace (event related potential; ERP). Our ability to predict both the timing of stimulus onset and the type of image was best when we used a combination of both the broadband response and ERP, suggesting that they capture different and complementary aspects of the subject's perceptual state. Specifically, we were able to predict the timing and type of 96% of all stimuli, with less than 5% false positive rate and a ~20ms error in timing. PMID- 26820901 TI - Epithelial cells are a source of natural IgM that contribute to innate immune responses. AB - Currently, natural IgM antibodies are considered to be the constitutively secreted products of B-1 cells in mice and humans. In this study, we found that mouse epithelial cells, including liver epithelial cells and small intestinal epithelial cells (IECs), could express IgM that also showed natural antibody activity. Moreover, similar to the B-1 cell-derived natural IgM that can be upregulated by TLR9 agonists (mimicking bacterial infection), the expression of epithelial cell-derived natural IgM could also be significantly increased by TLR9 signaling. More importantly, the epithelial cell-derived IgM was polyreactive, and it could recognize single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), lipopolysaccharide (LPS), and insulin with low affinity; additionally, TLR9 agonists could enhance it in a MyD88-dependent manner. Furthermore, epithelial cell-derived IgM could bind various bacteria; therefore, it could be involved in anti-infection responses. Together, these results highlight the fact that epithelial cells are an important source of natural IgM, in addition to that produced by B-1 cells, and IgM contributes to the innate immune responses in local tissues, further demonstrating that the epithelium is a first line of defense in the protection against invading microbes. PMID- 26820902 TI - Modelling affective pain in mice: Effects of inflammatory hypersensitivity on place escape/avoidance behaviour, anxiety and hedonic state. AB - BACKGROUND: The place escape/avoidance paradigm (PEAP) has been used to assess the affective component of pain in rats. Using the Complete Freund's Adjuvant (CFA) model of inflammatory pain, the current study aimed at developing a mouse version of PEAP and investigating the relation between PEAP and other behavioural responses, namely anxiety-like behaviour, locomotor activity, and hedonic state. NEW METHOD: A novel paradigm assessing the affective component of pain in mice was developed by modifying the setup known from rat studies: Animals were forced to stay 2 * 5 min in the light and the dark area of a box while being stimulated with a suprathreshold filament on the untreated or treated paw, respectively. This was followed by a 30-min test with unrestricted movement. Anxiety-like behaviour, locomotor activity, and hedonic state were assessed with the elevated zero maze (EZM), an open field setup, and a saccharin preference test, respectively, and correlated with the PEAP behaviour to examine potentially confounding parameters of the novel paradigm. RESULTS: In the PEAP, CFA-treated animals spent more time in the light area. CFA also increased anxiety-like behaviour significantly, whereas locomotor activity was unaffected. A significant, albeit modest, reduction in saccharin preference was observed. PEAP responses showed no significant correlations with any other behavioural measure. COMPARISON WITH EXISTING METHOD AND CONCLUSIONS: The PEAP results suggest that this paradigm might be successfully applied in mice to study affective pain. CFA treatment was associated with increased anxiety-like behaviour and anhedonia; however, this appeared unrelated to the PEAP responses. PMID- 26820903 TI - Microelectrode array stimulation combined with intrinsic optical imaging: A novel tool for functional brain mapping. AB - BACKGROUND: Functional brain mapping via cortical microstimulation is a widely used clinical and experimental tool. However, data are traditionally collected point by point, making the technique very time consuming. Moreover, even in skilled hands, consistent penetration depths are difficult to achieve. Finally, the effects of microstimulation are assessed behaviorally, with no attempt to capture the activity of the local cortical circuits being stimulated. NEW METHOD: We propose a novel method for functional brain mapping, which combines the use of a microelectrode array with intrinsic optical imaging. The precise spacing of electrodes allows for fast, accurate mapping of the area of interest in a regular grid. At the same time, the optical window allows for visualization of local neural connections when stimulation is combined with intrinsic optical imaging. RESULTS: We demonstrate the efficacy of our technique using the primate motor cortex as a sample application, using a combination of microstimulation, imaging and electrophysiological recordings during wakefulness and under anesthesia. Comparison with current method: We find the data collected with our method is consistent with previous data published by others. We believe that our approach enables data to be collected faster and in a more consistent fashion and makes possible a number of studies that would be difficult to carry out with the traditional approach. CONCLUSIONS: Our technique allows for simultaneous modulation and imaging of cortical sensorimotor networks in wakeful subjects over multiple sessions which is highly desirable for both the study of cortical organization and the design of brain machine interfaces. PMID- 26820905 TI - Comparison of bNOS and chat immunohistochemistry in the laterodorsal tegmentum (LDT) and the pedunculopontine tegmentum (PPT) of the mouse from brain slices prepared for electrophysiology. AB - BACKGROUND: Identification of cell phenotype from brain slices upon which in vitro electrophysiological recordings have been performed often relies on conducting post hoc immunohistochemistry on tissue that necessarily has not been ideally prepared for immunohistochemical procedures. In such studies, antibody labeling against neuronal nitric oxide synthase (bNOS) has been used to identify cholinergic neurons of the laterodorsal tegmental nucleus (LDT) and the pedunculopontine tegmental nuclei (PPT), two brainstem nuclei importantly involved in arousal. However, a widespread perception maintains that antibody staining for enzymes involved in synthesis or transport, of acetylcholine would be a more definitive marker and hence, preferable. NEW METHOD: Colocalization of bNOS and CHAT in the LDT/PPT, and presence of parvalbumin (PV), was examined in non-ideally prepared mouse brain slices using currently available antibodies. RESULTS: Using fluorescent-based immunohistochemistry in LDT/PPT slices prepared for in vitro recordings, a near 100% colocalization of bNOS and CHAT was observed. COMPARISON WITH EXISTING METHOD: We confirm in the mouse, findings of near 100% colocalization of bNOS and CHAT in the LDT/PPT, and we expand upon data from rat studies using optimally prepared tissue, that for dendritic visualization, bNOS staining exceeded the quality of CHAT staining for visualization of a higher degree of detail of fine processes. PV is not highly present in the mouse LDT/PPT. CONCLUSION: CHAT and bNOS are equally useful target proteins for immunofluorescent identification of cholinergic LDT/PPT cells in mouse brain slices prepared for in vitro recordings, however, antibody targeting of bNOS allows for a superior appreciation of structural detail. PMID- 26820904 TI - Semi-automated counting of axon regeneration in poly(lactide co-glycolide) spinal cord bridges. AB - BACKGROUND: Spinal cord injury (SCI) is a debilitating event with multiple mechanisms of degeneration leading to life-long paralysis. Biomaterial strategies, including bridges that span the injury and provide a pathway to reconnect severed regions of the spinal cord, can promote partial restoration of motor function following SCI. Axon growth through the bridge is essential to characterizing regeneration, as recovery can occur via other mechanisms such as plasticity. Quantitative analysis of axons by manual counting of histological sections can be slow, which can limit the number of bridge designs evaluated. In this study, we report a semi-automated process to resolve axon numbers in histological sections, which allows for efficient analysis of large data sets. NEW METHOD: Axon numbers were estimated in SCI cross-sections from animals implanted with poly(lactide co-glycolide) (PLG) bridges with multiple channels for guiding axons. Immunofluorescence images of histological sections were filtered using a Hessian-based approach prior to threshold detection to improve the signal-to-noise ratio and filter out background staining associated with PLG polymer. RESULTS: Semi-automated counting successfully recapitulated average axon densities and myelination in a blinded PLG bridge implantation study. COMPARISON WITH EXISTING METHODS: Axon counts obtained with the semi-automated technique correlated well with manual axon counts from blinded independent observers across sections with a wide range of total axons. CONCLUSIONS: This semi-automated detection of Hessian-filtered axons provides an accurate and significantly faster alternative to manual counting of axons for quantitative analysis of regeneration following SCI. PMID- 26820906 TI - Conformational Footprint in Hydrolysis-Induced Nanofibrillation and Crystallization of Poly(lactic acid). AB - The origin of hydrolysis-induced nanofibrillation and crystallization, at the molecular level, was revealed by mapping the conformational ordering during long term hydrolytic degradation of initially amorphous poly(lactic acid) (PLA), a representative model for degradable aliphatic polyesters generally displaying strong interplay between crystallization and hydrolytic erosion. The conformational regularization of chain segments was essentially the main driving force for the morphological evolution of PLA during hydrolytic degradation. For hydrolysis at 37 degrees C, no significant structural variations were observed due to the immobilization of "frozen" PLA chains. In contrast, conformational ordering in PLA was immediately triggered during hydrolysis at 60 degrees C and was responsible for the transition from random coils to disordered trans and, further, to quasi-crystalline nanospheres. On the surfaces, the head-by-head absorption and joining of neighboring nanospheres led to nanofibrillar assemblies following a "gluttonous snake"-like manner. The length and density of nanofibers formed were in close relation to the hydrolytic evolution, both of which showed a direct rise in the initial 60 days and then a gradual decline. In the interior, presumably the high surface energy of the nanospheres allowed for the preferential anchoring and packing of conformationally ordered chains into lamellae. In accordance with the well-established hypothesis, the amorphous regions were attacked prior to the erosion of crystalline entities, causing a rapid increase of crystallinity during the initial 30 days, followed by a gradual fall until 90 days. In addition to adequate illustration of hydrolysis-induced variations of crystallinity, our proposed model elucidates the formation of spherulitic nuclei featuring an extremely wide distribution of diameters ranging from several nanometers to over 5 MUm, as well as the inferior resistance to hydrolysis observed for the primary nuclei. Our work fuels the interest in controlling nanofibrillation mechanism during hydrolysis of PLA, opening up possibilities for straightforward nanofiber formation. PMID- 26820908 TI - Macrocycle Synthesis by Chloride-Templated Amide Bond Formation. AB - A new family of pseudopeptidic macrocyclic compounds has been prepared involving an anion-templated amide bond formation reaction at the macrocyclization step. Chloride anion was found to be the most efficient template in the macrocyclization process, producing improved macrocyclization yields with regard to the nontemplated reaction. The data suggest a kinetic effect of the chloride template, providing an appropriate folded conformation of the open-chain precursor and reducing the energy barrier for the formation of the macrocyclic product. PMID- 26820907 TI - IFNL4 ss469415590 polymorphism contributes to treatment decisions in patients with chronic hepatitis C virus genotype 1b, but not 2a, infection. AB - Recently, the dinucleotide variant ss469415590 (TT/DeltaG) in a novel gene, interferon lambda 4 (IFNL4), was identified as a stronger predictor of hepatitis C virus (HCV) clearance in individuals of African ancestry compared with rs12979860. We aimed to determine whether this variant contributes to treatment decisions in a Chinese population. A total of 447 chronic hepatitis C (CHC) patients (including 328 treated with interferon alpha-2b and ribavirin), 129 individuals who had spontaneously cleared HCV (SHC), and 169 healthy controls were retrospectively investigated. ss469415590 genotyping was performed using a mass spectrometry method (SEQUENOM). A higher proportion of SHC individuals carried the TT/TT genotype compared with CHC patients (95.3% vs. 88.8%, P=0.027). In patients with HCV genotype 1b, the ss469415590 variant was independently associated with sustained virologic response (SVR) (odds ratio [OR]=3.247, 95% confidence interval [CI]=1.038-10.159, P=0.043) and on-treatment virological responses, including rapid (RVR), complete early (cEVR), early (EVR), and end-of treatment (ETVR), with a minimal OR of 3.73. Especially for patients with high viral load (>=4*10(5) IU/ml), DeltaG allele carriers had a lower chance of achieving SVR compared with those carrying the TT/TT genotype (7.1% vs. 36.0%, P=0.034, OR [95% CI]=7.24 [1.02-318.45], negative predictive value=92.9%). In patients with HCV genotype 2a, no significant association between the ss154949590 variant and the virological response was identified (P>0.05). Additionally, we found that ss154949590 was in complete linkage disequilibrium with rs12979860. In conclusion, the IFNL4 ss154949590 TT/TT genotype favors spontaneous clearance of HCV. This same variant is associated with treatment-induced clearance in patients with genotype 1b, but not 2a. ss469415590 (or rs12979860) genotyping should be considered for patients with HCV genotype 1b and high viral load when making a choice between standard dual therapy and an IFN-free direct-acting antiviral regimen. PMID- 26820909 TI - Effects of Crystal Morphology on Singlet Exciton Fission in Diketopyrrolopyrrole Thin Films. AB - Singlet exciton fission (SF) is a promising strategy for increasing photovoltaic efficiency, but in order for SF to be useful in solar cells, it should take place in a chromophore that is air-stable, highly absorptive, solution processable, and inexpensive. Unlike many SF chromophores, diketopyrrolopyrrole (DPP) conforms to these criteria, and here we investigate SF in DPP for the first time. SF yields in thin films of DPP derivatives, which are widely used in organic electronics and photovoltaics, are shown to depend critically on crystal morphology. Time resolved spectroscopy of three DPP derivatives with phenyl (3,6 diphenylpyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione, PhDPP), thienyl (3,6-di(thiophen 2-yl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione, TDPP), and phenylthienyl (3,6-di(5 phenylthiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione, PhTDPP) aromatic substituents in 100-200 nm thin films reveals that efficient SF occurs only in TDPP and PhTDPP (tauSF = 220 +/- 20 ps), despite the fact that SF is most exoergic in PhDPP. This result correlates well with the greater degree of pi overlap and closer pi-stacking in TDPP (3.50 A) and PhTDPP (3.59 A) relative to PhDPP (3.90 A) and demonstrates that SF in DPP is highly sensitive to the electronic coupling between adjacent chromophores. The triplet yield in PhTDPP films is determined to be 210 +/- 35% by the singlet depletion method and 165 +/- 30% by the energy transfer method, showing that SF is nearly quantitative in these films and that DPP derivatives are a promising class of SF chromophores for enhancing photovoltaic performance. PMID- 26820910 TI - Cu(2+) Binds to Phosphatidylethanolamine and Increases Oxidation in Lipid Membranes. AB - Herein, we demonstrate that Cu(2+) binds bivalently to phosphatidylethanolamine (PE), the second most abundant lipid in mammalian cells. The apparent equilibrium dissociation constant, K(DApp), for the Cu(2+)-PE complex at physiological pH is approximately 2 MUM and is insensitive to the concentration of PE in the membrane. By contrast, at pH 10.0, where PE lipids bear a negative charge, K(DApp) decreases with increasing PE content and has a value of 150 nM for bilayers containing 70 mol % PE. The oxidation of double bonds in PE-containing bilayers can be monitored in the presence of Cu(2+). Strikingly, it was found that the oxidation rate is 8.2 times faster at pH 7.4 for bilayers containing 70 mol % PE than for pure phosphatidylcholine (PC) bilayers upon exposure of both to 70 MUM Cu(2+) and 10 mM hydrogen peroxide. The rate of oxidation increases linearly with the PE content in the membrane. These results may help explain the high level of lipid oxidation in PE-containing membranes for neurodegenerative diseases and autism where the Cu(2+) concentration in the body is abnormally high. PMID- 26820912 TI - Evaluation of an intervention designed to improve the management of difficult IUD insertions by advanced practice clinicians. AB - OBJECTIVES: To assess whether clinical skills training in cervical dilation and paracervical anesthesia, as well as the introduction of a clinical protocol for difficult insertions, increased intrauterine device (IUD) insertion success rates among advanced practice clinicians (APCs) including women's health and family practice nurse practitioners, physician assistants and certified nurse midwives. STUDY DESIGN: This prospective study assessed an intervention to improve IUD insertions among APCs at six family planning clinics in Utah. We collected data on IUD insertions performed by participating clinicians during two observation phases: preintervention (Phase 1) and postintervention (Phase 2). Using electronic medical records, we tracked patient characteristics, IUD insertion success, difficulties and failures. We constructed a mixed-effects logistic regression model to control for provider and patient demographics influencing insertion success rates. RESULTS: Nine clinicians participated in both preintervention and postintervention phases. The analysis included 428 IUD insertion procedures (242 preintervention and 186 postintervention). During Phase 1, 31/242 (12.8%) insertions failed. Insertion rates in Phase 2 improved with only 8/186 (4.3%) failures. Using mixed-effects logistic regression, the odds of a successful insertion postintervention was 4.8 times greater than preintervention (aOR=4.8.95% CI 1.8-12.7) when controlling for provider and patient characteristics. Increased risk of insertion failure was associated with nulliparity and younger age during Phase 1, but not during Phase 2. CONCLUSIONS: A brief training for APCs and the use of a clinical protocol for difficult insertions may be able to improve IUD insertion rates. IMPLICATIONS: Clinics with high rates of IUD insertion failure can improve care with a simple intervention, which may yield significant benefits in IUD service delivery. PMID- 26820913 TI - Structural colour printing from a reusable generic nanosubstrate masked for the target image. AB - Structural colour printing has advantages over traditional pigment-based colour printing. However, the high fabrication cost has hindered its applications in printing large-area images because each image requires patterning structural pixels in nanoscale resolution. In this work, we present a novel strategy to print structural colour images from a pixelated substrate which is called a nanosubstrate. The nanosubstrate is fabricated only once using nanofabrication tools and can be reused for printing a large quantity of structural colour images. It contains closely packed arrays of nanostructures from which red, green, blue and infrared structural pixels can be imprinted. To print a target colour image, the nanosubstrate is first covered with a mask layer to block all the structural pixels. The mask layer is subsequently patterned according to the target colour image to make apertures of controllable sizes on top of the wanted primary colour pixels. The masked nanosubstrate is then used as a stamp to imprint the colour image onto a separate substrate surface using nanoimprint lithography. Different visual colours are achieved by properly mixing the red, green and blue primary colours into appropriate ratios controlled by the aperture sizes on the patterned mask layer. Such a strategy significantly reduces the cost and complexity of printing a structural colour image from lengthy nanoscale patterning into high throughput micro-patterning and makes it possible to apply structural colour printing in personalized security features and data storage. In this paper, nanocone array grating pixels were used as the structural pixels and the nanosubstrate contains structures to imprint the nanocone arrays. Laser lithography was implemented to pattern the mask layer with submicron resolution. The optical properties of the nanocone array gratings are studied in detail. Multiple printed structural colour images with embedded covert information are demonstrated. PMID- 26820914 TI - Photo-convertible fluorescent proteins as tools for fresh insights on subcellular interactions in plants. AB - Optical highlighters comprise photo-activatable, photo-switchable and photo convertible fluorescent proteins and are relatively recent additions to the toolbox utilized for live cell imaging research. Here, we provide an overview of four photo-convertible fluorescent proteins (pcFP) that are being used in plant cell research: Eos, Kaede, Maple and Dendra2. Each of these proteins has a significant advantage over other optical highlighters since their green fluorescent nonconverted forms and red fluorescent converted forms are generally clearly visible at expression levels that do not appear to interfere with subcellular dynamics and plant development. These proteins have become increasingly useful for understanding the role of transient and sustained interactions between similar organelles. Tracking of single organelles after green-to-red conversion has provided novel insights on plastids and their stroma filled extensions and on the formation of mega-mitochondria. Similarly colour recovery after photo-conversion has permitted the estimation of nuclear endo reduplication events and is being developed further to image protein trafficking within the lumen of the endoplasmic reticulum. We have also applied photo convertible proteins to create colour-differentiation between similar cell types to follow their development. Both the green and red fluorescent forms of these proteins are compatible with other commonly used single coloured FPs. This has allowed us to develop simultaneous visualization schemes for up to five types of organelles and investigate organelle interactivity. The advantages and caveats associated with the use of photo-convertible fluorescent proteins are discussed. PMID- 26820911 TI - Phenethyl isothiocyanate (PEITC) suppresses prostate cancer cell invasion epigenetically through regulating microRNA-194. AB - SCOPE: Tumor metastasis greatly contributes to the mortality of prostate cancer. The glucosinolate-derived phenethyl isothiocyanate (PEITC) has been widely documented to reduce the risk of prostate cancer by modulating multiple biologically relevant processes. Emerging evidence suggests that PEITC may exert its anti-cancer effects through epigenetic mechanisms including microRNAs. Altered levels of miRNA have been linked to tumor malignancy due to their capacity to regulate functional gene expression in carcinogenesis. Here, we assessed the effects of PEITC on miRNA expression which is related to PCa cell invasiveness. METHODS AND RESULTS: Utilizing oligonucleotide microarray first identified the most affected miRNAs in LNCaP cells after PEITC treatment. Several top altered miRNAs were further validated using quantitative PCR. Interestingly, overexpression of miR-194 suppressed PC3 cell invasion in matrigel-coated Transwell chambers. Bone morphogenetic protein 1 (BMP1) was shown to be a direct target of miR-194. Downregulation of BMP1 by miR-194 or PEITC led to decreased expression of key oncogenic matrix metalloproteinases, MMP2 and MMP9. This in turn resulted in the suppression of tumor invasion. CONCLUSION: Our results indicate that miR-194 downregulates the expression of oncogenic MMP2 and MMP9 by targeting BMP1, which suggests a potential new mechanistic target by which PEITC suppresses prostate cancer cell invasiveness. PMID- 26820915 TI - The Return of Intragastric Balloons for Obesity Management. PMID- 26820916 TI - Endoscopic Measurement of Colorectal Polyps: How Do We Measure Up? PMID- 26820917 TI - Endoscopic Eradication Therapy in Barrett's Esophagus-Related Neoplasia: Setting the Bar Right to Optimize Patient Outcomes. PMID- 26820919 TI - Asymmetric distribution in twin screw granulation. AB - Positron Emission Particle Tracking (PEPT) was successfully employed to validate measured transverse asymmetry in material distribution in the conveying zones of a Twin Screw Granulator (TSG). Flow asymmetry was established to be a property of the granulator geometry and dependent on fill level. The liquid distribution of granules as a function of fill level was determined. High flow asymmetry at low fill level negatively affects granule nucleation leading to high variance in final uniformity. Wetting of material during nucleation was identified as a critical parameter in determining final granule uniformity and fill level is highlighted as a crucial control factor in achieving this. Flow asymmetry of dry material in conveying zones upstream of binder fluid injection leads to poor non uniform wetting at nucleation and results in heterogeneous final product. The granule formation mechanism of 60 degrees F kneading blocks is suggested to be primarily breakage of agglomerates formed during nucleation. Optimisation of screw configuration would be required to provide secondary growth. This work shows how fill dependent flow regimes affect granulation mechanisms. PMID- 26820918 TI - Different faces of Nocardia infection in renal transplant recipients. AB - AIM: Nocardia infections are an uncommon but important cause of morbidity and mortality in renal transplant recipients. The present study was carried out to determine the spectrum of Nocardia infections in a renal transplant centre in Australia. METHODS: A retrospective chart analysis of all renal transplants performed from 2008 to 2014 was conducted to identify cases of culture proven Nocardia infection. The clinical course for each patient with nocardiosis was examined. RESULTS: Four of the 543 renal transplants patients developed Nocardia infection within 2 to 13 months post-transplant. All patients were judged at high immunological risk of rejection pre-transplant and had received multiple sessions of plasmaphoeresis and intravenous immunoglobulin before the onset of the infection. Two patients presented with pulmonary nocardiosis and two with cerebral abscesses. One case of pulmonary nocardiosis was complicated by pulmonary aspergillosis and the other by cytomegalovirus pneumonia. All four patients improved with combination antibiotic therapy guided by drug susceptibility testing. At the time of Nocardia infection all four patients were receiving primary prophylaxis with trimethoprim/sulphamethoxazole (TMP/SMX) 160/800 mg, twice weekly. CONCLUSION: Plasmaphoeresis may be risk factor for Nocardia infection and need further study. Nocardia infection may coexist with other opportunistic infections. Identification of the Nocardia species and drug susceptibility testing is essential in guiding the effective management of patients with Nocardia. Intermittent TMP-SMX (one double strength tablet, twice a week) appears insufficient to prevent Nocardia infection in renal transplant recipients. PMID- 26820920 TI - Mathematical PKPD and safety model of bispecific TfR/BACE1 antibodies for the optimization of antibody uptake in brain. AB - Treatment of diseases of the central nervous system by monoclonal antibodies may be limited by the restricted uptake of antibodies across the blood-brain barrier (BBB). An antibody targeting transferrin receptor (TfR) has been shown to take advantage of the receptor-mediated transcytosis properties of TfR in order to cross the BBB in mice, with the uptake in the brain being dependent on the affinity to TfR. In the bispecific format with arms targeting both TfR and beta secretase 1 (BACE1), altering the affinity to TfR has been shown to impact systemic exposure and safety profiles. In this work, a mathematical model incorporating pharmacokinetic/pharmacodynamic (PKPD) and safety profiles is developed for bispecific TfR/BACE1 antibodies with a range of affinities to TfR in order to guide candidate selection. The model captures the dependence of both systemic and brain exposure on TfR affinity and the subsequent impact on brain Abeta40 lowering and circulating reticulocyte levels. Model simulations identify the optimal affinity for the TfR arm of the bispecific to maximize Abeta reduction while maintaining reticulocyte levels. The model serves as a useful tool to prioritize and optimize preclinical studies and has been used to support the selection of additional candidates for further development. PMID- 26820921 TI - Reutilization of green liquor chemicals for pretreatment of whole rice waste biomass and its application to 2,3-butanediol production. AB - The performance of green liquor pretreatment using Na2CO3 and Na2SO3 and its optimization for whole rice waste biomass (RWB) was investigated. Incubation of Na2CO3-Na2SO3 at a 1:1 ratio (chemical charge 10%) for 12% RWB at 100 degrees C for 6h resulted in maximum delignification (58.2%) with significant glucan yield (88%) and total sugar recovery (545mg/g of RWB) after enzymatic hydrolysis. Recovery and reusability of the resulting chemical spent wash were evaluated to treat RWB along with its compatibility for enzymatic digestibility. Significant hydrolysis and lignin removal were observed for up to three cycles; however, further reuse of Na2CO3 and Na2SO3 lowered their performance. Significant 2,3 butanediol (BDO) was produced by Klebsiella pneumoniae KMK-05 with the RWB enzymatic hydrolysate from each pretreatment cycle. BDO yield achieved using RWB derived sugars was similar to those using laboratory-grade sugars. This pretreatment strategy constitutes an ecofriendly, cost-effective, and practical method for utilizing lignocellulosic biomass. PMID- 26820922 TI - Effect of harvest date on Arundo donax L. (giant reed) composition, ensilage performance, and enzymatic digestibility. AB - Composition and ensilage performance of giant reed harvested in August, October, November, and December, were evaluated and compared. Generally, late-harvested giant reed had higher dry matter content, lower nitrogen content, and higher water soluble carbohydrates (WSC) content than early-harvested giant reed. During 90days of ensilage, giant reed harvested in October, November, and December showed dry matter losses of about 1%, while giant reed harvested in August showed a higher dry matter loss of about 8%. During the ensilage process, more lactic acid was produced in late-harvested giant reed than in early-harvested giant reed. Late-harvested giant reed had a higher lignin content and lower enzymatic digestibility than early-harvested giant reed. However, enzymatic digestibility of all the giant reed biomass was improved by the 90-day ensilage process, reaching levels of 43-46%. In summary, ensilage could be used for storing giant reed biomass harvested at different times and for improving its digestibility. PMID- 26820923 TI - Electricity generation from food wastes and characteristics of organic matters in microbial fuel cell. AB - The microbial fuel cell (MFC) was evaluated as an alternative way to recover electricity from canteen based food waste. Characteristics of the organics in food waste before and after the MFC treatment were analyzed to investigate how the organic matters were biodegraded and transformed during the MFC treatment. A maximum power density of 5.6W/m(3) and an average output voltage of 0.51V were obtained. During the MFC operation, the hydrophilic and acidic fractions were more readily degraded, compared to the neutral fractions. Additionally, aromatic compounds in the hydrophilic fraction were more preferentially removed than non aromatic compounds. The MFC could easily remove the tryptophan protein-like substances in all fractions and aromatic proteins in hydrophilic and hydrophobic neutral fractions. Additionally, the hydrophobic amide-1 proteins and aliphatic components were readily hydrolyzed and biodegraded in the MFC. These findings may facilitate the pretreatment and posttreatment choices for MFC system fed with food waste. PMID- 26820924 TI - A comparative study on flocculating ability and growth potential of two microalgae in simulated secondary effluent. AB - The flocculating ability was an important property to microalgal harvesting, especially in secondary effluent. In this study, the flocculating ability of two microalgae, Chlorococcum sp. GD and Parachlorella kessleri TY, was evaluated after 10d of cultivation in secondary effluent. After 180min of settling, the flocculating ability of Chlorococcum sp. GD and P. kessleri TY was 84.43% and 16.23%, respectively. It was suggested that Chlorococcum sp. GD was an excellent self-flocculating microalgae. The mechanism on self-flocculating of Chlorococcum sp. GD was probably related to hydrophobic extracellular polymeric substances (EPS). Besides, compared to P. kessleri TY, the nitrogen and phosphorus removal efficiency of Chlorococcum sp. GD was high, which was up to 66.51% and 74.19%, respectively. Chlorococcum sp. GD also had high lipid content and biomass concentration. Therefore, Chlorococcum sp. GD could be regarded as a promising candidate for microalgal cultivation and harvesting in secondary effluent. PMID- 26820925 TI - Production of hydrogen, ethanol and volatile fatty acids through co-fermentation of macro- and micro-algae. AB - Algae may be fermented to produce hydrogen. However micro-algae (such as Arthrospira platensis) are rich in proteins and have a low carbon/nitrogen (C/N) ratio, which is not ideal for hydrogen fermentation. Co-fermentation with macro algae (such as Laminaria digitata), which are rich in carbohydrates with a high (C/N) ratio, improves the performance of hydrogen production. Algal biomass, pre treated with 2.5% dilute H2SO4 at 135 degrees C for 15min, effected a total yield of carbohydrate monomers (CMs) of 0.268g/g volatile solids (VS). The CMs were dominating by glucose and mannitol and most (ca. 95%) were consumed by anaerobic fermentative micro-organisms during subsequent fermentation. An optimal specific hydrogen yield (SHY) of 85.0mL/g VS was obtained at an algal C/N ratio of 26.2 and an algal concentration of 20g VS/L. The overall energy conversion efficiency increased from 31.3% to 54.5% with decreasing algal concentration from 40 to 5 VS g/L. PMID- 26820926 TI - Current implications of past DDT indoor spraying in Oman. AB - In Oman, DDT was sprayed indoors during an intensive malaria eradication program between 1976 and 1992. DDT can remain for years after spraying and is associated with potential health risk. This raises the concern for human exposure in areas where DDT was used for indoor spraying. Twelve houses in three regions with a different history of DDT indoor spraying were chosen for a sampling campaign in 2005 to determine p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), p,p' dichlorodiphenyldichloroethylene (p,p'-DDE) and p,p' dichlorodiphenyldichloroethane (p,p'-DDD) levels in indoor air, dust, and outdoor soil. Although DDT was only sprayed indoor, p,p'-DDT, p,p'-DDE and p,p'-DDD were also found in outdoor soil. The results indicate that release and exposure continue for years after cessation of spraying. The predicted cancer risk based on concentrations determined in 2005, indicate that there was still a significant cancer risk up to 13 to 16years after indoor DDT spraying. A novel approach, based on region-specific half-lives, was used to predict concentrations in 2015 and showed that more than 21years after spraying, cancer risk for exposure to indoor air, dust, and outdoor soil are acceptable in Oman for adults and young children. The model can be used for other locations and countries to predict prospective exposure of contaminants based on indoor experimental measurements and knowledge about the spraying time-schedule to extrapolate region-specific half-lives and predict effects on the human population years after spraying. PMID- 26820927 TI - Oxidative acid treatment and characterization of new biocarbon from sustainable Miscanthus biomass. AB - Oxidative acid treatments of biochar produced from Miscanthus were performed in this study using nitric acid, sulfuric acid, and a mixture of both. The structural and morphological changes of the acid-treated biochar were investigated using Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), Raman spectroscopy, organic elemental analysis and energy-dispersive X-ray spectroscopy (EDS). Improved surface functionality of the treated biochars was observed in their respective FT-IR spectra through the presence of nitro and carboxylic acid functional groups. SEM-EDS and elemental analysis revealed a large increase in the oxygen to carbon ratio in the biochar, which was evidence of chemical oxidation from the acid treatment. Further, TGA study showed the reduced thermal stability of acid-treated biochar over 200 degrees C due to the increased oxygen content. Acid treatments also influenced the graphitic structure of the biochar, as observed in the Raman spectra. The results suggest that biochar can be successfully functionalized for composite applications and provide a sustainable alternative to petroleum-based carbon additives. PMID- 26820928 TI - Inverse association of highly chlorinated dioxin congeners in maternal breast milk with dehydroepiandrosterone levels in three-year-old Vietnamese children. AB - This study aims to evaluate the endocrine-disrupting effect of dioxin congeners on adrenal steroid hormones in mother-child pairs. In our previous study, we found that cortisol and cortisone levels were higher in the blood and the saliva of mothers living in a dioxin hotspot area than in mothers from a non-exposed region in Vietnam. In this follow-up study, we determined the salivary steroid hormone levels in 49 and 55 three-year-old children of these mothers in the hotspot and non-exposed region, respectively. Steroid hormones were determined by liquid chromatography-tandem mass spectrometry, and dioxin in the maternal breast milk was determined by gas chromatography-mass spectrometry. Dioxin levels in the breast milk of mothers from the hotspot (median total toxic equivalents polychlorinated dibenzodioxins/polychlorinated dibenzofurans; (TEQ PCDD/Fs) of 11pg/g lipid) were three to four times higher than those of mothers in the non exposed region (median TEQ PCDD/Fs of 3.07pg/g lipid). Salivary dehydroepiandrosterone (DHEA) levels in children were found to be significantly lower in the hotspot than in the non-exposed region, while cortisol and cortisone levels were not different between the two regions. Highly chlorinated dioxin congeners, such as octacholorodibenzodioxin (OCDD), 1,2,3,4,6,7,8 heptacholorodibenzodioxin (HpCDD) and 1,2,3,4 (or 6), 7,8-hexachlorodibenzodioxin Hx(CDD), showed stronger inverse associations with the children's salivary DHEA than other lowly chlorinated dioxin congeners. Glucocorticoid levels in the mothers exhibited a significantly positive correlation with OCDD and HpCDD/F (polychlorinated dibenzofurans). In conclusion, highly chlorinated dioxin congeners are more strongly correlated with endocrine-disrupting effects on adrenal hormones, resulting in high cortisol levels in the mothers and low DHEA levels in their three-year-old children. PMID- 26820930 TI - Untreated runoff quality from roof and road surfaces in a low intensity rainfall climate. AB - Sediment and heavy metals in stormwater runoff are key pollutants of urban waterways, and their presence in stormwater is driven by climatic factors such as rainfall intensity. This study describes the total suspended solids (TSS) and heavy metal concentrations found in runoff from four different urban surfaces within a residential/institutional catchment, in a climate where rainfall is typically of low intensity (<5.1mm.h(-1)). The results were compared to untreated runoff quality from a compilation of international studies. The road runoff had the highest TSS concentrations, while copper and galvanized roof runoff had the highest copper and zinc concentrations, respectively. Pollutant concentrations were found to be significantly different between surfaces; quantification and prediction of pollutant contributions from urban surfaces should thus take account of the different surface materials, instead of being aggregated into more generalized categories such as land use. The TSS and heavy metal concentrations were found to be at the low to medium end of ranges observed internationally, except for total copper and zinc concentrations generated by dissolution of copper and galvanized roofing material respectively; these concentrations were at least as high as those reported internationally. TSS wash-off from the roofs was seen to be a source-limited process, where all available TSS is washed off during the rain event despite the low intensity rainfall, whereas both road TSS and heavy metals wash-off from roof and road surfaces appeared to all be transport limited and therefore some carryover of pollutants occurs between rain events. A first flush effect was seen from most surfaces for TSS, but not for heavy metals. This study demonstrates that in low intensity rainfall climates, quantification of untreated runoff quality from key individual surface types in a catchment are needed to enable development of targeted and appropriately sized stormwater treatment systems. PMID- 26820929 TI - Coordinated management of combined sewer overflows by means of environmental decision support systems. AB - During heavy rainfall, the capacity of sewer systems and wastewater treatment plants may be surcharged producing uncontrolled wastewater discharges and a depletion of the environmental quality. Therefore there is a need of advanced management tools to tackle with these complex problems. In this paper an environmental decision support system (EDSS), based on the integration of mathematical modeling and knowledge-based systems, has been developed for the coordinated management of urban wastewater systems (UWS) to control and minimize uncontrolled wastewater spills. Effectiveness of the EDSS has been tested in a specially designed virtual UWS, including two sewers systems, two WWTP and one river subjected to typical Mediterranean rain conditions. Results show that sewer systems, retention tanks and wastewater treatment plants improve their performance under wet weather conditions and that EDSS can be very effective tools to improve the management and prevent the system from possible uncontrolled wastewater discharges. PMID- 26820931 TI - Critical role of meteorological conditions in a persistent haze episode in the Guanzhong basin, China. AB - In the present study, the critical role of the meteorological condition in a persistent extreme haze episode that occurred in Guanzhong basin of China on December 16 to 25, 2013 has been investigated. Analyses of the large-scale meteorological conditions on 850hPa during the episode have been performed using the NCEP FNL data set, indicating that synoptic situations generally facilitate the accumulation of pollutants either in horizontal or vertical directions in the basin. The FLEXPART model has been utilized to illustrate the pollutant transport patterns during the episode, further showing the dominant role of synoptic conditions in accumulation of pollutants in the basin. Detailed meteorological conditions, such as temperature inversion, and low-level horizontal wind speed also contribute to the extreme haze episode. In addition, the WRF-CHEM model has been used to evaluate the responses of the surface PM2.5 level to the emission mitigation. Generally, the predicted PM2.5 spatial patterns and temporal variations agree well with the observations at the ambient monitoring sites. Sensitivity studies show that the emissions in the basin need to be mitigated by more than 91% to meet the excellent level of the China National Air Quality Standard under the extremely unfavorable meteorological conditions, demonstrating that it is imperative to implement stringent controls on emissions to improve the air quality. PMID- 26820932 TI - Study of particulate matter from Primary/Secondary Marine Aerosol and anthropogenic sources collected by a self-made passive sampler for the evaluation of the dry deposition impact on built heritage. AB - Dry deposition is one of the most dangerous processes that can take place in the environment where the compounds that are suspended in the atmosphere can react directly on different surrounding materials, promoting decay processes. Usually this process is related with industrial/urban fog and/or marine aerosol in the coastal areas. Particularly, marine aerosol transports different types of salts which can be deposited on building materials and by dry deposition promotes different decay pathways. A new analytical methodology based on the combined use of Raman Spectroscopy and SEM-EDS (point-by-point and imaging) was applied. For that purpose, firstly evaporated seawater (presence of Primary Marine Aerosol (PMA)) was analyzed. After that, using a self-made passive sampler (SMPS), different suspended particles coming from marine aerosol (transformed particles in the atmosphere (Secondary Marine Aerosol (SMA)) and metallic airborne particulate matter coming from anthropogenic sources, were analyzed. Finally in order to observe if SMA and metallic particles identified in the SMPS can be deposited on a building, sandstone samples from La Galea Fortress (Getxo, north of Spain) located in front of the sea and in the place where the passive sampler was mounted were analyzed. PMID- 26820933 TI - Profiling microbial community in a watershed heavily contaminated by an active antimony (Sb) mine in Southwest China. AB - Located in Southwest China, the Chahe watershed has been severely contaminated by upstream active antimony (Sb) mines. The extremely high concentrations of Sb make the Chahe watershed an excellent model to elucidate the response of indigenous microbial activities within a severe Sb-contaminated environment. In this study, water and surface sediments from six locations in the Chahe watershed with different levels of Sb contamination were analyzed. Illumina sequencing of 16S rRNA amplicons revealed more than 40 phyla from the domain Bacteria and 2 phyla from the domain Archaea. Sequences assigned to the genera Flavobacterium, Sulfuricurvum, Halomonas, Shewanella, Lactobacillus, Acinetobacter, and Geobacter demonstrated high relative abundances in all sequencing libraries. Spearman's rank correlations indicated that a number of microbial phylotypes were positively correlated with different speciation of Sb, suggesting potential roles of these phylotypes in microbial Sb cycling. Canonical correspondence analysis further demonstrated that geochemical parameters, including water temperature, pH, total Fe, sulfate, aqueous Sb, and Eh, significantly structured the overall microbial community in Chahe watershed samples. Our findings offer a direct and reliable reference to the diversity of microbial communities in the presence of extremely high Sb concentrations, and may have potential implications for in situ bioremediation strategies of Sb contaminated sites. PMID- 26820934 TI - Airborne iron across major urban centers in South Korea between 1991 and 2012. AB - In this study, the distribution of airborne iron (Fe), one of the most abundant heavy metals in the Earth's crust was investigated to describe the basic features of i'ts pollution in various urban locations. The spatiotemporal distribution of Fe concentrations in seven major South Korean cities exhibited unique patterns to reflect differences as to Fe sources reflected in the relative enrichment in coastal relative to inland areas. In addition, the analysis of long-term trends of different metal species indicated that Fe levels maintained a fairly constant trend, while there had been a noticeable decline in concentrations of other metals (Cd, Cr, Cu, Mn, and Ni). The relative robustness of our correlation analysis was assessed by comparing (1) the Fe concentrations among cities, and (2) Fe with other metals at a given city. Fe concentrations were also partly explainable by the frequency of Asian dust events in most cities, with the observed spatial gradients in such relationships. PMID- 26820936 TI - Understanding the role of soil erosion on co2-c loss using (13)c isotopic signatures in abandoned Mediterranean agricultural land. AB - Understanding soil water erosion processes is essential to evaluate the redistribution of soil organic carbon (SOC) within a landscape and is fundamental to assess the role of soil erosion in the global carbon (C) budget. The main aim of this study was to estimate the C redistribution and losses using (13)C natural abundance. Carbon losses in soil sediment, dissolved organic carbon (DOC) and CO2 emission were determined. Four bounded parallel plots were installed on a 10% slope. In the upper part of the plots, C3soil was replaced with C4soil. The SOC and delta(13)C were measured after 145.2mm rainfall in the upper (2m far from C4strip), middle (4m far from C4strip) lower (6m far from C4strip) trams of the plot and in the sediments collected in the Gerlach collector at the lower part of the plot. A laboratory incubation experiment was performed to evaluate the CO2 emission rate of soils in each area. OC was mainly lost in the sediments as 2.08g(-)(2) of C was lost after 145.2mm rainfall. DOC losses were only 5.61% of off-site OC loss. Three months after the beginning of the experiment, 15.90% of SOC in the upper tram of the plot had a C4 origin. The C4-SOC content decreased along the 6m length of the plot, and in the sediments collected by the Gerlach collector. CO2 emission rate was high in the upper plot tram due to the high SOC content. The discrimination of CO2 in C3 and C4 portion permitted to increase our level of understanding on the stability of SOC and its resilience to decomposition. The transport of sediments along the plot increased SOC mineralization by 43%. Our study underlined the impact of rainfall in C losses in soil and water in abandoned Mediterranean agriculture fields and the consequent implications on the C balance. PMID- 26820935 TI - Quantification of inorganic arsenic exposure and cancer risk via consumption of vegetables in southern selected districts of Pakistan. AB - Human exposures to arsenic (As) through different pathways (dietary and non dietary) are considered to be one of the primary worldwide environmental health risks to humans. This study was conducted to investigate the presence of As in soil and vegetable samples collected from agricultural lands located in selected southern districts of Khyber Pakhtunkhwa (KPK) Province, Pakistan. We examined the concentrations of total arsenic (TAs), organic species of As such as monomethylarsonic acid (MMA) and dimethylarsonic acid (DMA), and inorganic species including arsenite (AsIII) and arsenate (AsV) in both soil and vegetables. The data were used to determine several parameters to evaluate human health risk, including bioconcentration factor (BCF) from soil to plant, average daily intake (ADI), health risk index (HRI), incremental lifetime cancer risk (ILTCR), and hazard quotient (HQ). The total As concentration in soil samples of the five districts ranged from 3.0-3.9mgkg(-1), exhibiting minimal variations from site to site. The mean As concentration in edible portions of vegetable samples ranged from 0.03-1.38mgkg(-1). It was observed that As concentrations in 75% of the vegetable samples exceeded the safe maximum allowable limit (0.1mgkg( 1)) set by WHO/FAO. The highest value of ADI for As was measured for Momordica charantia, while the lowest was for Allium chinense. The results of this study revealed minimal health risk (HI<1) associated with consumption of vegetables for the local inhabitants. The ILTCR values for inorganic As indicated a minimal potential cancer risk through ingestion of vegetables. In addition, the HQ values for total As were <1, indicating minimal non-cancer risk. PMID- 26820937 TI - Distribution of cytokine gene polymorphisms in six Orang Asli subgroups in Peninsular Malaysia. AB - Cytokines are involved in immune responses and the pathogenesis of various diseases. Allelic variations within the genes coding for various ~30 kDa cytokine protein/glycoproteins have been reported for many populations and have been the subjects of many ancestry and health analyses. In this study, we typed 22 single nucleotide polymorphisms (SNPs) in 13 cytokine genes of 165 Orang Asli individuals by using sequence specific primer-polymerase chain reaction (SSP-PCR) assay. The volunteers came from all across the Peninsular of Malaysia and belong to six Orang Asli subgroups; Batek, Kensiu, Lanoh, Che Wong, Semai and Orang Kanaq. Here we report our general findings and original genotype data and their associated analyses (Hardy-Weinberg proportions, estimation of allele and haplotype frequencies) can be found in the supplementary files and will be held at Allele Frequency Net Database (AFND). PMID- 26820939 TI - Correction: Micronutrients in HIV: A Bayesian Meta-Analysis. AB - [This corrects the article DOI: 10.1371/journal.pone.0120113.]. PMID- 26820938 TI - Pin1 modulates chemo-resistance by up-regulating FoxM1 and the involvements of Wnt/beta-catenin signaling pathway in cervical cancer. AB - The prolyl isomerase Pin1, which is frequently highly expressed in many different cancers, can directly regulate cell proliferation and the cell cycle. However, the role of Pin1 in chemo-resistance remains to be elucidated in cervical cancer. The purpose of the present study was to investigate the role of Pin1 in the chemo resistance of cervical cancer. The cisplatin resistance was assessed using the MTT assay. Pin1, FoxM1, beta-catenin, Cyclin D1, and c-myc expression levels were detected by RT-qPCR or Western blot. The results showed that Pin1 expression displayed a similar expression pattern with the resistance to cisplatin in five cervical cell lines. Knockdown of Pin1 significantly increased the sensitivity to cisplatin in HeLa cells, while Pin1 overexpression decreased the sensitivity to cisplatin in Me180 cells. Knockdown of Pin1 significantly down-regulated FoxM1 expression in HeLa cells, while Pin1 overexpression showed a contrary effect in Me180 cells. Besides, overexpression of Pin1 markedly increased the protein expression of beta-catenin and its target genes cyclin D1 and c-myc. FoxM1 siRNA remarkably reversed the promotory effect of pcDNA-Pin1(+) on beta-catenin and its target genes cyclin D1 and c-myc in Me180 cells. Furthermore, we also found that FoxM1 siRNA and IWP-2 markedly decreased cell viability, and IWP-2 decreased cell viability to the maximum extent in the Me180 cells co-transfected with pcDNA Pin1(+) and FoxM1 siRNA. Taken together, these data suggest that Pin1 contributes to cisplatin resistance, partly by up-regulating FoxM1 and Wnt/beta-catenin signaling pathway involved in cervical cancer. PMID- 26820941 TI - Basic Histopathological Methods and Breast Lesion Types for Research. AB - The in situ observation on the tissues, such as histopathology, immunohistochemistry (IHC), immunofluorescence (IF), and in situ hybridization (ISH), is one of the most important methods in the biomedical scientific research. In this chapter we introduce the most often used methods-hematoxylin and eosin (H&E) and double IF staining. H&E staining is used for general morphology by which the different pathological types of breast lesions are identified. The double IF staining is often used to study the protein-protein interaction on tissues for signaling mechanisms. This chapter also includes the histopathology of primary or simplified breast lesion types that is essential for applying the above methods and the reclassification of breast cancers by molecular markers. PMID- 26820940 TI - Naturally-occurring TGR5 agonists modulating glucagon-like peptide-1 biosynthesis and secretion. AB - Selective GLP-1 secretagogues represent a novel potential therapy for type 2 diabetes mellitus. This study examined the GLP-1 secretory activity of the ethnomedicinal plant, Fagonia cretica, which is postulated to possess anti diabetic activity. After extraction and fractionation extracts and purified compounds were tested for GLP-1 and GIP secretory activity in pGIP/neo STC-1 cells. Intracellular levels of incretin hormones and their gene expression were also determined. Crude F. cretica extracts stimulated both GLP-1 and GIP secretion, increased cellular hormone content, and upregulated gene expression of proglucagon, GIP and prohormone convertase. However, ethyl acetate partitioning significantly enriched GLP-1 secretory activity and this fraction underwent bioactivity-guided fractionation. Three isolated compounds were potent and selective GLP-1 secretagogues: quinovic acid (QA) and two QA derivatives, QA 3beta-O-beta-D-glycopyranoside and QA-3beta-O-beta-D-glucopyranosyl-(28->1)-beta D-glucopyranosyl ester. All QA compounds activated the TGR5 receptor and increased intracellular incretin levels and gene expression. QA derivatives were more potent GLP-1 secretagogues than QA. This is the first time that QA and its naturally-occurring derivatives have been shown to activate TGR5 and stimulate GLP-1 secretion. These data provide a plausible mechanism for the ethnomedicinal use of F. cretica and may assist in the ongoing development of selective GLP-1 agonists. PMID- 26820942 TI - Clinical Applications for Immunohistochemistry of Breast Lesions. AB - Immunohistochemical analysis has been a key clinical tool that shows the protein expression of molecular markers. Expression of molecular markers in breast pathology has been used to distinguish breast cancers from benign lesions, classify subtypes of breast cancers, and determine therapeutic intervention. It is a relatively fast and efficient option in stratifying breast lesions to assist in both determining pathology diagnosis and offer strategies to the best course of clinical action. In this chapter, we discuss the use of immunohistochemistry testing for some of the key molecular markers involved in breast pathology that are crucial for classifying breast cancers and the guidelines for the interpretation of testing results that assist in clinical management. PMID- 26820943 TI - Immunohistochemistry for Triple-Negative Breast Cancer. AB - Triple-negative breast cancers are a heterogeneous group of tumors that are, as yet, not entirely understood. Although triple-negative carcinomas are strictly defined as invasive carcinomas lacking expression of estrogen receptor, progesterone receptor, and HER2, some use the terms triple-negative and basal like cancer synonymously. It should be noted that these are not entirely equivalent. Nevertheless, it has been shown that a panel of immunohistochemical markers can be used as a surrogate for genomic profiling and thus to identify basal-like breast cancers. We describe the panels of immunohistochemical markers that can be applied and how to interpret these markers herein. PMID- 26820944 TI - In Situ Hybridization of Breast Cancer Markers. AB - In situ hybridization is an important technique in breast cancer research, which is widely applied in detection of specific nucleic acid sequences. Here, we describe the detailed protocol of fluorescence in situ hybridization and chromogenic in situ hybridization in detection of gene HER2/neu amplification in breast cancer tissues. PMID- 26820945 TI - Evaluation of Human Epidermal Growth Factor Receptor 2 (HER2) Gene Status in Human Breast Cancer Formalin-Fixed Paraffin-Embedded (FFPE) Tissue Specimens by Fluorescence In Situ Hybridization (FISH). AB - Current standard of care requires that HER2 gene testing be performed on all newly diagnosed invasive breast cancers in order to determine eligibility for anti-HER2 antibody therapy and should be performed in accordance with current ASCO-CAP guidelines (Hammond et al., J Clin Oncol 29(15):e458, 2011; Wolff et al., J Clin Oncol 31(31):3997-4013, 2013). Here we describe a HER2 FISH methodology to evaluate HER2 gene status in FFPE breast tumor specimens. PMID- 26820946 TI - Quantification of mRNA Levels Using Real-Time Polymerase Chain Reaction (PCR). AB - Real-time quantitative reverse transcription PCR technique has advanced greatly over the past 20 years. Messenger RNA (mRNA) levels in cells or tissues can be quantified by this approach. It is well known that changes in mRNA expression in disease, and correlation of mRNA expression profiles with clinical parameters, serve as clinically relevant biomarkers. Hence, accurate determination of the mRNA levels is critically important in describing the biological, pathological, and clinical roles of genes in health and disease. This chapter describes a real time PCR approach to detect and quantify mRNA expression levels, which can be used for both laboratorial and clinical studies in breast cancer research. PMID- 26820947 TI - Detection of miRNA in Cultured Cells or Xenograft Tissues of Breast Cancer. AB - MicroRNA (miRNA) analysis has evolved over the past two decades to become a highly specialized field with broad-reaching applications across a multitude of diseases and cellular processes. The choice of an applicable approach for miRNA quantification will depend on a variety of factors such as cost, time constraints, and throughput. Here, we describe the methods of total RNA isolation, AGO2-bound RNA isolation, miRNA polyadenylation, miRNA-cDNA synthesis, and quantitative real-time polymerase chain reaction for the detection of known miRNAs in cultured cells or xenograft tissues of breast cancer. PMID- 26820948 TI - Pyrosequencing Analysis for Breast Cancer DNA Methylome. AB - Unraveling DNA methylation profile of tumor is important for the diagnosis and treatment of cancer patients. Because of the heterogeneity of clinical samples, it is very difficult to get methylation profile of only tumor cells. Laser capture Microdissection (LCM) is giving us a chance to isolate the DNA only from the tumor cells without any stroma cell's DNA contamination. Once we capture the breast tumor cells, we can isolate the genomic DNA which is followed by the bisulfite treatment in which unmethylated cytosines of the CG pairs are converted into uracil; however, methylated cytosine does not go into any chemical change during this reaction. Next, bisulfite treated DNA is used in the regular PCR reaction to get a single band PCR amplicon which will be used as a template for the pyrosequencing. Pyrosequencing is a powerful method to make a quantitative methylation analysis for each specific CG pair. PMID- 26820949 TI - Vita-AssayTM Method of Enrichment and Identification of Circulating Cancer Cells/Circulating Tumor Cells (CTCs). AB - The ability to capture, enrich, and propagate circulating cancer cells/circulating tumor cells (CTCs) for downstream analyses such as ex vivo drug sensitivity testing of short-term cultures of CTCs, single cell sorting of CTCs by fluorescence activated cell sorting (FACS), animal injection tumor and/or metastasis formation studies, next generation sequencing (NGS), gene expression profiling, gene copy number determination, and epigenomic analyses is of high priority and of immense importance to both the basic research and translational/clinical research communities. Vitatex Inc.'s functional cell separation technology, constructed as Vita-AssayTM (AG6W, AN6W, AR6W) culture plates, is based on the preferential adhesion of invasive rare blood cells of tissue origin to a tissue or tumor microenvironment mimic-the so-called cell adhesion matrix (CAM), which has a demonstrated ability to enrich viable CTCs from blood up to one-million fold.The CAM-scaffold allows for the functional capture and identification of invasive CTCs (iCTCs) including invasive tumor progenitor (TP) cells from cancer-patients' blood. CAM-captured CTCs are capable of ingesting the CAM (CAM+) itself. Green and red fluorescent versions of Vita AssayTM (AG6W and AR6W) allow for direct visualization of CAM-uptake by cancer cells. Vita-AssayTM CAM-enrichment has allowed for sensitive multiplex flow cytometric and microscopic detection of iCTCs from patients with cancers of the breast, ovary, prostate, pancreas, colorectum, and lung; it has also been successfully utilized for ex vivo drug-sensitivity testing of ovarian-cancer patient CTCs. The CAM enrichment method is equally suitable for the separation of iCTCs and TP cells in ascites and pleural fluid. PMID- 26820950 TI - Breast Cancer Stem Cell Isolation. AB - Cells within the tumor are highly heterogeneous. Only a small portion of the cells within the tumor is capable to generate a new tumor. These cells are called cancer stem cells. Theoretically, cancer stem cells are originally from normal stem cells or early progenitor cells which accumulate the random mutations and undergo an altered version of the normal differentiation process. The cancer stem cell drives tumor progression and its recurrence. Thus, the technique to identify and purify the cancer stem cell is the key in any cancer stem cell research. In this protocol, we provide the basic technology of identification and purification of breast cancer stem cells as well as further functional assays to help the researchers achieve their research goals. PMID- 26820951 TI - Cellular Apoptosis Assay of Breast Cancer. AB - Apoptosis is an energy-dependent enzymatic cell suicide process. It almost always involves the activation of caspases. In this chapter, we systemically introduce methodologies to assay caspases dependent biochemical and morphological changes in vitro breast cancer cell lines and in vivo breast cancer tissues. In addition, mitochondrial involvement is crucial to distinguish two different apoptotic pathways. Methodology to assay dissipation of mitochondrial transmembrane potential, an early event of mitochondrial involvement, is also included. Of note, since apoptotic features may not appear to the same extent depending on the context of cell types and the death-inducing insults, a common practice is to use more than one method to assess apoptosis, qualitatively and quantitatively. PMID- 26820952 TI - Assessment of Matrix Metalloproteinases by Gelatin Zymography. AB - Matrix metalloproteinases are endopeptidases responsible for remodeling of the extracellular matrix and have been identified as critical contributors to breast cancer progression. Gelatin zymography is a valuable tool which allows the analysis of MMP expression. In this approach, enzymes are resolved electrophoretically on a sodium dodecyl sulfate-polyacrylamide gel copolymerized with the substrate for the MMP of interest. Post electrophoresis, the enzymes are refolded in order for proteolysis of the incorporated substrate to occur. This assay yields valuable information about MMP isoforms or changes in activation and can be used to analyze the role of MMPs in normal versus pathological conditions. PMID- 26820953 TI - Assessment of Synthetic Matrix Metalloproteinase Inhibitors by Fluorogenic Substrate Assay. AB - Matrix metalloproteinases (MMPs) are a family of metzincin enzymes that act as the principal regulators and remodelers of the extracellular matrix (ECM). While MMPs are involved in many normal biological processes, unregulated MMP activity has been linked to many detrimental diseases, including cancer, neurodegenerative diseases, stroke, and cardiovascular disease. Developed as tools to investigate MMP function and as potential new therapeutics, matrix metalloproteinase inhibitors (MMPIs) have been designed, synthesized, and tested to regulate MMP activity. This chapter focuses on the use of enzyme kinetics to characterize inhibitors of MMPs. MMP activity is measured via fluorescence spectroscopy using a fluorogenic substrate that contains a 7-methoxycoumarin-4-acetic acid N succinimidyl ester (Mca) fluorophore and a 2,4-dinitrophenyl (Dpa) quencher separated by a scissile bond. MMP inhibitor (MMPI) potency can be determined from the reduction in fluorescent intensity when compared to the absence of the inhibitor. This chapter describes a technique to characterize a variety of MMPs through enzyme inhibition assays. PMID- 26820954 TI - Determination of Breast Cancer Cell Migratory Ability. AB - Cell migration is defined as the movement of individual cells, sheets of cells, or clusters of cells from one location to another (Friedl et al., Int J Dev Biol 48:441-449, 2004). This ability of cells to migrate is critical to a wide variety of normal and pathological processes, including embryonic development, wound healing, immune responses, and cancer (Leber et al., Int J Oncol 34:881-895, 2009). Migration of tumor cells is widely thought to be an essential component of the metastatic spread of tumor cells to new sites, and inhibiting metastasis is an important therapeutic goal in cancer treatments (Horwitz and Webb, Curr Biol 13:R756-759, 2003). Therefore, the ability to observe and quantify migration in cancer cells is critical not only for basic cancer biology but especially for drug development (Friedl and Gilmour, Nat Rev Mol Cell Biol 10: 445-457, 2009). Researchers continue to develop new techniques for measuring cell migration in vitro. This chapter will discuss two techniques commonly used to study cell migration: wound healing and Boyden chamber migration assays. PMID- 26820955 TI - A Novel Collagen Dot Assay for Monitoring Cancer Cell Migration. AB - Cell migration is a critical determinant of cancer invasion and metastasis. Drugs targeting cancer cell migration have been hindered due to the lack of effective assays for monitoring cancer cell migration. Here we describe a novel method to microscopically monitor cell migration in a quantitative fashion. This assay can be used to study genes involved in cancer cell migration, as well as screening anticancer drugs that target this cellular process. PMID- 26820956 TI - Three-Dimensional Assay for Studying Breast Cancer Cell Invasion. AB - Cancer cell invasion is a complex process that naturally occurs in a three dimensional (3-D) environment comprised of tumor cells and extracellular matrix components (ECM). Therefore, examining the invasive ability of breast cancer cells in a 3-D assay is imperative to discovering novel treatment strategies aimed at preventing cancer invasion and metastasis. Here, I describe a method to quantitatively measure the number of invaded cancer cells within a 3-D microenvironment and determine the effects of potential drugs on this cellular process. PMID- 26820957 TI - A Combined Phagocytosis and Fluorescent Substrate Degradation Assay to Simultaneously Assess Cell Migration and Substrate Degradation. AB - In order to more rapidly define the mechanism by which certain drugs and compounds can influence cancer cell invasion, we have combined a traditional phagokinetic gold migration assay with a fluorescent substrate. The purpose of this dual assay is to provide a platform by which to simultaneously monitor proteolytic activity and cancer cell migratory ability, both of which are required for the crucial step of cancer cell invasion during metastasis. This assay allows for delineation of potential mechanisms of action a compound of interest has, as one can determine whether or not a cancer cell that is being treated with the potential drug has changes in proteolytic activity and/or migratory ability at the same time. PMID- 26820958 TI - Analysis of Invadopodia Formation in Breast Cancer Cells. AB - Metastasis is the major cause of breast cancer deaths. To spread from the primary tumor sites to distant tissues, solid tumor cells need to degrade the surrounding extracellular matrix (ECM). The protrusive membrane structures named invadopodia have been shown to play a critical role in the degradation of the ECM and invasion of invasive cancer cells. In this chapter, we describe a detailed protocol to examine invadopodia in human breast cancer cells. PMID- 26820959 TI - Patient-Derived Tumor Xenograft Models of Breast Cancer. AB - The need for model systems that more accurately predict patient outcome has led to a renewed interest and a rapid development of orthotopic transplantation models designed to grow, expand, and study patient-derived human breast tumor tissue in mice. After implanting a human breast tumor piece into a mouse mammary fat pad and allowing the tumor to grow in vivo, the tumor tissue can be either harvested and immediately implanted into mice or can be stored as tissue pieces in liquid nitrogen for surgical implantation at a later time. Here, we describe the process of surgically implanting patient-derived breast tumor tissue into the mammary gland of nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice and harvesting tumor tissue for long-term storage in liquid nitrogen. PMID- 26820960 TI - Monitoring Phosphatidic Acid Signaling in Breast Cancer Cells Using Genetically Encoded Biosensors. AB - Phospholipids are important signaling molecules that regulate cell proliferation, death, migration, and metabolism. Many phospholipid signaling cascades are altered in breast cancer. To understand the functions of phospholipid signaling molecules, genetically encoded phospholipid biosensors have been developed to monitor their spatiotemporal dynamics. Compared to other phospholipids, much less is known about the subcellular production and cellular functions of phosphatidic acid (PA), partially due to the lack of a specific and sensitive PA biosensor in the past. This chapter describes the use of a newly developed PA biosensor, PASS, in two applications: regular fluorescent microscopy and fluorescence lifetime imaging microscopy-Forster/fluorescence resonance energy transfer (FLIM-FRET). These protocols can be also used with other phospholipid biosensors. PMID- 26820962 TI - Methods for Analyzing Tumor Angiogenesis in the Chick Chorioallantoic Membrane Model. AB - Models of tumor angiogenesis have played a critical role in understanding the mechanisms involved in the recruitment of vasculature to the tumor mass, and have also provided a platform for testing antiangiogenic potential of new therapeutics that combat the development of malignant growth. In this regard, the chorioallantoic membrane (CAM) of the developing chick embryo has proven to be an elegant model for investigation of angiogenic processes. Here, we describe methods for effectively utilizing the preestablished vascular network of the chick CAM to investigate and quantify tumor-associated angiogenesis in a breast tumor model. PMID- 26820961 TI - 3D In Vitro Model for Breast Cancer Research Using Magnetic Levitation and Bioprinting Method. AB - Tumor microenvironment composition and architecture are known as a major factor in orchestrating the tumor growth and its response to various therapies. In this context, in vivo studies are necessary to evaluate the responses. However, while tumor cells can be of human origin, tumor microenvironment in the in vivo models is host-based. On the other hand, in vitro studies in a flat monoculture of tumor cells (the most frequently used in vitro tumor model) are unable to recapitulate the complexity of tumor microenvironment. Three-dimensional (3D) in vitro cell cultures of tumor cells have been proven to be an important experimental tool in understanding mechanisms of tumor growth, response to therapeutics, and transport of nutrients/drugs. We have recently described a novel tool to create 3D co cultures of tumor cells and cells in the tumor microenvironment. Our method utilizes magnetic manipulation/levitation of the specific ratios of tumor cells and cells in the tumor microenvironment (from human or animal origin) aiding in the formation of tumor spheres with defined cellular composition and density, as quickly as within 24 h. This chapter describes the experimental protocols developed to model the 3D structure of the cancer environment using the above method. PMID- 26820963 TI - Pharmacokinetics and Pharmacodynamics in Breast Cancer Animal Models. AB - The study of pharmacokinetics (PK) and pharmacodynamics (PD) in cancer drug discovery and development is often paired and described in reciprocal terms, where PK is the analysis of the change in drug concentration with time and PD is the analysis of the biological effects of the drug at various concentrations over different time courses. While PK is defined by how a compound is absorbed, distributed, metabolized, and eliminated, PD refers to the measure of a compound's ability to interact with its intended target, leading to a biologic effect. Recent advances in anti-breast cancer drug discovery have resulted in several new drugs, but there is still a high attrition rate during clinical development. One reason for this failure is attributed to inappropriate correlation between the PK and PD parameters and subsequent extrapolation to human subjects. In this chapter, we describe the protocols of PK and PD studies in breast cancer models to assess the efficacy of an anti-breast cancer compound, noting the types and endpoints employed, and explain why it is important to link PK and PD in order to establish and evaluate dose/concentration-response relationships and subsequently describe and predict the effect-time courses for a given drug dose. PMID- 26820964 TI - Intracellular Delivery of Fluorescently Labeled Polysaccharide Nanoparticles to Cultured Breast Cancer Cells. AB - Nanoparticle delivery is becoming an increasingly more valuable technique in cancer drug treatments. The use of fluorescent probes, in particular, can provide noninvasive strategies to interrogate the internalization mechanisms of cancer cells and aid in drug design. Here we describe the delivery of fluorescently labeled polysaccharide-based nanoparticles to breast cancer cells in vitro and their subsequent immunofluorescence microscopy examination. The description of the synthesis, preparation, and delivery of the nanoparticles can be widely applicable to other in vitro drug delivery studies. PMID- 26820965 TI - Imaging Matrix Metalloproteinase Activity Implicated in Breast Cancer Progression. AB - Proteolysis has been cited as an important contributor to cancer initiation and progression. One can take advantage of tumor-associated proteases to selectively deliver imaging agents. Protease-activated imaging systems have been developed using substrates designed for hydrolysis by members of the matrix metalloproteinase (MMP) family. We presently describe approaches by which one can optically image matrix metalloproteinase activity implicated in breast cancer progression, with consideration of selective versus broad protease probes. PMID- 26820966 TI - Biomechanical evaluation of MPFL reconstructions: differences in dynamic contact pressure between gracilis and fascia lata graft. AB - PURPOSE: To evaluate the knee kinematics of the intact, MPFL-ruptured and MPFL reconstructed knee and, moreover, to compare dynamic patellofemoral contact pressure of the gracilis tendon and the fascia lata as an alternative graft option for reconstruction of the MPFL. METHODS: Eight paired human cadaveric knees were fixed in a custom-made fixation device. Patellofemoral contact pressure was assessed during a dynamic flexion movement at 15 degrees -30 degrees -45 degrees -60 degrees -75 degrees and 90 degrees using a pressure-sensitive film (Tekscan). The medial patellofemoral ligament was cut, and measurements were repeated. Finally, reconstruction of the MPFL was performed using the gracilis tendon (group I) or a fascia lata graft (group II). Tunnel localization was performed under fluoroscopic control. Grafts were fixed at 30 degrees of flexion, and pressure measurements were repeated. RESULTS: Incision of the medial patellofemoral ligament significantly reduced patellofemoral contact pressure at 15 degrees , 30 degrees and 45 degrees of knee flexion compared to the intact knee (p < 0.05), whereas reconstruction of the MPFL using either gracilis tendon of the fascia lata was able to restore pressure distributions at 15 degrees and 30 degrees of knee flexion. However, in the hamstring group, reconstruction of the MPFL revealed a significantly reduced contact pressure at 45 degrees of flexion (p = 0.038) compared to the intact knee. In the fascia lata group, a significant reduction in patellofemoral contact pressure was observed after MPFL reconstruction at 45 degrees , 60 degrees , 75 degrees and 90 degrees of knee flexion (p < 0.05). CONCLUSIONS: Anatomic reconstruction of the MPFL with either a gracilis or a fascia lata graft showed comparable patellofemoral pressure distributions which were closely restored compared to the native knee. Therefore, the fascia lata has shown to be a viable alternative to the gracilis tendon for reconstruction of the MPFL. However, anatomic reconstruction of the MPFL may lead to persistently altered patellofemoral contact pressure during knee flexion compared to the native knee independent of the tested graft. PMID- 26820967 TI - Changes in sagittal component alignment alters patellar kinematics in TKA: an in vitro study. AB - PURPOSE: Patellar maltracking due to incorrect component alignment is considered as a main reason for anterior knee pain after total knee arthroplasty (TKA). In contrast to coronal and axial component placement, the influence of sagittal component alignment on patellar kinematics has not been investigated so far. METHODS: In ten lower cadaveric limbs, TKAs were implanted using a commercial computer navigation system. In six knees, the femoral component was aligned in 5 degrees and in four knees in 0 degrees of flexion, respectively. Patellar kinematics were registered by means of a computer navigation system using an additional patella tracking array and correlated with femoral and tibial sagittal component alignment. RESULTS: Sagittal component alignment significantly altered patellar mediolateral shift (p < 0.05). In contrast, patellar epicondylar distance, rotation and tilt were not significantly influenced. CONCLUSIONS: Sagittal component alignment in TKA has a major impact on patellar kinematics and should therefore be considered while addressing tibiofemoral kinematics intraoperatively. PMID- 26820968 TI - High Frequency of Pulmonary Hypertension-Causing Gene Mutation in Chinese Patients with Chronic Thromboembolic Pulmonary Hypertension. AB - The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is unknown. Histopathologic studies revealed that pulmonary vasculature lesions similar to idiopathic pulmonary arterial hypertension (PAH) existed in CTEPH patients as well. It's well-known that genetic predisposition plays an important role in the mechanism of PAH. So we hypothesized that PAH-causing gene mutation might exist in some CTEPH patients and act as a background to facilitate the development of CTEPH. In this study, we analyzed 7 PAH-causing genes including BMPR2, ACVRL1, ENG, SMAD9, CAV1, KCNK3, and CBLN2 in 49 CTEPH patients and 17 patients recovered from pulmonary embolism (PE) but without pulmonary hypertension(PH). The results showed that the nonsynonymous mutation rate in CTEPH patients is significantly higher than that in PE without PH patients (25 out of 49 (51%) CTEPH patients vs. 3 out of 17 PE without PH patients (18%); p = 0.022). Four CTEPH patients had the same point mutation in ACVRL1 exon 10 (c.1450C>G), a mutation approved to be associated with PH in a previous study. In addition, we identified two CTEPH associated SNPs (rs3739817 and rs55805125). Our results suggest that PAH-causing gene mutation might play an important role in the development of CTEPH. PMID- 26820969 TI - Effect of Single Intravitreal Bevacizumab on Ophthalmic and Middle Cerebral Arterial Blood Flow in Retinopathy of Prematurity. AB - PURPOSE: To evaluate the effect of a single intravitreal bevacizumab (IVB) injection on blood flow parameters in the ophthalmic artery (OA) and middle cerebral artery (MCA) in infants with retinopathy of prematurity (ROP). MATERIALS AND METHODS: This prospective and interventional study included 15 infants with ROP who were treated with IVB. Peak systolic velocity (PSV), end-diastolic velocity, mean velocity (MV) and resistivity index were measured using pulse wave Doppler ultrasonography (Philips En Visor C, Amsterdam, The Netherlands) in the OA and MCA, before IVB injection and 1 day, 1 week and 1 month after IVB injection. RESULTS: Measurements of PSV-OA, MV-OA and PSV-MCA showed significant changes after IVB treatment (p = 0.01, p = 0.02, p = 0.02, respectively). The PSV OA measurements at 1 week and 1 month were significantly lower than the baseline PSV-OA measurement (p = 0.03 and p = 0.01, respectively). The MV-OA measurement was significantly lower at 1 month following IVB as compared to the baseline MV OA measurement (p = 0.03). The PSV-MCA showed a significant decline 1 day after IVB injection (p = 0.03). CONCLUSIONS: The study demonstrated that IVB causes significant alterations in blood flow parameters in the OA and MCA predicted by Doppler ultrasonography in infants with ROP. PMID- 26820971 TI - Extract of Calvatia gigantea inhibits proliferation of A549 human lung cancer cells. AB - In this study, in order to investigate the anticancer mechanism of Calvatia gigantea extract, edible mushroom species, which belong to Lycoperdaceae family, changes of CCND1, CCND2, CDK4, p21, Akt, Bax, Bcl-2, p53, caspase-3 and caspase-9 were evaluated in A549 lung cancer cells. Cytotoxic effect of C. gigantea extract was evaluated by using XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H tetrazolium-5 carboxanilide). The C. gigantea extract was treated in a time and dose dependent manner within the range 25 MUg/ml-2 mg/ml to determine the IC50 dose. IC50 dose for C. gigantea extract was detected as 500 MUg/ml for 72 h. According to expression results, while CCND1, CCND2, CDK4, Akt and Bcl-2 expression clearly decreased, Bax, p53, caspase-3 and caspase-9 expression clearly increased in the dose group cells (A549 cells treated with 500 MUg/ml dose of C. gigantea extract for 72 h). However, there was no change in p21 expression. C. gigantea extract induced cell cycle arrest and apoptosis by decreasing the CCND1, CCND2, CDK4, Akt and Bcl-2 expression and by increasing Bax, p53, caspase-3 and caspase-9 expression in A549 cells. Mushrooms are eukaryotic organisms heavily used because of their supposedly anticancer effect. Many mushroom species have been used for medical purposes, as a result of also having many effects such as antibiotic, antiviral and anticancer effects. It is thought that the C. gigantea extract may be a significant agent for treatment of lung cancer as a single agent or in combination with other drugs. PMID- 26820970 TI - Analysis of Lymphocytic DNA Damage in Early Multiple Sclerosis by Automated Gamma H2AX and 53BP1 Foci Detection: A Case Control Study. AB - BACKGROUND: In response to DNA double-strand breaks, the histone protein H2AX becomes phosphorylated at its C-terminal serine 139 residue, referred to as gamma H2AX. Formation of gamma-H2AX foci is associated with recruitment of p53-binding protein 1 (53BP1), a regulator of the cellular response to DNA double-strand breaks. gamma-H2AX expression in peripheral blood mononuclear cells (PBMCs) was recently proposed as a diagnostic and disease activity marker for multiple sclerosis (MS). OBJECTIVE: To evaluate the significance of gamma-H2AX and 53BP1 foci in PBMCs as diagnostic and disease activity markers in patients with clinically isolated syndrome (CIS) and early relapsing-remitting MS (RRMS) using automated gamma-H2AX and 53BP1 foci detection. METHODS: Immunocytochemistry was performed on freshly isolated PBMCs of patients with CIS/early RRMS (n = 25) and healthy controls (n = 27) with gamma-H2AX and 53BP1 specific antibodies. Nuclear gamma-H2AX and 53BP1 foci were determined using a fully automated reading system, assessing the numbers of gamma-H2AX and 53BP1 foci per total number of cells and the percentage of cells with foci. Patients underwent contrast enhanced 3 Tesla magnetic resonance imaging (MRI) and clinical examination including expanded disability status scale (EDSS) score. gamma-H2AX and 53BP1 were also compared in previously frozen PBMCs of each 10 CIS/early RRMS patients with and without contrast enhancing lesions (CEL) and 10 healthy controls. RESULTS: The median (range) number of gamma-H2AX (0.04 [0-0.5]) and 53BP1 (0.005 [0-0.2]) foci per cell in freshly isolated PBMCs across all study participants was low and similar to previously reported values of healthy individuals. For both, gamma-H2AX and 53BP1, the cellular focus number as well as the percentage of positive cells did not differ between patients with CIS/RRMS and healthy controls. gamma-H2AX and 53BP1 levels neither correlated with number nor volume of T2-weighted lesions on MRI, nor with the EDSS. Although gamma-H2AX, but not 53BP1, levels were higher in previously frozen PBMCs of patients with than without CEL, gamma-H2AX values of both groups overlapped and gamma-H2AX did not correlate with the number or volume of CEL. CONCLUSION: gamma-H2AX and 53BP1 foci do not seem to be promising diagnostic or disease activity biomarkers in patients with early MS. Lymphocytic DNA double-strand breaks are unlikely to play a major role in the pathophysiology of MS. PMID- 26820972 TI - Generation and characterization of human cardiac resident and non-resident mesenchymal stem cell. AB - Despite the surgical and other insertional interventions, the complete recuperation of myocardial disorders is still elusive due to the insufficiency of functioning myocardiocytes. Thus, the use of stem cells to regenerate the affected region of heart becomes a prime important. In line with this human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have gained considerable interest due to their potential use for mesodermal cell based replacement therapy and tissue engineering. Since MSCs are harvested from various organs and anatomical locations of same organism, thus the cardiac regenerative potential of human cardiac-derived MSCs (hC-MSCs) and human umbilical cord Wharton's Jelly derived MSC (hUC-MSCs) were tested concurrently. At in vitro culture, both hUC MSCs and hC-MSCs assumed spindle shape morphology with expression of typical MSC markers namely CD105, CD73, CD90 and CD44. Although, hUC-MSCs and hC-MSCs are identical in term of morphology and immunophenotype, yet hUC-MSCs harbored a higher cell growth as compared to the hC-MSCs. The inherent cardiac regenerative potential of both cells were further investigated with mRNA expression of ion channels. The RT-PCR results demonstrated that both MSCs were expressing a notable level of delayed rectifier-like K(+) current (I KDR ) ion channel, yet the relative expression level was considerably varied between hUC-MSCs and hC MSCs that Kv1.1(39 +/- 0.6 vs 31 +/- 0.8), Kv2.1 (6 +/- 0.2 vs 21 +/- 0.12), Kv1.5 (7.4 +/- 0.1 vs 6.8 +/- 0.06) and Kv7.3 (27 +/- 0.8 vs 13.8 +/- 0.6). Similarly, the Ca2(+)-activated K(+) current (I KCa ) channel encoding gene, transient outward K(+) current (I to ) and TTX-sensitive transient inward sodium current (I Na.TTX ) encoding gene (Kv4.2, Kv4.3 and hNE-Na) expressions were detected in both groups as well. Despite the morphological and phenotypical similarity, the present study also confirms the existence of multiple functional ion channel currents IKDR, IKCa, Ito, and INa.TTX in undifferentiated hUC-MSCs as of hC-MSCs. Thus, the hUC-MSCs can be exploited as a potential candidate for future cardiac regeneration. PMID- 26820973 TI - A study to identify and characterize the stem/progenitor cell in rabbit meniscus. AB - The repair of meniscus in the avascular zone remains a great challenge, largely owing to their limited healing capacity. Stem cells based tissue engineering provides a promising treatment option for damaged meniscus because of their multiple differentiation potential. We hypothesized that meniscus-derived stromal cells (MMSCs) may be present in meniscal tissue, and if their pluripotency and character can be established, they may play a role in meniscal healing. To test our hypothesis, we isolated MMSCs, bone marrow-derived stromal cells (BMSCs) and fibrochondrocytes from rabbits. In order to avoid bone marrow mesenchymal stromal cell contamination, the parameniscal tissues and vascular zone of meniscus were removed. The characters of these three types of cells were identified by evaluating morphology, colony formation, proliferation, immunocytochemistry and multi-differentiation. Moreover, a wound in the center of rabbit meniscus was created and used to analyze the effect of BMSCs and MMSCs on wounded meniscus healing. BMSCs & MMSCs expressed the stem cell markers SSEA-4, Nanog, nucleostemin and STRO-1, while fibrochondrocytes expressed none of these markers. Morphologically, MMSCs displayed smaller cell bodies and larger nuclei than ordinary fibrochondrocytes. Moreover, it was certified that MMSCs and BMSCs were all able to differentiate into adipocytes, osteocytes, and chondrocytes in vitro. However, more cartilage formation was found in wounded meniscus filled with MMSCs than that filled with BMSCs. We showed that rabbit menisci harbor the unique cell population MMSCs that has universal stem cell characteristics and posses a tendency to differentiate into chondrocytes. Future research should investigate the mechanobiology of MMSCs and explore the possibility of using MMSCs to more effectively repair or regenerate injured meniscus. PMID- 26820974 TI - Mobility and chemical fate of arsenic and antimony in water and sediments of Sarouq River catchment, Takab geothermal field, northwest Iran. AB - Arsenic (As) and antimony (Sb) concentrations in water and sediments were determined along flow paths in the Sarouq River, Zarshuran and Agh Darreh streams. The results indicate high As and Sb concentrations in water and sediment samples. Raman spectroscopy shows hematite (alpha-Fe2O3), goethite [alpha FeO(OH)] and lepidocrocite [gamma-FeO(OH)] in sediment samples. Calculated saturation indices (SI) indicate oversaturation with respect to amorphous Fe(OH)3 for all samples, but undersaturation with respect to Al and Mn mineral and amorphous phases. Therefore, ferric oxides and hydroxides are assumed to be principal mineral phases for arsenic and antimony attenuation by adsorption/co precipitation processes. The considerable difference between As and Sb concentration in sediment is due to strong adsorption of As(V) into the solid phase. Also, lower affinity of Sb(V) for mineral surfaces suggests a greater potential for aqueous transport. The adsorption of arsenic and antimony was examined using the Freundlich adsorption isotherm to determine their distribution model in water-sediment system and its compatibility with the existing theoretical model. The results showed that the adsorption behavior of both elements complies with the Freundlich adsorption isotherm. PMID- 26820975 TI - Voriconazole-induced skeletal fluorosis in an allogenic hematopoietic stem cell transplant recipient. PMID- 26820976 TI - Discovery of a Bacterial Glycoside Hydrolase Family 3 (GH3) beta-Glucosidase with Myrosinase Activity from a Citrobacter Strain Isolated from Soil. AB - A Citrobacter strain (WYE1) was isolated from a UK soil by enrichment using the glucosinolate sinigrin as sole carbon source. The enzyme myrosinase was purified using a combination of ion exchange and gel filtration to give a pure protein of approximately 66 kDa. The N-terminal amino acid and internal peptide sequence of the purified protein were determined and used to identify the gene, which, based on InterPro sequence analysis, belongs to the family GH3, contains a signal peptide, and is a periplasmic protein with a predicted molecular mass of 71.8 kDa. A preliminary characterization was carried out using protein extracts from cell-free preparations. The apparent KM and Vmax were 0.46 mM and 4.91 mmol dm( 3) min(-1) mg(-1), respectively, with sinigrin as substrate. The optimum temperature and pH for enzyme activity were 25 degrees C and 6.0, respectively. The enzyme was marginally activated with ascorbate by a factor of 1.67. PMID- 26820977 TI - Relative Leukocyte Telomere Length, Hematological Parameters and Anemia - Data from the Berlin Aging Study II (BASE-II). AB - BACKGROUND: The length of the chromosome ends, telomeres, is widely accepted as a biomarker of aging. However, the dynamic of the relationship between telomere length and hematopoietic parameters in the normal aging process, which is of particular interest with respect to age-related anemia, is not well understood. OBJECTIVE: We have analyzed the relationship between relative leukocyte telomere length (rLTL) and several hematological parameters in the older group of the Berlin Aging Study II (BASE-II) participants. This paper also compares rLTL between both BASE-II age groups (22-37 and 60-83 years). METHODS: Genomic DNA was extracted from peripheral blood leukocytes of BASE-II participants and used to determine rLTL by a quantitative PCR protocol. Standard methods were used to determine blood parameters, and the WHO criteria were used to identify anemic participants. RESULTS: Telomere length data were available for 444 younger participants (28.4 +/- 3.1 years old; 52% women) and 1,460 older participants (68.2 +/- 3.7 years old; 49.4% women). rLTL was significantly shorter in BASE-II participants of the older group (p = 3.7 * 10-12) and in women (p = 4.2 * 10-31). rLTL of older men exhibited a statistically significant, positive partial correlation with mean corpuscular hemoglobin (MCH; p = 0.012) and MCH concentration (p = 0.002). While these correlations were only observed in men, the rLTL of older women was negatively correlated with the number of thrombocytes (p = 0.015) in the same type of analysis. Among all older participants, 6% met the criteria to be categorized as 'anemic'; however, there was no association between anemia and rLTL. CONCLUSION: In the present study, we have detected isolated correlations between rLTL and hematological parameters; however, in all cases, rLTL explained only a small part of the variation of the analyzed parameters. In disagreement with some other studies showing similar data, we interpret the association between rLTL and some of the hematological parameters studied here to be at most marginal. This applies also to the role of rLTL in anemia, at least in the age group investigated here. Since BASE-II is yet another large cohort in which women have on average shorter telomeres than men, this finding will be addressed in the discussion with respect to the ongoing debate on gender differences in telomere length. PMID- 26820978 TI - Differences in Anticipatory Behaviour between Rats (Rattus norvegicus) Housed in Standard versus Semi-Naturalistic Laboratory Environments. AB - Laboratory rats are usually kept in relatively small cages, but research has shown that they prefer larger and more complex environments. The physiological, neurological and health effects of standard laboratory housing are well established, but fewer studies have addressed the sustained emotional impact of a standard cage environment. One method of assessing affective states in animals is to look at the animals' anticipatory behaviour between the presentation of a cue signalling the arrival of a reward and the arrival of that reward. The primary aim of this study was to use anticipatory behaviour to assess the affective state experienced by female rats a) reared and housed long-term in a standard laboratory cage versus a semi-naturalistic environment, and b) before and after treatment with an antidepressant or an anxiolytic. A secondary aim was to add to the literature on anticipatory behaviour by describing and comparing the frequency and duration of individual elements of anticipatory behaviour displayed by rats reared in these two systems. In all experiments, total behavioural frequency was higher in standard-housed rats compared to rats from the semi naturalistic condition, suggesting that standard-housed rats were more sensitive to rewards and experiencing poorer welfare than rats reared in the semi naturalistic environment. What rats did in anticipation of the reward also differed between housing treatments, with standard-housed rats mostly rearing and rats from the semi-naturalistic condition mostly sitting facing the direction of the upcoming treat. Drug interventions had no effect on the quantity or form of anticipatory behaviour, suggesting that the poorer welfare experienced by standard-housed rats was not analogous to depression or anxiety, or alternatively that the drug interventions were ineffective. This study adds to mounting evidence that standard laboratory housing for rats compromises rat welfare, and provides further scientific support for recommendations that current minimum standards be raised. PMID- 26820979 TI - Erratum to: Re-irradiation of recurrent anaplastic ependymoma using radiosurgery or fractionated stereotactic radiotherapy. PMID- 26820981 TI - Savior of post-blepharoepicanthoplasty scarring: Novel use of a low-fluence 1064 nm Q-switched Nd:YAG laser. AB - Blepharoplasty with medial epicanthoplasty is popular in Asia. However, known complications include scarring, which can take the form of hypertrophic scars or keloids. Treatments for scars include pressure dressing, silicone gels, retinoic acids, radiotherapy, cryotherapy, triamcinolone injections, and surgical revision. These methods, however, have variable outcomes. Recently, there is an interest in post-surgical scar remodeling with lasers. Although the 1064-nm Q switched Nd:YAG is primarily a pigment laser, it has recently been shown to be effective for treating scars. In the management of post-blepharoepicanthoplasty scarring, this is certainly unheard of. In this paper, we present a novel technique of treating a patient with post-blepharoepicanthoplasty hypertrophic scarring with a low-fluence 1064-nm Q-switched Nd:YAG laser. PMID- 26820980 TI - Utility of dual source CT with ECG-triggered high-pitch spiral acquisition (Flash Spiral Cardio mode) to evaluate morphological features of ventricles in children with complex congenital heart defects. AB - PURPOSE: We evaluated the ability of dual source CT (DSCT) with ECG-triggered high-pitch spiral acquisition (Flash Spiral Cardio mode) to depict the morphological features of ventricles in pediatric patients with congenital heart defects (CHD). MATERIALS AND METHODS: Between July 2013 and April 2015, 78 pediatric patients with CHD (median age 4 months) were examined using DSCT with the Flash Spiral Cardio mode. The types of ventricular abnormalities were ventricular septal defect (VSD) in 42 (the malaligned type in 11, perimembranous type in 23, supracristal type in 2, atrioventricular type in 2, and muscular type in 4), single ventricle (SV) in 11, and congenital corrected transposition of the great arteries (ccTGA) in 4. We evaluated the accuracy of the diagnosis of the VSD type. In cases of SV and ccTGA, we assessed the detectability of the anatomical features of both ventricles for a diagnosis of ventricular situs. RESULTS: DSCT confirmed the diagnoses for all VSDs. The type of defect was precisely diagnosed for all patients. The anatomical features of both ventricles were also depicted and ventricular situs of SV and ccTGA was correctly diagnosed. CONCLUSION: The results suggest that DSCT has the ability to clearly depict the configuration of ventricles. PMID- 26820982 TI - Economic Evaluation of Individual School Closure Strategies: The Hong Kong 2009 H1N1 Pandemic. AB - BACKGROUND: School closures as a means of containing the spread of disease have received considerable attention from the public health community. Although they have been implemented during previous pandemics, the epidemiological and economic effects of the closure of individual schools remain unclear. METHODOLOGY: This study used data from the 2009 H1N1 pandemic in Hong Kong to develop a simulation model of an influenza pandemic with a localised population structure to provide scientific justifications for and economic evaluations of individual-level school closure strategies. FINDINGS: The estimated cost of the study's baseline scenario was USD330 million. We found that the individual school closure strategies that involved all types of schools and those that used a lower threshold to trigger school closures had the best performance. The best scenario resulted in an 80% decrease in the number of cases (i.e., prevention of about 830,000 cases), and the cost per case prevented by this intervention was USD1,145; thus, the total cost was USD1.28 billion. CONCLUSION: This study predicts the effects of individual school closure strategies on the 2009 H1N1 pandemic in Hong Kong. Further research could determine optimal strategies that combine various system wide and district-wide school closures with individual school triggers across types of schools. The effects of different closure triggers at different phases of a pandemic should also be examined. PMID- 26820983 TI - Glycemic Control in Coronary Revascularization. AB - OPINION STATEMENT: Hyperglycemia in the setting of coronary revascularization is associated with increased adverse cardiovascular events in patients with or without diabetes mellitus. Data suggest that acute peri-procedural hyperglycemia causes an increase in inflammation, platelet activity, and endothelial dysfunction and is associated with plaque instability and infarct size. While peri-procedural blood glucose level is an independent predictor of adverse outcomes in patients undergoing coronary revascularization, treatment strategies remain uncertain. Randomized clinical trials of glucose-insulin-potassium infusions have consistently shown no benefit, while those comparing insulin therapy versus standard of care have demonstrated mixed results, likely due to the failure to reach euglycemia with these strategies. Although no glucose lowering agent has been shown to be superior in peri-procedural glycemic control, the continuation of clinically prescribed long-acting glucose-lowering medications in patients with diabetes mellitus prior to coronary angiography and possible percutaneous coronary intervention may be the simplest and most effective approach to maintain euglycemia and decrease the associated increase in inflammation and platelet activity. However, alternative strategies such as therapies targeted at the underlying mechanism of harm (e.g., more potent anti platelet therapy, anti-inflammatory therapy) should also be considered and warrant further investigation. PMID- 26820985 TI - Abstracts from the Fifth American Cough Conference. PMID- 26820984 TI - Biomolecular Characterization of Putative Antidiabetic Herbal Extracts. AB - Induction of GLUT4 translocation in the absence of insulin is considered a key concept to decrease elevated blood glucose levels in diabetics. Due to the lack of pharmaceuticals that specifically increase the uptake of glucose from the blood circuit, application of natural compounds might be an alternative strategy. However, the effects and mechanisms of action remain unknown for many of those substances. For this study we investigated extracts prepared from seven different plants, which have been reported to exhibit anti-diabetic effects, for their GLUT4 translocation inducing properties. Quantitation of GLUT4 translocation was determined by total internal reflection fluorescence (TIRF) microscopy in insulin sensitive CHO-K1 cells and adipocytes. Two extracts prepared from purslane (Portulaca oleracea) and tindora (Coccinia grandis) were found to induce GLUT4 translocation, accompanied by an increase of intracellular glucose concentrations. Our results indicate that the PI3K pathway is mainly responsible for the respective translocation process. Atomic force microscopy was used to prove complete plasma membrane insertion. Furthermore, this approach suggested a compound mediated distribution of GLUT4 molecules in the plasma membrane similar to insulin stimulated conditions. Utilizing a fluorescent actin marker, TIRF measurements indicated an impact of purslane and tindora on actin remodeling as observed in insulin treated cells. Finally, in-ovo experiments suggested a significant reduction of blood glucose levels under tindora and purslane treated conditions in a living organism. In conclusion, this study confirms the anti diabetic properties of tindora and purslane, which stimulate GLUT4 translocation in an insulin-like manner. PMID- 26820986 TI - Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance? AB - High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the best approach for controlling resistance therefore depends on the relative strengths of these processes. These opposing processes typically lead to a unimodal relationship between drug pressure and resistance emergence. As a result, the optimal drug dose lies at either end of the therapeutic window of clinically acceptable concentrations. We illustrate our findings with a simple model that shows how a seemingly minor change in parameter values can alter the outcome from one where high-dose chemotherapy is optimal to one where using the smallest clinically effective dose is best. A review of the available empirical evidence provides broad support for these general conclusions. Our analysis opens up treatment options not currently considered as resistance management strategies, and it also simplifies the experiments required to determine the drug doses which best retard resistance emergence in patients. PMID- 26820989 TI - Computed Tomography Perfusion Improves Diagnostic Accuracy in Acute Posterior Circulation Stroke. AB - BACKGROUND AND PURPOSE: Computed tomography perfusion (CTP) has a high diagnostic value in the detection of acute ischemic stroke in the anterior circulation. However, the diagnostic value in suspected posterior circulation (PC) stroke is uncertain, and whole brain volume perfusion is not yet in widespread use. We therefore studied the additional value of whole brain volume perfusion to non contrast CT (NCCT) and CT angiography source images (CTA-SI) for infarct detection in patients with suspected acute ischemic PC stroke. METHODS: This is a retrospective review of patients with suspected stroke in the PC in a database of our stroke center (n = 3,011) who underwent NCCT, CTA and CTP within 9 h after stroke onset and CT or MRI on follow-up. Images were evaluated for signs and pc ASPECTS locations of ischemia. Three imaging models - A (NCCT), B (NCCT + CTA-SI) and C (NCCT + CTA-SI + CTP) - were compared with regard to the misclassification rate relative to gold standard (infarction in follow-up imaging) using the McNemar's test. RESULTS: Of 3,011 stroke patients, 267 patients had a suspected stroke in the PC and 188 patients (70.4%) evidenced a PC infarct on follow-up imaging. The sensitivity of Model C (76.6%) was higher compared with that of Model A (21.3%) and Model B (43.6%). CTP detected significantly more ischemic lesions, especially in the cerebellum, posterior cerebral artery territory and thalami. CONCLUSIONS: Our findings in a large cohort of consecutive patients show that CTP detects significantly more ischemic strokes in the PC than CTA and NCCT alone. PMID- 26820987 TI - Differential Protein Expression Profiles in Glaucomatous Trabecular Meshwork: An Evaluation Study on a Small Primary Open Angle Glaucoma Population. AB - INTRODUCTION: Primary open angle glaucoma (POAG) is a progressive optic neuropathy characterized by impaired aqueous outflow and extensive remodeling in the trabecular meshwork (TM). The aim of this study was to characterize and compare the expression patterns of selected proteins belonging to the tissue remodeling, inflammation and growth factor pathways in ex vivo glaucomatous and post-mortem TMs using protein-array analysis. METHODS: TM specimens were collected from 63 white subjects, including 40 patients with glaucoma and 23 controls. Forty POAG TMs were collected at the time of surgery and 23 post-mortem specimens were from non-glaucomatous donor sclerocorneal tissues. Protein profiles were evaluated using a chip-based array consisting of 60 literature selected antibodies. RESULTS: A different expression of some factors was observed in POAG TMs with respect to post-mortem specimens, either in abundance (interleukin [IL]10, IL6, IL5, IL7, IL12, IL3, macrophage inflammatory protein [MIP]1delta/alpha, vascular endothelial growth factor [VEGF], transforming growth factor beta 1 [TGFbeta1], soluble tumor necrosis factor receptor I [sTNFRI]) or in scarcity (IL16, IL18, intercellular adhesion molecule 3 [ICAM3], matrix metalloproteinase-7 [MMP7], tissue inhibitor of metalloproteinase 1 [TIMP1]). MMP2, MMP7, TGFbeta1, and VEGF expressions were confirmed by Western blot, zymography, and polymerase chain reaction. No difference in protein profile expression was detected between glaucomatous subtypes. CONCLUSION: The analysis of this small TM population highlighted some proteins linked to POAG, some previously reported and others of new detection (IL7, MIPs, sTNFalphaRI). A larger POAG population is required to select promising disease-associated biomarker candidates. FUNDING: This study was partially supported by the Fondazione Roma, the Italian Ministry of Health and the "National 5xMille 2010 tax donation to IRCCS-G.B. Bietti Foundation". PMID- 26820990 TI - [Obesity in elderly]. AB - The prevalence of obesity is increasing also in the elderly population. The European Euronut-Seneca study described an obesity prevalence of 12-41% in elderly women and of 8-24% in elderly men. Obesity in the elderly is related to the cardiometabolic risk, but also to degenerative joint diseases and impaired physical functions. Some discrepancies are caused by the description of a so called obesity paradox with a more favourable prognosis for certain diseases in the presence of overweight compared to normal or reduced body weight. The so called sarcopenic obesity is associated with the worst prognosis.Preventive and therapeutic regimens should consider the increased risk of malnutrition in elderly. The combinations of individually tailored nutritional recommendations and physical exercise is of advantage for the prognosis of comorbidities and the quality of life. PMID- 26820991 TI - Scope for genetic rescue of an endangered subspecies though re-establishing natural gene flow with another subspecies. AB - Genetic diversity is positively linked to the viability and evolutionary potential of species but is often compromised in threatened taxa. Genetic rescue by gene flow from a more diverse or differentiated source population of the same species can be an effective strategy for alleviating inbreeding depression and boosting evolutionary potential. The helmeted honeyeater Lichenostomus melanops cassidix is a critically endangered subspecies of the common yellow-tufted honeyeater. Cassidix has declined to a single wild population of ~130 birds, despite being subject to intensive population management over recent decades. We assessed changes in microsatellite diversity in cassidix over the last four decades and used population viability analysis to explore whether genetic rescue through hybridization with the neighbouring Lichenostomus melanops gippslandicus subspecies constitutes a viable conservation strategy. The contemporary cassidix population is characterized by low genetic diversity and effective population size (N(e) < 50), suggesting it is vulnerable to inbreeding depression and will have limited capacity to evolve to changing environments. We find that gene flow from gippslandicus to cassidix has declined substantially relative to pre-1990 levels and argue that natural levels of gene flow between the two subspecies should be restored. Allowing gene flow (~4 migrants per generation) from gippslandicus into cassidix (i.e. genetic rescue), in combination with continued annual release of captive-bred cassidix (i.e. demographic rescue), should lead to positive demographic and genetic outcomes. Although we consider the risk of outbreeding depression to be low, we recommend that genetic rescue be managed within the context of the captive breeding programme, with monitoring of outcomes. PMID- 26820988 TI - ESTES guidelines: acute mesenteric ischaemia. AB - PURPOSE: Acute mesenteric ischaemia (AMI) accounts for about 1:1000 acute hospital admissions. Untreated, AMI will cause mesenteric infarction, intestinal necrosis, an overwhelming inflammatory response and death. Early intervention can halt and reverse this process leading to a full recovery, but the diagnosis of AMI is difficult and failure to recognize AMI before intestinal necrosis has developed is responsible for the high mortality of the disease. Early diagnosis and prompt treatment are the goals of modern therapy, but there are no randomized controlled trials to guide treatment and the published literature contains a high ratio of reviews to original data. Much of that data comes from case reports and often small, retrospective series with no clearly defined treatment criteria. METHODS: A study group of the European Society for Trauma and Emergency Surgery (ESTES) was formed in 2013 with the aim of developing guidelines for the management of AMI. A comprehensive literature search was performed using the Medical Subject Heading (MeSH) thesaurus keywords "mesenteric ischaemia", "bowel ischaemia" and "bowel infarction". The bibliographies of relevant articles were screened for additional publications. After an initial systematic review of the literature by the whole group, a steering group formulated questions using a modified Delphi process. The evidence was then reviewed to answer these questions, and recommendations formulated and agreed by the whole group. RESULTS: The resultant recommendations are presented in this paper. CONCLUSIONS: The aim of these guidelines is to provide recommendations for practice that will lead to improved outcomes for patients. PMID- 26820992 TI - Rad51c- and Trp53-double-mutant mouse model reveals common features of homologous recombination-deficient breast cancers. AB - Almost half of all hereditary breast cancers (BCs) are associated with germ-line mutations in homologous recombination (HR) genes. However, the tumor phenotypes associated with different HR genes vary, making it difficult to define the role of HR in BC predisposition. To distinguish between HR-dependent and -independent features of BCs, we generated a mouse model in which an essential HR gene, Rad51c, is knocked-out specifically in epidermal tissues. Rad51c is one of the key mediators of HR and a well-known BC predisposition gene. Here, we demonstrate that deletion of Rad51c invariably requires inactivation of the Trp53 tumor suppressor (TP53 in humans) to produce mammary carcinomas in 63% of female mice. Nonetheless, loss of Rad51c shortens the latency of Trp53-deficient mouse tumors from 11 to 6 months. Remarkably, the histopathological features of Rad51c deficient mammary carcinomas, such as expression of hormone receptors and luminal epithelial markers, faithfully recapitulate the histopathology of human RAD51C mutated BCs. Similar to other BC models, Rad51c/p53 double-mutant mouse mammary tumors also reveal a propensity for genomic instability, but lack the focal amplification of the Met locus or distinct mutational signatures reported for other HR genes. Using the human mammary epithelial cell line MCF10A, we show that deletion of TP53 can rescue RAD51C-deficient cells from radiation-induced cellular senescence, whereas it exacerbates their centrosome amplification and nuclear abnormalities. Altogether, our data indicate that a trend for genomic instability and inactivation of Trp53 are common features of HR-mediated BCs, whereas histopathology and somatic mutation patterns are specific for different HR genes. PMID- 26820993 TI - Composite vascular scaffold combining electrospun fibers and physically crosslinked hydrogel with copper wire-induced grooves structure. AB - While the field of tissue engineered vascular grafts has greatly advanced, many inadequacies still exist. Successfully developed scaffolds require mechanical and structural properties that match native vessels and optimal microenvironments that foster cell integration, adhesion and growth. We have developed a small diameter, three-layered composite vascular scaffold which consists of electrospun fibers and physically-crosslinked hydrogel with copper wire-induced grooves by combining the electrospinning and dip-coating methods. Scaffold morphology and mechanics were assessed, quantified and compared to native vessels. Scaffolds were seeded with Human Umbilical Vein Endothelial Cells (HUVECs), cultured in vitro for 3 days and were evaluated for cell viability and morphology. The results showed that composite scaffolds had adjustable mechanical strength and favorable biocompatibility, which is important in the future clinical application of Tissue-engineered vascular grafts (TEVGs). PMID- 26820994 TI - Nanofibrous biomimetic mesh can be used for pelvic reconstructive surgery: A randomized study. AB - BACKGROUND: Implantation of nonabsorbable polypropylene (PP) mesh in the vagina is the main surgical treatment for pelvic organ prolapse (POP); however, clinical outcomes remain controversial and far from satisfactory. In particular, reducing the exposure or erosion of vaginal implants to obtain improved functional reconstruction is challenging. There is an urgent need for the development of new materials and/or products for POP treatment. A nanofibrous biomimetic mesh was recently developed to address this issue. OBJECTIVE: In this study, the basic properties of the newly developed mesh, including structural characteristics, mechanical properties, biological response of human umbilical cord mesenchymal stem cells in vitro, and tissue regeneration and biocompatibility in vivo, were evaluated and compared with those of GynemeshTMPS. METHODS: Scanning electron microscopy and uniaxial tensile methods were used to evaluate microstructure and mechanical properties, respectively. Mesenchymal stem cell growth on the meshes was observed by fluorescence microscopy to visualize the expression of enhanced red fluorescent protein. Twenty-four mature female Sprague Dawley rats were randomly assigned to two groups: group 1 (nanofibrous biomimetic mesh, Medprin, Germany, n=12) and group 2 (Gynemesh(TM)PS, Ethicon, USA; n=12). The posterior vaginal wall was incised from the introitus, and the mesh was then implanted. Three implants of each type were tested for 1, 4, 8 and 12 weeks. Connective tissue organization, inflammation, vascularization, and regenerated tissue were histologically assessed. RESULTS: The nanofibrous biomimetic mesh is a relatively heavy material and exhibited lower porosity than Gynemesh(TM)PS. The new mesh was stiffer than Gynemesh(TM)PS (p<0.001) but supported human umbilical cord mesenchymal stem cell attachment. Erosion of the grafts did not occur in any animal. The nanofibrous biomimetic mesh was encapsulated by a thicker layer of connective tissue and was associated with significantly greater inflammatory scores compared with Gynemesh(TM)PS. At 12 weeks, the vascularization of the new mesh was greater than that of Gynemesh(TM)PS (p<0.05). No significant difference in the thickness of the smooth muscle layer following implantation was observed between the two groups (p>0.05). CONCLUSIONS: The nanofibrous biomimetic mesh is a candidate for reinforcing pelvic reconstruction. The mesh could be improved by decreasing its weight and stiffness and increasing its porosity. This mesh could serve as a carrier for stem cells in future regenerative medicine and tissue engineering research. PMID- 26820996 TI - Immunomodulating Drugs Based on Poxviral Proteins. AB - An unusually high production of cytokines or chemokines as well as increased complement activation can drive development of chronic inflammatory autoimmune diseases. State-of-the-art biological therapies, recombinant receptors, or specific antibodies that target immune and inflammatory mediators are now effectively used. However, these newer drugs are not equally effective for all patients and can cause adverse effects, making the search for new immunomodulatory proteins of great importance. The poxviruses--first and foremost, the variola (smallpox) virus, which is highly pathogenic in man--code for numerous highly evolved and extraordinarily effective immunomodulatory proteins that bind cytokines, chemokines, and proteins of the complement system. The discovery of and investigation into immune modulators from the variola virus has great potential for guiding new and effective drugs for autoimmune diseases. PMID- 26820995 TI - Is Brain Activity during Action Observation Modulated by the Perceived Fairness of the Actor? AB - Perceiving other people's actions triggers activity in premotor and parietal areas, brain areas also involved in executing and sensing our own actions. Paralleling this phenomenon, observing emotional states (including pain) in others is associated with activity in the same brain areas as activated when experiencing similar emotions directly. This emotion perception associated activity has been shown to be affected by the perceived fairness of the actor, and in-group membership more generally. Here, we examine whether action observation associated brain activity is also affected by the perceived social fairness of the actors. Perceived fairness was manipulated using an alternating iterated Prisoner's Dilemma game between the participant and two confederates, one of whom played fairly and the other unfairly. During fMRI scanning the participants watched movies of the confederates performing object-directed hand actions, and then performed hand actions themselves. Mass-univariate analysis showed that observing the actions triggered robust activation in regions associated with action execution, but failed to identify a strong modulation of this activation based on perceived fairness. Multivariate pattern analysis, however, identified clusters potentially carrying information about the perceived fairness of the actor in the middle temporal gyrus, left postcentral gyrus, right inferior parietal lobule, right middle cingulate cortex, right angular gyrus, and right superioroccipital gyrus. Despite being identified by a whole-brain searchlight analysis (and so without anatomical restriction), these clusters fall into areas frequently associated with action observation. We conclude that brain activity during action observation may be modulated by perceived fairness, but such modulation is subtle; robust activity is associated with observing the actions of both fair and unfair individuals. PMID- 26820997 TI - Expression and Purification of Neurotrophin-Elastin-Like Peptide Fusion Proteins for Neural Regeneration. AB - BACKGROUND: Neural injuries such as spinal cord injuries, traumatic brain injuries, or nerve transection injuries pose a major health problem. Neurotrophins such as nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) have been shown to improve the outcome of neural injuries in several pre-clinical models, but their use in clinics is limited by the lack of a robust delivery system that enhances their bioavailability and half-life. OBJECTIVES: We describe two fusion proteins comprising NGF or BDNF fused with elastin-like peptides (ELPs). The aim of this study was to investigate the biological activity of neurotrophin-ELP (N-ELP) fusion proteins via in vitro culture models. METHODS: NGF and BDNF were cloned in front of an elastin-like polypeptide sequence V40C2. These proteins were expressed in bacteria as inclusion bodies. These fusion proteins underwent solubilization via 8 M urea and purification via inverse transition cycling (ITC). We measured the particle size and the effect of temperature on precipitated particles using dynamic light scattering (DLS). We used western blot analysis to confirm the specificity of NGF ELP to tropomyosin receptor kinase A (TrkA) antibody and to confirm the specificity of BDNF-ELP to TrkB antibody. PC12 cells were used to perform a neurite outgrowth assay to determine the biological activity of NGF-ELP. Bioactivity of BDNF-ELP was ascertained via transfecting human epithelial kidney (HEK 293-T) cells to express the TrkB receptor. RESULTS: The proteins were successfully purified to high homogeneity by exploiting the phase transition property of ELPs and urea, which solubilize inclusion bodies. Using PC12 neurite outgrowth assay, we further demonstrated that the biological activity of NGF was retained in the fusion. Similarly, BDNF-ELP phosphorylated the TrkB receptor, suggesting the biological activity of BDNF was also retained in the fusion. We further show that owing to the phase transition property of ELPs in the fusion, these proteins self-assembled into nanoparticles at their respective transition temperatures. CONCLUSION: These fusion proteins are useful for neural regeneration, as they not only retain the biological activity of the neurotrophin but also self-assemble into nanoparticles, thereby simultaneously serving as drug delivery vehicles. These nanoparticles can serve as drug depots and will increase bioavailability by limiting neurotrophin loss due to diffusion, thereby allowing controlled spatio-temporal delivery of the neurotrophin. PMID- 26820998 TI - Quality of life in dialysis: A Malaysian perspective. AB - There is a growing interest to use quality of life as one of the dialysis outcome measurement. Based on the Malaysian National Renal Registry data on 15 participating sites, 1569 adult subjects who were alive at December 31, 2012, aged 18 years old and above were screened. Demographic and medical data of 1332 eligible subjects were collected during the administration of the short form of World Health Organization Quality of Life questionnaire (WHOQOL-BREF) in Malay, English, and Chinese language, respectively. The primary objective is to evaluate the quality of life among dialysis patients using WHOQOL-BREF. The secondary objective is to examine significant factors that affect quality of life score. Mean (SD) transformed quality of life scores were 56.2 (15.8), 59.8 (16.8), 58.2 (18.5), 59.5 (14.6), 61.0 (18.5) for (1) physical, (2) psychological, (3) social relations, (4) environment domains, and (5) combined overall quality of life and general health, respectively. Peritoneal dialysis group scored significantly higher than hemodialysis group in the mean combined overall quality of life and general health score (63.0 vs. 60.0, P < 0.001). Independent factors that were associated significantly with quality of life score in different domains include gender, body mass index, religion, education, marital status, occupation, income, mode of dialysis, hemoglobin, diabetes mellitus, coronary heart disease, cerebral vascular accident and leg amputation. Subjects on peritoneal dialysis modality achieved higher combined overall quality of life and general health score than those on hemodialysis. Religion and cerebral vascular accident were significantly associated with all domains and combined overall quality of life and general health. PMID- 26820999 TI - Dual-Mode Luminescence Modulation upon Visible-Light-Driven Photochromism with High Contrast for Inorganic Luminescence Ferroelectrics. AB - A luminescence ferroelectric oxide, Na(0.5)Bi(2.5)Nb2O9 (NBN), system with bismuth layer structure introduced by lanthanide ion (Er(3+)) has been demonstrated to exhibit reversible, high-contrast luminescence modulation (95%) and excellent fatigue resistance based on visible-light-driven photochromism (407 nm or sunlight). The coloration and decoloration process can be effectively read out by dual modes, upconversion and downshifting, and reversibly converted between green and dark gray by alternating visible light or sunlight irradiation and thermal stimulus. The luminescence modulation degree upon photochromic reactions is strongly dependent upon irradiation light wavelength and irradiation time. After undergoing several cycles, there are no significant degradations, showing high reversibility. Considering its high-contrast photoswitchable luminescence feature and intrinsic ferroelectricity of NBN host, NBN-based multifunctional materials can be suggested as a promising candidate for new potentials in photonic storage and optoelectronic multifunctional devices. PMID- 26821000 TI - Antibacterial and Synergistic Activity of Pentacyclic Triterpenoids Isolated from Alstonia scholaris. AB - (1) BACKGROUND: Alstonia scholaris (Apocynaceae) is an important medicinal plant that has been historically used in "Dai" ethnopharmacy to treat infectious diseases in China. Although various pharmacological activities have been reported, the antimicrobial constitutes of A. scholaris have not yet been identified. The objective of this study is to evaluate the antibacterial constitutes from the leaf extract of A. scholaris and to assess the synergistic effects of isolated compounds with antibiotics against bacterial pathogens.; (2) METHODS: The chemical constitutes isolated from the leaf extract of A. scholaris were structurally identified by NMR. The antibacterial and synergistic effect of compounds was assessed by calculating the minimal inhibitory concentration (MIC), checkerboard dilution test, and time-kill assay.; (3) RESULTS: Six pentacyclic triterpenoids were structurally identified as (1) lupeol, (2) betulin, (3) 3 hydroxy-11-ursen-28,13-olide, (4) betulinic acid, (5) oleanolic acid and (6) ursolic acid. Both oleanolic and ursolic acid showed antibacterial activity but were limited to Gram-positive bacteria. Ursolic acid showed a synergistic effect with ampicillin and tetracycline against both Bacillus cereus and S. aureus.; (4) CONCLUSION: These findings reflect that pentacyclic triterpenoids are the antibacterial chemicals in A. scholaris. The ability of ursolic acid to enhance the activity of antibiotics can constitute a valuable group of therapeutic agents in the future. PMID- 26821001 TI - Detecting beta-Casein Variation in Bovine Milk. AB - In bovine species, beta-casein (beta-CN) is characterized by genetic polymorphism. The two most common protein variants are beta-CN A2 (the original one) and A1, differing from A2 for one amino acid substitution (Pro67 to His67). Several bioactive peptides affecting milk nutritional properties can originate from beta-CN. Among them, beta-casomorphin-7 (BCM7) ranging from amino acid 60 to 66 can be released more easily from beta-CN variants carrying His67 (A1 type) instead of Pro67 (A2 type). Nowadays, "A2 milk" is produced in different countries claiming its potential benefits in human health. The aim of this study was to further develop and apply an isoelectric focusing electrophoresis (IEF) method to bulk and individual milk samples in order to improve its use for beta CN studies. We succeeded in identifying A2 milk samples correctly and quantifying the percentage of A2, A1, and B variants in bulk samples not derived from A2 milk as well as in individual milk samples. The method allows us to quantify the relative proportion of beta-CN variants in whole milk without eliminating whey protein by acid or enzymatic precipitation of caseins. The aim of this study was also to study the different behavior of beta-CN and beta-lactoglobulin (beta-LG) in the presence of trichloroacetic acid (TCA). The higher sensitivity of beta-CN to TCA allows quantifying beta-CN variants after TCA fixation because beta-LG is not visible. Monitoring beta-CN variation in cattle breeds is important in order to maintain a certain balance between Pro67 and His67 in dairy products. Overall, the debate between A1 and A2 milk needs further investigation. PMID- 26821002 TI - Inhibitory Effect of Crocin(s) on Lens alpha-Crystallin Glycation and Aggregation, Results in the Decrease of the Risk of Diabetic Cataract. AB - The current study investigates the inhibitory effect of crocin(s), also known as saffron apocarotenoids, on protein glycation and aggregation in diabetic rats, and alpha-crystallin glycation. Thus, crocin(s) were administered by intraperitoneal injection to normal and streptozotocin-induced diabetic rats. The cataract progression was recorded regularly every two weeks and was classified into four stages. After eight weeks, the animals were sacrificed and the parameters involved in the cataract formation were measured in the animal lenses. Some parameters were also determined in the serum and blood of the rats. In addition, the effect of crocin(s) on the structure and chaperone activity of alpha-crystallin in the presence of glucose was studied by different methods. Crocin(s) lowered serum glucose levels of diabetic rats and effectively maintained plasma total antioxidants, glutathione levels and catalase activity in the lens of the animals. In the in vitro study, crocin(s) inhibited alpha crystallin glycation and aggregation. Advanced glycation end products fluorescence, hydrophobicity and protein cross-links were also decreased in the presence of crocin(s). In addition, the decreased chaperone activity of alpha crystallin in the presence of glucose changed and became close to the native value by the addition of crocin(s) in the medium. Crocin(s) thus showed a powerful inhibitory effect on alpha-crystallin glycation and preserved the structure-function of this protein. Crocin(s) also showed the beneficial effects on prevention of diabetic cataract. PMID- 26821003 TI - Evaluation of Functionality and Biological Responses of Mytilus galloprovincialis after Exposure to Quaternium-15 (Methenamine 3-Chloroallylochloride). AB - Although the irritant effects of quaternium-15 have been established, little is known about the toxicological consequences induced by this xenobiotic on aquatic invertebrates. The present article reports toxicological, histological and physiological effects of quaternium-15 following the exposure of Mytilus galloprovincialis for 18 days at three different concentrations (0.1, 1.0 and 2.0 mg/L). The results demonstrate that at higher concentrations histological damages to M. galloprovincialis gills occur, like melanosis, light exfoliations, increase of mucus production and infiltrative inflammation. In addition digestive gland cells of M. galloprovincialis, were not able to perform the regulation volume decrease (RVD) owing to osmotic stress following the exposure to the preservative. Overall, this first study on quaternium-15 highlights that it can jeopardize both the morphology and vital physiological processes in marine invertebrates, depending on the duration of exposure and the concentration of the preservative, indicating that further studies are necessary to increase our knowledge about the effects of this substance, commonly added to our products of daily use. PMID- 26821004 TI - Synthesis and Evaluation of Aminothiazole-Paeonol Derivatives as Potential Anticancer Agents. AB - In this study, novel aminothiazole-paeonol derivatives were synthesized and characterized using 1H-NMR, (13)C-NMR, IR, mass spectroscopy, and high performance liquid chromatography. All the new synthesized compounds were evaluated according to their anticancer effect on seven cancer cell lines. The experimental results indicated that these compounds possess high anticancer potential regarding human gastric adenocarcinoma (AGS cells) and human colorectal adenocarcinoma (HT-29 cells). Among these compounds, N-[4-(2-hydroxy-4 methoxyphenyl)thiazol-2-yl]-4-methoxybenzenesulfonamide (13c) had the most potent inhibitory activity, with IC50 values of 4.0 uM to AGS, 4.4 uM to HT-29 cells and 5.8 uM to HeLa cells. The 4-fluoro-N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2 yl]benzenesulfonamide (13d) was the second potent compound, showing IC50 values of 7.2, 11.2 and 13.8 uM to AGS , HT-29 and HeLa cells, respectively. These compounds are superior to 5-fluorouracil (5-FU) for relatively higher potency against AGS and HT-29 human cancer cell lines along with lower cytotoxicity to fibroblasts. Novel aminothiazole-paeonol derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating gastrointestinal adenocarcinoma. PMID- 26821005 TI - Poly(N-4-vinylbenzyl-1,4,7-triazacyclononane) Copper Complex Grafted Solid Catalyst for Oxidative Polymerization of 2,6-Dimethylphenol. AB - A new solid phase catalyst, poly(N-4-vinylbenzyl-1,4,7-triazacyclononane) copper(I) complex, grafted onto polystyrene particles, has been employed for the oxidative polymerization of 2,6-dimethylphenol using an aqueous biphasic (water/toluene) solvent system. The solid catalyst was synthesized by first grafting N-(4-vinylbenzyl)-1,4,7-triaza-cyclononane onto polystyrene particles using a radical mediated polymerization method and next by creating the polymer metal complex of copper-triazacyclononane with these modified particles. Poly(2,6 dimethyl-1,4-phenylene oxide) was successfully obtained from the polymerization of 2,6-dimethylphenol using this new metal-organic solid phase catalyst. PMID- 26821006 TI - Coumarin-Containing Polymers for High Density Non-Linear Optical Data Storage. AB - Optical data storage was performed with various thin polymer films containing coumarin-based derivatives and by using femtosecond laser pulses as well as two photon absorption processes. Exploring the photodimerization attribute of coumarin derivatives and using appropriate irradiation wavelengths, recording/erasing processes could be carried out in the same area. Second harmonic generation microscopy was used to read the stored information. PMID- 26821007 TI - Miracle Fruit (Synsepalum dulcificum) Exhibits as a Novel Anti-Hyperuricaemia Agent. AB - Miracle fruit (Synsepalum dulcificum) belongs to the Sapotaceae family. It can change flavors on taste buds, transforming acidic tastes to sweet. We evaluated various miracle fruit extracts, including water, butanol, ethyl acetate (EA), and hexane fractions, to determine its antioxidant effects. These extracts isolated from miracle fruit exerted potential for reduction of uric acid and inhibited xanthine oxidase activity in vitro and in monosodiumurate (MSU)-treated RAW264.7 macrophages. Moreover, we also found that the butanol extracts of miracle fruit attenuated oxonic acid potassium salt-induced hyperuricaemia in ICR mice by lowering serum uric acid levels and activating hepatic xanthine oxidase. These effects were equal to those of allopurinol, suggesting that the butanol extract of miracle fruit could be developed as a novel anti-hyperuricaemia agent or health food. PMID- 26821008 TI - Imidazole Alkaloids from the South China Sea Sponge Pericharax heteroraphis and Their Cytotoxic and Antiviral Activities. AB - Marine sponges continue to serve as a rich source of alkaloids possessing interesting biological activities and often exhibiting unique structural frameworks. In the current study, chemical investigation on the marine sponge Pericharax heteroraphis collected from the South China Sea yielded one new imidazole alkaloid named naamidine J (1) along with four known ones (2-5). Their structures were established by extensive spectroscopic methods and comparison of their data with those of the related known compounds. All the isolates possessed a central 2-aminoimidazole ring, substituted by one or two functionalized benzyl groups in some combination of the C4 and C5 positions. The cytotoxicities against selected HL-60, HeLa, A549 and K562 tumor cell lines and anti-H1N1 (Influenza a virus (IAV)) activity for the isolates were evaluated. Compounds 1 and 2 exhibited cytotoxicities against the K562 cell line with IC50 values of 11.3 and 9.4 MUM, respectively. Compound 5 exhibited weak anti-H1N1 (influenza a virus, IAV) activity with an inhibition ratio of 33%. PMID- 26821009 TI - Metabolite Profiling Reveals the Effect of Dietary Rubus coreanus Vinegar on Ovariectomy-Induced Osteoporosis in a Rat Model. AB - The study was aimed at exploring the curative effects of Rubus coreanus (RC) vinegar against postmenopausal osteoporosis by using ovariectomized rats as a model. The investigations were performed in five groups: sham, ovariectomized (OVX) rats without treatment, low-dose RC vinegar (LRV)-treated OVX rats, high dose RC vinegar (HRV)-treated OVX rats and alendronate (ALEN)-treated OVX rats. The efficacy of RC vinegar was evaluated using physical, biochemical, histological and metabolomic parameters. Compared to the OVX rats, the LRV and HRV groups showed positive effects on the aforementioned parameters, indicating estrogen regulation. Plasma metabolome analysis of the groups using gas chromatography-time of flight mass spectrometry (GC-TOF-MS) and ultra-performance liquid chromatography quadrupole-TOF-MS (UPLC-Q-TOF-MS) with multivariate analysis revealed 19 and 16 metabolites, respectively. Notably, the levels of butyric acid, phenylalanine, glucose, tryptophan and some lysophosphatidylcholines were marginally increased in RC vinegar-treated groups compared to OVX. However, the pattern of metabolite levels in RC vinegar-treated groups was found similar to ALEN, but differed significantly from that in sham group. The results highlight the prophylactic and curative potential of dietary vinegar against postmenopausal osteoporosis. RC vinegar could be an effective natural alternative for the prevention of postmenopausal osteoporosis. PMID- 26821010 TI - Design of a MCoTI-Based Cyclotide with Angiotensin (1-7)-Like Activity. AB - We report for the first time the design and synthesis of a novel cyclotide able to activate the unique receptor of angiotensin (1-7) (AT1-7), the MAS1 receptor. This was accomplished by grafting an AT1-7 peptide analog onto loop 6 of cyclotide MCoTI-I using isopeptide bonds to preserve the alpha-amino and C terminal carboxylate groups of AT1-7, which are required for activity. The resulting cyclotide construct was able to adopt a cyclotide-like conformation and showed similar activity to that of AT1-7. This cyclotide also showed high stability in human serum thereby providing a promising lead compound for the design of a novel type of peptide-based in the treatment of cancer and myocardial infarction. PMID- 26821011 TI - Functional Characterization of a Dihydroflavanol 4-Reductase from the Fiber of Upland Cotton (Gossypium hirsutum). AB - Dihydroflavanol 4-reductase (DFR) is a key later enzyme involved in two polyphenols' (anthocyanins and proanthocyanidins (PAs)) biosynthesis, however it is not characterized in cotton yet. In present reports, a DFR cDNA homolog (designated as GhDFR1) was cloned from developing fibers of upland cotton. Silencing GhDFR1 in cotton by virus-induced gene silencing led to significant decrease in accumulation of anthocyanins and PAs. More interestingly, based on LC MS analysis, two PA monomers, (-)-epicatachin and (-)-epigallocatachin, remarkably decreased in content in fibers of GhDFR1-silenced plants, but two new monomers, (-)-catachin and (-)-gallocatachin were present compared to the control plants infected with empty vector. The ectopic expression of GhDFR1 in an Arabidopsis TT3 mutant allowed for reconstruction of PAs biosynthesis pathway and led to accumulation of PAs in seed coat. Taken together, these data demonstrate that GhDFR1 contributes to the biosynthesis of anthocyanins and PAs in cotton. PMID- 26821012 TI - Mesenchymal Stem Cells Preserve Working Memory in the 3xTg-AD Mouse Model of Alzheimer's Disease. AB - The transplantation of stem cells may have a therapeutic effect on the pathogenesis and progression of neurodegenerative disorders. In the present study, we transplanted human mesenchymal stem cells (MSCs) into the lateral ventricle of a triple transgenic mouse model of Alzheimer's disease (3xTg-AD) at the age of eight months. We evaluated spatial reference and working memory after MSC treatment and the possible underlying mechanisms, such as the influence of transplanted MSCs on neurogenesis in the subventricular zone (SVZ) and the expression levels of a 56 kDa oligomer of amyloid beta (Abeta*56), glutamine synthetase (GS) and glutamate transporters (Glutamate aspartate transporter (GLAST) and Glutamate transporter-1 (GLT-1)) in the entorhinal and prefrontal cortices and the hippocampus. At 14 months of age we observed the preservation of working memory in MSC-treated 3xTg-AD mice, suggesting that such preservation might be due to the protective effect of MSCs on GS levels and the considerable downregulation of Abeta*56 levels in the entorhinal cortex. These changes were observed six months after transplantation, accompanied by clusters of proliferating cells in the SVZ. Since the grafted cells did not survive for the whole experimental period, it is likely that the observed effects could have been transiently more pronounced at earlier time points than at six months after cell application. PMID- 26821013 TI - Decreased Expression of BNC1 and BNC2 Is Associated with Genetic or Epigenetic Regulation in Hepatocellular Carcinoma. AB - The aberrant expression of transcription factor Basonuclin (BNC) had been reported in different kinds of tumors. Here, we investigated the expression and methylation status of two Basonuclin homologs, BNC1 and BNC2 in hepatocellular carcinoma (HCC). We found that the expression levels of both BNC1 and BNC2 were down-regulated in HCC cell lines and primary HCC tissues. The frequency and intensity of BNC1 promoter hypermethylation in tumor tissues was significantly higher than that in adjacent non-tumor tissues. 5-Aza-2'-Deoxycytidine treatment could significantly increase the BNC1 expression in the methylated HCC cell lines, which implicated that epigenetic modification contributed to the down regulation of BNC1. In addition, BNC1 hypermethylation in tumor tissues was more likely to happen in female patients. No methylation of the BNC2 promoter was found in HCC tumor tissues. However, a frequent deletion of the BNC2 gene was observed, which indicated that the chromosomal loss of the BNC2 gene might be one important reason for its lower expression level in HCC. Our results suggested that BNC1 and BNC2 were down-regulated in HCC which may provide new insight into the tumorigenesis of HCC. PMID- 26821014 TI - Investigation of Enantioselective Membrane Permeability of alpha-Lipoic Acid in Caco-2 and MDCKII Cell. AB - alpha-Lipoic acid (LA) contains a chiral carbon and exists as two enantiomers (R alpha-lipoic acid (RLA) and S-alpha-lipoic acid (SLA)). We previously demonstrated that oral bioavailability of RLA is better than that of SLA. This difference arose from the fraction absorbed multiplied by gastrointestinal availability (F(a) * F(g)) and hepatic availability (F(h)) in the absorption phase. However, it remains unclear whether F(a) and/or F(g) are involved in enantioselectivity. In this study, Caco-2 cells and Madin-Darby canine kidney strain II cells were used to assess the enantioselectivity of membrane permeability. LA was actively transported from the apical side to basal side, regardless of the differences in its steric structure. Permeability rates were proportionally increased in the range of 10-250 ug LA/mL, and the permeability coefficient did not differ significantly between enantiomers. Hence, we conclude that enantioselective pharmacokinetics arose from the metabolism (F(h) or F(g) * F(h)), and definitely not from the membrane permeation (F(a)) in the absorption phase. PMID- 26821015 TI - Microglia-Mediated Neuroinflammation and Neurotrophic Factor-Induced Protection in the MPTP Mouse Model of Parkinson's Disease-Lessons from Transgenic Mice. AB - Parkinson's disease (PD) is a neurodegenerative disease characterised by histopathological and biochemical manifestations such as loss of midbrain dopaminergic (DA) neurons and decrease in dopamine levels accompanied by a concomitant neuroinflammatory response in the affected brain regions. Over the past decades, the use of toxin-based animal models has been crucial to elucidate disease pathophysiology, and to develop therapeutic approaches aimed to alleviate its motor symptoms. Analyses of transgenic mice deficient for cytokines, chemokine as well as neurotrophic factors and their respective receptors in the 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD have broadened the current knowledge of neuroinflammation and neurotrophic support. Here, we provide a comprehensive review that summarises the contribution of microglia-mediated neuroinflammation in MPTP-induced neurodegeneration. Moreover, we highlight the contribution of neurotrophic factors as endogenous and/or exogenous molecules to slow the progression of midbrain dopaminergic (mDA) neurons and further discuss the potential of combined therapeutic approaches employing neuroinflammation modifying agents and neurotrophic factors. PMID- 26821016 TI - Mitochondria Related Pathway Is Essential for Polysaccharides Purified from Sparassis crispa Mediated Neuro-Protection against Glutamate-Induced Toxicity in Differentiated PC12 Cells. AB - The present study aims to explore the neuro-protective effects of purified Sparassis crispa polysaccharides against L-glutamic acid (L-Glu)-induced differentiated PC12 (DPC12) cell damages and its underlying mechanisms. The Sparassis crispa water extract was purified by a DEAE-52 cellulose anion exchange column and a Sepharose G-100 column. A fraction with a molecular weight of 75 kDa and a diameter of 88.9 nm, entitled SCWEA, was obtained. SCWEA was identified with a triple helix with (1->3)-linked Rha in the backbone, and (1->2) linkages and (1->6) linkages in the side bone. Our results indicated that the pre treatment of DPC12 cells with SCWEA prior to L-Glu exposure effectively reversed the reduction on cell viability (by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay) and reduced L-Glu-induced apoptosis (by Hoechst staining). SCWEA decreased the accumulation of intracellular reactive oxygen species, blocked Ca(2+) influx and prevented depolarization of the mitochondrial membrane potential in DPC12 cells. Furthermore, SCWEA normalized expression of anti-apoptotic proteins in L-Glu-explored DPC12 cells. These results suggested that SCWEA protects against L-Glu-induced neuronal apoptosis in DPC12 cells and may be a promising candidate for treatment against neurodegenerative disease. PMID- 26821018 TI - miR-16-5p Is a Stably-Expressed Housekeeping MicroRNA in Breast Cancer Tissues from Primary Tumors and from Metastatic Sites. AB - For quantitative microRNA analyses in formalin-fixed paraffin-embedded (FFPE) tissue, expression levels have to be normalized to endogenous controls. To investigate the most stably-expressed microRNAs in breast cancer and its surrounding tissue, we used tumor samples from primary tumors and from metastatic sites. MiRNA profiling using TaqMan((r)) Array Human MicroRNA Cards, enabling quantification of 754 unique human miRNAs, was performed in FFPE specimens from 58 patients with metastatic breast cancer. Forty-two (72%) samples were collected from primary tumors and 16 (28%) from metastases. In a cross-platform analysis of a validation cohort of 32 FFPE samples from patients with early breast cancer genome-wide microRNA expression analysis using SurePrintG3 miRNA (8 * 60 K)((r)) microarrays from Agilent((r)) was performed. Eleven microRNAs could be detected in all samples analyzed. Based on NormFinder and geNorm stability values and the high correlation (rho >= 0.8) with the median of all measured microRNAs, miR-16 5p, miR-29a-3p, miR-126-3p, and miR-222-3p are suitable single gene housekeeper candidates. In the cross-platform validation, 29 human microRNAs were strongly expressed (mean log2-intensity > 10) and 21 of these microRNAs including miR-16 5p and miR-29a-3p were also stably expressed (CV < 5%). Thus, miR-16-5p and miR 29a-3p are both strong housekeeper candidates. Their Normfinder stability values calculated across the primary tumor and metastases subgroup indicate that miR-29a 3p can be considered as the strongest housekeeper in a cohort with mainly samples from primary tumors, whereas miR-16-5p might perform better in a metastatic sample enriched cohort. PMID- 26821019 TI - Identification and Characterization of MicroRNAs in Snakehead Fish Cell Line upon Snakehead Fish Vesiculovirus Infection. AB - MicroRNAs (miRNAs) play important roles in mediating multiple biological processes in eukaryotes and are being increasingly studied to evaluate their roles associated with cellular changes following viral infection. Snakehead fish Vesiculovirus (SHVV) has caused mass mortality in snakehead fish during the past few years. To identify specific miRNAs involved in SHVV infection, we performed microRNA deep sequencing on a snakehead fish cell line (SSN-1) with or without SHVV infection. A total of 205 known miRNAs were identified when they were aligned with the known zebrafish miRNAs, and nine novel miRNAs were identified using MiRDeep2 software. Eighteen and 143 of the 205 known miRNAs were differentially expressed at three and 24 h post-infection (poi), respectively. From the differentially-expressed miRNAs, five were randomly selected to validate their expression profiles using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and their expression profiles were consistent with the microRNA sequencing results. In addition, the target gene prediction of the SHVV genome was performed for the differentially-expressed host miRNAs, and a total of 10 and 58 differentially-expressed miRNAs were predicted to bind to the SHVV genome at three and 24 h poi, respectively. The effects of three selected miRNAs (miR-130-5p, miR-214 and miR-216b) on SHVV multiplication were evaluated using their mimics and inhibitors via qRT-PCR and Western blotting. The results showed that all three miRNAs were able to inhibit the multiplication of SHVV; whereas the mechanisms underlying the SHVV multiplication inhibited by the specific miRNAs need to be further characterized in the future. PMID- 26821022 TI - On the Use of Monopole Antennas for Determining the Effect of the Enclosure of a Power Transformer Tank in Partial Discharges Electromagnetic Propagation. AB - A well-defined condition-monitoring for power transformers is key to implementing a correct condition-based maintenance (CBM). In this regard, partial discharges (PD) measurement and its analysis allows to carry out on-line maintenance following the standards IEC-60270 and IEC-60076. However, new PD measurements techniques, such as acoustics or electromagnetic (EM) acquisitions using ultra high-frequency (UHF) sensors are being taken into account, IEC-62478. PD measurements with antennas and the effect of their EM propagation in power transformer tanks is an open research topic that is considered in this paper. In this sense, an empty tank model is studied as a rectangular cavity and their resonances are calculated and compared with their measurement with a network analyser. Besides, two low cost improved monopole antennas deployed inside and outside of the tank model capture background noise and PD pulses in three different test objects (Nomex, twisted pair and insulator). The average spectrum of them are compared and can be found that mainly, the antenna frequency response, the frequency content distribution depending on the PD source and the enclosure resonances modes are the main factors to be considered in PD acquisitions with these sensors. Finally, with this set-up, it is possible to measure PD activity inside the tank from outside. PMID- 26821020 TI - ERalpha Mediates Estrogen-Induced Expression of the Breast Cancer Metastasis Suppressor Gene BRMS1. AB - Recently, estrogen has been reported as putatively inhibiting cancer cell invasion and motility. This information is in direct contrast to the paradigm of estrogen as a tumor promoter. However, data suggests that the effects of estrogen are modulated by the receptor isoform with which it interacts. In order to gain a clearer understanding of the role of estrogen in potentially suppressing breast cancer metastasis, we investigated the regulation of estrogen and its receptor on the downstream target gene, breast cancer metastasis suppressor 1 (BRMS1) in MCF 7, SKBR3, TTU-1 and MDA-MB-231 breast cancer cells. Our results showed that estrogen increased the transcription and expression of BRMS1 in the ERalpha positive breast cancer cell line, MCF-7. Additionally, the ERalpha specific agonist PPT also induced the transcription and expression of BRMS1. However, the two remaining estrogen receptor (ER) subtype agonists had no effect on BRMS1 expression. In order to further examine the influence of ERalpha on BRMS1 expression, ERalpha expression was knocked down using siRNA (siERalpha). Western blot analysis showed that siERalpha reduced estrogen-induced and PPT-induced BRMS1 expression. In summary, this study demonstrates estrogen, via its alpha receptor, positively regulates the expression of BRMS1, providing new insight into a potential inhibitory effect of estrogen on metastasis suppression. PMID- 26821017 TI - Insights into Protein-Ligand Interactions: Mechanisms, Models, and Methods. AB - Molecular recognition, which is the process of biological macromolecules interacting with each other or various small molecules with a high specificity and affinity to form a specific complex, constitutes the basis of all processes in living organisms. Proteins, an important class of biological macromolecules, realize their functions through binding to themselves or other molecules. A detailed understanding of the protein-ligand interactions is therefore central to understanding biology at the molecular level. Moreover, knowledge of the mechanisms responsible for the protein-ligand recognition and binding will also facilitate the discovery, design, and development of drugs. In the present review, first, the physicochemical mechanisms underlying protein-ligand binding, including the binding kinetics, thermodynamic concepts and relationships, and binding driving forces, are introduced and rationalized. Next, three currently existing protein-ligand binding models--the "lock-and-key", "induced fit", and "conformational selection"--are described and their underlying thermodynamic mechanisms are discussed. Finally, the methods available for investigating protein-ligand binding affinity, including experimental and theoretical/computational approaches, are introduced, and their advantages, disadvantages, and challenges are discussed. PMID- 26821021 TI - Subchronic Exposure to Arsenic Represses the TH/TRbeta1-CaMK IV Signaling Pathway in Mouse Cerebellum. AB - We previously reported that arsenic (As) impaired learning and memory by down regulating calmodulin-dependent protein kinase IV (CaMK IV) in mouse cerebellum. It has been documented that the thyroid hormone receptor (TR)/retinoid X receptor (RXR) heterodimer and thyroid hormone (TH) may be involved in the regulation of CaMK IV. To investigate whether As affects the TR/RXR heterodimer and TH, we determined As concentration in serum and cerebellum, 3,5,3'-triiodothyronine (T3) and thyroxin (T4) levels in serum, and expression of CaMK IV, TR and RXR in cerebellum of mice exposed to As. Cognition function was examined by the step down passive avoidance task and Morris water maze (MWM) tests. Morphology of the cerebellum was observed by Hematoxylin-Eosin staining under light microscope. Our results showed that the concentrations of As in the serum and cerebellum of mice both increased with increasing As-exposure level. A significant positive correlation was found between the two processes. Adeficit in learning and memory was found in the exposed mice. Abnormal morphologic changes of Purkinje cells were observed in cerebellum of the exposed mice. Moreover, the cerebellar expressions of CaMK IV protein and the TRbeta gene, and TRbeta1 protein were significantly lower in As-exposed mice than those in controls. Subchronic exposure to As appears to increase its level in serum and cerebella of mice, impairing learning and memory and down-regulating expression of TRbeta1 as well as down-stream CaMK IV. It is also suggested that the increased As may be responsible for down-regulation of TRbeta1 and CaMK IV in cerebellum and that the down-regulated TRbeta1 may be involved in As-induced impairment of learning and memory via inhibiting CaMK IV and its down-stream pathway. PMID- 26821023 TI - Multi-Channel Capacitive Sensor Arrays. AB - In this paper, multi-channel capacitive sensor arrays based on microstrip band stop filters are studied. The sensor arrays can be used to detect the proximity of objects at different positions and directions. Each capacitive sensing structure in the array is connected to an inductive element to form resonance at different frequencies. The resonances are designed to be isolated in the frequency spectrum, such that the change in one channel does not affect resonances at other channels. The inductive element associated with each capacitive sensor can be surface-mounted inductors, integrated microstrip inductors or metamaterial-inspired structures. We show that by using metamaterial split-ring structures coupled to a microstrip line, the quality factor of each resonance can be greatly improved compared to conventional surface-mounted or microstrip meander inductors. With such a microstrip-coupled split-ring design, more sensing elements can be integrated in the same frequency spectrum, and the sensitivity can be greatly improved. PMID- 26821024 TI - Improved Circuits with Capacitive Feedback for Readout Resistive Sensor Arrays. AB - One of the most suitable ways of distributing a resistive sensor array for reading is an array with M rows and N columns. This allows reduced wiring and a certain degree of parallelism in the implementation, although it also introduces crosstalk effects. Several types of circuits can carry out the analogue-digital conversion of this type of sensors. This article focuses on the use of operational amplifiers with capacitive feedback and FPGAs for this task. Specifically, modifications of a previously reported circuit are proposed to reduce the errors due to the non-idealities of the amplifiers and the I/O drivers of the FPGA. Moreover, calibration algorithms are derived from the analysis of the proposed circuitry to reduce the crosstalk error and improve the accuracy. Finally, the performances of the proposals is evaluated experimentally on an array of resistors and for different ranges. PMID- 26821025 TI - 3D Markov Process for Traffic Flow Prediction in Real-Time. AB - Recently, the correct estimation of traffic flow has begun to be considered an essential component in intelligent transportation systems. In this paper, a new statistical method to predict traffic flows using time series analyses and geometric correlations is proposed. The novelty of the proposed method is two fold: (1) a 3D heat map is designed to describe the traffic conditions between roads, which can effectively represent the correlations between spatially- and temporally-adjacent traffic states; and (2) the relationship between the adjacent roads on the spatiotemporal domain is represented by cliques in MRF and the clique parameters are obtained by example-based learning. In order to assess the validity of the proposed method, it is tested using data from expressway traffic that are provided by the Korean Expressway Corporation, and the performance of the proposed method is compared with existing approaches. The results demonstrate that the proposed method can predict traffic conditions with an accuracy of 85%, and this accuracy can be improved further. PMID- 26821027 TI - Assessing the Performance of Sensor Fusion Methods: Application to Magnetic Inertial-Based Human Body Tracking. AB - Information from complementary and redundant sensors are often combined within sensor fusion algorithms to obtain a single accurate observation of the system at hand. However, measurements from each sensor are characterized by uncertainties. When multiple data are fused, it is often unclear how all these uncertainties interact and influence the overall performance of the sensor fusion algorithm. To address this issue, a benchmarking procedure is presented, where simulated and real data are combined in different scenarios in order to quantify how each sensor's uncertainties influence the accuracy of the final result. The proposed procedure was applied to the estimation of the pelvis orientation using a waist worn magnetic-inertial measurement unit. Ground-truth data were obtained from a stereophotogrammetric system and used to obtain simulated data. Two Kalman-based sensor fusion algorithms were submitted to the proposed benchmarking procedure. For the considered application, gyroscope uncertainties proved to be the main error source in orientation estimation accuracy for both tested algorithms. Moreover, although different performances were obtained using simulated data, these differences became negligible when real data were considered. The outcome of this evaluation may be useful both to improve the design of new sensor fusion methods and to drive the algorithm tuning process. PMID- 26821028 TI - The Local Integrity Approach for Urban Contexts: Definition and Vehicular Experimental Assessment. AB - A novel cooperative integrity monitoring concept, called "local integrity", suitable to automotive applications in urban scenarios, is discussed in this paper. The idea is to take advantage of a collaborative Vehicular Ad hoc NETwork (VANET) architecture in order to perform a spatial/temporal characterization of possible degradations of Global Navigation Satellite System (GNSS) signals. Such characterization enables the computation of the so-called "Local Protection Levels", taking into account local impairments to the received signals. Starting from theoretical concepts, this paper describes the experimental validation by means of a measurement campaign and the real-time implementation of the algorithm on a vehicular prototype. A live demonstration in a real scenario has been successfully carried out, highlighting effectiveness and performance of the proposed approach. PMID- 26821029 TI - High-Accuracy, Compact Scanning Method and Circuit for Resistive Sensor Arrays. AB - The zero-potential scanning circuit is widely used as read-out circuit for resistive sensor arrays because it removes a well known problem: crosstalk current. The zero-potential scanning circuit can be divided into two groups based on type of row drivers. One type is a row driver using digital buffers. It can be easily implemented because of its simple structure, but we found that it can cause a large read-out error which originates from on-resistance of the digital buffers used in the row driver. The other type is a row driver composed of operational amplifiers. It, very accurately, reads the sensor resistance, but it uses a large number of operational amplifiers to drive rows of the sensor array; therefore, it severely increases the power consumption, cost, and system complexity. To resolve the inaccuracy or high complexity problems founded in those previous circuits, we propose a new row driver which uses only one operational amplifier to drive all rows of a sensor array with high accuracy. The measurement results with the proposed circuit to drive a 4 * 4 resistor array show that the maximum error is only 0.1% which is remarkably reduced from 30.7% of the previous counterpart. PMID- 26821026 TI - Evaluation of the Bitterness of Traditional Chinese Medicines using an E-Tongue Coupled with a Robust Partial Least Squares Regression Method. AB - To accurately, safely, and efficiently evaluate the bitterness of Traditional Chinese Medicines (TCMs), a robust predictor was developed using robust partial least squares (RPLS) regression method based on data obtained from an electronic tongue (e-tongue) system. The data quality was verified by the Grubb's test. Moreover, potential outliers were detected based on both the standardized residual and score distance calculated for each sample. The performance of RPLS on the dataset before and after outlier detection was compared to other state-of the-art methods including multivariate linear regression, least squares support vector machine, and the plain partial least squares regression. Both R2 and root mean-squares error (RMSE) of cross-validation (CV) were recorded for each model. With four latent variables, a robust RMSECV value of 0.3916 with bitterness values ranging from 0.63 to 4.78 were obtained for the RPLS model that was constructed based on the dataset including outliers. Meanwhile, the RMSECV, which was calculated using the models constructed by other methods, was larger than that of the RPLS model. After six outliers were excluded, the performance of all benchmark methods markedly improved, but the difference between the RPLS model constructed before and after outlier exclusion was negligible. In conclusion, the bitterness of TCM decoctions can be accurately evaluated with the RPLS model constructed using e-tongue data. PMID- 26821030 TI - Spectral Similarity Assessment Based on a Spectrum Reflectance-Absorption Index and Simplified Curve Patterns for Hyperspectral Remote Sensing. AB - Hyperspectral images possess properties such as rich spectral information, narrow bandwidth, and large numbers of bands. Finding effective methods to retrieve land features from an image by using similarity assessment indices with specific spectral characteristics is an important research question. This paper reports a novel hyperspectral image similarity assessment index based on spectral curve patterns and a reflection-absorption index. First, some spectral reflection absorption features are extracted to restrict the subsequent curve simplification. Then, the improved Douglas-Peucker algorithm is employed to simplify all spectral curves without setting the thresholds. Finally, the simplified curves with the feature points are matched, and the similarities among the spectral curves are calculated using the matched points. The Airborne Visible Infrared Imaging Spectrometer (AVIRIS) and Reflective Optics System Imaging Spectrometer (ROSIS) hyperspectral image datasets are then selected to test the effect of the proposed index. The practical experiments indicate that the proposed index can achieve higher precision and fewer points than the traditional spectral information divergence and spectral angle match. PMID- 26821031 TI - Laterally Driven Resonant Pressure Sensor with Etched Silicon Dual Diaphragms and Combined Beams. AB - A novel structure of the resonant pressure sensor is presented in this paper, which tactfully employs intercoupling between dual pressure-sensing diaphragms and a laterally driven resonant strain gauge. After the resonant pressure sensor principle is introduced, the coupling mechanism of the diaphragms and resonator is analyzed and the frequency equation of the resonator based on the triangle geometry theory is developed for this new coupling structure. The finite element (FE) simulation results match the theoretical analysis over the full scale of the device. This pressure sensor was first fabricated by dry/wet etching and thermal silicon bonding, followed by vacuum-packaging using anodic bonding technology. The test maximum error of the fabricated sensor is 0.0310%F.S. (full scale) in the range of 30 to 190 kPa, its pressure sensitivity is negative and exceeding 8 Hz/kPa, and its Q-factor reaches 20,000 after wafer vacuum-packaging. A novel resonant pressure sensor with high accuracy is presented in this paper. PMID- 26821032 TI - Larvicidal Potential of the Halogenated Sesquiterpene (+)-Obtusol, Isolated from the Alga Laurencia dendroidea J. Agardh (Ceramiales: Rhodomelaceae), against the Dengue Vector Mosquito Aedes aegypti (Linnaeus) (Diptera: Culicidae). AB - Dengue is considered a serious public health problem in many tropical regions of the world including Brazil. At the moment, there is no viable alternative to reduce dengue infections other than controlling the insect vector, Aedes aegypti Linnaeus. In the continuing search for new sources of chemicals targeted at vector control, natural products are a promising alternative to synthetic pesticides. In our work, we investigated the toxicity of a bioactive compound extracted from the red alga Laurencia dendroidea J. Agardh. The initial results demonstrated that crude extracts, at a concentration of 5 ppm, caused pronounced mortality of second instar A. aegypti larvae. Two molecules, identified as (-) elatol and (+)-obtusol were subsequently isolated from crude extract and further evaluated. Assays with (-)-elatol showed moderate larvicidal activity, whereas (+)-obtusol presented higher toxic activity than (-)-elatol, with a LC50 value of 3.5 ppm. Histological analysis of the larvae exposed to (+)-obtusol revealed damage to the intestinal epithelium. Moreover, (+)-obtusol-treated larvae incubated with 2 uM CM-H2DCFDA showed the presence of reactive oxygen species, leading us to suggest that epithelial damage might be related to redox imbalance. These results demonstrate the potential of (+)-obtusol as a larvicide for use against A. aegypti and the possible mode of action of this compound. PMID- 26821033 TI - New Perspectives in the Chemistry of Marine Pyridoacridine Alkaloids. AB - Secondary metabolites from marine organisms are a rich source of novel leads for drug development. Among these natural products, polycyclic aromatic alkaloids of the pyridoacridine type have attracted the highest attention as lead compounds for the development of novel anti-cancer and anti-infective drugs. Numerous sophisticated total syntheses of pyridoacridine alkaloids have been worked out, and many of them have also been extended to the synthesis of libraries of analogues of the alkaloids. This review summarizes the progress in the chemistry of pyridoacridine alkaloids that was made in the last one-and-a-half decades. PMID- 26821035 TI - Smoke-Free Public Policies and Voluntary Policies in Personal Settings in Tbilisi, Georgia: A Qualitative Study. AB - Georgia has limited tobacco control policies, particularly in the area of smoke free public policies, which may influence the adoption of smoke-free home rules. We qualitatively examined knowledge about and reactions to public and personal smoke-free policies among Tbilisi residents. In Spring 2014, we conducted six focus groups among 47 total participants--two among male smokers, one among male nonsmokers, two among female smokers, and one among female nonsmokers. Our sample was 48.9% male and 70.2% past 30-day smokers. Most believed that SHS was dangerous, with particular concern regarding the impact of SHS on children and pregnant women. Many had misconceptions about how to protect others from SHS and the effectiveness of some approaches. Many indicated that they had some type of home rules, but few reported a complete ban on smoking in the home. Even when some restrictions were in place, they rarely were effective or enforced. Common concerns about the partial smoke-free public policy in Georgia included its economic impact, perceived discrimination among smokers, and the policy being against the Georgian culture. These concerns were heightened when participants were asked about the possible implementation of a complete smoke-free policy. Educational programs are needed to promote smoke-free policies in Georgia. PMID- 26821036 TI - Association Between Smoking and Physician-Diagnosed Stroke and Myocardial Infarction in Male Adults in Korea. AB - To evaluate the association between smoking and physician-diagnosed stroke and myocardial infarction, this study used Community Health Survey data from 2009 on 92,082 males over the age of 30 years. Using multiple logistic regression, association index between smoking and physician-diagnosed stroke and myocardial infarction was calculated after adjusting the effects of age, hypertension, and diabetes. The odds ratios (95% confidence interval) of the physician-diagnosed stroke and myocardial infarction in the smoking group were 1.12 (1.02-1.24) and 1.21 (1.06-1.38) compared to the non-smoking group. The values of the physician diagnosed stroke and myocardial infarction were 0.84 (0.74-0.94) and 0.96 (0.82 1.12) in the current-smoking subgroup, 1.38 (1.24-1.53) and 1.45 (1.26-1.67) in the ex-smoking subgroup, 1.39 (1.18-1.63) and 1.85 (1.53-2.24) in the 10- to 19 year smokers groups, 1.39 (1.22-1.58) and 1.36 (1.15-1.60) in the 30- to 40-year smokers groups, and 0.53 (0.44-0.63) and 0.47 (0.36-0.63) in those who had smoked for over 50 years. These results showed smoking was a risk factor for stroke and myocardial infarction in Korean males. This objective evidence should guide policy-making and public health interventions in the fields of smoking prevention and prohibition. PMID- 26821037 TI - A Bicycle-Based Field Measurement System for the Study of Thermal Exposure in Cuyahoga County, Ohio, USA. AB - Collecting a fine scale of microclimate data can help to determine how physical characteristics (e.g., solar radiation, albedo, sky view factor, vegetation) contribute to human exposure to ground and air temperatures. These data also suggest how urban design strategies can reduce the negative impacts of the urban heat island effect. However, urban microclimate measurement poses substantial challenges. For example, data taken at local airports are not representative of the conditions at the neighborhood or district level because of variation in impervious surfaces, vegetation, and waste heat from vehicles and buildings. In addition, fixed weather stations cannot be deployed quickly to capture data from a heat wave. While remote sensing can provide data on land cover and ground surface temperatures, resolution and cost remain significant limitations. This paper describes the design and validation of a mobile measurement bicycle. This bicycle permits movement from space to space within a city to assess the physical and thermal properties of microclimates. The construction of the vehicle builds on investigations of the indoor thermal environment of buildings using thermal comfort carts. PMID- 26821034 TI - Strategies to Maximize the Potential of Marine Biomaterials as a Platform for Cell Therapy. AB - Marine biopolymers have been explored as a promising cell therapy system for efficient cell delivery and tissue engineering. However, the marine biomaterial based systems themselves have exhibited limited performance in terms of maintenance of cell viability and functions, promotion of cell proliferation and differentiation as well as cell delivery efficiency. Thus, numerous novel strategies have been devised to improve cell therapy outcomes. The strategies include optimization of physical and biochemical properties, provision of stimuli responsive functions, and design of platforms for efficient cell delivery and tissue engineering. These approaches have demonstrated substantial improvement of therapeutic outcomes in a variety of research settings. In this review, therefore, research progress made with marine biomaterials as a platform for cell therapy is reported along with current research directions to further advance cell therapies as a tool to cure incurable diseases. PMID- 26821038 TI - Factors Associated with Complete Home Smoking Ban among Chinese Parents of Young Children. AB - (1) BACKGROUND: The home environment is a major source of Environmental Tobacco Smoke (ETS) exposure among children especially in early childhood. ETS exposure is an important health risk among children and can cause severe and chronic diseases, such as asthma, bronchitis, and premature death. However, ETS exposure at home has often been neglected in the Chinese families. Identification of factors that facilitate or otherwise hamper the adoption of home smoking ban will help in the design and implementation of evidence-based intervention programs. This study identifies factors correlated with home smoking bans in Chinese families with children. (2) METHODS: A cross-sectional survey of parents living in Nanning city, Guangxi Province, China with at least one smoker and a child in the household was conducted between September, 2013 and January, 2014. A Chi square test was used to compare categorical variables differences between the parents who had home smoking bans and those with no home smoking ban. Multiple logistic regression analyses were used to identify factors correlated with home smoking bans. (3) RESULTS: 969 completed questionnaires were collected with a response rate of 92.29% (969/1050). Of the respondents (n = 969), 14.34% had complete home smoking bans. Factors that were associated with home smoking bans were: having no other smokers in the family (OR = 2.173), attaining education up to high school (OR = 2.471), believing that paternal smoking would increase the risk of lower respiratory tract illnesses (OR = 2.755), perceiving the fact that smoking cigarettes in the presence of the child will hurt the child's health (OR = 1.547), believing that adopting a no smoking policy at home is very important (OR = 2.816), and being confident to prevent others to smoke at home (OR = 1.950). Additionally, parents who perceived difficulty in adopting a no smoking policy at home would not have a home smoking ban (OR = 0.523). (4) CONCLUSIONS: A home smoking ban is not widely adopted by families of hospitalized children in Guangxi Province, China. To protect the health of children, there is a need to develop and test interventions to promote home smoking bans. Factors identified as predictors of home smoking ban should be considered in the design of interventions. PMID- 26821039 TI - Assessing the Environmental and Socio-Economic Impacts of Artisanal Gold Mining on the Livelihoods of Communities in the Tarkwa Nsuaem Municipality in Ghana. AB - Gold mining has played an important role in Ghana's economy, however the negative environmental and socio-economic effects on the host communities associated with gold mining have overshadowed these economic gains. It is within this context that this paper assessed in an integrated manner the environmental and socio economic impacts of artisanal gold mining in the Tarkwa Nsuaem Municipality from a natural and social science perspective. The natural science group collected 200 random samples on bi-weekly basis between January to October 2013 from water bodies in the study area for analysis in line with methods outlined by the American Water Works Association, while the social science team interviewed 250 residents randomly selected for interviews on socio-economic issues associated with mining. Data from the socio-economic survey was analyzed using logistic regression with SPSS version 17. The results of the natural science investigation revealed that the levels of heavy metals in water samples from the study area in most cases exceeded GS 175-1/WHO permissible guideline values, which are in tandem with the results of inhabitants' perceptions of water quality survey (as 83% of the respondents are of the view that water bodies in the study area are polluted). This calls for cost-benefits analysis of mining before new mining leases are granted by the relevant authorities. PMID- 26821040 TI - Divergent Effects of Arsenic on NF-kappaB Signaling in Different Cells or Tissues: A Systematic Review and Meta-Analysis. AB - Arsenic is ubiquitously present in human lives, including in the environment and organisms, and has divergent effects between different cells and tissues and between different exposure times and doses. These observed effects have been attributed to the nuclear transcription factor kappa B(NF-kappaB) signaling pathway. Herein, a meta-analysis was performed by independently searching databases including the Cochrane Library, PubMed, Springer, Embase, and China National Knowledge Infrastructure, to analyze effects of arsenic exposure on NF kappaB signaling. Compared to controls, in the exposed group, p-IkappaB levels were found to be 8.13-fold higher (95% CI, 2.40-13.85; Z = 2.78; p = 0.005), IkappaB levels were 16.19-fold lower (95% CI, -27.44--4.94; Z = 2.78; p = 0.005), and NF-kappaBp65 levels were 0.77-fold higher (95% CI, 0.13-1.42; Z = 2.34; p = 0.02) for normal cells and tissue, while NF-kappaBp65 levels were 4.90-fold lower (95% CI, -8.49-1.31; Z = 2.62; p = 0.009), NF-kappaB activity was 2.45-fold lower (95% CI, -3.66-1.25; Z = 4.00; p < 0.0001), and DNA-binding activity of NF-kappaB was 9.75-fold lower (95% CI, -18.66-4.54; Z = 2.15; p = 0.03) for abnormal cells and tissue. Short exposure to high arsenic doses activated the NF-kappaB signaling pathway, while long exposure to low arsenic doses suppressed NF-kappaB signaling pathway activation. These findings may provide a theoretical basis for injurious and therapeutic mechanisms of divergent effects of arsenic. PMID- 26821041 TI - HPV Population Profiling in Healthy Men by Next-Generation Deep Sequencing Coupled with HPV-QUEST. AB - Multiple-type human papillomaviruses (HPV) infection presents a greater risk for persistence in asymptomatic individuals and may accelerate cancer development. To extend the scope of HPV types defined by probe-based assays, multiplexing deep sequencing of HPV L1, coupled with an HPV-QUEST genotyping server and a bioinformatic pipeline, was established and applied to survey the diversity of HPV genotypes among a subset of healthy men from the HPV in Men (HIM) Multinational Study. Twenty-one HPV genotypes (12 high-risk and 9 low-risk) were detected in the genital area from 18 asymptomatic individuals. A single HPV type, either HPV16, HPV6b or HPV83, was detected in 7 individuals, while coinfection by 2 to 5 high-risk and/or low-risk genotypes was identified in the other 11 participants. In two individuals studied for over one year, HPV16 persisted, while fluctuations of coinfecting genotypes occurred. HPV L1 regions were generally identical between query and reference sequences, although nonsynonymous and synonymous nucleotide polymorphisms of HPV16, 18, 31, 35h, 59, 70, 73, cand85, 6b, 62, 81, 83, cand89 or JEB2 L1 genotypes, mostly unidentified by linear array, were evident. Deep sequencing coupled with HPV-QUEST provides efficient and unambiguous classification of HPV genotypes in multiple-type HPV infection in host ecosystems. PMID- 26821042 TI - Effects of Dietary Protein Source and Quantity during Weight Loss on Appetite, Energy Expenditure, and Cardio-Metabolic Responses. AB - Higher protein meals increase satiety and the thermic effect of feeding (TEF) in acute settings, but it is unclear whether these effects remain after a person becomes acclimated to energy restriction or a given protein intake. This study assessed the effects of predominant protein source (omnivorous, beef/pork vs. lacto-ovo vegetarian, soy/legume) and quantity (10%, 20%, or 30% of energy from protein) on appetite, energy expenditure, and cardio-metabolic indices during energy restriction (ER) in overweight and obese adults. Subjects were randomly assigned to one protein source and then consumed diets with different quantities of protein (4 weeks each) in a randomized crossover manner. Perceived appetite ratings (free-living and in-lab), TEF, and fasting cardio-metabolic indices were assessed at the end of each 4-week period. Protein source and quantity did not affect TEF, hunger, or desire to eat, other than a modestly higher daily composite fullness rating with 30% vs. 10% protein diet (p = 0.03). While the 20% and 30% protein diets reduced cholesterol, triacylglycerol, and APO-B vs. 10% protein (p < 0.05), protein source did not affect cardio-metabolic indices. In conclusion, diets varying in protein quantity with either beef/pork or soy/legume as the predominant source have minimal effects on appetite control, energy expenditure and cardio-metabolic risk factors during ER-induced weight loss. PMID- 26821043 TI - Correction: McLean, R., Edmonds, J., Williams, S., Mann, J., Skeaff, S. Balancing Sodium and Potassium: Estimates of Intake in a New Zealand Adult Population Sample. Nutrients 2015, 7(11), 8930-8938. PMID- 26821044 TI - Impact of Food Rations and Supplements on Micronutrient Status by Trimester of Pregnancy: Cross-Sectional Studies in the Maela Refugee Camp in Thailand. AB - Micronutrient fortified flour (MFF), supplementary food rations and micronutrient (MN) supplements may prevent deficiencies among pregnant women. Objectives of cross-sectional surveys in 2004 (n = 533) and 2006 (n = 515) were to assess the impact of new food rations (flour, oil) and supplements on MN status by trimester of pregnancy in the Maela refugee camp. Hemoglobin, iron status, zinc, retinol, beta-carotene and tryptophan decreased, while alpha-/gamma-tocopherol and 5 methyltetrahydrofolate (5-MTHF) increased from first to third trimester. In 2006, mean zinc and alpha-tocopherol for each trimester was significantly higher than in 2004. The weeks of supplemented thiamine and folic acid were positively correlated with thiamine diphosphate (TDP) and 5-MTHF, but not for ferrous sulfate as iron deficiency was observed in 38.5% of third-trimester women. Frequent consumption of fish paste and owning a garden or animal were associated with significantly higher iron status, retinol, beta-carotene, and 5-MTHF. In conclusion, MFF and supplementary oil were most likely to explain improved zinc and alpha-tocopherol status, while thiamine and folate supplements ensured high TDP and 5-MTHF in late pregnancy. MN supplements, MN-rich staple food, small gardens, and programs to improve iron compliance are promising strategies to prevent MN deficiencies during pregnancy in vulnerable populations. PMID- 26821045 TI - Effects of Oral Exposure Duration and Gastric Energy Content on Appetite Ratings and Energy Intake in Lean Men. AB - Studies show that longer oral exposure to food leads to earlier satiation and lowers energy intake. Moreover, higher energy content of food has been shown to lead to higher satiety. Up to now, it has not been studied systematically how oral exposure duration and gastric energy content interact in satiety regulation. Thirty-seven men (22 +/- 4 years, 22 +/- 2 kg/m2) participated in a randomized cross-over trial, in which we independently manipulated: (1) oral exposure duration by modified sham feeding (MSF) for 1 or 8 min; and (2) energy content of gastric load (GL) by a nasogastric tube: 100 kcal/500 mL or 700 kcal/500 mL. Outcome measures were appetite ratings and subsequent energy intake from an ad libitum meal. Energy intake was 35% lower after the GLs with 700 kcal than with 100 kcal (p < 0.0001). All appetite ratings were lower in the 700 kcal than in the 100 kcal treatments (area under the curve (AUC); p-values <= 0.002); fullness was higher and prospective consumption was lower in the 8 min than in the 1 min MSF treatments (AUC; p-values <= 0.02). In conclusion, the current showed that a GL of 700 kcal/500 mL vs. 100 kcal/500 mL increased satiety and lowered energy intake. No additional effects of oral exposure duration could be observed, presumably due to the high contrast in energy between the manipulations. Future research should also focus on the role of oral exposure as such and not only the duration. PMID- 26821047 TI - The Complete Genome of Brucella Suis 019 Provides Insights on Cross-Species Infection. AB - Brucella species are the most important zoonotic pathogens worldwide and cause considerable harm to humans and animals. In this study, we presented the complete genome of B. suis 019 isolated from sheep (ovine) with epididymitis. B. suis 019 has a rough phenotype and can infect sheep, rhesus monkeys and possibly humans. The comparative genome analysis demonstrated that B. suis 019 is closest to the vaccine strain B. suis bv. 1 str. S2. Further analysis associated the rsh gene to the pathogenicity of B. suis 019, and the WbkA gene to the rough phenotype of B. suis 019. The 019 complete genome data was deposited in the GenBank database with ID PRJNA308608. PMID- 26821046 TI - Feedback Regulation of Kinase Signaling Pathways by AREs and GREs. AB - In response to environmental signals, kinases phosphorylate numerous proteins, including RNA-binding proteins such as the AU-rich element (ARE) binding proteins, and the GU-rich element (GRE) binding proteins. Posttranslational modifications of these proteins lead to a significant changes in the abundance of target mRNAs, and affect gene expression during cellular activation, proliferation, and stress responses. In this review, we summarize the effect of phosphorylation on the function of ARE-binding proteins ZFP36 and ELAVL1 and the GRE-binding protein CELF1. The networks of target mRNAs that these proteins bind and regulate include transcripts encoding kinases and kinase signaling pathways (KSP) components. Thus, kinase signaling pathways are involved in feedback regulation, whereby kinases regulate RNA-binding proteins that subsequently regulate mRNA stability of ARE- or GRE-containing transcripts that encode components of KSP. PMID- 26821048 TI - Evolutionary Steps in the Emergence of Life Deduced from the Bottom-Up Approach and GADV Hypothesis (Top-Down Approach). AB - It is no doubt quite difficult to solve the riddle of the origin of life. So, firstly, I would like to point out the kinds of obstacles there are in solving this riddle and how we should tackle these difficult problems, reviewing the studies that have been conducted so far. After that, I will propose that the consecutive evolutionary steps in a timeline can be rationally deduced by using a common event as a juncture, which is obtained by two counter-directional approaches: one is the bottom-up approach through which many researchers have studied the origin of life, and the other is the top-down approach, through which I established the [GADV]-protein world hypothesis or GADV hypothesis on the origin of life starting from a study on the formation of entirely new genes in extant microorganisms. Last, I will describe the probable evolutionary process from the formation of Earth to the emergence of life, which was deduced by using a common event-the establishment of the first genetic code encoding [GADV]-amino acids-as a juncture for the results obtained from the two approaches. PMID- 26821049 TI - Cross-Modal Re-Organization in Clinical Populations with Hearing Loss. AB - We review evidence for cross-modal cortical re-organization in clinical populations with hearing loss. Cross-modal plasticity refers to the ability for an intact sensory modality (e.g., vision or somatosensation) to recruit cortical brain regions from a deprived sensory modality (e.g., audition) to carry out sensory processing. We describe evidence for cross-modal changes in hearing loss across the age-spectrum and across different degrees of hearing impairment, including children with profound, bilateral deafness with cochlear implants, single-sided deafness before and after cochlear implantation, and adults with early-stage, mild-moderate, age-related hearing loss. Understanding cross-modal plasticity in the context of auditory deprivation, and the potential for reversal of these changes following intervention, may be vital in directing intervention and rehabilitation options for clinical populations with hearing loss. PMID- 26821050 TI - Ling's Adsorption Theory as a Mechanism of Membrane Potential Generation Observed in Both Living and Nonliving Systems. AB - The potential between two electrolytic solutions separated by a membrane impermeable to ions was measured and the generation mechanism of potential measured was investigated. From the physiological point of view, a nonzero membrane potential or action potential cannot be observed across the impermeable membrane. However, a nonzero membrane potential including action potential-like potential was clearly observed. Those observations gave rise to a doubt concerning the validity of currently accepted generation mechanism of membrane potential and action potential of cell. As an alternative theory, we found that the long-forgotten Ling's adsorption theory was the most plausible theory. Ling's adsorption theory suggests that the membrane potential and action potential of a living cell is due to the adsorption of mobile ions onto the adsorption site of cell, and this theory is applicable even to nonliving (or non-biological) system as well as living system. Through this paper, the authors emphasize that it is necessary to reconsider the validity of current membrane theory and also would like to urge the readers to pay keen attention to the Ling's adsorption theory which has for long years been forgotten in the history of physiology. PMID- 26821051 TI - Learning and Memory Recoveries in a Young Girl Treated with Growth Hormone and Neurorehabilitation. AB - Background-To describe the results obtained after treating a non growth hormone deficient 10-year-old girl who suffered asphyxia during delivery, resulting in important cognitive deficits, with growth hormone (GH) and neurorehabilitation. Methods-GH was administered (mg/day) at doses of 0.5 over three months followed by 0.9, every two weeks over three months, and then alternating 1.2 three days/week and 0.3 two days/week. Neurorehabilitation consisted of daily sessions of neurostimulation, speech therapy, occupational therapy and auditive stimulation. Treatment lasted nine months. Results-Scores obtained in all the areas treated showed that, at discharge, the patient clearly increased her cognitive abilities, memory and language competence index; her intelligence quotient score increased from 51 to 80, and the index of functional independence measure reached a value of 120 over 126 (maximal value). Conclusions-This case suggests that GH administration may play a role in improving cognitive deficits during neurorehabilitation in children with brain damage suffered during delivery. This agrees with the known effects of GH on cognition. PMID- 26821052 TI - Eicosopentaneoic Acid and Other Free Fatty Acid Receptor Agonists Inhibit Lysophosphatidic Acid- and Epidermal Growth Factor-Induced Proliferation of Human Breast Cancer Cells. AB - Many key actions of omega-3 (n-3) fatty acids have recently been shown to be mediated by two G protein-coupled receptors (GPCRs) in the free fatty acid receptor (FFAR) family, FFA1 (GPR40) and FFA4 (GPR120). n-3 Fatty acids inhibit proliferation of human breast cancer cells in culture and in animals. In the current study, the roles of FFA1 and FFA4 were investigated. In addition, the role of cross-talk between GPCRs activated by lysophosphatidic acid (LPA), and the tyrosine kinase receptor activated by epidermal growth factor (EGF), was examined. In MCF-7 and MDA-MB-231 human breast cancer cell lines, both LPA and EGF stimulated proliferation, Erk activation, Akt activation, and CCN1 induction. LPA antagonists blocked effects of LPA and EGF on proliferation in MCF-7 and MDA MB-231, and on cell migration in MCF-7. The n-3 fatty acid eicosopentaneoic acid inhibited LPA- and EGF-induced proliferation in both cell lines. Two synthetic FFAR agonists, GW9508 and TUG-891, likewise inhibited LPA- and EGF-induced proliferation. The data suggest a major role for FFA1, which was expressed by both cell lines. The results indicate that n-3 fatty acids inhibit breast cancer cell proliferation via FFARs, and suggest a mechanism involving negative cross talk between FFARS, LPA receptors, and EGF receptor. PMID- 26821054 TI - Epithelial-Mesenchymal Transition and Breast Cancer. AB - Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. There is increasing evidence supporting the role of epithelial-mesenchymal transition (EMT) in tumor cell progression, invasion, and metastasis. During the process of EMT, epithelial cancer cells acquire molecular alternations that facilitate the loss of epithelial features and gain of mesenchymal phenotype. Such transformation promotes cancer cell migration and invasion. Moreover, emerging evidence suggests that EMT is associated with the increased enrichment of cancer stem-like cells (CSCs) and these CSCs display mesenchymal characteristics that are resistant to chemotherapy and target therapy. However, the clinical relevance of EMT in human cancer is still under debate. This review will provide an overview of current evidence of EMT from studies using clinical human breast cancer tissues and its associated challenges. PMID- 26821055 TI - Variation in Gas and Volatile Compound Emissions from Human Urine as It Ages, Measured by an Electronic Nose. AB - The medical profession is becoming ever more interested in the use of gas-phase biomarkers for disease identification and monitoring. This is due in part to its rapid analysis time and low test cost, which makes it attractive for many different clinical arenas. One technology that is showing promise for analyzing these gas-phase biomarkers is the electronic nose--an instrument designed to replicate the biological olfactory system. Of the possible biological media available to "sniff", urine is becoming ever more important as it is easy to collect and to store for batch testing. However, this raises the question of sample storage shelf-life, even at -80 degrees C. Here we investigated the effect of storage time (years) on stability and reproducibility of total gas/vapour emissions from urine samples. Urine samples from 87 patients with Type 2 Diabetes Mellitus were collected over a four-year period and stored at -80 degrees C. These samples were then analyzed using FAIMS (field-asymmetric ion mobility spectrometry--a type of electronic nose). It was discovered that gas emissions (concentration and diversity) reduced over time. However, there was less variation in the initial nine months of storage with greater uniformity and stability of concentrations together with tighter clustering of the total number of chemicals released. This suggests that nine months could be considered a general guide to a sample shelf-life. PMID- 26821053 TI - Omega-3 Fatty Acids and Cancer Cell Cytotoxicity: Implications for Multi-Targeted Cancer Therapy. AB - Cancer is a major disease worldwide. Despite progress in cancer therapy, conventional cytotoxic therapies lead to unsatisfactory long-term survival, mainly related to development of drug resistance by tumor cells and toxicity towards normal cells. n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can exert anti-neoplastic activity by inducing apoptotic cell death in human cancer cells either alone or in combination with conventional therapies. Indeed, n-3 PUFAs potentially increase the sensitivity of tumor cells to conventional therapies, possibly improving their efficacy especially against cancers resistant to treatment. Moreover, in contrast to traditional therapies, n-3 PUFAs appear to cause selective cytotoxicity towards cancer cells with little or no toxicity on normal cells. This review focuses on studies investigating the cytotoxic activity of n-3 PUFAs against cancer cells via apoptosis, analyzing the molecular mechanisms underlying this effective and selective activity. Here, we highlight the multiple molecules potentially targeted by n-3 PUFAs to trigger cancer cell apoptosis. This analysis can allow a better comprehension of the potential cytotoxic therapeutic role of n 3 PUFAs against cancer, providing specific information and support to design future pre-clinical and clinical studies for a better use of n-3 PUFAs in cancer therapy, mainly combinational therapy. PMID- 26821057 TI - Intestinal ischemic preconditioning reduces liver ischemia reperfusion injury in rats. AB - The aim of the current study was to investigate whether intestinal ischemic preconditioning (IP) reduces damage to the liver during hepatic ischemia reperfusion (IR). Sprague Dawley rats were used to model liver IR injury, and were divided into the sham operation group (SO), IR group and IP group. The results indicated that IR significantly increased Bax, caspase 3 and NF-kappaBp65 expression levels, with reduced expression of Bcl-2 compared with the IP group. Compared with the IR group, the levels of AST, ALT, MPO, MDA, TNF-alpha and IL-1 were significantly reduced in the IP group. Immunohistochemistry for Bcl-2 and Bax indicated that Bcl-2 expression in the IP group was significantly increased compared with the IR group. In addition, IP reduced Bax expression compared with the IR group. The average liver injury was worsened in the IR group and improved in the IP group, as indicated by the morphological evaluation of liver tissues. The present study suggested that IP may alleviates apoptosis, reduce the release of pro-inflammatory cytokines, ameloriate reductions in liver function and reduce liver tissue injury. To conclude, IP provided protection against hepatic IR injury. PMID- 26821056 TI - Endocrine and Local IGF-I in the Bony Fish Immune System. AB - A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived), which has also been shown to be suppressed during infection in some studies. Nevertheless, data are still fragmentary. Some studies point to an important role of GH and IGF-I particularly during immune organ development and constitution. Even less is known about the potential relevance of local (autocrine/paracrine) IGF-I within adult and developing immune organs, and the distinct localization of IGF-I in immune cells and tissues of mammals and fish has not been systematically defined. Thus far, IGF-I has been localized in different mammalian immune cell types, particularly macrophages and granulocytes, and in supporting cells, but not in T-lymphocytes. In the present study, we detected IGF-I in phagocytic cells isolated from rainbow trout head kidney and, in contrast to some findings in mammals, in T-cells of a channel catfish cell line. Thus, although numerous analogies among mammals and teleosts exist not only for the GH/IGF-system, but also for the immune system, there are differences that should be further investigated. For instance, it is unclear whether the primarily reported role of GH/IGF-I in the innate immune response is due to the lack of studies focusing on the adaptive immune system, or whether it truly preferentially concerns innate immune parameters. Infectious challenges in combination with GH/IGF-I manipulations are another important topic that has not been sufficiently addressed to date, particularly with respect to developmental and environmental influences on fish growth and health. PMID- 26821058 TI - A Unidirectional Cell Switching Gate by Engineering Grating Length and Bending Angle. AB - On a microgrooved substrate, cells migrate along the pattern, and at random positions, reverse their directions. Here, we demonstrate that these reversals can be controlled by introducing discontinuities to the pattern. On "V-shaped grating patterns", mouse osteogenic progenitor MC3T3-E1 cells reversed predominately at the bends and the ends. The patterns were engineered in a way that the combined effects of angle- and length-dependence could be examined in addition to their individual effects. Results show that when the bend was placed closer to one end, migration behaviour of cells depends on their direction of approach. At an obtuse bend (135 degrees ), more cells reversed when approaching from the long segment than from the short segment. But at an acute bend (45 degrees ), this relationship was reversed. Based on this anisotropic behaviour, the designed patterns effectively allowed cells to move in one direction but blocked migrations in the opposing direction. This study demonstrates that by the strategic placement of bends and ends on grating patterns, we can engineer effective unidirectional switching gates that can control the movement of adherent cells. The knowledge developed in this study could be utilised in future cell sorting or filtering platforms without the need for chemotaxis or microfluidic control. PMID- 26821059 TI - Understanding the influence of surface properties of nanoparticles and penetration enhancers for improving bioavailability in eye tissues in vivo. AB - Nanoparticulate drug delivery systems, mucoadhesive polymers and penetration enhancers have been used individually to overcome ocular barriers and increase bioavailability to eye tissues. However the combined influence of mucoadhesive polymer coating and penetration enhancers on NP permeability has not been investigated. Hence, in this study, three types of core-shell nanoparticles with same hydrophobic core but different hydrophilic mucoadhesive shells were developed. Initially the influence of a single penetration enhancer (PE) [benzalkonium chloride (BAC)] on ocular permeability of all the three core-shell nanoparticles was studied. Then ocular permeability of a single nanoparticle system [polycaprolactone-pluronicF68 (PCL-PF68)] in presence of different types of PEs namely BAC, capric acid (CA), EDTA, sodium glycocolate (SG) and sodium taurocholate (ST) was studied. The results indicated that BAC differentially enhanced ocular permeability of nanoparticles depending on their surface properties. All the PEs except EDTA enhanced ocular permeability of PCL-PF68 nanoparticles to anterior part of the eye. BAC and CA showed increased bioavailability of PCL-PF68 nanoparticles in conjunctiva, SG in cornea, iris and ciliary body, and ST in cornea. Overall, the combination of PEs and surface properties of nanoparticles can differentially influence ocular permeability and bioavailability and can be advantageously used to develop improved ocular drug delivery systems. PMID- 26821061 TI - Benzophenone Ultrafast Triplet Population: Revisiting the Kinetic Model by Surface-Hopping Dynamics. AB - The photochemistry of benzophenone, a paradigmatic organic molecule for photosensitization, was investigated by means of surface-hopping ab initio molecular dynamics. Different mechanisms were found to be relevant within the first 600 fs after excitation; the long-debated direct (S1 -> T1) and indirect (S1 -> T2 -> T1) mechanisms for population of the low-lying triplet state are both possible, with the latter being prevalent. Moreover, we established the existence of a kinetic equilibrium between the two triplet states, never observed before. This fact implies that a significant fraction of the overall population resides in T2, eventually allowing one to revisit the usual spectroscopic assignment proposed by transient absorption spectroscopy. This finding is of particular interest for photocatalysis as well as for DNA damages studies because both T1 and T2 channels are, in principle, available for benzophenone-mediated photoinduced energy transfer toward DNA. PMID- 26821060 TI - pH-responsive PepFect cell-penetrating peptides. AB - A series of cell-penetrating PepFect peptide analogues was developed by substitutions of the galanin-derived N-terminal sequence. Histidine modifications were incorporated in order to make the peptides pH-responsive. The peptides were all able to form non-covalent complexes with an oligonucleotide cargo by co incubation in buffer. The complexes were characterized by dynamic light scattering and circular dichroism, and an assay to evaluate the peptide-cargo affinity was developed. Cellular bioactivity was studied in HeLa cells using a luciferase-based splice correction assay. In addition, the membrane interactions of the peptides in large unilammelar vesicles was studied using a calcein leakage assay. The effects of substitutions were found to be dependent of the non modified, C-terminal sequence of the peptides; for analogues of PepFect 3 we observed an increase in membrane activity and bioactivity for histidine containing analogues, whereas the same modifications introduced to PepFect 14 lead to a decreased bioactivity. Peptides modified with a leucine/histidine sequence were found to be pH responsive, complexes formed from these peptides were small at pH 7 and grew under acidic conditions. The most promising of the novel PepFect 3 analogues, PepFect 132 has a significantly higher bioactivity and membrane activity than the parent peptide PepFect 3. PMID- 26821062 TI - Luminescent Alkyne-Bearing Terbium(III) Complexes and Their Application to Bioorthogonal Protein Labeling. AB - Two new bifunctional macrocyclic chelate ligands that form luminescent terbium(III) complexes featuring an alkyne group for conjugation to (bio)molecules via the Cu(I)-catalyzed "click" reaction were synthesized. Upon ligation, the complexes exhibit a significant luminescent enhancement when excited at the lambda(max) of the "clicked" products. To demonstrate the utility of the complexes for luminescent labeling, they were conjugated in vitro to E. coli aspartate/glutamate-binding protein incorporating a genetically encoded p azido-L-phenylalanine or p-(azidomethyl)-L-phenylalanine residue. The complexes may prove useful for time-gated assay applications. PMID- 26821063 TI - Decreased sleep duration is associated with increased fMRI responses to emotional faces in children. AB - In adults and children, sleep loss is associated with affective dysregulation and increased responsivity to negative stimuli. Adult functional neuroimaging (fMRI) studies have demonstrated associations between restricted sleep and neural alterations in the amygdala and reward circuitry when viewing emotional picture and face stimuli. Despite this, few studies have examined the associations between short sleep duration and emotional responsivity in typically developing children, and no studies have investigated this relationship using fMRI. The current study examined the relationship between sleep duration and fMRI activation to emotional facial expressions in 15 male children (ages 7-11 years). During fMRI scanning, subjects viewed and made perceptual judgments regarding negative, neutral, and positive emotional faces. Maternal reported child sleep duration was negatively associated with (a) activation in the bilateral amygdala, left insula, and left temporal pole activation when viewing negative (i.e., fearful, disgust) vs. neutral faces, (b) right orbitofrontal and bilateral prefrontal activation when viewing disgust vs. neutral faces, and (c) bilateral orbitofrontal, right anterior cingulate, and left amygdala activation when viewing happy vs. neutral faces. Consistent with our prediction, we also noted that emotion-dependent functional connectivity between the bilateral amygdala and prefrontal cortex, cingulate, fusiform, and occipital cortex was positively associated with sleep duration. Paralleling similar studies in adults, these findings collectively suggest that decreased sleep duration in school-aged children may contribute to enhanced reactivity of brain regions involved in emotion and reward processing, as well as decreased emotion-dependent functional connectivity between the amygdala and brain regions associated with emotion regulation. PMID- 26821065 TI - Deciphering the true antiproliferative target of an MK2 activation inhibitor in glioblastoma. PMID- 26821064 TI - Dysregulated mitochondrial and chloroplast bioenergetics from a translational medical perspective (Review). AB - Mitochondria and chloroplasts represent endosymbiotic models of complex organelle development, driven by intense evolutionary pressure to provide exponentially enhanced ATP-dependent energy production functionally linked to cellular respiration and photosynthesis. Within the realm of translational medicine, it has become compellingly evident that mitochondrial dysfunction, resulting in compromised cellular bioenergetics, represents a key causative factor in the etiology and persistence of major diseases afflicting human populations. As a pathophysiological consequence of enhanced oxygen utilization that is functionally uncoupled from the oxidative phosphorylation of ADP, significant levels of reactive oxygen species (ROS) may be generated within mitochondria and chloroplasts, which may effectively compromise cellular energy production following prolonged stress/inflammatory conditions. Empirically determined homologies in biochemical pathways, and their respective encoding gene sequences between chloroplasts and mitochondria, suggest common origins via entrapped primordial bacterial ancestors. From evolutionary and developmental perspectives, the elucidation of multiple biochemical and molecular relationships responsible for errorless bioenergetics within mitochondrial and plastid complexes will most certainly enhance the depth of translational approaches to ameliorate or even prevent the destructive effects of multiple disease states. The selective choice of discussion points contained within the present review is designed to provide theoretical bases and translational insights into the pathophysiology of human diseases from a perspective of dysregulated mitochondrial bioenergetics with special reference to chloroplast biology. PMID- 26821066 TI - The clerodane diterpene casearin J induces apoptosis of T-ALL cells through SERCA inhibition, oxidative stress, and interference with Notch1 signaling. AB - T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy that preferentially affects children and adolescents. Over 50% of human T-ALLs possess activating mutations of Notch1. The clerodane diterpene casearin J (CJ) is a natural product that inhibits the sarcoendoplasmatic reticulum calcium ATPase (SERCA) pump and induces cell death in leukemia cells, but the molecular mechanism of cytotoxicity remains poorly understood. Here we show that owing to SERCA pump inhibition, CJ induces depletion of the endoplasmic reticulum calcium pools, oxidative stress, and apoptosis via the intrinsic signaling pathway. Moreover, Notch1 signaling is reduced in T-ALL cells with auto activating mutations in the HD-domain of Notch1, but not in cells that do not depend on Notch1 signaling. CJ also provoked a slight activation of NF-kappaB, and consistent with this notion a combined treatment of CJ and the NF-kappaB inhibitor parthenolide (Pt) led to a remarkable synergistic cell death in T-ALL cells. Altogether, our data support the concept that inhibition of the SERCA pump may be a novel strategy for the treatment of T-ALL with HD-domain-mutant Notch1 receptors and that additional treatment with the NF-kappaB inhibitor parthenolide may have further therapeutic benefits. PMID- 26821067 TI - TCL1 transgenic mouse model as a tool for the study of therapeutic targets and microenvironment in human B-cell chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia (CLL) is a B-cell malignancy with a mature phenotype. In spite of its relatively indolent nature, no radical cure is as yet available. CLL is not associated with either a unique cytogenetic or a molecular defect, which might have been a potential therapeutic target. Instead, several factors are involved in disease development, such as environmental signals which interact with genetic abnormalities to promote survival, proliferation and an immune surveillance escape. Among these, PI3-Kinase signal pathway alterations are nowadays considered to be clearly important. The TCL1 gene, an AKT co activator, is the cause of a mature T-cell leukemia, as well as being highly expressed in all B-CLL. A TCL1 transgenic mouse which reproduces leukemia with a distinct immunophenotype and similar to the course of the human B-CLL was developed several years ago and is widely used by many groups. This is a review of the CLL biology arising from work of many independent investigators who have used TCL1 transgenic mouse model focusing on pathogenetic, microenviroment and therapeutic targets. PMID- 26821068 TI - X-linked inhibitor of apoptosis protein mediates tumor cell resistance to antibody-dependent cellular cytotoxicity. AB - Inflammatory breast cancer (IBC) is the deadliest, distinct subtype of breast cancer. High expression of epidermal growth factor receptors [EGFR or human epidermal growth factor receptor 2 (HER2)] in IBC tumors has prompted trials of anti-EGFR/HER2 monoclonal antibodies to inhibit oncogenic signaling; however, de novo and acquired therapeutic resistance is common. Another critical function of these antibodies is to mediate antibody-dependent cellular cytotoxicity (ADCC), which enables immune effector cells to engage tumors and deliver granzymes, activating executioner caspases. We hypothesized that high expression of anti apoptotic molecules in tumors would render them resistant to ADCC. Herein, we demonstrate that the most potent caspase inhibitor, X-linked inhibitor of apoptosis protein (XIAP), overexpressed in IBC, drives resistance to ADCC mediated by cetuximab (anti-EGFR) and trastuzumab (anti-HER2). Overexpression of XIAP in parental IBC cell lines enhances resistance to ADCC; conversely, targeted downregulation of XIAP in ADCC-resistant IBC cells renders them sensitive. As hypothesized, this ADCC resistance is in part a result of the ability of XIAP to inhibit caspase activity; however, we also unexpectedly found that resistance was dependent on XIAP-mediated, caspase-independent suppression of reactive oxygen species (ROS) accumulation, which otherwise occurs during ADCC. Transcriptome analysis supported these observations by revealing modulation of genes involved in immunosuppression and oxidative stress response in XIAP-overexpressing, ADCC resistant cells. We conclude that XIAP is a critical modulator of ADCC responsiveness, operating through both caspase-dependent and -independent mechanisms. These results suggest that strategies targeting the effects of XIAP on caspase activation and ROS suppression have the potential to enhance the activity of monoclonal antibody-based immunotherapy. PMID- 26821069 TI - Downregulation of CDC27 inhibits the proliferation of colorectal cancer cells via the accumulation of p21Cip1/Waf1. AB - Dysregulated cell cycle progression has a critical role in tumorigenesis. Cell division cycle 27 (CDC27) is a core subunit of the anaphase-promoting complex/cyclosome, although the specific role of CDC27 in cancer remains unknown. In our study, we explored the biological and clinical significance of CDC27 in colorectal cancer (CRC) growth and progression and investigated the underlying molecular mechanisms. Results showed that CDC27 expression is significantly correlated with tumor progression and poor patient survival. Functional assays demonstrated that overexpression of CDC27 promoted proliferation in DLD1 cells, whereas knockdown of CDC27 in HCT116 cells inhibited proliferation both in vitro and in vivo. Further mechanistic investigation showed that CDC27 downregulation resulted in G1/S phase transition arrest via the significant accumulation of p21 in HCT116 cells, and the upregulation of CDC27 promoted G1/S phase transition via the attenuation of p21 in DLD1 cells. Furthermore, we also demonstrated that CDC27 regulated inhibitor of DNA binding 1 (ID1) protein expression in DLD1 and HCT116 cells, and rescue assays revealed that CDC27 regulated p21 expression through modulating ID1 expression. Taken together, our results indicate that CDC27 contributes to CRC cell proliferation via the modulation of ID1-mediated p21 regulation, which offers a novel approach to the inhibition of tumor growth. Indeed, these findings provide new perspectives for the future study of CDC27 as a target for CRC treatment. PMID- 26821071 TI - Anthocyanidins but not anthocyanins inhibit P-glycoprotein-mediated calcein extrusion - possible implication for orally administered drugs. AB - P-glycoprotein (P-gp) inhibition represents a promising therapeutic strategy for oncologic patients. The inhibition by naturally occurring anthocyans would bring certain benefits. Unfortunately, due to the low bioavailability and consequently low blood level, they cannot be used for cancer therapy. However, due to the food supplementation, significant concentration can raise up in the intestine, where P gp is abundantly expressed. As many drugs are orally taken, simultaneous administration might affect the concentration of these drugs in the blood. Here, we found that anthocyanidins (aglycons) but not anthocyanins (glycosides) can significantly inhibit P-gp up to 60% of positive control, verapamil. This inhibitory activity was observed for 500 MUm concentrations of malvidin and pelargonidin. We conclude that these compounds may be the source of food-drug interactions either for orally taken drugs or for intravenously administered drugs eliminated via biliary excretion which are the substrates of P-gp. PMID- 26821072 TI - Justifications of feticide. AB - This qualitative research explores the justifications that Israeli women provided for their decision to end their late-stage pregnancies, or in other words to undergo feticide. A constructivist approach was used, as it recognizes the significance of sociocultural narratives in the construction of people's experiences. Data from in-depth interviews were analyzed using an adapted version of constant comparative analysis to identify and develop categories and thematic patterns. Three main themes were identified, which incorporated the various justifications women use in explaining their decision to undergo feticide: justifications related to the mother and her family; justifications related to the fetus; and justifications related to the views of medical professionals and society at large. The analysis process further revealed an overall conceptualization: wrongful life and a wrongful birth, which underlie the 3 themes. In the justification process, the women drew on a number of strategies to uphold their positions as moral caring human beings and good mothers, including denial of injury, appeal to higher loyalties, and defense of necessity. These justifications seem to have failed, as the women continued to struggle with the morality of their decision. Women's difficulties were grounded in contradicting social messages concerning feticide, as feticide is a relatively common yet socially unrecognized and undiscussed procedure in Israel. The findings highlight the interface between personal experience and social phenomena and call for an open social discourse on feticide. (PsycINFO Database Record PMID- 26821070 TI - miR-302 regulates pluripotency, teratoma formation and differentiation in stem cells via an AKT1/OCT4-dependent manner. AB - Pluripotency makes human pluripotent stem cells (hPSCs) promising for regenerative medicine, but the teratoma formation has been considered to be a major obstacle for their clinical applications. Here, we determined that the downregulation of miR-302 suppresses the teratoma formation, hampers the self renewal and pluripotency, and promotes hPSC differentiation. The underlying mechanism is that the high endogenous expression of miR-302 suppresses the AKT1 expression by directly targeting its 3'UTR and subsequently maintains the pluripotent factor OCT4 at high level. Our findings reveal that miR-302 regulates OCT4 by suppressing AKT1, which provides hPSCs two characteristics related to their potential for clinical applications: the benefit of pluripotency and the hindrance of teratoma formation. More importantly, we demonstrate that miR-302 upregulation cannot lead OCT4 negative human adult mesenchymal stem cells (hMSCs) to acquire the teratoma formation in vivo. Whether miR-302 upregulation can drive hMSCs to acquire a higher differentiation potential is worthy of deep investigation. PMID- 26821074 TI - Effect of Bifidobacterium breve M-16V supplementation on faecal bifidobacteria in growth restricted very preterm infants - analysis from a randomised trial. AB - BACKGROUND: Gut development, function and colonisation are impaired in animal models of prematurity with intrauterine growth restriction (IUGR). The effect of Bifidobacterium breve (B. breve) supplementation on faecal bifidobacteria in small for gestational age (SGA: birth weight <10th centile due to IUGR) preterm infants is not known. OBJECTIVE: We compared B. breve M-16V supplementation effect on faecal bifidobacteria in preterm (<33 weeks) SGA versus non-SGA infants in the two arms of our randomised controlled trial. RESULTS: There were no baseline differences in the proportion of detectable B. breve counts between SGA versus non-SGA infants [probiotic: 7 (33%) versus 22 (42%), p = 0.603; placebo: 1 (6%) versus 1 (2%), p = 0.429]. B. breve counts did not differ between SGA and non-SGA infants in response to treatment (p = 0.589), after adjusting for baseline count (p < 0.001) and treatment allocation (p < 0.001). An interaction term between growth status and treatment showed negligible change (p = 0.938). Probiotic treated SGA infants reached full feeds earlier than SGA controls (HR 2.00, 95% CI 1.05-3.82, p = 0.035): Median (IQR): 16 (12-26) versus 19 (11-25) days, after adjustment for age at starting feeds and gestation <28 weeks. CONCLUSION: Response to B. breve M-16V supplementation was not significantly different in preterm (<33 weeks) SGA versus non-SGA infants. PMID- 26821073 TI - Neuropharmacological characterization of the oneirogenic Mexican plant Calea zacatechichi aqueous extract in mice. AB - This study evaluates the neuropharmacological effects of the aqueous extract of the Mexican plant Calea zacatechichi Schltdl., which is commonly used in folk medicine to treat cough, asthma, and gastrointestinal disorders. Moreover, it has been used for centuries in traditional rituals based on divination and is thought to possess hallucinogenic activity. To test the neuropharmacological effects of the aqueous extract of C. zacatechichi we used mouse models of convulsions, an elevated plus-maze test and measured locomotor activity. We also evaluated the effect of the extract on antidepressant-like behavior in forced swim test, as well as on muscular strength in a grip test. Moreover the antinociceptive action of the extract was evaluated in the hot-plate and writhing tests. The chemical composition of the extract was evaluated using LC-MS techniques. The aqueous extract of C. zacatechichi did not affect any of the parameters measured in seizure models. It had also no influence on anxiety, exploratory behavior and muscular strength in the applied doses. On the other hand, the extract exhibited antinociceptive effect in the mouse model of abdominal pain. Chemical characterization of the extract showed the presence of chlorogenic acid, acacetin, and germacranolides. Based on this report we suggest that aqueous extract of C. zacatechichi has insignificant neuropharmacological effects in vivo and reduces abdominal pain perception. Our results, together with previous studies showing beneficial effects of the extracts obtained from C. zacatechichi suggest that these preparations may be used to treat medical conditions. PMID- 26821076 TI - A Framework of Statistical Tests For Comparing Mean and Covariance Structure Models. AB - Although statistical procedures are well-known for comparing hierarchically related (nested) mean and covariance structure models, statistical tests for comparing non-hierarchically related (nonnested) models have proven more elusive. Although isolated attempts at statistical tests of non-hierarchically related models have been made, none exist within the commonly used maximum likelihood estimation framework, thereby compromising these methods' accessibility and general applicability. Building on general theory developed by Vuong (1989) and techniques for establishing the relation between covariance structure models ( Raykov & Penev, 1999 ), this work provides a general paradigm for conducting statistical tests on competing mean and covariance structure models. The proposed framework is appropriate for hierarchically related models as well as non hierarchically related models. In developing the structure of the framework, key aspects of model equivalence, relation, and comparison are unified. An illustration demonstrates its use. PMID- 26821075 TI - Confirmatory Factor Analysis and Profile Analysis via Multidimensional Scaling. AB - This paper describes the Confirmatory Factor Analysis (CFA) parameterization of the Profile Analysis via Multidimensional Scaling (PAMS) model to demonstrate validation of profile pattern hypotheses derived from multidimensional scaling (MDS). Profile Analysis via Multidimensional Scaling (PAMS) is an exploratory method for identifying major profiles in a multi-subtest test battery. Major profile patterns are represented as dimensions extracted from a MDS analysis. PAMS represents an individual observed score as a linear combination of dimensions where the dimensions are the most typical profile patterns present in a population. While the PAMS approach was initially developed for exploratory purposes, its results can later be confirmed in a different sample by CFA. Since CFA is often used to verify results from an exploratory factor analysis, the present paper makes the connection between a factor model and the PAMS model, and then illustrates CFA with a simulated example (that was generated by the PAMS model) and at the same time with a real example. The real example demonstrates confirmation of PAMS exploratory results by using a different sample. Fit indexes can be used to indicate whether the CFA reparameterization as a confirmatory approach works for the PAMS exploratory results. PMID- 26821077 TI - Structural Equation Modeling of Multivariate Time Series. AB - The covariance structure of a vector autoregressive process with moving average residuals (VARMA) is derived. It differs from other available expressions for the covariance function of a stationary VARMA process and is compatible with current structural equation methodology. Structural equation modeling programs, such as LISREL, may therefore be employed to fit the model. Particular attention is given to assumptions concerning the process before the first observation. An application to a repeated time series is used to demonstrate the effect of these assumptions on the structure of the reproduced covariance matrix. PMID- 26821078 TI - Multidimensional Unfolding by Nonmetric Multidimensional Scaling of Spearman Distances in the Extended Permutation Polytope. AB - A multidimensional unfolding technique that is not prone to degenerate solutions and is based on multidimensional scaling of a complete data matrix is proposed: distance information about the unfolding data and about the distances both among judges and among objects is included in the complete matrix. The latter information is derived from the permutation polytope supplemented with the objects, called the preference sphere. In this sphere, distances are measured that are closely related to Spearman's rank correlation and that are comparable among each other so that an unconditional approach is reasonable. In two simulation studies, it is shown that the proposed technique leads to acceptable recovery of given preference structures. A major practical advantage of this unfolding technique is its relatively easy implementation in existing software for multidimensional scaling. PMID- 26821079 TI - Examining Factor Score Distributions to Determine the Nature of Latent Spaces. AB - Similarities between latent class models with K classes and linear factor models with K - 1 factors are investigated. Specifically, the mathematical equivalence between the covariance structure of the two models is discussed, and a Monte Carlo simulation is performed using generated data that represents both latent factors and latent classes with known amounts of overlap. It is shown that, under certain conditions, the distribution of factor scores can be related to the continuity of the latent space via tests of multimodality as suggested by McDonald (1967) . PMID- 26821080 TI - A Confirmatory Analysis of Item Reliability Trends (CAIRT): Differentiating True Score and Error Variance in the Analysis of Item Context Effects. AB - Numerous studies have shown increasing item reliabilities as an effect of the item position in personality scales. Traditionally, these context effects are analyzed based on item-total correlations. This approach neglects that trends in item reliabilities can be caused either by an increase in true score variance or by a decrease in error variance. This article presents the Confirmatory Analysis of Item Reliability Trends (CAIRT) that allows estimating both trends separately within a structural equation modeling framework. Results of a simulation study prove the CAIRT method to provide reliable and independent parameter estimates; the power exceeds the analysis of item-total correlations. We present an empirical application to self- and peer ratings collected in an Internet-based experiment. Results show that reliability trends are caused by increasing true score variance in self-ratings and by decreasing error variance in peer ratings. PMID- 26821081 TI - Addressing Moderated Mediation Hypotheses: Theory, Methods, and Prescriptions. AB - This article provides researchers with a guide to properly construe and conduct analyses of conditional indirect effects, commonly known as moderated mediation effects. We disentangle conflicting definitions of moderated mediation and describe approaches for estimating and testing a variety of hypotheses involving conditional indirect effects. We introduce standard errors for hypothesis testing and construction of confidence intervals in large samples but advocate that researchers use bootstrapping whenever possible. We also describe methods for probing significant conditional indirect effects by employing direct extensions of the simple slopes method and Johnson-Neyman technique for probing significant interactions. Finally, we provide an SPSS macro to facilitate the implementation of the recommended asymptotic and bootstrapping methods. We illustrate the application of these methods with an example drawn from the Michigan Study of Adolescent Life Transitions, showing that the indirect effect of intrinsic student interest on mathematics performance through teacher perceptions of talent is moderated by student math self-concept. PMID- 26821082 TI - 2006 Tanaka Award Winner. PMID- 26821083 TI - Recognition of MBR Reviewers. PMID- 26821084 TI - Clinical and biological significance of transcription termination factor, RNA polymerase I in human liver hepatocellular carcinoma. AB - Recent studies have indicated that increased ribosomal activity contributes to cancer progression. Transcription termination factor, RNA polymerase I (TTF1) acts as a transcription factor for RNA polymerase I. However, the role which TTF1 plays in cancer progression still remains unknown. The present study aimed to determine whether TTF1 plays a critical role in the progression of human liver hepatocellular carcinoma (HCC). In the present study, quantitative real-time reverse transcription polymerase chain reaction was conducted to evaluate TTF1 mRNA expression in 60 HCC tissue samples in order to determine the clinicopathological significance of TTF1. To investigate whether the expression levels of TTF1 were associated known gene signatures which represented ribosomal activity, we applied gene set enrichment analysis (GSEA) to HCC cases in The Cancer Genome Atlas (TCGA) a. We also performed in vitro proliferation assays using TTF1-overexpressing HCC cells. TTF1 expression was significantly higher in HCC tumor tissues than in adjacent liver tissues (P<0.001). The overall survival (OS) of patients with high TTF1 expression levels was significantly shorter than that of patients with low TTF1 expression (P=0.027). Multivariate analysis indicated that TTF1 expression was an independent prognostic factor for OS (P=0.020). GSEA revealed significant associations between TTF1 expression and gene sets involved in ribosomal function. In vitro, cell proliferation and rRNA transcription were significantly promoted by overexpression of TTF1 in the HCC cell lines HuH-7 and HepG2. From these results, it was suggested that TTF1 participate in poor prognoses and play a role in tumor cell growth in HCC, possibly by upregulating ribosomal activity. In conclusion, we first propose that TTF1 may be a novel biomarker and therapeutic target in HCC. Increased expression of TTF1 was significantly associated with poor prognosis in two independent sets of HCC cases. Furthermore, in vitro experiments provided an explanation for clinical data showing that overexpression of TTF1 contributed to the proliferation of cancer cells. PMID- 26821086 TI - Helium Tagging Infrared Photodissociation Spectroscopy of Reactive Ions. AB - The interrogation of reaction intermediates is key for understanding chemical reactions; however their direct observation and study remains a considerable challenge. Mass spectrometry is one of the most sensitive analytical techniques, and its use to study reaction mixtures is now an established practice. However, the information that can be obtained is limited to elemental analysis and possibly to fragmentation behavior, which is often challenging to analyze. In order to extend the available experimental information, different types of spectroscopy in the infrared and visible region have been combined with mass spectrometry. Spectroscopy of mass selected ions usually utilizes the powerful sensitivity of mass spectrometers, and the absorption of photons is not detected as such but rather translated to mass changes. One approach to accomplish such spectroscopy involves loosely binding a tag to an ion that will be removed by absorption of one photon. We have constructed an ion trapping instrument capable of reaching temperatures that are sufficiently low to enable tagging by helium atoms in situ, thus permitting infrared photodissociation spectroscopy (IRPD) to be carried out. While tagging by larger rare gas atoms, such as neon or argon is also possible, these may cause significant structural changes to small and reactive species, making the use of helium highly beneficial. We discuss the "innocence" of helium as a tag in ion spectroscopy using several case studies. It is shown that helium tagging is effectively innocent when used with benzene dications, not interfering with their structure or IRPD spectrum. We have also provided a case study where we can see that despite its minimal size there are systems where He has a huge effect. A strong influence of the He tagging was shown in the IRPD spectra of HCCl(2+) where large spectral shifts were observed. While the presented systems are rather small, they involve the formation of mixtures of isomers. We have therefore implemented two-color experiments where one laser is employed to selectively deplete a mixture by one (or more) isomer allowing helium tagging IRPD spectra of the remaining isomer(s) to be recorded via the second laser. Our experimental setup, based on a linear wire quadrupole ion trap, allows us to deplete almost 100% of all helium tagged ions in the trap. Using this special feature, we have developed attenuation experiments for determination of absolute photofragmentation cross sections. At the same time, this approach can be used to estimate the representation of isomers in a mixture. The ultimate aim is the routine use of this instrument and technique to study a wide range of reaction intermediates in catalysis. To this end, we present a study of hypervalent iron(IV)-oxo complexes ([(L)Fe(O)(NO3)](+)). We show that we can spectroscopically differentiate iron complexes with S = 1 and S = 2 according to the stretching vibrations of a nitrate counterion. PMID- 26821085 TI - Superoxide dismutase activity and gene expression levels in Saudi women with recurrent miscarriage. AB - The antioxidant activities of superoxide dismutase 1 (SOD1) and SOD2, as well as the levels of the oxidant superoxide anion (SOA) and the micronutrients zinc (Zn), copper (Cu) and manganese (Mn), were assayed in plasma, whole blood and placental tissue of non-pregnant (NP), healthy pregnant (HP) women and recurrent miscarriage (RM) patients. The results showed that SOD1 and SOD2 activities and the levels of Zn, Cu and Mn in plasma and whole blood of HP women were slightly, but significantly lower, and even more significantly decreased in RM patients compared to those observed in NP women (P<0.05 and P<0.0001, respectively). Additionally, whereas plasma SOD1 and SOD2 activities and Zn, Cu and Mn levels were significantly lower in RM patients, those of whole blood and placental tissue were significantly lower when compared to HP women (P<0.001 and P<0.0001, respectively). Concurrently, there were consistent increases of equal magnitude and statistical significance in SOA levels in all the assayed samples as identified by a comparison between the subjects. The findings thus supported oxidative metabolism and excessive reactive oxygen species generation. The resultant oxidative stress, identified in whole blood and placental tissues of RM patients, may have been a primary cause of RM. Dietary supplementation of Zn, Cu and Mn may be beneficial to these patients pre- and post-conception. PMID- 26821088 TI - Cyclometalated gold(III) trioxadiborrin complexes: studies of the bonding and excited states. AB - Trioxadiborrins are chelating ligands that assemble in dehydration reactions of boronic acids. They are structurally related to beta-diketonate ligands, but have a 2-charge. Little is known of the bonding properties of trioxadiborrin ligands. Presented here are density-functional theory (DFT) studies of cyclometalated gold(III) trioxadiborrins. Substituent effects are evaluated, and comparison is made to the cyclometalating 2-(4-tolyl)pyridine (tpy) ligand on gold. The tpy ligand binds more strongly than any trioxadiborrin ligand considered here, and the two ligands bind competitively to gold. The 1,3-diphenyl trioxadiborrin ligand of 1 has a larger absolute binding enthalpy to gold than its beta diketonate analogue. Conjugation between boron and aryl substituents delocalizes charge and attenuates the trioxadiborrin's binding capacity. Steric effects that disrupt conjugation between boron and aryl substituents cause the trioxadiborrin to chelate more tightly. Fragment bond orders are divided into in-plane and out of-plane contributions for square planar 1. In-plane bonding accounts for 88% of bond order between (tpy)Au2+ and the trioxadiborrin ligand. Cyclometalated gold(III) trioxadiborrin complexes were previously shown to be phosphorescent. Spin-unrestricted triplet-state geometry optimizations find that the ten largest excited-state distortions all occur on the tpy ligand. A plot of spin density in triplet 1 shows spin to reside predominantly on tpy. The 77 K luminescence spectrum of 1 is reported here. Time-dependent DFT and configuration interaction singles calculations (corrected for doubles excitations) overestimate the emission energy by ~ 0.12 eV. PMID- 26821087 TI - Cross-subtype detection of HIV-1 using reverse transcription and recombinase polymerase amplification. AB - A low complexity diagnostic test that rapidly and reliably detects HIV infection in infants at the point of care could facilitate early treatment, improving outcomes. However, many infant HIV diagnostics can only be performed in laboratory settings. Recombinase polymerase amplification (RPA) is an isothermal amplification technology that can rapidly amplify proviral DNA from multiple subtypes of HIV-1 in under twenty minutes without complex equipment. In this study we added reverse transcription (RT) to RPA to allow detection of both HIV-1 RNA and DNA. We show that this RT-RPA HIV-1 assay has a limit of detection of 10 30 copies of an exact sequence matched DNA or RNA, respectively. In addition, at 100 copies of RNA or DNA, the assay detected 171 of 175 (97.7%) sequence variants that represent all the major subtypes and recombinant forms of HIV-1 Groups M and O. This data suggests that the application of RT-RPA for the combined detection of HIV-1 viral RNA and proviral DNA may prove a highly sensitive tool for rapid and accurate diagnosis of infant HIV. PMID- 26821089 TI - Correction: Can Population-Level Laterality Stem from Social Pressures? Evidence from Cheek Kissing in Humans. AB - [This corrects the article DOI: 10.1371/journal.pone.0124477.]. PMID- 26821090 TI - Rh(III)-Catalyzed Redox-Neutral Annulation of Primary Benzamides with Diazo Compounds: Approach to Isoquinolinones. AB - Reported herein is a Rh-catalyzed redox-neutral annulation of primary benzamides with diazo compounds, representing an efficient and economic protocol to isoquinolinones. The procedure exhibited good functional group tolerability, scalability, and regioselectivity, obviating the need for oxidants, and only environmentally benign N2 and H2O were released. Further utilization of the method provided an alternative route to functionalized isoquinolines. PMID- 26821091 TI - Not just loading and age: the dynamics of osteoarthritis, obesity and inflammation. PMID- 26821092 TI - Asbestos exposure: challenges for Australian clinicians. PMID- 26821093 TI - Malaria detection using breath biomarkers. PMID- 26821095 TI - Using a multidisciplinary approach to combat the burden of asbestos-related disease. PMID- 26821096 TI - Developing competence in biostatistics and research methodology during medical specialty training. PMID- 26821097 TI - A broad perspective on anatomy education: celebrating teaching diversity and innovations. PMID- 26821098 TI - A multidisciplinary renal genetics clinic improves patient diagnosis. PMID- 26821099 TI - How severe was the 2015 influenza season in Australia? PMID- 26821100 TI - Severe ulcerative herpes zoster. PMID- 26821101 TI - Management of pregnancy in women with rheumatoid arthritis. AB - Rheumatoid arthritis (RA) disease activity may improve during pregnancy but postpartum flares are common. Patients taking disease-modifying antirheumatic drugs should be counselled about effective contraception. Knowledge about drug safety in pregnancy is limited but the Therapeutic Goods Administration categories and online resources are a guide to the data currently available. Begin prepregnancy counselling as early as possible to allow for cessation of teratogenic medications and optimisation of RA disease control. For unplanned pregnancies, cease teratogenic medications immediately and refer to a genetic counsellor and maternal-fetal medicine specialist for risk assessment and advice. PMID- 26821102 TI - Ten years of publicly funded biological disease-modifying antirheumatic drugs in Australia. AB - Biological disease-modifying antirheumatic drugs (bDMARDs) for rheumatoid arthritis (RA) treatment were among the first high-cost medicines to be subsidised in Australia. High-cost medicines pose several challenges to the Australian National Medicines Policy, which aims to provide timely access to effective medicines at a cost individuals and the community can afford. Thus, novel restriction criteria were developed to encourage cost-effective use of bDMARDs. Government expenditure on bDMARD subsidies for RA treatment grew to about $383 million in 2014. Evidence that initiation and continuation criteria for bDMARDs meet usually applied cost-benefit criteria is lacking. The combined expenditure on tocilizumab, certolizumab pegol and golimumab (added to the Australian Government's Pharmaceutical Benefits Scheme in 2010) was $93 million in 2014, which is 210% over the initial estimate. Present and future challenges with regard to bDMARDs for RA and other high-cost drugs include improved expenditure predictions, monitoring of cost-effectiveness in relation to actual use and strategic development, regulation and use of biosimilars. Ten years of documentation on clinical and laboratory findings indicating eligibility to initiate and continue on bDMARDs remains un-used. These data represent an untapped opportunity to promote quality of use of bDMARDs and biosimilars and to improve cost predictions for high-cost drugs. PMID- 26821103 TI - Inappropriate care in medicine. PMID- 26821104 TI - Vertebroplasty is not a do-not-do treatment. PMID- 26821105 TI - Acting on potentially inappropriate care. PMID- 26821106 TI - SEPSIS KILLS: early intervention saves lives. AB - OBJECTIVE: To implement a statewide program for the early recognition and treatment of sepsis in New South Wales, Australia. SETTING: Ninety-seven emergency departments in NSW hospitals. INTERVENTION: A quality improvement program (SEPSIS KILLS) that promoted intervention within 60 minutes of recognition, including taking of blood cultures, measuring serum lactate levels, administration of intravenous antibiotics, and fluid resuscitation. MAIN OUTCOME MEASURES: Time to antibiotics and fluid resuscitation; mortality rates and length of stay. RESULTS: Data for 13 567 patients were entered into the database. The proportion of patients receiving intravenous antibiotics within 60 minutes of triage increased from 29.3% in 2009-2011 to 52.2% in 2013. The percentage for whom a second litre of fluid was started within 60 minutes rose from 10.6% to 27.5% (each P < 0.001). The proportion of patients classed as Australasian Triage Scale (ATS) 1 increased from 2.3% in 2009-2011 to 4.2% in 2013, and the proportion classed as ATS 2 rose from 40.7% in 2009-2011 to 60.7% in 2013 (P < 0.001). There was a linear decrease in mortality from 19.3% in 2009-2011 to 14.1% in 2013; there was also a significant decline in time in intensive care and total length of stay (each P < 0.0001). The mortality rate for patients with severe sepsis (serum lactate >= 4 mmol/L or systolic blood pressure [SBP] < 90 mmHg) was 19.7%. The mortality rates for patients with severe sepsis admitted to intensive care and for those admitted to a ward did not change significantly over time. The proportion of patients with uncomplicated sepsis (SBP >= 90 mmHg, serum lactate < 4 mmol/L) transferred to a ward increased, and the mortality rate after transfer increased from 3.2% in 2009-2011 to 6.2% in 2013 (P < 0.05). The survival benefit was greatest for patients with evidence of haemodynamic instability (SBP < 90 mmHg) but normal lactate levels (P = 0.03). CONCLUSIONS: The SEPSIS KILLS program has improved the process of care for patients with sepsis in NSW hospitals. The program has focused attention on sepsis management in the wards. PMID- 26821107 TI - A survey of Sydney general practitioners' management of patients with chronic hepatitis B. AB - OBJECTIVE: To examine the chronic hepatitis B (CHB) assessment and management practices of general practitioners in the Sydney and South Western Sydney Local Health Districts, areas with a high prevalence of CHB, and to obtain their views on alternative models of care. DESIGN, SETTING AND PARTICIPANTS: We used a descriptive, cross-sectional study design to survey GPs who had seen at least one patient aged 18 years or over who had been notified as having CHB to the Public Health Unit between 1 June 2012 and 31 May 2013. There were 213 eligible GPs; the response rate was 57.7%. MAIN OUTCOME MEASURES: The CHB assessment, management and referral practices of the GPs, and their opinions about different models of care. RESULTS: Most GPs (78.9%) were at least reasonably confident about managing CHB. GPs were generally most comfortable with a model of care that involved initial referral to a specialist; managing CHB without specialist input or with only review by a specialised nurse practitioner were less popular. CONCLUSION: These results suggest that barriers, including dependence on specialist input, still hinder the appropriate assessment and management of CHB patients by GPs. Well designed and targeted support programs that include specialist support are needed if there is to be a successful shift to an increased role for GPs in the model of care for managing CHB. PMID- 26821108 TI - Timeliness of lung cancer care in Victoria: a retrospective cohort study. AB - OBJECTIVE: To assess factors associated with second-line delays in the management of patients diagnosed with lung cancer. DESIGN, SETTING AND PARTICIPANTS: A retrospective cohort study, conducted in six public and two private Victorian hospitals, of 1417 patients aged 18 years or more who were diagnosed between July 2011 and October 2014 with an incident case of lung cancer identified by International Classification of Diseases, 10th revision codes (C34.0-C34.9, Z85.1, Z85.2) on the basis of either a clinical or pathological diagnosis. OUTCOME MEASURES: Time intervals between referral, diagnosis and initial definitive management. RESULTS: The median time from referral to diagnosis was 15 days (interquartile range [IQR], 5-36); from diagnosis to initial definitive management, 30 days (IQR, 6-84); and from referral to initial definitive management, 53 days (IQR, 25-106). Factors that were significantly associated with delay between referral and initial definitive management include declining or not being referred to palliative care (hazard ratio [HR], v patients referred for palliation, 0.73; 95% CI, 0.62-0.86; P < 0.001), and being treated in a public hospital (HR, v patients managed in a private hospital, 0.55; 95% CI, 0.48 0.64; P < 0.001). The median time from referral to initial definitive management in public and private hospitals was 61 days (IQR, 35-118) and 30 days (IQR, 13 76) respectively; 48% of patients in public hospitals waited longer than the British National Health Service target of a maximum 62 days between referral and first definitive treatment. CONCLUSION: There are significant delays at various stages of the patient journey after referral for initial definitive management. Having a greater understanding of these delays will enable strategies to be developed that improve the timeliness of care for patients with lung cancer. PMID- 26821109 TI - Influenza vaccine effectiveness in general practice and in hospital patients in Victoria, 2011-2013. AB - OBJECTIVE: To compare influenza vaccine effectiveness in the general practice and hospital settings. DESIGN: Analysis of annual case test-negative studies. SETTING: Victorian sentinel hospitals and general practices, 2011-2013. PARTICIPANTS: Patients presenting to general practitioners, or those admitted to hospital with an influenza-like illness who were tested for influenza using a polymerase chain reaction assay. Cases were patients with a positive test result for influenza; non-cases (controls) had a negative test result. MAIN OUTCOME MEASURES: Vaccine effectiveness against laboratory-confirmed influenza. RESULTS: Hospitalised patients were on average older and reported a higher proportion of comorbidities than general practice patients. The pooled estimate of influenza vaccine effectiveness against laboratory-confirmed infection for the 3 years was 50% (95% CI, 26%-66%) for general practice patients and 39% (95% CI, 28%-47%) for patients admitted to hospital. CONCLUSIONS: Influenza vaccines appeared to be similarly modestly effective in the general practice and hospital settings. Influenza vaccination appears to prevent hospital admission by preventing symptomatic infection rather than by attenuating the severity of illness. PMID- 26821110 TI - Repeat exposure to active tuberculosis and risk of re-infection. PMID- 26821111 TI - A case of bilateral endogenous bacterial endophthalmitis from Streptococcus pneumoniae bacteraemia. PMID- 26821112 TI - Conclaves and concurrent expert evidence: a positive development in Australian legal practice? AB - Many Australian courts now prefer pre-hearing meetings of experts (conclaves) being convened to prepare joint reports to identify areas of agreement and disagreement, followed by concurrent expert evidence at trial. This contrasts to the traditional approach where experts did not meet before trial and did not give evidence together. Most judges, lawyers and expert witnesses favour this as a positive development in Australian legal practice, at least for civil disputes. This new approach affects medical practitioners who are called on to give expert evidence, or who are parties to disputes before the courts. Arguably, it is too soon to tell whether the relative lack of transparency at the conclave stage will give rise to difficulties in the coronial, disciplinary and criminal arenas. PMID- 26821114 TI - Fluorofenidone attenuates bleomycin-induced pulmonary fibrosis by inhibiting eukaryotic translation initiation factor 3a (eIF3a) in rats. AB - Fluorofenidone is a novel derivative of l-mimosine. It has remarkable anti fibrotic properties. In this study, we established that fluorofenidone ameliorates pulmonary fibrosis (PF) both in vivo and in vitro by specifically inhibiting the expression of eukaryotic translation initiation factor 3a (eIF3a). eIF3a plays an important role in the development and progression of PF. An animal model of PF was induced by intratracheal instillation of bleomycin (5mg/kg) in rats. Rats were orally administered with fluorofenidone (250, 500 mg/kg/d.[i.g.]) and pirfenidone (500 mg/kg/d.[i.g.]) for 28 days. Primary pulmonary fibroblasts were cultured to determine the effect of fluorofenidone on TGF-beta1-induced (5 ng/ml) proliferation and differentiation of fibroblasts. The expression/level of eIF3a, TGF-beta1, alpha-SMA, collagen I, and collagen III were analyzed by ELISA, real-time PCR, and western blot. The cell proliferation rate was determined by MTS assay. The results indicate that fluorofenidone significantly improves the pathological changes in lung tissues and reduces the deposition of collagen by inhibiting eIF3a in rats with bleomycin-induced PF. Moreover, in a culture of pulmonary fibroblasts, fluorofenidone decreased the up-regulation of TGF-beta1 induced eIF3a by inhibiting the proliferation of cells and reducing the expression of alpha-SMA, collagen I, and collagen III. These findings suggest that eIF3a is a new and special target of fluorofenidone, which could be potentially used in the development of a drug that treats PF. PMID- 26821117 TI - Are NHE1 and inducible nitric oxide synthase involved in human ovarian cancer? PMID- 26821116 TI - Consumption of Bifidobacterium animalis subsp. lactis BB-12 impacts upper respiratory tract infection and the function of NK and T cells in healthy adults. AB - SCOPE: Probiotics can modulate immunity and reduce upper respiratory tract infections (URTI) in humans; however few studies have examined both outcomes in the same trial. The goal of the current study was to investigate the effect of Bifidobacterium animalis subsp. lactis BB-12, on natural killer (NK) and T-cell function in conjunction with self-reported cold/flu outcomes in healthy adults. METHODS AND RESULTS: In a randomized, partially blinded, four-period crossover study, healthy adults (n = 30) were recruited, and received four treatments for 4 weeks in a random order: (i) yogurt smoothies alone (YS); smoothies with BB-12 added (ii) before (PRE) or (iii) after (POST) yogurt fermentation, or (iv) BB-12 capsule (CAP). NK- and T-cell function was assessed at baseline and after each treatment. Incidence and severity of cold/flu infection was quantified using self reported URTI questionnaires. Participants on YS, PRE, or CAP treatments had elevated IL-2 secretion and NK-cell cytotoxicity, concurrently with fewer days with URTI. However, the POST treatment did not change immune outcomes or the severity of URTI. CONCLUSION: The timing of BB-12 addition to yogurt smoothies in relation to the fermentation process influenced the impact of BB-12 on immune function and cold/flu severity in young healthy adults. PMID- 26821119 TI - Forces and Kinetics of the Bacillus subtilis Spore Coat Proteins CotY and CotX Binding to CotE Inspected by Single Molecule Force Spectroscopy. AB - Spores are uniquely stable cell types that are produced when bacteria encounter nutrient limitations. Spores are encased in a complex multilayered coat, which provides protection against environmental insults. The spore coat of Bacillus subtilis is composed of around 70 individual proteins that are organized into four distinct layers. Here we explored how morphogenetic protein CotE guides formation of the outermost layer of the coat, the crust, around the forespore by focusing on three proteins: CotE, CotY, and CotX. Single molecule force spectroscopy (SMFS) was used to investigate the interactions among CotE, CotY, and CotX at the single-molecule level. Direct interactions among these three proteins were observed. Additionally, the dissociation kinetics was also studied by measuring the unbinding forces of the complexes at different loading rates. A series of kinetic data of these complexes were acquired. It was found that the interaction of CotE and CotY was stronger than that of CotE and CotX. PMID- 26821120 TI - Microglia PACAP and glutamate: Friends or foes in seizure-induced autonomic dysfunction and SUDEP? AB - Seizure-induced cardiorespiratory autonomic dysfunction is a major cause of sudden unexpected death in epilepsy (SUDEP), and the underlying mechanism is unclear. Seizures lead to increased synthesis, and release of glutamate, pituitary adenylate cyclase activating polypeptide (PACAP), and other neurotransmitters, and cause extensive activation of microglia at multiple regions in the brain including central autonomic cardiorespiratory brainstem nuclei. Glutamate contributes to neurodegeneration, and inflammation in epilepsy. PACAP has neuroprotective, and anti-inflammatory properties, whereas microglia are key players in inflammatory responses in CNS. Seizure-induced increase in PACAP is neuroprotective. PACAP produces neuroprotective effects acting on microglial PAC1 and VPAC1 receptors. Microglia also express glutamate transporters, and their expression can be increased by PACAP in response to harmful or stressful situations such as seizures. Here we discuss the mechanism of autonomic cardiorespiratory dysfunction in seizure, and the role of PACAP, glutamate and microglia in regulating cardiorespiratory brainstem neurons in their physiological state that could provide future therapeutic options for SUDEP. PMID- 26821118 TI - Recommendations for treating children with drug-resistant tuberculosis. AB - Tuberculosis (TB) is still one of the most difficult infectious diseases to treat, and the second most frequent cause of death due to infectious disease throughout the world. The number of cases of multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB), which are characterised by high mortality rates, is increasing. The therapeutic management of children with MDR- and XDR-TB is complicated by a lack of knowledge, and the fact that many potentially useful drugs are not registered for pediatric use and there are no formulations suitable for children in the first years of life. Furthermore, most of the available drugs are burdened by major adverse events that need to be taken into account, particularly in the case of prolonged therapy. This document describes the recommendations of a group of scientific societies on the therapeutic approach to pediatric MDR- and XDR-TB. On the basis of a systematic literature review and their personal clinical experience, the experts recommend that children with active TB caused by a drug-resistant strain of Mycobacterium tuberculosis should always be referred to a specialised centre because of the complexity of patient management, the paucity of pediatric data, and the high incidence of adverse events due to second-line anti-TB treatment. PMID- 26821121 TI - Bioglass promotes wound healing by affecting gap junction connexin 43 mediated endothelial cell behavior. AB - It is well known that gap junctions play an important role in wound healing, and bioactive glass (BG) has been shown to help healing when applied as a wound dressing. However, the effects of BG on gap junctional communication between cells involved in wound healing is not well understood. We hypothesized that BG may be able to affect gap junction mediated cell behavior to enhance wound healing. Therefore, we set out to investigate the effects of BG on gap junction related behavior of endothelial cells in order to elucidate the mechanisms through which BG is operating. In in vitro studies, BG ion extracts prevented death of human umbilical vein endothelial cells (HUVEC) following hypoxia in a dose dependent manner, possibly through connexin hemichannel modulation. In addition, BG showed stimulatory effects on gap junction communication between HUVECs and upregulated connexin43 (Cx43) expression. Furthermore, BG prompted expression of vascular endothelial growth factor and basic fibroblast growth factor as well as their receptors, and vascular endothelial cadherin in HUVECs, all of which are beneficial for vascularization. In vivo wound healing results showed that the wound closure of full-thickness excisional wounds of rats was accelerated by BG with reduced inflammation during initial stages of healing and stimulated angiogenesis during the proliferation stage. Therefore, BG can stimulate wound healing through affecting gap junctions and gap junction related endothelial cell behaviors, including prevention of endothelial cell death following hypoxia, stimulation of gap junction communication and upregulation of critical vascular growth factors, which contributes to the enhancement of angiogenesis in the wound bed and finally to accelerate wound healing. Although many studies have reported that BG stimulates angiogenesis and wound healing, this work reveals the relationship between BG and gap junction connexin 43 mediated endothelial cell behavior and elucidates one of the possible mechanisms through which BG stimulates wound healing. PMID- 26821122 TI - Decreasing child mortality, spatial clustering and decreasing disparity in North Western Burkina Faso. AB - Within relatively small areas, there exist high spatial variations of mortality between villages. In rural Burkina Faso, with data from 1993 to 1998, clusters of particularly high child mortality were identified in the population of the Nouna Health and Demographic Surveillance System (HDSS), a member of the INDEPTH Network. In this paper, we report child mortality with respect to temporal trends, spatial clustering and disparity in this HDSS from 1993 to 2012. Poisson regression was used to describe village-specific child mortality rates and time trends in mortality. The spatial scan statistic was used to identify villages or village clusters with higher child mortality. Clustering of mortality in the area is still present, but not as strong as before. The disparity of child mortality between villages has decreased. The decrease occurred in the context of an overall halving of child mortality in the rural area of Nouna HDSS between 1993 and 2012. Extrapolated to the Millennium Development Goals target period 1990 2015, this yields an estimated reduction of 54%, which is not too far off the aim of a two-thirds reduction. PMID- 26821123 TI - Substrate control for large area continuous films of monolayer MoS2 by atmospheric pressure chemical vapor deposition. AB - Growing monolayer MoS2 films that are continuous with large domain sizes by chemical vapor deposition is one of the major challenges in 2D materials research at the moment. Here, we explore how atmospheric pressure CVD can be used to grow centimeter scale continuous films of monolayer MoS2 films directly on Si substrates with an oxide layer whilst also obtaining large domain sizes exceeding 20 MUm within the films. This is achieved by orientating the growth substrate in a vertical position to improve the uniformity of precursor feed-stock compared to horizontally orientated growth substrates. This leads to continuous films of monolayer MoS2 over a significantly larger area without the need for low-pressure vacuum systems or volatile precursors. This provides important insights into novel approaches for maximizing domain sizes within MoS2 films, with concomitant large area uniform coverage. PMID- 26821124 TI - Preparation, optimization, characterization and in vivo pharmacokinetic study of asiatic acid tromethamine salt-loaded solid lipid nanoparticles. AB - PURPOSE: To enhance the oral bioavailability of asiatic acid tromethamine salt (AAS) by encapsulation in solid lipid nanoparticles (SLN). METHODS: The AAS loaded SLN (AASLN) was prepared by the modified solvent injection method with glycerin monostearate (GMS) as lipid and poloxamer 188 as surfactant. A Box Behnken design was used to optimize the formulations. Physicochemical characterization was carried out by using dynamic light scattering, scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Stabilities at 4 degrees C and pH 1.2 were investigated by particle size or/and entrapment efficiency (EE%). The in vivo pharmacokinetics was evaluated by HPLC-MS/MS. RESULTS: The optimal formulation of AASLN had an average size of 237 nm with zeta potential of -35.9 mV, and EE% of 64.4%. SEM showed that the AASLN had spherical shape with smooth surface. Furthermore, DSC and X-ray analyses indicated that AAS was amorphous state and the crystal degree of GMS was significantly decreased in the formulation. AASLN showed excellent stability at 4 degrees C for 1 month and no coacervation at pH 1.2. The bioavailability of AAS in SLN was found to be 2.5-fold higher than that of AAS alone after a single oral administration in rats. CONCLUSIONS: This study reveals that SLN is developed as a promising oral delivery system of AAS with significantly enhanced bioavailability and good storage stability. PMID- 26821126 TI - Pain Rules Are a Pain for Doctors. PMID- 26821127 TI - Message Received. PMID- 26821128 TI - Seizing Opportunity. PMID- 26821125 TI - Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin. AB - Integrins require an activation step prior to ligand binding and signaling. How talin and kindlin contribute to these events in non-hematopoietic cells is poorly understood. Here we report that fibroblasts lacking either talin or kindlin failed to activate beta1 integrins, adhere to fibronectin (FN) or maintain their integrins in a high affinity conformation induced by Mn(2+). Despite compromised integrin activation and adhesion, Mn(2+) enabled talin- but not kindlin-deficient cells to initiate spreading on FN. This isotropic spreading was induced by the ability of kindlin to directly bind paxillin, which in turn bound focal adhesion kinase (FAK) resulting in FAK activation and the formation of lamellipodia. Our findings show that talin and kindlin cooperatively activate integrins leading to FN binding and adhesion, and that kindlin subsequently assembles an essential signaling node at newly formed adhesion sites in a talin-independent manner. PMID- 26821129 TI - A Chance to Help. PMID- 26821130 TI - Going by the Book. PMID- 26821131 TI - Digital health revolution: perfect storm or perfect opportunity for pharmaceutical R&D? AB - The convergence of technology and medicine has pushed healthcare to the brink of a major disruption that pharma has, until recently, been slow to recognize. Tech players have pioneered the emerging field of digital wellness and health, and pharma is ideally placed to use its expertise in drug development and embrace these technologies to create digital applications that address major medical needs. This review describes digital innovation from a pharma R&D perspective, outlining principal drivers, digital components, opportunities and challenges as well as a sustainable new business model predicated on empowered patients and achieving therapeutic outcomes. PMID- 26821132 TI - DrugMiner: comparative analysis of machine learning algorithms for prediction of potential druggable proteins. AB - Application of computational methods in drug discovery has received increased attention in recent years as a way to accelerate drug target prediction. Based on 443 sequence-derived protein features, we applied the most commonly used machine learning methods to predict whether a protein is druggable as well as to opt for superior algorithm in this task. In addition, feature selection procedures were used to provide the best performance of each classifier according to the optimum number of features. When run on all features, Neural Network was the best classifier, with 89.98% accuracy, based on a k-fold cross-validation test. Among all the algorithms applied, the optimum number of most-relevant features was 130, according to the Support Vector Machine-Feature Selection (SVM-FS) algorithm. This study resulted in the discovery of new drug target which potentially can be employed in cell signaling pathways, gene expression, and signal transduction. The DrugMiner web tool was developed based on the findings of this study to provide researchers with the ability to predict druggable proteins. DrugMiner is freely available at www.DrugMiner.org. PMID- 26821133 TI - Challenges of glycosylation analysis and control: an integrated approach to producing optimal and consistent therapeutic drugs. AB - Glycosylation of therapeutic proteins has a profound impact on their safety and efficacy. Many factors shape the glycosylation of biotherapeutics, ranging from expression systems and cell culture processes to downstream purification strategies. Various analytical technologies have been developed to address questions concerning different aspects of glycosylation. Informatics tools are also crucial for a systematic understanding of the glycosylation processes. Hence, an integrated approach is required to harness glycosylation for the production of optimal and consistent glycoprotein-based therapeutic drugs. Here, we review the latest developments and challenges in glycosylation analysis and control in the context of bioprocessing monoclonal antibodies. PMID- 26821134 TI - Enforcing your IP rights. PMID- 26821135 TI - Drugging specific conformational states of GPCRs: challenges and opportunities for computational chemistry. AB - Current advances in structural biology for membrane proteins support the existence of multiple Gprotein-coupled receptor (GPCR) conformations. These conformations can be associated to particular receptor states with definite coupling and signaling capacities. Drugging such receptor states represents an opportunity to discover a new generation of GPCR drugs with unprecedented specificity. However, exploiting recently available structural information to develop these drugs is still challenging. In this context, computational structure-based approaches can inform such drug development. In this review, we examine the potential of these approaches and the challenges they will need to overcome to guide the rational discovery of drugs targeting specific GPCR states. PMID- 26821136 TI - Discovery of the First Environment-Sensitive Near-Infrared (NIR) Fluorogenic Ligand for alpha1-Adrenergic Receptors Imaging in Vivo. AB - Fluorescent ligands are gaining popularity as tools to aid GPCR research. Nonetheless, in vivo application of such tools is hampered due to their short excitation wavelengths in the visible range and lack of fluorogenic switch. Here we report the discovery of fluorescent ligands (3a-f) for alpha1-adrenergic receptors (alpha1-ARs) by conjugating the environment-sensitive fluorophore cyane 5 (Cy5) with the quinazoline pharmacophore. Among them, the conjugated compound 3a, with acylated piperazine and the shortest carbon chain spacer, exhibited potent binding and remarkable changes in fluorescence (10-fold) upon binding to alpha1-AR. Furthermore, it could be employed to selectively and specifically label alpha1-ARs with no washing procedures in single cells, prostate tissue slices, intact tumor xenografts and organs in living mice. Especially, the slice imaging results gave direct and visual evidence that there is a close relationship between alpha1-ARs and pathological prostate. It is anticipated that our fluorescent tools will find broad applications in the study of alpha1-AR pharmacology and physiology to aid development of novel therapeutics. PMID- 26821138 TI - Erratum to: A retrospective study on the outcomes of posterior-only vertebral column resection in treating patients with severe isolated congenital kyphosis: more than 2 years follow-up in a single center. PMID- 26821140 TI - Sequential alignment change of the cervical spine after anterior cervical discectomy and fusion in the lower cervical spine. AB - PURPOSE: The cervical spine has a linear chain of correlation or reciprocal relationship regionally (within the cervical spine) and globally (head to whole spine). The purpose of this study was to assess the sequential alignment change of the regional and global cervical spine after two-level anterior cervical discectomy and fusion (ACDF) performed on the lower cervical spine. METHODS: This study included 61 patients (mean age 56 +/- 8.6 years; range 35-70 years) who underwent ACDF at C5-6-7 with a plate-cage construct and whose C-spine neutral lateral radiographs showed an identical degree of horizontal gaze (occipital slope) peri-operatively. We compared the change in cervical curvature from the occiput to C7 with the absolute value (slope angle) and relative value (between two different slopes). We also investigated the correlated change in multiple angular parameters according to the change in the occipital slope. RESULTS: The occipital slope was significantly correlated with the value of the C1-slope (r = 0.33) and C2- slope (r = 0.51). The value of the center of the sellar turcica-C7 sagittal vertical axis (St-SVA) was very closely related to the C1-slope (r = 0.83), C2-slope (r = -0.8), C2-7 angle (r = -0.43), and C2-5 angle (r = -0.46). The amount of angular change at the surgical level (C5-7A) was 5.8 degrees (2.9 degrees -> 8.5 degrees ), and the sum of the change in the C5-slope and C7-slope was 6 degrees (3.1 degrees + 2.9 degrees ). In general, the C2-5 angle decreased about 3 degrees , in proportion to the upward inclination of C5-slope (3.1 degrees ), because the C2-slope was fixed. However, patients who showed improvement in cervical alignment (greatly increased C5-7 lordosis or greatly decreased St-SVA after surgery) often had upper cervical slope change (C1-s and C2-s). CONCLUSIONS: The ACDF procedure itself can induce regional slope change (C5-s and C7-s) directly at the surgical level and can also influence upper cervical slope change (C1-s and C2s) indirectly. Then the change in the upper cervical spine can induce a change in the St-CVA and spino-cranial angle (SCA). PMID- 26821139 TI - A case study of occipital outgrowth: a rare suboccipital abnormality. AB - PURPOSE: To describe the clinical and radiological characteristics of uncommon upper cervical spine abnormality in children. METHODS: Clinical and diagnostic characteristics of three patients aged 6-12 years with a similar uncommon type of occipital anomaly are described. The patients were admitted in 2007, 2009, and 2014, respectively. RESULTS: All patients were clinically and radiologically examined. In each case the massive, additional unilateral outgrowth of the occipital bone (os occipitale) was visualized. The signs and symptoms included torticollis, acute brain ischemia, and limited head motion. Two of the three patients underwent surgical treatment: an occipital-cervical fusion was performed in the first patient, and the outgrowth was removed in the second patient. After 1 year of follow-up the results were estimated as good for both patients, with better functional outcome for the second patient. The parents of the third patient did not consent for the surgical treatment. CONCLUSIONS: The unique features of this abnormality distinguish it from previous descriptions of the manifestation of pro-atlas, atlas, or atlanto-occipital synostosis. The presented abnormality had different manifestation of various severity in each case, from torticollis to acute vascular disorder. STUDY DESIGN: Clinical case series. LEVEL OF EVIDENCE: IV. PMID- 26821141 TI - Laminar closure rates in patients with cervical myelopathies treated with either open-door laminoplasty with reattachment of spinous processes and extensor musculature or Hirabayashi open-door laminoplasty: a case-control study. AB - PURPOSE: The presence of preoperative kyphosis has been identified as a risk factor for laminar closure (LC). We have been performing modified open-door laminoplasty with reattachment of the spinous processes and extensor musculature for patients with reduced cervical lordosis because this procedure can prevent progression of cervical kyphosis. This procedure may also prevent LC. The purpose of this study was to evaluate the rate of LC after the modified open-door laminoplasty. METHODS: A total of 104 patients who underwent open-door laminoplasty were retrospectively reviewed. Of these patients, 18 underwent modified open-door laminoplasty (group M), whereas the other 86 underwent Hirabayashi open-door laminoplasty (group H). Group H was divided into two classes according to the preoperative cervical lordosis angle (group H1 <= 10 degrees vs. group H2 >= 11 degrees ). All 18 patients in group M had a preoperative lordosis angle <=10 degrees . The outcomes were assessed using the rate of LC, the cross-sectional area (CSA) of the erector muscle on magnetic resonance imaging, and the Japanese Orthopaedic Association score (JOA score). RESULTS: The rate of laminar closure was significantly lower in group M (39 %) than in group H1 (76 %) (P < 0.01). The CSAs tended to be larger in the muscle preservation side of group M than in the other groups. There was no significant difference in the JOA score among the three groups. CONCLUSIONS: Although patients with decreased cervical lordosis have a higher risk of LC, the results suggested that modified open-door laminoplasty could reduce the rate of LC compared with Hirabayashi open-door laminoplasty. PMID- 26821142 TI - Morphometric features of posterior cranial fossa are different between Chiari I malformation with and without syringomyelia. AB - PURPOSE: To investigate whether the posterior cranial fossa (PCF) morphology in Chiari I malformation without syringomyelia (also called syrinx) (CMI-only) is different from that in Chiari I malformation with syrinx (CMI-S). METHODS: Nineteen CMI patients without syrinx constituted the CMI-only group, whereas 48 CMI patients with syrinx were assigned to the CMI-S group. Another cohort of 40 age-matched asymptomatic adolescents was enrolled to serve as the control group. Six measurements were evaluated and compared between these three groups from T1 weighted magnetic resonance (MR) imaging, including the length of the clivus (AB), the anteroposterior diameter of the foramen magnum (BC), the length of the supraocciput (CD), the anteroposterior diameter of the posterior fossa (DA), the posterior fossa height (BE) and the clivus gradient ([Formula: see text]). The posterior cranial fossa morphology in relation to syrinx severity was also investigated. RESULTS: Compared to the normal controls, the AB, CD, DA, BE and [Formula: see text] were significantly larger in the CMI-S group. Similar changes in AB, CD, DA and BE were also demonstrated in the CMI-only group, while the clivus gradient ([Formula: see text]) was found to be normal when compared with the control group. A significantly decreased clivus gradient was observed in the CMI-S group as compared to CMI-only group. In addition, the clivus was significantly flattened in patients with a distended-syrinx in comparison to those with a non-distended syrinx. CONCLUSIONS: Small size of the posterior fossa was detected both in CMI cases with and without syrinx. The clivus gradient served as the only morphologic difference in the PCF between CMI-S and CMI-only patients and was correlated with the severity of the syrinx, may support the theory that the restricted circulation of cerebrospinal fluid at the anterior paramedial subarachnoid space contributes to the formation of a syrinx. PMID- 26821143 TI - A decision analysis to identify the ideal treatment for adult spinal deformity: is surgery better than non-surgical treatment in improving health-related quality of life and decreasing the disease burden? AB - BACKGROUND: Adult spinal deformity (ASD) is a major public health problem. There are pros and cons of the available treatment alternatives (surgical or non surgical) and it had been difficult to identify the best treatment modality. AIM: To construct a statistical DA model to identify the optimum overall treatment in ASD. METHODS: From an international multicentre database of ASD patients (968 pts), 535 who had completed 1 year follow-up (371 non-surgical-NS, 164 surgical S), constitute the population of this study. DA was structured in two main steps of: (1) baseline analysis (assessing the probabilities of outcomes, assessing the values of preference-utilities-, combining information on probability and utility and assigning the quality adjusted life expectancy (QALE) for each treatment) and (2) sensitivity analysis. RESULTS: Four hundred and thirty-two patients (309 NS, 123 S) had baseline and 1 year follow-up ODI measurements. Overall, 104 (24.1 %) were found to be improved (a decrease in ODI > 8 points), 225 (52.1 %) unchanged (-8 > ODI > 8) and 65 deteriorated. Surgery presented with a higher chance of improvement (54.2 %) versus NS (9.7 %). The overall QALE ranged from 56 to 69 (of 100 years) and demonstrated better final QALE in the NS group (60 vs. 65, P = 0.0038), this group having started with higher QALE as well (56 vs. 65 years, P < 0.0001). There were improvements in overall QALE in both groups but this was significant only in the surgical group (S from 56 to 60 years, P < 0.0001; NS from 65 to 65 years, P = 0.27). In addition, in the subgroup of patients with significant baseline disability (ODI > 25) surgery appeared to yield marginally better final QALE (58 vs. 56 years, P = 0.1) despite very a similar baseline (54 vs. 54 years, P = 0.93). DISCUSSION AND CONCLUSIONS: This study demonstrated that a single best treatment modality for ASD may not exist. Conservative treatment appears to yield higher (up to 6 %) QALE compared to surgery, most probably secondary to a higher baseline QALE. On the other hand, surgery provides a significantly higher increase in QALE. Especially in patients with significant disability at baseline, the final QALE tended higher in the S group (although not significant). Finally, chances of a relevant improvement at first year turned out to be significantly lower with NS treatment. PMID- 26821146 TI - Template method to controllable synthesis 3D porous NiCo2O4 with enhanced capacitance and stability for supercapacitors. AB - We present a facile template method to fabricate NiCo2O4 (NCO) composites with 3D porous structure as electrodes for supercapacitors. SiO2 sol is used as the template to prevent the aggregation of NCO and construct the porous structure with high specific surface area. Meanwhile, the binary metal oxides not only inherit the merits of single nickel oxides or cobalt oxides, but also show superior properties to promote the capacitance. The uniform structure of NCO12 (SiO2/NCO=1:2) is obtained through controlling the mass ratio of SiO2 and NCO. Owing to the dual advantages of porous structure and binary system, NCO12 composites exhibit highly enhanced electrochemical performance compared with those of directly prepared NCO, NCO21 (SiO2/NCO=1:0.5) and NCO14 (SiO2/NCO=1:4). The specific capacitance of NCO12 composite is about 1389 Fg(-1) at 1 Ag(-1). At 4 Ag(-1), the capacitance is still as high as 1090 Fg(-1) together with capacitance retention of 80% over 2500 cycles. The capacitance and stability are higher than those of most previously reported pure NCO composites, which make it a very promising electrode material for energy storage. PMID- 26821144 TI - Calcific discitis with giant thoracic disc herniations in adults. AB - PURPOSE: Calcific discitis is a self-limiting process most commonly seen in the cervical spine of children. Rare literature exists regarding the natural history and management of this condition in adults, especially when it presents as a giant thoracic disc herniation into the spinal canal. Giant herniations in the thoracic spine are typically surgically removed to reduce the chance of permanent neurologic deficit from spinal cord compression. However, when associated with calcific discitis, they may undergo spontaneous regression with the need for surgery obviated. METHODS: Medical records and radiographic studies of two adult patients with calcific discitis and myelopathy due to spinal cord compression by giant thoracic disc herniations were retrospectively reviewed. Search of the literature on calcific discitis in adults and spontaneous regression of calcified thoracic disc herniations was separately performed. RESULTS: Both patients were young male adults presenting with back pain and early signs of myelopathy. With restriction of activities and oral NSAIDs, their symptoms were relieved within 3 months. Four adult cases of calcific discitis (characteristic central calcification confined within the nucleus pulposus) and three instances of spontaneous regression of small- to medium-sized thoracic calcified disc herniations were identified from the literature. CONCLUSIONS: The demonstration of spontaneous resorption of giant calcified thoracic disc herniations in two adult patients with calcific discitis supplements the existing literature and provides the first evidence that giant calcified thoracic disc herniations may still undergo spontaneous remission and a "wait and watch" strategy may be justified at least in the initial management of these patients, even with the presence of mild myelopathy. PMID- 26821145 TI - Thoracic sagittal plane variations between patients with thoracic adolescent idiopathic scoliosis and healthy adolescents. AB - PURPOSE: To analyze the sagittal thoracic parameters of different types of progressive thoracic adolescent idiopathic scoliosis (AIS) patients and compare them with healthy adolescents. METHODS: 115 AIS patients with main thoracic curves (Cobb: 59.4 +/- 12.7) were prospectively compared with 116 healthy adolescents. The AIS and control (C) groups were homogeneous in terms of age and gender. Standing sagittal radiographs were analyzed for differences in T5-T12 kyphosis, T5-T8 and T9-T12 segmental kyphosis, the change between these two angles, and the double rib contour sign. Statistical analyses were performed using the chi 2, one-way ANOVA, Mann-Whitney U and Student's t tests. RESULTS: The sagittal parameters of Lenke 1 curves did not differ from healthy adolescents (T5-T8: 17.1 +/- 10 vs C: 16 +/- 7; T9-T12: 6.3 +/- 7 vs C: 7.9 +/- 5; T5-T12: 23.9 +/- 14 vs C: 23.9 +/- 8). Compared with the controls, Lenke type 3 curves were globally more hypokyphotic (T5-T12: 18.9 +/- 12 vs C: 23.9 +/- 8, P = 0.027) due to a "lordosis" of the lower thoracic segment (T9-T12: 0.9 +/- 10 vs C: 7.9 +/- 5, P = 0.001). Type 2 curves tended to exhibit more pronounced upper thoracic kyphosis (T5-T8: 20.7 +/- 12 vs C: 16 +/- 7). Both types 2 and 3 require a marked TK changes in the transition between the upper and lower thoracic segments to compensate for global (T5-T12) kyphosis. CONCLUSIONS: In this 2D analysis of moderate AIS, Lenke 1 curves exhibited normal thoracic sagittal parameters, which brings into question the effect of lordosis on the development of single thoracic curves. Lenke 3 curves exhibited lower thoracic segmental hypokyphosis, and the type 2 showed upper segmental hyperkyphosis. These results should be considered when planning a surgical strategy. PMID- 26821147 TI - Spreading, encapsulation and transition to arrested shapes during drop impact onto hydrophobic powders. AB - We present findings from an experimental study of the impact of liquid droplets onto powder surfaces, where the particulates are hydrophobic. We vary both the size of the drop and impact speed coupled with the size range of the powder in order to assess the critical conditions for the formation of liquid marbles, where the drop becomes completely encapsulated by the powder, and arrested shapes where the drop cannot regain its spherical shape. By using different hydrophobization agents we find that a lower particle mobility may aid in promoting liquid marble formation at lower impact kinetic energies. From observations of the arrested shape formations, we propose that simple surface tensions may be inadequate to describe deformation dynamics in liquid marbles. PMID- 26821148 TI - Wetting hysteresis induced by temperature changes: Supercooled water on hydrophobic surfaces. AB - The state and stability of supercooled water on (super)hydrophobic surfaces is crucial for low temperature applications and it will affect anti-icing and de icing properties. Surface characteristics such as topography and chemistry are expected to affect wetting hysteresis during temperature cycling experiments, and also the freezing delay of supercooled water. We utilized stochastically rough wood surfaces that were further modified to render them hydrophobic or superhydrophobic. Liquid flame spraying (LFS) was utilized to create a multi scale roughness by depositing titanium dioxide nanoparticles. The coating was subsequently made non-polar by applying a thin plasma polymer layer. As flat reference samples modified silica surfaces with similar chemistries were utilized. With these substrates we test the hypothesis that superhydrophobic surfaces also should retard ice formation. Wetting hysteresis was evaluated using contact angle measurements during a freeze-thaw cycle from room temperature to freezing occurrence at -7 degrees C, and then back to room temperature. Further, the delay in freezing of supercooled water droplets was studied at temperatures of -4 degrees C and -7 degrees C. The hysteresis in contact angle observed during a cooling-heating cycle is found to be small on flat hydrophobic surfaces. However, significant changes in contact angles during a cooling-heating cycle are observed on the rough surfaces, with a higher contact angle observed on cooling compared to during the subsequent heating. Condensation and subsequent frost formation at sub-zero temperatures induce the hysteresis. The freezing delay data show that the flat surface is more efficient in enhancing the freezing delay than the rougher surfaces, which can be rationalized considering heterogeneous nucleation theory. Thus, our data suggests that molecular flat surfaces, rather than rough superhydrophobic surfaces, are beneficial for retarding ice formation under conditions that allow condensation and frost formation to occur. PMID- 26821149 TI - Nickel nanoparticles with hcp structure: Preparation, deposition as thin films and application as electrochemical sensor. AB - Hexagonal close packed (hcp) nickel nanoparticles stabilized by polyvinylpyrrolidone (PVP) were synthesized through the thermal treatment of face centered cubic (fcc) nickel nanoparticles. Controlling both the temperature of the heat treatment and the amount of PVP was possible the control of the hcp/fcc rate in the samples, where the higher Ni/PVP ratio produces only the hcp-nickel phase (average size of 8.9 nm) highly stable in air. The crystalline structure, the presence of PVP, the size of the nanoparticles and the stability of the hcp nickel were confirmed using X-ray diffractometry, Fourier transform infrared spectroscopy, transmission electron microscopy, Raman spectroscopy, scanning electron microscopy and thermogravimetric analysis. Thin films of hcp and fcc nickel nanoparticles were prepared through a biphasic system and deposited over indium-doped tin oxide (ITO) substrates, which were electrochemically characterized and applied as glycerol amperometric sensors in NaOH medium. Parameters as the number of cycles applied and the scan rate were evaluated and indicate that hcp nickel nanoparticles are more reactive to form Ni(OH)2 and lead to more electroactive Ni(OH)2 structure. The hcp nickel nanoparticles-modified electrode showed the best sensitivity (0.258 MUA L MUmol(-1)) and detection limit (2.4 MUmol L(-1)) toward glycerol. PMID- 26821137 TI - Total medical costs of treating femoral neck fracture patients with hemi- or total hip arthroplasty: a cost analysis of a multicenter prospective study. AB - The aim of this study was to determine the total medical costs for treating displaced femoral neck fractures with hemi- or total hip arthroplasty in fit elderly patients. The mean total costs per patient at 2 years of follow-up were ?26,399. These results contribute to cost awareness. INTRODUCTION: The absolute number of hip fractures is rising and increases the already significant burden on society. The aim of this study was to determine the mean total medical costs per patient for treating displaced femoral neck fractures with hemi- or total hip arthroplasty in fit elderly patients. METHODS: The population was the Dutch sample of an international randomized controlled trial consisting of femoral neck fracture patients treated with hemi- or total hip arthroplasty. Patient data and health care utilization were prospectively collected during a total follow-up period of 2 years. Costs were separated into costs for hospital care during primary stay, hospital costs for clinical follow-up, and costs generated outside the hospital during rehabilitation. Multiple imputations were used to account for missing data. RESULTS: Data of 141 participants (mean age 81 years) were included in the analysis. The 2-year mortality rate was 19 %. The mean total cost per patient after 10 weeks of follow-up was ?15,216. After 1 and 2 years of follow-up the mean total costs were ?23,869 and ?26,399, respectively. Rehabilitation was the main cost determinant, and accounted for 46 % of total costs. Primary hospital admission days accounted for 22 % of the total costs, index surgery for 11 %, and physical therapy for 7 %. CONCLUSIONS: The main cost determinants for hemi- or total hip arthroplasty after treatment of displaced femoral neck fractures (?26,399 per patient until 2 years) were rehabilitation and nursing homes. Most of the costs were made in the first year. Reducing costs after hip fracture surgery should focus on improving the duration and efficiency of the rehabilitation phase. PMID- 26821151 TI - The microbiome and atopic eczema: More than skin deep. AB - Discoveries in the defective molecular composition of the epidermal barrier, such as the epidermal protein filaggrin, in those with atopic eczema (or atopic dermatitis [AD]) have proved crucial in understanding this disease, but its aetiology remains to be fully elucidated. The epidermal barrier is just one interface between the microbial world and our immune system. Recent advances in molecular technology have demonstrated for the first time the true scale of the normal human microbiome and changes seen in disease states. In this review article we discuss the role of the human microbiome in the aetiology and maintenance of AD. The role of Staphylococcus aureus within the skin microbiome is examined, in addition to the role of other bacteria and fungi, identified using novel culture-independent methods. The significant contribution of the gut microbiome and its manipulation via probiotic use is also reviewed. We emphasise that the microbiome of separate systems, including the gut, has a significant role to play in the manifestation of this cutaneous disorder. To date, there has been a lack of studies investigating whether changes to the lung microbiome may play a role in AD. An early interaction between the microbiome and immune system via multiple routes (skin-gut-lung) could feasibly affect the risk of a subsequent development of atopic diseases. When making management decisions for AD patients, clinicians must be mindful of the role of the microbiome. PMID- 26821150 TI - Long-Term Outcomes of Patients with Acute Cholecystitis after Successful Percutaneous Cholecystostomy Treatment and the Risk Factors for Recurrence: A Decade Experience at a Single Center. AB - BACKGROUND: Percutaneous cholecystostomy tube (PCT) has been effectively used for the treatment of acute cholecystitis (AC) for patients unsuitable for early cholecystectomy. This retrospective study investigated the recurrence rate after successful PCT treatment and factors associated with recurrence. METHODS: We reviewed patients treated with PCT for AC from October 2004 through December 2013. Patients with successful PCT treatment were those who were free from persistent PCT drainage. We used multivariable logistic regression analysis sequentially to identify factors associated with each outcome. RESULTS: The study included 184 patients (mean age: 70.1 years). The average duration for parenteral antibiotics was 14.4 days and 20.0 days for PCT drainage. The one-year recurrence rate was 9.2% (17/184) with most recurrences occurring within two months (6.5%, 12/184) of the procedure. Complicated cholecystitis (odds ratio [OR]: 4.67; 95% confidence interval [CI]: 1.44-15.70; P = 0.01) and PCT drainage duration >32 days (OR: 4.92; 95% CI: 1.03-23.53; P = 0.05) positively correlated with one-year recurrence; parenteral antibiotics duration >10 days (OR: 0.21; 95% CI: 0.05 0.68; P = 0.01) was inversely associated with one-year recurrence. CONCLUSIONS: The recurrence rate was low for patients after successful PCT treatment. Predictors for recurrence included the severity of initial AC and subsequently provided treatments. PMID- 26821152 TI - Kaempferol as Selective Human MAO-A Inhibitor: Analytical Detection in Calabrian Red Wines, Biological and Molecular Modeling Studies. AB - The purpose of this work was to determine the kaempferol content in three red wines of Calabria, a southern Italian region with a great number of certified food products. Considering that wine cultivar, climate, and soil influence the qualitative and quantitative composition in flavonoids of Vitis vinifera L. berries, the three analyzed samples were taken from the 2013 vintage. Moreover, the Gaglioppo samples, with assigned Controlled Origin Denomination (DOC), were also investigated in the production of years 2008, 2010, and 2011. In addition to the analysis of kaempferol, which is present in higher concentration than in other Italian wines, in vitro assays were performed to evaluate, for the first time, the inhibition of the human monoamine oxidases (hMAO-A and hMAO-B). Molecular recognition studies were also carried out to provide insight into the binding mode of kaempferol and selectivity of inhibition of the hMAO-A isoform. PMID- 26821153 TI - Altered Expression of Cytoskeletal and Axonal Proteins in Oxaliplatin-Induced Neuropathy. AB - BACKGROUND: Oxaliplatin is a platinum compound widely used in the treatment of some solid tumors. Despite its usefulness, oxaliplatin-associated neurotoxicity represents the main dose-limiting factor of this drug. This study examined the structural neuronal effects of oxaliplatin treatment in spinal and supraspinal levels. METHODS: Protein expression was investigated in the mouse cortex, thalamus, periaqueductal grey (PAG) matter and spinal cord (SC) by Western blotting. Thermal nociception was assessed by the hot plate test. RESULTS: Results indicate a reduction in the levels of growth associated protein-43 (GAP43) in the cortex and SC areas at the end of thermal hyperalgesic response, while a decrease in neurofilament-H (NfH) phosphorylation was observed in the SC on day 21 when the pain-related manifestation reaches the neurotoxic peak. Counteracting phosphorylated NfH content increases in the SC and cortex regions at day 28 as a result of the beginning of neuro-regeneration process. We also revealed that the levels of HuD, a neuronal-specific RNA-binding protein, decreased, demonstrating the same temporal and regional expression pattern of GAP43. Oxaliplatin chronic treatment induced a region-specific upregulation of gamma isoform of protein kinase C (PKC) within thalamus and PAG, and the administration of a PKC inhibitor suggests that PKC activity in these brain regions must be required to maintain the thermal hyperalgesic state. CONCLUSIONS: These results suggest that changes in the protein levels of the regulatory and structural proteins are due to oxaliplatin-induced neurotoxicity and imply that there is a direct link between structural changes in the central nervous system and chemotherapy-induced neurotoxicity. PMID- 26821155 TI - Prior Design for Dependent Dirichlet Processes: An Application to Marathon Modeling. AB - This paper presents a novel application of Bayesian nonparametrics (BNP) for marathon data modeling. We make use of two well-known BNP priors, the single-p dependent Dirichlet process and the hierarchical Dirichlet process, in order to address two different problems. First, we study the impact of age, gender and environment on the runners' performance. We derive a fair grading method that allows direct comparison of runners regardless of their age and gender. Unlike current grading systems, our approach is based not only on top world records, but on the performances of all runners. The presented methodology for comparison of densities can be adopted in many other applications straightforwardly, providing an interesting perspective to build dependent Dirichlet processes. Second, we analyze the running patterns of the marathoners in time, obtaining information that can be valuable for training purposes. We also show that these running patterns can be used to predict finishing time given intermediate interval measurements. We apply our models to New York City, Boston and London marathons. PMID- 26821157 TI - Treatment of striae distensae with needling therapy versus CO2 fractional laser. AB - BACKGROUND AND OBJECTIVES: Striae are atrophic dermal scars with overlying epidermal atrophy causing cosmetic concern. This study assesses and compares the efficacy and safety of needling therapy versus CO2 fractional laser in treatment of striae. METHODS: Twenty Egyptian female patients with striae in the abdomen and lower limbs were involved in the study. The patients were treated with needling therapy and CO2 laser every 1 month for 3 sessions. Follow-up by digital photography and skin biopsy was conducted at baseline and 6 months after treatment. Clinical improvement was assessed by comparing photographs and patient's satisfaction before and after treatment. RESULTS: Nine of 10 (90%) needle-treated patients showed improvement. Among them, 3 (30%) had good, 4 (40%) had fair, and 2 (20%) had poor improvements; however, 1 (10%) did not show any improvement after the treatment. In CO2-laser treated patients, 5 of 10 (50%) of the patients showed clinical improvement; 1 (10%) were good, 3 (30%) were fair, and 1 (10%) were poor; however, 5 (50%) did not show improvement. CONCLUSION: The results support the use of microneedle therapy over CO2 lasers for striae treatment. PMID- 26821156 TI - Phase II study of oral vitamin B12 supplementation as an alternative to intramuscular injection for patients with non-small cell lung cancer undergoing pemetrexed therapy. AB - PURPOSE: A vitamin B12 supplement is required in pemetrexed single agent therapy. Intramuscular administration is the method of choice; however, oral administration is simpler and easier and may be sufficiently effective. We conducted a Phase II study to evaluate the safety of oral administration of vitamin B12 in patients with advanced non-small cell lung cancer who received pemetrexed single agent therapy. METHODS: Folic acid and vitamin B12 were given orally for ? 1 week before pemetrexed administration. The primary end-point was onset of a grade >= 3 neutropenia ratio (50% of threshold expression ratios; an expectation expression ratio of 21%; alpha, 0.05; beta, 0.1). Blood concentration of folic acid and homocysteine which are markers of vitamin B12 deficiency were also examined (UMIN000003180). RESULTS: A total of 25 cases were registered from February 2010 to July 2014. The ratio of grade >= 3 neutropenia was 36% (95% CI 22-52 %). Grade >= 3 non-hematologic toxicity and hematologic toxicity were seen in 20% (5 cases) and 44% (11 cases) of patients, respectively. In addition, the homocysteine blood concentration just before the first cycle dosage of pemetrexed was significantly elevated relative to the 2-3 cycle. CONCLUSION: This study failed to meet its primary endpoint. We could not demonstrate the safety and efficacy of the 1-week vitamin B12 oral administration protocol as compared with intramuscular administration. PMID- 26821154 TI - Effectiveness and Safety of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B: A 3-Year, Prospective, Real-World Study in France. AB - BACKGROUND AND AIMS: Tenofovir disoproxil fumarate (TDF) demonstrated potent and sustainable antiviral efficacy and a good safety profile in patients with chronic hepatitis B (CHB) in controlled clinical trials. Real-world data are important to confirm effectiveness and safety data in patient populations encountered in routine clinical practice. METHODS: This non-interventional, prospective, 36 month study included treatment-naive and treatment-experienced patients with CHB initiating their first TDF regimen (monotherapy or combination therapy) in routine clinical practice in France. Clinical, virologic, biochemical, compliance, and safety data were collected. RESULTS: Data from 440 consecutive patients from 58 centers were analyzed. The majority of the cohort was male (71 %), hepatitis B "e" antigen-negative (HBeAg-) (74 %), and treatment-experienced (56 %); 11 % were aged >=65 years; and comorbidities were reported in 39 %. After 12 months, 92 % of the overall cohort achieved virologic response (HBV DNA <69 IU/mL) which was maintained to 36 months (96 %); virologic response was achieved by >90 % of patients irrespective of HBeAg status, age, or prior treatment history. At 36 months, 77 % of patients had normal alanine aminotransferase levels. Fourteen patients lost hepatis B surface (HBs) antigen, and seven seroconverted to anti-HBs. TDF was well tolerated over the 36-month study, including in 14 women who became pregnant during the study. Median estimated glomerular filtration rate did not change markedly from baseline irrespective of prior treatment history. CONCLUSIONS: TDF demonstrated potent virologic and biochemical responses across a broad range of patients reflective of routine clinical practice. The safety profile was consistent with results from pivotal trials. PMID- 26821158 TI - Association between Metabolic Syndrome and Bone Mineral Density--Data from the Berlin Aging Study II (BASE-II). AB - BACKGROUND: Decreased bone mineral density (BMD) has been linked to metabolic disorders, such as type 2 diabetes. However, results regarding the metabolic syndrome (MetS), a cluster of at least 3 of 5 cardiovascular risk parameters with potentially contradictory effects on BMD are still inconclusive. OBJECTIVE: We investigated the effect of MetS and its single parameters on BMD at 3 sites in community-dwelling older subjects. METHODS: 1,402 subjects (51.1% female, 68 +/- 4 years old) from the Berlin Aging Study II (BASE-II) were included. MetS was defined as suggested by IDF/NHLBI/AHA. Insulin resistance (IR) was assessed by the homeostasis model of IR. BMD (lumbar spine, femur neck, hip) and trunk fat were measured by dual-energy X-ray absorptiometry. Osteoporosis was defined by a T score of <=-2.5. RESULTS: MetS was present in 29.6% of women and 41.7% of men. In regression models, we observed a positive association of MetS with the BMD of the lumbar spine (p = 0.005) and hip (p = 0.028) in women even after adjustment for risk factors, but no effect of the single parameters apart from IR. In contrast, there was no association between MetS and BMD in men. However, higher trunk fat and higher waist circumference were associated with lower levels of BMD in men with or without MetS (p < 0.05). CONCLUSION: We obtained different results in men and women. In women, the positive though slight effect of MetS on BMD could not be explained by single MetS components apart from IR. In men, central obesity was negatively associated with BMD, suggesting that the metabolic effects driven by visceral fat have a negative impact. PMID- 26821159 TI - The Ancestral Carnivore Karyotype As Substantiated by Comparative Chromosome Painting of Three Pinnipeds, the Walrus, the Steller Sea Lion and the Baikal Seal (Pinnipedia, Carnivora). AB - Karyotype evolution in Carnivora is thoroughly studied by classical and molecular cytogenetics and supplemented by reconstructions of Ancestral Carnivora Karyotype (ACK). However chromosome painting information from two pinniped families (Odobenidae and Otariidae) is noticeably missing. We report on the construction of the comparative chromosome map for species from each of the three pinniped families: the walrus (Odobenus rosmarus, Odobenidae-monotypic family), near threatened Steller sea lion (Eumetopias jubatus, Otariidae) and the endemic Baikal seal (Pusa sibirica, Phocidae) using combination of human, domestic dog and stone marten whole-chromosome painting probes. The earliest karyological studies of Pinnipedia showed that pinnipeds were characterized by a pronounced karyological conservatism that is confirmed here with species from Phocidae, Otariidae and Odobenidae sharing same low number of conserved human autosomal segments (32). Chromosome painting in Pinnipedia and comparison with non-pinniped carnivore karyotypes provide strong support for refined structure of ACK with 2n = 38. Constructed comparative chromosome maps show that pinniped karyotype evolution was characterized by few tandem fusions, seemingly absent inversions and slow rate of genome rearrangements (less then one rearrangement per 10 million years). Integrative comparative analyses with published chromosome painting of Phoca vitulina revealed common cytogenetic signature for Phoca/Pusa branch and supports Phocidae and Otaroidea (Otariidae/Odobenidae) as sister groups. We revealed rearrangements specific for walrus karyotype and found the chromosomal signature linking together families Otariidae and Odobenidae. The Steller sea lion karyotype is the most conserved among three studied species and differs from the ACK by single fusion. The study underlined the strikingly slow karyotype evolution of the Pinnipedia in general and the Otariidae in particular. PMID- 26821160 TI - Plant-Mediated Synthesis of Silver Nanoparticles: Their Characteristic Properties and Therapeutic Applications. AB - Interest in "green nanotechnology" in nanoparticle biosynthesis is growing among researchers. Nanotechnologies, due to their physicochemical and biological properties, have applications in diverse fields, including drug delivery, sensors, optoelectronics, and magnetic devices. This review focuses on the green synthesis of silver nanoparticles (AgNPs) using plant sources. Green synthesis of nanoparticles is an eco-friendly approach, which should be further explored for the potential of different plants to synthesize nanoparticles. The sizes of AgNPs are in the range of 1 to 100 nm. Characterization of synthesized nanoparticles is accomplished through UV spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, and scanning electron microscopy. AgNPs have great potential to act as antimicrobial agents. The green synthesis of AgNPs can be efficiently applied for future engineering and medical concerns. Different types of cancers can be treated and/or controlled by phytonanotechnology. The present review provides a comprehensive survey of plant mediated synthesis of AgNPs with specific focus on their applications, e.g., antimicrobial, antioxidant, and anticancer activities. PMID- 26821162 TI - Pearls: Avoiding Bad Slides. PMID- 26821161 TI - The Story of a Hitchhiker: Population Genetic Patterns in the Invasive Barnacle Balanus(Amphibalanus) improvisus Darwin 1854. AB - Understanding the ecological and evolutionary forces that determine the genetic structure and spread of invasive species is a key component of invasion biology. The bay barnacle, Balanus improvisus (= Amphibalanus improvisus), is one of the most successful aquatic invaders worldwide, and is characterised by broad environmental tolerance. Although the species can spread through natural larval dispersal, human-mediated transport through (primarily) shipping has almost certainly contributed to the current global distribution of this species. Despite its worldwide distribution, little is known about the phylogeography of this species. Here, we characterize the population genetic structure and model dispersal dynamics of the barnacle B. improvisus, and describe how human-mediated spreading via shipping as well as natural larval dispersal may have contributed to observed genetic variation. We used both mitochondrial DNA (cytochrome c oxidase subunit I: COI) and nuclear microsatellites to characterize the genetic structure in 14 populations of B. improvisus on a global and regional scale (Baltic Sea). Genetic diversity was high in most populations, and many haplotypes were shared among populations on a global scale, indicating that long-distance dispersal (presumably through shipping and other anthropogenic activities) has played an important role in shaping the population genetic structure of this cosmopolitan species. We could not clearly confirm prior claims that B. improvisus originates from the western margins of the Atlantic coasts; although there were indications that Argentina could be part of a native region. In addition to dispersal via shipping, we show that natural larval dispersal may play an important role for further colonisation following initial introduction. PMID- 26821163 TI - Synovial Cytokines and the MSIS Criteria Are Not Useful for Determining Infection Resolution After Periprosthetic Joint Infection Explantation. AB - BACKGROUND: Diagnosing periprosthetic joint infection (PJI) requires a combination of clinical and laboratory parameters, which may be expensive and difficult to interpret. Synovial fluid cytokines have been shown to accurately differentiate septic from aseptic failed total knee (TKA) and hip (THA) arthroplasties. However, after first-stage explantation, there is still no reliable test to rule out PJI before a second-stage reimplantation procedure. QUESTIONS/PURPOSES: (1) Which synovial fluid cytokines have the highest diagnostic accuracy for PJI? (2) Which cytokine shows the greatest decrease associated with the resolution of infection in the same patient between explantation and subsequent reimplantation of an infected arthroplasty? (3) What is the accuracy of synovial fluid cytokines and the Musculoskeletal Infection Society (MSIS) criteria to rule out PJI after first-stage explantation? (4) What are the most studied synovial fluid cytokines for diagnosing PJI as reported in the literature and what are their cumulative diagnostic accuracy? METHODS: Between May 2013 and March 2014, 104 patients with painful THA and TKA evaluated for possible PJI were included in our study. Of these, 90 (87%) had cytokine levels measured from synovial fluid samples collected as part of this prospective study (n = 33 hips, n = 57 knees). A second group of 35 patients (n = 36 samples) who presented during the same time period with an antibiotic spacer also had synovial cytokines measured before second-stage reimplantation. For the first group of 90 patients, the MSIS definition classified each joint at the time of surgery as infected (n = 31) or not infected (n = 59) and was used as the standard to test the accuracy in diagnosing PJI. Of the 35 patients with synovial marker data before second-stage surgery, 15 patients had cytokine measurements both at explantation and reimplantation and were used to quantify the change between stages. The reimplantation group had a minimum 1-year followup (with four [11%] patients lost to followup) and was classified into successful or failed treatment based on Delphi-based consensus data and was used to test the accuracy in detecting infection resolution at reimplantation. RESULTS: Interleukin (IL) 1beta and interferon-gamma demonstrated the highest diagnostic utility (area under the curve 0.92, 0.91, respectively); IL-1beta and IL-6 had the highest sensitivities (0.90 [95% confidence interval {CI}, 0.74-0.98] and 0.81 [0.63 0.93]). As a measure of infection resolution, IL-1beta had the greatest decrease (12.4-fold; level at explantation: 232.4 [range, 23.1-1545.7]; level at reimplantation: 18.8 (range 1.2-298.9); mean difference: 325.5 [95% CI, 65.0 596.0]; p = 0.0001), and IL-6 had a nearly similar decrease (11.2-fold; level at explantation: 228.1 [range, 10,158.4-182,725.0]; level at reimplantation: 2518.2 [range, 10.4-41,319.3]; mean difference: 33,176.0 [95% CI, 7543.6-58,808.3]; p < 0.0001). Cytokines and MSIS criteria had low sensitivity to rule out infection in a joint treated for PJI. CONCLUSIONS: IL-6 and IL-1beta demonstrated high sensitivities to diagnose PJI and showed the greatest decrease between first and second stages, which may potentially be used to monitor treatment response to PJI. However, cytokines and MSIS criteria had low sensitivity to rule out infection before reimplantation. LEVEL OF EVIDENCE: Level III, diagnostic study. PMID- 26821164 TI - Glucocorticoid Receptor (NR3C1) Variants Associate with the Muscle Strength and Size Response to Resistance Training. AB - Glucocorticoid receptor (NR3C1) polymorphisms associate with obesity, muscle strength, and cortisol sensitivity. We examined associations among four NR3C1 polymorphisms and the muscle response to resistance training (RT). European American adults (n = 602, 23.8+/-0.4yr) completed a 12 week unilateral arm RT program. Maximum voluntary contraction (MVC) assessed isometric strength (kg) and MRI assessed biceps size (cm2) pre- and post-resistance training. Subjects were genotyped for NR3C1 -2722G>A, -1887G>A, -1017T>C, and +363A>G. Men carrying the 2722G allele gained less relative MVC (17.3+/-1.2vs33.5+/-6.1%) (p = 0.010) than AA homozygotes; men with -1887GG gained greater relative MVC than A allele carriers (19.6+/-1.4vs13.2+/-2.3%) (p = 0.016). Women carrying the -1017T allele gained greater relative size (18.7+/-0.5vs16.1+/-0.9%) (p = 0.016) than CC homozygotes. We found sex-specific NR3C1 associations with the muscle strength and size response to RT. Future studies should investigate whether these associations are partially explained by cortisol's actions in muscle tissue as they interact with sex differences in cortisol production. PMID- 26821167 TI - [User friendliness of computer-based cognitive training for psychogeriatric patients with mild to moderate cognitive impairments]. AB - Cognitive impairment associated with dementia is characterized by a continuous decline. Cognitive training is a method to train specific brain functions such as memory and attention to prevent or slow down cognitive decline. A small number of studies has shown that cognitive training on a computer has a positive effect on both cognition and mood in people with cognitive impairment. This pilot study tested if serious games could be integrated in a psychogeriatric rehabilitation center. Fourteen psychogeriatric patients participated twice weekly in cognitive training sessions on a computer. Both the participants and the facilitator reported positive interactions and outcomes. However, after five weeks only half of the sample still participated in the training. This was partly because of patient turn-over as well as incorporating this new task in the facilitators' daily work. Fear of failure, physical limitations and rapidly decreasing cognitive function led to drop out according to the facilitator. The engagement of patients in the games and the role of the facilitator seemed essential for success, especially monitoring (and adjusting) the difficulty level of the program for every individual participant. PMID- 26821166 TI - Systems-Wide Prediction of Enzyme Promiscuity Reveals a New Underground Alternative Route for Pyridoxal 5'-Phosphate Production in E. coli. AB - Recent insights suggest that non-specific and/or promiscuous enzymes are common and active across life. Understanding the role of such enzymes is an important open question in biology. Here we develop a genome-wide method, PROPER, that uses a permissive PSI-BLAST approach to predict promiscuous activities of metabolic genes. Enzyme promiscuity is typically studied experimentally using multicopy suppression, in which over-expression of a promiscuous 'replacer' gene rescues lethality caused by inactivation of a 'target' gene. We use PROPER to predict multicopy suppression in Escherichia coli, achieving highly significant overlap with published cases (hypergeometric p = 4.4e-13). We then validate three novel predicted target-replacer gene pairs in new multicopy suppression experiments. We next go beyond PROPER and develop a network-based approach, GEM-PROPER, that integrates PROPER with genome-scale metabolic modeling to predict promiscuous replacements via alternative metabolic pathways. GEM-PROPER predicts a new indirect replacer (thiG) for an essential enzyme (pdxB) in production of pyridoxal 5'-phosphate (the active form of Vitamin B6), which we validate experimentally via multicopy suppression. We perform a structural analysis of thiG to determine its potential promiscuous active site, which we validate experimentally by inactivating the pertaining residues and showing a loss of replacer activity. Thus, this study is a successful example where a computational investigation leads to a network-based identification of an indirect promiscuous replacement of a key metabolic enzyme, which would have been extremely difficult to identify directly. PMID- 26821168 TI - [Feasibility of a geriatric multidisciplinary outpatient rehabilitation program lessons learned]. AB - OBJECTIVE: To describe the feasibility of a geriatric multidisciplinary outpatient rehabilitation program, developed in Vivium Naarderheem. DESIGN: A prospective pilot study using a pretest-posttest design with measurements of the level of (social) participation, health related quality of life, and caregiver strain at the start (T0) and the end (T1) of the program. Feasibility was studied by structured interviews with participants, professionals and management. RESULTS: We included 18 patients, fifteen of which were admitted after stroke. The program was highly appreciated by patients. Management and professionals thought that factors of influence on the program were transportation of patients, adequate planning and deployment of staff, and adequate financing. The program was regarded feasible. Although some patients reported a higher level of participation, the only statistically significant finding was a deterioration in self-perceived health. CONCLUSION: In this study most of the patients participated after stroke. The geriatric multidisciplinary outpatient rehabilitation program, following inpatient geriatric rehabilitation, was highly appreciated by patients, and considered feasible by management and professionals. PMID- 26821170 TI - Gene expression under thermal stress varies across a geographical range expansion front. AB - Many ectothermic species are currently expanding their distributions polewards due to anthropogenic global warming. Molecular genetic mechanisms facilitating range expansion under these conditions are largely unknown, but understanding these could help mitigate expanding pests and disease vectors, or help explain why some species fail to track changing climates. Here, using RNA-seq data, we examine genomewide changes in gene expression under heat and cold stress in the range-expanding damselfly Ischnura elegans in northern Europe. We find that both the number of genes involved and levels of gene expression under heat stress have become attenuated during the expansion, consistent with a previously reported release from selection on heat tolerances as species move polewards. Genes upregulated under cold stress differed between core and edge populations, corroborating previously reported rapid adaptation to cooler climates at the expansion front. Expression of sixty-nine genes exhibited a region x treatment effect; these were primarily upregulated in response to heat stress in core populations but in response to cold stress at the range edge, suggesting that some cellular responses originally adapted to heat stress may switch to cold stress functionality upon encountering novel thermal selection regimes during range expansion. Transcriptional responses to thermal stress involving heat-shock and neural function genes were largely geographically conserved, while retrotransposon, regulatory, muscle function and defence gene expression patterns were more variable. Flexible mechanisms of cold-stress response and the ability of some genes to shift their function between heat and cold stress might be key mechanisms facilitating rapid poleward expansion in insects. PMID- 26821171 TI - The effect of learner's control of self-observation strategies on learning of front crawl. AB - This study investigated the effect of learner's control of self-observation strategies on motor skill learning. For this purpose, beginner and intermediate learner swimmers practised the front crawl. Seventy college students took part in this experiment. They comprised 40 novice learners, both male (n=19) and female (n=21), with an average age of 20.7 years (+/-0.44), and 30 intermediate learners, both male (n=17) and female (n=13), with an average age of 21.1 years (+/-0.86). The design involved a pretest (one day), four acquisition sessions (four days), and a retention test (one day). They were divided into three groups: (1) choice, which could choose to watch a video with their best or overall performance during practise; (2) yoked, which were paired to those of the choice group; and (3) control (did not watch any video). The measures included the performance of front crawl and self-efficacy. The results showed that: (1) beginners who chose a type of observation strategy had superior motor skill learning; (2) for intermediate learners, self-observation promoted better motor learning, regardless of the control of choices; (3) self-observation improved self-efficacy beliefs. PMID- 26821169 TI - Altered posterior cingulate brain metabolites and cognitive dysfunction in preterm adolescents. AB - BACKGROUND: Extremely preterm (EP, <28 wk gestation) individuals have increased the risk of cognitive deficits compared with controls. The posterior cingulate region has an important role in cognitive function, but how this is affected by preterm birth is unknown. We aimed to compare brain metabolite ratios of neurons and cell membranes between EP 18-y olds and controls, and explore the association between metabolite ratios and cognitive outcomes. METHOD: A regional cohort of 150 EP and 134 controls were recruited for the study. Cerebral metabolites were measured using proton magnetic resonance spectroscopy (MRS) obtained from a left posterior cingulate voxel. Total N-acetylaspartate (tNAA, neuronal marker)/total creatine (tCr), and total choline (tCho, cell membrane marker)/tCr ratios were compared between groups using linear regression. Metabolite ratios were correlated with tests of general intelligence (IQ), memory, and attention using linear or logistic regression. RESULTS: Compared with controls, EP had lower tNAA/tCr (mean difference (95% CI) of -2.27% (-4.09, -0.45)) and tCho/tCr (mean difference (95% CI) of -11.11% (-20.37, -1.85)), all P = 0.02. Higher tCho/tCr correlated with better IQ in the EP group only; whereas higher tNAA/tCr ratios correlated with better scores in working memory and attention in both groups. CONCLUSION: EP birth is associated with long-term brain metabolite ratio alterations. This may underlie poorer cognitive performance in EP survivors. PMID- 26821172 TI - Identification of a Small Benzamide Inhibitor of Influenza Virus Using a Cell Based Screening. AB - BACKGROUND: The zoonotic transmission of highly pathogenic avian influenza viruses and the global pandemic of H1N1 influenza in 2009 signified the need for a wider coverage of therapeutic options for the control of influenza. METHODS: An in-house compound library was screened using a cytopathic effect inhibition assay. Selected hits were then tested in vivo and used as a core skeleton for derivative synthesis. RESULTS: The hit compound (BMD-2601505) was effective [50% effective concentration (EC50) of 60-70 MUM] in reducing the death rate of cells infected with human influenza A and B viruses as well as avian influenza A virus. Furthermore, BMD-2601505 reduced the weight loss and increased the survival after lethal infection. The compound was further modified to enhance its antiviral potency. Results show that one derivative with bromobenzene moiety was most effective (EC50 of 22-37 MUM) against the influenza viruses tested. CONCLUSION: We identified a small benzamide compound exhibiting antiviral activity against influenza viruses. The results warrant further evaluation of antiviral activities against drug-resistant influenza isolates. PMID- 26821173 TI - Multifunctional Hydrogel Microparticles by Polymer-Assisted Photolithography. AB - Although standard lithography has been the most common technique in micropatterning, ironically it has not been adopted to produce multifunctional hydrogel microparticles, which are highly useful for bioassays. We address this issue by developing a negative photoresist-like polymer system, which is basically comprised of polyethylene glycol (PEG) triacrylate as cross-linking units and long-chain polyvinylpyrrolidone (PVP) as the supporting scaffold. We leverage standard lithography to manufacture multilayer microparticles that are intrinsically hydrophilic, low-autofluorescent, and chemically reactive. The versatility of the microparticles is demonstrated to be color-encoded, pore controllable, bioactive, and potentially used as a DNA bioassay. PMID- 26821174 TI - [Erratum to: Interdisciplinary consensus statement on airway management with supraglottic airway devices in pediatric emergency medicine--Laryngeal mask is state of the art]. PMID- 26821175 TI - [Perioperative management : New anesthesiological challenges for elderly patients]. PMID- 26821176 TI - Relationship between liver tissue stiffness and histopathological findings analyzed by shear wave elastography and compression testing in rats with non alcoholic steatohepatitis. AB - PURPOSE: The aim of the present study was to investigate two methods of determining liver stiffness in rats with various degrees of non-alcoholic steatohepatitis induced by a methionine- and choline-deficient (MCD) diet by comparing each finding with reference to histopathological liver findings. METHODS: Twenty male Wister rats were fed an MCD diet for up to 32 weeks, and four were fed a normal diet. Ultrasound-based shear wave elastography (SWE) and mechanical compression testing using an Instron Universal Testing machine were performed on each rat at designated time points. After each examination, liver histopathology was analyzed to evaluate the degrees of steatosis, inflammation, and fibrosis based on non-alcoholic fatty liver disease (NAFLD) activity score, and each finding was compared with reference to liver histopathologic findings. RESULTS: Median liver stiffness values measured using SWE showed a stepwise increase with increasing histological inflammation score (P = 0.002), hepatic fibrosis stage (P = 0.029), ballooning score (P = 0.012), and steatosis grade (P = 0.030). Median liver stiffness measured using an Instron machine showed a stepwise increase only with increasing histological fibrosis stage (P = 0.033). CONCLUSIONS: Degree of liver stiffness measured by SWE and the Instron machine differed. SWE reflected mainly inflammation, whereas Instron machine-derived values primarily reflected fibrosis. This is the main source of discrepancies between measurements made with these two modalities. PMID- 26821177 TI - A novel virulence-associated protein, vapE, in Streptococcus suis serotype 2. AB - Streptococcus suis serotype 2 (SS2) is an important pathogen that affects pigs. However, neither its virulence nor its pathogenesis of infection has yet to be fully elucidated. The present study identifies a novel virulence-associated protein E gene (vapE) of SS2. To investigate the importance of vapE in SS2 infection, a vapE knock-out mutant based on SS2 wild-type strain ZY458 was designated 458DeltavapE. 458DeltavapE was generated through homologous recombination, using a combined plasmid with a vapE knock-out fragment and a pSET4s suicide vector. Additionally, the 458DeltavapE strain was transformed by a pAT18 shuttle plasmid containing the vapE gene. A functionally complemented strain for the vapE gene [termed 458DeltavapE (pvapE)] was constructed. Animal experiments demonstrated that mice infected with ZY458 and 458DeltavapE (pvapE) exhibited severe clinical symptoms, including depression, apathy, fever, anorexia, emaciation, swollen eyes and neural disorders, and died within two days of infection. All mice infected with ZY458, and 85% of mice infected with 458DeltavapE (pvapE), died within 2 days of infection. In contrast, mice inoculated with 458DeltavapE exhibited only mild clinical symptoms in the first 2 days following infection, and recovered within a week. A bacterial colonization assay demonstrated the ability of the 458DeltavapE mutant SS2 strain to colonize the heart, liver, spleen, lung and kidney of infected mice. PCR analysis of the vapE gene revealed that functional vapE was detected in virulent strains, but not in avirulent and carrier strains of S. suis SS2. These findings indicate that vapE is important for the pathogenesis of SS2. PMID- 26821178 TI - Long Noncoding RNA MALAT-1 Can Predict Poor Prognosis: A Meta-Analysis. AB - BACKGROUND: MALAT-1 is a highly conserved nuclear long non-coding RNA (lncRNA). The overexpression of MALAT-1 has been reported in several types of cancers. This meta-analysis was conducted to further investigate its potential role as a prognostic indicator in various cancers. MATERIAL/METHODS: The meta-analysis was performed by use of systematic search terms in 13 databases for qualified papers on prognosis in cancer from inception to June 30, 2015. The combined hazard ratios (HRs) with 95% confidence interval (95% CI) were computed to demonstrate the effect of MALAT-1 on prognosis of cancers. RESULTS: A total of 590 papers were initially identified, and 17 studies were finally included in this paper. Meta-analysis was accomplished with a total of 1626 patients. Combined HRs and 95% CI were calculated by fixed-effects or random-effects models. The quality assessment of included studies was performed by the Newcastle-Ottawa scale (NOS). High expression of MALAT-1 was found to be an indicator of poor prognosis in overall survival (OS) (HR=1.84, 95% CI: 1.27-2.67) and disease-free survival (DFS) (HR=2.37, 95% CI: 1.55-3.62). In subgroups, the associations between MALAT 1 and survival were also apparent, for instance, in country subgroup: China (HR=1.85, 95% CI: 1.14-2.99). CONCLUSIONS: The overexpression of MALAT-1 may be a potential prognostic indicator for various human cancers. PMID- 26821180 TI - Vulnerable Patients and Potential Harms: The Contribution of Observational Research. PMID- 26821179 TI - Acute Uncomplicated Febrile Illness in Children Aged 2-59 months in Zanzibar - Aetiologies, Antibiotic Treatment and Outcome. AB - BACKGROUND: Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission. METHODS: We prospectively studied the aetiology of febrile illness in 677 children aged 2-59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q)PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated. FINDINGS: NPH-qPCR and GE-qPCR detected >=1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection retrospectively considered to require antibiotics. Clinical outcome was generally good. However, two children died. Only 68 (11%) patients remained febrile on day 3 and three of them had verified fever on day 14. An additional 29 (4.5%) children had fever relapse on day 14. Regression analysis determined C-reactive Protein (CRP) as the only independent variable significantly associated with CXR-confirmed pneumonia. CONCLUSIONS: This is the first study on uncomplicated febrile illness in African children that both applied a comprehensive laboratory panel and a healthy control group. A majority of patients had viral respiratory tract infection. Pathogens were frequently detected by qPCR also in asymptomatic children, demonstrating the importance of incorporating controls in fever aetiology studies. The precision of IMCI for identifying infections requiring antibiotics was low. PMID- 26821183 TI - Zirconium(IV) Phosphonate-Phosphates as Efficient Ion-Exchange Materials. AB - Layered metal phosphonate-phosphate hybrid materials are known to be ion-exchange materials. Hybrids with zirconium metal centers were synthesized at varying phosphonate-phosphate ratios in order to explore the function and charge preference. The zirconium hybrid materials were found to have a range of applicable uses with preference for highly charged ions (3+) over lower charged ions (1+ and 2+). The addition of a large excess of phosphate altered the selectivity, and these materials were able to remove all ions from solution regardless of charge. In this paper, we describe newly synthesized compounds that are simple to prepare, reproducible, stable, and offer a variety of separation schemes. PMID- 26821181 TI - Differences by gender at twelve months in a brief intervention trial among Mexican-origin young adults in the emergency department. AB - In this study, we investigate the role of gender in prevalence and consequences of binge drinking and brief intervention outcomes among Mexican-origin young adults aged 18-30 years at the U.S.-Mexico border. We conducted a secondary analysis, stratified by gender, from a randomized controlled trial of a brief motivational intervention in a hospital emergency department. Intervention effects for males included reductions in drinking frequency, binge drinking, and alcohol-related consequences. For females the intervention was associated with reduction in drinking frequency and binge drinking but did not have a significant effect on alcohol-related consequences. Results suggest a new direction for tailoring interventions to gender. PMID- 26821182 TI - RNASeq Based Transcriptional Profiling of Pseudomonas aeruginosa PA14 after Short and Long-Term Anoxic Cultivation in Synthetic Cystic Fibrosis Sputum Medium. AB - The opportunistic human pathogen Pseudomonas aeruginosa can thrive under microaerophilic to anaerobic conditions in the lungs of cystic fibrosis patients. RNASeq based comparative RNA profiling of the clinical isolate PA14 cultured in synthetic cystic fibrosis medium was performed after planktonic growth (OD600 = 2.0; P), 30 min after shift to anaerobiosis (A-30) and after anaerobic biofilm growth for 96h (B-96) with the aim to reveal differentially regulated functions impacting on sustained anoxic biofilm formation as well as on tolerance towards different antibiotics. Most notably, functions involved in sulfur metabolism were found to be up-regulated in B-96 cells when compared to A-30 cells. Based on the transcriptome studies a set of transposon mutants were screened, which revealed novel functions involved in anoxic biofilm growth.In addition, these studies revealed a decreased and an increased abundance of the oprD and the mexCD-oprJ operon transcripts, respectively, in B-96 cells, which may explain their increased tolerance towards meropenem and to antibiotics that are expelled by the MexCD-OprD efflux pump. The OprI protein has been implicated as a target for cationic antimicrobial peptides, such as SMAP-29. The transcriptome and subsequent Northern-blot analyses showed that the abundance of the oprI transcript encoding the OprI protein is strongly decreased in B-96 cells. However, follow up studies revealed that the susceptibility of a constructed PA14DeltaoprI mutant towards SMAP-29 was indistinguishable from the parental wild type strain, which questions OprI as a target for this antimicrobial peptide in strain PA14. PMID- 26821184 TI - The smell of "anxiety": Behavioral modulation by experimental anosmia in zebrafish. AB - Olfaction is strongly involved in the regulation of fish behavior, including reproductive, defensive, social and migration behaviors. In fish, anosmia (the lack of olfaction) can be induced experimentally, impairing their ability to respond to various olfactory stimuli. Here, we examine the effects of experimental lidocaine-induced anosmia on anxiety-like behavior and whole-body cortisol levels in adult zebrafish (Danio rerio). We show that experimentally induced anosmia reduces anxiolytic-like behavioral effects of fluoxetine and seems to interact with anxiogenic effect of stress also paralleling cortisol responses in zebrafish. These findings provide first experimental evidence that temporary anosmia modulates anxiety-like behaviors and physiology in adult zebrafish. PMID- 26821185 TI - Free-living cross-comparison of two wearable monitors for sleep and physical activity in healthy young adults. AB - There is a growing need for free-living monitoring of the full 24 h spectrum of behaviors with a single or integrated set of sensors. The validity of field standard wearable monitors in sleep and physical activity have yet to be assessed for the complementary behavior in the context of 24 h continuous monitoring. We conducted a free-living comparison study of the Actigraph GT3X+ (GT3X+) to assess sleep parameters as compared with the Actiwatch-64 (AW-64) and concurrently, the AW-64 to assess sedentary and physical activity behaviors as compared with the GT3X+. Thirty young adults (15 female, 19.2+/-0.86 years) wore both monitors for 3 consecutive days and 2 consecutive nights. Agreement of sleep, sedentary, and physical activity metrics were evaluated using analyses of variance, intraclass correlation coefficients, Bland-Altman plots with associated confidence limits, mean absolute percentage of errors and equivalence tests. For sleep, the GT3X+ showed high agreement for total sleep time and sleep efficiency, but underestimated wakefulness after sleep onset and sleep onset latency relative to the AW-64. For sedentary behavior and physical activity, the AW-64 showed a moderate agreement for activity energy expenditure, but not for sedentary, light or moderate-vigorous physical activities relative to the GT3X+. Overall our results showed good agreement of the GT3X+ with AW-64 for assessing sleep but a lack of agreement between AW-64 and GT3X+ for physical activity and sedentary behaviors. These results are likely due to the monitor placement (wrist vs hip), as well as the algorithm employed to score the data. Future validation work of existing and emerging technologies that may hold promise for 24 h continuous monitoring is needed. PMID- 26821186 TI - Cognitive-enhancing activities of the polyprenol preparation Ropren(r) in gonadectomized beta-amyloid (25-35) rat model of Alzheimer's disease. AB - The present preclinical study was designed to examine the effects of prolonged Ropren(r) administration (8.6 mg/kg, orally, once daily, 28 days) in a beta amyloid (25-35) rat model of Alzheimer's disease following gonadectomy. The experimental model was created by intracerebroventricular injection of beta amyloid (25-35) into gonadectomized (GDX) rats and GDX rats with testosterone propionate (TP, 0.5mg/kg, subcutaneous, once daily, 28 days) supplementation. Ropren(r) was administered to the GDX rats and GDX rats treated with TP. Memory performance was assessed using the passive avoidance and the Morris water maze tests and the spontaneous locomotor activity was assessed using the open field test. Treatment with Ropren(r) significantly improved and restored the cognitive ability of GDX rats with beta-amyloid (25-35)-induced amnesia in the passive avoidance test and Morris water maze. Co-administration of Ropren(r) with TP exerted a markedly synergistic memory-enhancing effect in the GDX rats with beta amyloid (25-35)-induced amnesia on the same models of memory testing. Ropren(r) administered alone or together with TP significantly enhanced crossing, frequency of rearing and grooming of the GDX rats with beta-amyloid (25-35)-induced amnesia in the open field test. These results indicate that Ropren(r) has a marked memory enhancing action in the experimental model of Alzheimer's disease in male rats with altered levels of androgens. PMID- 26821187 TI - Visual acuity in an opportunistic raptor, the chimango caracara (Milvago chimango). AB - Raptors are always considered to have an extraordinary resolving power of their eyes (high visual acuity). Nevertheless, raptors differ in their diet and foraging tactics, which could lead to large differences in visual acuity. The visual acuity of an opportunist bird of prey, the Chimango caracara (Mivalgo chimango) was estimated by operant conditioning. Three birds were trained to discriminate two stimuli, a positive grey uniform pattern and a negative grating pattern stimulus. The visual acuity range from 15.08 to 39.83 cycles/degrees. When compared to other birds, they have a higher visual acuity than non-raptorial birds, but they have the lowest visual acuity found in bird of prey so far. We discuss this result in the context of the ecology of the bird, with special focus on it is foraging tactic. PMID- 26821188 TI - The role of trigeminal nucleus caudalis orexin 1 receptors in orofacial pain transmission and in orofacial pain-induced learning and memory impairment in rats. AB - It is widely accepted that the spinal trigeminal nuclear complex, especially the subnucleus caudalis (Vc), receives input from orofacial structures. The neuropeptides orexin-A and -B are expressed in multiple neuronal systems. Orexin signaling has been implicated in pain-modulating system as well as learning and memory processes. Orexin 1 receptor (OX1R) has been reported in trigeminal nucleus caudalis. However, its roles in trigeminal pain modulation have not been elucidated so far. This study was designed to investigate the role of Vc OX1R in the modulation of orofacial pain as well as pain-induced learning and memory deficits. Orofacial pain was induced by subcutaneous injection of capsaicin in the right upper lip of the rats. OX1R agonist (orexin-A) and antagonist (SB 334867-A) were microinjected into Vc prior capsaicin administration. After recording nociceptive times, learning and memory was investigated using Morris water maze (MWM) test. The results indicated that, orexin-A (150 pM/rat) significantly reduced the nociceptive times, while SB334867-A (80 nM/rat) exaggerated nociceptive behavior in response to capsaicin injection. In MWM test, capsaicin-treated rats showed a significant learning and memory impairment. Moreover, SB-334867-A (80 nM/rat) significantly exaggerated learning and memory impairment in capsaicin-treated rats. However, administration of orexin-A (100 pM/rat) prevented learning and memory deficits. Taken together, these results indicate that Vc OX1R was at least in part involved in orofacial pain transmission and orexin-A has also a beneficial inhibitory effect on orofacial pain-induced deficits in abilities of spatial learning and memory. PMID- 26821189 TI - Prospective, randomized, double-blinded, double-dummy and multicenter phase IV clinical study comparing the efficacy and safety of PG201 (Layla) and SKI306X in patients with osteoarthritis. AB - ETHNOPHARMACOLOGICAL RELEVANCE: This prospective, randomized, double-blinded, double-dummy, multicenter study compared the efficacy and safety of PG201 (Layla(r)), a new product from extracts of 12 plant sources and SKI306X (Joins(r)) which have been well investigated and in relatively wide usage among herbal medicine, for the treatment of patients with knee osteoarthritis. AIM OF THE STUDY: To compare the efficacy and safety of PG201 and SKI306X in patients with knee osteoarthritis. MATERIALS AND METHODS: A prospective, double-blinded multicenter study was conducted in 124 patients with Kellgren and Lawrence grade 2-3 knee osteoarthritis. Patients were randomly assigned to receive 600mg of PG201 (300mg, twice daily) and 600mg of SKI306X placebo (200mg, thrice daily) or 600mg of SKI306X (200mg, thrice daily) and PG201 placebo (300mg, twice daily) for 12 weeks. The primary outcome was the improvement of pain by week 8 as assessed by the 100-mm pain visual analog scale (VAS). Secondary outcomes included pain VAS improvement level at week 12, pain VAS improvement rate at weeks 8 and 12, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) improvement level at weeks 8 and 12, the improvement of the quality of life (EQ 5D), overall symptom self-assessment score, and rescue medication consumption. RESULTS: The pain VAS improvement at 8 weeks was 14.2+/-16.2 in the experimental group and 11.9+/-13.1 in control group (p=0.557), confirming that the experimental group was not inferior to the control group as lower limit (-8.38) of 95% CI of the difference of VAS improvement between two groups was well above the allowed limit (-10 mm). There was no significant difference in all secondary outcomes including pain VAS, WOMAC, EQ-5D, overall symptom self-assessment score, and rescue medication consumption. Adverse events were low and similar between the two groups. CONCLUSIONS: The results of this study showed that PG201 significantly reduced knee pain and improved knee function and were comparable to SKI306X. PG201 can be suggested as an effective treatment of knee osteoarthritis. Trial registration ClinicalTrials.gov:NCT01768468. PMID- 26821190 TI - Traditional uses, phytochemistry and pharmacological properties of Neolamarckia cadamba: A review. AB - ETHNOPHARMACOLOGICAL RELEVANCE: There are more than 3000 officially documented plants in the Indian subcontinent that hold great medicinal potential. One such under-explored plant is an evergreen tropical tree Neolamarckia cadamba (Roxb.) Bosser (Rubiaceae). It is widely distributed in tropical and subtropical regions of the world and has therapeutic potential against many diseases such as diabetes, anaemia, stomatitis, leprosy, cancer and infectious diseases. Neolamarckia cadamba has historical existence in India and it is mentioned in mythical stories. There are several reports on medicinal values of root, bark and leaves of N. cadamba; but the literature on its fruits is scanty. Therefore, the present review aims to provide updated comprehensive information on the phytochemistry and pharmacological properties of different parts of N. cadamba tree with special reference to its fruit, in order to open new perspectives for future food and pharmacological research. MATERIALS AND METHODS: A literature search was performed on N. cadamba using ethnobotanical textbooks, published articles in peer-reviewed journals, unpublished materials, government survey reports and scientific databases such as Pubmed, Scopus, Web of Science, Science Direct, Google Scholar and other web search engines (Google, Yahoo). The Plant List, International Plant Name Index and Kew Botanical Garden Plant name databases were used to validate the scientific names. RESULTS AND DISCUSSION: Neolamarckia cadamba is one of the economically important trees, which is being exploited for paper, pulp and wood industry. In folk medicine, various parts of N. cadamba are used in the treatment of various ailments such as fever, uterine complaints, blood diseases, skin diseases, tumour, anaemia, eye inflammation and diarrhoea. Other reported uses of N. cadamba include antihepatotoxic, antimalarial, analgesic, anti-inflammatory, antipyretic, diuretic and laxative. Various phytochemicals such as cadambine and its derivatives (dihydrocadambine and isodihydrocadambine) and indole alkaloids (Neolamarckines) were isolated from the leaves; whereas the presence of quinovic acid derivatives have been reported in the bark of N. cadamba. CONCLUSION: The present review compiles information on an ethnopharmacologically useful plant N. cadamba. Bioactive compounds responsible for its various medicinal properties and their effects at the molecular level need to be investigated in more detail. Furthermore, the detailed study of toxicity and pharmacological properties of extracts as well as molecules in N. cadamba is required to confirm the ethnomedicinal claims of N. cadamba for food and pharmaceutical applications. PMID- 26821192 TI - Microsolvated F(-)(H2O) + CH3I S(N)2 Reaction Dynamics. Insight into the Suppressed Formation of Solvated Products. AB - Microsolvation offers a bottom-up approach to investigate details of how solute solvent interactions affect chemical reaction dynamics. The dynamics of the microsolvated S(N)2 reaction F(-)(H2O) + CH3I are uncovered in detail by using direct chemical dynamics simulations. Direct rebound and stripping and indirect atomic-level mechanisms are observed. The indirect events comprise ~70% of the solvated reaction and occur predominantly via a hydrogen-bonded F(-)(H2O)...HCH2I prereaction complex. The reaction dynamics show propensity for the direct three body dissociation channel F(-)(H2O) + CH3I -> CH3F + I(-) + H2O after passing the reaction's dynamical bottleneck. The water molecule leaves the reactive system before traversing the postreaction region of the PES, where water transfer toward the product species occurs. This provides an insight into the very interesting finding of strongly suppressed formation of energetically favored solvated products for almost all SN2 reactions under microsolvation. PMID- 26821193 TI - Perceived threat and depression among patients with cancer: the moderating role of health locus of control. AB - Illness perception was found to be a better predictor of psychological outcome among cancer patients than the objective characteristics of illness. The current study explored the association between the perceived threat of illness (a major aspect of illness perception) and depression among cancer patients. We examined the hypothesis that this association will be higher for persons with low External (others) or internal (self) Health Locus of Control (HLC) than for those with high HLC. The study took an exploratory approach regarding the role that different sources of control (external and internal) may assume. Fifty-seven cancer patients completed self-report measures of Perceived Life Threat (PLT), HLC and Depression. The possible moderating role of HLC on the relationship between PLT and Depression was examined. A significant relationship between perceived threat and depression was found only among participants reporting low levels of internal locus of control. The results support the hypothesis that perception of cancer as life threatening is important factor in determining the level of depression among cancer patients. The results also support the differentiation between internal and external HLC and suggest that internal HLC may be more relevant than external HLC in managing perceived threat. Internal locus of control can be interpreted as having a sense of agency and mastery which is important in managing the cognitive perception of the threat of illness. Further research is needed in order to determine the role of external HLC in managing perceived or actual threats. PMID- 26821191 TI - Src promotes cutaneous wound healing by regulating MMP-2 through the ERK pathway. AB - Wound healing is a highly orchestrated, multistep process, and delayed wound healing is a significant symptomatic clinical problem. Keratinocyte migration and re-epithelialization play the most important roles in wound healing, as they determine the rate of wound healing. In our previous study, we found that Src, one of the oldest proto-oncogenes encoding a membrane-associated, non-receptor protein tyrosine kinase, promotes keratinocyte migration. We therefore hypothesized that Src promotes wound healing through enhanced keratinocyte migration. In order to test this hypothesis, vectors for overexpressing Src and small interfering RNAs (siRNAs) for silencing of Src were used in the present study. We found that the overexpression of Src accelerated keratinocyte migration in vitro and promoted wound healing in vivo without exerting a marked effect on cell proliferation. The extracellular signal-regulated kinase (ERK) and c-Jun N terminal kinase (JNK) signaling pathways play important roles in Src-accelerated keratinocyte migration. Further experiments demonstrated that Src induced the protein expression of matrix metalloproteinase-2 (MMP-2) and decreased the protein expression of E-cadherin. We suggest that ERK signaling is involved in the Src-mediated regulation of MMP-2 expression. The present study provided evidence that Src promotes keratinocyte migration and cutaneous wound healing, in which the regulation of MMP-2 through the ERK pathway plays an important role, and thus we also demonstrated a potential therapeutic role for Src in cutaneous wound healing. PMID- 26821194 TI - Prior Misdiagnosis of Celiac Disease Is Common Among Patients Referred to a Tertiary Care Center: A Prospective Cohort Study. AB - OBJECTIVES: Interest of patients and physicians in celiac disease is growing worldwide, but without a corresponding increase in the awareness of the disease. Many patients are diagnosed as celiacs even without completing the whole diagnostic process, with consequent risk of misdiagnosis and delay in the evaluation of other diseases. The objective of this study was to assess the rates of prior celiac disease misdiagnosis among patients referred to a tertiary care center. METHODS: From June 2013 to December 2014, we prospectively recruited patients referred for the first time to our Celiac Disease Center. Patients with a previous diagnosis of celiac disease underwent a diagnostic revaluation by second reading of duodenal tissue slides, dosage of specific antibodies, and/or duodenal biopsy sampling; HLA status was investigated in pertinent cases. RESULTS: A total of 198 subjects were recruited. Of these, 91 "naive" patients (46%) started the diagnostic screening for celiac disease; 58 of them (64-29% of the whole sample) were diagnosed as celiacs. The remaining 107 patients (54%) came with a previous diagnosis of celiac disease: of these, 52 (49-26% of the whole sample) presented with confirmed diagnosis of celiac disease, whereas 55 (51-28% of the whole sample) underwent diagnostic revaluation. After the reassessment, diagnosis was rejected in 43 cases (78-22% of the whole sample) and confirmed in the remaining 12 (22-6% of the whole sample). Overall, diagnosis was confirmed in only 64 of the 107 subjects with a previous diagnosis (60-32% of the whole sample). Diagnosis of celiac disease was more frequently confirmed in "naive" patients compared those with a questionable previous diagnosis (64% vs. 22%; P<0.0001). CONCLUSIONS: A considerable number of patients referred to a tertiary care center are inaccurately diagnosed with celiac disease. Although we cannot exclude that uncertain diagnosis was a reason for the referral, we suggest greater adherence to guidelines to minimize the burden of celiac disease misdiagnosis. PMID- 26821195 TI - Genetic Associations of Obesity: The Fat-Mass and Obesity-Associated (FTO) Gene. PMID- 26821196 TI - Use of Macrophage Inhibitory Cytokine-1 as a Biomarker in Screening and Surveillance of Colorectal Neoplasia. PMID- 26821197 TI - Examining potential iatrogenic effects of viewing suicide and self-injury stimuli. AB - The high-stakes nature of self-injurious thoughts and behaviors (SITBs) raises ethical questions and concerns. The authors examined the iatrogenic risk of recently developed behavioral measures such as the suicide or self-injury Implicit Association Tests (IATs), which include repeated and rapid presentation of SITB-related images (e.g., of cut skin) and words (e.g., death, suicide). The impact of these IATs was investigated across a series of 3 studies involving: adult web-based respondents (n = 3,304), undergraduate students (n = 100), and adolescent psychiatric inpatients (n = 89). There was minimal change in self injurious or suicidal urges detected across all IAT studies. A slight mood decline was detected across the 3 samples, but was isolated to female research participants and 1 type of IAT that presented SITB-related images (vs. words only). Given the increasing use of novel SITB-relevant stimuli in behavioral and neurobiological studies, these findings may help researchers balance clinical sensitivity and clinical science. (PsycINFO Database Record PMID- 26821198 TI - Measuring depression over time . . . Or not? Lack of unidimensionality and longitudinal measurement invariance in four common rating scales of depression. AB - In depression research, symptoms are routinely assessed via rating scales and added to construct sum-scores. These scores are used as a proxy for depression severity in cross-sectional research, and differences in sum-scores over time are taken to reflect changes in an underlying depression construct. To allow for such interpretations, rating scales must (a) measure a single construct, and (b) measure that construct in the same way across time. These requirements are referred to as unidimensionality and measurement invariance. We investigated these 2 requirements in 2 large prospective studies (combined n = 3,509) in which overall depression levels decrease, examining 4 common depression rating scales (1 self-report, 3 clinician-report) with different time intervals between assessments (between 6 weeks and 2 years). A consistent pattern of results emerged. For all instruments, neither unidimensionality nor measurement invariance appeared remotely tenable. At least 3 factors were required to describe each scale, and the factor structure changed over time. Typically, the structure became less multifactorial as depression severity decreased (without however reaching unidimensionality). The decrease in the sum-scores was accompanied by an increase in the variances of the sum-scores, and increases in internal consistency. These findings challenge the common interpretation of sum scores and their changes as reflecting 1 underlying construct. The violations of common measurement requirements are sufficiently severe to suggest alternative interpretations of depression sum-scores as formative instead of reflective measures. We discuss the possible causes of these violations such as response shift bias, restriction of range, and regression to the mean. (PsycINFO Database Record PMID- 26821199 TI - Development and validation of the Family Law DOORS. AB - When former spouses experience distress and dispute following separation, risks to well-being and to safety are heightened for all family members. Reliable family-wide risk screening is essential. The Family Law DOORS (Detection of Overall Risk Screen) is a 3-part screening framework to assist identification, evaluation, and response to safety and well-being risks in separated families. Uniquely, the Family Law DOORS screens for victimization and perpetration risks and appraises infant and child developmental risk. The Family Law DOORS self report screening tool is the subject of this report. Internal scale reliability and concurrent and external criterion validity for the Family Law DOORS were estimated with a community sample of 660 separated parents, including 181 mother father pairs. Overall psychometric properties are strong and demonstrate good potential for the Family Law DOORS to support early risk detection for separating families. (PsycINFO Database Record PMID- 26821200 TI - N-Acetyl cysteine does not prevent liver toxicity from chronic low-dose plus subacute high-dose paracetamol exposure in young or old mice. AB - Paracetamol is an analgesic commonly used by people of all ages, which is well documented to cause severe hepatotoxicity with acute overexposures. The risk of hepatotoxicity from nonacute paracetamol exposures is less extensively studied, and this is the exposure most common in older adults. Evidence on the effectiveness of N-acetyl cysteine (NAC) for nonacute paracetamol exposures, in any age group, is lacking. This study aimed to examine the effect of long-term exposure to therapeutic doses of paracetamol and subacute paracetamol overexposure, in young and old mice, and to investigate whether NAC was effective at preventing paracetamol hepatotoxicity induced by these exposures. Young and old male C57BL/6 mice were fed a paracetamol-containing (1.33 g/kg food) or control diet for 6 weeks. Mice were then dosed orally eight times over 3 days with additional paracetamol (250 mg/kg) or saline, followed by either one or two doses of oral NAC (1200 mg/kg) or saline. Chronic low-dose paracetamol exposure did not cause hepatotoxicity in young or old mice, measured by serum alanine aminotransferase (ALT) elevation, and confirmed by histology and a DNA fragmentation assay. Subacute paracetamol exposure caused significant hepatotoxicity in young and old mice, measured by biochemistry (ALT) and histology. Neither a single nor double dose of NAC protected against this toxicity from subacute paracetamol in young or old mice. This finding has important clinical implications for treating toxicity due to different paracetamol exposure types in patients of all ages, and implies a need to develop new treatments for subacute paracetamol toxicity. PMID- 26821201 TI - The new holism: P4 systems medicine and the medicalization of health and life itself. AB - The emerging concept of systems medicine (or 'P4 medicine'-predictive, preventive, personalized and participatory) is at the vanguard of the post genomic movement towards 'precision medicine'. It is the medical application of systems biology, the biological study of wholes. Of particular interest, P4 systems medicine is currently promised as a revolutionary new biomedical approach that is holistic rather than reductionist. This article analyzes its concept of holism, both with regard to methods and conceptualization of health and disease. Rather than representing a medical holism associated with basic humanistic ideas, we find a technoscientific holism resulting from altered technological and theoretical circumstances in biology. We argue that this holism, which is aimed at disease prevention and health optimization, points towards an expanded form of medicalization, which we call 'holistic medicalization': Each person's whole life process is defined in biomedical, technoscientific terms as quantifiable and controllable and underlain a regime of medical control that is holistic in that it is all-encompassing. It is directed at all levels of functioning, from the molecular to the social, continual throughout life and aimed at managing the whole continuum from cure of disease to optimization of health. We argue that this medicalization is a very concrete materialization of a broader trend in medicine and society, which we call 'the medicalization of health and life itself'. We explicate this holistic medicalization, discuss potential harms and conclude by calling for preventive measures aimed at avoiding eventual harmful effects of overmedicalization in systems medicine (quaternary prevention). PMID- 26821202 TI - Did the crew of the submarine H.L. Hunley suffocate? AB - On the evening of February 17th, 1864, the Confederate submarine H.L. Hunley attacked the Union ship USS Housatonic outside Charleston, South Carolina and became the first submarine in history to successfully sink an enemy ship in combat. One hypothesis for the sinking of the Confederate submarine H.L. Hunley is that the crew, in the enclosed vessel, suffered a lack of oxygen and suffocated. This study estimates the effects of hypoxia and hypercapnia on the crew based on submarine gas volume and crew breathing dynamics. The calculations show the crew of the Hunley had a minimum of 10 min between the onset of uncomfortable hypercapnia symptoms and danger of loss of consciousness from hypoxia. Based on this result and the location of the crew when discovered, hypoxia and hypercapnia do not explain the sinking of the world's first successful combat submarine. PMID- 26821203 TI - Direct analysis in real time high resolution mass spectrometry as a tool for rapid characterization of mind-altering plant materials and revelation of supplement adulteration--The case of Kanna. AB - We demonstrate the utility of direct analysis in real time ionization coupled with high resolution time-of-flight mass spectrometry (DART-HRTOFMS) in revealing the adulteration of commercially available Sceletium tortuosum, a mind-altering plant-based drug commonly known as Kanna. Accurate masses consistent with alkaloids previously isolated from S. tortuosum plant material enabled identification of the products as Kanna, and in-source collision-induced dissociation (CID) confirmed the presence of one of these alkaloids, hordenine, while simultaneously revealing the presence of an adulterant. The stimulant ephedrine, which has been banned in herbal products and supplements, was confirmed to be present in a sample through the use of in-source CID. High throughput DART-HRTOFMS was shown to be a powerful tool to not only screen plant based drugs of abuse for psychotropic alkaloids, but also to reveal the presence of scheduled substances and adulterants. PMID- 26821204 TI - Seven major genomic deletions of vaccinia virus Tiantan strain are sufficient to decrease pathogenicity. AB - Attenuated strain TTVAC7, as a multi-gene-deleted vaccinia virus Tiantan strain (VTT), was constructed by knocking out parts of non-essential genes related to virulence, host range and immunomodulation of VTT, and by combining double marker screening with exogenous selectable marker knockout techniques. In this study, shuttle vector plasmids pTC-EGFP, pTA35-EGFP, pTA66-EGFP, pTE-EGFP, pTB-EGFP, pTI EGFP and pTJ-EGFP were constructed, which contained seven pairs of recombinant arms linked to the early and late strong promoter pE/L, as well as to enhanced green fluorescent protein (EGFP) as an exogenous selectable marker. BHK cells were co-transfected/infected successively with the above plasmids and VTT or gene deleted VTT, and homologous recombination and fluorescence plaque screening methods were used to knock out the gene fragments (TC: TC7L ~ TK2L; TA35: TA35L; TA66: TA66R; TE: TE3L ~ TE4L; TB: TB13R; TI: TI4L; TJ: TJ2R). The Cre/LoxP system was then applied to knock out the exogenous selectable marker, and ultimately the gene-deleted attenuated strain TTVAC7 was obtained. A series of in vivo and in vitro experiments demonstrated that not only the host range of TTVAC7 could be narrowed and its toxicity weakened significantly, but its high immunogenicity was maintained at the same time. These results support the potential of TTVAC7 to be developed as a safe viral vector or vaccine. PMID- 26821205 TI - One-prime multi-boost strategy immunization with recombinant DNA, adenovirus, and MVA vector vaccines expressing HPV16 L1 induces potent, sustained, and specific immune response in mice. AB - Human papillomavirus (HPV) is associated with various human diseases, including cancer, and developing vaccines is a cost-efficient strategy to prevent HPV related disease. The major capsid protein L1, which an increasing number of studies have confirmed is typically expressed early in infection, is a promising antigen for such a vaccine, although the E6 and E7 proteins have been characterized more extensively. Thus, the L1 gene from HPV16 was inserted into a recombinant vector, AdHu5, and MVA viral vectors, and administered by prime-boost immunization. Virus-like particles were used as control antigens. Our results indicate that prime-boost immunization with heterologous vaccines induced robust and sustained cellular and humoral response specific to HPV16 L1. In particular, sera obtained from mice immunized with DNA + DNA + Ad + MVA had excellent antitumor activity in vivo. However, the data also confirm that virus-like particles can only elicit low levels cellular immunity and not be long-lasting, and are therefore unsuitable for treatment of existing HPV infections. PMID- 26821206 TI - 3D Cell-SELEX: Development of RNA aptamers as molecular probes for PC-3 tumor cell line. AB - Human prostate cancer (PCa) is a highly heterogeneous and multifactorial disease. Current clinical biomarkers are not sufficiently accurate, thus being unable to predict the clinical outcome. Therefore, searching for new biomarkers aiming to improve diagnosis, prognosis and therapy is still required. In this study, we performed 3D Cell-SELEX against PC-3 prostate cancer cell line, a novel strategy to select specific nucleic acid ligands against spheroid cells in 3D cell culture. This original system combines Cell-SELEX, a process that exploits the cellular structure to generate specific ligands, and 3D cell culture, an approach that mimics the tissue microenvironment in vitro. In the first round of 3D Cell SELEX, a negative selection against RWPE-1, non-tumor cell line, was performed to subtract non-tumor specific aptamers. The supernatant was used in eight additional rounds of selection, which were performed against PC-3 cell line. After nine selection cycles, eight PC-3 specific RNA aptamers were selected and sequenced. The aptamers presented sizes between 20 and 50 nucleotides-long, with low free energy (?G<-13.6), which contributed for their spontaneous folding and high stability. Furthermore, our results showed the aptamer A4 as a specific ligand to prostate tumor cells, with dissociation constant in the nanomolar scale. Therefore, the novel 3D Cell-SELEX procedure improved the selection of PCa cell-surface ligands and the aptamer A4 has shown potential for the identification of prostate tumor cells, suggesting the application of this molecule in further screening assays for PCa. PMID- 26821207 TI - Evaluation of the uniformity of concentration of radon in a radon chamber. AB - In order to solve the problem that the evaluation results of the uniformity of concentration of radon in a radon chamber via various methods were difficult to compare, according to its statistical properties, a mathematical model was built to analyze the uniformity of concentration of radon; an evaluation method for the overall uniformity of concentration of radon was proposed on the basis of single factor multi-group ANOVA, and a detection method for nonuniform points in a radon chamber was proposed on the basis of single-factor two-group t-test; an evaluation process of the uniformity of concentration of radon in a radon chamber was established. The proposed method was applied to evaluate the HD-6 small and medium-sized radon chambers and achieved good results. PMID- 26821208 TI - Development, optimization, and characterization of a novel tea tree oil nanogel using response surface methodology. AB - PURPOSE: To develop and optimize nanoemulsion (NE)-based emulgel (EG) formulation as a potential vehicle for topical delivery of tea tree oil (TTO). METHODOLOGY: Central composite design was adopted for optimizing the processing conditions for NE preparation by high energy emulsification method viz. surfactant concentration, co-surfactant concentration, and stirring speed. The optimized NE was developed into emulgel (EG) using pH sensitive polymer Carbopol 940 and triethanolamine as alkalizer. The prepared EG was evaluated for its pH, viscosity, and texture parameters, ex vivo permeation at 37 degrees C and stability. Antimicrobial evaluation of EG in comparison to conventional gel and pure TTO was also carried out against selected microbial strains. RESULTS AND DISCUSSION: Optimized NE had particle size and zeta potential of 16.23 +/- 0.411 nm and 36.11 +/- 1.234 mV, respectively. TEM analysis revealed the spherical shape of droplets. The pH of EG (5.57 +/- 0.05 ) was found to be in accordance with the range of human skin pH. EG also illustrated efficient permeation (79.58 MUL/cm(2)) and flux value (JSS) of 7.96 MUL cm(2)/h through skin in 10 h. Viscosity and texture parameters, firmness (9.3 +/- 0.08 g), spreadability (2.26 +/- 0.06 mJ), extrudability (61.6 +/- 0.05 mJ), and adhesiveness (8.66 +/- 0.08 g) depict its suitability for topical application. Antimicrobial evaluation of EG with same amount of TTO as conventional gel revealed broader zones of growth inhibitions against all the selected microbial strains. Moreover, EG was also found to be nonirritant (PII 0.0833). These parameters were consistent over 90 d. CONCLUSION: TTO EG turned out to be a promising vehicle for the topical delivery of TTO with enhanced therapeutic efficacy. PMID- 26821209 TI - Long chain n-3 polyunsaturated fatty acids increase the efficacy of docetaxel in mammary cancer cells by downregulating Akt and PKCepsilon/delta-induced ERK pathways. AB - Taxanes can induce drug resistance by increasing signaling pathways such as PI3K/Akt and ERK, which promote survival and cell growth in human cancer cells. We have previously shown that long chain n-3 polyunsaturated fatty acids, such as docosahexaenoic acid (DHA, 22:6n-3) decrease resistance of experimental mammary tumors to anticancer drugs. Our objective was to determine whether DHA could increase tumor sensitivity to docetaxel by down-regulating these survival pathways. In docetaxel-treated MDA-MB-231 cells, phosphorylated-ERK1/2 levels were increased by 60% in membrane and nuclear compartments, compared to untreated cells. Our data showed that ERK1/2 activation depended on PKC activation since: i) enzastaurin (a pan-PKC inhibitor) blocked docetaxel-induced ERK1/2 phosphorylation ii) docetaxel increased PKC activity by 30% and phosphatidic acid level by 1.6-fold iii) inhibition of PKCepsilon and PKCdelta by siRNA resulted in reduced phosphorylated ERK1/2 levels. In DHA-supplemented cells, docetaxel was unable to increase PKCepsilon and delta levels in membrane and nuclear fractions, resulting in diminished ERK1/2 phosphorylation and increased docetaxel efficacy. Reduced membrane level of PKCepsilon and PKCdelta was associated with significant incorporation of DHA in all phospholipids, including phosphatidylcholine which is a major source of phosphatidic acid. Additionally, examination of the Akt pathway showed that DHA could repress docetaxel-induced Ser473Akt phosphorylation. In rat mammary tumors, dietary DHA supplementation during docetaxel chemotherapy repressed ERK and Akt survival pathways and in turn strongly improved taxane efficacy. The P-ERK level was negatively correlated with tumor regression. These findings are of potential clinical importance in treating chemotherapy-refractory cancer. PMID- 26821210 TI - The Halicylindramides, Farnesoid X Receptor Antagonizing Depsipeptides from a Petrosia sp. Marine Sponge Collected in Korea. AB - Three new structurally related depsipeptides, halicylindramides F-H (1-3), and two known halicylindramides were isolated from a Petrosia sp. marine sponge collected off the shore of Youngdeok-Gun, East Sea, Republic of Korea. Their planar structures were elucidated by extensive spectroscopic data analyses including 1D and 2D NMR data as well as MS data. The absolute configurations of halicylindramides F-H (1-3) were determined by Marfey's method in combination with Edman degradation. The absolute configurations at C-4 of the dioxyindolyl alanine (Dioia) residues of halicylindramides G (2) and H (3) were determined as 4S and 4R, respectively, based on ECD spectroscopy. The C-2 configurations of Dioia in 2 and 3 were speculated to both be 2R based on the shared biogenesis of the halicylindramides. Halicylindramides F (1), A (4), and C (5) showed human farnesoid X receptor (hFXR) antagonistic activities, but did not bind directly to hFXR. PMID- 26821211 TI - Sustained glucocorticoid exposure recruits cortico-limbic CRH signaling to modulate endocannabinoid function. AB - Sustained exposure to stress or corticosteroids is known to cause changes in brain endocannabinoid (eCB) signaling, such that tissue contents of the eCBs N arachidonylethanolamine (AEA) are generally reduced while 2-arachidonoylglycerol (2-AG) levels increase. These changes in eCB signaling are important for many of the aspects of chronic stress, such as anxiety, reward sensitivity and stress adaptation, yet the mechanisms mediating these changes are not fully understood. We have recently found that the stress-related neuropeptide corticotropin releasing hormone (CRH), acting through the CRH type 1 receptor (CRHR1), can reduce AEA content by increasing its hydrolysis by the enzyme fatty acid amide hydrolase (FAAH) as well as increase 2-AG contents. As extra-hypothalamic CRH is upregulated by chronic corticosteroid or stress exposure, we hypothesized that increased CRH signaling through CRHR1 contributes to the effects of chronic corticosteroid exposure on the eCB system within the amygdala and prefrontal cortex. Male rats were exposed to 7 days of systemic corticosterone capsules, with or without concurrent exposure to a CRHR1 antagonist, after which we examined eCB content. Consistent with previous studies in the amygdala, sustained corticosterone exposure increases CRH mRNA in the prefrontal cortex. As was shown previously, FAAH activity was increased and AEA contents were reduced within the amygdala and prefrontal cortex following chronic corticosterone exposure. Chronic corticosterone exposure also elevated 2-AG content in the prefrontal cortex but not the amygdala. These corticosteroid-driven changes were all blocked by systemic CRHR1 antagonism. Consistent with these data indicating sustained increases in CRH signaling can mediate the effects of chronic elevations in corticosteroids, CRH overexpressing mice also exhibited increased FAAH-mediated AEA hydrolysis in the amygdala and prefrontal cortex compared to wild type. CRH overexpression increased 2-AG content in the amygdala, but not the prefrontal cortex. These data indicate that chronic elevations in CRH signaling, as is seen following exposure to chronic elevations in corticosterone or stress, drive persistent changes in eCB function. As reductions in AEA signaling mediate the effects of CRH and chronic stress on anxiety, these data provide a mechanism linking these processes. PMID- 26821213 TI - Smoking prevalence in urban and rural populations: findings from California between 2001 and 2012. AB - BACKGROUND: Tobacco smoking and related health problems are still major public health concerns in the United States despite the declining smoking prevalence. OBJECTIVES: This study explored differences in smoking prevalence between urban and rural areas potentially relevant to tobacco control efforts in California. METHODS: Public use adult smoking data from the California Health Interview Survey (CHIS) between 2001 and 2011-2012 were analyzed. A total of 282 931 adults were surveyed across the six CHIS cycles. A ZIP code-based geographic classification (Urban, Second-City, Suburban, and Town/Rural) was used to examine the association between smoking prevalence and area of residency. RESULTS: The overall smoking prevalence in California decreased from 17.0% in 2001 to 13.8% in 2011-2012. Within each CHIS cycle, the Town/Rural areas had the highest smoking prevalence, followed by Urban and Second-City areas, and Suburban areas had the lowest. Pooled data from all CHIS cycles showed a similar pattern, with rates in Urban, Second-City, Suburban and Town/Rural areas being 15.2%, 15.2%, 13.1% and 17.3%, respectively. Weighted multivariate logistic regression analysis indicated significantly higher odds of smoking in Urban, Second-City and Town/Rural areas compared to Suburban areas (all adjusted odds ratios > 1.10), although this trend varied by race/ethnicity, being present in non-Hispanic Whites and not present in Hispanics. CONCLUSIONS: Town/Rural and Urban populations of California are consistently at higher risk of smoking than Suburban populations. These results indicate a need for population-specific tobacco control approaches that address the lifestyle, behavior, and education of disparate populations within the same state or region. PMID- 26821212 TI - Alcohol and tobacco consumption alter hypothalamic pituitary adrenal axis DNA methylation. AB - Alcohol and cigarette consumption have profound effects on genome wide DNA methylation and are common, often cryptic, comorbid features of many psychiatric disorders. This cryptic consumption is a possible impediment to understanding the biology of certain psychiatric disorders because if the effects of substance use are not taken into account, their presence may confound efforts to identify effects of other behavioral disorders. Since the hypothalamic pituitary adrenal (HPA) axis is known to be dysregulated in these disorders, we examined the potential for confounding effects of alcohol and cigarette consumption by examining their effects on peripheral DNA methylation at two key HPA axis genes, NR3C1 and FKBP5. We found that the influence of alcohol and smoke exposure is more prominent at the FKBP5 gene than the NR3C1 gene. Furthermore, in both genes, loci that were consistently significantly associated with smoking and alcohol consumption demethylated with increasing exposure. We conclude that epigenetic studies of complex disorders involving the HPA axis need to carefully control for the effects of substance use in order to minimize the possibility of type I and type II errors. PMID- 26821214 TI - Magnetic Propulsion of Microswimmers with DNA-Based Flagellar Bundles. AB - We show that DNA-based self-assembly can serve as a general and flexible tool to construct artificial flagella of several micrometers in length and only tens of nanometers in diameter. By attaching the DNA flagella to biocompatible magnetic microparticles, we provide a proof of concept demonstration of hybrid structures that, when rotated in an external magnetic field, propel by means of a flagellar bundle, similar to self-propelling peritrichous bacteria. Our theoretical analysis predicts that flagellar bundles that possess a length-dependent bending stiffness should exhibit a superior swimming speed compared to swimmers with a single appendage. The DNA self-assembly method permits the realization of these improved flagellar bundles in good agreement with our quantitative model. DNA flagella with well-controlled shape could fundamentally increase the functionality of fully biocompatible nanorobots and extend the scope and complexity of active materials. PMID- 26821215 TI - NOS1 and SNAP25 polymorphisms are associated with Attention-Deficit/Hyperactivity Disorder symptoms in adults but not in children. AB - Several investigations documented that Attention-Deficit/Hyperactivity Disorder (ADHD) is better conceptualized as a dimensional disorder. At the same time, the disorder seems to have different neurobiological underpinnings and phenotypic presentation in children compared to adults. Neurodevelopmental genes could explain, at least partly these differences. The aim of the present study was to examine possible associations between polymorphisms in SNAP25, MAP1B and NOS1 genes and ADHD symptoms in Brazilian samples of children/adolescents and adults with ADHD. The youth sample consisted of 301 patients whereas the adult sample comprises 485 individuals with ADHD. Diagnoses of ADHD and comorbidities were based on the Diagnostic and Statistical Manual of Mental Disorders-4th edition criteria. The Swanson, Nolan and Pelham Scale-Version IV (SNAP-IV) was applied by psychiatrists blinded to genotype. The total SNAP-IV scores were compared between genotypes. Impulsivity SNAP-IV scores were also compared according to NOS1 genotypes. Adult patients homozygous for the C allele at SNAP25 rs8636 showed significantly higher total SNAP-IV scores (F = 11.215; adjusted P-value = 0.004). Impulsivity SNAP-IV scores were also significantly different according to NOS1 rs478597 polymorphisms in adults with ADHD (F = 6.282; adjusted P-value = 0.026). These associations were not observed in children and adolescents with ADHD. These results suggest that SNAP25 and NOS1 genotypes influence ADHD symptoms only in adults with ADHD. Our study corroborates previous evidences for differences in the genetic contribution to adult ADHD compared with childhood ADHD. PMID- 26821216 TI - A Mother's Gift: Congenital Transmission of Trypanosoma and Leishmania Species. PMID- 26821217 TI - Single institution experience of paediatric melanoma in Victoria, Australia. AB - BACKGROUND/OBJECTIVES: Paediatric melanoma is an uncommon presentation of melanoma that accounts for 3% of all paediatric cancers. The objective was to describe a series of paediatric melanoma cases presenting to a state-wide tertiary referral service over the past 19 years. METHODS: A search of the Victorian Melanoma Service database was performed to identify all patients under the age of 20 years diagnosed with melanoma from 1994 to 2013. Histological, demographic and phenotypical information for each patient was collected. Patients were matched against the Victorian Death Registry to identify those who had died. Fisher's exact test was used to examine associations. Melanoma-specific survival was estimated using the Kaplan-Meier method. RESULTS: A total of 65 paediatric melanoma patients were included for analysis, in whom 72.3% of melanomas were diagnosed when they were 16-19 years of age with a mean age at diagnosis of 16 years. The mean Breslow thickness was 1.4 mm. It was greatest (3.4 mm) in the youngest age group (< 12 years of age). Ten patients developed nodal metastatic disease, eight of which progressed to visceral metastatic disease. The 5-year melanoma-specific survival rate was 96.8%. CONCLUSION: This is the first descriptive epidemiological study of paediatric melanoma in Victoria. Further large, population-based, multi-institutional studies of paediatric melanoma are warranted to provide a clearer understanding of this group of melanoma patients. PMID- 26821218 TI - Mechanistic Study of Human Glucose Transport Mediated by GLUT1. AB - The glucose transporter 1 (GLUT1) belongs to the major facilitator superfamily (MFS) and is responsible for the constant uptake of glucose. However, the molecular mechanism of sugar transport remains obscure. In this study, homology modeling and molecular dynamics (MD) simulations in lipid bilayers were performed to investigate the combination of the alternate and multisite transport mechanism of glucose with GLUT1 in atomic detail. To explore the substrate recognition mechanism, the outward-open state human GLUT1 homology model was generated based on the template of xylose transporter XylE (PDB ID: 4GBZ), which shares up to 29% sequence identity and 49% similarity with GLUT1. Through the MD simulation study of glucose across lipid bilayer with both the outward-open GLUT1 and the GLUT1 inward-open crystal structure, we investigated six different conformational states and identified four key binding sites in both exofacial and endofacial loops that are essential for glucose recognition and transport. The study further revealed that four flexible gates consisting of W65/Y292/Y293-M420/TM10b-W388 might play important roles in the transport cycle. The study showed that some side chains close to the central ligand binding site underwent larger position changes. These conformational interchanges formed gated networks within an S shaped central channel that permitted staged ligand diffusion across the transporter. This study provides new inroads for the understanding of GLUT1 ligand recognition paradigm and configurational features which are important for molecular, structural, and physiological research of the MFS members, especially for GLUT1-targeted drug design and discovery. PMID- 26821222 TI - Bone Health: Not Just for the Elderly. PMID- 26821219 TI - Hepatotoxicity of piperazine designer drugs: up-regulation of key enzymes of cholesterol and lipid biosynthesis. AB - The piperazine derivatives most frequently consumed for recreational purposes are 1-benzylpiperazine, 1-(3,4-methylenedioxybenzyl) piperazine, 1-(3 trifluoromethylphenyl) piperazine and 1-(4-methoxyphenyl) piperazine. Generally, they are consumed as capsules, tablets or pills but also in powder or liquid forms. Currently, the precise mechanism by which piperazine designer drugs induce hepatotoxicity and whether they act by a common pathway is unclear. To answer this question, we performed a gene array study with rat hepatocytes incubated with the four designer drugs. Non-cytotoxic concentrations were chosen that neither induce a decrease in reduced glutathione or ATP depletion. Analysis of the gene array data showed a large overlap of gene expression alterations induced by the four drugs. This 'piperazine designer drug consensus signature' included 101 up-regulated and 309 down-regulated probe sets (p < 0.05; FDR adjusted). In the up-regulated genes, GO groups of cholesterol biosynthesis represented a dominant overrepresented motif. Key enzymes of cholesterol biosynthesis up regulated by all four piperazine drugs include sterol C4-methyloxidase, isopentyl diphosphate-Delta-isomerase, Cyp51A1, squalene epoxidase and farnesyl diphosphate synthase. Additionally, glycoprotein transmembrane nmb, which participates in cell adhesion processes, and fatty acid desaturase 1, an enzyme that regulates unsaturation of fatty acids, were also up-regulated by the four piperazine designer drugs. Regarding the down-regulated probe sets, only one gene was common to all four piperazine derivatives, the betaine-homocysteine-S-methyltransferase 2. Analysis of transcription factor binding sites of the 'piperazine designer drug consensus signature' identified the sterol regulatory element binding protein (SREBP-1) as strongly overrepresented in the up-regulated genes. SREBP transcription factors are known to regulate multiple genes of cholesterol metabolism. In conclusion, the present study shows that piperazine designer drugs act by up-regulating key enzymes of cholesterol biosynthesis which is likely to increase the risk of phospholipidosis and steatosis. PMID- 26821223 TI - Challenges in Reverse Shoulder Arthroplasty: Addressing Glenoid Bone Loss. AB - Reverse shoulder arthroplasty (RSA) was designed for the treatment of elderly patients with cuff tear arthropathy. Because of its success, the indications for RSA have expanded beyond cuff tear arthropathy to include acute fractures, fracture sequelae, massive rotator cuff tears, inflammatory arthritis, and revision shoulder arthroplasty. Consequently, the number of RSAs performed has increased steadily. Glenoid bone loss is not uncommon in patients undergoing primary or revision RSA. Failure to appreciate and address glenoid bone loss during RSA can lead to improper baseplate positioning and early failure or complications such as dislocation or scapular notching. The authors present a review of the current literature as well as recommended strategies for characterization of glenoid bone loss and preferred surgical techniques for addressing bone loss during RSA. PMID- 26821224 TI - Early Ankle Mobilization Promotes Healing in a Rabbit Model of Achilles Tendon Rupture. AB - The use of early mobilization of the ankle joint without orthosis in the treatment of Achilles tendon rupture has been advocated as the optimal management. The goal of this study was to compare outcomes in a postoperative rabbit model of Achilles tendon rupture between early mobilization and immobilized animals using a differential proteomics approach. In total, 135 rabbits were randomized into the control group (n=15), the postoperative cast immobilization (PCI) group (n=60), and the early mobilization (EM) group (n=60). A rupture of the Achilles tendon was created in each animal model and repaired microsurgically, and tendon samples were removed at 3, 7, 14, and 21 days postoperatively. Proteins were separated using 2-dimensional polyacrylamide gel electrophoresis and identified using peptide mass fingerprinting, tandem mass spectrometry, NCBI database searches, and bioinformatics analyses. A series of differentially expressed proteins were identified between groups, some of which may play an important role in Achilles tendon healing. Notable candidate proteins that were upregulated in the EM group were identified, such as CRMP-2, galactokinase 1, tropomyosin-4, and transthyretin. The healing of ruptured Achilles tendons appears to be affected at the level of protein expression with the use of early mobilization. The classic postoperative treatment of Achilles tendon rupture with an orthosis ignored the self-protecting instinct of humans. With a novel operative technique, the repaired tendon can persist the load that comes from traction in knee and ankle joint functional movement. In addition, kinesitherapy provided an excellent experimental outcome via a mechanobiological mechanism. PMID- 26821225 TI - Dose-related effects of metformin on acid-base balance and renal function in patients with diabetes who develop acute renal failure: a cross-sectional study. AB - AIMS: The role of metformin in the development of lactic acidosis (LA) in the setting of acute renal failure (ARF) is debated. Moreover, recent experiments suggested that metformin can also be nephrotoxic, but little clinical data exist about this topic. We sought to investigate these possible associations in a large cohort of patients with diabetes who developed ARF. METHODS: We analyzed data from patients with diabetes admitted to our emergency department between 2007 and 2011 with ARF and a previously normal renal function (n = 126). We compared acid base balance and renal function of patients taking metformin (n = 74) with patients not taking it (n = 52). RESULTS: Patients taking metformin had decreased pH (7.31 +/- 0.16 vs 7.39 +/- 0.11, p = 0.008) and higher lactates (4.54 +/- 4.30 vs 1.71 +/- 1.14 mmol/L, p < 0.001). Both acidosis (pH < 7.35) and LA (lactates >5 mmol/L and pH < 7.35) were more frequently observed in this group (p = 0.0491 and p < 0.001, respectively). Multivariate analysis ruled out the role of some possible confounders, especially decreased renal function. The influence of metformin on pH and lactates grew significantly with higher doses of the drug (p = 0.259 and p = 0.092 for <1 g/day, p = 0.289 and p < 0.001 for 1-2 g/day, p = 0.009 and p < 0.001 for 2-3 g/day, for pH and lactates, respectively). Metformin influenced creatinine levels in a dose-related manner as well (p = 0.925 for <1 g/day, p = 0.033 for 1-2 g/day, p < 0.001 for 2-3 g/day). CONCLUSIONS: In patients with diabetes who were admitted to our emergency department with ARF, the use of metformin was associated in a dose-related fashion with both LA and worse renal function. PMID- 26821226 TI - Ultrasound associated with caffeine increases basal and beta-adrenoceptor response in adipocytes isolated from subcutaneous adipose tissue in pigs. AB - BACKGROUND: The topical use of caffeine has been indicated for the lipodystrophies treatment as it promotes increased lipolysis. Ultrasound (US) is often used in cutaneous diseases, esthetic conditions, and as a skin permeation enhancer. OBJECTIVE: We investigate the lipolytic response of adipocytes isolated from subcutaneous adipose pigs tissue subjected to treatment with topical application of phonophoresis associated with caffeine. METHOD: We treated dorsal regions of pigs (Landrace * Large White, 35 days, 15 kg, n = 6) daily for 15 days with gel, gel + US [3 MHz, continuous, 0.2 Wcm(2), 1 min/cm(2), in total 2 min], gel + caffeine (5%w/w), and gel + caffeine + US. We used a fifth untreated region as control. Twenty-four hours after the last application, we isolated the adipocytes of each treated area and quantified the basal and stimulated lipolytic responses to isoprenaline. The results, in MUmol glycerol/10(6)cells/60 min, were analyzed with analysis of variance or ANOVA followed by Newman-Keuls test. The value of p < 0.05 was indicative of statistical difference. RESULTS: Only the adipocytes isolated from the area treated with caffeine + US showed increased basal lipolysis (0.76 +/- 0.26; p = 0.0276) and maximal isoprenaline stimulation (0.38 +/- 0.15, p = 0.0029) compared with the other areas. CONCLUSION: The results demonstrate that increased lipolysis of caffeine + US is due to an increase in basal and beta-adrenoceptor response by caffeine, and caffeine's effect is local, avoiding unwanted effects. PMID- 26821227 TI - Interaction of low dose of fish oil and glucocorticoids on insulin sensitivity and lipolysis in healthy humans: A randomized controlled study. AB - SCOPE: This study examined the interaction of fish oil (FO) with dexamethasone on glucose and lipid metabolisms in healthy subjects. METHODS AND RESULTS: The study included two consecutive parts. Part A (randomized) in 16 subjects studied the effects of dexamethasone (2 days, 2 mg/day) versus placebo (lactose), part B (two parallel subgroups of eight) studied the interaction of FO (3 wk, 840 mg/day of EPA + DHA) with dexamethasone. Insulin sensitivity of lipolysis (d5-glycerol infusion + microdialysis), endogenous glucose production, and muscle glucose uptake were assessed by a three-step hot insulin clamp and substrate oxidation by indirect calorimetry. Dexamethasone induced liver and peripheral insulin resistance, an increase in fat oxidation, and a decrease in suppression of plasma nonesterified fatty acids (NEFAs). FO amplified the effects of dexamethasone by increasing liver and muscle insulin resistance, by reducing suppression of plasma NEFAs and fat oxidation and by increasing adipose tissue (AT) lipolysis. CONCLUSION: FO, given at a moderate dose in healthy subjects prior to a very short-term (2 days) low dose of a synthetic glucocorticoid, worsened its deleterious effects on insulin sensitivity. The enhancing effect of FO on fat oxidation and AT lipolysis might be a protective effect toward an increase in fat mass. PMID- 26821228 TI - Critical Parameters for Efficient Sonication and Improved Chromatin Immunoprecipitation of High Molecular Weight Proteins. AB - Solubilization of cross-linked cells followed by chromatin shearing is essential for successful chromatin immunoprecipitation (ChIP). However, this task, typically accomplished by ultrasound treatment, may often become a pitfall of the process, due to inconsistent results obtained between different experiments under seemingly identical conditions. To address this issue we systematically studied ultrasound-mediated cell lysis and chromatin shearing, identified critical parameters of the process and formulated a generic strategy for rational optimization of ultrasound treatment. We also demonstrated that whereas ultrasound treatment required to shear chromatin to within a range of 100-400 bp typically degrades large proteins, a combination of brief sonication and benzonase digestion allows for the generation of similarly sized chromatin fragments while preserving the integrity of associated proteins. This approach should drastically improve ChIP efficiency for this class of proteins. PMID- 26821229 TI - Detection and signal amplification in zebrafish RNA FISH. AB - In situ hybridization (ISH) has become an invaluable tool for the detection of RNA in cells, tissues and organisms. Due to improvements in target and signal amplification and in probe design remarkable progress has been made concerning sensitivity, specificity and resolution of chromogenic and fluorescent ISH (FISH). These advancements allow for exquisite cellular and sub-cellular resolution and for detecting multiple RNA species at a time by multiplexing. In zebrafish (F)ISH non-enzymatic and enzymatic amplification systems have been employed to obtain enhanced signal intensities and signal-to-noise ratios. These amplification strategies include branched DNA-based RNAscope and in situ hybridization chain reaction (HCR) techniques, as well as alkaline phosphatase (AP)- and horseradish peroxidase (PO)-based immunoassays. For practical application, we provide proven multiplex FISH protocols for AP- and PO-based visualization of mRNAs at high resolution. The protocols take advantage of optimized tyramide signal amplification (TSA) conditions of the PO assay and long lasting high signal-to-noise ratio of the AP reaction, thereby enabling detection of less abundant transcripts. PMID- 26821230 TI - Cation-pi Interaction Induced Folding of AAB-Type Collagen Heterotrimers. AB - Collagen is the most predominant component of the extracellular matrix. Natural collagens consist of all identical (AAA, homotrimer), two different (AAB, heterotrimer), or three different (ABC, heterotrimer) peptide chains. Many natural collagens are either AAB- or ABC-type heterotrimers, making heterotrimeric helices better mimics for studying collagen structures in nature. We prepared collagen-mimetic peptides containing cationic (Arg) or aromatic (Phe, Tyr) residues to explore collagen heterotrimer folding via cation-pi interactions. Circular dichroism, differential scanning calorimetry, and nuclear magnetic resonance (NMR) measurements showed that the interchain cation-pi interactions between cationic and aromatic peptides could induce AAB-type heterotrimer formation. By controlling the mixing molar ratios of cationic and aromatic peptides in solution, we could obtain the heterotrimers with various compositions. We demonstrate the effectiveness of cation-pi interactions as a force to fold collagen heterotrimers. PMID- 26821231 TI - Critical Slowing Down as a Personalized Early Warning Signal for Depression. PMID- 26821232 TI - Disruption of the stress response in wastewater treatment works effluent-exposed three-spined sticklebacks persists after translocation to an unpolluted environment. AB - The hypothalamic-pituitary-adrenal/interrenal (HPA/I) axis plays a key role in responding to biotic and abiotic challenges in all vertebrates. Recent studies have shown that the apical response of the HPI axis to stressors in three-spined sticklebacks varies in proportion to the concentration of wastewater treatment works (WWTW) effluent to which the fish are exposed. This study was conducted to determine whether between-site variation in stress responsiveness among WWTW effluent-exposed sticklebacks is persistent or reversible. Sticklebacks from eight sites in north-west England affected by WWTW effluent and exhibiting between-population variation in HPI axis reactivity, were moved to a clean-water aquarium environment. After five months in the contaminant-free environment the responsiveness of these fish to a standardised stressor was determined, by measuring the rate of stress-induced cortisol release across the gills, and compared with the responses of fish newly sampled from the eight original capture sites. Inter-site differences in the reactivity of the HPI axis, proportional to the effluent concentration at each site, persisted among the translocated female sticklebacks for at least 5 months. In male fish however, the direct relationship between stress responsiveness and site-specific effluent was not evident 5 months post-translocation. These results support previous observations that the HPA/I axis, a non-reproductive endocrine system, is vulnerable to modulation by anthropogenic factors in fish and show for the first time that, in female fish at least, this modulation is not transient. The mechanisms underlying these observations, and the implications for the fitness and resilience of affected populations, requires investigation. PMID- 26821233 TI - Effects of an insect growth regulator and a solvent on honeybee (Apis mellifera L.) brood development and queen viability. AB - Honeybee toxicology is complex because effects on individual bees are modulated by social interactions between colony members. In the present study, we applied high doses of the insect growth regulator fenoxycarb to honeybee colonies to elucidate a possible interplay of individually- and colony-mediated effects regarding honey bee toxicology. Additionally, possible effects of the solvent dimethyl sulfoxide (DMSO) were assessed. We conducted studies on egg hatching and brood development to assess brood care by nurse bees as well as queen viability. Egg hatching was determined by the eclosion rate of larvae from eggs originating from colonies (i) treated with sugar syrup only, (ii) treated with sugar syrup containing DMSO and (iii) treated with sugar syrup containing fenoxycarb (dissolved in DMSO). To evaluate brood development, combs with freshly laid eggs were reciprocally transferred between colonies, and development of brood was examined in the recipient hive. Brood reared inside DMSO- and fenoxycarb-treated colonies as well as brood from DMSO- and from fenoxycarb-exposed queens showed higher mortality than brood not exposed to the chemicals. No differences were found in egg hatching among the treatments, but there was a higher variability of eclosion rates after queens were exposed to fenoxycarb. We also observed queen loss and absconding of whole colonies. Based on our results we infer that fenoxycarb has queen- as well as nurse bee-mediated effects on brood quality and development which can lead to the queen's death. There also is an effect of DMSO on the nurse bees' performance that could disturb the colony's equilibrium, at least for a delimited timespan. PMID- 26821234 TI - 17beta-estradiol suppresses hyperoxia-induced apoptosis of oligodendrocytes through paired-immunoglobulin-like receptor B. AB - Hyperoxia is a high risk factor for neurodevelopmental disorders and can cause nerve cell death. 17beta-Estradiol (E2) has been demonstrated as a neuroprotective agent. In the present study, the effect of hyperoxia on rat oligodendrocyte precursor cells (OPCs) in vivo and the neuroprotective effects of E2 on these cells were investigated. OPCs were treated with various concentrations of E2 and were harvested for reverse transcription-quantitiative polymerase chain reaction (RT-qPCR) analysis at various time-points. RT-qPCR analysis demonstrated that paired immunoglobin-like receptor B (PriB) PriB mRNA expression levels were markedly decreased following treatment with 10(-6), 10(-7) and 10(-8) M E2. Cells treated with 10(-7) M E2 for 24 h were selected for subsequent experiments. PriB was silenced with small interfering (si)RNA and the effects of E2 treatment and silencing of PriB on the viability and apoptosis of OPCs under hyperoxic stimulation was detected using 3-(4,5-dimethyl-2-thiazolyl) 2,5-diphenyl-2-H-tetrazoliu-bromide (MTT) assay and flow cytometry analysis. The results revealed that hyperoxia induced apoptosis in OPCs and decreased their viability. Hyperoxia also induced the expression of caspases-3 and -8, and Fas cell surface death receptor (Fas). E2 treatment markedly downregulated the expression of PirB. E2 treatment or PirB silencing markedly decreased hyperoxia induced apoptosis, increased cell viability and decreased the expression of caspases-3 and -8, and Fas in OPCs, indicating that E2 protects OPCs from hyperoxia-induced apoptosis, predominantly through the downregulation of PirB The results of the present study provide a theoretical basis for the reasonable use of oxygen in Neonatal Intensive Care Units. PMID- 26821235 TI - HIV-infected presumptive tuberculosis patients without tuberculosis: How many are eligible for antiretroviral therapy in Karnataka, India? AB - For certain subgroups within people living with the human immunodeficiency virus (HIV) [active tuberculosis (TB), pregnant women, children <5years old, and serodiscordant couples], the World Health Organization recommends antiretroviral therapy (ART) irrespective of CD4 count. Another subgroup which has received increased attention is "HIV-infected presumptive TB patients without TB". In this study, we assess the proportion of HIV-infected presumptive TB patients eligible for ART in Karnataka State (population 60million), India. This was a cross sectional analysis of data of HIV-infected presumptive TB patients diagnosed in May 2015 abstracted from national TB and HIV program records. Of 42,585 presumptive TB patients, 28,964 (68%) were tested for HIV and 2262 (8%) were HIV positive. Of the latter, 377 (17%) had active TB. Of 1885 "presumptive TB patients without active TB", 1100 (58%) were already receiving ART. Of the remaining 785 who were not receiving ART, 617 (79%) were assessed for ART eligibility and of those, 548 (89%) were eligible for ART. About 90% of "HIV infected presumptive TB patients without TB" were eligible for ART. This evidence supports a public health approach of starting all "HIV-infected presumptive TB patients without TB" on ART irrespective of CD4 count in line with global thinking about 'test and treat'. PMID- 26821236 TI - Multivariate Calibration Approach for Quantitative Determination of Cell-Line Cross Contamination by Intact Cell Mass Spectrometry and Artificial Neural Networks. AB - Cross-contamination of eukaryotic cell lines used in biomedical research represents a highly relevant problem. Analysis of repetitive DNA sequences, such as Short Tandem Repeats (STR), or Simple Sequence Repeats (SSR), is a widely accepted, simple, and commercially available technique to authenticate cell lines. However, it provides only qualitative information that depends on the extent of reference databases for interpretation. In this work, we developed and validated a rapid and routinely applicable method for evaluation of cell culture cross-contamination levels based on mass spectrometric fingerprints of intact mammalian cells coupled with artificial neural networks (ANNs). We used human embryonic stem cells (hESCs) contaminated by either mouse embryonic stem cells (mESCs) or mouse embryonic fibroblasts (MEFs) as a model. We determined the contamination level using a mass spectra database of known calibration mixtures that served as training input for an ANN. The ANN was then capable of correct quantification of the level of contamination of hESCs by mESCs or MEFs. We demonstrate that MS analysis, when linked to proper mathematical instruments, is a tangible tool for unraveling and quantifying heterogeneity in cell cultures. The analysis is applicable in routine scenarios for cell authentication and/or cell phenotyping in general. PMID- 26821237 TI - Analysis and Characterization of Staphylococcus aureus Small Colony Variants Isolated From Cystic Fibrosis Patients in Austria. AB - Cystic fibrosis (CF) is the most common hereditary lung disease in the Caucasian population, characterized by viscous bronchial secretion, consecutive defective mucociliary clearance, and unavoidable colonization with microorganisms. Besides Pseudomonas aeruginosa, Staphylococcus aureus is the most common bacterial species colonizing the CF respiratory tract. Under antibiotic pressure S. aureus is able to switch to small colony variants (SCV). These small colony variants can invade epithelial cells, overcome antibiotic therapy inside the cells and can be the starting point for extracellular recolonization. The aim of the present study was the isolation and characterization of S. aureus small colony variants from Austrian cystic fibrosis patients. Samples collected from 147 patients were screened for the presence of S. aureus wild-type and small colony variants. Antibiotic susceptibility testing and determination of the small colony variants causing auxotrophism were performed. Wild-type isolates were assigned to corresponding small colony variants with spa typing. In total, 17 different small colony variant isolates and 12 corresponding wild-type isolates were obtained. 13 isolates were determined thymidine auxotroph, 2 isolates were auxotroph for hemin, and none of the tested isolates was auxotroph for both, respectively. The presence of SCVs is directly related to a poor clinical outcome, therefore a monitoring of SCV prevalence is recommended. This study revealed rather low SCV ratios in CF patients compared to other countries. PMID- 26821238 TI - Effects of Bacillus subtilis natto and Different Components in Culture on Rumen Fermentation and Rumen Functional Bacteria In Vitro. AB - This study was to investigate the effects of live or autoclaved Bacillus subtilis natto, their fermented products and media on rumen fermentation and rumen functional bacteria in vitro. Rumen fluid from three multiparous lactating Holstein cows was combined and transferred into serum bottles after diluted. Fifteen serum bottles were divided into five treatments, which were designed as following: CTR (the fermentation of 0.5 g TMR and ruminal fluids from dairy cows), LBS (CTR plus a minimum of 10(11) cfu live Bacillus subtilis natto), ABS (CTR plus a minimum of 10(11) cfu autoclaved Bacillus subtilis natto), BSC (CTR plus 1 ml Bacillus subtilis natto fermentation products without bacteria), and BSM (CTR plus 1 ml liquid fermentation medium). When separated from the culture, live Bacillus subtilis natto individually increased the concentrations of ammonia N (P < 0.01), MCP production (P < 0.01), and tended to elevate total VFA (P = 0.07), but decreased the ratio of acetate and propionate (P < 0.01). Autoclaved Bacillus subtilis natto has the similar function with the live bacteria except for the ratio of acetate and propionate. Except B. fibrisolvens, live or autoclaved Bacillus subtilis natto did not influence or decreased the 16S rRNA gene quantification of the detected bacteria. BSC and BSM altered the relative expression of certain functional bacteria in the rumen. These results indicated that it was Bacillus subtilis natto thalli that played the important role in promoting rumen fermentation when applied as a probiotic in dairy ration. PMID- 26821239 TI - The Bioinformatics Report of Mutation Outcome on NADPH Flavin Oxidoreductase Protein Sequence in Clinical Isolates of H. pylori. AB - frxA gene has been implicated in the metronidazole nitro reduction by H. pylori. Alternatively, frxA is expected to contribute to the protection of urease and to the in vivo survival of H. pylori. The aim of present study is to report the mutation effects on the frxA protein sequence in clinical isolates of H. pylori in our community. Metronidazole resistance was proven in 27 of 48 isolates. glmM and frxA genes were used for molecular confirmation of H. pylori isolates. The primer set for detection of whole sequence of frxA gene for the effect of mutation on protein sequence was used. DNA and protein sequence evaluation and analysis were done by blast, Clustal Omega, and T COFFEE programs. Then, FrxA protein sequences from six metronidazole-resistant clinical isolates were analyzed by web-based bioinformatics tools. The result of six metronidazole resistant clinical isolates in comparison with strain 26695 showed ten missense mutations. The result with the STRING program revealed that no change was seen after alterations in these sequences. According to consensus data involving four methods, residue substitutions at 40, 13, and 141 increase the stability of protein sequence after mutation, while other alterations decrease. Residue substitutions at 40, 43, 141, 138, 169, and 179 are deleterious, while, V7I, Q10R, V34I, and V96I alterations are neutral. As FrxA contribute to survival of bacterium and in regard to the effect of mutations on protein function, it might affect the survival and bacterium phenotype and it need to be studied more. Also, none of the stability prediction tool is perfect; iStable is the best predictor method among all methods. PMID- 26821240 TI - Impact of topical 5% lidocaine-medicated plasters on sleep and quality of life in patients with postherpetic neuralgia. AB - AIM: To determine the impact of 5% lidocaine-medicated plasters on sleep, quality of life and pain in 265 patients with postherpetic neuralgia (PHN). PATIENTS & METHODS: An 8-week, open-label arm of a double-blind controlled withdrawal study. RESULTS: Patients treated with 5% lidocaine had less trouble falling asleep, used less sleep medication, had fewer awakenings due to pain at night or in the morning and their perception of quality of life was improved. The 15 pain descriptors in the Short-Form McGill Pain Questionnaire were improved from baseline to week 8, with a decrease in the proportion of patients reporting 'severe' pain and an increase in the number reporting 'none/mild' pain. CONCLUSION: 5% lidocaine-medicated plasters provide benefits beyond pain relief for patients with postherpetic neuralgia. PMID- 26821242 TI - The power of subliminal and supraliminal eye contact on social decision making: An individual-difference perspective. AB - We conducted two experiments to explore how social decision making is influenced by the interaction of eye contact and social value orientation (SVO). Specifically, participants with a Prosocial (Prosocials) or a Proself (Proselfs) SVO played Prisoner Dilemma games with a computer partner following supraliminal (Experiment 1) and subliminal (Experiment 2) direct gaze from that partner. Results showed that participants made more cooperative decisions after supraliminal eye contact than no eye contact, and the effect only existed for the Prosocials but not for the Proselfs. Nevertheless, when the computer partner made a subliminal eye contact with the participants, although more cooperative choices were found among the Prosocials following subliminal eye contact, relative to no contact, the Proselfs demonstrated reduced cooperation rates. These findings suggest that Prosocials and Proselfs interpreted eye contact in distinct ways at different levels of awareness, which led to various social decision making. PMID- 26821243 TI - Conflict in the kitchen: Contextual modulation of responsiveness to affordances. AB - Recently, human behavior has been considered the product of continuous interactions between perception, cognition and action in which "affordances" (action possibilities the environment has to offer) play an important role. Converging evidence suggests that multiple action possibilities simultaneously compete for further processing, while external and internal factors (e.g., incoming sensory information, predictions) bias this competition. In the present study we used a stop-task to investigate whether context is able to modulate the strength of the responsiveness to affordances. We therefore placed participants in an actual kitchen and workshop during electroencephalographic recordings. A faster response to context congruent objects demonstrated that the direct surrounding is able to affect responsiveness to affordances. In addition, when responses needed to be withheld, context congruent objects evoked greater response conflict as indicated by an enhanced N2 Event Related Potential (ERP) component. PMID- 26821244 TI - Medial orbital gyrus modulation during spatial perspective changes: Pre- vs. post 8 weeks mindfulness meditation. AB - Mindfulness meditation exercises the ability to shift to an "observer perspective". That means learning to observe internally and externally arising stimulations in a detached perspective. Both before and after attending a 8-weeks mindfulness training (MT) participants underwent an fMRI experiment (serving as their own internal control) and solved a own-body mental transformation task, which is used to investigate embodiment and perspective taking (and an non-bodily mental transformation task as control). We found a stimulus*time-points interaction: the own-body mental transformation task (vs. non-bodily) in the post (vs. pre-MT) significantly increased activations in the medial orbital gyrus. The signal change in the right medial orbital gyrus significantly correlated with changes in a self-maturity personality scale. A brief MT caused increased activation in areas involved in self related processing and person perspective changes, together with an increase in self-maturity, consistently with the aim of mindfulness meditation that is exercising change in self perspective. PMID- 26821245 TI - Oral exposure to mineral oils: Is there an association with immune perturbation and autoimmunity? AB - Mineral oils is a generic term that describes a category of petroleum products, that may include lubricating base oils and highly refined base oils. Parenteral exposure of rodents to certain mineral oil hydrocarbons has been reported to induce immune perturbation associated with the development of autoimmune responses. Consumers are exposed to a variety of mineral oil hydrocarbons via food and food contaminants, and in particular via food packaging. It is relevant, therefore, to consider whether dietary exposure to mineral oils results in similar effects; and that is the purpose of this article. There is no evidence that oral or dietary exposure of experimental animals to mineral oils will induce autoimmune responses, and the information that is available indicates that dietary exposure does not provoke such responses. There are epidemiological reports that suggest an association between mineral oils and autoimmunity in humans. However, the presumption in such instances is of high levels of exposure by inhalation or via the skin, and by reference to the data available from animal studies it is probable that dietary exposure would be ineffective. PMID- 26821241 TI - Cerebellar ataxias: beta-III spectrin's interactions suggest common pathogenic pathways. AB - Spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of disorders all characterised by postural abnormalities, motor deficits and cerebellar degeneration. Animal and in vitro models have revealed beta-III spectrin, a cytoskeletal protein present throughout the soma and dendritic tree of cerebellar Purkinje cells, to be required for the maintenance of dendritic architecture and for the trafficking and/or stabilisation of several membrane proteins: ankyrin-R, cell adhesion molecules, metabotropic glutamate receptor-1 (mGluR1), voltage gated sodium channels (Nav ) and glutamate transporters. This scaffold of interactions connects beta-III spectrin to a wide variety of proteins implicated in the pathology of many SCAs. Heterozygous mutations in the gene encoding beta III spectrin (SPTBN2) underlie SCA type-5 whereas homozygous mutations cause spectrin associated autosomal recessive ataxia type-1 (SPARCA1), an infantile form of ataxia with cognitive impairment. Loss-of beta-III spectrin function appears to underpin cerebellar dysfunction and degeneration in both diseases resulting in thinner dendrites, excessive dendritic protrusion with loss of planarity, reduced resurgent sodium currents and abnormal glutamatergic neurotransmission. The initial physiological consequences are a decrease in spontaneous activity and excessive excitation, likely to be offsetting each other, but eventually hyperexcitability gives rise to dark cell degeneration and reduced cerebellar output. Similar molecular mechanisms have been implicated for SCA1, 2, 3, 7, 13, 14, 19, 22, 27 and 28, highlighting alterations to intrinsic Purkinje cell activity, dendritic architecture and glutamatergic transmission as possible common mechanisms downstream of various loss-of-function primary genetic defects. A key question for future research is whether similar mechanisms underlie progressive cerebellar decline in normal ageing. PMID- 26821246 TI - Preliminary evaluation of photodynamic activity of manuka honey. PMID- 26821247 TI - Community-based intervention for depression management at the primary care level in Ha Nam Province, Vietnam: a cluster-randomised controlled trial. AB - OBJECTIVE: To evaluate the effectiveness of an intervention including psychoeducation and yoga for depression management at the primary healthcare level in one district in the Ha Nam province, Vietnam. METHOD: The Patient Health Questionnaire-9 (PHQ-9) was used for depression screening and follow-up. Screened patients were further diagnosed with the Mini-International Neuropsychiatric Diagnostic Interview, by a trained general doctor. A linear regression model, adjusted for age, gender and baseline PHQ-9 score was used to assess whether the intervention leads to decreased depression severity compared to standard care in the control communes. RESULTS: Both groups had similar PHQ-9 scores at baseline. The intervention group had on average significantly lower PHQ-9 scores after the intervention than the control group. Almost half of the patients in the intervention group recovered from depression, whereas nobody did in the control group. CONCLUSION: The results indicate that the intervention can be more effective than standard care in treating depression. The mean change of the PHQ-9 score after the intervention is deemed to be of clinical relevance. PMID- 26821249 TI - Associations between Neighborhood Characteristics, Well-Being and Health Vary over the Life Course. AB - BACKGROUND: Neighborhood characteristics are important determinants of individual health and well-being. For example, characteristics such as noise and pollution affect health directly, while other characteristics affect health and well-being by either providing resources (e.g. social capital in the neighborhood), which individuals can use to cope with health problems, or limiting the use thereof (e.g. crime). This also suggests that there might be age differentials in the impact of these characteristics, since individuals at different stages of life might need different resources. However, there is a lack of empirical evidence on age differentials in associations between well-being, health, and neighborhood characteristics. OBJECTIVE: This paper studies associations between a wide range of neighborhood characteristics with the health and well-being of residents of the greater Berlin area. In particular, we focus on differences in the effects between younger (aged 20-35) and older (aged 60+) residents. METHODS: We used data from the Berlin Aging Study II (312 younger and 993 older residents of the Berlin metropolitan area in Germany). We used survey data on health and well being, combined these with subjective perceptions of the neighborhood, and geo referenced indicators on the neighborhood, e.g. amenities (public transport, physicians, and hospitals). RESULTS: The results show that access to public transportation is associated with better outcomes on all measures of health and well-being, and social support is associated with higher life satisfaction and better mental health. There are considerable differences between both age groups: while the associations between access to public transport and health and well being are similar for both age groups, neighborhood social capital shows stronger associations for older residents. However, the difference is not always statistically significant. CONCLUSION: Having access to services is associated with better health and well-being regardless of age. Local policy makers should focus on lowering barriers to mobility in order to improve the health and well being of the population. Since the social capital of a neighborhood is associated with better health and well-being among older residents, investments that increase social capital (e.g. community centers) might be warranted in neighborhoods with higher shares of older residents. PMID- 26821250 TI - Controllable in situ photo-assisted chemical deposition of CdSe quantum dots on ZnO/CdS nanorod arrays and its photovoltaic application. AB - Compound semiconductors have been widely applied in the energy field as light harvesting materials, conducting substrates and other functional parts. Nevertheless, to effectively grow them in various forms toward objective applications, limitations have often been met to achieving high growth rate, simplicity of method and controllability of growing processes simultaneously. In this work, we have grown a uniform CdSe layer on ZnO/CdS nanorod arrays by a novel in situ photo-assisted chemical deposition method. The morphology and quality of the as-formed material could be significantly influenced by tuning the optical parameters of the injected light. Due to the effect of injected light on the key reactions during the growth, a modified natural light with removal of the UV and IR components seems to be more suitable than monochromic light. An efficiency of 3.59% was achieved without any additional treatment, significantly higher than the efficiency of 2.88% of the sample by conventional CBD method under similar conditions with growth rate one order of magnitude higher. In general, the result has suggested its potential importance for other compound materials and opto-electronic devices. PMID- 26821248 TI - Morphological and Molecular Phylogenetic Position of Prorocentrum micans sensu stricto and Description of Prorocentrum koreanum sp. nov. from Southern Coastal Waters in Korea and Japan. AB - Prorocentrum micans is an extremely variable dinoflagellate species, with many different local forms reported worldwide. Because of this morphological diversity, it is important to establish whether these various forms belong to P. micans sensu stricto. For this study, P. micans-like specimens were isolated from several localities in the southern coastal waters of Korea and Japan. The morphological characteristics and the molecular signatures of P. micans were re examined. Moreover, a new Prorocentrum species, Prorocentrum koreanum sp. nov. was established through detailed light microscopy and scanning electron microscopy observations. Examination of the periflagellar platelets revealed that P. koreanum sp. nov. differs from P. micans. Furthermore, P. koreanum and P. micans exhibited different distribution patterns of trichocyst pores. Through molecular phylogeny analysis of small subunit (SSU) rRNA, internal transcribed spacer (ITS), and large subunit (LSU) rRNA sequence, we found P. koreanum to be more closely related to P. mexicanum and P. rhathymum than to P. micans. Additionally, ITS2 compensatory base changes also provide strong evidence to support P. koreanum and P. micans being separate species. PMID- 26821251 TI - (-)-beta-hydrastine suppresses the proliferation and invasion of human lung adenocarcinoma cells by inhibiting PAK4 kinase activity. AB - (-)-beta-hydrastine is one of the main active components of the medicinal plant, Hydrastis canadensis, which is used in many dietary supplements intended to enhance the immune system. However, whether (-)-beta-hydrastine affects the tumor signaling pathway remains unexplored. In the present study, we found that (-) beta-hydrastine inhibited the kinase activity of p21-activated kinase 4 (PAK4), which is involved in the regulation of cytoskeletal reorganization, cell proliferation, gene transcription, oncogenic transformation and cell invasion. In the present study, (-)-beta-hydrastine suppressed lung adenocarcinoma cell proliferation by inhibiting expression of cyclin D1/D3 and CDK2/4/6, leading to cell cycle arrest at the G1 phase, in a PAK4 kinase-dependent manner. Moreover, inhibition of PAK4 kinase activity by (-)-beta-hydrastine also promoted the early apoptosis of lung adenocarcinoma cells through the mitochondrial apoptosis pathway. In addition, (-)-beta-hydrastine significantly suppressed the migration and invasion of human lung adenocarcinoma cells in conjunction with concomitant blockage of the PAK4/LIMK1/cofilin, PAK4/SCG10 and PAK4/MMP2 pathways. All of these data indicate that (-)-beta-hydrastine, as a novel PAK4 inhibitor, suppresses the proliferation and invasion of lung adenocarcinoma cells. Taken together, these results provide novel insight into the development of a PAK4 kinase inhibitor and a potential therapeutic strategy for lung cancer. PMID- 26821253 TI - Longitudinal assessment of local and global functional connectivity following sports-related concussion. AB - Growing evidence suggests that sports-related concussions (SRC) may lead to acute changes in intrinsic functional connectivity, although most studies to date have been cross-sectional in nature with relatively modest sample sizes. We longitudinally assessed changes in local and global resting state functional connectivity using metrics that do not require a priori seed or network selection (regional homogeneity; ReHo and global brain connectivity; GBC, respectively). A large sample of collegiate athletes (N = 43) was assessed approximately one day (1.74 days post-injury, N = 34), one week (8.44 days, N = 34), and one month post concussion (32.47 days, N = 30). Healthy contact sport-athletes served as controls (N = 51). Concussed athletes showed improvement in mood symptoms at each time point (p's < 0.05), but had significantly higher mood scores than healthy athletes at every time point (p's < 0.05). In contrast, self-reported symptoms and cognitive deficits improved over time following concussion (p's < 0.001), returning to healthy levels by one week post-concussion. ReHo in sensorimotor, visual, and temporal cortices increased over time post-concussion, and was greatest at one month post-injury. Conversely, ReHo in the frontal cortex decreased over time following SRC, with the greatest decrease evident at one month post-concussion. Differences in ReHo relative to healthy athletes were primarily observed at one month post-concussion rather than the more acute time points. Contrary to our hypothesis, no significant cross-sectional or longitudinal differences in GBC were observed. These results are suggestive of a delayed onset of local connectivity changes following SRC. PMID- 26821254 TI - Maternal risks and predictor factors for the termination of pregnancy in fetuses with severe congenital anomaly: experience from a single reference center in Brazil. AB - OBJECTIVE: To assess the maternal complications in pregnant women with fetuses with several congenital anomaly as well as the predictor variables for the termination of pregnancy. METHODS: We performed a retrospective cohort study with 94 medical records of pregnant women with fetal infeasibility confirmed in the postnatal period by clinical, radiological or anatomopathological exams. To compare the categorical variables regarding the termination and nontermination of pregnancy, we used analysis of variance (ANOVA) and the Mann-Whitney U-test. To assess the variables that were more associated with the judicial request for the termination of pregnancy, we used logistic regression. RESULTS: The termination of pregnancy was performed in 41 (43.6%) and nontermination of pregnancy in 53 (56.4%) pregnant women. Pregnant women who did not terminate the pregnancy had more complications in the gestational period (p < 0.0001) and in the postpartum period (p = 0.0088). After multiple logistic regressions, the following variables influenced the decision to terminate the pregnancy: type of congenital anomaly (OR: 18.59; 95%CI: 1.96; 175.87) and living children (OR: 0.45; 95%CI: 0.25; 0.80). CONCLUSION: Most of the pregnant women with fetal infeasibility opted for nontermination of pregnancy and these patients had more obstetrical complications. The type of congenital anomaly and living children were the factors most associated with the choice for the termination of pregnancy. PMID- 26821252 TI - Simulating Serial-Target Antibacterial Drug Synergies Using Flux Balance Analysis. AB - Flux balance analysis (FBA) is an increasingly useful approach for modeling the behavior of metabolic systems. However, standard FBA modeling of genetic knockouts cannot predict drug combination synergies observed between serial metabolic targets, even though such synergies give rise to some of the most widely used antibiotic treatments. Here we extend FBA modeling to simulate responses to chemical inhibitors at varying concentrations, by diverting enzymatic flux to a waste reaction. This flux diversion yields very similar qualitative predictions to prior methods for single target activity. However, we find very different predictions for combinations, where flux diversion, which mimics the kinetics of competitive metabolic inhibitors, can explain serial target synergies between metabolic enzyme inhibitors that we confirmed in Escherichia coli cultures. FBA flux diversion opens the possibility for more accurate genome-scale predictions of drug synergies, which can be used to suggest treatments for infections and other diseases. PMID- 26821256 TI - Pretreatment of Sugar Beet Pulp with Dilute Sulfurous Acid is Effective for Multipurpose Usage of Carbohydrates. AB - Sulfurous acid was used for pretreatment of sugar beet pulp (SBP) in order to achieve high efficiency of both extraction of carbohydrates and subsequent enzymatic hydrolysis of the remaining solids. The main advantage of sulfurous acid usage as pretreatment agent is the possibility of its regeneration. Application of sulfurous acid as hydrolyzing agent in relatively low concentrations (0.6-1.0 %) during a short period of time (10-20 min) and low solid to liquid ratio (1:3, 1:6) allowed effective extraction of carbohydrates from SBP and provided positive effect on subsequent enzymatic hydrolysis. The highest obtained concentration of reducing substances (RS) in hydrolysates was 8.5 %; up to 33.6 % of all carbohydrates present in SBP could be extracted. The major obtained monosaccharides were arabinose and glucose (9.4 and 7.3 g/l, respectively). Pretreatment of SBP with sulfurous acid increased 4.6 times the yield of glucose during subsequent enzymatic hydrolysis of remaining solids with cellulase cocktail, as compared to the untreated SBP. Total yield of glucose during SBP pretreatment and subsequent enzymatic hydrolysis amounted to 89.4 % of the theoretical yield. The approach can be applied directly to the wet SBP. Hydrolysis of sugar beet pulp with sulfurous acid is recommended for obtaining of individual monosaccharides, as well as nutritional media. PMID- 26821255 TI - Efficacy of Mesenchymal Stromal Cell Therapy for Acute Lung Injury in Preclinical Animal Models: A Systematic Review. AB - The Acute Respiratory Distress Syndrome (ARDS) is a devastating clinical condition that is associated with a 30-40% risk of death, and significant long term morbidity for those who survive. Mesenchymal stromal cells (MSC) have emerged as a potential novel treatment as in pre-clinical models they have been shown to modulate inflammation (a major pathophysiological hallmark of ARDS) while enhancing bacterial clearance and reducing organ injury and death. A systematic search of MEDLINE, EMBASE, BIOSIS and Web of Science was performed to identify pre-clinical studies that examined the efficacy MSCs as compared to diseased controls for the treatment of Acute Lung Injury (ALI) (the pre-clinical correlate of human ARDS) on mortality, a clinically relevant outcome. We assessed study quality and pooled results using random effect meta-analysis. A total of 54 publications met our inclusion criteria of which 17 (21 experiments) reported mortality and were included in the meta-analysis. Treatment with MSCs, as compared to controls, significantly decreased the overall odds of death in animals with ALI (Odds Ratio 0.24, 95% Confidence Interval 0.18-0.34, I2 8%). Efficacy was maintained across different types of animal models and means of ALI induction; MSC origin, source, route of administration and preparation; and the clinical relevance of the model (timing of MSC administration, administration of fluids and or antibiotics). Reporting of standard MSC characterization for experiments that used human MSCs and risks of bias was generally poor, and although not statistically significant, a funnel plot analysis for overall mortality suggested the presence of publication bias. The results from our meta analysis support that MSCs substantially reduce the odds of death in animal models of ALI but important reporting elements were sub optimal and limit the strength of our conclusions. PMID- 26821257 TI - The Rapid and Sensitive Quantitative Determination of Galactose by Combined Enzymatic and Colorimetric Method: Application in Neonatal Screening. AB - The quantitative measurement of galactose in blood is essential for the early diagnosis, treatment, and dietary monitoring of galactosemia patients. In this communication, we aimed to develop a rapid, sensitive, and cost-effective combined method for galactose determination in dry blood spots. This procedure was based on the combination of enzymatic reactions of galactose dehydrogenase (GalDH), dihydrolipoyl dehydrogenase (DLD), and alkaline phosphates with a colorimetric system. The incubation time and the concentration of enzymes used in new method were also optimized. The analytical performance was studied by the precision, recovery, linearity, and sensitivity parameters. Statistical analysis was applied to method comparison experiment. The regression equation and correlation coefficient (R (2)) were Y = 0.0085x + 0.032 and R (2) = 0.998, respectively. This assay exhibited a recovery in the range of 91.7-114.3 % and had the limit detection of 0.5 mg/dl for galactose. The between-run coefficient of variation (CV) was between 2.6 and 11.1 %. The within-run CV was between 4.9 and 9.2 %. Our results indicated that the new and reference methods were in agreement because no significant biases exist between them. Briefly, a quick and reliable combined enzymatic and colorimetric assay was presented for application in newborn mass screening and monitoring of galactosemia patients. PMID- 26821258 TI - Characterization and Soluble Expression of D-Hydantoinase from Pseudomonas fluorescens for the Synthesis of D-Amino Acids. AB - An active D-hydantoinase from Pseudomonas fluorescens was heterogeneously overexpressed in Escherichia coli BL21(DE3) and designated as D-PfHYD. Sequence and consensus analysis suggests that D-PfHYD belongs to the dihydropyrimidinase/hydantoinase family and possesses catalytic residues for metal ion and hydantoin binding. D-PfHYD was purified to homogeneity by nickel affinity chromatography for characterization. D-PfHYD is a homotetramer with molecular weight of 215 kDa and specific activity of 20.9 U mg(-1). D-PfHYD showed the highest activity at pH 9.0 and 60 degrees C. Metal ions such as Mn(2+), Fe(2+), and Fe(3+) could activate D-PfHYD with 20 % improvement. Substrate specificity analysis revealed that purified D-PfHYD preferred aliphatic to aromatic 5'-monosubstituted hydantoins. Among various strategies tested, chaperone GroES-GroEL was efficient in improving the soluble expression of D PfHYD. Employing 1.0 g L(-1) recombinant E. coli BL21(DE3)-pET28-hyd/pGRO7 dry cells, 100 mM isobutyl hydantoin was converted into D-isoleucine with 98.7 % enantiomeric excess (ee), isolation yield of 78.3 %, and substrate to biocatalyst ratio of 15.6. Our results suggest that recombinant D-PfHYD could be potentially applied in the synthesis of D-amino acids. PMID- 26821259 TI - From barcodes to genomes: extending the concept of DNA barcoding. AB - DNA barcoding has had a major impact on biodiversity science. The elegant simplicity of establishing massive scale databases for a few barcode loci is continuing to change our understanding of species diversity patterns, and continues to enhance human abilities to distinguish among species. Capitalizing on the developments of next generation sequencing technologies and decreasing costs of genome sequencing, there is now the opportunity for the DNA barcoding concept to be extended to new kinds of genomic data. We illustrate the benefits and capacity to do this, and also note the constraints and barriers to overcome before it is truly scalable. We advocate a twin track approach: (i) continuation and acceleration of global efforts to build the DNA barcode reference library of life on earth using standard DNA barcodes and (ii) active development and application of extended DNA barcodes using genome skimming to augment the standard barcoding approach. PMID- 26821260 TI - Experiences of older adults in a group physiotherapy program at a rehabilitation hospital: A qualitative study. AB - Physiotherapy delivered in a group setting has been shown to be effective in a variety of populations. However, little is known about the attitudes of older adults toward participating in group physiotherapy. The objectives of this study were to explore older inpatients' perceptions and experiences of group physiotherapy using qualitative methods. Twelve hospitalized adults aged >=65 years who were involved in a larger randomized controlled trial undertook individual semistructured interviews regarding their experiences in group physiotherapy. Interviews were transcribed verbatim, and line by line, iterative thematic analysis was undertaken. Descriptive codes were developed, compared, and grouped together to create themes. Analysis revealed 6 major themes and 10 subthemes. All participants reported feeling happy to attend group sessions, a satisfactory alternative to individual physiotherapy. Participants described physical benefits that increased their motivation, and comparisons with their peers either motivated them or made them feel gratitude for their own health. Perceived attentiveness of group instructors contributed to participants reporting that treatment was individualized and similar to individual physiotherapy. Motivation and camaraderie with peers contributed to their enjoyment of group physiotherapy. Hospitalized older adults enjoyed exercising with their peers and valued the physical and social benefits of group physiotherapy. Journal of Hospital Medicine 2016;11:358-362. (c) 2016 Society of Hospital Medicine. PMID- 26821261 TI - Persistent halogenated compounds in fish from rivers in the Pearl River Delta, South China: Geographical pattern and implications for anthropogenic effects on the environment. AB - Three fish species, mud carp (Cirrhinus molitorella), tilapia (Tilapia nilotica), and plecostomus (Hypostomus plecostomus), from rivers in the Pearl River Delta (PRD) were analyzed for dichlorodiphenyltrichloroethane and its metabolites (DDTs), hexachlorocyclohexanes (HCHs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), decabromodiphenyl ethane (DBDPE), and Dechlorane Plus (DP). The concentrations of DDTs, HCHs, PCBs, PBDEs, DBDPE, and DP ranged from 380-57,000, 5.5-100, 30-4200, 6.9-690, 0.29-460, and 0.09-20ng/g lipid weight, respectively. Congener profiles or chemical compositions of PBDEs, DPs, DDTs, and HCHs in plecostomus differed significantly from those in the other two fish species, which can be ascribed to species-specific metabolism. DDTs derived from historical residue and land erosion remained the predominant pollutants in the PRD, while industrial and urban activities resulted in elevated levels of PCBs and PBDEs in the metropolitan area. E-waste recycling activities have greatly impacted on the adjacent aquatic environment, and the potential point source for DBDPE was also revealed. PMID- 26821262 TI - Association of early life exposure to bisphenol A with obesity and cardiometabolic traits in childhood. AB - BACKGROUND: Bisphenol A (BPA) is a chemical used extensively worldwide in the manufacture of plastic polymers. The environmental obesogen hypothesis suggests that early life exposure to endocrine disrupting chemicals such as BPA may increase the risk for wt gain later in childhood but few prospective epidemiological studies have investigated this relationship. OBJECTIVES: We examined the association of early life BPA exposure with offspring obesity and cardiometabolic risk factors in 500 mother-child pairs from the RHEA pregnancy cohort in Crete, Greece. METHODS: BPA concentrations were measured in spot urine samples collected at the 1st trimester of pregnancy) and from children at 2.5 and 4 years of age. We measured birth wt, body mass index (BMI) from 6 months to 4 years of age, waist circumference, skinfold thickness, blood pressure, serum lipids, C-reactive protein, and adipokines at 4 years of age. BMI growth trajectories from birth to 4 years were estimated by mixed effects models with fractional polynomials of age. Adjusted associations were obtained via multivariable regression analyses. RESULTS: The prevalence of overweight/obesity was 9% at 2, 13% at 3% and 17% at 4 years of age. Geometric mean BPA concentrations were 1.2MUg/g creatinine+/-7.9 in 1st trimester, 5.1MUg/g+/-13.3 in 2.5 years and 1.9MUg/g+/-4.9 in 4 years. After confounder adjustment, each 10 fold increase in BPA at 4 years was associated with a higher BMI z-score (adj. beta=0.2; 95% CI: 0.01, 0.4), waist circumference (adj. beta=1.2; 95% CI: 0.1, 2.2) and sum of skinfold thickness (adj. beta=3.7mm; 95% CI: 0.7, 6.7) at 4 years. Prenatal BPA was negatively associated with BMI and adiposity measures in girls and positively in boys. We found no associations of early life exposure to BPA with other offspring cardiometabolic risk factors. CONCLUSIONS: Prenatal BPA exposure was not consistently associated with offspring growth and adiposity measures but higher early childhood BPA was associated with excess child adiposity. PMID- 26821263 TI - Hyaluronan-positive plasma membrane protrusions exist on mesothelial cells in vivo. AB - Previous observations of our research group showed that HAS2 and HAS3 overexpression in cultured cells induces the formation of long and numerous microvillus-like cell protrusions, which are present also in cultured cell types with naturally high hyaluronan secretion and the cell protrusions resemble those found in mesothelial cells. The aim of this study was to investigate whether these hyaluronan secreting, actin-dependent protrusions exist also in vivo. It was found that rat mesothelium in vivo is positive for hyaluronan and Has1-3. Also microvilli in rat mesothelium and live primary cultures of mesothelial cells were found to be hyaluronan positive, and the cells expressed all Has isoforms. Furthermore, ultrastructure of the cell protrusions in rat mesothelium was similar to that induced by overexpression of HAS2 and HAS3, and the number and orientation of actin filaments supporting the cell protrusions was identical. The results of this study show that HA-positive protrusions exist in vivo and support the idea that hyaluronan secretion from plasma membrane protrusions is a general process. This mechanism is potentially crucial for the normal function and maintenance of tissues and body fluids and may be utilized in many therapeutic applications. PMID- 26821264 TI - Fluctuating Nonlinear Spring Model of Mechanical Deformation of Biological Particles. AB - The mechanical properties of virus capsids correlate with local conformational dynamics in the capsid structure. They also reflect the required stability needed to withstand high internal pressures generated upon genome loading and contribute to the success of important events in viral infectivity, such as capsid maturation, genome uncoating and receptor binding. The mechanical properties of biological nanoparticles are often determined from monitoring their dynamic deformations in Atomic Force Microscopy nanoindentation experiments; but a comprehensive theory describing the full range of observed deformation behaviors has not previously been described. We present a new theory for modeling dynamic deformations of biological nanoparticles, which considers the non-linear Hertzian deformation, resulting from an indenter-particle physical contact, and the bending of curved elements (beams) modeling the particle structure. The beams' deformation beyond the critical point triggers a dynamic transition of the particle to the collapsed state. This extreme event is accompanied by a catastrophic force drop as observed in the experimental or simulated force (F) deformation (X) spectra. The theory interprets fine features of the spectra, including the nonlinear components of the FX-curves, in terms of the Young's moduli for Hertzian and bending deformations, and the structural damage dependent beams' survival probability, in terms of the maximum strength and the cooperativity parameter. The theory is exemplified by successfully describing the deformation dynamics of natural nanoparticles through comparing theoretical curves with experimental force-deformation spectra for several virus particles. This approach provides a comprehensive description of the dynamic structural transitions in biological and artificial nanoparticles, which is essential for their optimal use in nanotechnology and nanomedicine applications. PMID- 26821265 TI - Site-Selective Passivation of Defects in NiO Solar Photocathodes by Targeted Atomic Deposition. AB - For nanomaterials, surface chemistry can dictate fundamental material properties, including charge-carrier lifetimes, doping levels, and electrical mobilities. In devices, surface defects are usually the key limiting factor for performance, particularly in solar-energy applications. Here, we develop a strategy to uniformly and selectively passivate defect sites in semiconductor nanomaterials using a vapor-phase process termed targeted atomic deposition (TAD). Because defects often consist of atomic vacancies and dangling bonds with heightened reactivity, we observe-for the widely used p-type cathode nickel oxide-that a volatile precursor such as trimethylaluminum can undergo a kinetically limited selective reaction with these sites. The TAD process eliminates all measurable defects in NiO, leading to a nearly 3-fold improvement in the performance of dye sensitized solar cells. Our results suggest that TAD could be implemented with a range of vapor-phase precursors and be developed into a general strategy to passivate defects in zero-, one-, and two-dimensional nanomaterials. PMID- 26821266 TI - Cross-Cultural Adaptation and Validation of the Dutch Version of the Hip and Groin Outcome Score (HAGOS-NL). AB - BACKGROUND: Valid and reliable questionnaires to assess hip and groin pain are lacking. The Hip and Groin Outcome Score (HAGOS) is a valid and reliable self reported measure to assess symptoms, activity limitations, participation restrictions and quality of life of persons with hip and/or groin complaints. The purpose of this study was to translate and cross-culturally adapt the HAGOS into Dutch (HAGOS-NL), and to evaluate its internal consistency, validity and reliability. METHODS: Translation and cross-cultural adaption of the Dutch version of the HAGOS (HAGOS-NL) was performed according to international guidelines. The study population consisted of 178 adult patients who had undergone groin hernia repair surgery in the previous year. All respondents filled in the HAGOS-NL, the SF-36, and the SMFA-NL for determining construct validity of the HAGOS-NL. To determine reliability, 81 respondents filled in the HAGOS-NL after a time interval of two weeks. RESULTS: Factor analysis confirmed the original six-factor solution of the HAGOS. Internal consistency was good for all the subscales of the HAGOS-NL. High correlations were observed between the HAGOS-NL and the SF-36 and SMFA-NL, indicating good construct validity. The HAGOS NL showed high reliability, except for the subscale Participation in Physical Activities which was moderate. CONCLUSIONS: The HAGOS was successfully translated and cross-culturally adapted from English into Dutch (HAGOS-NL). This study shows that the HAGOS-NL is a valid and reliable instrument for the assessment of functional status and health-related quality of life in patients with groin complaints. PMID- 26821267 TI - Timing of intervention in high-risk non-ST-elevation acute coronary syndromes in PCI versus non-PCI centres : Sub-group analysis of the ELISA-3 trial. AB - AIMS: To compare the effect of timing of intervention in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) in percutaneous coronary intervention (PCI) versus non-PCI centres. METHODS AND RESULTS: A post-hoc sub analysis was performed of the ELISA III trial, a randomised multicentre trial investigating outcome of early (< 12 h) versus late (> 48 h) angiography and revascularisation in 542 patients with high-risk NSTE-ACS. 90 patients were randomised in non-PCI centres and tended to benefit more from an early invasive strategy than patients included in the PCI centre (relative risk 0.23 vs. 0.85 [p for interaction = 0.089] for incidence of the combined primary endpoint of death, reinfarction and recurrent ischaemia after 30 days of follow-up). This was largely driven by reduction in recurrent ischaemia. In non-PCI centres, patients randomised to the late group had a 4 and 7 day longer period until PCI or coronary artery bypass grafting, respectively. This difference was less pronounced in the PCI centre. CONCLUSIONS: This post-hoc analysis from the ELISA 3 trial suggests that NSTE-ACS patients initially hospitalised in non-PCI centres show the largest benefit from early angiography and revascularisation, associated with a shorter waiting time to revascularisation. Improved patient logistics and transfer between non-PCI and PCI centres might therefore result in better clinical outcome. PMID- 26821269 TI - The role of ultrasound in graduate anatomy education: Current state of integration in the United States and faculty perceptions. AB - Ultrasound (US) is increasingly taught in medical schools, where it has been shown to be a valuable adjunct to anatomy training. To determine the extent of US training in nonmedical anatomy programs, and evaluate anatomists' perceptions on the role of US in anatomy education, an online survey was distributed to faculty in anatomy Master's and Doctoral programs. Survey results sampled 71% of anatomy graduate degree programs nationally. Of the faculty surveyed, 65% report little to no experience with US. Thirty-six percent of programs surveyed incorporate exposure to US, while only 15% provide hands-on US training. Opportunities for anatomy trainees to teach with US were found in 12% of programs. Likert responses indicated that anatomists hold overwhelmingly positive views on the contributions of US to anatomy education: 91% agreed US reinforces anatomical concepts (average 4.33 +/- 0.68), 95% agreed it reinforces clinical correlates (average 4.43 +/- 0.65). Anatomists hold moderately positive views on the value of US to the future careers of anatomy graduates: 69% agreed US increases competitiveness on the job market (average 3.91 +/- 0.90), 85% agreed US is a useful skill for a medical school teaching career (average 4.24 +/- 0.75), and 41% agreed that US should be required for a medical education career (average 3.34 +/- 1.09). With continued improvements in technology and the widespread adoption of US into diverse areas of clinical practice, medical education is on the cusp of a paradigm shift with regards to US. Anatomists must decide whether US is an essential skills for the modern anatomist. Anat Sci Educ 9: 453-467. (c) 2016 American Association of Anatomists. PMID- 26821268 TI - Effect of glutamate on lysosomal membrane permeabilization in primary cultured cortical neurons. AB - Glutamate is the principal neurotransmitter in the central nervous system. Glutamate-mediated excitotoxicity is the predominant cause of cerebral damage. Recent studies have shown that lysosomal membrane permeabilization (LMP) is involved in ischemia-associated neuronal death in non-human primates. This study was designed to investigate the effect of glutamate on lysosomal stability in primary cultured cortical neurons. Glutamate treatment for 30 min induced the permeabilization of lysosomal membranes as assessed by acridine orange redistribution and immunofluorescence of cathepsin B in the cytoplasm. Inhibition of glutamate excitotoxicity by the NMDA receptor antagonist MK-801 and the calcium chelator ethylene glycol-bis (2-aminoethylether)-N, N, N', N'-tetraacetic acid, rescued lysosomes from permeabilization. The role of calpain and reactive oxygen species (ROS) in inducing LMP was also investigated. Ca2+ overload following glutamate treatment induced the activation of calpain and the production of ROS, which are two major contributors to neuronal death. It has been reported that lysosomal-associated membrane protein 2 (LAMP2) and heat shock protein (HSP)70 are two calpain substrates that promote LMP in cancer cells; however, it was found that calpains were activated by glutamate, but only LAMP2 was subsequently degraded. Furthermore, LMP was not alleviated by treatment with the calpain inhibitors calpeptin and SJA6017, which blocked the cleavage of the calpain substrate alpha-fodrin. It was demonstrated that LMP was significantly alleviated by treatment with the antioxidant N-Acetyl-L-cysteine, indicating that LMP involvement in early glutamate excitotoxicity may be mediated partly by ROS rather than calpain activation. Overall, these data shed light on the role of ROS mediated LMP in early glutamate excitotoxicity. PMID- 26821270 TI - Evaluation of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry in Identification of Nontuberculous Mycobacteria. AB - BACKGROUND/AIMS: Species-level identification of nontuberculous mycobacteria (NTM) is important in making decisions about the necessity and choice of antimicrobial treatment. The reason is predictable clinical significance and the susceptibility profile of specific NTM species. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is recognized as a diagnostic tool for routine identification of bacteria and yeasts in the clinical laboratory based on protein fingerprint analysis. The aim of the study was to evaluate MALDI-TOF MS in the identification of NTM. METHODS: A total of 25 NTM isolates from liquid cultures were identified with both polymerase chain reaction (PCR)-based hybridization assay and MALDI-TOF MS at the University Hospital Center Zagreb. RESULTS: PCR-based hybridization assay identified 96% (24/25) and MALDI-TOF MS 80% (20/25) of tested NTM isolates. Five isolates with no reliable MALDI-TOF MS identification belonged to the Mycobacterium avium intracellulare complex. Seventy percent (14/20) of NTM isolates successfully identified with MALDI-TOF MS had a score higher than 2.0, indicating reliable species identification. CONCLUSION: MALDI-TOF MS is a promising tool for the identification of NTM. With a further improvement of the protein extraction protocol, especially regarding the M. avium-intracellulare complex, MALDI-TOF MS could be an additional standard method for identification of NTM. PMID- 26821271 TI - Antidepressant Prescription Claims Among Reproductive-Aged Women With Private Employer-Sponsored Insurance - United States 2008-2013. AB - Antidepressant medication use during pregnancy has been increasing in the United States (1). Many women require antidepressants on an ongoing basis, and a clear consensus on the safest medication options for both the mother and her fetus does not exist (2). Given that half of all U.S. pregnancies are unplanned (3), antidepressant use will occur during the first weeks of pregnancy, a critical period for fetal development. To understand trends among women of reproductive age, CDC used Truven Health's MarketScan Commercial Claims and Encounters data* to estimate the number of antidepressant prescriptions filled by women aged 15-44 years with private employer-sponsored insurance. During 2008-2013, an average of 15.4% of women aged 15-44 years filled at least one prescription for an antidepressant in a single year. The most frequently filled antidepressants included sertraline, bupropion, and citalopram. Prescribing of antidepressants is common, and research on antidepressant safety during pregnancy needs to be accelerated to provide evidence-based information to health care providers and women about the potential risks for antidepressant exposure before and during pregnancy and between pregnancies. PMID- 26821272 TI - Drug-Eluting Stent Design is a Determinant of Drug Concentration at the Endothelial Cell Surface. AB - Although drug-eluting stents (DES) have greatly reduced arterial restenosis, there are persistent concerns about stent thrombosis. DES thrombosis is attributable to retarded vascular re-endothelialization due to both stent-induced flow disturbance and the inhibition by the eluted drug of endothelial cell proliferation and migration. The present computational study aims to determine the effect of DES design on both stent-induced flow disturbance and the concentration of eluted drug at the arterial luminal surface. To this end, we consider three closed-cell stent designs that resemble certain commercial stents as well as three "idealized" stents that provide insight into the impact of specific characteristics of stent design. To objectively compare the different stents, we introduce the Stent Penalty Index (SPI), a dimensionless quantity whose value increases with both the extent of flow disturbance and luminal drug concentration. Our results show that among the three closed-cell designs studied, wide cell designs lead to lower SPI and are thus expected to have a less adverse effect on vascular re-endothelialization. For the idealized stent designs, a spiral stent provides favorable SPI values, whereas an intertwined ring stent leads to an elevated SPI. The present findings shed light onto the effect of stent design on the concentration of the eluted drug at the arterial luminal surface, an important consideration in the assessment of DES performance. PMID- 26821273 TI - Addressing access barriers to services for mothers at risk for perinatal mood disorders: A social work perspective. AB - This article identifies variables at the micro/individual, mezzo/partner/spouse and family, and macro/health care-system levels that inhibit mothers at risk for perinatal mood disorders from accessing health and mental health care services. Specific recommendations are made for conducting thorough biopsychosocial assessments that address the mothers' micro-, mezzo-, and macro-level contexts. Finally, the authors provide suggestions for how to intervene at the various levels to remove access barriers for mothers living with perinatal mood disorders as well as their families. PMID- 26821274 TI - Ionothermal Synthesis of MnAPO-SOD Molecular Sieve without the Aid of Organic Structure-Directing Agents. AB - An SOD-type metalloaluminophosphate molecular sieve (denoted as SOD-Mn) was ionothermally synthesized by introducing manganese(II) cations into the reaction mixture via MnO-acid or MnO2-reductant reactions. Composition and structure analyses results show that two kinds of manganese(II) cations exist in the SOD-Mn structure. Part of the manganese(II) cations isomorphously substitute the framework aluminum(III) with a substitution degree of ~30%. The rest of the manganese(II) cations occupy a fraction of the sod cages in their hydrated forms. A comprehensive investigation of the synthesis parameters, crystal sizes, and crystallization kinetics indicates that the in situ released hydrated manganese(II) cations direct the formation of SOD-Mn. Such structure-directing effect may be inhibited by both the fluorination of manganese(II) cations and the water accumulation during crystallization. In the fluoride anion-containing reaction mixture with a low ionic liquid content, the crystallization process is strongly suppressed, and large SOD-Mn single crystals of over 200 MUm in size are yielded. SOD-Mn is free from organics and shows improved thermal stability compared with metalloaluminophosphates synthesized by using organic structure directing agents. PMID- 26821275 TI - Quaternary Ammonium Disinfectant Issues Encountered in an Environmental Services Department. AB - We identified several factors affecting the use of quaternary ammonium-based (Quat) disinfectant in our facility. Microfiber wipers, cotton towels, and 1 of 2 types of disposable wipes soaked in a Quat disinfectant revealed significant binding of the disinfectant. Concentrations of Quat delivered by automated disinfectant dispensers varied widely. PMID- 26821276 TI - Evaluation of nefazodone-induced cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes. AB - The recent establishment of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), which express the major cardiac ion channels and recapitulate spontaneous mechanical and electrical activities, may provide a possible solution for the lack of in vitro human-based cardiotoxicity testing models. Cardiotoxicity induced by the antidepressant nefazodone was previously revealed to cause an acquired QT prolongation by hERG channel blockade. To elucidate the cellular mechanisms underlying the cardiotoxicity of nefazodone beyond hERG, its effects on cardiac action potentials (APs) and ion channels were investigated using hiPSC-CMs with whole-cell patch clamp techniques. In a proof of principle study, we examined the effects of cardioactive channel blockers on the electrophysiological profile of hiPSC-CMs in advance of the evaluation of nefazodone. Nefazodone dose-dependently prolonged the AP duration at 90% (APD90) and 50% (APD50) repolarization, reduced the maximum upstroke velocity (dV/dtmax) and induced early after depolarizations. Voltage-clamp studies of hiPSC-CMs revealed that nefazodone inhibited various voltage-gated ion channel currents including IKr, IKs, INa, and ICa. Among them, IKr and INa showed relatively higher sensitivity to nefazodone, consistent with the changes in the AP parameters. In summary, hiPSC-CMs enabled an integrated approach to evaluate the complex interactions of nefazodone with cardiac ion channels. These results suggest that hiPSC-CMs can be an effective model for detecting drug-induced arrhythmogenicity beyond the current standard assay of heterologously expressed hERG K(+) channels. PMID- 26821277 TI - On Singularities and Black Holes in Combination-Driven Models of Technological Innovation Networks. AB - It has been suggested that innovations occur mainly by combination: the more inventions accumulate, the higher the probability that new inventions are obtained from previous designs. Additionally, it has been conjectured that the combinatorial nature of innovations naturally leads to a singularity: at some finite time, the number of innovations should diverge. Although these ideas are certainly appealing, no general models have been yet developed to test the conditions under which combinatorial technology should become explosive. Here we present a generalised model of technological evolution that takes into account two major properties: the number of previous technologies needed to create a novel one and how rapidly technology ages. Two different models of combinatorial growth are considered, involving different forms of ageing. When long-range memory is used and thus old inventions are available for novel innovations, singularities can emerge under some conditions with two phases separated by a critical boundary. If the ageing has a characteristic time scale, it is shown that no singularities will be observed. Instead, a "black hole" of old innovations appears and expands in time, making the rate of invention creation slow down into a linear regime. PMID- 26821278 TI - Prostate MRSI predicts outcome in radical prostatectomy patients. AB - BACKGROUND: New non-invasive methods are needed for sub-stratifying high-risk prostate cancer patients. Magnetic resonance spectroscopic imaging (MRSI) maps metabolites in prostate cancer, providing information on tumor aggressiveness and volume. PURPOSE: To investigate the correlation between MRSI and treatment failure (TF) after radical prostatectomy (RP). METHODS: Two-hundred sixty-two patients who underwent endorectal MRI/MRSI followed by RP at our institution from 2003 to 2007 were studied. MRI stage, number of voxels in the MRSI index lesion (NILV), number of high-grade voxels (NHGV), and number of voxels containing undetectable polyamines (NUPV) were derived. Clinical outcome was followed until August, 2014. Treatment failure was defined as 1) biochemical recurrence (BCR), 2) persistently detectable PSA after RP, or 3) adjuvant therapy initiated in the absence of BCR. MRI/MRSI features and clinical parameters were compared to TF by univariate Cox Proportional Hazards Regression. After backward selection, each MRSI parameter was included in a separate regression model adjusted for NCCN based clinical risk score (CRS), number of biopsy cores positive (NPC), and MRI stage. RESULTS: In univariate analysis, all clinical variables were associated with TF in addition to MRI stage, NILV, NHGV, and NUPV. In multivariate analysis, NILV, NHGV, and NUPV were also significant risk factors for TF (p=0.016, p=0.002, p=0.006, respectively). The association between the number of tumor voxels with undetectable polyamines and the probability of treatment failure has not been previously reported. The number of MRSI cancer voxels correlated with extracapsular extension (ECE) (p<0.0001). CONCLUSIONS: MRSI was associated with post-radical prostatectomy treatment failure in models adjusted for the number of positive biopsy cores and clinical risk score. This is the first report that in radical prostatectomy patients MRSI has an association with treatment failure independent of the number of positive biopsy cores. MRSI may help the clinician determine whether patients with high risk disease who undergo RP are candidates for specialized additional treatment. PMID- 26821279 TI - Triptolide decreases expression of latency-associated nuclear antigen 1 and reduces viral titers in Kaposi's sarcoma-associated and herpesvirus-related primary effusion lymphoma cells. AB - Kaposi's sarcoma-associated herpesvirus (KSHV) can establish a life-long persistence in the host after primary infection and is associated with certain malignancies, which are resistant to conventional chemotherapeutic agents with a poor prognosis. Latency-associated nuclear antigen 1 (LANA1) encoded by KSHV is essential for segregation, replication and maintenance of viral genome. In addition, LANA1 upregulates the transcriptional activity of signal transducer and activator of transcription 3 (STAT3), which plays an important role in promoting survival of KSHV-associated primary effusion lymphoma (PEL) cells. Furthermore, LANA1 mediates transcriptional modulation of KSHV and host genome in host cells. In the present study, the antitumor effect of triptolide was assessed. CCK-8 assays were performed to demonstrate that the proliferations of PEL cells were efficiently inhibited by triptolide in a dose- and time-dependent manner. Flow cytometric results indicated that triptolide induced cell cycle arrest and apoptosis. Western blot results suggested that triptolide downregulated LANA1 expression and reduced half-life of LANA1 in the KSHV-infected malignant cells. Viral titer experiments indicated that triptolide treatment impaired the number of viral DNA copies and the production of virions in BCBL-1 cells. Triptolide also suppressed STAT3 activity and inhibited secretion of IL-6 in PEL cells. In a mouse xenograft model of primary effusion lymphoma by BCBL-1 cells, triptolide treatment significantly inhibited ascites formation and diffused organ infiltration. These results indicate that triptolide impairs the expression of LANA1 and shows antitumor activity against PEL in vitro and in vivo. Triptolide may be a potential agent for treatment of PEL. PMID- 26821280 TI - Insulin Glargine 300 U/mL: A Review in Diabetes Mellitus. AB - Insulin glargine 300 U/mL (Toujeo((r))) is a long-acting basal insulin analogue approved for the treatment of diabetes mellitus. Insulin glargine 300 U/mL has a more stable and prolonged pharmacokinetic/pharmacodynamic profile than insulin glargine 100 U/mL (Lantus((r))), with a duration of glucose-lowering activity exceeding 24 h. In several 6-month phase III trials, insulin glargine 300 U/mL achieved comparable glycaemic control to that seen with insulin glargine 100 U/mL in patients with type 1 or type 2 diabetes, albeit with consistently higher daily basal insulin requirements. These improvements in glycaemic control were maintained during longer-term (12 months) treatment. Insulin glargine 300 U/mL was generally associated with a lower risk of nocturnal hypoglycaemia than insulin glargine 100 U/mL in insulin-experienced patients with type 2 diabetes, while the risk of nocturnal hypoglycaemia did not significantly differ between treatment groups in insulin-naive patients with type 2 diabetes or in patients with type 1 diabetes. To conclude, once-daily subcutaneous insulin glargine 300 U/mL is an effective and generally well tolerated basal insulin therapy option for patients with type 1 or type 2 diabetes. PMID- 26821281 TI - Quantification of 18FDG in the Normal Colon-A First Step in Investigating Whether Its Presence Is a Marker of a Physiological Process. AB - The visibility of the colon in positron emission tomography (PET) scans of patients without gastrointestinal disease indicating the presence of 18F Fluorodeoxyglucose (18FDG) is well recognised, but unquantified and unexplained. In this paper a qualitative scoring system was applied to PET scans from 30 randomly selected patients without gastrointestinal disease to detect the presence of 18FDG in 4 different sections of the colon and then both the total pixel value and the pixel value per unit length of each section of the colon were determined to quantify the amount of 18FDG from a randomly selected subset of 10 of these patients. Analysis of the qualitative scores using a non-parametric ANOVA showed that all sections of the colon contained 18FDG but there were differences in the amount of 18FDG present between sections (p<0.05). Wilcoxon matched-pair signed-rank tests between pairs of segments showed statistically significant differences between all pairs (p<0.05) with the exception of the caecum and ascending colon and the descending colon. The same non-parametric statistical analysis of the quantitative measures showed no difference in the total amount of 18FDG between sections (p>0.05), but a difference in the amount/unit length between sections (p<0.01) with only the caecum and ascending colon and the descending colon having a statistically significant difference (p<0.05). These results are consistent since the eye is drawn to focal localisation of the 18FDG when qualitatively scoring the scans. The presence of 18FDG in the colon is counterintuitive since it must be passing from the blood to the lumen through the colonic wall. There is no active mechanism to achieve this and therefore we hypothesise that the transport is a passive process driven by the concentration gradient of 18FDG across the colonic wall. This hypothesis is consistent with the results obtained from the qualitative and quantitative measures analysed. PMID- 26821282 TI - Genetic variations in GPSM3 associated with protection from rheumatoid arthritis affect its transcript abundance. AB - G protein signaling modulator 3 (GPSM3) is a regulator of G protein-coupled receptor signaling, with expression restricted to leukocytes and lymphoid organs. Previous genome-wide association studies have highlighted single-nucleotide polymorphisms (SNPs; rs204989 and rs204991) in a region upstream of the GPSM3 transcription start site as being inversely correlated to the prevalence of rheumatoid arthritis (RA)-this association is supported by the protection afforded to Gpsm3-deficient mice in models of inflammatory arthritis. Here, we assessed the functional consequences of these polymorphisms. We collected biospecimens from 50 volunteers with RA diagnoses, 50 RA-free volunteers matched to the aforementioned group and 100 unmatched healthy young volunteers. We genotyped these individuals for GPSM3 (rs204989, rs204991), CCL21 (rs2812378) and HLA gene region (rs6457620) polymorphisms, and found no significant differences in minor allele frequencies between the RA and disease-free cohorts. However, we identified that individuals homozygous for SNPs rs204989 and rs204991 had decreased GPSM3 transcript abundance relative to individuals homozygous for the major allele. In vitro promoter activity studies suggest that SNP rs204989 is the primary cause of this decrease in transcript levels. Knockdown of GPSM3 in THP-1 cells, a human monocytic cell line, was found to disrupt ex vivo migration to the chemokine MCP-1. PMID- 26821283 TI - The SLE variant Ala71Thr of BLK severely decreases protein abundance and binding to BANK1 through impairment of the SH3 domain function. AB - The B-lymphocyte kinase (BLK) gene is associated genetically with several human autoimmune diseases including systemic lupus erythematosus. We recently described that the genetic risk is given by two haplotypes: one covering several strongly linked single-nucleotide polymorphisms within the promoter of the gene that correlated with low transcript levels, and a second haplotype that includes a rare nonsynonymous variant (Ala71Thr). Here we show that this variant, located within the BLK SH3 domain, is a major determinant of protein levels. In vitro analyses show that the 71Thr isoform is hyperphosphorylated and promotes kinase activation. As a consequence, BLK is ubiquitinated, its proteasomal degradation enhanced and the average life of the protein is reduced by half. Altogether, these findings suggest that an intrinsic autoregulatory mechanism previously unappreciated in BLK is disrupted by the 71Thr substitution. Because the SH3 domain is also involved in protein interactions, we sought for differences between the two isoforms in trafficking and binding to protein partners. We found that binding of the 71Thr variant to the adaptor protein BANK1 is severely reduced. Our study provides new insights on the intrinsic regulation of BLK activation and highlights the dominant role of its SH3 domain in BANK1 binding. PMID- 26821284 TI - TALEN-mediated enhancer knockout influences TNFAIP3 gene expression and mimics a molecular phenotype associated with systemic lupus erythematosus. AB - Linkage disequilibrium poses a major challenge to the functional characterization of specific disease-associated susceptibility variants. Precision genome-editing technologies have provided new opportunities to address this challenge. As proof of concept, we employed TALEN (transcription activation-like effector nuclease) mediated genome editing to specifically disrupt the TT>A enhancer region to mimic candidate causal variants identified in the systemic lupus erythematosus associated susceptibility gene, tumor necrosis factor-alpha-induced protein 3 (TNFAIP3), in an isogenic HEK293T cell line devoid of other linkage disequilibrium-associated variants. Targeted disruption of the TT>A enhancer impaired its interaction with the TNFAIP3 promoter by long-range DNA looping, thereby reducing TNFAIP3 gene expression. Loss of TNFAIP3 mRNA and its encoded protein, A20, impaired tumor necrosis factor-alpha-induced receptor-mediated downregulation of nuclear factor-kappaB signaling, a hallmark of autoimmunity. Results demonstrate that the TT>A enhancer variants contribute to causality and function independently of other variants to disrupt TNFAIP3 expression. Furthermore, we believe this approach can be implemented to independently examine other candidate casual variants in the future. PMID- 26821285 TI - Swedish children with hereditary angioedema report good overall health and quality of life despite symptoms. AB - AIM: Few studies have been published on children with hereditary angioedema (HAE), an autosomal dominant disease caused by mutations on chromosome 11. This study explored various aspects of the disease in the Swedish paediatric population. METHODS: A retrospective questionnaire was sent to all 36 Swedish children known to have HAE, and a physician carried out follow-up telephone interviews. RESULTS: Most of the questionnaires were completed by the parents of 31 (86%) children with HAE, with or without their input, at a median age of nine years (range 1-17), and the physician also interviewed 29. HAE symptoms were experienced by 23 children, including abdominal attacks (96%), skin swelling (78%) and swelling in the mouth and/or upper airways (52%). Psychological stress was the most common trigger for abdominal attacks and trauma and sports triggered skin swelling. The majority (n = 19) had access to complement-1 esterase inhibitor concentrate at home. Current health and quality of life were generally rated as good, independent of whether the child had experienced HAE symptoms or not. CONCLUSION: Most children with HAE had experienced abdominal attacks and skin swelling, but their overall health and quality of life were generally perceived to be good. PMID- 26821286 TI - A novel compact mass detection platform for the open access (OA) environment in drug discovery and early development. AB - A new 'compact mass detector' co-developed with an instrument manufacturer (Waters Corporation) as an interface for liquid chromatography (LC), specifically Ultra-high performance LC((r)) (UPLC((r)) or UHPLC) analysis was evaluated as a potential new Open Access (OA) LC-MS platform in the Drug Discovery and Early Development space. This new compact mass detector based platform was envisioned to provide increased reliability and speed while exhibiting significant cost, noise, and footprint reductions. The new detector was evaluated in batch mode (typically 1-3 samples per run) to monitor reactions and check purity, as well as in High Throughput Screening (HTS) mode to run 24, 48, and 96 well plates. The latter workflows focused on screening catalysis conditions, process optimization, and library work. The objective of this investigation was to assess the performance, reliability, and flexibility of the compact mass detector in the OA setting for a variety of applications. The compact mass detector results were compared to those obtained by current OA LC-MS systems, and the capabilities and benefits of the compact mass detector in the open access setting for chemists in the drug discovery and development space are demonstrated. PMID- 26821287 TI - Severe, multimodal stress exposure induces PTSD-like characteristics in a mouse model of single prolonged stress. AB - Appropriate animal models of posttraumatic stress disorder (PTSD) are needed because human studies remain limited in their ability to probe the underlying neurobiology of PTSD. Although the single prolonged stress (SPS) model is an established rat model of PTSD, the development of a similarly-validated mouse model emphasizes the benefits and cross-species utility of rodent PTSD models and offers unique methodological advantages to that of the rat. Therefore, the aims of this study were to develop and describe a SPS model for mice and to provide data that support current mechanisms relevant to PTSD. The mouse single prolonged stress (mSPS) paradigm, involves exposing C57Bl/6 mice to a series of severe, multimodal stressors, including 2h restraint, 10 min group forced swim, exposure to soiled rat bedding scent, and exposure to ether until unconsciousness. Following a 7-day undisturbed period, mice were tested for cue-induced fear behavior, effects of paroxetine on cue-induced fear behavior, extinction retention of a previously extinguished fear memory, dexamethasone suppression of corticosterone (CORT) response, dorsal hippocampal glucocorticoid receptor protein and mRNA expression, and prefrontal cortex glutamate levels. Exposure to mSPS enhanced cue-induced fear, which was attenuated by oral paroxetine treatment. mSPS also disrupted extinction retention, enhanced suppression of stress-induced CORT response, increased mRNA expression of dorsal hippocampal glucocorticoid receptors and decreased prefrontal cortex glutamate levels. These data suggest that the mSPS model is a translationally-relevant model for future PTSD research with strong face, construct, and predictive validity. In summary, mSPS models characteristics relevant to PTSD and this severe, multimodal stress modifies fear learning in mice that coincides with changes in the hypothalamo pituitary-adrenal (HPA) axis, brain glucocorticoid systems, and glutamatergic signaling in the prefrontal cortex. PMID- 26821288 TI - Chronic fluoxetine treatment induces anxiolytic responses and altered social behaviors in medaka, Oryzias latipes. AB - Medaka (Oryzias latipes) is a small freshwater teleost that is an emerging model system for neurobehavioral research and toxicological testing. The selective serotonin reuptake inhibitor class of antidepressants such as fluoxetine is one of the widely prescribed drugs, but little is known about the effects of these drugs on medaka behaviors. To assess the behavioral effects of fluoxetine, we chronically administrated fluoxetine to medaka adult fish and analyzed the anxiety-related and social behaviors using five behavioral paradigms (diving, open-field, light-dark transition, mirror-biting, and social interaction) with an automated behavioral testing system. Fish chronically treated with fluoxetine exhibited anxiolytic responses such as an overall increased time spent in the top area in the diving test and an increased time spent in center area in the open field test. Analysis of socially evoked behavior showed that chronic fluoxetine administration decreased the number of mirror biting times in the mirror-biting test and increased latency to first contact in the social interaction test. Additionally, chronic fluoxetine administration reduced the horizontal locomotor activity in the open-field test but not the vertical activity in the diving test. These investigations are mostly consistent with previous reports in the other teleost species and rodent models. These results indicate that behavioral assessment in medaka adult fish will become useful for screening of effects of pharmaceutical and toxicological compounds in animal behaviors. PMID- 26821290 TI - Long-term deficits of the paretic limb follow post-stroke compensatory limb use in C57BL/6 mice. AB - Stroke is a leading cause of long-term disability that most often results in impairment of a single limb, contralateral to the injury (paretic limb). While stroke survivors often receive some type of rehabilitative training, chronic deficits persist. It has been suggested that compensatory use of the nonparetic limb immediately after injury may underlie these long-term consequences. The current study investigated the behavioral effects of early compensatory limb use on behavioral outcome of the paretic limb in a mouse model of stroke. Mice received unilateral stroke after acquiring skilled motor performance on a reaching task. Following injury, mice received either delayed rehabilitation of the paretic limb or compensatory limb training prior to delayed rehabilitative training. After 28 days of focused rehabilitative training of the paretic limb, mice that had previously received compensatory limb training exhibited performance that was similar to their initial deficit after stroke while mice that received delayed rehabilitative training improved to pre-operative performance levels. Our results indicate that even with extensive focused training of the paretic limb, early compensatory limb use has a lasting impact on the behavioral flexibility and ultimate functional outcome of the paretic limb. PMID- 26821289 TI - Activation of corticotropin releasing factor-containing neurons in the rat central amygdala and bed nucleus of the stria terminalis following exposure to two different anxiogenic stressors. AB - Rats exposed to the odor of a predator or to the elevated plus maze (EPM) express unique unconditioned fear behaviors. The extended amygdala has previously been demonstrated to mediate the response to both predator odor and the EPM. We seek to determine if divergent amygdalar microcircuits are associated with the different behavioral responses. The current experiments compared activation of corticotropin-releasing factor (CRF)-containing neuronal populations in the central amygdala and bed nucleus of the stria terminalis (BNST) of rats exposed to either the EPM (5 min) versus home cage controls, or predator (ferret) odor versus butyric acid, or no odor (30 min). Sections of the brains were prepared for dual-labeled immunohistochemistry and counts of c-Fos co-localized with CRF were made in the centrolateral and centromedial amygdala (CLA and CMA) as well as the dorsolateral (dl), dorsomedial (dm), and ventral (v) BNST. Ferret odor exposed rats displayed an increase in duration and a decrease in latency of defensive burying versus control rats. Exposure to both predator stress and EPM induced neuronal activation in the BNST, but not the central amygdala, and similar levels of neuronal activation were seen in both the high and low anxiety groups in the BNST after EPM exposure. Dual-labeled immunohistochemistry showed a significant increase in the percentage of CRF/c-Fos co-localization in the vBNST of ferret odor-exposed rats compared to control and butyric acid-exposed groups as well as EPM-exposed rats compared to home cage controls. In addition, an increase in the percentage of CRF-containing neurons co-localized with c-Fos was observed in the dmBNST after EPM exposure. No changes in co-localization of CRF with c-Fos was observed with these treatments in either the CLA or CMA. These results suggest that predator odor and EPM exposure activates CRF neurons in the BNST to a much greater extent than CRF neurons of the central amygdala, and indicates unconditioned anxiogenic stimuli may activate unique anatomical circuits in the extended amygdala. PMID- 26821291 TI - Learning, memory and long-term potentiation are altered in Nedd4 heterozygous mice. AB - The consolidation of short-term memory into long-term memory involves changing protein level and activity for the synaptic plasticity required for long-term potentiation (LTP). AMPA receptor trafficking is a key determinant of LTP and recently ubiquitination by Nedd4 has been shown to play an important role via direct action on the GluA1 subunit, although the physiological relevance of these findings are yet to be determined. We therefore investigated learning and memory in Nedd4(+/-) mice that have a 50% reduction in levels of Nedd4. These mice showed decreased long-term spatial memory as evidenced by significant increases in the time taken to learn the location of and subsequently find a platform in the Morris water maze. In contrast, there were no significant differences between Nedd4(+/+) and Nedd4(+/-) mice in terms of short-term spatial memory in a Y-maze test. Nedd4(+/-) mice also displayed a significant reduction in post-synaptic LTP measured in hippocampal brain slices. Immunofluorescence of Nedd4 in the hippocampus confirmed its expression in hippocampal neurons of the CA1 region. These findings indicate that reducing Nedd4 protein by 50% significantly impairs LTP and long-term memory thereby demonstrating an important role for Nedd4 in these processes. PMID- 26821292 TI - CaMKIIalpha knockdown decreases anxiety in the open field and low serotonin induced upregulation of GluA1 in the basolateral amygdala. AB - Hyperactivation of the amygdala is implicated in anxiety and mood disorders, but the precise underlying mechanisms are unclear. We previously reported that depletion of serotonin (5-hydroxytryptamine, 5-HT) in the basolateral nucleus of the amygdala (BLA) using the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7 DHT) potentiated learned fear and increased glutamate receptor (Glu) expression in BLA. Here we investigated the hypothesis that CaMKII facilitates anxiety-like behavior and increased Glu/AMPA receptor subunit A1 (GluA1) expression following depletion of 5-HT in the BLA. Infusion of 5,7-DHT into the BLA resulted in anxiety-like behavior in the open field test (OFT) and increased the phosphorylation of CaMKIIalpha (Thr-286) in the BLA. Knockdown of the CaMKIIalpha subunit using adeno-associated virus (AAV)-delivered shRNAi concomitantly attenuated anxiety-like behavior in the OFT and decreased GluA1 expression in the BLA. Our results suggest that the CaMKII signaling plays a key role in low 5-HT induced anxiety and mood disturbances, potentially through regulation of GluA1 expression in the BLA. PMID- 26821294 TI - Expression of Cryptosporidium parvum thioredoxin peroxidase in COS-7 cells confers radioprotection. AB - Cryptosporidium parvum is one of the most radioresistant organisms identified to date. In a previous study, we found that thioredoxin peroxidase (CpTPx) was significantly upregulated in this species following exposure to high dose (10 kGy) of gamma-irradiation. To assess the potential of CpTPx to confer radioprotection in mammalian cells, it was expressed in COS-7 African green monkey kidney cells (CpTPx-COS7). For comparison, the thioredoxin peroxidase of Cryptosporidium muris (CmTPx) was also expressed in these cells (CmTPx-COS7 cells), which has been confirmed to have lesser antioxidant activity than CpTPx in the previous study. Notably, the survival rates of CpTPx-COS7 cells were significantly higher (12-22%) at 72 h after 8 Gy irradiation than CmTPx-COS7 or non-transfected COS-7 (ntCOS-7) counterparts. In addition, CpTPx revealed a 50% of ROS reduction in irradiated CpTPx-COS7 cells, while gamma-H2AX DNA damage marker expression was not significantly changed. Furthermore, the amount of apoptosis only increased to about 120% after 2-8 Gy irradiation compared to 200 300% increase observed in ntCOS-7 cells. CmTPx was shown to have antioxidant and DNA damage protection activities; however, these activities were always lower than those of CpTPx. These results suggest that the potent antioxidant and protective activities of CpTPx are well conserved in this cell-based system and that CpTPx contributed to the radioprotection of mammalian cells through its exceptional antioxidant activity. PMID- 26821293 TI - Binge ethanol withdrawal: Effects on post-withdrawal ethanol intake, glutamate glutamine cycle and monoamine tissue content in P rat model. AB - Alcohol withdrawal syndrome (AWS) is a medical emergency situation which appears after abrupt cessation of ethanol intake. Decreased GABA-A function and increased glutamate function are known to exist in the AWS. However, the involvement of glutamate transporters in the context of AWS requires further investigation. In this study, we used a model of ethanol withdrawal involving abrupt cessation of binge ethanol administration (4 g/kg/gavage three times a day for three days) using male alcohol-preferring (P) rats. After 48 h of withdrawal, P rats were re exposed to voluntary ethanol intake. The amount of ethanol consumed was measured during post-withdrawal phase. In addition, the expression of GLT-1, GLAST and xCT were determined in both medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). We also measured glutamine synthetase (GS) activity, and the tissue content of glutamate, glutamine, dopamine and serotonin in both mPFC and NAc. We found that binge ethanol withdrawal escalated post-withdrawal ethanol intake, which was associated with downregulation of GLT-1 expression in both mPFC and NAc. The expression of GLAST and xCT were unchanged in the ethanol-withdrawal (EW) group compared to control group. Tissue content of glutamate was significantly lower in both mPFC and NAc, whereas tissue content of glutamine was higher in mPFC but unchanged in NAc in the EW group compared to control group. The GS activity was unchanged in both mPFC and NAc. The tissue content of DA was significantly lower in both mPFC and NAc, whereas tissue content of serotonin was unchanged in both mPFC and NAc. These findings provide important information of the critical role of GLT-1 in context of AWS. PMID- 26821295 TI - Protective efficacy of pVAX-RON5p against acute and chronic infections of Toxoplasma gondii in BALB/c mice. AB - Toxoplasma gondii can infect all the warm-blooded animals and humans and causes serious diseases especially in immuno-compromised patients and pregnant women. Rhoptry neck proteins (RONs) play an important role in the formation of moving junction, which mediates the invasion of this parasite. A recombinant plasmid pVAX-RON5p, which can express part of RON5 protein in the eukaryocyte, was generated and used to immune BALB/c mice for evaluating the protective efficacy against the acute and chronic infections of T. gondii. Both humoral and cellular immune responses were evoked in mice by pVAX-RON5p immunization, and a slightly prolonged survival period was detected in the immunized group (7.6 +/- 3.31 days) compared to the blank control (4.9 +/- 0.32 days) after acute T. gondii infection (P < 0.05). For chronic infection of T. gondii, the number of cysts in the brain of pVAX-RON5p-immunized mice decreased 25.8% compared to blank control (P < 0.05). Our data suggested that RON5p DNA vaccine can induce partial protective immunity against acute and chronic T. gondii infections. PMID- 26821296 TI - Design, synthesis and antimalarial screening of some hybrid 4-aminoquinoline triazine derivatives against pf-DHFR-TS. AB - Existing antifolate antimalarial drugs have shown resistance due to the mutations at some amino acid positions of Plasmodium falciparum DHFR-TS. In the present study, to overcome this resistance, a new series of hybrid 4-aminoquinoline triazine derivatives were designed and docked into the active site of Pf-DHFR-TS (PDB i.d. 1J3K) using validated CDOCKER protocol. Binding energy was calculated by applying CHARMm forcefield. Binding energy and the pattern of interaction of the docked compounds were analysed. Fifteen compounds were selected for synthesis based on their binding energy values and docking poses. Synthesized compounds were characterised by FTIR, (1)H NMR, (13)C NMR, mass spectroscopy and were screened for antimalarial activity against 3D7 strain of Plasmodium falciparum. PMID- 26821297 TI - Morphological and molecular characterization of Isospora manorinae n. sp. in a yellow-throated miner (Manorina flavigula wayensis) (Gould, 1840). AB - A new Isospora (Apicomplexa:Eimeriidae) species is described from a single yellow throated miner bird (Manorina flavigula) (subspecies M. f. wayensis) in Western Australia. Sporulated oocysts (n = 32) of this isolate are spherical to subspherical, 22.8 (20.3-23.8) * 18.3 (17.7-18.7) MUm, with a shape index (length/width) of 1.25 (1.2-1.3); and a smooth and bilayered oocyst wall, 1.3 MUm thick (outer layer 0.9 MUm, inner 0.4 MUm). A polar granule is present, but the micropyle and oocyst residuum are absent. The sporocysts are lemon-shaped, 15.5 (14.6-15.8) * 9.5 (9.5-10.2) MUm, with a shape index of 1.6. Stieda and substieda bodies are present, the Stieda body being knob-like and the substieda body being subspherical-shaped. A sporocyst residuum is present and composed of numerous granules of different size scattered among the sporozoites, a spheroid or subspheroid refractile body is present in the sporozoite. Morphologically, the oocysts from this isolate are different from those of all known valid Isospora spp. Molecular analysis was conducted at 3 loci; the 18S and 28S ribosomal RNA and the mitochondrial cytochrome oxidase (COI) gene. At the 18S locus, this new isolate exhibited 99.2% similarity to Isospora gryphoni and three other Isospora spp. Further analysis of a subgroup of 300 bp long 18S sequences (8), including Isospora anthochaerae was conducted. This new isolate grouped in a clade with I. anthochaerae and exhibited 99.3% similarity. At the 28S locus, this new isolate grouped with I. anthochaerae with which it shared 99.1% similarity. At the COI locus, this new isolate exhibited 96.8% similarity to Isospora sp. JCI-2015 from a spectacled warbler (Sylvia conspicillata) in Spain. Further analysis from a subgroup of shorter COI sequences (n = 13) was performed and this new isolate exhibited 99.1% similarity to I. anthochaerae. Based on morphological and molecular data, this isolate is a new species of Isospora, which is named Isospora manorinae n. sp. after its host, the yellow-throated miner (Manorina flavigula wayensis). PMID- 26821298 TI - Avian haemosporidian parasites (Haemosporida): A comparative analysis of different polymerase chain reaction assays in detection of mixed infections. AB - Mixed infections of different species and genetic lineages of haemosporidian parasites (Haemosporida) predominate in wildlife, and such infections are particularly virulent. However, currently used polymerase chain reaction (PCR) based detection methods often do not read mixed infections. Sensitivity of different PCR assays in detection of mixed infections has been insufficiently tested, but this knowledge is essential in studies addressing parasite diversity in wildlife. Here, we applied five different PCR assays, which are broadly used in wildlife avian haemosporidian research, and compared their sensitivity in detection of experimentally designed mixed infections of Haemoproteus and Plasmodium parasites. Three of these PCR assays use primer sets that amplify fragments of cytochrome b gene (cyt b), one of cytochrome oxidase subunit I (COI) gene, and one target apicoplast genome. We collected blood from wild-caught birds and, using microscopic and PCR-based methods applied in parallel, identified single infections of ten haemosporidian species with similar parasitemia. Then, we prepared 15 experimental mixes of different haemosporidian parasites, which often are present simultaneously in wild birds. Similar concentration of total DNA was used in each parasite lineage during preparation of mixes. Positive amplifications were sequenced, and the presence of mixed infections was reported by visualising double-base calling in sequence electropherograms. This study shows that the use of each single PCR assay markedly underestimates biodiversity of haemosporidian parasites. The application of at least 3 PCR assays in parallel detected the majority, but still not all lineages present in mixed infections. We determined preferences of different primers in detection of parasites belonging to different genera of haemosporidians during mixed infections. PMID- 26821300 TI - Erratum to: Possible Role of Trichophytin Antigen in Inducing Impaired Immunological Clearance of Fungus in Onychomycosis. PMID- 26821299 TI - Genetic loci on chromosome 5 are associated with circulating levels of interleukin-5 and eosinophil count in a European population with high risk for cardiovascular disease. AB - IL-5 is a Th2 cytokine which activates eosinophils and is suggested to have an atheroprotective role. Genetic variants in the IL5 locus have been associated with increased risk of CAD and ischemic stroke. In this study we aimed to identify genetic variants associated with IL-5 concentrations and apply a Mendelian randomisation approach to assess IL-5 levels for causal effect on intima-media thickness in a European population at high risk of coronary artery disease. We analysed SNPs within robustly associated candidate loci for immune, inflammatory, metabolic and cardiovascular traits. We identified 2 genetic loci for IL-5 levels (chromosome 5, rs56183820, BETA=0.11, P=6.73E(-5) and chromosome 14, rs4902762, BETA=0.12, P=5.76E(-6)) and one for eosinophil count (rs72797327, BETA=-0.10, P=1.41E(-6)). Both chromosome 5 loci were in the vicinity of the IL5 gene, however the association with IL-5 levels failed to replicate in a meta analysis of 2 independent cohorts (rs56183820, BETA=0.04, P=0.2763, I(2)=24, I(2) P=0.2516). No significant associations were observed between SNPs associated with IL-5 levels or eosinophil count and IMT measures. Expression quantitative trait analyses indicate effects of the IL-5 and eosinophil-associated SNPs on RAD50 mRNA expression levels (rs12652920 (r2=0.93 with rs56183820) BETA=-0.10, P=8.64E( 6) and rs11739623 (r2=0.96 with rs72797327) BETA=-0.23, P=1.74E(-29), respectively). Our data do not support a role for IL-5 levels and eosinophil count in intima-media thickness, however SNPs associated with IL-5 and eosinophils might influence stability of the atherosclerotic plaque via modulation of RAD50 levels. PMID- 26821301 TI - Correction: Multivariate analysis of electrophysiological diversity of Xenopus visual neurons during development and plasticity. PMID- 26821302 TI - DNA methylation perspectives in the pathogenesis of autoimmune diseases. AB - DNA methylation is now widely recognized as being critical to maintain the function of immune cells. Recent studies suggest that aberrant DNA methylation levels not only can result in immune cells autoreactivity in vitro, but also are related to autoimmunity in vivo. Environmental factors and genetic polymorphisms cause abnormal methylation, which affects the expression of certain immune related genes, being becoming hot spot of explaining the mechanism of autoimmune diseases. This paper reviews the importance of abnormal methylation during the development of common autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and type 1 diabetes, aiming at a better understanding of the pathogenesis of autoimmune diseases and providing new ideas for the treatment of these diseases. PMID- 26821303 TI - Oral insulin (human, murine, or porcine) does not prevent diabetes in the non obese diabetic mouse. AB - Studies have shown oral insulin prevents type 1 diabetes (T1D) in mouse models, however human trials were inconclusive. We tested the ability of different insulins to prevent T1D in non-obese diabetic mice. Mice received oral insulin or PBS twice weekly and disease was monitored. Contrary to previous studies, no insulin tested showed significant ability to prevent T1D, nor did testing of linked suppression in a delayed type hypersensitivity model have reproducible effect. To investigate delivery of antigen within the GI tract, blue dye was fed to mice. Dye traveled 5-8 cm from stomach to small intestine within 10s, suggesting orally administered antigen may not get digested in the stomach in mice. Insulin incubated with jejunum extracts was instantly digested. Thus, in humans large doses of insulin may be required to achieve tolerance as antigen may be more vulnerable to digestion in the stomach even before reaching the small intestine. PMID- 26821304 TI - Btk inhibition treats TLR7/IFN driven murine lupus. AB - Bruton's tyrosine kinase (Btk) is expressed in a variety of immune cells and previous work has demonstrated that blocking Btk is a promising strategy for treating autoimmune diseases. Herein, we utilized a tool Btk inhibitor, M7583, to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon. In BXSB-Yaa lupus mice, Btk inhibition reduced autoantibodies, nephritis, and mortality. In the pristane induced DBA/1 lupus model, Btk inhibition suppressed arthritis, but autoantibodies and the IFN gene signature were not significantly affected; suggesting efficacy was mediated through inhibition of Fc receptors. In vitro studies using primary human macrophages revealed that Btk inhibition can block activation by immune complexes and TLR7 which contributes to tissue damage in SLE. Overall, our results provide translational insight into how Btk inhibition may provide benefit to a variety of SLE patients by affecting both BCR and FcR signaling. PMID- 26821305 TI - Hepatitis C virus regulates the production of monocytic myeloid-derived suppressor cells from peripheral blood mononuclear cells through PI3K pathway and autocrine signaling. AB - Hepatitis C virus (HCV) infection is a major liver disease that ultimately develops into chronic hepatitis. Consequently, such patients are predisposed to serious complications, such as hepatocellular carcinoma. In HCV-infected patients, impaired T-cell responses are associated with persistent infection. Myeloid-derived suppressor cells (MDSCs) play a pivotal role in suppressing T cell responses. In this study, we investigated the capacity and mechanism through which HCV transforms CD14+ monocytes into monocytic (Mo)-MDSCs. We showed that HCV core protein promotes CD14+ monocytes to develop a CD14+HLA-DR/low phenotype with upregulated indoleamine 2,3-dioxygenase (IDO) expression and suppressed T cell proliferation. Importantly, HCV-induced Mo-MDSC production was attributed to the PI3K pathway via induction of IL-10 and TNF-alpha secretion. This process could be reversed by polyinosinic:polycytidylic acid (polyI:C) treatment. In conclusion, our results suggest that HCV regulates Mo-MDSC production from monocytes through the PI3K pathway and autocrine cytokines. The latter can serve as effective targets for novel HCV therapies. PMID- 26821306 TI - Obstetrical and Neonatal Perspectives on Prematurity. PMID- 26821307 TI - One-Dimensional RuO2/Mn2O3 Hollow Architectures as Efficient Bifunctional Catalysts for Lithium-Oxygen Batteries. AB - Rational design and massive production of bifunctional catalysts with fast oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) kinetics are critical to the realization of highly efficient lithium-oxygen (Li-O2) batteries. Here, we first exploit two types of double-walled RuO2 and Mn2O3 composite fibers, i.e., (i) phase separated RuO2/Mn2O3 fiber-in-tube (RM-FIT) and (ii) multicomposite RuO2/Mn2O3 tube-in-tube (RM-TIT), by controlling ramping rate during electrospinning process. Both RM-FIT and RM-TIT exhibited excellent bifunctional electrocatalytic activities in alkaline media. The air electrodes using RM-FIT and RM-TIT showed enhanced overpotential characteristics and stable cyclability over 100 cycles in the Li-O2 cells, demonstrating high potential as efficient OER and ORR catalysts. PMID- 26821308 TI - Poverty, disability and self-reported health amongst residents and migrants in Gauteng, South Africa. AB - BACKGROUND AND AIM: The aim of the present study was to assess the relative importance of individual- and household-level indicators of poverty to the self reported health of residents and recent migrants in South Africa's most urbanised province (Gauteng). SUBJECTS AND METHODS: Univariate and multivariable statistical analyses were undertaken on data from the 2014 Quality of Life household survey undertaken by the Gauteng City Regional Observatory. The survey generated data on a representative sample of n = 27 490 respondents. RESULTS: At the individual-level the odds for disability or health-limiting work/social activities was significantly lower amongst younger, better educated and employed respondents, and amongst both transnational and internal migrants. At the household-level, the absence of some basic services and household assets (particularly mains electricity, telecommunications and a television) were significantly associated with a lower odds of health-limiting work/social activities. CONCLUSIONS: Variation in sociodemographic and economic predictors of self-reported health at the individual- and household-level partly explain the lower odds of disability and health-limiting work/social activities of migrants, since migrants were less likely to be disabled and tended to be younger, with higher educational attainment and better employment status than residents, yet were also more likely to be living in households with fewer services and assets. PMID- 26821309 TI - Research and realization of ultrasonic gas flow rate measurement based on ultrasonic exponential model. AB - For ultrasonic gas flow rate measurement based on ultrasonic exponential model, when the noise frequency is close to that of the desired signals (called similar frequency noise) or the received signal amplitude is small and unstable at big flow rate, local convergence of the algorithm genetic-ant colony optimization 3cycles may appear, and measurement accuracy may be affected. Therefore, an improved method energy genetic-ant colony optimization-3cycles (EGACO-3cycles) is proposed to solve this problem. By judging the maximum energy position of signal, the initial parameter range of exponential model can be narrowed and then the local convergence can be avoided. Moreover, a DN100 flow rate measurement system with EGACO-3cycles method is established based on NI PCI-6110 and personal computer. A series of experiments are carried out for testing the new method and the measurement system. It is shown that local convergence doesn't appear with EGACO-3cycles method when similar-frequency noises exist and flow rate is big. Then correct time of flight can be obtained. Furthermore, through flow calibration on this system, the measurement range ratio is achieved 500:1, and the measurement accuracy is 0.5% with a low transition velocity 0.3 m/s. PMID- 26821310 TI - Radiation therapy-induced neuro-Sweet disease in a patient with oral squamous cell carcinoma. AB - Neurological involvement is a rare extracutanenous manifestation of Sweet's syndrome. We present a novel case of radiation therapy-induced neuro-Sweet disease in a patient receiving treatment for an oral squamous cell carcinoma. PMID- 26821311 TI - Differential Toxicity of Antibodies to the Prion Protein. AB - Antibodies against the prion protein PrPC can antagonize prion replication and neuroinvasion, and therefore hold promise as possible therapeutics against prion diseases. However, the safety profile of such antibodies is controversial. It was originally reported that the monoclonal antibody D13 exhibits strong target related toxicity, yet a subsequent study contradicted these findings. We have reported that several antibodies against certain epitopes of PrPC, including antibody POM1, are profoundly neurotoxic, yet antibody ICSM18, with an epitope that overlaps with POM1, was reported to be innocuous when injected into mouse brains. In order to clarify this confusing situation, we assessed the neurotoxicity of antibodies D13 and ICSM18 with dose-escalation studies using diffusion-weighted magnetic resonance imaging and various histological techniques. We report that both D13 and ICSM18 induce rapid, dose-dependent, on target neurotoxicity. We conclude that antibodies directed to this region may not be suitable as therapeutics. No such toxicity was found when antibodies against the flexible tail of PrPC were administered. Any attempt at immunotherapy or immunoprophylaxis of prion diseases should account for these potential untoward effects. PMID- 26821312 TI - Interference between adaptation to double steps and adaptation to rotated feedback in spite of differences in directional selectivity. AB - Two key features of sensorimotor adaptation are the directional selectivity of adaptive changes and the interference of adaptations to opposite directions. The present study investigated whether directional selectivity and interference of adaptation are related to executive functions and whether these phenomena differ between two methods for visuomotor adaptation. Subjects adapted at three target directions to clockwise or counterclockwise rotated feedback or to clockwise or counterclockwise target displacements (double steps). Both adaptation methods induce rotations of movement trajectories into the same direction, but provide visual information differently. The results showed that adaptation progressed differently between three targets. When movements adapted clockwise, adaptation was best at the most clockwise located target, and when movements adapted counterclockwise, it was best at the most counterclockwise located target, suggesting that spatial generalization between target directions is related to the direction of motor adaptation. The two adaptation methods produced different adaptation patterns, which indicate a further impact of visual information. A second adaptation to the other and opposite-directed discordance was worse than naive adaptation and washed out the aftereffects from the first adaptation, confirming that both adaptation methods interfered. Executive functions were significant covariate for overall interference and interference of target specific adaptation. The results suggest that directional selectivity of adaptation is shaped by the direction of motor adaptation and the visual information provided. The interference of both adaptation methods indicates that they share adaptive mechanisms for recalibration. The interference is the lower the better subjects are able to cognitively switch between tasks and to inhibit prepotent responses. Therefore, cognitive functions seem to be involved in the inhibition of non-adequate sensorimotor responses. PMID- 26821313 TI - Stimulation of the ventral tegmental area increased nociceptive thresholds and decreased spinal dorsal horn neuronal activity in rat. AB - Deep brain stimulation has been found to be effective in relieving intractable pain. The ventral tegmental area (VTA) plays a role not only in the reward process, but also in the modulation of nociception. Lesions of VTA result in increased pain thresholds and exacerbate pain in several pain models. It is hypothesized that direct activation of VTA will reduce pain experience. In this study, we investigated the effect of direct electrical stimulation of the VTA on mechanical, thermal and carrageenan-induced chemical nociceptive thresholds in Sprague-Dawley rats using our custom-designed wireless stimulator. We found that: (1) VTA stimulation itself did not show any change in mechanical or thermal threshold; and (2) the decreased mechanical and thermal thresholds induced by carrageenan injection in the hind paw contralateral to the stimulation site were significantly reversed by VTA stimulation. To further explore the underlying mechanism of VTA stimulation-induced analgesia, spinal cord dorsal horn neuronal responses to graded mechanical stimuli were recorded. VTA stimulation significantly inhibited dorsal horn neuronal activity in response to pressure and pinch from the paw, but not brush. This indicated that VTA stimulation may have exerted its analgesic effect via descending modulatory pain pathways, possibly through its connections with brain stem structures and cerebral cortex areas. PMID- 26821314 TI - Motor imagery training promotes motor learning in adolescents with cerebral palsy: comparison between left and right hemiparesis. AB - This experiment was designed to evaluate the effects of pure motor imagery training (MIT) and its combination with physical practice on learning an aiming task with the more affected arm in adolescents suffering from cerebral palsy. Effect of MIT was evaluated as a function of side of hemiparesis. The experiment was accomplished by 11- to 16-year-old participants (M = 13.58 years), who suffered left (n = 16) or right (n = 15) mild hemiparesis. They were exposed to pure MIT (day 1) followed by physical practice (day 2) on an aiming task demanding movement accuracy and speed. Posttraining movement kinematics of the group receiving MIT were compared with movement kinematics of the control group after receiving recreational activities (day 1) and physical practice (day 2). Kinematic analysis showed that MIT led to decreased movement time and straighter hand displacements to the target. Performance achievements from MIT were increased with further physical practice, leading to enhanced effects on motor learning. Retention evaluation indicated that performance improvement from pure MIT and its combination with physical practice were stable over time. Performance achievements were equivalent between adolescents with either right or left hemiparesis, suggesting similar capacity between these groups to achieve performance improvement from pure imagery training and from its association with physical practice. Our results suggest that motor imagery training is a procedure potentially useful to increase motor learning achievements in individuals suffering from cerebral palsy. PMID- 26821315 TI - Event-related fields evoked by vocal response inhibition: a comparison of younger and older adults. AB - The current study examined event-related fields (ERFs) evoked by vocal response inhibition in a stimulus-selective stop-signal task. We compared inhibition related ERFs across a younger and an older group of adults. Behavioural results revealed that stop-signal reaction times (RTs), go-RTs, ignore-stop RTs and failed stop RTs were longer in the older, relative to the younger group by 38, 123, 149 and 116 ms, respectively. The amplitude of the ERF M2 peak (approximately 200 ms after the stop signal) evoked on successful stop trials was larger compared to that evoked on both failed stop and ignore-stop trials. The M4 peak (approximately 450 ms after stop signal) was of larger amplitude in both successful and failed stops compared to ignore-stop trials. In the older group, the M2, M3 and M4 peaks were smaller in amplitude and peaked later in time (by 24, 50 and 76 ms, respectively). We demonstrate that vocal response inhibition related ERFs exhibit a similar temporal evolution to those previously described for manual response inhibition: an early peak at 200 ms (i.e. M2) that differentiates successful from failed stopping, and a later peak (i.e. M4) that is consistent with a neural marker of response checking and error processing. Across groups, our data support a more general decline of stimulus processing speed with age. PMID- 26821316 TI - The effects of transcranial direct current stimulation over the dorsolateral prefrontal cortex on cognitive inhibition. AB - The present study examines the effects of bilateral transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) (anodal over left and cathodal over right DLPFC). This study describes the long-term effects of tDCS on cognitive inhibition, using the Hayling task. Twenty volunteers participated in the study and were assigned to either an active or a sham group. Participants heard sentences with the final word missing. They were asked then to complete the sentence with a word that either is appropriate in the context of the sentence (initiation condition) or is completely unrelated in this specific context (suppression condition). All participants performed a baseline Hayling task followed by six stimulation sessions. Subsequent to completion of these stimulations, we assessed immediately Hayling performance and re-assessed this performance 1 month. The results indicate a significant decrease in the number of errors in the active group, but only in the suppression condition that continued for 1 month after the sixth stimulation. The current findings suggest that tDCS can improve cognitive inhibition for the long-term in healthy adults and that the DLPFC has a special role in selecting the correct response and suppressing irrelevant semantic information. PMID- 26821317 TI - Asymmetric interference in left-handers during bimanual movements reflects switch in lateralized control characteristics. AB - Interactions between the hands are a collateral of simultaneous bimanual movements and can inform us about the functional asymmetries of the dominant and nondominant hemisphere-effector systems. Few studies on bimanual coordination have focused on discrete movement control, and even fewer have looked at this in the context of handedness. Using a novel bimanual paradigm in which both hands perform simultaneous target-directed movements, this study addressed interference between the hands in two groups of left-handed individuals. In one group, the dominant hand was perturbed, and in the other, the nondominant hand; the respective contralateral hand moved without visual feedback. Results show that the kinematic perturbation of the dominant left hand resulted in directional interference in the nonvisible right hand. Similarly to previous studies using this bimanual paradigm, interference became manifest through isodirectional deviations in the nonvisible hand in the majority of participants. The findings mirror the results of a previous study in right-handers. At the same time, interference was overall weaker in the left-handers, and not as exclusively dominant to nondominant as in the previous right-handed sample. The results not only confirm that hand control characteristics switch with handedness, but also shape interactions between the hands accordingly in left-handers. PMID- 26821318 TI - Familiar environments enhance object and spatial memory in both younger and older adults. AB - Recent evidence suggests that familiarity with an environment may protect against spatial memory decline for familiar objects in older adults. We investigated whether a familiar context also reduces age-related decline in spatial memory for novel objects. Twenty-four younger and 23 older participants viewed a virtual rendering of a local environment along two different routes, each through a well known (West) or lesser-known (East) area within the environment. Older and younger participants reported being more familiar with one (i.e. West) area than the other. In each trial, participants were presented with one route and were instructed to learn ten novel objects and their locations along the route. Following learning, participants immediately completed five test blocks: an object recognition task, an egocentric spatial processing (direction judgement) task, an allocentric spatial processing (proximity judgement) task and two pen and-paper tests to measure cognitive mapping abilities. First we found an age effect with worse performance by older than younger adults in all spatial tasks, particularly in allocentric spatial processing. However, our results suggested better memory for objects and directions, but not proximity judgements, when the task was associated with more familiar than unfamiliar contexts, in both age groups. There was no benefit of context when a separate young adult group (N = 24) was tested, who reported being equally familiar with both areas. These results suggest an important facilitatory role of context familiarity on object recognition, and in particular egocentric spatial memory, and have implications for enhancing spatial memory in older adults. PMID- 26821319 TI - Different damping responses explain vertical endpoint error differences between visual conditions. AB - Upright people making goal-directed movements in dark environments often vertically undershoot remembered target locations when compared to performances in illuminated environments. In this study, we wanted to determine whether influences of the gravitational pull and/or type of muscle activation could explain differences in vertical endpoint precision between movements to visually remembered target locations with and without allocentric cues available. We also used a simple damping model for movement trajectories to describe potential differences in behavior between visual conditions. Subjects performed straight arm pointing movements to REAL target locations or remembered target locations in darkness (DARK) or normal room lighting (LIGHT). Performances were made from UPRIGHT and INVERTED (upside down) body orientations. Starting arm position (UP by the ear; DOWN on the thigh) also varied so that eccentric or concentric muscle contractions for arm flexion or extension movements occurred primarily along the earth-fixed vertical either with or against the gravitational pull. Effects of visual condition (LIGHT, DARK), body orientation (UPRIGHT, INVERTED), starting arm position (UP, DOWN), and target level (Near, Middle, Far) on elevation endpoint errors revealed that subject's errors in the DARK were more negative than those in the LIGHT. Errors correlated well with movement displacement to reveal the common vertical undershooting bias in darkness exacerbated by inverting the body or requiring greater movement excursions. Although influences of gravitational pull and muscle activation type could not explain differences between visual conditions, modeling revealed critically damped behavior in the DARK and under-damped behavior in the LIGHT to indicate muscle energy dissipation without vision. PMID- 26821320 TI - Decision theory, motor planning, and visual memory: deciding where to reach when memory errors are costly. AB - Limitations in visual working memory (VWM) have been extensively studied in psychophysical tasks, but not well understood in terms of how these memory limits translate to performance in more natural domains. For example, in reaching to grasp an object based on a spatial memory representation, overshooting the intended target may be more costly than undershooting, such as when reaching for a cup of hot coffee. The current body of literature lacks a detailed account of how the costs or consequences of memory error influence what we encode in visual memory and how we act on the basis of remembered information. Here, we study how externally imposed monetary costs influence behavior in a motor decision task that involves reach planning based on recalled information from VWM. We approach this from a decision theoretic perspective, viewing decisions of where to aim in relation to the utility of their outcomes given the uncertainty of memory representations. Our results indicate that subjects accounted for the uncertainty in their visual memory, showing a significant difference in their reach planning when monetary costs were imposed for memory errors. However, our findings indicate that subjects memory representations per se were not biased by the imposed costs, but rather subjects adopted a near-optimal post-mnemonic decision strategy in their motor planning. PMID- 26821321 TI - Interleukin-6 promoter polymorphism interacts with pain and life stress influencing depression phenotypes. AB - Interleukin-6 (IL-6) has emerged as a potent biomarker for depression as its elevated plasma levels in patients with clinical depression have been confirmed by meta-analyses. Increased plasma IL-6 concentration was associated with various psychological stress factors and physical disorders accompanied by pain. Another modulator of the IL-6 level is rs1800795, a promoter polymorphism in the IL-6 gene which is able to influence its expression rate. Therefore, we examined in a Hungarian population sample of 1053 volunteers with European origins if rs1800795 polymorphism can affect depression symptoms measured by Zung Self-rating Depression Scale (ZSDS), and Brief Symptom Inventory (BSI). We also investigated the interactions of the polymorphism with reported painful physical conditions and Recent Negative Life Events (RLE) measured by the List of Life Threatening Experiences. Rs1800795 significantly interacted with both RLE and painful condition on depressive symptoms measured by ZSDS and BSI using different heritability models, while no main effects of the polymorphism were identified. After correction for multiple testing only the rs1800795 * RLE interaction effect (recessive model) remained significant on the BSI score, while both RLE and painful conditions significantly interacted on the ZSDS. In conclusion, the functional IL-6 rs1800795 polymorphism in interaction with various stress factors increases the risk of depression and has a greater impact on symptoms measured by the ZSDS. Thus, IL-6 and other cytokines may be more relevant in the development of somatic symptoms compared to affective signs of depression, delineating a specific genotype-phenotype relationship in this heterogeneous disorder. PMID- 26821322 TI - Synergistic Effects of ACE Insertion/Deletion and GNB3 C825T Polymorphisms on the Efficacy of PDE-5 Inhibitor in Patients with Pulmonary Hypertension. AB - BACKGROUND: The insertion/deletion (I/D) polymorphism in the angiotensin converting enzyme gene (ACE) and the C825T polymorphism in the G-protein beta3 subunit gene (GNB3) are associated with the efficacy of phosphodiesterase-5 inhibitor (PDE-5I) in erectile dysfunction. In addition, GNB3 genotypes could be associated with clinical worsening in pulmonary hypertension (PH) treated with PDE-5I. However, no studies have described the synergistic effects of gene polymorphisms on drug efficacy in patients with PH. OBJECTIVES: We aimed to examine the effects of combined ACE/GNB3 polymorphisms on the efficacy of PDE-5I in patients with PH. METHODS: This was a retrospective uncontrolled study. Ninety patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic PH (CTEPH) were treated with PDE-5I. Freedom from clinical worsening and pre- and post-treatment parameters, including the 6-min walk distance (6MWD) and serum brain natriuretic peptide (BNP) levels, were compared between patients with ACE/GNB3 II/TT and non-II/TT genotypes. RESULTS: Time to clinical worsening was significantly longer in patients with the II/TT genotype than in those with the non-II/TT genotype (5-year freedom from clinical worsening: 100 vs. 48.8%, respectively; p = 0.018), even in patients with CTEPH alone. Post-treatment 6MWD and BNP levels in patients with the II/TT genotype tended to be better than those in patients with the non-II/TT genotype. The ACE/GNB3 genotype was a significant predictor of clinical worsening, even after adjusting for pulmonary vascular resistance and 6MWD. CONCLUSIONS: ACE and GNB3 polymorphisms may synergistically influence the efficacy of PDE-5I in patients with PH. PMID- 26821324 TI - Studying Coxiella burnetii Type IV Substrates in the Yeast Saccharomyces cerevisiae: Focus on Subcellular Localization and Protein Aggregation. AB - Coxiella burnetii is a Gram-negative obligate parasitic bacterium that causes the disease Q-fever in humans. To establish its intracellular niche, it utilizes the Icm/Dot type IVB secretion system (T4BSS) to inject protein effectors into the host cell cytoplasm. The host targets of most cognate and candidate T4BSS translocated effectors remain obscure. We used the yeast Saccharomyces cerevisiae as a model to express and study six C. burnetii effectors, namely AnkA, AnkB, AnkF, CBU0077, CaeA and CaeB, in search for clues about their role in C. burnetii virulence. When ectopically expressed in HeLa cells, these effectors displayed distinct subcellular localizations. Accordingly, GFP fusions of these proteins produced in yeast also decorated distinct compartments, and most of them altered cell growth. CaeA was ubiquitinated both in yeast and mammalian cells and, in S. cerevisiae, accumulated at juxtanuclear quality-control compartments (JUNQs) and insoluble protein deposits (IPODs), characteristic of aggregative or misfolded proteins. AnkA, which was not ubiquitinated, accumulated exclusively at the IPOD. CaeA, but not AnkA or the other effectors, caused oxidative damage in yeast. We discuss that CaeA and AnkA behavior in yeast may rather reflect misfolding than recognition of conserved targets in the heterologous system. In contrast, CBU0077 accumulated at vacuolar membranes and abnormal ER extensions, suggesting that it interferes with vesicular traffic, whereas AnkB associated with the yeast nucleolus. Both effectors shared common localization features in HeLa and yeast cells. Our results support the idea that C. burnetii T4BSS effectors manipulate multiple host cell targets, which can be conserved in higher and lower eukaryotic cells. However, the behavior of CaeA and AnkA prompt us to conclude that heterologous protein aggregation and proteostatic stress can be a limitation to be considered when using the yeast model to assess the function of bacterial effectors. PMID- 26821323 TI - Analysis of Host Gene Expression Profile in HIV-1 and HIV-2 Infected T-Cells. AB - HIV replication is closely regulated by a complex pathway of host factors, many of them being determinants of cell tropism and host susceptibility to HIV infection. These host factors are known to exert a positive or negative influence on the replication of the two major types of HIV, HIV-1 and HIV-2, thereby modulating virus infectivity, host response to infection and ultimately disease progression profiles characteristic of these two types. Understanding the differential regulation of host cellular factors in response to HIV-1 and HIV-2 infections will help us to understand the apparent differences in rates of disease progression and pathogenesis. This knowledge would aid in the discovery of new biomarkers that may serve as novel targets for therapy and diagnosis. The objective of this study was to determine the differential expression of host genes in response to HIV-1/HIV-2 infection. To achieve this, we analyzed the effects of HIV-1 (MN) and HIV-2 (ROD) infection on the expression of host factors in PBMC at the RNA level using the Agilent Whole Human Genome Oligo Microarray. Differentially expressed genes were identified and their biological functions determined. Host gene expression profiles were significantly changed. Gene expression profiling analysis identified a subset of differentially expressed genes in HIV-1 and HIV-2 infected cells. Genes involved in cellular metabolism, apoptosis, immune cell proliferation and activation, cytokines, chemokines, and transcription factors were differentially expressed in HIV-1 infected cells. Relatively few genes were differentially expressed in cells infected with HIV-2. PMID- 26821325 TI - Assessment of polycyclic aromatic hydrocarbons in indoor dust from varying categories of rooms in Changchun city, northeast China. AB - Sixteen polycyclic aromatic hydrocarbons (PAHs) were isolated from indoor dust from various categories of rooms in Changchun city, northeast China, including dormitory, office, kitchen, and living rooms. PAH concentrations ranged from 33.9 to 196.4 MUg g-1 and 21.8 to 329.6 MUg g-1 during summer and winter, respectively, indicating that total PAH concentrations in indoor dust are much higher than those in other media from the urban environment, including soils and sediments. The percentage of five- to six-ring PAHs was high, indicating that PAHs found in indoor dust mainly originate from pyrolysis rather than a petrogenic source. Rooms were divided into three groups using cluster analysis on the basis of 16 PAH compositions, namely smoke-free homes, homes exposed to smoke and offices. Results showed that the source of PAHs in smoke-free residential homes is primarily the burning of fossil fuels. In addition to the burning of fossil fuels, biomass combustion and cooking contributed to PAHs in houses exposed to smoke (including kitchens). Motor vehicles are an additional source of PAHs in offices because of greater interactions with the outdoor environment. The results of health risk assessment showed that the cancer risk levels by dermal contact and ingestion are 104- to 105-fold higher than that by inhalation, suggesting that ingestion and dermal contact of carcinogenic PAHs in dust are more important exposure routes than inhalation of PAHs from air. Although the results showed high potential of PAH concentrations in indoor dust in Changchun for human health risk, caution should be taken to evaluate the risk of PAHs calculated by USEPA standard models with default parameters because habitation styles are different in various categories of rooms. PMID- 26821326 TI - [Thymus cancers: A clinical observation]. AB - INTRODUCTION: Thymic tumors including thymomas, thymic carcinomas, and thymic carcinoid tumors are rare tumors with an incidence of 0.13/100,000. MATERIALS AND METHODS: A literature search was performed to identify recent findings on epidemiology, classification, and various therapeutic approaches. RESULTS: These tumors with a wide spectrum of histologic and biologic features may be clinically unapparent for a long time or show a very aggressive behavior with local invasion and distant metastases. Surgical resection is the mainstay in stage I and II thymomas, whereas in stage III thymomas and in thymomas with pleural dissemination surgery in context of a multimodal treatment should be discussed. Thymic tumors are chemoreactive. Targeted therapies show poor results and should only be considered in the palliative situation after failure of chemotherapy. CONCLUSION: The new TNM (T: tumor, N: node, M: metastasis) classification of thymic tumors will help to identify the best treatment options. PMID- 26821327 TI - [Uropathology]. PMID- 26821328 TI - Antidepressant-like effect of Ikwitang involves modulation of monoaminergic systems. AB - Depression is a chronic mental disorder. Inflammatory reactions have an important function in the pathophysiology of depression. Ikwitang (IW) has been used to treat fever and inflammatory diseases, however, its effect on depression has not been previously investigated. Therefore, the present study evaluated the possible antidepressant-like effect of IW using a forced swimming test (FST) in mice. IW was orally administered for 14 days. On the 14 day, IW was administered 1 h prior to the FST. The immobility durations of the IW groups (0.01, 0.1 and 1 g/kg) were significantly decreased, compared with those of the distilled water (D.W.) groups. The reduction of immobility duration by IW was associated with significant increases in the levels of serotonin, noradrenaline and estrogen receptor-beta in the brain. IW significantly increased the levels of brain derived neurotrophic factor and phosphorylated extracellular signal-regulated kinases, compared with the D.W. groups. In addition, the levels of inflammatory cytokines were significantly reduced following IW administration in the hippocampus and serum. In conclusion, the results of the present study suggested that the antidepressant effect of IW may be associated with the modulation of monoaminergic systems and inflammatory reactions. PMID- 26821329 TI - (129)I record of nuclear activities in marine sediment core from Jiaozhou Bay in China. AB - Iodine-129 has been used as a powerful tool for environmental tracing of human nuclear activities. In this work, a sediment core collected from Jiaozhou Bay, the east coast of China, in 2002 was analyzed for (129)I to investigate the influence of human nuclear activities in this region. Significantly enhanced (129)I level was observed in upper 70 cm of the sediment core, with peak values in the layer corresponding to 1957, 1964, 1974, 1986, and after 1990. The sources of (129)I and corresponding transport processes in this region are discussed, including nuclear weapons testing at the Pacific Proving Grounds, global fallout from a large numbers of nuclear weapon tests in 1963, the climax of Chinese nuclear weapons testing in the early 1970s, the Chernobyl accident in 1986, and long-distance dispersion of European reprocessing derived (129)I. The very well (129)I records of different human nuclear activities in the sediment core illustrate the potential application of (129)I in constraining ages and sedimentation rates of the recent sediment. The releases of (129)I from the European nuclear fuel reprocessing plants at La Hague (France) and Sellafield (UK) were found to dominate the inventory of (129)I in the Chinese sediments after 1990, not only the directly atmospheric releases of these reprocessing plants, but also re-emission of marine discharged (129)I of these reprocessing plants in the highly contaminated European seas. PMID- 26821330 TI - Influence of oestrogen deficiency on the development of apical periodontitis. AB - AIM: To evaluate the effects of a long period of oestrogen deficiency on the development of apical periodontitis in rats. METHODOLOGY: Wistar rats (n = 24), 3 months old, evaluated by vaginal cytology, were included in the study. Twelve animals were ovariectomized (OVX group) and the other 12 were sham operated (control group). One hundred and twenty days after castration, the pulps of the left mandibular first molars were exposed to induce the development of apical periodontitis. Body mass was verified on a weekly basis. Following 21 and 40 days of lesion induction, the animals were sacrificed. Blood was collected for biochemical analysis, and mandibles were removed for radiographic analysis. Comparative analysis of the data was performed by the nonparametric Kruskal Wallis and Dunn's multiple-comparisons tests. The t-test was applied to compare the oestrogen levels between control and OVX groups. RESULTS: Radiographs revealed that apical periodontitis lesions were significantly larger in the 40 day OVX group when compared with both 40-day (P < 0.05) and 21-day (P < 0.001) control groups. Serum oestrogen levels were significantly lower in the OVX group (P < 0.01), confirming the efficacy of castration. Oestrogen deficiency resulted in significantly greater body mass gain (P < 0.01) in 40-day OVX group when compared with 40-day control group. Serum concentrations of calcium were similar between groups (P > 0.05). Alkaline phosphatase levels, although higher in the OVX groups (21 and 40 days), were not significantly different. CONCLUSIONS: Ovariectomized rats had significantly larger apical periodontitis lesions after 40 days of pulp exposure when compared with controls. These findings suggest that bone alterations as a result of long periods of oestrogen deficiency can influence the progression of apical periodontitis. PMID- 26821331 TI - Exposures to environmental phenols in Southern California firefighters and findings of elevated urinary benzophenone-3 levels. AB - Firefighters are at increased risk for exposure to toxic chemicals compared to the general population, but few studies of this occupational group have included biomonitoring. We measured selected phenolic chemicals in urine collected from 101 Southern California firefighters. The analytes included bisphenol A (BPA), triclosan, benzophenone-3 (BP-3), and parabens, which are common ingredients in a range of consumer products. BP-3, BPA, triclosan, and methyl paraben were detected in almost all study subjects (94-100%). The BP-3 geometric mean for firefighters was approximately five times higher than for a comparable National Health and Nutrition Examination Survey (NHANES) subgroup. Demographic and exposure data were collected from medical records and via a questionnaire, and covariates were examined to assess associations with BP-3 levels. BP-3 levels were elevated across all firefighter age groups, with the highest levels observed in the 35 to 39year old group. Body fat percentage had a significant inverse association with BP-3 concentrations. Our results indicate pervasive exposure to BP-3, BPA, triclosan, and methyl paraben in this population of firefighters, consistent with studies of other populations. Further research is needed to investigate possible explanations for the higher observed BP-3 levels, such as occupational or California-specific exposures. PMID- 26821332 TI - Genetic Burden Analyses of Phenotypes Relevant to Aging in the Berlin Aging Study II (BASE-II). AB - BACKGROUND: Body mass index (BMI), bone mineral density (BMD), and telomere length are phenotypes that modulate the course of aging. Over 40% of their phenotypic variance is determined by genetics. Genome-wide association studies (GWAS) have recently uncovered >100 independent single-nucleotide polymorphisms (SNPs) showing genome-wide significant (p < 5 * 10-8) association with these traits. OBJECTIVE: To test the individual and combined impact of previously reported GWAS SNPs on BMI, BMD, and relative leukocyte telomere length (rLTL) in ~1,750 participants of the Berlin Aging Study II (BASE-II), a cohort consisting predominantly of individuals >60 years of age. METHODS: Linear regression analyses were performed on a total of 101 SNPs and BMI, BMD measurements of the femoral neck (FN) and lumbar spine (LS), and rLTL. The combined effect of all trait-specific SNPs was evaluated by generating a weighted genomic profile score (wGPS) used in the association analyses. The predictive capability of the wGPS was estimated by determining the area under the receiver operating curve (AUC) for osteoporosis status (determined by BMD) with and without the wGPS. RESULTS: Five loci showed experiment-wide significant association with BMI (FTO rs1558902, p = 1.80 * 10-5) or BMD (MEPE rs6532023, pFN = 5.40 * 10-4, pLS = 1.09 * 10-4; TNFRSF11B rs2062377, pLS = 8.70 * 10-4; AKAP11 rs9533090, pLS = 1.05 * 10-3; SMG6 rs4790881, pFN = 3.41 * 10-4) after correction for multiple testing. Several additional loci showed nominally significant (p < 0.05) association with BMI and BMD. The trait-specific wGPS was highly significantly associated with BMD (p < 2 * 10-16) and BMI (p = 1.10 * 10-6). No significant association was detected for rLTL in either single-SNP or wGPS-based analyses. The AUC for osteoporosis improved modestly from 0.762 (95% CI 0.733-0.800) to 0.786 (95% CI 0.756-0.823) and 0.785 (95% CI 0.757-0.824) upon inclusion of the FN- and LS-BMD wGPS, respectively. CONCLUSION: Our study provides an independent validation of previously reported genetic association signals for BMI and BMD in the BASE-II cohort. Additional studies are needed to pinpoint the factors underlying the proportion of phenotypic variance that remains unexplained by the current models. PMID- 26821333 TI - Elucidation of structural and functional properties of albumin bound to gold nanoparticles. AB - Nanoparticle-albumin complexes are being designed for targeted drug delivery and imaging. However, the changes in the functional properties of albumin due to adsorption on nanoparticles remain elusive. Thus, the objective of this work was to elucidate the structural and functional properties of human and bovine serum albumin bound to negatively charged gold nanoparticles (GNPs). Fluorescence data demonstrated static quenching of albumin by GNP with the quenching of buried as well as surface tryptophan in BSA. The binding process was enthalpy and entropy driven in HSA and BSA, respectively. At lower concentrations of GNP there was a higher affinity for tryptophan, whereas at higher concentrations both tryptophan and tyrosine participated in the interaction. Synchronous fluorescence spectra revealed that the microenvironment of tryptophan in HSA turned more hydrophilic upon exposure to GNP. The alpha-helical content of albumin was unaltered by GNP. Approximately 37 and 23% reduction in specific activity of HSA and BSA was observed due to GNP binding. In presence of warfarin and ibuprofen the binding constants of albumin-GNP complexes were altered. A very interesting observation not reported so far is the retained antioxidant activity of albumin in presence of GNP i.e. we believe that GNPs did not bind to the free sulfhydryl groups of albumin. However enhanced levels of copper binding were observed. We have also highlighted the differential response in albumin due to gold and silver nanoparticles which could be attributed to differences in the charge of the nanoparticle. PMID- 26821334 TI - Safflower yellow B suppresses HepG2 cell injury induced by oxidative stress through the AKT/Nrf2 pathway. AB - Oxidative stress plays an important role in the pathogenesis of various liver diseases. Safflower yellow B (SYB) has been reported to protect the brain against damage induced by oxidative stress; however, whether SYB can also protect hepatocytes from oxidative stress remains unknown. In the present study, to determine whether pre-treatment with SYB reduces hydrogen peroxide (H2O2)-induced oxidative stress in HepG2 cells, we investigated H2O2-induced oxidative damage to HepG2 cells treated with or without SYB. Cell viability was measured by MTT assay and cytotoxicity was evaluated by lactate dehydrogenase (LDH) assay. The activities of the antioxidant enzymes, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were determined using respective kits. Intracellular reactive oxygen species (ROS) accumulation in the HepG2 cells was monitored using the fluorescent marker, 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA). Cell apoptosis was evaluated by determining the activity of caspase-3 and by Annexin V/propidium iodide (PI) double staining. Protein expression levels were measured by western blot analysis, and the levels of related cellular kinases were also determined. H2O2 induced pronounced injury to the HepG2 cells, as evidenced by increased levels of malondialdehyde (MDA) and ROS, the decreased activity of SOD and GSH-Px, the increased activitation of caspase-3 and cell apoptosis, and the loss of mitochondrial membrane potential. SYB significantly inhibited the damaging effects of H2O2, indicating that it protected the cells against H2O2-induced oxidative damage. Moreover, pre-treatment with SYB increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and NAD(P)H dehydrogenase, quinone 1 (NQO1) which are peroxiredoxins. SYB also significantly increased the phosphorylation of AKT. However, this inductive effect was blunted in the presence of the AKT inhibitor, LY294002. The findings of our study suggest that the activation of the AKT/Nrf2 pathway is involved in the cytoprotective effects of SYB against oxidative stress. Our findings provide new insight into the cytoprotective effects of SYB and the possible mechanisms underlying these effects. Thus, SYB may prove to be of therapeutic value for the treatment of various liver diseases. PMID- 26821336 TI - Revisiting the cost-effectiveness of universal cervical length screening: importance of progesterone efficacy. AB - BACKGROUND: Preterm birth (PTB) is a significant cause of neonatal morbidity and mortality. Studies have shown that vaginal progesterone therapy for women diagnosed with shortened cervical length can reduce the risk of PTB. However, published cost-effectiveness analyses of vaginal progesterone for short cervix have not considered an appropriate range of clinically important parameters. OBJECTIVE: To evaluate the cost-effectiveness of universal cervical length screening in women without a history of spontaneous PTB, assuming that all women with shortened cervical length receive progesterone to reduce the likelihood of PTB. STUDY DESIGN: A decision analysis model was developed to compare universal screening and no-screening strategies. The primary outcome was the cost effectiveness ratio of both the strategies, defined as the estimated patient cost per quality-adjusted life-year (QALY) realized by the children. One-way sensitivity analyses were performed by varying progesterone efficacy to prevent PTB. A probabilistic sensitivity analysis was performed to address uncertainties in model parameter estimates. RESULTS: In our base-case analysis, assuming that progesterone reduces the likelihood of PTB by 11%, the incremental cost effectiveness ratio for screening was $158,000/QALY. Sensitivity analyses show that these results are highly sensitive to the presumed efficacy of progesterone to prevent PTB. In a 1-way sensitivity analysis, screening results in cost-saving if progesterone can reduce PTB by 36%. Additionally, for screening to be cost effective at WTP=$60,000 in three clinical scenarios, progesterone therapy has to reduce PTB by 60%, 34% and 93%. Screening is never cost-saving in the worst-case scenario or when serial ultrasounds are employed, but could be cost-saving with a two-day hospitalization only if progesterone were 64% effective. CONCLUSION: Cervical length screening and treatment with progesterone is a not a dominant, cost-effective strategy unless progesterone is more effective than has been suggested by available data for US women. Until future trials demonstrate greater progesterone efficacy, and effectiveness studies confirm a benefit from screening and treatment, the cost-effectiveness of universal cervical length screening in the United States remains questionable. PMID- 26821337 TI - Ultrasonographic approach to diagnosis of fetal inflammatory response syndrome: a tool for at-risk fetuses? AB - Preterm parturition is a syndrome that may result from many underlying mechanisms. Infection and inflammation are the prominent ones. Intrauterine infection and inflammation have an effect akin to sepsis, and that is similar to systemic inflammatory response in adults. Indeed, there is evidence to support the association of a fetal inflammatory response syndrome (FIRS) to systemic infection and inflammation. The utilization of invasive procedures for the prenatal diagnosis of FIRS is associated with a risk for complications resulting from the invasive method. The progress in the imaging quality of obstetrical ultrasound and the development of novel methods for functional anatomical assessment of the fetal organs may help to identify, noninvasively, fetuses at risk for FIRS in patients presenting with preterm labor. We review the studies describing advanced sonographic modalities and the imaging findings in the heart, thymus, kidney, adrenal glands, and spleen of these fetuses. PMID- 26821335 TI - Vascular Reactivity Profile of Novel KCa 3.1-Selective Positive-Gating Modulators in the Coronary Vascular Bed. AB - Opening of intermediate-conductance calcium-activated potassium channels (KC a 3.1) produces membrane hyperpolarization in the vascular endothelium. Here, we studied the ability of two new KC a 3.1-selective positive-gating modulators, SKA 111 and SKA-121, to (1) evoke porcine endothelial cell KC a 3.1 membrane hyperpolarization, (2) induce endothelium-dependent and, particularly, endothelium-derived hyperpolarization (EDH)-type relaxation in porcine coronary arteries (PCA) and (3) influence coronary artery tone in isolated rat hearts. In whole-cell patch-clamp experiments on endothelial cells of PCA (PCAEC), KC a currents evoked by bradykinin (BK) were potentiated ~7-fold by either SKA-111 or SKA-121 (both at 1 MUM) and were blocked by a KC a 3.1 blocker, TRAM-34. In membrane potential measurements, SKA-111 and SKA-121 augmented bradykinin-induced hyperpolarization. Isometric tension measurements in large- and small-calibre PCA showed that SKA-111 and SKA-121 potentiated endothelium-dependent relaxation with intact NO synthesis and EDH-type relaxation to BK by ~2-fold. Potentiation of the BK response was prevented by KC a 3.1 inhibition. In Langendorff-perfused rat hearts, SKA-111 potentiated coronary vasodilation elicited by BK. In conclusion, our data show that positive-gating modulation of KC a 3.1 channels improves BK induced membrane hyperpolarization and endothelium-dependent relaxation in small and large PCA as well as in the coronary circulation of rats. Positive-gating modulators of KC a 3.1 could be therapeutically useful to improve coronary blood flow and counteract impaired coronary endothelial dysfunction in cardiovascular disease. PMID- 26821338 TI - Patterned, tubular scaffolds mimic longitudinal and radial mechanics of the neonatal trachea. AB - Tracheal damage, abnormality or absence can result from the growth of tumors or from Congenital High Airway Obstruction Syndrome. No optimal or routine treatment has been established for tracheal repair, despite numerous attempts with natural and artificial prostheses. The fetal trachea is comprised of cartilaginous rings connected by an elastomeric tissue. In an effort to design an engineered trachea replacement, we have synthesized 2-hydroxyethyl methacrylate hydrogels with moduli of 67 +/- 3.1 kPa (soft) and 13.0 +/- 1.8 MPa (hard). Given the criteria for longitudinal extensibility and lateral rigidity applied during respiration, we evaluated a series of patterned hydrogels with different sizes of hard and soft segments to mimic fetal tracheas. A 1:2 ratio of soft:hard segments resulted in a construct capable of 11.0 +/- 1% extension within the elastic range. Tubular constructs with this ratio required similar load/length for cyclic compression as ovine trachea samples. Achieving biomimetic mechanical properties in a trachea replacement may be essential for achieving normal respiration in recipient patients. STATEMENT OF SIGNIFICANCE: Fetal abnormalities or tumors can result in tracheal absence or damage. Despite numerous attempts with natural and artificial replacements, there is still no routine treatment for tracheal repair. The literature recognizes the importance of tracheal lateral rigidity and longitudinal extensibility for normal respiration. Achieving closely matched mechanical properties may provide proper function and help decrease implant fibrosis and subsequent occlusion. In this study, we evaluated the mechanics of a series of patterned, tubular hydrogels with different ratios of hard and soft segments to mimic alternating cartilage and ligament sections in fetal tracheas. We compared our results to that of sheep trachea. This is the first report to assess both radial rigidity and longitudinal extensibility in an engineered trachea construct. PMID- 26821339 TI - Development of vascularized iPSC derived 3D-cardiomyocyte tissues by filtration Layer-by-Layer technique and their application for pharmaceutical assays. AB - In vitro development of three-dimensional (3D) human cardiomyocyte (CM) tissues derived from human induced pluripotent stem cells (iPSCs) has long been desired in tissue regeneration and pharmaceutical assays. In particular, in vitro construction of 3D-iPSC-CM tissues with blood capillary networks have attracted much attention because blood capillaries are crucial for nutrient and oxygen supplies for CMs. Blood capillaries in 3D-iPSC-CM tissues will also be important for in vitro toxicity assay of prodrugs because of the signaling interaction between cardiomyocytes and endothelial cells. Here, we report construction of vascularized 3D-iPSC-CM tissues by a newly-discovered filtration-Layer-by-Layer (LbL) technique for cells, instead of our previous centrifugation-LbL technique. The filtration-LbL allowed us to fabricate nanometer-sized extracellular matrices (ECM), fibronectin and gelatin (FN-G), films onto iPSC-CM surfaces without any damage and with high yield, although centrifugation-LbL induced physical stress and a lower yield. The fabricated FN-G nanofilms interacted with integrin molecules on the cell membrane to construct 3D-tissues. We found that the introduction of normal human cardiac fibroblasts (NHCFs) into the iPSC-CM tissues modulated organization and synchronous beating depending on NHCF ratios. Moreover, co-culture with normal human cardiac microvascular endothelial cells (NHCMECs) successfully provided blood capillary-like networks in 3D-iPSC-CM tissues, depending on NHCF ratios. The vascularized 3D-iPSC-CM tissues indicated significantly different toxicity responses as compared to 2D-iPSC-CM cells by addition of doxorubicin as a model of a toxic drug. The constructed vascularized 3D-iPSC-CM tissues would be a promising tool for tissue regeneration and drug development. STATEMENT OF SIGNIFICANCE: In vitro fabrication of vascularized three-dimensional (3D) human cardiomyocyte (CM) tissues derived from human induced pluripotent stem cells (iPSCs) has attracted much attention owing to their requirement of much amount of nutrition and oxygen, but not yet published. In this manuscript, we report construction of vascularized 3D-iPSC-CM tissues by a newly-discovered filtration-Layer-by-Layer (LbL) technique. The filtration-LbL fabricates nanometer-sized fibronectin and gelatin (FN-G) films onto iPSC-CM surfaces. The FN-G nanofilms induce cell-cell interactions via integrin molecules on cell surfaces, leading to construction of 3D-tissues. The constructed vascularized 3D-iPSC-CM tissues would be a promising tool for tissue regeneration and drug development. We believe that this manuscript has a strong impact and offers important suggestions to researchers concerned with biomaterials and tissue engineering. PMID- 26821340 TI - High-density antimicrobial peptide coating with broad activity and low cytotoxicity against human cells. AB - Medical device-associated infections are a multi-billion dollar burden for the worldwide healthcare systems. The modification of medical devices with non leaching coatings capable of killing microorganisms on contact is one of the strategies being investigated to prevent microorganism colonization. Here we developed a robust antimicrobial coating based on the chemical immobilization of the antimicrobial peptide (AMP), cecropin-melittin (CM), on gold nanoparticles coated surfaces. The concentration of AMP immobilized (110 MUg/cm(2)) was higher than most of the studies reported so far (<10 MUg/cm(2)). This translated onto a coating with high antimicrobial activity against Gram positive and negative bacteria sp., as well as multi-drug resistant bacteria. Studies with E. coli reporter bacteria showed that these coatings induced the permeability of the outer membrane of bacteria in less than 5 min and the inner membrane in approximately 20 min. Importantly, the antimicrobial properties of the coating are maintained in the presence of 20% (v/v) human serum, and have low probability to induce bacteria resistance. We further show that coatings have low toxicity against human endothelial and fibroblast cells and is hemocompatible since it does not induce platelet and complement activation. The antimicrobial coating described here may be promising to prevent medical device-associated infections. STATEMENT OF SIGNIFICANCE: In recent years, antimicrobial peptides (AMPs) have been chemically immobilized on surfaces of medical devices to render them with antimicrobial properties. Surfaces having immobilized cationic peptides are susceptible to be adsorbed by plasma proteins with the subsequent loss of antimicrobial activity. Furthermore, with the exception of very few studies that have determined the cytotoxicity of surfaces in mammalian cells, the effect of the immobilized AMP on human cells is relatively unknown. Here we report a coating based on cecropin-melittin peptide (CM) that maintains its antimicrobial activity against Gram-positive and negative bacteria including multi-drugs resistance bacteria in the presence of serum and has relatively low cytotoxicity against human cells. The reported coatings may be translated on to variety of substrates (glass and titanium) and medical devices to prevent device-associated microbial infection. PMID- 26821341 TI - Fabrication of conductive gelatin methacrylate-polyaniline hydrogels. AB - Hydrogels with inherently conductive properties have been recently developed for tissue engineering applications, to serve as bioactive scaffolds to electrically stimulate cells and modulate their function. In this work, we have used interfacial polymerization of aniline monomers within gelatin methacrylate (GelMA) to develop a conductive hybrid composite. We demonstrate that as compared to pure GelMA, GelMA-polyaniline (GelMA-Pani) composite has similar swelling properties and compressive modulus, comparable cell adhesion and spreading responses, and superior electrical properties. Additionally, we demonstrate that GelMA-Pani composite can be printed in complex user-defined geometries using digital projection stereolithography, and will be useful in developing next generation bioelectrical interfaces. STATEMENT OF SIGNIFICANCE: We report the fabrication of a conductive hydrogel using naturally-derived gelatin methyacrylate (GelMA) and inherently conductive polyaniline (Pani). This work is significant, as GelMA-Pani composite has superior electrical properties as compared to pure Gelma, all the while maintaining biomimetic physical and biocompatible properties. Moreover, the ability to fabricate conductive-GelMA in complex user-defined micro-geometries, address the significant processing challenges associated with all inherently conductive polymers including Pani. The methodology described in this work can be extended to several conductive polymers and hydrogels, to develop new biocompatible electrically active interfaces. PMID- 26821342 TI - Spiculogenesis in the siliceous sponge Lubomirskia baicalensis studied with fluorescent staining. AB - Siliceous sponges are the most primitive multicellular animals whose skeleton consists of spicules - needle-like constructions from silicon dioxide surrounding organic axial filaments. Mechanisms of spicule formation have been intensively studied due to the high ecological importance of sponges and their interest to materials science. Light and electron microscopy are not appropriate enough to display the process from silicon-enriched cells to mature spicules because of composite structure of the sponge tissues. In this article, spiculogenesis in the siliceous sponge has been studied for the first time with the use of fluorescent microscopy. Fluorescent vital dye NBD-N2 was applied to stain growing siliceous structures in the sponge and primmorph cell system. The main stages of spicule growth in the fresh-water sponge Lubomirskia baicalensis (Pallas, 1773) were visualized: silicon accumulation in sclerocytes; formation of an organic filament protruding from the cell; further elongation of the filament and growth of the spicule in a spindle-like form with enlargement in the center; merger with new sclerocytes and formation of the mature spicule. Fluorescent microscopy combined with SEM allows us to overcome the virtual differentiation between intra- and extracellular mechanisms of spicule growth. The growing spicule can capture silicic acid from the extracellular space and merge with new silicon-enriched cells. Visualization of the growing spicules with the fluorescent dye allows us to monitor sponge viability in ecological or toxicological experiments and to apply genomic, proteomic and biochemical techniques. PMID- 26821343 TI - A detailed look at the cytoskeletal architecture of the Giardia lamblia ventral disc. AB - Giardia lamblia is a protistan parasite that infects and colonizes the small intestine of mammals. It is widespread and particularly endemic in the developing world. Here we present a detailed structural study by 3-D negative staining and cryo-electron tomography of a unique Giardia organelle, the ventral disc. The disc is composed of a regular array of microtubules and associated sheets, called microribbons that form a large spiral, held together by a myriad of mostly unknown associated proteins. In a previous study we analyzed by cryo-electron tomography the central microtubule portion (here called disc body) of the ventral disc and found a large portion of microtubule associated inner (MIPs) and outer proteins (MAPs) that render these microtubules hyper-stable. With this follow-up study we expanded our 3-D analysis to different parts of the disc such as the ventral and dorsal areas of the overlap zone, as well as the outer disc margin. There are intrinsic location-specific characteristics in the composition of microtubule-associated proteins between these regions, as well as large differences between the overall architecture of microtubules and microribbons. The lateral packing of microtubule-microribbon complexes varies substantially, and closer packing often comes with contracted lateral tethers that seem to hold the disc together. It appears that the marginal microtubule-microribbon complexes function as outer, laterally contractible lids that may help the cell to clamp onto the intestinal microvilli. Furthermore, we analyzed length, quantity, curvature and distribution between different zones of the disc, which we found to differ from previous publications. PMID- 26821344 TI - Analysis of cocaine/crack biomarkers in meconium by LC-MS. AB - Fetal exposure to illicit drugs is a worldwide problem, since many addicted women do not stop using it during pregnancy. Cocaine consumed in powdered (snorted or injected) or smoked (crack cocaine) form are harmful for the baby and its side effects are not completely known. Meconium, the first stool of a newborn, is a precious matrix usually discarded, that may contain amounts of substances consumed in the last two trimesters of pregnancy. Analyzing this biological matrix it is possible to detect the unaltered molecule of cocaine (COC) or its metabolite benzoylecgonine (BZE) and pyrolytic products anhydroecgonine methyl ester (AEME) and anhydroecgonine (AEC). A liquid chromatography mass spectrometry (LC-MS) method was validated for meconium samples after solvent extraction, followed by direct injection of 10MUL. Linearity covered a concentration range of 15 to 500ng/mg with a lower limit of quantification (LLOQ) of 15ng/mg for all analytes. Matrix effect was evaluated and showed adequate results. Detection of illicit substances usage can be crucial for the baby, since knowing that can help provide medical care as fast as possible. The method proved to be simple and fast, and was applied to 17 real meconium samples. PMID- 26821345 TI - The interaction of human serum albumin with selected lanthanide and actinide ions: Binding affinities, protein unfolding and conformational changes. AB - Human serum albumin (HSA), the most abundant soluble protein in blood plays critical roles in transportation of biomolecules and maintenance of osmotic pressure. In view of increasing applications of lanthanides- and actinides-based materials in nuclear energy, space, industries and medical applications, the risk of exposure with these metal ions is a growing concern for human health. In present study, binding interaction of actinides/lanthanides [thorium: Th(IV), uranium: U(VI), lanthanum: La(III), cerium: Ce(III) and (IV)] with HSA and its structural consequences have been investigated. Ultraviolet-visible, Fourier transform-infrared, Raman, Fluorescence and Circular dichroism spectroscopic techniques were applied to study the site of metal ions interaction, binding affinity determination and the effect of metal ions on protein unfolding and HSA conformation. Results showed that these metal ions interacted with carbonyl (CO..:)/amide(N..-H) groups and induced exposure of aromatic residues of HSA. The fluorescence analysis indicated that the actinide binding altered the microenvironment around Trp214 in the subdomain IIA. Binding affinity of U(VI) to HSA was slightly higher than that of Th(IV). Actinides and Ce(IV) altered the secondary conformation of HSA with a significant decrease of alpha-helix and an increase of beta-sheet, turn and random coil structures, indicating a partial unfolding of HSA. A correlation was observed between metal ion's ability to alter HSA conformation and protein unfolding. Both cationic effects and coordination ability of metal ions seemed to determine the consequences of their interaction with HSA. Present study improves our understanding about the protein interaction of these heavy ions and their impact on its secondary structure. In addition, binding characteristics may have important implications for the development of rational antidote for the medical management of health effects of actinides and lanthanides. PMID- 26821346 TI - Aerobic Fitness and Trainability in Healthy Youth: Gaps in Our Knowledge. AB - Peak oxygen uptake (VO2) is widely recognized as the criterion measure of young people's aerobic fitness. Peak VO2 in youth has been assessed and documented for over 75 years but the interpretation of peak VO2 and its trainability are still shrouded in controversy. Causal mechanisms and their modulation by chronological age, biological maturation and sex remain to be resolved. Furthermore, exercise of the intensity and duration required to determine peak VO2 is rarely experienced by most children and adolescents. In sport and in everyday life young people are characterized by intermittent bouts of exercise and rapid changes in exercise intensity. In this context it is the transient kinetics of pulmonary VO2 (pVO2), not peak VO2, which best describe aerobic fitness. There are few rigorously determined and appropriately analyzed data from young people's pVO2 kinetics responses to step changes in exercise intensity. Understanding of the trainability of pVO2 kinetics is principally founded on comparative studies of trained and untrained youth and much remains to be elucidated. This paper reviews peak VO2, pVO2 kinetics, and their trainability in youth. It summarizes "what we know," identifies significant gaps in our knowledge, raises relevant questions, and indicates avenues for future research. PMID- 26821347 TI - Optimized Ultrasound Conditions for Enhanced Sensitivity of Molecular Beacons in the Detection of MDR1 mRNA in Living Cells. AB - P-glycoprotein (P-gp), aprognostic indicator for chemotherapy failure, is encoded by multidrug resistance gene (MDR1). MDR1 mRNA expression could serve as a guidance for personalized medicine. However, the traditional PCR process for mRNA measurement is complicated and cannot realize the real-time detection of mRNA in living single cells. In this work, optimized gold nanoparticle-based molecular beacons were employed to determine MDR1 mRNA levels in living cancer cells. To improve detection sensitivity, ultrasound (US) irradiation was applied to facilitate and enhance cellular uptake of hairpin DNA-coated gold nanoparticle (hDAuNP). The US conditions including irradiation power, exposure time, duty cycle, and incubation time were optimized. The slight difference in MDR1 expression manipulated by siRNA silence could be recognized by US assisted hDAuNP beacons; a 10-fold increase of detection sensitivity was achieved compared with the nonultrasound assistance. Meanwhile, the detection cycle could be shortened from 12 to 2 h. Furthermore, this hDAuNP beacon can serve as an antisense agent to down-regulate P-gp expression and to reverse drug resistance of MCF-7/Adr cells to doxorubicin. Our results demonstrated that the MDR1 hDAuNP beacon assisted by US irradiation had great potential to predict chemotherapy sensitivity and to overcome multidrug resistance in cancer cells and was thus a promising tool for individualized medicine. PMID- 26821348 TI - Nanoporous aerogel as a bacteria repelling hygienic material for healthcare environment. AB - Healthcare-associated infections (HAIs) caused by pathogenic bacteria are a worldwide problem and responsible for numerous cases of morbidity and mortality. Exogenous cross-contamination is one of the main mechanisms contributing to such infections. This work investigates the potential of hydrophobically modified nanoporous silica aerogel as an antiadhesive hygienic material that can inhibit exogenous bacterial contamination. Nanoporous silica aerogels were synthesized via sol-gel polymerization of tetraethyl orthosilicate and hydrophobized using trimethylsilyl chloride. Bacterial adhesion characteristics were evaluated via dip-inoculation in suspensions of Gram-negative Escherichia coli O157:H7 and Gram positive Staphylococcus aureus. The attachment of E. coli O157:H7 and S. aureus to hydrophobic nanoporous silica aerogel (HNSA) was found to be significantly lower than that to hydrophilic and hydrophobic nonporous silica materials: 99.91% (E. coli O157:H7) and 99.93% (S. aureus) reduction in comparison to hydrophilic nonporous silica, and 82.95% (E. coli O157:H7) and 84.90% (S. aureus) reduction in comparison to hydrophobic nonporous silica. These results suggest that the use of HNSA as surfaces that come into contact with bacterial pathogens in the healthcare environment can improve bacterial hygiene, and therefore may reduce the rate of HAIs. PMID- 26821349 TI - Chromosomal aberrations and prognosis in patients with concomitant chemoradiotherapy for resected head and neck cancer. AB - Although concomitant chemoradiotherapy (CCRT) has recently become a mainstay of a primary treatment modality in advanced head and neck squamous cell carcinoma (HNSCC), some of the patients experience CCRT failure. If we can predict the CCRT outcomes, we can reduce unnecessary CCRT avoiding risk of CCRT-related complication. We aimed to identify genetic alteration markers related to treatment failure in HNSCC patients who underwent radical surgery and CCRT. Genome-wide copy number alterations (CNAs) were analyzed in 18 HNSCC patients with (n=9) or without (n=9) recurrence using oligoarray-comparative genomic hybridization and candidate CNAs were validated by quantitative RT-PCR. A total of 15 recurrently altered regions (RARs) were identified in the 18 HNSCC cases. Among them, two RARs were significantly associated with CCRT-failure: copy number gained RARs of 7p11.2 harboring EGFR (P=0.029) and 18p11.32 harboring TYMS gene (P=0.029). Three RARs (7p11.2, 9p21.3 and 18p11.32) were significantly associated with poor disease-specific survival in univariate analysis, and 7p11.2 was consistently significant in the multivariate analysis (HR 40.68, P=0.003). In conclusion, we defined novel genomic alterations associated with CCRT-failure: 7p11.2 (EGFR) and 18p11.32 (TYMS). Our results provide useful clues for the elucidation of the molecular pathogenesis of HNSCC and to predict CCRT-failure. PMID- 26821350 TI - A New Nitrogenase Mechanism Using a CFe8S9 Model: Does H2 Elimination Activate the Complex to N2 Addition to the Central Carbon Atom? AB - A truncated model of the FeMo cofactor is used to explore a new mechanism for the conversion of N2 to NH3 by the nitrogenase enzyme. After four initial protonation/reduction steps, the H4CFe8S9 cluster has two hydrogen atoms attached to sulfur, one hydrogen bridging two iron centers and one hydrogen bonded to carbon. The loss of the CH and FeHFe hydrogens as molecular hydrogen activates the cluster to addition of N2 to the carbon center. This unique step takes place at a nearly planar four-coordinate carbon center and leads to an intermediate with a significantly weakened N-N bond. A hydrogen attached to a sulfur atom is then transferred to the distal nitrogen atom. Additional prontonation/reduction steps are modeled by adding a hydrogen atom to sulfur and locating the transition states for transfer to nitrogen. The first NH3 is lost in a thermal neutral step, while the second step is endothermic. The loss of H2 activates the complex by reducing the barrier for N2 addition by 3.5 kcal/mol. Since this is the most difficult step in the mechanism, reducing the barrier for this step justifies the "extra expense" of H2 production. PMID- 26821351 TI - Targeting the mTOR Complex by Everolimus in NRAS Mutant Neuroblastoma. AB - High-risk neuroblastoma remains lethal in about 50% of patients despite multimodal treatment. Recent attempts to identify molecular targets for specific therapies have shown that Neuroblastoma RAS (NRAS) is significantly mutated in a small number of patients. However, few inhibitors for the potential treatment for NRAS mutant neuroblastoma have been investigated so far. In this in-vitro study, we show that MEK inhibitors AZD6244, MEK162 and PD0325901 block cell growth in NRAS mutant neuroblastoma cell lines but not in NRAS wild-type cell lines. Several studies show that mutant NRAS leads to PI3K pathway activation and combined inhibitors of PI3K/mTOR effectively block cell growth. However, we observed the combination of MEK inhibitors with PI3K or AKT inhibitors did not show synergestic effects on cell growth. Thus, we tested single mTOR inhibitors Everolimus and AZD8055. Interestingly, Everolimus and AZD8055 alone were sufficient to block cell growth in NRAS mutant cell lines but not in wild-type cell lines. We found that Everolimus alone induced apoptosis in NRAS mutant neuroblastoma. Furthermore, the combination of mTOR and MEK inhibitors resulted in synergistic growth inhibition. Taken together, our results show that NRAS mutant neuroblastoma can be targeted by clinically available Everolimus alone or in combination with MEK inhibitors which could impact future clinical studies. PMID- 26821353 TI - Characteristics of Honey from Serpentine Area in the Eastern Rhodopes Mt., Bulgaria. AB - Honey samples collected during 2007-2010 from serpentine and non-serpentine localities in the Eastern Rhodopes Mt. (Bulgaria) were characterized on the basis of their pollen content by qualitative melissopalynological analysis and physicochemical composition. Water content, pH, electrical conductivity, macroelements-K, Ca, Mg, P, and microelements-As, Cd, Co, Cr, Cu, Fe, Mn, Na, Ni, Pb, and Zn were determined after the Harmonised Methods of the International Honey Commission and ICP-AES method. The results from serpentine honey samples were compared with data from bee pollen collected from the same serpentine area. Different elements have different concentrations in honey from the same botanical type even collected from the same geographical region, same locality, and same beehive but in different vegetation season. The elements Mg, Mn, Ni, and P contribute mostly for separation of the serpentine honey samples based on measured elemental concentrations and performed principal component analysis. The element concentrations were higher in bee pollen and above the permissible limits for the toxic metals Cd and Pb. No specific indicator plant species was found for identification of the geographical origin of serpentine honey in relation to the forage of bees. PMID- 26821352 TI - Pilot Study on the Influence of Nutritional Counselling and Implant Therapy on the Nutritional Status in Dentally Compromised Patients. AB - OBJECTIVES: To investigate the impact of implant-prosthetic rehabilitation combined with nutritional counseling on the nutritional status of patients with severely reduced dentitions. DESIGN: An explorative intervention study including an intra-individual comparison of 20 patients with severely reduced dentitions in terms of nutrition- and quality of life-related parameters recorded at baseline and at six and twelve months after implant-prosthetic rehabilitation. PARTICIPANTS: Twenty patients from the Department of Prosthetic Dentistry of Justus-Liebig University of Giessen, with an mean age of 63 years, who had fewer than ten pairs of antagonists. MEASUREMENTS: The baseline data collection included dental status, a chewing ability test, laboratory parameters, anthropometric data (body mass index), energy supply, a 3-day dietary record, an analysis of the oral health-related quality of life (OHRQoL) with the OHIP-G14, the Mini-Mental Status (MMS) and Mini Nutritional Assessment (MNA). Six months after implantation and prosthetic rehabilitation, individual nutritional counseling was performed by a dietician. Data were again collected and analyzed. A final follow-up was conducted 12 months after prosthetic rehabilitation. RESULTS: Despite the highly significant improvement in masticatory ability and OHRQoL after implant-prosthetic rehabilitation, no significant changes were observed regarding MNA, anthropometric data or energy supply. Except for cholinesterase (p = 0.012), ferritin (p = 0.003), folic acid (p = 0.019) and vitamin A (p = 0.004), no laboratory parameter changed significantly during the investigation period. In addition, no general significant differences were observed for nutrient intake or food choice. CONCLUSION: The present study does not confirm the assumption that the implant-prosthetic rehabilitation of patients with severely reduced residual dentitions with or without an individual nutritional counseling influences nutritional status. PMID- 26821354 TI - Preliminary Study to Test the Feasibility of Sex Identification of Human (Homo sapiens) Bones Based on Differences in Elemental Profiles Determined by Handheld X-ray Fluorescence. AB - Sex assignment of human remains is a crucial step in forensic anthropological studies. The aim of this study was to examine elemental differences between male and female bones using X-ray fluorescence (XRF) and determine if elemental profiling could be used for sex discrimination. Cranium, humerus, and os coxae of 60 skeletons (30 male, 30 female) from the Chiang Mai University Skeletal Collection were scanned by XRF and differences in elemental profiles between male and female bones determined using discriminant analysis. In the cranium, three elements (S, Ca, Pb) were significantly higher in males and five elements (Si, Mn, Fe, Zn, Ag) plus light elements (atomic number lower than 12) were higher in females. In humerus and os coxae, nine elements were significantly higher in male and one element was higher in female samples. The accuracy rate for sex estimation was 60, 63, and 61 % for cranium, humerus, and os coxae, respectively, and 67 % when data for all three bones were combined. We conclude that there are sex differences in bone elemental profiles; however, the accuracy of XRF analyses for discriminating between male and female samples was low compared to standard morphometric and molecular methods. XRF could be used on small samples that cannot be sexed by traditional morphological methods, but more work is needed to increase the power of this technique for gender assignment. PMID- 26821355 TI - Investigation of biofilm formation ability, antimicrobial resistance and the staphylococcal cassette chromosome mec patterns of methicillin resistant Staphylococcus epidermidis with different sequence types isolated from children. AB - This study investigated the molecular characterizations of 80 methicillin resistant Staphylococcus epidermidis (MRSE) collected during 2012-2013 in Tehran Children's Medical Center, Iran. About 90% of MRSE isolates were multi-drug resistant (MDR) and the highest resistance was observed to cotrimoxazole and they were quite sensitive to quinupristin-dalfopristin and linezolid. Though vanA gene was not detected, the majority of isolates showed intermediate resistance to vancomycin (MIC90 16 MUg/ml). Resistance to mupirocin was observed in 18 isolates. Staphylococcal cassette chromosome mec (SCCmec) types V, III, IV and II were detected in 23.75%, 7.5%, 6.25% and 5% of isolates respectively, in some of which the additional parts of mec or ccr complexes were observed. In 57.5% MRSE isolates SCCmec types were not classified. 41.2% of MRSE isolates were carrying intercellular adhesion (ica) operon and 40% had strong or intermediate biofilm. The types of arginine catabolic mobile element (ACME) were limited to type I and II. Nine sequence types (STs) were seen in mupirocin resistant MRSE isolates. The common STs were ST2, ST5 and ST22 with 27.7% (5/18), 22.2% (4/18) and 16.6% (3/18) frequencies, respectively. ST23, ST54 and ST179 plus three novels STs 580, 581,588 were also observed. The majority of STs, 83.3% (15/18) belonged to clonal complex 2 (CC2). The spread of antibiotic resistance and virulence factors among MRSE species is an alarming sign in Children's Hospitals. The combination of these two issues leads to increase the chance of successfully establishing of common STs in hospital environments, and promotes the device-related infections and bacteremia. PMID- 26821356 TI - Influence of Melaleuca alternifolia oil nanoparticles on aspects of Pseudomonas aeruginosa biofilm. AB - The Pseudomonas aeruginosa is a gram-negative bacillus and frequent cause of infection. This microorganism is resistant intrinsically to various drugs. The P. aeruginosa is associated with the biofilm formation, which causes worsen the prognosis and difficulty the treatment. The influence of Melaleuca alternifolia oil or "tree of tee" oil (TTO) and TTO nanoparticles on adhesion of P. aeruginosa in buccal epithelial cells was investigated. Also was determined the antimicrobial and antibiofilm activity against this microorganism. The TTO nanoparticles were produced by deposition of preformed polymer and the physic chemical properties of nanoparticles were measured by electrophoresis and dynamic light scattering. The characterization of nanoparticle showed acceptable values for diameter and zeta potential. The evaluation of antimicrobial and antibiofilm activity against P. aeruginosa PAO1 was performed by microdilution indicating the minimal inhibitory concentration, and the potential antibiofilm. It was verified the action on virulence factors such the motility, besides the influence on adhesion in buccal epithelial cells. Both oil and nanoparticles showed a decrease in adhesion of microorganisms to buccal cells, decrease of biofilm and interfering on P. aeruginosa PAO1 motility. The nanostructuration of TTO, shows be a viable alternative against formed biofilm microorganisms. PMID- 26821357 TI - Differential expression of CXCR4 and CXCR7 with various stem cell markers in paired human primary and recurrent glioblastomas. AB - The chemokine CXCL12 (also termed SDF-1, stromal cell-derived factor-1) and its receptors CXCR4 and CXCR7 are known to play a pivotal role in tumor progression including glioblastomas (GBM). Previous investigations focused on the expression and functional roles of CXCR4 and CXCR7 in different GBM cell subpopulations, but comparative analysis in matched primary versus recurrent GBM samples are still lacking. Thus, here we investigated the expression of CXCR4 and CXCR7 on mRNA and protein level using matched primary and recurrent GBM pairs. Additionally, as GBM CXCR4-positive stem-like cells are supposed to give rise to recurrence, we compared the expression of both receptors in primary and recurrent GBM cells expressing either neural (MUSASHI-1) or embryonic stem cell markers (KLF-4, OCT 4, SOX-2, NANOG). We were able to show that both CXCR4 and CXCR7 were expressed at considerable mRNA and protein levels. CXCR7 was downregulated in relapse cases, and different groups regarding CXCR4/CXCR7 expression differences between primary and recurrent samples could be distinguished. A co-expression of both receptors was rare. In line with this, CXCR4 was co-expressed with all investigated neural and embryonic stem cell markers in both primary and recurrent tissues, whereas CXCR7 was mostly found on stem cell marker-negative cells, but was co-expressed with KLF-4 on a distinct GBM cell subpopulation. These results point to an individual role of CXCR4 and CXCR7 in stem cell marker-positive GBM cells in glioma progression and underline the opportunity to develop new therapeutic tools for GBM intervention. PMID- 26821358 TI - Reproductive disorders among cosmetologists and hairdressers: a meta-analysis. AB - PURPOSE: Occupational risks for reproductive disorders among hairdressers and cosmetologists have been examined in numerous epidemiological studies, although the results of those studies have been inconsistent. Therefore, we conducted a meta-analysis of published studies to evaluate the risks of reproductive disorders among cosmetologists and hairdressers. METHODS: We searched the MEDLINE, EMBASE, and Cochrane Library databases, as well as the reference lists of relevant publications, to identify studies for our analysis. After careful consideration, 19 eligible studies were included in the meta-analysis. We also performed systematic evaluations of publication bias, heterogeneity, and publication quality. RESULTS: Study-specific odds ratios (ORs) were weighted using the inverse of their variance to calculate fixed- and random-effect pooled estimates. The meta-analysis revealed a significantly increased risk of infertility (OR 1.15, 95 % CI 1.03-1.28), fetal death (OR 1.14, 95 % CI 1.04 1.24), and preterm delivery (OR 1.04, 95 % CI 1.00-1.07) among hairdressers and cosmetologists. CONCLUSION: These findings indicate that hairdressers and cosmetologists have a higher risk of reproductive disorders, compared to the general population. PMID- 26821360 TI - Not Surprising: Patients Not Engaged and Not Using Public Healthcare Quality Information. PMID- 26821359 TI - Patient, Caregiver, and Nurse Preferences for Treatments for Bone Metastases from Solid Tumors. AB - BACKGROUND: Bone-targeted agents (BTAs) used for the prevention of skeletal related events (SREs) associated with metastatic bone disease possess different attributes that factor into treatment decisions. OBJECTIVE: The aim of this study was to evaluate preferences of patients, caregivers, and nurses for features of BTAs used to prevent SREs in patients with a self-reported physician diagnosis of bone metastasis from solid tumors. METHODS: Patients (n = 187), primary caregivers (n = 197), or nurses (n = 196) completed a web-enabled discrete-choice experiment (10-question survey) in which they chose between pairs of hypothetical profiles of BTAs. Each profile was defined by six key treatment attributes, including efficacy and safety (two each) and route/frequency of administration and cost (one each). The relative importance of treatment attributes and levels was estimated. RESULTS: The most important treatment attribute for patients and nurses was out-of-pocket cost, and for caregivers, treatment-related risk of renal impairment. Risk of renal impairment was the second most important attribute for patients and nurses, while time until first SRE was the third most important attribute for all respondents. For nurses, risk of osteonecrosis of the jaw was least important, and for patients and caregivers, mode of administration was least important. LIMITATIONS: Respondents considered hypothetical medications; therefore, their decisions may not have the same consequences as actual decisions. CONCLUSIONS: The perspectives of patients, caregivers, and nurses are integral when making treatment decisions about BTAs to prevent SREs associated with solid tumors. Identifying the relative importance of attributes of BTAs will aid in the proper selection of therapy in this setting, which may improve patient outcomes. PMID- 26821361 TI - Characterizing Molecular Mechanisms of Imidacloprid Resistance in Select Populations of Leptinotarsa decemlineata in the Central Sands Region of Wisconsin. AB - The Colorado potato beetle, Leptinotarsa decemlineata (Say), is a major agricultural pest in the Central Sands region of Wisconsin. Imidacloprid, a neonicotinoid insecticide, has commonly been used for control of L. decemlineata since its registration in 1995. In the last 10 years, many field populations of L. decemlineata have begun to show increasing imidacloprid resistance. We studied resistance phenotype as a phenomenon that reduces neonicotinoid efficacy and has practical consequences for potato pest management. Although we have not observed complete field failure following the use of these products, multiple studies have demonstrated that the lethal concentration to kill 50% of the test organisms (LC50) in different field populations of L. decemlineata varies greatly which may suggest that resistance of L. decemlineata is heritable and involves genetic changes. An important challenge in understanding resistance is assessing the genetic mechanisms associated with resistance and classifying up-regulated genes that may be involved in combating an insecticide insult. In this study we uncovered trends in imidacloprid phenotypic response that have developed in the region by estimating the LC50 values among different field populations against a range of imidacloprid doses. The LC50 values collected in 2008-2011, and more recently in 2013 and 2014, show that some field locations remain susceptible to imidacloprid, while nearby fields (<100km) have developed high levels of resistance. We also sought to uncover potential mechanisms of resistance at each field location. We compiled a transcriptome for populations, characterized as phenotypically 'susceptible' and 'resistant', by isolating mRNA from adult beetles and analyzing gene expression level differences. Strong differences were observed in constituently up and down-regulated genes among different field populations. Most significantly, the up-regulation of 3 cytochrome p450s and a glutathione synthetase related protein in multiple resistant populations provide a mechanistic explanation of resistance evolution in L. decemlineata. PMID- 26821362 TI - Helicobacter pylori infection is high in paediatric nonulcer dyspepsia but not associated with specific gastrointestinal symptoms. AB - AIM: The association between Helicobacter pylori infection and gastrointestinal symptoms is debatable in childhood. We examined the potential relationship between H. pylori infection and gastrointestinal symptoms in Brazilian children with nonulcer dyspepsia. METHODS: This prospective observational study analysed 240 Brazilian children and adolescents (68.7% girls) with chronic nonulcer dyspepsia, who underwent upper gastrointestinal endoscopy and biopsy. Their mean age was 9.8 years (range 4-17). Upper gastrointestinal symptoms, including abdominal pain, nausea, burning, early satiety, belching and weigh loss, were evaluated by a questionnaire and H. pylori infection was determined by histopathology of gastric biopsies. RESULTS: H. pylori infection was identified in 123/240 patients (52%). There was no significant association between the H. pylori infection and gastrointestinal symptoms and no relationship between the infection and abdominal pain or pain characteristics. However, nausea was significantly associated with the H. pylori infection, with an odds ratio of 1.76 and 95% confidence interval of 1.1-2.94 p < 0.03. Symptoms lasting longer than 12 months were significantly more frequent in children with pangastritis than in those with antral gastritis (p < 0.05). CONCLUSION: The prevalence of H. pylori infection was high in Brazilian children with nonulcer dyspepsia, but was not associated with specific signs and symptoms, except for nausea. PMID- 26821363 TI - Systematic approaches to identify functional lncRNAs. AB - Long noncoding RNAs (lncRNAs) were discovered in eukaryotes more than 30 years ago [1]. Recent advances in genomics have led to the discovery that lncRNAs are transcribed pervasively across the genome [2(*),3,4,5(*)]. There are an increasing number of reports that identify lncRNAs whose expression is modulated during cell differentiation or in disease states. However, biological functions for the vast majority of them are yet to be determined. Here, we propose two ways to identify lncRNAs that have biological functions: to identify lncRNAs with dedicated preinitiation complexes (PICs), and to focus on those whose transcription is highly regulated. PMID- 26821365 TI - Gene regulation and chromatin organization: relevance of cohesin mutations to human disease. AB - Consistent with the diverse roles of the cohesin complex in chromosome biology, mutations in genes encoding cohesin and its regulators are found in different types of cancer and in developmental disorders such as Cornelia de Lange Syndrome. It is so far considered that the defects caused by these mutations result from altered function of cohesin in regulating gene expression during development. Chromatin conformation analyses have established the importance of cohesin for the architecture of developmental gene clusters and in vivo studies in mouse and zebrafish demonstrated how cohesin defects lead to gene misregulation and to malformations similar to the related human syndromes. Here we present our current knowledge on cohesin's involvement in gene expression, highlighting molecular and mechanistic consequences of pathogenic mutations in the Cornelia de Lange syndrome. PMID- 26821366 TI - Differential Effects of Roads and Traffic on Space Use and Movements of Native Forest-Dependent and Introduced Edge-Tolerant Species. AB - Anthropogenic infrastructure such as roads and non-native species are major causes of species endangerment. Understanding animal behavioral responses to roads and traffic provides insight into causes and mechanisms of effects of linear development on wildlife and aids effective mitigation and conservation. We investigated effects of roads and traffic on space use and movements of two forest-dwelling species: endemic, forest-dependent Mount Graham red squirrels (Tamiasciurus hudsonicus grahamensis) and introduced, edge-tolerant Abert's squirrels (Sciurus aberti). To assess the effects of roads on space use and movement patterns, we compared the probability that a squirrel home range included roads and random lines in forests, and assessed effects of traffic intensity on rate of road crossing and movement patterns. Red squirrels avoided areas adjacent to roads and rarely crossed roads. In contrast, Abert's squirrels were more likely to include roads in their home ranges compared to random lines in forests. Both red squirrels and Abert's squirrels increased speed when crossing roads, compared to before and after road crossings. Increased hourly traffic volume reduced the rate of road crossings by both species. Behavioral responses of red squirrels to roads and traffic resemble responses to elevated predation risk, including reduced speed near roads and increased tortuosity of movement paths with increased traffic volume. In contrast, Abert's squirrels appeared little affected by roads and traffic with tortuosity of movement paths reduced as distance to roads decreased. We found that species with similar body size category (<1 kg) but different habitat preference and foraging strategy responded to roads differently and demonstrated that behavior and ecology are important when considering effects of roads on wildlife. Our results indicate that roads restricted movements and space use of a native forest-dependent species while creating habitat preferred by an introduced, edge-tolerant species. PMID- 26821364 TI - Hide and seek: how chromatin-based pathways silence retroelements in the mammalian germline. AB - Retroelements comprise a major fraction of most mammalian genomes. To protect their fitness and stability, hosts must keep retroelements in check in their germline. In most tissues mobile element insertions are decorated with chromatin modifications suggestive of transcriptional silencing. However, germline cells undergo massive chromatin reprogramming events, which erase repressive chromatin marks and necessitate de novo re-establishment of silencing. How do host genomes achieve the discrimination necessary for this de novo silencing? A series of recent studies have revealed aspects of the multi-pronged strategy that mammalian genomes use to identify and silence retroelements. These strategies include the use of small RNA-guides, of specialized DNA-binding protein adaptors and of proteins that repair chromatin discontinuities caused by retroelement insertions. Genetic analyses reveal the importance of these mechanisms of protection, each of which specializes in silencing retroelements of different evolutionary ages. Together, these strategies allow mammalian genomes to withstand the high burden of their parasites. PMID- 26821367 TI - Effects of autophagy regulation of tumor-associated macrophages on radiosensitivity of colorectal cancer cells. AB - Tumor-associated macrophages (TAMs), a major component of the tumor microenvironment, are crucial to the processes of tumor growth, infiltration and metastasis, and contribute to drug resistance. The importance of TAMs in radiation resistance of colorectal cancer remains unclear. To investigate the effects of autophagy regulation of TAMs on the radiosensitivity of colorectal cancer cells, the current study induced TAM formation from THP-1 monocyte cells. Sequential treatment of THP-1 cells with PMA for 72 h and human recombinant interleukin-4 for 24 h was used to stimulate THP-1 differentiation to TAMs. Expression of the cell surface markers CD68, CD204 and CD206, and changes to cell morphology were used to confirm successful differentiation. The TAMs were stimulated to promote or inhibit autophagy during co-culture with LoVo colorectal adenocarcinoma cells. The cells were irradiated, with subsequent measurement of LoVo colony formation and apoptosis. Additionally, the expression of p53, Bcl-2, survivin and Smac proteins was assessed by western blotting. Monodansylcadaverin staining was used to analyze the presence of autophagic vacuoles in TAM, and western blot analysis was used to assess the expression of Beclin-1, LC3B I and II, ATG-3, -5 and -7. The results demonstrated TAM autophagy to be markedly altered by rapamycin and bafilomycin A1 treatment. Following co-culture with TAMs, the colony formation rate and survival fraction of LoVo cells were significantly higher than those in the control group (P<0.05). It was further demonstrated that the regulation of autophagy in TAMs was able to inhibit the colony formation of LoVo colorectal cancer cells. Upregulation of TAM autophagy using rapamycin exhibited more effective inhibition of LoVo colony formation than autophagy downregulation. Notably, apoptosis was significantly increased in LoVo cells when co-cultured with TAMs only, or with rapamycin-mediated autophagy upregulated TAMs, compared with LoVo cells cultured alone (P<0.01). Expression of Bcl-2, survivin and p53 were reduced in LoVo cells co-cultured with TAMs, compared with the control group (P<0.05), whereas Smac expression was increased in the co-culture groups (P<0.01). It was demonstrated that rapamycin-mediated autophagy stimulation in TAMs led to reduced expression levels of survivin and Bcl-2, however, Smac expression was increased. The upregulation of autophagy in TAMs inhibited proliferation and induced apoptosis in colon cancer cells, and altered the expression of radiosensitivity-associated proteins. This data indicated that the radiosensitivity of colorectal cancer cells is associated with autophagy of TAM, and that stimulating TAM autophagy may increase the radiosensitivity of colorectal cancer cells. PMID- 26821368 TI - Pleural fluid procalcitonin to distinguish infectious from noninfectious etiologies of pleural effusions. AB - In this study we investigate the diagnostic value of pleural fluid procalcitonin (PCT) in distinguishing infectious and noninfectious etiologies of pleural effusion. We reviewed the medical records of 75 hospitalized patients who underwent thoracentesis between 2011 and 2012. Data on pleural fluid lactate dehydrogenase (LDH), protein, albumin, cell count and differential, pH, Gram stain and culture, cytology, triglyceride, cholesterol, amylase, and PCT were collected. Data on serum LDH, protein, albumin, prothrombin time, normalized, and blood culture were also collected. Pleural effusions were classified into 2 groups, infectious and noninfectious. There were 18 infectious pleural effusions (IPE) and 57 noninfectious pleural effusions (NIPE). Median pleural fluid PCT was 1.088 ng/mL (0.312-2.940 ng/mL) in IPE and 0.123 ng/mL (0.05-0.263 ng/mL) in NIPE, with a P value < 0.0001. Pleural fluid PCT > 0.25 ng/mL had a sensitivity of 77.78% and specificity of 74.14% for diagnosing an IPE. A subgroup analysis of PCT in exudative infectious effusions versus exudative noninfectious malignant/paramalignant effusions showed higher levels in the former. PCT is a novel biomarker for diagnosing infectious pleural effusion, and it would be worthwhile to investigate the role of pleural PCT in assessing severity of illness, risk stratification, and antibiotic stewardship in hospitalized patients with pleural effusions. Journal of Hospital Medicine 2016;11:363-365. 2016 Society of Hospital Medicine. PMID- 26821369 TI - Increases in Acute Hepatitis B Virus Infections - Kentucky, Tennessee, and West Virginia, 2006-2013. AB - As many as 2.2 million persons in the United States are chronically infected with hepatitis B virus (HBV) (1), and approximately 15%-25% of persons with chronic HBV infection will die prematurely from cirrhosis or liver cancer (2). Since 2006, the overall U.S. incidence of acute HBV infection has remained stable; the rate in 2013 was 1.0 case per 100,000 persons (3). Hepatitis B vaccination is highly effective in preventing HBV infection and is recommended for all infants (beginning at birth), all adolescents, and adults at risk for HBV infection (e.g., persons who inject drugs, men who have sexual contact with men, persons infected with human immunodeficiency virus [HIV], and others). Hepatitis B vaccination coverage is low among adults: 2013 National Health Interview Survey data indicated that coverage with >=3 doses of hepatitis B vaccine was 32.6% for adults aged 19-49 years (4). Injection drug use is a risk factor for both hepatitis C virus (HCV) and HBV. Among young adults in some rural U.S. communities, an increased incidence of HCV infection has been associated with a concurrent increase of injection drug use (5); and recent data indicate an increase of acute HCV infection in the Appalachian region associated with injection drug use (6). Using data from the National Notifiable Diseases Surveillance System (NNDSS) during 2006-2013, CDC assessed the incidence of acute HBV infection in three of the four Appalachian states (Kentucky, Tennessee, and West Virginia) included in the HCV infection study (6). Similar to the increase of HCV infections recently reported, an increase in incident cases of acute HBV infection in these three states has occurred among non-Hispanic whites (whites) aged 30-39 years who reported injection drug use as a common risk factor. Since 2009, cases of acute HBV infection have been reported from more non-urban than urban regions. Evidence-based services to prevent HBV infection are needed. PMID- 26821370 TI - [Respiratory syncytial virus (RSV) infections in the pediatric teaching hospital Charles de Gaulle of Ouagadougou, Burkina Faso]. AB - Human respiratory syncytial virus (RSV) infections are little known in Burkina Faso. The objective of our work is to study the epidemiological and clinical aspects of RSV infections in infants in the Pediatric Teaching Hospital Charles de Gaulle of Ouagadougou. Between July 1(st) 2010 and June 30(th) 2011, we analyzed by direct immunofluorescence and PCR nasopharyngeal swabs from children from 0 to 36 months old. All in all, 210 patients among whom 74 from the external consultation (35.2%) and 136 hospitalized (64.7%) benefited from a nasopharyngeal aspiration. The motives for consultation were cough (91.7%), rhinitis (79.2%), fever (79.2%) and respiratory distress syndrome (66.7%). The evoked diagnoses were predominantly the acute bronchiolitis in 14 cases (58.3%) followed by the acute pulmonary disease in 7 patients (26.2%) then flue in 1 patient (16.7%). We detected by direct immunofluorescence the antigens of the respiratory viruses in 21 nasopharyngeal aspirations with 10 cases of respiratory syncytial virus (RSV) infections (47.6%). The PCR realized on 208 samples allowed to identify 153 positive samples (73.2%) with 24 RSV, i.e. a global prevalence of 16.1% with a peak of 18 cases (75%). In October, all the patients benefited from an often multiple antibiotic treatment of at least 10 days which was not still necessary. The evolution was favorable for all patients. This study confirms the important place of the viruses which are detected in 70% of the cases. The PCR multiplex, certainly expensive but effective and successful, deserves to be used in our developing countries to avoid the irrational prescription of antibiotic. PMID- 26821371 TI - [Assessment of mother-to-child HBV transmission at the prenatal consultation in Vientiane, Laos]. AB - Chronic infection with hepatitis B virus (HBV) remains highly endemic in Laos, mainly related to mother to child transmission. Despite the introduction of the vaccination against HBV in the Expanded Programme on Immunization in 2001 and the administration of a vaccine birth dose as part of a 3-dose schedule since 2004, infant immunization coverage remains inadequate because most mothers are not aware of the risks. A survey was conducted in early 2013 in Vientiane capital among women who undergo serologic screening for hepatitis B at the prenatal consultation, to assess their knowledge and risk factors of HBV infection. It included the administration of a standardized questionnaire divided into four parts (socio-demographic data, knowledge about hepatitis B, risk factors and immunization status) and a screening test for the HBV surface antigen (HBsAg). A total of 200 pregnant women were recruited consecutively in Mahosot hospital. They were aged 14-39 years (mean 27 +/- 4.76 years), civil servants (37%) or housewives (33.5%) with a secondary or higher education level (80%). Most were multiparous (68.5%) and attended antenatal care in the third trimester of pregnancy (61%). Sixteen (8%) tested HBsAg positive. The HBsAg seroprevalence was higher in the 26-30 years age group, among women above the primary school education level and women practicing the profession of shopkeeper or civil servant, but these differences were not significant. Hepatitis B was known by a small majority (53%) but 26% could name the routes of transmission, 28% considered it as a serious illness and 24.5% were aware of the HBV vaccine. No risk factor for blood or sexual exposure to HBVinfection was significantly linked to the HBsAg carriage. In this sample of pregnant women mostly urban, educated and multiparous with access to a central hospital, the high rate of HBV infection and the low level of knowledge about the risk of mother-to-child HBV transmission reveals a major gap in information and advice that should be provided during prenatal visits. A large scale program of health education focused on the prevention of vertical transmission of HBV should be implemented, parallel to the extension of HBV vaccine coverage including a birth dose for the Lao children. PMID- 26821372 TI - Who uses pharmacy for flu vaccinations? Population profiling through a UK pharmacy chain. AB - BACKGROUND: There is a need to increase influenza vaccination rates in England particularly among those who are under 65 years of age and at-risk because of other conditions and treatments. OBJECTIVE: To understand the profile of people accessing flu vaccination services within a large pharmacy chain. METHOD: Pharmacists requested people who had been vaccinated in 2014/15 to complete a questionnaire. Data was captured electronically on vaccine delivery levels across 1201 pharmacies. Deprivation profiles were calculated using the Carstairs index. RESULTS: 1741 patients from a total of 55 pharmacies completed the survey. Convenience and accessibility remain the key reasons for attending pharmacy. Pharmacy services are accessed by people from all postcode areas, including some from the most deprived localities. CONCLUSION: Pharmacy flu vaccination services complement those provided by general practitioners to help improve overall coverage and vaccination rates for patients in at-risk groups. These services are highly accessed by patients from all socio demographic areas, and seem to be particularly attractive to carers, frontline healthcare workers, and those of working age. PMID- 26821373 TI - Distribution of tetrodotoxin in the ribbon worm Lineus alborostratus (Takakura, 1898) (nemertea): Immunoelectron and immunofluorescence studies. AB - Transmission electron and confocal laser scanning (CLSM) microscopies with monoclonal anti-tetrodotoxin antibodies were used to locate tetrodotoxin (TTX) in tissues and gland cells of the ribbon worm Lineus alborostratus. CLSM studies have shown that the toxin is primarily localized in the cutis (special subepidermal layer) of the body wall and in the glandular epithelium of the proboscis. Immunoelectron micrographs have shown that only subepidermal bacillary gland cells type I in cutis and pseudocnidae-containing and mucoid gland cells manifested TTX-gold labeling. TTX was associated with the nuclear envelope, endoplasmic reticulum membrane, and secretory granules of TTX-positive gland cells. These studies indicate that TTX is brought into the cytoplasm of the glandular cells of the cutis and proboscis epithelium, where it is associated with membrane-enclosed organelles involved in protein secretion and then concentrated in glandular granules. PMID- 26821374 TI - PDGF-B/PDGFR-beta Signaling: A New Potential Therapeutic Target of Atrial Fibrillation. PMID- 26821375 TI - [Not Available]. PMID- 26821376 TI - Effectiveness of cardiac surgery in patients with trisomy 18: a single institutional experience. AB - BACKGROUND: Surgical repair for cardiac lesions has rarely been offered to patients with trisomy 18 because of their very short lifespans. We investigated the effectiveness of cardiac surgery in patients with trisomy 18. Patients and methods We performed a retrospective analysis of 20 consecutive patients with trisomy 18 and congenital cardiac anomalies who were evaluated between August, 2003 and July, 2013. All patients developed respiratory or cardiac failure due to excessive pulmonary blood flow. Patients were divided into two subgroups: one treated surgically (surgical group, n=10) and one treated without surgery (conservative group, n=10), primarily to compare the duration of survival between the groups. RESULTS: All the patients in the surgical group underwent cardiac surgery with pulmonary artery banding, including patent ductus arteriosus ligation in nine patients and coarctation repair in one. The duration of survival was significantly longer in the surgical group than in the conservative group (495.4+/-512.6 versus 93.1+/-76.2 days, respectively; p=0.03). A Cox proportional hazard model found cardiac surgery to be a significant predictor of survival time (risk ratio of 0.12, 95% confidence interval 0.016-0.63; p=0.01). CONCLUSIONS: Cardiac surgery was effective in prolonging survival by managing high pulmonary blood flow; however, the indication for surgery should be carefully considered on a case-by-case basis, because the risk of sudden death remains even after surgery. Patients' families should be provided with sufficient information to make decisions that will optimise the quality of life for both patients and their families. PMID- 26821377 TI - Antibiotic induced bacterial lysis provides a reservoir of persisters. AB - In a genetically uniform bacterial population a small subset of antibiotic susceptible cells enter an antibiotic tolerant state and are hence referred to as persisters. These have been proposed to be rare phenotypic variants with several stochastically activated independent parallel processes. Here we show an overlooked phenomenon, bacterial tolerance of extraordinary high levels of ampicillin due to encasement of viable cells by an antibiotic induced network of cell debris. This matrix shields the entrapped cells from contact with the bacteriolytic beta-lactam antibiotic ampicillin and may be an underlying cause of notable variations in the level of ampicillin tolerant persisters as well as of considerable medical significance. Disruption of the matrix leads to the rapid elimination of hidden survivors, revealing their metabolically active state. PMID- 26821378 TI - Characterization of genes encoding proteins containing HD-related output domain in Xanthomonas campestris pv. campestris. AB - The Gram-negative plant pathogen Xanthomonas campestris pv. campestris (Xcc) is the causative agent of black rot in crucifers. The production of Xcc virulence factors is regulated by Clp and RpfF. HD-related output domain (HDOD) is a protein domain of unknown biochemical function. The genome of Xcc encodes three proteins (GsmR, HdpA, and HdpB) with an HDOD. The GsmR has been reported to play a role in the general stress response and cell motility and its expression is positively regulated by Clp. Here, the function and transcription of hdpA and hdpB were characterized. Mutation of hdpA resulted in enhanced bacterial attachment. In addition, the expression of hdpA was positively regulated by RpfF but not by Clp, subject to catabolite repression and affected by several stress conditions. However, mutational analysis and reporter assay showed that hdpB had no effect on the production of a range of virulence factors and its expression was independent of Clp and RpfF. The results shown here not only extend the previous work on RpfF regulation to show that it influences the expression of hdpA in Xcc, but also expand knowledge of the function of the HDOD containing proteins in bacteria. PMID- 26821379 TI - High-Resolution Underwater Mapping Using Side-Scan Sonar. AB - The goal of this study is to generate high-resolution sea floor maps using a Side Scan Sonar(SSS). This is achieved by explicitly taking into account the SSS operation as follows. First, the raw sensor data is corrected by means of a physics-based SSS model. Second, the data is projected to the sea-floor. The errors involved in this projection are thoroughfully analysed. Third, a probabilistic SSS model is defined and used to estimate the probability of each sea-floor region to be observed. This probabilistic information is then used to weight the contribution of each SSS measurement to the map. Because of these models, arbitrary map resolutions can be achieved, even beyond the sensor resolution. Finally, a geometric map building method is presented and combined with the probabilistic approach. The resulting map is composed of two layers. The echo intensity layer holds the most likely echo intensities at each point in the sea-floor. The probabilistic layer contains information about how confident can the user or the higher control layers be about the echo intensity layer data. Experimental results have been conducted in a large subsea region. PMID- 26821380 TI - Glycine and Folate Ameliorate Models of Congenital Sideroblastic Anemia. AB - Sideroblastic anemias are acquired or inherited anemias that result in a decreased ability to synthesize hemoglobin in red blood cells and result in the presence of iron deposits in the mitochondria of red blood cell precursors. A common subtype of congenital sideroblastic anemia is due to autosomal recessive mutations in the SLC25A38 gene. The current treatment for SLC25A38 congenital sideroblastic anemia is chronic blood transfusion coupled with iron chelation. The function of SLC25A38 is not known. Here we report that the SLC25A38 protein, and its yeast homolog Hem25, are mitochondrial glycine transporters required for the initiation of heme synthesis. To do so, we took advantage of the fact that mitochondrial glycine has several roles beyond the synthesis of heme, including the synthesis of folate derivatives through the glycine cleavage system. The data were consistent with Hem25 not being the sole mitochondrial glycine importer, and we identify a second SLC25 family member Ymc1, as a potential secondary mitochondrial glycine importer. Based on these findings, we observed that high levels of exogenous glycine, or 5-aminolevulinic acid (5-Ala) a metabolite downstream of Hem25 in heme biosynthetic pathway, were able to restore heme levels to normal in yeast cells lacking Hem25 function. While neither glycine nor 5-Ala could ameliorate SLC25A38 congenital sideroblastic anemia in a zebrafish model, we determined that the addition of folate with glycine was able to restore hemoglobin levels. This difference is likely due to the fact that yeast can synthesize folate, whereas in zebrafish folate is an essential vitamin that must be obtained exogenously. Given the tolerability of glycine and folate in humans, this study points to a potential novel treatment for SLC25A38 congenital sideroblastic anemia. PMID- 26821383 TI - Role of the Wnt/beta-catenin signaling pathway in the response of chondrocytes to mechanical loading. AB - In order to better understand the mechanisms by which chondrocytes respond to mechanical stimulation, ATDC5 mouse embryonic carcinoma cells were induced to differentiate into chondrocytes and then exposed to mechanical loading. To specifically elucidate the role of this pathway, the localization and expression of proteins involved in the Wnt/beta-catenin signaling pathway were observed. Chondrogenic-differentiated ATDC5 cells were exposed to a 12% cycle tension load for 1, 2, 4, or 8 h. At each time point, immunofluorescence staining, western blot analysis, and qPCR were used to track the localization of beta-catenin and glycogen synthase kinase-3beta (GSK-3beta) expression. In addition, the mRNA expression of Wnt3a, disheveled homolog 1 (Dvl-1), GSK-3beta, and collagen type II were also detected. Activation of the Wnt/beta-catenin signaling pathway was investigated in cells treated with Dickkopf-related protein 1 (DKK-1). beta catenin and GSK-3beta protein expression increased initially and then decreased over the mechanical loading period, and the corresponding mRNA levels followed a similar trend. After application of the inhibitor DKK-1, Wnt/beta-catenin signaling was suppressed, and the mRNA expression of collagen II was also reduced. Thus, stimulation of chondrocytes with mechanical strain loading is associated with the translocation of active beta-catenin from the cytoplasm to the nucleus. PMID- 26821381 TI - Metabolite identification of the antimalarial piperaquine in vivo using liquid chromatography-high-resolution mass spectrometry in combination with multiple data-mining tools in tandem. AB - Artemisinin-based combination therapy is widely used for the treatment of uncomplicated Plasmodium falciparum malaria, and piperaquine (PQ) is one of important partner drugs. The pharmacokinetics of PQ is characterized by a low clearance and a large volume of distribution; however, metabolism of PQ has not been thoroughly investigated. In this work, the metabolite profiling of PQ in human and rat was studied using liquid chromatography tandem high-resolution LTQ Orbitrap mass spectrometry (HRMS). The biological samples were pretreated by solid-phase extraction. Data processes were carried out using multiple data mining techniques in tandem, i.e., isotope pattern filter followed by mass defect filter. A total of six metabolites (M1-M6) were identified for PQ in human (plasma and urine) and rat (plasma, urine and bile). Three reported metabolites were also found in this study, which included N-oxidation (M1, M2) and carboxylic products (M3). The subsequent N-oxidation of M3 resulted in a new metabolite M4 detected in urine and bile samples. A new metabolic pathway N-dealkylation was found for PQ in human and rat, leading to two new metabolites (M5 and M6). This study demonstrated that LC-HRMS(n) in combination with multiple data-mining techniques in tandem can be a valuable analytical strategy for rapid metabolite profiling of drugs. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26821384 TI - Exploring family-centered care for children living with HIV and AIDS in Nigeria. AB - AIM: To explored the role of family-centered care in supporting children living with HIV and AIDS in Nigeria. METHODS: A qualitative research design was adopted for this study with a grounded theory approach. Children aged between 11 and 14 years living with HIV and AIDS, their caregivers, and nurse practitioners working in the HIV clinic were engaged in separate focus group discussions in two hospitals in Nigeria. RESULTS: The findings showed that the value African families place on children plays a significant role in identifying their care needs and providing their basic necessities; hence, people around the sick child tend to make him feel better, as attested by nurse practitioners and caregiver participants. Nurse practitioner participants cited unified families as providing care support and love to the children and the support needed to alleviate their sicknesses. Children participants confirmed that family members/relatives were always at their disposal to provide supportive care in terms of administrating antiretroviral medication as well as other psychological care; although a few participants indicated that disruption in family structures in resource-poor settings, isolation and withdrawal, and deprivation of care due to poverty threatened the care rendered to the children. CONCLUSION: The study highlighted the value attached to children in the African context as helping family members to identify the care needs of children living with HIV and AIDS; thereby providing succor to alleviate their sicknesses and enhance their quality of life. PMID- 26821385 TI - Enhancement of functional MRI signal at high-susceptibility regions of brain using simultaneous multiecho multithin-slice summation imaging technique. AB - PURPOSE: To increase temporal-signal-to-noise ratio (tSNR) and blood oxygen level dependent (BOLD) sensitivity at high-susceptibility regions of the brain by means of a simultaneous multiecho multithin-slice summation imaging technique. MATERIALS AND METHODS: The simultaneous multislice (SMS) technique was implemented with multiecho (SMSME) and multiecho with thin-slice summation (SMSME thin) at 3T. Multiecho data were summated based on the local apparent T2* weighting factor. Ten healthy subjects were studied for the whole brain activation by breath-holding. The tSNR values and the number of activated pixels acquired with SMSME and SMSME-thin were compared with those acquired with the conventional gradient-echo EPI in multiple brain regions RESULTS: SMS methods accelerated imaging time by 5-fold as compared with the conventional method, resulting in the acquisition of three echoes and four thin-slices during the same TR of 2.5 seconds. At high-susceptibility regions, including the amygdala, inferior and middle temporal, and anterior frontal lobes, SMSME increased tSNR values by up to ~80% and BOLD activation by up to ~20% (paired t-test, P < 0.05). SMSME-thin further increased values as compared with SMSME (~45% for tSNR and ~20% for activation, P < 0.05). CONCLUSION: The SMSME-thin imaging technique enhanced the temporal-signal-to-noise ratio and functional activation at high susceptibility regions of the brain. J. Magn. Reson. Imaging 2016;44:478-485. PMID- 26821387 TI - The Editor's offering. PMID- 26821386 TI - Relevant Obstetric Factors for Cerebral Palsy: From the Nationwide Obstetric Compensation System in Japan. AB - OBJECTIVE: The aim of this study was to identify the relevant obstetric factors for cerebral palsy (CP) after 33 weeks' gestation in Japan. STUDY DESIGN: This retrospective case cohort study (1:100 cases and controls) used a Japanese national CP registry. Obstetric characteristics and clinical course were compared between CP cases in the Japan Obstetric Compensation System for Cerebral Palsy database and controls in the perinatal database of the Japan Society of Obstetrics and Gynecology born as live singleton infants between 2009 and 2011 with a birth weight >= 2,000 g and gestation >= 33 weeks. RESULTS: One hundred and seventy-five CP cases and 17,475 controls were assessed. Major relevant single factors for CP were placental abnormalities (31%), umbilical cord abnormalities (15%), maternal complications (10%), and neonatal complications (1%). A multivariate regression model demonstrated that obstetric variables associated with CP were acute delivery due to non-reassuring fetal status (relative risk [RR]: 37.182, 95% confidence interval [CI]: 20.028-69.032), uterine rupture (RR: 24.770, 95% CI: 6.006-102.160), placental abruption (RR: 20.891, 95% CI: 11.817-36.934), and preterm labor (RR: 3.153, 95% CI: 2.024 4.911), whereas protective factors were head presentation (RR: 0.199, 95% CI: 0.088-0.450) and elective cesarean section (RR: 0.236, 95% CI: 0.067-0.828). CONCLUSION: CP after 33 weeks' gestation in the recently reported cases in Japan was strongly associated with acute delivery due to non-reassuring fetal status, uterine rupture, and placental abruption. PMID- 26821388 TI - The Presidents' pages. PMID- 26821389 TI - The world as it is. British Sub-Aqua Club (BSAC) diving incidents report 2014. PMID- 26821391 TI - Bacterial contamination of suction catheter tips during aortic valve replacement surgery: a prospective observational cohort study. PMID- 26821392 TI - Honor your colleagues to support nurse education. PMID- 26821393 TI - [A case of a male in his 60's with prosthesis-related infections ]. PMID- 26821394 TI - [FACTORS ASSOCIATED WITH CHANGES IN THE NUMBER OF LATENT TUBERCULOSIS INFECTION NOTIFICATIONS IN JAPAN: NATIONWIDE SURVEY FINDINGS]. AB - PURPOSE: To investigate factors contributing to the drastic increase and subsequent decrease in latent tuberculosis infection (LTBI) notifications in 2011 (n = 10,046) and 2012 (n = 8,771), respectively, in Japan. METHODS: We conducted cross-sectional surveys in all 495 health centers in Japan in 2012 and 2013 using a semi-structured questionnaire that contained questions regarding the number of contacts listed for contact investigation, interferon-gamma release assay (IGRA) results, and incident of possible false positive IGRA results. RESULTS: Both the numbers and proportion of patients investigated using IGRA tended to increase from 2009 to 2012. However, the numbers and proportion of IGRA-positive patients, as well as that of those with borderline IGRA results, increased in 2011 and have decreased since 2012. In the 2012 survey, only 34 health centers (8%) reported questionable IGRA results. DISCUSSION: The removal of the age limit for LTBI treatment in 2010 may have contributed to the increase in the number of LTBI notifications in 2011, as the increase was particularly remarkable in the elderly age group. The increase in the proportion of positive and borderline IGRA results was likely partly due to expanded IGRA coverage that included more medical staff and the older population, which have a relatively high prevalence of tuberculosis infection, as well as a change from second-generation to third-generation QuantiFERON (QFT(r)) IGRA that offered increased sensitivity. The decrease in the number of outbreak incident cases and infectious patients may have contributed to the decrease in the number of LTBI notifications in 2012. CONCLUSION: Factors such as the increase in the number of patients undergoing IGRA, increase in the number of positive or borderline results due to QFT changes, and decrease in the number of tuberculosis outbreak incidents and infectious patients likely contributed to the increase and decrease in the number of LTBI notifications in 2011 and 2012, respectively. PMID- 26821395 TI - [CLINICAL EFFECTS OF TREATMENT FOR MYCOBACTERIUM TUBERCULOSIS INFECTION IN PATIENTS AT A SPECIALIZED HOSPITAL IN 2011]. AB - OBJECTIVE AND METHODS: We analyzed the clinical effects of treatment for Mycobacterium tuberculosis infection for 1 year in our specialized hospital in 2011. Two hundred and ninety-six (296) patients were admitted and received treatment. RESULTS: Two hundred and fifty-six patients (86.5%) were started on the standard treatment with 3 drugs (isoniazid [INH, rifampicin [RFP], and ethambutol [EB] or streptomycin [SM]) or 4 drugs (INH, RFP, EB or SM, and pyrazinamide [PZA]). One hundred and seventy-one patients (66.8%) continued receiving the standard treatment during the admission period. Of 160 cases who could continue 4 drugs, under 80 year-old patients were 127 cases (76.0%), but over 80 year-old patients were 33 cases (49.3%). The mean duration for negative conversion of sputum culture was 40.6 days. Liver dysfunction due to 4 drugs (INH, RFP, EB, and PZA) was noted in 8.5% of patients. Eighteen of the 296 patients had multi-drug resistant tuberculosis (MDR-TB). Each MDR-TB patient received individualized treatment. Moreover, 7 of the MDR-TB cases were treated surgically. DISCUSSION: Treatment of TB had taken long time, and some patients could not continue the treatment owing to the adverse effects of drugs. Hence, it is important to monitor adverse effects of drugs in each patient. PMID- 26821396 TI - [A CASE OF MILIARY TUBERCULOSIS ASSOCIATED WITH HEPATOSPLENIC ABSCESSES APPEARING DURING ANTI-TUBERCULOUS TREATMENT]. AB - A 27-year-old man with a 4-month history of treatment for miliary tuberculosis at another hospital was admitted to our hospital for continued treatment. Computed tomography showed new lesions in the S8 area of the liver and spleen, despite resolution of chest radiographic findings. Because these new lesions were still present after 8 months of treatment, we performed laparoscopic drainage of the liver abscess. Purulent material drained from the lesion revealed positive polymerase chain reaction results for Mycobacterium tuberculosis, and identification of granuloma with infiltrating lymphocytes and plasma cells confirmed the diagnosis of tubercular liver abscess. Pathological changes in the spleen over the clinical course were also regarded as representing tubercular abscess. Postoperative course was good, and tuberculosis treatment ended after 12 months. Tubercular liver abscess subsequently showed prominent reduction, and the tubercular splenic abscess disappeared on abdominal ultrasonography. Tubercular hepatosplenic abscesses appearing during tubercular treatment are rare. We report this valuable case in which laparoscopic drainage of a liver abscess proved useful for diagnosis and treatment. PMID- 26821397 TI - [TUBERCULOSIS SCREENING BY CHEST RADIOGRAPHY AMONG INTERNATIONAL STUDENTS AT JAPANESE LANGUAGE SCHOOLS IN OSAKA CITY]. AB - PURPOSE: With a broader aim of controlling pulmonary tuberculosis (TB) among foreigners, here, we have reported the findings of chest radiography screening for TB among international students at Japanese language schools in Osaka city. METHODS: Between April 2011 and December 2013, 4,529 international students from 19 Japanese language schools in Osaka city underwent chest radiography for TB screening. The chest radiographs were studied in reference to the student's sex, age, nationality, and date of entry to Japan as well as any health conditions present at the time of screening. We further analyzed the bacterial information and pulmonary TB classification based on chest radiography findings of students who were identified to be positive for TB. Information on the implementation of health education was also gathered. RESULTS: The results revealed that 52.5% of the students who underwent chest radiography came from China, 20.3 % from South Korea, and 16.3% from Vietnam. Of the students, 52.9% were male and 47.1% were female. The median age of students was 23 years (range: 14-70 years). The median number of days from the first date of entry to Japan up until the radiography screening was 63 days. Based on the chest radiography findings, 71 students (1.6%) were suspected to have TB; however, further detailed examination confirmed that 19 students (0.4%) had active TB. This percentage is significantly higher than the 0.1% TB identification rate among residents in Osaka city of the same time period (P<0.001), which was also determined by chest radiography. The median age of the 19 TB positive patients was 23 years. Among them, 14 (73.7%) were male. The median time from the date of entry to Japan to the date of the chest radiography screening was 137 days. For 16 of those students, the entry to Japan was within 1 year of the radiography. Of the 19 TB positive patients, 16 (84.2%) did not have respiratory symptoms, 15 (79.0%) had sputum smear negative results, and 17 (89.5%) had no cavity. Health education was conducted in 11 schools (for a total of 12 times) in the 3-year period. A total of 257 language school staff and students attended the health education seminars. DISCUSSION: The identification rate of TB positive students in Japanese language schools was higher than that of the general residents in Osaka city. In addition, most of these students came to Japan within 1 year. It is also important to note that the majority of TB positive students had sputum smear negative results. This study proves that medical examination after entry to Japan would be useful for early detection of TB positive patients. Furthermore, it would be beneficial to conduct chest radiography screenings among students at language schools on a continuous basis. It is also necessary to provide health education to the staff and students in Japanese language schools. Effective methods of disseminating health education, especially on the topic of TB, should be considered. PMID- 26821398 TI - PREDICTORS OF INFLAMMATORY LOCAL RECURRENCE AFTER BREAST-CONSERVING THERAPY FOR BREAST CANCER: MATCHED CASE-CONTROL STUDY. AB - BACKGROUND: Inflammatory local recurrence (ILR) after breast-conserving surgery for noninflammatory breast cancer (BC) is associated with dismal prognosis. Risk factors for ILR are not well defined. METHODS: Between 2001 and 2010, twelve patients at our hospital developed ILR after breast-conserving surgery, adjuvant chemotherapy, and radiotherapy for BC. We compared their clinico-pathological characteristics to those of 24 patients with noninflammatory local recurrence (non-ILR), 24 patients with distant metastases, and 48 disease-free controls, matched for age and observation period. RESULTS: The median time to ILR was 10 months. In univariate analysis, extent of lymph node involvement (p < 0.05), multifocality (p < 0.05), c-erbB2 overexpression (p < 0.05), and lymphovascular invasion (LVI) (p < 0.001) affected the risk of ILR. Conditional logistic regression analysis showed a significant association between ILR and combined LVI and high histopathological grade. The odds ratio (OR) for ILR versus non-ILR was 6.14 (95% confidence interval [CI] 1.48-25.38) and for ILR versus distant metastases it was 3.05 (95% CI 0.09-97.83) when both LVI and high histopathological grade were present. Patients with family history of BC were more likely to present with ILR than non-ILR (OR 5.47; 95% CI 1.55-19.31) or distant relapse (OR 5.62; 95% CI 0.26-119.95). CONCLUSIONS: Pre- and postmenopausal women with high-grade BC and LVI are at increased risk to develop ILR, especially in the presence of family history of BC. Identification of risk factors for this lethal form of recurrent BC may lead to more effective preventive treatment strategies in properly selected patients. PMID- 26821399 TI - PAROTID TUMORS: IS SURGERY ALWAYS THE ONLY WAY? AB - AIM OF THE STUDY: To analyze the characteristics and management of parotid tumors in a tertiary care center. STUDY DESIGN: Retrospective cohort study. METHODS: All cases of parotid tumors (or masses) in our department between Jan 1, 1999 and December 31st, 2012 were studied. Demographic data, clinical characteristics, histopathology and management were analyzed. We also evaluated the diagnostic value of fine needle aspiration cytology (FNAC) in our center. RESULTS: Of the 216 parotid tumors, 164 underwent parotidectomy and 52 were not managed surgically; 73.1% had a benign tumor (36.6% had Warthin's tumor) and 16.7% had a malignant one. In our center, FNAC was found to have a sensitivity for reporting malignancy of 71.4% and a specificity to rule in malignancy of 100%. CONCLUSION: In our series, Warthin's tumor was the most frequent mass probably related to the high tobacco use. The prevalence of malignant tumors was relatively high in our series. Primary malignant tumors and pleomorphic adenomas should always be treated surgically, however, lymphomas, metastatic and benign inflammatory masses and cases of Warthin's tumors could be managed nonsurgically. PMID- 26821400 TI - EFFECTS OF PREOPERATIVE ENOXAPARIN ON BLEEDING AFTER CORONARY ARTERY BYPASS SURGERY. AB - BACKGROUND: Low molecular weight heparins are replacing unfractionated heparin in practice prior to cardiac surgery. This study examines postoperative (post-op) bleeding indicators in patients who received enoxaparin and underwent elective isolated first time coronary artery bypass graft. METHODS: A total of 125 consecutive patients who underwent this procedure between 2009 and 2011 at one tertiary center were reviewed and divided into three groups: Group A (n = 50) received the last dose of enoxaparin between 12 and 24 hours before surgery, Group B (n = 25) received the last dose before 24 hours and Group C (n = 50) did not receive enoxaparin. Perioperative bleeding indicators and transfusion rates were compared. RESULTS: Preoperative patients' characteristics were comparable between the three groups. There were no perioperative deaths, return to the operating room for any reason, nor major bleeding. Post-op bleeding indicators were similar in the three groups. The average chest tube drainage at 24 hours post-op was 880 mL, 695 mL and 830 mL in Group A, B and C respectively (p = 0.71). Transfusion rates of red blood cells were not statistically different (Group A 56%, B 64% & C 62%; p = 0.747). In multivariate analysis, female gender, older age, and preoperative clopidogrel intake (stopped 5 days prior to surgery) were associated with higher transfusion rates. CONCLUSION: In elective first time coronary artery bypass graft patients who had no aspirin or clopidogrel intake 5 days prior to surgery, the use of enoxaparin up to 12 hours prior to skin incision does not increase the risk of post-op bleeding. PMID- 26821401 TI - [Geriatric profile according to the Identification of Seniors At Risk (ISAR) tool in the emergency department in a teaching hospital]. AB - BACKGROUND: With the anticipated increase in the number of elderly people in Lebanon, it is important to develop services tailored to their specific needs. The Identification of Seniors At Risk (ISAR) tool identifies, in emergency setting, frail elderly people at risk of adverse outcomes, who are more likely to benefit from a geriatric approach. OBJECTIVES: i) Assess the geriatric profile according to ISAR score ii) correlate the score to outcomes two months after Emergency Department (ED) visit. METHODS: A two-month prospective study: at the ED of Hotel-Dieu de France Hospital, we interviewed 273 people aged 70 years and older (or their caregiver) using the ISAR tool. Telephone follow-up was done two months later. RESULTS: The prevalence of subjects with ISAR score >= 2 and thus likely to benefit from the establishment of a geriatric service is 70.7% (95% CI: 64.9-76.0). Elderly patients admitted to ED with ISAR score >= 2 are more likely to be hospitalized (51.6%) than subjects of the same age and sex with ISAR score < 2 (36.9%) (p = 0.034). After two months of follow-up, the risk of hospital readmission and the risk of death was significantly associated with the ISAR score (p = 0.0005) CONCLUSION: The percentage of elderly people likely to benefit from specialized geriatric care network upon admission to the ED of a university hospital is significantly high [70.7% (95% Cl: 64.9-76 .0)]. PMID- 26821402 TI - FALSE AND TRUE ACUTE RHEUMATIC FEVER: A Lebanese Experience. AB - OBJECTIVES: The main aim of this study is to evaluate the significance of several clinical and laboratory findings presented by a large number of pediatric patients who were suspected to have acute rheumatic fever (ARF) by physicians who ordered echocardiogram for confirmation and for avoiding overuse of unnecessary antibiotics. These suspecting reasons include elevated ASO titers and recurrent tonsillitis. Another aim is to stress the role of Doppler echocardiogram in confirming the diagnosis of ARF by detecting rheumatic heart disease (RHD) in suspected cases. MATERIALS AND METHODS: 401 patients were registered in the National Registry of the Pediatric and Congenital Heart Disease (RNCPC) from April 1, 2002 until the end of March 2013 as suspected cases of ARF. The clinical reasons that brought suspicion are discussed and evaluated in accordance to modified Jones criteria. The patients are distributed into two groups: 1) confirmed ARF and 2) different diagnosis. All patients underwent echocardiogram. Patients came from different geographic areas and were referred by a variety of physicians. RESULTS: 48 patients out of 401 suspected cases turned to have confirmed ARF (12%). In this group, the predominant suspecting reasons are reported as heart murmur in 29/48 (60.4%), arthritis in 28/48 (58.3%), arthralgia with reduced physical activity in 15/48 (31%) and chorea in 5/48 (10%). In the different diagnosis group with a high ASO titer 174/353 (49.3%), isolated arthralgia 91/353 (25.8%) and combined elevated ASO with arthralgia in 44/353 (12.5%) were the predominant suspecting reasons. Doppler echocardiography could detect 38/48 cases of active carditis and subclinical carditis (SCC). CONCLUSION: Heart murmur, arthritis, arthralgia with reduced physical activity and chorea are the main clinical reasons that lead to suspicion in the ARF group. High ASO titers, arthralgia, and combination of high ASO titers with arthralgia are the main presenting symptoms in the group with a different diagnosis. We concluded that elevated ASO titer and normal ESR with arthralgia not reducing physical activity can exclude ARF. Doppler echocardiography is found to be a gold standard key to confirm acute rheumatic heart disease and ARF. PMID- 26821403 TI - NASALANCE SCORES IN LEBANESE ENGLISH-SPEAKING ADULTS USING NASOMETRIC ANALYSIS. AB - OBJECTIVE: To obtain normative data for nasalance scores in Middle Eastern English-speaking adult population. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 102 subjects were recruited in the study, 26 were excluded, thus, 77 Middle Eastern English-speaking adults (mean age = 23.77 +/- 4.295; 39 males, 38 females) with normal speech and no hearing problems participated in the study. INTERVENTIONS: Using Nasometer II 6450, nasalance scores were obtained for each participant's readings of 3 passages: Zoo and Rainbow passages and nasal sentences. MAIN OUTCOME MEASURES: Mean nasalance score, standard deviation and range. RESULTS: Mean nasalance scores for Zoo passage, Rainbow passage and nasal sentences were 25.21 +/- 11.07, 34.04 +/- 9.30 and 41.29 +/- 9.87 respectively. Mean scores didn't differ significantly between males and females, though scores for the Zoo passage were slightly higher among males (26.51 +/- 11.66) than females (23.87 +/- 10.42). In within-session reliability testing, 86% of retests for all three passages fell within 5 nasalance points of the previous test. In across-session reliability testing, 93% of retests for all 3 passages were within 5 points of initial test. CONCLUSIONS AND RELEVANCE: This study provides normative data for nasalance scores among Middle-Eastern adults, which can help make nasometer and determination of nasalance more clinically useful in this population. PMID- 26821404 TI - FORMANT CHARACTERISTICS OF ENGLISH-SPEAKING LEBANESE MEN. AB - OBJECTIVE: To report the formant characteristics of English-speaking Lebanese men during steady prolongation of vowels /a/ and /i/. DESIGN: Cross-sectional study involving volunteer participants. PARTICIPANTS: Fifty healthy English-speaking males with a mean age of 32 +/- 4.027 years and a range of 42 years (18-60). MATERIALS AND METHODS: A total of 50 healthy males between the age of 18 and 60 were recruited for the study. Each subject was asked to phonate a sustained /a/ and /i/ sound at a comfortable pitch and intensity level. Measures were made in real-time and formant frequencies across F1, F2, F3 and F4 were determined using the Real-time Spectrogram VP 3950 (Kay Elemetrics, New Jersey). MAIN OUTCOME MEASURES: The formant frequencies across F1, F2, F3 and F4 were recorded. RESULTS: For the vowel /a/, the mean values of F1, F2, F3 and F4 were 622.86 +/- 61.293 Hz, 1264 +/- 78.602 Hz, 2610.90 +/- 206.359 Hz and 3483.56 +/- 206.833 Hz, respectively. For the vowel /i/, the corresponding values were 378.88 +/- 51.825 Hz, 2210.34 +/- 124.077 Hz, 2847 +/- 168.770 Hz and 3576.82 +/- 242.760 Hz, respectively. CONCLUSION: Formant characteristics vary among cultures and ethnic groups. PMID- 26821405 TI - TOWARDS DEVELOPING A SUSTAINABLE FACULTY DEVELOPMENT PROGRAM: An Initiative of an American Medical School in Lebanon. AB - INTRODUCTION AND OBJECTIVES: The American University of Beirut Faculty of Medicine (AUB-FM) strategy is to develop faculty members (fm) skills by sponsoring local and international scientific activities has been in place for over three decades, and remains dependent on individuals' efforts. In 2011-2012, Faculty Development Program (FDP) was introduced to develop faculty leadership, business skills in medicine, fulfill personal and professional goals, followed by a five-year plan to cover five themes: Management/Leadership, Marketing, Finance, Strategic Planning and Communications with the purpose of integrating these themes in medical practice. METHODS: A survey was sent to all departments at AUB FM in 2011 to assess needs and determine themes. Nine workshops were conducted, followed by post-workshop evaluation. RESULTS: 117 fm responded to needs assessment surveys. Respondents had on average 15 years in clinical practice, 50% with extensive to moderate administrative experience; 71% assumed administrative responsibilities at least once, 56% in leadership positions. Faculty attendance dropped midway from 69 to 19, although workshops were rated very good to excellent. DISCUSSION: Although faculty were interested in FDP, the drop in attendance might be attributed to: challenges to achieve personal and professional goals while struggling to fulfill their roles, satisfy promotion requirements and generate their income. RECOMMENDATIONS: FDP has to be aligned with FM strategic goals and faculty objectives, be complimentary to a faculty mentoring program, provide rewards, and be supported by a faculty progression tool. PMID- 26821406 TI - MANAGEMENT OF METASTATIC COLORECTAL CANCER: Current Treatments and New Therapies. AB - Colorectal cancer represents 8% of metastatic cancers. For decades, the gold standard therapy has been infusional chemotherapy with 5-Fluorouracil (5-FU) associated to folinic acid. The discovery of irinotecan, oxaliplatin and oral forms of 5-FU in the nineties is considered a milestone in the treatment of this disease. Since 2004, targeted therapy with monoclonal antibodies including anti EGFR and angiogenesis inhibitors showed superiority in terms of mortality compared to conventional therapy. Metastatic colorectal cancer, however, remains an incurable disease. We present the current treatments of metastatic colorectal cancer, the clinical development of these emerging treatments, and their position in the Lebanese health care system. PMID- 26821407 TI - CEREBRAL ANEURISMAL RUPTURE WITH SUBARACHNOID HEMORRHAGE DURING PREGNANCY: A CASE REPORT. AB - BACKGROUND: Intracranial hemorrhage due to arteriovenous malformation or intracranial aneurysm is a rare but severe complication of pregnancy with maternal and fetal mortality of 20% and 33% respectively. Whether to deliver the patient first, or to treat the aneurysm first is still controversial, but an emergency cesarean section followed by aneurismal treatment appears to be a widely accepted strategy in pregnant women with cerebral aneurysmal complications. CASE: A 38-year-old patient, G3P2A0, presented at 36 gestational weeks with a diffuse bilateral subarachnoid hemorrhage with fourth ventricle bleeding and hydrocephalus. She had a cerebral aneurysm of the left posterior communicating artery on arteriography. A cesarean section was performed on the first day of admission, and an external ventricular derivation with clipping of the aneurysm on the left posterior communicating artery were done immediately after the cesarean section. Mother and newborn were discharged from hospital in a good health status except Broca's aphasia in the mother. CONCLUSION: In the absence of categorical recommendations, we stress the role of combined care by both neurosurgeons and obstetricians, on a case to case basis according to gestational age, mother neurological status and experience of caregivers. PMID- 26821409 TI - [Chronic hepatitis C in Russia: current challenges and prospects]. AB - This paper evaluates the impact of different medical care strategies for chronic hepatitis C patients in relation to its prevalence, frequency of adverse outcomes and mortality rate. PMID- 26821410 TI - [Brucellosis in the Stavropol Territory: Results of 15-year follow-up of epidemiological and clinical features]. AB - AIM: To analyze the epidemiological situation of brucellosis in the Stavropol Territory and to determine the specific features of its acute form. MATERIALS AND METHODS: The epidemiological situation of brucellosis in the Stavropol Region was retrospectively analyzed using the 2000-2014 official statistics of the Russian Federation and Stavropol Territory for brucellosis cases, individual documents of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare Directorate in the Stavropol Territory and Russian Federation, and medical records of the Brucellosis Department, Stavropol Hospital Two. RESULTS: Brucellosis is a social problem in a group of focal zoonotic infections in the Russian Federation. In the North Caucasian Federal District, the largest number of new human brucellosis cases was notified in the Republic of Dagestan (59.3%) and Stavropol Territory (27.4%). The incidence of brucellosis in the Stavropol Territory was 5-10-fold higher than that in the Russian Federation as a whole. The true prevalence of brucellosis was 25% greater than the statistical data in terms of its clinical forms that were not included in official registration. Infection occurred in humans by contact with large and small cattle in 49.7% of cases. The disease mainly affected men (78.3%) and able-bodied people (67.7%); 78.5% of the patients seeking medical advice and as high as 79.9% of those being covered by serological examination of groups at risk for brucellosis were detected. There was a declining trend for the number of occupational brucellosis cases. At the same time, brucellosis accounted for 75% of the territory's total number of occupational diseases. In the past decade, brucellosis has exhibited a relatively benign course (91.3% for its moderate form), by predominantly involving the osteoarticular system (63%). Non-compliance with outpatient antibacterial therapy is one of the factors for brucellosis chronization. 28.2% of the patients who had undergone a complete therapy cycle developed chronic brucellosis less frequently (p < 0.005) than those who had stopped treatment for different reasons. CONCLUSION: Registration of brucellosis among humans is a result of the unfavorable epizootic situation of animal brucellosis. The highest incidence of brucellosis is observed in the northeastern areas of the Stavropol Territory, which border the Republic of Dagestan. The true prevalence of brucellosis greatly exceeds the official statistical data. Active detection of infection and timely diagnosis will be able to determine the real epidemic situation of brucellosis. Continuity of management and follow-up will provide a reduction in medical and social losses associated with this infection. PMID- 26821411 TI - [Relapsing (recurrent) disease caused by Borrelia miyamotoi]. AB - AIM: To clarify the clinical, laboratory, and epidemiological characteristics of relapsing Ixodes tick-borne borreliosis (ITB) caused by Borrelia miyamotoi. SUBJECTS AND METHODS: Retrospective clinical observation was made in 79 inpatients of the Republican Infectious Diseases Hospital (Udmurt Republic), who had been diagnosed with B. miyamotoi-caused disease verified by real-time polymerase chain reaction. The latter and enzyme immunoassay ruled out possible vector-borne coinfections (ITB caused by B. burgdorferi sensu lato; tick-borne encephalitis; anaplasmosis; and ehrlichiosis). RESULTS: The recurrent course of the disease was observed in 8 (10%) of the 79 patients. The relapsing fever curve was noted in 6 of the 8 patients; 4 patients had 2 episodes of fever and 2 patients had 3 episodes; the wave-like continuous type of fever cannot enable one to estimate the specific number of episodes in 2 more cases. Relapses occurred in all the 8 patients before antibiotic treatment. Febrile syndrome (weakness, headache, chill, fever, sweating, dizziness, nausea, vomiting, myalgia, and arthralgia) was leading in patients with relapses. These patients were less frequently observed to have signs of organ dysfunctions than those with one episode of fever. The values of clinical and biochemical blood tests and urinalyses were normal and near-normal in the majority of patients on hospital admission. CONCLUSION: Relapsing B. miyamotoi infection cases detected in the directed study proved to be unrecognized by practical health authorities during the first and sometimes second episodes of fever. This indicates that the prevalence of this disease is essentially underestimated and there is a need to increase physicians' alertness and awareness and to introduce adequate diagnostic methods. PMID- 26821412 TI - [The blood coagulation system and microcirculatory disorders in ixodid tick-borne borreliosis caused by Borrelia miyamotoi]. AB - AIM: To study blood coagulation and microcirculatory disorders as a possible cause of transient dysfunctions of organs (the kidney, liver, heart, lung, etc.) in patients with ixodid tick-borne borreliosis caused by Borrelia miyamotoi (Bmt). SUBJECTS AND METHODS; Twenty-four patients with Lyme disease (LD) and 28 Bmt patients treated at Izhevsk City Hospital (Udmurtia) were examined in the study. Platelet counts and the presence of D-dimers were determined; activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen and antithrombin III levels, and Factor XIIa-dependent fibrin clot lysis time were measured. Slit lamp microscopy of the conjunctiva was. also carried out. Results. Platelet counts'were less than 150,000 per pL of blood in 43% of the Bmt patients. All the Bmt patients had at least one abnormal coagulation parameter of the eight ones that were tested; 64% of them had marked coagulation disorders with three or more abnormal laboratory findings. In contrast, all the eight parameters were normal in 71% of the LD patients. The other seven LD patients had only one or two abnormal coagulation parameters (p < 0.001 in comparison with Bmt patients). Microscopic examination of eye capillary blood flow revealed pathological findings that included aggregates of erythrocytes and obstructed and/or sinuous capillaries in 22 (79%) of the Bmt patients, but none of the LD patients. A total of 14 Bmt patients had both coagulation and microcirculatory abnormalities. Eleven of them also had transient signs of organ dysfunction. CONCLUSION: As far as Borrelia secrete no known toxins, we hypothesized that uncovered disorders of blood coagulation and microcirculation in Bmt patients may contribute to organ dysfunction. PMID- 26821413 TI - [HIV infection risk perception and stigmatizing attitude: Results of surveys of dwellers from the Central Administrative District of Moscow]. AB - AIM: To study human immunodeficiency virus (HIV) infection risk perception and stigmatizing attitudes in the dwellers of the Central Administrative District of Moscow. SUBJECTS AND METHODS: An anonymous survey was conducted using specially developed questionnaires. A total of 893 people were interviewed. Each of the given indicators was used to ask 98 to 254 respondents. Among the survey participants, there were 92 healthcare workers, including 66 physicians and 26 representatives of middle-level and junior medical staff. According to their replies, the respondents were divided into 2 groups: 1) healthcare workers; 2) representatives of the so-called general population. RESULTS: 91.3% of the healthcare workers gave a negative reply to the question: "Should contacts (intercourse) with people living with HIV (AIDS) be avoided to escape infection?". In Group 2, 58.8 and 23.5% of the respondents answered negatively and positively, respectively; and 17.6% had difficulty answering the question. In the general population group, 44.10% of the respondents answered negatively and 32.2% had difficulty answering the question: "Would you agree to live in the same room with anybody whom you know or suspect to be HIV positive?"; 23.8% agreed to do this. Among the healthcare workers, there were 46.7% of the respondents who answered positively. When the question: "Would you agree to send your child (grandson) to the kindergarten if you would learn that a HIV-infected child goes there?" was asked, 48.6 and 18.7% of the respondents in the general population group answered negatively and positively, respectively; 32.7% had difficulty answering. In the group of healthcare workers, 66.7% answered positively. Among both the healthcare workers and the representatives of the general population, more than 60% of the respondents agreed with the statement that "HIV-infected people lead a loose life". CONCLUSION: The specific features of perceiving a HIV infection risk and showing stigmatizing attitudes towards HIV-infected patients make the forming less dangerous behaviors difficult and restrict an access to care and support in infected patients. The training of healthcare workers in issues related to HIV infection should involve the identification of stigmatizing attitudes and the application of destigmatization strategies. PMID- 26821415 TI - [Follow-up study of HIV-infected patients with prior cerebral toxoplasmosis]. AB - AIM: To assess follow-up study results in human immunodeficiency virus (HIV) infected patients with prior cerebral toxoplasmosis (CT). SUBJECT AND METHODS: Follow-up study results were assessed in HIV-infected patients with prior CT. RESULTS: The fate of only 97 out of 137 (66% of the hospitalized) patients discharged from hospital is known, as 40 convalescents have been lost to follow up. Thereafter, relapses developed in 19 patients, of whom 6 died. Eleven more patients with HIV infection died due to its progression and development of other secondary lesions. Five more patients died from narcotic overdose, staphylococcal sepsis, and acute pancreatic necrosis. The main peak of fatal outcomes was within the first 2 years after discharge. 3.5-year survival rates after TC were 75%. The causes of recurrent and progressive HIV infection were non-compliance with secondary prevention of CT and low adherence to an antiretroviral therapy regimen, the blame of which fell not only on the patients, but also their attending physicians and specialists who had advised how to enhance treatment motivation. CONCLUSION: Further follow-up of convalescent CT patients calls for closer attention to the possible development of recurrences within the first three years after discharge in particular, regardless of CD4 cell counts. PMID- 26821414 TI - [Impact of etiotropic therapy on the immune status of patients with HIV infection and tuberculosis]. AB - AIM: To evaluate the impact of etiotropic therapy on the immunological efficiency of treatment in patients with HIV infection in relation to the presence of active tuberculosis (TB) and the baseline count of CD4+ lymphocytes. SUBJECTS AND METHODS: A total of 239 HIV-infected patients were examined and divided into 3 groups: 1) 103 HIV-infected patients with TB who received both anti-TB therapy (ATBT) and antiretroviral therapy (ART); 2) 46 HIV-infected patients with TB who did not receive ART during TB treatment; 3) 90 HIV-infected patients without TB who used ART for the first time. CD4+ lymphocyte counts were measured by flow cytofluorometry in all the patients before and 4 and 12 weeks after treatment. RESULTS: Analysis of an increment in CD4+ lymphocyte counts in the HIV-infected patients with tuberculosis showed that those who had very low baseline CD4+ lymphocyte counts (median, 78 cells/MUl) were noted to have significant positive changes (median, +146 cells/MUl) at 12 weeks of ART. Even without ART, effective ATBT in the patients with a well preserved immune system (> 350 CD4+ cells/MUl) in turn resulted in a substantial increase in CD4+ lymphocyte counts (median, +187 cells/MUl following 12-week ATBT). At the same time, 10.9% of the patients showed a decrease in the baseline CD4+ lymphocyte counts during progression or delay in the tuberculosis process, which required that ART should be promptly performed. CONCLUSION: The investigation of the time course of changes in the increment of CD4+ lymphocyte counts revealed a swifter response to ART as their rapid increment in patients with coinfection (HIV infection concurrent with TB) than that in those with HIV monoinfection. When the baseline CD4+ lymphocyte counts are over 350 cells/MUl, the start of ART should be delayed until TB treatment is completed. PMID- 26821416 TI - [Assessment of factors influencing the outcome of new-onset infiltrative pulmonary tuberculosis]. AB - AIM: To identify predictors for the poor outcome of infiltrative pulmonary tuberculosis (IPTB). SUBJECTS AND METHODS: The social, epidemiological, and medical risk factors and clinical features of IPTB were assessed in 130 first detected patients. The findings were classified using a cluster analysis and then a variance analysis, followed by the ranking of its results. RESULTS: The primarily diagnosed disseminated destructive process with respiratory and cardiopulmonary failure, excretion of both resistant and multi-resistant pathogenic bacteria had a strong impact on the poor outcome of tuberculosis (TB) in the first detected patients. Its outcome was also influenced by a set of social factors, such as poor material living conditions, stay in corrective labor facilities, and a lack of education. The unfavorable outcome of TB was significantly due to organizational factors, such as bad habits; refusal to undergo fluorography during a few years; and a medical factor as comorbidities. CONCLUSION: Based on the identified factors, the authors formulated recommendations for working with the first detected IPTB patients at risk for a poor disease outcome. PMID- 26821417 TI - [Combination drugs in the therapy of acute respiratory viral infections: Evaluation of clinical and economic effectiveness]. AB - AIM: To make a comparative clinical and economic evaluation of the use of the combination drug Influnet in the treatment of acute respiratory viral infections (ARVI). SUBJECTS AND METHODS: A total of 103 medical records of outpatients with uncomplicated mild and moderate ARVI were studied. There were three groups: 1) 35 patients who received therapy with Influnet; 2) 31 patients who took Rinza; 3) 34 patients who were on treatment without the combination drug. RESULTS: Analysis of comparative clinical effectiveness of the drugs revealed that the use of Influnet was accompanied by the rapider alleviation of fever and other ARVI symptoms and by its shorter treatment duration (4.5 +/- 0.5 days) versus that of Rinza (5.5 +/ 1.4 days) and monocomponent drugs (5.6 +/- 1.2 days). Economic analysis showed that in terms of indirect costs associated with shorter temporary disability in patients with ARVI, Influnet therapy was more economically sound for them. CONCLUSION: The results demonstrate the higher clinical and economic feasibility of Influnet therapy for ARVI versus its alternative therapy. Combination drugs cause fewer adverse reactions than a combination of monocomponent drugs used to treat ARVI and are more cost- effective for the patient. PMID- 26821418 TI - [Inflammatory diseases of scrotal organs in patients with brucellosis: Improvement of therapy]. AB - AIM: To evaluate the efficacy of cycloferon used in the combination treatment of scrotal inflammatory diseases (SID) in patients with brucellosis. SUBJECTS AND METHODS: A total of 150 male patients with chronic brucellosis (CB) were examined. Inquiry, questioning, physical and ultrasound examinations, and spermiogram analysis were used to detect of diseases of the reproductive system. Twenty-two CB patients with SID were examined over time (before and after cycle therapy). In Group 1, combination therapy included 2 cycles of five intramuscular injections of cycloferon 0.25 g in each at a 10-day interval. In Group 2, a package of therapeutic measures meets the generally accepted standards. and Incorporation of cycloferon into the combination therapy of SID patients with CB positively affected the time course of clinical changes and spermatogenesis, declines the number of SID exacerbations, improved quality of life, and failed to cause side effects. CONCLUSION: The findings allow us to recommend cycloferon as the drug of choice in treating CB patients with SID. PMID- 26821419 TI - [Survival in pulmonary arterial hypertension, associated with connective tissue diseases, treated by sildenafil: results of the prospective study]. AB - AIM: To investigate the effect of sildenafil on the survival of patients with pulmonary arterial hypertension (PAH) associated with connective tissue diseases (CTD), who have been followed up at the Rheumatology Expert Center. SUBJECTS AND METHODS: A total of 16 patients (all women) with PAH associated with CTD, who had been admitted to the V. A. Nasonova Research Institute of Rheumatology in 2013 2015, were examined. PAH corresponded to Functional Class II in the majority of the patients. After the diagnosis was verified by catheterization of the right heart and pulmonary artery, all the patients received original sildenafil (a phosphodiesterase type 5 inhibitor, a potent vasodilator, the efficiency of which was proven in patients with PAH) at a dose of 20 mg thrice daily. Survival rates and time to clinical deterioration were estimated during a prospective follow up). RESULTS: Three-year survival rates were 94% in the study group and 25% in the group of historical control (p < 0.05). The time to clinical deterioration was associated with the duration of the follow-up and hemodynamic parameters (right atrial pressure and changes in vascular resistance within 4 months after therapy initiation). CONCLUSION: The administration of sildenafil substantially improves survival in patients with PAH associated with CTD as compared with the historical control. The identification of poor prognostic factors in this cohort of patients and early diagnosis will favor the personification of therapy for the fatal manifestation of CTD. PMID- 26821420 TI - [Genes of killer cell immunoglobulin-like receptors and their HLA ligands after allogeneic hematopoietic stem cell transplantation in myeloid leukemia patients]. AB - AIM: To study the impact of the genes of donor killer cell immunoglobulin-like receptors (KIR) and HLA-KIR ligands on overall (OS) and event-free survival (EFS) rates in patients with myeloid leukemia after transplantation with allogeneic hematopoietic stem cells (allo-HSCT) from HLA-identical related and HLA compatible unrelated donors. SUBJECTS AND METHODS: The investigation enrolled 29 patients who had undergone allo-HSCT from KIR-genotyped donors at the Department of Bone Marrow Transplantation, Hematology Research Center (see symbol) in 2010 2013. OS and EFS rates after allo-HSCT were calculated using the Kaplan-Meier method. RESULTS: The main predictor of recurrence and survival in patients after allo-HSCT was a recurrence-risk group the patient belonged to before transplantation. The standard-risk group patients whose donors had telomeric gene content motifs of KIR-B haplotypes had higher EFS rates than those whose donors lacked these genes. The standard-risk patients homozygous for HLA-1 alleles (i.e. without HLA-C2 ligand) tended to have higher EFS rates, so did the patients without HLA-Bw4 ligand. CONCLUSION: The donors having telomeric gene-content motifs of KIR-B haplotypes are more preferred for allo-HSCT for patients with myeloid leukemia as the presence of donor telomeric KIR-B genes increases EFS rates in standard-risk patients. PMID- 26821421 TI - [Nodular lymphocyte-predominant Hodgkin's lymphoma: Principles of diagnosis and treatment]. AB - AIM: To describe the clinical and morphological features of the rare Hodgkin's lymphoma (HL) subtype--nodular lymphocyte-predominant HL (NLPHL). SUBJECTS AND METHODS: Forty-two patients were diagnosed with NLPHL in 2010 to 2014. The male to female ratio was 2.2:1; the median age was 37 years (range 17-68 years). NLPHL was diagnosed on the basis of the histological and immunohistochemical examinations of tumor biopsy specimens; disease stages were determined by standard HL studies. RESULTS: Before NLPHL was detected, 23 (55%) patients were diagnosed as having HL in 13 cases, follicular lymphoma in 2, lymphofollicular hyperplasia in 3, angioimmunoblastic lymphoma in 1, diffuse large B-cell lymphoma in 3, and B-cell lymphoma (non-HL) in 1. Long-term (3-21-year; median 8 years) persistent lymphadenopathy was observed in 16 (38%) patients. Seventeen (40.5%) patients had early (I-II) stages of the disease and 25 (59.5%) had advanced stages. B symptoms were noted in 24% of cases. There was involvement of extranodal sites (salivary gland, tonsil) in 2 patients, spleen in 14 (33%), bone marrow in 8, and bulky disease in 2. Cycles of ABVD +/- rituximab +/- radiotherapy (RT) were used in early-stage NLPHL; those of R-BEACOPP-14 +/- RT were performed in the advanced stages of the disease or its transformation to diffuse large B-cell lymphoma with excessive T cells. CONCLUSION: When patients have a history of long-term asymptomatic lymphadenopathy, it is necessary to rule out NLPHL, for which purpose an immunohistochemical examination of a biopsy specimen and its reexamination in a laboratory having experience in diagnosing NLPHL must necessarily be done. Lower RT doses and rituximab incorporated into the cycle of treatment are indicated to reduce its toxicity and to preserve therapeutic efficiency. PMID- 26821422 TI - [Description of a case of severe Q fever]. AB - The paper considers a rare clinical case of severe Q fever in a young man with no compromised premorbid background. It describes and analyzes clinical manifestations and laboratory findings with consideration for the current data available in the literature. The issues of the differential diagnosis, laboratory diagnosis, and treatment of Q fever are discussed. PMID- 26821423 TI - [A case of adenovirus infection complicated by gram-negative polymicrobial sepsis: A clinical and morphological observation]. AB - Among respiratory infections, adenovirus infection (ADVI), in the presence of which there may be severe pneumonia that frequently results in a fatal outcome, occupies particular attention. ADVI in patients without immunodeficiency is usually mild and shows a limited extent of injury. At the same time the disease in immunocompromised individuals may be severe, presenting with viremia, evolving sepsis, and high death rates. The paper gives a characteristic example of severe ADVI and its fatal outcome. PMID- 26821424 TI - [Secondary diseases and Burkitt's lymphoma in HIV-infected patients]. AB - The authors give the clinical data of 110 human immunodeficiency virus (HIV) infected patients who stayed in a correctional facility during 2014. Of the examinees, there were almost 50% of the patients with advanced stages (IVA-IVB) with different secondary/opportunistic diseases, among which was Burkitt's lymphoma, a rather rare malignant disease that developed in obvious immunodeficiency in the absence of antiretroviral therapy. PMID- 26821425 TI - [Successful treatment for cryptococcal meningoencephalitis complicated by cerebral salt-wasting syndrome in a patient with chronic lymphocytic leukemia: A clinical case]. AB - Cryptococcus neoformans is a common agent of fungal meningoencephalitis in immunocompromised patients. Cerebral salt-wasting syndrome is one of the rare causes of severe hyponatremia in patients with CNS diseases. The paper describes the first clinical case of a patient, whose onset of chronic lymphocytic leukemia was complicated by cryptococcal meningoencephalitis presenting with mental disorders and severe electrolytic imbalance. Antifungal treatment with amphotericin B and fluconazole could alleviate an infectious process and metabolic disturbances. PMID- 26821427 TI - [Spread of nosocomial infection in obstetric hospitals]. AB - The paper highlights the topical problems of nosocomial infection in the practice of obstetrics and perinatology. It systematizes procedures for controlling the occurrence of nosocomial infection and preventing its spread, such as identification of risk groups and risk factors and prerequisites for complications of epidemiological surveillance, as well as specific diagnosis in pregnant women. Group B streptococcus, one of the major pathogens of nosocomial infection, is described. PMID- 26821426 TI - [Microbial dormancy and prevention of healthcare-associated infections]. AB - Healthcare-associated infections (HCAI) remain one of the most challenges of modern health care and assume increasing social and medical significance. The specific features of HCAI are frequent recurrences and inefficiency of antibiotic therapy, a reason for which is antibiotic resistance in microorganisms. The review discusses antibiotic resistance, a form of antibiotic tolerance (AT), and its role in the development of HCAI. It also describes essential differences between AT and antibiotic tolerance at the cellular and molecular genetic levels. Relationships between AT and dormancy of microorganisms, pathogens of HCAI, are discussed. The paper gives the data available in the literature on how AT occurs in HCAI pathogens and discusses the diagnosis of this condition. It also analyzes the literature data on pharmacological attempts to overcome AT and discusses novel approaches to antibiotic therapy for HCAI. PMID- 26821428 TI - [Topical problems of antiviral therapy for chronic hepatitis C]. AB - Antiviral therapy using interferon-free regimens for chronic hepatitis C (CHC) is being more frequently practiced by hepatologists due to the high efficiency of a short treatment cycle and the lowest rate of adverse events. The review discusses the most topical problems that will present themselves in practicing hematologists when treating patients with CHC under the present-day conditions. The use of direct-acting antiviral drugs requires knowledge and skills for physicians to orient themselves in the list of these drugs to create their based regimens, the efficiency and safety of which are proven in the context of evidence-based medicine. The review gives data on the efficiency and safety of 3D therapy for CHC according to the baseline characteristics of patients. PMID- 26821429 TI - [Approaches to antiretroviral therapy in HIV-infected patients with low CD4 lymphocyte counts]. AB - There are increasing numbers of patients with late-stage HIV infection in the Russian Federation. To choose optimal antiretroviral therapy regimens for patients with severe immunosuppression is a relevant problem. According the data obtained in the ECHO and THRIVE, ARTEMIS, CASTLE, SPRING-2 and other trials, the efficacy and/or safety of efavirenz are higher than those of rilpivirine, comparable with those of raltegravir and dolutegravir; darunavir and atazanavir are more effective than lopinavir, but dolutegravir is more effective than raltegravir (in numerical terms) in patients with low CD4 lymphocyte counts (less than 50 cells/MUl or 200 cells/MUl depending on a trial. To choose therapy for patients with late-stage HIV infection is an intricate problem and requires an individual approach that will take into account not only the efficiency of therapy, but also its possible side effects, as well as potential drug interactions for the treatment of opportunistic infections. PMID- 26821430 TI - [The etiopathogenetic bases for antibacterial therapy and prevention of urinary tract infections]. AB - The paper discusses the pathogenesis of urinary tract infections, the mechanisms of resistance in their pathogens to antimicrobials and uroseptics, and approaches to defining patient management tactics. PMID- 26821431 TI - [Blood component donors and recipients as linked study objects in epidemiological population-based surveys]. AB - A population of hematological cancer patients as recipients of many blood components and that of donors of blood components and bone marrow are related to the common event of contamination with viruses of blood-borne infections; which occurs and is detectable during long-term treatment and follow-up. They share interaction traits and diverse communication mechanisms, which call for complex interrelated trials in both groups with a mandatory epidemiological evidenced based investigation of all cases of posttransfusion hepatitis B and/or C. The identity of infection with hepatitis B and C viruses, human immunodeficiency virus, and their association should be simultaneously studied in the populations of both donors and recipients of blood components and bone marrow. PMID- 26821432 TI - [Enteric microbiocenotic modifiers and ways of enhancing their efficacy]. AB - Efficient recovery of enteric microbiocenosis is one of the central problems not only in gastroenterology, but also in a number of related areas. This problem becomes particularly pressing after antibiotic treatment. The combined modifiers of enteric microbiocenosis are most effective among other symbiotic drugs. Bion-3 apart from symbionts contains a vitamin/mineral complex and acts as an adaptogen. PMID- 26821433 TI - Passage of 2015 Tort Reform Law Demonstrates the Effectiveness of Physician Advocacy! So What's Next in 2016? PMID- 26821434 TI - Fearless Forecast. PMID- 26821435 TI - Your Missouri Delegation Continues In Leadership Roles at the AMA Meeting. PMID- 26821436 TI - Advocacy Has Many Forms. PMID- 26821437 TI - The SGR Fix: Was It? PMID- 26821438 TI - The Money, Politics and Back Room Deals That Resulted in Obama Care: America's Bitter Pill. PMID- 26821439 TI - Manage False Claims Risk Before It's Too Late!. PMID- 26821440 TI - Defining Wellness as a Balance. PMID- 26821441 TI - The United States vs. the World. PMID- 26821442 TI - Unique Aspects of Sleep in Women. AB - Sleep in women differs in many respects from that of men. In general, women appear to report a greater need for sleep and more subjective complaints of non refreshing sleep than men. Sleep in women is affected at least partially by hormonal factors, with women typically suffering from sleep disturbance in connection with the menstrual cycle, pregnancy, and menopause Menstrual cycles are associated with prominent changes in reproductive hormones that may influence sleep. Sleep apnea and restless legs syndrome may be aggravated by pregnancy. Women may also develop insomnia during pregnancy, childbirth and menopause. PMID- 26821443 TI - Opiate Analgesics and the Perioperative Management of Patients with Obstructive Sleep Apnea. AB - As the rate of obesity and subsequently obstructive sleep apnea (OSA) continue to rise in North America and prescriptions for narcotic analgesics number in the tens of millions, it has become increasingly important to understand the interaction between OSA and opiate analgesics. Understanding the mechanism of action of opiate analgesics and the pathophysiology of OSA can help medical professionals understand the unique risks associated with pain management in this population of patients. PMID- 26821444 TI - Vaginal Hysterectomy: The Present Past. PMID- 26821445 TI - Secondary Use of Clinical Data to Enable Data-Driven Translational Science with Trustworthy Access Management. AB - University of Missouri (MU) Health Care produces a large amount of digitized clinical data that can be used in clinical and translational research for cohort identification, retrospective data analysis, feasibility study, and hypothesis generation. In this article, the implementation of an integrated clinical research data repository is discussed. We developed trustworthy access-management protocol for providing access to both clinically relevant data and protected health information. As of September 2014, the database contains approximately 400,000 patients and 82 million observations; and is growing daily. The system will facilitate the secondary use of electronic health record (EHR) data at MU to promote data-driven clinical and translational research, in turn enabling better healthcare through research. PMID- 26821446 TI - When Clinical Practice Guidelines And Clinical Practice Diverge. PMID- 26821447 TI - The Effect of Implementing a Comprehensive Unit-Based Safety Program on Urinary Catheter Use. AB - The goal of this performance improvement study was to evaluate the effect of a targeted intervention to decrease catheter-associated urinary tract infections (CAUTIs) and urinary catheter utilization by implementing quality improvement initiatives. Monthly patient data were abstracted including total CAUTI, urinary catheter utilization, urinary catheter days, CAUTI rate, and limited demographics for those with CAUTI, including age, sex, and diagnoses pre- and post intervention. The effect of CUSP on catheter utilization and CAUTI was determined using independent samples, t-tests and Mann-Whitney U tests. Implementing CUSP resulted in decreased catheter utilization from 89% to 75% (p = 0.001) and clinical reduction rate of CAUTI rate by 19% (from 7.9 to 7.2). Inappropriate urinary catheters can be avoided by daily assessment of catheter need and catheter removal. It is also important to establish catheter care guidelines and assure this care is being properly carried out. These management strategies ban decrease catheter utilization and preventable complications, such as CAUTI. PMID- 26821448 TI - Pre-Operative Education Classes Prior to Robotic Prostatectomy Benefit Both Patients and Clinicians. AB - As part of a process improvement initiative, we designed, implemented, and assessed the impact of pre-surgical education classes for patients scheduled to undergo robotic prostatectomy. Our aim was to both enhance patient access to important procedural information related to their surgery, and also limit the need for the repeated dissemination of information during patient calls to the office. PMID- 26821449 TI - Improving Access to Adjuvant Intravesical Therapy for Non-Muscle Invasive Bladder Cancer in a Community Hospital. AB - Relative to the high incidence of bladder cancer in Connecticut, an analysis of practice patterns in treatment of early stage bladder cancer was undertaken in a 275-bed community hospital, to determine if the practice patterns mirrored National Comprehensive Cancer Network guidelines. A nurse-led performance improvement project followed. Subsequently change in bladder cancer recurrence rates related to change in practice patterns was assessed. PMID- 26821450 TI - Improving Quality by Taking Aim at Incontinence-Associated Dermatitis in Hospitalized Adults. AB - A practice-improvement project was launched to implement an evidence-based intervention bundle for incontinence-associated dermatitis (IAD) and evaluate its impact on the identification, prevention, and management of IAD in hospitalized adults. PMID- 26821451 TI - Discharge Time Out: An Innovative Nurse-Driven Protocol for Medication Reconciliation. AB - An innovative method for discharge medication reconciliation was developed by nurses to ensure safe transition of care and improved patient outcomes. The discharge time-out process has empowered nurses to take a more active role in discharging their patients, and has fostered a more collaborative relationship between nurses and physicians. PMID- 26821452 TI - A Longitudinal Look at Nurses. PMID- 26821453 TI - Endovascular Aortic Repair of Primary Adult Coarctation: Implications and Challenges for Postoperative Nursing. AB - Endovascular aortic repair is a relatively new surgical technique used to treat a variety of aortic pathologies. Aortic coarctation traditionally has been managed with open surgical repair, involving a large posterolateral thoracotomy, cardiopulmonary bypass, and replacement of the narrowed section of the aorta with a dacron graft. Recent advances in minimally invasive aortic surgery have allowed for repair of the diseased section with an endovascular stent placed percutaneously through the groin under intraoperative fluoroscopic guidance. In this paper, the authors willfocus on the implicationsfor postoperative nursing care after endovascular repair of aortic coarctation using a case study of a 17 year-old male. This novel technique required education of the health care team with respect to implications for practice, understanding potential complications, discharge planning and follow-up. With any new surgical technique there are many questions and challenges that health care professionals raise. The main concerns expressed from the health care team stemmed from a lack of understanding of the disease pathology, and the different risk profile associated with an endovascular repair in contrast to an open repair. The authors will address these concerns in detail. PMID- 26821454 TI - [Description of the profiles of high consumers of a central emergency hospital specializing in cardiology and implementation of a nurse's intervention to optimize the care pathway]. PMID- 26821455 TI - [Organization of rehabilitation and treatment measures in the armed forces of foreign countries]. AB - The authors present an analysis of current state of rehabilitation and treatment system in the armed forces of foreign countries, and main directions of its development. The authors summarize an experience in the field of organization and carrying out of rehabilitation and treatment measures in the armed forces of foreign countries, and also define possible ways of how to apply gained experience in organizing sanatorium-resort provision for servicemen of Armed Forces of the Russian Federation. PMID- 26821456 TI - [Scoring of severity of patients' condition with acute surgical diseases and injuries of the abdominal cavity]. AB - Ten of the most frequent symptoms that do not require special methods of their determination except general clinical examinations established by any health care professional on pre-hospital stage were determined on the basis of analysis of more than one thousand records of patients with acute surgical abdominal diseases and clinical symptom load. The authors performed an assessment of each symptom depending on severity of patient's condition ranging from 1 point (satisfactory condition) till 5 points (critical condition). Information has been obtained: in case of satisfactory condition--up to 10 points, moderate--up to 20 points, heavy -up to 30 points, extremely heavy condition--up to 45 points and terminal condition--more than 45 points. Thus, conditional descriptive method of assessment of patient's condition during the clinical examination is combined with objective-scoring. The given method combines numeric expression with methods accepted in literature--"MFS-CA", "APACHE II" and allows to perform an objective assessment of the treatment process at different stages, to practice health care standards, to perform an analysis of outcomes. The article provides tables, which substantiate proposed method. PMID- 26821457 TI - [Burnout syndrome: diagnosis, principles of treatment, prophylaxis]. AB - Burnout syndrome is a socio-psychological phenomenon of emotional, motivational, and physical exhaustion as a result of chronic occupational stress. It is manifested as long-term emotional exhaustion, depersonalization and diminished personal and professional achievements. Burnout syndrome is common among health care workers, 'due to their high dedication, empathy for suffering patients, and decision-making related to life and health of patients. Personal, role and organizational factors influence on development of burnout. The clinical picture of burnout is multifactorial and can be described as a set of psychosomatic and somatic disorders, symptoms of social dysfunction. Diversity and non-specific symptoms of burnout syndrome determine the need for an interdisciplinary approach to its diagnosis. The leading role in solving problems related to stress and emotional burnout plays psychotherapy. The paper presents diagnostic criteria, risk factors, and methods of prevention and treatment of emotional burnout. PMID- 26821458 TI - [Staging rehabilitation of patients with spinal cord injuries in the Saki central military clinical resort after N.I.Pirogov]. AB - Medical rehabilitation of patients with spinal cord injuries is an actual problem of modern medicine, which is associated with increased number of victims injured in road and domestic accidents, high rate of disability, and necessity for a long term rehabilitation. An analysis of treatment of 386 patients with spinal cord injury in a specialized spinal center, Saki military resort is given in the article. PMID- 26821459 TI - [Medical devices and its in-field use]. AB - The quality of in-field treatment and prevention measures depends on the availability of modern medical devices, instruments, and equipment. In this regard peculiarities of medical care delivery during military conflicts advance special requirements for medical equipment, which is used by the medical service of the Armed Forces of the Russian Federation. The article shows prospects of in field use of the most important samples of medical devices adopted by the Armed Forces. PMID- 26821460 TI - [The 442th military clnical hospital celebrates 180th anniversary]. AB - The Hospital made a great contribution to the development of national healthcare during its 180-years history. Outstanding medical scientists of XIX-XX centuries, such as Bekhterev, Sklifosovsky, Vreden, Kupriyanov, Petrov and many others stood not only behind the history of the Hospital, they represented scientific society of military medical science. The merit of the Hospital cannot be overestimated during the World War II period, when 82% of the wounded and sick soldiers were returned to duty. The Hospital is considered as one of the best hospitals in the medical service of the Western Military District of the Russian Federation. Despite the on-going reconstruction of the main building, the year of 2014 has been eventful--institutional personnel achieved positive progress in improving combat skills and field training in the sphere of medical support in the district. Nowadays the methods of tutoring seminars with all categories of personnel are actively being improved. Currently 442th Military clinical hospital of Russian Defense Ministry is in the process of acquisition of its modern appearance. Phased plan for reconstruction and capital construction of its main building is now successfully implementing. PMID- 26821461 TI - [The past and future of surgical clinics of the Mikhailovsky clinical hospital ("Willie Hospital") of the Kirov Military medical academy]. AB - A brief 140-years history of the Mikhailovsky clinical hospital ("Willie Hospital") of the Kirov Military Medical Academy is presented. Today the department of military surgery, integrated into the system of emergency medical care, locates in historical building of the Kirov Military Medical Academy, and considered as part of multi-field regional center for the treatment of severe combined injuries, and is the only one injury care center of the first level in the Ministry of Defence of the Russian Federation. The hospital admits on treatment more that one million of severe injured patients annually; many patients with severe injuries are transferred from other regional hospitals. Every year more than two thousands of surgical interventions are performed in the hospital. Next renovation of the building is planned in the near future; it should provide further development of new medical technologies in the Kirov Military Medical Academy. PMID- 26821462 TI - [Stages of development of flight medical expertise in Russia]. AB - Flight medical expertise (FME) in military aviation is one of the most important areas of medical support of flight crews manning, maintaining of aircrew health and flight safety. The authors analyse the main stages of development of this area of medical practice. The priority in creation of FME system belongs to our country. Domestic scientists, prominent organizers of military medicine and a large group of aviation physicians developed organizational and methodological basis for studying different impacts of flight factors on the health of flight personnel, development of criteria for admission to flight operations, principles of organization of the examination, implementation of effective methods of disease diagnosis. At the present stage FME development is determined by the needs of medical, technical and psycho-physiological support of supersonic aircraft, the need to adjust to the requirements of aircrew health, advanced diagnostics of the functional state and the search for means to improve the stability of his body to flight factors. The main principles of the FME remains the complexity of the study of the human body in terms of its professional and individual approach to a medical examination, a thorough clinical, clinical and physiological and psychological examinations, regular medical supervision of the health of flight crews. PMID- 26821463 TI - ["The imperishable significance of the Soviet military medicine experience- in the Great Patriotic War..."]. PMID- 26821464 TI - [Development of guidance for the approval process of brand-new medical products and regenerative medicine products]. AB - Ministry of Health, Labour and Weltare has been conducting development of guidance for the approval process of brand-new medical products/development of guidance for medical devices in collaboration with Ministry of Economy, Trade and Industry as part of measures to promote practical use of brand-new medical products since 2005. The objective of this project is to expedite the processes from developmental process of medical devices to approval review and to introduce the medical devices to medical front quickly.. Ministry of Health, Labour and Welfare side has been making guidance for the guide in approval process of brand new medical products and regeneration medicine products to aim at acceleration and facilitation of development and approval process of innovative medical products. Twenty-two of the guidance have been issued as director of the evaluation and licensing division. The evaluation index about safety and efficacy required for medical devices and regenerative medicine products in progress were put together in these guidance and useful for medical devices developer to understand the point at the approved review. Therefore, I think that the evaluation index could also contribute to the efficient product development. The guidance about implantable artificial heart is issued as the representative example which was useful in the approved review. PMID- 26821465 TI - [FADCC in NIHS for prior consultation system of application of food additives]. AB - An increasing number of inquiries about application of food additives have been made from businesses in and outside Japan. The Ministry of Health, Labour and Welfare (MHLW) is requested to expedite the procedure for designation and revision of use standards. In June 2014, the MHLW set up a center for consultation on application concerning food additives (Food Additive Designation Consultation Center, FADCC) in the National Institute of Health Sciences, aiming to smoothly and expeditiously handle clerical work for designation or revision of the use standards. FADCC gives advice on how to prepare documents on the information such as physicochemical characteristics, effectiveness, safety, daily intake and use standards, based on actual cases and experience. PMID- 26821467 TI - [Biomechanism-based innovation of toxicology by the fundamental concept of "Signal Toxicity"]. AB - When Rachel Carson wrote the "Silent Spring" in 1962, the toxicology society was influenced in an indirect way mainly on environmental effects of massive use of pesticides. However, at that time, for those who were studying DDT and other pesticides, the biological effect of such chemicals were understood as a result of their long-lasting toxicants with slow elimination rates from the body; bio- persistency and in some case bio- and environmentally accumulative. And the chronic effects became overt including complex endpoints not only liver toxicity but, reproductive, immune, and neuronal. The impact of Silent Spring on toxicology seems to have established the foundations for scientifically accepting the problems widely raised by the Theo Colborn's "Our stolen future", although its main target was reproductive mechanisms including oestrogen and androgen system. For basic receptor biologists, non-monotonic dose-response curve was a matter of course, but for toxicologists at tnat time, all dose-response curves should be monotonic. With further detailed discussion many toxicologists started to understand that there is a good plausibility that such non-monotonic and low dose effect can happen in wild life and may be in humans under certain conditions. Since then, many toxicologists including us have initiated research on the so-called endocrine disrupting chemicals under new paradigm of receptor mediated- or signal-toxicity. To handle this problem, it became clearer that toxicology has to be innovated towards more biologically mechanistic science. This thinking has linked to the trend of toxicogenomics, where classical pathological findings are used to confirm the results of comprehensive mechanistic analysis data. In contrast our idea of toxicogenomics, designated as Percellome Toxicogenomics Project, was to develop comprehensive and quantitative gene expression networks out of transcriptomic data alone. Existing biological knowledge is used to help understand the biological or toxicological meaning of the generated networks. As a whole, the author would like to outline the strategies to cope with the new paradigms and to combine them to construct a more robust toxicological research system under the concept of "signal toxicity". We believe that this activity should contribute to the development of more comprehensive, faster, cheaper (including less animal to use), and reliable system for the identification, and prediction of toxicity for any kind of agents entering our body and environment. PMID- 26821466 TI - [Leukoderma caused by chemicals: mechanisms underlying 4-alkyl/aryl-substituted phenols- and rhododendrol-induced melanocyte loss]. AB - Chemical leukoderma is a skin depigmentation disorder known to occur in manufactural workplace through contact with chemicals, such as monobenzyl ether of hydroquinone (MBEH) and 4-tert- butylphenol (4-TBP). In the skin depigmented legions induced by these chemicals, the number of melanocyte was severely decreased. Anti-melanoma agent 4-cysteaminylphenol (4-SCAP) and its derivatives are also known to cause leukoderma. Evidence has accumulated supporting that typical class of chemicals causing leukoderma is "4-alkyl/aryl-substituted phenols/catechols", which are structurally similar to melanin precursor tyrosine. Tyrosinase-mediated oxidation of these chemicals yields toxic ortho-quinones which bind to cellular proteins and produce reactive oxygen species. Accordingly, this tyrosinase-dependent metabolic activation is thought to cause melanocyte specific damage and subsequent immune reactions toward melanocytes. Recently, rhododendrol, an inhibitor of tyrosinase developed for so-called lightening/whitening cosmetics, was shown to cause leukoderma in the users. In this review, I document the causes of known chemical leukoderma and rhododendrol- induced leukoderma, focusing on their common mechanisms underlying melanocyte loss. PMID- 26821469 TI - Particle size distribution of aerosols sprayed from household hand-pump sprays containing fluorine-based and silicone-based compounds. AB - Japan has published safety guideline on waterproof aerosol sprays. Furthermore, the Aerosol Industry Association of Japan has adopted voluntary regulations on waterproof aerosol sprays. Aerosol particles of diameter less than 10 um are considered as "fine particles". In order to avoid acute lung injury, this size fraction should account for less than 0.6% of the sprayed aerosol particles. In contrast, the particle size distribution of aerosols released by hand-pump sprays containing fluorine-based or silicone-based compounds have not been investigated in Japan. Thus, the present study investigated the aerosol particle size distribution of 16 household hand-pump sprays. In 4 samples, the ratio of fine particles in aerosols exceeded 0.6%. This study confirmed that several hand-pump sprays available in the Japanese market can spray fine particles. Since the hand pump sprays use water as a solvent and their ingredients may be more hydrophilic than those of aerosol sprays, the concepts related to the safety of aerosol sprays do not apply to the hand pump sprays. Therefore, it may be required for the hand-pump spray to develop a suitable method for evaluating the toxicity and to establish the safety guideline. PMID- 26821468 TI - [Polyploidy induction by spherical size standard polystyrene particles in a Chinese hamster cell line CHL]. AB - To investigate relationships between particle (as a model of aggregates) size in a nanomaterial test suspension and its cytotoxicity, a series of eleven sizes of polystyrene (PS) particles were tested in the cytotoxicity test and the chromosome aberration test by using a Chinese hamster cell line CHL. The PS particles were spheres with defined diameters ranging from 0.1 to 9.2 um. A series of eight sizes of particles with diameters ranging from 0.92 to 4.45 um showed stronger cytotoxicity than the others. There was a marked difference in cytotoxicity between the 4.45- and 5.26-um particles. The 0.92- to 4.45-um particles did not induce structural chromosome aberrations but induced a high frequency of polyploidy in the chromosome aberration test. The 5.26-um particles showed very weak induction of polyploidy. The incorporation of the 4.45-um particles into CHL cells was observed by scanning electron microscopy (SEM). Some cells incorporated more than 10 particles. The semi-quantitative measurement of incorporation of particles into cells was performed by flow cytometry with a parameter of side scattered light (SSC) intensity. It showed that CHL cells preferably incorporated the 4.45-um particles to the 5.26-um particles. These findings suggest that CHL cells may have a kind of size-recognition ability and incorporate a particular size of particles. The particles may prevent a normal cytokinesis resulting in polyploidy induction. Nanomaterials also may show size dependent toxicity. Data on particle (or aggregate) size distribution in the test suspension should be provided to evaluate properly the results of toxicity tests of nanomaterials. PMID- 26821470 TI - Summary information of human health hazard assessment of existing chemical substances (I). AB - Under the Chemical Substances Control Law (CSCL) in Japan, initial hazard information tor existing chemical substances has been collected by the Ministry of Health, Labour and Welfare, Japan (MHLW) to assess potential initial risks to human health. We have reviewed all collected toxicity information pertaining to acute toxicity, repeated dose toxicity, genotoxicity, and/or reproductive/developmental toxicity and performed hazard assessments. Approximately 150 substances are currently undergoing review and assessment. For clarification and evaluation of each toxicity study, we have created a dossier (a collection of study data containing a detailed summary of the methods, results, and conclusions of each study) in English using the International Uniform Chemical Information Database (IUCLID) version 5. The IUCLID dossier format is widely used and has been accepted as one of the most beneficial formats for providing summarized chemical substance toxicity assessments. In this report, as a contribution to our ongoing hazard assessment activity, we present summary hazard information related to the potential human health effects of the following 5 chemical substances: 4-chlorobenzoyl chloride (CAS: 122-01-0); benzenesulfonic acid, 4-hydroxy-, tin (2+) salt (CAS: 70974- 33-3); chlorocyclohexane (CAS: 542 18-7); 1,3-cyclohexanedimethanamine (CAS: 2579-20-6); and 1,3,5-triazine-2,4,6 (1H,3H,5H) -trithione (CAS: 638-16-4). The IUCLID dossiers created for these 5 chemical substances will be made available via the Japan Existing Chemical Data Base (JECDB) at . Additional human health hazard information on existing chemical substances will be provided using the same methodology and website when it is available. PMID- 26821471 TI - [Expression of SFRP5 mRNA in Rat Skeletal Muscle after Contusion]. AB - OBJECTIVE: To investigate the relationship between the expression of secreted frizzled-related protein 5 (SFRP5) mRNA and the time interval after skeletal muscle injury in rats by real-time PCR. METHODS: A total of ninety SD rats were randomly divided into the contusion groups at different times including 4h, 8h, 12h, 16h, 20h, 24h, 28h, 32h, 36h, 40h, 44h, 48h after contusion, incision groups at different times including 4h and 8h after incision and the control group. The samples were taken from the contused zone at different time points. The total RNA was isolated from the samples and reversely transcribed to analyze the expression levels of SFRP5 mRNA. RESULTS: Compared to the control group, the expression of SFRP5 mRNA in contusion groups were down-regulated within 48 h after contusion and reached the lowest level at 20 h, and the expression of SFRP5 mRNA gradually increased from 20 h to 48 h after contusion. The expression of SFRP5 mRNA in the incised groups were significantly lower than that of the contusion groups at 4 h after injury. At the time of 8 h, the expression levels between the contusion and incision groups showed no statistically significant difference. CONCLUSION: It is suggested that SFRP5 mRNA analysis may show regular expression and can be a marker for estimation of skeletal muscle injury age. PMID- 26821472 TI - [Serum IgE in Guinea Pigs Died of Anaphylactic Shock and Its Forensic Signifi- cance When the Guinea Pig Cannot be Timely Refrigerated]. AB - OBJECTIVE: To investigate the serum IgE with various postmortem intervals (PMI) in guinea pigs due to sudden death from anaphylactic shock and to explore the effect of refrigeration of corpse on serum IgE level and its application value in forensic medicine. METHODS: The animal death models of anaphylactic shock were established. The corpses were preserved at room temperature (20 degrees C ) for 6 h and then refrigerated at 4 degrees C. The serum was sampled at 6, 12, 24, 36 and 48 hours after death. The IgE level of serum was detected with ELISA. The control group was also established. RESULTS: The serum IgE level had significant. difference between the experimental group and the control group (P < 0.05). There was no significant difference among the experimental groups at 6, 12, 24, 36 and 48 hours post- mortem (P > 0.05). CONCLUSION: If the corpses were placed in 4 degrees C conditions 6 hours after anaphylactic death, the serum IgE still shows a good marker within 48 h for forensic investigation. PMID- 26821473 TI - Karoshi Related to Labor Intensity and Risk of Cardiovascular Events: A Case Report. AB - Karoshi remains one of the most troublesome issues in forensic identification. It is rather a social medicine than a clinical disease. Japanese scholars pioneered examining the relation between sud- den cardiac death (SCD) and chronic fatigue from long time and/or high-tension work. In the current case, a 55-year-old man, whose job was loading and carrying heavy cement bags, was found dead after 11 days of continuous hard work. His family members sued the cement factory for his death and claimed for compensation. The problem was the difficulty of identifying the causative relation without the precedent or the relevant regulations. However, the forensic problems were finally acknowledged after autopsy and calculation of labor intensity. The lawsuit was won as the first case pertaining to Karoshi in the Chinese court. PMID- 26821474 TI - [Distribution of Inflammatory Cells and Expression of PSGL-1 in Infant Brainstem Tissue Related Fatal Brainstem Encephalitis]. AB - OBJECTIVE: To explore the distribution of inflammatory cells and positive expression of P-se- lectin glycoprotein ligand-1 (PSGL-1) in infant brainstem tissue from hand-foot-mouth disease related fatal brainstem encephalitis. METHODS: Twenty brainstem samples from infants suffered from brainstem en- cephalitis were collected as the experimental group. Ten brainstem samples from infants died of non- brain diseases and injuries were collected as the control group. The distribution of inflammatory cells and the expression of PSGL-1 in the two groups were examined by immunohistochemical method. The characteristics of the positive cells were observed. RESULTS: In brainstem tissue of the experimental group, there were sleeve infiltrations of inflammatory cells around the vessels and in the glial nodule. Microglia was the most and following was neutrophils around the vessels and in the glial nodule. There was a significant statistical difference among microglias, neutrophils and lymphocytes (P < 0.05). There was no sleeve infiltration in the control group. PSGL-1 protein was expressed widely in inflammatory cells in the experimental group, especially in the inflammatory cells around the vessels and in the glial nodule. But PSGL-1 positive staining could be observed significantly less in the control group comparing with the experimental group (P < 0.05). CONCLUSION: Microglia is the main type of inflammatory cells involved in the progress of the fatal disease. Moreover, PSGL-1 could participate in the pathogenesis of hand-foot-mouth disease related fatal brainstem encephalitis. PMID- 26821475 TI - [Application of Ocular Trauma Score in Mechanical Ocular Injury in Forensic Medicine]. AB - OBJECTIVE: To evaluate the application value for the prognosis of mechanical ocular injury cases using ocular trauma score (OTS). METHODS: Four hundred and eleven cases of mechanical ocular trauma were retrospectively reviewed. Of the 449 eyes, there were 317 closed globe injury and 132 open globe injury. OTS variables included numerical values as initial visual acuity, rupture, endophthalmitis, perforat- ing or penetrating injury, retinal detachment and relative afferent pupillary block. The differences be- tween the distribution of the final visual acuity and the probability of standard final visual acuity were compared to analyze the correlation between OTS category and final visual acuity. The different types of ocular trauma were compared. RESULTS: Compared with the distribution of final visual acuity in standard OTS score, the ratio in OTS-3 category was statistically different in present study, and no differences were found in other categories. Final visual acuity showed a great linear correlation with OTS category (r = 0.71) and total score (r = 0.73). Compared with closed globe injury, open globe injury was generally associated with lower total score and poorer prognosis. Rupture injury had poorer prognosis compared with penetrating injury. CONCLUSION: The use of OTS for the patients with ocular trauma can provide re- liable information for the evaluation of prognosis in forensic medicine. PMID- 26821476 TI - [Assessment of Function of a Single Limb after Injury]. AB - OBJECTIVE: To explore the method for the objective evaluation of single limb function after in- jury in forensic medical practice. METHODS: The score of activities of daily living (ADL) were graded for a single limb function after injury from 47 cases. All cases were simultaneously evaluated using the different methods including Fugl-Meyer motor function assessment (FMA), weighting, look-up table (LUT). The correlation were compared between ADL and the other three methods. RESULTS: Injured part and the score using the three methods were correlated with ADL score (P < 0.05). The correlation coeffi- cient (|r| value) showed highest using LUT method, and lowest using FMA method. CONCLUSION: The loss function of limb is affected by the injuried parts. The methods of FMA, weighting and LUT show a good accuracy for evaluating the limb function after injury and the correlation presents higher using LUT method. PMID- 26821477 TI - [Palm Area as a Ratio of Body Surface Area in Chinese Adult Male Population]. AB - OBJECTIVE: To analyze palm ratio of body surface area (BSA) based on the body different surface area formula. METHODS: Forty-four Chinese adult males were selected in this study. The contour of left single palm was recorded and the palm area was calculated by cut-paper weighing method. The body surface was calculated by the height and weight based on 12 formulas of body surface area. Then, the palm ratio of BSA was calculated. RESULTS: The average palm ratio of BSA was (0.789 +/- 0.075)%. The data showed statistically significant difference compared with the traditional ratio (1%) (P < 0.05). CONCLUSION: The ratio of BSA in Chinese adult male population showed more accuracy compared with the traditional ratio in this present study. The forensic evaluation can be affected by using the different ratio of BSA. PMID- 26821478 TI - [Forensic Analysis of 33 Cases of Fatal Pulmonary Thromboembolism]. AB - OBJECTIVE: To explore the related risk facts of pulmonary thromboembolism (PTE) and analyze the relation between PTE and the trauma or medical behavior by investigating the cases of PTE. METHODS: Thirty-three cases were selected from Institute of Forensic Science (IFS) from 2000 to 2014. RESULTS: In 33 cases, 16 decedents were male, 17 decedents were female; different degrees of dyspnea, chest tight- ness and syncope symptoms were the clinical manifestation of the deceased; the thrombus was mainly distributed in the left and right pulmonary arteries. The main source of embolism was the deep vein of lower limb and the left probability was higher. Trauma, limited position, operation and cardiovascular disease showed high-risk factors of PTE; D-Dimer test, hemolytic test and computer tomography pul- monary angiography were the diagnostic tools for PTE. In some cases, trauma and medical malpractice could be involved in the cause of death. CONCLUSION: Non-typical clinical symptoms present in the most cases caused by PTE, and these cases always show many high-risk factors. The relation between PTE and injury or medical behavior should be considered carefully in the forensic pathological practice. PMID- 26821479 TI - [Analysis of 105 Incarcerated Inmate's Death]. AB - OBJECTIVE: To analyze the characteristics in the incarcerated inmate's death, investigate the main cause of death of the incarcerated inmate and provide some information for forensic investigation. METHODS: The cases from the forensic medical center of Shanxi Medical University from 2005 to 2013 were selected. The statistical analysis was performed by using the incarcerated inmate's gender, age, cause of death, manner of death, and disease as the markers. RESULTS: There were 100 men, 5 women in the 105 incarcerated inmates; the age range was from 16 to 65 years; Inmates were mostly died of natural diseases, mainly in the respiratory and cardiovascular diseases; the main unnatural death was suicide with a rate of 54.5%. CONCLUSION: At present, most incarcerated inmate's death are due to natural diseases. The prison should improve incarcerated inmate's lives, work and health care conditions, and strengthen supervision of law enforcement. PMID- 26821480 TI - Forensic Medical Assessment for Neurologic Erectile Dysfunction: 58 Case Reports. AB - To introduce the approaches and procedures of neurologic erectile dysfunction (ED) assessment in our institute, and evaluate the neurologic investigation by making an analysis of 58 cases. Diagnostic criteria of neurologic ED: nervous system injuries or diseases, abnormal clinical symptoms and signs, electrophysiological abnormalities of nervous system, abnormal results of nocturnal penile tumescence and rigidity (NPTR) (penis rigidity <60% and lasting time <10 minutes). In the group of 20 patients with the injuries of the brain, spinal cord or spinal root nerves, pudendal cortical somatic evoked potential (PCSEP), sacral reflex latency (SRL), pudendal-to-cortical motor evoked potential (PCMEP), penile sym- pathetic skin responses (PSSR) and NPTR showed abnormality by 45%, 20%, 20%, 85% and 85%, re- spectively. In 38 patients with the injuries of pelvic fracture with urethra break, PCSEP, SRL, PCMEP, PSSR and NPTR showed abnormality by 24%, 5%, 20%, 92% and 66%, respectively. In the former, 35% were identified to have severe ED, and 50%, moderate ED; in the latter, 21%, to have severe ED, 13%, medium ED, and 37%, light ED. The approaches and procedures were proved to possess excellent specificity and reliability in the assessment of neurological ED. PMID- 26821481 TI - [Development of a Forensic Multiplex Amplification STR Kit for 15 Autosomal STR Loci and 10 Y-STR Loci]. AB - OBJECTIVE: To establish a multiplex STR genotyping method for autosomal STR and Y STR loci in forensic biological practice. METHODS: Widely used autosomal STR loci and Y-STR loci were selected. A set of PCR primers was designed, and a 5-dye fluorescent labeled STR multiplex PCR reagent kit was developed. RESULTS: A kit was developed which can simultaneously detect 15 autosomal STR loci, 10 Y-STR loci, and an Amelogenin. CONCLUSION: The 15 autosomal STR plus 10 Y-STR kit in combination with capillary electrophoresis method was used to STR genotyping with accurate and reliable results. The new one-step testing kit can potentially be widely used in forensic cases and DNA databank in the future. PMID- 26821482 TI - [Progress in Stress Cardiomyopathy and Its Forensic Application]. AB - Stress cardiomyopathy is an atypical myocardial disease induced by emotional or physical stress, with the characteristic of left ventricular systolic dysfunction, transient imaging and electrocardiogram (ECG) changes. Sudden cardiac death can occur in severe cases. Clinical symptoms are likely to appear on acute myocardial infarction, but the exact pathological mechanism is unclear. In the present study, we perform a systematic review of the literature on the clinical manifestations, epidemiological characteristics, ECG, imaging and laboratory tests of stress cardiomyopathy, in order to provide the values for forensic pathology diagnosis. PMID- 26821483 TI - [Progress in Association between Genetic Correlation and Human Violent Behavior]. AB - Human violent behavior is a complex behavior which is influenced by genetic and environmental factors. There is a trend in investigating the mechanism of violent behavior by using the genetic methods. This article reviews several candidate genes and advances in epigenetics which are associated with violent behavior. The prospects and significance of violent behavior research from the view of gene polymorphism and epigenetics are also discussed. PMID- 26821484 TI - [Reviewer of scientific articles]. PMID- 26821485 TI - [Breastfeeding and non-communicable diseases later in life]. AB - Evidence is increasing that breastfeeding beyond its well-established beneficial effects during the breastfeeding period, also confers long-term benefits, particularly in the prevention of risk factors for non-communicable diseases. Therefore, we sought to identify the latest evidence about the benefits of breastfeeding later in life. We searched on PubMed for published studies assessing the effects of breastfeeding on risk factors for non-communicable diseases later in life (cardiovascular risk factors, obesity/overweight, type-2 diabetes and inflammation). Out of 75 references identified, 31 were included in this revision to review the available evidence on long-term benefits of breastfeeding. The search was completed on December 2014. Some of the reviewed studies suggest that breastfeeding may offer protection to develop risk factors for non-communicable diseases later in life, and also have been proposed several mechanisms for a protective effect of breastfeeding against non-communicable diseases. Although there is more evidence of overweight/obesity and cardiovascular disease these is inconclusive. There is a lack of evidence for type-2 diabetes and inflammation, therefore it is difficult to conclude. Although the majority of the studies are observational and this is a limitation to prove causality, the results of this article may provide support to breastfeeding policies. PMID- 26821486 TI - [Predictive capacity of anthropometric indeces in the detection of metabolic syndrome in Chilian adults]. AB - The presence of cardiometabolic components conditions the risk increase in the appearance of the metabolic syndrome and the associated pathologies. The insulin resistance is probably the subjacent mechanism to the complications derived from this syndrome, where the abdominal adipose accumulation is a common and f equent characteristic. The purpose of this study was to determine the predictive capability of the anthropometric estimating central adipose distribution indexes against the body mass index in the detection of the metabolic syndrome in Chilean adults. A descriptive crosssectional study was conducted on 229 adults, information obtained through a secondary database. There were analyzed through a Pearson correlation and receiver operating curves determining the area. under the curve. The results showed the predominance of 58.3% of the metabolic syndrome prevailed according to NCEP-ATP III, where the anthropometric indexes such as waist height index (0.746), waist circumference (0.735) and body mass index (0.722) didnot-show significant differences in the detection of the metabolic syndrome components. It did show a higher correlation of these cardiometabolic. factors with the waist height index and waist circumference. PMID- 26821487 TI - [Maternal Predictors of Body Mass Index of Pre-school and School Age Children]. AB - The objective was to identify maternal variables that could be used as predictors of the child's body mass index (BMI). We considered the following variables: (a) socio-demographic (age, education, occupation, marital status and family income); (b) anthropometric (BMI); and (c) upbringing strategies (monitoring and limits for eating habits, monitoring and sedentary behavior limits, discipline and control in feeding. A predictive correlational study was carried out with 537 dyads (mother-child). Children enrolled in 4 public schools (2 for pre-school children and 2 for primary school children) were selected for probabilistic, random sampling. The mothers answered the Feeding and Activity Upbringing Strategies Scale, giving socio-demographic information and the dyads' weight and height was measured. The data were analyzed for correlations and path analysis. It was found that the average age of mothers was 34.25 years (SD=6.91), with 12.40 years of education (SD=3.36), 53.3% mentioned that they were housewives and 46.7% had a paid job outside of the home; 38.5% showed pre-OB and 27.3% some degree of OB. The child's average age was 7.26 years (SD=2.46), and 3.2% showed low weight, 59.6% normal weight and 37.2% OW-0B. It was found that working outside the home, having a higher maternal BMI, less control and more discipline in feeding are variables that predict higher BMI in the child. We recommend the design of interventions to reduce and treat the child's OW-OB taking into account the predictors that were found. PMID- 26821488 TI - Percentile distribution of anthropometric variables in pregnant women. AB - Anthropometric indicators play an important role in the health status assessment of individuals and populations across the different vulnerable groups, due to which it is necessary to ascertain the percentile distribution of the weight, body mass index (BMI), and mid-arm, thigh, and calf circumferences in pregnant women for each week of gestational age. This descriptive and cross-sectional study included 4481 measurements of anthropometric variables obtained from 745 pregnancies out of 719 subjects aged between 19 and 39 years, who were well nourished, healthy, without clinical edema in the third trimester, with single pregnancy, and validated gestational age. All evaluations were conducted at the Centro de Atencion Nutricional Infantil Antimano, CANIA, from 1998 to 2012. The anthropometric measurements were performed by standardized anthropometrists. Measures of central tendency and dispersion, bivariate correlations, and percentiles 3, 10, 25, 50, 75, 90, and 97 were calculated for each gestational age, between the 8th and 37th weeks of gestation. The number of measurements performed for each studied variable ranged from a minimum of 101 and a maximum of 241 at each gestational week. The BMI and circumference behaviors showed increases as the gestational age advanced. The changes in the variables observed in the 50th percentile between weeks 8 thru 37 were: weight, 10.10 kg; BMI, 4.23 kg/m2; and circumferences (cm): mid-arm, 0.45; calf, 1.60; and thigh, 3.55. The results of this study provide the means to simplify the screening and follow-up of the nutritional status in an accurate manner at any stage of gestation until the 37th week. PMID- 26821489 TI - Percentile distribution for anthropometric variables used to estimate body composition in pregnant women. AB - Anthropometric indicators of body composition, reflective of fat and lean compartments in pregnant women, undergo changes throughout gestation. The adequate interpretation of these indicators requires the availability of percentile distribution values for each week of gestational age. The objective was to determine the percentile distribution for subcutaneous skin-fold thicknesses: biceps, triceps, subscapular, mid-thigh, and both arm fat and arm muscle areas for each week of gestational age. This descriptive and cross sectional study included 4,481 measurements of anthropometric variables obtained from 745 pregnancies out of 719 subjects aged between 19 and 39 years, well nourished, healthy, without clinical edema, single pregnancy, and validated gestational age. Evaluations were conducted at the Centro de Atencion Nutricional Infantil Antimano, between 1998 and 2012. The anthropometric measurements were performed by standardized anthropometrists. Descriptive statistics, bivariant correlations, and percentiles 3, 10, 25, 50, 75, 90, and 97 were calculated for each week of pregnancy between weeks 8 thru 37. The number of measurements performed for each variable studied at each week of gestation ranged between 100 and 236. The behavior of the variables reflecting the fat component showed increases as the gestational age advanced (1.86 cm2), whereas the muscle area showed decreases (-0.02 cm2). The most noticeable variations were seen in the subscapular and mid-thigh skin-fold thicknesses 2.90 mm and 5.0 mm, respectively. The availability of percentile distributions of the anthropometric variables used in the evaluation of body composition for pregnant women per gestational age, contributes to optimizing the nutritional categorization in this population group. PMID- 26821490 TI - Aflatoxin M1 in pasteurized, UHT milk and milk powder commercialized in Londrina, Brazil and estimation of exposure. AB - Aflatoxin M1 (AFM1) is found in milk and other excretion products after aflatoxin B1 intake. AFM1 is carcinogenic to humans, and known levels of dairy product contamination is important to understand the risks to which the population is exposed. The occurrence of AFM1 was evaluated in 42 milk samples commercialized in Londrina, Parana State, Brazil and this rate of occurrence was used to estimate this exposure. AFM1 determination was carried out by ELISA, and was detected in 100% samples at levels ranging from 0.01 to 0.81 microg/kg (mean 0.13 microg/kg). None of the samples presented AFM1 above the maximum permitted level by Brazilian Legislation (0.5 microg/kg for fluid milk and 5 microg/kg for milk powder). The estimated daily intake (EDI) of AFM1 was evaluated, and the average intake was 0.468 ng/kg body weight (b.w.) for adolescents, 0.384 ng/kg b.w. for adults and 0.559 ng/kg b.w. for the elderly. Values of EDI of AFM1 found in Londrina pose a toxicological risk to the population investigated. To the best of our knowledge, this is the first report on estimated AFM1 dietary exposure from Parana, Brazil. PMID- 26821491 TI - [Brazilian Food Composition Database (TBCA-USP): Data compilation to serve the public good]. AB - The article shows the evolution of the Brazilian Food Composition Database (TBCA USP), since its creation until its next update. The article characterizes the TBCA-USP database like a public good and highlights the importance of the food composition data compilation as a high cost-effective activity. It reports the social relevance of the information about food composition and the importance of this database in the national context. It also indicates extension and update strategies of the TBCA-USP. PMID- 26821492 TI - Sheep milk: physical-chemical characteristics and microbiological quality. AB - Sheep milk is the third most consumed milk in Brazil. It is much appreciated for its nutritional status and is important for children that have problems with cow milk. Little information is known about the chemical, physical and microbiological composition of sheep milk from South Brazil. Thus, the aim of this study was to describe chemical and microbiological characteristics of sheep milk produced on two rural properties located in southern Brazil (ParanA and Rio Grande do Sul). The chemical composition of sheep milk was 17.32 g/100 g total solids, 5.86 g/100 g total protein, 4.46 g/100 g casein, 1.08 g/100 g whey protein, 7.28 g/100 g fat, 0.93 g/100 g ash, and 3.41 g/100 g lactose. High somatic cell count (1.7x106 cells/mL), total mesophilic bacterias (16.0 x 106 CFU/mL) and psychrotrophics (5.8 x 106 CFU/mL) were observed. Growth of Staphylococcus aureus, enterobacteria and coliforms occurred in 100% of the samples, and 45% of the samples showed growth of Escherichia coli. The sheep milk physical-chemical and microbiology parameters are similar to those presented in the literature for other countries but somatic cell count presented high levels. PMID- 26821493 TI - [Orthorexia: A new challenge for health care professionals]. PMID- 26821494 TI - [Venom as a cure--some notes on ancient medicine]. AB - Very little is known today about the linguistics and facts relating to venoms in the ancient world. The article concerns itself initially with the terminology: How were venoms conceptualized and what position did they occupy among medicines and other poisons? Additionally ancient knowledge of the constitution and location of the venoms will be examined. Furthermore, it shall be outlined how it was perceived that the poisons actually took effect. The results of our investigations indicate that it was unlikely that venoms were used for medicinal purposes in ancient times. PMID- 26821495 TI - ["Psychological employees" in psychiatry. The establishment of clinical psychology at the example of Lilo Sullwolds diagnostic efforts to incipient schizophrenia]. AB - Lilo Sullwold (*1930) was the first psychologist in the German Federal Republic to acquire habilitation for Clinical Psychology at a Medical Faculty. However, she had already been appointed professor for Clinical Psychology following to a new University Act implementing the recommendations of the National Council of Science and Humanities. Her habilitation treatise to justify the initial professorship appointment centered on a self-made questionnaire as a diagnostic tool for beginning schizophrenia. The manner how the questionnaire together with the politico-scientific structural changes at the German Federal universities endowed the young psychologist with a carrier in psychiatry, is an illuminating example of psychology's way into psychiatry: the institutionalization and professionalization of Clinical Psychology in psychiatry since the end of the 1950s up to the end of the 1970s. In a comparative perspective on the developments of Clinical Psychology in the German Democratic Republic, the example demonstrates not only the role of new psychological theories und methods in research and clinic in enabling the entry of the new profession into psychiatry, but also the importance of initial socio-economic and socio-politic frame conditions and decisions. The negotiation of the scope or limits of competences between doctors and psychologists created more than a professional niche inside the clinic; it changed psychiatry and psychology as academic branches in their structures due to the establishment of new Clinical Psychology departments. The role of the psychologist turned from a doctor's "assistant" into a colleague at "eye level". PMID- 26821496 TI - [Karl Sudhoff and the Nobel Prize]. AB - Drawing on files in the Nobel Prize archive for Physiology or Medicine in Solna, Sweden, this paper illuminates the Nobel Prize nominations for and by Karl Sudhoff from 1918 to 1923. He was nominated by Max Cloetta and Max Neuburger, and Sudhoff himself put forward Julius Hirschberg, Erwin Payr and Georg Sticker. Even though none of the proposals led to a prize, the nomination letters offer insights in the relationships between leading historians of medicine in the immediate post-war years. The study is part of a project exploring the construction and enactment of scientific excellence. PMID- 26821497 TI - [RESISTANCE OF HCV TO NEW DIRECT ACTING ANTIVIRALS]. AB - Hepatitis C virus (HCV) is a leading cause of chronic viral hepatitis affecting 130-150 million people world-wide. HCV is an RNA virus of the Flaviviridae family, containing ~9600 nucleic acids coding for structural and nonstructural proteins, divided into 7 genotypes of which the most prevalent is genotype 1. The goal of HCV therapy is to achieve sustained virological response (SVR), currently defined as undetectable serum HCV RNA 12 weeks post-treatment. Treatment with the new direct acting antivirals (DAAs) that target the HCV protease NS3/4A, NS5A and the NS5B polymerase proteins can lead to more than 90% SVR. Successful treatment depends, among other factors, on the viral genotype and subtype and the barrier to resistance which depends on the number of mutations needed to cause drug resistance. To ensure effective treatment the HCV subtype should be determined prior to therapy. Resistance mutations that affect the new DAAs and are located in the three HCV drug target proteins have already been defined. The relevance of resistance testing in DAAs naive individuals is controversial, though current American Association for the Study of Liver Diseases (AASLD) guidelines do recommend testing for Q80K mutation in the NS3 protein prior to simeprevir therapy and for the L31V/A and Y93H/N mutations in the NS5A prior to daclatasvir therapy. In cases of DAAs treatment failure, though the European Association for the Study of the Liver (EASL) guidance is not conclusive, the new AASLD guidance recommends NS3/4A and NS5A resistance testing prior to retreatment. Collecting more data on the frequency of resistance mutations prior to DAAs therapy and following virological failure will assist in future retreatment planning and potential eradication of HCV. PMID- 26821498 TI - [LESSONS FROM PREPAREDNESS OF HOSPITALS TO SNOWSTORMS]. AB - Snowstorms are not a usual scene in Israel, which normally enjoys relatively warm weather, even in the winter. In the last two years we faced three severe snowstorms that had a major impact on the routine daily life in Israel. Roads were blocked, people experienced long electricity power failures, and secondary to slippery conditions, there was more than a threefold increase of orthopedic injuries. These storms confronted hospitals with unique challenges, both medical and logistic. Hospitals must be prepared to cope with the challenge of maintaining continuation of care. We propose four phases of preparedness strategy: at the beginning of the winter, once there is a weather forecast warning, during the storm itself, and returning to norm. This manuscript deals with the lessons learned by two hospitals in Safed and Jerusalem dealing with snowstorms. PMID- 26821499 TI - [BURNS IN ISRAEL: DEMOGRAPHIC, ETIOLOGIC AND CLINICAL FEATURES, 2004-2010]. AB - BACKGROUND: The treatment of burn patients plays a major role in the health system, requiring numerous resources and extensively long hospitalizations. The treatment involves Intensive Care Units and the entire medical and para-medical staff. Currently, Israel has 5 designated burn units, strategically scattered all over the country. Recently, due to some major burn disasters, reevaluation of the demography, etiology and clinical features of burns has been conducted. OBJECTIVES: The study entails quantity and quality evaluations of burn victims in Israel between the years 2004 and 2010, identification of high risk populations and recent demographic, etiological and clinical trends. METHODS: A data analysis was conducted of all the burn patients hospitalized in Israel's 5 trauma centers' burn units between the years 2004 and 2010 according to the Israeli Trauma Registry (ITR). RESULTS: Between the years 2004 and 2010, 5270 burn victims were hospitalized in five trauma centers burn units. The average hospitalization period was 11.67 days, while the mortality rate was 3.72%. High risk populations were identified as babies up to 2 years old and the non-Jewish population. DISCUSSION: High risk populations were identified, such as young babies and the non-Jewish population. These groups should be addressed specifically with proper publicity and information. Even though mortality rates were stable, the mean hospitalization length is declining over the years, possibly secondary to advanced dressing and ambulatory treatments. PMID- 26821500 TI - [INCREASED MORTALITY OF DELAYED PATIENTS IN THE EMERGENCY DEPARTMENT OF A TERTIARY MEDICAL CENTER]. AB - INTRODUCTION: Boarding patients awaiting hospitalization in the emergency department increases mortality and complications, and stands in contrast to the recommendations of emergency medicine associations worldwide. Although Israel's Ministry of Health and the media are addressing the issue, boarding patients in emergency departments is common in hospitals throughout the country. There are no current studies that assess the influence of boarding in emergency departments on the patient's mortality and hospitalization. In 2011, a decision was made in our hospital to board patients in a separate section of the emergency department due to the lack of beds in the inpatient wards. AIMS: This study aimed to demonstrate the scale of boarding patients in a tertiary hospital in Israel and its influence on mortality and length of hospitalization. We examine effects of a deliberate boarding policy on mortality and describe the boarding phenomena, and its causes, to Israeli physicians. STUDY METHODS: This is a retrospective study, comparing patients hospitalized through the emergency department to internal medicine wards in a tertiary hospital during three consecutive years, and studying the effects of deliberate boarding policy in the emergency department on mortality and length of stay [LOS] in the hospital. RESULTS: Roughly half the patients stayed in the emergency department for more than 10 hours. The mortality of patients during the year they were deliberately boarded in a separate section in the emergency department was significantly higher than in other years, when such policy did not take place. A direct link was demonstrated between LOS in the emergency department and mortality. LOS of patients who died was significantly higher than that of patients who did not die. CONCLUSIONS: Boarding patients in the emergency department increases mortality and LOS. Ways to minimize the phenomena should be explored. DISCUSSION: For the first time, the effects of boarding patients in the emergency department in Israel are studied. The issue of boarding patients in emergency departments should be a central issue addressed by Israel's health system. PMID- 26821501 TI - [SYNCOPE CAUSED BY INTRA-OCULAR TIMOLOL]. AB - INTRODUCTION: Timolol eye-drops are commonly used for the treatment of glaucoma. Despite being topically applied, some systemic absorption occurs with the resulting adverse reactions related to its beta-adrenoreceptor blocking activity CASE PRESENTATION: We report the case of a 68 years old healthy male who was admitted to our department for further workup following two episodes of syncope. Medical history taking revealed that the episodes of syncope occurred soon after beginning treatment with intra-ocular timolol for glaucoma. An electrocardiogram demonstrated a sinus bradycardia rhythm and a prolonged PR interval, consistent with the negative effects of a beta adrenergic receptor antagonist on the heart's electrical generation and conduction system. DISCUSSION: This case demonstrates the potential for dangerous systemic side effects of a topically-applied medication. It also highlights the importance of thorough medical history taking in the evaluation of syncope, including inquiry regarding the use of all, especially new, medications. CONCLUSION: Detailed medical history taking can help in avoiding the performance of an expensive and unnecessary workup. PMID- 26821502 TI - [THE DIFFERENT PRESENTATIONS OF PERIOCULAR MOLLUSCUM CONTAGIOSUM]. AB - INTRODUCTION: Periocular molluscum contagiosum nodules typically appear in a classical presentation. However, the presentation can be different. This makes the diagnosis and the decision on treatment difficult. AIM: To report different clinical presentations of periocular molluscum contagiosum and to examine their epidemiological, clinical and histopathological features. METHODS: For all patients who were diagnosed with periocular molluscum contagiosum during the years 1995-2014, the following data was extracted from the patients' files: gender, age at the time of diagnosis, location of the lesion, number and dimensions of lesions, clinical presentation, histopathological features, suspected clinical diagnosis before histopathological diagnosis and treatment. A classification according to different presentations was suggested and the epidemiological, clinical and histopathological features of each presentation were examined. RESULTS: Molluscum contagiosum was diagnosed in 30 patients: 10 males (33.33%) and 20 females (66.66%). The mean age of diagnosis was 19.3 years old, one patient was immunosuppressive and 29 patients were immunocompetent. Six different clinical presentations were seen: Typical, umbilicated dome shaped lesion (19 cases), big lesion (4 cases), conglomerated lesions (4 cases), erythematous lesion (1 case), inflamed lesion (1 case), and pedunculated lesion (1 case). In all cases the diagnosis was confirmed by histopathological examination and the treatment was surgical excision. CONCLUSION: According to this case series of periocular molluscum contagiosum, which is one of the largest published thus far in the ophthalmic literature, six distinct different clinical presentations are suggested. These lesions should be suspected not just in children and in immunosuppressive adult patients but also in immunocompetent patients of all ages. PMID- 26821503 TI - [BISPHENOL A--AN INFAMOUS MOLECULE]. AB - Bisphenol A (BPA) is a monomer found in plastic products used daily for the storage and consumption of food and beverages, such as plastic bottles, containers, and even toys. The molecule leaches out into the food, increasingly if exposed to warm temperatures and high acidity. BPA is known for many negative effects on the human body; for instance it acts as an xenoestrogen and influences fertility and gestation and might also have carcinogenic effects, causing breast and prostate cancer. Although it has not yet been proven as a direct cause of autoimmunity, many of the effects of BPA can be related to the pathogenesis of autoimmune disease (AID). Its estrogenic behavior modulates the immune system, it encourages the secretion of Prolactin that is known to be associated to AID, it creates oxidative stress that triggers the immune system and so on. Therefore there is room to advise individuals at risk for AID to avoid the consumption of BPA, similar to guidelines for pregnant women. PMID- 26821504 TI - [COMPLICATIONS RELATED TO PATIENT POSITIONING: KEY POINTS IN PREVENTION AND MANAGEMENT]. AB - Patient positioning during surgery can have profound short and long term implications for the patient. Each position carries some degree of risk to the patient, which is magnified in prolonged operations, surgeries performed under general anesthesia and when position manipulations are required in order to gain best surgical access. Prevention is the mainstay of the management of positioning. Therefore, it is crucial that all operating room personnel will be familiar with the different surgical positions and their general and specific position-related injury potential. It is also important that these complications are diagnosed promptly and managed appropriately in the post-operative period. The purpose of the following review is to summarize the positioning-related complications, in particular peripheral nerve injuries, and emphasize correct positioning recommendations and preventive measures. PMID- 26821505 TI - [INTERLEUKIN 1 INHIBITORS--A NEW HORIZON IN THE TREATMENT OF FAMILIAL MEDITERRANEAN FEVER]. AB - Familial Mediterranean Fever (FMF) is a common genetic auto-inflammatory disease in the Middle Eastern population. Colchicine is the only proven treatment for the prevention of FMF attacks and reactive amyloidosis. However, 5-10% of FMF patients do not respond to colchicine, and an additional 5% are intolerant to it. Progress in the understanding of FMF and the recognition of the central role of IL-1 in its pathophysiology has led to the introduction of IL-1 inhibitors in FMF patients who are unresponsive to colchicine. In this paperwe review the clinical experience gained with IL-1 inhibitors in FMF. Overall, it appears that IL-1 inhibitors are safe and may serve as an alternative in FMF patients resistant to colchicine. PMID- 26821506 TI - [THE APPROACH TO NAUSEA AND VOMITING IN PREGNANCY]. AB - Nausea and vomiting of pregnancy (NVP) is the most prevalent medical condition during gestation. Approximately 85% of pregnant women suffer from some degree of this condition, while hyperemesis gravidarum (HG), the most severe form, affects up to 2% of women. Although being the leading cause for hospitalization during pregnancy, NVP has received little attention from the medical community. NVP negatively affects women's quality of life, household activity and work productivity. In Canada, the financial cost of NVP, ranges from $132 to $653 per woman/week. In extreme cases, severe NVP results in therapeutic abortions. On the other hand, NVP has been shown to have a protective effect against spontaneous abortions and congenital malformations. Lately, there has been an interest in the hypothesis that NVP is a mechanism protecting the fetus from phytochemicals. Early treatment can prevent future complications and deterioration of the symptoms. Various studies have demonstrated the effectiveness and safety of antiemetic therapy in pregnancy. However, fear of teratogenicity and lack of clinical guidelines lead to trial and error NVP management. We present an updated algorithm for the management of NVP. PMID- 26821507 TI - [HIGH ALTITUDE EXPOSURE IN TRAVELERS WITH PREEXISTING MEDICAL CONDITIONS]. AB - The number of travelers visiting high altitude regions is increasing. High altitude areas have become more accessible in recent years, and reaching areas at altitudes over 3000 meters above sea level has become more common than before. In many circumstances older travelers, who are more likely to have pre-existing chronic diseases and for whom altitude and hypoxic condition might be a risk, reach high altitudes in a fast and tight schedule, therefore having a shorter time for adaptation and acclimatization. Pre-travel consultation, including the discussion of chronic illnesses and medication use, is therefore crucial for the reduction of the risk of acute mountain sickness and preventing the deterioration of their pre-existing medical conditions. PMID- 26821508 TI - [DR. SHOSHANA SZKOP-FRENKIEL: THE FIRST FEMALE PLASTIC SURGEON IN ISRAEL]. AB - In the history of Israeli medicine, Dr. Shoshana Szkop-Frenkiel is regarded as the first plastic surgeon in the country and among the founders of the profession of plastic surgery. This article describes the long road she traveled, from her acceptance into medical studies in Vilna--at a time when the entry of any woman to the faculty of medicine was strictly limited and of Jewish women in particular; her emigration to Eretz Israel and her struggles as she underwent training in internal medicine at the "Hadassah" Hospital in Tel-Aviv, when she was denied training as a surgeon; and up to the moment she was accepted by the plastic surgery unit of the Tel Hashomer Hospital and became the first such female practitioner in Israel. Dr. Shoshana Szkop-Frenkiel thus fulfilled a childhood dream to become a surgeon at a time when women were excluded from surgery on the grounds that it called for "male" characteristics. This article is intended to illustrate the character of a female doctor pursuing a career in surgery during the time of the British Mandate, to illuminate her professional travails in Israel, and to emphasize her important contribution in the field. PMID- 26821509 TI - [A patient's decision to be released: the medical dilemma in the department of emergency medicine]. PMID- 26821510 TI - [MENTALIZING DEFICIT IN NEUROLOGICAL DISORDERS: A REVIEW ARTICLE]. AB - INTRODUCTION: Mentalization is the ability to attribute mental states (intentions, desires, thoughts, emotions) to others, and hence to predict their behaviour. This ability fundamentally determines our participation in social relationships and adaptation to society. A significant proportion of the disorders of the central nervous system (CNS) affects those brain structures and neurotransmitter systems that play a role in the mentalizing processes. Accordingly, a number of CNS disorders may be associated with mentalizing deficits, which may affect the outcome of these diseases. Here, we review recent research on mentalizing abilities in neurological diseases. METHODS: An internet database search was performed to identify publications on the subject. RESULTS: Sixty-two publications in English corresponded to the search criteria. These publications reported impaired mentalization in several neurological disorders (e.g. epilepsy, Parkinson's disease, multiple sclerosis, dementias, traumatic brain injury). DISCUSSION: The results indicate that a number of neurological disorders associate with mentalizing deficit. This deficit is often present in the early stages of the diseases and has a prognostic value, which in turn emphasizes the importance of the early detection and adequate rehabilitation. PMID- 26821511 TI - [SLEEP DISORDERED BREATHING AND EPILEPSY: RELATIONSHIPS AND THERAPEUTIC CONSIDERATIONS]. AB - The importance of the sleep related breathing disorders (obstructive sleep apnea syndrome, central sleep apnea, and Cheyne-Stokes breathing) in the pathophysiology crebro- and cardiovascular disorders is well known. The relationship of sleep related breathing abnormalities and epilepsy is also important but underestimated in the daily practice. The relation is bidirectional. The breathing abnormalities in sleep may play important role in generating epileptic seizure, but the adverse effect of seizure and antiepileptic therapy (generation of apneas and hypopneas) may worsen the seizure control. The effect of new therapies (vagal nerve and deep brain stimulation) on the sleep architecture and sleep disordered breathing must be examined and discussed. Here we present a brief case of epileptic patient with deep brain stimulation therapy on sleep as well. The examination of the sleep related breathing abnormalities in epilepsy patient may help improve the effectiveness of antiepileptic therapy. PMID- 26821512 TI - [EARLIER AND MORE EFFICIENTLY: THE ROLE OF DEEP BRAIN STIMULATION IN PARKINSON'S DISEASE: PRESERVING THE WORKING CAPABILITY]. AB - BACKGROUND: The recently published "EarlyStim" study demonstrated that deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD) with early fluctuations is superior to the optimal pharmacological treatment in improving the quality of life and motor symptoms, and preserving sociocultural position. Our retrospective investigation aimed to evaluate if DBS therapy was able to preserve the working capabilities of our patients. METHODS: We reviewed the data of 39 young (< 60 years-old) PD patients who underwent subthalamic DBS implantation at University of Pecs and had at least two years follow-up. Patients were categorized into two groups based on their working capabilities: Patients with active job ("Job+" group, n = 15) and retired patients (without active job, "Job-" group, n = 24). Severity of motor symptoms (UPDRS part 3), quality of life (EQ-5D) and presence of active job were evaluated one and two years after the operation. RESULTS: As far as the severity of motor symptoms were concerned, similar (approximately 50%) improvement was achieved in both groups. However, the postoperative quality of life was significantly better in the Job+ group. Majority (12/15, 80%) of Job+ group members were able to preserve their job two years after the operation. However, only a minimal portion (1/24, 4.2%) of the Job- group members was able to return to the world of active employees (p < 0.01, McNemar test). CONCLUSION: Although our retrospective study has several limitations, our results fit well with the conclusions of "EarlyStim" study. Both of them suggest that with optimal timing of DBS implantation we may preserve the working capabilities of our patients. PMID- 26821513 TI - [NOVEL STRATEGY IN THE RADIOTHERAPY OF METASTATIC BRAIN TUMORS: SIMULTANEOUS WHOLE BRAIN RADIOTHERAPY AND INTEGRATED STEREOTACTIC RADIOSURGERY]. AB - BACKGROUND AND PURPOSE: Treatment of central nervous system (CNS) tumors has always played an important role in development of radiotherapy techniques. Precise patient immobilisation, non-coplanar field arrangement, conformal treatment, arc therapy, radiosurgery, application of image fusion to radiation planning or re-irradiation were first introduced into clinical routine in the treatment of brain tumors. METHODS: A modern multifunctional radiation instrument, Novalis TX has been installed at the University of Pecs two years ago. New methods, such as real time 3D image guided therapy, dynamic arc therapy and ultra-conformity offer further progress in treatment of CNS tumors. Whole brain irradiation and simultaneous fractionated stereotactic radiosurgery or integrated boost seem to be an optimal method in the treatment of not only soliter or oligo, but even a higher number (4-9) and not typically radiosensitive brain metastases. The new treatment strategy is illustrated by presentation of four case histories. RESULTS: Treatment protocol was completed in all cases. Treatment period of 1.5 to 3 weeks, and treatment time of only a few minutes were not stressful for the patients. A quite remarkable clinical improvement as to general condition of the patients was experienced in three cases. Follow-up images confirmed either remission or a stable disease. CONCLUSIONS: Simultaneous whole brain radiotherapy and integrated stereotactic radiosurgery is a reproducible, safe method that offers an effective irradiation with delivery of definitive dosage even in cases with radio-insensitive brain metastasis. PMID- 26821514 TI - [HEALTH INSURANCE ASPECTS OF PHYSIOTHERAPEUTIC CARE OF NEUROLOGY DISORDERS IN OUTPATIENT CARE]. AB - BACKGROUND AND PURPOSE: The aim of our study is to analyse the ambulatory rehabilitation care of patients with neurological disorders in the field of physiotherapy. METHODS: Data derive from the database of the Hungarian National Health Insurance Fund Administration (year 2009). The analyses covered patients with diagnosis "G00-G99 Diseases of the nervous system" according to the International Classification of Diseases and underwent physiotherapy treatment. RESULTS: In 2009 altogether 190986 patients with neurological disorders received physiotherapy treatment in outpatient care, representing 1331675 cases and got 388.215 million Hungarian Forint health insurance reimbursement. The number of patients with nerve, nerve root and plexus disorders was 39 patients/10 000 population for males and 66 patients/10000 population for females. The number of patients with cerebral palsy and other paralytic syndromes was 49 patients/10000 population for males and 35 patients/10000 population for females. The number of patients with episodic and paroxysmal disorders was 33 patients/10000 population for males and 52 patients/10000 population for females. CONCLUSION: In the outpatient physiotherapy care the utilization indicators for female patients were higher in nerve, nerve root and plexus disorders and episodic and paroxysmal disorders, while in cerebral palsy and other paralytic syndromes the utilization by male patients was higher. There are important age and gender inequalities in the utilization of physiotherapy care of patients with neurological disorders. PMID- 26821515 TI - ATTACHMENT AS A PREDICTOR OF RISK FOR EATING DISORDERS ON A REPRESENTATIVE HUNGARIAN ADULT SAMPLE. AB - BACKGROUND AND PURPOSE: Many studies confirm the relationship between attachment disturbances and (the severity of) eating disorders, however among them only one Hungarian study can be found. The exact predisposing traits of attachment and the strength of relationship is still uncleared. Our aim was to explore these aspects. METHODS: Study was based on a cross-sectional nationally representative survey, called "Hungarostudy 2013" (N = 2000, 46.9% males, mean age 46.9 years, SD = 18.24 years). Measures: Sociodemographic and self-reported anthropometric data (weight and height), short Hungarian version of Relationship Scale Questionnaire, SCOFF questionnaire and short Hungarian version of Beck Depression Inventory. RESULTS: The frequency of risk for eating disorders (anorexia or bulimia nervosa) was 3.9% (N = 76) among the respondents (N = 1860). Attachment anxiety was significantly higher in the risk for eating disorders group (t (1888) = -3.939, p < 0.001), and significantly predicted the risk or eating disorders after adjusting for the potential background variables (OR = 1.09, p = 0.040). Detachment was not a significant predictor of risk for eating disorders (OR = 0.98, p = 0.515). Younger age (OR = 0.97, p < 0.001), higher level of depression (OR = 1.09, p < 0.001) and higher body mass index (OR = 1.08, p < 0.001) were also significant cross-sectional predictors of risk for eating disorders. The explained variance of the model was 10.7%. CONCLUSION: The study supported, that higher attachment anxiety is associated with the increased risk of eating disorders, with a possible therapeutic relevance. Assessment of attachment's further aspects and creating multivariable models are required for more thorough understanding and optimising of intervention points. PMID- 26821516 TI - HYPERGLYCAEMIC HEMIBALLISMUS: IMPLICATIONS FROM CONNECTIVITY ANALYSIS FOR COGNITIVE IMPAIRMENTS. AB - Hyperglycaemia induced movement disorders, such as hemiballism are rare disorders. The syndrome is characterised by the triad of hemiballism, contralateral T1-hyperintense striatal lesion and non-ketotic hyperglycaemia. Here we report a patient with untreated diabetes presenting with acute onset of hemiballism. MRI revealed T1 hyperintensity of the head of the caudate nucleus and the anterior putamen. The patient also had acantocytosis. Based on the detailed examination of the neuroradiological results and earlier findings we will discuss the pathomechanism. Based on previous findings microhemorrhages, extensive mineralisation, gemistocytic astrocytosis might play a role in the development of the imaging signs. The connectivity pattern of the striatal lesion showed extensive connections to the frontal cortex. In coexistence with that the most severe impairment was found on the phonemic verbal fluency task measuring frontal executive functions. PMID- 26821517 TI - THE DIAGNOSTIC AND MANAGEMENT CHALLENGES FOR POSTERIOR REVERSIBLE LEUCOENCEPHALOPATHY SYNDROME. AB - Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity characterized by epileptic seizures, headaches, altered mental status and focal neurological signs. Hypertension is the second most common condition associated with PRES. The 50-year-old-male patient with, right-sided hemiparesis and speech disturbances admitted to our clinic. His blood pressure at the emergency service was 220/140 mmHg. A left putaminal hematoma was seen in his CT and MRI. In his brain MRI, FLAIR and T2 -weighted sequences showed bilateral symmetric diffuse hyperintensities in the brain stem, basal ganglia, and occipital, parietal, frontal, and temporal lobes. After the intense antihypertensive drug treatment, his blood pressure came to normal limits within a week. During his hospitalisation he had a recurrent speech disturbance lasting an hour. His electroencephalography was normal. In his repeated diffusion weighted MRI, an acute lacunary infarct was seen on right centrum semiovale. Two months later, the control MRI showed only the previous lacuner infarcts and the chronic putaminal hematoma. We presented a case developping either a cerebral hemorrhage or a lacunar infarction due to PRES. The main reason of the following complications of the disease was delayed diagnosis. Uncontrolled hypertension was guilted for the events. PMID- 26821518 TI - A RARE COMPLICATION OF A RARE DISEASE; STROKE DUE TO RELAPSING POLYCHONDRITIS. AB - Relapsing polychondritis (RP) is an episodic and progressive inflammatory disease of cartilaginous structures. Its diagnosis is based primarily on clinical features such as laboratory parameters, biopsy. Neurological complications occur in 3% of the cases and are classified as an important cause of death. The cranial nerve disorders are most common but hemiplegia, ataxia, myelitis, polyneuritis, seizures, confusion, hallucination and headache can also happen. The aetiology of central nervous system involvement is still unknown. Moreover stroke has rarely reported in these patients. The diagnosis of stroke is challenging because of its rarity among these patients. Perhaps vasculitis is the common underlying mechanism. Also meningitis and encephalitis can occur during the course of RP. A 44 year-old woman was admitted with uncontemplated left hemiparesis, redness, swelling, and tenderness of the metacarpophalangeal and interphalangeal joints of the right hand and the cartilaginous portion. White blood cell count, C-reactive protein and the erythrocyte sedimentation rate were elevated. Vasculitis biomarkers were normal in our patient. Carotid and vertebral artery doppler ultrasonography, cranial and cervical MR Angiography were normal. Echocardiography showed a mild mitral valve prolapse and regurgitation. Our patient had the history of auricular polychondritis but she had not been diagnosed. Hemiparesis was her first neurological manifestation that led her to doctors for diagnosis. Our patient fulfilled the criteria of RP so no biopsy was needed. She was treated with oral prednisolone (80 mg/day) and aspirin (300 mg/day) and now she is on 10 mg prednisolone and 150 mg azathioprine. Two months later her physical and neurological symptoms returned to normal. PMID- 26821519 TI - [Analysis of Cases with Elevated Blood (1->3)-beta-D-glucan in Relation to an Infection Marker, Neutrophil CD64 Expression]. AB - (1->3)-beta-D-glucan (BDG) is a constituent of the fungal cell wall and its blood level is known as a marker of fungal infection including pneumocystis pneumonia (PCP). Meanwhile, peripheral blood neutrophil CD64 expression (CD64) is upregulated in various infections. We analyzed patients with positive BDG (cut off 11.0 pg/mL) and those whose CD64 was measured simultaneously. In patients who visited our hospital from 2005 to 2011, BDG was measured in 3,960 samples. The number of positive samples were 441 obtained from 185 patients. In patients with positive BDG, the initial BDG was 24.3 [16.4-70.5] pg/mL (median [interquartile range]). Positive BDG samples were derived mainly from the department of Rheumatology or that of Allergy and Respirology. Common primary diseases were rheumatoid arthritis (RA) or other connective tissue diseases, followed by malignancy, none (only abnormal chest X-ray) and bronchial asthma. The rates of afebrile patients, patients on immunosuppressive therapy and those with a normal range of white blood cell count were 63.7%, 50.9% and 40.8%, respectively. The main causes of positive BDG were PCP (n = 38, 20.5%) and non-PCP mycosis (n = 48, 25.9%, including 26 cases of aspergillosis). Others (99 patients, 53.6%) had positive BDG of unknown origin and 53 of them ameliorated spontaneously, most of whom could have been examples of pseudo-positive BDG. The number of deceased patients was 57 (30.8%) consisting of 9 PCP, 16 non-PCP mycosis and others. The median initial positive BDG levels in patients with PCP, non-PCP mycosis and others were 49.9, 28.9 and 19.7pg/mL, respectively. The positive rate of CD64 (cut off 2,000 molecules/cell) measured simultaneously with initial positive BDG was 77.8%. In RA patients with PCP, 94.7% of them had positive CD64 and the levels of CD64 were significantly higher than those in RA patients with bacterial pneumonia (median 9,386 vs 4,399 molecules/cell) in that same period. The positive rate of CD64 was lower in patients with positive BDG of unknown origin than those with PCP or non-PCP mycosis, which implies positive CD64 can exclude pseudo-positive BDG. Immunosuppressed patients often exhibit positive BDG. Simultaneous measurement of BDG and CD64, a quick pan-infection marker, assists the decision whether the positive BDG is true or false-positive. PMID- 26821520 TI - [Infectivity Titers of Each Component of the Influenza Virus in the Live Vaccine Purchased from a Parallel Import Distributing System]. AB - Currently in Japan, the only approved influenza vaccine is the inactivated vaccine which is injected subcutaneously. On the other hand, there is a live vaccine available elsewhere in the world. Flumist, an intranasal influenza live vaccine which contains four strains of infectious viruses, has been used in the United States for more than 10 years; the vaccine has been found effective in clinical trials, while it has some limitations such as those on subjects for the administration, strict storage conditions, relatively short expiration date etc. It is not yet approved in Japan, but available through personal import by some medical institutions, and prescribed based on the decision of the doctor. However, in Japan, there is no checking system whether the vaccine contains appropriate amounts of infectious viruses or not. In the present study, we purchased 2013-14 and 2014-15 years' lots of Flumist from a parallel importer and measured the amount of infectious viruses of each component of them using the focus assay. Consequently, for type A influenza viruses, the titers of both of H1N1pdm09 and H3N2 viruses in the 2013-14's lot were 1/30 of the lower limit of those shown in the package insert and 1/10 in 2014-15's lot, while those of type B viruses, both of B/Massachusetts and B/Brisbane viruses marginally cleared the lower limit. The digital PCR analysis showed that the absolute genome copy numbers of type A viruses were 1/10 of those of type B viruses. The relatively higher titer of B/Massachusetts also gradually decreased over time during its storage at 4 degrees C and finally reached the lower limit at about one week before the expiration date. In case it is approved officially in the future to be used in Japan, some studies will be required to elucidate the minimum viral titers of the components necessary for effective live vaccine. In addition, there should be a system to check the titer during the distribution process in Japan. PMID- 26821521 TI - [Invasive Infections Caused by Nontyphoidal Salmonella sp. in Childhood Clinical Features and Incidence Trends between 1994 and 2014]. AB - Little is known about the clinical characteristics of invasive infections caused by nontyphoidal Salmonella sp. in childhood and the temporal changes of their incidence over a long period of time. In order to clarify these issues, we retrospectively analyzed the records of 17 such infected children admitted between August 1994 and December 2014 to our center. We divided the study period into the first (1994-1999), second (2000-2004), third (2005-2009), and fourth (2010-2014) periods. The ages of the 17 patients ranged from 2 days to 13 years. Clinical syndrome included bacteremia with enteritis (n = 13), followed by bacteremia or sepsis alone, (n = 2), osteomyelitis (n = 1), and meningitis (n = 1). The affected patient numbers in the first to fourth periods were 10, 5, 2, and 0, respectively, and the decreasing trend was significant (trend p < 0.001). This significant trend held up even after correction by the number of in-patients during each quarter period (trend p = 0.009). In the 14 cases of bacteremia with or without enteritis, excluding two neonatal cases and one case of osteomyelitis, most patients (n = 13, 93%) had WBC of <15,000/uL with a wide range of serum CRP levels (0.8-20.4mg/dL) on admission. Thus, it was very difficult to diagnose these bacteremia cases based on blood tests alone, and we needed to consider such risk factors of bacteremia as high fever, poor general condition, and younger age. O group serotypes of the isolates were as follows: O9 (n = 11), O7 (n = 5), and O4 (n = 1). Of the 15 strains evaluated, two strains were resistant to ampicillin and one each was resistant and intermediately resistant to fosfomycin. All strains were susceptible to cefotaxime, ofloxacin or levofloxacin, and trimethoprim-sulfamethoxazole. We were also presented with two rare cases : one involved sepsis due to vertical transmission and the other involved meningitis. The latter case had clinical relevance in that recurrence developed 3 weeks after treatment with susceptible antibiotics. In conclusion, this study is the first report on invasive infections caused by nontyphoidal Salmonella sp. in childhood in Japan, and provides important information on their clinical features and incidence trends over the last 20 years. PMID- 26821522 TI - [Performance Assessment of a Newly Developed Rapid Diagnostic Reagent for Human Immunodeficiency Virus]. AB - Extremely early diagnosis of human immunodeficiency virus (HIV) infection has been considered highly important for its treatment. We conducted a performance assessment of a newly developed rapid diagnostic reagent for HIV by using a fourth-generation immunochromatographic assay (Alere HIV Combo). We used whole blood, plasma, and serum samples obtained from 250 Japanese adults who visited the Kawasaki Medical School Hospital and underwent HIV screening tests. We also used 12 types of commercial HIV-1 sero- conversion panels and World Health Organization standard antigens. This method, which has a detection sensitivity of 100% and a specificity of 99.3%, was as accurate as the chemiluminescent immunoassay (CLIA) method. In a sensitivity test using seroconversion panels in the early phase of infection, the mean duration until positive conversion was 19.3 days. With this method having a high detection sensitivity for HIV-1p24 antigen, the results from whole-blood samples were the same as those from plasma and serum samples. Therefore, it can be considered as a useful rapid measurement method for general practice. PMID- 26821523 TI - [Streptococcal Toxic Shock-like Syndrome due to Streptococcus suis Serotype 2 in a Japanese Pig Farmer]. AB - Streptococcus suis is a major swine pathogen. It has recently been recognized as an emerging zoonosis that causes mainly meningitis and sepsis in human. In particular, toxic shock-like syndrome (TSLS) caused by this pathogen has a high mortality rate. However, misidentification of S. suis by conventional biochemical and commercial identification tests is not rare. The patient was a 71-year-old man who worked as a pig farmer who was admitted for fever, oliguria and subcutaneous hemorrhage. He was diagnosed as having septic shock and blood culture was positive for Gram-positive cocci, mainly diplococcus. This pathogen was identified with S. suis with using MALDI-TOF MS analysis, though a commercial Gram-Positive bacteria identification kit revealed viridans streptococci. His clinical features met the diagnostic criteria of TSLS, and ceftriaxone and clindamycin were administered. On admission day 28, he was discharged in good condition. PMID- 26821524 TI - [The Value of Infectious Diseases Specialists in the Outpatient Setting at a Comprehensive Cancer Center in Japan: What do Oncology Specialists Request?]. PMID- 26821525 TI - [The Influenza Outbreak in 2014/2015 Season, in Sumida Ward, through the (Nursery) School Absenteeism Surveillance System]. PMID- 26821526 TI - A Closure Study of the Reaction between Sulfur Dioxide and the Sulfate Radical Ion from First-Principles Molecular Dynamics Simulations. AB - In a previous study, we applied quantum chemical methods to study the reaction between sulfur dioxide (SO2) and the sulfate radical ion (SO4(-)) at atmospheric relevant conditions and found that the most likely reaction product is SO3SO3(-). In the current study, we investigate the chemical fate of SO3SO3(-) by reaction with ozone (O3) using first-principles molecular dynamics collision simulations. This method assesses both dynamic and steric effects in the reactions and therefore provides the most likely reaction pathways. We find that the majority of the collisions between SO3SO3(-) and O3 are nonsticking and that the most frequent reactive collisions regenerate sulfate radical ions and produce sulfur trioxide (SO3) while ejecting an oxygen molecule (O2). The rate of this reaction is determined to be 2.5 * 10(-10) cm(3) s(-1). We then conclude that SO4(-) is a highly efficient catalyst in the oxidation of SO2 by O3 to SO3. PMID- 26821528 TI - Hypertension in young adults. AB - Hypertension remains a major societal problem affecting 76 million, or approximately one third, of US adults. While more prevalent in the older population, an increasing incidence in the younger population, including athletes, is being observed. Active individuals, like the young and athletes, are viewed as free of diseases such as hypertension. However, the increased prevalence of traditional risk factors in the young, including obesity, diabetes mellitus, and renal disease, increase the risk of developing hypertension in younger adults. Psychosocial factors may also be contributing factors to the increasing incidence of hypertension in the younger population. Increased left ventricular wall thickness and mass are increasingly found in young adults on routine echocardiograms and predict future cardiovascular events. This increasing incidence of hypertension in the young calls for early surveillance and prompt treatment to prevent future cardiac events. In this review we present the current epidemiological data, potential mechanisms, clinical implications, and treatment of hypertension in young patients and athletes. PMID- 26821527 TI - An analysis toolbox to explore mesenchymal migration heterogeneity reveals adaptive switching between distinct modes. AB - Mesenchymal (lamellipodial) migration is heterogeneous, although whether this reflects progressive variability or discrete, 'switchable' migration modalities, remains unclear. We present an analytical toolbox, based on quantitative single cell imaging data, to interrogate this heterogeneity. Integrating supervised behavioral classification with multivariate analyses of cell motion, membrane dynamics, cell-matrix adhesion status and F-actin organization, this toolbox here enables the detection and characterization of two quantitatively distinct mesenchymal migration modes, termed 'Continuous' and 'Discontinuous'. Quantitative mode comparisons reveal differences in cell motion, spatiotemporal coordination of membrane protrusion/retraction, and how cells within each mode reorganize with changed cell speed. These modes thus represent distinctive migratory strategies. Additional analyses illuminate the macromolecular- and cellular-scale effects of molecular targeting (fibronectin, talin, ROCK), including 'adaptive switching' between Continuous (favored at high adhesion/full contraction) and Discontinuous (low adhesion/inhibited contraction) modes. Overall, this analytical toolbox now facilitates the exploration of both spontaneous and adaptive heterogeneity in mesenchymal migration. PMID- 26821529 TI - Robotic Prostatectomy on the Web: A Cross-Sectional Qualitative Assessment. AB - BACKGROUND: Many patients diagnosed with prostate cancer search for information on robotic prostatectomy (RobP) on the Web. We aimed to evaluate the qualitative characteristics of the mostly frequented Web sites on RobP with a particular emphasis on provider-dependent issues. MATERIALS AND METHODS: Google was searched for the term "robotic prostatectomy" in Europe and North America. The mostly frequented Web sites were selected and classified as physician-provided and publically-provided. Quality was measured using Journal of the American Medical Association (JAMA) benchmark criteria, DISCERN score, and addressing of Trifecta surgical outcomes. Popularity was analyzed using Google PageRank and Alexa tool. Accessibility, usability, and reliability were investigated using the LIDA tool and readability was assessed using readability indices. RESULTS: Twenty-eight Web sites were physician-provided and 15 publically-provided. For all Web sites, 88% of JAMA benchmark criteria were fulfilled, DISCERN quality score was high, and 81% of Trifecta outcome measurements were addressed. Popularity was average according to Google PageRank (mean 2.9 +/- 1.5) and Alexa Traffic Rank (median, 49,109; minimum, 7; maximum, 8,582,295). Accessibility (85 +/- 7%), usability (92 +/- 3%), and reliability scores (88 +/- 8%) were moderate to high. Automated Readability Index was 7.2 +/- 2.1 and Flesch-Kincaid Grade Level was 9 +/- 2, rating the Web sites as difficult to read. Physician-provided Web sites had higher quality scores and lower readability compared with publically-provided Web sites. CONCLUSION: Websites providing information on RobP obtained medium to high ratings in all domains of quality in the current assessment. In contrast, readability needs to be significantly improved so that this content can become available for the populace. PMID- 26821530 TI - Combined Angiogenesis and Proliferation Markers' Expressions as Long-Term Prognostic Factors in Renal Cell Cancer. AB - OBJECTIVES: The aim of this study was to evaluate the expression of MIB-1, BCL-2, VEGFR3, and CD31 and their associations with long-term survival in patients with renal cell cancer (RCC). PATIENTS AND METHODS: This study consisted of 224 RCC patients who underwent radical nephrectomy from 1985 to 1995. Follow-up continued for up to over 20 years. MIB-1 and BCL-2 expression were analyzed alone, and additionally, the expression of MIB-1, BCL-2, VEGFR3, and CD31 were combined in pairs using the following groups: low/low, low/high, high/low, and high/high. RESULTS: Low BCL-2 expression (hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.42-3.31; P < .001 compared with high BCL-2 in univariate analysis) and high MIB-1 expression (HR, 2.05; 95% CI, 1.32-3.19; P = .001 in multivariate analysis) were found to associate for poorer survival in RCC. In multivariate analysis, the combination of high MIB-1/low BCL-2 was associated with poor survival compared with low MIB-1/high BCL-2 (HR, 3.20; 95% CI, 1.66-6.17; P = .001), and the combination of low VEGFR3/high CD31 was associated with poor survival (HR, 2.48; 95% CI, 1.29-4.78; P = .007) compared with high VEGFR3/high CD31. CONCLUSIONS: Compared with high BCL-2 expression in combination with low or high MIB-1, VEGFR3, or CD31 expression, low BCL-2 expression in combination with low or high MIB-1, VEGFR3, or CD31 expression has poorer survival in the long term follow-up of patients with RCC. Analysis of MIB-1, BCL-2, VEGFR3, and CD31 expression might be a useful additional marker to tailor the follow-up of RCC patients. PMID- 26821531 TI - Methods for the integration of multi-omics data: mathematical aspects. AB - BACKGROUND: Methods for the integrative analysis of multi-omics data are required to draw a more complete and accurate picture of the dynamics of molecular systems. The complexity of biological systems, the technological limits, the large number of biological variables and the relatively low number of biological samples make the analysis of multi-omics datasets a non-trivial problem. RESULTS AND CONCLUSIONS: We review the most advanced strategies for integrating multi omics datasets, focusing on mathematical and methodological aspects. PMID- 26821532 TI - The risk of malaria in Ghanaian infants born to women managed in pregnancy with intermittent screening and treatment for malaria or intermittent preventive treatment with sulfadoxine/pyrimethamine. AB - BACKGROUND: Several studies have reported an association between malaria infection of the placenta and the risk of malaria in young children in the first year of life, but it is not known if this is causal, or influenced by malaria control measures during pregnancy. This paper compares the incidence of malaria in infants born to mothers who received either intermittent preventive treatment with sulfadoxine/pyrimethamine (IPTp-SP) or screening with a rapid diagnostic test and treatment with artemether-lumefantrine (ISTp-AL) during their pregnancy. METHODS: From July 2011 to April 2013, 988 infants of women enrolled in a trial of IPTp-SP versus ISTp-AL in the Kassena-Nankana districts of northern Ghana were followed to determine the risk of clinical malaria during early life, and their risk of parasitaemia and anaemia at 6 and 12 months of age. In addition, the incidence of clinical malaria in infants whose mothers had malaria infection of the placenta was compared with that in infants born to women free of placental malaria. RESULTS: The incidence of clinical malaria was 0.237 and 0.211 episodes per child year in infants whose mothers had received ISTp-AL or IPTp-SP, respectively. The adjusted incidence rate ratio and the adjusted rate difference were 0.94 (95% CI 0.68, 1.33) and 0.029 (95% CI -0.053, 0.110) cases per child year at risk respectively. The incidence of clinical malaria was similar in infants born to women with placental malaria (0.195 episodes per child year) and in infants of women without placental malaria (0.224 episodes per child year) (rate ratio = 0.86 [95% CI 0.54, 1.37]). CONCLUSION: Infants born to women managed with ISTp-AL during pregnancy were not at greatly increased risk of malaria compared with infants born to women who had received IPTp-SP. The incidence of malaria in infants was similar whether or not their mother had had placental malaria. PMID- 26821533 TI - Work-family balance by women GP specialist trainees in Slovenia: a qualitative study. AB - BACKGROUND: Women physicians face many challenges while balancing their many roles: doctor, specialist trainee, mother and partner. The most opportune biological time for a woman to start a family coincides with a great deal of demands and requirements at work. In this study we explored the options and capabilities of women GP specialist trainees in coordinating their family and career. METHODS: This is a phenomenological qualitative research. Ten GP specialist trainees from urban and rural areas were chosen by the purposive sampling technique, and semi-structured in-depth interviews were conducted, recorded, transcribed and analysed by using thematic analysis process. Open coding and the book of codes were formed. Finally, we performed the process of code reduction by identifying the themes, which were compared, interpreted and organised in the highest analytical units--categories. RESULTS: One hundred fifty five codes were identified in the analysis, which were grouped together into eleven themes. The identified themes are: types, causes and consequences of burdens, work as pleasure and positive attitude toward self, priorities, planning and help, and understanding of superiors, disburdening and changing in specialisation. The themes were grouped into four large categories: burdens, empowerment, coordination and needs for improvement. CONCLUSION: Women specialist trainees encounter intense burdens at work and home due to numerous demands and requirements during their specialisation training. In addition, there is also the issue of the work-family conflict. There are many consequences regarding burden and strain; however, burnout stands out the most. In contrast, reconciliation of work and family life and needs can be successful. The key element is empowerment of women doctors. The foremost necessary systemic solution is the reinforcement of general practitioners in primary health care and their understanding of the specialisation training scheme with more flexible possibilities for time adaptations of specialist training. PMID- 26821534 TI - Interactions of problematic mobile phone use and psychopathological symptoms with unintentional injuries: a school-based sample of Chinese adolescents. AB - BACKGROUND: Unintentional injuries are a major contributor to morbidity and mortality in adolescents. Mobile phone use in certain circumstances (e.g., driving, cycling, walking) and mental health conditions are risk factors for unintentional injury. However, research on the interactions between problematic mobile phone use (PMPU) and psychopathological symptoms in unintentional injuries is limited. The present study aimed to determine the prevalence of unintentional injuries (road traffic injuries, pedestrian collisions, and falls) and examined interactions of PMPU and psychopathological symptoms with unintentional injuries in a school-based sample of Chinese adolescents. METHODS: A total of 14,221 students (6915 middle school students and 7306 high school students) were randomly selected from 32 schools in four cities in China in 2012. The sample comprised 6712 boys and 7509 girls with a mean age of 15.12 years (standard deviation 1.89 years). PMPU, psychopathological symptoms, and unintentional injuries were measured with validated instruments. Chi-square tests and multivariable logistic regression were used to analyze the rates of unintentional injuries, the relationship with PMPU and psychopathological symptoms, and the interactions of PMPU and psychopathological symptoms with unintentional injuries. RESULTS: The prevalence of road traffic injuries, pedestrian collisions, and falls were 4.9, 16.2, and 10.1 %, respectively. The rates of unintentional injuries were higher among students with PMPU and psychopathological symptoms. Interaction analysis indicated that psychopathological symptoms were associated with a greater increase in the likelihood of unintentional injuries for adolescents with PMPU than for those without PMPU. CONCLUSIONS: The findings indicate that unintentional injuries in adolescents are an important public health issue in China that merit further research. Intervention programs must consider the adolescents' behavioral and psychological health. PMID- 26821535 TI - Treatment of Gram-negative pneumonia in the critical care setting: is the beta lactam antibiotic backbone broken beyond repair? AB - Beta-lactam antibiotics form the backbone of treatment for Gram-negative pneumonia in mechanically ventilated patients in the intensive care unit. However, this beta-lactam antibiotic backbone is increasingly under pressure from emerging resistance across all geographical regions, and health-care professionals in many countries are rapidly running out of effective treatment options. Even in regions that currently have only low levels of resistance, the effects of globalization are likely to increase local pressures on the beta lactam antibiotic backbone in the near future. Therefore, clinicians are increasingly faced with a difficult balancing act: the need to prescribe adequate and appropriate antibiotic therapy while reducing the emergence of resistance and the overuse of antibiotics. In this review, we explore the burden of Gram negative pneumonia in the critical care setting and the pressure that antibiotic resistance places on current empiric therapy regimens (and the beta-lactam antibiotic backbone) in this patient population. New treatment approaches, such as systemic and inhaled antibiotic alternatives, are on the horizon and are likely to help tackle the rising levels of beta-lactam antibiotic resistance. In the meantime, it is imperative that the beta-lactam antibiotic backbone of currently available antibiotics be supported through stringent antibiotic stewardship programs. PMID- 26821536 TI - Membrane roughness as a sensitive parameter reflecting the status of neuronal cells in response to chemical and nanoparticle treatments. AB - BACKGROUND: Cell membranes exhibit abundant types of responses to external stimulations. Intuitively, membrane topography should be sensitive to changes of physical or chemical factors in the microenvironment. We employed the non interferometric wide-field optical profilometry (NIWOP) technique to quantify the membrane roughness of living neuroblastoma cells under various treatments that could change the mechanical properties of the cells. RESULTS: The membrane roughness was reduced as the neuroblastoma cell was treated with paclitaxel, which increases cellular stiffness by translocating microtubules toward the cell membranes. The treatment of positively charged gold nanoparticles (AuNPs) showed a similar effect. In contrast, the negatively charged AuNPs did not cause significant changes of the membrane roughness. We also checked the membrane roughness of fixed cells by using scanning electron microscopy (SEM) and confirmed that the membrane roughness could be regarded as a parameter reflecting cellular mechanical properties. Finally, we monitored the temporal variations of the membrane roughness under the treatment with a hypertonic solution (75 mM sucrose in the culture medium). The membrane roughness was increased within 1 h but returned to the original level after 2 h. CONCLUSIONS: The results in the present study suggest that the optical measurement on membrane roughness can be regarded as a label-free method to monitor the changes in cell mechanical properties or binding properties of nanoparticles on cell surface. Because the cells were left untouched during the measurement, further tests about cell viability or drug efficacy can be done on the same specimen. Membrane roughness could thus provide a quick screening for new chemical or physical treatments on neuronal cells. PMID- 26821537 TI - Right ventricular systolic dysfunction and remodelling in Nigerians with peripartum cardiomyopathy: a longitudinal study. AB - BACKGROUND: The literature on right ventricular systolic dysfunction (RVSD) in peripartum cardiomyopathy (PPCM) patients is scanty, and it appears that RV reverse remodelling in PPCM has not been previously described. This study thus aimed to assess RVSD and remodelling in a cohort of PPCM patients in Kano, Nigeria. METHODS: A longitudinal study carried out in 3 referral hospitals in Kano, Nigeria. Consecutive PPCM patients who had satisfied the inclusion criteria were recruited and followed up for 12 months. RVSD was defined as the presence of either tricuspid annular plane systolic excursion (TAPSE) <16 mm or peak systolic wave (S') tissue Doppler velocity of RV free wall <10 cm/s. For the purpose of this study, recovery of RV systolic function was defined as an improvement of reduced TAPSE to >= 16 mm or S' to >= 10 cm/s, without falling to reduced levels again, during follow-up. RESULTS: A total of 45 patients were recruited over 6 months with a mean age of 26.6 +/- 7.0 years. RV systolic function recovery occurred in a total of 8 patients (8/45; 17.8%), of whom 6 (75.0%) recovered in 6 months after diagnosis. The prevalence of RVSD fell from 71.1% at baseline to 36.4% at 6 months (p = 0.007) and 18.8% at 1 year (p = 0.0008 vs baseline; p = 0.41 vs 6 month). Patients with RVSD had higher serum creatinine, and TAPSE accounted for 19.2% (p = 0.008) of the variability of serum creatinine at 6 months. Although 83.3% of the deceased had RVSD, it didn't predict mortality in the regression models (p > 0.05). CONCLUSION: RVSD and reverse remodelling were common in Nigerians with PPCM, in whom the first 6 months after diagnosis seem to be critical for RV recovery and survival. PMID- 26821538 TI - Dexmedetomidine and ketamine show distinct patterns of cell degeneration and apoptosis in the developing rat neonatal brain. AB - OBJECTIVE: Early exposure to common anesthetic and sedative agents causes widespread brain cell degeneration and apoptosis in the developing rat brain, associated with persistent learning deficits in rats. This study was designed to determine whether the alpha2 adrenergic receptor agonist, dexmedetomidine, produces brain cell degeneration and apoptosis in postnatal day-7 rats in the same brain areas when compared to ketamine. METHODS: Systemic saline, ketamine 20 mg/kg, or dexmedetomidine at 30 or 45 MUg/kg were given six times to postnatal day 7 rats (n = 6/group) every 90 min. Twenty-four hours after the initial injection, brain regions were processed and analyzed for cell degeneration using the silver stain and for apoptosis using activated caspase-3 immunohistochemistry. RESULTS: Exposure to ketamine resulted in significant cellular degeneration and apoptosis in limbic brain regions, but nonsignificant changes in primary sensory brain regions. In contrast, dexmedetomidine produced significant cellular degeneration and apoptosis in primary sensory brain regions, but nonsignificant changes in limbic regions. CONCLUSIONS: These data show that ketamine and dexmedetomidine result in anatomically distinct patterns of cell degeneration and apoptosis in the brains of 7-day-old rat pups. The meaning and the clinical significance of these findings remain to be established. PMID- 26821539 TI - Marinagarivorans algicola gen. nov., sp. nov., isolated from marine algae. AB - Two novel agar-degrading, Gram-stain-negative, motile, heterotrophic, facultatively anaerobic and pale yellow-pigmented bacterial strains, designated Z1T and JL1, were isolated from marine algae Gelidium amansii (Lamouroux) and Gracilaria verrucosa, respectively. Growth of the isolates was optimal at 28-30 degrees C, pH 7.0-7.5 and with 2-3 % (w/v) NaCl. Both strains contained Q-8 as the sole respiratory quinone. The major cellular fatty acids in strain Z1T were C18 : 1omega7c, C16 : 0 and summed feature 3 (C16 : 1omega7c and/or iso-C15 : 0 2 OH). The predominant polar lipids in strain Z1T were phosphatidylethanolamine, phosphatidylglycerol and an aminolipid. The genomic DNA G+C content of both strains was 45.1 mol%. Strains Z1T and JL1 were closely related, with 99.9 % 16S rRNA gene sequence similarity. The average nucleotide identity (ANI) value between strains Z1T and JL1 was 99.3 %. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains Z1T and JL1 form a distinct phyletic line within the class Gammaproteobacteria, with less than 92.3 % similarity to their closest relatives. Based on data from the current polyphasic study, the isolates are proposed to belong to a novel species of a new genus designated Marinagarivorans algicola gen. nov., sp. nov. The type strain of the type species is Z1T ( = ATCC BAA-2617T = CICC 10859T). PMID- 26821540 TI - Paraproteinemic neuropathy: a practical review. AB - The term paraproteinemic neuropathy describes a heterogeneous set of neuropathies characterized by the presence of homogeneous immunoglobulin in the serum. An abnormal clonal proliferation of B-lymphocytes or plasma cells, which may or may not occur in the context of a hematologic malignancy, produces the immunoglobulins in excess. If malignancy is identified, treatment should be targeted to the neoplasm. Most cases, however, occur as monoclonal gammopathy of undetermined significance. Few prospective, randomized, placebo-controlled trials are available to inform the management of paraproteinemic neuropathies. Clinical experience combined with data from smaller, uncontrolled studies provide a basis for recommendations, which depend on the specific clinical setting in which the paraprotein occurs. In this review, we provide a clinically practical approach to diagnosis and management of such patients. PMID- 26821541 TI - Ethnopharmacobotanical study on the medicinal plants used by herbalists in Sulaymaniyah Province, Kurdistan, Iraq. AB - BACKGROUND: Medicinal plants still play an important role in the Kurdish community. Sulaymaniyah Province in South Kurdistan (Iraq) has a great diversity of plants, including medicinal plants, yet very few scattered ethnobotanical studies conducted in Kurdistan are available in the scientific literature. Thus the study of Kurdish ethnobotany may be crucial for understanding local medicinal plant uses and their relationships to surrounding areas. Therefore, the objective of this investigation was to document traditional medicinal plant uses among healers of southern Kurdistan. METHODS: An ethnobotanical survey was conducted to document traditional knowledge on medicinal plants uses among traditional healers in the Province of Sulaymaniyah during 2014 and 2015. The data were collected by interviewing 45 traditional healers (36 males and 9 females between the ages of 25 and 80 years) who retain traditional knowledge on medicinal plants. Furthermore, the use value (UV) of taxa was determined and informant consensus factor (ICF) was calculated for the medicinal plants included in the study. Further analysis was carried out to compare the field data with the Kurdish ethnobotanical literature. RESULTS: The present study found a total of sixty-six plant species, belonging to sixty-three genera within thirty-four plant families, used to treat ninghty-nine different types of ailments and diseases. The most important family was Lamiaceae (7 species), followed by Apiaceae, Asteraceae, and Fabaceae (6 species each). The most frequently used parts were leaves (46 %), followed by flowers (15 %), and seeds (10 %). The most common preparation method was decoction (68 %), whereas few taxa were consumed as a vegetable (13 %) or ingested in powder form (10 %). The respiratory issues category had the highest ICF value (0.68), followed by inflammations and women's diseases (0.58 and 0.54, respectively). The highest UVs were recorded for the species Zingiber officinale (0.48), Matricaria chamomilla (0.37), Adiantum capillus-veneris (0.31), Thymus vulgaris (0.31) and Pimpinella anisum (0.31). A comparison with previous ethnobotanical studies conducted in Kurdistan (especially within the territory of present-day Turkey) and surrounding areas showed that several medicinal plant reports recorded in the current investigation are new to Kurdish ethnomedicine, and that they have possibly been influenced by other scholarly medical traditions. CONCLUSIONS: The present study demonstrates that the area is rich in medicinal plant knowledge. The information reported by the traditional healers of this region is invaluable for further research in the field of cross-cultural ethnobotany and ethnopharmacology. PMID- 26821542 TI - Epileptic Encephalopathy in Childhood: A Stepwise Approach for Identification of Underlying Genetic Causes. AB - Epilepsy is one of the most common neurological disorders in childhood. Epilepsy associated with global developmental delay and cognitive dysfunction is defined as epileptic encephalopathy. Certain inherited metabolic disorders presenting with epileptic encephalopathy can be treated with disease specific diet, vitamin, amino acid or cofactor supplementations. In those disorders, disease specific therapy is successful to achieve good seizure control and improve long-term neurodevelopmental outcome. For this reason, intractable epilepsy with global developmental delay or history of developmental regression warrants detailed metabolic investigations for the possibility of an underlying treatable inherited metabolic disorder, which should be undertaken as first line investigations. An underlying genetic etiology in epileptic encephalopathy has been supported by recent studies such as array comparative genomic hybridization, targeted next generation sequencing panels, whole exome and whole genome sequencing. These studies report a diagnostic yield up to 70%, depending on the applied genetic testing as well as number of patients enrolled. In patients with epileptic encephalopathy, a stepwise approach for diagnostic work-up will help to diagnose treatable inherited metabolic disorders quickly. Application of detailed genetic investigations such as targeted next generation sequencing as second line and whole exome sequencing as third line testing will diagnose underlying genetic disease which will help for genetic counseling as well as guide for prenatal diagnosis. Knowledge of underlying genetic cause will provide novel insights into the pathogenesis of epileptic encephalopathy and pave the ground towards the development of targeted neuroprotective treatment strategies to improve the health outcome of children with epileptic encephalopathy. PMID- 26821543 TI - Autoinflammatory Syndromes in Children. AB - Systemic autoinflammatory diseases are rare disorders of innate immunity which usually present in childhood with recurrent or continuous attacks of fever and systemic inflammation. The discovery of the genetic defect underlying Familial Mediterranean fever in 1997 has proved exceptionally informative about the innate immune system and the regulation of pro inflammatory cytokines particularly IL-1. Although extremely rare, systemic autoinflammatory diseases are important to recognise as many can now be completely controlled by long term drug therapies. Diagnosis relies on clinical suspicion followed by genetic testing. This review will focus on the main systemic autoinflammatory diseases. PMID- 26821544 TI - Study of Acute Exogenous Lipoid Pneumonia. AB - OBJECTIVE: To analyze the clinical and imagenological characteristics of acute Exogenous lipoid pneumonia (ELP), explore its risk factors, and assess the potential role of multiple bronchoalveolar lavages (BALs) and steroid therapy in the treatment of children with acute ELP. METHODS: Between May 2011 and July 2014, 33 pediatric patients with pneumonia caused by aspiration of oil-based substances were admitted to the Guangzhou Women and Children's Medical Center, Guangdong, China. Data on the demographics of these patients, as well as that on clinical presentations, imagenological characteristics, history of ingestion, laboratory observations, treatment protocol, response to therapy, BAL findings, and treatment outcomes were collected. RESULTS: The study group consisted of 23 boys (69.7 %) and 10 girls (30.3 %), with ages ranging from 4 mo to 4 y. They were admitted to the hospital 2 h to 13 d after ingesting the oil-based substance. By the time of admission, most patients presented with respiratory distress and other symptoms, including tachypnea (n = 21), cough (n = 25), mild fever (n = 18), progressive dyspnea (n = 12), and pneumorrhagia (n = 5); six patients received mechanical ventilation because of complicated respiratory distress syndrome. The most common laboratory observations were leukocytosis (25 of 33, 75.8 %), neutrophilia (23 of 33, 69.7 %), and anemia (8 of 33, 24.2 %). Serum biochemical examination showed elevated sedimentation rates (24 of 33, 72.7 %), lactate dehydrogenase levels (18 of 33, 54.5 %), and C-reactive protein levels (17 of 33, 51.5 %). The most common finding on computed tomography (CT) scans was areas of consolidation. Within the follow-up duration of 2 wk to 6 mo, all patients with clinical symptoms of ELP experienced remission, and none died. The CT scans of most of the cases were normal by 1 to 3 mo, except for two patients who showed complete improvement 6 mo after treatment. CONCLUSIONS: It was found that multiple BALs combined with steroid therapy result in significant improvement of clinical, radiologic, and laboratory parameters in children with acute ELP. Further, some traditional practices may predispose children to ELP, even in the absence of underlying risk factors. Finally, pneumorrhagia and acute respiratory distress syndrome may be the main complications of acute ELP in children. PMID- 26821545 TI - Hemophagocytic Lymphohistiocytosis Associated with Hepatitis A and Hepatitis E Co infection. PMID- 26821546 TI - The Radiograph of the Pelvis as a Window to Skeletal Dysplasias. AB - Skeletal dysplasias are disorders of bone formation. There are many dysplasias that have been identified and studied over the years and long lists of radiological features have been documented; it is not possible to remember all of them, most of which are common to more than one dysplasia. This article is about a practical approach to the radiological diagnosis of skeletal dysplasias by viewing only a few radiographs rather than the entire skeletal survey. The radiographs that are to be studied are AP view of the pelvis, dorsolumbar spine- AP and lateral view and both hands PA view, in that order. The skull lateral view and both knees AP view are sometimes required. The authors advice to set out with the pelvis that provides information of not only the pelvic bones but also parts of the lumbar spine and the upper ends of the femur including their epiphyses, metaphyses and a part of the diaphyses. Sometimes the diagnosis is reached with only this one radiograph, as in achondroplasia or it may indicate a group like mucopolysaccharidoses which can be sorted out with radiographs of the spine and hands or the upper part of the femur can provide a cue to epiphyseal and metaphyseal dysplasias. Gamuts and atlases can be consulted for the rare dysplasias. PMID- 26821547 TI - Serum Vitamin D Levels in Children with Recurrent Respiratory Infections and Chronic Cough. AB - OBJECTIVES: To evaluate serum vitamin D levels in cases of recurrent respiratory infections and chronic cough and to investigate the effect of vitamin D therapy on recurrence of the diseases. METHODS: This prospective observational study was performed by comparing serum vitamin D levels in children with recurrent respiratory infections, chronic cough and healthy children. One-hundred-one children with chronic cough, ninety-eight children with recurrent respiratory infections and one-hundred-twenty-four healthy children were enrolled in the study. A structured questionnaire was completed to collect data on demography, diet, duration of breastfeeding, vitamin D supplementation and family history for allergic diseases. In patients with low serum vitamin D levels (<20 ng/ml), vitamin D therapy was administered in addition to conventional treatment for the diseases. Patients were followed up for 6 mo and their complaints were evaluated. RESULTS: Mean serum 25(OH) vitamin D level in the recurrent respiratory infections group was 11.97 +/- 4.04 ng/ml, chronic cough group was 13.76 +/- 4.81 ng/ml and control group was 31.91 +/- 18.79 ng/ml. Comparison of serum 25(OH) vitamin D levels between the study groups revealed a statistically significant difference (p < 0.05). 25(OH)D deficiency in children was associated with increased frequency of recurrent respiratory infections and chronic cough. CONCLUSIONS: To conclude, administration of supplementary vitamin D may be useful in the treatment and preventation of recurrent respiratory infections and chronic cough. PMID- 26821548 TI - Decreasing Risky Behavior on Social Network Sites: The Impact of Parental Involvement in Secondary Education Interventions. AB - Teenagers face significant risks when using increasingly popular social network sites. Prevention and intervention efforts to raise awareness about these risks and to change risky behavior (so-called "e-safety" interventions) are essential for the wellbeing of these minors. However, several studies have revealed that while school interventions often affect awareness, they have only a limited impact on pupils' unsafe behavior. Utilizing the Theory of Planned Behavior and theories about parental involvement, we hypothesized that involving parents in an e-safety intervention would positively influence pupils' intentions and behavior. In a quasi-experimental study with pre- and post-test measures involving 207 pupils in secondary education, we compared the impact of an intervention without parental involvement with one that included active parental involvement by means of a homework task. We found that whereas parental involvement was not necessary to improve the intervention's impact on risk awareness, it did change intentions to engage in certain unsafe behavior, such as posting personal and sexual information on the profile page of a social network site, and in reducing existing problematic behavior. This beneficial impact was particularly evident for boys. These findings suggest that developing prevention campaigns with active parental involvement is well worth the effort. Researchers and developers should therefore focus on other efficient strategies to involve parents. PMID- 26821550 TI - The Elnady Technique: An innovative, new method for tissue preservation. AB - At the Faculty of Veterinary Medicine, Cairo University, there is an increasing number of students but a limited availability of animal cadavers used for dissection, and student exposure to formalin is a known hazard. In order to address these challenges, a new method for tissue preservation was developed, the "Elnady Technique." This method is a modified form of plastination, where the chemicals used are not patented, are inexpensive and locally available, and the process is performed at room temperature. The produced specimens are realistic, durable, have no offensive odor, and are dry, soft and flexible. They can be used to replace the use of animals killed for teaching basic anatomy, embryology, pathology, parasitology and forensic medicine. They have great potential to support training in clinical skills and surgery, including for clinical examination, endoscopy, surgical sutures, and obstetrics simulation. PMID- 26821549 TI - Acinetobacter baumannii in critically ill patients: Molecular epidemiology, clinical features and predictors of mortality. AB - INTRODUCTION: The main aim of this study was to assess changes in the epidemiology and clinical presentation of Acinetobacter baumannii over a 10-year period, as well as risk factors of mortality in infected patients. METHOD: Prospective, multicentre, hospital-based cohort studies including critically ill patients with A. baumannii isolated from any clinical sample were included. These were divided into a first period ("2000 study") (one month), and a second period ("2010 study") (two months). Molecular typing was performed by REP-PCR, PFGE and MSLT. The primary endpoint was 30-day mortality. RESULTS: In 2000 and 2010, 103 and 108 patients were included, and the incidence of A. baumannii colonization/infection in the ICU decreased in 2010 (1.23 vs. 4.35 cases/1000 patient-days; p<0.0001). No differences were found in the colonization rates (44.3 vs. 38.6%) or infected patients (55.7 vs. 61.4%) in both periods. Overall, 30-day mortality was similar in both periods (29.1 vs. 27.8%). The rate of pneumonia increased from 46.2 in 2000 to 64.8% in 2010 (p<0.001). Performing MSLT, 18 different sequence types (ST) were identified (18 in 2000, 8 in 2010), but ST2 and ST79 were the predominant clones. ST2 isolates in the ICU increased from 53.4% in the year 2000 to 73.8% in 2010 (p=0.002). In patients with A. baumannii infection, the multivariate analysis identified appropriate antimicrobial therapy and ST79 clonal group as protective factors for mortality. CONCLUSIONS: At 10 years of the first analysis, some variations have been observed in the epidemiology of A. baumannii in the ICU, with no changes in mortality. Epidemic ST79 clone seems to be associated with a better prognosis and adequate treatment is crucial in terms of survival. PMID- 26821551 TI - Knowledge and Attitudes Toward Mandatory Premarital Screening Among University Students in North Jordan. AB - A mandatory National Premarital Thalassemia Screening Program was implemented in Jordan in 2004. This cross-sectional study aimed to assess the knowledge and attitudes of university students in North Jordan toward this program. Data was collected from 542 students from four universities (two public and two private universities) located in North Jordan, using a structured questionnaire. Results of t-test and analysis of variance (ANOVA) showed that while respondents had adequate knowledge of and positive attitudes toward the premarital screening program, there was still a lack of knowledge about the disease itself. Nearly half the respondents were under the impression that beta-thalassemia (beta-thal) is a disease that can be treated simply. One-third of the respondents believed that if both partners were carriers of beta-thal they should proceed with marriage. Negative attitude was revealed when many respondents believed that diagnosing a family member as a carrier affects other family members' future marriage opportunities. Significant associations were detected between the knowledge scores and gender, urban/rural residence, and the university where the students were enrolled. Students in private universities showed significantly lower attitude scores. Consideration of prenatal diagnostic services as part of a beta-thal prevention program is necessary. It would also be helpful to include information about beta-thal as a preventable inherited illness with a severe debilitating impact on the family in the high school curriculum. There is also a need for social marketing of the program. PMID- 26821553 TI - Three new steroidal saponins from Helleborus thibetanus. AB - Three new steroidal saponins including two spirostanol glycosides (1-2) and one furostanol glycoside 1-sulphate (3) were isolated from the dried roots and rhizomes of Helleborus thibetanus. Structures of the compounds were determined on the basis of extensive use of 1-D and 2-D NMR experiments, together with HR-ESI MS and IR measurements, as well as the results of acid hydrolysis. Compounds 1-2 represented steroidal saponins with an unusual substitution pattern, which possessed a double bond at C-25 and were glycosylated at 1-OH. PMID- 26821552 TI - Evaluation of the relevance of surgery in a retrospective case series of patients who underwent the surgical treatment of a symptomatic spine metastasis from lung cancer. AB - BACKGROUND: The management of spine metastases is an increasing concern for spine surgeons. When considering surgery, it is crucial to ensure that its iatrogenic effects will not exceed its potential benefits, particularly in frail patients with short life expectancy. Among all prognostic factors, the primary site of cancer is the most important, lung cancer being the poorest. Although surgery has shown its effectiveness in the management of spine metastases, there is a lack of studies focusing on lung cancer alone. PURPOSE: To assess the effectiveness and safety of surgery in the management of symptomatic spine metastases from lung cancer. METHODS: We retrospectively reviewed all patients (n = 53) who underwent surgery for spine metastasis from lung cancer at the Lille University Hospital between January 2005 and December 2011. Patients for whom surgery was effective to restore or preserve ambulation, to relieve pain, and to ensure stability without severe complication were considered "surgical success". RESULTS: No patient was lost to follow-up and vital status data were available for all patients. The median survival was 2.1 months and was not influenced by the surgical success (p = 0.1766). We reported seven major complications in seven patients, including three epidural haematoma, two massive pulmonary embolisms and two deaths from cardiopulmonary failure. The surgical success rate was 49 % and on univariate analysis, the factors that have influenced the postoperative outcome were the KPS (p < 0.001), the Frankel grade (p = 0.0217) and the delay between the cancer diagnosis and the occurrence of spine metastases (p = 0.0216). CONCLUSION: A strict patient selection is required to limit the iatrogenic effect of surgery, which may alter the quality of life of these frail patients with limited life expectancy. PMID- 26821554 TI - Social disadvantage and past treatment among clients entering public alcohol and drug services in two Australian states. PMID- 26821555 TI - Correlates of health care seeking behaviour among people who inject drugs in Dar es Salaam, Tanzania. AB - BACKGROUND: People who inject drugs (PWID) suffer from a high burden of infectious disease. At the same time, they often have poor access to health care. As in other East African countries, the population of PWID is growing in Tanzania, but little is known about their contact with health care services. In this paper we examine patterns of health care use among PWID in Dar es Salaam and identify what factors are associated with regular contact with clinicians during illness. METHODS: We conducted a baseline cross-sectional study as part of a prospective cohort study involving PWID. We recruited 578 PWID, of whom 273 were newly enrolled on an integrated methadone-assisted treatment (MAT) program and 305 were community-recruited. At baseline, we interviewed the MAT program enrollees before they received services at the program clinics. We used bivariate and multiple logistic regression analyses to identify the factors associated with seeking medical care when ill. RESULTS: Only 25.4% of 578 participants reported seeing clinicians regularly when they needed medical care. Participants were more likely to see clinicians regularly if they were employed, (OR: 2.25, 95% CI: 1.28 3.98), had higher income levels (OR: 1.10, 95% CI: 1.00-1.22), were parents (OR: 1.71, 95% CI: 1.09-2.68), or knew where to seek affordable care (OR: 3.42, 95% CI: 2.12-5.52). CONCLUSION: PWID in Dar es Salaam generally did not seek health care when needed. To improve their health care seeking behaviour, it is important to advise PWID about where to seek affordable health care and to increase their income-generating skills. PMID- 26821556 TI - A qualitative study of smokers' views on brain-based explanations of tobacco dependence. AB - BACKGROUND: The role the brain plays in the creation and maintenance of tobacco dependence has become increasingly prominent in explanations of smoking that are presented to the public. The potential for brain-based explanations of smoking to influence smokers' understandings of their addiction, their sense of self efficacy, and perhaps even their treatment preferences, has been raised by some working in the addiction field. However, little empirical evidence exists in this area. METHODS: This paper reports on semi-structured interviews with 29 daily smokers. Participants were shown a brief presentation about the neuroscience of nicotine dependence. They were then queried about their awareness of the role of the brain in smoking, and the consequences of this knowledge for their understandings of smoking and their treatment preferences. RESULTS: Our results indicated that many participants displayed some awareness of the link between the brain and addiction. While there was a diversity of ideas about the potential impacts of neuroscience knowledge about smoking, there was an overall tendency to maintain pre-existing treatment preferences, and to assert individual responsibility for smoking. Emergent themes that arose were the brain as a special organ, the discourse of the "other" smoker, and the distinction between physical and psychological facets of addiction. CONCLUSION: While brain-based explanations of smoking are unlikely to revolutionise lay understandings of smoking, neuroscience information should be presented in a way that does not negate people's sense of agency and self-efficacy in relation to quitting smoking. PMID- 26821557 TI - Usefulness of multidetector-row computerized tomographic angiography for the surgical planning in stereoelectroencephalography. AB - PURPOSE: Surgical planning of depth electrode implantation in stereo-electro encephalography (SEEG) routinely uses magnetic resonance imaging (MRI) alone. Accurate visualization of arteries and veins in the vicinity of the electrode is essential to plan a safe trajectory to presumably reduce the risk of intracranial bleeding. The goal of this study was to compare multidetector row computerized tomographic angiography (MDCTA) with MRI for the visualization of vessels along each planned trajectory in patients who undergo SEEG. MATERIALS AND METHODS: Ten consecutive patients who were scheduled to undergo SEEG procedure were included. T1-weighted gadolinium-chelate enhanced MR sequence, stereotactic MDCT and MDCTA were performed after fixation of Leksell's frame. For each of the 106 planned stereotactic trajectories, the number of vessels in a 4.0mm diameter circle around the trajectory from the dura mater to the target that were visible on MDCTA were compared to that of visible vessels in the same areas on MRI. RESULTS: Ten vessels (10/106; 9.4%) were seen on MRI and 66 (66/106; 62.3%) on MDCTA (P<0.0001). All vessels visible on MRI were visible on MDCTA. The difference in number of visible vessels between the two techniques remained significant for the different lobes (i.e., frontal lobe, temporal lobe and parieto-occipital lobe). CONCLUSION: MDCTA enabled visualization of more vessels than MRI based SEEG. MDCTA may help neurosurgeons better define the trajectory of the electrode and reduce the risk of intracranial bleeding. PMID- 26821558 TI - Critical Guidelines for Health Care Workers Who Deploy to West Africa for the Ebola Response. PMID- 26821559 TI - Mg-Enriched Engineered Carbon from Lithium-Ion Battery Anode for Phosphate Removal. AB - Three Mg-enriched engineered carbons (mesocarbon microbeads, MCMB) were produced from lithium-ion battery anode using concentrated nitric acid oxidization and magnesium nitrate pretreatment. The obtained 15%Mg-MCMB, 30%Mg-MCMB, and 40%Mg MCMB have magnesium level of 10.19, 19.13, and 19.96%, respectively. FTIR spectrum shows the functional groups present on the oxidized MCMB including OH, C?O, C-H, and C-O. XRD, SEM-EDX, and XPS analyses show that nanoscale Mg(OH)2 and MgO particles were presented on the surface of the Mg-MCMB samples, which could serve as the main adsorption mechanism as to precipitate phosphate from aqueous solutions. The sorption experiments indicate that Mg modification dramatically promotes MCMB's phosphate removal ability and phosphate removal rates reach as high as 95%. Thus, modification of the spent LIBs anode could provide a novel direction of preparing wastewater adsorbent and develop an innovative way to achieve sustainable development. PMID- 26821560 TI - Revision shoulder arthroplasty: does the stem really matter? AB - BACKGROUND: The management of a failed shoulder arthroplasty represents a complex and difficult problem for the treating surgeon, with potential difficulties and complications that are related to the need to remove a well-fixed stem. The aim of this study is to compare the intraoperative complications, postoperative complications, and outcome of revisions from stemmed arthroplasties (STAs) with those from surface replacement arthroplasties (SRAs). METHODS: From 2005 to 2012, 40 consecutive revision shoulder arthroplasties were performed at our institute: 17 from STAs and 23 from SRAs. Perioperative events, operation time, blood loss, intraoperative fractures, and use of structural allograft were recorded. Clinical and radiologic outcomes were analyzed. RESULTS: Operation time, need for humeral osteotomy, need for structural allograft, and number of intraoperative fractures were significantly higher in the STA group. Blood loss, drop in hemoglobin level, need for blood transfusion, and hospitalization time were also higher in the STA group, but these differences were not statistically significant. Reoperation was performed in 3 patients in the SRA group. A significant clinical improvement was observed in both groups. The Constant score was higher in the SRA group. CONCLUSION: Revision of STAs is a more demanding procedure. The postoperative complication rate was slightly higher in the SRA group. The group with revision of SRAs showed slightly better clinical and radiographic results, but there was no statistically significant difference between the groups. PMID- 26821561 TI - Photocrosslinking of Silk Fibroin Using Riboflavin for Ocular Prostheses. AB - A novel method to photocrosslink silk fibroin protein is reported, using riboflavin (vitamin B2) as a photoinitiator and the mechanism of crosslinking is determined. Exposure of riboflavin-doped liquid silk solution to light results in the formation of a transparent, elastic hydrogel. Several applications for this new material are investigated including corneal reshaping to restore visual acuity and photolithography. PMID- 26821562 TI - Response inhibition in the parametric go/no-go task and its relation to impulsivity and subclinical psychopathy. AB - The current study utilizes the parametric go/no-go task (PGNG), a task that examines changes in inhibitory performance as executive function load increases, to examine the link between psychopathic traits, impulsivity, and response inhibition in a cohort of healthy participants. The results show that as executive function load increased, inhibitory ability decreased. High scores on the Cognitive Complexity subscale of the Barratt Impulsivity Scale (BIS-11) predict poor inhibitory ability in the PGNG. Similarly, high scores on the Psychopathy Personality Inventory-Revised (PPI-R) Blame Externalization subscale predict response inhibition deficits in the PGNG, which loads more on the executive functions than the standard go/no-go task. The remaining BIS-11 as well as PPI-R subscales did not interact with inhibitory performance in the PGNG highlighting the specificity of associations between aspects of personality and impulsivity with inhibitory performance as cognitive load is increased. These data point towards the sensitivity of the PGNG in studying response inhibition in the context of highly impulsive populations and its utility as a measure of impulsivity. PMID- 26821563 TI - Social Media Use in Pediatric Dermatology. AB - Social media is predicted to become increasingly important in dermatology because of its potential to serve as a platform for public health campaigns, aid in participant recruitment for clinical trials, increase public engagement in health care, and facilitate scientific discourse. No study of social media use in pediatric dermatology has been performed, so we analyzed the use of the seven leading social media platforms in pediatric dermatology, with a focus on patient advocacy groups, professional societies, research journals, and research institutions. We observed that 89% of patient advocacy groups, 100% of professional societies, 62.5% of research journals, and 0% of academic pediatric dermatology departments maintained one or more social media accounts. Our observations suggest that all stakeholder groups, and in particular members of the research community, have the potential to further their engagement, connections, and communications through social media. PMID- 26821564 TI - The revised guidelines of the Medical Council of India for academic promotions: Need for a rethink. PMID- 26821565 TI - Inappropriate preinjury warfarin use in trauma patients: A call for a safety initiative. AB - INTRODUCTION: Warfarin continues to be widely prescribed for a variety of conditions. It has been shown that preinjury warfarin may worsen outcomes in trauma patients. We hypothesized that a substantial proportion of injured patients seen at our institution were receiving preinjury warfarin for inappropriate indications and that a significant number of such patients had subtherapeutic or supratherapeutic international normalized ratios as well as increased mortality. MATERIALS AND METHODS: A retrospective review of registry data from a Level I trauma center was conducted for the period from January 2004 to July 2013. Included were patients aged >=22 years (based on the youngest recorded patient on warfarin in this study). Abstracted variables included patient age, Injury Severity Score (ISS), Maximum Abbreviated Injury Score for Head (MAISH), mortality, hospital length of stay (HLOS), indication(s) for anticoagulant therapy, admission Glasgow Coma Scale (GCS), and admission international normalized ratio (INR). Suitability of warfarin indication(s) was determined using the most recent American College of Chest Physicians (ACCP) Guidelines. Inappropriate warfarin administration was defined as use inconsistent with these guidelines. For outcome comparisons, a case-control design with 1:1 ratio was used, matching patients taking preinjury warfarin to a random sample of trauma patients who were not taking warfarin. Severe traumatic brain injury (sTBI) was defined as MAISH >=4. RESULTS: A total of 700 out of 14,583 patients aged >=22 years were receiving preinjury warfarin (4.8% incidence, WG). This group was age- and ISS-matched with 700 patients (4.8% total sample) who were not taking warfarin (NWG) in a total case-control sample of 1,400. The two groups were similar in age, gender, ISS, and initial GCS. According to the ACCP guidelines, 115/700 (16.4%) patients in the warfarin group were receiving anticoagulation for inappropriate indications. Nearly 65% of the patients were outside of their intended INR therapeutic window (43.4% subtherapeutic, 21.6% supratherapeutic). Overall, median HLOS was greater among patients taking preinjury warfarin (4 days vs 2 days, P < 0.010). Mortality was higher in the WG (7.4% or 52/700) than in the NWG (1.9% or 13/700, P < 0.010). Patients with sTBI in the WG had significantly greater mortality (12.8% or 34/266) than those with sTBI in the NWG (5.3% or 9/169, P < 0.013). CONCLUSION: A significant proportion of trauma patients admitted to our institution were noted to take warfarin for inappropriate indications. Moreover, many patients taking warfarin had either subtherapeutic or supratherapeutic INR. Although warfarin use did not independently predict mortality, preinjury warfarin use was associated with greater mortality and HLOS in the subset of patients with sTBI. Safety initiatives directed at better initiation and management of warfarin are needed. PMID- 26821566 TI - Molecular characterization of nucleoprotein gene of rabies virus from Maharashtra, India. AB - CONTEXT: Rabies poses a serious public health concern in developing countries such as India. AIMS: The study focuses on molecular diagnosis of street rabies virus (RABV) from human clinical specimens received from Maharashtra, India. MATERIALS AND METHODS: Nucleoprotein gene from eight (of total 20 suspected samples) rabies cases that tested positive for rabies antigen using reverse transcriptase-polymerase chain reaction (RT-PCR) were sequenced. RESULTS: Sequence analysis using basic local alignment search tool (BLAST) and multiple sequence alignment (MSA) and phylogenetic analysis showed similarity to previously reported sequences from India and those of Arctic lineages. CONCLUSIONS: The circulating RABV strains in Maharashtra, India show genetic relatedness to RABV strains reported from Indo-Arctic lineages and India-South and Japan. PMID- 26821567 TI - Towards a phylogenetic classification of Leptothecata (Cnidaria, Hydrozoa). AB - Leptothecata are hydrozoans whose hydranths are covered by perisarc and gonophores and whose medusae bear gonads on their radial canals. They develop complex polypoid colonies and exhibit considerable morphological variation among species with respect to growth, defensive structures and mode of development. For instance, several lineages within this order have lost the medusa stage. Depending on the author, traditional taxonomy in hydrozoans may be either polyp- or medusa-oriented. Therefore, the absence of the latter stage in some lineages may lead to very different classification schemes. Molecular data have proved useful in elucidating this taxonomic challenge. We analyzed a super matrix of new and published rRNA gene sequences (16S, 18S and 28S), employing newly proposed methods to measure branch support and improve phylogenetic signal. Our analysis recovered new clades not recognized by traditional taxonomy and corroborated some recently proposed taxa. We offer a thorough taxonomic revision of the Leptothecata, erecting new orders, suborders, infraorders and families. We also discuss the origination and diversification dynamics of the group from a macroevolutionary perspective. PMID- 26821568 TI - A transcription activator-like effector from Xanthomonas oryzae pv. oryzicola elicits dose-dependent resistance in rice. AB - Xanthomonas spp. reduce crop yields and quality worldwide. During infection of their plant hosts, many strains secrete transcription activator-like (TAL) effectors, which enter the host cell nucleus and activate specific corresponding host genes at effector binding elements (EBEs) in the promoter. TAL effectors may contribute to disease by activating the expression of susceptibility genes or trigger resistance associated with the hypersensitive reaction (HR) by activating an executor resistance (R) gene. The rice bacterial leaf streak pathogen X. oryzae pv. oryzicola (Xoc) is known to suppress host resistance, and no host R gene has been identified against it, despite considerable effort. To further investigate Xoc suppression of host resistance, we conducted a screen of effectors from BLS256 and identified Tal2a as an HR elicitor in rice when delivered heterologously by a strain of the closely related rice bacterial blight pathogen X. oryzae pv. oryzae (Xoo) or by the soybean pathogen X. axonopodis pv. glycines. The HR required the Tal2a activation domain, suggesting an executor R gene. Tal2a activity was differentially distributed among geographically diverse Xoc isolates, being largely conserved among Asian isolates. We identified four genes induced by Tal2a in next-generation RNA sequencing experiments and confirmed them using quantitative real-time reverse transcription-polymerase chain reaction (qPCR). However, neither individual nor collective activation of these genes by designer TAL effectors resulted in HR. A tal2a knockout mutant of BLS256 showed virulence comparable with the wild-type, but plasmid-based overexpression of tal2a at different levels in the wild-type reduced virulence in a directly corresponding way. Overall, the results reveal that host resistance suppression by Xoc plays a critical role in pathogenesis. Further, the dose dependent avirulence activity of Tal2a and the apparent lack of a single canonical target that accounts for HR point to a novel, activation domain dependent mode of action, which might involve, for example, a non-coding gene or a specific pattern of activation across multiple targets. PMID- 26821569 TI - World Health Organization and emergency health: if not now, when? PMID- 26821570 TI - Chronic Administration of Catestatin Improves Autonomic Function and Exerts Cardioprotective Effects in Myocardial Infarction Rats. AB - Catestatin (CST), which is emerging as a novel cardiac modulator, can protect the heart against excessive sympathetic drive in hypertensive cardiomyopathy. The aim of this study is to investigate whether exogenous CST decreases excessive cardiac sympathetic drive and improves autonomic function and exerts cardioprotective effects in myocardial infarction (MI) rats. Rats were divided into a sham group, MI group, and MI plus CST (MI + CST) group. Four weeks later, the autonomic function of the animals was assessed by analyzing heart rate variability (HRV) and measuring plasma catecholamine. Cardiac function was evaluated via echocardiography. Electrophysiological characteristics were assessed in Langendorff-perfused hearts. Compared to the MI group, the chronic administration of CST significantly increased the standard deviation of normal-normal intervals (P < .01) and low-frequency (LF) and high-frequency (HF) HRV and decreased the ratio of LF-HF HRV (P < .01 for all). Additionally, the level of plasma catecholamine was reduced in the MI + CST group compared to the MI group (P < .01). Treatment with CST significantly increased ejection fraction (EF) and fraction shorting (FS) and significantly decreased the left ventricular end systolic diameter and left ventricular end-diastolic diameter at 28 days postmyocardial infraction (P < .05 for all). After MI, the ventricular repolarization duration, such as QTc intervals and action potential duration (APD) at 90% repolarization, was prolonged, and this prolongation could be decreased by CST (P < .05 for all). The CST also increased the threshold of ADP alternans (P < .01). Moreover, ventricular arrhythmias were induced in 83% of the MI group but only 33% of the MI + CST group (P < .05). These results suggested that the chronic administration of CST plays a role in cardioprotection in MI rats, which may function by decreasing the cardiac sympathetic drive and improving autonomic function. PMID- 26821573 TI - Targeting the Achilles' heel of adult living donor liver transplant: Corner sparing sutures with mucosal eversion technique of biliary anastomosis. PMID- 26821571 TI - Degradation dynamics of microRNAs revealed by a novel pulse-chase approach. AB - The regulation of miRNAs is critical to the definition of cell identity and behavior in normal physiology and disease. To date, the dynamics of miRNA degradation and the mechanisms involved in remain largely obscure, in particular, in higher organisms. Here, we developed a pulse-chase approach based on metabolic RNA labeling to calculate miRNA decay rates at genome-wide scale in mammalian cells. Our analysis revealed heterogeneous miRNA half-lives, with many species behaving as stable molecules (T1/2> 24 h), while others, including passenger miRNAs and a number (25/129) of guide miRNAs, are quickly turned over (T1/2= 4-14 h). Decay rates were coupled with other features, including genomic organization, transcription rates, structural heterogeneity (isomiRs), and target abundance, measured through quantitative experimental approaches. This comprehensive analysis highlighted functional mechanisms that mediate miRNA degradation, as well as the importance of decay dynamics in the regulation of the miRNA pool under both steady-state conditions and during cell transitions. PMID- 26821572 TI - Comparison of Self-report and Performance-Based Balance Measures for Predicting Recurrent Falls in People With Parkinson Disease: Cohort Study. AB - BACKGROUND: Balance confidence and fear of falling are factors associated with recurrent falls in people with Parkinson disease (PD). However, the accuracy for predicting falls on the basis of self-report measures has not been widely investigated. OBJECTIVE: The study objectives were: (1) to compare the accuracy of the Activities-specific Balance Confidence Scale (ABC) and the Falls Efficacy Scale-International (FES-I) with that of the Berg Balance Scale (BBS), Dynamic Gait Index (DGI), Functional Reach Test (FRT), and Timed "Up & Go" Test (TUG) for predicting recurrent falls in people with PD and (2) to explore the ability of combinations of up to 3 tests to predict recurrent falls. DESIGN: This was a prospective cohort study involving 225 people with PD. METHODS: Participants were assessed with the ABC, FES-I, BBS, FRT, TUG, and DGI. Participants who reported 2 or more falls in the 12-month follow-up period were classified as recurrent fallers. Areas under the receiver operating characteristic curves were determined, and the Akaike information criterion was used to select the best predictive model. RESULTS: Eighty-four participants (37.3%) were classified as recurrent fallers. Areas under the receiver operating characteristic curves for the ABC, FES-I, TUG, FRT, DGI, and BBS were 0.73, 0.74, 0.72, 0.74, 0.76, and 0.79, respectively. Two-test models provided additional discriminating ability compared with individual measures and had Akaike information criterion values similar to those of 3-test models, particularly the combination of the BBS with the FES-I. LIMITATIONS: The lack of an external validation sample was a limitation of this study. CONCLUSIONS: The ABC and FES-I demonstrated moderate accuracy in predicting recurrent falls and a predictive ability similar to that of performance-based balance measures, especially the FRT and the TUG. Two-test models showed performance similar to that of 3-test models, suggesting that a combination of 2 measures may improve the ability to predict recurrent falls in people with PD. Specifically, the combination of the BBS with the FES-I may be considered. PMID- 26821574 TI - A comparison of the ability of the human IgG1 allotypes G1m3 and G1m1,17 to stimulate T-cell responses from allotype matched and mismatched donors. AB - The immunogenicity of clinically administered antibodies has clinical implications for the patients receiving them, ranging from mild consequences, such as increased clearance of the drug from the circulation, to life-threatening effects. The emergence of methods to engineer variable regions resulting in the generation of humanised and fully human antibodies as therapeutics has reduced the potential for adverse immunogenicity. However, due to differences in sequence referred to as allotypic variation, antibody constant regions are not homogeneous within the human population, even within sub-classes of the same immunoglobulin isotype. For therapeutically administered antibodies, the potential exists for an immune response from the patient to the antibody if the allotype of patient and antibody do not match. Allotypic distribution in the human population varies within and across ethnic groups making the choice of allotype for a therapeutic antibody difficult. This study investigated the potential of human IgG1 allotypes to stimulate responses in human CD4(+) T cells from donors matched for homologous and heterologous IgG1 allotypes. Allotypic variants of the therapeutic monoclonal antibody trastuzumab were administered to genetically defined allotypic matched and mismatched donor T cells. No significant responses were observed in the mismatched T cells. To investigate the lack of T-cell responses in relation to mismatched allotypes, HLA-DR agretopes were identified via MHC associated peptide proteomics (MAPPs). As expected, many HLA-DR restricted peptides were presented. However, there were no peptides presented from the sequence regions containing the allotypic variations. Taken together, the results from the T-cell assay and MAPPs assay indicate that the allotypic differences in human IgG1 do not represent a significant risk for induction of immunogenicity. PMID- 26821575 TI - Exploring De Novo metabolic pathways from pyruvate to propionic acid. AB - Industrial biotechnology provides an efficient, sustainable solution for chemical production. However, designing biochemical pathways based solely on known reactions does not exploit its full potential. Enzymes are known to accept non native substrates, which may allow novel, advantageous reactions. We have previously developed a computational program named Biological Network Integrated Computational Explorer (BNICE) to predict promiscuous enzyme activities and design synthetic pathways, using generalized reaction rules curated from biochemical reaction databases. Here, we use BNICE to design pathways synthesizing propionic acid from pyruvate. The currently known natural pathways produce undesirable by-products lactic acid and succinic acid, reducing their economic viability. BNICE predicted seven pathways containing four reaction steps or less, five of which avoid these by-products. Among the 16 biochemical reactions comprising these pathways, 44% were validated by literature references. More than 28% of these known reactions were not in the BNICE training dataset, showing that BNICE was able to predict novel enzyme substrates. Most of the pathways included the intermediate acrylic acid. As acrylic acid bioproduction has been well advanced, we focused on the critical step of reducing acrylic acid to propionic acid. We experimentally validated that Oye2p from Saccharomyces cerevisiae can catalyze this reaction at a slow turnover rate (10(-3) s(-1) ), which was unknown to occur with this enzyme, and is an important finding for further propionic acid metabolic engineering. These results validate BNICE as a pathway-searching tool that can predict previously unknown promiscuous enzyme activities and show that computational methods can elucidate novel biochemical pathways for industrial applications. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:303-311, 2016. PMID- 26821577 TI - Epidemiology of Eye-Related Emergency Department Visits. AB - IMPORTANCE: Determining the epidemiology of eye-related emergency department (ED) visits on a national level can assist policymakers in appropriate allocation of resources. OBJECTIVE: To study ED visits related to ocular conditions for all age groups across the United States. DESIGN, SETTING, AND PARTICIPANTS: Nationally representative data from the US Nationwide Emergency Department Sample (NEDS) were used to analyze ED visits from January 1, 2006, to December 31, 2011 (6 years). All patients with eye problems presenting to EDs across the United States were eligible for inclusion. A weighted count of 11 929 955 ED visits were categorized as possibly emergent (emergent), unlikely to be emergent (nonemergent), or could not be determined. Data were analyzed from March 1 to May 30, 2015. MAIN OUTCOMES AND MEASURES: Population-based incidence rates of eye related ED visits, incidence rates of eye injuries, relative proportions of emergent vs nonemergent eye-related ED visits among different age groups, and independent factors associated with emergent vs nonemergent visits. RESULTS: From 2006 to 2011, 11 929 955 ED visits (male patients, 54.2%; mean [SD] age, 31 [22] years) for ocular problems across the United States were categorized as emergent (41.2%), nonemergent (44.3%), or could not determine (14.5%). Corneal abrasions (13.7%) and foreign body in the external eye (7.5%) were the leading diagnoses in the emergent category. More than 4 million visits were for conjunctivitis (28.0%), subconjunctival hemorrhages (3.0%), and styes (3.8%). Emergent visits were significantly more likely to occur among males (odds ratio [OR], 2.00; 95% CI, 2.00-2.01), patients in the highest income quartile (OR, 1.47; 95% CI, 1.46 1.49), older patients (OR, 2.38; 95% CI, 2.38-2.44), and patients with private insurance (OR, 1.29; 95% CI, 1.28-1.30). Mean annual inflation-adjusted charges for all eye-related ED visits totaled $2.0 billion. CONCLUSIONS AND RELEVANCE: Across the United States, nonemergent conditions accounted for almost half of all eye-related ED visits. Interventions to facilitate management of these cases outside the ED could make ED resources more available for truly emergent ophthalmic and medical issues. PMID- 26821578 TI - Fecal Transplantation for Clostridium Difficile-"All Stool May Not Be Created Equal". AB - Clostridium difficile is a gram-positive bacterium that is recognized as a causative organism of pseudomembranous enterocolitis. This infection has become a major public health challenge and is a source of considerable morbidity and mortality in those infected. We present a 62-year-old African American female with a long history of HIV infection, who presented with abdominal pain and continuous diarrhea due to pseudomembranous colitis. After failing multiple episodes of conventional therapy, it was decided to treat her with fecal microbiota transplantation. Fecal microbiota transplantation was given on 3 separate occasions from a biological-related donor without success. It was only after a fourth transplant was done with a nonrelated donor that the patient resolved her diarrhea within 48 hours. We suggest that fecal samples from different donors have different abilities to cure Clostridium difficile colitis in at least this immunosuppressed patient. PMID- 26821576 TI - Charged MVB protein 5 is involved in T-cell receptor signaling. AB - Charged multivesicular body protein 5 (CHMP5) has a key role in multivesicular body biogenesis and a critical role in the downregulation of signaling pathways through receptor degradation. However, the role of CHMP5 in T-cell receptor (TCR) mediated signaling has not been previously investigated. In this study, we utilized a short hairpin RNA-based RNA interference approach to investigate the functional role of CHMP5. Upon TCR stimulation, CHMP5-knockdown (CHMP5(KD)) Jurkat T cells exhibited activation of TCR downstream signaling molecules, such as PKCtheta and IKKalphabeta, and resulted in the activation of nuclear factor kappaB and the marked upregulation of TCR-induced gene expression. Moreover, we found that activator protein-1 and nuclear factor of activated T-cells transcriptional factors were markedly activated in CHMP5(KD) Jurkat cells in response to TCR stimulation, which led to a significant increase in interleukin-2 secretion. Biochemical studies revealed that CHMP5 endogenously forms high molecular-weight complexes, including TCR molecules, and specifically interacts with TCRbeta. Interestingly, flow cytometry analysis also revealed that CHMP5(KD) Jurkat T cells exhibit upregulation of TCR expression on the cell surface compared with control Jurkat T cells. Taken together, these findings demonstrated that CHMP5 might be involved in the homeostatic regulation of TCR on the cell surface, presumably through TCR recycling or degradation. Thus CHMP5 is implicated in TCR-mediated signaling. PMID- 26821579 TI - Lipopolysaccharide Delays Closure of the Rat Ductus Arteriosus by Induction of Inducible Nitric Oxide Synthase But Not Prostaglandin E2. AB - BACKGROUND: The incidence of patent ductus arteriosus is known to be higher in premature neonates with infection than in those without infection. However, the detailed mechanism has not been investigated. METHODS AND RESULTS: Lipopolysaccharide (LPS; 100 MUg/kg) was injected into timed-pregnant Wistar rats on day 18 and 19 of pregnancy. The fetuses were delivered by cesarean section on gestational day 21. Using a rapid whole-body freezing method, it was found that closure of the ductus arteriosus (DA) was significantly delayed in neonates from LPS-injected rats after birth. Histological analysis demonstrated that there was no difference in vascular remodeling of the DA. Quantitative reverse transcriptase-polymerase chain reaction analysis showed that the tumor necrosis factor alpha and inducible nitric oxide synthase (iNOS) mRNA expression level was significantly increased, but there was no difference in cyclooxygenase 2 and prostaglandin receptor, EP4, mRNA expression in the DA from LPS-injected rats. Moreover, the NOS inhibitor,Nomega-Nitro-L-arginine methyl ester hydrochloride, significantly prevented the delayed closure of the DA after birth in neonates from LPS-injected rats. CONCLUSIONS: The present study demonstrated that LPS mediated infection delayed closure of the rat DA without apparent histological changes. iNOS, but not prostaglandin E2, may play a primary role in delayed functional closure of the DA. (Circ J 2016; 80: 703-711). PMID- 26821580 TI - Factors Associated With Metabolic Syndrome That Affect Prognosis in Heart Failure Patients. PMID- 26821581 TI - Insulin Resistance as a Predictor of the Late Catch-up Phenomenon After Drug Eluting Stent Implantation. AB - BACKGROUND: Percutaneous coronary intervention (PCI) is an effective treatment for patients with ischemic heart disease. In particular, restenosis is suppressed after drug-eluting stent (DES) implantation. However, several problems remain. Previously, we reported neointimal proliferation after DES implantation, which was associated with insulin resistance (IR). The aim of the present study was to clarify whether IR is associated with mortality and major adverse cardiac and cerebrovascular events (MACCE) after 1st-generation DES implantation. METHODS AND RESULTS: We researched the clinical records of 109 patients who had undergone elective PCI and DES implantation between May 2007 and December 2010. We segregated these patients according to the value of the homeostasis model assessment of IR (HOMA-IR) into Group P (n=63; HOMA-IR >=2.5, positive) and Group N (n=46; HOMA-IR <2.5, negative), and examined the relationship between HOMA-IR and MACCE. The observation period was 7.4+/-1.6 years. There were no differences between the 2 groups in the occurrence of all-cause death, cardiac death, restenosis, myocardial infarction, stroke, heart failure, or stent thrombosis. However, the late catch-up phenomenon was significantly more common in Group P than in Group N (12.7% vs. 2.2% P=0.048). CONCLUSIONS: IR is a useful predictor of the late catch-up phenomenon after DES implantation, and improvement of IR may help to prevent the phenomenon. (Circ J 2016; 80: 657-662). PMID- 26821582 TI - Distribution of Anti-Factor Xa Activity in Patients on Edoxaban Therapy for Non Valvular Atrial Fibrillation. AB - BACKGROUND: The distribution of anti-factor Xa activity (AXA) values in non valvular atrial fibrillation (NVAF) patients on edoxaban therapy has not been fully elucidated. METHODS AND RESULTS: The steady-state trough and peak AXA values were measured in 66 NVAF patients. The trough AXA value did not differ significantly between the 60-mg and the 30-mg OD groups (0.17+/-0.13 IU/ml vs. 0.12+/-0.11 IU/ml, respectively; P=0.17). Similarly, the peak AXA value did not differ significantly between the 2 groups (1.45+/-0.81 IU/ml vs. 1.25+/-0.48 IU/ml, respectively; P=0.26). CONCLUSIONS: Recommended dosing should be followed for sufficient efficacy of edoxaban. (Circ J 2016; 80: 745-747). PMID- 26821583 TI - Three-Year Clinical Outcomes of Everolimus-Eluting Stents From the Post-Marketing Surveillance Study of Cobalt-Chromium Everolimus-Eluting Stent (XIENCE V/PROMUS) in Japan. AB - BACKGROUND: The Cobalt-Chromium Everolimus-Eluting Stent (CoCr-EES) Post marketing Surveillance (PMS) is a prospective multicenter registry designed to evaluate the safety and efficacy of XIENCE V/PROMUS everolimus-eluting stents in routine clinical practice at 47 centers representative of the clinical environment in Japan. METHODS AND RESULTS: We enrolled 2,010 consecutive patients (2,649 lesions) who underwent PCI using CoCr-EES. Clinical outcomes were evaluated for up to 3 years. Clinical follow-up was available in 1,930 patients (96%) at 3 years. Major adverse cardiovascular events (MACE) occurred in 6.8% of patients, including cardiac death (1.7%), myocardial infarction (1.5%), and clinically driven target lesion revascularization (CD-TLR, 4.2%). Late CD-TLR rate was 0.8% from 1 to 2 years, and 0.5% from 2 to 3 years. Definite or probable stent thrombosis occurred in 7 patients (0.3%) up to 1 year. There was no very late definite or probable stent thrombosis from 1 to 3 years. Significant independent predictors for MACE were hemodialysis, prior coronary intervention, triple-vessel coronary artery disease, and age >70 years. CONCLUSIONS: Three-year clinical outcomes from the CoCr-EES PMS demonstrated a low incidence of clinical events. There was no major concern about very late stent thrombosis or late catch up phenomenon in patients treated with EES in routine clinical practice in Japan. PMID- 26821584 TI - Neocortical GABA release at high intracellular sodium and low extracellular calcium: an anti-seizure mechanism. AB - In epilepsy, the GABA and glutamate balance may be disrupted and a transient decrease in extracellular calcium occurs before and during a seizure. Flow Cytometry based fluorescence activated particle sorting experiments quantified synaptosomes from human neocortical tissue, from both epileptic and non-epileptic patients (27.7% vs. 36.9% GABAergic synaptosomes, respectively). Transporter mediated release of GABA in human and rat neocortical synaptosomes was measured using the superfusion technique for the measurement of endogenous GABA. GABA release was evoked by either a sodium channel activator or a sodium/potassium ATPase inhibitor when exocytosis was possible or prevented, and when the sodium/calcium exchanger was active or inhibited. The transporter-mediated release of GABA is because of elevated intracellular sodium. A reduction in the extracellular calcium increased this release (in both non-epileptic and epileptic, except Rasmussen encephalitis, synaptosomes). The inverse was seen during calcium doubling. In humans, GABA release was not affected by exocytosis inhibition, that is, it was solely transporter-mediated. However, in rat synaptosomes, an increase in GABA release at zero calcium was only exhibited when the exocytosis was prevented. The absence of calcium amplified the sodium/calcium exchanger activity, leading to elevated intracellular sodium, which, together with the stimulation-evoked intracellular sodium increment, enhanced GABA transporter reversal. Sodium/calcium exchange inhibitors diminished GABA release. Thus, an important seizure-induced extracellular calcium reduction might trigger a transporter- and sodium/calcium exchanger-related anti-seizure mechanism by augmenting transporter-mediated GABA release, a mechanism absent in rats. Uniquely, the additional increase in GABA release because of calcium-withdrawal dwindled during the course of illness in Rasmussen encephalitis. Seizures cause high Na(+) influx through action potentials. A transient decrease in [Ca(2+)]e (seizure condition) increases GABA transporter (GAT)-mediated GABA release because of elevated [Na(+)]i. This amplifies the Sodium-Calcium-Exchanger (NCX) activity, further increasing [Na(+)]i and GABA release. The reduction in [Ca(2+)]e triggers a GAT-NCX related anti-seizure mechanism by augmenting GAT mediated GABA release. This mechanism, obvious in humans, is absent in rats. PMID- 26821585 TI - Coherent vibration and ultrafast dynamics upon bond formation in excited dimers of an Au(I) complex. AB - Au-Au bond strengthening in photoexcited dimers of an Au(I) complex is captured in solution as oscillations of femtosecond absorption signals. The subsequent dynamics, when compared to the trimer's data, confirm that the bent-to-linear structural change of the trimer occurs in the first few picoseconds. PMID- 26821586 TI - A detailed expression map of the PIN1 auxin transporter in Arabidopsis thaliana root. AB - BACKGROUND: Theauxin efflux carrier PIN1 is a key mediator of polar auxin transport in developing plant tissues. This is why factors that are supposed to be involved in auxin distribution are frequently tested in the regulation of PIN1 expression. As a result, diverse aspects of PIN1 expression are dispersed across dozens of papers entirely devoted to other specific topics related to the auxin pathway. Integration of these puzzle pieces about PIN1 expression revealed that, along with a recurring pattern, some features of PIN1 expression varied from article to article. To determine if this uncertainty is related to the specific foci of articles or has a basis in the variability of PIN1 gene activity, we performed a comprehensive 3D analysis of PIN1 expression patterns in Arabidopsis thaliana roots. RESULTS: We provide here a detailed map of PIN1 expression in the primary root, in the lateral root primordia and at the root-shoot junction. The variability in PIN1 expression pattern observed in individual roots may occur due to differences in auxin distribution between plants. To simulate this effect, we analysed PIN1 expression in the roots from wild type seedlings treated with different IAA concentrations and pin mutants. Most changes in PIN1 expression after exogenous IAA treatment and in pin mutants were also recorded in wild type but with lower frequency and intensity. Comparative studies of exogenous auxin effects on PIN1pro:GUS and PIN1pro:PIN1-GFP plants indicated that a positive auxin effect is explicit at the level of PIN1 promoter activity, whereas the inhibitory effect relates to post-transcriptional regulation. CONCLUSIONS: Our results suggest that the PIN1 expression pattern in the root meristem accurately reflects changes in auxin content. This explains the variability of PIN1 expression in the individual roots and makes PIN1 a good marker for studying root meristem activity. PMID- 26821589 TI - Two-photon absorption of ligand-protected Ag15 nanoclusters. Towards a new class of nonlinear optics nanomaterials. AB - We report theoretical and experimental results on two-photon absorption (TPA) cross section of thiolated small silver cluster Ag15L11 exhibiting extraordinary large TPA in red. Our findings provide the responsible mechanism and allow proposing new classes of nanoclusters with large TPAs which are promising for biological and medical applications. PMID- 26821587 TI - Resilience measurement in later life: a systematic review and psychometric analysis. AB - OBJECTIVES: To systematically review and examine the psychometric properties of established resilience scales in older adults, i.e. >=60 years. METHODS: A systematic review of Scopus and Web of Science databases was undertaken using the search strategy "resilience" AND (ageing OR aging)". Independent title/abstract and fulltext screening were undertaken, identifying original peer-reviewed English articles that conducted psychometric validation studies of resilience metrics in samples aged >=60 years. Data on the reliability/validity of the included metrics were extracted from primary studies. RESULTS: Five thousand five hundred nine studies were identified by the database search, 426 used resilience psychometrics, and six psychometric analysis studies were included in the final analysis. These studies conducted analyses of the Connor Davidson Resilience Scale (CD-RISC) and its shortened 10-item version (CD-RISC10), the Resilience Scale (RS) and its shortened 5- (RS-5) and 11- (RS-11) item versions, and the Brief Resilient Coping Scale (BRCS). All scales demonstrated acceptable levels of internal consistency, convergent/discriminant validity and theoretical construct validity. Factor structures for the RS, RS-11 and CD-RISC diverged from the structures in the original studies. CONCLUSION: The RS, RS-5, RS-11, CD-RISC, CD RISC10 and BRCS demonstrate psychometric robustness adequate for continued use in older populations. However, results from the current study and pre-existing theoretical construct validity studies most strongly support the use of the RS, with modest and preliminary support for the CD-RISC and BRCS, respectively. Future studies assessing the validity of these metrics in older populations, particularly with respect to factor structure, would further strengthen the case for the use of these scales. PMID- 26821590 TI - Erratum to: Ventilator-associated pneumonia in the ICU. PMID- 26821588 TI - Understanding complexity in the HIF signaling pathway using systems biology and mathematical modeling. AB - Hypoxia is a common micro-environmental stress which is experienced by cells during a range of physiologic and pathophysiologic processes. The identification of the hypoxia-inducible factor (HIF) as the master regulator of the transcriptional response to hypoxia transformed our understanding of the mechanism underpinning the hypoxic response at the molecular level and identified HIF as a potentially important new therapeutic target. It has recently become clear that multiple levels of regulatory control exert influence on the HIF pathway giving the response a complex and dynamic activity profile. These include positive and negative feedback loops within the HIF pathway as well as multiple levels of crosstalk with other signaling pathways. The emerging model reflects a multi-level regulatory network that affects multiple aspects of the physiologic response to hypoxia including proliferation, apoptosis, and differentiation. Understanding the interplay between the molecular mechanisms involved in the dynamic regulation of the HIF pathway at a systems level is critically important in defining new appropriate therapeutic targets for human diseases including ischemia, cancer, and chronic inflammation. Here, we review our current knowledge of the regulatory circuits which exert influence over the HIF response and give examples of in silico model-based predictions of the dynamic behaviour of this system. PMID- 26821591 TI - Gaps between the subjective needs of older facility residents and how care workers understand them: a pairwise cross-sectional study. AB - BACKGROUND: To promote active daily living and improve the quality of life of older facility residents, it is important that care staff understand their day-to day activities and needs. However, only a few studies have examined the needs of older residents and how care workers understand them. This study aimed to examine the subjective needs of older residents at aged care facilities, care workers' understanding of these needs, and the gaps that exist between them. METHODS: Structured interviews with older residents with no severe cognitive impairment in ten Japanese aged care facilities and a questionnaire survey of care workers were conducted in 2008 regarding resident subjective needs. The questionnaire, which had satisfactory factorial validity, internal consistency, and reproducibility, consisted of seven items on basic activities of daily living (BADL), five items on instrumental ADL (IADL), eight items on environment and lifestyle (EL), and five items on emotion (EM). Pair-wise analyses were performed to compare responses. RESULTS: Responses of 115 pairs were analyzed (residents >=75 years, 85 %; 21 men, 94 women). Median proportions of residents with IADL (66 %) and EL (69 %) needs were lower compared with those with BADL (83 %) and EM (91 %) needs. Median proportions of care workers understanding IADL (55 %) and EL (60 %) needs were lower compared with those understanding BADL (87 %) and EM (87 %) needs. Less than half of the care workers understood IADL needs for household chores (30 %) and money management (43 %), and an EL need for playing a role (41 %). CONCLUSIONS: Gaps were found between resident subjective needs and how care workers understood them. Specifically, care workers underestimated older residents' IADL and EL needs, especially with regard to playing a role. These results highlight the need for care workers to set goals based on each resident's subjective needs and plan strategies for care provision accordingly. PMID- 26821592 TI - The impact of clinical, psychological, behavioral, social, and environmental factors on self-perceived symptom severity in a male cohort with intermittent claudication. AB - OBJECTIVE: To understand the relationship between self-perceived severity of intermittent claudication and various associated nonclinical factors, we examined how correlates in domains of physical activity (ie, clinical, psychological, behavioral, social, and environmental factors) relate to exertional limb symptoms. METHODS: A survey was administered to individuals with intermittent claudication during their initial outpatient assessment. The subjects' self reported exertional limb symptom severity and classic-versus-atypical claudication classification was based on the Walking Impairment Questionnaire (WIQ) and San Diego Claudication Questionnaire (SDCQ), respectively. We evaluated psychosocial and environmental factors, osteoarthritis symptoms, health, behaviors, and beliefs. Logistic and linear regressions identified factors with a strong independent association with total WIQ scores and the SDCQs. RESULTS: A cohort of 102 subjects (99.0% male) was enrolled in the study. The median age was 65 years with a median ankle-brachial index of 0.69. Forty-three subjects (43%) had "typical" claudication per SDCQs. Individuals with atypical claudication were more likely to report higher Aberdeen Clinical Back Pain Questionnaire scores (odds ratio, 1.04; P = .04) and no depressive symptoms (odds ratio, 8.30; P = .03). Exertional limb symptom severity among the entire cohort was significantly associated with increasing osteoarthritis symptoms (P <.001), age (P = .02), a reserved personality (P = .008), and the belief that an exercise regimen would not improve symptoms (P = .005), self-perceived levels of boredom (P = .002), and the belief that exercise (P = .002) was the best way to improve symptoms were associated with decreased symptom severity. When restricted to those with atypical pain, significant factors associated with increasing exertional symptom severity included age greater than 60 years (P = .005), osteoarthritis (P = .02), alcohol use (P = .01), belief that exercise would not improve walking (P = .03), and difficulty walking around the neighborhood (P = .02). When restricted to those with classic claudication, significant factors associated with increasing exertional limb symptom severity included frequent pain or aching in the calves while walking or sitting (P = .03 [walking]; P = .01 [sitting]) and occasional morning joint stiffness (P = .007). Exertional limb symptom severity was also associated with high limitations at home (P = .003) and a belief that exercise would not improve walking (P = .005) among those with classic claudication. CONCLUSIONS: Symptom severity and type of pain are associated with a number of nonclinical factors. A multidomain approach, as indicated by the models above, would benefit the continuum of care for intermittent claudication, where management is integrated and coordinated among multiple lines of care. PMID- 26821593 TI - Molecular cytogenetic analysis of dicentric chromosomes in acute myeloid leukemia. AB - Dicentric chromosomes (DCs) have been described in many hematological diseases, including acute myeloid leukemia (AML). They are markers of cancer and induce chromosomal instability, leading to the formation of other chromosomal aberrations and the clonal evolution of pathological cells. Our knowledge of the roles and behavior of human DCs is often derived from studies of induced DCs and cell lines. It is difficult to identify all the DCs in the karyotypes of patients because of the limitations of metaphase cytogenetic methods. The aim of this study was to revise the karyotypes of 20 AML patients in whom DCs were found with conventional G-banding or multicolor fluorescence in situ hybridization (mFISH) with (multi)centromeric probes and to characterize the DCs at the molecular cytogenetic level. FISH analyses confirmed 23 of the 29 expected DCs in 18 of 20 patients and identified 13 others that had not been detected cytogenetically. Fourteen DCs were altered by other chromosomal changes. In conclusion, karyotypes with DCs are usually very complex, and we have shown that they often contain more than one DC, which can be missed with conventional or mFISH methods. Our study indicates an association between number of DCs in karyotype and very short survival of patients. PMID- 26821595 TI - Layering of ionic liquids on rough surfaces. AB - Understanding the behavior of ionic liquids (ILs) either confined between rough surfaces or in rough nanoscale pores is of great relevance to extend studies performed on ideally flat surfaces to real applications. In this work we have performed an extensive investigation of the structural forces between two surfaces with well-defined roughness (<9 nm RMS) in 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide by atomic force microscopy. Statistical studies of the measured layer thicknesses, layering force, and layering frequency reveal the ordered structure of the rough IL-solid interface. Our work shows that the equilibrium structure of the interfacial IL strongly depends on the topography of the contact. PMID- 26821594 TI - Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials. AB - AIMS: The aim of this study was to assess the net clinical and prognostic effects of intravenous (i.v.) iron therapy in patients with systolic heart failure (HF) and iron deficiency (ID). METHODS AND RESULTS: We performed an aggregate data meta-analysis (random effects model) of randomized controlled trials that evaluated the effects of i.v. iron therapy in iron-deficient patients with systolic HF. We searched electronic databases up to September 2014. We identified five trials which fulfilled the inclusion criteria (509 patients received i.v. iron therapy in comparison with 342 controls). Intravenous iron therapy has been shown to reduce the risk of the combined endpoint of all-cause death or cardiovascular hospitalization [odds ratio (OR) 0.44, 95% confidence interval (CI) 0.30-0.64, P < 0.0001], and the combined endpoint of cardiovascular death or hospitalization for worsening HF (OR 0.39, 95% CI 0.24-0.63, P = 0.0001). Intravenous iron therapy resulted in a reduction in NYHA class (data are reported as a mean net effect with 95% CIs for all continuous variables) (-0.54 class, 95% CI -0.87 to -0.21, P = 0.001); an increase in 6-min walking test distance (+31 m, 95% CI 18-43, P < 0.0001); and an improvement in quality of life [Kansas City Cardiomyopathy Questionnaire (KCCQ) score +5.5 points, 95% CI 2.8-8.3, P < 0.0001; European Quality of Life-5 Dimensions (EQ-5D) score +4.1 points, 95% CI 0.8-7.3, P = 0.01; Minnesota Living With Heart Failure Questionnaire (MLHFQ) score -19 points, 95% CI:-23 to -16, P < 0.0001; and Patient Global Assessment (PGA) +0.70 points, 95% CI 0.31-1.09, P = 0004]. CONCLUSION: The evidence indicates that i.v. iron therapy in iron-deficient patients with systolic HF improves outcomes, exercise capacity, and quality of life, and alleviates HF symptoms. PMID- 26821596 TI - It felt fluent but I did not like it: fluency effects in faces versus patterns. AB - Whether you like a person or not is often appraised in a glance. However, under such short presentation durations stimuli are harder to perceive and, according to hedonic fluency theory-which holds that higher fluency is linked to higher liking-thus, are liked less. Given that liking considerably influences person perception, we tested how shorter and longer presentation durations affect liking for faces and compared this with abstract patterns. To capture facets of fluency of processing we assessed felt fluency, liking, and certainty ratings. Following predictions of fluency theory, longer presentation durations led to higher felt fluency, certainty, and positively affected liking judgments in the abstract patterns. In faces, felt fluency and certainty also increased with longer durations. However, with longer durations, faces were liked less, and liking was not related to felt fluency. In other words, in contrast to hedonic fluency theory, faces are more attractive when only seen for a short amount of time. Thus, fluency does not inevitably lead to more positive evaluations-it rather depends on the stimulus category. We discuss these findings in terms of the special status that faces have with regard to human perception and evaluation. PMID- 26821598 TI - Real-time quantitation of internal metabolic activity of three-dimensional engineered tissues using an oxygen microelectrode and optical coherence tomography. AB - Recent progress in tissue engineering technology has enabled us to develop thick tissue constructs that can then be transplanted in regenerative therapies. In clinical situations, it is vital that the engineered tissues to be implanted are safe and functional before use. However, there is currently a limited number of studies on real-time quality evaluation of thick living tissue constructs. Here we developed a system for quantifying the internal activities of engineered tissues, from which we can evaluate its quality in real-time. The evaluation was achieved by measuring oxygen concentration profiles made along the vertical axis and the thickness of the tissues estimated from cross-sectional images obtained noninvasively by an optical coherence tomography system. Using our novel system, we obtained (i) oxygen concentration just above the tissues, (ii) gradient of oxygen along vertical axis formed above the tissues within culture medium, and (iii) gradient of oxygen formed within the tissues in real-time. Investigating whether these three parameters could be used to evaluate engineered tissues during culturing, we found that only the third parameter was a good candidate. This implies that the activity of living engineered tissues can be monitored in real-time by measuring the oxygen gradient within the tissues. The proposed measuring strategy can be applied to developing more efficient culturing methods to support the fabrication of engineered thick tissues, as well as providing methods to confirm the quality in real-time. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 855-864, 2017. PMID- 26821597 TI - Very-low and low-density lipoproteins induce neutral lipid accumulation and impair migration in monocyte subsets. AB - Blood monocytes are heterogeneous effector cells of the innate immune system. In circulation these cells are constantly in contact with lipid-rich lipoproteins, yet this interaction is poorly characterised. Our aim was to examine the functional effect of hyperlipidaemia on blood monocytes. In the Ldlr(-/-) mouse monocytes rapidly accumulate cytoplasmic neutral lipid vesicles during hyperlipidaemia. Functional analysis in vivo revealed impaired monocyte chemotaxis towards peritonitis following high fat diet due to retention of monocytes in the greater omentum. In vitro assays using human monocytes confirmed neutral lipid vesicle accumulation after exposure to LDL or VLDL. Neutral lipid accumulation did not inhibit phagocytosis, endothelial adhesion, intravascular crawling and transmigration. However, lipid loading led to a migratory defect towards C5a and disruption of cytoskeletal rearrangement, including an inhibition of RHOA signaling. These data demonstrate distinct effects of hyperlipidaemia on the chemotaxis and cytoskeletal regulation of monocyte subpopulations. These data emphasise the functional consequences of blood monocyte lipid accumulation and reveal important implications for treating inflammation, infection and atherosclerosis in the context of dyslipidaemia. PMID- 26821599 TI - Energy recovery from organic fractions of municipal solid waste: A case study of Hyderabad city, Pakistan. AB - Non-renewable energy sources have remained the choice of the world for centuries. Rapid growth in population and industrialisation have caused their shortage and environmental degradation by using them. Thus, at the present rate of consumption, they will not last very long. In this prospective, this study has been conducted. The estimation of energy in terms of biogas and heat from various organic fractions of municipal solid waste is presented and discussed. The results show that organic fractions of municipal solid waste possess methane potential in the range of 3%-22% and their heat capacity ranges from 3007 to 20,099 kJ kg(-1) Also, theoretical biogas potential of different individual fruit as well as vegetable components and mixed food waste are analysed and estimated in the range of 608-1244 m(3) t(-1) Further, the share of bioenergy from municipal solid waste in the total primary energy supply in Pakistan has been estimated to be 1.82%. About 8.43% of present energy demand of the country could be met from municipal solid waste. The study leads us to the conclusion that the share of imported energy (i.e. 0.1% of total energy supply) and reduction in the amount of energy from fossil fuels can be achieved by adopting a waste-to-energy system in the country. PMID- 26821600 TI - Rapid Determination of Fast Protein Dynamics from NMR Chemical Exchange Saturation Transfer Data. AB - Functional motions of (15)N-labeled proteins can be monitored by solution NMR spin relaxation experiments over a broad range of timescales. These experiments however typically take of the order of several days to a week per protein. Recently, NMR chemical exchange saturation transfer (CEST) experiments have emerged to probe slow millisecond motions complementing R1rho and CPMG-type experiments. CEST also simultaneously reports on site-specific R1 and R2 parameters. It is shown here how CEST-derived R1 and R2 relaxation parameters can be measured within a few hours at an accuracy comparable to traditional relaxation experiments. Using a "lean" version of the model-free approach S(2) order parameters can be determined that match those from the standard model-free approach applied to (15)N R1, R2 , and {(1)H}-(15)N NOE data. The new methodology, which is demonstrated for ubiquitin and arginine kinase (42 kDa), should serve as an effective screening tool of protein dynamics from picosecond to-millisecond timescales. PMID- 26821601 TI - Prophylactic laser photocoagulation of fundal coloboma: does it really help? PMID- 26821602 TI - Multicolour photochromism of colloidal solutions of niobate nanosheets intercalated with several kinds of metal ions. AB - Colourless and transparent colloidal solutions of niobate nanosheets intercalated with some kinds of metal ions (M-NNS, M: metal) showed quasi-reversible photochromism. Ultraviolet light irradiation of the solutions induced a change in color while maintaining the transparency, and the color change was dependent on the metal ions. The coloured solutions were bleached by exposure to an oxidizing atmosphere. This cycle could be repeated several times. PMID- 26821603 TI - The prevalence and distribution of the atherosclerotic plaques in the abdominal aorta and its branches. AB - BACKGROUND: The aim of our study was to determine the existence, distribution, type and burden of the atherosclerotic plaques which are found in the abdominal aorta, its branches and the branching points. MATERIALS AND METHODS: Two hundred and sixty-one patients (117 female, 144 male; mean age 53.34 +/- 16.02, range 12 84) who underwent dual-source computed tomography angiography (CTA) were retrospectively analysed. The prevalence and distribution of the plaques in the proximal, middle and distal parts of abdominal aorta and its branches; coeliac trunk, superior and inferior mesenteric arteries, renal arteries, splenic artery and common, external and internal iliac arteries and in the aortic orifices, the type and severity of these plaques and their relations with age and gender were studied. RESULTS: In our study, 69.3% of the patients had atherosclerotic plaques, mostly at the distal part of abdominal aorta. The existence of the plaques increased with age. The types of these plaques were mixed (43%), calcified (24%) and soft (3%). Mixed and calcified plaques were more common in the abdominal aorta and its branches, respectively. All of the arteries except for inferior mesenteric artery mostly had mild plaques. The plaques at the branching points, which were most frequently localised in the aortic bifurcation, were found in the 41.8% of the patients. The plaques in the branches were usually accompanied by atherosclerosis of abdominal aorta. CONCLUSIONS: Dual-source CTA enables mapping of atherosclerotic burden in abdominal arteries. Knowing the localisation, type and severity of the atherosclerotic plaques can be important to predict the clinical results and choose the proper treatment. PMID- 26821605 TI - Hollow Zn/Co Zeolitic Imidazolate Framework (ZIF) and Yolk-Shell Metal@Zn/Co ZIF Nanostructures. AB - Metal-organic frameworks (MOFs) feature a great possibility for a broad spectrum of applications. Hollow MOF structures with tunable porosity and multifunctionality at the nanoscale with beneficial properties are desired as hosts for catalytically active species. Herein, we demonstrate the formation of well-defined hollow Zn/Co-based zeolitic imidazolate frameworks (ZIFs) by use of epitaxial growth of Zn-MOF (ZIF-8) on preformed Co-MOF (ZIF-67) nanocrystals that involve in situ self-sacrifice/excavation of the Co-MOF. Moreover, any type of metal nanoparticles can be accommodated in Zn/Co-ZIF shells to generate yolk shell metal@ZIF structures. Transmission electron microscopy and tomography studies revealed the inclusion of these nanoparticles within hollow Zn/Co-ZIF with dominance of the Zn-MOF as shell. Our findings lead to a generalization of such hollow systems that are working effectively to other types of ZIFs. PMID- 26821604 TI - Large-Area Growth of Turbostratic Graphene on Ni(111) via Physical Vapor Deposition. AB - Single-layer graphene has demonstrated remarkable electronic properties that are strongly influenced by interfacial bonding and break down for the lowest energy configuration of stacked graphene layers (AB Bernal). Multilayer graphene with relative rotations between carbon layers, known as turbostratic graphene, can effectively decouple the electronic states of adjacent layers, preserving properties similar to that of SLG. While the growth of AB Bernal graphene through chemical vapor deposition has been widely reported, we investigate the growth of turbostratic graphene on heteroepitaxial Ni(111) thin films utilizing physical vapor deposition. By varying the carbon deposition temperature between 800 -1100 degrees C, we report an increase in the graphene quality concomitant with a transition in the size of uniform thickness graphene, ranging from nanocrystallites to thousands of square microns. Combination Raman modes of as grown graphene within the frequency range of 1650 cm(-1) to 2300 cm(-1), along with features of the Raman 2D mode, were employed as signatures of turbostratic graphene. Bilayer and multilayer graphene were directly identified from areas that exhibited Raman characteristics of turbostratic graphene using high resolution TEM imaging. Raman maps of the pertinent modes reveal large regions of turbostratic graphene on Ni(111) thin films at a deposition temperature of 1100 degrees C. PMID- 26821606 TI - Quercetin and vitamin E attenuate Bonny Light crude oil-induced alterations in testicular apoptosis, stress proteins and steroidogenic acute regulatory protein in Wistar rats. AB - Studies have shown the reproductive effects of Bonny Light crude oil (BLCO) via the mechanism of oxidative stress and testicular apoptosis. We investigated the protective role of quercetin and vitamin E on BLCO-induced testicular apoptosis. Experimental rats were divided into four groups of four each. Animals were orally administered 2 ml/kg corn oil (control: group 1), BLCO-800 mg/kg body weight + 10 mg/kg quercetin (group 2), BLCO-800 mg/kg body weight + 50 mg/kg vitamin E (group 3) and BLCO-800 mg/kg body weight only (group 4) for 7 d. Protein levels of caspase 3, FasL, NF-kB, steroidogenic acute regulatory protein and stress response proteins were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunofluorescence staining was used to quantify the expression of caspase 3, FasL and NF-kB. Apoptosis was quantified by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Administration of BLCO resulted in a significant increase in the levels of stress response proteins and apoptosis-related proteins by 50% and above after 7 d following BLCO exposure and a concomitant increase in expression of caspase 3, FasL and NF-kB expression by immunofluorescence staining. Apoptosis showed a significant increase in TUNEL positive cells. Co-administration with quercetin or vitamin E reversed BLCO-induced apoptosis and levels of stress protein, relative to control. These findings suggest that quercetin and vitamin E may confer protection against BLCO-induced testicular oxidative stress-related apoptosis. PMID- 26821607 TI - Impact of Bacterial-Fungal Interactions on the Colonization of the Endosphere. AB - Research on different endophyte taxa and the related scientific disciplines have largely developed separately, and comprehensive community-level studies on bacterial and fungal interactions and their importance are lacking. Here, we discuss the transmission modes of bacteria and fungi and the nature of their interactions in the endosphere at both the molecular and physiological level. Mixed-community biofilms in the endosphere may have a role in protecting endophytes against encountered stresses, such as from plant defense systems. However, transmission from static (in biofilms) to free-living (planktonic) forms may be crucial for the exploration of new habitable spaces in plants. Important features previously recognized as plant-microbe interactions or antagonism in endophyte genomes and metagenomes are proposed to have essential roles in the modulation of endophyte communities. PMID- 26821609 TI - Gas permeation through nanoporous membranes in the transitional flow region. AB - An experimental study on the permeability of anodic alumina (20-120 nm) and track etched (30 nm) nanoporous membranes for different gases in the transitional flow regime is reported in the range of Knudsen numbers from 0.1 to 10. A significant variation (up to 30%) of the membrane permeance for different gases at the same Knudsen numbers is reported with certainty. It is established that this discrepancy relates to a molecule's effective collision area, which is poorly described in the frameworks of conventional gas permeation models. Two models are proposed for the description of the effect: self-diffusion of penetrate gases due to intermolecular collisions and enhancement of the slip flow contribution due to tangential momentum accommodation growth with the decrease of a molecule's effective collision area. The best fit parameters for the simultaneous fit of the experimental data with different models for 30 membrane-gas pairs are given. PMID- 26821608 TI - Preferential interaction of the Alzheimer peptide Abeta-(1-42) with Omega-3 containing lipid bilayers: structure and interaction studies. AB - Many age-related neurodegenerative diseases, including Alzheimer Disease (AD), are elicited by an interplay of genetic, environmental, and dietary factors. Food rich in Omega-3 phospholipids seems to reduce the AD incidence. To investigate the molecular basis of this beneficial effect, we have investigated by CD and ESR studies the interaction between the Alzheimer peptide Abeta-(1-42) and biomimetic lipid bilayers. The inclusion of 1,2-didocosahexaenoyl-sn-glycero-3 phosphocholine does not change significantly the bilayers organization, but favors its Abeta-(1-42) interaction. The Omega-3 lipid amount modulates the effect intensity, suggesting a peptide selectivity for membranes containing polyunsatured fatty acids (PUFA) and providing hints for the mechanism and therapy of AD. PMID- 26821610 TI - Expression of cell adhesion molecule CD44 in mucoepidermoid carcinoma and its association with the tumor behavior. AB - BACKGROUND: The most common malignant salivary gland tumors that affect both adult and children is mucoepidermoid carcinoma. It usually affects both minor and major salivary glands but parotid gland is considering the most common site in which this tumor arises. CD44, a trans-membrane glycoprotein, is an adhesion molecule of cell surface that play a role in the connections between cell-cell and cell-matrix. Many malignant tumors express high levels of CD44, thus, CD44 may be used as an indicator of aggressive behavior of some human malignancy. We evaluate CD44 expression in different grades of mucoepidermoid carcinoma and determine whether expression of CD44 can be used to predict tumor aggressiveness. METHODS: Fifteen cases of mucoepidermoid carcinoma were retrieved from the oral pathology archives and grouped according to the histological grade as well as the clinical behavior regarding metastases and/or recurrence. Tissue sections were immunohistochemically stained for CD44. CD44 staining was scored for intensity and proportion of cells stained. RESULTS: A higher proportion of high-grade tumor tissues showed moderate or strong CD44 staining compared to low-grade tumors. Additionally, CD44 expression was stronger in tumors from patients with recurrences or metastases, but theses differences were not statistically significant. CONCLUSION: Our result showed that mucoepidermoid carcinomas are immunohistochemistry positive to CD44 compare to normal. A trend of CD44 expression associated with different histological grading and aggressive behavior of this tumor. PMID- 26821611 TI - A Sugar-Based Gelator for Marine Oil-Spill Recovery. AB - Marine oil spills constitute an environmental disaster with severe adverse effects on the economy and ecosystem. Phase-selective organogelators (PSOGs), molecules that can congeal oil selectively from oil-water mixtures, have been proposed to be useful for oil-spill recovery. However, a major drawback lies in the mode of application of the PSOG to an oil spill spread over a large area. The proposed method of using carrier solvents is impractical for various reasons. Direct application of the PSOG as a solid, although it would be ideal, is unknown, presumably owing to poor dispersion of the solid through the oil. We have designed five cheap and easy-to-make glucose-derived PSOGs that disperse in the oil phase uniformly when applied as a fine powder. These gelators were shown to selectively congeal many oils, including crude oil, from oil-water mixtures to form stable gels, which is an essential property for efficient oil-spill recovery. We have demonstrated that these PSOGs can be applied aerially as a solid powder onto a mixture of crude oil and sea water and the congealed oil can then be scooped out. Our innovative mode of application and low cost of the PSOG offers a practical solution to oil-spill recovery. PMID- 26821612 TI - Chemoenzymatic Route for the Synthesis of (S)-Moprolol, a Potential beta-Blocker. AB - A biocatalytic route for the synthesis of a potential beta-blocker, (S)-moprolol is reported here. Enantiopure synthesis of moprolol is mainly dependent on the chiral intermediate, 3-(2-methoxyphenoxy)-propane-1,2-diol. Various commercial lipases were screened for the enantioselective resolution of (RS)-3-(2 methoxyphenoxy)propane-1,2-diol to produce the desired enantiomer. Among them, Aspergillus niger lipase (ANL) was selected on the basis of both stereo- and regioselectivity. The optimized values of various reaction parameters were determined such as enzyme (15 mg/mL), substrate concentration (10 mM), organic solvent (toluene), reaction temperature (30 degrees C), and time (18 h).The optimized conditions led to achieving >49% yield with high enantiomeric excess of (S)-3-(2-methoxyphenoxy)propane-1,2-diol. The lipase-mediated catalysis showed regioselective acylation with dual stereoselectivity. Further, the enantiopure intermediate was used for the synthesis of (S)-moprolol, which afforded the desired beta-blocker. PMID- 26821613 TI - A Triatomic Silicon(0) Cluster Stabilized by a Cyclic Alkyl(amino) Carbene. AB - Reduction of the neutral carbene tetrachlorosilane adduct (cAAC)SiCl4 (cAAC=cyclic alkyl(amino) carbene :C(CMe2)2 (CH2)N(2,6-iPr2C6H3) with potassium graphite produces stable (cAAC)3Si3, a carbene-stabilized triatomic silicon(0) molecule. The Si-Si bond lengths in (cAAC)3Si3 are 2.399(8), 2.369(8) and 2.398(8) A, which are in the range of Si-Si single bonds. Each trigonal pyramidal silicon atom of the triangular molecule (cAAC)3Si3 possesses a lone pair of electrons. Its bonding, stability, and electron density distributions were studied by quantum chemical calculations. PMID- 26821614 TI - Enhanced film thickness for Neel wall in soft magnetic film by introducing strong magnetocrystalline anisotropy. AB - This study investigated the magnetic domain walls in a single-layer soft magnetic film with strong magnetocrystalline anisotropy energy. The soft magnetic film is composed of a highly c-axis-oriented hcp-Co81Ir19 alloy with strong negative magnetocrystalline anisotropy. The domain structure of the soft Co81Ir19 films with thickness ranging from 50-230 nm in a demagnetization state was observed through magnetic force microscopy and Lorentz transmission electron microscopy. Results reveal that the critical transition thickness at which the domain wall changes from Neel type to Bloch type is about 138 nm, which is much larger than the critical value of traditional Fe- and Co-based soft magnetic films with negligible magnetocrystalline anisotropy. Theoretical calculation was also performed and the calculated result agrees well with experimental data. PMID- 26821615 TI - A log-rank-type test to compare net survival distributions. AB - In population-based cancer studies, it is often interesting to compare cancer survival between different populations. However, in such studies, the exact causes of death are often unavailable or unreliable. Net survival methods were developed to overcome this difficulty. Net survival is the survival that would be observed if the disease under study was the only possible cause of death. The Pohar-Perme estimator (PPE) is a nonparametric consistent estimator of net survival. In this article, we present a log-rank-type test for comparing net survival functions (as estimated by PPE) between several groups. We put the test within the counting process framework to introduce the inverse probability weighting procedure as required by the PPE. We built a stratified version to control for categorical covariates that affect the outcome. We performed simulation studies to evaluate the performance of this test and worked an application on real data. PMID- 26821616 TI - Expression of Concern: The polarity factor Bucky ball associates with the centrosome and promotes microtubule rearrangements to establish the oocyte axis in zebrafish by Forbes et al. Development doi: 10.1242/dev.129023. PMID- 26821617 TI - Stochastic neutral modelling of the Gut Microbiota's relative species abundance from next generation sequencing data. AB - BACKGROUND: Interest in understanding the mechanisms that lead to a particular composition of the Gut Microbiota is highly increasing, due to the relationship between this ecosystem and the host health state. Particularly relevant is the study of the Relative Species Abundance (RSA) distribution, that is a component of biodiversity and measures the number of species having a given number of individuals. It is the universal behaviour of RSA that induced many ecologists to look for theoretical explanations. In particular, a simple stochastic neutral model was proposed by Volkov et al. relying on population dynamics and was proved to fit the coral-reefs and rain forests RSA. Our aim is to ascertain if this model also describes the Microbiota RSA and if it can help in explaining the Microbiota plasticity. RESULTS: We analyzed 16S rRNA sequencing data sampled from the Microbiota of three different animal species by Jeraldo et al. Through a clustering procedure (UCLUST), we built the Operational Taxonomic Units. These correspond to bacterial species considered at a given phylogenetic level defined by the similarity threshold used in the clustering procedure. The RSAs, plotted in the form of Preston plot, were fitted with Volkov's model. The model fits well the Microbiota RSA, except in the tail region, that shows a deviation from the neutrality assumption. Looking at the model parameters we were able to discriminate between different animal species, giving also a biological explanation. Moreover, the biodiversity estimator obtained by Volkov's model also differentiates the animal species and is in good agreement with the first and second order Hill's numbers, that are common evenness indexes simply based on the fraction of individuals per species. CONCLUSIONS: We conclude that the neutrality assumption is a good approximation for the Microbiota dynamics and the observation that Volkov's model works for this ecosystem is a further proof of the RSA universality. Moreover, the ability to separate different animals with the model parameters and biodiversity number are promising results if we think about future applications on human data, in which the Microbiota composition and biodiversity are in close relationships with a variety of diseases and life styles. PMID- 26821619 TI - The duality principle in the presence of postselection. AB - The duality principle, a cornerstone of quantum mechanics, limits the coexistence of wave and particle behaviours of quantum systems. This limitation takes a quantitative form when applied to the visibility of interference fringes and predictability of paths within a two-alternative system, which are bound by the inequality . However, if such a system is coupled to its environment, it becomes possible to obtain conditional measures of visibility and predictability, i.e. measures that are conditioned on the state of the environment. We show that in this case, the predictability and visibility values can lead to an apparent violation of the duality principle. We experimentally realize this apparent violation in a controlled manner by enforcing a fair-sampling-like loophole via postselection. This work highlights some of the subtleties that one can encounter while interpreting familiar quantities such as which-alternative information and visibility. While we concentrated on an extreme example, it is of utmost importance to realise that such subtleties might also be present in cases where the results are not obviously violating an algebraic bound, making them harder (but not any less crucial) to detect. PMID- 26821618 TI - Comparative genome-wide analysis and evolutionary history of haemoglobin processing and haem detoxification enzymes in malarial parasites. AB - BACKGROUND: Malaria parasites have evolved a series of intricate mechanisms to survive and propagate within host red blood cells. Intra-erythrocytic parasitism requires these organisms to digest haemoglobin and detoxify iron-bound haem. These tasks are executed by haemoglobin-specific proteases and haem biocrystallization factors that are components of a large multi-subunit complex. Since haemoglobin processing machineries are functionally and genetically linked to the modes of action and resistance mechanisms of several anti-malarial drugs, an understanding of their evolutionary history is important for drug development and drug resistance prevention. METHODS: Maximum likelihood trees of genetic repertoires encoding haemoglobin processing machineries within Plasmodium species, and with the representatives of Apicomplexan species with various host tropisms, were created. Genetic variants were mapped onto existing three dimensional structures. Genome-wide single nucleotide polymorphism data were used to analyse the selective pressure and the effect of these mutations at the structural level. RESULTS: Recent expansions in the falcipain and plasmepsin repertoires are unique to human malaria parasites especially in the Plasmodium falciparum and P. reichenowi lineage. Expansion of haemoglobin-specific plasmepsins occurred after the separation event of Plasmodium species, but the other members of the plasmepsin family were evolutionarily conserved with one copy for each sub-group in every Apicomplexan species. Haemoglobin-specific falcipains are separated from invasion-related falcipain, and their expansions within one specific locus arose independently in both P. falciparum and P. vivax lineages. Gene conversion between P. falciparum falcipain 2A and 2B was observed in artemisinin-resistant strains. Comparison between the numbers of non synonymous and synonymous mutations suggests a strong selective pressure at falcipain and plasmepsin genes. The locations of amino acid changes from non synonymous mutations mapped onto protein structures revealed clusters of amino acid residues in close proximity or near the active sites of proteases. CONCLUSION: A high degree of polymorphism at the haemoglobin processing genes implicates an imposition of selective pressure. The identification in recent years of functional redundancy of haemoglobin-specific proteases makes them less appealing as potential drug targets, but their expansions, especially in the human malaria parasite lineages, unequivocally point toward their functional significance during the independent and repetitive adaptation events in malaria parasite evolutionary history. PMID- 26821620 TI - The role of cranial and thoracic electromyography within diagnostic criteria for amyotrophic lateral sclerosis. AB - INTRODUCTION: The contribution of cranial and thoracic region electromyography (EMG) to diagnostic criteria for amyotrophic lateral sclerosis (ALS) has not been evaluated. METHODS: Clinical and EMG data from each craniospinal region were retrospectively assessed in 470 patients; 214 had ALS. Changes to diagnostic classification in Awaji-Shima and revised El Escorial criteria after withdrawal of cranial/thoracic EMG data were ascertained. RESULTS: Sensitivity for lower motor neuron involvement in ALS was highest in the cervical/lumbar regions; specificity was highest in cranial/thoracic regions. Cranial EMG contributed to definite/probable Awaji-Shima categorization in 1.4% of patients. Thoracic EMG made no contribution. For revised El Escorial criteria, cranial and thoracic data reclassified 1% and 5% of patients, respectively. CONCLUSION: Cranial EMG data make small contributions to both criteria, whereas thoracic data contribute only to the revised El Escorial criteria. However, cranial and thoracic region abnormalities are specific in ALS. Consideration should be given to allowing greater diagnostic contribution from thoracic EMG. Muscle Nerve 54: 378-385, 2016. PMID- 26821621 TI - Reduction in Total Cardiovascular Events With Ezetimibe/Simvastatin Post-Acute Coronary Syndrome: The IMPROVE-IT Trial. AB - BACKGROUND: Intensive low-density lipoprotein cholesterol therapy with ezetimibe/simvastatin in IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) significantly reduced the first primary endpoint (PEP) in patients post-acute coronary syndrome (ACS) compared to placebo/simvastatin. OBJECTIVES: This analysis tested the hypothesis that total events, including those beyond the first event, would also be reduced with ezetimibe/simvastatin therapy. METHODS: All PEP events (cardiovascular [CV] death, myocardial infarction [MI], stroke, unstable angina [UA] leading to hospitalization, coronary revascularization >=30 days post-randomization) during a median 6-year follow-up were analyzed in patients randomized to receive ezetimibe/simvastatin or placebo/simvastatin in IMPROVE-IT. Negative binomial regression was used for the primary analysis. RESULTS: Among 18,144 patients, there were 9,545 total PEP events (56% were first events and 44% subsequent events). Total PEP events were significantly reduced by 9% with ezetimibe/simvastatin vs placebo/simvastatin (incidence-rate ratio [RR]: 0.91; 95% confidence interval [CI]: 0.85 to 0.97; p = 0.007), as were the 3 pre specified secondary composite endpoints and the exploratory composite endpoint of CV death, MI, or stroke (RR: 0.88; 95% CI: 0.81 to 0.96; p = 0.002). The reduction in total events was driven by decreases in total nonfatal MI (RR: 0.87; 95% CI: 0.79 to 0.96; p = 0.004) and total NF stroke (RR: 0.77; 95% CI: 0.65 to 0.93; p = 0.005). CONCLUSIONS: Lipid-lowering therapy with ezetimibe plus simvastatin improved clinical outcomes. Reductions in total PEP events, driven by reductions in MI and stroke, more than doubled the number of events prevented compared with examining only the first event. These data support continuation of intensive combination lipid-lowering therapy after an initial CV event. (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878). PMID- 26821622 TI - PROVE-IT to IMPROVE-IT: Why LDL-C Goals Still Matter in Post-ACS Patients. PMID- 26821623 TI - Cyclosporine A in Reperfused Myocardial Infarction: The Multicenter, Controlled, Open-Label CYCLE Trial. AB - BACKGROUND: Whether cyclosporine A (CsA) has beneficial effects in reperfused myocardial infarction (MI) is debated. OBJECTIVES: This study investigated whether CsA improved ST-segment resolution in a randomized, multicenter phase II study. METHODS: The authors randomly assigned 410 patients from 31 cardiac care units, age 63 +/- 12 years, with large ST-segment elevation MI within 6 h of symptom onset, Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 to 1 in the infarct-related artery, and committed to primary percutaneous coronary intervention, to 2.5 mg/kg intravenous CsA (n = 207) or control (n = 203) groups. The primary endpoint was incidence of >=70% ST-segment resolution 60 min after TIMI flow grade 3. Secondary endpoints included high-sensitivity cardiac troponin T (hs-cTnT) on day 4, left ventricular (LV) remodeling, and clinical events at 6 month follow-up. RESULTS: Time from symptom onset to first antegrade flow was 180 +/- 67 min; a median of 5 electrocardiography leads showed ST-segment deviation (quartile [Q]1 to Q3: 4 to 6); 49.8% of MIs were anterior. ST-segment resolution >=70% was found in 52.0% of CsA patients and 49.0% of controls (p = 0.55). Median hs-cTnT on day 4 was 2,160 (Q1 to Q3: 1,087 to 3,274) ng/l in CsA and 2,068 (1,117 to 3,690) ng/l in controls (p = 0.85). The 2 groups did not differ in LV ejection fraction on day 4 and at 6 months. Infarct site did not influence CsA efficacy. There were no acute allergic reactions or nonsignificant excesses of 6 month mortality (5.7% CsA vs. 3.2% controls, p = 0.17) or cardiogenic shock (2.4% CsA vs. 1.5% controls, p = 0.33). CONCLUSIONS: In the CYCLE (CYCLosporinE A in Reperfused Acute Myocardial Infarction) trial, a single intravenous CsA bolus just before primary percutaneous coronary intervention had no effect on ST segment resolution or hs-cTnT, and did not improve clinical outcomes or LV remodeling up to 6 months. (CYCLosporinE A in Reperfused Acute Myocardial Infarction [CYCLE]; NCT01650662; EudraCT number 2011-002876-18). PMID- 26821624 TI - Cyclosporine A Prior to Primary PCI in STEMI Patients: The Coup de Grace to Post Conditioning? PMID- 26821625 TI - Efficacy of Low-Dose Chlorthalidone and Hydrochlorothiazide as Assessed by 24-h Ambulatory Blood Pressure Monitoring. AB - BACKGROUND: Thiazide and thiazide-like diuretic agents are being increasingly used at lower doses. Hydrochlorothiazide (HCTZ) in the 12.5-mg dose remains the most commonly prescribed antihypertensive agent in the United States. OBJECTIVES: This study compared chlorthalidone, 6.25 mg daily, with HCTZ, 12.5 mg daily, by 24-h ambulatory blood pressure (ABP) monitoring and evaluated efficacy. Because HCTZ has been perceived as a short-acting drug, a third comparison with an extended-release formulation (HCTZ-controlled release [CR]) was added. METHODS: This 12-week comparative, double-blind, outpatient study randomized 54 patients with stage 1 hypertension to receive either chlorthalidone, 6.25 mg, (n = 16); HCTZ 12.5 mg (n = 18); or HCTZ-CR 12.5 mg (n = 20). ABP monitoring was performed at baseline and after 4 and 12 weeks of therapy. RESULTS: All 3 treatments significantly (p < 0.01) lowered office BP at weeks 4 and 12 from baseline. At weeks 4 and 12, significant reductions in systolic and diastolic 24-h ambulatory and nighttime BP (p < 0.01) were observed with chlorthalidone but not with HCTZ. At weeks 4 (p = 0.015) and 12 (p = 0.020), nighttime systolic ABP was significantly lower in the chlorthalidone group than in the the HCTZ group. With HCTZ therapy, sustained hypertension was converted into masked hypertension. In contrast to the HCTZ group, the HCTZ-CR group also showed a significant (p < 0.01) reduction in 24-h ABP. All 3 treatments were generally safe and well tolerated. CONCLUSIONS: Treatment with low-dose chlorthalidone, 6.25 mg daily, significantly reduced mean 24-h ABP as well as daytime and nighttime BP. Due to its short duration of action, no significant 24-h ABP reduction was seen with HCTZ, 12.5 mg daily, which merely converted sustained hypertension into masked hypertension. Thus, low-dose chlorthalidone, 6.25 mg, could be used as monotherapy for treatment of essential hypertension, whereas low-dose HCTZ monotherapy is not an appropriate antihypertensive drug. (Comparative Evaluation of Safety and Efficacy of Hydrochlorothiazide CR with Hydrochlorothiazide and Chlorthalidone in Patients With Stage I Essential Hypertension; CTRI/2013/07/003793). PMID- 26821626 TI - Hydrochlorothiazide as the Diuretic of Choice for Hypertension: Time to Kick the Habit. PMID- 26821627 TI - Pulse Pressure and Risk for Cardiovascular Events in Patients With Atherothrombosis: From the REACH Registry. AB - BACKGROUND: Pulse pressure (PP) provides valuable prognostic information in specific populations, but few studies have assessed its value on cardiovascular outcomes in a broad, worldwide population. OBJECTIVES: The aim of this study was to determine whether PP is associated with major adverse cardiovascular outcomes, independently of mean arterial pressure. METHODS: Participants from the international REACH (Reduction of Atherothrombosis for Continued Health) registry, which evaluates subjects with clinical atherothrombotic disease or risk factors for its development, were examined. Those with incomplete 4-year follow up or PP data (final n = 45,087) were excluded. Univariate and multivariate regression analyses were performed to determine the association between PP and cardiovascular outcomes, including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, all myocardial infarction, all stroke, cardiovascular hospitalization, and a combined outcome. PP was analyzed as a continuous and categorical (i.e., by quartile) variable. RESULTS: The mean age of the cohort was 68 +/- 10 years, 35% were women, and 81% were treated for hypertension. The mean blood pressure was 138 +/- 19/79 +/- 11 mm Hg, rendering a mean PP of 49 +/- 16 mm Hg. On univariate analysis, increasing PP quartile was associated with worse outcomes (p < 0.05 for all comparisons). After adjusting for sex, age, current smoking status, history of hypercholesterolemia, history of diabetes, aspirin use, statin use, blood pressure medication use, and mean arterial pressure, PP quartile was still associated with all outcomes except all stroke and cardiovascular death (p < 0.05 for all comparisons). Analysis of PP as a continuous variable yielded similar results. CONCLUSIONS: In an international cohort of high-risk subjects, PP, a readily available hemodynamic parameter, is associated with multiple adverse cardiovascular outcomes and provides prognostic utility beyond that of mean arterial pressure. PMID- 26821628 TI - Pulse Pressure: How Valuable as a Diagnostic and Therapeutic Tool? PMID- 26821630 TI - Genetic Causality in Complex Traits: The Case of Uric Acid. PMID- 26821632 TI - Being BOLD in Critical Limb Ischemia. PMID- 26821631 TI - Blood Oxygenation Level-Dependent CMR-Derived Measures in Critical Limb Ischemia and Changes With Revascularization. AB - BACKGROUND: Use of blood oxygenation level-dependent cardiovascular magnetic resonance (BOLD-CMR) to assess perfusion in the lower limb has been hampered by poor reproducibility and a failure to reliably detect post-revascularization improvements in patients with critical limb ischemia (CLI). OBJECTIVES: This study sought to develop BOLD-CMR as an objective, reliable clinical tool for measuring calf muscle perfusion in patients with CLI. METHODS: The calf was imaged at 3-T in young healthy control subjects (n = 12), age-matched control subjects (n = 10), and patients with CLI (n = 34). Signal intensity time curves were generated for each muscle group and curve parameters, including signal reduction during ischemia (SRi) and gradient during reactive hyperemia (Grad). BOLD-CMR was used to assess changes in perfusion following revascularization in 12 CLI patients. Muscle biopsies (n = 28), obtained at the level of BOLD-CMR measurement and from healthy proximal muscle of patients undergoing lower limb amputation (n = 3), were analyzed for capillary-fiber ratio. RESULTS: There was good interuser and interscan reproducibility for Grad and SRi (all p < 0.0001). The ischemic limb had lower Grad and SRi compared with the contralateral asymptomatic limb, age-matched control subjects, and young control subjects (p < 0.001 for all comparisons). Successful revascularization resulted in improvement in Grad (p < 0.0001) and SRi (p < 0.0005). There was a significant correlation between capillary-fiber ratio (p < 0.01) in muscle biopsies from amputated limbs and Grad measured pre-operatively at the corresponding level. CONCLUSIONS: BOLD CMR showed promise as a reliable tool for assessing perfusion in the lower limb musculature and merits further investigation in a clinical trial. PMID- 26821633 TI - Implantable Cardioverter-Defibrillators at End of Battery Life: Opportunities for Risk (Re)-Stratification in ICD Recipients. AB - Although implantable cardioverter-defibrillators (ICDs) are frequently viewed as a lifelong commitment in that patients are routinely scheduled for generator exchange (GE) at end of battery life, several considerations should prompt a reevaluation of risks and benefits before GE. Compared with initial ICD implant, patients receiving replacement devices are older, and have more comorbidities and shorter life expectancy, all of which may limit the benefit of ICD therapy following GE. Additionally, GE is associated with significant complications, including infection, which may increase the risk of mortality. In this paper, we review recent data regarding opportunities for risk stratification before GE, with a particular focus on those with improved left ventricular function and those who have not experienced ICD therapies during the first battery life. We also provide a broader perspective on ICD therapy, focusing on how decisions regarding GE may affect goals of care at the end of life. PMID- 26821634 TI - Safety and Efficacy of the Subcutaneous Implantable Defibrillator. AB - Multiple randomized, multicenter trials have established the role of the implantable cardioverter-defibrillator (ICD) in the treatment and prevention of sudden cardiac death. However, transvenous ICD leads have significant short- and long-term complications, offsetting some of the benefit of this therapy. This has led to the development of the entirely subcutaneous ICD. This system is safe and effective, avoiding the need for intravascular leads. It is best suited for patients at low risk for pacing and increased risk for transvenous lead complications. Ongoing randomized and long-term registries will help identify the optimal role of this device in clinical practice. PMID- 26821635 TI - Statin Initiation During Childhood in Patients With Familial Hypercholesterolemia: Consequences for Cardiovascular Risk. PMID- 26821629 TI - Causal Assessment of Serum Urate Levels in Cardiometabolic Diseases Through a Mendelian Randomization Study. AB - BACKGROUND: Although epidemiological studies have reported positive associations between circulating urate levels and cardiometabolic diseases, causality remains uncertain. OBJECTIVES: Through a Mendelian randomization approach, we assessed whether serum urate levels are causally relevant in type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), ischemic stroke, and heart failure (HF). METHODS: This study investigated 28 single nucleotide polymorphisms known to regulate serum urate levels in association with various vascular and nonvascular risk factors to assess pleiotropy. To limit genetic confounding, 14 single nucleotide polymorphisms exclusively associated with serum urate levels were used in a genetic risk score to assess associations with the following cardiometabolic diseases (cases/controls): T2DM (26,488/83,964), CHD (54,501/68,275), ischemic stroke (14,779/67,312), and HF (4,526/18,400). As a positive control, this study also investigated our genetic instrument in 3,151 gout cases and 68,350 controls. RESULTS: Serum urate levels, increased by 1 SD due to the genetic score, were not associated with T2DM, CHD, ischemic stroke, or HF. These results were in contrast with previous prospective studies that did observe increased risks of these 4 cardiometabolic diseases for an equivalent increase in circulating urate levels. However, a 1 SD increase in serum urate levels due to the genetic score was associated with increased risk of gout (odds ratio: 5.84; 95% confidence interval: 4.56 to 7.49), which was directionally consistent with previous observations. CONCLUSIONS: Evidence from this study does not support a causal role of circulating serum urate levels in T2DM, CHD, ischemic stroke, or HF. Decreasing serum urate levels may not translate into risk reductions for cardiometabolic conditions. PMID- 26821636 TI - Association of Hemoglobin A1c Levels With Cardiovascular Disease and Mortality in Chinese Patients With Diabetes. PMID- 26821637 TI - Plaque Characterization by Coronary Computed Tomography Angiography and Association With Acute Coronary Syndrome. PMID- 26821638 TI - Reply: Plaque Characterization by Coronary Computed Tomography Angiography and Association With Acute Coronary Syndrome. PMID- 26821639 TI - When Is TAVR in Patients With Severe Aortic Stenosis Deemed Extreme Risk for Surgery Appropriate? PMID- 26821640 TI - Reply: When is TAVR in Patients With Severe Aortic Stenosis Deemed Extreme Risk for Surgery Appropriate? PMID- 26821642 TI - Lessons Learned After 15 Years of Circumferential Bodylift Surgery. AB - Circumferential bodylift is a powerful procedure for achieving dramatic and natural body contouring changes in the massive weight loss patient. The care of these patients has raised our awareness of several important issues including safety, nutritional status, skin quality, recurrent laxity, surgical steps, and postoperative scars. Integration of this knowledge with various technical modifications over the last 15 years has improved our care for this cohort. We have not only seen a rise in the number of surgeries performed, but also the development of principles, techniques, and details that the authors feel necessary to share to achieve improved contour and more predictable outcomes. LEVEL OF EVIDENCE 4: Therapeutic. PMID- 26821641 TI - Why reinvent the wheel? Building new proteins based on ready-made parts. AB - We protein engineers are ambivalent about evolution: on the one hand, evolution inspires us with myriad examples of biomolecular binders, sensors, and catalysts; on the other hand, these examples are seldom well-adapted to the engineering tasks we have in mind. Protein engineers have therefore modified natural proteins by point substitutions and fragment exchanges in an effort to generate new functions. A counterpoint to such design efforts, which is being pursued now with greater success, is to completely eschew the starting materials provided by nature and to design new protein functions from scratch by using de novo molecular modeling and design. While important progress has been made in both directions, some areas of protein design are still beyond reach. To this end, we advocate a synthesis of these two strategies: by using design calculations to both recombine and optimize fragments from natural proteins, we can build stable and as of yet un-sampled structures, thereby granting access to an expanded repertoire of conformations and desired functions. We propose that future methods that combine phylogenetic analysis, structure and sequence bioinformatics, and atomistic modeling may well succeed where any one of these approaches has failed on its own. PMID- 26821643 TI - Effect of Tissue Adhesives on Seroma Incidence After Abdominoplasty: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Tissue adhesives (TAs) are widely utilized in abdominoplasty to reduce postoperative seroma. However, current literature regarding TAs in abdominoplasty is limited to small studies and the findings of single institutions. OBJECTIVES: The authors reviewed the current literature regarding the effects of TAs on seroma formation and other endpoints following abdominoplasty, and summarized the types of TAs and application techniques that have been described to date. METHODS: A systematic review of the Medline, Embase, Web of Science, and Cochrane databases was conducted to identify randomized controlled trials (RCTs) in which the numbers of patients who experienced seroma after abdominoplasty were indicated. The Cochrane Collaboration's tool for assessing risk of bias was applied. RESULTS: Seven studies were included in a descriptive review, 5 of which were RCTs. Data from the 5 RCTs were pooled for a meta-analysis. Patients who received TAs following abdominoplasty had a similar incidence of seroma compared with patients who did not receive TAs. However, the total drainage volume was significantly lower for patients who received TAs. CONCLUSIONS: There is a paucity of high-quality evidence to support the delivery of TAs to prevent seroma formation after abdominoplasty. Well-designed RCTs are needed to assess with confidence the overall effects of TAs in abdominoplasty. LEVEL OF EVIDENCE: 2 Therapeutic. PMID- 26821644 TI - Development and psychometric validation of a scoring questionnaire to assess healthy lifestyles among adolescents in Catalonia. AB - BACKGROUND: Lifestyle is intimately related to health. A questionnaire that specifically scores the healthiness of lifestyle of Catalan adolescents is needed. The objective of this study was to develop and validate a scoring questionnaire called VISA-TEEN to assess the healthy lifestyle of young Catalans that can be answered quickly and user-friendly. METHODS: A lifestyle questionnaire was developed based on the analysis of contributions from two focus groups, one with adolescents and the other with people who work with them (teachers and doctors). A panel of experts validated the content of items that were ultimately selected for the VISA-TEEN questionnaire. Three hundred ninety six adolescents (215 boys and 181 girls, age = 13-19 years) completed the VISA TEEN. Internal consistency was assessed using Cronbach's alpha (alpha) reliability coefficient. Test-retest reliability, using an intraclass correlation coefficient (ICC), was calculated based on scores attained two weeks apart. Construct validity was assessed by the extraction of components with an exploratory factor analysis. The relationship between the scores was measured using the health-related quality of life (HRQoL) KIDSCREEN-10 Index (the relationship was assessed by calculating Pearson's r correlation coefficient). The association of scores in the VISA-TEEN for self-rated health (SRH) was also examined by executing an analysis of variance (ANOVA) between the different categories of this variable. We also calculated the index of fit for factor scales (IFFS) for each component, as well as the discriminatory power of the instrument using Ferguson's delta (delta) coefficient. RESULTS: The VISA-TEEN questionnaire showed acceptable reliability (alpha = 0.66, alphaest = 0.77) and a very good test-retest agreement (ICC = 0.860). It could be broken down into the following five components, all with an acceptable or very good IFFS (0.7-0.96): diet, substance abuse, physical activity, Rational Use of Technological Leisure (RUTL), and hygiene. Scores on the VISA-TEEN showed significant correlation with the KIDSCREEN index (r = 0.21, p < 0.001) and were associated with SRH (p < 0.001). The discriminatory power was found to be delta = 0.97. CONCLUSIONS: The VISA-TEEN questionnaire developed to study the lifestyle of Catalan adolescents is a valid instrument to apply in this population as it is shown in the present psychometric tests to understand the role of lifestyle in the health of teenagers or to test the efficacy of health campaigns intended to improve teenagers' lifestyle. PMID- 26821645 TI - Use of prophylactic uterotonics during the third stage of labor: a survey of provider practices in community health facilities in Sierra Leone. AB - BACKGROUND: Postpartum hemorrhage remains the leading cause of maternal mortality worldwide. Administration of uterotonics during the third stage of labor is a simple and well established intervention that can significantly decrease the development of postpartum hemorrhage. Little is known about the use of prophylactic uterotonics in peripheral health centers, where the majority of normal deliveries occur. The purpose of this study is to assess health provider current practices and determinants to the use of prophylactic uterotonics in Sierra Leone, a country with one of the highest maternal mortality ratios worldwide. METHODS: This is a mixed methods study using descriptive cross sectional survey and qualitative interviews in community health facilities in Freetown, Sierra Leone following a comprehensive training on postpartum hemorrhage. Facilities and providers were surveyed between May and June 2014. Qualitative methods were used to identify barriers and facilitators to the use of prophylactic uterotonics. RESULTS: A total of 134 providers were surveyed at 39 periphreal health facilities. Thirteen facilities (39 %) reported an inconsistent supply of oxytocin. The majority of facilities (64 %) stored oxytocin at room temperature. Provider level, in-service training, and leadership role were significantly associated with prophylactic uterotonic use. Overall, 62 % of providers reported routine use. Midwives were most likely to routinely administer uterotonics (93 %), followed by community health officers/assistants (78 %), maternal and child health aides (56 %), and state-enrolled community health nurses (52 %). Of the providers who received in-service training, 67 % reported routine use; of those with no in-service training, 42 % reported routine use. Qualitative analysis revealed that facility protocols, widespread availability, and provider perception of utility facilitated routine use. Common barriers reported included inconsistent supply of uterotonics, lack of knowledge regarding timely administration, and provider attitude regarding utility of uterotonics following normal deliveries. CONCLUSION: There is considerable room for improvement in availability and administration of prophylactic uterotonics. Understanding barriers to routine use may aid in developing multifaceted pre service and in-service training interventions designed to improve routine intrapartum care. PMID- 26821646 TI - Developing a core outcome measurement set for clinical trials in acute diarrhoea. AB - AIM: The Working Group on Acute Diarrhoea, part of The Consensus Group on Outcome Measures Made in Paediatric Enteral Nutrition Clinical Trials, previously developed a core outcome set for clinical trials on acute diarrhoea. This study aimed to create a core outcome measurement set to complement it. METHODS: The study had three phases. The first identified how the literature defined core outcome measures in clinical trials on acute diarrhoea and measured outcomes. The second phase used a questionnaire to seek the views of 109 leading researchers and clinicians in this specialist field. The third phase achieved a consensus on the core outcome measurement set. RESULTS: First, we identified 52 different measurement instruments or definitions. A questionnaire was then used to ask our experts what they thought were the most valid core outcome measurement instruments or definitions for each measure and 53 (49%) responded. Core outcome measurement instruments were then developed, including definitions of diarrhoea and acute gastroenteritis, diarrhoea duration, dehydration, the need for hospitalisation, discharge criteria and duration of hospitalisation. CONCLUSION: The outcome measurement set can be used to evaluate therapeutic or preventive strategies and can be recommended for use in future acute diarrhoea trials. PMID- 26821647 TI - The Hippo signalling pathway maintains quiescence in Drosophila neural stem cells. AB - Stem cells control their mitotic activity to decide whether to proliferate or to stay in quiescence. Drosophila neural stem cells (NSCs) are quiescent at early larval stages, when they are reactivated in response to metabolic changes. Here we report that cell-contact inhibition of growth through the canonical Hippo signalling pathway maintains NSC quiescence. Loss of the core kinases hippo or warts leads to premature nuclear localization of the transcriptional co-activator Yorkie and initiation of growth and proliferation in NSCs. Yorkie is necessary and sufficient for NSC reactivation, growth and proliferation. The Hippo pathway activity is modulated via inter-cellular transmembrane proteins Crumbs and Echinoid that are both expressed in a nutrient-dependent way in niche glial cells and NSCs. Loss of crumbs or echinoid in the niche only is sufficient to reactivate NSCs. Finally, we provide evidence that the Hippo pathway activity discriminates quiescent from non-quiescent NSCs in the Drosophila nervous system. PMID- 26821648 TI - Diagnostic value of end tidal capnography in patients with hyperglycemia in the emergency department. AB - BACKGROUND: Diabetic Ketoacidosis (DKA) is a potentially life-threatening emergency that requires prompt diagnosis and treatment. In paediatric populations an end tidal capnography value greater than 36 mmHg was found to be 100 % sensitive in ruling out DKA. METHODS: A cross sectional observational study of adults >= 17 years of age presenting to the emergency department between January 2014 and May 2014 with glucose > 550 mg/dL. In all patients, nasal capnography and venous blood gas analysis were performed prior to any insulin or intravenous fluid administration. The diagnosis of DKA was based on the presence of anion gap metabolic acidosis, hyperglycaemia and ketonemia. The overall diagnostic performance (area under the curve [AUC]), sensitivity, specificity and likelihood ratios at different end tidal CO2 (ETCO2) cut-offs were determined. RESULTS: 71 patients were enrolled in the study of which 21 (30 %) met the diagnosis of DKA. The area under the curve for ETCO2 was 0.95 with a 95 % CI of 0.91 to 0.99. Test sensitivity for DKA at ETCO2 level >=35 mmHg was 100 % (95 % CI, 83.9-100). An ETCO2 level <= 21 mmHg was 100 % specific (95 % CI, 92.9-100.0) for DKA. CONCLUSION: Nasal capnography exhibits favourable diagnostic performance in detecting patients with or without DKA among those who present to the emergency department with a glucometer reading > 550 mg/dL. PMID- 26821649 TI - Genome-wide association study on stem rust resistance in Kazakh spring barley lines. AB - BACKGROUND: Stem rust (SR) is one of the most economically devastating barley diseases in Kazakhstan, and in some years it causes up to 50 % of yield losses. Routine conventional breeding for resistance to stem rust is almost always in progress in all Kazakhstan breeding stations. However, molecular marker based approach towards new SR resistance genes identification and relevant marker assisted selection had never been employed in Kazakhstan yet. In this study, as a preliminary step the GWAS (genome-wide association study) mapping was applied in attempt to identify reliable SNP markers and quantitative trait loci (QTL) associated with resistance to SR. RESULTS: Barley collection of 92 commercial cultivars and promising lines was genotyped using a high-throughput single nucleotide polymorphism (9,000 SNP) Illumina iSelect array. 6,970 SNPs out of 9,000 total were polymorphic and scorable. 5,050 SNPs out of 6,970 passed filtering threshold and were used for association mapping (AM). All 92 accessions were phenotyped for resistance to SR by observing adult plants in artificially infected plots at the Research Institute for Biological Safety Problems in Dzhambul region of Kazakhstan. GLM analysis allowed the identification of 15 SNPs associated with the resistance at the heading time (HA) phase, and 2 SNPs at the seed's milky-waxy maturity (SM) phase. However, after application of 5 % Bonferroni multiple test correction, only 2 SNPs at the HA stage on the same position of chromosome 6H can be claimed as reliable markers for SR resistance. The MLM analysis after the Bonferroni correction did not reveal any associations in this study, although distribution lines in the quantile-quantile (QQ) plot indicates that overcorrection in the test due to both Q and K matrices usage. CONCLUSIONS: Obtained data suggest that genome wide genotyping of 92 spring barley accessions from Kazakhstan with 9 K Illumina SNP array was highly efficient. Linkage disequilibrium based mapping approach allowed the identification of highly significant QTL for the SR resistance at the HA phase of growth on chromosome 6H. On the other hand, no significant QTL was detected at the SM phase, assuming that for a successful GWASmapping experiment a larger size population with more diverse genetic background should be tested. Obtained results provide additional information towards better understanding of SR resistance in barley. PMID- 26821650 TI - Post-traumatic growth of children affected by the Great East Japan Earthquake and their attitudes to memorial services and media coverage. AB - AIMS: Post-traumatic growth (PTG) refers to positive changes that result from coping with a major life crisis or a traumatic event. Factors influencing PTG in youth have not been well characterized but could have a great impact on overall maturation. METHODS: Fourth to ninth graders (n = 3337) attending elementary or junior high schools located in a district severely damaged by the Great East Japan Earthquake completed a questionnaire, including the revised Posttraumatic Growth Inventory for Children (PTGI-C-R) along with the Post Traumatic Stress Symptoms for Children 15 items (PTSSC-15), 31 months after the event. Experience of the disaster, prior traumatic experiences, and attitudes toward memories of the disaster (rumination) were scored by their caregivers and teachers, and effects of these factors on PTG were evaluated. RESULTS: There were no significant associations between PTGI-C-R and sex or experiences of the disaster. However, PTGI-C-R was negatively correlated with age (r = -0.132, P < 0.001). There was significant but very weak negative correlation between PTGI-C-R and PTSSC-15 among the children (r = -0.096, P < 0.001). PTGI-C-R was significantly associated with positive attitudes to memorial services (P < 0.001) and media coverage (P < 0.05). CONCLUSION: Positive attitudes to deliberate rumination may facilitate PTG in children following natural disasters. PMID- 26821651 TI - Conifer flavonoid compounds inhibit detoxification enzymes and synergize insecticides. AB - Detoxification by glutathione S-transferases (GSTs) and esterases are important mechanisms associated with insecticide resistance. Discovery of novel GST and esterase inhibitors from phytochemicals could provide potential new insecticide synergists. Conifer tree species contain flavonoids, such as taxifolin, that inhibit in vitro GST activity. The objectives were to test the relative effectiveness of taxifolin as an enzyme inhibitor and as an insecticide synergist in combination with the organophosphorous insecticide, Guthion (50% azinphos methyl), and the botanical insecticide, pyrethrum, using an insecticide-resistant Colorado potato beetle (CPB) Leptinotarsa decemlineata (Say) strain. Both taxifolin and its isomer, quercetin, increased the mortality of 1(st) instar CPB larvae after 48h when combined with Guthion, but not pyrethrum. Taxifolin had greater in vitro esterase inhibition compared with the commonly used esterase inhibitor, S, S, S-tributyl phosphorotrithioate (DEF). An in vivo esterase and GST inhibition effect after ingestion of taxifolin was measured, however DEF caused a greater suppression of esterase activity. This study demonstrated that flavonoid compounds have both in vitro and in vivo esterase inhibition, which is likely responsible for the insecticide synergism observed in insecticide resistant CPB. PMID- 26821652 TI - Inhibitory effect and enzymatic analysis of E-cinnamaldehyde against sclerotinia carrot rot. AB - This study was conducted to determine the inhibitory effect of E-cinnamaldehyde (EC) against causal agent of storage carrot rot, Sclerotinia sclerotiorum, under in vivo and in vitro conditions. Based on the results, EC was able to completely inhibit mycelial growth of three isolates (P>0.05) in both volatile and contact phases after 6days at the concentrations 200MUl and 1MUl/ml, respectively. In addition, EC at concentrations 1 and 10MUl/ml completely inhibited carpogenic germination of three isolates. The results of in vivo trials showed that EC at the concentration of 10MUl/ml was able to control the disease caused by isolates 1 and 3. However the disease caused by isolate 2 was inhibited with the concentration of 20MUl/ml. In enzyme analyses, the activity of polyphenoloxidase and peroxidase did not change in the inoculated carrots after application of EC. Furthermore, the level of phenylalanine ammonia lyase decreased. These results indicated that EC does not have any potential to be considered as resistance inducers against sclerotinia carrot rot. PMID- 26821653 TI - Effects of 10-hydroxycamptothecin on intrinsic mitochondrial pathway in silkworm BmN-SWU1 cells. AB - 10-Hydroxycamptothecin (HCPT), a plant alkaloid isolated from Camptotheca acuminate, is known as a planted-derived insecticide, however, the specific mechanism in insect cells is still unclear. In this study, we treated the ovarian cell line of the silkworm, BmN-SWU1, with different HCPT doses for durations ranging from 0 to 72h. The apoptosis morphology was evident after 72h of incubation and included cell protuberance, concentrated cytoplasm and apoptotic bodies. We observed DNA fragmentation and cell apoptosis after HCPT treatment. The disruption of mitochondrial distribution, activation of the intracellular mitochondrial permeability transition pore, and release of cytochrome c during HCPT-induced apoptosis in dose and time-dependent manner indicate the involvement of mitochondria in BmN-SWU1 cells. Caspase-9 and -3 activities increased gradually with the duration of incubation time. In conclusion, HCPT has a significant effect to initiate the intrinsic mitochondrial pathway in silkworm cells, providing a theoretical basis for better application of plant-derived insecticide in pest control. PMID- 26821654 TI - Knockdown of NADPH-cytochrome P450 reductase results in reduced resistance to buprofezin in the small brown planthopper, Laodelphax striatellus (fallen). AB - NADPH-cytochrome P450 reductase (CPR) plays an important role in cytochrome P450 function, and CPR knockdown in several insects leads to increased susceptibility to insecticides. However, a putative CPR gene has not yet been fully characterized in the small brown planthopper Laodelphax striatellus, a notorious agricultural pest in rice that causes serious damage by transmitting rice stripe and rice black-streaked dwarf viruses. The objective of this study was to clone the cDNA and to knock down the expression of the gene that encodes L. striatellus CPR (LsCPR) to further determine whether P450s are involved in the resistance of L. striatellus to buprofezin. First, the full-length cDNA of LsCPR was cloned and found to contain an open reading frame (ORF) encoding a polypeptide of 679 amino acids with a calculated molecular mass and isoelectric point of 76.92kDa and 5.37, respectively. The deduced amino acid sequence shares high identity with the CPRs of other insects (98%, 97%, 75% and 68% for Sogatella furcifera, Nilaparvata lugens, Cimex lectularius and Anopheles gambiae, respectively) and possesses the characteristic features of classical CPRs, such as an N-terminal membrane anchor and conserved domains for flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide phosphate (NADPH) binding. Phylogenetic analysis revealed that LsCPR is located in a branch along with the CPRs of other hemipteran insects. LsCPR mRNA was detectable in all examined body parts and developmental stages of L. striatellus, as determined by real-time quantitative PCR (qPCR), and transcripts were most abundant in the adult abdomen and in first-instar nymphs and adults. Ingestion of 200MUg/mL of LsCPR double-stranded RNA (dsLsCPR) by the planthopper for 5days significantly reduced the transcription level of LsCPR. Moreover, silencing of LsCPR caused increased susceptibility to buprofezin in a buprofezin-resistant (YN-BPF) strain but not in a susceptible (YN) strain. These data further suggested that the P450 mediated metabolic detoxification of xenobiotics might be an important mechanism for buprofezin resistance in L. striatellus. PMID- 26821655 TI - Effect of certain entomopathogenic fungi on oxidative stress and mortality of Periplaneta americana. AB - The present paper reports the effects of Metarhizium anisopliae, Isaria fumosoroseus and Hirsutella thompsonaii on Periplaneta americana. I. fumosoroseus and H. thompsonaii were cultured at 28+/-1 degrees C on potato carrot agar and M. anisopliae was cultured at 28+/-1 degrees C on potato dextrose agar for 14days. Conidial suspensions of fungi were given to cockroaches through different routes. M. anisopliae shows high virulence against adult cockroaches and mortality ranges from 38.65% to 78.36% after 48h. I. fumosoroseus and H. thompsonii show less virulence compared to M. anisopliae. We also investigated the effect of these three fungi on the activity of lactate dehydrogenase, lipid peroxidation and catalase in different tissues of the insect to gain an understanding of the different target site. The result suggested that the activity of lactate dehydrogenase, catalase and level of malondialdehyde varies in different organs and through different routes of exposure. Based on mortality percentages, all tested fungi had high potentials for biocontrol agents against P. americana. Our study reveals for the first time that I. fumosoroseus and H. thompsonaii fungal infections initiate oxidative stress in the midgut, fat body, whole body and hemolymph of cockroach thereby suggesting them to be the target organs for oxidative damage. PMID- 26821656 TI - Molecular basis of Cyperus difformis cross-resistance to ALS-inhibiting herbicides. PMID- 26821657 TI - Involvement of the processing step in the susceptibility/tolerance of two lepidopteran larvae to Bacillus thuringiensis Cry1Aa toxin. AB - Bacillus thuringiensis (Bt) Cry1A toxins are known for their effectiveness against lepidopteran insects. In this study, the entomopathogenic activity of Cry1Aa was investigated against two lepidopteran larvae causing serious threat to various crops, Spodoptera littoralis and Tuta absoluta. Contrarily to S. littoralis, which showed low susceptibility to Cry1Aa (40% mortality with 1MUg/cm(2)), T. absoluta was very sensitive to this delta-endotoxin (LC50 of 95.8ng/cm(2)). The different steps in the mode of action of this toxin on the two larvae were studied with the aim to understand the origin of their difference of susceptibility. Activation of the 130kDa Cry1Aa protein by T. absoluta larvae juice generated a 65kDa active toxin, whereas S. littoralis gut juice led to a complete degradation of the protoxin. The study of the interaction of the brush border membrane vesicles (BBMV) with purified biotinylated Cry1Aa toxin revealed six and seven toxin binding proteins in T. absoluta and S. littoralis BBMV, respectively. Midgut histopathology of Cry1Aa fed larvae demonstrated approximately similar damage caused by the toxin in the two larvae midguts. These results suggest that the activation step was strongly involved in the difference of susceptibility of the two larvae to Cry1Aa. PMID- 26821658 TI - The subunit gene Ldalpha1 of nicotinic acetylcholine receptors plays important roles in the toxicity of imidacloprid and thiamethoxam against Leptinotarsa decemlineata. AB - Nicotinic acetylcholine receptors (nAChRs) are pentameric ACh-gated ion channels. It is believed that nAChRs composed of different subunits may vary in their function and toxicological characteristics. Neonicotinoids are activators of nAChRs and important insecticides that are extensively used for crop protection and resistance has been developed by some pests. They are also major insecticides for the control of Leptinotarsa decemlineata, which is a destructive defoliator pest that invaded the Xinjiang region of China in the 1990s. However, little is known about the constitution or subunits of the target in this pest. In this study, the full-length cDNAs encoding four new nAChR subunits (named Ldalpha3, Ldalpha6, Ldalpha10, and Ldbeta1) were cloned from L. decemlineata. These genes encode 822-, 753-, 672-, and 759-amino acid proteins, respectively, which share typical features of insect nAChRs subunits and closely resemble the corresponding subunits of the nAChRs from Tribolium castaneum. Temporal and spatial expression analyses showed that these genes, as well as the previously identified Ldalpha1, Ldalpha2, and Ldalpha8 genes, are widely expressed in all developmental stages, including eggs, larvae of various instars, pupae, and adults. All genes monitored were expressed at higher levels in the head than in the thorax and abdomen, except for Ldalpha10. Dietary ingestion of double-stranded RNA bacterially expressed for Ldalpha1 (dsLdalpha1) significantly reduced the mRNA level of Ldalpha1 in treated larvae and adults by 48.0% and 78.6%, respectively. Among the non-target genes, Ldalpha3, Ldalpha9, and Ldbeta1 were significantly up-regulated in larvae. A toxicity bioassay showed that dsLdalpha1 treatment greatly decreased the sensitivity to imidacloprid and thiamethoxam in adults. The larval susceptibility to thiamethoxam but not to imidacloprid was also reduced because of the lower down-regulation of Ldalpha1. Thus, our results suggest that Ldalpha1 encodes a subunit of a functional nAChR that mediates the toxicity of imidacloprid and thiamethoxam against L. decemlineata and that the down regulation of Ldalpha1 might be an important mechanism for resistance and/or tolerance of L. decemlineata to neonicotinoids. PMID- 26821659 TI - Selection of relatively exact reference genes for gene expression studies in flixweed (Descurainia sophia) by quantitative real-time polymerase chain reaction. AB - The reliable gene expression analysis of a reverse transcription quantitative polymerase chain reaction (qRT-PCR) mainly depends on selecting suitable reference genes that can express stably under different experimental conditions. Thus far, no reference genes have been identified in flixweed. In this paper, 7 supposed reference genes were selected to evaluate their expression stabilities by qRT-PCR in flixweed under three conditions including different sampling times after tribenuron treatment, different organs, and different growth stages using geNorm, NormFinder, and BestKeeper statistical algorithms. The results showed that ACT7, UBC and 18SrRNA were the stable reference genes in all of the tested samples. ACT7 and UBC showed high stability in different sampling times after the tribenuron treatment. UBC and 18SrRNA were the most suitable genes for different organs and growth stages. This work confirmed the suitable reference genes of flixweed for a relatively accurate gene expression analysis under different experimental conditions. PMID- 26821660 TI - Genetic characterization of field-evolved resistance to phosphine in the rusty grain beetle, Cryptolestes ferrugineus (Laemophloeidae: Coleoptera). AB - Inheritance of resistance to phosphine fumigant was investigated in three field collected strains of rusty grain beetle, Cryptolestes ferrugineus, Susceptible (S strain), Weakly Resistant (Weak-R) and Strongly Resistant (Strong-R). The strains were purified for susceptibility, weak resistance and strong resistance to phosphine, respectively, to ensure homozygosity of resistance genotype. Crosses were established between S-strain*Weak-R, S-strain*Strong-R and Weak-R*Strong-R, and the dose mortality responses to phosphine of these strains and their F1, F2 and F1-backcross progeny were obtained. The fumigations were undertaken at 25 degrees C and 55% RH for 72h. Weak-R and Strong-R showed resistance factors of 6.3* and 505* compared with S-strain at the LC50. Both weak and strong resistances were expressed as incompletely recessive with degrees of dominance of -0.48 and -0.43 at the LC50, respectively. Responses of F2 and F1-backcross progeny indicated the existence of one major gene in Weak-R, and at least two major genes in Strong-R, one of which was allelic with the major factor in Weak R. Phenotypic variance analyses also estimated that the number of independently segregating genes conferring weak resistance was 1 (nE=0.89) whereas there were two genes controlling strong resistance (nE=1.2). The second gene, unique to Strong-R, interacted synergistically with the first gene to confer a very high level of resistance (~80*). Neither of the two major resistance genes was sex linked. Despite the similarity of the genetics of resistance to that previously observed in other pest species, a significant proportion (~15 to 30%) of F1 individuals survived at phosphine concentrations higher than predicted. Thus it is likely that additional dominant heritable factors, present in some individuals in the population, also influenced the resistance phenotype. Our results will help in understanding the process of selection for phosphine resistance in the field which will inform resistance management strategies. In addition, this information will provide a basis for the identification of the resistance genes. PMID- 26821661 TI - Modulation of the Ca(2+) signaling pathway by celangulin I in the central neurons of Spodoptera exigua. AB - Celangulin I is an insecticidal component isolated from Chinese bittersweet Celastrus angulatus. The present study explored the possible effects of celangulin I on the calcium signaling pathway, especially on the L-type Ca(2+) channel and the calcium channels in the endoplasmic reticulum in the central neurons isolated from the third instar larvae of Spodoptera exigua using whole cell patch-clamp and calcium imaging technique. The results showed that celangulin I could activate the high voltage-gated calcium channel at the concentration of 150MUM. The peak currents were increased by 17% of the initial value at the end of the 10-min recording after treated with celangulin I. The rises of intracellular calcium ion concentration ([Ca(2+)]i) in neurons treated by celangulin I showed that the effects of celangulin I were concentration dependent. Activation of the RyRs by ryanodine decreased the calcium release induced by celangulin I, indicating that celangulin I exerts effect on insect RyRs. Furthermore, we also provided evidence for the first time that celangulin I activates inositol 1,4,5-trisphosphate (IP3) sensitive intracellular calcium release channels in the endoplasmic reticulum third instar larvae neurons of S. exigua. Plausibly, these experimental results can explain the characteristic symptoms of anesthesia and paralysis in celangulin I treated insects. PMID- 26821662 TI - A point mutation (L1015F) of the voltage-sensitive sodium channel gene associated with lambda-cyhalothrin resistance in Apolygus lucorum (Meyer-Dur) population from the transgenic Bt cotton field of China. AB - In China, the green mirid bug, Apolygus lucorum (Meyer-Dur), has caused severe economic damage to many kinds of crops, especially the cotton and jujubes. Pyrethroid insecticides have been widely used for controlling this pest in the transgenic Bt cotton field. Five populations of A. lucorum collected from cotton crops at different locations in China were evaluated for lambda-cyhalothrin resistance. The results showed that only the population collected from Shandong Province exhibited 30-fold of resistance to lambda-cyhalothrin. Neither PBO nor DEF had obvious synergism when compared the synergistic ratio between SS and RR strain which was originated from the Shandong population. Besides, there were no statistically significant differences (p>0.05) in the carboxylesterase, glutathione S-transferase, or 7-ethoxycoumarin O-deethylase activities between the Shandong population and the laboratory susceptible strain (SS). The full length sodium channel gene named AlVSSC encoding 2028 amino acids was obtained by RT-PCR and rapid amplification of cDNA ends (RACE). One single point mutation L1015F in the AlVSSC was detected only in the Shandong population. Our results revealed that the L1015F mutation associated with pyrethroid resistance was identified in A. lucorum populations in China. These results will be useful for the rational chemical control of A. lucorum in the transgenic Bt cotton field. PMID- 26821663 TI - Hexaconazole-Cu complex improves the salt tolerance of Triticum aestivum seedlings. AB - Hexaconazole is one of the triazole complexes that are broadly used as systemic fungicides with non-traditional plant growth regulator properties. Hexaconazole Cu complex (Hex-Cu) is a new triazole derivative, and the biological effect of Hex-Cu has been rarely studied. In this work, we investigated the functions of Hex-Cu in regulating growth and the response to salt stress in the seedlings of Triticum aestivum. Pretreated with 60MUmolL(-1) Hex-Cu, the seedling plants got increased root/shoot ratio by 42.0%, and the contents of chlorophyll and soluble protein were also increased by 38.1% and 27.9%, respectively. Furthermore, Hex-Cu alleviated the growth inhibition caused by salt stress, enabled the seedlings to maintain a higher proline content and lower malondialdehyde accumulation. The functions of Hex-Cu in regulating the expression of proline synthetase (P5CS and P5CR) genes were investigated by quantitative real-time PCR (qPCR). Under 100mmolL(-1) NaCl stress, the expression of P5CS and P5CR in the seedlings by Hex Cu pretreatment were significantly up-regulated. It attributed to the enhanced salt tolerance in plants. PMID- 26821666 TI - Comparison Of Item-Level And Score-Level Typological Analysis: A Simulation Study. AB - A method of typological analysis was applied to computer-generated l 96-item "questionnaire" data for 100 cases, under a variety of conditions as to: a. response pattern differentiation in the data; b. similarity index used; c. criteria for the formation of clusters-types. 'Under each combination of conditions, analyses were carried out at both item-level and score-level (i.e., records reduced to 12 eight-item "scores"). The results showed a considerable advantage of score-level approach in the number, size, and replicability of clusters recovered. PMID- 26821664 TI - Sustained impact of a short small group course with systematic feedback in addition to regular clinical clerkship activities on musculoskeletal examination skills--a controlled study. AB - BACKGROUND: The discrepancy between the extensive impact of musculoskeletal complaints and the common deficiencies in musculoskeletal examination skills lead to increased emphasis on structured teaching and assessment. However, studies of single interventions are scarce and little is known about the time-dependent effect of assisted learning in addition to a standard curriculum. We therefore evaluated the immediate and long-term impact of a small group course on musculoskeletal examination skills. METHODS: All 48 Year 4 medical students of a 6 year curriculum, attending their 8 week clerkship of internal medicine at one University department in Berne, participated in this controlled study. Twenty seven students were assigned to the intervention of a 6*1 h practical course (4-7 students, interactive hands-on examination of real patients; systematic, detailed feedback to each student by teacher, peers and patients). Twenty-one students took part in the regular clerkship activities only and served as controls. In all students clinical skills (CS, 9 items) were assessed in an Objective Structured Clinical Examination (OSCE) station, including specific musculoskeletal examination skills (MSES, 7 items) and interpersonal skills (IPS, 2 items). Two raters assessed the skills on a 4-point Likert scale at the beginning (T0), the end (T1) and 4-12 months after (T2) the clerkship. Statistical analyses included Friedman test, Wilcoxon rank sum test and Mann-Whitney U test. RESULTS: At T0 there were no significant differences between the intervention and control group. At T1 and T2 the control group showed no significant changes of CS, MSES and IPS compared to T0. In contrast, the intervention group significantly improved CS, MSES and IPS at T1 (p < 0.001). This enhancement was sustained for CS and MSES (p < 0.05), but not for IPS at T2. CONCLUSIONS: Year 4 medical students were incapable of improving their musculoskeletal examination skills during regular clinical clerkship activities. However, an additional small group, interactive clinical skills course with feedback from various sources, improved these essential examination skills immediately after the teaching and several months later. We conclude that supplementary specific teaching activities are needed. Even a single, short-lasting targeted module can have a long lasting effect and is worth the additional effort. PMID- 26821665 TI - Caregiver perceptions of childhood weight: demographic moderators and correlates. AB - BACKGROUND: To examine whether ethnicity moderates the association between caregiver characteristics and perceptions of childhood weight and whether these perceptions are associated with their child's obesity status. METHODS: Caregivers recruited from paediatricians' offices (n = 453) completed a survey about childhood health; nurses weighed and measured the children. Caregivers reported their own weight and height, demographic information about their family and made ratings of healthy weight for children in general and for their own child in particular. RESULTS: African American caregivers were more likely to view heavier girls as healthier, but this association held only for lower income families or caregivers with higher body mass index. Hispanic caregivers were more likely to misperceive their own child's weight if either the caregiver or the child had a higher body mass index. Parents who perceived heavier weight as healthier or misperceived their own child's weight were more likely to have a child with obesity. This latter association held regardless of ethnicity. CONCLUSION: The association between ethnicity and perceptions of healthy childhood weight are complex. The relation between caregivers' perceptions of healthy weight and their own child's obesity status, however, was similar regardless of ethnicity. PMID- 26821668 TI - An Appropriate Test For Comparative Discriminatory Power. AB - Suppose PI and P2 are two competing discrimination procedures. 1Co com-, its are pare the relative discriminatory power of both procedures, test statistics are suggested for the hypothesis that Pl and P2 performed no better than, random assignment versus the alternative that P1 did significantly better than Pe. PMID- 26821667 TI - Replicability Of Factors Derived From Individual P-Technique Analyses. AB - Four hospitalized female schizophrenics performed self-ratings on a battery of variables for 60 consecutive days. The variables were factored, separately for each subject, and the factors were then rotated to solutions which were maximally invariant from each other. Factor matching among subjects was then assessed by congruence coefficients. The factors which replicated over persons appeared to be broad, second-order dimensions identifiable as Social Desirability, Extraversion and Anxiety. The results are discussed in relation to nomothetic vs. idiographic systems of psychology and the study of intraindividual change by P-technique as a methodology of clinical interest. PMID- 26821669 TI - A Smallest Space Analysis (Ssa) Of Potential Work Mobility. AB - This paper introduces a new methodological approach-smallest space analysis-to the examination of potential work mobility. Operational definition of such mobility is introduced in terms of amounts and kinds of organizational and occupational incentives which might be offered to an employee. Then empirical data on system analysts in Israel are used to test the structure of the definition. The potential mobility with respect to both organization and occupation is found to be structured essentially as expected. PMID- 26821670 TI - Some Statistical Considerations In Clustering With Binary Data. AB - A statistical theory of cluster homogeneity is developed for object:, scored on binary (0,l) variables. The theory utilizes two test statistics originally suggested by Tryon and Bailey (1970). The exact sampling distribution of the statistic H2,,, "squared homogeneity for cluster g on variable r" is derived under the assumption of a random assortment of 0's and 1's in the observed clusters. Formulas for the mean and variance of H,2, "the overall homogeneity for cluster g across all variables" are derived which may be used in con- junction with probability inequalities to carry out significance tests on this statistic. Comments concerning a framework for deriving metric distances between objects scored only on binary variables are also included. PMID- 26821671 TI - Acrophobia Factor Scores As A Function Of Pole Height And Habituation. AB - Thirty C57BL/ALB mice, fifteen male and fifteen female, were tested for "acrophobia" via the pole test. The animals were randomly distributed into three groups of 6, 12, or 24 inch (15.24, 30.48, or 60.96 cm) high poles:. Both factor scores and individual pole measures were analyzed by 2 x 3 x 5 ANOVA, with main effects for sex, pole height, and days of testing. The results provide experimental support for the interpretation of this factor as acrophobia-that is, the greater the pole height, the higher the factor score. The reduction of factor scores over days (habituation) is interpreted as an arousal-based response. PMID- 26821672 TI - Multivariate Analysis Of Intrinsic Individual Differences In Disjunctive Conceptual Behavior. AB - Since it is known that intrinsic individual differences increase with the complexity of the behavior and since it is suspected that no single response measure can adequately represent the learning process, the present study examined intrinsic individual differences in conceptual behavior with a multivariate model, three-mode factor analysis. Four response measures were selected according to their traditional or apparent importance to the analysis of concept learning. The number of errors, response latency, post-response time, and interresponse time were those selected to reflect the subject's performances on a figural, disjunctive conceptual behavior task. The analyses yielded five individual difference performance factors, three stage factors, and four response components indicating the importance of a multivariate representation of complex behavior. PMID- 26821673 TI - Flange Detection Cluster Analysis. AB - A clustering technique is described, the objective of which is to detect deviant subpopulations which deviate from a primary subpopulation in1 a well defined direction. The distributions of the primary and deviant subpopulations and the number of deviant subpopulations are initially unknown. Each deviant subpopulation is to be identified by means of a linear scale (an affine function of the observed variables) which distinguishes its members from those of the primary subpopulation. The approach consists of the following three steps: (1) the main cluster of sample points is identified; (2) the directions are determined in which there are the greatest number of outliers from the main cluster; (3) the statistical stability of each supposed outlier direction is tested. Our algorithm has been tested on both manufactured data and on real (MMPI) data. PMID- 26821674 TI - The Consequences Of Model Misspecification In Regression Analysis. AB - In ordinary least squares regression analysis the desired property of unbiasedness in estimated coefficients is contingent upon the correspondence of the fitted model with the true underlying data generating process. This paper focuses on developing a systematic characterization of the error forms resulting from model misspecification in single equation models. The consequences of model misspecification, for the error forms identified, are also evaluated. PMID- 26821675 TI - STUDYING CANONICAL ANALYSIS: COMMENTS ON BARCIKOWSKI AND STEVENS. AB - In their Monte Carlo study of canonical analysis, Barcikowski and Stevens evaluated the relative stability of canionical weights and loadings. This paper identifies some weaknesses in their study, suggests directions for future research in this area, and discusses interpretation of canonical analysis both in development and in cross-validation. PMID- 26821676 TI - Studying Canonical Analysis: A Reply To Thorndike's Comments. AB - Robert M. Thorndike (1976) commented on the results of a Monte Carlo study on the stability of canonical correlations, canonical weights, and canonical variate variable correlations (Barcikowski and Stevens, 1975). In this paper each of his comments are examined by the authors of the Monte Carlo Study. In addition, a possible solution to the large number of subjects necessary for stable weights and variate-variable correlations using ridge regression procedures is suggested. PMID- 26821677 TI - Multidimensional Perceptions Of The 1972 Presidential Election. AB - Five separate multidimensional scaling analyses, with a total of 2231 subjects and with measurement occasions varying from election day to about 14 months after election day, resulted in two stable dimensions of political perception. These dimensions were identified as Republican and Democratic evaluative dimensions. Significant changes in the saliencies of these dimensions over time were noted for the pro-McGovern subjects, but no such changes were found for the pro-Nixon subjects. Most of these findings were consistent with the previous literature in political perception. The publicity surrounding Watergate apparently did not affect the stability of the political perceptions. PMID- 26821679 TI - In silico analyses of heparin binding proteins expression in human periodontal tissues. AB - BACKGROUND: Periodontitis is described as a group of inflammatory diseases of the gingiva and supporting structures of the periodontium. The accumulation of plaque bacteria, which include putative periodontal pathogens, is known to initiate the disease but the host immune response is the major contributing factor for destruction of periodontal tissues. Proteins that bind to heparin heparin-binding protein (HBPs) play important roles in health and disease and interact with each other via networks known as 'heparin interactomes'. This study aimed at evaluating published datasets of HBPs and its role in periodontitis. METHODS: To elucidate the role of HBPs in periodontitis, bioinformatics analyses of published data was used. In silico analyses of published datasets were used to construct a putative HBPs interactome using an online database resource, 'STRING' (Search Tool for the Retrieval of Interacting Genes). RESULTS: PubMed searches identified 249 genes that were up regulated and 146 genes that were down regulated in periodontal disease, compared with periodontal disease-free gingival samples. In silico analyses using published datasets revealed 25 up-regulated and 23 down regulated HBPs in periodontitis. Of these HBPs; chemokines, such as CXCL12 was up regulated where as some of the matrixmetalloproteinases (MMPs; MMP-2 and MMP9) were up-regulated while MMP-14 was down regulated. CONCLUSIONS: The results indicate that HBP analyses will provide multiple targets for the biological mechanisms underlying periodontal disease (such as MMPs, cytokines and chemokines) that will have important clinical implications in the future drug design and management of periodontal disease. PMID- 26821678 TI - The fibroblast Tiam1-osteopontin pathway modulates breast cancer invasion and metastasis. AB - BACKGROUND: The tumor microenvironment has complex effects in cancer pathophysiology that are not fully understood. Most cancer therapies are directed against malignant cells specifically, leaving pro-malignant signals from the microenvironment unaddressed. Defining specific mechanisms by which the tumor microenvironment contributes to breast cancer metastasis may lead to new therapeutic approaches against advanced breast cancer. METHODS: We use a novel method for manipulating three-dimensional mixed cell co-cultures, along with studies in mouse xenograft models of human breast cancer and a histologic study of human breast cancer samples, to investigate how breast cancer-associated fibroblasts affect the malignant behaviors of breast cancer cells. RESULTS: Altering fibroblast Tiam1 expression induces changes in invasion, migration, epithelial-mesenchymal transition, and cancer stem cell characteristics in associated breast cancer cells. These changes are both dependent on fibroblast secretion of osteopontin and also long-lasting even after cancer cell dissociation from the fibroblasts, indicating a novel Tiam1-osteopontin pathway in breast cancer-associated fibroblasts. Notably, inhibition of fibroblast osteopontin with low doses of a novel small molecule prevents lung metastasis in a mouse model of human breast cancer metastasis. Moreover, fibroblast expression patterns of Tiam1 and osteopontin in human breast cancers show converse changes correlating with invasion, supporting the hypothesis that this pathway in tumor associated fibroblasts regulates breast cancer invasiveness in human disease and is thus clinically relevant. CONCLUSIONS: These findings suggest a new therapeutic paradigm for preventing breast cancer metastasis. Pro-malignant signals from the tumor microenvironment with long-lasting effects on associated cancer cells may perpetuate the metastatic potential of developing cancers. Inhibition of these microenvironment signals represents a new therapeutic strategy against cancer metastasis that enables targeting of stromal cells with less genetic plasticity than associated cancer cells and opens new avenues for investigation of novel therapeutic targets and agents. PMID- 26821680 TI - Psychopharmacology of chronic pain: a focus on antidepressants and atypical antipsychotics. AB - Chronic pain is considered one of the most prevalent causes of costly and disabling medical conditions. This review will define chronic pain and its categories and then will summarize the effectiveness and side effects associated with the use of various antidepressants, including the tricyclics, the selective serotonin reuptake inhibitors, the serotonin norepinephrine reuptake inhibitors, other miscellaneous antidepressants and the atypical antipsychotics in the treatment of chronic pain. PMID- 26821681 TI - Biomarkers in psoriatic arthritis: a systematic literature review. AB - Psoriatic arthritis (PsA) is characterized by chronic inflammation of peripheral joints and axial skeleton, associated with a strong genetic background. Clinics include enthesitis or dactylitis and extra-articular involvement as uveitis or inflammatory bowel disease, while treatment options range from nonsteroidal anti inflammatory drugs (NSAIDs) to biologics, targeting TNF alpha or Th17. No serum autoantibody is associated with PsA, while other biomarkers have been proposed for early diagnosis or to predict treatment response. To better discuss this area of growing interest we performed a systematic review of the literature on biomarkers in PsA. Our research retrieved 408 papers, and 38 were included in the analysis. Based on the available literature, we draw some recommendations for the use of biomarkers in the management of patients with PsA. PMID- 26821683 TI - Radiofrequency-induced heating versus mechanical stapler for pancreatic stump closure: in vivo comparative study. AB - PURPOSE: The aim of this study was to assess the capacity of two methods of surgical pancreatic stump closure in terms of reducing the risk of pancreatic fistula formation (POPF): radiofrequency-induced heating versus mechanical stapler. MATERIALS AND METHODS: Sixteen pigs underwent a laparoscopic transection of the neck of the pancreas. Pancreatic anastomosis was always avoided in order to work with an experimental model prone to POPF. Pancreatic stump closure was conducted either by stapler (ST group, n = 8) or radiofrequency energy (RF group, n = 8). Both groups were compared for incidence of POPF and histopathological alterations of the pancreatic remnant. RESULTS: Six animals (75%) in the ST group and one (14%) in the RF group were diagnosed with POPF (p = 0.019). One animal in the RF group and three animals in the ST group had a pseudocyst in close contact with both pancreas stumps. On day 30 post-operation (PO), almost complete atrophy of the exocrine distal pancreas was observed when the main pancreatic duct was efficiently sealed. CONCLUSIONS: Our findings suggest that RF-induced heating is more effective at closing the pancreatic stump than mechanical stapler and leads to the complete atrophy of the distal remnant pancreas. PMID- 26821682 TI - Possible role of asymmetric dimethylarginine (ADMA) in prediction of perinatal outcome in preeclampsia and fetal growth retardation related to preeclampsia. AB - OBJECTIVE: The objective of this study is to investigate maternal serum and neonatal umbilical cord asymmetric dimethylarginine (ADMA) levels in prediction of perinatal prognosis in pregnancies with preeclampsia (PE) and fetal intrauterine growth retardation (IUGR) accompanying PE (PE + IUGR). METHODS: Maternal serum ADMA (msADMA) and neonatal umbilical cord ADMA (ucADMA) levels were studied from 34 patients with PE, 25 patients with PE + IUGR, and 30 healthy pregnant controls in this prospective case-control study. Umbilical artery Doppler indices of fetuses, birth weights, Apgar scores, umbilical artery pH measurements of neonates, and admissions to neonatal intensive care unit (NICU) were recorded. RESULTS: Median msADMA was significantly higher in PE and PE + IUGR groups (p = 0.024 and p = 0.011, respectively), and ucADMA was significantly higher in PE and PE + IUGR groups than the control group (p = 0.029 and p = 0.018, respectively). Median msADMA and ucADMA levels were significantly higher in the PE + IUGR group than the PE group (p = 0.019 and 0.021, respectively). ucADMA levels did not correlate with fetal umbilical arterial blood flow neither in the PE nor in the PE + IUGR group (p = 0.518 and p = 0.892, respectively). None was related with neonatal umbilical artery pH or NICU admission rates. CONCLUSIONS: msADMA and ucADMA correlated with severity of PE. msADMA and ucADMA failed to predict perinatal outcome in patients with PE and PE + IUGR. PMID- 26821684 TI - Current Methods for the Analysis of Selected Novel Nutrients in Infant Formulas and Adult Nutritionals. AB - Infant formula is designed to provide the human infant with a sole source of nutrition and it is intended to imitate breast milk. In recent years, advances in the science of infant nutrition have led to an increasing number of novel ingredients that are supplemented into infant formula. As the list of these nutritionally important nutrients is lengthy, this review summarizes contemporary analytical methods that have been applied to a representative selection (lutein, carnitine, choline, nucleotides, inositol, taurine, sialic acid, gangliosides, triacylglycerides, oligosaccharides, alpha-lactalbumin, and lactoferrin). PMID- 26821685 TI - Early diagnosis by FNA cytology should not influence the outcome of differentiated thyroid cancer. AB - In oncology, the early cancer detection is recognized as associated with good patient's prognosis. Then, one could expect that differentiated thyroid carcinoma (DTC) undergone fine-needle aspiration cytology (FNA) early have better outcome. Aim of this study was to investigate if DTC prognosis is improved by early FNA diagnosis. DTCs followed-up at our institution were included. Information about initial management of thyroid lesion, FNA, surgery, and postoperative follow-up was collected. Cytologies were classified according to British Thyroid Association (BTA). The final series comprised 219 DTCs, of which 22 (10%) recurred. The length of time between nodule appearance and cancer treatment was significantly (p<0.0001) shorter in patients who had undergone FNA than those who had not. In the FNA group, 73 patients underwent biopsy within six months, 25 at 7-12 months, and 43 after at least one year. Regardless of this highly significant (p<0.0001) difference, the results of TNM staging and cancer recurrence rate were no different between these three subgroups. This result was confirmed in DTCs larger than 1 cm submitted to FNA within 12 months or later. When we evaluated the impact of nodule's presentation on DTC outcome, clinically discovered cancers were significantly associated with relapse (OR 2.81) and advanced TNM stages (p=0.03). These data show a lack of clinical impact of the delayed diagnosis of DTC. Also, the postoperative outcome of these patients should not be influenced by the timing of FNA. Instead, DTC patients with preoperative clinical nodule appearance should be considered at higher risk of relapse. PMID- 26821686 TI - Knowledge central: A central role for knowledge attributions in social evaluations. AB - Five experiments (N = 1710) demonstrate the central role of knowledge attributions in social evaluations. In Experiments 1-3, we manipulated whether an agent believes, is certain of, or knows a true proposition and asked people to rate whether the agent should perform a variety of actions. We found that knowledge, more so than belief or certainty, leads people to judge that the agent should act. In Experiments 4-5, we investigated whether attributions of knowledge or certainty can explain an important finding on how people act based on statistical evidence, known as "the Wells effect". We found that knowledge attributions, but not certainty attributions, mediate this effect on decision making. PMID- 26821687 TI - "Get With the Guideline" Treatment With Statin. PMID- 26821688 TI - Outcome of Patients Treated by Cardiac Resynchronization Therapy Using a Quadripolar Left Ventricular Lead. AB - BACKGROUND: Not all heart failure (HF) patients benefit from cardiac resynchronization therapy (CRT). We assessed whether choosing the site of left ventricular (LV) pacing by a quadripolar lead may improve response to CRT. METHODS AND RESULTS: We prospectively randomized 23 patients with HF (67+/-11 years; 21 males) to CRT with a quadripolar LV lead (group 1, with the LV pacing site chosen on the basis of QRS shortening using simultaneous biventricular pacing), and 20 patients (71+/-6 years; 16 males) to a bipolar LV lead (group 2, with devices programmed with a conventional tip-to-ring configuration). New York Heart Association (NYHA) class and LV ejection fraction (EF) by 2D echocardiography were assessed at baseline and after 3 months. The baseline EF was not different between the 2 groups (25+/-6% group 1 vs. 27+/-3% group 2; P=0.22), but after 3 months EF was higher in group 1 (35+/-13% group 1 vs. 31+/ 4% group 2; P<0.001). A reduction in at least 1 NYHA class at 3 months was observed in 22 (96%) and 12 (60%) of group 1 and group 2 patients, respectively (P<0.05). CONCLUSIONS: CRT with a quadripolar LV lead was associated with an improvement of EF greater than that observed in patients receiving a bipolar LV lead. In devices with a quadripolar lead, CRT programming based on the best QRS shortening is reliable and effective. (Circ J 2016; 80: 613-618). PMID- 26821689 TI - Here Comes a Novel Heart-Rate Reducing Therapy in Heart Failure Treatment. PMID- 26821690 TI - Impact of Insulin Resistance on Clinical Outcomes After Implantation of Drug Eluting Stents. PMID- 26821691 TI - Event-related potentials reveal early attention bias for negative, unexpected behavior. AB - Numerous studies have documented that expectancy-violating (EV) behavior (i.e., behavior that violates existing person impressions) elicits more effortful cognitive processing compared to expectancy-consistent (EC) behavior. Some studies also have shown that this effect is modulated by the valence of behavior, though this finding is inconsistent with some extant models of expectancy processes. The current research investigated whether the valence of EV information affects very rapid attentional processes thought to tag goal-relevant information for more elaborative processing at later stages. Event-related brain potentials (ERPs) were recorded while participants read depictions of behavior that either were consistent with or violated established impressions about fictitious characters. Consistent with predictions, a very early attention related ERP component, the frontal P2, differentiated negative from positive EV behavior but was unaffected by the valence of EC behavior. This effect occurred much earlier in processing than has been demonstrated in prior reports of EV effects on neural response, suggesting that impression formation goals tune attention to information that might signal the need to modify existing impressions. PMID- 26821692 TI - Analysis of causative microorganism in 248 primary hip arthroplasties revised for infection: a study using the NJR dataset. AB - INTRODUCTION: This study aimed to describe the epidemiology of the causative organism in a series of primary hip arthroplasties revised for a diagnosis of periprosthetic joint infection (PJI) in England and Wales. METHODS: Patient data from the National Joint Registry (NJR) was linked to microbiology data held by Public Health England (PHE) which identified a series of 248 primary hip arthroplasties revised for PJI between 2003 and 2014. Definitive cultures, isolated at time of revision surgery, were available for all cases. Total hip arthroplasty (n = 239, 96%) and hip resurfacing (n = 5, 2%) were the most commonly performed primary procedures. A two-stage revision was the most common operative management (n = 174, 70%). RESULTS: 202 (81%) cases were infected with a single genus microorganism and the most commonly implicated genus was Staphylococcus species (70% of all single genus infections). Staphylococcus species were also the most commonly identified microorganism in mixed genus infections (74% of patient's cultures). There was a significant difference in microorganism distribution when comparing uncemented vs cement implant fixation, with a higher incidence of Gram-negative infection observed in the uncemented group (p = 0.048, Chi-square). CONCLUSIONS: Both prophylactic and therapeutic antibiotic regimes should be focused on targeting Staphylococci. PMID- 26821693 TI - The effects of morphine treatment on the NCAM and its signaling in the MLDS of rats. AB - Prolonged exposure to opiates induces a constellation of neuroadaptations, especially in the mesolimbic dopamine system (MLDS), which leads to alteration in the function of motivational circuitry. The neural cell adhesion molecule (NCAM) mediates cell-cell interactions and plays an important role in processes associated with neural plasticity. Moreover, it has been shown that NCAM were related to risk of alcoholism in human populations. Here, coimmunoprecipitation and western blotting were used to investigate whether morphine treatment induced alteration of the expression of NCAM or its signaling level in MLDS. The rats receiving escalating dose of morphine treatment were divided into three groups: morphine 1d, 3d and 5d group, which were injected subcutaneously with morphine hydrochloride for 1 day, 3 days and 5 days, respectively. Twelve hours after the last injection, animals were sacrificed and the tissues of ventral tegmental area (VTA), prefrontal cortex (PFC) and nucleus accumbens (NAc) were punched out to examine the expression of NCAM or its signaling level. The results showed that morphine treatment had no significant effect on the expression of NCAM, but downregulated the phosphorylation of NCAM-associated focal adhesion kinase (FAK) in the VTA and PFC of rats. In the NAc of rats, however, the expression of NCAM and its signaling were not altered significantly by morphine treatment. These results indicated that the downregulation of NCAM signaling in the VTA and PFC might be involved in the formation of morphine addiction. PMID- 26821694 TI - Towards highly efficient red thermally activated delayed fluorescence materials by the control of intra-molecular pi-pi stacking interactions. AB - Thermally activated delayed fluorescence (TADF) materials have attracted much attention as they can achieve 100% theoretical internal quantum efficiency without using expensive noble metals. However, efficient red TADF emitters are hard to realize according to the energy gap law. Here, three donor-acceptor-donor type TADF emitters with the same acceptor of o-phthalodinitrile (PN) but different donors (9, 9-dimethyl-9, 10-dihydroacridine (DMAC), phenoxazine (PXZ), and phenothiazine (PTZ) for DMAC-PN, PXZ-PN, and PTZ-PN, respectively) have been synthesized, and it is observed that the performance of the emitters can be improved by reducing the intra-molecular pi-pi stacking. DMAC-PN with reduced intra-molecular pi-pi stacking shows a photoluminescence quantum yield (PLQY) of 20.2% in degassed toluene solution, much higher than those of PXZ-PN, and PTZ-PN (0.8%, 0.2%, respectively). An organic light-emitting diode (OLED) employing DMAC PN doped into 4,4'-bis(9H-carbazol-9-yl)biphenyl (CBP) as the emitting layer exhibits a maximum external quantum efficiency (EQE) of 10.2% with the emission peak at 564 nm. Moreover, when DMAC-PN is doped into a polar host, bis[2 (diphenylphosphino)phenyl] ether oxide (DPEPO), the OLED shows a large redshift of the emission maximum to 594 nm, while maintaining a peak EQE as high as 7.2%, indicating that efficient red TADF OLEDs can be fabricated by doping orange TADF emitters into hosts with proper polarity. PMID- 26821695 TI - Clinical diagnostic tools for screening of perioperative stroke in general surgery: a systematic review. AB - Perioperative stroke is a devastating complication that carries high mortality and functional disability. Unfortunately, residual anaesthesia and analgesia may obscure important warning signs and may lead to a delay in the assessment and treatment of major stroke after surgery. The purpose of this review is to examine the utility of existing stroke scales, for the recognition of perioperative stroke in the general surgical population. A total of 21 stroke scales have been described in the literature. Diagnostic performance was reported in 17 scales. The majority of the stroke scales were designed to evaluate current neurological deficits after an established stroke event. Recent abbreviated stroke test, such as the Face, Arm, Speech Test (FAST), were developed to facilitate stroke identification in the emergency department. Only two stroke scales have been applied in the perioperative setting after cardiac, carotid and neurological surgeries. The modified National Institutes of Health Stroke Scale appears to be useful in detecting new subtle neurological deficits in critical care, or high dependency units after surgery. However, in the general postsurgical wards, given the concern about the workload required, abbreviated stroke tests may be more appropriate for routine regular stroke surveillance. It is hoped that these tests will provide rapid assessment of global neurological function to facilitate timely diagnosis and treatment of perioperative stroke. PMID- 26821696 TI - A randomized trial of the effect of low dose epinephrine infusion in addition to tranexamic acid on blood loss during total hip arthroplasty. AB - BACKGROUND: Total hip arthroplasty (THA) is associated with both intraoperative and postoperative blood loss resulting in anaemia and, in some patients, transfusion of red blood cells. Epinephrine enhances coagulation by several mechanisms. We evaluated the effect of intraoperative low dose infusion of epinephrine on intraoperative and early postoperative blood loss. METHODS: After consent, 106 subjects undergoing THA under spinal anaesthesia were randomly assigned to receive an i.v. infusion of either epinephrine 0.05 ug kg(-1) min(-1) or placebo (saline 0.9%) during the entire surgical procedure. Intraoperative tranexamic acid (TXA) was administered to all subjects. The primary outcome was intraoperative blood loss directly measured by drains and weighing swabs. Secondary outcome was total blood loss at 24 h postoperatively calculated using the Gross formula. RESULTS: Of 106 subjects randomized, 6 were excluded, leaving 100 subjects for analyses. Mean duration of surgery was 58 (21) min. Intraoperative blood loss was 343 (95% CI 300-386) ml in the epinephrine group compared with 385 (353-434) ml in the placebo group, P = 0.228. 24 h blood loss was 902 (800-1004) ml in the epinephrine group compared with 1080 (946-1220) ml in the placebo group, P = 0.038. CONCLUSION: In subjects also receiving TXA, intraoperative low dose epinephrine infusion did not reduce intraoperative blood loss in THA but calculated 24 h blood loss was reduced by 180 ml compared with placebo. Further studies on low dose epinephrine in patients at high risk of significant bleeding are warranted. CLINICAL TRIAL REGISTRATION: NCT 01708642. PMID- 26821697 TI - Cricoid pressure impedes tracheal intubation with the Pentax-AWS Airwayscope(r): a prospective randomized trial. AB - BACKGROUND: It is unclear how cricoid pressure affects tracheal intubation with the Pentax-AWS Airwayscope((r)) (AWS). We conducted a prospective randomized clinical trial in anaesthetized patients. METHODS: Sixty patients were allocated to either the cricoid pressure (CP) group (n=30) or the sham group (n=30). We compared the two groups with regard to intubation time, number of attempts required for insertion of the Intlock blade (disposable blade of the AWS) and tracheal intubation, percentage of glottic opening (POGO) score, and subjective difficulty of both laryngoscopy and passage of a tube through the glottis. RESULTS: Intubation time was significantly longer in the CP group (median 45[IQR40-59] s) than in the sham group (32[28-45] s) (P=0.003, 95% CI for median difference 5-24 s). The number required for insertion of the Intlock blade did not differ between the groups (P=0.08), but the number for tracheal intubation was significantly higher in the CP group (1 attempt in 14 patients, 2 in 7, 3 in 9) than in the sham group (1 attempt in 24 patients, 2 in 6; P=0.002). POGO score did not differ significantly between the groups (P=0.60), nor did the subjective difficulty of laryngoscopy (P=0.06). The visual analogue scale score for passage of a tube through the glottis was significantly higher in the CP group than in the sham group (P<0.001). CONCLUSIONS: Cricoid pressure impedes tracheal intubation using the AWS, and is associated with longer intubation time, which can be attributed to increased difficulty in the passage of a tube through the glottis. CLINICAL TRIAL REGISTRY NUMBER: UMIN000018209. PMID- 26821698 TI - Videolaryngoscopes: do they have role during rapid-sequence induction of anaesthesia? PMID- 26821699 TI - Simulation as a set-up for technical proficiency: can a virtual warm-up improve live fibre-optic intubation? AB - BACKGROUND: Fibre-optic intubation (FOI) is an advanced technical skill, which anaesthesia residents must frequently perform under pressure. In surgical subspecialties, a virtual 'warm-up' has been used to prime a practitioner's skill set immediately before performance of challenging procedures. This study examined whether a virtual warm-up improved the performance of elective live patient FOI by anaesthesia residents. METHODS: Clinical anaesthesia yr 1 and 2 (CA1 and CA2) residents were recruited to perform elective asleep oral FOI. Residents either underwent a 5 min, guided warm-up (using a bronchoscopy simulator) immediately before live FOI on patients with predicted normal airways or performed live FOI on similar patients without the warm-up. Subjects were timed performing FOI (from scope passing teeth to viewing the carina) and were graded on a 45-point skill scale by attending anaesthetists. After a washout period, all subjects were resampled as members of the opposite cohort. Multivariate analysis was performed to control for variations in previous FOI experience of the residents. RESULTS: Thirty-three anaesthesia residents were recruited, of whom 22 were CA1 and 11 were CA2. Virtual warm-up conferred a 37% reduction in time for CA1s (mean 35.8 (SD 3.2) s vs. 57 (SD 3.2) s, P<0.0002) and a 26% decrease for CA2s (mean 23 (SD 1.7) s vs. 31 (SD 1.7) s, P=0.0118). Global skill score increased with warm-up by 4.8 points for CA1s (mean 32.8 (SD 1.2) vs. 37.6 (SD 1.2), P=0.0079) and 5.1 points for CA2s (37.7 (SD 1.1) vs. 42.8 (SD 1.1), P=0.0125). Crossover period and sequence did not show a statistically significant association with performance. CONCLUSIONS: Virtual warm-up significantly improved performance by residents of FOI in live patients with normal airway anatomy, as measured both by speed and by a scaled evaluation of skills. PMID- 26821701 TI - Electron transport mechanism of bathocuproine exciton blocking layer in organic photovoltaics. AB - Efficient exciton management is a key issue to improve the power conversion efficiency of organic photovoltaics (OPVs). It is well known that the insertion of an exciton blocking layer (ExBL) having a large band gap promotes the efficient dissociation of photogenerated excitons at the donor-acceptor interface. However, the large band gap induces an energy barrier which disrupts the charge transport. Therefore, building an adequate strategy based on the knowledge of the true charge transport mechanism is necessary. In this study, the true electron transport mechanism of a bathocuproine (BCP) ExBL in OPVs is comprehensively investigated by in situ ultraviolet photoemission spectroscopy, inverse photoemission spectroscopy, density functional theory calculation, and impedance spectroscopy. The chemical interaction between deposited Al and BCP induces new states within the band gap of BCP, so that electrons can transport through these new energy levels. Localized trap states are also formed upon the Al-BCP interaction. The activation energy of these traps is estimated with temperature-dependent conductance measurements to be 0.20 eV. The Al-BCP interaction induces both transport and trap levels in the energy gap of BCP and their interplay results in the electron transport observed. PMID- 26821700 TI - Community pharmacists' experiences in mental illness and addictions care: a qualitative study. AB - BACKGROUND: Community pharmacists are accessible health care professionals who encounter people with lived experience of mental illness and addictions in daily practice. Although some existing research supports that community pharmacists' interventions result in improved patient mental health outcomes, gaps in knowledge regarding the pharmacists' experiences with service provision to this population remain. Improving knowledge regarding the pharmacists' experiences with mental illness and addictions service provision can facilitate a better understanding of their perspectives and be used to inform the development and implementation of interventions delivered by community pharmacists for people with lived experience of mental illness and addictions in communities. METHODS: We conducted a qualitative study using a directed content analysis and the Theoretical Domains Framework as part of our underlying theory of behaviour change and our analytic framework for theme development. The Theoretical Domains Framework facilitates understanding of behaviours of health care professionals and implementation challenges and opportunities for interventions in health care. Thematic analysis co-occurred throughout the process of the directed content analysis. We recruited community pharmacists, with experience dispensing psychotropics, at a minimum, through multiple mechanisms (e.g., professional associations) in a convenience sampling approach. Potential participants were offered the option of focus groups or interviews. RESULTS: Data were collected from one focus group and two interviews involving six pharmacists. Theoretical Domains Framework coding was primarily weighted in two domains: social/professional role and identity and environmental context and resources. We identified five main themes in the experiences of pharmacists in mental illness and addictions care: competing interests, demands, and time; relationships, rapport, and trust; stigma; collaboration and triage; and role expectations and clarity. CONCLUSIONS: Pharmacists are not practicing to their full scope of practice in mental illness and addictions care for several reasons including limitations within the work environment and lack of structures and processes in place to be fully engaged as health care professionals. More research and policy work are needed to examine better integration of pharmacists as members of the mental health care team in communities. PMID- 26821703 TI - The SQM/COSMO filter: reliable native pose identification based on the quantum mechanical description of protein-ligand interactions and implicit COSMO solvation. AB - Current virtual screening tools are fast, but reliable scoring is elusive. Here, we present the 'SQM/COSMO filter', a novel scoring function featuring a quantitative semiempirical quantum mechanical (SQM) description of all types of noncovalent interactions coupled with implicit COSMO solvation. We show unequivocally that it outperforms eight widely used scoring functions. The accuracy and chemical generality of the SQM/COSMO filter make it a perfect tool for late stages of virtual screening. PMID- 26821702 TI - Hybrid phase ligation for efficient synthesis of histone proteins. AB - We introduce a hybrid solid-solution phase ligation approach that combines the efficiency of solid phase ligation with solution phase ligation in the total synthesis of modified histone proteins. A two linker strategy allows analysis throughout work on the solid phase and maximizes yields through cleavage at an external Rink, while an internal HMBA linker allows the native carboxyl terminus for any protein sequence. We demonstrate this approach for two histone proteins: triple-acetylated H4-K5ac, K12ac, K91ac and CENP-A-K124ac. PMID- 26821705 TI - Gastrointestinal helminths of wild hogs and their potential livestock and public health significance in Jamaica. AB - An investigation into the potential for transmission of gastrointestinal helminths from wild hogs to livestock and humans was prompted by concerns of recreational wild-hog hunting in the Caribbean region and the recent practice, by livestock farmers in Jamaica, of co-rearing wild and domesticated swine. Thirty one wild hogs from the Hellshire Hills, a dry limestone forest in southern Jamaica, were necropsied during the period June 2004 to August 2006. Thirteen of the captured animals were male and 18 female. Four species of adult helminths were recovered from the gastrointestinal tracts of the wild hogs: Hyostrongylus rubidus (77%), Globocephalus urosubulatus (48%), Oesophagostomum dentatum (42%) and Macroacanthorhynchus hirudinaceus (77%). Two (6.2%), ten (32.2%) and 18 (58.0%) hogs harboured one, two and three species of helminths, respectively. Mean infection intensities varied from 8.1 for M. hirudinaceus, to 115.5 for O. dentatum. There was no association between any of the recovered helminths and sex of the host; however, a multivariate analysis indicated a positive association between the prevalence of G. urosubulatus and host age (odds ratio (OR) = 6.517). Domesticated hogs co-reared with wild hogs are potentially at risk of infection with all four helminths, while wild-hog hunters and pig farmers may be exposed to M. hirudinaceus. PMID- 26821707 TI - Morphology and molecular analysis of Paratylenchus nanjingensis n. sp. (Nematoda: Paratylenchinae) from the rhizosphere soil of Pinus massoniana in China. AB - Paratylenchus nanjingensis n. sp. was obtained from Nanjing, Jiangsu Province, China. This new species is characterized by having a female with a slender, vermiform body (243-279 MUm), head with distinct submedian lobes, slender and long stylet (64-68 MUm), anchor-shaped stylet knobs, excretory pore anterior to the level of the stylet knobs, small lateral vulval flaps and lateral field with four lines; and male with more distinct body annuli, stylet lacking and pharynx degenerate. The internal transcribed spacer sequences of ribosomal RNA (ITS rRNA) gene of the new species were amplified and sequenced in this study. The phylogenetic relationships of the new species with other Paratylenchus species using the ITS rRNA gene sequences are given. PMID- 26821706 TI - The intestinal helminth community of the spiny-tailed lizard Darevskia rudis (Squamata, Lacertidae) from northern Turkey. AB - Populations of the lizard Darevskia rudis (Bedriaga, 1886) from northern Anatolia were examined for intestinal parasites in adult specimens. One cestode, Nematotaenia tarentolae Lopez-Neyra, 1944 and four nematode species, Spauligodon saxicolae Sharpilo, 1962, Skrjabinelazia hoffmanni Li, 1934, Oswaldocruzia filiformis (Goeze, 1782) and Strongyloides darevskyi Sharpilo, 1976, were found. Three of these nematodes, S. saxicolae, S. hoffmanni and S. darevskyi are suggested to be part of a module in the network of Darevskia spp. and their parasites. Only one, S. darevskyi, was identified as a Darevskia spp. specialist. The very low infection and diversity parameters are indicative of the depauperate helminth communities found in this lacertid lizard, falling among the lowest within the Palaearctic saurians. Nevertheless these values are higher than those found in parthenogenetic Darevskia spp. Interpopulation variation in the intensity of S. saxicolae and N. tarentolae is attributable to local changes in ecological conditions. On the other hand, parasite abundance and richness increased in the warmer localities, while the effect of lizard sex and size on infection was negligible. The structure of these helminth communities in D. rudis are compared with those observed in other European lacertid lizards. PMID- 26821708 TI - The significance of the tail projections in female entomopathogenic nematodes within the family Steinernematidae. AB - Several taxonomic studies of the entomopathogenic nematode family Steinernematidae have reported on the minute tail projections on the tail tips of females of the first generation; however, the occurrence and morphology of these traits in other steinernematid species and their taxonomic significance are still unclear. In the present study, the tail projections in females of seven steinernematid species belonging to four phylogenetic clades were examined. The projections are present in all of the tested species and their number and shape is consistent within species but significantly differs among species. It thus seems that these structures may have taxonomic significance at the species level. Based on these results, we suggest that every description of a new species in the family Steinernematidae should contain a precise morphology of the female tail, focused on these projections, using both light and scanning electron microscopy. PMID- 26821709 TI - Concurrent malaria and arbovirus infections in Kedougou, southeastern Senegal. AB - BACKGROUND: Malaria is one of the leading causes of acute febrile illness (AFI) in Africa. With the advent of malaria rapid diagnostic tests, misdiagnosis and co morbidity with other diseases has been highlighted by an increasing number of studies. Although arboviral infections and malaria are both vector-borne diseases and often have an overlapping geographic distribution in sub-Saharan Africa, information about their incidence rates and concurrent infections is scarce. METHODS: From July 2009 to March 2013 patients from seven healthcare facilities of the Kedougou region presenting with AFI were enrolled and tested for malaria and arboviral infections, i.e., yellow fever (YFV), West Nile (WNV), dengue (DENV), chikungunya (CHIKV), Crimean Congo haemorrhagic fever (CCHFV), Zika (ZIKV), and Rift Valley fever viruses (RVFV). Malaria parasite infections were investigated using thick blood smear (TBS) and rapid diagnostics tests (RDT) while arbovirus infections were tested by IgM antibody detection (ELISA) and RT PCR assays. Data analysis of single or concurrent malaria and arbovirus was performed using R software. RESULTS: A total of 13,845 patients, including 7387 with malaria and 41 with acute arbovirus infections (12 YFV, nine ZIKV, 16 CHIKV, three DENV, and one RVFV) were enrolled. Among the arbovirus-infected patients, 48.7% (20/41) were co-infected with malaria parasites at the following frequencies: CHIKV 18.7% (3/16), YFV 58.3% (7/12), ZIKV 88.9% (8/9), DENV 33.3% (1/3), and RVF 100% (1/1). Fever >=40 degrees C was the only sign or symptom significantly associated with dual malaria parasite/arbovirus infection. CONCLUSIONS: Concurrent malaria parasite and arbovirus infections were detected in the Kedougou region from 2009 to 2013 and need to be further documented, including among asymptomatic individuals, to assess its epidemiological and clinical impact. PMID- 26821710 TI - Effects of Mecp2 loss of function in embryonic cortical neurons: a bioinformatics strategy to sort out non-neuronal cells variability from transcriptome profiling. AB - BACKGROUND: Mecp2 null mice model Rett syndrome (RTT) a human neurological disorder affecting females after apparent normal pre- and peri-natal developmental periods. Neuroanatomical studies in cerebral cortex of RTT mouse models revealed delayed maturation of neuronal morphology and autonomous as well as non-cell autonomous reduction in dendritic complexity of postnatal cortical neurons. However, both morphometric parameters and high-resolution expression profile of cortical neurons at embryonic developmental stage have not yet been studied. Here we address these topics by using embryonic neuronal primary cultures from Mecp2 loss of function mouse model. RESULTS: We show that embryonic primary cortical neurons of Mecp2 null mice display reduced neurite complexity possibly reflecting transcriptional changes. We used RNA-sequencing coupled with a bioinformatics comparative approach to identify and remove the contribution of variable and hard to quantify non-neuronal brain cells present in our in vitro cell cultures. CONCLUSIONS: Our results support the need to investigate both Mecp2 morphological as well as molecular effect in neurons since prenatal developmental stage, long time before onset of Rett symptoms. PMID- 26821712 TI - An HIV Testing Intervention in African American Churches: Pilot Study Findings. PMID- 26821711 TI - Phase I trial of panobinostat and fractionated stereotactic re-irradiation therapy for recurrent high grade gliomas. AB - Panobinostat is an oral HDAC inhibitor with radiosensitizing activity. We investigated the safety, tolerability and preliminary efficacy of panobinostat combined with fractionated stereotactic re-irradiation therapy (FSRT) for recurrent high grade gliomas. Patients with recurrent high grade gliomas were enrolled in a 3 + 3 dose escalation study to determine dose limiting toxicities (DLTs), maximum tolerated dose (MTD), safety, tolerability, and preliminary efficacy. FSRT was prescribed to 30-35 Gy delivered in 10 fractions. Panobinostat was administrated concurrently with radiotherapy. Of 12 evaluable patients, 8 had recurrent GBM, and 4 had recurrent anaplastic astrocytoma. There were three grade 3 or higher toxicities in each the 10 and 30 mg cohorts. In the 30 mg cohort, there was one DLT; grade 4 neutropenia. One patient developed late grade 3 radionecrosis. The median follow up was 18.8 months. The PFS6 was 67, 33, and 83 % for 10, 20, and 30 mg cohorts, respectively. The median OS was 7.8, 6.1 and 16.1 months for the 10, 20 and 30 mg cohorts, respectively. Panobinostat administrated with FSRT is well tolerated at 30 mg. A phase II trial is warranted to assess the efficacy of panobinostat plus FSRT for recurrent glioma. PMID- 26821713 TI - Focus on clinical neuroscience. PMID- 26821714 TI - How could biomarkers of ARDS and AKI drive clinical strategies? PMID- 26821715 TI - Case report: Subjective loss of performance after pulmonary embolism in an athlete- beyond normal values. AB - BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease. For patients with operable CTEPH, there is a clear recommendation for surgical removal of persistent thrombi by pulmonary endarterectomy (PEA). However, without the presence of PH, therapeutic management of chronic thromboembolic disease (CTED) is challenging - especially in highly trained subjects exceeding predicted values of maximal exercise capacity. CASE PRESENTATION: A 43-year-old male athlete reported with progressive exercise limitation since 8 months. Six months earlier, pulmonary embolism had occurred, and was treated since with oral anticoagulation. A pulmonary ventilation/perfusion scan showed severe ventilation/perfusion mismatch: chest CT and pulmonary angiography revealed bilateral wall-adherent thrombotic material, but pulmonary hemodynamics were completely normal. His peak oxygen uptake exceeded predicted values, however exercise ventilatory efficiency was abnormal, compared to a matching athlete. After thoroughly discussing therapeutic options with the patient, he successfully underwent pulmonary endarterectomy at an expert center. Five and twelve months after surgery, his maximal exercise capacity and ventilatory efficiency profoundly improved beyond preoperative values, and his subjective exercise tolerance had returned to normal. CONCLUSIONS: Significant CTED may be present without relevant pathologic changes in pulmonary hemodynamics at rest. Reaching normal values of maximal exercise capacity does not exclude pulmonary vascular disease in highly trained subjects. More data are needed to evaluate the risk-/benefit ratio of PEA in patients with CTED and normal pulmonary hemodynamics. A thorough discussion with the patient as well as shared decision making regarding therapy are mandatory. Cardiopulmonary exercise testing may add important clinical information in the non-invasive diagnostic evaluation at baseline and during follow-up. PMID- 26821716 TI - Maternal near misses from two referral hospitals in Uganda: a prospective cohort study on incidence, determinants and prognostic factors. AB - BACKGROUND: Maternal near misses occur more often than maternal deaths and could enable more comprehensive analysis of risk factors, short-term outcomes and prognostic factors of complications during pregnancy and childbirth. The study determined the incidence, determinants and prognostic factors of severe maternal outcomes (near miss or maternal death) in two referral hospitals in Uganda. METHODS: A prospective cohort study was conducted between March 1, 2013 and February 28, 2014, where cases of severe pregnancy and childbirth complications were included. The clinical conditions included abortion-related complications, obstetric haemorrhage, hypertensive disorders, obstructed labour, infection and pregnancy-specific complications such as febrile illness, anemia and premature rupture of membranes. Near miss cases were defined according to the WHO criteria. Multivariate logistic regression analysis was conducted to identify prognostic factors for severe maternal outcomes. RESULTS: Of 3100 women with severe obstetric complications, 130 (4.2%) were maternal deaths and 695 (22.7%) were near miss cases. Severe pre-eclampsia was the commonest morbidity (incidence ratio (IR) 7.0%, case-fatality rate (CFR) 2.3%), followed by postpartum haemorrhage (IR 6.7%, CFR 7.2%). Uterine rupture (IR 5.5%) caused the highest CFR (17.9%), followed by eclampsia (IR 0.4%, CFR 17.8%). The three groups (maternal deaths, near misses and non-life-threatening obstetric complications) differed significantly regarding gravidity and education level. The commonest diagnostic criteria for maternal near miss were admission to the high dependency unit (HDU) or to the intensive care unit (ICU). Thrombocytopenia, circulatory collapse, referral to a more specialized unit, intubation unrelated to anaesthesia, and cardiopulmonary resuscitation were predictive of maternal death (p < 0.05). Gravidity (ARR 1.4, 95% C1 1.0-1.2); elevated serum lactate levels (ARR 4.5, 95% CI 2.3-8.7); intubation for conditions unrelated to general anaesthesia (ARR 2.6 (95% CI 1.2-5.7), cardiovascular collapse (ARR 4.9, 95% CI 2.5-9.5); transfusion of 4 or more units of blood (ARR 1.9, 95% CI 1.1-3.1); being an emergency referral (ARR 2.6, 95% CI 1.2-5.6); and need for cardiopulmonary resuscitation (ARR 6.1, 95% CI 3.2-11.7), were prognostic factors. CONCLUSIONS: The analysis of near misses is a useful tool in the investigation of severe maternal morbidity. The prognostic factors for maternal death, if instituted, might save many women with obstetric complications. PMID- 26821717 TI - A geriatric assessment in general practice: prevalence, location, impact and doctor-patient perceptions of pain. AB - BACKGROUND: To investigate what a geriatric assessment in general practice adds towards previous findings of prevalence, location, impact and the dyadic doctor patient perception of pain in this age group. METHODS: Cross-sectional study. Consecutive patients aged 70 and over underwent a comprehensive geriatric assessment in general practice that included a basic pain assessment (severity, sites and impact). Patients with pain and their doctors then independently rated its importance. Pain was correlated with further findings from the assessment, such as overall health, physical impairments, everyday function, falls, mood, health related lifestyle, social circumstances, using bivariate and multivariate statistics. Patient-doctor agreement on the importance of pain was calculated using kappa statistics. RESULTS: 219 out of 297 patients (73.7 %) reported pain at any location. Pain was generally located at multiple sites. It was most often present at the knee (33.9%), the lumbar spine (33.5%) as well as the hip (13.8%) and correlated with specific impairments such as restrictions of daily living (knee) or sleep problems (spine). Patients with pain and their physicians poorly agreed on the importance of the pain problem. CONCLUSIONS: A basic pain assessment can identify older patients with pain in general practice. It has resulted in a high prevalence exceeding that determined by encounters in consultations. It has been shown that a geriatric assessment provides an opportunity to address pain in a way that is adapted to older patients' needs - addressing all sites, its specific impact on life, and the patients' perceived importance of pain. Since there is little doctor-patient agreement, this seems a valuable strategy to optimize concrete treatment decisions and patient centered care. TRIAL REGISTRATION: This study is registered in the German Clinical Trial Register ( DRKS00000792 ). PMID- 26821718 TI - Identification, expression, and functional analysis of CLE genes in radish (Raphanus sativus L.) storage root. AB - BACKGROUND: Radish (Raphanus sativus L.) is a widespread agricultural plant forming storage root due to extensive secondary growth which involves cambium proliferation and differentiation of secondary conductive tissues. Closely related to the model object Arabidopsis thaliana, radish is a suitable model for studying processes of secondary growth and storage root development. CLE peptides are a group of peptide phytohormones which play important role in the regulation of primary meristems such as SAM, RAM, and procambium, as well as secondary meristems. However, the role of CLE peptides in lateral growth of root during storage root formation has not been studied to date. RESULTS: In present work we studied the role of CLE peptides in the development of storage root in radish. We have identified 18 CLE genes of radish (RsCLEs) and measured their expression in various plant organs and also at different stages of root development in R. sativus and Raphanus raphanistrum-its close relative which does not form storage root. We observed significant decline of expression levels for genes RsCLE1, 2, 11, 13, and 16, and also multifold increase of expression levels for genes RsCLE19, and 41 during secondary root growth in R. sativus but not in R. raphanistrum. Expression of RsCLE 2, 19, and 41 in R. sativus root was confined to certain types of tissues while RsCLE1, 11, 13, and 16 expressed throughout the root. Experiments on overexpression of RsCLE2, 19 and 41 or treatment of radish plants with synthetic CLE peptides revealed that CLE19 and CLE2 increase the number of xylem elements, and CLE41 induces the formation of extra cambium foci in secondary xylem. Expression levels of RsCLE2 and 19 strongly decrease in response to exogenous cytokinin, while auxin causes dramatic increase of RsCLE19 expression level and decrease of RsCLE41 expression. CONCLUSIONS: Our data allow us to hypothesize about the role of RsCLE2, 19 and 41 genes in the development of storage root of Raphanus sativus, e.g. RsCLE19 may play a role in auxin-dependent processes of xylem differentiation and RsCLE41 stimulates cambium activity. PMID- 26821721 TI - Systems Of Values And Their Multidimensional Representations. AB - The purposes of the research were: (1) to elicit spontaneously mentioned values from a large and diverse sample of respondents, (2) to compare the spontaneously mentioned values with Rokeach's terminal and instrumental values, (3) to determine the ways in which both sets of values were perceived as varying on selected independently measured properties, and (4) to provide structural representations of both value systems. The spontaneously mentioned values were interpretable in terms of the focus of concern (Self versus Society) and beliefs about how these concerns were to be achieved. The spontaneously mentioned values also revealed a simpler structure than Rokeach's values. The results are discussed in terms of the errors inherent in constraining respondents to a fixed response format and the implications for cross cultural research on the underlying structure of value systems. PMID- 26821720 TI - The kidney and type 2 diabetes mellitus: therapeutic implications of SGLT2 inhibitors. AB - Understanding the role of the kidneys in type 2 diabetes mellitus (T2DM) has taken on an increased importance in recent years with the arrival of sodium glucose co-transporter 2 (SGLT2) inhibitors - antihyperglycemic agents (AHAs) that specifically target the kidneys. This review includes an update on the physiology of the kidneys, their role in the pathophysiology of T2DM, and the mechanisms implicated in the development and progression of diabetic kidney disease, such as glomerular hyperfiltration and inflammation. It also discusses renal issues that could influence the choice of AHA for patients with T2DM, including special populations such as patients with concomitant chronic kidney disease. The most recent data published on the clinical efficacy and safety of the SGLT2 inhibitors canagliflozin, dapagliflozin, and empagliflozin and their effects on renal function are presented, showing how the renally mediated mechanisms of action of these agents translate into clinical benefits, including the potential for renoprotection. The observed positive effects of these agents on measures such as glucose control, estimated glomerular filtration rate, albumin-to-creatinine ratio, blood pressure, and body weight in patients both with and without impaired renal function suggest that SGLT2 inhibitors represent an important extension to the diabetes treatment armamentarium. PMID- 26821722 TI - The Literature On Cluster Analysis. AB - There has been an explosion of interest in cluster analysis since 1960. The "explosion" of this literature is documented through: (a) a rapid growth in the number of articles which have been published using this technique; (b) the wide range of sciences interested in clustering; (c) the large and growing number of software programs for performing cluster analysis; (d) the formation of cliques of cluster analysis users; and (e) the resulting fragmentation of terminology into jargon which restricts interdisciplinary communication. In response to the effects of this explosion, it is expected that the future literature on clustering will contain a number of attempts at consolidation. Nevertheless, the facts that cluster analysis has no scientific home, that clustering methods are not based upon a well-enunciated statistical theory and that cluster analysis is tied to the complex topic of classification means that the consolidation of this literature will be difficult. PMID- 26821723 TI - Factor Analysis Of Genetic And Environmental Correlation Matrices. AB - Several researchers have recently attempted to apply factor analytic procedures to genetic data. These attempts, however, have been unsystematic. The application of component analysis to phenotypic, genetic and environmental correlation matrices is discussed in this paper. Formulas for computing phenotypic, genetic and environmental component scores are given. The interpretation of factors is discussed and a worked example is included. PMID- 26821719 TI - Post-thaw ATP supplementation enhances cryoprotective effect of iodixanol in rat spermatozoa. AB - BACKGROUND: Successful cryopreservation of rat spermatozoa from various strains still remains a challenge. The objective of this study was to determine if combinations of OptiPrepTM (iodixanol) and adenosine 5'-triphosphate (ATP) can improve rat sperm function during the cryopreservation procedure. METHODS: Epididymal rat spermatozoa were frozen under different OptiPrepTM concentrations (0, 1, 2, 3 or 4 %) and were diluted with media supplemented with or without 2 mM ATP after thawing. Post-thaw sperm motility, acrosomal membrane integrity (AMI) and mitochondrial membrane potential (MMP) were then evaluated. In addition, the effect of different OptiPrepTM concentrations on fresh and cooled rat spermatozoa was tested via motility. RESULTS: There was no effect of OptiPrepTM on motility of fresh and cooled spermatozoa. The supplementation of 1 and 2 % OptiPrepTM increased motility of frozen spermatozoa at 10 min after thawing, while it did not improve motility of spermatozoa at 3 h after thawing in the absence of ATP. During incubation of thawed spermatozoa, the ATP addition protected time dependent decrease in motility after thawing in OptiPrepTM-treated samples. OptiPrepTM had no effect on AMI and MMP in frozen-thawed spermatozoa but combinations of OptiPrepTM and ATP improved MMP in frozen-thawed spermatozoa. CONCLUSIONS: Iodixanol has cryoprotective effects during rat sperm freezing without any toxic effect. Moreover, the combinations of iodixanol and ATP have a beneficial role in maintaining function of frozen-thawed rat spermatozoa for long period of incubation post-thaw. PMID- 26821724 TI - Some Checking Procedures For Extension Analysis. AB - The extension procedure in common factor analysis is a two-stage least squares estimation procedure which may yield very poor fit to the extension variables and may yield Heywood cases. The three residual matrices, and three measures of goodness of fit that arise from the procedure should be examined in most applications, and the possible presence of Heywood variables in the extension set should be considered. PMID- 26821725 TI - Achievement Motive: A Faceted Definition And Structural Analysis. AB - Facet technique is used to analyze contents of achievement motive questionnaire items proposed in recent years and to construct an explicit definition for achievement motive. The theoretical discussion provides the rationale for an hypothesis concerning the structure (i.e. classifications, ordering, dimensionality) of interrelationships among components of achievement motive. Using data from a sample of executive managers, the hypothesis is then tested by means of Guttman's Smallest Space Analysis and found to be correct. PMID- 26821726 TI - Analysis Of Repeated Measures Data: A Simulation Study. AB - This paper examines three statistical analysis procedures appropriate to repeated measures data -- classical mixed model analysis of variance, multivariate analysis of repeated measures, and analysis of covariance structures. These procedures differ in their assumptions concerning the covariances between the latent random variables in the model underlying the repeated measures. Simulated data were employed to investigate the effect that violating the assumptions of each model had on the following: Type I error rates; power of the test; degree of bias in the parameter estimates; and the relative efficiency of the estimates. The data indicate that with respect to Type I error rates and estimates of repeated measures effects, violations of assumptions for all three procedures produce similar results. Depending on the size of the repeated measures effects, there are differences between procedures concerning power. The estimates produced by analysis of covariance structures techniques tend to have smaller standard errors. PMID- 26821727 TI - A Multidimensional Scaling Study Of Person Perception In Children. AB - Anglo and Black children at two age levels and of both sexes judged the similarity of twelve stimulus persons, using a proximity setting technique. The stimuli consisted of cardboard caricatures of individuals representing the roles of policemen, male and female teachers, parents, male and female peers, and self. Where appropriate, stimuli of both Black and Anglo races were present. The judgments were used as inputs for an individual difference multidimensional scaling program. The resultant dimensions of social perception were interpreted as racial identification, sex, and age. Some differences in perception between subjects were obtained. Implications of the present investigation for future research were discussed. PMID- 26821728 TI - A New Perspective On Sequential Testing Procedures In Canonical Analysis: A Monte Carlo Evaluation. AB - A Monte Carlo study was conducted in order to compare four testing procedures in establishing the number of nonzero population roots in a canonical analysis. Three of the methods investigated were sequential testing methods which have lately fallen under heavy criticism. The fourth method was a test advocated by Harris (1976) to be a more appropriate test. Results demonstrated the effectiveness of the sequential testing procedures and the relative ineffectiveness of the Harris method. The conclusion was that the criticisms aimed at the sequential testing for nonzero roots in canonical analysis are simply not well-founded. PMID- 26821729 TI - Size fractionation of waste-to-energy boiler ash enables separation of a coarse fraction with low dioxin concentrations. AB - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) formed in modern Waste-to-Energy plants are primarily found in the generated ashes and air pollution control residues, which are usually disposed of as hazardous waste. The objective of this study was to explore the occurrence of PCDD/F in different grain size fractions in the boiler ash, i.e. ash originating from the convection pass of the boiler. If a correlation between particle size and dioxin concentrations could be found, size fractionation of the ashes could reduce the total amount of hazardous waste. Boiler ash samples from ten sections of a boiler's convective part were collected over three sampling days, sieved into three different size fractions - <0.09 mm, 0.09-0.355 mm, and >0.355 mm - and analysed for PCDD/F. The coarse fraction (>0.355 mm) in the first sections of the horizontal convection pass appeared to be of low toxicity with respect to dioxin content. While the total mass of the coarse fraction in this boiler was relatively small, sieving could reduce the amount of ash containing toxic PCDD/F by around 0.5 kg per tonne input waste or around 15% of the collected boiler ash from the convection pass. The mid-size fraction in this study covered a wide size range (0.09-0.355 mm) and possibly a low toxicity fraction could be identified by splitting this fraction into more narrow size ranges. The ashes exhibited uniform PCDD/F homologue patterns which suggests a stable and continuous generation of PCDD/F. PMID- 26821730 TI - Validation of Warwick-Edinburgh Mental Well-being Scale (WEMWBS) in a population of people using Secondary Care Mental Health Services. AB - BACKGROUND: The Warwick-Edinburgh Mental Well-being Scale (WEMWBS) is a relatively new measure and to date has been validated in a number of populations, including student, general and adolescent samples across the UK. There is increasing interest in measuring the mental well-being of users of secondary care mental health services and therefore it is apt to validate WEMWBS for this population. AIMS: To investigate the validity of WEMWBS in a secondary care mental health service user population. METHOD: Data was collected from two NHS Trusts and one charity. Analyses are based on 1180 completed WEMWBS. RESULTS: WEMWBS scores for this population are significantly lower than those in a general population (Mean 34.9, SD 13.8). Overall the data analyses supported the use of WEMWBS in this population sample. The Rasch analysis found that the majority of the items can be seen as measuring one dimension. The confirmatory factor analysis supports a one factor solution and thus, measures a single underlying concept. CONCLUSIONS: The findings from this study show WEMWBS to be a valid and reliable measure for this population sample. PMID- 26821731 TI - Enhanced in Vitro Mineralization and in Vivo Osteogenesis of Composite Scaffolds through Controlled Surface Grafting of L-Lactic Acid Oligomer on Nanohydroxyapatite. AB - Nanocomposite of hydroxyapatite (HA) surface grafted with L-lactic acid oligomer (LAc oligomer) (op-HA) showed improved interface compatibility, mechanical property, and biocompatibility in our previous study. In this paper, composite scaffolds of op-HA with controlled grafting different amounts of LAc oligomer (1.1, 5.2, and 9.1 wt %) were fabricated and implanted to repair rabbit radius defects. The dispersion of op-HA nanoparticles was more uniform than n-HA in chloroform and nanocomposites scaffold. Calcium and phosphorus exposure, in vitro biomineralization ability, and cell proliferation were much higher in the op HA1.1 wt %/PLGA scaffolds than the other groups. The osteodifferentiation and bone fusion in animal tests were significantly enhanced for op-HA5.2 wt %/PLGA scaffolds. The results indicated that the grafted LAc oligomer of 5.2 or 9.1 wt %, which formed a barrier layer on the HA surface, prevented the exposure of nucleation sites. The shielded nucleation sites of op-HA particles (5.2 wt %) might be easily exposed as the grafted LAc oligomer was decomposed easily by enzyme systems in vivo. Findings from this study have revealed that grafting 1.1 wt % amount of LAc oligomer on hydroxyapatite could improve in vitro mineralization, and 5.2 wt % could promote in vivo osteogenesis capacity of composite scaffolds. PMID- 26821732 TI - Genomics, clinical research, and learning health care systems: Strategies to improve patient care. PMID- 26821733 TI - [Modified purse string suture to reduce the size of surgical defect]. AB - INTRODUCTION: Skin carcinomas require excision with clear margins. In the head and neck region, these excisions most often result in round or oval defects. Due to the big size of the defect and limited tissue elasticity, it is not always possible to close these defects in the same operation. We describe a technique to minimize the size of the defect. TECHNICAL NOTE: It is an improved purse string suture technique. The purse string suture is realized with a circular continuous intradermal suture and is improved by three or four V-Y sutures, in order to reduce the skin defect. DISCUSSION: It is an easy, fast and effective technique for decreasing the size of the skin defect and for speeding up the healing. PMID- 26821734 TI - [Oral Torus or Torii, why?]. PMID- 26821735 TI - Probiotics for treatment and primary prevention of allergic diseases and asthma: looking back and moving forward. AB - Microbial ecosystems cover the surface of the human body and it is becoming increasingly clear that our modern environment has profound effects on microbial composition and diversity. A dysbiotic gut microbiota has been associated with allergic diseases and asthma in cross-sectional and observational studies. In an attempt to restore this dysbiosis, probiotics have been evaluated in randomized controlled trials. Here, we review treatment and primary prevention studies, recent meta-analyses, and discuss the current understanding of the role of probiotics in this context. Many meta-analyses have shown a moderate benefit of probiotics for eczema prevention, whereas there is less evidence of a benefit for other allergic manifestations. Because of very low quality evidence and heterogeneity between studies, specific advice on the most effective regimens cannot yet be given - not even for eczema prevention. To be able to adopt results into specific recommendations, international expert organizations stress the need for well-designed studies. PMID- 26821736 TI - The pre-operative rate of growth of colorectal metastases in patients selected for liver resection does not influence post-operative disease-free survival. AB - AIMS: To assess the potential association between the change in diameter of colorectal liver metastases between pre-operative imaging and liver resection and disease-free survival in patients who do not receive pre-operative liver-directed chemotherapy. MATERIALS AND METHODS: Analysis of a prospectively maintained database of patients undergoing liver resection for colorectal liver metastases between 2005 and 2012 was undertaken. Change in tumour size was assessed by comparing the maximum tumour diameter at radiological diagnosis determined by imaging and the maximum tumour diameter measured at examination of the resected specimen in 157 patients. RESULTS: The median interval from first scan to surgery was 99 days and the median increase in tumour diameter in this interval was 38%, equivalent to a tumour doubling time (DT) of 47 days. Tumour DT prior to liver resection was longer in patients with T1 primary tumours (119 days) than T2-4 tumours (44 days) and shorter in patients undergoing repeat surgery for intra hepatic recurrence (33 days) than before primary resection (49 days). The median disease-free survival of the whole cohort was 1.57 years (0.2-7.3) and multivariate analysis revealed no association between tumour DT prior to surgery and disease-free survival. CONCLUSIONS: The rate of growth of colorectal liver metastases prior to surgery should not be used as a prognostic factor when considering the role of resection. PMID- 26821737 TI - Assessment of inhaled acute ammonia-induced lung injury in rats. AB - This study examined acute toxicity and lung injury following inhalation exposure to ammonia. Male Sprague-Dawley rats (300-350 g) were exposed to 9000, 20,000, 23,000, 26,000, 30,000 or 35,000 ppm of ammonia for 20 min in a custom head-out exposure system. The exposure atmosphere, which attained steady state within 3 min for all ammonia concentrations, was monitored and verified using a Fourier transform infrared spectroscopy (FTIR) gas analyzer. Animals exposed to ammonia resulted in dose-dependent increases in observed signs of intoxication, including increased chewing and licking, ocular irritation, salivation, lacrimation, oronasal secretion and labored breathing. The LCt50 of ammonia within this head out inhalation exposure model was determined by probit analysis to be 23,672 ppm (16,489 mg/m(3)) for the 20 min exposure in male rats. Exposure to 20,000 or 23,000 ppm of ammonia resulted in significant body weight loss 24-h post exposure. Lung edema increased in all ammonia-exposed animal groups and was significant following exposure to 9000 ppm. Bronchoalveolar fluid (BALF) protein concentrations significantly increased following exposure to 20,000 or 23,000 ppm of ammonia in comparison to controls. BAL cell (BALC) death and total cell counts increased in animals exposed to 20,000 or 23,000 ppm of ammonia in comparison to controls. Differential cell counts of white blood cells, neutrophils and platelets from blood and BALF were significantly increased following exposure to 23,000 ppm of ammonia. The following studies describe the validation of a head out inhalation exposure model for the determination of acute ammonia-induced toxicity; this model will be used for the development and evaluation of potential therapies that provide protection against respiratory and systemic toxicological effects. PMID- 26821738 TI - Attachment style as a mediator between childhood maltreatment and the experience of betrayal trauma as an adult. AB - Previous research has demonstrated a positive association between child maltreatment and adult interpersonal trauma (Arata, 2000; Crawford & Wright, 2007). From a betrayal trauma theory perspective, evidence suggests that the experience of trauma high in betrayal (e.g., child maltreatment by parents or guardians) increases ones risk of betrayal trauma as an adult (Gobin & Freyd, 2009). However, the mechanisms explaining these associations are not well understood; attachment theory could provide further insight. Child maltreatment is associated with insecure attachment (Baer & Martinez, 2006; Muller et al., 2000). Insecure attachment is also associated with deficits in interpersonal functioning and risk for intimate partner violence, suggesting insecure attachment may mediate the relationship between child maltreatment and the experience of betrayal trauma as an adult. The current study tested this hypothesis in a sample of 601 college students. Participants completed online questionnaires including the Child Abuse and Trauma Scale (CATS), the Experiences in Close Relationships - Revised (ECR-R) and the Brief Betrayal Trauma Survey (BBTS). Results indicated that child maltreatment is associated with adult betrayal trauma and anxious attachment partially mediates this relationship. PMID- 26821740 TI - Autologous platelet concentrates in head and neck cancer surgery: Are such bio adjuvants really safe? PMID- 26821739 TI - What Do Danish Youth Want to Know About Sex? Twenty Years of Telephone Counseling on Sexual and Reproductive Issues. AB - Young people's need for sexual counseling is well documented, and both website and hotline-based services have been established as means of health promotion in this field. Such measures, however, are rarely evaluated, so this article offers data from the world's presumably oldest sexuality helpline aimed at young people. With an observation time of two decades and a total of 42,325 questions asked, the study provides a unique glance into the sexual landscapes of Danish youth. It shows an overall male predominance among callers and reveals that the counseling themes change over time and differ between both age groups and genders. The article suggests that telephone counseling-although more resource demanding than online alternatives-provides a secure, anonymous, and dialogue-based arena for discussing delicate sexual issues and therefore may constitute a viable supplement to web-based media for young people with the need to talk rather than just chat. PMID- 26821741 TI - Modifying Hofstee standard setting for assessments that vary in difficulty, and to determine boundaries for different levels of achievement. AB - BACKGROUND: Fixed mark grade boundaries for non-linear assessment scales fail to account for variations in assessment difficulty. Where assessment difficulty varies more than ability of successive cohorts or the quality of the teaching, anchoring grade boundaries to median cohort performance should provide an effective method for setting standards. METHODS: This study investigated the use of a modified Hofstee (MH) method for setting unsatisfactory/satisfactory and satisfactory/excellent grade boundaries for multiple choice question-style assessments, adjusted using the cohort median to obviate the effect of subjective judgements and provision of grade quotas. RESULTS: Outcomes for the MH method were compared with formula scoring/correction for guessing (FS/CFG) for 11 assessments, indicating that there were no significant differences between MH and FS/CFG in either the effective unsatisfactory/satisfactory grade boundary or the proportion of unsatisfactory graded candidates (p > 0.05). However the boundary for excellent performance was significantly higher for MH (p < 0.01), and the proportion of candidates returned as excellent was significantly lower (p < 0.01). MH also generated performance profiles and pass marks that were not significantly different from those given by the Ebel method of criterion referenced standard setting. CONCLUSIONS: This supports MH as an objective model for calculating variable grade boundaries, adjusted for test difficulty. Furthermore, it easily creates boundaries for unsatisfactory/satisfactory and satisfactory/excellent performance that are protected against grade inflation. It could be implemented as a stand-alone method of standard setting, or as part of the post-examination analysis of results for assessments for which pre examination criterion-referenced standard setting is employed. PMID- 26821742 TI - RiboGalaxy: A browser based platform for the alignment, analysis and visualization of ribosome profiling data. AB - Ribosome profiling (ribo-seq) is a technique that uses high-throughput sequencing to reveal the exact locations and densities of translating ribosomes at the entire transcriptome level. The technique has become very popular since its inception in 2009. Yet experimentalists who generate ribo-seq data often have to rely on bioinformaticians to process and analyze their data. We present RiboGalaxy ( http://ribogalaxy.ucc.ie ), a freely available Galaxy-based web server for processing and analyzing ribosome profiling data with the visualization functionality provided by GWIPS-viz ( http://gwips.ucc.ie ). RiboGalaxy offers researchers a suite of tools specifically tailored for processing ribo-seq and corresponding mRNA-seq data. Researchers can take advantage of the published workflows which reduce the multi-step alignment process to a minimum of inputs from the user. Users can then explore their own aligned data as custom tracks in GWIPS-viz and compare their ribosome profiles to existing ribo-seq tracks from published studies. In addition, users can assess the quality of their ribo-seq data, determine the strength of the triplet periodicity signal, generate meta-gene ribosome profiles as well as analyze the relative impact of mRNA sequence features on local read density. RiboGalaxy is accompanied by extensive documentation and tips for helping users. In addition we provide a forum ( http://gwips.ucc.ie/Forum ) where we encourage users to post their questions and feedback to improve the overall RiboGalaxy service. PMID- 26821743 TI - Increases of microRNA let-7e in peripheral blood mononuclear cells in Hashimoto's disease. AB - MicroRNA (miRNA) is a family of non-coding RNAs that have important roles in various vital functions. It has been reported that let-7e, a miRNA, may be involved in the regulation of interleukin (IL)-10 production. The purpose of this study was to evaluate the role of let-7e as a regulator of IL-10 production in the pathological processes of autoimmune thyroid diseases (AITDs). We evaluated the association between let-7e expression and intracellular expression of IL-10 in the peripheral blood mononuclear cells (PBMCs) collected from 11 healthy volunteers. Then we investigated the expression levels of let-7e in the PBMCs of 50 patients with Graves' disease (GD), 42 patients with Hashimoto's disease (HD) and 28 healthy controls. We found negative correlations between the expression level of let-7e and IL-10 messengerRNA (mRNA) and between the expression level of let-7e and proportion of IL-10(+) cells in stimulated PBMCs from healthy volunteers (r = -0.44, p = 0.0267 and r = -0.49, p = 0.0166, respectively). The expression levels of let-7e were significantly increased in HD patients compared with those in GD patients and healthy volunteers (p = 0.0003 and p = 0.0011, respectively). let-7e may be associated with the pathogenesis of HD through the regulation of intracellular IL-10 expression. PMID- 26821744 TI - Retiring the central executive. AB - Reasoning, problem solving, comprehension, learning and retrieval, inhibition, switching, updating, or multitasking are often referred to as higher cognition, thought to require control processes or the use of a central executive. However, the concept of an executive controller begs the question of what is controlling the controller and so on, leading to an infinite hierarchy of executives or "homunculi". In what is now a QJEP citation classic, Baddeley [Baddeley, A. D. (1996). Exploring the central executive. Quarterly Journal of Experimental Psychology, 49A, 5-28] referred to the concept of a central executive in cognition as a "conceptual ragbag" that acted as a placeholder umbrella term for aspects of cognition that are complex, were poorly understood at the time, and most likely involve several different cognitive functions working in concert. He suggested that with systematic empirical research, advances in understanding might progress sufficiently to allow the executive concept to be "sacked". This article offers an overview of the 1996 article and of some subsequent systematic research and argues that after two decades of research, there is sufficient advance in understanding to suggest that executive control might arise from the interaction among multiple different functions in cognition that use different, but overlapping, brain networks. The article concludes that the central executive concept might now be offered a dignified retirement. PMID- 26821745 TI - Preliminary in vitro antiplasmodial activity of Aristolochia griffithii and Thalictrum foliolosum DC extracts against malaria parasite Plasmodium falciparum. AB - BACKGROUND: Resistance development in human malaria parasites against commonly used antimalarial drugs has necessitated the scientific exploration of traditionally used antimalarial plants. Plant derivatives have been used for curing malaria historically. The present study involves in vitro evaluation of two medicinally important plants Aristolochia griffithii and Thalictrum foliolosum DC used in antimalarial chemotherapy by the tribes of northeast India. METHOD: Chloroform, ethyl acetate and n-butanol extracts of Aristolochia griffithii and Thalictrum foliolosum DC were evaluated in vitro against chloroquine sensitive (SS) and chloroquine resistance strains (RS) of P. falciparum. The tests were conducted following WHO standard method and the inhibition of parasite (IC50) was calculated. RESULTS: In A. griffithii, the IC50 value for ethyl acetate extracts against SS was 6.2 +/- 0.02 MUg/ml and found to be lower than chloroform extracts, which exhibited an IC50 value of 14.1 +/- 0.1 MUg/ml (t = 191.1; p < 0.0001). The IC50 values of both chloroform and ethyl acetate extracts for RS were higher as compared to the SS (p < 0.0001). In T. foliolosum DC the IC50 concentration of chloroform extracts for SS and RS were 0.5 +/- 0.0 and 1.1 +/- 0.0 MUg/ml respectively (t = 54.2; p < 0.0001). CONCLUSION: The present findings, although preliminary, but scientifically demonstrate that identification and isolation of active compounds of these two plant materials and testing against different Plasmodium species could lead to the development of potential antimalarial drugs for future. PMID- 26821747 TI - [Association between evacuation condition and habitual physical activity in Great East Japan Earthquake evacuees: The Fukushima Health Management Survey]. AB - Objectives: Prevalence of life-style disease has increased dramatically in evacuees due to the Great East Japan Earthquake. One reason may be that physical activity level decreased from life environment changes due to evacuation. However, associations between evacuation condition and habitual physical activity have not been studied. We examined this association in Fukushima residents who participated in the Fukushima Health Management Survey. Methods: In this study, 37,843 evacuees from 13 municipal evacuation zones from the nuclear-power accident caused by the Great East Japan Earthquake, born before April 1, 1995, were included in the analysis. Evacuation condition was defined by disaster living place (13 zones), evacuation place (inside or outside the prefecture), and current living status (evacuation shelter or temporary housing, rental housing/ apartment, and relative's home or own home). Habitual physical activity was defined from self-administered questionnaires as participants who responded "almost every day" and "2-4 times/week" of regular exercise. In the analysis, habitual physical activity prevalence was aggregated by gender and variables (living place in the disaster, evacuation place, and current living status). Prevalence was adjusted for age, disaster living place, evacuation place, and current living status by standard analysis of covariance methods. Results: Adjusted prevalences of habitual physical activity were: men, 27.9-46.5%; women, 27.0-43.7% in each disaster living place. The differences were 18.6% point in men and 16.7% point in women. For evacuation place, physical activity outside the prefecture for men (37.7%) and inside the prefecture for women (32.1%) were higher, but those differences were only 2.2% point and 1.8% point in men and women, respectively. For current living status, physical activity of those in rental housing/ apartment was the lowest; evacuation shelter or temporary housing was the highest in both genders (men: 38.9%, women: 36.7%). Compared with residents in evacuation shelter or temporary housing, those in rental housing/apartment were 5.4% point and 7.1% point lower and those in relative's home or own home were 2.0% point and 4.2% point lower in men and women. Conclusion: Habitual physical activity in residents who lived in 13 municipal evacuation zone differed by disaster living place and current living status, while it was similar regardless of placement in the prefecture. In particular, prevalence was the lowest in participants who lived in rental housing/ apartment. We need to plan and perform additional life-style disease prevention strategies for participants who become isolated. PMID- 26821748 TI - [Implementation and Evaluation of Infection Control Seminars for Care and Welfare Facilities]. PMID- 26821749 TI - [Relationship between time elapsed since a large earthquake and its impact on disease occurrence: Summary table of earthquake disaster epidemiologic studies]. PMID- 26821746 TI - Long non-coding RNAs display higher natural expression variation than protein coding genes in healthy humans. AB - BACKGROUND: Long non-coding RNAs (lncRNAs) are increasingly implicated as gene regulators and may ultimately be more numerous than protein-coding genes in the human genome. Despite large numbers of reported lncRNAs, reference annotations are likely incomplete due to their lower and tighter tissue-specific expression compared to mRNAs. An unexplored factor potentially confounding lncRNA identification is inter-individual expression variability. Here, we characterize lncRNA natural expression variability in human primary granulocytes. RESULTS: We annotate granulocyte lncRNAs and mRNAs in RNA-seq data from 10 healthy individuals, identifying multiple lncRNAs absent from reference annotations, and use this to investigate three known features (higher tissue-specificity, lower expression, and reduced splicing efficiency) of lncRNAs relative to mRNAs. Expression variability was examined in seven individuals sampled three times at 1 or more than 1-month intervals. We show that lncRNAs display significantly more inter-individual expression variability compared to mRNAs. We confirm this finding in two independent human datasets by analyzing multiple tissues from the GTEx project and lymphoblastoid cell lines from the GEUVADIS project. Using the latter dataset we also show that including more human donors into the transcriptome annotation pipeline allows identification of an increasing number of lncRNAs, but minimally affects mRNA gene number. CONCLUSIONS: A comprehensive annotation of lncRNAs is known to require an approach that is sensitive to low and tight tissue-specific expression. Here we show that increased inter individual expression variability is an additional general lncRNA feature to consider when creating a comprehensive annotation of human lncRNAs or proposing their use as prognostic or disease markers. PMID- 26821750 TI - [Collaboration between public health nurses and the private sector]. AB - OBJECTIVES: We clarified collaborations between public health nurses (PHNs) and the private sector, such as nonprofit organizations. METHODS: Semi-structured interviews were conducted with 11 private sector organizations and 13 PHNs who collaborate with them between December 2012 to October 2013. Interview guides were: overall suicide preventive measurements, details of collaboration between private sector organizations and PHNs, and suicide prevention outcomes/issues. Data from private sector organizations and PHNs were separately analyzed and categories created using qualitative and inductive design. Private sector organizations' and PHNs' categories were compared and separated into core categories by similarities. RESULTS: Six categories were created: 1. establishing a base of mutual understanding; 2. raising public awareness of each aim/characteristic; 3. competently helping high suicidal risk persons detected during each activity; 4. guarding lives and rehabilitating livelihoods after intervention; 5. restoring suicide attempters/bereaved met in each activity; and 6. continuing/expanding activities with reciprocal cohesion/evaluation. CONCLUSION: PHNs are required to have the following suicide prevention tasks when collaborating with private sector organizations: understanding the private sector civilization, sharing PHN experiences, improving social determinants of health, meeting basic needs, supporting foundation/difficulties each other (Dear editor. Thank you for kind comments. I was going to explain that PHNs and NPOs support each other their foundation of activity and difficulties in their activities. The foundations include knowledge, information, budgets, manpower etc. The difficulties mean like suffering faced with suicide during activities.), and enhancing local governments' flexibilities/ promptness. PMID- 26821751 TI - Ground state potential energy surfaces around selected atoms from resonant inelastic x-ray scattering. AB - Thermally driven chemistry as well as materials' functionality are determined by the potential energy surface of a systems electronic ground state. This makes the potential energy surface a central and powerful concept in physics, chemistry and materials science. However, direct experimental access to the potential energy surface locally around atomic centers and to its long-range structure are lacking. Here we demonstrate how sub-natural linewidth resonant inelastic soft x ray scattering at vibrational resolution is utilized to determine ground state potential energy surfaces locally and detect long-range changes of the potentials that are driven by local modifications. We show how the general concept is applicable not only to small isolated molecules such as O2 but also to strongly interacting systems such as the hydrogen bond network in liquid water. The weak perturbation to the potential energy surface through hydrogen bonding is observed as a trend towards softening of the ground state potential around the coordinating atom. The instrumental developments in high resolution resonant inelastic soft x-ray scattering are currently accelerating and will enable broad application of the presented approach. With this multidimensional potential energy surfaces that characterize collective phenomena such as (bio)molecular function or high-temperature superconductivity will become accessible in near future. PMID- 26821752 TI - WISP1 mediates hepatic warm ischemia reperfusion injury via TLR4 signaling in mice. AB - Wnt-induced secreted protein-1 (WISP1) is an extracellular matrix protein that has been reported in cancer researches. Our previous studies on WISP1 implied it could be a harmful mediator in septic mice. However, its role in liver ischemia reperfusion (I/R) injury is unknown. This study investigated the effects of WISP1 on liver I/R damage. Male C57BL/6 wild-type mice were used to undergo 60 min segmental (70%) ischemia. WISP1 expression was measured after indicated time points of reperfusion. Anti-WISP1 antibody was injected intraperitoneally to mice. Toll-like receptor 4 (TLR4) knockout mice and TIR-domain-containing adaptor inducing interferon-beta (TRIF) knockout mice were adopted in this study. WISP1 was significantly enhanced after 6 h of reperfusion when compared with sham treated mice and significantly decreased either by TLR4 knockout mice or TRIF knockout mice. Anti-WISP1 antibody significantly decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), pathological changes and pro-inflammatory cytokine levels in the mice following I/R. Furthermore, significantly increased serum transaminase levels were found in C57 wild-type mice treated with recombinant WISP1 protein, but not found in TLR4 knockout or TRIF knockout mice subjected to liver I/R. Taken together, WISP1 might contribute to hepatic ischemia reperfusion injury in mice and possibly depends on TLR4/TRIF signaling. PMID- 26821753 TI - Structure of a variable lymphocyte receptor-like protein from the amphioxus Branchiostoma floridae. AB - Discovery of variable lymphocyte receptors (VLRs) in agnathans (jawless fish) has brought the origin of adaptive immunity system (AIS) forward to 500 million years ago accompanying with the emergence of vertebrates. Previous findings indicated that amphioxus, a representative model organism of chordate, also possesses some homologs of the basic components of TCR/BCR-based AIS, but it remains unknown if there exist any components of VLR-based AIS in amphioxus. Bioinformatics analyses revealed the amphioxus Branchiostoma floridae encodes a group of putative VLR like proteins. Here we reported the 1.79 A crystal structure of Bf66946, which forms a crescent-shaped structure of five leucine-rich repeats (LRRs). Structural comparisons indicated that Bf66946 resembles the lamprey VLRC. Further electrostatic potential analyses showed a negatively-charged patch at the concave of LRR solenoid structure that might be responsible for antigen recognition. Site directed mutagenesis combined with bacterial binding assays revealed that Bf66946 binds to the surface of Gram-positive bacteria Staphylococcus aureus and Streptococcus pneumonia via a couple of acidic residues at the concave. In addition, the closest homolog of Bf66946 is highly expressed in the potential immune organ gill of Branchiostoma belcheri. Altogether, our findings provide the first structural evidence for the emergence of VLR-like molecules in the basal chordates. PMID- 26821754 TI - Climate change not to blame for late Quaternary megafauna extinctions in Australia. AB - Late Quaternary megafauna extinctions impoverished mammalian diversity worldwide. The causes of these extinctions in Australia are most controversial but essential to resolve, because this continent-wide event presaged similar losses that occurred thousands of years later on other continents. Here we apply a rigorous metadata analysis and new ensemble-hindcasting approach to 659 Australian megafauna fossil ages. When coupled with analysis of several high-resolution climate records, we show that megafaunal extinctions were broadly synchronous among genera and independent of climate aridity and variability in Australia over the last 120,000 years. Our results reject climate change as the primary driver of megafauna extinctions in the world's most controversial context, and instead estimate that the megafauna disappeared Australia-wide ~13,500 years after human arrival, with shorter periods of coexistence in some regions. This is the first comprehensive approach to incorporate uncertainty in fossil ages, extinction timing and climatology, to quantify mechanisms of prehistorical extinctions. PMID- 26821756 TI - Australian doctor challenges government over child detention "torture". PMID- 26821755 TI - White-nose syndrome without borders: Pseudogymnoascus destructans infection tolerated in Europe and Palearctic Asia but not in North America. AB - A striking feature of white-nose syndrome, a fungal infection of hibernating bats, is the difference in infection outcome between North America and Europe. Here we show high WNS prevalence both in Europe and on the West Siberian Plain in Asia. Palearctic bat communities tolerate similar fungal loads of Pseudogymnoascus destructans infection as their Nearctic counterparts and histopathology indicates equal focal skin tissue invasiveness pathognomonic for WNS lesions. Fungal load positively correlates with disease intensity and it reaches highest values at intermediate latitudes. Prevalence and fungal load dynamics in Palearctic bats remained persistent and high between 2012 and 2014. Dominant haplotypes of five genes are widespread in North America, Europe and Asia, expanding the source region of white-nose syndrome to non-European hibernacula. Our data provides evidence for both endemicity and tolerance to this persistent virulent fungus in the Palearctic, suggesting that host-pathogen interaction equilibrium has been established. PMID- 26821758 TI - Social behavior in deer mice as a novel interactive paradigm of relevance for obsessive-compulsive disorder (OCD). AB - Greater obsessive-compulsive (OC) symptom severity may be associated with poor social adjustment. Rather than possessing deficits in social skill per se, OCD patients may be more socially isolative in the presence of normal controls. We aimed to apply a novel social interaction challenge (SIC) to an established animal model of OCD, viz., the deer mouse, to assess complex social behavior in animals by investigating group sociability and its response to chronic escitalopram treatment (50 mg/kg/day * 28 days), both within and between non (N)- (viz., normal) and high (H)- (viz., OCD-like) stereotypical cohorts. Using automated screening, we scored approach behavior, episodes of proximity, duration of proximity, and relative net weighted movement. H animals socialized more with one another within cohort in all of the above parameters compared to the within cohort behavior of N animals. Furthermore, the social behavior of H animals toward one another, both within and between cohort demonstrated significant improvements following chronic escitalopram treatment. However, the study also demonstrates that the social interaction between H and N animals remain poor even after chronic escitalopram treatment. To conclude, findings from the current investigation support clinical data demonstrating altered sociability in patients with OCD. PMID- 26821757 TI - Probable involvement of p11 with interferon alpha induced depression. AB - Depression is one of the major side effects of interferon alpha (IFN-alpha) treatment, but the molecular mechanism underlying IFN-alpha-induced depression remains unclear. Several studies have shown that the serotonin receptors 5-HTR1b and 5-HTR4 play key roles in the anti-depression effects associated with p11 (S100A10). We investigated the effects of IFN-alpha on the regulation of p11, 5 HTR1b and 5-HTR4 in mice and human neuroblastoma cells (SH-sy5y). We found that intraperitoneal injection with IFN-alpha in Balb/c mice resulted in an increased immobility in FST and TST, and potently lowered the protein levels of p11, 5 HTR1b and 5-HTR4 in the hippocampus or cingulate gyrus. IFN-alpha significantly down-regulated the protein levels of p11, 5-HTR1b and 5-HTR4 in SH-sy5y cells, in a time- and dose-dependent manner. Our study revealed that over-expression of p11 could prevent the IFN-alpha-induced down-regulation of 5-HTR1b and 5-HTR4. The results indicated that IFN-alpha treatment resulted in p11 down-regulation, which subsequently decreased 5-HTR1b and 5-HTR4 in vitro or in vivo. Our findings suggested that p11 might be a potential regulator on 5-HTR1b and 5-HTR4 as well as a predictor of or a therapeutic target for IFN-alpha-induced depression. PMID- 26821759 TI - Leading causes of certifiable visual loss in England and Wales during the year ending 31 March 2013. AB - PURPOSE: The last article on causes of sight impairment (SI) in England and Wales was for April 2007-March 2008. This report updates these figures for April 2012 March 2013. METHODS: In England and Wales, registration for SI is initiated by completion of a certificate of vision impairment (CVI). The main cause of visual impairment was ascertained for certificates completed April 2012-March 2013. A proportional comparison against April 2007-March 2008 was made. RESULTS: We received 24 009 CVIs of which 10 410 were for severe sight impairment (SSI) and 13 129 were for SI. These numbers were slightly higher than those observed in April 2007-March 2008 (9823 SSI; 12 607 SI). The ratio SI:SSI has remained static with 55% of all certifications being SI. The proportion of certificates without a single main cause has fallen slightly (16.6 to 14%). The proportion of certificates with a main cause of degeneration of the macula and posterior pole (mostly age-related macular degeneration (AMD)) decreased from 58.6 to 50% SSI and from 57.2 to 52.5% SI. Glaucoma remains the second most common cause (11% SSI; 7.6% SI) but hereditary retinal disorders overtook diabetes as third leading cause of SSI. CONCLUSION: AMD is still by far the leading cause of certifications for sight impairment in England and Wales (both SI and SSI). Proportionate changes have been observed since 2008, but it is important to note that a proportionate increase in one condition will impact on others. PMID- 26821760 TI - Cannula-associated ocular injuries during cataract surgery: the North East England Study. PMID- 26821762 TI - Application of simplex-based experimental optimization to challenging bioprocess development problems: Case studies in downstream processing. AB - The identification of feasible operating conditions during the early stages of bioprocess development is implemented frequently through High Throughput (HT) studies. These typically employ techniques based on regression analysis, such as Design of Experiments. In this work, an alternative approach, based on a previously developed variant of the Simplex algorithm, is compared to the conventional regression-based method for three experimental systems involving polishing chromatography and protein refolding. This Simplex algorithm variant was found to be more effective in identifying superior operating conditions, and in fact it reached the global optimum in most cases involving multiple optima. By contrast, the regression-based method often failed to reach the global optimum, and in many cases reached poor operating conditions. The Simplex-based method is further shown to be robust in dealing with noisy experimental data, and requires fewer experiments than regression-based methods to reach favorable operating conditions. The Simplex-variant also lends itself to the use of HT analytical methods, when they are available, which can assist in avoiding analytical bottlenecks. It is suggested that this Simplex-variant is ideally suited to rapid optimization in early-phase process development. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:404-419, 2016. PMID- 26821763 TI - Recent Advances in Layered Metal Chalcogenides as Superconductors and Thermoelectric Materials: Fe-Based and Bi-Based Chalcogenides. AB - Recent advances in layered (Fe-based and Bi-based) chalcogenides as superconductors or functional materials are reviewed. The Fe-chalcogenide (FeCh) family are the simplest Fe-based high-Tc superconductors. The superconductivity in the FeCh family is sensitive to external or chemical pressure, and high Tc is attained when the local structure (anion height) is optimized. The Bi chalcogenide (BiCh2) family are a new group of layered superconductors with a wide variety of stacking structures. Their physical properties are also sensitive to external or chemical pressure. Recently, we revealed that the emergence of superconductivity and the Tc in this family correlate with the in-plane chemical pressure. Since the flexibility of crystal structure and electronic states are an advantage of the BiCh2 family for designing functionalities, I briefly review recent developments in this family as not only superconductors but also other functional materials. PMID- 26821761 TI - Management of inflammatory corneal melt leading to central perforation in children: a retrospective study and review of literature. AB - PURPOSE: To assess the outcome of early therapeutic penetrating keratoplasty (PKP) for corneal melt leading to perforation in children. METHODS: Case notes of all the consecutive patients presenting with acute corneal perforation that underwent urgent therapeutic PKP between 2000 and 2010 to the practice of one of the authors, both NHS at Great Ormond Street Hospital for Children and private, were retrospectively reviewed. Onset of perforation, underlying cause, medical and surgical treatment, pre- and post-operative visual acuity, graft clarity, length of follow-up, and post-operative complications were recorded. RESULTS: Four eyes of four consecutive patients (mean age of 9.5 years and median 8.5 years, range 4-17 years) were treated for acquired acute onset corneal perforations. There were three females and one male. Etiologies included herpes simplex keratitis secondary to immune recovery disease post bone marrow transplantation, acanthamoeba keratitis, recessive dystrophic epidermolysis bullosa, and blepharokeratoconjunctivitis with acne rosacea. Pre-operative visual acuity ranged from hand movements to 6/150. All the patients had severe anterior chamber inflammation. All eyes improved in visual acuity ranging from 6/9 to 6/18 with clear grafts at last follow-up. There was no recurrence of melt or perforation. Mean follow-up was 67 months (median 44 months). CONCLUSION: PKP during the acute phase together with aggressive medical therapy and close follow up may achieve good visual outcomes in children with corneal melt with perforation and should be considered. Waiting may sometimes allow the marked inflammatory response seen in children to cause irreversible structural and/or functional damage. PMID- 26821764 TI - What Drives National Differences in Intensive Grandparental Childcare in Europe? PMID- 26821765 TI - New Developments in Smart Bandage Technologies for Wound Diagnostics. AB - The pH of wound fluid has long been recognized as an important diagnostic for assessing wound condition, but as yet there are few technological options available to the clinician. The availability of sensors that can measure wound pH, either in the clinic or at home could significantly improve clinical outcome particularly in the early identification of complications such as infection. New material designs and electrochemical research strategies that are being targeted at wound diagnostics are identified and a critical overview of emerging research that could be pivotal in setting the direction for future devices is provided. PMID- 26821766 TI - A review on therapeutic contact lenses for ocular drug delivery. AB - Contact lenses for ophthalmic drug delivery have become very popular, due to their unique advantages like extended wear and more than 50% bioavailability. To achieve controlled and sustained drug delivery from contact lenses, researchers are working on various systems like polymeric nanoparticles, microemulsion, micelle, liposomes, use of vitamin E, etc. Numerous scientists are working on different areas of therapeutic contact lenses to treat ocular diseases by implementing techniques like soaking method, molecular imprinting, entrapment of drug-laden colloidal nanoparticles, drug plate/film, ion ligand polymeric systems, supercritical fluid technology, etc. Though sustained drug delivery was achieved using contact lens, the critical properties such as water content, tensile strength (mechanical properties), ion permeability, transparency and oxygen permeability were altered, which limit the commercialization of therapeutic contact lenses. Also issues like drug stability during processing/fabrication (drug integrity test), zero order release kinetics (prevent burst release), drug release during monomer extraction step after fabrication (to remove un-reacted monomers), protein adherence, drug release during storage in packaging solution, shelf life study, cost-benefit analysis, etc. are still to be addressed. This review provides an expert opinion on different methodology to develop therapeutic contact lenses with special remark of their advantages and limitations. PMID- 26821768 TI - Augmenting outcomes in advanced heart failure: a lot to learn. PMID- 26821767 TI - Two methods to adapt the human haemoglobin-oxygen dissociation algorithm to the blood of white rhinoceros (Ceratotherium simum) and to determine the accuracy of pulse oximetry. AB - OBJECTIVES: To adapt the algorithm for the calculation of oxygen saturation to the blood characteristics of the white rhinoceros by two different methods and to determine the accuracy of conventional pulse oximetry measurements. STUDY DESIGN: Adaptation of two mathematical models of the oxygen dissociation curve (ODC). ANIMALS: Twenty-five captive white rhinoceros (Ceratotherium simum), including 12 males and 13 females, aged 6-32 years. METHODS: During 33 anaesthetic events, 94 arterial blood gas samples with 72 simultaneous pulse oximetry measurements were analysed. The calculation of oxygen saturation was adapted to the characteristics of rhinoceros blood using two different methods. Firstly, a mathematical model developed in 1984 and, secondly, an oxygen status algorithm (OSA) produced by the same developer in 2005 were tested for their applicability for clinical use. RESULTS: When arterial partial pressure of oxygen is >7.98 kPa (60 mmHg), oxygen saturation exceeds 95%. At partial pressures of 6.12-6.52 kPa (46-49 mmHg) Method 1 determined oxygen saturations of 92.5-95.3% and Method 2 oxygen saturations of 90.2-91.6%. Both methods resulted in similar ODCs and accounted for the low p50 value of rhinoceros blood. Method 1 provided better adaptation in respect to the physiological parameters of the rhinoceros, especially with regard to the Bohr effect, than Method 2. Pulse oximetry was an unreliable method of monitoring arterial oxygen saturation during general anaesthesia in this species. CONCLUSION: Adapting the oxygen saturation algorithm to consider the left shift of the ODC provides a useful tool for monitoring oxygen status, especially as pulse oximetry is insufficiently accurate. Experimental determination of the complete Hill curve is required to further validate and optimize the algorithm for use in the white rhinoceros. CLINICAL RELEVANCE: The method will facilitate the accurate interpretation of oxygen saturation calculated by blood gas analysis in white rhinoceros. PMID- 26821769 TI - The effects of low-dose ketamine on the prefrontal cortex and amygdala in treatment-resistant depression: A randomized controlled study. AB - BACKGROUND: Low-dose ketamine has been found to have robust and rapid antidepressant effects. A hypoactive prefrontal cortex (PFC) and a hyperactive amygdala have been suggested to be associated with treatment-resistant depression (TRD). However, it is unclear whether the rapid antidepressant mechanisms of ketamine on TRD involve changes in glutamatergic neurotransmission in the PFC and the amygdala. METHODS: A group of 48 TRD patients were recruited and equally randomized into three groups (A: 0.5 kg/mg-ketamine; B: 0.2 kg/mg-ketamine; and C: normal saline [NS]). Standardized uptake values (SUV) of glucose metabolism measured by (18) F-FDG positron-emission-tomography before and immediately after a 40-min ketamine or NS infusion were used for subsequent region-of-interest (ROI) analyses (a priori regions: PFC and amygdala) and whole-brain voxel-wise analyses and were correlated with antidepressant responses, as defined by the Hamilton depression rating scale score. The (18) F-FDG signals were used as a proxy measure of glutamate neurotransmission. RESULTS: The ROI analysis indicated that Group A and Group B, but not Group C, had increases in the SUV of the PFC (group-by-time interaction: F = 7.373, P = 0.002), whereas decreases in the SUV of the amygdala were observed in all three groups (main effect of time, P < 0.001). The voxel-wise analysis further confirmed a significant group effect on the PFC (corrected for family-wise errors, P < 0.05; post hoc analysis: Group A50% adherence, the effect was 0.38 (95% CI 0.17, 0.58, p < 0.0005). Within the active arm, each 10% greater adherence was associated with a 0.06 (95% CI 0.01, 1.17, p = 0.03) greater increase in spine QCT BMD Z-score. Treatment response did not vary according to baseline body mass index (BMI) Z-score, pubertal status, CD severity, or concurrent glucocorticoid or biologic medications. In all participants combined, height, pQCT trabecular BMD, and cortical area and DXA outcomes improved significantly. In conclusion, LMMS was associated with increases in vertebral trabecular BMD by QCT; however, no effects were observed at DXA or pQCT sites. (c) 2016 American Society for Bone and Mineral Research. PMID- 26821781 TI - Reduced duration of untreated illness over time in patients with schizophrenia spectrum, mood and anxiety disorders. AB - AIMS: Psychiatric disorders represent highly impairing conditions, often underdiagnosed and undertreated, with a conspicuous duration of untreated illness (DUI). Given that social and cultural factors influence the DUI and assuming that progress in diagnosis and treatment determines a reduced latency to pharmacotherapy, we assessed and compared DUI and related variables in a large sample of psychiatric patients (n = 562) whose onset occurred within three different a priori-defined epochs. METHODS: Two temporal cut-offs were established - the year 1978, when Law 180 (redefining standards for mental care) was introduced in Italy, and the year 2000 - in order to divide patients into three subgroups: onset before 1978, onset 1978-2000 and onset after 2000. RESULTS: A significant difference in terms of age at onset, age at first diagnosis and age at first treatment was observed in patients with onset 1978 2000 and in those with onset after 2000. In addition, a significant reduction of the DUI was found across epochs (onset before 1978: 192.25 +/- 184.52 months; onset 1978-2000: 77.00 +/- 96.63 months; and onset after 2000: 19.00 +/- 31.67 months; P < 0.001). Furthermore, the proportion of patients with onset-related stressful events, use of benzodiazepines and neurological referral was found to be significantly different between the three epochs (chi(2) = 23.4, P < 0.001; chi(2) = 9.92, P = 0.007; chi(2) = 16.50, P = 0.011). CONCLUSIONS: Present data indicate a progressive, statistically significant reduction of latency to treatment and other related changes across subsequent epochs of onset in patients with different psychiatric disorders. Future studies will assess specific changes within homogeneous diagnostic subgroups. PMID- 26821782 TI - Isolation, identification, and characterization of gut microflora of Perionyx excavatus collected from Midnapore, West Bengal. AB - Agriculture is an important part of the economy of the undivided Midnapore district. Agricultural land is its asset and most importantly its means of sustenance as well as survival. Earthworms are invertebrates that play a key role in recycling organic matters in soils. Since the intestines of earthworms harbor wide ranges of microorganisms, enzymes, hormones etc., these half digested materials decompose rapidly and are transformed into a stabilized material called vermicompost which is very useful for increasing the soil fertility. One has to look for these characters before recommending any species for vermiculture. In the present study, Perionyx excavatus specimens were collected from the undivided Midnapore district and from the Earthworms gut, bacteria, fungus, actinobacteria, and yeast were isolated and identified using various morphological and biochemical tests. All the bacterial isolates were identified using morphological study, staining techniques, and different biochemical tests such as catalase test, KOH test, H2 SO4 test, Starch hydrolysis test, oxidase test, and sucrose hydrolysis test. All the fungal, actinobacteria, and yeast isolates were subjected to staining and morphological characterization (color and texture of fungal colony). Bacterial isolates of genus Bacillus sp., Staphylococcus sp., Enterococci, Micrococcus sp., Enterobacter sp., and Citrobacter sp. were identified. Among the fungal isolates Aspergilus sp., and P. boydii were identified. Streptomyces sp., Nocardia sp. among the actinobacteria and Candida sp. among yeast were also found to be present in earthworm gut and these might play an important role along with the earthworm to increase the quality and fertility of soil. PMID- 26821783 TI - A three-groups model for high-throughput survival screens. AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive deterioration of motor neurons in the cortex and spinal cord. Using an automated robotic microscope platform that enables the longitudinal tracking of thousands of single neurons, we examine the effects a large library of compounds on modulating the survival of primary neurons expressing a mutation known to cause ALS. The goal of our analysis is to identify the few potentially beneficial compounds among the many assayed, the vast majority of which do not extend neuronal survival. This resembles the large-scale simultaneous inference scenario familiar from microarray analysis, but transferred to the survival analysis setting due to the novel experimental setup. We apply a three-component mixture model to censored survival times of thousands of individual neurons subjected to hundreds of different compounds. The shrinkage induced by our model significantly improves performance in simulations relative to performing treatment-wise survival analysis and subsequent multiple testing adjustment. Our analysis identified compounds that provide insight into potential novel therapeutic strategies for ALS. PMID- 26821784 TI - Novel perspectives on the hepatitis B virus vaccine in the chronic kidney disease population. AB - BACKGROUND: The prevalence and incidence rates of hepatitis B virus (HBV) among patients undergoing maintenance dialysis in developed countries have declined over the last 2 decades thanks to the implementation of numerous infection control procedures in dialysis units, including the hepatitis B vaccine. It is well known that the immune response against HBV vaccine is unsatisfactory in the chronic kidney disease (CKD) population. The seroprotection rate after the HB vaccine schedule is low and the anti-HB titers are reduced, falling logarithmically over time. PURPOSE: We did an extensive review of the medical literature on the mechanisms underlying the reduced response rate towards the HBV vaccine in patients with CKD. The efficacy and safety of HBV vaccines for use in the CKD population was also evaluated. RESULTS: Currently available vaccines against HBV are mostly plasma-derived or manufactured by recombinant DNA technology (yielding the S protein of the HBV envelope). The most promising strategy to enhance the immune response toward the HBV vaccine in the dialysis population is given by adjuvanted vaccines. Second-generation recombinant HB vaccines provided with a novel adjuvant (AS04, made of 3-O-4'-desacyl monophosphoryl lipid A adsorbed on aluminum phosphate) demonstrated improved immunogenicity but a number of patients with an unsatisfactory response still occurs. Additional second-generation vaccines containing nonaluminum-based adjuvant systems such as AS02 (3-O-desacyl-4'-monophoshoryl lipid A and QS21) or 1018 (a Toll-like receptor 9 agonist) have shown higher immunogenicity and acceptable safety in the CKD population. The evidence in patients with end-stage renal disease is extremely limited on the use of third-generation vaccines, recombinant HBV vaccines expressed in mammalian cells containing S/Pre-S antigens. CONCLUSIONS: The immunogenicity of HBV vaccines in patients with CKD is suboptimal but novel technologies promise to give better results in the near future. PMID- 26821785 TI - A New Equation Solver for Modeling Turbulent Flow in Coupled Matrix-Conduit Flow Models. AB - Karst aquifers represent dual flow systems consisting of a highly conductive conduit system embedded in a less permeable rock matrix. Hybrid models iteratively coupling both flow systems generally consume much time, especially because of the nonlinearity of turbulent conduit flow. To reduce calculation times compared to those of existing approaches, a new iterative equation solver for the conduit system is developed based on an approximated Newton-Raphson expression and a Gaubeta-Seidel or successive over-relaxation scheme with a single iteration step at the innermost level. It is implemented and tested in the research code CAVE but should be easily adaptable to similar models such as the Conduit Flow Process for MODFLOW-2005. It substantially reduces the computational effort as demonstrated by steady-state benchmark scenarios as well as by transient karst genesis simulations. Water balance errors are found to be acceptable in most of the test cases. However, the performance and accuracy may deteriorate under unfavorable conditions such as sudden, strong changes of the flow field at some stages of the karst genesis simulations. PMID- 26821786 TI - Control of local structures and photophysical properties of zinc porphyrin-based supramolecular assemblies structurally organized by regioselective ligand coordination. AB - Nano- and micro-sized molecular assemblies of zinc porphyrins [5,10,15,20 tetrakis(4-carboxyphenyl)porphyrinato-zinc(II) (ZnTCPP)] utilizing bridging nitrogen ligands such as diazabicycro[2.2.2]octane (DABCO) were prepared to demonstrate the regioselective coordination by two different synthetic strategies such as (I) the solvothermal method and (II) the colloidal metal organic framework (MOF) method. The initial organization process is a planar checkerboard patterned formation (2D platform) of zinc porphyrins organized by paddlewheel secondary building units (PSBUs) between carboxylate and zinc ions. Then, DABCO moieties are decorated on zinc atoms in the metal centres of the porphyrin rings (m-cPDC) in the solvothermal method, whereas the metal centres in the porphyrin rings (n-uPDC) remain uncoordinated in the colloidal MOF method. These internal structural changes between m-cPDC and n-uPDC are in sharp contrast with the corresponding reference systems using ZnTCPP and a 4,4'-bipyridine (BPY) ligand (i.e., m-cPBC and n-cPBC). Concretely, the metal centres of zinc porphyrins in n uPDC were unsaturated and uncoordinated with the DABCO ligands, which was confirmed by XRD and steady-state spectroscopic measurements. These different coordination features have great effect on the spectroscopic and photophysical properties. For example, the average fluorescence lifetime of m-cPDC is much smaller than that of n-uPDC because of the acceleration of nonradiative processes, which are highly related with the coordination of DABCO to the Zn(II) centre of the ZnTCPP unit. Finally, fluorescence quenching experiments via photoinduced electron transfer (PET) utilizing an electron acceptor: benzoquinone (BQ) were performed. The apparent association constant (Kapp) of n-uPDC is larger than that of m-cPDC. This suggested that the unsaturated ZnTCPP units embedded in n-uPDC easily accommodate guest molecules as compared to the other systems. PMID- 26821787 TI - Enhancement of N-heterocyclic carbenes on rhodium catalyzed olefination of triazoles. AB - A few rhodium complexes of N-heterocyclic carbenes were prepared through carbene transfer reactions and their structures were characterized by X-ray diffraction analysis. The rhodium complexes of NHCs are found to be efficient catalysts for vinylation of various triazoles via C-H activation. A number of double vinylated triazoles can be obtained in good yields. PMID- 26821788 TI - Layer-by-layer thinning of two-dimensional MoS2 films by using a focused ion beam. AB - A layer-controlled two-dimensional (2D) molybdenum disulfide (MoS2) film with tunable bandgaps is highly desired for the fabrication of electronic/photoelectronic devices. In this work, we demonstrate that a focused ion beam (FIB) can be applied to thin MoS2 films layer-by-layer. The layer number can be controlled by simply changing the Ga(+) beam exposure time and the thinning speed is about half a layer per second. OM, AFM, PL and Raman spectra were used to monitor the change of layer numbers and characterize the morphology, thickness, and homogeneity of MoS2 films. The FIB layer-by-layer thinning technology will establish a new methodology for rationally thinning all kinds of 2D layered materials. PMID- 26821790 TI - Barriers and facilitators of evidence-based management of patients with bacterial infections among general dental practitioners: a theory-informed interview study. AB - BACKGROUND: General dental practitioners (GDPs) regularly prescribe antibiotics to manage dental infections although most infections can be treated successfully by local measures. Published guidance to support GDPs to make appropriate prescribing decisions exists but there continues to be wide variation in dental antibiotic prescribing. An interview study was conducted as part of the Reducing Antibiotic Prescribing in Dentistry (RAPiD) trial to understand the barriers and facilitators of using local measures instead of prescribing antibiotics to manage bacterial infections. METHODS: Thirty semi-structured one-to-one telephone interviews were conducted using the Theoretical Domains Framework (TDF). Responses were coded into domains of the TDF and sub-themes. Priority domains (high frequency: >=50 % interviewees discussed) relevant to behaviour change were identified as targets for future intervention efforts and mapped onto 'intervention functions' of the Behaviour Change Wheel system. RESULTS: Five domains (behavioural regulation, social influences, reinforcement, environmental context and resources, and beliefs about consequences) with seven sub-themes were identified as targets for future intervention. All participants had knowledge about the evidence-based management of bacterial infections, but they reported difficulties in following this due to patient factors and time management. Lack of time was found to significantly influence their decision processes with regard to performing local measures. Beliefs about their capabilities to overcome patient influence, beliefs that performing local measures would impact on subsequent appointment times as well as there being no incentives for performing local measures were also featured. Though no knowledge or basic skills issues were identified, the participants suggested some continuous professional development programmes (e.g. time management, an overview of published guidance) to address some of the barriers. The domain results suggest a number of intervention functions through which future interventions could change GDPs' antibiotic prescribing for bacterial infections: imparting skills through training, providing an example for GDPs to imitate (i.e. modelling) or creating the expectation of a reward (i.e. incentivisation). CONCLUSIONS: This is the first theoretically informed study to identify barriers and facilitators of evidence-based management of patients with bacterial infections among GDPs. A pragmatic approach is needed to address the modifiable barriers in future interventions intended to change dentists' inappropriate prescribing behaviour. PMID- 26821792 TI - Modeling and simulation of protein-surface interactions: achievements and challenges. AB - Understanding protein-inorganic surface interactions is central to the rational design of new tools in biomaterial sciences, nanobiotechnology and nanomedicine. Although a significant amount of experimental research on protein adsorption onto solid substrates has been reported, many aspects of the recognition and interaction mechanisms of biomolecules and inorganic surfaces are still unclear. Theoretical modeling and simulations provide complementary approaches for experimental studies, and they have been applied for exploring protein-surface binding mechanisms, the determinants of binding specificity towards different surfaces, as well as the thermodynamics and kinetics of adsorption. Although the general computational approaches employed to study the dynamics of proteins and materials are similar, the models and force-fields (FFs) used for describing the physical properties and interactions of material surfaces and biological molecules differ. In particular, FF and water models designed for use in biomolecular simulations are often not directly transferable to surface simulations and vice versa. The adsorption events span a wide range of time- and length-scales that vary from nanoseconds to days, and from nanometers to micrometers, respectively, rendering the use of multi-scale approaches unavoidable. Further, changes in the atomic structure of material surfaces that can lead to surface reconstruction, and in the structure of proteins that can result in complete denaturation of the adsorbed molecules, can create many intermediate structural and energetic states that complicate sampling. In this review, we address the challenges posed to theoretical and computational methods in achieving accurate descriptions of the physical, chemical and mechanical properties of protein-surface systems. In this context, we discuss the applicability of different modeling and simulation techniques ranging from quantum mechanics through all-atom molecular mechanics to coarse-grained approaches. We examine uses of different sampling methods, as well as free energy calculations. Furthermore, we review computational studies of protein-surface interactions and discuss the successes and limitations of current approaches. PMID- 26821793 TI - NaHCO3-enhanced hydrogen production from water with Fe and in situ highly efficient and autocatalytic NaHCO3 reduction into formic acid. AB - We report a highly efficient water splitting for CO2 reduction into formic acid with a commercially available metal of Fe powder without adding any other catalyst. An excellent formic acid yield of more than 90% was attained. PMID- 26821791 TI - Factors Associated With Ocular Health Care Utilization Among Hispanics/Latinos: Results From an Ancillary Study to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). AB - IMPORTANCE: Regular ocular care is critical to early detection and prevention of eye disease and associated morbidity and mortality; however, there have been relatively few studies of ocular health care utilization among Hispanics/Latinos of diverse backgrounds. OBJECTIVE: To examine factors associated with ocular health care utilization among Cuban, Central American, and South American Hispanics/Latinos in a cohort study. DESIGN, SETTING, AND PARTICIPANTS: An ancillary study to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) evaluating ocular health, knowledge, risk factors, and health care use was conducted with 1235 HCHS/SOL participants (aged >=40 years) at the Miami, Florida, study site. Data were collected from October 17, 2011, to September 30, 2013, and analyses were conducted from May 28, 2014, to March 18, 2015. Descriptive and multivariable logistic regression analyses were performed for 3 ocular health care outcomes. Regression models were built sequentially with variables conceptually grouped according to Andersen's Behavioral Model of Health Services Use. MAIN OUTCOMES AND MEASURES: Ever having an eye examination, having an eye examination performed within the past 2 years, and difficulty obtaining needed eye care in the past year. RESULTS: Of the 1235 participants, 478 were men and 757 were women, and they had a mean (SD) age of 53.6 (8.1) years. Those who never had insurance were less likely to have had an eye examination (with data reported as odds ratios [95% CIs]) ever, 0.19 (0.07-0.53) and in the past 2 years, 0.22 (0.15-0.33) and were more likely to have had difficulty obtaining needed eye care in the past year (3.72 [1.75-7.93]). Those with less than excellent or good self-rated eyesight were less likely to ever have had an eye examination (0.26 [0.12-0.56]) and more likely to have had difficulty obtaining care (3.00 [1.48-6.11]). Men were less likely to ever have had an eye examination (0.31 [0.18-0.53]). Older (55-64 years) Hispanics/Latinos (3.04 [1.47-6.31]) and those with a high school degree or general educational development certification (2.06 [1.02-4.13]) or higher levels of education (4.20 [2.12-8.30]) were more likely to ever have had an eye examination. Finally, those living in the United States for more than 15 years (0.42 [0.21-0.82]) were less likely to have had difficulty obtaining care. CONCLUSIONS AND RELEVANCE: Our findings suggest that increasing insurance coverage, decreasing the costs of care, and increasing the availability of care for Hispanics/Latinos with poor self-rated eyesight are relevant issues to address to improve ocular health care use among Hispanics/Latinos of diverse backgrounds. PMID- 26821794 TI - Evaluating the Influence of Nutrition Determinants on Construction Workers' Food Choices. AB - Nutritional knowledge as well as economic, social, biological, and cultural factors have been known to determine an individual's food choices. Despite the existence of research on the factors which influence nutrition globally, there is little known about the extent to which these factors influence the food choices of construction workers, which in turn influence their health and safety during construction activities. The present article investigates the extent to which construction workers' nutrition is influenced by nutritional knowledge, as well as economic, environmental, social, psychological, and physiological factors. A field questionnaire survey was conducted on site construction workers in the Gauteng Province of South Africa. Principal components analysis and multiple regression analysis were used to analyze the data. Findings revealed that consumption of foods termed alternative foods including dairy products, eggs, nuts, fish, and cereals, was influenced by nutritional knowledge and resources. Foods termed traditional core foods were influenced by cultural background; foods termed secondary core foods comprising fruits and vegetables were influenced by economic factors, resources, and cultural background; while foods termed core foods were mostly influenced by nutritional knowledge. By providing evidence of the factors which most influence selection and consumption of certain foods by construction workers, relevant nutrition interventions will be designed and implemented, taking cognizance of these factors. PMID- 26821795 TI - Increased plasma dipeptidyl peptidase-4 activities are associated with high prevalence of diabetic nephropathy in Chinese patients with newly diagnosed type 2 diabetes: A cross-sectional study. AB - OBJECTIVE: To investigate the association between plasma Dipeptidyl peptidase-4 (DPP4) activities and diabetic nephropathy in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 1193 newly diagnosed type 2 diabetic subjects were studied. Plasma DPP4 activity, mannose 6-phosphate receptor, inflammatory markers and oxidative stress parameters were measured in all participants. Diabetic nephropathy was defined as the presence of albuminuria or an estimated glomerular filtration rate < 60 mL/min/1.73 m(2). RESULTS: Participants in the highest quartile of DPP4 activity had higher HbA1c, homeostatic model assessment of insulin resistance, nitrotyrosine, 8-iso-PGF2a, interleukin-6, high-sensitivity C reactive protein, mannose 6-phosphate receptor, urinary albumin-to-creatinine ratio and lower estimated glomerular filtration rate compared with participants in the lowest quartile (all p < 0.001). DPP4 activities were associated positively with HbA1c, homeostatic model assessment of insulin resistance, nitrotyrosine, 8-iso-PGF2a, interleukin-6, high-sensitivity C-reactive protein, mannose 6-phosphate receptor, urinary albumin-to-creatinine ratio and negatively with estimated glomerular filtration rate (all p < 0.001). In the highest DPP4 quartile, diabetic nephropathy risk was significantly higher (odds ratio: 3.77; 95% confidence interval: 2.34-6.07) than in the lowest quartile after adjustment for potential confounders. This association remained strong (2.85; 1.74-4.68) after further controlling for HbA1c, homeostatic model assessment of insulin resistance, nitrotyrosine and high-sensitivity C-reactive protein. CONCLUSION: This study shows that increased DPP4 activities are strongly and independently associated with diabetic nephropathy in type 2 diabetes. The associations between DPP4 and diabetic nephropathy, although strong, do not imply causality. There are however plausible mechanisms which could explain such a link. PMID- 26821796 TI - Promoter polymorphism at the tumour necrosis factor/lymphotoxin-alpha locus is associated with type of diabetes but not with susceptibility to sight-threatening diabetic retinopathy. AB - AIM: To investigate, in a large cohort of 2494 individuals with diabetes mellitus, whether functional single nucleotide polymorphisms in the promoter region of tumour necrosis factor (TNF) and lymphotoxin-alpha (LTA) genes are associated with type of diabetes or presence of diabetic retinopathy. METHODS: A total of 334 type 1 diabetes and 999 type 2 diabetes participants with sight threatening diabetic retinopathy, and 260 type 1 diabetes and 901 type 2 diabetes participants with no diabetic retinopathy or minimal non-proliferative diabetic retinopathy, were genotyped for two single nucleotide polymorphisms (rs1800629 and rs361525). RESULTS: The A allele of rs1800629 was associated with type 1 diabetes (p < 0.001; odds ratio = 0.62). After adjustment for age, sex, diabetes duration, HbA1c, hypertension and nephropathy, no significant association was found between rs1800629 or rs361525 and sight-threatening diabetic retinopathy. CONCLUSION: An association between the A allele of rs1800629 and type of diabetes was found. No association was found between two promoter variants of TNF and LTA, and diabetic retinopathy in a large cohort of Caucasian patients with type 1 diabetes and type 2 diabetes. PMID- 26821797 TI - Video transparency: a powerful tool for patient safety and quality improvement. PMID- 26821798 TI - Patient-centred care: confessions of a pragmatist. PMID- 26821799 TI - What drives the consistent use of long-lasting insecticidal nets over time? A multi-method qualitative study in mid-western Uganda. AB - BACKGROUND: The distribution of long-lasting insecticidal nets (LLINs) through universal coverage campaigns is a widely adopted approach for the prevention of malaria at scale. While post-distribution surveys play a valuable role in determining cross-sectional levels of LLIN retention and use, as well as frequently cited reasons for non-use, few studies have explored the consistency of LLIN use over time, within the expected lifespan of the net, and the factors which may drive this. METHODS: In this qualitative study, 74 in-depth interviews were conducted with (male) household heads and (female) caregivers of children in LLIN recipient households, as well as community health workers, in Buliisa, Hoima and Kiboga districts in Uganda, 25-29 months following a LLIN mass campaign distribution. A triangulation approach to data analysis was taken, incorporating thematic analysis, most significant change and positive deviance. RESULTS: The factors found to be most influential in encouraging long-term LLIN use were positive experience of net use prior to the distribution, and appreciation or awareness of a range of benefits arising from their use, including protection from malaria as well as importantly, other health, lifestyle, social and economic benefits. Social support from within the community was also identified as an important factor in determining continued use of LLINs. Net use appeared to be more consistent amongst settled urban and rural communities, compared with fishing, pastoralist, refugee and immigrant communities. CONCLUSIONS: A multitude of interplaying factors encouraged consistent LLIN use in this setting. Whilst the protection of malaria remains a powerful motivator, social and behaviour change (SBC) strategies should also capitalize on the non-malaria benefits of net use that provide a long-term rationale for consistent use. Where supplies are available, SBC campaigns should promote replacement options, emphasizing ongoing net care and replacement as a household responsibility, thus reducing dependence on free distributions. The triangulation approach to qualitative data analysis enabled increased confidence in the validity of findings and an enhanced contextual understanding of the factors promoting consistent net use in mid western Uganda. The approach should be considered when designing future studies to explore factors driving net retention and use trends. PMID- 26821800 TI - A two-phase procedure for non-normal quantitative trait genetic association study. AB - BACKGROUND: The nonparametric trend test (NPT) is well suitable for identifying the genetic variants associated with quantitative traits when the trait values do not satisfy the normal distribution assumption. If the genetic model, defined according to the mode of inheritance, is known, the NPT derived under the given genetic model is optimal. However, in practice, the genetic model is often unknown beforehand. The NPT derived from an uncorrected model might result in loss of power. When the underlying genetic model is unknown, a robust test is preferred to maintain satisfactory power. RESULTS: We propose a two-phase procedure to handle the uncertainty of the genetic model for non-normal quantitative trait genetic association study. First, a model selection procedure is employed to help choose the genetic model. Then the optimal test derived under the selected model is constructed to test for possible association. To control the type I error rate, we derive the joint distribution of the test statistics developed in the two phases and obtain the proper size. CONCLUSIONS: The proposed method is more robust than existing methods through the simulation results and application to gene DNAH9 from the Genetic Analysis Workshop 16 for associated with Anti-cyclic citrullinated peptide antibody further demonstrate its performance. PMID- 26821801 TI - A Human Renal Proximal Tubule Cell Line with Stable Organic Anion Transporter 1 and 3 Expression Predictive for Antiviral-Induced Toxicity. AB - Drug-induced nephrotoxicity still hampers drug development, because current translation from in vitro or animal studies to human lacks high predictivity. Often, renal adverse effects are recognized only during clinical stages of drug development. The current study aimed to establish a robust and a more complete human cell model suitable for screening of drug-related interactions and nephrotoxicity. In addition to endogenously expressed renal organic cation transporters and efflux transporters, conditionally immortalized proximal tubule epithelial cells (ciPTEC) were completed by transduction of cells with the organic anion transporter (OAT) 1 or OAT3. Fluorescence-activated cell sorting upon exposure to the OAT substrate fluorescein successfully enriched transduced cells. A panel of organic anions was screened for drug-interactions in ciPTEC OAT1 and ciPTEC-OAT3. The cytotoxic response to the drug-interactions with antivirals was further examined by cell viability assays. Upon subcloning, concentration-dependent fluorescein uptake was found with a higher affinity for ciPTEC-OAT1 (Km = 0.8 +/- 0.1 MUM) than ciPTEC-OAT3 (Km = 3.7 +/- 0.5 MUM). Co exposure to known OAT1 and/or OAT3 substrates (viz. para-aminohippurate, estrone sulfate, probenecid, furosemide, diclofenac, and cimetidine) in cultures spanning 29 passage numbers revealed relevant inhibitory potencies, confirming the robustness of our model for drug-drug interactions studies. Functional OAT1 was directly responsible for cytotoxicity of adefovir, cidofovir, and tenofovir, while a drug interaction with zidovudine was not associated with decreased cell viability. Our data demonstrate that human-derived ciPTEC-OAT1 and ciPTEC-OAT3 are promising platforms for highly predictive drug screening during early phases of drug development. PMID- 26821802 TI - Pre-existing Antibody: Biotherapeutic Modality-Based Review. AB - Pre-existing antibodies to biotherapeutic drugs have been detected in drug-naive subjects for a variety of biotherapeutic modalities. Pre-existing antibodies are immunoglobulins that are either specific or cross-reacting with a protein or glycan epitopes on a biotherapeutic compound. Although the exact cause for pre existing antibodies is often unknown, environmental exposures to non-human proteins, glycans, and structurally similar products are frequently proposed as factors. Clinical consequences of the pre-existing antibodies vary from an adverse effect on patient safety to no impact at all and remain highly dependent on the biotherapeutic drug modality and therapeutic indication. As such, pre existing antibodies are viewed as an immunogenicity risk factor requiring a careful evaluation. Herein, the relationships between biotherapeutic modalities to the nature, prevalence, and clinical consequences of pre-existing antibodies are reviewed. Initial evidence for pre-existing antibody is often identified during anti-drug antibody (ADA) assay development. Other interfering factors known to cause false ADA positive signal, including circulating multimeric drug target, rheumatoid factors, and heterophilic antibodies, are discussed. PMID- 26821803 TI - Sample Management: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team. AB - The importance of appropriate sample management in regulated bioanalysis is undeniable for clinical and non-clinical study support due to the fact that if the samples are compromised at any stage prior to analysis, the study results may be affected. Health authority regulations do not contain specific guidance on sample management; therefore, as part of the Global Bioanalysis Consortium (GBC), the A5 team was established to discuss sample management requirements and to put forward recommendations. The recommendations from the team concern the entire life span of the sample and include the following: 1. Sampling procedures should be described in the protocol or within the laboratory manual. This information should include the volume of the sample to be collected, the required anticoagulant, light sensitivity, collection and storage containers, and labeling with a unique identifier. 2. The correct procedures for processing and then storing the samples after collection at the clinical/non-clinical testing site and during shipment are also very important to ensure the analyte(s) stability and should be documented. 3. Chain of custody for the samples must be maintained throughout the complete life span of each sample. This is typically maintained via paper and electronic data systems, including Laboratory Information Management Systems (LIMS) where available. 4. Pre- and post-analysis storage location and conditions must also be clearly defined at the analytical laboratory. The storage temperature of the samples must be traceable and controlled by monitoring and warning alerts. The team suggests moving away from using temperatures and to adopt standard terminology of "room temperature," "refrigerator," "freezer," and "ultra-freezer" that have defined and industry wide accepted temperature ranges. 5. At the end of the study, documentation of the samples' disposal is required. PMID- 26821804 TI - Gait dynamics in the wide spectrum of children with arthrogryposis: a descriptive study. AB - BACKGROUND: Arthrogryposis Multiplex Congenita (AMC) is a heterogeneous condition characterized by multiple joint contractures at birth. Greater movements in the trunk and pelvis during walking have been observed in children with AMC using orthoses compared to those wearing only shoes. This study investigated gait dynamics in children with AMC and identified compensatory mechanisms that accommodate walking. METHODS: Twenty-six children with AMC who walked with orthoses or shoes and a control group consisting of 37 typically-developing children were evaluated in 3D gait analysis. Children with AMC were divided into subgroups based on which joints needed to be stabilized in the sagittal plane; AMC1 used knee-ankle-foot orthoses (KAFOs) with locked knee joints, AMC2 used KAFOs with open knee joints or ankle-foot orthoses, and AMC3 used shoes. RESULTS: The Gait Deviation Index was lower in AMC groups than in the control group, with the lowest in AMC1. Excessive trunk movements in frontal and transverse planes were observed in AMC2 and especially in AMC1. Lower hip flexion moment was found in AMC1, while AMC2 and AMC3 showed similar hip flexion moments as the control group. Knee extension moments were similar between the groups. In the frontal plane there were only small differences between the groups in hip abduction moment. A joint work analysis indicated greater contribution from the hip muscles to overall positive work in AMC groups, particularly in AMC1, than in the control group. CONCLUSION: All AMC groups showed less hip extension than the control group, but hip flexion moment was significantly lower only in AMC1, which can be attributed to their gait strategy with bilateral locked KAFOs. AMC1, who had weak knee extensors, were helped by their locked KAFOs and therefore showed similar knee extension moment as the other groups. This finding, together with their gait patterns, demonstrates the children's high reliance on hip muscles and presumably trunk muscles to provide propulsion. Our study shows that with adequate orthotic support, children with AMC and even with severe weakness and contractures can achieve walking. PMID- 26821806 TI - Marinomonas spartinae sp. nov., a novel species with plant-beneficial properties. AB - Two strains of Gram-stain-negative, chemo-organotrophic, aerobic and halophilic gammaproteobacteria, isolated from within the stem and roots of Spartina maritima in salt marshes from the south Atlantic Spanish coast, were found to represent a novel species in the genus Marinomonas through phylogenetic analysis of their 16S rRNA genes and phenotypic characterization. 16S rRNA gene sequences of the two strains shared < 96.2% similarity with other Marinomonas species, with Marimonas alcarazii being the most similar in sequence. They required sodium ions for growth, were able to thrive at low (4 degrees C) temperatures and at salinities of 12-15%, were unable to hydrolyse any tested macromolecule except casein, and grew with different monosaccharides, disaccharides, sugar alcohols, organic acids and amino acids. The novel species differed from other Marinomonas species in the use of several sole carbon sources, its temperature and salinity ranges for growth, ion requirements and cellular fatty acid composition, which included C16:0, C16:1 and C18:1 as major components and C10:0 3-OH, C12:0 and C12:0 3-OH as minor components. The name Marinomonas spartinae sp. nov. is proposed, with SMJ19T (=CECT 8886T=KCTC 42958T) as the type strain. PMID- 26821808 TI - Development and use of a research productivity assessment tool for clinicians in low-resource settings in the Pacific Islands: a Delphi study. AB - BACKGROUND: Research performance assessments have proliferated, but research indicators for use amongst clinicians in poorly resourced countries have been ill defined. The aims of the present paper were to determine a set of indicators as determined by clinician participants from the Pacific Islands and a panel of research experts for use in the performance assessment of clinicians. METHODS: Two focus group discussions, one for nurses and one for doctors, were used to obtain the views of 28 Pacific Island clinicians of the BRRACAP Study about what the research indicators should be. A modified Delphi survey was used to obtain a consensus amongst 19 research experts, with Pacific Island research experience, as to what the indicators should be and then to rank these in terms of importance. A survey of the participants obtained data on the research tasks/actions performed 20 months after the initial research workshop. A resultant tool comprising of 21 indicators was used to assess the performance of 18 Pacific participants. RESULTS: The Pacific Island clinicians determined that research was important and that performance should be measured. They identified research indicators that could be used in their settings and ranked their importance using a points system. The panel of experts identified implementation of research findings, collaborations and actual change in practice as more important, with bibliometric measurements low down in the scale. Although only 64% of the 28 BRRACAP Study participants returned the questionnaire, 39% of those performed more than half of the 21 indicators used. Of the 18 Pacific clinicians assessed, 7 (39%) performed 10 or more tasks. CONCLUSIONS: A research performance assessment tool was developed using process and output indicators identified by Pacific clinicians and a panel of research experts. The tool, which placed emphasis on process and outputs that were not bibliometric based, proved useful in assessing the performance of Pacific clinicians working in a low-resource setting. PMID- 26821805 TI - Nice to meet you: genetic, epigenetic and metabolic controls of plant perception of beneficial associative and endophytic diazotrophic bacteria in non-leguminous plants. AB - A wide range of rhizosphere diazotrophic bacteria are able to establish beneficial associations with plants, being able to associate to root surfaces or even endophytically colonize plant tissues. In common, both associative and endophytic types of colonization can result in beneficial outcomes to the plant leading to plant growth promotion, as well as increase in tolerance against biotic and abiotic stresses. An intriguing question in such associations is how plant cell surface perceives signals from other living organisms, thus sorting pathogens from beneficial ones, to transduce this information and activate proper responses that will finally culminate in plant adaptations to optimize their growth rates. This review focuses on the recent advances in the understanding of genetic and epigenetic controls of plant-bacteria signaling and recognition during beneficial associations with associative and endophytic diazotrophic bacteria. Finally, we propose that "soil-rhizosphere-rhizoplane-endophytes-plant" could be considered as a single coordinated unit with dynamic components that integrate the plant with the environment to generate adaptive responses in plants to improve growth. The homeostasis of the whole system should recruit different levels of regulation, and recognition between the parties in a given environment might be one of the crucial factors coordinating these adaptive plant responses. PMID- 26821807 TI - Determinants of frequent attendance in Danish general practice: a cohort-based cross-sectional study. AB - BACKGROUND: Previous studies addressing determinants of frequent attendance have mainly focused on socio-demographic, psychosocial and medical factors, and few had data on lifestyle and gender-specific factors. This study aims to describe determinants of general practice frequent attendance in Danish adult population, by examining lifestyle, socio-demographic, medical and gender-specific factors. METHOD: For 54,849 participants of the Danish Diet, Cancer and Health cohort (50 65 year old) we obtained data on visits to general practitioner (GP) from the Danish National Health Service Register at cohort baseline (1993-97), when information on medical conditions and lifestyle, socio-demographic and gender specific factors was collected by questionnaire. Logistic regression was used to identify determinants of frequent attendance, defined as top 10% GP users at the year of recruitment into the cohort (baseline) in the period between 1993 and 1997. RESULTS: Frequent attenders accounted for 40% of all face-to-face GP consultations with a mean 12 visits/year. Women were more likely to be frequent attenders, in crude (Odds ratio: 1.95; 95% Confidence Interval: 1.85-2.06) and fully adjusted (1.26; 1.09-1.47) model. In a fully adjusted model, strongest determinants of frequent attendance were pre-existing medical conditions, with hypertension (2.58; 2.42-2.75), diabetes (2.24; 1.94-2.59), and mental illness (2.29; 2.09-2.52) more than doubling the odds of being FA. High education (0.63; 0.57-0.69, >4 years higher education vs. no vocational training) and employment (0.61; 0.57-0.65) were inversely associated with frequent attendance. Finally, obesity (1.54; 1.14-2.08), smoking (1.21; 1.12-1.30, current vs. never), physical activity (0.84; 0.80-89), alcohol consumption (0.83; 0.78-0.87 above vs. below recommended level), and hormone therapy in women (1.52; 1.42-1.63) were all significant determinants of frequent attendance. CONCLUSIONS: In addition to pre existing medical conditions, gender, socio-demographic and gender-specific factors, lifestyle (obesity, smoking, exercise and alcohol use) is also an independent determinant of frequent attendance at general practitioner. PMID- 26821809 TI - Comparison of the short form-12 (SF-12) health status questionnaire with the SF 36 in patients with knee osteoarthritis who have replacement surgery. AB - PURPOSE: To investigate whether the performance of the short form-12 (SF-12) health survey is comparable with the longer version SF-36 for measuring health related quality of life over time in patients with knee osteoarthritis who have joint replacement surgery. METHODS: Four hundred and seven patients with knee osteoarthritis completed the SF-36 before surgery and at a minimum of 12 months following knee replacement. SF-12 item responses were obtained from the responses given to the SF-36 questionnaire. Correlation coefficients were calculated between SF-12 and SF-36 physical component summary (PCS) and mental component summary (MCS) scores and the respective change in scores. Sensitivity to change was determined with the standardised response mean (SRM). RESULTS: PCS and MCS scores were highly correlated between SF-12 and SF-36 versions for both preoperative and post-operative measures (r = 0.90-0.96, p < 0.0001). Change scores (post-operative-preoperative) were also highly correlated (PCS: r = 0.88, p < 0.001; MCS: r = 0.93, p < 0.001). Sensitivity to change was large for the PCS scale (all SRMs >1.0). Correlations above 0.7 were found between change scores for each SF-36 and SF-12 subscale except General Health (r = 0.55). CONCLUSIONS: The SF-12 summary measures and component scores replicate well with the SF-36 and show similar responsiveness to change. The SF-12 appears to be an adequate alternative for use in patients with knee osteoarthritis who undergo replacement surgery, and its brevity should be attractive for both clinicians and patients. LEVEL OF EVIDENCE: I. PMID- 26821811 TI - Ecological Momentary Assessment is a Neglected Methodology in Suicidology. AB - Ecological momentary assessment (EMA) is a group of research methods that collect data frequently, in many contexts, and in real-world settings. EMA has been fairly neglected in suicidology. The current article provides an overview of EMA for suicidologists including definitions, data collection considerations, and different sampling strategies. Next, the benefits of EMA in suicidology (i.e., reduced recall bias, accurate tracking of fluctuating variables, testing assumptions of theories, use in interventions), participant safety considerations, and examples of published research that investigate self-directed violence variables using EMA are discussed. The article concludes with a summary and suggested directions for EMA research in suicidology with the particular aim to spur the increased use of this methodology among suicidologists. PMID- 26821810 TI - The effects of URAT1/SLC22A12 nonfunctional variants, R90H and W258X, on serum uric acid levels and gout/hyperuricemia progression. AB - Urate transporter 1 (URAT1/SLC22A12), a urate transporter gene, is a causative gene for renal hypouricemia type 1. Among several reported nonsynonymous URAT1 variants, R90H (rs121907896) and W258X (rs121907892) are frequent causative mutations for renal hypouricemia. However, no case-control study has evaluated the relationship between gout and these two variants. Additionally, the effect size of these two variants on serum uric acid (SUA) levels remains to be clarified. Here, 1,993 primary gout patients and 4,902 health examination participants (3,305 males and 1,597 females) were genotyped with R90H and W258X. These URAT1 variants were not observed in any gout cases, while 174 subjects had the URAT1 variant in 2,499 health examination participants, respectively (P = 8.3 * 10(-46)). Moreover, in 4,902 health examination participants, the URAT1 nonfunctional variants significantly reduce the risk of hyperuricemia (P = 6.7 * 10(-19); risk ratio = 0.036 in males). Males, having 1 or 2 nonfunctional variants of URAT1, show a marked decrease of 2.19 or 5.42 mg/dl SUA, respectively. Similarly, females, having 1 or 2 nonfunctional variants, also evidence a decrease of 1.08 or 3.89 mg/dl SUA, respectively. We show that URAT1 nonfunctional variants are protective genetic factors for gout/hyperuricemia, and also demonstrated the sex-dependent effect size of these URAT1 variants on SUA (P for interaction = 1.5 * 10(-12)). PMID- 26821812 TI - Crim1 has cell-autonomous and paracrine roles during embryonic heart development. AB - The epicardium has a critical role during embryonic development, contributing epicardium-derived lineages to the heart, as well as providing regulatory and trophic signals necessary for myocardial development. Crim1 is a unique trans membrane protein expressed by epicardial and epicardially-derived cells but its role in cardiogenesis is unknown. Using knockout mouse models, we observe that loss of Crim1 leads to congenital heart defects including epicardial defects and hypoplastic ventricular compact myocardium. Epicardium-restricted deletion of Crim1 results in increased epithelial-to-mesenchymal transition and invasion of the myocardium in vivo, and an increased migration of primary epicardial cells. Furthermore, Crim1 appears to be necessary for the proliferation of epicardium derived cells (EPDCs) and for their subsequent differentiation into cardiac fibroblasts. It is also required for normal levels of cardiomyocyte proliferation and apoptosis, consistent with a role in regulating epicardium-derived trophic factors that act on the myocardium. Mechanistically, Crim1 may also modulate key developmentally expressed growth factors such as TGFbetas, as changes in the downstream effectors phospho-SMAD2 and phospho-ERK1/2 are observed in the absence of Crim1. Collectively, our data demonstrates that Crim1 is essential for cell autonomous and paracrine aspects of heart development. PMID- 26821813 TI - Identification of new heading date determinants in wheat 5B chromosome. AB - BACKGROUND: Variability of heading date may assist in wheat adaptation to local environments. Thereafter, discovery of new heading date determinants is important for cereal improvement. In this study we used common wheat cultivar Chinese Spring (CS) and the substitution line of CS with 5B chromosome from T. dicoccoides (CS-5Bdic), different in their heading date by two weeks, to detect determinants of heading date on 5B chromosome. RESULTS: The possible influence of the VRN-B1 gene, the most powerful regulator of flowering, located on 5B chromosome, to differences in heading time between CS and CS-5Bdic was studied. The sequencing of this gene from CS-5Bdic showed that an insertion of a nucleotide triplet produced an additional amino acid in the corresponding protein. No changes in the transcription levels of each homoeologous VRN-1 loci were found in CS-5Bdic by comparison with CS. To ascertain the loci determining heading date difference, a set of 116 recombinant inbred 5V chromosomal lines as a result of hybridization of CS with CS-5Bdic were developed and their heading dates were estimated. Using the Illumina Infinium 15 k Wheat platform, 379 5B specific polymorphic markers were detected and a genetic map with 82 skeletal markers was constructed. Phenotype (heading date) - genotype association analysis revealed seventy eight markers in pericentromeric region of 5B chromosome significantly associated with heading date variation. Based on this estimation and synteny with model crop genomes we identified the three best candidate genes: WRKY, ERF/AP2 and FHY3/FAR1. CONCLUSIONS: We supposed that the difference in activity of WRKY, ERF/AP2 and/or FHY3/FAR1 transcription factors between CS and CS-5Bdic to be a probable reason for the observed difference in heading dates. Data obtained in this study provide a good basis for the subsequent investigation of heading time pathways in wheat. PMID- 26821814 TI - Host response to Staphylococcus aureus cytotoxins in children with cystic fibrosis. AB - BACKGROUND: Staphylococcus aureus is one of the earliest bacterial pathogens to colonize the lungs of children with cystic fibrosis and is an important contributor to pulmonary exacerbations. The adaptive host response to S. aureus in cystic fibrosis remains inadequately defined and has important implications for pathogenesis and potential interventions. The objectives of this study were to determine the functional antibody response to select staphylococcal exotoxins (LukAB, alpha-hemolysin, and PVL) in children with cystic fibrosis and to evaluate the relationship of this response with pulmonary exacerbations. METHODS: Fifty children with cystic fibrosis were enrolled and followed prospectively for 12months. Clinical characteristics and serologic profiles were assessed at routine visits and during pulmonary exacerbations, and functional antibody assessments were performed to measure neutralization of LukAB-mediated cytotoxicity. RESULTS: For each antigen, geometric mean titers were significantly higher if S. aureus was detected at the time of exacerbation. For LukAB, geometric mean titers were significantly higher at exacerbation follow-up compared to titers during the exacerbation, consistent with expression during human disease, and the humoral response capably neutralized LukAB-mediated cytotoxicity. Moreover, the presence of a positive S. aureus culture during a pulmonary exacerbation was associated with 31-fold higher odds of having a LukA titer >=1:160, suggesting potential diagnostic capability of this assay. CONCLUSIONS: The leukotoxin LukAB is expressed by S. aureus and recognized by the human adaptive immune response in the setting of pulmonary infection in cystic fibrosis. Anti-LukAB antibodies were not only predictive of positive staphylococcal culture during exacerbation, but also functional in the neutralization of this toxin. PMID- 26821817 TI - Reexamination of mood-mediation hypothesis of background-music-dependent effects in free recall. AB - The present study reexamined the mood-mediation hypothesis for explaining background-music-dependent effects in free recall. Experiments 1 and 2 respectively examined tempo- and tonality-dependent effects in free recall, which had been used as evidence for the mood-mediation hypothesis. In Experiments 1 and 2, undergraduates (n = 75 per experiment) incidentally learned a list of 20 unrelated words presented one by one at a rate of 5 s per word and then received a 30-s delayed oral free-recall test. Throughout the study and test sessions, a piece of music was played. At the time of test, one third of the participants received the same piece of music with the same tempo or tonality as at study, one third heard a different piece with the same tempo or tonality, and one third heard a different piece with a different tempo or tonality. Note that the condition of the same piece with a different tempo or tonality was excluded. Furthermore, the number of sampled pieces of background music was increased compared with previous studies. The results showed neither tempo- nor tonality dependent effects, but only a background-music-dependent effect. Experiment 3 (n = 40) compared the effects of background music with a verbal association task and focal music (only listening to musical selections) on the participants' moods. The results showed that both the music tempo and tonality influenced the corresponding mood dimensions (arousal and pleasantness). These results are taken as evidence against the mood-mediation hypothesis. Theoretical implications are discussed. PMID- 26821816 TI - Reduction of aberrant NF-kappaB signalling ameliorates Rett syndrome phenotypes in Mecp2-null mice. AB - Mutations in the transcriptional regulator Mecp2 cause the severe X-linked neurodevelopmental disorder Rett syndrome (RTT). In this study, we investigate genes that function downstream of MeCP2 in cerebral cortex circuitry, and identify upregulation of Irak1, a central component of the NF-kappaB pathway. We show that overexpression of Irak1 mimics the reduced dendritic complexity of Mecp2-null cortical callosal projection neurons (CPN), and that NF-kappaB signalling is upregulated in the cortex with Mecp2 loss-of-function. Strikingly, we find that genetically reducing NF-kappaB signalling in Mecp2-null mice not only ameliorates CPN dendritic complexity but also substantially extends their normally shortened lifespan, indicating broader roles for NF-kappaB signalling in RTT pathogenesis. These results provide new insight into both the fundamental neurobiology of RTT, and potential therapeutic strategies via NF-kappaB pathway modulation. PMID- 26821818 TI - Inhibition of monoamine oxidase by benzoxathiolone analogues. AB - Inhibitors of the monoamine oxidase (MAO) enzymes are considered useful therapeutic agents, and are used in the clinic for the treatment of depressive illness and Parkinson's disease. In addition, MAO inhibitors are also under investigation for the treatment of certain cardiovascular pathologies and as possible aids to smoking cessation. In an attempt to discover novel classes of compounds that inhibit the MAOs, the current study examines the human MAO inhibitory properties of a small series of 2H-1,3-benzoxathiol-2-one analogues. The results show that the benzoxathiolones are potent MAO-B inhibitors with IC50 values ranging from 0.003 to 0.051 MUM. Although the benzoxathiolones are selective for the MAO-B isoform, two compounds display good MAO-A inhibition with IC50 values of 0.189 and 0.424 MUM. Dialysis studies show that a selected compound inhibits the MAOs reversibly. It may thus be concluded that the benzoxathiolone class is suitable for the design and development of MAO-B inhibitors, and that in some instances good MAO-A inhibition may also be achieved. PMID- 26821815 TI - Chemokine and chemokine receptors in autoimmunity: the case of primary biliary cholangitis. AB - Chemokines represent a major mediator of innate immunity and play a key role in the selective recruitment of cells during localized inflammatory responses. Beyond critical extracellular mediators of leukocyte trafficking, chemokines and their cognate receptors are expressed by a variety of resident and infiltrating cells (monocytes, lymphocytes, NK cells, mast cells, and NKT cells). Chemokines represent ideal candidates for mechanistic studies (particularly in murine models) to better understand the pathogenesis of chronic inflammation and possibly become biomarkers of disease. Nonetheless, therapeutic approaches targeting chemokines have led to unsatisfactory results in rheumatoid arthritis, while biologics against pro-inflammatory cytokines are being used worldwide with success. In this comprehensive review we will discuss the evidence supporting the involvement of chemokines and their specific receptors in mediating the effector cell response, utilizing the autoimmune/primary biliary cholangitis setting as a paradigm. PMID- 26821819 TI - 4H-Thieno[3,2-c]chromene based inhibitors of Notum Pectinacetylesterase. AB - A group of small molecule thienochromenes inhibitors of Notum Pectinacetylesterase are described. We developed SAR on three series based on carbon, oxygen and sulfur replacement of the 5-position. In each series, highly potent Notum Pectinacetylesterase inhibitors were identified. PMID- 26821820 TI - Gibbilimbol analogues as antiparasitic agents--Synthesis and biological activity against Trypanosoma cruzi and Leishmania (L.) infantum. AB - The essential oils from leaves of Piper malacophyllum (Piperaceae) showed to be mainly composed by two alkenylphenol derivatives: gibbilimbols A and B. After isolation and structural characterization by NMR and MS data analysis, both compounds were evaluated against promastigote/amastigote forms of Leishmania (L.) infantum as well as trypomastigote/amastigote forms of Trypanosoma cruzi. The obtained results indicated that gibbilimbol B displayed potential against the tested parasites and low toxicity to mammalian cells, stimulating the preparation of several quite simple synthetic analogues in order to improve its activity and to explore the preliminary structure-activity relationships (SAR) data. Among the prepared derivatives, compound LINS03003 (n-octyl-4-hydroxybenzylamine) displayed the most potent IC50 values of 5.5 and 1.8 MUM against amastigotes of T. cruzi and L. (L.) infantum, respectively, indicating higher activity than the natural prototype. In addition, this compound showed remarkable selectivity index (SI) towards the intracellular forms of Leishmania (SI=13.1) and T. cruzi (SI=4.3). Therefore, this work indicated that preparation of synthetic compounds structurally based in the bioactive natural products could be an interesting source of novel and selective compounds against these protozoan parasites. PMID- 26821821 TI - Discovery of spirocyclic proline tryptophan hydroxylase-1 inhibitors. AB - The central role of the biogenic monoamine serotonin (5-hydroxytryptamine, 5-HT) as a neurotransmitter with important cognitive and behavioral functions is well known. However, 5-HT produced in the brain only accounts for approximately 5% of the total amount of 5-HT generated in the body. At the onset of our work, it appeared that substituted phenylalanine derivatives or related aryl amino acids were required to produce potent inhibitors of TPH1, as significant losses of inhibitory activity were noted in the absence of this structural element. We disclose herein the discovery of a new class of TPH1 inhibitors that significantly lower peripherally 5-HT. PMID- 26821822 TI - Polymerase recognition of 2-thio-iso-guanine.5-methyl-4-pyrimidinone (iGs.P)--A new DD/AA base pair. AB - Polymerase specificity is reported for a previously unknown base pair with a non standard DD/AA hydrogen bonding pattern: 2-thio-iso-guanine.5-methyl-4 pyrimidinone. Our findings suggest that atomic substitution may provide a solution for low fidelity previously associated with enzymatic copying of iso guanine. PMID- 26821823 TI - Effects of low speed wind on the recognition/identification and pass-through communication tasks of auditory situation awareness afforded by military hearing protection/enhancement devices and tactical communication and protective systems. AB - OBJECTIVE: To investigate the effect of controlled low-speed wind-noise on the auditory situation awareness performance afforded by military hearing protection/enhancement devices (HPED) and tactical communication and protective systems (TCAPS). DESIGN: Recognition/identification and pass-through communications tasks were separately conducted under three wind conditions (0, 5, and 10 mph). Subjects wore two in-ear-type TCAPS, one earmuff-type TCAPS, a Combat Arms Earplug in its 'open' or pass-through setting, and an EB-15LE electronic earplug. Devices with electronic gain systems were tested under two gain settings: 'unity' and 'max'. Testing without any device (open ear) was conducted as a control. STUDY SAMPLE: Ten subjects were recruited from the student population at Virginia Tech. Audiometric requirements were 25 dBHL or better at 500, 1000, 2000, 4000, and 8000 Hz in both ears. RESULTS: Performance on the interaction of communication task-by-device was significantly different only in 0 mph wind speed. The between-device performance differences varied with azimuthal speaker locations. CONCLUSIONS: It is evident from this study that stable (non-gusting) wind speeds up to 10 mph did not significantly degrade recognition/identification task performance and pass-through communication performance of the group of HPEDs and TCAPS tested. However, the various devices performed differently as the test sound signal speaker location was varied and it appears that physical as well as electronic features may have contributed to this directional result. PMID- 26821824 TI - Spatially resolved and orientation dependent Raman mapping of epitaxial lateral overgrowth nonpolar a-plane GaN on r-plane sapphire. AB - Uncoalesced a-plane GaN epitaxial lateral overgrowth (ELO) structures have been synthesized along two mask stripe orientations on a-plane GaN template by MOCVD. The morphology of two ELO GaN structures is performed by Scanning electronic microscopy. The anisotropy of crystalline quality and stress are investigated by micro-Raman spectroscopy. According to the Raman mapping spectra, the variations on the intensity, peak shift and the full width at half maximum (FWHM) of GaN E2 (high) peak indicate that the crystalline quality improvement occurs in the window region of the GaN stripes along [0001], which is caused by the dislocations bending towards the sidewalls. Conversely, the wing regions have better quality with less stress as the dislocations propagated upwards when the GaN stripes are along []. Spatial cathodoluminescence mapping results further support the explanation for the different dislocation growth mechanisms in the ELO processes with two different mask stripe orientations. PMID- 26821825 TI - Process development of a New Haemophilus influenzae type b conjugate vaccine and the use of mathematical modeling to identify process optimization possibilities. AB - Vaccination is one of the most successful public health interventions being a cost-effective tool in preventing deaths among young children. The earliest vaccines were developed following empirical methods, creating vaccines by trial and error. New process development tools, for example mathematical modeling, as well as new regulatory initiatives requiring better understanding of both the product and the process are being applied to well-characterized biopharmaceuticals (for example recombinant proteins). The vaccine industry is still running behind in comparison to these industries. A production process for a new Haemophilus influenzae type b (Hib) conjugate vaccine, including related quality control (QC) tests, was developed and transferred to a number of emerging vaccine manufacturers. This contributed to a sustainable global supply of affordable Hib conjugate vaccines, as illustrated by the market launch of the first Hib vaccine based on this technology in 2007 and concomitant price reduction of Hib vaccines. This paper describes the development approach followed for this Hib conjugate vaccine as well as the mathematical modeling tool applied recently in order to indicate options for further improvements of the initial Hib process. The strategy followed during the process development of this Hib conjugate vaccine was a targeted and integrated approach based on prior knowledge and experience with similar products using multi-disciplinary expertise. Mathematical modeling was used to develop a predictive model for the initial Hib process (the 'baseline' model) as well as an 'optimized' model, by proposing a number of process changes which could lead to further reduction in price. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:568-580, 2016. PMID- 26821828 TI - Photothermoelectric Effects in Nanoporous Silicon. AB - The first observation of the photothermoelectric effect in a nanoporous silicon (NPSi) device indicates that the photocurrent is dependent on the position of light-induced local heating from illumination at the Au-electrode/NPSi interface. PMID- 26821829 TI - General practice being "eroded" in Scotland, says RCGP. PMID- 26821826 TI - Normothermic Mouse Functional MRI of Acute Focal Thermostimulation for Probing Nociception. AB - Combining mouse genomics and functional magnetic resonance imaging (fMRI) provides a promising tool to unravel the molecular mechanisms of chronic pain. Probing murine nociception via the blood oxygenation level-dependent (BOLD) effect is still challenging due to methodological constraints. Here we report on the reproducible application of acute noxious heat stimuli to examine the feasibility and limitations of functional brain mapping for central pain processing in mice. Recent technical and procedural advances were applied for enhanced BOLD signal detection and a tight control of physiological parameters. The latter includes the development of a novel mouse cradle designed to maintain whole-body normothermia in anesthetized mice during fMRI in a way that reflects the thermal status of awake, resting mice. Applying mild noxious heat stimuli to wildtype mice resulted in highly significant BOLD patterns in anatomical brain structures forming the pain matrix, which comprise temporal signal intensity changes of up to 6% magnitude. We also observed sub-threshold correlation patterns in large areas of the brain, as well as alterations in mean arterial blood pressure (MABP) in response to the applied stimulus. PMID- 26821827 TI - A novel NF-kappaB/YY1/microRNA-10a regulatory circuit in fibroblast-like synoviocytes regulates inflammation in rheumatoid arthritis. AB - The main etiopathogenesis of rheumatoid arthritis (RA) is overexpressed inflammatory cytokines and tissue injury mediated by persistent NF-kappaB activation. MicroRNAs widely participate in the regulation of target gene expression and play important roles in various diseases. Here, we explored the mechanisms of microRNAs in RA. We found that microRNA (miR)-10a was downregulated in the fibroblast-like synoviocytes (FLSs) of RA patients compared with osteoarthritis (OA) controls, and this downregulation could be triggered by TNF alpha and IL-1beta in an NF-kappaB-dependent manner through promoting the expression of the YingYang 1 (YY1) transcription factor. Downregulated miR-10a could accelerate IkappaB degradation and NF-kappaB activation by targeting IRAK4, TAK1 and BTRC. This miR-10a-mediated NF-kappaB activation then significantly promoted the production of various inflammatory cytokines, including TNF-alpha, IL-1beta, IL-6, IL-8, and MCP-1, and matrix metalloproteinase (MMP)-1 and MMP-13. In addition, transfection of a miR-10a inhibitor accelerated the proliferation and migration of FLSs. Collectively, our data demonstrates the existence of a novel NF-kappaB/YY1/miR-10a/NF-kappaB regulatory circuit that promotes the excessive secretion of NF-kappaB-mediated inflammatory cytokines and the proliferation and migration of RA FLSs. Thus, miR-10a acts as a switch to control this regulatory circuit and may serve as a diagnostic and therapeutic target for RA treatment. PMID- 26821830 TI - Why Is MP2-Water "Cooler" and "Denser" than DFT-Water? AB - Density functional theory (DFT) with a dispersionless generalized gradient approximation (GGA) needs much higher temperature and pressure than the ambient conditions to maintain water in the liquid phase at the correct (1 g/cm(3)) density during first-principles simulations. Conversely, ab initio second-order many-body perturbation (MP2) calculations of liquid water require lower temperature and pressure than DFT/GGA to keep water liquid. Here we present a unifying explanation of these trends derived from classical water simulations using a polarizable force field with different sets of parameters. We show that the different temperatures and pressures between DFT/GGA and MP2 at which the simulated water displays the experimentally observed liquid structure under the ambient conditions can be largely explained by their differences in polarizability and dispersion interaction, respectively. In DFT/GGA, the polarizability and thus the induced dipole moments and the hydrogen-bond strength are all overestimated. This hinders the rotational motion of molecules and requires a higher temperature for DFT-water to be liquid. MP2 gives a stronger dispersion interaction and thus shorter intermolecular distances than dispersionless DFT/GGA, which is why MP2-water is denser than DFT-water under the same external pressure. PMID- 26821831 TI - Probing the quaternary structure of metal-bridged peptide oligomers. AB - The oligomerisation of many proteins and peptides is known to be influenced by the binding of transition metal ions such as divalent copper. To investigate the oligomeric state of model peptides related to the N-terminus of alpha-synuclein (alphaSyn) in the presence of Cu(II), electron paramagnetic resonance (EPR) spectroscopy and isotopic labelling were recently used to conclude that Cu(II) occupies N-terminal bridging positions within closed-chain alphaSyn dimers and trimers with a Cu/peptide stoichiometry of 1:1. Herein, a statistical correction is identified and the consequences are evaluated. The analysis reveals that alphaSyn forms Cu-bridged antiparallel dimers and closed-chain trimers that coexist with Cu(II)-bound monomers (including a "macrochelate") and, depending on metal stoichiometry and protein environment, with open-chain Cu-bridged oligomers and heterodimers. The results demonstrate that the Cu(II) ion can be exploited as a probe of protein quaternary structure, with the potential to delineate heterogeneous oligomeric populations. PMID- 26821832 TI - EPR spectroscopic characterization of a monomeric PtIII species produced via electrochemical oxidation of the anticancer compound trans-[PtII{(p HC6F4)NCH2CH2NEt2}Cl(py)]. AB - The bulk oxidative electrolysis of a 2mM solution of trans-[PtII{(p HC6F4)NCH2CH2NEt2}Cl(py)] in highly non-coordinating dichloromethane (0.05M [Bu4N][B(C6F5)]) media leads to the formation of about 14% of the PtIII species trans-[PtIII{(p-HC6F4)NCH2CH2NEt2}Cl(py)]+. The EPR spectrum of this electro synthesized formally PtIII species shows Pt-hyperfine coupling with gx~gy>gz~ge, and is broadly consistent with the simple crystal field theory prediction for 5d7 PtIII in an elongated tetragonal environment where the unpaired electron is in a 5d(z2) orbital. The crystal field calculations lead to an estimate of the 5d(z2) character of around 37% and indicate partial delocalization of the unpaired electron onto the orbitals of the surrounding ligands. Transient cyclic voltammetric and steady-state microelectrode studies in the same media as used for bulk electrolysis exhibit a chemically reversible one electron oxidation process under their shorter time scale conditions. Analysis of X-ray diffraction data obtained from a single crystal of trans-[PtII{(p-HC6F4)NCH2CH2NEt2}Cl(py)] shows the square planar geometry of the ligands around the Pt metal center and the 'W' arrangement of the ethyl groups on the ligand is explained in terms of agostic interactions. PMID- 26821833 TI - An Evidence-Based Approach to Scoping Reviews. AB - OBJECTIVE: Scoping reviews are used to assess the extent of a body of literature on a particular topic, and often to ensure that further research in that area is a beneficial addition to world knowledge. The aim of this paper reports upon the development of a methodology for scoping reviews based upon the Arksey and O'Malley framework, the Levac, Colquhoun, and O'Brien, and the Joanna Briggs Institute methods of evidence synthesis. METHODS: A working group consisting of members of the Joanna Briggs collaborating organizations met to discuss the proposed framework for the methodology and develop a draft for the scoping review methodology based on the Arksey and O'Malley framework and the work of Levac et al. This was followed by a workshop attended by other members of the organizations consisting of 30 international researchers to discuss the proposed methodology. Further refinement of the methodology was undertaken as a result of the feedback received from the workshop. RESULTS: The development of the methodology focused on five stages of the protocol and review development. These were identifying the research question by clarifying and linking the purpose and research question, identifying the relevant studies using a three-step literature search in order to balance feasibility with breadth and comprehensiveness, careful selection of the studies to using a team approach, charting the data and collating the results to identify the implications of the study findings for policy, practice, or research. LINKING EVIDENCE TO ACTION: The current methodology recommends including both quantitative and qualitative research, as well as evidence from economic and expert opinion sources to answer questions of effectiveness, appropriateness, meaningfulness and feasibility of health practices and delivery methods. The proposed framework has the potential to provide options when faced with complex concepts or broad research questions. PMID- 26821834 TI - Frequency of E-Cigarette Use and Cigarette Smoking by American Students in 2014. AB - INTRODUCTION: High school students' electronic cigarette (e-cigarette) use rose rapidly in 2014, to levels higher than cigarette smoking, which declined significantly. This study assesses how frequency of e-cigarette use is associated with students' smoking status. METHODS: Using Monitoring the Future data in 2015, this study evaluated the association between students' smoking and frequency of 30-day e-cigarette use in 2014, focusing on high school seniors. Previous research has considered only whether e-cigarettes were used at all during the past month. RESULTS: Non-smokers were far less likely than smokers to have used an e-cigarette (p<0.001). E-cigarette use frequency rose with the amount of ever smoking (p<0.001). However, among current smokers, there was no difference in e cigarette use by very light smokers (<1 cigarette/day); light smokers (1-5 cigarettes/day); and heavy smokers (>=1/2 pack/day) (p=0.99). Because most students have never smoked, never smokers constituted 25% of all seniors who used an e-cigarette. Among tenth- and eighth-graders, 43% and 48% of past-month e cigarette users had never smoked. CONCLUSIONS: Non-smoking high school students are highly unlikely to use e-cigarettes; among those who do, most used them only on 1-2 of the past 30 days. By contrast, current smokers are likely to use e cigarettes and on many more days. It is unclear whether students' e-cigarette use represents short-term experimentation or future sustained use, and whether it will eventually increase or decrease youth smoking and nicotine addiction. More sophisticated research methods, employing better data, will be essential to unravel the mystery that is the e-cigarette phenomenon. PMID- 26821836 TI - Assessing size of pituitary adenomas: a comparison of qualitative and quantitative methods on MR. AB - BACKGROUND: A variety of methods are used for estimating pituitary tumour size in clinical practice and in research. Quantitative methods, such as maximum tumour dimension, and qualitative methods, such as Hardy and Knosp grades, are well established but do not give an accurate assessment of the tumour volume. We therefore sought to compare existing measures of pituitary tumours with more quantitative methods of tumour volume estimation. METHOD: Magnetic resonance imaging was reviewed for 99 consecutive patients with pituitary adenomas awaiting surgery between 2010 and 2013. Maximal tumour diameter, Hardy and Knosp grades were compared with tumour volume estimates by the ellipsoid equation, [4/3pi (a,b,c)], (i.e. ellipsoid volume) and slice-by-slice perimetry (i.e. perimeter volume). RESULTS: Ellipsoid and perimeter methods of tumour volume estimation strongly correlated (R(2) = 0.99, p < 0.0001). However the correlation was less strong with increasing tumour size, with the ellipsoid method slightly underestimating. The mean differences were -0.11 (95 % CI, -0.35, 0.14), -0.74 (95 % CI, -2.2, 0.74) and -1.4 (95 % CI, -6.4, 3.7) for micro-tumours, macro tumours and giant tumours respectively. Tumour volume correlated with maximal diameter, following a cubic distribution. Correlations of tumour volume with Hardy and Knosp grades was less strong. CONCLUSIONS: Perimeter and ellipsoid methods give a good estimation of tumour volume, whereas Knosp and Hardy grades may offer other clinically relevant information, such as cavernous sinus invasion or chiasmal compression. Thus the different methods of estimating tumour size are likely to have different clinical utilities. PMID- 26821837 TI - Vertebral artery dolicoectasia with brainstem compression: role of microvascular decompression in relieving pyramidal weakness. AB - Vertebral artery dolicoectasia (VAD) can cause brainstem compression and dysfunction. Reports of pyramidal tract involvement by brainstem compression and the surgical benefits and its long-term results are sparsely reported. We hereby report three cases of medullary compression by VAD causing pyramidal weakness. Two patients with bilateral compression with quadriparesis did not want surgical treatment and were still disabled at 58 months and 50 months of follow-up, respectively. One patient with unilateral medullary compression with hemiparesis underwent microvascular decompression using Teflon sling retraction. This patient was relieved of symptoms and is asymptomatic at 14-month follow-up. This report emphasizes the need of surgical decompression in cases of brainstem compression by VAD with caution about appropriate case selection. PMID- 26821835 TI - Time to Osteoporosis and Major Fracture in Older Men: The MrOS Study. AB - INTRODUCTION: For older men who undergo bone mineral density (BMD) testing, the optimal osteoporosis screening schedule is unknown. Time-to-disease estimates are necessary to inform screening intervals. METHODS: A prospective cohort study of 5,415 community-dwelling men aged >=65 years without hip or clinical vertebral fracture or antifracture treatment at baseline was conducted. Participants had concurrent BMD and fracture follow-up between 2000 and 2009, and additional fracture follow-up through 2014. Data were analyzed in 2015. Time to incident osteoporosis (lowest T-score <= -2.50) for men without baseline osteoporosis, and time to hip or clinical vertebral fracture or major osteoporotic fracture for men without or with baseline osteoporosis, were estimated. RESULTS: Nine men (0.2%) with BMD T-scores >-1.50 at baseline developed osteoporosis during follow-up. The adjusted estimated time for 10% to develop osteoporosis was 8.5 (95% CI=6.7, 10.9) years for those with moderate osteopenia (lowest T-score, -1.50 to -1.99) and 2.7 (95% CI=2.1, 3.4) years for those with advanced osteopenia (lowest T score, -2.00 to -2.49) at baseline. The adjusted times for 3% to develop a first hip or clinical vertebral fracture ranged from 7.1 (95% CI=6.0, 8.3) years in men with baseline T-scores > -1.50 to 1.7 (95% CI=1.0, 3.1) years in men with baseline osteoporosis. CONCLUSIONS: Men aged 65 years and older with femoral neck, total hip, and lumbar spine BMD T-scores >-1.50 on a first BMD test were very unlikely to develop osteoporosis during follow-up. Additional BMD testing may be most informative in older men with T-scores <=-1.50. PMID- 26821838 TI - The effect of elbow hyperextension on ball speed in cricket fast bowling. AB - This study investigates how elbow hyperextension affects ball release speed in fast bowling. A two-segment planar computer simulation model comprising an upper arm and forearm + hand was customised to an elite fast bowler. A constant torque was applied at the shoulder and elbow hyperextension was represented using a damped linear torsional spring at the elbow. The magnitude of the constant shoulder torque and the torsional spring parameters were determined by concurrently matching three performances. Close agreement was found between the simulations and the performances with an average difference of 3.8%. The simulation model with these parameter values was then evaluated using one additional performance. Optimising ball speed by varying the torsional spring parameters found that elbow hyperextension increased ball release speed. Perturbing the elbow torsional spring stiffness indicated that the increase in ball release speed was governed by the magnitude of peak elbow hyperextension and the amount that the elbow recoils back towards a straight arm after reaching peak elbow hyperextension. This finding provides a clear understanding that a bowler who hyperextends at the elbow and recoils optimally will have an increase in ball speed compared to a similar bowler who cannot hyperextend. A fast bowler with 20 degrees of elbow hyperextension and an optimal level of recoil will have increased ball speeds of around 5% over a bowler without hyperextension. PMID- 26821839 TI - Official Methods for the Determination of Minerals and Trace Elements in Infant Formula and Milk Products: A Review. AB - The minerals and trace elements that account for about 4% of total human body mass serve as materials and regulators in numerous biological activities in body structure building. Infant formula and milk products are important sources of endogenic and added minerals and trace elements and hence, must comply with regulatory as well as nutritional and safety requirements. In addition, reliable analytical data are necessary to support product content and innovation, health claims, or declaration and specific safety issues. Adequate analytical platforms and methods must be implemented to demonstrate both the compliance and safety assessment of all declared and regulated minerals and trace elements, especially trace-element contaminant surveillance. The first part of this paper presents general information on the mineral composition of infant formula and milk products and their regulatory status. In the second part, a survey describes the main techniques and related current official methods determining minerals and trace elements in infant formula and milk products applied for by various international organizations (AOAC INTERNATIONAL, the International Organization for Standardization, the International Dairy Federation, and the European Committe for Standardization). The third part summarizes method officialization activities by Stakeholder Panels on Infant Formula and Adult Nutritionals and Stakeholder Panel on Strategic Food Analytical Methods. The final part covers a general discussion focusing on analytical gaps and future trends in inorganic analysis that have been applied for in infant formula and milk-based products. PMID- 26821840 TI - Psoas Muscle Area and All-Cause Mortality After Transcatheter Aortic Valve Replacement: The Montreal-Munich Study. AB - BACKGROUND: Psoas muscle area (PMA) is a novel measure of frailty that can be efficiently measured from computed tomography images to help predict risk in older adults referred for transcatheter aortic valve replacement (TAVR). The objective of this study was to determine if PMA would be incrementally predictive of mortality and morbidity after TAVR. METHODS: The pre-TAVR computed tomography scans of 208 consecutive patients at 2 hospitals in Montreal and Munich were analyzed to measure the cross-sectional area of the left and right psoas muscles on a single axial slice at the level of L4. The primary outcome was all-cause mortality assessed according to sex-stratified Cox regression models adjusted for the Society of Thoracic Surgeons predicted risk of mortality. RESULTS: The mean age was 80.7 +/- 6.8 years with 55% women and a total of 57 deaths over a mean follow-up of 504 days. PMA was lower in nonsurvivors compared with survivors among women (12.9 vs 14.5 cm(2); P = 0.047) but not men (21.7 vs 22.4 cm(2); P = 0.50). The association between PMA and all-cause mortality in women persisted after adjustment for Society of Thoracic Surgeons risk (hazard ratio, 0.88 per cm(2); 95% confidence interval, 0.78-0.99). An association between PMA and bleeding complications was seen in men (odds ratio, 0.78; 95% confidence interval, 0.62-0.97). Sensitivity analyses with PMA normalized to body mass index yielded similar results. CONCLUSIONS: This study has shown that PMA is a marker of frailty associated with midterm survival in women who undergo TAVR. Further research is warranted to pursue PMA as a prognostic marker and therapeutic target in this vulnerable population. PMID- 26821842 TI - Electrochemical telomerase assay for screening for oral cancer. AB - Telomerase has long been known to be a marker for cancer. We have developed a new method of detecting it: the electrochemical telomerase assay (ECTA). We have previously confirmed that the assay is easier to do and more precise than the conventional telomeric repeat amplification protocol, which is currently the most widely used. Here we describe a pilot study made to establish a screening system for oral cancer using ECTA. We evaluated three types of clinical samples obtained from 44 patients with oral cancer and 26 healthy volunteers: exfoliated cells from the whole oral cavity, exfoliated cells from local lesions, and tissue from the lesion itself. The current increase ratio (Deltai) obtained by ECTA was significantly higher in the oral cancer group for each type of sampling used. The threshold value for Deltai was 19% when calculated by analysis of receiver operating characteristic curves. Sensitivity and specificity values were 86% and 85% for cells from the oral cavity, 82% and 85% in cells from local lesions, and 95% and 92% in cells from the tumour itself, respectively. There were also no significant differences in sensitivity and specificity associated with age, size of tumour, site of lesion, or degree of malignancy. ECTA therefore seems to be a promising assay for screening for oral cancer. PMID- 26821841 TI - Investigation of the combined effect of MgO and PEG on the release profile of mefenamic acid prepared via hot-melt extrusion techniques. AB - This study aimed to investigate the combined effect of magnesium oxide (MgO) as an alkalizer and polyethylene glycol (PEG) as a plasticizer and wetting agent in the presence of Kollidon(r) 12 PF and 17 PF polymer carriers on the release profile of mefenamic acid (MA), which was prepared via hot-melt extrusion technique. Various drug loads of MA and various ratios of the polymers, PEG 3350 and MgO were blended using a V-shell blender and extruded using a twin-screw extruder (16-mm Prism EuroLab, ThermoFisher Scientific, Carlsbad, CA) at different screw speeds and temperatures to prepare a solid dispersion system. Differential scanning calorimetry and X-ray diffraction data of the extruded material confirmed that the drug existed in the amorphous form, as evidenced by the absence of corresponding peaks. MgO and PEG altered the micro-environmental pH to be more alkaline (pH 9) and increased the hydrophilicity and dispersibility of the extrudates to enhance MA solubility and release, respectively. The in vitro release study demonstrated an immediate release for 2 h with more than 80% drug release within 45 min in matrices containing MgO and PEG in combination with polyvinylpyrrolidone when compared to the binary mixture, physical mixture and pure drug. PMID- 26821843 TI - Angelica sinensis reduced Abeta-induced memory impairment in rats. AB - BACKGROUND: Studies have shown that Angelica sinensis (JiLin AoDong Medicine Industry Groups Co., Ltd., Jilin, China) root (AS) ameliorates various diseases, although its effects in Alzheimer's disease (AD) have not been elucidated. PURPOSE: The present study examined the effects of AS in a rat model of AD. METHODS: Positional Abeta injections were administered to rats. The behavioral effects of AS administration were examined using the Morris water maze, and the molecular effects on gene and protein expression, and apoptosis, were determined. RESULTS: AS reversed the social behavioral impairments observed in this rat model of Abeta-induced memory impairment. Western blot analysis also revealed lower hippocampal levels of Abeta and beta-site amyloid precursor protein-cleaving enzyme. Terminal deoxynucleotidyl transferased UTP nick end labeling indicated that AS significantly inhibited apoptosis via effects on nuclear factor kappa B (NF-kappaB) signaling. Real-time PCR, enzyme-linked immunosorbent assay, and immunohistochemical staining indicated that AS effectively inhibited inflammation and upregulated expression of glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) in the hippocampus of this rat AD model. DISCUSSION: AS effectively rescued the symptoms of AD in a rat model by inhibiting inflammation, apoptosis, and NF-kappaB signaling pathway. CONCLUSION: These findings suggested that AS could provide a potential drug for the treatment of AD. PMID- 26821845 TI - Successful cardiac transplantation in a patient with congenital generalized lipodystrophy. AB - We report a case of a 12-yr-old boy referred to our unit with congenital generalized lipodystrophy and dilated cardiomyopathy related to a lamin gene mutation. He progressively developed end-stage heart failure and was referred for heart transplant evaluation. The patient's lipid profile, glucose level, and renal function were normal, and vascular retinopathy was ruled out. He underwent orthotopic bicaval HT and had an uneventful recovery. He was discharged home two wk after surgery with good graft function. During follow-up, he developed hyperglycemia and dyslipidemia, which were controlled by increasing leptin dose and starting oral antidiabetic drugs. The patient is currently doing well two yr after transplantation. PMID- 26821846 TI - What happens after you submit a paper to Women and Birth: An insider's view of editorial and review processes. PMID- 26821844 TI - Histone H3K36 methylation regulates pre-mRNA splicing in Saccharomyces cerevisiae. AB - Co-transcriptional splicing takes place in the context of a highly dynamic chromatin architecture, yet the role of chromatin restructuring in coordinating transcription with RNA splicing has not been fully resolved. To further define the contribution of histone modifications to pre-mRNA splicing in Saccharomyces cerevisiae, we probed a library of histone point mutants using a reporter to monitor pre-mRNA splicing. We found that mutation of H3 lysine 36 (H3K36) - a residue methylated by Set2 during transcription elongation - exhibited phenotypes similar to those of pre-mRNA splicing mutants. We identified genetic interactions between genes encoding RNA splicing factors and genes encoding the H3K36 methyltransferase Set2 and the demethylase Jhd1 as well as point mutations of H3K36 that block methylation. Consistent with the genetic interactions, deletion of SET2, mutations modifying the catalytic activity of Set2 or H3K36 point mutations significantly altered expression of our reporter and reduced splicing of endogenous introns. These effects were dependent on the association of Set2 with RNA polymerase II and H3K36 dimethylation. Additionally, we found that deletion of SET2 reduces the association of the U2 and U5 snRNPs with chromatin. Thus, our study provides the first evidence that H3K36 methylation plays a role in co-transcriptional RNA splicing in yeast. PMID- 26821847 TI - Intrinsic functional connectivity of periaqueductal gray subregions in humans. AB - The periaqueductal gray matter (PAG) is a key brain region of the descending pain modulation pathway. It is also involved in cardiovascular functions, anxiety, and fear; however, little is known about PAG subdivisions in humans. The aims of this study were to use resting-state fMRI-based functional connectivity (FC) to parcellate the human PAG and to determine FC of its subregions. To do this, we acquired resting-state fMRI scans from 79 healthy subjects and (1) used a data driven method to parcellate the PAG, (2) used predefined seeds in PAG subregions to evaluate PAG FC to the whole brain, and (3) examined sex differences in PAG FC. We found that clustering of the left and right PAG yielded similar patterns of caudal, middle, and rostral subdivisions in the coronal plane, and dorsal and ventral subdivisions in the sagittal plane. FC analysis of predefined subregions revealed that the ventolateral(VL)-PAG was supfunctionally connected to brain regions associated with descending pain modulation (anterior cingulate cortex (ACC), upper pons/medulla), whereas the lateral (L) and dorsolateral (DL) subregions were connected with brain regions implicated in executive functions (prefrontal cortex, striatum, hippocampus). We also found sex differences in FC including areas implicated in pain, salience, and analgesia including the ACC and the insula in women, and the MCC, parahippocampal gyrus, and the temporal pole in men. The organization of the human PAG thus provides a framework to understand the circuitry underlying the broad range of responses to pain and its modulation in men and women. PMID- 26821848 TI - "EB, or Not EB?" Neonatal Desquamative Impetigo in a Degloving Pattern. AB - We present the case of a 7-day-old boy with significant, rapidly spreading blistering and desquamation in a "degloving" pattern on the hands that mimicked epidermolysis bullosa but was ultimately diagnosed as bullous impetigo caused by a clinically aggressive strain of Staphylococcus aureus. Bullous impetigo is a desquamating condition caused by local release of S. aureus exfoliative toxin A and is more commonly seen in children. This case highlights the fragility of newborn skin and reviews the major diagnoses that should be considered in an infant with significant blistering. PMID- 26821849 TI - Structure of Amido Pyridinium Betaines: Persistent Intermolecular C-H???N Hydrogen Bonding in Solution. AB - A hydrogen bond of the type C-H???X (X=O or N) is known to influence the structure and function of chemical and biological systems in solution. C-H???O hydrogen bonding in solution has been extensively studied, both experimentally and computationally, whereas the equivalent thermodynamic parameters have not been enumerated experimentally for C-H???N hydrogen bonds. This is, in part, due to the lack of systems that exhibit persistent C-H???N hydrogen bonds in solution. Herein, a class of molecule based on a biologically active norharman motif that exhibits unsupported intermolecular C-H???N hydrogen bonds in solution has been described. A pairwise interaction leads to dimerisation to give bond strengths of about 7 kJ mol-1 per hydrogen bond, which is similar to chemically and biologically relevant C-H???O hydrogen bonding. The experimental data is supported by computational work, which provides additional insight into the hydrogen bonding by consideration of electrostatic and orbital interactions and allowed a comparison between calculated and extrapolated NMR chemical shifts. PMID- 26821851 TI - Cattell's Scree Test In Relation To Bartlett's Chi-Square Test And Other Observations On The Number Of Factors Problem. AB - It is demonstrated that Cattell's scree test and Bartlett's chi-square test for the number of factors are both based on the same rationale, so the former reflects statistical (subject sampling) variability and the latter usually involves psychometric (variable sampling) influences. If the alpha-level (implicit in the scree test) is set the same, the two tests should lead to the same conclusions. Analyses with some examples suggest that if the alpha-level for the Bartlett test is set (explicitly) in the neighborhood of .0003 for sample Ns of 100 to 150, the results from applications of this test will indicate approximately the same number of factors as estimated on the basis of a scree test determined on a much larger (N ? 600) sample. Used in this way, the Bartlett test may yield fairly good "population" estimates of the number of factors. Relationships between the Bartlett test, hence the scree test, and tests for a common factor model and for the significance of a correlation matrix are explicated. PMID- 26821850 TI - Micro/nanostructured surface modification using femtosecond laser pulses on minimally invasive electrosurgical devices. AB - The purpose of the present study was to examine thermal damage and a sticking problem in the tissue after the use of a minimally invasive electrosurgical device with a nanostructured surface treatment that uses a femtosecond laser pulse (FLP) technique. To safely use an electrosurgical device in clinical surgery, it is important to decrease thermal damage to surrounding tissues. The surface characteristics and morphology of the FLP layer were evaluated using optical microscopy, scanning electron microscopy, and transmission electron microscopy; element analysis was performed using energy-dispersive X-ray spectroscopy, grazing incidence X-ray diffraction, and X-ray photoelectron spectroscopy. In the animal model, monopolar electrosurgical devices were used to create lesions in the legs of 30 adult rats. Animals were sacrificed for investigations at 0, 3, 7, 14, and 28 days postoperatively. Results indicated that the thermal damage and sticking situations were reduced significantly when a minimally invasive electrosurgical instrument with an FLP layer was used. Temperatures decreased while film thickness increased. Thermographic data revealed that surgical temperatures in an animal model were significantly lower in the FLP electrosurgical device compared with that in the untreated one. Furthermore, the FLP device created a relatively small area of thermal damage. As already mentioned, the biomedical nanostructured layer reduced thermal damage and promoted the antisticking property with the use of a minimally invasive electrosurgical device. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 865-873, 2017. PMID- 26821852 TI - Distortions In A Commonly Used Factor Analytic Procedure. AB - A currently popular procedure in empirical factor analytic studies is to use unities in the main diagonal as communality estimates, extract all factors with eigenvalues of 1.0 or higher, and rotate these factors by varimax. This procedure and others are applied to several previously published correlation matrices and some artificial matrices. This procedure results in the retention of too many factors, unrealistic elevation of the amount of common factor variance analyzed, and distortions in the conclusions drawn from the factor analytic investigation. Ways of avoiding these difficulties, are discussed. PMID- 26821853 TI - External Single-Set Components Analysis Of Multiple Criterion/Multiple Predictor Variables. AB - Although much progress has been made in clarifying the properties of canonical correlation analysis in order to enhance its applicability, there are several remaining problems. Canonical variates do not always represent the observed variables even though the canonical correlation is high. In addition, canonical solutions are often difficult to interpret. This paper presents a method designed to deal with these two problems. Instead of maximizing the correlation between unobserved variates, the sum of squared inter-set loadings is maximized. Contrary to the canonical correlation solution, this method ensures that the shared variance between predictor variates and criterion variables is maximal. Instead of extracting variates from both criterion and predictor variables, only one set of components (from the predictor variables) is constructed. Without loss of common variance, an orthogonal rotation is applied to the resulting loadings in order to simplify structure. PMID- 26821854 TI - Hierarchical Factoring Based On Image Analysis And Orthoblique Rotations. AB - The procedure for hierarchical factoring suggested by Schmid and Leiman (1957) is applied within the framework of image analysis and orthoblique rotational procedures. It is shown that this approach necessarily leads to correlated higher order factors. Also, one can obtain a smaller number of factors than produced by typical hierarchical procedures. PMID- 26821855 TI - A Simple Approximation For Random Rankings Stress Values. AB - Potentially more convenient than either a table or a graph of random rankings stress values is a simple analytic expression which takes as arguments N, the number of points, and D, the number of dimensions and then yields the expected stress value. Such a function is developed here, and it is shown that the error of the approximation is of the same magnitude as the standard error of the means of the original Monte Carlo data. The approximation is highly accurate for 10 < N < 60 and 1 < D < 5. The present paper represents an extension of Spence and Ogilvie (1973). PMID- 26821856 TI - Mixture Model Tests Of Hierarchical Clustering Algorithms: The Problem Of Classifying Everybody. AB - Due to the effects of outliers, mixture model tests that require all objects to be classified can severely underestimate the accuracy of hierarchical clustering algorithms. More valid and relevant comparisons between algorithms can be made by calculating accuracy at several levels in the hierarchical tree and considering accuracy as a function of the coverage of the classification. Using this procedure, several algorithms were compared on their ability to resolve ten multivariate normal mixtures. All of the algorithms were significantly more accurate than a random linkage algorithm, and accuracy was inversely related to coverage. Algorithms using correlation as the similarity measure were significantly more accurate than those using Euclidean distance (p < .001). A subset of high accuracy algorithms, including single, average, and centroid linkage using correlation, and Ward's minimum variance technique, was identified. PMID- 26821857 TI - Vaginal birth after four caesarean sections: A case report. PMID- 26821860 TI - Friedel-Crafts-Type Intermolecular C-H Silylation of Electron-Rich Arenes Initiated by Base-Metal Salts. AB - An electrophilic aromatic substitution (SE Ar) with a catalytically generated silicon electrophile is reported. Essentially any commercially available base metal salt acts as an initiator/catalyst when activated with NaBAr(F)4. The thus generated Lewis acid then promotes the SE Ar of electron-rich arenes with hydrosilanes but not halosilanes. This new C-H silylation was optimized for FeCl2/NaBAr(F)4, affording good yields at catalyst loadings as low as 0.5 mol %. The procedure is exceedingly straightforward and comes close to typical Friedel Crafts methods, where no added base is needed to absorb the released protons. PMID- 26821859 TI - Hospice care in the Netherlands: who applies and who is admitted to inpatient care? AB - BACKGROUND: Ten percent of non-sudden deaths in the Netherlands occur in inpatient hospice facilities. To investigate differences between patients who are admitted to inpatient hospice care or not following application, how diagnoses compare to the national population, characteristics of application, and associations with being admitted to inpatient hospice care or not. METHODS: Data from a database representing over 25% of inpatient hospice facilities in the Netherlands were analysed. The study period spanned the years 2007-2012. Multivariate regression analyses were performed to study associations between demographic and application characteristics, and admittance. RESULTS: Ten thousand two hundred fifty-four patients were included. 84.1% of patients applying for inpatient hospice care had cancer compared to 37.0% of deaths nationally. 52.4% of applicants resided in hospital at the time of admission. Most frequent reasons for application were the wish to die in an inpatient hospice facility (70.5%), needing intensive care or support (52.2 ), relieving caregivers (41.4%) and needing pain/symptom control (39.9%). Living alone (OR 1.68, 95% CI 1.46-1.94), having cancer (OR 1.40, 95% CI 1.11-1.76), relieving caregivers (OR 1.18, 95% CI 1.01-1.38), needing pain/symptom control (OR1.72, 95% CI 1.46-2.03) wanting inpatient hospice care until death (vs respite care) (OR 3.59, 95% CI 2.11-6.10), wanting to be admitted as soon as possible (OR 1.64, 95% CI 1.42-1.88), and being referred by a primary care professional (OR 1.36, 95% CI 1.17-1.59) were positively associated with being admitted. Wishing to die in an inpatient hospice facility was negatively associated with being admitted (OR 0.85, 95% CI 0.72-1.00). CONCLUSIONS: This study suggests that when applying for inpatient hospice care, patients who seem most urgently in need of inpatient hospice care are more frequently admitted. However, non-cancer patients seem to be an under-represented population. Staff should consider application based on need for palliation, irrespective of diagnosis. PMID- 26821858 TI - The Ccr4-Not complex is a key regulator of eukaryotic gene expression. AB - The Ccr4-Not complex is a multisubunit complex present in all eukaryotes that contributes to regulate gene expression at all steps, from production of messenger RNAs (mRNAs) in the nucleus to their degradation in the cytoplasm. In the nucleus it influences the post-translational modifications of the chromatin template that has to be remodeled for transcription, it is present at sites of transcription and associates with transcription factors as well as with the elongating polymerase, it interacts with the factors that prepare the new transcript for export to the cytoplasm and finally is important for nuclear quality control and influences mRNA export. In the cytoplasm it is present in polysomes where mRNAs are translated and in RNA granules where mRNAs will be redirected upon inhibition of translation. It influences mRNA translatability, and is needed during translation, on one hand for co-translational protein interactions and on the other hand to preserve translation that stalls. It is one of the relevant players during co-translational quality control. It also interacts with factors that will repress translation or induce mRNA decapping when recruited to the translating template. Finally, Ccr4-Not carries deadenylating enzymes and is a key player in mRNA decay, generic mRNA decay that follows normal translation termination, co-translational mRNA decay of transcripts on which the ribosomes stall durably or which carry a non-sense mutation and finally mRNA decay that is induced by external signaling for a change in genetic programming. Ccr4-Not is a master regulator of eukaryotic gene expression. WIREs RNA 2016, 7:438-454. doi: 10.1002/wrna.1332 For further resources related to this article, please visit the WIREs website. PMID- 26821862 TI - Novel Surface Passivation Technique for Low-Temperature Solution-Processed Perovskite PV Cells. AB - Low-temperature solution-processed perovskite solar cells are attracting immense interest due to their ease of fabrication and potential for mass production on flexible substrates. However, the unfavorable surface properties of planar substrates often lead to large variations in perovskite crystal size and weak charge extractions at interfaces, resulting in inferior performance. Here, we report the improved performance, reproducibility, and high stability of "p-i-n" planar heterojunction perovskite solar cells. The key fabrication process is the addition of the amine-polymer poly[(9,9-bis(3'-(N,N-dimethylamino)propyl)-2,7 fluorene)-alt-2,7-(9,9-dioctylfluorene)] (PFN-P1) to a simple spin-coating process. The PFN-P1 works as a surfactant and helps promote uniform crystallization. As a result, perovskite films with PFN-P1 have a uniform distribution of grain sizes and improved open circuit voltage. Devices with PFN P1 showed the best efficiency (13.2%), with a small standard deviation (0.40), out of 60 cells. Moreover, ~90% of the initial efficiency was retained over more than 6 months. Additionally, devices fabricated from PFN-P1 mixed perovskite films showed higher stability under continuous operation at maximum power point over 150 h. Our results show that this approach is simple and effective for improving device performance, reproducibility, and stability by modifying perovskite properties with PFN-P1. Because of the simplicity of the fabrication process and reliable performance increase, this approach marks important progress in low-temperature solution-processed perovskite solar cells. PMID- 26821868 TI - Evaluating the MESSAGE Communication Strategies in Dementia training for use with community-based aged care staff working with people with dementia: a controlled pretest-post-test study. AB - AIMS AND OBJECTIVES: The study aims to evaluate the effects of a communication skills training programme on community aged care staff's knowledge of communication support in dementia and on staff's care experience. BACKGROUND: Dementia can lead to impairments in communication. Therefore, quality community based dementia care requires that staff be skilled communicators, equipped to facilitate interactions with people with dementia. The current investigation evaluated the effectiveness of the MESSAGE Communication Strategies in Dementia for Care Staff training programme with respect to knowledge of communication support and the staff/caregiver experience. DESIGN: A multi-centre controlled pretest/post-test design with randomised cohort allocation was used. Outcome measures were completed at baseline, immediately after training (training group only), and at three-month follow-up. METHODS: Thirty-eight care staff working in community aged care participated and completed all outcome measures (training = 22; control = 16).Training and control groups completed the following outcome measures: knowledge of communication support strategies, self-efficacy, preparedness to provide care, strain in nursing care and attitude to dementia care. Staff in the training group provided written feedback on the training. RESULTS: A significant improvement in knowledge scores from baseline was found for the training group both immediately after training and at three-month follow up. There was also a significant training effect for self-efficacy and preparedness to provide care. No significant difference was found for the control group for any measure. No significant training effects were found for measures of strain or attitudes to dementia care. Feedback from staff suggests that the training was well received. CONCLUSIONS: The MESSAGE training was positively received by staff and had a significant effect on care staff knowledge, and confidence to provide care for people with dementia. RELEVANCE TO CLINICAL PRACTICE: The easily accessible multimedia training programme is well received by staff and has the potential to improve quality of care. PMID- 26821869 TI - Triploid human embryonic stem cells derived from tripronuclear zygotes displayed pluripotency and trophoblast differentiation ability similar to the diploid human embryonic stem cells. AB - Because the diploid human embryonic stem cells (hESCs) can be successfully derived from tripronuclear zygotes thus, they can serve as an alternative source of derivation of normal karyotype hESC lines. The aim of the present study was to compare the pluripotency and trophoblast differentiation ability of hESCs derived from tripronuclear zygotes and diploid hESCs. In the present study, a total of 20 tripronuclear zygotes were cultured; 8 zygotes developed to the blastocyst stage and 1 hESC line was generated. Unlike the previous studies, chromosomal correction of tripronuclear zygotes during derivation of hESCs did not occur. The established line carries 3 sets of chromosomes and showed a numerical aberration. Although the cell line displayed an abnormal chromosome number, it was found the cell line has been shown to be pluripotent with the ability to differentiate into 3 embryonic germ layers both in vitro and in vivo. The expression of X inactive specific transcript (XIST) in mid-passage (passage 42) of undifferentiated triploid hESCs was detected, indicating X chromosome inactivation of the cell line. Moreover, when this cell line was induced to differentiate toward the trophoblast lineage, morphological and functional trophoblast cells were observed, similar to the diploid hESC line. PMID- 26821871 TI - All-solution processed semi-transparent perovskite solar cells with silver nanowires electrode. AB - In this work, we report an all-solution route to produce semi-transparent high efficiency perovskite solar cells (PSCs). Instead of an energy-consuming vacuum process with metal deposition, the top electrode is simply deposited by spray coating silver nanowires (AgNWs) under room temperature using fabrication conditions and solvents that do not damage or dissolve the underlying PSC. The as fabricated semi-transparent perovskite solar cell shows a photovoltaic output with dual side illuminations due to the transparency of the AgNWs. With a back cover electrode, the open circuit voltage increases significantly from 1.01 to 1.16 V, yielding high power conversion efficiency from 7.98 to 10.64%. PMID- 26821872 TI - Phenyltrimethylammonium Salts as Methylation Reagents in the Nickel-Catalyzed Methylation of C-H Bonds. AB - Methylation of C(sp(2))-H bonds was achieved through the Ni(II)-catalyzed reaction of benzamides with phenyltrimethylammonium bromide or iodide as the source of the methyl group. The reaction has a broad scope and shows high functional-group compatibility. The reaction is also applicable to the methylation of C(sp(3))-H bonds in aliphatic amides. PMID- 26821863 TI - Synthetic Biomaterials from Metabolically Derived Synthons. AB - The utility of metabolic synthons as the building blocks for new biomaterials is based on the early application and success of hydroxy acid based polyesters as degradable sutures and controlled drug delivery matrices. The sheer number of potential monomers derived from the metabolome (e.g., lactic acid, dihydroxyacetone, glycerol, fumarate) gives rise to almost limitless biomaterial structural possibilities, functionality, and performance characteristics, as well as opportunities for the synthesis of new polymers. This review describes recent advances in new chemistries, as well as the inventive use of traditional chemistries, toward the design and synthesis of new polymers. Specific polymeric biomaterials can be prepared for use in varied medical applications (e.g., drug delivery, tissue engineering, wound repair, etc.) through judicious selection of the monomer and backbone linkage. PMID- 26821870 TI - Ultrastructural comparison of porcine putative embryonic stem cells derived by in vitro fertilization and somatic cell nuclear transfer. AB - The ultrastructure of porcine putative embryonic stem cells and porcine fetal fibroblasts (PFFs) was analyzed by transmission electron microscopy. The aim of this study was to compare the features of organelles in in vitro fertilization (IVF) derived porcine embryonic stem cells (IVF-pESCs) and somatic cell nuclear transfer (SCNT) derived pESCs (SCNT-pESCs). Also, the features of organelles in high-passage IVF-pESCs were compared with those in low-passage cells. The ultrastructure of PFFs showed rare microvilli on the cell surfaces, polygonal or irregular nuclei with one to two reticular-shaped nucleoli and euchromatin, low cytoplasm-to-nucleus ratios, rare ribosomes, rare rough endoplasmic reticulum, elongated mitochondria, rich lysosomes and rich phagocytic vacuoles. IVF-pESCs showed rare microvilli on the cell surfaces, round or irregular nuclei with one to two reticular-shaped nucleoli and euchromatin, low cytoplasm-to-nucleus ratios, rich ribosomes, long stacks of rough endoplasmic reticulum, elongated mitochondria, rare lysosomes and rare autophagic vacuoles. By contrast, SCNT pESCs showed rich microvilli with various lengths and frequencies on the cell surfaces, polygonal nuclei with one reticular shaped nucleoli and heterochromatin, high cytoplasm-to-nucleus ratios, rare ribosomes, rare rough endoplasmic reticulum, round mitochondria, rich lysosomes and rich phagocytic vacuoles with clear intercellular junctions. Furthermore, high-passage IVF-pESCs showed irregularly shaped colonies, pyknosis and numerous lysosomes associated with autophagic vacuoles showing signs of apoptosis. In conclusion, this study confirms that the ultrastructural characteristics of pESCs differ depending on their origin. These ultrastructural characteristics might be useful in biomedical research using pESCs, leading to new insights regarding regenerative medicine and tissue repair. PMID- 26821873 TI - Clinical Utility of Multidetector Computed Tomography in Redo Valve Procedures. AB - BACKGROUND: Transesophageal echocardiography (TEE) is recommended for diagnosis in patients suspected of prosthetic valve dysfunction, but could be limited in its ability to identify the etiology of these dysfunctions and to assess extracardiac structures. Our objective is to examine the usefulness of multidetector computed tomography (MDCT) in establishing the etiology of the dysfunctions and its clinical utility in preoperative assessment in these patients. METHODS: Twenty-two prosthetic heart valves from 20 consecutive patients who had a preoperative MDCT and underwent redo prosthetic valve procedures from December 2008 to February 2013 were examined retrospectively. Results from MDCT and TEE were compared to intraoperative findings. Extravalvular MDCT findings including coronary artery/bypass graft, high-risk features for reoperative cardiac surgery, and extracardiac findings were also assessed. RESULTS: MDCT correctly identified 15 valve regurgitation and seven valve obstructions compared to intraoperative findings. Both TEE and MDCT were able to correctly identify the etiologies in 93% (14/15) of regurgitant valves. However, MDCT was better able to identify the etiology of obstructive valves than TEE (86% [6/7] vs. 43% [3/7]) compared to intraoperative findings. In patients who had preoperative invasive angiography, MDCT correctly identified two patients with significant coronary artery disease (CAD) and ruled out 11 without significant CAD. Furthermore, MDCT detected five high-risk features for postoperative complications and eight clinically relevant extracardiac findings. CONCLUSIONS: MDCT displayed comparable or better diagnostic performance than TEE for identifying the type of dysfunction and its etiology, as well as providing additional coronary and other extravalvular evaluations useful for preoperative planning. PMID- 26821874 TI - Directly Diphenylborane-Fused Porphyrins. AB - Mono- and bis(diphenylborane)-fused porphyrins were synthesized from the corresponding beta-(2-trimethylsilylphenyl)-substituted porphyrins through the sequence of Si-B exchange reaction, intramolecular bora-Friedel-Crafts reaction, and ring-closing Si-B exchange reaction. Effective electronic interactions of the empty p-orbital of the boron atom with the porphyrin pi-circuit lead to red shifted absorption spectra and substantially decreased LUMO energy levels. Pyridine adds at the boron center to cause disruption of the electronic interaction of the boron atom with large association constants (1.9-17*10(4) m( 1)) depending on the central metal at the porphyrin. The Zn(II) complex behaved as a hetero-dinuclear Lewis acid, exhibiting regioselective binding of pyridines at the boron or the zinc center. PMID- 26821875 TI - Tweet if you want to be sustainable: a thematic analysis of a Twitter chat to discuss sustainability in nurse education. AB - AIM: To explore the concept of sustainability in nursing using social media as a vehicle for discussion on the topic. BACKGROUND: There is a need for an increased awareness among nurses of the issues that are crucial for the healthcare sector to prepare for climate change and contribute to sustainable development. However, topics about sustainability and climate change are not a requirement of nursing curricula in Europe; social media provides an opportunity to raise issues and promote discussion. DESIGN: A thematic analysis of a Twitter discussion. METHODS: A Twitter discussion session hosted by @WeNurses took place on 24 March 2015 over 1 hour. Data were gathered via this online discussion hosted on Twitter, a social media platform. Following the discussion a thematic analysis of the posted Tweets was conducted. FINDINGS: One hundred and nineteen people posted nine hundred and ninety six Tweets, a reach of 3,306,368. Tweets broadly followed the questions posted by the team. Several threads related to the sustainable use of healthcare resources and the need to reduce waste was evident. A Word Cloud of the Tweets highlighted prominent words in the discussion: sustainability, nursing/nurses, curriculum, important, waste, practice, resources, student, plastic, health, gloves. CONCLUSION: Social media is an effective way of engaging nurses and students in a discussion on challenging issues. Sustainability appears to be important for nurses, with a particular emphasis on resource use and the importance of sustainability topics in nurse education. PMID- 26821876 TI - Adding a transversus abdominis plane block to parenteral opioid for postoperative analgesia following trans-abdominal hysterectomy in a low resource setting: a prospective, randomised, double blind, controlled study. AB - BACKGROUND: The current gold standard treatment for acute postoperative pain after major abdominal surgery is multimodal analgesia using patient controlled analgesia delivery systems. Patient controlled analgesia systems are expensive and their routine use in very low income countries is not practical. The use of ultrasound in anaesthesia has made some regional anaesthesia blocks technically easy and safe to perform. This study aimed to determine whether adding an ultrasound guided transversus abdominis plane block as an adjunct to the current parenteral opioid based regimen would result in superior pain relief after a trans abdominal hysterectomy compared to using parenteral opioids alone. METHODS: Thirty-two elective patients having trans abdominal hysterectomy were recruited into a prospective randomised double-blind, controlled study comparing a bilateral transversus abdominis plane block using 21 ml of 0.25% bupivacaine and 4.0 mg dexamethasone with a sham block containing 21 ml 0.9% saline. Sixteen patients were allocated to each group. Anaesthesia and postoperative analgesia was left to the attending anaesthetist's discretion. Primary outcome was visual analogue scale for pain at 2 h and 4 h. Secondary outcomes were time to first request for analgesia, visual analogue scale for comfort and bother. The data were analysed using the Statistical Package for Social Sciences (SPSS version 16). RESULTS: There was no statistically significant difference in the demographics of the two groups regarding weight, height, physical status and type of surgical incision. There was a statistically significant difference in visual analogue scale for pain at 4 h during movement with lower pain scales in the test group (p = 0.034). Women in the control group had an average pain free period of 56.8 min (median 56.5 min) before requesting a rescue analgesic compared to 116.5 min (median 103 min) in the study group. The between group difference in the average total analgesia duration was statistically significant at the 0.05 level (p = 0.005). CONCLUSION: The addition of a bupivacaine-dexamethasone transverse abdominis plane block to intramuscular opioid does produce superior acute post operative pain relief following a hysterectomy. However a single-shot block has a limited duration of action, and we recommend a repeat block. TRIAL REGISTRATION: Clinical trials registration was obtained PACTR201501000965252. http//www.pactr.org/ATMWeb/appmanager/atm/atmregistry?_nfpb=true&_windowLabel=Bas cSearchUpdateController_1&BasicSearchUpdateController_1_actionOverride=%2Fpageflo s%2Ftrial%2FbasicSearchUpdate%2FviewTrail&BasicSearchUpdateController_1id=965. The trial was registered on the 12th Dec 2014. PMID- 26821877 TI - Reversal of sensory deficit through sacral neuromodulation in an animal model of fecal incontinence. AB - BACKGROUND: Sacral neuromodulation (SNM) is a treatment option for intractable fecal incontinence. The mechanism of action is unclear, however, increasing evidence for afferent somatosensory effects exists. This study's aim was to elucidate effects of acute SNM on the cerebral cortex in a rodent model of pudendal nerve injury. METHODS: The effects of 14 Hz and 2 Hz SNM on sensory cortical activation were studied. In 32 anesthetized rats, anal canal evoked potentials (EPs) were recorded over the primary somatosensory cortex. Pudendal nerve injury was produced by 1-hour inflation of two intra-pelvic balloons. Four groups were studied: balloon injury, balloon injury plus either 14 Hz or 2 Hz SNM, sham operation. Immunohistochemistry for the neural plasticity marker polysialylated neural cell adhesion molecule (PSA-NCAM) positive cells (numerical density and location) in the somatosensory cortex was performed. KEY RESULTS: Anal EP amplitudes diminished during balloon inflation; 14 Hz SNM restored diminished anal EPs to initial levels and 2 Hz SNM to above initial levels. Evoked potential latencies were prolonged during balloon inflation. The numerical density of PSA-NCAM positive cells increased in the SNM groups, but not in sham or balloon injury without SNM. Stimulated cortices showed clusters of PSA-NCAM positive cells in layers II, IV, and V. Post SNM changes were similar in both SNM groups. CONCLUSIONS & INFERENCES: Sacral neuromodulation augments anal representation in the sensory cortex and restores afferent pathways following injury. PSA-NCAM positive cell density is increased in stimulated cortices and positive cells are clustered in layers II, IV, and V. PMID- 26821878 TI - The contribution of Alu exons to the human proteome. AB - BACKGROUND: Alu elements are major contributors to lineage-specific new exons in primate and human genomes. Recent studies indicate that some Alu exons have high transcript inclusion levels or tissue-specific splicing profiles, and may play important regulatory roles in modulating mRNA degradation or translational efficiency. However, the contribution of Alu exons to the human proteome remains unclear and controversial. The prevailing view is that exons derived from young repetitive elements, such as Alu elements, are restricted to regulatory functions and have not had adequate evolutionary time to be incorporated into stable, functional proteins. RESULTS: We adopt a proteotranscriptomics approach to systematically assess the contribution of Alu exons to the human proteome. Using RNA sequencing, ribosome profiling, and proteomics data from human tissues and cell lines, we provide evidence for the translational activities of Alu exons and the presence of Alu exon derived peptides in human proteins. These Alu exon peptides represent species-specific protein differences between primates and other mammals, and in certain instances between humans and closely related primates. In the case of the RNA editing enzyme ADARB1, which contains an Alu exon peptide in its catalytic domain, RNA sequencing analyses of A-to-I editing demonstrate that both the Alu exon skipping and inclusion isoforms encode active enzymes. The Alu exon derived peptide may fine tune the overall editing activity and, in limited cases, the site selectivity of ADARB1 protein products. CONCLUSIONS: Our data indicate that Alu elements have contributed to the acquisition of novel protein sequences during primate and human evolution. PMID- 26821880 TI - Three-dimensional homology model of GlcNAc-TV glycosyltransferase. AB - The enzyme UDP-N-acetylglucosamine: alpha-d-mannoside beta-1-6 N acetylglucosaminyltransferase V (GnT-V) catalyzes the transfer of GlcNAc from the UDP-GlcNAc donor to the alpha-1-6-linked mannose of the trimannosyl core structure of glycoproteins to produce the beta-1-6-linked branching of N-linked oligosaccharides. beta-1-6-GlcNAc-branched N-glycans are associated with cancer growth and metastasis. Therefore, the inhibition of GnT-V represents a key target for anti-cancer drug development. However, the development of potent and specific inhibitors of GnT-V is hampered by the lack of information on the three dimensional structure of the enzyme and on the binding characteristics of its substrates. Here we present the first 3D structure of GnT-V as a result of homology modeling. Various alignment methods, docking the donor and acceptor substrates, and molecular dynamics simulation were used to construct seven homology models of GnT-V and characterize the binding of its substrates. The best homology model is consistent with available experimental data. The three dimensional model, the structure of the enzyme catalytic site and binding information obtained for the donor and acceptor can be useful in studies of the catalytic mechanism and design of inhibitors of GnT-V. PMID- 26821879 TI - Atopic dermatitis is not associated with actinic keratosis: cross-sectional results from the Rotterdam study. AB - BACKGROUND: Epidermal barrier impairment and an altered immune system in atopic dermatitis (AD) may predispose to ultraviolet-induced DNA damage. OBJECTIVES: To study the association between AD and actinic keratosis (AK) in a population-based cross-sectional study. METHODS: AD was defined by modified criteria of the U.K. working party's diagnostic criteria. AKs were diagnosed by physicians during a full-body skin examination, and keratinocyte cancers were identified via linkage to the national pathology database. The results were analysed in adjusted multivariable and multinomial models. RESULTS: A lower proportion of subjects with AD had AKs than those without AD: 16% vs. 24%, P = 0.002; unadjusted odds ratio (OR) 0.60, 95% confidence interval (CI) 0.42-0.83; adjusted OR 0.74, 95% CI 0.51-1.05; fully adjusted OR 0.69, 95% CI 0.47-1.07. In a multinomial model patients with AD were less likely to have >= 10 AKs (adjusted OR 0.28, 95% CI 0.09-0.90). No effect of AD on basal cell carcinoma or squamous cell carcinoma was found: adjusted OR 0.71, 95% CI 0.41-1.24 and adjusted OR 1.54, 95% CI 0.66 3.62, respectively. CONCLUSIONS: AD in community-dwelling patients is not associated with AK. PMID- 26821881 TI - Novel and sensitive UPLC-MS/MS method for quantification of sofosbuvir in human plasma: application to a bioequivalence study. AB - A novel and sensitive LC-MS/MS method was developed and validated for determination of sofosbuvir (SF) using eplerenone as an internal standard. The Xevo TQD LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. Extraction with tert-butyl methyl ether was used in sample preparation. The prepared samples were chromatographed on Acquity UPLC BEH C18 (50 * 2.1 mm, 1.7 MUm) column by pumping 0.1% formic acid and acetonitrile in an isocratic mode at a flow rate of 0.35 mL/min. Method validation was performed as per the US Food and Drug Administration guidelines and the standard curves were found to be linear in the range of 0.25-3500 ng/mL for SF. The intra- and inter-day precision and accuracy results were within the acceptable limits. A very short run time of 1 min made it possible to analyze more than 500 human plasma samples per day. A very low quantification limit of SF allowed the applicability of the developed method for determination of SF in a bioequivalence study in human volunteers. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26821882 TI - Polyphyllin I induces cell cycle arrest and apoptosis in human myeloma cells via modulating beta-catenin signaling pathway. AB - Multiple myeloma (MM) is an indolent B-cell disease characterized by clonal proliferation of malignant plasma cells. Multiple myeloma remains incurable despite new targeted drugs and development of drug resistance or intolerable toxicity emerges as a major problem. Therefore, design, identification, and validation of novel chemicals with therapeutic potential are clearly needed for MM treatment. Here, we explore polyphyllin I (PPI), a major active constituent extracted from Paris polyphyllin, its inhibitory effects and its mechanisms in MM cells in vitro. We found that PPI inhibited the proliferation of myeloma cells. The combination of PPI with dexamethasone, doxorubicin, arsenic trioxide, or bortezomib enhanced the inhibition of cell growth. As analyzed by flow cytometry, MM cells were arrested at G2/M phase and apoptotic cells increased in a time dependent manner. Morphological changes of cells undergoing apoptosis were observed under light microscope. To explore the mechanism of apoptosis induced by PPI, we next examined whether the Wingless-Int (Wnt)/beta-catenin signaling pathway played a role in the PPI-induced growth inhibition in MM cells. The canonical Wnt signaling pathway is activated in MM cells through constitutively active beta-catenin, a messenger molecule relevant to growth, survival, and migration of MM cells. Western blotting was used to measure the protein levels of beta-catenin, and PPI treatment led to downregulating the expression of beta catenin protein and was followed by inhibition of beta-catenin nuclear localization. As a result, beta-catenin downstream targets, such as cyclin D1 and survivin, were downregulated. To the best of our knowledge, this is the first report identifying anti-proliferative potency of PPI against myeloma cells. PPI blocks beta-catenin nuclear translocation and decreasing expression of the downstream targets of beta-catenin. Our results suggest that PPI is a novel inhibitor of beta-catenin activity with potential anti-myeloma efficacy. PMID- 26821883 TI - Growth behavior of gold nanoparticles synthesized in unsaturated fatty acids by vacuum evaporation methods. AB - Physical vapor evaporation of metals on low vapor pressure liquids is a simple and clean method to synthesize nanoparticles and thin films, though only little work has been conducted so far. Here, gold nanoparticles were synthesized by vacuum evaporation (VE) methods in ricinoleic acid and oleic acid, two typical unsaturated fatty acids (UFAs). The two solvents formed black aggregates after deposition and then shrunk and finally disappeared with the progress of time. By transmission electron microscopy (TEM) images, nanoparticles in ricinoleic acids formed aggregates and then dispersed by time, while in oleic acid big aggregates were not observed in all timescales. From TEM images and small angle X-ray scattering (SAXS) measurements, the mean size of the nanoparticles was about 4 nm in both ricinoleic and oleic acids. UV-Vis spectra were also taken as a function of time and the results were consistent with the growth behavior presumed by TEM images. Air exposure had an influence on the behavior of the sample triggering the nanoparticle formation in both solvents. From control experiments, we discovered that oxygen gas triggered the phenomenon and nanoparticles function as a catalyst for the oxidation of the UFAs. It stimulates the phenomenon and in ricinoleic acid, specifically, electrons are transferred from riconleic acid to the gold nanoparticles, enhancing the surface potential of the nanoparticles and the repulsive force between their electronic double layers. PMID- 26821885 TI - Copper(i) chloride promoted Csp(2)-N cross-coupling of 1,2-di(pyrimidin-2-yl) disulfides with amines: an efficient approach to obtain C2-amino functionalized pyrimidines. AB - The copper(i)-promoted cross-coupling of 1,2-di(pyrimidin-2-yl) disulfides with aromatic amines and aliphatic amines to deliver C-N coupling products in moderate to good yields is reported in this paper. Central to this strategy is the conversion of disulfides into aryl- and alkyl amines by a copper-promoted chemoselective C-S bond cleavage. PMID- 26821884 TI - Analysis of Wellbore Skin Samples-Typology, Composition, and Hydraulic Properties. AB - The presence of a wellbore skin layer, formed during the drilling process, is a major impediment for the energy-efficient use of water wells. Many models exist that predict its potential impacts on well hydraulics, but so far its relevant hydraulic parameters were only estimates or, at best, model results. Here, we present data on the typology, thickness, composition, and hydraulic properties obtained from the sampling of excavated dewatering wells in lignite surface mines and from inclined core drilling into the annulus of an abandoned water well. Despite the limited number of samples, several types of skin were identified. Both surface cake filtration and particle straining in the aquifer occur. The presence of microcracks may be a determining feature for the hydraulic conductivity of skin layers. In the case of the well-developed water supply well, no skin layer was detected. The observed types and properties of wellbore skin samples can be used to test the many mathematical skin models. PMID- 26821887 TI - Legal Battles Over Embryos After In Vitro Fertilization: Is There a Way to Avoid Them? PMID- 26821889 TI - Surgery and anaesthesia in the South African context: Looking forward. AB - The National Forum on Global Surgery and Anaesthesia presents the first step towards the objective acknowledgement of the challenges of providing safe, accessible, effective and affordable surgical and anaesthetic care in the South African context. Incorporating the input of local and international, surgical, anaesthetic and public health, academic and non-academic, and private and public stakeholders, the foundation to systematically discuss and tackle issues of infrastructure, workforce, service delivery, financing and information management challenges has been formed. It is now incumbent on us as the medical community to continue this momentum and effect real change. PMID- 26821888 TI - Collaboration is key to strengthening surgical research capacity in sub-Saharan Africa. AB - The paucity of research in areas of greatest clinical need must be addressed urgently. We propose a model of collaboration in an era of information systems and emerging mobile health technology that has had significant success across the UK and has shown early encouraging results in South Africa (SA). We foresee that recent examples of surgical research collaboratives in SA will continue to promote regional, national and international 'hub-and-spoke' models and ultimately increase the South-South collaboration that is urgently needed to diffuse the skills and knowledge required to address the unmet surgical need in sub-Saharan Africa. PMID- 26821890 TI - Data mining and biological sample exportation from South Africa: A new wave of bioexploitation under the guise of clinical care? AB - Discovery Health, one of the leading healthcare funders in South Africa (SA), will offer genetic testing to its members for USD250 (approximately ZAR3 400) per test from 2016. On the surface, this appears to be innovative and futuristic. However, a deeper look at this announcement reveals considerable problems in the exportation of biological samples and data out of SA, and brings into sharp focus the lack of protection in place for potential donors. In return for a reduced cost genetic test, which will nevertheless be billed to a member's savings plan, data from the patient's results, and probably the sample itself, will be sent to the USA for storage, research purposes and possible commercial use, with no further benefit for the patient. This development has demonstrated the need for more stringent protection of the movement of biological samples and data out of SA, particularly with reference to consenting procedures, material transfer agreements, and the export of biological data themselves. PMID- 26821891 TI - Implications of direct-to-consumer whole-exome sequencing in South Africa. AB - This editorial examines a number of vitally important ethical, legal and scientific concerns that have to be addressed to ensure proper and ethical implementation of direct-to-consumer whole-exome sequencing in South Africa. Individuals taking part in this endeavour must be fully informed of the positive and negative sequelae. PMID- 26821892 TI - Challenging the cost of clinical negligence. AB - Healthcare professionals in South Africa (SA) are facing challenging times. As the clinical negligence claims environment in SA deteriorates, the impact is being felt by healthcare professionals, but also by the wider public owing to the strain that costs place on the public purse. The authors look at the current claims environment, and explain why a debate about reform is so important. PMID- 26821893 TI - An effective approach to chronic kidney disease in South Africa. AB - Very few patients with end-stage kidney disease in South Africa receive renal replacement treatment (RRT), despite the rapidly growing demand, because of resource constraints. Nephrologists who agonise daily about who to treat and who not to, and have been doing so since the inception of dialysis in this country, welcomed the opportunity to interact with the National Department of Health at a recent summit of stakeholders. The major challenges were identified and recommendations for short- to long-term solutions were made. While the renal community can still improve efficiencies, it is clear that much of the responsibility for improving access to RRT and reducing inequities must be borne by the national government. The summit marks the first step in a process that we hope will ultimately culminate in universal access to RRT for all South Africans. PMID- 26821894 TI - The decolonialisation of medicine in South Africa: Threat or opportunity? AB - The South African Traditional Health Practitioners Act 22 of 2007 is now fait accompli. The Act has been promulgated and the Department of Health (DoH) is proceeding with its implementation. An Interim Traditional Health Practitioners Council and a dedicated DoH deputy director have been appointed, the appointment of a registrar is being finalised, and the DoH has conducted a roadshow to introduce the Act and its implications to groups of traditional health practitioners (THPs) countrywide. The objective is eventual formalisation and professionalisation of THP practice to provide appropriate primary healthcare services through co-operation with biomedical service providers. Biomedical practitioners should understand the provisions of Act 22, and how this may affect their own practices. PMID- 26821895 TI - A multicentre evaluation of emergency abdominal surgery in South Africa: Results from the GlobalSurg-1 South Africa study. AB - BACKGROUND: GlobalSurg-1 was a multicentre, international, prospective cohort study conducted to address the global lack of surgical outcomes data. Six South African (SA) hospitals participated in the landmark surgical outcomes study. In this subsequent study, we collated the data from these six local participants and hypothesised that the location of surgery was an independent risk factor for an adverse outcome following emergency intraperitoneal surgery. METHODS: Participating hospitals contributed 30-day outcomes data of consecutive emergency intraperitoneal surgical operations performed during a 2-week period between July and November 2014. The six heterogeneous hospital cohorts were compared by categorical confounders. The primary outcome measure was in-hospital mortality; secondary outcome measures were in-hospital morbidity and length of stay of >14 days. The unadjusted association between hospital and adverse outcome and the univariate association between categorical confounders and adverse outcome were tested. Significant associations were further tested by a multivariate stepwise forward logistic regression model built for each outcome of interest. RESULTS: Six hospitals (designated 1 - 6) contributed outcomes data for 169 operations. The mean age of the patients was 34.9 years (range 9 - 82), 116 (68.6%) were male, and the majority (37.2%) presented as a result of trauma. Hospital 5 was associated with 76-fold increased odds of in-hospital death and 58-fold increased odds of a major in-hospital complication, and hospital 3 was associated with 3 fold increased odds of any in-hospital complication. The final model predicting in-hospital death had a receiver operating characteristic curve statistic of 0.8892. CONCLUSION: The hospital is an independent risk factor for risk-adjusted adverse outcomes following emergency intraperitoneal surgery in SA. PMID- 26821896 TI - South African surgical registrar perceptions of the research project component of training: Hope for the future? AB - BACKGROUND: The Health Professions Council of South Africa requires that a research project be submitted and passed before registration as a specialist. OBJECTIVE: To describe surgical registrars' perceptions of the compulsory research project. METHOD: Ethics clearance was received before commencing the study. A questionnaire was developed to collect feedback from surgical registrars throughout South Africa (SA). Completed questionnaires underwent descriptive analysis using MS Excel. Fisher's exact test and the chi2 test were used to compare perceptions of the research-experienced and research-naive groups. RESULTS: All medical schools in SA were sampled, and 51.5% (124/241) of surgical registrars completed the questionnaire. Challenges facing registrars included insufficient time (109/124), inadequate training in the research process (40/124), inadequate supervision (31/124), inadequate financial resources (25/124) and lack of research continuity (11/124). Of the registrars sampled, 67.7% (84/124) believed research to be a valuable component of training. An overwhelming percentage (93.5%, 116/124) proposed a dedicated research block of time as a potential solution to overcoming the challenges encountered. Further proposals included attending a course in research methodology (79/124), supervision by a faculty member with an MMed or higher postgraduate degree (73/124), and greater research exposure as an undergraduate (56/124). No statistically significant differences were found between the perceptions of the research-experienced and research-naive groups. CONCLUSION: Challenges facing surgical registrars in their efforts to complete their research projects were identified and solutions to these problems proposed. It is heartening that respondents have suggested solutions to the problems they encounter, and view research as an important component of their careers. PMID- 26821897 TI - Favourable outcomes for the first 10 years of kidney and pancreas transplantation at Wits Donald Gordon Medical Centre, Johannesburg, South Africa. AB - BACKGROUND: It is important for centres participating in transplantation in South Africa (SA) to audit their outcomes. Wits Donald Gordon Medical Centre (WDGMC), Johannesburg, SA, opened a transplant unit in 2004. The first 10 years of kidney and pancreas transplantation were reviewed to determine outcomes in respect of recipient and graft survival. METHODS: A retrospective review was conducted of all kidney-alone and simultaneous kidney-pancreas (SKP) transplants performed at WDGMC from 1 January 2004 to 31 December 2013, with follow-up to 31 December 2014 to ensure at least 1 year of survival data. Information was accessed using the transplant registers and clinical records in the transplant clinic at WDGMC. The Kaplan-Meier method was used to estimate 1-, 5- and 10-year recipient and graft survival rates for primary (first graft) kidney-alone and SKP transplants. RESULTS: The overall 10-year recipient and graft survival rates were 80.4% and 66.8%, respectively, for kidney-alone transplantation. In the kidney-alone group, children tended towards better recipient and graft survival compared with adults, but this was not statistically significant. In adults, recipient survival was significantly better for living than deceased donor type. Recipient and graft survival were significantly lower in black Africans than in the white (largest proportion in the sample) reference group. For SKP transplants, the 10-year recipient survival rate was 84.7%, while kidney and pancreas graft survival rates were 73.1% and 43.2%, respectively. CONCLUSION: Outcomes of the first 10 years of kidney and pancreas transplantation at WDGMC compare favourably with local and international survival data. PMID- 26821898 TI - Factors determining clinical outcomes in intussusception in the developing world: Experience from Johannesburg, South Africa. AB - BACKGROUND: Rates of open reduction of intussusception were noted to be unacceptably high during an institutional internal audit. OBJECTIVES: To determine the impact of revised protocols to better select patients for pneumatic reduction (PR), and document associated morbidity and mortality, and the factors that affect the above. METHODS: Medical records of patients between 3 months and 3 years of age presenting to the Department of Paediatric Surgery at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, from 2007 to 2010 were reviewed. Determining factors, including duration of symptoms, admission C reactive protein (CRP) level and weight, were analysed against clinical outcomes, notably PR, bowel resection, relook laparotomy and death. RESULTS: A total of 97 cases were suitable for inclusion. In 62 of these (63.9%), PR was attempted; this was successful in 32 cases (51.6%), giving an overall successful PR rate of 33.0%. In 7 of the 62 patients, a pneumoperitoneum was documented during the reduction attempt. Of the 65 patients who underwent surgery, 53 required intestinal resection and 12 had spontaneous or manual reduction. Ileostomy was necessary in 9 patients, and 7 required relook laparotomy. The overall mortality rate was 9.1%. Averages of 'determining factors' assessed against clinical outcome were as follows: mean weight (standard deviation (SD)) 7.4 (4.3) kg, mean duration of symptoms (DOS) 3.0 (SD 2.2) days, and admission CRP level 50.9 mg/L (range 1 - 249.3). Prolonged DOS and a raised CRP level predicted a poor outcome. CONCLUSION: Despite marked improvements in management and PR outcomes, intussusception remains associated with significant morbidity and mortality. Prolonged DOS and an elevated CRP predict worse outcomes. The use of these markers in association with clinical factors may assist management decisions, specifically with regard to operative or non-operative management. Awareness and education are key to prompt presentation and early diagnosis. Well-defined protocols introduced at all points of contact ensure early recognition and resuscitation as well as prompt referral for definitive management. PMID- 26821899 TI - Are central hospitals ready for National Health Insurance? ICD coding quality from an electronic patient discharge record for clinicians. AB - BACKGROUND: South Africa (SA)'s planned National Health Insurance reforms require the use of International Statistical Classification of Diseases (ICD) codes for hospitals to purchase services from the proposed National Health Authority. However, compliance with coding at public hospitals in the Western Cape Province has been challenging. A computer application was developed to aid clinicians in integrating ICD coding into the patient hospital discharge process. OBJECTIVE: To evaluate the quality of ICD codes captured using the application and predictors thereof in a single hospital department. METHODS: After 6 months, the quality of ICD codes was determined by comparing ICD code descriptors with medical concepts in a random sample of original patient records selected over a 6-week period. Patient and personnel characteristics influencing quality of coding, derived from a theoretical framework, were collected. RESULTS: Of 223 patient records, 45.3% (95% confidence interval (CI) 38.8 - 51.9) had complete ICD codes. Primary ICD code accuracy was 74.0% (95% CI 67.8 - 79.5). Patient characteristics such as female gender, younger age group and fewer comorbidities, as well as seniority of clinician rank, were significantly associated with ICD coding being complete on adjusted analysis. CONCLUSION: The results of this study describe ICD coding quality at a central hospital in SA supported by a computer application and the factors influencing this. More interventions are required to achieve reliable coding data, such as additional ICD coding validation tools, training and oversight of junior clinicians. PMID- 26821900 TI - Burn surgeons in South Africa: A rare species. AB - BACKGROUND: The high burden of burn injuries in South Africa (SA) requires surgeons skilled in burn care. However, there are few dedicated burn surgeons and properly equipped units or centres. OBJECTIVES: To quantify the involvement of surgeons in burn care in SA hospitals, identify factors that attract surgeons to pursue burn care as a career and deter them from doing so, and understand the challenges of hospitals treating burn patients around the country. METHODS: This was a prospective, qualitative study. Questionnaires were handed out at the South African Burn Society Congress in September 2013 and a trade symposium in March 2014. RESULTS: One hundred questionnaires were handed out, and there was a 70% response rate. Twenty-six (39%) of the respondents had a specialist surgical qualification. Only half the units had registrars (48%) and interns (51%) on their staff. Only 30% of the respondents were dedicated to burn care alone, the majority being involved on a part-time basis. The most common factor respondents suggested was needed to recruit future burn care providers, cited by 76%, was better facilities and resources. Other factors included training and skills development (59%), subspecialist training (55%), development of a diploma in burn care (52%), development of research (52%) and healthcare worker psychological support (45%). DISCUSSION: We have demonstrated that current workforce resources for burn care are inadequate, the major deficit being lack of training and the resource-restricted environment. This survey provides basic information towards workforce planning, which can be used to inform the necessary strategic decisions. PMID- 26821901 TI - Mortality in paediatric burns victims: A retrospective review from 2009 to 2012 in a single centre. AB - BACKGROUND: Childhood mortality is high in low- and middle-income countries. Burns are one of the five leading causes of childhood injury mortality in South Africa (SA). While there is an abundance of literature on burns in the developed world, there are far fewer publications dealing with childhood mortality related to burns in Africa and SA. OBJECTIVE: To describe the mortality of children admitted to a dedicated paediatric burns unit, and investigate factors contributing to reducing mortality. METHODS: A retrospective review was performed of patients admitted to the Johnson and Johnson Paediatric Burns Unit, Chris Hani Baragwanath Academic Hospital, Johannesburg, SA, between May 2009 and April 2012. RESULTS: During the study period, 1 372 patients aged <=10 years were admitted to the unit. There were 1 089 admissions to the general ward and 283 admissions to the paediatric burns intensive care unit (PBICU). The overall mortality rate was 7.9% and the rate for children admitted to the PBICU 29.3%; 90.8% of deaths occurred in children aged <=5 years. Of children admitted with an inhalational injury, 89.5% died. No child with a burn injury >60% of total body surface area (TBSA) survived. CONCLUSIONS: Our overall mortality rate was 7.9%, and the rate declined significantly over the 3-year study period from 11.7% to 5.1%. Age <=5 years, the presence of inhalational injury, burn injury >30% of TBSA and admission to the PBICU were significant risk factors for mortality. PMID- 26821902 TI - Validating homicide rates in the Western Cape Province, South Africa: Findings from the 2009 Injury Mortality Survey. AB - BACKGROUND: The Western Cape Province had the highest homicide rates in South Africa during the early 2000s. South African Police Service (SAPS) data suggested a significant decline in homicide rates in the Western Cape since 2007. It ranked second highest to the Eastern Cape Province until 2013 and ranked highest again at 52.1/100 000 in 2015. A recent national injury mortality survey offers an alternative data source to assess whether the decline in homicide rates in the Western Cape was real. METHODS: A retrospective record review of autopsies was conducted from 45 state mortuaries in eight provinces for 2009. In addition, mortality data for the Western Cape were sourced from the Provincial Injury Mortality Surveillance System. Age-standardised mortality rates and crude homicide rates per 100 000 population were calculated to compare with the SAPS crude rates. RESULTS: Our study found that the Western Cape had a provincial age standardised homicide rate of 40.1/100 000 in 2009 and ranked fourth highest among the nine provinces. The crude homicide rate of 43/100 000 for the Western Cape was similar to the SAPS provincial homicide rate of 42.4/100 000. The Northern Cape Province was the only notable exception to our provincial homicide rate ranking comparison with the SAPS for 2009. CONCLUSIONS: Conclusions. The Western Cape is fortunate to have alternative data sources to monitor trends in homicides over time. The latest release of the 2014/2015 SAPS crime statistics should be assessed in a similar manner, with a more recent data source, to validate accuracy of the provincial rates on a regular basis. PMID- 26821903 TI - Empirical antimicrobial therapy for probable v. directed therapy for possible ventilator-associated pneumonia in critically injured patients. AB - BACKGROUND: Ventilator-associated pneumonia (VAP) has recently been classified as possible or probable. Although direct attributable mortality has been difficult to prove, delay in instituting appropriate therapy has been reported to increase morbidity and mortality. Recent literature suggests that in possible VAP, instituting directed therapy while awaiting microbiological culture does not prejudice outcome compared with best-guess empirical therapy. OBJECTIVES: To ascertain outcomes of directed v. empirical therapy in possible and probable VAP, respectively. METHODS: Endotracheal aspirates were obtained from patients with suspected VAP. Those considered to have possible VAP were given directed therapy following culture results, whereas patients with more convincing evidence of VAP were classed as having probable VAP and commenced on empirical antimicrobials based on microbiological surveillance. RESULTS: Pneumonia was suspected in 106 (36.8%) of 288 patients admitted during January - December 2014. Of these, 13 did not fulfil the criteria for VAP. Of the remaining 93 (32.2%), 31 (33.3%) were considered to have probable and 62 (66.7%) possible VAP. The former were commenced on empirical antimicrobials, with 28 (90.3%) receiving appropriate therapy. Of those with possible VAP, 34 (54.8%) were given directed therapy and in 28 (45.2%) no antimicrobials were prescribed. Of the latter, 24 recovered without antimicrobials and 4 died, 3 from severe traumatic brain injury and 1 due to overwhelming intra-abdominal sepsis. No death was directly attributable to failure to treat VAP. No significant difference in mortality was found between the 34 patients with possible VAP who were commenced on directed therapy and the 31 with probable VAP who were commenced on empirical antimicrobials (p=0.75). CONCLUSIONS: Delaying antimicrobial therapy for VAP where clinical doubt exists does not adversely affect outcome. Furthermore, this policy limits the use of antimicrobials in patients with possible VAP following improvement in their clinical condition despite no therapy. PMID- 26821904 TI - An analysis of patients transported by a private helicopter emergency medical service in South Africa. AB - BACKGROUND: A helicopter emergency medical service (HEMS) is a specialist flying emergency service where on-board medical personnel have both the knowledge and equipment to perform complicated medical procedures. The paucity of literature describing the types of patients flown by HEMS in South Africa (SA) and their clinical outcome poses a challenge for current aeromedical services, as there is no baseline information on which to base flight criteria, staffing and policy documents. This has the potential to hamper the advancement of HEMS in SA. OBJECTIVES: To undertake a descriptive analysis of patients flown by the Netcare 911 HEMS over a 12-month period in Gauteng and KwaZulu-Natal (KZN) provinces, SA, and to assess patient outcomes. The clinical demographics of patients transported by the HEMS were analysed, time frames from dispatch of the helicopter to delivery of the patient to the receiving hospital determined, and patient outcomes at 24 hours and 72 hours analysed. METHODS: The study utilised a retrospective quantitative, descriptive design to analyse patients transported by a private HEMS in SA. All complete records of patients transported by the Netcare 911 HEMS between 1 January and 31 December 2011 were included. RESULTS: The final study population comprised 537 cases, as 10 cases had to be excluded owing to incomplete documentation. Of the 537 cases, 82 (15.3%) were managed by the KZN HEMS and 455 (84.7%) by the Gauteng HEMS. Adult males were the patients most commonly flown in both Gauteng and KZN (350/455 patients (76.9%) in Gauteng and 48/82 (58.5%) in KZN were males, and 364/455 patients (80.0%) in Gauteng and 73/82 (89.0%) in KZN were adults). Motor vehicle collisions were the most common incidents necessitating transport by HEMS in both operations (n=193, 35.9%). At the 24-hour follow-up, 339 patients (63.1%) were alive and stable, and at the 72 hour follow-up, 404 (75.3%) were alive and stable. CONCLUSION: The study findings provided valuable information that may have an impact on the current staffing and authorisation criteria of SA HEMS operations. PMID- 26821905 TI - Treatment and outcome of unusual animal bite injuries in young children. AB - BACKGROUND: Animal bites are a major cause of preventable traumatic injuries. OBJECTIVES: To provide more epidemiological information on animal bites, and assist in increasing awareness of the problem. METHODS: A retrospective chart review was performed including children aged >13 years presenting with bite injuries (excluding dog and human bites) to the trauma unit at Red Cross War Memorial Children's Hospital, Cape Town, South Africa, over a 25-year period. RESULTS: Two hundred and thirteen children were eligible to be entered into the study. The median age was 2.9 years (range 1.2 - 6.5), with boys slightly predominating (54.9%). Most (74.6%) of the bite injuries were inflicted by mammals, the majority (64.8) of mammalian bites being rat bites. The proportions of boys and girls in the age group 0 - 4 years bitten by rats significantly differed from the proportions in the age group >4 years (p=0.039). In the age group 0 - 4 years more girls suffered rat bites, while more boys were bitten in the age group >4 years. Of 91 rat bites, 81 (89.0%) occurred inside the house. The hands (43.9%) and the head/face/neck region (39.0%) were most affected. The underdeveloped suburbs of Philippi, Gugulethu and Khayelitsha in Cape Town represented a disproportionate number (41.6%) of rat bites. CONCLUSION: There is a relationship between poverty, unemployment, poor housing, informal settlements and rodent infestation. These high-risk populations need to be the target for government rat eradication programmes. PMID- 26821906 TI - Thrombocytopenia during pregnancy in women with HIV infection receiving no treatment. AB - Background. Thrombocytopenia (TCP) complicates 5 - 8% of pregnancies. Most cases of TCP are gestational, and the condition is usually mild and occurs in the latter part of pregnancy. Apart from pregnancy-associated medical complications such as pre-eclampsia, HIV infection is a recognised cause of TCP, and a relatively high prevalence of TCP during pregnancy would be expected in a setting with a high antenatal seroprevalence of HIV. METHODS: This was a sub-analysis of the data from a prospective trial in which the incidence of postpartum sepsis in HIV-infected women was compared with that in HIV-uninfected women. Women who were considered at low risk and eligible for vaginal delivery were recruited at 36 weeks' gestation, and followed up for 6 weeks after delivery. Full blood counts and CD4counts of HIV-infected women were obtained at baseline and repeated 6 weeks after delivery. RESULTS: The prevalence of TCP was 5.3% during pregnancy and 1.2% 6 weeks after delivery. The prevalence was similar among HIV-infected (6.0%) and HIV-uninfected women (4.7%) (p=0.292). Among the HIV-infected women, who were not receiving antiretroviral therapy (mean CD4 cell count of 453 cells/uL), there was no significant association between immunosuppression and the severity of TCP. CONCLUSIONS: Most of the TCP seen during pregnancy is of the gestational variety, and in this study HIV infection did not increase its prevalence or its severity. PMID- 26821907 TI - Which test is best for diagnosing peanut allergy in South African children with atopic dermatitis? AB - BACKGROUND: Diagnosing peanut allergy based on sensitisation alone leads to an unacceptable rate of overdiagnosis. OBJECTIVE: To define parameters that may help differentiate peanut allergy from asymptomatic sensitisation in a cohort of South African (SA) children with atopic dermatitis (AD). It is the first study in SA to utilise oral food challenge tests and analyse peanut component patterns. METHODS: This was a prospective, observational study at a paediatric university hospital in Cape Town, SA. Children with AD, aged 6 months - 10 years, were recruited randomly. They were assessed for sensitisation and allergy to peanut by questionnaire, skin-prick tests (SPTs), immuno solid-phase allergen chip (ISAC) tests, ImmunoCAP component tests to Ara h 1, 2, 3, 8 and 9, and incremental food challenges. RESULTS: One hundred participants (59 Xhosa (black Africans) and 41 of mixed race, median age 42 months) were enrolled. Overall, 44% of patients were peanut sensitised and 25% had a true peanut allergy. SPTs and ImmunoCAP Ara h 2 produced the highest areas under the receiver operating characteristic curve for predicting peanut allergy in peanut-sensitised patients. The ISAC test was less sensitive, more specific and produced significantly lower median values than ImmunoCAP tests. Ara h 2 was the most useful component in differentiating allergy from tolerance in both ethnic groups, being positive in 92% of allergic and 40% of sensitised but tolerant children (p<0.001). There was little additional contribution from Ara h 1 and 3. Ara h 8 and 9 were associated with tolerance. Commonly used 95% positive predictive values (PPVs) for SPTs, peanut-specific IgE and Ara h 2 levels fared suboptimally in our population. Maximum PPVs for this study population were found at SPT 11 mm, peanut IgE 15 kU/L and ImmunoCAP Ara h 2 of 8 kU/L, but these adjusted levels still had suboptimal PPVs in Xhosa subjects. Severe peanut allergy was associated with increased median peanut IgE and Ara h 2. CONCLUSIONS: The component Ara h 2 was useful for differentiating allergy from tolerance in both ethnic groups in this SA cohort. Ninety-five percent PPVs for peanut allergy tests may need to be revised, especially in Xhosa patients. An SPT result >=11 mm as well as Ara h 2 >=8 kU/L had the best predictive value for peanut allergy. PMID- 26821908 TI - Normal-pressure hydrocephalus presenting with psychiatric symptoms. AB - A 62-year-old man presented with a 2-month history of psychiatric symptoms. These were preceded by cognitive deterioration, urinary incontinence and an abnormal gait. A diagnosis of normal-pressure hydrocephalus (NPH) was made, and the patient improved after surgery. PMID- 26821909 TI - Boosting one-step conversion of cyclohexane to adipic acid by NO2 and VPO composite catalysts. AB - We demonstrate VPO composites as efficient catalysts for highly selective oxidation of cyclohexane to adipic acid with NO2. In particular, the Ni-Al-VPO composite catalyst exhibits the striking conversion of cyclohexane (60.6%) and exceptionally high selectivity towards adipic acid (85.0%). Moreover, N2O is an environmentally harmful gas, and its yield in the present process is only 0.03 t/t adipic acid, which is far below that obtained using the industrial method (0.3 t/t adipic acid). This work provides a new strategy for the one-step synthesis of dicarboxylic acids from cycloalkanes. PMID- 26821910 TI - A framework for scaling up health interventions: lessons from large-scale improvement initiatives in Africa. AB - BACKGROUND: Scaling up complex health interventions to large populations is not a straightforward task. Without intentional, guided efforts to scale up, it can take many years for a new evidence-based intervention to be broadly implemented. For the past decade, researchers and implementers have developed models of scale up that move beyond earlier paradigms that assumed ideas and practices would successfully spread through a combination of publication, policy, training, and example. Drawing from the previously reported frameworks for scaling up health interventions and our experience in the USA and abroad, we describe a framework for taking health interventions to full scale, and we use two large-scale improvement initiatives in Africa to illustrate the framework in action. We first identified other scale-up approaches for comparison and analysis of common constructs by searching for systematic reviews of scale-up in health care, reviewing those bibliographies, speaking with experts, and reviewing common research databases (PubMed, Google Scholar) for papers in English from peer reviewed and "gray" sources that discussed models, frameworks, or theories for scale-up from 2000 to 2014. We then analyzed the results of this external review in the context of the models and frameworks developed over the past 20 years by Associates in Process Improvement (API) and the Institute for Healthcare improvement (IHI). Finally, we reflected on two national-scale improvement initiatives that IHI had undertaken in Ghana and South Africa that were testing grounds for early iterations of the framework presented in this paper. RESULTS: The framework describes three core components: a sequence of activities that are required to get a program of work to full scale, the mechanisms that are required to facilitate the adoption of interventions, and the underlying factors and support systems required for successful scale-up. The four steps in the sequence include (1) Set-up, which prepares the ground for introduction and testing of the intervention that will be taken to full scale; (2) Develop the Scalable Unit, which is an early testing phase; (3) Test of Scale-up, which then tests the intervention in a variety of settings that are likely to represent different contexts that will be encountered at full scale; and (4) Go to Full Scale, which unfolds rapidly to enable a larger number of sites or divisions to adopt and/or replicate the intervention. CONCLUSIONS: Our framework echoes, amplifies, and systematizes the three dominant themes that occur to varying extents in a number of existing scale-up frameworks. We call out the crucial importance of defining a scalable unit of organization. If a scalable unit can be defined, and successful results achieved by implementing an intervention in this unit without major addition of resources, it is more likely that the intervention can be fully and rapidly scaled. When tying this framework to quality improvement (QI) methods, we describe a range of methodological options that can be applied to each of the four steps in the framework's sequence. PMID- 26821911 TI - Field evaluation of a PfHRP-2/pLDH rapid diagnostic test and light microscopy for diagnosis and screening of falciparum malaria during the peak seasonal transmission in an endemic area in Yemen. AB - BACKGROUND: Malaria is a public health threat in Yemen, with 149,451 cases being reported in 2013. Of these, Plasmodium falciparum represents 99%. Prompt diagnosis by light microscopy (LM) and rapid diagnostic tests (RTDs) is a key element in the national strategy of malaria control. The heterogeneous epidemiology of malaria in the country necessitates the field evaluation of the current diagnostic strategies, especially RDTs. Thus, the present study aimed to evaluate LM and an RDT, combining both P. falciparum histidine-rich protein-2 (PfHRP-2) and Plasmodium lactate dehydrogenase (pLDH), for falciparum malaria diagnosis and survey in a malaria-endemic area during the transmission season against nested polymerase chain reaction (PCR) as the reference method. METHODS: A household-based, cross-sectional malaria survey was conducted in Mawza District, a malaria-endemic area in Taiz governorate. A total of 488 participants were screened using LM and PfHRP-2/pLDH RDT. Positive samples (160) and randomly selected negative samples (52) by both RDT and LM were further analysed using 18S rRNA-based nested PCR. RESULTS: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the RDT were 96.0% (95% confidence interval (CI): 90.9-98.3), 56.0% (95% CI: 44.7-66.8), 76.3% (95% CI: 69.0-82.3), and 90.4% (95% CI: 78.8-96.8), respectively. On the other hand, LM showed sensitivity of 37.6% (95% CI: 29.6-46.3), specificity of 97.6% (95% CI: 91.7-99.7), PPV of 95.9% (95% CI: 86.3-98.9), and NPV of 51.3% (95% CI: 43.2 59.2). The sensitivity of LM dropped to 8.5% for detecting asymptomatic malaria. Malaria prevalence was 32.8% (32.1 and 37.5% for >=10 and <10 years, respectively) with the RDT compared with 10.7% (10.8 and 9.4% for age groups of >=10 and <10 years, respectively) with LM. Among asymptomatic malaria individuals, LM and RDT-based prevalence rates were 1.6 and 25.6%, respectively. However, rates of 88.2 and 94.1% of infection with P. falciparum were found among patients who reported fever in the 48 h prior to the survey by LM and PfHRP 2/pLDH RDT, respectively. CONCLUSIONS: The PfHRP-2/pLDH RDT shows high sensitivity for the survey of falciparum malaria even for asymptomatic malaria cases. Although the RDT had high sensitivity, its high false-positivity rate limits its utility as a single diagnostic tool for clinical diagnosis of malaria. On the other hand, low sensitivity of LM indicates that a high proportion of malaria cases is missed, underestimating the true prevalence of malaria in the community. Higher NPV of PfHRP-2/pLDH RDT than LM can give a straightforward exclusion of malaria among febrile patients, helping to avoid unnecessary presumptive treatments. PMID- 26821912 TI - Comparison of Target-Capture and Restriction-Site Associated DNA Sequencing for Phylogenomics: A Test in Cardinalid Tanagers (Aves, Genus: Piranga). AB - Restriction-site associated DNA sequencing (RAD-seq) and target capture of specific genomic regions, such as ultraconserved elements (UCEs), are emerging as two of the most popular methods for phylogenomics using reduced-representation genomic data sets. These two methods were designed to target different evolutionary timescales: RAD-seq was designed for population-genomic level questions and UCEs for deeper phylogenetics. The utility of both data sets to infer phylogenies across a variety of taxonomic levels has not been adequately compared within the same taxonomic system. Additionally, the effects of uninformative gene trees on species tree analyses (for target capture data) have not been explored. Here, we utilize RAD-seq and UCE data to infer a phylogeny of the bird genus Piranga The group has a range of divergence dates (0.5-6 myr), contains 11 recognized species, and lacks a resolved phylogeny. We compared two species tree methods for the RAD-seq data and six species tree methods for the UCE data. Additionally, in the UCE data, we analyzed a complete matrix as well as data sets with only highly informative loci. A complete matrix of 189 UCE loci with 10 or more parsimony informative (PI) sites, and an approximately 80% complete matrix of 1128 PI single-nucleotide polymorphisms (SNPs) (from RAD-seq) yield the same fully resolved phylogeny of Piranga We inferred non-monophyletic relationships of Piranga lutea individuals, with all other a priori species identified as monophyletic. Finally, we found that species tree analyses that included predominantly uninformative gene trees provided strong support for different topologies, with consistent phylogenetic results when limiting species tree analyses to highly informative loci or only using less informative loci with concatenation or methods meant for SNPs alone. PMID- 26821913 TI - Computational Performance and Statistical Accuracy of *BEAST and Comparisons with Other Methods. AB - Under the multispecies coalescent model of molecular evolution, gene trees have independent evolutionary histories within a shared species tree. In comparison, supermatrix concatenation methods assume that gene trees share a single common genealogical history, thereby equating gene coalescence with species divergence. The multispecies coalescent is supported by previous studies which found that its predicted distributions fit empirical data, and that concatenation is not a consistent estimator of the species tree. *BEAST, a fully Bayesian implementation of the multispecies coalescent, is popular but computationally intensive, so the increasing size of phylogenetic data sets is both a computational challenge and an opportunity for better systematics. Using simulation studies, we characterize the scaling behavior of *BEAST, and enable quantitative prediction of the impact increasing the number of loci has on both computational performance and statistical accuracy. Follow-up simulations over a wide range of parameters show that the statistical performance of *BEAST relative to concatenation improves both as branch length is reduced and as the number of loci is increased. Finally, using simulations based on estimated parameters from two phylogenomic data sets, we compare the performance of a range of species tree and concatenation methods to show that using *BEAST with tens of loci can be preferable to using concatenation with thousands of loci. Our results provide insight into the practicalities of Bayesian species tree estimation, the number of loci required to obtain a given level of accuracy and the situations in which supermatrix or summary methods will be outperformed by the fully Bayesian multispecies coalescent. PMID- 26821915 TI - Fabrication and Evaluation of Nanostructured Herbal Oil/Hydroxypropyl-beta Cyclodextrin/Polyvinylpyrrolidone Mats for Denture Stomatitis Prevention and Treatment. AB - This work aims to develop the herbal oil-incorporated nanostructure mats with antifungal activity for the prevention and treatment of Candida-associated denture stomatitis. The nanofiber mats loaded with betel oil or clove oil were fabricated via electrospinning process. The morphologies and physicochemical properties of the herbal oil loaded nanofiber mats were examined using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and mechanical testing. The release characteristic, antifungal activity, and cytotoxicity were also investigated. The SEM images confirmed the homogeneous and smooth nanoscale fibers. The addition of the herbal oil into the nanofiber mats reduced the fiber diameters. The DSC and FT-IR results confirmed the presence of the oil in the nanofiber mats. The herbal oils can be released from the mats in a very fast manner and inhibit the growth of candida cells within only few minutes after contact. These nanofiber mats may be beneficial for the prevention and treatment of denture stomatitis. PMID- 26821914 TI - Comparative transcriptional profiling of renal cortex in rats with inherited stress-induced arterial hypertension and normotensive Wistar Albino Glaxo rats. AB - BACKGROUND: The renal function plays a leading role in long-term control of arterial pressure. The comparative analysis of renal cortex transcriptome in ISIAH rats with inherited stress-induced arterial hypertension and normotensive WAG rats was performed using RNA-Seq approach. The goal of the study was to identify the differentially expressed genes (DEGs) related to hypertension and to detect the pathways contributing to the differences in renal functions in ISIAH and WAG rats. RESULTS: The analysis revealed 716 genes differentially expressed in renal cortex of ISIAH and WAG rats, 42 of them were associated with arterial hypertension and regulation of blood pressure (BP). Several Gene Ontology (GO) terms significantly enriched with DEGs suggested the existence of the hormone dependent interstrain differences in renal cortex function. Multiple DEGs were associated with regulation of blood pressure and blood circulation, with the response to stress (including oxidative stress, hypoxia, and fluid shear stress) and its regulation. Several other processes which may contribute to hypertension development in ISIAH rats were: ion transport, regulation of calcium ion transport, homeostatic process, tissue remodeling, immune system process and regulation of immune response. KEGG analysis marked out several pathways significantly enriched with DEGs related to immune system function, to steroid hormone biosynthesis, tryptophan, glutathione, nitrogen, and drug metabolism. CONCLUSIONS: The results of the study provide a basis for identification of potential biomarkers of stress-sensitive hypertension and for further investigation of the mechanisms that affect renal cortex function and hypertension development. PMID- 26821916 TI - Lanatoside C Promotes Foam Cell Formation and Atherosclerosis. AB - Lanatoside C's impact on atherosclerosis is poorly understood. The present study was conducted to determine whether lanatoside C affects the development of atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice. ApoE(-/-) mice were administered either phosphate-buffered saline (PBS) containing 0.1% DMSO (the vehicle control group) or lanatoside C at low (1 mg/kg per day) or high (2 mg/kg per day) doses, and fed a Western diet for 12 weeks. Lanatoside C dose dependently aggravated the development of atherosclerosis in the ApoE(-/-) mice compared with the vehicle control group. In an effort to determine the mechanism by which lanatoside C increased atherosclerosis, we found that lanatoside C significantly promoted the uptake of oxidised low-density lipoprotein (oxLDL) and increased foam-cell formation by upregulation of scavenger receptor class A (SR A) and the class B scavenger receptor (CD36) in macrophages. Meanwhile, the effects of lanatoside C were abolished using small interfering RNA (siRNA) inhibition of peroxisome proliferator-activated receptors beta/delta (PPARbeta/delta). Overall, our data demonstrate that lanatoside C aggravates the development of atherosclerosis by inducing PPARbeta/delta expression, which mediates upregulation of SR-A and CD36, and promotes oxLDL uptake and foam-cell formation. PMID- 26821917 TI - Impairment-targeted exercises for older adults with knee pain: a proof-of principle study (TargET-Knee-Pain). AB - BACKGROUND: Therapeutic exercise is an effective intervention for knee pain and osteoarthritis (OA) and should be individualised. In a preliminary, proof-of principle study we sought to develop a home exercise programme targeted at specific physical impairments of weak quadriceps, reduced knee flexion range of motion (ROM) and poor balance, and evaluate whether receipt of this was associated with improvements in those impairments and in patient-reported outcomes among older adults with knee pain. METHODS: This community-based study used a single group, before-after study design with 12-week follow-up. Participants were 58 adults aged over 56 years with knee pain and evidence of quadriceps weakness, loss of flexion ROM, or poor balance, recruited from an existing population-based, observational cohort. Participants received a 12-week home exercise programme, tailored to their physical impairments. The programme was led, monitored and progressed by a physiotherapist over six home visits, alternating with six telephone calls. Primary outcome measures were maximal isometric quadriceps strength, knee flexion ROM and timed single-leg standing balance, measured at baseline, 6 and 12 weeks by a research nurse blinded to the nature and content of participants' exercise programmes. Secondary outcome measures included the WOMAC. RESULTS: At 12 weeks, participants receiving strengthening exercises demonstrated a statistically significant change in quadriceps isometric strength compared to participants not receiving strengthening exercises: 3.9 KgF (95 % CI 0.1, 7.8). Changes in knee flexion ROM (2.1 degrees (-2.3, 6.5)) and single-leg balance time (-2.4 s (-4.5, 6.7)) after stretching and balance retraining exercises respectively, were not found to be statistically significant. There were significant improvements in mean WOMAC Pain and Physical Function scores: -2.2 (-3.1, -1.2) and -5.1 (-7.8, -2.5). CONCLUSIONS: A 12-week impairment-targeted, home-based exercise programme for symptomatic knee OA appeared to be associated with modest improvements in self reported pain and function but no strong evidence of greater improvement in the specific impairments targeted by each exercise package, with the possible exception of quadriceps strengthening. TRIAL REGISTRATION: Clinical Trial Registration Number: ISRCTN 61638364 Date of registration: 24 June 2010. PMID- 26821918 TI - The current practice of handling and reporting missing outcome data in eight widely used PROMs in RCT publications: a review of the current literature. AB - PURPOSE: Patient-reported outcome measures (PROMs) are designed to assess patients' perceived health states or health-related quality of life. However, PROMs are susceptible to missing data, which can affect the validity of conclusions from randomised controlled trials (RCTs). This review aims to assess current practice in the handling, analysis and reporting of missing PROMs outcome data in RCTs compared to contemporary methodology and guidance. METHODS: This structured review of the literature includes RCTs with a minimum of 50 participants per arm. Studies using the EQ-5D-3L, EORTC QLQ-C30, SF-12 and SF-36 were included if published in 2013; those using the less commonly implemented HUI, OHS, OKS and PDQ were included if published between 2009 and 2013. RESULTS: The review included 237 records (4-76 per relevant PROM). Complete case analysis and single imputation were commonly used in 33 and 15 % of publications, respectively. Multiple imputation was reported for 9 % of the PROMs reviewed. The majority of publications (93 %) failed to describe the assumed missing data mechanism, while low numbers of papers reported methods to minimise missing data (23 %), performed sensitivity analyses (22 %) or discussed the potential influence of missing data on results (16 %). CONCLUSIONS: Considerable discrepancy exists between approved methodology and current practice in handling, analysis and reporting of missing PROMs outcome data in RCTs. Greater awareness is needed for the potential biases introduced by inappropriate handling of missing data, as well as the importance of sensitivity analysis and clear reporting to enable appropriate assessments of treatment effects and conclusions from RCTs. PMID- 26821919 TI - The PROMIS FatigueFM Profile: a self-report measure of fatigue for use in fibromyalgia. AB - PURPOSE: Fibromyalgia (FM) is characterized by myriad symptoms and problems. Fatigue is one of the most common, distressing, and disabling symptoms in FM. The purpose of this study was to use fatigue item banks that were developed as part of the Patient-Reported Outcomes Measurement Information System (PROMIS) to devise a self-report measure of fatigue for use in individuals with FM. METHODS: A sample of 532 adults with FM (age range = 18-77, 96.1 % female) completed the PROMIS fatigue item bank. Factor analyses and item response theory analyses were used to identify dimensionality and optimally performing items. These data were used in combination with clinical input to select items for a fatigue self-report measure for use in FM. RESULTS: Factor analyses revealed four distinct factors in the PROMIS fatigue item bank; items for each univariate subscale were identified by selecting four items with high item information values. A 16-item measure, the PROMIS FatigueFM Profile, consisting of four 4-item short forms reflecting fatigue experience ("intensity") and fatigue impact in three subdomains-social, cognitive, and motivation-was created. The new PROMIS FatigueFM Profile short forms showed excellent internal reliability, low ceiling and floor effects, and equivalent or higher test information compared to the standard 4- and 7-item PROMIS fatigue short forms. CONCLUSIONS: The newly developed PROMIS FatigueFM Profile, a 16-item measure consisting of four 4-item short forms of self-reported fatigue severity, shows early evidence of good psychometric characteristics, provides the ability to use short forms that assess distinct aspects of fatigue experience and fatigue impact, and demonstrates equivalent or higher levels of test information compared to standard PROMIS fatigue short forms with similar number of items. The PROMIS FatigueFM Profile indicated fatigue experience and impact levels approximately 1.5 standard deviations above the normative sample mean across all short forms. Future work to evaluate the validity and reliability of this new measure in individuals with FM is needed. PMID- 26821920 TI - Thalassobius litorarius sp. nov., isolated from a tidal flat. AB - A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterium, belonging to the family Rhodobacteraceae, designated strain MME-075T, was isolated from a tidal flat. Strain MME-075T grew with 1-5% (w/v) NaCl at 20-35 degrees C and at pH 7-9. Optimal growth occurred with 2% (w/v) NaCl at 25-30 degrees C and at pH 7. The dominant respiratory quinone was ubiquinone-10, whereas summed feature 8 (C18:1omega7c and/or C18:1omega6c), 11-methyl C18:1omega7c, and C16:0 were the major fatty acids. The major polar lipids were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and an unidentified lipid. The genomic DNA G+C content was 62.1 mol%. The highest 16S rRNA gene sequence similarity values were between strain MME-075T and Thalassobius aestuarii, Thalassococcus lentus, Thalassobius maritimus and Shimia marina and were 97.6, 97.5, 97.2 and 96.2%, respectively. Neighbour-joining, maximum-likelihood and maximum-parsimony phylogenetic trees, based on 16S rRNA gene sequences, revealed that strain MME-075T clustered with species of the genus Thalassobius. Based on phenotypic and phylogenetic taxonomic properties, this strain is proposed as a representative of a novel species of the genus Thalassobius, for which the name Thalassobius litorarius sp. nov. is proposed. The type strain is MME-075T (=KCCM 43143T=JCM 30758T). PMID- 26821921 TI - A single sensor and single actuator approach to performance tailoring over a prescribed frequency band. AB - Restricted sensing and actuation control represents an important area of research that has been overlooked in most of the design methodologies. In many practical control engineering problems, it is necessitated to implement the design through a single sensor and single actuator for multivariate performance variables. In this paper, a novel approach is proposed for the solution to the single sensor and single actuator control problem where performance over any prescribed frequency band can also be tailored. The results are obtained for the broad band control design based on the formulation for discrete frequency control. It is shown that the single sensor and single actuator control problem over a frequency band can be cast into a Nevanlinna-Pick interpolation problem. An optimal controller can then be obtained via the convex optimization over LMIs. Even remarkable is that robustness issues can also be tackled in this framework. A numerical example is provided for the broad band attenuation of rotor blade vibration to illustrate the proposed design procedures. PMID- 26821922 TI - Admissibility analysis for linear singular systems with time-varying delays via neutral system approach. AB - This paper studies the admissibility problem for a class of linear singular systems with time-varying delays. In order to highlight the relations between the delay and the state, the singular system is transformed into a neutral form. Then, an appropriate type of Lyapunov-Krasovskii functionals is proposed to develop a delay-derivative-dependent admissibility condition in terms of linear matrix inequalities. The derivation combines the Wirtinger-based inequality and reciprocally convex combination method. The present criterion is also for the stability test of retarded and neutral systems with time-varying delays. Some examples are provided to illustrate the effectiveness and the benefits of the proposed method. PMID- 26821923 TI - A randomized intervention study to evaluate whether electronic messaging can increase human papillomavirus vaccine completion and knowledge among college students. AB - OBJECTIVE: To evaluate an intervention aimed at increasing human papillomavirus (HPV) vaccine completion of the 3-dose series and knowledge. PARTICIPANTS: Two hundred sixty-four male and female US college students 18-26 years old who were receiving HPV vaccine dose 1. METHODS: Students were randomly assigned to the intervention or control group. Intervention participants received the electronic intervention (text/e-mail appointment reminders and education messages) and controls received standard-of-care. Baseline/follow-up survey data were collected. Main outcome measures included vaccine completion and knowledge. RESULTS: HPV vaccine completion across groups were not significantly different for HPV dose 2 (53% vs 52%) and dose 3 (34% vs 32%). Mean knowledge score at follow-up for intervention group was significantly higher (p = .01) than at baseline. No significant differences in knowledge were found for the control group. The biggest predictor of HPV vaccine completion was female gender. CONCLUSIONS: The intervention increased knowledge but not vaccine completion. More research with catch-up age populations is needed. PMID- 26821925 TI - The sequence to hydrogenate coronene cations: A journey guided by magic numbers. AB - The understanding of hydrogen attachment to carbonaceous surfaces is essential to a wide variety of research fields and technologies such as hydrogen storage for transportation, precise localization of hydrogen in electronic devices and the formation of cosmic H2. For coronene cations as prototypical Polycyclic Aromatic Hydrocarbon (PAH) molecules, the existence of magic numbers upon hydrogenation was uncovered experimentally. Quantum chemistry calculations show that hydrogenation follows a site-specific sequence leading to the appearance of cations having 5, 11, or 17 hydrogen atoms attached, exactly the magic numbers found in the experiments. For these closed-shell cations, further hydrogenation requires appreciable structural changes associated with a high transition barrier. Controlling specific hydrogenation pathways would provide the possibility to tune the location of hydrogen attachment and the stability of the system. The sequence to hydrogenate PAHs, leading to PAHs with magic numbers of H atoms attached, provides clues to understand that carbon in space is mostly aromatic and partially aliphatic in PAHs. PAH hydrogenation is fundamental to assess the contribution of PAHs to the formation of cosmic H2. PMID- 26821926 TI - Why do you shop there? A mixed methods study mapping household food shopping patterns onto weekly routines of black women. AB - BACKGROUND: The effectiveness of initiatives to increase healthy food access may be affected by where people decide to shop. People with poor neighborhood access to large grocery stores develop shopping patterns that require traveling to other areas, and some people who do have neighborhood access also travel elsewhere for food shopping. We sought to gain an understanding of household food shopping patterns in a sample of Black women in terms of where they shopped and why. METHODS: All food shopping trips of 35 low- or middle/high-income black mothers or caregivers living with at least one child were identified from grocery shopping receipts collected over four consecutive weeks. Food shopping locations were mapped along with locations of participants' homes and other places they visited during weekly routine travels (e.g. work, child's school). Semi structured individual interviews elicited narrative information about whether and how grocery shopping trips were linked to routine travels. Inductive content analysis was utilized to identify emergent themes from interviews. Themes were considered in relation to geospatial distances and travel patterns identified through mapping of participants' shopping. RESULTS: Participants shopped at an average of six different stores, traveling on average a total of 35 miles (sd = 41) (Euclidian distance) over the four weeks. The most frequented store was within a mile of home (57%) or home or another place visited in the weekly routine for about 77% of participants. Interview results emphasized the concept of convenience which referred to geographical proximity to the home or routine destinations and also to potential to save time because several stores were co located or because the store layout was easy to navigate and familiar. Store selection also related to mode of transportation, pricing, and family preference for certain foods. CONCLUSION: People have specific reasons for consistently shopping in areas outside of their neighborhood of residence. Incorporating considerations other than proximity (e.g. time saving while shopping, promoting less familiar foods, pricing) into food environment interventions may facilitate use of new stores by neighborhood residents and thereby increase the viability of these stores as health-promoting food environment interventions. PMID- 26821924 TI - Development of a transgenic mouse model of hepatocellular carcinoma with a liver fibrosis background. AB - BACKGROUND: Liver fibrosis and its end-stage disease, cirrhosis, are major risk factors for hepatocellular carcinoma (HCC) and present in 80 to 90 % of patients with HCC. Current genetically engineered mouse models for HCC, however, generally do not feature liver fibrosis, which is a critical discrepancy between human HCC and murine models thereof. In this study, we developed a simple transgenic mouse model of HCC within the context of a fibrotic liver. METHODS: Employing hydrodynamic transfection (HT), coupled with the Sleeping Beauty (SB) transposon system, liver was stably transfected with transposons expressing cMyc and a short hairpin RNA down-regulating p53 (shp53). A chronic liver injury model, induced by hepatotoxic carbon tetrachloride (CCl4), was applied to the transgenic mice, allowing cells expressing cMyc plus shp53 to become malignant in the background of liver fibrosis. RESULTS: Livers harvested about 3 months after HT had excessive collagen deposition and activated hepatic stellate cells surrounding the tumors. Hepatocarcinogenesis was significantly accelerated in the fibrotic livers compared to those of the control, significantly decreasing the life span of the mice. The tumor incidence and average number of tumors per mouse were significantly higher in the group treated with CCl4 compared to the vehicle treated control mice, following HT (p < 0.01). CONCLUSIONS: Considering the simplicity and efficiency in generating HCC for fibrotic livers, the transgenic HCC model has the potential to be effectively used in preclinical testing of HCC anticancer therapy and in studies of hepatocarcinogenesis in fibrotic livers. PMID- 26821927 TI - Clove bud oil reduces kynurenine and inhibits pqs A gene expression in P. aeruginosa. AB - Quorum sensing (QS), a communication system involved in virulence of pathogenic bacteria like Pseudomonas aeruginosa is a promising target to combat multiple drug resistance. In vitro studies using clove bud oil (CBO) in P. aeruginosa revealed a concentration dependent attenuation of a variety of virulence factors including motility, extracellular DNA, exopolysaccharides and pigment production. Furthermore, treatment with CBO demonstrated a distinct dose-dependent reduction in biofilm formation as well as promoting dispersion of already formed biofilm, observations that were also supported by porcine skin ex vivo studies. Expression studies of genes involved in signalling systems of P. aeruginosa indicated a specific decrease in transcription of pqsA, but not in the lasI or rhlI levels. Additionally, the expression of vfr and gacA genes, involved in regulation, was also not affected by CBO treatment. CBO also influenced the PQS signalling pathway by decreasing the levels of kynurenine, an effect which was reversed by the addition of exogenous kynurenine. Though the synthesis of the signalling molecules of the Las and Rhl pathways was not affected by CBO, their activity was significantly affected, as observed by decrease in levels of their various effectors. Molecular modelling studies demonstrated that eugenol, the major component of CBO, favourably binds to the QS receptor by hydrophobic interactions as well as by hydrogen bonding with Arg61 and Tyr41 which are key amino acid residues of the LasR receptor. These results thus elucidate the molecular mechanism underlying the action of CBO and provide the basis for the identification of an attractive QS inhibitor. PMID- 26821928 TI - Synthesis of human parainfluenza virus 2 nucleocapsid protein in yeast as nucleocapsid-like particles and investigation of its antigenic structure. AB - The aim of this study was to investigate the suitability of yeast Saccharomyces cerevisiae expression system for the production of human parainfluenza virus type 2 (HPIV2) nucleocapsid (N) protein in the form of nucleocapsid-like particles (NLPs) and to characterize its antigenic structure. The gene encoding HPIV2 N amino acid (aa) sequence RefSeq NP_598401.1 was cloned into the galactose inducible S. cerevisiae expression vector and its high-level expression was achieved. However, this recombinant HPIV2 N protein did not form NLPs. The PCR mutagenesis was carried out to change the encoded aa residues to the ones conserved across HPIV2 isolates. Synthesis of the modified proteins in yeast demonstrated that the single aa substitution NP_598401.1:p.D331V was sufficient for the self-assembly of NLPs. The significance of certain aa residues in this position was confirmed by analysing HPIV2 N protein structure models. To characterize the antigenic structure of NLP-forming HPIV2 N protein, a panel of monoclonal antibodies (MAbs) was generated. The majority of the MAbs raised against the recombinant NLPs recognized HPIV2-infected cells suggesting the antigenic similarity between the recombinant and virus-derived HPIV2 N protein. Fine epitope mapping revealed the C-terminal part (aa 386-504) as the main antigenic region of the HPIV2 N protein. In conclusion, the current study provides new data on the impact of HPIV2 N protein sequence variants on the NLP self-assembly and demonstrates an efficient production of recombinant HPIV2 N protein in the form of NLPs. PMID- 26821930 TI - The Role of the Immune System in Ovarian Cancer and Implications on Therapy. AB - Ovarian cancer is the leading cause of death from gynecologic malignancy in the United States. While the treatment options have improved with conventional cytotoxic chemotherapy and advanced surgical techniques, disease recurrence is common and fatal in nearly all cases. Current evidence suggests that the immune system and its ability to recognize and eliminate microscopic disease is paramount in preventing recurrence. The goal of immunotherapy is to balance the activation of the immune system against cancer while preventing the potential for tremendous toxicity elicited by immune modulation. In this paper we will review the role of immune system in disease pathogenesis and different immunotherapies available for the treatment of ovarian cancer as well as current ongoing studies and potential future directions. PMID- 26821929 TI - Expert consensus paper on the use of Vedolizumab for the management of patients with moderate-to-severe Inflammatory Bowel Disease. AB - Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic, relapsing conditions resulting from uncontrolled inflammation of the intestinal mucosa. Both conditions are associated with significant disability and patients with CD face higher mortality rates compared to the general population. The increasing understanding of the immunological basis of the disease led to the introduction of biologic therapies targeting key pathways of the natural and adaptive immune response such as Tumor Necrosis Factor alpha (TNF-alpha) inhibitors and, more recently, integrin-receptor antagonists. Treatment with TNF-alpha inhibitors improved clinical and patient-reported outcomes for many patients who did not benefit from conventional therapy. However, a sizeable share of patients still face suboptimal outcomes due to primary or secondary therapy failure. With the introduction of VDZ, a biologic treatment targeting novel IBD-relevant biologic pathways, it is crucial to understand how to integrate such innovations into current clinical practice. To this end, a panel of 14 Italian experts in the management of IBD met for a roundtable discussion. Recommendations concerning the management of moderate-to-severe IBD based on experts' opinions and literature review are discussed in the present report. PMID- 26821931 TI - Long-term use of lenalidomide and low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: MM-024 Extended Access Program. AB - BACKGROUND: The efficacy and safety of lenalidomide plus low-dose dexamethasone (Rd) in Chinese patients with relapsed/refractory multiple myeloma (RRMM) was demonstrated in a phase 2, multicenter trial (MM-021). MM-024 was an Extended Access Program (EAP) that allowed responding patients in the MM-021 trial to continue to receive Rd, and to provide additional safety and efficacy data with longer follow-up. METHODS: Chinese patients with RRMM who completed >= 1 year of Rd therapy in MM-021 and who remained progression-free under Rd entered the Treatment Phase of the MM-024 EAP, continuing Rd at the same dose and schedule. Patients in MM-021 who discontinued Rd treatment or progressed were allowed to enroll in the Safety Follow-Up Phase of the MM-024 EAP. Safety data, including the incidence of second primary malignancies (SPMs), were collected for >= 5 years from the time the last on-study patient enrolled in the MM-021 trial (primary end point). Efficacy outcomes (time to progression [TTP], progression free survival [PFS], and overall survival [OS]) were secondary end points. RESULTS: Median follow-up was 38.4 months for the safety population (n = 80) and 43.3 months for the treatment cohort (n = 41). In the safety population, Grade 3 4 adverse events (AEs) occurred in 60.0 % of patients; the most common grade 3-4 AEs were neutropenia (20.0%), decreased neutrophil count (13.8%), and anemia (11.3%). There was no evidence of cumulative toxicity, and no patients discontinued Rd due to AEs; 2 patients had SPMs. In the treatment cohort, median duration of response was 35.1 months, median TTP was 36.9 months, and median PFS was 36.0 months; median OS was not reached due to the low number of deaths (n = 5). CONCLUSION: Long-term treatment with Rd has a predictable and manageable safety profile and provides sustained efficacy in Chinese patients with RRMM. TRIAL REGISTRATION: China State Food and Drug Administration (SFDA) registration (CTA reference numbers: 209L10808; 209L10809; 209L10810; and 209L10811) and ClinicalTrials.gov Identifier: NCT02348528. First received January 23, 2015; last updated November 12, 2015; last verified November 2015; study start date September 2012. PMID- 26821932 TI - Theory of antiskyrmions in magnets. AB - Skyrmions and antiskyrmions are swirling topological magnetic textures realized as emergent particles in magnets. A skyrmion is stabilized by the Dzyaloshinskii Moriya interaction in chiral magnets and/or a dipolar interaction in thin film magnets, which prefer the twist of the magnetic moments. Here we show by a numerical simulation of the Landau-Lifshitz-Gilbert equation that pairs of skyrmions and antiskyrmions are created from the helix state as the magnetic field is increased. Antiskyrmions are unstable and disappear immediately in chiral magnets, whereas they are metastable and survive in dipolar magnets. The collision between a skyrmion and an antiskyrmion in a dipolar magnet is also studied. It is found that the collision depends on their relative direction, and the pair annihilation occurs in some cases and only the antiskyrmion is destroyed in the other cases. These results indicate that the antiskyrmion offers a unique opportunity to study particles and antiparticles in condensed-matter systems. PMID- 26821933 TI - The neurotic wandering mind: An individual differences investigation of neuroticism, mind-wandering, and executive control. AB - Cognitive psychology and cognitive neuroscience have recently developed a keen interest in the phenomenon of mind-wandering. People mind-wander frequently, and mind-wandering is associated with decreased cognitive performance. But why do people mind-wander so much? Previous investigations have focused on cognitive abilities like working memory capacity and attention control. But an individual's tendency to worry, feel anxious, and entertain personal concerns also influences mind-wandering. The Control Failure * Concerns model of mind-wandering. Psychological Bulletin, 136, 188-197] argues that individual differences in the propensity to mind-wander are jointly determined by cognitive abilities and by the presence of personally salient concerns that intrude on task focus. In order to test this model, we investigated individual differences in mind-wandering, executive attention, and personality with a focus on neuroticism. The results showed that neurotic individuals tended to report more mind-wandering during cognitive tasks, lower working memory capacity, and poorer attention control. Thus the trait of neuroticism adds an additional source of variance in the tendency to mind-wander, which offers support for the Control Failure * Concerns model. The results help bridge the fields of clinical psychology, cognitive psychology, affective neuroscience, and cognitive neuroscience as a means of developing a more complete understanding of the complex relationship between cognition, personality, and emotion. PMID- 26821935 TI - Differential effects of suppressors on hazardous sound pressure levels generated by AR-15 rifles: Considerations for recreational shooters, law enforcement, and the military. AB - OBJECTIVE: Firearm discharges produce hazardous levels of impulse noise that can lead to permanent hearing loss. In the present study, we evaluated the effects of suppression, ammunition, and barrel length on AR-15 rifles. DESIGN: Sound levels were measured left/right of a user's head, and 1-m left of the muzzle, per MIL STD-1474-D, under both unsuppressed and suppressed conditions. STUDY SAMPLE: Nine commercially available AR-15 rifles and 14 suppressors were used. RESULTS: Suppressors significantly decreased peak dB SPL at the 1-m location and the left ear location. However, under most rifle/ammunition conditions, levels remained above 140 dB peak SPL near a user's right ear. In a subset of conditions, subsonic ammunition produced values near or below 140 dB peak SPL. Overall suppression ranged from 7-32 dB across conditions. CONCLUSIONS: These data indicate that (1) suppressors reduce discharge levels to 140 dB peak SPL or below in only a subset of AR-15 conditions, (2) shorter barrel length and use of muzzle brake devices can substantially increase exposure level for the user, and (3) there are significant left/right ear sound pressure differences under suppressed conditions as a function of the AR-15 direct impingement design that must be considered during sound measurements to fully evaluate overall efficacy. PMID- 26821934 TI - Severe sensory neuropathy in patients with adult-onset multiple acyl-CoA dehydrogenase deficiency. AB - Multiple Acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid oxidation. Most patients with late-onset MADD are clinically characterized by lipid storage myopathy with dramatic responsiveness to riboflavin treatment. Abnormalities of peripheral neuropathy have rarely been reported in patients with late-onset MADD. We describe six patients who presented with proximal limb weakness and loss of sensation in the distal limbs. Muscle biopsy revealed typical myopathological patterns of lipid storage myopathy and blood acylcarnitine profiles showed a combined elevation of multiple acylcarnitines supporting the diagnosis of MADD. However, nerve conduction investigations and sural nerve biopsies in these patients indicated severe axonal sensory neuropathy. Causative ETFDH gene mutations were found in all six cases. No other causative gene mutations were identified in mitochondrial DNA and genes associated with hereditary neuropathies through next-generation-sequencing panel. Late-onset patients with ETFDH mutations can present with proximal muscle weakness and distal sensory neuropathy, which might be a new phenotypic variation, but the precise underlying pathogenesis remains to be elucidated. PMID- 26821936 TI - Comparison of SNP and CAPS markers application in genetic research in wheat and barley. AB - BACKGROUND: Barley and bread wheat show large differences in frequencies of Single Nucleotide Polymorphism (SNP) as determined from genome-wide studies. These frequencies have been estimated as 2.4-3 times higher in the entire barley genome than within each diploid genomes of wheat (A, B or D). However, barley SNPs within individual genes occur significantly more frequently than quoted. Differences between wheat and barley are based on the origin and evolutionary history of the species. Bread wheat contains rarer SNPs due to the double genetic 'bottle-neck' created by natural hybridisation and spontaneous polyploidisation. Furthermore, wheat has the lowest level of useful SNP-derived markers while barley is estimated to have the highest level of polymorphism. RESULTS: Different strategies are required for the development of suitable molecular markers in these cereal species. For example, SNP markers based on high-throughput technology (Infinium or KASP) are very effective and useful in both barley and bread wheat. In contrast, Cleaved Amplified Polymorphic Sequences (CAPS) are more widely and successfully employed in small-scale experiments with highly polymorphic genetic regions containing multiple SNPs in barley, but not in wheat. However, preliminary 'in silico' search databases for assessing the potential value of SNPs have yet to be developed. CONCLUSIONS: This mini-review summarises results supporting the development of different strategies for the application of effective SNP and CAPS markers in wheat and barley. PMID- 26821937 TI - Phase-Controlled Iron Oxide Nanobox Deposited on Hierarchically Structured Graphene Networks for Lithium Ion Storage and Photocatalysis. AB - The phase control, hierarchical architecturing and hybridization of iron oxide is important for achieving multifunctional capability for many practical applications. Herein, hierarchically structured reduced graphene oxide (hrGO)/alpha-Fe2O3 and gamma-Fe3O4 nanobox hybrids (hrGO/alpha-Fe and hrGO/gamma Fe NBhs) are synthesized via a one-pot, hydrothermal process and their functionality controlled by the crystalline phases is adapted for energy storage and photocatalysis. The three-dimensionally (3D) macroporous structure of hrGO/alpha-Fe NBhs is constructed, while alpha-Fe2O3 nanoboxes (NBs) in a proximate contact with the hrGO surface are simultaneously grown during a hydrothermal treatment. The discrete alpha-Fe2O3 NBs are uniformly distributed on the surface of the hrGO/alpha-Fe and confined in the 3D architecture, thereby inhibiting the restacking of rGO. After the subsequent phase transition into gamma-Fe3O4, the hierarchical structure and the uniform distribution of NBs are preserved. Despite lower initial capacity, the hrGO/alpha-Fe NBhs show better rate and cyclic performances than those of commercial rGO/alpha-Fe due to the uniform distribution of discrete alpha-Fe2O3 NBs and electronic conductivity, macroporosity, and buffering effect of the hrGO for lithium ion battery anodes. Moreover, the catalytic activity and kinetics of hrGO/gamma-Fe NBhs are enhanced for photo-Fenton reaction because of the uniform distribution of discrete gamma Fe3O4 NBs on the 3D hierarchical architecture. PMID- 26821938 TI - Typing and selection of wild strains of Trichoderma spp. producers of extracellular laccase. AB - Using the ITS region and the gene tef1, 23 strains of the genus Trichoderma were identified as belonging to the species T. harzianum (n = 14), T. olivascens (n = 1), T. trixiae (n = 1), T. viridialbum (n = 1), T. tomentosum (n = 2), T. koningii (n = 1), T. atroviride (n = 1), T. viride (n = 1), and T. gamsii (n = 1). Strains expressing extracellular laccase activity were selected by decolorization/oxidation assays in solid media, using azo, anthraquinone, indigoid, and triphenylmethane dyes, and the phenolic substances tannic acid and guaiacol. No strain decolorized Direct Blue 71 or Chicago Blue 6B, but all of them weakly oxidized guaiacol, decolorized Methyl Orange, and efficiently oxidized tannic acid. Based in decolorization/oxidation assays, strains CMU-1 (T. harzianum), CMU-8 (T. atroviride), CMU-218 (T. viride), and CMU-221 (T. tomentosum) were selected for evaluating their extracellular laccase activity in liquid media. Strain CMU-8 showed no basal laccase activity, while strains CMU-1, CMU-218, and CMU-221 had a basal laccase activity of 1,313.88 mU/mL, 763.88 mU/mL, and 799.53 mU/mL, respectively. Addition of sorghum straw inhibited laccase activity in strain CMU-1 by 34%, relative to the basal culture, while strains CMU-8, CMU-21, and CMU-221 increased their laccase activity by 1,321.5%, 64%, and 47%, respectively. These results show that assayed phenolic substrates are good tools for selecting laccase producer strains in Trichoderma. These same assays indicate the potential use of studied strains for bioremediation processes. Straw laccase induction suggests that analyzed strains have potential for straw delignification in biopulping and other biotechnological applications. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:787-798, 2016. PMID- 26821940 TI - Boolean Models of Biological Processes Explain Cascade-Like Behavior. AB - Biological networks play a key role in determining biological function and therefore, an understanding of their structure and dynamics is of central interest in systems biology. In Boolean models of such networks, the status of each molecule is either "on" or "off" and along with the molecules interact with each other, their individual status changes from "on" to "off" or vice-versa and the system of molecules in the network collectively go through a sequence of changes in state. This sequence of changes is termed a biological process. In this paper, we examine the common perception that events in biomolecular networks occur sequentially, in a cascade-like manner, and ask whether this is likely to be an inherent property. In further investigations of the budding and fission yeast cell-cycle, we identify two generic dynamical rules. A Boolean system that complies with these rules will automatically have a certain robustness. By considering the biological requirements in robustness and designability, we show that those Boolean dynamical systems, compared to an arbitrary dynamical system, statistically present the characteristics of cascadeness and sequentiality, as observed in the budding and fission yeast cell- cycle. These results suggest that cascade-like behavior might be an intrinsic property of biological processes. PMID- 26821941 TI - Thermal Scanning at the Cellular Level by an Optically Trapped Upconverting Fluorescent Particle. AB - 3D optical manipulation of a thermal-sensing upconverting particle allows for the determination of the extension of the thermal gradient created in the surroundings of a plasmonic-mediated photothermal-treated HeLa cancer cell. PMID- 26821939 TI - Interplay between type IV pili activity and exopolysaccharides secretion controls motility patterns in single cells of Myxococcus xanthus. AB - Myxococcus xanthus performs coordinated social motility of cell groups through the extension and retraction of type IV pili (TFP) on solid surfaces, which requires both TFP and exopolysaccharides (EPS). By submerging cells in a liquid medium containing 1% methylcellulose, M. xanthus TFP-driven motility was induced in isolated cells and independently of EPS. We measured and analyzed the movements of cells using community tracking algorithms, which combine single-cell resolution with statistics from large sample populations. Cells without significant multi-cellular social interactions have surprisingly complex behaviors: EPS(-) cells exhibited a pronounced increase in the tendency to stand vertically and moved with qualitatively different characteristics than other cells. A decrease in the EPS secretion of cells correlates with a higher instantaneous velocity, but with lower directional persistence in trajectories. Moreover, EPS(-) cells do not adhere to the surface as strongly as wild-type and EPS overproducing cells, and display a greater tendency to have large deviations between the direction of movement and the cell axis, with cell velocity showing only minimal dependence on the direction of movement. The emerging picture is that EPS does not simply provide rheological resistance to a single mechanism but rather that the availability of EPS impacts motility pattern. PMID- 26821942 TI - Antidepressants may double risk of suicide and aggression in children, study finds. PMID- 26821943 TI - Nonradiative Electron--Hole Recombination Rate Is Greatly Reduced by Defects in Monolayer Black Phosphorus: Ab Initio Time Domain Study. AB - We report ab initio time-domain simulations of nonradiative electron-hole recombination and electronic dephasing in ideal and defect-containing monolayer black phosphorus (MBP). Our calculations predict that the presence of phosphorus divacancy in MBP (MBP-DV) substantially reduces the nonradiative recombination rate, with time scales on the order of 1.57 ns. The luminescence line width in ideal MBP of 150 meV is 2.5 times larger than MBP-DV at room temperature, and is in excellent agreement with experiment. We find that the electron-hole recombination in ideal MBP is driven by the 450 cm(-1) vibrational mode, whereas the recombination in the MBP-DV system is driven by a broad range of vibrational modes. The reduced electron-phonon coupling and increased bandgap in MBP-DV rationalize slower recombination in this material, suggesting that electron phonon energy losses in MBP can be minimized by creating suitable defects in semiconductor device material. PMID- 26821944 TI - Blockade of Tim-1 and Tim-4 Enhances Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice. AB - OBJECTIVE: T cell immunoglobulin and mucin domain (Tim) proteins are expressed by numerous immune cells, recognize phosphatidylserine on apoptotic cells, and function as costimulators or coinhibitors. Tim-1 is expressed by activated T cells but is also found on dendritic cells and B cells. Tim-4, present on macrophages and dendritic cells, plays a critical role in apoptotic cell clearance, regulates the number of phosphatidylserine-expressing activated T cells, and is genetically associated with low low-density lipoprotein and triglyceride levels. Because these functions of Tim-1 and Tim-4 could affect atherosclerosis, their modulation has potential therapeutic value in cardiovascular disease. APPROACH AND RESULTS: ldlr(-/-) mice were fed a high-fat diet for 4 weeks while being treated with control (rat immunoglobulin G1) or anti Tim-1 (3D10) or -Tim-4 (21H12) monoclonal antibodies that block phosphatidylserine recognition and phagocytosis. Both anti-Tim-1 and anti-Tim-4 treatments enhanced atherosclerosis by 45% compared with controls by impairment of efferocytosis and increasing aortic CD4(+)T cells. Consistently, anti-Tim-4 treated mice showed increased percentages of activated T cells and late apoptotic cells in the circulation. Moreover, in vitro blockade of Tim-4 inhibited efferocytosis of oxidized low-density lipoprotein-induced apoptotic macrophages. Although anti-Tim-4 treatment increased T helper cell (Th)1 and Th2 responses, anti-Tim-1 induced Th2 responses but dramatically reduced the percentage of regulatory T cells. Finally, combined blockade of Tim-1 and Tim-4 increased atherosclerotic lesion size by 59%. CONCLUSIONS: Blockade of Tim-4 aggravates atherosclerosis likely by prevention of phagocytosis of phosphatidylserine expressing apoptotic cells and activated T cells by Tim-4-expressing cells, whereas Tim-1-associated effects on atherosclerosis are related to changes in Th1/Th2 balance and reduced circulating regulatory T cells. PMID- 26821945 TI - Extracellular Vesicles Activate a CD36-Dependent Signaling Pathway to Inhibit Microvascular Endothelial Cell Migration and Tube Formation. AB - OBJECTIVE: Literature on the effect of cell-derived extracellular vesicles (EV), <=1 MUm vesicles shed from various cell types during activation or apoptosis, on microvascular endothelial cell (MVEC) signaling is conflicting. Thrombospondin-1 and related proteins induce anti-angiogenic signals in MVEC via CD36. CD36 binds EV via phosphatidylserine exposed on their surface but the effects of this interaction on MVEC functions are not known. We hypothesized that EV would inhibit angiogenic MVEC functions via CD36. APPROACH AND RESULTS: EV generated in vitro from various cell types or isolated from plasma inhibited MVEC tube formation in in vitro matrigel assays and endothelial cell migration in Boyden chamber assays. Exosomes derived from the same cells did not have inhibitory activity. Inhibition of migration required endothelial cell expression of CD36. In mouse in vivo matrigel plug assays, EV inhibited cell migration into matrigel plugs in wild type but not in cd36 null animals. Annexin V, an anionic phospholipid binding protein, when incubated with EV partially reversed inhibition of migration, suggesting a phosphatidylserine-dependent effect. EV exposure induced reactive oxygen species generation in MVEC in a NADPH oxidase and Src family kinase-dependent manner, and their inhibition by apocynin and PP2, respectively, partially reversed the EV-mediated inhibition of migration. Annexin V partially reversed EV-induced reactive oxygen species generation in murine CD36 cDNA-transfected HVUEC but not in CD36-negative human umbilical vein endothelial cell. CONCLUSIONS: These studies establish a general inhibitory effect of EV on endothelial cell proangiogenic responses and identify a CD36-mediated mechanistic pathway through which EV inhibit MVEC migration and tube formation. PMID- 26821947 TI - Pioglitazone-Incorporated Nanoparticles Prevent Plaque Destabilization and Rupture by Regulating Monocyte/Macrophage Differentiation in ApoE-/- Mice. AB - OBJECTIVE: Inflammatory monocytes/macrophages produce various proteinases, including matrix metalloproteinases, and degradation of the extracellular matrix by these activated proteinases weakens the mechanical strength of atherosclerotic plaques, which results in a rupture of the plaque. Peroxisome proliferator activated receptor-gamma induces a polarity shift of monocytes/macrophages toward less inflammatory phenotypes and has the potential to prevent atherosclerotic plaque ruptures. Therefore, we hypothesized that nanoparticle-mediated targeted delivery of the peroxisome proliferator-activated receptor-gamma agonist pioglitazone into circulating monocytes could effectively inhibit plaque ruptures in a mouse model. APPROACH AND RESULTS: We prepared bioabsorbable poly(lactic-co glycolic-acid) nanoparticles containing pioglitazone (pioglitazone-NPs). Intravenously administered poly(lactic-co-glycolic-acid) nanoparticles incorporated with fluorescein isothiocyanate were found in circulating monocytes and aortic macrophages by flow cytometric analysis. Weekly intravenous administration of pioglitazone-NPs (7 mg/kg per week) for 4 weeks decreased buried fibrous caps, a surrogate marker of plaque rupture, in the brachiocephalic arteries of ApoE(-/-) mice fed a high-fat diet and infused with angiotensin II. In contrast, administration of control-NPs or an equivalent dose of oral pioglitazone treatment produced no effects. Pioglitazone-NPs inhibited the activity of matrix metalloproteinases and cathepsins in the brachiocephalic arteries. Pioglitazone-NPs regulated inflammatory cytokine expression and also suppressed the expression of extracellular matrix metalloproteinase inducer in bone marrow-derived macrophages. CONCLUSIONS: Nanoparticle-mediated delivery of pioglitazone inhibited macrophage activation and atherosclerotic plaque ruptures in hyperlipidemic ApoE(-/-) mice. These results demonstrate a promising strategy with a favorable safety profile to prevent atherosclerotic plaque ruptures. PMID- 26821946 TI - 2015 Russell Ross Memorial Lecture in Vascular Biology: Protective Autoimmunity in Atherosclerosis. AB - Atherosclerosis is an inflammatory disease of the arterial wall. It is accompanied by an autoimmune response against apolipoprotein B-100, the core protein of low-density lipoprotein, which manifests as CD4 T cell and antibody responses. To assess the role of the autoimmune response in atherosclerosis, the nature of the CD4 T cell response against apolipoprotein B-100 was studied with and without vaccination with major histocompatibility complex-II-restricted apolipoprotein B-100 peptides. The immunologic basis of autoimmunity in atherosclerosis is discussed in the framework of theories of adaptive immunity. Older vaccination approaches are also discussed. Vaccinating Apoe(-/-) mice with major histocompatibility complex-II-restricted apolipoprotein B-100 peptides reduces atheroma burden in the aorta by ~40%. The protective mechanism likely includes secretion of interleukin-10. Protective autoimmunity limits atherosclerosis in mice and suggests potential for developing preventative and therapeutic vaccines for humans. PMID- 26821948 TI - Interaction Between ALK1 Signaling and Connexin40 in the Development of Arteriovenous Malformations. AB - OBJECTIVE: To determine the role of Gja5 that encodes for the gap junction protein connexin40 in the generation of arteriovenous malformations in the hereditary hemorrhagic telangiectasia type 2 (HHT2) mouse model. APPROACH AND RESULTS: We identified GJA5 as a target gene of the bone morphogenetic protein 9/activin receptor-like kinase 1 signaling pathway in human aortic endothelial cells and importantly found that connexin40 levels were particularly low in a small group of patients with HHT2. We next took advantage of the Acvrl1(+/-) mutant mice that develop lesions similar to those in patients with HHT2 and generated Acvrl1(+/-); Gja5(EGFP/+) mice. Gja5 haploinsufficiency led to vasodilation of the arteries and rarefaction of the capillary bed in Acvrl1(+/-) mice. At the molecular level, we found that reduced Gja5 in Acvrl1(+/-) mice stimulated the production of reactive oxygen species, an important mediator of vessel remodeling. To normalize the altered hemodynamic forces in Acvrl1(+/-); Gja5(EGFP/+) mice, capillaries formed transient arteriovenous shunts that could develop into large malformations when exposed to environmental insults. CONCLUSIONS: We identified GJA5 as a potential modifier gene for HHT2. Our findings demonstrate that Acvrl1 haploinsufficiency combined with the effects of modifier genes that regulate vessel caliber is responsible for the heterogeneity and severity of the disease. The mouse models of HHT have led to the proposal that 3 events-heterozygosity, loss of heterozygosity, and angiogenic stimulation are necessary for arteriovenous malformation formation. Here, we present a novel 3-step model in which pathological vessel caliber and consequent altered blood flow are necessary events for arteriovenous malformation development. PMID- 26821949 TI - Evidence That Cingulin Regulates Endothelial Barrier Function In Vitro and In Vivo. AB - OBJECTIVE: Cingulin is a cytoplasmic component of tight junctions. Although modulation of cingulin levels in cultured epithelial model systems has no significant effect on barrier function, evidence from cingulin knockout mice suggests that cingulin may be involved in the regulation of the behavior of epithelial or endothelial cells. Here, we investigate the role of cingulin in the barrier function of endothelial cells. APPROACH AND RESULTS: We show that cingulin is expressed in human endothelial cells of the skin, brain, and lung in vivo and in vitro. Endothelial cingulin colocalizes and coimmunoprecipitates with the tight junction proteins zonula occludens-1 and guanine nucleotide exchange factor-H1. Cingulin overexpression in human umbilical vein endothelial cell induces tight junction formation, increases transendothelial electric resistance, and strengthens barrier function for low and high molecular weight tracers. In contrast, cultured endothelial cells lacking cingulin are more permeable for low molecular weight tracers. In cingulin knockout mice, neurons of the area postrema and Purkinje cells show an increased uptake of small molecular weight tracers indicating decreased barrier function at these sites. CONCLUSIONS: We demonstrate that cingulin participates in the modulation of endothelial barrier function both in human cultured cells in vitro and in mouse brains in vivo. Understanding the role of cingulin in maintaining tight barriers in endothelia may allow developing new strategies for the treatment of vascular leak syndromes. PMID- 26821950 TI - Platelet CD40 Exacerbates Atherosclerosis by Transcellular Activation of Endothelial Cells and Leukocytes. AB - OBJECTIVE: Beyond their eminent role in hemostasis and thrombosis, platelets are recognized as mediators of inflammation. Platelet cluster of differentiation 40 (CD40) ligand (CD40L and CD154) plays a key role in mediating platelet-induced inflammation in atherosclerosis. CD40, the receptor for CD40L, is present on platelets; however, the role of CD40 on this cell type is until now undefined. APPROACH AND RESULTS: We found that in both mice and humans, platelet CD40 mediates the formation of platelet-leukocyte aggregates and the release of chemokine (C-X-C motif) ligand 4. Leukocytes were also less prone to adhere to CD40-deficient thrombi. However, platelet CD40 was not involved in platelet aggregation. Activated platelets isolated from Cd40(-/-)Apoe(-/-) mice adhered less to the endothelium upon injection into Apoe(-/-) mice when compared with CD40-sufficient platelets. Furthermore, lack of CD40 on injected platelets led to reduced leukocyte recruitment to the carotid artery as assayed by intravital microscopy. This was accompanied by a decrease in endothelial vascular cell adhesion molecule-1, platelet endothelial cell adhesion molecule, VE-cadherin, and P-selectin expression. To investigate the effect of platelet CD40 in atherosclerosis, Apoe(-/-) mice received thrombin-activated Apoe(-/-) or Cd40(-/ )Apoe(-/-) platelets every 5 days for 12 weeks, starting at the age of 17 weeks, when atherosclerotic plaques had already formed. When compared with mice that received Apoe(-/-) platelets, those receiving Cd40(-/-)Apoe(-/-) platelets exhibited a >2-fold reduction in atherosclerosis. Plaques of mice receiving CD40 deficient platelets were less advanced, contained less macrophages, neutrophils, and collagen, and displayed smaller lipid cores. CONCLUSIONS: Platelet CD40 plays a crucial role in inflammation by stimulating leukocyte activation and recruitment and activation of endothelial cells, thereby promoting atherosclerosis. PMID- 26821951 TI - Aminoacyl-Transfer RNA Synthetase Deficiency Promotes Angiogenesis via the Unfolded Protein Response Pathway. AB - OBJECTIVE: Understanding the mechanisms regulating normal and pathological angiogenesis is of great scientific and clinical interest. In this report, we show that mutations in 2 different aminoacyl-transfer RNA synthetases, threonyl tRNA synthetase (tars(y58)) or isoleucyl tRNA synthetase (iars(y68)), lead to similar increased branching angiogenesis in developing zebrafish. APPROACH AND RESULTS: The unfolded protein response pathway is activated by aminoacyl-transfer RNA synthetase deficiencies, and we show that unfolded protein response genes atf4, atf6, and xbp1, as well as the key proangiogenic ligand vascular endothelial growth factor (vegfaa), are all upregulated in tars(y58) and iars(y68) mutants. Finally, we show that the protein kinase RNA-like endoplasmic reticulum kinase-activating transcription factor 4 arm of the unfolded protein response pathway is necessary for both the elevated vegfaa levels and increased angiogenesis observed in tars(y58) mutants. CONCLUSIONS: Our results suggest that endoplasmic reticulum stress acts as a proangiogenic signal via unfolded protein response pathway-dependent upregulation of vegfaa. PMID- 26821952 TI - Weak signal detection: A discrete window of opportunity for achieving 'Vision 90:90:90'? AB - INTRODUCTION: UNAIDS' Vision 90:90:90 is a call to 'end AIDS'. Developing predictive foresight of the unpredictable changes that this journey will entail could contribute to the ambition of 'ending AIDS'. There are few opportunities for managing unpredictable changes. We introduce 'weak signal detection' as a potential opportunity to fill this void. METHOD: Combining futures and complexity theory, we reflect on two pilot case studies that involved the Archetype Extraction technique and the SenseMaker((r)) Collector(TM) tool. RESULTS: Both the piloted techniques have the potentials to surface weak signals--but there is room for improvement. DISCUSSION: A management response to a complex weak signal requires pattern management, rather than an exclusive focus on behaviour management. CONCLUSION: Weak signal detection is a window of opportunity to improve resilience to unpredictable changes in the HIV/AIDS landscape that can both reduce the risk that emerges from the changes and increase the visibility of opportunities to exploit the unpredictable changes that could contribute to 'ending AIDS'. PMID- 26821953 TI - Inpatient Pressure Ulcer Prevalence in an Acute Care Hospital Using Evidence Based Practice. AB - BACKGROUND: A national goal was set in 2004 for decreasing hospital-acquired pressure ulcers (HAPUs). A mean to achieve that goal was initiated in 2005 with long-term care facilities. Acute care facilities, with encouragement from the Centers for Medicare and Medicaid Services, took action. AIMS: Pressure ulcer prevention efforts at MaineGeneral Medical Center (MGMC), a 192-bed acute care hospital in Augusta, Maine, sought to reduce HAPU prevalence from a mean of 7.8% in 2005. METHODS: A retrospective study over a 10-year period, from 2005 through 2014, tracked HAPUs and evidence-based practice (EBP) initiatives to decrease the annual mean prevalence rate. RESULTS: The annual mean HAPU prevalence rate of 7.8% in 2005 decreased to 1.4% in 2011, then maintaining this level through 2014 at MGMC. Evidence-based practices for pressure ulcer prevention were implemented using data collection tools from the National Database of Nursing Quality Indicators; guidelines from the National Pressure Ulcer Advisory Panel; and procedural guidance tools from the 5 Million Lives Campaign and the Agency for Healthcare Research and Quality. CONCLUSIONS: Accurate data collection methods and evidence-based guidelines are vital to improving care; yet planning with annual review, fostering an EBP culture, by-in of stakeholders, and education, are the means to long-term consistent implementation of pressure ulcer prevention measures. LINKING EVIDENCE TO ACTION: Keys to decreasing and maintaining the rate were based on effective scientific evidence for prevention of pressure ulcers: assessment tools, education, planning guidance, documentation, and evidence-based practice guidelines. PMID- 26821954 TI - Interventions to aid patient adherence to physiotherapist prescribed self management strategies: a systematic review. AB - BACKGROUND: Physiotherapist prescribed self-management strategies are an important adjunct to 'hands on' treatment. However, treatment outcomes are likely to be related to whether patients adhere to the prescribed strategy. Therefore, physiotherapists should be aware of adherence aiding interventions designed to maximise patient outcomes underpinned by quality research studies. OBJECTIVE: To conduct a systematic review of the interventions used to aid patient adherence to all physiotherapist prescribed self-management strategies. DATA SOURCES: The search included the databases CINAHL, EMBASE, MEDLINE, PUBMED, PSYCINFO, SPORTSDiscus, the Cochrane Central Register of Controlled Trials, PEDro and Mednar for randomised controlled trials (RCTs) published in a peer reviewed journal from inception to November 2014. DATA EXTRACTION AND SYNTHESIS: Data were extracted using a standardised form from twelve included RCTs for patient adherence rates to self-management strategies for interventions used to aid patient adherence and usual care. Two independent reviewers conducted methodological quality assessment. RESULTS: Twelve different interventions to aid patient adherence to exercise were recorded from twelve fair to high quality RCTs. Potential adherence aiding interventions include an activity monitor and feedback system, written exercise instructions, behavioural exercise programme with booster sessions and goal setting. CONCLUSION AND IMPLICATIONS OF KEY FINDINGS: Despite a number of studies demonstrating interventions to positively influence patient adherence to exercise, there is insufficient data to endorse their use in clinical practice. No RCTs examining adherence aiding interventions to self-management strategies other than exercise were identified, indicating a significant gap in the literature. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42015014516. PMID- 26821955 TI - Behavioral Economics, Wearable Devices, and Cooperative Games: Results From a Population-Based Intervention to Increase Physical Activity. AB - BACKGROUND: Health care literature supports the development of accessible interventions that integrate behavioral economics, wearable devices, principles of evidence-based behavior change, and community support. However, there are limited real-world examples of large scale, population-based, member-driven reward platforms. Subsequently, a paucity of outcome data exists and health economic effects remain largely theoretical. To complicate matters, an emerging area of research is defining the role of Superusers, the small percentage of unusually engaged digital health participants who may influence other members. OBJECTIVE: The objective of this preliminary study is to analyze descriptive data from GOODcoins, a self-guided, free-to-consumer engagement and rewards platform incentivizing walking, running and cycling. Registered members accessed the GOODcoins platform through PCs, tablets or mobile devices, and had the opportunity to sync wearables to track activity. Following registration, members were encouraged to join gamified group challenges and compare their progress with that of others. As members met challenge targets, they were rewarded with GOODcoins, which could be redeemed for planet- or people-friendly products. METHODS: Outcome data were obtained from the GOODcoins custom SQL database. The reporting period was December 1, 2014 to May 1, 2015. Descriptive self-report data were analyzed using MySQL and MS Excel. RESULTS: The study period includes data from 1298 users who were connected to an exercise tracking device. Females consisted of 52.6% (n=683) of the study population, 33.7% (n=438) were between the ages of 20-29, and 24.8% (n=322) were between the ages of 30-39. 77.5% (n=1006) of connected and active members met daily-recommended physical activity guidelines of 30 minutes, with a total daily average activity of 107 minutes (95% CI 90, 124). Of all connected and active users, 96.1% (n=1248) listed walking as their primary activity. For members who exchanged GOODcoins, the mean balance was 4,000 (95% CI 3850, 4150) at time of redemption, and 50.4% (n=61) of exchanges were for fitness or outdoor products, while 4.1% (n=5) were for food-related items. Participants were most likely to complete challenges when rewards were between 201-300 GOODcoins. CONCLUSIONS: The purpose of this study is to form a baseline for future research. Overall, results indicate that challenges and incentives may be effective for connected and active members, and may play a role in achieving daily-recommended activity guidelines. Registrants were typically younger, walking was the primary activity, and rewards were mainly exchanged for fitness or outdoor products. Remaining to be determined is whether members were already physically active at time of registration and are representative of healthy adherers, or were previously inactive and were incentivized to change their behavior. As challenges are gamified, there is an opportunity to investigate the role of superusers and healthy adherers, impacts on behavioral norms, and how cooperative games and incentives can be leveraged across stratified populations. Study limitations and future research agendas are discussed. PMID- 26821956 TI - Which Is Better for Arthroscopic Tenodesis of the Long Head of the Biceps: Soft Tissue or Bony Interference Fixation? AB - PURPOSE: To compare the outcome between arthroscopic soft tissue tenodesis (STT) at the rotator interval and bony interference fixation tenodesis (BIFT) at the distal bicipital groove for the long head of the biceps (LHB). METHODS: Twenty five shoulders that underwent arthroscopic STT of the LHB were compared with 28 shoulders that underwent arthroscopic BIFT using a 5.5-mm Bio-Tenodesis screw (Arthrex, Naples, FL). American Shoulder and Elbow Surgeons scores, Constant score, and elbow flexion strength index (EFSI) were checked preoperatively, postoperative 1 year and 2 years. Ultrasound imaging evaluation took place at 1 year and 2 years postoperatively as well. RESULTS: The overall functional outcomes improved after surgery in both groups. The BIFT group showed a significant increase in EFSI (preop: 0.54, postoperative 2 years: 0.94) compared with that of the STT group (preop: 0.52, postoperative 2 years: 0.74) at postoperative 2 years (P = .006). However, no significant difference was seen in the increase of American Shoulder and Elbow Surgeons scores and Constant scores between the two groups. At postoperative 2 years, ultrasound showed seven empty grooves in the STT group, but only two empty grooves in the BIFT group (P = .046). CONCLUSIONS: Arthroscopic BIFT for the LHB showed better improvement in EFSI than arthroscopic STT. In addition, the STT group showed a higher failure rate than the BIFT group. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 26821957 TI - Factors Associated With High-Grade Lachman, Pivot Shift, and Anterior Drawer at the Time of Anterior Cruciate Ligament Reconstruction. AB - PURPOSE: To determine which patient and injury factors are associated with the detection of high-grade laxity on examination under anesthesia before anterior cruciate ligament (ACL) reconstruction. METHODS: We identified 2,318 patients who underwent primary ACL reconstruction without associated ligament injuries. Demographic data and information regarding meniscal tears were collected. Patients with high-grade Lachman (difference from contralateral side >10 mm), pivot-shift (International Knee Documentation Committee grade 3+), or anterior drawer (difference from contralateral side >10 mm) tests were identified by physical examination under anesthesia before ACL reconstruction. Logistic regression modeling was used to evaluate whether chronicity of the ACL injury, patient age, sex, body mass index, generalized ligamentous laxity, and presence of meniscal tears were associated with increased odds of high-grade laxity, while we controlled for examining surgeon. RESULTS: Patients with chronic tears (>6 months from injury) had greater than twice the odds of having high-grade Lachman, pivot-shift, and anterior drawer tests (all P < .001) relative to patients with acute tears (<3 months from injury). Generalized ligamentous laxity (odds ratio [OR], 2.33; P < .001) and the presence of medial (OR, 1.63; P < .001) or lateral (OR, 1.41; P = .013) meniscus tears were associated with increased odds of a high grade Lachman test. Age younger than 20 years (OR, 1.34; P = .023), female sex (OR, 1.49; P = .001), generalized ligamentous laxity (OR, 3.46; P < .001), and the presence of a medial (OR, 1.53; P < .001) or lateral (OR, 1.27; P = .041) meniscus tear were associated with increased odds of a high-grade pivot-shift test. Generalized ligamentous laxity (OR, 2.27; P < .001) and the presence of a medial (OR, 1.73; P = .001) or lateral (OR, 1.50; P = .010) meniscus tear were associated with increased odds of a high-grade anterior drawer test. CONCLUSIONS: Chronic ACL tears, generalized ligamentous laxity, and meniscus tears are associated with increased odds of high-grade laxity with all 3 tests. Female patients and age younger than 20 years are associated with increased odds of a high-grade pivot-shift test. LEVEL OF EVIDENCE: Level II, lesser-quality prospective study. PMID- 26821958 TI - Effect of Teres Minor Fatty Infiltration on Rotator Cuff Repair Outcomes. AB - PURPOSE: To observe changes in fatty infiltration (FI) of the teres minor without tear of the teres minor in a postoperative magnetic resonance imaging and to evaluate the influence of FI of the teres minor in the clinical outcomes of rotator cuff repair. METHODS: Of 816 patients who underwent rotator cuff repair, 51 (6.3%) had FI of the teres minor without tear involvement and 30 cases were available for postoperative magnetic resonance imaging. FI and functional outcome scores were assessed and compared with the control group that had no FI of the teres minor selected by a propensity score matching. RESULTS: FI of the teres minor was observed in various degrees (grade 1 in 9, grade 2 in 9, grade 3 in 6, and grade 4 in 6). The degree of FI was not related to the amount of tendon involvement of a rotator cuff tear (P = .240). All postoperative functional outcome scores (12.6 +/- 1.2 months; range, 11-17), including pain visual analog scale, Simple Shoulder Test, and American Shoulder and Elbow Surgeons Score, significantly improved (all P < .001), and there were no significant differences compared with that of the control group. In most of the cases, FI of the teres minor was unchanged (P = .317). CONCLUSIONS: FI of the teres minor without tear involvement can be observed in a rotator cuff tear as a possibly incidental finding of unknown clinical significance. Its cause has not been determined, and it appears that FI of the teres minor does not appear to improve, at least at the 1-year follow-up. Nevertheless, the functional outcomes of the repair were successful in our study; therefore, rotator cuff repair can be performed without a great deal of concern in the presence of FI in the teres minor. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 26821959 TI - Triple-Loaded Single-Row Versus Suture-Bridge Double-Row Rotator Cuff Tendon Repair With Platelet-Rich Plasma Fibrin Membrane: A Randomized Controlled Trial. AB - PURPOSE: To compare the structural healing and clinical outcomes of triple-loaded single-row with suture-bridging double-row repairs of full-thickness rotator cuff tendons when both repair constructs are augmented with platelet-rich plasma fibrin membrane. METHODS: A prospective, randomized, consecutive series of patients diagnosed with full-thickness rotator cuff tears no greater than 3 cm in anteroposterior length were treated with a triple-loaded single-row (20) or suture-bridging double-row (20) repair augmented with platelet-rich plasma fibrin membrane. The primary outcome measure was cuff integrity by magnetic resonance imaging (MRI) at 12 months postoperatively. Secondary clinical outcome measures were American Shoulder and Elbow Surgeons, Rowe, Simple Shoulder Test, Constant, and Single Assessment Numeric Evaluation scores. RESULTS: The mean MRI interval was 12.6 months (range, 12-17 months). A total of 3 of 20 single-row repairs and 3 of 20 double-row repairs (15%) had tears at follow-up MRI. The single-row group had re-tears in 1 single tendon repair and 2 double tendon repairs. All 3 tears failed at the original attachment site (Cho type 1). In the double-row group, re tears were found in 3 double tendon repairs. All 3 tears failed medial to the medial row near the musculotendinous junction (Cho type 2). All clinical outcome measures were significantly improved from the preoperative level (P < .0001), but there was no statistical difference between groups postoperatively. CONCLUSIONS: There is no MRI difference in rotator cuff tendon re-tear rate at 12 months postsurgery between a triple-loaded single-row repair or a suture-bridging double row repair when both are augmented with platelet-rich plasma fibrin membrane. No difference could be demonstrated between these repairs on clinical outcome scores. LEVEL OF EVIDENCE: I, Prospective randomized study. PMID- 26821960 TI - Outcomes of Revision Hip Arthroscopy: 2-Year Clinical Follow-up. AB - PURPOSE: To evaluate clinical outcomes, pain, and patient satisfaction following revision hip arthroscopy with a minimum 2-year follow-up. METHODS: From April 2008 to October 2011, data were prospectively collected on all patients undergoing revision hip arthroscopy. All patients were assessed pre- and postoperatively with 4 patient-reported outcome (PRO) measures: the modified Harris hip score (mHHS), nonarthritic hip score (NAHS), hip outcome score activities of daily living (HOS-ADL), and hip outcome score-sport-specific subscales (HOS-SSS). Pain was estimated on the visual analog scale (VAS). Patient satisfaction was measured on a scale from 0 to 10. The number of patients who underwent subsequent revision arthroscopy or total hip arthroplasty during the study period is also reported. RESULTS: Eighty-seven patients underwent revision hip arthroscopy during the study period. Seventy (80.5%) patients were included in our study. Average follow-up time was 28 months (range, 20 to 47.4 months). In terms of residual femoroacetabular impingement morphology, 45.7% of patients had preoperative alpha angles >= 55 degrees , and 7.14% of patients had a lateral center-edge angle >= 40 degrees . The score improvement from preoperative to 2 year follow-up was 57.84 to 73.65 for mHHS, 62.79 to 83.04 for HOS-ADL, 37.33 to 54.93 for HOS-SSS, and 55.65 to 70.79 for NAHS. VAS decreased from 6.72 to 4.08. All scores demonstrated statistically significant improvement (P < .001). Overall patient satisfaction was 7.67. Our success rate was 74.58%. Ten (14.29%) patients underwent total hip arthroplasty during the study period. Our hip survivorship was 85.7%. Five (7.14%) patients underwent secondary revision hip arthroscopy during the study period. We found an overall minor complication rate of 10%. CONCLUSIONS: Revision hip arthroscopy for all procedures performed on aggregate has improved clinical outcomes for all PROs, high survivorship, and high patient satisfaction scores at short-term follow-up. Patients should be counseled regarding the potential progression of degenerative change leading to arthroplasty and the potential for revision surgery. LEVEL OF EVIDENCE: Level IV retrospective case series. PMID- 26821961 TI - Trends in Arthroscopic Procedures Performed During Orthopaedic Residency: An Analysis of Accreditation Council for Graduate Medical Education Case Log Data. AB - PURPOSE: To analyze orthopaedic resident case log data to report temporal trends in performing arthroscopic procedures and to assess variability in arthroscopic case volume among residents. METHODS: Accreditation Council for Graduate Medical Education orthopaedic surgery resident case logs were reviewed from 2007 to 2013. The mean number of wrist, elbow, shoulder, knee, and ankle arthroscopic procedures performed by graduating residents was analyzed. The median number of arthroscopic procedures reported by the 70th and 30th percentiles of graduating residents (by arthroscopic case volume) was also recorded. Temporal trends were assessed using a linear regression model. RESULTS: From 2007 to 2013, there were significant increases in the mean number of wrist (5.8 to 6.3; P = .038), elbow (2.5 to 3.2; P < .001), shoulder (93.5 to 133.8; P < .001), knee (170.6 to 185.1; P = .011), and ankle (5.8 to 7.4; P < .001) arthroscopies performed per resident. Residents in the 70th percentile of caseload performed significantly more wrist (7 v 2; P < .001), elbow (3.3 v 1; P < .001), shoulder (134.1 v 70.6; P < .001), knee (205 v 128.7; P < .001), and ankle (7.9 v 2.9; P < .001) arthroscopies than residents in the 30th percentile. CONCLUSIONS: Our findings indicate that arthroscopic caseload is increasing among orthopaedic residents. However, resident experience performing arthroscopic procedures is substantially disparate. Although the educational implications of this disparity are not well understood, our findings may aid in efforts to optimize arthroscopic training during orthopaedic residency. PMID- 26821962 TI - An Arthroscopic Second-Look Study on the Effect of Remnant Preservation on Synovialization of Bone-Patellar Tendon-Bone Allograft in Anterior Cruciate Ligament Reconstruction. AB - PURPOSE: To assess the effects of preserved more anterior cruciate ligament (ACL) remnant on synovial coverage, knee stability, and function after bone patellar tendon-bone (BPTB) allograft reconstruction through second-look arthroscopy and follow-up study. METHODS: From June 2007 to February 2009, 51 patients received single bundle BPTB allograft ACL reconstruction and second arthroscopic examination. The patients were divided into 4 types according to the types of ACL remnant: type 1, 18 had bridging between the posterior cruciate ligament and the tibia; type 2, 21 had bridging between the intercondylar notch roof and the tibia; type 3, 4 had bridging between the lateral condyle and the tibia; and type 4, 8 subjects had no ACL remnants. Clinical results were evaluated with the KT 1000 maximum displacement test and Lysholm scale at mean 12.3- and 53.5-month follow-up. Second-look synovium coverage was recorded as follows: covering 25% or less, 25% to 50%, 50% to 75%, and more than 75%. RESULTS: Mean percentage of synovium coverage, Lysholm scale, and KT-1000 side-to-side difference were poorer in types 3 and 4 than the other 2 types at mean 12.3-month follow-up without statistical differences. The result of the final follow-up was comparable with the first one. Four patients had ruptured grafts and accepted revision surgery. Three of them belonged to types 3 and 4, and 1 patient with sport trauma belonged to type 2. There were other 11 patients with different types of impingement and partial absorption of grafts. CONCLUSIONS: Although lack of statistical power, follow-up study and second-look arthroscopy showed that preserved type 3 and 4 ACL remnant caused poorer synovium coverage and might lead to earlier failure when using BPTB allograft. Early minor laxity at 12.3-month follow-up seemed to be not progressive at the final follow-up. LEVEL OF EVIDENCE: Level III, case control study. PMID- 26821963 TI - Treatment of cutaneous lupus erythematosus: current practice variations. AB - The treatment of cutaneous lupus erythematous (CLE) remains a challenge. Most of the therapeutic options used in CLE have not been tested in randomized controlled studies and to date no agent has been approved. Therefore, CLE treatment is mostly based on personal experience. To better characterize therapeutic habits among physicians treating CLE patients, a questionnaire-based study about various aspects of topical and systemic treatment for CLE has been performed. The questionnaire was distributed among CLE experts, mostly from Japan, the USA, and Europe. A total of 82 completed questionnaires were assessed. High-potent and potent corticosteroids as well as calcineurin inhibitors were the most often recommended topical treatment for all CLE subtypes. The most relevant factors for initiation of systemic therapy were severity of skin lesions, concomitant involvement of internal organs, CLE subtype and lack of response to topical therapies. Corticosteroids and antimalarials were considered as the most suitable and effective systemic drugs for CLE patients. However, significant differences were observed between various CLE subtypes and between different countries regarding the assessment of various topical and systemic treatment options. In conclusion, great variability of obtained answers underlines the need of development of CLE treatment guidelines suitable for different disease subtypes. PMID- 26821964 TI - Drugs used in incident systemic lupus erythematosus - results from the Finnish nationwide register 2000-2007. AB - The objectives of the study were to examine the initial, first-year anti rheumatic outpatient therapy in patients with incident SLE, as well as the concomitant use of drugs for certain comorbidities, compared to the use in the general population. The Finnish nationwide register data on special reimbursements for medication costs was screened to identify the inception cohort of 566 adult SLE patients (87% females, mean age 46.5 +/- 15.9 years) over the years 2000-2007. The patients were linked to the national Drug Purchase Register. Of those, 90% had purchased at least once some disease-modifying anti-rheumatic drugs (DMARDs) during the first year. Hydroxychloroquine was the most common (76%), followed by azathioprine (15%) and methotrexate (13%). With the exception of increase in mycophenolate mofetil, the proportions remained stable over the whole study period 2000-2007. Drugs for cardiovascular diseases, dyslipidemia, diabetes mellitus, hypothyroidism and obstructive pulmonary disease were more frequently purchased than in the sex- and age-adjusted population, with rate ratios ranging from 1.6 to 7.8. Over the years 2000-2007, almost all the patients with incident SLE in Finland started with a DMARD. Higher percentages of SLE patients were on medication for several common chronic diseases than in the population as a whole. PMID- 26821965 TI - The chronic damage in systemic lupus erythematosus is driven by flares, glucocorticoids and antiphospholipid antibodies: results from a monocentric cohort. AB - OBJECTIVES: Literature data suggest a significantly higher mortality in patients affected by systemic lupus erythematosus (SLE) developing chronic damage. Therefore, damage prevention is a major goal in the management of SLE patients. In the present study, we assessed damage by means of the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI), in a large cohort of SLE patients. Additionally, we aimed at evaluating its association with demographic and clinical features as well as with disease activity and laboratory findings. PATIENTS AND METHODS: We enrolled consecutive patients affected by SLE diagnosed according to the American College of Rheumatology (ACR) 1997 revised criteria. Chronic damage was determined by SDI calculated at the last examination in all patients with at least six months of follow-up. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K); flare was defined as an increase of SLEDAI-2K >= 4 compared with the previous visit. RESULTS: We evaluated 349 SLE patients (M/F 25/324, mean age +/- SD 42.7 +/- 12.4 years, mean disease duration +/- SD 164.9 +/- 105.2 months). Among the enrolled patients, 125 (35.8%) showed a SDI >= 1 (mean SDI +/- SD 1.7 +/- 0.9, range 0-5). The musculo-skeletal was the most frequently involved organ/system in SDI score (41/349 patients, 11.7%), with deforming/erosive arthritis in 21/349 (6.0%). The presence of chronic damage was associated with age (P < 0.001), disease duration (P < 0.001), number of flares (P = 0.02) and with the use of glucocorticoids (P = 0.02). The logistic regression analysis revealed the association between neuropsychiatric damage and antiphospholipid syndrome (P = 0.01, OR = 3.9) and between the presence of cardiovascular damage and anti-beta2GPI antibodies (P = 0.01, OR 6.2). CONCLUSIONS: In the present study chronic damage was identified in about one third of SLE patients. The association between SDI and the number of flares claim for a thigh-control of the disease activity in order to prevent the chronic damage. The possible role of antiphospholipid antibodies (aPL) in the development of neuropsychiatric and cardiovascular damage may suggest a more careful assessment of such aPL positive patients. PMID- 26821966 TI - Herpes zoster infection in childhood-onset systemic lupus erythematosus patients: a large multicenter study. AB - OBJECTIVE: The aim of this multicenter study in a large childhood-onset systemic lupus erythematosus (cSLE) population was to assess the herpes zoster infection (HZI) prevalence, demographic data, clinical manifestations, laboratory findings, treatment, and outcome. METHODS: A retrospective multicenter cohort study (Brazilian cSLE group) was performed in ten Pediatric Rheumatology services in Sao Paulo State, Brazil, and included 852 cSLE patients. HZI was defined according to the presence of acute vesicular-bullous lesions on erythematous/edematous base, in a dermatomal distribution. Post-herpetic neuralgia was defined as persistent pain after one month of resolution of lesions in the same dermatome. Patients were divided in two groups for the assessment of current lupus manifestations, laboratory findings, and treatment: patients with HZI (evaluated at the first HZI) and patients without HZI (evaluated at the last visit). RESULTS: The frequency of HZI in cSLE patients was 120/852 (14%). Hospitalization occurred in 73 (61%) and overlap bacterial infection in 16 (13%). Intravenous or oral aciclovir was administered in 113/120 (94%) cSLE patients at HZI diagnosis. None of them had ophthalmic complication or death. Post-herpetic neuralgia occurred in 6/120 (5%). After Holm-Bonferroni correction for multiple comparisons, disease duration (1.58 vs 4.41 years, p < 0.0001) was significantly lower in HZI cSLE patients compared to those without HZI. Nephritis (37% vs 18%, p < 0.0001), lymphopenia (32% vs 17%, p < 0.0001) prednisone (97% vs 77%, p < 0.0001), cyclophosphamide (20% vs 5%, p < 0.0001) and SLE Disease Activity Index 2000 (6.0 (0-35) vs 2 (0-45), p < 0.0001) were significantly higher in the former group. The logistic regression model showed that four independent variables were associated with HZI: disease duration < 1 year (OR 2.893 (CI 1.821-4.597), p < 0.0001), lymphopenia <1500/mm(3) (OR 1.931 (CI 1.183-3.153), p = 0.009), prednisone (OR 6.723 (CI 2.072-21.815), p = 0.002), and cyclophosphamide use (OR 4.060 (CI 2.174-7.583), p < 0.0001). CONCLUSION: HZI is an early viral infection in cSLE with a typical dermatomal distribution. Lymphopenia and immunosuppressive treatment seem to be major factors underlying this complication in spite of a benign course. PMID- 26821967 TI - Risk of psychiatric disorders following pelvic inflammatory disease: a nationwide population-based retrospective cohort study. AB - Pelvic inflammatory disease (PID) a common infection in women that is associated with significant morbidity and is a major cause of infertility. A clear temporal causal relationship between PID and psychiatric disorders has not been well established. We used a nationwide population-based retrospective cohort study to explore the relationship between PID and the subsequent development of psychiatric disorders. We identified subjects who were newly diagnosed with PID between 1 January 2000 and 31 December 2002 in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed for patients without PID. A total of 21 930 PID and 21 930 matched control patients were observed until diagnosed with psychiatric disorders, or until death, withdrawal from the NHI system, or until 31 December 2009. Adjusted hazard ratio (HR) of bipolar disorder, depressive disorder, anxiety disorder and sleep disorder in subjects with PID were significantly higher (HR: 2.671, 2.173, 2.006 and 2.251, respectively) than that of the controls during the follow-up. PID may increase the risk of subsequent newly diagnosed bipolar disorder, depressive disorder, anxiety disorder and sleep disorder, which will impair life quality. Our findings highlight that clinicians should pay particular attention to psychiatric comorbidities in PID patients. PMID- 26821968 TI - The experience of perimenopausal distress: examining the role of anxiety and anxiety sensitivity. AB - OBJECTIVE: The hormonal changes that occur in perimenopause can result in distress for a significant proportion of women years before reaching menopause. Previous studies have suggested that various biopsychosocial characteristics and personality traits contribute to more intense reactions to these hormonal changes. In the present study, we examined the contribution of trait anxiety and anxiety sensitivity in predicting the experience of perimenopausal distress in pre- and early perimenopausal women while controlling for some menstrual experiences. METHOD: A sample of 660 women aged 35-52 years was selected from a broader online survey of biopsychosocial changes in middle-aged women that considered age, menstrual cycle pattern, physical and mental health, and childbearing experience. Three hierarchical multiple regression analyses were conducted for different age subgroups: women aged 35-40, women aged 41-45 and women aged 46-52. RESULTS: Results indicated that anxiety and anxiety sensitivity, along with a number of features of the menstrual experience, explained 56-66% of the perimenopausal distress variance. Different personality trait predictors were found to be important in different age subgroups. In the youngest and middle subgroups (45 years and younger), trait anxiety was found to be more significant, whereas anxiety sensitivity was found to be more important in explaining perimenopausal distress experienced by women older than 40. CONCLUSION: Anxiety sensitivity (dimension of psychological concerns) might be an important vulnerability factor in the experience of perimenopausal distress among women closer to menopause, whereas the predisposition to an anxiety response might contribute to perimenopausal distress near the beginning of reproductive hormonal changes. Implications for better understanding the development of perimenopausal distress and psychological intervention are discussed. PMID- 26821971 TI - Transformation: A New Kind of Academic Health Center and the Pursuit of High Self Mastery. PMID- 26821972 TI - Patterns of Failure of a Standardized Perioperative Venous Thromboembolism Prophylaxis Protocol. AB - BACKGROUND: Venous thromboembolism (VTE) is a leading contributor to morbidity after operations. We previously implemented a standardized VTE risk assessment, based on the Caprini score, along with risk-stratified prophylaxis. This system reduced the odds ratio of a VTE event from 3.02 to 0.75. We investigated patterns of failure to determine characteristics of patients in whom VTE develops despite the protocol. METHODS: We reviewed all nontrauma general surgery patients with evidence of VTE after the inception of a VTE risk assessment and prophylaxis program. Characteristics were recorded, including demographics, diagnoses, operations, risk profile, prophylaxis prescribed, and regimen compliance. RESULTS: Twenty-seven patients failed the protocol and manifested VTE, representing an overall VTE rate of 0.3%. Of these patients, 63% had emergency operations and 52% underwent multiple operations, compared with 13% and 2.0% of the nontrauma general surgery population in whom VTE did not develop, respectively (p < 0.001). Of patients with VTE, 52% had pre-existing or postoperative infections, 22% had malignancies, but only 15% had missed 1 or more doses of pharmacologic prophylaxis during hospitalization. Five VTEs manifested after discharge; one of those patients was prescribed extended prophylaxis beyond hospitalization, and an extended course was not provided to 3 who were eligible. One patient had underestimation of the Caprini score due to lack of awareness of a family history of VTE. CONCLUSIONS: Emergency and multiple operations seem to confer dramatic hazards for VTE, despite standard prophylaxis. These factors are not currently captured in the Caprini model, but might be significant modifiers of risk that should prompt reassessment, perhaps with a weighted numeric value along with enhanced prophylaxis. It is encouraging that most patients received appropriate prophylaxis in compliance with the protocol. PMID- 26821970 TI - Prognostic Molecular Subtypes of Low-Grade Cancer of the Appendix. AB - BACKGROUND: Appendiceal cancer (AC) patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) often demonstrate an unpredictable variability in their survival outcomes. Biomarkers predictive of CRS/HIPEC efficacy could better guide treatment decisions. We hypothesized that variation in the transcriptional programming of AC tumors might distinguish molecular subtypes with differential outcomes after CRS/HIPEC. STUDY DESIGN: Gene expression profiles of 2 AC cohorts were analyzed using Affymetrix whole-genome expression microarrays. Hierarchical clustering methods, Kaplan-Meier analysis, and Cox regression models were used to discover and validate prognostic molecular subtypes of AC. Gene set enrichment analysis was used to infer pathologic attributes of the molecular subtypes. RESULTS: Unsupervised hierarchical clustering analysis of tumor expression profiles revealed a 139-gene cassette that distinguished 2 molecular subtypes (based on low vs high expression of the gene cassette) with statistically significant survival differences (disease specific survival, p = 0.0075; progression-free survival, p = 0.0072). In a second AC cohort, the 139-gene cassette reproducibly partitioned tumors into subtypes with significant survival differences. Tumors showing high relative expression of the genes comprising the cassette associated with poor survival outcomes (disease-specific survival, p = 0.047; progression-free survival, p = 0.0079), and exhibited gene expression patterns enriched for oncogenic processes and pathways. The prognostic value of the molecular subtypes was specific for low grade appendiceal tumors (disease-specific survival, p = 0.028; progression-free survival, p = 0.0016), and remained significant in the presence of conventional prognostic markers, including grade, surgical resection score, Eastern Cooperative Oncology Group status, and age. CONCLUSIONS: The 139-gene cassette can have actionable clinical utility for identifying low-grade appendiceal tumor molecular subtypes predictive of therapeutic efficacy of CRS/HIPEC. PMID- 26821973 TI - Promoting transparency of research and data needs much more attention. PMID- 26821974 TI - Impact of fetal or child loss on parents' perceptions of non-invasive prenatal diagnosis for autosomal recessive conditions. AB - OBJECTIVE: to explore parents' personal attitudes towards non-invasive prenatal diagnosis in the context of their own experiences caring for a child affected with a genetic condition or after the loss of a fetus, infant, or child due to the condition. METHODS: we collected in-depth data from parents via either focus groups or individual interviews. DESIGN: this was a cross-sectional interpretive study based on grounded theory. SETTING: United Kingdom. PARTICIPANTS: 17 parents (13 women and four men) who were carriers of a serious autosomal recessive condition: spinal muscular atrophy, cystic fibrosis or thalassaemia. All had a child (living or deceased) with the condition. FINDINGS: parents experienced changes in reproductive self-identity due to their experiences of having an affected child: this influenced their views of non-invasive prenatal testing. They began their reproductive journeys 'naively', but described feelings of reproductive vulnerability after the diagnosis of the child and consequent realisation of risks to future children. They viewed non-invasive prenatal testing as a way to reduce threats to unborn children, while allowing prenatal diagnosis. KEY CONCLUSIONS: when parents lose a child they may use emotional guarding, delayed pregnancy disclosure and avoidance of harmful activities to cope in future pregnancies. Parents who want to consider early prenatal testing are less able to utilise these strategies, but non-invasive methods allow them to reduce the risk. IMPLICATIONS FOR PRACTICE: midwives should be sensitive to parents' reproductive vulnerability after genetic diagnosis of a child and ensure they are supported to consider the option of non-invasive prenatal testing if appropriate. PMID- 26821975 TI - Antenatal management of gestational diabetes mellitus can improve neonatal outcomes. AB - OBJECTIVE: Pregnancies complicated with gestational diabetes mellitus (GDM) are at a higher risk for caesarean and instrumental deliveries as well as adverse neonatal outcomes such as fetal overgrowth, hypoglycaemia and neonatal intensive care admission. Our primary objective was to describe neonatal outcomes in a sample that included term infants of both GDM mothers and mothers with normal glucose tolerance (NGT). DESIGN AND SETTING: this cross-sectional study included 599 term babies born between September and October 2010 at Royal Prince Alfred Hospital, Sydney, Australia. Maternal and neonatal data were collected from medical records and a questionnaire. Glycaemic control data was based on third trimester HbA1c levels and self-monitoring blood glucose levels (BGL). Univariate associations between GDM status and maternal demographic factors, as well as pregnancy outcomes, were estimated using chi(2) tests and t-tests, as appropriate. FINDINGS: of 599 babies, 67(11%) were born to GDM mothers. GDM mothers were more likely to be overweight/obese and of Asian ethnicity. Good glycaemic control was achieved in most GDM mothers. GDM babies were more likely to have been induced (p=0.013) and delivered earlier than non-GDM mothers (p<0.001), and they were also more likely to be breastfed within one hour of birth. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: in this study, GDM infants were more likely to be induced and delivered earlier but otherwise they did not have significantly different neonatal outcomes compared to infants of NGT mothers. This can be attributed to the good GDM control by lifestyle modification and insulin if necessary. The role of labour induction in GDM pregnancies should be further investigated. Midwives have an important role in maternal education during pregnancy and in the postnatal period. PMID- 26821977 TI - BDNF Val66Met genotype determines hippocampus-dependent behavior via sensitivity to glucocorticoid signaling. PMID- 26821976 TI - Protein cofactor competition regulates the action of a multifunctional RNA helicase in different pathways. AB - A rapidly increasing number of RNA helicases are implicated in several distinct cellular processes, however, the modes of regulation of multifunctional RNA helicases and their recruitment to different target complexes have remained unknown. Here, we show that the distribution of the multifunctional DEAH-box RNA helicase Prp43 between its diverse cellular functions can be regulated by the interplay of its G-patch protein cofactors. We identify the orphan G-patch protein Cmg1 (YLR271W) as a novel cofactor of Prp43 and show that it stimulates the RNA binding and ATPase activity of the helicase. Interestingly, Cmg1 localizes to the cytoplasm and to the intermembrane space of mitochondria and its overexpression promotes apoptosis. Furthermore, our data reveal that different G patch protein cofactors compete for interaction with Prp43. Changes in the expression levels of Prp43-interacting G-patch proteins modulate the cellular localization of Prp43 and G-patch protein overexpression causes accumulation of the helicase in the cytoplasm or nucleoplasm. Overexpression of several G-patch proteins also leads to defects in ribosome biogenesis that are consistent with withdrawal of the helicase from this pathway. Together, these findings suggest that the availability of cofactors and the sequestering of the helicase are means to regulate the activity of multifunctional RNA helicases and their distribution between different cellular processes. PMID- 26821978 TI - Glutamatergic mechanisms of comorbidity between acute stress and cocaine self administration. AB - There is substantial comorbidity between stress disorders and substance use disorders (SUDs), and acute stress augments the locomotor stimulant effect of cocaine in animal models. Here we endeavor to understand the neural underpinnings of comorbid stress disorders and drug use by determining whether the glutamatergic neuroadaptations that characterize cocaine self-administration are induced by acute stress. Rats were exposed to acute (2 h) immobilization stress, and 3 weeks later the nucleus accumbens core was examined for changes in glutamate transport, glutamate-mediated synaptic currents and dendritic spine morphology. We also determined whether acute stress potentiated the acquisition of cocaine self-administration. Acute stress produced an enduring reduction in glutamate transport and potentiated excitatory synapses on medium spiny neurons. Acute stress also augmented the acquisition of cocaine self-administration. Importantly, by restoring glutamate transport in the accumbens core with ceftriaxone the capacity of acute stress to augment the acquisition of cocaine self-administration was abolished. Similarly, ceftriaxone treatment prevented stress-induced potentiation of cocaine-induced locomotor activity. However, ceftriaxone did not reverse stress-induced synaptic potentiation, indicating that this effect of stress exposure did not underpin the increased acquisition of cocaine self-administration. Reversing acute stress-induced vulnerability to self administer cocaine by normalizing glutamate transport poses a novel treatment possibility for reducing comorbid SUDs in stress disorders. PMID- 26821980 TI - Determination of Chondroitin Sulfate Content in Raw Materials and Dietary Supplements by High-Performance Liquid Chromatography with UV Detection After Enzymatic Hydrolysis: Single-Laboratory Validation First Action 2015.11. AB - A previously validated method for determination of chondroitin sulfate in raw materials and dietary supplements was submitted to the AOAC Expert Review Panel (ERP) for Stakeholder Panel on Dietary Supplements Set 1 Ingredients (Anthocyanins, Chondroitin, and PDE5 Inhibitors) for consideration of First Action Official Methods(SM) status. The ERP evaluated the single-laboratory validation results against AOAC Standard Method Performance Requirements 2014.009. With recoveries of 100.8-101.6% in raw materials and 105.4-105.8% in finished products and precision of 0.25-1.8% RSDr within-day and 1.6-4.72% RSDr overall, the ERP adopted the method for First Action Official Methods status and provided recommendations for achieving Final Action status. PMID- 26821979 TI - Contribution of non-genetic factors to dopamine and serotonin receptor availability in the adult human brain. AB - The dopamine (DA) and serotonin (5-HT) neurotransmission systems are of fundamental importance for normal brain function and serve as targets for treatment of major neuropsychiatric disorders. Despite central interest for these neurotransmission systems in psychiatry research, little is known about the regulation of receptor and transporter density levels. This lack of knowledge obscures interpretation of differences in protein availability reported in psychiatric patients. In this study, we used positron emission tomography (PET) in a twin design to estimate the relative contribution of genetic and environmental factors, respectively, on dopaminergic and serotonergic markers in the living human brain. Eleven monozygotic and 10 dizygotic healthy male twin pairs were examined with PET and [(11)C]raclopride binding to the D2- and D3 dopamine receptor and [(11)C]WAY100635 binding to the serotonin 5-HT1A receptor. Heritability, shared environmental effects and individual-specific non-shared effects were estimated for regional D2/3 and 5-HT1A receptor availability in projection areas. We found a major contribution of genetic factors (0.67) on individual variability in striatal D2/3 receptor binding and a major contribution of environmental factors (pairwise shared and unique individual; 0.70-0.75) on neocortical 5-HT1A receptor binding. Our findings indicate that individual variation in neuroreceptor availability in the adult brain is the end point of a nature-nurture interplay, and call for increased efforts to identify not only the genetic but also the environmental factors that influence neurotransmission in health and disease. PMID- 26821981 TI - Genome-wide association analysis to predict optimal antipsychotic dosage in schizophrenia: a pilot study. AB - In recent years, several studies have investigated genetic polymorphisms of antipsychotic drug-metabolizing enzymes and receptors. However, most studies focused on drug response and very few have investigated the genetic influence on antipsychotic dosage. The aim of the present study is to test the association between antipsychotic dosages at genome-wide level. The current dosage of antipsychotic medications was collected from 79 schizophrenia patients. The dosage was standardized using three different methods: chlorpromazine equivalent (CPZe), defined daily dose (DDD), and percentage of maximum dose (PM %). The patients were then genotyped using the Illumina HumanOmni2.5-8 BeadChip Kit. All markers were screened for significance using linear regression, and the p values were visualized using a Manhattan plot. The genome-wide analysis showed that the top Single-Nucleotide Polymorphisms (SNPs) associated with dosage variation were rs981975 on chromosome 14 for CPZe, rs4470690 on chromosome 4 for PM %, and rs79323383 on chromosome 8 for DDD. However, no genome-wide significantly associated SNPs were identified. In this pilot sample, we found promising trends for pharmacodynamic targets associated with antipsychotic dosage. Therefore, studies combining large prescription databases may identify genetic predictors to adjust the dose of antipsychotic medication. PMID- 26821982 TI - Predictability of depression severity based on posterior alpha oscillations. AB - OBJECTIVE: We aimed to integrate neural data and an advanced machine learning technique to predict individual major depressive disorder (MDD) patient severity. METHODS: MEG data was acquired from 22 MDD patients and 22 healthy controls (HC) resting awake with eyes closed. Individual power spectra were calculated by a Fourier transform. Sources were reconstructed via beamforming technique. Bayesian linear regression was applied to predict depression severity based on the spatial distribution of oscillatory power. RESULTS: In MDD patients, decreased theta (4-8 Hz) and alpha (8-14 Hz) power was observed in fronto-central and posterior areas respectively, whereas increased beta (14-30 Hz) power was observed in fronto central regions. In particular, posterior alpha power was negatively related to depression severity. The Bayesian linear regression model showed significant depression severity prediction performance based on the spatial distribution of both alpha (r=0.68, p=0.0005) and beta power (r=0.56, p=0.007) respectively. CONCLUSIONS: Our findings point to a specific alteration of oscillatory brain activity in MDD patients during rest as characterized from MEG data in terms of spectral and spatial distribution. SIGNIFICANCE: The proposed model yielded a quantitative and objective estimation for the depression severity, which in turn has a potential for diagnosis and monitoring of the recovery process. PMID- 26821984 TI - Platinum-based heterogeneous nanomaterials via wet-chemistry approaches toward electrocatalytic applications. AB - The heterogeneously structured nanomaterials usually exhibit enhanced catalytic properties in comparison with each one of the constituent materials due to the synergistic effect among their different domains. Within the last decade, the development of wet-chemistry methods leads to the blossom of research in materials with heterogeneous nanostructures, which creates great opportunities also a tremendous challenge to apply these materials for highly efficient energy conversion. We herein would systematically introduce the latest research developments in Pt-based nanomaterials with heterogeneous structures, e.g. core shell, hollow interiors, stellated/dendritic morphologies, dimeric, or composite construction, and their potential applications as electrocatalysts toward direct methanol fuel cell reactions, including methanol oxidation reaction and oxygen reduction reaction in acidic conditions, aiming at the summarization of the fundamentals and technical approaches in synthesis, fabrication and processing of heterogeneous nanomaterials so as to provide the readers a systematic and coherent picture of the filed. This review will focus on the intrinsic relationship between the catalytic properties and the physical or/and chemical effects in the heterogeneous nanomaterials, providing for technical bases for effectively developing novel electrocatalyts with low cost, enhanced activity and high selectivity. PMID- 26821983 TI - First-generation HapMap in Cajanus spp. reveals untapped variations in parental lines of mapping populations. AB - Whole genome re-sequencing (WGRS) was conducted on a panel of 20 Cajanus spp. accessions (crossing parentals of recombinant inbred lines, introgression lines, multiparent advanced generation intercross and nested association mapping population) comprising of two wild species and 18 cultivated species accessions. A total of 791.77 million paired-end reads were generated with an effective mapping depth of ~12X per accession. Analysis of WGRS data provided 5 465 676 genome-wide variations including 4 686 422 SNPs and 779 254 InDels across the accessions. Large structural variations in the form of copy number variations (2598) and presence and absence variations (970) were also identified. Additionally, 2 630 904 accession-specific variations comprising of 2 278 571 SNPs (86.6%), 166 243 deletions (6.3%) and 186 090 insertions (7.1%) were also reported. Identified polymorphic sites in this study provide the first-generation HapMap in Cajanus spp. which will be useful in mapping the genomic regions responsible for important traits. PMID- 26821985 TI - Recurrent Coxsackievirus Infection in a Patient with Lamellar Ichthyosis. AB - We describe a case of coxsackievirus (CV) A6 infection in a patient with lamellar ichthyosis followed by subsequent CV A8 infection within the same year. Atypical cutaneous features characterized the infection. This observation, combined with the rapidity with which reinfection occurred, suggests that the natural history of CV infection may be altered in patients with underlying ichthyoses. PMID- 26821986 TI - A Palladium-Catalyzed Carbonylation Approach to Eight-Membered Lactam Derivatives with Antitumor Activity. AB - The reactivity of 2-(2-alkynylphenoxy)anilines under PdI2 /KI-catalyzed oxidative carbonylation conditions has been studied. Although a different reaction pathway could have been operating, N-palladation followed by CO insertion was the favored pathway with all substrates tested, including those containing an internal or terminal triple bond. This led to the formation of a carbamoylpalladium species, the fate of which, as predicted by theoretical calculations, strongly depended on the nature of the substituent on the triple bond. In particular, 8-endo-dig cyclization preferentially occurred when the triple bond was terminal, leading to the formation of carbonylated zeta-lactam derivatives, the structures of which have been confirmed by XRD analysis. These novel medium-sized heterocyclic compounds showed antitumor activity against both estrogen receptor-positive (MCF 7) and triple negative (MDA-MB-231) breast cancer cell lines. In particular, zeta lactam 3 j' may represent a novel and promising antitumor agent because biological tests clearly demonstrate that this compound significantly reduces cell viability and motility in both MCF-7 and MDA-MB-231 breast cancer cell lines, without affecting normal breast epithelial cell viability. PMID- 26821987 TI - Impact of the lower third molar and injury mechanism on the risk of mandibular angle and condylar fractures. AB - BACKGROUND: Previous studies have shown the influence of the mandibular third molar on mandibular angle and condylar fractures, but have not comparatively analyzed the impact of the injury mechanism on these fractures. The purpose of this study was to evaluate the influence of the lower third molar (M3) and injury related factors (fracture etiology and site of impact of the traumatic force) on the risk of mandibular angle and condylar fractures. MATERIAL AND METHODS: The study included 615 patients who sustained a mandibular fracture in a 13-year period (from January 2000 to December 2013). The independent variables were presence, position and the root number of the M3, fracture etiology, and site of impact of the force. The outcome variables were mandibular angle and condylar fractures. Other variables included in the study were patients' gender and age. The data were analyzed using the chi-square test. Univariate and multivariate binary logistic regression analyses were used to evaluate the relationship between angle and condylar fractures and to show potential determinants. RESULTS: Angle fractures were significantly influenced by the M3, site of impact, and age, but the main predictors were the eruption status and vertical position of the M3 (classified by Pell and Gregory) and site of impact of the force. Condylar fractures were significantly influenced by the M3 and site of impact of the force, but only the last showed as a predictor. CONCLUSIONS: Factors related to the M3 showed more significant influence on angle fractures than on condylar fractures. PMID- 26821988 TI - Multivariate Familial Analysis of Cognitive Measures in the Colorado Family Reading Study. AB - Multivariate path analysis is employed to examine the etiologies of variation and covariation of three composite cognitive measures in the Colorado Family Reading Study: reading ability, symbol-processing speed, and spatial/reasoning. Measures of phenotypic assortative and cross-assortative mating are incorporated in a multivariate analysis of familial resemblance within nuclear families. Phenotypic variances and covariances are partitioned into components due to familial (genetic and/or family environmental) influences and to specific, nontransmissible environmental influences in families with a reading-disabled child as well as families with children of normal reading ability. Comparable moderate familial influences are found across family type for all three composites and the phenotypic correlations between traits are largely due to familial influences. PMID- 26821989 TI - Implicit Theories of Personality: Further Evidence of Extreme Response Style. AB - Five groups of 19 subjects made ratings on 11 personality trait scales of overlapping subsets of 59 artificial stimulus persons who were described by one to five personality trait adjectives. The data were analyzed per group of subjects (blockwise) and per type of stimulus person (questionnaire-wise) by means of three-mode principal component analyses. This yielded highly similar structures for the scales, and in the blockwise analyses, for the stimulus persons. This similarity was substantiated by external three-mode analyses, which showed that all stimulus persons can be mapped into one overall configuration. In all analyses it was found that differences between subjects consisted of differences in extremity of judgment, which suggests the operation of response style. PMID- 26821990 TI - Multitrait-Multimethod Comparisons Across Populations: A Confirmatory Factor Analytic Approach. AB - The advantages of multitrait-multimethod (MTMM) methodology and the power of maximum likelihood confirmatory factor analysis are combined in an ordered framework for the comparison of covariance structures and true means across populations. First, a sequence of tests of and between hierarchically nested confirmatory factor analytic models is described for the analysis of measurement equivalence and construct validity across populations. Second, a similar sequence of model comparisons is proposed for the detection of true score-observed score regression intercept differences and true mean differences between populations. The proposed procedure is contrasted with MANOVA comparisons of group means: (1) use of MANOVA assumes test equivalence and validity across populations, whereas the present procedure permits statistical analysis of these assumptions; (2) MANOVA bases discriminant function coefficients partially upon observed differences between groups, whereas the current procedure weights each variate according to its correlation with an underlying construct. The possibility of spurious results from MANOVA and verdical results from the proposed methodology is demonstrated via application of both procedures to an artificial data set. PMID- 26821991 TI - Personality Factor Structure in Psychiatric Outpatients and Normals. AB - The Comrey Personality Scales (CPS) were administered to 394 psychiatric outpatients. The 40 subscales that define the eight CPS factors were intercorrelated and factor analyzed to determine if the same structure of personality traits fits beth normal and psychologically disturbed individuals. The factor structure in this study was very close to that found previously in six other widely different kinds of populations. These results support a previously stated conclusion that tests of normal personality traits are appropriate for use in assessment with psychologically disturbed individuals. PMID- 26821992 TI - The Structure of Masculinity/Femininity: An Application of Confirmatory Factor Analysis to Higher-Order Factor Structures and Factorial Invariance. AB - The purpose of this study is to examine the factor structure of responses to the masculinity/femininity (MF) scale of the Comrey Personality Scales for males (N = 366) and females (N = 384). The study also illustrates the use of confirmatory factor analysis for testing hierarchical factor structures and factorial invariance. The MF scale consists of M and F items designed to measure five distinguishable components of MF. Neither a one-factor solution with a single bipolar MF factor, nor a two-factor solution with separate M and F factors, was able to fit the data. However, a five-factor solution derived from the design of the MF scale provided an adequate fit, and the relationships among the five first order factors could be explained by a single higher-order, bipolar MF factor. Contrary to the findings and proposals from androgyny research, when separate masculinity and femininity constructs were defined, the correlation between the constructs was nearly - 1.0. The findings argue that MF is a multifaceted, hierarchical construct instead of either a single bipolar MF construct, or separate M and F factors. PMID- 26821993 TI - Hierarchical Models of Attitude. AB - Although the philosophy of science literature argues that a distinction should be made between different levels of abstraction, it is only recently that such models have been developed and estimated by researchers in the social sciences. Estimation of such hierarchical models, which was not possible earlier, is made easier by the work of Bentler and Weeks (1979) and Joreskog and Sorbom (1981). This paper illustrates the application and use of hierarchical models using the structure of attitude as an example. Hierarchical models of attitude showed considerably better fit and interpretable results than the non-hierarchical model. Such models also appear to be a better way to conceptualize and estimate models in the presence of collinear constructs. Caution should be exercised, however, as higher-order models may not be uniquely determined. PMID- 26821994 TI - Extending the g.c.r. Tables: n < 1 and n > 1000. AB - Meaningful critical values of the greatest characteristic root (g.c.r.) distribution exist for n = 0 and for n = -.5. Formulas and tables to aid in determining g.c.r, critical values for those cases and for n > 1000 are provided. PMID- 26821995 TI - Postoperative chemoradiotherapy versus radiotherapy alone for cervical cancer: A systematic review and meta-analysis. AB - The aim of this study was to compare the treatment outcomes of postoperative chemoradiotherapy (CRT) with radiotherapy (RT) alone in patients with cervical cancer. Based on articles published up to December 2014 a literature search in PubMed and EMBASE was conducted to identify eligible studies. Risk ratio (RR) and its 95% confidence interval (CI) were used as pooled statistics. A total of 4 articles consisting of 461 patients were selected for the meta-analysis. Results revealed that there were a significant overall survival improvements (RR = 1.35, 95% CI: 1.15-1.60, p = 0.0003), a significant reduction of local recurrence (RR = 0.26, 95% CI: 0.14-0.51, p < 0001) and distant recurrence (RR = 0.41, 95% CI: 0.26-0.63, p < 0.0001) in the patients who received postoperative CRT, comparing with the patients who received RT alone. In conclusion, the results suggest a significant benefit of CRT for patients with cervical cancer, comparing with RT alone treatment. PMID- 26821996 TI - RNA-binding protein hnRNPLL as a critical regulator of lymphocyte homeostasis and differentiation. AB - RNA-binding proteins orchestrate posttranscriptional regulation of gene expression, such as messenger RNA (mRNA) splicing, RNA stability regulation, and translation regulation. Heterogeneous nuclear RNA-binding proteins (hnRNPs) refer to a collection of unrelated RNA-binding proteins predominantly located in the nucleus (Han et al. Biochem J 2010, 430:379-392). Although canonical functions of hnRNPs are to promote pre-mRNA splicing, they are involved in all the processes of RNA metabolism through recognizing specific cis-elements on RNA (Dreyfuss et al. Annu Rev Biochem 1993, 62:289-321; Huelga et al. Cell Rep 2012, 1:167-178; Krecic and Swanson. Curr Opin Cell Biol 1999, 11:363-371). Heterogeneous nuclear RNA-binding protein L like (hnRNPLL) is a tissue-specific hnRNP, which was identified as a regulator of CD45RA to CD45RO switching during memory T-cell development (Oberdoerffer et al. Science 2008, 321:686-691; Topp et al. RNA 2008, 14:2038-2049; Wu et al. Immunity 2008, 29:863-875). Since then, hnRNPLL has emerged as a critical regulator of lymphocyte homeostasis and terminal differentiation, controlling alternative splicing or expression of critical genes for the lymphocytes development (Wu et al. Immunity 2008, 29:863-875; Chang et al. Proc Natl Acad Sci USA 2015, 112:E1888-E1897). This review will summarize recent advances in understanding the functions of hnRNPLL, focusing on its biochemical functions and physiological roles in lymphocyte differentiation and homeostasis. WIREs RNA 2016, 7:295-302. doi: 10.1002/wrna.1335 For further resources related to this article, please visit the WIREs website. PMID- 26821997 TI - Superstable Magnetic Nanoparticles in Conjugation with Near-Infrared Dye as a Multimodal Theranostic Platform. AB - Near-infrared (NIR) dyes functionalized magnetic nanoparticles (MNPs) have been widely applied in magnetic resonance imaging (MRI), NIR fluorescence imaging, drug delivery, and magnetic hyperthermia. However, the stability of MNPs and NIR dyes in water is a key problem to be solved for long-term application. In this study, a kind of superstable iron oxide nanoparticles was synthesized by a facile way, which can be used as T1 and T2 weighted MRI contrast agent. IR820 was grafted onto the surface of nanoparticles by 6-amino hexanoic acid to form IR820 CSQ-Fe conjugates. Attached IR820 showed increased stability in water at least for three months and an enhanced ability of singlet oxygen production of almost double that of free dyes, which will improve its efficiency for photodynamic therapy. Meanwhile, the multispectral optoacoustic tomography (MSOT) and NIR imaging ability of IR820-CSQ-Fe will greatly increase the accuracy of disease detection. All of these features will broaden the application of this material as a multimodal theranostic platform. PMID- 26821998 TI - Giant Amplification of Photoswitching by a Few Photons in Fluorescent Photochromic Organic Nanoparticles. AB - Controlling or switching the optical signal from a large collection of molecules with the minimum of photons represents an extremely attractive concept. Promising fundamental and practical applications may be derived from such a photon-saving principle. With this aim in mind, we have prepared fluorescent photochromic organic nanoparticles (NPs), showing bright red emission, complete ON-OFF contrast with full reversibility, and excellent fatigue resistance. Most interestingly, upon successive UV and visible light irradiation, the NPs exhibit a complete fluorescence quenching and recovery at very low photochromic conversion levels (<5 %), leading to the fluorescence photoswitching of 420+/-20 molecules for only one converted photochromic molecule. This "giant amplification of fluorescence photoswitching" originates from efficient intermolecular energy transfer processes within the NPs. PMID- 26821999 TI - A Systematic Framework and Nanoperiodic Concept for Unifying Nanoscience: Hard/Soft Nanoelements, Superatoms, Meta-Atoms, New Emerging Properties, Periodic Property Patterns, and Predictive Mendeleev-like Nanoperiodic Tables. AB - Development of a central paradigm is undoubtedly the single most influential force responsible for advancing Dalton's 19th century atomic/molecular chemistry concepts to the current maturity enjoyed by traditional chemistry. A similar central dogma for guiding and unifying nanoscience has been missing. This review traces the origins, evolution, and current status of such a critical nanoperiodic concept/framework for defining and unifying nanoscience. Based on parallel efforts and a mutual consensus now shared by both chemists and physicists, a nanoperiodic/systematic framework concept has emerged. This concept is based on the well-documented existence of discrete, nanoscale collections of traditional inorganic/organic atoms referred to as hard and soft superatoms (i.e., nanoelement categories). These nanometric entities are widely recognized to exhibit nanoscale atom mimicry features reminiscent of traditional picoscale atoms. All unique superatom/nanoelement physicochemical features are derived from quantized structural control defined by six critical nanoscale design parameters (CNDPs), namely, size, shape, surface chemistry, flexibility/rigidity, architecture, and elemental composition. These CNDPs determine all intrinsic superatom properties, their combining behavior to form stoichiometric nanocompounds/assemblies as well as to exhibit nanoperiodic properties leading to new nanoperiodic rules and predictive Mendeleev-like nanoperiodic tables, and they portend possible extension of these principles to larger quantized building blocks including meta-atoms. PMID- 26822000 TI - Education of residential aged care staff regarding sexuality and sexual health in later life. PMID- 26822001 TI - Epidemiological and clinical features of the endomyocardial form of restrictive cardiomyopathy in cats: a review of 41 cases. AB - Examination of our necropsy records for the period 2005 to 2014 yielded 41 cases of the endomyocardial form of restrictive cardiomyopathy among 327 cats with evidence of heart disease, and here, we reviewed their epidemiological and clinical features. The medical data obtained retrospectively included signalment, presenting complaints, findings of physical examination, results of various diagnostic tests, methods of treatment and survival times. Except for one Chinchilla Persian cat, all were domestic short-haired cats. The mean age at death was 7.3 +/- 4.5 years (median, 6 years; range, 4 months to 19 years), and males accounted for 61% (25/41) of the total. Dyspnea was the most common clinical sign, being evident in 83% (35/41) of the cats. Hind limb paresis or paralysis due to aortic thromboembolism was evident in 41% (17/41). Arrhythmias of atrial origin were common. Echocardiography commonly revealed left atrial or biatrial enlargement with severe endocardial thickening of the left ventricle. Most of the affected cats had a poor outcome; the disease duration ranged from 1 to 977 days, and the median survival period was 30 days. PMID- 26822002 TI - Current status and its epidemiological consideration of Fasciola and Eurytrema infections in beef cattle of Japan. AB - To elucidate current status of fasciolosis and eurytremosis in beef cattle of Japan, inspection data of Tokyo Metropolitan Shibaura Slaughterhouse where beef cattle were shipped from all over Japan were analyzed, and questionnaire to farmers was conducted to assess the relationship between recognition of the disease occurrence in one's own farm and attention to the diseases. The occurrence of fasciolosis and eurytremosis in beef cattle gradually decreased from 18.6% to 0.06% and from 0.58% to 0.02% during the period of 1964 to 2010, respectively. When the current data from 2009 to 2012 were analyzed, the occurrence of fasciolosis was recognized in cattle produced and fattened all over Japan, indicating the disease was prevalent nationwide. While, 97.5% of Eurytrema infection were detected in cattle produced in Okinawa, Shimane and Kagoshima, indicating the disease was endemic in these regions. Higher occurrence (>0.7%) of fasciolosis was observed in minor breeds, such as Japanese Shorthorn. Japanese Black showed 0.09% and 0.05% of occurrence for fasciolosis and eurytremosis, respectively, but F1 crossbred with Japanese Black showed lower occurrence (0.007% and 0.002%, respectively). No tendency of occurrence in the age of cattle at slaughter was recognized, indicating the infections may have occurred at the growing and early fattening stage of cattle. The questionnaire survey revealed that farmers experiencing fasciolosis had more knowledge about the disease, however, factors, such as testing parasite infections and use of anti-Fasciola dewormers, were not affected by the recognition of occurrence. PMID- 26822003 TI - Prevalence and predictive factors for renouncing medical care in poor populations of Cayenne, French Guiana. AB - BACKGROUND: Access to health care is a global public problem. In French Guiana, there exists social inequalities which are specially marked amongst immigrants who make up a third of the population. Health care inequalities are prevalent. The objective of this study was to determine factors associated with why health care amongst the poor population of Cayenne was renounced. The study was cross sectional. It focused on knowledge, attitudes, practices and beliefs of the population living in poor neighborhoods of the Cayenne area. METHODS: Populations coming at the Red Cross mobile screening unit in poor urban areas of Cayenne were surveyed from July 2013 to June 2014. Structured questionnaires consisted of 93 questions. Written informed consent was requested at the beginning of the questionnaire. The predictors for renouncing medical care were determined using logistic regression models and tree analysis. RESULTS: Twenty percent of persons had renounced care. Logistic regression showed that renouncement of health care was negatively associated with having no regular physician Adjusted Odds Ratio (AOR) = 0.43 (95 % CI = 0.24-0.79) and positively associated with being embarrassed to ask certain questions AOR = 6.81 (95 % CI = 3.98-11.65) and having been previously refused health care by a doctor AOR = 3.08 (95 % CI = 1.43-6.65). Tree analysis also showed that three of these variables were linked to renouncement, with feeling shy to ask certain questions as the first branching. CONCLUSION: Although most people felt it was easy to see a doctor, one in five had renounced health care. The variables identified by the models suggest vulnerable persons generally had previous negative encounters with the health system and felt unwanted or non eligible for healthcare. Health care mediation and welcoming staff may be simple solutions to the above problems which were underscored in our observations. PMID- 26822004 TI - Organic-inorganic hybrid inverted photodiode with planar heterojunction for achieving low dark current and high detectivity. AB - In this study, the strategy of using an organic-inorganic hybrid planar heterojunction consisting of polymeric semiconductors and inorganic nanocrystals is introduced to realize a high-performance hybrid photodiode (HPD) with low dark current and high detectivity. To prevent undesired charge injection under the reverse bias condition, which is the major dark current source of the photodiode, a well-defined planar heterojunction is strategically constructed via smart solution process techniques. The optimized HPD renders a low dark current of ~10( 5) mA cm(-2) at -5 V and ~10(-6) mA cm(-2) at -1 V, as well as a high detectivity ~10(12) Jones across the entire visible wavelength range. Furthermore, excellent photocurrent stability is demonstrated under continuous light exposure. We believe that the solution-processed planar heterojunction with inverted structure can be an attractive alternative diode structure for fabricating high-performance HPDs, which usually suffer from high dark current issues. PMID- 26822005 TI - Esterase-Sensitive Prodrugs with Tunable Release Rates and Direct Generation of Hydrogen Sulfide. AB - Prodrugs that release hydrogen sulfide upon esterase-mediated cleavage of an ester group followed by lactonization are described herein. By modifying the ester group and thus its susceptibility to esterase, and structural features critical to the lactonization rate, H2 S release rates can be tuned. Such prodrugs directly release hydrogen sulfide without the involvement of perthiol species, which are commonly encountered with existing H2 S donors. Additionally, such prodrugs can easily be conjugated to another non-steroidal anti-inflammatory agent, leading to easy synthesis of hybrid prodrugs. As a biological validation of the H2 S prodrugs, the anti-inflammatory effects of one such prodrug were examined by studying its ability to inhibit LPS-induced TNF-alpha production in RAW 264.7 cells. This type of H2 S prodrugs shows great potential as both research tools and therapeutic agents. PMID- 26822007 TI - Syntheses and Promising Properties of Dense Energetic 5,5'-Dinitramino-3,3'-azo 1,2,4-oxadiazole and Its Salts. AB - A planar energetic molecule with high density, 5,5'-dinitramino-3,3'-azo-1,2,4 oxadiazole (4), was obtained by the nitration of 5,5'-diamino-3,3'-azo-1,2,4 oxadiazole using 100 % nitric acid. In addition, selected nitrogen-rich salts were prepared. Of them, the neutral compound 4 and its hydroxylammonium salt, 6, were further confirmed by single-crystal X-ray diffraction. Physicochemical and energetic properties including density, thermal stability, and sensitivity were investigated. The energetic performance from the calculated heats of formation and experimental densities indicates that many of them have potential applications as energetic materials. PMID- 26822008 TI - Managing and mitigating conflict in healthcare teams: an integrative review. AB - AIM: To review empirical studies examining antecedents (sources, causes, predictors) in the management and mitigation of interpersonal conflict. BACKGROUND: Providing quality care requires positive, collaborative working relationships among healthcare team members. In today's increasingly stress-laden work environments, such relationships can be threatened by interpersonal conflict. Identifying the underlying causes of conflict and choice of conflict management style will help practitioners, leaders and managers build an organizational culture that fosters collegiality and create the best possible environment to engage in effective conflict management. DESIGN: Integrative literature review. DATA SOURCES: CINAHL, MEDLINE, PsycINFO, Proquest ABI/Inform, Cochrane Library and Joanne Briggs Institute Library were searched for empirical studies published between 2002-May 2014. REVIEW METHODS: The review was informed by the approach of Whittemore and Knafl. Findings were extracted, critically examined and grouped into themes. RESULTS: Forty-four papers met the inclusion criteria. Several antecedents influence conflict and choice of conflict management style including individual characteristics, contextual factors and interpersonal conditions. Sources most frequently identified include lack of emotional intelligence, certain personality traits, poor work environment, role ambiguity, lack of support and poor communication. Very few published interventions were found. CONCLUSION: By synthesizing the knowledge and identifying antecedents, this review offers evidence to support recommendations on managing and mitigating conflict. As inevitable as conflict is, it is the responsibility of everyone to increase their own awareness, accountability and active participation in understanding conflict and minimizing it. Future research should investigate the testing of interventions to minimize these antecedents and, subsequently, reduce conflict. PMID- 26822006 TI - The Effect of the Canine ABCB1-1Delta Mutation on Sedation after Intravenous Administration of Acepromazine. AB - BACKGROUND: Dog breeds with the ABCB1-1Delta mutation have substantially truncated nonfunctional P-glycoprotein. Dogs homozygous for this mutation (mut/mut) are susceptible to the toxic adverse effects of ivermectin, loperamide, and vincristine. Anecdotal reports suggested ABCB1 mut/mut dogs showed increased depth and duration of acepromazine sedation. HYPOTHESIS/OBJECTIVES: That ABCB1 mut/mut dogs have increased depth and duration of sedation after acepromazine IV compared to normal dogs (nor/nor). ANIMALS: Twenty-nine rough-coated collies were divided into 3 groups of dogs based on their ABCB1 genotype: 10 mut/mut, 10 mut/nor, and 9 nor/nor. METHODS: Dogs were given 0.04 mg/kg of acepromazine IV. Level of sedation, heart rate, respiratory rate, and blood pressure were recorded for 6 hours after acepromazine administration. Area under the curves (AUCs) of the normalized sedation score results were calculated and compared. RESULTS: The median sedation scores for ABCB1 mut/mut dogs were higher than nor/nor dogs at all time points and were higher in mut/nor dogs for the first 2 hours. These differences were not found to be significant for any individual time point (P > .05). The median sedation score AUC for mut/mut dogs was significantly higher than nor/nor dogs (P = .028), but the AUC for mut/nor dogs was not (P = .45). There were no significant differences between groups for heart rate, respiratory rate, and blood pressure (P > .05). CONCLUSIONS AND CLINICAL IMPORTANCE: In ABCB1 mut/mut dogs acepromazine dose rates should be reduced and careful monitoring performed during sedation. PMID- 26822010 TI - Validation of database search strategies for the epidemiological study of eczema herpeticum. PMID- 26822009 TI - Pressure topography metrics for high-resolution pharyngeal-esophageal manofluorography-a normative study of younger and older adults. AB - BACKGROUND: We aimed to define normative values for novel pressure topography metrics for high-resolution pharyngeal-esophageal manofluorography. The effects of age, gender, and bolus properties were examined. METHODS: Concurrent high resolution manometry (HRM) and videofluoroscopy data were collected from 22 younger (aged 21-40) and 22 older (aged 60-80) healthy subjects. Pressure topography was analyzed by correlating pressure domains with videofluoroscopic events. Nine pressure topography metrics of the pharyngeal and proximal esophageal swallow were extracted; four of these were also compared with previously obtained esophageal HRM studies to assess the effects of catheter diameter. KEY RESULTS: Older individuals exhibited more vigorous contractility in the pharynx than did younger subjects with all bolus types, but the greatest values for both groups were with effortful swallow and on that measure the age groups were similar. Upper esophageal sphincter (UES) intrabolus pressure during sphincter opening was also greater in the older subjects. Some gender differences were observed, particularly related to proximal esophageal contractile vigor. Bolus consistency had no consistent effect. Studies using the larger catheter diameter resulted in significantly greater contractile vigor in the UES and proximal esophagus. CONCLUSIONS & INFERENCES: Older adults exhibited more vigorous pharyngeal contractions than young adults, albeit within a similar range of capacity, perhaps reflecting a compensatory response to other age-related physiological changes. Greater UES intrabolus pressures observed during bolus transit in the older group likely reflect reduced UES compliance with age. Normative data on novel HRM metrics collected in this study can serve as a reference for future clinical studies. PMID- 26822011 TI - Ferrous ion regulated extracellular electron transfer: towards self-suppressed microbial iron(III) oxide reduction. AB - By using an electrochemical strategy, we demonstrated that ferrous ions are capable of decreasing bacterial EET activity in a certain potential range where the conduction-band edge of natural abundant iron(III) oxides is located. It is proposed that ferrous ions enable alteration of the formal potential of outer membrane c-type cytochromes, a crucial protein involved in the EET process. PMID- 26822012 TI - Direct Experimental Evidence for Differing Reactivity Alterations of Minerals following Irradiation: The Case of Calcite and Quartz. AB - Concrete, used in the construction of nuclear power plants (NPPs), may be exposed to radiation emanating from the reactor core. Until recently, concrete has been assumed immune to radiation exposure. Direct evidence acquired on Ar(+)-ion irradiated calcite and quartz indicates, on the contrary, that, such minerals, which constitute aggregates in concrete, may be significantly altered by irradiation. More specifically, while quartz undergoes disordering of its atomic structure resulting in a near complete lack of periodicity, calcite only experiences random rotations, and distortions of its carbonate groups. As a result, irradiated quartz shows a reduction in density of around 15%, and an increase in chemical reactivity, described by its dissolution rate, similar to a glassy silica. Calcite however, shows little change in dissolution rate - although its density noted to reduce by ~9%. These differences are correlated with the nature of bonds in these minerals, i.e., being dominantly ionic or covalent, and the rigidity of the mineral's atomic network that is characterized by the number of topological constraints (nc) that are imposed on the atoms in the network. The outcomes have major implications on the durability of concrete structural elements formed with calcite or quartz bearing aggregates in nuclear power plants. PMID- 26822013 TI - Public Mass Shooters and Firearms: A Cross-National Study of 171 Countries. AB - OBJECTIVE: Model the global distribution of public mass shooters around the world. METHOD: Negative binomial regression is used to test the effects of homicide rates, suicide rates, firearm ownership rates, and several control variables on public mass shooters per country from 1966 to 2012. RESULTS: The global distribution of public mass shooters appears partially attributable to cross-national differences in firearms availability but not associated with cross national homicide or suicide rates. CONCLUSION: The United States and other nations with high firearm ownership rates may be particularly susceptible to future public mass shootings, even if they are relatively peaceful or mentally healthy according to other national indicators. PMID- 26822014 TI - Reconstruction of superficial deltoid ligaments with allograft tendons in medial ankle instability: A technical report. AB - BACKGROUND: Deltoid ligament insufficiency can cause arthritic changes with various symptoms in the ankle joint. However, reconstruction procedures of the medial collateral and deltoid ligaments have drawn less attention than those of the lateral ankle ligaments. Few techniques for reconstructing deltoid ligaments are available, and those that are can be complex. OBJECTIVE: We introduce a new surgical method for reconstructing superficial deltoid ligaments that is simple and straightforward. CONCLUSION: With this method, the tibionavicular and tibiocalcaneal ligaments can be reconstructed efficiently and easily. PMID- 26822015 TI - On the analysis of clonogenic survival data: Statistical alternatives to the linear-quadratic model. AB - BACKGROUND: The most frequently used method to quantitatively describe the response to ionizing irradiation in terms of clonogenic survival is the linear quadratic (LQ) model. In the LQ model, the logarithm of the surviving fraction is regressed linearly on the radiation dose by means of a second-degree polynomial. The ratio of the estimated parameters for the linear and quadratic term, respectively, represents the dose at which both terms have the same weight in the abrogation of clonogenic survival. This ratio is known as the alpha/beta ratio. However, there are plausible scenarios in which the alpha/beta ratio fails to sufficiently reflect differences between dose-response curves, for example when curves with similar alpha/beta ratio but different overall steepness are being compared. In such situations, the interpretation of the LQ model is severely limited. METHODS: Colony formation assays were performed in order to measure the clonogenic survival of nine human pancreatic cancer cell lines and immortalized human pancreatic ductal epithelial cells upon irradiation at 0-10 Gy. The resulting dataset was subjected to LQ regression and non-linear log-logistic regression. Dimensionality reduction of the data was performed by cluster analysis and principal component analysis. RESULTS: Both the LQ model and the non linear log-logistic regression model resulted in accurate approximations of the observed dose-response relationships in the dataset of clonogenic survival. However, in contrast to the LQ model the non-linear regression model allowed the discrimination of curves with different overall steepness but similar alpha/beta ratio and revealed an improved goodness-of-fit. Additionally, the estimated parameters in the non-linear model exhibit a more direct interpretation than the alpha/beta ratio. Dimensionality reduction of clonogenic survival data by means of cluster analysis was shown to be a useful tool for classifying radioresistant and sensitive cell lines. More quantitatively, principal component analysis allowed the extraction of scores of radioresistance, which displayed significant correlations with the estimated parameters of the regression models. CONCLUSIONS: Undoubtedly, LQ regression is a robust method for the analysis of clonogenic survival data. Nevertheless, alternative approaches including non-linear regression and multivariate techniques such as cluster analysis and principal component analysis represent versatile tools for the extraction of parameters and/or scores of the cellular response towards ionizing irradiation with a more intuitive biological interpretation. The latter are highly informative for correlation analyses with other types of data, including functional genomics data that are increasingly being generated. PMID- 26822016 TI - Association of Suicidal Ideation with Job Demands and Job Resources: a Large Cross-Sectional Study of Japanese Workers. AB - PURPOSE: This study aimed to identify the association of suicidal ideation with job demands and job resources among Japanese workers. METHODS: Valid data from questionnaires that were pre-collected from 42,499 workers (34,882 males and 7617 females) were used for multilevel logistic regression analyses. Job demands and job resources were selected as potential predictors of suicidal ideation. Lifestyle variables, support from family and friends, and suffering from depressive or eating disorders were used as covariates. RESULTS: In the employee level, most job demands and job resources had significant associations with the risk of suicidal ideation in both sexes. High coworker support had a significant negative association with the risk of suicidal ideation in the organization level, irrespective of their gender. High physical demands and poor physical environment in the organization-level had significant positive associations with increased risk of suicidal ideation only among females. CONCLUSIONS: The risk of suicidal ideation among Japanese workers is associated with job demands and job resources in the employee-level, and coworker support in the organization-level may be important as well. PMID- 26822017 TI - Flexible and rigid ureteroscopy in outpatient surgery. AB - BACKGROUND: Outpatient surgery is critical to improve health care costs. The aim of the study was to prospectively evaluate the results of outpatient treatment of upper tract urinary stones by rigid or flexible ureteroscopy in a routine care setting. METHODS: A database was created at the creation of the outpatient surgery department. 87 patients underwent 100 ureteroscopic procedures for urinary lithiasis from June 2013 to March 2015. RESULTS: Most of our patients were male with 53 men (sex ratio M/F 1.13), with a mean age of 52.9 +/- 15 years old (23.4-82.4). 44 % of ureteroscopies performed were flexible ureteroscopies, 31 % rigid ureteroscopies and 25 % associated rigid and flexible ureteroscopies. The average stone load was 10.1 +/- 5.7 mm (2-30) The mean operating time was 58.3 +/- 21.1 min (20-150). 82.9 % of patients had a single urinary stone and 17.1 % (n = 14) had 2 or more. 114 stones were treated, 57,1 % intrarenal. There were 6 (6 %) postoperative complications: three Clavien stage 2 infections; three Clavien stage 3b complications (two renal colics requiring ureteral stenting 48 h after discharge and 1 symptomatic perirenal urinoma 48 h after discharge). There was one intraoperative complication (1 %): a ureteral wound with contrast leakage. The rate of transfer to conventional hospitalization was 2.2 %. Stone size influenced the stone-free status (p < 0.0001) and the need for more than one session. There was a significant correlation between operative time and stone size above 10 mm (p < 0.0001). CONCLUSIONS: Flexible and rigid ureteroscopy are safe and efficient procedures for upper urinary tract stones and can be carried out in an outpatient department. Stone size had an impact on postoperative stone free status and operative time. PMID- 26822018 TI - The Cradle of Russian Hydrogeology: 85 Years of Groundwater Studies at the Leningrad Mining Institute. PMID- 26822019 TI - Attention-deficit/hyperactivity disorder-specific stimulant misuse, mood, anxiety, and stress in college-age women at high risk for or with eating disorders. AB - OBJECTIVE: To examine the misuse of attention-deficit/hyperactivity disorder (ADHD)-specific stimulants in a college population at high risk for or with clinical or subclinical eating disorders. PARTICIPANTS: Four hundred forty-eight college-age women aged 18-25 at high risk for or with a clinical or subclinical eating disorder. METHODS: Participants completed assessments of stimulant misuse and psychopathology from September 2009 to June 2010. RESULTS: Greater eating disorder pathology, objective binge eating, purging, eating disorder-related clinical impairment, depressive symptoms, perceived stress, and trait anxiety were associated with an increased likelihood of stimulant misuse. Subjective binge eating, excessive exercise, and dietary restraint were not associated with stimulant misuse. CONCLUSIONS: ADHD-specific stimulant misuse is associated with eating disorder and comorbid pathology among individuals at high risk for or with clinical or subclinical eating disorders. Screening for stimulant misuse and eating disorder pathology may improve identification of college-age women who may be engaging in maladaptive behaviors and inform prevention efforts. PMID- 26822021 TI - Sequential Michael addition/retro-Claisen condensation of aromatic beta-diketones with alpha,beta-unsaturated esters: an approach to obtain 1,5-ketoesters. AB - A K2CO3-catalyzed one-pot protocol involving sequential C-C bond formation and cleavage of aromatic beta-diketones with alpha,beta-unsaturated esters is developed to obtain 1,5-ketoesters. The sequential reaction via Michael addition and retro-Claisen condensation proceeds smoothly under mild conditions in up to 98% isolated yield. The mechanism study disclosed that the cascade process involved C-C bond cleavage of aromatic beta-diketone as a phenacyl donor under alcoholic alkalescent conditions. PMID- 26822020 TI - Taxonomy of haemolytic and/or proteolytic strains of the genus Acinetobacter with the proposal of Acinetobacter courvalinii sp. nov. (genomic species 14 sensu Bouvet & Jeanjean), Acinetobacter dispersus sp. nov. (genomic species 17), Acinetobacter modestus sp. nov., Acinetobacter proteolyticus sp. nov. and Acinetobacter vivianii sp. nov. AB - We aimed to define the taxonomic status of 40 haemolytic and/or proteolytic strains of the genus Acinetobacter which were previously classified into five putative species termed as genomic species 14BJ (n=9), genomic species 17 (n=9), taxon 18 (n=7), taxon 19 (n=6) and taxon 20 (n=9). The strains were recovered mostly from human clinical specimens or soil and water ecosystems and were highly diverse in geographical origin and time of isolation. Comparative analysis of the rpoB and gyrB gene sequences of all strains, and the whole-genome sequences of selected strains, showed that these putative species formed five respective, well supported clusters within a distinct clade of the genus Acinetobacter which typically, although not exclusively, encompasses strains with strong haemolytic activity. The whole-genome-based average nucleotide identity (ANIb) values supported the species status of each of these clusters. Moreover, the distinctness and coherence of the clusters were supported by whole-cell profiling based on MALDI-TOF MS. Congruent with these findings were the results of metabolic and physiological testing. We conclude that the five putative taxa represent respective novel species, for which the names Acinetobacter courvalinii sp. nov. (type strain ANC 3623T=CCUG 67960T=CIP 110480T=CCM 8635T), Acinetobacter dispersus sp. nov. (type strain ANC 4105T=CCUG 67961T=CIP 110500T=CCM 8636T), Acinetobacter modestus sp. nov. (type strain NIPH 236T=CCUG 67964T=CIP 110444T=CCM 8639T), Acinetobacter proteolyticus sp. nov. (type strain NIPH 809T=CCUG 67965T=CIP 110482T = CCM 8640T) and Acinetobacter vivianii sp. nov. (type strain NIPH 2168T=CCUG 67967T=CIP 110483T=CCM 8642T) are proposed. PMID- 26822023 TI - Weyl Mott Insulator. AB - Relativistic Weyl fermion (WF) often appears in the band structure of three dimensional magnetic materials and acts as a source or sink of the Berry curvature, i.e., the (anti-)monopole. It has been believed that the WFs are stable due to their topological indices except when two Weyl fermions of opposite chiralities annihilate pairwise. Here, we theoretically show for a model including the electron-electron interaction that the Mott gap opens for each WF without violating the topological stability, leading to a topological Mott insulator dubbed Weyl Mott insulator (WMI). This WMI is characterized by several novel features such as (i) energy gaps in the angle-resolved photo-emission spectroscopy (ARPES) and the optical conductivity, (ii) the nonvanishing Hall conductance, and (iii) the Fermi arc on the surface with the penetration depth diverging as approaching to the momentum at which the Weyl point is projected. Experimental detection of the WMI by distinguishing from conventional Mott insulators is discussed with possible relevance to pyrochlore iridates. PMID- 26822022 TI - Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: A randomized phase III study (ALLY-3+). AB - Patients with hepatitis C virus (HCV) genotype 3 infection, especially those with advanced liver disease, are a challenging population in urgent need of optimally effective therapies. The combination of daclatasvir (DCV; pangenotypic nonstructural protein 5A inhibitor) and sofosbuvir (SOF; nucleotide nonstructural protein 5B inhibitor) for 12 weeks previously showed high efficacy (96%) in noncirrhotic genotype 3 infection. The phase III ALLY-3+ study (N = 50) evaluated DCV-SOF with ribavirin (RBV) in treatment-naive (n = 13) or treatment-experienced (n = 37) genotype 3-infected patients with advanced fibrosis (n = 14) or compensated cirrhosis (n = 36). Patients were randomized 1:1 to receive open label DCV-SOF (60 + 400 mg daily) with weight-based RBV for 12 or 16 weeks. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12). SVR12 (intention-to-treat) was 90% overall (45 of 50): 88% (21 of 24) in the 12-week (91% observed) and 92% (24 of 26) in the 16-week group. All patients with advanced fibrosis achieved SVR12. SVR12 in patients with cirrhosis was 86% overall (31 of 36): 83% (15 of 18) in the 12-week (88% observed) and 89% (16 of 18) in the 16-week group; for treatment-experienced patients with cirrhosis, these values were 87% (26 of 30), 88% (14 of 16; 93% observed), and 86% (12 of 14), respectively. One patient (12-week group) did not enter post-treatment follow-up (death unrelated to treatment). There were 4 relapses (2 per group) and no virological breakthroughs. The most common adverse events (AEs) were insomnia, fatigue, and headache. There were no discontinuations for AEs and no treatment related serious AEs. CONCLUSION: The all-oral regimen of DCV-SOF-RBV was well tolerated and resulted in high and similar SVR12 after 12 or 16 weeks of treatment among genotype 3-infected patients with advanced liver disease, irrespective of past HCV treatment experience. PMID- 26822024 TI - Eosinophilic Fasciitis and Acute Encephalopathy Toxicity from Pembrolizumab Treatment of a Patient with Metastatic Melanoma. AB - Anti-PD-1 inhibitors have significant activity in metastatic melanoma. Responses often occur early and may be sustained. The optimal duration of treatment with these agents is unknown. Here, we report the case of a 51-year-old woman treated with pembrolizumab, as part of the Keynote-001 trial, as first-line treatment for metastatic disease. She experienced a complete response after 13.8 months of treatment with no adverse events. One month after the last drug infusion and 18 months from starting treatment, the patient presented with eosinophilic fasciitis. She then developed acute confusion and weakness, thought to be due to intracranial vasculitis. High-dose steroids were initiated with resolution of the fasciitis. Aspirin was commenced for presumed vasculitis with resolution of the neurologic symptoms. To our knowledge, there are no previous reports of eosinophilic fasciitis or cerebral vasculitis due to anti-PD-1 agents. This case demonstrates that toxicity may occur in association with pembrolizumab treatment after a prolonged period of treatment without toxicity. Future trials should explore the optimal duration of treatment with pembrolizumab. PMID- 26822026 TI - Abstracts from VASBI Annual Meeting, 24-25 September 2015, Manchester - UK. AB - Abstracts from the Annual Meeting of the Vascular Access Society of Britain and Ireland, 24-25 September 2015, Manchester - UK. PMID- 26822025 TI - CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains. AB - Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor in adults with a 5-year overall survival rate of less than 10%. Podoplanin (PDPN) is a type I transmembrane mucin-like glycoprotein, expressed in the lymphatic endothelium. Several solid tumors overexpress PDPN, including the mesenchymal type of GBM, which has been reported to present the worst prognosis among GBM subtypes. Chimeric antigen receptor (CAR)-transduced T cells can recognize predefined tumor surface antigens independent of MHC restriction, which is often downregulated in gliomas. We constructed a lentiviral vector expressing a third generation CAR comprising a PDPN-specific antibody (NZ-1-based single-chain variable fragment) with CD28, 4-1BB, and CD3zeta intracellular domains. CAR transduced peripheral blood monocytes were immunologically evaluated by calcein mediated cytotoxic assay, ELISA, tumor size, and overall survival. The generated CAR T cells were specific and effective against PDPN-positive GBM cells in vitro. Systemic injection of the CAR T cells into an immunodeficient mouse model inhibited the growth of intracranial glioma xenografts in vivo. CAR T-cell therapy that targets PDPN would be a promising adoptive immunotherapy to treat mesenchymal GBM. PMID- 26822028 TI - Novel exonic mutation inducing aberrant splicing in the IL10RA gene and resulting in infantile-onset inflammatory bowel disease: a case report. AB - BACKGROUND: Although deleterious mutations in interleukin-10 and its receptor molecules cause severe infantile-onset inflammatory bowel disease, there are no reports of mutations affecting this signaling pathway in Japanese patients. Here we report a novel exonic mutation in the IL10RA gene that caused unique splicing aberrations in a Japanese patient with infantile-onset of inflammatory bowel disease in association with immune thrombocytopenic purpura and a transient clinical syndrome mimicking juvenile myelomonocytic leukemia. CASE PRESENTATION: A Japanese boy, who was the first child of non-consanguineous healthy parents, developed bloody diarrhea, perianal fistula, and folliculitis in early infancy and was diagnosed with inflammatory bowel disease. He also developed immune thrombocytopenic purpura and transient features mimicking juvenile myelomonocytic leukemia. The patient failed to respond to various treatments, including elemental diet, salazosulfapyridine, metronidazole, corticosteroid, infliximab, and adalimumab. We identified a novel mutation (c.537G > A, p.T179T) in exon 4 of the IL10RA gene causing unique splicing aberrations and resulting in lack of signaling through the interleukin-10 receptor. At 21 months of age, the patient underwent allogeneic hematopoietic stem cell transplantation and achieved clinical remission. CONCLUSIONS: We describe a novel exonic mutation in the IL10RA gene resulting in infantile-onset inflammatory bowel disease. This mutation might also be involved in his early-onset hematologic disorders. Physicians should be familiar with the clinical phenotype of IL-10 signaling defects in order to enable prompt diagnosis at an early age and referral for allogeneic hematopoietic stem cell transplantation. PMID- 26822027 TI - An integrative genome-wide transcriptome reveals that candesartan is neuroprotective and a candidate therapeutic for Alzheimer's disease. AB - BACKGROUND: Alzheimer's disease is the most frequent age-related dementia, and is currently without treatment. To identify possible targets for early therapeutic intervention we focused on glutamate excitotoxicity, a major early pathogenic factor, and the effects of candesartan, an angiotensin receptor blocker of neuroprotective efficacy in cell cultures and rodent models of Alzheimer's disease. The overall goal of the study was to determine whether gene analysis of drug effects in a primary neuronal culture correlate with alterations in gene expression in Alzheimer's disease, thus providing further preclinical evidence of beneficial therapeutic effects. METHODS: Primary neuronal cultures were treated with candesartan at neuroprotective concentrations followed by excitotoxic glutamate amounts. We performed genome-wide expression profile analysis and data evaluation by ingenuity pathway analysis and gene set enrichment analysis, compared with alterations in gene expression from two independent published datasets identified by microarray analysis of postmortem hippocampus from Alzheimer's disease patients. Preferential expression in cerebrovascular endothelial cells or neurons was analyzed by comparison to published gene expression in these cells isolated from human cortex by laser capture microdissection. RESULTS: Candesartan prevented glutamate upregulation or downregulation of several hundred genes in our cultures. Ingenuity pathway analysis and gene set enrichment analysis revealed that inflammation, cardiovascular disease and diabetes signal transduction pathways and amyloid beta metabolism were major components of the neuronal response to glutamate excitotoxicity. Further analysis showed associations of glutamate-induced changes in the expression of several hundred genes, normalized by candesartan, with similar alterations observed in hippocampus from Alzheimer's disease patients. Gene analysis of neurons and cerebrovascular endothelial cells obtained by laser capture microdissection revealed that genes up- and downregulated by glutamate were preferentially expressed in endothelial cells and neurons, respectively. CONCLUSIONS: Our data may be interpreted as evidence of direct candesartan neuroprotection beyond its effects on blood pressure, revealing common and novel disease mechanisms that may underlie the in vitro gene alterations reported here and glutamate-induced cell injury in Alzheimer's disease. Our observations provide novel evidence for candesartan neuroprotection through early molecular mechanisms of injury in Alzheimer's disease, supporting testing this compound in controlled clinical studies in the early stages of the illness. PMID- 26822030 TI - Exome sequencing identifies a mutation in TMC1 as a novel cause of autosomal recessive nonsyndromic hearing loss. AB - BACKGROUND: Autosomal recessive non-syndromic hearing loss (ARNSHL) is highly heterogeneous, and mutations in the gene encoding transmembrane channel-like 1 (TMC1) have been implicated in its development. To date, 35 homozygous mutations in TMC1, identified in over 60 families worldwide, have been shown to be associated with ARNSHL. However, few of these mutations were detected in the Chinese population. In this study, we describe a pathogenic missense mutation located in the T5-T6 domain of TMC1 in a three-generation Chinese family with 14 members. METHODS: Whole exome sequencing was performed using samples from one unaffected individual and two affected individuals to systematically search for deafness susceptibility genes. Candidate mutations and cosegregation of the phenotype were verified by polymerase chain reaction and Sanger sequencing in all of the family members. RESULTS: We identified a novel TMC1 mutation in exon 20, c.1979C>T, p.P660L, which segregated with prelingual autosomal recessive sensorineural hearing loss. CONCLUSIONS: We found a new missense mutation in the T5-T6 domain of TMC1, which is highly conserved in many species. These data support the potential conserved role of p.P660L in human TMC1 function. PMID- 26822031 TI - Tau-directed approaches for the treatment of Alzheimer's disease: focus on leuco methylthioninium. AB - Small molecular weight compounds able to inhibit formation of tau oligomers and fibrils have already been tested for Alzheimer's disease (AD) treatment. The most advanced tau aggregation inhibitor (TAI) is methylthioninium (MT), a drug existing in equilibrium between a reduced (leuco-methylthioninium) and oxidized form (MT(+)). MT chloride (also known as methylene blue) was investigated in a 24 week Phase II study in 321 mild-to-moderate AD patients at the doses of 69, 138, and 228 mg/day. This trial failed to show significant positive effects of MT in the overall patient population. The dose of 138 mg/day showed potential benefits on cognitive performance of moderately affected patients and cerebral blood flow in mildly affected patients. A follow-up compound (TRx0237) claimed to be more bioavailable and less toxic than MT, is now being developed. Phase III clinical trials on this novel TAI in AD and in the behavioral variant of frontotemporal dementia are underway. PMID- 26822032 TI - Precision Therapy for Pediatric Cancers. PMID- 26822033 TI - Intersectoral collaboration to implement school-based health programmes: Australian perspectives. AB - Understanding the processes and the factors influencing intersectoral collaboration is vital for the ongoing success of programmes that rely on effective partnerships between sectors, such as the school-based immunization programme, the school dental health programme and health promotion interventions delivered in school settings. We studied school-based health programmes delivered by partnerships between health, education and the local government sectors. We used purposive sampling to identify 19 people working in school-based health programmes and interviewed them about the barriers and enablers of successful collaboration. Data were analysed thematically. We found that collaboration between complex systems was a skilled endeavour which relied on a strong foundation of communication and interpersonal professional relationships. Understanding the core business, operational context and intersectoral point-of view of collaborative partners was important both for establishing good intersectoral programmes and sustaining them as contexts and personnel changed. Aligning divergent sectoral agendas early in the collaborative process was essential for ensuring that all partners could meet their core business needs while also delivering the programme outcomes. PMID- 26822035 TI - Exploring the motion advantage: evaluating the contribution of familiarity and differences in facial motion. AB - Seeing a face move can improve familiar face recognition, face matching, and learning. More specifically, familiarity with a face may facilitate the learning of an individual's "dynamic facial signature". In the outlined research we examine the relationship between participant ratings of familiarity, the distinctiveness of motion, the amount of facial motion, and the recognition of familiar moving faces (Experiment 1) as well as the magnitude of the motion advantage (Experiment 2). Significant positive correlations were found between all factors. Findings suggest that faces rated as moving a lot and in a distinctive manner benefited the most from being seen in motion. Additionally findings indicate that facial motion information becomes a more important cue to recognition the more familiar a face is, suggesting that "dynamic facial signatures" continue to be learnt over time and integrated within the face representation. Results are discussed in relation to theoretical explanations of the moving face advantage. PMID- 26822034 TI - Inactivation of nuclear GSK3beta by Ser(389) phosphorylation promotes lymphocyte fitness during DNA double-strand break response. AB - Variable, diversity and joining (V(D)J) recombination and immunoglobulin class switch recombination (CSR) are key processes in adaptive immune responses that naturally generate DNA double-strand breaks (DSBs) and trigger a DNA repair response. It is unclear whether this response is associated with distinct survival signals that protect T and B cells. Glycogen synthase kinase 3beta (GSK3beta) is a constitutively active kinase known to promote cell death. Here we show that phosphorylation of GSK3beta on Ser(389) by p38 MAPK (mitogen-activated protein kinase) is induced selectively by DSBs through ATM (ataxia telangiectasia mutated) as a unique mechanism to attenuate the activity of nuclear GSK3beta and promote survival of cells undergoing DSBs. Inability to inactivate GSK3beta through Ser(389) phosphorylation in Ser(389)Ala knockin mice causes a decrease in the fitness of cells undergoing V(D)J recombination and CSR. Preselection-Tcrbeta repertoire is impaired and antigen-specific IgG antibody responses following immunization are blunted in Ser(389)GSK3beta knockin mice. Thus, GSK3beta emerges as an important modulator of the adaptive immune response. PMID- 26822036 TI - Nuclear Mechanisms of Insulin Resistance. AB - Insulin resistance is a sine qua non of type 2 diabetes and is associated with many other clinical conditions. Decades of research into mechanisms underlying insulin resistance have mostly focused on problems in insulin signal transduction and other mitochondrial and cytosolic pathways. By contrast, relatively little attention has been focused on transcriptional and epigenetic contributors to insulin resistance, despite strong evidence that such nuclear mechanisms play a major role in the etiopathogenesis of this condition. In this review, we summarize the evidence for nuclear mechanisms of insulin resistance, focusing on three transcription factors with a major impact on insulin action in liver, muscle, and fat. PMID- 26822037 TI - Bicaudal D Family of Motor Adaptors: Linking Dynein Motility to Cargo Binding. AB - Transport of different intracellular cargoes along cytoskeleton filaments is essential for the morphogenesis and function of a broad variety of eukaryotic cells. Intracellular transport is mediated by cytoskeletal motors including myosin, kinesin, and dynein, which are typically linked to various cargoes by adaptor proteins. Recent studies suggest that adaptor proteins can also act as essential transport cofactors, which control motor activity and coordination. Characterization of the evolutionary conserved Bicaudal D (BICD) family of dynein adaptor proteins has provided important insights into the fundamental mechanisms governing cargo trafficking. This review highlights the advances in the current understanding of how BICD adaptors regulate microtubule-based transport and how they contribute to developmental processes and human disease. PMID- 26822038 TI - Predicting Postoperative Complications After Pediatric Perforated Appendicitis. AB - PURPOSE: Assessment of risk factors for postoperative complications following surgical treatment of pediatric perforated appendicitis (PA) is necessary to identify those patients in need of closer monitoring. In this study, we have investigated the impact of different risk factors on the occurrence of complications after an appendectomy in children with PA. MATERIAL AND METHODS: The study was a retrospective, single-centre analysis of all pediatric PA conducted over a 10-year period. Preoperative clinical and laboratory results, intraoperative findings, and postoperative complications were analyzed. Risk factors were defined and a risk score was determined for postoperative complications and reinterventions. RESULTS: Surgical treatment for appendicitis was performed in 840 pediatric patients during the observation period. 163 of the included patients were diagnosed with PA (mean age 8.9 +/- 3.6 years). 19 (11.7%) patients developed postoperative complications, 17 (10.4%) of which required complication-related intervention. We identified five predictors of postoperative complications: the C-related protein value at admission, purulent peritonitis, open appendectomy (primary, secondary, or converted), placement of an abdominal drain, and administration of antibiotics not compliant to results from the subsequent antibiogram. The determined risk score was significantly higher in the complication group (p < .0001) and reintervention group (p < .001). CONCLUSIONS: Postoperative complications following pediatric PA can be predicted using specific preoperative, intraoperative, and postoperative risk factors. In the high-risk group, an active prevention, detection, and intervention of any occurring complication is necessary and we present a new specific pediatric risk score to define patients at risk for complications. PMID- 26822039 TI - Camouflage predicts survival in ground-nesting birds. AB - Evading detection by predators is crucial for survival. Camouflage is therefore a widespread adaptation, but despite substantial research effort our understanding of different camouflage strategies has relied predominantly on artificial systems and on experiments disregarding how camouflage is perceived by predators. Here we show for the first time in a natural system, that survival probability of wild animals is directly related to their level of camouflage as perceived by the visual systems of their main predators. Ground-nesting plovers and coursers flee as threats approach, and their clutches were more likely to survive when their egg contrast matched their surrounds. In nightjars - which remain motionless as threats approach - clutch survival depended on plumage pattern matching between the incubating bird and its surrounds. Our findings highlight the importance of pattern and luminance based camouflage properties, and the effectiveness of modern techniques in capturing the adaptive properties of visual phenotypes. PMID- 26822040 TI - [Highlights of the third edition of Chinese guidelines for AIDS diagnosis and treatment(2015)]. AB - The third edition of Chinese guidelines for AIDS diagnosis and treatment was launched in 2015 by AIDS Professional Group, Society of Infectious Diseases, Chinese Medical Association. New edition emphasizes the importance of timely initiation of anti-retroviral therapy(ART). Like other guidelines, this edition recommends that once the HIV infection is confirmed, the ART should be initiated timely. For patients with HIV and opportunistic infections, once the infections are under control, the ART should be initiated without delay. For AIDS patients complicated with tuberculosis whose CD4 cell counts are less than 200/MUL, the ART should start within 2 weeks after the initiation of anti-tuberculosis treatment. In this guideline, the drugs with severe toxicities and poor tolerance are excluded, and new drugs are added such as rilpivrine (RPV) and atazanavir (ATV) because of less toxicity and higher HIV depression effect; and 3TC+TDF+EFV is recommended as the first line regimen. As for children with HIV infection, especially for those less than 5 years, once the infection is confirmed the ART should be initiated immediately. For the prevention of HIV mother to children transmission, new edition recommends that HIV-infected pregnant women start ART early and keep on ART all their lives. PMID- 26822041 TI - [Relationship between early blood pressure variability and reperfusion in acute ischemic stroke patients with intravenous thrombolysis]. AB - OBJECTIVE: To investigate the impacts of blood pressure (BP) variability on reperfusion and long-term outcome in patients with acute ischemic stroke after intravenous thrombolysis (IVT). METHODS: The clinical data of 188 patients with acute ischemic stroke receiving IVT in Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2009 to September 2014, including hour-to-hour BP measurements, clinical manifestations, laboratory tests and radiologic findings were retrospectively analyzed. The mean 24-h BP values, and BP variability profiles, including standard deviation (sd), average squared difference between successive measurements (sv), average squared difference between rise and drop successive measurements (sv-rise and sv-drop) were calculated. Reperfusion, defined as >50% reduction in Tmax >6 s perfusion lesion volume from baseline to follow-up scans, and clinical neurological outcome based on modified Rankin scale (mRS) at 3 months after onset were also analyzed. The favorable outcome was defined as mRS 0-1 and unfavorable outcome as mRS 2-6. The binary logistic-regression model was performed to determine the independent risk factors of reperfusion and favorable outcome, respectively. RESULTS: Among 188 patients, 114 (60.6%) achieved reperfusion. During the 0-to-24 h blood pressure course, only systolic blood pressure (SBP) variability parameters were negatively correlated with reperfusion (sv: OR=0.421, 95% CI:0.187-0.950, P=0.037; sv-rise: OR=0.311, 95% CI:0.137-0.704, P=0.005) and long-term clinical outcomes (sv: OR=6.381, 95% CI:2.132-19.096, P=0.001; sv-rise: OR=5.615, 95% CI:2.152-14.654, P<0.001; sv-drop: OR=3.009, 95% CI:1.263-7.169, P=0.013). CONCLUSION: SBP variability during the first 24 hours after IVT is negatively associated with cerebral reperfusion and unfavorable neurological outcome in patients with acute ischemic stroke receiving IVT. PMID- 26822042 TI - [Thrombus length evaluated by CT perfusion imaging and its value in prediction of recanalization after intravenous thrombolysis therapy]. AB - OBJECTIVE: To evaluate the thrombus length on CT perfusion imaging and to assess its predictive value for recanalization and clinical outcome after intravenous thrombolysis therapy (IVT). METHODS: Fifty-six consecutive acute ischemic stroke patients with proximal middle cerebral artery (M1 segment) occlusion underwent CT perfusion imaging examination before IVT between June 2009 and May 2015. The onset-to needle time was (214.3 +/- 82.0) min, and the pretreatment NIHSS score of patients was 13 (IQR 8-17). The thrombus length was determined as the distance between the proximal and distal thrombus end delineated on dynamic angiography, which was reconstructed from CT perfusion source images. Recanalization was evaluated according to Arterial Occlusive Lesion (AOL) scale, and functional outcome was based on modified Rankin scale (mRS) 3 months after IVT. Logistic regression model was used to investigate the relationship between thrombus length and recanalization, and the optimal cut-off points were determined by receiver operating characteristic curve (ROC). RESULTS: Among 56 patients, 42 (75%) achieved recanalization 24 h after IVT with mean thrombus length of (9.0 +/- 4.7) mm; and 14 (25%) patients remained occlusion with mean thrombus length of (10.0 +/- 5.4) mm. Logistic regression analysis demonstrated that thrombus length was an independent predictor for both recanalization (OR=0.869; 95% CI:0.764-0.987; P=0.031) and unfavorable outcome (OR=1.180;95% CI:1.023-1.362; P=0.023). Thrombus length of 11.3 mm was identified as the optimal cut-off value for recanalization (AUC=0.697, sensitivity 71.4%, specificity 76.2%), while thrombus length of 9.9 mm was the optimal cut-off value for unfavorable functional outcome (AUC=0.689, sensitivity 64.7%, specificity 71.4%). CONCLUSION: The thrombus length evaluated on CT perfusion imaging is an effective predictor for recanalization and unfavorable outcome after IVT in acute ischemic stroke patients with middle cerebral artery occlusion. PMID- 26822043 TI - [Safety of intravenous thrombolysis in cerebral microbleeds patients with prior antiplatelet therapy]. AB - OBJECTIVE: To evaluate the safety of intravenous thrombolysis (IVT) in cerebral microbleeds (CMBs) patients with prior antiplatelet therapy. METHODS: Four hundred and forty nine patients with acute ischemic stroke aged (66.8 +/- 12.9) years, including 298 males and 151 females, underwent susceptibility-weighted imaging (SWI) examination and MRI-guided IVT therapy between June 2009 and June 2015. The presence of CMBs, previous antiplatelet therapy, HT subtypes according to ECASS II criteria and functional outcome based on modified Rankin scale (mRS) at 3 months were analyzed in logistic regression model. RESULTS: Total 934 CMBs were detected in 172 (38.3%) patients, among whom 63 (14.0%) previously received antiplatelet therapy. All patients received intravenous recombinant tissue plasminogen activator (rt-PA) for thrombolysis with the onset-to needle time of (229.0 +/- 103.7) min. The pretreatment National Institutes of Health Stroke Scale (NIHSS) score was 10 (IQR 5-15). Logistic regression analysis indicated that prior antiplatelet use increased neither risk of parenchymal hematoma (PH) (OR=0.809,95% CI:0.201-3.262, P=0.766) nor adverse functional outcome (OR=1.517, 95% CI:0.504-4.568, P=0.459) in patients with CMBs; while in patients with multiple CMBs (>= 3) prior antiplatelet use increased risk of hemorrhagic transformation (OR=9.737, 95% CI: 1.364-69.494, P=0.023), but not adverse functional outcome (OR=1.697, 95% CI:0.275-10.487, P=0.569). CONCLUSION: The study indicates that in patients with CMBs, thrombolytic therapy should not be excluded due to the prior use of antiplatelet; however, the larger prospective studies are needed in future for patients with multiple CMBs. PMID- 26822044 TI - [Signifiance of brush sign on susceptibility-weighted imaging predicts hemorrhagic transformation after intravenous thrombolysis in patients with acute ischemic stroke]. AB - OBJECTIVE: To assess brush sign (BS) on susceptibility-weighted imaging (SWI) in prediction of hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis(IVT). METHODS: Patients with acute cerebral ischemic stroke, who had major cerebral artery occlusion (internal carotid artery, middle cerebral artery M1 and M2), treated with intravenous recombinant tissue plasminogen activator (rt-PA) from August 2009 to October 2014 in the Second Affiliated Hospital, Zhejiang University School of Medicine, were enrolled in the study. All patients underwent SWI scanning. The asymmetry index (AI) was defined as the difference of intensity between ischemic and normal hemispheres on the SWI phase map; according to AI values patients were divided into 3 groups: BS=0(n=9), BS=1 (n=39) and BS=2 (n=18). The relationships between BS and HT and the clinical outcome among the 3 groups were analyzed. RESULTS: Sixty-six patients aged 68 +/- 13 years were included in the study, including 44 males (67%) and 22 females (33%), and 44 (67%) with acute ischemic stroke. The mean pre-treatment National Institutes of Health Stroke Scale (NIHSS) score was 13 (6-17), and the onset to needle time was (252 +/- 88) min. Twenty-six (39.4%) patients had HT, including 18 cases (27.3%) with HI and 8 cases (12.1%) with PH; BS was observed more frequently in HT group than non-HT group. Binary logistic regression analysis showed that BS was independently associated with HT of patients with acute ischemic stroke following IVT (OR=2.589, 95% CI: 1.080-6.210, P=0.033). In those without reperfusion after IVT, patients with higher BS grade had higher HT rate (P=0.023). CONCLUSION: Brush sign on SWI can be used for predicting hemorrhagic transformation after intravenous thrombolysis in patients with acute ischemic stroke. PMID- 26822045 TI - [Cerebral lesions of DWI hyperintensity in patients with subacute stroke assessed by intravoxel incoherent motion technique]. AB - OBJECTIVE: To investigate the cerebral lesions of diffusion weighted imaging (DWI) hyperintensity in patients with subacute stroke with intravoxel incoherent motion (IVIM) technique. METHODS: The clinical data of 20 patients with ischemic stroke (3 to 7 d after onset) who underwent DWI and IVIM scanning between June 2014 and July 2015, were retrospectively analyzed. The parameters from IVIM including slow diffusion coefficient (D), fast diffusion coefficient (D(*)) and perfusion fraction (f) were processed. DWI hyperintensity was segmented by its signal intensity greater than the mean+2 standard deviations of the value in the homologous contralateral region. Then, DWI hyperintensity was classified into two regions of interest (ROIs): infarction core and peri-core with the ADC threshold of 0.55 * 10-3 mm2/s. The mirrored ROIs of infarction core and peri-core were also obtained. Then, we measured the values of ADC and D, D(*) and f in these ROIs. The ratios of ADC (rADC), D (rD), D(*) (rD(*)) and f (rf) were also calculated (e.g., rADC=ADCinfarction core/ADCmirrored region). RESULTS: Compared with mirrored region, ADC, D and f in the infarction core region decreased by 45% (P<0.001), 42% (P<0.001) and 32% (P<0.001), respectively; while ADC, D and f in the peri-core region decreased by 22% (P<0.001), 32% (P<0.001) and 8% (P=0.009), respectively. The values of rADC, rD, rD(*) and rf in the infarction core region were significantly lower than those in the peri-core region (all P<0.001). Pearson analysis showed that rADC was positively correlated with rf in the peri core region (r=0.467, P=0.038). CONCLUSION: During subacute stage of stroke, compared to the infarction core region within DWI hyperintensity, D and f increase in the peri-core region of DWI hyperintensity, reflecting the increased water diffusion in microstructure and perfusion volume in microvasculature. This result shows that the potential reason for the heterogeneous ADC signal is associated with the disappearance of cellular edema and microvascular compensatory with increased blood volume. PMID- 26822046 TI - [Older age is not related to hemorrhagic transformation and favorable outcomes in patients with wake-up ischemic stroke undergoing intravenous thrombolytic therapy]. AB - OBJECTIVE: To investigate factors related to hemorrhagic transformation and favorable outcomes in wake-up ischemic stroke (WUIS) patients undergoing intravenous thrombolytic therapy. METHODS: Clinical data of 600 patients undergoing multimodal image-guided intravenous recombinant tissue plasminogen activator (rt-PA) therapy in Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine center from May 2009 to May 2015 were retrospectively analyzed. Among 600 patients, 68 were diagnosed as WUIS including 17 cases aged 80 or older. Hemorrhagic transformation within the first 24 h after thrombolysis was assessed according to ECASS II criteria. Favorable outcome was defined as three-month modified Rankin Scale (mRS) 0-3. Univariate and binary logistic regression were used to analyze the risk factors of hemorrhagic transformation and poor clinical outcomes in WUIS patients. RESULTS: Univariate analysis showed that WUIS patients aged >= 80 years had a lower rate in males (41.2% vs 76.5%, P=0.007), smokers (11.8% vs 43.1%, P=0.019) and favorable outcome (52.9% vs 78.4%, P=0.043); and a higher rate of cardiac embolism (64.7% vs 35.3%, P=0.034) compared with those aged <80 years. Binary logistic regression showed that age was not an independent risk factor for favorable outcome (OR=0.524, 95% CI:0.141-1.953, P=0.336) or hemorrhagic transformation (OR=1.039, 95% CI: 0.972-1.111, P=0.262). CONCLUSION: Older age is not related to the favorable outcome or hemorrhagic transformation in WUIS patients undergoing multimodal image-guided intravenous thrombolytic therapy. PMID- 26822047 TI - [Semi-quantitative risk assessment on local transmission of Dengue fever caused by introduced cases]. AB - OBJECTIVE: To assess the risk of local transmission of Dengue caused by introduced cases with semi-quantitative method in 2015 in Zhejiang Province. METHODS: Risk indexes of local transmission of Dengue caused by introduced cases were reviewed. The weights of indexes were computed by analytic hierarchy process and further used to generate absolute risk values by multiplying indexes. Moreover, comprehensive indexes were computed to describe relative risk by combining analytic hierarchy process and TOPSIS methods. RESULTS: Four primary indexes and 19 secondary indexes were identified for risk assessment of local transmission of Dengue. The indexes with maximum and minimum weight were the number of immigration from countries with Dengue patients (weight value: 0.0678) and density of population (weight value: 0.0371) respectively. All CR values, statistics for measuring consistency of score matrix, were less than 0.1 (minimum: 0.000, maximum: 0.0922, average: 0.0251). The absolute risk of Zhejiang Province was within the range of 0.397-0.504 (the full score was 1.0). The risk orders of 11 municipalities sorted by relative comprehensive indexes and absolute risk values methods were similar. The three highest municipalities were Hangzhou, Wenzhou and Ningbo and the ranges of absolute risk value were 0.387-0.494, 0.404 0.511 and 0.392-0.499 respectively. CONCLUSION: The results provides scientific basis for preventing and controlling Dengue in Zhejiang Province. The indexes and weights may be used to assess risk of Dengue in future. In addition, the semi quantitative method constructed in this study would be a significant reference for risk assessment of public health in emergencies. PMID- 26822048 TI - [Construction of early warning model of influenza-like illness in Zhejiang Province based on support vector machine]. AB - OBJECTIVE: To construct a forecasting model of influenza-like illness in Zhejiang Province. METHODS: The number of influenza-like cases and related pathogens among outpatients and emergency patients were obtained from 11 sentinel hospitals in Zhejiang Province during 2012 to 2013 (total 104 weeks), and corresponding meteorological factors were also collected. The epidemiological characteristics of influenza during the period were then analyzed. Linear correlation and rank correlation analyses were conducted to explore the association between influenza like illness and related factors. Optimal parameters were selected by cross validation. Support vector machine was used to construct the forecasting model of influenza-like illness in Zhejiang Province and verified by the historical data. RESULTS: Correlation analysis indicated that 8 factors were associated with influenza-like illness occurred in one week. The results of cross validation showed that the optimal parameters were C=3, epsilon=0.009 and gamma=0.4. The results of influenza-like illness forecasting model after verification revealed that support vector machine had the accuracy of 50.0% for prediction with the same level, while it reached 96.7% for prediction within the range of one level higher or lower. CONCLUSION: Support vector machine is suitable for early warning of influenza-like illness. PMID- 26822049 TI - [Prognostic value of Picco monitoring combined with plasma microRNA-150 detection in septic shock patients]. AB - OBJECTIVE: To assess the prognostic value of pulse indicator continuous cardiac output (Picco) monitoring combined with plasma microRNA-150 detection in septic shock patients. METHODS: Clinical data of 48 patients with septic shock admitted in General Intensive Care Unit (GICU), Shanghai First People's Hospital Songjiang Branch Affiliated to Shanghai Jiaotong University from August 2012 to August 2014 were analyzed retrospectively. The plasma levels of microRNA-150 in 48 patients at admission were assayed by qRT-PCR; and Picco monitoring was performed to record hemodynamic changes. The correlation of microRNA-150 or Picco parameters with prognosis of patients was assessed by univariate analysis and multivariate logistic analysis. Spearman correlation test showed the relationship between microRNA-150 and Picco parameters. Finally, the clinical value of combining microRNA-150 with Picco monitoring to predict the outcome of septic shock patients was analyzed by ROC curves. RESULTS: Twenty-three patients survived and 25 died in 28 d after admission in GICU. Compared with survival patients, microRNA-150 was significantly lower in fatal patients (t=-10.32, P<0.05). Univariate analysis showed that low microRNA-150 level was a risk factor for poor prognosis(OR=2.176,95% CI:1.121-4.223, P<0.05). Compared with fatal cases, the cardiac index of survival patients was higher, while EVLWI and PVPI were lower. MicroRNA-150 level was positively correlated with cardiac index (r=0.712, P<0.05), negatively correlated with EVLWI and PVPI (r=-0.622 and-0.689, both P<0.05). ROC curves showed a satisfactory diagnostic efficiency of combining microRNA-150 with Picco monitoring. CONCLUSION: Lower microRNA-150 may indicate a poor prognosis, and Picco monitoring combined with microRNA 150 detection may improve the prognostic efficiency in septic shock patients. PMID- 26822050 TI - [Preparation and performance characterization of pseudo-ginseng entrapped in crosslinked chitosan/polyacrylic acid/poly(ethylene oxide) nanofibrous membrane]. AB - OBJECTIVE: To prepare the cross-linked chitosan/poly(acrylic acid)/poly (ethylene oxide) nanofibrous membrance loaded with pseudo-ginseng and to determine its characteristics. METHODS: Pseudo-ginseng entrapped in chitosan, poly (acrylic acid), poly (ethylene oxide) nanofibrous membrane loaded with pseudo-ginseng was prepared by electrospinning and thermal treatment method. The surface morphology of fiber membrane was observed by scanning electron microscopy and the chemical structures were characterized by infrared spectroscopy; the thermal decomposition temperature was analyzed by the thermogravimetric analysis. UV-Vis spectra were used to evaluate the in vitro release properties. RESULTS: The average diameter of the prepared nanofibrous particles was (181 +/- 71) nm. The tensile strength of fiber membrane increased by 35.3% and the decomposition temperature increased from 197C to 208C after crosslinking. Compared with casting film, the structure of fiber membrane increased the release rate and the overall amount of active components from pseudo-ginseng. CONCLUSION: The preparation of chitosan fiber loaded with pseudo-ginseng is simple and the dispersion of pseudo-ginseng is homogeneous. This fibrous pseudo-ginseng exhibited good release performance, providing a new Chinese medicine formulation. PMID- 26822051 TI - [Research advances of anti-tumor immune response induced by pulse electric field ablation]. AB - As a novel tumor therapy, pulse electric field has shown a clinical perspective. This paper reviews the characteristics of tumor ablation by microsecond pulse and nanosecond pulse electric field, and the research advances of anti-tumor immune response induced by pulse electric field ablation. Recent researches indicate that the pulse electric field not only leads to a complete ablation of local tumor, but also stimulates a protective immune response, thereby inhibiting tumor recurrence and metastasis. These unique advantages will show an extensive clinical application in the future. However, the mechanism of anti-tumor immune response and the development of related tumor vaccine need further studies. PMID- 26822052 TI - [Mechanism of ablation with nanosecond pulsed electric field]. AB - Nanosecond pulsed electric field ablation has been widely applied in clinical cancer treatment, while its molecular mechanism is still unclear. Researchers have revealed that nanosecond pulsed electric field generates nanopores in plasma membrane, leading to a rapid influx of Ca2+; it has specific effect on intracellular organelle membranes, resulting in endoplasmic reticulum injuries and mitochondrial membrane potential changes. In addition, it may also change cellular morphology through damage of cytoskeleton. This article reviews the recent research advances on the molecular mechanism of cell membrane and organelle changes induced by nanosecond pulsed electric field ablation. PMID- 26822053 TI - [Gap junction and diabetic foot]. AB - Gap junctions play a critical role in electrical synchronization and exchange of small molecules between neighboring cells; connexins are a family of structurally related transmembrane proteins that assemble to form vertebrate gap junctions. Hyperglycemia changes the structure gap junction proteins and their expression, resulting in obstruction of neural regeneration, vascular function and wound healing, and also promoting vascular atherosclerosis. These pathogenic factors would cause diabetic foot ulcers. This article reviews the involvement of connexins in pathogenesis of diabetic foot. PMID- 26822054 TI - [Efficacy of family intervention in management of schizophrenic patients in China: a meta-analysis]. AB - OBJECTIVE: To assess the efficacy of family intervention in management of schizophrenic patients in China. METHODS: Chinese databases CNKI, VIP, WANFANG, CBM and English databases OVID Medline, Science Direct, Web of science, EBSCO were searched systematically from inception to January 2015. Quantitative and empirical studies on the outcomes of social disability screening scale (SDSS), brief psychiatric rating scale (BPRS) and positive and negative syndrome scale (PANSS) of family intervention for Chinese schizophrenic patients were selected. The effect size was derived from the standardized mean difference (SMD), and meta analysis was conducted to compare effects of family intervention by intervention types, time of intervention, durations of illness and severity of schizophrenia. RESULTS: The study included 57 articles that met inclusion criteria. SDSS and PANSS scores revealed that the effect was positively associated with the length of intervention time (P<0.0001, P=0.0025); the effect of single family intervention was better than that of combined single and multiple family intervention (P<0.0001, P=0.0131); the effect was better for patients with severe conditions than those with less severe conditions (P<0.0001, P=0.0280). The SDSS showed that the effect was better for patients with shorter disease duration (P<0.0001). CONCLUSION: The results suggest that the long single family intervention would benefit to schizophrenic patients, particularly for severe patients with short disease duration. PMID- 26822055 TI - [Topics of World Gastroenterology Organization International Congress and United European Gastroenterology Week in 2015]. PMID- 26822056 TI - Both Talin-1 and Talin-2 correlate with malignancy potential of the human hepatocellular carcinoma MHCC-97 L cell. AB - BACKGROUND: Talin-1 (TLN-1) and TLN-2 are implicated in many cellular processes, but their roles in hepatocellular carcinoma (HCC) remain unclear. This study aimed to assess cell cycle distribution, anoikis, invasion and migration in human HCC MHCC-97 L cells. METHODS: MHCC-97 L cells, which highly express TLN-1, were transduced with TLN-1 shRNA (experimental group) or scramble shRNA (negative control group); non-transduced MHCC-97 L cells were used as blank controls. TLN-1 and TLN-2 mRNA and protein levels were detected by real-time RT-PCR and western blot, respectively. Then, cell cycle distribution and anoikis were assessed by flow cytometry. In addition, migration and invasion abilities were assessed using Transwell and cell scratch assays. Finally, a xenograft nude mouse model was established to further assess cell tumorigenicity. RESULTS: Compared with the blank and negative control groups, TLN-1/2 mRNA and protein levels were significantly reduced in the experiment group. TLN-1/2 knockdown cells showed significantly more cells in the G0/G1 phase (79.24%) in comparison with both blank (65.36%) and negative (62.69%) control groups; conversely, less cells were found in G2/M and S phases in the experimental group compared with controls. Moreover, anoikis was enhanced (P < 0.05), while invasion and migration abilities were reduced (P < 0.05) in TLN-1/2 knockdown cells compared with controls. TLN 1/2 knockdown inhibited MHCC-97 L cell migration (Percentage of wound healing area: experimental group: 32.6 +/- 0.7% vs. negative controls: 50.1 +/- 0.6% and blank controls: 53.6 +/- 0.6%, both P < 0.01). Finally, the tumors obtained with TLN-1/2 knockdown cells were smaller (P < 0.05) compared with controls. CONCLUSION: Both TLN-1 and TLN-2 levels correlate with tumorigenicity in human HCC, indicating that these molecules constitute important molecular targets for the diagnosis and/or treatment of HCC. PMID- 26822057 TI - The beta2 clamp in the Mycobacterium tuberculosis DNA polymerase III alphabeta2epsilon replicase promotes polymerization and reduces exonuclease activity. AB - DNA polymerase III (DNA pol III) is a multi-subunit replication machine responsible for the accurate and rapid replication of bacterial genomes, however, how it functions in Mycobacterium tuberculosis (Mtb) requires further investigation. We have reconstituted the leading-strand replication process of the Mtb DNA pol III holoenzyme in vitro, and investigated the physical and functional relationships between its key components. We verify the presence of an alphabeta2epsilon polymerase-clamp-exonuclease replicase complex by biochemical methods and protein-protein interaction assays in vitro and in vivo and confirm that, in addition to the polymerase activity of its alpha subunit, Mtb DNA pol III has two potential proofreading subunits; the alpha and epsilon subunits. During DNA replication, the presence of the beta2 clamp strongly promotes the polymerization of the alphabeta2epsilon replicase and reduces its exonuclease activity. Our work provides a foundation for further research on the mechanism by which the replication machinery switches between replication and proofreading and provides an experimental platform for the selection of antimicrobials targeting DNA replication in Mtb. PMID- 26822058 TI - Group A Streptococcus exploits human plasminogen for bacterial translocation across epithelial barrier via tricellular tight junctions. AB - Group A Streptococcus (GAS) is a human-specific pathogen responsible for local suppurative and life-threatening invasive systemic diseases. Interaction of GAS with human plasminogen (PLG) is a salient characteristic for promoting their systemic dissemination. In the present study, a serotype M28 strain was found predominantly localized in tricellular tight junctions of epithelial cells cultured in the presence of PLG. Several lines of evidence indicated that interaction of PLG with tricellulin, a major component of tricellular tight junctions, is crucial for bacterial localization. A site-directed mutagenesis approach revealed that lysine residues at positions 217 and 252 within the extracellular loop of tricellulin play important roles in PLG-binding activity. Additionally, we demonstrated that PLG functions as a molecular bridge between tricellulin and streptococcal surface enolase (SEN). The wild type strain efficiently translocated across the epithelial monolayer, accompanied by cleavage of transmembrane junctional proteins. In contrast, amino acid substitutions in the PLG-binding motif of SEN markedly compromised those activities. Notably, the interaction of PLG with SEN was dependent on PLG species specificity, which influenced the efficiency of bacterial penetration. Our findings provide insight into the mechanism by which GAS exploits host PLG for acceleration of bacterial invasion into deeper tissues via tricellular tight junctions. PMID- 26822059 TI - Unclonable Plasmonic Security Labels Achieved by Shadow-Mask-Lithography-Assisted Self-Assembly. AB - An unclonable plasmonic anti-counterfeiting strategy is demonstrated, which involves the use of molecule-embedded metal@silica core-shell nanoparticles as information carriers. A shadow-mask-lithography-assisted self-assembly is developed for the fabrication of the plasmonic security labels. The produced security labels show multiple sets of coding information that are highly unique, technically unreplicable, and can be robustly decoded by portable microscopes within seconds. PMID- 26822060 TI - Whole genome re-sequencing reveals genome-wide variations among parental lines of 16 mapping populations in chickpea (Cicer arietinum L.). AB - BACKGROUND: Chickpea (Cicer arietinum L.) is the second most important grain legume cultivated by resource poor farmers in South Asia and Sub-Saharan Africa. In order to harness the untapped genetic potential available for chickpea improvement, we re-sequenced 35 chickpea genotypes representing parental lines of 16 mapping populations segregating for abiotic (drought, heat, salinity), biotic stresses (Fusarium wilt, Ascochyta blight, Botrytis grey mould, Helicoverpa armigera) and nutritionally important (protein content) traits using whole genome re-sequencing approach. RESULTS: A total of 192.19 Gb data, generated on 35 genotypes of chickpea, comprising 973.13 million reads, with an average sequencing depth of ~10 X for each line. On an average 92.18 % reads from each genotype were aligned to the chickpea reference genome with 82.17 % coverage. A total of 2,058,566 unique single nucleotide polymorphisms (SNPs) and 292,588 Indels were detected while comparing with the reference chickpea genome. Highest number of SNPs were identified on the Ca4 pseudomolecule. In addition, copy number variations (CNVs) such as gene deletions and duplications were identified across the chickpea parental genotypes, which were minimum in PI 489777 (1 gene deletion) and maximum in JG 74 (1,497). A total of 164,856 line specific variations (144,888 SNPs and 19,968 Indels) with the highest percentage were identified in coding regions in ICC 1496 (21 %) followed by ICCV 97105 (12 %). Of 539 miscellaneous variations, 339, 138 and 62 were inter-chromosomal variations (CTX), intra-chromosomal variations (ITX) and inversions (INV) respectively. CONCLUSION: Genome-wide SNPs, Indels, CNVs, PAVs, and miscellaneous variations identified in different mapping populations are a valuable resource in genetic research and helpful in locating genes/genomic segments responsible for economically important traits. Further, the genome-wide variations identified in the present study can be used for developing high density SNP arrays for genetics and breeding applications. PMID- 26822061 TI - Effect of Selenium Substitution on Intersystem Crossing in pi-Conjugated Donor Acceptor-Donor Chromophores: The LUMO Matters the Most. AB - This study explores the effect of substitution of selenium (Se) for sulfur (S) on the photophysical properties of a series of pi-conjugated donor-acceptor-donor chromophores based on 4,7-bis(2-thienyl)-2,1,3-benzothiadiazole (TBT). The effect of Se substitution is studied systematically, where the substitution is in the thiophene donors only, the benzothiadiazole acceptor only, and in all of the positions. The fluorescence quantum yield decreases with an increase in Se substitution. Nanosecond-microsecond transient absorption and singlet oxygen sensitization experiments show that the effect of Se is due to an increase in the rate and efficiency of intersystem crossing with increased Se substitution. The relationship between intersystem crossing efficiency and heteroatom substitution pattern shows that the effects are largest when the heavy atom Se is in the acceptor benzothiadiazole unit. DFT calculations support the hypothesis that the effect arises because the LUMO is concentrated in the acceptor moiety, enhancing the spin-orbit coupling effect imparted by the Se atom. PMID- 26822063 TI - Allyl isothiocyanate suppresses the proteolytic activation of sterol regulatory element-binding proteins and de novo fatty acid and cholesterol synthesis. AB - Sterol regulatory element-binding proteins (SREBPs) are a family of transcription factors that regulate lipid homeostasis by controlling the expression of genes involved in fatty acid and cholesterol synthesis. In this study, we used a stable cell line that expresses a luciferase reporter gene driven by an SRE-containing fatty acid synthase promoter to identify allyl isothiocyanate (AITC), one of the major isothiocyanates in cruciferous vegetables, as a novel SREBP inactivator. We found that AITC downregulated the proteolytic processing of SREBPs and the expression of their target genes in human hepatoma Huh-7 cells. Furthermore, AITC reduced the de novo synthesis of both fatty acids and cholesterol. Our results indicate a novel physiological function of AITC in lipid metabolism regulation. PMID- 26822062 TI - Genome-wide transcriptome analysis of hypothalamus in rats with inherited stress induced arterial hypertension. AB - BACKGROUND: The hypothalamus has an important role in the onset and maintenance of hypertension and stress responses. Rats with inherited stress-induced arterial hypertension (ISIAH), reproducing the human stress-sensitive hypertensive state with predominant involvement of the neuroendocrine hypothalamic-pituitary-adrenal and sympathoadrenal axes, were used for analysis of the hypothalamus transcriptome. RESULTS: RNA-seq analysis revealed 139 genes differentially expressed in the hypothalami of hypertensive ISIAH and normotensive Wistar Albino Glaxo (WAG) rats. According to the annotation in databases, 18 of the differentially expressed genes (DEGs) were associated with arterial hypertension. The Gene Ontology (GO) functional annotation showed that these genes were related to different biological processes that may contribute to the hypertension development in the ISIAH rats. The most significantly affected processes were the following: regulation of hormone levels, immune system process, regulation of response to stimulus, blood circulation, response to stress, response to hormone stimulus, transport, metabolic processes, and endocrine system development. The most significantly affected metabolic pathways were those associated with the function of the immune system and cell adhesion molecules and the metabolism of retinol and arachidonic acid. Of the top 40 DEGs making the greatest contribution to the interstrain differences, there were 3 genes (Ephx2, Cst3 and Ltbp2) associated with hypertension that were considered to be suitable for further studies as potential targets for the stress-sensitive hypertension therapy. Seven DEGs were found to be common between hypothalamic transcriptomes of ISIAH rats and Schlager mice with established neurogenic hypertension. CONCLUSIONS: The results of this study revealed multiple DEGs and possible mechanisms specifying the hypothalamic function in the hypertensive ISIAH rats. These results provide a basis for further investigation of the signalling mechanisms that affect hypothalamic output related to stress-sensitive hypertension development. PMID- 26822064 TI - Adjunctive metformin for antipsychotic-induced hyperprolactinemia: A systematic review. AB - This systematic review examines adjunctive metformin therapy for the treatment of antipsychotic-induced hyperprolactinemia. A computerized search of databases in Chinese and the international databases in English provided three trials with a total of 325 patients including one randomized clinical trial (RCT) and two observational studies (single-group, before-after design). A meta-analysis could not be conducted. The quality of evidence ranged from "very low" to "moderate". Metformin patients had a significant decrease in serum prolactin level with a mean of 54.6MUg/l in the three trials. In the RCT, menstruation restarted in 67% of those with menstrual disturbances versus 5% in placebo. In one observational study, 91% of patients no longer had signs or symptoms of galactorrhea. In the RCT, adverse drug reactions (ADRs) occurred at similar incidence rates among metformin and placebo patients, except that no significant increases in nausea, insomnia and agitation occurred which were not associated with discontinuations. Our systematic review indicated that adjunctive metformin significantly lowered prolactin level and relieved prolactin-related symptoms in patients with antipsychotic-induced hyperprolactinemia. Future higher quality RCTs need to verify the currently available limited evidence based on three trials which suggest that adjunctive metformin may be used effectively and safely for antipsychotic-induced hyperprolactinemia. PMID- 26822065 TI - Abnormal decision-making in generalized anxiety disorder: Aversion of risk or stimulus-reinforcement impairment? AB - There is preliminary data indicating that patients with generalized anxiety disorder (GAD) show impairment on decision-making tasks requiring the appropriate representation of reinforcement value. The current study aimed to extend this literature using the passive avoidance (PA) learning task, where the participant has to learn to respond to stimuli that engender reward and avoid responding to stimuli that engender punishment. Six stimuli engendering reward and six engendering punishment are presented once per block for 10 blocks of trials. Thirty-nine medication-free patients with GAD and 29 age-, IQ and gender matched healthy comparison individuals performed the task. In addition, indexes of social functioning as assessed by the Global Assessment of Functioning (GAF) scale were obtained to allow for correlational analyzes of potential relations between cognitive and social impairments. The results revealed a Group-by-Error Type-by Block interaction; patients with GAD committed significantly more commission (passive avoidance) errors than comparison individuals in the later blocks (blocks 7,8, and 9). In addition, the extent of impairment on these blocks was associated with their functional impairment as measured by the GAF scale. These results link GAD with anomalous decision-making and indicate that a potential problem in reinforcement representation may contribute to the severity of expression of their disorder. PMID- 26822067 TI - Cherry-flavoured electronic cigarettes expose users to the inhalation irritant, benzaldehyde. AB - Many non-cigarette tobacco products, including e-cigarettes, contain various flavourings, such as fruit flavours. Although many flavourings used in e cigarettes are generally recognised as safe when used in food products, concerns have been raised about the potential inhalation toxicity of these chemicals. Benzaldehyde, which is a key ingredient in natural fruit flavours, has been shown to cause irritation of respiratory airways in animal and occupational exposure studies. Given the potential inhalation toxicity of this compound, we measured benzaldehyde in aerosol generated in a laboratory setting from flavoured e cigarettes purchased online and detected benzaldehyde in 108 out of 145 products. The highest levels of benzaldehyde were detected in cherry-flavoured products. The benzaldehyde doses inhaled with 30 puffs from flavoured e-cigarettes were often higher than doses inhaled from a conventional cigarette. Levels in cherry flavoured products were >1000 times lower than doses inhaled in the workplace. While e-cigarettes seem to be a promising harm reduction tool for smokers, findings indicate that using these products could result in repeated inhalation of benzaldehyde, with long-term users risking regular exposure to the substance. Given the uncertainty surrounding adverse health effects stemming from long-term inhalation of flavouring ingredients such as benzaldehyde, clinicians need to be aware of this emerging risk and ask their patients about use of flavoured e cigarettes. PMID- 26822066 TI - Communication Skills Training in Pediatric Oncology: Moving Beyond Role Modeling. AB - Communication is central to pediatric oncology care. Pediatric oncologists disclose life-threatening diagnoses, explain complicated treatment options, and endeavor to give honest prognoses, to maintain hope, to describe treatment complications, and to support families in difficult circumstances ranging from loss of function and fertility to treatment-related or disease-related death. However, parents, patients, and providers report substantial communication deficits. Poor communication outcomes may stem, in part, from insufficient communication skills training, overreliance on role modeling, and failure to utilize best practices. This review summarizes evidence for existing methods to enhance communication skills and calls for revitalizing communication skills training within pediatric oncology. PMID- 26822068 TI - Measuring Exocytosis Rate Using Corrected Fluorescence Recovery After Photoconversion. AB - Exocytosis plays crucial roles in regulating the distribution and function of plasma membrane (PM) and extracellular matrix proteins. However, measuring the exocytosis rate of a specific protein by conventional methods is very difficult because of exocytosis-independent trafficking such as endocytosis, which also affects membrane protein distribution. Here, we describe a novel method, corrected fluorescence recovery after photoconversion, in which exocytosis dependent and -independent trafficking events are measured simultaneously to accurately determine exocytosis rate. In this method, the protein-of-interest is tagged with Dendra2, a green-to-red photoconvertible fluorescent protein. Following the photoconversion of PM-localized Dendra2, both the recovery of the green signal and the changes in the photoconverted red signal are measured, and the rate of exocytosis is calculated from the changing rates of these two signals. PMID- 26822070 TI - Reducing emergency admissions through community based interventions. PMID- 26822069 TI - Odontogenic myxoma: a clinicopathological study in a South African population. AB - BACKGROUND: Odontogenic myxoma is a benign, locally aggressive neoplasm of the jaws. Prevalence rates range between 0.5% and 17.7% of odontogenic tumours. There are few reports in the literature on this lesion in African populations, and therefore, this study aimed to report on odontogenic myxoma in a South African population over a 40-year period. METHODS: The clinical records and orthopantomograms of 29 histopathologically diagnosed odontogenic myxoma were retrospectively analysed. Details of age, gender, ethnic origin and clinical, histological as well as radiological features were recorded. RESULTS: The ages of patients ranged from 7 to 44 years with a mean of 21.3 years. The male-to-female ratio was 1:2.6 with the majority of patients being of mixed race and Africans. Clinically, 31% complained of pain while 58.6% had a history of swelling. The majority of odongenic myxomas (62.1%) were located in the mandible with the posterior region being most commonly affected. Multilocular lesions (69.2%) were more common and were significantly larger than unilocular lesions (P < 0.05). The outline of these tumours was mostly well-defined (84.6%) with different degrees of cortication. Only one tumour caused tooth resorption, while 20 cases (76.9%) caused tooth displacement. Six tumours expanded into the maxillary sinus, and 14 tumours caused expansion of the mandible. CONCLUSIONS: Odontogenic myxomas have variable clinical, radiological and histological features. Most of these features in this population were similar to other populations. It is mandatory to use conventional radiographs along with histopathological examination to aid in arriving at an accurate diagnosis. PMID- 26822071 TI - [Asbestos and respiratory diseases]. AB - Previous occupational asbestos exposure (more rarely environmental or domestic exposure) may induce various pleural and/or pulmonary, benign or malignant diseases, sometimes with a very long latency for malignant mesothelioma (MM). Asbestos has been widely extracted and used in Western countries and in emerging or developing countries, resulting in a peak of MM incidence in France around 2020 and likely in a world pandemic of asbestos-induced diseases. These patients have mostly benign respiratory diseases (pleural plugs) but may also be diagnosed with lung cancer or malignant pleural mesothelioma, and have a global poor outcome. New therapeutic tools (targeted therapies, immunotherapy...) with first promising results are developed. However, it is crucial to obtain a full ban of asbestos use worldwide, and to do a regular follow-up of asbestos-exposed subjects, mostly if they are already diagnosed with benign respiratory diseases. Finally, new cancers (larynx and ovary) were recently added to the list of asbestos-induced tumors. PMID- 26822072 TI - Effectiveness and safety of abatacept in elderly patients with rheumatoid arthritis enrolled in the French Society of Rheumatology's ORA registry. AB - OBJECTIVE: To study the effect of age on the risk-benefit balance of abatacept in RA. METHODS: Data from the French orencia and RA registry, including a 2-year follow-up, were used to compare the effectiveness and safety of abatacept according to age. RESULTS: Among the 1017 patients, 103 were very elderly (?75 years), 215 elderly (65-74), 406 intermediate aged (50-64) and 293 very young (<50). At baseline, elderly and very elderly patients had longer disease duration, higher CRP levels and higher disease activity. These age groups showed a lower incidence of previous anti-TNF therapy and less common concomitant use of DMARDs, but a similar use of corticosteroid therapy. After adjusting for disease duration, RF/ACPA positivity, use of DMARDs or corticosteroids and previous anti TNF treatment, the EULAR response (good or moderate) and the remission rate were not significantly different between the four age groups. At 6 months, the very elderly had a significantly lower likelihood of a good response than the very young (odds ratio = 0.15, 95% CI: 0.03, 0.68). The decrease in DAS28-ESR over the 24-month follow-up period did not differ by age. Increasing age was associated with a higher rate of discontinuation for adverse events, especially severe infections (per 100 patient-years: 1.73 in very young, 4.65 in intermediates, 5.90 in elderly, 10.38 in very elderly; P < 0.001). CONCLUSION: The effectiveness of abatacept is not affected by age, but the increased rate of side effects, especially infections, in the elderly must be taken into account. PMID- 26822073 TI - The Effect of Information Communication Technology Interventions on Reducing Social Isolation in the Elderly: A Systematic Review. AB - BACKGROUND: The aging of the population is an inexorable change that challenges governments and societies in every developed country. Based on clinical and empirical data, social isolation is found to be prevalent among elderly people, and it has negative consequences on the elderly's psychological and physical health. Targeting social isolation has become a focus area for policy and practice. Evidence indicates that contemporary information and communication technologies (ICT) have the potential to prevent or reduce the social isolation of elderly people via various mechanisms. OBJECTIVE: This systematic review explored the effects of ICT interventions on reducing social isolation of the elderly. METHODS: Relevant electronic databases (PsycINFO, PubMed, MEDLINE, EBSCO, SSCI, Communication Studies: a SAGE Full-Text Collection, Communication & Mass Media Complete, Association for Computing Machinery (ACM) Digital Library, and IEEE Xplore) were systematically searched using a unified strategy to identify quantitative and qualitative studies on the effectiveness of ICT mediated social isolation interventions for elderly people published in English between 2002 and 2015. Narrative synthesis was performed to interpret the results of the identified studies, and their quality was also appraised. RESULTS: Twenty five publications were included in the review. Four of them were evaluated as rigorous research. Most studies measured the effectiveness of ICT by measuring specific dimensions rather than social isolation in general. ICT use was consistently found to affect social support, social connectedness, and social isolation in general positively. The results for loneliness were inconclusive. Even though most were positive, some studies found a nonsignificant or negative impact. More importantly, the positive effect of ICT use on social connectedness and social support seemed to be short-term and did not last for more than six months after the intervention. The results for self-esteem and control over one's life were consistent but generally nonsignificant. ICT was found to alleviate the elderly's social isolation through four mechanisms: connecting to the outside world, gaining social support, engaging in activities of interests, and boosting self-confidence. CONCLUSIONS: More well-designed studies that contain a minimum risk of research bias are needed to draw conclusions on the effectiveness of ICT interventions for elderly people in reducing their perceived social isolation as a multidimensional concept. The results of this review suggest that ICT could be an effective tool to tackle social isolation among the elderly. However, it is not suitable for every senior alike. Future research should identify who among elderly people can most benefit from ICT use in reducing social isolation. Research on other types of ICT (eg, mobile phone-based instant messaging apps) should be conducted to promote understanding and practice of ICT-based social isolation interventions for elderly people. PMID- 26822074 TI - Erythropoiesis-stimulating agent slows the progression of chronic kidney disease: a possibility of a direct action of erythropoietin. AB - BACKGROUND: Controversy exists regarding the renoprotective effect of erythropoiesis-stimulating agent (ESA) in progressive chronic kidney disease (CKD) with renal anemia. In this study, we examined whether ESA therapy has a renoprotective effect in progressive CKD. METHODS: The subjects in this retrospective observational study were 68 non-dialysis dependent CKD patients with renal anemia. We compared the progression rate (PR), defined by the slope of the linear regression line of estimated glomerular filtration rate, measured during 6 months just before and after the start of ESA therapy. We also investigated the factors affecting renoprotective efficacy of ESA therapy against the progression of CKD. RESULTS: Median (interquartile range) PR decreased significantly from 6.2 (3.7-12.7) to 4.0 (-0.3 to 7.3) mL/min/1.73 m(2)/year after the start of ESA therapy. Blood pressure levels and rate of medication with renin-angiotensin system inhibitors were comparable between the two periods. Next, we investigated the factors affecting renoprotective efficacy of ESA therapy against the progression of CKD. Thirty patients were good renal responders, defined as those with the ratio of post-/pre-PR of <0.5 and the difference of pre- minus post-PR >5.0 mL/min/1.73 m(2)/year, and 38 patients were poor renal responders who did not meet the definition of good renal responders. Multivariable logistic regression analysis showed that weekly ESA dose, but not increase in hemoglobin level, was a significant and independent determinant of the renoprotective effect of ESA. CONCLUSION: ESA therapy slows the progression of CKD and part of the effect might be attributed to the direct renoprotective action of ESA. PMID- 26822075 TI - Increased body mass index as a risk factor in localized prostate cancer treated by radical prostatectomy. AB - BACKGROUND: The association between obesity and aggressive forms of prostate cancer is controversial. We compared preoperative body mass index (BMI) and prostate-specific antigen (PSA) levels as predictive risk factors for increased prostate weight and disease aggressiveness. MATERIALS AND METHODS: This retrospective review of 464 patients with localized prostate cancer who underwent radical prostatectomy between March 1999 and October 2006 examined relationships among clinicopathological variables (BMI, preoperative serum PSA, biopsy and pathologic Gleason score [GS], and whole prostate weight) using linear and multinomial logistic regression analysis. We used multivariate regression modeling adjusting for age, year of surgery, PSA or BMI, pathologic stage, and GS. RESULTS: Median age of patients (51% cT1c, 69% pT2) was 61 years (41-76), mean BMI 26.50kg/m(2) (standard deviation = 4.82), mean PSA 6.8ng/ml (0.67-27.2), median prostate weight 51g (12-200), median biopsy GS 6 (3-9), and median pathologic GS 7 (4-10). GS was upgraded in 227 patients (49%) from median GS 6 to 7 (P<0.00001). Mean prostate weight was 47+/-13.7g for BMI<25kg/m(2) (n = 170), 47+/-15g for BMI 25 to 30kg/m(2) (n = 224), and 59+/-26g for BMI>30kg/m(2) (n = 69) (P<0.00184). Mean prostate weight was significantly higher for BMI>30 than BMI<25 (47+/-13g vs. 59+/-25g, P<0.00015). Mean PSA was significantly higher for BMI>30 than for all other patients combined (8.56 [95% CI: 6.94-10.18] vs. 8.34 [7.23-9.45]; P = 0.001). PSA was positively associated with high biopsy GS for BMI>=25 (P = 0.048) and BMI>=30 (P = 0.009) but not for BMI<=25 (P = 0.151). BMI>=30 was associated with higher pT stage (odd ratio = 1.279 [1.5-1.56]; P = 0.015). In multivariate analyses, higher BMI was associated with higher prostate weight (P = 0.036) and pT stage (P = 0.008), and higher PSA with higher biopsy GS (P = 0.002). Neither BMI nor PSA was associated with GS upgrading. CONCLUSIONS: Higher BMI was associated with higher prostate weight and PSA, as well as with higher pT stage and pathologic GS in men undergoing radical prostatectomy, providing further evidence that obese men are more likely to have aggressive cancer. BMI thus constitutes an additional risk factor besides PSA. PMID- 26822076 TI - Advanced imaging techniques in genitourinary cancers. PMID- 26822077 TI - Baseline tumor volume in assessing prognosis of patients with intermediate-risk synchronous metastatic renal cell carcinoma. AB - OBJECTIVE: To analyze if prediction of survival for patients with synchronous metastatic renal cell cancer (mRCC) could be further refined by baseline volume of the primary tumor, the metastases, or the remaining volume after surgery; this study was performed because survival expectancies of patients with intermediate risk mRCC vary substantially. MATERIAL AND METHODS: The predictive value of the different volumes on overall survival (OS) was analyzed retrospectively in patients with intermediate Memorial Sloan-Kettering Cancer Center (MSKCC) risk profile and <=3 International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) factors, who received sunitinib in our institute. Tumor volumes were calculated on segmented computed tomography using in-house developed software. A multivariate analysis was performed including number of metastatic sites and baseline tumor burden (TB). RESULTS: A total of 68 patients were included. Median OS for patients without cytoreductive nephrectomy (CN) was 6 months (95% CI: 3.0 8.9mo) vs. 31 months (95% CI: 23.1-38.8mo) for those with CN, respectively. More second-line treatment was given after CN (49% vs. 17%, P = 0.125). There was no correlation between tumor volume and TB measured by Response Evaluation Criteria in Solid Tumors. Of all included clinical and volumetric parameters, remaining volume after CN, CN status and 2 vs. 3 IMDC factors were significantly correlated with OS. In the Cox regression analysis, CN was the only remaining significant parameter (P = 0.003). CONCLUSIONS: None of the baseline volumetric parameters is an independent prognostic factor in patients with intermediate MSKCC risk mRCC with<=3 IMDC factors receiving sunitinib. Only CN status correlated significantly with prognosis. None of the baseline volumes nor TB by Response Evaluation Criteria in Solid Tumors was associated with CN status, suggesting that extent of disease had no significant influence on the decision to perform surgery. PMID- 26822078 TI - Overweight or not-Prostate-specific antigen levels reflect a continuum of risk influenced by other factors. PMID- 26822080 TI - Promising new therapies for the treatment of hypercholesterolemia. AB - INTRODUCTION: Statins are currently the most commonly used agents for treatment of hypercholesterolemia in patients with atherosclerotic cardiovascular disease. However, some patients on statins do not achieve their treatment goals or are intolerant to statins. Therefore, new therapies for treatment of hypercholesterolemia are under investigation. AREAS COVERED: This article reviews the new emerging medications for the treatment of hypercholesterolemia and discusses their efficacy and safety profile based on literature searches that included human studies published on PubMed and reported clinical trials. EXPERT OPINION: Inhibition of the PCSK9 protein by monoclonal antibodies results in a dramatic 40%-60% lowering of serum low-density lipoprotein cholesterol (LDL-C). This is in addition to LDL-C lowering achieved by statins. Multiple clinical studies have demonstrated the high selectivity of these antibodies for the PCSK9 pathway and their long-term safety and efficacy. Alirocumab and evolocumab have been approved by the FDA for the treatment of patients with heterozygous familial hypercholesterolemia and patients with clinical atherosclerotic cardiovascular disease) who do not achieve their LDL-C target on maximal tolerated statin treatment and dietary modification. In addition, evolocumab has been approved by the FDA for homozygous familial hypercholesterolemia. However, the long-term efficacy and safety of PCSK9 inhibitors are unknown. PMID- 26822079 TI - A Phytophthora infestans RXLR effector targets plant PP1c isoforms that promote late blight disease. AB - Plant pathogens deliver effectors to alter host processes. Knowledge of how effectors target and manipulate host proteins is critical to understand crop disease. Here, we show that in planta expression of the RXLR effector Pi04314 enhances leaf colonization by Phytophthora infestans via activity in the host nucleus and attenuates induction of jasmonic and salicylic acid-responsive genes. Pi04314 interacts with three host protein phosphatase 1 catalytic (PP1c) isoforms, causing their re-localization from the nucleolus to the nucleoplasm. Re localization of PP1c-1 also occurs during infection and is dependent on an R/KVxF motif in the effector. Silencing the PP1c isoforms or overexpression of a phosphatase-dead PP1c-1 mutant attenuates infection, demonstrating that host PP1c activity is required for disease. Moreover, expression of PP1c-1mut abolishes enhanced leaf colonization mediated by in planta Pi04314 expression. We argue that PP1c isoforms are susceptibility factors forming holoenzymes with Pi04314 to promote late blight disease. PMID- 26822083 TI - PGC-1alpha Coordinates Mitochondrial Respiratory Capacity and Muscular Fatty Acid Uptake via Regulation of VEGF-B. AB - Vascular endothelial growth factor (VEGF) B belongs to the VEGF family, but in contrast to VEGF-A, VEGF-B does not regulate blood vessel growth. Instead, VEGF-B controls endothelial fatty acid (FA) uptake and was identified as a target for the treatment of type 2 diabetes. The regulatory mechanisms controlling Vegfb expression have remained unidentified. We show that peroxisome proliferator activated receptor gamma coactivator 1alpha (PGC-1alpha) together with estrogen related receptor alpha (ERR-alpha) regulates expression of Vegfb Mice overexpressing PGC-1alpha under the muscle creatine kinase promoter (MPGC 1alphaTG mice) displayed increased Vegfb expression, and this was accompanied by increased muscular lipid accumulation. Ablation of Vegfb in MPGC-1alphaTG mice fed a high-fat diet (HFD) normalized glucose intolerance, insulin resistance, and dyslipidemia. We suggest that VEGF-B is the missing link between PGC-1alpha overexpression and the development of the diabetes-like phenotype in HFD-fed MPGC 1alphaTG mice. The findings identify Vegfb as a novel gene regulated by the PGC 1alpha/ERR-alpha signaling pathway. Furthermore, the study highlights the role of PGC-1alpha as a master metabolic sensor that by regulating the expression levels of Vegfa and Vegfb coordinates blood vessel growth and FA uptake with mitochondrial FA oxidation. PMID- 26822081 TI - Myeloid Deletion of alpha1AMPK Exacerbates Atherosclerosis in LDL Receptor Knockout (LDLRKO) Mice. AB - Macrophage inflammation marks all stages of atherogenesis, and AMPK is a regulator of macrophage inflammation. We therefore generated myeloid alpha1AMPK knockout (MAKO) mice on the LDL receptor knockout (LDLRKO) background to investigate whether myeloid deletion of alpha1AMPK exacerbates atherosclerosis. When fed an atherogenic diet, MAKO/LDLRKO mice displayed exacerbated atherosclerosis compared with LDLRKO mice. To determine the underlying pathophysiological pathways, we characterized macrophage inflammation/chemotaxis and lipid/cholesterol metabolism in MAKO/LDLRKO mice. Myeloid deletion of alpha1AMPK increased macrophage inflammatory gene expression and enhanced macrophage migration and adhesion to endothelial cells. Remarkably, MAKO/LDLRKO mice also displayed higher composition of circulating chemotaxically active Ly 6C(high) monocytes, enhanced atherosclerotic plaque chemokine expression, and monocyte recruitment into plaques, leading to increased atherosclerotic plaque macrophage content and inflammation. MAKO/LDLRKO mice also exhibited higher plasma LDL and VLDL cholesterol content, increased circulating apolipoprotein B (apoB) levels, and higher liver apoB expression. We conclude that macrophage alpha1AMPK deficiency promotes atherogenesis in LDLRKO mice and is associated with enhanced macrophage inflammation and hypercholesterolemia and that macrophage alpha1AMPK may serve as a therapeutic target for prevention and treatment of atherosclerosis. PMID- 26822085 TI - Unacylated Ghrelin Reduces Skeletal Muscle Reactive Oxygen Species Generation and Inflammation and Prevents High-Fat Diet-Induced Hyperglycemia and Whole-Body Insulin Resistance in Rodents. AB - Excess reactive oxygen species (ROS) generation and inflammation may contribute to obesity-associated skeletal muscle insulin resistance. Ghrelin is a gastric hormone whose unacylated form (UnAG) is associated with whole-body insulin sensitivity in humans and may reduce oxidative stress in nonmuscle cells in vitro. We hypothesized that UnAG 1) lowers muscle ROS production and inflammation and enhances tissue insulin action in lean rats and 2) prevents muscle metabolic alterations and normalizes insulin resistance and hyperglycemia in high-fat diet (HFD)-induced obesity. In 12-week-old lean rats, UnAG (4-day, twice-daily subcutaneous 200-ug injections) reduced gastrocnemius mitochondrial ROS generation and inflammatory cytokines while enhancing AKT-dependent signaling and insulin-stimulated glucose uptake. In HFD-treated mice, chronic UnAG overexpression prevented obesity-associated hyperglycemia and whole-body insulin resistance (insulin tolerance test) as well as muscle oxidative stress, inflammation, and altered insulin signaling. In myotubes, UnAG consistently lowered mitochondrial ROS production and enhanced insulin signaling, whereas UnAG effects were prevented by small interfering RNA-mediated silencing of the autophagy mediator ATG5. Thus, UnAG lowers mitochondrial ROS production and inflammation while enhancing insulin action in rodent skeletal muscle. In HFD induced obesity, these effects prevent hyperglycemia and insulin resistance. Stimulated muscle autophagy could contribute to UnAG activities. These findings support UnAG as a therapeutic strategy for obesity-associated metabolic alterations. PMID- 26822084 TI - Deficiency in Apoptosis-Inducing Factor Recapitulates Chronic Kidney Disease via Aberrant Mitochondrial Homeostasis. AB - Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein with dual roles in redox signaling and programmed cell death. Deficiency in AIF is known to result in defective oxidative phosphorylation (OXPHOS), via loss of complex I activity and assembly in other tissues. Because the kidney relies on OXPHOS for metabolic homeostasis, we hypothesized that a decrease in AIF would result in chronic kidney disease (CKD). Here, we report that partial knockdown of Aif in mice recapitulates many features of CKD, in association with a compensatory increase in the mitochondrial ATP pool via a shift toward mitochondrial fusion, excess mitochondrial reactive oxygen species production, and Nox4 upregulation. However, despite a 50% lower AIF protein content in the kidney cortex, there was no loss of complex I activity or assembly. When diabetes was superimposed onto Aif knockdown, there were extensive changes in mitochondrial function and networking, which augmented the renal lesion. Studies in patients with diabetic nephropathy showed a decrease in AIF within the renal tubular compartment and lower AIFM1 renal cortical gene expression, which correlated with declining glomerular filtration rate. Lentiviral overexpression of Aif1m rescued glucose induced disruption of mitochondrial respiration in human primary proximal tubule cells. These studies demonstrate that AIF deficiency is a risk factor for the development of diabetic kidney disease. PMID- 26822082 TI - HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 Haplotype Protects Autoantibody-Positive Relatives From Type 1 Diabetes Throughout the Stages of Disease Progression. AB - The HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype is linked to protection from the development of type 1 diabetes (T1D). However, it is not known at which stages in the natural history of T1D development this haplotype affords protection. We examined a cohort of 3,358 autoantibody-positive relatives of T1D patients in the Pathway to Prevention (PTP) Study of the Type 1 Diabetes TrialNet. The PTP study examines risk factors for T1D and disease progression in relatives. HLA typing revealed that 155 relatives carried this protective haplotype. A comparison with 60 autoantibody-negative relatives suggested protection from autoantibody development. Moreover, the relatives with DRB1*15:01 DQA1*01:02-DQB1*06:02 less frequently expressed autoantibodies associated with higher T1D risk, were less likely to have multiple autoantibodies at baseline, and rarely converted from single to multiple autoantibody positivity on follow up. These relatives also had lower frequencies of metabolic abnormalities at baseline and exhibited no overall metabolic worsening on follow-up. Ultimately, they had a very low 5-year cumulative incidence of T1D. In conclusion, the protective influence of DRB1*15:01-DQA1*01:02-DQB1*06:02 spans from autoantibody development through all stages of progression, and relatives with this allele only rarely develop T1D. PMID- 26822086 TI - Plasma Metabonomic Profiling of Diabetic Retinopathy. AB - Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the leading cause of visual impairment in working-age adults. Patients with diabetes often develop DR despite appropriate control of systemic risk factors, suggesting the involvement of other pathogenic factors. We hypothesize that the plasma metabolic signature of DR is distinct and resolvable from that of diabetes alone. A nested population-based case-control metabonomic study was first performed on 40 DR cases and 40 control subjects with diabetes using gas chromatography-mass spectrometry. Eleven metabolites were found to be correlated with DR, and the majority were robust when adjusted for metabolic risk factors and confounding kidney disease. The metabolite markers 2-deoxyribonic acid; 3,4-dihydroxybutyric acid; erythritol; gluconic acid; and ribose were validated in an independent sample set with 40 DR cases, 40 control subjects with diabetes, and 40 individuals without diabetes. DR cases and control subjects with diabetes were matched by HbA1c in the validation set. Activation of the pentose phosphate pathway was identified from the list of DR metabolite markers. The identification of novel metabolite markers for DR provides insights into potential new pathogenic pathways for this microvascular complication and holds translational value in DR risk stratification and the development of new therapeutic measures. PMID- 26822087 TI - Euglycemia Restoration by Central Leptin in Type 1 Diabetes Requires STAT3 Signaling but Not Fast-Acting Neurotransmitter Release. AB - Central leptin action is sufficient to restore euglycemia in insulinopenic type 1 diabetes (T1D); however, the underlying mechanism remains poorly understood. To examine the role of intracellular signal transducer and activator of transcription 3 (STAT3) pathways, we used LepRs/s mice with disrupted leptin phosphorylated STAT3 signaling to test the effect of central leptin on euglycemia restoration. These mice developed streptozocin-induced T1D, which was surprisingly not associated with hyperglucagonemia, a typical manifestation in T1D. Further, leptin action on euglycemia restoration was abrogated in these mice, which was associated with refractory hypercorticosteronemia. To examine the role of fast-acting neurotransmitters glutamate and gamma-aminobutyric acid (GABA), two major neurotransmitters in the brain, from leptin receptor (LepR) neurons, we used mice with disrupted release of glutamate, GABA, or both from LepR neurons. Surprisingly, all mice responded normally to leptin-mediated euglycemia restoration, which was associated with expected correction from hyperglucagonemia and hyperphagia. In contrast, mice with loss of glutamate and GABA appeared to develop an additive obesity effect over those with loss of single neurotransmitter release. Thus, our study reveals that STAT3 signaling, but not fast-acting neurotransmitter release, is required for leptin action on euglycemia restoration and that hyperglucagonemia is not required for T1D. PMID- 26822088 TI - Sorcin Links Pancreatic beta-Cell Lipotoxicity to ER Ca2+ Stores. AB - Preserving beta-cell function during the development of obesity and insulin resistance would limit the worldwide epidemic of type 2 diabetes. Endoplasmic reticulum (ER) calcium (Ca(2+)) depletion induced by saturated free fatty acids and cytokines causes beta-cell ER stress and apoptosis, but the molecular mechanisms behind these phenomena are still poorly understood. Here, we demonstrate that palmitate-induced sorcin downregulation and subsequent increases in glucose-6-phosphatase catalytic subunit-2 (G6PC2) levels contribute to lipotoxicity. Sorcin is a calcium sensor protein involved in maintaining ER Ca(2+) by inhibiting ryanodine receptor activity and playing a role in terminating Ca(2+)-induced Ca(2+) release. G6PC2, a genome-wide association study gene associated with fasting blood glucose, is a negative regulator of glucose stimulated insulin secretion (GSIS). High-fat feeding in mice and chronic exposure of human islets to palmitate decreases endogenous sorcin expression while levels of G6PC2 mRNA increase. Sorcin-null mice are glucose intolerant, with markedly impaired GSIS and increased expression of G6pc2 Under high-fat diet, mice overexpressing sorcin in the beta-cell display improved glucose tolerance, fasting blood glucose, and GSIS, whereas G6PC2 levels are decreased and cytosolic and ER Ca(2+) are increased in transgenic islets. Sorcin may thus provide a target for intervention in type 2 diabetes. PMID- 26822089 TI - Inhibition of miR-200c Restores Endothelial Function in Diabetic Mice Through Suppression of COX-2. AB - Endothelial dysfunction plays a crucial role in the development of diabetic vasculopathy. Our initial quantitative PCR results showed an increased miR-200c expression in arteries from diabetic mice and patients with diabetes. However, whether miR-200c is involved in diabetic endothelial dysfunction is unknown. Overexpression of miR-200c impaired endothelium-dependent relaxations (EDRs) in nondiabetic mouse aortas, whereas suppression of miR-200c by anti-miR-200c enhanced EDRs in diabetic db/db mice. miR-200c suppressed ZEB1 expression, and ZEB1 overexpression ameliorated endothelial dysfunction induced by miR-200c or associated with diabetes. More importantly, overexpression of anti-miR-200c or ZEB1 in vivo attenuated miR-200c expression and improved EDRs in db/db mice. Mechanistic study with the use of COX-2(-/-) mice revealed that COX-2 mediated miR-200c-induced endothelial dysfunction and that miR-200c upregulated COX-2 expression in endothelial cells through suppression of ZEB1 and increased production of prostaglandin E2, which also reduced EDR. This study demonstrates for the first time to our knowledge that miR-200c is a new mediator of diabetic endothelial dysfunction and inhibition of miR-200c rescues EDRs in diabetic mice. These new findings suggest the potential usefulness of miR-200c as the target for drug intervention against diabetic vascular complications. PMID- 26822090 TI - Disulfide Mispairing During Proinsulin Folding in the Endoplasmic Reticulum. AB - Proinsulin folding within the endoplasmic reticulum (ER) remains incompletely understood, but it is clear that in mutant INS gene-induced diabetes of youth (MIDY), progression of the (three) native disulfide bonds of proinsulin becomes derailed, causing insulin deficiency, beta-cell ER stress, and onset of diabetes. Herein, we have undertaken a molecular dissection of proinsulin disulfide bond formation, using bioengineered proinsulins that can form only two (or even only one) of the native proinsulin disulfide bonds. In the absence of preexisting proinsulin disulfide pairing, Cys(B19)-Cys(A20) (a major determinant of ER stress response activation and proinsulin stability) preferentially initiates B-A chain disulfide bond formation, whereas Cys(B7)-Cys(A7) can initiate only under oxidizing conditions beyond that existing within the ER of beta-cells. Interestingly, formation of these two "interchain" disulfide bonds demonstrates cooperativity, and together, they are sufficient to confer intracellular transport competence to proinsulin. The three most common proinsulin disulfide mispairings in the ER appear to involve Cys(A11)-Cys(A20), Cys(A7)-Cys(A20), and Cys(B19)-Cys(A11), each disrupting the critical Cys(B19)-Cys(A20) pairing. MIDY mutations inhibit Cys(B19)-Cys(A20) formation, but treatment to force oxidation of this disulfide bond improves folding and results in a small but detectable increase of proinsulin export. These data suggest possible therapeutic avenues to ameliorate ER stress and diabetes. PMID- 26822091 TI - Intact Regulation of the AMPK Signaling Network in Response to Exercise and Insulin in Skeletal Muscle of Male Patients With Type 2 Diabetes: Illumination of AMPK Activation in Recovery From Exercise. AB - Current evidence on exercise-mediated AMPK regulation in skeletal muscle of patients with type 2 diabetes (T2D) is inconclusive. This may relate to inadequate segregation of trimeric complexes in the investigation of AMPK activity. We examined the regulation of AMPK and downstream targets ACC-beta, TBC1D1, and TBC1D4 in muscle biopsy specimens obtained from 13 overweight/obese patients with T2D and 14 weight-matched male control subjects before, immediately after, and 3 h after exercise. Exercise increased AMPK alpha2beta2gamma3 activity and phosphorylation of ACCbeta Ser(221), TBC1D1 Ser(237)/Thr(596), and TBC1D4 Ser(704) Conversely, exercise decreased AMPK alpha1beta2gamma1 activity and TBC1D4 Ser(318)/Thr(642) phosphorylation. Interestingly, compared with preexercise, 3 h into exercise recovery, AMPK alpha2beta2gamma1 and alpha1beta2gamma1 activity were increased concomitant with increased TBC1D4 Ser(318)/Ser(341)/Ser(704) phosphorylation. No differences in these responses were observed between patients with T2D and control subjects. Subjects were also studied by euglycemic-hyperinsulinemic clamps performed at rest and 3 h after exercise. We found no evidence for insulin to regulate AMPK activity. Thus, AMPK signaling is not compromised in muscle of patients with T2D during exercise and insulin stimulation. Our results reveal a hitherto unrecognized activation of specific AMPK complexes in exercise recovery. We hypothesize that the differential regulation of AMPK complexes plays an important role for muscle metabolism and adaptations to exercise. PMID- 26822092 TI - Diabetes-Associated Variation in TCF7L2 Is Not Associated With Hepatic or Extrahepatic Insulin Resistance. AB - A common genetic variation in TCF7L2 is associated with type 2 diabetes. However, the mechanism by which this occurs remains elusive. In addition to affecting insulin secretion, genetic variation at the TCF7L2 locus may alter insulin action or directly modify hepatic glucose metabolism. We sought to determine whether the diabetes-associated variant in this locus (the T allele of rs7903146) increases fasting endogenous glucose production (EGP), and impairs insulin-induced suppression of EGP and insulin-stimulated glucose disappearance. To address this, we studied individuals who were either homozygous for the diabetes-associated allele (TT) at rs7903146 or were homozygous for the protective allele (CC). Subjects were matched for other anthropometric characteristics and were studied using a euglycemic clamp. EGP and glucose uptake were measured using the tracer dilution technique, and the relative contribution of gluconeogenesis to EGP was quantitated using deuterated water corrected for transaldolase exchange. We report that the diabetes-associated variation in TCF7L2 did not associate with fasting EGP, insulin-induced suppression of EGP, and insulin-induced stimulation of glucose uptake. There was no association with the contribution of gluconeogenesis and glycogenolysis to EGP. These data indicate that genetic variation at TCF7L2 does not predispose an individual to type 2 diabetes by altering either hepatic or extrahepatic insulin action. PMID- 26822093 TI - An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas. AB - The lymphatic system is crucial for efficient immune surveillance and for the maintenance of a physiological pressure in the interstitial space. Even so, almost no information is available concerning the lymph drainage of the islets of Langerhans in the human pancreas. Immunohistochemical staining allowed us to distinguish lymphatic capillaries from blood capillaries. Almost no lymphatic capillaries were found within the islets in pancreatic biopsy specimens from subjects without diabetes or from subjects with type 1 or type 2 diabetes. Lymphatic capillaries were, however, found at the islet-exocrine interface, frequently located along blood capillaries and other fibrotic structures within or close to the islet capsule. Lymphatic capillaries were regularly found in the exocrine pancreas, with small lymphatic vessels located close to and around acini. Larger collecting lymphatic vessels were located in fibrotic septa between the exocrine lobules and adjacent to the ductal system of the pancreas. In summary, we report a pronounced deficiency of lymphatic capillaries in human islets, a finding with implications for immune surveillance and the regulation of interstitial fluid transport in the endocrine pancreas as well as for the pathophysiology of both type 1 and type 2 diabetes. PMID- 26822094 TI - Stability Study and Kinetic Monitoring of Cefquinome Sulfate Using Cyclodextrin Based Ion-Selective Electrode: Application to Biological Samples. AB - Two novel cefquinome sulfate (CFQ)-selective electrodes were performed with dibutyl sebacate as a plasticizer using a polymeric matrix of polyvinyl chloride. Sensor 1 was prepared using sodium tetraphenylborate as a cation exchanger without incorporation of ionophore, whereas 2-hydroxy propyl beta-cyclodextrin was used as ionophore in sensor 2. A stable, reliable, and linear response was obtained in concentration ranges 3.2 * 10(-5) to 1 * 10(-2) mol/L and 1 * 10(-5) to 1 * 10(-2) mol/L for sensors 1 and 2, respectively. Both sensors could be sufficiently applied for quantitative determination of CFQ in the presence of degradation products either in bulk powder or in pharmaceutical formulations. Sensor 2 provided better selectivity and sensitivity, wider linearity range, and higher performance. Therefore it was used successfully for accurate determination of CFQ in biological fluids such as spiked plasma and milk samples. Furthermore, an online kinetic study was applied to the CFQ alkaline degradation process to estimate the reaction rate and half-life with feasible real-time monitoring. The developed sensors were found to be fast, accurate, sensitive, and precise compared with the manufacturer's reversed-phase chromatographic method. PMID- 26822095 TI - Insights into the formation mechanism of chloropropanol fatty acid esters under laboratory-scale deodorization conditions. AB - Chloropropanol fatty acid esters (CPFAEs) are well-known contaminants in refined oils and fats, and several research groups have studied their formation. However, the results obtained in these studies were not satisfactory because the CPFAEs were not analyzed comprehensively. Thus, in the present study, a comprehensive analysis was performed to obtain new details about CPFAE formation. Each lipid (monopalmitin, dipalmitin, tripalmitin, monoolein, diolein, triolein, and crude palm oil) was heated at 250 degrees C for 90 min, and the CPFAEs were analyzed using supercritical fluid chromatography/tandem mass spectrometry. It was found that CP fatty acid monoesters were formed from monoacylglycerols and diacylglycerols after heating in the presence of a chlorine compound. In addition, CP fatty acid diesters were formed from diacylglycerols and triacylglycerols under the same conditions. In the case of crude palm oil, only CP fatty acid diesters were formed. Therefore, these results indicated that CPFAEs in refined palm oil were formed mainly from triacylglycerols. PMID- 26822096 TI - Addendum to Abstracts presented at the 14th International Congress on Amino Acids, Peptides and Proteins. PMID- 26822097 TI - Proteome profiling reveals tissue-specific protein expression in male and female accessory glands of the silkworm, Bombyx mori. AB - Male accessory gland (MAG) and female accessory gland (FAG) of the reproductive system are, respectively, responsible for producing seminal proteins and adhesive proteins during copulation and ovulation. Seminal proteins are ejaculated to female along with sperms, whereas adhesive proteins are excreted along with eggs. Proteins from the male and female reproductive organs are usually indicative of rapid adaptive evolution. Understanding the reproductive isolation and species divergence requires identifying reproduction-related proteins from many different species. Here, we present our proteomic analyses of male and female accessory glands of the silkworm, Bombyx mori. Using LC/MS-MS, we identified 2133 MAG proteins and 1872 FAG proteins. In total, 652 proteins were significant more abundant in the MAG than in the FAG, including growth factors, odorant-binding proteins, enzymes, and proteins of unknown function. Growth factors and odorant binding proteins are potential signaling molecules, whereas most of proteins of unknown function were found to be Lepidoptera-specific proteins with high evolutionary rates. Microarray experiments and semi-quantitative RT-PCR validated that MAG-specific proteins were expressed exclusively in male moths. Totally, 192 proteins were considered as FAG-specific proteins, including protease inhibitors, enzymes, and other proteins. Protease inhibitors were found to be the most abundant FAG-specific proteins, which may protect eggs from infection by inhibiting pathogen-derived proteases. These results provide comprehensive insights into copulation and oviposition. Moreover, the newly identified Lepidoptera-specific MAG proteins provide useful data for future research on the evolution of reproductive proteins in insects. PMID- 26822098 TI - MTD: a mammalian transcriptomic database to explore gene expression and regulation. AB - A systematic transcriptome survey is essential for the characterization and comprehension of the molecular basis underlying phenotypic variations. Recently developed RNA-seq methodology has facilitated efficient data acquisition and information mining of transcriptomes in multiple tissues/cell lines. Current mammalian transcriptomic databases are either tissue-specific or species specific, and they lack in-depth comparative features across tissues and species. Here, we present a mammalian transcriptomic database (MTD) that is focused on mammalian transcriptomes, and the current version contains data from humans, mice, rats and pigs. Regarding the core features, the MTD browses genes based on their neighboring genomic coordinates or joint KEGG pathway and provides expression information on exons, transcripts and genes by integrating them into a genome browser. We developed a novel nomenclature for each transcript that considers its genomic position and transcriptional features. The MTD allows a flexible search of genes or isoforms with user-defined transcriptional characteristics and provides both table-based descriptions and associated visualizations. To elucidate the dynamics of gene expression regulation, the MTD also enables comparative transcriptomic analysis in both intraspecies and interspecies manner. The MTD thus constitutes a valuable resource for transcriptomic and evolutionary studies. The MTD is freely accessible at http://mtd.cbi.ac.cn. PMID- 26822099 TI - Computational methods to identify metabolic sub-networks based on metabolomic profiles. AB - Untargeted metabolomics makes it possible to identify compounds that undergo significant changes in concentration in different experimental conditions. The resulting metabolomic profile characterizes the perturbation concerned, but does not explain the underlying biochemical mechanisms. Bioinformatics methods make it possible to interpret results in light of the whole metabolism. This knowledge is modelled into a network, which can be mined using algorithms that originate in graph theory. These algorithms can extract sub-networks related to the compounds identified. Several attempts have been made to adapt them to obtain more biologically meaningful results. However, there is still no consensus on this kind of analysis of metabolic networks. This review presents the main graph approaches used to interpret metabolomic data using metabolic networks. Their advantages and drawbacks are discussed, and the impacts of their parameters are emphasized. We also provide some guidelines for relevant sub-network extraction and also suggest a range of applications for most methods. PMID- 26822100 TI - Double-masked, randomized, placebo-controlled study to evaluate the efficacy and tolerability of intranasal K305 (3% tetracaine plus 0.05% oxymetazoline) in anesthetizing maxillary teeth. AB - BACKGROUND: The authors compared the local anesthetic efficacy and safety of an intranasally administered formulation of tetracaine and oxymetazoline (K305) with placebo in adult participants undergoing single dental restorative procedures in teeth nos. 4 through 13. METHODS: The authors screened and allocated 150 participants in a double-masked, randomized fashion to either K305 or placebo nasal spray. The authors delivered the study drug as two 0.2-milliliter sprays separated by 4 minutes inside the nostril on the side ipsilateral to the tooth being treated. The authors administered a third 0.2-mL spray, if necessary, and administered 4% articaine with 1:200,000 epinephrine by means of injection if anesthesia was inadequate. Safety evaluations included participant reports of adverse events, vital signs, and alcohol sniff tests during the 2-hour study period and at a 1-day follow-up visit. The primary efficacy end point was anesthetic success defined as the completion of the dental procedure without the need for rescue injectable local anesthetic. The authors evaluated differences in success rates observed between K305 and placebo by using a 1-sided Fisher exact test. RESULTS: The overall success rates were 88.0% (95% confidence interval, 80.0-93.6) and 28% (95% confidence interval, 16.2-42.5) for K305 and placebo, respectively (P < .0001). The most frequent adverse effects in the K305 group were rhinorrhea (57.0%) and nasal congestion (26.0%). No serious adverse events occurred during this study. CONCLUSIONS: K305 was effective and well tolerated during restorative procedures in adult participants. PRACTICAL IMPLICATIONS: K305 provides a needleless alternative for obtaining maxillary pulpal anesthesia on premolars, canines, and incisors. PMID- 26822101 TI - Conference summary: Navigating the Sea of Genomic Data, October 28-29, 2015. AB - BACKGROUND: The rapid pace of biomedical discoveries in the past few years has resulted in substantial advances in our ability to diagnose, treat, and prevent a wide variety of diseases. The sequencing of the human genome offered the possibility of understanding the etiology, pathogenesis, and risk of developing disease from a genetic perspective and has resulted, for example, in the development of genomic-based diagnostic or risk-assessment tests for a number of medical and dental conditions. To assess the scientific evidence underlying such tests and determine whether they may be useful in clinical practice, practitioners need to have a basic understanding of the state-of-the-science of genomics and genetic testing. OBJECTIVE: To assist practitioners in understanding the science of genomics, the American Dental Association and the Task Force on Design and Analysis in Oral Health Research co-sponsored a landmark conference, Navigating the Sea of Genomic Data, held October 28-29, 2015, at the American Dental Association headquarters building in Chicago, IL. The purpose of this conference was to review the basics of genomic science, promote sound design and analysis of genomic studies of oral diseases, and provide a basis or "framework" to guide practitioners in assessing new development in genomics and genetic tests for oral diseases. OVERVIEW: Presentations at this conference were made by 9 world-renowned scientists who discussed a wide range of topics involving genomic science, genetic testing for rare mendelian single gene disorders, and genetic testing for assessing the risk of experiencing common complex diseases. This article summarizes the key points and concepts presented by the speakers. PRACTICAL IMPLICATIONS: It is essential for oral health care professionals to have a fundamental understanding of genomic science so that they can evaluate new advances in this field and the use of genetic testing for the benefit of their patients. PMID- 26822102 TI - Erythema Ab Igne in Three Girls with Anorexia Nervosa. AB - We present three girls with the eating disorder anorexia nervosa (AN) presenting with erythema ab igne (EAI), a benign, reticular, erythematous dermatosis caused by repeated prolonged skin exposure to mild heat. AN has been associated with abnormal peripheral vascular response to cold, vasoconstriction of the limbs, low hand blood flow, exaggerated response to cold stimuli, subnormal core temperature, and a general feeling of cold that may encourage prolonged heat exposure and induce EAI. PMID- 26822104 TI - The Bond Order of C2 from a Strictly N-Representable Natural Orbital Energy Functional Perspective. AB - The bond order of the ground electronic state of the carbon dimer has been analyzed in the light of natural orbital functional theory calculations carried out with an approximate, albeit strictly N-representable, energy functional. Three distinct solutions have been found from the Euler equations of the minimization of the energy functional with respect to the natural orbitals and their occupation numbers, which expand upon increasing values of the internuclear coordinate. In the close vicinity of the minimum energy region, two of the solutions compete around a discontinuity point. The former, corresponding to the absolute minimum energy, features two valence natural orbitals of each of the following symmetries, sigma, sigma*, pi and pi*, and has three bonding interactions and one antibonding interaction, which is very suggestive of a bond order large than two but smaller than three. The latter, features one sigma sigma* linked pair of natural orbitals and three degenerate pseudo-bonding like orbitals, paired each with one triply degenerate pseudo-antibonding orbital, which points to a bond order larger than three. When correlation effects, other than Hartree-Fock for example, between the paired natural orbitals are accounted for, this second solution vanishes yielding a smooth continuous dissociation curve. Comparison of the vibrational energies and electron ionization energies, calculated on this curve, with their corresponding experimental marks, lend further support to a bond order for C2 intermediate between acetylene and ethylene. PMID- 26822103 TI - A Synthetic Polymer Scaffold Reveals the Self-Maintenance Strategies of Rat Glioma Stem Cells by Organization of the Advantageous Niche. AB - Cancer stem cells (CSCs) are believed to be maintained within a microenvironmental niche. Here we used polymer microarrays for the rapid and efficient identification of glioma CSC (GSC) niche mimicries and identified a urethane-based synthetic polymer, upon which two groups of niche components, namely extracellular matrices (ECMs) and iron are revealed. In cultures, side population (SP) cells, defined as GSCs in the rat C6 glioma cell line, are more efficiently sustained in the presence of their differentiated progenies expressing higher levels of ECMs and transferrin, while in xenografts, ECMs are supplied by the vascular endothelial cells (VECs), including SP cell-derived ones with distinctively greater ability to retain xenobiotics than host VECs. Iron is stored in tumor infiltrating host macrophages (Mphis), whose protumoral activity is potently enhanced by SP cell-secreted soluble factor(s). Finally, coexpression of ECM-, iron-, and Mphi-related genes is found to be predictive of glioma patients' outcome. Our polymer-based approach reveals the intrinsic capacities of GSCs, to adapt the environment to organize a self-advantageous microenvironment niche, for their maintenance and expansion, which redefines the current concept of anti-CSC niche therapy and has the potential to accelerate cancer therapy development. Stem Cells 2016;34:1151-1162. PMID- 26822106 TI - Introduction to the Special Issue on Multilevel Models. PMID- 26822107 TI - Using Multilevel Modeling in the Evaluation of Community-Based Treatment Programs. PMID- 26822105 TI - Laser fluorescence in monitoring the influence of targeted tooth brushing on remineralization of initial caries lesions on newly erupted molar teeth - RCT. AB - OBJECTIVE: This study aimed to monitor mineralization changes in initial caries lesions on newly erupted second molars using laser fluorescence (LF) scanning after a 1-month targeted tooth brushing intervention. METHODS: Altogether, 124 13 to 14-year-old school children were invited to participate. Of those who fulfilled the clinical criteria (at least one initial lesion with LF value >10 in second molars), 51 gave their written consent to participate. Laser fluorescence values were registered at baseline and after 1-month follow-up period. All participants were individually taught targeted tooth brushing of their second molars and randomly provided tooth paste with 0 or 1500 ppm fluoride. Brushing frequency was investigated at baseline and after the follow-up. Change in LF values was compared considering the tooth, content of fluoride in the paste and brushing frequency. RESULTS: In lesions with LF values <=30 at baseline, change in LF values demonstrated improvement. Improvement was detected especially in upper molars. In lesions with LF values >30 at baseline, improvement was least detected. Brushing frequency increased slightly during the intervention. CONCLUSIONS: Laser fluorescence is a simple method and useful in monitoring remineralization of incipient lesions even in weeks. Targeted tooth brushing seems to induce remineralization even in weeks. Laser fluorescence could be a valuable motivating tool in promoting patients' self-care. PMID- 26822108 TI - Multilevel Models and Unbiased Tests for Group Based Interventions: Examples from the Safer Choices Study. AB - For many large-scale behavioral interventions, random assignment to intervention condition occurs at the group level. Data analytic models that ignore potential non-independence of observations provide inefficient parameter estimates and often produce biased test statistics. For studies in which individuals are randomized by groups to treatment condition, multilevel models (MLMs) provide a flexible approach to statistically evaluating program effects. This article presents an explanation of the need for MLM's for such nested designs and uses data from the Safer Choices study to illustrate the application of MLMs for both continuous and dichotomous outcomes. When designing studies, researchers who are considering group-randomized interventions should also consider the features of the multilevel analytic models they might employ. PMID- 26822109 TI - Explanatory Models for Relating Growth Processes. AB - For many purposes, longitudinal data are a great advance over cross-sectional data. The opportunities for modelling are enhanced if data for several occasions are obtained for a response, y, and at least one time-varying explanatory variable, x. The article describes, with examples, three modelling approaches when both y and x change over time. The first - a conditional approach - relates x to y in a regression framework. Earlier versions of these models were known as two-wave, two-variable (2W2V) 'causal' models. In the second, unconditional approach, growth or change parameters for x and y are themselves related in a second stage analysis. The third approach is based on structural equations modelling. All three approaches can be implemented in a multilevel framework. The article describes how multilevel models can extend the way we think about the analysis of longitudinal data, and hence how more interesting hypotheses about social processes can be modelled. PMID- 26822110 TI - Testing Predictive Developmental Hypotheses. AB - Predictive developmental hypotheses play a crucial role in developmental theories. These hypotheses link early developmental behaviors or processes to later developmental outcomes. Empirical tests of predictive developmental hypotheses are generally based on standard regression models. It is argued that hierarchical linear models or longitudinal multilevel models offer a better alternative. A multivariate longitudinal model linking developmental data to a criterion is described and an application is given. The application, derived from attachment theory, pertains to the prediction of infant behavior in the Strange Situation. It is concluded that the proposed approach offers a valuable tool to the developmentalist, both from a theoretical and methodological point of view. PMID- 26822111 TI - Multilevel Modeling of Individual and Group Level Mediated Effects. AB - This article combines procedures for single-level mediational analysis with multilevel modeling techniques in order to appropriately test mediational effects in clustered data. A simulation study compared the performance of these multilevel mediational models with that of single-level mediational models in clustered data with individual- or group-level initial independent variables, individual- or group-level mediators, and individual level outcomes. The standard errors of mediated effects from the multilevel solution were generally accurate, while those from the single-level procedure were downwardly biased, often by 20% or more. The multilevel advantage was greatest in those situations involving group-level variables, larger group sizes, and higher intraclass correlations in mediator and outcome variables. Multilevel mediational modeling methods were also applied to data from a preventive intervention designed to reduce intentions to use steroids among players on high school football teams. This example illustrates differences between single-level and multilevel mediational modeling in real-world clustered data and shows how the multilevel technique may lead to more accurate results. PMID- 26822112 TI - Multilevel Modeling of Cognitive Function in Schizophrenic Patients and Their First Degree Relatives. AB - We describe multilevel modeling of cognitive function in subjects with schizophrenia, their healthy first degree relatives and controls. The purpose of the study was to compare mean cognitive performance between the three groups after adjusting for various covariates, as well as to investigate differences in the variances. Multilevel models were required because subjects were nested within families and some of the measures were repeated several times on the same subject. The following four methodological issues that arose during the analysis of the data are discussed. First, when the random effects distribution was not normal, non-parametric maximum likelihood (NPML) was employed, leading to a different conclusion than the conventional multilevel model regarding one of the main study hypotheses. Second, the between-subject (within-family) variance was allowed to differ between the three groups. This corresponded to the variance at level 1 or level 2 depending on whether repeated measures were analyzed. Third, a positively skewed response was analyzed using a number of different generalized linear mixed models. Finally, penalized quasilikelihood (PQL) estimates for a binomial response were compared with estimates obtained using Gaussian quadrature. A small simulation study was carried out to assess the accuracy of the latter. PMID- 26822113 TI - FUS-mediated regulation of alternative RNA processing in neurons: insights from global transcriptome analysis. AB - Fused in sarcoma (FUS) is an RNA-binding protein that is causally associated with oncogenesis and neurodegeneration. Recently, the role of FUS in neurodegeneration has been extensively studied, because mutations in FUS are associated with amyotrophic lateral sclerosis (ALS), and the FUS protein has been identified as a major component of intracellular inclusions in neurodegenerative disorders including ALS and frontotemporal lobar degeneration. FUS is a key molecule in transcriptional regulation and RNA processing including processes such as pre messenger RNA (mRNA) splicing and polyadenylation. Interaction of FUS with various components of the transcription machinery, spliceosome, and the 3'-end processing machinery has been identified. Furthermore, recent advances in high throughput transcriptomic profiling approaches have enabled us to determine the mechanisms of FUS-dependent RNA processing networks at a cellular level. These analyses have revealed that depletion of FUS in neuronal cells affects alternative splicing and alternative polyadenylation of thousands of mRNAs. Gene ontology analysis has suggested that FUS-modulated genes are implicated in neuronal functions and development. CLIP-seq of FUS has shown that FUS is frequently clustered around these alternative sites of nascent RNA. ChIP-seq of RNA polymerase II (RNAP II) has demonstrated that an interaction between FUS and nascent RNA downregulates local transcriptional activity of RNAP II, which is critically involved in RNA processing. Both alternative splicing and alternative polyadenylation are fundamental processes by which cells expand their transcriptomic diversity, and are particularly essential in the nervous system. Dependence of transcriptomic diversity on FUS makes the nervous system vulnerable to neurodegeneration, when FUS is functionally compromised. WIREs RNA 2016, 7:330 340. doi: 10.1002/wrna.1338 For further resources related to this article, please visit the WIREs website. PMID- 26822114 TI - Serotonergic Modulation as Effective Treatment for Dravet Syndrome in a Zebrafish Mutant Model. AB - Dravet syndrome (DS) is a severe epilepsy syndrome that starts within the first year of life. In a clinical study, add-on treatment with fenfluramine, a potent 5 hydroxytryptamine (5-HT) releaser activating multiple 5-HT receptor subtypes, made 70% of DS children seizure free. Others and we recently confirmed the efficacy of fenfluramine as an antiepileptiform compound in zebrafish models of DS. By using a large set of subtype selective agonists, in this study we examined which 5-HT receptor subtypes can be targeted to trigger antiseizure effects in homozygous scn1Lab(-/-) mutant zebrafish larvae that recapitulate DS well. We also provide evidence that zebrafish larvae express the orthologues of all human 5-HT receptor subtypes. Using an automated larval locomotor behavior assay, we were able to show that selective 5-HT1D-, 5-HT1E-, 5-HT2A-, 5-HT2C-, and 5-HT7 agonists significantly decreased epileptiform activity in the mutant zebrafish at 7 days post fertilization (dpf). By measuring local field potentials in the zebrafish larval forebrain, we confirmed the antiepileptiform activity of the 5 HT1D-, 5-HT2C-, and especially the 5-HT2A-agonist. Interestingly, we also found a significant decrease of serotonin in the heads of homozygous scn1Lab(-/-) mutants as compared to the wild type zebrafish, which suggest that neurochemical defects might play a crucial role in the pathophysiology of DS. Taken together, our results emphasize the high conservation of the serotonergic receptors in zebrafish larvae. Modulating certain serotonergic receptors was shown to effectively reduce seizures. Our findings therefore open new avenues for the development of future novel DS therapeutics. PMID- 26822115 TI - Synthetic Receptors for the High-Affinity Recognition of O-GlcNAc Derivatives. AB - The combination of a pyrenyl tetraamine with an isophthaloyl spacer has led to two new water-soluble carbohydrate receptors ("synthetic lectins"). Both systems show outstanding affinities for derivatives of N-acetylglucosamine (GlcNAc) in aqueous solution. One receptor binds the methyl glycoside GlcNAc-beta-OMe with Ka ~20,000 m(-1), whereas the other one binds an O-GlcNAcylated peptide with Ka ~70,000 m(-1). These values substantially exceed those usually measured for GlcNAc-binding lectins. Slow exchange on the NMR timescale enabled structural determinations for several complexes. As expected, the carbohydrate units are sandwiched between the pyrenes, with the alkoxy and NHAc groups emerging at the sides. The high affinity of the GlcNAcyl-peptide complex can be explained by extra-cavity interactions, raising the possibility of a family of complementary receptors for O-GlcNAc in different contexts. PMID- 26822117 TI - Mobile genetic elements: in silico, in vitro, in vivo. AB - Mobile genetic elements (MGEs), also called transposable elements (TEs), represent universal components of most genomes and are intimately involved in nearly all aspects of genome organization, function and evolution. However, there is currently a gap between the fast pace of TE discovery in silico, driven by the exponential growth of comparative genomic studies, and a limited number of experimental models amenable to more traditional in vitro and in vivo studies of structural, mechanistic and regulatory properties of diverse MGEs. Experimental and computational scientists came together to bridge this gap at a recent conference, 'Mobile Genetic Elements: in silico, in vitro, in vivo', held at the Marine Biological Laboratory (MBL) in Woods Hole, MA, USA. PMID- 26822118 TI - Synergistic growth inhibitory effect of deracoxib with doxorubicin against a canine mammary tumor cell line, CMT-U27. AB - Cyclooxygenase (COX) inhibitors have been shown to exert anti-angiogenic and anti tumor activities on many types of malignant tumors. These anticancer properties make it worthwhile to examine the possible benefit of combining COX inhibitors with other anti-cancer agents. In the present study, we evaluated the potential of deracoxib (DER) in potentiating antitumor activity of doxorubicin (DOX) in canine mammary carcinoma cells (CMT-U27). DER (50-250 uM) enhanced the antiproliferative activity of DOX by reducing the IC50 (approximately 3- to 3.5 fold). Interaction analysis of the data showed that combinations of DOX at 0.9 uM with DER (100-250 uM) produced synergism in the CMT-U27 cell line, with a ratio index ranging from 1.98 to 2.33. In additional studies identifying the mechanism of observed synergistic effect, we found that DER strongly potentiated DOX-caused G0/G1 arrest in cell cycle progression. Also, DER (100-250 uM) augmented apoptosis induction with approximately 1.35- and 1.37- fold increases in apoptotic response caused by DOX in the cells. DER enhanced the antiproliferative effect of DOX in conjunction with induction of apoptosis by modulation of Bcl-2 expression and changes in the cell cycle of the CMT-U27 cell line. Although the exact molecular mechanism of the alterations in the cell cycle and apoptosis observed with DER and DOX combinations require further investigations, the results suggest that the synergistic effect of DOX and DER combinations in CMT therapy may be achieved at relatively lower doses of DOX with lesser side effects. Therefore, combining DER with DOX may prove beneficial in the clinical treatment of canine mammary cancer. PMID- 26822119 TI - Detection of infectious bronchitis virus strains similar to Japan in Taiwan. AB - A total of 1,320 tracheal samples from 66 broiler flocks sent to slaughterhouses and 42 tracheal samples from 42 flocks of local chickens in the field were collected for infectious bronchitis virus (IBV) gene detection by reverse transcription polymerase chain reaction using nucleocapsid-specific primers and spike-specific primers. Prevalence in broiler flocks was 39.4% (26/66) and in local chicken flocks was 11.9% (5/42). Several IBVs similar to Japan were detected in Taiwan. One-direction neutralization revealed that the reference antisera did not offer protection against the IBVs similar to those from Japan. PMID- 26822120 TI - Iridociliary adenocarcinoma with oncocytic change in a dog. AB - An intraocular mass lesion was found in the left eyeball in a spayed female Pembroke Welsh Corgi dog. The surgically resected left eyeball was pathologically examined. Histologically, the mass lesion consisted of proliferation of the atypical cuboidal or columnar epithelial cells, arranging in papillary, tubular or solid form. In addition, some neoplastic cells showed oncocytic change characterized as large oval cells with numerous eosinophilic intracytoplasmic granules. Cytoplasm of the oncocytic cells showed dark blue granules by phosphotungstic acid-hematoxylin stain. Immunohistochemically, the oncocytic cells were intensely positive for cytochrome C. Based on these findings, the ocular mass was diagnosed as iridociliary adenocarcinoma with oncocytic change. The findings indicate that the oncocytic changes of the neoplastic epithelial cells might be caused by mitochondrial accumulation. PMID- 26822122 TI - Berliner Wissenschaftspreis: P. Hegemann / Clara Immerwahr Award: R. L. Melen / Chemistry for the Future Solvay Prize: B. L. Feringa / Giulio Natta Medal and Lecture Award: K. Kohse-Hoinghaus. PMID- 26822121 TI - Reduced graphene oxide nanoshells for flexible and stretchable conductors. AB - Graphene has been extensively investigated for its use in flexible electronics, especially graphene synthesized by chemical vapor deposition (CVD). To enhance the flexibility of CVD graphene, wrinkles are often introduced. However, reports on the flexibility of reduced graphene oxide (RGO) films are few, because of their weak conductivity and, in particular, poor flexibility. To improve the flexibility of RGO, reduced graphene oxide nanoshells are fabricated, which combine self-assembled polystyrene nanosphere arrays and high-temperature thermal annealing processes. The resulting RGO films with nanoshells present a better resistance stabilization after stretching and bending the devices than RGO without nanoshells. The sustainability and performance advances demonstrated here are promising for the adoption of flexible electronics in a wide variety of future applications. PMID- 26822123 TI - Cerebrospinal fluid markers of neuronal and glial cell damage to monitor disease activity and predict long-term outcome in patients with autoimmune encephalitis. AB - BACKGROUND AND PURPOSE: Clinical symptoms and long-term outcome of autoimmune encephalitis are variable. Diagnosis requires multiple investigations, and treatment strategies must be individually tailored. Better biomarkers are needed for diagnosis, to monitor disease activity and to predict long-term outcome. The value of cerebrospinal fluid (CSF) markers of neuronal [neurofilament light chain protein (NFL), and total tau protein (T-tau)] and glial cell [glial fibrillary acidic protein (GFAP)] damage in patients with autoimmune encephalitis was investigated. METHODS: Demographic, clinical, magnetic resonance imaging, CSF and antibody-related data of 25 patients hospitalized for autoimmune encephalitis and followed for 1 year were retrospectively collected. Correlations between these data and consecutive CSF levels of NFL, T-tau and GFAP were investigated. Disability, assessed by the modified Rankin scale, was used for evaluation of disease activity and long-term outcome. RESULTS: The acute stage of autoimmune encephalitis was accompanied by high CSF levels of NFL and T-tau, whereas normal or significantly lower levels were observed after clinical improvement 1 year later. NFL and T-tau reacted in a similar way but at different speeds, with T-tau reacting faster. CSF levels of GFAP were initially moderately increased but did not change significantly later on. Final outcome (disability at 1 year) directly correlated with CSF-NFL and CSF-GFAP levels at all time-points and with CSF-T-tau at 3 +/- 1 months. This correlation remained significant after age adjustment for CSF-NFL and T-tau but not for GFAP. CONCLUSION: In autoimmune encephalitis, CSF levels of neuronal and glial cell damage markers appear to reflect disease activity and long-term disability. PMID- 26822125 TI - Visible-Light-Promoted Photocatalytic B-C Coupling via a Boron-Centered Carboranyl Radical: Facile Synthesis of B(3)-Arylated o-Carboranes. AB - A visible-light-mediated in situ generation of a boron-centered carboranyl radical (o-C2 B10 H11(.)) has been described. With eosin Y as a photoredox catalyst, 3-diazonium-o-carborane tetrafluoroborate [3-N2-o-C2B10H11][BF4] was converted into the corresponding boron-centered carboranyl radical intermediate, which can undergo efficient electrophilic substitution reaction with a wide range of (hetero)arenes. This general and simple procedure provides a metal-free alternative for the synthesis of 3-(hetero)arylated-o-carboranes. PMID- 26822124 TI - Heterogeneous dynamics, robustness/fragility trade-offs, and the eradication of the macroparasitic disease, lymphatic filariasis. AB - BACKGROUND: The current WHO-led initiative to eradicate the macroparasitic disease, lymphatic filariasis (LF), based on single-dose annual mass drug administration (MDA) represents one of the largest health programs devised to reduce the burden of tropical diseases. However, despite the advances made in instituting large-scale MDA programs in affected countries, a challenge to meeting the goal of global eradication is the heterogeneous transmission of LF across endemic regions, and the impact that such complexity may have on the effort required to interrupt transmission in all socioecological settings. METHODS: Here, we apply a Bayesian computer simulation procedure to fit transmission models of LF to field data assembled from 18 sites across the major LF endemic regions of Africa, Asia and Papua New Guinea, reflecting different ecological and vector characteristics, to investigate the impacts and implications of transmission heterogeneity and complexity on filarial infection dynamics, system robustness and control. RESULTS: We find firstly that LF elimination thresholds varied significantly between the 18 study communities owing to site variations in transmission and initial ecological parameters. We highlight how this variation in thresholds lead to the need for applying variable durations of interventions across endemic communities for achieving LF elimination; however, a major new result is the finding that filarial population responses to interventions ultimately reflect outcomes of interplays between dynamics and the biological architectures and processes that generate robustness/fragility trade-offs in parasite transmission. Intervention simulations carried out in this study further show how understanding these factors is also key to the design of options that would effectively eliminate LF from all settings. In this regard, we find how including vector control into MDA programs may not only offer a countermeasure that will reliably increase system fragility globally across all settings and hence provide a control option robust to differential locality-specific transmission dynamics, but by simultaneously reducing transmission regime variability also permit more reliable macroscopic predictions of intervention effects. CONCLUSIONS: Our results imply that a new approach, combining adaptive modelling of parasite transmission with the use of biological robustness as a design principle, is required if we are to both enhance understanding of complex parasitic infections and delineate options to facilitate their elimination effectively. PMID- 26822126 TI - Metabolic and Hormonal Response to a Feed-challenge Test in Lean and Overweight Dogs. AB - BACKGROUND: Obese dogs risk poor life quality, creating a need for increased knowledge of metabolism in overweight dogs. OBJECTIVES: Investigate postprandial metabolic and hormonal responses to a high-fat mixed-meal in dogs and responses of lean versus overweight dogs. ANIMALS: Twenty-eight healthy intact male Labrador Retrievers were included. METHODS: Prospective observational study. Twelve dogs were grouped as lean (body condition score (BCS 4-5), 10 as slightly overweight (BCS 6), and 6 as overweight (BCS 6.5-8) on a 9-point scale. After an overnight fast, urine and blood samples were collected. Dogs were then fed a high fat mixed-meal, and blood was collected hourly for 4 hours and urine after 3 hours. RESULTS: Postprandial concentrations of insulin and glucagon were increased at 1 hour (both P < 0.0001), triglycerides at 2 hours (P < 0.0001), and glucose at 3 hours (P = 0.004); and all remained increased throughout the feed challenge in all dogs. Postprandial urine cortisol/creatinine ratio was higher than fasting values (P = 0.001). Comparing between groups, there was an overall higher triglyceride response in overweight compared to lean (P = 0.001) and slightly overweight (P = 0.015) dogs. Overweight dogs also had higher fasting cortisol/creatinine ratio compared to lean dogs (P = 0.024). CONCLUSIONS AND CLINICAL IMPORTANCE: Postprandial responses of dogs to a high-fat mixed-meal were similar to those previously reported in people. The higher postprandial triglyceride response and fasting cortisol/creatinine ratio in the overweight dogs could be early signs of metabolic imbalance. Thus, although overweight dogs often appear healthy, metabolic alterations might be present. PMID- 26822127 TI - Granulocyte colony-stimulating factor promotes behavioral recovery in a mouse model of traumatic brain injury. AB - Hematopoietic growth factors such as granulocyte colony-stimulating factor (G CSF) represent a novel approach for treatment of traumatic brain injury (TBI). After mild controlled cortical impact (CCI), mice were treated with G-CSF (100 MUg/kg) for 3 consecutive days. The primary behavioral endpoint was performance on the radial arm water maze (RAWM), assessed 7 and 14 days after CCI. Secondary endpoints included 1) motor performance on a rotating cylinder (rotarod), 2) measurement of microglial and astroglial response, 3) hippocampal neurogenesis, and 4) measures of neurotrophic factors (brain-derived neurotrophic factor [BDNF] and glial cell line-derived neurotrophic factor [GDNF]) and cytokines in brain homogenates. G-CSF-treated animals performed significantly better than vehicle treated mice in the RAWM at 1 and 2 weeks but not on the rotarod. Cellular changes found in the G-CSF group included increased hippocampal neurogenesis as well as astrocytosis and microgliosis in both the striatum and the hippocampus. Neurotrophic factors GDNF and BDNF, elaborated by activated microglia and astrocytes, were increased in G-CSF-treated mice. These factors along with G-CSF itself are known to promote hippocampal neurogenesis and inhibit apoptosis and likely contributed to improvement in the hippocampal-dependent learning task. Six cytokines that were modulated by G-CSF treatment following CCI were elevated on day 3, but only one of them remained altered by day 7, and all of them were no different from vehicle controls by day 14. The pro- and anti-inflammatory cytokines modulated by G-CSF administration interact in a complex and incompletely understood network involving both damage and recovery processes, underscoring the dual role of inflammation after TBI. PMID- 26822128 TI - Segmental basal cell naevus syndrome caused by an activating mutation in smoothened. AB - Aberrant sonic hedgehog signalling, mostly due to PTCH1 mutations, has been shown to play a central role in the pathogenesis of basal cell carcinoma (BCC), as well as in basal cell naevus syndrome (BCNS). Mutations in smoothened (SMO) encoding a receptor for sonic hedgehog have been reported in sporadic BCCs but not in BCNS. We report a case with multiple BCCs, pits and comedones in a segmental distribution over the upper part of the body, along with other findings compatible with BCNS. Histopathologically, there were different types of BCC. A heterozygous mutation (c.1234C>T, p.L412F) in SMO was detected in three BCCs but not in peripheral blood lymphocytes or the uninvolved skin. These were compatible with the type 1 mosaic form of BCNS. The p.L412F mutation was found experimentally to result in increased SMO transactivating activity, and the patient responded to vismodegib therapy. Activating mutations in SMO may cause BCNS. The identification of a gain-of-function mutation in SMO causing a type 1 mosaic form of BCNS further expands our understanding of the pathogenesis of BCC, with implications for the treatment of these tumours, whether sporadic or inherited. PMID- 26822130 TI - The neonatal tetrahydrobiopterin loading test in phenylketonuria: what is the predictive value? AB - BACKGROUND: It is unknown whether the neonatal tetrahydrobiopterin (BH4) loading test is adequate to diagnose long-term BH4 responsiveness in PKU. Therefore we compared the predictive value of the neonatal (test I) versus the 48-h BH4 loading test (test II) and long-term BH4 responsiveness. METHODS: Data on test I (>1991, 20 mg/kg) at T = 8 (n = 85) and T = 24 (n = 5) were collected and compared with test II and long-term BH4 responsiveness at later age, with >=30% Phe decrease used as the cut-off. RESULTS: The median (IQR) age at hospital diagnosis was 9 (7-11) days and the age at test II was 11.8 (6.6-13.7) years. The baseline Phe concentrations at test I were significantly higher compared to test II (1309 (834-1710) versus 514 (402-689) MUmol/L, respectively, P = 0.000). 15/85 patients had a positive test I T = 8. All, except one patient who was not tested for long-term BH4 responsiveness, showed long-term BH4 responsiveness. In 20/70 patients with a negative test I T = 8, long-term BH4 responsiveness was confirmed. Of 5 patients with a test I T = 24, 1/5 was positive at both tests and showed long-term BH4 responsiveness, 2/5 had negative results at both tests and 2/5 showed a negative test I T = 24, but a positive test II with 1/2 showing long term BH4 responsiveness. CONCLUSIONS: Both a positive neonatal 8- and 24-h BH4 loading test are predictive for long-term BH4 responsiveness. However, a negative test does not rule out long-term BH4 responsiveness. Other alternatives to test for BH4 responsiveness at neonatal age should be investigated. PMID- 26822131 TI - Creating District Readiness for Implementing Evidence-Based School-Centered Asthma Programs: Denver Public Schools as a Case Study. AB - Asthma is a common chronic childhood disease that is associated with high rates of school absenteeism and educational disparities. Effective school-based programs exist that are able to reduce school absenteeism and the burden that asthma exacts on students. However, despite the availability of effective school centered asthma programs conducted as research projects, many schools have struggled to implement the programs and experience their benefits. As the literature from the implementation sciences highlights, readiness of the school environment is crucial and central to success. This is an often overlooked and underacknowledged aspect to successful implementation. This article provides a case study of a large school district, highlighting its experience in preparing the district for broad-scale implementation of a school-centered asthma program. PMID- 26822129 TI - Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity. AB - Obesity-induced kidney injury contributes to albuminuria, which is characterized by a progressive decline in renal function leading to glomerulosclerosis and renal fibrosis. Matrix metalloproteinases (MMPs) modulate inflammation and fibrosis by degrading a variety of extracellular matrix and regulating the activities of effector proteins. Abnormal regulation of MMP-12 expression has been implicated in abdominal aortic aneurysm, atherosclerosis, and emphysema, but the underlying mechanisms remain unclear. The present study examined the function of MMP-12 in glomerular fibrogenesis and inflammation using apo E(-/-) or apo E( /-)MMP-12(-/-) mice and maintained on a high-fat-diet (HFD) for 3, 6, or 9 months. MMP-12 deletion reduced glomerular matrix accumulation, and downregulated the expression of NADPH oxidase 4 and the subunit-p67(phox), indicating the inhibition of renal oxidative stress. In addition, the expression of the inflammation-associated molecule MCP-1 and macrophage marker-CD11b was decreased in glomeruli of apo E(-/-)MMP-12(-/-) mice fed HFD. MMP-12 produced by macrophages infiltrating into glomeruli contributed to the degradation of collagen type IV and fibronectin. Crescent formation due to renal oxidative stress in Bowman's space was a major factor in the development of fibrogenesis and inflammation. These results suggest that regulating MMP-12 activity could be a therapeutic strategy for the treatment of crescentic glomerulonephritis and fibrogenesis. PMID- 26822132 TI - Implementing 12345 Fit-Tastic: A Tool for Combating Childhood Obesity. AB - Childhood obesity is epidemic in the United States. School nurses are in a unique position to address weight with the students they serve. This article provides tools for school nurses to be able to conduct an obesity screening, demonstrate the basic skills of motivational interviewing in treatment of obesity in a school age child, and utilize the 12345 Fit-Tastic program in their practice. This article is the seventh and final article in a series on the topic of childhood obesity and the accompanying comorbidities. PMID- 26822133 TI - Too Busy for TB: Managing a Case of Tuberculosis Disease in the School Setting. AB - School nurses actively monitor the school population for signs of communicable disease on a daily basis. State regulations outline reportable diseases and provide guidance to control disease outbreak, including management of disease outbreak in the school setting. The purpose of this article is to review strategies recently used in managing a tuberculosis (TB) outbreak at a large high school in Kansas. A timeline of events is presented along with a discussion of the differences between latent TB infection and TB disease. Partnering across agencies and departments enabled the timely testing of over 400 individuals and subsequent management of individuals testing positive for latent TB infection. Public information officers provided necessary guidance to communicate to audiences both internally and externally. PMID- 26822134 TI - The Postcard Initiative: Personal Communication From Students Can Increase Timely Compliance With Health Requirements. AB - BACKGROUND: Immunizations and physical exams ensure the health and safety of school children. Failure to comply with state regulations can lead to exclusion from school activities. METHODS: Students in fifth and eighth grades personalized postcards that contained health requirements for entry into sixth (junior high) and ninth (high school). The postcards were mailed three times over the school year. The junior high had a decline in first-day exclusions that did not reach significance. The high school decreased first-day exclusions from 6.4% to 1.6%. Both schools had significantly more physicals turned in before August 1 when compared with the previous year. CONCLUSION: Communicating health requirements by personalized postcards provides information in a manner that is better understood by parents/guardians. PMID- 26822135 TI - Testing a Dual Process Model of Gender-Based Violence: A Laboratory Examination. AB - The dire impact of gender-based violence on society compels development of models comprehensive enough to capture the diversity of its forms. Research has established hostile sexism (HS) as a robust predictor of gender-based violence. However, to date, research has yet to link men's benevolent sexism (BS) to physical aggression toward women, despite correlations between BS and HS and between BS and victim blaming. One model, the opposing process model of benevolent sexism (Sibley & Perry, 2010), suggests that, for men, BS acts indirectly through HS to predict acceptance of hierarchy-enhancing social policy as an expression of a preference for in-group dominance (i. e., social dominance orientation [SDO]). The extent to which this model applies to gender-based violence remains untested. Therefore, in this study, 168 undergraduate men in a U. S. university participated in a competitive reaction time task, during which they had the option to shock an ostensible female opponent as a measure of gender based violence. Results of multiple-mediation path analyses indicated dual pathways potentiating gender-based violence and highlight SDO as a particularly potent mechanism of this violence. Findings are discussed in terms of group dynamics and norm-based violence prevention. PMID- 26822136 TI - A trehalase from Zunongwangia sp.: characterization and improving catalytic efficiency by directed evolution. AB - BACKGROUND: Trehalases have potential applications in several fields, including food additives, insecticide development, and transgenic plant. In the present study, we focused on a trehalase from the marine bacterium Zunongwangia sp., which hydrolyzes trehalose to glucose. RESULTS: A novel gene, treZ (1590 bp) encoding an alpha, alpha-trehalase of 529 amino acids was cloned from Zunongwangia sp., and TreZ was found to have an optimal activity at 50 degrees C and pH 6. The activity of TreZ was increased by the presence of NaCl, showing the highest activity (136 %) at 1 M NaCl. A variant C4 with improved catalytic activity was obtained by error-prone PCR and followed by a 96-well plate high throughput screening. The variant C4 with two altered sites (Y227H, and R442G) displayed a 3.3 fold increase in catalytic efficiency (k cat/K m, 1143.40 mmol( 1) s(-1)) compared with the wild type enzyme (265.91 mmol(-1) s(-1)). In order to explore the contribution of the mutations found in variant C4 to the increased catalytic activity, two mutants Y227H and R442G were constructed by site-directed mutagenesis. The results showed that the catalytic efficiencies of Y227H and R442G were 416.78 mmol(-1) s(-1) and 740.97 mmol(-1) s(-1), respectively, indicating that both mutations contributed to the increased catalytic efficiency of variant C4. The structure modeling and substrate docking revealed that the substitution Y227H enlarged the shape of the binding pocket, to improve the binding of the substrate and the release of the products; while the substitution R442G reduced the size of the side chain and decreased the steric hindrance, which contributed to channel the substrate into the active cavity easier and promote the release of the product. CONCLUSION: In this study, a novel trehalase was cloned, purified, characterized, and engineered. A variant C4 with dramatically improved catalytic activity was obtained by directed evolution, and the mutation sites Y227H and R442G were found to play a significant role in the catalytic efficiency. The overall results provide useful information about the structure and function of trehalase. PMID- 26822137 TI - Ultrasonography-guided penile block for adult penile surgery. PMID- 26822138 TI - Isolation, complete genome sequencing, and phylogenetic analysis of the first Chuzan virus in China. AB - A Chuzan virus (CHUV), defined as GX871 here, was isolated from blood from a sentinel cattle firstly in China, and its full-length genome was sequenced in this study. The GX871 genome included 10 segments and 18914 bp, one base fewer than the CHUV prototype strain K-47 due to a one-base deletion in the 5' non coding region of segment 8. A frameshift mutation was detected in a short coding region (1010-1026 nt) corresponding to the VP1 protein; this frameshift resulted in a five-amino acid mutation from 336CVLSY340 to 336YGAKL340. In addition, there were a one-base deletion at 1713 nt and a one-base insertion at 1682 nt in the 3' non-coding region of segment 5. Based on phylogenetic analysis of the deduced VP2 amino acid sequences, Palyam serogroup viruses were classified into three groups. The Chinese CHUV isolate GX871 was categorized into the same group as CHUV prototype strain K-47. The phylogenetic tree was divided into three clusters according to the geographical distribution of the partial nucleotide sequences of VP7, and this arrangement might define the geographical gene pool of CHUV. PMID- 26822139 TI - Abyssivirga alkaniphila gen. nov., sp. nov., an alkane-degrading, anaerobic bacterium from a deep-sea hydrothermal vent system, and emended descriptions of Natranaerovirga pectinivora and Natranaerovirga hydrolytica. AB - A strictly anaerobic, mesophilic, syntrophic, alkane-degrading strain, L81T, was isolated from a biofilm sampled from a black smoker chimney at the Loki's Castle vent field. Cells were straight, rod-shaped, Gram-positive-staining and motile. Growth was observed at pH 6.2-9.5, 14-42 degrees C and 0.5-6 % (w/w) NaCl, with optima at pH 7.0-8.2, 37 degrees C and 3% (w/w) NaCl. Proteinaceous substrates, sugars, organic acids and hydrocarbons were utilized for growth. Thiosulfate was used as an external electron acceptor during growth on crude oil. Strain L81T was capable of syntrophic hydrocarbon degradation when co-cultured with a methanogenic archaeon, designated strain LG6, isolated from the same enrichment. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain L81T is affiliated with the family Lachnospiraceae, and is most closely related to the type strains of Natranaerovirga pectinivora (92 % sequence similarity) and Natranaerovirga hydrolytica (90%). The major cellular fatty acids of strain L81T were C15 : 0, anteiso-C15 : 0 and C16 : 0, and the profile was distinct from those of the species of the genus Natranaerovirga. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol, three unidentified phospholipids, four unidentified glycolipids and two unidentified phosphoglycolipids. The G+C content of genomic DNA was determined to be 31.7 mol%. Based on our phenotypic, phylogenetic and chemotaxonomic results, strain L81T is considered to represent a novel species of a new genus of the family Lachnospiraceae, for which we propose the name Abyssivirga alkaniphila gen. nov., sp. nov. The type strain of Abyssivirga alkaniphila is L81T (=DSM 29592T=JCM 30920T). We also provide emended descriptions of Natranaerovirga pectinivora and Natranaerovirga hydrolytica. PMID- 26822140 TI - Diaphragm degeneration and cardiac structure in mdx mouse: potential clinical implications for Duchenne muscular dystrophy. AB - We examined the effects of exercise on diaphragm degeneration and cardiomyopathy in dystrophin-deficient mdx mice. Mdx mice (11 months of age) were exercised (swimming) for 2 months to worsen diaphragm degeneration. Control mdx mice were kept sedentary. Morphological evaluation demonstrated increased fibrosis in the diaphragm of exercised mdx mice (33.3 +/- 6.0% area of fibrosis) compared with control mdx mice (20.9 +/- 1.7% area of fibrosis). Increased (26%) activity of MMP-2, a marker of fibrosis, was detected in the diaphragms from exercised mdx mice. Morphological evaluation of the heart demonstrated a 45% increase in fibrosis in the right ventricle (8.3 +/- 0.6% in sedentary vs. 12.0 +/- 0.6% of fibrosis in exercised) and in the left ventricle (35% increase) in the exercised mdx mice. The density of inflammatory cells-degenerating cardiomyocytes increased 95% in the right ventricle (2.3 +/- 0.6 in sedentary vs. 4.5 +/- 0.8 in exercised) and 71% in the left ventricle (1.4 +/- 0.6 sedentary vs. 2.4 +/- 0.5 exercised). The levels of both active MMP-2 and the pro-fibrotic factor transforming growth factor beta were elevated in the hearts of exercised compared with sedentary mdx mice. The wall thickness to lumen diameter ratio of the pulmonary trunk was significantly increased in the exercised mdx mice (0.11 +/- 0.04 in sedentary vs. 0.28 +/- 0.12 in exercised), as was the thickness of the right ventricle wall, which suggests the occurrence of pulmonary hypertension in those animals. It is suggested that diaphragm degeneration is a main contributor to right ventricle dystrophic pathology. These findings may be relevant for future interventional studies for Duchenne muscular dystrophy-associated cardiomyopathy. PMID- 26822141 TI - Towards a novel bioelectrocatalytic platform based on "wiring" of pyrroloquinoline quinone-dependent glucose dehydrogenase with an electrospun conductive polymeric fiber architecture. AB - Electrospinning is known as a fabrication technique for electrode architectures that serve as immobilization matrices for biomolecules. The current work demonstrates a novel approach to construct a conductive polymeric platform, capable not only of immobilization, but also of electrical connection of the biomolecule with the electrode. It is produced upon electrospinning from mixtures of three different highly conductive sulfonated polyanilines and polyacrylonitrile on ITO electrodes. The resulting fiber mats are with a well retained conductivity. After coupling the enzyme pyrroloquinoline quinone dependent glucose dehydrogenase (PQQ-GDH) to polymeric structures and addition of the substrate glucose an efficient bioelectrocatalysis is demonstrated. Depending on the choice of the sulfonated polyanilline mediatorless bioelectrocatalysis starts at low potentials; no large overpotential is needed to drive the reaction. Thus, the electrospun conductive immobilization matrix acts here as a transducing element, representing a promising strategy to use 3D polymeric scaffolds as wiring agents for active enzymes. In addition, the mild and well reproducible fabrication process and the active role of the polymer film in withdrawing electrons from the reduced PQQ-GDH lead to a system with high stability. This could provide access to a larger group of enzymes for bioelectrochemical applications including biosensors and biofuel cells. PMID- 26822142 TI - Implementation of a high-performance cardiopulmonary resuscitation protocol at a collegiate emergency medical services program. AB - Out-of-hospital cardiac arrest (OHCA) is a significant public health issue. Although OHCA occurs relatively infrequently in the collegiate environment, educational institutions with on-campus emergency medical services (EMS) agencies are uniquely positioned to provide high-quality resuscitation care in an expedient fashion. Georgetown University's on-campus EMS program recently updated its medical protocols to reflect the latest literature in resuscitation science. In a high-performance CPR (HPCPR) resuscitation, minimally interrupted chest compressions are emphasized, along with a coordinated team-based approach. PMID- 26822143 TI - Synthesis and SAR assessment of novel Tubathian analogs in the pursuit of potent and selective HDAC6 inhibitors. AB - The synthesis of novel isoform-selective HDAC inhibitors is considered to be an important, emerging field in medicinal chemistry. In this paper, the preparation and assessment of thirteen selective HDAC6 inhibitors is disclosed, elaborating on a previously developed thiaheterocyclic Tubathian series. All compounds were evaluated in vitro for their ability to inhibit HDAC6, and a selection of five potent compounds was further screened toward all HDAC isoforms (HDAC1-11). The capability of these Tubathian analogs to inhibit alpha-tubulin deacetylation was assessed as well, and ADME/Tox data were collected. This thorough SAR evaluation revealed that the oxidized, para-substituted hydroxamic acids can be recognized as valuable lead structures in the pursuit of novel potent and selective HDAC6 inhibitors. PMID- 26822144 TI - Broadening the implications of gene discovery. PMID- 26822146 TI - Double-blind, placebo-controlled, proof-of-concept trial of bexarotene Xin moderate Alzheimer's disease. AB - BACKGROUND: We assessed the impact of retinoid X receptor (RXR) agonist bexarotene on brain amyloid measured by amyloid imaging in patients with Alzheimer's disease (AD) in a proof-of-concept trial. METHODS: Twenty patients with AD [Mini Mental State Examination (MMSE) score 10-20 inclusive] with positive florbetapir scans were randomized to receive 300 mg of bexarotene or placebo for 4 weeks. The amyloid imaging result was the primary outcome. Whole population analyses and prespecified analyses by genotype [apolipoprotein E epsilon4 (ApoE4) carriers and ApoE4 noncarriers] were conducted. Secondary outcomes included scores on the Alzheimer's Disease Assessment Scale-Cognitive subscale, Alzheimer's Disease Cooperative Study-Activities of Daily Living scale, MMSE, Clinical Dementia Rating scale, and Neuropsychiatric Inventory. Serum amyloid-beta (Abeta) peptide sequences Abeta1-40 and Abeta1-42 measurements were collected as biomarker outcomes. RESULTS: There was no change in the composite or regional amyloid burden when all patients were included in the analysis. ApoE4 noncarriers showed a significant reduction in brain amyloid on the composite measure in five of six regional measurements. No change in amyloid burden was observed in ApoE4 carriers. There was a significant association between increased serum Abeta1-42 and reductions in brain amyloid in ApoE4 noncarriers (not in carriers). There were significant elevations in serum triglycerides in bexarotene treated patients. There was no consistent change in any clinical measure. CONCLUSIONS: The primary outcome of this trial was negative. The data suggest that bexarotene reduced brain amyloid and increased serum Abeta1-42 in ApoE4 noncarriers. Elevated triglycerides could represent a cardiovascular risk, and bexarotene should not be administered outside a research setting. RXR agonists warrant further investigations as AD therapies. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01782742 . Registered 29 January 2013. PMID- 26822147 TI - A potential anatomic subtype of short bowel syndrome: a matched case-control study. AB - BACKGROUND: Fundamental researches suggest that ileum presents greater adaptive potential than the jejunum. However, few studies estimate the association between ileum and adaptive potential in human. To discover the association, we conducted this matched case-control study. METHODS: A 1:2 pair-matched, case-control study was conducted from January 1, 2001 to January 1, 2015 in Intestinal Rehabilition and Transplant Center. The case group was ileum predominated (IP) group and the control group was jejunum predominated (JP) group. Demographic data, medical history and progression of each patient were collected. RESULTS: There were 24 IP cases and 48 JP controls in this study. The cumulative probabilities of parenteral nutrition (PN) weaning in IP group were higher than that in JP group. The Bristol stool scale scores of IP group were lower than that of JP group at third month. The Cox proportional hazards regression model confirmed that IP had a higher odds of PN weaning (OR = 2.69; 95 % CI: 1.27, 5.70, p = 0.01) as compared with JP group. The conditional logistic regression with 1:2 matching also confirmed IP group had a higher odds (OR = 4.84; 95 % CI: 2.02, 11.56, p <0.01). CONCLUSIONS: Our results indicated that ileum presents greater adaptive potential than the jejunum in nutrition and fluid absorption. And a potential anatomic subtype of short bowel syndrome was proposed. Further research need to be conducted to more fully understand the adaptive potential of ileum besides nutrition and fluid absorption. PMID- 26822148 TI - The impact of sequencing on diagnosis and treatment of malignant melanoma. AB - Melanoma is one of the clinically most important cancer types considering its high mortality rate and that it is commonly diagnosed in relatively young people. With the advent of targeted therapies and, more recently, immune checkpoint inhibitors, more treatment options are available resulting in higher patient survival rates. However, the successful application of these targeted therapies critically depends on the reliable detection of molecular aberrations. Today, massively parallel sequencing techniques enable us to analyze large sets of genes in a relatively short time. It has allowed increased knowledge of acquired somatic mutations in melanoma and has helped to identify new targets for personalized therapy, and potentially may help to predict response to immune therapies. Described here are the development of sequencing techniques, how their improvement has changed diagnosis, prognosis and management of malignant melanoma and the future perspectives of melanoma diagnostics in the routine clinical setting. PMID- 26822149 TI - Multicenter Feasibility Study of Tumor Molecular Profiling to Inform Therapeutic Decisions in Advanced Pediatric Solid Tumors: The Individualized Cancer Therapy (iCat) Study. AB - Importance: Pediatric cancers represent a unique case with respect to cancer genomics and precision medicine, as the mutation frequency is low, and targeted therapies are less available. Consequently, it is unknown whether clinical sequencing can be of benefit. Objective: To assess the feasibility of identifying actionable alterations and making individualized cancer therapy (iCat) recommendations in pediatric patients with extracranial solid tumors. Design, Setting, and Participants: Clinical sequencing study at 4 academic medical centers enrolling patients between September 5, 2012, and November 19, 2013, with 1 year of clinical follow-up. Participants were 30 years or younger with high risk, recurrent, or refractory extracranial solid tumors. The data analysis was performed October 28, 2014. Interventions: Tumor profiling performed on archived clinically acquired specimens consisted of mutation detection by a Sequenom assay or targeted next-generation sequencing and copy number assessment by array comparative genomic hybridization. Results were reviewed by a multidisciplinary expert panel, and iCat recommendations were made if an actionable alteration was present, and an appropriate drug was available. Main Outcomes and Measures: Feasibility was assessed using a 2-stage design based on the proportion of patients with recommendations. Results: Of 100 participants (60 male; median [range] age, 13.4 [0.8-29.8] years), profiling was technically successful in 89 (89% [95% CI, 83%-95%]). Median (range) follow-up was 6.8 (2.0-23.6) months. Overall, 31 (31% [95% CI, 23%-41%]) patients received an iCat recommendation and 3 received matched therapy. The most common actionable alterations leading to an iCat recommendation were cancer-associated signaling pathway gene mutations (n = 10) and copy number alterations in MYC/MYCN (n = 6) and cell cycle genes (n = 11). Additional alterations with implications for clinical care but not resulting in iCat recommendations were identified, including mutations indicating the possible presence of a cancer predisposition syndrome and translocations suggesting a change in diagnosis. In total, 43 (43% [95% CI, 33%-53%]) participants had results with potential clinical significance. Conclusions and Relevance: A multi-institution clinical genomics study in pediatric oncology is feasible and a substantial proportion of relapsed or refractory pediatric solid tumors have actionable alterations. Trial Registration: clinicaltrials.gov Identifier: NCT01853345. PMID- 26822150 TI - Human endometrial regenerative cells attenuate renal ischemia reperfusion injury in mice. AB - BACKGROUND: Endometrial regenerative cells (ERCs) is an attractive novel type of adult mesenchymal stem cells that can be non-invasively obtained from menstrual blood and are easily replicated at a large scale without tumorigenesis. We have previously reported that ERCs exhibit unique immunoregulatory properties in experimental studies in vitro and in vivo. In this study, the protective effects of ERCs on renal ischemia-reperfusion injury (IRI) were examined. METHODS: Renal IRI in C57BL/6 mice was induced by clipping bilateral renal pedicles for 30 min, followed by reperfusion for 48 h. ERCs were isolated from healthy female menstrual blood, and were injected (1 million/mouse, i.v.) into mice 2 h prior to IRI induction. Renal function, pathological and immunohistological changes, cell populations and cytokine profiles were evaluated after 48 h of renal reperfusion. RESULTS: Here, we showed that as compared to untreated controls, administration of ERCs effectively prevented renal damage after IRI, indicated by better renal function and less pathological changes, which were associated with increased serum levels of IL-4, but decreased levels of TNF-alpha, IFN-gamma and IL-6. Also, ERC-treated mice displayed significantly less splenic and renal CD4(+) and CD8(+) T cell populations, while the percentage of splenic CD4(+)CD25(+) regulatory T cells and infiltrating M2 macrophages in the kidneys were significantly increased in ERC-treated mice. CONCLUSIONS: This study demonstrates that the novel anti-inflammatory and immunoregulatory effects of ERCs are associated with attenuation of renal IRI, suggesting that the unique features of ERCs may make them a promising candidate for cell therapies in the treatment of ischemic acute kidney injury in patients. PMID- 26822152 TI - Can the self become another? Investigating the effects of self-association with a new facial identity. AB - The mental representation of the self is a complex construct, comprising both conceptual information and perceptual information regarding the body. Evidence suggests that both the conceptual self-representation and the bodily self representation are malleable, and that these different aspects of the self are linked. Changes in bodily self-representation appear to affect how the self is conceptualized, but it is unclear whether the opposite relationship is also true: Do changes to the conceptual self-representation affect how the physical self is perceived? First, we adopted a perceptual matching paradigm to establish an association between the self and an unfamiliar face (Experiment 1). Robust attentional and perceptual biases in the processing of this newly self-associated object suggested that the conceptual self-representation was extended to include it. Next, we measured whether the bodily self-representation had correspondingly changed to incorporate the new face (Experiment 2). Participants rated morphs between their own and the newly-associated according to how similar they were to the self, before and after performing the perceptual matching task. Changes to the conceptual self did not have an effect on the bodily self-representation. These results suggest that modulatory links between aspects of the mental self representation, when focused on the non-social self, are unidirectional and flow in a bottom-up manner. PMID- 26822151 TI - Genome-wide association study and targeted metabolomics identifies sex-specific association of CPS1 with coronary artery disease. AB - Metabolites derived from dietary choline and L-carnitine, such as trimethylamine N-oxide and betaine, have recently been identified as novel risk factors for atherosclerosis in mice and humans. We sought to identify genetic factors associated with plasma betaine levels and determine their effect on risk of coronary artery disease (CAD). A two-stage genome-wide association study (GWAS) identified two significantly associated loci on chromosomes 2q34 and 5q14.1. The lead variant on 2q24 (rs715) localizes to carbamoyl-phosphate synthase 1 (CPS1), which encodes a mitochondrial enzyme that catalyses the first committed reaction and rate-limiting step in the urea cycle. Rs715 is also significantly associated with decreased levels of urea cycle metabolites and increased plasma glycine levels. Notably, rs715 yield a strikingly significant and protective association with decreased risk of CAD in only women. These results suggest that glycine metabolism and/or the urea cycle represent potentially novel sex-specific mechanisms for the development of atherosclerosis. PMID- 26822153 TI - Small RNAs Recruit Chromatin-Modifying Enzymes MMSET and Tip60 to Reconfigure Damaged DNA upon Double-Strand Break and Facilitate Repair. AB - Recent reports have demonstrated that DNA double-strand break (DSB)-induced small RNAs (diRNA) play an important role in the DNA damage response (DDR). However, the molecular mechanism by which diRNAs regulate the DDR remains unclear. Here, we report that Dicer- and Drosha-dependent diRNAs function as guiding molecules to promote the recruitment of the methyltransferase MMSET (WHSC1) and the acetyltransferase Tip60 (KAT5) to the DSB, where local levels of histone H4 di- and tri-methylation at lysine 20 (H4K20me2, 3) and H4 acetylation at lysine 16 (H4K16Ac) were enhanced. These histone modification events resulted in an open, flexible chromatin configuration, as indicated by the increased release of histones gammaH2AX, H2AX, and H3 from damaged chromatin. Furthermore, we found that diRNA-associated AGO2 interacted with MMSET and Tip60 and that the diRNA binding and catalytic activities of AGO2 were dispensable for the interaction but required for the recruitment of MMSET and Tip60 to DSBs. Consequently, diRNA mediated chromatin remodeling promoted DSB repair by enhancing the recruitment of Rad51 and BRCA1 to the DSB site. Taken together, our findings reveal an unexpected direct role for diRNAs in regulating chromatin remodeling to facilitate DSB repair, revealing a new layer of DDR regulation involving specialized RNA molecules. Cancer Res; 76(7); 1904-15. (c)2016 AACR. PMID- 26822155 TI - The Surgical Workforce and Surgical Provider Productivity in Sierra Leone: A Countrywide Inventory. AB - BACKGROUND: Limited data exist on surgical providers and their scope of practice in low-income countries (LICs). The aim of this study was to assess the distribution and productivity of all surgical providers in an LIC, and to evaluate correlations between the surgical workforce availability, productivity, rates, and volume of surgery at the district and hospital levels. METHODS: Data on surgeries and surgical providers from 56 (93.3 %) out of 60 healthcare facilities providing surgery in Sierra Leone in 2012 were retrieved between January and May 2013 from operation theater logbooks and through interviews with key informants. RESULTS: The Sierra Leonean surgical workforce consisted of 164 full-time positions, equal to 2.7 surgical providers/100,000 inhabitants. Non specialists performed 52.8 % of all surgeries. In rural areas, the densities of specialists and physicians were 26.8 and 6.3 times lower, respectively, compared with urban areas. The average individual productivity was 2.8 surgeries per week, and varied considerably between the cadres of surgical providers and locations. When excluding four centers that only performed ophthalmic surgery, there was a positive correlation between a facility's volume of surgery and the productivity of its surgical providers (r s = 0.642, p < 0.001). CONCLUSIONS: Less than half of all of the surgery in Sierra Leone is performed by specialists. Surgical providers were significantly more productive in healthcare facilities with higher volumes of surgery. If all surgical providers were as productive as specialists in the private non-profit sector (5.1 procedures/week), the national volume of surgery would increase by 85 %. PMID- 26822154 TI - The Dual MEK/FLT3 Inhibitor E6201 Exerts Cytotoxic Activity against Acute Myeloid Leukemia Cells Harboring Resistance-Conferring FLT3 Mutations. AB - Fms-like tyrosine kinase 3 (FLT3) inhibition has elicited encouraging responses in acute myeloid leukemia (AML) therapy. Unfortunately, unless combined with a bone marrow transplant, disease relapse is frequent. In addition to the acquired point mutations in the FLT3 kinase domain that contribute to FLT3 inhibitor resistance, MEK/ERK signaling is persistently activated in AML cells even when FLT3 phosphorylation is continually suppressed. Thus, concomitant targeting of FLT3 and MAPK may potentially exert synergistic activity to counteract the resistance of AML cells to FLT3-targeted therapy. In this study, we investigated the antileukemia activity of a MEK1 and FLT3 dual inhibitor, E6201, in AML cells resistant to FLT3 inhibition. We found that E6201 exerted profound apoptogenic effects on AML cells harboring resistance-conferring FLT3 mutations. This activity appeared to be p53 dependent, and E6201-induced cytotoxicity was retained under hypoxic culture conditions and during coculture with mesenchymal stem cells that mimic the AML microenvironment. Furthermore, E6201 markedly reduced leukemia burden and improved the survival of mice in a human FLT3-mutated AML model. Collectively, our data provide a preclinical basis for the clinical evaluation of E6201 in AML patients harboring FLT3 mutations, including those who relapse following FLT3-targeted monotherapy. PMID- 26822156 TI - Can Economic Performance Predict Pediatric Surgical Capacity in Sub-Saharan Africa? AB - BACKGROUND: The relationship between economic status and pediatric surgical capacity in low- and middle-income countries (LMICs) is poorly understood. In sub Saharan Africa (SSA), Nigeria accounts for 20 % of the population and has the highest Gross Domestic Product (GDP), but whether this economic advantage translates to increased pediatric surgical capacity is unknown. This study compares the pediatric surgical capacity between Nigeria and other countries within the region. METHODS: The Pediatric Personnel, Infrastructure, Procedures, Equipment and Supplies (PediPIPES) survey, a recent tool that is useful in assessing and comparing the capacity of health facilities to deliver essential and emergency surgical care (EESC) to children in LMICs, was used for this evaluation. RESULTS: Data from hospitals in Nigeria (n = 24) and hospitals in 17 other sub-Saharan African countries (n = 25) were compared. The GDP of Nigeria was approximately twenty-five times the average GDP of the 17 other countries represented in our survey. Running water was unavailable in 58 % of the hospitals in Nigeria compared to 20 % of the hospitals in the other countries. Most hospitals in Nigeria and in the other countries did not have a CT scan (67 and 60 %, respectively). Endoscopes were unavailable in 58 % of the hospitals in Nigeria and 44 % of the hospitals in the other countries. CONCLUSIONS: Despite better economic indicators in Nigeria, there were no distinct advantages over the other countries in the ability to deliver EESC to children. Our findings highlighted the urgent need for specific allocation of more resources to pediatric surgical capacity building efforts across the entire region. PMID- 26822157 TI - Surgical Treatment of NEN of Small Bowel: A Retrospective Analysis. AB - BACKGROUND: Neuroendocrine Neoplasms of the small intestine have been noticed more frequently over the past 35 years. They constitute about 25% of all NENs and 29% of all tumors of the small intestine. Due to the predominantly indolent nature and overall good prognosis, the benefit of surgical treatment is still debated. METHODS: In a retrospective study, data of 83 surgically treated patients with neuroendocrine neoplasms of the small intestine, 48 males and 35 females with a median age of 62 years (range 25-86 years) were analyzed. Patient data were documented in the MaDoc database for neuroendocrine tumors of the University Medical Center of Mainz. IBM SPSS Statistics 20 was used for statistical analysis. Kaplan-Meier survival curves and Log-Rank tests, censoring patients at the time of last follow-up, were used to compare the overall survival depending on potential prognostic factors (stage, grade, surgical treatment). RESULTS: At the time of diagnoses, the most common clinical symptoms were abdominal pain (n = 31, 37.3%), bowel obstruction (n = 11, 13.3%), bowel perforation and peritonitis (n = 3, 3.6%), gastrointestinal bleeding (n = 9, 10.8%), weight loss (n = 11, 13.3%), and carcinoid syndrome (n = 27, 32.5%). 65 patients (78.3%) had lymph node metastasis and in 58 patients (69.9%) distant metastasis were present. Segmental bowel resection (44) was the most common surgical procedure, followed by right hemi-colectomy (32) and explorative laparotomy (7). In most patients (78.9%), lymphadenectomy (systematic/selective) was performed. The 5-year survival of patients who underwent a systematic or a selective lymphadenectomy differed significantly (82.2 vs. 40.0%). The overall 3 , 5-, and 10-year survival rates were 88.2, 80.3, and 71.0%, respectively. CONCLUSION: Mesenteric lymph node metastases are almost invariably present and have significant impact on patients' prognosis. Systematic lymphadenectomy prevents complications and improves the survival. Early surgical treatment should be the goal in order to prevent complications. PMID- 26822158 TI - Anesthesia Care Capacity at Health Facilities in 22 Low- and Middle-Income Countries. AB - BACKGROUND: Globally, an estimated 2 billion people lack access to surgical and anesthesia care. We sought to pool results of anesthesia care capacity assessments in low- and middle-income countries (LMICs) to identify patterns of deficits and provide useful targets for advocacy and intervention. METHODS: A systematic review of PubMed, Cochrane Database of Systematic Reviews, and Google Scholar identified reports that documented anesthesia care capacity from LMICs. When multiple assessments from one country were identified, only the study with the most facilities assessed was included. Patterns of availability or deficit were described. RESULTS: We identified 22 LMICs (15 low- and 8 middle-income countries) with anesthesia care capacity assessments (614 facilities assessed). Anesthesia care resources were often unavailable, including relatively low-cost ones (e.g., oxygen and airway supplies). Capacity varied markedly between and within countries, regardless of the national income. The availability of fundamental resources for safe anesthesia, such as airway supplies and functional pulse oximeters, was often not reported (72 and 36 % of hospitals assessed, respectively). Anesthesia machines and the capability to perform general anesthesia were unavailable in 43 % (132/307 hospitals) and 56 % (202/361) of hospitals, respectively. CONCLUSION: We identified a pattern of critical deficiencies in anesthesia care capacity in LMICs, including some low-cost, high value added resources. The global health community should advocate for improvements in anesthesia care capacity and the potential benefits of doing so to health system planners. In addition, better quality data on anesthesia care capacity can improve advocacy, as well as the monitoring and evaluation of changes over time and the impact of capacity improvement interventions. PMID- 26822159 TI - Direct flow cytometry measurements reveal a fine-tuning of symbiotic cell dynamics according to the host developmental needs in aphid symbiosis. AB - Endosymbiotic associations constitute a driving force in the ecological and evolutionary diversification of metazoan organisms. Little is known about whether and how symbiotic cells are coordinated according to host physiology. Here, we use the nutritional symbiosis between the insect pest, Acyrthosiphon pisum, and its obligate symbiont, Buchnera aphidicola, as a model system. We have developed a novel approach for unculturable bacteria, based on flow cytometry, and used this method to estimate the absolute numbers of symbionts at key stages of aphid life. The endosymbiont population increases exponentially throughout nymphal development, showing a growing rate which has never been characterized by indirect molecular techniques. Using histology and imaging techniques, we have shown that the endosymbiont-bearing cells (bacteriocytes) increase significantly in number and size during the nymphal development, and clustering in the insect abdomen. Once adulthood is reached and the laying period has begun, the dynamics of symbiont and host cells is reversed: the number of endosymbionts decreases progressively and the bacteriocyte structure degenerates during insect aging. In summary, these results show a coordination of the cellular dynamics between bacteriocytes and primary symbionts and reveal a fine-tuning of aphid symbiotic cells to the nutritional demand imposed by the host physiology throughout development. PMID- 26822161 TI - Ru alkylidene compounds bearing tridentate, dianionic ligands: Lewis acid activation and olefin metathesis. AB - The series of tridentate complexes of Ru-alkylidenes (L)Ru(CHPh)(SCH2CH2)2E (E = O, L = SIMes 1, PCy3 2, E = S, L = SIMes 3, PCy3 4; E = PPh 7, L = PCy3), (L)Ru(CHPh)(SC6H4)2S (L = SIMes 5, PCy3 6), (L)Ru(CHPh) (OCH2CH2)2O (L = SIMes 8, PCy3 9) were prepared and shown to react with one equivalent of BCl3 to give the complexes (L)Ru(CHPh)Cl[E(CH2CH2S)2BCl2] (E = O, L = SIMes 10, PCy3 11, E = S, L = SIMes 12a/b, PCy3 13, E = PPh, L = PCy3 16) and (L)Ru(CHPh)(SC6H4)2O (L = SIMes 14, PCy3 15). In the case of 1 and 2 reaction with two equivalents of BCl3 affording the corresponding cation via chloride abstraction. These cations coordinate MeCN to give the six coordinate Ru cation salts [(L)Ru(CHPh)- (NCMe)(O(CH2CH2S)2BCl2)][BCl4] L = SIMes 17, PCy3 18). The generated five coordinate cations derived from 2-9 via addition of two equivalents of BCl3 were evaluated in standard preliminary tests for olefin metathesis catalysis. PMID- 26822160 TI - Impact of the introduction of EBUS on time to management decision, complications, and invasive modalities used to diagnose and stage lung cancer: a pragmatic pre post study. AB - BACKGROUND: Utilisation of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and guide sheath (EBUS-GS) for diagnosis and staging of lung cancer is gaining popularity, however, its impact on clinical practice is unclear. This study aimed to determine the impact of the introduction of endobronchial ultrasound-guided procedures (EBUS) on time to management decision for lung cancer patients, and on the utilisation of other invasive diagnostic modalities, including CT-guided trans-thoracic needle aspiration (CT-TTNA), bronchoscopy, and mediastinoscopy. METHODS: Hospital records of new primary lung cancer patients presenting in 2007 and 2008 (Pre-EBUS cohort) and in 2010 and 2011 (Post-EBUS cohort) were reviewed retrospectively. RESULTS: The Pre-EBUS cohort included 234 patients. Of the 326 patients in the Post-EBUS cohort, 90 had an EBUS procedure (EBUS-TBNA for 19.0% and EBUS-GS for 10.4% of cases). The number of CT-TTNAs and bronchoscopies decreased following the introduction of EBUS (p = 0.015 and p < 0.001 respectively). Of 162 CT-TTNAs, 59 (36%) resulted in complications compared to 1 complication each for bronchoscopy and EBUS-GS, and no complications from EBUS-TBNA. Fewer complications occurred overall in the Post-EBUS cohort compared to the Pre-EBUS cohort (p = 0.0264). The median time to management decision was 17 days (IQR 24) for the Pre-EBUS and 13 days (IQR 21) for the Post-EBUS cohort (p = 0.07). Within the Post-EBUS cohort, median time to management decision was longer for the EBUS group (n = 90) than the Non-EBUS group (17 days (IQR 29) vs. 10 days (IQR 10), p < 0.001). For half of EBUS-TBNA patients (n = 28, 50.0%) and EBUS-GS patients (n = 14, 50.0 %), EBUS alone provided sufficient diagnostic and/or staging information; these patients had median time to management decision of 10 days. Regression analysis revealed that the number of imaging events, inpatient, and outpatient visits were significant predictors of time to management decision of >28 days; EBUS was not a predictor of time to management decision. CONCLUSIONS: The introduction of EBUS led to fewer CT-TTNAs and bronchoscopies and did not impact on the time to management decision. EBUS-TBNA or EBUS-GS alone provided sufficient information for diagnosis and/or regional staging in half of the lung cancer patients referred for this investigation. PMID- 26822162 TI - Increasing the frequency of physical activity very brief advice for cancer patients. Development of an intervention using the behaviour change wheel. AB - BACKGROUND: Being physically active has multiple benefits for cancer patients. Despite this only 23% are active to the national recommendations and 31% are completely inactive. A cancer diagnosis offers a teachable moment in which patients might be more receptive to lifestyle changes. Nurses are well placed to offer physical activity advice, however, only 9% of UK nurses involved in cancer care talk to all cancer patients about physical activity. A change in the behaviour of nurses is needed to routinely deliver physical activity advice to cancer patients. As recommended by the Medical Research Council, behavioural change interventions should be evidenced-based and use a relevant and coherent theoretical framework to stand the best chance of success. OBJECTIVE: This paper presents a case study on the development of an intervention to improve the frequency of delivery of very brief advice (VBA) on physical activity by nurses to cancer patients, using the Behaviour Change Wheel (BCW). METHOD: The eight composite steps outlined by the BCW guided the intervention development process. An iterative approach was taken involving key stakeholders (n = 45), with four iterations completed in total. This was not defined a priori but emerged during the development process. RESULTS: A 60 min training intervention, delivered in either a face-to-face or online setting, with follow-up at eight weeks, was designed to improve the capability, opportunity and motivation of nurses to deliver VBA on physical activity to people living with cancer. This intervention incorporates seven behaviour change techniques of goal setting coupled with commitment; instructions on how to perform the behaviour; salience of the consequences of delivering VBA; a demonstration on how to give VBA, all delivered via a credible source with objects added to the environment to support behavioural change. CONCLUSION: The BCW is a time consuming process, however, it provides a useful and comprehensive framework for intervention development and greater control over intervention replication and evaluation. PMID- 26822163 TI - Syntheses and biological activities of deoxy-d-allose fatty acid ester analogs. AB - We describe the syntheses of three different deoxy-D-allose analogs [2-deoxy-d allose (2-DOAll), 1,2-dideoxy-d-allose (1,2-DOAll), and 1,2-didehydro-1,2-dideoxy d-allose (1,2-DHAll)] and their fatty acid esters via regioselective lipase catalyzed transesterification. Among them, 2-DOAll and its decanoate (2-DOAll C10) showed higher inhibitory activity on plant growth, which is similar to d allose (All) [corrected] and its decanoate (All-C10). Bioassay results of deoxy All-C10 on four plant species suggest that the hydroxy group at the C-1 position might be important showing growth inhibitory activity. In addition, co-addition of gibberellin (GA3) with 1,2-DHAll-C10 and 2-DOAll-C10 recovered plant growth, suggesting that they might mainly inhibit biosynthesis of gibberellin. PMID- 26822164 TI - Copper-catalyzed oxidative [2+2+1] annulation of 1,n-enynes with alpha-carbonyl alkyl bromides through C-Br/C-H functionalization. AB - The Cu-catalyzed oxidative [2+2+1] annulation of 1,n-enynes (n = 6, 7) with alpha carbonyl alkyl bromides through C-Br/C-H functionalization has been developed. Using Ag2CO3/tert-butyl hydroperoxide (TBHP) as co-oxidants, alpha-carbonyl alkyl bromides provide two bonds, the alpha-C(sp(3))-Br bonds and the alpha-C(sp(3))-H bonds, to cyclize with the 1,n-enynes and Cu(MeCN)4PF6, thus forming three new C C bonds and two rings in a single reaction. PMID- 26822165 TI - An exploratory study into the effects of a 20 minute crushed ice application on knee joint position sense during a small knee bend. AB - OBJECTIVES: The effect of cryotherapy on joint positioning presents conflicting debates as to whether individuals are at an increased risk of injury when returning to play or activity immediately following cryotherapy application at the knee. The aim of this study was to investigate whether a 20 min application of crushed ice at the knee immediately affects knee joint position sense during a small knee bend. DESIGN: Pre- and post-intervention. SETTING: University movement analysis laboratory. PARTICIPANTS: Eleven healthy male participants. MAIN OUTCOME MEASURES: Kinematics of the knee were measured during a weight bearing functional task pre and post cryotherapy intervention using three-dimensional motion analysis (Qualisys Medical AB Gothenburg, Sweden). Tissue cooling was measured via a digital thermometer at the knee. RESULTS: Results demonstrated significant reductions in the ability to accurately replicate knee joint positioning in both sagittal (P = .035) and coronal (P = .011) planes during the descent phase of a small knee bend following cryotherapy. CONCLUSION: In conclusion a 20 min application of crushed ice to the knee has an adverse effect on knee joint repositioning. Team doctors, clinicians, therapists and athletes should consider these findings when deciding to return an athlete to functional weight bearing tasks immediately following ice application at the knee, due to the potential increase risk of injury. PMID- 26822166 TI - Polymer-Ion Interaction Weakens the Strain-Rate Dependence of Extension-Induced Crystallization for Poly(ethylene oxide). AB - The crystallization of poly(ethylene oxide) (PEO)-sodium iodine (NaI) composites is investigated by differential scanning calorimetry (DSC), extensional rheology, and in situ small-angle X-ray scattering (SAXS) with the aim of demonstrating versatile roles played by polymer-ion interactions. In the isothermal quiescent crystallization process, a decrease in the crystal growth rate is observed for PEO-NaI and is attributed to slow chain movement caused by the coordination between cations and polymer. In situ SAXS on extensional flow-induced crystallization (FIC) exhibits enhanced kinetics and orientation for both PEO and PEO-NaI with increasing strain rate. However, an overall weaker strain-rate dependence of FIC is observed for PEO-NaI, which can be interpreted as a synergistic consequence of promoted nucleation under flow and impeded crystal growth by polymer-ion interaction. A possible microscopic mechanism is proposed to account for the experimental observation based on the formation of transient cross-linking points in PEO-NaI and their influence on the entanglement network of polymer under various flow fields. The disclosed strain-rate dependence and various ion effects on the behavior of PEO-salt composites contribute to a comprehensive understanding of polymer-ion solid polyelectrolytes. PMID- 26822167 TI - Using Inorganic Nanomaterials to Endow Biocatalytic Systems with Unique Features. AB - The rapid growth in nanotechnology and biotechnology offers a wealth of opportunities for the combination of natural enzymes with different kinds of nanomaterial. Here, we highlight recent advances in constructing nanomaterial incorporated enzymes that integrate the specific recognition and biocatalytic properties of enzymes with the attractive electronic, optical, magnetic, and catalytic properties of nanomaterials. These composite materials have some extra features that are not possessed by the enzymes themselves, such as electron transfer mediated by nanoparticles, enzyme delivery, remote activation and/or deactivation of enzymatic activity, and fabrication of catalytic entities with complementary functions. Additionally, we describe briefly the current challenges and future development of unique enzyme-nanomaterial hybrid systems. We hope that this review will help to accelerate further progress in this promising field. PMID- 26822168 TI - Usefulness of Intravascular Ultrasound for Predicting Risk of Intraprocedural Stent Thrombosis. AB - Intraprocedural stent thrombosis (IPST) is a rare complication of percutaneous coronary intervention that leads to poor outcomes; however, the factors contributing to IPST remain largely unknown. Accordingly, we used intravascular ultrasound (IVUS) to examine the lesion characteristics in patients with IPST. We retrospectively analyzed 1,504 consecutive stent-implanted lesions in 1,324 patients (326 with ST-segment elevation myocardial infarction [STEMI], 403 patients with non-ST-segment elevation acute coronary syndrome [NSTE-ACS], and 595 patients with stable angina). Of these, IPST occurred in 5 patients during percutaneous coronary intervention (0.4% per patient; 3 with STEMI, 2 with NSTE ACS). The IVUS characteristics of plaques that developed IPST were compared with those of controls without the evidence of IPST (non-IPST; n = 15) who were matched by age, gender, lesion location, and clinical presentation (STEMI, NSTE ACS, or stable angina). All 5 lesions that led to IPST had ruptured plaques with positive remodeling and attenuation. Plaque rupture was also observed in 40% of the non-IPST group. Multiple plaque ruptures in the culprit lesion were more common in the IPST group (80% vs 7%; p <0.01). The maximum cavity area was larger in the IPST group than in the non-IPST group having plaque rupture (4.6 mm(2) [interquartile range, 4.3 to 6.5] vs 2.4 mm(2) [1.8 to 2.9]; p <0.01). In conclusion, we found using IVUS that multiple plaque ruptures with larger cavities more often evolved into IPST. PMID- 26822169 TI - Congenital Panfollicular Nevus in a 6-Month-Old Girl. AB - A 6-month-old girl presented with an irregular nodule on the right lateral neck. The lesion, which superficially resembled a lymphangioma or mastocytoma, had been present since birth but had recently been growing. The patient was referred for surgical resection. Microscopic findings were compatible with a recently described rare hamartoma termed "panfollicular nevus," which is a well circumscribed lesion containing aberrantly differentiated, clustered hair follicles in high density. PMID- 26822170 TI - Validation of FoodChekTM - Salmonella for Rapid Detection of Salmonella in Eggs, Derivative Products, and the Environment. AB - The FoodChekTM - Salmonella assay is an immunomagnetic lateral flow assay for the rapid detection (shorter than 24 h) of the most frequently isolated Salmonella (groups B-E) in eggs, egg-derivative products, and environmental surfaces. The FoodChek - Salmonella assay correctly identified 99.6% (239/240) of the samples tested in the matrix studied, and the statistical analysis of the method comparison study results demonstrated that it performs as well as U.S. culture based reference methods. Ninety-nine percent of the 103 Salmonella strains tested belonging to serogroups B-E were detected during the inclusivity study. Concerning the exclusivity, 31 nontarget strains were tested. No cross-reactivity was observed in FoodChek - Salmonella assay enrichment conditions. In addition, the assay shows strong robustness, good stability, and consistency among lots. The present study proves that the assay is an effective tool for the rapid detection of Salmonella spp. in whole liquid eggs, liquid egg white (liquid egg albumen), shell eggs, dried whole eggs, dried egg yolks, and environmental surfaces as stainless steel, plastic, rubber, ceramic tiles, and sealed concrete. PMID- 26822173 TI - Design and Syntheses of Three Novel Carbonate Halides: Cs3 Pb2 (CO3 )3 I, KBa2 (CO3 )2 F, and RbBa2 (CO3 )2 F. AB - Three new carbonate halides, Cs3 Pb2 (CO3 )3 I, KBa2 (CO3 )2 F and RbBa2 (CO3 )2 F have been synthesized with hydrothermal and solid-state methods. Cs3 Pb2 (CO3 )3 I is the first product in the lead carbonate iodides family; KBa2 (CO3 )2 F and RbBa2 (CO3 )2 F are the first two centrosymmetric compounds found in the alkaline-alkaline earth carbonate fluorides family. Cs3 Pb2 (CO3 )3 I crystallizes in a centrosymmetric space group C2/m, and exhibits a two- dimensional layered structure which is formed by [Cs4 Pb4 (CO3 )6 I2 ]infinity double-layers consisting of [Pb2 (CO3 )3 I]infinity single-layers bridged by the Cs atoms. KBa2 (CO3 )2 F and RbBa2 (CO3 )2 F, which are isostructural, crystallize in a trigonal crystal system with a centric space group of R3? featuring a honeycomb-like framework. First principle calculations indicate that Cs3 Pb2 (CO3 )3 I has a moderate birefringence and explain the difference between the band gaps of the title compounds from electron structures. The effects of cations and halogens on the structures and properties of the title compounds are also discussed. PMID- 26822172 TI - Safety of a Four-factor Prothrombin Complex Concentrate Versus Plasma for Vitamin K Antagonist Reversal: An Integrated Analysis of Two Phase IIIb Clinical Trials. AB - OBJECTIVES: Clinicians often need to rapidly reverse vitamin K antagonists (VKAs) in the setting of major hemorrhage or urgent need for surgery. Little is known about the safety profile of the traditional reversal agent, plasma, or the newly approved agent, four-factor prothrombin complex concentrate (4F-PCC), in a randomized setting. This is an integrated analysis of safety data from two clinical trials that evaluated 4F-PCC versus plasma for the treatment of patients requiring rapid VKA reversal for acute major bleeding or prior to an urgent surgical/invasive procedure. METHODS: This descriptive analysis comprised adverse event (AE) data from two phase IIIb, randomized, controlled trials. The bleeding and surgical studies were performed across 36 and 33 sites, respectively, in nine countries, with the integrated analysis comprising 388 patients (4F-PCC, n = 191; plasma, n = 197) aged >= 18 years, who required VKA reversal due to major bleeding or prior to an urgent surgical/invasive procedure. Patients received either 4F-PCC, containing nonactivated factors II, VII, IX, and X and proteins C and S (Beriplex/Kcentra, CSL Behring) or plasma, both dosed according to baseline international normalized ratio and body weight. Patients were also to receive vitamin K1. AEs and serious AEs (SAEs) were assessed up to days 10 and 45, respectively. RESULTS: The proportion of patients with AEs (4F-PCC, 115/191 [60.2%]; plasma, 124/197 [62.9%]) and SAEs (4F-PCC, 54/191 [28.3%]; plasma, 49/197 [24.9%]) was similar between groups. The proportion of patients with thromboembolic events was also similar between groups (4F-PCC, 14/191 [7.3%]; plasma, 14/197 [7.1%]). There were 13 (6.8%) deaths in the 4F-PCC group and 13 (6.6%) in the plasma group. Fluid overload events occurred in more patients in the plasma group than the 4F-PCC group (25 [12.7%] and 9 [4.7%], respectively). CONCLUSIONS: These safety data represent the largest controlled assessment of a 4F-PCC to date. For patients requiring urgent VKA reversal, 4F-PCC had a safety profile similar to that of plasma (AEs, SAEs, thromboembolic events, and deaths), but was associated with fewer fluid overload events. PMID- 26822174 TI - Phenethyl isothiocyanate enhances TRAIL-induced apoptosis in oral cancer cells and xenografts. AB - OBJECTIVES: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been regarded as a promising candidate for cancer therapy. However, most of oral cancer cell lines are resistant to the TRAIL-induced cytotoxicity. The aim of this study was to investigate the ability of phenethyl isothiocyanate (PEITC) to sensitize TRAIL-induced apoptosis in TRAIL-resistant oral cancer cells and xenografts. MATERIALS AND METHODS: Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, Western blotting, and a mouse xenograft model were used to study the effects of PEITC and TRAIL on two TRAIL-resistant human oral cancer cells, SAS and Ca9-22. RESULTS: PEITC upregulated death receptor 4 (DR4) and DR5 protein expression and increased reactive oxygen species (ROS) production in both SAS and Ca9-22 cells. Antioxidant N-acetyl-L-cysteine (NAC) and c-Jun NH2 terminal kinase (JNK) inhibitor SP600125 inhibited PEITC-induced DR4 and DR5 expression. Inhibitor experiments showed that PEITC induced apoptosis through ROS mediated JNK activation and upregulation of DR4 and DR5. Furthermore, treatment with PEITC significantly increased TRAIL-induced apoptosis in both cells. Combined treatment with PEITC and TRAIL had greater effect on the inhibition of tumor growth than either agent alone. CONCLUSIONS: We showed for the first time that PEITC overcomes TRAIL resistance in oral cancer cells and enhance the therapeutic potential of TRAIL in vivo. CLINICAL RELEVANCE: PEITC, either alone or in combination with TRAIL, can be used as a new therapeutic approach for the treatment of oral cancers. PMID- 26822175 TI - External Versus Internal Pancreatic Duct Drainage for the Early Efficacy After Pancreaticoduodenectomy: A Retrospectively Comparative Study. AB - PURPOSE: To compare the early efficacy of external versus internal pancreatic duct drainage after pancreaticoduodenectomy (PD), providing clinical evidence for selecting the optimal approach to pancreatic duct drainage. MATERIAL AND METHODS: The clinical data of 395 consecutive patients undergoing PD from 2006 to 2013 were analyzed retrospectively. All the patients were divided into external and internal drainage group. Intraoperative blood loss, surgery duration, postoperative hospitalization duration, mortality rate, PF, and other complications were compared between the two groups. The perioperative relative risk factors that might induce PF were analyzed. RESULTS: External drainage significantly reduced the incidences of post-PD PF, delayed gastric emptying, abdominal infection, bowel obstruction, overall complications, and shortened the healing time of PF (p < .05). The univariate analysis showed that the pancreatic duct drainage method, body mass index (BMI), preoperative serum bilirubin level, perioperative blood transfusion, pancreaticojejunostomy approach, pancreatic texture, pancreatic duct diameter, and primary disease differed markedly between the two groups (p < .05). A multivariate analysis revealed that BMI >= 25 kg/m(2), internal pancreatic duct drainage, pancreatic duct diameter <3 mm, soft pancreatic texture, and ampullary disease were independent risk factors for PF. CONCLUSIONS: External pancreatic duct drainage can effectively reduce the morbidity of PF and overall complications after PD. PMID- 26822176 TI - Self-Restoration of Superhydrophobicity on Shape Memory Polymer Arrays with Both Crushed Microstructure and Damaged Surface Chemistry. AB - Recently, self-healing superhydrophobic surfaces have become a new research focus due to their recoverable wetting performances and wide applications. However, until now, on almost all reported surfaces, only one factor (surface chemistry or microstructure) can be restored. In this paper, a new superhydrophobic surface with self-healing ability in both crushed microstructure and damaged surface chemistry is prepared by creating lotus-leaves-like microstructure on the epoxy shape memory polymer (SMP). Through a simple heating process, the crushed surface microstructure, the damaged surface chemistry, and the surface superhydrophobicity that are destroyed under the external pressure and/or O2 plasma action can be recovered, demonstrating that the obtained superhydrophobic surface has a good self-healing ability in both of the two factors that govern the surface wettability. The special self-healing ability is ascribed to the good shape memory effect of the polymer and the reorganization effect of surface molecules. This paper reports the first use of SMP material to demonstrate the self-healing ability of surface superhydrophobicity, which opens up some new perspectives in designing self-healing superhydrophobic surfaces. Given the properties of this surface, it could be used in many applications, such as self cleaning coatings, microfluidic devices, and biodetection. PMID- 26822177 TI - A Caenorhabditis elegans Homologue of LYST Functions in Endosome and Lysosome Related Organelle Biogenesis. AB - LYST-1 is a Caenorhabditis elegans BEACH domain containing protein (BDCP) homologous to LYST and NBEAL2, BDCPs controlling organelle biogenesis that are implicated in human disease. Unlike the three other BDCPs encoded by C. elegans, mutations in lyst-1 lead to smaller lysosome-related organelles (LROs), smaller lysosomes, increased numbers of LROs and decreased numbers of early endosomes. lyst-1(-) mutations do not obviously disrupt protein trafficking to lysosomes or LROs, however, the formation of gut granules is diminished. PMID- 26822179 TI - Modeling Relationships Between Two Categorical Variables When Data Are Missing: Examining Consequences of the Missing Data Mechanism in an HIV Data Set. AB - Analysts evaluating the strengths of relationships between variables in behavioral science research must often contend with the problem of missing data. Analyses are typically performed using data for cases that are either complete in all the variables, or assume that the data are missing at random. Often, these approaches yield biased results. Using empirical data, the current work explores the implications and consequences of using various statistical models to describe the association of two variables, one ordinal and one dichotomous, in which data are incomplete for the dichotomous variable. These models explicitly reflect the missing data mechanism; models that hypothesize nonignorable nonresponse are given particular attention. Both the statistical fit and substantive consequences of these models are examined. This new methodological approach to examining nonignorable nonresponse can be applied to many behavioral science data sets containing an ordinal variable. PMID- 26822178 TI - Covalent immobilization of stem cell inducing/recruiting factor and heparin on cell-free small-diameter vascular graft for accelerated in situ tissue regeneration. AB - The development of cell-free vascular grafts has tremendous potential for tissue engineering. However, thrombus formation, less-than-ideal cell infiltration, and a lack of growth potential limit the application of electrospun scaffolds for in situ tissue-engineered vasculature. To overcome these challenges, here we present development of an acellular tissue-engineered vessel based on electrospun poly(L lactide-co-E-caprolactone) scaffolds. Heparin was conjugated to suppress thrombogenic responses, and substance P (SP) was immobilized to recruit host cells. SP was released in a sustained manner from scaffolds and recruited human bone marrow-derived mesenchymal stem cells. The biocompatibility and biological performance of the grafts were evaluated by in vivo experiments involving subcutaneous scaffold implantation in Sprague-Dawley rats (n = 12) for up to 4 weeks. Histological analysis revealed a higher extent of accumulative host cell infiltration, neotissue formation, collagen deposition, and elastin deposition in scaffolds containing either SP or heparin/SP than in the control groups. We also observed the presence of a large number of laminin-positive blood vessels, von Willebrand factor (vWF(+) ) cells, and alpha smooth muscle actin-positive cells in the explants containing SP and heparin/SP. Additionally, SP and heparin/SP grafts showed the existence of CD90(+) and CD105(+) MSCs and induced a large number of M2 macrophages to infiltrate the graft wall compared with that observed with the control group. Our cell-free grafts could enhance vascular regeneration by endogenous cell recruitment and by mediating macrophage polarization into the M2 phenotype, suggesting that these constructs may be a promising cell-free graft candidate and are worthy of further in vivo evaluation. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1352-1371, 2016. PMID- 26822180 TI - Cluster Analysis as a Method of Recovering Types of Intraindividual Growth Trajectories: A Monte Carlo Study. AB - There has been increased interest in and application of cluster analysis in longitudinal applications to identify distinctive developmental patterns of intraindividual change. This article used Monte Carlo experiments to evaluate the adequacy of cluster analysis to recover group membership based on simulated latent growth curve (LGC) models. The simulated LGC models were manipulated by varying growth parameters (e.g., elevation, dispersion, and shape) for subpopulation growth curves (e.g., linear and quadratic growth models). The evaluation of cluster analysis to recover individual membership in these growth curve subpopulations was completed via the Kappa statistics. Cluster analysis failed to recover adequately growth subtypes when the difference between growth curves was shape only. It was much more successful when the distance between initial mean levels was large (e.g., difference of two standard deviations), independent of difference in the shape of the growth curves. Tentative guidelines were proposed to facilitate the evaluation of the adequacy of a cluster analytic solution to recover subtype heterogeneity in longitudinal (intraindividual) growth curves. PMID- 26822181 TI - Fitting Item Response Theory Models to Two Personality Inventories: Issues and Insights. AB - The present study compared the fit of several IRT models to two personality assessment instruments. Data from 13,059 individuals responding to the US-English version of the Fifth Edition of the Sixteen Personality Factor Questionnaire (16PF) and 1,770 individuals responding to Goldberg's 50 item Big Five Personality measure were analyzed. Various issues pertaining to the fit of the IRT models to personality data were considered. We examined two of the most popular parametric models designed for dichotomously scored items (i.e., the two- and three-parameter logistic models) and a parametric model for polytomous items (Samejima's graded response model). Also examined were Levine's nonparametric maximum likelihood formula scoring models for dichotomous and polytomous data, which were previously found to provide good fits to several cognitive ability tests (Drasgow, Levine, Tsien, Williams, & Mead, 1995). The two- and three parameter logistic models fit some scales reasonably well but not others; the graded response model generally did not fit well. The nonparametric formula scoring models provided the best fit of the models considered. Several implications of these findings for personality measurement and personnel selection were described. PMID- 26822182 TI - Confirmatory Latent Class Analysis: Model Selection Using Bayes Factors and (Pseudo) Likelihood Ratio Statistics. AB - Inequality constraints among class specific probabilities can be used to assign a specific meaning to the classes in a latent class model. Different models arise if different sets of constraints are used. In this paper, model selection using Bayes factors, and, (pseudo) likelihood ratio statistics evaluated using posterior predictive p-values, will be discussed. It will be illustrated that these Bayesian selection criteria do not suffer from the same flaw as maximum likelihood based selection criteria. Using a small simulation study it will be shown that, in the context of the simulation study, Bayes factors and the pseudo likelihood ratio statistic have the best proporties. The article will be concluded with an example. PMID- 26822183 TI - Differentiation of Cognitive Abilities as a Function of Level of General Intelligence: A Latent Variable Approach. AB - Differentiation of cognitive abilities at different levels of general ability in same-aged subjects was tested by a latent variable approach in a multiple-groups design. Eighteen-year old conscripts (n = 14,720) representing the whole range of general ability in the male population, except for the mentally retarded, were tested by the Swedish Enlistment Battery. The sample of subjects was divided into 8, 16 and 32 groups according to level of general ability (G), and the amount of variance due to the ability factors Crystallized intelligence (Gc) and General visualization (Gv) was studied over the G levels. Variance contributed by Gc and Gv increased as the level of G increased. This effect was, however, not observed up through the highest levels of G, probably due to deficiencies in the measurement properties of the Gc and Gv tests at the highest G levels. Theoretical and methodological implications of the results are discussed, as are the consequences for the assessment of specific cognitive abilities at different levels of general ability. PMID- 26822184 TI - Sample Size in Factor Analysis: The Role of Model Error. AB - This article examines effects of sample size and other design features on correspondence between factors obtained from analysis of sample data and those present in the population from which the samples were drawn. We extend earlier work on this question by examining these phenomena in the situation in which the common factor model does not hold exactly in the population. We present a theoretical framework for representing such lack of fit and examine its implications in the population and sample. Based on this approach we hypothesize that lack of fit of the model in the population will not, on the average, influence recovery of population factors in analysis of sample data, regardless of degree of model error and regardless of sample size. Rather, such recovery will be affected only by phenomena related to sampling error which have been studied previously. These hypotheses are investigated and verified in two sampling studies, one using artificial data and one using empirical data. PMID- 26822185 TI - Hypothesis Testing and Model Comparison in Two-level Structural Equation Models. AB - One basic and important problem in two-level structural equation modeling is to find a good model for the observed sample data. This article demonstrates the use of the well-known Bayes factor in the Bayesian literature for hypothesis testing and model comparison in general two-level structural equation models. It is shown that the proposed methodology is flexible, and can be applied to situations with a wide variety of nonnested models. Moreover, some problems encountered in using existing methods for goodness-of-fit assessment of the proposed model can be alleviated. An illustrative example with some real data from an AIDS care study is presented. PMID- 26822186 TI - A functional temporal association mining approach for screening potential drug drug interactions from electronic patient databases. AB - AIMS: Drug-drug interactions (DDIs) can result in serious consequences, including death. Existing methods for identifying potential DDIs in post-marketing surveillance primarily rely on spontaneous reports. These methods suffer from severe underreporting, incompleteness, and various bias. The aim of this study was to more effectively screen potential DDIs using patient electronic data and temporal association mining techniques. METHODS: We focus on discovery of potential DDIs by analyzing the temporal relationships between the concurrent use of two drugs of interest and the occurrences of various symptoms. We introduced innovative functional temporal association rules where the degree of temporal association between two events within a patient case was defined by a function. RESULTS: Preliminary test results on two drug pairs (i.e., and ) were classified into 260 clinically meaningful categories. These categories were evaluated by physicians and the results exhibited that all the potential DDIs were confined to top 20 of the 260 outcomes. CONCLUSIONS: Our methodology can be used to dramatically reduce a long list of association rules to a manageable list for further analysis and investigation by drug safety professionals. PMID- 26822187 TI - Early experience with endoscopic lumbar sympathectomy for plantar hyperhidrosis. AB - OBJECTIVE: We describe our endoscopic lumbar sympathectomy technique and our early experience using it to treat plantar hyperhidrosis. METHODS: We reviewed 20 lumbar sympathectomies performed in our vascular unit for plantar hyperhidrosis in 10 patients from 2011 and 2014. Demographics and outcomes were analyzed and a review of the literature conducted. RESULTS: All procedures were carried out endoscopically with no intraoperative or postoperative morbidity. Plantar anhidrosis was achieved in all the patients, although two patients (20%) suffered a relapse. Unwanted side-effects occurred in the form of compensatory sweating in three patients (30%) and post-sympathectomy neuralgia in two patients (20%). None of the patients experienced sexual dysfunction. CONCLUSION: Management of plantar hyperhidrosis may be based upon a therapeutic ladder starting with conservative measures and working up to surgery depending on the severity of the disease. Minimally invasive (endoscopic) sympathectomy for the thoracic chain is well established, but minimally invasive sympathectomy for the lumbar chain is a relatively new technique. Endoscopic lumbar sympathectomy provides an effective, minimally invasive method of surgical management, but long-term data are lacking. PMID- 26822188 TI - Chiral Phosphoric Acid Catalyzed Kinetic Resolution of Indolines Based on a Self Redox Reaction. AB - A strategy for oxidative kinetic resolution of racemic indolines was developed, employing salicylaldehyde derivative as the pre-resolving reagent and chiral phosphoric acid as the catalyst. The iminium intermediate, formed by the condensation reaction of an enantiomer of indoline with salicylaldehyde derivative, was hydrogenated by the same enantiomer of indoline to afford another enantiomer of indoline by a self-redox mechanism. The oxidative kinetic resolution of 2-aryl-substituted indolines proceeded to give enantiomers in good yields with excellent enantioselectivities. PMID- 26822189 TI - Did limits on payments for tobacco placements in US movies affect how movies are made? AB - OBJECTIVE: To compare how smoking was depicted in Hollywood movies before and after an intervention limiting paid product placement for cigarette brands. DESIGN: Correlational analysis. SETTING/PARTICIPANTS: Top box office hits released in the USA primarily between 1988 and 2011 (n=2134). INTERVENTION: The Master Settlement Agreement (MSA), implemented in 1998. MAIN OUTCOME MEASURES: This study analyses trends for whether or not movies depicted smoking, and among movies with smoking, counts for character smoking scenes and average smoking scene duration. RESULTS: There was no detectable trend for any measure prior to the MSA. In 1999, 79% of movies contained smoking, and movies with smoking contained 8 scenes of character smoking, with the average duration of a character smoking scene being 81 s. After the MSA, there were significant negative post-MSA changes (p<0.05) for linear trends in proportion of movies with any smoking (which declined to 41% by 2011) and, in movies with smoking, counts of character smoking scenes (which declined to 4 by 2011). Between 1999 and 2000, there was an immediate and dramatic drop in average length of a character smoking scene, which decreased to 19 s, and remained there for the duration of the study. The probability that the drop of -62.5 (95% CI -55.1 to -70.0) seconds was due to chance was p<10-16. CONCLUSIONS: This study's correlational data suggest that restricting payments for tobacco product placement coincided with profound changes in the duration of smoking depictions in movies. PMID- 26822190 TI - Transradial Coronary Angiography--Insights to the One-Catheter Concept. AB - Transradial coronary angiography (TRC) can be performed applying only one catheter fitting into the right and left coronary ostia (R/LCO). In this bicentric study (n = 2953), we analyzed the ostial performance of the Tiger_II_catheter widely used in TRC. Compared to Judkins catheters, the Tiger_II is frequently associated with ostial instability within the LCO but fits better into the RCO-irrespective of tube size. Judkins catheters generally need more peri-procedural contrast and radiation exposure. TRC may be started using a 5F_Tiger_II on the right side in order to be switched to 5F Judkins in case of propable LCO instability. PMID- 26822191 TI - [Risk assessment in percutaneous coronary intervention and appropriate use criteria: Manual or automatic? ]. PMID- 26822193 TI - Reductive Cyclopropanations Catalyzed by Dinuclear Nickel Complexes. AB - Dinuclear Ni complexes supported by naphthyridine-diimine (NDI) ligands catalyze the reductive cyclopropanation of alkenes with CH2 Cl2 as the methylene source. The use of mild terminal reductants (Zn or Et2 Zn) confers significant functional group tolerance, and the catalyst accommodates structurally and electronically diverse alkenes. Mononickel catalysts bearing related N chelates afford comparatively low cyclopropane yields (<=20 %). These results constitute an entry into catalytic carbene transformations from oxidized methylene precursors. PMID- 26822192 TI - Novel alleles of the VERNALIZATION1 genes in wheat are associated with modulation of DNA curvature and flexibility in the promoter region. AB - BACKGROUND: In wheat, the vernalization requirement is mainly controlled by the VRN genes. Different species of hexaploid and tetraploid wheat are widely used as genetic source for new mutant variants and alleles for fundamental investigations and practical breeding programs. In this study, VRN-A1 and VRN-B1 were analysed for 178 accessions representing six tetraploid wheat species (Triticum dicoccoides, T. dicoccum, T. turgidum, T. polonicum, T. carthlicum, T. durum) and five hexaploid species (T. compactum, T. sphaerococcum, T. spelta, T. macha, T. vavilovii). RESULTS: Novel allelic variants in the promoter region of VRN-A1 and VRN-B1 were identified based on the change in curvature and flexibility of the DNA molecules. The new variants of VRN-A1 (designated as Vrn-A1a.2, Vrn-A1b.2 - Vrn-A1b.6 and Vrn-A1i) were found to be widely distributed in hexaploid and tetraploid wheat, and in fact were predominant over the known VRN-A1 alleles. The greatest diversity of the new variants of VRN-B1 (designated as VRN-B1.f, VRN B1.s and VRN-B1.m) was found in the tetraploid and some hexaploid wheat species. For the first time, minor differences within the sequence motif known as the VRN box of VRN1 were correlated with wheat growth habit. Thus, vrn-A1b.3 and vrn A1b.4 were revealed in winter wheat in contrast to Vrn-A1b.2, Vrn-A1b.5, Vrn A1b.6 and Vrn-A1i. It was found that single nucleotide mutation in the VRN-box can influence the vernalization requirement and growth habit of wheat. Our data suggest that both the A-tract and C-rich segment within the VRN-box contribute to its functionality, and provide a new view of the hypothesised role of the VRN-box in regulating transcription of the VRN1 genes. Specifically, it is proposed that combination of mutations in this region can modulate vernalization sensitivity and flowering time of wheat. CONCLUSIONS: New allelic variants of the VRN-A1 and VRN-B1 genes were identified in hexaploid and tetraploid wheat. Mutations in A tract and C-rich segments within the VRN-box of VRN-A1 are associated with modulation of the vernalization requirement and flowering time. New allelic variants will be useful in fundamental investigations into the regulation of VRN1 expression, and provide a valuable genetic resource for practical breeding of wheat. PMID- 26822194 TI - Salivary duct carcinoma: a Danish national study. AB - BACKGROUND: To present the first national series of salivary duct carcinoma patients, including survival rates and an analysis of prognostic factors. METHODS: By merging three Danish nationwide registries that encompass an entire population, 34 patients diagnosed with salivary duct carcinoma from 1990 to 2005 were identified. Histological slides were reviewed, and data concerning demographics, tumour site, clinical stage, treatment profiles and follow-up were retrieved. Survival estimates and prognostic factors were evaluated by comparing Kaplan-Meier plots using the Mantel-Haenszel log-rank test. RESULTS: Salivary duct carcinoma showed an incidence of 0.04/100.000 inhabitants/year. Distant recurrence was seen in 52% of patients. Five-year overall survival, disease specific survival and recurrence-free survival were 32%, 42% and 35%, respectively. Univariate analyses suggested that overall stage (III/IV) and vascular invasion have a negative impact on all survival measures. Involved resection margins correlated with a poorer overall survival and disease-specific survival, whereas adjuvant radiotherapy improved overall survival and recurrence free survival. CONCLUSIONS: Salivary duct carcinoma incidence averages to two episodes per year in the entire Kingdom of Denmark. With half of patients in this study experiencing distant recurrences and only a third surviving at 5 years, prognosis is dismal. Advanced overall stage, vascular invasion and involved resection margins all seem to correlate with a poorer survival, while adjuvant radiotherapy significantly improved outcome. Extensive T-site surgery, neck dissection and adjuvant radiotherapy are therefore recommended. PMID- 26822195 TI - Origins of multicellular complexity: Volvox and the volvocine algae. AB - The collection of evolutionary transformations known as the 'major transitions' or 'transitions in individuality' resulted in changes in the units of evolution and in the hierarchical structure of cellular life. Volvox and related algae have become an important model system for the major transition from unicellular to multicellular life, which touches on several fundamental questions in evolutionary biology. The Third International Volvox Conference was held at the University of Cambridge in August 2015 to discuss recent advances in the biology and evolution of this group of algae. Here, I highlight the benefits of integrating phylogenetic comparative methods and experimental evolution with detailed studies of developmental genetics in a model system with substantial genetic and genomic resources. I summarize recent research on Volvox and its relatives and comment on its implications for the genomic changes underlying major evolutionary transitions, evolution and development of complex traits, evolution of sex and sexes, evolution of cellular differentiation and the biophysics of motility. Finally, I outline challenges and suggest future directions for research into the biology and evolution of the volvocine algae. PMID- 26822196 TI - Association between C-reactive protein and physical performance in older populations: results from the International Mobility in Aging Study (IMIAS). AB - BACKGROUND AND OBJECTIVE: C-reactive protein (CRP) is a widely used cardiovascular risk marker, but questions remain about its role in the disability process in old age. This study examines the associations between CRP levels and physical performance in old age in different societies. METHODS: data were collected during the baseline survey of IMIAS in 2012 in Kingston (Canada), Saint Hyacinthe (Canada), Manizales (Colombia) and Natal (Brazil). Approximately 200 men and 200 women aged 65-74 were recruited at each site. CRP was assessed using a high sensitivity assay and categorised as low (<1 mg/l), moderate (1-3 mg/l), high (3-10 mg/l) and very high (>=10 mg/l). Participants were interviewed at home; blood pressure, weight and height were measured. Physical function was assessed with the Short Physical Performance Battery (SPPB) and hand grip strength. Data were analysed using descriptive statistics, bivariate analysis (chi2) and linear or logistic regression. RESULTS: CRP was significantly associated with low hand grip strength and poor physical performance in bivariate analyses. Hand grip strength association with CRP disappeared after adjustment by socioeconomic factors and health behaviours. The odds of poor physical function was OR = 2.67 [95% CI 1.43-4.99] comparing the highest and lowest CRP categories after adjustment by relevant covariates. The three SPPB components were assessed separately. Graded associations between low CRP and faster gait speed and shorter time to rise from a chair were observed in adjusted models. Association between impaired balance and CRP was attenuated after adjustment by relevant covariates, OR = 1.15 [0.65-2.04]. CONCLUSIONS: CRP could be a possible pathway from inflammation to physical decline in older populations. PMID- 26822198 TI - Rheumatoid arthritis, TNF inhibitors, and non-melanoma skin cancer. PMID- 26822197 TI - Frequent variations in cancer-related genes may play prognostic role in treatment of patients with chronic myeloid leukemia. AB - BACKGROUND: Genome variability of host genome and cancer cells play critical role in diversity of response to existing therapies and overall success in treating oncological diseases. In chronic myeloid leukemia targeted therapy with tyrosine kinase inhibitors demonstrates high efficacy in most of the patients. However about 15 % of patients demonstrate primary resistance to standard therapy. Whole exome sequencing is a good tool for unbiased search of genetic variations important for prognosis of survival and therapy efficacy in many cancers. We apply this approach to CML patients with optimal response and failure of tyrosine kinase therapy. RESULTS: We analyzed exome variations between optimal responders and failures and found 7 variants in cancer-related genes with different genotypes in two groups of patients. Five of them were found in optimal responders: rs11579366, rs1990236, rs176037, rs10653661, rs3803264 and two in failures: rs3099950, rs9471966. These variants were found in genes associated with cancers (ANKRD35, DNAH9, MAGEC1, TOX3) or participating in cancer-related signaling pathways (THSD1, MORN2, PTCRA). CONCLUSION: We found gene variants which may become early predictors of the therapy outcome and allow development of new early prognostic tests for estimation of therapy efficacy in CML patients. Normal genetic variation may influence therapy efficacy during targeted treatment of cancers. PMID- 26822199 TI - Carboxylated and intact osteocalcin predict adiponectin concentration in hemodialyzed patients. AB - Purpose Disrupted bone metabolism in patients with chronic kidney disease (CKD) is associated with elevated concentrations of biochemical bone markers. Recently, animal studies show the role of osteocalcin in energy metabolism, which is partially confirmed in humans. The aim of our study was to evaluate the relationships between serum concentrations of bone markers and indices of energy metabolism in CKD patients on maintenance hemodialysis; in particular, the relationship between various forms of osteocalcin and adiponectin. Patients and methods The cross-sectional study included 155 hemodialyzed stage 5 CKD patients. Serum concentrations of glucose, insulin, adiponectin, bone alkaline phosphatase (bALP), tartrate resistant acid phosphatase (TRAP), carboxylated (cOC), undercarboxylated (ucOC), and intact osteocalcin (OC) were determined. Results In total cohort, bALP, TRAP, cOC, and ucOC negatively correlated with BMI. All analyzed bone markers positively correlated with adiponectin in total cohort and in men. In multiple linear regression analysis including all patients, log(cOC) and log(intact OC) were the only bone markers that predicted log(adiponectin) (beta = 0.22; p = 0.016 and beta = 0.26; p = 0.010) independently of sex, dialysis vintage, CRP, insulin, iPTH concentrations, BMI, and age. Conclusions Our data confirm the positive association between cOC, intact OC, and adiponectin concentrations in CKD patients on maintenance hemodialysis. PMID- 26822201 TI - Wet-Chemically Synthesized Colloidal Semiconductor Nanostructures as Optical Gain Media. AB - An overview on the development of wet-chemically synthesized semiconductor nanostructures as optical gain materials is presented in this Review, beginning with the first demonstration of amplified spontaneous emission in zero dimensional quantum dots and evolving to more sophisticated heterostructures such as one-dimensional core-seeded nanorods, branched core-seeded tetrapods and two dimensional nanoplatelets. The advantages and challenges of utilizing strongly quantum-confined colloidal semiconductor materials as gain media are discussed, and a concerted effort is made to elaborate on how the progression towards more structurally complex architectures has allowed for dramatic improvements in performance and stability over the archetypal quantum dot. PMID- 26822200 TI - In-depth analysis of cis-determinants that either promote or inhibit reinitiation on GCN4 mRNA after translation of its four short uORFs. AB - Translational control in eukaryotes is exerted by many means, one of which involves a ribosome translating multiple cistrons per mRNA as in bacteria. It is called reinitiation (REI) and occurs on mRNAs where the main ORF is preceded by a short upstream uORF(s). Some uORFs support efficient REI on downstream cistrons, whereas some others do not. The mRNA of yeast transcriptional activator GCN4 contains four uORFs of both types that together compose an intriguing regulatory mechanism of its expression responding to nutrients' availability and various stresses. Here we subjected all GCN4 uORFs to a comprehensive analysis to identify all REI-promoting and inhibiting cis-determinants that contribute either autonomously or in synergy to the overall efficiency of REI on GCN4. We found that the 3' sequences of uORFs 1-3 contain a conserved AU1-2A/UUAU2 motif that promotes REI in position-specific, autonomous fashion such as the REI-promoting elements occurring in 5' sequences of uORF1 and uORF2. We also identified autonomous and transferable REI-inhibiting elements in the 3' sequences of uORF2 and uORF3, immediately following their AU-rich motif. Furthermore, we analyzed contributions of coding triplets and terminating stop codon tetranucleotides of GCN4 uORFs showing a negative correlation between the efficiency of reinitiation and efficiency of translation termination. Together we provide a complex overview of all cis-determinants of REI with their effects set in the context of the overall GCN4 translational control. PMID- 26822203 TI - One-step sol-gel imprint lithography for guided-mode resonance structures. AB - Guided-mode resonance (GMR) structures consisting of sub-wavelength periodic gratings are capable of producing narrow-linewidth optical resonances. This paper describes a sol-gel-based imprint lithography method for the fabrication of submicron 1D and 2D GMR structures. This method utilizes a patterned polydimethylsiloxane (PDMS) mold to fabricate the grating coupler and waveguide for a GMR device using a sol-gel thin film in a single step. An organic-inorganic hybrid sol-gel film was selected as the imprint material because of its relatively high refractive index. The optical responses of several sol-gel GMR devices were characterized, and the experimental results were in good agreement with the results of electromagnetic simulations. The influence of processing parameters was investigated in order to determine how finely the spectral response and resonant wavelength of the GMR devices could be tuned. As an example potential application, refractometric sensing experiments were performed using a 1D sol-gel device. The results demonstrated a refractive index sensitivity of 50 nm/refractive index unit. This one-step fabrication process offers a simple, rapid, and low-cost means of fabricating GMR structures. We anticipate that this method can be valuable in the development of various GMR-based devices as it can readily enable the fabrication of complex shapes and allow the doping of optically active materials into sol-gel thin film. PMID- 26822202 TI - Deep brain stimulation-associated brain tissue imprints: a new in vivo approach to biological research in human Parkinson's disease. AB - BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) has been established as a highly effective symptomatic therapy for Parkinson's disease (PD). An intriguing biological aspect related to the DBS procedure is that a temporary contact establishes between surgical instruments and the surrounding brain tissue. In this exploratory study, we took advantage of this unique context to harvest brain material adhering to the stylet routinely used during surgery, and to examine the biological value of these samples, here referred to as "brain tissue imprints" (BTIs). RESULTS: Nineteen BTIs from 12 STN- or GPi-electrode implanted patients were obtained in vivo during DBS surgery, without any modification of the surgical procedure. Immunofluorescence analyses confirmed that our approach allowed the harvesting of many neural cells including neurons harboring distinct neurotransmitter markers. Shotgun proteomic and transcriptomic analyses provided for the first time molecular information from DBS-associated brain samples, and confirmed the compatibility of this new type of sample with poly-omic approaches. The method appears to be safe and results consistent. CONCLUSIONS: We here propose BTIs as original and highly valuable brain samples, and DBS-related brain imprinting as a new conceptual approach to biological research in living patients with PD. PMID- 26822204 TI - Integrin antagonists as potential therapeutic options for the treatment of Crohn's disease. AB - INTRODUCTION: Anti-integrin therapy for the treatment of patients with Crohn's disease is rapidly evolving. Two agents, natalizumab and vedolizumab, are approved by the United States Food and Drug Administration for the treatment of Crohn's disease, with vedolizumab the primary anti-integrin used due to a more favorable safety profile. Several other anti-integrins are in various stages of development. AREAS COVERED: This review discusses the current state of anti integrin therapy as well as suggestions for positioning of these agents in clinical practice. Emerging anti-integrin therapies, their underlying mechanisms of action, and available safety and clinical data are also reviewed. EXPERT OPINION: Anti-integrins are effective for the treatment of Crohn's disease, even in patients refractory to other therapies. Their use should be considered in patients with Crohn's disease who do not respond to, develop non-response to, or have contraindications to anti-TNF therapy. Anti-integrin therapies can be offered as a first biologic therapy, in particular for older patients, patients with concurrent multiple sclerosis (natalizumab only), and in patients with contraindications to anti-TNF therapy. In patients with more severe symptoms, providers should consider co-induction with corticosteroids if possible to hasten remission. PMID- 26822205 TI - Nucleophilic arylation with tetraarylphosphonium salts. AB - Organic phosphonium salts have served as important intermediates in synthetic chemistry. But the use of a substituent on the positive phosphorus as a nucleophile to construct C-C bond remains a significant challenge. Here we report an efficient transition-metal-free protocol for the direct nucleophilic arylation of carbonyls and imines with tetraarylphosphonium salts in the presence of caesium carbonate. The aryl nucleophile generated from phosphonium salt shows low basicity and good nucleophilicity, as evidenced by the successful conversion of enolizable aldehydes and ketones. The reaction is not particularly sensitive to water, shows wide substrate scope, and is compatible with a variety of functional groups including cyano and ester groups. Compared with the arylmetallic reagents that are usually moisture sensitive, the phosphonium salts are shelf-stable and can be easily handled. PMID- 26822206 TI - Medical Toxicology and the Crisis of Addiction--Introduction to the Proceedings from the 2015 ACMT Addiction Academy. PMID- 26822207 TI - Synthesis, Evaluation of Pharmacological Activity, and Molecular Docking of 1,4 Dihydropyridines as Calcium Antagonists. AB - 1,4-Dihydropyridine (DHP) is an important class of calcium antagonist. It inhibits the influx of extracellular Ca(2+) through L-type voltage-dependent calcium channels. Two series of nifedipine analogues were synthesized and evaluated as calcium antagonists. The ortho-nitrophenyl ring of nifedipine was replaced with an ortho- or a meta-chlorophenyl substituent. The IC50 values revealed that some of the compounds are similar to or more active than nifedipine. Substitution with groups of suitable bulkiness, such as ethyl ester, at the 3- and 5-positions of the DHP ring gave 3h, which is approximately three fold more active than nifedipine as a calcium antagonist. A docking study with the DHP receptor model was performed to interpret the differences in calcium antagonist activities. The molecular docking study demonstrated that the lipophilicity of the substituted phenyl group at the 4-position of the DHP ring is an important factor that could increase the activity of the calcium antagonist taking the steric factor into consideration. Bulky groups interfere with ring-to ring hydrophobic interaction with Tyr(1460) and limit the efficiency of increasing the length of the hydrocarbon chain of esters at the 3- and 5 positions of the DHP ring as an approach to increase activity. The presence of a chelating substituent on the phenyl ring at the 4-position of the DHP ring may ensure strong binding to the receptor and hence stabilization of the closed channel conformation. PMID- 26822208 TI - Constructal approach to cell membranes transport: Amending the 'Norton-Simon' hypothesis for cancer treatment. AB - To investigate biosystems, we propose a new thermodynamic concept that analyses ion, mass and energy flows across the cell membrane. This paradigm-shifting approach has a wide applicability to medically relevant topics including advancing cancer treatment. To support this claim, we revisit 'Norton-Simon' and evolving it from an already important anti-cancer hypothesis to a thermodynamic theorem in medicine. We confirm that an increase in proliferation and a reduction in apoptosis trigger a maximum of ATP consumption by the tumor cell. Moreover, we find that positive, membrane-crossing ions lead to a decrease in the energy used by the tumor, supporting the notion of their growth inhibitory effect while negative ions apparently increase the cancer's consumption of energy hence reflecting a growth promoting impact. Our results not only represent a thermodynamic proof of the original Norton-Simon hypothesis but, more concretely, they also advance the clinically intriguing and experimentally testable, diagnostic hypothesis that observing an increase in negative ions inside a cell in vitro, and inside a diseased tissue in vivo, may indicate growth or recurrence of a tumor. We conclude with providing theoretical evidence that applying electromagnetic field therapy early on in the treatment cycle may maximize its anti-cancer efficacy. PMID- 26822209 TI - The Healthy Heart-Mind trial: melatonin for prevention of delirium following cardiac surgery: study protocol for a randomized controlled trial. AB - BACKGROUND: Delirium is a common occurrence in patients undergoing major cardiac surgery and is associated with a number of adverse consequences for the individual, their family and the health system. Current approaches to the prevention of delirium include identifying those at risk together with various non-pharmacological and pharmacological strategies, although the efficacy of these is often modest. Emerging evidence suggests that melatonin may be biologically implicated in the development of delirium and that melatonin supplementation may be beneficial in reducing the incidence of delirium in medical and surgical patients. We designed this trial to determine whether melatonin reduces the incidence of delirium following cardiac surgery compared with placebo. METHODS/DESIGN: The Healthy Heart-Mind trial is a randomized, double-blind, placebo-controlled clinical trial of 3 mg melatonin or matching placebo administered on seven consecutive days for the prevention of delirium following cardiac surgery. We will recruit 210 adult participants, aged 50 and older, undergoing elective or semi-elective cardiac surgery with the primary outcome of interest for this study being the difference in the incidence of delirium between the groups within 7 days of surgery. Secondary outcomes of interest include the difference between groups in the severity and duration of delirious episodes, hospital length of stay and referrals to mental health services during admission. In addition, we will assess differences in depressive and anxiety symptoms, as well as cognitive performance, at discharge and 3 months after surgery. DISCUSSION: The results of this trial will clarify whether melatonin reduces the incidence of delirium following cardiac surgery. TRIAL REGISTRATION: The trial is registered with the Australian Clinical Trials Registry, trial number ACTRN12615000819527 (10 August 2015). PMID- 26822210 TI - ASDB: a resource for probing protein functions with small molecules. AB - : Identifying chemical probes or seeking scaffolds for a specific biological target is important for protein function studies. Therefore, we create the Annotated Scaffold Database (ASDB), a computer-readable and systematic target annotated scaffold database, to serve such needs. The scaffolds in ASDB were derived from public databases including ChEMBL, DrugBank and TCMSP, with a scaffold-based classification approach. Each scaffold was assigned with an InChIKey as its unique identifier, energy-minimized 3D conformations, and other calculated properties. A scaffold is also associated with drugs, natural products, drug targets and medical indications. The database can be retrieved through text or structure query tools. ASDB collects 333 601 scaffolds, which are associated with 4368 targets. The scaffolds consist of 3032 scaffolds derived from drugs and 5163 scaffolds derived from natural products. For given scaffolds, scaffold-target networks can be generated from the database to demonstrate the relations of scaffolds and targets. AVAILABILITY AND IMPLEMENTATION: ASDB is freely available at http://www.rcdd.org.cn/asdb/with the major web browsers. CONTACT: junxu@biochemomes.com or xujun9@mail.sysu.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26822211 TI - Proposal of Sphaerimonospora cavernae gen. nov., sp. nov. and transfer of Microbispora mesophila (Zhang et al., 1998) to Sphaerimonospora mesophila comb. nov. and Microbispora thailandensis (Duangmal et al., 2012) to Sphaerimonospora thailandensis comb. nov. AB - The actinomycete strain N74T, isolated from cave soil, was studied using a polyphasic taxonomic approach. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain N74T formed a stable, distinct lineage cluster together with Microbispora thailandensis NN276T (99.3% similarity) and Microbispora mesophila JCM 3151T (97.5%). Strain N74T was observed to produce single spherical spores on aerial mycelium as reported for M. mesophila JCM 3151T and M. thailandensis NN276T but different from other known species of the genus Microbispora, which are characterized by pairs of spores on aerial hyphae. Multilocus sequence analyses based on concatenated partial gyrB, rpoB, atpD, recA and 16S rRNA gene sequences showed a clear distinction of strain N74T, M. mesophila JCM 3151T and M. thailandensis NN276T from other members of the genus Microbispora, although the chemotaxonomic characteristics of strain N74T were similar to the genus Microbispora; the cell wall contained meso-diaminopimelic acid and the whole-cell hydrolysate contained madurose as the diagnostic sugar. The major menaquinone was MK-9(H4). The fatty acid profile contained iso-C16:0. On the basis of morphological, chemotaxonomic and phylogenetic evidence, strain N74T is assigned to a novel species of a new genus, for which the name Sphaerimonospora cavernae gen. nov., sp. nov. is proposed. The type strain of Sphaerimonospora cavernae is N74T (=BCC 77604T=NBRC 111481T). It is also proposed that M. mesophila and M. thailandensis be transferred to this genus as Sphaerimonospora mesophila comb. nov. (type strain JCM 3151T=NBRC 14179T=DSM 43048T) and Sphaerimonospora thailandensis comb. nov. (type strain NN276T=BCC 41490T=NBRC 107569T), respectively. PMID- 26822212 TI - Heavy metals in the surface sediments of the northern portion of the South China Sea shelf: distribution, contamination, and sources. AB - The concentrations of seven heavy metals (Cr, Ni, Cu, Zn, As, Cd, and Pb) in the surface sediments of the northern portion of the South China Sea (SCS) shelf collected between 2012 and 2014 were measured to assess the potential contamination levels and determine the environmental risks that are associated with heavy metals in the area. The measured concentrations in the sediments were 12.4-72.5 mg kg(-1) for Cr, 4.4-29.2 mg kg(-1) for Ni, 7.1-38.1 mg kg(-1) for Cu, 19.3-92.5 mg kg(-1) for Zn, 1.3-12.1 mg kg(-1) for As, 0.03-0.24 mg kg(-1) for Cd, and 8.5-24.4 mg kg(-1) for Pb. These results indicate that the heavy metal concentrations in the sediments generally meet the China Marine Sediment Quality criteria and suggest that the overall sediment quality of the northern portion of the SCS shelf has not been significantly impacted by heavy metal pollution. However, the enrichment factor (EF) and geoaccumulation index (I geo) clearly show that elevated concentrations of Cd occur in the region. A Pearson's correlation analysis was performed, and the results suggest that Cr, Ni, Cu, and Zn have a natural origin; Cd is primarily sourced from anthropogenic activities, with partial lithogenic components, and As and Pb may be affected by factors such as varying input sources or pathways (i.e., coal burning activities and aerosol precipitation). Heavy metal contamination mostly occurred to the east of Hainan Island, mainly because of the rapid economic and social developments in the Hainan Island. The results of this study will be useful for marine environment managers for the remediation of pollution sources. PMID- 26822213 TI - Effect of sludge characteristics on membrane fouling during start-up of a tertiary submerged membrane bioreactor. AB - In membrane bioreactors applied to wastewater treatment, fouling is typically a complex function of sludge characteristics. A pilot-scale tertiary submerged membrane bioreactor (tMBR) was continuously operated for over 200 days to assess the effect of biomass physiological state and environmental stress on process performance. Sludge characteristics were evaluated in terms of suspended solid concentration (MLSS and MLVSS), apparent viscosity, bioflocculation state, filterability, bioactivity, biopolymeric clusters (BPCs) and soluble microbial products. During the initial period of the tMBR start-up, when MLSS was below 3000 mg/L, the biomass was found to be very sensitive to environmental stress by sudden oxygen increase or organic shock loading, resulting in temporary biomass deflocculation and BPC release, and consequently, severe induced membrane fouling. However, at higher MLSS values, low stable biomass growth (0.04 +/- 0.002 kg MLVSS/kg COD) was measured, regardless of organic overloading shocks or feeding failures. This period was also characterised by low bioactivity, BPC content and membrane fouling. Statistical analysis showed that BPCs have an important role when compared with other sludge properties as indicators of its fouling potential. PMID- 26822215 TI - Structural benefits of bisphenol S and its analogs resulting in their high sorption on carbon nanotubes and graphite. AB - Bisphenol S (BPS), a new bisphenol analog, is considered to be a potential replacement for bisphenol A (BPA), which has gained concern because of its potentially adverse health impacts. Therefore, studies are needed to investigate the environmental fate and risks of this compound. In this study, the adsorption of BPS and four structural analogs on multi-walled carbon nanotubes (MWCNTs) and graphite (GP) were investigated. When solid-phase concentrations were normalized by the surface areas, oxygen-containing functional groups on the absorbents showed a positive impact on phenol sorption but inhibited the sorption of chemicals with two benzene rings. Among BPS analogs, diphenyl sulfone showed the lowest sorption when hydrophobic effects were ruled out. Chemicals with a butterfly structure, formed between the two benzene rings, showed consistently high sorption on MWCNTs, independent of the substituted electron-donating or accepting functional groups. This study emphasizes the importance of chemical conformation on organic, contaminant sorption on engineered, carbonaceous materials. PMID- 26822214 TI - Distribution, risk assessment, and statistical source identification of heavy metals in aqueous system from three adjacent regions of the Yellow River. AB - Distribution of five heavy metals (Cr, Pb, Cd, Cu, and Zn) and some physicochemical variables were studied from ten sites (S1-S10) in filtered water, suspended particles, and sediment samples from Gansu Province, Ningxia, and Inner Mongolia Autonomous Regions of the Yellow River in Northern China. The results showed that heavy metal concentrations in filtered water were relatively lower, while they were higher and approximated in suspended particles and sediment samples. Metal chemical fractions showed that high proportions of Cd were found in the exchangeable fractions, while others likely to be existed in lithology. Heavy metal pollution index (HPI) indicated that the quality of filtered water was relatively better, and the potential ecological risk index (PERI) revealed that only Cd has the higher ecological risk in suspended particles and sediment samples, which is accordance with the results obtained by the chemical fractions analysis; at the same time, the higher ecological risks existed in S3, S6, S9, and S10 in suspended particles and sediment samples due to the waste emission of a variety of industries. Results of cluster analysis (CA) indicated that contamination sources in the sediment samples were from both natural processes and anthropogenic activities. PMID- 26822216 TI - Distribution, enrichment, and potential toxicity of trace metals in the surface sediments of Sundarban mangrove ecosystem, Bangladesh: a baseline study before Sundarban oil spill of December, 2014. AB - The distribution, enrichment, and ecotoxicity potential of Bangladesh part of Sundarban mangrove was investigated for eight trace metals (As, Cd, Cr, Cu, Fe, Mn, Pb, and Zn) using sediment quality assessment indices. The average concentration of trace metals in the sediments exceeded the crustal abundance suggesting sources other than natural in origin. Additionally, the trace metals profile may be a reflection of socio-economic development in the vicinity of Sundarban which further attributes trace metals abundance to the anthropogenic inputs. A total of eleven surficial sediment samples were collected along a vertical transect along the freshwater-saline water gradient. The sediment samples were digested using EPA 3051 method and were analyzed on ICP-MS. Geo accumulation index suggests moderately polluted sediment quality with respect to Ni and As and background concentrations for Al, Fe, Mn, Cu, Zn, Pb, Co, As, and Cd. Contamination factor analysis suggested low contamination by Zn, Cr, Co, and Cd, moderate by Fe, Mn, Cu, and Pb while Ni and As show considerable and high contamination, respectively. Enrichment factors for Ni, Pb, and As suggests high contamination from either biota or anthropogenic inputs besides natural enrichment. As per the three sediment quality guidelines, Fe, Mn, Cu, Ni, Co, and As would be more of a concern with respect to ecotoxicological risk in the Sundarban mangroves. The correlation between various physiochemical variables and trace metals suggested significant role of fine grained particles (clay) in trace metal distribution whereas owing to low organic carbon content in the region the organic complexation may not be playing significant role in trace metal distribution in the Sundarban mangroves. PMID- 26822217 TI - Distribution and mobility of heavy elements in floodplain agricultural soils along the Ibar River (Southern Serbia and Northern Kosovo). Chemometric investigation of pollutant sources and ecological risk assessment. AB - This work investigates the influence of a high-magnitude flood event on heavy elements (HEs) pollution and mobility in the agricultural soils along Ibar River in Southern Serbia and Northern Kosovo. The study area was one of the most important Pb/Zn industrial regions in Europe. Soil samples (n = 50) collected before and after the floods in May 2014 were subjected to the sequential extraction procedure proposed by the Community Bureau of Reference (BCR). The results indicated that the floods significantly increased not only the pseudo total concentrations of HEs in the soil but also their mobile and potentially bioavailable amounts. Moreover, higher concentrations (both pseudo total and potentially bioavailable) were found in the agricultural soils closer to the industrial hotspots. Principal component analysis and hierarchical cluster analysis successfully grouped the analyzed elements according to their anthropogenic or natural origin. The floods significantly increased the potential ecological risk of HEs associated with Pb/Zn industrial activities in the study area. The potential ecological risk of Cd after the floods was highest and should be of special concern. PMID- 26822218 TI - Nitrogen removal performance in planted and unplanted horizontal subsurface flow constructed wetlands treating different influent COD/N ratios. AB - Microcosm horizontal subsurface flow constructed wetlands (HSSFCWs) were used to examine the impacts of vegetation on nitrogen dynamics treating different influent COD/N ratios (1:1, 4:1, and 8:1). An increase in the COD/N ratio led to increased reductions in NO3 and total inorganic nitrogen (TIN) in planted and unplanted wetlands, but diminished removal of NH4. The HSSFCW planted with Canna indica L. exhibited a significant reduction in NH4 compared to the unplanted system, particularly in the active root zone where NH4 removal performance increased by up to 26 % at the COD/N ratio of 8:1. There was no significant difference in NO3 removal between the planted and unplanted wetlands. TIN removal efficiency in the planted wetland increased with COD/N ratios, which was likely influenced by plant uptake. NH4 reductions were greater in planted wetland at the 20- and 40-cm depths while NO3 reductions were uniformly greater with depth in all cases, but no statistical difference was impacted by depth on TIN removal. These findings show that planting a HSSFCW can provide some benefit in reducing nitrogen loads in effluents, but only when a sufficient carbon source is present. PMID- 26822219 TI - Fluoride in weathered rock aquifers of southern India: Managed Aquifer Recharge for mitigation. AB - Climatic condition, geology, and geochemical processes in an area play a major role on groundwater quality. Impact of these on the fluoride content of groundwater was studied in three regions-part of Nalgonda district in Telangana, Pambar River basin, and Vaniyar River basin in Tamil Nadu, southern India, which experience semi-arid climate and are predominantly made of Precambrian rocks. High concentration of fluoride in groundwater above 4 mg/l was recorded. Human exposure dose for fluoride through groundwater was higher in Nalgonda than the other areas. With evaporation and rainfall being one of the major contributors for high fluoride apart from the weathering of fluoride rich minerals from rocks, the effect of increase in groundwater level on fluoride concentration was studied. This study reveals that groundwater in shallow environment of all three regions shows dilution effect due to rainfall recharge. Suitable managed aquifer recharge (MAR) methods can be adopted to dilute the fluoride rich groundwater in such regions which is explained with two case studies. However, in deep groundwater, increase in fluoride concentration with increase in groundwater level due to leaching of fluoride rich salts from the unsaturated zone was observed. Occurrence of fluoride above 1.5 mg/l was more in areas with deeper groundwater environment. Hence, practicing MAR in these regions will increase the fluoride content in groundwater and so physical or chemical treatment has to be adopted. This study brought out the fact that MAR cannot be practiced in all regions for dilution of ions in groundwater and that it is essential to analyze the fluctuation in groundwater level and the fluoride content before suggesting it as a suitable solution. Also, this study emphasizes that long-term monitoring of these factors is an important criterion for choosing the recharge areas. PMID- 26822220 TI - Individual and population-level responses to ocean acidification. AB - Ocean acidification is predicted to have detrimental effects on many marine organisms and ecological processes. Despite growing evidence for direct impacts on specific species, few studies have simultaneously considered the effects of ocean acidification on individuals (e.g. consequences for energy budgets and resource partitioning) and population level demographic processes. Here we show that ocean acidification increases energetic demands on gastropods resulting in altered energy allocation, i.e. reduced shell size but increased body mass. When scaled up to the population level, long-term exposure to ocean acidification altered population demography, with evidence of a reduction in the proportion of females in the population and genetic signatures of increased variance in reproductive success among individuals. Such increased variance enhances levels of short-term genetic drift which is predicted to inhibit adaptation. Our study indicates that even against a background of high gene flow, ocean acidification is driving individual- and population-level changes that will impact eco evolutionary trajectories. PMID- 26822222 TI - Congenital thrombotic thrombocytopenic purpura related to a novel mutation in ADAMTS13 gene and management during pregnancy. PMID- 26822221 TI - Peripheral neuropathy is a common manifestation of mitochondrial diseases: a single-centre experience. AB - BACKGROUND AND PURPOSE: Peripheral neuropathy in mitochondrial diseases (MDs) may vary from a subclinical finding in a multisystem syndrome to a severe, even isolated, manifestation in some patients. METHODS: To investigate the involvement of the peripheral nervous system in MDs extensive electrophysiological studies were performed in 109 patients with morphological, biochemical and genetic diagnosis of MD [12 A3243G progressive external ophthalmoplegia (PEO)/mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), 16 myoclonic epilepsy with ragged-red fibres (MERRF), four mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), 67 PEO with single or multiple deletions of mitochondrial DNA, 10 others]. RESULTS: A neuropathy was found in 49 patients (45%). The incidence was very high in MNGIE (100%), MELAS (92%) and MERRF (69%), whilst 28% of PEO patients had evidence of peripheral involvement. The most frequent abnormality was a sensory axonal neuropathy found in 32/49 patients (65%). A sensory-motor axonal neuropathy was instead detected in 16% of the patients and sensory-motor axonal demyelinating neuropathy in 16%. Finally one Leigh patient had a motor axonal neuropathy. It is interesting to note that the great majority had preserved tendon reflexes and no sensory disturbances. CONCLUSIONS: In conclusion, peripheral involvement in MD is frequent even if often mild or asymptomatic. The correct identification and characterization of peripheral neuropathy through electrophysiological studies represents another tile in the challenge of MD diagnosis. PMID- 26822223 TI - Elevation of serum squamous cell carcinoma antigen 2 in patients with psoriasis: associations with disease severity and response to the treatment. AB - BACKGROUND: Squamous cell carcinoma antigen (SCCA) belongs to the ovalbumin serpin family and is a known tumour marker. Expression of SCCA is upregulated in the serum and skin of patients with psoriasis. OBJECTIVES: The aim of this study was to determine SCCA2 levels in association with disease severity and treatment efficacy in patients with psoriasis. MATERIALS AND METHODS: Patients with psoriasis (n = 123) and healthy controls (n = 25) were enrolled in this prospective cross-sectional study. Enzyme-linked immunosorbent assay (ELISA) analysis was performed to determine serum SCCA2 levels. SCCA2 expression in skin was evaluated using immunohistochemical analysis. Serum SCCA2 levels were compared with Psoriasis Area Severity Index (PASI) scores. The effect of treatment on serum SCCA2 levels was assessed using serial examinations. Induction of SCCA2 by several psoriatic cytokines in human keratinocytes was evaluated. RESULTS: The serum levels of SCCA2 were significantly higher in patients with psoriasis than healthy controls and correlated well with disease severity. Increased SCCA2 staining was observed in lesional skin but not in nonlesional skin of patients with psoriasis. In addition, SCCA2 expression levels in skin correlated with serum concentrations of SCCA2. SCCA2 significantly decreased according to improvement of PASI scores. Interleukin (IL)-17 and IL-22 synergistically increased the production of SCCA2 at both mRNA and protein levels in human keratinocytes. CONCLUSIONS: Significant elevation of SCCA2 is associated with disease severity and reflects treatment efficacy. SCCA2 may be a useful biomarker in psoriasis, reflecting T-helper 17-type inflammation - the main determinant of the severity of psoriasis. PMID- 26822224 TI - Flow structures and red blood cell dynamics in arteriole of dilated or constricted cross section. AB - Vessel with 'circular' or 'star-shaped' cross sections are studied, representing respectively dilated or constricted cases where endothelial cells smoothly line or bulge into the lumen. Computational haemodynamics simulations are carried out on idealised periodic arteriole-sized vessels, with red blood cell 'tube' hematocrit value=24%. A further simulation of a single red blood cell serves for comparison purposes. The bulk motion of the red blood cells reproduces well-known effects, including the presence of a cell-free layer and the apparent shear thinning non-Newtonian rheology. The velocity flow field is analysed in a Lagrangian reference frame, relative to any given red blood cell, hence removing the bulk coaxial motion and highlighting instead the complex secondary flow patterns. An aggregate formation becomes apparent, continuously rearranging and dynamic, brought about by the inter-cellular fluid mechanics interactions and the deformability properties of the cells. The secondary flow field induces a vacillating radial migration of the red blood cells. At different radial locations, the red blood cells express different residence times, orientation and shape. The shear stresses exerted by the flow on the vessel wall are influenced by the motion of red blood cells, despite the presence of the cell-free layer. Spatial (and temporal) variations of wall shear stress patters are observed, especially for the 'circular' vessel. The 'star-shaped' vessel bears considerable stress at the protruding endothelial cell crests, where the stress vectors are coaxially aligned. The bulging endothelial cells hence regularise the transmission of stresses on the vessel wall. PMID- 26822225 TI - The role of cancer-associated fibroblasts in esophageal cancer. AB - Fibroblasts are known as critical stromal cells in wound healing by synthesizing extracellular matrix and collagen. A subpopulation of them is called cancer associated fibroblasts (CAFs), because their production of proteins participated in various biological activities including tumor cell proliferation, invasion and metastasis. Currently some studies shed light on their role in esophageal cancer which was an aggressive cancer with a dismal survival and high rate of metastasis. Thus, to find cures for it relies on elucidating the epithelial fibroblasts crosstalk. Herein, we reviewed the present knowledge of the CAFs' role in esophageal premalignant condition, cancer initiation, progression, metastasis and prognosis prediction and further provided some insights into its clinical application. PMID- 26822226 TI - One-dimensional Growth of Zinc Crystals on a Liquid Surface. AB - The catalyst-free growth of nanocrystals on various substrates at room temperature has been a long-standing goal in the development of material science. We report the growth of one-dimensional zinc nanocrystals on silicone oil surfaces by thermal evaporation method at room temperature (20 +/- 2 degrees C). Uniform zinc nanorods with tunable size can be obtained. The typical length and width of the nanorods are 250-500 nm and 20-40 nm, respectively. The growth mechanism can be attributed to the effect of the liquid substrate and the preferential growth direction of the crystals. This result provides a novel and simple way to fabricate the precursors (zinc crystals) for preparation of Zn based semiconductors and other metallic crystals on liquid substrates. PMID- 26822228 TI - THSD1 preserves vascular integrity and protects against intraplaque haemorrhaging in ApoE-/- mice. AB - AIMS: Impairment of the endothelial barrier leads to microvascular breakdown in cardiovascular disease and is involved in intraplaque haemorrhaging and the progression of advanced atherosclerotic lesions that are vulnerable to rupture. The exact mechanism that regulates vascular integrity requires further definition. Using a microarray screen for angiogenesis-associated genes during murine embryogenesis, we identified thrombospondin type I domain 1 (THSD1) as a new putative angiopotent factor with unknown biological function. We sought to characterize the role of THSD1 in endothelial cells during vascular development and cardiovascular disease. METHODS AND RESULTS: Functional knockdown of Thsd1 in zebrafish embryos and in a murine retina vascularization model induced severe haemorrhaging without affecting neovascular growth. In human carotid endarterectomy specimens, THSD1 expression by endothelial cells was detected in advanced atherosclerotic lesions with intraplaque haemorrhaging, but was absent in stable lesions, implying involvement of THSD1 in neovascular bleeding. In vitro, stimulation with pro-atherogenic factors (3% O2 and TNFalpha) decreased THSD1 expression in human endothelial cells, whereas stimulation with an anti atherogenic factor (IL10) showed opposite effect. Therapeutic evaluation in a murine advanced atherosclerosis model showed that Thsd1 overexpression decreased plaque vulnerability by attenuating intraplaque vascular leakage, subsequently reducing macrophage accumulation and necrotic core size. Mechanistic studies in human endothelial cells demonstrated that THSD1 activates FAK-PI3K, leading to Rac1-mediated actin cytoskeleton regulation of adherens junctions and focal adhesion assembly. CONCLUSION: THSD1 is a new regulator of endothelial barrier function during vascular development and protects intraplaque microvessels against haemorrhaging in advanced atherosclerotic lesions. PMID- 26822227 TI - Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue engineering. AB - Recent advances in regenerative medicine place us in a unique position to improve the quality of engineered tissue. We use auricular cartilage as an exemplar to illustrate how the use of tissue-specific adult stem cells, assembly through additive manufacturing and improved understanding of postnatal tissue maturation will allow us to more accurately replicate native tissue anisotropy. This review highlights the limitations of autologous auricular reconstruction, including donor site morbidity, technical considerations and long-term complications. Current tissue-engineered auricular constructs implanted into immune-competent animal models have been observed to undergo inflammation, fibrosis, foreign body reaction, calcification and degradation. Combining biomimetic regenerative medicine strategies will allow us to improve tissue-engineered auricular cartilage with respect to biochemical composition and functionality, as well as microstructural organization and overall shape. Creating functional and durable tissue has the potential to shift the paradigm in reconstructive surgery by obviating the need for donor sites. PMID- 26822229 TI - Surgical outcomes of hepatocellular carcinoma with biliary tumor thrombus: a systematic review. AB - BACKGROUND: Hepatocellular carcinoma (HCC) with biliary tumor thrombus (BTT) is rare and its impact on postoperative prognosis remains controversial. The aim of this study was to evaluate the published evidence concerning the outcome of surgical resection of HCC with BTT. METHODS: Eligible studies were identified by searching PubMed and reviewed systematically. Comparisons of the clinicopathologic features and surgical outcomes for HCC patients with or without BTT were analyzed using meta-analytical techniques. RESULTS: Twenty retrospective studies containing 598 patients that met the selection criteria were included for review. The perioperative mortality was 2.1 % (range, 0-10 %), and the median 5 year overall survival (OS) was 24 % (range, 0-48 %) with a recurrence rate of 63.9 % (range, 42-91 %). Pooled analysis of 13 comparative studies showed that HCC patients with BTT had a higher incidence of vascular invasion (odds ratio [OR]: 4.70, 95 % CI: 2.90-7.60; P <0.001), a higher frequency of poor differentiation (OR: 2.07, 95 % CI: 1.23-3.49; P = 0.006), and a shorter 5-year OS rate (OR: 0.31, 95 % CI: 0.21-0.64; P <0.001) than those without BTT. CONCLUSIONS: Although HCC with BTT has more aggressive biological characteristics and is an indicator of poor prognosis, surgical resection can still provide long term survival for some patients. PMID- 26822230 TI - A longitudinal study of risk and protective factors associated with successful transition to secondary school in youth with ADHD: prospective cohort study protocol. AB - BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) has a significant impact on child and adolescent development, especially in relation to school functioning and academic outcomes. Despite the transition to high school being a potentially critical period for children with ADHD, most research in this period has focused on academic outcomes. This study aims to extend previous research by describing academic, school engagement, behaviour and social-emotional outcomes for young people with ADHD in the first and third years of high school and to identify risk and protective factors predictive of differing outcomes across these four domains. METHODS AND DESIGN: The Moving Up study is a longitudinal, prospective cohort study of children with ADHD as they transition and adjust to high school (age 12-15 years). Data are collected through direct assessment and child, parent and teacher surveys. The primary outcome is academic achievement, obtained by linking to standardised test results. Secondary outcomes include measures of behaviour, ADHD symptoms, school engagement (attitudes and attendance), and social and emotional functioning, including depressive symptoms. The mean performance of the study cohort on each outcome measure will be compared to the population mean for same aged children, using t-tests. Risk and protective factors to be examined using multiple regression include a child, family and school factors know to impact academic and school functioning. DISCUSSION: The Moving up study is the first Australian study prospectively designed to measure a broad range of student outcomes for children with ADHD during the high school transition period. Examining both current (cross sectional) and earlier childhood (longitudinal) factors gives us the potential to learn more about risk and protective factors associated with school functioning in young people with ADHD. The richness and depth of this information could lead to more targeted and effective interventions that may alter academic and wellbeing trajectories for young people at risk of poor outcomes. The study is approved by The Royal Children's Hospital Melbourne Human Research Ethics Committee (33206). Findings will be disseminated through peer-reviewed journals and conference presentations. PMID- 26822231 TI - Technetium Tc 99m sulfur colloid phenotypic probe for the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin in women with ovarian cancer. AB - PURPOSE: Significant variability in the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin (PLD) exists. PLD undergoes clearance via the mononuclear phagocyte system (MPS). Technetium Tc 99m sulfur colloid (TSC) is approved for imaging MPS cells. We investigated TSC as a phenotypic probe of PLD pharmacokinetics and pharmacodynamics in women with epithelial ovarian cancer. METHODS: TSC 10 mCi IVP was administered and followed by dynamic planar and SPECT/CT imaging and blood pharmacokinetics sampling. PLD 30-40 mg/m(2) IV was administered with or without carboplatin, followed by plasma pharmacokinetics sampling. RESULTS: There was a linear relationship between TSC clearance and encapsulated doxorubicin clearance (R(2) = 0.61, p = 0.02), particularly in patients receiving PLD alone (R(2) = 0.81, p = 0.04). There was a positive relationship (rho = 0.81, p = 0.01) between maximum grade palmar-plantar erythrodysesthesia toxicity developed and estimated encapsulated doxorubicin concentration in hands. CONCLUSIONS: TSC is a phenotypic probe for PLD pharmacokinetics and pharmacodynamics and may be used to individualize PLD therapy in ovarian cancer and for other nanoparticles in development. PMID- 26822234 TI - Lewis-acid-promoted catalytic cascade conversion of glycerol to lactic acid by polyoxometalates. AB - The polyoxometalates AlPMo12O40 and CrPMo12O40 show high activity and reusablility for cascade conversion of glycerol directly to lactic acid under mild conditions without the addition of base, and can be reused more than 12 times with 90.5% selectivity at 93.7% conversion. AlPMo12O40 is tolerant to crude glycerol from biodiesel production. PMID- 26822232 TI - Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes. AB - A genome-wide exome association study has identified the transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 variant encoding an E167K substitution as a genetic determinant of hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). The roles of this variant across a spectrum of liver diseases and pathologies and on serum lipids comparing viral hepatitis to NAFLD and viral load in chronic viral hepatitis, as well as its intrahepatic molecular signature, have not been well characterized. We undertook detailed analyses in 3260 subjects with viral and nonviral liver diseases and in healthy controls. Serum inflammatory markers and hepatic expression of TM6SF2 and genes regulating lipid metabolism were assessed in a subset with chronic hepatitis C (CHC). The rs58542926 T allele was more prevalent in 502 NAFLD patients than controls (P = 0.02) but not different in cohorts with CHC (n = 2023) and chronic hepatitis B (n = 507). The T allele was associated with alterations in serum lipids and hepatic steatosis in all diseases and with reduced hepatic TM6SF2 and microsomal triglyceride transfer protein expression. Interestingly, the substitution was associated with reduced CHC viral load but increased hepatitis B virus DNA. The rs58542926 T allele had no effect on inflammation, impacted >=F2 fibrosis in CHC and NAFLD assessed cross sectionally (odds ratio = 1.39, 95% confidence interval 1.04-1.87, and odds ratio = 1.62, 95% confidence interval 1.03-2.52, respectively; P < 0.03 for both), but had no effect on fibrosis progression in 1174 patients with CHC and a known duration of infection. CONCLUSION: The TM6SF2 E167K substitution promotes steatosis and lipid abnormalities in part by altering TM6SF2 and microsomal triglyceride transfer protein expression and differentially impacts CHC and chronic hepatitis B viral load, while effects on fibrosis are marginal. (Hepatology 2016;64:34-46). PMID- 26822233 TI - Osmotically-induced tension and the binding of N-BAR protein to lipid vesicles. AB - The binding affinity of a curvature-sensing protein domain (N-BAR) is measured as a function of applied osmotic stress while the membrane curvature is nearly constant. Varying the osmotic stress allows us to control membrane tension, which provides a probe of the mechanism of binding. We study the N-BAR domain of the Drosophila amphiphysin and monitor its binding on 50 nm-radius vesicles composed of 90 mol% DOPC and 10 mol% PIP. We find that the bound fraction of N-BAR is enhanced by a factor of approximately 6.5 when the tension increases from zero to 2.6 mN m(-1). This tension-induced response can be explained by the hydrophobic insertion mechanism. From the data we extract a hydrophobic domain area that is consistent with known structure. These results indicate that membrane stress and strain could play a major role in the previously reported curvature-affinity of N BAR. PMID- 26822235 TI - The importance of endothelium-derived mediators to the efficacy of dual anti platelet therapy. PMID- 26822236 TI - Social influences on use of cigarettes, e-cigarettes, and hookah by college students. AB - OBJECTIVES: (1) Compare social norms and perceived peer use between college student cigarette, e-cigarette, and/or hookah users and nonusers; and (2) determine variables associated with social influences. PARTICIPANTS: Undergraduate students attending a large university in the Southeast United States (N = 511). METHODS: An April 2013 online survey assessed use of 3 types of tobacco, social norms, perception of peer use, number of smokers in life, exposure to secondhand smoke, and demographic characteristics. RESULTS: Participants indicated greater acceptance of emerging tobacco products than for cigarettes and consistently overestimated the percent of peers who use various tobacco products. Males and current users had higher social norm scores for all 3 forms of tobacco. CONCLUSION: To counter marketing of alternative tobacco products, education about the dangers of their use needs to be implemented across college campuses as part of a comprehensive tobacco control strategy that also includes tobacco-free campus policies. PMID- 26822237 TI - Diagnostic Yield of Clinical Tumor and Germline Whole-Exome Sequencing for Children With Solid Tumors. AB - Importance: Whole-exome sequencing (WES) has the potential to reveal tumor and germline mutations of clinical relevance, but the diagnostic yield for pediatric patients with solid tumors is unknown. Objective: To characterize the diagnostic yield of combined tumor and germline WES for children with solid tumors. Design: Unselected children with newly diagnosed and previously untreated central nervous system (CNS) and non-CNS solid tumors were prospectively enrolled in the BASIC3 study at a large academic children's hospital during a 23-month period from August 2012 through June 2014. Blood and tumor samples underwent WES in a certified clinical laboratory with genetic results categorized on the basis of perceived clinical relevance and entered in the electronic health record. Main Outcomes and Measures: Clinical categorization of somatic mutations; frequencies of deleterious germline mutations related to patient phenotype and incidental medically-actionable mutations. Results: Of the first 150 participants (80 boys and 70 girls, mean age, 7.4 years), tumor samples adequate for WES were available from 121 patients (81%). Somatic mutations of established clinical utility (category I) were reported in 4 (3%) of 121 patients, with mutations of potential utility (category II) detected in an additional 29 (24%) of 121 patients. CTNNB1 was the gene most frequently mutated, with recurrent mutations in KIT, TSC2, and MAPK pathway genes (BRAF, KRAS, and NRAS) also identified. Mutations in consensus cancer genes (category III) were found in an additional 24 (20%) of 121 tumors. Fewer than half of somatic mutations identified were in genes known to be recurrently mutated in the tumor type tested. Diagnostic germline findings related to patient phenotype were discovered in 15 (10%) of 150 cases: 13 pathogenic or likely pathogenic dominant mutations in adult and pediatric cancer susceptibility genes (including 2 each in TP53, VHL, and BRCA1), 1 recessive liver disorder with hepatocellular carcinoma (TJP2), and 1 renal diagnosis (CLCN5). Incidental findings were reported in 8 (5%) of 150 patients. Most patients harbored germline uncertain variants in cancer genes (98%), pharmacogenetic variants (89%), and recessive carrier mutations (85%). Conclusions and Relevance: Tumor and germline WES revealed mutations in a broad spectrum of genes previously implicated in both adult and pediatric cancers. Combined reporting of tumor and germline WES identified diagnostic and/or potentially actionable findings in nearly 40% of newly diagnosed pediatric patients with solid tumors. PMID- 26822238 TI - Axially diethylaminophenoxypropanoxy substituted new subphthalocyanines: synthesis and electropolymerization properties. AB - The treatment of boron(III) subphthalocyanine chloride with 1,3-bis[3 (diethylamino)phenoxy]propan-2-ol 2 and 2,3-bis[3-(diethylamino)phenoxy]propan-1 ol 4 in toluene gave the corresponding axially substituted boron(III) subphthalocyanine compounds 3 and 5. The novel axially diethylaminophenoxypropanoxy substituted subphthalocyanines were characterized by standard spectroscopy methods. The electropolymerization properties of new axially diethylaminophenoxypropanoxy substituted subphthalocyanines were also characterized by using cyclic and square wave voltammetry techniques. This study is the first example of electropolymerization of axially substituted subphthalocyanines in the literature. PMID- 26822239 TI - Intrinsic and Extrinsic Charge Transport in CH3NH3PbI3 Perovskites Predicted from First-Principles. AB - Both intrinsic and extrinsic charge transport properties of methylammonium lead triiodide perovskites are investigated from first-principles. The weak electron phonon couplings are revealed, with the largest deformation potential (~ 5 eV) comparable to that of single layer graphene. The intrinsic mobility limited by the acoustic phonon scattering is as high as a few thousands cm(2) V(-1) s(-1) with the hole mobility larger than the electron mobility. At the impurity density of 10(18) cm(-3), the charged impurity scattering starts to dominate and lowers the electron mobility to 101 cm(2) V(-1) s(-1) and the hole mobility to 72.2 cm(2) V(-1) s(-1). The high intrinsic mobility warrants the long and balanced diffusion length of charge carriers. With the control of impurities or defects as well as charge traps in these perovskites, enhanced efficiencies of solar cells with simplified device structures are promised. PMID- 26822240 TI - The interaction between social saliency and perceptual saliency. AB - The ability to select visual targets in hierarchical stimuli can be affected by both perceptual saliency and social saliency. However, the functional relations between the effects are not understood. Here we examined whether these two factors interact or combine in an additive way. Participants first learnt to associate geometric shapes with three people (e.g., triangle-self, square stranger). After learning the associations, participants were presented with compound stimuli (e.g., a global triangle formed by a set of local squares) and had to select a target at the global or local level. In Experiment 1 the task was to identify the person associated with the local or global shape. In Experiment 2 the task was simply to identify the shape. We manipulated perceptual saliency by blurring local elements to form perceptually global salient stimuli or by contrasting the colours of neighbouring local elements (red vs. white) to form perceptually local salient stimuli. In Experiment 1 (person discrimination) there was a strong effect of saliency on local targets (there were faster and more accurate responses to high than to low saliency targets) when social and perceptual saliency occurred at same level. However, both perceptual and social saliency effects were eliminated when the effect of saliency at one level competed with that at the other level. In Experiment 2 (shape discrimination), there were only effects of perceptual saliency. The data indicate that social saliency interacts with perceptual saliency when explicit social categorizations are made, consistent with both factors modulating a common process of visual selection. PMID- 26822241 TI - [Ethics, medical ethics, and occupational medicine: is their dialogue possible?]. AB - Today's medicine faces some critical moral challenges, yet the medical class suffers from an increasingly evident malaise: a growing dissatisfaction with an ethical demand often perceived as a cumbersome burden of rules and prohibitions, which risk to erode the fiduciary relations with patients. Such a negative appraisal is partly due to a narrow interpretation of the meaning of ethics, a misconception whose roots are in the positivistic stance that permeates our culture, and in its almost exclusively technological bent. This radical orientation of our culture shows itself in the vanishing of the idea of an intrinsic ethical dimension of medicine and consequent eclipse of traditional medical ethics, currently all but assimilated by bioethics. Maintaining a clear distinction between medical ethics and bioethics is a fundamental condition for guaranteeing an original ethical reflection in medicine, thereby fostering a constructive dialogue between philosophical and medical ethics. In this sense, occupational medicine holds a very propitious position, at the cross-roads to some of the most important dimensions in human life and society: health, work, environment. In a milieu which is too often inclined to efface the living human being and the deepest needs of humanity, the moral commitment of medical profession to the care of the integral reality of the embodied human person is one of the most important ethical challenges facing occupational medicine and a most valuable contribution to the current ethical debate. PMID- 26822242 TI - [Early effects of PCE exposure on visual function among dry cleaning workers]. AB - BACKGROUND: A number of studies have shown a possible correlation between exposure to perchlorethylene (PCE) in dry cleaning workers and impairment of colour perception. OBJECTIVES: to ascertain the possible presence of alterations in visual function in a group of workers exposed to current limit value levels of PCE. METHODS: The study was conducted on 38 workers exposed to PCE in 21 dry cleaning establishments in the district of Modena and 60 controls selected according to criteria of comparability. We measured exposure to PCE among the dry cleaning workers using environmental monitoring (mean exposure 16.9 mg/m3). Both groups then answered a medical history questionnaire and underwent the Ishihara test for evaluating exclusion criteria followed by Lanthony D15d and Visual Acuity in Contrast Reduced (VCS) tests to evaluate changes in visual function. The results of Lanthony's test were expressed using Index Confusion Chromatic (ICC). RESULTS: In the cases the average value of ICC was 1.28 (DS 0.21) and in the controls 1.15 (SD 0.21); the difference was statistically significant (p <0.01). The values of ICC tended to be worse in subjects engaged only in the washing phase, who also had higher levels of exposure to PCE (mean exposure 26.8 mg/m3). The values of VCS for each frequency did not show, however, significant differences between the two groups. CONCLUSIONS: On this basis, our data indicate that occupational exposure to PCE well below the current limit values may still be able to induce impairment of colour perception and that such levels are therefore not adequately protective, at least against these effects. PMID- 26822243 TI - [Malignant mesotheliomas with unknown exposure to asbestos: a re-examination]. AB - INTRODUCTION: Malignant Mesothelioma (MM) is a rare neoplasm associated with asbestos exposure. In 24,5% of MM cases reported to the Lombardy Mesothelioma Registry (LMR), asbestos exposure has been defined as "unknown". OBJECTIVE: To evaluate the cases with "unknown exposure to asbestos" diagnosed in 2000-2004 in agreement with new knowledge about source of asbestos exposure. METHODS: Information regarding exposure has been reviewed in order to select the cases susceptible of further investigations, including: interview of relatives and/or colleagues; further evaluations by local PSAL (Prevention and Security in workplace) services; contact of industrial hygienists; analysis of production processes. The same procedure has been followed for extra-occupational exposure. These cases have been subjected to the LMR evaluation group. RESULTS: Fourthy four out of 364 (12,1%) MM have been reclassified. In 47,7% of the cases, a "possible occupational exposure" has been recognized, 15,9% have been attributed a "certain occupational exposure", while 36,4% an extra-occupational (domestic, environmental and leisure-time) exposure. No significant differences between age, sex, cancer site, diagnostic certainty, residence, year of diagnosis, interviewed subjects were detected. The occupational sector with the highest amount of reclassifications was the clothing production. CONCLUSIONS: The detailed reconstruction of clinical and occupational history and of lifestyle habits of patients affected by MM, close cooperation with Local Services of Occupational Medicine and literature review make it possible for previously overlooked asbestos exposure to be acknowledged. PMID- 26822244 TI - [Asbestos exposure assessment in the first case of intrasplenic mesothelioma]. AB - BACKGROUND: In 2013 the International Journal of Surgical Pathology published a case report of intrasplenic malignant mesothelioma (MM) in a 48-year-old man: it was the first report in literature describing a case of primitive intra-splenic MM, described without a history of asbestos exposure. OBJECTIVE: To verify the possible past exposure to asbestos, ignored by the patient himself, by studying in depth his environmental and occupational history. METHODS: Information about the occupational and non-occupational history of the subject was collected by Experts of the Operational Unit of Occupational Health and Safety Control (UOC PSAL) of the Local Health Unit Umbria 1 - Perugia, using the Italian National Mesothelioma Register (ReNaM) questionnaire and guide lines; an inspection was carried out at the past canning industry where the patient worked in the period 1982-1990 and material was taken to be analysed by MOCF and SEM. RESULTS: Samples showed the presence of asbestos fibres belonging to the amphibole class (amosite and crocidolite) and to the serpentine class (chrysotile). CONCLUSIONS: The survey described the past occupational exposure to asbestos in a canning industry, where the subject worked in the period 1982-1990, unknown to the patient himself. The authors strongly confirm the usefulness of standardized methods, such as the ReNaM Questionnaire, and the importance of technical expertise of the investigator to find and analyse the suspect materials and to demonstrate possible past occupational exposure to asbestos. PMID- 26822245 TI - Job satisfaction among radiology assistants: a multicentre cross-sectional study in Italy. AB - OBJECTIVES: Job satisfaction among physicians is an important occupational health issue since it is related to different factors such as work motivation or career decisions. The aim of this study was to investigate job satisfaction among radiology assistants for the first time in Italy. METHODS: In 2012, a cross sectional survey was conducted among a convenience sample of radiology assistants drawn from all Italian regions who submitted an electronic or paper-based self administered questionnaire. The data collected were analysed using logistic regressions in order to assess the role of socio-demographic variables. RESULTS: Overall, 574 radiology assistants were interviewed. More than half of the subjects were males and were younger than 40 years old. Around 76% of the sample was not satisfied as regards salary. Moreover, the majority of the participants (66.1%) was not satisfied with the professional refresher courses. Compared with males, females were more satisfied in terms of professional enrichment (OR=1.79, 95% CI: 1.23-2.62) but less satisfied with their relationships with superiors (OR=0.57, 95% CI: 0.38-0.85). CONCLUSIONS: Since radiology assistants and, in general, healthcare workers assist medical doctors, thus playing a significant role in safeguarding patients' health , it would be desirable to give due importance to the issue of job satisfaction, from all points of view. PMID- 26822246 TI - [Perception of shift work, burnout and sleep disturbances: a study among call centre operators]. AB - BACKGROUND: Shift work is often considered to be a factor that can negatively affect health and sleep quality. However, it is usually considered as a structural factor of the job and not as a perception of a work demand. OBJECTIVES: The study aimed at analyzing the relationship between perception of shift work, burnout and sleep disturbances in a potentially stressful context, namely the call centre setting. METHODS: Call centre operators (N=510) completed a questionnaire encompassing the following scales: perceptions of shift work, monotony, time pressure, exhaustion, cynicism and sleep disturbances. We conducted two hierarchical regressions in order to analyze the contribution of the perception of shift work on burnout dimensions (exhaustion and cynicism), beyond the contribution of socio-demographical variables, and of two specific job stressors for call centre operators, namely monotony and time pressure. The mediating role of exhaustion and cynicism between the perception of shift work and sleep disturbances was also explored. RESULTS: The perception of shift work was associated with operators' burnout, beyond the effect of socio-demographic variables and other job stressors. In addition, the relationship between the perception of shift work and sleep disturbances was fully mediated by exhaustion and partially mediated by cynicism. CONCLUSIONS: Perceived shift work may represent a risk factor for the health of call centre operators that should be monitored and possibly managed through specific organizational interventions. PMID- 26822247 TI - [Professional divers: analysis of critical issues and proposal of a health protocol for work fitness]. AB - INTRODUCTION: From many years now, thanks to the development of modern diving techniques, there has been a rapid spread of diving activities everywhere. In fact, divers are ever more numerous both among the Armed Forces and civilians who dive for work, like fishing, biological research and archeology. AIM: The aim of the study was to propose a health protocol for work fitness of professional divers keeping in mind the peculiar work activity, existing Italian legislation that is almost out of date and the technical and scientific evolution in this occupational field. METHOD: We performed an analysis of the most frequently occurring diseases among professional divers and of the clinical investigation and imaging techniques used for work fitness assessment of professional divers. RESULTS: From analysis of the health protocol recommended by D.M. 13 January 1979 (Ministerial Decree), that is most used by occupational health physician, several critical issues emerged. Very often the clinical investigation and imaging techniques still used are almost obsolete, ignoring the execution of simple and inexpensive investigations that are more useful for work fitness assessment. CONCLUSIONS: Considering the out-dated legislation concerning diving disciplines, it is necessary to draw up a common health protocol that takes into account clinical and scientific knowledge and skills acquired in this area. This protocol's aim is to propose a useful tool for occupational health physicians who work in this sector. PMID- 26822248 TI - Interstitial lung disease in a female worker sensitized to epoxy resins: a case report submitted for discussion. PMID- 26822249 TI - [Non-Hodgkin lymphoma and asbestos exposure]. PMID- 26822250 TI - The global health dimensions of asbestos and asbestos-related diseases. AB - The Collegium Ramazzini (CR) reaffirms its long-standing position that responsible public health action is to ban all extraction and use of asbestos, including chrysotile. This current statement updates earlier statements by the CR with a focus on global health dimensions of asbestos and asbestos-related diseases (ARDs). The ARD epidemic will likely not peak for at least a decade in most industrialized countries and for several decades in industrializing countries. Asbestos and ARDs will continue to present challenges in the arena of occupational medicine and public health as well as in clinical research and practice, and have thus emerged as a global health issue. Industrialized countries that have already gone through the transition to an asbestos ban have learned lessons and acquired know-how and capacity that could be of great value if deployed in industrializing countries embarking on the transition. The accumulated wealth of experience and technologies in industrialized countries should thus be shared internationally through global campaigns to eliminate ARDs. PMID- 26822253 TI - Multispecies Swarms of Social Microorganisms as Moving Ecosystems. AB - Microorganisms use collective migration to cross barriers and reach new habitats, and the ability to form motile swarms offers a competitive advantage. Traditionally, dispersal by microbial swarm propagation has been studied in monoculture. Microorganisms can facilitate other species' dispersal by forming multispecies swarms, with mutual benefits. One party (the transporter) moves a sessile partner (the cargo). This results in asymmetric associations ranging from temporary marriages of convenience to long-term fellow travellers. In the context of the 'microbial market', the parties offer very different services in exchange. We discuss bacteria transporting bacteria, eukaryotic microorganisms moving bacteria, and bacteria facilitating the spread of eukaryotes - and ask what the benefits are, the methods of study, and the consequences of multispecies, swarming logistics networks. PMID- 26822254 TI - Strategies for the Total Synthesis of Clavicipitic Acid. AB - Clavicipitic acid is an ergot alkaloid, which was isolated from Claviceps strain and Claviceps fusiformis. Its unique tricyclic azepinoindole skeleton has attracted synthetic chemists, and various strategies have been developed for its total synthesis. These strategies can be generally categorized into two types based on the synthetic intermediates, namely, 4-substituted gramine derivatives and 4-substituted tryptophan derivatives. This Minireview summarizes the reported total syntheses from the point of these two key intermediates. PMID- 26822255 TI - High-Precision Twist-Controlled Bilayer and Trilayer Graphene. AB - Twist-controlled bilayer graphene (tBLG) and double-twisted trilayer graphene (DTTG) with high precision are fabricated and their controllable optoelectronic properties are investigated for the first time. The successful fabrication of tBLG and DTTG with designated theta provides an attractive starting point for systematic studies of interlayer coupling in misoriented few-layer graphene systems with well-defined geometry. PMID- 26822256 TI - Correction to All Two-Dimensional, Flexible, Transparent, and Thinnest Thin Film Transistor. PMID- 26822257 TI - Mechanisms and origins of the switchable regioselectivity of FeBr3-catalyzed [1,2]-aryl and [1,2]-alkyl shifts of alpha-aryl aldehydes. AB - With the aid of DFT calculations, the FeBr3-catalyzed skeletal rearrangements of 2-cyclohexanal,2-p-C6H4OMe-propylaldehyde (1A) and 2-phenyl,2-p-C6H4OMe propylaldehyde (1B) were investigated theoretically. As compared to mono-FeBr3 as a catalyst, the bis-FeBr3 serving as a catalyst is found to be not only enhancing the catalytic efficiency but also improving the product selectivity. For the reaction starting from 1A, the [1,2]-group shift (first step) is rate determining, and why the Cy shift is the most favored is rationalized in comparison with the p-C6H4OMe and Me shifts. For the reaction starting from 1B, the [1,2]-H shift (second step) is rate-determining although the [1,2]-p-C6H4OMe shift is favored over the [1,2]-phenyl shift. In contrast to the experimental proposal, the newly established H2O/Br(-) joint-assisted H-shift mechanism explains the partial alpha-H source of the [1,2]-Cy shift product. In addition, we discussed the inherent mechanism that explains why both the [1,2]-p-C6H4OMe and [1,2]-p-C6H4CF3 shifts are more facile than the [1,2]-phenyl shift although the substituents -OMe and -CF3 have opposite electronic behaviors. PMID- 26822258 TI - Neuromyelitis optica spectrum disorder associated with osmotic demyelination syndrome. PMID- 26822259 TI - Enhancement of local bone remodeling in osteoporotic rabbits by biomimic multilayered structures on Ti6Al4V implants. AB - To enhance long-term survival of titanium implants in patients with osteoporosis, chitosan/gelatin multilayers containing bone morphogenetic protein 2(BMP2) and an antiosteoporotic agent of calcitonin (CT) are deposited on the Ti6Al4V (TC4) implants through layer-by-layer (LBL) electrostatic assembly technique. Here, the obtained titanium alloy implant (TC4/LBL/CT/BMP2) can regulate the release of loaded calcitonin and BMP2 agents in a sustaining manner to accelerate the bone formation and simultaneously inhibit bone resorption. In vitro results show that the bone-related cells on TC4/LBL/CT/BMP2 present the lowest production level of tartrate resistant acid phosphatase (TRAP) but the highest (p < 0.05) level of alkaline phosphatase (ALP) activity, osteocalcin production, mineralization capacity and osteoblast-related gene expression among all groups after treatment for 7 or 21 days, respectively. Besides, in vivo studies of micro-CT analysis, routine histological and immunohistochemical analysis also collectively demonstrate that the TC4/LBL/CT/BMP2 implant can dramatically promote the formation and remodeling of new bone in osteoporotic rabbits after implantation for 30 days and 90 days, respectively. In vivo push-out testing further confirms that the TC4/LBL/CT/BMP2 implant has the highest (p < 0.01) interfacial shear strength and favorable bone-implant osseointegration. Overall, this study establishes a simple and profound methodology to fabricate a biofunctional TC4 implant for the treatment of local osteoporotic fractures in vivo. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1437-1451, 2016. PMID- 26822261 TI - The effectiveness of regular leisure-time physical activities on long-term glycemic control in people with type 2 diabetes: A systematic review and meta analysis. AB - The objective of this study was to systematically review the effectiveness of different types of regular leisure-time physical activities and pooled the effect sizes of those activities on long-term glycemic control in people with type 2 diabetes compared with routine care. This review included randomized controlled trials from 1960 to May 2014. A total of 10 Chinese and English databases were searched, following selection and critical appraisal, 18 randomized controlled trials with 915 participants were included. The standardized mean difference was reported as the summary statistic for the overall effect size in a random effects model. The results indicated yoga was the most effective in lowering glycated haemoglobin A1c (HbA1c) levels. Meta-analysis also revealed that the decrease in HbA1c levels of the subjects who took part in regular leisure-time physical activities was 0.60% more than that of control group participants. A higher frequency of regular leisure-time physical activities was found to be more effective in reducing HbA1c levels. The results of this review provide evidence of the benefits associated with regular leisure-time physical activities compared with routine care for lowering HbA1c levels in people with type 2 diabetes. PMID- 26822260 TI - A high thyroid stimulating hormone level is associated with diabetic peripheral neuropathy in type 2 diabetes patients. AB - AIM: The association between thyroid stimulating hormone (TSH) and type 2 diabetes mellitus (T2DM) is well known. However, whether TSH is related to diabetic peripheral neuropathy (DPN) has not been studied. The aim of this study was to explore the relationship between TSH and DPN in Chinese patients with T2DM. METHODS: In this cross-sectional study, 605 patients with T2DM were enrolled. Subclinical hypothyroidism (SCH) was defined as an elevated TSH level (>4.0mIU/L) and a normal free thyroxine level. DPN was evaluated by neurological symptoms, neurological signs, and electromyogram. RESULTS: Serum TSH levels were significantly higher in DPN and signs of DPN compared with non-DPN T2DM patients (both P<0.01).The prevalence of DPN and signs of DPN in SCH subjects was higher than that in euthyroid subjects (both P<0.01). Spearman's correlation analysis showed that the serum TSH level was positively associated with DPN (r=0.172, P<0.01). A significant independent association between TSH and DPN was found by multiple logistic regression analysis after adjusting for potential confounding variables [odds ratio (OR)=1.365, P<0.01]. The patients were sequentially assigned to quartiles according to TSH level. Compared with quartile 1, patients in quartile 2 (P<0.01), quartile 3 (P=0.01), and quartile 4 (P<0.01) had a higher risk of DPN. Receiver-operating characteristic curve analysis revealed that the optimal cutoff point of TSH to indicate DPN was 3.045mIU/L in men and 2.94mIU/L in women. CONCLUSION: TSH level is independently associated with DPN in Chinese population with T2DM. A high serum TSH level may be a potential risk factor for DPN. PMID- 26822262 TI - Successful switch from insulin to oral sulfonylurea therapy in HNF1A-MODY Tunisian patient with the P291fsinsC mutation. AB - The hot spot mutation P291fsinsC was identified for the first time in a 26 years old Tunisian woman. The low serum level of high C-reactive protein was helpful to target the HNF1A gene. Due to the molecular diagnosis, the change from insulin to sulfonylurea therapy was performed successfully. PMID- 26822263 TI - Examining the Role of Sphingosine Kinase-2 in the Regulation of Endothelial Cell Barrier Integrity. AB - OBJECTIVE: A key mediator of vascular EC barrier integrity, S1P, is derived from phosphorylation of sphingosine by the SK-1 and SK-2. While previous work indicates that SK-1 can regulate EC barrier integrity, whether SK-2 has a similar role remains to be determined. METHODS: A cell impedance assay was used to assess human umbilical vein EC and bone marrow EC barrier integrity in vitro, with application of the SK inhibitors ABC294640, PF543, SKi, and MP-A08. In vivo studies were conducted using intravital microscopy to assess EC barrier integrity in SK-1 (Sphk1(-/-)) and SK-2 (Sphk2(-/-)) knock-out mice. RESULTS: Only ABC294640 and MP-A08, which can both inhibit SK-2, caused a decrease in EC barrier integrity in vitro in both cell types. Intravital microscopy revealed that Sphk1(-/-) mice had reduced EC barrier integrity compared to WT mice, whereas no change was evident in Sphk2(-/-) mice. CONCLUSIONS: Our data suggest that in vitro inhibition of SK-2, can compromise the integrity of the EC monolayer, while SK-1 exerts a more dominant control in vivo. These data may have clinical implications and could aid in the development of new treatments for disorders of vascular barrier function. PMID- 26822264 TI - Acid Sensitive Polymeric Micelles Combining Folate and Bioreducible Conjugate for Specific Intracellular siRNA Delivery. AB - An efficiently siRNA transporting nanocarrier still remains to be developed. In this study, utilizing the dual stimulus of acid tumor extracellular environment and redox effect of glutathione in the cytosol, a new siRNA transporting system combining triple effects of folate targeting, acid sensitive polymer micelles, and bio-reducible disulfide bond linked siRNA-cell penetrating peptides (CPPs) conjugate is developed to suppress c-myc gene expression of breast cancer (MCF-7 cells) both in vitro and in vivo. Subsequent research demonstrates that the vesicle has particle size of about 100 nm and siRNA entrapment efficiency of approximately 80%. In vitro studies verified over 90% of encapsulated siRNA-CPPs can be released and the vesicle shows higher cellular uptake in response to the tumorous zone. Determination of gene expression at both mRNA and protein levels indicates the constructed vesicle exhibited enhanced cancer cell apoptosis and improved therapeutic efficacy in vitro and in vivo. PMID- 26822265 TI - The Effect of Platelet-Rich-Plasma on the Healing of Left Colonic Anastomosis in a Rat Model of Intra-Abdominal Sepsis. AB - OBJECTIVE: The aim of this study was to investigate the effect of platelet-rich plasma (PRP) on the healing of colonic anastomosis in the presence of sepsis. MATERIALS AND METHOD: Fifty Wistar-albino male rats were used. Ten healthy rats were euthanized to prepare PRP, the rest were subjected to colonic anastomosis and randomly allocated into four groups of 10 rats each as anastomosis without PRP (C), without PRP in sepsis (SC), anastomosis with PRP (C-PRP), and with PRP in sepsis (S-PRP). Sepsis was induced by cecal ligation and puncture procedure. All animals were euthanized on postoperative day 7. The body weight change, anastomotic bursting pressure (ABP), tissue hydroxyproline (TH) and histopathological examination of each group were analyzed by using one-way analysis of variance (ANOWA) and Tukey's HSD post-hoc test to assess the differences between the groups. RESULTS: There was no statistical difference among the groups in terms of body weight changes. The ABP was measured at a mean value of 179.5 +/- 10.3, 129.3 +/- 14.2, 209 +/- 14.4, and 167.5 +/- 7.5 mm-Hg, in group C, SC, C-PRP, and S-PRP, respectively. The ABP and TH of C-PRP group was significantly higher than three groups (p < .05, for each comparison). In sepsis, PRP significantly raised the mean ABP and TH levels up to the levels of C group. Tissue regeneration was significant with increased collagen formation in C-PRP group than the other groups (p < .05). The healing effect of PRP in the presence of sepsis was significant than S-group (p < .05), while similar to C group (p = .181). CONCLUSION: PRP application to colonic anastomosis promotes the healing process in rats with intra-abdominal sepsis. PMID- 26822266 TI - Feasibility of Home-Based Functional Status Assessment of Chronic Obstructive Pulmonary Disease Patients Recovering From an Exacerbation. AB - INTRODUCTION: The Glittre Activities of Daily Living Test (ADL-Test) is a reliable functional status measurement for stable chronic obstructive pulmonary disease (COPD) patients in a laboratory setting. We aimed to adapt the test to the home setting (mADL-Test) and to follow-up the functional status recovery of post-exacerbation COPD patients included in a home hospitalization (HH) program. METHOD: We assessed 17 exacerbated moderate-to-very-severe COPD patients in 3 home visits: at discharge to HH (V0), 10days (V10post) and 1month after discharge (V30post). Patients completed the mADL-Test (laps, VO2 and VE), COPD assessment test (CAT), London Chest ADL Test (LCADL), modified Medical Research Council (mMRC) and upper limb strength (handgrip). RESULTS: The number of laps of the mADL-Test (4, 5 and 5, P<.05), CAT (19, 12 and 12, P<.01), mMRC (2, 1.5 and 1, P<.01) and the self-care domain of the LCADL (6, 5 and 5, P<.01) improved during follow-up (V0, V10post and V30post, respectively). No significant changes were evidenced in VO2, VE or handgrip. CONCLUSION: Our results suggest that the mADL test can be performed in the home setting after a COPD exacerbation, and that functional status continues to improve 10days after discharge to HH. PMID- 26822267 TI - Assessing Bystander Behavior Intentions Toward Friends to Prevent Dating Violence: Development of the Bystander Behavior Intentions-Friends Scale Through Concept Mapping and Exploratory Factor Analysis. AB - Bystander behavior interventions aim to reduce violence by encouraging individuals to intervene in a safe and effective manner when they hear or see circumstances that could lead to violence. This study used a participatory-based approach to develop a 9-item scale to measure bystander behaviors to prevent dating violence among friends. Predominantly, female students (N = 37) on a college campus in the Mid-Atlantic region of the United States were asked to define bystander behaviors. Responses were thematically sorted and ranked according to importance in preventing dating violence and feasibility by 12 participants. Psychometric testing of intentions to perform the behavior was done based on responses from an additional 288 respondents. Exploratory factor analysis was used to examine whether bystander behaviors directed at friends to prevent dating violence was a uni- or multidimensional construct, which has not been done to date in the available literature. Results demonstrated a unidimensional factor structure with strong factor loadings (above .71) and internal consistency (Cronbach's alpha .92); items focused on primary and secondary prevention behaviors toward friends. These findings provide a reliable and single construct scale to assess college-age women's response to witnessing the victimization of a friend. These findings can facilitate future program evaluations. PMID- 26822268 TI - The truth about trauma readmissions. AB - BACKGROUND: There is a paucity of data on the causes and associated patient factors for unplanned readmissions among trauma patients. METHODS: We examined patients admitted for traumatic injuries between 2007 and 2011 in the California State Inpatient Database. Using chi-square tests and multivariate logistic regression models, we determined rates, reasons, locations, and patient factors associated with 30-day readmissions. RESULTS: Among 252,752 trauma discharges, the overall readmission rate was 7.56%, with 36% of readmissions occurring at a hospital different from the hospital of initial admission. Predictors of readmissions included being discharged against medical advice (odds ratio [OR]: 2.56 [2.35 to 2.76]); Charlson scores >=2 (OR: 2.00 [1.91 to 2.10]); and age >=45 years (OR: 1.29 [1.25 to 1.33]). Major reasons for readmissions were musculoskeletal complaints (22.29%), psychiatric conditions (9.40%), and surgical infections (6.69%). CONCLUSIONS: Health and social vulnerabilities influence readmission among trauma patients, with many readmitted at other hospitals. Targeted interventions among high-risk patients may reduce readmissions after traumatic injuries. PMID- 26822269 TI - Management of suspected adrenal metastases at 2 academic medical centers. AB - BACKGROUND: The optimal management of suspected adrenal metastases remains controversial. METHODS: This is a retrospective bi-institutional review of 37 patients who underwent adrenalectomy for suspected adrenal metastasis between 2001 and 2014. RESULTS: Three (8%) patients had benign adenomas on final pathology. At a median follow-up of 21 months, 7 (32%) patients were alive with no evidence of disease and 7 (32%) were alive with recurrent disease. Recurrence free survival (RFS) was 8 months; decreased RFS was associated with positive margins and size >=6 cm. Overall survival (OS) was 29 months; decreased OS was associated with capsular disruption. There were no differences in RFS or OS by surgical approach. CONCLUSIONS: The favorable OS supports adrenalectomy in select patients with suspected adrenal metastases. Minimally invasive adrenalectomy is safe and effective, but the surgical approach should be based on the ability to achieve a margin-negative resection with avoidance of capsular disruption. PMID- 26822270 TI - Supporting SIDS Families: The Public Health Nurse SIDS Home Visit. AB - Sudden infant death syndrome (SIDS) death has a devastating effect on parents. There is no known cause, so parents experience guilt about what they might have done or not done to contribute to the death. Although some SIDS parents may receive support from family and friends, the public health nurse (PHN) has an important professional role in providing grief support, SIDS education, and offering SIDS resources and referrals. Based on years of clinical practice, we recommend the following: Perform the home visit as soon as possible. Show care and compassion. Personalize the baby by using his or her name and asking to see photographs. Reassure the parents that grief is a process which takes time. Educate about what SIDS is and what it is not. Increasingly, SIDS deaths occur in the presence of risk factors. Explain that risk factors are not causes of death. As an authority in health care, reassuring families that they did not cause their baby's death has a tremendous impact on relieving guilt. Putting newly bereaved SIDS parents in contact with other SIDS parents is one of the most helpful actions a PHN can take to help families. PMID- 26822271 TI - A Comparison of Methods to Test for Mediation in Multisite Experiments. AB - A Monte Carlo study extended the research of MacKinnon, Lockwood, Hoffman, West, and Sheets (2002) for single-level designs by examining the statistical performance of four methods to test for mediation in a multilevel experimental design. The design studied was a two-group experiment that was replicated across several sites, included a single intervening variable and outcome, and assumed that the effects of the treatment and mediator were constant across sites. The findings provide new evidence of the benefits of and further support for using the asymmetric confidence limits approach to test for mediation. In addition, the authors provide further support for using confidence intervals to assess if treatment effects are completely mediated, as using traditional hypothesis testing may lead to erroneous conclusions. PMID- 26822272 TI - Testing Linear Models for Ability Parameters in Item Response Models. AB - Methods for testing hypotheses concerning the regression parameters in linear models for the latent person parameters in item response models are presented. Three tests are outlined: A likelihood ratio test, a Lagrange multiplier test and a Wald test. The tests are derived in a marginal maximum likelihood framework. They are explicitly formulated for the 3-parameter logistic model, but it is shown that the approach applies to a broad class of item response models. Since the distributions of the test statistics are derived asymptotically, simulation studies were performed to assess the Type I error rates of the tests for small realistic sample sizes. Overall, the Type I error rates for the null hypothesis that a regression coefficient equals zero, were close to the nominal significance level. A number of power studies were conducted. It is argued that on theoretical grounds the power of the Lagrange multiplier test might be less than the power of the other two tests, but this expectation was not corroborated. The robustness of the tests to violation of the item response model was investigated with simulation studies of the power and Type I error rate. The results showed that the performance of the tests was acceptable in the cases where local independence and the constancy of the discrimination parameters over treatment groups were violated to the same extent for all treatment groups. The simulation studies also showed that the tests were biased if local independence was violated for one of the treatment groups. PMID- 26822273 TI - A Latent-Change Scaling Model for Longitudinal Multiple Choice Data. AB - A latent-change scaling model for the analysis of repeated-measures multiple choice data is presented. The model extends previous work by combining latent class analysis and low dimensional scaling techniques in a longitudinal framework where subjects may change their preferences for the response categories over time. The latent structural component of the model characterizes both the cross sectional heterogeneity of the population and an underlying change process over time; the measurement component of the model uses a scaling procedure to produce a joint representation of latent classes and response categories in a low dimensional space that represents individual differences in the utilities of the categories. An analysis of a national panel data set is used to illustrate both aspects of the model. A hypothetical example illustrates additional features of the model that can be tested when multiple indicators are collected at each time point. PMID- 26822274 TI - Relating Factor Models for Longitudinal Data to Quasi-Simplex and NARMA Models. AB - In this article we show the one-factor model can be rewritten as a quasi-simplex model. Using this result along with addition theorems from time series analysis, we describe a common general model, the nonstationary autoregressive moving average (NARMA) model, that includes as a special case, any latent variable model with continuous indicators and continuous latent variables. As an example, we show the NARMA representations of the linear growth curve model and the growth curve model with estimated basis vector coefficients. In certain instances rewriting competing models may help the investigator to compare different models. Here we compare the "hybrid" behavior genetics model of Eaves and Hewitt to the quasi-simplex model of Boomsma and Molenaar and show that both have equivalent NARMA representations which differ only in order. PMID- 26822275 TI - Fit Indices Versus Test Statistics. AB - Model evaluation is one of the most important aspects of structural equation modeling (SEM). Many model fit indices have been developed. It is not an exaggeration to say that nearly every publication using the SEM methodology has reported at least one fit index. Most fit indices are defined through test statistics. Studies and interpretation of fit indices commonly assume that the test statistics follow either a central chi-square distribution or a noncentral chi-square distribution. Because few statistics in practice follow a chi-square distribution, we study properties of the commonly used fit indices when dropping the chi-square distribution assumptions. The study identifies two sensible statistics for evaluating fit indices involving degrees of freedom. We also propose linearly approximating the distribution of a fit index/statistic by a known distribution or the distribution of the same fit index/statistic under a set of different conditions. The conditions include the sample size, the distribution of the data as well as the base-statistic. Results indicate that, for commonly used fit indices evaluated at sensible statistics, both the slope and the intercept in the linear relationship change substantially when conditions change. A fit index that changes the least might be due to an artificial factor. Thus, the value of a fit index is not just a measure of model fit but also of other uncontrollable factors. A discussion with conclusions is given on how to properly use fit indices. PMID- 26822276 TI - Recognition of MBR Reviewers. PMID- 26822277 TI - Experimental and Computational Analysis of the Solvent-Dependent O2/Li(+)-O2(-) Redox Couple: Standard Potentials, Coupling Strength, and Implications for Lithium-Oxygen Batteries. AB - Understanding and controlling the kinetics of O2 reduction in the presence of Li(+)-containing aprotic solvents, to either Li(+)-O2(-) by one-electron reduction or Li2 O2 by two-electron reduction, is instrumental to enhance the discharge voltage and capacity of aprotic Li-O2 batteries. Standard potentials of O2 /Li(+)-O2(-) and O2/O2(-) were experimentally measured and computed using a mixed cluster-continuum model of ion solvation. Increasing combined solvation of Li(+) and O2(-) was found to lower the coupling of Li(+)-O2(-) and the difference between O2/Li(+)-O2(-) and O2/O2(-) potentials. The solvation energy of Li(+) trended with donor number (DN), and varied greater than that of O2 (-) ions, which correlated with acceptor number (AN), explaining a previously reported correlation between Li(+)-O2(-) solubility and DN. These results highlight the importance of the interplay between ion-solvent and ion-ion interactions for manipulating the energetics of intermediate species produced in aprotic metal oxygen batteries. PMID- 26822278 TI - Donor-derived exosomes induce specific regulatory T cells to suppress immune inflammation in the allograft heart. AB - To inhibit the immune inflammation in the allografts can be beneficial to organ transplantation. This study aims to induce the donor antigen specific regulatory T cells (Treg cell) inhibit the immune inflammation in the allograft heart. In this study, peripheral exosomes were purified from the mouse serum. A heart transplantation mouse model was developed. The immune inflammation of the allograft heart was assessed by histology and flow cytometry. The results showed that the donor antigen-specific T helper (Th)2 pattern inflammation was observed in the allograft hearts; the inflammation was inhibited by immunizing the recipient mice with the donor-derived exosomes. Purified peripheral exosomes contained integrin MMP1a; the latter induced CD4(+) T cells to express Fork head protein-3 and transforming growth factor (TGF)-beta via inhibiting the Th2 transcription factor, GATA binding protein 3, in CD4(+) T cells. Administration with the donor-derived exosomes significantly prolonged the allograft heart survival. We conclude that the donor-derived peripheral exosomes have the capacity to inhibit the immune inflammation in the allograft heart via inducing specific Treg cells, implicating that administration with the donor-derived exosomes may be beneficial to cardiac transplantation. PMID- 26822281 TI - Scrutinizing the double superconducting gaps and strong coupling pairing in (Li(1 x)Fe(x))OHFeSe. AB - In the field of iron-based superconductors, one of the frontier studies is about the pairing mechanism. The recently discovered (Li(1-x)Fe(x))OHFeSe superconductor with the transition temperature of about 40 K provides a good platform to check the origin of double superconducting gaps and high transition temperature in the monolayer FeSe thin film. Here we report a scanning tunnelling spectroscopy study on the (Li(1-x)Fe(x))OHFeSe single crystals. The tunnelling spectrum mimics that of the monolayer FeSe thin film and shows double gaps at about 14.3 and 8.6 meV. Further analysis based on the quasiparticle interference allows us to rule out the d-wave gap, and for the first time assign the larger (smaller) gap to the outer (inner) Fermi pockets (after folding) associating with the dxy (dxz/dyz) orbitals, respectively. The gap ratio amounts to 8.7, which demonstrates the strong coupling mechanism in the present superconducting system. PMID- 26822280 TI - Prenatal and postnatal stress and wheeze in Mexican children: Sex-specific differences. AB - BACKGROUND: Increasing evidence links early-life exposure to psychosocial stress with adverse childhood respiratory outcomes. The influence of exposure timing has not been completely elucidated. OBJECTIVE: To examine the association between prenatal and postnatal maternal stress and wheeze in 417 children enrolled in a prospective birth cohort in Mexico City. METHODS: Maternal negative life event (NLE) scores were ascertained in the second or third trimester of pregnancy and at the 48-month postnatal visit. Children's respiratory outcomes, caregiver report of ever wheeze, and wheeze in the past 12 months were obtained from the International Study of Asthma and Allergies in Childhood survey administered at 48 months. Associations between prenatal and postnatal NLE scores and wheeze were analyzed using a modified Poisson regression approach adjusting for covariates. RESULTS: In separate models, higher maternal psychosocial stress during pregnancy (relative risk [RR], 1.12; 95% CI, 1.00-1.26) and postnatally (RR, 1.21; 95% CI, 1.08-1.35) were associated with increased risk of wheeze in the past 12 months with an evident exposure-response relationship. There was a significant interaction between postnatal stress and sex in relation to current wheeze. In a sex-stratified model, the association between postnatal stress and risk of wheeze in the past 12 months was stronger in girls (RR, 1.35; 95% CI, 1.13-1.61) than in boys (RR, 1.11; 95% CI, 0.97-1.27) (P for interaction = .04). CONCLUSION: Prenatal and postnatal stress in mothers was associated with wheeze in preschool aged children, and the effect of postnatal stress was stronger in girls. Understanding the temporal- and sex-specific effects of stress may better inform prevention strategies. PMID- 26822279 TI - Utility of low-dose oral aspirin challenges for diagnosis of aspirin-exacerbated respiratory disease. AB - BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is diagnosed through graded aspirin challenges that induce hypersensitivity reactions and eicosanoid level changes. It is not known whether diagnostically useful changes also occur after low-dose aspirin challenges that do not induce hypersensitivity reactions. OBJECTIVE: To investigate the utility of low-dose oral aspirin challenges for diagnosing AERD by measuring different clinical parameters and eicosanoid changes. METHODS: Sixteen patients with AERD and 13 patients with aspirin tolerant asthma underwent oral challenges with low-dose (20 or 40 mg) aspirin and diagnostic oral graded aspirin challenges (up to 325 mg of aspirin). Forced expiratory volume in 1 second, nasal peak flow, the fraction of exhaled nitric oxide (FeNO), and eicosanoid levels in plasma and urine were analyzed. RESULTS: In patients with AERD but not in those with aspirin-tolerant asthma, 40-mg aspirin challenges induced a significant mean (SEM) decrease from baseline in FeNO (19% [5.1%]; P = .001) without causing any hypersensitivity reaction. The FeNO decrease also occurred after higher-dose aspirin challenges (27.8% [4.9%]; P < .001). The sensitivity and specificity of 40-mg aspirin-induced FeNO changes for identifying AERD were 90% and 100% with an area under the curve of 0.98 (95% CI, 0.92-1.00). The low-dose challenge also induced a significant leukotriene E4 urine increase in patients with AERD (from 6.32 [0.08] to 6.91 [0.15] log-pg/mg creatinine; P < .001), but the sensitivity and specificity of these changes were less than for the FeNO changes. CONCLUSION: The low-dose aspirin-induced decrease in FeNO in patients with AERD may be useful for the diagnosis of aspirin allergy without inducing a hypersensitivity reaction. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01320072. PMID- 26822283 TI - Weak self-directed learning skills hamper performance in cumulative assessment. AB - BACKGROUND: Self-regulated learning is an important determinant of academic performance. Previous research has shown that cumulative assessment encourages students to work harder and improve their results. However, not all students seem to respond as intended. We investigated the influence of students' behavioral traits on their responsiveness to a cumulative assessment strategy. METHOD: The cumulative test results of a third-year integrated ten-week course unit were analyzed. The test was divided into three parts delivered at 4, 8 and 10 weeks. Low starters (below median) with low or high improvement (below or above the median) were identified and compared regarding their behavioral traits (assessed with the Temperament and Character Inventory questionnaire). RESULTS: A total of 295 students filled out the questionnaire. A percentage of 70% of the students below the median on the first two test parts improved during the final part. Students who were less responsive to improve their test results, scored low only on the TCI scale "self directedness" (t = 2.49; p = 0.011). CONCLUSION: Behavioral traits appear to influence student reactions to feedback on test results, with students with low self-directedness scores being particularly at risk. They can thus be identified and should receive special attention from student counselors. PMID- 26822282 TI - Aortic Root Distortion and Aortic Insufficiency During Balloon Angioplasty of the Right Ventricular Outflow Tract Prior to Transcatheter Pulmonary Valve Replacement. AB - OBJECTIVE: To describe the significance of aortic root distortion (AD) and/or aortic valve insufficiency (AI) during balloon angioplasty of the right ventricular outflow tract (RVOT) performed to rule out coronary artery compression prior to transcatheter pulmonary valve (TPV) implantation. METHODS: AD/AI was assessed by retrospective review of all procedural aortographies performed to evaluate coronary anatomy prior to TPV implantation. AD/AI was also reviewed in all pre-post MPV implant echocardiograms to assess for progression. RESULTS: From 04/2007 to 3/2015, 118 pts underwent catheterization with intent for TPV implant. Mean age and weight were 24.5 +/- 12 years and 64.3 +/- 20 kg, respectively. Diagnoses were: TOF (53%), D-TGA/DORV (18%), s/p Ross (15%), and Truncus (9%). Types of RV-PA connections were: conduits (96), bioprosthetic valves (14), and other (7). Successful TPV implant occurred in 91 pts (77%). RVOT balloon angioplasty was performed in 43/118 pts (36%). Aortography was performed in 18/43 pts with AD/AI noted in 6/18 (33%); 2 with D-TGA (1 s/p Lecompte, 1 s/p Rastelli), 2 with TOF, 1 Truncus and 1 s/p Ross. Procedure was aborted in the 2 who developed severe AD/AI. TPV was implanted in 3/4 patients with mild AD/AI. Review of pre-post TPV implantation echocardiograms in 83/91 pts (91%) revealed no new/worsened AI in any patient. CONCLUSION: AD/AI is relatively common on aortography during simultaneous RVOT balloon angioplasty. Lack of AI progression by echocardiography post-TPV implant suggests these may be benign findings in most cases. However, AD/AI should be carefully evaluated in certain anatomic subtypes with close RVOT/aortic alignments. PMID- 26822285 TI - Serum Bactericidal Assay: New Role in Salmonella Detection. AB - While inspecting animal feed for Salmonella contamination, we routinely observed bacterial colonies on selective agars that were similar in appearance to those formed by Salmonella. These were identified as Citrobacter freundii, Proteus mirabilis, and Serratia fonticola using biochemical and serological techniques. Because the presence of these bacterial species confounds identification of Salmonella, we refer to them as "interference bacteria." Polyvalent antisera against these interference bacteria were prepared by immunizing rabbits with a mixture of all three organisms. To minimize or eliminate interference by these bacteria, the polyvalent antisera were introduced between the steps of selective enrichment and Salmonella-selective plating. The antisera raised against the interference bacteria, when combined with neonatal rabbit complement, exhibited specific bactericidal activity against C. freundii, P. mirabilis, and S. fonticola. The respective serum bactericidal assay titers were 2(9), 2(8), and 2(10). In selective broth, polyvalent antisera could also kill the target bacterial cells effectively. We tested 526 samples (186 white fishmeal, 97 red fishmeal, and 243 cattle bone powder) using the polyvalent antisera and found that the rates of contamination of each species of the three respective foods decreased by 58.8, 100, and 83%. Our data indicates that polyvalent sera against C. freundii, P. mirabilis, and S. fonticola can be used as inhibitors to increase the accuracy of Salmonella detection. PMID- 26822284 TI - Fragment-Based Protein-Protein Interaction Antagonists of a Viral Dimeric Protease. AB - Fragment-based drug discovery has shown promise as an approach for challenging targets such as protein-protein interfaces. We developed and applied an activity based fragment screen against dimeric Kaposi's sarcoma-associated herpesvirus protease (KSHV Pr) using an optimized fluorogenic substrate. Dose-response determination was performed as a confirmation screen, and NMR spectroscopy was used to map fragment inhibitor binding to KSHV Pr. Kinetic assays demonstrated that several initial hits also inhibit human cytomegalovirus protease (HCMV Pr). Binding of these hits to HCMV Pr was also confirmed by NMR spectroscopy. Despite the use of a target-agnostic fragment library, more than 80 % of confirmed hits disrupted dimerization and bound to a previously reported pocket at the dimer interface of KSHV Pr, not to the active site. One class of fragments, an aminothiazole scaffold, was further explored using commercially available analogues. These compounds demonstrated greater than 100-fold improvement of inhibition. This study illustrates the power of fragment-based screening for these challenging enzymatic targets and provides an example of the potential druggability of pockets at protein-protein interfaces. PMID- 26822286 TI - Interaction between the spectral photon flux density distributions of light during growth and for measurements in net photosynthetic rates of cucumber leaves. AB - The net photosynthetic rate of a leaf becomes acclimated to the plant's environment during growth. These rates are often measured, evaluated and compared among leaves of plants grown under different light conditions. In this study, we compared net photosynthetic rates of cucumber leaves grown under white light emitting diode (LED) light without and with supplemental far-red (FR) LED light (W- and WFR-leaves, respectively) under three different measuring light (ML) conditions: their respective growth light (GL), artificial sunlight (AS) and blue and red (BR) light. The difference in the measured photosynthetic rates between W and WFR-leaves was greater under BR than under GL and AS. In other words, an interaction between supplemental FR light during growth and the spectral photon flux density distribution (SPD) of ML affected the measured net photosynthetic rates. We showed that the comparison and evaluation of leaf photosynthetic rates and characteristics can be biased depending on the SPD of ML, especially for plants grown under different photon flux densities in the FR waveband. We also investigated the mechanism of the interaction. We confirmed that the distribution of excitation energy between the two photosystems (PSs) changed in response to the SPD of GL, and that this change resulted in the interaction, as suggested in previous reports. However, changes in PS stoichiometry could not completely explain the adjustment in excitation energy distribution observed in this study, suggesting that other mechanisms may be involved in the interaction. PMID- 26822287 TI - Porous Organic Polymer Films with Tunable Work Functions and Selective Hole and Electron Flows for Energy Conversions. AB - Organic optoelectronics are promising technologies for energy conversion. However, the electrode interlayer, a key material between active layers and conducting electrodes that controls the transport of charge carriers in and out of devices, is still a chemical challenge. Herein, we report a class of porous organic polymers with tunable work function as hole- and electron-selective electrode interlayers. The network with organoborane and carbazole units exhibits extremely low work-function-selective electron flow; while upon ionic ligation and electro-oxidation, the network significantly increases the work function and turns into hole conduction. We demonstrate their outstanding functions as anode and cathode interlayers in energy-converting solar cells and light-emitting diodes. PMID- 26822288 TI - Highly Efficient Transition Metal Nanoparticle Catalysts in Aqueous Solutions. AB - A ligand design is proposed for transition metal nanoparticle (TMNP) catalysts in aqueous solution. Thus, a tris(triazolyl)-polyethylene glycol (tris-trz-PEG) amphiphilic ligand, 2, is used for the synthesis of very small TMNPs with Fe, Co, Ni, Cu, Ru, Pd, Ag, Pt, and Au. These TMNP-2 catalysts were evaluated and compared for the model 4-nitrophenol reduction, and proved to be extremely efficient. High catalytic efficiencies involving the use of only a few ppm metal of PdNPs, RuNPs, and CuNPs were also exemplified in Suzuki-Miyaura, transfer hydrogenation, and click reactions, respectively. PMID- 26822289 TI - Comparison of clinical and radiographic status of platform-switched implants placed in patients with and without type 2 diabetes mellitus: a 24-month follow up longitudinal study. AB - OBJECTIVE: The purpose of the present 24-month follow-up longitudinal study was to compare the clinical and radiographic status of platform-switched implants placed in patients with and without type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: In total, 45 male non-smokers were included. In Group-1, there were 23 patients with T2DM, and patients in Group-2 comprised of 22 self-reported non diabetic controls. Under local anesthesia, platform-switched implants were placed in the mandible. Peri-implant bleeding on probing (BOP), probing depth (PD), marginal bone loss (MBL) and hemoglobin A1c (HbA1c) levels were measured at 12 and 24 months of follow-up. Participants were also enrolled in a biannual oral hygiene maintenance program. RESULTS: The mean age of participants in groups 1 and 2 were 42.4 years (40-46 years) and 41.8 years (39-44 years), respectively. In Group-1, the mean duration of T2DM was 14.5 +/- 0.7 months. At 12 and 24 months of follow-up, there was no significant difference in the mean HbA1c levels among patients in groups 1 and 2. At 12 and 24 months of follow-up, there was no significant difference in peri-implant BOP, PD and MBL in both groups. CONCLUSIONS: Platform-switched implants can remain clinically and radiographically stable in patients with T2DM in a manner similar to non-diabetic individuals. However, it is emphasized that bone loss around implants is influenced by several factors (such as oral hygiene status, glycemic control and tobacco smoking) and not merely platform switching. PMID- 26822291 TI - 30-Year-Old Man with Head Trauma Three Months Ago. PMID- 26822290 TI - Overexpression of a brassinosteroid biosynthetic gene Dwarf enhances photosynthetic capacity through activation of Calvin cycle enzymes in tomato. AB - BACKGROUND: Genetic manipulation of brassinosteroid (BR) biosynthesis or signaling is a promising strategy to improve crop yield and quality. However, the relationships between the BR-promoted growth and photosynthesis and the exact mechanism of BR-regulated photosynthetic capacity are not clear. Here, we generated transgenic tomato plants by overexpressing Dwarf, a BR biosynthetic gene that encodes the CYP85A1, and compared the photosynthetic capacity with the BR biosynthetic mutant d (im) and wild type. RESULTS: Overexpression of Dwarf promoted net photosynthetic rate (P N), whereas BR deficiency in d (im) led to a significant inhibition in P N as compared with WT. The activation status of RuBisCO, and the protein content and activity of RuBisCO activase, but not the total content and transcripts of RuBisCO were closely related to the endogenous BR levels in different genotypes. However, endogenous BR positively regulated the expression and activity of fructose-1,6-bisphosphatase. Dwarf overexpression enhanced the activity of dehydroascorbate reductase and glutathione reductase, leading to a reduced redox status, whereas BR deficiency had the contrasting effects. In addition, BR induced a reduction of 2-cystein peroxiredoxin without altering the protein content. CONCLUSIONS: BR plays a role in the regulation of photosynthesis. BR can increase the photosynthetic capacity by inducing a reduced redox status that maintains the activation states of Calvin cycle enzymes. PMID- 26822292 TI - Bilateral renal infarction mimicking rapidly progressive glomerulonephritis. PMID- 26822293 TI - Switchable Hydrophobic Valve for Controlled Microfluidic Processing. AB - A simple microfluidic valve, without any moving parts, is presented that can control solution flow on demand in microchannels of many different materials using a low-power electric signal. Many independently operating valves can easily be integrated into complex microfluidic systems. The valve consists of a self assembled monolayer (SAM) formed on a platinum electrode that is incorporated directly in the microchannel. The normally-on valve stops the solution flow due to a hydrophobic SAM on the electrode surface. The solution is allowed to pass the valve by applying a potential to the electrode, which removes the SAM due to reductive desorption. The valve operation is highly stable and has switching times of the order of 1 s. The valve is ideal for controlled solution manipulation in integrated micro-analytical systems and autonomous microfluidic systems. PMID- 26822295 TI - Highly flexible self-powered sensors based on printed circuit board technology for human motion detection and gesture recognition. AB - In this paper, we demonstrate a new integration of printed circuit board (PCB) technology-based self-powered sensors (PSSs) and direct-write, near-field electrospinning (NFES) with polyvinylidene fluoride (PVDF) micro/nano fibers (MNFs) as source materials. Integration with PCB technology is highly desirable for affordable mass production. In addition, we systematically investigate the effects of electrodes with intervals in the range of 0.15 mm to 0.40 mm on the resultant PSS output voltage and current. The results show that at a strain of 0.5% and 5 Hz, a PSS with a gap interval 0.15 mm produces a maximum output voltage of 3 V and a maximum output current of 220 nA. Under the same dimensional constraints, the MNFs are massively connected in series (via accumulation of continuous MNFs across the gaps ) and in parallel (via accumulation of parallel MNFs on the same gap) simultaneously. Finally, encapsulation in a flexible polymer with different interval electrodes demonstrated that electrical superposition can be realized by connecting MNFs collectively and effectively in serial/parallel patterns to achieve a high current and high voltage output, respectively. Further improvement in PSSs based on the effect of cooperativity was experimentally realized by rolling-up the device into a cylindrical shape, resulting in a 130% increase in power output due to the cooperative effect. We assembled the piezoelectric MNF sensors on gloves, bandages and stockings to fabricate devices that can detect different types of human motion, including finger motion and various flexing and extensions of an ankle. The firmly glued PSSs were tested on the glove and ankle respectively to detect and harvest the various movements and the output voltage was recorded as ~1.5 V under jumping movement (one PSS) and ~4.5 V for the clenched fist with five fingers bent concurrently (five PSSs). This research shows that piezoelectric MNFs not only have a huge impact on harvesting various external sources from mechanical energy but also can distinguish different motions as a self-powered active deformation sensor. PMID- 26822296 TI - French parliament passes law to allow sedation at end of life. PMID- 26822294 TI - Genetic determinants of pig birth weight variability. AB - BACKGROUND: Piglet birth weight variability, a trait also known as the within litter homogeneity of birth weight, reflects the sow's prolificacy, because it is positively genetically correlated with preweaning mortality but negatively correlated with the mean growth of piglets during sucking. In addition, the maternal additive genetic variance and heritability has been found exist for this trait, thus, reduction in the variability of piglet birth weight to improve the sow prolificacy is possible by selective breeding. RESULTS: We performed a genome wide association study (GWAS) in 82 sows with extreme standard deviation of birth weights within the first parity to identify significant SNPs, and finally 266 genome-wide significant SNPs (p < 0.01) were identified. These SNPs were mainly enriched on chromosome 7, 1, 13, 14, 15 and 18. We further scanned genes of the top 50 SNPs with the lowest p values and found some genes involved in plasma glucose homeostasis (GLP1R) and lipid metabolism as well as maternal-fetal lipid transport (AACS, APOB, OSBPL10 and LRP1B) which may contribute to the birth weight variability trait. CONCLUSIONS: Birth weight variability trait has a low heritability. It is not easy to get significant signal by GWAS using small sample size. Herein, we identified some candidate chromosome regions especially chromosome 7 and suggested five genes which may provide some information for the further study. PMID- 26822297 TI - Evaluating the effect of three teaching strategies on student nurses' moral sensitivity. AB - BACKGROUND: The Taiwan Nursing Accreditation Council has proposed eight core professional nursing qualities including ethical literacy. Consequently, nursing ethics education is a required course for student nurses. These courses are intended to improve the ethical literacy. Moral sensitivity is the cornerstone of ethical literacy, and learning moral sensitivity is the initial step towards developing ethical literacy. OBJECTIVES: To explore the effect of nursing ethics educational interventions based on multiple teaching strategies on student nurses moral sensitivity. Based on the visual, auditory and kinaesthetic model, three strategies were developed for determining the programme components and corresponding learning styles. RESEARCH DESIGN: This was a quasi-experimental study. PARTICIPANTS: A total of 234 junior-college student nurses participated in this study. All participants were aged 18-19 years. Ethical considerations: The study protocol was approved by the institutional review boards of Kaohsiung Veterans General Hospital. Only the participants who signed an informed consent form took part in the study. The participants were permitted to withdraw from the study at any point if they wished to do so without affecting their academic score. RESULTS: The scores of Modified Moral Sensitivity Questionnaire for Student Nurses were significantly improved after the intervention of integrating multiple teaching strategies ( p = .042). Significant relationships were observed between the satisfaction scores of two teaching strategies and moral sensitivity. The results indicated that using multiple teaching strategies is effective for promoting nursing ethics learning. CONCLUSION: This strategy was consistent with the student nurses' preferred learning style and was used to correct their erroneous ethical conceptions, assisting in developing their ethical knowledge. PMID- 26822298 TI - Personal and professional values held by baccalaureate nursing students. AB - BACKGROUND: Values are ideals and beliefs that individuals and groups uphold and lie at the core of the diverse world of human behaviour and are expressed in every human decision and action, both consciously and unconsciously. They represent basic beliefs of what is right, good or desirable and motivate both personal and professional behaviour. In the context of nursing profession, values are essential in order to maintain high standards of the nursing care. OBJECTIVES: This study was planned to examine changes in nursing students' personal and professional values between entering and graduating from an undergraduate nursing programme. Ethical considerations: Measures to protect participants included obtaining Deaconship of Nursing Faculty approval, obtaining signed informed consent and maintaining confidentiality. METHODS: This study was designed as longitudinal quality. The research population included 143 students registered at a first grade of a nursing faculty for the 2009-2010 academic year. Data were collected with a Questionnaire Form, the Value Preferences Scale, the Professional Values Precedence Scale and the Nursing Professional Values Scale. FINDINGS: According to the results, social values have statistical differences in 4-year nursing education. Nursing students in second class have higher score in terms of social values than those in third class. Also, majority of students ranked human dignity as first and justice as second and third from first to fourth classes, and they have very high scores on Nursing Professional Values Scale and its subscales and stated that all items of Nursing Professional Values Scale are very important. CONCLUSION: As a result, nursing education has vital role in acquiring and maintaining professional values. PMID- 26822299 TI - Effect of patients' rights training sessions for nurses on perceptions of nurses and patients. AB - BACKGROUND: Patients' rights are universal values that must be respected; however, it is not easy to put such values and principles into effect as approaches and attitudes differ from individual to individual, from society to society, and from country to country. If we want to reach a general conclusion about the status of patient rights in the world as whole, we should examine the situation in individual countries. OBJECTIVE: To study the effect of training sessions for nurses about patients' rights on the perceptions of nurses and patients in two Egyptian hospitals. METHODS: Quasi-experimental with pre- and posttest design was used in this study. Two groups of participants were included in the study: the first with 97 nurses and the second with 135 patients. A questionnaire sheet was used for nurses and patients to assess their perceptions about patients' rights before starting sessions. The training sessions were developed based on the baseline information gathered in the assessment phase and related literature. After the implementation of the sessions, a posttest was immediately conducted for nurses, while for patients the posttest was conducted 1 month after implementation to evaluate the effect of the nurses' training sessions on the patients' perceptions. The same tools were used in pretest and posttest. Ethical considerations: Written approval was sought and obtained from the administrators of the studied hospitals prior to conducting the study. Oral consent was obtained from nurses and patients willing to participate. Confidentiality and anonymity of the participants were strictly maintained through code numbers on the questionnaires. RESULTS: The improvement in nurses' knowledge and perceptions about patients' rights after implementation of the training sessions was remarkable. Moreover, an improvement in patients' perceptions regarding their rights was reported. CONCLUSION: Repetition of the training sessions is suggested to achieve continuous improvement. Provision of posters and booklets about a bill of patient rights within the hospitals and conduction of further study to examine nurses' performance and patients' satisfaction based on code of ethics are recommended. PMID- 26822300 TI - Nursing students' perceptions of faculty members' ethical/unethical attitudes. AB - BACKGROUND: Through education, individuals acquire knowledge, skill and attitudes that facilitate professional socialization; it involves intellectual, emotional and psychomotor skill development. Teachers are role models for behaviour modification and value development. OBJECTIVE: To examine students' perceptions of faculty members' ethical and unethical attitudes during interactions in undergraduate nursing. RESEARCH DESIGN: This descriptive study consisted of two phases. In Phase I, we developed an instrument, which was administered to nursing students to assess validity and reliability. Exploratory factor analysis yielded 32 items. Cronbach's alpha was 0.83, and test-retest reliability was good. In Phase II, a 32-item version of the instrument was administered to nursing students from another university. Participants and research context: Participants included 219 nursing students from one university in Phase I and 196 from another university in Phase II. The study was conducted at the universities attended by the participants. Ethical considerations: Ethical approval was granted by the institutions involved, and all participants provided informed consent. FINDINGS: In Phase I, the instrument demonstrated good psychometric properties for measuring nursing students' perceptions of faculty members' ethical and unethical behaviours. In Phase II, students considered certain professional and personal qualities, including respecting confidentiality and students' private lives and assuming an impartial stance during interactions in the classroom, examinations, or clinical practice, ethical. They considered using obscene examples or unprofessional speech during teaching, selling textbooks in class, using university facilities for personal interests, engaging in romantic relationships with students, and humiliating students in front of patients or staff in clinical settings unethical. CONCLUSION: Results of this study suggest that nurse educators should be aware of their critical role in the teaching-learning process, and they must scrutinize their attitudes towards students from an ethical point of view. PMID- 26822301 TI - Religion, Judaism, and the challenge of maintaining an adequately immunized population. AB - A slow but steady trend to decline routine immunization has evolved over the past few decades, despite its pivotal role in staving off life-threatening communicable diseases. Religious beliefs are among the reasons given for exemptions. In the context of an overview of various religious approaches to this issue, this article addresses the Jewish religious obligation to immunize. The latter is nested in the more general obligation to take responsibility for one's health as it is essential to living a morally productive life. Furthermore, the individual's responsibility extends to supporting communal health by contributing to herd immunity. Judaism embraces evidence-based information regarding immunization safety and efficacy and holds the resulting professional guidelines to be religiously binding. From a Jewish perspective, government bodies need to weigh respect for individual autonomy to refrain from immunization against preserving public safety, such that waiving autonomy should be reserved for immediately life-threatening situations. Nurses' knowledge and understanding of the Jewish legal approach as explicated in this article and those of other religions in which similar principles apply (such as Islam and Christianity) can enrich their awareness of how revering God can go hand in hand with an obligation to prevent illness for the self and the community by immunizing. PMID- 26822302 TI - Nurses' role and care practices in decision-making regarding artificial ventilation in late stage pulmonary disease. AB - BACKGROUND: Decisions regarding whether or not to institute mechanical ventilation during the later stages of chronic obstructive pulmonary disease is challenging both ethically, emotionally and medically. Caring for these patients is a multifaceted process where nurses play a crucial role. Research question and design: We have investigated how nurses experienced their own role in decision making processes regarding mechanical ventilation in later stages of chronic obstructive pulmonary disease and how they consider the patients' role in these processes. We applied a qualitative approach, with six focus-group interviews of nurses (n = 26). Ethical considerations: The Regional Committees for Medical and Health Research Ethics approved the study. Voluntary informed consent was obtained. FINDINGS: The nurses found themselves operating within a cure-directed treatment culture wherein they were unable to stand up for the caring values. They perceived their roles and responsibilities in decision-making processes regarding mechanical ventilation to patients as unclear and unsatisfactory. They also experienced inadequate interdisciplinary cooperation. DISCUSSION: Lack of communication skills, the traditional hierarchical hospital culture together with operating in a medical-orientated treatment culture where caring values is rated as less important might explain the nurses' absence in participation in the decision about mechanical ventilation. CONCLUSION: To be able to advocate for the patients' and their own right to be included in decision-making processes, nurses need an awareness of their own responsibilities. This requires personal courage, leadership who are capable of organising common interpersonal meetings and willingness on the part of the physicians to include and value the nurses' participation in decision-making processes. PMID- 26822303 TI - Arrhythmogenesis in Timothy Syndrome is associated with defects in Ca(2+) dependent inactivation. AB - Timothy Syndrome (TS) is a multisystem disorder, prominently featuring cardiac action potential prolongation with paroxysms of life-threatening arrhythmias. The underlying defect is a single de novo missense mutation in CaV1.2 channels, either G406R or G402S. Notably, these mutations are often viewed as equivalent, as they produce comparable defects in voltage-dependent inactivation and cause similar manifestations in patients. Yet, their effects on calcium-dependent inactivation (CDI) have remained uncertain. Here, we find a significant defect in CDI in TS channels, and uncover a remarkable divergence in the underlying mechanism for G406R versus G402S variants. Moreover, expression of these TS channels in cultured adult guinea pig myocytes, combined with a quantitative ventricular myocyte model, reveals a threshold behaviour in the induction of arrhythmias due to TS channel expression, suggesting an important therapeutic principle: a small shift in the complement of mutant versus wild-type channels may confer significant clinical improvement. PMID- 26822304 TI - Age-related changes in behavior in C57BL/6J mice from young adulthood to middle age. AB - BACKGROUND: Aging is considered to be associated with progressive changes in the brain and its associated sensory, motor, and cognitive functions. A large number of studies comparing young and aged animals have reported differences in various behaviors between age-cohorts, indicating behavioral dysfunctions related to aging. However, relatively little is known about behavioral changes from young adulthood to middle age, and the effect of age on behavior during the early stages of life remains to be understood. In order to investigate age-related changes in the behaviors of mice from young adulthood to middle age, we performed a large-scale analysis of the behavioral data obtained from our behavioral test battery involving 1739 C57BL/6J wild-type mice at 2-12 months of age. RESULTS: Significant behavioral differences between age groups (2-3-, 4-5-, 6-7-, and 8-12 month-old groups) were found in all the behavioral tests, including the light/dark transition, open field, elevated plus maze, rotarod, social interaction, prepulse inhibition, Porsolt forced swim, tail suspension, Barnes maze, and fear conditioning tests, except for the hot plate test. Compared with the 2-3-month-old group, the 4-5- and 6-7-month-old groups exhibited decreased locomotor activity to novel environments, motor function, acoustic startle response, social behavior, and depression-related behavior, increased prepulse inhibition, and deficits in spatial and cued fear memory. For most behaviors, the 8-12-month-old group showed similar but more pronounced changes in most of these behaviors compared with the younger age groups. Older groups exhibited increased anxiety-like behavior in the light/dark transition test whereas those groups showed seemingly decreased anxiety-like behavior measured by the elevated plus maze test. CONCLUSIONS: The large-scale analysis of behavioral data from our battery of behavioral tests indicated age-related changes in a wide range of behaviors from young adulthood to middle age in C57BL/6J mice, though these results might have been influenced by possible confounding factors such as the time of day at testing and prior test experience. Our results also indicate that relatively narrow age differences can produce significant behavioral differences during adulthood in mice. These findings provide an insight into our understanding of the neurobiological processes underlying brain function and behavior that are subject to age-related changes in early to middle life. The findings also indicate that age is one of the critical factors to be carefully considered when designing behavioral tests and interpreting behavioral differences that might be induced by experimental manipulations. PMID- 26822305 TI - Loss of Mrp1 Potentiates Doxorubicin-Induced Cytotoxicity in Neonatal Mouse Cardiomyocytes and Cardiac Fibroblasts. AB - Doxorubicin (DOX) induces dose-dependent cardiotoxicity in part due to its ability to induce oxidative stress. We showed that loss of multidrug resistance associated protein 1 (Abcc1/Mrp1) potentiates DOX-induced cardiac dysfunction in mice in vivo Here, we characterized DOX toxicity in cultured cardiomyocytes (CM) and cardiac fibroblasts (CF) derived from C57BL wild type (WT) and Mrp1 null (Mrp1-/-) neonatal mice. CM accumulated more intracellular DOX relative to CF but this accumulation did not differ between genotypes. Following DOX (0.3-4 MUM), Mrp1-/- CM, and CF, especially CM, showed a greater decrease in viability and increased apoptosis and DNA damage, demonstrated by higher caspase 3 cleavage, poly (ADP-ribose) polymerase 1 (PARP) cleavage and phosphorylated histone H2AX (gammaH2AX) levels versus WT cells. Saline- and DOX-treated Mrp1-/- cells had significantly higher intracellular GSH and GSSG compared with WT cells (P < .05), but the redox potential (Eh) of the GSH/GSSG pool did not differ between genotypes in CM and CF, indicating that Mrp1-/- cells maintain this major redox couple. DOX increased expression of the rate-limiting GSH synthesis enzyme glutamate-cysteine ligase catalytic (GCLc) and regulatory subunits (GCLm) to a significantly greater extent in Mrp1-/- versus WT cells, suggesting adaptive responses to oxidative stress in Mrp1-/- cells that were inadequate to afford protection. Expression of extracellular superoxide dismutase (ECSOD/SOD3) was lower (P < .05) in Mrp1-/- versus WT CM treated with saline (62% +/- 8% of WT) or DOX (43% +/- 12% of WT). Thus, Mrp1 protects CM in particular and CF against DOX induced toxicity, potentially by regulating extracellular redox states. PMID- 26822306 TI - Immunomodulation By Subchronic Low Dose 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Experimental Autoimmune Encephalomyelitis in the Absence of Pertussis Toxin. AB - Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder, characterized by demyelination of neurons in the central nervous system. To investigate the pathogenicity of various T cell types in MS, especially IFN-gamma or IL-17-producing CD4(+ )cells (TH1 or TH17 cells, respectively), the mouse model, experimental autoimmune encephalomyelitis (EAE), is commonly used. One method by which EAE is induced is immunization with myelin oligodendrocyte glycoprotein (MOG) peptide (MOG35-55) followed by subsequent injections of pertussis toxin (PTX) as an adjuvant. We have an interest in the mechanisms by which EAE occurs in the absence of PTX because it induces a milder disease state more consistent with autoimmune disease onset and PTX inactivates Gi/o protein coupled receptors, many of which contribute to immune homeostasis. Another receptor that plays a role in immune homeostasis is the aryl hydrocarbon receptor (AHR). In fact, the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to attenuate EAE pathogenesis by affecting CD4(+ )T and regulatory T (Treg) cells in an AHR-dependent manner. However, many of these studies have been conducted with an acute high dose TCDD. Thus, the goal of this work was to investigate the modulation of MOG-specific immune responses with subchronic low dose TCDD (0.1-1.0 MUg/kg/d for 12 days) in EAE without PTX. The results demonstrate that subchronic, low dose exposure of TCDD attenuates the immune responses in EAE development in the absence of PTX, which is due in part to suppression of MOG-specific IL-17A and IFN-gamma responses. PMID- 26822309 TI - Ru/Al Multilayers Integrate Maximum Energy Density and Ductility for Reactive Materials. AB - Established and already commercialized energetic materials, such as those based on Ni/Al for joining, lack the adequate combination of high energy density and ductile reaction products. To join components, this combination is required for mechanically reliable bonds. In addition to the improvement of existing technologies, expansion into new fields of application can also be anticipated which triggers the search for improved materials. Here, we present a comprehensive characterization of the key parameters that enables us to classify the Ru/Al system as new reactive material among other energetic systems. We finally found that Ru/Al exhibits the unusual integration of high energy density and ductility. For example, we measured reaction front velocities up to 10.9 (+/- 0.33) ms(-1) and peak reaction temperatures of about 2000 degrees C indicating the elevated energy density. To our knowledge, such high temperatures have never been reported in experiments for metallic multilayers. In situ experiments show the synthesis of a single-phase B2-RuAl microstructure ensuring improved ductility. Molecular dynamics simulations corroborate the transformation behavior to RuAl. This study fundamentally characterizes a Ru/Al system and demonstrates its enhanced properties fulfilling the identification requirements of a novel nanoscaled energetic material. PMID- 26822308 TI - A direct interaction between NQO1 and a chemotherapeutic dimeric naphthoquinone. AB - BACKGROUND: Multimeric naphthoquinones are redox-active compounds that exhibit antineoplastic, antiprotozoal, and antiviral activities. Due to their multimodal effect on perturbation of cellular oxidative state, these compounds hold great potential as therapeutic agents against highly proliferative neoplastic cells. In our previous work, we developed a series of novel dimeric naphthoquinones and showed that they were selectively cytotoxic to human acute myeloid leukemia (AML), breast and prostate cancer cell lines. We subsequently identified the oxidoreductase NAD(P)H dehydrogenase, quinone 1 (NQO1) as the major target of dimeric naphthoquinones and proposed a mechanism of action that entailed induction of a futile redox cycling. RESULTS: Here, for the first time, we describe a direct physical interaction between the bromohydroxy dimeric naphthoquinone E6a and NQO1. Moreover, our studies reveal an extensive binding interface between E6a and the isoalloxazine ring of the flavin adenine dinucleotide (FAD) cofactor of NQO1 in addition to interactions with protein side chains in the active site. We also present biochemical evidence that dimeric naphthoquinones affect the redox state of the FAD cofactor of NQO1. Comparison of the mode of binding of E6a with those of other chemotherapeutics reveals unique characteristics of the interaction that can be leveraged in future drug optimization efforts. CONCLUSION: The first structure of a dimeric naphthoquinone NQO1 complex was reported, which can be used for design and synthesis of more potent next generation dimeric naphthoquinones to target NQO1 with higher affinity and specificity. PMID- 26822310 TI - Effective As(III) Removal by A Multi-Charged Hydroacid Complex Draw Solute Facilitated Forward Osmosis-Membrane Distillation (FO-MD) Processes. AB - Effective removal of As(III) from water by an oxalic acid complex with the formula of Na3[Cr(C2O4)3] (Na-Cr-OA) is demonstrated via an forward osmosis membrane distillation (FO-MD) hybrid system in this study. Na-Cr-OA first proved its superiority as a draw solute with high water fluxes and negligible reverse fluxes in FO, then a systematic investigation of the Na-Cr-OA promoted FO process was conducted to ascertain the factors in As(III) removal. Relatively high water fluxes of 28 LMH under the FO mode and 74 LMH under the pressure retarded osmosis (PRO) mode were achieved when using a 1000 ppm As(III) solution as the feed and 1.0 M Na-Cr-OA as the draw solution at 60 degrees C. As(III) removal with a water recovery up to 21.6% (FO mode) and 48.3% (PRO mode) were also achieved in 2 h. An outstanding As(III) rejection with 30-3000 MUg/L As(III) in the permeate was accomplished when As(III) feed solutions varied from 5 * 10(4) to 1 * 10(6) MUg/L, superior to the best FO performance reported for As(III) removal. Incorporating MD into FO not only makes As(III) removal sustainable by reconcentrating the Na-Cr-OA solution simultaneously, but also reduces the As(III) concentration below 10 MUg/L in the product water, meeting the WHO standard. PMID- 26822307 TI - Missing link between microRNA and prostate cancer. AB - MicroRNAs are the non-coding RNAs which regulate endogenous gene expression in animal and plant cells. Alterations in the level of micro-ribonucleic acids (miRNAs) involving the deletions, overexpression, mutations, epigenetic silencing, or dysregulation of transcription factors that target specific miRNAs may culminate in various diseases including cancer. Recent findings demonstrate the role of miRNAs in prostate cancer. Numerous discoveries of miRNAs have marked the research and development surrounding prostate cancer management, diagnosis, and therapy which has made prediction easy, but the effective treatment strategy remains a mystery. This review seeks to draw a link between miRNA and prostate cancer through an understanding of the numerous signaling pathways that these miRNAs control, which may prove to be helpful in identifying therapeutically interesting molecular targets. PMID- 26822312 TI - From cotton mills to composites; has the world of work really changed? PMID- 26822311 TI - Polypharmacy in chronic diseases-Reduction of Inappropriate Medication and Adverse drug events in older populations by electronic Decision Support (PRIMA eDS): study protocol for a randomized controlled trial. AB - BACKGROUND: Multimorbidity is increasing in aging populations with a corresponding increase in polypharmacy as well as inappropriate prescribing. Depending on definitions, 25-50 % of patients aged 75 years or older are exposed to at least five drugs. Evidence is increasing that polypharmacy, even when guidelines advise the prescribing of each drug individually, can potentially cause more harm than benefit to older patients, due to factors such as drug-drug and drug-disease interactions. Several approaches reducing polypharmacy and inappropriate prescribing have been proposed, but evidence showing a benefit of these measures regarding clinically relevant endpoints is scarce. There is an urgent need to implement more effective strategies. We therefore set out to develop an evidence-based electronic decision support (eDS) tool to aid physicians in reducing inappropriate prescribing and test its effectiveness in a large-scale cluster-randomized controlled trial. METHODS: The "Polypharmacy in chronic diseases-Reduction of Inappropriate Medication and Adverse drug events in older populations" (PRIMA)-eDS tool is a tool comprising an indication check and recommendations for the reduction of polypharmacy and inappropriate prescribing based on systematic reviews and guidelines, the European list of inappropriate medications for older people, the SFINX-database of interactions, the PHARAO database on adverse effects, and the RENBASE-database on renal dosing. The tool will be evaluated in a cluster-randomized controlled trial involving 325 general practitioners (GPs) and around 3500 patients across five study centres in the United Kingdom, Germany, Austria and Italy. GP practices will be asked to recruit 11 patients aged 75 years or older who are taking at least eight medications and will be cluster-randomized after completion of patient recruitment. Intervention GPs will have access to the PRIMA-eDS tool, while control GPs will treat their patients according to current guidelines (usual care) without access to the PRIMA eDS tool. After an observation time of 2 years, intervention and control groups will be compared regarding the primary composite endpoint of first non-elective hospitalization or death. DISCUSSION: The principal hypothesis is that reduction of polypharmacy and inappropriate prescribing can improve the clinical composite outcome of hospitalization or death. A positive result of the trial will contribute substantially to the improvement of care in multimorbidity. The trial is necessary to investigate not only whether the reduction of polypharmacy improves outcome, but also whether GPs and patients are willing to follow the recommendations of the PRIMA-eDS tool. TRIAL REGISTRATION: This trial has been registered with Current Controlled Trials Ltd. on 31 July 2014 (ISRCTN10137559). PMID- 26822314 TI - Comments on the causation of malignant mesothelioma: rebutting the false concept that recent exposures to asbestos do not contribute to causation of mesothelioma. AB - The Collegium Ramazzini is an international scientific society that examines critical issues in occupational and environmental medicine with a view towards action to prevent disease and promote health. The Collegium derives its name from Bernardino Ramazzini, the father of occupational medicine, a professor of medicine of the Universities of Modena and Padua in the late 1600s and the early 1700s. The Collegium is comprised of 180 physicians and scientists from 35 countries, each of whom is elected to membership. The Collegium is independent of commercial interests. PMID- 26822313 TI - The global health dimensions of asbestos and asbestos-related diseases. AB - The Collegium Ramazzini is an international scientific society that examines critical issues in occupational and environmental medicine with a view towards action to prevent disease and promote health. The Collegium derives its name from Bernardino Ramazzini, the father of occupational medicine, a professor of medicine of the Universities of Modena and Padua in the late 1600s and the early 1700s. The Collegium is comprised of 180 physicians and scientists from 35 countries, each of whom is elected to membership. The Collegium is independent of commercial interests. PMID- 26822315 TI - Comments on the 2014 Helsinki consensus report on asbestos. AB - The Collegium Ramazzini is an international scientific society that examines critical issues in occupational and environmental medicine with a view towards action to prevent disease and promote health. The Collegium derives its name from Bernardino Ramazzini, the father of occupational medicine, a professor of medicine of the Universities of Modena and Padua in the late 1600s and the early 1700s. The Collegium is comprised of 180 physicians and scientists from 35 countries, each of whom is elected to membership. The Collegium is independent of commercial interests. PMID- 26822316 TI - Metabolomics in amyotrophic lateral sclerosis: how far can it take us? AB - Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease. Alongside identification of aetiologies, development of biomarkers is a foremost research priority. Metabolomics is one promising approach that is being utilized in the search for diagnosis and prognosis markers. Our aim is to provide an overview of the principal research in metabolomics applied to ALS. References were identified using PubMed with the terms 'metabolomics' or 'metabolomic' and 'ALS' or 'amyotrophic lateral sclerosis' or 'MND' or 'motor neuron disorders'. To date, nine articles have reported metabolomics research in patients and a few additional studies examined disease physiology and drug effects in patients or models. Metabolomics contribute to a better understanding of ALS pathophysiology but, to date, no biomarker has been validated for diagnosis, principally due to the heterogeneity of the disease and the absence of applied standardized methodology for biomarker discovery. A consensus on best metabolomics methodology as well as systematic independent validation will be an important accomplishment on the path to identifying the long-awaited biomarkers for ALS and to improve clinical trial designs. PMID- 26822317 TI - Therapeutically targeting SELF-reinforcing leukemic niches in acute myeloid leukemia: A worthy endeavor? AB - A tight relationship between the acute myeloid leukemia (AML) population and the bone marrow (BM) microenvironment has been convincingly established. The AML clone contains leukemic stem cells (LSCs) that compete with normal hematopoietic stem cells (HSCs) for niche occupancy and remodel the niche; whereas, the BM microenvironment might promote AML development and progression not only through hypoxia and homing/adhesion molecules, but also through genetic defects. Although it is still unknown whether the niche influences treatment results or contains any potential target for treatment, this dynamic AML-niche interaction might be a promising therapeutic objective to significantly improve the AML cure rate. PMID- 26822318 TI - Synthesis and fungicidal activity of novel 2,5-disubstituted-1,3,4- thiadiazole derivatives containing 5-phenyl-2-furan. AB - A series of 2,5-disubstituted-1,3,4-thiadiazoles were synthesized using Lawesson's reagent by an efficient approach under microwave irradiation in good yields. Their structures were characterized by MS, IR, (1)H NMR, (13)C NMR, and elemental analysis. Their in vitro and in vivo fungicidal activities revealed that the title compounds exhibited considerable activity against five selected fungi, especially to Phytophthora infestans. In order to illustrate the mechanism of title compounds against P. infestans, scanning electron micrographs (SEM) and transmission electron micrographs (TEM) were applied. The morphological and ultrastructural studies demonstrated that compound I18 led to swelling of hyphae, thickening and proliferating multilayer cell walls, excessive septation and accumulation of dense bodies. The bioassay results indicated compound I18 might act on cell wall biosynthesis, and blocked the nutrition transportation and led to cells senescence and death. Meanwhile, compound I18 had broad fungicidal activity against other twenty different kinds of fungi. These results suggested that title compounds were eligible to be development candidates and compound I18 as a promising lead compound was worthy to be further discovery, especially against P. infestans. PMID- 26822320 TI - Application of natural deep eutectic solvents to the extraction of anthocyanins from Catharanthus roseus with high extractability and stability replacing conventional organic solvents. AB - Natural deep eutectic solvents (NADES) have attracted a great deal of attention in recent times as promising green media. They are generally composed of neutral, acidic or basic compounds that form liquids of high viscosity when mixed in certain molar ratio. Despite their potential, viscosity and acid or basic nature of some ingredients may affect the extraction capacity and stabilizing ability of the target compounds. To investigate these effects, extraction with a series of NADES was employed for the analysis of anthocyanins in flower petals of Catharanthus roseus in combination with HPLC-DAD-based metabolic profiling. Along with the extraction yields of anthocyanins their stability in NADES was also studied. Multivariate data analysis indicates that the lactic acid-glucose (LGH), and 1,2-propanediol-choline chloride (PCH) NADES present a similar extraction power for anthocyanins as conventional organic solvents. Furthermore, among the NADES employed, LGH exhibits an at least three times higher stabilizing capacity for cyanidins than acidified ethanol, which facilitates their extraction and analysis process. Comparing NADES to the conventional organic solvents, in addition to their reduced environmental impact, they proved to provide higher stability for anthocyanins, and therefore have a great potential as possible alternatives to those organic solvents in health related areas such as food, pharmaceuticals and cosmetics. PMID- 26822319 TI - Targeted Therapies for the Treatment of Brain Metastases in Solid Tumors. AB - Brain metastases are a major cause of morbidity and mortality in cancer patients. While the mainstay treatment comprises surgery and radiation therapy, the role of systemic agents remains controversial. In general, it has been presumed that poor blood-brain barrier (BBB) penetration and inherently more resistant metastatic brain disease preclude a favorable systemic treatment approach. However, a better understanding of tumor biology and the subsequent development of targeted drugs have reawakened interest in systemic therapy. Despite still limited brain distribution, a variety of targeted drugs have demonstrated activity in brain metastases in early clinical trials. Nevertheless, disease progression commonly occurs, and it remains to be elucidated whether limited CNS drug distribution or the acquisition of resistant metastatic clones must be held responsible for this prognosis. Moreover, micrometastatic brain disease beyond an intact BBB-and ultimately prevention of brain metastasis formation-may generally remain inaccessible for first-generation targeted agents with poor CNS penetration. To overcome limited brain distribution and possibly emerging acquired resistance, highly potent next-generation targeted drugs with enhanced CNS distribution have been developed. In view of this emerging but yet undefined role of targeted therapies in the treatment of brain metastases from solid tumors, this review aims to summarize the current knowledge from clinical trials and discusses clinically relevant obstacles to overcome. PMID- 26822322 TI - A novel virus from Macrosiphum euphorbiae with similarities to members of the family Flaviviridae. AB - A virus with a large genome was identified in the transcriptome of the potato aphid (Macrosiphum euphorbiae) and was named Macrosiphum euphorbiae virus 1 (MeV 1). The MeV-1 genome is 22 780 nt in size, including 3' and 5' non-coding regions, with a single large ORF encoding a putative polyprotein of 7333 aa. The C-terminal region of the predicted MeV-1 polyprotein contained sequences with similarities to helicase, methyltransferase and RNA-dependent RNA polymerase (RdRp) motifs, while the N-terminal region lacked any motifs including structural proteins. Phylogenetic analysis of the helicase placed MeV-1 close to pestiviruses, while the RdRp region placed it close to pestiviruses and flaviviruses, suggesting MeV-1 has a positive-polarity ssRNA genome and is a member of the family Flaviviridae. Since the MeV-1 genome is predicted to contain a methyltransferase, a gene present typically in flaviviruses but not pestiviruses, MeV-1 is likely a member of the genus Flavivirus. MeV-1 was present in nymphal and adult stages of the aphid, aphid saliva and plant tissues fed upon by aphids. However, the virus was unable to multiply and spread in tomato plants. In addition, dsRNA, the replication intermediate of RNA viruses, was isolated from virus-infected M. euphorbiae and not from tomato plants infested with the aphid. Furthermore, nymphs laid without exposure to infected plants harboured the virus, indicating that MeV-1 is an aphid-infecting virus likely transmitted transovarially. The virus was present in M. euphorbiae populations from Europe but not from North America and was absent in all other aphid species tested. PMID- 26822321 TI - Complement component C3a plays a critical role in endothelial activation and leukocyte recruitment into the brain. AB - BACKGROUND: The complement system is becoming increasingly recognized as a key participant in many neurodegenerative diseases of the brain. Complement-deficient animals exhibit reduced neuroinflammation. METHODS: In the present study, we administered intracerebroventricularly lipopolysaccharide (LPS) to mimic local infection of the brain and investigated the role of key complement component C3 in brain vasculature endothelial activation and leukocyte recruitment. The degree of neutrophil infiltration was determined by esterase staining. Leukocyte endothelial interactions were measured using intravital microscopy. Cerebral endothelial activation was evaluated using real-time PCR and Western blotting. RESULTS: Neutrophil infiltration into the brain cortex and hippocampus was significantly reduced in C3(-/-) mice and C3aR(-/-) mice but not in C6(-/-) mice. We detected markedly attenuated leukocyte-endothelial interactions in the brain microvasculature of C3(-/-) mice. Accordingly, in response to LPS administration, the brain microvasculature in these mice had decreased expression of P-selectin, E-selectin, intercellular cell adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Depletion of C3 from the circulation also caused reduction in VCAM-1 and E-selectin expression and leukocyte recruitment, suggesting that C3 in the circulation contributed to brain endothelial activation. Furthermore, C3(-/-) mice exhibited decreased leukocyte recruitment into the brain upon tumor necrosis factor-alpha (TNF-alpha) stimulation. C3a activated the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) and induced the upregulation of VCAM-1 and ICAM 1 expression in murine primary cerebral endothelial cells in vitro. CONCLUSIONS: Our study provides the first evidence that C3a plays a critical role in cerebral endothelial activation and leukocyte recruitment during inflammation in the brain. PMID- 26822323 TI - Monitoring of minimal residual disease in early T-cell precursor acute lymphoblastic leukaemia by next-generation sequencing. PMID- 26822325 TI - Folic Acid Supplement Intake in Early Pregnancy Increases Risk of Gestational Diabetes Mellitus: Evidence From a Prospective Cohort Study. PMID- 26822324 TI - Sitagliptin Attenuates the Progression of Carotid Intima-Media Thickening in Insulin-Treated Patients With Type 2 Diabetes: The Sitagliptin Preventive Study of Intima-Media Thickness Evaluation (SPIKE): A Randomized Controlled Trial. AB - OBJECTIVE: The effect of additional treatment with oral hypoglycemic agents on the progression of atherosclerosis remains unknown in insulin-treated patients with type 2 diabetes mellitus (T2DM). We assessed the effects of sitagliptin, a dipeptidyl peptidase 4 inhibitor, on carotid intima-media thickness (IMT) in T2DM. RESEARCH DESIGN AND METHODS: This prospective, randomized, open-label, blinded end point, multicenter, parallel-group, comparative study included 282 insulin-treated patients with T2DM free of a history of apparent cardiovascular diseases who were recruited at 12 clinical units and randomly allocated to either the sitagliptin group (n = 142) or the control group (n = 140). The primary outcomes were changes in mean and maximum IMT of the common carotid artery measured by echography at the end of a 104-week treatment period. RESULTS: Sitagliptin had a more potent glucose-lowering effect compared with the conventional treatment (-0.5 +/- 1.0% vs. -0.2 +/- 0.9%; P = 0.004), without increasing hypoglycemic episodes or body weight. Changes in the mean and left maximum IMT, but not right maximum IMT, of the common carotid arteries were significantly greater after sitagliptin treatment compared with conventional treatment (-0.029 [SE 0.013] vs. 0.024 [0.013] mm [P = 0.005]; -0.065 [0.027] vs. 0.022 [0.026] mm [P = 0.021]; -0.007 [0.031] vs. 0.027 [0.031] mm [P = 0.45], respectively). Over 104 weeks, sitagliptin, but not conventional treatment, significantly reduced the mean IMT and left maximum IMT of common carotid arteries relative to the baseline. CONCLUSIONS: Sitagliptin attenuated the progression of carotid IMT in insulin-treated patients with T2DM free of apparent cardiovascular disease compared with conventional treatment. PMID- 26822327 TI - Incidence and Clinical Features of Diabetic Ketoacidosis After Bariatric and Metabolic Surgery. PMID- 26822326 TI - Nine-Year Effects of 3.7 Years of Intensive Glycemic Control on Cardiovascular Outcomes. AB - OBJECTIVE: In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, ~4 years of intensive versus standard glycemic control in participants with type 2 diabetes and other cardiovascular risk factors had a neutral effect on the composite cardiovascular outcome, increased cardiovascular and total mortality, and reduced nonfatal myocardial infarction. Effects of the intervention during prolonged follow-up were analyzed. RESEARCH DESIGN AND METHODS: All surviving ACCORD participants were invited to participate in the ACCORD Follow-on (ACCORDION) study, during which participants were treated according to their health care provider's judgment. Cardiovascular and other health-related outcomes were prospectively collected and analyzed using an intention-to-treat approach according to the group to which participants were originally allocated. RESULTS: A total of 8,601 people, representing 98% of those who did not suffer a primary outcome or death during the ACCORD trial, were monitored for a median of 8.8 years and a mean of 7.7 years from randomization. Intensive glucose lowering for a mean of 3.7 years had a neutral long-term effect on the primary composite outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), death from any cause, and an expanded composite outcome that included all-cause death. Moreover, the risk of cardiovascular mortality noted during the active phase (hazard ratio 1.49; 95% CI 1.19, 1.87; P < 0.0001) decreased (HR 1.20; 95% CI 1.03, 1.39; P = 0.02). CONCLUSIONS: In high risk people with type 2 diabetes monitored for 9 years, a mean of 3.7 years of intensive glycemic control had a neutral effect on death and nonfatal cardiovascular events but increased cardiovascular-related death. PMID- 26822328 TI - Encouraging Physical Activity in Patients With Diabetes Through Automatic Personalized Feedback via Reinforcement Learning Improves Glycemic Control. PMID- 26822329 TI - An ion signal responsive dynamic protein nano-spring constructed by high ordered host-guest recognition. AB - A protein self-assembly nano-spring was developed through host-guest interactions between cucurbit[8]uril and tripeptide FGG tags of fusion protein FGG-recoverin GST. Fine control of the conformational changes of the Ca(2+)-responsive domain allows for a 50% stretch of the protein nano-spring as it switches from the contracted state to the extended state. PMID- 26822331 TI - Dark-field differential dynamic microscopy. AB - Differential dynamic microscopy (DDM) is an emerging technique to measure the ensemble dynamics of colloidal and complex fluid motion using optical microscopy in systems that would otherwise be difficult to measure using other methods. To date, DDM has successfully been applied to linear space invariant imaging modes including bright-field, fluorescence, confocal, polarised, and phase-contrast microscopy to study diverse dynamic phenomena. In this work, we show for the first time how DDM analysis can be extended to dark-field imaging, i.e. a linear space variant (LSV) imaging mode. Specifically, we present a particle-based framework for describing dynamic image correlations in DDM, and use it to derive a correction to the image structure function obtained by DDM that accounts for scatterers with non-homogeneous intensity distributions as they move within the imaging plane. To validate the analysis, we study the Brownian motion of gold nanoparticles, whose plasmonic structure allows for nanometer-scale particles to be imaged under dark-field illumination, in Newtonian liquids. We find that diffusion coefficients of the nanoparticles can be reliably measured by dark field DDM, even under optically dense concentrations where analysis via multiple particle tracking microrheology fails. These results demonstrate the potential for DDM analysis to be applied to linear space variant forms of microscopy, providing access to experimental systems unavailable to other imaging modes. PMID- 26822330 TI - Seasonal variation of pharmaceutical concentrations in a river/lake system in Eastern Finland. AB - In this study, the concentrations of 15 pharmaceuticals were monitored during four seasons (February, May, July, and November 2010) along a 32 km stretch of a highly wastewater polluted watercourse (River Rakkolanjoki, Lake Haapajarvi) in Eastern Finland. The aim was to study the seasonal variation in the elimination of the pharmaceuticals and the stability of the compounds along the watercourse. The analysis was carried out using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method combined with extraction and preconcentration on HLB solid phase extraction (SPE) cartridges. Pharmaceutical concentrations were determined at 9 points along the watercourse, and loads and removal of parent compounds were calculated using flow data from the discharge point and the last sampling point. The pharmaceuticals were found in concentrations ranging from low ng l(-1) to low MUg l(-1) values at the discharge point and at concentrations of 0-556 ng l(-1) at the last sampling point. The rate of elimination of the pharmaceutical load was significantly higher in May and July than in February and November. There were clear differences in the stability of the individual compounds along the watercourse. Carbamazepine was not eliminated during any season, while ibuprofen, ketoprofen and sertraline were fully eliminated over the studied stretch of river during the summer months. Other compounds showed continuous elimination independent of the season, indicating different elimination paths, such as sorption, biodegradation and phototransformation, for the studied compounds. PMID- 26822332 TI - Muscle contraction phenotypic analysis enabled by optogenetics reveals functional relationships of sarcomere components in Caenorhabditis elegans. AB - The sarcomere, the fundamental unit of muscle contraction, is a highly-ordered complex of hundreds of proteins. Despite decades of genetics work, the functional relationships and the roles of those sarcomeric proteins in animal behaviors remain unclear. In this paper, we demonstrate that optogenetic activation of the motor neurons that induce muscle contraction can facilitate quantitative studies of muscle kinetics in C. elegans. To increase the throughput of the study, we trapped multiple worms in parallel in a microfluidic device and illuminated for photoactivation of channelrhodopsin-2 to induce contractions in body wall muscles. Using image processing, the change in body size was quantified over time. A total of five parameters including rate constants for contraction and relaxation were extracted from the optogenetic assay as descriptors of sarcomere functions. To potentially relate the genes encoding the sarcomeric proteins functionally, a hierarchical clustering analysis was conducted on the basis of those parameters. Because it assesses physiological output different from conventional assays, this method provides a complement to the phenotypic analysis of C. elegans muscle mutants currently performed in many labs; the clusters may provide new insights and drive new hypotheses for functional relationships among the many sarcomere components. PMID- 26822333 TI - [Changes in mineral and bone disorder management in a French cohort of hemodialysis patients between 2008 and 2012: The National Bone and Mineral Metabolism observatory (Photo-Graphe 2 and 3)]. AB - INTRODUCTION: Chronic kidney disease progressively induces a disorder of mineral and bone metabolism (CKD-MBD) which also leads to cardiovascular abnormalities. Previous studies showed that only few hemodialysis patients had serum calcium, phosphate and parathyroid hormone levels within the K/DOQI (Kidney-Disease Outcomes Quality Initiative) targets of 2003. Our aim was to identify the impact of different therapeutic strategies and that of the KDIGO (Kidney-Disease: Improving Global Outcomes) targets of 2009 on the control of CKD-MBD. PATIENTS AND METHODS: The French calcium and phosphate observatory monitors the mineral metabolism of patients with CKD at the local, regional and national level every six months. We compared the data recorded in June 2008 (n=1914 patients) with those collected in October 2012 (n=2481) for patients aged 18 years or more, who started hemodialysis therapy within the last 12 months. RESULTS: As compared with 2008, in 2012 fewer patients had hyperphosphatemia (55.1 % versus 64.7 %), hypocalcemia (35.5 % versus 40.3 %) and hyperparathyroidism (9.8 % versus 10.1 %) according to the KDIGO guideline, and more had hypophosphatemia (9.6 % versus 6.5 %), hypercalcemia (3.9 % versus 2.2 %) and hypoparathyroidism (31.5 % versus 25.8 %) (P<0.001, P<0.001 and P=0.002 respectively for differences in serum phosphate, calcium and PTH levels). Mean (+/- standard deviation [SD]) serum 25 OH vitamin D levels increased by 1.6-fold, from 48.3+/-42.6 nmol/L in 2008 to 76.6+/-45.8 nmol/L in 2012. Between 2008 and 2012, the prescription of native vitamin D derivatives and sevelamer (HCl or carbonate) increased whereas that of cinacalcet, lanthanum carbonate, calcium-chelating agents and active vitamin D derivatives decreased. CONCLUSION: Despite a slight improvement of biochemical CKD-MBD parameters in the observation period only few patients reached the three KDIGO targets (11.5 % in 2012 versus 11.1 % in 2008). PMID- 26822334 TI - Averting the legacy of kidney disease-Focus on childhood. PMID- 26822335 TI - Measuring perceived ceiling height in a visual comparison task. AB - When judging interior space, a dark ceiling is judged to be lower than a light ceiling. The method of metric judgments (e.g., on a centimetre scale) that has typically been used in such tasks may reflect a genuine perceptual effect or it may reflect a cognitively mediated impression. We employed a height-matching method in which perceived ceiling height had to be matched with an adjustable pillar, thus obtaining psychometric functions that allowed for an estimation of the point of subjective equality (PSE) and the difference limen (DL). The height matching method developed in this paper allows for a direct visual match and does not require metric judgment. It has the added advantage of providing superior precision. Experiment 1 used ceiling heights between 2.90 m and 3.00 m. The PSE proved sensitive to slight changes in perceived ceiling height. The DL was about 3% of the physical ceiling height. Experiment 2 found similar results for lower (2.30 m to 2.50 m) and higher (3.30 m to 3.50 m) ceilings. In Experiment 3, we additionally varied ceiling lightness (light grey vs. dark grey). The height matches showed that the light ceiling appeared significantly higher than the darker ceiling. We therefore attribute the influence of ceiling lightness on perceived ceiling height to a direct perceptual rather than a cognitive effect. PMID- 26822336 TI - Consequences of a male takeover on mating skew in wild Sanje mangabeys. AB - Among primate species living in multimale-multifemale groups, the number of receptive females may determine the rank of the lowest male that copulates (priority of access model, or PoA [Altmann SA. 1962. A field study of the sociobiology of rhesus monkeys, Macaca mulatta. Annals of the New York Academy of Sciences 102:338-435]). Factors, such as temporary instability in the hierarchy and female behavior can, however, affect high-ranking males' ability to monopolize females, reducing mating skew and causing the hierarchy to depart from predictions of PoA. Here, I use behavioral data collected over a 22-month period on a wild group of Sanje mangabeys (Cercocebus sanjei) to examine the effect of a takeover by two immigrating males who became alpha and beta in the hierarchy, and of female behavior on male mating skew. Data on male agonistic interactions were collected on nine males using ad libitum observations, while information on male mating success (i.e., daily proportion of ejaculatory copulations with the focal female) was collected through focal follows of 12 sexually receptive females. Before the takeover, the hierarchy was stable and highly skewed, with the alpha male monopolizing up to 75% of copulations. At this time, however, mating skew did not follow the predictions of PoA. During the takeover, from the time one of the newly immigrant males replaced the alpha until the second immigrant male became the new beta, the stability of the hierarchy dropped significantly and mating was no longer skewed. Accordingly, the top two ranking males at that time (i.e., the new alpha and former beta) accounted for only 33% of copulations. After the takeover, rank stability increased, and mating skew followed the PoA. Female mating solicitations also had a significant positive effect on male mating success, and may have contributed to the deviation from the PoA. This study demonstrates that temporary rank instability decreases high-ranking males' ability to monopolize copulations, causing a departure from the predictions of the PoA. Am. J. Primatol. 79:e22532, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26822337 TI - A Facile and Low-Cost Method to Enhance the Internal Quantum Yield and External Light-Extraction Efficiency for Flexible Light-Emitting Carbon-Dot Films. AB - Solution-processed, non-toxic carbon dots (CDs) have attracted much attention due to their unique photoluminescence (PL) properties. They are promising emissive layers for flexible light-emitting devices. To this end, the CDs in pristine aqueous solutions need to be transferred to form solid-state thin films without sacrificing their original PL characteristics. Unfortunately, solid-state PL quenching induced by extra non-radiative (NR) energy transfer among CDs would significantly hinder their practical applications in optoelectronics. Here, a facile, low-cost and effective method has been utilized to fabricate high performance CD/polymer light-emitting flexible films with submicron-structured patterns. The patterned polymers can serve as a solid matrix to disperse and passivate CDs, thus achieving high internal quantum yields of 61%. In addition, they can act as an out-coupler to mitigate the waveguide-mode losses, approximately doubling the external light-extraction efficiency. Such CD/polymer composites also exhibit good photo-stability, and thus can be used as eco friendly, low-cost phosphors for solid-state lighting. PMID- 26822338 TI - Sustained presentation of BMP-2 enhances osteogenic differentiation of human adipose-derived stem cells in gelatin hydrogels. AB - Human adipose-derived stem cells (hASCs) show great potential for healing bone defects. Bone morphogenetic protein-2 (BMP-2) has been reported to stimulate their osteogenic differentiation both in vitro and in vivo. Here, methacrylated gelatin (GelMA) hydrogels were evaluated as a system to deliver BMP-2 to encapsulated hASCs from two different donors, and BMP-2 delivered from the hydrogels was compared to BMP-2 presented exogenously in culture media. GelMA hydrogels were shown to provide sustained, localized presentation of BMP-2 due to electrostatic interactions between the growth factor and biomaterial after an initial burst release. Both donors exhibited similar responses to the loaded and exogenous growth factor; BMP-2 from the hydrogels had a statistically significant effect on hASC osteogenic differentiation compared to exogenous BMP-2. Expression of alkaline phosphatase was accelerated, and cells in hydrogels with loaded BMP-2 deposited more calcium at one, two, and four weeks than cells without BMP-2 or with the growth factor presented in the media. There were no statistically significant differences in calcium content between groups with 25, 50, or 100 ug/mL loaded BMP-2, suggesting that using a lower growth factor dose may be as effective as a higher loading amount in this system. Taken together, these findings suggest that controlled delivery of BMP-2 from the GelMA enhances its osteogenic bioactivity compared to free growth factor presented in the media. Thus, the GelMA system is a promising biomaterial for BMP-2-mediated hASC osteogenesis. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1387-1397, 2016. PMID- 26822339 TI - Fertility and Cancer Treatment. PMID- 26822340 TI - Helicobacter pylori and Antibiotic Resistance, A Continuing and Intractable Problem. AB - Helicobacter pylori, a human pathogen with a high global prevalence, is the causative pathogen for multiple gastrointestinal diseases, especially chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric malignancies. Antibiotic therapies remain the mainstay for H. pylori eradication; however, this strategy is hampered by the emergence and spread of H. pylori antibiotic resistance. Exploring the mechanistic basis of this resistance is becoming one of the major research questions in contemporary biomedical research, as such knowledge could be exploited to devise novel rational avenues for counteracting the existing resistance and devising strategies to avoid the development of a novel anti-H. pylori medication. Encouragingly, important progress in this field has been made recently. Here, we attempt to review the current state and progress with respect to the molecular mechanism of antibiotic resistance for H. pylori. A picture is emerging in which mutations of various genes in H. pylori, resulting in decreased membrane permeability, altered oxidation-reduction potential, and a more efficient efflux pump system. The increased knowledge on these mechanisms produces hope that antibiotic resistance in H. pylori can ultimately be countered. PMID- 26822341 TI - Expression of the inactive ZmMEK1 induces salicylic acid accumulation and salicylic acid-dependent leaf senescence. AB - Leaf senescence is the final leaf developmental process that is regulated by both intracellular factors and environmental conditions. The mitogen-activated protein kinase (MAPK) signaling cascades have been shown to play important roles in regulating leaf senescence; however, the component(s) downstream of the MAPK cascades in regulating leaf senescence are not fully understood. Here we showed that the transcriptions of ZmMEK1, ZmSIMK1, and ZmMPK3 were induced during dark induced maize leaf senescence. Furthermore, in-gel kinase analysis revealed the 42 kDa MAPK was activated. ZmMEK1 interacted with ZmSIMK1 in yeast and maize mesophyll protoplasts and ZmSIMK1 was activated by ZmMEK1 in vitro. Expression of a dominant negative mutant of ZmMEK1 in Arabidopsis transgenic plants induced salicylic acid (SA) accumulation and SA-dependent leaf senescence. ZmMEK1 interacted with Arabidopsis MPK4 in yeast and activated MPK4 in vitro. SA treatment accelerated dark-induced maize leaf senescence. Moreover, blockage of MAPK signaling increased endogenous SA accumulation in maize leaves. These findings suggest that ZmMEK1-ZmSIMK1 cascade and its modulating SA levels play important roles in regulating leaf senescence. PMID- 26822342 TI - Histopathological and Biochemical Effects of Ecballium elaterium on Sepsis Induced Lung Injury. AB - PURPOSE: The aim of this study was to investigate the role of Ecballium elaterium (EE) on sepsis-induced lung injury. MATERIALS AND METHODS: A total of 30 male rats were divided into three groups as follows: control, sepsis, and treatment groups (sepsis + EE) with each group containing 10 rats. A rat model of sepsis induced by cecal ligation and puncture (CLP) was used. In the treatment group, rats were injected intraperitoneally with 2.5 mg/kg EE after CLP. Interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) values after a 24-hr period were measured via cardiac puncture. Animals were harvested after the procedure and biochemical analysis was done and histopathological changes of the tissue sections of lungs were examined thereafter. RESULTS: A statistically significant decrease was observed in the IL-6 (p < .05), TNF-alpha (p < .05), and TOS (p < .01) levels in the sera of the treatment group compared to those of the sepsis group. Following the treatment, the TOS (p = .01) and OSI (p < .05) levels in the lung tissue of rats indicated a statistically significant decrease compared to those of the sepsis group. The histopathological follow-up undertaken after the administration of the EE treatment to septic rats showed significantly lower values of alveolar wall thickness (p < .001), interstitial edema (p = .018), and neutrophil infiltration (p = .047). CONCLUSION: EE treatment may have beneficial effects on sepsis-induced lung injury, and therefore has potential for clinical use. PMID- 26822343 TI - Role of PI3K/Akt signal pathway on proliferation of mesangial cell induced by HMGB1. AB - Mesangial cell (MC) proliferation is an important event in LN. Our previous studies have shown that extracellular High Mobility Group Box-1 protein (HMGB1) plays a critical role in pathophysiological mechanism of lupus nephritis (LN) and HMGB1 could induce MC proliferation. The purpose of this study is to investigate the effect of phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt) signal pathway activation on mesangial cell proliferation induced by HMGB1 and whether Toll-like receptor 2 (TLR2) plays an important role in this progress. The results showed that HMGB1 induced overexpression of p85, p110 and p-Akt in mouse mesangial cell (MMC) and increased the proliferative level of MMC cells. In addition, HMGB1 induced a physical interaction between TLR2 and p85. The TLR2 neutralization antibody and LY294002 both reduced the MMC proliferation levels induced by HMGB1 and also blocked the HMGB1-dependent phosphorylation of the Akt. Thus, HMGB1 increases interaction between TLR2 with p85 and in sequence phosphorylates Akt at ser473, thereafter mediates MMC proliferation, which contributed significantly to the pathophysiology of MMCs dysfunction. PMID- 26822344 TI - Recent advances in mass spectrometry analysis of histone post-translational modifications: potential clinical impact of the PAT-H-MS approach. AB - Histone post-translational modifications (hPTMs) contribute to the regulation of gene expression and increasing evidence links them to the development of various pathologies, highlighting their potential as biomarkers for prognostic, diagnostic and therapeutic applications. Mass spectrometry (MS) has emerged as a powerful analytical tool for hPTM analysis, which has also been applied to the analysis of epigenetic aberrations in diseases. However, the potential offered by the MS-based hPTM analysis of clinical samples for epigenetic biomarker discovery has been left largely unexploited. This article summarizes the contribution of MS based approaches to clinical epigenetics, with a special focus on the PAThology tissue analysis of Histones by Mass Spectrometry (PAT-H-MS) approach--which represents the first application of MS-based hPTM analysis to formalin-fixed paraffin-embedded clinical samples--discussing its strengths and limitations, as well as possible implementations. PMID- 26822345 TI - Development and Validation of Elective and Nonelective Risk Prediction Models for In-Hospital Mortality in Proximal Aortic Surgery Using the National Institute for Cardiovascular Outcomes Research (NICOR) Database. AB - BACKGROUND: To facilitate patient choice and the risk adjustment of consultant outcomes in aortic operations, reliable predictive tools are required. Our objective was to develop a risk prediction model for in-hospital mortality after operation on the proximal aorta. METHODS: Data for 8641 consecutive UK patients undergoing proximal aortic operation from the National Institute for Cardiovascular Outcomes Research database from April 2007 to March 2013 were analyzed. Multivariable logistic regression was used to identify independent predictors of in-hospital mortality. Model calibration and discrimination were assessed. RESULTS: In-hospital mortality was 4.6% in elective operations and 16.5% in nonelective operations. In the elective model, previous cardiac operation (adjusted odds ratio [OR] 4.1, 95% confidence interval [CI]: 3.0 to 4.7) and ejection fraction greater than 30% (adjusted OR 2.3, 95% CI: 1.7 to 3.1) were the strongest predictors of mortality (p < 0.001). The area under the receiver operating characteristic (AUROC) curve was 0.805 (95% CI: 0.802 to 0.807) with a bias-corrected value of 0.795. Model calibration was acceptable (p = 0.427) on the basis of the Hosmer-Lemeshow goodness-of-fit test. In the nonelective model, salvage operations (adjusted OR 9.9, 95% CI: 6.5 to 15.2) and previous cardiac operation (adjusted OF 3.9, 95% CI: 3.0 to 5.0) were the strongest predictors of mortality (p < 0.001). The AUROC curve was 0.761 (95% CI: 0.761 to 0.765) with a bias-corrected value of 0.756, and model calibration was also found to be acceptable (p = 0.616). CONCLUSIONS: We propose the use of these risk models to improve patient choice and to enhance patients' awareness of risks and risk-adjust aortic operation outcomes for case-mix. PMID- 26822347 TI - Myocardial Revascularization Exclusively With Bilateral Internal Thoracic Arteries in T-Graft Configuration: Effects on Late Survival. AB - BACKGROUND: We studied long-term survival using bilateral internal thoracic artery (BITA) grafting in a T-configuration exclusively versus using single internal thoracic artery (SITA) grafting in patients with multivessel disease. METHODS: Consecutive coronary operations performed at a single center between 1996 and 2014 were reviewed. Long-term survival among patients receiving coronary revascularization exclusively with BITA grafting in a T-configuration (n = 2,098) versus SITA grafts plus other types of conduits (saphenous vein graft [SVG] and radial artery [RA]) grafts (n = 1,659). In patients who underwent BITA grafting, the left internal thoracic artery (LITA) was grafted mainly to the left anterior descending artery, whereas the right internal thoracic artery (RITA) was used more commonly to graft the circumflex (Cx) artery and the right coronary system as T-grafts. A total of 485 pairs of patients were matched using propensity scores. Cox proportional hazard models were generated to examine the association of arterial BITA grafting with mortality. RESULTS: Patients in the BITA group were more likely to be younger (BITA, 63.7 +/- 9.1 versus SITA, 65.0 +/- 9.9; p < 0.0001). At 30 days, patients who underwent BITA grafting experienced reduced unadjusted mortality (BITA, 1.2% versus SITA, 4.4%; p < 0.0001). At 10 years, patients who underwent BITA grafting experienced superior unadjusted survival (BITA, 82.6% +/- 1.8% versus SITA, 76.1% +/- 1.3%; p = 0.001). Cox regression analysis in the entire study cohort showed that BITA grafting was associated with improved survival (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.58 0.87; p < 0.001). In the propensity-score-adjusted analysis, patients who underwent BITA grafting had similar in-hospital mortality (BITA, 1.6% versus SITA, 2.9%; p = 0.196). Patients who underwent BITA grafting still showed improved survival at 10 years (BITA, 81.0% +/- 4.1% versus SITA, 71.8% +/- 2.5%; p = 0.039). CONCLUSIONS: This study suggests that coronary artery operations exclusively with BITA grafting in a T-configuration may be associated with better long-term survival than grafting with SITA plus other types of conduits. PMID- 26822348 TI - Diagnostic Performance of (18)F-Fluorodeoxyglucose in 162 Small Pulmonary Nodules Incidentally Detected in Subjects Without a History of Malignancy. AB - BACKGROUND: Solitary pulmonary nodule (SPN) still represents a diagnostic challenge. The aim of our study was to evaluate the diagnostic performance of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography in one of the largest samples of small SPNs, incidentally detected in subjects without a history of malignancy (nonscreening population) and undetermined at computed tomography. METHODS: One-hundred and sixty-two small (>0.8 to 1.5 cm) and, for comparison, 206 large nodules (>1.5 to 3 cm) were retrospectively evaluated. Diagnostic performance of (18)F-fluorodeoxyglucose visual analysis, receiver operating characteristic (ROC) analysis for maximum standardized uptake value (SUVmax), and Bayesian analysis were assessed using histology or radiological follow-up as a golden standard. RESULTS: In 162 small nodules, (18)F fluorodeoxyglucose visual and ROC analyses (SUVmax = 1.3) provided 72.6% and 77.4% sensitivity and 88.0% and 82.0% specificity, respectively. The prevalence of malignancy was 38%; Bayesian analysis provided 78.8% positive and 16.0% negative posttest probabilities of malignancy. In 206 large nodules (18)F fluorodeoxyglucose visual and ROC analyses (SUVmax = 1.9) provided 89.5% and 85.1% sensitivity and 70.8% and 79.2% specificity, respectively. The prevalence of malignancy was 65%; Bayesian analysis provided 85.0% positive and 21.6% negative posttest probabilities of malignancy. In both groups, malignant nodules had a significant higher SUVmax (p < 0.0001) than benign nodules. Only in the small group, malignant nodules were significantly larger (p = 0.0054) than benign ones. CONCLUSIONS: (18)F-fluorodeoxyglucose can be clinically relevant to rule in and rule out malignancy in undetermined small SPNs, incidentally detected in nonscreening population with intermediate pretest probability of malignancy, as well as in larger ones. Visual analysis can be considered an optimal diagnostic criterion, adequately detecting a wide range of malignant nodules with different metabolic activity. PMID- 26822346 TI - Use and Outcomes of Minimally Invasive Lobectomy for Stage I Non-Small Cell Lung Cancer in the National Cancer Data Base. AB - BACKGROUND: Previous studies have raised concerns that video-assisted thoracoscopic (VATS) lobectomy may compromise nodal evaluation. The advantages or limitations of robotic lobectomy have not been thoroughly evaluated. METHODS: Perioperative outcomes and survival of patients who underwent open versus minimally-invasive surgery (MIS [VATS and robotic]) lobectomy and VATS versus robotic lobectomy for clinical T1-2, N0 non-small cell lung cancer from 2010 to 2012 in the National Cancer Data Base were evaluated using propensity score matching. RESULTS: Of 30,040 lobectomies, 7,824 were VATS and 2,025 were robotic. After propensity score matching, when compared with the open approach (n = 9,390), MIS (n = 9,390) was found to have increased 30-day readmission rates (5% versus 4%, p < 0.01), shorter median hospital length of stay (5 versus 6 days, p < 0.01), and improved 2-year survival (87% versus 86%, p = 0.04). There were no significant differences in nodal upstaging and 30-day mortality between the two groups. After propensity score matching, when compared with the robotic group (n = 1,938), VATS (n = 1,938) was not significantly different from robotics with regard to nodal upstaging, 30-day mortality, and 2-year survival. CONCLUSIONS: In this population-based analysis, MIS (VATS and robotic) lobectomy was used in the minority of patients for stage I non-small cell lung cancer. MIS lobectomy was associated with shorter length of hospital stay and was not associated with increased perioperative mortality, compromised nodal evaluation, or reduced short term survival when compared with the open approach. These results suggest the need for broader implementation of MIS techniques. PMID- 26822349 TI - Bias and precision analysis of diffusional kurtosis imaging for different acquisition schemes. AB - PURPOSE: Diffusional kurtosis imaging (DKI) is an approach to characterizing the non-Gaussian fraction of water diffusion in biological tissue. However, DKI is highly susceptible to the low signal-to-noise ratio of diffusion-weighted images, causing low precision and a significant bias due to Rician noise distribution. Here, we evaluate precision and bias using weighted linear least squares fitting of different acquisition schemes including several multishell schemes, a diffusion spectrum imaging (DSI) scheme, as well as a compressed sensing reconstruction of undersampled DSI scheme. METHODS: Monte Carlo simulations were performed to study the three-dimensional distribution of the apparent kurtosis coefficient (AKC). Experimental data were acquired from one healthy volunteer with multiple repetitions, using the same acquisition schemes as for the simulations. RESULTS: The angular distribution of the bias and precision were very inhomogeneous. While axial kurtosis was significantly overestimated, radial kurtosis was underestimated. The precision of radial kurtosis was up to 10-fold lower than axial kurtosis. CONCLUSION: The noise bias behavior of DKI is highly complex and can cause overestimation as well as underestimation of the AKC even within one voxel. The acquisition scheme with three shells, suggested by Poot et al, provided overall the best performance. Magn Reson Med 76:1684-1696, 2016. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26822350 TI - Do socio-economic inequalities in infant growth in rural India operate through maternal size and birth weight? AB - BACKGROUND: In total, 3.1 million young children die every year from under nutrition. Greater understanding of associations between socio-economic status (SES) and the biological factors that shape under-nutrition are required to target interventions. AIM: To establish whether SES inequalities in under nutrition, proxied by infant size at 12 months, operate through maternal and early infant size measures. SUBJECTS AND METHODS: The sample comprised 347 Indian infants born in 60 villages in rural Andhra Pradesh 2005-2007. Structural equation path models were applied to decompose the total relationship between SES (standard of living index) and length and weight for age Z-scores (LAZ/WAZ) at 12 months into direct and indirect (operating through maternal BMI and height, birthweight Z-score and LAZ/WAZ at 6 months) paths. RESULTS: SES had a direct positive association with LAZ (Standardised coefficient = 0.08, 95% CI = 0.02 0.13) and WAZ at age 12 months (Standardised coefficient = 0.08, 95% CI = 0.02 0.15). It also had additional indirect positive associations through increased maternal height and subsequently increased birthweight and WAZ/LAZ at 6 months, accounting for 35% and 53% of the total effect for WAZ and LAZ, respectively. CONCLUSION: Findings support targeting evidence based growth interventions towards infants from the poorest families with the shortest mothers. Increasing SES can improve growth for two generations. PMID- 26822351 TI - Animal models for addiction medicine: From vulnerable phenotypes to addicted individuals. AB - This chapter highlights the use of several animal models of abuse liability. The overall goal is to describe the most frequently used methods, unconditioned behaviors and conditioned behaviors, and how investigators can use these techniques to compare drugs and to understand the mechanisms of action mediating abuse liability. Thus, for each type of animal model described, research will be highlighted on three general features related to the use of the model: (1) determine abuse potential, (2) treatment efficacy, and (3) brain-related changes associated with drug administration. PMID- 26822352 TI - Animal models of drug relapse and craving: From drug priming-induced reinstatement to incubation of craving after voluntary abstinence. AB - High rates of relapse to drug use during abstinence is a defining feature of drug addiction. In abstinent drug users, drug relapse is often precipitated by acute exposure to the self-administered drug, drug-associated cues, stress, as well as by short-term and protracted withdrawal symptoms. In this review, we discuss different animal models that have been used to study behavioral and neuropharmacological mechanisms of these relapse-related phenomena. In the first part, we discuss relapse models in which abstinence is achieved through extinction training, including the established reinstatement model, as well as the reacquisition and resurgence models. In the second part, we discuss recent animal models in which drug relapse is assessed after either forced abstinence (e.g., the incubation of drug craving model) or voluntary (self-imposed) abstinence achieved either by introducing adverse consequences to ongoing drug self-administration (e.g., punishment) or by an alternative nondrug reward using a discrete choice (drug vs. palatable food) procedure. We conclude by briefly discussing the potential implications of the recent developments of animal models of drug relapse after voluntary abstinence to the development of medications for relapse prevention. PMID- 26822353 TI - Computational modeling for addiction medicine: From cognitive models to clinical applications. AB - Decision-making tasks that have good ecological validity, such as simulated gambling tasks, are complex, and performance on these tasks represents a synthesis of several different underlying psychological processes, such as learning from experience, and motivational processes such as sensitivity to reward and punishment. Cognitive models can be used to break down performance on these tasks into constituent processes, which can then be assessed and studied in relation to clinical characteristics and neuroimaging outcomes. Whether it will be possible to improve treatment success by targeting these constituent processes more directly remains unexplored. We review the development and testing of the Expectancy-Valence and Prospect-Valence Learning models from the past 10 years or so using simulated gambling tasks, in particular the Iowa and Soochow Gambling Tasks. We highlight the issues of model generalizability and parameter consistency, and we describe findings obtained from these models in clinical populations including substance use disorders. We then suggest future directions for this research that will help to bring its utility to broader research and clinical applications. PMID- 26822354 TI - Electrophysiology for addiction medicine: From methodology to conceptualization of reward deficits. AB - In the past decade, electroencephalographic research on addiction has employed passive viewing, oddball, inhibition, prediction, gambling, and reversal learning tasks to study how substance users neurally prioritize drug-related rewards at the expense of nondrug rewards. On the whole, findings across substances (alcohol, cannabis, cocaine, nicotine, opiates, gambling, and gaming) demonstrate impairments in the differentiation of monetary incentives and the inhibition of prepotent responses. Furthermore, exaggerated resources devoted to drug cues and attenuated processing of other types of pleasant emotional stimuli predict greater probability of future drug use. However, drug use recency, frequency, sensitivity, and insight all appear to be moderators of these effects. We argue that more longitudinal studies are warranted to determine the time course of reward processing as a function of development and chronicity. PMID- 26822355 TI - Neurocognitive rehabilitation for addiction medicine: From neurophysiological markers to cognitive rehabilitation and relapse prevention. AB - Currently, relapse prevention remains the main challenge in addiction medicine, indicating that the established treatment methods combining psychotherapy with neuropharmacological interventions are not entirely effective. Therefore, there is a push to develop alternatives to psychotherapy- and medication-based approaches to addiction treatment. Two major cognitive factors have been identified that trigger relapse in addicted patients: attentional biases directed toward drug-related cues, which increase the urge to consume, and impaired response inhibition toward these cues, which makes it more difficult for addicted people to resist temptation. Recent studies on newly detoxified alcoholic patients have shown that by using the appropriate tasks to index these cognitive functions with event-related potentials (ERPs), it is possible to discriminate between future relapsers and nonrelapsers. These preliminary data suggest that the ERP technique has great clinical potential for preventing relapse in alcohol dependent patients, as well as for addictive states in general. Indeed, ERPs may help to identify patients highly vulnerable to relapse and allow the development of individually adapted cognitive rehabilitation programs. The implementation of this combined approach requires an intense collaboration between psychiatry departments, clinical neurophysiology laboratories, and neuropsychological rehabilitation centers. The potential pitfalls and limitations of this approach are also discussed. PMID- 26822357 TI - Functional neuroimaging for addiction medicine: From mechanisms to practical considerations. AB - During last 20 years, neuroimaging with functional magnetic resonance imaging (fMRI) in people with drug addictions has introduced a wide range of quantitative biomarkers from brain's regional or network level activities during different cognitive functions. These quantitative biomarkers could be potentially used for assessment, planning, prediction, and monitoring for "addiction medicine" during screening, acute intoxication, admission to a program, completion of an acute program, admission to a long-term program, and postgraduation follow-up. In this chapter, we have briefly reviewed main neurocognitive targets for fMRI studies associated with addictive behaviors, main study types using fMRI among drug dependents, and potential applications for fMRI in addiction medicine. Main challenges and limitations for extending fMRI studies and evidences aiming at clinical applications in addiction medicine are also discussed. There is still a significant gap between available evidences from group-based fMRI studies and personalized decisions during daily practices in addiction medicine. It will be important to fill this gap with large-scale clinical trials and longitudinal studies using fMRI measures with a well-defined strategic plan for the future. PMID- 26822358 TI - Resting state functional connectivity analysis for addiction medicine: From individual loci to complex networks. AB - Resting state functional connectivity (rsFC) has provided a new and valuable tool for investigating network-level dysfunction in addiction. Following the recent development of a framework of large scale network disruptions, we have been able to arrive at unique insights into craving-related aspects of addiction using rsFC. However, such network-level advancement has thus far eluded our understanding of mesocorticolimbic involvement in addiction. Given the importance of this system in vulnerability and resilience to addiction, understanding mesocorticolimbic dynamics to the same extent could provide critical insights into the disease. To this end, we review here recent studies on addiction that employ rsfC and suggest a new approach, one that combines a novel model for addiction with new experimental techniques as well as participant groups, to accelerate progress in this arena. PMID- 26822356 TI - Structural imaging for addiction medicine: From neurostructure to neuroplasticity. AB - Quantitative morphometry and diffusion tensor imaging have provided new insights into structural brain changes associated with drugs of abuse. In this chapter, we review recent studies using these methods to investigate structural brain abnormalities associated with excessive use of marijuana, stimulants, and opiates. Although many brain regions have been associated with structural abnormalities following abuse of these drugs, brain systems underlying inhibition, mood regulation, and reward are particularly involved. Candidate pathological mechanisms underlying these structural abnormalities include the direct toxic effects of the drugs, neuroinflammation, ischemia, hemorrhage, and abnormal brain development. Returning damaged brain areas to neural health would involve enhancing neuroplasticity. Behavioral, environmental, pharmacological, and cell-based therapies have been correlated with enhanced neuroplasticity following brain injury, providing a basis for new treatments of brain changes associated with excessive drug use. When testing new treatments, structural imaging may prove useful in selecting patients, monitoring recovery, and perhaps, tailoring interventions. PMID- 26822359 TI - PET imaging for addiction medicine: From neural mechanisms to clinical considerations. AB - Positron emission tomography (PET) has been shown to be an effective imaging technique to study neurometabolic and neurochemical processes involved in addiction. That is, PET has been used to research neurobiological differences in substance abusers versus healthy controls and the pharmacokinetics and pharmacodynamics of abused drugs. Over the past years, the research scope has shifted to investigating neurobiological effects of abstinence and treatment, and their predictive power for relapse and other clinical outcomes. This chapter provides an overview of PET methodology, recent human PET studies on drug addiction and their implications for clinical treatment. PMID- 26822361 TI - Human pharmacology for addiction medicine: From evidence to clinical recommendations. AB - Substance use disorders (SUD) are complex and often chronic diseases with negative health outcomes and social consequences. Pharmacological treatment options for SUD can be separated in medications for (i) intoxication, (ii) withdrawal, and (iii) reduction of use together with relapse prevention. This chapter will focus on approved or clinically established pharmacological strategies suited to manage symptoms of withdrawal, and to reduce substance use or to promote abstinence. Hereby SUD involving alcohol, nicotine, stimulants, and opioids are primarily discussed as these substances are considered most harmful for both the individual and the society. Moreover, the pharmacotherapy of SUD related to the use of cannabis, benzodiazepines, and gamma-hydroxybutyrate is also briefly reviewed. Since most approved pharmacological treatment options show only moderate effect sizes especially in the long term, the development of new treatment strategies including new drugs, new combinations of available compounds, and biomarkers for response prediction is still warranted. PMID- 26822360 TI - Genetic imaging consortium for addiction medicine: From neuroimaging to genes. AB - Since the sample size of a typical neuroimaging study lacks sufficient statistical power to explore unknown genomic associations with brain phenotypes, several international genetic imaging consortia have been organized in recent years to pool data across sites. The challenges and achievements of these consortia are considered here with the goal of leveraging these resources to study addiction. The authors of this review have joined together to form an Addiction working group within the framework of the ENIGMA project, a meta analytic approach to multisite genetic imaging data. Collectively, the Addiction working group possesses neuroimaging and genomic data obtained from over 10,000 subjects. The deadline for contributing data to the first round of analyses occurred at the beginning of May 2015. The studies performed on this data should significantly impact our understanding of the genetic and neurobiological basis of addiction. PMID- 26822364 TI - Adolescent psychotherapy for addiction medicine: From brain development to neurocognitive treatment mechanisms. AB - Effectively treating addiction is a challenge among any population, and treatment for adolescents may be particularly challenging in the context of ongoing neurodevelopment, which may alter the brain's initial response to substances as well as its response to treatment. One way to improve treatment outcomes for youth is to use a translational perspective that explicitly connects cognitive and neurodevelopmental fields with the field of behavioral therapies. This integrative approach is a potential first step to inform the correspondence between the neurocognitive and behavioral fields in youth addiction. This chapter seeks to provide context for neurocognitive treatment studies by first discussing recent structural and functional neuroimaging studies showing associations with substance use or behavioral addictions. Several regions of interest are then proposed that appear to also be associated with addiction treatment across multiple studies, namely, the accumbens/striatum, precuneus, insula, anterior cingulate cortex, and dorsolateral prefrontal cortex. This research suggests that reward, self-reflective, and executive control areas might be especially relevant in youth behavioral treatment response, and preliminary evidence suggests that existing treatments may encourage neurocognitive changes in these areas. PMID- 26822363 TI - Cognitive interventions for addiction medicine: Understanding the underlying neurobiological mechanisms. AB - Neuroimaging provides a tool for investigating the neurobiological mechanisms of cognitive interventions in addiction. The aim of this review was to describe the brain circuits that are recruited during cognitive interventions, examining differences between various treatment modalities while highlighting core mechanisms, in drug addicted individuals. Based on a systematic Medline search we reviewed neuroimaging studies on cognitive behavioral therapy, cognitive inhibition of craving, motivational interventions, emotion regulation, mindfulness, and neurofeedback training in addiction. Across intervention modalities, common results included the normalization of aberrant activity in the brain's reward circuitry, and the recruitment and strengthening of the brain's inhibitory control network. Results suggest that different cognitive interventions act, at least partly, through recruitment of a common inhibitory control network as a core mechanism. This implies potential transfer effects between training modalities. Overall, results confirm that chronically hypoactive prefrontal regions implicated in cognitive control in addiction can be normalized through cognitive means. PMID- 26822365 TI - Cognitive neuroscience of cognitive retraining for addiction medicine: From mediating mechanisms to questions of efficacy. AB - Cognitive retraining or cognitive bias modification (CBM) involves having subjects repeatedly perform a computerized task designed to reduce the impact of automatic processes that lead to harmful behavior. We first discuss the theory underlying CBM and provide a brief overview of important research progress in its application to addiction. We then focus on cognitive- and neural-mediating mechanisms. We consider recent criticism of both CBM and its theoretical foundations. Evaluations of CBM could benefit from considering theory-driven factors that may determine variations in efficacy, such as motivation. Concerning theory, while there is certainly room for fundamental advances in current models, we argue that the basic view of impulsive behavior and its control remains a useful and productive heuristic. Finally, we briefly discuss some interesting new directions for CBM research: enhancement of training via transcranial direct current stimulation, online training, and gamification, i.e., the use of gameplay elements to increase motivation. PMID- 26822366 TI - Perspectives on neurocognitive rehabilitation as an adjunct treatment for addictive disorders: From cognitive improvement to relapse prevention. AB - Addiction, as a brain disorder, can be defined with two distinct but interacting components: drug dependency and neurocognitive deficits. Most of the therapeutic interventions in addiction medicine, including pharmacological or psychosocial therapies, that are in clinical use have been mainly focused on directly addressing addictive behaviors, especially drug use and urges to use drugs. In the field of addiction treatment, it is often presumed that drug users' neurocognitive deficits will reverse following abstinence. However, in many cases, neurocognitive deficits are not fully ameliorated following sustained abstinence, and neurocognitive function may further deteriorate in early abstinence. It can be argued that many cognitive functions, such as sustained attention and executive control, are essential for full recovery and long-term abstinence from addiction. Recent advances in cognitive neuroscience have provided scientific foundations for neurocognitive rehabilitation as a means of facilitating recovery from drug addiction. Neurocognitive rehabilitation for drug addicted individuals could be implemented as part of addiction treatment, with highly flexible delivery methods including traditional "paper and pencil" testing, or computer-based technology via laptops, web-based, or smartphones in inpatient and outpatient settings. Despite this promise, there has been limited research into the potential efficacy of neurocognitive rehabilitation as a treatment for drug addiction. Further, many questions including the optimum treatment length, session duration, and necessary treatment adherence for treatment efficacy remain to be addressed. In this chapter, we first introduce cognitive rehabilitation as one of the potential areas to bridge the gap between cognitive neuroscience and addiction medicine, followed by an overview of current challenges and future directions. PMID- 26822367 TI - Noninvasive brain stimulation for addiction medicine: From monitoring to modulation. AB - Addiction is a chronic relapsing brain disease with significant economical and medical burden on the societies but with limited effectiveness in the available treatment options. Better understanding of the chemical, neuronal, regional, and network alterations of the brain due to drug abuse can ultimately lead to tailoring individualized and more effective interventions. To this end, employing new assessment and intervention procedures seems crucial. Noninvasive brain stimulation (NIBS) techniques including transcranial electrical and magnetic stimulations (tES and TMS) have provided promising opportunities for the addiction medicine in two main domains: (1) providing new insights into neurochemical and neural circuit changes in the human brain cortex and (2) understanding the role of different brain regions by using NIBS and modulating cognitive functions, such as drug craving, risky decision making, inhibitory control and executive functions to obtain specific treatment outcomes. In spite of preliminary positive results, there are several open questions, which need to be addressed before routine clinical utilization of NIBS techniques in addiction to medicine, such as how to account for interindividual differences, define optimal cognitive and neural targets, optimize stimulation protocols, and integrate NIBS with other therapeutic methods. Therefore, in this chapter we revise the available literature on the use of NIBS (TMS and tES) in the diagnostic, prognostic, and therapeutic aspects of the addiction medicine. PMID- 26822362 TI - Emerging targets for addiction neuropharmacology: From mechanisms to therapeutics. AB - Drug abuse represents a considerable burden of disease and has enormous economic impacts on societies. Over the years, few medications have been developed for clinical use. Their utilization is endowed with several limitations, including partial efficacy or significant side effects. On the other hand, the successful advancement of these compounds provides an important proof of concept for the feasibility of drug development programs in addiction. In recent years, a wealth of information has been generated on the psychological mechanisms, genetic or epigenetic predisposing factors, and neurobiological adaptations induced by drug consumption that interact with each other to contribute to disease progression. It is now clear that addiction develops through phases, from initial recreational use to excessive consumption and compulsive drug seeking, with a shift from positive to negative reinforcement driving motivated behaviors. A greater understanding of these mechanisms has opened new vistas in drug development programs. Researchers' attention has been shifted from investigation of classical targets associated with reward to biological substrates responsible for negative reinforcement, impulse loss of control, and maladaptive mechanisms resulting from protracted drug use. From this research, several new biological targets for the development of innovative therapies have started to emerge. This chapter offers an overview of targets currently under scrutiny for the development of new medications for addiction. This work is not exhaustive but rather it provides a few examples of how this research has advanced in recent years by virtue of studies carried out in our laboratory. PMID- 26822368 TI - What the alcohol doctor ordered from the neuroscientist: Theragnostic biomarkers for personalized treatments. AB - Major advances in the neuroscientific understanding of alcohol actions have so far not translated into measurably improved clinical outcomes in alcoholism. Future treatment development should be guided by accumulating insights into a diverse range of biological mechanisms that maintain the pathophysiology of alcoholism in different individuals, but also at different points in time within any given patient. This biological diversity calls for the development and use of biological markers predictive of treatment response in the individual case, at the specific stage of the disease, here called "theragnostics." As novel therapeutic mechanisms and molecules targeting these mechanisms are discovered, the use of theragnostics will be critical for their successful clinical development, as well as their optimal subsequent clinical use. During clinical development, lest theragnostics are utilized, efficacy signals will risk remaining undetected when diluted in study populations that are not appropriately selected. Similarly, for treatments that reach approval, clinical acceptance, and optimal use will require the proper identification of responsive patients. Here, we discuss desirable properties of theragnostic biomarkers in alcohol addiction using two examples: alcohol-induced activation of brain reward circuitry as assessed using positron emission tomography of functional magnetic resonance imaging; and central glutamate tone, as assessed using MR spectroscopy. PMID- 26822369 TI - What does addiction medicine expect from neuroscience? From genes and neurons to treatment responses. AB - The field of neuroscience is rapidly growing as evidenced by the mapping of the human genome, the progress in brain imaging technologies, and the refinement of sophisticated molecular tools that can be combined with innovative preclinical models. With these advances, it seems that our understanding of processes underlying addiction has never been so great. In comparison, the clinical domain has evolved at a much slower pace. Nonetheless, the addiction medical field has seen some gradual improvements in clinical care with the availability of a larger range of pharmacological options. Notably, several therapeutic alternatives are now offered for the treatment of nicotine, alcohol, and opioid use disorders. Some of these developments in treatment regimens have directly emerged from basic neuroscience research and represent a success story for the bench to beside translational approach. However, the clinical and research needs in addiction medicine are huge. There are still no pharmacological interventions available for psychostimulant and cannabis use disorders. Further, major questions remain unanswered: Would a better understanding of the neurocircuitry of addiction lead to therapeutic intervention? Would a better understanding of the neurochemical signature of addiction lead to the validation of a therapeutic target? Will pharmacogenetics hold its promise as a personalized medicine treatment approach? Using recent research developments, we will illustrate the potential of neuroscience to address some of the pressing questions in Addiction Medicine. PMID- 26822370 TI - Preface: Neuroscience for Addiction Medicine: From Prevention to Rehabilitation. PMID- 26822371 TI - Psychotropic drug use among 0-17 year olds during 2004-2014: a nationwide prescription database study. AB - BACKGROUND: Time-trend studies on psychotropic drugs among children and adolescents are scarce, and most of them are outdated. The purpose of this study was to study prevalences of psychotropic drug use during 2004-2014 among Norwegians aged <18 years, overall and in psychotropic sub-groups. METHODS: Data were obtained from the Norwegian Prescription Database, which covers all dispensed prescription drugs in Norway from 2004 and onwards. Psychotropic drugs included: antipsychotics (ATC-group N05A), anxiolytics (N05B), hypnotic/sedatives (N05C), antidepressants (N06A), stimulants (N06BA), and alimemazine (R06AD01). Period (1-year) prevalence of use, overall and in subgroups of psychotropic drugs, was estimated by identifying individuals <18 years who had at least one psychotropic drug dispensed during each year. RESULTS: Psychotropic drug use increased in 0-17 year olds over an 11-year period, in which the main contributing drugs were stimulants (boys overall; 15.0 to 20.8/1000, girls overall; 3.8 to 8.5/1000), hypnotic/sedative drugs in adolescents (boys overall; 4.2 to 10.8/1000, girls overall; 2.6 to 8.8/1000) and to some extent antidepressants among adolescent girls (girls overall from 3.1 to 4.0/1000). Psychotropic drug use was, however, reduced by half in the youngest children, attributed to reduction of alimemazine only (1-year olds: boys; from 36.6 to 10.2/1000, girls; 26.9 to 7.2/1000). A higher level of psychotropic drug use was observed among younger boys, but there is a shift towards girls using more psychotropic drugs than boys during adolescence for all psychotropic drugs except for stimulants. CONCLUSION: Different trends in psychotropic drug use exist in age and gender subgroups. Psychotropic drug use has decreased among the youngest children, attributed to alimemazine, and increased in older children and adolescents, attributed mainly to stimulants and hypnotics/sedatives. PMID- 26822372 TI - Zebra sign of precentral gyri in amyotrophic lateral sclerosis: A novel finding using phase difference enhanced (PADRE) imaging-initial results. AB - OBJECTIVE: We compared the precentral gyri (PG) on the PADRE of patients with amyotrophic lateral sclerosis (ALS) and healthy subjects (HSs) in order to determine whether it is possible to discriminate between ALS patients and HSs on an individual basis. METHODS: First, two radiologists reviewed the appearance of the normal PG and that of ALS patients on PADRE in a non-blinded manner, and deviations from the appearance of the normal PG were recorded. Next, based on the presence of PG abnormalities on PADRE, we performed an observer performance study using 16 ALS patients and 16 HSs. RESULTS: The radiologists were able to consensually define the PG as abnormal on PADRE when a low-signal-intensity layer was observed in the gray matter of the PG; a three- or four-layer organization (zebra sign) was characterized by the low-signal-intensity layer. The observer performance study demonstrated that the sensitivity, specificity, and accuracy of PG abnormalities on PADRE for discriminating ALS patients from HSs were 94 %, 94 %, and 94 %, respectively, for reviewers 1 and 2. CONCLUSIONS: It was possible to discriminate between ALS patients and HSs based on the presence of PG abnormalities on PADRE, which may reflect upper motor neuron impairment in ALS. KEY POINTS: * PADRE reveals low-signal-intensity layer in the PG of ALS * By PADRE findings on PG, we can discriminate ALS from HSs * PADRE may be a useful method for detecting UMN impairment in ALS. PMID- 26822373 TI - Regional thermochemotherapy versus hepatic arterial infusion chemotherapy for palliative treatment of advanced hilar cholangiocarcinoma: a retrospective controlled study. AB - OBJECTIVES: To retrospectively assess the efficacy of regional thermochemotherapy (TCT) compared with hepatic arterial infusion chemotherapy (HAIC)-alone for palliative treatment of advanced hilar cholangiocarcinoma (HC) and to determine the prognostic factors associated with survival. METHODS: Forty-three consecutive patients with advanced HC underwent regional TCT (TCT group) and HAIC (HAIC group). We analyzed baseline characteristics, overall survival (OS), progression free survival (PFS), stent patency time (SPT), adverse events (AEs), and prognostic factors for OS between the two groups. RESULTS: OS of patients treated with regional TCT was significantly longer compared to that of patients treated with HAIC (median OS: 20.3 vs. 13.2 months, P = 0.004), and SPT and PFS were significantly increased in the TCT group compared with the HAIC group (median SPT: 26.5 vs. 10.5 months, P < 0.001; median PFS: 16.5 vs. 10.2 months, P = 0.001). TCT and metal stent insertion were two independent prognostic factors associated with survival. The treatment-related AEs were tolerable and similar in the two groups, except for hilar pain (34.6 %) and skin rashes (24.6 %) in the TCT group. CONCLUSIONS: Our results show that regional TCT is safe and more effective than HAIC-alone and may be a promising option for palliative treatment of advanced HC. Metal stenting before TCT appears to improve patients' OS. KEY POINTS: * Regional TCT is a novel combination for palliative treatment of advanced HC * Our data showed significantly promising outcomes in the TCT group * HC patients with metal stenting appeared to derive greater benefit from TCT. PMID- 26822374 TI - The quality of reporting methods and results of cost-effectiveness analyses in Spain: a methodological systematic review. AB - BACKGROUND: Cost-effectiveness analysis has been recognized as an important tool to determine the efficiency of healthcare interventions and services. There is a need for evaluating the reporting of methods and results of cost-effectiveness analyses and establishing their validity. We describe and examine reporting characteristics of methods and results of cost-effectiveness analyses conducted in Spain during more than two decades. METHODS: A methodological systematic review was conducted with the information obtained through an updated literature review in PubMed and complementary databases (e.g. Scopus, ISI Web of Science, National Health Service Economic Evaluation Database (NHS EED) and Health Technology Assessment (HTA) databases from Centre for Reviews and Dissemination (CRD), Indice Medico Espanol (IME) Indice Bibliografico Espanol en Ciencias de la Salud (IBECS)). We identified cost-effectiveness analyses conducted in Spain that used quality-adjusted life years (QALYs) as outcome measures (period 1989 December 2014). Two reviewers independently extracted the data from each paper. The data were analysed descriptively. RESULTS: In total, 223 studies were included. Very few studies (10; 4.5 %) reported working from a protocol. Most studies (200; 89.7 %) were simulation models and included a median of 1000 patients. Only 105 (47.1 %) studies presented an adequate description of the characteristics of the target population. Most study interventions were categorized as therapeutic (189; 84.8 %) and nearly half (111; 49.8 %) considered an active alternative as the comparator. Effectiveness of data was derived from a single study in 87 (39.0 %) reports, and only few (40; 17.9 %) used evidence synthesis-based estimates. Few studies (42; 18.8 %) reported a full description of methods for QALY calculation. The majority of the studies (147; 65.9 %) reported that the study intervention produced "more costs and more QALYs" than the comparator. Most studies (200; 89.7 %) reported favourable conclusions. Main funding source was the private for-profit sector (135; 60.5 %). Conflicts of interest were not disclosed in 88 (39.5 %) studies. CONCLUSIONS: This methodological review reflects that reporting of several important aspects of methods and results are frequently missing in published cost-effectiveness analyses. Without full and transparent reporting of how studies were designed and conducted, it is difficult to assess the validity of study findings and conclusions. PMID- 26822376 TI - Severe and Less Severe Intimate Partner Violence: From Characterization to Prediction. AB - Intimate partner homicide/attempted homicide are the most serious outcome of intimate partner violence. Thus, in this study, conducted in Portugal, we sought to compare perpetrators of severe violence with those who perpetrate less severe acts of violence as well as to identify predictors for severe violence. Sample was constituted by 50 men convicted for marital homicide or attempted homicide and 137 men convicted for domestic violence. Results show that although both perpetrators of severe and less severe violence share some characteristics, significant differences were found among them. The use of weapons, separation/break-up, and high socioeconomic status (SES) significantly increased the likelihood of a man to commit severe violence. Prior violence, aggression, and medium SES decreased significantly the probability of an individual to perpetrate severe violence. These findings reinforce the assumption that severe and less severe forms of violence can be discrete phenomena and underscore the importance of conducting accurate risk assessments. PMID- 26822375 TI - Prevalence and risk factors for viral exposure in rural dogs around protected areas of the Atlantic forest. AB - BACKGROUND: Despite the crucial role of domestic dogs as reservoirs for zoonosis and some of the most threatening diseases for wild carnivores such as distemper and parvovirosis, little is known about the epidemiological features and the risk factors involved in pathogen exposure of dogs that live in human/wildlife interfaces and actually contacts wildlife. Through a cross-sectional serological approach and questionnaire survey, we assessed the prevalence along with individual and environment-associated risk factors for four important viral diseases of rural dogs living in households around six Atlantic Forest fragments in southeast Brazil. RESULTS: Widespread exposure to canine parvovirus (97%), canine distemper virus (15%) and canine adenovirus (27%) was detected, but none for canine coronavirus. Dogs from small private reserves were more exposed to parvovirus and canine distemper virus than those from larger state parks. Exposure was associated with dog sex and age, lack of health care and the number of people in the households. Remarkably, factors linked to free-ranging behaviour of dogs were associated with the exposure for all pathogens detected. CONCLUSIONS: According to identified associations, reducing viral pathogen exposure in dogs will require inhibiting dog's movements and access to nearby forests and villages and improving veterinary assistance. Promoting dog vaccination and population control through sterilization around protected areas is also necessary. The study provides support for preventive management actions aimed to protect the health of rural dogs, and consequently of Atlantic Forest's wild carnivores. PMID- 26822377 TI - Obesity is not always the answer. PMID- 26822378 TI - Pyridyl Pyrrolide Boron Complexes: The Facile Generation of Thermally Activated Delayed Fluorescence and Preparation of Organic Light-Emitting Diodes. AB - The electron positive boron atom usually does not contribute to the frontier orbitals for several lower-lying electronic transitions, and thus is ideal to serve as a hub for the spiro linker of light-emitting molecules, such that the electron donor (HOMO) and acceptor (LUMO) moieties can be spatially separated with orthogonal orientation. On this basis, we prepared a series of novel boron complexes bearing electron deficient pyridyl pyrrolide and electron donating phenylcarbazolyl fragments or triphenylamine. The new boron complexes show strong solvent-polarity dependent charge-transfer emission accompanied by a small, non negligible normal emission. The slim orbital overlap between HOMO and LUMO and hence the lack of electron correlation lead to a significant reduction of the energy gap between the lowest lying singlet and triplet excited states (DeltaET-S ) and thereby the generation of thermally activated delay fluorescence (TADF). PMID- 26822379 TI - Expression of programmed death ligand-1 on tumor cells varies pre and post chemotherapy in non-small cell lung cancer. AB - The effects of treatments to programmed death ligand-1 (PD-L1) expression is unknown. The aim of this study was to investigate the impact of neoadjuvant chemotherapy (NACT) on PD-L1 expression in non-small cell lung cancer (NSCLC) patients. PD-L1 expression was detected by immunohistochemistry (IHC) method in 32 paired tumor specimens pre and post-NACT. The positivity of PD-L1 on tumor cells (TCs) changed from 75% to 37.5% after NACT (p = 0.003). Cases with IHC score of 1, 2, 3 all underwent apparent decrease (p = 0.007). However, no significant changes were observed on tumour-infiltrating immune cells (ICs) (p = 0.337). Subgroup and semiquantitative analyses all presented similar results. Moreover, patients with response to NACT presented significantly reduced PD-L1 expression on TCs (p = 0.004). Although it was not confirmed by the Cox proportional hazard regression model, there was an apparent difference in disease free-survival (DFS) between negative-to-positive switch of PD-L1 status and the contrary group (median DFS: 9.6 versus 25.9, p = 0.005). Our data revealed that antecedent chemotherapy for NSCLC may results in inconsistency of PD-L1 expression. PD-L1 expression is suggested to be monitored around treatment and on serial samples, at least, on the latest tumor specimen. PMID- 26822380 TI - Remission of Severe Myasthenia Gravis After Massive-Dose Vitamin D Treatment. AB - BACKGROUND: Vitamin D has been shown to be related to autoimmune diseases, such as multiple sclerosis and psoriasis. Correlations have been reported between vitamin D levels and prevalence and severity of other autoimmune disorders, and also between vitamin D therapy and disease improvement and remission. CASE REPORT: This is a case report of a patient with severe and refractory myasthenia gravis (MG) who followed a "high-dose vitamin D treatment", a massive-dose treatment (80,000 to 120,000 IU/day) promoted by a medical center in Brazil (but still not proven), and she had her first complete remission after this type of treatment with increased vitamin D serum levels (400 to 700 ng/mL). CONCLUSIONS: This case report may reinforce the reported correlation between vitamin D level and disease severity and introduces a possible new use for vitamin D as a potential target for treating autoimmune diseases. We recommend large, double blind, placebo-controlled, randomized studies using high-dose vitamin D treatment for refractory autoimmune diseases to reliably assess this pharmacotherapy target for these diseases. PMID- 26822381 TI - Causes and outcomes of new onset status epilepticus and predictors of refractoriness to therapy. AB - We aimed to evaluate the determinants of outcome in new onset refractory status epilepticus (SE). A retrospective analysis of patients with new onset SE admitted between May 2005 and October 2013 was performed. Regression analysis was used to determine factors that affect progression of new onset SE to refractory status epilepticus (RSE) and mortality. Among 114 patients with new onset SE, 52 patients progressed to RSE. Sixty seven (58.7%) were men. New onset RSE patients were younger than new onset SE patients (mean 35.9 +/- standard deviation18.2 versus 28.7 +/- 20.2 years; p=0.050). Cryptogenic aetiology was the most significant determinant of progression of new onset SE to RSE (Exp [beta]=5.68; p=0.001). The overall mortality in the entire group was 23.7%, significantly higher in new onset RSE group (40.4% versus 9.7%; p<0.0001). New onset RSE patients with symptomatic and cryptogenic etiology did not differ for clinical characteristics and outcome. Acidosis was the strongest predictor of mortality in the entire cohort (Exp [beta]=8.72; p=0.005). Nearly half of the patients with new onset SE progressed to RSE. While cryptogenic aetiology determined progression of new onset SE to RSE, acidosis was associated with mortality. The outcome was similar between symptomatic and cryptogenic new onset RSE. PMID- 26822384 TI - The Index of Microcirculatory Resistance Postpercutaneous Coronary Intervention Predicts Left Ventricular Recovery in Patients With Thrombolyzed ST-Segment Elevation Myocardial Infarction. AB - BACKGROUND: The index of microcirculatory resistance (IMR), an invasive measure of microvascular function, has been shown to correlate with clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study is to evaluate the predictive value of IMR on left ventricular recovery in patients undergoing a pharmacoinvasive strategy for STEMI. METHODS: The index of microcirculatory resistance was assessed following percutaneous coronary intervention (PCI) in 31 patients with STEMI who were initially managed with thrombolysis. Other markers of microvascular function such as coronary flow reserve (CFR), TIMI flow grade, corrected TIMI frame count (cTFC), and ST-segment resolution were also recorded. All indices were evaluated against measures of left ventricular function and recovery 3 months postindex event. RESULTS: The IMR correlated with left ventricular function, as assessed by wall motion score and ejection fraction at 3-month follow-up (r = 0.652, P = 0.005; r = -0.452, P = 0.011, respectively). The traditional methods of assessing microvascular function, such as CFR, TIMI flow grade, cTFC, and ST-segment resolution did not correlate with wall motion score and ejection fraction at 3 months. Post-PCI IMR was significantly lower in those patients with left ventricular recovery at 3 months (18 U vs 39 U, P < 0.001). The optimal cut-off value for post-PCI IMR and left ventricular recovery was 32 U. In patients in whom the IMR was greater than 32 U, the percent change in ejection fraction was significantly lower than in those patients in whom the IMR was less than 32 U (2 +/- 11 vs 12 +/- 8, P = 0.012). CONCLUSIONS: In patients presenting with STEMI initially managed with thrombolysis and subsequently undergoing PCI, IMR correlates with measures of left ventricular function and has the potential to predict left ventricular recovery at 3 months. PMID- 26822385 TI - Hydrothermal Synthesis of TiO2@SnO2 Hybrid Nanoparticles in a Continuous-Flow Dual-Stage Reactor. AB - TiO2@SnO2 hybrid nanocomposites were successfully prepared in gram scale using a dual-stage hydrothermal continuous-flow reactor. Temperature and pH in the secondary reactor were found to selectively direct nucleation and growth of the secondary material into either heterogeneous nanocomposites or separate intermixed nanoparticles. At low pH, 2 nm rutile SnO2 nanoparticles were deposited on 9 nm anatase TiO2 particles; the presence of TiO2 was found to suppress formation of larger SnO2 particles. At high pH SnO2 formed separate particles and no deposition on TiO2 was observed. Ball-milling of TiO2 and SnO2 produced no TiO2@SnO2 composites. This verifies that the composite particles must be formed by nucleation and growth of the secondary precursor on the TiO2 . High concentration of secondary precursor led to formation of TiO2 particles embedded in aggregates of SnO2 nanoparticles. The results demonstrate how nanocomposites may be produced in high yield by green chemistry. PMID- 26822382 TI - Transfer of the methicillin resistance genomic island among staphylococci by conjugation. AB - Methicillin resistance creates a major obstacle for treatment of Staphylococcus aureus infections. The resistance gene, mecA, is carried on a large (20 kb to > 60 kb) genomic island, staphylococcal cassette chromosome mec (SCCmec), that excises from and inserts site-specifically into the staphylococcal chromosome. However, although SCCmec has been designated a mobile genetic element, a mechanism for its transfer has not been defined. Here we demonstrate the capture and conjugative transfer of excised SCCmec. SCCmec was captured on pGO400, a mupirocin-resistant derivative of the pGO1/pSK41 staphylococcal conjugative plasmid lineage, and pGO400::SCCmec (pRM27) was transferred by filter-mating into both homologous and heterologous S. aureus recipients representing a range of clonal complexes as well as S. epidermidis. The DNA sequence of pRM27 showed that SCCmec had been transferred in its entirety and that its capture had occurred by recombination between IS257/431 elements present on all SCCmec types and pGO1/pSK41 conjugative plasmids. The captured SCCmec excised from the plasmid and inserted site-specifically into the chromosomal att site of both an isogenic S. aureus and a S. epidermidis recipient. These studies describe a means by which methicillin resistance can be environmentally disseminated and a novel mechanism, IS-mediated recombination, for the capture and conjugative transfer of genomic islands. PMID- 26822386 TI - Highly Conductive and Thermally Stable Ion Gels with Tunable Anisotropy and Modulus. AB - A new liquid-crystalline ion gel exhibits unprecedented properties: conductivity up to 8 mS cm(-1) , thermal stability to 300 degrees C, and electrochemical window to 6.1 V, as well as adjustable transport anisotropy (up to 3.5*) and elastic modulus (0.03-3 GPa). The combination of ionic liquid and magnetically oriented rigid-rod polyanion provides widely tunable properties for use in diverse electrochemical devices. PMID- 26822383 TI - Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy. AB - Anti-PD-1 therapy yields objective clinical responses in 30-40% of advanced melanoma patients. Since most patients do not respond, predictive biomarkers to guide treatment selection are needed. We hypothesize that MHC-I/II expression is required for tumour antigen presentation and may predict anti-PD-1 therapy response. In this study, across 60 melanoma cell lines, we find bimodal expression patterns of MHC-II, while MHC-I expression was ubiquitous. A unique subset of melanomas are capable of expressing MHC-II under basal or IFNgamma stimulated conditions. Using pathway analysis, we show that MHC-II(+) cell lines demonstrate signatures of 'PD-1 signalling', 'allograft rejection' and 'T-cell receptor signalling', among others. In two independent cohorts of anti-PD-1 treated melanoma patients, MHC-II positivity on tumour cells is associated with therapeutic response, progression-free and overall survival, as well as CD4(+) and CD8(+) tumour infiltrate. MHC-II(+) tumours can be identified by melanoma specific immunohistochemistry using commercially available antibodies for HLA-DR to improve anti-PD-1 patient selection. PMID- 26822387 TI - A new species of Gobius (Perciformes: Gobiidae) from the Mediterranean Sea and the redescription of Gobius bucchichi. AB - A new species of the gobiid genus Gobius (Gobiidae, Perciformes), Gobius incognitus sp. nov. is described from the Mediterranean Sea, and its most morphologically similar species Gobius bucchichi is redescribed. The new species is distinguished from its congeners by: scales in lateral series 51-59; predorsal scales 25-35; opercle scaled in adults with 10-16 scales present; pectoral fin with ray count 18-20 and free tips on upper rays well developed and on the first ray longer than two thirds of the entire ray length; pelvic disc complete and with well-developed anterior membrane without lateral lobes; anterior oculoscapular canal with pore alpha at rear of orbit; oculoscapular row x(1) not extending forwards to pore beta; suborbital row d discontinuous with large gap below suborbital rows 3 and 4; eye diameter 1.08-1.32 in snout length; by pigment rows on cheek and pigmentation on pectoral-fin base. PMID- 26822388 TI - Evaluation of Electrostimulation Effect in Women With Vocal Nodules. AB - OBJECTIVE: To evaluate the effect of transcutaneous electrical nerve stimulation (TENS) with and without tongue trills in women with vocal nodules. STUDY DESIGN: Randomized, prospective, comparative intra-subject study. METHODS: A total of 60 women aged 18-55 years were included. Visual-perceptual assessment of laryngeal configuration, auditory-perceptual assessment of voice quality, acoustic analyses, and self-assessment of phonation effort were assessed after TENS. Sixty participants participants were randomized into two experimental groups: (1) subjects receiving TENS (EG1), (2) subjects receiving TENS plus tongue trills (EG2). The control group was composed of 15 subjects of EG1 and 15 subjects of EG2. The TENS condition involved electrostimulation for 20 minutes. Audio and video perceptual assessments were performed by three speech therapists with expertise in voice; all were blinded to the experimental conditions. The acoustic parameters included were fundamental frequency, jitter, and shimmer during sustained phonation. Subjects also reported the degree of vocal effort before and after TENS. RESULTS: TENS applied alone or combined with tongue trills aided in glottal closure and in improved comfort during phonation. When the TENS was administered with tongue trills, roughness of voice quality improved. CONCLUSION: TENS applied alone or combined with tongue trills was associated with improved glottal closure and phonation comfort. TENS associated with tongue trills yielded improved voice quality. PMID- 26822389 TI - Acoustic Properties of the Voice Source and the Vocal Tract: Are They Perceptually Independent? AB - OBJECTIVE/HYPOTHESIS: This study sought to determine whether the properties of the voice source and vocal tract are perceptually independent. STUDY DESIGN: Within-subjects design. METHODS: This study employed a paired-comparison paradigm where listeners heard synthetic voices and rated them as same or different using a visual analog scale. Stimuli were synthesized using three different source slopes and two different formant patterns (mezzo-soprano and soprano) on the vowel /a/ at four pitches: A3, C4, B4, and F5. RESULTS: Whereas formant pattern was the strongest effect, difference in source slope also affected perceived quality difference. Source slope and formant pattern were not independently perceived. CONCLUSION: These results suggest that when judging laryngeal adduction using perceptual information, judgments may not be accurate when the stimuli are of differing formant patterns. PMID- 26822390 TI - Gastrointestinal dysmotility disorders in critically ill dogs and cats. AB - OBJECTIVE: To review the human and veterinary literature regarding gastrointestinal (GI) dysmotility disorders in respect to pathogenesis, patient risk factors, and treatment options in critically ill dogs and cats. ETIOLOGY: GI dysmotility is a common sequela of critical illness in people and small animals. The most common GI motility disorders in critically ill people and small animals include esophageal dysmotility, delayed gastric emptying, functional intestinal obstruction (ie, ileus), and colonic motility abnormalities. Medical conditions associated with the highest risk of GI dysmotility include mechanical ventilation, sepsis, shock, trauma, systemic inflammatory response syndrome, and multiple organ failure. The incidence and pathophysiology of GI dysmotility in critically ill small animals is incompletely understood. DIAGNOSIS: A presumptive diagnosis of GI dysmotility is often made in high-risk patient populations following detection of persistent regurgitation, vomiting, lack of tolerance of enteral nutrition, abdominal pain, and constipation. Definitive diagnosis is established via radioscintigraphy; however, this diagnostic tool is not readily available and is difficult to perform on small animals. Other diagnostic modalities that have been evaluated include abdominal ultrasonography, radiographic contrast, and tracer studies. THERAPY: Therapy is centered at optimizing GI perfusion, enhancement of GI motility, and early enteral nutrition. Pharmacological interventions are instituted to promote gastric emptying and effective intestinal motility and prevention of complications. Promotility agents, including ranitidine/nizatidine, metoclopramide, erythromycin, and cisapride are the mainstays of therapy in small animals. PROGNOSIS: The development of complications related to GI dysmotility (eg, gastroesophageal reflux and aspiration) have been associated with increased mortality risk. Institution of prophylaxic therapy is recommended in high-risk patients, however, no consensus exists regarding optimal timing of initiating prophylaxic measures, preference of treatment, or duration of therapy. The prognosis for affected small animal patients remains unknown. PMID- 26822391 TI - Interspecific variation in localization of hypericins and phloroglucinols in the genus Hypericum as revealed by desorption electrospray ionization mass spectrometry imaging. AB - Plants of the genus Hypericum are widely known for their therapeutic properties. The most biologically active compounds of this genus are naphtodianthrones and phloroglucinols. Indirect desorption electrospray ionization mass spectrometry (DESI-MS) imaging allows visualization and localization of secondary metabolites in different plant tissues. This study is focused on localization of major secondary compounds in the leaves of 17 different in vitro cultured Hypericum species classified in 11 sections. Generally, all identified naphtodianthrones, protohypericin, hypericin, protopseudohypericin and pseudohypericin were co localized in the dark glands of eight hypericin producing species at the site of their accumulation. The known phloroglucinols, hyperforin, adhyperforin, hyperfirin and some new phloroglucinols with m/z [M - H](-) 495 and 569 were localized in the translucent and pale cavities within the leaf in the majority of studied species. The comparison of different Hypericum species revealed an interspecific variation in the distribution of the dark and translucent glands corresponding with the localization of hypericins and phloroglucinols. Moreover, similarities in the localization and composition of the phloroglucinols were observed in the species belonging to the same section. Adding to various quantitative studies focused on the detection of secondary metabolites, this work using indirect DESI-MSI offers additional valuable information about localization of the above-mentioned compounds. PMID- 26822392 TI - Environmental effects of ozone depletion and its interactions with climate change: progress report, 2015. AB - The Environmental Effects Assessment Panel (EEAP) is one of three Panels that regularly informs the Parties (countries) to the Montreal Protocol on the effects of ozone depletion and the consequences of climate change interactions with respect to human health, animals, plants, biogeochemistry, air quality, and materials. The Panels provide a detailed assessment report every four years. The most recent 2014 Quadrennial Assessment by the EEAP was published as a special issue of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). The next Quadrennial Assessment will be published in 2018/2019. In the interim, the EEAP generally produces an annual update or progress report of the relevant scientific findings. The present progress report for 2015 assesses some of the highlights and new insights with regard to the interactive nature of the effects of UV radiation, atmospheric processes, and climate change. PMID- 26822393 TI - CuSO4/H2O2-Induced Rapid Deposition of Polydopamine Coatings with High Uniformity and Enhanced Stability. AB - Mussel-inspired polydopamine (PDA) deposition offers a promising route to fabricate multifunctional coatings for various materials. However, PDA deposition is generally a time-consuming process, and PDA coatings are unstable in acidic and alkaline media, as well as in polar organic solvents. We report a strategy to realize the rapid deposition of PDA by using CuSO4/H2O2 as a trigger. Compared to the conventional processes, our strategy shows the fastest deposition rate reported to date, and the PDA coatings exhibit high uniformity and enhanced stability. Furthermore, the PDA-coated porous membranes have excellent hydrophilicity, anti-oxidant properties, and antibacterial performance. This work demonstrates a useful method for the environmentally friendly, cost-effective, and time-saving fabrication of PDA coatings. PMID- 26822394 TI - Independent Control of the Magnetization in Ferromagnetic La2/3Sr1/3MnO3/SrTiO3/LaCoO3 Heterostructures Achieved by Epitaxial Lattice Mismatch. AB - We report the effect of interface symmetry-mismatch on the magnetic properties of LaCoO3 (LCO) thin films. Growing epitaxial LCO under tensile strain on top of cubic SrTiO3 (STO) produces a contraction along the c axis and a characteristic ferromagnetic response. However, we report here that ferromagnetism in LCO is completely suppressed when grown on top of a buffer layer of rhombohedral La2/3Sr1/3MnO3 (LSMO), in spite of identical in-plane and out-of-plane lattice deformation. This confirms that it is the lattice symmetry mismatch and not just the total strain, which determines the magnetism of LCO. On the basis of this control over the magnetic properties of LCO, we designed a multilayered structure to achieve independent rotation of the magnetization in ferromagnetic insulating LCO and half-metallic ferromagnet LSMO. This is an important step forward for the design of spin-filtering tunnel barriers based on LCO. PMID- 26822395 TI - Layered Black Phosphorus: Strongly Anisotropic Magnetic, Electronic, and Electron Transfer Properties. AB - Layered elemental materials, such as black phosphorus, exhibit unique properties originating from their highly anisotropic layered structure. The results presented herein demonstrate an anomalous anisotropy for the electrical, magnetic, and electrochemical properties of black phosphorus. It is shown that heterogeneous electron transfer from black phosphorus to outer- and inner-sphere molecular probes is highly anisotropic. The electron-transfer rates differ at the basal and edge planes. These unusual properties were interpreted by means of calculations, manifesting the metallic character of the edge planes as compared to the semiconducting properties of the basal plane. This indicates that black phosphorus belongs to a group of materials known as topological insulators. Consequently, these effects render the magnetic properties highly anisotropic, as both diamagnetic and paramagnetic behavior can be observed depending on the orientation in the magnetic field. PMID- 26822396 TI - Using concept maps and goal-setting to support the development of self-regulated learning in a problem-based learning curriculum. AB - Problem-based learning (PBL) in medical education focuses on preparing independent learners for continuing, self-directed, professional development beyond the classroom. Skills in self-regulated learning (SRL) are important for success in PBL and ongoing professional practice. However, the development of SRL skills is often left to chance. This study presents the investigated outcomes for students when support for the development of SRL was embedded in a PBL medical curriculum. This investigation involved design, delivery and testing of SRL support, embedded into the first phase of a four-year, graduate-entry MBBS degree. The intervention included concept mapping and goal-setting activities through iterative processes of planning, monitoring and reflecting on learning. A mixed-methods approach was used to collect data from seven students to develop case studies of engagement with, and outcomes from, the SRL support. The findings indicate that students who actively engaged with support for SRL demonstrated increases in cognitive and metacognitive functioning. Students also reported a greater sense of confidence in and control over their approaches to learning in PBL. This study advances understanding about how the development of SRL can be integrated into PBL. PMID- 26822397 TI - Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. AB - BACKGROUND: Chemotherapy is the standard of care for incurable advanced gastric cancer. Whether the addition of gastrectomy to chemotherapy improves survival for patients with advanced gastric cancer with a single non-curable factor remains controversial. We aimed to investigate the superiority of gastrectomy followed by chemotherapy versus chemotherapy alone with respect to overall survival in these patients. METHODS: We did an open-label, randomised, phase 3 trial at 44 centres or hospitals in Japan, South Korea, and Singapore. Patients aged 20-75 years with advanced gastric cancer with a single non-curable factor confined to either the liver (H1), peritoneum (P1), or para-aortic lymph nodes (16a1/b2) were randomly assigned (1:1) in each country to chemotherapy alone or gastrectomy followed by chemotherapy by a minimisation method with biased-coin assignment to balance the groups according to institution, clinical nodal status, and non-curable factor. Patients, treating physicians, and individuals who assessed outcomes and analysed data were not masked to treatment assignment. Chemotherapy consisted of oral S-1 80 mg/m(2) per day on days 1-21 and cisplatin 60 mg/m(2) on day 8 of every 5-week cycle. Gastrectomy was restricted to D1 lymphadenectomy without any resection of metastatic lesions. The primary endpoint was overall survival, analysed by intention to treat. This study is registered with UMIN-CTR, number UMIN000001012. FINDINGS: Between Feb 4, 2008, and Sept 17, 2013, 175 patients were randomly assigned to chemotherapy alone (86 patients) or gastrectomy followed by chemotherapy (89 patients). After the first interim analysis on Sept 14, 2013, the predictive probability of overall survival being significantly higher in the gastrectomy plus chemotherapy group than in the chemotherapy alone group at the final analysis was only 13.2%, so the study was closed on the basis of futility. Overall survival at 2 years for all randomly assigned patients was 31.7% (95% CI 21.7-42.2) for patients assigned to chemotherapy alone compared with 25.1% (16.2 34.9) for those assigned to gastrectomy plus chemotherapy. Median overall survival was 16.6 months (95% CI 13.7-19.8) for patients assigned to chemotherapy alone and 14.3 months (11.8-16.3) for those assigned to gastrectomy plus chemotherapy (hazard ratio 1.09, 95% CI 0.78-1.52; one-sided p=0.70). The incidence of the following grade 3 or 4 chemotherapy-associated adverse events was higher in patients assigned to gastrectomy plus chemotherapy than in those assigned to chemotherapy alone: leucopenia (14 patients [18%] vs two [3%]), anorexia (22 [29%] vs nine [12%]), nausea (11 [15%] vs four [5%]), and hyponatraemia (seven [9%] vs four [5%]). One treatment-related death occurred in a patient assigned to chemotherapy alone (sudden cardiopulmonary arrest of unknown cause during the second cycle of chemotherapy) and one occurred in a patient assigned to chemotherapy plus gastrectomy (rapid growth of peritoneal metastasis after discharge 12 days after surgery). INTERPRETATION: Since gastrectomy followed by chemotherapy did not show any survival benefit compared with chemotherapy alone in advanced gastric cancer with a single non-curable factor, gastrectomy cannot be justified for treatment of patients with these tumours. FUNDING: The Ministry of Health, Labour and Welfare of Japan and the Korean Gastric Cancer Association. PMID- 26822398 TI - Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial. AB - BACKGROUND: Trastuzumab resistance is a key therapeutic challenge in metastatic breast cancer. We postulated that broader inhibition of ErbB receptors with afatinib would improve clinical outcomes compared with HER2 inhibition alone in patients who had progressed on previous trastuzumab treatment. LUX-Breast 1 compared afatinib plus vinorelbine with trastuzumab plus vinorelbine for such patients with HER2-positive metastatic breast cancer. METHODS: We did this open label trial at 350 hospitals in 41 countries worldwide. We enrolled female patients with HER2-overexpressing metastatic breast cancer who had progressed on or following adjuvant trastuzumab or first-line treatment of metastatic disease with trastuzumab. Participants were randomly assigned (2:1) to receive oral afatinib (40 mg/day) plus intravenous vinorelbine (25 mg/m(2) per week) or intravenous trastuzumab (2 mg/kg per week after 4 mg/kg loading dose) plus vinorelbine. Randomisation was done centrally and stratified by previous trastuzumab treatment (adjuvant vs first-line treatment), hormone receptor status (oestrogen receptor and progesterone receptor positive vs others), and region. The primary endpoint was progression-free survival, assessed in the intention-to treat population. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT01125566. FINDINGS: Between Aug 26, 2010, and April 26, 2013, we enrolled 508 patients: 339 assigned to the afatinib group and 169 assigned to the trastuzumab group. Recruitment was stopped on April 26, 2013, after a benefit-risk assessment by the independent data monitoring committee was unfavourable for the afatinib group. Patients on afatinib plus vinorelbine had to switch to trastuzumab plus vinorelbine, afatinib monotherapy, vinorelbine monotherapy, or receive treatment outside of the trial. Median follow-up was 9.3 months (IQR 3.7-16.0). Median progression-free survival was 5.5 months (95% CI 5.4-5.6) in the afatinib group and 5.6 months (5.3-7.3) in the trastuzumab group (hazard ratio 1.10 95% CI 0.86-1.41; p=0.43). The most common drug-related adverse events of grade 3 or higher were neutropenia (190 [56%] of 337 patients in the afatinib group vs 102 [60%] of 169 patients in the trastuzumab group), leucopenia (64 [19%] vs 34 [20%]), and diarrhoea (60 [18%] vs none). INTERPRETATION: Trastuzumab-based therapy remains the treatment of choice for patients with HER2-positive metastatic breast cancer who had progressed on trastuzumab. FUNDING: Boehringer Ingelheim. PMID- 26822399 TI - Lessons from breast cancer trials of HER2-kinase inhibitors. PMID- 26822400 TI - Different sealing materials preventing the microbial leakage into the screw retained implant restorations: an in vitro analysis by DNA checkerboard hybridization. AB - OBJECTIVES: The aim of this controlled in vitro study was to identify and quantify up to 38 microbial species penetrating through the screw-retained implant prostheses with different sealing materials. MATERIAL AND METHODS: Sixty morse cone implants were restored with single-unit screw-retained prostheses. All the components were randomly divided into five groups (n = 12) according to the proposed materials: (1) polytetrafluoroethylene tape+composite resin; (2) polytetrafluoroethylene tape+gutta-percha; (3) polytetrafluoroethylene tape+light polymerized provisional composite; (4) cotton pellet+gutta-percha; and (5) cotton pellet+light-polymerized provisional composite. Human saliva was used as contaminant media, and DNA checkerboard hybridization was used to identify and quantify microbial species. RESULTS: Microbial leakage was observed in all groups: M. salivarium, S. pasteuri, P. nigrescens, and P. melaninogenica were the species presenting the highest values of genome count, prevalence, and proportion within the groups. The total microbial mean counts (*105 , +/-SD) were as follows: Group 1 (2.81 +/- 0.38), Group 2 (3.41 +/- 0.38), Group 3 (6.02 +/- 1.48), Group 4 (6.40 +/- 1.42), and Group 5 (17.45 +/- 1.67). Group 5 showed the higher microbial counts (P < 0.001). CONCLUSIONS: Moderate to high counts of pathogenic/nonpathogenic species were detected in the inner parts of implants from all groups. The lowest values of microbial counts were recorded for polytetrafluoroethylene tape associated with composite resin or gutta-percha; cotton pellet associated with light-polymerized provisional composite presented the highest microbial counts. PMID- 26822401 TI - Albuminuria in type 2 diabetes mellitus: from remission to progression. AB - OBJECTIVE: Albuminuria is an early marker of renal impairment and a powerful factor of progression of renal disease in type 2 diabetes (T2D). Approximately, one-third of patients with T2D have micro- or macroalbuminuria and these patients have a high risk of progression toward End Stage Renal Disease (ESRD) as well as increased cardiovascular disease. The aim of this study was to determine the prevalence of remission, regression, persistence, and progression of albuminuria, and to evaluate the impact of change in albuminuria on kidney disease and cardiovascular disease in a prospective cohort of patients with T2D. METHODS: This is a prospective study. The Ethics Committee of Morocco's Mohammed V University in Rabat approved the study protocol. Inclusion criteria targeted patients who were type 2 diabetics with albuminuria >30 mg/day, and who had been regularly followed-up in nephrology consultation for at least 36 months. RESULTS: Five-hundred twenty-four patients were included. 75.8 and 24.6% of all patients had micro- and macroalbuminuria at enrollment in the study. At the end of the study, 91, 141, 199, and 93 patients had remission, regression, persistence, and progression of albuminuria, respectively. Remission of microalbuminuria to normoalbuminuria was observed in 23.6% of cases. Regression of macroalbuminuria to micro- was observed in 29.9% of cases. CONCLUSION: In our study, the incidence of remission and/or regression of micro- and macroalbuminuria was higher. The incidence of ESRD and the occurrence of cardiac events were greater in the regression, persistence, and progression groups than in the remission of albuminuria group. PMID- 26822402 TI - Neuroprotective Effects of Hydrogen Sulfide Against Early Brain Injury and Secondary Cognitive Deficits Following Subarachnoid Hemorrhage. AB - Although the neuroprotective effects of hydrogen sulfide (H2 S) have been demonstrated in several studies, whether H2 S protects against early brain injury (EBI) and secondary cognitive dysfunction in subarachnoid hemorrhage (SAH) model remains unknown. This study was undertaken to evaluate the influence of H2 S on both acute brain injury and neurobehavioral changes as well as the underlying mechanisms after SAH. The H2 S donor, NaHS, was administered via an intraperitoneal injection at a dose of 5.6 mg/kg at 2 h, 6 h, 24 h, and 46 h after SAH in rat model. The results showed that NaHS treatment significantly improved brain edema and neurobehavioral function, and attenuated neuronal cell death in the prefrontal cortex, associated with a decrease in Bax/Bcl-2 ratio and suppression of caspase-3 activation at 48 h after SAH. NaHS also promoted phospho Akt and phospho-ERK levels. Furthermore, NaHS treatment significantly enhanced the levels of brain-derived neurotrophic factor (BDNF) and phospho-CREB. Importantly, NaHS administration improved learning and memory performance in the Morris water maze test at 7 days post-SAH in rats. These results demonstrated that NaHS, as an exogenous H2 S donor, could significantly alleviate the development of EBI and cognitive dysfunction induced by SAH via Akt/ERK-related antiapoptosis pathway, and upregulating BDNF-CREB expression. PMID- 26822403 TI - A comparative study of diode laser and plasmakinetic in transurethral enucleation of the prostate for treating large volume benign prostatic hyperplasia: a randomized clinical trial with 12-month follow-up. AB - The objective of this study is to compare the efficacy and safety of diode laser enucleation of the prostate (DiLEP) with plasmakinetic enucleation of the prostate (PKEP) for symptomatic benign prostatic hyperplasia (BPH) patients with large prostate (volume > 80 ml). From January 2013 to June 2014, 80 consecutive patients were randomized treated with DiLEP (n = 40) or PKEP (n = 40). Perioperative and postoperative outcome data were assessed during a 1-year follow up. There were no significant preoperative differences between the two surgical groups. The mean prostate volumes in the DiLEP and PKEP groups were 98.6 and 93.3 ml, respectively. DiLEP was equivalent to PKEP in improvement in International Prostate Symptom Score (IPSS), quality of life scores, and maximum flow rate. Compared with PKEP, patients treated with DiLEP showed a lower risk of blood loss (P < 0.01), shorter bladder irrigation and catheterization times (P < 0.01), as well as shorter hospital stays (P < 0.01). Moreover, the DiLEP group was significantly superior to bipolar plasmakinetic group in the irritative symptoms. However, the operation time of the DiLEP group was longer than that of PKEP group (P = 0.02). Both DiLEP and PKEP are safe and effective methods for the treatment of BPH in large prostates (volume > 80 ml). Compared with PKEP, DiLEP provides a decreased risk of hemorrhage, reduced bladder irrigation, and catheterization times, as well as shorter hospital stays. PMID- 26822404 TI - Altered glycosylation of exported proteins, including surface immune receptors, compromises calcium and downstream signaling responses to microbe-associated molecular patterns in Arabidopsis thaliana. AB - BACKGROUND: Calcium, as a second messenger, transduces extracellular signals into cellular reactions. A rise in cytosolic calcium concentration is one of the first plant responses after exposure to microbe-associated molecular patterns (MAMPs). We reported previously the isolation of Arabidopsis thaliana mutants with a "changed calcium elevation" (cce) response to flg22, a 22-amino-acid MAMP derived from bacterial flagellin. RESULTS: Here, we characterized the cce2 mutant and its weaker allelic mutant, cce3. Besides flg22, the mutants respond with a reduced calcium elevation to several other MAMPs and a plant endogenous peptide that is proteolytically processed from pre-pro-proteins during wounding. Downstream defense-related events such flg22-induced mitogen-activated protein kinase activation, accumulation of reactive oxygen species and growth arrest are also attenuated in cce2/cce3. By genetic mapping, next-generation sequencing and allelism assay, CCE2/CCE3 was identified to be ALG3 (Asparagine-linked glycosylation 3). This encodes the alpha-1,3-mannosyltransferase responsible for the first step of core oligosaccharide Glc3Man9GlcNAc2 glycan assembly on the endoplasmic reticulum (ER) luminal side. Complementation assays and glycan analysis in yeast alg3 mutant confirmed the reduced enzymatic function of the proteins encoded by the cce2/cce3 alleles - leading to accumulation of M5(ER), the immature five mannose-containing oligosaccharide structure found in the ER. Proper protein glycosylation is required for ER/Golgi processing and trafficking of membrane proteins to the plasma membrane. Endoglycosidase H-insensitivity of flg22 receptor, FLS2, in the cce2/cce3 mutants suggests altered glycan structures in the receptor. CONCLUSION: Proper glycosylation of MAMP receptors (or other exported proteins) is required for optimal responses to MAMPs and is important for immune signaling of host plants. PMID- 26822405 TI - Laboratory Information Bulletin: Quantitation of Aflatoxin M1 in Bovine Milk by Liquid Chromatography with Fluorescence Detection. AB - An extraction for aflatoxin M1 from bovine milk samples is described. The samples were extracted by adding 10 mL acetonitrile to 10 g of sample. The extract was salted out with sodium chloride and magnesium sulfate to separate the water and acetonitrile. The organic layer was dried down and reconstituted in water before being subjected to an immunoaffinity column for cleanup. Once the analyte was isolated, quantitation was obtained by LC with fluorescence detection. LC/fluorescence parameters were optimized with an Agilent Poroshell 120 C18 LC column resulting in a 4 min run time. To test the procedure's robustness, three different kinds of matrixes were fortified at three different levels each. Whole milk, reduced fat milk, and skim milk samples were fortified at approximately 0.25, 0.5, and 1.0 MUg/kg. Recoveries from all samples ranged from 70 to 100%. Confirmation was accomplished by injecting the samples in an ion trap mass spectrometer. The method presented here entails an extraction step followed by an immunoaffinity column clean-up that leads to fast analysis time and consistent recoveries with an uncertainty measurement of 10.5% and method detection limit of less than 0.011 MUg/kg. PMID- 26822406 TI - Plasmodium vivax gametocyte infectivity in sub-microscopic infections. AB - BACKGROUND: The use of molecular techniques has put in the spotlight the existence of a large mass of malaria sub-microscopic infections among apparently healthy populations. These sub-microscopic infections are considered an important pool for maintained malaria transmission. METHODS: In order to assess the appearance of Plasmodium vivax gametocytes in circulation, gametocyte density and the parasite infectivity to Anopheles mosquitoes, a study was designed to compare three groups of volunteers either experimentally infected with P. vivax sporozoites (early infections; n = 16) or naturally infected patients (acute malaria, n = 16 and asymptomatic, n = 14). In order to determine gametocyte stage, a quantitative reverse transcriptase PCR (RT-qPCR) assay targeting two sexual stage-specific molecular markers was used. Parasite infectivity was assessed by membrane feeding assays (MFA). RESULTS: In early infections P. vivax gametocytes could be detected starting at day 7 without giving rise to infected mosquitoes during 13 days of follow-up. Asymptomatic carriers, with presumably long-lasting infections, presented the highest proportion of mature gametocytes and were as infective as acute patients. CONCLUSIONS: This study shows the potential role of P. vivax asymptomatic carriers in malaria transmission should be considered when new policies are envisioned to redirect malaria control strategies towards targeting asymptomatic infections as a tool for malaria elimination. PMID- 26822407 TI - The papers presented at 7th Young Scientists School "Systems Biology and Bioinformatics" (SBB'15): Introductory Note. Introduction. PMID- 26822408 TI - Growth map for Ga-assisted growth of GaAs nanowires on Si(111) substrates by molecular beam epitaxy. AB - For the Ga-assisted growth of GaAs nanowires on Si(111) substrates by molecular beam epitaxy, growth temperature, As flux, and Ga flux have been systematically varied across the entire window of growth conditions that result in the formation of nanowires. A range of GaAs structures was observed, progressing from pure Ga droplets under negligible As flux through horizontal nanowires, tilted nanowires, vertical nanowires, and nanowires without droplets to crystallites as the As flux was increased. Quantitative analysis of the resulting sample morphology was performed in terms of nanowire number and volume density, number yield and volume yield of vertical nanowires, diameter, length, as well as the number and volume density of parasitic growth. The result is a growth map that comprehensively describes all nanowire and parasitic growth morphologies and hence enables growth of nanowire samples in a predictive manner. Further analysis indicates the combination of global Ga flux and growth temperature determines the total density of all objects, whereas the global As/Ga flux ratio independently determines the resultant sample morphology. Several dependencies observed here imply that all objects present on the substrate surface, i.e. both nanowires and parasitic structures, originate from Ga droplets. PMID- 26822409 TI - Live-cell protein labelling with nanometre precision by cell squeezing. AB - Live-cell labelling techniques to visualize proteins with minimal disturbance are important; however, the currently available methods are limited in their labelling efficiency, specificity and cell permeability. We describe high throughput protein labelling facilitated by minimalistic probes delivered to mammalian cells by microfluidic cell squeezing. High-affinity and target-specific tracing of proteins in various subcellular compartments is demonstrated, culminating in photoinduced labelling within live cells. Both the fine-tuned delivery of subnanomolar concentrations and the minimal size of the probe allow for live-cell super-resolution imaging with very low background and nanometre precision. This method is fast in probe delivery (~ 1,000,000 cells per second), versatile across cell types and can be readily transferred to a multitude of proteins. Moreover, the technique succeeds in combination with well-established methods to gain multiplexed labelling and has demonstrated potential to precisely trace target proteins, in live mammalian cells, by super-resolution microscopy. PMID- 26822410 TI - Mitochondrial Dysfunction may explain symptom variation in Phelan-McDermid Syndrome. AB - Phelan-McDermid Syndrome (PMS), which is defined by a deletion within 22q13, demonstrates significant phenotypic variation. Given that six mitochondrial genes are located within 22q13, including complex I and IV genes, we hypothesize that mitochondrial complex activity abnormalities may explain phenotypic variation in PMS symptoms. Complex I, II, II + III and IV activity was measured in 51 PMS participants. Caretakers completed questionnaires and provided genetic information through the PMS foundation registry. Complex activity was abnormal in 59% of PMS participants. Abnormalities were found in complex I and IV but not complex II + III and II activity, consistent with disruption of genes within the 22q13 region. However, complex activity abnormalities were not related to specific gene deletions suggesting a "neighboring effect" of regional deletions on adjacent gene expression. A specific combination of symptoms (autism spectrum disorder, developmental regression, failure-to-thrive, exercise intolerance/fatigue) was associated with complex activity abnormalities. 64% of 106 individuals in the PMS foundation registry who did not have complex activity measured also endorsed this pattern of symptoms. These data suggest that mitochondrial abnormalities, specifically abnormalities in complex I and IV activity, may explain some phenotypic variation in PMS individuals. These results point to novel pathophysiology mechanisms and treatment targets for PMS patients. PMID- 26822411 TI - Effects of the eta(5)-C5H4(i)Pr Ligand on the Properties Exhibited by Its Tungsten Nitrosyl Complexes. AB - Reaction of Na[eta(5)-C5H4(i)Pr] with W(CO)6 in refluxing THF for 4 days generates a solution of Na[(eta(5)-C5H4(i)Pr)W(CO)3] that when treated with N methyl-N-nitroso-p-toluenesulfonamide at ambient temperatures affords (eta(5) C5H4(i)Pr)W(NO)(CO)2 (1) that is isolable in good yield as an analytically pure orange oil. Treatment of 1 with an equimolar amount of I2 in Et2O at ambient temperatures affords (eta(5)-C5H4(i)Pr)W(NO)I2 (2) as a dark brown solid in excellent yield. Sequential treatment at low temperatures of 2 with 0.5 equiv of Mg(CH2CMe3)2 and Mg(CH2CH?CMe2)2 in Et2O produces the alkyl allyl complex, (eta(5)-C5H4(i)Pr)W(NO)(CH2CMe3)(eta(3)-CH2CHCMe2) (3), as a thermally sensitive yellow liquid. Complex 3 may also be synthesized, albeit in low yield, in one vessel at low temperatures by reacting 1 first with 1 equiv of PCl5 and then with the binary magnesium reagents specified above. Interestingly, similar treatment of 1 in Et2O with PCl5 and only 0.5 equiv of Mg(CH2CH?CMe2)2 results in the formation of the unusual complex (eta(5)-C5H4(i)Pr)W(NO)(PCl2CMe2CH?CH2)Cl2 (4), which probably is formed via a metathesis reaction of the binary magnesium reagent with (eta(5)-C5H4(i)Pr)W(NO)(PCl3)Cl2. The C-D activation of C6D6 by complex 3 has been investigated and compared to that exhibited by its eta(5) C5Me5, eta(5)-C5Me4H, and eta(5)-C5Me4(n)Pr analogues. Kinetic analyses of the various activations have established that the presence of the eta(5)-C5H4(i)Pr ligand significantly increases the rate of the reaction, an outcome that can be attributed to a combination of steric and electronic factors. In addition, mechanistic studies have established that in solution 3 loses neopentane under ambient conditions to generate exclusively the 16e eta(2)-diene intermediate complex (eta(5)-C5H4(i)Pr)W(NO)(eta(2)-CH2?CMeCH?CH2), which then effects the subsequent C-D activations. This behavior contrasts with that exhibited by the eta(5)-C5Me5 analogue of 3 which forms both eta(2)-diene and eta(2)-allene intermediates upon thermolysis. Sixteen-electron (eta(5)-C5H4(i)Pr)W(NO)(eta(2) CH2?CMeCH?CH2) has been isolated as its 18e PMe3 adduct. All new organometallic complexes have been characterized by conventional spectroscopic and analytical methods, and the solid-state molecular structures of two of them have been established by single-crystal X-ray crystallographic analyses. PMID- 26822412 TI - Inhibitory Effects of Retinol Are Greater than Retinoic Acid on the Growth and Adhesion of Human Refractory Cancer Cells. AB - Vitamin A constituents include retinal, which plays a role in vision, and retinoic acid (RA), which has been used in the therapy of human acute promyelocytic leukemia. However, the effects on cancer of retinol (Rol) and its ester, retinyl palmitate (RP) are not known well. In the current study, we examined the effects of these agents on proliferation and adhesion of various cancer cells. Rol exhibited dose-dependent inhibition of the proliferation of human refractory and prostate cancer cells, while RA and RP showed little or no effect. In contrast, RA inhibited the growth of human breast cancer cells to a greater extent than Rol at low concentrations, but not at high concentrations. Rol suppressed adhesion of refractory and prostate cancer cells to a greater extent than RA, while it suppressed adhesion of breast cancer cells as well as RA and of JHP-1 cells less effectively than RA. These results indicate that Rol is a potent suppressor of cancer cell growth and adhesion, which are both linked to metastasis and tumor progression. Rol might be useful for the clinical treatment of cancer. PMID- 26822413 TI - Abstract numerical discrimination learning in rats. AB - In this study, we examined rats' discrimination learning of the numerical ordering positions of objects. In Experiments 1 and 2, five out of seven rats successfully learned to respond to the third of six identical objects in a row and showed reliable transfer of this discrimination to novel stimuli after being trained with three different training stimuli. In Experiment 3, the three rats from Experiment 2 continued to be trained to respond to the third object in an object array, which included an odd object that needed to be excluded when identifying the target third object. All three rats acquired this selective counting task of specific stimuli, and two rats showed reliable transfer of this selective-counting performance to test sets of novel stimuli. In Experiment 4, the three rats from Experiment 3 quickly learned to respond to the third stimulus in object rows consisting of either six identical or six different objects. These results offer strong evidence for abstract numerical discrimination learning in rats. PMID- 26822415 TI - More reasons why Dutch GPs are happier. PMID- 26822414 TI - A null mutation in ANGPTL8 does not associate with either plasma glucose or type 2 diabetes in humans. AB - BACKGROUND: Experiments in mice initially suggested a role for the protein angiopoietin-like 8 (ANGPTL8) in glucose homeostasis. However, subsequent experiments in model systems have challenged this proposed role. We sought to better understand the importance of ANGPTL8 in human glucose homeostasis by examining the association of a null mutation in ANGPTL8 with fasting glucose levels and risk for type 2 diabetes. METHODS: A naturally-occurring null mutation in human ANGPTL8 (rs145464906; c.361C > T; p.Q121X) is carried by ~1 in 1000 individuals of European ancestry and is associated with higher levels of plasma high-density lipoprotein cholesterol, suggesting that this mutation has functional significance. We examined the association of p.Q121X with fasting glucose levels and risk for type 2 diabetes in up to 95,558 individuals (14,824 type 2 diabetics and 80,734 controls). RESULTS: We found no significant association of p.Q121X with either fasting glucose or type 2 diabetes (p-value = 0.90 and 0.65, respectively). Given our sample sizes, we had >98 % power to detect at least a 0.23 mmol/L effect on plasma glucose and >95 % power to detect a 70 % increase in risk for type 2 diabetes. CONCLUSION: Disruption of ANGPTL8 function in humans does not seem to have a large effect on measures of glucose tolerance. PMID- 26822416 TI - The Effects of Letter Design Features and Aging on Legibility. AB - We examined how letter legibility is affected by letter design features (size, contrast, font-type, and complexity), and how this changes with age (by comparing younger [N = 54] and older participants [N = 54]). Types of letters in the study were Japanese characters, Latin alphabets, and digits. Participants verbally reported the letter presented on a Cathode Ray Tube (CRT) display in natural viewing conditions. The legible-contrast threshold was calculated as the contrast boundary of 50% correct answer. We found that letter complexity (i.e., number of strokes) did not affect legible contrast threshold, except for small (<0.35 degrees ) letters. Moreover, letter size even affected the threshold with a function similar but not identical to contrast sensitivity function. This supports the previous hypothesis proposed by Majaj et al. that optimal spatial frequency band exists for letter identification and shifts with its size. Another novel finding was the effect of aging on the legible-contrast threshold and how it related to other letter features. Constant aging effect on legible-contrast was found across letter sizes. Among older adults, the legible-contrast thresholds were 1.2 to 2 times those of younger adults. Moreover, the aging effects were greater for positive-contrast than for negative. PMID- 26822417 TI - Apathy is associated with poor prognosis in amyotrophic lateral sclerosis. AB - BACKGROUND AND PURPOSE: Apathy is the most commonly reported behavioural change in amyotrophic lateral sclerosis (ALS). However, the degree to which it affects prognosis and overlaps with depression in this population is unknown. The present study examined the relationship between level of apathy, mortality and survival time and whether apathy was linked to specific symptom clusters of depression. METHODS: A cohort of 76 consecutive ALS patients attending specialized multidisciplinary clinics were classified according to level of apathy. The effects of clinical factors and apathy on survival time were analysed using univariate and multivariate methods. RESULTS: The majority of patients with moderate to severe apathy died during the study (P = 0.003) and had a median survival time of 21.7 months, considerably shorter than patients with mild apathy (46.9 months) and no apathy (51.9 months) (P = 0.0001). Apathy remained a significant predictor of survival even after controlling for clinical factors and symptom duration at the time of study entry (hazard ratio 3.8, 95% confidence interval 1.9-7.5, P = 0.0001). Depression with demoralization was not associated with level of apathy (P = 0.172) whereas depression with anhedonia was more common in patients with apathy than in those without apathy (P = 0.006). CONCLUSIONS: The presence of severe apathy is an independent, negative prognostic factor in ALS. PMID- 26822419 TI - EYE LENS EXPOSURE TO MEDICAL STAFF PERFORMING ELECTROPHYSIOLOGY PROCEDURES: DOSE ASSESSMENT AND CORRELATION TO PATIENT DOSE. AB - The purpose of this study was to assess the patient exposure and staff eye dose levels during implantation procedures for all types of pacemaker therapy devices performed under fluoroscopic guidance and to investigate potential correlation between patients and staff dose levels. The mean eye dose during pacemaker/defibrillator implementation was 12 uSv for the first operator, 8.7 uSv for the second operator/nurse and 0.50 uSv for radiographer. Corresponding values for cardiac resynchronisation therapy procedures were 30, 26 and 2.0 uSv, respectively. Significant (p < 0.01) correlation between the eye dose and the kerma-area product was found for the first operator and radiographers, but not for other staff categories. The study revealed eye dose per procedure and eye dose normalised to patient dose indices for different staff categories and provided an input for radiation protection in electrophysiology procedures. PMID- 26822420 TI - THE CONVERSION OF EXPOSURES DUE TO RADON INTO THE EFFECTIVE DOSE TAKING INTO ACCOUNT THE EQUIVALENCE OF RISKS FROM SHORT- AND LONG-TERM EXPOSURES. AB - The theoretical basis for comparing risks from short- and long-term exposures is developed aiming at implementing long-term exposures into a unique and consistent system of radiation protection. Based on system-analytical considerations, the equivalence of population-averaged risk rates due to prolonged exposures and population-averaged lifetime risks due to short-term exposures is shown. The consequences of this risk analysis are discussed, focussing on long-term exposures due to residential radon. Equations for the dose conversion of exposures due to radon into the effective dose are derived. PMID- 26822421 TI - VIEWDEX: A STATUS REPORT. AB - ViewDEX (Viewer for Digital Evaluation of X-ray images) is an image viewer and task manager suitable for research and optimisation tasks in medical imaging. The software has undergone continuous development during more than a decade and has during this time period been used in numerous studies. ViewDEX is DICOM compatible, and the features of the interface (tasks, image handling and functionality) are general and flexible. The set-up of a study is determined by altering properties in a text-editable file, enabling easy and flexible configuration. ViewDEX is developed in Java and can run from any disc area connected to a computer. It is free to use for non-commercial purposes and can be downloaded from http://www.vgregion.se/sas/viewdex The purposes of the present article are to give a short overview of the development of ViewDEX and to describe recent updates of the software. In addition, a description on how to configure a viewing session in ViewDEX is provided. PMID- 26822418 TI - Stroke Treatment Associated with Rehabilitation Therapy and Transcranial DC Stimulation (START-tDCS): a study protocol for a randomized controlled trial. AB - BACKGROUND: Traditional treatment for motor impairment after stroke includes medication and physical rehabilitation. The transcranial direct current stimulation associated with a standard physical therapy program may be an effective therapeutic alternative for these patients. METHODS: This study is a sham-controlled, double-blind, randomized clinical trial aiming to evaluate the efficacy of transcranial direct current stimulation in activities of daily living and motor function post subacute stroke. In total there will be 40 patients enrolled, diagnosed with subacute, ischemic, unilateral, non-recurring stroke. Participants will be randomized to two groups, one with active stimulation and the other with a placebo current. Patients and investigators will be blinded. Everyone will receive systematic physical therapy, based on constraint-induced movement therapy. The intervention will be applied for 10 consecutive days. Patients will undergo three functional assessments: at baseline, week 2, and week 4. Neuropsychological tests will be performed at baseline and week 4. Adverse effects will be computed at each session. On completion of the baseline measures, randomization will be conducted using random permuted blocks. The randomization will be concealed until group allocation. DISCUSSION: This study will investigate the combined effects of transcranial direct current stimulation and physical therapy on functional improvement after stroke. We tested whether the combination of these treatments is more effective than physical therapy alone when administered in the early stages after stroke. TRIAL REGISTRATION: NCT02156635-- May 30, 2014. Randomization is ongoing (40 participants randomized as of the end of December 2015). PMID- 26822422 TI - AN INVESTIGATION INTO CT RADIATION DOSE VARIATIONS FOR HEAD EXAMINATIONS ON MATCHED EQUIPMENT. AB - This study investigated radiation dose and image quality differences for computed tomography (CT) head examinations across centres with matched CT equipment. Radiation dose records and imaging protocols currently employed across three European university teaching hospitals were collated, compared and coded as Centres A, B and C from specification matched CT equipment models. Patient scans (n = 40) obtained from Centres A and C were evaluated for image quality, based on the visualisation of Commission of European Community (CEC) image quality criteria using visual grading characteristic (VGC) analysis, where American Board of Radiology examiners (n = 11) stated their confidence in identifying anatomical criteria. Mean doses in terms of CT dose index (CTDIvol-mGy) and dose length product (DLP-mGy cm) were as follows: Centre A-33.12 mGy and 461.45 mGy cm; Centre B -101 mGy (base)/32 mGy (cerebrum) and 762 mGy cm and Centre C-71.98 mGy and 1047.26 mGy cm, showing a significant difference (p <= 0.05) in DLP across centres. VGC analysis indicated better visualisation of CEC criteria on Centre C images (VGCAUC 0.225). All three imaging protocols are routinely used clinically, and image quality is acceptable in each centre. Clinical centres with identical model CT scanners have variously customised their protocols achieving a range of dose savings and still resulting in clinically acceptable image quality. PMID- 26822423 TI - TESTING THE IDEAS GUIDELINES AS APPLIED TO PLUTONIUM INTAKES. AB - The IDEAS Guidelines [Doerfel, H., et al General Guidelines for the Estimation of Committed Effective Dose from Incorporation Monitoring Data. Report FZKA 7243, Forschungszentrum Karlsruhe, GmbH (2006); Castellani, C. M., Marsh, J. W., Hurtgen, C., Blanchardon, E., Berard, P., Giusani, A. and Lopez, M. A. IDEAS Guidelines (Version 2) for the Estimation of Committed Doses from Incorporation Monitoring Data. EURADOS Report 2013-01, Braunschweig (2013)] provide a structured approach to the assessment of intakes of radionuclides. In order to check that the guidelines, when applied to typical monitoring programmes, lead to reliable assessments, a number of numerically-generated datasets have been constructed and assessed using the guidelines. The dose and intake obtained by the assessment can be compared with the 'true' dose and intake. In this way, the accuracy of the IDEAS assessment process can be examined when applied to monitoring programmes that are typically used in the nuclear industry. The simulations focus on assessments carried out as a result of elevated (239)Pu activities in routine urine samples, which lead to follow-up urine and faecal samples being provided. Cases where the assessor makes the correct initial assumption about lung solubility can be compared with cases where this initial choice is wrong. The results of these simulations and the implication for the use of monitoring programmes are discussed. PMID- 26822424 TI - EYE LENS DOSES IN NUCLEAR MEDICINE: A MULTICENTRIC STUDY IN BELGIUM AND POLAND. AB - This study aimed to investigate the level of the eye lens (EL) doses in nuclear medicine in the light of the new International Commission on Radiological Protection limit. In 7 Belgian and 1 Polish hospitals, 45 staff members were monitored for EL (Hp(3)) and whole-body (WB) (Hp(10)) doses using dedicated dosemeters. Weekly measurements were carried out and used to estimate annual doses. Mostly diagnostic procedures involving radionuclides such as (99m)Tc and (18)F were monitored; measurements were also performed for therapeutic procedures. The cumulative doses showed important variation across the participants. The weekly EL and WB doses ranged from 0.02 to 0.27 and 0.03 to 0.17 mSv, respectively; the annual EL and WB doses ranged from 0.6 to 9.3 and 0.9 to 8.0 mSv, respectively. Some correlation was found between the EL and the WB doses. No significant correlation with the manipulated activities was found. PMID- 26822425 TI - Limited public ability to recognise and understand the universal sign for automated external defibrillators. AB - OBJECTIVE: To study if the public is able to recognise and understand the International Liaison Committee on Resuscitation (ILCOR) sign for automated external defibrillators (AEDs), and to explore how national resuscitation councils have adopted the sign. METHODS: A survey was conducted among travellers in an international airport serving 21 million passengers annually. Participants were asked to state the meaning of six international safety signs, one of which was the ILCOR AED sign. Also, all national resuscitation councils forming ILCOR were contacted to determine whether they recommend the ILCOR AED sign and the existence of national legislation regarding AED signage. RESULTS: In total, 493 travellers (42 nationalities) were included. Correct identification of the ILCOR AED sign was achieved by 39% (95% CI 35% to 43%). Information on AED signage was obtained from 41 of 44 (93%) national resuscitation councils; 26 councils (63%) recommended the use of the ILCOR AED sign. In two countries, the ILCOR AED sign was mandatory by law. CONCLUSIONS: There is limited public recognition and understanding of the ILCOR AED sign. The ILCOR AED sign is not unanimously recommended by national resuscitation councils worldwide. Initiatives promoting public awareness of AEDs are warranted. PMID- 26822426 TI - The spectrum of low-output low-gradient aortic stenosis with normal ejection fraction. AB - Low-flow, low-gradient (LF/LG) severe aortic stenosis (AS) with preserved ejection fraction refers to the condition of AS with aortic valve area <=1 cm(2), stroke volume index <35 mL/m(2), mean aortic valve gradient <40 mm Hg and left ventricular ejection fraction >=50%. This mismatch of aortic valve area suggesting severe stenosis and 'low' gradient in some patients has led to confusion as to the severity of stenosis. Conditions previously labelled as LF/LG severe AS include a spectrum, with measurement error probably being the most common cause of marked inconsistency between gradient, valve area and patient presentation. The presence of LG severe AS may be overestimated in petite patients, who may have aortic valve area slightly less than 1 cm(2)with only moderate AS. Concomitant cardiac conditions besides AS, including significant mitral and tricuspid regurgitation, intracardiac shunts and constrictive pericarditis, may contribute to reduced stroke volume, and evidence for these must be sought at the time of echocardiography. True LF/LG severe AS is associated with a unique and probably maladaptive remodelling pattern with smaller ventricles, increasing relative wall thickness, progressive worsening of diastolic function and higher afterload, as demonstrated by lower systemic arterial compliance, higher systemic vascular resistance and higher valvuloarterial impedance. Control of hypertension is essential to the appropriate management of patients with AS. Aortic valve replacement should be considered in patients with compelling evidence of severe AS who remain symptomatic despite optimal treatment of hypertension. PMID- 26822428 TI - Hepcidin as a new biomarker for detecting autologous blood transfusion. AB - Autologous blood transfusion (ABT) is an efficient way to increase sport performance. It is also the most challenging doping method to detect. At present, individual follow-up of haematological variables via the athlete biological passport (ABP) is used to detect it. Quantification of a novel hepatic peptide called hepcidin may be a new alternative to detect ABT. In this prospective clinical trial, healthy subjects received a saline injection for the control phase, after which they donated blood that was stored and then transfused 36 days later. The impact of ABT on hepcidin as well as haematological parameters, iron metabolism, and inflammation markers was investigated. Blood transfusion had a particularly marked effect on hepcidin concentrations compared to the other biomarkers, which included haematological variables. Hepcidin concentrations increased significantly: 12 hr and 1 day after blood reinfusion, these concentrations rose by seven- and fourfold, respectively. No significant change was observed in the control phase. Hepcidin quantification is a cost-effective strategy that could be used in an "ironomics" strategy to improve the detection of ABT. PMID- 26822427 TI - Long-term cardiac monitoring in older adults with unexplained falls and syncope. AB - AIMS: Unexplained falls account for 20% of falls in older cohorts. The role of the implantable loop recorder (ILR) in the detection of arrhythmias in patients with unexplained falls is unknown. We aimed to examine the diagnostic utility of the ILR in detection of arrhythmogenic causes of unexplained falls in older patients. METHODS: A single centre, prospective, observational cohort study of recurrent fallers over the age of 50 years with two or more unexplained falls presenting to an emergency department. Insertion of an ILR (Reveal, Medtronic, Minnesota, USA) was used to detect arrhythmia. The primary outcome was detection of cardiac arrhythmia associated with a fall or syncope. The secondary outcome was detection of cardiac arrhythmia independent of falls or syncope, and falls or syncope without associated arrhythmia. RESULTS: Seventy patients, mean age 70 years (51-85 years) received an ILR. In 70% of patients cardiac arrhythmias were detected at a mean time of 47.3 days (SD 48.25). In 20%, falls were attributable to a modifiable cardiac arrhythmia; 10 (14%) received a cardiac pacemaker, 4 (6%) had treatment for supraventricular tachycardia. Patients who had a cardiac arrhythmia detected were more likely to experience a further fall. CONCLUSIONS: 14 (20%) patients demonstrated an arrhythmia which was attributable as the cause of their fall. Patients who have cardiac arrhythmia are significantly more likely to experience future falls. Further research is important to investigate if early detection of arrhythmogenic causes of falls using the ILR prevents future falls in older patients. PMID- 26822429 TI - A metasurface carpet cloak for electromagnetic, acoustic and water waves. AB - We propose a single low-profile skin metasurface carpet cloak to hide objects with arbitrary shape and size under three different waves, i.e., electromagnetic (EM) waves, acoustic waves and water waves. We first present a metasurface which can control the local reflection phase of these three waves. By taking advantage of this metasurface, we then design a metasurface carpet cloak which provides an additional phase to compensate the phase distortion introduced by a bump, thus restoring the reflection waves as if the incident waves impinge onto a flat mirror. The finite element simulation results demonstrate that an object can be hidden under these three kinds of waves with a single metasurface cloak. PMID- 26822430 TI - Establishment and characterization of a novel cell line from the brain of golden pompano (Trachinotus ovatus). AB - Golden pompano is a commercially important marine fish that is widely cultured in China, Japan, and Southeast Asian countries but has been seriously threatened by pathogen. A novel cell line (TOGB) derived from the brain of golden pompano Trachinotus ovatus was established and characterized in this study. TOGB cell line showed high virus susceptibility, especially grouper nervous necrosis virus (GNNV) and Singapore grouper iridovirus (SGIV). As one of the most devastating viruses in marine fish aquaculture, nervous necrosis virus (NNV) causes high mortality rates exceeding 95% in severe outbreaks. Then, TOGB cell line was a useful tool for propagating viruses and provides a potentially valuable resource for the study of viral pathogenesis, the development of antiviral strategies. The TOGB cell lines showed potential application in environmental monitoring. The extracellular products from Vibrio anguillarum and Vibrio alginolyticus demonstrated cytotoxic effects in TOGB cells. TOGB cells grew most rapidly at 28 degrees C, with an optimal concentration of 10% fetal bovine serum in L-15 medium. TOGB cells were diploid (2N = 54). The transfection efficiencies of TOGB cells were 8.6% at the 15th passage and 64.8% at the 45th passage, indicating that the cells are suitable for foreign gene expression. PMID- 26822431 TI - The synergistic effect of 5Azadc and TSA on maintenance of pluripotency of chicken ESCs by overexpression of NANOG gene. AB - NANOG is a transcription factor that functions in embryonic stem cells (ESCs) and a key factor in maintaining pluripotency. Here, we cloned the NANOG gene promoter from the Rugao yellow chicken and constructed a dual luciferase reporter vector to detect its transcriptional activity and analyze the effects of 5-aza-2' deoxycytidine (5-Azadc) and trichostatin A (TSA) on NANOG promoter activity and ESC pluripotency maintenance in vitro. NANOG transcriptional activity was enhanced when 5-Azadc and TSA were used alone or together, suggesting the possibility of elevated methylation of the CpG island in the NANOG regulatory region. When ESCs were cultured in basic medium with 5-Azadc and TSA in vitro, significantly more cell colonies were maintained in the 5-Azadc + TSA group than in the control group, which had many differentiated cells and few cell colonies after 6 d of induction. On the tenth day of induction, the cells in the control group fully differentiated and no cell colonies remained, but many cell colonies were present in the 5-Azadc + TSA group. The expression of NANOG in the cell colonies was confirmed by indirect immunofluorescence. Furthermore, ESCs could be passaged to the 12th generation under 5-Azadc and TSA treatment and maintained their pluripotency. Thus, we showed that 5-Azadc and TSA can effectively maintain chicken ESC pluripotency in vitro by increasing NANOG gene expression. PMID- 26822432 TI - MiR-221-inhibited adipose tissue-derived mesenchymal stem cells bioengineered in a nano-hydroxy apatite scaffold. AB - The repair of skeletal defects is the main goal of bone tissue engineering. Recent literature highlighted various regulatory roles of microRNAs in stem cell fate determination. In addition, the role of porous hydroxyapatite/polycaprolacton (nHA/PCL) as a bioactive scaffold which enhances adipose tissue-derived mesenchymal stem cells (AT-MSCs) growth and osteogenic differentiation has been proved. The aim of the present study was to investigate the synergistic potential of both down-regulating miR-221 and nHA/PCL scaffold seeding in osteogenic potential of AT-MSCs. After isolation and characterization of AT-MSCs, the transfection of anti-miR-221 was performed into the cells using lipofectamine 2000 and the transfected cells were seeded into a synthesized nHA/PCL scaffold. The DAPI staining confirmed the presence of AT-MSCs on nHA/PCL scaffold. Quantitative expression of osteoblast marker genes, Runx2, and osteocalcin of the transfected cells in the scaffold were evaluated. Interestingly, significant upregulation of transcribed Runx2 and osteocalcin genes (P < 0.01) were observed in miR-221-inhibited nHA/PCL seeded cells. Also, alkaline phosphatase activity (ALP) was significantly higher (P < 0.01) in miR 221-inhibited AT-MSCs seeded on nHA/PCL than those seeded on nHA/PCL or transfected with anti-miR-221, individually. The results of this combination suggest a valuable method for enhancing osteogenesis in AT-MSCs. This method could be applicable for gene-cell therapy of bone defects. PMID- 26822433 TI - MicroRNA-29 regulates high-glucose-induced apoptosis in human retinal pigment epithelial cells through PTEN. AB - Hyperglycemia or high-glucose (HG)-induced apoptosis in human retinal pigment epithelial (RPE) cells is a characteristic process in diabetic retinopathy. In our study, we examined whether microRNA-29 (miR-29) may regulate HG-induced RPE cell apoptosis. Human RPE cell line, ARPE-19 cells, was treated with various high concentration of glucose in vitro. HG-induced RPE cell apoptosis was examined by terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay and miR-29 gene expression by quantitative RT-PCR (qRT-PCR). miR-29 was then downregulated in RPE cells, and its effect on HG-induced apoptosis was examined by TUNEL assay and western blot assay on caspase-7 protein. Association of miR-29 on its downstream target, PTEN, in HG-induced RPE cell apoptosis was evaluated by dual-luciferase assay and qRT-PCR. PTEN was silenced in RPE cells. The effects of PTEN downregulation on miR-29-mediated HG-induced RPE cell apoptosis were also examined by TUNEL and western blot assays. HG induced significant apoptosis in RPE cells in a dose-dependent manner. miR-29 was upregulated by HG in RPE cells. miR-29 downregulation protected HG-induced apoptosis and reduced the production of caspase-7 protein in RPE cells. PTEN was shown to be directly downregulated by HG and then upregulated by miR-29 downregulation in RPE cells. Small interfering RNA (siRNA)-mediated PTEN downregulation reversed the protective effect of miR-29 downregulation on HG induced RPE cell apoptosis. This study demonstrates that miR-29, through inverse association of PTEN, plays an important role in the process of HG-induced apoptosis in RPE cells. PMID- 26822434 TI - IGF-I induces adipose derived mesenchymal cell chondrogenic differentiation in vitro and enhances chondrogenesis in vivo. AB - Recent studies have demonstrated that insulin-like growth factor-1 (IGF-I) modulates bone mesenchymal stem cell chondrogenic differentiation independent of transforming growth factor beta (TGF-beta) signaling in vitro. However, it is unclear whether IGF-I can solely modulate human adipose-derived mesenchymal cell (hAMC) chondrogenic differentiation, or whether it has additive effects with TGF beta1 to induce chondrogenic differentiation in vitro and development of mature cartilage in vivo. We investigated the effect of IGF-I on the induction of hAMC chondrogenic differentiation in the presence or absence of transforming growth factor beta 1 (TGF-beta1) in vitro, and chondrogenesis of the induced hAMC in vivo. The results showed that IGF-I alone induced collagen type II, aggrecan, and Sox9 mRNA expression and collagen type II and aggrecan proteins expressions in hAMCs. Notably, there was greater mRNA expression of collagen type II, aggrecan and Sox9, and greater protein expression of collagen type II and aggrecan following TGF-beta1 + IGF-I treatment, compared to either TGF-beta1 or IGF-I treated hAMCs. These results were confirmed in cartilage tissues derived from induced hAMCs. These findings indicate that IGF-I alone has the ability to induce chondrogenic differentiation and has additive effects with TGF-beta1 to induce chondrogenic differentiation in vitro and in vivo. PMID- 26822435 TI - EEG oscillatory patterns and classification of sequential compound limb motor imagery. AB - BACKGROUND: A number of studies have been done on movement imagination of motor sequences with a single limb. However, brain oscillatory patterns induced by movement imagination of motor sequences involving multiple limbs have not been reported in recent years. The goal of the present study was to verify the feasibility of application of motor sequences involving multiple limbs to brain computer interface (BCI) systems based on motor imagery (MI). The changes of EEG patterns and the inter-influence between movements associated with the imagination of motor sequences were also investigated. METHODS: The experiment, where 12 healthy subjects participated, involved one motor sequence with a single limb and three kinds of motor sequences with two or three limbs. The activity involved mental simulation, imagining playing drums with two conditions (60 and 30 beats per minute for the first and second conditions, respectively). RESULTS: Movement imagination of different limbs in the sequence contributed to time variant event-related desynchronization (ERD) patterns within both mu and beta rhythms, which was more obvious for the second condition compared with the first condition. The ERD values of left/right hand imagery with prior hand imagery were significantly larger than those with prior foot imagery, while the phase locking values (PLVs) between central electrodes and the mesial frontocentral electrode of non-initial movement were significantly larger than those of the initial movement during imagination of motor sequences for both conditions. Classification results showed that the power spectral density (PSD) based method outperformed the multi-class common spatial patterns (multi-CSP) based method: The highest accuracies were 82.86 % and 91.43 %, and the mean values were 65 % and 74.14 % for the first and second conditions, respectively. CONCLUSIONS: This work implies that motor sequences involving multiple limbs can be utilized to build a multimodal classification paradigm in MI-based BCI systems, and that prior movement imagination can result in the changes of neural activities in motor areas during subsequent movement imagination in the process of limb switching. PMID- 26822437 TI - Differences in physical aging measured by walking speed: evidence from the English Longitudinal Study of Ageing. AB - BACKGROUND: Physical functioning and mobility of older populations are of increasing interest when populations are aging. Lower body functioning such as walking is a fundamental part of many actions in daily life. Limitations in mobility threaten independent living as well as quality of life in old age. In this study we examine differences in physical aging and convert those differences into the everyday measure of single years of age. METHODS: We use the English Longitudinal Study of Ageing, which was collected biennially between 2002 and 2012. Data on physical performance, health as well as information on economics and demographics of participants were collected. Lower body performance was assessed with two timed walks at normal pace each of 8 ft (2.4 m) of survey participants aged at least 60 years. We employed growth curve models to study differences in physical aging and followed the characteristic-based age approach to illustrate those differences in single years of age. RESULTS: First, we examined walking speed of about 11,700 English individuals, and identified differences in aging trajectories by sex and other characteristics (e.g. education, occupation, regional wealth). Interestingly, higher educated and non manual workers outperformed their counterparts for both men and women. Moreover, we transformed the differences between subpopulations into single years of age to demonstrate the magnitude of those gaps, which appear particularly high at early older ages. CONCLUSIONS: This paper expands research on aging and physical performance. In conclusion, higher education provides an advantage in walking of up to 15 years for men and 10 years for women. Thus, enhancements in higher education have the potential to ensure better mobility and independent living in old age for a longer period. PMID- 26822438 TI - New Brunswick nurses' views on nursing research, and factors influencing their research activities in clinical practice. AB - New Brunswick became the first province in Canada to require a baccalaureate degree in nursing as the entry to practice, yet nursing research in hospital settings remains quite low. This study examined clinical nurses' views on nursing research, and identified some contributing factors to the research-practice gap. This descriptive, cross-sectional multicenter study involved 1081 nurses working in the Francophone Regional Health Authority in New Brunswick, Canada. Nurses were eager to identify nursing-care problems to improve patient care (92.9%), and to be involved in collecting data for nursing research studies (95.2%). However, without research supervision, few had engaged in basic research activities, such as formulating or refining research questions (24.5%), presenting at research conferences (6.9%), or changing their practice based on research findings (27.2%). Younger, more educated nurses, nurse managers, and educators participated more readily in research. Sharing research and clinical expertise, as well as infrastructures between academic and clinical institutions is the key to enduring successful patient-centered nursing research in clinical settings. Concrete actions are proposed to build clinical nursing research. PMID- 26822436 TI - Phylogenetic, virulence and antibiotic resistance characteristics of commensal strain populations of Escherichia coli from community subjects in the Paris area in 2010 and evolution over 30 years. AB - It is important to study commensal populations of Escherichia coli because they appear to be the reservoir of both extra-intestinal pathogenic E. coli and antibiotic resistant strains of E. coli. We studied 279 dominant faecal strains of E. coli from 243 adults living in the community in the Paris area in 2010. The phylogenetic group and subgroup [sequence type complex (STc)] of the isolates and the presence of 20 virulence genes were determined by PCR assays. The O-types and resistance to 18 antibiotics were assessed phenotypically. The B2 group was the most frequently recovered (34.0 %), followed by the A group (28.7 %), and other groups were more rare. The most prevalent B2 subgroups were II (STc73), IV (STc141), IX (STc95) and I (STc131), with 22.1, 21.1, 16.8 and 13.7 %, respectively, of the B2 group strains. Virulence factors (VFs) were more common in B2 group than other strains. One or more resistances were found in 125 strains (44.8 % of the collection) but only six (2.2 % of the collection) were multiresistant; no extended-spectrum beta-lactamase-producing strain was isolated. The C phylogroup and clonal group A strains were the most resistant. No trade-off between virulence and resistance was evidenced. We compared these strains with collections of strains gathered under the same conditions 30 and 10 years ago. There has been a parallel and linked increase in the frequency of B2 group strains (from 9.4 % in 1980, to 22.7 % in 2000 and 34.0 % in 2010) and of VFs. Antibiotic resistance also increased, from 22.6 % of strains resistant to at least one antibiotic in 1980, to 31.8 % in 2000 and 44.8 % in 2010; resistance to streptomycin, however, remained stable. Commensal human E. coli populations have clearly evolved substantially over time, presumably reflecting changes in human practices, and particularly increasing antibiotic use. PMID- 26822439 TI - We've Come a Long Way, Baby (But We're Not There Yet): Gender Past, Present, and Future. AB - Gender has long been, and continues to be, a powerful predictor of developmental experiences and outcomes. Observations drawn from personal history, developmental science, and life beyond the academy show that historically, gender constraints have diminished in some ways, but remain robust in others. Reviewed are children's constructive processes that--in interaction with the embedding ecology -foster the emergence and persistence of gendered phenomena. Reviews of interventions designed to increase girls' science participation demonstrate the need to evaluate both intended and unintended program consequences. Discussion of the single-sex schooling debate shows the importance of foundational conceptualizations of gender, and illuminates research-to-policy processes. After identifying newly emerging gender conceptualizations, the concluding section highlights the need to consider how gender conceptualizations do and should affect science and society. PMID- 26822440 TI - Introduction to the Special Section on Epigenetics. AB - Epigenetics provides the opportunity to revolutionize our understanding of the role of genetics and the environment in explaining human behavior, although the use of epigenetics to study human behavior is just beginning. In this introduction, the authors present the basics of epigenetics in a way that is designed to make this exciting field accessible to a wide readership. The authors describe the history of human behavioral epigenetic research in the context of other disciplines and graphically illustrate the burgeoning of research in the application of epigenetic methods and principles to the study of human behavior. The role of epigenetics in normal embryonic development and the influence of biological and environmental factors altering behavior through epigenetic mechanisms and developmental programming are discussed. Some basic approaches to the study of epigenetics are reviewed. The authors conclude with a discussion of challenges and opportunities, including intervention, as the field of human behavioral epigenetics continue to grow. PMID- 26822441 TI - Serotonin Transporter Gene (SLC6A4) Methylation Associates With Neonatal Intensive Care Unit Stay and 3-Month-Old Temperament in Preterm Infants. AB - Preterm birth and Neonatal Intensive Care Unit (NICU) stay are early adverse stressful experiences, which may result in an altered temperamental profile. The serotonin transporter gene (SLC6A4), which has been linked to infant temperament, is susceptible to epigenetic regulation associated with early stressful experience. This study examined a moderation model in which the exposure to NICU related stress and SLC6A4 methylation moderated infant temperament at 3 months of age. SLC6A4 methylation at 20 CpG sites was quantified in preterm infants (N = 48) and full-term infants (N = 30) from Italian middle-class families. Results suggested that in preterm infants NICU-related stress might be associated with alterations of serotonergic tone as a consequence of SLC6A4 methylation, which in turn, might associate with temperamental difficulties assessed at 3 months of age. PMID- 26822442 TI - Epigenetic Regulation of Placental NR3C1: Mechanism Underlying Prenatal Programming of Infant Neurobehavior by Maternal Smoking? AB - Epigenetic regulation of the placental glucocorticoid receptor gene (NR3C1) was investigated as a mechanism underlying links between maternal smoking during pregnancy (MSDP) and infant neurobehavior in 45 mother-infant pairs (49% MSDP exposed; 52% minorities; ages 18-35). The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale was administered 7 times over the 1st postnatal month; methylation of placental NR3C1 was assessed via bisulfite pyrosequencing. Increased placental NR3C1 methylation was associated with increased infant attention and self-regulation, and decreased lethargy and need for examiner soothing over the 1st postnatal month. A causal steps approach revealed that NR3C1 methylation and MSDP were independently associated with lethargic behavior. Although preliminary, results highlight the importance of epigenetic mechanisms in elucidating pathways to neurobehavioral alterations from MSDP. PMID- 26822443 TI - Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic-Pituitary-Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo. AB - Exposure to stress early in life permanently shapes activity of the hypothalamic pituitary-adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight (BW), and HPA axis functioning. Little is known about the biological mechanisms by which prenatal stress affects postnatal functioning. This study addresses this gap by examining the effect of chronic stress and traumatic war-related stress on epigenetic changes in four key genes regulating the HPA axis in neonatal cord blood, placenta, and maternal blood: CRH, CRHBP, NR3C1, and FKBP5. Participants were 24 mother-newborn dyads in the conflict ridden region of the eastern Democratic Republic of Congo. BW data were collected at delivery and maternal interviews were conducted to assess culturally relevant chronic and war-related stressors. Chronic stress and war trauma had widespread effects on HPA axis gene methylation, with significant effects observed at transcription factor binding (TFB) sites in all target genes tested. Some changes in methylation were unique to chronic or war stress, whereas others were observed across both stressor types. Moreover, stress exposures impacted maternal and fetal tissues differently, supporting theoretical models that stress impacts vary according to life phase. Methylation in several NR3C1 and CRH CpG sites, all located at TFB sites, was associated with BW. These findings suggest that prenatal stress exposure impacts development via epigenetic changes in HPA axis genes. PMID- 26822444 TI - The Contributions of Maternal Sensitivity and Maternal Depressive Symptoms to Epigenetic Processes and Neuroendocrine Functioning. AB - This study tested whether maternal responsiveness may buffer the child to the effects of maternal depressive symptoms on DNA methylation of NR3C1, 11beta-HSD2, and neuroendocrine functioning. DNA was derived from buccal epithelial cells and prestress cortisol was obtained from the saliva of 128 infants. Mothers with depressive symptoms who were more responsive and who engaged in more appropriate touch during face-to-face play had infants with less DNA methylation of NR3C1 and 11beta-HSD2 compared to mothers with depressive symptoms who were also insensitive. The combination of exposure to maternal depressive symptoms and maternal sensitivity was related to the highest prestress cortisol levels, whereas exposure to maternal depressive symptoms and maternal insensitivity was related to the lowest prestress cortisol levels. PMID- 26822445 TI - Methylation of the Glucocorticoid Receptor Gene Promoter in Preschoolers: Links With Internalizing Behavior Problems. AB - Accumulating evidence suggests that early adversity is linked to methylation of the glucocorticoid receptor (GR) gene, NR3C1, which is a key regulator of the hypothalamic-pituitary-adrenal axis. Yet no prior work has considered the contribution of methylation of NR3C1 to emerging behavior problems and psychopathology in childhood. This study examined the links between methylation of NR3C1 and behavior problems in preschoolers. Data were drawn from a sample of preschoolers with early adversity (n = 171). Children ranged in age from 3 to 5 years, were racially and ethnically diverse, and nearly all qualified for public assistance. Seventy-one children had child welfare documentation of moderate to severe maltreatment in the past 6 months. Structured record review and interviews in the home were used to assess early adversity. Parents reported on child internalizing and externalizing behavior problems. Methylation of NR3C1 at exons 1D , 1F , and 1H were measured via sodium bisulfite pyrosequencing from saliva DNA. Methylation of NR3C1 at exons 1D and 1F was positively associated with internalizing (r = .21, p < .01 and r = .23, p < .01, respectively), but not externalizing, behavior problems. Furthermore, NR3C1 methylation mediated effects of early adversity on internalizing behavior problems. These results suggest that methylation of NR3C1 contributes to psychopathology in young children, and NR3C1 methylation from saliva DNA is salient to behavioral outcomes. PMID- 26822446 TI - Epigenetic Patterns Modulate the Connection Between Developmental Dynamics of Parenting and Offspring Psychosocial Adjustment. AB - This study attempted to establish and quantify the connections between parenting, offspring psychosocial adjustment, and the epigenome. The participants, 35 African American young adults (19 females and 16 males; age = 17-29.5 years), represented a subsample of a 3-wave longitudinal 15-year study on the developmental trajectories of low-income urban mother-offspring dyads. Mothers were assessed on their perceptions of maternal stress at each wave. Offspring were assessed on their perceptions of maternal parenting at each wave and on their adaptive and maladaptive behavior at the last wave. Genome-wide DNA methylation in peripheral T lymphocytes at the third wave was assayed using Methyl Binding Domain(MBD) sequencing. Statistically significant associations were identified between the change in offspring's perception of parenting from middle childhood to adulthood and the DNA methylation in offspring's adult genomes. Specifically, the slope of perceived parental rejection across the 3 time points was related to an increase in methylation, or a potential downregulation, of 565 genes thought to be involved in the control of a broad spectrum of biological functions generally related to cellular signaling. A subset of these epigenetic marks, clustered in 23 genes, some of which participate in the development and functioning of the CNS, were in turn associated with psychosocial adjustment as captured by interpersonal relationships and emotional self-evaluation. This appears to be one of the first investigations of the modulating role of the methylome in associations between developmental dynamics of parenting throughout the formative years of child and adolescent development and psychosocial adjustment in adulthood. PMID- 26822447 TI - Parenting, Socioeconomic Status Risk, and Later Young Adult Health: Exploration of Opposing Indirect Effects via DNA Methylation. AB - A sample of 398 African American youth, residing in rural counties with high poverty and unemployment, were followed from ages 11 to 19. Protective parenting was associated with better health, whereas elevated socioeconomic status (SES) risk was associated with poorer health at age 19. Genome-wide epigenetic variation assessed in young adulthood (age 19), was associated with both SES risk and protective parenting. Three categories of genes were identified whose methylation was associated with parenting, SES risk, and young adult health. Methylation was a significant mediator of the impact of parenting and SES risk on young adult health. Variation in mononuclear white blood cell types was also examined and controlled, showing that it did not account for observed effects of parenting and SES risk on health. PMID- 26822449 TI - Transformative Role of Epigenetics in Child Development Research: Commentary on the Special Section. AB - Lester, Conradt, and Marsit (2016) have assembled a set of articles that bring to readers of Child Development the scope and impact of the exponentially growing research on epigenetics and child development. This commentary aims to place this work in a broader context of theory and research by (a) providing a conceptual framework for developmental scientists who may be only moderately familiar with this emergent field; (b) considering these contributions in relation to the current status of work, highlighting its transformative nature; (c) suggesting cautions to keep in mind, while simultaneously clarifying that these do not undermine important new insights; and (d) identifying the prospects for future work that builds on the progress reflected in this special section. PMID- 26822450 TI - Middle Childhood Support-Seeking Behavior During Stress: Links With Self-Reported Attachment and Future Depressive Symptoms. AB - This study tested whether children's more anxious and avoidant attachment is linked to decreased support-seeking behavior toward their mother during stress in middle childhood, and whether children's decreased support-seeking behavior enhances the impact of experiencing life events on the increase of depressive symptoms 18 months later. Ninety-eight 8- to 12-year-old children filled out questionnaires assessing their level of anxious and avoidant attachment and depressive symptoms. Children's support-seeking behavior was observed through measuring the time children waited before calling for their mother's help while carrying out a stressful task. Results supported the hypothesis that more anxiously or avoidantly attached children waited longer before seeking maternal support. Moreover, waiting longer was related to increased depressive symptoms at follow-up in children who reported more experienced life events. PMID- 26822451 TI - Fullerene peapod nanoparticles as an organic semiconductor-electrode interface layer. AB - A syndiotactic poly(methyl methacrylate) bottlebrush polymer has been shown to complex with C60 fullerene and assemble into nanoparticles that can be dispersed in polar organic solvents. This composite material was used as an electrode interlayer in organic solar cell (OSC) devices leading to enhanced device performance. PMID- 26822452 TI - Quantifying soluble carbohydrates in tropical leaves using a portable mid infrared sensor: Implications for primate feeding ecology. AB - Identifying the nutritional composition of food items has significant ramifications for primate feeding ecology, which, in turn, influences investigations of primate sociality, cognition, and conservation. The aim of our study was to analyze water soluble carbohydrate (WSC) concentrations in the leaves of trees common to the Diani Forest of Kenya. Many of these leaves are consumed by black and white colobus monkeys (Colobus angolensis palliatus). We assessed whether the infrared spectral data collected using a portable spectrometer can be used to accurately predict WSC concentrations. WSC content was first quantified using the phenol-sulfuric acid method for young and mature leaves of 24 species and ranged from 1.15% to 9.16% dry weight. Spectral data were recorded with a spectrometer equipped with an attenuated total reflectance accessory (Agilent Cary 630) and analyzed using partial least squares regression. The spectral region from 1600 cm(-1) to 1000 cm(-1) gave unique polysaccharide bands associated with carboxyl, acetyl, and glycosidic linkages of sugar residues. The multivariate analysis gave excellent performance parameters with correlation coefficient (r(2) ) of 0.95 and standard error of cross-validation of 0.6% WSC. We found that IR spectroscopy provides a rapid and accurate technique for analyzing WSC concentrations and offers primatologists many advantages over wet chemistry methods for analyzing nutritional composition. Am. J. Primatol. 78:701-706, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26822448 TI - Oxytocin Receptor Genetic and Epigenetic Variations: Association With Child Abuse and Adult Psychiatric Symptoms. AB - Childhood abuse can alter biological systems and increase risk for adult psychopathology. Epigenetic mechanisms, alterations in DNA structure that regulate the gene expression, are a potential mechanism underlying this risk. While abuse associates with methylation of certain genes, particularly those in the stress response system, no study to date has evaluated abuse and methylation of the oxytocin receptor (OXTR). However, studies support a role for OXTR in the link between abuse and adverse adult outcomes, showing that abuse can confer greater risk for psychiatric symptoms in those with specific OXTR genotypes. This study therefore sought to (a) assess the role of epigenetics in the link between abuse and psychopathology and (b) begin to integrate the genetic and epigenetic literature by exploring associations between OXTR genotypes and DNA CpG methylation. Data on 18 OXTR CpG sites, 44 single nucleotide polymorphisms, childhood abuse, and adult depression and anxiety symptoms were assessed in 393 African American adults (age = 41 +/- 12.8 years). Overall, 68% of genotypes were associated with methylation of nearby CpG sites, with a subset surviving multiple test correction. Child abuse associated with higher methylation of two CpG sites yet did not survive correction or serve as a mediator of psychopathology. However, abuse interacted with CpG methylation to predict psychopathology. These findings suggest a role for OXTR in understanding the influence of early environments on adult psychiatric symptoms. PMID- 26822453 TI - Oncofertility and the Rights to Future Fertility. AB - The field of oncofertility, or fertility preservation for patients facing a cancer diagnosis, has seen significant scientific breakthroughs that allow adults and children undergoing fertility-threatening cancer treatment to preserve their fertility for a life after cancer. These breakthroughs also raise complex legal issues for patients and clinicians. While the current scholarship tangentially discusses the disposition of genetic material in regards to pediatric patients, this Special Communication examines the current legal framework as applied to disputes regarding the disposition of genetic material between the oncofertility patient and donor, and provides a potential new solution for courts to use in determining the rights of parties in disputes involving donated genetic material. PMID- 26822454 TI - A profile of volatile organic compounds in exhaled air as a potential non invasive biomarker for liver cirrhosis. AB - Early diagnosis of liver cirrhosis may prevent progression and development of complications. Liver biopsy is the current standard, but is invasive and associated with morbidity. We aimed to identify exhaled volatiles within a heterogeneous group of chronic liver disease (CLD) patients that discriminates those with compensated cirrhosis (CIR) from those without cirrhosis, and compare this with serological markers. Breath samples were collected from 87 CLD and 34 CIR patients. Volatiles in exhaled air were measured by gas chromatography mass spectrometry. Discriminant Analysis was performed to identify the optimal panel of serological markers and VOCs for classifying our patients using a random training set of 27 CIR and 27 CLD patients. Two randomly selected independent internal validation sets and permutation test were used to validate the model. 5 serological markers were found to distinguish CIR and CLD patients with a sensitivity of 0.71 and specificity of 0.84. A set of 11 volatiles discriminated CIR from CLD patients with sensitivity of 0.83 and specificity of 0.87. Combining both did not further improve accuracy. A specific exhaled volatile profile can predict the presence of compensated cirrhosis among CLD patients with a higher accuracy than serological markers and can aid in reducing liver biopsies. PMID- 26822456 TI - The pH-responsive behaviour of poly(acrylic acid) in aqueous solution is dependent on molar mass. AB - Fluorescence spectroscopy on a series of aqueous solutions of poly(acrylic acid) containing a luminescent label showed that polymers with molar mass, Mn < 16.5 kDa did not exhibit a pH responsive conformational change, which is typical of higher molar mass poly(acrylic acid). Below this molar mass, polymers remained in an extended conformation, regardless of pH. Above this molar mass, a pH-dependent conformational change was observed. Diffusion-ordered nuclear magnetic resonance spectroscopy confirmed that low molar mass polymers did not undergo a conformational transition, although large molar mass polymers did exhibit pH dependent diffusion. PMID- 26822455 TI - Translation Microscopy (TRAM) for super-resolution imaging. AB - Super-resolution microscopy is transforming our understanding of biology but accessibility is limited by its technical complexity, high costs and the requirement for bespoke sample preparation. We present a novel, simple and multi color super-resolution microscopy technique, called translation microscopy (TRAM), in which a super-resolution image is restored from multiple diffraction limited resolution observations using a conventional microscope whilst translating the sample in the image plane. TRAM can be implemented using any microscope, delivering up to 7-fold resolution improvement. We compare TRAM with other super-resolution imaging modalities, including gated stimulated emission deletion (gSTED) microscopy and atomic force microscopy (AFM). We further developed novel 'ground-truth' DNA origami nano-structures to characterize TRAM, as well as applying it to a multi-color dye-stained cellular sample to demonstrate its fidelity, ease of use and utility for cell biology. PMID- 26822457 TI - Gracilaria edulis exhibit antiproliferative activity against human lung adenocarcinoma cell line A549 without causing adverse toxic effect in vitro and in vivo. AB - In the present study, the antiproliferative potential of various solvent extracts of Gracilaria edulis (GE) was tested against various cancer cell lines. In the A549 lung cancer cell line model, GE ethyl acetate extract (GEEA) (100 MUg mL( 1)) treated group showed the maximum and significant (P < 0.05) growth inhibition at 48 h. The IC50 value was found to be 24.5 +/- 19.1 MUg mL(-1) at 48 h. Moreover, a low level of LDH release was observed at 48 h at various concentrations of (40, 60, 80 and 100 MUg mL(-1)) GEEA extract-treated group compared to a control group. Changes in the cell morphology and echinoid spikes formation were observed at 48 h. Safety evaluation of GEEA in a non-cancerous liver cell line, PBMC and in Wistar rats positively revealed that the extract did not show any adverse toxic effects. The GEEA extract was partially purified by column chromatography and the active fraction was characterized through LC-MS analysis. Furthermore, HPLC and FT-IR analysis of the active fractions confirmed the presence of phytol, a diterpene compound with potent antiproliferative activity, which positively suggests that the red alga G. edulis contains a potent anticancer active principle. PMID- 26822458 TI - Knowledge, attitude and practice of exercise for plasma blood glucose control among patients with type-2 diabetes. AB - AIMS: Exercise plays significant role in the health outcomes of patients with diabetes, however, little is known about patients' knowledge of exercise for plasma blood glucose control among patients with type-2 diabetes (T2D). This study investigated knowledge, attitude and practice (KAP) of exercise for plasma blood glucose control among patients with T2D. MATERIALS AND METHODS: This cross sectional study recruited 299 patients with T2D (male=105; female=194) from selected government hospitals in Osun State, Nigeria using purposive sampling technique. Validated questionnaires were used to assess of exercise for plasma blood glucose control and socioeconomic status (SES) of the patients. Data were analysed using descriptive and inferential statistics. Alpha level was set at <0.05. RESULTS: The mean age of respondents was 51.9+/-9.8 years. A majority, 245(81.9%) were married individuals and more than half, 195(65.3%) were in the low SES. One hundred and forty-eight (49.5%) had good knowledge of exercise whilst 269(90.0%) had negative attitude to exercise practice. Less than a third, 82(27.4%) engaged in exercise practice for plasma blood glucose control. There was significant association between knowledge and practice of exercise ((2)=12.535; p=0.002). Furthermore, significant associations were found between knowledge and gender ((2)=11.453; p=0.003), and socioeconomic status ((2)=29.127, p=0.001) but not associated with attitude towards exercise (p>0.05). CONCLUSION: Patients with demonstrated good knowledge of exercise for plasma blood glucose control but reported negative attitude and poor practice of exercise. PMID- 26822459 TI - Mediterranean diet and metabolic syndrome prevalence in type 2 diabetes patients in Ahvaz, southwest of Iran. AB - AIMS: Metabolic syndrome as a cardiovascular disease predictor, is proposed to be reduced by following a Mediterranean diet. This study was aimed to explore the relationships between metabolic syndrome and Mediterranean diet in type 2 diabetes mellitus patients. MATERIALS: A cross-sectional study was performed on 158 type 2 diabetes mellitus patients 28-75 years old (mean age: 54.3+/-9.6 yrs). Fasting glucose and lipid profile were measured. Blood pressure and anthropometric characteristics of each participant were recorded. Food frequency questionnaires were evaluated using an 11-item score to determine the adherence to Mediterranean diet. RESULTS: Totally, 55.4% of participants had a good adherence to Mediterranean diet. The risk of metabolic syndrome in women was significantly higher than in men (OR=8.65, CI 95%=2.88-25.99; p<0.001). Nuts, legumes and seeds consumption were associated with a significant lower risk of metabolic syndrome (OR=0.42, CI 95%=0.188-0.917; p<0.05). No considerable association was observed between metabolic syndrome and adherence to Mediterranean diet (p=0.167). CONCLUSIONS: Results demonstrated no association between Mediterranean diet adherence and metabolic syndrome in type 2 diabetes mellitus patients. However, nuts, legumes and seeds might have greater benefits for diabetics. PMID- 26822461 TI - Supervised group-exercise therapy versus home-based exercise therapy: Their effects on Quality of Life and cardiovascular risk factors in women with type 2 diabetes. AB - OBJECTIVES: Exercise is an integral part of diabetes care. In Iranian women with type II diabetes, we compared the effects of supervised group exercise therapy with the effects of home-based exercise therapy on health-related quality of life (HRQOL), anthropometric parameters, glycaemic control and lipid profile. MATERIALS AND METHODS: One hundred and two diabetic women were randomised to supervised and home-based groups. METHODS: Over 12 weeks, participants received supervised group-exercise therapy or a home-based exercise-therapy program. During the intervention, they were assessed three times: at baseline, and at weeks 6 and 12. Generalized Estimating Equation models were used to examine the associations between the type of exercise-therapy program and changes over time in anthropometric and biochemical outcomes, and in HRQOL scales of SF36 questionnaire. RESULTS: Relative to home-based group, supervised group improved significantly regarding role-physical, general health, mean body weight and body mass index from baseline to week 12 (p=0.01). Their reduction in mean body-fat mass from baseline to week 6 (p=0.04) was greater. Similarly, their role physical, general health and role-emotional improved significantly during the intervention (p<0.05). From baseline to the twelfth week, the HbA1c level fell significantly (p<0.05) in both groups. CONCLUSIONS: Supervised group-exercise therapy was more effective than home-based exercise therapy in improving HRQOL and body composition in diabetic women. However, home-based exercise therapy also produced significant improvements in glycaemic control, body composition and lipid profile. Whether in a supervised or home-based setting, the exercise intervention can therefore be effective in improving health outcomes in diabetic patients. PMID- 26822460 TI - Effect of obesity and glycated hemoglobin on oxygen saturation in ambulatory type 2 diabetic individuals: A pilot study. AB - AIMS: Tissue hypoxia is an important contributor to diabetic complications. Glycation of hemoglobin (Hb) and obesity are major determinant of oxygen saturation (SpO2) in blood. Hence, the present study was planned to evaluate the effect of obesity on SpO2 in a wide range of glycated hemoglobin (HbA1c) levels in ambulatory type 2 diabetic patients. MATERIAL AND METHODS: A cohort of 60 subjects irrespective of diabetic status were recruited and clustered in group I (HbA1c <6.5) and group II (HbA1c >=6.5) depending on HbA1c. Anthropometry and routine biochemical parameters were measured. HbA1c (%) were estimated by high performance liquid chromatography (HPLC) respectively. SpO2 (%) levels were measured by pulse oximetry. Pearson correlation, bivariate regression and student 't' test were used for statistical analysis. RESULTS: Blood concentration of HbA1c was <6.5 in 29 participants and >=6.5 in 31 participants. Plasma fasting and post prandial glucose, HbA1c as well as Hb levels were significantly (p<0.50) higher in diabetics as compared to non diabetics. Waist circumference (WC) (r= 400; p=0.026) and body mass index (BMI) (r=-381; p=0.034) showed a significant negative correlation with SpO2 in diabetic patients. On adjusting HbA1c in group II, SpO2 was found to independently and inversely associated with WC (p=0.042) and BMI (p=0.049). CONCLUSIONS: Obesity was found to be a strong independent contributor to reduction in oxygen carrying capacity in ambulatory type 2 diabetic subjects. However there is no effect of glycated Hb on SpO2 in the same population. PMID- 26822462 TI - Insulin glargine versus insulin degludec in patients failing on oral therapy in type 2 diabetes: A retrospective real world comparative data from India. AB - OBJECTIVE: To compare the changes in various glycemic parameters in insulin-naive type 2 diabetes mellitus (DM) patients who were initiated on insulin glargine or insulin degludec in a real world setting. METHODS: Retrospective data were analyzed in consecutive type 2 DM patients in a real world setting, who failed oral therapy (at least 2 oral anti-diabetic drugs) and were initiated with either insulin glargine or insulin degludec. The parameters assessed were the changes in HbA1c, fasting plasma glucose, body weight, dose of Insulin and the total number of patient reported hypoglycemic episodes up to 6 months after initiation. RESULT: At baseline, insulin glargine and insulin degludec groups were similar in terms of gender, age, weight, HbA1c and duration of diabetes. After 6 months follow up the change in HbA1c (-1.09 versus -1.45 P=0.124), change in FPG ( 72.81mg/dl [-4mmol/L] versus -75.88mg/dl [-4.2mmol/L] P=0.755), and the change in body weight (+1.65 versus +0.85 P=0.082) were similar in glargine and degludec groups, respectively. Patients in insulin degludec group experienced significantly lesser patient reported hypoglycemic episodes (12 versus 40) and required significantly lesser dose (25.68Units versus 18.61Units per day; P=0.002) compared to insulin glargine. 41% of the patients reached HbA1C target of <=7% with insulin glargine compared to 69% with insulin degludec within the specified time period. CONCLUSION: Results from this real world analysis suggest that among type 2 DM patients who were initiated on insulin degludec as compared to insulin glargine may be associated with significantly lesser patient reported hypoglycemic episodes and lesser dose of insulin while achieving similar glycemic control. This study is however limited by the retrospective nature of the data collection. PMID- 26822463 TI - Electroactive polyurethane/siloxane derived from castor oil as a versatile cardiac patch, part II: HL-1 cytocompatibility and electrical characterizations. AB - In first part of this experiment, biocompatibility of the newly developed electroactive polyurethane/siloxane films containing aniline tetramer moieties was demonstrated with proliferation and differentiation of C2C12 myoblasts. Here we further assessed the cytocompatibility of the prepared samples with HL1-cell line, the electrophysiological properties and the patch clamp recording of the seeded cells over the selected electroactive sample. Presence of electroactive aniline tetramer in the structure of polyurethane/siloxane led to the increased expression of cardiac-specific genes of HL-1 cells involved in muscle contraction and electrical coupling. Our results showed that expression of Cx43, TrpT-2, and SERCA genes was significantly increased in conductive sample compared to tissue culture plate and the corresponding non-conductive analogous. The prepared materials were not only biocompatible in terms of cellular toxicity, but did not alter the intrinsic electrical characteristics of HL-1 cells. Embedding the electroactive moiety into the prepared films improved the properties of these polymeric cardiac construct through the enhanced transmission of electrical signals between the cells. Based on morphological observation, calcium imaging and electrophysiological recordings, we demonstrated the potential applicability of these materials for cardiac tissue engineering. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1398-1407, 2016. PMID- 26822464 TI - Simultaneous thoraco-laparoscopic repair of giant hiatal hernias: an alternative approach. AB - Laparoscopic repair of giant hiatal hernias with intrathoracic displacement of organs is recommended to relieve troublesome symptoms in patients. During this procedure, incomplete excision of the hernia sac from the mediastinum and omission of creating a 'non-tension-free position' of the cardio-esophageal junction into the abdominal cavity are associated with hiatal hernia recurrence. Giant hiatal hernias therefore often require a thoracotomy or thoracoscopy, to free dense adhesions higher up the chest. These procedures may increase the risk of perioperative morbidity due to lengthy operating times. We developed an operation procedure for giant hiatal hernia repair containing all the benefits of minimal invasive surgery, with overview of both thoracic and abdominal herniated structures. Three patients with a giant hiatal hernia were treated by a simultaneous thoraco-laparoscopic approach, which proved to be technically feasible and safe. Simultaneous thoraco-laparoscopic hernia repair can be considered a reasonable treatment option in selected cases such as type IV hernias, hernia recurrence or traumatic diaphragmatic herniation. PMID- 26822465 TI - The influence of speech rate and accent on access and use of semantic information. AB - Circumstances in which the speech input is presented in sub-optimal conditions generally lead to processing costs affecting spoken word recognition. The current study indicates that some processing demands imposed by listening to difficult speech can be mitigated by feedback from semantic knowledge. A set of lexical decision experiments examined how foreign accented speech and word duration impact access to semantic knowledge in spoken word recognition. Results indicate that when listeners process accented speech, the reliance on semantic information increases. Speech rate was not observed to influence semantic access, except in the setting in which unusually slow accented speech was presented. These findings support interactive activation models of spoken word recognition in which attention is modulated based on speech demands. PMID- 26822466 TI - Ultra-fast stem cell labelling using cationised magnetoferritin. AB - Magnetic cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) facilitates many important biotechnological applications, such as cell imaging and remote manipulation. However, to achieve adequate cellular loading of SPIONs, long incubation times (24 hours and more) or laborious surface functionalisation are often employed, which can adversely affect cell function. Here, we demonstrate that chemical cationisation of magnetoferritin produces a highly membrane-active nanoparticle that can magnetise human mesenchymal stem cells (hMSCs) using incubation times as short as one minute. Magnetisation persisted for several weeks in culture and provided significant T2* contrast enhancement during magnetic resonance imaging. Exposure to cationised magnetoferritin did not adversely affect the membrane integrity, proliferation and multi-lineage differentiation capacity of hMSCs, which provides the first detailed evidence for the biocompatibility of magnetoferritin. The combination of synthetic ease and flexibility, the rapidity of labelling and absence of cytotoxicity make this novel nanoparticle system an easily accessible and versatile platform for a range of cell-based therapies in regenerative medicine. PMID- 26822467 TI - The role of PET/CT as a prognosticator and outcome predictor in lung cancer. AB - Positron emission tomography/computed tomography (PET/CT) is an important imaging tool for management of lung cancer and can be utilized in diagnosis, staging, restaging, treatment planning and evaluating treatment response. In the past decade PET/CT has proven to be beneficial for the prediction of prognosis and outcome. PET findings before and after treatment, the quantitative PET parameters such as standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) as well as delayed PET/CT imaging can be used to determine patient prognosis and outcome. Other tracers such as hypoxia and proliferation marker tracers may be used for prognostication. The prognostic factors derived from PET/CT imaging help early development of risk-adapted treatment strategies, which provides cost-effective treatment and leads to improved patient management. Here, we discuss findings of studies related to application of PET/CT in lung cancer as well as some technical updates on quantitative PET/CT in lung cancer. PMID- 26822468 TI - Melanoma and non-melanoma skin cancer in psoriatic patients treated with high dose phototherapy. AB - OBJECTIVES: The carcinogenic effect of plus ultraviolet A (PUVA)-therapy in psoriatic patients has been widely demonstrated, while data on the safety of narrow band (311 nm) ultraviolet B (nb-UVB) are scarce. We investigated the occurrence of melanoma and non-melanoma skin cancer (NMSC) in psoriatic patients treated with nb-UVB or PUVA-therapy. METHODS: This retrospective study included patients affected by psoriasis, who had been treated with nb-UVB or PUVA-therapy. Clinical data and phenotypic risk factors were collected and a total body examination was performed at a routine appointment during the study period. RESULTS: We examined 92 patients (60 males and 32 females; mean age: 53.5 years, range: 20-83 years) treated with PUVA-therapy (42/92, 45%) or with nb-UVB (50/92, 55%) for 1-28 years (mean: 7.1 years). Among patients treated with PUVA, nine skin tumors (one melanoma, seven basal cell carcinoma (BCCs) and one squamous cell carcinoma (SCC)) were detected in 2/42 (4.7%) patients, while in the nb-UVB group, 14 skin tumors including two melanomas, four BCCs, and eight SCCs were diagnosed in 6/50 (12%) patients. CONCLUSIONS: A noteworthy number of NMSC were diagnosed in this Mediterranean population of patients exposed to high-dose UV treatment. A thorough risk-benefit evaluation should always be done before UV treatment and patients should be carefully monitored for skin cancer during and after treatment discontinuation. PMID- 26822469 TI - Serotype and genetic diversity of human rhinovirus strains that circulated in Kenya in 2008. AB - BACKGROUND: Human rhinoviruses (HRVs) are a well-established cause of the common cold and recent studies indicated that they may be associated with severe acute respiratory illnesses (SARIs) like pneumonia, asthma, and bronchiolitis. Despite global studies on the genetic diversity of the virus, the serotype diversity of these viruses across diverse geographic regions in Kenya has not been characterized. OBJECTIVES: This study sought to characterize the serotype diversity of HRV strains that circulated in Kenya in 2008. METHODS: A total of 517 archived nasopharyngeal samples collected in a previous respiratory virus surveillance program across Kenya in 2008 were selected. Participants enrolled were outpatients who presented with influenza-like (ILI) symptoms. Real-time RT PCR was employed for preliminary HRV detection. HRV-positive samples were amplified using RT-PCR and thereafter the nucleotide sequences of the amplicons were determined followed by phylogenetic analysis. RESULTS: Twenty-five percent of the samples tested positive for HRV. Phylogenetic analysis revealed that the Kenyan HRVs clustered into three main species comprising HRV-A (54%), HRV-B (12%), and HRV-C (35%). Overall, 20 different serotypes were identified. Intrastrain sequence homology among the Kenyan strains ranged from 58% to 100% at the nucleotide level and 55% to 100% at the amino acid level. CONCLUSION: These results show that a wide range of HRV serotypes with different levels of nucleotide variation were present in Kenya. Furthermore, our data show that HRVs contributed substantially to influenza-like illness in Kenya in 2008. PMID- 26822471 TI - Evaluation of fire recurrence effect on genetic diversity in maritime pine (Pinus pinaster Ait.) stands using Inter-Simple Sequence Repeat profiles. AB - The management of maritime pine in fire-prone habitats is a challenging task and fine-scale population genetic analyses are necessary to check if different fire recurrences affect genetic variability. The objective of this study was to assess the effect of fire recurrence on maritime pine genetic diversity using inter simple sequence repeat markers (ISSR). Three maritime pine (Pinus pinaster Ait.) populations from Northern Portugal were chosen to characterize the genetic variability among populations. In relation to fire recurrence, Seiros population was affected by fire both in 1990 and 2005 whereas Vila Seca-2 population was affected by fire just in 2005. The Vila Seca-1 population has been never affected by fire. Our results showed the highest Nei's genetic diversity (He=0.320), Shannon information index (I=0.474) and polymorphic loci (PPL=87.79%) among samples from twice burned populations (Seiros site). Thus, fire regime plays an important role affecting genetic diversity in the short-term, although not generating maritime pine genetic erosion. PMID- 26822470 TI - Comparison of potential preventive effects of pomegranate flower, peel and seed oil on insulin resistance and inflammation in high-fat and high-sucrose diet induced obesity mice model. AB - OBJECTIVE: The potentially beneficial effects of pomegranate peel (PPE), flower (PFE) and seed oil (PSO) extracts, in comparison with rosiglitazone, on adiposity, lipid profile, glucose homoeostasis, as well as on the underlying inflammatory mechanisms, were examined in high-fat and high-sucrose (HF/HS) diet induced obese (DIO) mice. MEASUREMENTS: Body weight, body fat, energy expenditure, food and liquid intake, blood glucose, and plasma levels of insulin, lipids and cytokines were measured. RESULTS: After two weeks, PSO (2 ml/kg/day) and rosiglitazone (3 mg/kg/day) had not improved glucose intolerance. After 4 weeks, both treatments significantly reduced fasting blood glucose and an insulin tolerance test showed that they also improved insulin sensitivity. Treatment with PPE, PFE and PSO, reduced the plasma levels of the pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), and PFE increased the level of the anti-inflammatory cytokine interleukin-10 (IL-10). CONCLUSION: PPE, PFE and PSO have anti-inflammatory properties. PSO also improved insulin sensitivity. PMID- 26822472 TI - Fugitive emissions of methane from abandoned, decommissioned oil and gas wells. AB - This study considered the fugitive emissions of methane (CH4) from former oil and gas exploration and production wells drilled to exploit conventional hydrocarbon reservoirs onshore in the UK. This study selected from the 66% of all onshore wells in the UK which appeared to be properly decommissioned (abandoned) that came from 4 different basins and were between 8 and 79 years old. The soil gas above each well was analysed and assessed relative to a nearby control site of similar land use and soil type. The results showed that of the 102 wells considered 30% had soil gas CH4 at the soil surface that was significantly greater than their respective control. Conversely, 39% of well sites had significant lower surface soil gas CH4 concentrations than their respective control. We interpret elevated soil gas CH4 concentrations to be the result of well integrity failure, but do not know the source of the gas nor the route to the surface. Where elevated CH4 was detected it appears to have occurred within a decade of it being drilled. The flux of CH4 from wells was 364 +/- 677 kg CO2eq/well/year with a 27% chance that the well would have a negative flux to the atmosphere independent of well age. This flux is low relative to the activity commonly used on decommissioned well sites (e.g. sheep grazing), however, fluxes from wells that have not been appropriately decommissioned would be expected to be higher. PMID- 26822473 TI - Septic systems as sources of organic wastewater compounds in domestic drinking water wells in a shallow sand and gravel aquifer. AB - Domestic drinking water wells serve 44 million people in the US and are common globally. They are often located in areas served by onsite wastewater treatment systems, including septic systems, which can be sources of biological and chemical pollutants to groundwater. In this study we tested 20 domestic drinking water wells in a sand and gravel aquifer on Cape Cod, Massachusetts, USA, for 117 organic wastewater compounds (OWCs) and for inorganic markers of septic system impact. We detected 27 OWCs, including 12 pharmaceuticals, five per- and polyfluoroalkyl substances (PFASs), four organophosphate flame retardants, and an artificial sweetener (acesulfame). Maximum concentrations of several PFASs and pharmaceuticals were relatively high compared to public drinking water supplies in the US. The number of detected OWCs and total concentrations of pharmaceuticals and of PFASs were positively correlated with nitrate, boron, and acesulfame and negatively correlated with well depth. These wells were all located in areas served exclusively by onsite wastewater treatment systems, which are likely the main source of the OWCs in these wells, although landfill leachate may also be a source. Our results suggest that current regulations to protect domestic wells from pathogens in septic system discharges do not prevent OWCs from reaching domestic wells, and that nitrate, a commonly measured drinking water contaminant, is a useful screening tool for OWCs in domestic wells. Nitrate concentrations of 1mg/L NO3-N, which are tenfold higher than local background and tenfold lower than the US federal drinking water standard, were associated with wastewater impacts from OWCs in this study. PMID- 26822474 TI - A brief report on Hispanic youth marijuana use: Trends in substance abuse treatment admissions in the United States. AB - Increases in Hispanic youth admissions to substance abuse treatment programs for marijuana use are a growing public health concern. In this study, we investigated trends in Hispanic youth from 1995 to 2012 utilizing the Treatment Episode Data Set-Admissions of the Substance Abuse Mental Health Services Administration. Hispanic youth marijuana admissions are associated with youth 15-17 years old, in high school, and living in a dependent situation. Notably, female admissions increased at greater rates than males. Results also point to decreasing tolerance of minor marijuana use by schools and community agencies. Findings highlight the need for targeted, culturally specific, and cost-effective treatment and prevention efforts. PMID- 26822475 TI - ISMRM Raw data format: A proposed standard for MRI raw datasets. AB - PURPOSE: This work proposes the ISMRM Raw Data format as a common MR raw data format, which promotes algorithm and data sharing. METHODS: A file format consisting of a flexible header and tagged frames of k-space data was designed. Application Programming Interfaces were implemented in C/C++, MATLAB, and Python. Converters for Bruker, General Electric, Philips, and Siemens proprietary file formats were implemented in C++. Raw data were collected using magnetic resonance imaging scanners from four vendors, converted to ISMRM Raw Data format, and reconstructed using software implemented in three programming languages (C++, MATLAB, Python). RESULTS: Images were obtained by reconstructing the raw data from all vendors. The source code, raw data, and images comprising this work are shared online, serving as an example of an image reconstruction project following a paradigm of reproducible research. CONCLUSION: The proposed raw data format solves a practical problem for the magnetic resonance imaging community. It may serve as a foundation for reproducible research and collaborations. The ISMRM Raw Data format is a completely open and community-driven format, and the scientific community is invited (including commercial vendors) to participate either as users or developers. Magn Reson Med 77:411-421, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26822476 TI - Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development. AB - Lipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts ofLrp2knockout (KO) mice have not yet been investigated. We studied the cardiovascular development ofLrp2KO mice between embryonic day 10.5 (E10.5) and E15.5, applying morphometry and immunohistochemistry, using antibodies against Tfap2alpha (neural crest cells), Nkx2.5 (second heart field), WT1 (epicardium derived cells), tropomyosin (myocardium) and LRP2. TheLrp2KO mice display a range of severe cardiovascular abnormalities, including aortic arch anomalies, common arterial trunk (persistent truncus arteriosus) with coronary artery anomalies, ventricular septal defects, overriding of the tricuspid valve and marked thinning of the ventricular myocardium. Both the neural crest cells and second heart field, which are essential for the lengthening and growth of the right ventricular outflow tract, are abnormally positioned in theLrp2KO. This explains the absence of the aorto pulmonary septum, which leads to common arterial trunk and ventricular septal defects. Severe blebbing of the epicardial cells covering the ventricles is seen. Epithelial-mesenchymal transition does occur; however, there are fewer WT1 positive epicardium-derived cells in the ventricular wall as compared to normal, coinciding with the myocardial thinning and deep intertrabecular spaces. LRP2 plays a crucial role in cardiovascular development in mice. This corroborates findings of cardiac anomalies in humans withLRP2mutations. Future studies should reveal the underlying signaling mechanisms in which LRP2 is involved during cardiogenesis. PMID- 26822477 TI - Depletion of regulatory T cells leads to an exacerbation of delayed-type hypersensitivity arthritis in C57BL/6 mice that can be counteracted by IL-17 blockade. AB - Rodent models of arthritis have been extensively used in the elucidation of rheumatoid arthritis (RA) pathogenesis and are instrumental in the development of therapeutic strategies. Here we utilise delayed-type hypersensitivity arthritis (DTHA), a model in C57BL/6 mice affecting one paw with synchronised onset, 100% penetrance and low variation. We investigate the role of regulatory T cells (Tregs) in DTHA through selective depletion of Tregsand the role of IL-17 in connection with Tregdepletion. Given the relevance of Tregsin RA, and the possibility of developing Treg-directed therapies, this approach could be relevant for advancing the understanding of Tregsin inflammatory arthritis. Selective depletion of Tregswas achieved using aFoxp3-DTR-eGFPmouse, which expresses the diphtheria toxin receptor (DTR) and enhanced green fluorescent protein (eGFP) under control of theFoxp3gene. Anti-IL-17 monoclonal antibody (mAb) was used for IL-17 blockade. Numbers and activation of Tregsincreased in the paw and its draining lymph node in DTHA, and depletion of Tregsresulted in exacerbation of disease as shown by increased paw swelling, increased infiltration of inflammatory cells, increased bone remodelling and increased production of inflammatory mediators, as well as increased production of anti citrullinated protein antibodies. Anti-IL-17 mAb treatment demonstrated that IL 17 is important for disease severity in both the presence and absence of Tregs, and that IL-17 blockade is able to rescue mice from the exacerbated disease caused by Tregdepletion and caused a reduction in RANKL, IL-6 and the number of neutrophils. We show that Tregsare important for the containment of inflammation and bone remodelling in DTHA. To our knowledge, this is the first study using theFoxp3-DTR-eGFPmouse on a C57BL/6 background for Tregdepletion in an arthritis model, and we here demonstrate the usefulness of the approach to study the role of Tregsand IL-17 in arthritis. PMID- 26822479 TI - Erratum to: Homicide in Chile: Trends 2000 - 2012. PMID- 26822478 TI - Tau excess impairs mitosis and kinesin-5 function, leading to aneuploidy and cell death. AB - In neurodegenerative diseases such as Alzheimer's disease (AD), cell cycle defects and associated aneuploidy have been described. However, the importance of these defects in the physiopathology of AD and the underlying mechanistic processes are largely unknown, in particular with respect to the microtubule (MT) binding protein Tau, which is found in excess in the brain and cerebrospinal fluid of affected individuals. Although it has long been known that Tau is phosphorylated during mitosis to generate a lower affinity for MTs, there is, to our knowledge, no indication that an excess of this protein could affect mitosis. Here, we studied the effect of an excess of human Tau (hTau) protein on cell mitosis in vivo. Using the Drosophila developing wing disc epithelium as a model, we show that an excess of hTau induces a mitotic arrest, with the presence of monopolar spindles. This mitotic defect leads to aneuploidy and apoptotic cell death. We studied the mechanism of action of hTau and found that the MT-binding domain of hTau is responsible for these defects. We also demonstrate that the effects of hTau occur via the inhibition of the function of the kinesin Klp61F, the Drosophila homologue of kinesin-5 (also called Eg5 or KIF11). We finally show that this deleterious effect of hTau is also found in other Drosophila cell types (neuroblasts) and tissues (the developing eye disc), as well as in human HeLa cells. By demonstrating that MT-bound Tau inhibits the Eg5 kinesin and cell mitosis, our work provides a new framework to consider the role of Tau in neurodegenerative diseases. PMID- 26822481 TI - Implementing PRISMA-P: recommendations for prospective authors. PMID- 26822480 TI - Remifentanil in electroconvulsive therapy: a systematic review and meta-analysis of randomized controlled trials. AB - In electroconvulsive therapy (ECT), remifentanil is often used concurrently with anesthetics. The objective of this study was to provide an up-to-date and comprehensive review on how the addition of remifentanil to anesthetics affects seizure duration and circulatory dynamics in mECT. We performed a meta-analysis of RCTs that investigated seizure duration and circulatory dynamics in patients treated with ECT using anesthetics alone (non-remifentanil group) and with anesthetics plus remifentanil (remifentanil group). A total of 13 RCTs (380 patients and 1024 ECT sessions) were included. The remifentanil group showed a significantly prolonged seizure duration during ECT compared to the non remifentanil group [motor: 9 studies, SMD = 1.25, 95 % CI (0.21, 2.29), p = 0.02; electroencephalogram: 8 studies, SMD = 0.98, 95 % CI (0.14, 1.82), p = 0.02]. The maximum systolic blood pressure (SBP) was significantly reduced in the remifentanil group compared to the non-remifentanil group [7 studies, SMD = 0.36, 95 % CI (-0.65, 0.07), p = 0.02]. Substantial heterogeneity was observed for meta-analyses for seizure durations, but a pre-planned subgroup analysis revealed that seizure duration was prolonged only when the use of the anesthetic dose was reduced in the remifentanil group. The results of our study suggest that addition of remifentanil to anesthesia in ECT may lead to prolonged seizure duration when it allows the use of reduced anesthetic doses. Further, the addition of remifentanil was associated with reduced maximum SBP. PMID- 26822482 TI - Quantitative modeling and analytic assessment of the transcription dynamics of the XlnR regulon in Aspergillus niger. AB - BACKGROUND: Transcription of genes coding for xylanolytic and cellulolytic enzymes in Aspergillus niger is controlled by the transactivator XlnR. In this work we analyse and model the transcription dynamics in the XlnR regulon from time-course data of the messenger RNA levels for some XlnR target genes, obtained by reverse transcription quantitative PCR (RT-qPCR). Induction of transcription was achieved using low (1 mM) and high (50 mM) concentrations of D-xylose (Xyl). We investigated the wild type strain (Wt) and a mutant strain with partial loss of-function of the carbon catabolite repressor CreA (Mt). RESULTS: An improved kinetic differential equation model based on two antagonistic Hill functions was proposed, and fitted to the time-course RT-qPCR data from the Wt and the Mt by numerical optimization of the parameters. We show that perturbing the XlnR regulon with Xyl in low and high concentrations results in different expression levels and transcription dynamics of the target genes. At least four distinct transcription profiles were observed, particularly for the usage of 50 mM Xyl. Higher transcript levels were observed for some genes after induction with 1 mM rather than 50 mM Xyl, especially in the Mt. Grouping the expression profiles of the investigated genes has improved our understanding of induction by Xyl and the according regulatory role of CreA. CONCLUSIONS: The model explains for the higher expression levels at 1 mM versus 50 mM in both Wt and Mt. It does not yet fully encapsulate the effect of partial loss-of-function of CreA in the Mt. The model describes the dynamics in most of the data and elucidates the time-dynamics of the two major regulatory mechanisms: i) the activation by XlnR, and ii) the carbon catabolite repression by CreA. PMID- 26822483 TI - Lasing in Bose-Fermi mixtures. AB - Light amplification by stimulated emission of radiation, well-known for revolutionising photonic science, has been realised primarily in fermionic systems including widely applied diode lasers. The prerequisite for fermionic lasing is the inversion of electronic population, which governs the lasing threshold. More recently, bosonic lasers have also been developed based on Bose Einstein condensates of exciton-polaritons in semiconductor microcavities. These electrically neutral bosons coexist with charged electrons and holes. In the presence of magnetic fields, the charged particles are bound to their cyclotron orbits, while the neutral exciton-polaritons move freely. We demonstrate how magnetic fields affect dramatically the phase diagram of mixed Bose-Fermi systems, switching between fermionic lasing, incoherent emission and bosonic lasing regimes in planar and pillar microcavities with optical and electrical pumping. We collected and analyzed the data taken on pillar and planar microcavity structures at continuous wave and pulsed optical excitation as well as injecting electrons and holes electronically. Our results evidence the transition from a Bose gas to a Fermi liquid mediated by magnetic fields and light-matter coupling. PMID- 26822484 TI - Dendrite-Free Nanocrystalline Zinc Electrodeposition from an Ionic Liquid Containing Nickel Triflate for Rechargeable Zn-Based Batteries. AB - Metallic zinc is a promising anode material for rechargeable Zn-based batteries. However, the dendritic growth of zinc has prevented practical applications. Herein it is demonstrated that dendrite-free zinc deposits with a nanocrystalline structure can be obtained by using nickel triflate as an additive in a zinc triflate containing ionic liquid. The formation of a thin layer of Zn-Ni alloy (eta- and gamma-phases) on the surface and in the initial stages of deposition along with the formation of an interfacial layer on the electrode strongly affect the nucleation and growth of zinc. A well-defined and uniform nanocrystalline zinc deposit with particle sizes of about 25 nm was obtained in the presence of Ni(II) . Further, it is shown that the nanocrystalline Zn exhibits a high cycling stability even after 50 deposition/stripping cycles. This strategy of introducing an inorganic metal salt in ionic liquid electrolytes can be considered as an efficient way to obtain dendrite-free zinc. PMID- 26822485 TI - Is It Possible to Increase the Clinical Effectiveness of the Fracture Risk Assessment Tool in Osteopenia Patients by Taking Into Account Bone Mineral Density Values? AB - The study aimed to investigate the effectiveness of the clinical use of the Fracture Risk Assessment Tool (FRAX((r))) developed by the World Health Organization identifying patients at risk of osteoporotic fracture and to evaluate changes in osteoporotic fracture risk prediction according to bone mineral density (BMD) values. We identified the occurrence of osteoporotic fracture among patients whose BMD was measured in our hospital between April 2003 and March 2013. We then analyzed FRAX((r)) scores obtained with or without BMD on the day before the occurrence of an osteoporotic fracture in actual osteoporotic fracture patients. According to the National Osteoporosis Foundation high-risk criteria, we identified the percentage of high-risk patients before the actual fracture. Among 445 osteoporotic fracture patients, when FRAX((r))-BMD was used, 281 patients (63%) were identified as high-risk before an actual osteoporotic fracture, and when FRAX((r)) without BMD was used, 258 patients (58%) were identified (p = 0.115). In the 84 osteopenia patients, 39 patients (46.4%) were identified as high-risk when FRAX((r)) without BMD was used, and 19 patients (22.6%) were identified when FRAX((r))-BMD was used (p = 0.001). The use of BMD in FRAX((r)) does not seem to increase the clinical effectiveness of predicting osteoporotic fracture in osteopenia patients. PMID- 26822486 TI - Children Whose Fathers Seek Help for Partner Violence Victimization: Descriptive Characteristics and Their Behavioral Health as Compared to a Population-Based Sample. AB - Children whose parents seek help for partner violence (PV) victimization are at an increased risk for internalizing and externalizing behavioral health problems. The literature has examined this phenomenon primarily among children of battered women. This study examines the sociodemographic characteristics and behavioral health of children whose fathers have sought help for PV victimization and compares them to children of men from the general population. Children whose fathers sought help for PV victimization were less likely to live with their fathers. Bivariate analyses showed that children of male victims had elevated scores in Diagnostic and Statistical Manual of Mental Disorders (DSM)-related areas of behavioral health; many of these findings remain in multivariate analyses, especially among older children. The implications of the results are discussed for researchers and social service practitioners. PMID- 26822490 TI - The Convenient Synthesis of Unsaturated Nucleoside Analogues in Water under Microwave Irradiation. AB - A convenient method for the regioselective synthesis of unsaturated nucleoside analogs in water under microwave irradiation was developed. All pyrimidine and purine nucleoside derivatives were exclusively alkylated at N1 and N9 respectively in good to excellent yields. In addition, this system could tolerate a broad range of functional groups, such as chloro, bromo, iodo, alkyl, amino, and hydroxyl groups. More importantly, the reaction scale could be enlarged to 50 mmol which made this route attractive for industrial application. PMID- 26822487 TI - A Two-Way Street: Regulatory Interplay between RNA Polymerase and Nascent RNA Structure. AB - The vectorial (5'-to-3' at varying velocity) synthesis of RNA by cellular RNA polymerases (RNAPs) creates a rugged kinetic landscape, demarcated by frequent, sometimes long-lived, pauses. In addition to myriad gene-regulatory roles, these pauses temporally and spatially program the co-transcriptional, hierarchical folding of biologically active RNAs. Conversely, these RNA structures, which form inside or near the RNA exit channel, interact with the polymerase and adjacent protein factors to influence RNA synthesis by modulating pausing, termination, antitermination, and slippage. Here, we review the evolutionary origin, mechanistic underpinnings, and regulatory consequences of this interplay between RNAP and nascent RNA structure. We categorize and rationalize the extensive linkage between the transcriptional machinery and its product, and provide a framework for future studies. PMID- 26822488 TI - Mechanisms and Dynamics of Protein Acetylation in Mitochondria. AB - Reversible protein acetylation is a major regulatory mechanism for controlling protein function. Through genetic manipulations, dietary perturbations, and new proteomic technologies, the diverse functions of protein acetylation are coming into focus. Protein acetylation in mitochondria has taken center stage, revealing that 63% of mitochondrially localized proteins contain lysine acetylation sites. We summarize the field and discuss salient topics that cover spurious versus targeted acetylation, the role of SIRT3 deacetylation, nonenzymatic acetylation, and molecular models for regulatory acetylations that display high and low stoichiometry. PMID- 26822489 TI - Prefrontal White Matter Structure Mediates the Influence of GAD1 on Working Memory. AB - The glutamic acid decarboxylase 1 (GAD1) gene is a major determinant of gamma aminobutyric acid (GABA), the most abundant inhibitory neurotransmitter modulating local neuronal circuitry. GABAergic dysfunction and expression of GAD1 have been implicated in the pathophysiology of schizophrenia, and in working memory impairment. We examined the influence of the functional GAD1 rs3749034 variant on white matter fractional anisotropy (FA), cortical thickness, and working memory performance in schizophrenia patients and healthy controls (N=197). Using transcranial magnetic stimulation with electroencephalography (TMS EEG), we subsequently examined the effect of rs3749034 on long-interval cortical inhibition (LICI) in the dorsolateral prefrontal cortex (DLPFC) in schizophrenia patients and healthy controls (N=66). We found that the rs3749034 T-allele carrier risk group had lower voxel-wise FA in the prefrontal cortex region (PFWE corrected<0.05) but not cortical thickness. Mixed-model regression revealed a significant effect on attentional processing and working memory across four performance measures (F1,182=11.5, P=8 * 10(-4)). FA in the prefrontal cortex was associated with digit-span performance. Voxel-wise mediation analysis revealed that the effect GAD1 on poorer digit-span performance statistically predicted the lower white matter FA (PFWE-corrected<0.05). In exploratory analysis, we found a prominent GAD1 genotype-by-diagnosis interaction on DLPFC LICI (F1,56=14.3, P=4.1 * 10(-4)). Our findings converge on variation in GAD1 gene predicting a susceptibility mechanism that affects white matter FA, GABAergic inhibitory neurotransmission in the DLPFC, and working memory performance. Furthermore, via voxel mediation of FA and TMS-EEG intervention, we provide evidence for a potentially causal mechanism through which aberrant DLPFC GABA signaling may contribute to working memory dysfunction. PMID- 26822491 TI - Roles of CYP2C19 Gene Polymorphisms in Susceptibility to POAG and Individual Differences in Drug Treatment Response. AB - BACKGROUND: The aim of this study was to investigate the roles of cytochrome P450 2C19 (CYP2C19) polymorphisms in primary open-angle glaucoma (POAG) susceptibility and individual responses to drug treatment. MATERIAL/METHODS: This case-control study consisted of 93 cases with POAG and 125 controls. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used to analyze CYP2C19 single-nucleotide polymorphisms (SNPs). After timolol treatment, patients were classified into side effect (SE) group and non-side effect (NSE) group. According to drug treatment responses, patients were divided into 3 groups: excellent group (Ex) (IOP >=8 mm Hg); utility group (Ut) (5 0.05). Frequencies of extensive metabolizer phenotype and poor metabolizer phenotype or poor metabolizer phenotype and intermediate metabolizer phenotype were significantly different between the SE group and NSE group (both P<0.05). The distribution of intermediate metabolizer phenotype and extensive metabolizer phenotype were significantly different among Ex group, Ut group, and In group (all P<0.05). CONCLUSIONS: We found no evidence that CYP2C19 polymorphisms are associated with susceptibility to POAG. However, different CYP2C19 metabolizer phenotypes were identified and observed to have important effects on the individual differences in drug treatment response. PMID- 26822492 TI - The signal peptide peptidase SppA is involved in sterol regulatory element binding protein cleavage and hypoxia adaptation in Aspergillus nidulans. AB - Using forward genetics, we revealed that the signal peptide peptidase (SPP) SppA, an aspartyl protease involved in regulated intramembrane proteolysis (RIP), is essential for hypoxia adaptation in Aspergillus nidulans, as well as hypoxia sensitive mutant alleles of a sterol regulatory element-binding protein (SREBP) srbA and the Dsc ubiquitin E3 ligase complex dscA-E. Both null and dead activity [D337A] mutants of sppA failed to grow in hypoxia, and the growth defect of DeltasppA was complemented by nuclear SrbA-N381 expression. Additionally, SppA interacted with SrbA in the endoplasmic reticulum, where SppA localized in normoxia and hypoxia. Expression of the truncated SrbA-N414 covering the SrbA sequence prior to the second transmembrane region rescued the growth of DeltadscA but not of DeltasppA in hypoxia. Unlike DeltadscA and DeltadscA;DeltasppA double mutants, in which SrbA cleavage was blocked, the molecular weight of cleaved SrbA increased in DeltasppA compared to the control strain in immunoblot analyses. Overall, our data demonstrate the sequential cleavage of SrbA by Dsc-linked proteolysis followed by SppA, proposing a new model of RIP for SREBP cleavage in fungal hypoxia adaptation. Furthermore, the function of SppA in hypoxia adaptation was consistent in Aspergillus fumigatus, suggesting the potential roles of SppA in fungal pathogenesis. PMID- 26822493 TI - Thrombin-Induced Platelet-Fibrin Clot Strength Identified by Thrombelastography: A Novel Prothrombotic Marker of Coronary Artery Stent Restenosis. AB - BACKGROUND AND OBJECTIVE: In-stent restenosis (ISR) is a limitation of percutaneous coronary intervention and has been linked to specific clinical and angiographic variables. We aimed to simultaneously assess thrombosis biomarkers and lipid levels in patients with and without ISR. METHODS: Consecutive patients (n = 170) with a history of coronary stenting undergoing elective angiography were studied. Blood samples for thrombelastography, light transmittance aggregometry, and lipid levels were obtained prior to cardiac catheterization. RESULTS: Sixty-nine patients (41%) had ISR (>50% luminal diameter stenosis). Among patients with ISR, 40 (58%) had ISR in more than one stent bed. Patients with ISR were more often female (37.7% vs. 21.8%, P = 0.04), had higher thrombin induced platelet-fibrin clot strength (TIP-FCS) (69.9 mm vs. 65.6 mm, P < 0.001), and a higher ApoB/A1 ratio (0.65 vs. 0.59, P = 0.03). In patients on dual antiplatelet therapy (n = 86), there were no differences in ADP-, arachidonic acid-, and collagen-induced platelet aggregation between groups. The frequency of patients with ISR increased with TIP-FCS quartiles and by ROC analysis, TIP-FCS = 67.0 mm was the cutpoint for identification of ISR (AUC = 0.80 (95%CI 0.73-0.87, P < 0.0001). By multivariate analysis, TIP-FCS >=67.0 mm strongly associated with ISR (OR = 7.3, P = 0.004). CONCLUSION: Patients with ISR identified at the time of cardiac catheterization have a prothrombotic phenotype indicated by high TIP FCS, a novel marker. Studies to confirm the prognostic utility of high TIP-FCS for the development of ISR are ongoing. PMID- 26822494 TI - Compositional and Interfacial Modification of Cu2 ZnSn(S,Se)4 Thin-Film Solar Cells Prepared by Electrochemical Deposition. AB - A highly efficient Cu2 ZnSn(S,Se)4 (CZTSSe)-based thin-film solar cell (9.9%) was prepared using an electrochemical deposition method followed by thermal annealing. The Cu-Zn-Sn alloy films was grown on a Mo-coated glass substrate using a one-pot electrochemical deposition process, and the metallic precursor films was annealed under a mixed atmosphere of S and Se to form CZTSSe thin films with bandgap energies ranging from 1.0 to 1.2 eV. The compositional modification of the S/(S+Se) ratio shows a trade-off effect between the photocurrent and photovoltage, resulting in an optimum bandgap of roughly 1.14 eV. In addition, the increased S content near the p-n junction reduces the dark current and interface recombination, resulting in a further enhancement of the open-circuit voltage. As a result of the compositional and interfacial modification, the best CZTSSe-based thin-film solar cell exhibits a conversion efficiency of 9.9%, which is among the highest efficiencies reported so far for electrochemically deposited CZTSSe-based thin-film solar cells. PMID- 26822495 TI - Single-Atom Pt as Co-Catalyst for Enhanced Photocatalytic H2 Evolution. AB - Isolated single-atom platinum (Pt) embedded in the sub-nanoporosity of 2D g-C3 N4 as a new form of co-catalyst is reported. The highly stable single-atom co catalyst maximizes the atom efficiency and alters the surface trap states of g-C3 N4 , leading to significantly enhanced photocatalytic H2 evolution activity, 8.6 times higher than that of Pt nanoparticles and up to 50 times that for bare g-C3 N4 . PMID- 26822496 TI - Conservation of Hox gene clusters in the self-fertilizing fish Kryptolebias marmoratus (Cyprinodontiformes; Rivulidae). AB - In this study, whole Hox gene clusters in the self-fertilizing mangrove killifish Kryptolebias marmoratus (Cyprinodontiformes; Rivulidae), a unique hermaphroditic vertebrate in which both sex organs are functional at the same time, were identified from whole genome and transcriptome sequences. The aim was to increase the understanding of the evolutionary status of conservation of this Hox gene cluster across fish species. PMID- 26822497 TI - Comparative efficacy of vitamin D status in reducing the risk of bladder cancer: A systematic review and network meta-analysis. AB - OBJECTIVES: The optimal concentration of individual vitamin D intake for preventing bladder cancer has not, to our knowledge, been defined. To evaluate the comparative efficacy of different serum 25-hydroxyvitamin D concentrations in preventing bladder cancer, we conducted a systematic search of the literature published up to April 2015. METHODS: We applied a pairwise meta-analysis to estimate direct evidence from intervention-control studies and a network meta analysis within a Bayesian framework to combine direct and indirect evidence. Moreover, a dose-response curve was utilized to predict the optimal median serum 25-hydroxyvitamin D concentration based on the odds ratio (OR) for each quintile concentration. METHODS: Seven studies of a total of 90757 participants, including 2509 bladder cancer patients, were included. Two prospective cohort studies with 57 591 participants and 494 bladder cancer patients, and five case-control studies with 33 166 participants and 2264 bladder cancer patients. From the network meta-analysis, we observed that sufficient serum 25-hydroxyvitamin D concentrations (>75 nmol/L) were superior to all other 25-hydroxyvitamin D concentrations in decreasing the risk of bladder cancer: OR = 0.68 and 95% credible interval (CrI) 0.52 to 0.87 compared with severely deficient concentrations (<25 nmol/L); OR = 0.65 and 95% CrI 0.49 to 0.86 compared with moderately deficient concentrations (25-37.5 nmol/L); OR = 0.61 and 95% CrI 0.47 to 0.80 compared with slightly deficient concentrations (37.5-50 nmol/L); and OR = 0.65 and 95% CrI 0.48 to 0.85 compared with insufficient concentrations (50-75 nmol/L). In addition, we noted a roughly inverse correlation between bladder cancer risk and 25-hydroxyvitamin D concentrations (R(2) = 0.98, P = 0.007). CONCLUSIONS: Ensuring sufficient serum 25-hydroxyvitamin D concentrations might play an important role in decreasing the risk of bladder cancer. The serum 25 hydroxyvitamin D concentration >=74 nmol/L was associated with a 60% lower risk of bladder cancer incidence. PMID- 26822498 TI - A hiccup in holiday plans. PMID- 26822499 TI - Tetrandrine induces programmed cell death in human oral cancer CAL 27 cells through the reactive oxygen species production and caspase-dependent pathways and associated with beclin-1-induced cell autophagy. AB - Tetrandrine, a bisbenzylisoquinoline alkaloid, is extracted from the root of the Chinese herb Radix Stephania tetrandra S Moore. This compound has antitumor activity in different cancer cell types. In this study, the effects of tetrandrine on human oral cancer CAL 27 cells were examined. Results indicated that tetrandrine induced cytotoxic activity in CAL 27 cells. Effects were due to cell death by the induction of apoptosis and accompany with autophagy and these effects were concentration- and time-dependent manners. Tetrandrine induced apoptosis was accompanied by alterations in cell morphology, chromatin fragmentation, and caspase activation in CAL 27 cells. Tetrandrine treatment also induced intracellular accumulation of reactive oxygen species (ROS). The generation of ROS may play an important role in tetrandrine-induced apoptosis. Tetrandrine triggered LC3B expression and induced autophagy in CAL 27 cells. Tetrandrine induced apoptosis and autophagy were significantly attenuated by N acetylcysteine pretreatment that supports the involvement of ROS production. Tetrandrine induced cell death may act through caspase-dependent apoptosis with Beclin-1-induced autophagy in human oral cancer cells. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 329-343, 2017. PMID- 26822500 TI - Determinants of epoxy allergy in the construction industry: a case-control study. AB - BACKGROUND: Workers exposed to epoxy products are at risk of developing allergic contact dermatitis. OBJECTIVES: To compare workers throughout the German construction industry with and without skin allergy to epoxy resins, hardeners, and/or reactive diluents, and to investigate which determinants are related to the development of epoxy allergy. METHODS: A questionnaire was completed by 179 epoxy allergy cases, and 151 epoxy workers as controls. Crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by the use of backwards stepwise logistic regression analysis. A multiple imputation approach was used to deal with missing data. RESULTS: Epoxy allergy was associated with an unusually high level of exposure to epoxy products [OR 2.13 (95%CI: 1.01-4.51)], wearing short sleeves or short trousers [OR 2.38 (95%CI: 1.03-5.52)], and not always using the correct type of gloves [OR 2.12 (95%CI: 1.12-4.01)]. A monotonic increasing risk was found with increasing exposure hours per week [OR 1.72 (95%CI: 1.39-2.14)]. Not using skin cream was inversely associated with epoxy allergy [OR 0.22 (95%CI: 0.08-0.59)]. Years working with epoxy products were inversely associated with epoxy allergy [OR 0.41 (95%CI: 0.27-0.61) per 10-year increase], suggesting a healthy worker survivor effect. CONCLUSIONS: Occupational epoxy allergy may be prevented by improving occupational hygiene behaviour and personal protection. PMID- 26822501 TI - Slow-Growing Right Mandibular Mass. PMID- 26822502 TI - Overcoming Phase-Transfer Limitations in the Conversion of Lipophilic Oleo Compounds in Aqueous Media-A Thermomorphic Approach. AB - A new process concept has been developed for recycling transition-metal catalysts in the synthesis of moderately polar products via aqueous thermomorphic multicomponent solvent systems. This work focuses on the use of "green" solvents (1-butanol and water) in the hydroformylation of the bio-based substrate methyl 10-undecenoate. Following the successful development of a biphasic reaction system on the laboratory scale, the reaction was transferred to a continuously operated miniplant to demonstrate the robustness of this innovative recycling concept for homogenous catalysts. PMID- 26822503 TI - A prospective, randomised trial of different matching procedures for structured mentoring programmes in medical education. AB - BACKGROUND: Spontaneous formation of mentoring relationships can be seen as the gold standard in mentoring. Unfortunately, it happens very infrequently. The purpose of structured mentoring programmes is to facilitate the formation of mentoring relationships. This remains a challenging task, especially for large institutions. AIMS: We set out to investigate and compare three methods of matchmaking in the setting of our structured mentoring programme. In a prospective, randomised trial we compared personal matching (PM) by an experienced expert to two different electronic data processing (EDP)-supported matching procedures: "online algorithm" (OA) versus "online search" (OS). METHODS: PM was performed after structured interviews of prospective proteges by one founder of our mentoring programme. The OA provides students with a choice of 10 potential mentors based on comparison of online profiles. OS lets students filter and search through all available mentor profiles. One hundred and ninty medical students were randomised into the three groups. One year later, we evaluated the endpoints 1. "establishment of a mentoring relationship" and 2. "satisfaction with the mentoring relationship". Satisfaction with the mentoring relationship was assessed using Munich-Evaluation-of-Mentoring-Questionnaire (MEMeQ). RESULTS: One hundred sixty-five out of the 190 study participants found a mentor. With regards to endpoint one we found an advantage of PM compared to both EDP-supported matching procedures. There was no significant difference between OA and OS. Concerning endpoint two the differences between the investigated matching procedures were not significant. CONCLUSION: PM is superior as to the number of mentoring relationships formed per participating student compared to EDP-supported methods. In our data, there was no significant difference in the level of satisfaction. Considering the high investments associated with PM of mentors and proteges, EDP-supported matching procedures seem a viable compromise between effectiveness and efficiency especially for large-scale structured mentoring programmes in medical education. PMID- 26822504 TI - Superparamagnetic Reduced Graphene Oxide with Large Magnetoresistance: A Surface Modulation Strategy. AB - The graphene system is actively pursued in spintronics for its nontrivial sp electron magnetism and its potential for the flexible surface chemical tuning of magnetoelectronic functionality. The magnetoresistance (MR) of graphene can be effectively tuned under high magnetic fields at cryogenic temperatures, but it remains a challenge to achieve sensitive magnetoelectric response under ambient conditions. We report the use of surface modulation to realize superparamagnetism in reduced graphene oxide (rGO) with sensitive magnetic field response. The superparamagnetic rGO was obtained by a mild oxidation process to partially remove the thiol groups covalently bound to the carbon framework, which brings about large low-field negative MR at room temperature (-8.6 %, 500 Oe, 300 K). This strategy provides a new approach for optimizing the intrinsic magnetoelectric properties of two-dimensional materials. PMID- 26822505 TI - ToF-SIMS analysis of amyloid beta aggregation on different lipid membranes. AB - Amyloid beta (Abeta) peptides are considered to be strongly related to Alzheimer's disease. Abeta peptides form a beta-sheet structure on hard lipid membranes and it would aggregate to form amyloid fibrils, which are toxic to cells. However, the aggregation mechanism of Abeta is not fully understood. To evaluate the influence of the lipid membrane condition for Abeta aggregation, the adsorption forms of Abeta (1-40) on mixture membranes of lipid 1,2-dimyristoyl-sn glycero-3-phosphocholine (DMPC) and cholesterol beta-d-glucoside (beta-CG) were investigated by time-of-flight secondary ion mass spectrometry. As a result, Abeta adsorbed along the localized DMPC lipid on the mixture lipid membranes, whereas it was adsorbed homogeneously on the pure DMPC and beta-CG membranes. Moreover, amino acid fragments that mainly existed in the n-terminal of Abeta (1 40) peptide were strongly detected on the localized DMPC region. These results suggested that the Abeta was adsorbed along the localized DMPC lipid with a characteristic orientation. These findings suggest that the hardness of the membrane is very sensitive to coexisting materials and that surface hardness is important for aggregation of Abeta. PMID- 26822506 TI - Structural analysis of the outermost hair surface using TOF-SIMS with gas cluster ion beam sputtering. AB - A hair cuticle, which consists of flat overlapping scales that surround the hair fiber, protects inner tissues against external stimuli. The outermost surface of the cuticle is covered with a thin membrane containing proteins and lipids called the epicuticle. In a previous study, the authors conducted a depth profile analysis of a hair cuticle's amino acid composition to characterize its multilayer structure. Time-of-flight secondary ion mass spectrometry with a bismuth primary ion source was used in combination with the C60 sputtering technique for the analysis. It was confirmed that the lipids and cysteine-rich layer exist on the outermost cuticle surface, which is considered to be the epicuticle, though the detailed structure of the epicuticle has not been clarified. In this study, depth profile analysis of the cuticle surface was conducted using the argon gas cluster ion beam (Ar-GCIB) sputtering technique, in order to characterize the structure of the epicuticle. The shallow depth profile of the cuticle surface was investigated using an Ar-GCIB impact energy of 5 keV. Compared to the other amino acid peaks rich in the epicuticle, the decay of 18 methyleicosanic acid (18-MEA) thiolate peak was the fastest. This result suggests that the outermost surface of the hair is rich in 18-MEA. In conclusion, our results indicate that the outermost surfaces of cuticles have a multilayer (lipid and protein layers), which is consistent with the previously proposed structure. PMID- 26822507 TI - SLC20A2 Deficiency in Mice Leads to Elevated Phosphate Levels in Cerbrospinal Fluid and Glymphatic Pathway-Associated Arteriolar Calcification, and Recapitulates Human Idiopathic Basal Ganglia Calcification. AB - Idiopathic basal ganglia calcification is a brain calcification disorder that has been genetically linked to autosomal dominant mutations in the sodium-dependent phosphate co-transporter, SLC20A2. The mechanisms whereby deficiency of Slc20a2 leads to basal ganglion calcification are unknown. In the mouse brain, we found that Slc20a2 was expressed in tissues that produce and/or regulate cerebrospinal fluid, including choroid plexus, ependyma and arteriolar smooth muscle cells. Haploinsufficient Slc20a2 +/- mice developed age-dependent basal ganglia calcification that formed in glymphatic pathway-associated arterioles. Slc20a2 deficiency uncovered phosphate homeostasis dysregulation characterized by abnormally high cerebrospinal fluid phosphate levels and hydrocephalus, in addition to basal ganglia calcification. Slc20a2 siRNA knockdown in smooth muscle cells revealed increased susceptibility to high phosphate-induced calcification. These data suggested that loss of Slc20a2 led to dysregulated phosphate homeostasis and enhanced susceptibility of arteriolar smooth muscle cells to elevated phosphate-induced calcification. Together, dysregulated cerebrospinal fluid phosphate and enhanced smooth muscle cell susceptibility may predispose to glymphatic pathway-associated arteriolar calcification. PMID- 26822509 TI - Measures of Abdominal Adiposity and Risk of Stroke: A Dose-Response Meta-analysis of Prospective Studies. AB - OBJECTIVE: Waist circumference, waist-to-hip ratio and waist-to-height ratio, which are the indicators or measures of abdominal adiposity, have long been hypothesized to increase the risk of stroke; yet evidence accumulated till date is not conclusive. Here, we conducted a dose-response meta-analysis to summarize evidences of the association between these measures of abdominal adiposity and the risk of stroke. METHODS: PubMed and Web of Science databases were searched from inception to May 2015. Two investigators independently conducted the study selection and data extraction. Dose-response relationships were assessed by the generalized least squares trend estimation, while the summary effect estimates were evaluated by the use of fixed- or random-effect models. Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity and the robustness of the pooled estimation. Publication bias of the literature was evaluated using Begg's and Egger's test. RESULTS: Altogether 15 prospective cohort studies were identified in this study. The summary of relative risks (95% confidence intervals) of stroke for the highest versus the lowest categories was 1.28 (1.18-1.40) for waist circumference, 1.32 (1.21-1.44) for waist-to-hip ratio, and 1.49 (1.24-1.78) for waist-to-height ratio. For a 10 cm increase in waist circumference, the relative risk of stroke increased by 10%; for a 0.1-unit increase in waist-to-hip ratio, the relative risk increased by 16%; and for a 0.05-unit increase in waist-to-height ratio, the relative risk increased by 13%. There was evidence of a nonlinear association between waist-to hip ratio and stroke risk, Pnonlinearity=0.028. CONCLUSION: Findings from our meta-analysis indicated that waist circumference, waist-to-hip ratio, and waist to-height ratio were positively associated with the risk of stroke, particularly ischemic stroke. PMID- 26822510 TI - Nutrition in Chinese-Korean Children and Adolescents. AB - OBJECTIVE: To study the nutrition habits among Chinese-Korean children and adolescents in Yanbian Autonomous Prefecture, Jilin, China. METHODS: Data were obtained from the Chinese National Survey on Students' Constitution and Health in 1995, 2000, 2005, and 2010 for Chinese-Korean children and adolescents aged 7-18 years. The number of the subjects included was 4789, 4704, 5875, and 5315, respectively. RESULTS: The rate of the occurrence of stunting showed a declining trend from 1995 to 2010 (for boys: urban, 6.3%; rural, 12.7% in 1995 and 3.5% for both in 2010. For girls: urban, 7.8%; rural, 13.4% in 1995 and 4.2% and 5.5%, respectively, in 2010). Although the ratio of wasting did not show significant differences between the urban and rural children and adolescents in 1995, 2000, 2005, and 2010 respectively, the ratio of occurrence of overweight or obesity increased (for boys: urban, 7.3% and 1.3% in 1995, 17.6% and 12.9% in 2010; rural, 7.0% and 1.3% in 1995, 14.6% and 12.8% in 2010, respectively. For girls: urban, 8.1% and 1.0% in 1995, 17.3% and 8.6% in 2010; rural 5.7% and 0.7% in 1995, 16.4% and 7.4% in 2010, respectively). CONCLUSION: The ratio of malnutrition in children and adolescents in Chinese-Korean areas declined from 1995 to 2010, and the distinction in malnutrition between the urban and rural areas was negligible in 2010. Further, the ratio of overweight and obesity increased over this period. PMID- 26822508 TI - The Association of Maternal Body Composition and Dietary Intake with the Risk of Gestational Diabetes Mellitus during the Second Trimester in a Cohort of Chinese Pregnant Women. AB - OBJECTIVE: To investigate the association of maternal body composition and dietary intake with the risk of gestational diabetes mellitus (GDM). METHODS: A total 154 GDM subjects and 981 controls were enrolled in a prospective cohort study in 11 hospitals from May 20, 2012 to December 31, 2013. Bioelectrical impedance analysis and dietary surveys were used to determine body composition and to evaluate the intake of nutrients in subjects at 21-24 weeks' gestation (WG). Logistic regression analysis was applied to explore the relationships of maternal body composition and dietary intake with the risk of GDM morbidity. RESULTS: Age, pre-pregnant body weight (BW), and body mass index (BMI) were associated with increased risk of GDM. Fat mass (FM), fat mass percentage (FMP), extracellular water (ECW), BMI, BW, energy, protein, fat, and carbohydrates at 21 24 WG were associated with an increased risk of GDM. In contrast, fat free mass (FFM), muscular mass (MM), and intracellular water (ICW) were associated with a decreased risk of GDM. CONCLUSION: Maternal body composition and dietary intake during the second trimester of pregnancy were associated with the risk of GDM morbidity. PMID- 26822511 TI - Evaluation of A Single-reaction Method for Whole Genome Sequencing of Influenza A Virus using Next Generation Sequencing. AB - OBJECTIVE: To evaluate a single-reaction genome amplification method, the multisegment reverse transcription-PCR (M-RTPCR), for its sensitivity to full genome sequencing of influenza A virus, and the ability to differentiate mix subtype virus, using the next generation sequencing (NGS) platform. METHODS: Virus genome copy was quantified and serially diluted to different titers, followed by amplification with the M-RTPCR method and sequencing on the NGS platform. Furthermore, we manually mixed two subtype viruses to different titer rate and amplified the mixed virus with the M-RTPCR protocol, followed by whole genome sequencing on the NGS platform. We also used clinical samples to test the method performance. RESULTS: The M-RTPCR method obtained complete genome of testing virus at 125 copies/reaction and determined the virus subtype at titer of 25 copies/reaction. Moreover, the two subtypes in the mixed virus could be discriminated, even though these two virus copies differed by 200-fold using this amplification protocol. The sensitivity of this protocol we detected using virus RNA was also confirmed with clinical samples containing low-titer virus. CONCLUSION: The M-RTPCR is a robust and sensitive amplification method for whole genome sequencing of influenza A virus using NGS platform. PMID- 26822512 TI - Evaluation of Glycosaminoglycan in the Lumbar Disc Using Chemical Exchange Saturation Transfer MR at 3.0 Tesla: Reproducibility and Correlation with Disc Degeneration. AB - OBJECTIVE: This study aims to explore the clinical applicability and relevance of glycosaminoglycan Chemical Exchange Saturation Transfer (gagCEST) for intervertebral disc. METHODS: 25 subjects ranging in age from 24 yrs to 74 yrs were enrolled. gagCEST was acquired using a single-slice TSE sequence on a 3T. Saturation used a continuous rectangular RF pulse with B1=0.8 uT and a fixed duration time=1100 ms. Sagittal image was obtained firstly without saturation pulse, and then saturated images were acquired at 52 offsets ranging from +/ 0.125 to +/-7 parts per million (ppm). MR T2 relaxivity map was acquired at the identical location. Six subjects were scanned twice to assess scan-rescan reproducibility. RESULTS: GagCEST intraclass correlation coefficient (ICC) of six subjects was 0.759 for nucleus pulposus (NP) and 0.508 for annulus fibrosus (AF). Bland-Altman plots showed NP had a mean difference of 0.10% (95% limits of agreement: -3.02% to 3.22%); while that of AF was 0.34% (95% limits of agreement: -2.28% to 2.95%). For the 25 subjects, gag CEST in NP decreased as disc degeneration increased, with a similar trend to T2 relaxivity. Gag CEST of AF showed a better correlation with disc degeneration than T2 relaxivity. CONCLUSION: GagCEST in NP and AF decreased as disc degeneration increased, while gagCEST in AF showed a better correlation than T2 relaxivity. PMID- 26822513 TI - Proteomic Analysis of the Peritrophic Matrix from the Midgut of Third Instar Larvae, Musca domestica. AB - OBJECTIVE: To better comprehend the molecular structure and physiological function of the housefly larval peritrophic matrix (PM), a mass spectrometry approach was used to investigate the PM protein composition. METHODS: The PM was dissected from the midgut of the third instar larvae, and protein extracted from the PM was evaluated using SDS-PAGE. A 1D-PAGE lane containing all protein bands was cut from top to bottom, the proteins in-gel trypsinised and analysed via shotgun liquid chromatography- tandem mass spectrometry (LC-MS/MS). RESULTS: In total, 374 proteins, with molecular weights varying from 8.225 kD to 996.065 kD and isoelectric points ranging from 3.83 to 11.24 were successfully identified, most identified proteins were mainly related to immunity, digestion, nutrient metabolism and PM structure. Furthermore, many of these proteins were functionally associated with pattern binding, polysaccharide binding, structural constituent of peritrophic membrane and chitin binding, according to Gene Ontology annotation. CONCLUSION: The PM protein composition, which provides a basis for further functional investigations of the identified proteins, will be useful for understanding the housefly larval gut immune system and may help to identify potential targets and exploit new bioinsecticides. PMID- 26822514 TI - Potential Toxicological and Cardiopulmonary Effects of PM2.5 Exposure and Related Mortality: Findings of Recent Studies Published during 2003-2013. PMID- 26822515 TI - Poly(ADP-ribosyl)ation of Apoptosis Antagonizing Transcription Factor Involved in Hydroquinone-Induced DNA Damage Response. AB - The molecular mechanism of DNA damage induced by hydroquinone (HQ) remains unclear. Poly(ADP-ribose) polymerase-1 (PARP-1) usually works as a DNA damage sensor, and hence, it is possible that PARP-1 is involved in the DNA damage response induced by HQ. In TK6 cells treated with HQ, PARP activity as well as the expression of apoptosis antagonizing transcription factor (AATF), PARP-1, and phosphorylated H2AX (gamma-H2AX) were maximum at 0.5 h, 6 h, 3 h, and 3 h, respectively. To explore the detailed mechanisms underlying the prompt DNA repair reaction, the above indicators were investigated in PARP-1-silenced cells. PARP activity and expression of AATF and PARP-1 decreased to 36%, 32%, and 33%, respectively, in the cells; however, gamma-H2AX expression increased to 265%. Co immunoprecipitation (co-IP) assays were employed to determine whether PARP-1 and AATF formed protein complexes. The interaction between these proteins together with the results from IP assays and confocal microscopy indicated that poly(ADP ribosyl)ation (PARylation) regulated AATF expression. In conclusion, PARP-1 was involved in the DNA damage repair induced by HQ via increasing the accumulation of AATF through PARylation. PMID- 26822516 TI - Beneficial effects of dietary docosahexaenoic acid intervention on cognitive function and mental health of the oldest elderly in Japanese care facilities and nursing homes. AB - AIM: We examined the effects of the administration of docosahexaenoic acid (DHA) enriched meals on cognitive function in the oldest elderly with cognitive impairment, such as dementia, living in nursing homes, and on the improvement in caregiver burden at aging agencies. METHODS: Participants in elderly care facilities and nursing homes (n = 75; 88.5 +/- 0.6 years) were randomized in active and placebo groups. The active group had family-style meals containing an additional 1720 mg of docosahexaenoic acid per day for 12 months. At baseline, and after 6 and 12 months of intervention, cognitive function was assessed using Hasegawa's Dementia Scale-Revised and the Mini-Mental State Examination; mental health condition was assessed with the Apathy scale and the Zung Self-Rating Depression Scale; caregiver burden was evaluated using Zarit Burden Interview scores; and participants' serum biochemical factors were measured. RESULTS: The participants were suggested to have dementia. After 12 months, the mean change in Mini-Mental State Examination subitem "Registration" score from baseline to month 12 showed a tendency to be greater in the active group than that in the placebo group. Mean changes in the Apathy scale from baseline to month 12 were less, and the changes in the Zung Self-Rating Depression Scale and the total Zarit Burden Interview scores showed a tendency to be lower in the active group than in the placebo group, respectively. CONCLUSION: These results suggest that docosahexaenoic acid-enriched meals protect against age-related cognitive decline, and also improve apathy and caregiver burden for the oldest-elderly Japanese with cognitive impairment, such as dementia. Geriatr Gerontol Int 2017; 17: 330-337. PMID- 26822518 TI - Comparison of FT-NIR Spectroscopy and ELISA for Detection of Adulteration of Goat Cheeses with Cow's Milk. AB - This study investigated the ability of two methods to detect adulteration of goat cheeses via the addition of cow's milk, with a negligible effect on the raw materials. Cheeses were produced from a mixture of goat's and cow's milk and were then analyzed by Fourier transform near-IR (FT-NIR) spectroscopy and competitive ELISA. The cheese spectra were scanned in the spectroscope in reflectance mode on an integrating sphere at 80 scans and a resolution of 4 cm(-1). The spectra were evaluated via discriminant analysis, and a calibration was created via a partial least-squares algorithm to quantify the cow's milk admixture. A correlation coefficient of R = 0.999 was reached with a standard error of calibration of 0.0407. The results were statistically processed to a median value via a t-test. Adulteration detection by the ELISA method was performed using a commercial Milk Fraud/Bovine ELISA kit. It was found that the FT-NIR spectroscopy method is capable of detecting an admixture of cow's milk in goat cheese as small as 1%. The ELISA method did not return satisfactory results for the detection of adulteration with cow's milk. PMID- 26822519 TI - Small molecule diselenide additives for in vitro oxidative protein folding. AB - The in vitro oxidative folding of disulfide-rich proteins can be challenging. Here we show a new class of small molecule diselenides, which can be easily prepared from inexpensive starting materials, used to enhance oxidative protein folding. These compounds were tested on a model protein, bovine pancreatic trypsin inhibitor. Two of the tested diselenides showed considerable improvement over glutathione and were on par with the previously described selenoglutathione. PMID- 26822517 TI - Norovirus in symptomatic and asymptomatic individuals: cytokines and viral shedding. AB - Noroviruses (NoV) are the most common cause of epidemic gastroenteritis world wide. NoV infections are often asymptomatic, although individuals still shed large amounts of NoV in their stool. Understanding the differences between asymptomatic and symptomatic individuals would help in elucidating mechanisms of NoV pathogenesis. Our goal was to compare the serum cytokine responses and faecal viral RNA titres of asymptomatic and symptomatic NoV-infected individuals. We tested serum samples from infected subjects (n = 26; 19 symptomatic, seven asymptomatic) from two human challenge studies of GI.1 NoV for 16 cytokines. Samples from prechallenge and days 1-4 post-challenge were tested for these cytokines. Cytokine levels were compared to stool NoV RNA titres quantified previously by reverse transcription-polymerase chain reaction (RT-qPCR). While both symptomatic and asymptomatic groups had similar patterns of cytokine responses, the symptomatic group generally exhibited a greater elevation of T helper type 1 (Th1) and Th2 cytokines and IL-8 post-challenge compared to the asymptomatic group (all P < 0.01). Daily viral RNA titre was associated positively with daily IL-6 concentration and negatively with daily IL-12p40 concentration (all P < 0.05). Symptoms were not associated significantly with daily viral RNA titre, duration of viral shedding or cumulative shedding. Symptomatic individuals, compared to asymptomatic, have greater immune system activation, as measured by serum cytokines, but they do not have greater viral burden, as measured by titre and shedding, suggesting that symptoms may be immune mediated in NoV infection. PMID- 26822520 TI - Enhancement of Photo-Oxidation Activities Depending on Structural Distortion of Fe-Doped TiO2 Nanoparticles. AB - To design a high-performance photocatalytic system with TiO2, it is necessary to reduce the bandgap and enhance the absorption efficiency. The reduction of the bandgap to the visible range was investigated with reference to the surface distortion of anatase TiO2 nanoparticles induced by varying Fe doping concentrations. Fe-doped TiO2 nanoparticles (Fe@TiO2) were synthesized by a hydrothermal method and analyzed by various surface analysis techniques such as transmission electron microscopy, Raman spectroscopy, X-ray diffraction, scanning transmission X-ray microscopy, and high-resolution photoemission spectroscopy. We observed that Fe doping over 5 wt.% gave rise to a distorted structure, i.e., Fe2Ti3O9, indicating numerous Ti(3+) and oxygen-vacancy sites. The Ti(3+) sites act as electron trap sites to deliver the electron to O2 as well as introduce the dopant level inside the bandgap, resulting in a significant increase in the photocatalytic oxidation reaction of thiol (-SH) of 2-aminothiophenol to sulfonic acid (-SO3H) under ultraviolet and visible light illumination. PMID- 26822521 TI - Advances in brain barriers and brain fluid research and news from Fluids and Barriers of the CNS. AB - Research into brain barriers and brain fluids has been advancing rapidly in recent years. This editorial aims to highlight some of the advances that have improved our understanding of this complex subject. It also brings you news of developments for Fluids and Barriers of the CNS including a new affiliation between the journal and the International Society for Hydrocephalus and CSF disorders. PMID- 26822523 TI - Endoscopic ultrasound of pancreatic duct ascariasis. PMID- 26822522 TI - Revisiting typhoid fever surveillance in low and middle income countries: lessons from systematic literature review of population-based longitudinal studies. AB - BACKGROUND: The control of typhoid fever being an important public health concern in low and middle income countries, improving typhoid surveillance will help in planning and implementing typhoid control activities such as deployment of new generation Vi conjugate typhoid vaccines. METHODS: We conducted a systematic literature review of longitudinal population-based blood culture-confirmed typhoid fever studies from low and middle income countries published from 1(st) January 1990 to 31(st) December 2013. We quantitatively summarized typhoid fever incidence rates and qualitatively reviewed study methodology that could have influenced rate estimates. We used meta-analysis approach based on random effects model in summarizing the hospitalization rates. RESULTS: Twenty-two papers presented longitudinal population-based and blood culture-confirmed typhoid fever incidence estimates from 20 distinct sites in low and middle income countries. The reported incidence and hospitalizations rates were heterogeneous as well as the study methodology across the sites. We elucidated how the incidence rates were underestimated in published studies. We summarized six categories of under estimation biases observed in these studies and presented potential solutions. CONCLUSIONS: Published longitudinal typhoid fever studies in low and middle income countries are geographically clustered and the methodology employed has a potential for underestimation. Future studies should account for these limitations. PMID- 26822524 TI - Optimizing the Intralayer and Interlayer Compatibility for High-Efficiency Blue Thermally Activated Delayed Fluorescence Diodes. AB - A series of phosphine oxide hosts, 4,6-bis(diphenylphosphoryl) dibenzothiophene (DBTDPO) and 4- diphenylphosphoryldibenzothiophene (DBTSPO), and electron transporting materials (ETM), 2-(diphenylphosphoryl)dibenzothiophene sulfone (2DBSOSPO), 3-(diphenylphosphoryl)dibenzothiophene sulfone (3DBSOSPO) and 4 (diphenylphosphoryl)dibenzothiophene sulfone (4DBSOSPO) were developed to support blue thermally activated delayed fluorescence (TADF) devices with high performance through optimizing intralayer and interlayer compatibility of emissive layers. On the basis of the triplet energy of ~3.0 eV for the hosts and ETMs, excitons can be effectively confined on DMAC-DPS. Compared to DBTSPO, DBTDPO can support the excellent distribution uniformity to blue TADF dye bis[4 (9,9-dimethyl-9,10-dihydroacridine) phenyl] sulfone (DMAC-DPS), owing to their configuration similarity; while 3DBSOSPO and 4DBSOSPO are superior in compatibility with the hosts due to the similar molecular polarity or configuration. Through adjusting the molecular configuration, the electrical performance of ETMs can be feasibly tuned, including the excellent electron mobility (MUe) by the order of 10(-3) cm(2) V(-1) s(-1). As the result, DBTDPO and 4DBSOSPO endowed their four-layer blue TADF devices with the maximum current efficiency of 33.5 cd A(-1) and the maximum external quantum efficiency more than 17%, which are impressive among the best blue TADF devices. It is showed that intralayer compatibility determines the maximum efficiencies, while interlayer compatibility influences efficiency stability. PMID- 26822526 TI - An experimental proposal to test the physical effect of the vector potential. AB - There are two interpretations of the Aharonov-Bohm (A-B) effect. One interpretation asserts that the A-B effect demonstrates that the vector potential is a physical reality that can result in the phase shift of a moving charge in quantum mechanics. The other interpretation asserts that the phase shift of the moving charge results from the interaction energy between the electromagnetic field of the moving charge and external electromagnetic fields. This paper briefly reviews these two interpretations and analyzes their differences. In addition, a new experimental scheme is proposed to determine which interpretation is correct. PMID- 26822527 TI - A robust and reproducible procedure for cross-linking thermoset polymers using molecular simulation. AB - Molecular simulation can provide valuable guidance in establishing clear links between structure and function to enable the design of new polymer-based materials. However, molecular simulation of thermoset polymers in particular, such as epoxies, present specific challenges, chiefly in the credible preparation of polymerised samples. Despite this need, a comprehensive, reproducible and robust process for accomplishing this using molecular simulation is still lacking. Here, we introduce a clear and reproducible cross-linking protocol to reliably generate three dimensional epoxy cross-linked polymer structures for use in molecular simulations. This protocol is sufficiently detailed to allow complete reproduction of our results, and is applicable to any general thermoset polymer. Amongst our developments, key features include a reproducible procedure for calculation of partial atomic charges, a reliable process for generating and validating an equilibrated liquid precursor mixture, and establishment of a novel, robust and reproducible protocol for generating the three-dimensional cross-linked solid polymer. We use these structures as input to subsequent molecular dynamics simulations to calculate a range thermo-mechanical properties, which compare favourably with experimental data. Our general protocol provides a benchmark for the process of simulating epoxy polymers, and can be readily translated to prepare and model epoxy samples that are dynamically cross-linked in the presence of surfaces and nanostructures. PMID- 26822525 TI - A powerful score-based test statistic for detecting gene-gene co-association. AB - BACKGROUND: The genetic variants identified by Genome-wide association study (GWAS) can only account for a small proportion of the total heritability for complex disease. The existence of gene-gene joint effects which contains the main effects and their co-association is one of the possible explanations for the "missing heritability" problems. Gene-gene co-association refers to the extent to which the joint effects of two genes differ from the main effects, not only due to the traditional interaction under nearly independent condition but the correlation between genes. Generally, genes tend to work collaboratively within specific pathway or network contributing to the disease and the specific disease associated locus will often be highly correlated (e.g. single nucleotide polymorphisms (SNPs) in linkage disequilibrium). Therefore, we proposed a novel score-based statistic (SBS) as a gene-based method for detecting gene-gene co association. RESULTS: Various simulations illustrate that, under different sample sizes, marginal effects of causal SNPs and co-association levels, the proposed SBS has the better performance than other existed methods including single SNP based and principle component analysis (PCA)-based logistic regression model, the statistics based on canonical correlations (CCU), kernel canonical correlation analysis (KCCU), partial least squares path modeling (PLSPM) and delta-square (delta (2)) statistic. The real data analysis of rheumatoid arthritis (RA) further confirmed its advantages in practice. CONCLUSIONS: SBS is a powerful and efficient gene-based method for detecting gene-gene co-association. PMID- 26822528 TI - Oncologists' Role in Patient Fertility Care: A Call to Action. PMID- 26822529 TI - Flexible and free-standing ternary Cd2GeO4 nanowire/graphene oxide/CNT nanocomposite film with improved lithium-ion battery performance. AB - To realize flexible lithium-ion batteries (LIBs), the design of flexible electrode/current collector materials with high mechanical flexibility, superior conductivity and excellent electrochemical performance and electrical stability are highly desirable. In this work, we developed a new ternary Cd2GeO4 nanowire/graphene oxide/carbon nanotube nanocomposite (Cd2GeO4 NW/GO/CNT) film electrode. Benefiting from the efficient combination of GO and Cd2GeO4 NWs, our Cd2GeO4 NW/GO/CNT composite film exhibits a capacity of 784 mA h g(-1) after 30 cycles at 200 mA g(-1), which is 2.7 times higher than that of Cd2GeO4 NW/CNT film (290 mA h g(-1)). At a higher rate of 400 mA g(-1) and 1 A g(-1), the Cd2GeO4 NW/GO/CNT film delivers a stable capacity of 617 and 397 mA h g(-1), respectively. Even at 2.5 A g(-1), it still exhibits a high rate capacity of 180 mA h g(-1). The flexible Cd2GeO4 NW/GO/CNT film clearly demonstrates good cycling stability and rate performance for anode materials in LIBs. This route may be extended to design other flexible free-standing metal germanate nanocomposite anode materials. PMID- 26822530 TI - Osthole Alleviates Bleomycin-Induced Pulmonary Fibrosis via Modulating Angiotensin-Converting Enzyme 2/Angiotensin-(1-7) Axis and Decreasing Inflammation Responses in Rats. AB - Studies have shown that angiotensin-converting enzyme 2 (ACE2) plays modulating roles in lung pathophysiology, including pulmonary fibrosis (PF) and acute lung injury. Pulmonary fibrosis is a common complication in these interstitial lung diseases, and PF always has a poor prognosis and short survival. To date, there are few promising methods for treating PF, and they are invariably accompanied by severe side effects. Recent studies have showed that the traditional Chinese herbal extract, osthole, had beneficial effects on lipopolysaccharide (LPS) induced acute lung injury (ALI) via an ACE2 pathway. Here we further investigated the protective effects of osthole on bleomycin induced pulmonary fibrosis and attempted to determine the underlying mechanism. PF mode rats were induced by bleomycin (BLM) and then subsequently administered osthole. Histopathological analyses were employed to identify PF changes. The results showed that BLM resulted in severe PF and diffuse lung inflammation, together with significant elevation of inflammatory factors and a marked increase in expression of angiotensin II (ANG II) and transforming growth factor-beta 1 (TGF-beta1). ACE2 and angiotensin-(1-7) [ANG-(1-7)] were both greatly reduced after BLM administration. Meanwhile, osthole treatment attenuated BLM induced PF and inflammation, decreased the expression of these inflammatory mediators, ANG II, and TGF-beta1, and reversed ACE2 and ANG-(1-7) production in rat lungs. We conclude that osthole may exert beneficial effects on BLM induced PF in rats, perhaps via modulating the ACE2/ANG-(1-7) axis and inhibiting lung inflammation pathways. PMID- 26822531 TI - The Optimal Duration of PTH(1-34) Infusion Is One Hour per Day to Increase Bone Mass in Rats. AB - Parathyroid hormone (PTH) is a potential medicine for osteoporosis, and subcutaneous (s.c.) PTH treatment enhances bone mass; however, continuous infusion of PTH elicits bone resorption and induces bone loss. To clarify this contradictory phenomenon, we examined bone markers and bone mass in rats to assess the optimal duration of PTH(1-34) infusion. Continuous infusion of PTH at 1 ug/kg/h (Css, steady-state concentration ca. 300 pg/mL) for 1-4 h clearly stimulated the expression both of bone formation-related genes (c-fos, Wnt4, EphrinB2) and of bone resorption-related genes (tnfsf11, tnfsf11b, encoding receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG)), but s.c. treatment stimulated these genes only 1-h after the injection. Rats were treated with 1-, 2-, or 4-h infusions of PTH daily using a totally implanted catheter system, and the femoral bone mineral density (BMD) was measured at 4 weeks. The 1-h infusion of PTH significantly stimulated serum bone formation markers (procollagen I N-terminal propeptide (PINP) and osteocalcin) on day 14 and femoral BMD at 2 and 4 weeks, but the 4-h infusion of PTH did not enhance BMD. Since the 4-h infusion increased the levels of both the bone formation markers and a bone resorption marker (urinary C-terminal telopeptide of type 1 collagen (CTx)), the increased bone resorption may predominate over bone formation. The intermittent elevation of plasma PTH to 300 pg/mL for 1-h each day is optimal for increasing bone mass in rats. In osteoporosis therapy in human, using the optimal duration for the clinical dose of PTH may selectively stimulate bone formation. PMID- 26822532 TI - Materials vigilance and traceability. AB - Patient safety requires speedy detection of any medical device malfunction; this is known as "materials vigilance". It entails the need to be able to trace back the life-long pathway of a device; this is "traceability". European regulations enact free circulation of medical devices throughout the European Union, with each member state being responsible for safety within its own territory. Medical devices are divided into 3 categories of increasing risk. CE marking mandatory for medical devices distributed within the EU, and count as market authorizations. They are delivered with 5-year validity by what is known as a "notified body". Health authorities are responsible for monitoring the market and any incidents. New regulations are presently being drawn up to improve efficiency and transparency. Materials vigilance is founded on mandatory declaration of medical device incidents. At local level, it comprises local reporters responsible for informing the National Health Products Safety Agency (Agence nationale de securite du medicament et des produits de sante [ANSM]) of any incidents and taking all necessary precautions. At national level, the ANSM assesses the safety, efficacy and quality of healthcare products; it centralizes and assesses materials vigilance reports and takes the requisite decisions. Materials vigilance is further organized at the European and international levels, to harmonize legislation regarding medical devices. Traceability is intended to rapidly identify medical device bearers in case of product recall. Each center is to organize the traceability of its devices; manufacturers' obligation of traceability ceases with the healthcare establishment or user. CE marking involves strict labeling rules to ensure safety of use. A change in the organization of traceability is presently underway, in the form of international Unique Device Identifiers, with harmonized label data, barcodes and standardized terminology. A European and later international database will be set up. The objective is to make Unique Device Identifiers mandatory within the EU by 2017. PMID- 26822533 TI - Defective DNA single-strand break repair is responsible for senescence and neoplastic escape of epithelial cells. AB - The main characteristic of senescence is its stability which relies on the persistence of DNA damage. We show that unlike fibroblasts, senescent epithelial cells do not activate an ATM-or ATR-dependent DNA damage response (DDR), but accumulate oxidative-stress-induced DNA single-strand breaks (SSBs). These breaks remain unrepaired because of a decrease in PARP1 expression and activity. This leads to the formation of abnormally large and persistent XRCC1 foci that engage a signalling cascade involving the p38MAPK and leading to p16 upregulation and cell cycle arrest. Importantly, the default in SSB repair also leads to the emergence of post-senescent transformed and mutated precancerous cells. In human aged skin, XRCC1 foci accumulate in the epidermal cells in correlation with a decline of PARP1, whereas DDR foci accumulate mainly in dermal fibroblasts. These findings point SSBs as a DNA damage encountered by epithelial cells with aging which could fuel the very first steps of carcinogenesis. PMID- 26822535 TI - Improving encoding strategies as a function of test knowledge and experience. AB - Information that is produced or generated during learning is better remembered than information that is passively read, a phenomenon known as the generation effect. Prior research by deWinstanley and Bjork (Memory & Cognition, 32, 945 955, 2004) has shown that learners, after experiencing the memorial benefits of generation in the context of a fill-in-the-blank test following the study of a text passage containing both to-be-read and to-be-generated items, become more effective encoders of to-be-read items on a second passage, thus eliminating the generation effect on a subsequent memory test. Current explanations of this phenomenon assume that learners need to actually experience the generation advantage on the test of the first passage to become more effective encoders of to-be-read items on the second passage. The results of the present research, however, suggest otherwise. Although experiencing a test of the first passage does appear to be critical for leading participants to become better encoders on the second passage, experiencing a generation advantage on the test for the first passage is not. More generally, these results shine new light on the generation effect as well as how and why taking tests has the potential to improve subsequent learning. PMID- 26822534 TI - MicroRNA-224 sustains Wnt/beta-catenin signaling and promotes aggressive phenotype of colorectal cancer. AB - BACKGROUND: Growing evidence suggests that Wnt/beta-catenin pathway plays an important role in CRC development, progression and metastasis. Aberrant miR-224 expression has been reported in CRC. However, the mechanism of miR-224 promotes both proliferation and metastatic ability largely remains unclear. METHODS: Real time PCR was used to quantify miR-224 expression. Luciferase reporter assays were conducted to confirm the activity of Wnt/beta-catenin pathway and target gene associations, and immunofluorescence staining assay was performed to observe the nuclear translocation of beta-catenin. Bioinformatics analysis combined with in vivo and vitro functional assays showed the potential target genes, GSK3beta and SFRP2, of miR-224. Specimens from forty patients with CRC were analyzed for the expression of miR-224 and the relationship with GSK3beta/SFRP2 by real-time PCR and western blot. RESULTS: Bioinformatics and cell luciferase function studies verified the direct regulation of miR-224 on the 3'-UTR of the GSK3beta and SFRP2 genes, which leads to the activation of Wnt/beta-catenin signaling and the nuclear translocation of beta-catenin. In addition, knockdown of miR-224 significantly recovered the expression of GSK3beta and SFRP2 and attenuated Wnt/beta-catenin-mediated cell metastasis and proliferation. The ectopic upregulation of miR-224 dramatically inhibited the expression of GSK3beta/SFRP2 and enhanced CRC proliferation and invasion. CONCLUSION: Our research showed mechanistic links between miR-224 and Wnt/beta-catenin in the pathogenesis of CRC through modulation of GSK3beta and SFRP2. PMID- 26822536 TI - Structural basis for the recognition of two consecutive mutually interacting DPF motifs by the SGIP1 MU homology domain. AB - FCHo1, FCHo2, and SGIP1 are key regulators of clathrin-mediated endocytosis. Their MU homology domains (MUHDs) interact with the C-terminal region of an endocytic scaffold protein, Eps15, containing fifteen Asp-Pro-Phe (DPF) motifs. Here, we show that the high-affinity MUHD-binding site in Eps15 is a region encompassing six consecutive DPF motifs, while the minimal MUHD-binding unit is two consecutive DPF motifs. We present the crystal structures of the SGIP1 MUHD in complex with peptides containing two DPF motifs. The peptides bind to a novel ligand-binding site of the MUHD, which is distinct from those of other distantly related MUHD-containing proteins. The two DPF motifs, which adopt three dimensional structures stabilized by sequence-specific intramotif and intermotif interactions, are extensively recognized by the MUHD and are both required for binding. Thus, consecutive and singly scattered DPF motifs play distinct roles in MUHD binding. PMID- 26822537 TI - Combining self-management cues with incentives to promote interdental cleaning among Indian periodontal disease outpatients. AB - BACKGROUND: Periodontal disease is a significant public health issue worldwide. Motivational techniques in combination with financial incentives are shown to lead to effective behavior change. The current study sought to examine whether a brief oral health promotion program (self-management cues that were based on self efficacy and self-regulatory skills) in combination with an incentive (free dental treatment) would make a difference in the adoption of regular dental flossing in a population of Indian periodontal disease outpatients. METHODS: One hundred and twelve participants (n = 55 oral health promotion intervention group; n = 57 control group) were assigned to the intervention (self-management cues + incentive) or control groups, and follow-up assessments were performed three weeks later. Flossing frequency, behavioral intentions, and perceived self efficacy served as dependent variables. Data were analyzed with mixed models, ANCOVAs, and path analyses. RESULTS: The intervention yielded effects on flossing frequency (p < 0.01) and flossing intentions (p < 0.01) at follow-up. Women developed stronger intentions than men. Moreover, by path analysis a sequential mediation chain was found that demonstrated an indirect effect of the intervention on flossing via self-efficacy and intentions: the intervention predicted changes in self-efficacy which, in turn, were associated with changes in intentions, predicting flossing frequency at follow up, while controlling for baseline behavior, gender, and age. CONCLUSIONS: Combining incentives with minimal self-management cues has been found effective in improving interdental cleaning intentions and habits in periodontal disease patients, and the facilitating role of dental self-efficacy has been demonstrated. PMID- 26822538 TI - Effects of diet containing flaxseed flour (Linum usitatissimum) on body adiposity and bone health in young male rats. AB - Flaxseed flour has been described as an excellent alpha-linolenic acid source. This study was designed to evaluate the effects of flaxseed flour on body adiposity and bone health in rats fed a flaxseed flour diet during lactation until 90 days. At birth, male Wistar rats were randomly assigned to control (C) and experimental (FF) groups, whose dams were treated with a control or flaxseed flour diet, respectively, during lactation. At 21 days, pups were weaned and fed a control and experimental diet until 90 days. Food intake, body mass and length were evaluated during a 21-90 day period. At 90 days, composition by dual-energy X-ray absorptiometry, serum hormonal profile, intra-abdominal fat mass, and lumbar vertebra and femur analyses was determined. Differences were deemed significant at p < 0.05. The FF group displayed the following (P < 0.05): a higher total lean mass (+7%), a lower total (-16%) and intra-abdominal (-24%) fat mass, a smaller adipocyte area (-30%), a higher femoral mass (+5%), bone mineral density (+5%) and radiodensity (+20%), and a higher maximum force (+10%) and breaking strength (+11%). The flaxseed flour diet displayed functional properties related to body growth maintenance associated with a lower risk of developing metabolic alterations, obesity and bone fragility. PMID- 26822539 TI - Improving nanoparticle diffusion through tumor collagen matrix by photo-thermal gold nanorods. AB - Collagen (I) impairs the targeting of nanoparticles to tumor cells by obstructing their diffusion inside dense tumor interstitial matrix. This potentially makes large nanoparticles (>50 nm) reside near the tumor vessels and thereby compromises their functionality. Here we propose a strategy to locally improve nanoparticle transport inside collagen (I) component of the tumor tissue. We first used heat generating gold nanorods to alter collagen (I) matrix by local temperature elevation. We then explored this impact on the transport of 50 nm and 120 nm inorganic nanoparticles inside collagen (I). We demonstrated an increase in average diffusivity of 50 nm and 120 nm in the denatured collagen (I) by ~14 and ~21 fold, respectively, compared to intact untreated collagen (I) matrix. This study shows how nanoparticle-mediated hyperthermia inside tumor tissue can improve the transport of large nanoparticles through collagen (I) matrix. The ability to increase nanoparticles diffusion inside tumor stroma allows their targeting or other functionalities to take effect, thereby significantly improving cancer therapeutic or diagnostic outcome. PMID- 26822540 TI - Integrating ecosystem services into crop protection and pest management: Case study with the soil fumigant 1,3-dichloropropene and its use in tomato production in Italy. AB - Ecosystems provide the conditions for producing food, regulating water, and providing wildlife habitats; these, among others, are known as ecosystem services (ESs). Food production is both economically and culturally important to southern European farmers, particularly in Italy where farmers grow flavorsome tomatoes with passion and pride. Growers rely on pesticides for crop protection, the potential environmental impact of which is often questioned by regulators and other stakeholders. The European regulatory system for the approval of pesticides includes a thorough evaluation of risks to the environment and is designed to be protective of ecosystems. The consideration of ESs in environmental decision making is a growing trend, and the present case study provides an example of how ESs evaluation could be used to enhance agricultural practices and regulatory policy for crop protection. By attacking plant roots, nematodes may affect the growth and yield of fruit and vegetable crops, and the income earned by farmers at harvest time. Available solutions include chemical treatments such as 1,3 dichloropropene (1,3-D), physical treatments (solarization), and biological treatments (biofumigation). In order to characterize the risks and benefits associated with the use of 1,3-D in crop protection, ESs and socioeconomic analyses were applied to its use in the control of nematodes in tomato cultivation in southern Italy. The present study confirmed the benefits of 1,3-D to tomato production in Italy, with significant positive effects on production yields and farm income when compared to limited and transient potential impacts on services such as soil function. It was confirmed that 1,3-D allows farm income to be maintained and secures tomato production in these regions for the future. Integr Environ Assess Manag 2016;12:801-810. (c) 2016 SETAC. PMID- 26822541 TI - Prevalence rate and clinical characteristics of esophageal ectopic sebaceous glands in asymptomatic health screen examinees. AB - Ectopic sebaceous glands in the esophagus have rarely been reported and, thus, represent an obscure medical condition. The aim of this study is to identify the prevalence rate and clinical characteristics of this lesion in an asymptomatic population. We prospectively enrolled health screen examinees who underwent esophagogastroduodenoscopy for gastric cancer screening. An esophageal biopsy was performed in the cases in which esophageal ectopic sebaceous glands were suspected. The general characteristics of the examinees were analyzed based on their medical records. A total of 9989 examinees were enrolled, and five examinees were diagnosed with esophageal ectopic sebaceous glands between December 2012 and June 2014. The endoscopic findings of the esophageal ectopic sebaceous glands indicated multiple yellowish patches or papules, which varied in size. The histopathological findings indicated several lobulated sebaceous glands in the squamous epithelium with inflammatory infiltration. The follow-up endoscopic findings indicated that there was no grossly discernible change. In conclusion, esophageal ectopic sebaceous glands are present in 0.05% of asymptomatic subjects. This lesion is thought to be benign and is not related to clinical symptoms. Therefore, esophageal ectopic sebaceous glands do not require further treatment or follow-up, which makes endoscopists free from active efforts for differential diagnosis with other malignant diseases. PMID- 26822542 TI - Understanding the physiology of mindfulness: aortic hemodynamics and heart rate variability. AB - Data were collected to examine autonomic and hemodynamic cardiovascular modulation underlying mindfulness from two independent samples. An initial sample (N = 185) underwent laboratory assessments of central aortic blood pressure and myocardial functioning to investigated the association between mindfulness and cardiac functioning. Controlling for religiosity, mindfulness demonstrated a strong negative relationship with myocardial oxygen consumption and left ventricular work but not heart rate or blood pressure. A second sample (N = 124) underwent a brief (15 min) mindfulness inducing intervention to examine the influence of mindfulness on cardiovascular autonomic modulation via blood pressure variability and heart rate variability. The intervention had a strong positive effect on cardiovascular modulation by decreasing cardiac sympathovagal tone, vasomotor tone, vascular resistance and ventricular workload. This research establishes a link between mindfulness and cardiovascular functioning via correlational and experimental methodologies in samples of mostly female undergraduates. Future directions for research are outlined. PMID- 26822543 TI - Gyrodactylus spp. diversity in native and introduced minnow (Phoxinus phoxinus) populations: no support for "the enemy release" hypothesis. AB - BACKGROUND: Translocation of native species and introduction of non-native species are potentially harmful to the existing biota by introducing e.g. diseases, parasites and organisms that may negatively affect the native species. The enemy release hypothesis states that parasite species will be lost from host populations when the host is introduced into new environments. METHODS: We tested the enemy release hypothesis by comparing 14 native and 29 introduced minnow (Phoxinus phoxinus) populations in Norway with regard to the ectoparasitic Gyrodactylus species community and load (on caudal fin). Here, we used a nominal logistic regression on presence/absence of Gyrodactylus spp. and a generalized linear model on the summed number of Gyrodactylus spp. on infected populations, with individual minnow heterozygosity (based on 11 microsatellites) as a covariate. In addition, a sample-based rarefaction analysis was used to test if the Gyrodactylus-species specific load differed between native and introduced minnow populations. An analysis of molecular variance was performed to test for hierarchical population structure between the two groups and to test for signals of population bottlenecks the two-phase model in the Wilcoxon signed-rank test was used. To test for demographic population expansion events in the introduced minnow population, we used the kg-test under a stepwise mutation model. RESULTS: The native and introduced minnow populations had similar species compositions of Gyrodactylus, lending no support to the enemy release hypothesis. The two minnow groups did not differ in the likelihood of being infected with Gyrodactylus spp. Considering only infected minnow populations it was evident that native populations had a significantly higher mean abundance of Gyrodactylus spp. than introduced populations. The results showed that homozygotic minnows had a higher Gyrodactylus spp. infection than more heterozygotic hosts. Using only infected individuals, the two minnow groups did not differ in their mean number of Gyrodactylus spp. However, a similar negative association between heterozygosity and abundance was observed in the native and introduced group. There was no evidence for demographic bottlenecks in the minnow populations, implying that introduced populations retained a high degree of genetic variation, indicating that the number of introduced minnows may have been large or that introductions have been happening repeatedly. This could partly explain the similar species composition of Gyrodactylus in the native and introduced minnow populations. CONCLUSIONS: In this study it was observed that native and introduced minnow populations did not differ in their species community of Gyrodactylus spp., lending no support to the enemy release hypothesis. A negative association between individual minnow host heterozygosity and the number of Gyrodactylus spp. was detected. Our results suggest that the enemy release hypothesis does not necessarily limit fish parasite dispersal, further emphasizing the importance of invasive fish species dispersal control. PMID- 26822544 TI - Diversity and severity of adverse reactions to quinine: A systematic review. AB - Quinine is a common cause of drug-induced thrombocytopenia and the most common cause of drug-induced thrombotic microangiopathy. Other quinine-induced systemic disorders have been described. To understand the complete clinical spectrum of adverse reactions to quinine we searched 11 databases for articles that provided sufficient data to allow evaluation of levels of evidence supporting a causal association with quinine. Three reviewers independently determined the levels of evidence, including both immune-mediated and toxic adverse reactions. The principal focus of this review was on acute, immune-mediated reactions. The source of quinine exposure, the involved organ systems, the severity of the adverse reactions, and patient outcomes were documented. One hundred-fourteen articles described 142 patients with definite or probable evidence for a causal association of quinine with acute, immune-mediated reactions. These reactions included chills, fever, hypotension, painful acral cyanosis, disseminated intravascular coagulation, hemolytic anemia, thrombocytopenia, neutropenia, acute kidney injury, rhabdomyolysis, liver toxicity, cardiac ischemia, respiratory failure, hypoglycemia, blindness, and toxic epidermal necrolysis. One hundred-two (72%) reactions were caused by quinine pills; 28 (20%) by quinine-containing beverages; 12 (8%) by five other types of exposures. Excluding 41 patients who had only dermatologic reactions, 92 (91%) of 101 patients had required hospitalization for severe illness; 30 required renal replacement therapy; three died. Quinine, even with only minute exposure from common beverages, can cause severe adverse reactions involving multiple organ systems. In patients with acute, multi-system disorders of unknown origin, an adverse reaction to quinine should be considered. PMID- 26822546 TI - Diagnosis of airways obstruction should be based on symptoms and an FEV1/FVC ratio below the lower limit of normal. PMID- 26822545 TI - Cardiovascular alterations do exist in children with stage-2 chronic kidney disease. AB - BACKGROUND: Cardiovascular disease (CVD) is an important complication of chronic kidney disease (CKD) in children. However, it is not well known when and how cardiovascular alterations start. METHODS: This cross-sectional, controlled study consisted of 25 patients and 28 healthy controls. 24-h ambulatory blood pressure monitoring, aortic pulse wave velocity (aPWV), carotid intima-media thickness (cIMT) and carotid distensibility (distensibility coefficient and beta stiffness index), and echocardiography were assessed to evaluate CVD. Routine biochemical parameters, fibroblast growth factor-23 (FGF23) and high sensitive C- reactive protein were measured to determine cardiovascular risk factors. RESULTS: Hypertension was found in 12 patients (48 %). Patients had higher FGF23 levels and aPWV-standard deviation score (SDS) as compared to the controls (p = 0.003 and p = 0.002, respectively). Aortic PWV-SDS was predicted by increased daytime systolic blood pressure load (beta = 0.512, p = 0.009, R 2 = 0.262). Neither cIMT nor distensibility differed between the groups; however, older age and high level of FGF23 were independent predictors of beta stiffness index in patients (beta = 0.507, p = 0.005, R 2 = 0.461 and beta = 0.502, p = 0.005, R 2 = 0.461, respectively). As compared to controls, patients had worse left ventricular diastolic function [lower E/A ratio p = 0.006) and increased left atrial dimension (p < 0.001)]. CONCLUSIONS: Cardiovascular deteriorations appear in children with stage-2 CKD. Good control of BP and decreasing the level of FGF23 may be useful to slow down the progression of cardiovascular complications. PMID- 26822547 TI - Developing a multidisciplinary Young Women's Blood Disorders Program: a single centre approach with guidance for other centres. AB - INTRODUCTION: Bleeding from the reproductive tract in women is a natural event, generally occurring with menstruation and childbirth. Women with an underlying bleeding disorder may experience heavy menstrual bleeding (HMB) and thereby, unacceptable blood loss. Up to 20% of US women with abnormal uterine bleeding and a normal gynaecological exam may have an underlying bleeding disorder corresponding to almost 2-3 million American women. These females face many obstacles in achieving optimum medical care for their problems. A haematologist may not evaluate these women as they are treated symptomatically. Recognition of an underlying bleeding disorder is not straightforward and many come to attention after serious bleeding events. Although mortality from HMB is uncommon, the true burden of HMB is its impact on health-related quality of life. To address these issues, women with HMB require a comprehensive approach to their care. METHODS: These reasons compelled us to institute a multidisciplinary Young Women's Blood Disorders (YWBD) Program at our institution. RESULTS: Herein, we describe the process of developing this program involving paediatric haematology, adolescent medicine and paediatric/adolescent gynaecology, and the expertise of a laboratory coagulationist, a nutritionist and nursing professionals. We also describe our experience with patient selection, the role of each specialty in the program, our approach to testing, the coordination of care and overall management of this patient population. Lastly, we propose metrics that could be followed in justifying the support of such a program. CONCLUSIONS: There is a growing need to offer comprehensive care to women with HMB and blood disorders. The YWBD program at our institution appears to be successful in delivering optimal care to young women affected with HMB. PMID- 26822548 TI - Nonresonant chemical mechanism in surface-enhanced Raman scattering of pyridine on M@Au12 clusters. AB - By employing density functional theory (DFT), this study presents a detailed analysis of nonresonant surface-enhanced Raman scattering (SERS) of pyridine on M@Au12 (M = V(-), Nb(-), Ta(-), Cr, Mo, W, Mn(+), Tc(+), and Re(+))-the stable 13 atom neutral and charged gold buckyball clusters. Changing the core atom in M@Au12 enabled us to modulate the direct chemical interactions between pyridine and the metal cluster. The results of our calculations indicate that the ground state chemical enhancement does not increase as the binding interaction strengthens or the transfer charge increases between pyridine and the cluster. Instead, the magnitude of the chemical enhancement is governed, to a large extent, by the charged properties of the metal clusters. Pyridine on M@Au12 anion clusters exhibits strong chemical enhancement of a factor of about 10(2), but the equivalent increase for pyridine adsorbed on M@Au12 neutral and cation clusters is no more than 10. Polarizability and deformation density analyses clearly show that compared with the neutral and cation clusters, the anion clusters have more delocalized electrons and occupy higher energy levels in the pyridine-metal complex. Accordingly, they produce larger polarizability, leading to a stronger nonresonant enhancement effect. PMID- 26822549 TI - Value of Quantitative assessment of Myeloid Nuclear Differentiation Antigen expression and other flow cytometric parameters in the diagnosis of Myelodysplastic syndrome. AB - INTRODUCTION: The diagnosis of myelodysplastic syndrome (MDS) based on morphology is particularly difficult in low-grade MDS. Thus, the role of myeloid nuclear differentiation antigen (MNDA) and other flow cytometric (FCM) parameters in MDS was evaluated. METHODS: Bone marrow aspirates (BMA) collected from 52 patients with unexplained persistent cytopenias were divided into three groups: (i) proven MDS (n = 12) based on morphology and/or cytogenetics; (ii) suspected MDS (n = 6), noncontributory morphology, and cytogenetics; and (iii) non-MDS (n = 34). Sixteen control BMA were studied. Cases were analyzed for MNDA expression (on granulocytes, blasts, monocytes, and lymphocytes) and for seven quantitative parameters: CD34(+) myeloblasts % in nucleated cells, CD34(+) B-cell progenitor% in CD34(+) cells, lymphocyte/myeloblast CD45 MFI ratio, granulocyte/lymphocyte SSC peak channel ratio and the proportion of CD34(+) myeloblasts expressing CD15, CD11b, and CD56. A score of 1 was given to each parameter beyond the cutoff, and score >=3 was considered FCM positive. RESULTS: MNDA expression on granulocytes and blasts was significantly lower in proven MDS and suspected MDS vs. non-MDS. Quantitative FCM parameters successfully distinguished MDS and suspected MDS from non-MDS. CONCLUSION: MNDA expression is an independent marker for the evaluation of dyspoiesis and may be added to the standard panel for quantitative assessment by FCM. PMID- 26822550 TI - Role of cleansers in the management of acne: Results of an Italian survey in 786 patients. AB - BACKGROUND: Modern therapy of acne is based also on moisturizers, cleansers and sunscreens. However, a few studies have been published on cleansers, and never in Italy. OBJECTIVE: We decided to carry out an epidemiological study on the knowledge, beliefs and perceptions of acne patients regarding cleansers. METHODS: The survey has been carried out in Italy in 2013-2014. A group of patients with acne completed a questionnaire which included 10 questions. RESULTS: One hundred and eighteen dermatologists and 786 evaluable acne patients attended the survey. Approximately 70% of patients use a specific anti-acne cleanser. This cleanser is suggested in 57% of cases by a dermatologist. The patients buy this cleanser at the pharmacy (77% of cases). More than 62% of patients are satisfied about this cleanser. More than 66% of patients use the cleanser twice daily. The length of washing is less than one minute in 48% of patients. More than 66% of patients believe that the cleanser has a therapeutical role. CONCLUSION: The results of this survey cannot be compared with other studies because of the lack of similar studies about this topic. These results suggest that a sample of Italian acne patients consider cleansers as an important adjuvant treatment in acne. PMID- 26822551 TI - Interpreting infant emotional expressions: Parenthood has differential effects on men and women. AB - Interpreting and responding to an infant's emotional cues is a fundamental parenting skill. Responsivity to infant cues is frequently disrupted in depression, impacting negatively on child outcomes, which underscores its importance. It is widely assumed that women, and in particular mothers, show greater attunement to infants than do men. However, empirical evidence for sex and parental status effects, particularly in relation to perception of infant emotion, has been lacking. In this study, men and women with and without young infants were asked to rate valence in a range of infant facial expressions, on a scale of very positive to very negative. Results suggested complex interaction effects between parental status, sex, and the facial expression being rated. Mothers provided more positive ratings of the happy expressions and more extreme ratings of the intense emotion expressions than fathers, but non-mothers and non fathers did not. Low-level depressive symptoms were also found to correlate with more negative ratings of negative infant facial expressions across the entire sample. Overall, these results suggest that parental status might have differential effects on men and women's appraisal of infant cues. Differences between fathers' and mothers' perceptions of infant emotion might be of interest in understanding variance in interaction styles, such as proportion of time spent in play. PMID- 26822552 TI - Plasmin cleaves fibrinogen and the human complement proteins C3b and C5 in the presence of Leptospira interrogans proteins: A new role of LigA and LigB in invasion and complement immune evasion. AB - Plasminogen is a single-chain glycoprotein found in human plasma as the inactive precursor of plasmin. When converted to proteolytically active plasmin, plasmin(ogen) regulates both complement and coagulation cascades, thus representing an important target for pathogenic microorganisms. Leptospira interrogans binds plasminogen, which is converted to active plasmin. Leptospiral immunoglobulin-like (Lig) proteins are surface exposed molecules that interact with extracellular matrix components and complement regulators, including proteins of the FH family and C4BP. In this work, we demonstrate that these multifunctional molecules also bind plasminogen through both N- and C-terminal domains. These interactions are dependent on lysine residues and are affected by ionic strength. Competition assays suggest that plasminogen does not share binding sites with C4BP or FH on Lig proteins at physiological molar ratios. Plasminogen bound to Lig proteins is converted to proteolytic active plasmin in the presence of urokinase-type plasminogen activator (uPA). Lig-bound plasmin is able to cleave the physiological substrates fibrinogen and the complement proteins C3b and C5. Taken together, our data point to a new role of LigA and LigB in leptospiral invasion and complement immune evasion. Plasmin(ogen) acquisition by these versatile proteins may contribute to Leptospira infection, favoring bacterial survival and dissemination inside the host. PMID- 26822553 TI - Analyses of Long Non-Coding RNA and mRNA profiling using RNA sequencing during the pre-implantation phases in pig endometrium. AB - Establishment of implantation in pig is accompanied by a coordinated interaction between the maternal uterine endometrium and conceptus development. We investigated the expression profiles of endometrial tissue on Days 9, 12 and 15 of pregnancy and on Day 12 of non-pregnancy in Yorkshire, and performed a comprehensive analysis of long non-coding RNAs (lncRNAs) in endometrial tissue samples by using RNA sequencing. As a result, 2805 novel lncRNAs, 2,376 (301 lncRNA and 2075 mRNA) differentially expressed genes (DEGs) and 2149 novel transcripts were obtained by pairwise comparison. In agreement with previous reports, lncRNAs shared similar characteristics, such as shorter in length, lower in exon number, lower at expression level and less conserved than protein coding transcripts. Bioinformatics analysis showed that DEGs were involved in protein binding, cellular process, immune system process and enriched in focal adhesion, Jak-STAT, FoxO and MAPK signaling pathway. We also found that lncRNAs TCONS_01729386 and TCONS_01325501 may play a vital role in embryo pre implantation. Furthermore, the expression of FGF7, NMB, COL5A3, S100A8 and PPP1R3D genes were significantly up-regulated at the time of maternal recognition of pregnancy (Day 12 of pregnancy). Our results first identified the characterization and expression profile of lncRNAs in pig endometrium during pre implantation phases. PMID- 26822556 TI - New role for ceramide in the pheromone response. PMID- 26822555 TI - Is protection against florivory consistent with the optimal defense hypothesis? AB - BACKGROUND: Plant defense traits require resources and energy that plants may otherwise use for growth and reproduction. In order to most efficiently protect plant tissues from herbivory, one widely accepted assumption of the optimal defense hypothesis states that plants protect tissues most relevant to fitness. Reproductive organs directly determining plant fitness, including flowers and immature fruit, as well as young, productive leaf tissue thus should be particularly well-defended. To test this hypothesis, we quantified the cyanogenic potential (HCNp)-a direct, chemical defense-systemically expressed in vegetative and reproductive organs in lima bean (Phaseolus lunatus), and we tested susceptibility of these organs in bioassays with a generalist insect herbivore, the Large Yellow Underwing (Noctuidae: Noctua pronuba). To determine the actual impact of either florivory (herbivory on flowers) or folivory on seed production as a measure of maternal fitness, we removed varying percentages of total flowers or young leaf tissue and quantified developing fruit, seeds, and seed viability. RESULTS: We found extremely low HCNp in flowers (8.66 +/- 2.19 MUmol CN(-) g(-1) FW in young, white flowers, 6.23 +/- 1.25 MUmol CN(-) g(-1) FW in mature, yellow flowers) and in pods (ranging from 32.05 +/- 7.08 to 0.09 +/- 0.08 MUmol CN(-) g( 1) FW in young to mature pods, respectively) whereas young leaves showed high levels of defense (67.35 +/- 3.15 MUmol CN(-) g(-1) FW). Correspondingly, herbivores consumed more flowers than any other tissue, which, when taken alone, appears to contradict the optimal defense hypothesis. However, experimentally removing flowers did not significantly impact fitness, while leaf tissue removal significantly reduced production of viable seeds. CONCLUSIONS: Even though flowers were the least defended and most consumed, our results support the optimal defense hypothesis due to i) the lack of flower removal effects on fitness and ii) the high defense investment in young leaves, which have high consequences for fitness. These data highlight the importance of considering plant defense interactions from multiple angles; interpreting where empirical data fit within any plant defense hypothesis requires understanding the fitness consequences associated with the observed defense pattern. PMID- 26822554 TI - Eukaryotic genome instability in light of asymmetric DNA replication. AB - The eukaryotic nuclear genome is replicated asymmetrically, with the leading strand replicated continuously and the lagging strand replicated as discontinuous Okazaki fragments that are subsequently joined. Both strands are replicated with high fidelity, but the processes used to achieve high fidelity are likely to differ. Here we review recent studies of similarities and differences in the fidelity with which the three major eukaryotic replicases, DNA polymerases alpha, delta, and E, replicate the leading and lagging strands with high nucleotide selectivity and efficient proofreading. We then relate the asymmetric fidelity at the replication fork to the efficiency of DNA mismatch repair, ribonucleotide excision repair and topoisomerase 1 activity. PMID- 26822558 TI - Improving the Quality of End-of-Life Care. PMID- 26822557 TI - Changes in the strength of peer influence and cultural factors on substance use initiation between late adolescence and emerging adulthood in a Hispanic sample. AB - We examine whether peer substance use and cultural factors differentially influence the initiation of tobacco, alcohol, and marijuana use in adolescence and emerging adulthood (EA) among a community-based sample of Hispanics. Participants provided data in 11th grade (M = 16.8 years old, SD = 0.54) and emerging adulthood (M = 20.3 years old, SD = 0.6). Peer tobacco use had a stronger association with initiation of tobacco use in emerging adulthood (OR = 1.46, 95% CI = 1.13, 1.89) than in adolescence (OR = 1.20, 95% CI = 1.03, 1.40), but this pattern was not observed with initiation of alcohol or marijuana use. Cultural orientation is associated with initiation of tobacco use during EA but not with initiation of alcohol or marijuana use. PMID- 26822559 TI - The Burden of Overmedication: What Are the Real Issues? PMID- 26822560 TI - Algorithms Promoting Antimicrobial Stewardship in Long-Term Care. PMID- 26822561 TI - Brief Report: Healing Touch Consults at a Tertiary Care Children's Hospital. AB - BACKGROUND AND OBJECTIVES: Components of complementary and alternative medicine are increasingly being implemented at academic medical centers. These approaches include therapeutic touch or healing touch (HT), an energy-based therapy using light touch on or near the body. Limited data exist regarding complementary and alternative medicine use at children's hospitals. The aim of this study was to evaluate patterns and clinical characteristics of HT consultations among children hospitalized at Nemours/A.I. duPont Hospital for Children. METHODS: We conducted a retrospective chart review of all patients hospitalized from January 2012 through December 2013, comparing patients who received HT consultations with those who did not. RESULTS: There were 25,396 admissions during the study period; 882 (4%) of these, representing 593 individual patients, received an HT consultation. As compared with those without an HT consultation, patients receiving HT were older (median 12 years vs 5 years, P<.001), female (58% vs 46%, P<.001), and more likely to be admitted to the hematology/oncology or blood/bone marrow transplant units (P<.001). Patients with HT consultations had longer hospitalizations (median 121 hours vs 38 hours, P<.001) and more medical problems (median 12 vs 4, P<.001). Six attending physicians were responsible for placing the majority of HT consultations. Of the 593 patients receiving an HT consultation, 21% received >=2 consultations during the study period. CONCLUSIONS: Certain patients, such as those with longer hospitalizations and more medical problems, were more likely to receive HT consultations. Many patients received multiple consultations, suggesting that HT may be an important aspect of ongoing care for hospitalized children. PMID- 26822562 TI - alpha-trideuteromethyl[15N]glutamine: A long-lived hyperpolarized perfusion marker. AB - PURPOSE: We characterized the performance of a novel hyperpolarized perfusion marker, alpha-trideuteromethyl[15N]glutamine, for direct comparison with a 13C based hyperpolarized perfusion marker, [13C, 15N2]urea. METHODS: A hardware platform and pulse sequence for in vivo 15N experiments were established. Hyperpolarized solutions of alpha-trideuteromethyl[15N]glutamine and [13C, 15N2]urea were injected into healthy male Lewis rats. Kidney slice images were acquired using a single-shot spiral readout. Both compounds were compared to determine in vivo signal lifetime and tracer distribution. Mass spectrometry was performed to evaluate excretion of the compound. RESULTS: Compared with 13C labeled urea, a significantly increased signal lifetime was observed. While the urea signal was gone after 90 s, decay of the glutamine compound was sufficiently slow to obtain a quantifiable signal, even after 5 min. The glutamine derivative showed strong localization in the kidneys with little background signal. Effective T1 of alpha-trideuteromethyl[15N]glutamine was approximately eight-fold higher than that of urea. Mass spectrometry results confirmed rapid excretion within the time scale of the measurement. CONCLUSION: Hyperpolarized alpha trideuteromethyl[15N]glutamine is a highly promising candidate for renal studies because of its long signal lifetime, strong localization and rapid excretion. Magn Reson Med 76:1900-1904, 2016. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26822563 TI - A one-dimensional quantum walk with multiple-rotation on the coin. AB - We introduce and analyze a one-dimensional quantum walk with two time-independent rotations on the coin. We study the influence on the property of quantum walk due to the second rotation on the coin. Based on the asymptotic solution in the long time limit, a ballistic behaviour of this walk is observed. This quantum walk retains the quadratic growth of the variance if the combined operator of the coin rotations is unitary. That confirms no localization exhibits in this walk. This result can be extended to the walk with multiple time-independent rotations on the coin. PMID- 26822564 TI - Bright Solid-State Emission of Disilane-Bridged Donor-Acceptor-Donor and Acceptor Donor-Acceptor Chromophores. AB - The development of disilane-bridged donor-acceptor-donor (D-Si-Si-A-Si-Si-D) and acceptor-donor-acceptor (A-Si-Si-D-Si-Si-A) compounds is described. Both types of compound showed strong emission (lambdaem =ca. 500 and ca. 400 nm, respectively) in the solid state with high quantum yields (Phi: up to 0.85). Compound 4 exhibited aggregation-induced emission enhancement in solution. X-ray diffraction revealed that the crystal structures of 2, 4, and 12 had no intermolecular pi-pi interactions to suppress the nonradiative transition in the solid state. PMID- 26822565 TI - Recombinant IGF-I: Past, present and future. AB - Normal linear growth in humans requires GH and IGF-I. Diminished GH action resulting in reduced availability of IGF-I and IGF-binding proteins is the hallmarks of GH Insensitivity Syndromes (GHIS). The deficiencies are the perceived mechanisms for the growth failure of affected patients and the therapeutic targets for the restoration of normal growth. Early treatment attempts with pituitary-derived GH had limited effects in GHIS patients. Recombinant human insulin-like growth factor-I (rhIGF-I) treatment initially provides accelerated growth to GHIS children and provides substantial benefit. But, in general, catch up growth is less substantial with rhIGF-I treatment of GHIS than with rhGH treatment of GH Deficiency. Few classic GHIS patients have reached heights in the normal range (height SD score between -2.0 SD and +2.0 SD) with rhIGF-I monotherapy. A potential explanation is that while rhIGF-I treatment increases circulating concentrations of IGF-1 and IGFBP-3, such treatment reduces endogenous GH levels by negative feedback inhibition of pituitary GH release. In as much as both GH and IGF-I are required for good catch up growth, the loss of any residual GH signaling during IGF-I monotherapy in GHIS patients may attenuate possible catch up growth. Consistent with this explanation is the finding that, as predicted by the preclinical studies by Ross Clark, combination of rhGH & rhIGF-1 provides better growth responses than rhIGF-1 monotherapy in prepubertal children with short stature and low IGF-I levels despite normal stimulated GH responses. In the future, rhGH and rhIGF-I combination therapy can potentially improve growth outcomes over that seen with rhIGF-I monotherapy in all GHIS patients except in those with a total lack of functional GH signaling. Future alternative treatments for GHIS subjects may also include the use of post-growth hormone receptor signaling agonists which restore both GH signaling and IGF-I exposures or the addition of long-acting rhGH species to rhIGF-I. Additional etiologic factors for the growth failure in GHIS should be considered if the growth deficits of GHIS do not resolve with treatment. PMID- 26822566 TI - Symmetric 4,4'-(piperidin-4-ylidenemethylene)bisphenol derivatives as novel tunable estrogen receptor (ER) modulators. AB - We designed and synthesized 4,4'-(piperidin-4-ylidenemethylene)bisphenol derivatives as novel tunable estrogen receptor (ER) modulators. The introduction of hydrophobic substituents on the nitrogen atom of the piperidine ring enhanced ERalpha binding affinity. In addition, the introduction of four methyl groups adjacent to the piperidine ring nitrogen atom remarkably enhanced ERalpha binding affinity. N-Acetyl-2,2,6,6-tetramethylpiperidine derivative 3b showed high ERalpha binding affinity, high MCF-7 cell proliferation inducing activity, and high metabolic stability in rat liver S9 fractions. PMID- 26822567 TI - Overcoming multidrug resistance by targeting mitochondria with NO-donating doxorubicins. AB - A library of nitric oxide-donor doxorubicins (NO-DOXOs) was synthesized by linking appropriate NO-donor moieties at C-14 position through an ester bridge. Their hydrolytic stability was evaluated. The intracellular accumulation and cytotoxicity of these novel NO-DOXOs were studied in DOXO-sensitive (HT29) and DOXO-resistant (HT29/dx) tumor-cells. Hydrolytically-stable compounds accumulated in HT29 and HT29/dx cells, thanks to the nitration of plasma-membrane efflux transporters. Surprisingly, no close correlation was found between intracellular accumulation and cytotoxicity. Only compounds with high mitochondria retention (due to nitration of mitochondrial efflux transporter) exert high cytotoxicity, through the activation of a mitochondrial-dependent apoptosis. PMID- 26822568 TI - Discovery of potent anti-tuberculosis agents targeting leucyl-tRNA synthetase. AB - Tuberculosis is a serious infectious disease caused by human pathogen bacteria Mycobacterium tuberculosis. Bacterial drug resistance is a very significant medical problem nowadays and development of novel antibiotics with different mechanisms of action is an important goal of modern medical science. Leucyl-tRNA synthetase (LeuRS) has been recently clinically validated as antimicrobial target. Here we report the discovery of small-molecule inhibitors of M. tuberculosis LeuRS. Using receptor-based virtual screening we have identified six inhibitors of M. tuberculosis LeuRS from two different chemical classes. The most active compound 4-{[4-(4-Bromo-phenyl)-thiazol-2-yl]hydrazonomethyl}-2-methoxy-6 nitro-phenol (1) inhibits LeuRS with IC50 of 6MUM. A series of derivatives has been synthesized and evaluated in vitro toward M. tuberculosis LeuRS. It was revealed that the most active compound 2,6-Dibromo-4-{[4-(4-nitro-phenyl)-thiazol 2-yl]-hydrazonomethyl}-phenol inhibits LeuRS with IC50 of 2.27MUM. All active compounds were tested for antimicrobial effect against M. tuberculosis H37Rv. The compound 1 seems to have the best cell permeability and inhibits growth of pathogenic bacteria with IC50=10.01MUM and IC90=13.53MUM. PMID- 26822570 TI - Pancreatic cancer: Spotlight on B cells. PMID- 26822569 TI - Practical and Reliable Synthesis of 1,2-Dideoxy-d-ribofuranose and its Application in RNAi Studies. AB - We developed a practical and reliable method for synthesizing an abasic deoxyribonucleoside, 1,2-dideoxy-d-ribofuranose (dR(H)) via elimination of nucleobase from thymidine. To synthesize oligonucleotides bearing dR(H) by the standard phosphoramidite solid-phase method, dR(H) was converted to the corresponding phosphoramidite derivative and linked to a solid support (controlled pore glass resin). Chemically modified small interfering RNAs (siRNAs) possessing dR(H) at their 3'-overhang regions were synthesized. Introducing dR(H) to the 3'-end of the antisense strand of siRNA reduced its knockdown effect. PMID- 26822575 TI - A panoply of errors: polymerase proofreading domain mutations in cancer. AB - Although it has long been recognized that the exonucleolytic proofreading activity intrinsic to the replicative DNA polymerases Pol delta and Pol epsilon is essential for faithful replication of DNA, evidence that defective DNA polymerase proofreading contributes to human malignancy has been limited. However, recent studies have shown that germline mutations in the proofreading domains of Pol delta and Pol epsilon predispose to cancer, and that somatic Pol epsilon proofreading domain mutations occur in multiple sporadic tumours, where they underlie a phenotype of 'ultramutation' and favourable prognosis. In this Review, we summarize the current understanding of the mechanisms and consequences of polymerase proofreading domain mutations in human malignancies, and highlight the potential utility of these variants as novel cancer biomarkers and therapeutic targets. PMID- 26822576 TI - The kinome 'at large' in cancer. AB - Over the past decade, rapid advances in genomics, proteomics and functional genomics technologies that enable in-depth interrogation of cancer genomes and proteomes and high-throughput analysis of gene function have enabled characterization of the kinome 'at large' in human cancers, providing crucial insights into how members of the protein kinase superfamily are dysregulated in malignancy, the context-dependent functional role of specific kinases in cancer and how kinome remodelling modulates sensitivity to anticancer drugs. The power of these complementary approaches, and the insights gained from them, form the basis of this Analysis article. PMID- 26822578 TI - Acquired resistance to immunotherapy and future challenges. AB - Advances in immunotherapy have resulted in remarkable clinical responses in some patients. However, one of the biggest challenges in cancer therapeutics is the development of resistant disease and disease progression on or after therapy. Given that many patients have now received various types of immunotherapy, we asked three scientists to give their views on the current evidence for whether acquired resistance to immunotherapy exists in patients and the future challenges posed by immunotherapy. PMID- 26822580 TI - Indications for and outcome of open AAA repair in the endovascular era. AB - The benefits, safety and efficacy of endovascular aortic aneurysm repair (EVAR) is well documented and intensively reported in multiple randomized trials and meta-analysis. Therefore, EVAR became the first choice of abdominal aortic aneurysms (AAA) treatment in almost 70-100% of patients. Consecutively, open repair (OR) is performed less frequently in morphologically preselected patients. Anatomical condition remains the most important factor for indication for OR. Especially unfavorable intrarenal landing zone based on difficult neck anatomy like very short neck or excessive neck angulation is still the most predictive factor. Furthermore, patients presenting additional iliac aneurysms, aortoiliac occlusive disease or variations of renal arteries are recommended for OR. Randomized trials like EVAR 1, DREAM and OVER from the year 2004/2005 and 2009 showed lower 30-day mortality rates in EVAR compared to OR. However, the late mortality rates after two years became equal in both treatment options. Furthermore, reinterventions after EVAR occur more frequently than after OR. Analysis from our own data showed a higher 30-day mortality in the patients who underwent OR in the endovascular era (15% vs. 2.5%), however the number of emergency open AAA repair because of ruptured aneurysms was much higher in the endovascular era (32.5% vs. 5%). In conclusion, treatment of AAA has changed in the past decade. Nevertheless OR of AAA still remains as a safe and durable method in experienced surgeons, even in the endovascular era. High volume centres are needed to offer the best patients' treatment providing the best postoperative outcome. Therefore OR must remain a part of fellowship training in the future. To decide the best treatment option many facts like patients' fitness and preference or finally the anatomic suitability for endovascular repair have to be considered. PMID- 26822579 TI - Vorvida: study protocol of a randomized controlled trial testing the effectiveness of Internet-based self-help program for the reduction of alcohol consumption for adults. AB - BACKGROUND: Problem drinking is an important global health concern, causing premature mortality and morbidity. Only few problem drinkers seek professional care, unfortunately, because of multiple barriers such as insufficient change motivation, fear of stigmatization or limited access to care. The aim of this study will be to examine the effectiveness of a novel Internet intervention termed Vorvida, which was developed based on established cognitive-behavioral therapy techniques with the aim of reducing problematic alcohol consumption. METHODS/DESIGN: A two-arm randomized control trial (RCT) will be conducted to determine whether using Vorvida results in greater reductions in self-reported problem drinking, compared with a care-as-usual/waitlist (CAU/WL) control group. There will be a baseline assessment (t0) and follow-up assessments after three (t1) and six months (t2). Inclusion criteria will be: minimum age of 18, an average consumption of alcohol >24/12 g (men/women) per day and an AUDIT-C score >= 3, as well as informed consent. Participants will be randomly assigned to the intervention or control condition at a ratio of 1:1. Recruitment, informed consent, randomization and assessment will be Internet-based. Primary outcome will be change in self-reported alcohol consumption between t0 and t1. Secondary outcomes will be self-reported drinking behavior, expectancies of effects of alcohol use, abstinence and relapse tendencies, self-efficacy and motivation to change. DISCUSSION: This study is expected to establish the extent to which a novel Internet intervention could contribute to reducing problem drinking among adults with mild to severe alcohol use disorders who may or may not seek or access a traditional treatments. Potentially, this program could be an effective and efficient tool to help reduce problem drinking on a population level because a great number of users can be reached simultaneously without adding burden to treating clinicians. TRIAL REGISTRATION: German Clinical Trial Registration (DRKS): DRKS00006104. Registered 14 April 2014. PMID- 26822581 TI - The progression of aortic aneurysms. AB - Aortic aneurysm is a progressive disease that can involve any territory of the aorta. This has ramifications on endovascular repair, because progressive dilation of sealing zones can compromise the integrity of the repair and lead to long term failure. This article describes the evidence behind and some of the predictors of progressive disease of the aorta. Knowledge of predictors of progressive disease may help prevent it from causing failure in the longterm by helping to tailor surveillance routines or have influence on initial graft design. PMID- 26822577 TI - Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies. AB - The 'hallmarks of cancer' are generally accepted as a set of genetic and epigenetic alterations that a normal cell must accrue to transform into a fully malignant cancer. It follows that therapies designed to counter these alterations might be effective as anti-cancer strategies. Over the past 30 years, research on the BCL-2-regulated apoptotic pathway has led to the development of small molecule compounds, known as 'BH3-mimetics', that bind to pro-survival BCL-2 proteins to directly activate apoptosis of malignant cells. This Timeline article focuses on the discovery and study of BCL-2, the wider BCL-2 protein family and, specifically, its roles in cancer development and therapy. PMID- 26822583 TI - Access to and affordability of healthcare for TB patients in China: issues and challenges. AB - This paper introduces the background, aim and objectives of the project entitled "China-the Gates Foundation Collaboration on TB Control in China" that has been underway for many years. It also summarizes the key findings of the nine papers included in this special issue, which used data from the baseline survey of Phase II of the project. Data were collected from the survey of TB and MDR-TB patients, from designated hospitals, health insurance agencies and the routine health information systems, as well as key informant interviews and focus group discussions with relevant key stakeholders. Key issues discussed in this series of papers include the uses of TB services and anti-TB medicines and their determining factors related to socio-economic and health systems development; expenditures on TB care and the financial burden incurred on TB patients; and the impact of health insurance schemes implemented in China on financial protection. PMID- 26822582 TI - Low-intensity resistance training with blood flow restriction improves vascular endothelial function and peripheral blood circulation in healthy elderly people. AB - PURPOSE: The present study aimed to investigate the effects of low-intensity resistance training with blood flow restriction (BFR resistance training) on vascular endothelial function and peripheral blood circulation. METHODS: Forty healthy elderly volunteers aged 71 +/- 4 years were divided into two training groups. Twenty subjects performed BFR resistance training (BFR group), and the remaining 20 performed ordinary resistance training without BFR. Resistance training was performed at 20 % of each estimated one-repetition maximum for 4 weeks. We measured lactate (Lac), norepinephrine (NE), vascular endothelial growth factor (VEGF) and growth hormone (GH) before and after the initial resistance training. The reactive hyperemia index (RHI), von Willebrand factor (vWF) and transcutaneous oxygen pressure in the foot (Foot-tcPO2) were assessed before and after the 4-week resistance training period. RESULTS: Lac, NE, VEGF and GH increased significantly from 8.2 +/- 3.6 mg/dL, 619.5 +/- 243.7 pg/mL, 43.3 +/- 15.9 pg/mL and 0.9 +/- 0.7 ng/mL to 49.2 +/- 16.1 mg/dL, 960.2 +/- 373.7 pg/mL, 61.6 +/- 19.5 pg/mL and 3.1 +/- 1.3 ng/mL, respectively, in the BFR group (each P < 0.01). RHI and Foot-tcPO2 increased significantly from 1.8 +/- 0.2 and 62.4 +/- 5.3 mmHg to 2.1 +/- 0.3 and 68.9 +/- 5.8 mmHg, respectively, in the BFR group (each P < 0.01). VWF decreased significantly from 175.7 +/- 20.3 to 156.3 +/- 38.1 % in the BFR group (P < 0.05). CONCLUSIONS: BFR resistance training improved vascular endothelial function and peripheral blood circulation in healthy elderly people. PMID- 26822584 TI - Effects of Plants on Osteogenic Differentiation and Mineralization of Periodontal Ligament Cells: A Systematic Review. AB - This systematic review aimed to evaluate the effects of plants on osteogenic differentiation and mineralization of human periodontal ligament cells. The included studies were selected using five different electronic databases. The reference list of the included studies was crosschecked, and a partial gray literature search was undertaken using Google Scholar and ProQuest. The methodology of the selected studies was evaluated using GRADE. After a two-step selection process, eight studies were identified. Six different types of plants were reported in the selected studies, which were Morinda citrifolia, Aloe vera, Fructus cnidii, Zanthoxylum schinifolium, Centella asiatica, and Epimedium species. They included five types of isolated plant components: acemannan, osthole, hesperetin, asiaticoside, and icariin. In addition, some active substances of these components were identified as polysaccharides, coumarins, flavonoids, and triterpenes. The studies demonstrated the potential effects of plants on osteogenic differentiation, cell proliferation, mineral deposition, and gene and protein expression. Four studies showed that periodontal ligament cells induce mineral deposition after plant treatment. Although there are few studies on the subject, current evidence suggests that plants are potentially useful for the treatment of periodontal diseases. However, further investigations are required to confirm the promising effect of these plants in regenerative treatments. PMID- 26822585 TI - Campus Sexual Violence Resources and Emotional Health of College Women Who Have Experienced Sexual Assault. AB - Institutional characteristics may help mitigate trauma associated with sexual assault. This study examines associations between resources on college campuses for sexual violence prevention and the emotional well-being of female students who have experienced sexual assault. There were 495 female college students who have experienced sexual assault who provided survey data in 2010-2011. Sexual violence resource data from 28 college campuses were combined with student survey data in multilevel analysis. Dependent variables include diagnosis with anxiety, depression, panic attacks, and PTSD, and models adjust for covariates and clustering of students within colleges. Participants attending colleges with more sexual violence resources had lower rates of mental health conditions than those attending colleges with fewer resources. Colleges are encouraged to expand their array of sexual violence resources to create a supportive environment for victims of sexual assault and to connect affected students with appropriate services. PMID- 26822587 TI - Thickness- and Particle-Size-Dependent Electrochemical Reduction of Carbon Dioxide on Thin-Layer Porous Silver Electrodes. AB - The electrochemical reduction of CO2 can not only convert it back into fuels, but is also an efficient manner to store forms of renewable energy. Catalysis with silver is a possible technology for CO2 reduction. We report that in the case of monolithic porous silver, the film thickness and primary particle size of the silver particles, which can be controlled by electrochemical growth/reduction of AgCl film on silver substrate, have a strong influence on the electrocatalytic activity towards CO2 reduction. A 6 MUm thick silver film with particle sizes of 30-50 nm delivers a CO formation current of 10.5 mA cm(-2) and a mass activity of 4.38 A gAg (-1) at an overpotential of 0.39 V, comparable to levels achieved with state-of-the-art gold catalysts. PMID- 26822586 TI - Blocking heme oxygenase-1 by zinc protoporphyrin reduces tumor hypoxia-mediated VEGF release and inhibits tumor angiogenesis as a potential therapeutic agent against colorectal cancer. AB - BACKGROUND: Hypoxia in tumor niche is one of important factors to start regeneration of blood vessels, leading to increase survival, proliferation, and invasion in cancer cells. Under hypoxia microenvironment, furthermore, steadily increased hypoxia-inducible factor -1alpha (HIF-1alpha) is observed, and can increase vascular endothelial growth factor (VEGF) expression and promote angiogenesis. Zinc protoporphyrin (ZnPP), a heme oxygenase-1 (HO-1) inhibitor, is potential to inhibit tumor proliferation and progression. However, the mechanism of ZnPP in inhibition of tumor is not completely clear. We hypothesize that ZnPP may modulate HIF-1alpha through inhibiting HO-1, and then inhibit angiogenesis and tumor progression. This study aimed to dissect the mechanism of ZnPP in tumor suppression. RESULTS: We observed the amount of VEGF was increased in the sera of the colorectal cancer (CRC) patients (n = 34, p < 0.05). Furthermore, increased VEGF expression was also measured in colorectal cancer cells, HCT-15, culturing under mimicking hypoxic condition. It suggested that hypoxia induced VEGF production from cancer cells. VEGF production was significantly reduced from HCT 15 cells after exposure to HIF-1alpha inhibitor KC7F2, suggesting that HIF-1alpha regulated VEGF production. Moreover, we observed that the HO-1 inhibitor ZnPP inhibited the expressions of HIF-1alpha and VEGF coupled with cell proliferations of HCT-15 cells, suggesting that ZnPP blocked HIF-1alpha expression, and then inhibited the consequent VEGF production. In the xenograft model, we also observed that the animals exposed to ZnPP displayed much smaller tumor nodules and less degree of angiogenesis with decreased expression of the angiogenesis marker, alphavbeta3 integrin, compared to that in normal control. CONCLUSIONS: This study demonstrated that VEGF level in serum was elevated in the patients with CRC. The HO-1 inhibitor, ZnPP, possessed the properties of anti-tumor agent by decreasing HIF-1alpha levels, blocking VEGF production, impairing tumor angiogenesis, and inhibiting tumor growth. PMID- 26822588 TI - Novel Method for Real Time Co-Registration of IVUS and Coronary Angiography. AB - OBJECTIVES: We present our experience with a novel method for real time co registration of intravascular ultrasound (IVUS) and coronary angiography. BACKGROUND: A major limitation of the current practice of concomitant use of coronary angiography and IVUS is that the locations of the acquired IVUS images are not correlated with their exact locations on the vessel roadmap obtained by coronary angiography. METHODS: Phantoms simulating the coronary tree were used to test the accuracy and potential of co-registration. Subsequently we examined patients who underwent IVUS during cardiac catheterization. Analysis and feasibility were performed in 42 arteries of 36 patients. RESULTS: The statistical validation in phantoms resulted in a co-registration accuracy of 1.12 mm. The length measurement on an angiogram resulted in an accuracy of 0.38 mm. Co registration in patients was successful in all cases and four categories were assisted by 1(bad) to 5 (good) grading. Accuracy (the co-registration precision in pointing at the exact corresponding location): 4.8+/-0.41; Ease of use and workflow: 4.74+/-0.44; Stent landing zone detection and evaluation: 4.58+/-0.5; Stent landing zone length and diameter measurement: 4.94+/-0.23. The co registration error was estimated as no more than 1 mm. CONCLUSION: In this pilot study, we found that the novel IVUS and coronary angiography co-registration method is accurate, easy to use, fast and user-friendly. This method precludes the need to use motorized automated pull back device. PMID- 26822590 TI - Up-and-down shift in residence depth of slickheads (Alepocephalidae) revealed by otolith stable oxygen isotopic composition. AB - Otolith delta(18)O profiles for four slickhead species (Alepocephalidae) suggested that Alepocephalus umbriceps, Talismania okinawensis and Rouleina watasei migrated hundreds of metres to shallower depths during the juvenile to young stages before returning to their original depth or even deeper waters. Xenodermichthys nodulosus gradually shifted residence depth from shallow to deeper water during their life. These migratory patterns indicated that the slickheads examined had allopatric residence depths at different life stages, which might enhance the pelagic survival and growth rates of the juvenile and young fishes. PMID- 26822589 TI - Surface-Enhanced Raman Spectroscopy as a Probe of the Surface Chemistry of Nanostructured Materials. AB - Surface-enhanced Raman spectroscopy (SERS) is now widely used as a rapid and inexpensive tool for chemical/biochemical analysis. The method can give enormous increases in the intensities of the Raman signals of low-concentration molecular targets if they are adsorbed on suitable enhancing substrates, which are typically composed of nanostructured Ag or Au. However, the features of SERS that allow it to be used as a chemical sensor also mean that it can be used as a powerful probe of the surface chemistry of any nanostructured material that can provide SERS enhancement. This is important because it is the surface chemistry that controls how these materials interact with their local environment and, in real applications, this interaction can be more important than more commonly measured properties such as morphology or plasmonic absorption. Here, the opportunity that this approach to SERS provides is illustrated with examples where the surface chemistry is both characterized and controlled in order to create functional nanomaterials. PMID- 26822591 TI - Performance and user acceptance of the Bhutan febrile and malaria information system: report from a pilot study. AB - BACKGROUND: Over the last decade, Bhutan has made substantial progress in controlling malaria. The country is now in an elimination phase, aiming to achieve no locally transmitted malaria by 2018. However, challenges remain and innovative control strategies are needed to overcome these. The evaluation and user acceptance of a robust surveillance tool applicable for informing malaria elimination activities is reported here. METHODS: The Bhutan Febrile and Malaria Information System (BFMIS) is a combination of web-based and mobile technology that captures malariometric surveillance data and generates real time reports. The system was rolled out at six sites and data uploaded regularly for analysis. Data completeness, accuracy and data turnaround time were accessed by comparison to traditional paper based surveillance records. User acceptance and willingness for further roll out was assessed using qualitative and quantitative data. RESULTS: Data completeness was nearly 10 % higher using the electronic system than the paper logs, and accuracy and validity of both approaches was comparable (up to 0.05 % in valid data and up to 3.06 % inaccurate data). Data turnaround time was faster using the BFMIS. General user satisfaction with the BFMIS was high, with high willingness of health facilities to adopt the system. Qualitative interviews revealed several areas for improvement before scale up. CONCLUSIONS: The BFMIS had numerous advantages over the paper-based system and based on the findings of the survey the Vector-Borne Disease Control Programme has taken the decision to incorporate the BMFIS and expand its use throughout all areas at risk for malaria as a key surveillance tool. PMID- 26822592 TI - A randomized controlled trial on the psychophysiological effects of physical exercise and Tai-chi in patients with chronic schizophrenia. AB - The chronic and prevalent natures of schizophrenia result in long-term institutionalization for the patients. Conventional treatment of anti-psychotic medication on management of psychotic symptoms often brings on severe side effects and reduces patients' well-being. Tai-chi is a mind-body exercise that underscores motor coordination and relaxation. This 3-arm randomized controlled trial investigated the psychophysiological benefits of Tai-chi on 153 chronic schizophrenia patients, who were recruited from a mental health rehab complex and randomized into Tai-chi, exercise, or waitlist control groups. Both intervention groups received 12weeks of specific intervention plus standard medication received by the controls. All participants completed psychiatric interviews, self report questionnaires, performance tasks, and salivary cortisol measures at baseline, 3-month, and 6-month follow-up on psychotic symptoms, motor coordination, memory, daily living function, and stress. Multigroup latent growth modeling was used to evaluate the intervention effects on the outcomes. Compared to controls, the Tai-chi group showed significant decreases in motor deficits and increases in backward digit span and mean cortisol, while the exercise group displayed significant decreases in motor deficits, negative and depression symptoms and increases in forward digit span, daily living function, and mean cortisol. The two interventions did not show significantly different therapeutic effects, except for fewer symptom manifestations in the exercise group. These results suggest psychophysiological benefits for Tai-chi on chronic schizophrenia patients in terms of motor coordination and memory. Though both Tai-chi and exercise groups tended to manifest fewer symptoms than the control group, the exercise group showed better symptoms management than the Tai-chi group. PMID- 26822593 TI - Mitochondrial genome variations and functional characterization in Han Chinese families with schizophrenia. AB - The relationship between mitochondrial DNA (mtDNA) variants and schizophrenia has been strongly debated. To test whether mtDNA variants are involved in schizophrenia in Han Chinese patients, we sequenced the entire mitochondrial genomes of probands from 11 families with a family history and maternal inheritance pattern of schizophrenia. Besides the haplogroup-specific variants, we found 11 nonsynonymous private variants, one rRNA variant, and one tRNA variant in 5 of 11 probands. Among the nonsynonymous private variants, mutations m.15395 A>G and m.8536 A>G were predicted to be deleterious after web-based searches and in silico program affiliated analysis. Functional characterization further supported the potential pathogenicity of the two variants m.15395 A>G and m.8536 A>G to cause mitochondrial dysfunction at the cellular level. Our results showed that mtDNA variants were actively involved in schizophrenia in some families with maternal inheritance of this disease. PMID- 26822594 TI - Complexities of Estimating Evolutionary Rates in Viruses. PMID- 26822595 TI - Reply to "Complexities of Estimating Evolutionary Rates in Viruses". PMID- 26822596 TI - Correction for Chen et al., Divergent MicroRNA Targetomes of Closely Related Circulating Strains of a Polyomavirus. PMID- 26822597 TI - Correction for Vigdorovich et al., Expression and Characterization of a Soluble, Active Form of the Jaagsiekte Sheep Retrovirus Receptor, Hyal2. PMID- 26822599 TI - Chikungunya: out of the tropical forests and heading our way .... PMID- 26822600 TI - Integrated epidemiology for vector-borne zoonoses. AB - The development and application of interventions for the control of vector-borne zoonoses requires broad understanding of epidemiological linkages between vector, animal infection and human infection. However, there are significant gaps in our understanding of these linkages and a lack of appropriate data poses a considerable barrier to addressing this issue. A move towards strengthened surveillance of vectors and disease in both animal and human hosts, in combination with linked human-animal surveys, could form the backbone for epidemiological integration, enabling explicit assessment of the animal-human (and vector) interface, and subsequent implications for spill-over to human populations. Currently available data on the spatial distribution of human African trypanosomiasis allow an illustrative example. PMID- 26822601 TI - Prospects, drawbacks and future needs of xenomonitoring for the endpoint evaluation of lymphatic filariasis elimination programs in Africa. AB - Lymphatic filariasis (LF) is a debilitating disease caused by Wuchereria bancrofti, Brugia malayi and B. timori parasitic worms and transmitted by Culex, Anopheles, Aedes and Mansonia mosquitoes. Mass drug administration (MDA) to reduce the infection levels in the human population is the key component of LF elimination programs. However, the potential of the use of vector control is gaining recognition as a tool that can complement MDA. The method of monitoring the parasites in mosquito vectors is known as xenomonitoring. Monitoring of vectors for filarial larvae is an important assessment tool for LF elimination programs. Xenomonitoring has the advantage of giving a real-time estimate of disease, because the pre-patent period may take months after infection in humans. It is a non-invasive sensitive tool for assessing the presence of LF in endemic areas. The aim of this review is to discuss the prospects, challenges and needs of xenomonitoring as a public health tool, in the post-MDA evaluation activities of national LF elimination programs. PMID- 26822602 TI - Lack of evidence for the efficacy of enhanced surveillance compared to other specific interventions to control neonatal healthcare-associated infection outbreaks. AB - BACKGROUND: Despite current prevention efforts, outbreaks of healthcare associated infections in neonatal units remain high globally, with a considerable burden of mortality and morbidity. METHODS: We searched Medline, Cochrane Library and Outbreak database to identify studies of neonatal healthcare-associated outbreaks between 2005 and 2015 that described interventions to control outbreaks. All studies were evaluated using the ORION guidance. RESULTS: Thirty studies were identified including 17 102 infants of whom 664 (3.9%) became infected. No single intervention was identified that reduced duration or mortality. Studies that introduced multiple interventions had significantly reduced case fatality ratio and outbreak duration compared to those that used basic surveillance only. Low and low-middle income countries reported the fewest interventions to control outbreaks and these studies were also associated with higher mortality than that found in middle and high income countries. CONCLUSIONS: Systematic reporting and formal evaluation of interventions used to reduce healthcare-associated neonatal infection outbreaks is key to identifying containment strategies worldwide. PMID- 26822603 TI - Vectorial capacity and vector control: reconsidering sensitivity to parameters for malaria elimination. AB - BACKGROUND: Major gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria. METHODS AND RESULTS: Using analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention. CONCLUSIONS: Reaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions. PMID- 26822604 TI - Understanding the relationship between prevalence of microfilariae and antigenaemia using a model of lymphatic filariasis infection. AB - BACKGROUND: Lymphatic filariasis is a debilitating neglected tropical disease that affects impoverished communities. Rapid diagnostic tests of antigenaemia are a practical alternative to parasitological tests of microfilaraemia for mapping and surveillance. However the relationship between these two methods of measuring burden has previously been difficult to interpret. METHODS: A statistical model of the distribution of worm burden and microfilariae (mf) and resulting antigenaemic and mf prevalence was developed and fitted to surveys of two contrasting sentinel sites undergoing interventions. The fitted model was then used to explore the relationship in various pre- and post-intervention scenarios. RESULTS: The model had good quantitative agreement with the data and provided estimates of the reduction in mf output due to treatment. When extrapolating the results to a range of prevalences there was good qualitative agreement with published data. CONCLUSIONS: The observed relationship between antigenamic and mf prevalence is a natural consequence of the relationship between prevalence and intensity of adult worms and mf production. The method described here allows the estimation of key epidemiological parameters and consequently gives insight into the efficacy of an intervention programme. PMID- 26822605 TI - The impact of rainfall and temperature on the spatial progression of cases during the chikungunya re-emergence in Thailand in 2008-2009. AB - BACKGROUND: In 2008, chikungunya virus (CHIKV) re-emerged in Thailand after more than a decade of absence. Cases first appeared in the extreme southern region of the country and advanced northward approx. 300 km over the next 18 months. The spatial advance of CHIKV cases appeared to occur at two rates, initially progressing slowly and then increasing in speed. We hypothesize that climatic variation affected the transmission of CHIKV in the country. METHODS: To determine the effect of climate on CHIKV transmission, we evaluated models where climate affects the transmission rate from mosquitoes to humans; extrinsic incubation period; fertility rate of mosquitoes; and the mortality rate of mosquito larvae. We compared these models to models that did not include climate effects. RESULTS: The inclusion of climate data greatly improved model fit with models assuming climate affected the fertility rate of mosquitoes providing the best fit to data. CONCLUSION: These results suggest that climatic variation contributed to the slower rate of incidence observed in March 2009. Overall, a gradient in transmission probability and mortality and fertility rates of mosquito is observed over the entire area with the most southern districts experiencing the most efficient transmission. PMID- 26822606 TI - Incidence and predictive factors of transaminase elevation in patients consulting for dengue fever in Cayenne Hospital, French Guiana. AB - BACKGROUND: The objective of the study was to determine the incidence of transaminase elevation during dengue, and its predictive factors. METHODS: In 2013, a longitudinal study was performed using data from all cases of dengue seen in Cayenne Hospital. Cox proportional modeling was used. Signs of major transaminase elevation were defined as an increase in aspartate amino transferase (AST) or alanine amino transferase (ALT) concentration over 10 times the normal value (10N). RESULTS: There were 1574 patients and 13 249 person-days of follow up. The incidence rate for signs of transaminase elevation (10N) was 0.55 per 100 person-days. Six patients had major transaminase elevation with AST>1000 units (0.43 per 1000 patient-days), and 73 patients (4.6%) developed transaminase elevation with AST >10N. The variables independently associated with major transaminase elevation were hyponatremia, low platelets, dehydration, hematocrit increase, food intolerance, positive nonstructural protein 1 (NS1), age over 15 years and the notion of paracetamol intake. CONCLUSIONS: Although very frequent, the incidence of major transaminase elevation was lower than reported elsewhere perhaps because of good access to care, or of the particular serotype causing this epidemic. The patients with transaminase elevation tended to be older, more severe and taking paracetamol. . PMID- 26822607 TI - Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine. AB - Dietary antigens are normally rendered nonimmunogenic through a poorly understood "oral tolerance" mechanism that involves immunosuppressive regulatory T (Treg) cells, especially Treg cells induced from conventional T cells in the periphery (pTreg cells). Although orally introducing nominal protein antigens is known to induce such pTreg cells, whether a typical diet induces a population of pTreg cells under normal conditions thus far has been unknown. By using germ-free mice raised and bred on an elemental diet devoid of dietary antigens, we demonstrated that under normal conditions, the vast majority of the small intestinal pTreg cells are induced by dietary antigens from solid foods. Moreover, these pTreg cells have a limited life span, are distinguishable from microbiota-induced pTreg cells, and repress underlying strong immunity to ingested protein antigens. PMID- 26822608 TI - The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring. AB - Viral infection during pregnancy has been correlated with increased frequency of autism spectrum disorder (ASD) in offspring. This observation has been modeled in rodents subjected to maternal immune activation (MIA). The immune cell populations critical in the MIA model have not been identified. Using both genetic mutants and blocking antibodies in mice, we show that retinoic acid receptor-related orphan nuclear receptor gamma t (RORgammat)-dependent effector T lymphocytes [for example, T helper 17 (TH17) cells] and the effector cytokine interleukin-17a (IL-17a) are required in mothers for MIA-induced behavioral abnormalities in offspring. We find that MIA induces an abnormal cortical phenotype, which is also dependent on maternal IL-17a, in the fetal brain. Our data suggest that therapeutic targeting of TH17 cells in susceptible pregnant mothers may reduce the likelihood of bearing children with inflammation-induced ASD-like phenotypes. PMID- 26822609 TI - 2.3 A resolution cryo-EM structure of human p97 and mechanism of allosteric inhibition. AB - p97 is a hexameric AAA+ adenosine triphosphatase (ATPase) that is an attractive target for cancer drug development. We report cryo-electron microscopy (cryo-EM) structures for adenosine diphosphate (ADP)-bound, full-length, hexameric wild type p97 in the presence and absence of an allosteric inhibitor at resolutions of 2.3 and 2.4 angstroms, respectively. We also report cryo-EM structures (at resolutions of ~3.3, 3.2, and 3.3 angstroms, respectively) for three distinct, coexisting functional states of p97 with occupancies of zero, one, or two molecules of adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS) per protomer. A large corkscrew-like change in molecular architecture, coupled with upward displacement of the N-terminal domain, is observed only when ATPgammaS is bound to both the D1 and D2 domains of the protomer. These cryo-EM structures establish the sequence of nucleotide-driven structural changes in p97 at atomic resolution. They also enable elucidation of the binding mode of an allosteric small-molecule inhibitor to p97 and illustrate how inhibitor binding at the interface between the D1 and D2 domains prevents propagation of the conformational changes necessary for p97 function. PMID- 26822610 TI - Steroids, drugs and stuttering priapism; the rock-and-roll lifestyle of a 24-year old man. AB - The authors present a case of a 24-year-old, poorly controlled insulin-dependent type 1 diabetic Caucasian man who presented to the emergency department, with a painful erection of 36 h duration that had failed to resolve with conservative management. This was the patient's seventh priapism, with his most recent attendance 1 week previously for which he underwent a distal cavernosal shunt. He admitted to taking several recreational drugs, including marijuana and cocaine, during the preceding few days, in addition to the long-term use of the oral anabolic steroid oxandrolone. He had no family history of sickle cell disease or trait. On examination, a tensely erect penis was noted. A diagnosis of stuttering priapism was made and 750 mL of blood subsequently drained via a distal corporoglandular shunt resulting in successful detumescence. PMID- 26822611 TI - Identifying Patients at High Risk of Loss of Response to Infliximab Maintenance Therapy in Paediatric Crohn's Disease. AB - BACKGROUND AND AIMS: Loss of response to infliximab resulting in discontinuation of therapy is a frequent problem encountered in paediatric Crohn's disease. Although identifying patients at risk of failure could have important implications for follow-up, literature in this area remains sparse. Our primary aim was to identify predictors of loss of response to infliximab among patients who were responders to induction. The secondary aim was to identify predictors of non-response to induction. METHODS: A retrospective cohort of patients with paediatric Crohn's disease treated with infliximab between 2000 and 2013 was followed until loss of response to infliximab or transfer to adult care. Predictors of response to induction therapy were studied by multivariate logistic regression. Time to treatment failure was analysed with a multivariate Cox model. RESULTS: Two-hundred and forty-eight patients were eligible for the study. Of these, 196 (79%) were responders to induction (57% clinical remission and 22% clinical response) and 52 (21%) were non-responders. Steroid resistance was the only variable independently associated with primary non-response (odds ratio [OR] 4.57, 95% confidence interval [CI] 1.67-12.50, p = 0.002). Thirty-one of the 196 responders discontinued infliximab due to loss of response after a mean of 1.6+/ 1.3 years of treatment. Predictors of loss of response were level of response to induction (clinical response vs clinical remission, hazard ratio [HR] 3.74, 95% CI 1.80-7.80, p = 0.0004) and isolated colonic disease (HR 2.72, 95% CI 1.30 5.71, p = 0.008). CONCLUSIONS: Patients who fail to achieve clinical remission after induction and/or who have isolated colonic disease are at increased risk of loss of response to infliximab. PMID- 26822612 TI - Controversies in Pouch Surveillance for Patients with Inflammatory Bowel Disease. AB - CASE 1: Following 2 years of rectal blood loss, a 31-year-old male was diagnosed with ulcerative pancolitis in 1978. Initial treatment consisted of both topical and systemic 5-aminosalicylic acids [5-ASAs], and remission was achieved. In both 1984 and 1986 he was hospitalised due to exacerbations necessitating treatment with intravenous corticosteroids. The following years went well, without disease activity, under treatment with 5-ASA. In 1997, at the age of 50 years, a surveillance colonoscopy showed a stenotic process with a macroscopic irregularity in the sigmoid region. Histology revealed at least high-grade dysplasia [HGD] and signs of an invasive growth pattern which could indicate colorectal cancer [CRC]. The patient underwent restorative proctocolectomy with ileal pouch-anal anastomosis [IPAA]. Histology of the resection specimen confirmed active inflammation in the colon and rectum and a carcinoma in situ was identified in the sigmoid colon without invasive growth. This patient did not have significant comorbidities-for example primary sclerosing cholangitis [PSC] and the CRC family history was negative. What pouch surveillance strategy should be recommended? CASE 2: A 34-year-old man presented at our inflammatory bowel disease [IBD] centre with ulcerative proctitis. Ten years later, after an initially mild disease course, his disease progressed to a pancolitis. An 11-year period with multiple exacerbations [on average every 2 year, including hospitalisation] followed and treatment consisted of topical and systemic 5-ASAs with intermittent corticosteroids. In 1998, at the age of 65 years, a two-stage restorative proctocolectomy with IPAA was performed due to disease activity refractory to systemic corticosteroids. The colectomy specimen confirmed the diagnosis of ulcerative pancolitis without evidence for colorectal dysplasia or carcinoma. Other than steroid-induced diabetes mellitus, this patient had no comorbidities. His father died from CRC at unknown age. What pouch surveillance strategy should be recommended? PMID- 26822613 TI - AVX-470, an Orally Delivered Anti-Tumour Necrosis Factor Antibody for Treatment of Active Ulcerative Colitis: Results of a First-in-Human Trial. AB - BACKGROUND AND AIMS: AVX-470 is an oral, polyclonal bovine-derived anti-tumour necrosis factor (TNF) antibody in development for treatment of inflammatory bowel disease (IBD). AVX-470 neutralizes TNF locally in the gastrointestinal tract, minimizing systemic exposure. This was a double-blind, placebo-controlled, first in-human trial designed to assess the safety, pharmacokinetics, immunogenicity and preliminary efficacy of 4 weeks of AVX-470 in patients with active ulcerative colitis (UC). METHODS: Thirty-seven patients with active UC were randomized and 36 received AVX-470 (0.2, 1.6 or 3.5g/day) or placebo over 4 weeks. Endoscopic activity was assessed by colonoscopy pre- and post-treatment. The primary endpoint was safety. Secondary endpoints included pharmacokinetics and immunogenicity. Clinical and endoscopic response and remission were assessed as exploratory endpoints. RESULTS: Thirty-three (92%) patients completed treatment and follow-up. The incidence of adverse events was similar across treatment groups and no allergic reactions or opportunistic infections were reported. AVX 470 therapy did not induce human anti-bovine antibodies (HABA). Bovine immunoglobulin (Ig) with TNF binding capacity was detected in stool, while bovine Ig levels in serum were low. Across all AVX-470 doses, 25.9% of patients achieved clinical response compared with 11.1% on placebo, with greatest improvements in the 3.5g/day group associated with proximal colon endoscopic improvement and reductions in serum CRP and IL-6. CONCLUSIONS: AVX-470 was safe and well tolerated in this first-in-human trial in UC, with efficacy trends for clinical, endoscopic and biomarker endpoints in the highest dose group (3.5g/day). Results suggest benefit of an orally delivered locally active agent in moderate to severe UC. CLINICAL TRIAL REGISTRATION NUMBER: This trial was registered with Clinicaltrials.gov as study NCT01759056 and with EudraCT as study 2012-004859-27. PMID- 26822614 TI - Assessing the twinning model in the Rwandan Human Resources for Health Program: goal setting, satisfaction and perceived skill transfer. AB - BACKGROUND: Because of the shortage of health professionals, particularly in specialty areas, Rwanda initiated the Human Resources for Health (HRH) Program. In this program, faculty from United States teaching institutions (USF) "twin" with Rwandan Faculty (RF) to transfer skills. This paper assesses the twinning model, exploring USF and RF goal setting, satisfaction and perceptions of the effectiveness of skill transfer within the twinning model. METHODS: All USF and RF in the HRH Program from August 2012-May 2014 were invited to participate. An 85-item questionnaire for USF and 71-item questionnaire for RF were administered via Survey Monkey in April and May 2014. Associations among primary outcomes were assessed and factors related with outcomes were modeled using logistic regression. RESULTS: Most RF and USF reported setting goals with their twin (89% and 71%, respectively). Half of RF (52%) reported effective skill transfer compared to 10% of USF. Only 38% of RF and 28% of USF reported being very satisfied with the twinning model. There was significant overlap in the three operational outcomes. For RF, the following factors were associated with outcomes: for effective skill transfer, being able to communicate in a common language and working at a nursing site outside of Kigali; and for satisfaction, 7+ years of professional experience and being part of a male RF-female USF twin pair. For USF, the following factors were associated with outcomes: for setting goals, prior teaching experience; and for satisfaction, experience in low resource settings for one month or less and feeling that HRH promotes a culture of respect. CONCLUSIONS: Twinning is the cornerstone of the HRH Program in Rwanda. These findings helped the HRH team identify key areas to improve the twinning experience including better recruitment and orientation of USF and RF, consideration of additional factors during the twinning process, provide language training support, facilitate joint twin activities and cross-cultural training and improve the site leadership buy-in and support of the program. These results can inform other programs using twinning to develop skills in the health workforce. PMID- 26822615 TI - Diarrheagenic pathogens in adults attending a hospital in Singapore. AB - BACKGROUND: Singapore's diarrhoeal notification system is based on specific pathogens. Official data may thus be skewed towards notifiable diseases. Limited information is available on the profiles of aetiological agents responsible for acute gastroenteritis (AGE) cases, especially among the adult population. To understand the frequency and distribution of potential causative agents of diarrheal disease in Singapore, we screened adults' stool samples collected from a large public hospital. METHODS: The stool samples were screened for 18 diarrheagenic pathogens using a combination of commercial multiplex polymerase chain reaction (PCR), in-house singleplex PCR and immunochromatographic assays. One hundred adult faecal samples that were collected from October 2013 to January 2014 for routine diagnostic purposes and submitted for culture at Tan Tock Seng Hospital, Singapore were used. RESULTS: Pathogens were detected in 32% of the samples. The predominant organisms encountered were norovirus genogroup II (11%), Aeromonas spp. (9%) and Campylobacter spp. (5%). One sample was positive for both verocytotoxigenic E. coli (VTEC) and E. coli O157:H7. Two other samples were positive for VTEC only, and one other sample was positive for E. coli O157:H7 only. Astrovirus, C. perfringens, Shigella spp. and toxigenic C. difficile were each detected in 2% of the samples. Cryptosporidium parvum, Giardia lamblia, group A rotavirus, Salmonella spp. and Vibrio spp. were each detected in 1% of the samples. No L. monocytogenes, Y. enterocolitica, enteric adenovirus, or norovirus genogroup I were detected. CONCLUSION: Our preliminary findings suggest that pathogens causing non-notifiable diseases might have contributed considerably to the adult hospitalised AGE cases. However, as the samples were from an adult hospital, the data obtained may not be representative of the whole community. Thus, a larger study to collect clinical samples and risk exposure data from primary healthcare clinics and children hospital is planned for, to gain a more holistic perspective on the epidemiology of AGE in Singapore. A larger study may also offer valuable insights for improving the approach of microbiological surveillance of food, as well as strategizing inspection efforts along the food supply chain by public health authorities. PMID- 26822617 TI - Core@shell Poly(n-butylacrylate)@polystyrene Nanoparticles: Baroplastic Force Responsiveness in Presence of Strong Phase Separation. AB - Poly(n-butylacrylate)@polystyrene nanoparticles behaving as a capsule-based sealing nanoadditive are synthesized through an optimized semicontinuous emulsion polymerization protocol. Solid state time-domain (1)H-NMR and (13)C magic angle spinning (MAS) NMR analysis suggest strong phase separation. Line width of (13)C resonances in cross polarization and single pulse experiment MAS-NMR spectra indicates that the peculiar mobility of each phase is preserved at the nanoscale. Atomic force spectroscopy (AFM) shows the permanence of spherical shape in absence of solvent (i.e., subsequent to strong capillary and surface forces) up to moderate external load, as well as the possibility of plastically deforming the polystyrene shell and ultimately triggering the nanoparticle flow at higher force loads. The breakdown characteristic of the nanoparticle shows for the first time baroplastic behavior on a single particle with precise biphasic core@shell morphology. PMID- 26822616 TI - High-resolution identification and abundance profiling of cassava (Manihot esculenta Crantz) microRNAs. AB - BACKGROUND: Small RNAs (sRNAs) are endogenous sRNAs that play regulatory roles in plant growth, development, and biotic and abiotic stress responses. In plants, one subset of sRNAs, microRNAs (miRNAs) exhibit tissue-differential expression and regulate gene expression mainly through direct cleavage of mRNA or indirectly via production of secondary phased siRNAs (phasiRNAs) that silence cognate target transcripts in trans. RESULTS: Here, we have identified cassava (Manihot esculenta Crantz) miRNAs using high resolution sequencing of sRNA libraries from leaf, stem, callus, male and female flower tissues. To analyze the data, we built a cassava genome database and, via sequence analysis and secondary structure prediction, 38 miRNAs not previously reported in cassava were identified. These new cassava miRNAs included two miRNAs not previously been reported in any plant species. The miRNAs exhibited tissue-differential accumulation as confirmed by quantitative RT-PCR and Northern blot analysis, largely reflecting levels observed in sequencing data. Some of the miRNAs identified were predicted to trigger production of secondary phased siRNAs (phasiRNAs) from 80 PHAS loci. CONCLUSIONS: Cassava is a woody perennial shrub, grown principally for its starch rich storage roots, which are rich in calories. In this study, new miRNAs were identified and their expression was validated using qRT-PCR of RNA from five different tissues. The data obtained expand the list of annotated miRNAs and provide additional new resources for cassava improvement research. PMID- 26822618 TI - Risk of Respiratory Syncytial Virus Infection in Cyanotic Congenital Heart Disease in a Subtropical Area. AB - OBJECTIVE: To compare the risk of respiratory syncytial virus (RSV)-associated hospitalization and analyze the epidemiology of RSV infection in patients with cyanotic and acyanotic congenital heart disease (CHD), we analyzed the nationwide health insurance database from 2005-2010. STUDY DESIGN: This study included 1050 patients with cyanotic CHD and 7077 patients with acyanotic CHD. Patients with acyanotic CHD were further classified into hemodynamically significant (hs) acyanotic and non-hs-acyanotic groups according to whether they underwent surgery or took at least 2 anticongestive medications. RESULTS: RSV-associated hospitalization was higher in the cyanotic group than in hs-acyanotic and non-hs acyanotic groups both before 1 year of age (4.8% vs 2.1% vs 1.5%, P < .001) and between 1 and 2 years of age (0.9% vs 0.56% vs 0.14%, P = .003). The hospitalization duration, intensive care, ventilator support prevalence, hospitalization cost, and mortality rate were significantly higher in the cyanotic group than in the other 2 groups. Logistic regression revealed that cyanotic CHD was the most significant risk factor for the ventilator support and RSV-associated mortality. In both patients with cyanotic and acyanotic CHD, RSV associated hospitalization rate was higher in patients aged younger than 1 year and in spring and autumn in Taiwan, a subtropical country. CONCLUSIONS: The results show that patients with cyanotic CHD have a higher risk of severe RSV infection than do those with acyanotic CHD. RSV prophylaxis is more important and may reduce costs more for patients with cyanotic CHD. PMID- 26822620 TI - Improving Outcomes and Promoting Quality in Otolaryngology-Beyond the National Surgical Quality Improvement Program. PMID- 26822619 TI - BPA-toxicity via superoxide anion overload and a deficit in beta-catenin signaling in human bone mesenchymal stem cells. AB - Bisphenol A (BPA), used in the manufacture of products based on polycarbonate plastics and epoxy resins, is well known as an endocrine-disrupting monomer. In the current study, BPA increased cytotoxicity in hBMSCs in a dose- and time dependent manner, concomitantly with increased lipid peroxidation. Increased cell death in BPA-treated cells was markedly blocked by pretreatment with the superoxide dismutase mimetic MnTBAP and MnTMPyP, but not by catalase, glutathione, the glutathione peroxidase mimetic ebselen, the NOS inhibitor NAME, or the xanthine oxidase inhibitor allopurinol. Furthermore, the decline in nuclear beta-catenin and cyclin D1 levels in hBMSCs exposed to BPA was reversed by MnTBAP treatment. Finally, treatment of hBMSCs with the GSK3beta inhibitor LiCl2 increased nuclear beta-catenin levels and significantly attenuated cytotoxicity compared with BPA treatment. Our current results in hBMSCs exposed to BPA suggest that BPA causes a disturbance in beta-catenin signaling via a superoxide anion overload. (c) 2016 The Authors Environmental Toxicology Published by Wiley Periodicals, Inc. Environ Toxicol 32: 344-352, 2017. PMID- 26822622 TI - Microphase separation of short wormlike diblock copolymers with a finite interaction range. AB - We investigate several structural properties of low-molecular weight AB diblock copolymer melts, focusing on a number of features that substantially deviate from those of high-molecular weight copolymer melts. The study is based on the wormlike chain formalism aided by random phase approximation and self-consistent field theory. We examine the effects that stemmed from both the finite molecular weight and the finite interaction range between unlike AB monomers. The latter yields profound effects on systems consisting of short wormlike block copolymers. The noticeable shift of the order-disorder transition point is discussed. Attention is also paid to the strong-segregation regime, where low molecular weight polymers are subject to finite stretchability. PMID- 26822621 TI - The aberrantly expressed miR-193b-3p contributes to preeclampsia through regulating transforming growth factor-beta signaling. AB - Preeclampsia (PE) is a leading cause of maternal mortality worldwide. Several studies have detected some differentially expressed microRNAs in the preeclamptic placenta, but few of the identified microRNAs demonstrated consistent findings among different research studies. In this study, high-throughput microRNA sequencing (HTS) of 9 preeclamptic and 9 normal placentas was performed. Seventeen microRNAs were identified to be up-regulated, and 8 down-regulated in preeclamptic placentas. Eight differentially expressed microRNAs except one identified in our study were determined to be consistent with at least one previous study, while sixteen were newly found. We performed qRT-PCR with independent 22 preeclamptic placentas and 20 control placentas to verify the differentially expressed microRNAs, and ten microRNAs were validated. The predicted target genes of the aberrantly expressed miR-193b-3p were enriched in the following gene ontology categories: cell motility and migration, cell proliferation and angiogenesis. We also found that miR-193b-3p significantly decreased the migration and invasion of trophoblast (HTR-8/SVneo) cells and that miR-193b-3p could regulate trophoblasts migration and invasion through binding onto the 3'UTR target site of TGF-beta2. In conclusion, we identified a list of differentially expressed microRNAs in PE placentas by HTS and provided preliminary evidence for the role of miR-193b-3p in the pathogenesis of preeclampsia. PMID- 26822623 TI - User evaluation of patient counselling, combining nurse consultation and eHealth in hand eczema. AB - BACKGROUND AND OBJECTIVE: This study reports the findings from a user evaluation of a counselling programme for hand eczema patients in which face-to-face encounters were supplemented with user access to a new website. PATIENTS AND METHODS: Patients treated for hand eczema in two different settings were included consecutively. Website utilization was examined by use of the transaction log. Comparisons were made between participants who used the website and those who did not. The patients' perspectives were explored by the use of interviews. RESULTS: Among potential website users (n = 140), 88 patients (63%) had an average of 5.1 site visits. At follow-up, the website users had improved more in quality of life (p = 0.014), current burden of disease (p = 0.053), and itching (p = 0.042). The website users reported more changes in habits than did the non-website users (p = 0.024). No differences in clinical severity of hand eczema were found. The interviewees were generally satisfied with the counselling and the website. The strict log-on procedures were considered to be an obstacle to using the site. The consecutive inclusion of participants was considered to be a barrier to engagement in the dialogue forum. CONCLUSIONS: The website users benefited from the website, although this was not substantiated by clinical measurements. The trial design partly hampered website utilization. An initial feasibility study could have been warranted. PMID- 26822624 TI - Relationship between restraint use, engagement in social activity, and decline in cognitive status among residents newly admitted to long-term care facilities. AB - AIM: Declining cognitive function can negatively affect residents' quality of life (QOL) in long-term care facilities (LTCFs). The present study examined the role of physical restraint use, use of antipsychotic medications, and engagement in social activities to affect change in cognitive status and drive cognitive decline among residents newly admitted to a LTCF. METHODS: Secondary data analysis used interRAI Minimum Data Set 2.0 data gathered at admission and first follow-up assessment (n = 111,052). The interRAI Minimum Data Set 2.0 collects comprehensive information as part of regular clinical care, and is mandated for all LTCF in Ontario, Canada. Bivariate and logistic regression analyses investigated the roles of physical restraint use, antipsychotic medication use and social engagement affecting cognition, and were stratified based on the presence/absence of diagnosis of dementia. RESULTS: At follow up, 16.1% of residents (n = 16 414) showed decline in cognition. Residents with one or more physical restraints (chair, trunk and limb) were at increased risk for cognitive decline evidenced among residents with and without a diagnosis of dementia. Antipsychotic medication use did not emerge as a strong predictor of cognitive decline. Social engagement was protective against cognitive decline, and more pronounced for residents without a diagnosis of dementia. CONCLUSION: Physical restraint use should be avoided, or used as a last resort. LTCFs should prioritize resident engagement in social activities in either formal activities or ad hoc, as soon as possible on entry to the LTCFs. Prioritizing social networks and greater participation in activities might decrease the risk for cognitive decline, thereby improving or maintaining resident quality of life. Geriatr Gerontol Int 2017; 17: 246-255. PMID- 26822626 TI - Columellar Incision Scars in Asian Patients Undergoing Open Rhinoplasty. AB - IMPORTANCE: An open approach has been adopted for rhinoplasty because of its wide and undistorted exposure. The formation of a columellar incision scar is the main drawback of this approach. OBJECTIVE: To evaluate the incidence and evolution of and risk factors for columellar incision scars in an Asian population. DESIGN, SETTING, AND PARTICIPANTS: A retrospective case series of 529 patients who underwent open rhinoplasty was performed in a tertiary care referral center in South Korea from January 1, 2011, to May 31, 2014. Problematic transcolumellar incision scars were categorized into wide and depressed, notching, and hyperpigmented wound types. Follow-up was complete on January 28, 2015, and data were assessed from July 1, 2014, to May 29, 2015. MAIN OUTCOMES AND MEASURES: The incidence of each problematic scar and the time course of erythema evolution were evaluated. Factors affecting the formation of a problematic scar were also evaluated. RESULTS: Of 529 patients (176 female and 353 male patients; mean age, 31 [range, 5-70] years), 234 patients with at least 6 months of follow-up underwent evaluation for a problematic scar. Fourteen of the 234 patients (6.0%) had problematic incision scarring (wide and depressed wound, 4 [1.7%]; notching wound, 3 [1.3%]; hyperpigmentation, 4 [1.7%]; marginal incision hypertrophic scar, 2 [0.8%]; and columellar skin necrosis, 1 [0.4%]). Of the 243 patients with regular follow-up who underwent evaluation for erythema evolution, erythematous wounds were found in almost all in the immediate postoperative period and had normalized by a mean (SD) of 66.7 (37.4) postoperative days. Use of costal cartilage as tip graft material was associated with a problematic incision scar (2 of 25 patients [8.0%] vs 6 of 180 patients with other graft material [3.3%]; P = .02). CONCLUSIONS AND RELEVANCE: In this cohort of Asian patients, the incisions used for an open rhinoplasty approach had some problems. However, the low incidence of problematic scars indicates that open rhinoplasty should not be discouraged because of the incision scar. LEVEL OF EVIDENCE: 4. PMID- 26822625 TI - Robotic Surgery for Thoracic Disease. AB - Robotic surgeries have developed in the general thoracic field over the past decade, and publications on robotic surgery outcomes have accumulated. However, controversy remains about the application of robotic surgery, with a lack of well established evidence. Robotic surgery has several advantages such as natural movement of the surgeon's hands when manipulating the robotic arms and instruments controlled by computer-assisted systems. Most studies have reported the feasibility and safety of robotic surgery based on acceptable morbidity and mortality compared to open or video-assisted thoracic surgery (VATS). Furthermore, there are accumulated data to indicate longer operation times and shorter hospital stay in robotic surgery. However, randomized controlled trials between robotic and open or VATS procedures are needed to clarify the advantage of robotic surgery. In this review, we focused the literature about robotic surgery used to treat lung cancer and mediastinal tumor. PMID- 26822627 TI - Editorial Comment from Dr Sakano and Dr Matsuyama to Impact of multimodal treatment on prognosis for patients with metastatic upper urinary tract urothelial cancer: Subanalysis of the multi-institutional nationwide case series study of the Japanese Urological Association. PMID- 26822628 TI - Towards understanding the biological function of the unusual chaperonin Cpn60.1 (GroEL1) of Mycobacterium tuberculosis. AB - The 60 kDa heat shock proteins, also known as Cpn60s (GroELs) are components of the essential protein folding machinery of the cell, but are also dominant antigens in many infectious diseases. Although generally essential for cellular survival, in some organisms such as Mycobacterium tuberculosis, one or more paralogous Cpn60s are known to be dispensable. In M. tuberculosis, Cpn60.2 (GroEL2) is essential for cell survival, but the biological role of the non essential Cpn60.1 (GroEL1) is still elusive. To understand the relevance of Cpn60.1 (GroEL1) in M. tuberculosis physiology, detailed transcriptomic analyses for the wild type H37Rv and cpn60.1 knockout (groEL1-KO) were performed under in vitro stress conditions: stationary phase, cold shock, low aeration, mild cold shock and low pH. Additionally, the survival of the groEL1-KO was assessed in macrophages at multiplicity of infection (MOI) of 1:1 and 1:5. We observed that survival under low aeration was significantly compromised in the groEL1-KO. Further, the gene expression analyses under low aeration showed change in expression of several key virulence factors like two component system PhoP/R and MprA/B, sigma factors SigM and C and adversely affected known hypoxia response regulators Rv0081, Rv0023 and DosR. Our work is therefore suggestive of an important role of Cpn60.1 (GroEL1) for survival under low aeration by affecting the expression of genes known for hypoxia response. PMID- 26822629 TI - The discovery and characterization of a novel scaffold as a potent hepatitis C virus inhibitor. AB - HCV infections are a major global health concern. Although direct acting antiviral agents have significantly improved the response rate of anti-HCV therapy, they also suffer from drug resistance, unfavorable pharmacokinetic profiles and high costs. Thus, it is still highly desirable to develop new anti HCV therapeutics. Herein a novel anti-HCV benzothiazole scaffold was discovered by phenotypic screening. Further target characterization and structural optimization studies revealed that the benzothiazole-disulfoamide derivatives were potent anti-HCV molecules with good selectivity and acted by targeting NS5A. PMID- 26822630 TI - Pharmacodynamic Effects of Low-Dose Pioglitazone in Patients with the Metabolic Syndrome without Diabetes Mellitus. AB - STUDY OBJECTIVE: To determine the effects of low-dose pioglitazone on plasma adipocyte-derived cytokines, high-sensitivity C-reactive protein (hs-CRP), and components of the metabolic syndrome in adults with the metabolic syndrome without diabetes mellitus. DESIGN: Prospective, randomized, double-blind, placebo controlled study. SETTING: University of Colorado Clinical and Translational Research Center. PATIENTS: Thirty-two men and women, aged 30-60 years, without diabetes who had a clinical diagnosis of the metabolic syndrome, as defined by the American Heart Association/National Heart, Lung, and Blood Institute criteria. INTERVENTION: Patients were randomly assigned to receive oral pioglitazone 7.5 mg daily or matching placebo for 8 weeks. MEASUREMENTS AND MAIN RESULTS: The primary end point was the change in plasma high-molecular-weight (HMW) adiponectin level from baseline to week 8. Other end points were changes in plasma total adiponectin, omentin, and hs-CRP levels, and changes in components of the metabolic syndrome (e.g., insulin sensitivity) from baseline to week 8. Pioglitazone was associated with a significant increase in plasma HMW adiponectin from baseline to week 8 compared with placebo (+47% vs -10%, p<0.001). Insulin sensitivity increased significantly from baseline to week 8 in the pioglitazone group (+88%, p=0.02) but not in the placebo group (+15%, p=0.14). Change in HMW adiponectin was significantly correlated with the change in insulin sensitivity in the pioglitazone group (r = 0.784, p=0.003). No significant differences in mean percentage changes in plasma total adiponectin, omentin, and hs-CRP levels were observed between the pioglitazone and placebo groups. Likewise, changes in body weight, insulin sensitivity, glucose, lipids, and blood pressure did not differ significantly between the groups. CONCLUSION: Low-dose pioglitazone favorably modulates plasma HMW adiponectin, which was associated with an improvement in insulin sensitivity, in patients with the metabolic syndrome without diabetes. PMID- 26822631 TI - Combining Biomimetic Block Copolymer Worms with an Ice-Inhibiting Polymer for the Solvent-Free Cryopreservation of Red Blood Cells. AB - The first fully synthetic polymer-based approach for red-blood-cell cryopreservation without the need for any (toxic) organic solvents is reported. Highly hydroxylated block copolymer worms are shown to be a suitable replacement for hydroxyethyl starch as a extracellular matrix for red blood cells. When used alone, the worms are not a particularly effective preservative. However, when combined with poly(vinyl alcohol), a known ice-recrystallization inhibitor, a remarkable additive cryopreservative effect is observed that matches the performance of hydroxyethyl starch. Moreover, these block copolymer worms enable post-thaw gelation by simply warming to 20 degrees C. This approach offers a new solution for both the storage and transport of red blood cells and also a convenient matrix for subsequent 3D cell cultures. PMID- 26822632 TI - Non-random walk diffusion enhances the sink strength of semicoherent interfaces. AB - Clean, safe and economical nuclear energy requires new materials capable of withstanding severe radiation damage. One strategy of imparting radiation resistance to solids is to incorporate into them a high density of solid-phase interfaces capable of absorbing and annihilating radiation-induced defects. Here we show that elastic interactions between point defects and semicoherent interfaces lead to a marked enhancement in interface sink strength. Our conclusions stem from simulations that integrate first principles, object kinetic Monte Carlo and anisotropic elasticity calculations. Surprisingly, the enhancement in sink strength is not due primarily to increased thermodynamic driving forces, but rather to reduced defect migration barriers, which induce a preferential drift of defects towards interfaces. The sink strength enhancement is highly sensitive to the detailed character of interfacial stresses, suggesting that 'super-sink' interfaces may be designed by optimizing interface stress fields. Such interfaces may be used to create materials with unprecedented resistance to radiation-induced damage. PMID- 26822633 TI - Warfarin initiation nomograms for venous thromboembolism. AB - BACKGROUND: Venous thromboembolism (VTE) is a common condition in hospital patients. Considerable controversy is ongoing regarding optimal initial warfarin dosing for patients with acute deep venous thrombosis (DVT) and pulmonary embolism (PE). Achieving a therapeutic international normalized ratio (INR) with warfarin as soon as possible is important because this minimizes the duration of parenteral medication necessary to attain immediate anticoagulation, and it potentially decreases the cost and inconvenience of treatment. Although a 5-mg loading-dose nomogram tends to prevent excessive anticoagulation, a 10-mg loading dose nomogram may achieve a therapeutic INR more quickly. This is an update of a review first published in 2013. OBJECTIVES: To evaluate the efficacy of a 10-mg warfarin nomogram compared with a 5-mg warfarin nomogram among patients with VTE. SEARCH METHODS: For this update the Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register (last searched September 2015) and the Cochrane Register of Studies (CENTRAL (2015, Issue 8). Clinical trials databases were also searched. The review authors searched PubMed (last searched 11 June 2015) and LILACS (last searched 11 June 2015). In addition, the review authors contacted pharmaceutical companies. SELECTION CRITERIA: Randomized controlled studies comparing warfarin initiation nomograms of 10 and 5 mg in patients with VTE. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. The review authors contacted study authors for additional information. MAIN RESULTS: Four trials involving 494 participants were included. Three studies involving 383 participants provided data on the proportion of participants who had achieved a therapeutic INR by day five. Significant benefit of a 10-mg warfarin nomogram was observed (risk ratio (RR) 1.27, 95% confidence interval (CI) 1.05 to 1.54; moderate quality evidence), although with substantial heterogeneity (I(2) = 90%). The review authors analyzed each study separately because it was not possible to perform a subgroup analysis by inpatient or outpatient status. One study showed significant benefit of a 10-mg warfarin nomogram for the proportion of outpatients with VTE who had achieved a therapeutic INR by day five (RR 1.78, 95% CI 1.41 to 2.25), with the number needed to treat for an additional beneficial outcome (NNTB = 3, 95% CI 2 to 4); another study showed significant benefit of a 5-mg warfarin nomogram in outpatients with VTE (RR 0.58, 95% CI 0.36 to 0.93) with NNTB = 5 (95% CI 3 to 28); a third study, consisting of both inpatients and outpatients, showed no difference (RR 1.08, 95% CI 0.65 to 1.80).No difference was observed in recurrent venous thromboembolism at 90 days when the warfarin nomogram of 10 mg was compared with the warfarin nomogram of 5 mg (RR 1.48, 95% CI 0.39 to 5.56; 3 studies, 362 participants, low quality evidence); no difference was observed in major bleeding at 14 to 90 days (RR 0.97, 95% CI 0.27 to 3.51; 4 studies, 494 participants, moderate quality evidence). No difference was observed in minor bleeding at 14 to 90 days (RR 0.52, 95% CI 0.15 to 1.83; 2 studies, 243 participants, very low quality evidence) or in length of hospital stay (mean difference (MD) -2.3 days, 95% CI -7.96 to 3.36; 1 study, 111 participants, low quality evidence). AUTHORS' CONCLUSIONS: In patients with acute thromboembolism (DVT or PE) aged 18 years or older, considerable uncertainty surrounds the use of a 10-mg or a 5-mg loading dose for initiation of warfarin to achieve an INR of 2.0 to 3.0 on the fifth day of therapy. Heterogeneity among analyzed studies, mainly caused by differences in types of study participants and length of follow up, limits certainty surrounding optimal warfarin initiation nomograms. PMID- 26822634 TI - [Recent progress in international public health]. AB - This paper summarizes the recent progress in international public health in terms of public health challenges, infectious diseases prevention and control, disease surveillance, chronic and non-communicable disease prevention and treatment, global health, health literacy and precision medicine for the purpose to provide reference for the improvement of public health in China. PMID- 26822635 TI - [Analysis on violence injury incidence and prevention in China]. AB - OBJECTIVE: To understand the incidence of violence injury and its prevention in China, and provide reference for the prevention and control of violence injury. METHODS: The violence injury data in China were collected from national death surveillance data set (2006-2013) and national injury surveillance system (2013) for the descriptive epidemiological analysis on the incidence of violence injury and related death. The laws and policies about violence injury prevention, related data collection capacity and violence injury prevention programs in China were described. RESULTS: The violence injury mortality declined by 46.3% during 2006-2013 from 1.21/100000 to 0.65/100000. The incidence of violence injury death in males peaked in age group 30-34 years (1.42/100000), and it was low in age group<15 years. Three peaks of violence injury death were found in females, i.e. 0.84/100000 in infants, 0.72/100000 in age group 30-34 years and 1.18/100000 in age group>=85 years. The laws and policies about violence injury prevention were imperfect, and the data about violence injury were limited. Most prevention programs were limited in scale and duration. CONCLUSIONS: The crude and standardized violence injury mortality declined in China during 2006-2013. It is necessary to conduct gender specific prevention strategies and improve the related law and policy development, data collection and prevention service. PMID- 26822636 TI - [Analysis on influencing factors for child restraint system use in Shanghai and Shenzhen, China]. AB - OBJECTIVE: To understand the factors related with child restraint system (CRS) use, and provide evidence for the development of appropriate intervention measures to promote the use of CRS for the protection of child passengers' safety. METHODS: Self-administrated questionnaire survey was conducted among 0-6 years old children's parents who owned private cars selected through stratified cluster random sampling in Shanghai and Shenzhen to collect date about CRS use and related factors. Group discussion was conducted among some of the parents randomly selected to further understand the reasons for using or not using CRS. RESULTS: Of 7528 parents surveyed, 39.23% (2820/7189) reported to have CRS and 17.14% (1232/7189) reported consistent use of CRS. Multivariate analysis indicated that young age of children, high level of education of parents, good family economic status, awareness of importance of children's safety were the positive factors for CRS use. The frequency and distance of children'car taking and the seatbelt use of drivers significantly influenced the CRS use. The main reasons for not purchasing CRS included limited car space (53.33%, 2329/4 367), low frequency of children car taking (48.55%, 2120/4367), difficulty in installation (42.25%, 1845/4367), high cost (38.58%, 1685/4367), and unreliable quality (31.03%, 1355/4367). The main reasons for not using CRS included children's refusal (67.36%, 293/435), short travel distance (53.79%, 234/435), difficulty in installation or use (53.10%, 231/435), limited car space (32.41%, 141/435), and unnecessary (25.75%, 112/435). CONCLUSIONS: Parents have gaps and misunderstandings in using CRSs to protect child passengers safety. There are demands of technical guiding service in use of CRS. Integrated intervention measures should be implemented targeting at the identified barriers and needs in CRS use to promote child passenger safety, which include strengthening the propaganda and education, promoting the legislation and law enforcement, strengthening market supervision, establishing CRS related services site, exploring the rental market, etc. PMID- 26822637 TI - [Epidemiological characteristics of product harm cases in 32 hospitals in 11 areas in China, 2012-2014]. AB - OBJECTIVE: To understand the epidemiological characteristics of product harm cases in 32 hospitals in 11 areas in China from 2012 to 2014 and provide the basic data to support for product-specific survey, product harm early warning and the assessment of product safety. METHODS: The descriptive epidemiologic analysis was conducted by using the surveillance data of product harm collected from 32 hospitals in 11 areas in China during 2012-2014. RESULTS: A total of 208 784 product harm cases were reported in the 32 hospitals during 2012-2014, accounting for 19.50% of total harm cases during the same period. A total of 222 401 cases (times) of product harm were reported. For all the product harms, the top five products causing harms were transportation equipment except motor vehicle (36.55%), motor vehicle (21.50%), other products (20.84%), furniture (7.21%) and food, medicine and related products (5.18%). Both the case number and times of product harm were higher in males than in females. Males aged 25-44 years might be at greater risk for product harm. Most product harms, i.e. bruise, were caused by blunt force on heads. CONCLUSIONS: The epidemiologic characteristics of product harm varied with products. It is necessary to take targeted intervention measures to prevent product harm. PMID- 26822638 TI - [Epidemiologic characteristics of fall in old population: Results from national injury surveillance in China, 2014]. AB - OBJECTIVE: To understand the epidemiologic characteristics of fall in people aged >=60 years in China and provide evidence for the development of prevention and control measures of fall in old population. METHODS: Data of fall in people aged >=60 years in China in 2014 were collected from National Injury Surveillance System (NISS) for the descriptive epidemiologic analysis. RESULTS: A total of 41,073 fall cases were reported in people aged >=60 years in 2014, accounting for 52.81% of total unintentional injuries in this population. The fall to unintentional injury ratio was higher in older age group. The gender ratio of fall cases was 0.77 and the proportion of females increased with age. Fall mainly occurred during 8:00-11:59 in the morning (33.31%). The top three places where fall might occur were home (55.66%), public residential places (20.52%) and roads (11.64%). Recreational activity (68.94%) and housework/study (16.14%) were the major causes for fall. The common injury sites were low limbs (29.28%), head (24.40%) and body (20.04%), while the common injuries caused by fall were bruise (45.76%) and fractures (29.52%), spain/strain (13.28%). The fall injuries were mainly mild (64.20%), while more moderate and serious fall injuries occurred in older age group. CONCLUSION: Fall is the major cause of injury in old population in China, and the proportion of fall in unintentional injury in this population increased with age, indicating that the prevention of fall in old population should be strengthened. PMID- 26822639 TI - [Prevalence of myopia and influencing factors among primary and middle school students in 6 provinces of China]. AB - OBJECTIVE: To understand the prevalence of myopia in primary and middle school students in 6 provinces and the possible influencing factors. METHODS: Primary and middle school students were selected through multistage cluster sampling in 60 primary and middle schools in 6 provinces in China. The questionnaire survey and eyesight test were conducted among all the students selected according to the national student's physique and health survey protocol. Pearson chi-square test and binary multivariate logistic regression analysis were done to identify the influencing factors for myopia in students. RESULTS: The prevalence of myopia among primary and middle school students surveyed was 55.7%, the gender specific difference was statistically significant (59.7% for girls, 51.9% for boys) (P<0.01). The prevalence of myopia increased with age obviously. The prevalence was 35.8% in age group 6-8 years, 58.9% in age group 10-12 years, 73.4% in age group 13-15 years and 81.2% in age group 16-18 years, the differences were statistically significant (P<0.001). Single factor and multivariate analysis showed that parents' myopia, distance between computer screen and eyes, distance less than 30 cm between eyes and book while reading, distance less than 10 cm between chest and the table edge while studying, distance less than 3 cm between fingers and pen tip, sleep time, average outdoor activity time during last week, school sport activities in the afternoon, the size of television set at home, time spent on watching TV and playing computer were the influencing factors for myopia. CONCLUSIONS: The prevalence of myopia is till high in primary and middle school students. Myopia is associated with both genetic factors and individual eye health related behaviors. PMID- 26822640 TI - [Gender specific associations between early puberty and behavioral and emotional characteristics in children]. AB - OBJECTIVE: To understand the gender specific association between early puberty and behavioral and emotional characteristics in children. METHODS: The questionnaire survey was conducted among the girls in grade 2-3, boys in grade 3 4 and both girls and boys in grade 7-8 selected through cluster sampling in 2 middle schools and 2 primary schools in Beijing and Shenyang respectively in November 2014. The questionnaire contents included general information, physical activity and video time, pubertal development scale (PDS) and strength and difficulties questionnaire (SDQ). Descriptive statistics were used to describe the prevalence of early puberty and the detection rate of abnormal behavioral problems. The effects of early puberty on behavioral and emotional problems were estimated with univariate and multivariate logistic regression analyses. The odds ratios and their 95% confidence intervals were calculated. RESULTS: A total of 3253 complete questionnaires were collected, the prevalence of early puberty was 15.9% (518). The detection rate (number) of abnormal emotional symptoms, conduct problems, hyperactivity/inattention, peer relationship problems, pro-social behaviors and total difficulties were 8.3% (269), 9.1% (297), 6.5% (211), 16.4% (534), 9.2% (299) and 13.8% (448) respectively. Multivariate logistic regression analysis showed that early puberty was the risk factor for conduct problems (OR=2.260, 95% CI: 1.322-3.863) and hyperactivity/inattention (OR=1.980, 95% CI: 1.111-3.527) in the girls, and early puberty was risk factor for total difficulties in boys (95%CI: 1.018-2.063). CONCLUSIONS: Early puberty might increase the risk of conduct problems and hyperactivity/inattention in girls and increase the risk of total difficulties in boys. It is important to conduct gender specific psychological intervention among adolescents for improving their physical and mental health. PMID- 26822641 TI - [Relationship between chronic psychosocial stress and BMI among adolescents]. AB - OBJECTIVE: To evaluate the influence of chronic psychosocial stress on BMI in adolescents. METHODS: Physical examination and questionnaire survey were conducted among the students of junior grade 1 and senior grade 1 in 10 middle schools in Xuzhou in September 2011. Their body height and weight were measured at baseline survey and the self-report information about socio-demographic data, emotional symptoms (depressive symptoms, anxiety symptoms), and life style/behavior were collected from them. Chronic psychosocial stress was assessed with Multidimensional Life Events Rating Questionnaire (MLERQ), which consists of five items, stress of family life, school life, peer relation, gender relation and health growth. RESULTS: A total of 5473 valid questionnaires were collected for analysis (2841 from boys and 2632 from girls). The follow-up measurement of body height and weight were conducted in September 2013. A total of 4316 students (2171 boys, 2145 girls) were surveyed, and 1157 students missed the follow up. The psychosocial stress score in the overweight and obese girls at baseline survey was positively associated with BMI-Z increase at follow up survey (P<0.01). No such effect was observed among the boys at follow-up survey. CONCLUSION: High level of chronic psychosocial stress could lead to BMI increase in overweight and obese girls, suggesting that female adolescents are susceptible population of psychosocial stress induced obesity. PMID- 26822642 TI - [Mid-gestational glucose levels and newborn birth weight: birth cohort study]. AB - OBJECTIVE: To understand the association between the blood glucose levels of pregnant women in second trimester detected by 75 gram oral glucose tolerance test (OGTT) and the birth weight of neonates. METHODS: Demographic information collection and OGTT were conducted for 3 081 pregnant women at <=14 gestational weeks and 24-28 gestational weeks respectively. Multiple logistic regression analysis was done to identify the factors associated with the birth weight and the risks of large for gestational age (LGA) in three levels (FPG, OGTT-1 h and OGTT-2 h) of OGTT percentile group, multiple linear regression analysis was used to evaluate the relationships between maternal glucose levels and neonate birth weight. RESULTS: Pre-pregnancy obesity (24.0 kg/m2<=BMI<28.0 kg/m2) (OR=1.4, 95%CI:1.0-2.0, P=0.029) and gestational diabetes mellitus (OR=2.4,95% CI: 1.8 3.2, P<0.001) were the risk factors. Pre-pregnancy underweight (BMI<18.5 kg/m2) (OR=1.6, 95%CI: 1.2-2.2, P=0.003), preeclampsia (OR=4.0, 95%CI: 1.9-8.4, P<0.001) increased the risk for small for gestational age (SGA). Multiple linear regression analysis showed neonate birth weight was positive correlated with maternal glucose levels (beta were 91.99, 33.60, 32.00, respectively, P<0.001). Percentile groups of each OGTT level was linearly positive associated with increased mean value of neonate birth weight, and so with the risk of LGA. CONCLUSIONS: There were positive correlations between maternal glucose levels and neonate birth weight. The risk of LGA increased with the maternal glucose levels, but there was no statistical association between SGA and maternal glucose levels. FPG level is one of the predictors of LGA. Active surveillance and control of maternal glucose level can effectively reduce the risk of LGA. PMID- 26822643 TI - [Epidemiology of injury and risk factors among adults in Guizhou province, 2010]. AB - OBJECTIVE: To understand the epidemiologic characteristics of injury among adults in Guizhou province. METHODS: A questionnaire survey was conducted among 9 280 residents aged >=18 years selected though multistage cluster random sampling in Guizhou to collect the information about their demographic characteristics and incidence data of injury. Logistic regression analysis was done to identify the risk factors. RESULTS: The incidence of injury was 3.5% in the adults surveyed (3.6% in males, 3.4% in females). The incidences of injury in both urban area and rural area were same (3.5%). The incidence of injury was 3.9% in age group 18-44 years, 2.7% in age group 45-59 years, and 3.5% in age group>=60 years, the differences among different age groups were statistically significant (chi2=7.949, P=0.019). The top three injury causes were fall (35.0%), road traffic accident (20.0%) and animal bite (19.2%). The top three injury causes in the elderly were fall (59.3%), animal bite (22.0%) and sharp instrument cut (10.2%). Among the elderly, the incidence of road traffic injury was higher in males (1.1%) than in females (0.3%), the difference was statistically significant (chi2=18.156, P=0.000). The incidence of fall in urban area (1.6%) was higher than that in rural area (1.1%), the difference was statistically significant (chi2=4.616, P=0.032). Drinking and drunk driving, fatigue driving, smoking and gender were the influencing factors for injury. CONCLUSION: Injury related high risk behaviors were common in adults in Guizhou, it is necessary to develop effective intervention measures to prevent injury. PMID- 26822644 TI - [Distribution of both HBsAg and HBsAb negative adults in Mianyang, Sichuan province]. AB - OBJECTIVE: To understand the distribution of both HBsAg and HBsAb negative adults in Mianyang, Sichuan province, and provide evidences for the development of adult immunization policy. METHODS: From June 2013 to April 2014, a total of 200 929 people aged >=15 years were selected in Mianyang through stratified cluster random sampling to conduct an interview with standard questionnaire. The blood samples were collected from them for the detection of HBsAg and HBsAb with enzyme linked immunosorbent assay (ELISA). RESULTS: Among the people surveyed, 13 903 were HBsAg positive (7.0%), 93 763 were HBsAb positive (46.6%), and 93 122 were both HBsAg and HBsAb negative (46.3%). The negative rate of both HBsAg and HBsAb in females (47.1%) was higher than that in males (45.4%). The negative rate of both HBsAg and HBsAb increased with age. The negative rate of both HBsAg and HBsAb was highest in people aged >=65 years (50.3%) and lowest in people aged 15 24 years (42.9%). The negative rate of both HBsAg and HBsAb was highest in farmers (51.1%) and lowest in medical workers (24.1%). The negative rate of both HBsAg and HBsAb was highest in the widowed (51.1%) and lowest in the unmarried (41.6%). The negative rate of both HBsAg and HBsAb was lower in people with family history of hepatitis B (36.5%) than in people without family history of hepatitis B (46.6%). The negative rate of both HBsAg and HBsAb in Han ethnic group was lower (46.3%) than that in Qiang ethnic group (53.1%), but higher than that in other ethnic groups (43.9%). The negative rate of both HBsAg and HBsAb was higher in rural area (48.9%) than in urban area (43.0%). The negative rate of both HBsAg and HBsAb was lower in people who had received hepatitis B immunization (43.7%) than in people who had received no hepatitis B immunization (47.3%). The differences were all statistical significant (P<0.01). CONCLUSION: The negative rate of both HBsAg and HBsAb was 46.3% in people aged >=15 years in Mianyang. General population are susceptible to hepatitis B virus infection. It is necessary to develop and implement appropriate hepatitis B immunization strategy for local adult population. PMID- 26822645 TI - [Long-term efficacy of neonatal hepatitis B vaccination against chronic hepatitis B virus infection and chronic liver disease: a cross-sectional study based on Qidong Hepatitis B Intervention Study]. AB - OBJECTIVE: To evaluate the long-term protection efficacy of neonatal hepatitis B vaccination on chronic hepatitis B (CHB) and liver fibrosis and cirrhosis in adults. METHODS: From January to October, 2013, a cross-sectional study was conducted among the participants from Qidong Hepatitis B Intervention Study (QHBIS), who were selected through stratified random sampling. The detections of serum alanine aminotransferase (ALT), HBsAg, anti-HBs, anti-HBc, HBeAg, and anti HBe were conducted and ultrasonography on liver, gallbladder and spleen was performed for them. The positive rates of each serologic markers, the prevalence of active CHB and liver fibrosis and cirrhosis were calculated, the gender specific differences between vaccination group and control group were compared with Chi-square test. RESULTS: A total of 4 421 participants aged (25.59+/-1.84) years in vaccination group and 3 880 participants aged (26.61+/-2.24) years in control group were surveyed. The positive rates of HBsAg, anti-HBs, anti-HBc, HBeAg and anti-HBe were 2.38%, 37.73%, 3.78%, 0.57% and 2.15% in vaccination group, and 9.02%, 29.41%, 16.83%, 2.73% and 8.87% in control group, respectively, the differences between two groups were statistically significant (all P<0.05). The prevalence of active CHB and liver fibrosis and cirrhosis were 0.45% and 0.16% in vaccination group, 1.29% and 0.39% in control group, the differences between two groups were statistically significant (P<0.05). The active CHB prevalence was lower in females than in males in both vaccination group and control group (P<0.05). The liver fibrosis and cirrhosis prevalence was lower in females than in males in control group (P<0.05); whereas, no statistical significant difference in liver fibrosis & cirrhosis prevalence between males and females was found in vaccination group (P>0.05). CONCLUSIONS: Protection conferred by neonatal hepatitis B vaccination could last to marrying age. The gender specific difference in protection efficacy needs further study. PMID- 26822646 TI - [Factors influencing access to methadone maintenance treatment among injecting drug users attending antiretroviral treatment clinics in two counties, Yunnan province]. AB - OBJECTIVE: To understand the demographic characteristics of HIV infected injecting drug users (IDUs) with access to antiretroviral therapy (ART) and to identify the factors influencing their access to methadone maintenance treatment (MMT). METHODS: Outpatients infected with HIV through injecting drug use were selected from the ART clinics in 2 counties in Yunnan province. They were divided into 2 groups, MMT group and non MMT group. Descriptive epidemiologic analysis was conducted on their demographic characteristics, disease history and high risk behaviors and logistic regression analysis was done to identify the factors associated with the access to MMT. RESULTS: Among 635 IDUs (536 males, 99 females) surveyed, 247 received MMT (38.9%), 388 received no MMT(61.1%). The median age was 40.33 years and the median diagnosed HIV infection time was 6.08 years. Multivariate logistic regression indicated that being female (OR=2.40, 95%CI:1.00-5.74), educational level of junior high school (OR=3.28, 95%CI:1.75 6.14), educational level of senior high school or above (OR=7.10, 95%CI:1.90 26.62), more than 6 years of diagnosed HIV infection history (OR=3.84, 95% CI:2.11-6.98) and HCV positive (OR=6.21, 95% CI:3.06-12.58) were the positive factors influencing IDUs' access to MMT. However, being married (OR=0.38, 95%CI:0.20-0.72) or being employed (OR=0.01, 95%CI:0.00-0.02) were the negative factors influencing IDUs' access to MMT. CONCLUSION: The proportion of HIV infected IDUs who received MMT in ART clinics was still very low in the two counties, targeted intervention measures should be taken to increase the MMT coverage, especially among those who are married or employed. PMID- 26822647 TI - [Analysis on accuracy and influencing factors of oral fluid-based rapid HIV self testing among men who have sex with men]. AB - OBJECTIVE: To understood the accuracy of oral fluid-based rapid HIV self-testing among men who have sex with men (MSM) and related factors. METHODS: Survey was conducted among MSM selected through non-probability sampling to evaluate the quality of their rapid HIV self-testing, and related information was analyzed. RESULTS: The most MSM were aged 21-30 years (57.0%). Among them, 45.7% had educational level of college or above, 78.5% were unmarried, 59.3% were casual laborers. The overall accuracy rate of oral fluid based self-testing was 95.0%, the handling of"inserting test paper into tube as indicated by arrow on it"had the highest accuracy rate (98.0%), and the handling of"gently upsetting tube for 3 times"had lowest accuracy rate (65.0%); Chi-square analysis showed that educational level, no touch with middle part of test paper, whether reading the instruction carefully, whether understanding the instruction and inserting test paper into tube as indicated by the arrow on it were associated with the accuracy of oral fluid-based rapid HIV self-testing, (P<0.05). Multivariate logistic regression analysis indicated that educational level, no touch with middle part of test paper and understanding instructions were associated with the accuracy of oral fluid-based rapid HIV self-testing. CONCLUSIONS: The accuracy of oral fluid based rapid HIV self-testing was high among MSM, the accuracy varied with the educational level of the MSM. Touch with the middle part of test paper or not and understanding the instructions or not might influence the accuracy of the self testing. PMID- 26822648 TI - [Gender characteristics and HIV/AIDS related knowledge awareness and behaviors of transgender women]. AB - OBJECTIVE: To understand the gender characteristics, HIV/AIDS related knowledge awareness and behaviors of transgender women. METHODS: A questionnaire survey was conducted among the transgender women recruited through snowball sampling in Jinan in 2014, and descriptive epidemiologic analysis was conducted on the survey results. RESULTS: A total of 55 transgender women were surveyed, all of them were male physically and female psychologically. Serious gender conflict occurred in 27 subjects (49.1%), and very serious gender conflict occurred in 8 subjects (14.5%). Thirty subjects dressed up as a man in social life, accounting for 54.5%; 25 subjects dressed up as a women in social life, accounting for 45.5%. The average awareness rate of HIV/AIDS related knowledge was 57.9%(22/38). The awareness of knowledge about AIDS associated behaviors, such as multi sex partner and anal sex, was poor. For the lovers or sexual partners, 58.2% of the subjects (32/55) would choose males and 50.9% of the subjects (28/55) had chosen males, and for the sex partner at latest sex, 63.6%(35/55) of the subjects had chosen males. Up to 56.3% of the subjects had sex with casual sexual partners (net friends and partners of one-night stand) at latest sex behavior. Among the subjects surveyed, 18(32.7%) never used condoms; 29(52.7%) used condoms occasionally; 4(7.3%) used condoms frequently and 4(7.3%) used condoms at each sex. CONCLUSIONS: AIDS associated high risk behaviors were common among the transgender women, such as unprotected anal sex, multiple sexual partners, frequent sex and poor condom use. It is necessary to conduct the study of the HIV infection prevention in transgender women. PMID- 26822649 TI - [Spatial data based study of distribution of hepatitis C in Chongqing]. AB - OBJECTIVE: To understand the spatial distribution of hepatitis C in Chongqing and its influencing factors. METHODS: The surveillance data of hepatitis C in 38 counties in Chongqing from January 2010 to December 2014 were collected, and spatial autocorrelation analysis and spatial regression analysis were conducted respectively by using software GeoDa 1.6.7. RESULTS: The reported incidence of hepatitis C in Chongqing ranged from 7.3/100,000 to 13.6/100,000 during 2010 2014, with the annual reported incidence of 10.3/100,000. The global Moran's I values were 0.478, 0.503, 0.529, 0.438, 0.406 respectively (P<0.05). The local spatial autocorrelation analysis indicated there were 6, 4, 7, 5 and 6 areas with high incidences of hepatitis C in 2010, 2011, 2012, 2013 and 2014 respectively. Spatial regression analysis revealed that the reported incidence of hepatitis C in Chongqing was associated with the urbanization rate (Z=2.126, P=0.033). CONCLUSIONS: The spatial distribution of hepatitis C in Chongqing from 2010 to 2014 was highly clustered. The hot spot of hepatitis C were mainly in the core areas and extended areas with well-developed economy, however the cold spot were in southeastern ecological reserve area with less developed economy. Urbanization had a certain positive influence on the distribution of hepatitis C in Chongqing. PMID- 26822650 TI - [Spatial-temporal distribution of hepatitis B in Gansu province, 2009-2014]. AB - OBJECTIVE: To understand the hot/cold spots and the spatial-temporal clustering of hepatitis B in Gansu province during 2009-2014 by using spatial statistics, and provide scientific evidence for the prevention and control of hepatitis B. METHODS: The spatial hot/cold spots and its trend, and the time frame and areas of its spatial-temporal clustering of hepatitis B in Gansu were analyzed by using the county specific incidence of hepatitis B from 2009 to 2014 and spatial statistical software GeoDa and SatScan. RESULTS: The incidences of hepatitis B from 2009 to 2014 in Gansu were spatial autocorrelated respectively. Local G scan statistics indicated that the number of hot spots was in decline in Hexi area, while the hot spots was in increase in Linxia Hui autonomous prefecture and Gannan Tibetan autonomous prefecture. There was no obvious pattern in cold spots. Temporal-spatial scan statistics showed that the areas with high hepatitis B incidence most likely clustered in Hexi area during 2009-2011, and the areas with low hepatitis B incidence most likely clustered in eastern Gansu during 2012 2014. CONCLUSIONS: The spatial and temporal clustering of hepatitis B was observed in Gansu from 2009 to 2014. The number of hot spots in Hexi area was in decline, while the numbers of hot spots in Linxia and Gannan were in increase, suggesting that the hepatitis B control and prevention in these areas should be strengthened. PMID- 26822651 TI - [Misreporting rate and influencing factors regarding the routes of transmission among reported HIV patients in Yili Kazakh Autonomous Prefecture of Xinjiang Uygur Autonomous Region of China]. AB - OBJECTIVE: To understand the misreporting rate regarding the routes of transmission among the reported HIV patients in Yili prefecture of Xinjiang, since 2011. METHODS: An investigation focusing on the route of transmission among people living with HIV/AIDS was carried out to clarify the responsible reasons for the situation. RESULTS: The overall incorrect reporting rate on the route of transmission was 10.8%.The proportion of heterosexual transmission route was over estimated by 63.8% to 72.0%. However, the proportion of injecting drug was underestimated by 27.5% to 22.2%. The number of cases being confirmed as through heterosexual transmission but incorrectly reported was quite high, contributing 82.6% of all the incorrectly reported cases. Most of the patients that incorrect reported, were moved from injecting drug use to heterosexual transmission, which contributed 79.5% of all the total incorrectly reported cases. Results from multi factor analysis showed that the risk related to incorrect reporting was 3.64 times in males than in females. People who anticipated to receive HIV testing were 2.23 times more than those who had not. Old-age groups were 3.511, 4.053, 4.415 and 6.524 times higher than those people who were aged below 16 years. CONCLUSIONS: The proportion of heterosexual transmission route was over- estimated while the proportion on injecting drug use was underestimated. However, the transmission pattern had changed from injecting drug use at the early epidemic stage, to current sexual transmission mode. We recommended that more attentions should be paid to patients who were males, at older age or those who had no expectation in receiving the HIV testing, during the initial following-up stage. PMID- 26822652 TI - [Prediction of potential geographic distribution of Lyme disease in Qinghai province with Maximum Entropy model]. AB - OBJECTIVE: To predict the potential geographic distribution of Lyme disease in Qinghai by using Maximum Entropy model (MaxEnt). METHODS: The sero-diagnosis data of Lyme disease in 6 counties (Huzhu, Zeku, Tongde, Datong, Qilian and Xunhua) and the environmental and anthropogenic data including altitude, human footprint, normalized difference vegetation index (NDVI) and temperature in Qinghai province since 1990 were collected. By using the data of Huzhu Zeku and Tongde, the prediction of potential distribution of Lyme disease in Qinghai was conducted with MaxEnt. The prediction results were compared with the human sero-prevalence of Lyme disease in Datong, Qilian and Xunhua counties in Qinghai. RESULTS: Three hot spots of Lyme disease were predicted in Qinghai, which were all in the east forest areas. Furthermore, the NDVI showed the most important role in the model prediction, followed by human footprint. Datong, Qilian and Xunhua counties were all in eastern Qinghai. Xunhua was in hot spot areaII, Datong was close to the north of hot spot area III, while Qilian with lowest sero-prevalence of Lyme disease was not in the hot spot areas. The data were well modeled in MaxEnt (Area Under Curve=0.980). CONCLUSIONS: The actual distribution of Lyme disease in Qinghai was in consistent with the results of the model prediction. MaxEnt could be used in predicting the potential distribution patterns of Lyme disease. The distribution of vegetation and the range and intensity of human activity might be related with Lyme disease distribution. PMID- 26822653 TI - [Disability adjusted life years of type 2 diabetes in population in Zhejiang province, 2013]. AB - OBJECTIVE: To estimate the disease burden of type 2 diabetes in population in Zhejiang in 2013. METHODS: According to the method in global burden of disease study (GBD) 2010, the related disability adjusted life years (DALYs), years of life lost (YLL) and years lived with disability (YLD) were calculated by using the incidence, prevalence and mortality data of type 2 diabetes in population in Zhejiang and DISMODII. RESULTS: The overall DALYs of type 2 diabetes was 5.36 per 1000 population, which was higher in women (5.49 per 1000) than in men (5.24 per 1000), The population in urban area had higher DALYs (5.47 per 1000) than those in rural area (5.42 per 1000). The DALYs in old population was high, which peaked in age group 80-84 years (32.63 per 1000) with YLL/YLD of 0.62. The disease burden of type 2 diabetes was mainly caused by disability. CONCLUSION: The YLL of type 2 diabetes in Zhejiang was higher than the national average level. PMID- 26822654 TI - [Estimation of excess numbers of viral diarrheal cases among children aged <5 years in Beijing with adjusted Serfling regression model]. AB - OBJECTIVE: To estimate the excess numbers of viral diarrheal cases among children aged <5 years in Beijing from 1 January 2011 to 23 May 2015. METHODS: The excess numbers of diarrheal cases among the children aged <5 years were estimated by using weekly outpatient visit data from two children's hospital in Beijing and adjusted Serfling regression model. RESULTS: The incidence peaks of viral diarrhea were during 8th-10th week and 40th-42nd week in 2011, 40th-46th week in 2012, 43rd-49th week in 2013 and 45th week in 2014 to 11th week in 2015 respectively. The excess numbers of viral diarrheal cases among children aged <5 years in the two children's hospital were 911(95%CI: 261-1 561), 1 998(95%CI: 1 250-2 746), 1 645 (95%CI: 891-2 397), 2 806(95%CI: 1 938-3 674) and 1 822(95%CI: 614-3 031) respectively, accounting for 40.38%(95%CI: 11.57%-69.19%), 44.21% (95% CI: 27.66%-60.77%), 45.08% (95% CI: 24.42%-65.69%), 60.87% (95% CI: 42.04% 79.70%) and 66.62% (95% CI: 22.45%-110.82%) of total outpatient visits due to diarrhea during 2011-2015, respectively. Totally, the excess number of viral diarrheal cases among children aged <5 years in Beijing was estimated to be 18 731(95%CI: 10 106-27 354) from 2011 to 23 May 2015. CONCLUSIONS: Winter is the season of viral diarrhea for children aged <5 years. The adjusted Serfling regression model analysis suggested that close attention should be paid to the etiologic variation of viruses causing acute gastroenteritis, especially the etiologic variation of norovirus. PMID- 26822655 TI - [Incidence trend of malignant tumors in children in Shanghai]. AB - OBJECTIVE: To understand the incidence trend of malignant tumors in children aged <15 years in Shanghai. METHODS: The <15 years old children diagnosed with cancer in Shanghai between 2009 and 2011 were included in this study. The types of malignant tumors were classified according to International Classification of Childhood Cancer, Version 3 (ICCC-3). The gender and age specific incidences of malignant tumors were analyzed. Software Joinpoint was used to calculate the annual percentage of childhood cancer cases. RESULTS: A total of 460 cases of childhood cancer were diagnosed in Shanghai during 2009-2011, accounting for 0.3% of total cancer cases. The crude incidence was 129.0 per million and the age standardized rate (ASR) was 129.6 per million. The ASR was higher in boys (142.1 per million) than in girls (116.4 per million). The boy to girl ratio was 1.2(95%CI: 1.0-1.5). The incidence was highest in age group <5 years (165.1 per million). The incidences in age groups 5-9 years and 10-14 years were 101.2 per million and 113.9 per million, respectively. Leukemia was the most common cancer in children (n=165, 35.9%, ASR: 47.0 per million), followed by central nervous system tumors (n=91, 19.8%, ASR: 25.6 per million) and lymphomas (n=45, 9.8%, ASR: 12.6 per million). The age and gender specific incidence of malignant tumors and the type specific incidence of malignant tumors in children in Shanghai had no significant changes during the study period. CONCLUSIONS: The incidence of malignant tumors was higher in boys than in girls in Shanghai. Leukemia, central nervous system tumors and lymphomas were the three most common cancers in children. The overall incidence of malignant tumors in children in Shanghai had no significant changes during 2002-2011. PMID- 26822656 TI - [Characteristics of drug resistance and molecular type of Salmonella typhi and Salmonella paratyphi isolated in Henan province, 2009-2011]. AB - OBJECTIVE: To investigate the antibiotic resistance and pulsed field gel electrophoresis (PFGE) patterns of clinical isolates of Salmonella (S.) typhi and S. paratyphi in Henan province during 2009-2011. METHODS: According to molecular typing and Salmonella K-B drug susceptibility test method published by international PulseNet bacterial infectious disease monitoring network and USA Clinical and Laboratory Standards Institute (CLSI), the drug susceptibility and PFGE molecule characteristics of 78 S. typhi and S. paratyphi strains isolated from sentinel hospitals in Henan were analyzed. RESULTS: The 78 strains of S. typhi and S. paratyphi were resistant to 13 kinds of antibiotics, in which 62 were multidrug resistant (79.5%), 4 were resistant to 2-3 kinds of antibiotics (5.1%), 41 were resistant to 5-8 kinds of antibiotics (52.6%), 14 were resistant to 9-10 kinds of antibiotics (17.9%), 3 were resistant to 11-12 kinds of antibiotics (3.8%). The resistant rate to cephalosporins, quinolones and other 3 kinds of antibiotic showed an increase trends. Seventy two strains of S. typhi and S. paratyphi could be divided 14 molecular patterns by digestion with XbaI and PFGE, each pattern contains 1-47 strains which shared the similarity of 66.03%-100.00%. CONCLUSIONS: The drug resistance of clinical isolates of S. typhi and S. paratyphi was serious in Henan. The PFGE patterns showed diversity, but the predominant patterns could be still found. The PFGE patterns of some strains were associated with their drug resistance. PMID- 26822657 TI - [Epidemiologic and etiologic characteristics of diarrheagenic Escherichia coli infection in population in Shenzhen]. AB - OBJECTIVE: To understand the epidemiologic and etiologic characteristics of diarrheagenic Escherichia (E.) coli infections in Shenzhen. METHODS: Stool samples were collected from acute diarrheal patients in four sentinel hospitals in Shenzhen and diarrheagenic E. coli strains were isolated and identified with multiplex real-time PCR. Serotyping and pulsed-field gel electrophoresis (PFGE) typing were conducted for the diarrheagenic E. coli isolates. RESULTS: A total of 74 diarrheagenic E. coli strains were isolated from 1 823 stool samples (4.06%). The patients were mainly young children aged <3 years and adults aged 20-39 years, and the infections mainly occurred during May-September of a year. Enterotoxigenic E. coli (ETEC) and enteropathognic E. coli (EPEC) were predominant (45.9% and 31.1%). Serogroups and PFGE patterns varied among the diarrheagenic E. coli isolates. However, serogroup O159 were predominant in ETEC and there were 5 clusters with >=2 strains sharing same PFGE patterns. CONCLUSIONS: ETEC and EPEC were predominant in diarrheagenic E. coli strains isolated from diarrheal patients in Shenzhen. Age and season specific characteristics of diarrheagenic E. coli infections were observed. The serotypes and PFGE patterns of diarrheagenic E. coli strains varied. Close attention should be paid to the possible ETEC outbreak. PMID- 26822658 TI - [Prevalence of chronic obstructive pulmonary disease among community population aged >=40 in China: a Meta-analysis on studies published between 1990 and 2014]. AB - OBJECTIVE: To understand the prevalence of chronic obstructive pulmonary disease (COPD) among the community population aged >=40 years in China from 1990 to 2014. METHODS: The studies on the prevalence of COPD among the community population in China published from 1990 to 2014 were retrieved from the following databases: Chinese BioMedical Literature Database (CBM), Chinese Journal Full-text Database (CNKI), Wanfang Database, PubMed and EBSCO. Mantel-Haenszel fixed effect and random effect model and software Stata were used for statistical analysis. RESULTS: A total 30 studies were included in the Meta analysis. The pooled prevalence of COPD was 9.9%(95%CI: 8.8%-11.0%). The prevalence was higher in males (13.0%, 95%CI: 11.5%-14.4%) than in females (5.8%, 95% CI: 4.9%-6.6%), and the prevalence of COPD increased with age obviously from 3.2% in age group 40-49 years (95%CI: 2.5%-3.9%) to 20.3% in age group >=70 years (95%CI: 18.2%-22.4%). The differences in prevalence among different areas had no statistical significance. CONCLUSIONS: The prevalence of COPD in population aged >=40 years increased gradually in China in recent 20 years. Obvious heterogeneity was found among the results of the studies due to the different diagnostic standards and sample sizes. PMID- 26822659 TI - [Biology and culture: a dimension of collaboration between anthropology and epidemiology]. AB - Biology is the important basis of epidemiological study. Based on biology, psychology, social and cultural factors can influence human's health and disease incidence. The medical mode has changed from "biomedical mode" to "bio-psycho social medical model" , but culture factor was neglected somewhat during this process, so paying attention to culture factor in anthropologic study and using it as biologic basis in epidemiologic study might be a dimension of collaboration between of anthropology and epidemiology. PMID- 26822660 TI - [The benefit of multi-disciplines combination in evidence-based medicine teaching practice]. AB - In this article, we gave a detail description on the experience of teaching evidence-based medicine (EBM) in undergraduate students and graduate students as well as for continue medical education. The staff of Department of EBM was from variety of sub-discipline, including epidemiologists, physicians, surgeons and librarian. To make the course smoothly, the member of the department discussed the plan together frequently, and had conduct test lecture, which make the course to become perfect. The key for the development in our department is powerful organization and leadership, pursuing perfect, keeping with the progress of the EBM and team-working. PMID- 26822661 TI - [Progress in research of reasons for women engaging in commercial sex]. AB - With the development of economy, increase of cultural exchanges and changes of people's ideology in China, the number of female sex workers (FSWs) increased rapidly under the influence of various social factors. The diverse motivations for women engaging in commercial sex have been observed. Foreign researchers have conducted some surveys of factors associated with female commercial sex, while few such studies were conducted among FSWs in China. This paper summarizes the progress in the research of reasons for women engaging in commercial sex both at home and abroad to provide evidence for future study. PMID- 26822662 TI - New alpha-glucosidase inhibitors from marine algae-derived Streptomyces sp. OUCMDZ-3434. AB - Wailupemycins H (1) and I (2) with a new skeleton coupled two 6-(2 phenylnaphthalene-1-yl)pyrane-2-one nuclei to a -CH2- linkage were identified from the culture of Streptomyces sp. OUCMDZ-3434 associated with the marine algae, Enteromorpha prolifera. Compounds 1 and 2 are two new alpha-glucosidase inhibitors with the Ki/IC50 values of 16.8/19.7 and 6.0/8.3 MUM, respectively. In addition, the absolute configurations of wailupemycins D (3) and E (4) are also resolved in this paper for the first time. PMID- 26822663 TI - High rectal tumor resection using single-incision laparoscopic approach (with video). PMID- 26822664 TI - Reconstruction of the inferior vena cava due to blunt hepatic trauma. PMID- 26822665 TI - Proctologic surgery done by residents - Complications preprogrammed? AB - INTRODUCTION: In current literature, the participation of residents in surgical procedures is discussed as a negative outcome factor, particularly due to an increase of postoperative complications. This study investigated whether minor proctologic surgery with resident participation has a higher rate of postoperative complications. PATIENTS AND METHODS: All patients who underwent an elective Milligan-Morgan hemorrhoidectomy or a resection of pilonidal sinus with rotational flap closure between January 2007 and December 2013 where included in a retrospective database. Primary outcome measure was postoperative complications rate with and without resident participation. RESULTS: Forty-two (6 females: 36 males) patients underwent resection of pilonidal sinus and 61 (17 females: 44 males) patients received a hemorrhoidectomy. Twenty-two patients with pilonidal sinus and 26 patients with hemorrhoids were operated by residents. There were no differences in patient demographics. Residents need significantly more time to perform a pilonidal sinus resection (54min vs. 34.5min; P = 0.004). For hemorrhoidectomy, there were no significant differences in operative time (24min vs. 23.5min; P = 0.656). There were no significant differences in the resident and the consultant group, neither in hemorrhoidectomy nor in pilonidal sinus resection regarding readmission or outpatient visits. In the group of patients with pilonidal sinus resections, 3 patients developed a recurrence, leading to a recurrence rate of 7.1% without significant differences between the two groups (0 vs. 3; P = 0.09). CONCLUSION: The participation of residents in proctologic procedures is not associated with higher postoperative complication rates. Residents should be exposed to proctology procedures on a regular basis, even though the operative time will be prolonged. PMID- 26822666 TI - HelexKids: A word frequency database for Greek and Cypriot primary school children. AB - In this article, we introduce HelexKids, an online written-word database for Greek-speaking children in primary education (Grades 1 to 6). The database is organized on a grade-by-grade basis, and on a cumulative basis by combining Grade 1 with Grades 2 to 6. It provides values for Zipf, frequency per million, dispersion, estimated word frequency per million, standard word frequency, contextual diversity, orthographic Levenshtein distance, and lemma frequency. These values are derived from 116 textbooks used in primary education in Greece and Cyprus, producing a total of 68,692 different word types. HelexKids was developed to assist researchers in studying language development, educators in selecting age-appropriate items for teaching, as well as writers and authors of educational books for Greek/Cypriot children. The database is open access and can be searched online at www.helexkids.org . PMID- 26822667 TI - Descriptive norms for 350 Chinese idioms with seven syntactic structures. AB - The most important forms of idioms in Chinese, chengyus (CYs), have a fixed length of four Chinese characters. Most CYs are joined structures of two, two character words-subject-verb units (SVs), verb-object units (VOs), structures of modification (SMs), or verb-verb units-or of four, one-character words. Both the first and second pairs of words in a four-word CY form an SV, a VO, or an SM. In the present study, normative measures were obtained for knowledge, familiarity, subjective frequency, age of acquisition, predictability, literality, and compositionality for 350 CYs, and the influences of the CYs' syntactic structures on the descriptive norms were analyzed. Consistent with previous studies, all of the norms yielded a high reliability, and there were strong correlations between knowledge, familiarity, subjective frequency, and age of acquisition, and between familiarity and predictability. Unlike in previous studies (e.g., Libben & Titone in Memory & Cognition, 36, 1103-1121, 2008), however, we observed a strong correlation between literality and compositionality. In general, the results seem to support a hybrid view of idiom representation and comprehension. According to the evaluation scores, we further concluded that CYs consisting of just one SM are less likely to be decomposable than those with a VOVO composition, and also less likely to be recognized through their constituent words, or to be familiar to, known by, or encountered by users. CYs with an SMSM composition are less likely than VOVO CYs to be decomposable or to be known or encountered by users. Experimental studies should investigate how a CY's syntactic structure influences its representation and comprehension. PMID- 26822668 TI - The Glasgow Voice Memory Test: Assessing the ability to memorize and recognize unfamiliar voices. AB - One thousand one hundred and twenty subjects as well as a developmental phonagnosic subject (KH) along with age-matched controls performed the Glasgow Voice Memory Test, which assesses the ability to encode and immediately recognize, through an old/new judgment, both unfamiliar voices (delivered as vowels, making language requirements minimal) and bell sounds. The inclusion of non-vocal stimuli allows the detection of significant dissociations between the two categories (vocal vs. non-vocal stimuli). The distributions of accuracy and sensitivity scores (d') reflected a wide range of individual differences in voice recognition performance in the population. As expected, KH showed a dissociation between the recognition of voices and bell sounds, her performance being significantly poorer than matched controls for voices but not for bells. By providing normative data of a large sample and by testing a developmental phonagnosic subject, we demonstrated that the Glasgow Voice Memory Test, available online and accessible from all over the world, can be a valid screening tool (~5 min) for a preliminary detection of potential cases of phonagnosia and of "super recognizers" for voices. PMID- 26822669 TI - Recall and response time norms for English-Swahili word pairs and facts about Kenya. AB - In the vast literature exploring learning, many studies have used paired associate stimuli, despite the fact that real-world learning involves many different types of information. One of the most popular materials used in studies of learning has been a set of Swahili-English word pairs for which Nelson and Dunlosky (Memory 2; 325-335, 1994) published recall norms two decades ago. These norms involved use of the Swahili words as cues to facilitate recall of the English translation. It is unclear whether cueing in the opposite direction (from English to Swahili) would lead to symmetric recall performance. Bilingual research has suggested that translation in these two different directions involves asymmetric links that may differentially impact recall performance, depending on which language is used as the cue (Kroll & Stewart, Journal of Memory and Language 33; 149-174,1994). Moreover, the norms for these and many other learning stimuli have typically been gathered from college students. In the present study, we report recall accuracy and response time norms for Swahili words when they are cued by their English translations. We also report norms for a companion set of fact stimuli that may be used along with the Swahili-English word pairs to assess learning on a broader scale across different stimulus materials. Data were collected using Amazon's Mechanical Turk to establish a sample that was diverse in both age and ethnicity. These different, but related, stimulus sets will be applicable to studies of learning, metacognition, and memory in diverse samples. PMID- 26822670 TI - A Bayesian approach for estimating the probability of trigger failures in the stop-signal paradigm. AB - Response inhibition is frequently investigated using the stop-signal paradigm, where participants perform a two-choice response time task that is occasionally interrupted by a stop signal instructing them to withhold their response. Stop signal performance is formalized as a race between a go and a stop process. If the go process wins, the response is executed; if the stop process wins, the response is inhibited. Successful inhibition requires fast stop responses and a high probability of triggering the stop process. Existing methods allow for the estimation of the latency of the stop response, but are unable to identify deficiencies in triggering the stop process. We introduce a Bayesian model that addresses this limitation and enables researchers to simultaneously estimate the probability of trigger failures and the entire distribution of stopping latencies. We demonstrate that trigger failures are clearly present in two previous studies, and that ignoring them distorts estimates of stopping latencies. The parameter estimation routine is implemented in the BEESTS software (Matzke et al., Front. Quantitative Psych. Measurement, 4, 918; 2013a) and is available at http://dora.erbe-matzke.com/software.html . PMID- 26822671 TI - Confidence intervals for correlations when data are not normal. AB - With nonnormal data, the typical confidence interval of the correlation (Fisher z') may be inaccurate. The literature has been unclear as to which of several alternative methods should be used instead, and how extreme a violation of normality is needed to justify an alternative. Through Monte Carlo simulation, 11 confidence interval methods were compared, including Fisher z', two Spearman rank order methods, the Box-Cox transformation, rank-based inverse normal (RIN) transformation, and various bootstrap methods. Nonnormality often distorted the Fisher z' confidence interval-for example, leading to a 95 % confidence interval that had actual coverage as low as 68 %. Increasing the sample size sometimes worsened this problem. Inaccurate Fisher z' intervals could be predicted by a sample kurtosis of at least 2, an absolute sample skewness of at least 1, or significant violations of normality hypothesis tests. Only the Spearman rank order and RIN transformation methods were universally robust to nonnormality. Among the bootstrap methods, an observed imposed bootstrap came closest to accurate coverage, though it often resulted in an overly long interval. The results suggest that sample nonnormality can justify avoidance of the Fisher z' interval in favor of a more robust alternative. R code for the relevant methods is provided in supplementary materials. PMID- 26822673 TI - A General Strategy for the Nickel-Catalyzed C-H Alkylation of Anilines. AB - The C-H alkylation of aniline derivatives with both primary and secondary alkyl halides was achieved with a versatile nickel catalyst of a vicinal diamine ligand. Step-economic access to functionalized 2-pyrimidyl anilines, key structural motifs in anticancer drugs, is thus provided. The C-H functionalization proceeded through facile C-H activation and SET-type C-X bond cleavage with the assistance of a monodentate directing group, which could be removed in a traceless fashion. PMID- 26822672 TI - Precisely parameterized experimental and computational models of tissue organization. AB - Patterns of cellular organization in diverse tissues frequently display a complex geometry and topology tightly related to the tissue function. Progressive disorganization of tissue morphology can lead to pathologic remodeling, necessitating the development of experimental and theoretical methods of analysis of the tolerance of normal tissue function to structural alterations. A systematic way to investigate the relationship of diverse cell organization to tissue function is to engineer two-dimensional cell monolayers replicating key aspects of the in vivo tissue architecture. However, it is still not clear how this can be accomplished on a tissue level scale in a parameterized fashion, allowing for a mathematically precise definition of the model tissue organization and properties down to a cellular scale with a parameter dependent gradual change in model tissue organization. Here, we describe and use a method of designing precisely parameterized, geometrically complex patterns that are then used to control cell alignment and communication of model tissues. We demonstrate direct application of this method to guiding the growth of cardiac cell cultures and developing mathematical models of cell function that correspond to the underlying experimental patterns. Several anisotropic patterned cultures spanning a broad range of multicellular organization, mimicking the cardiac tissue organization of different regions of the heart, were found to be similar to each other and to isotropic cell monolayers in terms of local cell-cell interactions, reflected in similar confluency, morphology and connexin-43 expression. However, in agreement with the model predictions, different anisotropic patterns of cell organization, paralleling in vivo alterations of cardiac tissue morphology, resulted in variable and novel functional responses with important implications for the initiation and maintenance of cardiac arrhythmias. We conclude that variations of tissue geometry and topology can dramatically affect cardiac tissue function even if the constituent cells are themselves similar, and that the proposed method can provide a general strategy to experimentally and computationally investigate when such variation can lead to impaired tissue function. PMID- 26822674 TI - Managing patients taking novel oral anticoagulants (NOAs) in dentistry: a discussion paper on clinical implications. AB - BACKGROUND: The aim of this paper is to contribute to the discussion on how to approach patients taking new orally administered anticoagulants (NOAs) dabigatran etexilate (a direct thrombin inhibitor), rivaroxaban and apixaban (factor Xa inhibitors), before, during and after dental treatment in light of the more recent knowledges. DISCUSSION: In dentistry and oral surgery, the major concerns in treatment of patients taking direct thrombin inhibitors and factor Xa inhibitors is the risk of haemorrhage and the absence of a specific reversal agent. The degree of renal function, the complexity of the surgical procedure and the patient's risk of bleeding due to other concomitant causes, are the most important factors to consider during surgical dental treatment of patients taking NOAs. For patients requiring simple dental extraction or minor oral surgery procedures, interruption of NOA is not generally necessary, while an higher control of bleeding and discontinuation of the drug (at least 24 h) should be requested before invasive surgical procedures, depending on renal functionality. The clinician has to consider that the number of patients taking NOAs is rapidly increasing. Since available data are not sufficient to establish an evidence based dental management, the dentist must use caution and attention when treating patients taking dabigatran, rivaroxaban and apixaban. PMID- 26822675 TI - Weak phonon scattering effect of twin boundaries on thermal transmission. AB - To study the effect of twin boundaries on thermal transmission, thermal conductivities of twinned diamond with different twin thicknesses have been studied by NEMD simulation. Results indicate that twin boundaries show a weak phonon scattering effect on thermal transmission, which is only caused by the additional twin boundaries' thermal resistance. Moreover, according to phonon kinetic theory, this weak phonon scattering effect of twin boundaries is mainly caused by a slightly reduced average group velocity. PMID- 26822676 TI - Impacts of ABCB1 (G1199A) polymorphism on resistance, uptake, and efflux to steroid drugs. AB - 1. P-glycoprotein (P-gp) substrates, including steroid drugs, involve in the inter-individual differences in resistant phenotype. This study was performed to evaluate whether G1199A polymorphism in ABCB1 gene can alter the sensitivity, accumulation, and transepithelial efflux to steroids in LLC-PK1 cells. 2. The stable recombinant LLC-PK1 cell lines transfected with ABCB1 1199G and ABCB1 1199A were used to assess the sensitivity, accumulation, and transepithelial permeability to steroids. 3. The cells transfected with 1199A allele displayed stronger resistance to aldosterone, dexamethasone, and cortisol (2.5-, 2.0-, and 1.6-fold, respectively) than cells overexpressing 1199G allele, while the two types of recombinant cells showed a similar resistance to corticosterone. The accumulation of aldosterone, dexamethasone, and cortisol in recombinant 1199A cells were significantly decreased when compared to 1199G cells (2.9-, 4.4-, and 3.9-fold, respectively). The net efflux ratios of P-gp-mediated aldosterone, dexamethasone, and cortisol in cells expressing 1199A allele were apparently greater than cells transfected with 1199G allele (3.3-, 3.5-, and 4.0-fold, respectively). 4. The impacts of ABCB1 (G1199A) single nucleotide polymorphism on the efflux of P-gp substrates presented as drug-specific. Overall, the transport ability of P-gp-dependent steroid drugs in recombinant model overexpressing variant 1199A allele is stronger in comparison to cells overexpressing wild-type 1199G allele. Therefore, the ABCB1 (G1199A) polymorphism may affect effective steroids concentration in target cells by regulating the drug transport and distribution. PMID- 26822677 TI - Characterisation of P-glycoprotein-9.1 in Haemonchus contortus. AB - BACKGROUND: The existence nematodes of veterinary importance such as Haemonchus contortus resistant to anthelmintic drugs, including the macrocyclic lactones, has become a major concern in animal health. Macrocyclic lactone resistance in H. contortus seems to be multigenic including the active efflux of these drugs by P glycoproteins, members of the ABC transporter family, present in this parasite. The goals of the present work were to determine the activity of H. contortus P glycoprotein 9.1 (Hco-PGP-9.1) and its interaction with the avermectins, ivermectin, abamectin, and also the milbemycin, moxidectin. Additionally, the localisation of Hco-PGP-9.1 was sought in adult worms. METHODS: Hco-Pgp-9.1 was cloned and expressed in mammalian cells and its expression profile was determined at the transcriptional and protein level by qRT-PCR and Western-blot, respectively. The nematode transport activity was assessed using the tracer dye Rhodamine 123. A ligand competition assay between different macrocyclic lactones and Rhodamine 123 was used to establish whether or not there was interaction between Hco-PGP-9.1 and the avermectins (abamectin and ivermectin) or moxidectin. In addition, immunostaining was carried out to localise Hco-PGP-9.1 expression in the transgenic cells and in adult female parasites. RESULTS: Hco-PGP-9.1 was expressed in the cell membrane of the transfected host cells and was able to extrude Rhodamine 123. Ivermectin and abamectin, but not moxidectin, had a pronounced inhibitory effect on the ability of Hco-PGP-9.1 to transport Rhodamine 123. Antibodies raised against Hco-PGP-9.1 epitopes localised to the uterus of adult female H. contortus. CONCLUSIONS: These results suggest a strong interaction of the avermectins with Hco-PGP-9.1. However, possibly due to its physico-chemical properties, moxidectin had markedly less effect on Hco-PGP-9.1. Because of the greater interaction of the avermectins than moxidectin with this transporter, it is more likely to contribute to avermectin resistance than to moxidectin resistance in H. contortus. Possible over expression of Hco-PGP-9.1 in the female reproductive system in resistant worms could reduce paralysis of the uterus by macrocyclic lactones, allowing continued egg release in drug challenged resistant worms. PMID- 26822678 TI - Rate of progression of total, upper, and lower visual field defects in patients with open-angle glaucoma and high myopia. AB - PURPOSE: We evaluated the rate of progression of total, upper, and lower visual field defects in patients with treated primary open-angle glaucoma (POAG) with high myopia (HM). SUBJECTS AND METHODS: Seventy eyes of 70 POAG patients with HM [<=-8 diopters (D)] were examined. The mean deviation (MD) slope and the upper and lower total deviation (upper TD, lower TD) slopes of the Humphrey Field Analyzer were calculated in patients with high-tension glaucoma (HTG) (>21 mmHg) versus normal-tension glaucoma (NTG) (<=21 mmHg). The mean age of all the patients (29 eyes with HTG and 41 eyes with NTG) was 48.5 +/- 9.6 years. The MD slope, and upper and lower TD slopes of the HM group were compared to those of the non-HM group (NHM) (>-8 D) selected from 544 eyes in 325 age-matched POAG patients. In all, 70 eyes with HM and NHM were examined. RESULTS: The mean MD slope was -0.33 +/- 0.33 dB/year in the HM, and -0.38 +/- 0.49 dB/year in the NHM. There were no statistical differences between the HM and NHM (p = 0.9565). In the comparison of HTG versus NTG patients in both groups, the MD slope, and upper and lower TD slopes were similar. CONCLUSIONS: The rate of progression of total, upper, and lower visual field defects was similar among patients with HM and NHM. Although HM is a risk factor for the onset of glaucoma, HM may not be a risk factor for progression of visual field defects as assessed by the progression rate under treatment. PMID- 26822679 TI - Au/TiO2 nanobelt heterostructures for the detection of cancer cells and anticancer drug activity by potential sensing. AB - Cancer is a cell dysfunction disease. The detection of cancer cells is extremely important for early diagnosis and clinical treatments. At present, the pretreatment for the detection of cancer cells is costly, complicated and time consuming. As different species of the analytes may give rise to specific voltammetric signals at distinctly different potentials, simple potential sensing has the specificity to detect different cellular species. By taking advantage of the different electrochemical characteristics of normal cells, cancer cells and biointeractions between anticancer drugs and cancer cells, we develop a specific, sensitive, direct, cost-effective and rapid method for the detection of cancer cells by electrochemical potential sensing based on Au/TiO2 nanobelt heterostructure electrodes that will be of significance in early cancer diagnosis, in vitro screening of anticancer drugs and molecular biology research. PMID- 26822680 TI - Authors' reply to Brusasco and colleagues and Quanjer and colleagues. PMID- 26822681 TI - Simultaneous Determination of Piperine, Capsaicin, and Dihydrocapsaicin in Korean Instant-Noodle (Ramyun) Soup Base Using High-Performance Liquid Chromatography with Ultraviolet Detection. AB - A simultaneous analytical method for piperine, capsaicin, and dihydrocapsaicin in Korean instant-noodle soup base using HPLC was validated in terms of precision, accuracy, sensitivity, and linearity. The HPLC separation was performed on a reversed-phase C18 column (5 MUm particle size, 4.6 mm id, 250 mm length) using a UV detector fixed at 280 nm. The LOD and LOQ of the HPLC analyses ranged from 0.25 to 1.03 mg/kg. The intraday and interday precisions of the individual piperine, capsaicin, and dihydrocapsaicin were <10.55%, and the recovery values ranged from 85.43 to 94.68%. The calibration curves exhibited good linearity (r(2) = 0.999) within the tested ranges. These results suggest that the analytical method in this study can be used to classify Korean instant noodles based on their levels of spiciness. PMID- 26822682 TI - Three new cases of terminal deletion of the long arm of chromosome 7 and literature review to correlate genotype and phenotype manifestations. AB - Partial monosomy of the long arm of chromosome 7 has been characterized by wide phenotypic manifestations, but holoprosencephaly (HPE) and sacral agenesis have frequently been associated with this chromosomal deletion. A clear relationship between genotype and phenotype remains to be defined in the 7q deletion syndrome. Three patients (1, 2, and 3) were investigated with 7q terminal deletion and compared with similar deletion cases in the literature in order to stratify the phenotypes associated with 7q35 and 7q36 terminal deletion patients. Patients 1, 2, and 3 were carrying a de novo terminal deletion at bands 7q36.2, 7q35, and 7q36.1, respectively. In patient 3, a small Xq28 duplication was also identified by array-CGH. Our patients presented with heterogeneous phenotypic manifestations, which could imply the possible role of environmental factors (multifactorial inheritance), structural variations in the non-coding regions, penetrance, and/or polymorphism. The varying length of deletion was also taken into account. Growth retardation was the most frequent symptom found in both 7q35 and 7q36 patients we reviewed. The occurrence of HPE and sacral malformation together was seen in less than 10% of the reviewed cases in both kinds of deletion. HPE was associated mainly in cases with an unbalanced translocation. PMID- 26822683 TI - Discrepancies between one stage assay and chromogenic substrate assay in patients treated with recombinant or plasma-derived FVIII and usefulness of a specific standard in ReFacto AF(r) -treated patients. PMID- 26822684 TI - Perceptual commensuration in decision tables. AB - This paper calls attention to design features that could enhance the helpfulness of the decision table to decision makers trying to get a better intuitive grasp of the choices facing them. The experiments reported here show that the grey scale is more facilitative than the number scale for problem comprehension as measured by the identification of dominance and the identification of non additivity, each of which requires a view of the decision problem that is sensitive to patterns across attributes. Additional design features that could enhance the decision makers' grasp of the choices facing them are suggested for further research. PMID- 26822685 TI - Most children with eosinophilic esophagitis have a favorable outcome as young adults. AB - The disease progression of eosinophilic esophagitis (EoE) from childhood into adulthood is unclear. To determine the clinical outcome of patients who were diagnosed with EoE as children, and who now are young adults. Children (<18 years old) diagnosed with EoE were enrolled in a prospective registry on demographics, presenting symptoms, and endoscopic/histologic findings. Subjects who now are adults (>=18 years old) were identified, and a structured telephone interview was conducted to obtain follow-up data on symptom prevalence (dysphagia to solids and liquids, nausea/vomiting, abdominal pain, and heartburn/regurgitation), food impaction, medication usage, health-care utilization, and resolution of atopy/food allergies. A favorable outcome was defined if EoE symptoms were resolved or improved by subjects' assessment. Unfavorable outcomes was defined as symptoms same or worse. Clinical variables that predicted a favorable outcome as an adult were examined. Mayo Dysphagia Scale (MDQ-30: scored 0-100) was administered to validate the outcome assessment. Mantel-Haenszel odds ratio and unpaired t-test were used. Fifty-eight subjects (64% male) who met study criteria were enrolled. Mean age at diagnosis was 12 years (range 4-17) and mean duration of follow-up was 8.3 years (2-16). As children, the most common presenting symptoms were abdominal pain (54%), dysphagia (33%), and vomiting (24%). As young adults, 47 subjects (81%) had a favorable outcome. Total MDQ-30 scores were 4.6 (0-30) and 14.1 (0-50) in subjects with favorable outcome and unfavorable outcome, respectively (P = 0.015). Two-thirds of subjects did not use steroids or proton pump inhibitors in the preceeding 12 months. Male children with EoE were four times more likely to have a favorable outcome as young adults compared with female children. Females were more likely to report nausea/vomiting as young adults (odds ratio 3.23, CI 0.97-10.60). Of all presenting symptoms in EoE children, dysphagia was the most likely to persist into adulthood (odds ratio 6.29, CI 1.85-21.38). Eighty one percent of EoE children had a favorable outcome as young adults. Most patients with symptom resolution did not require any form of steroid therapy or seek healthcare. PMID- 26822687 TI - Long-term outcomes of health-related quality of life following diverse thrombotic microangiopathy syndromes. PMID- 26822688 TI - Current trends in outwitting resistance development in Candida infections through photodynamic and short peptide therapies: a strategic-shift from conventional antifungal agents. AB - Disequilibrium in the human debilitated immune system favors proliferation of invasive Candida species, a major therapeutic challenge due to development of resistance to several conventional antifungal agents (CAA) worldwide. Multiple mutations observed at specific loci that are targets for CAA are recognized as sources of drug resistance. This has prompted a shift from CAA, to diverse combination therapies, photodynamic and short peptide therapies capable of triggering specific apoptotic reactions within candidal cells. In this review, new designs and combination of short peptide (SP) with CAA as well as current application of photodynamic inactivation (PDI) against Candida species geared at generating reactive species of oxygen (ROS) and nitrogen (RNS) are discussed. It is observed that oxidative and nitrosative stresses provides a superior broad candidacidal effects for eradication of drug-resistant Candida species. The mechanism and limitations in these strategic approaches over CAA is also discussed. PMID- 26822689 TI - Six3 regulates optic nerve development via multiple mechanisms. AB - Malformations of the optic nerve lead to reduced vision or even blindness. During optic nerve development, retinal ganglion cell (RGC) axons navigate across the retina, exit the eye to the optic stalk (OS), and cross the diencephalon midline at the optic chiasm en route to their brain targets. Many signalling molecules have been implicated in guiding various steps of optic nerve pathfinding, however much less is known about transcription factors regulating this process. Here we show that in zebrafish, reduced function of transcription factor Six3 results in optic nerve hypoplasia and a wide repertoire of RGC axon pathfinding errors. These abnormalities are caused by multiple mechanisms, including abnormal eye and OS patterning and morphogenesis, abnormal expression of signalling molecules both in RGCs and in their environment and anatomical deficiency in the diencephalic preoptic area, where the optic chiasm normally forms. Our findings reveal new roles for Six3 in eye development and are consistent with known phenotypes of reduced SIX3 function in humans. Hence, the new zebrafish model for Six3 loss of function furthers our understanding of the mechanisms governing optic nerve development and Six3-mediated eye and forebrain malformations. PMID- 26822690 TI - Transcriptome and comparative gene expression analysis of Phyllostachys edulis in response to high light. AB - BACKGROUND: Photosynthesis plays a vital role as an energy source for plant metabolism, and its efficiency may be drastically reduced owing to abiotic stresses. Moso bamboo (Phyllostachys edulis), is a renewable and versatile resource with significant ecological and economic value, which encounters high light stress with large amplitude in natural environment. However, the gene expression profiles in response to high light were elusive in bamboo. RESULTS: We firstly performed physiological experiments on moso bamboo leaves treated with high light (1200 MUmol . m(-2) . s(-1)). Based on the physiological results, three samples of leaves treated with high light for 0 h (CK), 0.5 h (0.5H), and 8 h (8H) were selected to perform further high-throughput RNA sequencing (RNA-Seq), respectively. Then, the transcriptomic result demonstrated that the most genes were expressed at a statistically significant value (FPKM >= 1) and the RNA-Seq data were validated via quantitative real time PCR. Moreover, some significant gene expression changes were detected. For instance, 154 differentially expressed genes were detected in 0.5H vs. CK, those in 8H vs. CK were 710, and 429 differentially expressed genes were also identified in 0.5H vs.8 H. Besides, 47 gene annotations closely related to photosynthesis were refined, including 35 genes annotated as light-harvesting chlorophyll a/b-binding (LHC) proteins, 9 LHC like proteins and 3 PsbSs. Furthermore, the pathway of reactive oxygen species (ROS) in photosynthesis was further analyzed. A total of 171 genes associated with ROS-scavenging were identified. Some up-regulated transcript factors, such as NAC, WRKY, AR2/ERF, and bHLH, mainly concentrated in short-term response, while C2H2, HSF, bZIP, and MYB were largely involved in short and middle terms response to high light. CONCLUSION: Based on the gene expression analysis of moso bamboo in response to high light, we thus identified the global gene expression patterns, refined the annotations of LHC protein, LHC-like protein and PsbS, detected the pathway of ROS as well as identified ROS-scavenging genes and transcription factors in the regulation of photosynthetic and related metabolisms. These findings maybe provide a starting point to interpret the molecular mechanism of photosynthesis in moso bamboo under high light stress. PMID- 26822691 TI - Retrospective analysis of the effectiveness and costs of traditional treatments for moderate-to-severe psoriasis: A single-center, Italian study. AB - BACKGROUND: Current guidelines recommend the use of systemic therapy and phototherapy for the treatment of moderate-to-severe plaque psoriasis. OBJECTIVES: To evaluate the effectiveness, impact on health status perception, and costs of traditional systemic therapies and phototherapy in real-life patients with moderate-to-severe psoriasis. METHODS: Retrospective analysis of data from 100 psoriatic patients referring to a dermatology clinic in Italy and treated with traditional therapies. RESULTS: Patients were predominantly treated with cyclosporine (72%). Cyclosporine was associated with fewer treatment discontinuations due to lack of efficacy (37%) compared with methotrexate (65%), acitretin (67%) and phototherapy (50%). Rates of treatment discontinuation due to adverse events were: cyclosporine (24%), methotrexate (9%), acitretin (25%) and phototherapy (0%). Improvements in PASI scores were comparable between treatments. The need for topical therapy was reduced with cyclosporine versus other therapies (35% vs 71%, p = 0.0009); respectively, 33% of patients treated with cyclosporine versus 14% of patients receiving other therapies perceived an improvement in their health status (p = 0.0018). Mean total per-patient direct costs of the first treatment cycle were higher with cyclosporine than with other therapies (?1812.85 vs ?648.90, p < 0.0001). CONCLUSIONS: Cyclosporine was effective even if more expensive than other traditional therapies. Nevertheless patients' perception of improvement was quite low. PMID- 26822692 TI - Increased red blood cell distribution width in patients with polymyositis is correlated with disease activity. PMID- 26822693 TI - Editorial Comment. PMID- 26822695 TI - Use of platelet-rich plasma in deep second- and third-degree burns. AB - Unfortunately burns are a common occurrence, leading to scarring or death. Platelet-rich plasma (PRP) contains many growth factors that can accelerate wound healing. We analyzed the use of PRP in deep second-degree (dSD), deep second degree associated with diabetes mellitus (dSDD), and third-degree (TD) burns in rats. Sixty syngeneic rats divided into three groups (dSD, dSDD, and TD) were burned, half receiving topical PRP and half being used as control; 10 additional rats per group were used for PRP preparation. On day 21, the animals were sacrificed and skin biopsies were collected. dSD and dSDD wounds treated with PRP showed faster wound closure, reduction in CD31-, CD68-, CD163-, MPO-, and in TGF beta-positive cells, and an increase in MMP2-positive cells. The neo-epidermis was thinner in the control of both the dSD and dSDD groups and granulation tissue was less reduced in the control of both the dSDD and TD groups. These results indicate that PRP can accelerate the healing process in dSD and dSDD, but not in TD burns. PMID- 26822696 TI - Bacillus flexus outbreak in a tertiary burn center. PMID- 26822694 TI - PLEKHA7 defines an apical junctional complex with cytoskeletal associations and miRNA-mediated growth implications. AB - E-cadherin-p120 catenin complexes are essential for adherens junction (AJ) formation and for the maintenance of the normal epithelial phenotype. PLEKHA7 was originally identified as a member of this complex that tethers microtubules to the AJs and supports their overall integrity. Recently, we revealed that PLEKHA7 regulates cellular behavior via miRNAs by associating with the microprocessor complex at the apical zonula adherens (ZA). We have also identified a new set of PLEKHA7 interacting partners at the apical ZA, via proteomics. Our analysis shows that the main groups of proteins associating with PLEKHA7 are cytoskeletal related and RNA-binding proteins. Here, we provide extended evidence for association of PLEKHA7 with several of these proteins. We also show that PLEKHA7 loss activates the actin regulator cofilin in a p120-dependent manner, providing an explanation for the effects of PLEKHA7 on the cortical actin ring. Interestingly, PLEKHA7 regulates the levels and associates with PP1alpha, a phosphatase responsible for cofilin activation. Finally, we clarify the mode of regulation of the oncogenic miR-19a by PLEKHA7. Overall, our findings support a multi-layered role of PLEKHA7 in converging cytoskeletal dynamics and miRNA mediated growth regulation at the ZA, with potentially critical implications in cancer that warrant further investigation. PMID- 26822697 TI - The speech-language pathologist's role in multidisciplinary burn care: An international perspective. AB - PURPOSE: To explore international practices of speech-language pathology (SLP) within burn care in order to provide direction for education, training and clinical practice of the burns multidisciplinary team (MDT). METHOD(S): A 17-item online survey was designed by two SLPs experienced in burn care with a range of dichotomous, multiple choice and open-ended response questions investigating the availability and scope of practice for SLPs associated with burn units. The survey was distributed via professional burn association gatekeepers. All quantitative data gathered were analysed using descriptive statistics and qualitative data were analysed using content analysis. RESULT(S): A total of 240 health professionals, from 6 different continents (37 countries) participated within the study. All continents reported access to SLP services. Referral criteria for SLP were largely uniform across continents. The most dominant area of SLP practice was assessment and management of dysphagia, which was conducted in concert with other members of the MDT. CONCLUSION: SLP has an international presence within burn care that is currently still emerging. PMID- 26822698 TI - Left ventricular volumes by echocardiography in chronic aortic and mitral regurgitations. AB - Objectives Cut-off values for left ventricular (LV) dimensions indicating severe valve regurgitation have not been defined. The aim of this study was to establish echocardiographic cut-off values for LV dimensions indicating severe chronic aortic (AR) or mitral (MR) regurgitation. Design The hemodynamic significance was confirmed by documented reduction of end-diastolic volume (EDV) and symptom relief after surgery. Eighty-three patients with moderate or severe regurgitation (AR, n = 41; MR, n = 42) without other cardiac conditions underwent prospectively two-dimensional (2DE), real-time three-dimensional (RT3DE) echocardiography and cardiovascular magnetic resonance (CMR) exams within 4 h. Results The relationship between EDVCMR and EDV2DE and EDVRT3DE were strong (R 0.95 and 0.91). EDV index cut-offs for 2DE/RT3DE >87/104 ml/m(2) identified AR patients with severe regurgitation with a positive likelihood ratio (PLR) of 5.0/5.0. The corresponding in patients with MR EDV index cut-offs were >69/87 ml/m(2) with a PLR of 14.9/5.5. LV linear dimensions could not identify patients with severe regurgitation. Conclusions LV volumes by echocardiography can support the diagnosis of severe chronic regurgitation. Importantly, other causes for LV enlargement have to be considered. PMID- 26822699 TI - The association between tobacco, alcohol, and drug use, stress, and depression among uninsured free clinic patients: U.S.-born English speakers, non-U.S.-born English speakers, and Spanish speakers. AB - The abuse of substances is a significant public health issue. Perceived stress and depression have been found to be related to the abuse of substances. The purpose of this study is to examine the prevalence of substance use (i.e., alcohol problems, smoking, and drug use) and the association between substance use, perceived stress, and depression among free clinic patients. Patients completed a self-administered survey in 2015 (N = 504). The overall prevalence of substance use among free clinic patients was not high compared to the U.S. general population. U.S.-born English speakers reported a higher prevalence rate of tobacco smoking and drug use than did non-U.S.-born English speakers and Spanish speakers. Alcohol problems and smoking were significantly related to higher levels of perceived stress and depression. Substance use prevention and education should be included in general health education programs. U.S.-born English speakers would need additional attention. Mental health intervention would be essential to prevention and intervention. PMID- 26822700 TI - The importance of correcting for signal drift in diffusion MRI. AB - PURPOSE: To investigate previously unreported effects of signal drift as a result of temporal scanner instability on diffusion MRI data analysis and to propose a method to correct this signal drift. METHODS: We investigated the signal magnitude of non-diffusion-weighted EPI volumes in a series of diffusion-weighted imaging experiments to determine whether signal magnitude changes over time. Different scan protocols and scanners from multiple vendors were used to verify this on phantom data, and the effects on diffusion kurtosis tensor estimation in phantom and in vivo data were quantified. Scalar metrics (eigenvalues, fractional anisotropy, mean diffusivity, mean kurtosis) and directional information (first eigenvectors and tractography) were investigated. RESULTS: Signal drift, a global signal decrease with subsequently acquired images in the scan, was observed in phantom data on all three scanners, with varying magnitudes up to 5% in a 15-min scan. The signal drift has a noticeable effect on the estimation of diffusion parameters. All investigated quantitative parameters as well as tractography were affected by this artifactual signal decrease during the scan. CONCLUSION: By interspersing the non-diffusion-weighted images throughout the session, the signal decrease can be estimated and compensated for before data analysis; minimizing the detrimental effects on subsequent MRI analyses. Magn Reson Med 77:285-299, 2017. (c) 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. PMID- 26822701 TI - Conformational Dynamics, Ligand Binding and Effects of Mutations in NirE an S Adenosyl-L-Methionine Dependent Methyltransferase. AB - Heme d1, a vital tetrapyrrol involved in the denitrification processes is synthesized from its precursor molecule precorrin-2 in a chemical reaction catalysed by an S-adenosyl-L-methionine (SAM) dependent Methyltransferase (NirE). The NirE enzyme catalyses the transfer of a methyl group from the SAM to uroporphyrinogen III and serves as a novel potential drug target for the pharmaceutical industry. An important insight into the structure-activity relationships of NirE has been revealed by elucidating its crystal structure, but there is still no understanding about how conformational flexibility influences structure, cofactor and substrate binding by the enzyme as well as the structural effects of mutations of residues involved in binding and catalysis. In order to provide this missing but very important information we performed a comprehensive atomistic molecular dynamics study which revealed that i) the binding of the substrate contributes to the stabilization of the structure of the full complex; ii) conformational changes influence the orientation of the pyrrole rings in the substrate, iii) more open conformation of enzyme active site to accommodate the substrate as an outcome of conformational motions; and iv) the mutations of binding and active site residues lead to sensitive structural changes which influence binding and catalysis. PMID- 26822702 TI - (19)F NMR and DFT Analysis Reveal Structural and Electronic Transition State Features for RhoA-Catalyzed GTP Hydrolysis. AB - Molecular details for RhoA/GAP catalysis of the hydrolysis of GTP to GDP are poorly understood. We use (19)F NMR chemical shifts in the MgF3(-) transition state analogue (TSA) complex as a spectroscopic reporter to indicate electron distribution for the gamma-PO3(-) oxygens in the corresponding TS, implying that oxygen coordinated to Mg has the greatest electron density. This was validated by QM calculations giving a picture of the electronic properties of the transition state (TS) for nucleophilic attack of water on the gamma-PO3(-) group based on the structure of a RhoA/GAP-GDP-MgF3(-) TSA complex. The TS model displays a network of 20 hydrogen bonds, including the GAP Arg85' side chain, but neither phosphate torsional strain nor general base catalysis is evident. The nucleophilic water occupies a reactive location different from that in multiple ground state complexes, arising from reorientation of the Gln-63 carboxamide by Arg85' to preclude direct hydrogen bonding from water to the target gamma-PO3(-) group. PMID- 26822703 TI - DNA methylation in the pathophysiology of hyperphenylalaninemia in the PAH(enu2) mouse model of phenylketonuria. AB - Phenylalanine hydroxylase deficient phenylketonuria (PKU) is the paradigm for a treatable inborn error of metabolism where maintaining plasma phenylalanine (Phe) in the therapeutic range relates to improved clinical outcomes. While Phe is the presumed intoxicating analyte causal in neurologic damage, the mechanism(s) of Phe toxicity has remained elusive. Altered DNA methylation is a recognized response associated with exposure to numerous small molecule toxic agents. Paralleling this effect, we hypothesized that chronic Phe over-exposure in the brain would lead to aberrant DNA methylation with secondary influence upon gene regulation that would ultimately contribute to PKU neuropathology. The PAH(enu2) mouse models human PKU with intrinsic hyperphenylalaninemia, abnormal response to Phe challenge, and neurologic deficit. To examine this hypothesis, we assessed DNA methylation patterns in brain tissues using methylated DNA immunoprecipitation and paired end sequencing in adult PAH(enu2) animals maintained under either continuous dietary Phe restriction or chronic hyperphenylalaninemia. Heterozygous PAH(enu2/WT) litter mates served as controls for normal Phe exposure. Extensive repatterning of DNA methylation was observed in brain tissue of hyperphenylalaninemic animals while Phe restricted animals displayed an attenuated pattern of aberrant DNA methylation. Affected gene coding regions displayed aberrant hypermethylation and hypomethylation. Gene body methylation of noncoding RNA genes was observed and among these microRNA genes were prominent. Of particular note, observed only in hyperphenylalaninemic animals, was hypomethylation of miRNA genes within the imprinted Dlk1-Dio3 locus on chromosome 12. Aberrant methylation of microRNA genes influenced their expression which has secondary effects upon the expression of targeted protein coding genes. Differential hypermethylation of gene promoters was exclusive to hyperphenylalaninemic PAH(enu2) animals. Genes with synaptic involvement were targets of promoter hypermethylation that resulted in down-regulation of their expression. Gene dysregulation secondary to abnormal DNA methylation may be contributing to PKU neuropathology. These results suggest drugs that prevent or correct aberrant DNA methylation may offer a novel therapeutic option to management of neurological symptoms in PKU patients. PMID- 26822705 TI - Real-time sonoelastography findings in a patient with tennis leg: a promising technique in the assessment of muscle rupture. PMID- 26822706 TI - Point-of-care ultrasonography in a physiatric foot clinic. AB - BACKGROUND: Few reports are available for the utility of diagnostic point-of-care (POC) ultrasonography for foot and ankle pain and diagnostic POC ultrasonography in physiatric practice has not yet been demonstrated. AIM: To describe POC musculoskeletal ultrasonographic (US) findings by location of pain among patients presenting to a foot pain clinic and to evaluate the concordance rate between clinical diagnoses and US findings by region of the foot. DESIGN: Retrospective chart review. SETTING: Outpatient clinic. POPULATION: A total of 111 patients with foot and ankle pain. METHODS: Retrospective chart review of clinical notes and data from POC US evaluation of patients who presented to the foot pain clinic between November 2013 and January 2015. US evaluations were performed by two physiatric ultrasonographers. MAIN OUTCOME MEASURES: The concordance rate of clinical diagnosis and findings from US imaging based on the location of foot pain. RESULTS: One hundred eleven patients out of 205 patients who presented to the foot clinic (54.1%) had POC US evaluation during the initial visit. The data was analyzed for patients with a single location of pain excluding 21 patients with pain more than one location. The mean age was 55.1+/-14.3 years with 86.5% being female. The most common location of pain was the hindfoot/ankle (N.=71), followed by forefoot (N.=13) and midfoot (N.=6). The overall concordance rate between clinical and ultrasonographic diagnoses was 62.2% (56/90) with a higher concordance rate in the hindfoot (67.6%) compared to the rest of the foot (50% in midfoot, 38.5% in the forefoot, P=0.042). The most common reasons for discordance (N.=34) were failure to reveal abnormality on US (N.=20, 58%) followed by unexpected US findings (N.=7, 20.6%). CONCLUSIONS: Concordance between clinical evaluation and POC US findings varies depending on the location of foot pain and often no US abnormalities were found in spite of clinical symptoms particularly in forefoot region. CLINICAL REHABILITATION IMPACT: These new findings will enhance the selective application of POC US and improve its clinical utility in physiatric practice. PMID- 26822707 TI - Erythropoietin in bone - Controversies and consensus. AB - Erythropoietin (Epo) is the main hormone that regulates the production of red blood cells (hematopoiesis), by stimulating their progenitors. Beyond this vital function, several emerging roles have been noted for Epo in other tissues, including neurons, heart and retina. The skeletal system is also affected by Epo, however, its actions on bone are, as yet, controversial. Here, we review the seemingly contradicting evidence regarding Epo effects on bone remodeling. We also discuss the evidence pointing to a direct versus indirect effect of Epo on the osteoblastic and osteoclastic cell lineages. The current controversy may derive from a context-dependent mode of action of Epo, namely opposite skeletal actions during bone regeneration and steady-state bone remodeling. Differences in conclusions from the published in-vitro studies may thus relate to the different experimental conditions. Taken together, these studies indicate a complexity of Epo functions in bone cells. PMID- 26822708 TI - The hepatocyte growth factor (HGF)-MET receptor tyrosine kinase signaling pathway: Diverse roles in modulating immune cell functions. AB - Hepatocyte growth factor (HGF) signaling via the MET receptor is essential for embryonic development and tissue repair. On the other hand, deregulated MET signaling promotes tumor progression in diverse types of cancers. Even though oncogenic MET signaling remains the major research focus, the HGF-MET axis has also been implicated in diverse aspects of immune cell development and functions. In the presence of other hematopoietic growth factors, HGF promotes the development of erythroid, myeloid and lymphoid lineage cells and thrombocytes. In monocytes and macrophages responding to inflammatory stimuli, induction of autocrine HGF-MET signaling can contribute to tissue repair via stimulating anti inflammatory cytokine production. HGF-MET signaling can also modulate adaptive immune response by facilitating the migration of Langerhans cells and dendritic cells to draining lymph nodes. However, MET signaling has also been shown to induce tolerogenic dendritic cells in mouse models of graft-versus-host disease and experimental autoimmune encephalomyelitis. HGF-MET axis is also implicated in promoting thymopoiesis and the survival and migration of B lymphocytes. Recent studies have shown that MET signaling induces cardiotropism in activated T lymphocytes. Further understanding of the HGF-MET axis in the immune system would allow its therapeutic manipulation to improve immune cell reconstitution, restore immune homeostasis and to treat immuno-inflammatory diseases. PMID- 26822710 TI - Electrochemical impedance investigation of Ni-free Co-Cr-Mo and Co-Cr-Mo-Ni dental casting alloy for partial removable dental prosthesis frameworks. AB - STATEMENT OF PROBLEM: The pH level of the oral environment influences corrosion in dental materials. Corrosion behaviors of Co-Cr-Mo and Co-Cr-Mo-Ni alloys in different pH environments remain undetermined. PURPOSE: The purpose of this in vitro study was to evaluate the surface properties and corrosion behaviors of Co Cr-Mo and Co-Cr-Mo-Ni dental casting alloys in artificial saliva at pH values of 5.0 and 2.5. MATERIAL AND METHODS: Fifty specimens were divided into 2 groups according to the alloy composition. The surface compositions, hardness values, and microstructures of the alloys were measured before immersion in artificial saliva. The corrosion behaviors of the specimens in artificial saliva at pH values of 5.0 and 2.5 were studied using electrochemical impedance spectroscopy (EIS). The microstructures were examined again after a 7-day immersion test. Data were analyzed by a 1-way analysis of variance (ANOVA) test (alpha=.05). RESULTS: As expected, the relative levels of Co and Cr of the surface composition were higher in the Co-Cr-Mo alloy. The Co-Cr-Mo alloy had statistically higher surface hardness than the Co-Cr-Mo-Ni alloy (P<.05). In the pH 2.5 environment, both of the alloys showed decreased corrosion resistance (P<.05). The microstructure of the Co-Cr-Mo-Ni alloy corroded more than that of the Co-Cr-Mo alloy in the pH 2.5 environment. The oxide-layer corrosion resistance of the Co-Cr-Mo alloy was better than that of the Co-Cr-Mo-Ni alloy in Fusayama artificial saliva solutions at pH values of both 5.0 and 2.5 (P<.05). CONCLUSIONS: The corrosion resistance of the Co-Cr-Mo alloy was better in the oral environment, especially at a low pH value. PMID- 26822709 TI - Anti-metastatic functions of type 1 interferons: Foundation for the adjuvant therapy of cancer. AB - The anti-tumorigenic effects that type 1 interferons (IFN1) elicited in the in vitro studies prompted consideration of IFN1 as a potent candidate for clinical treatment. Though not all patients responded to IFN1, clinical trials have shown that patients with high risk melanoma, a highly refractory solid malignancy, benefit greatly from intermediate IFN1 treatment in regards to relapse-free and distant-metastasis-free survival. The mechanisms by which IFN1 treatment at early stages of disease suppress tumor recurrence or metastatic incidence are not fully understood. Intracellular IFN1 signaling is known to affect cell differentiation, proliferation, and apoptosis. Moreover, recent studies have revealed specific IFN1-regulated genes that may contribute to IFN1-mediated suppression of cancer progression and metastasis. In concert, expression of these different IFN1 stimulated genes may impede numerous mechanisms that mediate metastatic process. Though, IFN1 treatment is still utilized as part of standard care for metastatic melanoma (alone or in combination with other therapies), cancers find the ways to develop insensitivity to IFN1 treatment allowing for unconstrained disease progression. To determine how and when IFN1 treatment would be most efficacious during disease progression, we must understand how IFN1 signaling affects different metastasis steps. Here, we specifically focus on the anti-metastatic role of endogenous IFN1 and parameters that may help to use pharmaceutical IFN1 in the adjuvant treatment to prevent cancer recurrence and metastatic disease. PMID- 26822711 TI - Otolaryngologic Manifestations of Levamisole-Induced Vasculitis. PMID- 26822712 TI - Why Is It So Difficult to Influence the Clinical Management of Hypertension? PMID- 26822713 TI - Effects of Trace Amine-associated Receptor 1 Agonists on the Expression, Reconsolidation, and Extinction of Cocaine Reward Memory. AB - BACKGROUND: As a modulator of dopaminergic system, trace amine-associated receptor 1 has been shown to play a critical role in regulating the rewarding properties of additive drugs. It has been demonstrated that activation of trace amine-associated receptor 1 decreased the abuse-related behaviors of cocaine in rats. However, the role of trace amine-associated receptor 1 in specific stages of cocaine reward memory is still unclear. METHODS: Here, using a cocaine-induced conditioned place preference model, we tested the effects of a selective trace amine-associated receptor 1 agonist RO5166017 on the expression, reconsolidation, and extinction of cocaine reward memory. RESULTS: We found that RO5166017 inhibited the expression but not retention of cocaine-induced conditioned place preference. RO5166017 had no effect on the reconsolidation of cocaine reward memory. Pretreatment with RO5166017 before extinction hindered the formation of extinction long-term memory. RO5166017 did not affect the movement during the conditioned place preference test, indicating the inhibitory effect of RO5166017 on the expression of cocaine-induced conditioned place preference was not caused by locomotion inhibition. Using a cocaine i.v. self-administration model, we found that the combined trace amine-associated receptor 1 partial agonist RO5263397 with extinction had no effect on the following cue- and drug-induced reinstatement of cocaine-seeking behavior. Repeated administration of the trace amine-associated receptor 1 agonist during extinction showed a continually inhibitory effect on the expression of cocaine reward memory both in cocaine induced conditioned place preference and cocaine self-administration models. CONCLUSIONS: Taken together, these results indicate that activation of trace amine-associated receptor 1 specifically inhibited the expression of cocaine reward memory. The inhibitory effect of trace amine-associated receptor 1 agonists on cocaine reward memory suggests that trace amine-associated receptor 1 agonists could be a promising agent to prevent cocaine relapse. PMID- 26822714 TI - Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study. AB - BACKGROUND: Undenatured type II collagen (UC-II) is a nutritional supplement derived from chicken sternum cartilage. The purpose of this study was to evaluate the efficacy and tolerability of UC-II for knee osteoarthritis (OA) pain and associated symptoms compared to placebo and to glucosamine hydrochloride plus chondroitin sulfate (GC). METHODS: One hundred ninety one volunteers were randomized into three groups receiving a daily dose of UC-II (40 mg), GC (1500 mg G & 1200 mg C), or placebo for a 180-day period. The primary endpoint was the change in total Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) from baseline through day 180 for the UC-II group versus placebo and GC. Secondary endpoints included the Lequesne Functional Index (LFI), the Visual Analog Scale (VAS) for pain and the WOMAC subscales. Modified intent-to-treat analysis were performed for all endpoints using analysis of covariance and mixed model repeated measures, while incremental area under the curve was calculated by the intent-to-treat method. RESULTS: At day 180, the UC-II group demonstrated a significant reduction in overall WOMAC score compared to placebo (p = 0.002) and GC (p = 0.04). Supplementation with UC-II also resulted in significant changes for all three WOMAC subscales: pain (p = 0.0003 vs. placebo; p = 0.016 vs. GC); stiffness (p = 0.004 vs. placebo; p = 0.044 vs. GC); physical function (p = 0.007 vs. placebo). Safety outcomes did not differ among the groups. CONCLUSION: UC-II improved knee joint symptoms in knee OA subjects and was well-tolerated. Additional studies that elucidate the mechanism for this supplement's actions are warranted. TRIAL REGISTRATION: CTRI/2013/05/003663 ; CTRI/2013/02/003348 . PMID- 26822716 TI - A survey of blood pressure parameters after aneurysmal subarachnoid hemorrhage. AB - : Purpose/aim: Blood pressure (BP) regulation is recommended following aneurysmal subarachnoid hemorrhage (aSAH) to prevent re-bleeding and to treat delayed cerebral ischemia. However, optimal BP thresholds are not well established. There is also variation with regard to the BP component (e.g. systolic vs. mean) that is targeted or manipulated. MATERIALS AND METHODS: An 18-question survey was distributed to physicians and advanced practitioner members of the Neurocritical Care Society. Respondents were asked which BP parameter they manipulated and what their thresholds were in different clinical scenarios. They were also asked whether they were influenced by the presence of incidental aneurysms. Answers were analyzed for differences in training background and treatment setting. RESULTS: There were 128 responses. The majority were neurointensivists (47 neurology and 37 non-neurology) and treated patients in dedicated neurointensive care units (n = 98). Systolic BP (SBP) was preferred over mean arterial pressure (MAP). Prior to aneurysm treatment, SBP limits ranged from 140 to 180 mm Hg. After aneurysm treatment, SBP limits ranged from 160 to 240 mm Hg. The maximum and minimum MAPs varied by as much as 50%. Nearly two-thirds of the respondents were influenced by the presence of incidental aneurysms. Training background influenced tolerance to BP limits with neurology-trained neurointensivists accepting higher BP limits when treating delayed ischemia ( p = .018). They were also more likely to follow SBP ( p = .018) and have a limit of 140 mm Hg prior to aneurysm treatment ( p = .001). CONCLUSIONS: There is large practice variability in BP management following aSAH. There is also uncertainty over the importance of incidental aneurysms. Further research could evaluate whether this variability has clinical significance. PMID- 26822715 TI - The acceptability and cost of a home-based chlamydia retesting strategy: findings from the REACT randomised controlled trial. AB - BACKGROUND: Chlamydia retesting three months after treatment is recommended to detect reinfections, but retesting rates are typically low. The REACT (retest after Chlamydia trachomatis) randomised trial demonstrated that home-based retesting using postal home-collection kits and SMS reminders, resulted in substantial improvements in retesting rates in women, heterosexual men and men who have sex with men (MSM), with detection of more repeat positive tests compared with SMS reminder alone. In the context of this trial, the acceptability of the home-based strategy was evaluated and the costs of the two strategies were compared. METHODS: REACT participants (200 women, 200 heterosexual men, 200 MSM) were asked to complete an online survey that included home-testing acceptability and preferred methods of retesting. The demographics, sexual behaviour and acceptability of home collection were compared between those preferring home testing versus clinic-based retesting or no preference, using a chi-square test. The costs to the health system of the clinic-based and home retesting strategies and the cost per infection for each were also compared. RESULTS: Overall 445/600 (74 %) participants completed the survey; 236/445 from the home-testing arm, and 141 of these (60 %) retested at home. The majority of home arm retesters were comfortable having the kit posted to their home (86 %); found it easy to follow the instructions and collect the specimens (96 %); were confident they had collected the specimens correctly (90 %); and reported no problems (70 %). Most (65 %) preferred home retesting, 21 % had no preference and 14 % preferred clinic retesting. Comparing those with a preference for home testing to those who didn't, there were significant differences in being comfortable having a kit sent to their home (p = 0.045); not having been diagnosed with chlamydia previously (p = 0.030); and living with friends (p = 0.034). The overall cost for the home retest pathway was $154 (AUD), compared to $169 for the clinic-based retesting pathway and the cost per repeat infection detected was $1409 vs $3133. CONCLUSIONS: Among individuals initially diagnosed with chlamydia in a sexual health clinic setting, home-based retesting was shown to be highly acceptable, preferred by most participants, and cost-efficient. However some clients preferred clinic-based testing, often due to confidentiality concerns in their home environment. Both options should be provided to maximise retesting rates. TRIAL REGISTRATION: The trial was registered with the Australia New Zealand Clinical Trials Registry on September 9, 2011: ACTRN12611000968976. PMID- 26822717 TI - Synthesis and Potent Anti-HCMV Activity of 2',5',5'-trifluoro-3'-hydroxy-apiosyl Nucleoside Phosphonic Acid Analogues. AB - As antiviral nucleosides containing a fluorine atom at 2'-position are endowed with increased stabilization of glycosyl bond, it was of interest to investigate the influence of three fluorine atoms at 2'- and 5'-positions of apiosyl nucleoside phosphonate analogues. Various pyrimidine and purine 2',5',5' trifluoro-3'-hydroxy-apiose nucleoside phosphonic acid analogues were synthesized from 1,3-dihydroxyacetone. Electrophilic fluorination of lactone was performed using N-fluorodibenzenesulfonimide. Difluorophosphonation was performed by direct displacement of triflate intermediate with diethyl(lithiodifluoromethyl) phosphonate to give the corresponding (alpha,alpha-difluoroalkyl) phosphonate. Condensation successfully proceeded from a glycosyl donor with persilylated bases to yield nucleoside phosphonate analogues. Deprotection of diethyl phosphonates provided the final phosphonic acid sodium salts. The synthesized nucleoside analogues were subjected to antiviral screening against various viruses. PMID- 26822718 TI - Lactobacillus plantarum NCU116 Attenuates Cyclophosphamide-Induced Immunosuppression and Regulates Th17/Treg Cell Immune Responses in Mice. AB - The balance of T helper cells 17 (Th17)/regulatory T cells (Treg) plays a key role in maintaining a normal immune response. It is well-known that cyclophosphamide (CTX) applied at high dose often damages the immune system by inhibiting immune cell proliferation. In this study, the immunomodulating effects of Lactobacillus plantarum NCU116 in CTX-induced immunosuppression mice were investigated. Results showed that the levels of cytokines interleukin (IL)-17 and IL-21 were significantly increased after 10 days of treatment with a high dose of NCU116 (46.92 +/- 4.28 and 119.92 +/- 10.89, respectively) compared with the model group (36.20 +/- 2.63, 61.00 +/- 6.92, respectively), and the levels of cytokines IL-23 and TGF-beta3 of the three NCU116 treatment groups were significantly higher than that of the model group (90.48 +/- 6.33 and 140.45 +/- 14.30, respectively) (p < 0.05) and close to 62 and 69% of the normal group's level (140.98 +/- 14.74 and 266.95 +/- 23.11, respectively) at 10 days. The bacterium was also found to increase the expression levels of Th17 immune response and Treg immune response specific transcription factors RORgammat and Foxp3. In addition, the bacterium significantly increased the number of CD4(+)T cells and dendrtic cells (DCs) and up-regulated mRNA expression of Toll-like receptors (TLRs). These findings demonstrated that NCU116 has the potential ability to enhance intestinal mucosa immunity and regulate the Th17/Treg balance, which may be attributed to the TLR pathway in DCs. PMID- 26822719 TI - Arrhythmias in 2015: Advances in drug, ablation, and device therapy for cardiac arrhythmias. PMID- 26822722 TI - Risk factors: Periodontitis increases risk of a first MI. PMID- 26822720 TI - Role of biomechanical forces in the natural history of coronary atherosclerosis. AB - Atherosclerosis remains a major cause of morbidity and mortality worldwide, and a thorough understanding of the underlying pathophysiological mechanisms is crucial for the development of new therapeutic strategies. Although atherosclerosis is a systemic inflammatory disease, coronary atherosclerotic plaques are not uniformly distributed in the vascular tree. Experimental and clinical data highlight that biomechanical forces, including wall shear stress (WSS) and plaque structural stress (PSS), have an important role in the natural history of coronary atherosclerosis. Endothelial cell function is heavily influenced by changes in WSS, and longitudinal animal and human studies have shown that coronary regions with low WSS undergo increased plaque growth compared with high WSS regions. Local alterations in WSS might also promote transformation of stable to unstable plaque subtypes. Plaque rupture is determined by the balance between PSS and material strength, with plaque composition having a profound effect on PSS. Prospective clinical studies are required to ascertain whether integrating mechanical parameters with medical imaging can improve our ability to identify patients at highest risk of rapid disease progression or sudden cardiac events. PMID- 26822724 TI - Evidence of viscoplastic behavior of exfoliated graphite nanofluids. AB - The rheological behavior of ethylene glycol-based nanofluids containing exfoliated graphite nanoplatelets has been carried out using a cone-plate Physica MCR rheometer. Initial experiments based on flow curves were carried out, the flow curves were based on the controlled shear stress model, these tests show that the studied nanofluids present non-Newtonian shear thinning behavior with yield stress. Furthermore, linear viscoelastic experiments were conducted in order to determine the viscoelastic behavior: using strain sweep and frequency sweep tests the storage and loss modulus were determined. The fractal dimension (Df) was estimated from the suspension static yield-stress and volume fraction (phi) dependence, and was determined to be Df = 2.36, a value consistent with a process of aggregation of RLCA type (reaction limited cluster aggregation). This value is unusual if compared with other nanofluids, and can be regarded as a result of the bidimensionality of the suspended nanoplatelets. Finally, creep recovery tests and mechanical models confirm the viscoplastic nature of our nanofluids, a feature never shown so far for this type of systems, increasing the solid-like character in the range of concentrations studied if compared with other nanofluids reported in the literature. This is a result of the combination of a remarkable internal structure and strong interactions, which evidence an unexpected behaviour sharing many solid-like features. PMID- 26822723 TI - Considerations for cardiac device lead extraction. AB - Extraction of cardiovascular implantable electronic device leads is the removal of a lead that has been implanted for >1 year or that requires more than a standard stylet. The number of these procedures has greatly increased over the past few decades owing to the growing demand for primary and secondary implantations in ageing populations, and an accompanying rise in revisions for complications, infections, and lead advisory safety alerts. In this Review, we present the most common indications and techniques used for extraction. Particular consideration is given to the extraction of leads with large vegetations, recalled leads, stented leads, and those placed in the coronary sinus. We also summarize the most relevant and contemporary data on safety, efficacy, and outcomes of lead extraction. PMID- 26822726 TI - Regarding "Clinical and Imaging Follow-Up of Patients with Coiled Basilar Tip Aneurysms Up to 20 Years". PMID- 26822725 TI - Quantitative Analysis of Global Proteome and Lysine Acetylome Reveal the Differential Impacts of VPA and SAHA on HL60 Cells. AB - Valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) are both HDAC inhibitors (HDACi). Previous studies indicated that both inhibitors show therapeutic effects on acute myeloid leukaemia (AML), while the differential impacts of the two different HDACi on AML treatment still remains elusive. In this study, using 3-plex SILAC based quantitative proteomics technique, anti acetyllysine antibody based affinity enrichment, high resolution LC-MS/MS and intensive bioinformatic analysis, the quantitative proteome and acetylome in SAHA and VPA treated AML HL60 cells were extensively studied. In total, 5,775 proteins and 1,124 lysine acetylation sites were successfully obtained in response to VAP and SAHA treatment. It is found that VPA and SAHA treatment differently induced proteome and acetylome profiling in AML HL60 cells. This study revealed the differential impacts of VPA and SAHA on proteome/acetylome in AML cells, deepening our understanding of HDAC inhibitor mediated AML therapeutics. PMID- 26822727 TI - Brain Region-Specific Degeneration with Disease Progression in Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2 Disease). AB - BACKGROUND AND PURPOSE: Late infantile neuronal ceroid lipofuscinosis (CLN2 disease) is a uniformly fatal lysosomal storage disease resulting from mutations in the CLN2 gene. Our hypothesis was that regional analysis of cortical brain degeneration may identify brain regions that are affected earliest and most severely by the disease. MATERIALS AND METHODS: Fifty-two high-resolution 3T MR imaging datasets were prospectively acquired on 38 subjects with CLN2. A retrospective cohort of 52 disease-free children served as a control population. The FreeSurfer software suite was used for calculation of cortical thickness. RESULTS: An increased rate of global cortical thinning in CLN2 versus control subjects was the primary finding in this study. Three distinct patterns were observed across brain regions. In the first, subjects with CLN2 exhibited differing rates of cortical thinning versus age. This was true in 22 and 26 of 34 regions in the left and right hemispheres, respectively, and was also clearly discernable when considering brain lobes as a whole and Brodmann regions. The second pattern exhibited a difference in thickness from healthy controls but with no discernable change with age (9 left hemispheres, 5 right hemispheres). In the third pattern, there was no difference in either the rate of cortical thinning or the mean cortical thickness between groups (3 left hemispheres, 3 right hemispheres). CONCLUSIONS: This study demonstrates that CLN2 causes differential rates of degeneration across the brain. Anatomic and functional regions that degenerate sooner and more severely than others compared with those in healthy controls may offer targets for directed therapies. The information gained may also provide neurobiologic insights regarding the mechanisms underlying disease progression. PMID- 26822729 TI - Clinical Impact of Ventilation Duration in Patients with Stroke Undergoing Interventional Treatment under General Anesthesia: The Shorter the Better? AB - BACKGROUND AND PURPOSE: Whether general anesthesia for neurothrombectomy in patients with ischemic stroke has a negative impact on clinical outcome is currently under discussion. We investigated the impact of early extubation and ventilation duration in a cohort that underwent thrombectomy under general anesthesia. MATERIALS AND METHODS: We analyzed 103 consecutive patients from a prospective stroke registry. They met the following criteria: CTA-proved large vessel occlusion in the anterior circulation, ASPECTS above 6 on presenting cranial CT, revascularization by thrombectomy with the patient under general anesthesia within 6 hours after onset of symptoms, and available functional outcome (mRS) 90 days after onset. RESULTS: The mean ventilation time was 128.07 +/- 265.51 hours (median, 18.5 hours; range, 1-1244.7 hours). Prolonged ventilation was associated with pneumonia during hospitalization and unfavorable functional outcome (mRS >=3) and death at follow-up (Mann-Whitney U test; P <= .001). According to receiver operating characteristic analysis, a cutoff after 24 hours predicted unfavorable functional outcome with a sensitivity and specificity of 60% and 78%, respectively. Our results imply that delayed extubation was not associated with a less favorable clinical outcome compared with immediate extubation after the procedure. CONCLUSIONS: Short ventilation times are associated with a lower pneumonia rate and more favorable clinical outcome. Cautious interpretation of our data implies that whether patients are extubated immediately after the procedure is irrelevant for clinical outcome as long as ventilation does not exceed 24 hours. PMID- 26822728 TI - Lateral Asymmetry and Spatial Difference of Iron Deposition in the Substantia Nigra of Patients with Parkinson Disease Measured with Quantitative Susceptibility Mapping. AB - BACKGROUND AND PURPOSE: Quantitative susceptibility mapping is useful for assessing iron deposition in the substantia nigra of patients with Parkinson disease. We aimed to determine whether quantitative susceptibility mapping is useful for assessing the lateral asymmetry and spatial difference in iron deposits in the substantia nigra of patients with Parkinson disease. MATERIALS AND METHODS: Our study population comprised 24 patients with Parkinson disease and 24 age- and sex-matched healthy controls. They underwent 3T MR imaging by using a 3D multiecho gradient-echo sequence. On reconstructed quantitative susceptibility mapping, we measured the susceptibility values in the anterior, middle, and posterior parts of the substantia nigra, the whole substantia nigra, and other deep gray matter structures in both hemibrains. To identify the more and less affected hemibrains in patients with Parkinson disease, we assessed the severity of movement symptoms for each hemibrain by using the Unified Parkinson's Disease Rating Scale. RESULTS: In the posterior substantia nigra of patients with Parkinson disease, the mean susceptibility value was significantly higher in the more than the less affected hemibrain substantia nigra (P < .05). This value was significantly higher in both the more and less affected hemibrains of patients with Parkinson disease than in controls (P < .05). Asymmetry of the mean susceptibility values was significantly greater for patients than controls (P < .05). Receiver operating characteristic analysis showed that quantitative susceptibility mapping of the posterior substantia nigra in the more affected hemibrain provided the highest power for discriminating patients with Parkinson disease from the controls. CONCLUSIONS: Quantitative susceptibility mapping is useful for assessing the lateral asymmetry and spatial difference of iron deposition in the substantia nigra of patients with Parkinson disease. PMID- 26822730 TI - ICD-10: History and Context. AB - In recent months, organized medicine has been consumed by the anticipated transition to the 10th iteration of the International Classification of Disease system. Implementation has come and gone without the disruptive effects predicted by many. Despite the fundamental role the International Classification of Disease system plays in health care delivery and payment policy, few neuroradiologists are familiar with the history of its implementation and implications beyond coding for diseases. PMID- 26822731 TI - Same-Day Sinus and Brain CT Imaging in the Medicare Population: Are Practice Patterns Changing in Association with Medicare Policy Initiatives? AB - BACKGROUND AND PURPOSE: Monitoring the frequency of same-day sinus and brain CT (Outpatient Measure 14, "OP-14") is part of a recent large Centers for Medicare and Medicaid Services hospital outpatient quality initiative to improve imaging efficiency. This study investigates patient-level claims data in the Medicare population focusing on where same-day sinus and brain CT imaging is performed and how the frequency of same-day studies changed with time before and during OP-14 measure program implementation. MATERIALS AND METHODS: Research Identifiable Files were used to identify all sinus and brain CT examinations from 2004 through 2012 for a 5% random patient sample of Medicare fee-for-service beneficiaries. Overall and site of service use rates were calculated for same- and non-same-day examinations. Changes were mapped to policy initiative timetables. RESULTS: The number of same-day sinus and brain CT studies from 2004 to 2012 increased 67% from 1.85 (95% CI, 1.78-1.91) per 1000 Medicare beneficiaries in 2004 to 3.08 (95% CI, 3.00-3.15) in 2012. The biggest driver of increased same-day studies was the emergency department setting, from 0.56 (95% CI, 0.53-0.60) per 1000 to 1.78 (95% CI, 1.72-1.84; +215.7%). Overall use of brain CT from 146.0 (95% CI, 145.1 146.9) per 1000 to 176.3 (95% CI, 175.4-177.2; +21%) and sinus CT from 12.6 (95% CI, 12.4-12.8) per 1000 to 15.4 (95% CI, 15.2-15.6; +22%) increased until 2009 and remained stable through 2012. CONCLUSIONS: Previously increasing same-day sinus and brain CT in Medicare beneficiaries plateaued in 2009, coinciding with the implementation of targeted measures by the Centers for Medicare and Medicaid Services. Same-day imaging continues to increase in the emergency department setting. PMID- 26822732 TI - Reply. PMID- 26822733 TI - Prospective audit of a dedicated ear, nose and throat emergency department and 24 year comparison. AB - BACKGROUND: The Royal Victoria Eye and Ear Hospital provides a specialised ear, nose and throat (ENT) Emergency department (ED) service open to patients from the entire country, operating from 9 am to 5 pm on weekdays. Recently, this has been under threat of closure. AIMS: We analyse and determine the role of this ED in the current context and compare results to a previous study from June 1990. METHODS: A prospective study over a 1-month period (March 2014) was conducted. A questionnaire was used, adapted from the study in 1990. RESULTS: Comparative figures from June 1990 are in parentheses. During the study period, there were 945 (1167) consultations from 887 (779) patients. 57 % (45 %) were new patients and 43 % (55 %) were return patients. Repeat attendances were necessary in 54 (325) patients during this month. 56 % (35 %) were referred by their General Practitioner (GP), 38 % (52 %) self-referred, 2 % (8 %) by other hospitals and 4 % (5 %) from other sources. Diagnoses included otitis externa in 24 % (21 %), cerumen in 20 % (15 %), epistaxis in 6 % (9 %), Eustachian tube dysfunction in 12 %, foreign body removal in 4 % (5 %) and four new cases of head and neck cancer. Attendance numbers vary during the year but demand has risen over time. CONCLUSIONS: A dedicated ED provides an important role for ENT in Ireland and offers valuable experience for trainees. The loss of such a department may lead to an overwhelming burden on services in other hospitals. PMID- 26822734 TI - 'I don't view myself as a woman politician, I view myself as a politician who's a woman': The discursive management of gender identity in political leadership. AB - Former Prime Minister Julia Gillard's speech in the Australian parliament on sexism and misogyny received considerable public attention and controversy. However, less attention has been paid to how Gillard attended and oriented to issues related to her status as a woman during the period between her elevation to the position of Prime Minister in June 2010 and the delivery of the misogyny speech in October 2012. Using a discursive psychological approach, this article examines a corpus of interview transcripts in which gender was occasioned both explicitly and implicitly by speakers, thus requiring Gillard to attend to her gender identity. The analysis demonstrates that far from making gender a salient and relevant membership category, Gillard worked strategically to mitigate her gender as merely inconsequential to her role as Prime Minister. These findings are discussed in relation to existing research examining how gender is oriented to, negotiated, and resisted in talk to accomplish social actions, and more specifically what may be at stake for women in leadership positions who explicitly orient to gender as an identity category. PMID- 26822735 TI - Enolase, a plasminogen receptor isolated from salivary gland transcriptome of the ixodid tick Haemaphysalis flava. AB - Enolase, a multifunctional protein, is shown to act as a plasminogen receptor that contributes to fibrinolysis, which plays an important role in preventing the formation of blood clots during tick feeding. The study of enolase genes provides opportunities to develop a potential antigen target for tick control. So far, enolase has been identified in only a few species of ticks. Knowledge of the exact mechanisms of plasminogen activation and fibrinolysis by enolase as a plasminogen receptor is limited. Here, we cloned the enolase full-length complementary DNA (cDNA) from the salivary glands of Haemaphysalis flava, expressed it, and analyzed the function of the recombinant H. flava enolase. The enolase cDNA was 1988 bp in length and encoded 433 amino acid residues. It contained two domains and some highly conserved functional motifs including an assumed membrane re-association region "AAVPSGASTGI." The enolase exhibited 83.3 % amino acid similarity to that of the putative enolase of Ixodes ricinus, and 85 % to that of Ornithodoros moubata enolase. After eukaryotic expression in insect cells, Western blot analysis showed that the mouse antiserum against the hexahistidine-tagged recombinant enolase protein recognized a band of approximately 48 kDa. The recombinant enolase bound human plasminogen in a dose dependent manner and enhanced plasminogen activation in the presence of host tissue plasminogen activator (t-PA), most probably to promote fibrinolysis and maintain blood flow at the host-tick interface. Real-time quantitative polymerase chain reaction (qPCR) analysis showed that the expression level of enolase in salivary glands was significantly higher than in other tested tissues. Although the enolase was expressed in all developmental stages, it had the highest expression in the rapid blood feeding period of ticks. These findings indicate that the enolase might play an important role in blood feeding of H. flava. PMID- 26822736 TI - Morphological and molecular genetic characterization of two Kudoa spp., K. musculoliquefaciens, and K. pleurogrammi n. sp. (Myxosporea: Multivalvulida), causing myoliquefaction of commercial marine fish. AB - Genetic characterization of myxosporean species, including members of the genus Kudoa, has advanced dramatically throughout the last decade. This is in stark contrast to those species described further back in time. Kudoa musculoliquefaciens described from the jellied muscle of swordfish, Xiphias gladius, in the western Pacific Ocean off the Sanriku Coast, northern Japan, is one such species. In the present study, multiple pseudocysts (0.66-1.35 mm average length and 0.06-0.10 mm average width) containing K. musculoliquefaciens spores were collected from three host groups: muscle blocks of swordfish caught in the western Pacific Ocean off the Sanriku Coast, or the northern Indian Ocean, and Indo-Pacific sailfish, Istiophorus platypterus, in the western Pacific Ocean off Kochi, western Japan. Subspherical K. musculoliquefaciens spores, 8.0-10.3 MUm in width, 7.3-10.0 MUm in thickness, 6.4-7.9 MUm in sutural thickness, and 5.5-8.1 MUm in length, had four subspherical polar capsules, 2.8-4.0 MUm in length by 2.2-3.2 MUm in width. The kudoid spores found in the different host groups showed morphometric variations to some extent but had essentially identical nucleotide sequences of the ribosomal RNA gene (rDNA), closest to those of Kudoa hemiscylli or Kudoa carcharhini recorded from elasmobranchs in the Indo Pacific Ocean. Another kudoid species, Kudoa pleurogrammi n. sp., was recorded from the jellied and normal muscles of Atka mackerel, Pleurogrammus monopterygius and Pleurogrammus azonus, fished in the northern Pacific Ocean or northern Sea of Japan. Subquadrate spores found in round-ended pseudocysts (1.15-3.85 mm in length and 0.11-0.26 mm in width) in myofibers were 8.2-9.1 MUm in width, 7.1-8.2 MUm in thickness, 5.4-7.7 MUm in sutural thickness, and 5.6-6.8 MUm in length, with four ovoid polar capsules, 2.7-2.9 MUm in length by 1.4-2.0 MUm in width. Kudoid spores from both jellied and normal muscles or different host fish species had identical 18S or 28S rDNA nucleotide sequences. Thus, molecular genetic characterization of kudoid species with the potential to induce post-mortem myoliquefaction will facilitate the reliable and specific identification of myxosporeans found in either jellied or normal muscles of important commercial fish. PMID- 26822737 TI - Predicting emerging care-need with simple functional indicators: Findings from a national cohort study in Taiwan. AB - AIM: To evaluate the predictive abilities of single items and their combinations in the instrumental activities of daily living and Nagi scales to predict emerging care-need of older adults. METHODS: We analyzed the 1999 (baseline) and 2003 (end-point) datasets of the Taiwan Longitudinal Study on Aging. After excluding the proxy respondents, incomplete data or those who had care-need at baseline, 2521 of the 2890 participants (aged >=65 years at baseline) were included in data analysis. Care-need was defined as a person receiving formal or informal care, or having any activities of daily living dependency. The predictive abilities of the items in instrumental activities of daily living or Nagi scale, singly or in combination to predict emerging care-need during the subsequent 4 years were evaluated by the improvement in values of Nagelkerke R2 , Akaike information criterion and Bayesian information criterion in logistic regression models. RESULTS: The single item "doing heavy housework" showed the best predictive abilities among all others. When combined this item with "walking 200 m," the two-item indicator significantly improved the predictive abilities. However, no three-item combined indicator improved the predictive abilities. CONCLUSIONS: The two-item indicator that combines "doing heavy housework" and "walking 200 m" from the instrumental activities of daily living and Nagi scales showed superior ability to predict emerging care-need of older Taiwanese. The indicator could serve as the foundation for developing a scale to predict emerging care-need of older adults. Geriatr Gerontol Int 2017; 17: 375-381. PMID- 26822738 TI - Drug-resistant tuberculosis control in China: progress and challenges. AB - BACKGROUND: China has the second highest caseload of multidrug-resistant tuberculosis (MDR-TB) in the world. In 2009, the Chinese government agreed to draw up a plan for MDR-TB prevention and control in the context of a comprehensive health system reform launched in the same year. DISCUSSION: China is facing high prevalence rates of drug-resistant TB and MDR-TB. MDR-TB disproportionally affects the poor rural population and the highest rates are in less developed regions largely due to interrupted and/or inappropriate TB treatment. Most households with an affected member suffer a heavy financial burden because of a combination of treatment and other related costs. The influential Global Fund programme for MDR-TB control in China provides technical and financial support for MDR-TB diagnosis and treatment. However, this programme has a fixed timeline and cannot provide a long term solution. In 2009, the Bill and Melinda Gates Foundation, in cooperation with the National Health and Family Planning Commission of China, started to develop innovative approaches to TB/MDR TB management and case-based payment mechanisms for treatment, alongside increased health insurance benefits for patients, in order to contain medical costs and reduce financial barriers to treatment. Although these efforts appear to be in the right direction, they may not be sufficient unless (a) domestic sources are mobilized to raise funding for TB/MDR-TB prevention and control and (b) appropriate incentives are given to both health facilities and their care providers. Along with the on-going Chinese health system reform, sustained government financing and social health protection schemes will be critical to ensure universal access to appropriate TB treatment in order to reduce risk of developing MDR-TB and systematic MDR-TB treatment and management. PMID- 26822739 TI - Factors Determining the Choice of Surgical Procedure in Elderly Patients with Non Small Cell Lung Cancer. AB - BACKGROUND: In the elderly patients, optimal surgical treatment can be difficult to achieve, because of comorbidity. Therefore, we aimed to clarify the preferred surgical management in this patient group. METHODS: A retrospective study was conducted between April 2008 and March 2015 that included patients with non-small cell lung cancer (NSCLC) aged >= 75 years. RESULTS: We included 44 patients who underwent partial resection (n = 20) or lobectomy (n = 24). There were no significant differences between the two groups on most variables, except for some character. Survival analysis revealed a significant difference in overall survival (OS) between the two groups; however, no significant differences existed in the disease-free survival or in the OS for stage I disease. Postoperative complications led to poor prognoses. Cox regression analysis revealed statistical significance for the Brinkman Index, the ratio of the pulmonary artery diameter to the ascending aorta diameter (PA:A), and the alveolar-arterial oxygen gradient. Only the PA:A ratio remained significant after multivariate analysis, with a higher ratio associated with better survival. CONCLUSION: In elderly patients with NSCLC, surgical resection should not be denied because of age alone. However, partial resection should be favored to lobectomy when possible. PMID- 26822740 TI - New digital cholangiopancreatoscopy for diagnosis and therapy of pancreaticobiliary diseases (with videos). AB - BACKGROUND: Recently, a new digital cholangiopancreatoscopy (DCPS) has been developed. The aim of this study is to retrospectively evaluate the utility of new DCPS in patients with pancreaticobiliary diseases. METHODS: Digital cholangiopancreatoscopy was used in 26 patients (16 men) with pancreaticobiliary diseases that could not be diagnosed and treated by standard endoscopic retrograde cholangiopancreatography (ERCP). The procedures included DCPS-guided tissue sampling and interventions. Technical success and adverse events were evaluated. RESULTS: Among the 26 patients, 19 patients were classified for diagnostic purposes and seven for therapeutic purposes. The detailed breakdown of the particular conditions and numbers of patients was as follows: indeterminate bile duct (BD) lesion, indeterminate pancreatic duct (PD) lesion, lithotripsy by yttrium aluminum garnet-laser or electrohydraulic lithotripsy, removal of migrated BD stent and PD stent, and guidewire passing across the biliary stricture. The overall technical success rates of visualizing the target lesions and therapeutic interventions were 100% and 85.7%, respectively. The incidence of procedure-related adverse events among the patients was 7.7% (2/26). Cholangitis developed in one of the patients and post-endoscopic sphincterotomy bleeding in one patient. All adverse events were successfully treated by conservative therapy. CONCLUSION: Digital cholangiopancreatoscopy has a high potential for providing an accurate diagnosis and facilitating therapy in patients with pancreaticobiliary diseases. PMID- 26822741 TI - Submental Orotracheal Intubation-A Technique for Airway Management in Severe Facial Trauma. PMID- 26822742 TI - Mesenchymal stem cell therapy in treatment of erectile dysfunction: Autologous or allogeneic cell sources? PMID- 26822743 TI - Phenytoin in acute optic neuritis: neuroprotective or not? PMID- 26822744 TI - Vocal tics in Tourette's syndrome. PMID- 26822745 TI - Energy balance: yet another challenge for neurodegenerative diseases. PMID- 26822747 TI - Refining diagnosis of multiple sclerosis with revised MRI criteria. PMID- 26822746 TI - MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. AB - In patients presenting with a clinically isolated syndrome, MRI can support and substitute clinical information in the diagnosis of multiple sclerosis by showing disease dissemination in space and time and by helping to exclude disorders that can mimic multiple sclerosis. MRI criteria were first included in the diagnostic work-up for multiple sclerosis in 2001, and since then several modifications to the criteria have been proposed in an attempt to simplify lesion-count models for showing disease dissemination in space, change the timing of MRI scanning to show dissemination in time, and increase the value of spinal cord imaging. Since the last update of these criteria, new data on the use of MRI to establish dissemination in space and time have become available, and MRI technology has improved. State-of-the-art MRI findings in these patients were discussed in a MAGNIMS workshop, the goal of which was to provide an evidence-based and expert opinion consensus on proposed modifications to MRI criteria for the diagnosis of multiple sclerosis. PMID- 26822748 TI - Amyotrophic lateral sclerosis and frontotemporal dementia: distinct and overlapping changes in eating behaviour and metabolism. AB - Metabolic changes incorporating fluctuations in weight, insulin resistance, and cholesterol concentrations have been identified in several neurodegenerative disorders. Whether these changes result from the neurodegenerative process affecting brain regions necessary for metabolic regulation or whether they drive the degenerative process is unknown. Emerging evidence from epidemiological, clinical, pathological, and experimental studies emphasises a range of changes in eating behaviours and metabolism in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In ALS, metabolic changes have been linked to disease progression and prognosis. Furthermore, changes in eating behaviour that affect metabolism have been incorporated into the diagnostic criteria for FTD, which has some clinical and pathological overlap with ALS. Whether the distinct and shared metabolic and eating changes represent a component of the proposed spectrum of the two diseases is an intriguing possibility. Moreover, future research should aim to unravel the complex connections between eating, metabolism, and neurodegeneration in ALS and FTD, and aim to understand the potential for targeting modifiable risk factors in disease development and progression. PMID- 26822749 TI - Phenytoin for neuroprotection in patients with acute optic neuritis: a randomised, placebo-controlled, phase 2 trial. AB - BACKGROUND: Acute demyelinating optic neuritis, a common feature of multiple sclerosis, can damage vision through neurodegeneration in the optic nerve and in its fibres in the retina. Inhibition of voltage-gated sodium channels is neuroprotective in preclinical models. In this study we aimed to establish whether sodium-channel inhibition with phenytoin is neuroprotective in patient with acute optic neuritis. METHODS: We did a randomised, placebo-controlled, double-blind phase 2 trial at two UK academic hospitals in London and Sheffield. Patients with acute optic neuritis aged 18-60 years, presenting within 2 weeks of onset, with visual acuity of 6/9 or worse, were randomly assigned (1:1) by minimisation via a web-based service to oral phenytoin (maintenance dose 4 mg/kg per day if randomised before or on July 16, 2013, and 6 mg/kg per day if randomised on or after July 17, 2013) or placebo for 3 months, stratified by time from onset, centre, previous multiple sclerosis diagnosis, use of disease modifying treatment, and use of corticosteroids for acute optic neuritis. Participants and treating and assessing physicians were masked to group assignment. The primary outcome was retinal nerve fibre layer (RNFL) thickness in the affected eye at 6 months, adjusted for fellow-eye RNFL thickness at baseline, analysed in a modified intention-to-treat population of all randomised participants who were followed up at 6 months. Safety was analysed in the entire population, including those who were lost to follow-up. The trial is registered with ClinicalTrials.gov, number NCT 01451593. FINDINGS: We recruited 86 participants between Feb 3, 2012, and May 22, 2014 (42 assigned to phenytoin and 44 to placebo). 29 were assigned to phenytoin 4 mg/kg and 13 to phenytoin 6 mg/kg. Five participants were lost to follow-up, so the primary analysis included 81 participants (39 assigned to phenytoin and 42 to placebo). Mean 6-month RNFL thickness in the affected eye at 6 months was 81.46 MUm (SD 16.27) in the phenytoin group (a mean decrease of 16.69 MUm [SD 13.73] from baseline) versus 74.29 MUm (15.14) in the placebo group (a mean decrease of 23.79 MUm [13.97] since baseline; adjusted 6-month difference of 7.15 MUm [95% CI 1.08-13.22]; p=0.021), corresponding to a 30% reduction in the extent of RNFL loss with phenytoin compared with placebo. Treatment was well tolerated, with five (12%) of 42 patients having a serious adverse event in the phenytoin group (only one, severe rash, was attributable to phenytoin) compared with two (5%) of 44 in the placebo group. INTERPRETATION: These findings support the concept of neuroprotection with phenytoin in patients with acute optic neuritis at concentrations at which it blocks voltage-gated sodium channels selectively. Further investigation in larger clinical trials in optic neuritis and in relapsing multiple sclerosis is warranted. FUNDING: US National Multiple Sclerosis Society, Multiple Sclerosis Society of Great Britain and Northern Ireland, Novartis, UK National Institute for Health Research (NIHR), and NIHR UCLH/UCL Biomedical Research Centre. PMID- 26822750 TI - HSMNR belongs to the most frequent types of hereditary neuropathy in the Czech Republic and is twice more frequent than HMSNL. AB - Hereditary motor and sensory neuropathy type Russe (HMSNR), also called CMT4G, is an autosomal recessive inherited peripheral neuropathy (IPN) caused by a founder mutation in the HK1 gene. HMSNR affects only patients with Roma origin, similar to the better known HMSN type Lom clarified earlier. By testing IPN patients with Roma origin, we realized that HMSNR affects surprisingly many patients in the Czech Republic. HMSNR is one of the most frequent types of IPN in this country and appears to be twice more frequent than HMSNL. Pronounced lower limb atrophies and severe deformities often lead to walking inability in even young patients, but hands are usually only mildly affected even after many years of disease duration. The group of 20 patients with HMSNR presented here is the first report about the prevalence of HMSNR from central Europe. PMID- 26822751 TI - Identifying Fundamental Limitations in Halide Perovskite Solar Cells. AB - The temperature dependence of the principal photovoltaic parameters of perovskite photovoltaics is studied. The recombination activation energy is in good agreement with the perovskite's bandgap energy, thereby placing an upper bound on the open-circuit voltage. The photocurrent increases moderately with temperature and remains high at low temperature, reinforcing that the cells are not hindered by insufficient thermally activated mobility or carrier trapping by deep defects. PMID- 26822752 TI - PD-1 Pathway Inhibitors: Immuno-Oncology Agents for Restoring Antitumor Immune Responses. AB - Immune checkpoint inhibitors are designed to restore a patient's own antitumor immune response that has been suppressed during tumor development. The first monoclonal antibodies against the immune checkpoint programmed death 1 (PD-1) receptor, nivolumab and pembrolizumab, are now approved for clinical use. Both agents are indicated for the treatment of advanced melanoma, as well as for the treatment of metastatic non-small cell lung cancer (NSCLC). Nivolumab is also approved for the treatment of advanced renal cell carcinoma. In patients with melanoma, these agents result in objective response rates of ~25-40%, with durable responses lasting more than 2 years in some cases. Results from phase III trials have shown improved survival with nivolumab versus standard-of-care chemotherapy in both patients with advanced melanoma and those with advanced NSCLC. In patients with advanced melanoma, both PD-1 inhibitors (nivolumab and pembrolizumab) have shown improved survival versus ipilimumab. PD-1 inhibitors are associated with adverse events that have immune etiologies, with grade greater than 3 adverse events typically reported in 16% or less of patients. However, most immune-mediated adverse events (including grade 3-4 adverse events) can be managed by using published management algorithms without permanent discontinuation of the agent. As nivolumab and pembrolizumab enter the clinic, and with more PD-1 pathway agents in development for a range of tumor types, this review aims to provide pharmacists with a basic understanding of the role of PD-1 in modulating the immune system and their use in the cancer treatment. The most recent clinical efficacy and safety data are discussed, highlighting the response characteristics distinctive to immune checkpoint inhibitors, along with pharmacokinetic and pharmacodynamic data and cost considerations. PMID- 26822753 TI - Post-Procedural Bivalirudin Infusion Following Primary PCI to Reduce Stent Thrombosis. AB - BACKGROUND: Prolonging infusions may abrogate the acute stent thrombosis (ST) associated with bivalirudin use during primary PCI but at an increased cost. We hypothesized that continuing the bivalirudin infusion commenced during the procedure at the PCI recommended dose until infusion end would prevent excess early ST. METHODS: Baseline demographics, procedural data and outcomes were gathered prospectively on 1395 consecutive patients undergoing primary PCI. The choice of bivalirudin versus heparin was at the cardiologist's discretion. Local protocol recommended continuation of the procedural bivalirudin at the PCI dose until infusion end. RESULTS: Patients' mean age was 62.8 +/- 13.1years with 11.4% presenting with shock. The majority of patients underwent PCI using bivalirudin with fewer using heparin (87.7 vs. 12.3%, P < 0.0001). Glycoprotein inhibitor bailout rates were 6.1% with bivalirudin and 36.3% with heparin (P < 0.0001). Calculated on an individual patient basis the median intra-procedure duration of the bivalirudin infusion was 30(IQR 21-43) minutes and post-procedure 49(32-66) minutes. The acute (<24-hours) ST rates were 4/1224 with bivalirudin +/- GPI (0.3%) and 0/171 with heparin +/- GPI (0%, P = 0.41). The sub-acute (24-hours to 30-days) ST rates were 3/1224 for bivalirudin +/- GPI (0.3%) and 2/171 with heparin +/- GPI (1.2%, P = 0.11). In total the early (<30-days) ST rates were 7/1224 for bivalirudin +/- GPI (0.6%) and 2/171 with heparin +/- GPI (1.2%, P = 0.31). Acute ST was significantly more likely to occur in clopidogrel-loaded patients than prasugrel/ticagrelor patients (2.7 vs. 0.5%, P = 0.003). CONCLUSION: Continuing the bivalirudin infusion commenced during the procedure at the PCI recommended dose until infusion end combined with potent P2 Y12 inhibitors ameliorates excess early stent thrombosis. PMID- 26822754 TI - Modernization of Test Methods for the Analysis of Infant Formula and Adult Nutritionals. PMID- 26822755 TI - Testing monophyly of the freshwater fish Leporinus (Characiformes, Anostomidae) through molecular analysis. AB - Monophyly of the genus Leporinus (Characiformes: Anostomidae) was tested by sequencing and analysing a total of 4732 bp, including two mitochondrial [cytochrome oxidase subunit 1 (CO1) and cytochrome b (Cytb)] and three nuclear [myosin heavy chain 6 cardiac muscle alpha (Myh6), recombination activating gene 1 (RAG1) and recombination activating gene 2 (RAG2)] loci for 22 species of Leporinus, or c. 25% of all described species in the genus. Phylogenetic tree analyses (maximum parsimony, maximum likelihood and Bayesian species tree) indicate Leporinus to be paraphyletic, with monophyly being rejected by both Kishino-Hasegawa and Shimodaira-Hasegawa tests. The sequenced species of Leporinus are distributed across five clades that are interleaved among other anostomid genera. Several taxonomic changes are suggested as being necessary to restore monophyly for the group. The clade containing the type species, Leporinus fasciatus, should be considered Leporinus sensu stricto and at least three new genera should be described for other species currently considered part of Leporinus. PMID- 26822756 TI - Enzyme Selectivity Fine-Tuned through Dynamic Control of a Loop. AB - Allostery has been revealed as an essential property of all proteins. For enzymes, shifting of the structural equilibrium distribution at one site can have substantial impacts on protein dynamics and selectivity. Promising sites of remotely shifting such a distribution by changing the dynamics would be at flexible loops because relatively large changes may be achieved with minimal modification of the protein. A ligand-selective change of binding affinity to the active site of cyclophilin is presented involving tuning of the dynamics of a highly flexible loop. Binding affinity is increased upon substitution of double Gly to Ala at the hinge regions of the loop. Quenching of the motional amplitudes of the loop slightly rearranges the active site. In particular, key residues for binding Phe60 and His126 adopt a more fixed orientation in the bound protein. Our system may serve as a model system for studying the effects of various time scales of loop motion on protein function tuned by mutations. PMID- 26822758 TI - Pure-quartic solitons. AB - Temporal optical solitons have been the subject of intense research due to their intriguing physics and applications in ultrafast optics and supercontinuum generation. Conventional bright optical solitons result from the interaction of anomalous group-velocity dispersion and self-phase modulation. Here we experimentally demonstrate a class of bright soliton arising purely from the interaction of negative fourth-order dispersion and self-phase modulation, which can occur even for normal group-velocity dispersion. We provide experimental and numerical evidence of shape-preserving propagation and flat temporal phase for the fundamental pure-quartic soliton and periodically modulated propagation for the higher-order pure-quartic solitons. We derive the approximate shape of the fundamental pure-quartic soliton and discover that is surprisingly Gaussian, exhibiting excellent agreement with our experimental observations. Our discovery, enabled by precise dispersion engineering, could find applications in communications, frequency combs and ultrafast lasers. PMID- 26822757 TI - Zebrafish and Medaka: new model organisms for modern biomedical research. AB - Although they are primitive vertebrates, zebrafish (Danio rerio) and medaka (Oryzias latipes) have surpassed other animals as the most used model organisms based on their many advantages. Studies on gene expression patterns, regulatory cis-elements identification, and gene functions can be facilitated by using zebrafish embryos via a number of techniques, including transgenesis, in vivo transient assay, overexpression by injection of mRNAs, knockdown by injection of morpholino oligonucleotides, knockout and gene editing by CRISPR/Cas9 system and mutagenesis. In addition, transgenic lines of model fish harboring a tissue specific reporter have become a powerful tool for the study of biological sciences, since it is possible to visualize the dynamic expression of a specific gene in the transparent embryos. In particular, some transgenic fish lines and mutants display defective phenotypes similar to those of human diseases. Therefore, a wide variety of fish model not only sheds light on the molecular mechanisms underlying disease pathogenesis in vivo but also provides a living platform for high-throughput screening of drug candidates. Interestingly, transgenic model fish lines can also be applied as biosensors to detect environmental pollutants, and even as pet fish to display beautiful fluorescent colors. Therefore, transgenic model fish possess a broad spectrum of applications in modern biomedical research, as exampled in the following review. PMID- 26822759 TI - Synthesis of vinyl-terminated Au nanoprisms and nanooctahedra mediated by 3 butenoic acid: direct Au@pNIPAM fabrication with improved SERS capabilities. AB - Here we describe the first seedless synthesis of vinyl-terminated Au nanotriangular prisms (AuNTPs) and nanooctahedra (AuNOC) in aqueous media. This synthesis is performed by chemical reduction of chloroauric acid (HAuCl4) with 3 butenoic acid (3BA) in the presence of benzyldimethylammonium chloride (BDAC). The principal novelties of the presented method are the use of a mixture of 3BA and BDAC, the synthesis of gold prisms and octahedra with controllable size, and the presence of terminal double bonds on the metal surface. Initially this method produces a mixture of triangular gold nanoprisms and octahedra; however, both morphologies are successfully separated by surfactant micelle induced depletion interaction, reaching percentages up to ~90%. Moreover, the alkene moieties present on the gold surface are exploited for the fabrication of hybrid core@shell particles. Gold octahedra and triangular prisms are easily encapsulated by free radical polymerization of N-isopropylacrylamide (NIPAM). Finally, in order to obtain a gold core with the most number of tips, AuNTP@pNIPAM microgels were subjected to gold core overgrowth, thus resulting in star-shaped nanoparticles (AuSTs@pNIPAM). We use 4-amino-benzenethiol as the model analyte for SERS investigations. As expected, gold cores with tips and high curvature sites produced the highest plasmonic responses. PMID- 26822760 TI - Automated imaging technologies for the diagnosis of glaucoma: a comparative diagnostic study for the evaluation of the diagnostic accuracy, performance as triage tests and cost-effectiveness (GATE study). AB - BACKGROUND: Many glaucoma referrals from the community to hospital eye services are unnecessary. Imaging technologies can potentially be useful to triage this population. OBJECTIVES: To assess the diagnostic performance and cost effectiveness of imaging technologies as triage tests for identifying people with glaucoma. DESIGN: Within-patient comparative diagnostic accuracy study. Markov economic model comparing the cost-effectiveness of a triage test with usual care. SETTING: Secondary care. PARTICIPANTS: Adults referred from the community to hospital eye services for possible glaucoma. INTERVENTIONS: Heidelberg Retinal Tomography (HRT), including two diagnostic algorithms, glaucoma probability score (HRT-GPS) and Moorfields regression analysis (HRT-MRA); scanning laser polarimetry [glaucoma diagnostics (GDx)]; and optical coherence tomography (OCT). The reference standard was clinical examination by a consultant ophthalmologist with glaucoma expertise including visual field testing and intraocular pressure (IOP) measurement. MAIN OUTCOME MEASURES: (1) Diagnostic performance of imaging, using data from the eye with most severe disease. (2) Composite triage test performance (imaging test, IOP measurement and visual acuity measurement), using data from both eyes, in correctly identifying clinical management decisions, that is 'discharge' or 'do not discharge'. Outcome measures were sensitivity, specificity and incremental cost per quality-adjusted life-year (QALY). RESULTS: Data from 943 of 955 participants were included in the analysis. The average age was 60.5 years (standard deviation 13.8 years) and 51.1% were females. Glaucoma was diagnosed by the clinician in at least one eye in 16.8% of participants; 37.9% of participants were discharged after the first visit. Regarding diagnosing glaucoma, HRT-MRA had the highest sensitivity [87.0%, 95% confidence interval (CI) 80.2% to 92.1%] but the lowest specificity (63.9%, 95% CI 60.2% to 67.4%) and GDx had the lowest sensitivity (35.1%, 95% CI 27.0% to 43.8%) but the highest specificity (97.2%, 95% CI 95.6% to 98.3%). HRT-GPS had sensitivity of 81.5% (95% CI 73.9% to 87.6%) and specificity of 67.7% (95% CI 64.2% to 71.2%) and OCT had sensitivity of 76.9% (95% CI 69.2% to 83.4%) and specificity of 78.5% (95% CI 75.4% to 81.4%). Regarding triage accuracy, triage using HRT-GPS had the highest sensitivity (86.0%, 95% CI 82.8% to 88.7%) but the lowest specificity (39.1%, 95% CI 34.0% to 44.5%), GDx had the lowest sensitivity (64.7%, 95% CI 60.7% to 68.7%) but the highest specificity (53.6%, 95% CI 48.2% to 58.9%). Introducing a composite triage station into the referral pathway to identify appropriate referrals was cost-effective. All triage strategies resulted in a cost reduction compared with standard care (consultant-led diagnosis) but with an associated reduction in effectiveness. GDx was the least costly and least effective strategy. OCT and HRT-GPS were not cost-effective. Compared with GDx, the cost per QALY gained for HRT-MRA is L22,904. The cost per QALY gained with current practice is L156,985 compared with HRT-MRA. Large savings could be made by implementing HRT-MRA but some benefit to patients will be forgone. The results were sensitive to the triage costs. CONCLUSIONS: Automated imaging can be effective to aid glaucoma diagnosis among individuals referred from the community to hospital eye services. A model of care using a triage composite test appears to be cost-effective. FUTURE WORK: There are uncertainties about glaucoma progression under routine care and the cost of providing health care. The acceptability of implementing a triage test needs to be explored. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 26822761 TI - In situ targeting TEM8 via immune response and polypeptide recognition by wavelength-modulated surface plasmon resonance biosensor. AB - There is an increasing interest in real-time and in situ monitoring of living cell activities in life science and medicine. This paper reports a whole cell sensing protocol over the interface of Au film coupled in a wavelength-modulated surface plasmon resonance (WMSPR) biosensor. With dual parabolic mirrors integrated in the sensor, the compact and miniaturized instrument shows satisfactory refractive index sensitivity (2220 nm/RIU) and a high resolution of resonance wavelength shift of 0.3 nm to liquid samples. The affinity interactions between the biomarker of human tumor endothelial marker 8 (TEM8) and antibody (Ab) or specific polypeptide (PEP) were firstly introduced to WMSPR biosensor analysis. Both the interaction events of Ab-cell and PEP-cell over the Au film interface can be recognized by the sensor and the balance time of interactions is about 20 min. The concentration range of Ab for quantitative monitoring of the TEM8 expression on human colon carcinoma SW620 cells was investigated. The present low-cost and time-saving method provides a time resolution of binding specificity between Ab/PEP and TEM8 for real-time analysis of antigen on living tumor cell surface. PMID- 26822762 TI - Digital assessment of preliminary impression accuracy for edentulous jaws: Comparisons of 3-dimensional surfaces between study and working casts. AB - PURPOSE: The aim of this study was to compare 3-dimensional surfaces of study and working casts for edentulous jaws and to evaluate the accuracy of preliminary impressions with a view to the future application of digital dentistry for edentulous jaws. METHODS: Forty edentulous volunteers were serially recruited. Nine dentists took preliminary and final impressions in a routine clinical work up. The study and working casts were digitized using a dental 3-dimensional scanner. The two surface images were superimposed through a least-square algorithm using imaging software and compared qualitatively. Furthermore, the surface of each jaw was divided into 6 sections, and the difference between the 2 images was quantitatively evaluated. RESULTS: Overall inspection showed that the difference around residual ridges was small and that around borders were large. The mean differences in the upper and lower jaws were 0.26mm and 0.45mm, respectively. The maximum values of the differences showed that the upward change mainly occurred in the anterior residual ridge, and the downward change mainly in the posterior border seal, and the labial and buccal vestibules, whereas every border of final impression was shortened in the lower jaw. The accuracy in all areas except the border, which forms the foundation, was estimated to be less than 0.25mm. CONCLUSION: Using digital technology, we here showed the overall and sectional accuracy of the preliminary impression for edentulous jaws. In our clinic, preliminary impressions have been made using an alginate material while ensuring that the requisite impression area was covered. PMID- 26822764 TI - Ethnic Dimensions of Guatemala's Stalled Transition: A Parity-Specific Analysis of Ladino and Indigenous Fertility Regimes. AB - In some contemporary populations, fertility levels appear to plateau, with women maintaining a consistently high level of fertility for a relatively extended period. Because this plateau does not reflect the historical patterns observed in Europe, the focus of most studies on fertility patterns, mechanisms underlying the plateau and the reinstatement of a decline have not been fully explored and are not fully understood. Through the construction of fertility histories of 25,000 women using multiple years of health survey data, we analyze some of the components of stalled fertility as they pertain to Guatemala, the only Central American country to have experienced a stalled fertility decline. PMID- 26822763 TI - Long noncoding RNA NEAT1 promotes laryngeal squamous cell cancer through regulating miR-107/CDK6 pathway. AB - BACKGROUND: Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) plays key role in the progression of some human cancers. However, the role of NEAT1 in human laryngeal squamous cell cancer (LSCC) is still unknown. We therefore investigated the expression and function of NEAT1 in LSCC. METHODS: NEAT1 level in LSCC and adjacent non-neoplastic tissues were detected by qRT-PCR. NEAT1 was knockdown in LSCC cells and cell proliferation, apoptosis and cell cycle were examined. The growth of xenografts with NEAT1 knockdown LSCC cells was analyzed. RESULTS: NEAT1 level was significantly higher in LSCC than in corresponding adjacent non-neoplastic tissues, and patients with neck nodal metastasis or advanced clinical stage had higher NEAT1 expression. Moreover, siRNA mediated NEAT1 knockdown significantly inhibited the proliferation and induced apoptosis and cell cycle arrest at G1 phase in LSCC cells. The growth of LSCC xenografts was significantly suppressed by the injection of NEAT1 siRNA lentivirus. Furthermore, NEAT1 regulated CDK6 expression in LSCC cells which was mediated by miR-107. CONCLUSION: NEAT1 plays an oncogenic role in the tumorigenesis of LSCC and may serve as a potential target for therapeutic intervention. PMID- 26822765 TI - The Largest Metalloid Group 14 Cluster, Ge18[Si(SiMe3)3]6 : An Intermediate on the Way to Elemental Germanium. AB - The oxidation of [Ge9(Hyp)3](-) (Hyp=Si(SiMe3 )3) with an Fe(II) salt leads to Ge18 (Hyp)6 (1), the largest Group 14 metalloid cluster that has been structurally characterized to date. The arrangement of the 18 germanium atoms in 1 shows similarities to that found in the solid-state structure Ge(cF136). Furthermore, 1 can be described as a macropolyhedral cluster of two Ge9 units. Quantum-chemical calculations further hint at a strained arrangement so that 1 can be considered as a first trapped intermediate on the way from Ge9 units to elemental germanium with the clathrate-II structure (Ge(cF136)). PMID- 26822766 TI - Photo Quiz: A 54-Year-Old Male with Acute Myelogenous Leukemia Presenting with Right Periorbital Swelling and Diplopia. PMID- 26822767 TI - Case Reports May Be Declared Dead by the Journal of Clinical Microbiology, but They Are Alive and Well in JMM Case Reports. PMID- 26822768 TI - Reply to "Case Reports May Be Declared Dead by the Journal of Clinical Microbiology, but They Are Alive and Well in JMM Case Reports". PMID- 26822769 TI - Pleural Fluid and Tuberculosis: Are All Interferon Gamma Release Assays Equal? PMID- 26822770 TI - Reply to "Pleural Fluid and Tuberculosis: Are All Interferon Gamma Release Assays Equal?". PMID- 26822771 TI - Correction for Ferreira et al., A Novel Method for Genotyping the Helicobacter pylori vacA Intermediate Region Directly in Gastric Biopsy Specimens. PMID- 26822772 TI - Correction for Aggarwal et al., Interferon Gamma Release Assays for Diagnosis of Pleural Tuberculosis: a Systematic Review and Meta-Analysis. PMID- 26822773 TI - Correction for Humphries and McKinnell, Continuing Challenges for the Clinical Laboratory for Detection of Carbapenem-Resistant Enterobacteriaceae. PMID- 26822776 TI - 'I don't think I'd be frightened if the statins went': a phenomenological qualitative study exploring medicines use in palliative care patients, carers and healthcare professionals. AB - BACKGROUND: There is a growing body of evidence suggesting patients with life limiting illness use medicines inappropriately and unnecessarily. In this context, the perspective of patients, their carers and the healthcare professionals responsible for prescribing and monitoring their medication is important for developing deprescribing strategies. The aim of this study was to explore the lived experience of patients, carers and healthcare professionals in the context of medication use in life-limiting illness. METHODS: In-depth interviews, using a phenomenological approach: methods of transcendental phenomenology were used for the patient and carer interviews, while hermeneutic phenomenology was used for the healthcare professional interviews. RESULTS: The study highlighted that medication formed a significant part of a patient's day-to day routine; this was also apparent for their carers who took on an active role as a gatekeeper of care-in managing medication. Patients described the experience of a point in which, in their disease journey, they placed less importance on taking certain medications; healthcare professionals also recognize this and refer it as a 'transition'. This point appeared to occur when the patient became accepting of their illness and associated life expectancy. There was also willingness by patients, carers and healthcare professionals to review and alter the medication used by patients in the context of life-limiting illness. CONCLUSIONS: There is a need to develop deprescribing strategies for patients with life-limiting illness. Such strategies should seek to establish patient expectations, consider the timing of the discussion about ceasing treatment and encourage the involvement of other stakeholders in the decision-making progress. PMID- 26822777 TI - Early cleavages influence the molecular and the metabolic pattern of individually cultured bovine blastocysts. AB - Embryo morphokinetics suggests that the timing of the first embryonic cell divisions may predict the developmental potential of an embryo; however, correlations between embryonic morphokinetics and physiology are not clear. Here, we used RNA sequencing to determine the gene expression profile of in vitro produced early- and late-dividing bovine embryos and their respective blastocysts, and compared these profiles to in vivo-produced blastocysts to identify differentially expressed genes (DEGs). Principal component analysis revealed that fast- and slow-dividing embryos possess similar transcript abundance over the first cleavages. By the blastocyst stage, however, more DEGs were observed between the fast- and slow-dividing embryo groups, whereas blastocysts from the slow-dividing group were more similar to in vivo-produced blastocysts. Gene ontology enrichment analysis showed that the slow-dividing and in vivo-produced blastocysts shared biological processes related to groups of up- or down-regulated genes when compared to the fast-dividing blastocysts. Based on these DEG results, we characterized the relationship between developmental kinetics and energy metabolism of in vitro-produced bovine embryos. Embryos from fast- and slow-dividing groups exhibited different pyruvate and lactate metabolism at 22 hr post-in vitro culture (hpc), glucose consumption at 96 hpc, and glutamate metabolism at 168 hpc. Glycogen storage was similar between cleavage-stage and morulae groups, but was higher in the blastocysts of the slow dividing group. On the other hand, blastocysts of the fast-dividing group had a higher concentration of lipids. Taken together, these data identify transcriptomic and metabolic differences between embryos with different morphokinetics, suggesting that sorting embryos based on cleavage speed may select for different metabolic patterns. Mol. Reprod. Dev. 83: 324-336, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26822778 TI - Enhanced attention to context: An intervention that increases perceived control in mild depression. AB - People perceive that they have control over events to the extent that the same events do not occur outside of their control, randomly, in the environment or context. Therefore, perceived control should be enhanced if there is a large contrast between one's own control and the control that the context itself seems to exert over events. Given that depression is associated with low perceived control, we tested the hypothesis that enhanced attentional focus to context will increase perceived control in people with and without depression. A total of 106 non-depressed and mildly depressed participants completed a no control zero contingency task with low and high outcome probability conditions. In the experimental context-focus group, participants were instructed to attend to the context, whereas in the control group, participants were instructed to attend to their thoughts. Irrespective of attentional focus, non-depressed participants displayed illusory control. However, people with mild depression responded strongly to the attention focus manipulation. In the control group, they evidenced low perceived control with classic depressive realism effects. In the experimental group, when asked to focus on the context in which events took place, participants with mild depression displayed enhanced perceived control or illusory control, similar to non-depressed participants. Findings are discussed in relation to whether depression effects on perceived control represent tendencies towards realism or attentional aspects of depressive thoughts. PMID- 26822779 TI - Gonadectomy reduces the density of androgen receptor-immunoreactive neurons in male rat's hippocampus: testosterone replacement compensates it. AB - BACKGROUND: In the present study, the role of gonadectomy on memory impairment and the density of androgen receptor-immunoreactive neurons in rats' hippocampus as well as the ability of testosterone to compensate of memory and the density of androgen receptors in the hippocampus was evaluated. METHODS: Adult male rats (except intact-no testosterone group) were bilaterally castrated, and behavioral tests performed 2 weeks later. Animals bilaterally cannulated into lateral ventricles and then received testosterone (10, 40 and 120 ug/0.5 ul DMSO) or vehicle (DMSO; 0.5 ul) for gonadectomized-vehicle group, 30 min before training in water maze test. The androgen receptor-immunoreactive neurons were detected by immunohistochemical technique in the hippocampal areas. RESULTS: In the gonadectomized male rats, a memory deficit was found in Morris water maze test on test day (5th day) after DMSO administration. Gonadectomy decreased density of androgen receptor-immunoreactive neurons in the rats' hippocampus. The treatment with testosterone daily for 5 days attenuated memory deficits induced by gonadectomy. Testosterone also significantly increased the density of androgen receptor-immunoreactive neurons in the hippocampal areas. The intermediate dose of this hormone (40 ug) appeared to have a significant effect on spatial memory and the density of androgen receptor-immunoreactive neurons in gonadectomized rats' hippocampus. CONCLUSIONS: The present study suggests that testosterone can compensate memory failure in gonadectomized rats. Also testosterone replacement can compensate the reduction of androgen receptor-immunoreactive neurons density in the rats' hippocampus after gonadectomy. PMID- 26822780 TI - Parasites as Drivers and Passengers of Human-Mediated Biological Invasions. AB - We provide an overview of the current state of knowledge of parasites in biological invasions by alien species. Parasites have frequently been invoked as drivers of invasions, but have received less attention as invasion passengers. The evidence to date that parasites drive invasions by hosts is weak: while there is abundant evidence that parasites have effects in the context of alien invasions, there is little evidence to suggest that parasites have differential effects on alien species that succeed versus fail in the invasion process. Particular case studies are suggestive but not yet informative about general effects. What evidence there is for parasites as aliens suggests that the same kind of factors determine their success as for non-parasites. Thus, availability is likely to be an important determinant of the probability of translocation. Establishment and spread are likely to depend on propagule pressure and on the environment being suitable (all necessary hosts and vectors are present); the likelihood of both of these dependencies being favourable will be affected by traits relating to parasite life history and demography. The added complication for the success of parasites as aliens is that often this will depend on the success of their hosts. We discuss how these conclusions help us to understand the likely effects of parasites on the success of establishing host populations (alien or native). PMID- 26822782 TI - A current-driven nanometer water pump. AB - The design of a water pump, which has huge potential for applications in nanotechnology and daily life, is the dream of many scientists. In this paper, we successfully design a nanometer water pump by using molecular dynamics simulations. Ions of either sodium or chlorine in a narrow channel will generate electric current under electric fields, which then drives the water through a wider channel, similar to recent experimental setups. Considerable water flux is achieved within small field strengths that are accessible by experimentation. Of particular interest, is that for sodium the water flux increases almost linearly with field strengths; while for chlorine there exists a critical field strength, the water flux exhibits a plateau before the critical value and increases linearly after it. This result follows the behavior of ion velocity, which is related to friction behavior. We also estimate the power and energy consumption for such a pump, and compare it to the macroscopic mechanical pumps. A further comparison suggests that different ions will have different pumping abilities. This study not only provides new, significant results with possible connection to existing research, but has tremendous potential application in the design of nanofluidic devices. PMID- 26822781 TI - Untangling the Complexity of Liver Fluke Infection and Cholangiocarcinoma in NE Thailand Through Transdisciplinary Learning. AB - This study demonstrates how a transdisciplinary learning approach provided new insights for explaining persistent Opisthorchis viverrini infection in northern Thailand, as well as elucidating problems of focusing solely on the parasite as a means of addressing high prevalence of cholangiocarcinoma. Researchers from diverse backgrounds collaborated to design an investigative homestay program for 72 Singaporean and Thai university students in five northeast Thai villages. The students explored how liver fluke infection and potential cholangiocarcinoma development are influenced by local landscape dynamics, aquatic ecology, livelihoods, food culture and health education. Qualitative fieldwork was guided daily by the researchers in a collaborative, co-learning process that led to viewing this health issue as a complex system, influenced by interlinked multidimensional factors. Our transdisciplinary experience has led us to believe that an incomplete understanding of these linkages may reduce the efficacy of interventions. Further, viewing liver fluke infection and cholangiocarcinoma as the same issue is inadvisable. Although O. viverrini infection is an established risk factor for the development of cholangiocarcinoma, multiple factors are known to influence the likelihood of acquiring either. Understanding the importance of the current livelihood transition, landscape modification and the resulting mismatch between local cultures and new socio-ecological settings on cholangiocarcinoma initiation and liver fluke transmission is of critical importance as it may help readjust our view of the respective role of O. viverrini and other socioeconomic risk factors in cholangiocarcinoma etiology and refine intervention strategies. As demonstrated in this study, transdisciplinary approaches have the potential to yield more nuanced perspectives to complex diseases than research that focuses on specific aspects of their epidemiology. They may therefore be valuable when designing effective solutions to context sensitive diseases such as liver fluke infection and cholangiocarcinoma. PMID- 26822783 TI - Baseline prevalence and intensity of schistosomiasis at sentinel sites in Madagascar: Informing a national control strategy. AB - BACKGROUND: Schistosomiasis affects more than 800 million people, mostly in sub Saharan Africa. A baseline sentinel site study was conducted in the Western half of Madagascar to determine the prevalence and intensity of schistosomiasis and soil-transmitted helminth (STH) infections prior to mass drug administration, and to explore the associations between infection and school attendance, and access to water, sanitation and hygiene (WASH) facilities. METHODS: A three-stage, cluster-randomised cross-sectional study was conducted in 29 sentinel sites in October 2015. Twenty school attending and 4 non-attending children in each of the age groups from 7 to 10 years old were randomly selected at each site for detection of Schistosoma haematobium eggs in a single urine slide by filtration, and of S. mansoni, Ascaris lumbricoides, Trichuris trichiura and hookworm eggs in duplicate Kato-Katz slides from a single stool sample. School attendance was registered individually, and school-level access to WASH facilities was scored through pre-defined observed and reported factors. Logistic regression analysis was performed, adjusting for gender, age and study site. School-level WASH status was analysed using Spearman's rank correlation coefficient. RESULTS: A total of 1,958 children were included. The prevalence of S. haematobium infection and heavy-intensity infection was 30.5% and 15.1%, respectively. The prevalence of S. mansoni infection and heavy-intensity infection was 5.0% and 0.9%, respectively. The prevalence of any STH infection was 4.7%. There was no significant difference in prevalence of infection or heavy-intensity infection of either schistosome species between attending and non-attending children, apart from heavy-intensity S. mansoni infection that was significantly more common in children who did not attend school regularly (aOR = 7.5 (95% CI = 1.1-49.5); p = 0.037). Only a minority of schools had adequate access to WASH facilities, and in this study, we found no significant association between school-level WASH status and schistosomiasis. CONCLUSIONS: This study found an alarmingly high prevalence and intensity of schistosomiasis, and the results warrant urgent scale-up of the national NTD control programme that will need to include both non-attending and attending school-age children in order to reach WHO roadmap targets for the control of schistosomiasis by 2020. PMID- 26822784 TI - CLTC as a clinically novel gene associated with multiple malformations and developmental delay. AB - Diagnostic exome sequencing has recently emerged as an invaluable tool in determining the molecular etiology of cases involving dysmorphism and developmental delay that are otherwise unexplained by more traditional methods of genetic testing. Our patient was large for gestational age at 35 weeks, delivered to a 27-year-old primigravid Caucasian whose pregnancy was complicated by preeclampsia. Neonatal period was notable for hypoglycemia, apnea, bradycardia, hyperbilirubinemia, grade I intraventricular hemorrhage, subdural hematoma, laryngomalacia, hypotonia, and feeding difficulties. The patient had numerous minor dysmorphic features. At three and a half years of age, she has global developmental delays and nystagmus, and is being followed for a mediastinal neuroblastoma that is currently in remission. Karyotype and oligo-microarray were normal. Whole-exome, next generation sequencing (NGS) coupled to bioinformatic filtering and expert medical review at Ambry Genetics revealed 14 mutations in 9 genes, and these genes underwent medical review. A heterozygous de novo frameshift mutation, c.2737_2738dupGA p.D913Efs*59, in which two nucleotides are duplicated in exon 17 of the CLTC gene, results in substitution of glutamic acid for aspartic acid at position 913 of the protein, as well as a frame shift that results in a premature termination codon situated 58 amino acids downstream. Clathrin Heavy Chain 1 (CHC1) has been shown to play an important role in the brain for vesicle recycling and neurotransmitter release at pre-synaptic nerve terminals. There is also evidence implicating it in the proper development of the placenta during the early stages of pregnancy. The CLTC alteration identified herein is likely to provide an explanation for the patient's adverse phenotype. Ongoing functional studies will further define the impact of this alteration on CHC1 function and consequently, human disease. PMID- 26822785 TI - A multi-substrate approach for functional metagenomics-based screening for (hemi)cellulases in two wheat straw-degrading microbial consortia unveils novel thermoalkaliphilic enzymes. AB - BACKGROUND: Functional metagenomics is a promising strategy for the exploration of the biocatalytic potential of microbiomes in order to uncover novel enzymes for industrial processes (e.g. biorefining or bleaching pulp). Most current methodologies used to screen for enzymes involved in plant biomass degradation are based on the use of single substrates. Moreover, highly diverse environments are used as metagenomic sources. However, such methods suffer from low hit rates of positive clones and hence the discovery of novel enzymatic activities from metagenomes has been hampered. RESULTS: Here, we constructed fosmid libraries from two wheat straw-degrading microbial consortia, denoted RWS (bred on untreated wheat straw) and TWS (bred on heat-treated wheat straw). Approximately 22,000 clones from each library were screened for (hemi)cellulose-degrading enzymes using a multi-chromogenic substrate approach. The screens yielded 71 positive clones for both libraries, giving hit rates of 1:440 and 1:1,047 for RWS and TWS, respectively. Seven clones (NT2-2, T5-5, NT18-17, T4-1, 10BT, NT18-21 and T17-2) were selected for sequence analyses. Their inserts revealed the presence of 18 genes encoding enzymes belonging to twelve different glycosyl hydrolase families (GH2, GH3, GH13, GH17, GH20, GH27, GH32, GH39, GH53, GH58, GH65 and GH109). These encompassed several carbohydrate-active gene clusters traceable mainly to Klebsiella related species. Detailed functional analyses showed that clone NT2-2 (containing a beta-galactosidase of ~116 kDa) had highest enzymatic activity at 55 degrees C and pH 9.0. Additionally, clone T5-5 (containing a beta-xylosidase of ~86 kDa) showed > 90% of enzymatic activity at 55 degrees C and pH 10.0. CONCLUSIONS: This study employed a high-throughput method for rapid screening of fosmid metagenomic libraries for (hemi)cellulose degrading enzymes. The approach, consisting of screens on multi-substrates coupled to further analyses, revealed high hit rates, as compared with recent other studies. Two clones, 10BT and T4-1, required the presence of multiple substrates for detectable activity, indicating a new avenue in library activity screening. Finally, clones NT2-2, T5-5 and NT18-17 were found to encode putative novel thermo-alkaline enzymes, which could represent a starting point for further biotechnological applications. PMID- 26822786 TI - Arbitrary thresholds of natural variability and severity should not be used to diagnose chronic obstructive pulmonary disease. PMID- 26822787 TI - Management of hyper-flexion injury-related teardrop fracture in an adolescent. AB - We present a case of a flexion teardrop fracture managed surgically with anterior stabilisation and fusion between the affected vertebral body to its posteriorly adjacent level. A 14-year-old girl presented with severe neck pain following a fall from a bunk bed. MRI investigation showed signs of axial loading and hyper flexion yielding a teardrop fracture at the body of the C5 vertebra. Using a novel technique, the patient was treated surgically with an anterior fusion of the C5-C6 vertebra. Her 12-month follow-up demonstrated full functional ability. PMID- 26822788 TI - Accuracy of clinical criteria and an immunochromatographic strip test for dengue diagnosis in a DENV-4 epidemic. AB - BACKGROUND: Early diagnosis of dengue infection is important for decision-making and timely implementation of therapeutic measures. Although rapid NS1 assays have been used for dengue diagnosis since 2008, their performance in DENV-4 cases has not yet been fully assessed. METHODS: We evaluated the accuracy of NS1 BioeasyTM immunochromatographic strip test and of three clinical criteria for dengue diagnosis. Patients presenting at an emergency care center within 72 h of an acute febrile illness during the 2013 DENV-4 epidemic in Rio de Janeiro were consecutively enrolled for clinical and laboratory evaluation. We classified patients as suspected dengue or not according to three clinical criteria: WHO 2009, WHO 1997, and INI-FIOCRUZ. Dengue diagnosis was defined by RNA detection using RT-PCR and the negative cases were negative for all dengue serotypes and also PlateliaTM NS1 ELISA. We obtained accuracy indices for NS1 BioeasyTM alone and in combination with the clinical criteria. RESULTS: RT-PCR for DENV-4 was positive in 148 out of 325 patients. Positive likelihood ratio, sensitivity, and specificity of NS1 BioeasyTM with WHO 2009, WHO 1997, and INI-FIOCRUZ criteria were 22.6 (95% CI 7.2-70.6), 40.6% (95% CI 32.3-49.3), and 98.2% (95% CI 94.9 99.6); 18.3 (95% CI 6.8-49.2), 44.2 (95% CI 35.8-52.9), 97.6 (95% CI 94.0-99.3); 26.2 (95% CI 6.5-106.5), 29.7 (95% CI 22.4-37.8), 98.9 (95% CI 96.0-99.9), respectively. WHO 1997 clinical criteria presented high sensitivity to rule out disease, but extremely low specificity. INI-FIOCRUZ had moderate sensitivity and specificity, and could target a group to a more specific test. CONCLUSIONS: Although the large rates of false negative results using NS1 BioeasyTM rapid test advise against its use for triaging (rule out) purposes in DENV-4 epidemics, it could be used as a confirmatory tool in a bedside algorithm. PMID- 26822789 TI - Development of a Specific Monoclonal Antibody for the Quantification of Artemisinin in Artemisia annua and Rat Serum. AB - Artemisinin, extracted from Artemisia annua, and its derivatives are important frontline antimalarials. To produce specific antibodies for the detection and quantification of artemisinin, artemisinin was transformed to 9 hydroxyartemisinin by microbial fermentation, which was used to prepare a 9 succinate artemisinin hapten for conjugation with ovalbumin. A monoclonal antibody (mAb), designated as 3H7A10, was selected from hybridoma cell lines which showed high specificity to artemisinin. No competitive inhibition was observed with artesunate, dihydroartemisinin, and artemether for up to 20,000 ng mL(-1). An indirect competitive enzyme-linked immunosorbent assay (icELISA) was developed, which showed a concentration causing 50% of inhibition (IC50) for artemisinin as 2.6 ng mL(-1) and a working range of 0.6-11.5 ng mL(-1). The icELISA was applied for the quantification of artemisinin in crude extracts of wild A. annua and the study of pharmacokinetics of artemisinin in rat serum after intraperitoneal injection. The results were highly correlated with those determined by HPLC-UV analysis (R(2) = 0.9919). In comparison with reported antiartemisinin mAbs which have broad cross-reactivity with other artemisinin derivatives, the high specificity of 3H7A10 for artemisinin will enable development of methods for quantification of artemisinin in Artemisia plants and antimalarial drugs such as Arco and for pharmacokinetic studies. PMID- 26822790 TI - Efficacy and safety of mineralocorticoid receptor antagonists for patients with heart failure and diabetes mellitus: a systematic review and meta-analysis. AB - BACKGROUND: The aim of this study was to systematically assess the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) for patients with heart failure (HF) and diabetes mellitus (DM). METHODS: We conducted a comprehensive search for controlled studies that evaluated the efficacy and safety of MRAs in patients with DM and HF. Medline, Embase and Cochrane databases were searched. Two reviewers independently identified citations, extracted data and evaluated quality. Risk estimations were abstracted and pooled where appropriate. RESULTS: Four observational studies were included. MRAs use was associated with reduced mortality compared with controls (RR = 0.78; 95% CI: 0.69-0.88; I(2) = 0%; P < 0.001). Increased risk of developing hyperkalaemia was observed in those patients taking MRAs (RR = 1.74; 95% CI: 1.27-2.38; I(2) = 0%; P = 0.0005). CONCLUSIONS: The current cumulative evidence suggests that MRAs can improve clinical outcomes but increase the risk of hyperkalaemia in patients with DM and HF. TRIAL REGISTRATION: PROSPERO CRD42015025690 . PMID- 26822791 TI - Dronabinol increases pain threshold in patients with functional chest pain: a pilot double-blind placebo-controlled trial. AB - Noncardiac chest pain is associated with poor quality of life and high care expenditure. The majority of noncardiac chest pain is either gastresophageal reflux disease related or due to esophageal motility disorders, and the rest are considered functional chest pain (FCP) due to central and peripheral hypersensitivity. Current treatment of FCP improves 40-50% of patients. Cannabinoid receptors 1 (CB1) and 2 (CB2) modulate release of neurotransmitters; CB1 is located in the esophageal epithelium and reduces excitatory enteric transmission and potentially could reduce esophageal hypersensitivity. We performed a prospective study to evaluate its effects on pain threshold, frequency, and intensity in FCP. Subjects with FCP received dronabinol (5 mg, twice daily; n = 7; average age, 44 years; mean body mass index, 26.7) or placebo (n = 6; average age, 42 years; mean body mass index, 25.9) for 28 days (4 weeks). Chest pain, general health, and anxiety/depression questionnaires were assessed at baseline and at 4 weeks. Subjects underwent an esophageal balloon distention test prior to treatment and on last day of the study. Dronabinol increased pain thresholds significantly (3.0 vs. 1.0; P = 0.03) and reduced pain intensity and odynophagia compared to placebo (0.18 vs. 0.01 and 0.12 vs. 0.01, respectively, P = 0.04). Depression and anxiety scores did not differ between the groups at baseline or after treatment. No significant adverse effects were observed. In this novel study, dronabinol increased pain threshold and reduced frequency and intensity of pain in FCP. Further, large scale studies are needed to substantiate these findings. PMID- 26822792 TI - Trends in burnout syndrome and emotional factors: an assessment of anesthesiologists in Southern Brazil, 2012. AB - Burnout syndrome (BOS) is the result of chronic stress at work, and is characterized by emotional exhaustion (EE), depersonalization (DP), and low professional accomplishment. Anesthesiologyis a stressful profession. The aim of this study was to assess the prevalence of burnout as well as the sociodemographic and working characteristics associated with this syndrome's emotional factors, in anesthesiologists from Southern Brazil. We assessed burnout severity, depressive symptoms, and self-esteem using the Maslach burnout inventory, the Beck depression inventory, and the Rosenberg self-esteem scale, respectively. Of the 198 anesthesiologists included in this study, 48.7% were positive for burnout, 26.9% for EE, 41.3% for DP and 32.7% for low personal accomplishment. Trends in BOS was associated with a younger age, difficulty to conciliate family and work demands, low self-esteem, and depressive symptoms. PMID- 26822793 TI - Progress toward meeting the needs of adolescent females with bleeding disorders. PMID- 26822794 TI - High dose CD11c-driven IL15 is sufficient to drive NK cell maturation and anti tumor activity in a trans-presentation independent manner. AB - The common gamma (gammac)-chain cytokine interleukin 15 (IL15) is a multifunctional immune-modulator which impacts the generation, maturation and activity of many cell types of the innate, as well as the adaptive immune system, including natural killer (NK) and CD8(+) T cells. Using a new series of transgenic mice, we analyzed the in vivo potential of IL15 as an immune-regulator when available at different concentrations or delivery modes, i.e. soluble monomer or complexed to its specific receptor alpha (Ralpha)-chain. We have identified distinct effects on selected IL15-responsive populations. While CD8(+) T cells required complexed forms of IL15/IL15Ralpha for full functionality, mature NK populations were rescued in an IL15/IL15Ralpha-deficient environment by high levels of CD11c-restricted IL15. These IL15-conditions were sufficient to limit tumor formation in a lung metastasis model indicating that the NK cell populations were fully functional. These data underline the potential of "free" IL15 in the absence of Ralpha-complex as a powerful and specific immuno modulator, which may be beneficial where selective immune-activation is desired. PMID- 26822795 TI - Evaluation of the Impact of the Revised National Institute for Occupational Safety and Health Lifting Equation. AB - OBJECTIVE: The objective of this article is to evaluate the impact of the Revised National Institute for Occupational Safety and Health Lifting Equation (RNLE). BACKGROUND: The RNLE has been used extensively as a risk assessment method for prevention of low back pain (LBP). However, the impact of the RNLE has not been documented. METHODS: A systematic review of the literature on the RNLE was conducted. The review consisted of three parts: characterization of the RNLE publications, assessment of the impact of the RNLE, and evaluation of the influences of the RNLE on ergonomic standards. The literature for assessing the impact was categorized into four research areas: methodology, laboratory, field, and risk assessment studies using the Lifting Index (LI) or Composite LI (CLI), both of which are the products of the RNLE. RESULTS: The impact of the RNLE has been both widespread and influential. We found 24 studies that examined the criteria used to define lifting capacity used by the RNLE, 28 studies that compared risk assessment methods for identifying LBP, 23 studies that found the RNLE useful in identifying the risk of LBP with different work populations, and 13 studies on the relationship between LI/CLI and LBP outcomes. We also found evidence on the adoption of the RNLE as an ergonomic standard for use by various local, state, and international entities. CONCLUSION: The review found 13 studies that link LI/CLI to adverse LBP outcomes. These studies showed a positive relationship between LI/CLI metrics and the severity of LBP outcomes. PMID- 26822797 TI - Having hands and moral status: a reply to Curtis and Vehmas. AB - Curtis and Vehmas apply the form of Moore's 'Proof of an External World' to justify continuing to believe that all and only humans have full moral status in the absence of a plausible account of why. I note that the strategy is better suited for the sceptical problems Moore applies it to and suggest that resorting to it reflects too great a pessimism about the accounts available. PMID- 26822796 TI - Effects of Information Availability on Command-and-Control Decision Making: Performance, Trust, and Situation Awareness. AB - OBJECTIVE: We investigated how increases in task-relevant information affect human decision-making performance, situation awareness (SA), and trust in a simulated command-and-control (C2) environment. BACKGROUND: Increased information is often associated with an improvement of SA and decision-making performance in networked organizations. However, previous research suggests that increasing information without considering the task relevance and the presentation can impair performance. METHOD: We used a simulated C2 task across two experiments. Experiment 1 varied the information volume provided to individual participants and measured the speed and accuracy of decision making for task performance. Experiment 2 varied information volume and information reliability provided to two participants acting in different roles and assessed decision-making performance, SA, and trust between the paired participants. RESULTS: In both experiments, increased task-relevant information volume did not improve task performance. In Experiment 2, increased task-relevant information volume reduced self-reported SA and trust, and incorrect source reliability information led to poorer task performance and SA. CONCLUSION: These results indicate that increasing the volume of information, even when it is accurate and task relevant, is not necessarily beneficial to decision-making performance. Moreover, it may even be detrimental to SA and trust among team members. APPLICATION: Given the high volume of available and shared information and the safety-critical and time sensitive nature of many decisions, these results have implications for training and system design in C2 domains. To avoid decrements to SA, interpersonal trust, and decision-making performance, information presentation within C2 systems must reflect human cognitive processing limits and capabilities. PMID- 26822798 TI - The clinician and detention. PMID- 26822800 TI - Prepartum and Postpartum Maternal Depressive Symptoms Are Related to Children's Brain Structure in Preschool. AB - BACKGROUND: Perinatal maternal depression is a serious health concern with potential lasting negative consequences for children. Prenatal depression is associated with altered brain gray matter in children, though relations between postpartum depression and children's brains and the role of white matter are unclear. METHODS: We studied 52 women who provided Edinburgh Postnatal Depression Scale (EPDS) scores during each trimester of pregnancy and at 3 months postpartum and their children who underwent magnetic resonance imaging at age 2.6 to 5.1 years. Associations between maternal depressive symptoms and magnetic resonance imaging measures of cortical thickness and white matter structure in the children were investigated. RESULTS: Women's second trimester EPDS scores negatively correlated with children's cortical thickness in right inferior frontal and middle temporal regions and with radial and mean diffusivity in white matter emanating from the inferior frontal area. Cortical thickness, but not diffusivity, correlations survived correction for postpartum EPDS. Postpartum EPDS scores negatively correlated with children's right superior frontal cortical thickness and with diffusivity in white matter originating from that region, even after correcting for prenatal EPDS. CONCLUSIONS: Higher maternal depressive symptoms prenatally and postpartum are associated with altered gray matter structure in children; the observed white matter correlations appear to be uniquely related to the postpartum period. The reduced thickness and diffusivity suggest premature brain development in children exposed to higher maternal perinatal depressive symptoms. These results highlight the importance of ensuring optimal women's mental health throughout the perinatal period, because maternal depressive symptoms appear to increase children's vulnerability to nonoptimal brain development. PMID- 26822801 TI - Mutations in the beta-globin gene from a Saudi population: an update. PMID- 26822799 TI - Effects of Creatine Monohydrate Augmentation on Brain Metabolic and Network Outcome Measures in Women With Major Depressive Disorder. AB - BACKGROUND: Creatine monohydrate (creatine) augmentation has the potential to accelerate the clinical responses to and enhance the overall efficacy of selective serotonin reuptake inhibitor treatment in women with major depressive disorder (MDD). Although it has been suggested that creatine augmentation may involve the restoration of brain energy metabolism, the mechanisms underlying its antidepressant efficacy are unknown. METHODS: In a randomized, double-blind, placebo-controlled trial, 52 women with MDD were assigned to receive either creatine augmentation or placebo augmentation of escitalopram; 34 subjects participated in multimodal neuroimaging assessments at baseline and week 8. Age matched healthy women (n = 39) were also assessed twice at the same intervals. Metabolic and network outcomes were measured for changes in prefrontal N acetylaspartate and changes in rich club hub connections of the structural brain network using proton magnetic resonance spectroscopy and diffusion tensor imaging, respectively. RESULTS: We found MDD-related metabolic and network dysfunction at baseline. Improvement in depressive symptoms was greater in patients receiving creatine augmentation relative to placebo augmentation. After 8 weeks of treatment, prefrontal N-acetylaspartate levels increased significantly in the creatine augmentation group compared with the placebo augmentation group. Increment in rich club hub connections was also greater in the creatine augmentation group than in the placebo augmentation group. CONCLUSIONS: N acetylaspartate levels and rich club connections increased after creatine augmentation of selective serotonin reuptake inhibitor treatment. Effects of creatine administration on brain energy metabolism and network organization may partly underlie its efficacy in treating women with MDD. PMID- 26822802 TI - Focus on five patients treated with cyclosporine up to 62 months. AB - BACKGROUND: Cyclosporine is a validated treatment for moderate to severe psoriasis. Long-term cyclosporine administration may induce toxic effects. The duration of treatment usually ranges from 10 to 16 weeks. However, some patients may take cyclosporine for a longer time. AIM: The objective of the present study is to evaluate the dose, efficacy and safety in long-term cyclosporine therapy. PATIENTS AND METHODS: We studied the hospital records of patients with psoriasis treated with cyclosporine between 1 January 2009, and 30 April 2015. We decided to focus on patients who, for different reasons, have continued cyclosporine for more than 2 years. RESULTS: Five patients (2.69%) had been assuming cyclosporine for up to 62 months and had achieved a substantial response with no toxic effects. All of them were concerned about recurrence and all patients had personal reasons to prefer Cyclosporine over other drugs, including: familiar history of neurodegenerative disease, desire for motherhood, easy availability on prescription, systemic scleroderma, belenophobia. CONCLUSION: Cyclosporine is an acceptable monotherapy for psoriasis in selected patients. The prompt discontinuation of treatment usually results in resolution of any eventual toxicity. PMID- 26822803 TI - Optimum combination therapy regimens for HIV/HCV infection. AB - HIV-HCV co-infection mostly affects intravenous drug users, in whom prevalence has tended to decrease in recent years, while it has increased in men who have sex with men, with occurrence of acute hepatitis C. Hepatitis C has a poorer prognosis in patients co-infected with HIV, as clinical progression is faster and degree of hepatic fibrosis is greater. However, optimized ARV treatment is clearly associated with slower progression to hepatic complications. Interactions between HCV and HIV drugs are numerous, which underlines the importance of pharmacological advice for HIV-treated patients before they start HCV treatment. In HIV-HCV co-infection, treatment of hepatitis C has to be offered as in mono infected patients (US and European countries) or to all patients (French guidelines). In most patients, HCV eradication is achieved with different DAA associations, the choice and duration being driven by HCV genotype, hepatic fibrosis stage, and whether patients have been previously treated or not. PMID- 26822804 TI - Measurement of heart rate variability using off-the-shelf smart phones. AB - BACKGROUND: The cardiac parameters, such as heart rate (HR) and heart rate variability (HRV), are very important physiological data for daily healthcare. Recently, the camera-based photoplethysmography techniques have been proposed for HR measurement. These techniques allow us to estimate the HR contactlessly with low-cost camera. However, the previous works showed limit success for estimating HRV because the R-R intervals, the primary data for HRV calculation, are sensitive to noise and artifacts. METHODS: This paper proposed a non-contact method to extract the blood volume pulse signal using a chrominance-based method followed by a proposed CWT-based denoising technique. The R-R intervals can then be obtained by finding the peaks in the denoised signal. In this paper, we taped 12 video clips using the frontal camera of a smart phone with different scenarios to make comparisons among our method and the other alternatives using the absolute errors between the estimated HRV metrics and the ones obtained by an ECG accurate chest band. RESULTS: As shown in experiments, our algorithm can greatly reduce absolute errors of HRV metrics comparing with the related works using RGB color signals. The mean of absolute errors of HRV metrics from our method is only 3.53 ms for the static-subject video clips. CONCLUSIONS: The proposed camera based method is able to produce reliable HRV metrics which are close to the ones measured by contact devices under different conditions. Thus, our method can be used for remote health monitoring in a convenient and comfortable way. PMID- 26822805 TI - Considering risk contexts in explaining the paradoxical HIV increase among female sex workers in Mumbai and Thane, India. AB - BACKGROUND: The period 2006-2009 saw intensive scale-up of HIV prevention efforts and an increase in reported safer sex among brothel and street-based sex workers in Mumbai and Thane (Maharashtra, India). Yet during the same period, the prevalence of HIV increased in these groups. A better understanding of sex workers' risk environment is needed to explain this paradox. METHODS: In this qualitative study we conducted 36 individual interviews, 9 joint interviews, and 10 focus group discussions with people associated with HIV interventions between March and May 2012. RESULTS: Dramatic changes in Mumbai's urban landscape dominated participants' accounts, with dwindling sex worker numbers in traditional brothel areas attributed to urban restructuring. Gentrification and anti-trafficking efforts explained an escalation in police raids. This contributed to dispersal of sex work with the sex-trade management adapting by becoming more hidden and mobile, leading to increased vulnerability. Affordable mobile phone technology enabled independent sex workers to trade in more hidden ways and there was an increased dependence on lovers for support. The risk context has become ever more challenging, with animosity against sex work amplified since the scale up of targeted interventions. Focus on condom use with sex workers inadvertently contributed to the diversification of the sex trade as clients seek out women who are less visible. Sex workers and other marginalised women who sell sex all strictly prioritise anonymity. Power structures in the sex trade continue to pose insurmountable barriers to reaching young and new sex workers. Economic vulnerability shaped women's decisions to compromise on condom use. Surveys monitoring HIV prevalence among 'visible' street and brothel-bases sex workers are increasingly un-representative of all women selling sex and self reported condom use is no longer a valid measure of risk reduction. CONCLUSIONS: Targeted harm reduction programmes with sex workers fail when implemented in complex urban environments that favour abolition. Increased stigmatisation and dispersal of risk can no longer be considered as unexpected. Reaching the increasing proportion of sex workers who intentionally avoid HIV prevention programmes has become the main challenge. Future evaluations need to incorporate building 'dark logic' models to predict potential harms. PMID- 26822806 TI - Erratum: Investigation of the fatty acid transporter-encoding genes SLC27A3 and SLC27A4 in autism. PMID- 26822807 TI - Development of Singlet Oxygen Absorption Capacity (SOAC) Assay Method Using a Microplate Reader. AB - Recently, a new assay method that can quantify the singlet oxygen absorption capacity (SOAC) of natural antioxidants and food extracts was developed. The SOAC values were measured in ethanol-chloroform-D2O (50 + 50 + 1, v/v/v) solution at 35 degrees C using a UV-Vis spectrophotometer equipped with a six-channel cell positioner and an electron-temperature control unit. In the present study, measurement of the SOAC values was performed for eight representative carotenoids and three vegetable extracts (tomato, carrot, and red paprika) using a versatile instrument, the microplate reader. A 24-well glass microplate was used for measurements because a plastic microplate, commonly used in the laboratory, dissolves in the ethanol-chloroform-D2O solution. The SOAC values of eight carotenoids and three vegetable extracts measured using a microplate reader were in good agreement with the corresponding values measured using a UV-Vis spectrophotometer, suggesting that the microplate reader is an applicable instrument for the measurement of reliable SOAC values for general antioxidants and food extracts in solution. PMID- 26822808 TI - Prevalence of probiotic use among inpatients: A descriptive study of 145 U.S. hospitals. AB - BACKGROUND: To inform clinical guidance, public health efforts, and research directions, probiotic use in U.S. health care needs to be better understood. This work aimed to assess the prevalence of inpatient probiotic use in a sample of U.S. hospitals. METHODS: Probiotic use among patients discharged in 2012 was estimated using the MarketScan Hospital Drug Database. In addition, the annual trend in probiotic use (2006-2012) was assessed among a subset of hospitals. RESULTS: Among 145 hospitals with 1,976,167 discharges in 2012, probiotics were used in 51,723 (2.6%) of hospitalizations occurring in 139 (96%) hospitals. Patients receiving probiotics were 9 times more likely to receive antimicrobials (P < .0001) and 21 times more likely to have a Clostridium difficile infection diagnosis (P < .0001). The most common probiotic formulations were Saccharomyces boulardii (32% of patients receiving probiotics), Lactobacillus acidophilus and Lactobacillus bulgaricus (30%), L acidophilus (28%), and Lactobacillus rhamnosus (11%). Probiotic use increased from 1.0% of 1,090,373 discharges in 2006 to 2.9% of 1,006,051 discharges in 2012 (P < .0001). CONCLUSIONS: In this sample of U.S. hospitals, a sizable and growing number of inpatients received probiotics as part of their care despite inadequate evidence to support their use in this population. Additional research is needed to guide probiotic use in the hospital setting. PMID- 26822810 TI - The Echocardiographic "Spike and Dome"--Obstruction It Is But Where? AB - Spectral Doppler interrogation of the descending thoracic and abdominal aorta provides valuable information regarding cardiac and vascular hemodynamics. An abnormal aortic Doppler profile is encountered in pathological conditions that affect the aorta and its branches, the aortic valve, the left ventricle, and the pericardium. Characteristic findings on Doppler interrogation of the aorta are often noted in individuals with obstructive atherosclerotic disease of the aorto iliac system including severe stenosis or occlusion of the distal aorta and/or iliac arteries. In this manuscript, we highlight the findings on spectral Doppler that led to the identification of occlusive disease in the distal aorta. PMID- 26822809 TI - A novel role for the deubiquitinase USP1 in the control of centrosome duplication. AB - Defects in the regulation of centrosome duplication lead to tumorigenesis through abnormal cell division and resulting chromosome missegregation. Therefore, maintenance of accurate centrosome number is critical for cell fate. The deubiquitinating enzyme USP1 plays important roles in DNA repair and cell differentiation. Importantly, increased levels of USP1 are detected in certain types of human cancer, but little is known about the significance of USP1 overexpression in cancer development. Here we show that Usp1 plays a novel role in regulating centrosome duplication. The ectopic expression of wild-type Usp1, but not C90S Usp1 (catalytically inactive mutant form), induced centrosome amplification. Conversely, ablation of Usp1 in mouse embryonic fibroblasts (MEFs) showed a significant delay in centrosome duplication. Moreover, Usp1-induced centrosome amplification caused abnormal mitotic spindles, chromosome missegregation and aneuploidy. Interestingly, loss of inhibitor of DNA binding protein 1 (ID1) suppressed Usp1-induced centrosome amplification. Taken together, our results strongly suggest that Usp1 is involved in the regulation of centrosome duplication, at least in part via ID1, and Usp1 may exert its oncogenic activity, partially through inducing centrosome abnormality. PMID- 26822811 TI - Nutritional supplementation in patients with chronic obstructive pulmonary disease. AB - Malnutrition in patients with chronic obstructive pulmonary disease (COPD) is associated with cachexia, sarcopenia, and weight loss, and may result in poorer pulmonary function, decreased exercise capacity, and increased risk of exacerbations. Providing nutritional supplementation is an important therapeutic intervention, particularly for severely ill COPD patients with malnutrition. Higher calorie intake through nutritional supplementation significantly increases body weight and muscle strength, and improves quality of life in malnourished COPD patients. Difficulties may be experienced by these COPD patients, who are struggling to breathe and eliminate CO2 from the lungs, resulting in dyspnea, hypercapnia, hypoxia, and respiratory acidosis, which exacerbates muscle loss through oxidative stress and inflammatory responses. To overcome these problems, nutritional supplements should aim to reduce metabolic CO2 production, lower respiratory quotient, and improve lung function. Several studies have shown that high-fat supplements produce less CO2 and have lower respiratory quotient value than high-carbohydrate supplements. In addition, high-fat supplements may be the most efficient means of providing a low-volume, calorie-dense supplement to COPD patients, and may be most beneficial to patients with prolonged mechanical ventilation where hypercapnia and malnutrition are most pronounced. Further studies are required to investigate the optimal nutritional supplements for COPD patients according to their disease severity. PMID- 26822812 TI - Solution Layer Deposition: A Technique for the Growth of Ultra-Pure Manganese Oxides on Silica at Room Temperature. AB - With the ever increasing miniaturization in microelectronic devices, new deposition techniques are required to form high-purity metal oxide layers. Herein, we report a liquid route to specifically produce thin and conformal amorphous manganese oxide layers on silicon substrate, which can be transformed into a manganese silicate layer. The undesired insertion of carbon into the functional layers is avoided through a solution metal-organic chemistry approach named Solution Layer Deposition (SLD). The growth of a pure manganese oxide film by SLD takes place through the decoordination of ligands from a metal-organic complex in mild conditions, and coordination of the resulting metal atoms on a silica surface. The mechanism of this chemical liquid route has been elucidated by solid-state (29) Si MAS NMR, XPS, SIMS, and HRTEM. PMID- 26822813 TI - Validity of Teacher-Based Vision Screening and Factors Associated with the Accuracy of Vision Screening in Vietnamese Children. AB - PURPOSE: To assess validity of teacher-based vision screening and elicit factors associated with accuracy of vision screening in Vietnam. METHODS: After brief training, teachers independently measured visual acuity (VA) in 555 children aged 12-15 years in Ba Ria - Vung Tau Province. Teacher VA measurements were compared to those of refractionists. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for uncorrected VA (UVA) and presenting VA (PVA) 20/40 or worse in either eye. Chi-square, Fisher's exact test and multivariate logistic regression were used to assess factors associated with accuracy of vision screening. Level of significance was set at 5%. RESULTS: Trained teachers in Vietnam demonstrated 86.7% sensitivity, 95.7% specificity, 86.7% positive predictive value and 95.7% negative predictive value in identifying children with visual impairment using the UVA measurement. PVA measurement revealed low accuracy for teachers, which was significantly associated with child's age, sex, spectacle wear and myopic status, but UVA measurement showed no such associations. CONCLUSIONS: Better accuracy was achieved in measurement of VA and identification of children with visual impairment using UVA measurement compared to PVA. UVA measurement is recommended for teacher-based vision screening programs. PMID- 26822814 TI - [Prevention of ventilator-associated pneumonia: a comparison of level of knowledge in three critical care units]. AB - OBJECTIVE: To determine the level of knowledge of the prevention of ventilator associated pneumonia guidelines of nurses working in three intensive care units (ICU) in 3 university hospitals in a Spanish region, and evaluate the relationship between this level of knowledge and years worked in the ICU. METHOD: A descriptive, prospective, cross-sectional, multicentre study was conducted using a validated and reliable questionnaire, made up by 9 questions with closed answers drawn from the EVIDENCE study. A total of 98 questionnaires were collected from ICU nurses of the three university hospitals (A, B, and C) from January to April 2014. The sample from hospital A responded the most, in contrast with the sample from hospital B, which was the one with the less participation. The Pearson correlation was calculated in order to determine the relationship between nurse years worked in ICU and level of knowledge. RESULTS: Hospital A obtained in the best mean score in the questionnaire, 6.33 (SD 1.4) points, followed by hospital C with 6.21 (SD 1.4), and finally, the hospital B with 6.06 (SD 1.5) points. A p=.08 was obtained on relating years worked with the level of knowledge. CONCLUSION: The results showed a high level of knowledge compared other studies. There was a tendency between the years worked in the unit and the level of knowledge in ventilator-associated pneumonia prevention. PMID- 26822815 TI - The role of anesthesia in the prevention of postoperative delirium: a systematic review. AB - INTRODUCTION: Postoperative delirium (POD) is defined as an acute neurologic insult characterized by changes in consciousness and cognition, altered perception and a fluctuating course. It leads to poor outcome and increased health care system costs. Considering its high incidence, up to 60%, and the lack of a first-choice treatment, prevention has become a priority. Our aim was to systematically review literature on POD prevention and to identify the role of anesthesia in this context. EVIDENCE ACQUISITION: MEDLINE and EMBASE were searched for studies considering any anesthetic intervention intended to prevent POD. Risk of bias was assessed with the Quality Assessment Tool for Quantitative Studies for original articles and with the R-AMSTAR checklist for systematic reviews. EVIDENCE SYNTHESIS: A total of 27 studies were included. Interventions included pre-, intra-/peri- and postoperative strategies to prevent POD. Only 9 out of 27 studies had high methodological quality. Use of a depth of anesthesia monitor and lighter sedation had the strongest evidence in reduction of POD. Perioperative dexmedetomidine, ketamine, dexamethasone, and antipsychotic administration may reduce the risk of POD. CONCLUSIONS: Methodologically robust studies supporting strategies for preventing POD are still lacking. Based on our analysis, anesthesiologists should consider the intraoperative use of a depth of anesthesia monitor and the choice for a lighter sedation when possible. The administration of preventive medications should be considered very carefully. Considering the multifactorial nature of POD, however, the integration of effective preventive strategies into multidisciplinary programs is advisable and should be the target for future research. PMID- 26822816 TI - Insurance claims of alleged anesthesiology malpractice in a Spanish series. PMID- 26822817 TI - Tetanus and Tako-Tsubo: is there a relationship? PMID- 26822818 TI - Intravenous immunoglobins in sepsis: the potential risk of overinterpreting a well-done meta-analysis. PMID- 26822819 TI - How should ethical committees promote research in critically ill patients? PMID- 26822820 TI - A year in review in Minerva Anestesiologica 2015. PMID- 26822821 TI - The Validity of a Brief Risk Assessment Tool for Predicting Suicidal Behavior in Veterans Utilizing VHA Mental Health Care. AB - Suicide risk among military veterans is an important and ongoing concern. The Veterans Administration (VA) mandates suicide risk screening of all veterans seen for mental health issues, but little is known about the effectiveness of this screening. A retrospective chart review to examine all suicide risk screens at VA San Diego between October and December 2012 (n = 3,365) was conducted to assess whether results were associated with suicidal behavior over the subsequent 12 months. Patients judged to be at increased risk for suicide were 3 to 16 times more likely to attempt suicide and 7 to 25 times more likely to engage in self directed violence over the next 12 months compared with others. The screening tool may be a useful addition to clinical practice. PMID- 26822822 TI - The safety of influenza vaccines in children: An Institute for Vaccine Safety white paper. AB - Most influenza vaccines are generally safe, but influenza vaccines can cause rare serious adverse events. Some adverse events, such as fever and febrile seizures, are more common in children than adults. There can be differences in the safety of vaccines in different populations due to underlying differences in genetic predisposition to the adverse event. Live attenuated vaccines have not been studied adequately in children under 2 years of age to determine the risks of adverse events; more studies are needed to address this and several other priority safety issues with all influenza vaccines in children. All vaccines intended for use in children require safety testing in the target age group, especially in young children. Safety of one influenza vaccine in children should not be extrapolated to assumed safety of all influenza vaccines in children. The low rates of adverse events from influenza vaccines should not be a deterrent to the use of influenza vaccines because of the overwhelming evidence of the burden of disease due to influenza in children. PMID- 26822823 TI - From the Editor. PMID- 26822824 TI - Incidence of and Factors Associated With Hypogeusia in Healthy Children. AB - IMPORTANCE: There are currently no measures of isolated glossopharyngeal taste in healthy children, to our knowledge. OBJECTIVE: To define the taste characteristics of an otherwise healthy pediatric population that could serve as a control group for further investigations. DESIGN, SETTING, AND PARTICIPANTS: A prospective study of taste and smell was conducted from August 4 to 29, 2014, at a general pediatrics clinic in a tertiary care medical center in 80 healthy children aged 6 to 17 years who were receiving well-child examinations or vaccinations or in their healthy siblings. EXPOSURES: Testing of smell and taste. MAIN OUTCOMES AND MEASURES: Demographic data were gathered on age, sex, and body mass index as well as type of insurance. Smell testing was performed with the National Institutes of Health Toolbox Odor Identification Test, with scores based on national averages for age and sex. Validated Taste Strips were used for testing sweet, salty, sour, and bitter tastes. One strip at a time was placed on the midline of the tongue at the circumvallate papillae in random tastant order and in increasing concentrations. Correct identification of the tastant earned 1 point; of 16 possible points, a score of less than 9 signified hypogeusia. Fisher exact test was used for statistical analysis. RESULTS: The mean (SD) age of the 80 children in this study was 11.3 (3.2) years, and 43 were boys (54%). Hypogeusia was identified in 32 (40%) of the 80 children. Overweight or obesity was identified in 23 children (29%) (15 [31%] with a normal sense of taste and 8 [25%] with hypogeusia; P = .62), and 12 (15%) used public insurance (7 [15%] with a normal sense of taste and 5 [16%] with hypogeusia; P > .99). Age younger than 12 years (24 [50%] with a normal sense of taste and 19 [59%] with hypogeusia; P = .50), male sex (25 [52%] with a normal sense of taste and 18 [56%] with hypogeusia; P = .39), overweight or obesity (15 [31%] with a normal sense of taste and 8 [25%] with hypogeusia; P = .62), insurance type (P > .99), and olfaction less than the 50th percentile (29 [60%] with a normal sense of taste and 17 [53%] with hypogeusia; P = .65) or hyposmia (<10th percentile; P = .47) were not statistically significantly correlated with overall hypogeusia. CONCLUSIONS AND RELEVANCE: A significant proportion of otherwise healthy children have hypogeusia according to previously published criteria. This study will provide baseline data from which future investigations studying taste disturbances in patients with chronic tonsillitis and after tonsillectomy can be compared. PMID- 26822825 TI - Gastric vascular ectasia in children: Case reports. PMID- 26822826 TI - Hypertension and Other Determinants of White Matter Lesions in Stroke Patients. AB - Hypertension is the main risk factor for both white matter lesions (WMLs) and stroke, but many stroke patients do not have WMLs. To find specific determinants of WMLs, the authors assessed 321 ischemic and hemorrhagic stroke patients who had undergone echocardiography. The patients with WMLs (n=160) were more often hypertensive and had a higher systolic blood pressure than the patients without WMLs. However, in a multivariate analysis, only the following variables remained associated with WMLs: (1) age: odds ratio [OR], 1.08 per year (95% confidence interval [CI], 1.06-1.11); (2) left ventricular relative wall thickness (RWT) >=0.52: OR, 2.78 (95% CI, 1.59-4.88); (3) lacunar strokes: OR, 4.15 (95% CI, 1.83 9.44); (4) hemorrhagic strokes: OR, 5.36 (95% CI, 1.57-18.39); and (5) female: OR, 1.91 (95% CI, 1.12-3.27). Thus, the main modifiable risk factor for WMLs was RWT, which proved to be an even stronger risk factor than hypertension. This suggests that RWT might be a useful target in the treatment of hypertension to counteract the appearance of WMLs. PMID- 26822827 TI - Understanding the thermosensitivity of POEGA-based star polymers: LCST-type transition in water vs. UCST-type transition in ethanol. AB - The lower critical solution temperature (LCST) transition in water and the upper critical solution temperature (UCST) transition in ethanol of poly(oligo(ethylene glycol) acrylate) (POEGA)-based core cross-linked star (CCS) polymers have been investigated and compared by employing turbidity, dynamic light scattering (DLS), (1)H NMR and FTIR measurements. Macroscopic phase transitions in water and in ethanol were observed to occur when passing through the transition temperature, as revealed by DLS and turbidity measurements. Analysis by IR indicated that the interactions between the polymer chains and solvent molecules in water are stronger than those in ethanol such that the CCS polymer arm chains in water adopt more extended conformations. Moreover, hydrophobic interaction among the aliphatic groups plays a predominant role in the LCST-type transition in water whereas weak solvation of the polymer chains results in the UCST-type transition in ethanol. Additionally, the LCST-type transition in water was observed to be much more abrupt and complete than the UCST-type transition in ethanol, as suggested by (1)H NMR and IR at the molecular level. Finally, an abnormal "forced hydration" phenomenon was observed during the LCST transition upon heating. This study provides a detailed understanding of the subtle distinctions between the thermal transitions of CCS polymers in two commonly used solvents, which may be useful to guide future materials design for a wide range of applications. PMID- 26822828 TI - Acetylome analysis reveals the involvement of lysine acetylation in biosynthesis of antibiotics in Bacillus amyloliquefaciens. AB - Lysine acetylation is a major post-translational modification that plays an important regulatory role in almost every aspects in both eukaryotes and prokaryotes. Bacillus amyloliquefaciens, a Gram-positive bacterium, is very effective for the control of plant pathogens. However, very little is known about the function of lysine acetylation in this organism. Here, we conducted the first lysine acetylome in B. amyloliquefaciens through a combination of highly sensitive immune-affinity purification and high-resolution LC-MS/MS. Overall, we identified 3268 lysine acetylation sites in 1254 proteins, which account for 32.9% of the total proteins in this bacterium. Till date, this is the highest ratio of acetylated proteins that have been identified in bacteria. Acetylated proteins are associated with a variety of biological processes and a large fraction of these proteins are involved in metabolism. Interestingly, for the first time, we found that about 71.1% (27/38) and 78.6% (22/28) of all the proteins tightly related to the synthesis of three types of pepketides and five families of lipopeptides were acetylated, respectively. These findings suggest that lysine acetylation plays a critical role in the regulation of antibiotics biosynthesis. These data serves as an important resource for further elucidation of the physiological role of lysine acetylation in B. amyloliquefaciens. PMID- 26822830 TI - Huntington disease: Boosting PPARdelta blocks neurodegeneration. PMID- 26822832 TI - Screening: A platform for probing protein-aggregation inhibitors. PMID- 26822829 TI - Epithelial-mesenchymal transition: a new target in anticancer drug discovery. AB - The conversion of cells with an epithelial phenotype into cells with a mesenchymal phenotype, referred to as epithelial-mesenchymal transition, is a critical process for embryonic development that also occurs in adult life, particularly during tumour progression. Tumour cells undergoing epithelial mesenchymal transition acquire the capacity to disarm the body's antitumour defences, resist apoptosis and anticancer drugs, disseminate throughout the organism, and act as a reservoir that replenishes and expands the tumour cell population. Epithelial-mesenchymal transition is therefore becoming a target of prime interest for anticancer therapy. Here, we discuss the screening and classification of compounds that affect epithelial-mesenchymal transition, highlight some compounds of particular interest, and address issues related to their clinical application. PMID- 26822831 TI - G protein-coupled receptors as targets for anti-diabetic therapeutics. AB - The prevalence of obesity and type 2 diabetes (T2D) is increasing worldwide, and these two metabolic disorders are closely linked. Lifestyle modification, including weight loss and exercise, are effective treatments for T2D, but, unfortunately, most patients are unsuccessful at maintaining durable weight reduction and recidivism is all too common. Therefore, safe and efficacious drugs are required for the successful treatment of T2D in a large proportion of patients. Targeting G protein-coupled receptors (GPCRs) in metabolic tissues - such as adipose tissue, liver, muscle, pancreatic islets, immune cells and the central nervous system - has emerged as a key target for current and future anti diabetic compounds. This Opinion focuses on the potential of GPCRs as targets for the discovery of new drugs to successfully treat T2D. PMID- 26822834 TI - Drug delivery: New targets for drug delivery across the BBB. PMID- 26822833 TI - Integrin-based therapeutics: biological basis, clinical use and new drugs. AB - Integrins are activatable molecules that are involved in adhesion and signalling. Of the 24 known human integrins, 3 are currently targeted therapeutically by monoclonal antibodies, peptides or small molecules: drugs targeting the platelet alphaIIbbeta3 integrin are used to prevent thrombotic complications after percutaneous coronary interventions, and compounds targeting the lymphocyte alpha4beta1 and alpha4beta7 integrins have indications in multiple sclerosis and inflammatory bowel disease. New antibodies and small molecules targeting beta7 integrins (alpha4beta7 and alphaEbeta7 integrins) and their ligands are in clinical development for the treatment of inflammatory bowel diseases. Integrin based therapeutics have shown clinically significant benefits in many patients, leading to continued medical interest in the further development of novel integrin inhibitors. Of note, almost all integrin antagonists in use or in late stage clinical trials target either the ligand-binding site or the ligand itself. PMID- 26822835 TI - Lecithin-Based Nano-emulsification Improves the Bioavailability of Conjugated Linoleic Acid. AB - In this study, we investigated the effects of lecithin-based nano-emulsification on the heat stability and bioavailability of conjugated linoleic acid (CLA) in different free fatty acid (FFA) and triglyceride (TG) forms. CLA nano-emulsion in TG form exhibited a small droplet size (70-120 nm) compared to CLA nano-emulsion in FFA form (230-260 nm). Nano-emulsification protected CLA isomers in TG form, but not in free form, against thermal decomposition during the heat treatment. The in vitro bioavailability test using monolayers of Caco-2 human intestinal cells showed that nano-emulsification increased the cellular uptake of CLA in both FFA and TG forms. More importantly, a rat feeding study showed that CLA content in small intestinal tissues or plasma was higher when CLA was emulsified, indicating an enhanced oral bioavailability of CLA by nano-emulsification. These results provide important information for development of nano-emulsion-based delivery systems that improve thermal stability and bioavailability of CLA. PMID- 26822836 TI - Transition metal-free intramolecular regioselective couplings of aliphatic and aromatic C-H bonds. AB - Cross-dehydrogenative couplings of two different C-H bonds have emerged as an attractive goal in organic synthesis. However, achieving regioselective C-H activation is a great challenge because C-H bonds are ubiquitous in organic compounds. Actually, the regioselective couplings promoted by enzymes are a common occurrence in nature. Herein, we have developed simple, efficient and general transition metal-free intramolecular couplings of alphatic and aromatic C H bonds. The protocol uses readily available aryl triazene as the radical initiator, cheap K2S2O8 as the oxidant, and the couplings were performed well with excellent tolerance of functional groups. Interestingly, alpha-carbon configuration of some amino acid residues in the substrates was kept after the reactions, and the couplings for substrates with substituted phenylalanine residues exhibited complete beta-carbon diastereoselectivity for induction of the chiral alpha-carbon. Therefore, the present study should provide a novel strategy for regioselective cross-dehydrogenative couplings of two different C-H bonds. PMID- 26822837 TI - Predictive factors of mortality and deterioration in performance of activities of daily living after hip fracture surgery in Kagoshima, Japan. AB - AIM: Given that different hospitals achieve different outcomes, optimal evaluation of treatment outcomes in the local community requires evaluation of many institutions in that area. We carried out a prospective multicenter cohort study in Kagoshima Prefecture to identify factors that contribute to deterioration in activities of daily living performance and patient mortality 1 year after surgical treatment of hip fractures. METHODS: We prospectively enrolled 387 patients who underwent surgery for hip fractures in 33 registered facilities within a 6-month period from February to July 2007. Logistic regression analysis was carried out to identify factors that contribute to deterioration in activities of daily living performance and death within 1 year after surgery. RESULTS: An increased risk of Barthel Index (BI) deterioration was associated with increased age (P for trend = 0.003), worse pre-injury BI (P for trend = 0.021), trochanteric fractures (OR 2.07, 95% CI 1.31-3.27), worse BI at discharge (P for trend < 0.001) and postoperatively developed cognitive impairment (OR 6.34, 95% CI 2.15-18.7). The OR for BI deterioration in patients with newly-diagnosed disease after discharge was approximately 9.16 (95% CI 4.03 20.8). No factors except age and sex were statistically significant as the preoperative indicators of mortality risk. Only BI at discharge was a significant determinant of mortality risk (P for trend = 0.013) after adjusting for the effects of age and sex. CONCLUSIONS: Patients with poor activities of daily living performance at the time of hospital discharge were likely to show poor functional recovery and a high 1-year postoperative mortality. Geriatr Gerontol Int 2017; 17: 391-401. PMID- 26822838 TI - The Synthesis of Both Diastereomers of 5'-Methylhomoaristeromycin. AB - The preparation of the C-5' diastereomers of 5'-homoaristeromycin has been achieved in 6 steps beginning with readily available (3aR,6aR)-2,2-dimethyl 2H,3aH,4H,6aH-cyclopenta[1,3]dioxol-4-one in a Michael reaction employing chiral Evans N-acyloxazolidinones that served to direct the requisite side chain stereochemistry. The two targets were evaluated against a battery of viruses and found to possess activity only towards yellow fever. Both compounds were non cytotoxic. PMID- 26822839 TI - Sequencing ebola and marburg viruses genomes using microarrays. AB - Periodic outbreaks of Ebola and Marburg hemorrhagic fevers have occurred in Africa over the past four decades with case fatality rates reaching as high as 90%. The latest Ebola outbreak in West Africa in 2014 raised concerns that these infections can spread across continents and pose serious health risks. Early and accurate identification of the causative agents is necessary to contain outbreaks. In this report, we describe sequencing-by-hybridization (SBH) technique using high density microarrays to identify Ebola and Marburg viruses. The microarrays were designed to interrogate the sequences of entire viral genomes, and were evaluated with three species of Ebolavirus (Reston, Sudan, and Zaire), and three strains of Marburgvirus (Angola, Musoke, and Ravn). The results showed that the consensus sequences generated with four or more hybridizations had 92.1-98.9% accuracy over 95-99% of the genomes. Additionally, with SBH microarrays it was possible to distinguish between different strains of the Lake Victoria Marburgvirus. J. Med. Virol. 88:1303-1308, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26822844 TI - How Often Does Femoroacetabular Impingement Occur After an Innominate Osteotomy for Acetabular Dysplasia? AB - BACKGROUND: Femoroacetabular impingement is increasingly recognized as a cause of hip pain but its incidence after an innominate osteotomy for the correction of acetabular dysplasia has not been determined. This information would be essential for the orthopaedic surgeon because it has the potential to produce a poor outcome in the long term when trying to balance acetabular instability and overcorrection. QUESTIONS/PURPOSES: The purposes of our study were (1) to determine the frequency with which clinically relevant femoroacetabular impingement (FAI) occurs after an innominate osteotomy for the treatment of acetabular dysplasia; (2) to determine risk factors for the development of FAI; and (3) to compare postoperative radiographic and clinical outcomes in patients having undergone an innominate osteotomy for the correction of acetabular dysplasia both with and without FAI. METHODS: This was a retrospective review of 154 hips (132 patients) that had undergone an innominate osteotomy for acetabular dysplasia and were evaluated at a minimum followup of 10 years (mean = 12 years). Mean age at the time of surgery was 3 years, 114 hips had a concomitant open reduction, and 54 hips also had femoral shortening. One hundred eight hips had a Salter osteotomy and 46 had a Pemberton osteotomy. Radiographs were analyzed to determine the lateral center-edge angle (CE angle) and the presence of a crossover sign. The diagnosis of FAI was established when the CE angle was greater than 40 degrees , there was a positive crossover sign, and the patient had groin pain when flexing the hip less than 90 degrees . Comparisons between nonparametric variables were performed with a Mann-Whitney's U test. Categorical variables were compared with a chi-square test. Change in acetabular index (correction) was dichotomized considering 20 degrees of correction as the cutoff point. Association is presented as odds ratio (95% confidence interval), and logistic regression was performed. RESULTS: According to our criteria, 18 of 154 hips had FAI (12%). Of the 18 patients with FAI, 10 had undergone a Pemberton osteotomy (10 of 46 [22%]) and eight a Salter osteotomy (eight of 108 [7%]). A change in the postoperative acetabular index greater than 20 degrees was associated with a greater likelihood of developing FAI. The mean postoperative acetabular index was lower for the group with FAI, for whom it was 20 degrees , compared with the group without FAI, for whom it was 27 degrees (p = 0.04). The mean Iowa Hip Score for the group with FAI was 85, whereas for those without FAI, it was 93 (p = 0.03). CONCLUSIONS: FAI is not common after an innominate osteotomy for the treatment of acetabular dysplasia; however, overcorrection is related to a higher incidence. When FAI is present, it can affect the outcome. Overcorrection should be avoided when performing an innominate osteotomy for the treatment of acetabular dysplasia because it can create iatrogenic FAI and have an adverse effect on outcome. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 26822845 TI - Excessive volume of hydrogel injectates may compromise the efficacy for the treatment of acute myocardial infarction. AB - Biomaterial injectates are promising as a therapy for myocardial infarction to inhibit the adverse ventricular remodeling. The current study explored interrelated effects of injectate volume and infarct size on treatment efficacy. A finite element model of a rat heart was utilized to represent ischemic infarcts of 10%, 20%, and 38% of left ventricular wall volume and polyethylene glycol hydrogel injectates of 25%, 50%, and 75% of the infarct volume. Ejection fraction was 49.7% in the healthy left ventricle and 44.9%, 46.4%, 47.4%, and 47.3% in the untreated 10% infarct and treated with 25%, 50%, and 75% injectate, respectively. Maximum end-systolic infarct fiber stress was 41.6, 53.4, 44.7, 44.0, and 45.3 kPa in the healthy heart, the untreated 10% infarct, and when treated with the three injectate volumes, respectively. Treating the 10% and 38% infarcts with the 25% injectate volume reduced the maximum end-systolic fiber stress by 16.3% and 34.7% and the associated strain by 30.2% and 9.8%, respectively. The results indicate the existence of a threshold for injectate volume above which efficacy does not further increase but may decrease. The efficacy of an injectate in reducing infarct stress and strain changes with infarct size. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26822847 TI - Aspirations and Strategies for Public Health. PMID- 26822846 TI - Comparative repair capacity of knee osteochondral defects using regenerated silk fiber scaffolds and fibrin glue with/without autologous chondrocytes during 36 weeks in rabbit model. AB - The reconstruction capability of osteochondral (OCD) defects using silk-based scaffolds has been demonstrated in a few studies. However, improvement in the mechanical properties of natural scaffolds is still challengeable. Here, we investigate the in vivo repair capacity of OCD defects using a novel Bombyx mori silk-based composite scaffold with great mechanical properties and porosity during 36 weeks. After evaluation of the in vivo biocompatibility and degradation rate of these scaffolds, we examined the effectiveness of these fabricated scaffolds accompanied with/without autologous chondrocytes in the repair of OCD lesions of rabbit knees after 12 and 36 weeks. Moreover, the efficiency of these scaffolds was compared with fibrin glue (FG) as a natural carrier of chondrocytes using parallel clinical, histopathological and mechanical examinations. The data on subcutaneous implantation in mice showed that the designed scaffolds have a suitable in vivo degradation rate and regenerative capacity. The repair ability of chondrocyte-seeded scaffolds was typically higher than the scaffolds alone. After 36 weeks of implantation, most parts of the defects reconstructed by chondrocytes-seeded silk scaffolds (SFC) were hyaline-like cartilage. However, spontaneous healing and filling with a scaffold alone did not eventuate in typical repair. We could not find significant differences between quantitative histopathological and mechanical data of SFC and FGC. The fabricated constructs consisting of regenerated silk fiber scaffolds and chondrocytes are safe and suitable for in vivo repair of OCD defects and promising for future clinical trial studies. PMID- 26822848 TI - Telomeric length heterogeneity influences spontaneous regression of malignant melanoma. PMID- 26822849 TI - First report of imported case of dengue fever in Republic of Serbia. PMID- 26822850 TI - Numerical simulations of the role of a ferroelectric polymer interfacial layer in organic solar cells. AB - A Pauli master equation method is adopted for the simulation of polymer bulk heterojunction (BHJ) solar cells with vinylidene fluoride-trifluoroethylene copolymer (P(VDF-TrFE)) films as interfacial layers. According to previous reports, using highly crystalline P(VDF-TrFE) films as interfacial layers can highly enhance the efficiency of polymer BHJ solar cells, and possible mechanisms for the enhancement by two different groups were given as the dipole induced permanent internal electric field or simply the electrode improvement which implied that the origin is the barrier lowering effect. The correlation between the appearance of S-shaped current density-voltage (J-V) characteristics and the energy barrier is studied first, and then further results indicate that the previous electrode improvement model provides a consistent explanation for the origin of performance enhancement due to the insertion of polarized P(VDF-TrFE) interfacial layers. Moreover, the phenomenon of an increase of the internal electric field observed before can be attributed to better contact conditions which help reduce the bimolecular recombination rate. Comparatively speaking, the electrode improvement model can give a more rational explanation for the origin of performance enhancement experimentally found. In contrast, the dipole induced permanent internal electric field model was not complete enough. PMID- 26822851 TI - Erratum: Intracellular amyloid beta oligomers impair organelle transport and induce dendritic spine loss in primary neurons. AB - The original version of this article unfortunately contained a mistake in the presentation of Fig. 1 in both the PDF and HTML versions of this manuscript [1]. In the right panel of the corrected Fig. 1d, the images of Mock cells, which were visualized with GFP and stained with Abeta oligomer-specific antibody 11A1, were replaced with those of APPWT cells, and instead the images of APPWT cells were replaced with those of Mock cells. These images had been incorrectly placed in the original Fig. 1. The correct version of Fig. 1 is presented below. PMID- 26822852 TI - Next-generation sequencing confirms the implication of SLC24A1 in autosomal recessive congenital stationary night blindness. AB - Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous retinal disorder which represents rod photoreceptor dysfunction or signal transmission defect from photoreceptors to adjacent bipolar cells. Patients displaying photoreceptor dysfunction show a Riggs-electroretinogram (ERG) while patients with a signal transmission defect show a Schubert-Bornschein ERG. The latter group is subdivided into complete or incomplete (ic) CSNB. Only few CSNB cases with Riggs-ERG and only one family with a disease-causing variant in SLC24A1 have been reported. Whole-exome sequencing (WES) in a previously diagnosed icCSNB patient identified a homozygous nonsense variant in SLC24A1. Indeed, re-investigation of the clinical data corrected the diagnosis to Riggs form of CSNB. Targeted next-generation sequencing (NGS) identified compound heterozygous deletions and a homozygous missense variant in SLC24A1 in two other patients, respectively. ERG abnormalities varied in these three cases but all patients had normal visual acuity, no myopia or nystagmus, unlike in Schubert Bornschein-type of CSNB. This confirms that SLC24A1 defects lead to CSNB and outlines phenotype/genotype correlations in CSNB subtypes. In case of unclear clinical characteristics, NGS techniques are helpful to clarify the diagnosis. PMID- 26822853 TI - Extremely Weak van der Waals Coupling in Vertical ReS2 Nanowalls for High-Current Density Lithium-Ion Batteries. AB - The synthesis of vertical ReS2 nanowalls on 3D graphene foam (V-ReS2 /3DGF) is demonstrated by a chemical vapor deposition route. The vertical nanowall structure leads to an effective exposure of active sites and enhances the lithium interaction with all of the layers. When serving as the anode material for lithium-ion batteries, the V-ReS2 /3DGF composite demonstrates excellent cycling stability at high-current-density. PMID- 26822854 TI - Correlation structure and variable selection in generalized estimating equations via composite likelihood information criteria. AB - The method of generalized estimating equations (GEE) is popular in the biostatistics literature for analyzing longitudinal binary and count data. It assumes a generalized linear model for the outcome variable, and a working correlation among repeated measurements. In this paper, we introduce a viable competitor: the weighted scores method for generalized linear model margins. We weight the univariate score equations using a working discretized multivariate normal model that is a proper multivariate model. Because the weighted scores method is a parametric method based on likelihood, we propose composite likelihood information criteria as an intermediate step for model selection. The same criteria can be used for both correlation structure and variable selection. Simulations studies and the application example show that our method outperforms other existing model selection methods in GEE. From the example, it can be seen that our methods not only improve on GEE in terms of interpretability and efficiency but also can change the inferential conclusions with respect to GEE. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26822855 TI - Mechanism of Residual Lumen Stenosis at the Side Branch Ostium After Final Kissing Balloon Inflation: A Volumetric Intracoronary Ultrasound Study of Coronary Bifurcation Lesions. AB - OBJECTIVES: To investigate the mechanisms of residual stenosis (RS) at side branch ostium (SBO) after final kissing balloon inflation (FKI) and clarify the impact of carina- and plaque-shifts on RS. BACKGROUND: Carina- and plaque-shift induce SBO compromise. FKI is an effective technique to treat this complication; however, RS often persist, and are associated with restenosis at SBO. METHODS: We performed serial volumetric analysis of 91 bifurcations in which crossover stenting with FKI and pre-/post-intravascular ultrasounds (IVUS) were completed in both branches. The plaque- and carina-shifts were defined as an increase in the plaque-volume and a decrease in the vessel-volume at the SBO, respectively. RS at the SBO, defined as area stenosis >50% on IVUS, was identified in 19 lesions. RESULTS: After FKI, the plaque volume- significantly increased at the SBO, with its reduction in the proximal main vessel (MV). However, at the SBO, the volumetric lumen change correlated with vessel change (rho = 0.690, P < 0.001), but not plaque change (P = 0.390), suggesting that RS at SBO was more likely associated with inadequate vessel stretch, not plaque increase after FKI. Carina-shift was more frequently found in cases with RS, compared to those without RS (37% vs. 11%, P = 0.013). Pre-procedure IVUS findings to predict RS at SBO after FKI were negative-remodeling at distal MV, plaque -burden at distal MV, and plaque-burden at the SBO. CONCLUSIONS: Carina-shift has a greater contribution to the formation of RS at SBO after FKI. The pre-procedure IVUS provides helpful information for predicting the RS after FKI. PMID- 26822856 TI - Emergence of core-peripheries in networks. AB - A number of important transport networks, such as the airline and trade networks of the world, exhibit a characteristic core-periphery structure, wherein a few nodes are highly interconnected and the rest of the network frays into a tree. Mechanisms underlying the emergence of core-peripheries, however, remain elusive. Here, we demonstrate that a simple pruning process based on removal of underutilized links and redistribution of loads can lead to the emergence of core peripheries. Links are assumed beneficial if they either carry a sufficiently large load or are essential for global connectivity. This incentivized redistribution process is controlled by a single parameter, which balances connectivity and profit. The obtained networks exhibit a highly resilient and connected core with a frayed periphery. The balanced network shows a higher resilience than the world airline network or the world trade network, revealing a pathway towards robust structural features through pruning. PMID- 26822857 TI - Hydrogen Bonds Dictate the Coordination Geometry of Copper: Characterization of a Square-Planar Copper(I) Complex. AB - 6,6''-Bis(2,4,6-trimethylanilido)terpyridine (H2Tpy(NMes)) was prepared as a rigid, tridentate pincer ligand containing pendent anilines as hydrogen bond donor groups in the secondary coordination sphere. The coordination geometry of (H2 Tpy(NMes))copper(I)-halide (Cl, Br and I) complexes is dictated by the strength of the NH-halide hydrogen bond. The Cu(I)Cl and Cu(II)Cl complexes are nearly isostructural, the former presenting a highly unusual square-planar geometry about Cu(I) . The geometric constraints provided by secondary interactions are reminiscent of blue copper proteins where a constrained geometry, or entatic state, allows for extremely rapid Cu(I)/Cu(II) electron transfer self-exchange rates. Cu(H2 Tpy(NMes))Cl shows similar fast electron transfer (~10(5) m(-1) s(-1)) which is the same order of magnitude as biological systems. PMID- 26822859 TI - Scale morphometry allows discrimination of European sardine Sardina pilchardus and round sardinella Sardinella aurita and among their local populations. AB - Landmark-based geometric morphometric analysis revealed differences in scale shape between European sardine Sardina pilchardus and round sardinella Sardinella aurita as well as among the local populations of each species. Fish scale measurements from four different areas in the central and eastern Mediterranean Sea showed that the mean scale shape of the two species using landmark data could be differentiated with high certainty. Populations of S. aurita from the central and eastern Mediterranean Sea could be separated reliably (P < 0.001) with an average discrimination rate of 91%, whereas the average discrimination of the S. pilchardus populations was lower (80%), albeit still high. PMID- 26822858 TI - High glucose-induced hyperosmolarity contributes to COX-2 expression and angiogenesis: implications for diabetic retinopathy. AB - BACKGROUND: We tested the hypothesis that glucose-induced hyperosmolarity, occurring in diabetic hyperglycemia, promotes retinal angiogenesis, and that interference with osmolarity signaling ameliorates excessive angiogenesis and retinopathy in vitro and in vivo. METHODS AND RESULTS: We incubated human aortic (HAECs) and dermal microvascular endothelial cells (HMVECs) with glucose or mannitol for 24 h and tested them for protein levels and in vitro angiogenesis. We used the Ins2 Akita mice as a model of type 1 diabetes to test the in vivo relevance of in vitro observations. Compared to incubations with normal (5 mmol/L) glucose concentrations, cells exposed to both high glucose and high mannitol (at 30.5 or 50.5 mmol/L) increased expression of the water channel aquaporin-1 (AQP1) and cyclooxygenase (COX)-2. This was preceded by increased activity of the osmolarity-sensitive transcription factor Tonicity enhancer binding protein (TonEBP), and enhanced endothelial migration and tubulization in Matrigel, reverted by treatment with AQP1 and TonEBP siRNA. Retinas of Ins2 Akita mice showed increased levels of AQP1 and COX-2, as well as angiogenesis, all reverted by AQP1 siRNA intravitreal injections. CONCLUSIONS: Glucose-related hyperosmolarity seems to be able to promote angiogenesis and retinopathy through activation of TonEBP and possibly increasing expression of AQP1 and COX-2. Osmolarity signaling may be a target for therapy. PMID- 26822860 TI - Modernization of AOAC Nutrient Methods by Stakeholder Panel on Infant Formula and Adult Nutritionals. AB - Infant formula is one of the most highly regulated products in the world. To comply with global regulations and to ensure the products are manufactured within product specifications, accurate analytical testing is required. Most of the AOAC INTERNATIONAL legacy test methods for infant formula were developed and validated in the 1980s and 1990s. Although these methods performed very well for many years, infant formulas have been updated, and today's products contain many new and novel ingredients. There were a number of cases in which the legacy AOAC methods began to result in problems with the analysis of modern infant formulas, and the use of these methods caused some disputes with regulatory agencies. In 2010, AOAC reached an agreement with the International Formula Council, which has changed its name to the Infant Nutrition Council of America, regarding a project to modernize these AOAC infant-formula test methods. This agreement led to the development of Standard Method Performance Requirements (SMPRs((r))) for 28 nutrients. After SMPR approval, methods were collected, evaluated, validated, and approved through the AOAC Official Methods(SM) process. Forty-seven methods have been approved as AOAC First Action Methods, and eight have been approved as Final Action. PMID- 26822861 TI - Ketamine exposure during embryogenesis inhibits cellular proliferation in rat fetal cortical neurogenic regions. AB - BACKGROUND: Developmental neurotoxicity of ketamine, an N-methyl-D-aspartate receptor antagonist, must be considered due to its widespread uses for sedation/analgesia/anesthesia in pediatric and obstetric settings. Dose-dependent effects of ketamine on cellular proliferation in the neurogenic regions of rat fetal cortex [ventricular zone (VZ) and subventricular zone (SVZ)] were investigated in this in vivo study. METHODS: Timed-pregnant Sprague-Dawley rats at embryonic day 17 (E17) were given with different doses of ketamine intraperitoneally (0, 1, 2, 10, 20, 40, and 100 mg/kg). Proliferating cells in the rat fetal brains were labeled by injecting 100 mg/kg of 5-bromo-2' deoxyuridine (BrdU) intraperitoneally. BrdU-labeled cells were detected by immunostaining methods. The numbers of BrdU-positive cells in VZ and SVZ of rat fetal cortex were employed to quantify proliferation in the developing rat cortex. RESULTS: Ketamine dose-dependently reduced the number of BrdU-positive cells in VZ (P < 0.001) and SVZ (P < 0.001) of the rat fetal cortex. SVZ showed greater susceptibility to ketamine-induced reduction of proliferation in rat fetal cortex, occurring even at clinically relevant doses (2 mg/kg). CONCLUSION: These data suggest that exposure to ketamine during embryogenesis can dose dependently inhibit the cellular proliferation in neurogenic regions of the rat fetal cortex. PMID- 26822862 TI - Capturing the wide variety of impaired fracture healing phenotypes in Neurofibromatosis Type 1 with eight key factors: a computational study. AB - Congenital pseudarthrosis of the tibia (CPT) is a rare disease which normally presents itself during early childhood by anterolateral bowing of the tibia and spontaneous tibial fractures. Although the exact etiology of CPT is highly debated, 40-80% of CPT patients are carriers of a mutation in the Neurofibromatosis Type 1 (NF1) gene, which can potentially result in an altered phenotype of the skeletal cells and impaired bone healing. In this study we use a computational model of bone regeneration to examine the effect of the Nf1 mutation on bone fracture healing by altering the parameter values of eight key factors which describe the aberrant cellular behaviour of Nf1 haploinsufficient and Nf1 bi-allelically inactivated cells. We show that the computational model is able to predict the formation of a hamartoma as well as a wide variety of CPT phenotypes through different combinations of altered parameter values. A sensitivity analysis by "Design of Experiments" identified the impaired endochondral ossification process and increased infiltration of fibroblastic cells as key contributors to the degree of severity of CPT. Hence, the computational model results have added credibility to the experimental hypothesis of a genetic cause (i.e. Nf1 mutation) for CPT. PMID- 26822863 TI - An improved approach for predicting drug-target interaction: proteochemometrics to molecular docking. AB - Proteochemometric (PCM) methods, which use descriptors of both the interacting species, i.e. drug and the target, are being successfully employed for the prediction of drug-target interactions (DTI). However, unavailability of non interacting dataset and determining the applicability domain (AD) of model are a main concern in PCM modeling. In the present study, traditional PCM modeling was improved by devising novel methodologies for reliable negative dataset generation and fingerprint based AD analysis. In addition, various types of descriptors and classifiers were evaluated for their performance. The Random Forest and Support Vector Machine models outperformed the other classifiers (accuracies >98% and >89% for 10-fold cross validation and external validation, respectively). The type of protein descriptors had negligible effect on the developed models, encouraging the use of sequence-based descriptors over the structure-based descriptors. To establish the practical utility of built models, targets were predicted for approved anticancer drugs of natural origin. The molecular recognition interactions between the predicted drug-target pair were quantified with the help of a reverse molecular docking approach. The majority of predicted targets are known for anticancer therapy. These results thus correlate well with anticancer potential of the selected drugs. Interestingly, out of all predicted DTIs, thirty were found to be reported in the ChEMBL database, further validating the adopted methodology. The outcome of this study suggests that the proposed approach, involving use of the improved PCM methodology and molecular docking, can be successfully employed to elucidate the intricate mode of action for drug molecules as well as repositioning them for new therapeutic applications. PMID- 26822864 TI - Studies comparing ambulatory blood pressure and home blood pressure on cardiovascular disease and mortality outcomes: a systematic review. AB - Ambulatory blood pressure monitoring (ABPM) is more commonly recommended for assessing out-of-clinic blood pressure (BP) than home blood pressure monitoring (HBPM). We conducted a systematic review to examine whether ABPM or HBPM is more strongly associated with cardiovascular disease events and/or mortality. Of 1007 abstracts published through July 20, 2015, nine articles, reporting results from seven cohorts, were identified. After adjustment for BP on HBPM, BP on ABPM was associated with an increased risk of outcomes in two of four cohorts for systolic blood pressure and two of three cohorts for diastolic blood pressure. After adjustment for BP on ABPM, systolic blood pressure on HBPM was associated with outcomes in zero of three cohorts; an association was present in one of two cohorts for diastolic blood pressure on HBPM. There is a lack of strong empiric evidence supporting ABPM or HBPM over the other approach for predicting cardiovascular events or mortality. PMID- 26822865 TI - Maternal and child reflective functioning in the context of child sexual abuse: pathways to depression and externalising difficulties. AB - BACKGROUND: Sexual abuse is a well-recognised risk factor for child psychopathology. Little is known regarding whether child and maternal mentalization can be considered a potential resource or protective factor in this context, respectively, mediating or moderating the relationship between sexual abuse and psychopathology. OBJECTIVE: The aims of this study were (1) to explore the relationships between child and maternal mentalizing, measured as reflective functioning (RF), and child depressive symptoms and externalising difficulties; and (2) to examine whether child mentalizing mediates the relationship between child sexual abuse (CSA) and psychopathology. METHOD: A total of 168 children aged 7-12 years and their mothers participated in the study. The sample included 74 dyads where children had experienced sexual abuse. The Child Attachment Interview was rated by using the Child Reflective Functioning Scale to assess children's mentalization, and the Child Depression Inventory was used to assess depressive symptoms. Mothers completed the Parent Development Interview to assess maternal RF and the Child Behavior Checklist to assess their child's externalising difficulties. A model involving direct and indirect paths from CSA, child and maternal RF to child psychopathology was examined using Mplus software. RESULTS: Child mentalization partially mediated the relationships between CSA and depressive symptoms, as well as the relationship between CSA and externalising difficulties. Maternal mentalization was an independent predictor of child externalising difficulties, with higher maternal RF associated with less externalising difficulties. DISCUSSION: The findings indicate that by ages 7-12, child mentalization is an important inner resource associated with lower depression and externalising. In addition, this study provides new evidence of the importance of the parent's mentalizing stance for the development of self regulation and externalising difficulties in both abused and non-abused children. The clinical implications are discussed. PMID- 26822866 TI - A Highly Ion-Selective Zeolite Flake Layer on Porous Membranes for Flow Battery Applications. AB - Zeolites are crystalline microporous aluminosilicates with periodic arrangements of cages and well-defined channels, which make them very suitable for separating ions of different sizes, and thus also for use in battery applications. Herein, an ultra-thin ZSM-35 zeolite flake was introduced onto a poly(ether sulfone) based porous membrane. The pore size of the zeolite (ca. 0.5 nm) is intermediary between that of hydrated vanadium ions (>0.6 nm) and protons (<0.24 nm). The resultant membrane can thus be used to perfectly separate vanadium ions and protons, making this technology useful in vanadium flow batteries (VFB). A VFB with a zeolite-coated membrane exhibits a columbic efficiency of >99 % and an energy efficiency of >81 % at 200 mA cm(-2), which is by far the highest value ever reported. These convincing results indicate that zeolite-coated membranes are promising in battery applications. PMID- 26822867 TI - Erratum to: Radiation-induced miR-208a increases the proliferation and radioresistance by targeting p21 in human lung cancer cells. PMID- 26822868 TI - Using Key Distance to Clarify a Theory on the SNARC. AB - The most prominent explanation for the spatial numerical association of response codes (SNARC) effect is the direct mapping account (DMA). The DMA assumes that (a) numbers are represented on a mental number line, (b) this mental number line is mapped to external space, and (c) the better the mapping location corresponds to the response location, the faster the response. The DMA leaves open whether a variation of response locations can (ceteris paribus) influence the location to which numbers are mapped in external space. In order to investigate this question, we varied response key distance during a standard parity judgment and a magnitude judgment task. We found that even drastic manipulations of response key distance did not modulate the SNARC effect. Power and meta-analyses show that this null effect is not due to insufficient statistical power or a poor experimental setup. Thus, our results indicate that, in order for the DMA to explain the SNARC effect, it must assume that the mapping from the mental number line to external space is anchored to response location. For future research, our results suggest that it is not necessary to control the horizontal separation of the response keys in basic SNARC experiments. PMID- 26822869 TI - Experimental measurement of preferences in health care using best-worst scaling (BWS): theoretical and statistical issues. AB - For optimal solutions in health care, decision makers inevitably must evaluate trade-offs, which call for multi-attribute valuation methods. Researchers have proposed using best-worst scaling (BWS) methods which seek to extract information from respondents by asking them to identify the best and worst items in each choice set. While a companion paper describes the different types of BWS, application and their advantages and downsides, this contribution expounds their relationships with microeconomic theory, which also have implications for statistical inference. This article devotes to the microeconomic foundations of preference measurement, also addressing issues such as scale invariance and scale heterogeneity. Furthermore the paper discusses the basics of preference measurement using rating, ranking and stated choice data in the light of the findings of the preceding section. Moreover the paper gives an introduction to the use of stated choice data and juxtaposes BWS with the microeconomic foundations. PMID- 26822870 TI - Potential biological efficacy of Pinus plant species against oxidative, inflammatory and microbial disorders. AB - BACKGROUND: Traditionally, Pine has been used to treat oxidative and inflammatory disorders. The study was aimed to investigate biological potential of phytoconstituents of Pinus plant species: Pinus roxburghii, Pinus wallichiana and Pinus gerardiana using in-vitro antioxidant, anti-inflammatory and antimicrobial methods. METHOD: The hydro-alcoholic extraction of dried plant: stem bark was done and the antioxidant activity was evaluated using free radical scavenging methods for 1,1-diphenyl-2-picrylhydrazyl, (DPPH), nitric oxide and hydrogen peroxide radicals, reducing power assays, and total antioxidant capacity. Anti inflammatory activity was carried out using albumin denaturation and HRBC membrane stabilization assays. Antimicrobial and antifungal activities were also conducted using agar well diffusion method. RESULTS: The qualitative phytochemical analysis of hydro-alcoholic stem bark extracts of three plant species revealed the presence of various biochemical compounds such as alkaloids, flavonoids, glycosides, triterpenoids and saponins. Quantitative phytochemical analysis of plant extracts showed the presence of phenolics, flavonoids, tannins, beta-carotene and lycopene. Plant extracts of three pinus species showed significant antioxidant activity against DPPH, nitric oxide and H2O2 radicals. In in-vitro anti-inflammatory investigation, Pinus roxburghii exhibited highest protection against albumin denaturation 86.54 +/- 1.85 whereas Pinus gerardiana showed 82.03 +/- 2.67. Moreover, plant extracts were found to prevent the growth of microorganisms Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Candida albicans showing promising antibacterial and antifungal activities againstCandida albicans. CONCLUSION: The findings of the present study derived the rational for the therapeutic usage of Pinus which is a highly timber yielding plant from Himalayan region, against oxidative, inflammatory and microbial diseases. PMID- 26822871 TI - Polymorphisms of the FOXF1 and MHC locus genes in individuals undergoing esophageal acid reflux assessments. AB - Gastroesophageal reflux disease (GERD) may lead to Barrett's esophagus (BE). Previously, a large genome-wide association study found two germline markers to be associated with BE, FOXF1 rs9936833 (C allele) and MHC rs9257809 (A allele). This study evaluated whether these two polymorphisms are associated with gastroesphageal acid reflux as measured by 24-hour pH testing. Patients with acid reflux symptoms referred for esophageal manometry and 24-hour pH monitoring at University Health Network (Toronto, ON) were enrolled. DNA extracted from blood was genotyped using a Taqman Polymerase Chain Reaction (PCR) assay. DeMeester scores of >=14.7 or prior evidence of reflux esophagitis on endoscopy defined individuals with esophageal acid reflux. Logistic regression analysis, adjusted for clinical risk factors, was used to calculate odds ratios with 95% confidence intervals for each polymorphism in relation to the presence of acid reflux. Of 182 patients, the median age was 50 years and 62% were female; 95 (52%) met the definition of GERD. In the multivariable analysis, both FOXF1 rs9936833 (OR = 1.82; 95%CI: 1.12-2.96; P = 0.02) and MHC rs9257809 (OR = 9.36; 95%CI: 2.92 29.99; P < 0.001) remained significantly associated with presence of acid reflux. When both polymorphisms were placed in the same model, the adjusted ORs were 2.10 (95%CI: 1.24-3.53; P = 0.005) and 10.95 (95%CI: 3.32-36.09; P < 0.001), respectively. The association for risk allele C in FOXF1 rs9936833 and risk allele A in MHC rs9257809 with the presence of acid reflux suggests a potential pathophysiologic mechanism for the role of genetic influences in BE development. PMID- 26822872 TI - Efficacy of progesterone supplementation during early pregnancy in cows: A meta analysis. AB - Progesterone is a critical hormone during early pregnancy in the cow. As a result, a number of studies have investigated the effects of progesterone supplementation on pregnancy rates. In this study, a meta-analysis using a univariate binary random effects model was carried out on 84 specific treatments reported in 53 publications involving control (n = 9905) and progesterone-treated (n = 9135) cows. Although the results of individual studies showed wide variations (-40% to +50% point changes), progesterone treatment resulted in an overall increase in pregnancy rate odds ratio (OR = 1.12; P < 0.01). Improvements in pregnancy rate were only observed in cows treated at natural estrus (OR = 1.41, P < 0.01) and not following synchronization of estrus or ovulation. Although treatment between Days 3 to 7 postinsemination was beneficial (OR = 1.15; P < 0.01), treatment earlier or later than this was not. Progesterone supplementation was beneficial in cows of lower fertility (<45% control pregnancy rate) but not in cows with higher fertility. These results indicated that the benefit of progesterone supplementation on fertility of cows required exogenous progesterone supplementation to start between Day 3 to 7 and the appropriate reproductive status (i.e., lower fertility, natural estrus) of the treated cows. PMID- 26822874 TI - Expression of Penaeus monodon ortholog of Niemann-Pick type C-2 in the spermatic tract, and its role in sperm cholesterol removal. AB - Protein and lipid composition of sperm plasma membrane are modified as these gametes continue to mature during their transit along the spermatic tract. Our previous study revealed that during its journey through the spermatic duct of the black tiger prawn, Penaeus monodon, sperm cholesterol content decreases through the action of lipid-binding proteins within the luminal environment. In this study, the full cDNA sequence of epididymal secretory protein E1 (HE1), or Niemann-Pick C2 (NPC2), was cloned from P. monodon (termed Pmnpc2), and its conserved cholesterol/lipid-binding domain was characterized. The putative tertiary structure of PmNPC2 showed high similarity with the structure of Bos taurus NPC2. Pmnpc2 is expressed in many tissues, including the spermatic tract (i.e., testis, vas deferens, terminal ampoule) and the female thelycum. In situ hybridization revealed the presence of Pmnpc2 transcripts in the vas deferens, terminal ampoule, and thelycum epithelia, suggesting that PmNPC2 could be secreted into the lumen of the spermatic duct. A recombinant hexahistidine-tagged PmNPC2 (rPmNPC2-6His) was able to bind cholesterol and sperm lipid extracts, while co-incubation of sperm from the vas deferens with rPmNPC2-6His resulted in the depletion of cholesterol from these gametes. Together, these results suggest that PmNPC2 participates in sperm cholesterol efflux during the sperm maturation process in P. monodon. Mol. Reprod. Dev. 83: 259-270, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26822875 TI - Erratum: Dynamic changes in host gene expression associated with H5N8 avian influenza virus infection in mice. PMID- 26822876 TI - Femoral facial syndrome associated with a de novo complex chromosome 2q37 rearrangement. AB - The femoral facial syndrome (FFS) is a rare congenital anomaly syndrome characterized by bilateral femoral hypoplasia and facial dysmorphism. The etiology of FFS is currently unknown but maternal/gestational diabetes has been proposed as a strong risk factor for syndromic femoral hypoplasia. In affected children born to non-diabetic mothers, a genetic contribution to FFS is suspected; however, no chromosomal anomalies or gene mutations have been identified so far. Here, we report on a girl with FFS and a de novo complex chromosome rearrangement of terminal chromosome 2q37.2. Radiographs of the pelvis and lower limbs showed bilateral shortening and bowing of the femur and radiographs of hands and feet revealed a brachydactyly type E (BDE). Using high resolution array-CGH, qPCR, and FISH, we detected a ~1.9 Mb duplication in the chromosomal region 2q37.2 and a ~5.4 Mb deletion on chromosome 2q37.3 that were absent in the parents. The duplication contains six genes and the deletion encompasses 68 genes; the latter has previously been shown to cause BDE (through haploinsufficiency for HDAC4) but not femoral hypoplasia. Therefore, we propose that the duplication 2q37.2 could be causative for the femur phenotype. To the best of our knowledge, our report is the first to propose a genetic cause in a case of FFS. PMID- 26822877 TI - Building a hit list for the fight against metastatic castration resistant prostate cancer. AB - Identification of genetic alterations in Metastatic Castration Resistant Prostate Cancer (mCRPC) may provide scientists and clinicians with a list of new targets for drug research and development. Recently published in Cell, Robinson et al. present the first look at genetic data from mCRPC lesions gathered over multiple years and from many institutions. PMID- 26822878 TI - Response to Dr Ramiro Manzano Nunez's comments. PMID- 26822879 TI - 2015 James Ewing Lecture: 75-Year History of the Society of Surgical Oncology Part III: The Transformative Years (1991-2015). PMID- 26822880 TI - Development of a Risk Prediction Model to Individualize Risk Factors for Surgical Site Infection After Mastectomy. AB - BACKGROUND: Little data are available regarding individual patients' risk of surgical site infection (SSI) following mastectomy with or without immediate reconstruction. Our objective was to develop a risk prediction model for mastectomy-related SSI. METHODS: Using commercial claims data, we established a cohort of women <65 years of age who underwent a mastectomy from 1 January 2004 31 December 2011. International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes were used to identify SSI within 180 days after surgery. SSI risk factors were determined with multivariable logistic regression using derivation data from 2004-2008 and validated with 2009-2011 data using discrimination and calibration measures. RESULTS: In the derivation cohort, 595 SSIs were identified in 7607 (7.8 %) women, and 396 SSIs were coded in 4366 (9.1 %) women in the validation cohort. Independent risk factors for SSIs included rural residence, rheumatologic disease, depression, diabetes, hypertension, liver disease, obesity, pre-existing pneumonia or urinary tract infection, tobacco use disorder, smoking-related diseases, bilateral mastectomy, and immediate reconstruction. Receipt of home healthcare was associated with lower risk. The model performed equally in the validation cohort per discrimination (C-statistics 0.657 and 0.649) and calibration (Hosmer-Lemeshow p = 0.091 and 0.462 for derivation and validation, respectively). Three risk strata were created based on predicted SSI risk, which demonstrated good correlation with the proportion of observed infections in the strata. CONCLUSIONS: We developed and internally validated an SSI risk prediction model that can be used to counsel women with regard to their individual risk of SSI post-mastectomy. Immediate reconstruction, diabetes, and smoking-related diseases were important risk factors for SSI in this non-elderly population of women undergoing mastectomy. PMID- 26822881 TI - Long-Term Survival Benefit and Potential for Cure after R1 Resection for Colorectal Liver Metastases. AB - BACKGROUND: Although efficient chemotherapy regimens have improved outcomes after R1 resection (positive margins) for colorectal liver metastases (CLMs), the long term survival benefit and potential for cure after R1 resection have not been clearly demonstrated. The aim of this study was to evaluate the long-term outcome after R1 resection for CLM, and to identify factors predictive of cure. METHODS: All resected CLM patients at our institution from 2000 to 2009 were prospectively evaluated. Cure was defined as a disease-free interval >=5 years from the last hepatic or extrahepatic resection to last follow-up. RESULTS: Of 628 patients consecutively resected for CLM, 428 were eligible for the study, of whom 219 (51 %) underwent R0 resection (negative margins) and 209 (49 %) underwent R1 resection. Overall, 130 patients with R0 resection and 141 patients with R1 resection had more than 5 years of follow-up. Five- and 10-year overall survival rates were 56 and 34 % for R0 patients, and 48 and 36 % for R1 patients, respectively (p = 0.37). Of the 141 patients who underwent R1 resection, 26 patients (18 %) were considered 'cured', and 106 patients (75 %) were considered 'noncured'. Independent predictive factors of cure after R1 resection included <=10 total cycles of preoperative chemotherapy and objective response to preoperative chemotherapy. CONCLUSIONS: Overall, potential cure can be achieved in 18 % of patients after R1 resection for CLM. The best conditions to achieve long-term survival after R1 resection rely on a good response to efficient and short first-line chemotherapy. PMID- 26822882 TI - The pattern of lipids and lipoproteins during the menopausal transition in Chinese women. AB - Objective To investigate changes in levels of lipids and lipoproteins in Chinese women during perimenopause and postmenopause as primary study endpoints, for the first time including lipoprotein(a). Methods The retrospective study was performed in 1015 women without hormone therapy aged 34-76 years from 20 provinces of China who visited the Beijing Obstetrics & Gynecology hospital. Menopausal status was defined by the criteria of the 2011 Stages of Reproductive Aging Workshop. Results Levels of total cholesterol, triglycerides and low density lipoprotein (LDL) cholesterol increased and that of high density lipoprotein (HDL) cholesterol decreased in the postmenopausal compared to the perimenopausal group. In the women with body mass index (BMI) >= 25 kg/m(2), total cholesterol and LDL cholesterol increased, HDL cholesterol decreased and changes in triglyceride levels were not significant. In the women with BMI < 25 kg/m(2), the increase in triglyceride levels during the transition was significant. Changes in lipoprotein(a), apolipoprotein A1 and apolipoprotein B were not significant. Comparing the groups with BMI >= 25 kg/m(2) vs. BMI < 25 kg/m(2), only the differences for apolipoprotein A1 and for triglycerides were significant. Triglycerides correlated positively with follicle stimulating hormone and BMI, and total cholesterol correlated positively with follicle stimulating hormone and age (all p < 0.05). Conclusions Some changes in lipids can be related to menopausal status, some to increasing age, some to both; especially triglycerides and apolipoprotein A1 were found also to be related to BMI. Surprisingly lipoprotein(a) did not change either with increasing age or during the transition despite known possible interference with estrogenic status. PMID- 26822884 TI - Screen-printed nanoparticles as anti-counterfeiting tags. AB - Metallic nanoparticles with different physical properties have been screen printed as authentication tags on different types of paper. Gold and silver nanoparticles show unique optical signatures, including sharp emission bandwidths and long lifetimes of the printed label, even under accelerated weathering conditions. Magnetic nanoparticles show distinct physical signals that depend on the size of the nanoparticle itself. They were also screen printed on different substrates and their magnetic signals read out using a magnetic pattern recognition sensor and a vibrating sample magnetometer. The novelty of our work lies in the demonstration that the combination of nanomaterials with optical and magnetic properties on the same printed support is possible, and the resulting combined signals can be used to obtain a user-configurable label, providing a high degree of security in anti-counterfeiting applications using simple commercially-available sensors. PMID- 26822883 TI - Population structure, epidemiology and antibiotic resistance patterns of Streptococcus pneumoniae serotype 5: prior to PCV-13 vaccine introduction in Eastern Gambia. AB - BACKGROUND: Streptococcus pneumoniae serotype 5 is among the most common serotypes causing invasive pneumococcal disease (IPD) in The Gambia. We anticipate that introduction of the 13-valent pneumococcal conjugate vaccine (PCV 13) into routine vaccination in The Gambia will reduce serotype 5 IPD. However, the emergence of new clones that have altered their genetic repertoire through capsular switching or genetic recombination after vaccination with PCV-13 poses a threat to this public health effort. In order to monitor for potential genetic changes post-PCV-13 vaccination, we established the baseline population structure, epidemiology, and antibiotic resistance patterns of serotype 5 before the introduction of PCV-13. METHODS: Fifty-five invasive S. pneumoniae serotype 5 isolates were recovered from January 2009 to August 2011 in a population-based study in the Upper River Region of The Gambia. Serotyping was done by latex agglutination and confirmed by serotype-specific Polymerase Chain Reaction (PCR). Genotyping was undertaken using Multilocus Sequence Typing (MLST). Antimicrobial sensitivity was done using disc diffusion. Contingency table analyses were conducted using Pearson's Chi(2) and Fisher's exact test. Clustering was performed using Bionumerics version 6.5. RESULTS: MLST resolved S. pneumoniae serotype 5 isolates into 3 sequence types (ST), namely ST 289(6/55), ST 3339(19/55) and ST 3404(30/55). ST 289 was identified as the major clonal complex. ST 3339, the prevalent genotype in 2009 [84.6% (11/13)], was replaced by ST 3404 [70.4% (19/27)] in 2010 as the dominant ST. Interestingly, ST 3404 showed lower resistance to tetracycline and oxacillin (P < 0.001), an empirical surrogate to penicillin in The Gambia. CONCLUSIONS: There has been an emergence of ST 3404 in The Gambia prior to the introduction of PCV-13. Our findings provide important background data for future assessment of the impact of PCV-13 into routine immunization in developing countries, such as The Gambia. PMID- 26822885 TI - Determination of Chloride in Infant Formula and Adult/Pediatric Nutritional Formula by Potentiometric Titration: Single-Laboratory Validation, First Action 2015.07. AB - A potentiometric method for determination of chloride was validated against AOAC Standard Method Performance Requirement (SMPR((r))) 2014.015. Ten AOAC Stakeholder Panel on Infant Formula and Adult Nutritionals (SPIFAN) matrixes, including National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 1849a, were tested in duplicate on 6 independent days. The repeatability (RSDr) ranged from 0.43 to 1.34%, and the intermediate reproducibility (RSDiR) ranged from 0.80 to 3.04%. All results for NIST SRM 1849a were within the range of the certified concentration (701 +/- 17 mg/100 g). Recovery was demonstrated with two overspike levels, 50 and 100%, in the 10 SPIFAN matrixes. Samples were tested in duplicate on 3 different days, and all results were within the SMPR requirement of 95 to 105%. The LOQs of the method for powdered products and ready-to-feed or reconstituted products were 20 mg/100 g and 2.2 mg/100 mL, respectively. A wide analytical range from the LOQ to 99.5% chlorine content can be reached with an appropriate dilution factor, but in practice, the upper analytical value observed in routine matrix testing was approximately 1080 mg/100 g in skim milk powder. This is a rapid, simple, and reliable chlorine-testing method applicable to infant formula, adult nutritionals, and ingredients used in these dairy-based products, such as skim milk powder, desalted whey powder, whey protein powder, and whole milk powder. PMID- 26822886 TI - Carcass and meat quality of finished and non-finished Limousin heifers from alpine livestock systems differing in altitudinal origin of the forage. AB - Effects of the alpine origin of the forage and of finishing on carcass and beef quality were quantified by modelling different alpine livestock system alternatives. Thirty-five Limousin heifers, initially weighing 383 +/- 45 kg, were fed fresh grass at 400 or 2000 m above sea level, or a 1:1 mixture of alpine grass and lowland grass hay at 2000 m. After 9 weeks, the six heaviest and oldest animals per group were slaughtered. The remaining animals were finished for 8 weeks on a silage-concentrate diet in the lowlands to similar age and body weight as the first slaughtered group. Carcass and meat quality (M. longissimus thoracis) were assessed in various respects. The average daily gains achieved were of about 600 g/d and similar between forage-type groups. Dressing percentage was 53.5% in the alpine and 57.2% in the lowland group. Carcass conformation and fat cover scores did not differ between forage-type groups. The meat from the alpine groups had greater ultimate pH and smaller redness, yellowness and protein contents. Still, these differences were of minor practical relevance. There was no forage-type effect on water-holding capacity and shear force of the meat. The alpine systems enhanced the proportion of alpha-linolenic acid in intramuscular fat and decreased the levels of some volatile compounds in perirenal fat. Finishing resulted in compensatory growth, especially in the animals previously fed lowland grass. There was a trend for the finished compared with the non finished groups towards greater carcass fat cover and intramuscular fat content. Additionally, ultimate pH was smaller and cooking loss was greater with than without finishing. Meat colour differences were also observed. Shear force was not affected by finishing. The finished animals had a smaller alpha-linolenic acid proportion in the intramuscular fat. In conclusion, the forage type had small effects on carcass and meat quality. Finishing did not substantially improve carcass and meat quality. The (alpine) grass-specific differences in fatty acid profile found in the unfinished cattle were not present in the finished animals. PMID- 26822887 TI - BRCA1-hapoinsufficiency: Unraveling the molecular and cellular basis for tissue specific cancer. AB - Over the past 20 years tremendous progress has been made in understanding the function of BRCA1 gene products. Yet one question still remains: why is mutation of BRCA1 typically associated with preferential development of breast and ovarian cancers and not tumors in other tissues? Here we discuss recent evidence documenting the effect of BRCA1-haploinsufficiency in different cells and tissues and synthesize a model for how mutations in a single BRCA1 allele in human cells might preferentially confer increased cancer risk in breast epithelial cells. PMID- 26822888 TI - Living at the edge of an interface area in Zimbabwe: cattle owners, commodity chain and health workers' awareness, perceptions and practices on zoonoses. AB - BACKGROUND: In the great Limpopo transfrontier conservation area (GLTFCA), there is an increased interface between wildlife and domestic animals, because rural households move their cattle into the game park in search of grazing and watering resources. This creates opportunities for inter-species transmission of infectious diseases, including zoonoses like brucellosis and tuberculosis, which may also pose a health risk to the local rural communities. This study investigated the awareness, perceptions and practices on zoonoses amongst rural cattle owners, commodity chain- and health-workers in three different localities around Gonarezhou National Park (GNP), Zimbabwe, where the interface between wild and domestic animals varies. METHODS: A cross-sectional study was conducted in Malipati, Chikombedzi and Chiredzi that are considered to be high-, medium- and low-domestic animal-wildlife interface areas, respectively. Data was collected from cattle owners, commodity chain and health-workers using a semi-structured questionnaire. To determine the public health risk of food-borne zoonoses, their practices with regard to meat and milk consumptions, and measures they take to prevent exposure to infections were assessed. Data were analyzed using descriptive statistics and principal component analysis. RESULTS: Most respondents (52.8 %, 102/193) were cattle owners, followed by health (30.1 %, 58/193) and lastly commodity chain workers (17.1 %, 33/193). Overall 67.4 % (130/193) of the respondents were aware of zoonoses with respective 48, 81.8, and 93.1 % of cattle owners, commodity chain, and health workers, being aware. Significantly more cattle owners (P < 0.05) from medium and low interface areas were aware of zoonoses compared to those from high interface areas. All categories of respondents cited anthrax (69.2 %), rabies (57.7 %), tuberculosis (41.5 %) and brucellosis (23.9 %) as important zoonoses. About half (46.1 %; 89/193) of the respondents perceive wildlife as important reservoirs of zoonoses. High proportions 98.4 % (190/193) and 96.4 % (186/193) of the respondents indicated that they consume meat and milk, respectively. Access to game meat and milk from informal markets was closely associated with consumption of raw meat and milk. CONCLUSIONS: Fewer cattle owners from a high interface area of Malipati are aware of zoonoses compared to other areas due to combined effects of limited education and other factors disadvantaging these marginalised areas. This may increase their risk of exposure to zoonoses, considering that consumption of raw meat and milk is common. Thus, awareness campaigns may reduce the public health impact of zoonoses at the interface. PMID- 26822889 TI - Systematic review of treatments for diabetic peripheral neuropathy. AB - AIM: To evaluate treatment options for neuropathic pain and sensory symptoms resulting from diabetic peripheral neuropathy of the feet. METHODS: The databases PubMed, Embase and Web-of-Science were searched for randomized controlled trials, published in the period from database inception to 2 July 2015, that evaluated treatments for diabetic peripheral neuropathy of the feet with placebo or standard treatment as comparators. Participants in these trials included people with diabetes mellitus and diabetic peripheral neuropathy who were given any treatment for diabetic peripheral neuropathy. Risk of bias was assessed using the Delphi list of criteria. Data from the trials were extracted using standardized data extraction sheets by two authors independently. All analyses were performed using RevMan 5.2. In case of clinical homogeneity, statistical pooling was performed using a random effects model. RESULTS: This review included 27 trials on pharmacological, non-pharmacological and alternative treatments. In the meta analysis of trials of alpha-lipoic acid versus placebo, total symptom score was reduced by -2.45 (95% CI -4.52; -0.39) with 600 mg i.v. alpha-lipoic acid (three trials), and was reduced by -1.95 (95% CI -2.89; -1.01) with 600 mg oral alpha lipoic acid (two trials). Significant improvements in diabetic peripheral neuropathy symptoms were found with opioids, botulinum toxin A, mexidol, reflexology and Thai foot massage, but not with micronutrients, neurotrophic peptide ORG 2677 and photon stimulation therapy. CONCLUSION: In this review, we found that alpha-lipoic acid, opioids, botulinum toxin A, mexidol, reflexology and Thai foot massage had significant beneficial results. PMID- 26822890 TI - Left atrial appendage morphology, echocardiographic characterization, procedural data and in-hospital outcome of patients receiving left atrial appendage occlusion device implantation: a prospective observational study. AB - BACKGROUND: Implantation of left atrial appendage (LAA) occlusion devices was shown to be a feasible and effective alternative to oral anticoagulation in patients with non-valvular atrial fibrillation. However, only few data about in hospital and peri-procedural data are currently available. This study aims to report about echocardiographic, procedural and in-hospital data of patients receiving LAA occlusion devices. METHODS: This single-center, prospective and observational study includes consecutively patients being eligible for percutaneous implantation of LAA occlusion devices (either WatchmanTM or AmplatzerTM Cardiac Plug 2). Data on pre- and peri-procedural transesophageal echocardiography (TEE), implantation and procedure related in-hospital complications were collected. The primary efficacy outcome measure was a successful device implantation without relevant peri-device leaks (i.e., < 5 mm). RESULTS: In total, 37 patients were included, 22 receiving the WatchmanTM and 15 ACP 2 device. Baseline characteristics did not differ significantly in both patient groups. The primary efficacy outcome measure was reached in 91.9% of patients (90.9% for the WatchmanTM, 93.3 % for the ACP 2 group). One device embolization (WatchmanTM group) with successful retrieval occurred (2.7% of patients). No thromboembolism or device thrombosis were present. The majority of bleedings was caused by access site bleedings (88.3% of all bleedings), consisting mostly of mild hematomas corresponding to a BARC type 1 bleeding (80.0% of all access-site complications). One patient died due to septic shock (non-procedure related). CONCLUSIONS: In daily real-life practice, percutaneous treatment with LAA occlusion devices appears to be an effective and safe. PMID- 26822892 TI - Childhood and Adolescent Thyroid Cancer in Fukushima after the Fukushima Daiichi Nuclear Power Plant Accident: 5 Years On. AB - The accident at the Fukushima Daiichi Nuclear Power Plant occurred after the Great East Japan Earthquake on 11 March 2011, releasing a large amount of radioactive materials into the atmosphere. Questions were raised regarding the health effects of radiation exposure, which led to increased anxiety among the Fukushima residents about the possible development of thyroid cancer. Thus, thyroid ultrasound examinations began for those who were from the areas where the radiation doses were highest, and will continue for the long term. In total, 300 476 subjects aged 18 years or younger at the time of the disaster were screened from 9 October 2011 to 31 March 2014. The participation rate was 81.7% of the total population of this age and in the affected area. Among them, the proportions of those who fell into the categories A1 (no nodules or cysts present), A2 (nodule <= 5 mm or cyst <= 20 mm diameter), B (nodule > 5 mm or cyst > 20 mm diameter) and C (immediate need for further investigation) were 51.5, 47.8, 0.8 and 0%, respectively; 2294 subjects in categories B and C were recommended to undergo a confirmatory examination; 113 were subsequently diagnosed with malignancy or suspected malignancy by fine needle aspiration cytology. The full-scale survey (second round survey) began in April 2014, and was completed by 30 June 2015, and comprised 169 455 subjects (participation rate; 44.7%). The proportions of those who fell into the categories A1, A2, B and C were 41.6, 57.6, 0.8 and 0% (no case), respectively; 1223 subjects in category B were recommended to undergo a confirmatory examination, 25 of these were subsequently diagnosed with malignancy or suspected malignancy by fine needle aspiration cytology. The thyroid cancers identified in this survey so far are unlikely to be due to radiation exposure, and are more likely to be the result of screening using highly sophisticated ultrasound techniques. However, it would be advisable to continue long-term screening to determine whether the risk of childhood and adolescent thyroid cancer due to radiation exposure increases or not. PMID- 26822891 TI - Beclin1 and HMGB1 ameliorate the alpha-synuclein-mediated autophagy inhibition in PC12 cells. AB - BACKGROUND: Aberrant alpha-synuclein aggregation due to the deficiency of ubiquitin-proteasome or of autophagy characterizes the parkinson disease (PD). High mobility group box 1 (HMGB1) is a novel stress sensor to mediate the persistent neuro-inflammation and the consequent progressive neurodegeneration, via controlling the cellular autophagy/apoptosis checkpoint during inflammation. Moreover, HMGB1 has been recently indicated to involve in the autophagic degradation of alpha-synuclein. METHODS: In the current study, we investigated the influence of the overexpressed alpha-synuclein of wild type (wt) or mutant type (A53T and A30P, mt) on the cytosolic levels of HMGB1 and Beclin1 and on the starvation-induced autophagy in pheochromocytoma PC12 cells. And then we explored the overexpression of HMGB1 or of Beclin1 on the alpha-synuclein degradation and on the autophagy in the alpha-synuclein-overexpressed PC12 cells. RESULTS: It was demonstrated that alpha-synuclein overexpression inhibited the trans-location of HMGB1 from nucleus to cytosol and reduced the cytosolic level of Beclin1 in PC12 cells, and inhibited the starvation-induced autophagy via downregulating autophagy-associated markers and via reducing the autophagic vesicles in PC12 cells under starvation. On the other side, the intracellular promotion of either HMGB1 or Beclin1 upregulated the alpha-synuclein degradation and ameliorated the alpha-synuclein-mediated autophagy reduction in PC12 cells. However, the exogenous HMGB1 treatment exerted no such regulation in PC12 cells. CONCLUSION: In summary, our study confirmed the positive regulation by HMGB1 and Beclin1 on the alpha-synuclein degradation and on the starvation-induced autophagy in PC12 cells, implying both markers as prominent targets to promote the alpha-synuclein degradation. PMID- 26822893 TI - Mussel-Directed Synthesis of Nitrogen-Doped Anatase TiO2. AB - Structure-forming processes leading to biominerals are well worth learning in pursuit of new synthetic techniques. Strategies that attempt to mimic nature in vitro cannot replace an entire complex natural organism, requiring ingenuity beyond chemists' hands. A "bioprocess-inspired synthesis" is demonstrated for fabrication of N-doped TiO2 materials at ambient temperature by direct implantation of precursor into living mussels. The amorphous precursor transforms into N-doped anatase TiO2 with a hierarchical nanostructure. Synthetic TiO2 exhibits high phase stability and enhanced visible-light photocatalytic activity as a result of modifications to its band gap during in vivo mineralization. Intracellular proteins were found to be involved in TiO2 mineralization. Our findings may inspire material production by new synthetic techniques, especially under environmentally benign conditions. PMID- 26822895 TI - Persistently high exhaled nitric oxide and loss of lung function in controlled asthma. AB - BACKGROUNDS: It remains unclear whether a persistently high exhaled nitric oxide fraction (FeNO) in patients with controlled asthma is associated with the progressive loss of lung function. METHODS: This was a 3-year prospective study. We examined the changes in pre- and post-bronchodilator forced expiratory volume in 1 s (FEV1) and FeNO in 140 patients with controlled asthma. We initially determined the FeNO cut-off point for identifying patients with a rapid decline in FEV1 (>40 mL/yr). Next, a total of 122 patients who maintained high or non high FeNO were selected, and the associations between the FeNO trend and changes in FEV1 and bronchodilator response (BDR) were investigated. RESULTS: A FeNO level >40.3 ppb yielded 43% sensitivity and 86% specificity for identifying patients with a rapid decline in FEV1. Patients with persistently high FeNO had higher rates of decline in FEV1 (42.7 +/- 37.5 mL/yr) than patients with non-high FeNO (16.7 +/- 31.5 mL/yr) (p < 0.0005). The changes in BDR from baseline to the end of the study, in patients who had high or non-high levels of FeNO were -0.8% and 0.1%, respectively (p < 0.01). In a multivariate analysis adjusted by age, body mass index, asthma control, blood eosinophil numbers, and FEV1% of predicted, a FeNO level of >=40 ppb was independently associated with an accelerated decline in FEV1 (p < 0.05). CONCLUSIONS: This study suggests that FeNO is potentially valuable tool for identifying individuals who are at risk of a progressive loss of lung function among patients with controlled asthma. PMID- 26822896 TI - Breast cancer treatment in mutation carriers: surgical treatment. AB - The surgical option which should be reserved for patients with BRCA1/2 mutation and breast cancer diagnosis is still debated. Several aspects should be considered before the surgical decision-making: the risk of ipsilateral breast recurrence (IBR), the risk of contralateral breast cancer (CBC), the potential survival benefit of prophylactic mastectomy, and the possible risk factors that could either increase or decrease the risk for IBR or CBC. Breast conservative treatment (BCT) does not increase the risk for IBR in BRCA mutation carriers compared to non-carriers in short term follow-up; however, an increased risk for IBR in carriers was observed in studies with long follow-up. In spite of the increased risk for IBR in patients who underwent BCT than patients with mastectomy, no significant difference in breast-cancer specific or overall survival was observed by local treatment type at 15 years. Patients with BRCA mutation had a higher risk for CBC compared with non-carriers and BRCA1-mutation carriers had an increased risk for CBC compared to BRCA2-mutation carriers. Bilateral mastectomy is intended to prevent CBC in BRCA mutation carriers, however, no difference in survival was found if a contralateral prophylactic mastectomy was performed or not. For higher-risk groups of BRCA mutated patients, a more-aggressive surgical approach may be preferable, but there are some aspects that should be considered in the surgical decision-making process. The use of adjuvant chemotherapy and performing oophorectomy are associated with a decreased risk for IBR. When considering the risk for CBC, three risk factors were associated with significantly decreased risk: the use of adjuvant tamoxifen, performing oophorectomy and older age at first breast cancer diagnosis. As a result, we could identify a group of patients that might benefit from a more aggressive surgical approach (unilateral mastectomy or unilateral therapeutic mastectomy with concomitant contralateral prophylactic mastectomy). For women with BRCA mutations candidate to mastectomy, preservation of the nipple-areola complex (NAC) may be highly important due to the generally younger age at time of surgery. Concerning the oncological safety, nipple sparing mastectomy (NSM) is an acceptable option, with no evidence of compromise to oncological safety at short term follow-up. The evaluation of surgical treatment in breast cancer patients with BRCA 1/2 mutation, should include several issues, namely the current evidence of adequate oncological safety of BCT in BRCA mutated patients; the increased risk for CBC especially in BRCA1 carriers; the feasibility on NSM with a greater patient's satisfaction for cosmetic results with no evidence of compromised oncological safety and, finally, the awareness that breast radiotherapy might increase the risk of complications in a possible subsequent mastectomy with immediate breast reconstruction. PMID- 26822894 TI - Fish connectivity mapping: linking chemical stressors by their mechanisms of action-driven transcriptomic profiles. AB - BACKGROUND: A very large and rapidly growing collection of transcriptomic profiles in public repositories is potentially of great value to developing data driven bioinformatics applications for toxicology/ecotoxicology. Modeled on human connectivity mapping (Cmap) in biomedical research, this study was undertaken to investigate the utility of an analogous Cmap approach in ecotoxicology. Over 3500 zebrafish (Danio rerio) and fathead minnow (Pimephales promelas) transcriptomic profiles, each associated with one of several dozen chemical treatment conditions, were compiled into three distinct collections of rank-ordered gene lists (ROGLs) by species and microarray platforms. Individual query signatures, each consisting of multiple gene probes differentially expressed in a chemical condition, were used to interrogate the reference ROGLs. RESULTS: Informative connections were established at high success rates within species when, as defined by their mechanisms of action (MOAs), both query signatures and ROGLs were associated with the same or similar chemicals. Thus, a simple query signature functioned effectively as an exposure biomarker without need for a time consuming process of development and validation. More importantly, a large reference database of ROGLs also enabled a query signature to cross-interrogate other chemical conditions with overlapping MOAs, leading to novel groupings and subgroupings of seemingly unrelated chemicals at a finer resolution. This approach confirmed the identities of several estrogenic chemicals, as well as a polycyclic aromatic hydrocarbon and a neuro-toxin, in the largely uncharacterized water samples near several waste water treatment plants, and thus demonstrates its future potential utility in real world applications. CONCLUSIONS: The power of Cmap should grow as chemical coverages of ROGLs increase, making it a framework easily scalable in the future. The feasibility of toxicity extrapolation across fish species using Cmap needs more study, however, as more gene expression profiles linked to chemical conditions common to multiple fish species are needed. PMID- 26822897 TI - Successful immune tolerance induction with von Willebrand factor containing concentrate in an adult with haemophilia A and chronic inhibitor - a case study. PMID- 26822898 TI - Electronic cigarettes: the renormalisation of nicotine use. PMID- 26822899 TI - Chesapeake Bay fish-osprey (Pandion haliaetus) food chain: Evaluation of contaminant exposure and genetic damage. AB - From 2011 to 2013, a large-scale ecotoxicological study was conducted in several Chesapeake Bay (USA) tributaries (Susquehanna River and flats, the Back, Baltimore Harbor/Patapsco Rivers, Anacostia/ middle Potomac, Elizabeth and James Rivers) and Poplar Island as a mid-Bay reference site. Osprey (Pandion haliaetus) diet and the transfer of contaminants from fish to osprey eggs were evaluated. The most bioaccumulative compounds (biomagnification factor > 5) included p,p' dichlorodiphenyldichloroethylene (DDE), total polychlorinated biphenyls (PCBs), total polybrominated diphenyl ethers (PBDEs), and bromodiphenyl ether (BDE) congeners 47, 99, 100, and 154. This analysis suggested that alternative brominated flame retardants and other compounds (methoxytriclosan) are not appreciably biomagnifying. A multivariate analysis of similarity indicated that major differences in patterns among study sites were driven by PCB congeners 105, 128, 156, 170/190, and 189, and PBDE congeners 99 and 209. An integrative redundancy analysis showed that osprey eggs from Baltimore Harbor/Patapsco River and the Elizabeth River had high residues of PCBs and p,p'-DDE, with PBDEs making a substantial contribution to overall halogenated contamination on the Susquehanna and Anacostia/middle Potomac Rivers. The redundancy analysis also suggested a potential relation between PBDE residues in osprey eggs and oxidative DNA damage in nestling blood samples. The results also indicate that there is no longer a discernible relation between halogenated contaminants in osprey eggs and their reproductive success in Chesapeake Bay. Osprey populations are thriving in much of the Chesapeake, with productivity rates exceeding those required to sustain a stable population. Environ Toxicol Chem 2016;35:1560-1575. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America. PMID- 26822900 TI - Site-selective local fluorination of graphene induced by focused ion beam irradiation. AB - The functionalization of graphene remains an important challenge for numerous applications expected by this fascinating material. To keep advantageous properties of graphene after modification or functionalization of its structure, local approaches are a promising road. A novel technique is reported here that allows precise site-selective fluorination of graphene. The basic idea of this approach consists in the local radicalization of graphene by focused ion beam (FIB) irradiation and simultaneous introduction of XeF2 gas. A systematic series of experiments were carried out to outline the relation between inserted defect creation and the fluorination process. Based on a subsequent X-ray photoelectron spectroscopy (XPS) analysis, a 6-fold increase of the fluorine concentration on graphene under simultaneous irradiation was observed when compared to fluorination under normal conditions. The fluorine atoms are predominately localized at the defects as indicated from scanning tunneling microscopy (STM). The experimental findings are confirmed by density functional theory which predicts a strong increase of the binding energy of fluorine atoms when bound to the defect sites. The developed technique allows for local fluorination of graphene without using resists and has potential to be a general enabler of site selective functionalization of graphene using a wide range of gases. PMID- 26822901 TI - High susceptibility prevalence for F4+ and F18+Escherichia coli in Flemish pigs. AB - F4 and/or F18 enterotoxigenic Escherichia coli (F4+/F18+ ETEC) are responsible for diarrhea while F18+ verotoxigenic E. coli (F18+ VTEC) cause edema disease in pigs. Both infections can result in severe economic losses, which are mainly the result of the medication, growth retardation and mortality. The susceptibility of piglets to these pathogens is determined by the presence of F4 and F18 receptors (F4R and F18R). Understanding the composition of the susceptibility phenotypes of pigs is useful for animal health and breeding management. This study aimed to determine the prevalence of the F4 ETEC susceptibility phenotypes and F18+E. coli susceptibility among Flemish pig breeds by using the in vitro villous adhesion assay. In this study, seven F4 ETEC susceptibility phenotypes were found, namely A (F4abR+,acR+,adR+; 59.16%), B (F4abR+,acR+,adR-; 6.28%), C (F4abR+,acR-,adR+; 2.62%), D (F4abR-,acR-,adR+; 6.28%), E (F4abR-,acR-,adR-; 24.08%), F (F4abR+,acR ,adR-; 1.05%) and G (F4abR-,acR+,adR-; 0.52%). F4ab and F4ac E. coli showed a stronger degree of adhesion to the intestinal villi (53.40% and 52.88% strong adhesion, respectively), compared to F4ad E. coli (43.46% strong adhesion). Furthermore, the correlation between F4ac and F4ab adhesion was higher (r=0.78) than between F4ac and F4ad adhesion (r=0.41) and between F4ab and F4ad adhesion (r=0.57). For F18+E. coli susceptibility, seven out of 82 pigs were F18R negative (8.54%), but only two of these seven pigs (2.44%) were also negative for F4R. As such, the chance to identify a pig that is positive for a F4 ETEC variant or F18+E. coli is 97.56%. Therefore, significant economic losses will arise due to F4+ and/or F18+E. coli infections in the Flemish pig population due to the high susceptibility prevalence. PMID- 26822902 TI - Tracheostomy Placement in Children Younger Than 2 Years: 30-Day Outcomes Using the National Surgical Quality Improvement Program Pediatric. AB - IMPORTANCE: Analysis of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) Pediatric demonstrated that the highest contribution to composite morbidity in otolaryngology is seen in children younger than 2 years undergoing tracheostomy. OBJECTIVE: To determine predictive factors for complications following tracheostomy placement in patients younger than 2 years that, if targeted for reduction in quality initiatives, might result in improved surgical outcomes. DESIGN, SETTING, AND PARTICIPANTS: The NSQIP Pediatric reports predefined 30-day postoperative outcomes for surgical cases from participating institutions for quality improvement. All 206 cases of elective tracheostomy performed in children younger than 2 years from 2012 to 2013 among 61 participating institutions and documented in the NSQIP Pediatric public use file were included. Data analysis was conducted from December 1, 2014, to June 30, 2015. INTERVENTIONS: Surgical placement of tracheostomy in children younger than 2 years. MAIN OUTCOMES AND MEASURES: Demographics and clinical and perioperative characteristics for children who did and did not experience a major complication from elective tracheostomy were compared. Continuous variables were compared using Wilcoxon rank sum tests and categorical variables were compared using Pearson chi2 tests or Fisher exact tests where appropriate. A logistic regression model was fit to identify adjusted odds ratios (aORs) with 95% CIs of preoperative factors predictive of occurrence of a major complication. RESULTS: Of the 206 children younger than 2 years who underwent tracheostomy, 50 (24.3%) experienced a major complication within 30 days. The most common complications were pneumonia (16 [7.8%]), postoperative sepsis (12 [5.8%]), death (12 [5.8%]), and deep or organ space surgical site infections (8 [3.9%]). Neonatal age (aOR, 2.38; 95% CI, 1.06-5.37; P = .04), intraventricular hemorrhage (aOR, 2.72; 95% CI, 1.01-7.32; P = .048), and comorbid cardiac risk factors (relative to none: minor risk factors, aOR, 2.94; 95% CI, 1.19-7.24; major or severe risk factors, aOR, 1.31; 95% CI, 0.44-3.84; P = .04 for all cardiac risk factors) were independently predictive of major complications. CONCLUSIONS AND RELEVANCE: Young children undergoing tracheostomy tube placement have high rates of morbidity. This analysis identifies the need for additional procedure-specific outcome variables and improved variable definitions to incorporate into a detailed module for NSQIP Pediatric that will more effectively promote national, specialty specific targeted quality improvement efforts. PMID- 26822903 TI - Insecticidal potency of RNAi-based catalase knockdown in Rhynchophorus ferrugineus (Oliver) (Coleoptera: Curculionidae). AB - BACKGROUND: Palm trees around the world are prone to notorious Rhynchophorus ferrugineus, which causes heavy losses of palm plantations. In Middle Eastern countries, this pest is a major threat to date palm orchards. Conventional pest control measures with the major share of synthetic insecticides have resulted in insect resistance and environmental issues. Therefore, in order to explore better alternatives, the RNAi approach was employed to knock down the catalase gene in fifth and tenth larval instars with different dsRNA application methods, and their insecticidal potency was studied. RESULTS: dsRNA of 444 bp was prepared to knock down catalase in R. ferrugineus. Out of the three dsRNA application methods, dsRNA injection into larvae was the most effective, followed by dsRNA application by artificial feeding. Both methods resulted in significant catalase knockdown in various tissues, especially the midgut. As a result, the highest growth inhibition of 123.49 and 103.47% and larval mortality of 80 and 40% were observed in fifth-instar larvae, whereas larval growth inhibition remained at 86.83 and 69.08% with larval mortality at 30 and 10% in tenth-instar larvae after dsRNA injection and artificial diet treatment. The topical application method was the least efficient, with the lowest larval growth inhibition of 57.23 and 45.61% and 0% mortality in fifth- and tenth-instar larvae. Generally, better results were noted at the high dsRNA dose of 5 uL. CONCLUSION: Catalase enzyme is found in most insect body tissues, and thus its dsRNA can cause broad-scale gene knockdown within the insect body, depending upon the application method. Significant larval mortality and growth inhibition after catalase knockdown in R. ferrugineus confirms its insecticidal potency and suggests a bright future for RNAi-based bioinsecticides in pest control. (c) 2016 Society of Chemical Industry. PMID- 26822904 TI - [Crizotinib: At last in first-line treatment of advanced-stage ALK-rearranged non small cell lung cancer]. PMID- 26822905 TI - [Stage IB2, IIA and IIB cervical carcinoma without lymph node extension treated with neoadjuvant chemoradiotherapy]. AB - PURPOSE: To evaluate the results of preoperative chemoradiation for resectable bulky cervical carcinoma without lymph node involvement after surgical lymph node staging. PATIENTS AND METHODS: Between 2000 and 2010, 45 patients with cervical carcinoma stage IB2 (11 patients), IIA2 (3 patients) and IIB with proximal parametrial invasion (31 patients) were treated with pelvic radiation therapy at a dose of 40.5Gy and concurrent platin (44 patients) or mitomycin (one patient). Forty-two patients had low-dose-rate preoperative uterovaginal brachytherapy at a dose of 20Gy. All patients underwent hysterectomy. Three patients had postoperative low-dose-rate vaginal brachytherapy at a dose of 20Gy. The median follow-up was 34 months. RESULTS: A pathologic cervical residual tumor was observed in 16 patients (35.6%). Six patients presented a relapse (13.3%) with a median delay of 8 months. The 5-year overall survival and disease free survival rates were 88.4% and 84.7%, respectively. In univariable analysis, a cervical residual tumor was the only predictive factor of overall survival (P=0.03). Late toxicity was observed in seven patients. CONCLUSION: Chemoradiation followed by surgery for resectable bulky stage I-II cervical carcinoma without lymph node involvement on pretreatment surgical staging can be used with a good local control and a high rate of 5-year overall survival. PMID- 26822906 TI - [Ibrutinib prescription in B-cell lymphoid neoplasms]. AB - Ibrutinib is a new-targeted therapy that irreversibly and specifically inhibits the Bruton's Tyrosine Kinase (BTK), a key component of the signaling pathways of B cells. The results are very encouraging as monotherapy in the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Following the results of recent studies, ibrutinib is now available in France for these three diseases. PMID- 26822907 TI - Determination of Atto- to Femtogram Levels of Americium and Curium Isotopes in Large-Volume Urine Samples by Compact Accelerator Mass Spectrometry. AB - Ultralow level analysis of actinides in urine samples may be required for dose assessment in the event of internal exposures to these radionuclides at nuclear facilities and nuclear power plants. A new bioassay method for analysis of sub femtogram levels of Am and Cm in large-volume urine samples was developed. Americium and curium were co-precipitated with hydrous titanium oxide from the urine matrix and purified by column chromatography separation. After target preparation using mixed titanium/iron oxides, the final sample was measured by compact accelerator mass spectrometry. Urine samples spiked with known quantities of Am and Cm isotopes in the range of attogram to femtogram levels were measured for method evaluation. The results are in good agreement with the expected values, demonstrating the feasibility of compact accelerator mass spectrometry (AMS) for the determination of minor actinides at the levels of attogram/liter in urine samples to meet stringent sensitivity requirements for internal dosimetry assessment. PMID- 26822908 TI - Decline in abundance and health state of an Atlantic subtropical gorgonian population. AB - Losses in coral cover have been widely reported for the Caribbean. In contrast, much less is known about the health state of the Brazilian reef fauna, which was declared as a priority for Atlantic biodiversity conservation due to its high degree of endemism. In the present study, we assessed the general health state of Phyllogorgia dilatata assemblages at the subtropical reefs of Arraial do Cabo (southeastern Brazil), where observations suggest that the abundance of this endemic gorgonian species has declined. We found that about 49% of the sampled colonies were dead, and 73% of the living colonies were affected by tissue loss. Tissue loss initially manifested as multifocal holes in the planar colonial coenenchyme and peripheral tissue retraction leaving denuded skeletal axes. In combination with other recent studies, our results raise the awareness for an increasingly threatened Southwestern Atlantic reef coral fauna. PMID- 26822909 TI - Assessing genotoxic effects in fish from a marine protected area influenced by former mining activities and other stressors. AB - The goal of the current study was to evaluate different genotoxicity tools in order to assess a marine protected area (MPA) affected by former mining activities and urban settlements. A catfish (Cathorops spixii) was analyzed for genotoxic effects at the (i) molecular and at the (ii) chromosomal levels. Through factor analysis, genotoxicity was found to be linked to levels of metals bioaccumulated and PAH metabolites in the bile. Micronucleus and nuclear alteration were less vulnerable to the effects of confounding factors in mildly contaminated areas since they were more frequently associated with bioaccumulated metals than the DNA analysis. The different genotoxicity responses allowed for the identification of sources of pollution in the MPA. This approach was important for detecting environmental risks related to genotoxic contaminants in a mildly contaminated MPA. PMID- 26822910 TI - Enhanced product selectivity promoted by remote metal coordination in acceptor free alcohol dehydrogenation catalysis. AB - A bimetallic [Ir(3+)]2 complex was synthesized based on a bridging 1,2,3-triazole ligand that coordinates to one Cp*Ir unit as N,N-bidentate chelate, and to the other as a C,C-bidentate ligand. When compared to monometallic homologues, the bimetallic complex shows greatly enhanced product selectivity for the acceptorless dehydrogenation of alcohols; spectroscopic and electrochemical analysis suggest significant alteration of the metal properties in the bimetallic system compared to the monometallic species, which offers a rationale for the observed high selectivity. PMID- 26822911 TI - Evaluation of O2PLS in Omics data integration. AB - BACKGROUND: Rapid computational and technological developments made large amounts of omics data available in different biological levels. It is becoming clear that simultaneous data analysis methods are needed for better interpretation and understanding of the underlying systems biology. Different methods have been proposed for this task, among them Partial Least Squares (PLS) related methods. To also deal with orthogonal variation, systematic variation in the data unrelated to one another, we consider the Two-way Orthogonal PLS (O2PLS): an integrative data analysis method which is capable of modeling systematic variation, while providing more parsimonious models aiding interpretation. RESULTS: A simulation study to assess the performance of O2PLS showed positive results in both low and higher dimensions. More noise (50 % of the data) only affected the systematic part estimates. A data analysis was conducted using data on metabolomics and transcriptomics from a large Finnish cohort (DILGOM). A previous sequential study, using the same data, showed significant correlations between the Lipo-Leukocyte (LL) module and lipoprotein metabolites. The O2PLS results were in agreement with these findings, identifying almost the same set of co-varying variables. Moreover, our integrative approach identified other associative genes and metabolites, while taking into account systematic variation in the data. Including orthogonal components enhanced overall fit, but the orthogonal variation was difficult to interpret. CONCLUSIONS: Simulations showed that the O2PLS estimates were close to the true parameters in both low and higher dimensions. In the presence of more noise (50 %), the orthogonal part estimates could not distinguish well between joint and unique variation. The joint estimates were not systematically affected. Simultaneous analysis with O2PLS on metabolome and transcriptome data showed that the LL module, together with VLDL and HDL metabolites, were important for the metabolomic and transcriptomic relation. This is in agreement with an earlier study. In addition more gene expression and metabolites are identified being important for the joint covariation. PMID- 26822912 TI - Localized topical steroid use and central serous retinopathy. AB - OBJECTIVES: The link between topical steroid use and central serous retinopathy (CSR) is poorly understood as there are a limited number of reported cases, with most cases typically occurring in patients using oral or inhaled steroids. CSR is a common retinal disease that can cause loss of vision as a result of accumulated subretinal fluid leading to localized serous retinal detachments. CSR is associated with systemic steroid use. The objective of this case series and the review was to further understand the relationship between localized topical steroid use and CSR. METHODS: The medical charts of two patients who developed CSR after using topical steroids were reviewed. RESULTS: These cases demonstrate that CSR is associated with consistent topical steroid use to even limited areas of the body. These cases are unique, as other published cases describe patients who used topical steroids either on multiple or larger areas of the body. CONCLUSION: It is critical that dermatologists are aware of this association, and refer patients who develop ocular symptoms after using topical steroids to ophthalmology. PMID- 26822913 TI - Rapid gut growth but persistent delay in digestive function in the postnatal period of preterm pigs. AB - Preterm infants often tolerate full enteral nutrition a few weeks after birth but it is not known how this is related to gut maturation. Using pigs as models, we hypothesized that intestinal structure and digestive function are similar in preterm and term individuals at 3-4 wk after birth and that early enteral nutrition promotes maturation. Preterm or term cesarean-delivered pigs were fed total parenteral nutrition, or partial enteral nutrition [Enteral (Ent), 16-64 ml.kg(-1).day(-1) of bovine colostrum] for 5 days, followed by full enteral milk feeding until day 26 The intestine was collected for histological and biochemical analyses at days 0, 5, and 26 (n = 8-12 in each of 10 treatment groups). Intestinal weight (relative to body weight) was reduced in preterm pigs at 0-5 days but ENT feeding stimulated the mucosal volume and peptidase activities. Relative to term pigs, mucosal volume remained reduced in preterm pigs until 26 days although plasma glucagon-like peptide 2 (GLP-2) and glucose-dependent insulin-trophic peptide (GIP) levels were increased. Preterm pigs also showed reduced hexose absorptive capacity and brush-border enzyme (sucrase, maltase) activities at 26 days, relative to term pigs. Intestinal structure shows a remarkable growth adaptation in the first week after preterm birth, especially with enteral nutrition, whereas some digestive functions remain immature until at least 3-4 wk. It is important to identify feeding regimens that stimulate intestinal maturation in the postnatal period of preterm infants because some intestinal functions may show long-term developmental delay. PMID- 26822914 TI - Rapid disruption of intestinal epithelial tight junction and barrier dysfunction by ionizing radiation in mouse colon in vivo: protection by N-acetyl-l-cysteine. AB - The goals of this study were to evaluate the effects of ionizing radiation on apical junctions in colonic epithelium and mucosal barrier function in mice in vivo. Adult mice were subjected to total body irradiation (4 Gy) with or without N-acetyl-l-cysteine (NAC) feeding for 5 days before irradiation. At 2-24 h postirradiation, the integrity of colonic epithelial tight junctions (TJ), adherens junctions (AJ), and the actin cytoskeleton was assessed by immunofluorescence microscopy and immunoblot analysis of detergent-insoluble fractions for TJ and AJ proteins. The barrier function was evaluated by measuring vascular-to-luminal flux of fluorescein isothiocyanate (FITC)-inulin in vivo and luminal-to-mucosal flux in vitro. Oxidative stress was evaluated by measuring protein thiol oxidation. Confocal microscopy showed that radiation caused redistribution of occludin, zona occludens-1, claudin-3, E-cadherin, and beta catenin, as well as the actin cytoskeleton as early as 2 h postirradiation, and this effect was sustained for at least 24 h. Feeding NAC before irradiation blocked radiation-induced disruption of TJ, AJ, and the actin cytoskeleton. Radiation increased mucosal permeability to inulin in colon, which was blocked by NAC feeding. The level of reduced-protein thiols in colon was depleted by radiation with a concomitant increase in the level of oxidized-protein thiol. NAC feeding blocked the radiation-induced protein thiol oxidation. These data demonstrate that radiation rapidly disrupts TJ, AJ, and the actin cytoskeleton by an oxidative stress-dependent mechanism that can be prevented by NAC feeding. PMID- 26822915 TI - Pathogenic cellular role of the p.L104P human cationic trypsinogen variant in chronic pancreatitis. AB - Mutations in the PRSS1 gene encoding human cationic trypsinogen are associated with hereditary and sporadic chronic pancreatitis. High-penetrance PRSS1 mutations found in hereditary pancreatitis alter activation and/or degradation of cationic trypsinogen, thereby promoting intrapancreatic trypsinogen activation. In contrast, a number of rare PRSS1 variants identified in subjects with sporadic chronic pancreatitis cause misfolding and endoplasmic reticulum (ER) stress. Mutation p.L104P is unique among natural PRSS1 variants, since it affects the substrate binding site of trypsin. The aim of the present study was to establish the clinical significance of variant p.L104P through functional analysis. We found that p.L104P trypsin exhibited decreased activity on peptide and protein substrates; however, autoactivation was slightly accelerated. Remarkably, binding of the physiological trypsin inhibitor serine protease inhibitor Kazal type 1 (SPINK1) was decreased by 70-fold. In the presence of the trypsinogen-degrading enzyme chymotrypsin C, mutant p.L104P autoactivated to higher trypsin levels than wild-type trypsinogen. This apparent resistance to degradation was due to slower cleavage at Arg(122) rather than Leu(81) Finally, secretion of mutant p.L104P from transfected cells was markedly reduced due to intracellular retention and aggregation with concomitant elevation of ER stress markers. We conclude that PRSS1 variant p.L104P exhibits a variety of phenotypic changes that can increase risk for chronic pancreatitis. Mutation-induced misfolding and associated ER stress are the dominant effects that support a direct pathogenic role in chronic pancreatitis. PMID- 26822917 TI - Identification of different functional types of spinal afferent neurons innervating the mouse large intestine using a novel CGRPalpha transgenic reporter mouse. AB - Spinal afferent neurons detect noxious and physiological stimuli in visceral organs. Five functional classes of afferent terminals have been extensively characterized in the colorectum, primarily from axonal recordings. Little is known about the corresponding somata of these classes of afferents, including their morphology, neurochemistry, and electrophysiology. To address this, we made intracellular recordings from somata in L6/S1 dorsal root ganglia and applied intraluminal colonic distensions. A transgenic calcitonin gene-related peptide alpha (CGRPalpha)-mCherry reporter mouse, which enabled rapid identification of soma neurochemistry and morphology following electrophysiological recordings, was developed. Three distinct classes of low-threshold distension-sensitive colorectal afferent neurons were characterized; an additional group was distension-insensitive. Two of three low-threshold classes expressed CGRPalpha. One class expressing CGRPalpha discharged phasically, with inflections on the rising phase of their action potentials, at low frequencies, to both physiological (<30 mmHg) and noxious (>30 mmHg) distensions. The second class expressed CGRPalpha and discharged tonically, with smooth, briefer action potentials and significantly greater distension sensitivity than phasically firing neurons. A third class that lacked CGRPalpha generated the highest frequency firing to distension and had smaller somata. Thus, CGRPalpha expression in colorectal afferents was associated with lower distension sensitivity and firing rates and larger somata, while colorectal afferents that generated the highest firing frequencies to distension had the smallest somata and lacked CGRPalpha. These data fill significant gaps in our understanding of the different classes of colorectal afferent somata that give rise to distinct functional classes of colorectal afferents. In healthy mice, the majority of sensory neurons that respond to colorectal distension are low-threshold, wide-dynamic-range afferents, encoding both physiological and noxious ranges. PMID- 26822916 TI - Role of microRNAs in gastrointestinal smooth muscle fibrosis and dysfunction: novel molecular perspectives on the pathophysiology and therapeutic targeting. AB - MicroRNAs (miRNAs) belong to a group of short noncoding RNA molecules with important roles in cellular biology. miRNAs regulate gene expression by repressing translation or degrading the target mRNA. Recently, a growing body of evidence suggests that miRNAs are implicated in many diseases and could be potential biomarkers. Fibrosis and/smooth muscle (SM) dysfunction contributes to the morbidity and mortality associated with several diseases of the gastrointestinal tract (GIT). Currently available therapeutic modalities are unsuccessful in efficiently blocking or reversing fibrosis and/or SM dysfunction. Recent understanding of the role of miRNAs in signaling pathway of fibrogenesis and SM phenotype switch has provided a new insight into translational research. However, much is still unknown about the molecular targets and therapeutic potential of miRNAs in the GIT. This review discusses miRNA biology, pathophysiology of fibrosis, and aging- associated SM dysfunction in relation to the deregulation of miRNAs in the GIT. We also highlight the role of selected miRNAs associated with fibrosis and SM dysfunction-related diseases of the GIT. PMID- 26822919 TI - Weight-based bullying and compromised peer relationships in young adult bariatric patients. AB - The experience of weight-based bullying in young adult bariatric patients has not yet been examined. Thirteen young adults (age, 18-24) that were seeking or had undergone bariatric surgery participated in semi-structured in-depth interviews. A thematic analysis informed by grounded theory principles was conducted. Analysis revealed the following three major themes: (1) being the biggest kid, (2) coping through avoidance, and (3) compromised peer and intimate relationships. Victims of weight-based bullying often avoid and withdraw socially in response to persistent verbal abuse. The decision to pursue bariatric surgery at a relatively young age adds another dimension of difficulty when navigating peer relationships. PMID- 26822918 TI - Implant success and safety of left atrial appendage closure with the WATCHMAN device: peri-procedural outcomes from the EWOLUTION registry. AB - AIMS: Left atrial appendage closure is a non-pharmacological alternative for stroke prevention in high-risk patients with non-valvular atrial fibrillation. The objective of the multicentre EWOLUTION registry was to obtain clinical data on procedural success and complications, and long-term patient outcomes, including bleeding and incidence of stroke/transient ischaemic attack (TIA). Here, we report on the peri-procedural outcomes of up to 30 days. METHODS AND RESULTS: Baseline/implant data are available for 1021 subjects. Subjects in the study were at high risk of stroke (average CHADS2 score: 2.8 +/- 1.3, CHA2DS2 VASc: 4.5 +/- 1.6) and moderate-to-high risk of bleeding (average HAS-BLED score: 2.3 +/- 1.2). Almost half of the subjects (45.4%) had a history of TIA, ischaemic stroke, or haemorrhagic stroke; 62% of patients were deemed unsuitable for novel oral anticoagulant by their physician. The device was successfully deployed in 98.5% of patients with no flow or minimal residual flow achieved in 99.3% of implanted patients. Twenty-eight subjects experienced 31 serious adverse events (SAEs) within 1 day of the procedure. The overall 30-day mortality rate was 0.7%. The most common SAE occurring within 30 days of the procedure was major bleeding requiring transfusion. Incidence of SAEs within 30 days was significantly lower for subjects deemed to be ineligible for oral anticoagulation therapy (OAT) compared with those eligible for OAT (6.5 vs. 10.2%, P = 0.042). CONCLUSION: Left atrial appendage closure with the WATCHMAN device has a high success rate in complete LAAC with low peri-procedural risk, even in a population with a higher risk of stroke and bleeding, and multiple co-morbidities. Improvement in implantation techniques has led to a reduction of peri-procedural complications previously limiting the net clinical benefit of the procedure. PMID- 26822923 TI - Diabetes: Increased potato consumption linked to GDM. PMID- 26822920 TI - Naturally occurring proteinaceous nanoparticles in Coptidis Rhizoma extract act as concentration-dependent carriers that facilitate berberine absorption. AB - Pharmacological activities of some natural products diminish and even disappear after purification. In this study, we explored the mechanisms underlying the decrease of acute oral toxicity of Coptidis Rhizoma extract after purification. The water solubility, in vitro absorption, and plasma exposure of berberine (the major active compound) in the Coptidis Rhizoma extract were much better than those of pure berberine. Scanning electron microscopy, laser scanning confocal microscopy (LSCM), and dynamic light scattering experiments confirmed that nanoparticles attached to very fine precipitates existed in the aqueous extract solution. The LSCM experiment showed that the precipitates were absorbed with the particles by the mouse intestine. High-speed centrifugation of the extract could not remove the nanoparticles and did not influence plasma exposure or acute oral toxicity. However, after extract dilution, the attached precipitates vanished, although the nanoparticles were preserved, and there were no differences in the acute oral toxicity and plasma exposure between the extract and pure berberine. The nanoparticles were then purified and identified as proteinaceous. Furthermore, they could absorb co-dissolved berberine. Our results indicate that naturally occurring proteinaceous nanoparticles in Coptidis Rhizoma extract act as concentration-dependent carriers that facilitate berberine absorption. These findings should inspire related studies in other natural products. PMID- 26822924 TI - Neuroendocrinology: FGF21 influences a 'sweet tooth' in mice. PMID- 26822925 TI - Thyroid cancer: Use of MDSC to assess malignancy. PMID- 26822926 TI - PCOS in 2015: New insights into the genetics of polycystic ovary syndrome. PMID- 26822928 TI - Obesity: How dangerous is weight gain between pregnancies? PMID- 26822929 TI - Viable Cesarean scar pregnancy managed by sonographically guided application of a fibrin sealant. PMID- 26822930 TI - Identification of Enzyme Genes Using Chemical Structure Alignments of Substrate Product Pairs. AB - Although there are several databases that contain data on many metabolites and reactions in biochemical pathways, there is still a big gap in the numbers between experimentally identified enzymes and metabolites. It is supposed that many catalytic enzyme genes are still unknown. Although there are previous studies that estimate the number of candidate enzyme genes, these studies required some additional information aside from the structures of metabolites such as gene expression and order in the genome. In this study, we developed a novel method to identify a candidate enzyme gene of a reaction using the chemical structures of the substrate-product pair (reactant pair). The proposed method is based on a search for similar reactant pairs in a reference database and offers ortholog groups that possibly mediate the given reaction. We applied the proposed method to two experimentally validated reactions. As a result, we confirmed that the histidine transaminase was correctly identified. Although our method could not directly identify the asparagine oxo-acid transaminase, we successfully found the paralog gene most similar to the correct enzyme gene. We also applied our method to infer candidate enzyme genes in the mesaconate pathway. The advantage of our method lies in the prediction of possible genes for orphan enzyme reactions where any associated gene sequences are not determined yet. We believe that this approach will facilitate experimental identification of genes for orphan enzymes. PMID- 26822931 TI - The consumption of two or more fall risk-increasing drugs rather than polypharmacy is associated with falls. AB - AIM: The presemt study aimed to determine the association between the risk of recurrent and injurious falls with polypharmacy, fall risk-increasing drugs (FRID) and FRID count among community-dwelling older adults. METHODS: Participants (n = 202) were aged >=65 years with two or more falls or one injurious fall in the past year, whereas controls (n = 156) included volunteers aged >=65 years with no falls in the past year. A detailed medication history was obtained alongside demographic data. Polypharmacy was defined as "regular use of five or more prescription drugs." FRID were identified as cardiovascular agents, central nervous system drugs, analgesics and endocrine drugs; multiple FRID were defined as two or more FRID. Multiple logistic regression analyses were used to adjust for confounders. RESULTS: The use of non-steroidal anti-inflammatory drugs was independently associated with an increased risk of falls. Univariate analyses showed both polypharmacy (OR 2.23, 95% CI 1.39-3.56; P = 0.001) and the use of two or more FRID (OR 2.9, 95% CI 1.9-4.5; P = 0.0001) were significantly more likely amongst fallers. After adjustment for age, sex and comorbidities, blood pressure, and physical performance scores, polypharmacy was no longer associated with falls (OR 1.6, 95% CI 0.9-2.9; P = 0.102), whereas the consumption of two or more FRID remained a significant predictor for falls (OR 2.8, 95% CI 1.4-5.3; P = 0.001). CONCLUSIONS: Among high risk fallers, the use of two or more FRID was an independent risk factor for falls instead of polypharmacy. Our findings will inform clinical practice in terms of medication reviews among older adults at higher risk of falls. Future intervention studies will seek to confirm whether avoidance or withdrawal of multiple FRID reduces the risk of future falls. Geriatr Gerontol Int 2017; 17: 463-470. PMID- 26822932 TI - Hepatitis B prevalence and treatment needs among Tibetan refugees residing in India. AB - Untreated chronic hepatitis B can lead to liver failure and/or liver cancer. These complications can be avoided through prevention with vaccination or treatment of disease. To inform health policy for the Tibetan community in India, we conducted study of hepatitis B prevalence and treatment needs. We conducted a cross-sectional study over 3 months of 2013. Households were randomly selected for participation via a satellite map; one boarding school and one residential monastery were also included. Participants were asked questions and a whole blood sample was collected for HBsAg assay. Participants with a positive HBsAg result were tested for hepatitis B e antigen, ALT, and AST. Participants with a negative HBsAg result were tested for anti-hepatitis B core antibodies. We recruited 2,769 participants; of which 247 (8.9%) were positive for HBsAg. Participants more likely to have a positive HBsAg result were those born in Tibet (12.4%) and aged 30-59 years old. Of those with a positive HBsAg result, 60.7% were positive for hepatitis B e antigen 7% of whom fit into a likely treatment-needed category; the others fit into management categories requiring repeat ALT testing with or without liver fibrosis assessment. Among participants negative for HBsAg, 52.9% from household sampling had anti-HBc antibodies. We identified a high endemicity of chronic hepatitis B in a Tibetan community in India. Resource appropriate approaches are needed for managing chronic hepatitis B in settings such as this one. J. Med. Virol. 88:1357-1363, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26822933 TI - E. coli metabolic protein aldehyde-alcohol dehydrogenase-E binds to the ribosome: a unique moonlighting action revealed. AB - It is becoming increasingly evident that a high degree of regulation is involved in the protein synthesis machinery entailing more interacting regulatory factors. A multitude of proteins have been identified recently which show regulatory function upon binding to the ribosome. Here, we identify tight association of a metabolic protein aldehyde-alcohol dehydrogenase E (AdhE) with the E. coli 70S ribosome isolated from cell extract under low salt wash conditions. Cryo-EM reconstruction of the ribosome sample allows us to localize its position on the head of the small subunit, near the mRNA entrance. Our study demonstrates substantial RNA unwinding activity of AdhE which can account for the ability of ribosome to translate through downstream of at least certain mRNA helices. Thus far, in E. coli, no ribosome-associated factor has been identified that shows downstream mRNA helicase activity. Additionally, the cryo-EM map reveals interaction of another extracellular protein, outer membrane protein C (OmpC), with the ribosome at the peripheral solvent side of the 50S subunit. Our result also provides important insight into plausible functional role of OmpC upon ribosome binding. Visualization of the ribosome purified directly from the cell lysate unveils for the first time interactions of additional regulatory proteins with the ribosome. PMID- 26822934 TI - Ground-based assessment of JAXA mouse habitat cage unit by mouse phenotypic studies. AB - The Japan Aerospace Exploration Agency developed the mouse Habitat Cage Unit (HCU) for installation in the Cell Biology Experiment Facility (CBEF) onboard the Japanese Experimental Module ("Kibo") on the International Space Station. The CBEF provides "space-based controls" by generating artificial gravity in the HCU through a centrifuge, enabling a comparison of the biological consequences of microgravity and artificial gravity of 1 g on mice housed in space. Therefore, prior to the space experiment, a ground-based study to validate the habitability of the HCU is necessary to conduct space experiments using the HCU in the CBEF. Here, we investigated the ground-based effect of a 32-day housing period in the HCU breadboard model on male mice in comparison with the control cage mice. Morphology of skeletal muscle, the thymus, heart, and kidney, and the sperm function showed no critical abnormalities between the control mice and HCU mice. Slight but significant changes caused by the HCU itself were observed, including decreased body weight, increased weights of the thymus and gastrocnemius, reduced thickness of cortical bone of the femur, and several gene expressions from 11 tissues. Results suggest that the HCU provides acceptable conditions for mouse phenotypic analysis using CBEF in space, as long as its characteristic features are considered. Thus, the HCU is a feasible device for future space experiments. PMID- 26822935 TI - Establishment of a novel rat model of different degrees of portal vein stenosis following 70% partial hepatectomy. AB - Liver transplantation may fail due to complications of insufficient portal vein (PV) flow such as portal vein stenosis (PVS). Therefore, establishing a model to explore the effect of PV flow on liver regeneration is crucial and essential. Rats were randomly divided into 6 groups: sham operation rats group; 70% partial hepatectomy (PH) group (group A); PVS groups with mild, moderate, or severe stenosis (group B-D) and portal vein ligation (PVL) group. PVS was produced by ligating PV with parallelly placed needles of different gauges. Ultrasound was performed to validate the stenosis ratio (SR) and velocity ratio (VR) at the prestenotic and stenotic site. Rats were sacrificed on day 1,3,7, and 14 after surgery, and liver regeneration rate (LRR) was calculated. We successfully established rat models of different degrees of PVS following 70%PH in 72 rats. The SRs of each PVS group were 44.8 +/- 5.23%, 59.3 +/- 4.07% and 69.5 +/- 2.17%, which showed no statistical differences compared with those measured by stenosis ratio measured by ultrasound. The survival rate in groups A-D were 100%, 83.3%, 66.7% and 50% respectively. Differences were demonstrated between groups A and C, as well as groups A and D (both P<0.05). Moreover, LRR negatively correlated with SRu and VR, and the correlation coefficients were -0.534 and -0.522, respectively. The rat model we established has the potential to be applied in most conditions of liver regeneration with reduced PV inflow, and it provides a foundation for further exploring the relationship between PV hemodynamic changes and liver regeneration. PMID- 26822936 TI - Depth perception disorder after left ventral occipital lobe infarction. PMID- 26822937 TI - Low resting heart rate is associated with violence in late adolescence: a prospective birth cohort study in Brazil. AB - BACKGROUND: Youth violence is a major global public health problem. Three UK and Swedish studies suggest that low resting heart rate predicts male youth violence, but this has not been tested in other social settings nor for females. METHODS: A prospective, population-based birth cohort study was conducted in Pelotas, Brazil. Heart rate was measured using a wrist monitor at ages 11, 15 and 18 years. Violent crime and non-violent crime were measured at age 18 in self reports and official records (N = 3618). Confounding variables were assessed in the perinatal period and at age 11, in interviews with mothers and children. Logistic regression was used to estimate associations between quartiles of heart rate at each age, and violent and non-violent crime at age 18, separately for males and females. RESULTS: Lower resting heart rate was a robust correlate of violent and non-violent crime for males. Comparing males in the lowest and top quartiles of heart rate at age 15 years, adjusted odds ratios were 1.9 for violent crime [95% confidence interval (CI) 1.4-2.7] and 1.7 for non-violent crime (95% CI 1.1-2.6). For females, crime outcomes were associated only with low resting heart rate at age 18. Associations were generally linear across the four heart rate quartiles. There was no evidence that associations differed according to socioeconomic status at age 15. CONCLUSIONS: Low resting heart rate predicted violent and non-violent crime for males, and was cross-sectionally associated with crime for females. Biological factors may contribute to individual propensity to commit crime, even in a middle-income setting with high rates of violence. PMID- 26822938 TI - Cohort Profile: The National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea. PMID- 26822939 TI - Polygenic risk for coronary artery disease is associated with cognitive ability in older adults. AB - BACKGROUND: Coronary artery disease (CAD) is associated with cognitive decrements and risk of later dementia, but it is not known if shared genetic factors underlie this association. We tested whether polygenic risk for CAD was associated with cognitive ability in community-dwelling cohorts of middle-aged and older adults. METHODS: Individuals from Generation Scotland: Scottish Family Health Study (GS:SFHS, N = 9865) and from the Lothian Birth Cohorts of 1921 (LBC1921, N = 517) and 1936 (LBC1936, N = 1005) provided cognitive data and genome-wide genotype data. Polygenic risk profile scores for CAD were calculated for all of the cohorts using the largest available genome-wide association studies (GWAS) data set, the CARDIoGRAM consortium (22 233 cases and 64 762 controls). Polygenic risk profile scores for CAD were then tested for their association with cognitive abilities in the presence and absence of manifest cardiovascular disease. RESULTS: A meta-analysis of all three cohorts showed a negative association between CAD polygenic risk and fluid cognitive ability (beta = -0.022, P = 0.016), verbal intelligence (beta = -0.024, P = 0.011) and memory (beta = -0.021, P = 0.028). CONCLUSIONS: Increased polygenic risk for CAD is associated with lower cognitive ability in older adults. Common genetic variants may underlie some of the association between age-related cognitive decrements and the risk for CAD. PMID- 26822940 TI - High-risk older smokers' perceptions, attitudes, and beliefs about lung cancer screening. AB - The US Preventive Services Task Force recommends that smokers aged 55-80 should be screened annually with low-dose computed tomography (LDCT). This study identified demographics, smoking history, health risk perceptions, knowledge, and attitudes factors of older smokers (>=55 years) related to LDCT agreement. Using binary logistic regression, a predictive model of factors to explain LDCT agreement was produced. This is a cross-sectional, national, online survey of 338 older smokers (>=55 years) with a >=30 pack-year smoking history. Over 82% of the sample believed that a person who continues to smoke after the age of 40 has at least a 25% chance of developing lung cancer and 77.3% would "agree to a LDCT today". Using chi-square analyses, six variables that were significant at the 0.10 level were selected for inclusion in model development. Four of the independent variables made a unique statistically significant contribution to the model: perceives accuracy of the LDCT as an important factor in the decision to have a LDCT scan; believes that early detection of LC will result in a good prognosis; believes that they are at high risk for lung cancer; and is not afraid of CT scans. Of note, only 10.9% believed that a negative CT scan result would mean that they could continue to smoke. Older smokers are aware of the risks of smoking, are interested in smoking cessation, and most are interested in and positive about LDCT. Cognitive aspects of participation in screening are key to increasing the uptake of lung cancer screening among high-risk smokers. PMID- 26822941 TI - Letter Regarding: Selenium and Preeclampsia: A Systemic Review and Meta-Analysis. PMID- 26822942 TI - Skin cancer care in institutionalized elderly in the Netherlands: a nationwide study on the role of nursing home physicians. PMID- 26822943 TI - Characterizing optical properties and spatial heterogeneity of human ovarian tissue using spatial frequency domain imaging. AB - A spatial frequency domain imaging (SFDI) system was developed for characterizing ex vivo human ovarian tissue using wide-field absorption and scattering properties and their spatial heterogeneities. Based on the observed differences between absorption and scattering images of different ovarian tissue groups, six parameters were quantitatively extracted. These are the mean absorption and scattering, spatial heterogeneities of both absorption and scattering maps measured by a standard deviation, and a fitting error of a Gaussian model fitted to normalized mean Radon transform of the absorption and scattering maps. A logistic regression model was used for classification of malignant and normal ovarian tissues. A sensitivity of 95%, specificity of 100%, and area under the curve of 0.98 were obtained using six parameters extracted from the SFDI images. The preliminary results demonstrate the diagnostic potential of the SFDI method for quantitative characterization of wide-field optical properties and the spatial distribution heterogeneity of human ovarian tissue. SFDI could be an extremely robust and valuable tool for evaluation of the ovary and detection of neoplastic changes of ovarian cancer. PMID- 26822944 TI - Water relations and photosynthesis along an elevation gradient for Artemisia tridentata during an historic drought. AB - Quantifying the variation in plant-water relations and photosynthesis over environmental gradients and during unique events can provide a better understanding of vegetation patterns in a future climate. We evaluated the hypotheses that photosynthesis and plant water potential would correspond to gradients in precipitation and soil moisture during a lengthy drought, and that experimental water additions would increase photosynthesis for the widespread evergreen shrub Artemisia tridentata ssp. vaseyana. We quantified abiotic conditions and physiological characteristics for control and watered plants at 2135, 2315, and 2835 m near Mammoth Lakes, CA, USA, at the ecotone of the Sierra Nevada and Great Basin ecoregions. Snowfall, total precipitation, and soil moisture increased with elevation, but air temperature and soil N content did not. Plant water potential (Psi), stomatal conductance (g s), maximum photosynthetic rate (A max), carboxylation rate (V cmax), and electron transport rate (J max) all significantly increased with elevations. Addition of water increased Psi, g s, J max, and A max only at the lowest elevation; g s contributed about 30 % of the constraints on photosynthesis at the lowest elevation and 23 % at the other two elevations. The physiology of this foundational shrub species was quite resilient to this 1-in-1200 year drought. However, plant water potential and photosynthesis corresponded to differences in soil moisture across the gradient. Soil re-wetting in early summer increased water potential and photosynthesis at the lowest elevation. Effects on water relations and photosynthesis of this widespread, cold desert shrub species may be disproportionate at lower elevations as drought length increases in a future climate. PMID- 26822945 TI - When to suspect primary ciliary dyskinesia in children. AB - Primary ciliary dyskinesia [PCD] is an uncommon, autosomal recessively inherited condition that is often overlooked and undertreated in childhood. Amidst the myriad of children with coloured nasal secretions, otitis media and a wet cough, there exists a subset with PCD as the underlying unifying diagnosis. In this paper we have highlighted the varying clinical manifestations of PCD, emphasising different presentations between neonates, toddlers, school aged children and adults. PMID- 26822947 TI - Understanding the electromagnetic interaction of metal organic framework reactants in aqueous solution at microwave frequencies. AB - Preparation of metal organic frameworks (MOFs) via microwave heating is becoming increasingly popular due to reduced reaction times and enhanced control of MOF particle size. However, there is little understanding about the detailed interaction of the electric field portion of the wave with reactants during the synthesis of MOFs. In order to overcome this lack of fundamental understanding, information about the dielectric properties of the reactants is required. In this work the dielectric constants (epsilon') and loss factors (epsilon'') of benzene 1,4-dicarboxylic acid (H2BDC; also known as terephthalic acid) and a number of M(III) (M = metal) salts dissolved in deionized water were measured as a function of frequency, temperature and concentration and with varying anions and cations. Dielectric data confirm the aqueous M(III) salts to be strong microwave absorbers, particularly at 915 MHz. M(III) salts with mono-anionic ligands (for example chlorides and nitrates) exhibit higher losses than di-anionic salts (sulfates) demonstrating that the former are heated more effectively in an applied microwave field. Of the M(III) salts containing either singly- or doubly charged anions, those containing Fe(III) have the highest loss indicating that they will heat more efficiently than other M(III) salts such as Cr(III) and Al(III). Interestingly, H2BDC exhibits little interaction with the electric field at microwave frequencies. PMID- 26822946 TI - Intravoxel incoherent motion MRI as a biomarker of sorafenib treatment for advanced hepatocellular carcinoma: a pilot study. AB - BACKGROUND: To evaluate the association between the therapeutic outcomes of sorafenib for advanced hepatocellular carcinoma (HCC) and the parameters of intravoxel incoherent motion (IVIM). METHODS: Nine patients were evaluated prospectively. All patients were Child-Pugh score A. The mean dimension of the lesion was 32 mm (range: 15-74 mm). MR images were obtained using a 1.5-Tesla superconductive MRI system. Diffusion-weighted imaging was performed under breath holding using b-values of 0, 50, 100, 150, 200, 400, and 800 s/mm(2). The following IVIM parameters were calculated: apparent diffusion coefficient, true diffusion coefficient (DC), pseudo-diffusion coefficient, and perfusion fraction. MRI was performed before treatment and at 1, 2, and 4 weeks after beginning treatment. Tumor response at 4 weeks was assessed by CT or MRI using modified RECIST. IVIM parameters of the treatment responders and non-responders were compared. RESULTS: The DC of responders at baseline was significantly higher than that of the non-responders. The sensitivity and specificity, when a DC of 0.8 (10(-3) mm(2)/s) or higher was considered to be a responder, were 100 % and 67 %, respectively. No significant differences were found in the other parameters between the responders and the non-responders. All IVIM parameters of the responders and non-responders did not change significantly after treatment. CONCLUSION: The DC before treatment may be a useful parameter for predicting the therapeutic outcome of sorafenib for advanced HCC. PMID- 26822948 TI - How to regress and predict in a Bland-Altman plot? Review and contribution based on tolerance intervals and correlated-errors-in-variables models. AB - Two main methodologies for assessing equivalence in method-comparison studies are presented separately in the literature. The first one is the well-known and widely applied Bland-Altman approach with its agreement intervals, where two methods are considered interchangeable if their differences are not clinically significant. The second approach is based on errors-in-variables regression in a classical (X,Y) plot and focuses on confidence intervals, whereby two methods are considered equivalent when providing similar measures notwithstanding the random measurement errors. This paper reconciles these two methodologies and shows their similarities and differences using both real data and simulations. A new consistent correlated-errors-in-variables regression is introduced as the errors are shown to be correlated in the Bland-Altman plot. Indeed, the coverage probabilities collapse and the biases soar when this correlation is ignored. Novel tolerance intervals are compared with agreement intervals with or without replicated data, and novel predictive intervals are introduced to predict a single measure in an (X,Y) plot or in a Bland-Atman plot with excellent coverage probabilities. We conclude that the (correlated)-errors-in-variables regressions should not be avoided in method comparison studies, although the Bland-Altman approach is usually applied to avert their complexity. We argue that tolerance or predictive intervals are better alternatives than agreement intervals, and we provide guidelines for practitioners regarding method comparison studies. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26822950 TI - Elemental-Sulfur-Mediated Facile Synthesis of a Covalent Triazine Framework for High-Performance Lithium-Sulfur Batteries. AB - A covalent triazine framework (CTF) with embedded polymeric sulfur and a high sulfur content of 62 wt % was synthesized under catalyst- and solvent-free reaction conditions from 1,4-dicyanobenzene and elemental sulfur. Our synthetic approach introduces a new way of preparing CTFs under environmentally benign conditions by the direct utilization of elemental sulfur. The homogeneous sulfur distribution is due to the in situ formation of the framework structure, and chemical sulfur impregnation within the micropores of CTF effectively suppresses the dissolution of polysulfides into the electrolyte. Furthermore, the triazine framework facilitates electron and ion transport, which leads to a high performance lithium-sulfur battery. PMID- 26822949 TI - Hereditary truncating mutations of DNA repair and other genes in BRCA1/BRCA2/PALB2-negatively tested breast cancer patients. AB - Hereditary breast cancer comprises a minor but clinically meaningful breast cancer (BC) subgroup. Mutations in the major BC-susceptibility genes are important prognostic and predictive markers; however, their carriers represent only 25% of high-risk BC patients. To further characterize variants influencing BC risk, we performed SOLiD sequencing of 581 genes in 325 BC patients (negatively tested in previous BRCA1/BRCA2/PALB2 analyses). In 105 (32%) patients, we identified and confirmed 127 truncating variants (89 unique; nonsense, frameshift indels, and splice site), 19 patients harbored more than one truncation. Forty-six (36 unique) truncating variants in 25 DNA repair genes were found in 41 (12%) patients, including 16 variants in the Fanconi anemia (FA) genes. The most frequent variant in FA genes was c.1096_1099dupATTA in FANCL that also show a borderline association with increased BC risk in subsequent analysis of enlarged groups of BC patients and controls. Another 81 (53 unique) truncating variants were identified in 48 non-DNA repair genes in 74 patients (23%) including 16 patients carrying variants in genes coding proteins of estrogen metabolism/signaling. Our results highlight the importance of mutations in the FA genes' family, and indicate that estrogen metabolism genes may reveal a novel candidate genetic component for BC susceptibility. PMID- 26822951 TI - The ovation abdominal stent graft for the treatment of abdominal aortic aneurysms: current evidence and future perspectives. AB - The Ovation Abdominal Stent Graft System is a trimodular endoprosthesis recently introduced for the endovascular repair of abdominal aortic aneurysm (AAA). It uncouples the stages of stent-graft fixation and sealing with the suprarenal fixation achieved with a long, rigid anchored stent while the sealing onto the neck is accomplished via a pair of polymer-filled inflatable rings that accommodate to each patient's individual anatomy. Moreover, the lack of Nitinol support enables lower profiles of the endograft's delivery system, thus facilitating the navigation through angulated and stenosed iliac vessels. Ovation's novel design expands further the AAA eligibility to endovascular repair. This article discusses the clinical and hemodynamic consequences of the Ovation design and contributes to better understanding of current and future implications. PMID- 26822952 TI - Risk Factors and Clinical Impacts of Peri-Stent Contrast Staining After Second Generation Drug-Eluting Stent Implantation. AB - BACKGROUND: Peri-stent contrast staining (PSS) after sirolimus-eluting stent implantation is associated with target lesion revascularization (TLR) and very late stent thrombosis. However, the risk factors and clinical sequelae of PSS after second-generation DES implantation remain unclear. METHODS AND RESULTS: This study comprised 2,090 patients with 2,883 lesions treated with second generation DES from April 2009 to February 2013. Angiographic findings and clinical outcomes were compared between PSS and non-PSS groups. Follow-up angiography was available for 2,411 lesions. PSS was observed in 23 lesions: 4 in biolimus-eluting stents, 4 in zotarolimus-eluting stents (ZES), and 15 in everolimus-eluting stents (EES). Right coronary artery lesions, chronic total occlusion (CTO), and lesions with severe angulation (>90 degrees ) were more frequent in the PSS group compared with the non-PSS group. Lesions were longer and the cumulative TLR incidence at 3 years was higher in the PSS group than those in the non-PSS group (27.9 mm vs. 19.4 mm, P < 0.0001; 27.4% vs. 8.6%, P = 0.0002). There was no significant difference in stent thrombosis between the two groups. Multivariable analysis identified CTO [odds ratio (OR) 3.75, 95%CI 1.52 8.88, P = 0.005] as an independent predictor of PSS. CONCLUSIONS: PSS after second-generation DES implantation was associated with an increased risk of subsequent TLR. CTO was the independent predictor of PSS. PMID- 26822953 TI - High yield 1,3-propanediol production by rational engineering of the 3 hydroxypropionaldehyde bottleneck in Citrobacter werkmanii. AB - BACKGROUND: Imbalance in cofactors causing the accumulation of intermediates in biosynthesis pathways is a frequently occurring problem in metabolic engineering when optimizing a production pathway in a microorganism. In our previous study, a single knock-out Citrobacter werkmanii ?dhaD was constructed for improved 1,3 propanediol (PDO) production. Instead of an enhanced PDO concentration on this strain, the gene knock-out led to the accumulation of the toxic intermediate 3 hydroxypropionaldehyde (3-HPA). The hypothesis was emerged that the accumulation of this toxic intermediate, 3-HPA, is due to a cofactor imbalance, i.e. to the limited supply of reducing equivalents (NADH). Here, this bottleneck is alleviated by rationally engineering cell metabolism to balance the cofactor supply. RESULTS: By eliminating non-essential NADH consuming enzymes (such as lactate dehydrogenase coded by ldhA, and ethanol dehydrogenase coded by adhE) or by increasing NADH producing enzymes, the accumulation of 3-HPA is minimized. Combining the above modifications in C. werkmanii ?dhaD resulted in the strain C. werkmanii ?dhaD?ldhA?adhE::ChlFRT which provided the maximum theoretical yield of 1.00 +/- 0.03 mol PDO/mol glycerol when grown on glucose/glycerol (0.33 molar ratio) on flask scale under anaerobic conditions. On bioreactor scale, the yield decreased to 0.73 +/- 0.01 mol PDO/mol glycerol although no 3-HPA could be measured, which indicates the existence of a sink of glycerol by a putative glycerol dehydrogenase, channeling glycerol to the central metabolism. CONCLUSIONS: In this study, a multiple knock-out was created in Citrobacter species for the first time. As a result, the concentration of the toxic intermediate 3-HPA was reduced to below the detection limit and the maximal theoretical PDO yield on glycerol was reached. PMID- 26822954 TI - Athermal Azobenzene-Based Nanoimprint Lithography. AB - A novel nanoimprint lithography technique based on the photofluidization effect of azobenzene materials is presented. The tunable process allows for imprinting under ambient conditions without crosslinking reactions, so that shrinkage of the resist is avoided. Patterning of surfaces in the regime from micrometers down to 100 nm is demonstrated. PMID- 26822955 TI - Low tidal volume ventilation preconditioning ameliorates lipopolysaccharide induced acute lung injury in rats. AB - BACKGROUND: Effects of low tidal volume (LTV) ventilation preconditioning in endotoxin-induced acute lung injury (ALI) have not been studied. We investigated the effect of LTV ventilation pre-treatment on ALI induced by lipopolysaccharide (LPS) in rats. METHODS: Male Sprague-Dawley rats were assigned to four groups (n = 8 each): (1) sham rats injected (i.p.) with 0.9% (physiologic) saline; sham rats pre-treated with tidal volume 6 ml/kg ventilation for 1 h followed by injection (i.p.) of physiologic saline (mechanical ventilation; MV-saline group); (2) LPS group (rats injected with LPS (i.p.); rats pre-treated with tidal volume 6 ml/kg ventilation for 1 h before injection (i.p.) with LPS (MV-LPS group). Animals were observed for 6 h. ALI extent was evaluated by lung wet-to-dry ratio, Evans Blue Dye extravasation, and histologic examination. We measured levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. Apoptotic index (AI) and the expression of pulmonary RhoA, ROCK2 mRNA, and ROCK1 protein in lung alveolar cells was determined. RESULTS: Lipopolysaccharide caused severe ALI, as evidenced by increases in ALI extent, impairment of pulmonary functions, and increases in pulmonary levels of TNF-alpha, IL-1beta, IL-6, and AI. LTV ventilation preconditioning mitigated LPS-induced increases in release of pulmonary pro-inflammatory cytokines and AI of alveolar cells. Expression of pulmonary RhoA, ROCK2 mRNA, and ROCK1 protein was upregulated by LPS and reduced by LTV ventilation pre-treatment. CONCLUSION: Low tidal volume ventilation preconditioning can attenuate release of pulmonary pro-inflammatory cytokines and decrease the AI induced by severe sepsis. Early protection seems to be mediated partly through inhibition of activation of a Rho pathway. PMID- 26822957 TI - Isolation and Characterization of Spore-Forming Bacilli (SFB) from Shepherd's Purse (Capsella bursa-pastoris). AB - Shepherd's purse (Capsella bursa-pastoris), native to Europe, is commonly consumed fresh and sometimes inadequately washed before consumption in Korea. The objective of this study was to characterize isolates of spore-forming bacilli (SFB) in samples of fresh Shepherd's purse. Three genera were identified: Bacillus (9 species), Paenibacillus (3 species), and Brevibacillus (1 species). None of the genes of the hemolysin BL (HBL) and nonhemolytic enterotoxin (NHE) complexes, or of the emetic toxin, was detected in the 25 SFB isolates, except for 2 Bacillus pseudomycoides isolates, where all 3 genes of the HBL enterotoxin complex were detected. There were significant sequence variations between the 2 species (Bacillus cereus and B. pseudomycoides) in the 3 genes of the HBL enterotoxin complex. These findings may provide insights into the diverse characteristics of the B. pseudomycoides HBL enterotoxin complex. Antibiotic resistance was assessed using 8 antibiotics. Among the 25 SFB isolates, 11 showed resistance to antibiotics, of which 5 were multiresistant. Assessment of the spoilage potential showed that all 25 SFB isolates could produce enzymes that can cause spoilage of foods. In conclusion, our findings may serve as integrative information for food research and industrial sectors. PMID- 26822956 TI - Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells. AB - Non-CG methylation is an unexplored epigenetic hallmark of pluripotent stem cells. Here we report that a reduction in non-CG methylation is associated with impaired differentiation capacity into endodermal lineages. Genome-wide analysis of 2,670 non-CG sites in a discovery cohort of 25 phenotyped human induced pluripotent stem cell (hiPSC) lines revealed unidirectional loss (Deltabeta=13%, P<7.4 * 10(-4)) of non-CG methylation that correctly identifies endodermal differentiation capacity in 23 out of 25 (92%) hiPSC lines. Translation into a simplified assay of only nine non-CG sites maintains predictive power in the discovery cohort (Deltabeta=23%, P<9.1 * 10(-6)) and correctly identifies endodermal differentiation capacity in nine out of ten pluripotent stem cell lines in an independent replication cohort consisting of hiPSCs reprogrammed from different cell types and different delivery systems, as well as human embryonic stem cell (hESC) lines. This finding infers non-CG methylation at these sites as a biomarker when assessing endodermal differentiation capacity as a readout. PMID- 26822958 TI - Experimental feline enteric coronavirus infection reveals an aberrant infection pattern and shedding of mutants with impaired infectivity in enterocyte cultures. AB - Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection. Since many virological and immunological data on FECV infections are lacking, the present study investigated these missing links during experimental infection of three SPF cats with FECV strain UCD. Two cats showed mild clinical signs, faecal shedding of infectious virus from 4 dpi, a cell-associated viraemia at inconsistent time points from 5 dpi, a highly neutralising antibody response from 9 dpi, and no major abnormalities in leukocyte numbers. Faecal shedding lasted for 28-56 days, but virus shed during this stage was less infectious in enterocyte cultures and affected by mutations. Remarkably, in the other cat neither clinical signs nor acute shedding were seen, but virus was detected in blood cells from 3 dpi, and shedding of non-enterotropic, mutated viruses suddenly occurred from 14 dpi onwards. Neutralising antibodies arose from 21 dpi. Leukocyte numbers were not different compared to the other cats, except for the CD8(+) regulatory T cells. These data indicate that FECV can infect immune cells even in the absence of intestinal replication and raise the hypothesis that the gradual adaptation to these cells can allow non-enterotropic mutants to arise. PMID- 26822959 TI - Macrocyclic Transformations from Norrole to Isonorrole and an N-Confused Corrole with a Fused Hexacyclic Ring System Triggered by a Pyrrole Substituent. AB - Three kinds of fused porphyrinoids, L2-L4, possessing different types of corrole based frameworks were synthesized from a pyrrole-substituted corrole isomer (norrole L1). Oxidation of L1 afforded a unique N-Cmeso -fused pyrrolyl isonorrole L2, involving the fusion of an auxiliary pyrrolic NH moiety with a meso-sp(3) -hybridized carbon atom. Subsequently, L2 underwent macrocycle transformations to give singly and doubly N-CAr -fused N-confused corroles, L3 and L4, respectively. L3 and L4 contain fused [5.7.6.5]-tetra- and [5.6.7.7.6.5] hexacyclic structures, respectively, prepared through lateral annulation. These skeletal transformation reactions from norrole to its isomer isonorrole and finally to N-confused corrole indicate that multiply fused porphyrinoids could be readily synthesized from pyrrole-appended confused porphyrinoids. PMID- 26822961 TI - Is rigid endoscopy necessary with childhood corrosive ingestion? a retrospective comparative analysis of 458 cases. AB - The aim of this study was to determine the necessity of endoscopy in cases in which a corrosive substance was ingested and to find a practical way to avoid unnecessary endoscopies for similar cases in the future. The clinical records of 458 hospitalized cases with clinical histories of corrosive substance ingestion between January 2007 and December 2013 were retrospectively reviewed. The demographics of the cases, the ingested substances, and the rigid endoscopy findings were evaluated. The three most commonly ingested corrosive agents were household bleach (22.9%), household degreaser (15.9%), and drain cleaner (13.1%). Rigid esophagoscopy was performed in 367 of the 458 cases. Corrosive agents were grouped according to their purpose of household use; eight groups were created. The degree of corrosive injury observed in the different groups was compared with the degree of injury caused by household bleach. Among the corrosive agent groups, dishwashing machine products (Gr.1), laundry products (Gr.2), liquid cleaners (Gr.3), and household bleach (Gr.4) did not cause high-grade injuries. The resulting injuries and esophagoscopy results among the above groups, whether symptomatic or not, did not differ from one another. Corrosive agents such as drain cleaner (Gr.6), household degreaser (Gr.7), and several other acidic products (Gr.8) caused high-grade injuries in the esophagus; however, lime remover/HCl (Gr.5) did not. Thus, hospitalization and rigid endoscopy seem unnecessary to assess esophageal injury in most cases, if the ingested corrosive agent fits into group 1, 2, 3, or 4 and if the patient can be easily fed. Esophagoscopy is useful to shorten the hospitalization times in cases where strong corrosive agents were ingested, such as those in groups 5, 6, 7, and 8. PMID- 26822960 TI - Reorganization of Motor Cortex by Vagus Nerve Stimulation Requires Cholinergic Innervation. AB - BACKGROUND: Vagus nerve stimulation (VNS) paired with forelimb training drives robust, specific reorganization of movement representations in the motor cortex. The mechanisms that underlie VNS-dependent enhancement of map plasticity are largely unknown. The cholinergic nucleus basalis (NB) is a critical substrate in cortical plasticity, and several studies suggest that VNS activates cholinergic circuitry. OBJECTIVE: We examined whether the NB is required for VNS-dependent enhancement of map plasticity in the motor cortex. METHODS: Rats were trained to perform a lever pressing task and then received injections of the immunotoxin 192 IgG-saporin to selectively lesion cholinergic neurons of the NB. After lesion, rats underwent five days of motor training during which VNS was paired with successful trials. At the conclusion of behavioral training, intracortical microstimulation was used to document movement representations in motor cortex. RESULTS: VNS paired with forelimb training resulted in a substantial increase in the representation of proximal forelimb in rats with an intact NB compared to untrained controls. NB lesions prevent this VNS-dependent increase in proximal forelimb area and result in representations similar to untrained controls. Motor performance was similar between groups, suggesting that differences in forelimb function cannot account for the difference in proximal forelimb representation. CONCLUSIONS: Together, these findings indicate that the NB is required for VNS dependent enhancement of plasticity in the motor cortex and may provide insight into the mechanisms that underlie the benefits of VNS therapy. PMID- 26822962 TI - Anti-obesity effect of extract from fermented Curcuma longa L. through regulation of adipogenesis and lipolysis pathway in high-fat diet-induced obese rats. AB - BACKGROUND: Even though Curcuma longa L. possesses various biological activities, it has strong flavor and taste, which decrease consumer palatability and limit industrial applications in food. OBJECTIVE: The present study investigates the effects of C. longa L. fermented with Aspergillus oryzae supplementation in 60% high-fat diet-induced obese rats measured by the activation of adipogenesis and lipolysis. DESIGN: Rats were divided into four groups (n=6 per group) after 1 week of acclimatization: a normal diet group comprised rats fed the AIN76A rodent diet; a high-fat diet-induced obese group with rats fed a 60% high-fat diet; a Garcinia cambogia treated group (positive control) with rats fed a 60% high-fat diet with G. cambogia 500 g/kg body weight (b.w.)/day; and an fermented C. longa L. 50% ethanolic extract treated group (FCE50) with rats fed a 60% high-fat diet with FCE50 500 g/kg b.w./day. Each group received the appropriate vehicle or sample daily by gastric intubation for 12 weeks. RESULTS: We found that FCE50 administration suppressed b.w. gain and reduced white adipose tissue weight, serum triglyceride (TG), and cholesterol in high-fat diet-induced obese rats. These results can be associated with the suppression of adipocyte differentiation and lipogenesis with a decrease in the mRNA expressions of fatty acid synthase, acetyl-CoA carboxylase, adipocyte protein 2, and lipoprotein lipase induced by FCE50 administration. In addition, FCE50 increased lipolysis and beta-oxidation by up-regulating the expression of lipases such as adipose triglyceride lipase, hormone-sensitive lipase, adiponectin, and AMP-activated protein kinase. CONCLUSIONS: These results suggest that FCE50 can be a candidate for the prevention of obesity via suppressing adipogenesis and promoting lipolysis. PMID- 26822964 TI - Evolution of Test Methods Used for the Nutrient Analysis of Infant Formula. PMID- 26822963 TI - ShockOmics: multiscale approach to the identification of molecular biomarkers in acute heart failure induced by shock. AB - BACKGROUND: The ShockOmics study (ClinicalTrials.gov identifier NCT02141607) is a multicenter prospective observational trial aimed at identifying new biomarkers of acute heart failure in circulatory shock, by means of a multiscale analysis of blood samples and hemodynamic data from subjects with circulatory shock. METHODS AND DESIGN: Ninety septic shock and cardiogenic shock patients will be recruited in three intensive care units (ICU) (Hopital Erasme, Universite Libre de Bruxelles, Belgium; Hospital Universitari Mutua Terrassa, Spain; Hopitaux Universitaires de Geneve, Switzerland). Hemodynamic signals will be recorded every day for up to seven days from shock diagnosis (time T0). Clinical data and blood samples will be collected for analysis at: i) T1 < 16 h from T0; ii) T2 = 48 h after T0; iii) T3 = day 7 or before discharge or before discontinuation of therapy in case of fatal outcome; iv) T4 = day 100. The inclusion criteria are: shock, Sequential Organ Failure Assessment (SOFA) score > 5 and lactate levels >= 2 mmol/L. The exclusion criteria are: expected death within 24 h since ICU admission; > 4 units of red blood cells or >1 fresh frozen plasma transfused; active hematological malignancy; metastatic cancer; chronic immunodepression; pre existing end stage renal disease requiring renal replacement therapy; recent cardiac surgery; Child-Pugh C cirrhosis; terminal illness. Enrollment will be preceded by the signature of the Informed Consent by the patient or his/her relatives and by the physician in charge. Three non-shock control groups will be included in the study: a) healthy blood donors (n = 5); b) septic patients (n = 10); c) acute myocardial infarction or patients with prolonged acute arrhythmia (n = 10). The hemodynamic data will be downloaded from the ICU monitors by means of dedicated software. The blood samples will be utilized for transcriptomics, proteomics and metabolomics ("-omics") analyses. DISCUSSION: ShockOmics will provide new insights into the pathophysiological mechanisms underlying shock as well as new biomarkers for the timely diagnosis of cardiac dysfunction in shock and quantitative indices for assisting the therapeutic management of shock patients. PMID- 26822965 TI - The use of acetone to enhance the infiltration of HA nanoparticles into a demineralized dentin collagen matrix. AB - OBJECTIVES: This study investigates the role of acetone, as a carrier for nano hydroxyapatite (nano-HA) in solution, to enhance the infiltration of fully demineralized dentin with HA nanoparticles (NPs). METHODS: Dentin specimens were fully demineralized and subsequently infiltrated with two types of water-based nano-HA solutions (one containing acetone and one without). Characterization of the dentin surfaces and nano-HA particles was performed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The surface wettability and infiltration capacity of the nano-HA solutions were quantified by means of contact angle measurements and energy dispersive X-ray spectroscopy (EDS), respectively. Contact angle measurements were taken at baseline and repeated at regular intervals to assess the effect of acetone. The P and Ca levels of infiltrated dentin specimens were measured and compared to sound dentin and non-infiltrated controls. RESULTS: The presence of acetone resulted in an eight-fold decrease in the contact angles of the nano-HA solutions recorded on the surface of demineralized dentin compared to nano-HA solutions without acetone (one-way ANOVA, p<0.05). Perfect wetting of the demineralized dentin surface was achieved 5min after the application of the nano-HA solution containing acetone. Infiltration of demineralized dentin with the nano-HA solution containing acetone restored the lost mineral content by 50%, whereas the mean mineralization values for P and Ca in dentin treated with the acetone-free nano-HA solution were less than 6%. SIGNIFICANCE: Acetone was shown to act as a vehicle to enhance the capacity to infiltrate demineralized dentin with HA NPs. The successful infiltration of dentin collagen with HA NPs provides a suitable scaffold, whereby the infiltrated HA NPs have the potential to act as seeds that may initiate heterogenous mineral growth when exposed to an appropriate mineral-rich environment. PMID- 26822966 TI - An extremely low-index photonic crystal layer for enhanced light extraction from organic light-emitting diodes. AB - This paper reports organic light-emitting diodes (OLEDs) with improved light extraction fabricated by embedding an extremely low-index photonic crystal (LIPC) layer. The LIPC layer increases the optical efficiency through the reduced wave guide mode between the substrate and anode both by increased light resonance and by a strengthened diffraction effect from an extremely low-refractive-index medium, specifically a line structure composed of a vacuum gap. As a result, the current efficiency and power efficiency of the LIPC-OLEDs are 1.51 and 1.93 times higher, respectively, than the reference device at 1000 cd m(-2). Because most of the light extraction is significant, especially in the forward direction, at the specific wavelengths satisfying the Bragg's diffraction equation, it is possible to calculate the anomalous spectrum of the LIPC-OLED through the finite difference time domain (FDTD) method. PMID- 26822967 TI - Human latent inhibition and the density of predictive relationships in the context in which the target stimulus occurs. AB - In two experiments, participants were exposed to a listing of actions performed by a fictitious Mr. X, over three days of his life. For most of his actions an outcome was described, but some were not followed by any outcome. On Day 3, Mr. X performed an action (the target action) that was followed by a novel outcome. For participants in the control condition, the target action that preceded the appearance of this outcome was also novel; for participants in the latent inhibition (LI) condition, Mr. X had performed the target action on repeated occasions during Days 2 and 3, without it producing any outcome. All the participants were tested on their ability to retrieve the action performed by Mr. X prior to the target outcome. In Experiment 1, retrieval of the target action (indicating a less effective target action-outcome association) was poorer in the LI than in the control condition. In Experiment 2, reducing the proportion (the density) of nontarget actions that brought outcomes during initial training was found to reduce the size of the LI effect. These results are predicted by the account of LI put forward previously [Hall, G., & Rodriguez, G. (2010). Associative and nonassociative processes in latent inhibition: An elaboration of the Pearce-Hall model. In R. E. Lubow & I. Weiner (Eds.), Latent inhibition: Data, theories, and applications to schizophrenia (pp. 114-136). Cambridge, England: Cambridge University Press]. A high density of predictive relationships ensures strong activation of the expectancy that some outcome will occur when the target action is first presented; this facilitates the formation of a target action-no-event association during training in the LI condition, thus enhancing the LI effect. PMID- 26822968 TI - One-year mortality associated with COPD treatment: a comparison of tiotropium and long-acting beta2-agonists in three Italian regions: results from the OUTPUL study. AB - PURPOSE: Long-acting bronchodilators, i.e. beta-2-agonists (LABA) and tiotropium are commonly used in COPD treatment. Choice of a specific agent is based on effectiveness and safety. Evidence yields controversial results with respect to mortality. The present study compared one-year mortality associated to treatment with tiotropium versus LABA. METHODS: A population-based cohort study using data from Italian health information systems was performed. Patients aged 45+ years, discharged with COPD diagnosis in 2006-2009 were identified. Through record linkage with drug claims, patients who received a first prescription of LABA or tiotropium within 6 months after discharge were enrolled. The main analysis was restricted to naive users (no prior use of either LABA or tiotropium). We used 'intention to treat' (ITT) and 'as treated' (AT) approaches. We followed patients for a maximum of 12 months. Hazard ratios (HRs) were calculated by Cox regression including quintiles of propensity score. In sensitivity analysis patients receiving tiotropium + LABA combination were included in the tiotropium group. RESULTS: Among the 33 891 enrolees, 28% were exposed to Tio, 56% to LABA, 16% to both. Overall mean age was 74 years and the mortality rate was 122/1000 person years (py) at the ITT analysis and 108/1000 py at the AT analysis. The adjusted HR for tiotropium only compared with LABA only was 1.06 (95%CI: 0.94-1.20) at the ITT analysis and 1.00 (95%CI: 0.93-1.08) at the AT analysis. Results were robust in sensitivity analysis. CONCLUSIONS: In this real-world study use of tiotropium was not associated with an increased risk of one-year mortality compared with LABA. (c) 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID- 26822970 TI - Inflammatory effects of extracorporeal circulation. PMID- 26822969 TI - The Relationship Between Training Load and Injury, Illness and Soreness: A Systematic and Literature Review. AB - BACKGROUND: Clinically it is understood that rapid increases in training loads expose an athlete to an increased risk of injury; however, there are no systematic reviews to qualify this statement. OBJECTIVE: The aim of this systematic review was to determine training and competition loads, and the relationship between injury, illness and soreness. METHODS: The MEDLINE, SPORTDiscus, CINAHL and EMBASE databases were searched using a predefined search strategy. Studies were included if they analysed the relationship between training or competition loads and injury or illness, and were published prior to October 2015. Participants were athletes of any age or level of competition. The quality of the studies included in the review was evaluated using the Newcastle Ottawa Scale (NOS). The level of evidence was defined as strong, 'consistent findings among multiple high-quality randomised controlled trials (RCTs)'; moderate, 'consistent findings among multiple low-quality RCTs and/or non randomised controlled trials (CCTs) and/or one high-quality RCT'; limited, 'one low-quality RCT and/or CCTs, conflicting evidence'; conflicting, 'inconsistent findings among multiple trials (RCTs and/or CCTs)'; or no evidence, 'no RCTs or CCTs'. RESULTS: A total of 799 studies were identified; 23 studies met the inclusion criteria, and a further 12 studies that were not identified in the search but met the inclusion criteria were subsequently added to the review. The largest number of studies evaluated the relationship between injuries and training load in rugby league players (n = 9) followed by cricket (n = 5), football (n = 3), Australian Football (n = 3), rugby union (n = 2),volleyball (n = 2), baseball (n = 2), water polo (n = 1), rowing (n = 1), basketball (n = 1), swimming (n = 1), middle-distance runners (n = 1) and various sports combined (n = 1). Moderate evidence for a significant relationship was observed between training loads and injury incidence in the majority of studies (n = 27, 93 %). In addition, moderate evidence exists for a significant relationship between training loads and illness incidence (n = 6, 75 %). Training loads were reported to have a protective effect against injury (n = 9, 31 %) and illness (n = 1, 13 %). The median (range) NOS score for injury and illness was 8 (5-9) and 6 (5-9), respectively. LIMITATIONS: A limitation of this systematic review was the a priori search strategy. Twelve further studies were included that were not identified in the search strategy, thus potentially introducing bias. The quality assessment was completed by only one author. CONCLUSIONS: The results of this systematic review highlight that there is emerging moderate evidence for the relationship between the training load applied to an athlete and the occurrence of injury and illness. IMPLICATIONS: The training load applied to an athlete appears to be related to their risk of injury and/or illness. Sports science and medicine professionals working with athletes should monitor this load and avoid acute spikes in loads. It is recommended that internal load as the product of the rate of perceived exertion (10-point modified Borg) and duration be used when determining injury risk in team-based sports. External loads measured as throw counts should also be monitored and collected across a season to determine injury risk in throwing populations. Global positioning system-derived distances should be utilised in team sports, and injury monitoring should occur for at least 4 weeks after spikes in loads. PMID- 26822971 TI - Assessment of cytotoxicity and genotoxicity of stem bark extracts from Canarium odontophyllum Miq. (dabai) against HCT 116 human colorectal cancer cell line. AB - BACKGROUND: Canarium odontophyllum Miq. is a plant species widely known as 'dabai' and can be vastly found in Sarawak. The aim of this study was to assess the cytotoxic and genotoxic effect of extracts from stem bark of C. odontophyllum against HCT 116 human colorectal cancer cell line. METHOD: The IC50 values of the aqueous, methanol, and acetone extracts against HCT 116 cells as well as the acetone extract against human colon fibroblast cell line CCD-18co were determined using the MTT assay. The concentration of the extracts ranged from 12.5 to 200 MUg/ml at treatment time of 24, 48 and 72 h. Annexin V-FITC/PI labelling assay was employed to determine mode of HCT 116 cell death induced by acetone extract at 48 h. The DNA damage induced by the extract in HCT 116 cells was detected using alkaline comet assay at 30 min of IC10 and IC25 treatment. RESULTS: Acetone extract exhibited the highest cytotoxic effect against HCT 116 cells compared to methanol and aqueous extract at 24, 48 and 72 h. Despite no cytotoxic effect by acetone extract against CCD-18co cells at 24 and 48 h, however at 72 h, CCD-18co cells proliferated. Apoptosis assessment using Annexin V-FITC/PI labelling assay revealed that the primary cell death was via apoptosis after 48 h treatment. Low doses of acetone extract from stem bark of C. odontophyllum showed significant DNA damage in HCT 116 cells with tail moment of 6.187 +/- 0.718 A.U and 7.877 +/- 0.142 A.U, respectively. CONCLUSIONS: Acetone extract from stem bark of C. odontophyllum has high potential in the development of anticancer agent against HCT 116 cells with no cytotoxic effect against human colon fibroblast cells. PMID- 26822972 TI - High-responsivity UV-Vis Photodetector Based on Transferable WS2 Film Deposited by Magnetron Sputtering. AB - The two-dimensional layered semiconducting tungsten disulfide (WS2) film exhibits great promising prospects in the photoelectrical applications because of its unique photoelectrical conversion property. Herein, in this paper, we report the simple and scalable fabrication of homogeneous, large-size and transferable WS2 films with tens-of-nanometers thickness through magnetron sputtering and post annealing process. The produced WS2 films with low resistance (4.2 kOmega) are used to fabricate broadband sensitive photodetectors in the ultraviolet to visible region. The photodetectors exhibit excellent photoresponse properties, with a high responsivity of 53.3 A/W and a high detectivity of 1.22 * 10(11) Jones at 365 nm. The strategy reported paves new way towards the large scale growth of transferable high quality, uniform WS2 films for various important applications including high performance photodetectors, solar cell, photoelectrochemical cell and so on. PMID- 26822974 TI - The effects of smoking on dry eye parameters in healthy women. AB - AIM: To investigate the effects of chronic smoking on dry eye parameters. METHODS: Ocular surface disease index (OSDI) and tear function tests such as Schirmer's test, tear break-up-time (TBUT) test and impression cytology of 63 female chronic smokers and 40 age-matched female non-smokers were analyzed statistically. RESULTS: The mean OSDI scores, Schirmer test results and TBUT levels were 35.85 +/- 24.01 point, 14.25 +/- 5.94 mm and 5.17 +/- 2.85 s in chronic smokers and 15.20 +/- 12.93 point, 15.48 +/- 7.01 mm and 10.03 +/- 3.44 s in non-smokers, respectively. Differences in OSDI scores, TBUT levels and impression cytology grades among the chronic smokers and non-smokers were statistically significant. CONCLUSION: Smoking behavior seems to affect the dry eye parameters negatively. PMID- 26822973 TI - Use of metaphors about exome and whole genome sequencing. AB - Clinical and research uses of exome and whole genome sequencing (ES/WGS) are growing rapidly. An enhanced understanding of how individuals conceptualize and communicate about sequencing results is needed to ensure effective, mutual exchange of information between care providers and patients and between researchers and participants. Focus groups and interviews participants were recruited to discuss their attitudes and preferences for receiving hypothetical results from ES/WGS. African Americans were intentionally oversampled. We qualitatively analyzed participants' speech to identify unsolicited metaphorical language pertaining to genes and health, and grouped these occurrences into metaphorical concepts. Participants compared genetic information to physical objects including tools, weapons, contents of boxes, and formal documents or reports. These metaphorical concepts centered on several key themes, including locus of control; containment versus release of information; and desirability, usability, interpretability, and ownership of genetic results. Metaphorical language is often used intentionally or unintentionally in discussions about receiving results from ES/WGS in both clinical and research settings. Awareness of the use of metaphorical language and attention to its varied meanings facilitates effective communication about return of ES/WGS results. In turn, both should foster shared and informed decision-making and improve the translation of genetic information by clinicians and researchers. PMID- 26822975 TI - Formation of a quantum spin Hall state on a Ge(111) surface. AB - Using first-principles density functional theory (DFT) hybrid functional calculations, we demonstrate the formation of a quantum spin Hall (QSH) state on a Ge(111) surface. We show that a 1/3 monolayer (ML) Cl-covered Ge(111) surface offers an ideal template for metal, such as Bi, deposition into a stable hexagonal overlayer 2D lattice, which we refer to as Bi@Cl-Ge(111). The band structure and band topology of Bi@Cl-Ge(111) are analyzed with respect to the effect of spin-orbit coupling (SOC). The Bi@Cl-Ge(111) exhibits a QSH state with a band gap of 0.54 eV. In contrast, the Au@Cl-Ge(111) is found to be a trivial semiconducting surface. The Ge(111) substrate acts as an orbital filter to critically select the orbital composition around the Fermi level. Our findings offer another possible system for experimental exploration of the growth of 2D topological materials on conventional semiconductor substrates, where the 2D overlayer is atomically bonded to, but electronically decoupled from, the underlying substrate, exhibiting an isolated topological quantum state inside the substrate band gap. PMID- 26822976 TI - Knockdown of alpha-synuclein in cerebral cortex improves neural behavior associated with apoptotic inhibition and neurotrophin expression in spinal cord transected rats. AB - Spinal cord injury (SCI) often causes severe functional impairment with poor recovery. The treatment, however, is far from satisfaction, and the mechanisms remain unclear. By using proteomics and western blot, we found spinal cord transection (SCT) resulted in a significant down-regulation of alpha-synuclein (SNCA) in the motor cortex of SCT rats at 3 days post-operation. In order to detect the role of SNCA, we used SNCA-ORF/shRNA lentivirus to upregulate or knockdown SNCA expression. In vivo, SNCA-shRNA lentivirus injection into the cerebral cortex motor area not only inhibited SNCA expression, but also significantly enhanced neurons' survival, and attenuated neuronal apoptosis, as well as promoted motor and sensory function recovery in hind limbs. While, overexpression SNCA exhibited the opposite effects. In vitro, cortical neurons transfected with SNCA-shRNA lentivirus gave rise to an optimal neuronal survival and neurite outgrowth, while it was accompanied by reverse efficiency in SNCA-ORF group. In molecular level, SNCA silence induced the upregulation of Bcl-2 and the downregulation of Bax, and the expression of NGF, BDNF and NT3 was substantially upregulated in cortical neurons. Together, endogenous SNCA play a crucial role in motor and sensory function regulation, in which, the underlying mechanism may be linked to the regulation of apoptosis associated with apoptotic gene (Bax, Bcl2) and neurotrophic factors expression (NGF, BDNF and NT3). These finds provide novel insights to understand the role of SNCA in cerebral cortex after SCT, and it may be as a novel treatment target for SCI repair in future clinic trials. PMID- 26822977 TI - Erratum to: Phosphocreatine protects against LPS-induced human umbilical vein endothelial cell apoptosis by regulating mitochondrial oxidative phosphorylation. AB - The original version of this article unfortunately contained a mistake. The arrow marks in Fig. 5 were incorrect. It is now corrected with this erratum. The correct version of Fig. 5 is given below. The authors apologise for this error and the inconvenience it has caused to the readers. PMID- 26822978 TI - Can tumor cells proliferate without ERK5? PMID- 26822979 TI - Determination of Free and Total Choline and Carnitine in Infant Formula and Adult/Pediatric Nutritional Formula by Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS): Single-Laboratory Validation, First Action 2015.10. AB - Analytical methods for the analysis of both L-carnitine and choline are needed for reliable and accurate determination in infant formula and adult/pediatric nutritional formula. These compounds are different in how they are utilized by the human body, but are structurally similar. L-carnitine and choline are quaternary ammonium compounds, enabling both to be retained under acidic conditions with strong cation exchange (SCX) chromatography. This method analyzes both compounds simultaneously as either the free forms or as a total amount that includes bound sources such as phosphatidylcholine or acetylcarnitine. The free analysis consists of water extraction and analysis by LC/MS/MS, while the total analysis consists of extraction by acid assisted microwave hydrolysis and analysis by LC/MS/MS. Calibration standards used for calculations are extracted with all samples in the batch. A single laboratory validation (SLV) was performed following the guidelines of the AOAC Stakeholder Panel on Infant Formula and Adult Nutritionals (SPIFAN) utilizing the kit of materials provided. The results achieved meet the requirements of SMPR 2012.010 and 2012.013 for L-carnitine and total choline, respectively. PMID- 26822980 TI - Lomentospora prolificans endocarditis--case report and literature review. AB - BACKGROUND: Lomentospora prolificans (formally Scedosporium prolificans) is an environmental mould with a global distribution. Endocarditis caused by L. prolificans is a rare but serious emerging disease in immunocompromised patients. Prior to this case there have only been eight cases reported in the literature. Diagnosis can be challenging and there are no evidence-based guidelines for treatment. CASE PRESENTATION: We report a 75-year-old woman with ovarian carcinoma who presented with fever after chemotherapy. Repeated sterile site cultures remained negative until day 22 of admission, when Lomentospora prolificans was isolated from blood cultures. Following extensive investigations, including Fluoro-D-glucose positron emission tomography (FDG-PET) and transoephageal echocardiography (TOE), the patient was diagnosed with endocarditis complicated by cerebral emboli. The patient was considered unsuitable for surgical intervention and passed away five days after the fungus was isolated. CONCLUSION: Endocarditis caused by Lomentospora prolificans is a rare but emerging condition, with limited treatment options and a high mortality. Awareness of the increasing incidence of Lomentospora prolificans infection, diagnosed often at an advanced stage, with potential for endocarditis may prompt earlier echocardiography or FDG-PET imaging. Further studies are needed to determine the optimal combination and duration of anti-fungal agents, used in conjunction with aggressive surgical excision where feasible. PMID- 26822981 TI - Low uptake of postpartum screening for Type 2 diabetes in women after a diagnosis of gestational diabetes. PMID- 26822983 TI - Decide the Academy's Future: Vote. PMID- 26822984 TI - Coming Together to Communicate the 2015-2020 Dietary Guidelines for Americans. PMID- 26822982 TI - Strong Hearts, healthy communities: a rural community-based cardiovascular disease prevention program. AB - BACKGROUND: Cardiovascular disease is the leading cause of death in the United States and places substantial burden on the health care system. Rural populations, especially women, have considerably higher rates of cardiovascular disease, influenced by poverty, environmental factors, access to health care, and social and cultural attitudes and norms. METHODS/DESIGN: This community-based study will be a two-arm randomized controlled efficacy trial comparing a multi level, community program (Strong Hearts, Healthy Communities) with a minimal intervention control program (Strong Hearts, Healthy Women). Strong Hearts, Healthy Communities was developed by integrating content from three evidence based programs and was informed by extensive formative research (e.g. community assessments, focus groups, and key informant interviews). Classes will meet twice weekly for one hour for 24 weeks and focus on individual-level skill building and behavior change; social and civic engagement are also core programmatic elements. Strong Hearts, Healthy Women will meet monthly for hour-long sessions over the 24 weeks covering similar content in a general, condensed format. Overweight, sedentary women 40 years of age and older from rural, medically underserved communities (12 in Montana and 4 in New York) will be recruited; sites, pair matched based on rurality, will be randomized to full or minimal intervention. Data will be collected at baseline, midpoint, intervention completion, and six month, one-year, and eighteen months post-intervention. The primary outcome is change in body weight; secondary outcomes include physiologic, anthropometric, behavioral, and psychosocial variables. In the full intervention, engagement of participants' friends and family members in partnered activities and community events is an intervention target, hypothesizing that there will be a reciprocal influence of physical activity and diet behavior between participants and their social network. Family members and/or friends will be invited to complete baseline and follow-up questionnaires about their health behaviors and environment, height and weight, and attitudes and beliefs. DISCUSSION: Strong Hearts, Healthy Communities aims to reduce cardiovascular disease morbidity and mortality, improve quality of life, and reduce cardiovascular disease-related health care burden in underserved rural communities. If successful, the long-term goal is for the program to be nationally disseminated, providing a feasible model to reduce cardiovascular disease in rural settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02499731 Registered on July 1, 2015. PMID- 26822985 TI - Academy of Nutrition and Dietetics Methodology for Conducting Systematic Reviews for the Evidence Analysis Library. PMID- 26822986 TI - 2015 Lenna Frances Cooper Memorial Lecture: Success in Dietetics: Inspired by Farmers, Flavor, and Fun! PMID- 26822987 TI - Position and Practice Paper Update for 2016. PMID- 26822988 TI - Is Dietary Fiber Considered an Essential Nutrient? PMID- 26822989 TI - Hydroxylation versus Halogenation of Aliphatic C-H Bonds by a Dioxygen-Derived Iron-Oxygen Oxidant: Functional Mimicking of Iron Halogenases. AB - An iron-oxygen intermediate species generated in situ in the reductive activation of dioxygen by an iron(II)-benzilate complex of a monoanionic facial N3 ligand, promoted the halogenation of aliphatic C-H bonds in the presence of a protic acid and a halide anion. An electrophilic iron(IV)-oxo oxidant with a coordinated halide is proposed as the active oxidant. The halogenation reaction with dioxygen and the iron complex mimics the activity of non-heme iron halogenases. PMID- 26822990 TI - 2-stage revision of 120 deep infected hip and knee prostheses using gentamicin PMMA beads. AB - Background and purpose - A 2-stage revision is the most common treatment for late deep prosthesis-related infections and in all cases of septic loosening. However, there is no consensus about the optimal interval between the 2 stages. Patients and methods - We retrospectively studied 120 deep infections of total hip (n = 95) and knee (n = 25) prostheses that had occurred over a period of 25 years. The mean follow-up time was 5 (2-20) years. All infections had been treated with extraction, 1 or more debridements with systemic antibiotics, and implantation of gentamicin-PMMA beads. There had been different time intervals between extraction and reimplantation: median 14 (11-47) days for short-term treatment with uninterrupted hospital stay, and 7 (3-22) months for long-term treatment with temporary discharge. We analyzed the outcome regarding resolution of the infection and clinical results. Results - 88% (105/120) of the infections healed, with no difference in healing rate between short- and long-term treatment. 82 prostheses were reimplanted. In the most recent decade, we treated patients more often with a long-term treatment but reduced the length of time between the extraction and the reimplantation. More reimplantations were performed in long term treatments than in short-term treatments, despite more having difficult-to treat infections with worse soft-tissue condition. Interpretation - Patient, wound, and infection considerations resulted in an individualized treatment with different intervals between stages. The 2-stage revision treatment in combination with local gentamicin-PMMA beads gave good results even with difficult prosthesis infections and gentamicin-resistant bacteria. PMID- 26822991 TI - Monitoring subnational regional inequalities in health: measurement approaches and challenges. AB - BACKGROUND: Monitoring inequalities based on subnational regions is a useful practice to unmask geographical differences in health, and deploy targeted, equity-oriented interventions. Our objective is to describe, compare and contrast current methods of measuring subnational regional inequality. We apply a selection of summary measures to empirical data from four low- or middle-income countries to highlight the characteristics and overall performance of the different measures. METHODS: We use data from Demographic and Health Surveys conducted in Bangladesh, Egypt, Ghana and Zimbabwe to calculate subnational regional inequality estimates for reproductive, maternal, newborn, and child health services generated from 11 summary measures: pairwise measures included high to low absolute difference, high to low relative difference, and high to low ratio; complex measures included population attributable risk, weighted variance, absolute weighted mean difference from overall mean, index of dissimilarity, Theil index, population attributable risk percentage, coefficient of variation, and relative weighted mean difference from overall mean. Four of these summary measures (high to low absolute difference, high to low ratio, absolute weighted mean difference from overall mean, and relative weighted mean difference from overall mean) were selected to compare their performance in measuring trend over time in inequality for one health indicator. RESULTS: Overall, the 11 different measures were more remarkable for their similarities than for their differences. Pairwise measures tended to support the same conclusions as complex summary measures-that is, by identifying same best and worst coverage indicators in each country and indicating similar time trends. Complex measures may be useful to illustrate more nuanced results in countries with a great number of subnational regions. CONCLUSIONS: When pairwise and complex measures lead to the same conclusions about the state of subnational regional inequality, pairwise measures may be sufficient for reporting inequality. In cases where complex measures are required, mean difference from mean measures can be easily communicated to non technical audiences. PMID- 26822993 TI - New era of integrated cancer biomarker discovery using reverse-phase protein arrays. AB - The ultimate goal of cancer biomarker discovery is to use individual patient derived biochemical information to improve patients' outcomes. A recent increase in the spectrum of therapeutic options for cancer requires improved approaches to identify patients likely to benefit from them. The ability to elucidate biological characteristics of tumors and to understand both inter and intra tumoral heterogeneity using large-scale data sets generated from both model systems and patient samples provides a unique opportunity to identify useful cancer biomarkers. Since the reverse-phase protein array (RPPA) was introduced in the early 2000s, it has played a central role in a wide range of uses including cancer biology, biomarker discovery, and therapeutic target evaluation. The quantitative output from RPPAs is readily combined with that from other "omics" platforms using a variety of information-intensive approaches at the molecular and population levels. A vast and rapidly growing body of related proteomic is now publicly available, and leading researchers in the field organized the Global RPPA Society in 2011 to facilitate the sharing of resources and data. The RPPA community is embracing the new paradigm of data sharing, which is designed to accelerate the discovery of cancer biomarkers and implementation of them in cancer patient management. PMID- 26822992 TI - Signatures of early frailty in the gut microbiota. AB - BACKGROUND: Frailty is arguably the biggest problem associated with population ageing, and associates with gut microbiome composition in elderly and care dependent individuals. Here we characterize frailty associations with the gut microbiota in a younger community dwelling population, to identify targets for intervention to encourage healthy ageing. METHOD: We analysed 16S rRNA gene sequence data derived from faecal samples obtained from 728 female twins. Frailty was quantified using a frailty index (FI). Mixed effects models were used to identify associations with diversity, operational taxonomic units (OTUs) and taxa. OTU associations were replicated in the Eldermet cohort. Phenotypes were correlated with modules of OTUs collapsed by co-occurrence. RESULTS: Frailty negatively associated with alpha diversity of the gut microbiota. Models considering a number of covariates identified 637 OTUs associated with FI. Twenty two OTU associations were significant independent of alpha diversity. Species more abundant with frailty included Eubacterium dolichum and Eggerthella lenta. A Faecalibacterium prausnitzii OTU was less abundant in frailer individuals, and retained significance in discordant twin analysis. Sixty OTU associations were replicated in the Eldermet cohort. OTU co-occurrence modules had mutually exclusive associations between frailty and alpha diversity. CONCLUSIONS: There was a striking negative association between frailty and gut microbiota diversity, underpinned by specific taxonomic associations. Whether these relationships are causal or consequential is unknown. Nevertheless, they represent targets for diagnostic surveillance, or for intervention studies to improve vitality in ageing. PMID- 26822995 TI - Rapid palatal expander vs. quad-helix in the orthodontic treatment of cleft lip and palate patients. AB - BACKGROUND: The purpose of this study was to compare the results obtained using the rapid palate expander (RPE) and the quad-helix (QH) in the treatment of cleft lip and palate (CLP) patients in mixed dentition. METHODS: In this retrospective clinical trial 28 CLP patients in mixed dentition were enrolled and divided into a group RPE, consisting of 11 patients, and a group QH, consisting of 17 patients. Plaster models before and after treatment were scanned and measurements were made using the software Ortho Analyzer. Measurements, obtained with a digital gauge on plaster models, were regarded as the gold standard and compared with those on digital models. Measurement error was assessed using the Dahlberg formula and the reliability and accuracy of the measurements were evaluated by the interclass coefficient (ICC). The unpaired t-test was used to compare the group RPE with the group QH. RESULTS: Measurement error found with Dahlberg's method was 0.36. ICC values indicated a strong repeatability of the evaluator's measurements on digital models and an almost perfect repeatability on plaster models, with a value of 0.79 and 0.93, respectively. The ICC for the accuracy of the measurements on digital models was equal to 0.74, indicating a strong agreement with measurements realized on plaster models. Patients in the QH group presented a gain of the anterior palatal diameter significantly greater than those in the RPE group. CONCLUSIONS: The use in mixed dentition of the quad-helix allows obtaining a greater gain of the anterior palatal diameter and a greater symmetry of the dental arch. PMID- 26822994 TI - Relationship between regulatory T cells subsets and lipid profile in dyslipidemic patients: a longitudinal study during atorvastatin treatment. AB - BACKGROUND: The CD4+ T-lymphocytes and their subtype CD4 + CD25(high)FoxP3+ regulatory T cells are receiving growing interest as major regulators of atherogenesis. We sought to investigate 1) whether the CD4 + cell subsets were expressed differently in dyslipidemic patients (Pts) and healthy subjects (HS) and 2) whether atorvastatin treatment could be associated in-vivo and in-vitro with cell changes in expression and functional response. METHODS: CD4+ subsets frequency (CD4 + CD25(high)FoxP3+, CD4 + CD25-FoxP3+) and mRNA expression for FoxP3, IL-10 and TGF-beta were evaluated in 30 consecutive Pts at baseline and after a 3-month atorvastatin therapy, and in 17 HS. RESULTS: The % of CD4 + cells did not differ between HS and Pts. The % of CD4 + CD25(high)FoxP3+ was higher in Pts than HS and did not change during treatment. The CD4 + CD25-FoxP3+ cells were similar between the two groups and were lower in Pts at visit 2. Cytokine expression and FoxP3 did not differ in HS and Pts and no substantial change was observed during treatment. At visit 1, CD4 + CD25(high)FoxP3+ cells were significantly correlated with both total-cholesterol (r = 0.570, P = 0.0002), LDL cholesterol (r = 0.715, P = 0.0001), Apolipoprotein B (r = 0.590, P = 0.0001). In vitro atorvastatin (up to 5 MUM) failed to induce any significant modulation of cell functions. CONCLUSION: CD4 + CD25(high)FoxP3+ regulatory cells seem to be over-stimulated in the early pre-clinical phase of atherosclerosis and a relationship exists between their frequency and circulating lipids. A potential immuno-modulation by statin treatment is not achieved through a normalization in peripheral CD4 + cell subsets. PMID- 26822996 TI - Assessment of wild leafy vegetables traditionally consumed by the ethnic communities of Manipur, northeast India. AB - BACKGROUND: The NE region of India falls in the global hotspot of biodiversity. Wild edible plants (WEPs) are widely consumed in the daily diet of the local people. WEPs are critical for the sustenance of ethnic communities and also as a source of income. However, WEPs received a little attention in research activities, economic development, biodiversity conservation and sustainable management. Many are largely ignored and remained unexplored. With a view of reducing the gap in traditional knowledge and tapping the hidden potential resources for proper utilization, exploitation, and sustainable management of WEPs are crucial. METHODS: Surveys were conducted at 20 major markets in all districts of Manipur throughout different seasons from August 2012 to March 2014. A total of 154 avid plant collectors and sellers were interviewed using semi structured questionnaire, formal, informal and extensive interactions to gather detailed information about these species. An integrated assessment of 68 wild leafy vegetables was also carried out to prioritize them for proper exploitation, conservation, and sustainable management. RESULTS: A total of 68 wild edible vegetables belonging to 42 families were documented which are being used by indigenous communities for nutritive and therapeutic purposes. Of these species, 54 are perennial (79 %) while others are annual (19 %). Herbaceous plants make up the highest proportion of edible plants. Leaves are dominant edible part followed by shoot and stem, and most are consumed through cooked food. Further, 57 species (84 %) are commonly available, and 11 (16 %) are rare. According to integrated assessment, 2 species have highest integrated value, 26 species have high value, 31 species have general value and 9 species are of low value. The majority of the species have a high or general value. CONCLUSION: Manipur has rich wild vegetable resources. However, many of them are seldom collected or cultivated given their importance in sustaining and diversifying diet. A comprehensive assessment indicated that majority of these plants have high value. Priority species require further research into their nutritional components to understand the potential as a source of future food and nutritional security. They should be promoted for integration into the agricultural system and income generation for local sustenance. PMID- 26822997 TI - The role of environmental factors for the composition of microbial communities of saline lakes in the Novosibirsk region (Russia). AB - BACKGROUND: Nothing is currently known about microbial composition of saline lakes of the Novosibirsk region and its dependence on physical-chemical parameters of waters. We studied the structure of microbial communities of saline lakes of the Novosibirsk region and the effect of physical-chemical parameters of waters on microbial communities of these lakes. RESULTS: According to the ion content, the lakes were classified either as chloride or chloride-sulfate types. Water salinity ranges from 4.3 to 290 g L(-1). Many diverse microbial communities were found. Filamentous and colonial Cyanobacteria of the genera Scytonema, Aphanocapsa, and/or filamentous Algae dominated in littoral communities. Spatial and temporal organization of planktonic microbial communities and the quantities of Archaea and Bacteria were investigated using fluorescent in situ hybridization. We have found that the dominant planktonic component is represented by Archaea, or, less frequently, by Bacteria. Various phylogenetic groups (Bacteria, Archaea, Algae, and Cyanobacteria) are nonuniformly distributed. The principal component analysis was used to detect environmental factors that affect microorganism abundance. We found the principal components responsible for 71.1 % of the observed variation. It was demonstrated that two block partial least squares was a better method than principal component analysis for analysis of the data. We observed general relationships between microbial abundance and water salinity. CONCLUSIONS: We have performed the first-ever study of the structure of the microbial communities of eleven saline lakes in the Novosibirsk region along with their physical-chemical parameters of waters. Our study demonstrates that saline lakes in the Novosibirsk region contain a unique microbial communities that may become a prolific source of microorganisms for fundamental and applied studies in various fields of ecology, microbiology, geochemistry, and biotechnology, and deserve further metagenomic investigation. PMID- 26822998 TI - Activation, activity and inactivation of factor VIII in factor VIII products. AB - INTRODUCTION: Factor VIII (FVIII) products used in haemophilia A treatment show inter-and intra-product and inter-assay differences in specific activity. The mechanistic basis of these differences remains unclear. AIM: The aim of this study was to mechanistically compare the functional properties of an in-house excipient-free full-length FVIII standard and pharmacologic recombinant products containing full-length (products A and B) or B-domainless (C and D) FVIII. METHODS: Factor VIII protein concentration was quantitated by ELISA. Product potency determinations (APTT, intrinsic tenase assays) and kinetic analyses detailing these products' activations by thrombin and FXa, their spontaneous and activated protein C (APC) catalysed inactivation and their performances in coagulation proteome reconstructions were studied +/- von Willebrand factor (VWF). Computational models were developed to facilitate interpretation of empirical data. RESULTS: Factor VIII protein content per manufacturer activity unit was highest for product C with the other three products similar to the standard. Potency estimates, done five different ways, varied 20-30% in inter- and intra-assay comparisons, with product B consistently showing lower specific activity. Kinetic analyses showed the five FVIII species to differ somewhat in maximum rate of activation, the maximum level of activity achieved, the rate of spontaneous or APC catalysed inactivation and the magnitude of the effect of VWF on these parameters. When evaluated both computationally and empirically in the context of tissue factor initiated thrombin generation, product C appears the most dissimilar. CONCLUSION: Assessments of FVIII activation/inactivation dynamics report larger differences between FVIII products than standard functional assays. However, all FVIII products promote a 'normal' thrombin generation response to TF. PMID- 26822999 TI - Localised excitation of a single photon source by a nanowaveguide. AB - Nowadays, integrated photonics is a key technology in quantum information processing (QIP) but achieving all-optical buses for quantum networks with efficient integration of single photon emitters remains a challenge. Photonic crystals and cavities are good candidates but do not tackle how to effectively address a nanoscale emitter. Using a nanowire nanowaveguide, we realise an hybrid nanodevice which locally excites a single photon source (SPS). The nanowire acts as a passive or active sub-wavelength waveguide to excite the quantum emitter. Our results show that localised excitation of a SPS is possible and is compared with free-space excitation. Our proof of principle experiment presents an absolute addressing efficiency etaa ~ 10(-4) only ~50% lower than the one using free-space optics. This important step demonstrates that sufficient guided light in a nanowaveguide made of a semiconductor nanowire is achievable to excite a single photon source. We accomplish a hybrid system offering great potentials for electrically driven SPSs and efficient single photon collection and detection, opening the way for optimum absorption/emission of nanoscale emitters. We also discuss how to improve the addressing efficiency of a dipolar nanoscale emitter with our system. PMID- 26823000 TI - Fosfomycin should not be first line treatment for uncomplicated urinary tract infection. PMID- 26823001 TI - Selection of food combinations to optimize survival, growth, and reproduction of the amphipod Hyalella azteca in static-renewal, water-only laboratory exposures. AB - Although standardized sediment toxicity testing methods have been developed for the amphipod Hyalella azteca, no standardized chronic water-only toxicity testing methods have been established. Furthermore, optimal feeding and water quality conditions for culturing and toxicity testing with this species remained unclear. The objective of the present study was to determine the food or combination of foods that best promotes survival, growth, and reproduction of the US Lab strain of Hyalella azteca under 42-d, water-only, static-renewal testing conditions. The authors conducted 7 42-d control (no toxicant) tests with various combinations of food (including Tetramin, yeast-cereal leaves-trout chow, diatoms, wheatgrass, alfalfa, and maple leaves) and substrate types (clean "unconditioned" Nitex screens vs "conditioned" Nitex screens that were colonized by live biofilms). Over all treatments, survival ranged from 18% to 96%, dry weight per individual from 0.084 mg to 1.101 mg, and reproduction from 0 young/female to 28.4 young/female. Treatments that included Tetramin tended to result in better performance than those that did not. In particular, treatments that included Tetramin and either conditioned screens or diatoms consistently had high survival, weight, and reproduction values as well as low variability among replicates (measured as coefficient of variation). A ramped Tetramin plus diatom suspension feeding regime appears to have the greatest potential to produce consistently good performance across laboratories using static-renewal systems. Environ Toxicol Chem 2016;35:2407-2415. (c) 2016 SETAC. PMID- 26823002 TI - Characterization of Actinides Complexed to Nuclear Fuel Constituents Using ESI MS. AB - Electrospray ionization-mass spectrometry (ESI-MS) was tested for its use in monitoring spent nuclear fuel (SNF) constituents including U, Pu, dibutyl phosphate (DBP), and tributyl phosphate (TBP). Both positive and negative ion modes were used to evaluate the speciation of U and Pu with TBP and DBP. Furthermore, apparent stability constants were determined for U complexed to TBP and DBP. In positive ion mode, TBP produced a strong signal with and without complexation to U or Pu, but, in negative ion mode, no TBP, U-TBP, or Pu-TBP complexes were observed. Apparent stability constants were determined for [UO2(NO3)2(TBP)2], [UO2(NO3)2(H2O)(TBP)2], and [UO2(NO3)2(TBP)3]. In contrast DBP, U-DBP, and Pu-DBP complexes were observed in both positive and negative ion modes. Apparent stability constants were determined for the species [UO2(DBP)], [UO2(DBP)3], and [UO2(DBP)4]. Analyzing mixtures of U or Pu with TBP and DBP yielded the formation of ternary complexes whose stoichiometry was directly related to the ratio of TBP to DBP. The ESI-MS protocols used in this study will further demonstrate the utility of ESI-MS and its applicability to process control monitoring in SNF reprocessing facilities. PMID- 26823003 TI - Learning and memory: Coordinating intervals. PMID- 26823004 TI - Synaptic physiology: Seventh sense. PMID- 26823005 TI - Development of a rapid and high-throughput molecular method for detecting the F200Y mutant genotype in benzimidazole-resistant isolates of Fusarium asiaticum. AB - BACKGROUND: The point mutation at codon 200 (TTC->TAC, F200Y) of the beta2 tubulin gene confers resistance to benzimidazole fungicide in Fusarium asiaticum. These isolates with this mutation have been detected mainly by determining the minimum inhibitory concentration (MIC) of fungicides, which is always time consuming, tedious and inefficient. RESULTS: A visual, rapid and efficient method with high specificity was developed, based on loop-mediated isothermal amplification (LAMP). Six sets of LAMP primers were designed, and one set was optimised specifically to distinguish the F200Y mutant genotype. With the optimal LAMP primers, concentrations of LAMP components were optimised. The optimal reaction conditions were 57-64 degrees C for 75 min. The feasibility of the LAMP assay for detection of the F200Y mutant genotype of F. asiaticum was demonstrated by assaying diseased wheat spikelets that were artificially inoculated in the field. CONCLUSION: The new LAMP assay had good specificity, sensitivity, stability and repeatability. It will be useful for assessing the risk of F. asiaticum populations with carbendazim resistance developing in the field, and will also provide important reference data for integrated control of Fusarium head blight caused by F. asiaticum. (c) 2016 Society of Chemical Industry. PMID- 26823006 TI - Characterization of Actin Filament Dynamics during Mitosis in Wheat Protoplasts under UV-B Radiation. AB - Enhanced ultraviolet-B (UV-B) radiation is caused by the thinning ozone and affects photosynthesis and crop yield. Recently, UV-B radiation has been considered as an environmental signal that regulates plant growth. Elucidating the downstream effectors in UV-B-triggered pathways is of particular interest. Previous studies have shown that actin filaments (AFs) play many roles during cell physiological processes. However, the underlying response of AFs to UV-B radiation remains unclear. In this study, wheat protoplasts were isolated from 7 d-old leaves. The dynamics of AFs during mitosis were observed under different treatments. The protoplasts were treated with UV-B radiation, cytochalasin B (CB) and jasplakinolide (JAS). Ph-FITC labelling results revealed typical actin filament structures in the control group; AFs were rearranged under UV-B radiation. AFs polymerized into bundles during interphase, the preprophase band (PPB) structure was destroyed during prophase, and the AFs gathered into plaques during metaphase in response to UV-B radiation. During anaphase and telophase, the distribution of AFs was dispersed. Pharmacologic experiments revealed that CB induced apoptosis and JAS induced nuclear division without cytokinesis in wheat protoplasts. These results indicated that AFs respond to UV-B radiation during mitosis, supplying evidence of UV-B signal transduction in plants. PMID- 26823007 TI - Oxadiazole-Based Cell Permeable Macrocyclic Transition State Inhibitors of Norovirus 3CL Protease. AB - Human noroviruses are the primary causative agents of acute gastroenteritis and a pressing public health burden worldwide. There are currently no vaccines or small molecule therapeutics available for the treatment or prophylaxis of norovirus infections. Norovirus 3CL protease plays a vital role in viral replication by generating structural and nonstructural proteins via the cleavage of the viral polyprotein. Thus, molecules that inhibit the viral protease may have potential therapeutic value. We describe herein the structure-based design, synthesis, and in vitro and cell-based evaluation of the first class of oxadiazole-based, permeable macrocyclic inhibitors of norovirus 3CL protease. PMID- 26823009 TI - Does anxiety-linked attentional bias to threatening information reflect bias in the setting of attentional goals, or bias in the execution of attentional goals? AB - Heightened anxiety vulnerability is characterised by an attentional bias that favours the processing of negative information. However, this anxiety-linked attentional bias is amenable to two quite different explanations. One possibility is that it reflects anxiety-linked bias in the setting of attentional goals that favours setting the goal of attending towards negative information over the alternative goal of attending away from such information. Another possibility is that it reflects anxiety-linked bias in the execution of attentional goals that enhances the execution of the former attentional goal compared to the latter. The present study introduces a novel methodology designed to discriminate the validity of these competing hypotheses, by examining anxiety-linked attentional bias under two conditions. One condition left attentional goals unconstrained. The other condition imposed the attentional goal of either attending towards more negative or more benign emotional stimuli. The finding that anxiety-linked attentional bias was observed only under the former condition supported the hypothesis that anxiety is characterised by a bias favouring the setting attentional goals involving vigilance rather than avoidance of negative information, while giving no support to the hypothesis that anxiety is characterised by a bias reflecting enhanced execution of the former attentional goal compared to the latter. PMID- 26823008 TI - A prospective ascertainment of cancer incidence in sub-Saharan Africa: The case of Kaposi sarcoma. AB - In resource-limited areas, such as sub-Saharan Africa, problems in accurate cancer case ascertainment and enumeration of the at-risk population make it difficult to estimate cancer incidence. We took advantage of a large well enumerated healthcare system to estimate the incidence of Kaposi sarcoma (KS), a cancer which has become prominent in the HIV era and whose incidence may be changing with the rollout of antiretroviral therapy (ART). To achieve this, we evaluated HIV-infected adults receiving care between 2007 and 2012 at any of three medical centers in Kenya and Uganda that participate in the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium. Through IeDEA, clinicians received training in KS recognition and biopsy equipment. We found that the overall prevalence of KS among 102,945 HIV-infected adults upon clinic enrollment was 1.4%; it declined over time at the largest site. Among 140,552 patients followed for 319,632 person-years, the age standardized incidence rate was 334/100,000 person-years (95% CI: 314-354/100,000 person-years). Incidence decreased over time and was lower in women, persons on ART, and those with higher CD4 counts. The incidence rate among patients on ART with a CD4 count >350 cells/mm(3) was 32/100,000 person-years (95% CI: 14 70/100,000 person-years). Despite reductions over time coincident with the expansion of ART, KS incidence among HIV-infected adults in East Africa equals or exceeds the most common cancers in resource-replete settings. In resource-limited settings, strategic efforts to improve cancer diagnosis in combination with already well-enumerated at-risk denominators can make healthcare systems attractive platforms for estimating cancer incidence. PMID- 26823010 TI - Sedentary behavior, gestational diabetes mellitus, and type 2 diabetes risk: where do we stand? AB - A substantial number of pregnancies are complicated by gestational diabetes mellitus (GDM) and up to 70 % of women with GDM go on to develop type 2 diabetes. Given the extensive body of research suggesting physical activity reduces the risk of type 2 diabetes, facilitating physical activity, and reducing sedentary time may be effective approaches to promote the health of women with a previous GDM diagnosis. Here, we discuss physical activity, exercise, and sedentary behavior, in the context of GDM and the potential for type 2 diabetes risk reduction. PMID- 26823011 TI - Band engineering for efficient catalyst-substrate coupling for photoelectrochemical water splitting. AB - To achieve an overall efficient solar water splitting device, not only the efficiencies of photo-converter and catalyst are decisive, but also their appropriate coupling must be considered. In this report we explore the origin of a voltage loss occurring at the interface between a thin film amorphous silicon tandem cell and the TiO2 corrosion protection layer by means of XPS. We find that the overall device can be disassembled into its primary constituents and that they can be analyzed separately, giving insight into the device structure as a whole. Thus, a series of model experiments were conducted, each representing a part of the complete device. We finally arrive at the conclusion, that the formation of a SiO2 interfacial layer between the TiO2 protection layer and the silicon cell gives rise to the voltage loss observed for the whole device. PMID- 26823012 TI - Rab1 recruits WHAMM during membrane remodeling but limits actin nucleation. AB - Small G-proteins are key regulatory molecules that activate the actin nucleation machinery to drive cytoskeletal rearrangements during plasma membrane remodeling. However, the ability of small G-proteins to interact with nucleation factors on internal membranes to control trafficking processes has not been well characterized. Here we investigated roles for members of the Rho, Arf, and Rab G protein families in regulating WASP homologue associated with actin, membranes, and microtubules (WHAMM), an activator of Arp2/3 complex-mediated actin nucleation. We found that Rab1 stimulated the formation and elongation of WHAMM associated membrane tubules in cells. Active Rab1 recruited WHAMM to dynamic tubulovesicular structures in fibroblasts, and an active prenylated version of Rab1 bound directly to an N-terminal domain of WHAMM in vitro. In contrast to other G-protein-nucleation factor interactions, Rab1 binding inhibited WHAMM mediated actin assembly. This ability of Rab1 to regulate WHAMM and the Arp2/3 complex represents a distinct strategy for membrane remodeling in which a Rab G protein recruits the actin nucleation machinery but dampens its activity. PMID- 26823013 TI - Drosophila Nedd4-long reduces Amphiphysin levels in muscles and leads to impaired T-tubule formation. AB - Drosophila Nedd4 (dNedd4) is a HECT ubiquitin ligase with two main splice isoforms: dNedd4-short (dNedd4S) and -long (dNedd4Lo). DNedd4Lo has a unique N terminus containing a Pro-rich region. We previously showed that whereas dNedd4S promotes neuromuscular synaptogenesis, dNedd4Lo inhibits it and impairs larval locomotion. To delineate the cause of the impaired locomotion, we searched for binding partners to the N-terminal unique region of dNedd4Lo in larval lysates using mass spectrometry and identified Amphiphysin (dAmph). dAmph is a postsynaptic protein containing SH3-BAR domains and regulates muscle transverse tubule (T-tubule) formation in flies. We validated the interaction by coimmunoprecipitation and showed direct binding between dAmph-SH3 domain and dNedd4Lo N-terminus. Accordingly, dNedd4Lo was colocalized with dAmph postsynaptically and at muscle T-tubules. Moreover, expression of dNedd4Lo in muscle during embryonic development led to disappearance of dAmph and impaired T tubule formation, phenocopying amph-null mutants. This effect was not seen in muscles expressing dNedd4S or a catalytically-inactive dNedd4Lo(C->A). We propose that dNedd4Lo destabilizes dAmph in muscles, leading to impaired T-tubule formation and muscle function. PMID- 26823014 TI - Stability and flexibility of marginally hydrophobic-segment stalling at the endoplasmic reticulum translocon. AB - Many membrane proteins are integrated into the endoplasmic reticulum membrane through the protein-conducting channel, the translocon. Transmembrane segments with insufficient hydrophobicity for membrane integration are frequently found in multispanning membrane proteins, and such marginally hydrophobic (mH) segments should be accommodated, at least transiently, at the membrane. Here we investigated how mH-segments stall at the membrane and their stability. Our findings show that mH-segments can be retained at the membrane without moving into the lipid phase and that such segments flank Sec61alpha, the core channel of the translocon, in the translational intermediate state. The mH-segments are gradually transferred from the Sec61 channel to the lipid environment in a hydrophobicity-dependent manner, and this lateral movement may be affected by the ribosome. In addition, stalling mH-segments allow for insertion of the following transmembrane segment, forming an Ncytosol/Clumen orientation, suggesting that mH segments can move laterally to accommodate the next transmembrane segment. These findings suggest that mH-segments may be accommodated at the ER membrane with lateral fluctuation between the Sec61 channel and the lipid phase. PMID- 26823015 TI - Regulation of mitochondrial translation of the ATP8/ATP6 mRNA by Smt1p. AB - Expression of the mitochondrially encoded ATP6 and ATP8 genes is translationally regulated by F1 ATPase. We report a translational repressor (Smt1p) of the ATP6/8 mRNA that, when mutated, restores translation of the encoded Atp6p and Atp8p subunits of the ATP synthase. Heterozygous smt1 mutants fail to rescue the translation defect, indicating that the mutations are recessive. Smt1p is an intrinsic inner membrane protein, which, based on its sedimentation, has a native size twice that of the monomer. Affinity purification of tagged Smt1p followed by reverse transcription of the associated RNA and PCR amplification of the resultant cDNA with gene-specific primers demonstrated the presence in mitochondria of Smt1p-ATP8/ATP6 and Smt1p-COB mRNA complexes. These results indicate that Smt1p is likely to be involved in translational regulation of both mRNAs. Applying Occam's principle, we favor a mechanistic model in which translation of the ATP8/ATP6 bicistronic mRNA is coupled to the availability of F1 for subsequent assembly of the Atp6p and Atp8p products into the ATP synthase. The mechanism of this regulatory pathway is proposed to entail a displacement of the repressor from the translationally mute Smt1-ATP8/ATP6 complex by F1, thereby permitting the Atp22p activator to interact with and promote translation of the mRNA. PMID- 26823016 TI - Regulatory roles of conserved phosphorylation sites in the activation T-loop of the MAP kinase ERK1. AB - The catalytic domains of most eukaryotic protein kinases are highly conserved in their primary structures. Their phosphorylation within the well-known activation T-loop, a variable region between protein kinase catalytic subdomains VII and VIII, is a common mechanism for stimulation of their phosphotransferase activities. Extracellular signal-regulated kinase 1 (ERK1), a member of the extensively studied mitogen-activated protein kinase (MAPK) family, serves as a paradigm for regulation of protein kinases in signaling modules. In addition to the well-documented T202 and Y204 stimulatory phosphorylation sites in the activation T-loop of ERK1 and its closest relative, ERK2, three additional flanking phosphosites have been confirmed (T198, T207, and Y210 from ERK1) by high-throughput mass spectrometry. In vitro kinase assays revealed the functional importance of T207 and Y210, but not T198, in negatively regulating ERK1 catalytic activity. The Y210 site could be important for proper conformational arrangement of the active site, and a Y210F mutant could not be recognized by MEK1 for phosphorylation of T202 and Y204 in vitro. Autophosphorylation of T207 reduces the catalytic activity and stability of activated ERK1. We propose that after the activation of ERK1 by MEK1, subsequent slower phosphorylation of the flanking sites results in inhibition of the kinase. Because the T207 and Y210 phosphosites of ERK1 are highly conserved within the eukaryotic protein kinase family, hyperphosphorylation within the kinase activation T-loop may serve as a general mechanism for protein kinase down-regulation after initial activation by their upstream kinases. PMID- 26823017 TI - PtdIns4KIIalpha generates endosomal PtdIns(4)P and is required for receptor sorting at early endosomes. AB - Phosphatidylinositol 4-kinase IIalpha (PtdIns4KIIalpha) localizes to the trans Golgi network and endosomal compartments and has been implicated in the regulation of endosomal traffic, but the roles of both its enzymatic activity and the site of its action have not been elucidated. This study shows that PtdIns4KIIalpha is required for production of endosomal phosphatidylinositol 4 phosphate (PtdIns(4)P) on early endosomes and for the sorting of transferrin and epidermal growth factor receptor into recycling and degradative pathways. Depletion of PtdIns4KIIalpha with small interfering RNA significantly reduced the amount of vesicular PtdIns(4)P on early endosomes but not on Golgi membranes. Cells depleted of PtdIns4KIIalpha had an impaired ability to sort molecules destined for recycling from early endosomes. We further identify the Eps15 homology domain-containing protein 3 (EHD3) as a possible endosomal effector of PtdIns4KIIalpha. Tubular endosomes containing EHD3 were shortened and became more vesicular in PtdIns4KIIalpha-depleted cells. Endosomal PtdIns(4,5)P2 was also significantly reduced in PtdIns4KIIalpha-depleted cells. These results show that PtdIns4KIIalpha regulates receptor sorting at early endosomes through a PtdIns(4)P-dependent pathway and contributes substrate for the synthesis of endosomal PtdIns(4,5)P2. PMID- 26823018 TI - Septin 9 interacts with kinesin KIF17 and interferes with the mechanism of NMDA receptor cargo binding and transport. AB - Intracellular transport involves the regulation of microtubule motor interactions with cargo, but the underlying mechanisms are not well understood. Septins are membrane- and microtubule-binding proteins that assemble into filamentous, scaffold-like structures. Septins are implicated in microtubule-dependent transport, but their roles are unknown. Here we describe a novel interaction between KIF17, a kinesin 2 family motor, and septin 9 (SEPT9). We show that SEPT9 associates directly with the C-terminal tail of KIF17 and interacts preferentially with the extended cargo-binding conformation of KIF17. In developing rat hippocampal neurons, SEPT9 partially colocalizes and comigrates with KIF17. We show that SEPT9 interacts with the KIF17 tail domain that associates with mLin-10/Mint1, a cargo adaptor/scaffold protein, which underlies the mechanism of KIF17 binding to the NMDA receptor subunit 2B (NR2B). Significantly, SEPT9 interferes with binding of the PDZ1 domain of mLin-10/Mint1 to KIF17 and thereby down-regulates NR2B transport into the dendrites of hippocampal neurons. Measurements of KIF17 motility in live neurons show that SEPT9 does not affect the microtubule-dependent motility of KIF17. These results provide the first evidence of an interaction between septins and a nonmitotic kinesin and suggest that SEPT9 modulates the interactions of KIF17 with membrane cargo. PMID- 26823019 TI - Interplay between Solo and keratin filaments is crucial for mechanical force induced stress fiber reinforcement. AB - Mechanical force-induced cytoskeletal reorganization is essential for cell and tissue remodeling and homeostasis; however, the underlying cellular mechanisms remain elusive. Solo (ARHGEF40) is a RhoA-targeting guanine nucleotide exchange factor (GEF) involved in cyclical stretch-induced human endothelial cell reorientation and convergent extension cell movement in zebrafish gastrula. In this study, we show that Solo binds to keratin-8/keratin-18 (K8/K18) intermediate filaments through multiple sites. Solo overexpression promotes the formation of thick actin stress fibers and keratin bundles, whereas knockdown of Solo, expression of a GEF-inactive mutant of Solo, or inhibition of ROCK suppresses stress fiber formation and leads to disorganized keratin networks, indicating that the Solo-RhoA-ROCK pathway serves to precisely organize keratin networks, as well as to promote stress fibers. Of importance, knockdown of Solo or K18 or overexpression of GEF-inactive or deletion mutants of Solo suppresses tensile force-induced stress fiber reinforcement. Furthermore, knockdown of Solo or K18 suppresses tensile force-induced RhoA activation. These results strongly suggest that the interplay between Solo and K8/K18 filaments plays a crucial role in tensile force-induced RhoA activation and consequent actin cytoskeletal reinforcement. PMID- 26823020 TI - Visualization of the Supraglottis in Laryngomalacia With 3-Dimensional Pediatric Endoscopy. AB - IMPORTANCE: The use of 3-dimensional (3D) endoscopy has been described in the pediatric airway and has been shown to improve visualization of complex airway anatomy. Laryngomalacia is one of the most common airway disorders evaluated in pediatric otolaryngology offices. Whether 3D visualization is superior to standard endoscopy as a means for assessment and surgical management of complex airway anatomy is unclear. OBJECTIVE: To describe a pilot case series using 3D endoscopy to facilitate supraglottoplasty and to assess surgical outcomes. DESIGN, SETTING, AND PARTICIPANTS: A prospective case series was conducted of 11 children undergoing supraglottoplasty from July 1, 2010, to June 31, 2014, at a tertiary care pediatric hospital. Infants and children with symptomatic laryngomalacia were eligible for the study. Follow-up was completed on December 31, 2014, and data were assessed from February 1 to 15, 2015. INTERVENTIONS: Supraglottoplasty performed using 3D endoscopy. MAIN OUTCOMES AND MEASURES: The outcome data collected included length of hospital stay and frequency of complications (ie, aspiration, granuloma formation, supraglottic narrowing, revision surgery, tracheostomy, and gastrostomy). RESULTS: Eleven children were treated for laryngomalacia with supraglottoplasty (6 boys and 5 girls; mean [SD] age, 29 [85] months). Four of these children (36%) also had grade I subglottic stenosis. The 3D endoscope was judged by all participating senior surgeons to improve visualization of the supraglottic anatomy and to permit more precise tissue removal. No complications occurred after the surgery. Hospital stay was found to be an unreliable indicator owing to multiple comorbidities in many children. Worsening of aspiration occurred in 1 child (9%) who subsequently required gastrostomy tube placement. This child demonstrated progressive neurologic impairment and had severe hypotonia and developmental delay. Another child with subglottic stenosis and subglottic cysts required a tracheostomy owing to severe rhinovirus tracheitis. The remaining 9 children (82%) had good outcomes, with a mean follow-up of 14.7 (range, 12-24) months. CONCLUSIONS AND RELEVANCE: The anatomy of the supraglottis in laryngomalacia is better visualized using 3D techniques. Use of 3D endoscopy may allow for more precise tissue removal. The outcomes and complication rates are similar to those of standard 2D techniques. This study provides a platform to begin comparative analysis between 3D and standard 2D techniques. PMID- 26823021 TI - T2* relaxation time in the detection and assessment of aggressiveness of peripheral zone cancer in comparison with diffusion-weighted imaging. AB - AIM: To investigate the feasibility of T2* relaxation time for distinguishing benign from malignant regions, as well as tumour aggressiveness, within the peripheral zone (PZ) of the prostate in comparison with diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Fifty-eight patients with prostate cancer underwent 3 T magnetic resonance imaging using multi-echo T2* and DWI (maximum b value, 2000 s/mm(2)). Parametric maps were obtained for apparent diffusion coefficient (ADC) and T2* values. Two radiologists reviewed these maps and measured ADC and T2* values in sextants positive for cancer at biopsy. Data were analysed using mixed-model analysis of variance and receiver operating characteristic curves. RESULTS: Ninety-three sextants exhibited a Gleason score of 6; 59 exhibited a Gleason score of 7 or 8. The T2* value was significantly lower in cancerous sextants than in the benign PZ (48.69+0.60 versus 74.14+0.56, p<0.001), as well as in cancerous sextants with higher rather than lower Gleason scores (43.18+0.89 versus 52.18+0.55, p<0.001). The T2* value showed significantly greater specificity for differentiating cancerous sextants from benign PZ than ADC (93.1% versus 89.7%, p<0.001), with equal sensitivity (82.8% versus 81%, p>0.05). The T2* value exhibited significantly greater sensitivity and specificity for differentiating sextants with low- and high-grade cancer than ADC (79.6% versus 64.5% and 81.4% versus 72.9%, respectively; p<0.05). The T2* value had a significantly greater area under the receiver operating characteristic curve for differentiating sextants with low- and high-grade cancer than ADC (0.77 versus 0.71, p<0.01). CONCLUSION: Preliminary findings suggest that the T2* relaxation time has increased diagnostic value compared with DWI in prostate PZ cancer assessment. PMID- 26823022 TI - Contraction-based uterine artery Doppler velocimetry: novel approach for prediction of preterm birth in women with threatened preterm labor. AB - OBJECTIVE: To evaluate whether uterine artery (UtA) Doppler velocimetry during peak uterine contraction is a useful marker for the prediction of preterm delivery. METHODS: In this prospective cohort study, 172 patients admitted with preterm (24-35 weeks' gestation) uterine contractions were evaluated by UtA Doppler velocimetry during peak uterine contraction and by common obstetric measurements including cervical length. For UtA Doppler velocimetry, flow velocity waveforms during peak uterine contraction (determined visually on tocodynamometry) were recorded during three consecutive heart cycles, and the mean UtA pulsatility index (UtA-PI) was calculated. RESULTS: UtA-PI during the peak of contractions was significantly higher in patients who delivered within 7 days than in those who did not (P < 0.001). On receiver-operating characteristics curve analysis of UtA-PI on contraction, the areas under the curve for prediction of delivery within 48 h, 7 days or 14 days, <= 35 weeks and <= 37 weeks were 0.92, 0.88, 0.81, 0.83 and 0.74, respectively. Multiple regression analysis identified UtA-PI on contraction (P < 0.001) and cervical length (P < 0.001) as predictors of admission-to-delivery interval. The corresponding adjusted odds ratios for delivery within 7 days were 16.5 (95% CI, 5.7-47.2) for UtA-PI on contraction >= 1.32, and 14.7 (95% CI, 5.2-41.8) for cervical length <= 28 mm. CONCLUSION: Use of UtA Doppler velocimetry during peak uterine contraction for patients exhibiting symptoms of preterm labor might be effective for the identification of pregnant women at risk of preterm delivery. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26823024 TI - Diffusion-weighted imaging predicts upgrading of Gleason score in biopsy-proven low grade prostate cancers. AB - OBJECTIVE: To analyse whether diffusion-weighted imaging (DWI) predicts Gleason score (GS) upgrading in biopsy-proven low grade prostate cancer (PCa). PATIENTS AND METHODS: A total of 132 patients who had biopsy-proven low grade (GS < 7) PCa, 3T DWI results, and surgical confirmation were retrospectively included in the study. Clinical variables (prostate-specific antigen, greatest percentage of cancer in a biopsy core and percentage of positive cores) and DWI variables (minimum apparent diffusion coefficient [ADCmin ] and mean ADC [ADCmean ]) were evaluated. ADCmin was measured, by two independent, blinded readers, using a region of interest (ROI) of 5-10 mm2 at the area of lowest ADC value within a cancer, while ADCmean was measured using an ROI covering more than half of a cancer. Logistic regression and receiver-operating characteristic curve analyses were performed. RESULTS: The rate of GS upgrading was 46.1% (61/132). In both univariate and multivariate analyses, ADCmin and ADCmean were persistently significant for predicting GS upgrading (P < 0.05), whereas clinical variables were not (P > 0.05). In both readers' results, the area under the curve (AUC) of ADCmin was significantly greater than that of ADCmean (reader 1: AUC 0.760 vs 0.711; P < 0.001; reader 2: AUC 0.752 vs 0.714; P = 0.003). CONCLUSION: Our results showed that DWI may predict GS upgrading of biopsy-proven low grade PCa. The variable ADCmin in PCa may perform better than ADCmean . PMID- 26823023 TI - Kallikrein-related peptidase 8 is expressed in myocardium and induces cardiac hypertrophy. AB - The tissue kallikrein-related peptidase family (KLK) is a group of trypsin- and chymotrypsin-like serine proteases that share a similar homology to parent tissue kallikrein (KLK1). KLK1 is identified in heart and has anti-hypertrophic effects. However, whether other KLK family members play a role in regulating cardiac function remains unknown. In the present study, we demonstrated for the first time that KLK8 was expressed in myocardium. KLK8 expression was upregulated in left ventricle of cardiac hypertrophy models. Both intra-cardiac adenovirus mediated and transgenic-mediated KLK8 overexpression led to cardiac hypertrophy in vivo. In primary neonatal rat cardiomyocytes, KLK8 knockdown inhibited phenylephrine (PE)-induced cardiomyocyte hypertrophy, whereas KLK8 overexpression promoted cardiomyocyte hypertrophy via a serine protease activity-dependent but kinin receptor-independent pathway. KLK8 overexpression increased epidermal growth factor (EGF) production, which was blocked by the inhibitors of serine protease. EGF receptor (EGFR) antagonist and EGFR knockdown reversed the hypertrophy induced by KLK8 overexpression. KLK8-induced cardiomyocyte hypertrophy was also significantly decreased by blocking the protease-activated receptor 1 (PAR1) or PAR2 pathway. Our data suggest that KLK8 may promote cardiomyocyte hypertrophy through EGF signaling- and PARs-dependent but a kinin receptor-independent pathway. It is implied that different KLK family members can subtly regulate cardiac function and remodeling. PMID- 26823025 TI - Altitude and arteriolar hyalinosis after kidney transplantation. AB - The kidney is very susceptible to hypoxic injury. Calcineurin inhibitors (CNIs) induce vasoconstriction and might reduce renal tissue oxygenation. We aimed to investigate if the synergistic deleterious effects of CNI-treatment and hypoxia of high altitude living might accelerate the development of arteriolar hyalinosis in kidney allografts. We stratified all patients who received a kidney graft from 2000 to 2010 in our centre (n = 477) in three groups according to the residential elevation (below 400, between 400 to 600 and above 600 m above sea level) and we retrospectively re-evaluated all transplant biopsies performed during follow-up, specifically looking at the degree of arteriolar hyalinosis, the hallmark of chronic CNI nephrotoxicity. Living at high altitude was markedly associated with a higher degree of arteriolar hyalinosis (P < 0.001). Haemoglobin levels confirmed the functional relevance of different arterial oxygenation among the groups (P = 0.01). Thus, patients living at high altitude seem to be more susceptible to the development of arteriolar hyalinosis after kidney transplantation. PMID- 26823027 TI - Oxychlorination-Dehydrochlorination Chemistry on Bifunctional Ceria Catalysts for Intensified Vinyl Chloride Production. AB - Ceria catalyzes the one-step production of the vinyl chloride monomer (VCM) from ethylene with a high yield because of its bifunctional character: redox centers oxychlorinate ethylene to ethylene dichloride (EDC), which is subsequently dehydrochlorinated to VCM over strong acid sites generated in situ. Nanocrystalline CeO2 and CeO2-ZrO2 lead to a VCM yield of 25 % in a single pass, outperforming the best reported systems and reaching industrially attractive levels. The use of CeO2 intensifies the current two-step process within PVC production encompassing CuCl2 -catalyzed oxychlorination and thermal cracking. In addition, ceria-based materials offer stability advantages with respect to the archetypical CuCl2 -based catalysts. PMID- 26823028 TI - Tetragomphius melis Infection of the Pancreas in Japanese Badger (Meles meles anakuma). PMID- 26823026 TI - Allosteric Pathways in the PPARgamma-RXRalpha nuclear receptor complex. AB - Understanding the nature of allostery in DNA-nuclear receptor (NR) complexes is of fundamental importance for drug development since NRs regulate the transcription of a myriad of genes in humans and other metazoans. Here, we investigate allostery in the peroxisome proliferator-activated/retinoid X receptor heterodimer. This important NR complex is a target for antidiabetic drugs since it binds to DNA and functions as a transcription factor essential for insulin sensitization and lipid metabolism. We find evidence of interdependent motions of Omega-loops and PPARgamma-DNA binding domain with contacts susceptible to conformational changes and mutations, critical for regulating transcriptional functions in response to sequence-dependent DNA dynamics. Statistical network analysis of the correlated motions, observed in molecular dynamics simulations, shows preferential allosteric pathways with convergence centers comprised of polar amino acid residues. These findings are particularly relevant for the design of allosteric modulators of ligand-dependent transcription factors. PMID- 26823029 TI - Early Stage of Progressive Supranuclear Palsy: A Neuropathological Study of 324 Consecutive Autopsy Cases. AB - Diagnosing clinical progressive supranuclear palsy (PSP) is challenging. We hypothesize that there are more cases of pathological PSP than have been clinically identified, but its diagnosis is challenging because the initial lesions and progression of PSP have not yet been clarified. The purpose of our study was to clarify the incidence of PSP in consecutive autopsy cases and identify pathological characteristics of early PSP. We investigated 324 consecutive autopsy patients from a general geriatric hospital (age, mean+/ SD=82.5+/-8.7 years). Paraffin sections of the midbrain were immunostained with anti 4-repeat tau antibodies (RD4). We selected cases showing RD4-positive neurofibrillary tangles and tufted astrocytes in the midbrain sections. Then, we used anti-phosphorylated tau antibody to immunostain sections from the basal ganglia, subthalamic nucleus, midbrain, pons, medulla, and cerebellum. Of the 324 patients, 35 had RD4-positive structures in the midbrain. From these 35 cases, we excluded those for which autopsies confirmed definite PSP (n=5) and cases of corticobasal degeneration (n=1), Alzheimer's disease (n=11), dementia of grain (n=10), and neurofibrillary tangles predominant forms of senile dementia (n=2), leaving 8 cases. We diagnosed these 8 cases as pure PSP-type tauopathy. Pure PSP type tauopathy was detected in 2.5% of the consecutive autopsy cases, and this incidence was 1.6 times greater than that of neuropathologically definite PSP. This pure PSP-type tauopathy likely indicates preclinical stages of PSP. Furthermore, the novel neuropathological finding, which we term "preclinical PSP," is unique and has not previously been reported. In order to elucidate the causes and pathological mechanisms of PSP, preclinical PSP should be investigated further. PMID- 26823030 TI - Factors Associated with High-sensitivity Cardiac Troponin T in Patients with Type 2 Diabetes Mellitus. AB - BACKGROUND: The blood concentration of high-sensitivity cardiac troponin T (hs cTnT) is an established, useful biomarker for evaluating the pathogenesis of heart failure and predicting cardiovascular events. The aim of this study was to evaluate factors that are potentially associated with elevated blood hs-cTnT in patients with type 2 diabetes mellitus. PATIENTS AND METHODS: Patients with type 2 diabetes mellitus (N=280, 111 men and 169 women; mean +/- SD age: 71+/-9 years) with no history of cardiovascular events were enrolled. Relationships between hs cTnT level and various clinical parameters were examined. RESULTS: Hs-cTnT was detected in 244 (87.1%) patients. There were no significant relationships between hs-cTnT and fasting blood glucose levels or insulin resistance. hs-cTnT was significantly correlated with advanced glycation end-product levels at the skin (r=0.23, p<0.001), blood concentrations of brain natriuretic peptide (r=0.23, p<0.001), reactive oxygen metabolites as markers of oxidative stress (r=0.28, p<0.001), and the augmentation index at the radial artery as marker of arterial reflection (r=0.31, p<0.001). Furthermore, multiple regression analysis revealed that these factors were also selected as independent variables, with hs-cTnT as a subordinate factor. CONCLUSION: These results indicate that novel cardiovascular risk factors including advanced glycation end-products, in vivo oxidative stress, and high arterial reflection are closely associated with high concentrations of blood hs-cTnT in patients with type 2 diabetes mellitus. PMID- 26823031 TI - Ambient Temperature Change Increases in Stroke Onset: Analyses Based on the Japanese Regional Metrological Measurements. AB - BACKGROUND: Relationships between various climate factors and stroke have long been a subject of investigation. The present study investigated in a single medical center the effects of periodic temperature changes on the onset of intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), atherothrombotic infarction (AI), lacunar infarction (LI), cardiogenic embolism (CE), and transient ischemic attack (TIA). METHODS: The subjects were 4,310 patients who had been hospitalized because of hemorrhagic or ischemic stroke from January 2000 through December 2005. Ambient temperature data were collected from the Japan Meteorological Agency Database. The following factors were analyzed: number of stroke onsets per day; mean, maximum, and minimum ambient temperatures; and differences between the mean temperatures on the onset day and the previous week. Relationships between temperature factors and totals based on stroke subtypes were assessed by means of regression analyses with a standard least squares model controlling for specific covariates. RESULTS: The daily admissions for ICH, SAH, AI, LI, and CE increased when the mean temperature on the onset day was 1 degrees C lower than that of the previous week. Decreases in minimum ambient temperature predicted increased numbers of admissions for ICH and for SAH. Conversely, a 1 degrees C increase in maximum ambient temperature significantly affected ICH, AI, and CE admissions. There was no definitive relationship between temperature change and admissions for TIA. CONCLUSION: Both absolute and comparative changes in ambient temperature are related to increased onsets of hemorrhagic and ischemic stroke in Japan. PMID- 26823032 TI - Proximal Entrapment Neuropathy of the Median Nerve above the Elbow-Case Report. AB - We report an extremely rare case of proximal entrapment neuropathy of the median nerve above the elbow in a 44-year-old man who presented with paresthesia with median nerve distribution. Tinel's sign was located in the upper arm medial to the biceps and 5 cm proximal to the elbow. The patient underwent microsurgery under local anesthesia. The fascia covering the brachial- and the biceps brachii muscle entrapped median nerve. After operation, he reported symptom improvement. Lesions above the elbow should be considered as possible causative factors of entrapment neuropathy of the median nerve. PMID- 26823033 TI - Successful Treatment of Necrotizing Fasciitis after Rectal Surgery with the Application of a Negative-pressure Wound Therapy: A Case Study. AB - INTRODUCTION: Necrotizing fasciitis (NF) is an aggressive soft tissue infection that involves the deep fascia and is characterized by the extensive deterioration of the surrounding tissue. Immediate recognition and aggressive treatment, including debridement and systemic antibiotics, are mandatory for the successful management of NF. Following radical debridement, closure of the remaining wound can pose significant reconstructive challenges. Accumulating evidence indicates that application of negative-pressure wound therapy (NPWT) is useful in the treatment of patients with severe acute complex wounds, including NF. CASE PRESENTATION: A 58-year-old man who had undergone surgical resection for rectal carcinoma followed by chemo-radiation therapy developed NF of the pelvis and thigh three years after the surgical procedure. Following extensive debridement, a VAC system was applied to the large open wound and successfully contributed to wound bed cleansing, which was followed by surgery for skin grafting. CONCLUSION: This case demonstrates the successful management of a complex and potentially lethal wound of the perineum to lower leg with debridement and skin grafting as well as with the application of the VAC system. PMID- 26823034 TI - Gymnastic Formation-related Injury to Children in Physical Education. AB - OBJECTIVE: Current data indicate that the rate of trauma in children during gymnastic formation is increasing, especially while creating a structure with a certain height, such as the human pyramid. The goal of the present study was to clarify the clinical characteristics of these injuries. METHODS: In this single institution review, all children treated for a gymnastic formation-related injury at Nippon Medical School Hospital from 2013 through 2015 were identified through the institution's registry. The injury mechanism was classified, and injury severity, interventions, and outcome were examined. RESULTS: Eight children were treated for a gymnastic formation-related injury. They were 7 boys and 1 girl aged 10 to 15 years (mean age, 13.1+/-1.8 years). Neurotrauma ranging from concussion to spinal cord injury without radiographic abnormality occurred in 6 patients (75%). No intracranial hemorrhagic lesions were detected. The Glasgow Coma Scale score on arrival was 15 in all 8 patients, and neurological deficits were present in 1 patient. No patient required surgical intervention. All patients made a full recovery after discharge from the hospital. No patients died. The average follow-up period was 2.1+/-0.9 weeks. CONCLUSIONS: Neurotrauma is a frequent result of gymnastic formation accidents in children. Healthcare workers and teachers should recognize this type of injury, and public education that targets parents should be introduced. PMID- 26823035 TI - Recurrent Gallstone Ileus Successfully Treated with Conservative Therapy. AB - Gallstone ileus is a rare complication of cholecystolithiasis, with the majority of cases requiring surgical treatment. In this paper, we describe a case of gallstone ileus that was successfully treated twice with conservative therapy. An 85-year-old woman was admitted to our hospital because of abdominal pain and vomiting. She had previously been treated with antibiotics for cholecystitis arising from 2 gallbladder stones. Computed tomography (CT) revealed that the small bowel was dilated and that 1 of the gallbladder stones had disappeared. In addition, a 28*22-mm calcified mass was found in the small-bowel lumen. We diagnosed gallstone ileus and performed nasogastric drainage for decompression. Follow-up CT revealed migration of the impacted stone, and symptoms had improved. However, 2 months after discharge, the patient's symptoms recurred. A CT scan revealed that the small bowel was again dilated and that the remaining gallstone had disappeared from the gallbladder. A 28*25-mm calcified mass was found in the small-bowel lumen. We diagnosed recurrent gallstone ileus. Because the gallstone was almost the same size as the previous one, we selected the same conservative decompression treatment. Fourteen days after the patient was admitted, the stone was evacuated with the feces. Although many cases of gallstone ileus require surgical treatment, spontaneous passage was achieved in this case. When treatment is chosen for gallstone ileus, the patient's presentation and clinical course must be considered. PMID- 26823036 TI - Laparoscopic Diagnosis for Spermatic Cord Metastasis from Esophageal Squamous Cell Carcinoma: Report of a Case. AB - We report a case of previously unreported metastasis to the spermatic cord from esophageal squamous cell carcinoma. A 63-year-old Japanese man underwent laparoscopy-assisted esophageal bypass surgery for an advanced esophageal cancer. An elastic hard tumor was found in the right lateral inguinal fossa on intraoperative laparoscopy, and laparoscopic enucleation was performed. Histological examination of the resected tumor revealed a moderately differentiated squamous cell carcinoma, compatible with metastasis from the esophageal cancer. Two months after the operation, computed tomography revealed a heterogeneously enhanced groin mass (20 mm in diameter) involving the right spermatic cord. To our knowledge, this is the first reported case of a solitary metastasis to the spermatic cord from esophageal squamous cell carcinoma. PMID- 26823037 TI - Effects of Fluoxetine on Neural Functional Prognosis after Ischemic Stroke: A Randomized Controlled Study in China. AB - OBJECTIVE: We investigated the effects of fluoxetine on the short-term and long term neural functional prognoses after ischemic stroke. METHODS: In this prospective randomized controlled single-blind clinical study in China, eligible patients afflicted with ischemic stroke were randomized into control and treatment groups. Patients in the treatment group received fluoxetine in addition to the basic therapies in the control group over a period of 90 days. The follow up period was 180 days. We evaluated the effects of fluoxetine on the National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) score after ischemic stroke through single- and multiple-factor analysis. RESULTS: The mean NIHSS score on day 180 after treatment was significantly lower in the treatment group than in the control group (P = .009). The mean BI scores on days 90 and 180 were significantly higher in the treatment group (P = .026) than in the control group (P = .011). The improvements in the NIHSS and BI scores on days 90 and 180 compared with baseline in the treatment group were all significantly greater than that in the control group (P = .033, P = .013, P = .013, P = .019, respectively). Treatment with fluoxetine was an independent factor affecting the NIHSS and BI scores on day 180 after treatment. CONCLUSION: Treatment with fluoxetine for 90 days after ischemic stroke can improve the long-term neural functional outcomes. PMID- 26823038 TI - Distorted body representations in healthy cognition. AB - Delusions and misperceptions about the body are a conspicuous feature of numerous neurological and psychiatric conditions. In stark contrast to such pathological cases, the immediacy and familiarity of our ordinary experience of our body can make it seem as if our representation of our body is highly accurate, even infallible. Recent research has begun to demonstrate, however, that large and systematic distortions of body representation are a normal part of healthy cognition. Here, I describe this research, focusing on distortions of body representations underlying tactile distance perception and position sense. I also discuss evidence for distortions of higher-order body representations, such as the conscious body image. Finally, I will end with a discussion of the potential relations among different body representations and their distortions. PMID- 26823039 TI - The efficacy of tyrosine kinase inhibitor dasatinib on colonic mucosal damage in murine model of colitis. AB - BACKGROUND AND OBJECTIVE: Ulcerative colitis is an inflammatory condition of the colon in the gastrointestinal system. Currently, the most potent medications used for ulcerative colitis produce no response in 20-30% of cases. There is a need for more efficient and reliable medications. Tyrosine kinase inhibitors have shown efficacy in some inflammatory diseases. Although dasatinib, a tyrosine kinase inhibitor, suppresses proinflammatory cytokines in colonic tissue, there are a few cases of hemorrhagic colitis with dasatinib. There is no study investigating the effect of dasatinib on experimental colitis. We aimed to investigate the effect of dasatinib in a colitis model induced with acetic acid in our study. METHODS: In the study, 24 male Sprague-Dawley rats randomly distributed into 4 groups of 6 rats each as control, dasatinib, colitis and dasatinib+colitis groups. For colitis induction, 4% acetic acid was used. Sacrificing of the rats was performed on the seventh day. Disease activity, morphologic and histological injury, superoxide dismutase, myeloperoxidase and malondialdehyde activity, TNFalpha and CD3 expression were assessed in colonic tissue. RESULTS: Apart from malondialdehyde, significant difference in all parameters between the control and colitis groups was determined. Difference between the colitis and colitis+dasatinib groups was not significant in only weight loss and biochemical parameters. Though dasatinib does not fully resolve the changes in colitis, there was significant regression. CONCLUSIONS: Dasatinib decreased the inflammation in a rodent model of colitis. It may be provide this effect by the suppression of TNFalpha. Dasatinib may be one of the treatment options for ulcerative colitis. PMID- 26823040 TI - An observational and comparative study on intraductal papillary mucinous neoplasm of the biliary tract and the pancreas from a Chinese cohort. AB - BACKGROUND: Intraductal papillary mucinous neoplasms of the biliary tract (BT IPMNs) are unique but very rare biliary tumors. The relationship between BT-IPMNs and intraductal papillary mucinous neoplasm of the pancreas (P-IPMNs) was still unclear and controversial. OBJECTIVE: We aimed to evaluate the clinical, radiological, histopathological, and prognostic characteristics of BT-IPMNs and P IPMNs to achieve a better understanding of these two rare bilio-pancreatic diseases and their connections. METHODS: Data of a total of 116 patients who were all surgically treated and histopathologically diagnosed as BT-IPMNs or P-IPMNs from January 2004 to December 2014 in our single institution was all retrospectively collected and analyzed. RESULTS: This study respectively enrolled 32 patients with BT-IPMNs and 84 ones with P-IPMNs. The differences between BT IPMNs and P-IPMNs in age, sex ratios, clinical presentation, elevated tumor markers and proportion of malignancy were not statistically significant (P>0.05), while the tumor diameter of BT-IPMNs was notably smaller than P-IPMNs (1.72cm, 4.56cm, respectively; P=0.028). Patients with BT-IPMNs were more likely manifest the symptoms of cholangitis, compared to those with P-IPMNs who showed pancreatitis (75%, 30%, respectively; P=0.039). Bile duct dilatation (100%), tumor of bile duct cavity (50%) or/and cystic dilatation of the bile duct (50%) were the typical manifestations of preoperative imaging examinations of BT-IPMNs, in which tumors were mainly located in intrahepatic or hepatic hilar region (26, 81%). Surgery has been the curable treatment for BT-IPMNs in which left hepatic lobectomy was the most commonly performed procedure (20, 63%). Finally, compared with P-IPMNs, the overall mean survival time of patients with BT-IPMNs was a little shorter (59.1mon, 86.7mon, respectively; P=0.002). CONCLUSION: BT-IPMNs are a sort of rare and separate biliary tract neoplasm, which might be related with the stones of biliary tract or the infections of parasite. Although arising in different organs and representing different features, BT-IPMNs and P-IPMNs shared considerable clinical and pathological similarities which might represent related or similar development process in the bilio-pancreatic duct systems. PMID- 26823041 TI - The pathophysiology of intrahepatic cholestasis of pregnancy. AB - A number of liver disorders are specific to pregnancy. Amongst these, intrahepatic cholestasis of pregnancy (ICP), also known as obstetric cholestasis (OC), is the commonest, affecting approximately 1 in 140 UK pregnancies. Patients commonly present in the third trimester with severe pruritus and deranged serum liver tests; bile acids are elevated, in severe cases >40 MUmol/L. Although the disease is considered relatively benign for the mother, increased rates of adverse fetal outcomes, including stillbirth, are associated with ICP. As our knowledge of the mechanisms underlying bile acid homeostasis has advanced in the last 15 years our understanding of ICP has grown, in particular with respect to genetic influences on susceptibility to the disease, the role of reproductive hormones and their metabolites and the possible identity of the pruritic agents. In this review, we will describe recent advances in the understanding of this condition with a particular emphasis on how aspects of genetic and reproductive hormone involvement in pathophysiology have been elucidated. We also review recent developments regarding our knowledge of placental and fetal pathophysiology and the long-term health consequences for the mother and child. PMID- 26823042 TI - Alterations in serum levels of fetuin A and selenoprotein P in chronic hepatitis C patients with concomitant type 2 diabetes: A case-control study. AB - BACKGROUND: Insulin resistance (IR) and type 2 diabetes mellitus (T2DM) are serious extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. However, the mechanism underlying the IR in chronic HCV is obscure. Hepatokines are group of liver-derived protein, which affect the glucose and lipid metabolism in several tissues. Fetuin A (also known as human alpha2-HS-glycoprotein) is one of the hepatokines, which was recognized as a natural inhibitor of the insulin receptor tyrosine kinase in liver and skeletal muscle. Additionally, selenoprotein P has emerged as an important hepatokine, which primarily acts as selenium transporter and has been reported to be implicated in glucose homeostasis in human. OBJECTIVE: The aim of the current case-control study was to investigate the serum levels of both fetuin A and selenoprotein P in chronic hepatitis C patients with or without T2DM and to correlate their levels with other biochemical parameters of insulin resistance. MAIN FINDINGS: Our results showed that, serum fetuin A levels increased significantly in HCV patients compared with controls (P<0.01) and surplus increase was found in HCV with concomitant T2DM (P>0.001). However, selenoprotein P levels significantly elevated only in patients with both HCV and T2DM (P<0.05) compared with the healthy subjects. Both fetuin A and selenoprotein P were positively correlated with fasting blood glucose. Yet, only fetuin A was significantly correlated to the HOMA-IR (r=0.28; P=0.03). CONCLUSIONS: These results indicate crucial roles played by fetuin A and selenoprotein P in the IR caused by HCV and that both hepatokines may be targets for the development of therapies to treat or inhibit insulin resistance associated to HCV. However, further studies on large scale should be conducted to confirm our findings. PMID- 26823043 TI - Hepatocellular carcinoma diagnosis: Circulating microRNAs emerge as robust biomarkers. PMID- 26823044 TI - Prognostic factors for survival after hepatic resection of early hepatocellular carcinoma in HBV-related cirrhotic patients. AB - OBJECTIVE: The study aimed to identify clinico-pathologic factors that predict survival in early hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV)-related cirrhosis undergoing liver resection. METHODS: A population-based cohort was investigated to identify cirrhotic patients with confirmed early HCC (tumor size<=5cm and absence of nodal involvement, metastases, or major vascular invasion) after hepatic resection at the Eastern Hepatobiliary Surgery Hospital (Shanghai, China) from April 2005 and November 2010 using the Surveillance, Epidemiology, and End Results (SEER) database. These patients were studied retrospectively in terms of their clinical characteristics and prognostic factors. Predictors for survival were evaluated using Kaplan-Meier methods and Cox proportional hazards models. Besides, a simple prognostic scoring system was proposed to stratify these patients. RESULTS: Of 537 (2.6% of all HCC patients in this period) cirrhotic patients with early HCC identified who had underwent liver resection, 87% were male. Median tumor size was 2.9cm, and 67% of patients had tumors>2cm. Following hepatic resection, overall median and 5-year survival were 75 months and 58%, respectively. Tumor size>2cm (hazard ratio [HR]=1.56), multifocality (HR=1.34), non-anatomic resection (HR=1.44) and vascular invasion (HR=2.03) were associated with worse prognosis (P<0.05). Moreover, these patients could be further stratified into 4 distinct prognostic groups based on the prognostic scoring system developed. CONCLUSION: Tumor size>2cm, multifocality, non-anatomic resection and vascular invasion may be used to stratify HBV-related cirrhotic patients with early HCC after resection. Besides, these data also indicate that pathologic staging is important even in small HCC. PMID- 26823045 TI - Stimulant use for ADHD and relative age in class among children in Israel. AB - BACKGROUND: Diagnosis of children with attention-deficit/hyperactivity disorder (ADHD) is increasing. The present study sought to identify characteristics and medication treatment patterns of children with ADHD and compare them by relative age in class, sex, ethnicity, family size, sibling order, and other socioeconomic status, as well as find trends in disparity of pharmacotherapy. METHODS: This study was based on data from 1 013 149 Clalit Health Services members aged 6-17 years during 2006-2011. Centrally acting sympathomimetic drug purchases were compared according to children's estimated relative age in class; youngest third (born August to November), middle third (born April to July), and oldest third (born December to March). Treatment trends were determined and compared according to sociodemographic and family-related factors. RESULTS: The overall prevalence of stimulant use in the population was 2.6% in 2006 and 4.9% in 2011. The annual incidence of stimulant use increased from 0.75% to 1.36%, rising more sharply among children in the older age groups (>=12) than among younger ones. Moreover, the youngest third of children in class was more likely to use medication than the oldest third (risk ratio (RR) 1.17, confidence interval (CI) 1.12-1.23) or the middle third (RR 1.06, CI 1.01-1.11). Of the different ethnic sectors, incidence of stimulant use was highest among general Jewish (1.8% in 2011) and lowest among Arabs (0.37% in 2011). CONCLUSIONS: The use of stimulant medication is growing among children in Israel. Although the overall use does not exceed the estimated prevalence of ADHD among children, the appropriateness of prescribing to the Israeli pediatric population, especially to the youngest children in class, may be questionable. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26823046 TI - Ending childhood obesity: a time for action. PMID- 26823047 TI - Erratum: Gut Microbiota Alterations can predict Hospitalizations in Cirrhosis Independent of Diabetes Mellitus. PMID- 26823048 TI - Metatropic dysplasia is associated with increased fracture risk. PMID- 26823049 TI - The 'community' in community case management of childhood illnesses in Malawi. AB - BACKGROUND: Malawi has achieved a remarkable feat in reducing its under-5 mortality in time to meet its MDG 4 target despite high levels of poverty, low female literacy rates, recurrent economic crises, a severe shortage of human resources for health, and poor health infrastructure. The country's community based delivery platform (largely headed by Health Surveillance Assistants, or HSAs) has been well established since the 1960s, although their tasks and responsibilities have evolved from surveillance to health promotion and prevention, and more recently to include curative services. However, the role of and the form that community involvement takes in community-based service delivery in Malawi is unclear. DESIGN: A qualitative rapid appraisal approach was utilised to explore the role of community involvement in the HSA programme in Malawi to better understand how the various community providers intersect to support the delivery of integrated community case management by HSAs. Twelve focus group discussions and 10 individual interviews were conducted with HSAs, HSA supervisors, mothers, members of village health committees (VHCs), senior Ministry of Health officials, district health teams, and implementing partners. RESULTS: Our findings reveal that HSAs are often deployed to areas outside of their village of residence as communities are not involved in selecting their own HSAs in Malawi. Despite this lack of involvement in selection, the high acceptance of the HSAs by community members and community accountability structures such as VHCs provide the programme with legitimacy and credibility. CONCLUSIONS: This study provides insight into how community involvement plays out in the context of a government-managed professionalised community service delivery platform. It points to the need for further research to look at the impact of removing the role of HSA selection and deployment from the community and placing it at the central level. PMID- 26823051 TI - New Methods for the Analysis of Fat-Soluble Vitamins in Infant Formula and Adult Nutritionals. AB - The AOAC Stakeholder Panel on Infant Formula and Adult Nutritionals (SPIFAN) defined fat-soluble vitamins (FSVs) to include vitamins A, D, E, and K. The levels of FSVs have been closely scrutinized because of a number of factors, including nutrition value especially in foods used to provide sole-source nutrition and the potential for health risks associated with content both below and above recommended levels. Stricter scrutiny and emphasis on nutrient-level compliance with regulatory requirements placed an increased demand on analytical methods that were fit-for-purpose, provided accurate and precise results. Over time, compendial methods have been developed and published by organizations such as AOAC INTERNATIONAL, the European Committee for Standardization, the International Dairy Federation, and the International Organization for Standardization, among others. In general, these methods have shown adequate precision for regulatory compliance based on example food matrixes for which they were designed. However, method evaluation for infant formulas and adult nutritional products was limited to very few matrixes within these categories. As such, method applicability gaps were noted and correlated with more complicated or diverse product matrixes. AOAC undertook the task of modernizing test methods for the determination of nutrients in infant formulas and in adult nutritional products formulated specifically for both healthy adults and those requiring specific nutritional intake. Composition of products in this category continued to evolve, which in turn presented increasing and new challenges to analytical methodology. A summary of a new generation of candidate compendial methods for determination of FSVs in these matrixes, identified by SPIFAN, is presented here. PMID- 26823050 TI - Using mixed methods to evaluate perceived quality of care in southern Tanzania. AB - OBJECTIVE: To compare perceived quality of maternal and newborn care using quantitative and qualitative methods. DESIGN: A continuous household survey (April 2011 to November 2013) and in-depth interviews and birth narratives. SETTING: Tandahimba district, Tanzania. PARTICIPANTS: Women aged 13-49 years who had a birth in the previous 2 years were interviewed in a household survey. Recently delivered mothers and their partners participated in in-depth interviews and birth narratives. INTERVENTION: None. MAIN OUTCOME MEASURES: Perceived quality of care. RESULTS: Quantitative: 1138 women were surveyed and 93% were confident in staff availability and 61% felt that required drugs and equipment would be available. Drinking water was easily accessed by only 60% of respondents using hospitals. Measures of interaction with staff were very positive, but only 51% reported being given time to ask questions. Unexpected out-of-pocket payments were higher in hospitals (49%) and health centres (53%) than in dispensaries (31%). Qualitative data echoed the lack of confidence in facility readiness, out of-pocket payments and difficulty accessing water, but was divergent in responses about interactions with health staff. More than half described staff interactions that were disrespectful, not polite, or not helpful. CONCLUSION: Both methods produced broadly aligned results on perceived readiness, but divergent results on perceptions about client-staff interactions. Benefits and limitations to both quantitative and qualitative approaches were observed. Using mixed methodologies may prove particularly valuable in capturing the user experience of maternal and newborn health services, where they appear to be little used together. PMID- 26823052 TI - The modeling of medical expenditure data from a longitudinal survey using the generalized method of moments (GMM) approach. AB - Medical expenditure data analysis has recently become an important problem in biostatistics. These data typically have a number of features making their analysis rather difficult. Commonly, they are heavily right-skewed, contain a large percentage of zeros, and often exhibit large numbers of missing observations because of death and/or the lack of follow-up. They are also commonly obtained from records that are linked to large longitudinal data surveys. In this manuscript, we suggest a novel approach to modeling these data through the use of generalized method of moments estimation procedure combined with appropriate weights that account for both dropout due to death and the probability of being sampled from among the National Long Term Care Survey (NLTCS) subjects. This approach seems particularly appropriate because of the large number of subjects relative to the length of observation period (in months). We also use a simulation study to compare our proposed approach with and without the use of weights. The proposed model is applied to medical expenditure data obtained from the 2004-2005 NLTCS-linked Medicare database. The results suggest that the amount of medical expenditures incurred is strongly associated with higher number of activities of daily living (ADL) disabilities and self reports of unmet need for help with ADL disabilities. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26823053 TI - Gastric bypass significantly improves quality of life in morbidly obese patients with type 2 diabetes. AB - OBJECTIVE: To evaluate the impact of Roux-en-Y gastric bypass (RYGB) on quality of life in obese diabetic patients compared to standard medical therapy for type 2 diabetes mellitus. METHODS: We prospectively studied two matched obese populations with type 2 diabetes. Thirty patients underwent laparoscopic RYGB and 31 received standard medical therapy combined with a diabetes support and education program (DSE), consisting of educational sessions on diet and exercise. Groups were matched by age, gender, weight, glucostatic parameters, and use of glucose-lowering medications (oral agents and insulin therapy). Health-related quality of life (HRQOL) was assessed using the normalized SF-36 questionnaire, and data were collected at baseline and at 12-month follow-up. RESULTS: Diabetic patients who underwent RYGB experienced a statistically significant increase in their overall HRQOL. However, the role-physical and mental health domains increased but did not reach statistical significance. Diabetic patients in the medical therapy and DSE group did not show any significant increase in HRQOL. The between-group differences for the HRQOL changes from baseline were significant, other than for role-physical and mental health domains. Percentage changes in glucostatic parameters, discontinuation of glucose-lowering medications, and T2DM remission were not found to predict the percentage change in SF-36 scores at 12 months after RYGB. CONCLUSIONS: For the first time, with a prospective matched control study, we demonstrate a significant improvement in HRQOL in obese diabetic patients who underwent RYGB, but not in those who were offered standard medical therapy and DSE. PMID- 26823054 TI - True NOTES TME resection with splenic flexure release, high ligation of IMA, and side-to-end hand-sewn coloanal anastomosis. AB - INTRODUCTION: Natural orifice transluminal endoscopic surgery (NOTES) represents the ultimate expression of minimally invasive surgery. We have developed and present here an initial feasibility and safety study of transanal total mesorectal excision (TME) with splenic flexure release, high ligation of the IMA and IMV, and side-to-end coloanal anastomosis with temporary diverting ileostomy for rectal cancer. METHODS: A program of full NOTES TME resection with release of the splenic flexure, high ligation of the IMA/IMV, with side-to-end coloanal anastomosis was performed transanally from December 2013 to July 2014. Demographics, preoperative, perioperative, and postoperative data were prospectively obtained. Operative components were broken into TME, colonic mobilization, splenic flexure release, IMA/IMV transection, transanal extraction of specimen, and coloanal anastomosis for analysis of performance completion. RESULTS: There were 3 women and 1 man on whom we operated. Mean age was 56 (46 65). Mean BMI was 26 (23.8-30.2). The operation was completed entirely transanally in 2 patients. Transanal component completion of the operation was as follows: TME in 3/4; colonic mobilization in 4/4; splenic flexure release in 3/4; IMA/IMV transection in 3/4; transanal specimen extraction in 4/4; coloanal anastomosis in 4/4. Abdominal time for completion of component parts was: splenic flexure release 4:53 (min:s), IMA/IMV 19:43, completion of TME 13:41. Mean EBL was 194 cc (25-500). Aside from stoma site, there were no abdominal incisions. There were no mortalities. Mesorectum was intact in all 4 patients and with negative circumferential and distal margins. CONCLUSION: This experience supports the feasibility and safety of a true NOTES TME. The critical anatomic views demonstrated on video affirm the potential of this approach for distal rectal cancer. Colorectal surgery represents the most logical application for NOTES. While highly promising, a great deal of work remains to develop the technique and applicability of NOTES colorectal surgery. PMID- 26823055 TI - Long-term outcomes of patients with common bile duct injury following laparoscopic cholecystectomy. AB - INTRODUCTION: Common bile duct (CBD) injury is a serious and dreaded complication of cholecystectomy. A paucity of data assessing long-term outcomes exists. This study aimed to determine long-term mortality and liver transplantation rates following CBD injury requiring operative intervention. METHODS: Patients were identified via the New York State (NYS) Planning and Research Cooperative System longitudinal administrative database which captures patient-level data from every inpatient and outpatient hospital discharge in NYS. In total, 125 patients with CBD injuries were identified following 156,958 laparoscopic cholecystectomies for cholelithiasis performed in NYS from 2005 to 2010. Patients were then tracked by unique identifier to obtain rate of liver transplantation. Follow-up ranged from 4 to 9 years from surgery. RESULTS: There were 125 patients with CBD injuries detected. No mortalities occurred within 30 days. All-cause mortality was 20.8 % (n = 26) with mean time to death 1.64 +/- 1.08 years. One patient who underwent hepaticoenterostomy required a liver transplant 4.3 years after surgery. Significant factors predictive of all-cause mortality included: age >61, Medicare insurance, male gender, White race, diabetes, hypertension and pulmonary complications following surgery. Overall 30-day morbidity, timing to and type of operative intervention did not influence mortality. CONCLUSION: Considerable long term mortality, 20.8 %, is associated with common bile duct injury requiring operative intervention. This was an increase of 8.8 % above the cohort's expected age-adjusted rate of death. The mortality rate is appreciably higher than quoted previously. No difference was demonstrated by type of repair required. Liver transplant rate was 0.8 %. These data have significant implications for patient and family counseling both prior to cholecystectomy and following CBD injury. PMID- 26823056 TI - Feasibility of laparoscopic liver resection for caudate lobe: technical strategy and comparative analysis with anteroinferior and posterosuperior segments. AB - BACKGROUND: Although laparoscopic liver resection (LLR) is now considered a standard procedure in peripheral segments, there are few reports on laparoscopic segment 1 (Sg1) resection. The aim of this study was to assess both safety and feasibility of Sg1 LLR. METHODS: From 2000 to 2014, all patients who underwent LLR were identified from a prospective database. Patients with resection of Sg1 (Sg1 group) were compared with those with resection of anteroinferior segments (AI group: segments 3, 4b, 5, 6) or posterosuperior segments (PS group: segments 4a, 7, 8), in terms of tumor characteristics, surgical treatment, and short-term outcomes. RESULTS: There were 15, 151, and 67 patients in Sg1, AI, and PS groups. Tumor size and tumor number were similar between the three groups (p = 0.139, p = 0.102). Operative time was significantly shorter in Sg1 (150 min) and AI group (135 min) compared with PS group (180 min) (p = 0.021). Median blood loss was notably higher in PS group (140 ml) compared with Sg1 group (75 ml) and AI group (10 ml) (p = 0.001). No mortality was observed in all groups. Postoperative complication rate was 20.0 % with Sg1 group, 14.6 % with AI group, and 20.9 % with PS group (p = 0.060). The rate of major complication was significantly higher in Sg1 group (13.3 %) and PS group (11.9 %) compared with AI group (4.0 %) (p = 0.042). Resection margins were clear in all Sg1 and PS group patients, whereas two (1.3 %) patients in AI group had R1 margins (p = 0.586). CONCLUSION: The laparoscopic approach of isolated resection located in the caudate lobe is a feasible and curative surgical option in selected patients. PMID- 26823057 TI - Laparoscopic-assisted ERCP and EUS in patients with prior Roux-en-Y gastric bypass surgery: a dual-center case series experience. AB - BACKGROUND: Patients with Roux-en-Y gastric bypass (RYGB) develop pancreatobiliary issues after surgery. Endoscopic management via the conventional route with endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) is quite limited due to the altered anatomy. Laparoscopic assisted ERCP (LA-ERCP) via the excluded stomach has been highly successful. Reported use of laparoscopic-assisted EUS (LA-EUS) is extremely rare. METHODS: A retrospective review was conducted at two tertiary referral centers for cases that involved laparoscopic-assisted ERCP and EUS. Patient demographic data were collected along with data regarding procedure, indication, complications and length of stay. RESULTS: A total of 16 cases involving 15 patients were identified: 11 cases of LA-ERCP and five cases of combined LA-EUS plus LA-ERCP were performed. Four patients had previously undergone failed endoscopy via the conventional route (27 %). There was a 100 % biliary/pancreatic cannulation and intervention rate. There were no endoscopic-related complications. Therapeutic interventions included laparoscopic cholecystectomy, lysis of adhesions, biliary and pancreatic sphincterotomy, biliary and pancreatic stent placement, stone removal including mechanical lithotripsy and EUS biopsy and diagnosis of pancreatic cancer. Average discharge was on postoperative day 3.4. However, 50 % were discharged after 1 day. CONCLUSIONS: LA-ERCP and combined LA-EUS plus LA ERCP are safe and highly successful diagnostic and therapeutic modalities for a wide variety of pancreatobiliary ailments in RYGB patients. PMID- 26823058 TI - Body composition changes after totally laparoscopic distal gastrectomy with delta shaped anastomosis: a comparison with conventional Billroth I anastomosis. AB - BACKGROUND: The purpose of this study was to compare body composition changes of patients undergoing totally laparoscopic distal gastrectomy (TLDG) with delta shaped anastomosis (DSA) versus conventional laparoscopic distal gastrectomy (CLDG). METHODS: Data from gastric cancer patients who underwent laparoscopic distal gastrectomy for histologically proven gastric cancer in KNUMC from January 2013 to May 2014 were collected and reviewed. We examined 85 consecutive patients undergoing TLDG or CLDG: 41 patients underwent TLDG and 44 patients underwent CLDG. Body composition was assessed by segmental multifrequency bioelectrical impedance analysis. We compared the changes in nutritional parameters and body composition from preoperative status between the two groups at postoperative 6 and 12 months. RESULTS: All of the postoperative changes in the body composition and nutritional indices were similar between the two groups with the exception of visceral fat areas (VFAs) and albumin levels. VFAs increased at 6 months postoperatively in the TLDG group and a significant difference was shown at 12 months postoperatively between the TLDG and CLDG groups (86.7 +/- 22.8 and 74.7 +/- 21.9 cm(2), respectively, P < 0.05). Postoperative albumin levels were higher in the TLDG group with statistical significance at 6 and 12 months after surgery (6 months, P = 0.028; 12 months, P = 0.012). CONCLUSIONS: The influence of TLDG with DSA on nutrition and body composition seemed comparable to those of CLDG. Six months postoperatively, VFAs and albumin levels were recovered in the TLDG group but not in the CLDG group. Thus, TLDG seems to be a novel surgical method. PMID- 26823059 TI - Task performance in standard laparoscopy in comparison with single-incision laparoscopy in a modified skills trainer. AB - BACKGROUND: Single-incision laparoscopy (SIL) is similar to conventional laparoscopic surgery (LAP), but carries specific technical challenges due to lack of triangulation, reduced dexterity, conflicts due to inline instrumentation, and impaired visualization. This study was designed to evaluate technical skill performance of SIL versus LAP surgery in a simulated environment. METHODS: We developed a modified laparoscopic skills trainer for SIL based upon the fundamentals of laparoscopic surgery (FLS) model. This includes a standard laparoscopic tower for visualization, allowing replication of the conflicts between scope and instruments. It also has a modified trainer box allowing use of different access devices and instruments for SIL. Sixteen subjects at different levels of training (novice through expert) completed four FLS tasks with standard LAP techniques. They then practiced the same tasks using SIL technique until they reached a steady state of performance. The first and last SIL trials were recorded. RESULTS: Baseline SIL peg transfer was worse than FLS (254 +/- 157 s vs 99 +/- 27, p < 0.0002). Final SIL time was still significantly worse than FLS (173 +/- 130, p < 0.02). FLS, baseline SIL, and final SIL circle cutting were not significantly different (p = 0.058). Final SIL loop ligation was significantly faster than FLS (48 +/- 19 vs 70 +/- 42, p < 0.05). FLS suturing was faster than SIL suturing (281 +/- 188 vs. 526 +/- 105, p < 0.01). There was substantial dropout due to frustration with SIL, and only two surgeons were able to successfully complete SIL suturing. CONCLUSIONS: There are technical challenges with SIL that vary depending on task. Peg transfer and suturing were significantly impaired in SIL, while circle cutting was not significantly affected, and ligating loop was faster with SIL than LAP. These challenges may impact clinical outcomes of SIL and should influence training in SIL as well as future product development. PMID- 26823061 TI - 3D Dewetting for Crystal Patterning: Toward Regular Single-Crystalline Belt Arrays and Their Functionality. AB - Arrays of unidirectional dewetting behaviors can be generated by using 3D wettability-difference micropillars, yielding highly ordered organic single crystalline belt arrays. These patterned organic belts show an improved mobility record and can be used as flexible pressure sensors with high sensitivity. PMID- 26823060 TI - Feasibility of endoscopic submucosal dissection for upper gastrointestinal submucosal tumors treatment and value of endoscopic ultrasonography in pre operation assess and post-operation follow-up: a prospective study of 224 cases in a single medical center. AB - BACKGROUND AND AIMS: Diagram, diagnosis, and treatment with endoscopic submucosal dissection (ESD) for upper gastrointestinal submucosal tumors (SMTs) remain controversial, although endoscopic ultrasonography (EUS) and ESD have been established in diagnosis and treatment of SMTs in decades, respectively. In this study, we have investigated prospectively the profile of upper gastrointestinal SMTs, assessed the effect and feasibility of ESD in upper gastrointestinal SMTs treatment, as well as value of EUS in pre-ESD diagnosis and post-ESD follow-up for gastrointestinal SMTs. METHODS: The upper gastrointestinal SMTs patients detected with endoscopy were further checked by EUS, then received series ESD treatment, and fulfilled 3- and 12-month follow-up EUS detection between July 2011 and March 2015. The parameters of SMTs with EUS examination (size, original layer) and treatment with ESD (en bloc resection rate, procedure time, procedure related complications) were investigated and analyzed. RESULTS: A total number of 224 patients with upper gastrointestinal SMTs were enrolled, and 108 (48.2 %) were men. The mean age was 50.4 +/- 12.0 years (range 19-77 years). In total, 92 (41.1 %), 14 (6.3 %), 61 (27.2 %), 22 (9.8 %), 25 (11.2 %), and 10 (4.5 %) SMTs were located in esophagus, cardiac, fundus, body and antrum of stomach, duodenum, respectively. Two hundred and eight (92.9 %) patients were successfully treated with an en bloc ESD, while other 16 patients (7.1 %) suffered ESD failure (5.3 %, 12 case) or severe complications (1.8 %, 4 cases). The mean procedure time of ESD was 47.4 +/- 27.3 min (range 10-180 min). The mean size of the SMTs measured with ESD samples was 13.6 +/- 9.5 mm (range 4-113 mm). In total, 87 (38.8 %), 23 (10.3 %), and 114 (50.9 %) tumors originated from muscularis mucosa, submucosa, and muscularis propria, respectively. The majority of SMTs were leiomyoma (109, 48.7 %) and gastrointestinal stromal tumors (GIST) (77, 34.4 %), while other SMTs were confirmed as ectopic pancreas (21, 9.4 %), adenoid tumor (8, 3.6 %), lipoma (5, 2.2 %), neuroendocrine tumor (3, 1.3 %), and granulosa cell tumor (1, 0.4 %). The accuracy rate of EUS in pathological diagnosis or original layer was 82.6 % (185/224) or 74.6 % (167/224). Residual tumors were detected with EUS in 3 patients (1.3 %) in 3-month follow-up and no recurrence during 12-month follow-up period. CONCLUSIONS: The predominant SMTs in upper gastrointestinal tract were leiomyoma in esophageal tumors which originated from muscularis mucosae and GIST in stomach which originated from muscularis propria detected satisfactorily with EUS. This study showed that ESD was a safe and effective treatment for upper gastrointestinal SMTs. PMID- 26823062 TI - Assessment of imidacloprid-induced mutagenic effects in somatic cells of Swiss albino male mice. AB - Pesticides are being used for plant protection to increase food protection and to reduce insect-borne diseases worldwide. Exposure to the pesticides may cause genotoxic effects on both the target and nontarget organisms, including man. Therefore, the mutagenicity evaluation of such pesticides has become a priority area of research. Imidacloprid (IMI), a neonicotinoid insecticide, is widely used in agriculture either alone or in combination with other insecticides. A combined approach employing micronucleus test (MNT) and chromosomal aberrations assay (CA) was utilized to assess the mutagenicity of imidacloprid in bone marrow of Swiss albino male mice. IMI suspension was prepared in 3% gum acacia and administered at doses of 5.5, 11 and 22 mg/kg body weight for 7, 14 and 28 days to mice. IMI treatment resulted in a dose and time-dependant increase in the frequencies of micronuclei per cell and chromosomal aberrations in bone marrow cells. A statistically significant increase in chromosomal aberrations and micronuclei/cell was found only after daily treatment of IMI at highest selected dose (22 mg/kg body weight) for longest selected time period (28 days) compared to the control group. Thus, daily exposure of imidacloprid at a dose level of 22 mg/kg body weight for 28 days caused mutagenic effects on the somatic cells of Swiss albino male mice. PMID- 26823064 TI - Anatomy of Good Prenatal Care: Perspectives of Low Income African-American Women on Barriers and Facilitators to Prenatal Care. AB - BACKGROUND: Although early, consistent prenatal care (PNC) can be helpful in improving poor birth outcomes, rates of PNC use tend to be lower among African American women compared to Whites. This study examines low-income African American women's perspectives on barriers and facilitators to receiving PNC in an urban setting. METHODS: We conducted six focus groups with 29 women and individual structured interviews with two women. Transcripts were coded to identify barriers and facilitators to obtaining PNC; codes were reviewed to identify emergent themes. RESULTS: Barriers to obtaining PNC included structural barriers such as transportation and insurance, negative attitudes towards PNC, perceived poor quality of care, unintended pregnancy, and psychosocial stressors such as overall life stress and chaos. Facilitators of PNC included positive experiences such as trusting relationships with providers, respectful staff and providers, and social support. CONCLUSIONS: Findings suggest important components in an ideal PNC model to engage low-income African-American women. PMID- 26823063 TI - Incarcerated Black Women in the Southern USA: A Narrative Review of STI and HIV Risk and Implications for Future Public Health Research, Practice, and Policy. AB - Incarcerated black women in the southern USA are understudied despite the high prevalence of sexually transmitted infections (STI) and human immunodeficiency virus (HIV). These incarceration and health disparities are rooted in centuries of historically inequitable treatment. Amidst the current dialogue on mass incarceration in the south and its relationship to the health of the black community, individual and environmental risk factors for STI/HIV transmission are seldom paired with discussions of evidence-based solutions. A narrative review of the literature from January 1995 to May 2015 was conducted. This sample of the literature (n = 18) revealed that partner concurrency, inconsistent condom use, sex work, previous STI, and drug abuse augmented individual STI/HIV risk. Recommended interventions include those which promote healthier relationships, cultural competence, and gender specificity, as well as those that enhance prevention skills. Policy recommendations include improving cultural sensitivity, cultural competence, and cultural humility training for clinicians, as well as substantially increasing funding for prevention, treatment, and rehabilitative services. These recommendations are timely given the recent national attention to incarceration, STI, and HIV disparities, particularly in the southern USA. PMID- 26823065 TI - Racial Differences in Posttraumatic Stress Disorder Vulnerability Following Hurricane Katrina Among a Sample of Adult Cigarette Smokers from New Orleans. AB - Although blacks are more likely than whites to experience posttraumatic stress disorder (PTSD) after a natural disaster, the reasons for this disparity are unclear. This study explores whether race is associated with PTSD after adjusting for differences in preexisting vulnerabilities, exposure to stressors, and loss of social support due to Hurricane Katrina using a representative sample of 279 black and white adult current and past smokers who were present when Hurricane Katrina struck, and identified it as the most traumatic event in their lifetime. Multiple logistic regression models evaluated whether differential vulnerability (pre-hurricane physical and mental health functioning, and education level), differential exposure to hurricane-related stressors, and loss of social support deterioration reduced the association of race with PTSD. Blacks were more likely than whites to screen positive for PTSD (49 vs. 39 %, respectively, p = 0.030). Although blacks reported greater pre-hurricane vulnerability (worse mental health functioning and lower educational attainment) and hurricane-related stressor exposure and had less social support after the hurricane, only pre-hurricane mental health functioning attenuated the association of race with screening positive for PTSD. Thus, racial differences in pre-hurricane functioning, particularly poorer mental health, may partially explain racial disparities in PTSD after natural disasters, such as Hurricane Katrina. Future studies should examine these associations prospectively using representative cohorts of black and whites and include measures of residential segregation and discrimination, which may further our understanding of racial disparities in PTSD after a natural disaster. PMID- 26823067 TI - In vivo oxidative stress alters thiol redox status of peroxiredoxin 1 and 6 and impairs rat sperm quality. AB - Oxidative stress, the imbalance between the production of reactive oxygen species (ROS) and antioxidant activity is a major culprit of male infertility. Peroxiredoxins (PRDXs) are major antioxidant enzymes of mammalian spermatozoa and are thiol oxidized and inactivated by ROS in a dose-dependent manner. Their deficiency and/or inactivation have been associated with men infertility. The aim of this study was to elucidate the impact of oxidative stress, generated by the in vivo tert-butyl hydroperoxide (tert-BHP) treatment on rat epididymal spermatozoa during their maturation process. Adult Sprague-Dawley males were treated with 300 MUmoles tert-BHP/kg or saline (control) per day intraperitoneal for 15 days. Lipid peroxidation (2-thibarbituric acid reactive substances assay), total amount and thiol oxidation of PRDXs along with the total amount of superoxide dismutase (SOD), motility and DNA oxidation (8-hydroxy-deoxyguanosine) were determined in epididymal spermatozoa. Total amount of PRDXs and catalase and thiol oxidation of PRDXs were determined in caput and cauda epididymis. While animals were not affected by treatment, their epididymal spermatozoa have decreased motility, increased levels of DNA oxidation and lipid peroxidation along with increased PRDXs (and not SOD) amounts. Moreover, sperm PRDXs were highly thiol oxidized. There was a differential regulation in the expression of PRDX1 and PRDX6 in the epididymis that suggests a segment-specific role for PRDXs. In conclusion, PRDXs are increased in epididymal spermatozoa in an attempt to fight against the oxidative stress generated by tert-BHP in the epididymis. These findings highlight the role of PRDXs in the protection of sperm function and DNA integrity during epididymal maturation. PMID- 26823068 TI - Rare primary seminal vesicle cystadenoma: computed tomography and magnetic resonance imaging findings. PMID- 26823066 TI - Residual Effects of Restless Sleep over Depressive Symptoms on Chronic Medical Conditions: Race by Gender Differences. AB - BACKGROUND: Sleep and depression are comorbid problems that contribute to the development of chronic medical conditions (CMC) over time. Although racial and gender differences in the bidirectional associations between sleep, depression, and CMC are known, very limited information exists on heterogeneity of the residual effects of sleep problems over depressive symptoms on CMC across race by gender groups. AIM: Using a life-course perspective, the present study compared race by gender groups for residual effects of restless sleep over depressive symptoms on CMC. METHODS: We used data from waves 1 (year 1986), 4 (year 2001), and 5 (year 2011) of the Americans' Changing Lives Study (ACL). The study followed 294 White men, 108 Black men, 490 White women, and 237 Black women for 25 years. Restless sleep, depressive symptoms (Center for Epidemiological Studies Depression scale [CES-D]), and number of chronic medical conditions (hypertension, diabetes, chronic lung disease, heart disease, stroke, cancer, and arthritis) were measured in 1986, 2001, and 2011. We employed multi-group cross lagged modeling, with chronic medical conditions as the outcome and race by gender as the groups. RESULTS: Major group differences were found in the residual effect of restless sleep on CMC over depressive symptoms across race by gender groups. Restless sleep in 2001 predicted CMC 10 years later in 2011 among Black women (standardized adjusted B = .135, P < .05) and White men (standardized adjusted = .145, P < .01) and White women (standardized adjusted B = .171, P < .001) but not Black men (standardized adjusted B = .001, P > .05). CONCLUSION: Race by gender heterogeneity in the residual effect of restless sleep over depressive symptoms on CMC over 25 years suggests that comorbid poor sleep and depressive symptoms differently contribute to development of multi-morbidity among subpopulations based on the intersection of race and gender. Thus, interventions that try to prevent comorbid sleep problems and depression as a strategy to prevent medical conditions may benefit from tailoring based on the intersection of race and gender. PMID- 26823069 TI - Benign prostatic hyperplasia and lower urinary tract symptoms. A review of current evidence. AB - CONTEXT: The treatment of benign prostatic hyperplasia (BPH) is changing due to a greater understanding of the disease and the development of the functional concept of lower urinary tract symptoms (LUTS). OBJECTIVES: To describe the current state of BPH and the diagnosis and treatment of LUTS. ACQUISITION OF EVIDENCE: We summarise the issues presented and debated by a group of expert urologists during the First UROVI Congress, sponsored by the Spanish Urological Association. SUMMARY OF THE EVIDENCE: LUTS encompasses filling, voiding and postvoiding symptoms that affect patients' quality of life. The aetiological diagnosis is an important element in starting the most ideal treatment. For this reason, new alternative therapies (both pharmacological and surgical) are needed to help individually address the symptoms in the various patient profiles. There is now a new combination of drugs (6mg of solifenacin and 0.4mg of the tamsulosin oral controlled absorption system) for treating moderate to severe filling symptoms and emptying symptoms associated with BPH in patients who do not respond to monotherapy. Furthermore, new surgical techniques that are increasingly less invasive help provide surgical options for older patients and those with high comorbidity. CONCLUSIONS: The availability of drugs that can act on the various LUTS helps integrate the pathophysiological paradigm into the functional one, providing more appropriate treatment for our patients. PMID- 26823070 TI - Cynicism and other attitudes towards patients in an emergency department in a middle eastern tertiary care center. AB - BACKGROUND: A caring, compassionate practitioner of the medical arts is the idealized version of what makes a good doctor. If asked to think of a painting of a doctor we most likely conjure an image of a physician sitting at a patient's bedside checking the pulse with a concerned look on his face. The reality is however that cynicism, among other negative attitudes, is becoming more prominent among physicians and medical staff. The causes and extent of cynicism likely vary among medical departments and different cultures. In this study, we aimed to assess attitudes of medical students and physicians in an Emergency Department (ED) in Lebanon that accommodates both local patients and is also known to attract patients from around the Middle East. METHODS: A total of 30 students, residents and attending physicians at the American University of Beirut Medical Center were invited to participate. All participants underwent semi-structured interviews that were recorded, transcribed and then analyzed for common themes. RESULTS: More negative emotions were expressed among participants than positive ones. Negative emotions were more frequently expressed among medical students, interns and residents than attending physicians. Cynicism in the ED was commonly reported however, maintenance of professionalism and adequate patient care were underscored. While empathy was recurrently found among participants, a trend towards a decrease in empathy with career progression was noted among attending physicians. Further, negative feelings towards patient families were prominent. Participants tended to categorize patients based on willingness to cooperate, gender, age, case acuity, ethnic origins and social status. CONCLUSIONS: Cynicism emerged as a prominent theme among medical students and staff in our study. However, participants were also empathetic. These attitudes were generally attributed to the peculiar stressors associated with the Lebanese culture, low acuity cases and "VIP" patients. It is crucial to explore methods in order to decrease cynicism and improve patient care. Also, the implications of these attitudes on patient care remain to be discovered. PMID- 26823071 TI - Static Mechanical Loading Influences the Expression of Extracellular Matrix and Cell Adhesion Proteins in Vaginal Cells Derived From Premenopausal Women With Severe Pelvic Organ Prolapse. AB - INTRODUCTION: Primary human vaginal cells derived from women with severe pelvic organ prolapse (POP-HVCs) demonstrate altered cellular characteristics as compared to cells derived from asymptomatic women (control-HVCs). Using computer controllable Flexcell stretch unit, we examined whether POP-HVCs react differently to mechanical loading as compared to control-HVCs by the expression of extracellular matrix (ECM) components, cell-ECM adhesion proteins, and ECM degrading and maturating enzymes. METHODS: Vaginal tissue biopsies from premenopausal patients with Pelvic Organ Prolapse Quantification System stage >=3 (n = 8) and asymptomatic controls (n = 7) were collected during vaginal hysterectomy or repair. Human vaginal cells were isolated by enzymatic digestion, seeded on collagen (COLI)-coated plates, and stretched (24 hours, 25% elongation). Total RNA was extracted, and 84 genes were screened using Human ECM and Adhesion Molecules polymerase chain reaction array; selected genes were verified by quantitative reverse transcription-polymerase chain reaction. Stretch conditioned media (SCM) were collected and analyzed by protein array, immunoblotting, and zymography. RESULTS: In mechanically stretched control-HVCs, transcript levels of integrins (ITGA1, ITGA4, ITGAV, and ITGB1) and matrix metalloproteinases (MMPs) 2, 8, and 13 were downregulated (P < .05); in POP-HVCs, MMP1, MMP3, and MMP10, ADAMTS8 and 13, tissue inhibitor of metalloproteinases (TIMPs) 1 to 3, ITGA2, ITGA4, ITGA6, ITGB1, contactin (CNTN1), catenins (A1 and B1), and laminins (A3 and C1) were significantly upregulated, whereas COLs (1, 4, 5, 6, 11, and 12) and LOXL1 were downregulated. Human vaginal cells massively secrete MMPs and TIMPs proteins; MMP1, MMP8, MMP9 protein expression and MMP2 gelatinase activity were increased, whereas TIMP2 decreased in SCM from POP-HVCs compared to control-HVCs. CONCLUSIONS: Primary human vaginal cells derived from women with severe pelvic organ prolapse and control-HVCs react differentially to in vitro mechanical stretch. Risk factors that induce stretch may alter ECM composition and cell-ECM interaction in pelvic floor tissue leading to the abatement of pelvic organ support and subsequent POP development. PMID- 26823072 TI - Soluble carbohydrate content variation in Sanionia uncinata and Polytrichastrum alpinum, two Antarctic mosses with contrasting desiccation capacities. AB - BACKGROUND: Cryptogamic vegetation dominates the ice-free areas along the Antarctic Peninsula. The two mosses Sanionia uncinata and Polytrichastrum alpinum inhabit soils with contrasting water availability. Sanionia uncinata grows in soil with continuous water supply, while P. alpinum grows in sandy, non-flooded soils. Desiccation and rehydration experiments were carried out to test for differences in the rate of water loss and uptake, with non-structural carbohydrates analysed to test their role in these processes. RESULTS: Individual plants of S. uncinata lost water 60 % faster than P. alpinum; however, clumps of S. uncinata took longer to dry than those of P. alpinum (11 vs. 5 h, respectively). In contrast, rehydration took less than 10 min for both mosses. Total non-structural carbohydrate content was higher in P. alpinum than in S. uncinata, but sugar levels changed more in P. alpinum during desiccation and rehydration (60-50 %) when compared to S. uncinata. We report the presence of galactinol (a precursor of the raffinose family) for the first time in P. alpinum. Galactinol was present at higher amounts than all other non-structural sugars. CONCLUSIONS: Individual plants of S. uncinata were not able to retain water for long periods but by growing and forming carpets, this species can retain water the longest. In contrast individual P. alpinum plants required more time to lose water than S. uncinata, but as moss cushions they suffered desiccation faster than the later. On the other hand, both species rehydrated very quickly. We found that when both mosses lost 50 % of their water, carbohydrates content remained stable and the plants did not accumulate non structural carbohydrates during the desiccation prosses as usually occurs in vascular plants. The raffinose family oligosaccarides decreased during desiccation, and increased during rehydration, suggesting they function as osmoprotectors. PMID- 26823073 TI - The rationale for targeting TGF-beta in chronic liver diseases. AB - BACKGROUND: Transforming growth factor (TGF)-beta is a pluripotent cytokine that displays several tissue-specific biological activities. In the liver, TGF-beta is considered a fundamental molecule, controlling organ size and growth by limiting hepatocyte proliferation. It is involved in fibrogenesis and, therefore, in worsening liver damage, as well as in triggering the development of hepatocellular carcinoma (HCC). TGF-beta is known to act as an oncosuppressor and also as a tumour promoter in HCC, but its role is still unclear. DESIGN: In this review, we discuss the potential role of TGF-beta in regulating the tumoural progression of HCC, and therefore the rationale for targeting this molecule in patients with HCC. RESULTS: A considerable amount of experimental preclinical evidence suggests that TGF-beta is a promising druggable target in patients with HCC. To support this hypothesis, a phase II clinical trial is currently ongoing using a TGF-beta pathway inhibitor, and results will soon be available. CONCLUSIONS: The identification of new TGF-beta related biomarkers will help to select those patients most likely to benefit from therapy aimed at inhibiting the TGF-beta pathway. New formulations that may provide a more controlled and sustained delivery of the drug will improve the therapeutic success of such treatments. PMID- 26823074 TI - Silver-Mediated Intermolecular 1,2-Alkylarylation of Styrenes with alpha-Carbonyl Alkyl Bromides and Indoles. AB - A new iron-facilitated silver-mediated radical 1,2-alkylarylation of styrenes with alpha-carbonyl alkyl bromides and indoles is described, and two new C-C bonds were generated in a single step through a sequence of intermolecular C(sp(3)-Br functionalization and C(sp(2))-H functionalization across the alkenes. This method provides an efficient access to alkylated indoles with broad substrate scope and excellent selectivity. PMID- 26823075 TI - Multifocal musculoskeletal tuberculosis mimicking multiple bone metastases: a case report. AB - BACKGROUND: The occurrence of non-contiguous, multiple, and remote involvement tuberculous spondylitis is rare. The clinical presentation in patients with multifocal musculoskeletal tuberculosis may closely mimic that in patients with multiple bone metastases, which makes the accurate clinical diagnosis challenging. Herein, we report a multifocal musculoskeletal tuberculosis case that was misdiagnosed for 8 months as multiple bone metastases. CASE PRESENTATION: A 63-year-old male farmer of Chinese Han ethnicity presented to us with pain in left side of the neck, right side of the chest and the back for 10 months without typical tuberculosis symptoms. His past medical history, the CT and fluoroscopy-guided biopsy were negative for tuberculosis. Interferon gamma by T-SPOT was also negative. Radiological findings including CT, MRI and PET-CT suggested that the patient had multiple metastases. Accordingly, the patient was misdiagnosed as having musculoskeletal tumors until a swelling under the right nipple ulcerated. The smear test for acid-fast bacilli and the PCR test for TB DNA of the pus from the swollen area were both positive, leading to the final correct diagnosis of musculoskeletal tuberculosis. CONCLUSION: The proper diagnosis of musculoskeletal tuberculosis is clinically challenging due to Mycobacterium tuberculosis variants involved and atypical presentations, especially when the lesions are multiple. Our findings indicate that multiple tuberculous spondylitis must be considered in the differential diagnosis of multiple musculoskeletal lesions. PMID- 26823076 TI - Sleep and Behavioral Problems in Children with Autism Spectrum Disorder. AB - Children with autism spectrum disorder (ASD) are at high risk for sleep disturbance and behavioral dysregulation. However, the relationships between these difficulties are not fully understood. The current study examined the relationships between specific types of sleep and behavioral problems among 81 children with ASD. Sleep problems were significantly associated with physical aggression, irritability, inattention, and hyperactivity. In multivariate analyses, distinct sets of sleep problems accounted for between 22 and 32 % of the variance in behavior problems across models. These results indicate that sleep disturbance is associated with behavioral dysregulation among children with ASD. Of note, night awakenings had the most consistently strong association with daytime behavior problems, even after controlling for the effects of age and sex. PMID- 26823077 TI - Why increasing availability of ART is not enough: a rapid, community-based study on how HIV-related stigma impacts engagement to care in rural South Africa. AB - BACKGROUND: Stigma is a known barrier to HIV testing and care. Because access to antiretroviral therapy reduces overt illness and mortality, some scholars theorized that HIV-related stigma would decrease as treatment availability increased. However, the association between ART accessibility and stigma has not been as straightforward as originally predicted. METHODS: We conducted a "situational analysis"--a rapid, community-based qualitative assessment to inform a combination HIV prevention program in high prevalence communities. In the context of this community-based research, we conducted semi-structured interviews and focus groups with 684 individuals in four low-resource sub-districts in North West Province, South Africa. In addition to using this data to inform programming, we examined the impact of stigma on the uptake of services. RESULTS: Findings suggested that anticipated stigma remains a barrier to care. Although participants reported less enacted stigma, or hostility toward people living with HIV, they also felt that HIV remains synonymous with promiscuity and infidelity. Participants described community members taking steps to avoid being identified as HIV-positive, including avoiding healthcare facilities entirely, using traditional healers, or paying for private doctors. Such behaviors led to delays in testing and accessing care, and problems adhering to medications, especially for men and youth with no other health condition that could plausibly account for their utilization of medical services. CONCLUSIONS: We conclude that providing access to ART alone will not end HIV-related stigma. Instead, individuals will remain hesitant to seek care as long as they fear that doing so will lead to prejudice and discrimination. It is critical to combat this trend by increasing cultural acceptance of being seropositive, integrating HIV care into general primary care and normalizing men and youths' accessing health care. PMID- 26823078 TI - Prioritization of anti-malarial hits from nature: chemo-informatic profiling of natural products with in vitro antiplasmodial activities and currently registered anti-malarial drugs. AB - BACKGROUND: A large number of natural products have shown in vitro antiplasmodial activities. Early identification and prioritization of these natural products with potential for novel mechanism of action, desirable pharmacokinetics and likelihood for development into drugs is advantageous. Chemo-informatic profiling of these natural products were conducted and compared to currently registered anti-malarial drugs (CRAD). METHODS: Natural products with in vitro antiplasmodial activities (NAA) were compiled from various sources. These natural products were sub-divided into four groups based on inhibitory concentration (IC50). Key molecular descriptors and physicochemical properties were computed for these compounds and analysis of variance used to assess statistical significance amongst the sets of compounds. Molecular similarity analysis, estimation of drug-likeness, in silico pharmacokinetic profiling, and exploration of structure-activity landscape were also carried out on these sets of compounds. RESULTS: A total of 1040 natural products were selected and a total of 13 molecular descriptors were analysed. Significant differences were observed among the sub-groups of NAA and CRAD for at least 11 of the molecular descriptors, including number of hydrogen bond donors and acceptors, molecular weight, polar and hydrophobic surface areas, chiral centres, oxygen and nitrogen atoms, and shape index. The remaining molecular descriptors, including clogP, number of rotatable bonds and number of aromatic rings, did not show any significant difference when comparing the two compound sets. Molecular similarity and chemical space analysis identified natural products that were structurally diverse from CRAD. Prediction of the pharmacokinetic properties and drug-likeness of these natural products identified over 50% with desirable drug-like properties. Nearly 70% of all natural products were identified as potentially promiscuous compounds. Structure-activity landscape analysis highlighted compound pairs that form 'activity cliffs'. In all, prioritization strategies for the NAA were proposed. CONCLUSIONS: Chemo-informatic profiling of NAA and CRAD have produced a wealth of information that may guide decisions and facilitate anti malarial drug development from natural products. Articulation of the information provided within an interactive data-mining environment led to a prioritized list of NAA. PMID- 26823079 TI - On the control mechanisms of the nitrite level in Escherichia coli cells: the mathematical model. AB - BACKGROUND: Due to a high toxicity of nitrite and its metabolites, it is of high interest to study mechanisms underlying the low NO2 level maintenance in the cell. During anaerobic growth of Escherichia coli the main nitrite-reducing enzymes are NrfA and NirB nitrite reductases. NrfA reductase is localized in the cell periplasm and uses NO2 as an electron acceptor to create a proton gradient; NirB reductase is restricted to the cytoplasm and metabolizes excessive nitrite inside the cell, the uptake of which is mediated by the transporter protein NirC. While it is known that these three systems, periplasmic, cytoplasmic and transport, determine nitrite uptake and assimilation in the cell as well as its excretion, little is known about their co-ordination. RESULTS: Using a mathematical model describing the nitrite utilization in E. coli cells cultured in a flow chemostat, the role of enzymes involved in nitrite metabolism and transport in controlling nitrite intracellular levels was investigated. It was demonstrated that the model adapted to the experimental data on expression of nrfA and nirB genes encoding NrfA and NirB nitrite reductases, can describe nitrite accumulation kinetics in the chemostat in the millimolar range of added substrate concentrations without any additional assumptions. According to the model, in this range, low intracellular nitrite level, weakly dependent on its concentration in the growth media, is maintained (mcM). It is not sufficient to consider molecular-genetic mechanisms of NrfA reductase activity regulation to describe the nitrite accumulation dynamics in the chemostat in the micromolar range (<=1 mM) of added nitrite concentrations. Analysis of different hypotheses has shown that the mechanism of local enzyme concentration change due to membrane potential-induced diffusion from the cytoplasm to the periplasm at low nitrite levels is sufficient to explain the nitrite accumulation dynamics in the chemostat. CONCLUSIONS: At nitrite concentrations in the media more than 2 mM, the model adapted to the experimental data on nitrite utilization dynamics in E. coli cells cultured in the flow chemostat demonstrates the largest contribution of genetic mechanisms involved in nrf and nir operons activity regulation to the control of nitrite intracellular levels. The model predicts a significant contribution of the membrane potential to the periplasmic NrfA nitrite reductase activity regulation and nitrite utilization dynamics at substrate concentrations <=1 mM. PMID- 26823080 TI - Impacts of extreme heat on emergency medical service calls in King County, Washington, 2007-2012: relative risk and time series analyses of basic and advanced life support. AB - BACKGROUND: Exposure to excessive heat kills more people than any other weather related phenomenon, aggravates chronic diseases, and causes direct heat illness. Strong associations between extreme heat and health have been identified through increased mortality and hospitalizations and there is growing evidence demonstrating increased emergency department visits and demand for emergency medical services (EMS). The purpose of this study is to build on an existing regional assessment of mortality and hospitalizations by analyzing EMS demand associated with extreme heat, using calls as a health metric, in King County, Washington (WA), for a 6-year period. METHODS: Relative-risk and time series analyses were used to characterize the association between heat and EMS calls for May 1 through September 30 of each year for 2007-2012. Two EMS categories, basic life support (BLS) and advanced life support (ALS), were analyzed for the effects of heat on health outcomes and transportation volume, stratified by age. Extreme heat was model-derived as the 95th (29.7 degrees C) and 99th (36.7 degrees C) percentile of average county-wide maximum daily humidex for BLS and ALS calls respectively. RESULTS: Relative-risk analyses revealed an 8 % (95 % CI: 6-9 %) increase in BLS calls, and a 14 % (95 % CI: 9-20 %) increase in ALS calls, on a heat day (29.7 and 36.7 degrees C humidex, respectively) versus a non-heat day for all ages, all causes. Time series analyses found a 6.6 % increase in BLS calls, and a 3.8 % increase in ALS calls, per unit-humidex increase above the optimum threshold, 40.7 and 39.7 degrees C humidex respectively. Increases in "no" and "any" transportation were found in both relative risk and time series analyses. Analysis by age category identified significant results for all age groups, with the 15-44 and 45-64 year old age groups showing some of the highest and most frequent increases across health conditions. Multiple specific health conditions were associated with increased risk of an EMS call including abdominal/genito-urinary, alcohol/drug, anaphylaxis/allergy, cardiovascular, metabolic/endocrine, diabetes, neurological, heat illness and dehydration, and psychological conditions. CONCLUSIONS: Extreme heat increases the risk of EMS calls in King County, WA, with effects demonstrated in relatively younger populations and more health conditions than those identified in previous analyses. PMID- 26823081 TI - Statin use associated with a reduced risk of pneumonia requiring hospitalization in patients with myocardial infarction: a nested case-control study. AB - BACKGROUND: Statins have been reported to prevent adverse cardiovascular events in patients with myocardial infarction (MI). However, the association of statin use and the risk of pneumonia requiring hospitalization in MI patients remains unclear. METHODS: A nested case-control study was conducted by using data from the National Health Insurance Research Database of Taiwan. Among 24,975 patients with MI, 2686 case patients with pneumonia requiring hospitalization were age- and sex-matched with 10,726 control patients using the incidence density sampling approach. Duration and dosage of statin use were obtained from pharmaceutical claims. Conditional logistic regression analyses were used to estimate the risk of hospitalization for pneumonia associated with statin use adjusted for patient's demographics, medical conditions and prescribed medications. RESULTS: Statin use was associated with a 15% reduced risk of pneumonia requiring hospitalization among MI patients (adjusted odds ratio [aOR] = 0.85, 95% confidence interval [CI] = 0.77-0.95, P = 0.004). The association was more significant for MI patients unexposed to statin pretreatment (aOR = 0.76, 95% CI = 0.64-0.90, P = 0.001). Statins also exhibited favorable benefits in a time- and dose-dependent manner. The results were consistent in various subgroup analysis of the patients who were female, age >= 65 years, a low CHADS2 (i.e. congestive heart failure, hypertension, diabetes mellitus, previous stroke and age > 75 years old) score, and fewer comorbidities. Atorvastatin, fluvastatin and simvastatin were the most common prescribed statins and had similar effects. CONCLUSIONS: Statins might be considered as an adjunctive therapy to reduce the risk of hospitalization for pneumonia for MI patients under thorough evaluation of individual comorbidities, previous statin use and optimal dosage. PMID- 26823084 TI - Synthesis, characterization, and properties of a benzofuran-based cage-shaped borate: photo activation of Lewis acid catalysts. AB - A cage-shaped borate with benzofuran moieties was synthesized. This borate showed a higher degree of catalytic activity for Mukaiyama-aldol type reactions than a simple benzene-based cage-shaped borate induced by self-aggregation. Moreover, the exposure of the complex to black-light irradiation enhanced the catalytic activity. PMID- 26823083 TI - Dissecting protein architecture with communication blocks and communicating segment pairs. AB - BACKGROUND: Proteins adapt to environmental conditions by changing their shape and motions. Characterising protein conformational dynamics is increasingly recognised as necessary to understand how proteins function. Given a conformational ensemble, computational tools are needed to extract in a systematic way pertinent and comprehensive biological information. RESULTS: Here, we present a method, Communication Mapping (COMMA), to decipher the dynamical architecture of a protein. The method first extracts residue-based dynamic properties from all-atom molecular dynamics simulations. Then, it integrates them in a graph theoretic framework, where it identifies groups of residues or protein regions that mediate short- and long-range communication. COMMA introduces original concepts to contrast the different roles played by these regions, namely communication blocks and communicating segment pairs, and evaluates the connections and communication strengths between them. We show the utility and capabilities of COMMA by applying it to three archetypal proteins, namely protein A, the tyrosine kinase KIT and the tumour suppressor p53. CONCLUSION: Our method permits to compare in a direct way the dynamical behaviour either of proteins with different characteristics or of the same protein in different conditions. It is useful to identify residues playing a key role in protein allosteric regulation and to explain the effects of deleterious mutations in a mechanistic way. COMMA is a fully automated tool with broad applicability. It is freely available to the community at www.lcqb.upmc.fr/COMMA . PMID- 26823082 TI - Epigenetic impact of infection on carcinogenesis: mechanisms and applications. AB - Viral and bacterial infections are involved in the development of human cancers, such as liver, nasopharyngeal, cervical, head and neck, and gastric cancers. Aberrant DNA methylation is frequently present in these cancers, and some of the aberrantly methylated genes are causally involved in cancer development and progression. Notably, aberrant DNA methylation can be present even in non cancerous or precancerous tissues, and its levels correlate with the risk of cancer development, producing a so-called 'epigenetic field for cancerization'. Mechanistically, most viral or bacterial infections induce DNA methylation indirectly via chronic inflammation, but recent studies have indicated that some viruses have direct effects on the epigenetic machinery of host cells. From a translational viewpoint, a recent multicenter prospective cohort study demonstrated that assessment of the extent of alterations in DNA methylation in non-cancerous tissues can be used to predict cancer risk. Furthermore, suppression of aberrant DNA methylation was shown to be a useful strategy for cancer prevention in an animal model. Here, we review the involvement of aberrant DNA methylation in various types of infection-associated cancers, along with individual induction mechanisms, and we discuss the application of these findings for cancer prevention, diagnosis, and therapy. PMID- 26823085 TI - Flexible and Stretchable Optoelectronic Devices using Silver Nanowires and Graphene. AB - Many studies have accompanied the emergence of a great interest in flexible or/and stretchable devices for new applications in wearable and futuristic technology, including human-interface devices, robotic skin, and biometric devices, and in optoelectronic devices. Especially, new nanodimensional materials enable flexibility or stretchability to be brought based on their dimensionality. Here, the emerging field of flexible devices is briefly introduced using silver nanowires and graphene, which are famous nanomaterials for the use of transparent conductive electrodes, as examples, and their unique functions originating from the intrinsic property of these nanomaterials are highlighted. It is thought that this work will evoke more interest and idea exchanges in this emerging field and hopefully can trigger a breakthrough on a new type of optoelectronics and optogenetic devices in the near future. PMID- 26823086 TI - Anatomical and clinical aspects of Klinefelter's syndrome. AB - Klinefelter's syndrome, the most common sex disorder associated with chromosomal aberrations, is characterized by a plethora of clinical features. Parameters for diagnosis of the syndrome are constantly expanding as new anatomical and hormonal abnormalities are noted, yet Klinefelter's remains underdiagnosed and underreported. This review outlines the key anatomical characteristics associated with the syndrome, which are currently used for clinical diagnosis, or may provide means for improving diagnosis in the future. Clin. Anat. 29:606-619, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26823087 TI - Psychiatric governance, volkisch corporatism, and the German Research Institute of Psychiatry in Munich (1912-26). Part 1. AB - This is the first of two articles exploring in depth some of the early organizational strategies that were marshalled in efforts to found and develop the German Research Institute of Psychiatry (Deutsche Forschungsanstalt fur Psychiatrie) in 1917. After briefly discussing plans for a German research institute before World War I, the article examines the political strategies and networks that Emil Kraepelin used to recruit support for the institute. It argues that his efforts at psychiatric governance can best be understood as a form of volkisch corporatism which sought to mobilize and coordinate a group of players in the service of higher biopolitical and hygienic ends. The article examines the wartime arguments used to justify the institute, the list of protagonists actively engaged in recruiting financial and political support, the various social, scientific and political networks that they exploited, and the local contingencies that had to be negotiated in order to found the research institute. PMID- 26823088 TI - Expanded indications for bariatric surgery: should patients on chronic steroids be offered bariatric procedures? AB - BACKGROUND: Patients who take chronic corticosteroids are increasingly referred for bariatric surgery. Little is known about their clinical outcomes. OBJECTIVE: Determine whether chronic steroid use is associated with increased morbidity and mortality after stapled bariatric procedures. SETTING: American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. METHODS: All patients who underwent laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass and were reported to the ACS-NSQIP from 2011 to 2013 were reviewed. Patients were grouped based on type of surgery and history of chronic steroid use. Primary outcome measures were mortality and serious morbidity in the first 30 days. Regression analyses were used to determine predictors of outcome. RESULTS: Of 23,798 patients who underwent laparoscopic sleeve gastrectomy and 38,184 who underwent Roux-en-Y gastric bypass, 385 (1.6%) and 430 (1.1%), respectively, were on chronic steroids. Patients on chronic steroids had a 3.4 times increased likelihood of dying within 30 days (95% confidence interval 1.4-8.1, P = .007), and 2-fold increased odds of serious complications (95% confidence interval 1.2-2.3, P = .008), regardless of surgery type. In multivariate regression, steroid usage remained an independent predictor of mortality and serious complications. CONCLUSION: In a large, nationally representative patient database, steroid use independently predicted mortality and serious postoperative complications after stapled bariatric procedures. Surgeons should be cautious about offering stapled bariatric procedures to patients on chronic steroids. PMID- 26823089 TI - Sleeve gastrectomy surgery in obese patients post-organ transplantation. AB - BACKGROUND: Among organ transplant recipients, a common side effect of immunosuppressive therapy is the development of obesity, which affects a third of the patients within 3 years after transplantation. Bariatric surgery represents a possible surgical option for weight loss among posttransplant patients. OBJECTIVES: The aim of this study was to examine percent excess weight loss (%EWL), and percent weight loss (%WL) and perioperative and postoperative complications in posttransplant obese patients after sleeve gastrectomy (SG) compared with nontransplant patients. We hypothesize that transplant patients who undergo SG will not significantly differ in their perioperative or postoperative complications or in their %EWL and %WL compared with nontransplant patients who undergo SG. The second aim was to evaluate the impact of SG on graft function and immunosuppressive therapy in transplant patients. SETTING: University hospital. METHODS: Among 500 consecutive patients who underwent SG from January 2008 to June 2014, 10 patients were organ transplant recipients. The following variables were compared between groups: patient demographic characteristics and co morbidities, type of transplant surgery, date of transplant surgery, pretransplant body mass index (BMI), date of bariatric surgery, prebariatric surgery BMI, operative time, length of hospitalization, postoperative complications, and change in BMI, %EWL, and %WL. Data were also collected on renal, liver, and pancreas graft function parameters and changes in immunosuppressive medications. RESULTS: Six patients had a kidney transplant, 2 patients had a liver transplant, and 2 had a pancreas transplant. No significant differences were observed in %EWL or %WL at 6 and 12 months follow-up between transplant and nontransplant patients. No transplant patients were lost to follow up at 6 and 12 months. Among nontransplant patients, 36.7% and 35.7% were lost to follow-up at 6 and 12 months, respectively. No postoperative complications were registered in the transplant group. SG did not negatively affect the graft function. CONCLUSION: Initials results found that there were no significant differences in %EWL or %WL at 6 and 12 months follow-up between transplant and nontransplant patients. There were also no perioperative and postoperative complications among transplant patients after SG. PMID- 26823090 TI - Does bariatric surgery really prevent deterioration of renal function? AB - BACKGROUND: Obesity is related to impaired renal function; bariatric surgery is associated with an improvement in renal function. OBJECTIVES: We investigated obesity-related changes in renal function after bariatric surgery and identified related clinical factors. SETTING: Soonchunhyang University Seoul Hospital, Korea. METHODS: From December 2011 to February 2014, 493 consecutive patients who met the criteria underwent bariatric surgery. Of these patients, 136 patients were enrolled. The exclusion criteria were as follows: revisional bariatric surgery, laparoscopic adjustable gastric banding, significant chronic kidney disease, macroalbuminuria, nephrotic range proteinuria, and absence of laboratory data on renal function. Overall, there were 126 patients with Roux-en-Y gastric bypass and 10 with sleeve gastrectomy. Preoperative and postoperative 1-year renal function was evaluated by the estimated glomerular filtration rate, urinary albumin-to-creatinine ratio (UACR), and urinary protein-to-creatinine ratio (UPCR). RESULTS: Of 136 patients, 101 were women, and the mean age was 35.9+/ 11.2 years. UACR was significantly lower postoperatively than preoperatively (27.0+/-47.2 versus 9.0+/-8.6 mg/g; P<.001). Microalbuminuria was present in 22.1% of patients preoperatively, decreasing to 4.4% 1-year postoperatively. A significant reduction was observed in the UPCR (90.7+/-101.2 versus 64.6+/-34.8 mg/g; P = .004). The mean value of estimated glomerular filtration rate improved from 117.8 to 119.6 mL/min/1.73 m(2), although this was not significant. CONCLUSION: In obese patients, bariatric surgery significantly improves microalbuminuria and decreases the UACR and UPCR. Therefore, bariatric surgery should be considered as an early treatment for obesity with renal impairment and may prevent the progression to overt disease. PMID- 26823091 TI - "Dual-remission" after Roux-en-Y gastric bypass surgery: Glycemic variability cannot always be improved in Chinese obese patients with type 2 diabetes. AB - BACKGROUND: Glycemic variability after Roux-en-Y Gastric Bypass (RYGB) has not been adequately examined in Chinese obese patients with type 2 diabetes (T2D). OBJECTIVE: We aimed to evaluate glucose variability after RYGB by continuous glucose monitoring (CGM) and then evaluate the remission rate based on the complete diabetes remission criteria combined with normal ranges of CGM for the Chinese population, which we defined as "dual-remission." SETTING: The study was done at our academic university-affiliated hospital. METHODS: Over a 3-day period, CGM was performed on 43 Chinese obese T2D patients combined with a mixed meal test before and 1 year after RYGB. Mean amplitude of glucose excursions (MAGE), standard deviations (SD), and the time that patients' blood glucose levels were>=7.0 mmol/L,>=7.8 mmol/L,>=11.1 mmol/L, and<=3.9 mmol/L within 24 hours was analyzed. Multiple logistic regression analyses were used to identify predictors of "dual-remission." RESULTS: Complete diabetes remission was achieved in 27 patients (62.8%) 1 year after RYGB. However, MAGE didn't change in the group, and only 18.6% patients met "dual-remission." Compared with patients in the complete remission group, patients in the dual-remission group had a shorter duration of diabetes, younger age, lower glycated hemoglobin (HbA1c) level, and no insulin usage at baseline. Correlation analysis showed MAGE after RYGB was positively correlated with diabetes duration (r = .43, P<.01). Multiple logistic regressions indicated a shorter duration was associated with a higher possibility to achieve dual-remission after adjusting for age, gender, HbA1c, and insulin therapy. CONCLUSION: Glucose variability can't be effectively improved in most Chinese obese diabetic patients after RYGB. Shorter diabetes duration was associated with higher possibility to achieve "dual-remission." PMID- 26823092 TI - Caramel as a Model System for Evaluating the Roles of Mechanical Properties and Oral Processing on Sensory Perception of Texture. AB - Food formulation can have a significant impact on texture perception during oral processing. We hypothesized that slight modifications to caramel formulations would significantly alter mechanical and masticatory parameters, which can be used to explain differences in texture perception. A multidisciplinary approach was applied by evaluating relationships among mechanical properties, sensory texture, and oral processing. Caramels were utilized as a highly adhesive and cohesive model system and the formulation was adjusted to generate distinct differences in sensory hardness and adhesiveness. Descriptive analysis was used to determine sensory texture, and mechanical properties were evaluated by oscillatory rheology, creep recovery, and pressure sensitive tack measurements. Oral processing was measured by determining activity of anterior temporalis and masseter muscles via electromyography and tracking jaw movement during chewing. The substitution of agar or gelatin for corn syrup at 0.6% w/w of the total formulation resulted in increased sensory hardness and decreased adhesiveness. Creep recovery and pressure sensitive tack testing were more effective at differentiating among treatments than oscillatory rheology. Hardness correlated inversely with creep compliance, and both stickiness and tooth adhesiveness correlated with pressure sensitive adhesive force. Harder samples, despite being less adhesive, were associated with increased muscle activity and jaw movement during mastication. Tooth packing, not linked with any mechanical property, correlated with altered jaw movement. The combination of material properties and oral processing parameters were able to explain all sensory texture differences in a highly adhesive food. PMID- 26823093 TI - DNA methylation outliers in normal breast tissue identify field defects that are enriched in cancer. AB - Identifying molecular alterations in normal tissue adjacent to cancer is important for understanding cancer aetiology and designing preventive measures. Here we analyse the DNA methylome of 569 breast tissue samples, including 50 from cancer-free women and 84 from matched normal cancer pairs. We use statistical algorithms for dissecting intra- and inter-sample cellular heterogeneity and demonstrate that normal tissue adjacent to breast cancer is characterized by tens to thousands of epigenetic alterations. We show that their genomic distribution is non-random, being strongly enriched for binding sites of transcription factors specifying chromatin architecture. We validate the field defects in an independent cohort and demonstrate that over 30% of the alterations exhibit increased enrichment within matched cancer samples. Breast cancers highly enriched for epigenetic field defects, exhibit adverse clinical outcome. Our data support a model where clonal epigenetic reprogramming towards reduced differentiation in normal tissue is an important step in breast carcinogenesis. PMID- 26823095 TI - QT interval, corrected for heart rate, is associated with HbA1c concentration and autonomic function in diabetes. AB - AIMS: To examine QT intervals corrected for heart rate (QTc) in adolescents with Type 1 diabetes compared with control subjects, and to determine associations with metabolic control and autonomic function. METHODS: Resting electrocardiogram recordings of 142 adolescents with Type 1 diabetes [mean (sd) age 15.3 (2.0) years, diabetes duration 9.0 (3.5) years, HbA1c 71 (17) mmol/mol or 8.7 (1.6)%] and 125 control subjects [mean (sd) age 15.7 (2.5) years] were used to calculate QTc duration and derive mean heart rate and heart rate variability (HRV) values. Linear and logistic regression models were used to examine the associations between QTc, metabolic control and autonomic function (HRV and pupillary function). RESULTS: QTc duration was not significantly different between subjects with Type 1 diabetes and control subjects (mean duration 392 vs 391 ms; P = 0.65). In the Type 1 diabetes group, QTc was positively associated with HbA1c [beta = 4 (95% CI 2, 6); P < 0.001] and inversely associated with severe hypoglycaemic events [beta = -10 (95% CI -20,-2); P = 0.01], less insulin/kg [beta = -12 (95% CI -22, -2); P = 0.024] and less HRV. In the Type 1 diabetes group, QTc in the highest quintile (>=409 ms) vs quintiles 1-4 had more pupillary abnormalities (83 vs 56%; P = 0.03), lower pupillary maximum constriction velocity (4.8 vs 5.3 mm/s; P = 0.04), higher heart rate (78 vs 72 beats per min; P = 0.02) and lower HRV (standard deviation of mean NN intervals 4.0 vs 4.3 ms, P = 0.004 and root-mean-square difference of successive NN intervals 3.7 vs 4.1 ms; P = 0.004). CONCLUSIONS: Although there are concerns about hypoglycaemia in general in people with Type 1 diabetes, chronic hyperglycaemia, rather than intermittent hypoglycaemia, appears to be more deleterious to autonomic cardiac function, even in adolescence. Longer QTc was associated with higher HbA1c concentration, lower risk of hypoglycaemia and autonomic dysfunction. Longitudinal studies are warranted. PMID- 26823094 TI - Morbidity and mortality after bilateral simultaneous total knee arthroplasty in a fast-track setting. AB - Background and purpose - The safety aspects of bilateral simultaneous total knee arthroplasty (BSTKA) are still debated. In this retrospective single-center study, we investigated early morbidity and mortality following BSTKA in a modern fast-track setting. We also identified risk factors for re-admission within 90 days and for a length of stay (LOS) of more than 5 days. Patients and methods - 284 patients were selected to receive BSTKA at our institution from 2008 through 2014 in a well-described, standardized fast-track setup (Husted 2012a, b). All re admissions within 90 days were identified and mortality rates and time until death were recorded. Transfusion rates and numbers of transfusions were also recorded. Logistic regression analysis was used to identify risk factors for re admission within 90 days, and also for a LOS of more than 5 days. Results - 90 day mortality was 0%. 10% of the patients were re-admitted within 90 days. Median time to re-admission was 18 (3-75) days. 153 patients (54%) received postoperative blood transfusions. An ASA score of 3 was identified as an independent risk factor for re-admission within 90 days (OR = 5, 95% CI: 1.3-19) and for LOS of > 5 days (OR = 6, 95% CI: 1.6-21). Higher BMI was a weak risk factor for re-admission within 90 days. Interpretation - BSTKA in selected patients without cardiopulmonary disease in a fast-track setting appears to be safe with respect to early postoperative morbidity and mortality. Surgeons should be aware that patients with an ASA score of 3 have an increased risk of re admission and a prolonged length of stay, while patients with higher BMI have an increased risk of re-admission following BSTKA. PMID- 26823096 TI - The effect of mood on false memory for emotional DRM word lists. AB - In the present study, we investigated the effect of participants' mood on true and false memories of emotional word lists in the Deese-Roediger-McDermott (DRM) paradigm. In Experiment 1, we constructed DRM word lists in which all the studied words and corresponding critical lures reflected a specified emotional valence. In Experiment 2, we used these lists to assess mood-congruent true and false memory. Participants were randomly assigned to one of three induced-mood conditions (positive, negative, or neutral) and were presented with word lists comprised of positive, negative, or neutral words. For both true and false memory, there was a mood-congruent effect in the negative mood condition; this effect was due to a decrease in true and false recognition of the positive and neutral words. These findings are consistent with both spreading-activation and fuzzy-trace theories of DRM performance and have practical implications for our understanding of the effect of mood on memory. PMID- 26823097 TI - Equilibration and nonclassicality of a double-well potential. AB - A double well loaded with bosonic atoms represents an ideal candidate to simulate some of the most interesting aspects in the phenomenology of thermalisation and equilibration. Here we report an exhaustive analysis of the dynamics and steady state properties of such a system locally in contact with different temperature reservoirs. We show that thermalisation only occurs 'accidentally'. We further examine the nonclassical features and energy fluxes implied by the dynamics of the double-well system, thus exploring its finite-time thermodynamics in relation to the settlement of nonclassical correlations between the wells. PMID- 26823098 TI - The implications of reduced metabolic rate in resource-limited corals. AB - Many organisms exhibit depressed metabolism when resources are limited, a change that makes it possible to balance an energy budget. For symbiotic reef corals, daily cycles of light and periods of intense cloud cover can be chronic causes of food limitation through reduced photosynthesis. Furthermore, coral bleaching is common in present-day reefs, creating a context in which metabolic depression could have beneficial value to corals. In the present study, corals (massive Porites spp.) were exposed to an extreme case of resource limitation by starving them of food and light for 20 days. When resources were limited, the corals depressed area-normalized respiration to 37% of initial rates, and coral biomass declined to 64% of initial amounts, yet the corals continued to produce skeletal mass. However, the declines in biomass cannot account for the declines in area normalized respiration, as mass-specific respiration declined to 30% of the first recorded time point. Thus, these corals appear to be capable of metabolic depression. It is possible that some coral species are better able to depress metabolic rates than others; such variation could explain differential survival during conditions that limit resources (e.g. shading). Furthermore, we found that maintenance of existing biomass, in part, supports the production of skeletal mass. This association could be explained if maintenance supplies needed energy (e.g. ATP) or inorganic carbon (i.e. CO2) that otherwise limits the production of skeletal mass. Finally, the observed metabolic depression can be explained as a change in pool sizes, and does not require a change in metabolic rules. PMID- 26823099 TI - The effects of multiple obstacles on the locomotor behavior and performance of a terrestrial lizard. AB - Negotiation of variable terrain is important for many small terrestrial vertebrates. Variation in the running surface resulting from obstacles (woody debris, vegetation, rocks) can alter escape paths and running performance. The ability to navigate obstacles likely influences survivorship through predator evasion success and other key ecological tasks (finding mates, acquiring food). Earlier work established that running posture and sprint performance are altered when organisms face an obstacle, and yet studies involving multiple obstacles are limited. Indeed, some habitats are cluttered with obstacles, whereas others are not. For many species, obstacle density may be important in predator escape and/or colonization potential by conspecifics. This study examines how multiple obstacles influence running behavior and locomotor posture in lizards. We predict that an increasing number of obstacles will increase the frequency of pausing and decrease sprint velocity. Furthermore, bipedal running over multiple obstacles is predicted to maintain greater mean sprint velocity compared with quadrupedal running, thereby revealing a potential advantage of bipedalism. Lizards were filmed running through a racetrack with zero, one or two obstacles. Bipedal running posture over one obstacle was significantly faster than quadrupedal posture. Bipedal running trials contained fewer total strides than quadrupedal ones. But on addition of a second obstacle, the number of bipedal strides decreased. Increasing obstacle number led to slower and more intermittent locomotion. Bipedalism provided clear advantages for one obstacle, but was not associated with further benefits for an additional obstacle. Hence, bipedalism helps mitigate obstacle negotiation, but not when numerous obstacles are encountered in succession. PMID- 26823100 TI - Salt preferences of honey bee water foragers. AB - The importance of dietary salt may explain why bees are often observed collecting brackish water, a habit that may expose them to harmful xenobiotics. However, the individual salt preferences of water-collecting bees were not known. We measured the proboscis extension reflex (PER) response of Apis mellifera water foragers to 0-10% w/w solutions of Na, Mg and K, ions that provide essential nutrients. We also tested phosphate, which can deter foraging. Bees exhibited significant preferences, with the most PER responses for 1.5-3% Na and 1.5% Mg. However, K and phosphate were largely aversive and elicited PER responses only for the lowest concentrations, suggesting a way to deter bees from visiting contaminated water. We then analyzed the salt content of water sources that bees collected in urban and semi-urban environments. Bees collected water with a wide range of salt concentrations, but most collected water sources had relatively low salt concentrations, with the exception of seawater and swimming pools, which had >0.6% Na. The high levels of PER responsiveness elicited by 1.5-3% Na may explain why bees are willing to collect such salty water. Interestingly, bees exhibited high individual variation in salt preferences: individual identity accounted for 32% of variation in PER responses. Salt specialization may therefore occur in water foragers. PMID- 26823101 TI - Elevated osmolytes in rainbow smelt: the effects of urea, glycerol and trimethylamine oxide on muscle contractile properties. AB - Rainbow smelt, Osmerus mordax, experience a wide range of temperatures in their native habitat. In response to cold, smelt express anti-freeze proteins and the osmolytes glycerol, trimethylamine N-oxide (TMAO) and urea to avoid freezing. The physiological influences of these osmolytes are not well understood. Urea destabilizes proteins, while TMAO counteracts the protein-destabilizing forces of urea. The influence of glycerol on muscle function has not been explored. We examined the effects of urea, glycerol and TMAO through muscle mechanics experiments with treatments of the three osmolytes at physiological concentrations. Experiments were carried out at 10 degrees C. The contractile properties of fast-twitch muscle bundles were determined in physiological saline and in the presence of 50 mmol l(-1)urea, 50 mmol l(-1)TMAO and/or 200 mmol l( 1)glycerol in saline. Muscle exposed to urea and glycerol produced less force and displayed slower contractile properties. However, treatment with TMAO led to higher force and faster relaxation by muscle bundles. TMAO increased power production during cyclical activity, while urea and glycerol led to reduced oscillatory power output. When muscle bundles were exposed to a combination of the three osmolytes, they displayed little change in contraction kinetics relative to control, although power output under lower oscillatory conditions was enhanced while maximum power output was reduced. The results suggest that maintenance of muscle function in winter smelt requires a balanced combination of urea, glycerol and TMAO. PMID- 26823102 TI - Biomechanical control of vocal plasticity in an echolocating bat. AB - Many animal species adjust the spectral composition of their acoustic signals to variable environments. However, the physiological foundation of such spectral plasticity is often unclear. The source-filter theory of sound production, initially established for human speech, applies to vocalizations in birds and mammals. According to this theory, adjusting the spectral structure of vocalizations could be achieved by modifying either the laryngeal/syringeal source signal or the vocal tract, which filters the source signal. Here, we show that in pale spear-nosed bats, spectral plasticity induced by moderate level background noise is dominated by the vocal tract rather than the laryngeal source signal. Specifically, we found that with increasing background noise levels, bats consistently decreased the spectral centroid of their echolocation calls up to 3.2 kHz, together with other spectral parameters. In contrast, noise-induced changes in fundamental frequency were small (maximally 0.1 kHz) and were inconsistent across individuals. Changes in spectral centroid did not correlate with changes in fundamental frequency, whereas they correlated negatively with changes in call amplitude. Furthermore, while bats consistently increased call amplitude with increasing noise levels (the Lombard effect), increases in call amplitude typically did not lead to increases in fundamental frequency. In summary, our results suggest that at least to a certain degree echolocating bats are capable of adjusting call amplitude, fundamental frequency and spectral parameters independently. PMID- 26823103 TI - A flavanoid component of chocolate quickly reverses an imposed memory deficit. AB - The ability to remember is influenced by environmental and lifestyle factors, such as stress and diet. A flavanol contained in chocolate, epicatechin (Epi), has been shown to enhance long-term memory (LTM) formation in Lymnaea. Combining two stressors (low-calcium pond water and crowding) blocks learning and all forms of memory; that is, this combination of environmentally relevant stressors creates a memory-unfriendly state. We tested the hypothesis that Epi will immediately reverse the memory-unfriendly state, i.e. that snails in the memory deficit state when trained in Epi will immediately become competent to learn and form memory. We found that Epi not only reverses the memory-deficit state but also further enhances LTM formation. Thus, a naturally occurring bioactive plant compound can overcome a memory-unfriendly state. This supports the idea that bioactive substances may mitigate memory-making deficits that, for example, occur with ageing. PMID- 26823104 TI - Proteomic data reveal a physiological basis for costs and benefits associated with thermal acclimation. AB - Physiological adaptation through acclimation is one way to cope with temperature changes. Biochemical studies on acclimation responses in ectotherms have so far mainly investigated consequences of short-term acclimation at the adult stage and focussed on adaptive responses. Here, we assessed the consequences of rearing Drosophila melanogasterat low (12 degrees C), benign (25 degrees C) and high (31 degrees C) temperatures. We assessed cold and heat tolerance and obtained detailed proteomic profiles of flies from the three temperatures. The proteomic profiles provided a holistic understanding of the underlying biology associated with both adaptive and non-adaptive temperature responses. Results show strong benefits and costs across tolerances: rearing at low temperature increased adult cold tolerance and decreased adult heat tolerance and vice versa with development at high temperatures. In the proteomic analysis, we were able to identify and quantify a large number of proteins compared with previous studies on ectotherms (1440 proteins across all replicates and rearing regimes), enabling us to extend the proteomic approach using enrichment analyses. This gave us detailed information on individual proteins, as well as pathways affected by rearing temperature, pinpointing potential mechanisms responsible for the strong costs and benefits of rearing temperature on functional phenotypes. Several well-known heat shock proteins, as well as proteins not previously associated with thermal stress, were among the differentially expressed proteins. Upregulation of proteasome proteins was found to be an important adaptive process at high-stress rearing temperatures, and occurs at the expense of downregulation of basal metabolic functions. PMID- 26823105 TI - [Glucose renal excretion as diabetes treatment: From an old diagnostic method to a new way of treatment]. PMID- 26823106 TI - [Health challenges of demographic change]. PMID- 26823107 TI - [Leukemic transformation of Langerhans cell sarcoma]. PMID- 26823108 TI - [Occupational diseases treated at Parc de Salut Mar (Barcelona, Spain), 2010 2014]. PMID- 26823109 TI - [Liver hydatid disease: Still a problem]. PMID- 26823110 TI - Multiview hyperspectral topography of tissue structural and functional characteristics. PMID- 26823111 TI - The utility of VWF multimer analysis in response to the desmopressin administration for the diagnosis of severe type 1 von Willebrand disease. PMID- 26823112 TI - Nurses' knowledge of advance directives and perceived confidence in end-of-life care: a cross-sectional study in five countries. AB - Nurses' knowledge regarding advance directives may affect their administration and completion in end-of-life care. Confidence among nurses is a barrier to the provision of quality end-of-life care. This study investigated nurses' knowledge of advance directives and perceived confidence in end-of-life care, in Hong Kong, Ireland, Israel, Italy and the USA using a cross-sectional descriptive design (n = 1089). In all countries, older nurses and those who had more professional experience felt more confident managing patients' symptoms at end-of-life and more comfortable stopping preventive medications at end-of-life. Nurses in the USA reported that they have more knowledge and experience of advance directives compared with other countries. In addition, they reported the highest levels of confidence and comfort in dealing with end-of-life care. Although legislation for advance directives does not yet exist in Ireland, nurses reported high levels of confidence in end-of-life care. PMID- 26823114 TI - Estimating healthcare resource use associated with the treatment of metastatic melanoma in eight countries. AB - Objectives Studies reporting healthcare resourse use (HRU) for melanoma, one of the most costly cancers to treat, are limited. Using consistent, robust methodology, this study estimated HRU associated with the treatment of metastatic melanoma in eight countries. Methods Using published literature and clinician input, treatment phases were identified: active systemic treatment (pre progression); disease progression; best supportive care (BSC)/palliative care; and terminal care. HRU elements were identified for each phase and estimates of the magnitude and frequency of use in clinical practice were obtained through country-specific Delphi panels, comprising healthcare professionals with experience in oncology (n = 8). Results Medical oncologists are the key care providers for patients with metastatic melanoma, although in Germany dermato oncologists also lead care. During the active systemic treatment phase, each patient was estimated to require 0.83-2 consultations with a medical oncologist/month across countries; the median number of such assessments in 3 months was highest in Canada (range = 3.5-5) and lowest in France, the Netherlands and Spain (1). Resource use during the disease progression phase was intensive and similar across countries: all patients were estimated to consult with medical oncologists and 10-40% with a radiation oncologist; up to 40% were estimated to require a brain MRI scan. During the BSC/palliative care phase, all patients were estimated to consult with medical oncologists, and most to consult with a primary care physician (40-100%). Limitations Panelists were from centers of excellence, thus results may not reflect care within smaller hospitals; data obtained from experts may be less variable than data from broader clinical practice. Treatments for metastatic melanoma are continually emerging, thus some elements of our work could be superseded. Conclusions HRU estimates were substantial and varied across countries for some resources. These data could be used with country-specific costs to elucidate costs for the management of metastatic melanoma. PMID- 26823113 TI - At least two Fc Neu5Gc residues of monoclonal antibodies are required for binding to anti-Neu5Gc antibody. AB - Two non-human glycan epitopes, galactose-alpha-1,3-galactose (alpha-gal) and Neu5Gc-alpha-2-6-galactose (Neu5Gc) have been shown to be antigenic when attached to Fab oligosaccharides of monoclonal antibodies (mAbs) , while alpha-gal attached to Fc glycans was not. However, the antigenicity of Neu5Gc on the Fc glycans remains unclear in the context that most mAbs carry only Fc glycans. After studying two clinical mAbs carrying significant amounts of Fc Neu5Gc, we show that their binding activity with anti-Neu5Gc antibody resided in a small subset of mAbs carrying two or more Fc Neu5Gc, while mAbs harboring only one Neu5Gc showed no reactivity. Since most Neu5Gc epitopes were distributed singly on the Fc of mAbs, our results suggest that the potential antigenicity of Fc Neu5Gc is low. Our study could be referenced in the process design and optimization of mAb production in murine myeloma cells and in the quality control of mAbs for industries and regulatory authorities. PMID- 26823115 TI - Influence of living environments and working status on low back pain for survivors of the Great East Japan Earthquake. AB - BACKGROUND: The Great East Japan Earthquake and devastating Tsunami caused irreparable damage on the northeastern coast of Japan. This study aimed to examine the influencing factors of "Living environment" and "Working status" on low back pain for the survivors of the earthquake evaluated by a self-report questionnaire. METHODS: Between 2011 and 2013, survivors replied to the self report questionnaire, and 986 people consented to join this study. The living environment was divided into 3 categories (1. Living in the same house as before the earthquake, 2. Living in a safe shelter or temporary small house, 3. Living in a house of relatives or apartment house) and working status was divided into 5 categories (1. Unemployed before the earthquake, 2. Unemployed after the earthquake, 3. Decrease in income, 4. Different occupation after the earthquake, 5. The same occupation as before the earthquake). Age, gender, living areas, past history of arthritis, arthropathy, osteoporosis, sleep disturbance, psychological distress, and economic status were considered as confounding factors. Generalized estimating regression models with logit link function were used because outcome variables are repeatedly measured and binomial. We evaluated the correlation between the presence/severity of low back pain over time and housing status/working status at 1 year after the earthquake. RESULTS: There were no significant differences between age, gender, living areas, working status, or living environment before or after the earthquake. There was no significant difference in the risk of having low back pain in living environment or gender. There was significant difference in the risk of having low back pain in those with "Decrease in income" (OR = 1.93, 95% CI = 1.23-3.03) and "The same occupation as before the earthquake" (OR = 1.67, 95% CI = 1.1-2.52). CONCLUSIONS: Though living environment has little effect, "Decrease in income" and "The same occupation as before the earthquake" have strong influences on low back pain. PMID- 26823116 TI - Understanding Mechanisms of Action of Beta-Blockers in Heart Failure With Reduced and Preserved Ejection Fraction. PMID- 26823117 TI - The PARADIGM of Influenza Vaccination in Heart Failure Patients. PMID- 26823118 TI - Death of the Heart Failure Clinical Investigator: Molecules and Receptors Win Nobel Prizes, Clinical Investigation Improves Survival. PMID- 26823119 TI - Growth control of oxygen stoichiometry in homoepitaxial SrTiO3 films by pulsed laser epitaxy in high vacuum. AB - In many transition metal oxides, oxygen stoichiometry is one of the most critical parameters that plays a key role in determining the structural, physical, optical, and electrochemical properties of the material. However, controlling the growth to obtain high quality single crystal films having the right oxygen stoichiometry, especially in a high vacuum environment, has been viewed as a challenge. In this work, we show that, through proper control of the plume kinetic energy, stoichiometric crystalline films can be synthesized without generating oxygen defects even in high vacuum. We use a model homoepitaxial system of SrTiO3 (STO) thin films on single crystal STO substrates. Physical property measurements indicate that oxygen vacancy generation in high vacuum is strongly influenced by the energetics of the laser plume, and it can be controlled by proper laser beam delivery. Therefore, our finding not only provides essential insight into oxygen stoichiometry control in high vacuum for understanding the fundamental properties of STO-based thin films and heterostructures, but expands the utility of pulsed laser epitaxy of other materials as well. PMID- 26823120 TI - Emergence of succinate dehydrogenase inhibitor resistance of Pyrenophora teres in Europe. AB - BACKGROUND: Net blotch caused by Pyrenophora teres is an important disease of barley worldwide. In addition to strobilurins (quinone ouside inhibitors) and azoles (demethylation inhibitors), succinate dehydrogenase inhibitors (SDHIs) are very effective fungicides for net blotch control. Recently, SDHI-resistant isolates have been found in the field. Intensive sensitivity monitoring programmes across Europe were carried out to investigate the situation concerning SDHI resistance in P. teres. RESULTS: The first isolates with a lower sensitivity to SDHIs registered in barley were found in Germany in 2012 and carried the B H277Y substitution in the succinate dehydrogenase enzyme. In 2013 and 2014, a significant increase in isolates with lower SDHI sensitivity was detected mainly in France and Germany, and the range of target-site mutations increased. Most of the resistant isolates carried the C-G79R substitution, which exhibits a strong impact on all SDHIs in microtitre tests. All SDHIs tested were shown to be cross resistant. Other substitutions are gaining in importance, e.g. C-N75S in France and D-D145G in Germany. So far, no double mutants in SDH genes have been detected. Glasshouse tests showed that SDHI-resistant isolates were still controlled by the SDHI fluxapyroxad when applied preventively. To date, most isolates with C-G79R substitution have not simultaneously carried the F129L change in cytochrome b, which causes resistance towards QoI fungicides at low to moderate levels. CONCLUSION: Several target-site mutations in the genes of subunits SDH-B, SDH-C and SDH-D with different impact on SDHI fungicides were detected. The pattern of mutations varied from year to year and between different regions. Strict resistance management strategies are recommended to maintain SDHIs as effective tools for net blotch control, especially in areas with low frequencies of resistant isolates. (c) 2016 Society of Chemical Industry. PMID- 26823121 TI - Testosterone modulates endothelial progenitor cells in rat corpus cavernosum. AB - OBJECTIVE: To investigate the effects of testosterone on cavernosal endothelial progenitor cells (EPCs) in a castrated rat model. MATERIALS AND METHODS: In all, 45 male Sprague-Dawley rats (12-weeks old) were divided into control, surgical castration, and castration with testosterone replacement groups. The rats were castrated under ketamine anaesthesia, and testosterone was administered by daily subcutaneous injection of 3 mg/kg testosterone propionate. The corpus cavernosum was obtained after perfusion with 10 mL saline via the abdominal aorta 4 weeks later. The expression of EPC-specific markers [cluster of differentiation 34 (CD34), fetal liver kinase 1 (Flk1), and vascular endothelial (VE)-cadherin] was evaluated by flow cytometry analysis and immunofluorescence staining. RESULTS: CD34+/Flk1+ and CD34+/VE-cadherin+ cells were detected in the cavernosal sinusoidal endothelial space. Flow cytometry analysis showed that CD34 and Flk1 double positive cells (EPCs) comprised ~3.79% of the corpus cavernosum in normal rats. The percentage of EPC marker-positive cells decreased significantly in the castration group (2.8%; P < 0.05) and was restored to 3.56% after testosterone supplementation. Confocal microscopy revealed that the numbers of CD34+/Flk1+ and CD34+/VE-cadherin+ cells decreased in castrated rats compared with controls, but were similar to control levels in rats receiving testosterone replacement. CONCLUSIONS: The EPC markers were expressed in the cavernosal sinusoidal endothelial space, and the numbers of resident EPCs were regulated by testosterone. These results suggest that testosterone replacement therapy may improve erectile function by modulating EPCs in patients with hypogonadism. PMID- 26823122 TI - Reductive Chlorination and Bromination of Ketones via Trityl Hydrazones. AB - A method is presented for the direct transformation of a ketone to the corresponding reduced alkyl chloride or bromide. The process involves the reaction of a ketone trityl hydrazone with tBuOCl to give a diazene which readily collapses to the alpha-chlorocarbinyl radical, reduction of which by a hydrogen atom source gives the alkyl chloride product. The use of N-bromosuccinimide provides the corresponding alkyl bromide. This unique transformation provides a reductive halogenation that complements Barton's redox-neutral vinyl halide synthesis. PMID- 26823123 TI - Lower attention to daily environment: a novel cue for detecting chronic horses' back pain? AB - Chronic pain is thought to affect patients' cognitive functioning, including attention. Loss of attention is likely to have an impact on the execution of daily tasks, and, therefore, to have negative effects. However, relationships between chronic pain and cognitive deficits are still debated. Pre-clinical studies using laboratory animals prove useful to model pain-related cognitive impairment, but animal models had to predict effects in the real world. This study investigates attentional engagement of domestic horses by comparing observations in a home setting and evaluations of vertebral disorders. We found that lower attentional engagement and the level of back disorders were correlated. Two different evaluation techniques of the state of horses' spines gave similar results. We suggest that novel animal models would prove useful for identifying spontaneous behaviours indicative of chronic pain. We suggest that more ethological studies in human patients' home environments would help to improve our understanding of the processes involved. Finally, these results yield interesting indications for evaluating animal welfare, as attentional engagement could become a reliable indicator of chronic pain and thus a useful tool for identification of suffering individuals. PMID- 26823124 TI - Protective effect of Rabdosia amethystoides (Benth) Hara extract on acute liver injury induced by Concanavalin A in mice through inhibition of TLR4-NF-kappaB signaling pathway. AB - Extract of Rabdosia amethystoides (Benth) Hara (ERA), a traditional Chinese medicine has antibacterial, antiviral, anti-tumor, anti-hepatitis and anti inflammatory properties. However, the hepatoprotective effects and molecular mechanisms of ERA on acute liver injury have not been fully elucidated. This study aims to investigate the anti-inflammatory effect and liver protection of ERA against the acute liver injury induced by Concanavalin A (Con A) and its underlying molecular mechanisms in mice. Mice received ERA (50, 100, 150 mg/kg body weight) by gavage before Con A intravenous administration. We found that ERA pretreatment was able to significantly reduce the elevated serum alanine and aspartate aminotransferase levels and liver necrosis in Con A-induced hepatitis. In addition, ERA treatment significantly decreased the myeloperoxidase, malondialdehyde levels and augmented superoxide dismutase level in the liver tissue, and also suppressed the secretion of proinflammatory cytokines in the serum, compared with Con A group by enzyme linked immunosorbent assay. Furthermore, we observed that ERA pretreatment can significantly decrease the expression level of Toll-like receptor (TLR) 4 mRNA or protein in liver tissues. Further results showed that ERA pretreatment was capable of attenuating the activation of the NF-kappaB pathway by inhibiting IkappaBalpha kinase and p65 phosphorylation in Con A-induced liver injury. Our results demonstrate that ERA pretreatment has hepatoprotective property against Con A-induced liver injury through inhibition of inflammatory mediators in mice. The beneficial effect of ERA may be mediated by the downregulation of TLR4 expression and the inhibition of NF-kappaB activation. PMID- 26823125 TI - Impact of a communication strategy on family satisfaction in the intensive care unit. AB - BACKGROUND: Family satisfaction of critically ill patients has gained increased interest as important indicator to evaluate the quality of care in the intensive care unit (ICU). The family satisfaction in the ICU questionnaire (FS-ICU 24) is a well-established tool to assess satisfaction in such settings. We tested the hypothesis that an intervention, aiming at improved communication between health professionals and patients' next of kin in the ICU improves family satisfaction, as assessed by FS-ICU 24. METHODS: Using a multicenter before-and-after study design, we evaluated medium-term effectiveness of VALUE, a recently proposed strategy aiming at improved communication. Satisfaction was assessed using the FS ICU 24 questionnaire. Performance-importance plots were generated in order to identify items highly correlated with overall satisfaction but with low individual score. RESULTS: A total of 163 completed family questionnaires in the pre-intervention and 118 in the post-intervention period were analyzed. Following the intervention, we observed: (1) a non-significant increase in family satisfaction summary score and sub-scores; (2) no decline in any individual family satisfaction item, and (3) improvement in items with high overall impact on satisfaction but quoted with low degree of satisfaction. CONCLUSION: No significant improvement in family satisfaction of critically ill adult patients could be found after implementing the VALUE strategy. Whether these results are due to insufficient training of the new strategy or a missing effect of the strategy in our socio-economic environment remains to be shown. PMID- 26823126 TI - A Suspected Choroidal Melanoma With Extraocular Extension in Pregnancy. PMID- 26823128 TI - Placebo effects of caffeine on maximal voluntary concentric force of the knee flexors and extensors. AB - INTRODUCTION: We examined the placebo effect of caffeine and the combined effect of caffeine and caffeine expectancy on maximal voluntary strength. METHODS: Fourteen men completed 4 randomized, single-blind experimental trials: (1) told caffeine, given caffeine (5 mg/kg) (CC); (2) told caffeine, given placebo (CP); (3) told placebo, given placebo (PP); and (4) told placebo, given caffeine (PC). Maximal voluntary concentric force and fatigue resistance of the knee flexors and extensors were measured using isokinetic dynamometry. RESULTS: A significant and equal improvement in peak concentric force was found in the CC and PC trials. Despite participants believing caffeine would evoke a performance benefit, there was no effect of CP. CONCLUSION: Caffeine caused an improvement in some aspects of muscle strength, but there was no additional effect of expectancy. Performance was poorer in participants who believed caffeine would have the greatest benefit, which highlights a link between expected ergogenicity, motivation, and personality characteristics. Muscle Nerve 54: 479-486, 2016. PMID- 26823129 TI - Remeasurement of (234)U Half-Life. AB - The half-life of (234)U has been measured using a novel approach. In this method, a uranium material was chemically purified from its thorium decay product at a well-known time. The ingrowth of the (230)Th daughter product in the material was followed by measuring the accumulated (230)Th daughter product relative to its parent (234)U nuclide using inductively coupled plasma mass spectrometry. Then, the (234)U decay constant and the respective half-life could be calculated using the radioactive decay equations based on the n((230)Th)/n((234)U) amount ratio. The obtained (234)U half-life is 244 900 +/- 670 years (k = 1), which is in good agreement with the previously reported results in the literature with comparable uncertainty. The main advantages of the proposed method are that it does not require the assumption of secular equilibrium between (234)U and (238)U. Moreover, the calculation is independent from the (238)U half-life value and its uncertainty. The suggested methodology can also be applied for the remeasurement of the half-lives of several other long-lived radionuclides. PMID- 26823127 TI - The effects of high fat diet and estradiol on hypothalamic prepro-QRFP mRNA expression in female rats. AB - Estradiol (E2) is a potent regulator of feeding behavior, body weight and adiposity in females. The hypothalamic neuropeptide, QRFP, is an orexigenic peptide that increases the consumption of high fat diet (HFD) in intact female rats. Therefore, the goal of the current series of studies was to elucidate the effects of E2 on the expression of hypothalamic QRFP and its receptors, QRFP-r1 and QRFP-r2, in female rats fed a HFD. Alterations in prepro-QRFP, QRFP-r1, and QRFP-r2 expression across the estrous cycle, following ovariectomy (OVX) and following estradiol benzoate (EB) treatment were assessed in the ventral medial nucleus of the hypothalamus/arcuate nucleus (VMH/ARC) and the lateral hypothalamus. In intact females, consumption of HFD increased prepro-QRFP and QRFP-r1 mRNA levels in the VMH/ARC during diestrus, a phase associated with increased food intake and low levels of E2. To assess the effects of diminished endogenous E2, rats were ovariectomized. HFD consumption and OVX increased prepro QRFP mRNA in the VMH/ARC. Ovariectomized rats consuming HFD expressed the highest levels of QRFP. In the third experiment, all rats received EB replacement every 4days following OVX to examine the effects of E2 on QRFP expression. Prepro-QRFP, QRFP-r1 and QRFP-r2 mRNA were assessed prior to and following EB administration. EB replacement significantly reduced prepro-QRFP mRNA expression in the VMH/ARC. Overall these studies support a role for E2 in the regulation of prepro-QRFP mRNA in the VMH/ARC and suggest that E2's effects on food intake may be via a direct effect on the orexigenic peptide, QRFP. PMID- 26823130 TI - Impact of serous retinal detachment on the efficacy of ranibizumab in diabetic macular oedema. PMID- 26823132 TI - RE: Vertebral Artery Dissection Presenting as Acute Cerebrovascular Accident. PMID- 26823131 TI - Factors associated with sinus bradycardia during crizotinib treatment: a retrospective analysis of two large-scale multinational trials (PROFILE 1005 and 1007). AB - Decreases in heart rate (HR) have been described in patients receiving crizotinib. We performed a large retrospective analysis of HR changes during crizotinib therapy. HRs from vital-sign data for patients with anaplastic lymphoma kinase (ALK)-positive nonsmall cell lung cancer enrolled in PROFILE 1005 and the crizotinib arm of PROFILE 1007 were analyzed. Sinus bradycardia (SB) was defined as HR <60 beats per minute (bpm). Magnitude and timing of HR changes were assessed. Potential risk factors for SB were investigated by logistic regression analysis. Progression-free survival (PFS) was evaluated according to HR decrease by <20 versus >= 20 bpm within the first 50 days of starting treatment. For the 1053 patients analyzed, the mean maximum postbaseline HR decrease was 25 bpm (standard deviation 15.8). Overall, 441 patients (41.9%) had at least one episode of postbaseline SB. The mean precrizotinib treatment HR was significantly lower among patients with versus without postbaseline SB (82.2 bpm vs. 92.6 bpm). The likelihood of experiencing SB was statistically significantly higher among patients with a precrizotinib treatment HR <70 bpm. PFS was comparable among patients with or without HR decrease of >= 20 bpm within the first 50 days of starting crizotinib. Decrease in HR is very common among patients on crizotinib. The likelihood of experiencing SB was statistically significantly higher among patients with a precrizotinib treatment HR <70 bpm. This is the first large-scale report investigating the association between treatment with a tyrosine kinase inhibitor and the development of bradycardia. HRs should be closely monitored during crizotinib treatment. PMID- 26823133 TI - Severe Coagulopathy after Ingestion of "Snake Wine". AB - BACKGROUND: This report describes a patient who developed coagulopathy after ingesting snake wine, which is an alcoholic libation containing an entire venomous snake. CASE REPORT: A 68-year-old man was admitted to the hospital 19 h after ingesting snake wine. The laboratory features upon admission included unmeasurable activated partial thromboplastin (aPTT) values, prolonged prothrombin time (PT) values, increased fibrinogen levels, modestly elevated fibrin degradation product and D-dimer values, uncorrected aPTT and PT values after a mixing test, and normal levels of aspartate transaminase and alanine transaminase. No pesticides, warfarin, or superwarfarin in the patient's blood or urine were detected. His coagulation profile normalized on the 6(th) day after admission after antivenom treatment. He was discharged 10 days later without sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The physician should be aware that ingesting snake wine may lead to systemic envenomation. As for coagulopathy, which may develop by ingesting snake venom, related laboratory findings may differ from the features observed after direct envenomation by snakebite. PMID- 26823134 TI - Blunt Chest Trauma Associated with Tension Pneumopericardium. PMID- 26823135 TI - Tracheal Tube Position Shift During Infant Resuscitation by Chest Compression: A Simulation Comparison by Fixation Method and With or Without Cuff. AB - BACKGROUND: Tracheal tube placement during infant resuscitation is essential for definite airway protection. Accidental extubation due to tracheal tube displacement is a rare event, but it results in severe complications, especially in infants. OBJECTIVE: The present study evaluated how infant tracheal tube displacement is affected by tape vs. tube holder fixation using a manikin. METHODS: A tracheal tube with internal diameter of 3.5 mm was placed 10 cm from the gum ridge in an advanced life support (ALS) Baby((r)) simulator (Laerdal, Stavanger, Norway). In the first trial, cuff pressure was set at 15, 20, and 25 cmH2O and trials were performed at each setting with no fixation, Durapore((r)) (3M, St Paul, MN) tape fixation, Multipore((r)) (3M) tape fixation, and Thomas((r)) Tube Holder (Laerdal) fixation. After 5 min of chest compression, the tracheal tube shift was measured. In the second trial, we compared the tube shift by chest compression with or without cuff in the same way. RESULTS: Relative to no fixation, tracheal tube shift was significantly less in the Durapore, Multipore, and tube holder groups (p < 0.05) at all cuff settings. Of the three fixation methods, the tube holder showed significantly less shift (p < 0.05) relative to tape, regardless of the initial cuff pressure. The positional shift after chest compressions was significantly larger in the trials with cuff than in those without cuff in Durapore or Multipore fixation (p < 0.05), but did not in tube holder fixation. CONCLUSIONS: There is less tracheal tube displacement with tube holder fixation than with tape during continuous infant chest compression simulation. The tube cuff can contribute to the positional shift of the tube during infant chest compression. PMID- 26823136 TI - The Emergency Medicine Workforce: Profile and Projections. AB - BACKGROUND: The landscape of the emergency medicine workforce has changed dramatically over the last few decades. The growth in emergency medicine residency programs has significantly increased the number of emergency medicine specialists now staffing emergency departments (EDs) throughout the country. Despite this increase in available providers, rising patient volumes, an aging population, ED overcrowding and inefficiency, increased regulation, and other factors have resulted in the continued need for additional emergency physicians. OBJECTIVES: To review current available data on patient volumes and characteristics, the overall physician workforce, the current emergency physician workforce, the impact of physician extenders and scribes on the practice of emergency medicine, and project emergency physician staffing needs into the future. DISCUSSION AND PROJECTIONS: We project that within the next 5 to 10 years, there will be enough board-certified or -eligible emergency physicians to provide care to all patients in the U.S. EDs. However, low-volume rural EDs will continue to have difficulty attracting emergency medicine specialists without significant incentives. CONCLUSIONS: There remains a shortage of board-certified emergency physicians, but it is decreasing every year. The use of physicians from other specialties to staff EDs has long been based on the theory that there is a long-standing shortage of available American Board of Emergency Medicine/American Osteopathic Board of Emergency Medicine physicians, both now and in the future. Our investigation shows that this is not supported by current data. Although there will always be regional and rural physician shortages, these are mirrored by all other specialties and are even more pressing in primary care. PMID- 26823137 TI - Effect of Volume of Fluid Resuscitation on Metabolic Normalization in Children Presenting in Diabetic Ketoacidosis: A Randomized Controlled Trial. AB - BACKGROUND: The optimal rate of fluid administration in pediatric diabetic ketoacidosis (DKA) is unknown. OBJECTIVE: Our aim was to determine whether the volume of fluid administration in children with DKA influences the rate of metabolic normalization. METHODS: We performed a randomized controlled trial conducted in a tertiary pediatric emergency department from December 2007 until June 2010. The primary outcome was time to metabolic normalization; secondary outcomes were time to bicarbonate normalization, pH normalization, overall length of hospital treatment, and adverse outcomes. Children between 0 and 18 years of age were eligible if they had type 1 diabetes mellitus and DKA. Patients were randomized to receive intravenous (IV) fluid at low volume (10 mL/kg bolus + 1.25 * maintenance rate) or high volume (20 mL/kg bolus + 1.5 * maintenance rate) (n = 25 in each). RESULTS: After adjusting for initial differences in bicarbonate levels, time to metabolic normalization was significantly faster in the higher volume infusion group compared to the low-volume infusion group (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.0-3.9; p = 0.04). Higher-volume IV fluid infusion appeared to hasten, to a greater extent, normalization of pH (HR = 2.5; 95% CI 1.2-5.0; p = 0.01) than normalization of serum bicarbonate (HR = 1.2; 95% CI 0.6-2.3; p = 0.6). The length of hospital treatment HR (0.8; 95% CI 0.4 1.5; p = 0.5) and time to discharge HR (0.8; 95% CI 0.4-1.5; p = 0.5) did not differ between treatment groups. CONCLUSIONS: Higher-volume fluid infusion in the treatment of pediatric DKA patients significantly shortened metabolic normalization time, but did not change overall length of hospital treatment. ClinicalTrials.gov ID NCT01701557. PMID- 26823138 TI - Clinical Guidelines for the Emergency Department Evaluation of Subarachnoid Hemorrhage. AB - BACKGROUND: Subarachnoid hemorrhage (SAH) is frequently caused by the rupture of an intracranial aneurysmal vessel or arteriovenous malformation, leading to a cascade of events that can result in severe disability or death. When evaluating for this diagnosis, emergency physicians have classically performed a noncontrast computed tomography (NCCT) scan, followed by a lumbar puncture (LP). Recently, however, as CT technology has advanced, many studies have questioned the necessity of the LP in the SAH diagnostic algorithm and have instead advocated for noninvasive techniques, such as NCCT alone or NCCT with CT angiogram (CTA). OBJECTIVE: The primary goal of this literature search was to determine the appropriate emergency department (ED) management of patients with suspected SAH. METHODS: A MEDLINE literature search from October 2008 to June 2015 was performed using the keywords computed tomography AND subarachnoid hemorrhage AND lumbar puncture, while limiting the search to human studies written in the English language. General review articles and single case reports were omitted. Each of the selected articles then underwent a structured review. RESULTS: Ninety-one articles were identified, with 31 papers being considered appropriate for analysis. These studies then underwent a rigorous review from which recommendations were developed. CONCLUSIONS: The literature search supports that NCCT followed by CTA is a reasonable approach in the evaluation of ED patients with possible SAH. PMID- 26823139 TI - Ectopic Pregnancy After Plan B Emergency Contraceptive Use. AB - BACKGROUND: Pregnancy outcomes after emergency contraceptive use has been debated over time, but review of the literature includes mechanisms by which these medications may increase the chance of an ectopic pregnancy. Such cases are infrequently reported, and many emergency providers may not readily consider this possibility when treating patients. CASE REPORT: This is a case presentation of ectopic pregnancy in a patient who had recently used Plan B (levonorgestrel) emergency contraceptive. She presented with abdominal pain and vaginal spotting, and was evaluated by serum testing and pelvic ultrasound. She was discovered to have a right adnexal pregnancy. She was treated initially with methotrexate, though she ultimately required surgery for definitive treatment. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case report aims to bring a unique clinical case to the attention of emergency providers. The goal is to review research on the topic of levonorgestrel use and the incidence of ectopic pregnancies. The mechanism of action of this emergency contraceptive is addressed, and though no definite causal relationship is known between levonorgestrel and ectopic pregnancies, there is a pharmacologic explanation for how this event may occur after use of this medication. Ultimately, the emergency provider will be reminded of the importance of educating the patient on the possible outcomes after its use, including failure of an emergency contraceptive and the potential of ectopic pregnancy. PMID- 26823140 TI - Assessing the toxicity of sediments using the medaka embryo-larval assay and 2 other bioassays. AB - Sediments are sinks for aquatic pollutants, and analyzing toxicity in such complex matrices is still challenging. To evaluate the toxicity of bioavailable pollutants accumulated in sediments from the Bizerte lagoon (Tunisia), a novel assay, the medaka embryo-larval assay by sediment contact, was applied. Japanese medaka (Oryzias latipes) embryos were incubated in direct contact with sediment samples up to hatching. Lethal and sublethal adverse effects were recorded in embryos and larvae up to 20 d postfertilization. Results from medaka embryo larval assay were compared with cytotoxicity (Microtox(r)), genotoxicity (SOS chromotest), and pollutant content of sediments. The results highlight differences in the contamination profile and toxicity pattern between the different studied sediments. A significant correlation was shown between medaka embryo-larval assay by sediment contact and SOS chromotest responses and concentrations of most organic pollutants studied. No correlation was shown between pollutant levels and Microtox. According to the number of sediment samples detected as toxic, medaka embryo-larval assay by sediment contact was more sensitive than Microtox, which in turn was more sensitive than the SOS chromotest; and medaka embryo-larval assay by sediment contact allowed sediment toxicity assessment of moderately polluted sediments without pollutant extraction and using an ecologically realistic exposure scenario. Although medaka embryo larval assay by sediment contact should be tested on a larger sample set, the results show that it is sensitive and convenient enough to monitor the toxicity of natural sediments. Environ Toxicol Chem 2016;35:2270-2280. (c) 2016 SETAC. PMID- 26823141 TI - Utility of Real-Time 3-Dimensional Transesophageal Echocardiography in the Assessment of Mitral Paravalvular Leak. AB - BACKGROUND: Mitral paravalvular leak (PVL) is a potential complication of surgical valve replacement procedures. Real-time 3D transesophageal echocardiography (RT-3DTEE) has emerged as an efficient tool for providing essential information about the anatomy of mitral PVLs compared with 2DTEE findings. The purpose of this study was to evaluate the utility of RT-3DTEE in the assessment of mitral PVLs. METHODS AND RESULTS: The 3D characteristics of PVLs were recorded and compared with 2D findings. We included 34 consecutive patients with clinical suspicion of mitral PVL in the study. Mitral PVLs were detected in 26 patients (76%); 26 PVLs were identified by 2DTEE and 37 by RT 3DTEE. Moderate or severe mitral regurgitation was present in 23 patients (88%). The most common PVL locations were the septal and posterior regions. The median PVL size measured by RT-3DTEE was 7 mm long*4 mm wide. The median vena contracta of defect measured by 2DTEE and RT-3DTEE was 5 mm and 4 mm, respectively. The median effective regurgitant orifice area of defect measured by RT-3DTEE was 0.36 cm(2). The defect types were "oval" (54%), "round" (35%), "crescentic" (8%) and highly irregular (3%). CONCLUSIONS: Compared with 2DTEE, RT-3DTEE provided detailed descriptions of the number, location, size and morphology of PVLs, which is essential for planning and guiding the potential corrective techniques. (Circ J 2016; 80: 738-744). PMID- 26823142 TI - Pediatric Cohort With Long QT Syndrome - KCNH2 Mutation Carriers Present Late Onset But Severe Symptoms. AB - BACKGROUND: In children with long QT syndrome (LQTS), risk factors for cardiac events have been reported, but age-, gender- and genotype-related differences in prognosis remain unknown in Asian countries. METHODS AND RESULTS: The study examined clinical prognosis at age between 1 and 20 years in 496 LQTS patients who were genotyped as either of LQT1-3 (male, n=206). Heterozygous mutations were observed in 3 major responsible genes:KCNQ1in271,KCNH2in 192, andSCN5Ain 33 patients. LQTS-associated events were classified into 3 categories: (1) syncope (n=133); (2) repetitive torsade de pointes (TdP, n=3); and (3) cardiopulmonary arrest (CPA, n=4). The risk of cardiac events was significantly lower in LQT1 girls than boys<=12 years (HR, 0.55), whereas LQT2 female patients >=13 years had the higher risk of cardiac events than male patients (HR, 4.60). Patients in the repetitive TdP or CPA group included 1 LQT1 female patient, 1 LQT2 male patient, and 5 LQT2 female patients. All LQT2 patients in these groups had TdP repeatedly immediately after the antecedent event. In addition, all 5 female LQT2 patients in these groups had the event after or near puberty. CONCLUSIONS: Female LQT2 children might have repeated TdP shortly after prior events, especially after puberty. (Circ J 2016; 80: 696-702). PMID- 26823143 TI - Elevated Red Blood Cell Distribution Width Predicts Recurrence After Catheter Ablation for Atrial Fibrillation in Patients With Heart Failure - Comparison With Non-Heart Failure Patients. AB - BACKGROUND: Elevated red blood cell distribution width (RDW) predicts poor prognosis in patients with cardiovascular diseases. However, little is known about the association between RDW and outcomes after catheter ablation of atrial fibrillation (AF). METHODS AND RESULTS: A total of 757 patients who underwent radiofrequency catheter ablation of AF were divided into heart failure (HF, n=79) and non-HF (n=678) groups; RDW was assessed as a predictor after catheter ablation in each. During a 22.3-month follow-up period, the baseline RDW in the HF group was greater in the recurrence group than in the non-recurrence group (14.5+/-2.0% vs. 13.5+/-0.9%, P=0.013). In contrast, no significant difference in RDW at baseline was found in the non-HF group between the recurrence and non recurrence groups (13.3+/-0.8% vs. 13.2+/-0.8%, P=0.332, respectively). Multivariate analysis demonstrated that RDW (hazard ratio 1.20, 95% confidence interval 1.01-1.40, P=0.034) was an independent predictor of AF recurrence in the HF group. The cut-off values of RDW for the recurrence of AF and major adverse events in the HF group were 13.9% and 14.8%, respectively. CONCLUSIONS: High RDW is an independent predictor for the recurrence of AF and major adverse events in patients with HF after catheter ablation. RDW is a potential noninvasive marker in AF patients complicated with HF. (Circ J 2016; 80: 627-638). PMID- 26823145 TI - Immediate closure of uterine wall following spontaneous rupture at 23 weeks' gestation, allowing prolongation of pregnancy. PMID- 26823144 TI - Aiolos collaborates with Blimp-1 to regulate the survival of multiple myeloma cells. AB - The transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1) has crucial roles in the control of plasma cell differentiation and in maintaining survival of plasma cells. However, how Blimp-1 ensures the survival of plasma cell malignancy, multiple myeloma (MM), has remained elusive. Here we identified Aiolos, an anti-apoptotic transcription factor of MM cells, as a Blimp 1-interacting protein by mass spectrometry. ChIP coupled with DNA microarray was used to profile the global binding of Aiolos and Blimp-1 to endogenous targets in MM cells, which revealed their co-binding to a large number of genes, including apoptosis-related genes. Accordingly, Blimp-1 and Aiolos regulate similar transcriptomes in MM cells. Analysis of the binding motifs for Blimp-1 and Aiolos uncovered a partial motif that was similar across sites for both proteins. Aiolos promotes the binding of Blimp-1 to target genes and thereby enhances Blimp-1 dependent transcriptional repression. Furthermore, treatment with an anti-MM agent, lenalidomide, caused ubiquitination and proteasomal degradation of Blimp 1, leading to the de-repression of a new Blimp-1 direct target, CULLIN 4A (CUL4A), and reduced Aiolos levels. Accordingly, lenalidomide-induced cell death was partially rescued by reintroduction of Blimp-1 or knockdown of CUL4A. Thus, we demonstrated the functional impacts and underlying mechanisms of the interaction between Aiolos and Blimp-1 in maintaining MM cell survival. We also showed that interruption of Blimp-1/Aiolos regulatory pathways contributes to lenalidomide-mediated anti-MM activity. PMID- 26823146 TI - Novel variants in ZNF34 and other brain-expressed transcription factors are shared among early-onset MDD relatives. AB - There are no known genetic variants with large effects on susceptibility to major depressive disorder (MDD). Although one proposed study approach is to increase sensitivity by increasing sample sizes, another is to focus on families with multiple affected individuals to identify genes with rare or novel variants with strong effects. Choosing the family-based approach, we performed whole-exome analysis on affected individuals (n = 12) across five MDD families, each with at least five affected individuals, early onset, and prepubertal diagnoses. We identified 67 genes where novel deleterious variants were shared among affected relatives. Gene ontology analysis shows that of these 67 genes, 18 encode transcriptional regulators, eight of which are expressed in the human brain, including four KRAB-A box-containing Zn(2+) finger repressors. One of these, ZNF34, has been reported as being associated with bipolar disorder and as differentially expressed in bipolar disorder patients compared to healthy controls. We found a novel variant-encoding a non-conservative P17R substitution in the conserved repressor domain of ZNF34 protein-segregating completely with MDD in all available individuals in the family in which it was discovered. Further analysis showed a common ZNF34 coding indel segregating with MDD in a separate family, possibly indicating the presence of an unobserved, linked, rare variant in that particular family. Our results indicate that genes encoding transcription factors expressed in the brain might be an important group of MDD candidate genes and that rare variants in ZNF34 might contribute to susceptibility to MDD and perhaps other affective disorders. PMID- 26823147 TI - Epilepsy: Does access to care influence the use of epilepsy surgery? PMID- 26823148 TI - Alzheimer disease: Cancer immunotherapy drug reduces symptoms of Alzheimer disease in mice. PMID- 26823149 TI - Multiple sclerosis in 2015: Managing the complexity of multiple sclerosis. PMID- 26823150 TI - Rare germline variant (rs78378222) in the TP53 3' UTR: Evidence for a new mechanism of cancer predisposition in Li-Fraumeni syndrome. AB - Germline mutations in TP53 are the underlying defects in Li-Fraumeni syndrome (LFS) and its variant, Li-Fraumeni-like (LFL) Syndrome, autosomal dominant disorders that are characterized by predisposition to multiple early onset cancers. Here, we identified rs78378222 (A > C), a rare variant that is located in the 3' untranslated region (3' UTR) of TP53, in 7 probands (5.4%) of a cohort from LFS/LFL patients without TP53 germline mutations in the coding regions. To support its association with the LFS/LFL phenotype, we assessed p53 expression in tumor specimens and fibroblasts from rs78378222[C] carriers. Additionally, we investigated using in silico tools the evolutionary conservation and whether rs78378222[C] affects microRNA (miRNA) binding sites in the 3' UTR of TP53 mRNA. We found lower p53 protein levels in biological samples from rs78378222[C] carriers. Additionally, we showed that rs78378222[C] could interfere with a putative target site of miR-545-3p, a novel miRNA that is predicted to directly target the 3' UTR TP53. To our knowledge, this is the first description of rs78378222[C] in LFS/LFL patients. Moreover, these findings suggest that rs78378222[C] lead to haploinsufficiency of p53, a new mechanism of carcinogenesis in LFS/LFL. PMID- 26823151 TI - Slowing and cooling of heavy or light (even with a tiny electric dipole moment) polar molecules using a novel, versatile electrostatic Stark decelerator. AB - To meet some demands for realizing precise measurements of an electric dipole moment of electron (eEDM) and examining cold collisions or cold chemical physics, we have proposed a novel, versatile electrostatic Stark decelerator with an array of true 3D electric potential wells, which are created by a series of horizontally-oriented, U-shaped electrodes with time-sequence controlling high voltages (+/- HV) and two guiding electrodes with a constant voltage. We have calculated the 2D electric field distribution, the Stark shifts of the four lowest rotational sub-levels of PbF molecules in the X1(2)Pi1/2(v = 0) electronic and vibrational ground states as well as the population in the different rotational levels. We have discussed the 2D longitudinal and transverse phase space acceptances of PbF molecules in our decelerator. Subsequently, we have simulated the dynamic processes of the decelerated PbF molecules using the 3D Monte-Carlo method, and have found that a supersonic PbF beam with a velocity of 300 m s(-1) can be efficiently slowed to about 5 m s(-1), which will greatly enhance the sensitivities to research a parity violation and measure an eEDM. In addition, we have investigated the dependences of the longitudinal velocity spread, longitudinal temperature and bunching efficiency on both the number of guiding stages and high voltages, and found that after bunching, a cold packet of PbF molecules in the J = 7/2, MOmega = -7/4 state with a longitudinal velocity spread of 0.69 m s(-1) (corresponding to a longitudinal temperature of 2.35 mK) will be produced by our high-efficient decelerator, which will generate a high energy-resolution molecular beam for studying cold collision physics. Finally, our novel decelerator can also be used to efficiently slow NO molecules with a tiny electric dipole moment (EDM) of 0.16 D from 315 m s(-1) to 28 m s(-1). It is clear that our proposed new decelerator has a good slowing performance and experimental feasibility as well as wide applications in the field of precise measurements and cold molecule physics. PMID- 26823153 TI - Enantioselective N-Heterocyclic Carbene Catalysis by the Umpolung of alpha,beta Unsaturated Ketones. AB - N-Heterocyclic carbene-catalyzed formation of beta-anionic intermediates from enones has been employed in the enantioselective synthesis of 2-aryl propionates. The reaction was achievable using a homochiral 4-MeOC6H4 morpholinone catalyst allowing the first example of enantioselective catalysis by umpolung of alpha,beta-unsaturated ketones. The reaction is high yielding, and shows robustness with reasonable generality. A mechanism is proposed in which the enantiodetermining protonation is achieved using either hexafluoroisopropanol or the formed naphthol product. PMID- 26823152 TI - Agreement between Medicare pharmacy claims, self-report, and medication inventory for assessing lipid-lowering medication use. AB - BACKGROUND: Medicare claims have been used to study lipid-lowering medication (LLM) use among US adults. METHODS: We analyzed the agreement between Medicare claims for LLM and LLM use indicated by self-report during a telephone interview and, separately, by a medication inventory performed during an in-home study visit upon enrollment into the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. We included REGARDS participants >=65 years enrolled in 2006-2007 with Medicare pharmacy benefits (Part D) from 120 days before their telephone interview through their medication inventory (n = 899). RESULTS: Overall, 39.2% and 39.5% of participants had a Medicare claim for an LLM within 120 days prior to their interview and medication inventory, respectively. Also, 42.7% of participants self-reported using LLMs, and 41.8% had an LLM in their medication inventory. The Kappa statistic (95% confidence interval [CI]) for agreement of Medicare claims with self-report and medication inventory was 0.68 (0.63-0.73) and 0.72 (0.68-0.77), respectively. No Medicare claims for LLMs were present for 22.1% (95%CI: 18.1-26.6%) of participants who self-reported taking LLMs and 18.9% (15.1-23.3%) with LLMs in their medication inventory. Agreement between Medicare claims and self-report was lower among Black male individuals (Kappa = 0.34 [95%CI: 0.14-0.54]) compared with Black female individuals (0.70 [0.61-0.79]), White male individuals (0.65 [0.56-0.75]), and White female individuals (0.79 [0.72-0.86]). Agreement between Medicare claims and the medication inventory was also low among Black male individuals (Kappa = 0.48 [95%CI: 0.29-0.66]). CONCLUSIONS: Although substantial agreement exists, many Medicare beneficiaries who self-report LLM use or have LLMs in a medication inventory have no claims for these medications. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26823154 TI - Dispersive Liquid-Liquid Microextraction Using Low-Toxic Solvent for the Determination of Heavy Metals in Water Samples by Inductively Coupled Plasma-Mass Spectrometry. AB - A low-toxic dispersive liquid-liquid microextraction (DLLME) combined with inductively coupled plasma-MS was used for preconcentration and determination of Cu, Cr, Cd, Ni, Mn, and Pb in real-water samples. In traditional DLLME analysis, chlorinated solvents have been widely used as extraction solvents. However, these solvents are not environmentally friendly. To overcome this problem, we used a low-toxic bromosolvent (1-bromo-3-methylbutane; lethal concentration, 50%, 6150 mg/kg) as the extraction solvent. To study the effects of different parameters on the extraction efficiency, an orthogonal array experimental design with an L16(4(5)) matrix was used. Under the best experimental conditions (i.e., concentration of complexing reagent 1-(2-pyridylazo)-2-naphthol, 1.5 * 10(-3) mol/L; pH, 7.0; volume of acetone, 0.5 mL; volume of 1-bromo-3 methylbutane, 30 MUL; and without salt addition), the enhancement factor ranged from 34 to 40. The linear dynamic range was 1-1000 MUg/L with r(2) values of 0.9984-0.9999, and the LODs were between 0.042 and 0.53 MUg/L. RSDs (at metal ion concentrations of 20 MUg/L, n = 6) were 2.12 to 3.42%. The developed method was successfully applied to the extraction and determination of the mentioned metal ions in real-water samples, and satisfactory results were obtained. PMID- 26823155 TI - Corrigendum: Epidemiology study of HBV genotypes and antiviral drug resistance in multi-ethnic regions from Western China. PMID- 26823156 TI - Using blocked fractional factorial designs to construct discrete choice experiments for healthcare studies. AB - Discrete choice experiments (DCEs) are increasingly used for studying and quantifying subjects preferences in a wide variety of healthcare applications. They provide a rich source of data to assess real-life decision-making processes, which involve trade-offs between desirable characteristics pertaining to health and healthcare and identification of key attributes affecting healthcare. The choice of the design for a DCE is critical because it determines which attributes' effects and their interactions are identifiable. We apply blocked fractional factorial designs to construct DCEs and address some identification issues by utilizing the known structure of blocked fractional factorial designs. Our design techniques can be applied to several situations including DCEs where attributes have different number of levels. We demonstrate our design methodology using two healthcare studies to evaluate (i) asthma patients' preferences for symptom-based outcome measures and (ii) patient preference for breast screening services. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26823157 TI - Active Morphology Control for Concomitant Long Distance Spin Transport and Photoresponse in a Single Organic Device. AB - Long distance spin transport and photoresponse are demonstrated in a single F16 CuPc spin valve. By introducing a low-temperature strategy for controlling the morphology of the organic layer during the fabrication of a molecular spin valve, a large spin-diffusion length up to 180 nm is achieved at room temperature. Magnetoresistive and photoresponsive signals are simultaneously observed even in an air atmosphere. PMID- 26823158 TI - [Usefulness of biomarkers in the prognosis of severe head injuries]. AB - Severe head injuries have a great socioeconomic and public health impact. Despite progress in diagnosis and treatment, no sufficiently reliable predictive models have been established for developing clinical trials and promoting effective therapeutic strategies capable of improving the prognosis. In the last decades, several brain damage biomarkers have been studied as potential diagnostic and prognostic tools in traumatic brain injury. However, all of them have limitations that preclude their universalized application. The properties of the known biomarkers -both those traditionally shown to correlate with severity and prognosis, and those recently announced as promising options- should be analyzed. New studies are needed to define their properties, both isolatedly and in combined use. PMID- 26823159 TI - Efficient computational simulation of actin stress fiber remodeling. AB - Understanding collagen and stress fiber remodeling is essential for the development of engineered tissues with good functionality. These processes are complex, highly interrelated, and occur over different time scales. As a result, excessive computational costs are required to computationally predict the final organization of these fibers in response to dynamic mechanical conditions. In this study, an analytical approximation of a stress fiber remodeling evolution law was derived. A comparison of the developed technique with the direct numerical integration of the evolution law showed relatively small differences in results, and the proposed method is one to two orders of magnitude faster. PMID- 26823160 TI - Extracorporeal antimicrobial elimination enables antimicrobial mixing and affects resident bacteria. PMID- 26823161 TI - Regional climate change scenarios applied to viticultural zoning in Mendoza, Argentina. AB - Due to the importance of the winemaking sector in Mendoza, Argentina, the assessment of future scenarios for viticulture is of foremost relevance. In this context, it is important to understand how temperature increase and precipitation changes will impact on grapes, because of changes in grapevine phenology and suitability wine-growing regions must be understood as an indicator of climate change. The general objective is to classify the suitable areas of viticulture in Argentina for the current and future climate using the MM5 regional climate change simulations. The spatial distribution of annual mean temperature, annual rainfall, and some bioclimatic indices has been analyzed for the present (1970 1989) and future (2080-2099) climate under SRES A2 emission scenario. In general, according to projected average growing season temperature and Winkler index classification, the regional model estimates (i) a reduction of cool areas, (ii) a westward and southward displacement of intermediate and warm suitability areas, and (iii) the arise of new suitability regions (hot and very hot areas) over Argentina. In addition, an increase of annual accumulated precipitation is projected over the center-west of Argentina. Similar pattern of change is modeled for growing season, but with lower intensity. Furthermore, the evaluation of projected seasonal precipitation shows a little precipitation increase over Cuyo and center of Argentina in summer and a little precipitation decrease over Cuyo and northern Patagonia in winter. Results show that Argentina has a great potential for expansion into new suitable vineyard areas by the end of twenty first century, particularly due to projected displacement to higher latitudes for most present suitability winegrowing regions. Even though main conclusions are based on one global-regional model downscaling, this approach provides valuable information for implementing proper and diverse adaptation measures in the Argentinean viticultural regions. It has been concluded that regional climate change simulations are an adequate methodology, and indeed, the MM5 regional model is an appropriate tool to be applied in viticultural zoning in Mendoza, Argentina. PMID- 26823162 TI - The Measurement of Protein in Powdered Milk Products and Infant Formulas: A Review and Recent Developments. AB - Proteins are a key nutritional component of both powdered milk and infant formula types of product, and reliable methods for their determination are important for manufacturing and international trade. In this review, we distinguish between methods used for determining protein quality for nutrition purposes and those used for determining chemically defined protein. The former methods cover the ability of a dietary protein source to meet human nutritional requirements for the indispensable amino acids. The latter are chemical methods for the determination of total protein and can be divided into three broad types: total nitrogen determination, direct protein determination, and indirect protein determination. Current techniques and recent developments in each are reviewed. PMID- 26823163 TI - General Mathematical Ability Predicts PASAT Performance in MS Patients: Implications for Clinical Interpretation and Cognitive Reserve. AB - OBJECTIVES: The Paced Auditory Serial Addition Test (PASAT) is used to assess cognitive status in multiple sclerosis (MS). Although the mathematical demands of the PASAT seem minor (single-digit arithmetic), cognitive psychology research links greater mathematical ability (e.g., algebra, calculus) to more rapid retrieval of single-digit math facts (e.g., 5+6=11). The present study evaluated the hypotheses that (a) mathematical ability is related to PASAT performance and (b) both the relationship between intelligence and PASAT performance as well as the relationship between education and PASAT performance are both mediated by mathematical ability. METHODS: Forty-five MS patients were assessed using the Wechsler Test of Adult Reading, PASAT and Calculation Subtest of the Woodcock Johnson-III. Regression based path analysis and bootstrapping were used to compute 95% confidence intervals and test for mediation. RESULTS: Mathematical ability (a) was related to PASAT (beta=.61; p<.001) and (b) fully mediated the relationship between Intelligence and PASAT (beta=.76; 95% confidence interval (CI95)=.28, 1.45; direct effect of Intelligence, beta=.42; CI95=-.39, 1.23) as well as the relationship between Education and PASAT (beta=2.43, CI95=.81, 5.16, direct effect of Education, beta=.83, CI95=-1.95, 3.61). DISCUSSION: Mathematical ability represents a source of error in the clinical interpretation of cognitive decline using the PASAT. Domain-specific cognitive reserve is discussed. PMID- 26823164 TI - Variability in length of stay after uncomplicated pulmonary lobectomy: is length of stay a quality metric or a patient metric??. AB - OBJECTIVES: Previous studies have identified predictors of prolonged length of stay (LOS) following pulmonary lobectomy. LOS is typically described to have a direct relationship to postoperative complications. We sought to determine the LOS and factors associated with variability after uncomplicated pulmonary lobectomy. METHODS: Analysing the State Inpatient Databases, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality database, we reviewed lobectomies performed (2009-11) on patients in California, Florida and New York. LOS and comorbidities were identified. Multivariable regression analysis (MVA) was used to determine factors associated with LOS greater than the median. Patients with postoperative complications or death were excluded. RESULTS: Among 22 647 lobectomies performed, we identified 13 099 patients (58%) with uncomplicated postoperative courses (mean age = 66 years; 56% female; 76% white, 57% Medicare; median DEYO comorbidity score = 3, 55% thoracotomy, 45% thoracoscopy/robotic). There was a wide distribution in LOS [median LOS = 5 days; interquartile range (IQR) 4-7]. By MVA, predictors of prolonged LOS included, age >= 75 years [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.4-2.0], male gender (OR 1.2, 95% CI 1.1-1.2), chronic obstructive pulmonary disease (OR 1.6, 95% CI 1.5-1.7) and other comorbidities, Medicaid payer (OR 1.7, 95% CI 1.4-2.1) versus private insurance, thoracotomy (OR 3.0, 95% CI 2.8-3.3) versus video assisted thoracoscopic surgery/robotic approach and low hospital volume (OR 2.4, 95% CI 2.1-2.6). CONCLUSIONS: Variability exists in LOS following even uncomplicated pulmonary lobectomy. Variability is driven by clinical factors such as age, gender, payer and comorbidities, but also by surgical approach and volume. All of these factors should be taken into account when designing clinical care pathways or when allocating payment resources. Attempts to define an optimal LOS depend heavily upon the patient population studied. PMID- 26823165 TI - Minimally invasive approach for aortic arch surgery employing the frozen elephant trunk technique. AB - OBJECTIVES: Classically, repair of extensive thoracic aortic pathologies including the aortic arch and descending aorta required two separate major surgical procedures via full sternotomy and a subsequent left lateral thoracotomy. We describe herein our preliminary institutional experience with minimally invasive single-stage extended thoracic aortic replacement employing the frozen elephant trunk (FET) technique via partial upper sternotomy (PUS) in 14 patients. METHODS: Between December 2013 and January 2015, 14 consecutive patients with elective indications for FET underwent minimally invasive FET via PUS (PUS-FET) during moderate systemic hypothermia (28 degrees C) and selective antegrade cerebral perfusion (ACP) using the E-vita Open(r) hybrid prosthesis (Jotec GmbH, Hechingen, Germany). The patients' mean age was 66 +/- 6 years, and 9 patients (64%) were male. The arch vessels were reimplanted en bloc in all patients. Clinical data were prospectively entered into our institutional database. RESULTS: The surgical procedure was successful in all patients with no need for conversion to full sternotomy. An additional David procedure was performed in 1 patient, whereas 2 patients received a concomitant Bentall procedure. There was no perioperative death or 30-day mortality. The mean cardiopulmonary bypass time was 214 +/- 35 min, and the myocardial ischaemic time was 125 +/- 14 min. The ACP time was 54 +/- 9 min, whereas the ventilation time reached 11 +/- 4 h. Intensive care unit stay was 2 +/- 3 days. Chest tube drainage within the first 24 h was 460 +/- 130 ml. None of the 14 patients required re-exploration for bleeding. Patients were discharged after a hospital length of stay of 9 +/- 2 days. No postoperative permanent neurological complication occurred. Two patients (14%) experienced temporary delirium with complete resolution of symptoms prior to discharge from the hospital. CONCLUSIONS: Our preliminary experience suggests that minimally invasive single stage extended thoracic aortic replacement can safely and reproducibly be performed by employing the concept of PUS-FET. PMID- 26823166 TI - Re: Minimally invasive approach for aortic arch surgery employing the frozen elephant trunk technique. PMID- 26823167 TI - Ordered self-assembly of the collagenous domain of adiponectin with noncovalent interactions via glycosylated lysine residues. AB - Adiponectin, an anti-atherogenic and insulin-sensitizing adipokine, forms multiple isoforms including a trimer, a hexamer and heavier oligomers (mainly octadecamer) that determine their biological activities. We designed 89-residue peptides containing modifications found in the collagenous domain of native adiponectin. Circular dichroism and analytical ultracentrifugation measurements showed that the peptide bearing glucosyl-galactosyl-hydroxylysine residues forms a stable collagen-like triple helical structure and spontaneously assembled into an octadecamer. An assembly model mediated by noncovalent interactions via glycosylated lysine residues for the octadecamer was constructed. Our findings clarified an essential role of glycosyl modifications to coordinate the ordered self-assembly of adiponectin. PMID- 26823168 TI - Thermal and chemical unfolding pathways of PaSdsA1 sulfatase, a homo-dimer with topologically interlinked chains. AB - Understanding the mechanisms as to how interlinked proteins entangle and fold is a challenge. PaSdsA1 sulfatase is a homo-dimer containing two zinc atoms per monomer. The monomer chains are interlinked in a dimerization domain. To study the unfolding pathways denaturation experiments were performed. In the native protein three forms coexist in chemical equilibrium, each with a different number of zinc atoms. In the chemical unfolding of the holo-dimers the entanglement of the chains is preserved and acts as a 'folding seed', allowing the unfolding process to be reversible. Thermal irreversible unfolding of the holo-dimers favours dissociation, producing monomers that are SDS-stabilized. The thermal unfolding of these monomers is reversible. However, it is not possible to form dimers from unfolded monomers. PMID- 26823169 TI - The outer membrane porin OmpW of Acinetobacter baumannii is involved in iron uptake and colistin binding. AB - This study was undertaken to characterize functions of the outer membrane protein OmpW, which potentially contributes to the development of colistin- and imipenem resistance in Acinetobacter baumannii. Reconstitution of OmpW in artificial lipid bilayers showed that it forms small channels (23 pS in 1 m KCl) and markedly interacts with iron and colistin, but not with imipenem. In vivo, (55) Fe uptake assays comparing the behaviours of DeltaompW mutant and wild-type strains confirmed a role for OmpW in A. baumannii iron homeostasis. However, the loss of OmpW expression did not have an impact on A. baumannii susceptibilities to colistin or imipenem. PMID- 26823170 TI - Host-parasite interaction: multiple sites in the Plasmodium vivax tryptophan-rich antigen PvTRAg38 interact with the erythrocyte receptor band 3. AB - Tryptophan-rich antigens of malarial parasites interact with host molecules and play an important role in parasite survival. Merozoite expressed Plasmodium vivax tryptophan-rich antigen PvTRAg38 binds to human erythrocytes and facilitates parasite growth in a heterlologous Plasmodium falciparum culture system. Recently, we identified band 3 in human erythrocytes as one of its receptors, although the receptor-ligand binding mechanisms remain unknown. In the present study, using synthetic mutated peptides of PvTRAg38, we show that multiple amino acid residues of its 12 amino acid domain (KWVQWKNDKIRS) at position 197-208 interact with three different ectodomains of band 3 receptor on human erythrocytes. Our findings may help in the design of new therapeutic approaches for malaria. PMID- 26823171 TI - Quantifying the magnitude of the oxygen artefact inherent in culturing airway cells under atmospheric oxygen versus physiological levels. AB - To date, in vitro studies assessing the pulmonary toxicity of inhaled particles have provided poor correlation with in vivo results. We explored whether this discrepancy reflected cellular adaptations in pulmonary cells cultured under atmospheric oxygen concentrations (21%) compared with in vivo alveolar concentrations (100 mm Hg, ~ 13%) and whether this blunted cellular responses to nanoparticle challenge. At 21% oxygen, A549 cells had augmented intracellular glutathione concentrations, with evidence of increased tolerance to CuO nanoparticles, with reduced reactive oxygen species production, blunted transcriptional responses and delayed cell death, compared to cells cultured at 13% oxygen. These data support the contention that standard cell culture conditions pre-adapt cells to oxidative insults and emphasize the necessity of ensuring normoxic conditions in model systems to improve their predictive value. PMID- 26823172 TI - The potential role of regulator of G-protein signaling 16 in cell motility mediated by deltaEF1 family proteins. AB - The epithelial-mesenchymal transition (EMT) is associated with tumor progression. We reported previously that expression of the deltaEF1 family proteins (deltaEF1/ZEB1 and SIP1/ZEB2), key regulators of the EMT, is positively correlated with EMT phenotypes and aggressiveness of breast cancer. Here, we show that the expression levels of regulator of G-protein signaling 16 (RGS16) are negatively correlated with those of the deltaEF1 family proteins. On the basis of the results of gain- and loss-of-function analyses, we suggest that deltaEF1 family proteins promote cell motility of breast cancer cells directly or indirectly through repressing expression of RGS16. PMID- 26823173 TI - Activation of the cAMP/protein kinase A signalling pathway by coronin 1 is regulated by cyclin-dependent kinase 5 activity. AB - Coronins constitute a family of conserved proteins expressed in all eukaryotes that have been implicated in the regulation of a wide variety of cellular activities. Recent work showed an essential role for coronin 1 in the modulation of the cAMP/PKA pathway in neurons through the interaction of coronin 1 with the G protein subtype Galphas in a stimulus-dependent manner, but the molecular mechanism regulating coronin 1-Galphas interaction remains unclear. We here show that phosphorylation of coronin 1 on Thr(418/424) by cyclin-dependent kinase (CDK) 5 activity was responsible for coronin 1-Galphas association and the modulation of cAMP production. Together these results show an essential role for CDK5 activity in promoting the coronin 1-dependent cAMP/PKA pathway. PMID- 26823174 TI - Crystal structures of penicillin-binding protein 3 in complexes with azlocillin and cefoperazone in both acylated and deacylated forms. AB - Penicillin-binding protein 3 (PBP3) from Pseudomonas aeruginosa is the molecular target of beta-lactam-based antibiotics. Structures of PBP3 in complexes with azlocillin and cefoperazone, which are in clinical use for the treatment of pseudomonad infections, have been determined to 2.0 A resolution. Together with data from other complexes, these structures identify a common set of residues involved in the binding of beta-lactams to PBP3. Comparison of wild-type and an active site mutant (S294A) showed that increased thermal stability of PBP3 following azlocillin binding was entirely due to covalent binding to S294, whereas cefoperazone binding produces some increase in stability without the covalent link. Consistent with this, a third crystal structure was determined in which the hydrolysis product of cefoperazone was noncovalently bound in the active site of PBP3. This is the first structure of a complex between a penicillin-binding protein and cephalosporic acid and may be important in the design of new noncovalent PBP3 inhibitors. PMID- 26823175 TI - Crystal structures of chitin binding domains of chitinase from Thermococcus kodakarensis KOD1. AB - Chitinase from T. kodakarensis (TkChiA) catalyzes the hydrolysis of chitin. The enzyme consists of two catalytic and three binding domains (ChBD1, ChBD2 and ChBD3). ChBD2 and ChBD3 can bind to not only chitin but also cellulose. In both domains, the intervals of the side chains of the three tryptophan residues, which are located on the molecular surface, correspond to twice the length of the lattice of the chitin. A binding model with crystalline chitin implies that the tryptophan residues and a glutamate residue interact with the hexose ring by CH pi interactions and the amide group by a hydrogen bond, respectively. PMID- 26823176 TI - Scalable Total Synthesis of rac-Jungermannenones B and C. AB - Reported is the first scalable synthesis of rac-jungermannenones B and C starting from the commercially available and inexpensive geraniol in 10 and 9 steps, respectively. The unique jungermannenone framework is rapidly assembled by an unprecedented regioselective 1,6-dienyne reductive cyclization reaction which proceeds through a vinyl radical cyclization/allylic radical isomerization mechanism. DFT calculations explain the high regioselectivity observed in the 1,6 dienyne reductive radical cyclization. PMID- 26823177 TI - Effect of the adjuvanted (AS03) A/H1N1 2009 pandemic influenza vaccine on the risk of rejection in solid organ transplant recipients in England: a self controlled case series. AB - OBJECTIVE: To assess the risk of solid organ transplant (SOT) rejection after vaccination with the adjuvanted (AS03) A/H1N1 2009 pandemic influenza vaccine Pandemrix. DESIGN: Self-controlled case series (SCCS) in the UK Clinical Practice Research Datalink (CPRD) and its linked component of the Hospital Episodes Statistics (HES) inpatient database. Analyses were conducted using the SCCS method for censored, perturbed or curtailed post-event exposure. PARTICIPANTS: Of the 184 transplant recipients having experienced at least one SOT rejection (liver, kidney, lung, heart or pancreas) during the study period from 1 October 2009 to 31 October 2010, 91 participants were included in the main analysis, of which 71 had been exposed to Pandemrix. MAIN OUTCOME MEASURES: Occurrence of SOT rejection during risk (30 and 60 days after any Pandemrix dose) and control periods. Covariates in the CPRD included time since transplantation, seasonal influenza vaccination, bacterial and viral infections, previous SOT rejections and malignancies. RESULTS: The relative incidence (RI) of rejection of any one of the five transplanted organs, adjusted for time since transplantation, was 1.05 (95% CI 0.52 to 2.14) and 0.80 (95% CI 0.42 to 1.50) within 30 and 60 days after vaccination, respectively. Similar estimates were observed for rejection of a kidney only, the most commonly transplanted organ (RI within 30 days after vaccination: 0.85 (95% CI 0.38 to 1.90)). Across various models and sensitivity analyses, RI estimates remained stable and within a consistent range around 1.0. CONCLUSIONS: These results suggest a reassuring safety profile for Pandemrix with regard to the risk of rejection in SOT recipients in England and contribute to inform the benefit-risk of AS03-adjuvanted pandemic influenza vaccines in transplanted patients in the event of future pandemics. TRIAL REGISTRATION NUMBER: NCT01715792. PMID- 26823178 TI - Financial accessibility and user fee reforms for maternal healthcare in five sub Saharan countries: a quasi-experimental analysis. AB - OBJECTIVES: Evidence on whether removing fees benefits the poorest is patchy and weak. The aim of this paper is to measure the impact of user fee reforms on the probability of giving birth in an institution or undergoing a caesarean section (CS) in Ghana, Burkina Faso, Zambia, Cameroon and Nigeria for the poorest strata of the population. SETTING: Women's experience of user fees in 5 African countries. PRIMARY AND SECONDARY OUTCOME MEASURES: Using quasi-experimental regression analysis we tested the impact of user fee reforms on facilities' births and CS differentiated by wealth, education and residence in Burkina Faso and Ghana. Mapping of the literature followed by key informant interviews are used to verify details of reform implementation and to confirm and support our countries' choice. PARTICIPANTS: We analysed data from consecutive surveys in 5 countries: 2 case countries that experienced reforms (Ghana and Burkina Faso) by contrast with 3 that did not experience reforms (Zambia, Cameroon, Nigeria). RESULTS: User fee reforms are associated with a significant percentage of the increase in access to facility births (27 percentage points) and to a much lesser extent to CS (0.7 percentage points). Poor (but not the poorest), and non educated women, and those in rural areas benefitted the most from the reforms. User fees reforms have had a higher impact in Burkina Faso compared with Ghana. CONCLUSIONS: Findings show a clear positive impact on access when user fees are removed, but limited evidence for improved availability of CS for those most in need. More women from rural areas and from lower socioeconomic backgrounds give birth in health facilities after fee reform. Speed and quality of implementation might be the key reason behind the differences between the 2 case countries. This calls for more research into the impact of reforms on quality of care. PMID- 26823179 TI - Effectiveness, safety and costs of thromboembolic prevention in patients with non valvular atrial fibrillation: phase I ESC-FA protocol study and baseline characteristics of a cohort from a primary care electronic database. AB - PURPOSE: Atrial fibrillation is the most common arrhythmia. Its management aims to reduce symptoms and to prevent complications through rate and rhythm control, management of concomitant cardiac diseases and prevention of related complications, mainly stroke. The main objective of Effectiveness, Safety and Costs in Atrial Fibrillation (ESC-FA) study is to analyse the drugs used for the management of the disease in real-use conditions, particularly the antithrombotic agents for stroke prevention. The aim of this work is to present the study protocol of phase I of the ESC-FA study and the baseline characteristics of newly diagnosed patients with atrial fibrillation in Catalonia, Spain. PARTICIPANTS: The data source is System for the Improvement of Research in Primary Care (SIDIAP) database. The population included are all patients with non-valvular atrial fibrillation diagnosis registered in the electronic health records during 2007-2012. FINDINGS TO DATE: A total of 22,585 patients with non-valvular atrial fibrillation were included in the baseline description. Their mean age was 72.8 years and 51.6% were men. The most commonly prescribed antithrombotics were vitamin K antagonists (40.1% of patients) and platelet aggregation inhibitors (32.9%); 25.3% had not been prescribed antithrombotic treatment. Age, gender, comorbidities and co-medication at baseline were similar to those reported for previous studies. FUTURE PLANS: The next phase in the ESC-FA study will involve assessing the effectiveness and safety of antithrombotic treatments, analysing stroke events and bleeding episodes' rates in our patients (rest of phase I), describing the current management of the disease and its costs in our setting, and assessing how the introduction of new oral anticoagulants changes the stroke prevention in non-valvular atrial fibrillation. PMID- 26823180 TI - Chinese Obstetrics & Gynecology journal club: a randomised controlled trial. AB - OBJECTIVES: To assess whether a journal club model could improve comprehension and written and spoken medical English in a population of Chinese medical professionals. SETTING AND PARTICIPANTS: The study population consisted of 52 medical professionals who were residents or postgraduate master or PhD students in the Department of Obstetrics and Gynecology, Heilongjiang University of Chinese Medicine, China. INTERVENTION: After a three-part baseline examination to assess medical English comprehension, participants were randomised to either (1) an intensive journal club treatment arm or (2) a self-study group. At the conclusion of the 8-week intervention participants (n=52) were re-tested with new questions. OUTCOME MEASURES: The primary outcome was the change in score on a multiple choice examination. Secondary outcomes included change in scores on written and oral examinations which were modelled on the Test of English as a Foreign Language (TOEFL). RESULTS: Both groups had improved scores on the multiple choice examination without a statistically significant difference between them (90% power). However, there was a statistically significant difference between the groups in mean improvement in scores for both written (95% CI 1.1 to 5.0; p=0.003) and spoken English (95% CI 0.06 to 3.7; p=0.04) favouring the journal club intervention. CONCLUSIONS: Interacting with colleagues and an English-speaking facilitator in a journal club improved both written and spoken medical English in Chinese medical professionals. Journal clubs may be suitable for use as a self-sustainable teaching model to improve fluency in medical English in foreign medical professionals. TRIAL REGISTRATION NUMBER: NCT01844609. PMID- 26823181 TI - Injury Profile in Swedish Elite Floorball. AB - BACKGROUND: Floorball is an indoor team sport with growing popularity worldwide characterized by rapid accelerations, decelerations, and cutting and pivoting movements. While injuries are common, there are few high-quality epidemiological investigations of floorball injuries. Therefore, the aim of this study was to determine the incidence and severity of injuries in male and female elite-level floorball players in Sweden. HYPOTHESIS: The incidence of injuries has not decreased; female players are more vulnerable to injury than male players. STUDY DESIGN: Prospective cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: Twelve floorball teams (6 male, 6 female) in the Swedish premiere leagues were followed for 1 year (preseason, game season, and the entire year). The team medical staff reported injury incidence, location, type (traumatic or overuse), and severity. Differences between male and female players were analyzed using the Mann-Whitney U test. RESULTS: The injury incidence was greater in female players during preseason (22.9 vs 7.4, P = 0.01), game season (39.5 vs 28.3, P = 0.002), as well as the whole year combined (33.9 vs 20.8, P = 0.02). The thigh was the most common injury location in male players and the ankle in female players. Overuse injuries were more common among men and were primarily back problems. Traumatic injuries were more common in women-mainly knee and ankle injuries. Most injuries were of mild severity. A greater number of anterior cruciate ligament injuries occurred in women (n = 11) than in men (n = 2). CONCLUSION: The injury incidence was significantly greater in female floorball players throughout the entire floorball year. Male players sustained mostly overuse injuries while female players suffered traumatic injuries. The majority of injuries in floorball were mild, irrespective of player sex. CLINICAL RELEVANCE: Knowledge of the incidence and severity of floorball injuries is an essential step in the sequence of injury prevention. Future research should focus on identifying injury mechanisms and risk factors for these injuries to develop injury prevention strategies. PMID- 26823182 TI - Anemia and risk for cognitive decline in chronic kidney disease. AB - BACKGROUND: Anemia is common among patients with chronic kidney disease (CKD) but its health consequences are poorly defined. The aim of this study was to determine the relationship between anemia and cognitive decline in older adults with CKD. METHODS: We studied a subgroup of 762 adults age >=55 years with CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) study. Anemia was defined according to the World Health Organization criteria (hemoglobin <13 g/dL for men and <12 g/dL for women). Cognitive function was assessed annually with a battery of six tests. We used logistic regression to determine the association between anemia and baseline cognitive impairment on each test, defined as a cognitive score more than one standard deviation from the mean, and mixed effects models to determine the relation between anemia and change in cognitive function during follow-up after adjustment for demographic and clinical characteristics. RESULTS: Of 762 participants with mean estimated glomerular filtration rate of 42.7 +/- 16.4 ml/min/1.73 m(2), 349 (46 %) had anemia. Anemia was not independently associated with baseline cognitive impairment on any test after adjustment for demographic and clinical characteristics. Over a median 2.9 (IQR 2.6-3.0) years of follow-up, there was no independent association between anemia and change in cognitive function on any of the six cognitive tests. CONCLUSIONS: Among older adults with CKD, anemia was not independently associated with baseline cognitive function or decline. PMID- 26823183 TI - Shifting from control to elimination: analysis of malaria epidemiological characteristics in Tengchong County around China-Myanmar border, 2005-2014. AB - BACKGROUND: Tengchong County experienced a decreasing malaria prevalence period in 2005-2014 but the factors contributing to the trend are unclear. Herein, the malaria epidemiological data in years of 2005-2014 were collected and analysed, in order to provide evidence for subsequent effective strategic planning of malaria elimination that may be referenced by other counties with the similar elimination programmes along the China-Myanmar border. METHODS: A retrospective study was conducted to explore malaria-endemic characteristics in years 2005-2014 in Tengchong County. All individual cases from a web-based reporting system were reviewed and analysed. Local infections and imported cases were obtained from an annual reporting system. RESULTS: In total, 8321 confirmed malaria cases were recorded in this period, and 91.5% of them were reported during 2005-2010. Plasmodium vivax was the major species (n = 5867, 70.5%). Most cases (92.9%) were found in males, mainly in the age group 30-34 years. Only five deaths resulting from Plasmodium falciparum were reported, of which three occurred in 2005. The cases were mainly reported in the townships of Wuhe (18.5%), Mangbang (12.8%) and Gudong (9.3%). In addition, 147 local malaria (1.8%) and 8174 imported malaria (98.2%) were observed during 2005-2014. However, the proportion of imported malaria was more than 95% all the time and no local transmission has been observed since 2013. Moreover, Myanmar was the main imported source, with 716 cases (94.6%, 716/757) from Myanmar in 2011-2014. CONCLUSIONS: Tengchong County has made achievements in controlling malaria, with incidence at historically its lowest level. However, imported malaria has increased and poses a great threat to malaria elimination. To achieve the elimination goal and prevent the re introduction of malaria, surveillance systems need to be well planned and managed to ensure timely case detection and prompt response targeted to the mobile and migrate population at elimination stage. PMID- 26823184 TI - Bacteriophages affect evolution of bacterial communities in spatially distributed habitats: a simulation study. AB - BACKGROUND: Bacteriophages are known to be one of the driving forces of bacterial evolution. Besides promoting horizontal transfer of genes between cells, they may induce directional selection of cells (for instance, according to more or less resistance to phage infection). Switching between lysogenic and lytic pathways results in various types of (co)evolution in host-phage systems. Spatial (more generally, ecological) organization of the living environment is another factor affecting evolution. In this study, we have simulated and analyzed a series of computer models of microbial communities evolving in spatially distributed environments under the pressure of phage infection. RESULTS: We modeled evolving microbial communities living in spatially distributed flowing environments. Non specific nutrient supplied in the only spatial direction, resulting in its non uniform distribution in environment. We varied the time and the location of initial phage infestation of cells as well as switched chemotaxis on and off. Simulations were performed with the Haploid evolutionary constructor software ( http://evol-constructor.bionet.nsc.ru/ ). CONCLUSION: Simulations have shown that the spatial location of initial phage invasion may lead to different evolutionary scenarios. Phage infection decreases the speciation rate by more than one order as far as intensified selection blocks the origin of novel viable populations/species, which could carve out potential ecological niches. The dependence of speciation rate on the invasion node location varied on the time of invasion. Speciation rate was found to be lower when the phage invaded fully formed community of sedentary cells (at middle and late times) at the species rich regions. This is especially noticeable in the case of late-time invasion. Our simulation study has shown that phage infection affects evolution of microbial community slowing down speciation and stabilizing the system as a whole. This influencing varied in its efficiency depending on spatially ecological factors as well as community state at the moment of phage invasion. PMID- 26823186 TI - Influenza-binding sialylated polymer coated gold nanoparticles prepared via RAFT polymerization and reductive amination. AB - We report on a straightforward strategy to fabricate bioactive glycosylated gold nanoparticles via a combination of RAFT polymerization, carbohydrate ligation through reductive amination and thiol-gold self-assembly. This approach is used for the design of gold nanoparticles decorated with the complex sialylated glycan Neu5Ac-alpha-2-6-Gal, and we demonstrate multivalent and specific recognition between the nanoparticles, lectins and hemagglutinin on the surface of the influenza virus. PMID- 26823185 TI - The evaluation and application of multilocus variable number tandem repeat analysis (MLVA) for the molecular epidemiological study of Salmonella enterica subsp. enterica serovar Enteritidis infection. AB - BACKGROUND: Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis) is one of the most prevalent Salmonella serotypes that cause gastroenteritis worldwide and the most prevalent serotype causing Salmonella infections in China. A rapid molecular typing method with high throughput and good epidemiological discrimination is urgently needed for detecting the outbreaks and finding the source for effective control of S. Enteritidis infections. METHODS: In this study, 194 strains which included 47 from six outbreaks that were well-characterized epidemiologically were analyzed with pulse field gel electrophoresis (PFGE) and multilocus variable number tandem repeat analysis (MLVA). Seven VNTR loci published by the US Center for Disease Control and Prevention (CDC) were used to evaluate and develop MLVA scheme for S. Enteritidis molecular subtyping by comparing with PFGE, and then MLVA was applied to the suspected outbreaks detection. All S. Enteritidis isolates were analyzed with MLVA to establish a MLVA database in Shenzhen, Guangdong province, China to facilitate the detection of S. Enteritidis infection clusters. RESULTS: There were 33 MLVA types and 29 PFGE patterns among 147 sporadic isolates. These two measures had Simpson indices of 0.7701 and 0.8043, respectively, which did not differ significantly. Epidemiological concordance was evaluated by typing 47 isolates from six epidemiologically well-characterized outbreaks and it did not differ for PFGE and MLVA. We applied the well established MLVA method to detect two S. Enteritidis foodborne outbreaks and find their sources successfully in 2014. A MLVA database of 491 S. Enteritidis strains isolated from 2004 to 2014 was established for the surveillance of clusters in the future. CONCLUSIONS: MLVA typing of S. Enteritidis would be an effective tool for early warning and epidemiological surveillance of S. Enteritidis infections. PMID- 26823187 TI - Soft Surfaces for the Reversible Control of Thin-Film Microstructure and Optical Reflectance. AB - A micromechano-optical material is rapidly and reversibly switched between distinct states of reflectance by simply stretching and relaxing the hybrid structure. The material is fabricated and controlled by leveraging the ability of soft elastic substrates to regulate the growth and morphological evolution of a chemically deposited polycrystalline thin film. PMID- 26823188 TI - A perovskite cell with a record-high-V(oc) of 1.61 V based on solvent annealed CH3NH3PbBr3/ICBA active layer. AB - A high open-circuit voltage inverted perovskite solar cell based on a CH3NH3PbBr3 absorber and ICBA acceptor is reported. The CH3NH3PbBr3 film fabricated under ambient atmosphere at a moderate temperature (~100 degrees C) using a two-step spin-coating method is composed of aggregated nano-grains. Upon solvent annealing of the CH3NH3PbBr3/ICBA film, the efficiency of the resulting cell increases from 1.71% to 7.50% with a remarkably high open circuit voltage (Voc) of ca. 1.60 V. ICBA acts not only as a high LUMO acceptor to realize high Voc but also as a mending agent to increase the efficiency of the cell by penetrating into the defects/voids of the CH3NH3PbBr3 film via solvent annealing as evidenced by TRPL, XPS and SEM data. Solvent annealing of the active layer was proved to be simple and effective device engineering to improve the efficiency of the perovskite cell based on a low quality film and the Voc of the inverted perovskite cell can be tuned by the LUMO level of the acceptor were revealed. The CH3NH3PbBr3/ICBA film is semi-transparent with an average 50% transmittance under visible light. The moderatetemperature processed CH3NH3PbBr3 solar cell with high Voc and a semi transparent absorber has great potential for application as the top cell in a tandem solar cell. PMID- 26823189 TI - Assessment of diet and recognition of nutritional deficiencies in paleopathological studies: A review. AB - An essential part of paleopathology is the study of diet and nutrition as well as inferring aspects of diet and nutrition from the skeletal pathology. Interpretation of nutritional and metabolic disease-related pathologies often provides additional insight into the daily social and cultural practices of people. However, precise diagnoses of specific vitamin-related deficiencies in archaeological skeletal remains are still quite problematic and specific diagnoses are rarely possible. This partly stems from the fact that many nutritional or metabolic diseases do not necessarily result in an osteological response and when they do, the comorbidity and analogous osteological responses to vitamin deficiencies may hamper the definite diagnosis of nutrition-related disease. Clin. Anat. 29:862-869, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26823190 TI - 3off2: A network reconstruction algorithm based on 2-point and 3-point information statistics. AB - BACKGROUND: The reconstruction of reliable graphical models from observational data is important in bioinformatics and other computational fields applying network reconstruction methods to large, yet finite datasets. The main network reconstruction approaches are either based on Bayesian scores, which enable the ranking of alternative Bayesian networks, or rely on the identification of structural independencies, which correspond to missing edges in the underlying network. Bayesian inference methods typically require heuristic search strategies, such as hill-climbing algorithms, to sample the super-exponential space of possible networks. By contrast, constraint-based methods, such as the PC and IC algorithms, are expected to run in polynomial time on sparse underlying graphs, provided that a correct list of conditional independencies is available. Yet, in practice, conditional independencies need to be ascertained from the available observational data, based on adjustable statistical significance levels, and are not robust to sampling noise from finite datasets. RESULTS: We propose a more robust approach to reconstruct graphical models from finite datasets. It combines constraint-based and Bayesian approaches to infer structural independencies based on the ranking of their most likely contributing nodes. In a nutshell, this local optimization scheme and corresponding 3off2 algorithm iteratively "take off" the most likely conditional 3-point information from the 2-point (mutual) information between each pair of nodes. Conditional independencies are thus derived by progressively collecting the most significant indirect contributions to all pairwise mutual information. The resulting network skeleton is then partially directed by orienting and propagating edge directions, based on the sign and magnitude of the conditional 3-point information of unshielded triples. The approach is shown to outperform both constraint-based and Bayesian inference methods on a range of benchmark networks. The 3off2 approach is then applied to the reconstruction of the hematopoiesis regulation network based on recent single cell expression data and is found to retrieve more experimentally ascertained regulations between transcription factors than with other available methods. CONCLUSIONS: The novel information-theoretic approach and corresponding 3off2 algorithm combine constraint-based and Bayesian inference methods to reliably reconstruct graphical models, despite inherent sampling noise in finite datasets. In particular, experimentally verified interactions as well as novel predicted regulations are established on the hematopoiesis regulatory networks based on single cell expression data. PMID- 26823191 TI - What Competencies Should Medical Students Attain in Nutritional Medicine? PMID- 26823192 TI - Stereological estimation of particle shape and orientation from volume tensors. AB - In the present paper, we describe new robust methods of estimating cell shape and orientation in 3D from sections. The descriptors of 3D cell shape and orientation are based on volume tensors which are used to construct an ellipsoid, the Miles ellipsoid, approximating the average cell shape and orientation in 3D. The estimators of volume tensors are based on observations in several optical planes through sampled cells. This type of geometric sampling design is known as the optical rotator. The statistical behaviour of the estimator of the Miles ellipsoid is studied under a flexible model for 3D cell shape and orientation. In a simulation study, the lengths of the axes of the Miles ellipsoid can be estimated with coefficients of variation of about 2% if 100 cells are sampled. Finally, we illustrate the use of the developed methods in an example, involving neurons in the medial prefrontal cortex of rat. PMID- 26823193 TI - Human predation contributed to the extinction of the Australian megafaunal bird Genyornis newtoni ~47 ka. AB - Although the temporal overlap between human dispersal across Australia and the disappearance of its largest animals is well established, the lack of unambiguous evidence for human-megafauna interactions has led some to question a human role in megafaunal extinction. Here we show that diagnostic burn patterns on eggshell fragments of the megafaunal bird Genyornis newtoni, found at >200 sites across Australia, were created by humans discarding eggshell in and around transient fires, presumably made to cook the eggs. Dating by three methods restricts their occurrence to between 53.9 and 43.4 ka, and likely before 47 ka. Dromaius (emu) eggshell occur frequently in deposits from >100 ka to present; burnt Dromaius eggshell first appear in deposits the same age as those with burnt Genyornis eggshell, and then continually to modern time. Harvesting of their eggs by humans would have decreased Genyornis reproductive success, contributing to the bird's extinction by ~47 ka. PMID- 26823195 TI - The relationship between line bisection performance and emotion processing: Where do you draw the line? AB - A recent study demonstrated that higher accuracy on a line bisection task related to greater ratings of evocative impact from paintings. The authors suggested that line bisection accuracy may act as a "barometer" for both visuospatial and emotion processing, likely as a function of overlapping neural correlates in the right temporoparietal region. We suggest and test an alternative explanation: that visuospatial bias interacted with asymmetries in the paintings and the rating scales to produce the apparent relationship between emotion and visuospatial functions. In the present study, using both visual-analogue and numeric rating scales, the relationship between line bisection performance and ratings of paintings (evocative impact, aesthetics, novelty, technique, and closure) was examined in a young adult sample. We demonstrate that left-hand line bisection bias direction, not line bisection accuracy, is related to most ratings, and that line bisection bias interacts with stimulus orientation (non mirrored/mirrored) and rating scale direction (ascending/descending) in such a way that can explain the results of the previous study. We conclude that the line bisection task appears to be a sensitive measure of visuospatial attentional biases, which can influence ratings of asymmetrical paintings, and may affect how individuals perceive stimuli in their environment. PMID- 26823194 TI - Functional hearing deficits in children with Type 1 diabetes. AB - AIM: Hearing loss (as reflected by abnormal sound detection) is a frequently reported consequence of Type 1 diabetes mellitus. We sought to evaluate sound detection, auditory neural function and binaural processing ability in a group of school-aged participants with Type 1 diabetes and to assess their functional hearing and general communication ability. METHODS: A range of electroacoustic, electrophysiological and behavioural test techniques were used to evaluate both cochlear and auditory neural function in 19 affected children. A cohort of matched controls was also assessed. RESULTS: Although all of the participants with Type 1 diabetes enjoyed normal sound detection, 9 of the 19 (47%) showed evidence of auditory pathway abnormality with evoked potential latencies and/or amplitudes beyond age-related norms. Auditory brainstem response interpeak latencies (wave I-V) were longer than in matched controls [ 95% confidence interval (95% CI); 0.10, 0.28 ms: P < 0.001] and wave V amplitudes were reduced (95% CI; -0.21, 0.00 MUV: P = 0.02). Binaural speech perception in noise was also impaired (95% CI; 0.82, 3.17 dB: P = 0.002) and perceptual ability was correlated with degree of neural disruption in the auditory brainstem (r = 0.662, P = 0.003). CONCLUSIONS: Hearing deficits severe enough to restrict communication and threaten academic progress were common on our group of school-aged children with Type 1 diabetes. Evaluation of both cochlear and auditory neural function may form an important part of the standard management regime for children with diabetes. PMID- 26823196 TI - Quantum Hash function and its application to privacy amplification in quantum key distribution, pseudo-random number generation and image encryption. AB - Quantum information and quantum computation have achieved a huge success during the last years. In this paper, we investigate the capability of quantum Hash function, which can be constructed by subtly modifying quantum walks, a famous quantum computation model. It is found that quantum Hash function can act as a hash function for the privacy amplification process of quantum key distribution systems with higher security. As a byproduct, quantum Hash function can also be used for pseudo-random number generation due to its inherent chaotic dynamics. Further we discuss the application of quantum Hash function to image encryption and propose a novel image encryption algorithm. Numerical simulations and performance comparisons show that quantum Hash function is eligible for privacy amplification in quantum key distribution, pseudo-random number generation and image encryption in terms of various hash tests and randomness tests. It extends the scope of application of quantum computation and quantum information. PMID- 26823197 TI - Correction: Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents. AB - Correction for 'Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents' by Roxanne Hachani et al., Nanoscale, 2015, DOI: 10.1039/c5nr03867g. PMID- 26823198 TI - The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). AB - Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. Despite its high prevalence, only a small minority of affected patients develops inflammation and subsequently fibrosis and chronic liver disease, while most of them only exhibit simple steatosis. In this context, the full understanding of the mechanisms underlying the development of NAFLD and non-alcoholic steatohepatitis (NASH) is of extreme importance; despite advances in this field, knowledge on the pathogenesis of NAFLD is still incomplete. The 'two-hit' hypothesis is now obsolete, as it is inadequate to explain the several molecular and metabolic changes that take place in NAFLD. The "multiple hit" hypothesis considers multiple insults acting together on genetically predisposed subjects to induce NAFLD and provides a more accurate explanation of NAFLD pathogenesis. Such hits include insulin resistance, hormones secreted from the adipose tissue, nutritional factors, gut microbiota and genetic and epigenetic factors. In this article, we review the factors that form this hypothesis. PMID- 26823199 TI - Genotype-phenotype relationships in familial amyotrophic lateral sclerosis with FUS/TLS mutations in Japan. AB - INTRODUCTION: We investigated possible genotype-phenotype correlations in Japanese patients with familial amyotrophic lateral sclerosis (FALS) carrying fused in sarcoma/translated in liposarcoma (FUS/TLS) gene mutations. METHODS: A consecutive series of 111 Japanese FALS pedigrees were screened for copper/zinc superoxide dismutase 1 (SOD1) and FUS/TLS gene mutations. Clinical data, including onset age, onset site, disease duration, and extramotor symptoms, were collected. RESULTS: Nine different FUS/TLS mutations were found in 12 pedigrees. Most of the patients with FUS/TLS-linked FALS demonstrated early onset in the brainstem/upper cervical region, and relatively short disease duration. A few mutations exhibited phenotypes that were distinct from typical cases. Frontotemporal dementia was present in 1 patient. CONCLUSIONS: This study revealed a characteristic phenotype in FUS/TLS-linked FALS patients in Japan. FUS/TLS screening is recommended in patients with FALS with this phenotype. Muscle Nerve 54: 398-404, 2016. PMID- 26823201 TI - Enzymatic Oxydate-Triggered Self-Illuminated Photoelectrochemical Sensing Platform for Portable Immunoassay Using Digital Multimeter. AB - Herein a novel split-type photoelectrochemical (PEC) immunosensing platform was designed for sensitive detection of low-abundance biomarkers (prostate-specific antigen, PSA, used in this case) by coupling a peroxyoxalate chemiluminescence (PO-CL) self-illuminated system with digital multimeter (DMM) readout. The PEC detection device consisted of a capacitor/DMM-joined electronic circuit and a PO CL-based self-illuminated cell. Initially, reduced graphene oxide-doped BiVO4 (BiVO4-rGO) photovoltaic materials with good photoelectric properties was integrated into the capacitor/DMM-joined circuit for photocurrent generation in the presence of hydrogen peroxide (H2O2, as the hole-trapping reagent). A sandwich-type immunoreaction with target PSA was carried out in capture antibody coated microplates by using glucose oxidase/detection antibody-conjugating gold nanoparticle (pAb2-AuNP-GOx). Accompanying the sandwiched immunocomplex, the labeled GOx could oxidize glucose to produce H2O2. The as-generated H2O2 could act as the coreaction reagent to trigger the chemiluminescence of the peroxyoxalate system and the PEC reaction of the BiVO4-rGO. Meanwhile, the self illuminated light could induce photovoltaic material (BiVO4-rGO) to produce a voltage that was utilized to charge an external capacitor. With the switch closed, the capacitor could discharge through the DMM and provide an instantaneous current. Different from conventional PEC immunoassays, the as generated photoelectron was stored in the capacitor and released instantaneously to amplify the photocurrent. Under the optimal conditions, the transient current increased with the increasing target PSA concentration in the dynamic working range from 10 pg mL(-1) to 80 ng mL(-1) with a detection limit (LOD) of 3 pg mL( 1). This work demonstrated for the first time that the peroxyoxalate CL system could be used as a suitable substitute of physical light source to apply in PEC immunoassay. In addition, this methodology afforded good reproducibility, precision, and high specificity, and the method accuracy matched well with the commercial PSA ELISA kit. Importantly, the developed split-type photoelectrochemical immunoassay could not only avoid the interfering of the biomolecules relative to the photovoltaic materials but also eliminate the need of an exciting light source and expensive instrumentation, thus representing a user-friendly and low-cost assay protocol for practical utilization in quantitative low-abundance proteins. PMID- 26823200 TI - Transient Ciliochoroidal Detachment After Ab Interno Trabeculotomy for Open-Angle Glaucoma: A Prospective Anterior-Segment Optical Coherence Tomography Study. AB - IMPORTANCE: Although trabeculotomy is a glaucoma surgical procedure for modest intraocular pressure (IOP) reduction, some eyes exhibit very low IOP during the early postoperative period. To our knowledge, the reason and its effect have not been investigated. OBJECTIVES: To investigate ciliochoroidal detachment (CCD) immediately after ab interno trabeculotomy and evaluate its effect on IOP immediately after surgery. DESIGN, SETTING, AND PARTICIPANTS: This prospective, observational, case series was conducted at Kyoto University Hospital, Kyoto, Japan. Patients with open-angle glaucoma who underwent ab interno trabeculotomy using a microsurgical device by a single surgeon between July 1, 2014, and May 31, 2015, were included. Thirty-seven consecutive patients were enrolled, 33 of whom were included in the analysis. The dates of the analysis were August 1 to August 15, 2015. INTERVENTION: Imaging of CCD using anterior-segment optical coherence tomography (AS-OCT). MAIN OUTCOMES AND MEASURES: The incidence of CCD immediately after ab interno trabeculotomy and its effect on IOP in the early postoperative period. RESULTS: The study cohort comprised 33 patients. Their mean (SD) age was 69.4 (13.2) years, and 19 (58%) were male. At postoperative day 3, CCD was detected in 14 of 33 eyes (42%) (CCD group) using AS-OCT. The CCD group had shorter axial length (mean [SD], 23.66 [1.67] vs 25.16 [1.59] mm) and thinner central corneal thickness (mean [SD], 505.9 [35.8] vs 533.9 [39.1] MUm) than the non-CCD group. Only 5 eyes had CCD at postoperative day 10, and 4 of these eyes had CCD at 1 month after surgery. The postoperative IOPs at all follow-up periods were lower in the CCD group than in the non-CCD group, but the difference in the postoperative IOPs between the groups decreased as time passed. The mean (SD) IOPs for the CCD group vs the non-CCD group were 9.1 (3.0) vs 14.2 (5.8) mm Hg at day 1, 8.4 (2.4) vs 13.4 (5.0) mm Hg at day 3, 11.0 (3.0) vs 15.5 (6.3) mm Hg at day 10, 13.4 (2.4) vs 15.5 (3.3) mm Hg at 1 month, and 13.9 (3.4) vs 15.5 (4.0) mm Hg at 3 months. In several eyes in the CCD group, the AS-OCT images revealed a connection between the CCD and the anterior chamber via the trabeculotomy site. CONCLUSIONS AND RELEVANCE: Ciliochoroidal detachment after ab interno trabeculotomy was not rare and was associated with low IOP immediately after surgery. Postoperative CCD may be partially attributed to the transient increase in uveoscleral aqueous outflow via the trabeculotomy site. PMID- 26823202 TI - Why dedicate yourself to bioethics? Seven reasons to get you started. AB - The aim of clinical bioethics is to promote rational clinical decisions that take into account the clinical facts and the preferences and values of individuals involved in a situation that entails a moral problem. The objective of the present study is to list the reasons why we consider bioethics knowledge and skills to be essential in daily practice and to promote a proactive mindset in clinical bioethics research. The arguments set forth include the need to adapt to changes in the clinical relationship in recent decades, the importance of an ethical approach both for the physician and the patient, the role of bioethics in preventing professional burnout, the ability of ethics to promote a more equitable distribution of resources and the possibility of conducting clinical research in bioethics, a field that has scarcely been explored in Spain. PMID- 26823203 TI - Indocyanine green angiographic findings in initial-onset acute Vogt-Koyanagi Harada disease. AB - PURPOSE: To study the features of Indocyanine green angiography (ICGA) in patients with initial-onset acute Vogt-Koyanagi-Harada (VKH) disease. METHODS: Retrospective cohort study of ICGA performed with the use of Heidelberg scanning laser ophthalmoscope on a consecutive series of patients with initial-onset acute VKH disease. The following signs were analysed: choroidal perfusion inhomogeneity, early hyperfluorescent stromal vessels, hypofluorescent dark dots (HDDs), fuzzy or lost pattern of large stromal choroidal vessels, disc hyperfluorescence, and, diffuse late choroidal hyperfluorescence. In addition, we looked for any new ICGA findings. RESULTS: Thirty-six patients (72 eyes) from a single academic institution were studied. The following findings were identified: HDDs in all eyes (100%), fuzzy or lost pattern of large stromal vessels in all eyes (100%), early hyperfluorescent stromal vessels were seen in 60 eyes (83%), diffuse late choroidal hyperfluorescence was present in 51 eyes (71%), choroidal perfusion inhomogeneity was seen in 44 eyes (61%), disc hyperfluorescence was seen in 25 cases (69%), and choroidal folds were present in only six eyes. New ICGA findings detected in this study were hypofluorescent patches corresponding to areas of exudative retinal detachment in 60 eyes (83%) and 'starry sky' pattern of late widespread punctate choroidal hyperfluorescence in 37 eyes (51%). CONCLUSIONS: The most prevalent ICGA findings were HDDs, fuzzy stromal vessels and early hyperfluorescent stromal vessels in patients with initial-onset acute VKH disease. Novel ICGA findings in this group of patients included hypofluorescent patches corresponding to areas of exudative retinal detachment, and late widespread punctate choroidal hyperfluorescence taking on a 'starry sky' pattern. PMID- 26823204 TI - The differential effects of presenting uncertainty around benefits and harms on treatment decision making. AB - OBJECTIVE: The study aimed to determine the effects of presenting uncertainty of quantitative risk information about medication harms and benefits on intention to take medication and psychosocial outcomes. METHODS: 147 participants were randomized into four hypothetical scenarios: (1) harm/benefit presented as point estimates, (2) harm as point/benefit as range, (3) harm as range/benefit as point, (4) harm/benefit as ranges. We assessed participants' intention to take medication, understanding, decisional conflict, and perceived benefit and harm. Participants viewed the scenario again with swapped range vs. point-estimate presentations; intention was re-assessed at time 2. RESULTS: There were no significant differences in intention across arms (p=0.93). There was an increase in intention to take medication between time 1 and time 2 in arm 4 (both harm/benefit presented as ranges, then point estimates). Understanding was greater when information was presented as point estimates compared to ranges, for both benefit (all questions correct: 74% vs 42%; chi2=15.28, df=2, p<0.001) and harm (all questions correct: 70% vs 43%; chi2=11.19, df=2, p=0.004) CONCLUSION: Changes in benefit information appear to be more influential in changing intention to take medication than harm information. Presenting uncertainty decreases understanding of information. PRACTICE IMPLICATION: The findings may help develop optimal ways to present uncertainty. PMID- 26823205 TI - Facial Skin Lesions in Children Caused by Nontuberculous Mycobacteria. AB - BACKGROUND: Nontuberculous mycobacteria rarely cause facial skin lesions in immunocompetent children. AIM: I describe the clinical features and treatment of nontuberculous mycobacteria facial lesions. MATERIALS AND METHODS: The diagnosis of a facial nontuberculous mycobacteria infection was established using polymerase chain reaction. RESULTS: Of 286 children with confirmed nontuberculous mycobacteria infection, 14 (4.9%; median age 50 mos, range 9-156 mos; 5 [36%] male, 9 [64%] female) had nontuberculous mycobacteria facial skin lesions. Six (43%) had lesions on the cheek and five (36%) in the medial eye corner. Polymerase chain reaction results confirmed the presence of Mycobacterium haemophilum in eight patients (57%) and Mycobacterium avium in six patients (43%). The facial lesions were treated using a combination of clarithromycin and rifabutin for 12 weeks, with a median healing time of 4 months. CONCLUSION: Nontuberculous mycobacteria facial lesions are rare in immunocompetent children. The diagnosis requires a high index of suspicion. Nonsurgical treatment is preferable, because surgical excision of the cutaneous lesions might lead to undesirable visible facial scars. PMID- 26823206 TI - The RNA-binding protein Mex3B is a coreceptor of Toll-like receptor 3 in innate antiviral response. AB - Recognition of viral dsRNA by Toll-like receptor 3 (TLR3) leads to induction of interferons (IFNs) and proinflammatory cytokines, and innate antiviral response. Here we identified the RNA-binding protein Mex3B as a positive regulator of TLR3 mediated signaling by expression cloning screens. Cells from Mex3b(-/-) mice exhibited reduced production of IFN-beta in response to the dsRNA analog poly(I:C) but not infection with RNA viruses. Mex3b(-/-) mice injected with poly(I:C) was more resistant to poly(I:C)-induced death. Mex3B was associated with TLR3 in the endosomes. It bound to dsRNA and increased the dsRNA-binding activity of TLR3. Mex3B also promoted the proteolytic processing of TLR3, which is critical for its activation. Mutants of Mex3B lacking its RNA-binding activity inhibited TLR3-mediated IFN-beta induction. These findings suggest that Mex3B acts as a coreceptor of TLR3 in innate antiviral response. PMID- 26823207 TI - Arresting supporters: targeting neutrophils in metastasis. AB - It is becoming increasingly clear that leukocytes dynamically regulate cancer progression and metastasis, and among leukocytes, granulocytic cells abundantly accumulate in metastatic organs; however, their function in metastasis remains controversial. In a recent report in Nature, Wculek and Malanchi clarify the role of mature neutrophils as mediators of metastatic initiation and provide a targeted approach to prevent the pro-metastatic activity of neutrophils in breast cancer models. PMID- 26823208 TI - Do knowledge of uterine artery resistance in the second trimester and targeted surveillance improve maternal and perinatal outcome? UTOPIA study: a randomized controlled trial. AB - OBJECTIVES: To ascertain whether screening for pre-eclampsia (PE) and intrauterine growth restriction (IUGR) by uterine artery (UtA) Doppler in the second trimester of pregnancy and targeted surveillance improve maternal and perinatal outcomes in an unselected population. METHODS: This was a multicenter randomized open-label controlled trial. At the routine second-trimester anomaly scan, women were assigned randomly to UtA Doppler or non-Doppler groups. Women with abnormal UtA Doppler were offered intensive surveillance at high-risk clinics of the participating centers with visits every 4 weeks that included measurement of maternal blood pressure, dipstick proteinuria, fetal growth and Doppler examination. The primary outcome was a composite score for perinatal complications, defined as the presence of any of the following: PE, IUGR, spontaneous labor < 37 weeks' gestation, placental abruption, stillbirth, gestational hypertension, admission to neonatal intensive care unit and neonatal complications. Secondary outcomes were a composite score for maternal complications (disseminated intravascular coagulation, maternal mortality, postpartum hemorrhage, pulmonary edema, pulmonary embolism, sepsis), and medical interventions (for example, corticosteroid administration and induction of labor) in patients developing placenta-related complications. RESULTS: In total, 11 667 women were included in the study. Overall, PE occurred in 348 (3.0%) cases, early onset PE in 48 (0.4%), IUGR in 722 (6.2%), early-onset IUGR in 93 (0.8%) and early-onset PE with IUGR in 32 (0.3%). UtA mean pulsatility index > 90(th) percentile was able to detect 59% of early-onset PE and 60% of early-onset IUGR with a false-positive rate of 11.1%. When perinatal and maternal data according to assigned group (UtA Doppler vs non-Doppler) were compared, no differences were found in perinatal or maternal complications. However, screened patients had more medical interventions, such as corticosteroid administration (relative risk (RR), 1.79 (95% CI, 1.4-2.3)) and induction of labor for IUGR (RR, 1.36 (95% CI, 1.07 1.72)). In women developing PE or IUGR, there was a trend towards fewer maternal complications (RR, 0.46 (95% CI, 0.19-1.11)). CONCLUSIONS: Routine second trimester UtA Doppler ultrasound in an unselected population identifies approximately 60% of women at risk for placental complications; however, application of this screening test failed to improve short-term maternal and neonatal morbidity and mortality. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26823209 TI - Experimental arthritis: A chilling link to joint pain and hypersensitivity. PMID- 26823210 TI - The efficacy of fluticasone furoate administered in the morning or evening is comparable in patients with persistent asthma. AB - BACKGROUND: The inhaled corticosteroid fluticasone furoate (FF) is efficacious as a once-daily treatment for the management of asthma. Asthma is associated with circadian changes, with worsening lung function at night. We compared the efficacy of once-daily FF in the morning or evening for the treatment of asthma. METHODS: Adults with persistent bronchial asthma were enrolled into this randomised, repeat-dose, double-blind, double-dummy, placebo-controlled, three way crossover study. After a 14-day run-in period, patients received either: FF 100 MUg in the morning (AM); FF 100 MUg in the evening (PM); or placebo, via the ELLIPTA((r)) dry powder inhaler. Patients received all three treatments (14 +/- 2 day duration) separated by a 14- to 21-day washout period. The primary endpoint was 24-h weighted mean forced expiratory volume in 1 s (FEV1) measured at the end of each 14-day treatment. RESULTS: A total of 28 patients aged between 19 and 67 years were randomised and 21 (75%) completed all three study arms. Once-daily administration of FF 100 MUg resulted in an increased 24-hour weighted mean FEV1; differences between the adjusted means for AM and PM FF dosing versus placebo were 0.077 L (90% confidence interval [CI]: 0.001, 0.152) and 0.105 L (90% CI: 0.029, 0.180), respectively (adjusted mean difference: -0.028 L [90% CI: -0.102, 0.045]). AM or PM doses had comparable incidences of adverse events (AEs; 18/23 versus 18/24, respectively), no serious AEs occurred. CONCLUSION: AM and PM doses of once-daily FF 100 MUg produced comparable improvements in lung function relative to placebo. PMID- 26823211 TI - Bronchodilator response as a marker of poor asthma control. AB - BACKGROUND: Asthma guidelines emphasise the importance of monitoring disease control in managing asthma. OBJECTIVE: The aim of this study was to evaluate the relationship between lung function, including bronchodilator response in terms of improving in FEV1 after administration of salbutamol, and asthma control. METHODS: 246 patients with known asthma and in regular chronic treatment according to international guidelines were consecutively enrolled in a 12 month period. All patients were evaluated by asthma control test (ACT), spirometry and bronchodilator test with salbutamol 400 mcg. RESULTS: Mean ACT value was 18.8. Patients with significant bronchial reversibility had lower ACT mean values. This finding was confirmed in both patients with airway obstruction and in those with normal spirometry. There was a significant correlation between ACT values and bronchodilator response. CONCLUSIONS: The persistence of a significant degree of bronchodilator response despite regular treatment according to guidelines was a marker of worse asthma control. CLINICAL IMPLICATIONS: Bronchodilator response, correlating with worse asthma control even in patients with normal spirometry, should be test at every visit as it may add information on asthma control. PMID- 26823212 TI - What are the characteristics of asthma patients with elevated serum IgG4 levels? AB - INTRODUCTION: IgG4 has recently been a subject of great interest in human pathology. No data are available about the characteristics of asthma patients with elevated IgG4 levels. POPULATION AND METHODS: An observational study was conducted from January 2006 to March 2015 in a difficult-to-treat population of asthma patients. Twenty-six difficult-to-treat asthma patients with elevated serum IgG4 levels (IgG4/IgG ratio up to 10%) were compared with a control population of 98 difficult-to-treat asthma patients with normal serum IgG4. Blood eosinophilia, total IgE and FeNO were compared between groups to better characterize asthma patients with elevated serum IgG4 levels. RESULTS: Median IgG4 concentrations were 1.72 g/l [1.19-2.36] and 0.22 g/l [0.10-0.49] in the elevated IgG4 group and normal Ig4 group, respectively. Median blood eosinophilia was more than three times higher in patients with elevated serum IgG4 levels than in controls (0.75 10(9)/L [IQR 0.54-1.78] vs 0.22 10(9)/L [IQR 0.09-0.54] respectively, p < 0.0001). Total IgE was twice as high (264.5 kUI/l [IQR 166.3 779] vs 126 kUI/l [IQR 26-350] respectively; p < 0.05) and FeNO was nearly twice as high (61 [IQR 41-111] ppb vs 35 [IQR 23-51] ppb, p < 0.001). Allergic broncho pulmonary aspergillosis (ABPA) and eosinophilic granulomatosis with polyangiitis (EGPA) were observed in the asthma patients with elevated serum IgG4. Ten patients had unexplained increased blood eosinophilia. CONCLUSION: Asthma patients with elevated IgG4 levels have significantly higher blood eosinophilia, total IgE and FeNO. ABPA and EGPA are observed in patients with elevated serum IgG4. PMID- 26823214 TI - Effect of pentavalent rotavirus vaccine introduction on hospital admissions for diarrhoea and rotavirus in children in Rwanda: a time-series analysis. AB - BACKGROUND: In May, 2012, Rwanda became the first low-income African country to introduce pentavalent rotavirus vaccine into its routine national immunisation programme. Although the potential health benefits of rotavirus vaccination are huge in low-income African countries that account for more than half the global deaths from rotavirus, concerns remain about the performance of oral rotavirus vaccines in these challenging settings. METHODS: We conducted a time-series analysis to examine trends in admissions to hospital for non-bloody diarrhoea in children younger than 5 years in Rwanda between Jan 1, 2009, and Dec 31, 2014, using monthly discharge data from the Health Management Information System. Additionally, we reviewed the registries in the paediatric wards at six hospitals from 2009 to 2014 and abstracted the number of total admissions and admissions for diarrhoea in children younger than 5 years by admission month and age group. We studied trends in admissions specific to rotavirus at one hospital that had undertaken active rotavirus surveillance from 2011 to 2014. We assessed changes in rotavirus epidemiology by use of data from eight active surveillance hospitals. FINDINGS: Compared with the 2009-11 prevaccine baseline, hospital admissions for non-bloody diarrhoea captured by the Health Management Information System fell by 17-29% from a pre-vaccine median of 4051 to 2881 in 2013 and 3371 in 2014, admissions for acute gastroenteritis captured in paediatric ward registries decreased by 48-49%, and admissions specific to rotavirus captured by active surveillance fell by 61-70%. The greatest effect was recorded in children age-eligible to be vaccinated, but we noted a decrease in the proportion of children with diarrhoea testing positive for rotavirus in almost every age group. INTERPRETATION: The number of admissions to hospital for diarrhoea and rotavirus in Rwanda fell substantially after rotavirus vaccine implementation, including among older children age-ineligible for vaccination, suggesting indirect protection through reduced transmission of rotavirus. These data highlight the benefits of routine vaccination against rotavirus in low-income settings. FUNDING: Gavi, the Vaccine Alliance and the Government of Rwanda. PMID- 26823215 TI - Stillbirths: still neglected? PMID- 26823213 TI - Effect of participatory women's groups facilitated by Accredited Social Health Activists on birth outcomes in rural eastern India: a cluster-randomised controlled trial. AB - BACKGROUND: A quarter of the world's neonatal deaths and 15% of maternal deaths happen in India. Few community-based strategies to improve maternal and newborn health have been tested through the country's government-approved Accredited Social Health Activists (ASHAs). We aimed to test the effect of participatory women's groups facilitated by ASHAs on birth outcomes, including neonatal mortality. METHODS: In this cluster-randomised controlled trial of a community intervention to improve maternal and newborn health, we randomly assigned (1:1) geographical clusters in rural Jharkhand and Odisha, eastern India to intervention (participatory women's groups) or control (no women's groups). Study participants were women of reproductive age (15-49 years) who gave birth between Sept 1, 2009, and Dec 31, 2012. In the intervention group, ASHAs supported women's groups through a participatory learning and action meeting cycle. Groups discussed and prioritised maternal and newborn health problems, identified strategies to address them, implemented the strategies, and assessed their progress. We identified births, stillbirths, and neonatal deaths, and interviewed mothers 6 weeks after delivery. The primary outcome was neonatal mortality over a 2 year follow up. Analyses were by intention to treat. This trial is registered with ISRCTN, number ISRCTN31567106. FINDINGS: Between September, 2009, and December, 2012, we randomly assigned 30 clusters (estimated population 156 519) to intervention (15 clusters, estimated population n=82 702) or control (15 clusters, n=73 817). During the follow-up period (Jan 1, 2011, to Dec 31, 2012), we identified 3700 births in the intervention group and 3519 in the control group. One intervention cluster was lost to follow up. The neonatal mortality rate during this period was 30 per 1000 livebirths in the intervention group and 44 per 1000 livebirths in the control group (odds ratio [OR] 0.69, 95% CI 0.53 0.89). INTERPRETATION: ASHAs can successfully reduce neonatal mortality through participatory meetings with women's groups. This is a scalable community-based approach to improving neonatal survival in rural, underserved areas of India. FUNDING: Big Lottery Fund (UK). PMID- 26823216 TI - Participatory women's groups: time for integration into programmes. PMID- 26823217 TI - Success of rotavirus vaccination in Africa: good news and remaining questions. PMID- 26823218 TI - Double burden of tragedy: stillbirth and obstetric fistula. PMID- 26823219 TI - New roles for global health: diplomatic, security, and foreign policy responsiveness. PMID- 26823220 TI - Borders and migration: an issue of global health importance. PMID- 26823221 TI - The need to contextualise psychotraumatology research. PMID- 26823222 TI - To be or not to be exclusive: the sutezolid story. PMID- 26823223 TI - To be or not to be exclusive: the sutezolid story. PMID- 26823224 TI - The Raffles Dialogue on Human Wellbeing and Security. PMID- 26823225 TI - The Raffles Dialogue on Human Wellbeing and Security - Authors' reply. PMID- 26823226 TI - Xpert MTB/RIF for tuberculosis testing: access and price in highly privatised health markets. PMID- 26823228 TI - Osseoperception in Dental Implants: A Systematic Review. AB - PURPOSE: Replacement of lost teeth has significant functional and psychosocial effects. The capability of osseointegrated dental implants to transmit a certain amount of sensibility is still unclear. The phenomenon of developing a certain amount of tactile sensibility through osseointegrated dental implants is called osseoperception. The aim of this article is to evaluate the available literature to find osseoperception associated with dental implants. MATERIALS AND METHODS: To identify suitable literature, an electronic search was performed using Medline and PubMed database. Articles published in English and articles whose abstract is available in English were included. The articles included in the review were based on osseoperception, tactile sensation, and neurophysiological mechanoreceptors in relation to dental implants. Articles on peri-implantitis and infection-related sensitivity were not included. Review articles without the original data were excluded, although references to potentially pertinent articles were noted for further follow-up. The phenomenon of osseoperception remains a matter of debate, so the search strategy mainly focused on articles on osseoperception and tactile sensibility of dental implants. This review presents the histological, neurophysiological, and psychophysical evidence of osseoperception and also the role of mechanoreceptors in osseoperception. RESULTS: The literature on osseoperception in dental implants is very scarce. The initial literature search resulted in 90 articles, of which 81 articles that fulfilled the inclusion criteria were included in this systematic review. CONCLUSION: Patients restored with implant-supported prostheses reported improved tactile and motor function when compared with patients wearing complete dentures. PMID- 26823227 TI - Transforming research results into useful tools for global health: BOOST. PMID- 26823229 TI - A Cobalt(I) Pincer Complex with an eta(2) -C(aryl)-H Agostic Bond: Facile C-H Bond Cleavage through Deprotonation, Radical Abstraction, and Oxidative Addition. AB - The synthesis and reactivity of a Co(I) pincer complex [Co(kappa(3) P,CH,P P(CH)P(NMe) -iPr)(CO)2](+) featuring an eta(2)-C(aryl)-H agostic bond is described. This complex was obtained by protonation of the Co(I) complex [Co(PCP(NMe) -iPr)(CO)2]. The Co(III) hydride complex [Co(PCP(NMe) iPr)(CNtBu)2(H)](+) was obtained upon protonation of [Co(PCP(NMe) -iPr)(CNtBu)2]. Three ways to cleave the agostic C-H bond are presented. First, owing to the acidity of the agostic proton, treatment with pyridine results in facile deprotonation (C-H bond cleavage) and reformation of [Co(PCP(NMe) -iPr)(CO)2]. Second, C-H bond cleavage is achieved upon exposure of [Co(kappa(3)P,CH,P P(CH)P(NMe) -iPr)(CO)2](+) to oxygen or TEMPO to yield the paramagnetic Co(II) PCP complex [Co(PCP(NMe) -iPr)(CO)2](+). Finally, replacement of one CO ligand in [Co(kappa(3) P,CH,P-P(CH)P(NMe) -iPr)(CO)2](+) by CNtBu promotes the rapid oxidative addition of the agostic eta(2) -C(aryl)-H bond to give two isomeric hydride complexes of the type [Co(PCP(NMe) -iPr)(CNtBu)(CO)(H)](+). PMID- 26823230 TI - Increased detection of coronary atherosclerosis on 320-slice computed tomographic angiography with burden of cardiovascular risk factors and complications in patients with type 2 diabetes. AB - AIMS: The cardiovascular risk factors and diabetic complications are related to coronary atherosclerosis. However, the evaluation of the prevalence of coronary atherosclerosis based on their accumulation remains to be determined. METHODS: 247 consecutive Chinese subjects with type 2 diabetes but without history of coronary heart disease (CHD) underwent 320-slice computed tomographic coronary angiography, including no coronary atherosclerosis, non-obstructive atherosclerosis (<50% stenosis) and obstructive atherosclerosis (>=50% stenosis). Conventional cardiovascular risk factors, albuminuria, renal dysfunction and diabetic retinopathy (DR) were determined. Framingham Risk Score (FRS) was used to assess the 10-year CHD risk. RESULTS: Increase in burden of cardiovascular risk factors and diabetic complications were significantly associated with the likelihood of being a higher coronary atherosclerosis category. In the analysis for trend through the categories of burden score or FRS stratification, the percentage of obstructive atherosclerosis was increased and the percentage of no atherosclerosis decreased as the burden score and FRS increased (all p<0.005), respectively. The areas under the receiver operator curve for the burden score versus FRS were greater at predicting coronary atherosclerosis and obstructive atherosclerosis (p=0.004 and p=0.002), respectively. CONCLUSIONS: The prevalence of coronary atherosclerosis was increased with the accumulation of cardiovascular risk factors and diabetic complications. The burden of these clinical and biochemical risk factors has increased ability for prediction of the presence and severity of coronary atherosclerosis over FRS in type 2 diabetic patients. PMID- 26823231 TI - The changing face of liver transplantation for acute liver failure: Assessment of current status and implications for future practice. AB - The etiology and outcomes of acute liver failure (ALF) have changed since the definition of this disease entity in the 1970s. In particular, the role of emergency liver transplantation has evolved over time, with the development of prognostic scoring systems to facilitate listing of appropriate patients, and a better understanding of transplant benefit in patients with ALF. This review examines the changing etiology of ALF, transplant benefit, outcomes following transplantation, and future alternatives to emergency liver transplantation in this devastating condition. PMID- 26823232 TI - The impact of the 2005 International Society of Urological Pathology consensus guidelines on Gleason grading - a matched-pair analysis. AB - OBJECTIVES: To investigate whether the International Society of Urological Pathology (ISUP) 2005 revision of the Gleason grading system has influenced the risk of biochemical recurrence (BCR) after radical prostatectomy (RP), as the new guideline implies that some prostate cancers previously graded as Gleason score 6 (3 + 3) are now considered as 7 (3 + 4). PATIENTS AND METHODS: A matched-pair analysis was conducted. In all, 215 patients with Gleason score 6 or 7 (3 + 4) prostate cancer on biopsy who underwent RP before 31 December 2005 (pre-ISUP group), were matched 1:1 by biopsy Gleason score, clinical tumour category, PSA level, and margin status to patients undergoing RP between 1 January 2008 and 31 December 2011 (post-ISUP group). Patients were followed until BCR defined as a PSA level of >=0.2 ng/mL. Risk of BCR was analysed in a competing-risk model. RESULTS: The median follow-up was 9.5 years in the pre-ISUP group and 4.8 years in the post-ISUP group. The 5-year cumulative incidences of BCR were 34.0% and 13.9% in the pre-ISUP and post-ISUP groups, respectively (P < 0.001). The difference in cumulative incidence applied to both patients with Gleason score 6 (P < 0.001) and 7 (3 + 4) (P = 0.004). There was no difference in the 5-year cumulative incidence of BCR between patients with pre-ISUP Gleason score 6 and post-ISUP Gleason score 7 (3 + 4) (P = 0.34). In a multiple Cox-proportional hazard regression model, ISUP 2005 grading was a strong prognostic factor for BCR within 5 years of RP (hazard ratio 0.34; 95% confidence interval 0.22-0.54; P < 0.001). CONCLUSION: The revision of the Gleason grading system has reduced the risk of BCR after RP in patients with biopsy Gleason score 6 and 7 (3 + 4). This may have consequences when comparing outcomes across studies and historical periods and may affect future treatment recommendations. PMID- 26823233 TI - Multicomponent Diene-Transmissive Diels-Alder Sequences Featuring Aminodendralenes. AB - 1-Aminodecalins were prepared from acyclic precursors by combining the powerful twofold diene-transmissive Diels-Alder chemistry of [3]dendralenes with the simplicity of enamine formation. On mixing at ambient temperature, a simple dienal condenses with a primary or secondary amine to generate the enamine, a 1 amino-[3]dendralene in situ, and this participates as a double diene in a sequence of two Diels-Alder events with separate dienophiles. Overall, four C-C bonds and one C-N bond are formed. Mechanistic insights into these reactions are provided by means of density functional theory calculations. PMID- 26823234 TI - Challenges Associated with Sample Preparation for the Analysis of PBDEs in Human Serum. AB - Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in many applications; however, certain PBDE congeners are persistent, bioaccumulative, and toxic to both humans and the environment. PBDEs have been found in human specimens, and a variety of analytical techniques have been used for their determination in biological matrixes. Nevertheless, obtaining a relatively clean analytical blank sample during PBDE analysis is a big challenge because of the ubiquitous nature of these compounds. Thus, the present study was conducted to compare the PBDE background levels associated with the three most commonly used extraction techniques: liquid-liquid extraction (LLE), SPE, and accelerated solvent extraction (ASE). Conventionally used blank matrixes (HPLC grade water, Milli-Q water, and air) were spiked with internal standards and extracted using LLE, SPE, or ASE. The extracts were analyzed by GC/electron ionization-tandem MS. The ASE method achieved the lowest background levels for nearly all the PBDE congeners analyzed, which may be attributed to the stainless steel and closed vessel nature of the ASE cells. PMID- 26823235 TI - Effect of self-performed mechanical plaque control frequency on gingival inflammation revisited: a randomized clinical trial. AB - AIM: To evaluate the effect of self-performed mechanical plaque control (SPC) frequency on gingival health. METHODS: Thirty-nine subjects exhibiting limited gingival inflammation and minimal clinical attachment loss were enrolled in a single-blind, parallel group, randomized clinical trial. The subjects that were divided into three groups were tasked to perform SPC (using tooth brush and dental floss) at 12, 24 or 48 h intervals. Gingival index (GI), plaque index (PlI), and gingival crevicular fluid (GCF) volume were evaluated at baseline and 30 days follow-up. Groups were compared using anova and Tukey. RESULTS: No significant differences in mean GI change were observed between the 12 and 24 h SPC intervals from baseline to 30 days (-0.06 +/- 0.13 versus 0.05 +/- 0.09; p = 0.11). In contrast, the 48 h interval had significantly higher mean GI change than the 12 and 24 h intervals (0.33 +/- 0.17; p = 0.001). Similarly, mean PlI change was not significantly different between the 12 and 24 h SPC intervals (0.11 versus 0.28; p = 0.15), whereas SPC at 48 h-intervals yielded a significantly increased PlI (0.39; p = 0.001). CONCLUSIONS: Self-performed mechanical plaque control performed at 12 h or 24 h intervals appears sufficient to maintain gingival health in subjects with no or limited clinical attachment loss. PMID- 26823236 TI - X-Linked Retinoschisis: Phenotypic Variability in a Chinese Family. AB - X-linked juvenile retinoschisis (XLRS), a leading cause of juvenile macular degeneration, is characterized by a spoke-wheel pattern in the macular region of the retina and splitting of the neurosensory retina. Our study is to describe the clinical characteristics of a four generations of this family (a total of 18 members)with X-linked retinoschisis (XLRS) and detected a novel mutations of c.3G > A (p.M1?) in the initiation codon of the RS1 gene. by direct sequencing.Identification of this mutation in this family provides evidence about potential genetic or environmental factors on its phenotypic variance, as patients presented with different phenotypes regardless of having the same mutation. Importantly, OCT has proven vital for XLRS diagnosis in children. PMID- 26823237 TI - Influence of white matter MRI hyper-intensities on acute l-dopa response in patients with Parkinson's disease. AB - OBJECTIVE: To determine whether brain white matter hyperintensities (WMH) influence l-dopa response in Parkinson's disease (PD) patients. METHODS: We prospectively evaluated 60 PD patients with an acute l-dopa challenge test, and assessed motor performance with the Movement Disorders Society revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS) during "ON" and "OFF" medication states. Magnetic resonance images were examined using a visual semi-quantitative rating scale for quantification and distribution analysis of WMH. l-dopa challenge test response was correlated to extent and location of WMH, to determine a potential association between them. RESULTS: Subjects with greater deep WMH burden, showed less response to l-dopa on axial motor symptoms (R = 0.35; p < 0.027), when tested with Part III of the MDS-UPDRS before and after acute levodopa challenge. CONCLUSIONS: Results suggest WMH may affect response to l-dopa on axial function of PD patients, which could be due to either non dopaminergic (cortico-basal ganglia) motor pathway disruption, or postsynaptic nigrostriatal pathway involvement. PMID- 26823238 TI - New onset progressive chorea with elevated striational antibody titers. PMID- 26823239 TI - Iodine Migration and its Effect on Hysteresis in Perovskite Solar Cells. AB - The migration and accumulation of iodide ions create a modulation of the respective interfacial barriers causing the hysteresis in solar cells based on methylammonium lead iodide perovskites. Iodide ions are identified as the migrating species by measuring temperature dependent current-transients and photoelectron spectroscopy. The involved changes in the built-in potential due to ion migration are directly measured by electroabsorption spectroscopy. PMID- 26823240 TI - Analgesic effects of acetaminophen, diclofenac and hyoscine N-butylbromide in second trimester pregnancy termination: a prospective randomized study. AB - OBJECTIVES: This prospective, randomized study aimed to compare the analgesic effects of acetaminophen, diclofenac and hyoscine-N-butylbromide (HnBB) in cases of second trimester pregnancy termination. METHODS: In 60 women with indications for second trimester pregnancy termination, three analgesic agents were randomized into three groups: group 1, acetaminophen; group 2, diclofenac; and group 3, HnBB. A visual analog scale (VAS) used for the evaluation of pain perception. The primary outcome of the study was mean VAS score during the procedure and last VAS score before the completion of termination. The secondary outcomes were the induction-to-abortion interval, the percentage of aborted cases within the first 24 h and finally the need for parenteral analgesia. RESULTS: Demographic characteristics were similar among the groups. The mean VAS and last VAS scores before termination did not differ among the groups (p = 0.3 and 0.2, respectively). The need for parenteral analgesia did not differ among the groups (p = 0.3). Although a shorter induction-to-abortion interval and greater number of cases with successful termination before 24 h were found in the HnBB group, the differences were not statistically significant (p = 0.6 and 0.5, respectively). CONCLUSIONS: Our study did not demonstrate a difference in pain perception among second trimester pregnancy termination cases using acetaminophen, diclofenac and HnBB. PMID- 26823242 TI - Boiling Frogs and Burning Out. PMID- 26823241 TI - The ontogeny of nasal shape: An analysis of sexual dimorphism in a longitudinal sample. AB - OBJECTIVES: Potential integration between the nasal region and noncranial components of the respiratory system has significant implications for understanding determinants of craniofacial variation. There is increasing evidence that sexual dimorphism in body size and associated male-female differences in energetically relevant variables influence the development of the nasal region. To better understand this relationship, we examined the ontogeny of sexual dimorphism in nasal shape using a longitudinal series of lateral cephalograms. METHODS: We collected a series of two dimensional coordinate landmark data from n = 20 males and n = 18 females from 3.0 to 20.0+ years of age totaling n = 290 observations across nine age groups. First, we tested whether there are sex differences in the nasal shape related to ontogenetic increases in body size (i.e., sitting height). Additionally, we examined whether there are male-female differences in patterns of nonallometric variation in nasal shape. Next, we tested whether there are sex differences in the strength of integration between the nasal region and other aspects of the facial skeleton. RESULTS: Our results indicate that there are a number of similarities in patterns of morphological variation in the nasal region between males and females. However, as sitting height increases males exhibit a disproportionate increase in nasal region height that is not present in the female sample. Moreover, the male nasal region is less integrated with the surrounding facial skeleton when compared to the female sample. CONCLUSIONS: These results are consistent with the hypothesis that sex differences in nasal development are associated with male-female differences in energetically relevant variables. PMID- 26823243 TI - Integrating primary mental health care and mental health promotion. PMID- 26823244 TI - Stroke prevention in atrial fibrillation: we can do better. PMID- 26823245 TI - The Accessible Information Standard: action and reaction. PMID- 26823246 TI - Fighting about conflict of interest: where should the balance lie? PMID- 26823247 TI - Special needs for us or assess and treat all patients as individuals? PMID- 26823248 TI - Assisted dying: the pressure for change. PMID- 26823250 TI - Access to primary care. PMID- 26823249 TI - Euthanasia: providing optimal terminal care. PMID- 26823251 TI - Been there, done that, bought the T-shirt. PMID- 26823252 TI - Stuck song syndrome: musical obsessions - when to look for OCD. PMID- 26823254 TI - Why patients and doctors should watch Inside Out. PMID- 26823253 TI - Keep an eye on the SSRI: help avoid possible sight-threatening adverse events. PMID- 26823255 TI - Compassion, continuity and caring: a new GP's perspective. PMID- 26823256 TI - Are contemporary mindfulness-based interventions unethical? PMID- 26823257 TI - Yonder: Injectable contraception, back pain, family-centred care, and diet soft drinks. PMID- 26823260 TI - Evidence and judgement. PMID- 26823261 TI - Green fingers and clear minds: prescribing 'care farming' for mental illness. PMID- 26823262 TI - Enablers and barriers for engaged, informed individuals and carers: left wall of the House of Care framework. PMID- 26823264 TI - Clarifying empathy: the first step to more humane clinical care. PMID- 26823263 TI - Barriers to effective management of type 2 diabetes in primary care: qualitative systematic review. AB - BACKGROUND: Despite the availability of evidence-based guidance, many patients with type 2 diabetes do not achieve treatment goals. AIM: To guide quality improvement strategies for type 2 diabetes by synthesising qualitative evidence on primary care physicians' and nurses' perceived influences on care. DESIGN AND SETTING: Systematic review of qualitative studies with findings organised using the Theoretical Domains Framework. METHOD: Databases searched were MEDLINE, Embase, CINAHL, PsycInfo, and ASSIA from 1980 until March 2014. Studies included were English-language qualitative studies in primary care of physicians' or nurses' perceived influences on treatment goals for type 2 diabetes. RESULTS: A total of 32 studies were included: 17 address general diabetes care, 11 glycaemic control, three blood pressure, and one cholesterol control. Clinicians struggle to meet evolving treatment targets within limited time and resources, and are frustrated with resulting compromises. They lack confidence in knowledge of guidelines and skills, notably initiating insulin and facilitating patient behaviour change. Changing professional boundaries have resulted in uncertainty about where clinical responsibility resides. Accounts are often couched in emotional terms, especially frustrations over patient compliance and anxieties about treatment intensification. CONCLUSION: Although resources are important, many barriers to improving care are amenable to behaviour change strategies. Improvement strategies need to account for differences between clinical targets and consider tailored rather than 'one size fits all' approaches. Training targeting knowledge is necessary but insufficient to bring about major change; approaches to improve diabetes care need to delineate roles and responsibilities, and address clinicians' skills and emotions around treatment intensification and facilitation of patient behaviour change. PMID- 26823265 TI - Redefining quality: valuing the role of the GP in managing uncertainty. PMID- 26823266 TI - Obstructive sleep apnoea: is it moving into primary care? PMID- 26823267 TI - Identifying depression among adolescents using three key questions: a validation study in primary care. AB - BACKGROUND: Depression in adolescents is a serious psychiatric illness. GPs play an important role in identifying adolescents with depression and those at risk of developing depression. Few validated tools are suitable for identifying adolescent depression in general practice. AIM: To determine if three verbally asked key questions are valid for identifying depression in adolescents. DESIGN AND SETTING: A cross-sectional, general practice multicentre, validation study was conducted in Oslo, Norway, and Aarhus, Denmark. METHOD: A total of 294 adolescents answered three verbally asked key questions followed by a Composite International Diagnostic Interview (CIDI) for psychiatric diagnosis. Inclusion criteria were age (14-16 years) and fluency in the Norwegian or Danish language. The primary outcome was ROC curve statistics in terms of sensitivity and specificity, predictive values, and likelihood ratios of the three key questions. Secondary outcomes were Loevinger's H, Cronbach's alpha, and prevalence of depression. RESULTS: The three key questions met the criteria for construct and criterion validity for detecting depression among the adolescents. ROC curve statistics for the three key questions demonstrated an AUC of 0.79 for the answer 'yes' to either screening question and of 0.73 for the answer 'yes' to the help question. The positive predictive value was 31% and the negative predictive value was 97%. CONCLUSION: The three key questions are useful for identifying depression in adolescents in primary health care. PMID- 26823268 TI - Usefulness of PHQ-9 in primary care to determine meaningful symptoms of low mood: a qualitative study. AB - BACKGROUND: Self-administered questionnaires, such as the Patient Health Questionnaire (PHQ-9), are regularly used in clinical practice to guide prescribing or to measure recovery and response to treatment. There are concerns that patients are not all interpreting the questionnaire items in the same way. Cognitive interviewing is a research technique that identifies 'interpretative measurement error' (IME). IME is distinct from traditional components of measurement error, such as not reading the question as worded, or recording answers inaccurately. AIM: To use cognitive interviewing techniques to explore patterns in answer mapping and comprehension of the PHQ-9 questionnaire to ascertain whether the measure captures meaningful symptoms of low mood. DESIGN AND SETTING: Qualitative study using cognitive interviewing techniques and card sorting in six GP practices in Bristol. METHOD: The study recruited 18 participants at the point of entry to a longitudinal primary care depression cohort study, PANDA (the indications for Prescribing ANtiDepressants that will leAd to a clinical benefit). Participants were interviewed 2, 4, and 6 weeks after their baseline visit. Cognitive interviews were digitally recorded. Analysis used the digital audio file, rather than verbatim transcripts, as it retained important features needed for analyses. RESULTS: Cognitive interviewing revealed that items on the PHQ-9 are interpreted in a range of ways, that patients often cannot 'fit' their experience into the response options, and therefore often feel the questionnaire is misrepresenting their experience of meaningful symptoms of low mood. CONCLUSION: The PHQ-9 may be missing the presence and/or intensity of certain symptoms that are meaningful to patients. Clinicians should adopt caution when using it. PMID- 26823270 TI - Experiences of suicide bereavement: a qualitative study exploring the role of the GP. AB - BACKGROUND: Suicide is a major public health issue. GPs are often on the front line in responding to a suicide. They are called on to support individuals and families in the aftermath of suicide yet there is a dearth of research, particularly from patients' perspectives, on how to provide optimal care for those grieving a suicide in the primary care setting. AIM: To improve GP management of suicide bereavement by exploring the lived experiences of affected individuals, focusing on the GP's involvement in the grief process. DESIGN AND SETTING: A qualitative approach was adopted using focus group interviews with individuals from suicide bereavement support groups at three locations across Ireland. METHOD: Support groups were contacted by letter. Fifteen interested participants formed three focus groups. Interviews were audiorecorded and transcripts were analysed thematically using the framework method. RESULTS: Three major themes dominated: the need for acknowledgement - of the loss and of the lived life of the deceased; the role of stigma in the aftermath of the loss; and the need for proactive provision of direction and support during the grief journey. The GP was identified as ideally positioned in the community to cater for the needs of the bereaved. CONCLUSION: Suicide can result in prolonged, complex grief generating specific patient needs. Stigma may function as a barrier to help seeking. The GP should consider initiating contact with the bereaved. Recommendations have been made to support GPs in their care of the suicide bereaved. PMID- 26823269 TI - Efficacy of two interventions on the discontinuation of benzodiazepines in long term users: 36-month follow-up of a cluster randomised trial in primary care. AB - BACKGROUND: Primary care interventions that promote cessation of benzodiazepine (BZD) use in long-term users are effective at 1 year, but their efficacy at 3 years is uncertain. AIM: To assess the 3-year efficacy of two primary care interventions delivered by GPs on cessation of BZD use in long-term users. DESIGN AND SETTING: Multicentre, three-arm, cluster randomised, controlled trial, with random allocation at the GP level. METHOD: Seventy-five GPs and 532 patients were randomly allocated to three groups: usual care (control), structured intervention with stepped-dose reduction and follow-up visits (SIF), or structured intervention with written stepped-dose reduction (SIW). The primary outcome was BZD use at 36 months. RESULTS: At 36 months, 66/168 patients (39.2%) in the SIW group, 79/191 patients (41.3%) in the SIF group, and 45/173 patients (26.0%) in the control group had discontinued BZD use. The relative risks (RR) adjusted by cluster were 1.51 (95% CI = 1.10 to 2.05; P = 0.009) in the SIW group and 1.59 (95% CI = 1.15 to 2.19; P = 0.005) in the SIF group. A total of 131/188 patients (69.7%) who successfully discontinued BZD use at 12 months remained abstinent at 36 months. The groups showed no significant differences in anxiety, depression, or sleep dissatisfaction at 36 months. CONCLUSION: The interventions were effective on cessation of BZD use; most patients who discontinued at 12 months remained abstinent at 3 years. Discontinuation of BZD use did not have a significant effect on anxiety, depression, or sleep quality. PMID- 26823271 TI - Mindfulness-based stress reduction for GPs: results of a controlled mixed methods pilot study in Dutch primary care. AB - BACKGROUND: Burnout is highly prevalent in GPs and can have a negative influence on their wellbeing, performance, and patient care. Mindfulness-based stress reduction (MBSR) may be an effective intervention to decrease burnout symptoms and increase wellbeing. AIM: To gain insight into the feasibility and effectiveness of MBSR on burnout, empathy, and (work-related) wellbeing in GPs. DESIGN AND SETTING: A mixed methods pilot study, including a waiting list controlled pre-/post-study and a qualitative study of the experiences of participating GPs in the Netherlands. METHOD: Participants were sent questionnaires assessing burnout, work engagement, empathy, and mindfulness skills, before and at the end of the MBSR training/waiting period. Qualitative data on how GPs experienced the training were collected during a plenary session and with evaluation forms at the end of the course. RESULTS: Fifty Dutch GPs participated in this study. The MBSR group reported a greater decrease in depersonalisation than the control group (adjusted difference -1.42, 95% confidence interval [CI] = -2.72 to -0.21, P = 0.03). Dedication increased more significantly in the MBSR group than in the control group (adjusted difference 2.17, 95% CI = 0.51 to 3.83, P = 0.01). Mindfulness skills increased significantly in the MBSR group compared with the control group (adjusted difference 6.90, 95% CI = 1.42 to 12.37, P = 0.01). There was no significant change in empathy. The qualitative data indicated that the MBSR course increased their wellbeing and compassion towards themselves and others, including their patients. CONCLUSION: The study shows that MBSR for GPs is feasible and might result in fewer burnout symptoms and increased work engagement and wellbeing. However, an adequately powered randomised controlled trial is needed to confirm the study's findings. PMID- 26823272 TI - Nutrition in acute pancreatitis: a critical review. AB - Severe acute pancreatitis poses unique nutritional challenges. The optimal nutritional support in patients with severe acute pancreatitis has been a subject of debate for decades. This review provides a critical review of the available literature. According to current literature, enteral nutrition is superior to parenteral nutrition, although several limitations should be taken into account. The optimal route of enteral nutrition remains unclear, but normal or nasogastric tube feeding seems safe when tolerated. In patients with predicted severe acute pancreatitis an on-demand feeding strategy is advised and when patients do not tolerate an oral diet after 72 hours, enteral nutrition can be started. The use of supplements, both parenteral as enteral, are not recommended. Optimal nutritional support in severe cases often requires a tailor-made approach with day-to-day evaluation of its effectiveness. PMID- 26823273 TI - PdxH proteins of mycobacteria are typical members of the classical pyridoxine/pyridoxamine 5'-phosphate oxidase family. AB - Pyridoxal 5'-phosphate (PLP) biosynthesis is essential for the survival and virulence of Mycobacterium tuberculosis (Mtb). PLP functions as a cofactor for 58 putative PLP-binding proteins encoded by the Mtb genome and could also act as a potential antioxidant. De novo biosynthesis of PLP in Mtb takes place through the 'deoxyxylulose 5'-phosphate (DXP)-independent' pathway, whereas PdxH enzymes, possessing pyridoxine/pyridoxamine 5'-phosphate oxidase (PNPOx) activity, are involved in the PLP salvage pathway. In this study, we demonstrate that the annotated PdxH enzymes from various mycobacterial species are bona fide members of the classical PNPOx enzyme family, capable of producing PLP using both pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP) substrates. PMID- 26823274 TI - Influence of Equatorial CH???O Interactions on Secondary Kinetic Isotope Effects for Methyl Transfer. AB - DFT calculations for methyl cation complexed within a constrained cage of water molecules permit the controlled manipulation of the "axial" donor/acceptor distance and the "equatorial" distance to hydrogen-bond acceptors. The kinetic isotope effect k(CH3)/k(CT3) for methyl transfer within a cage with a short axial distance becomes less inverse for shorter equatorial C???O distances: a decrease of 0.5 A results in a 3 % increase at 298 K. Kinetic isotope effects in AdoMet dependent methyltransferases may be m?odulated by CH???O hydrogen bonding, and factors other than axial compression may contribute, at least partially, to recently reported isotope-effect variations for catechol-O-methyltransferase and its mutant structures. PMID- 26823275 TI - Emergency medical admissions at weekends are older and more functionally dependent than those admitted on weekdays. PMID- 26823276 TI - Once-weekly prophylactic treatment vs. on-demand treatment with nonacog alfa in patients with moderately severe to severe haemophilia B. AB - INTRODUCTION: Limited data are available on optimal prophylaxis regimens of factor IX (FIX) replacements for patients with haemophilia B. AIM: This multicentre, open-label study evaluated the efficacy and safety of once-weekly prophylaxis with nonacog alfa compared with on-demand treatment in adolescent and adult patients. METHODS: Males aged 12-65 years with moderately severe to severe haemophilia B (FIX:C <= 2%) were eligible for enrolment. Patients received on demand treatment for 26 weeks, followed by once-weekly prophylaxis of 100 IU kg( 1) for 52 weeks. The primary efficacy end point was the annualized bleeding rate (ABR). Secondary end points included response to on-demand treatment, the number of infusions used to treat bleeding events, and the incidence of less-than expected therapeutic effect (LETE). FIX:C was measured on day 1 and at weeks 26 and 78. RESULTS: Mean (+/-SD) ABR was lower during prophylaxis vs. on-demand treatment [3.6 (+/-4.6) vs. 32.9 (+/-17.4) events, respectively; P < 0.0001]. The majority (88.4%) of bleeding events had excellent or good responses upon the first infusion; 82.1% of events responded to the first infusion. No incident of LETE occurred. No thrombotic events or FIX inhibitors were reported. Eight of 17 FIX:C approximately 1 week after dosing were >2 IU dL(-1) (min-max of 2.13-10.39 IU dL(-1) ). CONCLUSIONS: Once-weekly prophylaxis of 100 IU kg(-1) was associated with lower ABR compared with on-demand treatment in adolescents and adults with moderately severe to severe haemophilia B. Once-weekly prophylaxis was well tolerated, with a similar safety profile as that reported during the on-demand treatment period. Residual FIX:C may be supportive of effectiveness. PMID- 26823277 TI - Non-falciparum malaria infections in pregnant women in West Africa. AB - BACKGROUND: Non-Plasmodium falciparum malaria infections are found in many parts of sub-Saharan Africa but little is known about their importance in pregnancy. METHODS: Blood samples were collected at first antenatal clinic attendance from 2526 women enrolled in a trial of intermittent screening and treatment of malaria in pregnancy (ISTp) versus intermittent preventive treatment (IPTp) conducted in Burkina Faso, The Gambia, Ghana and Mali. DNA was extracted from blood spots and tested for P. falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale using a nested PCR test. Risk factors for a non-falciparum malaria infection were investigated and the influence of these infections on the outcome of pregnancy was determined. RESULTS: P. falciparum infection was detected frequently (overall prevalence by PCR: 38.8 %, [95 % CI 37.0, 40.8]), with a prevalence ranging from 10.8 % in The Gambia to 56.1 % in Ghana. Non-falciparum malaria infections were found only rarely (overall prevalence 1.39 % [95 % CI 1.00, 1.92]), ranging from 0.17 % in the Gambia to 3.81 % in Mali. Ten non falciparum mono-infections and 25 mixed falciparum and non-falciparum infections were found. P. malariae was the most frequent non-falciparum infection identified; P. vivax was detected only in Mali. Only four of the non-falciparum mono-infections were detected by microscopy or rapid diagnostic test. Recruitment during the late rainy season and low socio-economic status were associated with an increased risk of non-falciparum malaria as well as falciparum malaria. The outcome of pregnancy did not differ between women with a non-falciparum malaria infection and those who were not infected with malaria at first ANC attendance. CONCLUSIONS: Non-falciparum infections were infrequent in the populations studied, rarely detected when present as a mono-infection and unlikely to have had an important impact on the outcome of pregnancy in the communities studied due to the small number of women infected with non-falciparum parasites. PMID- 26823278 TI - Evaporative Self-Assembly of Gold Nanorods into Macroscopic 3D Plasmonic Superlattice Arrays. AB - Millimeter-scale 3D superlattice arrays composed of dense, regular, and vertically aligned gold nanorods are fabricated by evaporative self-assembly. The regular organization of the gold nanorods into a macroscopic superlattice enables the production of a plasmonic substrate with excellent sensitivity and reproducibility, as well as reliability in surface-enhanced Raman scattering. The work bridges the gap between nanoscale materials and macroscopic applications. PMID- 26823279 TI - Sequential activation of the intrarenal renin-angiotensin system in the progression of hypertensive nephropathy in Goldblatt rats. AB - The intrarenal renin-angiotensin system (RAS) has an important role in generating and maintaining hypertension in two-kidney, one-clip (2K1C) rats. This study evaluated how various intrarenal RAS components contributed to hypertension not only in the maintenance period (5w; 5 wk after operation) but also earlier (2w; 2 wk after operation). We inserted a 2.5-mm clip into the left renal artery of Sprague-Dawley rats and euthanized them at 2w and 5w following the operation. Systolic blood pressure increased within 1 wk after the operation, and left ventricular hypertrophy occurred in 2K1C rats. At 2w, juxtaglomerular apparatus (JGA) and collecting duct (CD) renin increased in clipped kidney (CK) of 2K1C rats. The tubular angiotensin I-converting enzyme (ACE) was not changed, but peritubular ACE2 decreased in nonclipped kidney (NCK) and CK of 2K1C rats. At 5w, ACE and CD renin were enhanced, and ACE2 was still lessened in both kidneys of 2K1C rats. However, plasma renin activity (PRA) was not different from that in sham rats. In proximal tubules of CK, the ANG II type 1 receptor (AT1R) was not suppressed, but the Mas receptor (MasR) was reduced; thus the AT1R/MasR ratio was elevated. Although hypoxic change in CK could not be excluded, the JGA renin of CK and CD renin in both kidneys was highly expressed independent of time. Peritubular ACE2 changed in the earlier period, and uninhibited AT1R in proximal tubules of CK was presented in the maintenance period. In 2K1C rats, attenuated ACE2 seems to contribute to initiating hypertension while upregulated ACE in combination with unsuppressed AT1R may have a key role in maintaining hypertension. PMID- 26823280 TI - B7-1 biomarker bites the dust. PMID- 26823281 TI - Acquired resistance to rechallenge injury after acute kidney injury in rats is associated with cell cycle arrest in proximal tubule cells. AB - Rats that have recovered from severe proximal tubule (PT) injury induced by uranyl acetate (UA), a toxic stimulus, developed resistance to subsequent UA treatment. We investigated cell cycle status and progression in PT cells in relation to this acquired resistance. Fourteen days after pretreatment with saline (vehicle group) or UA [acute kidney injury (AKI) group], rats were injected with UA or lead acetate (a proliferative stimulus). Cell cycle status (G0/G1/S/G2/M) was analyzed by flow cytometry. The expression of cell cycle markers, cyclin-dependent kinase inhibitors, and phenotypic markers were examined by immunohistochemistry. Cell cycle status in PT cells in the AKI group was comparable to those of the vehicle group. However, more early G1-phase cells (cyclin D1- or Ki67-) and p21+ or p27+ cells were found in the PT of the AKI group than in that of the vehicle group. UA induced G1 arrest and inhibited S phase progression with earlier dedifferentiation and less apoptosis in PT cells of the AKI group. Lead acetate induced proliferation without dedifferentiation but with delayed G0-G1 transition and inhibited S phase progression in PT cells in the AKI group. Sustained p21 and increased p27 expression in PT cells were found in the AKI group in response to UA and lead acetate. PT cells in the AKI group inhibited cell cycle progression by enhanced G1 arrest, probably via p21/p27 modulation as an injury or proliferation response, resulting in cytoresistance to rechallenge injury. PMID- 26823283 TI - An immunoassay for urinary extracellular vesicles. AB - Although nanosized urinary extracellular vesicles (uEVs) are increasingly used for biomarker discovery, their isolation currently relies on time-consuming techniques hindering high-throughput application. To navigate this problem, we designed an immunoassay to isolate, quantify, and normalize uEV proteins. The uEV immunoassay consists of a biotinylated CD9 antibody to isolate uEVs, an antibody against the protein of interest, and two conjugated antibodies to quantify the protein of interest and CD9. As a proof of principle, the immunoassay was developed to analyze the water channel aquaporin-2 (AQP2) and the sodium-chloride cotransporter (NCC). CD9 was used as a capture antibody because immunoprecipitation showed that anti-CD9 antibody, but not anti-CD63 antibody, isolated AQP2 and NCC. CD9 correlated strongly with urine creatinine, allowing CD9 to be used for normalization of spot urines. The uEV immunoassay detected AQP2 and NCC with high sensitivity, low coefficients of variance, and stability in dilution series. After water loading in healthy subjects, the uEV immunoassay detected decreases in AQP2 and NCC equally well as the traditional method using ultracentrifugation and immunoblot. The uEV immunoassay also reliably detected lower and higher AQP2 or NCC levels in uEVs from patients with pathological water or salt reabsorption, respectively. In summary, we report a novel approach to analyze uEVs that circumvents existing isolation and normalization issues, requires small volumes of urine, and detects anticipated changes in physiological responses and clinical disorders. PMID- 26823282 TI - Modulation of the myogenic mechanism: concordant effects of NO synthesis inhibition and O2- dismutation on renal autoregulation in the time and frequency domains. AB - Renal blood flow autoregulation was investigated in anesthetized C57Bl6 mice using time- and frequency-domain analyses. Autoregulation was reestablished by 15 s in two stages after a 25-mmHg step increase in renal perfusion pressure (RPP). The renal vascular resistance (RVR) response did not include a contribution from the macula densa tubuloglomerular feedback mechanism. Inhibition of nitric oxide (NO) synthase [N(G)-nitro-l-arginine methyl ester (l-NAME)] reduced the time for complete autoregulation to 2 s and induced 0.25-Hz oscillations in RVR. Quenching of superoxide (SOD mimetic tempol) during l-NAME normalized the speed and strength of stage 1 of the RVR increase and abolished oscillations. The slope of stage 2 was unaffected by l-NAME or tempol. These effects of l-NAME and tempol were evaluated in the frequency domain during random fluctuations in RPP. NO synthase inhibition amplified the resonance peak in admittance gain at 0.25 Hz and markedly increased the gain slope at the upper myogenic frequency range (0.06 0.25 Hz, identified as stage 1), with reversal by tempol. The slope of admittance gain in the lower half of the myogenic frequency range (equated with stage 2) was not affected by l-NAME or tempol. Our data show that the myogenic mechanism alone can achieve complete renal blood flow autoregulation in the mouse kidney following a step increase in RPP. They suggest also that the principal inhibitory action of NO is quenching of superoxide, which otherwise potentiates dynamic components of the myogenic constriction in vivo. This primarily involves the first stage of a two-stage myogenic response. PMID- 26823284 TI - Effect of type II diabetes on male rat bladder contractility. AB - Type II diabetes is the most prevalent form of diabetes. One of the primary complications of diabetes that significantly affects quality of life is bladder dysfunction. Many studies on diabetic bladder dysfunction have been performed in models of type I diabetes; however, few have been performed in animal models of type II diabetes. Using the Zucker Diabetic Fatty (ZDF) rat model of type II diabetes, we examined the contractility and sensitivity of bladder smooth muscle in response to mediators of depolarization-induced contraction, muscarinic receptor-mediated contraction, ATP-induced contraction, and neurogenic contraction. Studies were performed at 16 and 27 wk of age to monitor the progression of diabetic bladder dysfunction. Voiding behavior was also quantified. The entire bladder walls of diabetic rats were hypertrophied compared with that of control rats. Contractility and sensitivity to carbachol and ATP were increased at 27 wk in bladder smooth muscle strips from diabetic rats, suggesting a compensated state of diabetic bladder dysfunction. Purinergic signaling was increased in response to exogenous ATP in bladders from diabetic animals; however, the purinergic component of neurogenic contractions was decreased. The purinergic component of neurogenic contraction was reduced by P2X receptor desensitization, but was unchanged by P2X receptor inhibition in diabetic rats. Residual and tetrodotoxin-resistant components of neurogenic contraction were increased in bladder strips from diabetic animals. Overall, our results suggest that in the male ZDF rat model, the bladder reaches the compensated stage of function by 27 wk and has increased responsiveness to ATP. PMID- 26823285 TI - Nedd4-2 but not Nedd4-1 is critical for protein kinase C-regulated ubiquitination, expression, and transport activity of human organic anion transporter 1. AB - Human organic anion transporter 1 (hOAT1) expressed at the membrane of the kidney proximal tubule cells mediates the body disposition of a diverse array of clinically important drugs, including anti-HIV therapeutics, antitumor drugs, antibiotics, antihypertensives, and antiinflammatories. Therefore, understanding the regulation of hOAT1 will provide significant insights into kidney function and dysfunction. We previously established that hOAT1 transport activity is inhibited by activation of protein kinase C (PKC) through accelerating hOAT1 internalization from cell surface into intracellular endosomes and subsequent degradation. We further established that PKC-induced hOAT1 ubiquitination is an important step preceding hOAT1 internalization. In the current study, we identified two closely related E3 ubiquitin ligases, neural precursor cell expressed, developmentally downregulated 4-1 and 4-2 (Nedd4-1 and Nedd4-2), as important regulators for hOAT1: overexpression of Nedd4-1 or Nedd4-2 enhanced hOAT1 ubiquitination, reduced the hOAT1 amount at the cell surface, and suppressed hOAT1 transport activity. In further exploring the relationship among PKC, Nedd4-1, and Nedd4-2, we discovered that PKC-dependent changes in hOAT1 ubiquitination, expression, and transport activity were significantly blocked in cells transfected with the ligase-dead mutant of Nedd4-2 (Nedd4-2/C821A) or with Nedd4-2-specific siRNA to knockdown endogenous Nedd4-2 but not in cells transfected with the ligase-dead mutant of Nedd4-1 (Nedd4-1/C867S) or with Nedd4 1-specific siRNA to knockdown endogenous Nedd4-1. In conclusion, this is the first demonstration that both Nedd4-1 and Nedd4-2 are important regulators for hOAT1 ubiquitination, expression, and function. Yet they play distinct roles, as Nedd4-2 but not Nedd4-1 is a critical mediator for PKC-regulated hOAT1 ubiquitination, expression, and transport activity. PMID- 26823286 TI - Obesity is associated with decreased lung compliance and hypercapnia during robotic assisted surgery. AB - Robotic assisted surgery (RAS) represents a great challenge for anesthesiology due to the increased intraabdomial pressures required for surgical optimal approach. The changes in lung physiology are difficult to predict and require fast decision making in order to prevent altered gas exchange. The aim of this study was to document the combined effect of patient physical status, medical history and intraoperative position during RAS on lung physiology and to determine perioperative risk factors for hypercapnia. We prospectively analyzed 62 patients who underwent elective RAS. Age, co-morbidities and body mass index (BMI) were recorded before surgery. Ventilatory parameters and arterial blood gas analysis were determined before induction of anesthesia, after tracheal intubation and on an hourly basis until the end of surgery. In RAS, the induction of pneumoperitoneum was associated with a significant decrease in lung compliance from a mean of 42.5-26.7 ml cm H2O-1 (p = 0.001) and an increase in plateau pressure from a mean of 16.1 mmHg to a mean of 23.6 mmHg (p = 0.001). Obesity, demonstrated by a BMI over 30, significantly correlates with a decrease in lung compliance after induction of anesthesia (p = 0.001). A significant higher increase in arterial CO2 tension was registered in patients undergoing RAS in steep Trendelenburg position (p = 0.05), but no significant changes in end-tidal CO2 were recorded. A higher arterial to end-tidal CO2 tension gradient was observed in patients with a BMI > 30 (p < 0.001). In conclusion, patients' physical status, especially obesity, represents the main risk factor for decreased lung compliance during RAS and patient positioning in either Trendelenburg or steep Trendelenburg during surgery has limited effects on respiratory physiology. PMID- 26823287 TI - Response from author to the editor. PMID- 26823288 TI - Prevalence and characterization of extended-spectrum beta-lactamases producing Enterobacteriaceae in healthy children and associated risk factors. AB - BACKGROUND: Community acquired infections due to extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-PE) had been increased. The fecal flora of children in the community represents a huge potential reservoir for ESBLs which are located on highly transmissible plasmids. This study examined the prevalence of ESBL-PE fecal carriage, antimicrobial susceptibility pattern, possible risk factors, and characterized the genes encoding these ESBL enzymes in Lebanese children community. METHODS: A total of 125 rectal swabs were taken from healthy children aged from 1 to 5 years. Detection of ESBLs was carried out using combination-disc method test and multiplex PCR. A questionnaire concerning child's lifestyle and risk factors for ESBL carriage was illustrated. RESULTS: Thirty-one of 125 participants (24.8 %) carried ESBL-PE. Regular consumption of meat, and chicken were significantly associated with high carriage rate of ESBL PE, while dairy products (milk, yogurt, cheese) association was non-significant. Intimate hygiene habits were found also affecting the carriage rate. Multiple bla genes were the most common, 48.4 % (15/31) of ESBL-PE carried both bla CTX-M and bla TEM, and 22.6 % (7/31) carried bla CTX-M, bla SHV, and bla TEM, 29 % (9) carried bla CTX-M only. Concerning CTX-M-types, CTX-M-9 was the most predominant (24/31) and mostly in combination with CTX-M-15 type. CONCLUSION: High rate of colonization in healthy children with ESBL-PE was observed, regular consumption of dietary products from animal source (meat or chicken) were associated with this colonization in the community in non-hospitalized children. To our best knowledge it is the first study about regular consumption of dairy product as a risk factor for ESBL-PE community carriage, the first data about the carriage rate of ESBL-PE in community children in Lebanon and Middle East, and for the wide dissemination of CTX-M-9 type in this population. PMID- 26823289 TI - E2F function in muscle growth is necessary and sufficient for viability in Drosophila. AB - The E2F transcription factor is a key cell cycle regulator. However, the inactivation of the entire E2F family in Drosophila is permissive throughout most of animal development until pupation when lethality occurs. Here we show that E2F function in the adult skeletal muscle is essential for animal viability since providing E2F function in muscles rescues the lethality of the whole-body E2F deficient animals. Muscle-specific loss of E2F results in a significant reduction in muscle mass and thinner myofibrils. We demonstrate that E2F is dispensable for proliferation of muscle progenitor cells, but is required during late myogenesis to directly control the expression of a set of muscle-specific genes. Interestingly, E2f1 provides a major contribution to the regulation of myogenic function, while E2f2 appears to be less important. These findings identify a key function of E2F in skeletal muscle required for animal viability, and illustrate how the cell cycle regulator is repurposed in post-mitotic cells. PMID- 26823290 TI - Laquinimod dampens hyperactive cytokine production in Huntington's disease patient myeloid cells. AB - Huntington's disease (HD) is a neurodegenerative condition characterized by pathology in the brain and peripheral tissues. Hyperactivity of the innate immune system, due in part to NFkappaB pathway dysregulation, is an early and active component of HD. Evidence suggests targeting immune disruption may slow disease progression. Laquinimod is an orally active immunomodulator that down-regulates proinflammatory cytokine production in peripheral blood mononuclear cells, and in the brain down-regulates astrocytic and microglial activation by modulating NFkappaB signalling. Laquinimod had beneficial effects on inflammation, brain atrophy and disease progression in multiple sclerosis (MS) in two phase III clinical trials. This study investigated the effects of laquinimod on hyperactive proinflammatory cytokine release and NFkappaB signalling in HD patient myeloid cell cultures. Monocytes from manifest (manHD) and pre-manifest (preHD) HD gene carriers and healthy volunteers (HV) were treated with laquinimod and stimulated with lipopolysaccharide. After 24 h pre-treatment with 5 MUM laquinimod, manHD monocytes released lower levels of IL-1beta, IL-5, IL-8, IL-10, IL-13 and TNFalpha in response to stimulation. PreHD monocytes released lower levels of IL 8, IL-10 and IL-13, with no reduction observed in HV monocytes. The effects of laquinimod on dysfunctional NFkappaB signalling in HD was assessed by inhibitor of kappa B (IkappaB) degradation kinetics, nuclear translocation of NFkappaB and interactions between IkappaB kinase (IKK) and HTT, in HD myeloid cells. No differences were observed between laquinimod-treated and untreated conditions. These results provide evidence that laquinimod dampens hyper-reactive cytokine release from manHD and preHD monocytes, with a much reduced effect on HV monocytes. Evidence suggests targeting CNS and peripheral immune disruption may slow Huntington's disease (HD) neurodegenerative processes. The effects of laquinimod, an orally active immunomodulator, on hyperactive cytokine release and dysfunctional NFkappaB signalling in stimulated myeloid cell cultures from pre manifest and manifest HD gene carriers and healthy volunteers were investigated. Laquinimod dampened cytokine release but did not impact NFkappaB signalling. Read the Editorial Highlight for this article on page 670. PMID- 26823291 TI - Palliative care research centre's move into social media: constructing a framework for ethical research, a consensus paper. AB - BACKGROUND: Social media (SM) have altered the way we live and, for many, the way we die. The information available on even the rarest conditions is vast. Free from restrictions of mobility, time and distance, SM provides a space for people to share experiences of illness, death and dying, and potentially benefit from the emotional and practical support of others n similar positions. The communications that take place in these spaces also create large amounts of 'data' which, for any research centre, cannot be ignored. However, for a palliative care research centre the use of this 'data' comes with specific ethical dilemmas. METHODS: This paper details the process that we, as a research, went through in constructing a set of ethical guidelines by which to work. This involved conducting two consensus days; one with researchers from within the centre, and one with the inclusion of external researchers with a specific interest in SM. RESULTS: The primary themes that emerged from the consensus meetings includes; SM as a public or private space; the status of open and closed groups; the use of historical data; recruiting participants and obtaining informed consent and problems of anonymity associated with dissemination. CONCLUSIONS: These are the themes that this paper will focus on prior to setting out the guidelines that we subsequently constructed. PMID- 26823292 TI - Integrated optofluidic-microfluidic twin channels: toward diverse application of lab-on-a-chip systems. AB - Optofluidics, which integrates microfluidics and micro-optical components, is crucial for optical sensing, fluorescence analysis, and cell detection. However, the realization of an integrated system from optofluidic manipulation and a microfluidic channel is often hampered by the lack of a universal substrate for achieving monolithic integration. In this study, we report on an integrated optofluidic-microfluidic twin channels chip fabricated by one-time exposure photolithography, in which the twin microchannels on both surfaces of the substrate were exactly aligned in the vertical direction. The twin microchannels can be controlled independently, meaning that fluids could flow through both microchannels simultaneously without interfering with each other. As representative examples, a tunable hydrogel microlens was integrated into the optofluidic channel by femtosecond laser direct writing, which responds to the salt solution concentration and could be used to detect the microstructure at different depths. The integration of such optofluidic and microfluidic channels provides an opportunity to apply optofluidic detection practically and may lead to great promise for the integration and miniaturization of Lab-on-a-Chip systems. PMID- 26823293 TI - Response to: "Near-peer driven dissection selective: A primer to the medical school anatomy course". PMID- 26823295 TI - Predictors of Continued Use of Extended-Released Naltrexone (XR-NTX) for Opioid Dependence: An Analysis of Heroin and Non-Heroin Opioid Users in Los Angeles County. AB - Extended-release naltrexone (XR-NTX) is associated with an increased number of opioid-free days, improved adherence rates in substance use disorder treatment programs, and reduced cravings and drug-seeking behaviors. There is little evidence on the predictive associations between baseline characteristics of opioid-dependent patients and XR-NTX utilization. Some studies have demonstrated better pharmacotherapy adherence and/or retention rates among non-heroin opioid users compared to heroin users. This study examines predictive associations between characteristics of patients and XR-NTX utilization, as well as participants' urge to use opiates. Our findings suggest that XR-NTX may contribute to decreases in urges to use among both heroin and non-heroin opioid users. Non-heroin opioid users and heroin users were retained in XR-NTX treatment for comparable periods of time. However, those who identified as homeless, injected opioids (regardless of opioid-type), or were diagnosed with a mental illness were less likely to be retained in treatment with XR-NTX. PMID- 26823294 TI - First-Line Afatinib versus Chemotherapy in Patients with Non-Small Cell Lung Cancer and Common Epidermal Growth Factor Receptor Gene Mutations and Brain Metastases. AB - INTRODUCTION: Metastatic spread to the brain is common in patients with non-small cell lung cancer (NSCLC), but these patients are generally excluded from prospective clinical trials. The studies, phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations (LUX-Lung 3) and a randomized, open-label, phase III study of BIBW 2992 versus chemotherapy as first-line treatment for patients with stage IIIB or IV adenocarcinoma of the lung harbouring an EGFR activating mutation (LUX-Lung 6) investigated first-line afatinib versus platinum-based chemotherapy in epidermal growth factor receptor gene (EGFR) mutation-positive patients with NSCLC and included patients with brain metastases; prespecified subgroup analyses are assessed in this article. METHODS: For both LUX-Lung 3 and LUX-Lung 6, prespecified subgroup analyses of progression-free survival (PFS), overall survival, and objective response rate were undertaken in patients with asymptomatic brain metastases at baseline (n = 35 and n = 46, respectively). Post hoc analyses of clinical outcomes was undertaken in the combined data set (n = 81). RESULTS: In both studies, there was a trend toward improved PFS with afatinib versus chemotherapy in patients with brain metastases (LUX-Lung 3: 11.1 versus 5.4 months, hazard ratio [HR] = 0.54, p = 0.1378; LUX-Lung 6: 8.2 versus 4.7 months, HR = 0.47, p = 0.1060). The magnitude of PFS improvement with afatinib was similar to that observed in patients without brain metastases. In combined analysis, PFS was significantly improved with afatinib versus with chemotherapy in patients with brain metastases (8.2 versus 5.4 months; HR, 0.50; p = 0.0297). Afatinib significantly improved the objective response rate versus chemotherapy in patients with brain metastases. Safety findings were consistent with previous reports. CONCLUSIONS: These findings lend support to the clinical activity of afatinib in EGFR mutation-positive patients with NSCLC and asymptomatic brain metastases. PMID- 26823296 TI - Erythrosis Pigmentosa Peribuccalis in an Adolescent: Dermoscopic Description and Management. AB - Erythrosis pigmentosa peribuccalis is an infrequent condition, with fewer than 35 cases reported in the literature, that affects mainly women. It presents as small papules that form a hyperpigmented plaque around the mouth and nose. Little is known about the etiology of this condition, its dermoscopic characteristics have not been described, and no effective treatment has been reported. We report a 15 year-old girl with this rare dermatosis who was successfully managed with daily calcipotriol, weekly topical ivermectin, and strict photoprotection. We also describe for the first time the dermoscopic findings of this entity. PMID- 26823297 TI - Overcoming barriers to developing and using new vaccines. PMID- 26823298 TI - PED to be made notifiable in Scotland. PMID- 26823299 TI - RSPCA 'shocked' by the scale of dog imports to the UK. PMID- 26823300 TI - APHA scientists recognised for their work during the Ebola crisis. PMID- 26823301 TI - BVA seeks clarity in KPIs in Northern Ireland's TB testing contract. PMID- 26823302 TI - Scottish LPAI outbreak linked to wild birds. PMID- 26823303 TI - New case of HPAI reported in the USA. PMID- 26823304 TI - AHT sets out to create the UK's largest canine genome bank. PMID- 26823305 TI - OIE's new director general sets out its plans. PMID- 26823306 TI - Guidance on assessing the fitness of pigs for transport. PMID- 26823307 TI - Learning about disease surveillance. PMID- 26823308 TI - 'MOTs' to help raise owners' awareness of animals' welfare needs. PMID- 26823309 TI - Investigating whale strandings. PMID- 26823310 TI - Feline calicivirus strain diversity in Europe--the 'star-like' tree. PMID- 26823312 TI - Collecting the evidence for EBVM: who pays? PMID- 26823311 TI - Clinical Decision Making. PMID- 26823313 TI - Mycoplasma hyopneumoniae management in gilts. PMID- 26823314 TI - Excess dietary copper. PMID- 26823315 TI - Routine antibiotic dry cow therapy. PMID- 26823316 TI - Movement of game birds from rearing fields. PMID- 26823317 TI - Movement of game birds from rearing fields. PMID- 26823318 TI - Veterinary involvement in poultry research. PMID- 26823319 TI - Reptile survey. PMID- 26823320 TI - Nutraceutical project. PMID- 26823324 TI - An expert generalist. PMID- 26823325 TI - Diary of a parliamentary intern. PMID- 26823326 TI - Hippocrates, Principles on Abdominal Surgery in Ancient Greece During the Fifth Century bc. PMID- 26823327 TI - A Novel Successive Suturing Device for Laparoscopic Surgery. AB - Suturing is one of the more tiresome and difficult tasks during laparoscopic surgeries. To cope with this problem, we aimed to develop a novel successive suturing device. A novel needle holding and locking mechanism is proposed to transfer the needle between the upper and bottom jaws. The device is straightforward to use with intuitive 2-trigger control, and it can perform successive suturing without the need of reload between stiches. Also, it is compact enough to be inserted through a 12-mm trocar. The feasibility of the device is verified through in vitro and in vivo experiments. It was found that the developed device was able to successfully close the wounds without any leakage. The developed successive suturing device offers an easy way of performing suture, and it will greatly help surgeons during laparoscopic surgeries. PMID- 26823328 TI - Toward 0% Bile Duct Injury During Laparoscopic Cholecystectomy? PMID- 26823329 TI - A Bis(Diphosphanyl N-Heterocyclic Carbene) Gold Complex: A Synthon for Luminescent Rigid AuAg2 Arrays and Au5 and Cu6 Double Arrays. AB - A mononuclear bis(NHC)/Au(I) (NHC=N-heterocyclic carbene) cationic complex with a rigid bis(phosphane)-functionalized NHC ligand (PC(NHC)P) was used to construct linear Au3 and Ag2 Au arrays, a Au5 cluster with two intersecting crosslike Au3 arrays, and an unprecedented Cu6 complex with two parallel Cu3 arrays. The impact of metallophilic interactions on photoluminescence was studied experimentally. PMID- 26823330 TI - Spinal arteriovenous fistulae in patients with hereditary hemorrhagic telangiectasia: A case report and systematic review of the literature. AB - BACKGROUND: Although rare, spinal arteriovenous malformations (AVMs) are thought to be more prevalent in the hereditary Hereditary Hemorrhagic Telangiectasia (HHT) population. METHODS: We report a case of a spinal AVM in a 37-year-old female with HHT treated with endovascular embolization. In addition, we report findings from a systematic review of the literature on the clinical characteristics, angioarchitecture, and clinical outcomes of HHT patients with spinal AVMs. RESULTS: The patient is a 37 year-old female with definite HHT who presented with a one-year history of progressive gait difficulty. The spinal fistula was incidentally detected on chest computed tomography (CT). Spinal angiography demonstrated a large perimedullary arteriovenous fistula was supplied by a posterolateral spinal artery. The fistula was treated with detachable coils. The patient made a complete neurological recovery. Our systematic review yielded 25 additional cases of spinal AVMs in HHT patients. All fistulae were perimedullary (100.0%). Treatments were described in 24 of the 26 lesions. Endovascular-only treatment was performed in 16 cases (66.6%) and surgical-only treatment was performed in five cases (20.8%). Complete or near-complete occlusion rates were 86.7% (13/15) for endovascular treated cases, 100.0% (4/4) for surgery and 66.6% (2/3) for combined treatments. Overall, 80.0% of patients (16/20) reported improvement in function following treatment, 100.0% (5/5) in the surgery group and 84.6% (11/13) reported improvement in the endovascular group. CONCLUSIONS: Spinal fistulae in HHT patients are usually type IV perimedullary fistulae. Both endovascular and surgical treatments appeared to be effective in treating these lesions. However, it is clear that endovascular therapy has become the preferred treatment modality. PMID- 26823331 TI - Wingspan stenting can effectively prevent long-term strokes for patients with severe symptomatic atherosclerotic basilar stenosis. AB - OBJECTIVE: To investigate the safety and long-term effect of using the Wingspan stent for severe symptomatic atherosclerotic basilar artery stenosis (>=70%). MATERIALS AND METHODS: Between July 2007 and April 2013, we had 91 consecutive patients (age range 41-82 years old) with symptomatic severe basilar stenosis (70 99%) who underwent Wingspan stenting at our center. All patients had stenosis related temporary ischemic attack or strokes. We analyzed the demographic data, pre- and post-procedural cerebral angiography, technical success rate, peri procedural complications, and clinical and imaging follow-ups. RESULTS: The Wingspan stenting procedure was successful in all patients: The stenosis was reduced from 82.2% +/- 5.8% pre-stenting to 15.9% +/- 5.7% post-stenting. The 30 day peri-operative rate for stroke or death was 14.3%, which included ischemic stroke in 12 cases (12/91 = 13.2%) and subarachnoid hemorrhage in one case (1/91 = 1.1%), with a fatal or disabling stroke rate of 2.2%. Among the 77 patients with clinical follow-up assessment within 7-60 months (mean 31.3 +/- 15.1 months) after stenting, four patients (5.2%) had posterior ischemia, including one patient with disabling ischemic stroke (1.3%) and three patients (3.9%) with temporary ischemic attack. The 2-year cumulative stroke rate was 16% (95% CI: 8.2 23.8%). Among 46 patients with imaging assessments at 3-45 months (mean, 9.5 +/- 8.3) post-stenting, six (13.0%) patients had restenosis, including two (2/46 = 4.3%) with symptomatic restenosis. CONCLUSIONS: The benefit of stenting for patients with severe basilar artery stenosis (> 70%) may lie in lowering the long term fatal and disabling stroke rate; and as long as the peri-operative stroke rate can be kept at a relatively lower level, patients with severe basilar stenosis can benefit from basilar artery stenting. PMID- 26823333 TI - BMP signaling in vascular biology and dysfunction. AB - The vascular system is critical for developmental growth, tissue homeostasis and repair but also for tumor development. Bone morphogenetic protein (BMP) signaling has recently emerged as a fundamental pathway of the endothelium by regulating cardiovascular and lymphatic development and by being causative for several vascular dysfunctions. Two vascular disorders have been directly linked to impaired BMP signaling: pulmonary arterial hypertension and hereditary hemorrhagic telangiectasia. Endothelial BMP signaling critically depends on the cellular context, which includes among others vascular heterogeneity, exposure to flow, and the intertwining with other signaling cascades (Notch, WNT, Hippo and hypoxia). The purpose of this review is to highlight the most recent findings illustrating the clear need for reconsidering the role of BMPs in vascular biology. PMID- 26823332 TI - Uricase alkaline enzymosomes with enhanced stabilities and anti-hyperuricemia effects induced by favorable microenvironmental changes. AB - Enzyme therapy is an effective strategy to treat diseases. Three strategies were pursued to provide the favorable microenvironments for uricase (UCU) to eventually improve its features: using the right type of buffer to constitute the liquid media where catalyze reactions take place; entrapping UCU inside the selectively permeable lipid vesicle membranes; and entrapping catalase together with UCU inside the membranes. The nanosized alkaline enzymosomes containing UCU/(UCU and catalase) (ESU/ESUC) in bicine buffer had better thermal, hypothermal, acid-base and proteolytic stabilities, in vitro and in vivo kinetic characteristics, and uric acid lowering effects. The favorable microenvironments were conducive to the establishment of the enzymosomes with superior properties. It was the first time that two therapeutic enzymes were simultaneously entrapped into one enzymosome having the right type of buffer to achieve added treatment efficacy. The development of ESU/ESUC in bicine buffer provides valuable tactics in hypouricemic therapy and enzymosomal application. PMID- 26823334 TI - Implementation of a Systematic Accountability Framework in 2014 to Improve the Performance of the Nigerian Polio Program. AB - BACKGROUND: An accountability framework is a central feature of managing human and financial resources. One of its primary goals is to improve program performance through close monitoring of selected priority activities. The principal objective of this study was to determine the contribution of a systematic accountability framework to improving the performance of the World Health Organization (WHO)-Nigeria polio program staff, as well as the program itself. METHODS: The effect of implementation of the accountability framework was evaluated using data on administrative actions and select process indicators associated with acute flaccid paralysis (AFP) surveillance, routine immunization, and polio supplemental immunization activities. Data were collected in 2014 during supportive supervision, using Magpi software (a company that provides service to collect data using mobile phones). A total of 2500 staff were studied. RESULTS: Data on administrative actions and process indicators from quarters 2-4 in 2014 were compared. With respect to administrative actions, 1631 personnel (74%) received positive feedback (written or verbal commendation) in quarter 4 through the accountability framework, compared with 1569 (73%) and 1152 (61%) during quarters 3 and 2, respectively. These findings accorded with data on process indicators associated with AFP surveillance and routine immunization, showing statistically significant improvements in staff performance at the end of quarter 4, compared with other quarters. CONCLUSIONS: Improvements in staff performance and process indicators were observed for the WHO-Nigeria polio program after implementation of a systematic accountability framework. PMID- 26823335 TI - A Randomized, Controlled Trial of the Impact of Alternative Dosing Schedules on the Immune Response to Human Rotavirus Vaccine in Rural Ghanaian Infants. AB - BACKGROUND: The recommended schedule for receipt of 2-dose human rotavirus vaccine (HRV) coincides with receipt of the first and second doses of diphtheria, pertussis, and tetanus vaccine (ie, 6 and 10 weeks of age, respectively). Alternative schedules and additional doses of HRV have been proposed and may improve vaccine performance in low-income countries. METHODS: In this randomized trial in rural Ghana, HRV was administered at ages 6 and 10 weeks (group 1), 10 and 14 weeks (group 2), or 6, 10, and 14 weeks (group 3). We compared serum antirotavirus immunoglobulin A (IgA) seroconversion (>=20 U/mL) and geometric mean concentrations (GMCs) between group 1 and groups 2 and 3. RESULTS: Ninety three percent of participants (424 of 456) completed the study per protocol. In groups 1, 2, and 3, the IgA seroconversion frequencies among participants with IgA levels of <20 U/mL at baseline were 28.9%, 37.4%, and 43.4%, respectively (group 1 vs group 3, P = .014; group 1 vs group 2, P = .163). Postvaccination IgA GMCs were 22.1 U/mL, 26.5 U/mL, and 32.6 U/mL in groups 1, 2, and 3, respectively (group 1 vs group 3, P = .038; group 1 vs group 2, P = .304). CONCLUSIONS: A third dose of HRV resulted in increased seroconversion frequencies and GMCs, compared with 2 doses administered at 6 and 10 weeks of age. Since there is no correlate of protection, a postmarketing effectiveness study is required to determine whether the improvement in immune response translates into a public health benefit in low-income countries. CLINICAL TRIALS REGISTRATION: NCT015751. PMID- 26823336 TI - Can Changes to Scheduling Enhance the Performance of Rotavirus Vaccines in Low Income Countries? PMID- 26823337 TI - Vaccine-Induced Immunogenicity and Protection Against Pneumocystis Pneumonia in a Nonhuman Primate Model of HIV and Pneumocystis Coinfection. AB - BACKGROUND: The ubiquitous opportunistic pathogen Pneumocystis jirovecii causes pneumonia in immunocompromised individuals, including human immunodeficiency virus (HIV)-infected individuals, and pulmonary colonization with P. jirovecii is believed to be a cofactor in the development of chronic obstructive pulmonary disease. There is no vaccine for P. jirovecii; however, most adults are seropositive, indicating natural immune priming to this pathogen. We have shown that humoral response to a recombinant subunit of the P. jirovecii protease kexin (KEX1) correlates with protection from P. jirovecii colonization and pneumonia. METHODS: Here we evaluated the immunogenicity and protective capacity of the recombinant KEX1 peptide vaccine in a preclinical, nonhuman primate model of HIV induced immunosuppression and Pneumocystis coinfection. RESULTS: Immunization with KEX1 induced a robust humoral response remained at protective levels despite chronic simian immunodeficiency virus/HIV-induced immunosuppression. KEX1 immunized macaques were protected from Pneumocystis pneumonia, compared with mock immunized animals (P= .047), following immunosuppression and subsequent natural, airborne exposure to Pneumocystis CONCLUSIONS: These data support the concept that stimulation of preexisting immunological memory to Pneumocystis with a recombinant KEX1 vaccine prior to immunosuppression induces durable memory responses and protection in the context of chronic, complex immunosuppression. PMID- 26823338 TI - Noninterference of Rotavirus Vaccine With Measles-Rubella Vaccine at 9 Months of Age and Improvements in Antirotavirus Immunity: A Randomized Trial. AB - BACKGROUND: The burden of rotavirus morbidity and mortality is high in children aged <5 years in developing countries, and evaluations indicate waning protection from rotavirus immunization in the second year. An additional dose of rotavirus vaccine may enhance the immune response and lengthen the period of protection against disease, but coadministration of this dose should not interfere with immune responses to concurrently given vaccines. METHODS: A total of 480 9-month old participants from Matlab, Bangladesh, were enrolled in a study with a primary objective to establish noninferiority of concomitant administration of measles rubella vaccine (MR) and a third dose of human rotavirus vaccine (HRV; MR + HRV), compared with MR given alone. Secondary objectives included noninferiority of rubella antibody seroconversion and evaluating rotavirus IgA/IgG seroresponses in MR + HRV recipients. RESULTS: Two months after vaccination, 75.3% and 74.3% of MR + HRV and MR recipients, respectively, had seroprotective levels of measles virus antibodies; 100.0% and 99.6%, respectively, showed anti-rubella virus immunoglobulin G (IgG) seroprotection. In the MR + HRV group, antirotavirus immunoglobulin A and IgG seropositivity frequencies before vaccination (52.7% and 66.3%, respectively) increased to 69.6% and 88.3% after vaccination. CONCLUSIONS: Vaccine-induced measles and rubella antibody responses are not negatively affected by concomitant administration of HRV. The HRV dose increases antirotavirus serum antibody titers and the proportion of infants with detectable antirotavirus antibody. CLINICAL TRIALS REGISTRATION: NCT01700621. PMID- 26823339 TI - Intercostal muscle motor behavior during tracheal occlusion conditioning in conscious rats. AB - A respiratory load compensation response is characterized by increases in activation of primary respiratory muscles and/or recruitment of accessory respiratory muscles. The contribution of the external intercostal (EI) muscles, which are a primary respiratory muscle group, during normal and loaded breathing remains poorly understood in conscious animals. Consciousness has a significant role on modulation of respiratory activity, as it is required for the integration of behavioral respiratory responses and voluntary control of breathing. Studies of respiratory load compensation have been predominantly focused in anesthetized animals, which make their comparison to conscious load compensation responses challenging. Using our established model of intrinsic transient tracheal occlusions (ITTO), our aim was to evaluate the motor behavior of EI muscles during normal and loaded breathing in conscious rats. We hypothesized that 1) conscious rats exposed to ITTO will recruit the EI muscles with an increased electromyogram (EMG) activation and 2) repeated ITTO for 10 days would potentiate the baseline EMG activity of this muscle in conscious rats. Our results demonstrate that conscious rats exposed to ITTO respond by recruiting the EI muscle with a significantly increased EMG activation. This response to occlusion remained consistent over the 10-day experimental period with little or no effect of repeated ITTO exposure on the baseline ?EI EMG amplitude activity. The pattern of activation of the EI muscle in response to an ITTO is discussed in detail. The results from the present study demonstrate the importance of EI muscles during unloaded breathing and respiratory load compensation in conscious rats. PMID- 26823340 TI - Relationship of brown adipose tissue perfusion and function: a study through beta2-adrenoreceptor stimulation. AB - Brown adipose tissue (BAT) activation increases glucose and lipid consumption; as such, it is been considered as a potential therapy to decrease obesity. BAT is highly vascularized and its activation is associated with a necessary increase in blood flow. However, whether increasing BAT blood flow per se increases BAT activity is unknown. To examine this hypothesis, we investigated whether an isolated increase in BAT blood flow obtained by beta2-adrenoreceptor (beta2-AR) stimulation with salbutamol increased BAT activity. BAT blood flow was estimated in vivo in mice using contrast-enhanced ultrasound. The absence of direct effect of salbutamol on the function of isolated brown adipocytes was assessed by measuring oxygen consumption. The effect of salbutamol on BAT activity was investigated by measuring BAT glucose uptake in vivo. BAT blood flow increased by 2.3 +/- 0.6-fold during beta2-AR stimulation using salbutamol infusion in mice (P= 0.003). beta2-AR gene expression was detectable in BAT but was extremely low in isolated brown adipocytes. Oxygen consumption of isolated brown adipocytes did not change with salbutamol exposure, confirming the absence of a direct effect of beta2-AR agonist on brown adipocytes. Finally, beta2-AR stimulation by salbutamol increased BAT glucose uptake in vivo (991 +/- 358 vs. 135 +/- 49 ng glucose/mg tissue/45 min in salbutamol vs. saline injected mice, respectively,P= 0.046). In conclusion, an increase in BAT blood flow without direct stimulation of the brown adipocytes is associated with increased BAT metabolic activity. Increasing BAT blood flow might represent a new therapeutic target in obesity. PMID- 26823341 TI - Effect of exercise training and myocardial infarction on force development and contractile kinetics in isolated canine myocardium. AB - It is well known that moderate exercise training elicits a small increase in ventricular mass (i.e., a physiological hypertrophy) that has many beneficial effects on overall cardiac health. It is also well known that, when a myocardial infarction damages part of the heart, the remaining myocardium remodels to compensate for the loss of viable functioning myocardium. The effects of exercise training, myocardial infarction (MI), and their interaction on the contractile performance of the myocardium itself remain largely to be determined. The present study investigated the contractile properties and kinetics of right ventricular myocardium isolated from sedentary and exercise trained (10-12 wk progressively increasing treadmill running, begun 4 wk after MI induction) dogs with and without a left ventricular myocardial infarction. Exercise training increased force development, whereas MI decreased force development that was not improved by exercise training. Contractile kinetics were significantly slower in the trained dogs, whereas this impact of training was less or no longer present after MI. Length-dependent activation, both evaluated on contractile force and kinetics, was similar in all four groups. The control exercise-trained group exhibited a more positive force-frequency relationship compared with the sedentary control group while both sedentary and trained post-MI dogs had a more negative relationship. Last, the impact of the beta-adrenergic receptor agonist isoproterenol resulted in a similar increase in force and acceleration of contractile kinetics in all groups. Thus, exercise training increased developed force but slowed contractile kinetics in control (noninfarcted animals), actions that were attenuated or completely absent in post-MI dogs. PMID- 26823342 TI - Vibrotactile stimulation of fast-adapting cutaneous afferents from the foot modulates proprioception at the ankle joint. AB - It has previously been shown that cutaneous sensory input from across a broad region of skin can influence proprioception at joints of the hand. The present experiment tested whether cutaneous input from different skin regions across the foot can influence proprioception at the ankle joint. The ability to passively match ankle joint position (17 degrees and 7 degrees plantar flexion and 7 degrees dorsiflexion) was measured while cutaneous vibration was applied to the sole (heel, distal metatarsals) or dorsum of the target foot. Vibration was applied at two different frequencies to preferentially activate Meissner's corpuscles (45 Hz, 80 MUm) or Pacinian corpuscles (255 Hz, 10 MUm) at amplitudes ~3 dB above mean perceptual thresholds. Results indicated that cutaneous input from all skin regions across the foot could influence joint-matching error and variability, although the strongest effects were observed with heel vibration. Furthermore, the influence of cutaneous input from each region was modulated by joint angle; in general, vibration had a limited effect on matching in dorsiflexion compared with matching in plantar flexion. Unlike previous results in the upper limb, we found no evidence that Pacinian input exerted a stronger influence on proprioception compared with Meissner input. Findings from this study suggest that fast-adapting cutaneous input from the foot modulates proprioception at the ankle joint in a passive joint-matching task. These results indicate that there is interplay between tactile and proprioceptive signals originating from the foot and ankle. PMID- 26823343 TI - Greater loss in muscle mass and function but smaller metabolic alterations in older compared with younger men following 2 wk of bed rest and recovery. AB - This investigation aimed to compare the response of young and older adult men to bed rest (BR) and subsequent rehabilitation (R). Sixteen older (OM, age 55-65 yr) and seven young (YM, age 18-30 yr) men were exposed to a 14-day period of BR followed by 14 days of R. Quadriceps muscle volume (QVOL), force (QF), and explosive power (QP) of leg extensors; single-fiber isometric force (Fo); peak aerobic power (Vo2peak); gait stride length; and three metabolic parameters, Matsuda index of insulin sensitivity, postprandial lipid curve, and homocysteine plasma level, were measured before and after BR and after R. Following BR, QVOL was smaller in OM (-8.3%) than in YM (-5.7%,P= 0.031); QF (-13.2%,P= 0.001), QP ( 12.3%,P= 0.001), and gait stride length (-9.9%,P= 0.002) were smaller only in OM. Fo was significantly smaller in both YM (-32.0%) and OM (-16.4%) without significant differences between groups. Vo2peakdecreased more in OM (-15.3%) than in YM (-7.6%,P< 0.001). Instead, the Matsuda index fell to a greater extent in YM than in OM (-46.0% vs. -19.8%, respectively,P= 0.003), whereas increases in postprandial lipid curve (+47.2%,P= 0.013) and homocysteine concentration (+26.3%,P= 0.027) were observed only in YM. Importantly, after R, the recovery of several parameters, among them QVOL, QP, and Vo2peak, was not complete in OM, whereas Fo did not recover in either age group. The results show that the effect of inactivity on muscle mass and function is greater in OM, whereas metabolic alterations are greater in YM. Furthermore, these findings show that the recovery of preinactivity conditions is slower in OM. PMID- 26823345 TI - Preparation and Characteristics of a Novel Sorptive Extraction Stir Bar Based on Cd-Imprinted Polymer Monoliths. AB - A novel monolithic stir-bar for Cd(II) sorption extraction was prepared by ion imprinting technology and in situ stepwise polymerization of epoxy resin (EP). The condensation product of diethylenetriamine and thiourea (DETATUC) was used as a curing agent, with Cd ions as template ions and polyethylene glycol 1540 as a porogenic agent. The main parameters of the stir-bar sorption extraction-EP DETATUC material for the extraction and desorption of Cd(II) in aqueous solution were investigated, and inductively coupled plasma-atomic emission spectrometry was performed. The results showed that the monolithic material possessed good permeability and reusability. The maximum adsorption capacity was 136.58 MUmol g( 1) at pH 6.0. The optimized conditions were the following: stirring rate at 300 rpm, adsorption time at 40 min, elution media at 0.25 mol L(-1) EDTA, and elution time at 20 min. The accuracy of the method was assessed by spiking two water samples and one plant sewage sample with Cd at two concentration levels. Recoveries of 96-102% were obtained. PMID- 26823344 TI - Temperature and blood flow distribution in the human leg during passive heat stress. AB - The influence of temperature on the hemodynamic adjustments to direct passive heat stress within the leg's major arterial and venous vessels and compartments remains unclear. Fifteen healthy young males were tested during exposure to either passive whole body heat stress to levels approaching thermal tolerance [core temperature (Tc) + 2 degrees C; study 1; n = 8] or single leg heat stress (Tc + 0 degrees C; study 2; n = 7). Whole body heat stress increased perfusion and decreased oscillatory shear index in relation to the rise in leg temperature (Tleg) in all three major arteries supplying the leg, plateauing in the common and superficial femoral arteries before reaching severe heat stress levels. Isolated leg heat stress increased arterial blood flows and shear patterns to a level similar to that obtained during moderate core hyperthermia (Tc + 1 degrees C). Despite modest increases in great saphenous venous (GSV) blood flow (0.2 l/min), the deep venous system accounted for the majority of returning flow (common femoral vein 0.7 l/min) during intense to severe levels of heat stress. Rapid cooling of a single leg during severe whole body heat stress resulted in an equivalent blood flow reduction in the major artery supplying the thigh deep tissues only, suggesting central temperature-sensitive mechanisms contribute to skin blood flow alone. These findings further our knowledge of leg hemodynamic responses during direct heat stress and provide evidence of potentially beneficial vascular alterations during isolated limb heat stress that are equivalent to those experienced during exposure to moderate levels of whole body hyperthermia. PMID- 26823346 TI - Left atrial impression by a dilated oesophagus in a patient with limited cutaneous systemic sclerosis. PMID- 26823347 TI - Hypercholesterolaemic valvulopathy in a young woman with heterozygous familial hypercholesterolaemia. PMID- 26823348 TI - Black bone disease in a healing fracture. AB - Black bone disease refers to the hyperpigmentation of bone secondary to prolonged usage of minocycline. We present a report of a 34-year-old man who underwent femoral shaft fracture fixation complicated by deep infection requiring debridement. The implants were removed 10 months later after long-term treatment with minocycline and fracture union. A refracture of the femoral shaft occurred 2 days after implant removal and repeat fixation was required. Intraoperatively, abundant heavily pigmented and dark brown bone callus was noted over the old fracture site. There was no evidence of other bony pathology and the appearance was consistent with minocycline-associated pigmentation. As far as we are aware, this is the first case of black bone disease affecting callus within the interval period of bone healing. We also discuss the relevant literature on black bone disease to bring light on this rare entity that is an unwelcomed surprise to operating orthopaedic surgeons. PMID- 26823349 TI - Severe vitamin C deficiency in a child newly diagnosed with T-cell ALL due to nutrient gap. AB - A 10-year-old boy developed a perifollicular rash during interim maintenance of T Cell acute lymphoblastic leukaemia. Differential diagnoses included drug reaction and inflammatory process. Before diagnosis, the patient had a limited diet--low in vegetables and fruits--due to selective eating, with later anorexia and taste aversions due to chemotherapy treatment. Despite nutritional counselling and starting a multivitamin, the patient incurred severe weight loss (18.5% of his usual body weight). Serum levels of ascorbic acid were non-detectable, at <5 MUmol/L, indicative of vitamin C deficiency. The patient began vitamin C supplementation containing 125 mg ascorbic acid three times a day for 7 days, then 125 mg once daily for 3 months to normalise serum vitamin C. After ascorbic acid treatment was completed, the patient started a complete multivitamin and made efforts to eat fruits and vegetables rich in vitamin C. His serum ascorbic acid concentrations normalised to 52 MUmol/L 3 months after receiving supplementation. PMID- 26823350 TI - Unilateral absence of the pulmonary artery and cavernous transformation of portal vein: a rare combination. PMID- 26823351 TI - Osteomalacia with low alkaline phosphatase: a not so rare condition with important consequences. AB - Hypophosphatasia is a genetic disorder, characterised by a dysfunctional tissue non-specific isoenzyme of alkaline phosphatase that impacts bone metabolism and predisposes to osteomalacia or rickets. The clinical presentation is very diverse, depending on the age of onset and the severity of the disease. Several forms of hypophosphatasia are recognised. We present a case of a 50-year-old woman with low impact fractures and loss of teeth at a young age. She also had a low alkaline phosphatase and was diagnosed with adult hypophosphatasia. Although the severe forms of hypophosphatasia are rather rare, the adult form is thought to occur quite frequently. As this condition is not well known by healthcare professionals, the time to diagnosis and initiation of adequate treatment is often postponed. When encountering a patient with low alkaline phosphatase, low bone density or a history of bone fractures, the possibility of hypophosphatasia should be considered. PMID- 26823352 TI - Crossed fused renal ectopia with chyluria: a rare presentation. PMID- 26823353 TI - Disappearing large calcified thoracic disc herniation in a patient with thalassaemia. AB - Regression of herniated disc fragments with subsequent improvement in clinical symptoms has been reported in the lumbar and cervical spine. Such regressions in the thoracic spine are extremely rare. We report a case of a 38-year-old patient with thalassaemia who had regression of a large calcified herniated thoracic disc causing cord compression, with subsequent herniation of a second calcified disc at a different level and discuss the possible aetiopathogenesis. This is the first such case reported in the thalassaemia population. PMID- 26823354 TI - Hepatic abscess-associated Clostridial bacteraemia presenting with intravascular haemolysis and severe hypertension. AB - Clostridium perfringens bacteraemia is a potentially fatal condition, and its early identification is paramount to maximise chances of survival. Prompt recognition of intravascular haemolysis, a known complication of C. perfringens bacteraemia, can help guide clinical decision-making before microbiology data becomes available. We present a novel finding of severe hypertension in a fatal case of Clostridial bacteraemia with massive haemolysis. A 58-year-old man with no known medical history presented to the emergency department with malaise, fever and hypertension. He developed abdominal pain and a hepatic abscess was identified on CT imaging. Within 4 h of presentation, he developed massive intravascular haemolysis, extreme hypertension, pulmonary oedema and respiratory failure. He died less than 8 h after presentation. His blood cultures subsequently grew C. perfringens. This case underscores the importance of early recognition of intravascular haemolysis complicating C. perfringens bacteraemia, and discusses the rare complication of hypertensive emergency in this setting. PMID- 26823355 TI - High-velocity facial gunshot wounds: multidisciplinary care from prehospital to discharge. AB - A case is presented in which a high velocity rifle (shotgun) was fired into the inferior part of a patient's face in an attempted suicide causing widespread trauma to the inferior and left side of the patient's face. He presented to his general practitioner where an ambulance was called. The patient is followed from prehospital care (air ambulance) to resuscitation in accident and emergency and through the first stages of reconstructive surgery. The article focuses on the multidisciplinary approach to the patient's prehospital care and initial resuscitation at a major trauma centre. CT reconstruction images of the patient's skull allow visualisation of the extent of bone damage at presentation. Medical photography allows visualisation of the extent of the initial damage and shows how reconstructive surgery was undertaken early and in progressive stages. A literature review was performed allowing discussion of the current evidence and best practice in the management of facial gunshot wounds. PMID- 26823356 TI - Use of butane-isobutane refrigerant spray in the management of a mucocoele in a visually impaired child. AB - Mucocoeles are commonly observed lesions in children and young adults. Conventional management using a scalpel aims at enucleation, requiring psychological preparation of the parent as well as the child because of inherent fear and apprehension towards surgery. This is still more complex in children with visual impairment. The other management techniques are laser, cryotherapy and micromarsupialisation, management strategies that, being painless and tolerable, reduce the anxiety of the child and are therefore more acceptable. The basic technique of cryotherapy stresses on rapid cooling, gradual thawing and repeated freezing to ensure tissue destruction. We report a case of a 13-year-old boy with visual impairment, presenting with a mucocoele on the lower lip, which was managed using butane-isobutane refrigerant spray, which is otherwise routinely employed for pulp vitality testing. A single, 2 min freeze/thaw cycle was used. The healing was uneventful. PMID- 26823357 TI - Rare encounter of unilateral facial nerve palsy in an adolescent with Guillain Barre syndrome. AB - Unilateral facial nerve palsy is rarely encountered in Guillain-Barre syndrome (GBS). We report a case of an adolescent girl who presented with peripheral ascending weakness, preceded by Campylobacter jejuni infection. After treatment with intravenous immunoglobulin, the peripheral weakness improved. Electro diagnostic testing confirmed axonal dysfunction and the patient was positive for antiganglioside antibodies. However, the patient developed unilateral left-sided facial weakness. She was managed with further intravenous immunoglobulin and intensive physiotherapy. The outcome for facial palsy was very good, with almost complete resolution after 2 weeks. PMID- 26823358 TI - Advanced rectal cancer in a long-term Hartmann's pouch: a forgotten organ revisited. AB - Hartmann's procedure is widely performed as a first-stage operation in cases of left colon emergencies when a one stage management is judged to be unsafe. Forty per cent of patients with Hartmann's procedure never get their stoma reversed, ending with a permanent stoma. The distal excluded Hartmann's pouch is usually forgotten compared to the proximal functioning colon. A 70-year-old man with Hartmann's procedure carried out previously for complicated diverticular disease presented with bleeding per rectum. Invasive adenocarcinoma was confirmed on histology. Subsequent staging revealed a locally advanced rectal cancer. The tumour progressed despite a course of neoadjuvant chemoradiation. The general condition of the patient deteriorated with development of renal failure. The patient died a few weeks later. By reporting this case, we are revisiting the long forgotten Hartmann's pouch to highlight the potential pathologies in the distal stump and to emphasise that a distal stump should not be forgotten even in asymptomatic patients. PMID- 26823359 TI - Sodium valproate-induced Fanconi type proximal renal tubular acidosis. AB - We present a case series of three patients with sodium valproate-induced Fanconi's syndrome, with ages ranging from 5 years to 12 years. The most important diagnostic features of this syndrome include hypophosphataemia, glycosuria and proteinuria, which are also noted in our series. Furthermore, also added is that clinical fractures representing an underlying osteopaenia may provide an opportunity for early intervention as it raises the suspicion of Fanconi's syndrome. Previous case reports suggest there is a subpopulation of individuals who are at risk of developing this condition. These individuals share similar characteristics, including being non-ambulatory, developmentally delayed and/or tube fed. Withdrawing sodium valproate therapy is the ultimate treatment for valproate-induced Fanconi's syndrome and from previous case series, normalised renal function occurs in approximately 6 months. Often, supplement support is also required for deranged electrolyte balance. PMID- 26823360 TI - Spontaneous spinal subarachnoid haemorrhage: a not so benign disease with devastating results. PMID- 26823361 TI - A novel haemoglobin variant mimicking cyanotic congenital heart disease. AB - Screening for critical congenital heart defects in newborn babies can aid in early recognition, with the prospect of improved outcome. However, as this universal newborn screening is implemented, there will be an increasing number of false-positive results. In order to avoid multiple investigations and uncertainty, an haemoglobin (Hb) variant must be included in the differential diagnosis in otherwise well newborns with low oxygen saturation by pulse oximetry. We describe a novel fetal Hb variant (heterozygous gamma-globin gene (HBG1) mutation in exon 2 c.202G>A (p.Val68Met)) identified in a newborn with positive pulse oximetry screening for congenital heart disease. PMID- 26823362 TI - Pilonidal sinus of the chin: mistreated as a dental fistula. AB - Pilonidal sinus is a chronic inflammatory condition associated with penetration of hair particles into the skin. It is rare in the chin area and, to our knowledge, there is only one such reported case. A 56-year-old man was previously admitted to a private clinic, with a hard mass on his anterior buccal sulcus. Three of the patient's teeth were extracted as the swelling was thought to be associated with a dental infection. Because the fistula did not resolve, the patient was referred to our department. Following radiological and clinical examinations, the hard mass was reached intraorally and hair shafts were seen inside it. The area was closed primarily after cleaning the inflammatory tissues and the hairs. The recovery period was uneventful. In this case report, we present a pilonidal sinus encountered in the chin area, the wrong treatment initially given to the patient and the subsequent treatment carried out by us. PMID- 26823363 TI - Multiple sclerosis in a postgraduate student of anaesthesia: illness in doctors and fitness to practice. AB - A 29-year-old previously healthy woman, a doctor, was diagnosed with remitting relapsing multiple sclerosis after fulfilling McDonald's criteria for the diagnosis of definite multiple sclerosis. Despite 22 months of immunomodulatory treatment, the feasibility of continuing to train in a stressful specialty of medicine became an ethical and practical dilemma. Fitness for practice and career advancement among doctors with illnesses or having cognitive and physical decline from disease and/or ageing is a global problem. The need for addressing this issue in a compassionate and comprehensive manner is discussed. Cognitive and physical fitness are required in doctors and other healthcare workers since medical errors/adverse events are commonplace in medical practice. The public welfare is equally important in this global problem. PMID- 26823364 TI - 'Epinephrine-resistant' angioedema. AB - A man in his 60s was brought to the emergency department, with airway compromise and dysarthria due to a grossly enlarged tongue. As he was on a current course of antibiotics, he was treated for a likely antibiotic-associated allergic reaction. However, as he failed to improve with intramuscular and nebulised epinephrine, another cause of his symptoms was sought. Further discussion revealed a history of chronic lymphocytic leukaemia (CLL), which had recently relapsed. Investigations were ordered to confirm that the symptoms were due to acquired angioedema, and the patient was managed for this diagnosis based on the presence of an undetectable C4 level. This diagnosis was later confirmed when the results of specialist tests became available. The patient was treated for his relapsed CLL with good effect, and has had no further episodes of angioedema and an improvement in the level of his C1 esterase protein level and function. PMID- 26823366 TI - Intraoperative analysis of cross-talk inhibition between diaphragmatic and cardiac pacemakers. PMID- 26823365 TI - Colonic metastasis in mucoepidermoid carcinoma of the parotid: a rare occurrence. AB - We present a case of intermediate-grade mucoepidermoid carcinoma of the parotid with late local recurrence and colonic metastasis. A 69-year-old man who had undergone right total conservative parotidectomy followed by adjuvant radiotherapy for intermediate-grade mucoepidermoid carcinoma 10 years prior, presented with a recurrent swelling in the postoperative site and cardiac failure. On evaluation, he was found to have severe anaemia with positive stool occult blood. Colonoscopic evaluation revealed a globular submucosal bulge with erosion 40 cm from the anal verge, the biopsy of which was consistent with mucoepidermoid carcinoma. The presentation, diagnostic details and management of this rare case are discussed. PMID- 26823367 TI - Severe case of asbestos-related lung diseases. PMID- 26823368 TI - A Bayesian Belief Network for Murray Valley encephalitis virus risk assessment in Western Australia. AB - BACKGROUND: Murray Valley encephalitis virus (MVEV) is a clinically important virus in Australia responsible for a number of epidemics over the past century. Since there is no vaccine for MVEV, other preventive health measures to curtail its spread must be considered, including the development of predictive risk models and maps to help direct public health interventions. This article aims to support these approaches by presenting a model for assessing MVEV risk in Western Australia (WA). METHODS: A Bayesian Belief Network (BBN) for assessing MVEV risk was developed and used to quantify and map disease risks in WA. The model combined various abiotic, biotic, and anthropogenic factors that might affect the risk of MVEV into a predictive framework, based on the ecology of the major mosquito vector and waterbird hosts of MVEV. It was further refined and tested using retrospective climate data from 4 years (2000, 2003, 2009, and 2011). RESULTS: Implementing the model across WA demonstrated that it could predict locations of human MVEV infection and sentinel animal seroconversion in the 4 years tested with some degree of accuracy. In general, risks are highest in the State's north and lower in the south. The model predicted that short-term climate change, based on the Intergovernmental Panel on Climate Change's A1B emissions scenario, would decrease MVEV risks in summer and autumn, largely due to higher temperatures decreasing vector survival. CONCLUSIONS: To our knowledge, this is the first model to use a BBN to quantify MVEV risks in WA. The models and maps developed here may assist public health agencies in preparing for and managing Murray Valley encephalitis in the future. In its current form, the model is knowledge-driven and based on the analysis of potential risk factors that affect the dynamics of MVEV using retrospective data. Further work and additional testing should be carried out to test its validity in future years. PMID- 26823370 TI - Ocular involvement in an HIV-infected patient: not always an infectious disease. An interesting case without apparent cause. AB - We describe the case of a young girl with vertically-transmitted HIV infection who presented with chronic ocular inflammation characterized by several relapses and remissions. Good viral and immunological status made infective or neoplastic causes unlikely; the diagnosis was challenging and finally spontaneous remission was observed after several months. Clinical and histopathological findings made idiopathic orbital inflammatory syndrome the most probable diagnosis for our patient. PMID- 26823369 TI - Non-invasive imaging of oxygen extraction fraction in adults with sickle cell anaemia. AB - Sickle cell anaemia is a monogenetic disorder with a high incidence of stroke. While stroke screening procedures exist for children with sickle cell anaemia, no accepted screening procedures exist for assessing stroke risk in adults. The purpose of this study is to use novel magnetic resonance imaging methods to evaluate physiological relationships between oxygen extraction fraction, cerebral blood flow, and clinical markers of cerebrovascular impairment in adults with sickle cell anaemia. The specific goal is to determine to what extent elevated oxygen extraction fraction may be uniquely present in patients with higher levels of clinical impairment and therefore may represent a candidate biomarker of stroke risk. Neurological evaluation, structural imaging, and the non-invasive T2 relaxation-under-spin-tagging magnetic resonance imaging method were applied in sickle cell anaemia (n = 34) and healthy race-matched control (n = 11) volunteers without sickle cell trait to assess whole-brain oxygen extraction fraction, cerebral blood flow, degree of vasculopathy, severity of anaemia, and presence of prior infarct; findings were interpreted in the context of physiological models. Cerebral blood flow and oxygen extraction fraction were elevated (P < 0.05) in participants with sickle cell anaemia (n = 27) not receiving monthly blood transfusions (interquartile range cerebral blood flow = 46.2-56.8 ml/100 g/min; oxygen extraction fraction = 0.39-0.50) relative to controls (interquartile range cerebral blood flow = 40.8-46.3 ml/100 g/min; oxygen extraction fraction = 0.33 0.38). Oxygen extraction fraction (P < 0.0001) but not cerebral blood flow was increased in participants with higher levels of clinical impairment. These data provide support for T2-relaxation-under-spin-tagging being able to quickly and non-invasively detect elevated oxygen extraction fraction in individuals with sickle cell anaemia with higher levels of clinical impairment. Our results support the premise that magnetic resonance imaging-based assessment of elevated oxygen extraction fraction might be a viable screening tool for evaluating stroke risk in adults with sickle cell anaemia. PMID- 26823371 TI - Association between posterior crossbite, skeletal, and muscle asymmetry: a systematic review. AB - BACKGROUND: Of the various malocclusions, unilateral posterior crossbite has often been associated to skeletal and muscular asymmetrical growth and function. OBJECTIVE: To assess, by systematically reviewing the literature, the association between unilateral posterior crossbite (UPCB) and morphological and/or functional asymmetries (i.e. skeletal, masticatory muscle electromyographic (EMG) performance, bite force, muscle thickness, and chewing cycle asymmetries). MATERIALS AND METHODS: A literature survey covering the period from January 1965 to June 2015 was performed. Two reviewers extracted the data independently and assessed the quality of the studies. RESULTS: The search strategy resulted in 2184 citations, of which 45 met the inclusion criteria. The scientific and methodological quality of these studies was medium-low, irrespective of the association reported. In several studies, posterior crossbite is reported to be associated to asymmetries in mandibular skeletal growth, EMG activity, and the chewing cycle. Fewer data are available on bite force and masticatory muscle thickness. CONCLUSIONS: The relationship between unilateral posterior crossbite and skeletal asymmetry is still unresolved. To date, most of the studies available report a skeletal asymmetric growth. EMG activity of masticatory muscles is different between crossbite and non-crossbite sides. Subjects with UPCB show smaller bite force than non-crossbite subjects. There is no consistency of studies reporting masticatory muscle thickness asymmetry in UPCB subjects. UPCB is associated to an increase in the reverse chewing cycle. The literature available on the subject is of medium-low scientific and methodological quality, irrespective of the association reported. Further investigations with higher sample size, well-defined diagnostic criteria, rigorous scientific methodologies, and long-term control are needed. PMID- 26823372 TI - Radiographic technique and brackets affect measurements of proximal enamel thickness on mandibular incisors. AB - OBJECTIVE: To investigate the influence of radiographic film and tube positioning, the presence and the size of brackets on in vitro measurements of proximal enamel thickness of mandibular incisors on periapical radiographs aimed to aid planning of interproximal enamel reduction procedures in orthodontics. MATERIALS AND METHODS: Eighty human mandibular incisors were assigned to sets of four and located in a customized base. Periapical radiographs were taken with the film positioned at three different angles (0 degrees , 2 degrees , and 5 degrees ) in relation to the frontal plane and the tube head positioned at five angles (0 degrees , -2 degrees , -5 degrees , +2 degrees , and +5 degrees ) in relation to the sagittal plane. The proximal enamel width was calculated by means of computerized image analysis and compared with measurements obtained at 0 degrees . Statistical analysis was carried out to compare the enamel measurements on radiographs made with all angular combinations with and without the presence of brackets of different dimensions. RESULTS: A significant difference (P < 0.05) was found between the measurements of proximal enamel width obtained at the different angles in relation to the frontal and sagittal planes for all sets with or without brackets. The presence of brackets significantly affected the measured width only for the enamel side further away from the radiation source at the sagittal plane (P < 0.05). CONCLUSION: Angular changes in taking periapical radiographs of mandibular incisors and the presence of brackets significantly affect interproximal enamel measurements made with image analysis software. PMID- 26823373 TI - Bifidobacterium eulemuris sp. nov., isolated from faeces of black lemurs (Eulemur macaco). AB - Forty-three strains of bifidobacteria were isolated from the faeces of two adult black lemurs, Eulemur macaco. Thirty-four were identified as Bifidobacterium lemurum, recently described in Lemur catta. The nine remaining isolates were Gram positive-staining, non-spore-forming, fructose-6-phosphate phosphoketolase positive, microaerophilic, irregular rod-shaped bacteria that often presented Y- or V-shaped cells. Typing techniques revealed that these isolates were nearly identical, and strain LMM_E3T was chosen as a representative and characterized further. Phylogenetic analysis based on 16S rRNA gene sequences clustered this isolate inside the genus Bifidobacterium and showed the highest levels of sequence similarity with B. lemurum DSM 28807T (99.3 %), with Bifidobacterium pullorum LMG 21816T and Bifidobacterium longum subsp. infantis ATCC 15697T (96.4 and 96.3 %, respectively) as the next most similar strains. The hsp60 gene sequence of strain LMM_E3T showed the highest similarity to that of Bifidobacterium stellenboschense DSM 23968T (93.3 %), and 91.0 % similarity to that of the type strain of B. lemurum. DNA-DNA reassociation with the closest neighbour B. lemurum DSM 28807T was found to be 65.4 %. The DNA G+C content was 62.3 mol%. Strain LMM_E3T showed a peptidoglycan structure that has not been detected in bifidobacteria so far: A3alpha l-Lys-l-Ser-l-Thr-l-Ala. Based on the phylogenetic, genotypic and phenotypic data, strain LMM_E3T represents a novel species within the genus Bifidobacterium, for which the name Bifidobacterium eulemuris sp. nov. is proposed; the type strain is LMM_E3T ( = DSM 100216T = JCM 30801T). PMID- 26823375 TI - Reply to 'Sudden Cardiac Death Following Use of the Synthetic Cannabinoid MDMB CHMICA'. PMID- 26823376 TI - Successful haemostatic management of replacement of the ascending aorta for type A acute aortic dissection in a patient with mild haemophilia B. PMID- 26823374 TI - Homology modeling and docking studies of ENPP4: a BCG activated tumoricidal macrophage protein. AB - BACKGROUND: The 3D structure and functions of ENPP4, a protein expressed on the surface of Bacillus Calmette-Guerin (BCG)-activated macrophages, are unknown. In this study, we analyzed the 3D structure of ENPP4 and determined its tumoricidal effects on MCA207 cells. RESULTS: Homology modeling showed that Arg305, Tyr341, Asn291, and Asn295 are important residues in substrate, adenosine triphosphate (ATP), binding. A molecular dynamics study was also carried out to study the stability of ENPP4 (including zinc atoms) as well as its ligand-enzyme complex. BCG increased ENPP4 expression in macrophages, and specific blocking of ENPP4 in BCG-activated macrophages (BAMs) significantly reduced their cytotoxicity against MCA207 cells. CONCLUSIONS: These results indicate that zinc remains inside the ENPP4 protein, a BCG activated tumoricidal macrophage protein, throughout the simulation. Important information for the design of new inhibitors was obtained. PMID- 26823377 TI - Evolutionary potential for increased invasiveness: High-Performance Polygonum cespitosum genotypes are competitively superior in full sun. AB - PREMISE OF STUDY: The presence of genetic variation for traits that contribute to ecological range expansion can provide the potential for introduced taxa to evolve greater invasiveness. Genotypes that contribute to the spread of introduced range populations must have the ability to maintain fitness under changing environmental stress and competitive intensity. Previously, we identified a subset of genotypes in populations of the invasive annual Polygonum cespitosum that express consistently high reproductive fitness in diverse (shaded, dry, and resource-rich) conditions. Here, we investigated whether these broadly adaptive (High-Performance) genotypes also show a competitive advantage over conspecifics in full sun and/or shade. METHODS: We grew a population balanced sample of 13 High-Performance and 13 'Control' genotypes in intraspecific competitive arrays, comprising all four possible combinations of High-Performance vs. Control target plants and competitive backgrounds, in both full sun and shaded glasshouse environments. KEY RESULTS: In full sun, High Performance genotypes (1) better maintained growth and reproductive output despite competition and (2) more strongly suppressed growth and reproduction of target plants. However, genotypes did not differ significantly in shade. CONCLUSIONS: Competitive superiority in open conditions may contribute to increasing predominance of these broadly adapted genotypes in introduced-range Polygonum cespitosum populations, and hence to the evolution of greater invasiveness. This study provides insight into the role of genotypic variation for ecological traits in the range expansion of a contemporary plant invader. It also highlights how such variation can be differently expressed in alternative environments (gene by environment interaction). PMID- 26823379 TI - The remarkable repeated evolution of herbicide resistance. PMID- 26823378 TI - Water uptake of Alaskan tundra evergreens during the winter-spring transition. AB - PREMISE OF THE STUDY: The cold season in the Arctic extends over 8 to 9 mo, yet little is known about vascular plant physiology during this period. Evergreen species photosynthesize under the snow, implying that they are exchanging water with the atmosphere. However, liquid water available for plant uptake may be limited at this time. The study objective was to determine whether evergreen plants are actively taking up water while under snow and/or immediately following snowmelt during spring thaw. METHODS: In two in situ experiments, one at the plot level and another at the individual species level, (2)H-labeled water was used as a tracer injected beneath the snow, after which plant stems and leaves were tested for the presence of the label. In separate experiments, excised shoots of evergreen species were exposed to (2)H-labeled water for ~5 s or 60 min and tested for foliar uptake of the label. KEY RESULTS: In both the plot-level and the species-level experiments, some (2)H-labeled water was found in leaves and stems. Additionally, excised individual plant shoots exposed to labeled water for 60 min took up significantly more (2)H-label than shoots exposed ~5 s. CONCLUSIONS: Evergreen tundra plants take up water under snow cover, some via roots, but also likely by foliar uptake. The ability to take up water in the subnivean environment allows evergreen tundra plants to take advantage of mild spring conditions under the snow and replenish carbon lost by winter respiration. PMID- 26823380 TI - Engineering Metallic Nanoparticles for Enhancing and Probing Catalytic Reactions. AB - Recent developments in tailoring the structural and chemical properties of colloidal metal nanoparticles (NPs) have led to significant enhancements in catalyst performance. Controllable colloidal synthesis has also allowed tailor made NPs to serve as mechanistic probes for catalytic processes. The innovative use of colloidal NPs to gain fundamental insights into catalytic function will be highlighted across a variety of catalytic and electrocatalytic applications. The engineering of future heterogenous catalysts is also moving beyond size, shape and composition considerations. Advancements in understanding structure-property relationships have enabled incorporation of complex features such as tuning surface strain to influence the behavior of catalytic NPs. Exploiting plasmonic properties and altering colloidal surface chemistry through functionalization are also emerging as important areas for rational design of catalytic NPs. This news article will highlight the key developments and challenges to the future design of catalytic NPs. PMID- 26823381 TI - Crosslinked Remote-Doped Hole-Extracting Contacts Enhance Stability under Accelerated Lifetime Testing in Perovskite Solar Cells. AB - A crosslinked hole-extracting electrical contact is reported, which simultaneously improves the stability and lowers the hysteresis of perovskite solar cells. Polymerizable monomers and crosslinking processes are developed to obviate in situ degradation of the under lying perovskite. The crosslinked material is band-aligned with perovskite. The required free carrier density is induced by a high-work-function metal oxide layer atop the device, following a remote-doping strategy. PMID- 26823382 TI - A Novel Feed-Forward Modeling System Leads to Sustained Improvements in Attention and Academic Performance. AB - OBJECTIVE: This study tested a novel feed-forward modeling (FFM) system as a nonpharmacological intervention for the treatment of ADHD children and the training of cognitive skills that improve academic performance. METHOD: This study implemented a randomized, controlled, parallel design comparing this FFM with a nonpharmacological community care intervention. Improvements were measured on parent- and clinician-rated scales of ADHD symptomatology and on academic performance tests completed by the participant. Participants were followed for 3 months after training. RESULTS: Participants in the FFM training group showed significant improvements in ADHD symptomatology and academic performance, while the control group did not. Improvements from FFM were sustained 3 months later. CONCLUSION: The FFM appeared to be an effective intervention for the treatment of ADHD and improving academic performance. This FFM training intervention shows promise as a first-line treatment for ADHD while improving academic performance. PMID- 26823383 TI - Comparison of Performance on ADHD Quality of Care Indicators: Practitioner Self Report Versus Chart Review. AB - OBJECTIVE: This study compared practitioner self-report of ADHD quality of care measures with actual performance, as documented by chart review. METHOD: In total, 188 practitioners from 50 pediatric practices completed questionnaires in which they self-reported estimates of ADHD quality of care indicators. A total of 1,599 charts were reviewed. RESULTS: The percentage of patients for whom practitioners self-reported that they used evidence-based care was higher in every performance category when compared with chart review, including higher use of parent and teacher rating scales during assessment and treatment compared with chart review. Self-reported use of Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria during assessment was also higher than by chart review. The actual number of days until the first contact after starting medication was nearly three times longer than self-report estimates. CONCLUSION: Practitioners overreport performance on quality of care indicators. These differences were large and consistent across ADHD diagnostic and treatment monitoring practices. Practitioner self-report of ADHD guideline adherence should not be considered a valid measure of performance. PMID- 26823385 TI - Comparison of fluorescence in-situ hybridisation with dual-colour in-situ hybridisation for assessment of HER2 gene amplification of breast cancer in Hong Kong. AB - OBJECTIVES: To compare the PathVysion fluorescence in-situ hybridisation assay with the INFORM HER2 Dual in-situ hybridisation assay on 104 invasive breast cancers with a broad spectrum of immunohistochemistry scores. METHODS: This case series involved consecutive patients diagnosed with invasive breast carcinoma with equivocal immunohistochemistry score and referred for further HER2 assessment from the departments of Surgery and/or Clinical Oncology of the two hospitals between January 2013 and February 2014. An additional 10 cases with negative HER2 immunohistochemistry and 11 cases with positive HER2 immunohistochemistry were further included. RESULTS: The results of both fluorescence in-situ hybridisation and dual in-situ hybridisation were available in 99 of 104 cases, respectively. Student'st test showed no statistically significant difference in the mean number of HER2 count, CEP17 copies, or HER2/CEP17 ratio between that obtained by fluorescence in-situ hybridisation and that obtained by dual in-situ hybridisation. Pearson's correlation of results for the two assays was strong for HER2/CEP17 signal ratio (R=0.963, P<0.001) and mean HER2 copies per nucleus (R=0.897, P<0.001). Overall agreement was 96.0% (95 out of 99 cases, K0.882). Three of the four discordant cases were equivocal for either fluorescence in-situ hybridisation or dual in-situ hybridisation. The results of immunohistochemistry 0/1+ and 3+ cases showed 100% concordance between the two assays. The failure rate was 0.96% for fluorescence in-situ hybridisation and 3.85% for dual in-situ hybridisation. Cases that failed for fluorescence in situ hybridisation were successful for dual in-situ hybridisation and vice versa. CONCLUSIONS: Our study showed that dual in-situ hybridisation is a reliable and useful option for HER2 testing in breast cancer. PMID- 26823384 TI - Muscarinic receptor subtypes differentially control synaptic input and excitability of cerebellum-projecting medial vestibular nucleus neurons. AB - Neurons in the vestibular nuclei have a vital function in balance maintenance, gaze stabilization, and posture. Although muscarinic acetylcholine receptors (mAChRs) are expressed and involved in regulating vestibular function, it remains unclear how individual mAChR subtypes regulate vestibular neuronal activity. In this study, we determined which specific subtypes of mAChRs control synaptic input and excitability of medial vestibular nucleus (MVN) neurons that project to the cerebellum. Cerebellum-projecting MVN neurons were labeled by a fluorescent retrograde tracer and then identified in rat brainstem slices. Quantitative PCR analysis suggested that M2 and M3 were the possible major mAChR subtypes expressed in the MVN. The mAChR agonist oxotremorine-M significantly reduced the amplitude of glutamatergic excitatory post-synaptic currents evoked by stimulation of vestibular primary afferents, and this effect was abolished by the M2-preferring antagonist AF-DX 116. However, oxotremorine-M had no effect on GABA mediated spontaneous inhibitory post-synaptic currents of labeled MVN neurons. Furthermore, oxotremorine-M significantly increased the firing activity of labeled MVN neurons, and this effect was blocked by the M3-preferring antagonist J104129 in most neurons tested. In addition, AF-DX 116 reduced the onset latency and prolonged the excitatory effect of oxotremorine-M on the firing activity of labeled MVN neurons. Our findings suggest that M3 is the predominant post synaptic mAChR involved in muscarinic excitation of cerebellum-projecting MVN neurons. Pre-synaptic M2 mAChR regulates excitatory glutamatergic input from vestibular primary afferents, which in turn influences the excitability of cerebellum-projecting MVN neurons. This new information has important therapeutic implications for treating vestibular disorders with mAChR subtype-selective agents. Medial vestibular nucleus (MVN) neurons projecting to the cerebellum are involved in balance control. We found that activation of pre-synaptic M2 muscarinic receptors inhibit glutamatergic input from vestibular primary afferents, whereas stimulation of post-synaptic M3 muscarinic receptors increases the firing activity of cerebellum-projecting MVN neurons. This new information advances our understanding of the cholinergic mechanism regulating the vestibular system. PMID- 26823386 TI - Haemodynamic changes in emergency department patients with poorly controlled hypertension. AB - OBJECTIVES: This study aimed to measure cardiac output, systemic vascular resistance, cardiac index, and systemic vascular resistance index in emergency department patients with poorly controlled hypertension; and to determine the frequency in which antihypertensive drugs prescribed do not address the predominant haemodynamic abnormality. METHODS: This cross-sectional observational study was conducted in an emergency department of a 1400-bed tertiary hospital in Hong Kong. Patients aged 18 years or above, with systolic blood pressure of >=160 mm Hg or diastolic blood pressure of >=100 mm Hg based on two or more measurements and on two separate occasions within 2 to 14 days, were included. Haemodynamic measurements were obtained using a non-invasive Doppler ultrasound monitor. Doctors were blinded to the haemodynamic data. Any antihypertensive medication adjustment was evaluated for correlation with haemodynamic changes. RESULTS: Overall, 164 patients were included. Their mean age was 69.0 years and 97 (59.1%) were females. Systemic vascular resistance and cardiac output were elevated in 65.8% (95% confidence interval, 57.9-72.9%) and 15.8% (10.8-22.5%) of patients, respectively. Systemic vascular resistance index and cardiac index were elevated in 43.9% (95% confidence interval, 36.2-51.8%) and 19.5% (13.9-26.5%) of patients, respectively. Of 71 patients in whom antihypertensive medications were adjusted, 25 (35.2%; 95% confidence interval, 24.5-47.5%) were prescribed agents that did not correlate with the primary haemodynamic abnormality. CONCLUSIONS: The profile of haemodynamic changes in emergency department patients with poorly controlled hypertension is characterised. The antihypertensive drugs prescribed did not correspond to the patient's primary haemodynamic derangement in 35% of cases. PMID- 26823387 TI - The Influence of Stressor Exposure and Psychosocial Resources on the Age-Anger Relationship. AB - OBJECTIVES: This study examined the processes linking age, stressor exposure, psychosocial coping resources, and two dimensions of anger proneness (i.e., experienced anger and expressed anger). METHOD: Longitudinal change regression analysis of data from a two-wave community panel study including a sample of people aged 18 to 93 ( N = 1,473) is performed. RESULTS: Age is significantly associated with declines in both experienced anger and expressed anger over the 3 year study period. These associations are substantially mediated by the lower levels of chronic stressors and discrimination-related stressors experienced among older adults. In contrast, self-esteem amplifies the association between age and expressed anger. DISCUSSION: These findings clarify the circumstances in which age matters most for changes over time in the experience and expression of anger. They highlight how certain forms of stressor exposure and psychosocial resources are linked with anger proneness and in ways that vary by age. PMID- 26823388 TI - Cardiac symptoms before sudden cardiac death caused by hypertrophic cardiomyopathy: a nationwide study among the young in Denmark. AB - AIMS: Hypertrophic cardiomyopathy (HCM) is a frequent cause of sudden cardiac death (SCD) among the young (SCDY). The aim of this study was to characterize symptoms before SCDY due to HCM. METHODS AND RESULTS: Through review of all death certificates, we identified all SCDs in Danes aged 1-35 years in 2000-2009. Nationwide we included all deaths (n = 8756) and identified 431 autopsied SCDYs. All available records from hospitals and general practitioners were retrieved. To compare symptoms, we included a control groups consisting of traffic accident victims (n = 74). In the 10-year study period, 431 autopsied SCDY cases were reviewed and 38 cases (9%) were included, of which 22 (58%) had morphologic findings diagnostic of HCM and 16 (42%) had findings suggestive, but not diagnostic, of HCM ('possible HCM'). Cardiac symptoms >1 h prior to death were reported in 21 (55%) of cases, and 16 (42%) sought medical attention. One (1%) control had cardiac symptoms before death. Consequently, a significantly higher proportion of cases had cardiac symptoms before death and cases more often sought medical attention than controls (P < 0.001). CONCLUSION: In conclusion, this nationwide study demonstrates a high frequency of cardiac symptoms prior to death in SCDY cases who died of HCM, as 55% had cardiac symptoms and nearly half of the cases sought medical attention. PMID- 26823390 TI - Ki-67 is required for maintenance of cancer stem cells but not cell proliferation. AB - Ki-67 expression is correlated with cell proliferation and is a prognostic marker for various cancers; however, its function is unknown. Here we demonstrate that genetic disruption of Ki-67 in human epithelial breast and colon cancer cells depletes the cancer stem cell niche. Ki-67 null cells had a proliferative disadvantage compared to wildtype controls in colony formation assays and displayed increased sensitivity to various chemotherapies. Ki-67 null cancer cells showed decreased and delayed tumor formation in xenograft assays, which was associated with a reduction in cancer stem cell markers. Immunohistochemical analyses of human breast cancers revealed that Ki-67 expression is maintained at equivalent or greater levels in metastatic sites of disease compared to matched primary tumors, suggesting that maintenance of Ki-67 expression is associated with metastatic/clonogenic potential. These results elucidate Ki-67's role in maintaining the cancer stem cell niche, which has potential diagnostic and therapeutic implications for human malignancies. PMID- 26823391 TI - Fracture faces of frozen membranes: 50th anniversary. AB - In 1961, the development of an improved freeze-etching (FE) procedure to prepare rapidly frozen biological cells or tissues for electron microscopy raised two important questions. How does a frozen cell membrane fracture? What do the extensive face views of the cell's membranes exposed by the fracture process of FE tell us about the overall structure of biological membranes? I discovered that all frozen membranes tend to split along weakly bonded lipid bilayers. Consequently, the fracture process exposes internal membrane faces rather than either of the membrane's two external surfaces. During etching, when ice is allowed to sublime after fracturing, limited regions of the actual membrane surfaces are revealed. Examination of the fractured faces and etched surfaces provided strong evidence that biological membranes are organized as lipid bilayers with some proteins on the surface and other proteins extending through the bilayer. Membrane splitting made it possible for electron microscopy to show the relative proportion of a membrane's area that exists in either of these two organizational modes. PMID- 26823389 TI - QT interval variability in body surface ECG: measurement, physiological basis, and clinical value: position statement and consensus guidance endorsed by the European Heart Rhythm Association jointly with the ESC Working Group on Cardiac Cellular Electrophysiology. AB - This consensus guideline discusses the electrocardiographic phenomenon of beat-to beat QT interval variability (QTV) on surface electrocardiograms. The text covers measurement principles, physiological basis, and clinical value of QTV. Technical considerations include QT interval measurement and the relation between QTV and heart rate variability. Research frontiers of QTV include understanding of QTV physiology, systematic evaluation of the link between QTV and direct measures of neural activity, modelling of the QTV dependence on the variability of other physiological variables, distinction between QTV and general T wave shape variability, and assessing of the QTV utility for guiding therapy. Increased QTV appears to be a risk marker of arrhythmic and cardiovascular death. It remains to be established whether it can guide therapy alone or in combination with other risk factors. QT interval variability has a possible role in non-invasive assessment of tonic sympathetic activity. PMID- 26823393 TI - Long-term outcome after topical ciclosporin in severe dry eye disease with a 10 year follow-up. AB - AIM: To report a 10-year follow-up of patients suffering from severe dry eye syndrome (DES) initially treated with topical ciclosporin A (tCSA) for 6 months. METHODS: The charts of 26 patients with severe DES related to keratoconjunctivitis sicca (KCS) and followed for a minimum 10-year follow-up were retrospectively reviewed. All of them were treated initially with tCSA for 6 months. The Schirmer I test, fluorescein and lissamine green staining scores and tear film break-up time (TBUT) were recorded to assess clinical symptoms before, during and after treatment. The subjective signs were evaluated with the ocular surface disease index (OSDI) questionnaire. Prolongation and reintroduction of tCSA after the initial treatment and combined treatments were also noted. RESULTS: Overall the median (IQR) duration of tCSA treatment was 23 (7-51) months after a prolonged induction treatment lasting 20 (8-41) months during the 10-year follow-up. For symptoms, a statistically significant difference in the OSDI between baseline and the end of the 10-year follow-up was not found (p=0.67). We noted a statistically significant improvement in all clinical signs after the initial treatment period, still present at the end of follow-up. Only 6.5% of the patients needed reintroduction of tCSA after their prolonged induction treatment. CONCLUSIONS: The improvement observed after an initial tCSA treatment was sustained after a long-term follow-up with few cases requiring additional tCSA treatment. A prolonged induction treatment to decrease initial inflammatory local signs is a promising option in KCS. PMID- 26823392 TI - From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutations. AB - More than 2000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) have been described that confer a range of molecular cell biological and functional phenotypes. Most of these mutations lead to compromised anion conductance at the apical plasma membrane of secretory epithelia and cause cystic fibrosis (CF) with variable disease severity. Based on the molecular phenotypic complexity of CFTR mutants and their susceptibility to pharmacotherapy, it has been recognized that mutations may impose combinatorial defects in CFTR channel biology. This notion led to the conclusion that the combination of pharmacotherapies addressing single defects (e.g., transcription, translation, folding, and/or gating) may show improved clinical benefit over available low-efficacy monotherapies. Indeed, recent phase 3 clinical trials combining ivacaftor (a gating potentiator) and lumacaftor (a folding corrector) have proven efficacious in CF patients harboring the most common mutation (deletion of residue F508, DeltaF508, or Phe508del). This drug combination was recently approved by the U.S. Food and Drug Administration for patients homozygous for DeltaF508. Emerging studies of the structural, cell biological, and functional defects caused by rare mutations provide a new framework that reveals a mixture of deficiencies in different CFTR alleles. Establishment of a set of combinatorial categories of the previously defined basic defects in CF alleles will aid the design of even more efficacious therapeutic interventions for CF patients. PMID- 26823394 TI - Characteristics and quantification of vascular changes in macular telangiectasia type 2 on optical coherence tomography angiography. AB - BACKGROUND: Macular telangiectasia type 2 (MacTel 2) is a bilateral idiopathic, rare neurodegenerative disease with alterations in the macular capillary network leading to vision loss and is the most common of three subtypes. Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality which helps understand the complex pathological changes, and images the blood vessels across different layers based on their flow characteristics. METHODS: A cross sectional study was conducted on 56 eyes of Asian Indian eyes of 28 consecutive patients with MacTel 2 studied during a 3-month period in a tertiary eye care hospital of South India. Clinically diagnosed cases of MacTel 2 underwent fundus photography, spectral domain OCT and OCTA. Fluorescein angiography was performed only when clinically indicated. Mean capillary density was calculated using a MATLAB-based automated software. The images were thresholded and binarised to derive the mean value. RESULTS: The mean age at presentation was 60+/-5.2, with a female preponderance of 71.42%. Vascular network on OCTA shows an increase in the intervascular spaces with progressive capillary rarefaction and abnormal capillary anastomosis. The outer retina and choroid were involved during the later stages and showed a prominent vascular network. The mean capillary density of the superficial and deep layers was 39.99% and 39.03% as against 45.18% and 44.21% in the controls, respectively. There was a statistically significant difference between the two groups (p<0.01). There is a positive and statistically significant correlation between the superficial and deep layers. CONCLUSION: OCTA helps understand the pathology and disease progression better in MacTel 2. PMID- 26823395 TI - The ophthalmic presentation of Hermansky-Pudlak syndrome 6. AB - BACKGROUND: Hermansky-Pudlak syndrome (HPS) may present to the ophthalmologist with signs suggestive of oculocutaneous albinism. Consideration of HPS as a differential diagnosis is important due to its potential systemic complications. HPS6 is a rarely reported subtype. METHODS: Three patients from two families underwent clinical examination, imaging and targeted systemic investigations. Electrophysiology with visual-evoked potentials (VEPs) was performed in both children of family 1. Whole exome sequencing (WES) was performed on the proband of family 1. Bidirectional Sanger sequencing of the single exon and intron-exon boundaries of HPS6 was performed on all affected patients and segregation confirmed in available relatives. RESULTS: Two siblings presented in infancy with nystagmus and reduced vision. They were initially diagnosed with isolated foveal hypoplasia with no aberrant chiasmal misrouting on VEPs. WES performed in the proband when 10 years of age identified a novel homozygous missense variant in HPS6 and further questioning elicited a history of nose bleeds and mild bruising. Segregation supported causality of this variant in the affected younger sibling. In the third unrelated patient, an initial diagnosis of ocular albinism was made at 3 months with HPS only diagnosed at 26 years. Biallelic, truncating mutations in HPS6 were identified by candidate Sanger sequencing and included a novel variant. Abnormal platelet function consistent with HPS was confirmed in all patients. CONCLUSIONS: The diagnosis of HPS in all patients was delayed due to a mild systemic phenotype. Next-generation sequencing can aid diagnosis of syndromic conditions with important consequences for preventing morbidity. PMID- 26823396 TI - Optical coherence tomography angiography and indocyanine green angiography for corneal vascularisation. AB - BACKGROUND/AIM: To describe an optical coherence tomography angiography (OCTA) system adapted for anterior segment imaging, compared with indocyanine green angiography (ICGA) in eyes with corneal vascularisation. METHODS: Retrospective study of subjects with corneal vascularisation secondary to microbial keratitis who had OCTA scans performed using a commercially available split-spectrum amplitude-decorrelation algorithm angiography system (AngioVue; Optovue Inc., Fremont, California, USA) and ICGA images (Spectralis; Heidelberg Engineering, Heidelberg, Germany). The agreement between OCTA and ICGA techniques in terms of area of vascularisation measured, using Bland-Altman 95% limits of agreement (LOA). RESULTS: We compared the area of corneal vascularisation in 64 scan images (eight eyes, four scans for each angiography technique). In our series, the overall mean area of vascularisation from the ICGA scans was 0.49+/-0.34 mm2 and OCTA scans was 0.51+/-0.36 mm2. We obtained substantial repeatability in terms of image quality score (kappa=0.80) for all OCTA scans. The agreement between OCTA and ICGA scans was good, although ICGA measured a smaller area compared with the OCTA with a mean difference of -0.03 mm2 (95% CI -0.07 to 0.01). The LOA ranged from a lower limit of -0.27 (95% CI -0.34 to -0.19) to an upper limit of 0.20 (95% CI 0.13 to 0.28, p=0.127). CONCLUSIONS: We found that rapid, non-contact OCTA adapted for the cornea was comparable with ICGA for measurement of the area of corneal vascularisation in this pilot clinical study. Further prospective studies are required to confirm if this relatively new imaging technique may be further developed to replace invasive angiography techniques for the anterior segment. PMID- 26823397 TI - Relationship of retinal vascular calibre and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus: the Desheng Diabetic Eye Study. AB - AIMS: To describe the relationship of retinal arteriolar and venular calibre with diabetic retinopathy (DR) and related risk factors, including glucose levels and other biomarkers in a Chinese population with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study. Patients with T2DM were recruited from a local community in urban Beijing. Seven fields 30 degrees colour fundus photographs were taken and examined for the presence and severity of DR using a standardised grading system. Retinal vascular calibres were measured and expressed as average central retinal arteriolar and venular equivalent using a computer-based program. RESULTS: A total of 1340 patients with T2DM were included for analysis. Of these, 472 (35.22%) had DR. Wider retinal venular calibre, but not arteriolar calibre, was associated with increasing glucose and glycosylated haemoglobin A1c levels (p<0.006) and dyslipidaemia (p for trend <0.05). After adjusting for possible covariates, the higher quartile of retinal venular calibre was associated with higher prevalence of any DR (OR 2, 95% CI 1.36 to 2.95). Venular calibre increased from 224.33 MUm in those without retinopathy to 231.21 MUm in those with mild, 241.01 MUm in those with moderate and 235.65 MUm in those with severe retinopathy (p for trend <0.001). Arteriolar calibre was not associated with DR. CONCLUSIONS: In the current study, wider venular calibre, but not arteriolar calibre, was shown to be associated with development and increased severity of DR independently from other risk factors in a Chinese diabetic population. PMID- 26823398 TI - In vivo confocal microscopy of inflammatory cells in the corneal subbasal nerve plexus in patients with different subtypes of anterior uveitis. AB - PURPOSE: Previously we could show increased numbers and densities of dendritic like cells (DLCs) in the subbasal nerve plexus of the central cornea in patients with herpetic anterior uveitis (HAU). Now we aimed to explore these and other inflammatory cells seen in this layer in different subtypes of anterior uveitis using in vivo confocal microscopy. METHODS: Consecutive eyes of patients with different types of anterior uveitis, HAU, Fuchs' uveitis syndrome (FUS), juvenile idiopathic arthritis (JIA) and human leucocyte antigen (HLA)-B27-related anterior uveitis were examined in vivo with the combination of Heidelberg Retina Tomograph II/III and Rostock Cornea Module. The contralateral eye was used as control. Inflammatory cells were defined on the basis of their morphology: type 1 (DLCs) and type 2 (cell bodies lacking dendrites). Frequencies were evaluated statistically in each group. RESULTS: The difference between means of type 1 cells density of affected eyes in all four groups was significant (one-way analysis of variance (ANOVA) p=0.039). The difference between means of type 1 cell densities of affected eyes in patients with HAU (96.8+/-44.2 cells/mm2, n=10) and that of patients with FUS (46.4+/-38.7 cells/mm2, n=17) was significant (Tukey's post hoc p=0.025), whereas the difference between patients with HAU and JIA (53.3+/-34.5 cells/mm2, n=7) and patients with HAU and HLA-B27 (63.1+/-59.2 cells/mm2, n=10) was not significant (Tukey's post hoc p=0.181 and 0.300). In contrast, the following means resulted from the evaluation of type 2 cells: the difference between means of affected eyes in all four groups was not significant (one-way ANOVA p=0.185). Density means difference of patients with HAU (44.9+/ 22.6 cells/mm2, n=5) and that of FUS (20.0+/-11.0 cells/mm2, n=2) and that of patients with JIA (56.0+/-18.3 cells/mm2, n=2) and that of HLA-B27 (36.1+/-24.1 cells/mm2, n=5) was not significant (Tukey's post hoc p=0.302, 0.877 and 0.739). The contralateral eye of all patient groups showed also an inflammatory cell infiltrate of lesser extent. CONCLUSIONS: The high density and morphology of DLCs in the central cornea of patients with HAU assessed by confocal microscopy supports the clinical diagnosis of HAU especially when compared with patients with FUS but not when compared with patients with JIA or HLA-B27. CLINICAL RELEVANCE: This study suggests that the non-invasive confocal microscopy of the cornea is capable of supporting a clinical diagnosis in patients with uveitis. PMID- 26823399 TI - Predictive value of prostate specific antigen in a European HIV-positive cohort: does one size fit all? AB - BACKGROUND: It is common practice to use prostate specific antigen (PSA) >=4.0 ng/ml as a clinical indicator for men at risk of prostate cancer (PCa), however, this is unverified in HIV+ men. We aimed to describe kinetics and predictive value of PSA for PCa in HIV+ men. METHODS: A nested case control study of 21 men with PCa and 40 matched-controls within EuroSIDA was conducted. Prospectively stored plasma samples before PCa (or matched date in controls) were measured for the following markers: total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG). Conditional logistic regression models investigated associations between markers and PCa. Mixed models were used to describe kinetics. Sensitivity and specificity of using tPSA >4 ng/ml to predict PCa was calculated. Receiver operating characteristic curves were used to identify optimal cutoffs in HIV+ men for total PSA. RESULTS: 61 HIV+ men were included with a median 6 (IQR 2-9) years follow-up. Levels of tPSA increased by 13.7% per year (95% CI 10.3, 17.3) in cases, but was stable in controls (-0.4%; 95% CI -2.5, 1.7). Elevated PSA was associated with higher odds of PCa at first (OR for twofold higher 4.7; 95% CI 1.7, 12.9; P<0.01) and last sample (8.1; 95% CI 1.1, 58.9; P=0.04). A similar relationship was seen between fPSA and PCa. Testosterone and SHBG level were not associated with PCa. tPSA level >4 ng/ml had 99% specificity and 38% sensitivity. The optimal PSA cutoff was 1.5 ng/ml overall (specificity =84%, sensitivity =81%). CONCLUSIONS: PSA was highly predictive of PCa in HIV+ men; however, the commonly used PSA>4 ng/ml to indicate high PCa risk was not sensitive in our population and use of the lower cutoff of PSA>1.5 ng/ml warrants consideration. PMID- 26823400 TI - In vitro construction and in vivo regeneration of esophageal bilamellar muscle tissue. AB - In order to induce esophageal muscle cells' orientation, the silicon wafer with prototype 1 and prototype 2 was designed. Prototype 1 has micro-channels of 200 um width and 30 um depth with 30 um wide wall as the interval. Prototype 2 has channels of 100 um width and 30 um depth with a discontinuous wall which has 30 um gap for each 100 um channel. The poly(ester urethane) scaffolds with pattern prototype 1 and prototype 2 were fabricated using solution casting method and abbreviated as PU1 and PU2, respectively. Silk fibroin was grafted individually on PU1 and PU2 surface (PU1-SF, PU2-SF) using our previous protocol, aiming at improving scaffolds' biocompatibility. The primary esophageal smooth muscle cell was seeded to evaluate the scaffolds' cytocompatibility in vitro. Characterizations like MTT assay, immunocytochemistry, scanning electron microscope, and Western blotting were applied. After that, poly(ester urethane) scaffolds with double patterns, prototype 1 on the exterior, and prototype 2 in the lumen were implanted into the rabbit esophagous to test the regeneration of the muscle tissue. Results from these preliminary tests showed that the growth and differentiation of primary smooth muscle cells were promoted, but also the muscle tissue with endocircular and exolongitudinal architecture was in regenerating, against non-constitution in the animals without the patterned scaffold or with poly(ester urethane) plane membrane at the defaulted sites. This micro-channel pattern together with silk fibroin grafting and vascular endothelial growth factor coating greatly promoted the regeneration of esophageal muscle with normal histological structure. PMID- 26823401 TI - Cover stories: Making the Babylonian tablet cover. PMID- 26823402 TI - Global science engagement. PMID- 26823404 TI - CLIMATE POLICY. Can Germany engineer a coal exit? PMID- 26823405 TI - GEOCHEMISTRY. Rare isotopes offer clues to the chemistry of the planet. PMID- 26823406 TI - PHYSIOLOGY. A fish back from the dead. PMID- 26823407 TI - INFECTIOUS DISEASE. Researchers claim to find HIV sanctuaries. PMID- 26823408 TI - ARCHAEOLOGY. Ancient Babylonians took first steps to calculus. PMID- 26823409 TI - Tibet's primeval ice. PMID- 26823410 TI - A cancer legacy. PMID- 26823411 TI - EVOLUTION. Avian supergenes. PMID- 26823412 TI - ECOLOGY. How ecosystems change. PMID- 26823413 TI - CONSERVATION ECOLOGY. How can higher-yield farming help to spare nature? PMID- 26823414 TI - MICROBIOME. Prescription drugs obscure microbiome analyses. PMID- 26823415 TI - CANCER. Tracking the origins of tumorigenesis. PMID- 26823416 TI - A necrogenomic registry's potential. PMID- 26823417 TI - Tropical dams: To build or not to build? PMID- 26823418 TI - Comment on "Worldwide evidence of a unimodal relationship between productivity and plant species richness". AB - Fraser et al. (Reports, 17 July 2015, p. 302) report a unimodal relationship between productivity and species richness at regional and global scales, which they contrast with the results of Adler et al. (Reports, 23 September 2011, p. 1750). However, both data sets, when analyzed correctly, show clearly and consistently that productivity is a poor predictor of local species richness. PMID- 26823421 TI - Activation of Cu(111) surface by decomposition into nanoclusters driven by CO adsorption. AB - The (111) surface of copper (Cu), its most compact and lowest energy surface, became unstable when exposed to carbon monoxide (CO) gas. Scanning tunneling microscopy revealed that at room temperature in the pressure range 0.1 to 100 Torr, the surface decomposed into clusters decorated by CO molecules attached to edge atoms. Between 0.2 and a few Torr CO, the clusters became mobile in the scale of minutes. Density functional theory showed that the energy gain from CO binding to low-coordinated Cu atoms and the weakening of binding of Cu to neighboring atoms help drive this process. Particularly for softer metals, the optimal balance of these two effects occurs near reaction conditions. Cluster formation activated the surface for water dissociation, an important step in the water-gas shift reaction. PMID- 26823419 TI - Response to Comment on "Worldwide evidence of a unimodal relationship between productivity and plant species richness". AB - Tredennick et al. criticize one of our statistical analyses and emphasize the low explanatory power of models relating productivity to diversity. These criticisms do not detract from our key findings, including evidence consistent with the unimodal constraint relationship predicted by the humped-back model and evidence of scale sensitivities in the form and strength of the relationship. PMID- 26823422 TI - Enhanced East Pacific Rise hydrothermal activity during the last two glacial terminations. AB - Mid-ocean ridge magmatism is driven by seafloor spreading and decompression melting of the upper mantle. Melt production is apparently modulated by glacial interglacial changes in sea level, raising the possibility that magmatic flux acts as a negative feedback on ice-sheet size. The timing of melt variability is poorly constrained, however, precluding a clear link between ridge magmatism and Pleistocene climate transitions. Here we present well-dated sedimentary records from the East Pacific Rise that show evidence of enhanced hydrothermal activity during the last two glacial terminations. We suggest that glacial maxima and lowering of sea level caused anomalous melting in the upper mantle and that the subsequent magmatic anomalies promoted deglaciation through the release of mantle heat and carbon at mid-ocean ridges. PMID- 26823423 TI - Ancient Babylonian astronomers calculated Jupiter's position from the area under a time-velocity graph. AB - The idea of computing a body's displacement as an area in time-velocity space is usually traced back to 14th-century Europe. I show that in four ancient Babylonian cuneiform tablets, Jupiter's displacement along the ecliptic is computed as the area of a trapezoidal figure obtained by drawing its daily displacement against time. This interpretation is prompted by a newly discovered tablet on which the same computation is presented in an equivalent arithmetical formulation. The tablets date from 350 to 50 BCE. The trapezoid procedures offer the first evidence for the use of geometrical methods in Babylonian mathematical astronomy, which was thus far viewed as operating exclusively with arithmetical concepts. PMID- 26823424 TI - Emergence of superconductivity in the canonical heavy-electron metal YbRh2Si2. AB - The smooth disappearance of antiferromagnetic order in strongly correlated metals commonly furnishes the development of unconventional superconductivity. The canonical heavy-electron compound YbRh2Si2 seems to represent an apparent exception from this quantum critical paradigm in that it is not a superconductor at temperature T >= 10 millikelvin (mK). Here we report magnetic and calorimetric measurements on YbRh2Si2, down to temperatures as low as T ~ 1 mK. The data reveal the development of nuclear antiferromagnetic order slightly above 2 mK and of heavy-electron superconductivity almost concomitantly with this order. Our results demonstrate that superconductivity in the vicinity of quantum criticality is a general phenomenon. PMID- 26823425 TI - Periodic slow slip triggers megathrust zone earthquakes in northeastern Japan. AB - Both aseismic and seismic slip accommodate relative motion across partially coupled plate-boundary faults. In northeastern Japan, aseismic slip occurs in the form of decelerating afterslip after large interplate earthquakes and as relatively steady slip on uncoupled areas of the subduction thrust. Here we report on a previously unrecognized quasi-periodic slow-slip behavior that is widespread in the megathrust zone. The repeat intervals of the slow slip range from 1 to 6 years and often coincide with or precede clusters of large [magnitude (M) >= 5] earthquakes, including the 2011 M 9 Tohoku-oki earthquake. These results suggest that inherently periodic slow-slip events result in periodic stress perturbations and modulate the occurrence time of larger earthquakes. The periodicity in the slow-slip rate has the potential to help refine time-dependent earthquake forecasts. PMID- 26823426 TI - Oxygen isotopic evidence for vigorous mixing during the Moon-forming giant impact. AB - Earth and the Moon are shown here to have indistinguishable oxygen isotope ratios, with a difference in Delta'(17)O of -1 +/- 5 parts per million (2 standard error). On the basis of these data and our new planet formation simulations that include a realistic model for primordial oxygen isotopic reservoirs, our results favor vigorous mixing during the giant impact and therefore a high-energy, high-angular-momentum impact. The results indicate that the late veneer impactors had an average Delta'(17)O within approximately 1 per mil of the terrestrial value, limiting possible sources for this late addition of mass to the Earth-Moon system. PMID- 26823427 TI - Simultaneous covalent and noncovalent hybrid polymerizations. AB - Covalent and supramolecular polymers are two distinct forms of soft matter, composed of long chains of covalently and noncovalently linked structural units, respectively. We report a hybrid system formed by simultaneous covalent and supramolecular polymerizations of monomers. The process yields cylindrical fibers of uniform diameter that contain covalent and supramolecular compartments, a morphology not observed when the two polymers are formed independently. The covalent polymer has a rigid aromatic imine backbone with helicoidal conformation, and its alkylated peptide side chains are structurally identical to the monomer molecules of supramolecular polymers. In the hybrid system, covalent chains grow to higher average molar mass relative to chains formed via the same polymerization in the absence of a supramolecular compartment. The supramolecular compartments can be reversibly removed and re-formed to reconstitute the hybrid structure, suggesting soft materials with novel delivery or repair functions. PMID- 26823428 TI - Airway acidification initiates host defense abnormalities in cystic fibrosis mice. AB - Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. In humans and pigs, the loss of CFTR impairs respiratory host defenses, causing airway infection. But CF mice are spared. We found that in all three species, CFTR secreted bicarbonate into airway surface liquid. In humans and pigs lacking CFTR, unchecked H(+) secretion by the nongastric H(+)/K(+) adenosine triphosphatase (ATP12A) acidified airway surface liquid, which impaired airway host defenses. In contrast, mouse airways expressed little ATP12A and secreted minimal H(+); consequently, airway surface liquid in CF and non-CF mice had similar pH. Inhibiting ATP12A reversed host defense abnormalities in human and pig airways. Conversely, expressing ATP12A in CF mouse airways acidified airway surface liquid, impaired defenses, and increased airway bacteria. These findings help explain why CF mice are protected from infection and nominate ATP12A as a potential therapeutic target for CF. PMID- 26823429 TI - An unprecedented mechanism of nucleotide methylation in organisms containing thyX. AB - In several human pathogens, thyX-encoded flavin-dependent thymidylate synthase (FDTS) catalyzes the last step in the biosynthesis of thymidylate, one of the four DNA nucleotides. ThyX is absent in humans, rendering FDTS an attractive antibiotic target; however, the lack of mechanistic understanding prohibits mechanism-based drug design. Here, we report trapping and characterization of two consecutive intermediates, which together with previous crystal structures indicate that the enzyme's reduced flavin relays a methylene from the folate carrier to the nucleotide acceptor. Furthermore, these results corroborate an unprecedented activation of the nucleotide that involves no covalent modification but only electrostatic polarization by the enzyme's active site. These findings indicate a mechanism that is very different from thymidylate biosynthesis in humans, underscoring the promise of FDTS as an antibiotic target. PMID- 26823430 TI - Most microbe-specific naive CD4+ T cells produce memory cells during infection. AB - Infection elicits CD4(+) memory T lymphocytes that participate in protective immunity. Although memory cells are the progeny of naive T cells, it is unclear that all naive cells from a polyclonal repertoire have memory cell potential. Using a single-cell adoptive transfer and spleen biopsy method, we found that in mice, essentially all microbe-specific naive cells produced memory cells during infection. Different clonal memory cell populations had different B cell or macrophage helper compositions that matched effector cell populations generated much earlier in the response. Thus, each microbe-specific naive CD4(+) T cell produces a distinctive ratio of effector cell types early in the immune response that is maintained as some cells in the clonal population become memory cells. PMID- 26823431 TI - Two genes substitute for the mouse Y chromosome for spermatogenesis and reproduction. AB - The mammalian Y chromosome is considered a symbol of maleness, as it encodes a gene driving male sex determination, Sry, as well as a battery of other genes important for male reproduction. We previously demonstrated in the mouse that successful assisted reproduction can be achieved when the Y gene contribution is limited to only two genes, Sry and spermatogonial proliferation factor Eif2s3y. Here, we replaced Sry by transgenic activation of its downstream target Sox9, and Eif2s3y, by transgenic overexpression of its X chromosome-encoded homolog Eif2s3x. The resulting males with no Y chromosome genes produced haploid male gametes and sired offspring after assisted reproduction. Our findings support the existence of functional redundancy between the Y chromosome genes and their homologs encoded on other chromosomes. PMID- 26823432 TI - Battling the bureaucracy hydra. PMID- 26823434 TI - Erratum for the Research Article "Gating of hippocampal activity, plasticity, and memory by entorhinal cortex long-range inhibition" by J. Basu, J. D. Zaremba, S. K. Cheung, F. L. Hitti, B. V. Zemelman, A. Losonczy, S. A. Siegelbaum. PMID- 26823433 TI - A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation. AB - The "cancerized field" concept posits that cancer-prone cells in a given tissue share an oncogenic mutation, but only discreet clones within the field initiate tumors. Most benign nevi carry oncogenic BRAF(V600E) mutations but rarely become melanoma. The zebrafish crestin gene is expressed embryonically in neural crest progenitors (NCPs) and specifically reexpressed in melanoma. Live imaging of transgenic zebrafish crestin reporters shows that within a cancerized field (BRAF(V600E)-mutant; p53-deficient), a single melanocyte reactivates the NCP state, revealing a fate change at melanoma initiation in this model. NCP transcription factors, including sox10, regulate crestin expression. Forced sox10 overexpression in melanocytes accelerated melanoma formation, which is consistent with activation of NCP genes and super-enhancers leading to melanoma. Our work highlights NCP state reemergence as a key event in melanoma initiation. PMID- 26823436 TI - The Johns Hopkins Bloomberg School of Public Health: A Brief History of a Century of Epidemiologic Discovery. AB - During its first century, the Johns Hopkins University Bloomberg School of Public Health has been home to several faculty members who have played leading roles in defining and expanding the field and science of epidemiology. They have done so by training leaders in the field, creating new methods and applications, and making relevant discoveries in the worlds of infectious and chronic diseases. These methodologic innovations and discoveries underlie many of today's major health policies and practices. PMID- 26823435 TI - Translation from the 5' untranslated region shapes the integrated stress response. AB - Translated regions distinct from annotated coding sequences have emerged as essential elements of the proteome. This includes upstream open reading frames (uORFs) present in mRNAs controlled by the integrated stress response (ISR) that show "privileged" translation despite inhibited eukaryotic initiation factor 2 guanosine triphosphate-initiator methionyl transfer RNA (eIF2.GTP.Met-tRNA(i )(Met)). We developed tracing translation by T cells to directly measure the translation products of uORFs during the ISR. We identified signature translation events from uORFs in the 5' untranslated region of binding immunoglobulin protein (BiP) mRNA (also called heat shock 70-kilodalton protein 5 mRNA) that were not initiated at the start codon AUG. BiP expression during the ISR required both the alternative initiation factor eIF2A and non-AUG-initiated uORFs. We propose that persistent uORF translation, for a variety of chaperones, shelters select mRNAs from the ISR, while simultaneously generating peptides that could serve as major histocompatibility complex class I ligands, marking cells for recognition by the adaptive immune system. PMID- 26823437 TI - A Comprehensive Multistate Model Analyzing Associations of Various Risk Factors With the Course of Breast Cancer in a Population-Based Cohort of Breast Cancer Cases. AB - We employed a semi-Markov multistate model for the simultaneous analysis of various endpoints describing the course of breast cancer. Results were compared with those from standard analyses using a Cox proportional hazards model. We included 3,012 patients with invasive breast cancer newly diagnosed between 2001 and 2005 who were recruited in Germany for a population-based study, the Mamma Carcinoma Risk Factor Investigation (MARIE Study), and prospectively followed up until the end of 2009. Locoregional recurrence and distant metastasis were included as intermediate states, and deaths from breast cancer, secondary cancer, and other causes were included as competing absorbing states. Tumor characteristics were significantly associated with all breast cancer-related endpoints. Nodal involvement was significantly related to local recurrence but more strongly related to distant metastases. Smoking was significantly associated with mortality from second cancers and other causes, whereas menopausal hormone use was significantly associated with reduced distant metastasis and death from causes other than cancer. The presence of cardiovascular disease at diagnosis was solely associated with mortality from other causes. Compared with separate Cox models, multistate models allow for dissection of prognostic factors and intermediate events in the analysis of cause-specific mortality and can yield new insights into disease progression and associated pathways. PMID- 26823438 TI - Body Size, Metabolic Factors, and Risk of Endometrial Cancer in Black Women. AB - Total and abdominal obesity, as well as metabolic factors such as type 2 diabetes, have been associated with a higher risk of endometrial cancer in white women. It remains unclear to what extent these factors influence the risk of endometrial cancer in black women. We followed 47,557 participants from the Black Women's Health Study for incident endometrial cancer from 1995 through 2013 (n = 274). We used Cox regression models to estimate incidence rate ratios and 95% confidence intervals while accounting for potential confounders. Incidence rate ratios for body mass indices (weight (kg)/height (m)(2)) of 25.0-29.9, 30.0-34.9, 35.0-39.9, and >=40.0 versus those <25.0 were 1.00 (95% confidence interval (CI): 0.67, 1.48), 1.49 (95% CI: 0.97, 2.30), 2.16 (95% CI: 1.34, 3.49), and 3.60 (95% CI: 2.24, 5.78), respectively (Ptrend <0.0001). A high weight-to-height ratio was also associated with a higher risk (for the highest quartile vs. the lowest, incidence rate ratio = 2.83, 95% CI: 1.77, 4.53), as was type 2 diabetes mellitus (incidence rate ratio = 1.52, 95% CI: 1.04, 2.21). Positive associations with measures of central adiposity (waist circumference, waist-to-hip ratio, and waist to-height ratio) and hypertension were attenuated after we controlled for body mass index. Total adiposity was an independent risk factor for endometrial cancer among black women and appeared to explain most of the associations seen with other adiposity measures and metabolic factors. PMID- 26823440 TI - Effects of exercise training in patients with chronic obstructive pulmonary disease--a narrative review for FYSS (Swedish Physical Activity Exercise Prescription Book). AB - The aims of this review were to determine the level of evidence for exercise training in the management of patients with chronic obstructive pulmonary disease (COPD) and provide evidence-based recommendations on exercise training. This review was performed in PubMed and Cochrane Library. Included studies investigated patients with COPD who had been randomised to exercise training or no training. Six systematic reviews were included. The methodological quality was scored using a grading system (GRADE). The analysis showed that aerobic and resistance training in patients in a stable state of COPD results in improved health-related quality of life and decreased dyspnoea, anxiety and depression (moderately strong scientific evidence, grade +++), and increased physical capacity and decreased dyspnoea in daily activities (limited scientific evidence, grade ++). In patients with an acute exacerbation, aerobic and resistance training, performed directly after the exacerbation, results in improved health related quality of life (moderately strong scientific evidence, grade +++), improved exercise capacity and decreased mortality and hospitalisation (limited scientific evidence, grade ++). Thus, patients with COPD should be recommended to take part in exercise training. PMID- 26823439 TI - Plasma Biomarkers of Inflammation, the Kynurenine Pathway, and Risks of All Cause, Cancer, and Cardiovascular Disease Mortality: The Hordaland Health Study. AB - We aimed to evaluate 10 biomarkers related to inflammation and the kynurenine pathway, including neopterin, kynurenine:tryptophan ratio, C-reactive protein, tryptophan, and 6 kynurenines, as potential predictors of all-cause and cause specific mortality in a general population sample. The study cohort was participants involved in a community-based Norwegian study, the Hordaland Health Study (HUSK). We used Cox proportional hazards models to assess associations of the biomarkers with all-cause mortality and competing-risk models for cause specific mortality. Of the 7,015 participants, 1,496 deaths were recorded after a median follow-up time of 14 years (1998-2012). Plasma levels of inflammatory markers (neopterin, kynurenine:tryptophan ratio, and C-reactive protein), anthranilic acid, and 3-hydroxykynurenine were positively associated with all cause mortality, and tryptophan and xanthurenic acid were inversely associated. Multivariate-adjusted hazard ratios for the highest (versus lowest) quartiles of the biomarkers were 1.19-1.60 for positive associations and 0.73-0.87 for negative associations. All of the inflammatory markers and most kynurenines, except kynurenic acid and 3-hydroxyanthranilic acid, were associated with cardiovascular disease (CVD) mortality. In this general population, plasma biomarkers of inflammation and kynurenines were associated with risk of all cause, cancer, and CVD mortality. Associations were stronger for CVD mortality than for mortality due to cancer or other causes. PMID- 26823441 TI - Individual socioeconomic status and breast cancer diagnostic stages: a French case-control study. AB - BACKGROUND: Health inequalities have increased over the last 30 years. Our goal was to investigate the relationship between low individual socioeconomic status and poor breast cancer prognosis. Our hypothesis was: low socioeconomic status patients have a higher risk of being diagnosed with late stage breast cancer than high socioeconomic status ones due to delayed diagnosis. METHODS: We conducted a matched case-control study on 619 women with breast cancer, living in the Herault, a French administrative area. Both Cases and Controls were recruited among invasive cases diagnosed in 2011 and 2012 and treated in Herault care centers. Cases were defined as patients with advanced stages. Controls were composed of early stage patients. Individual socioeconomic status was assessed using a validated individual score adapted to the French population and health care system. RESULTS: We observed that low socioeconomic status patients have a 2 fold risk of having late stage breast cancer regardless of cancer characteristics and detection mode (screening vs. clinical signs). CONCLUSION: One reason explaining those results could be that low socioeconomic status patients have less regular follow-up which can lead to later and poorer diagnosis. Follow-up is improved for women with a better awareness of breast cancer. Health policy makers could reduce health inequalities by reducing the delay in breast cancer diagnosis for low socioeconomic status women. PMID- 26823443 TI - Estimating the thermal expansion coefficient of graphene: the role of graphene substrate interactions. AB - The temperature-dependent thermal expansion coefficient of graphene is estimated for as-grown chemical vapor deposited graphene using temperature-dependent Raman spectroscopy. For as-grown graphene on copper, the extent of thermal expansion mismatch between substrate and the graphene layer is significant across the entire measured temperature interval, T = 90-300 K. This mismatch induces lattice strain in graphene. However, graphene grown on copper substrates has a unique morphology in the form of quasi-periodic nanoripples. This crucially influences the profile of the strain in the graphene membrane, which is uniaxial. An estimate of the thermal expansion coefficient of grapheme alpha(T) is obtained after consideration of this strain profile and after incorporating temperature dependent Gruneisen parameter corrections. The value of alpha(T), is found to be negative (average value, -3.75 * 10(-6) K(-1)) for the entire temperature range and it approaches close to zero for T < 150 K. For graphene wet-transferred to three kinds of substrates: copper, poly-dimethylsiloxane, and SiO2/Si, the Raman shifts can largely be modeled with lattice expansion and anharmonic contributions, and the data suggests limited interfacial interaction with the substrate. PMID- 26823444 TI - Optical conductivity of layered calcium cobaltate Ca3Co4O9. AB - We report the optical properties of layered calcium cobaltate, Ca3Co4O9, which is regarded as a promising candidate for use as a thermoelectric material. The optical conductivity shows three broad peaks related to the inter-band transition below 4 eV, which are quite similar to those in the spectra of Na x CoO2. This similarity implies that the CoO2 layer, which is an essential unit for both Ca3Co4O9 and Na x CoO2, is dominant in the energy band structure below 4 eV. In addition, we estimate the effective carrier number per Co site and find similarity between the CoO2 layers of Ca3Co4O9 and Na0.75CoO2, which is consistent with the similarity in their Seebeck coefficients. To discuss the contribution of the rocksalt-type Ca2CoO3 layer in Ca3Co4O9, we propose the concept of optical sheet conductivity in the layered materials and estimate its value in the Ca2CoO3 layer. A comparison with the spin-polarized band calculation of the LDA + Hubbard U formalism with U = 5 eV suggests that the Ca2CoO3 layer has the inter-band transition of 2.6 eV in the spin-down band structure. Evaluation of the valences of Co 3d orbitals indicates the existence of charge transfer from the Ca2CoO3 layer to the CoO2 layer and mixing of Co(3+) and Co(4+) in the CoO2 layer, which may be the origin of the large thermoelectric effect. PMID- 26823442 TI - Workplace social capital and risk of long-term sickness absence. Are associations modified by occupational grade? AB - BACKGROUND: Workplace social capital (WSC) is an emerging topic among both work environment professionals and researchers. We examined (i) whether high WSC protected against risk of long-term sickness absence (LTSA) in a random sample of the Danish workforce during a 1-year follow-up and (ii) whether the association of WSC with sickness absence was modified by occupational grade. METHODS: We measured WSC by self-report in a cohort of 3075 employees and linked responses to a national register of sickness absence. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) of onset of LTSA (>=21 days), adjusted for covariates. We stratified analyses by occupational grade and examined if there was an interaction effect of WSC and occupational grade. RESULTS: A one standard deviation higher WSC score predicted a reduced risk of sickness absence after adjustment for sociodemographic variables, prevalent health problems and health behaviours (HR = 0.85, 95% CI = 0.74-0.99). The HR was attenuated and lost statistical significance after further adjustment for occupational grade (HR = 0.90, 95% CI = 0.78-1.04). When stratified by occupational grade, high WSC predicted a decreased risk of sickness absence among higher grade workers (HR = 0.61, 95% CI = 0.44-0.84) but not among lower grade workers (HR = 0.98, 95% CI = 0.83-1.15). The interaction effect of WSC and occupational grade was statistically significant (HR = 0.97, 95% CI = 0.95-0.99). CONCLUSION: High WSC might reduce risk of LTSA. However, the protective effect appears to be limited to workers of higher occupational grade. PMID- 26823445 TI - Waddling on the Dark Side: Ambient Light Affects Attendance Behavior of Little Penguins. AB - Visible light on Earth largely comes from the sun, including light reflected from the moon. Predation risk is strongly determined by light conditions, and some animals are nocturnal to reduce predation. Artificial lights and its consequent light pollution may disrupt this natural behavior. Here, we used 13 years of attendance data to study the effects of sun, moon, and artificial light on the attendance pattern of a nocturnal seabird, the little penguin Eudyptula minor at Phillip Island, Australia. The little penguin is the smallest and the only penguin species whose activity on land is strictly nocturnal. Automated monitoring systems recorded individually marked penguins every time they arrived (after sunset) at or departed (before sunrise) from 2 colonies under different lighting conditions: natural night skylight and artificial lights (around 3 lux) used to enhance penguin viewing for ecotourism around sunset. Sunlight had a strong effect on attendance as penguins arrived on average around 81 min after sunset and departed around 92 min before sunrise. The effect of moonlight was also strong, varying according to moon phase. Fewer penguins came ashore during full moon nights. Moon phase effect was stronger on departure than arrival times. Thus, during nights between full moon and last quarter, arrival times (after sunset) were delayed, even though moonlight levels were low, while departure times (before sunrise) were earlier, coinciding with high moonlight levels. Cyclic patterns of moon effect were slightly out of phase but significantly between 2 colonies, which could be due to site-specific differences or presence/absence of artificial lights. Moonlight could be overridden by artificial light at our artificially lit colony, but the similar amplitude of attendance patterns between colonies suggests that artificial light did not mask the moonlight effect. Further research is indeed necessary to understand how seabirds respond to the increasing artificial night light levels. PMID- 26823446 TI - p53 mRNA and p53 Protein Structures Have Evolved Independently to Interact with MDM2. AB - The p53 tumor suppressor and its key regulator MDM2 play essential roles in development, ageing, cancer, and cellular stress responses in mammals. Following DNA damage, MDM2 interacts with p53 mRNA in an ATM kinase-dependent fashion and stimulates p53 synthesis, whereas under normal conditions, MDM2 targets the p53 protein for degradation. The peptide- and RNA motifs that interact with MDM2 are encoded by the same conserved BOX-I sequence, but how these interactions have evolved is unknown. Here, we show that a temperature-sensitive structure in the invertebrate Ciona intestinalis (Ci) p53 mRNA controls its interaction with MDM2. We also show that a nonconserved flanking region of Ci-BOX-I domain prevents the p53-MDM2 protein-protein interaction. These results indicate that the temperature regulated p53 mRNA-MDM2 interaction evolved to become kinase regulated in the mammalian DNA damage response. The data also suggest that the negative regulation of p53 by MDM2 via protein-protein interaction evolved in vertebrates following changes in the BOX-I flanking sequence. PMID- 26823447 TI - Genomic Analyses Reveal Demographic History and Temperate Adaptation of the Newly Discovered Honey Bee Subspecies Apis mellifera sinisxinyuan n. ssp. AB - Studying the genetic signatures of climate-driven selection can produce insights into local adaptation and the potential impacts of climate change on populations. The honey bee (Apis mellifera) is an interesting species to study local adaptation because it originated in tropical/subtropical climatic regions and subsequently spread into temperate regions. However, little is known about the genetic basis of its adaptation to temperate climates. Here, we resequenced the whole genomes of ten individual bees from a newly discovered population in temperate China and downloaded resequenced data from 35 individuals from other populations. We found that the new population is an undescribed subspecies in the M-lineage of A. mellifera (Apis mellifera sinisxinyuan). Analyses of population history show that long-term global temperature has strongly influenced the demographic history of A. m. sinisxinyuan and its divergence from other subspecies. Further analyses comparing temperate and tropical populations identified several candidate genes related to fat body and the Hippo signaling pathway that are potentially involved in adaptation to temperate climates. Our results provide insights into the demographic history of the newly discovered A. m. sinisxinyuan, as well as the genetic basis of adaptation of A. mellifera to temperate climates at the genomic level. These findings will facilitate the selective breeding of A. mellifera to improve the survival of overwintering colonies. PMID- 26823449 TI - Mitral and aortic valve stenosis in alkaptonuria. PMID- 26823448 TI - Spontaneous Reproductive Tract Lesions in Aged Captive Chimpanzees. AB - Chimpanzees (Pan troglodytes) have served as an important model for studies of reproductive diseases and aging-related disorders in humans. However, limited information is available about spontaneously occurring reproductive tract lesions in aging chimpanzees. In this article, the authors present histopathologic descriptions of lesions identified in the reproductive tract, including the mammary gland, of 33 female and 34 male aged chimpanzees from 3 captive populations. The most common findings in female chimpanzees were ovarian atrophy, uterine leiomyoma, adenomyosis, and endometrial atrophy. The most common findings in male chimpanzees were seminiferous tubule degeneration and lymphocytic infiltrates in the prostate gland. Other less common lesions included an ovarian granulosa cell tumor, cystic endometrial hyperplasia, an endometrial polyp, uterine artery hypertrophy and mineralization, atrophic vaginitis, mammary gland inflammation, prostatic epithelial hyperplasia, dilated seminal vesicles, a sperm granuloma, and lymphocytic infiltrates in the epididymis. The findings in this study closely mimic changes described in the reproductive tract of aged humans, with the exception of a lack of malignant changes observed in the mammary gland and prostate gland. PMID- 26823450 TI - Isolated left pectoralis major muscle hypoplasia in Poland syndrome. PMID- 26823451 TI - Does Superficial Medial Collateral Ligament Release in Open-Wedge High Tibial Osteotomy for Varus Osteoarthritic Knees Increase Valgus Laxity? AB - BACKGROUND: Medial open-wedge high tibial osteotomy (OWHTO) requires the release of the superficial medial collateral ligament (sMCL). However, research on medial laxity among patients who undergo OWHTO is rare. PURPOSE: To evaluate the changes in medial laxity of the knee joint as related to the complete release of the sMCL through serial valgus stress radiographs in patients who underwent OWHTO. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 48 patients (54 knees) who received OWHTO and were followed for more than a year and for whom serial valgus stress radiography data were available were retrospectively reviewed. To assess the medial laxity of knee joint, medial joint space opening (MJO) was measured while valgus stress of 15 kgf was loaded on the knee joint. The MJO was measured before surgery, during surgery before release of the sMCL under anesthesia, after the release, and after fixing with a TomoFix plate following the opening of the osteotomy site, as well as 3, 6, and 12 months after surgery. Serially measured MJOs were analyzed to evaluate the changes of medial laxity. RESULTS: The MJO significantly increased after the release of the sMCL (mean +/- SD, 12.2 +/- 1.2 mm) compared with before the release (9.0 +/- 1.1 mm) (P < .001). The MJO measured after fixing with the TomoFix plate following the opening of the osteotomy site (9.2 +/- 1.2 mm) was significantly decreased compared with that measured after the release of the sMCL and was not significantly different from the MJO measured before release of the sMCL. No significant difference was observed among MJOs that were measured 3, 6, and 12 months after surgery. Comparison of MJOs before and after surgery also showed no significant differences. CONCLUSION: Complete release of the sMCL during OWHTO increases the MJO. However, the MJO decreased to the level before sMCL release after fixing with the TomoFix plate following the opening of the osteotomy site. Medial laxity induced by the complete release of the sMCL can be recovered by opening the osteotomy site. PMID- 26823452 TI - Prevalence of Cam-Type Morphology in Elite Ice Hockey Players. AB - BACKGROUND: Femoroacetabular impingement (FAI) has been increasingly recognized as a cause of hip pain in athletes at all levels of competition, specifically ice hockey players. PURPOSE/HYPOTHESIS: The purpose of this study was to define the prevalence of cam and pincer radiographic deformity in elite ice hockey players. The hypothesis was that elite hockey players will have a higher prevalence of radiographic hip abnormalities compared with the general population. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Anteroposterior and frog-leg lateral radiographs on 137 elite ice hockey players were prospectively obtained during the 2014-2015 preseason entrance examinations. Study participants included National Hockey League roster players as well as the respective farm team members. Demographic data were collected, including age, position, shooting side, and any history of hip pain or hip surgery. Patients with a history of hip surgery were excluded from the analysis. A single sports medicine fellowship trained orthopaedic surgeon used standard radiographic measurements to assess for the radiographic presence of cam or pincer deformity. Radiographs with an alpha angle >=55 degrees on a frog-leg lateral view were defined as cam-positive. Each participant underwent a preseason physical examination with an assessment of hip range of motion and impingement testing. RESULTS: A total of 130 elite ice hockey players were included in the analysis; 180 (69.4%) hips met radiographic criteria for cam-type deformity. The prevalence in right and left hips was 89 (69.5%) and 91 (70.0%), respectively; 70 (60.8%) players demonstrated bilateral involvement. Hips with cam deformity had a mean alpha angle of 67.7 degrees +/- 8.3 degrees on the right and 68.9 degrees +/- 9.0 degrees on the left. Of the patients with alpha angles >=55 degrees , 5.6% (5/89) had a positive anterior impingement test of the right hip, while 11% (10/91) had positive anterior impingement test of the left. Players with radiologic cam deformity had a statistically significant deficit in external rotation of the right hip, as well as in both internal and external rotation of the left hip, compared with those with normal alpha angles. When assessing for crossover sign, 64 of 107 (59.8%) had a positive radiographic finding. Forty-one players (38.3%) had evidence of a crossover sign of the right hip and 42 (39.3%) of the left. When comparing position players, goalies had the highest prevalence of cam-type deformity (93.8%) and the least acetabular coverage. CONCLUSION: The study data suggest that elite ice hockey players have a significantly higher prevalence of radiographic cam deformity in comparison to what has been reported for the general population. PMID- 26823453 TI - Getting from A to B-exploring the activation motifs of the class B adhesion G protein-coupled receptor subfamily G member 4/GPR112. AB - The adhesion G protein-coupled receptors [ADGRs/class B2 G protein-coupled receptors (GPCRs)] constitute an ancient family of GPCRs that have recently been demonstrated to play important roles in cellular and developmental processes. Here, we describe a first insight into the structure-function relationship of ADGRs using the family member ADGR subfamily G member 4 (ADGRG4)/GPR112 as a model receptor. In a bioinformatics approach, we compared conserved, functional elements of the well-characterized class A and class B1 secretin-like GPCRs with the ADGRs. We identified several potential equivalent motifs and subjected those to mutational analysis. The importance of the mutated residues was evaluated by examining their effect on the high constitutive activity of the N-terminally truncated ADGRG4/GPR112 in a 1-receptor-1-G protein Saccharomyces cerevisiae screening system and was further confirmed in a transfected mammalian human embryonic kidney 293 cell line. We evaluated the results in light of the crystal structures of the class A adenosine A2A receptor and the class B1 corticotropin releasing factor receptor 1. ADGRG4 proved to have functionally important motifs resembling class A, class B, and combined elements, but also a unique highly conserved ADGR motif (H3.33). Given the high conservation of these motifs and residues across the adhesion GPCR family, it can be assumed that these are general elements of ADGR function.-Peeters, M. C., Mos, I., Lenselink, E. B., Lucchesi, M., IJzerman, A. P., Schwartz, T. W. Getting from A to B-exploring the activation motifs of the class B adhesion G protein-coupled receptor subfamily G member 4/GPR112. PMID- 26823455 TI - Ferromagnetic properties in low-doped zigzag graphene nanoribbons. AB - The temperature-dependent edge magnetic susceptibility [Formula: see text] and the uniform magnetic susceptibility chi in zigzag graphene nanoribbons is studied within the Hubbard model on a honeycomb lattice. By using the determinant quantum Monte Carlo (DQMC) method, it is found that the ferromagnetic fluctuations at the zigzag edge dominate around half-filling, and that the fluctuations are strengthened markedly by the on-site Coulomb interaction U, which may lead to a possible high-temperature edge ferromagnetic behaviour in low-doped zigzag graphene nanoribbons. PMID- 26823454 TI - Lung ICAM-1 and ICAM-2 support spontaneous intravascular effector lymphocyte entrapment but are not required for neutrophil entrapment or emigration inside endotoxin-inflamed lungs. AB - The pulmonary vasculature constitutively expresses the integrin lymphocyte function-associated antigen-1 ligands intercellular adhesion molecule (ICAM)-1 and -2. In this study, effector T cells were temporarily entrapped by the lung vasculature on their way to inflamed lymph nodes, and this entrapment was strongly reduced in ICAM-1 and -2 double-deficient mice (79 and 86% reduction for CD8(+) and CD4(+) effectors, respectively, compared with wild-type mice). Although the pulmonary vasculature has been suggested to be masked by the heparan sulfate-containing glycocalyx, which is susceptible to heparanase-mediated shedding, lung and lymphocyte heparanase have been found to be unnecessary for this entrapment. Systemic LPS induced rapid neutrophil entrapment in the lung vasculature, but in contrast to T-cell entrapment, this sequestration was ICAM-1, ICAM-2, and heparanase independent. Furthermore, neutrophil migration into the bronchoalveolar space induced by LPS inhalation and LPS-induced leakage of red blood cells into this space were not dependent on lung ICAMs or heparanase activity. Nevertheless, heparanase was critical for neutrophil accumulation in smoke-exposed lungs. Our results indicate that, whereas T cells use ICAM-1 and -2 for temporary pulmonary entrapment, neutrophils get sequestered and extravasate into inflamed lungs independent of ICAMs. This is the first demonstration that the pulmonary vasculature is differentially recognized by T cells and neutrophils.-Petrovich, E., Feigelson, S. W., Stoler-Barak, L., Hatzav, M., Solomon, A., Bar-Shai, A., Ilan, N., Li, J.-P., Engelhardt, B., Vlodavsky, I., Alon, R. Lung ICAM-1 and ICAM-2 support spontaneous intravascular effector lymphocyte entrapment but are not required for neutrophil entrapment or emigration inside endotoxin-inflamed lungs. PMID- 26823456 TI - Antithrombotic therapy in peripheral artery disease. AB - Antiplatelet agents are recommended for the reduction of major adverse cardiovascular events among all patients with symptomatic peripheral artery disease. However, the optimal antiplatelet regimen and duration of therapy in peripheral artery disease (PAD) remains unclear, largely due to limited and conflicting data in this patient population. This article reviews current data on antithrombotic therapy in PAD and discusses the implications of this data for current practice and future research. PMID- 26823457 TI - Using three-dimensional isotropic SPACE MRI to detect posterolateral corner injury of the knee. AB - BACKGROUND: Reliable magnetic resonance imaging (MRI) diagnosis is important in cases of posterolateral corner (PLC) injury due to the limitations of physical examination in patients with multi-ligament injury. PURPOSE: To document the appearance of PLC of the knee on three-dimensional (3D) isotropic MR images, and to determine the significance of MRI findings in patients with confirmed posterolateral rotatory instability. MATERIAL AND METHODS: Twenty-five patients that underwent surgery for posterolateral instability, and 25 individuals with normal MRI constituted the study cohort. The PLC appearances (popliteofibular, fabellofibular, arcuate ligaments, popliteomeniscal fascicle) were analyzed using 3D isotropic proton density sequence and routine two-dimensional (2D) MRI. In addition, the "fibular cap" sign was evaluated. Statistical analysis was performed using the Chi-square and McNemar's tests. RESULTS: Thickening of popliteofibular, fabellofibular, arcuate ligaments, and popliteomeniscal fascicle was significantly more frequent in the PLC injury group than in the control group (P < 0.05). The sensitivity and specificity of 3D MRI for popliteofibular, fabellofibular, arcuate ligaments, and popliteomeniscal fascicle injury were 63/92%, 54/100%, 46/100%, and 58/92%, respectively. On comparing 3D and 2D images with respect to injury detectability (grade 3 or 4), both modalities visualized injuries, but 3D detected grade 3 or grade 1 rather than grade 4 or 0, respectively. The fibular cap sign was observed significantly more frequently in PLC group, with 58% sensitivity and 100% specificity, and was better observed by 3D than 2D (P < 0.05). CONCLUSION: 3D MRI is a valid modality for detecting PLC abnormalities as it visualizes pathologies in each component and exhibits the positive fibular cap sign. PMID- 26823458 TI - Mossbauer spectroscopy, magnetization, magnetic susceptibility, and low temperature heat capacity of alpha-Na2NpO4. AB - The physical and chemical properties at low temperatures of hexavalent disodium neptunate alpha-Na2NpO4 are investigated for the first time in this work using Mossbauer spectroscopy, magnetization, magnetic susceptibility, and heat capacity measurements. The Np(VI) valence state is confirmed by the isomer shift value of the Mossbauer spectra, and the local structural environment around the neptunium cation is related to the fitted quadrupole coupling constant and asymmetry parameters. Moreover, magnetic hyperfine splitting is reported below 12.5 K, which could indicate magnetic ordering at this temperature. This interpretation is further substantiated by the existence of a lambda-peak at 12.5 K in the heat capacity curve, which is shifted to lower temperatures with the application of a magnetic field, suggesting antiferromagnetic ordering. However, the absence of any anomaly in the magnetization and magnetic susceptibility data shows that the observed transition is more intricate. In addition, the heat capacity measurements suggest the existence of a Schottky-type anomaly above 15 K associated with a low-lying electronic doublet found about 60 cm(-1) above the ground state doublet. The possibility of a quadrupolar transition associated with a ground state pseudoquartet is thereafter discussed. The present results finally bring new insights into the complex magnetic and electronic peculiarities of alpha-Na2NpO4. PMID- 26823459 TI - Antisite disorder driven spontaneous exchange bias effect in La(2-x)Sr(x) CoMnO6 (0 ? x ? 1). AB - Doping at the rare-earth site by divalent alkaline-earth ions in perovskite lattice has witnessed a variety of magnetic and electronic orders with spatially correlated charge, spin and orbital degrees of freedom. Here, we report an antisite disorder driven spontaneous exchange bias effect as a result of hole carrier (Sr(2+)) doping in La(2-x)Sr(x)CoMnO6 (0 < x < 1) double perovskites. X-ray diffraction and Raman spectroscopy have evidenced an increase in disorder with the increase of Sr content up to x = 0.5 and thereby a decrease from x = 0.5 to 1. X-ray absorption spectroscopy has revealed that only Co is present in the mixed valence of Co(2+) and Co(3+) states with Sr doping to compensate the charge neutrality. Magnetotransport is strongly correlated with the increase of antisite disorder. The antisite disorder at the B-site interrupts the long-range ferromagnetic order by introducing various magnetic interactions and instigates reentrant glassy dynamics, phase separation and canted type antiferromagnetic behavior with the decrease of temperature. This leads to a novel magnetic microstructure with unidirectional anisotropy that causes a spontaneous exchange bias effect that can be tuned with the amount of antisite disorder. PMID- 26823460 TI - Binding of Hyaluronan to the Native Lymphatic Vessel Endothelial Receptor LYVE-1 Is Critically Dependent on Receptor Clustering and Hyaluronan Organization. AB - The lymphatic endothelial receptor LYVE-1 has been implicated in both uptake of hyaluronan (HA) from tissue matrix and in facilitating transit of leukocytes and tumor cells through lymphatic vessels based largely onin vitrostudies with recombinant receptor in transfected fibroblasts. Curiously, however, LYVE-1 in lymphatic endothelium displays little if any binding to HAin vitro, and this has led to the conclusion that the native receptor is functionally silenced, a feature that is difficult to reconcile with its proposedin vivofunctions. Nonetheless, as we reported recently, LYVE-1 can function as a receptor for HA encapsulated Group A streptococci and mediate lymphatic dissemination in mice. Here we resolve these paradoxical findings and show that the capacity of LYVE-1 to bind HA is strictly dependent on avidity, demanding appropriate receptor self association and/or HA multimerization. In particular, we demonstrate the prerequisite of a critical LYVE-1 threshold density and show that HA binding may be elicited in lymphatic endothelium by surface clustering with divalent LYVE-1 mAbs. In addition, we show that cross-linking of biotinylated HA in streptavidin multimers or supramolecular complexes with the inflammation-induced protein TSG-6 enables binding even in the absence of LYVE-1 cross-linking. Finally, we show that endogenous HA on the surface of macrophages can engage LYVE-1, facilitating their adhesion and transit across lymphatic endothelium. These results reveal LYVE-1 as a low affinity receptor tuned to discriminate between different HA configurations through avidity and establish a new mechanistic basis for the functions ascribed to LYVE-1 in matrix HA binding and leukocyte traffickingin vivo. PMID- 26823461 TI - SLO2 Channels Are Inhibited by All Divalent Cations That Activate SLO1 K+ Channels. AB - Two members of the family of high conductance K(+)channels SLO1 and SLO2 are both activated by intracellular cations. However, SLO1 is activated by Ca(2+)and other divalent cations, while SLO2 (Slack or SLO2.2 from rat) is activated by Na(+) Curiously though, we found that SLO2.2 is inhibited by all divalent cations that activate SLO1, with Zn(2+)being the most effective inhibitor with an IC50of ~8 MUmin contrast to Mg(2+), the least effective, with an IC50of ~ 1.5 mm Our results suggest that divalent cations are not SLO2 pore blockers, but rather inhibit channel activity by an allosteric modification of channel gating. By site directed mutagenesis we show that a histidine residue (His-347) downstream of S6 reduces inhibition by divalent cations. An analogous His residue present in some CNG channels is an inhibitory cation binding site. To investigate whether inhibition by divalent cations is conserved in an invertebrate SLO2 channel we cloned the SLO2 channel fromDrosophila(dSLO2) and compared its properties to those of rat SLO2.2. We found that, like rat SLO2.2, dSLO2 was also activated by Na(+)and inhibited by divalent cations. Inhibition of SLO2 channels in mammals andDrosophilaby divalent cations that have second messenger functions may reflect the physiological regulation of these channels by one or more of these ions. PMID- 26823462 TI - A Method for Multiplexed Measurement of Mitochondrial Pyruvate Carrier Activity. AB - The discovery that theMPC1andMPC2genes encode the protein components of the mitochondrial pyruvate carrier (MPC) has invigorated studies of mitochondrial pyruvate transport and its regulation in normal and disease states. Indeed, recent reports have demonstrated MPC involvement in the control of cell fate in cancer and gluconeogenesis in models of type 2 diabetes. Biochemical measurements of MPC activity are foundational for understanding the role of pyruvate transport in health and disease. We developed a 96-well scaled method of [(14)C]pyruvate uptake that markedly decreases sample requirements and increases throughput relative to previous techniques. This method was applied to determine the mouse liver MPCKm(28.0 +/- 3.9 MUm) andVmax(1.08 +/- 0.05 nmol/min/mg), which have not previously been reported.KmandVmaxof the rat liver MPC were found to be 71.2 +/- 17 MUmand 1.42 +/- 0.14 nmol/min/mg, respectively. Additionally, we performed parallel pyruvate uptake and oxidation experiments with the same biological samples and show differential results in response to fasting, demonstrating the continued importance of a direct MPC activity assay. We expect this method will be of value for understanding the contribution of the MPC activity to health and disease states where pyruvate metabolism is expected to play a prominent role. PMID- 26823463 TI - Structural Analysis of beta-Fructofuranosidase from Xanthophyllomyces dendrorhous Reveals Unique Features and the Crucial Role of N-Glycosylation in Oligomerization and Activity. AB - Xanthophyllomyces dendrorhousbeta-fructofuranosidase (XdINV)is a highly glycosylated dimeric enzyme that hydrolyzes sucrose and releases fructose from various fructooligosaccharides (FOS) and fructans. It also catalyzes the synthesis of FOS, prebiotics that stimulate the growth of beneficial bacteria in human gut. In contrast to most fructosylating enzymes, XdINV produces neo-FOS, which makes it an interesting biotechnology target. We present here its three dimensional structure, which shows the expected bimodular arrangement and also a long extension of its C terminus that together with anN-linked glycan mediate the formation of an unusual dimer. The two active sites of the dimer are connected by a long crevice, which might indicate its potential ability to accommodate branched fructans. This arrangement could be representative of a group of GH32 yeast enzymes having the traits observed in XdINV. The inactive D80A mutant was used to obtain complexes with relevant substrates and products, with their crystals structures showing at least four binding subsites at each active site. Moreover, two different positions are observed from subsite +2 depending on the substrate, and thus, a flexible loop (Glu-334-His-343) is essential in binding sucrose and beta(2-1)-linked oligosaccharides. Conversely, beta(2-6) and neo-type substrates are accommodated mainly by stacking to Trp-105, explaining the production of neokestose and the efficient fructosylating activity of XdINV on alpha-glucosides. The role of relevant residues has been investigated by mutagenesis and kinetics measurements, and a model for the transfructosylating reaction has been proposed. The plasticity of its active site makes XdINV a valuable and flexible biocatalyst to produce novel bioconjugates. PMID- 26823464 TI - Multiple Plasmodium falciparum Merozoite Surface Protein 1 Complexes Mediate Merozoite Binding to Human Erythrocytes. AB - Successful invasion of human erythrocytes byPlasmodium falciparummerozoites is required for infection of the host and parasite survival. The early stages of invasion are mediated via merozoite surface proteins that interact with human erythrocytes. The nature of these interactions are currently not well understood, but it is known that merozoite surface protein 1 (MSP1) is critical for successful erythrocyte invasion. Here we show that the peripheral merozoite surface proteins MSP3, MSP6, MSPDBL1, MSPDBL2, and MSP7 bind directly to MSP1, but independently of each other, to form multiple forms of the MSP1 complex on the parasite surface. These complexes have overlapping functions that interact directly with human erythrocytes. We also show that targeting the p83 fragment of MSP1 using inhibitory antibodies inhibits all forms of MSP1 complexes and disrupts parasite growthin vitro. PMID- 26823465 TI - Identification of the Allosteric Site for Phenylalanine in Rat Phenylalanine Hydroxylase. AB - Liver phenylalanine hydroxylase (PheH) is an allosteric enzyme that requires activation by phenylalanine for full activity. The location of the allosteric site for phenylalanine has not been established. NMR spectroscopy of the isolated regulatory domain (RDPheH(25-117) is the regulatory domain of PheH lacking residues 1-24) of the rat enzyme in the presence of phenylalanine is consistent with formation of a side-by-side ACT dimer. Six residues in RDPheH(25-117) were identified as being in the phenylalanine-binding site on the basis of intermolecular NOEs between unlabeled phenylalanine and isotopically labeled protein. The location of these residues is consistent with two allosteric sites per dimer, with each site containing residues from both monomers. Site-specific variants of five of the residues (E44Q, A47G, L48V, L62V, and H64N) decreased the affinity of RDPheH(25-117) for phenylalanine based on the ability to stabilize the dimer. Incorporation of the A47G, L48V, and H64N mutations into the intact protein increased the concentration of phenylalanine required for activation. The results identify the location of the allosteric site as the interface of the regulatory domain dimer formed in activated PheH. PMID- 26823466 TI - RipAY, a Plant Pathogen Effector Protein, Exhibits Robust gamma-Glutamyl Cyclotransferase Activity When Stimulated by Eukaryotic Thioredoxins. AB - The plant pathogenic bacterium Ralstonia solanacearum injects more than 70 effector proteins (virulence factors) into the host plant cells via the needle like structure of a type III secretion system. The type III secretion system effector proteins manipulate host regulatory networks to suppress defense responses with diverse molecular activities. Uncovering the molecular function of these effectors is essential for a mechanistic understanding of R. solanacearum pathogenicity. However, few of the effectors from R. solanacearum have been functionally characterized, and their plant targets remain largely unknown. Here, we show that the ChaC domain-containing effector RipAY/RSp1022 from R. solanacearum exhibits gamma-glutamyl cyclotransferase (GGCT) activity to degrade the major intracellular redox buffer, glutathione. Heterologous expression of RipAY, but not other ChaC family proteins conserved in various organisms, caused growth inhibition of yeast Saccharomyces cerevisiae, and the intracellular glutathione level was decreased to ~30% of the normal level following expression of RipAY in yeast. Although active site mutants of GGCT activity were non-toxic, the addition of glutathione did not reverse the toxicity, suggesting that the toxicity might be a consequence of activity against other gamma-glutamyl compounds. Intriguingly, RipAY protein purified from a bacterial expression system did not exhibit any GGCT activity, whereas it exhibited robust GGCT activity upon its interaction with eukaryotic thioredoxins, which are important for intracellular redox homeostasis during bacterial infection in plants. Our results suggest that RipAY has evolved to sense the host intracellular redox environment, which triggers its enzymatic activity to create a favorable environment for R. solanacearum infection. PMID- 26823467 TI - Dual Oxidase 2 (Duox2) Regulates Pannexin 1-mediated ATP Release in Primary Human Airway Epithelial Cells via Changes in Intracellular pH and Not H2O2 Production. AB - Human airway epithelial cells express pannexin 1 (Panx1) channels to release ATP, which regulates mucociliary clearance. Airway inflammation causes mucociliary dysfunction. Exposure of primary human airway epithelial cell cultures to IFN gamma for 48 h did not alter Panx1 protein expression but significantly decreased ATP release in response to hypotonic stress. The IFN-gamma-induced functional down-regulation of Panx1 was due to the up-regulation of dual oxidase 2 (Duox2). Duox2 suppression by siRNA led to an increase in ATP release in control cells and restoration of ATP release in cells treated with IFN-gamma. Both effects were reduced by the pannexin inhibitor probenecid. Duox2 up-regulation stoichiometrically increases H2O2 and proton production. H2O2 inhibited Panx1 function temporarily by formation of disulfide bonds at the thiol group of its terminal cysteine. Long-term exposure to H2O2, however, had no inhibitory effect. To assess the role of cellular acidification upon IFN-gamma treatment, fully differentiated airway epithelial cells were exposed to ammonium chloride to alkalinize the cytosol. This led to a 2-fold increase in ATP release in cells treated with IFN-gamma that was also inhibited by probenecid. Duox2 knockdown also partially corrected IFN-gamma-mediated acidification. The direct correlation between intracellular pH and Panx1 open probability was shown in oocytes. Therefore, airway epithelial cells release less ATP in response to hypotonic stress in an inflammatory environment (IFN-gamma exposure). Decreased Panx1 function is a response to cell acidification mediated by IFN-gamma-induced up regulation of Duox2, representing a novel mechanism for mucociliary dysfunction in inflammatory airway diseases. PMID- 26823469 TI - Normalised time-to-peak-distribution curves correlate with cerebral white matter hyperintensities - Could this improve early diagnosis? AB - Parameter-free assessment of the time-to-peak (TTP) histogram, termed 'TTP distribution curve' (TDC), of dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) was introduced as a robust method to evaluate cerebral perfusion. TDC-assessment works fully automatically without the need of an arterial input function, thereby providing full comparability between different measurements. In the investigated sample of 106 patients, a strong dependency of TDC on the hemodynamic state of cerebral microvessels and the arterio-venous bolus-transit time [Formula: see text] was demonstrated. Accordingly, TDC-derived [Formula: see text] was 3.3-3.7 s for control patients and 4.4 s for cerebral small vessel disease patients. Measurements of associated bolus spread velocities nu and accelerations [Formula: see text] additionally revealed a direct effect from spin-spin relaxation time T2-weighted white matter hyperintensity volume, considered to indicate microangiopathy in cerebral small vessel disease, on the TDC-measurements. This strongly supports the prevailing hypothesis that cerebral small vessel disease directly influences DSC measurements, where the degree could be estimated from an analysis of TDC. While this may be used to correct DSC-parameters for undesirable effects from cerebral small vessel disease, it could also serve to potentially identify patients at risk for cerebral small vessel disease at an early stage, since a subset of patients without yet significant WHM-volume, but clearly altered hemodynamics in TDC-measurements, was identified in this study. PMID- 26823468 TI - Glutathionylation of the Bacterial Hsp70 Chaperone DnaK Provides a Link between Oxidative Stress and the Heat Shock Response. AB - DnaK is the major bacterial Hsp70, participating in DNA replication, protein folding, and the stress response. DnaK cooperates with the Hsp40 co-chaperone DnaJ and the nucleotide exchange factor GrpE. Under non-stress conditions, DnaK binds to the heat shock transcription factor sigma(32)and facilitates its degradation. Oxidative stress results in temporary inactivation of DnaK due to depletion of cellular ATP and thiol modifications such as glutathionylation until normal cellular ATP levels and a reducing environment are restored. However, the biological significance of DnaK glutathionylation remains unknown, and the mechanisms by which glutathionylation may regulate the activity of DnaK are also unclear. We investigated the conditions under which Escherichia coli DnaK undergoesS-glutathionylation. We observed glutathionylation of DnaK in lysates of E. coli cells that had been subjected to oxidative stress. We also obtained homogeneously glutathionylated DnaK using purified DnaK in the apo state. We found that glutathionylation of DnaK reversibly changes the secondary structure and tertiary conformation, leading to reduced nucleotide and peptide binding ability. The chaperone activity of DnaK was reversibly down-regulated by glutathionylation, accompanying the structural changes. We found that interaction of DnaK with DnaJ, GrpE, or sigma(32)becomes weaker when DnaK is glutathionylated, and the interaction is restored upon deglutathionylation. This study confirms that glutathionylation down-regulates the functions of DnaK under oxidizing conditions, and this down-regulation may facilitate release of sigma(32)from its interaction with DnaK, thus triggering the heat shock response. Such a mechanism provides a link between oxidative stress and the heat shock response in bacteria. PMID- 26823470 TI - Aging alters the dampening of pulsatile blood flow in cerebral arteries. AB - Excessive pulsatile flow caused by aortic stiffness is thought to be a contributing factor for several cerebrovascular diseases. The main purpose of this study was to describe the dampening of the pulsatile flow from the proximal to the distal cerebral arteries, the effect of aging and sex, and its correlation to aortic stiffness. Forty-five healthy elderly (mean age 71 years) and 49 healthy young (mean age 25 years) were included. Phase-contrast magnetic resonance imaging was used for measuring blood flow pulsatility index and dampening factor (proximal artery pulsatility index/distal artery pulsatility index) in 21 cerebral and extra-cerebral arteries. Aortic stiffness was measured as aortic pulse wave velocity. Cerebral arterial pulsatility index increased due to aging and this was more pronounced in distal segments of cerebral arteries. There was no difference in pulsatility index between women and men. Dampening of pulsatility index was observed in all cerebral arteries in both age groups but was significantly higher in young subjects than in elderly. Pulse wave velocity was not correlated with cerebral arterial pulsatility index. The increased pulsatile flow in elderly together with reduced dampening supports the pulse wave encephalopathy theory, since it implies that a higher pulsatile flow is reaching distal arterial segments in older subjects. PMID- 26823472 TI - Compartmentalised energy metabolism supporting glutamatergic neurotransmission in response to increased activity in the rat cerebral cortex: A 13C MRS study in vivo at 14.1 T. AB - Many tissues exhibit metabolic compartmentation. In the brain, while there is no doubt on the importance of functional compartmentation between neurons and glial cells, there is still debate on the specific regulation of pathways of energy metabolism at different activity levels. Using (13)C magnetic resonance spectroscopy (MRS) in vivo, we determined fluxes of energy metabolism in the rat cortex under alpha-chloralose anaesthesia at rest and during electrical stimulation of the paws. Compared to resting metabolism, the stimulated rat cortex exhibited increased glutamate-glutamine cycle (+67 nmol/g/min, +95%, P < 0.001) and tricarboxylic (TCA) cycle rate in both neurons (+62 nmol/g/min, +12%, P < 0.001) and astrocytes (+68 nmol/g/min, +22%, P = 0.072). A minor, non significant modification of the flux through pyruvate carboxylase was observed during stimulation (+5 nmol/g/min, +8%). Altogether, this increase in metabolism amounted to a 15% (67 nmol/g/min, P < 0.001) increase in CMRglc(ox), i.e. the oxidative fraction of the cerebral metabolic rate of glucose. In conclusion, stimulation of the glutamate-glutamine cycle under alpha-chloralose anaesthesia is associated to similar enhancement of neuronal and glial oxidative metabolism. PMID- 26823471 TI - The blood-brain barrier after stroke: Structural studies and the role of transcytotic vesicles. AB - Blood-brain barrier breakdown worsens ischaemic damage, but it is unclear how molecules breach the blood-brain barrier in vivo. Using the obese ob/ob mouse as a model of enhanced blood-brain barrier breakdown, we investigated how stroke induced structural changes to the microvasculature related to blood-brain barrier permeability. Ob/ob mice underwent middle cerebral artery occlusion, followed by 4 or 24 h reperfusion. Blood-brain barrier integrity was assessed using IgG and horseradish peroxidase staining, and blood-brain barrier structure by two dimensional and three-dimensional electron microscopy. At 4 and 24 h post-stroke, ob/ob mice had increased ischaemic damage and blood-brain barrier breakdown compared to ob/- controls, and vessels from both genotypes showed astrocyte end foot swelling and increased endothelial vesicles. Ob/ob mice had significantly more endothelial vesicles at 4 h in the striatum, where blood-brain barrier breakdown was most severe. Both stroke and genotype had no effect on tight junction structure visualised by electron microscopy, or protein expression in isolated microvessels. Astrocyte swelling severity did not correlate with tissue outcome, being unaffected by genotype or reperfusion times. However, the rare instances of vessel lumen collapse were always associated with severe astrocyte swelling in two-dimensional and three-dimensional electron microscopy. Endothelial vesicles were therefore the best spatial and temporal indicators of blood-brain barrier breakdown after cerebral ischaemia. PMID- 26823473 TI - Pulse pressure-dependent cerebrovascular eNOS regulation in mice. AB - Arterial blood pressure is oscillatory; whether pulse pressure (PP) regulates cerebral artery myogenic tone (MT) and endothelial function is currently unknown. To test the impact of PP on MT and dilation to flow (FMD) or to acetylcholine (Ach), isolated pressurized mouse posterior cerebral arteries were subjected to either static pressure (SP) or a physiological PP (amplitude: 30 mm Hg; frequency: 550 bpm). Under PP, MT was significantly higher than in SP conditions ( p < 0.05) and was not affected by eNOS inhibition. In contrast, under SP, eNOS inhibition increased ( p < 0.05) MT to levels observed under PP, suggesting that PP may inhibit eNOS. At a shear stress of 20 dyn/cm2, FMD was lower ( p < 0.05) under SP than PP. Under SP, eNOS-dependent [Formula: see text] production contributed to FMD, while under PP, eNOS-dependent NO was responsible for FMD, indicating that PP favours eNOS coupling. Differences in FMD between pressure conditions were abolished after NOX2 inhibition. In contrast to FMD, Ach-induced dilations were higher ( p < 0.05) under SP than PP. Reactive oxygen species scavenging reduced ( p < 0.05) Ach-dependent dilations under SP, but increased ( p < 0.05) them under PP; hence, under PP, Ach promotes ROS production and limits eNOS-derived NO activity. In conclusion, PP finely regulates eNOS, controlling cerebral artery reactivity. PMID- 26823474 TI - Cerebrospinal fluid high mobility group box 1 is associated with neuronal death in subarachnoid hemorrhage. AB - We aim to determine the cerebrospinal fluid levels of high mobility group box 1 in subarachnoid hemorrhage patients and to investigate the involvement of the receptor for advanced glycation end products and high mobility group box 1 in the pathogenesis of post-subarachnoid hemorrhage neuronal death. The study included 40 patients (mean age, 59 +/- 19 years) with Fisher's grade >= III aneurysmal subarachnoid hemorrhage. Cerebrospinal fluid was collected on the seventh day post-hemorrhage. Receptor for advanced glycation end products expression was examined in rat brain tissue following subarachnoid hemorrhage and in cultured neurons exposed to post-subarachnoid hemorrhage cerebrospinal fluid. Therapeutic effects of the recombinant soluble form of RAGE on subarachnoid hemorrhage models were also investigated. The results indicated that a higher level of cerebrospinal fluid high mobility group box 1 was independently associated with unfavorable outcome at three months post-subarachnoid hemorrhage (OR = 1.061, 95% CI: 1.005-1.121). Expression of RAGE increased in post-subarachnoid hemorrhage rat brain cells and in cultured neuron with stimulation of post-subarachnoid hemorrhage cerebrospinal fluid. Administration of recombinant soluble form of RAGE significantly reduced the number of positive TUNEL staining cells in subarachnoid hemorrhage rat and improved cell viability in post-subarachnoid hemorrhage cerebrospinal fluid-treated cultured neurons. Thus, the level of cerebrospinal fluid high mobility group box 1 can be a prognostic indicator for patients with Fisher's grade >= III aneurysmal subarachnoid hemorrhage and that treatment with soluble form of RAGE is a novel approach for subarachnoid hemorrhage. PMID- 26823476 TI - Birth Size Characteristics and Risk of Brain Tumors in Early Adulthood: Results from a Swedish Cohort Study. AB - BACKGROUND: Despite extensive research on the effect of birth size characteristics on childhood brain tumors, very few studies have evaluated the effect of birth size characteristics on the risk of adult brain tumor, and they have provided inconsistent results. METHODS: All individuals born in Sweden between 1973 and 1995 who were still alive and cancer free at their 15th birthday were included in the study (n = 2,032,727). At the end of the study period (December 31, 2010), the study participants were 15 to 37 years old. Incident cases of primary brain tumors were identified through the Swedish Cancer Register. RESULTS: No association was observed between any birth size characteristics and glioma, although an indication of increased glioma risk associated with high birth weight, or being large for gestational age at birth, was found among men [relative risk (RR) = 1.36, 95% confidence interval (CI), 0.97-1.90; RR = 1.44, 95% CI, 0.99-2.09, respectively]. An increased risk of meningioma was observed among individuals born with a large head circumference (RR = 1.76, 95% CI, 1.01-3.05). Large head circumference was also associated with an elevated risk of neuroma (RR = 1.86, 95% CI, 0.94-3.68). Being born small for gestational age was also related to a higher risk of neuroma (RR = 2.50, 95% CI, 1.31-4.78). CONCLUSION: Selected birth size characteristics were associated with increased risk of some brain tumor subtypes in young adults. IMPACT: We have presented additional evidence suggesting that birth size characteristics are associated with subsequent primary brain tumor risk in young adults. Cancer Epidemiol Biomarkers Prev; 25(4); 678-85. (c)2016 AACR. PMID- 26823477 TI - Heme Iron Intake, Dietary Antioxidant Capacity, and Risk of Colorectal Adenomas in a Large Cohort Study of French Women. AB - BACKGROUND: Nitrosylated and non-nitrosylated heme iron from red processed and nonprocessed meat have been associated with increased colorectal carcinogenesis. Mechanisms include oxidative processes. It has been hypothesized that dietary antioxidants could counteract the effects of heme iron. We investigated the relationships between heme iron intake and the risk of colorectal adenomas, and a potential interaction with the dietary antioxidant capacity, in the E3N prospective cohort study. METHODS: The study included 17,397 women, who underwent at least one colonoscopy. Among them, 1,409 were diagnosed with at least one first colorectal adenoma during the 103,253 person-years of follow-up. Dietary intake was measured by a semiquantitative food history questionnaire. HR estimates and 95% confidence intervals (CI) were obtained from Cox proportional hazards models, adjusted for potential confounders. RESULTS: Heme iron intake was positively associated with colorectal and colon adenoma risks [HR for the fourth vs. first quartile: HR4 = 1.36 (1.13-1.65), Ptrend = 0.001 and HR4 = 1.49; 95% CI, 1.19-1.87; Ptrend = 0.0003, respectively]. Nonnitrosylated and nitrosylated heme iron intakes were, respectively, associated with advanced distal and proximal adenoma risks. There was a dose-effect relationship between the heme iron to total dietary antioxidant capacity ratio and colorectal adenoma risk. CONCLUSION: In this prospective cohort study, the association between heme iron and colorectal adenoma risk was found to depend on site, nitrosylation or not, and the ratio with the NEAC. IMPACT: These results emphasize the need for a global assessment of diet when considering nutritional prevention of colorectal carcinogenesis. Cancer Epidemiol Biomarkers Prev; 25(4); 640-7. (c)2016 AACR. PMID- 26823475 TI - Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort. AB - BACKGROUND: Chronic inflammation and oxidative stress are thought to be involved in colorectal cancer development. These processes may contribute to leakage of bacterial products, such as lipopolysaccharide (LPS) and flagellin, across the gut barrier. The objective of this study, nested within a prospective cohort, was to examine associations between circulating LPS and flagellin serum antibody levels and colorectal cancer risk. METHODS: A total of 1,065 incident colorectal cancer cases (colon, n = 667; rectal, n = 398) were matched (1:1) to control subjects. Serum flagellin- and LPS-specific IgA and IgG levels were quantitated by ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI), adjusting for multiple relevant confouding factors. RESULTS: Overall, elevated anti-LPS and anti-flagellin biomarker levels were not associated with colorectal cancer risk. After testing potential interactions by various factors relevant for colorectal cancer risk and anti-LPS and anti-flagellin, sex was identified as a statistically significant interaction factor (Pinteraction < 0.05 for all the biomarkers). Analyses stratified by sex showed a statistically significant positive colorectal cancer risk association for men (fully-adjusted OR for highest vs. lowest quartile for total anti-LPS + flagellin, 1.66; 95% CI, 1.10-2.51; Ptrend, 0.049), whereas a borderline statistically significant inverse association was observed for women (fully-adjusted OR, 0.70; 95% CI, 0.47-1.02; Ptrend, 0.18). CONCLUSION: In this prospective study on European populations, we found bacterial exposure levels to be positively associated to colorectal cancer risk among men, whereas in women, a possible inverse association may exist. IMPACT: Further studies are warranted to better clarify these preliminary observations. PMID- 26823478 TI - Intrathecal Injections in Children With Spinal Muscular Atrophy: Nusinersen Clinical Trial Experience. AB - Nusinersen (ISIS-SMNRx or ISIS 396443) is an antisense oligonucleotide drug administered intrathecally to treat spinal muscular atrophy. We summarize lumbar puncture experience in children with spinal muscular atrophy during a phase 1 open-label study of nusinersen and its extension. During the studies, 73 lumbar punctures were performed in 28 patients 2 to 14 years of age with type 2/3 spinal muscular atrophy. No complications occurred in 50 (68%) lumbar punctures; in 23 (32%) procedures, adverse events were attributed to lumbar puncture. Most common adverse events were headache (n = 9), back pain (n = 9), and post-lumbar puncture syndrome (n = 8). In a subgroup analysis, adverse events were more frequent in older children, children with type 3 spinal muscular atrophy, and with a 21- or 22-gauge needle compared to a 24-gauge needle or smaller. Lumbar punctures were successfully performed in children with spinal muscular atrophy; lumbar puncture related adverse event frequency was similar to that previously reported in children. PMID- 26823479 TI - Subsite distribution of colon cancer from Cancer Incidence in Five Continents Vol. X. PMID- 26823480 TI - Atrial Fibrillation Complexity Parameters Derived From Surface ECGs Predict Procedural Outcome and Long-Term Follow-Up of Stepwise Catheter Ablation for Atrial Fibrillation. AB - BACKGROUND: The success rate of catheter ablation for persistent atrial fibrillation (AF) is still far from satisfactory. Identification of patients who will benefit from ablation is highly desirable. We investigated the predictive value of noninvasive AF complexity parameters derived from standard 12-lead ECGs for AF termination and long-term success of catheter ablation and compared them with clinical predictors. METHODS AND RESULTS: The study included a training (93 patients) and a validation set (81 patients) of patients with persistent AF undergoing stepwise radiofrequency ablation. In the training set AF terminated in 81% during catheter ablation, 77% were in sinus rhythm after 6 years and multiple ablations. ECG-derived complexity parameters were determined from a baseline 10-s 12-lead ECG. Prediction of AF termination was similar using only ECG (cross validated mean area under the curve [AUC], 0.76+/-0.15) or only clinical parameters (mean AUC, 0.75+/-0.16). The combination improved prediction to a mean AUC of 0.79+/-0.13. Using a combined model of ECG and clinical parameters, sinus rhythm at long-term follow-up could be predicted with a mean AUC of 0.71+/-0.12. In the validation set AF terminated in 57%, 61% were in sinus rhythm after 4.6 years. The combined models predicted termination with an AUC of 0.70 and sinus rhythm at long-term follow-up with an AUC of 0.61. Overall, fibrillation-wave amplitude provided the best rhythm prediction. CONCLUSIONS: The predictive performance of ECG-derived AF complexity parameters for AF termination and long term success of catheter ablation in patients with persistent AF is at least as good as known clinical predictive parameters, with fibrillation-wave amplitude as the best predictor. PMID- 26823481 TI - (p)ppGpp-dependent and -independent pathways for salt tolerance in Escherichia coli. AB - Addition of some kinds of translation inhibitors targeting the ribosome such as kasugamycin to the culture medium as well as removal of a ribosome maturation factor or a ribosomal protein provides Escherichia coli cells with tolerance to high salt stress. Here, we found that another kind of translation inhibitor, serine hydroxamate (SHX), which induces amino acid starvation leading to (p)ppGpp production, also has a similar effect, but via a different pathway. Unlike kasugamycin, SHX was not effective in (p)ppGpp-null mutant cells. SHX and depletion of RsgA, a ribosome maturation factor, had an additive effect on salt tolerance, while kasugamycin or depletion of RsgA did not. These results indicate the presence of two distinct pathways, (p)ppGpp-dependent and -independent pathways, for salt tolerance of E. coli cell. Both pathways operate even in the absence of sigma(S), an alternative sigma factor involved in the stationary phase or stress response. Hastened activation of the exocytoplasmic stress-specific sigma factor, sigma(E), after salt shock was observed in the cells treated with SHX, as has been observed in the cells treated with a translation inhibitor or depleted of a ribosome maturation factor. PMID- 26823483 TI - Identifying and Promoting Hope in Patients. PMID- 26823482 TI - A/T gap tolerance in the core sequence and flanking sequence requirements of non canonical p53 response elements. AB - The canonical core sequence of the p53 response element, CATG, has a two-base A/T gap. Previously, we found that p53 can also activate a non-canonical four-base A/T gap CATATG core sequence. In this study, we investigated the possible number of A/T bases used by p53 and showed that a six-base A/T gap CATATATG core sequence was the maximum A/T gap in the p53 response element that could be upregulated by p53 and p63. Canonical and non-canonical p53 response elements also have three-base flanking sequences. A/T bases could be substituted by G/C bases, including CACACG and CGTGTG, but not CGCGCG. We found that the SV40 promoter with functional six- and two-base A/T gap core sequences could be activated by TAp63gamma and that TAp63gamma could upregulate SV40 small and large T antigens expression in COS7 cells. We also found that the distal region of PUMA promoter with functional two six-base A/T gap core sequences could be activated by TAp63gamma in 293T cells. These new findings could provide novel rules for the non-canonical p53 family response element and could extend the entire p53 family regulation network. PMID- 26823484 TI - Impact of Diabetic Status on Outcomes After Revascularization With Drug-Eluting Stents in Relation to Coronary Artery Disease Complexity: Patient-Level Pooled Analysis of 6081 Patients. AB - BACKGROUND: Diabetes mellitus and angiographic coronary artery disease complexity are intertwined and unfavorably affect prognosis after percutaneous coronary interventions, but their relative impact on long-term outcomes after percutaneous coronary intervention with drug-eluting stents remains controversial. This study determined drug-eluting stents outcomes in relation to diabetic status and coronary artery disease complexity as assessed by the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score. METHODS AND RESULTS: In a patient-level pooled analysis from 4 all-comers trials, 6081 patients were stratified according to diabetic status and according to the median SYNTAX score <=11 or >11. The primary end point was major adverse cardiac events, a composite of cardiac death, myocardial infarction, and clinically indicated target lesion revascularization within 2 years. Diabetes mellitus was present in 1310 patients (22%), and new generation drug-eluting stents were used in 4554 patients (75%). Major adverse cardiac events occurred in 173 diabetics (14.5%) and 436 nondiabetic patients (9.9%; P<0.001). In adjusted Cox regression analyses, SYNTAX score and diabetes mellitus were both associated with the primary end point (P<0.001 and P=0.028, respectively; P for interaction, 0.07). In multivariable analyses, diabetic versus nondiabetic patients had higher risks of major adverse cardiac events (hazard ratio, 1.25; 95% confidence interval, 1.03-1.53; P=0.026) and target lesion revascularization (hazard ratio, 1.54; 95% confidence interval, 1.18-2.01; P=0.002) but similar risks of cardiac death (hazard ratio, 1.41; 95% confidence interval, 0.96-2.07; P=0.08) and myocardial infarction (hazard ratio, 0.89; 95% confidence interval, 0.64-1.22; P=0.45), without significant interaction with SYNTAX score <=11 or >11 for any of the end points. CONCLUSIONS: In this population treated with predominantly new-generation drug-eluting stents, diabetic patients were at increased risk for repeat target-lesion revascularization consistently across the spectrum of disease complexity. The SYNTAX score was an independent predictor of 2-year outcomes but did not modify the respective effect of diabetes mellitus. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00297661, NCT00389220, NCT00617084, and NCT01443104. PMID- 26823485 TI - Systematic Review and Meta-analysis of Randomized Controlled Trials of Paclitaxel Coated Balloon Angioplasty in the Femoropopliteal Arteries: Role of Paclitaxel Dose and Bioavailability. AB - PURPOSE: To provide a qualitative analysis and quantitative synthesis of randomized controlled trials (RCTs) investigating paclitaxel-coated balloons (PCBs) in the femoropopliteal artery. METHODS: PubMed, EMBASE, AMED, Scopus, CENTRAL, online content, and abstracts from international meetings were last screened in April 2015 for eligible RCTs using the PRISMA selection process. Risk of bias was assessed using the Cochrane Collaboration's tool, and quality of evidence was evaluated with the GRADE system. Outcome measures included late lumen loss (LLL) at 6 months and event rates of major limb amputations, binary lesion restenosis, and target lesion revascularization (TLR). Pooled treatment effects were analyzed in a random effects model to account for clinical heterogeneity; the outcomes are presented as the rate ratios (RRs) and their 95% confidence intervals (CIs). Extensive meta-regression was performed to analyze potential confounders. The review was registered in the PROSPERO database (CRD42015023938; www.crd.york.ac.uk/PROSPERO). RESULTS: Eleven RCTs with 1609 subjects (1403 claudicants and 206 patients with critical limb ischemia) with medium-length femoropopliteal lesions (mean range 5.1-11.9 cm) were included. There was consistently high-quality evidence supporting the clear superiority of PCBs in terms of reduced LLL (mean difference -0.89 mm, 95% CI -1.14 to -0.64, p<0.001), less binary restenosis (RR 0.47, 95% CI 0.37 to 0.61, p<0.001), and fewer TLR events (RR 0.33, 95% CI 0.22 to 0.49, p<0.001). Major amputations were rare in both active and control arms (pooled event rate: 0.7%, 95% CI 0.3% to 1.2%). Results were stable across all potential risk modifiers and in the presence of stents as well. There was high-quality evidence that the dose of paclitaxel was related to the magnitude of the treatment effect; standard dose (3.0-MUg and 3.5-MUg) PCBs were significantly more effective compared with low dose 2-MUg PCB in reducing both restenosis (RR 2.1, 95% CI 1.2 to 3.4, p<0.001) and TLR (RR 2.5, 95% CI 1.9 to 3.8, p<0.001). CONCLUSION: PCBs reduce by more than half the rates of restenosis and TLR in the femoropopliteal artery regardless of stent placement. Biologic effect size may vary according to paclitaxel bioavailability. PMID- 26823486 TI - Simultaneous Bilateral vs Unilateral Carotid Artery Stenting: 30-Day and 1-Year Results. AB - PURPOSE: To evaluate clinical outcomes of simultaneous bilateral carotid artery stenting (sbCAS) compared with unilateral CAS (uCAS). METHODS: The database in our institution was queried to identify all patients treated with CAS from January 2005 to December 2012. In this time frame, 120 (18.8%) patients (mean age 64.9 +/- 7.7 years; 96 men) underwent sbCAS and 517 (81.2%) patients (mean age 65.7 +/- 7.7 years; 421 men) received uCAS. The primary endpoint was the composite of stroke, myocardial infarction, or death within 30 days or any ipsilateral stroke within 1 year. RESULTS: There was no significant difference in the rates of the primary endpoint between the sbCAS and uCAS groups (6.7% vs 4.6%, p=0.358). The rates of the primary endpoint among symptomatic patients was 8.0% in the sbCAS group and 5.0% in the uCAS group (p=0.299) and 3.1% and 4.0%, respectively (p=0.821) among asymptomatic patients. During the 30-day periprocedural period, the rates of the primary endpoint did not differ significantly between the sbCAS and uCAS groups among all patients (5.8% vs 4.4%, p=0.479), symptomatic patients (6.8% vs 5.0%, p=0.594), or asymptomatic patients (3.1% vs 3.5%, p>0.999). After this period, the incidences of any ipsilateral stroke were similarly low (0.8% and 0.2%, respectively; p=0.342). CONCLUSION: The study showed that simultaneous bilateral CAS had no more adverse events than unilateral CAS during the periprocedural period or within 1 year. This 1-stage strategy may become a valuable alternative in the treatment of patients with severe bilateral carotid stenosis. PMID- 26823487 TI - Ligand-dependent serum response factor activation by the human CC chemokine receptors CCR2a and CCR2b is mediated by G proteins of the Gq family. AB - Expression of the human CCR2 receptors, CCR2a and CCR2b, in mammalian cells results in ligand-dependent changes in the activity of multiple cellular signal transduction pathways, mediated in most cases by pertussis toxin-sensitive heterotrimeric G proteins of the Gi/o subfamily. In addition, CCR2a and CCR2b receptors have been shown to couple to Gq family members, triggering the canonical activation of phospholipase Cbeta isoenzymes. Activation of pertussis toxin-insensitive Gq proteins by cell-surface receptors is not only coupled to activation of phospholipase isoenzymes but also to Rho guanine nucleotide exchange factors, which in turn mediate activation of the Rho GTPases. Activated Rho GTPases regulate numerous cellular functions, including the organization of the actin cytoskeleton and gene transcription, such as the transcription factor serum response factor. These findings prompted us to investigate whether CCR2a and/or CCR2b stimulate serum response factor activity. The results presented herein demonstrate that stimulation of human CCR2a- or CCR2b-expressing COS-7 cells caused a vigorous induction of serum response factor activity. This effect was specifically mediated by Gq and/or G14, as well as Rho A and/or a closely related Rho GTPase. Furthermore, the stimulatory effect of CCR2a and CCR2b and Galphaq was sensitive to coexpression of the Galphaq-interacting leukemia associated Rho guanine nucleotide exchange factor. The findings of the work indicate a role for Galphaq and/or Galpha14 and in CCR2a/CCR2b-stimulated Rho A GTPase-mediated serum response factor activation and introduce a noncanonical pathway activated by CCR2 receptors by coupling to Gq proteins. PMID- 26823488 TI - Control of influenza infection is impaired by diminished interferon-gamma secretion by CD4 T cells in the lungs of toddler mice. AB - Respiratory viral infections, such as influenza, can lead to delayed viral clearance in toddlers, possibly exacerbating disease morbidity. We hypothesized that defective CD4 T cells in toddlers may contribute to a failure to clear virus at a similar rate to adults. Thus, we developed a young mouse model to examine potential divergent responses between toddlers and adults. We determined that young mice (toddler mice, 21 d old) were actively generating and recruiting effector/memory T cells, whereas memory populations were firmly established in older, adult mice (8-10 wk old). We infected toddler and adult mice with influenza A/PR8/34 (H1N1) and found young mice had elevated morbidity, as measured by enhanced weight loss and lower partial pressure of oxygen levels, throughout the infection, thus, modeling the higher morbidity observed in children (<2 y old) during infection. Early viral loads were comparable to adult mice, but toddler mice failed to clear virus by 10 d postinfection. This delayed clearance corresponded to poor lung recruitment of CD4 T cells, lower antiviral T cell responses, and lower B cell/antibodies in the lungs. Mechanistically, diminished interferon-gamma was detected in the lungs of toddler mice throughout the infection and corresponded to intrinsic, rather than extrinsic, CD4 T cell limitations in interferon-gamma transcription. Moreover, defects in interferon gamma production appeared downstream from signal transducer and activator of transcription 4 in the interleukin-12 signaling pathway, suggesting maturational delays different from neonates. Importantly, recombinant interferon-gamma supplementation rescued CD4 T cell numbers in the lungs and influenza-specific antibody formation. This study highlights the intrinsic limitations in CD4 T cell effector functions that may arise in toddlers and contribute to disease pathology. PMID- 26823489 TI - Activation of the Constitutive Androstane Receptor Increases the Therapeutic Index of CHOP in Lymphoma Treatment. AB - The constitutive androstane receptor (CAR and NR1i3) is a key regulator of CYP2B6, the enzyme predominantly responsible for the biotransformation of cyclophosphamide (CPA) to its pharmacologically active metabolite, 4 hydroxycyclophosphamide (4-OH-CPA). Previous studies from our laboratory illustrated that CAR activation increases the formation of 4-OH-CPA; however, CPA is rarely used clinically outside of combination therapies. Here, we hypothesize that including a selective human CAR activator with the CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen can improve the efficacy without exacerbating off-target toxicity of this regimen in non-Hodgkin lymphoma treatment. In this study, we have developed a novel multiorgan coculture system containing human primary hepatocytes for hepatic metabolism, lymphoma cells as a model target for CHOP, and cardiomyocytes as a major site of off-target toxicity associated with this regimen. We found that a selective human CAR activator, CITCO (6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4 dichlorobenzyl)oxime), altered expression of key drug-metabolizing enzymes and transporters in human hepatocytes, which positively affects the metabolic profile of CHOP. Coadministration of CITCO and CHOP in the coculture model led to significantly enhanced cytotoxicity in lymphoma cells but not in cardiomyocytes. Moreover, the beneficial effects of CITCO were abrogated when CAR knockout HepaRG cells were used in the coculture model. Importantly, synergistic anticancer effects were observed between CITCO and CHOP, in that inclusion of CITCO alongside the CHOP regimen offers comparable antineoplastic activity toward lymphoma cells at significantly reduced drug concentrations, and the decreased CHOP load attenuates cardiotoxicity. Overall, these findings provide a potentially promising novel strategy for facilitating CHOP-based chemotherapy. PMID- 26823490 TI - Phase I Study of DMOT4039A, an Antibody-Drug Conjugate Targeting Mesothelin, in Patients with Unresectable Pancreatic or Platinum-Resistant Ovarian Cancer. AB - DMOT4039A, a humanized anti-mesothelin mAb conjugated to the antimitotic agent monomethyl auristatin E (MMAE), was given to patients with pancreatic and ovarian cancer every 3 weeks (0.2-2.8 mg/kg; q3w) or weekly (0.8-1.2 mg/kg). A 3+3 design was used for dose escalation followed by expansion at the recommended phase II dose (RP2D) to evaluate safety and pharmacokinetics. Antitumor response was evaluated per RECIST 1.1 and serum CA19-9 or CA125 declines. Tumor mesothelin expression was determined by IHC. Seventy-one patients (40 pancreatic cancer; 31 ovarian cancer) were treated with DMOT4039A. For the q3w schedule (n = 54), the MTD and RP2D was 2.4 mg/kg, with dose-limiting toxicities of grade 3 hyperglycemia and grade 3 hypophosphatemia at 2.8 mg/kg. For the weekly schedule (n = 17), the maximum assessed dose was 1.2 mg/kg, with further dose escalations deferred because of toxicities limiting scheduled retreatment in later cycles, and therefore the RP2D level for the weekly regimen was determined to be 1 mg/kg. Across both schedules, the most common toxicities were gastrointestinal and constitutional. Treatment-related serious adverse events occurred in 6 patients; 4 patients continued treatment following dose reductions. Drug exposure as measured by antibody-conjugated MMAE and total antibody was generally dose proportional over all dose levels on both schedules. A total of 6 patients had confirmed partial responses (4 ovarian; 2 pancreatic) with DMOT4039A at 2.4 to 2.8 mg/kg i.v. q3w. DMOT4039A administered at doses up to 2.4 mg/kg q3w and 1.0 mg/kg weekly has a tolerable safety profile and antitumor activity in both pancreatic and ovarian cancer. PMID- 26823491 TI - Tigecycline Inhibits Glioma Growth by Regulating miRNA-199b-5p-HES1-AKT Pathway. AB - Tigecycline is a broad-spectrum, first-in-class glycylcycline antibiotic currently used to treat complicated skin infections and community-acquired pneumonia. However, there is accumulating evidence showing that tigecycline has anticancer properties. In this study, we found tigecycline could inhibit cell proliferation by inducing cell-cycle arrest, but not apoptosis in glioma. To find the underlying mechanism of how tigecycline inhibits cell proliferation, the expression of miRNAs, which were related to regulating cell-cycle progression, was detected with miRNA assay. We found that miR-199b-5p expression was significantly increased after tigecycline treatment, and miR-199b-5p target gene HES1 was downregulated. In addition, the PI3K/AKT pathway was inhibited and p21 expression was increased. When treated with tigecycline and miR-199b-5p antagomir simultaneously in glioma cells, we found that miR-199b-5p antagomir could partly block the effects induced by tigecycline. Tigecycline effectively upregulated miR 199b-5p expression and inhibited tumor growth in the xenograft tumor model of U87 glioma cells. These results suggest that tigecycline may induce cell-cycle arrest and inhibit glioma growth by regulating miRNA-199b-5p-HES1-AKT pathway. Thus, tigecycline is a promising agent in the treatment of malignant gliomas. PMID- 26823492 TI - Enhancing the Tumor Selectivity of a Picornavirus Virotherapy Promotes Tumor Regression and the Accumulation of Infiltrating CD8+ T Cells. AB - Picornaviruses have emerged as promising cancer therapies due to their ability to drive cytotoxic cellular immune responses and for promoting oncolysis. These properties include preferential replication in tumor cells, the induction of strong innate and adaptive immune responses, and the ease with which their genomes can be manipulated. We have developed Theiler's murine encephalomyelitis virus (TMEV) as an immunotherapy vector that promotes strong adaptive immune responses to tumor antigens embedded within its genome. To further explore its usefulness as cancer therapy, we investigated whether direct intratumoral delivery of TMEV could promote tumor regression. We generated several picornavirus hybrids using substrains of TMEV that have unique immunopathologic characteristics, despite their extensive sequence homology. These hybrids exhibit a unique propensity to infect and replicate in melanoma. We have identified GD7 KS1, a virus that is particularly effective at replicating and infecting B16 melanoma in vitro and provides benefit as an oncolytic therapy in vivo after intratumoral injection. In addition, this virus promotes the mobilization and accumulation of CD8(+) T cells within treated tumors. Altogether, these findings demonstrate that picornavirus substrains can be used to rationally design virus hybrids that promote antitumor responses and add to the known strategies identified by us and others to further enhance the therapeutic potential of vectors used to treat cancer. PMID- 26823493 TI - Posaconazole, a Second-Generation Triazole Antifungal Drug, Inhibits the Hedgehog Signaling Pathway and Progression of Basal Cell Carcinoma. AB - Deregulation of Hedgehog (Hh) pathway signaling has been associated with the pathogenesis of various malignancies, including basal cell carcinomas (BCC). Inhibitors of the Hh pathway currently available or under clinical investigation all bind and antagonize Smoothened (SMO), inducing a marked but transient clinical response. Tumor regrowth and therapy failure were attributed to mutations in the binding site of these small-molecule SMO antagonists. The antifungal itraconazole was demonstrated to be a potent SMO antagonist with a distinct mechanism of action from that of current SMO inhibitors. However, itraconazole represents a suboptimal therapeutic option due to its numerous drug drug interactions. Here, we show that posaconazole, a second-generation triazole antifungal with minimal drug-drug interactions and a favorable side-effect profile, is also a potent inhibitor of the Hh pathway that functions at the level of SMO. We demonstrate that posaconazole inhibits the Hh pathway by a mechanism distinct from that of cyclopamine and other cyclopamine-competitive SMO antagonists but, similar to itraconazole, has robust activity against drug resistant SMO mutants and inhibits the growth of Hh-dependent BCC in vivo Our results suggest that posaconazole, alone or in combination with other Hh pathway antagonists, may be readily tested in clinical studies for the treatment of Hh dependent cancers. Mol Cancer Ther; 15(5); 866-76. (c)2016 AACR. PMID- 26823494 TI - Modeling Therapy Response and Spatial Tissue Distribution of Erlotinib in Pancreatic Cancer. AB - Pancreatic ductal adenocarcinoma (PDAC) is likely the most aggressive and therapy resistant of all cancers. The aim of this study was to investigate the emerging technology of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) as a powerful tool to study drug delivery and spatial tissue distribution in PDAC. We utilized an established genetically engineered mouse model of spontaneous PDAC to examine the distribution of the small-molecule inhibitor erlotinib in healthy pancreas and PDAC. MALDI IMS was utilized on sections of single-dose or long-term-treated mice to measure drug tissue distribution. Histologic and statistical analyses were performed to correlate morphology, drug distribution, and survival. We found that erlotinib levels were significantly lower in PDAC compared with healthy tissue (P = 0.0078). Survival of long-term-treated mice did not correlate with overall levels of erlotinib or with overall histologic tumor grade but did correlate both with the percentage of atypical glands in the cancer (P = 0.021, rs = 0.59) and the level of erlotinib in those atypical glands (P = 0.019, rs = 0.60). The results of this pilot study present MALDI IMS as a reliable technology to study drug delivery and spatial distribution of compounds in a preclinical setting and support drug imaging-based translational approaches. Mol Cancer Ther; 15(5); 1145-52. (c)2016 AACR. PMID- 26823495 TI - GSK-3beta Governs Inflammation-Induced NFATc2 Signaling Hubs to Promote Pancreatic Cancer Progression. AB - We aimed to investigate the mechanistic, functional, and therapeutic role of glycogen synthase kinase 3beta (GSK-3beta) in the regulation and activation of the proinflammatory oncogenic transcription factor nuclear factor of activated T cells (NFATc2) in pancreatic cancer. IHC, qPCR, immunoblotting, immunofluorescence microscopy, and proliferation assays were used to analyze mouse and human tissues and cell lines. Protein-protein interactions and promoter regulation were analyzed by coimmunoprecipitation, DNA pulldown, reporter, and ChIP assays. Preclinical assays were performed using a variety of pancreatic cancer cells lines, xenografts, and a genetically engineered mouse model (GEMM). GSK-3beta-dependent SP2 phosphorylation mediates NFATc2 protein stability in the nucleus of pancreatic cancer cells stimulating pancreatic cancer growth. In addition to protein stabilization, GSK-3beta also maintains NFATc2 activation through a distinct mechanism involving stabilization of NFATc2-STAT3 complexes independent of SP2 phosphorylation. For NFATc2-STAT3 complex formation, GSK-3beta mediated phosphorylation of STAT3 at Y705 is required to stimulate euchromatin formation of NFAT target promoters, such as cyclin-dependent kinase-6, which promotes tumor growth. Finally, preclinical experiments suggest that targeting the NFATc2-STAT3-GSK-3beta module inhibits proliferation and tumor growth and interferes with inflammation-induced pancreatic cancer progression in Kras(G12D) mice. In conclusion, we describe a novel mechanism by which GSK-3beta fine-tunes NFATc2 and STAT3 transcriptional networks to integrate upstream signaling events that govern pancreatic cancer progression and growth. Furthermore, the therapeutic potential of GSK-3beta is demonstrated for the first time in a relevant Kras and inflammation-induced GEMM for pancreatic cancer. PMID- 26823496 TI - Long noncoding RNA MALAT1-derived mascRNA is involved in cardiovascular innate immunity. PMID- 26823497 TI - beta-Blockers in Atrial Fibrillation Patients With or Without Heart Failure: Association With Mortality in a Nationwide Cohort Study. AB - BACKGROUND: Recent data suggest that beta-blockers are associated with prognostic advantages in heart failure (HF) patients without concomitant atrial fibrillation (AF), but not in HF patients with concomitant AF. We aimed to investigate associations between beta-blocker treatment and cardiovascular outcome and mortality in AF patients with and without HF. METHODS AND RESULTS: Three nationwide registries were used to identify patients with nonvalvular AF patients with or without concomitant HF. Patients were stratified into beta-blocker users and beta-blocker nonusers, and according to the presence of a HF diagnosis. We followed the patients <= 5 years after baseline. Six different cardiovascular outcomes were investigated, including all-cause mortality and fatal thromboembolic events. Crude event rates were ascertained and propensity-matched Cox regression was used to compare event rates according to beta-blocker usage status. A total of 205,174 patients were included, where 39,741 patients had prevalent HF. In the latter subgroup of patients, the 1-year propensity-matched hazard ratio (HR) for all-cause mortality was 0.75 (95% confidence interval, 0.71 0.79; nontreated used as reference). For patients without concomitant HF, the propensity-matched HR for all-cause mortality was 0.78 (95% confidence interval, 0.71-0.76). CONCLUSIONS: In this large nationwide cohort study, evidence of a lower mortality with beta-blocker therapy in AF patients with concomitant HF was observed. In addition, this association was accompanied with indications that beta-blocker treatment is also associated with a better prognosis in AF patients without concomitant HF. PMID- 26823498 TI - Relation of QRS Duration to Clinical Benefit of Cardiac Resynchronization Therapy in Mild Heart Failure Patients Without Left Bundle Branch Block: The Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy Substudy. AB - BACKGROUND: There are conflicting data regarding the efficacy of cardiac resynchronization therapy (CRT) in patients with heart failure (HF) and without left bundle branch block. METHODS AND RESULTS: We evaluated the long-term clinical outcomes of 537 non-left bundle branch block patients with mild HF enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) study by QRS duration or morphology further stratified by PR interval. At 7 years of follow-up, the cumulative probability of HF hospitalization or death was 45% versus 56% among patients randomized to implantable cardioverter-defibrillator and CRT with defibrillator (CRT-D), respectively (P=0.209). Multivariable-adjusted subgroup analysis by QRS duration showed that patients from the lower quartile QRS duration group (<= 134 ms) experienced 2.4-fold (P=0.015) increased risk for HF hospitalization or death with CRT-D versus implantable cardioverter-defibrillator only therapy, whereas the effect of CRT-D in patients from the upper quartiles group (QRS>134 ms) was neutral (hazard ratio [HR] =0.97, P=0.86; P value for interaction =0.024). In a second analysis incorporating PR interval, patients with prolonged QRS (>134 ms) and prolonged PR (>230 ms) were protected with CRT-D (HR=0.31, P=0.003), whereas the association was neutral with prolonged QRS (>134 ms) and shorter PR (<= 230 ms;, HR=1.19, P=0.386; P value for interaction =0.002). The effect was neutral, regardless of morphology, right bundle branch block (HR=1.01, P=0.975), and intraventricular conduction delay (HR=1.31, P=0.172). CONCLUSIONS: Overall, patients with mild HF but without left bundle branch block morphology did not derive clinical benefit with CRT-D during long-term follow-up. Relatively shorter QRS was associated with a significantly increased risk with CRT-D relative to implantable cardioverter-defibrillator -only. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00180271, NCT01294449, and NCT02060110. PMID- 26823499 TI - High Levels of Resistance in the Common Bed Bug, Cimex lectularius (Hemiptera: Cimicidae), to Neonicotinoid Insecticides. AB - The rapid increase of bed bug populations resistant to pyrethroids demands the development of novel control tactics. Products combining pyrethroids and neonicotinoids have become very popular for bed bug control in the United States, but there are concerns about evolution of resistance to these compounds. Laboratory assays were used to measure the toxicity of topical applications of four neonicotinoids to a susceptible population and three pyrethroid-resistant populations. Activity of esterases, glutathione S-transferases, and cytochrome P450s of all strains was also evaluated. High levels of resistance to four neonicotinoids, acetamiprid, imidacloprid, dinotefuran, and thiamethoxam, relative to the susceptible Fort Dix population, were detected in populations collected from human dwellings in Cincinnati and Michigan. Because activity of detoxifying enzymes was increased in these two populations, our results suggest that these enzymes have some involvement in neonicotinoid resistance, but other resistance mechanisms might be involved as well. Detection of high levels of resistance to neonicotinoids further limits the options for chemical control of bed bugs. PMID- 26823501 TI - Defective histone supply causes condensin-dependent chromatin alterations, SAC activation and chromosome decatenation impairment. PMID- 26823500 TI - Pluralistic and stochastic gene regulation: examples, models and consistent theory. AB - We present a theory of pluralistic and stochastic gene regulation. To bridge the gap between empirical studies and mathematical models, we integrate pre-existing observations with our meta-analyses of the ENCODE ChIP-Seq experiments. Earlier evidence includes fluctuations in levels, location, activity, and binding of transcription factors, variable DNA motifs, and bursts in gene expression. Stochastic regulation is also indicated by frequently subdued effects of knockout mutants of regulators, their evolutionary losses/gains and massive rewiring of regulatory sites. We report wide-spread pluralistic regulation in ~800 000 tightly co-expressed pairs of diverse human genes. Typically, half of ~50 observed regulators bind to both genes reproducibly, twice more than in independently expressed gene pairs. We also examine the largest set of co expressed genes, which code for cytoplasmic ribosomal proteins. Numerous regulatory complexes are highly significant enriched in ribosomal genes compared to highly expressed non-ribosomal genes. We could not find any DNA-associated, strict sense master regulator. Despite major fluctuations in transcription factor binding, our machine learning model accurately predicted transcript levels using binding sites of 20+ regulators. Our pluralistic and stochastic theory is consistent with partially random binding patterns, redundancy, stochastic regulator binding, burst-like expression, degeneracy of binding motifs and massive regulatory rewiring during evolution. PMID- 26823502 TI - The K+-dependent GTPase Nug1 is implicated in the association of the helicase Dbp10 to the immature peptidyl transferase centre during ribosome maturation. AB - Ribosome synthesis employs a number of energy-consuming enzymes in both eukaryotes and prokaryotes. One such enzyme is the conserved circularly permuted GTPase Nug1 (nucleostemin in human). Nug1 is essential for 60S subunit assembly and nuclear export, but its role and time of action during maturation remained unclear. Based on in vitro enzymatic assays using the Chaetomium thermophilum (Ct) orthologue, we show that Nug1 exhibits a low intrinsic GTPase activity that is stimulated by potassium ions, rendering Nug1 a cation-dependent GTPase. In vivo we observe 60S biogenesis defects upon depletion of yeast Nug1 or expression of a Nug1 nucleotide-binding mutant. Most prominently, the RNA helicase Dbp10 was lost from early pre-60S particles, which suggested a physical interaction that could be reconstituted in vitro using CtNug1 and CtDbp10. In vivo rRNA-protein crosslinking revealed that Nug1 and Dbp10 bind at proximal and partially overlapping sites on the 60S pre-ribosome, most prominently to H89 that will constitute part of the peptidyl transferase center (PTC). The binding sites of Dbp10 are the same as those identified for the prokaryotic helicase DbpA bound to the 50S subunit. We suggest that Dbp10 and DbpA are performing a conserved role during PTC formation in all organisms. PMID- 26823504 TI - Randomized controlled trial of vertebroplasty versus kyphoplasty in the treatment of vertebral compression fractures. PMID- 26823503 TI - Complete resection of contrast-enhancing tumor volume is associated with improved survival in recurrent glioblastoma-results from the DIRECTOR trial. AB - BACKGROUND: The role of reoperation for recurrent glioblastoma (GBM) remains unclear. Prospective studies are lacking. Here, we studied the association of clinical outcome with extent of resection upon surgery for recurrent GBM in the patient cohort of DIRECTOR, a prospective randomized multicenter trial comparing 2 dose-intensified temozolomide regimens at recurrence of GBM. METHODS: We analyzed prospectively collected clinical and imaging data from the DIRECTOR cohort (N = 105). Volumetric analysis was performed on gadolinium contrast enhanced MRI as well as fluid attenuated inversion recovery/T2 MRI and correlated with PFS after initial progression (PFS2) and post-recurrence survival (PRS). Quality of life was monitored by the EORTC QLQ-C30 and QLQ-BN20 questionnaires at 8-week intervals. RESULTS: Seventy-one patients received surgery at first recurrence. Prognostic factors, including age, MGMT promoter methylation, and Karnofsky performance score, were balanced between patients with and without reoperation. Outcome in patients with versus without surgery at recurrence was similar for PFS2 (2.0 mo vs 1.9 mo, P = .360) and PRS (11.4 mo vs 9.8 mo, P = .633). Among reoperated patients, post-surgery imaging was available in 59 cases. In these patients, complete resection of contrast-enhancing tumor (N = 40) versus residual detection of contrast enhancement (N = 19) was associated with improved PRS (12.9 mo [95% CI: 11.5-18.2] vs 6.5 mo [95% CI: 3.6-9.9], P < .001) and better quality of life. Incomplete tumor resection was associated with inferior PRS compared with patients who did not undergo surgery (6.5 vs 9.8 mo, P = .052). Quality of life was similar in these 2 groups. CONCLUSION: Surgery at first recurrence of GBM improves outcome if complete resection of contrast-enhancing tumor is achieved. PMID- 26823505 TI - Dacie JV. Diagnosis and mechanism of hemolysis in chronic hemolytic anemia with nocturnal hemoglobinuria. AB - A leading British hematologist, John V. Dacie was known for his pioneering work on hemolytic disorders, especially paroxysmal nocturnal hemoglobinuria (PNH). In 1949, 12 years after the description of the Ham test for PNH, Dacie commented that "the essential basis of the disease is still a mystery." In this article, he demonstrated that the Ham test is highly dependent on acidification and requires a serum factor destroyed by heating. He concluded that PNH is a cell-intrinsic defect of erythrocytes that reflects a cell surface abnormality and requires heat labile serum factors. More than 40 years later, Kinoshita and colleagues reported that the defective surface expression of the glycosylphosphatidylinositol anchored proteins is caused by a somatic mutation of the PIG-A gene [Takeda J et al, Cell. 1993;73(4):703-711]. PMID- 26823506 TI - Mast cell differentiation: still open questions? AB - In this issue of Blood, Dahlin et al report on a minor circulating human mast cell (MC) progenitor cell population (lineage-negative [Lin ]/CD34hi/CD117int/hi/high-affinity immunoglobulin E receptor-positive [FcepsilonRI+]), with an immature MC-like appearance, which is present in the peripheral blood (PB) of healthy individuals and of asthma subjects well controlled by treatment or with reduced lung function. PMID- 26823507 TI - Together for better? AB - In this issue of Blood, Mateos et al report that bortezomib plus melphalan and prednisone (VMP) and lenalidomide plus low-dose dexamethasone (Rd) administered in a sequential or an alternating scheme were equally active and induced comparable toxicities in elderly myeloma patients. PMID- 26823508 TI - Innate immune signaling in CLL. AB - In this issue of Blood, Wagner et al describe a complex signaling model that explains the mechanism of action of a long-known prognostic marker in chronic lymphocytic leukemia (CLL) and integrates its function with the innate immune system and B-cell receptor signaling. PMID- 26823509 TI - BCR engagement in CLL: when translation goes wrong. AB - In this issue of Blood, Yeomans et al identify MYC as an important target for translational regulation in chronic lymphocytic leukemia (CLL) cells after B-cell receptor (BCR) stimulation and show that current therapies suppress this induction. PMID- 26823510 TI - Transfusion-related sepsis: a silent epidemic. AB - In this issue of Blood, Hong et al advocate for use of additional US Food and Drug Administration (FDA)-approved safety measures for transfusion. Most patients transfused with contaminated platelets do not show immediate clinical signs. Active surveillance suggests patient risk 10- to 40-fold higher than passive hemovigilance. PMID- 26823511 TI - The tactile motion aftereffect suggests an intensive code for speed in neurons sensitive to both speed and direction of motion. AB - Neurophysiological studies in primates have found that direction-sensitive neurons in the primary somatosensory cortex (SI) generally increase their response rate with increasing speed of object motion across the skin and show little evidence of speed tuning. We employed psychophysics to determine whether human perception of motion direction could be explained by features of such neurons and whether evidence can be found for a speed-tuned process. After adaptation to motion across the skin, a subsequently presented dynamic test stimulus yields an impression of motion in the opposite direction. We measured the strength of this tactile motion aftereffect (tMAE) induced with different combinations of adapting and test speeds. Distal-to-proximal or proximal-to distal adapting motion was applied to participants' index fingers using a tactile array, after which participants reported the perceived direction of a bidirectional test stimulus. An intensive code for speed, like that observed in SI neurons, predicts greater adaptation (and a stronger tMAE) the faster the adapting speed, regardless of the test speed. In contrast, speed tuning of direction-sensitive neurons predicts the greatest tMAE when the adapting and test stimuli have matching speeds. We found that the strength of the tMAE increased monotonically with adapting speed, regardless of the test speed, showing no evidence of speed tuning. Our data are consistent with neurophysiological findings that suggest an intensive code for speed along the motion processing pathways comprising neurons sensitive both to speed and direction of motion. PMID- 26823512 TI - Neuronal coupling by endogenous electric fields: cable theory and applications to coincidence detector neurons in the auditory brain stem. AB - The ongoing activity of neurons generates a spatially and time-varying field of extracellular voltage (Ve). This Ve field reflects population-level neural activity, but does it modulate neural dynamics and the function of neural circuits? We provide a cable theory framework to study how a bundle of model neurons generates Ve and how this Ve feeds back and influences membrane potential (Vm). We find that these "ephaptic interactions" are small but not negligible. The model neural population can generate Ve with millivolt-scale amplitude, and this Ve perturbs the Vm of "nearby" cables and effectively increases their electrotonic length. After using passive cable theory to systematically study ephaptic coupling, we explore a test case: the medial superior olive (MSO) in the auditory brain stem. The MSO is a possible locus of ephaptic interactions: sounds evoke large (millivolt scale)Vein vivo in this nucleus. The Ve response is thought to be generated by MSO neurons that perform a known neuronal computation with submillisecond temporal precision (coincidence detection to encode sound source location). Using a biophysically based model of MSO neurons, we find millivolt-scale ephaptic interactions consistent with the passive cable theory results. These subtle membrane potential perturbations induce changes in spike initiation threshold, spike time synchrony, and time difference sensitivity. These results suggest that ephaptic coupling may influence MSO function. PMID- 26823513 TI - Immediate manifestation of acoustic trauma in the auditory cortex is layer specific and cell type dependent. AB - Exposure to loud sounds damages the auditory periphery and induces maladaptive changes in central parts of the auditory system. Diminished peripheral afferentation and altered inhibition influence the processing of sounds in the auditory cortex. It is unclear, however, which types of inhibitory interneurons are affected by acoustic trauma. Here we used single-unit electrophysiological recording and two-photon calcium imaging in anesthetized mice to evaluate the effects of acute acoustic trauma (125 dB SPL, white noise, 5 min) on the response properties of neurons in the core auditory cortex. Electrophysiological measurements suggested the selective impact of acoustic trauma on inhibitory interneurons in the auditory cortex. To further investigate which interneuronal types were affected, we used two-photon calcium imaging to record the activity of neurons in cortical layers 2/3 and 4, specifically focusing on parvalbumin positive (PV+) and somatostatin-positive (SST+) interneurons. Spontaneous and pure-tone-evoked firing rates of SST+ interneurons increased in layer 4 immediately after acoustic trauma and remained almost unchanged in layer 2/3. Furthermore, PV+ interneurons with high best frequencies increased their evoked to-spontaneous firing rate ratios only in layer 2/3 and did not change in layer 4. Finally, acoustic trauma unmasked low-frequency excitatory inputs only in layer 2/3. Our results demonstrate layer-specific changes in the activity of auditory cortical inhibitory interneurons within minutes after acoustic trauma. PMID- 26823514 TI - Properties and physiological function of Ca2+-dependent K+ currents in uniglomerular olfactory projection neurons. AB - Ca(2+)-activated potassium currents [IK(Ca)] are an important link between the intracellular signaling system and the membrane potential, which shapes intrinsic electrophysiological properties. To better understand the ionic mechanisms that mediate intrinsic firing properties of olfactory uniglomerular projection neurons (uPNs), we used whole cell patch-clamp recordings in an intact adult brain preparation of the male cockroach Periplaneta americana to analyze IK(Ca) In the insect brain, uPNs form the principal pathway from the antennal lobe to the protocerebrum, where centers for multimodal sensory processing and learning are located. In uPNs the activation of IK(Ca) was clearly voltage and Ca(2+) dependent. Thus under physiological conditions IK(Ca) is strongly dependent on Ca(2+) influx kinetics and on the membrane potential. The biophysical characterization suggests that IK(Ca) is generated by big-conductance (BK) channels. A small-conductance (SK) channel-generated current could not be detected. IK(Ca) was sensitive to charybdotoxin (CTX) and iberiotoxin (IbTX) but not to apamin. The functional role of IK(Ca) was analyzed in occlusion experiments under current clamp, in which portions of IK(Ca) were blocked by CTX or IbTX. Blockade of IK(Ca) showed that IK(Ca) contributes significantly to intrinsic electrophysiological properties such as the action potential waveform and membrane excitability. PMID- 26823515 TI - Recording and labeling at a site along the cochlea shows alignment of medial olivocochlear and auditory nerve tonotopic mappings. AB - Medial olivocochlear (MOC) neurons provide an efferent innervation to outer hair cells (OHCs) of the cochlea, but their tonotopic mapping is incompletely known. In the present study of anesthetized guinea pigs, the MOC mapping was investigated using in vivo, extracellular recording, and labeling at a site along the cochlear course of the axons. The MOC axons enter the cochlea at its base and spiral apically, successively turning out to innervate OHCs according to their characteristic frequencies (CFs). Recordings made at a site in the cochlear basal turn yielded a distribution of MOC CFs with an upper limit, or "edge," due to usually absent higher-CF axons that presumably innervate more basal locations. The CFs at the edge, normalized across preparations, were equal to the CFs of the auditory nerve fibers (ANFs) at the recording sites (near 16 kHz). Corresponding anatomical data from extracellular injections showed spiraling MOC axons giving rise to an edge of labeling at the position of a narrow band of labeled ANFs. Overall, the edges of the MOC CFs and labeling, with their correspondences to ANFs, suggest similar tonotopic mappings of these efferent and afferent fibers, at least in the cochlear basal turn. They also suggest that MOC axons miss much of the position of the more basally located cochlear amplifier appropriate for their CF; instead, the MOC innervation may be optimized for protection from damage by acoustic overstimulation. PMID- 26823516 TI - Adaptive reliance on the most stable sensory predictions enhances perceptual feature extraction of moving stimuli. AB - The prediction of the sensory outcomes of action is thought to be useful for distinguishing self- vs. externally generated sensations, correcting movements when sensory feedback is delayed, and learning predictive models for motor behavior. Here, we show that aspects of another fundamental function-perception are enhanced when they entail the contribution of predicted sensory outcomes and that this enhancement relies on the adaptive use of the most stable predictions available. We combined a motor-learning paradigm that imposes new sensory predictions with a dynamic visual search task to first show that perceptual feature extraction of a moving stimulus is poorer when it is based on sensory feedback that is misaligned with those predictions. This was possible because our novel experimental design allowed us to override the "natural" sensory predictions present when any action is performed and separately examine the influence of these two sources on perceptual feature extraction. We then show that if the new predictions induced via motor learning are unreliable, rather than just relying on sensory information for perceptual judgments, as is conventionally thought, then subjects adaptively transition to using other stable sensory predictions to maintain greater accuracy in their perceptual judgments. Finally, we show that when sensory predictions are not modified at all, these judgments are sharper when subjects combine their natural predictions with sensory feedback. Collectively, our results highlight the crucial contribution of sensory predictions to perception and also suggest that the brain intelligently integrates the most stable predictions available with sensory information to maintain high fidelity in perceptual decisions. PMID- 26823517 TI - Selective IT neurons are selective along many dimensions. AB - Our visual abilities are unsurpassed because of a sophisticated code for objects located in the inferior temporal (IT) cortex. This code has remained a mystery because IT neurons show extremely diverse shape selectivity with no apparent organizing principle. Here, we show that there is an intrinsic component to selectivity in IT neurons. We tested IT neurons on distinct shapes and their parametric variations and asked whether neurons selective along one dimension were also selective along others. Selective neurons responded to fewer shapes and were narrowly tuned to local variations of these shapes, both along arbitrary morph lines and along variations in size, position, or orientation. For a subset of neurons, selective neurons were selective for both shape and texture. Finally, selective neurons were also more invariant in that they preserved their shape preferences across changes in size, position, and orientation. These observations indicate that there is an intrinsic constraint on the sharpness of tuning for the features coded by each IT neuron, making it always sharply tuned or always broadly tuned along all dimensions. We speculate that this may be an organizing principle throughout visual cortex. PMID- 26823518 TI - Dietary flavonoid intake and weight maintenance: three prospective cohorts of 124,086 US men and women followed for up to 24 years. AB - OBJECTIVE: To examine whether dietary intake of specific flavonoid subclasses (including flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, and flavonoid polymers) is associated with weight change over time. DESIGN: Three prospective cohort studies. SETTING: Health professionals in the United States. PARTICIPANTS: 124,086 men and women participating in the Health Professionals Follow-up Study (HPFS), Nurses' Health Study (NHS), and Nurses' Health Study II (NHS II). MAIN OUTCOME MEASURE: Self reported change in weight over multiple four year time intervals between 1986 and 2011. RESULTS: Increased consumption of most flavonoid subclasses, including flavonols, flavan-3-ols, anthocyanins, and flavonoid polymers, was inversely associated with weight change over four year time intervals, after adjustment for simultaneous changes in other lifestyle factors including other aspects of diet, smoking status, and physical activity. In the pooled results, the greatest magnitude of association was observed for anthocyanins (-0.23 (95% confidence interval -0.30 to -0.15) lbs per additional standard deviation/day, 10 mg), flavonoid polymers (-0.18 (-0.28 to -0.08) lbs per additional SD/day, 138 mg), and flavonols (-0.16 (-0.26 to -0.06) lbs per additional SD/day, 7 mg). After additional adjustment for fiber intake, associations remained significant for anthocyanins, proanthocyanidins, and total flavonoid polymers but were attenuated and no longer statistically significant for other subclasses. CONCLUSIONS: Higher intake of foods rich in flavonols, flavan-3-ols, anthocyanins, and flavonoid polymers may contribute to weight maintenance in adulthood and may help to refine dietary recommendations for the prevention of obesity and its potential consequences. PMID- 26823520 TI - Authors' reply to Al-Wali and Hughes. PMID- 26823519 TI - PPM1D Mosaic Truncating Variants in Ovarian Cancer Cases May Be Treatment-Related Somatic Mutations. AB - Mosaic truncating mutations in the protein phosphatase, Mg(2+)/Mn(2+)-dependent, 1D (PPM1D) gene have recently been reported with a statistically significantly greater frequency in lymphocyte DNA from ovarian cancer case patients compared with unaffected control patients. Using massively parallel sequencing (MPS) we identified truncating PPM1D mutations in 12 of 3236 epithelial ovarian cancer (EOC) case patients (0.37%) but in only one of 3431 unaffected control patients (0.03%) (P = .001). All statistical tests were two-sided. A combination of Sanger sequencing, pyrosequencing, and MPS data suggested that 12 of the 13 mutations were mosaic. All mutations were identified in post-chemotherapy treatment blood samples from case patients (n = 1827) (average 1234 days post-treatment in carriers) rather than from cases collected pretreatment (less than 14 days after diagnosis, n = 1384) (P = .002). These data suggest that PPM1D variants in EOC cases are primarily somatic mosaic mutations caused by treatment and are not associated with germline predisposition to EOC. PMID- 26823522 TI - NHS leader defends expansion of personal health budgets to 100,000 people by 2020. PMID- 26823523 TI - Detection of ubiquitous and heterogeneous mutations in cell-free DNA from patients with early-stage non-small-cell lung cancer. AB - BACKGROUND: The aim of this pilot study was to assess whether both ubiquitous and heterogeneous somatic mutations could be detected in cell-free DNA (cfDNA) from patients with early-stage non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Three stage I and one stage II primary NSCLC tumors were subjected to multiregion whole-exome sequencing (WES) and validated with AmpliSeq. A subset of ubiquitous and heterogeneous single-nucleotide variants (SNVs) were chosen. Multiplexed PCR using custom-designed primers, coupled with next-generation sequencing (mPCR-NGS), was used to detect these SNVs in both tumor DNA and cfDNA isolated from plasma obtained before surgical resection of the tumors. The limit of detection for each assay was determined using cfDNA from 48 presumed-normal healthy volunteers. RESULTS: Tumor DNA and plasma-derived cfDNA was successfully amplified and sequenced for 37/50 (74%) SNVs using the mPCR-NGS method. Twenty five (68%) were ubiquitous and 12 (32%) were heterogeneous SNVs. Variant detection by mPCR-NGS and WES-AmpliSeq in tumor tissue was well correlated (R(2) = 0.8722, P < 0.0001). Sixteen (43%) out of 37 SNVs were detected in cfDNA. Twelve of these were ubiquitous SNVs with a variant allele frequency (VAF) range of 0.15-23.25%, and four of these were heterogeneous SNVs with a VAF range of 0.28-1.71%. There was a statistically significant linear relationship between the VAFs for tumor and cfDNA (R(2) = 0.5144; P = 0.0018). For all four patients, at least two variants were detected in plasma. The estimated number of copies of variant DNA present in each sample ranged from 5 to 524. The average number of variant copies required for detection (VCRD) was 3.16 (range: 0.2-7.6 copies). CONCLUSIONS: The mPCR-NGS method revealed intratumor heterogeneity in early-stage NSCLC tumors, and was able to detect both ubiquitous and heterogeneous SNVs in cfDNA. Further validation of mPCR-NGS in cfDNA is required to define its potential use in clinical practice. PMID- 26823524 TI - Identifying the potential long-term survivors among breast cancer patients with distant metastasis. AB - BACKGROUND: We aimed to develop a prediction model to identify long-term survivors after developing distant metastasis from breast cancer. PATIENTS AND METHODS: From the institution's database, we collected data of 547 patients who developed distant metastasis during their follow-ups. We developed a model that predicts the post-metastasis overall survival (PMOS) based on the clinicopathologic factors of the primary tumors and the characteristics of the distant metastasis. For validation, the survival data of 254 patients from four independent institutions were used. RESULTS: The median duration of the PMOS was 31.0 months. The characteristics of the initial primary tumor, such as tumor stage, hormone receptor status, and Ki-67 expression level, and the characteristics of the distant metastasis presentation including the duration of disease-free interval, the site of metastasis, and the presence of metastasis related symptoms were independent prognostic factors determining the PMOS. The association between tumor stage and the PMOS was only seen in tumors with early relapses. The PMOS score, which was developed based on the above six factors, successfully identified patients with superior survival after metastasis. The median PMOS for patients with a PMOS score of <2 and for patients with a PMOS score of >5 were 71.0 and 12 months, respectively. The clinical significance of the PMOS score was further validated using independent multicenter datasets. CONCLUSIONS: We have developed a novel prediction model that can classify breast cancer patients with distant metastasis according to their survival after metastasis. Our model can be a valuable tool to identify long-term survivors who can be potential candidates for more intensive multidisciplinary approaches. Furthermore, our model can provide a more reliable survival information for both physicians and patients during their informed decision-making process. PMID- 26823521 TI - HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients. AB - BACKGROUND: We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. METHODS: Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. RESULTS: A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central South America. CONCLUSIONS: HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs. PMID- 26823526 TI - Skeletal Muscle Pathology in X-Linked Myotubular Myopathy: Review With Cross Species Comparisons. AB - X-linked myotubular myopathy (XLMTM) is a devastating, rare, congenital myopathy caused by mutations in the MTM1 gene, resulting in a lack of or dysfunction of the enzyme myotubularin. This leads to severe perinatal weakness and distinctive muscle pathology. It was originally thought that XLMTM was related to developmental arrest in myotube maturation; however, the generation and characterization of several animal models have significantly improved our understanding of clinical and pathological aspects of this disorder. Myotubularin is now known to participate in numerous cellular processes including endosomal trafficking, excitation-contraction coupling, cytoskeletal organization, neuromuscular junction structure, autophagy, and satellite cell proliferation and survival. The available vertebrate models of XLMTM, which vary in severity from complete absence to reduced functional levels of myotubularin, recapitulate features of the human disease to a variable extent. Understanding how pathological endpoints in animals with XLMTM translate to human patients will be essential to interpret preclinical treatment trials and translate therapies into human clinical studies. This review summarizes the published animal models of XLMTM, including those of zebrafish, mice, and dogs, with a focus on their pathological features as compared to those seen in human XLMTM patients. PMID- 26823527 TI - Rheumatoid arthritis, anti-tumour necrosis factor treatment, and risk of squamous cell and basal cell skin cancer: cohort study based on nationwide prospectively recorded data from Sweden. AB - OBJECTIVE: To investigate the risk of squamous cell and basal cell skin cancer in patients with rheumatoid arthritis naive to biologic drugs, in patients starting tumour necrosis factor (TNF) inhibitor treatment, and in the general population. DESIGN: Population based cohort study. SETTING: Nationwide data from Sweden. PARTICIPANTS: Cohort of patients with rheumatoid arthritis naive to biologics (n=46 409), cohort of patients with rheumatoid arthritis starting TNF inhibitor treatment as first biologic in 1998-2012 (n=12 558), and matched general population comparator cohort, identified through national quality of care and health registers. MAIN OUTCOME MEASURE: Hazard ratio of first in situ or invasive squamous cell skin cancer (1998-2012) and first basal cell cancer (2004-12). RESULTS: For basal cell cancer, the hazard ratio was 1.22 (95% confidence interval 1.07 to 1.41) comparing biologics-naive rheumatoid arthritis patients with the general population and 1.14 (0.98 to 1.33; 236 v 1587 events) comparing TNF inhibitor treated patients with biologics-naive patients. For squamous cell cancer, the hazard ratio was 1.88 (1.74 to 2.03) comparing biologics-naive rheumatoid arthritis patients with the general population and 1.30 (1.10 to 1.55; 191 v 847 events) comparing TNF inhibitors with biologics-naive patients; the latter translated to an annual number needed to harm in the order of 1600. Among people with a history of squamous cell or basal cell cancer, TNF inhibitors did not further increase risks. CONCLUSION: A small to moderately increased risk of basal cell cancer was seen in biologics-naive rheumatoid arthritis patients, with no further effect of TNF inhibitors. For squamous cell cancer, the risk was nearly doubled in biologics-naive patients, with a further 30% increase in risk among patients treated with TNF inhibitors; this translates to one additional case for every 1600 years of treatment experience, assuming that this association reflected causality. Vigilance regarding skin malignancies may be advisable in rheumatoid arthritis, irrespective of TNF inhibitor treatment. Most of the increase in risk for non-melanoma skin cancer in patients with rheumatoid arthritis treated with TNF inhibitors originates from factors other than that treatment. PMID- 26823528 TI - Dual regulation of root hydraulic conductivity and plasma membrane aquaporins by plant nitrate accumulation and high-affinity nitrate transporter NRT2.1. AB - The water status and mineral nutrition of plants critically determine their growth and development. Nitrate (NO3(-)), the primary nitrogen source of higher plants, is known to impact the water transport capacity of roots (root hydraulic conductivity, Lpr). To explore the effects and mode of action of NO3(-) on Lpr, we used an extended set of NO3(-) transport (nrt1.1, nrt1.2, nrt1.5 and nrt2.1), signaling (nrt1.1 and nrt2.1) and metabolism (nia) mutants in Arabidopsis, grown under various NO3(-) conditions. First, a strong positive relationship between Lpr and NO3(-) accumulation, in shoots rather than in roots, was revealed. Secondly, a specific 30% reduction of Lpr in nrt2.1 plants unraveled a major role for the high-affinity NO3(-) transporter NRT2.1 in increasing Lpr These results indicate that NO3(-)signaling rather than nitrogen assimilation products governs Lpr in Arabidopsis. Quantitative real-time reverse transcription-PCR and enzyme linked immunosorbent assays (ELISAs) were used to investigate the effects of NO3( ) availability on plasma membrane aquaporin (plasma membrane intrinsic protein; PIP) expression. Whereas PIP regulation mostly occurs at the post-translational level in wild-type plants, a regulation of PIPs at both the transcriptional and translational levels was uncovered in nrt2.1 plants. In conclusion, this work reveals that control of Arabidopsis Lpr and PIP functions by NO3(-) involves novel shoot to root signaling and NRT2.1-dependent functions. PMID- 26823525 TI - Prostate Cancer Susceptibility in Men of African Ancestry at 8q24. AB - The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00*10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38*10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04*10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39*10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region. PMID- 26823529 TI - Improving recognition of spondyloarthropathy in primary care: an unmet need. PMID- 26823530 TI - Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF). AB - OBJECTIVE: To develop widely accepted international severity score for children and adult patients with familial Mediterranean fever (FMF) that can be easily applied, in research and clinical practice. METHODS: Candidate severity criteria were suggested by several FMF expert physicians. After three rounds of Delphi survey, the candidate criteria, defined by the survey, were discussed by experts in a consensus meeting. Each expert brought data of clinical manifestations, laboratory findings and physician's global assessments (PGAs) of minimum 20 patients from their centres. We used the PGAs for disease severity as a gold standard. Logistic regression analysis was used to evaluate the predicting value of each item, and receiver operating characteristic curve analysis was performed to demonstrate the success of the criteria set. RESULTS: A total of 281 patients consist of 162 children and 119 adults with FMF were enrolled and available for validity analysis: Nine domains were included in the final core set of variables for the evaluation of disease severity in FMF. The International Severity Score for FMF (ISSF) may reach a maximum of 10 if all items are maximally scored. The threshold values to determine: severe disease >=6, intermediate disease 3-5, mild disease <=2. Area under the curve was calculated as 0.825 for this set in the whole group. CONCLUSIONS: The initial validity of ISSF both in children and adult with FMF was demonstrated. We anticipate that it will provide a robust tool to objectively define disease severity for clinical trials, future research as well as for therapeutic decisions in managing patients with FMF. PMID- 26823531 TI - Misrepresenting harms in antidepressant trials. PMID- 26823532 TI - A month for reflecting on suicide prevention. PMID- 26823533 TI - Methylphenidate for attention-deficit/hyperactivity disorder: Too much of a good thing? PMID- 26823535 TI - European Parliament rejects high sugar content in baby foods. PMID- 26823534 TI - Signs of deterioration in infants discharged home following congenital heart surgery in the first year of life: a qualitative study. AB - AIMS: To describe the ways in which parents recognise and make decisions about their child's symptoms following discharge home after congenital heart interventions in the first year of life and their experiences of seeking help. METHODS: This was a qualitative study involving semistructured interviews with parents. Twenty-one parents were recruited to the study. Parents all had a child who had congenital heart surgery in their first year of life between September 2009 and October 2013 at one of three UK cardiac centres; the children had either died or were readmitted as an emergency following initial discharge. RESULTS: Some parents were unable to identify any early warning signs. Others described symptoms of deterioration including changes in feeding and appearance, respiratory distress and subtle behavioural changes that may not be routinely highlighted to parents at discharge. Several barriers to accessing prompt medical assistance were identified including parents feeling that their concerns were not taken seriously, long wait times and lack of protocols at A&E. CONCLUSIONS: Our study highlights behavioural symptoms as being a potentially underemphasised sign of deterioration and identifies a number of barriers to parents accessing support when they are concerned. It is important that parents are encouraged to seek advice at the earliest opportunity and that those health professionals at the front line have access to the information they need in order to respond in an appropriate and timely way. A role for home monitoring was also noted as potentially useful in identifying at risk children who appear clinically well. PMID- 26823536 TI - Clinical assessment of the late-career medical practitioner. AB - OBJECTIVES: This paper is a guide to the general psychiatric assessment of the late career medical practitioner (LCP) from a clinical viewpoint. CONCLUSIONS: Late career is a specific developmental stage in medical practitioners, a time of transition towards retirement. The treating psychiatrist should be mindful of the welfare of the practitioner, the public and the profession during the assessment, which is conducted from a complex therapeutic and regulatory viewpoint. It is important to assess the physical, psychological and cognitive health of the LCP. Although rates of burnout, depression and suicidal ideation are lowest in Australian doctors over 60, only a small minority of LCPs over 75 are likely to perform at a cognitive level similar to that of younger colleagues. There are a number of therapeutic challenges, including the practitioner's acceptance of their own ageing. PMID- 26823537 TI - 'Nurse specialling': Direct nursing observation in the emergency department compared to other wards of an urban teaching hospital in Sydney. AB - OBJECTIVE: This study examined the patterns of direct observation of patients by nursing staff ('nurse specials') and compared those required for mental health/drug health (MH/DH)-related presentations to other patient groups in different care settings. METHODS: A retrospective review of nurse special shifts requested during the 2014 calendar year at an urban teaching hospital. RESULTS: Hospital-wide 14,021 8-hour nursing shifts were ordered for special observation of patients, an average of 39 per day. Of these, 30% were requested for MH/DH related presentations, with the majority (70%) required for medically unstable patients. However, of the 1917 shifts required in the emergency department, 1841 (96%) were for MH/DH presentations compared to 76 (4%) for patients with unrelated medical conditions (odds ratio 98.2; 95% confidence interval 77.71 124.06, P<0.0001). CONCLUSIONS: In contrast to the rest of the hospital, emergency department-based nurse special requests were significantly more likely to be for MH/DH presentations. This figure represents a considerable staff and financial burden and may be reduced by diversion or more rapid transfer of such presentations to an appropriate inpatient ward. PMID- 26823539 TI - A Quality Improvement Collaborative to Improve Pediatric Primary Care Genetic Services. AB - OBJECTIVE: To investigate if a national pediatric primary care quality improvement collaborative (QIC) could improve and sustain adherence with process measures related to diagnosis and management of children with genetic disorders. METHODS: Thirteen practices in 11 states from the American Academy of Pediatrics' Quality Improvement Innovation Networks participated in a 6-month QIC that included regular educational opportunities, access to genetic professionals, and performance feedback. The QIC identified 11 aims related to improving diagnosis and management of children with genetic disorders. The practices evaluated adherence by reviewing patient records at baseline, monthly for 6 months (active improvement period), and then once 6 months after the QIC's conclusion to check for sustainability. Random intercept binomial regression models with practice level random intercepts were used to compare adherence over time for each aim. RESULTS: During the active improvement period, statistically significant improvements in adherence were observed for 4 of the 7 aims achieving minimal data submission levels. For example, adherence improved for family histories created/maintained at health supervision visits documenting all components of the family history (6% vs 60%, P < .001), and for patients with specific genetic disorders who received recommended care (58% vs 85%, P < .001). All 4 of these aims also demonstrated statistically significant improvements during the sustainability period. CONCLUSIONS: A national QIC reveals promise in improving and sustaining adherence with process measures related to the diagnosis and management of genetic disorders. Future research should focus on patient outcome measures and the optimal number of aims to pursue in QICs. PMID- 26823540 TI - Safety and Immunogenicity of Sequential Rotavirus Vaccine Schedules. AB - BACKGROUND AND OBJECTIVES: Although both licensed rotavirus vaccines are safe and effective, it is often not possible to complete the schedule by using the same vaccine formulation. The goal of this study was to investigate the noninferiority of the immune responses to the 2 licensed rotavirus vaccines when administered as a mixed schedule compared with administering a single vaccine formulation alone. METHODS: Randomized, multicenter, open-label study. Healthy infants (6-14 weeks of age) were randomized to receive rotavirus vaccines in 1 of 5 different schedules (2 using a single vaccine for all doses, and 3 using mixed schedules). The group receiving only the monovalent rotavirus vaccine received 2 doses of vaccine and the other 4 groups received 3 doses of vaccine. Serum for immunogenicity testing was obtained 1 month after the last vaccine dose and the proportion of seropositive children (rotavirus immunoglobulin A >=20 U/mL) were compared in all the vaccine groups. RESULTS: Between March 2011 and September 2013, 1393 children were enrolled and randomized. Immune responses to all the sequential mixed vaccine schedules were shown to be noninferior when compared with the 2 single vaccine reference groups. The proportion of children seropositive to at least 1 vaccine antigen at 1 month after vaccination ranged from 77% to 96%, and was not significantly different among all the study groups. All schedules were well tolerated. CONCLUSIONS: Mixed schedules are safe and induced comparable immune responses when compared with the licensed rotavirus vaccines given alone. PMID- 26823541 TI - Concurrent Ulcerative Colitis and Neurofibromatosis Type 1: The Question of a Common Pathway. AB - Patients with neurofibromatosis type 1 (NF1) are prone to the development of gastrointestinal stromal tumors, which may present clinically with hematochezia, obstruction, or abdominal pain. These symptoms are also commonly associated with the presentation of ulcerative colitis (UC). Within the past 5 years, there have been 2 reports of concurrent NF1 and UC and a common pathophysiologic pathway involving mast cells has been postulated. We present the case of a 15-year-old boy with a known history of NF1 who presented with 3 months of hematochezia and loose stools. A colonoscopy revealed pancolitis and histology demonstrating acute cryptitis, focal crypt abscesses, and architectural distortion consistent with UC. Due to the paucity of reported cases, the findings of both diseases in the same individual could reasonably be discounted as coincidence. However, in light of increasing reports of concurrent NF1 and UC, advances in characterizing the microenvironment within neurofibromas, and recent findings regarding potential shared genetic susceptibility, it is increasingly possible that the proposed common pathway is accurate. Our case adds to the literature and underscores the need for further investigation. PMID- 26823542 TI - Rotavirus Vaccines-OK to Mix and Match. PMID- 26823543 TI - Infrared Microspectroscopy of Bionanomaterials (Diatoms) with Careful Evaluation of Void Effects. AB - In order to characterize a representative natural bionanomaterial, present day centric diatom samples (diameter, 175-310 um) have been analyzed and imaged by infrared (IR) micro-spectroscopy and scanning electron microscopy (SEM). Because diatom silica frustules have complex microscopic morphology, including many void areas such as micro- or nano-pores, the effects of voids on the spectral band shapes were first evaluated. With increasing void area percentage, 1220 cm( 1)/1070 cm(-1) peak height ratio (Si-O polymerization index) increases and 950 cm(-1)/800 cm(-1) peak height ratio (Si-OH/Si-O-Si) decreases, both approaching 1. Based on the void area percentage of representative diatom samples determined using SEM image analyses (51.5% to 20.5%) and spectral simulation, the 1220 cm( 1)/1070 cm(-1) ratios of diatom samples are sometimes affected by the void effect, but the 950 cm(-1)/800 cm(-1) ratios can indicate real structural information of silica. This void effect should be carefully evaluated for IR micro-spectroscopy of micro-nano-porous materials. Maturity of diatom specimens may be evaluated from: (1) void area percentages determined by SEM; (2) average thicknesses determined by optical microscope; and (3) average values of 1220 cm( 1)/1070 cm(-1) peak height ratios (opposite trend to the void effect) determined by IR micro-spectroscopy. Microscopic heterogeneities of chemical structures of silica were obtained by IR micro-spectroscopic mapping of four representative diatoms. The 950 cm(-1)/800 cm(-1) ratios show that large regions of some diatoms consist of hydrated amorphous immature silica. The successful analysis of diatoms by IR micro-spectroscopic data with careful void effect evaluation may be applied to physicochemical structures of many other bionanomaterials. PMID- 26823544 TI - Preconcentration of Cu(II), Co(II), and Ni(II) using an Optimized Enrichment Procedure: Useful and Alternative Methodology for Flame Atomic Absorption Spectrometry. AB - In this paper, a new solid phase extraction procedure is described for Cu(II), Co(II), and Ni(II). Silica gel which was coated with N,N'-bis(4 methoxysalicylidene) ethylenediamine (MSE) is used as a sorbent. Three independent variables were optimized using central composite design (CCD) for sorption and elution of metal ions. The optimum values of sorption and elution variables allowed simultaneous preconcentration of the ions in same conditions as follows, for sorption, pH 6.9, flow rate 5.4 mL min(-1), sample volume 50.0 mL, and for elution, flow rate 2.6 mL min(-1), eluent concentration 1.0 mol L(-1), eluent volume 5.0 mL. The detection limits (LOD) were found to be 1.1 ug L(-1) for Cu(II), 7.4 ug L(-1) for Co(II), and 7.5 ug L(-1) for Ni(II) and preconcentration factor was 200 for each of the ions. The accuracy of the method was tested with Lake Ontario water and multi-element standard solution. The proposed method was also applied to various water samples. The proposed method can be alternatively suggested as accurate, precise, easy, and a cheap method for Cu(II), Co(II), and Ni(II) determination. PMID- 26823546 TI - A systematic review of the behavioural outcomes following exercise interventions for children and youth with autism spectrum disorder. AB - The purpose of this review was to systematically search and critically analyse the literature pertaining to behavioural outcomes of exercise interventions for individuals with autism spectrum disorder aged ?16 years. This systematic review employed a comprehensive peer-reviewed search strategy, two-stage screening process and rigorous critical appraisal, which resulted in the inclusion of 13 studies. Results demonstrated that exercise interventions consisting individually of jogging, horseback riding, martial arts, swimming or yoga/dance can result in improvements to numerous behavioural outcomes including stereotypic behaviours, social-emotional functioning, cognition and attention. Horseback riding and martial arts interventions may produce the greatest results with moderate to large effect sizes, respectively. Future research with well-controlled designs, standardized assessments, larger sample sizes and longitudinal follow-ups is necessary, in addition to a greater focus on early childhood (aged 0-5 years) and adolescence (aged 12-16 years), to better understand the extent of the behavioural benefits that exercise may provide these populations. PMID- 26823545 TI - GUN1 Controls Accumulation of the Plastid Ribosomal Protein S1 at the Protein Level and Interacts with Proteins Involved in Plastid Protein Homeostasis. AB - Developmental or metabolic changes in chloroplasts can have profound effects on the rest of the plant cell. Such intracellular responses are associated with signals that originate in chloroplasts and convey information on their physiological status to the nucleus, which leads to large-scale changes in gene expression (retrograde signaling). A screen designed to identify components of retrograde signaling resulted in the discovery of the so-called genomes uncoupled (gun) mutants. Genetic evidence suggests that the chloroplast protein GUN1 integrates signals derived from perturbations in plastid redox state, plastid gene expression, and tetrapyrrole biosynthesis (TPB) in Arabidopsis (Arabidopsis thaliana) seedlings, exerting biogenic control of chloroplast functions. However, the molecular mechanism by which GUN1 integrates retrograde signaling in the chloroplast is unclear. Here we show that GUN1 also operates in adult plants, contributing to operational control of chloroplasts. The gun1 mutation genetically interacts with mutations of genes for the chloroplast ribosomal proteins S1 (PRPS1) and L11. Analysis of gun1 prps1 lines indicates that GUN1 controls PRPS1 accumulation at the protein level. The GUN1 protein physically interacts with proteins involved in chloroplast protein homeostasis based on coimmunoprecipitation experiments. Furthermore, yeast two-hybrid and bimolecular fluorescence complementation experiments suggest that GUN1 might transiently interact with several TPB enzymes, including Mg-chelatase subunit D (CHLD) and two other TPB enzymes known to activate retrograde signaling. Moreover, the association of PRPS1 and CHLD with protein complexes is modulated by GUN1. These findings allow us to speculate that retrograde signaling might involve GUN1 dependent formation of protein complexes. PMID- 26823547 TI - The HIV gp41 pocket binding domain enables C-terminal heptad repeat transition from mediating membrane fusion to immune modulation. AB - For successful infection and propagation viruses must overcome many obstacles such as the immune system and entry into their host cells. HIV utilizes its trimeric envelope protein gp160, specifically the gp41 subunit, to enter its host cell. During this process, a gp41-central coiled coil is formed from three N- and three C-terminal heptad repeats, termed the six-helix bundle (SHB), which drives membrane fusion. Recently, T-cell suppression has been reported as an additional function for several regions of gp41 by interfering with the T-cell receptor (TCR) signalling cascade. One of these regions encompasses the conserved pocket binding domain (PBD) that is situated in the C-terminal heptad repeat (CHR) and stabilizes SHB formation. This could indicate that the PBD plays a role in T-cell suppression in addition to its role in membrane fusion. To investigate this dual function, we used two independent cell cultures coupled with biophysical techniques. The data reveal that the PBD mediates T-cell suppression by stabilizing a TCR-binding conformation in the membrane. Moreover, we show that the clinically used HIV fusion inhibitor T-20 did not show suppressive abilities, in contrast with the potent fusion inhibitor C34. In addition, by focusing on SHB conformation after its assembly, we shed light on a mechanism by which gp41's function alternates from membrane fusion facilitation to suppression of TCR activation. PMID- 26823549 TI - Dietary Protein as Kidney Protection: Quality or Quantity? PMID- 26823548 TI - Tubular Epithelial NF-kappaB Activity Regulates Ischemic AKI. AB - NF-kappaB is a key regulator of innate and adaptive immunity and is implicated in the pathogenesis of AKI. The cell type-specific functions of NF-kappaB in the kidney are unknown; however, the pathway serves distinct functions in immune and tissue parenchymal cells. We analyzed tubular epithelial-specific NF-kappaB signaling in a mouse model of ischemia-reperfusion injury (IRI)-induced AKI. NF kappaB reporter activity and nuclear localization of phosphorylated NF-kappaB subunit p65 analyses in mice revealed that IRI induced widespread NF-kappaB activation in renal tubular epithelia and in interstitial cells that peaked 2-3 days after injury. To genetically antagonize tubular epithelial NF-kappaB activity, we generated mice expressing the human NF-kappaB super-repressor IkappaBalphaDeltaN in renal proximal, distal, and collecting duct epithelial cells. Compared with control mice, these mice exhibited improved renal function, reduced tubular apoptosis, and attenuated neutrophil and macrophage infiltration after IRI-induced AKI. Furthermore, tubular NF-kappaB-dependent gene expression profiles revealed temporally distinct functional gene clusters for apoptosis, chemotaxis, and morphogenesis. Primary proximal tubular cells isolated from IkappaBalphaDeltaN-expressing mice and exposed to hypoxia-mimetic agent cobalt chloride exhibited less apoptosis and expressed lower levels of chemokines than cells from control mice did. Our results indicate that postischemic NF-kappaB activation in renal tubular epithelia aggravates tubular injury and exacerbates a maladaptive inflammatory response. PMID- 26823550 TI - Cathepsin D in Podocytes Is Important in the Pathogenesis of Proteinuria and CKD. AB - Studies have revealed many analogies between podocytes and neurons, and these analogies may be key to elucidating the pathogenesis of podocyte injury. Cathepsin D (CD) is a representative aspartic proteinase in lysosomes. Central nervous system neurons in CD-deficient mice exhibit a form of lysosomal storage disease with a phenotype resembling neuronal ceroid lipofuscinoses. In the kidney, the role of CD in podocytes has not been fully explored. Herein, we generated podocyte-specific CD-knockout mice that developed proteinuria at 5 months of age and ESRD by 20-22 months of age. Immunohistochemical analysis of these mice showed apoptotic podocyte death followed by proteinuria and glomerulosclerosis with aging. Using electron microscopy, we identified, in podocytes, granular osmiophilic deposits (GRODs), autophagosome/autolysosome-like bodies, and fingerprint profiles, typical hallmarks of CD-deficient neurons. CD deficiency in podocytes also led to the cessation of autolysosomal degradation and accumulation of proteins indicative of autophagy impairment and the mitochondrial ATP synthase subunit c accumulation in the GRODs, again similar to changes reported in CD-deficient neurons. Furthermore, both podocin and nephrin, two essential components of the slit diaphragm, translocated to Rab7- and lysosome-associated membrane glycoprotein 1-positive amphisomes/autolysosomes that accumulated in podocyte cell bodies in podocyte-specific CD-knockout mice. We hypothesize that defective lysosomal activity resulting in foot process effacement caused this accumulation of podocin and nephrin. Overall, our results suggest that loss of CD in podocytes causes autophagy impairment, triggering the accumulation of toxic subunit c-positive lipofuscins as well as slit diaphragm proteins followed by apoptotic cell death. PMID- 26823551 TI - Impaired Glucose and Insulin Homeostasis in Moderate-Severe CKD. AB - Kidney disease leads to clinically relevant disturbances in glucose and insulin homeostasis, but the pathophysiology in moderate-severe CKD remains incompletely defined. In a cross-sectional study of 59 participants with nondiabetic CKD (mean eGFR =37.6 ml/min per 1.73 m(2)) and 39 healthy control subjects, we quantified insulin sensitivity, clearance, and secretion and glucose tolerance using hyperinsulinemic-euglycemic clamp and intravenous and oral glucose tolerance tests. Participants with CKD had lower insulin sensitivity than participants without CKD (mean[SD] 3.9[2.0] versus 5.0 [2.0] mg/min per uU/ml; P<0.01). Insulin clearance correlated with insulin sensitivity (r=0.72; P<0.001) and was also lower in participants with CKD than controls (876 [226] versus 998 [212] ml/min; P<0.01). Adjustment for physical activity, diet, fat mass, and fatfree mass in addition to demographics and smoking partially attenuated associations of CKD with insulin sensitivity (adjusted difference, -0.7; 95% confidence interval, -1.4 to 0.0 mg/min per uU/ml) and insulin clearance (adjusted difference, -85; 95% confidence interval, -160 to -10 ml/min). Among participants with CKD, eGFR did not significantly correlate with insulin sensitivity or clearance. Insulin secretion and glucose tolerance did not differ significantly between groups, but 65% of participants with CKD had impaired glucose tolerance. In conclusion, moderate-severe CKD associated with reductions in insulin sensitivity and clearance that are explained, in part, by differences in lifestyle and body composition. We did not observe a CKD-specific deficit in insulin secretion, but the combination of insulin resistance and inadequate augmentation of insulin secretion led to a high prevalence of impaired glucose tolerance. PMID- 26823552 TI - Ketoanalogue-Supplemented Vegetarian Very Low-Protein Diet and CKD Progression. AB - Dietary protein restriction may improve determinants of CKD progression. However, the extent of improvement and effect of ketoanalogue supplementation are unclear. We conducted a prospective, randomized, controlled trial of safety and efficacy of ketoanalogue-supplemented vegetarian very low-protein diet (KD) compared with conventional low-protein diet (LPD). Primary end point was RRT initiation or >50% reduction in initial eGFR. Nondiabetic adults with stable eGFR<30 ml/min per 1.73 m(2), proteinuria <1 g/g urinary creatinine, good nutritional status, and good diet compliance entered a run-in phase on LPD. After 3 months, compliant patients were randomized to KD (0.3 g/kg vegetable proteins and 1 cps/5 kg ketoanalogues per day) or continue LPD (0.6 g/kg per day) for 15 months. Only 14% of screened patients patients were randomized, with no differences between groups. Adjusted numbers needed to treat (NNTs; 95% confidence interval) to avoid composite primary end point in intention to treat and per-protocol analyses in one patient were 4.4 (4.2 to 5.1) and 4.0 (3.9 to 4.4), respectively, for patients with eGFR<30 ml/min per 1.73 m(2) Adjusted NNT (95% confidence interval) to avoid dialysis was 22.4 (21.5 to 25.1) for patients with eGFR<30 ml/min per 1.73 m(2) but decreased to 2.7 (2.6 to 3.1) for patients with eGFR<20 ml/min per 1.73 m(2) in intention to treat analysis. Correction of metabolic abnormalities occurred only with KD. Compliance to diet was good, with no changes in nutritional parameters and no adverse reactions. Thus, this KD seems nutritionally safe and could defer dialysis initiation in some patients with CKD. PMID- 26823553 TI - Predicted Mutation Strength of Nontruncating PKD1 Mutations Aids Genotype Phenotype Correlations in Autosomal Dominant Polycystic Kidney Disease. AB - Autosomal dominant polycystic kidney disease (ADPKD) often results in ESRD but with a highly variable course. Mutations to PKD1 or PKD2 cause ADPKD; both loci have high levels of allelic heterogeneity. We evaluated genotype-phenotype correlations in 1119 patients (945 families) from the HALT Progression of PKD Study and the Consortium of Radiologic Imaging Study of PKD Study. The population was defined as: 77.7% PKD1, 14.7% PKD2, and 7.6% with no mutation detected (NMD). Phenotypic end points were sex, eGFR, height-adjusted total kidney volume (htTKV), and liver cyst volume. Analysis of the eGFR and htTKV measures showed that the PKD1 group had more severe disease than the PKD2 group, whereas the NMD group had a PKD2-like phenotype. In both the PKD1 and PKD2 populations, men had more severe renal disease, but women had larger liver cyst volumes. Compared with nontruncating PKD1 mutations, truncating PKD1 mutations associated with lower eGFR, but the mutation groups were not differentiated by htTKV. PKD1 nontruncating mutations were evaluated for conservation and chemical change and subdivided into strong (mutation strength group 2 [MSG2]) and weak (MSG3) mutation groups. Analysis of eGFR and htTKV measures showed that patients with MSG3 but not MSG2 mutations had significantly milder disease than patients with truncating cases (MSG1), an association especially evident in extreme decile populations. Overall, we have quantified the contribution of genic and PKD1 allelic effects and sex to the ADPKD phenotype. Intrafamilial correlation analysis showed that other factors shared by families influence htTKV, with these additional genetic/environmental factors significantly affecting the ADPKD phenotype. PMID- 26823554 TI - The Risk of Major Hemorrhage with CKD. AB - New staging systems for CKD account for both reduced eGFR and albuminuria; whether each measure associates with greater risk of hemorrhage is unclear. In this retrospective cohort study (2002-2010), we grouped 516,197 adults >=40 years old by eGFR (>=90, 60 to <90, 45 to <60, 30 to <45, 15 to <30, or <15 ml/min per 1.73 m(2)) and urine albumin-to-creatinine ratio (ACR; >300, 30-300, or <30 mg/g) to examine incidence of hemorrhage. The 3-year cumulative incidence of hemorrhage increased 20-fold across declining eGFR and increasing urine ACR groupings (highest eGFR/lowest ACR: 0.5%; lowest eGFR/highest ACR: 10.1%). Urine ACR altered the association of eGFR with hemorrhage (P<0.001). In adjusted models using the highest eGFR/lowest ACR grouping as the referent, patients with eGFR=15 to <30 ml/min per 1.73 m(2) had adjusted relative risks of hemorrhage of 1.9 (95% confidence interval [95% CI], 1.5 to 2.4) with the lowest ACR and 3.7 (95% CI, 3.0 to 4.5) with the highest ACR. Patients with the highest eGFR/highest ACR had an adjusted relative risk of hemorrhage of 2.3 (95% CI, 1.8 to 2.9), comparable with the risk for patients with the lowest eGFR/lowest ACR. The associations attenuated but remained significant after adjustment for anticoagulant and antiplatelet use in patients >=66 years old. The risk of hemorrhage differed by urine ACR in high risk subgroups. Our data show that declining eGFR and increasing albuminuria each independently increase hemorrhage risk. Strategies to reduce hemorrhage events among patients with CKD are warranted. PMID- 26823556 TI - The utility of radioisotope cisternography in low CSF/volume syndromes compared to myelography. AB - Objective The objective of this report is to compare computed tomography (CT) and magnetic resonance (MR) myelography with radioisotope cisternography (RC) for detection of spinal cerebrospinal (CSF) leaks. Methods We retrospectively reviewed 12 spontaneous intracranial hypotension (SIH) patients; CT and RC were performed simultaneously. Three patients had MR myelography. Results CT and/or MR myelography identified CSF leaks in four of 12 patients. RC detected spinal leaks in all three patients confirmed by CT myelography; RC identified the CSF leak location in two of three cases, and these were due to osteophytic spicules and/or discs. RC showed only enlarged perineural activity. Only intrathecal gadolinium MR myelography clearly identified a slow leak from a perineural cyst. In eight remaining cases, the leak site was unknown; however, two of these showed indirect signs of CSF leak on RC. CSF slow leaks from perineural cysts were the most common presumed etiology; and the cysts were best visualized on myelography. Conclusion RC is comparable to CT myelography but has spatial limitations and should be limited to atypical cases. PMID- 26823555 TI - A Novel Extrinsic Pathway for the Unfolded Protein Response in the Kidney. AB - The ribonuclease angiogenin is a component of the mammalian stress response, and functions in both cell-autonomous and non-cell-autonomous ways to promote tissue adaptation to injury. We recently showed that angiogenin regulates tissue homeostasis during AKI associated with endoplasmic reticulum (ER) stress through the production of transfer RNA fragments that interfere with translation initiation and thereby alleviate ER stress. However, whether the paracrine signaling mediated by angiogenin secretion is a genuine component of the ER stress response to kidney injury is unknown. Here, we explored the molecular mechanisms by which angiogenin is secreted upon ER stress, and determined how it modulates the inflammatory microenvironment. In cultured renal epithelial cells, ER stress specifically induced angiogenin secretion under the selective control of inositol-requiring enzyme 1alpha, a key activator of the unfolded protein response. The transcription factors spliced X-box-binding protein 1 and p65, which are activated by inositol-requiring enzyme 1alpha upon ER stress, each bound the angiogenin promoter and controlled the amount of angiogenin secreted. Furthermore, p65 promoted angiogenin transcription in an ER stress-dependent manner. Similar to secretion of the ER stress-induced proinflammatory cytokine IL 6, secretion of angiogenin required the ER-Golgi pathway. Notably, incubation of human macrophages with angiogenin promoted macrophage reprogramming toward an activated and proinflammatory phenotype. In patients, angiogenin expression increased upon renal inflammation, and the urinary concentration of angiogenin correlated with the extent of immune-mediated kidney injury. Collectively, our data identify angiogenin as a mediator of the ER stress-dependent inflammatory response and as a potential noninvasive biomarker of AKI. PMID- 26823557 TI - A Healthy Weight for Toddlers? Two-Year Follow-up of a Randomized Controlled Trial of Group Well-Child Care. PMID- 26823558 TI - Gender difference in plasma fatty-acid-binding protein 4 levels in patients with chronic obstructive pulmonary disease. AB - COPD (chronic obstructive pulmonary disease) is characterized by airway inflammation and increases the likelihood of the development of atherosclerosis. Recent studies have indicated that FABP4 (fatty-acid-binding protein 4), an intracellular lipid chaperone of low molecular mass, plays an important role in the regulation of inflammation and atherosclerosis. We carried out a preliminary clinical study aiming at investigating the relationships between circulating FABP4 levels in patients with COPD and inflammation and lung function. We enrolled 50 COPD patients and 39 healthy controls in the study. Lung function tests were performed in all subjects. Plasma levels of FABP4 and adiponectin, TNFalpha (tumour necrosis factor alpha) and CRP (C-reactive protein) were measured. The correlations between FABP4 and lung function, adipokine (adiponectin), inflammatory factors and BMI (body mass index) were analysed. Compared with both males with COPD and healthy females, plasma FABP4 levels in females with COPD were significantly increased. Adiponectin and CRP levels were significantly higher in patients with COPD. Furthermore, we found that FABP4 levels were inversely correlated with FEV1% predicted (FEV1 is forced expiratory volume in 1 s) and positively correlated with adiponectin and TNFalpha in COPD patients. In addition, a positive correlation between plasma FABP4 and CRP was found in females with COPD. However, FABP4 levels were not correlated with BMI. Our results underline a gender difference in FABP4 secretion in stable COPD patients. Further studies are warranted to clarify the exact role of FABP4 in the pathogenesis of COPD. PMID- 26823560 TI - EEF1D modulates proliferation and epithelial-mesenchymal transition in oral squamous cell carcinoma. AB - EEF1D (eukaryotic translation elongation factor 1delta) is a subunit of the elongation factor 1 complex of proteins that mediates the elongation process during protein synthesis via enzymatic delivery of aminoacyl-tRNAs to the ribosome. Although the functions of EEF1D in the translation process are recognized, EEF1D expression was found to be unbalanced in tumours. In the present study, we demonstrate the overexpression of EEF1D in OSCC (oral squamous cell carcinoma), and revealed that EEF1D and protein interaction partners promote the activation of cyclin D1 and vimentin proteins. EEF1D knockdown in OSCC reduced cell proliferation and induced EMT (epithelial-mesenchymal transition) phenotypes, including cell invasion. Taken together, these results define EEF1D as a critical inducer of OSCC proliferation and EMT. PMID- 26823559 TI - Unravelling the complex drug-drug interactions of the cardiovascular drugs, verapamil and digoxin, with P-glycoprotein. AB - Drug-drug interactions (DDIs) and associated toxicity from cardiovascular drugs represents a major problem for effective co-administration of cardiovascular therapeutics. A significant amount of drug toxicity from DDIs occurs because of drug interactions and multiple cardiovascular drug binding to the efflux transporter P-glycoprotein (Pgp), which is particularly problematic for cardiovascular drugs because of their relatively low therapeutic indexes. The calcium channel antagonist, verapamil and the cardiac glycoside, digoxin, exhibit DDIs with Pgp through non-competitive inhibition of digoxin transport, which leads to elevated digoxin plasma concentrations and digoxin toxicity. In the present study, verapamil-induced ATPase activation kinetics were biphasic implying at least two verapamil-binding sites on Pgp, whereas monophasic digoxin activation of Pgp-coupled ATPase kinetics suggested a single digoxin-binding site. Using intrinsic protein fluorescence and the saturation transfer double difference (STDD) NMR techniques to probe drug-Pgp interactions, verapamil was found to have little effect on digoxin-Pgp interactions at low concentrations of verapamil, which is consistent with simultaneous binding of the drugs and non competitive inhibition. Higher concentrations of verapamil caused significant disruption of digoxin-Pgp interactions that suggested overlapping and competing drug-binding sites. These interactions correlated to drug-induced conformational changes deduced from acrylamide quenching of Pgp tryptophan fluorescence. Also, Pgp-coupled ATPase activity kinetics measured with a range of verapamil and digoxin concentrations fit well to a DDI model encompassing non-competitive and competitive inhibition of digoxin by verapamil. The results and previous transport studies were combined into a comprehensive model of verapamil-digoxin DDIs encompassing drug binding, ATP hydrolysis, transport and conformational changes. PMID- 26823561 TI - Impact of Training Method on the Robustness of the Visual Assessment of 18F Florbetaben PET Scans: Results from a Phase-3 Study. AB - Training for accurate image interpretation is essential for the clinical use of beta-amyloid PET imaging, but the role of interpreter training and the accuracy of the algorithm for routine visual assessment of florbetaben PET scans are unclear. The aim of this study was to test the robustness of the visual assessment method for florbetaben scans, comparing efficacy readouts across different interpreters and training methods and against a histopathology standard of truth (SoT). METHODS: Analysis was based on data from an international open label, nonrandomized, multicenter phase-3 study in patients with or without dementia (ClinicalTrials.gov: NCT01020838). Florbetaben scans were assessed visually and quantitatively, and results were compared with amyloid plaque scores. For visual assessment, either in-person training (n = 3 expert interpreters) or an electronic training method (n = 5 naive interpreters) was used. Brain samples from participants who died during the study were used to determine the histopathologic SoT using Bielschowsky silver staining (BSS) and immunohistochemistry for beta-amyloid plaques. RESULTS: Data were available from 82 patients who died and underwent postmortem histopathology. When visual assessment results were compared with BSS + immunohistochemistry as SoT, median sensitivity was 98.2% for the in-person-trained interpreters and 96.4% for the e trained interpreters, and median specificity was 92.3% and 88.5%, respectively. Median accuracy was 95.1% and 91.5%, respectively. On the basis of BSS only as the SoT, median sensitivity was 98.1% and 96.2%, respectively; median specificity was 80.0% and 76.7%, respectively; and median accuracy was 91.5% and 86.6%, respectively. Interinterpreter agreement (Fleiss kappa) was excellent (0.89) for in-person-trained interpreters and very good (0.71) for e-trained interpreters. Median intrainterpreter agreement was 0.9 for both in-person-trained and e trained interpreters. Visual and quantitative assessments were concordant in 88.9% of scans for in-person-trained interpreters and in 87.7% of scans for e trained interpreters. CONCLUSION: Visual assessment of florbetaben images was robust in challenging scans from elderly end-of-life individuals. Sensitivity, specificity, and interinterpreter agreement were high, independent of expertise and training method. Visual assessment was accurate and reliable for detection of plaques using BSS and immunohistochemistry and well correlated with quantitative assessments. PMID- 26823563 TI - Emerging Opportunities for c-MET Visualization in the Clinic. PMID- 26823562 TI - Impact of MR-Based Attenuation Correction on Neurologic PET Studies. AB - Hybrid PET and MR scanners have become a reality in recent years, with the benefits of reduced radiation exposure, reduction of imaging time, and potential advantages in quantification. Appropriate attenuation correction remains a challenge. Biases in PET activity measurements were demonstrated using the current MR-based attenuation-correction technique. We aimed to investigate the impact of using a standard MR-based attenuation correction technique on the clinical and research utility of a PET/MR hybrid scanner for amyloid imaging. METHODS: Florbetapir scans were obtained for 40 participants on a hybrid scanner with simultaneous MR acquisition. PET images were reconstructed using both MR- and CT-derived attenuation maps. Quantitative analysis was performed for both datasets to assess the impact of MR-based attenuation correction to absolute PET activity measurements as well as target-to-reference ratio (SUVR). Clinical assessment was also performed by a nuclear medicine physician to determine amyloid status based on the criteria in the Food and Drug Administration prescribing information for florbetapir. RESULTS: MR-based attenuation correction led to underestimation of PET activity for most parts of the brain, with a small overestimation for deep brain regions. There was also an overestimation of SUVRs with cerebellar reference. SUVR measurements obtained from the 2 attenuation correction methods were strongly correlated. Clinical assessment of amyloid status resulted in identical classification as positive or negative regardless of the attenuation-correction methods. CONCLUSION: MR-based attenuation correction causes biases in quantitative measurements. The biases may be accounted for by a linear model, although the spatial variation cannot be easily modeled. The quantitative differences, however, did not affect clinical assessment as positive or negative. PMID- 26823564 TI - High Diagnostic Value of 18F-FDG PET/CT in Endometrial Cancer: Systematic Review and Meta-Analysis of the Literature. AB - The aim of this study was to evaluate the diagnostic performance of (18)F-FDG PET/CT for the preoperative assessment of lymph node metastases (LNM) in endometrial cancer patients and for the assessment of endometrial cancer recurrence (ECR) after primary surgical treatment. METHODS: A comprehensive search was performed on Pubmed/MEDLINE databases for studies reporting the diagnostic performance of (18)F-FDG PET/CT for assessment of LNM and ECR published up to August 15, 2015. Twenty-one studies (13 for LNM and 8 for ECR) were included in the systematic review and meta-analysis. Pooled estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of the (18)F-FDG PET/CT were calculated along with 95% confidence intervals (CIs). A summary receiver-operating-characteristics curve (SROC) was constructed, and the area under the SROC curve (AUC) was determined along with Q* index. RESULTS: The overall pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and AUC (with 95% CI) of (18)F-FDG PET/CT for detection of LNM were 0.72 (95% CI, 0.63-0.80), 0.94 (95% CI, 0.93-0.96), 10.9 (95% CI, 7.9-15.1), 0.36 (95% CI, 0.27 0.48), 39.7 (95% CI, 21.4-73.6), and 0.94 (95% CI, 0.85-0.99), respectively, whereas the corresponding numbers for detection of ECR were 0.95 (95% CI, 0.91 0.98), 0.91 (95% CI, 0.86-0.94), 8.8 (95% CI, 6.0-12.7), 0.08 (95% CI, 0.05 0.15), 171.7 (95% CI, 67.9-434.3), and 0.97 (95% CI, 0.95-0.98), respectively. The overall diagnostic accuracy (Q* index) in LNM and ECR were 0.88 and 0.93, respectively. CONCLUSION: (18)F-FDG PET/CT has an excellent diagnostic performance for detecting LNM preoperatively and disease recurrence postoperatively in endometrial cancer patients. PMID- 26823565 TI - Effect of Attenuation Correction on Regional Quantification Between PET/MR and PET/CT: A Multicenter Study Using a 3-Dimensional Brain Phantom. AB - A spatial bias in brain PET/MR exists compared with PET/CT, because of MR-based attenuation correction. We performed an evaluation among 4 institutions, 3 PET/MR systems, and 4 PET/CT systems using an anthropomorphic brain phantom, hypothesizing that the spatial bias would be minimized with CT-based attenuation correction (CTAC). METHODS: The evaluation protocol was similar to the quantification of changes in neurologic PET studies. Regional analysis was conducted on 8 anatomic volumes of interest (VOIs) in gray matter on count normalized, resolution-matched, coregistered data. On PET/MR systems, CTAC was applied as the reference method for attenuation correction. RESULTS: With CTAC, visual and quantitative differences between PET/MR and PET/CT systems were minimized. Intersystem variation between institutions was +3.42% to -3.29% in all VOIs for PET/CT and +2.15% to -4.50% in all VOIs for PET/MR. PET/MR systems differed by +2.34% to -2.21%, +2.04% to -2.08%, and -1.77% to -5.37% when compared with a PET/CT system at each institution, and these differences were not significant (P >= 0.05). CONCLUSION: Visual and quantitative differences between PET/MR and PET/CT systems can be minimized by an accurate and standardized method of attenuation correction. If a method similar to CTAC can be implemented for brain PET/MRI, there is no reason why PET/MR should not perform as well as PET/CT. PMID- 26823566 TI - 18F-FDG PET/CT of Non-Small Cell Lung Carcinoma Under Neoadjuvant Chemotherapy: Background-Based Adaptive-Volume Metrics Outperform TLG and MTV in Predicting Histopathologic Response. AB - Assessment of tumor response after chemotherapy using (18)F-FDG PET metrics is gaining acceptance. Several studies have suggested that the parameters metabolically active tumor volume (MTV) and total lesion glycolysis (TLG) are superior to SUVmax for measuring tumor burden. However, the measurement of MTV and TLG is still controversial; the most common method uses an absolute threshold of 42% of SUVmax Recently, we implemented a background-adaptive method to determine the background-subtracted lesion activity (BSL) and the background subtracted volume (BSV). In this study, we investigated the correlation between such PET metrics and histopathologic response in non-small cell lung carcinoma (NSCLC). METHODS: Forty-four NSCLC patients were retrospectively identified. Their PET/CT data on both types of scan before and after neoadjuvant chemotherapy were analyzed regarding SUVmax, MTV, TLG, BSL, and BSV, as well as the relative changes in these parameters. The tumor regression score as an indicator of histopathologic response was scored on hematoxylin- and eosin-stained sections of the surgical specimens using a 4-tiered scale (scores 1-4). The correlation between score and the absolute and relative PET metrics after chemotherapy was analyzed using Spearman rank correlation tests. RESULTS: Tumors that demonstrated a good response after neoadjuvant chemotherapy had significantly lower (18)F-FDG activity than nonresponding tumors (scores 3 and 4: SUVmax, 4.2 [range, 1.8-7.9] vs. scores 1 and 2: SUVmax, 8.1 [range, 1.4-40.4]; P = 0.001). The same was found for change in SUVmax and score (P = 0.001). PET volume metrics based on a 42% fixed threshold for SUVmax did not correlate with score (TLG, P = 0.505; MTV, P = 0.386). However, both of the background activity-based PET volume metrics-BSL and BSV-significantly correlated with score (P < 0.001 each). CONCLUSION: PET volume metrics based on background-adaptive methods correlate better with histopathologic tumor regression score in NSCLC patients under neoadjuvant chemotherapy than algorithms and methods using a fixed threshold (42% SUVmax). PMID- 26823567 TI - Pharmacokinetic Analysis of 11C-PBR28 in the Rat Model of Herpes Encephalitis: Comparison with (R)-11C-PK11195. AB - (11)C-PBR28 is a second-generation translocator protein (TSPO) tracer with characteristics supposedly superior to the most commonly used tracer for neuroinflammation, (R)-(11)C-PK11195. Despite its use in clinical research, no studies on the imaging properties and pharmacokinetic analysis of (11)C-PBR28 in rodent models of neuroinflammation have been published yet. Therefore, this study aimed to evaluate (11)C-PBR28 as a tool for detection and quantification of neuroinflammation in preclinical research and to compare its imaging properties with (R)-(11)C-PK11195. The herpes simplex encephalitis (HSE) model was used for induction of neuroinflammation in male Wistar rats. Six or 7 d after virus inoculation, a dynamic (11)C-PBR28 or (R)-(11)C-PK11195 PET scan with arterial blood sampling was obtained. Pharmacokinetic modeling was performed on the PET data and analyzed using volumes of interest and a voxel-based approach. Volume-of interest- and voxel-based analysis of (11)C-PBR28 images showed overexpression of TSPO in brain regions known to be affected in the HSE rat model. (11)C-PBR28 was metabolized faster than (R)-(11)C-PK11195, with a metabolic half-life in plasma of 5 and 21 min, respectively. Overall, (11)C-PBR28 was more sensitive than (R) (11)C-PK11195 in detecting neuroinflammation. The binding potential (BPND) of (11)C-PBR28 was significantly higher (P < 0.05) in the medulla (176%), pons (146%), midbrain (101%), hippocampus (85%), thalamus (73%), cerebellum (54%), and hypothalamus (49%) in HSE rats than in control rats, whereas (R)-(11)C-PK11195 showed a higher BPND only in the medulla (32%). The BPND in control animals was not significantly different between tracers, suggesting that the nonspecific binding of both tracers is similar. (11)C-PBR28 was more sensitive than (R)-(11)C PK11195 in the detection of TSPO overexpression in the HSE rat model, because more brain regions with significantly increased tracer uptake could be found, irrespective of the data analysis method used. These results suggest that (11)C PBR28 should be able to detect more subtle changes in microglial activation in preclinical models of neuroinflammation. PMID- 26823569 TI - Breast-Specific gamma-Imaging for the Detection of Mammographically Occult Breast Cancer in Women at Increased Risk. AB - Breast-specific gamma-imaging (BSGI) is a physiologic imaging modality that can detect subcentimeter and mammographically occult breast cancer, with a sensitivity and specificity comparable to MRI. The purpose of this study was to determine the incremental increase in breast cancer detection when BSGI is used as an adjunct to mammography in women at increased risk for breast cancer. METHODS: All patients undergoing BSGI from April 2010 through January 2014 were retrospectively reviewed. Eligible patients were identified as women at increased risk for breast cancer and whose most recent mammogram was benign. Examinations exhibiting focally increased radiotracer uptake were considered positive. Incremental increase in cancer detection was calculated as the percentage of mammographically occult BSGI-detected breast cancer and the number of mammographically occult breast cancers detected per 1,000 women screened. RESULTS: Included in this study were 849 patients in whom 14 BSGI examinations detected mammographically occult breast cancer. Patients ranged in age from 26 to 83 y, with a mean age of 57 y. Eleven of 14 cancers were detected in women with dense breasts. The addition of BSGI to the annual breast screen of asymptomatic women at increased risk for breast cancer yields 16.5 cancers per 1,000 women screened. When high-risk lesions and cancers were combined, BSGI detected 33.0 high-risk lesions and cancers per 1,000 women screened. CONCLUSION: BSGI is a reliable adjunct modality to screening mammography that increases breast cancer detection by 1.7% (14/849) in women at increased risk for breast cancer, comparable to results reported for breast MRI. BSGI is beneficial in breast cancer detection in women at increased risk, particularly in those with dense breasts. PMID- 26823570 TI - Complete Genome Sequence Analysis of Acute and Mild Strains of Classical Swine Fever Virus Subgenotype 3.2. AB - We report the complete genome sequences of two classical swine fever virus strains (JJ9811 and YI9908). Both belong to subgenotype 3.2. Strain JJ9811 causes mild symptoms and strain YI9908 causes acute symptoms. The sequences were 95.7% homologous at the nucleotide level and 95.6% homologous at the amino acid level. PMID- 26823568 TI - Radiation Dosimetry of Whole-Body Dual-Tracer 18F-FDG and 11C-Acetate PET/CT for Hepatocellular Carcinoma. AB - Combined whole-body dual-tracer ((18)F-FDG and (11)C-acetate) PET/CT is increasingly used for staging hepatocellular carcinoma, with only limited studies investigating the radiation dosimetry data of these scans. The aim of the study was to characterize the radiation dosimetry of combined whole-body dual-tracer PET/CT protocols. METHODS: Consecutive adult patients with hepatocellular carcinoma who underwent whole-body dual-tracer PET/CT scans were retrospectively reviewed with institutional review board approval. OLINDA/EXM 1.1 was used to estimate patient-specific internal dose exposure in each organ. Biokinetic models for (18)F-FDG and (11)C-acetate as provided by ICRP (International Commission on Radiological Protection) publication 106 were used. Standard reference phantoms were modified to more closely represent patient-specific organ mass. With patient specific parameters, organ equivalent doses from each CT series were estimated using VirtualDose. Dosimetry capabilities for tube current modulation protocols were applied by integrating with the latest anatomic realistic models. Effective dose was calculated using ICRP publication 103 tissue-weighting coefficients for adult male and female, respectively. RESULTS: Fourteen scans were evaluated (12 men, 2 women; mean age +/- SD, 60 +/- 19.48 y). The patient-specific effective dose from (18)F-FDG and (11)C-acetate was 6.08 +/- 1.49 and 1.56 +/- 0.47 mSv, respectively, for male patients and 6.62 +/- 1.38 and 1.79 +/- 0.12 mSV, respectively, for female patients. The patient-specific effective dose of the CT component, which comprised 2 noncontrast whole-body scans, to male and female patients was 21.20 +/- 8.94 and 14.79 +/- 3.35 mSv, respectively. Thus, the total effective doses of the combined whole-body dual-tracer PET/CT studies for male and female patients were 28.84 +/- 10.18 and 23.19 +/- 4.61 mSv, respectively. CONCLUSION: Patient-specific parameters allow for more accurate estimation of organ equivalent doses. Considering the substantial radiation dose incurred, judicious medical justification is required with every whole-body dual-tracer PET/CT referral. Although radiation risks may have less impact for the population with cancer because of their reduced life expectancy, the information is of interest and relevant for both justification, to evaluate risk/benefit, and protocol optimization. PMID- 26823571 TI - Complete Genome Sequence and Methylome of Salmonella enterica subsp. enterica Cerro, a Frequent Dairy Cow Serovar. AB - Salmonella enterica subsp. enterica serovar Cerro is an infrequent pathogen of humans and other mammals but is frequently isolated from the hindgut of asymptomatic cattle in the United States. To further understand the genomic determinants of S. Cerro specificity for the bovine hindgut, the genome of isolate CFSAN001588 was fully sequenced and deposited in the GenBank database. PMID- 26823572 TI - Draft Genome Sequences of Nine Strains of Ralstonia solanacearum Differing in Virulence to Eggplant (Solanum melongena). AB - Ralstonia solanacearum displays variability in its virulence to solanaceous crops. We report here the draft genome sequences of eight phylotype I strains and one phylotype III strain differing in virulence to the resistant eggplant genotype AG91-25. These data will allow the identification of virulence- and avirulence-related genes. PMID- 26823573 TI - Genome Sequence of Janthinobacterium sp. CG23_2, a Violacein-Producing Isolate from an Antarctic Supraglacial Stream. AB - Here, we present the draft genome sequence for the violacein-producing Janthinobacterium sp. CG23_2 isolated from an Antarctic supraglacial stream. The genome is ~7.85 Mb, with a G+C content of 63.5%. The genome includes 7,247 candidate protein coding genes, which may provide insight into UV tolerance mechanisms. PMID- 26823574 TI - Draft Genome Sequences of Five Pseudomonas aeruginosa Clinical Strains Isolated from Sputum Samples from Cystic Fibrosis Patients. AB - We report here the draft genome sequences of five Pseudomonas aeruginosa isolates obtained from sputum samples from two cystic fibrosis patients with chronic colonization. These closely related strains harbor 225 to 493 genes absent from the P. aeruginosa POA1 genome and contain 178 to 179 virulence factors and 29 to 31 antibiotic resistance genes. PMID- 26823575 TI - Draft Genome Assembly of a Filamentous Euendolithic (True Boring) Cyanobacterium, Mastigocoleus testarum Strain BC008. AB - Mastigocoleus testarum strain BC008 is a model organism used to study marine photoautotrophic carbonate dissolution. It is a multicellular, filamentous, diazotrophic, euendolithic cyanobacterium ubiquitously found in marine benthic environments. We present an accurate draft genome assembly of 172 contigs spanning 12,700,239 bp with 9,131 annotated genes with an average G+C% of 37.3. PMID- 26823576 TI - Identification and Complete Genome Sequence Analysis of a Genotype XIV Newcastle Disease Virus from Nigeria. AB - The first complete genome sequence of a strain of Newcastle disease virus (NDV) from genotype XIV is reported here. Strain duck/Nigeria/NG-695/KG.LOM.11-16/2009 was isolated from an apparently healthy domestic duck from a live bird market in Kogi State, Nigeria, in 2009. This strain is classified as a member of subgenotype XIVb of class II. PMID- 26823577 TI - Complete Genome Sequence of Rehmannia Mosaic Virus Infecting Rehmannia glutinosa in South Korea. AB - The complete genome sequence of a South Korean isolate of Rehmannia mosaic virus (ReMV) infecting Rehmannia glutinosa was determined through next-generation sequencing and Sanger sequencing. To our knowledge, this is the first report of a natural infection of R. glutinosa by ReMV in South Korea. PMID- 26823578 TI - Complete Genomic Sequence of an Avian Pathogenic Escherichia coli Strain of Serotype O7:HNT. AB - Avian pathogenic Escherichia coli (APEC) is associated with colibacillosis in poultry. Here, we present the first complete sequence of an APEC strain of the O7:HNT serotype and ST73 sequence type, isolated from a broiler with cellulitis. Complete genomes of APEC with distinct genetic backgrounds may be useful for comparative analysis. PMID- 26823579 TI - Complete Genome Sequence of Nonhemolytic Streptococcus agalactiae Serotype V Strain 1, Isolated from the Buccal Cavity of a Canine. AB - The complete genome sequence from a nonhemolytic strain of Streptococcus agalactiae from the oral cavity of a canine was assembled. The genome is 2,165,968 bp, contains 2,055 genes, and is classified as group B streptococcus (GBS) serotype V, strain 1. A comparison to other S. agalactiae sequences shows high gene synteny with human and bovine strains. PMID- 26823580 TI - Complete Genome Sequence of Fish Pathogen Aeromonas hydrophila JBN2301. AB - Aeromonas hydrophila is one of the most important fish pathogens in China. Here, we report complete genome sequence of a virulent strain, A. hydrophila JBN2301, which was isolated from diseased crucian carp. PMID- 26823581 TI - Draft Genome Sequence of Probiotic Enterococcus faecium Strain L-3. AB - We report here the draft genome sequence of the bacteriocin producer Enterococcus faecium strain L-3, isolated from a probiotic preparation, Laminolact, which is widely used in the Russian Federation. The draft genome sequence is composed of 74 contigs for a total of 2,643,001 bp, with 2,646 coding genes. Five clusters for bacteriocin production were found. PMID- 26823582 TI - Complete Genome Sequence of Pseudomonas brassicacearum LBUM300, a Disease Suppressive Bacterium with Antagonistic Activity toward Fungal, Oomycete, and Bacterial Plant Pathogens. AB - Pseudomonas brassicacearum LBUM300, a plant rhizosphere-inhabiting bacterium, produces 2,4-diacetylphloroglucinol and hydrogen cyanide and has shown antagonistic activity against the plant pathogens Verticillium dahliae, Phytophthora cactorum, and Clavibacter michiganensis subsp. michiganensis. Here, we report the complete genome sequence of P. brassicacearum LBUM300. PMID- 26823583 TI - Complete Genome Sequence of Porcine Parvovirus 2 Recovered from Swine Sera. AB - A complete genomic sequence of porcine parvovirus 2 (PPV-2) was detected by viral metagenome analysis on swine sera. A phylogenetic analysis of this genome reveals that it is highly similar to previously reported North American PPV-2 genomes. The complete PPV-2 sequence is 5,426 nucleotides long. PMID- 26823584 TI - Draft Genome Sequence of Klebsiella pneumoniae KGM-IMP216 Harboring blaCTX-M-15, blaDHA-1, blaTEM-1B, blaNDM-1, blaSHV-28, and blaOXA-1, Isolated from a Patient in Lebanon. AB - We present the draft genome of highly drug-resistant Klebsiella pneumoniae KGM IMP216, isolated from a urine sample collected from a patient in Lebanon. The draft genome sequence consisted of 77 contigs, including a combined 5,731,500 bases with 57% G+C content. PMID- 26823585 TI - Complete Genome Sequence of the Proteorhodopsin-Containing Marine Bacterium Sediminicola sp. YIK13. AB - Sediminicola sp. YIK13 is a marine flavobacterium, isolated from tidal flat sediment. Here, we present the first complete genome sequence of this genus, which consists of 3,569,807 bp with 39.4% GC content. This strain contains proteorhodopsin, as well as retinal biosynthesis genes, allowing it to utilize sunlight as an energy source. PMID- 26823586 TI - Complete Genome Sequence of the Exopolysaccharide-Producing Burkholderia caribensis Type Strain MWAP64. AB - We report the complete genome sequence of Burkholderia caribensis MWAP64 (LMG 18531), which was isolated from soil for its proficiency in producing large amounts of exopolysaccharide that help form microaggregates in a vertisol. There are four replicons with a total size of 9,032,119 bp. PMID- 26823587 TI - Complete Genome Sequence of Novel Pseudorabies Virus Strain HNB Isolated in China. AB - The complete genome sequence of a novel pseudorabies virus, strain HNB, isolated from a dead weaned pig in China, was determined using next-generation sequencing. The viral genome sequence of HNB shared 90.6% nucleotide similarity with that of the traditional vaccine strain, the Bartha strain. PMID- 26823588 TI - Genome Sequences of Five Arboviruses in Field-Captured Mosquitoes in a Unique Rural Environment of South Korea. AB - Here, we present the genome sequences of one mesonivirus and four novel arboviruses observed in Culex bitaeniorhynchus and Culex pipiens, captured in and near the demilitarized zone, Republic of Korea. Results suggest the ubiquitous presence of mesoniviruses and the discovery of a potentially new species of arboviruses in field-captured mosquitoes. PMID- 26823589 TI - Complete Genome Sequence of Human Norovirus GII.4_2006b, a Variant of Minerva 2006. AB - In 2006, the National Calicivirus Laboratory at the U.S. Centers for Disease Control and Prevention (CDC) confirmed multistate outbreaks of norovirus infection and identified two new GII.4 norovirus strains (Minerva and Laurens) through partial sequencing of the major capsid (VP1) gene. Here, we report the first complete genome sequence of the GII.4 Minerva isolate. PMID- 26823590 TI - Complete Genome Sequence of KPC-Producing Klebsiella pneumoniae Strain CAV1193. AB - Carbapenem resistance in Klebsiella pneumoniae, frequently conferred by the blaKPC gene, is a major public health threat. We sequenced a blaKPC-containing strain of K. pneumoniae belonging to the emergent lineage ST941, in order to better understand the evolution of blaKPC within this species. PMID- 26823591 TI - Draft Genome Sequence of a Potential Nitrate-Dependent Fe(II)-Oxidizing Bacterium, Aquabacterium parvum B6. AB - Aquabacterium parvum B6 is a potential nitrate-dependent Fe(II)-oxidizing bacterium. The genes related to its denitrifying mechanism and iron metabolisms were unknown. We present the draft genome of Aquabacterium parvum B6, which could provide further insight into the nitrate-dependent Fe(II)-oxidizing mechanism of strain B6. PMID- 26823592 TI - Whole-Genome Sequence of Duck Tembusu Virus Strain DTMUV/CH/2014, Isolated in China. AB - The whole-complete genome sequence of a strain of duck tembusu virus (DTMUV), DTMUV/CH/2014, affecting layer ducks in China, was determined and characterized. Compared with DTMUV sequences available in GenBank, DTMUV/CH/2014 has 3 amino acid mutations located in the capsid, prM, and NS3 genes of DTMUV/CH/2014. PMID- 26823593 TI - Genome Sequence of Bovine Polyomavirus 1 Detected in a Salers Cow (Bos taurus) from Catalonia, Spain. AB - We identified a variant of the first bovine polyomavirus (BPyV1; family Polyomaviridae) in a lymph node of a Salers cow. As the 2 previously published genome sequences of this virus originated from fetal bovine serum and ground beef, respectively, this is the first BPyV1 genome that could be traced back to an individual. PMID- 26823594 TI - Genome Sequence of Highly Virulent Pseudomonas aeruginosa Strain VA-134, Isolated from a Burn Patient. AB - Infection with Pseudomonas aeruginosa leads to impairment of healing and many deaths in severe burn patients. The phenotypic diversity of P. aeruginosa strains makes it difficult to define a therapeutic strategy. Here we report the genome sequence of a highly virulent strain of P. aeruginosa, VA-134, isolated from a burn patient. PMID- 26823595 TI - Complete Genome Sequence of Corynebacterium pseudotuberculosis Strain PA01, Isolated from Sheep in Para, Brazil. AB - Corynebacterium pseudotuberculosis is the etiological agent of caseous lymphadenitis disease. In this work, we present the first complete genome sequence of Corynebacterium pseudotuberculosis strain PA01, isolated in northern Brazil from an infected sheep. The genome length is 2,337,920 bp, and 2,003 coding sequences (CDS), 12 rRNAs, and 49 tRNAs were predicted. PMID- 26823596 TI - Complete Genome Sequence of MIDG2331, a Genetically Tractable Serovar 8 Clinical Isolate of Actinobacillus pleuropneumoniae. AB - We report here the complete annotated genome sequence of a clinical serovar 8 isolate Actinobacillus pleuropneumoniae MIDG2331. Unlike the serovar 8 reference strain 405, MIDG2331 is amenable to genetic manipulation via natural transformation as well as conjugation, making it ideal for studies of gene function. PMID- 26823597 TI - Complete Genome Sequence of Corynebacterium pseudotuberculosis Viscerotropic Strain N1. AB - We present the complete genome sequence of Corynebacterium pseudotuberculosis strain N1. The sequencing was performed with the Ion Torrent Personal Genome Machine system. The genome is a circular chromosome with 2,337,845 bp, a G+C content of 52.85%, and a total of 2,045 coding sequences, 12 rRNAs, 49 tRNAs, and 58 pseudogenes. PMID- 26823598 TI - Draft Genome Sequence of Pannonibacter phragmitetus Strain CGMCC9175, a Halotolerant Polycyclic Aromatic Hydrocarbon-Degrading Bacterium. AB - Pannonibacter phragmitetus CGMCC9175 is a halotolerant polycyclic aromatic hydrocarbon (PAH)-degrading bacterium isolated from PAH-contaminated intertidal zone sediment. Here, we report the 5.7-Mb draft genome sequence of this strain, which will provide insights into the diversity of Pannonibacter and the mechanism of PAH degradation in sediments. PMID- 26823599 TI - Draft Genome Sequences of Acinetobacter baumannii Strains Harboring the blaNDM-1 Gene Isolated in Lebanon from Civilians Wounded during the Syrian Civil War. AB - We present here the draft genome sequences of multidrug-resistant blaNDM-1 positive Acinetobacter baumannii strains ACMH-6200 and ACMH-6201, isolated in north Lebanon from civilians wounded during the Syrian civil war. The draft genomes were contained in 217 contigs for ACMH-6200 and 83 contigs for ACMH-6201, including a combined 3,997,237 bases for ACMH-6200 and 3,983,110 bases for ACMH 6201, with 39% and 38.9% G+C content, respectively. PMID- 26823600 TI - Draft Genome Sequence of Bacillus amyloliquefaciens Strain RHNK22, Isolated from Rhizosphere with Biosurfactant (Surfactin, Iturin, and Fengycin) and Antifungal Activity. AB - Bacillus amyloliquefaciens strain RHNK22 isolated from groundnut rhizosphere showed direct and indirect plant growth-promoting traits along with biosurfactant activity and reduction in surface tension of water. Biosurfactants were identified as lipopeptides (surfactin, iturin, and fengycin) by molecular and biochemical analysis in our studies. PMID- 26823601 TI - Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas. AB - PURPOSE: Patients with metastatic or relapsed pediatric sarcomas receive cytotoxic regimens that induce high remission rates associated with profound lymphocyte depletion, but ultimately few survive long term. We administered adjuvant immunotherapy to patients with metastatic and recurrent pediatric sarcomas in an effort to improve outcomes. EXPERIMENTAL DESIGN: Mononuclear cells were collected via apheresis, and tumor lysate was acquired via percutaneous biopsy at enrollment. Participants received standard antineoplastic therapy, followed by autologous lymphocytes, tumor lysate/keyhole limpet hemocyanin-pulsed dendritic cell vaccinations +/- recombinant human IL7. Primary outcomes were toxicity and vaccine responses. Secondary outcomes were immune reconstitution, event-free survival, and overall survival (OS). RESULTS: Forty-three patients enrolled and 29 received immunotherapy. The regimen was well tolerated. Intent-to treat analysis demonstrated 5-year OS of 51% with significant differences based upon histologic group (63% vs. 0% for Ewing/rhabdomyosarcoma vs. other sarcomas) and response to standard therapy (74% no residual disease vs. 0% residual disease). Five-year intent-to-treat OS of patients with newly diagnosed metastatic Ewing/rhabdomyosarcoma was 77%, higher than previously reported in this population and higher than observed in a similar group treated with an earlier adjuvant immunotherapy regimen (25% 5-year OS). T-cell responses to autologous tumor lysate were identified in 62% of immunotherapy recipients, and survival was higher in those patients (73% 5-year OS with vs. 37% without immune response, P = 0.017). Immune reconstitution, measured by CD4 count recovery, was significantly enhanced in subjects treated with recombinant human IL7. CONCLUSIONS: Adjuvant immunotherapy may improve survival in patients with metastatic pediatric sarcoma. Clin Cancer Res; 22(13); 3182-91. (c)2016 AACR. PMID- 26823602 TI - Angiogenesis- and Hypoxia-Associated Proteins as Early Indicators of the Outcome in Patients with Metastatic Breast Cancer Given First-Line Bevacizumab-Based Therapy. AB - PURPOSE: We examined whether pretreatment levels of angiogenesis- or hypoxia related proteins and their changes after one cycle of first-line bevacizumab based therapy were associated with response, PFS, or OS in patients with metastatic breast cancer. EXPERIMENTAL DESIGN: We included 181 patients enrolled in the phase II ATX trial evaluating first-line paclitaxel and bevacizumab without or with capecitabine (NTR1348). Plasma samples were analyzed for VEGF-A, soluble VEGFR2 (sVEGFR2), angiopoietin 2 (ANG2), soluble TIE2 (sTIE2), IL6, IL8, and carbonic anhydrase 9 (CA9). Baseline serum CA15-3 was documented. HR was adjusted for confounding factors. Where appropriate, an optimal cut-off value defining a high and a low group was determined with Martingale residuals. RESULTS: At baseline, multiple proteins were significantly associated with PFS (ANG2, IL6, IL8, CA9, CA15-3) and OS (ANG2, sTIE2, IL6, IL8, CA9, CA15-3). After one cycle, VEGF-A, ANG2, sTIE2, and IL8 significantly decreased, while sVEGFR2 and CA9 significantly increased. The relative change in sVEGFR2 (P= 0.01) and IL8 (P= 0.001) was associated with response. Defining optimal cut-off, patients with a high CA9 rise (>2.9%) had better PFS (HR 0.45) and OS (HR 0.54) than those with low/no rise. CONCLUSIONS: Multiple angiogenesis- or hypoxia-related proteins were prognostic for PFS and OS. Molecular agents targeting these proteins might be beneficial in patients with high levels. Changes in IL8 or sVEGFR2 levels at second cycle appear predictive for response. Changes in CA9 levels during bevacizumab-based therapy for prediction of PFS and OS merit further study. PMID- 26823603 TI - Correctors of mutant CFTR enhance subcortical cAMP-PKA signaling through modulating ezrin phosphorylation and cytoskeleton organization. AB - The most common mutation of the cystic fibrosis transmembrane regulator (CFTR) gene, F508del, produces a misfolded protein resulting in its defective trafficking to the cell surface and an impaired chloride secretion. Pharmacological treatments partially rescue F508del CFTR activity either directly by interacting with the mutant protein and/or indirectly by altering the cellular protein homeostasis. Here, we show that the phosphorylation of ezrin together with its binding to phosphatidylinositol-4,5-bisphosphate (PIP2) tethers the F508del CFTR to the actin cytoskeleton, stabilizing it on the apical membrane and rescuing the sub-membrane compartmentalization of cAMP and activated PKA. Both the small molecules trimethylangelicin (TMA) and VX-809, which act as 'correctors' for F508del CFTR by rescuing F508del-CFTR-dependent chloride secretion, also restore the apical expression of phosphorylated ezrin and actin organization and increase cAMP and activated PKA submembrane compartmentalization in both primary and secondary cystic fibrosis airway cells. Latrunculin B treatment or expression of the inactive ezrin mutant T567A reverse the TMA and VX 809-induced effects highlighting the role of corrector-dependent ezrin activation and actin re-organization in creating the conditions to generate a sub-cortical cAMP pool of adequate amplitude to activate the F508del-CFTR-dependent chloride secretion. PMID- 26823604 TI - Nuclear size is sensitive to NTF2 protein levels in a manner dependent on Ran binding. AB - Altered nuclear size is associated with many cancers, and determining whether cancer-associated changes in nuclear size contribute to carcinogenesis necessitates an understanding of mechanisms of nuclear size regulation. Although nuclear import rates generally positively correlate with nuclear size, NTF2 levels negatively affect nuclear size, despite the role of NTF2 (also known as NUTF2) in nuclear recycling of the import factor Ran. We show that binding of Ran to NTF2 is required for NTF2 to inhibit nuclear expansion and import of large cargo molecules in Xenopus laevis egg and embryo extracts, consistent with our observation that NTF2 reduces the diameter of the nuclear pore complex (NPC) in a Ran-binding-dependent manner. Furthermore, we demonstrate that ectopic NTF2 expression in Xenopus embryos and mammalian tissue culture cells alters nuclear size. Finally, we show that increases in nuclear size during melanoma progression correlate with reduced NTF2 expression, and increasing NTF2 levels in melanoma cells is sufficient to reduce nuclear size. These results show a conserved capacity for NTF2 to impact on nuclear size, and we propose that NTF2 might be a new cancer biomarker. PMID- 26823605 TI - Myosin Vb mediates Cu+ export in polarized hepatocytes. AB - The cellular machinery responsible for Cu(+)-stimulated delivery of the Wilson disease-associated protein ATP7B to the apical domain of hepatocytes is poorly understood. We demonstrate that myosin Vb regulates the Cu(+)-stimulated delivery of ATP7B to the apical domain of polarized hepatic cells, and that disruption of the ATP7B-myosin Vb interaction reduces the apical surface expression of ATP7B. Overexpression of the myosin Vb tail, which competes for binding of subapical cargos to myosin Vb bound to subapical actin, disrupted the surface expression of ATP7B, leading to reduced cellular Cu(+) export. The myosin-Vb-dependent targeting step occurred in parallel with hepatocyte-like polarity. If the myosin Vb tail was expressed acutely in cells just prior to the establishment of polarity, it appeared as part of an intracellular apical compartment, centered on gamma-tubulin. ATP7B became selectively arrested in this compartment at high [Cu(+)] in the presence of myosin Vb tail, suggesting that these compartments are precursors of donor-acceptor transfer stations for apically targeted cargos of myosin Vb. Our data suggest that reduced hepatic Cu(+) clearance in idiopathic non-Wilsonian types of disease might be associated with the loss of function of myosin Vb. PMID- 26823606 TI - Translational control mediated by hnRNP K links NMHC IIA to erythroid enucleation. AB - Post-transcriptional regulation is crucial for structural and functional alterations in erythropoiesis. Enucleation of erythroid progenitors precedes reticulocyte release into circulation. In enucleated cells, reticulocyte 15 lipoxygenase (r15-LOX, also known as ALOX15) initiates mitochondria degradation. Regulation of r15-LOX mRNA translation by hnRNP K determines timely r15-LOX synthesis in terminal maturation. K562 cells induced for erythroid maturation recapitulate enucleation and mitochondria degradation. HnRNP K depletion from maturing K562 cells results in enhanced enucleation, which even occurs independently of maturation. We performed RIP-Chip analysis to identify hnRNP K interacting RNAs comprehensively. Non-muscle myosin heavy chain (NMHC) IIA (also known as MYH9) mRNA co-purified with hnRNP K from non-induced K562 cells, but not from mature cells. NMHC IIA protein increase in erythroid maturation at constant NMHC IIA mRNA levels indicates post-transcriptional regulation. We demonstrate that binding of hnRNP K KH domain 3 to a specific sequence element in the NMHC IIA mRNA 3'UTR mediates translation regulation in vitro Importantly, elevated NMHC IIA expression results in erythroid-maturation-independent enucleation as shown for hnRNP K depletion. Our data provide evidence that hnRNP-K-mediated regulation of NMHC IIA mRNA translation contributes to the control of enucleation in erythropoiesis. PMID- 26823607 TI - Role of cytonemes in Wnt transport. AB - Wnt signaling regulates a broad variety of processes during embryonic development and disease. A hallmark of the Wnt signaling pathway is the formation of concentration gradients by Wnt proteins across responsive tissues, which determines cell fate in invertebrates and vertebrates. To fulfill its paracrine function, trafficking of the Wnt morphogen from an origin cell to a recipient cell must be tightly regulated. A variety of models have been proposed to explain the extracellular transport of these lipid-modified signaling proteins in the aqueous extracellular space; however, there is still considerable debate with regard to which mechanisms allow the precise distribution of ligand in order to generate a morphogenetic gradient within growing tissue. Recent evidence suggests that Wnt proteins are distributed along signaling filopodia during vertebrate and invertebrate embryogenesis. Cytoneme-mediated transport has profound impact on our understanding of how Wnt signaling propagates through tissues and allows the formation of a precise ligand distribution in the recipient tissue during embryonic growth. In this Commentary, we review extracellular trafficking mechanisms for Wnt proteins and discuss the growing evidence of cytoneme-based Wnt distribution in development and stem cell biology. We will also discuss their implication for Wnt signaling in the formation of the Wnt morphogenetic gradient during tissue patterning. PMID- 26823608 TI - Milky Pleural Fluid. PMID- 26823609 TI - Commentary. PMID- 26823610 TI - Commentary. PMID- 26823611 TI - Effect of Blood Collection Time on Measured Delta9-Tetrahydrocannabinol Concentrations: Implications for Driving Interpretation and Drug Policy. AB - BACKGROUND: In driving-under-the-influence cases, blood typically is collected approximately 1.5-4 h after an incident, with unknown last intake time. This complicates blood Delta(9)-tetrahydrocannabinol (THC) interpretation, owing to rapidly decreasing concentrations immediately after inhalation. We evaluated how decreases in blood THC concentration before collection may affect interpretation of toxicological results. METHODS: Adult cannabis smokers (>=1*/3 months, <=3 days/week) drank placebo or low-dose alcohol (approximately 0.065% peak breath alcohol concentration) 10 min before inhaling 500 mg placebo, 2.9%, or 6.7% vaporized THC (within-individuals), then took simulated drives 0.5-1.3 h postdose. Blood THC concentrations were determined before and up to 8.3 h postdose (limit of quantification 1 MUg/L). RESULTS: In 18 participants, observed Cmax (at 0.17 h) for active (2.9 or 6.7% THC) cannabis were [median (range)] 38.2 MUg/L (11.4-137) without alcohol and 47.9 MUg/L (13.0-210) with alcohol. THC Cmax concentration decreased 73.5% (3.3%-89.5%) without alcohol and 75.1% (11.5% 85.4%) with alcohol in the first half-hour after active cannabis and 90.3% (76.1% 100%) and 91.3% (53.8%-97.0%), respectively, by 1.4 h postdose. When residual THC (from previous self-administration) was present, concentrations rapidly decreased to preinhalation baselines and fluctuated around them. During-drive THC concentrations previously associated with impairment (>=8.2 MUg/L) decreased to median <5 MUg/L by 3.3 h postdose and <2 MUg/L by 4.8 h postdose; only 1 participant had THC >=5 MUg/L after 3.3 h. CONCLUSIONS: Forensic blood THC concentrations may be lower than common per se cutoffs despite greatly exceeding them while driving. Concentrations during driving cannot be back-extrapolated because of unknown time after intake and interindividual variability in rates of decrease. PMID- 26823612 TI - What's Wrong with the Transferrin? PMID- 26823613 TI - What's Wrong with These Pleural Fluid Samples? PMID- 26823615 TI - Art Museums and Science Museums: Much More than Repositories. PMID- 26823616 TI - Bevacizumab and Temozolomide Plus Radiation Regimen for Glioblastoma Multiforme. AB - The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net. PMID- 26823617 TI - Regulation of Internet Pharmacies: A Continuing Challenge. PMID- 26823618 TI - Survey of Emergency Medicine Pharmacy Education Opportunities for Students and Residents. AB - BACKGROUND: Pharmacy services in the emergency department (ED) have been shown to decrease medication adverse events and improve patient outcomes. Anecdotally, there has been expansion of emergency medicine (EM) educational opportunities for pharmacy students and postgraduate year 1 (PGY1) pharmacy residents, however the extent of this expansion is currently unknown. OBJECTIVE: The objective of this survey study is to determine the prevalence and nature of EM pharmacy training available to pharmacy students and residents. METHODS: Electronic surveys were distributed to chairs of departments of pharmacy practice and experiential education representatives at Accreditation Council for Pharmacy Education accredited colleges or schools of pharmacy as well as residency program directors at American Society of Health-System Pharmacists-accredited postgraduate year 1 (PGY1) programs. Questions were asked related to demographics, EM introductory or advanced pharmacy practice experiences (IPPE or APPE), and PGY1 and non-EM postgraduate year 2 (PGY2) rotations. Five reminder e-mails and weekly and grand prize drawings were offered. Data that were gathered are presented utilizing descriptive statistics. RESULTS: Overall, 57/110 (52%) colleges or schools of pharmacy representatives and 286/831 (34%) residency program representatives completed the survey. Colleges or schools of pharmacy reported EM IPPEs and APPEs at 12/57 (21.1%) and 44/53 (83%), respectively. EM pharmacy rotations were available for PGY1 and non-EM PGY2 residents at 212/286 (74.1%) and 83/157 (52.9%) of institutions, respectively. CONCLUSIONS: Survey results represent the prevalence and characteristics of EM-related education opportunities for pharmacy students and residents. PMID- 26823619 TI - Evaluation of a Pharmacist-Specific Intervention on 30-Day Readmission Rates for High-Risk Patients with Pneumonia. AB - BACKGROUND: Pharmacist interventions have been shown to have an impact on reducing readmission rates, however further research is necessary to target resources to high-risk populations and determine the most effective bundle of interventions. OBJECTIVE: To evaluate the effect of a pharmacist-bundled intervention on 30-day readmission rates for high-risk patients with pneumonia. METHODS: A pilot study with a historical control conducted at a community, teaching-affiliated medical center. Up to 65 selected subjects were included if they had pneumonia and any of the following high-risk criteria: admission within 6 months, at least 5 scheduled home medications, chronic obstructive pulmonary disease (COPD), or heart failure. A retrospective chart review was conducted to compile the historical control group that received usual care between June and November 2013. Patients admitted from December 2013 through March 2014 were reviewed to receive a bundled intervention. The primary outcome was 30-day readmission rates. Risk factors and reasons for readmission, pharmacist clinical interventions, and the time interval between discharge and readmission were also evaluated. RESULTS: A trend toward a reduced 30-day readmission rate was observed in the intervention group (n = 43) compared to those who received usual care (n = 65) (27.9% vs 40.0%; relative risk [RR], 0.6977; 95% CI, 0.3965-1.2278; P = .2119). The most commonly identified high-risk inclusion criteria were having at least 5 scheduled home medications and COPD. The time interval between discharge and readmission did not considerably differ between groups (10.8 vs 10.6 days). CONCLUSIONS: The pharmacist-bundled intervention was associated with a reduced 30 day readmission rate for high-risk patients with pneumonia. PMID- 26823620 TI - Compatibility of Vancomycin and Oxacillin During Simulated Y-Site Delivery. AB - BACKGROUND: Vancomycin and oxacillin may be used together as empiric coverage in patients with proven or suspected Staphylococcus aureus infections. Though vancomycin hydrochloride 20 mg/mL and oxacillin sodium 160 mg/mL are reported to be compatible via Y-site delivery, Y-site compatibility of commonly used concentrations, vancomycin 10 mg/mL and oxacillin 20 mg/mL, has not yet been reported. OBJECTIVE: To determine the Y-site compatibility of vancomycin 10 mg/mL and oxacillin 20 mg/mL. METHODS: One vancomycin hydrochloride 1 g vial was reconstituted with 10 mL sterile water for injection (SWFI) and diluted with 90 mL 5% dextrose in water (D5W) in an evacuated intravenous (IV) bag. One oxacillin sodium 2 g vial was reconstituted with 11.5 mL sterile water for injection and diluted with 88 mL sterile water for injection in an evacuated IV bag. Three mL of each vancomycin and oxacillin were mixed in 4 test tubes to simulate Y-site delivery. Spectrometry, pH evaluation, and visual examination were performed for each test tube immediately following mixing and at 30 minutes, 1 hour, and 2 hours after mixing. RESULTS: Upon visual examination with multiple backgrounds, a white precipitant was immediately evident in the test tubes with vancomycin and oxacillin combined. Spectrometry results strongly supported evidence of precipitation throughout the duration of the experiment. CONCLUSIONS: Vancomycin 10 mg/mL and oxacillin 20 mg/mL were determined to be physically incompatible for Y-site delivery in this study, despite prior evidence that the 2 medications in different concentrations were suitable for Y-site co-administration. PMID- 26823621 TI - Secukinumab. AB - Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The September 2015 monograph topics are cangrelor, lumacaftor/ivacaftor, brexpiprazole, talimogene laherparepvec, and lesinurad. The Safety MUE is on cangrelor. PMID- 26823622 TI - Approvals, Submission, and Important Labeling Changes for US Marketed Pharmaceuticals. AB - This monthly feature will help readers keep current on new drugs, new indications, dosage forms, and safety-related changes in labeling or use. Efforts have been made to ensure the accuracy of this information; however, if there are any questions, please let me know at danial.baker@wsu.edu. PMID- 26823623 TI - Incorporating Pharmacy Scholarship to Management Responsibilities. AB - Practice advancement demands innovation. Amidst professional change, pharmacy leaders have the opportunity to collaborate with colleagues to develop transformational ideas, implement these solutions, and share those successes with professionals around the state, country, and world. Scholarship, defined as contributing to the literature through publications, presentations, and other writings, is an ideal way to advance innovation within the profession. It is critical for pharmacy leaders to build scholarship into their professional workflow. Ensuring that successful projects are published or presented may translate into shared best practices. Many pharmacy leaders may find it difficult to participate in scholarship activities because of their busy schedules. This column serves to outline recommendations on how to effectively incorporate writing for publications, making presentations, and other scholarly work into the role of pharmacy leaders and managers. To reduce the barriers to scholarship, pharmacy leaders role can apply project management principles to their work and identify projects that otherwise would not be published and support their development. PMID- 26823624 TI - Use of Highly Fortified Products among US Adults. AB - It is complicated to ascertain the composition and prevalence of the use of highly fortified food and supplement products (HFPs) because HFP foods and HFP supplements have different labeling requirements. However, HFPs (energy bars, energy drinks, sports drinks, protein bars, energy shots, and fortified foods/beverages) are popular in the United States. A web-based survey balanced to reflect US census data was used to describe their use in a sample of 2,355 US adults >18 yr in 2011 and trends in their use from 2005. In 2011, 33% of adults reported using HFP; use was significantly higher among males, African Americans, Hispanics, and more highly educated individuals (e.g. some college or more) and those <45 yr compared to non-users. Multiple product use was common. Of users, 46% consumed sports drinks, 37% fortified foods/beverages, 32% protein bars, 27% energy drinks, 24% energy bars, and 12% energy shots. For those HFP products as a group, prevalence of use was 36% (n=2039) in 2005, 35% in 2009 (n=2010), and 30% in 2011 (n=2355). Although use was significantly lower in 2011 than in 2005 especially among females, non-Hispanics, and those with high school education or less (P<=0.05). HFP, particularly energy and sports drinks, continue to be widely used by many U.S. adults. PMID- 26823626 TI - Molecular systematics of Barbatosphaeria (Sordariomycetes): multigene phylogeny and secondary ITS structure. AB - Thirteen morphologically similar strains of barbatosphaeria- and tectonidula-like fungi were studied based on the comparison of cultural and morphological features of sexual and asexual morphs and phylogenetic analyses of five nuclear loci, i.e. internal transcribed spacer rDNA operon (ITS), large and small subunit nuclear ribosomal DNA, beta-tubulin, and second largest subunit of RNA polymerase II. Phylogenetic results were supported by in-depth comparative analyses of common core secondary structure of ITS1 and ITS2 in all strains and the identification of non-conserved, co-evolving nucleotides that maintain base pairing in the RNA transcript. Barbatosphaeria is defined as a well-supported monophyletic clade comprising several lineages and is placed in the Sordariomycetes incertae sedis. The genus is expanded to encompass nine species with both septate and non-septate ascospores in clavate, stipitate asci with a non-amyloid apical annulus and non stromatic ascomata with a long decumbent neck and carbonised wall often covered by pubescence. The asexual morphs are dematiaceous hyphomycetes with holoblastic conidiogenesis belonging to Ramichloridium and Sporothrix types. The morphologically similar Tectonidula, represented by the type species T. hippocrepida, grouped with members of Barbatosphaeria and is transferred to that genus. Four new species are introduced and three new combinations in Barbatosphaeria are proposed. A dichotomous key to species accepted in the genus is provided. PMID- 26823627 TI - Green and brown bridges between weeds and crops reveal novel Diaporthe species in Australia. AB - Diaporthe (syn. Phomopsis) species are well-known saprobes, endophytes or pathogens on a range of plants. Several species have wide host ranges and multiple species may sometimes colonise the same host species. This study describes eight novel Diaporthe species isolated from live and/or dead tissue from the broad acre crops lupin, maize, mungbean, soybean and sunflower, and associated weed species in Queensland and New South Wales, as well as the environmental weed bitou bush (Chrysanthemoides monilifera subsp. rotundata) in eastern Australia. The new taxa are differentiated on the basis of morphology and DNA sequence analyses based on the nuclear ribosomal internal transcribed spacer region, and part of the translation elongation factor-1alpha and beta-tubulin genes. The possible agricultural significance of live weeds and crop residues ('green bridges') as well as dead weeds and crop residues ('brown bridges') in aiding survival of the newly described Diaporthe species is discussed. PMID- 26823625 TI - Phylogeography and evolutionary patterns in Sporothrix spanning more than 14 000 human and animal case reports. AB - Pathology to vertebrate hosts has emerged repeatedly in the order Ophiostomatales. Occasional infections have been observed in Sporothrix mexicana at a low level of virulence, while the main pathogenic species cluster in a derived clade around S. schenckii s.str. In this paper, phylogeny and epidemiology of the members of this clade were investigated for 99 clinical and 36 environmental strains using four genetic loci, viz. rDNA ITS and partial CAL, TEF1, and TEF3; data are compared with amplified fragment length polymorphism (AFLP) genotyping. The four main species of the pathogenic clade were recognised. The species proved to show high degrees of endemicity, which enabled interpretation of literature data where live material or genetic information is lacking. The clade of four species comprised nine subclusters, which often had limited geographic distribution and were separate from each other in all partitions, suggesting low degrees of interbreeding between populations. In contrast, S. globosa exhibited consistent global distribution of identical AFLP types, suggesting another type of dispersal. Sporothrix brasiliensis is known to be involved in an expanding zoonosis and transmitted by cats, whereas S. globosa infections originated from putrid plant material, causing a sapronosis. Sporothrix schenckii s.str., the most variable species within the clade, also had a plant origin, with ecological similarities to that of S. globosa. A hypothesis was put forward that highly specific conditions in the plant material are required to promote the growth of Sporothrix. Fermented, self-heated plant debris may stimulate the thermodependent yeast-like invasive form of the fungus, which facilitates repeated infection of mammals. PMID- 26823628 TI - A co-evolutionary relationship exists between Endoraecium (Pucciniales) and its Acacia hosts in Australia. AB - Endoraecium is a genus of rust fungi that infects several species of Acacia in Australia, South-East Asia and Hawaii. This study investigated the systematics of Endoraecium from 55 specimens in Australia based on a combined morphological and molecular approach. Phylogenetic analyses were conducted on partitioned datasets of loci from ribosomal and mitochondrial DNA. The recovered molecular phylogeny supported a recently published taxonomy based on morphology and host range that divided Endoraecium digitatum into five species. Spore morphology is synapomorphic and there is evidence Endoraecium co-evolved with its Acacia hosts. The broad host ranges of E. digitatum, E. parvum, E. phyllodiorum and E. violae faustiae are revised in light of this study, and nine new species of Endoraecium are described from Australia based on host taxonomy, morphology and phylogenetic concordance. PMID- 26823629 TI - Unravelling Colletotrichum species associated with Camellia: employing ApMat and GS loci to resolve species in the C. gloeosporioides complex. AB - We investigated the phylogenetic diversity of 144 Colletotrichum isolates associated with symptomatic and asymptomatic tissues of Camellia sinensis and other Camellia spp. from seven provinces in China (Fujian, Guizhou, Henan, Jiangxi, Sichuan, Yunnan, Zhejiang), and seven isolates obtained from other countries, including Indonesia, UK, and the USA. Based on multi-locus (ACT, ApMat, CAL, GAPDH, GS, ITS, TUB2) phylogenetic analyses and phenotypic characters, 11 species were distinguished, including nine well-characterised species (C. alienum, C. boninense, C. camelliae, C. cliviae, C. fioriniae, C. fructicola, C. gloeosporioides, C. karstii, C. sia-mense), and two novel species (C. henanense and C. jiangxiense). Of these, C. camelliae proved to be the most dominant and probably host specific taxon occurring on Camellia. An epitype is also designated for the latter species in this study. Colletotrichum jiangxiense is shown to be phylogenetically closely related to the coffee berry pathogen C. kahawae subsp. kahawae. Pathogenicity tests and the pairwise homoplasy index test suggest that C. jiangxiense and C. kahawae subsp. kahawae are two independent species. This study represents the first report of C. alienum and C. cliviae occurring on Camellia sinensis. In addition, our study demonstrated that the combined use of the loci ApMat and GS in a phylogenetic analysis is able to resolve all currently accepted species in the C. gloeosporioides species complex. PMID- 26823630 TI - Dark septate endophytic pleosporalean genera from semiarid areas. AB - Dark septate endophytes (DSE) are distributed worldwide as root-colonising fungi, and frequent in environments with strong abiotic stress. DSE is not a taxon, but constitutes numerous fungal taxa belonging to several orders of Ascomycota. In this study we investigate three unidentified DSE lineages belonging to Pleosporales that were found previously in semiarid sandy grasslands. For molecular phylogenetic studies seven loci (ITS, partial 18S nrRNA, 28S nrRNA, actin, calmodulin, transcription-elongation factor 1- alpha and beta -tubulin genes) were amplified and sequenced. Based on morphology and the resulting molecular phylogeny these isolates were found to represent three novel genera within the Pleosporales, namely Aquilomyces, Flavomyces and Darksidea, with eight novel species. Molecular data revealed that monotypic Aquilomyces belongs to Morosphaeriaceae, monotypic Flavomyces represents an incertae sedis lineage related to Massarinaceae, and Darksidea, with six new species, is allied to the Lentitheciaceae. During this study we tested numerous conditions to induce sporulation, and managed for the first time to induce several DSE to form their sexual morphs. PMID- 26823631 TI - Decrypting the Hebeloma crustuliniforme complex: European species of Hebeloma section Denudata subsection Denudata (Agaricales). AB - Hebeloma subsection Denudata includes the type of H. section Denudata, Hebeloma crustuliniforme, as well as the majority of the taxa commonly included in the Hebeloma crustuliniforme complex. Complementing the work of D.K. Aanen and co workers, and using refined morphological and molecular methods we were able to recognize further individual taxa within the section. Fifteen species occurring in Europe are assigned to H. subsect. Denudata. Of these, we describe eight species as new, namely H. aanenii, H. aurantioumbrinum, H. geminatum, H. louiseae, H. luteicystidiatum, H. pallidolabiatum, H. perexiguum and H. salicicola. Naucoria bellotiana, a species very similar to H. alpinum is recombined into Hebeloma. A key to Hebeloma subsect. Denudata is provided. We demonstrate that within this subsection there is good overall consistency between morphological, phylogenetic and biological species concepts. In contrast to current opinion, in this group there is little species overlap, particularly when also considering species frequencies, between arctic and alpine floras on one hand and temperate on the other. PMID- 26823632 TI - Species limits and relationships within Otidea inferred from multiple gene phylogenies. AB - The genus Otidea is one of the more conspicuous members of the Pyronemataceae, with high species diversity in hemiboreal and boreal forests. The genus is morphologically coherent and in previous higher-level multi-gene analyses it formed a highly supported monophyletic group. Species delimitation within Otidea is controversial and much confusion has prevailed in the naming of taxa. To provide a phylogenetic hypothesis of Otidea, elucidate species diversity and limits we compiled a four-gene dataset including the nuclear LSU rDNA and three nuclear protein-coding genes (RPB1, RPB2 and EF-1alpha) for 89 specimens (total 4 877 nucleotides). These were selected from a larger sample of material studied using morphology and 146 ITS (ITS1-5.8S-ITS2) and 168 LSU rDNA sequences to represent the full genetic diversity. Using genealogical concordance phylogenetic species recognition (GCPSR), Bayesian and maximum likelihood analyses of the individual datasets resolved 25 species of Otidea. An additional eight singletons are considered to be distinct species, because they were genetically divergent from their sisters. Sequences of multiple genes were included from 13 holotypes, one neotype and three epitypes. Otidea angusta, O. myosotis and O. papillata f. pallidefurfuracea are nested within O. nannfeldtii, O. leporina and O. tuomikoskii, respectively and are considered synonyms. Otidea cantharella var. minor is shown to be a distinct species. Five new species were discovered: O. oregonensis and O. pseudoleporina for North America; and O. borealis, O. brunneoparva and O. subformicarum for Europe. The analyses of the individual four gene datasets yielded phylogenies that were highly concordant topologically, except for the RPB1 that showed supported conflict for some nodes in Bayesian analysis. Excluding the RPB1 from the combined analyses produced an identical topology to the four-gene phylogeny, but with higher support for several basal nodes and lower support for several shallow nodes. We argue to use the three-gene dataset to retrieve the maximum support for the higher-level relationships in Otidea, but still utilise the signal from the RPB1 for the delimitation and relationships of closely related species. From the four gene regions utilised, EF 1alpha and RPB1 have the strongest species recognition power, and with higher amplification success EF-1alpha may serve as the best secondary barcoding locus for Otidea (with ITS being a primary). The phylogeny from the three- and four gene datasets is fully resolved and strongly supported in all branches but one. Two major clades, as part of six inclusive clades A-F, are identified - and ten subclades within these: A) O. platyspora and O. alutacea subclades, and B) O. papillata, O. leporina, O. tuomikoskii, O. cantharella, O. formicarum, O. unicisa, O. bufonia-onotica and O. concinna subclades. Morphological features in Otidea appear to be fast evolving and prone to shifts, and are poor indicators of higher-level relationships. Nevertheless, a conspicuous spore ornament is a synapomorphy for the O. unicisa subclade (/Otideopsis); all other species in Otidea have smooth or verruculose (in SEM) spores. Exclusively pale to bright yellow apothecia and straight to curved, broadly clavate to distinctly capitate paraphyses are synapomorphies for a restricted O. concinna subclade (/Flavoscypha). The curved to hooked apices of the paraphyses is suggested to be a symplesiomorphic trait for the genus. The reaction of resinous exudates on the outermost excipular cells that coalesce into amber drops in Melzer's reagent is likely an ancestral state for clade B. We estimate that Otidea consists of 47 species worldwide, based on all available information (including morphology, ITS or LSU sequences, and literature descriptions). Three fifths of the species occur in Europe, with 20 species recognised as endemic. At least 14 species occur in North America and 17 in Asia, with eight and ten species considered endemic to each continent, respectively. Our knowledge about Otidea in Asia is still fragmentary and the diversity likely much higher. PMID- 26823633 TI - A monograph of Otidea (Pyronemataceae, Pezizomycetes). AB - The easily recognised genus Otidea is subjected to numerous problems in species identification. A number of old names have undergone various interpretations, materials from different continents have not been compared and misidentifications occur commonly. In this context, Otidea is monographed, based on our multiple gene phylogenies assessing species boundaries and comparative morphological characters (see Hansen & Olariaga 2015). All names combined in or synonymised with Otidea are dealt with. Thirty-three species are treated, with full descriptions and colour illustrations provided for 25 of these. Five new species are described, viz. O. borealis, O. brunneoparva, O. oregonensis, O. pseudoleporina and O. subformicarum. Otidea cantharella var. minor and O. onotica var. brevispora are elevated to species rank. Otideopsis kaushalii is combined in the genus Otidea. A key to the species of Otidea is given. An LSU dataset containing 167 sequences (with 44 newly generated in this study) is analysed to place collections and determine whether the named Otidea sequences in GenBank were identified correctly. Fourty-nine new ITS sequences were generated in this study. The ITS region is too variable to align across Otidea, but had low intraspecific variation and it aided in species identifications. Thirty type collections were studied, and ITS and LSU sequences are provided for 12 of these. A neotype is designated for O. cantharella and epitypes for O. concinna, O. leporina and O. onotica, along with several lectotypifications. The apothecial colour and shape, and spore characters are important for species identification. We conclude that to distinguish closely related or morphologically similar species, a combination of additional features are needed, i.e. the shape of the paraphyses, ectal excipulum structure, types of ectal excipulum resinous exudates and their reactions in Melzer's reagent and KOH, tomentum and basal mycelium colours and exudates. The KOH reaction of excipular resinous exudates and basal mycelium are introduced as novel taxonomic characters. PMID- 26823634 TI - Towards a phylogenetic reappraisal of Parmulariaceae and Asterinaceae (Dothideomycetes). AB - Members of the Asterinaceae and Parmulariaceae are obligate biotrophic fungi with a pantropical distribution that grow in direct association with living plant tissues and produce external ascomata and bitunicate asci. These fungi are poorly known, with limited information about their taxonomic position in the Dothideomycetes. Much of what is known is conjectural and based on observation of morphological characters. An assessment of the phylogenetic position of the Asterinaceae and Parmulariaceae is provided based on a phylogenetic analysis of the nrDNA operon (ITS) and the large subunit rDNA (LSU) sequence data obtained from fresh material of selected species collected in Brazil. Three key species were included and epitypified, namely Asterina melastomatis, which is the type species for the type genus of the Asterinaceae; Prillieuxina baccharidincola (Asterinaceae); and Parmularia styracis, which is the type species for the type genus of the Parmulariaceae. An LSU rDNA phylogenetic analysis was performed indicating the correct phylogenetic placement of the Asterinales within the Dothideomycetes. From this initial analysis it is clear that the Parmulariaceae as currently circumscribed is polyphyletic, and that the Asterinaceae and Parmulariaceae are related, which justifies the maintenance of the order Asterinales. Asterotexis cucurbitacearum is recognised as distinct from other Dothideomycetes and placed in the newly proposed family and order (Asterotexiaceae, Asterotexiales), while the higher order phylogeny of Inocyclus angularis remains unresolved. Additionally, Lembosia abaxialis is introduced as a novel species and the phylogenetic placement of the genera Batistinula and Prillieuxina is clarified. PMID- 26823638 TI - A Model-Free Scheme for Meme Ranking in Social Media. AB - The prevalence of social media has greatly catalyzed the dissemination and proliferation of online memes (e.g., ideas, topics, melodies, tags, etc.). However, this information abundance is exceeding the capability of online users to consume it. Ranking memes based on their popularities could promote online advertisement and content distribution. Despite such importance, few existing work can solve this problem well. They are either daunted by unpractical assumptions or incapability of characterizing dynamic information. As such, in this paper, we elaborate a model-free scheme to rank online memes in the context of social media. This scheme is capable to characterize the nonlinear interactions of online users, which mark the process of meme diffusion. Empirical studies on two large-scale, real-world datasets (one in English and one in Chinese) demonstrate the effectiveness and robustness of the proposed scheme. In addition, due to its fine-grained modeling of user dynamics, this ranking scheme can also be utilized to explain meme popularity through the lens of social influence. PMID- 26823637 TI - Adaptation of a methanogenic consortium to arsenite inhibition. AB - Arsenic (As) is a ubiquitous metalloid known for its adverse effects to human health. Microorganisms are also impacted by As toxicity, including methanogenic archaea, which can affect the performance of process in which biological activity is required (i.e. stabilization of activated sludge in wastewater treatment plants). The novel ability of a mixed methanogenic granular sludge consortium to adapt to the inhibitory effect of arsenic (As) was investigated by exposing the culture to approximately 0.92 mM of AsIII for 160 d in an arsenate (AsV) reducing bioreactor using ethanol as the electron donor. The results of shaken batch bioassays indicated that the original, unexposed sludge was severely inhibited by arsenite (AsIII) as evidenced by the low 50% inhibition concentrations (IC50) determined, i.e., 19 and 90 MUM for acetoclastic- and hydrogenotrophic methanogenesis, respectively. The tolerance of the acetoclastic and hydrogenotrophic methanogens in the sludge to AsIII increased 47-fold (IC50 = 910 MUM) and 12-fold (IC50= 1100 MUM), respectively, upon long-term exposure to As. In conclusion, the methanogenic community in the granular sludge demonstrated a considerable ability to adapt to the severe inhibitory effects of As after a prolonged exposure period. PMID- 26823636 TI - Fungal Planet description sheets: 371-399. AB - Novel species of fungi described in the present study include the following from Australia: Neoseptorioides eucalypti gen. & sp. nov. from Eucalyptus radiata leaves, Phytophthora gondwanensis from soil, Diaporthe tulliensis from rotted stem ends of Theobroma cacao fruit, Diaporthe vawdreyi from fruit rot of Psidium guajava, Magnaporthiopsis agrostidis from rotted roots of Agrostis stolonifera and Semifissispora natalis from Eucalyptus leaf litter. Furthermore, Neopestalotiopsis egyptiaca is described from Mangifera indica leaves (Egypt), Roussoella mexicana from Coffea arabica leaves (Mexico), Calonectria monticola from soil (Thailand), Hygrocybe jackmanii from littoral sand dunes (Canada), Lindgomyces madisonensis from submerged decorticated wood (USA), Neofabraea brasiliensis from Malus domestica (Brazil), Geastrum diosiae from litter (Argentina), Ganoderma wiiroense on angiosperms (Ghana), Arthrinium gutiae from the gut of a grasshopper (India), Pyrenochaeta telephoni from the screen of a mobile phone (India) and Xenoleptographium phialoconidium gen. & sp. nov. on exposed xylem tissues of Gmelina arborea (Indonesia). Several novelties are introduced from Spain, namely Psathyrella complutensis on loamy soil, Chlorophyllum lusitanicum on nitrified grasslands (incl. Chlorophyllum arizonicum comb. nov.), Aspergillus citocrescens from cave sediment and Lotinia verna gen. & sp. nov. from muddy soil. Novel foliicolous taxa from South Africa include Phyllosticta carissicola from Carissa macrocarpa, Pseudopyricularia hagahagae from Cyperaceae and Zeloasperisporium searsiae from Searsia chirindensis. Furthermore, Neophaeococcomyces is introduced as a novel genus, with two new combinations, N. aloes and N. catenatus. Several foliicolous novelties are recorded from La Reunion, France, namely Ochroconis pandanicola from Pandanus utilis, Neosulcatispora agaves gen. & sp. nov. from Agave vera-cruz, Pilidium eucalyptorum from Eucalyptus robusta, Strelitziana syzygii from Syzygium jambos (incl. Strelitzianaceae fam. nov.) and Pseudobeltrania ocoteae from Ocotea obtusata (Beltraniaceae emend.). Morphological and culture characteristics along with ITS DNA barcodes are provided for all taxa. PMID- 26823635 TI - One fungus, which genes? Development and assessment of universal primers for potential secondary fungal DNA barcodes. AB - The aim of this study was to assess potential candidate gene regions and corresponding universal primer pairs as secondary DNA barcodes for the fungal kingdom, additional to ITS rDNA as primary barcode. Amplification efficiencies of 14 (partially) universal primer pairs targeting eight genetic markers were tested across > 1 500 species (1 931 strains or specimens) and the outcomes of almost twenty thousand (19 577) polymerase chain reactions were evaluated. We tested several well-known primer pairs that amplify: i) sections of the nuclear ribosomal RNA gene large subunit (D1-D2 domains of 26/28S); ii) the complete internal transcribed spacer region (ITS1/2); iii) partial beta -tubulin II (TUB2); iv) gamma-actin (ACT); v) translation elongation factor 1-alpha (TEF1alpha); and vi) the second largest subunit of RNA-polymerase II (partial RPB2, section 5-6). Their PCR efficiencies were compared with novel candidate primers corresponding to: i) the fungal-specific translation elongation factor 3 (TEF3); ii) a small ribosomal protein necessary for t-RNA docking; iii) the 60S L10 (L1) RP; iv) DNA topoisomerase I (TOPI); v) phosphoglycerate kinase (PGK); vi) hypothetical protein LNS2; and vii) alternative sections of TEF1alpha. Results showed that several gene sections are accessible to universal primers (or primers universal for phyla) yielding a single PCR-product. Barcode gap and multi dimensional scaling analyses revealed that some of the tested candidate markers have universal properties providing adequate infra- and inter-specific variation that make them attractive barcodes for species identification. Among these gene sections, a novel high fidelity primer pair for TEF1alpha, already widely used as a phylogenetic marker in mycology, has potential as a supplementary DNA barcode with superior resolution to ITS. Both TOPI and PGK show promise for the Ascomycota, while TOPI and LNS2 are attractive for the Pucciniomycotina, for which universal primers for ribosomal subunits often fail. PMID- 26823640 TI - One Year of Preschool or Two - Is It Important for Adult Outcomes? Results from the Chicago Longitudinal Study of the Child-Parent Centers. AB - Until the last year, public funding for preschool education had been growing rapidly over a decade with most state programs providing one year of preschool for four year olds. Fewer three year olds are enrolled in preschool. To investigate the importance of enrollment duration, this study is the first to estimate long-term dosage effects of years of preschool. We use data from a cohort of 1,500 students in the Chicago Longitudinal Study who enrolled in the Chicago Public Schools in the mid-1980s. Many of these students participated in a high-quality preschool program called Child-Parent Centers (CPC) for one or two years. To address selection with multiple treatments, we employ inverse propensity score weighting. Relative to children who attended one year of CPC preschool, the two-year group is significantly less likely to receive special education or be abused or neglected or to commit crimes. The findings provide support for the long-term benefits of greater exposure to preschool. PMID- 26823639 TI - A Qualitative Study on the Types and Purposes of Social Activities in Late Life. AB - This qualitative study examines older adults' subjective views on the types and purposes of social activities. In-depth interviews were conducted with a purposive sample of 20 older adults, with low (n = 10) and high (n = 10) memory performance. We used grounded theory methods to analyze the narrative data. Four types of social activities-Altruism, Creativity, Game, and Motion-were identified. The purpose of social activities included enjoyment, relaxation, stimulation, and belongingness. Those in the low memory group seemed to face more barriers to participation. Different types of social activities may be important for cognitive health and well-being. PMID- 26823642 TI - Exploring the state of health and safety management system performance measurement in mining organizations. AB - Complex arguments continue to be articulated regarding the theoretical foundation of health and safety management system (HSMS) performance measurement. The culmination of these efforts has begun to enhance a collective understanding. Despite this enhanced theoretical understanding, however, there are still continuing debates and little consensus. The goal of the current research effort was to empirically explore common methods to HSMS performance measurement in mining organizations. The purpose was to determine if value and insight could be added into the ongoing approaches of the best ways to engage in health and safety performance measurement. Nine site-level health and safety management professionals were provided with 133 practices corresponding to 20 HSMS elements, each fitting into the plan, do, check, act phases common to most HSMS. Participants were asked to supply detailed information as to how they (1) assess the performance of each practice in their organization, or (2) would assess each practice if it were an identified strategic imperative. Qualitative content analysis indicated that the approximately 1200 responses provided could be described and categorized into interventions, organizational performance, and worker performance. A discussion of how these categories relate to existing indicator frameworks is provided. The analysis also revealed divergence in two important measurement issues; (1) quantitative vs qualitative measurement and reporting; and (2) the primary use of objective or subjective metrics. In lieu of these findings we ultimately recommend a balanced measurement and reporting approach within the three metric categories and conclude with suggestions for future research. PMID- 26823641 TI - Immunoexpression of Ki-67, MCM2, and MCM3 in Ameloblastoma and Ameloblastic Carcinoma and Their Correlations with Clinical and Histopathological Patterns. AB - Cell proliferation assays are performed using antibodies against nuclear proteins associated with DNA replication. These nuclear proteins have gained special interest to predict the biological and clinical behaviors of various tumors. The aim of this study was to analyze the presence of Ki-67 protein and the minichromosome maintenance-2 (MCM2) and maintenance-3 (MCM3) proteins in ameloblastoma. Materials and Methods. Cell proliferation marker expression levels were assessed via immunohistochemistry in 111 ameloblastoma cases (72 unicystic ameloblastoma samples, 38 solid/multicystic ameloblastoma samples, and 1 ameloblastic carcinoma). The label index was performed as described previously. Results. MCM2 and MCM3 showed higher proliferation indexes in all variants of ameloblastoma compared to the classic marker Ki-67. No correlation between the proliferation index and the clinical and protein expression data was observed. Conclusion. The results suggest that clinical features do not directly affect tumor cell proliferation. Moreover, the high levels of cellular proliferation of MCM2 and MCM3 compared with Ki-67 may indicate that MCM2 and MCM3 are more sensitive markers for predicting the growth rate and eventually might be helpful as a tool for predicting aggressive and recurrent behaviors in these tumors. PMID- 26823643 TI - A Useful Modification of the Evans Magnesium Halide-Catalyzed anti-Aldol Reaction: Application to Enolizable Aldehydes. AB - A practical protocol for use of the magnesium halide-catalyzed anti-aldol reaction of an Evans N-acyloxazolidinone with enolizable aldehydes is reported. The yields of anti-aldol adducts for saturated or unsaturated and branched or unbranched aliphatic aldehydes are preparatively useful. PMID- 26823644 TI - Overview of Polycyclic Aromatic Compounds (PAC). AB - The chemical group of polycyclic aromatic compounds (PAC), including the better known subgroup of polycyclic aromatic hydrocarbons (PAH) and the heterocyclic aromatic compounds (NSO-PAC, heterocycles), comprise several thousand individual compounds. It is hard to find a comprehensive overview in the literature of these PACs that includes a substantial amount of relevant properties. Here an attempt is made to summarize the most studied but also some less well-known PACs. In addition to basic data such as recommended names, abbreviations, CAS numbers, molecular formulas, chemical structures, and exact mono-isotopic molecular weights, physico-chemical properties taken from the literature like boiling points, vapor pressures, water solubilities, Henry's Law constants, n-octanol water partition coefficients (log KOW), and pKa are summarized. Selected toxicological data are listed indicating carcinogenic and mutagenic activity or effects on different organisms. PAC nomenclature is a complex topic, so suggestions for practical use are made. Regarding available data, estimated (instead of measured) values should be used with caution because considerable deviations from experimentally determined values can occur. For an enhanced understanding of the behavior of single PACs in comparison with each other, some of the properties mentioned above are plotted vs. the number of rings or the degree of alkylation. Also, some physico-chemical data are correlated with different functional groups as substituents of the PAHs. This article reveals that rather little is known about the less common PACs, e.g., higher molecular weight compounds, alkylated or otherwise substituted aromatics, for instance, keto-, oxo-, amino-, nitro-, cyano-PAHs, or some heterocyclic aromatic compounds, including their derivatives. It mirrors the limited state of knowledge about the variety of PACs that do not belong to the 16 EPA PAHs. PMID- 26823645 TI - Time to Say Goodbye to the 16 EPA PAHs? Toward an Up-to-Date Use of PACs for Environmental Purposes. AB - The 16 EPA PAHs have played an exceptionally large role above all in environmental and analytical sciences in the last 40 years, but now there are good reasons to question their utility in many circumstances even though their use is so established and comfortable. Here we review the reasons why the list has been so successful and why sometimes it is seen as less relevant. Three groups of polycyclic aromatic compounds (PAC) are missing: larger and highly relevant PAHs, alkylated PACs, and compounds containing heteroatoms. Attempts to improve the situation for certain matrixes are known and here: (1) an updated list of PAHs (including the 16 EPA PAHs) for the evaluation of the toxicity in the environment (40 EnvPAHs); (2) a list of 23 NSO-heterocyclic compounds and 6 heterocyclic metabolites; and (3) lists of 10 oxy-PAHs and 10 nitro-PAHs are proposed for practical use in the future. A discussion in the scientific community about these lists is invited. Although the state of knowledge has improved dramatically since the introduction of the 16 EPA PAHs in the 1970s, this summary also shows that more research is needed about the toxicity, occurrence in the environment and chemical analysis, particularly of alkylated PAHs, higher molecular weight PAHs and substituted PACs such as amino-PAHs, cyano PAHs, etc.. We also suggest that a long overdue discussion of an update of regulatory environmental PAH analysis is initiated. PMID- 26823646 TI - Premature Atherosclerotic Cardiovascular Disease in Childhood Cancer Survivors. AB - Survival rates of childhood cancer have increased over the last 30 years, revealing a population with unique characteristics and risks. The effects of radiation and cardiotoxic chemotherapy predispose these children to both early and late cardiovascular disease. Cranial radiation also increases the likelihood of growth hormone deficiency, which leads to metabolic disturbances. Childhood cancer survivors are less likely to be active than their healthy siblings, and have a lower aptitude for physical activity. These issues are additive to the usual risks experienced by the general population, thereby significantly increasing the likelihood of premature cardiovascular disease. Early and regular screening and risk factor management in this population is recommended. PMID- 26823647 TI - Maternal Tenofovir Disoproxil Fumarate Use in Pregnancy and Growth Outcomes among HIV-Exposed Uninfected Infants in Kenya. AB - BACKGROUND: Tenofovir disoproxil fumarate (TDF) is commonly used in antiretroviral treatment (ART) and preexposure prophylaxis regimens. We evaluated the relationship of prenatal TDF use and growth outcomes among Kenyan HIV-exposed uninfected (HEU) infants. MATERIALS AND METHODS: We included PCR-confirmed HEU infants enrolled in a cross-sectional survey of mother-infant pairs conducted between July and December 2013 in Kenya. Maternal ART regimen during pregnancy was determined by self-report and clinic records. Six-week and 9-month z-scores for weight-for-age (WAZ), weight-for-length (WLZ), length-for-age (LAZ), and head circumference-for-age (HCAZ) were compared among HEU infants with and without TDF exposure using t-tests and multivariate linear regression models. RESULTS: Among 277 mothers who received ART during pregnancy, 63% initiated ART before pregnancy, of which 89 (32%) used TDF. No differences in birth weight (3.0 kg versus 3.1 kg, p = 0.21) or gestational age (38 weeks versus 38 weeks, p = 0.16) were detected between TDF-exposed and TDF-unexposed infants. At 6 weeks, unadjusted mean WAZ was lower among TDF-exposed infants (-0.8 versus -0.4, p = 0.03), with a trend towards association in adjusted analyses (p = 0.06). There were no associations between prenatal TDF use and WLZ, LAZ, and HCAZ in 6-week or 9-month infant cohorts. CONCLUSION: Maternal TDF use did not adversely affect infant growth compared to other regimens. PMID- 26823649 TI - Epigenetic Regulation of Tissue-Type Plasminogen Activator in Human Brain Tissue and Brain-Derived Cells. AB - The serine protease tissue-type plasminogen activator (t-PA) is involved in both vital physiological brain processes, such as synaptic plasticity, and pathophysiological conditions, such as neurodegeneration and ischemic stroke. Recent data suggest that epigenetic mechanisms play an important role in the regulation of t-PA in human endothelial cells. However, there are limited data on epigenetic regulation of t-PA in human brain-derived cells. We demonstrate that treatment of cultured human neurons and human astrocytes with the histone deacetylase inhibitors trichostatin A (TSA) and MS-275 resulted in a two- to threefold increase in t-PA mRNA and protein expression levels. Next, we performed a chromatin immunoprecipitation assay on treated astrocytes with antibodies directed against acetylated histones H3 and H4 (both markers of gene activation). Treatment with MS-275 and TSA for 24 hours resulted in a significant increase in H3 acetylation, which could explain the observed increase in t-PA gene activity after the inhibition of histone deacety-lation. Furthermore, DNA methylation analysis of cultured human neurons and astrocytes, as well as human postmortem brain tissue, revealed a stretch of unmethylated CpG dinucleotides in the proximal t-PA promoter, whereas more upstream CpGs were highly methylated. Taken together, these results implicate involvement of epigenetic mechanisms in the regulation of t-PA expression in the human brain. PMID- 26823648 TI - Genome Sequence and Analysis of Peptoclostridium difficile Strain ZJCDC-S82. AB - Peptoclostridium difficile (Clostridium difficile) is the major pathogen associated with infectious diarrhea in humans. Concomitant with the increased incidence of C. difficile infection worldwide, there is an increasing concern regarding this infection type. This study reports a draft assembly and detailed sequence analysis of C. difficile strain ZJCDC-S82. The de novo assembled genome was 4.19 Mb in size, which includes 4,013 protein-coding genes, 41 rRNA genes, and 84 tRNA genes. Along with the nuclear genome, we also assembled sequencing information for a single plasmid consisting of 11,930 nucleotides. Comparative genomic analysis of C. difficile ZJCDC-S82 and two other previously published strains, such as M120 and CD630, showed extensive similarity. Phylogenetic analysis revealed that genetic diversity among C. difficile strains was not influenced by geographic location. Evolutionary analysis suggested that four genes encoding surface proteins exhibited positive selection in C. difficile ZJCDC-S82. Codon usage analysis indicated that C. difficile ZJCDC-S82 had high codon usage bias toward A/U-ended codons. Furthermore, codon usage patterns in C. difficile ZJCDC-S82 were predominantly affected by mutation pressure. Our results provide detailed information pertaining to the C. difficile genome associated with a strain from mainland China. This analysis will facilitate the understanding of genomic diversity and evolution of C. difficile strains in this region. PMID- 26823650 TI - Expression and Presence of OPG and RANKL mRNA and Protein in Human Periodontal Ligament with Orthodontic Force. AB - OBJECTIVE: The objective of this study is to investigate the expression and concentration of ligand receptor activator of NFkB (RANKL) and osteoprotegerin (OPG) in human periodontal ligament (hPDL) with orthodontic forces of different magnitudes. METHODS: Right premolars in 32 patients were loaded with 4oz or 7oz of orthodontic force for 7 days. Left first premolars were not loaded. After 7 days, premolars were extracted for treatment as indicated. OPG and RANKL mRNA expressions were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and ELISA was used to assess OPG and RANKL protein concentration in compression and tension sides of PDL. Data were subjected to analysis of variance and Tukey tests. RESULTS: There was statistically significant difference in RANKL concentration on comparing control teeth with tension and compression sides of the experimental teeth (P < 0.0001). The expression of mRNA RANKL was increased in the tension and compression sides with 4oz (P < 0.0001). OPG did not show statistically significant association with any group. Changes in RANKL/OPG protein ratio in experimental and control groups showed statistically significant difference (P < 0.0001). CONCLUSIONS: RANKL protein levels are elevated in hPDL loaded with orthodontic forces, suggesting that RANKL protein contributes to bone modeling in response to the initial placement of orthodontic force. PMID- 26823651 TI - Effects of Pseudorabies Virus Infection on the Tracheobronchial Lymph Node Transcriptome. AB - This study represents the first swine transcriptome hive plots created from gene set enrichment analysis (GSEA) data and provides a novel insight into the global transcriptome changes occurring in tracheobronchial lymph nodes (TBLN) and spanning the swine genome. RNA isolated from draining TBLN from 5-week-old pigs, either clinically infected with a feral isolate of Pseudorabies virus or uninfected, was interrogated using Illumina Digital Gene Expression Tag Profiling. More than 100 million tag sequences were observed, representing 4,064,189 unique 21-base sequences collected from TBLN at time points 1, 3, 6, and 14 days post-inoculation (dpi). Multidimensional statistical tests were applied to determine the significant changes in tag abundance, and then the tags were annotated. Hive plots were created to visualize the differential expression within the swine transcriptome defined by the Broad Institute's GSEA reference datasets between infected and uninfected animals, allowing us to directly compare different conditions. PMID- 26823652 TI - Interactive Effects of the BIS and the BAS on Trajectories of Alcohol Misuse after University Graduation. AB - Reinforcement Sensitivity Theory predicts that those with a strong behavioral inhibition system (BIS) likely experience considerable anxiety and uncertainty during the transition out of university. Accordingly, they may continue to drink heavily to cope during this time (a period associated with normative reductions in heavy drinking), but only if they also have a strong behavioral approach system (BAS) to enhance the anxiolytic effects of drinking. The purpose of this study was to test this hypothesis. Participants completed online measures prior to and at 3-month intervals over the course of the year following graduation. As hypothesized, results showed that an elevated BIS predicted impeded maturing out, but only when the impulsivity facet of BAS was also elevated. In contrast, a strong BIS predicted rapid maturing out if BAS impulsivity was weak. Study findings advance our understanding of BIS-related alcohol misuse trajectories in young adulthood and provide direction for clinical interventions. PMID- 26823653 TI - Progesterone After Estradiol Modulates Shuttle-Cage Escape by Facilitating Volition. AB - In animal models of depression, depression is defined as performance on a learning task. That task is typically escaping a mild electric shock in a shuttle cage by moving from one side of the cage to the other. Ovarian hormones influence learning in other kinds of tasks, and these hormones are associated with depressive symptoms in humans. The role of these hormones in shuttle-cage escape learning, however, is less clear. This study manipulated estradiol and progesterone in ovariectomized female rats to examine their performance in shuttle-cage escape learning without intentionally inducing a depressive-like state. Progesterone, not estradiol, within four hours of testing affected latencies to escape. The improvement produced by progesterone was in the decision to act, not in the speed of learning or speed of escaping. This parallels depression in humans in that depressed people are slower in volition, in their decisions to take action. PMID- 26823654 TI - Circulating Neutrophil MicroRNAs as Biomarkers for the Detection of Lung Cancer. AB - Peripheral neutrophils are the predominant circulating leukocytes and an important component of innate and adaptive immune systems, which is a primary defense against cancer. MicroRNAs (miRNAs) can modulate neutrophil functions and play important roles in cancer pathogenesis by regulating neutrophil gene expression. To investigate if assessment of differential miRNA levels of peripheral neutrophils has the potential for diagnosis of non-small-cell lung cancer (NSCLC), we examine neutrophils of 15 patients with stage I NSCLC and 15 smokers without cancer. We identify five neutrophil miRNAs that have an abnormal level in patients with NSCLC versus smokers without cancer. In a training set of 82 patients with lung cancer and 73 controls, a set of two genes (miRs-26a-2-3p and 574-3p) are developed, producing 77.8% sensitivity and 78.1% specificity for NSCLC detection. Furthermore, in a testing set of 60 patients with lung cancer and 58 smokers, the performance of analyzing the two miRNAs for lung cancer detection is confirmed. This study for the first time shows that a neutrophil miRNA profile may serve as a new category of circulating biomarkers for the detection of NSCLC. PMID- 26823656 TI - Institutions of care, moral proximity and demoralisation: The case of the emergency department. AB - This article draws on concepts of morality and demoralisation to understand the problematic nature of relationships between staff and patients in public health services. The article uses data from a case study of a UK hospital Emergency Department to show how staff are tasked with the responsibility of treating and caring for patients, while at the same time their actions are shaped by the institutional concerns of accountability and resource management. The data extracts illustrate how such competing agendas create a tension for staff to manage and suggests that, as a consequence of this tension, staff participate in processes of 'effacement' that limit the presence of patients and families as a moral demand. The analysis from the Emergency Department case study suggests that demoralisation is an increasingly important lens through which to understand health-care institutions, where contemporary organisational cultures challenge the ethical quality of human interaction. PMID- 26823655 TI - Lymphangiogenesis and Lesion Heterogeneity in Interstitial Lung Diseases. AB - The lymphatic system has several physiological roles, including fluid homeostasis and the activation of adaptive immunity by fluid drainage and cell transport. Lymphangiogenesis occurs in adult tissues during various pathologic conditions. In addition, lymphangiogenesis is closely linked to capillary angiogenesis, and the balanced interrelationship between capillary angiogenesis and lymphangiogenesis is essential for maintaining homeostasis in tissues. Recently, an increasing body of information regarding the biology of lymphatic endothelial cells has allowed us to immunohistochemically characterize lymphangiogenesis in several lung diseases. Particular interest has been given to the interstitial lung diseases. Idiopathic interstitial pneumonias (IIPs) are characterized by heterogeneity in pathologic changes and lesions, as typified by idiopathic pulmonary fibrosis/usual interstitial pneumonia. In IIPs, lymphangiogenesis is likely to have different types of localized functions within each disorder, corresponding to the heterogeneity of lesions in terms of inflammation and fibrosis. These functions include inhibitory absorption of interstitial fluid and small molecules and maturation of fibrosis by excessive interstitial fluid drainage, caused by an unbalanced relationship between capillary angiogenesis and lymphangiogenesis and trafficking of antigen-presenting cells and induction of fibrogenesis via CCL21 and CCR7 signals. Better understanding for regional functions of lymphangiogenesis might provide new treatment strategies tailored to lesion heterogeneity in these complicated diseases. PMID- 26823658 TI - Mechanism of Rare Earth Incorporation and Crystal Growth of Rare Earth Containing Type-I Clathrates. AB - Type-I clathrates possess extremely low thermal conductivities, a property that makes them promising materials for thermoelectric applications. The incorporation of cerium into one such clathrate has recently been shown to lead to a drastic enhancement of the thermopower, another property determining the thermoelectric efficiency. Here we explore the mechanism of the incorporation of rare earth elements into type-I clathrates. Our investigation of the crystal growth and the composition of the phase Ba8-x RE x TM y Si46-y (RE = rare earth element; TM = Au, Pd, Pt) reveals that the RE content x is mainly governed by two factors, the free cage space and the electron balance. PMID- 26823657 TI - The Back Squat Part 2: Targeted Training Techniques to Correct Functional Deficits and Technical Factors that Limit Performance. AB - The back squat is a well-researched and widely used exercise to enhance fundamental movement competency that creates a foundation for optimal mechanical strategies during a broad range of activities. The primary commentary introduced the Back Squat Assessment (BSA): a criterion based assessment of the back squat that delineates 30 potentially observable functional deficits. This follow-up commentary provides a targeted system of training cues and exercises to supplement the BSA to guide corrective intervention. We propose a criterion driven approach to corrective exercise that can support practitioners in their goal to help individuals achieve movement competency in the back squat. PMID- 26823659 TI - Regularized Variance Estimation and Variance Stabilization of High Dimensional Data. AB - Among the problems posed by high-dimensional datasets (so called p ? n paradigm) are that variable-specific estimators of variances are not reliable and tests statistics have low powers, both due to a lack of degrees of freedom. In addition, variance is observed to be a function of the mean. We introduce a non parametric adaptive regularization procedure that uses the information contained in the mean to jointly generate local shrinkage estimators of the mean and variance. Regularized t-like statistics derived from these shrinkage estimators have significant more statistical power than their standard sample counterparts, regular common-value shrinkage estimators, or when the information contained in the sample mean is ignored. These estimators feature interesting properties of variance stabilization and normalization that can be used for preprocessing high dimensional multivariate data. PMID- 26823660 TI - Cloning and purification of the first termicin-like peptide from the cockroach Eupolyphaga sinensis. AB - BACKGROUND: Termicin is an antimicrobial peptide with six cysteines forming three disulfide bridges that was firstly isolated from the salivary glands and hemocytes of the termite Pseudacanthotermes spiniger. In contrast to many broad spectrum antimicrobial peptides, termicin is most active against filamentous fungi. Although more than one hundred complementary DNAs (cDNAs) encoding termicin-like peptides have been reported to date, all these termicin-like peptides were obtained from Isoptera insects. METHODS: The cDNA was cloned by combination of cDNA library construction kit and DNA sequencing. The polypeptide was purified by gel filtration and reversed-phase high performance liquid chromatography (RP-HPLC). Its amino acid sequence was determined by Edman degradation and mass spectrometry. Antimicrobial activity was tested against several bacterial and fungal strains. The minimum inhibitory concentration (MIC) was determined by microdilution tests. RESULTS: A novel termicin-like peptide with primary structure ACDFQQCWVTCQRQYSINFISARCNGDSCVCTFRT was purified from extracts of the cockroach Eupolyphaga sinensis (Insecta: Blattodea). The cDNA encoding Es-termicin was cloned by cDNA library screening. This cDNA encoded a 60 amino acid precursor which included a 25 amino acid signal peptide. Amino acid sequence deduced from the cDNA matched well with the result of protein Edman degradation. Susceptibility test indicated that Es-termicin showed strong ability to kill fungi with a MIC of 25 MUg/mL against Candida albicans ATCC 90028. It only showed limited potency to affect the growth of Gram-positive bacteria with a MIC of 200 MUg/mL against Enterococcus faecalis ATCC 29212. It was inactive against gram-negative bacteria at the highest concentration tested (400 MUg/mL). Es-termicin showed high sequence similarity with termicins from many species of termites (Insecta: Isoptera). CONCLUSIONS: This is the first report of a termicin like peptide isolated from E. sinensis that belongs to the insect order Blattodea. Our results demonstrate the diversity of termicin-like peptides, as well as antimicrobial peptides in insects. PMID- 26823661 TI - Application of Microsatellite Loci for Molecular Identification of Elite Genotypes, Analysis of Clonality, and Genetic Diversity in Aspen Populus tremula L. (Salicaceae). AB - Testing systems for molecular identification of micropropagated elite aspen (Populus tremula L.) genotypes were developed on the base on microsatellite (SSR) loci. Out of 33 tested microsatellite loci, 14 were selected due to sustainable PCR amplification and substantial variability in elite clones of aspen aimed for establishment of fast-rotated forest plantations. All eight tested clones had different multilocus genotypes. Among 114 trees from three reference native stands located near the established plantations, 80 haplotypes were identified while some repeated genotypes were attributed to natural clones which appeared as a result of sprouting. The selected set of SSR markers showed reliable individual identification with low probability of appearance of identical aspen genotypes (a minimum of 4.8 . 10(-10) and 1 * 10(-4) for unrelated and related individuals, resp.). Case studies demonstrating practical applications of the test system are described including analysis of clonal structure and levels of genetic diversity in three natural aspen stands growing in the regions where plantations made of elite clones were established. PMID- 26823662 TI - Comparing the Efficacy of Concomitant Therapy with Sequential Therapy as the First-Line Therapy of Helicobacter pylori Eradication. AB - Background. The decline of Helicobacter pylori (H. pylori) eradication rates with standard triple therapy resulted in a search for novel therapies for first-line therapy of H. pylori infection. Aim. The aim of the study is to compare the efficacy of concomitant therapy with sequential therapy as the first-line therapy of H. pylori eradication. Methods. We reviewed medical records of patients who were confirmed to have H. pylori infection and received eradication treatment from September 2012 to March 2015. The concomitant group was treated with rabeprazole, amoxicillin, clarithromycin, and metronidazole for 7 days. The sequential group was treated with rabeprazole and amoxicillin for 5 days and then rabeprazole, clarithromycin, and metronidazole for an additional 5 days. Six weeks after the treatment period, patients in both groups underwent 13C-Urea breath test (UBT) to confirm H. pylori eradication. Results. The eradication rate was 90.3% in the concomitant group and 85.5% in the sequential group. However, the eradication rates between the two groups showed no statistical difference (P = 0.343). Conclusion. No statistical difference was found in eradication rates between the two groups. However, in areas where antibiotic resistance is high, concomitant therapy may be more effective than sequential therapy for H. pylori eradication. PMID- 26823663 TI - Unrevealed Depression Involves Dysfunctional Coping Strategies in Crohn's Disease Patients in Clinical Remission. AB - Background and Aims. This study investigated the proportion of CD patients in clinical remission with clinical depression, and coping strategies in those with severe depressive disorders. Materials and Methods. One hundred consecutive CD patients in clinical remission were screened for anxiety and depression by using Hospital Anxiety and Depression Scale and patients with depressive symptoms were further investigated by means of Cognitive Behavioural Assessment 2.0 and Beck Depression Inventory (BDI). Afterwards the coping strategies were assessed through the Brief-COPE questionnaire. Results. Twenty-one patients had anxious symptoms and 16 had depressive symptoms with or without anxiety. Seven of these patients (43.8%) showed significant depressive symptoms. Compared to patients without psychiatric disorders, these patients showed significant lower score in "positive reframing" (p: 0.017) and in "planning" (p: 0.046) and higher score in "use of instrumental social support" (p < 0.001), in "denial" scale (p: 0.001), and in "use of emotional social support" (p: 0.003). Conclusions. Depressed CD patients in clinical remission may have dysfunctional coping strategies, meaning that they may not be able to implement functional strategies to manage at best stress related with their disease. PMID- 26823664 TI - The Effect of Extremely Low Frequency Alternating Magnetic Field on the Behavior of Animals in the Presence of the Geomagnetic Field. AB - It is known that the geomagnetic field can influence animal migration and homing. The magnetic field detection by animals is known as magnetoreception and it is possible due to two different transduction mechanisms: the first one through magnetic nanoparticles able to respond to the geomagnetic field and the second one through chemical reactions influenced by magnetic fields. Another behavior is the magnetic alignment where animals align their bodies to the geomagnetic field. It has been observed that magnetic alignment of cattle can be disrupted near electric power lines around the world. Experimentally, it is known that alternating magnetic fields can influence living beings, but the exact mechanism is unknown. The parametric resonance model proposes a mechanism to explain that effect on living beings and establishes that, in the presence of a constant magnetic field, molecules associated with biochemical reactions inside cells can absorb resonantly alternating magnetic fields with specific frequencies. In the present paper, a review is made about animal magnetoreception and the effects of alternating magnetic fields in living beings. It is suggested how alternating magnetic fields can interfere in the magnetic alignment of animals and a general conclusion is obtained: alternating magnetic field pollution can affect the magnetic sensibility of animals. PMID- 26823665 TI - Small Cell Carcinoma of the Gallbladder: Case Report and Comprehensive Analysis of Published Cases. AB - Background. Gallbladder small cell carcinoma is a rare and highly aggressive malignancy with no established standard of care treatment. We described here a case report of small cell gallbladder cancer and we then performed a comprehensive review of 72 case reports of this disease. Methods. Published case reports of small cell carcinoma of the gallbladder between 1983 and 2014 were reviewed. Treatment modalities and survival were analyzed for metastatic and localized disease. Results. Median overall survival for all patients was 13 months. Metastatic disease was identified in 72% of cases. Treatment of metastatic disease with chemotherapy showed a significant survival benefit (p < 0.001) compared to no chemotherapy, and the use of platinum doublet with etoposide showed a nonsignificant 4-month improvement in survival compared to other chemotherapy regimens (p = 0.13). Adjuvant therapy did not demonstrate an improvement of median overall survival in local disease (p = 0.78). Conclusion. Given the limited available data, systemic therapy with platinum and etoposide should be considered for patients with metastatic small cell carcinoma of the gallbladder. Adjuvant chemoradiation or chemotherapy for treatment of local disease warrants further investigation. PMID- 26823666 TI - Association between IFN-gamma +874A/T and IFN-gammaR1 (-611A/G, +189T/G, and +95C/T) Gene Polymorphisms and Chronic Periodontitis in a Sample of Iranian Population. AB - Background. Interferon gamma (IFN-gamma) is an immune regulatory cytokine that acts through its receptor and plays important role in progression of inflammatory disease such as chronic periodontitis (CP). The purpose of this study was to determine the differences in the distribution of IFN-gamma (+874A/T) and IFN gammaR1 (-611A/G, +189T/G, and +95C/T) gene polymorphisms among CP and healthy individuals and to investigate relationships between these polymorphisms and susceptibility to CP. Materials and Methods. 310 individuals were enrolled in the study including 210 CP patients and 100 healthy controls. Single nucleotide polymorphisms at IFN-gamma (+874A/T) and IFN-gammaR1 (-611A/G, +189T/G, and +95C/T) were analyzed by ARMS-PCR and PCR-RFLP methods. Results. The significant difference was found in genotype and allele frequency of IFN-gamma (+874A/T) gene polymorphism in chronic periodontitis patients and healthy controls. The distribution of genotypes and allele frequencies for IFN-gammaR1 (-611A/G, +189T/G, and +95C/T) were similar among the groups and no differences in the frequencies of alleles or genotypes of IFN-gammaR1 genetic polymorphisms variants between case and control groups were detected. Conclusion. The finding of this study showed that IFN-gamma +874A/T gene polymorphism may affect susceptibility to CP, whereas IFN-gammaR1 genetic polymorphisms at -611A/G, +189T/G, and +95C/T were not associated with this disease. PMID- 26823667 TI - Generating Diverse Spinal Motor Neuron Subtypes from Human Pluripotent Stem Cells. AB - Resolving the mechanisms underlying human neuronal diversification remains a major challenge in developmental and applied neurobiology. Motor neurons (MNs) represent a diverse pool of neuronal subtypes exhibiting differential vulnerability in different human neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). The ability to predictably manipulate MN subtype lineage restriction from human pluripotent stem cells (PSCs) will form the essential basis to establishing accurate, clinically relevant in vitro disease models. I first overview motor neuron developmental biology to provide some context for reviewing recent studies interrogating pathways that influence the generation of MN diversity. I conclude that motor neurogenesis from PSCs provides a powerful reductionist model system to gain insight into the developmental logic of MN subtype diversification and serves more broadly as a leading exemplar of potential strategies to resolve the molecular basis of neuronal subclass differentiation within the nervous system. These studies will in turn permit greater mechanistic understanding of differential MN subtype vulnerability using in vitro human disease models. PMID- 26823669 TI - Mesenchymal Stromal Cells and Tissue-Specific Progenitor Cells: Their Role in Tissue Homeostasis. AB - Multipotent mesenchymal stromal/stem cells (MSCs) reside in many human organs and comprise heterogeneous population of cells with self-renewal ability. These cells can be isolated from different tissues, and their morphology, immunophenotype, and differentiation potential are dependent on their tissue of origin. Each organ contains specific population of stromal cells which maintain regeneration process of the tissue where they reside, but some of them have much more wide plasticity and differentiate into multiple cells lineage. MSCs isolated from adult human tissues are ideal candidates for tissue regeneration and tissue engineering. However, MSCs do not only contribute to structurally tissue repair but also MSC possess strong immunomodulatory and anti-inflammatory properties and may influence in tissue repair by modulation of local environment. This paper is presenting an overview of the current knowledge of biology of tissue-resident mesenchymal stromal and progenitor cells (originated from bone marrow, liver, skeletal muscle, skin, heart, and lung) associated with tissue regeneration and tissue homeostasis. PMID- 26823668 TI - The Modulatory Effects of Mesenchymal Stem Cells on Osteoclastogenesis. AB - The effect of mesenchymal stem cells (MSCs) on bone formation has been extensively demonstrated through several in vitro and in vivo studies. However, few studies addressed the effect of MSCs on osteoclastogenesis and bone resorption. Under physiological conditions, MSCs support osteoclastogenesis through producing the main osteoclastogenic cytokines, RANKL and M-CSF. However, during inflammation, MSCs suppress osteoclast formation and activity, partly via secretion of the key anti-osteoclastogenic factor, osteoprotegerin (OPG). In vitro, co-culture of MSCs with osteoclasts in the presence of high concentrations of osteoclast-inducing factors might reflect the in vivo inflammatory pathology and prompt MSCs to exert an osteoclastogenic suppressive effect. MSCs thus seem to have a dual effect, by stimulating or inhibiting osteoclastogenesis, depending on the inflammatory milieu. This effect of MSCs on osteoclast formation seems to mirror the effect of MSCs on other immune cells, and may be exploited for the therapeutic potential of MSCs in bone loss associated inflammatory diseases. PMID- 26823671 TI - Allogeneic Platelet Releasate Preparations Derived via a Novel Rapid Thrombin Activation Process Promote Rapid Growth and Increased BMP-2 and BMP-4 Expression in Human Adipose-Derived Stem Cells. AB - The administration of human adipose-derived stem cells (ASCs) represents a promising regenerative therapy for the treatment of orthopedic injuries. While ASCs can be easily isolated from liposuction-derived adipose tissue, most clinical applications will likely require in vitro culture expansion of these cells using nonxenogeneic components. In this study, platelet releasate was generated using a novel rapid thrombin activation method (tPR). ASCs grown in media supplemented with tPR proliferated much faster than ASCs grown in media supplemented with 10% fetal bovine serum. The cells also retained the ability to differentiate along chondrogenic, adipogenic, and osteogenic lineages. The tPR cultured ASCs displayed elevated expression of BMP-4 (5.7 +/- 0.97-fold increase) and BMP-2 (4.7 +/- 1.3-fold increase) and decreased expression of PDGF-B (4.0 +/- 1.4-fold decrease) and FGF-2 (33 +/- 9.0-fold decrease). No significant changes in expression were seen with TGF-beta and VEGF. This pattern of gene expression was consistent across different allogeneic tPR samples and different ASC lines. The use of allogeneic rapidly activated tPR to culture ASCs is associated with both an increased cell yield and a defined gene expression profile making it an attractive option for cell expansion prior to cell-based therapy for orthopedic applications. PMID- 26823670 TI - Endothelial Transdifferentiation of Tumor Cells Triggered by the Twist1-Jagged1 KLF4 Axis: Relationship between Cancer Stemness and Angiogenesis. AB - Tumor hypoxia is associated with malignant biological phenotype including enhanced angiogenesis and metastasis. Hypoxia increases the expression of vascular endothelial cell growth factor (VEGF), which directly participates in angiogenesis by recruiting endothelial cells into hypoxic area and stimulating their proliferation, for increasing vascular density. Recent research in tumor biology has focused on the model in which tumor-derived endothelial cells arise from tumor stem-like cells, but the detailed mechanism is not clear. Twist1, an important regulator of epithelial-mesenchymal transition (EMT), has been shown to mediate tumor metastasis and induce tumor angiogenesis. Notch signaling has been demonstrated to be an important player in vascular development and tumor angiogenesis. KLF4 (Kruppel-like factor 4) is a factor commonly used for the generation of induced pluripotent stem (iPS) cells. KLF4 also plays an important role in the differentiation of endothelial cells. Although Twist1 is known as a master regulator of mesoderm development, it is unknown whether Twist1 could be involved in endothelial transdifferentiation of tumor-derived cells. This review focuses on the role of Twist1-Jagged1/Notch-KLF4 axis on tumor-derived endothelial transdifferentiation, tumorigenesis, metastasis, and cancer stemness. PMID- 26823673 TI - Influence of the Alcohol Present in a Phytotherapic Tincture on Male Rat Lipid Profiles and Renal Function. AB - This study evaluated the influence of the alcohol present in a formulation of the antiophidic phytotherapic tincture, Especifico-Pessoa, on rat blood biochemical and hematological parameters, and on organ histology. Three groups of rats were treated orally for 10, 15, or 30 days; one group received the tincture, the other received alcohol alone, and the third was a control group. The results of this study indicated that cholesterol levels were significantly increased after 10 days in the alcohol and tincture groups, although these decreased after 30 days in the tincture group. Triglyceride levels were significantly reduced after 15 days in the tincture group and after 30 days in the alcohol and tincture groups. A higher creatinine level was observed in the alcohol and tincture groups after 15 and 30 days. The uric acid levels in these groups were reduced at 10 and 30 days, although this metabolite was elevated at 15 days in the alcohol group. Hydropic multifocal degeneration with lymphohistiocytic infiltration and some polymorphonuclear cells was observed in the livers of rats treated with either the tincture or alcohol. These data demonstrate the importance of considering the potential actions of the alcohol present in pharmaceutical formulations. PMID- 26823674 TI - Factor structure of the Chinese version of the geriatric anxiety inventory. AB - BACKGROUND: As China's population ages, the mental health of older people has been increasingly focused on by academic circles. PURPOSE: The aim of this study was to identify the factor structure of the Chinese version of the geriatric anxiety inventory (GAI-CV). METHODS: This study used data collected from Investigation on the anxiety symptoms of the elderly in the city of Beijing supported by scientific research fund project of Renmin University of China. Cronbach's alpha was used to test internal consistency reliability. Both confirmatory and exploratory factor analyses were performed separately for factor analysis. RESULTS: 1318 subjects with mean age 71.35 +/- 7.44 years (male 40.6 %) were involved. Principal components analysis revealed a three-factor structure of the GAI-CV. GAI-CV scales exhibited good internal consistency (Cronbach's alpha = 0.937) and a three-factor model fit the data well [comparative fit index (CFI) = 0.891, root mean square error of approximation (RMSEA) = 0.084]. CONCLUSIONS: The Chinese version of the GAI appears to be reliable and valid to measure anxiety for elderly people in China. PMID- 26823675 TI - Meeting report: GARNet/OpenPlant CRISPR-Cas workshop. AB - Targeted genome engineering has been described as a "game-changing technology" for fields as diverse as human genetics and plant biotechnology. One technique used for precise gene editing utilises the CRISPR-Cas system and is an effective method for genetic engineering in a wide variety of plants. However, many researchers remain unaware of both the technical challenges that emerge when using this technique or of its potential benefits. Therefore in September 2015, GARNet and OpenPlant organized a two-day workshop at the John Innes Centre that provided both background information and hands-on training for this important technology. PMID- 26823676 TI - Erratum to: Use of diffusion magnetic resonance imaging to correlate the developmental changes in grape berry tissue structure with water diffusion patterns. AB - [This corrects the article DOI: 10.1186/1746-4811-10-35.]. PMID- 26823672 TI - The History, Mechanism, and Clinical Application of Auricular Therapy in Traditional Chinese Medicine. AB - Auricular therapy includes acupuncture, electroacupuncture, acupressure, lasering, cauterization, moxibustion, and bloodletting in the auricle. For 2500 years, people have employed auricular therapy for treating diseases, but the methods have been limited to bloodletting and cauterization. Only after 1957, the international scientific community became aware that the map of the ear resembles an inverted fetus, its introduction has led to auricular acupuncture (AA) becoming a more systemic approach, and, following the identification and standardization of more precise points, AA has been employed in clinical applications. The mechanisms of AA are considered to have a close relationship with the autonomic nervous system, the neuroendocrine system, neuroimmunological factors, neuroinflammation, and neural reflex, as well as antioxidation. Auricular therapy has been applied, for example, for pain relief, for the treatment of epilepsy, anxiety, and obesity, and for improving sleep quality. However, the mechanisms and evidence for auricular therapy warrant further study. PMID- 26823677 TI - Revolutionizing plant biology: multiple ways of genome engineering by CRISPR/Cas. AB - The precise manipulation of plant genomes relies on the induction of DNA double strand breaks by site-specific nucleases to initiate DNA repair reactions that are either based on non-homologous end joining (NHEJ) or homologous recombination (HR). Recently, the CRISPR/Cas system emerged as the most important tool for genome engineering due to its simple structure and its applicability to a wide range of organisms. Here, we review the current status of its various applications in plants, where it is used for the successful generation of stable mutations in a steadily growing number of species through NHEJ. Furthermore, tremendous progress in plant genome engineering by HR was obtained by the setup of replicon mediated and in planta gene targeting techniques. Finally, other complex approaches that rely on the induction of more than one DNA lesion at a time such as paired nickases to avoid off-site effects or controlled genomic deletions are beginning to be applied routinely. PMID- 26823678 TI - Neoadjuvant endocrine therapy in breast cancer: current role and future perspectives. AB - Luminal breast cancer, as defined by oestrogen and/or progesterone expression by immunohistochemistry, accounts for up to 75% of all breast cancers. In this population, endocrine therapy is likely to account for most of the gains obtained with the administration of adjuvant systemic treatment. The role of adjuvant chemotherapy in these patients remains debatable since it is known that only a small fraction of patients will derive meaningful benefit from this treatment whilst the majority will be exposed to significant and unnecessary chemotherapy related toxicities, in particular the elderly and frail. Therefore, neoadjuvant endocrine therapy (NET) becomes an attractive option for selected patients with hormonal-receptor positive locally advanced breast cancer. In this review, we discuss the current role of NET and future perspectives in the field. PMID- 26823680 TI - Drug-drug interactions in older patients with cancer: a report from the 15th Conference of the International Society of Geriatric Oncology, Prague, Czech Republic, November 2015. AB - Drugs taken for cancer can interact with each other, with agents taken as part of supportive care, with drugs taken for comorbid conditions (which are particularly common in the elderly patients), and with herbal supplements and complementary medicines. We tend to focus on the narrow therapeutic window of cytotoxics, but the metabolism of tyrosine kinase inhibitors by the cytochrome P450 3A4 enzyme (CYP3A4) makes some TKIs particularly prone to interference with or from other agents sharing this pathway. There is also potential for adverse pharmacokinetic interactions with new hormonal agents used in advanced prostate cancer. PMID- 26823681 TI - Orlando Magic: report from the 57th meeting of the American Society of Haematology, 5-7 December 2015, Orlando, USA. AB - The 57th American Society of Haematology (ASH) meeting held in Orlando, FL was certainly the year when myeloma management changed for good, with a plethora of newly Food and Drug Administration (FDA)-approved drugs showing impressive outcome improvements and the introduction of new techniques for disease monitoring. Also, chimeric antigen receptor (CAR) T cells continued their triumphal march, consolidating their success in lymphoma and chronic lymhocytic leukaemia (CLL) and venturing into new fields such as again multiple myeloma. Some experimental drugs showed long-awaited results (midostaurin in FLT3-mutated acute myeloid leukaemia (AML)) and some brand new drugs showed promising results in the clinic after extensive preclinical studies, such as those targeting new epigenetic factors (histone methyltransferases) and apoptosis. PMID- 26823679 TI - Repurposing Drugs in Oncology (ReDO)-diclofenac as an anti-cancer agent. AB - Diclofenac (DCF) is a well-known and widely used non-steroidal anti-inflammatory drug (NSAID), with a range of actions which are of interest in an oncological context. While there has long been an interest in the use of NSAIDs in chemoprevention, there is now emerging evidence that such drugs may have activity in a treatment setting. DCF, which is a potent inhibitor of COX-2 and prostaglandin E2 synthesis, displays a range of effects on the immune system, the angiogenic cascade, chemo- and radio-sensitivity and tumour metabolism. Both pre clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. Based on this evidence the case is made for further clinical investigation of the anticancer effects of DCF, particularly in combination with other agents - with a range of possible multi-drug and multi-modality combinations outlined in the supplementary materials accompanying the main paper. PMID- 26823682 TI - Utility of endometrial sampling prior to risk-reducing hysterectomy in a patient with Lynch syndrome. AB - Occult endometrial cancer is occasionally discovered in women with Lynch syndrome undergoing risk-reducing hysterectomy. The case presented here demonstrates that preoperative endometrial sampling can help detect these occult cancers; however, there are currently no recommendations for this preoperative intervention. A 50 year-old woman with Lynch syndrome underwent endometrial sampling prior to planned risk-reducing hysterectomy and bilateral salpingo-oophorectomy. The endometrial biopsy demonstrated a serous endometrial cancer. The patient was counselled regarding the diagnosis and revised operative plan, which now included staging, prior to surgery. Although the prevalence of occult endometrial cancer at the time of risk-reducing surgery in women with Lynch syndrome remains unknown, preoperative endometrial sampling may allow for improved patient counselling and surgical planning in this population, and can help avoid a subsequent surgery for staging. PMID- 26823683 TI - Socioeconomic differentials and mortality from colorectal cancer in large cities in Brazil. AB - The objective of this study was to compare the mortality pattern of colorectal cancer according to the social development profile of the large Brazilian cities. This was an ecological study that used as units of analysis Brazilian municipalities that were considered to be large (i.e. over 100,000 inhabitants). The social indicators adopted were obtained from the Atlas of Human Development in Brazil. Mortality data came from the Mortality Information System (MIS), represented by codes C18, C19, and C20. For data analysis, municipalities were characterised according to the indicator profile used by multivariate classification cluster analysis. It was observed that the Southeast, South, and Midwest regions concentrated over 90% of cities in the group of more developed municipalities, while the North and Northeast regions were represented by 60% of cities in the group of less developed municipalities. The mortality pattern of colorectal cancer in both groups was different, with a higher average mortality rate from colorectal cancer for populations living in cities from the more developed group (p = 0.02). The mortality rate from this cancer was shown to be directly proportional to the Municipal Human Developlemnt Index (MHDI) and inversely proportional to the inequality indicator (p < 0.001); therefore the highest means were observed among the municipalities with better socioeconomic conditions. It is important to consider social disparities to ensure equity in healthcare policy management. PMID- 26823684 TI - Highlights of the eleventh annual meeting of the National Cancer Research Institute, 1-4 November 2015, Liverpool, UK. AB - The annual meeting of the National Cancer Research Institute (NCRI), held in Liverpool, UK, has a solid reputation of being a multidisciplinary conference. It brings the diverse cancer interests of the United Kingdom together, from funders to researchers to clinicians. Key themes for the coming year's innovation emerge. At this meeting, particularly notable topics were immunotherapy and prevention, with sessions on Big Data and e-cigarettes generating significant interest and discussion. Broad themes included discussions around cancer evolution, and the economic challenges of the United Kingdom's cancer burden. PMID- 26823685 TI - Does cancer research focus on areas of importance to patients? AB - The majority of research ideas are proposed by clinicians or scientists and little is currently known about which areas of research patients feel are important. We performed a 4 week pilot patient survey at the Royal Marsden (a specialist cancer centre) to investigate patients' views on priorities for cancer research. A total of 780 patients completed the survey and the top research priorities were identified as: detection and prevention of cancer, scientific understanding, curative treatment and personalised treatment. The top research priorities were remarkably consistent across age, gender and a variety of tumour types. We believe that patients' views should be considered alongside those of clinicians and researchers when devising research proposals and strategies. PMID- 26823687 TI - What happens to the motor theory of perception when the motor system is damaged? AB - Motor theories of perception posit that motor information is necessary for successful recognition of actions. Perhaps the most well known of this class of proposals is the motor theory of speech perception, which argues that speech recognition is fundamentally a process of identifying the articulatory gestures (i.e. motor representations) that were used to produce the speech signal. Here we review neuropsychological evidence from patients with damage to the motor system, in the context of motor theories of perception applied to both manual actions and speech. Motor theories of perception predict that patients with motor impairments will have impairments for action recognition. Contrary to that prediction, the available neuropsychological evidence indicates that recognition can be spared despite profound impairments to production. These data falsify strong forms of the motor theory of perception, and frame new questions about the dynamical interactions that govern how information is exchanged between input and output systems. PMID- 26823686 TI - Somatic/gonadal mosaicism for structural autosomal rearrangements: female predominance among carriers of gonadal mosaicism for unbalanced rearrangements. AB - BACKGROUND: Mosaicism for chromosomal structural rearrangements (Rea) is rare and the timing and mechanisms of mosaic Rea formation, maintenance, and clinical manifestation are poorly understood. To date, there are no published data on the cytogenetic profile of mosaic Reas. The question as to whether the proportion of abnormal cells in the carrier's cultured blood is clinically significant remains unanswered. A previous study showed a strong female preponderance among carriers of mosaicism for Rea with pericentromeric breaks, indicating female-specific instability in early embryos. However, there is no corresponding study on male to female sex ratio (SR) among carriers of somatic and/or gonadal mosaicism for non centromeric Rea. Population rates of mosaic Rea carriers calculated from consecutive series of patients referred for various reasons and from prenatal samples have not been established. Therefore the objectives of the present study were several-fold: (1) a study on profiles of Rea involved, (2) comparative analysis of the proportion of cells with unbalanced Rea in blood cultures from asymptomatic and affected carriers, (3) comparative analysis of SR in carriers of mosaicism for balanced and unbalanced Rea, and (4) determination of the population frequency of mosaicism for autosomal Rea. RESULTS: One hundred and three cases of mosaicism for autosomal non-centromeric Rea (N/Rea; normal line/structural rearrangement) in which the sex of the carrier had been specified were identified in the literature. Among balanced Rea, there was a prevalence of reciprocal translocations (89 %) over inversions (11 %). Among unbalanced Rea, deletions were the most frequent (40 %), followed by duplications (25 %) and rings (16 %). Derivatives and other chromosome abnormalities were less frequent (9 and 10 %). Eight of eleven (73 %) affected carriers of unbalanced Rea displayed a high proportion (>50 %) of abnormal cells compared to 4/37 (11 %) in asymptomatic carriers, p < 0.0001. Among carriers of mosaicism for balanced Rea there was a slight male predominance, 24 M/22 F, unlike the strong female predominance among carriers of mosaicism for unbalanced Rea, 11 M/46 F, p < 0.0001. Among ten carriers of unbalanced Rea with reproductive failure, only one was a male with infertility, and one was a partner of a woman experiencing recurrent spontaneous abortion. Population rates of mosaics for reciprocal translocaton (N/rcp), inversion (N/inv), and unbalanced Rea (N/unbal Rea) calculated from published data on consecutive series of patients with reproductive failures were 0.02 0/00, 0.005 0/00, and 0.002 0/00, correspondingly. Among 30,376 infertile patients three carriers of mosaicism for balanced Rea were identified (two cases of N/rcp and one case of N/inv), whereas among 26,384 patients with habitual abortion seven carriers were detected (five N/rcp and two N/inv). Among all 56,760 tested patients with reproductive failures only one was found to be a carrier of mosaicism for an unbalanced Rea (N/del, mosaicism for deletion). CONCLUSIONS: A high proportion of Rea cells (>50 %) detected in cultured T-lymphocytes is associated with clinical manifestation of chromosomal imbalance. A strong female prevalence among carriers of mosaicism for unbalanced Rea suggests male-specific selection against abnormal cells rather than impairment of male gametogenesis, as the latter suggests a better prognosis for male fetuses. These findings should be taken into consideration when genetic counseling of patients referred after a diagnosis of mosaicism for an unbalanced rearrangement in a fetus. PMID- 26823688 TI - Insulin-like growth factor axis in pregnancies affected by fetal growth disorders. AB - BACKGROUND: Insulin-like growth factors 1 and 2 (IGF1 and IGF2) and their binding proteins (IGFBPs) are expressed in the placenta and known to regulate fetal growth. DNA methylation is an epigenetic mechanism which involves addition of methyl group to a cytosine base in the DNA forming a methylated cytosine phosphate-guanine (CpG) dinucleotide which is known to silence gene expression. This silences gene expression, potentially altering the expression of IGFs and their binding proteins. This study investigates the relationship between DNA methylation of components of the IGF axis in the placenta and disorders in fetal growth. Placental samples were obtained from cord insertions immediately after delivery from appropriate, small (defined as birthweight <10th percentile for the gestation [SGA]) and macrosomic (defined as birthweight > the 90th percentile for the gestation [LGA]) neonates. Placental DNA methylation, mRNA expression and protein levels of components of the IGF axis were determined by pyrosequencing, rtPCR and Western blotting. RESULTS: In the placenta from small for gestational age (SGA) neonates (n = 16), mRNA and protein levels of IGF1 were lower and of IGFBPs (1, 2, 3, 4 and 7) were higher (p < 0.05) compared to appropriately grown neonates (n = 37). In contrast, in the placenta from large for gestational age (LGA) neonates (n = 20), mRNA and protein levels of IGF1 was not different and those of IGFBPs (1, 2, 3 and 4) were lower (p < 0.05) compared to appropriately grown neonates. Compared to appropriately grown neonates, CpG methylation of the promoter regions of IGF1 was higher in SGA neonates. The CpG methylation of the promoter regions of IGFBP1, IGFBP2, IGFBP3, IGFBP4 and IGFBP7 was lower in the placenta from SGA neonates as compared to appropriately grown neonates, but was unchanged in the placenta from LGA neonates. CONCLUSIONS: Our results suggest that changes in CpG methylation contribute to the changes in gene expression of components of the IGF axis in fetal growth disorders. Differential methylation of the IGF1 gene and its binding proteins is likely to play a role in the pathogenesis of SGA neonates. PMID- 26823689 TI - The cardiovascular and hypothalamus-pituitary-adrenal axis response to stress is controlled by glucocorticoid receptor sequence variants and promoter methylation. AB - BACKGROUND: Gender, genetic makeup, and prior experience interact to determine physiological responses to an external perceived stressor. Here, we investigated the contribution of both genetic variants and promoter methylation of the NR3C1 (glucocorticoid receptor) gene to the cardiovascular and hypothalamus-pituitary adrenal (HPA) axis response to the socially evaluated cold pressor test (seCPT). RESULTS: Two hundred thirty-two healthy participants were recruited and underwent the experiment. They were randomly assigned to either the seCPT group (cold water) or a control group (warm water). The seCPT group had a clear stress reaction; salivary cortisol levels and peak systolic and diastolic blood pressure all increased significantly compared to the control group. GR genotype (TthIIII, NR3C1-I, 1H, E22E, R23K, BclI and 9beta) and methylation data were obtained from 218 participants. Haplotypes were built from the GR genotypes, and haplotype 2 (minor allele of BclI) carriers had a higher cortisol response to the seCPT in comparison to non-carriers (20.77 +/- 13.22; 14.99 +/- 8.42; p = 0.034), as well as independently of the experimental manipulation, higher baseline heart rate (72.44 +/- 10.99; 68.74 +/- 9.79; p = 0.022) and blood pressure (115.81 +/- 10.47; 111.61 +/- 10.74; p = 0.048). Average methylation levels throughout promoter 1F and 1H were low (2.76 and 1.69 %, respectively), but there was a strong correlation between individual CpGs and the distance separating them (Pearson's correlation r = 0.725, p = 3.03 * 10(-26)). Higher promoter-wide methylation levels were associated with decreased baseline blood pressure, and when incorporated into a linear mixed effect model significantly predicted lower systolic and diastolic blood pressure evolution over time in response to the experimental manipulation. The underlying genotype significantly predicted methylation levels; particularly, the homozygous BclI minor allele was associated with higher methylation in promoter 1H (p = 0.042). CONCLUSIONS: This is one of the first studies linking epigenetic modifications of the GR promoter, receptor genotype and physiological measures of the stress response. At baseline, there were clear genetic and epigenetic effects on blood pressure. The seCPT induced a strong cardiovascular and HPA axis response, and both systems were affected by the functional genetic variants, although methylation also predicted blood pressure reactivity. The return to baseline was predominantly influenced by the genomic sequence. Overall, the physiological response to the seCPT is controlled by an exquisite mix of genetic and epigenetic factors. PMID- 26823690 TI - Epigenetic associations of type 2 diabetes and BMI in an Arab population. AB - BACKGROUND: The prevalence of type 2 diabetes (T2D) and obesity has dramatically increased within a few generations, reaching epidemic levels. In addition to genetic risk factors, epigenetic mechanisms triggered by changing environment are investigated for their role in the pathogenesis of these complex diseases. Epigenome-wide association studies (EWASs) have revealed significant associations of T2D, obesity, and BMI with DNA methylation. However, populations from the Middle East, where T2D and obesity rates are highest worldwide, have not been investigated so far. METHODS: We performed the first EWAS in an Arab population with T2D and BMI and attempted to replicate 47 EWAS associations previously reported in Caucasians. We used the Illumina Infinium HumanMethylation450 BeadChip to quantify DNA methylation in whole blood DNA from 123 subjects of 15 multigenerational families from Qatar. To investigate the effect of differing genetic background and environment on the epigenetic associations, we further assessed the effect of replicated loci in 810 twins from UK. RESULTS: Our EWAS suggested a novel association between T2D and cg06721411 (DQX1; p value = 1.18 * 10(-9)). We replicated in the Qatari population seven CpG associations with BMI (SOCS3, p value = 3.99 * 10(-6); SREBF1, p value = 4.33 * 10(-5); SBNO2, p value = 5.87 * 10(-5); CPT1A, p value = 7.99 * 10(-5); PRR5L, p value = 1.85 * 10(-4); cg03078551, intergenic region on chromosome 17; p value = 1.00 * 10(-3); LY6G6E, p value = 1.10 * 10(-3)) and one with T2D (TXNIP, p value = 2.46 * 10(-5)). All the associations were further confirmed in the UK cohort for both BMI and T2D. Meta-analysis increased the significance of the observed associations and revealed strong heterogeneity of the effect sizes (apart from CPT1A), although associations at these loci showed concordant direction in the two populations. CONCLUSIONS: Our study replicated eight known CpG associations with T2D or BMI in an Arab population. Heterogeneity of the effects at all loci except CPT1A between the Qatari and UK studies suggests that the underlying mechanisms might depend on genetic background and environmental pressure. Our EWAS results provide a basis for comparison with other ethnicities. PMID- 26823691 TI - Utilization of the clinical laboratory for the implementation of concussion biomarkers in collegiate football and the necessity of personalized and predictive athlete specific reference intervals. AB - BACKGROUND: A continued interest in concussion biomarkers makes the eventual implementation of identified biomarkers into routine concussion assessment an eventual reality. We sought to develop and test an interdisciplinary approach that could be used to integrate blood-based biomarkers into the established concussion management program for a collegiate football team. METHODS: We used a CLIA-certified laboratory for all testing and chose biomarkers where clinically validated testing was available as would be required for results used in clinical decision making. We summarized the existing methods and results for concussion assessment across an entire season to identify and demonstrate the challenges with the eventual integration of a parallel process using blood-based tests for concussion management. We analyzed the results of the biomarkers chosen for trends consistent with the outcome assessments provided from the current concussion management protocols. RESULTS: Baseline samples were collected with three additional post-concussion samples collected at three separate time points from players with a diagnosed concussion (n = 12). A summary of results from currently used concussion assessment tools were compared to the representative biomarkers S100B and NSE results. Nine sport-related concussions occurred during practice and three during play. For S100B, 50 % had follow-up testing results lower than the post-injury result. In contrast, 92 % of NSE follow-up results were lower than post-injury. One hundred percent of the results for S100B and NSE were within the athlete-derived reference intervals upon return-to-play and season end. CONCLUSIONS: The reported workflow provides a framework for the eventual implementation of biomarkers for concussion assessment into existing assessment protocols and strengthens the need for reliance on clinical laboratory testing. Athlete-specific reference intervals will be required to adequately interpret results. PMID- 26823692 TI - Killing effect of TNF-mediated by conditionally replicating adenovirus on esophageal cancer and lung cancer cell lines. AB - OBJECTIVE: The killing effect of TNF mediated by conditionally replicating adenovirus SG502 on human cancer cell lines was assessed by in vivo and in vitro experiments. METHODS: The recombinant adenovirus SG502-TNF was used to infect human lung cancer cell line A549 and human esophageal cancer cell line TE-1. The expression of the exogenous gene and its inhibitory effect on the tumor cell lines were thus detected. Tumor transplantation experiment was performed in mice with the purpose of assessing the inhibitory effect of the adenovirus on tumor cells and tumor formation. The targeting of the adenovirus and the mechanism of tumor inhibition were discussed by in vivo imaging technology, HE staining and TUNEL assay. RESULTS: Recombinant adenovirus SG502-TNF targeted the tumor cells specifically with stable expression of TNF, which produced a killing effect on tumor cells by regulating the apoptotic signaling pathway. CONCLUSION: Recombinant adenovirus SG502-TNF possessed significant killing effect on TE-1 cells either in vivo or in vitro. This finding demonstrated the potential clinical application of adenovirus SG502. PMID- 26823693 TI - Effect of tumor-associated macrophages on gastric cancer stem cell in omental milky spots and lymph node micrometastasis. AB - We observed whether the effect of tumor-associated macrophages on gastric cancer stem cell in omental milky spots and lymph nodes micrometastasis and research its possible mechanism. Macrophage THP-1 cells and Human gastric adenocarcinoma SGC 7901 cells were collectively cultivated in vivo. We found macrophage could suppress the proliferation and accelerated cell death of MFC cell. Meanwhile, these effects may be concerned with many signaling pathways, and we detected MCP 1 and COX-2 miRNA expressions, PGE-2 release levels, IL-4 and IL-10 activities, and TGF-beta, IFN-gamma, VEGF, MMP-2 and MMP-9 protein expressions in collectively cultivated cell. We found that MCP-1 and COX-2 miRNA expressions, and PGE-2 release levels were suppressed, IL-4 activity was inhibited and IL-10 activity was activated in collectively cultivated cell. Meanwhile, TGF-beta, MMP 2 and MMP-9 protein expressions were inhibited and IFN-gamma and VEGF protein expressions were activated in collectively cultivated cell. Taken together, these results suggest that the effect of tumor-associated macrophages on gastric cancer stem cell in omental milky spots and lymph nodes micrometastasis via COX-2/PGE 2/TGF-beta/VEGF signal pathways. PMID- 26823694 TI - Influence of interleukin-1 beta gene polymorphisms on the risk of myocardial infarction and ischemic stroke at young age in vivo and in vitro. AB - In this study, by using vivo and vitro model, we assessed whether interleukin (IL)-1beta gene polymorphisms influence on the risk of myocardial infarction and ischemic stroke at young age. 147 patients (age < 45 years) with a first episode of MI and 56 patients (age < 45 years) with first-ever cerebral ischemia consecutively were admitted to this study from the Department of Chinese PLA General Hospital. Meanwhile, 91 normal volunteers without MI or stroke were deeded as control group and greed to give blood samples for DNA analysis and biochemical measurements by written informed consent. IL-1beta-511 wild type (WT, CC) and SNP (TT) were established and transfected into Rat myocardial H9c2 cell and Mouse brain endothelial bEND.3 cells. In Young Age MI or stroke patients, the IL-1beta levels of patients with 511CC are higher than that of patients with 511TT. In our study, NF-kappaB miRNA, iNOS activity, NF-kappaB, iNOS and Bax protein expressions of MI-induced H9c2 cell or stroke-induced bEND.3 cells in IL 1beta-511TT group were lower than those of IL-1beta-511CC. Additionally, the protein expression of MMP-2 of MI-induced H9c2 cell or stroke-induced bEND.3 cells in IL-1beta-511TT group were higher than that of IL-1beta 511CC group. In conclusion, our data indicate that IL-1beta-511TT/CC influence on the risk of myocardial infarction and ischemic stroke at young age through NF-kappaB, iNOS, MMP-2 and Bax. PMID- 26823695 TI - Spindle cell/sclerosing rhabdomyosarcoma: case series from a single institution emphasizing morphology, immunohistochemistry and follow-up. AB - Spindle cell/sclerosing rhabdomyosarcoma is a rare skeletal-muscle tumor with distinctive clinicopathologic characteristics. 10 cases (6 cases of spindle cell rhabdomyosarcoma and 4 cases of scleroisng rhabdomyosarcoma) were composed of 6 males and 4 females aging from 5 months to 57 years, with median age 33 years, most of who represented a painless solid mass. Histologically, the tumors were composed of fascicles of spindle cells or primitive round cells embed in sclerotic matrix with presence of rhabdomyoblasts in varying proportion. Immunohistochemically, the tumor cells expressed MyoD1 (10/10), Desmin (10/10), myogenin (6/10), AE1/AE3 (2/10), EMA (2/10), but were negative for SMA, caldesmon, S-100. All of the patients underwent a complete surgical resection without or with chemotherapy (2/10) or radiotherapy (1/10). During the follow-up period (1 to 24 months), 1 patient was succumbed, and 2 cases showed in situ recurrence with 1 of them adopting metastasis. Our cases further demonstrate there do present some clincopathologic relations between spindle cells rhabdomyosarcoma and sclerosing rhabdomyosarcoma, but the latter seems to have a better prognosis. Exact grading and staging contribute to predict the outcome. PMID- 26823696 TI - Wortmannin, PI3K/Akt signaling pathway inhibitor, attenuates thyroid injury associated with severe acute pancreatitis in rats. AB - Increasing evidences suggest that PI3K/AKT pathway plays an important role in the pathogenesis of inflammatory diseases such as acute pancreatitis. However, the exact effect of PI3K/AKT on thyroid injury associated with acute pancreatitis has not been investigated. This study aimed to investigate the protective effects of wortmannin, PI3K/AKT inhibitor, on thyroid injury in a rat model of severe acute pancreatitis (SAP). Sixty male SD rats were randomly divided into four groups: sham operating group (SO), SAP group, wortmannin treatment (WOR) group and drug control (WOR-CON) group. Serum amylase (AMY), lipase (LIP) and thyroid hormone levels were evaluated. The morphological change of thyroid tissue was analyzed under the light and transmission electron microscopy. AKT, P38MAPK and NF-kappaB expression in the thyroid tissue was evaluated by immunohistochemical staining. Oxidative stress and inflammatory cytokines were detected. Results showed that wortmannin attenuated the following: (1) serum AMY, LIP and thyroid hormone (2) pancreatic and thyroid pathological injuries (3) thyroid MDA, (4) thyroid ultrastructural change, (5) serum TNF-alpha, IL-6 and IL-1beta (6) AKT, MAPKP38 and NF-kappaB expression in thyroid tissues. These results suggested that wortmannin attenuates thyroid injury in SAP rats, presumably because of its role on prevent ROS generation and inhibits the activation of P38MAPK, NF-kappaB pathway. Our findings provide new therapeutic targets for thyroid injury associated with SAP. PMID- 26823697 TI - Mixed group of Rhizobiales microbes in lung and blood of a patient with fatal pulmonary illness. AB - We examined the microbial composition in the diseased lung and early-phase microbial cultures from the blood of a patient with a rapidly progressing fatal pulmonary illness. Although no microbes could be isolated from such cultures during the initial study, the HTS-microbiome study revealed the presence of a unique mixture of alphaproteobacteria, composed mainly of different families of Rhizobiales microbes. Microbial 16S rDNA sequences matching closely to Afipia cberi were identified mainly in the patient's diseased lung tissue, but only rarely in the early-phase blood cultures. Conversely, the high abundance of sequences found in early-phase blood cultures of different broth media matched closely with those of the families Methylobacteriaceae, Phyllobacteriaceae and Sphingomonadaceae. The two species that successfully adapted to grow in a laboratory culture system were A. cberi and Mesorhizobium hominis, which eventually were isolated from a previously cryopreserved blood culture of SP4 broth. Many other species, including members of the Bradyrhizobiaceae and Phyllobacteriaceae families, and all members of the Methylobacteriaceae and Sphingomonadaceae families identified by HTS remained non-cultivated. We developed specific PCR primers and FISH probes, which detected the target Rhizobiales microbes in former blood cultures and autopsy lung tissues. It is unclear what role these Rhizobiales microbes might have played in the patient's complex disease process. However, the above mentioned assays should help in rapidly detecting and identifying these previously unrecognized Rhizobiales microbes in patients. PMID- 26823698 TI - MicroRNA-377 inhibits non-small-cell lung cancer through targeting AEG-1. AB - Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related deaths. MicroRNAs (miRNAs) have been reported to be involved in tumorigenesis. However, the underlying mechanisms of microRNA-377 (miR-377) in NSCLC remain unknown. Hence, in the present study, we aimed to explore the role of miR-377 in the development of NSCLC, with identifying its target genes. The results showed that miR-377 expression was significantly decreased in NSCLC tissues as well as in NSCLC cell lines. Moreover, high expression of miR-377 could markedly inhibit the viability, proliferation, migration and invasion of NSCLC cells. The bioinformatics analysis results showed that astrocyte elevated gene-1 (AEG-1), an oncogene as previously reported, was a potential target gene of miR-377, which was further validated by dual-luciferase reporter assay. Besides, the expression of AEG-1 in protein level was decreased by miR-377 overexpression, but not in mRNA level. In addition, AEG-1 overexpression could reverse the inhibitory effects on NSCLC cells caused by miR-377 transfection. In conclusion, our results suggested that miR-377 played an important role in the development of NSCLC by regulating AEG-1 and may be a potential therapeutic target for NSCLC. PMID- 26823699 TI - Oleanolic acid suppresses the proliferation of human bladder cancer by Akt/mTOR/S6K and ERK1/2 signaling. AB - Oleanolic acid has significant pharmacological activities, such as anti-tumor, regulating blood sugar level and liver protection, which are more effective compared with free aglyconeoleanolic acid. However, it is still unknown if oleanolic acid affects the proliferation of human bladder cancer. We utilized T24 cells to study the effect of oleanolic acid on the proliferation and apoptosis of human bladder cancer. In this study, we found that the anti-cancer effect of oleanolic acid significantly suppressed cell proliferation and increased apoptosis and caspase-3 activity of T24 cells. Furthermore, Akt, mTOR and S6K protein expression was greatly inhibited in T24 cells under oleanolic acid treatment. Meanwhile, ERK1/2 of phosphorylation protein expression was significantly promoted by oleanolic acid treatment. Taken together, we provided evidences that oleanolic acid was Akt/mTOR/S6K and ERK1/2 signaling-targeting anti-tumor agent. These findings represent new evidences that oleanolic acid suppresses the proliferation of human bladder cancer by Akt/mTOR/S6K and ERK1/2 signaling, and oleanolic acid may be used to prevent human bladder cancer. PMID- 26823700 TI - Cellular transcriptomics: gelsolin negatively regulates the expression of apoptosis-associated genes and inhibits apoptosis in hepatocarcinoma cells. AB - Gelsolin (GSN), which is a Ca(2+)-dependent actin filament severing and capping protein, plays a critical role in the cancer progress and has the potential for providing a novel thread for cancer therapy. In current study, we demonstrate the roles of GSN on anti-apoptosis of hepatocarcinoma cells by transcriptome RNA-seq method. Then flow cytometry (FCM), in-cell immunoblotting and transmission electron microscopy (TEM) were used to examine the GSN regulatory cell apoptosis. The results revealed GSN significantly suppresses apoptosis-associated functional categories through down-regulating apoptosis-associated genes in 5 apoptosis terms and 6 relevant KEGG pathways. FCM showed a significant lower apoptotic rate in GSN-SMMC7721 (P<0.05). In-cell immunoblotting detected discrepant expression of the apoptosis factors among GSN expressed/shRNA transfectants (P<0.05). TEM observed the discernible apoptosis morphology. Above results suggest a negative relationship between GSN expression and hepatocarcinoma cell apoptosis. GSN overexpression suppresses apoptosis while down-regulated GSN promotes apoptosis. The possible mechanism could be associated with the regulation of GSN on the apoptosis-associated pathways and the apoptosis factors caspase 3 and bcl-2. PMID- 26823701 TI - Zinc finger protein x-linked (ZFX) contributes to patient prognosis, cell proliferation and apoptosis in human laryngeal squamous cell carcinoma. AB - Zinc finger protein, X-linked (ZFX) gene locus on the human X chromosome is structurally similar to the zinc finger protein, Y-linked gene. Its role in human laryngeal squamous cell carcinoma (LSCC) is still not clearly defined. This study was focused on investigating the role of zinc-finger protein X-linked (ZFX) in human LSCC. Expression levels of ZFX were examined in LSCC tissues, corresponding adjacent non-tumoral tissues and vocal leukoplakia tissues by immunohistochemistry (IHC). The association with the expression level of ZFX and LSCC clincopathological parameters was analyzed. The prognostic value of ZFX expression was also analyzed. Lentivirus-mediated RNA interference was applied to silence ZFX expression and the effects of ZFX knockdown on the growth of human LSCC primary cells was investigated. Overexpression of ZFX was found in LSCC tissues. The expression of ZFX was associated with the clinical stage of LSCC. Patients with higher level of ZFX experienced a poorer prognosis compared to those with lower level of ZFX. Knockdown of ZFX inhibited cell proliferation, colony formation and migration of LSCC primary cells. Moreover, ZFX silencing induced cell apoptosis. These results provide the convincing evidence for the first time that ZFX plays an important role in LSCC development and could be a potential therapeutic target or prognostic predictor for LSCC. PMID- 26823702 TI - A possible complementary tool for diagnosing tuberculosis: a feasibility test of immunohistochemical markers. AB - Differentiation of tuberculous granuloma (TG) from non-tuberculous granuloma (NG) is histopathologically difficult. We evaluated the usefulness of selected immunohistochemical markers to differentiate tuberculous granuloma (TG) and non tuberculous granuloma (NG). We selected six biomarkers (FoxP3, TNF-beta, E selectin [ESEL], indoleamine 2,3-dioxygenase [IDO], lactoferrin [LACT], and tartrate-resistant acid phosphatase [TRAP]) and immunohistochemically analyzed their expression in the presence of two types of granulomatous tissue samples, TG (n = 36) and NG (n = 31), using a microarray format. Three of those six biomarkers (LACT, IDO, and TNF-beta) were moderately accurate in discriminating TG from NG, individually and in combination, according to ROC analysis (AUC = 0.7 0.89, sensitivity = 55.6-77.8%, specificity = 71.0-100%). Our data indicate that selected immunohistochemical markers (LACT, IDO, and TNF-beta) can be used in ancillary tests to differentiate TG from NG in tissue samples. Further large scale studies are required to validate our results. PMID- 26823703 TI - Morphological changes in the sciatic nerve, skeletal muscle, heart and brain of rabbits receiving continuous sciatic nerve block with 0.2% ropivacaine. AB - OBJECTIVE: To investigate the morphological changes in various tissues of rabbits receiving sciatic nerve block with 0.2% ropivacaine for 48 h. METHODS: Twenty healthy were randomly assigned to normal saline group (N group) and ropivacaine group (R group). The right sciatic nerve was exposed, and a nerve-blocking trocar cannula embedded. Animals received an injection of 0.5% ropivacaine hydrochloride at a dose of 0.75 ml/kg. Rabbit was then connected to an infusion pump containing 50 ml of normal saline in N group, or to a infusion pump containing 0.2% ropivacaine hydrochloride in R group at 0.25 ml/kg*h-1. RESULTS: In both R group and N group, a small number of nerve cells exhibited pyknotic degeneration. More nerve cells with pyknotic degeneration were found in R group than in N group (P<0.001). At 48 h after surgery, there was a significant correlation between the abnormality of right hind limb and the degree of edema in sciatic nerve (P<0.01). CONCLUSION: Pyknotic degeneration of sciatic nerve increased after an infusion of 0.2% ropivacaine hydrochloride for 48 h, suggesting the neurotoxicity of ropivacaine. An infusion of 0.2% ropivacaine hydrochloride for 48 h may cause necrosis of skeletal muscle cells. The sciatic nerve edema would greatly affect the hindlimb motor while both pyknotic degeneration of sciatic nerve and skeletal muscle have little influence on the hindlimb movement. After an infusion of 0.2% ropivacaine hydrochloride for 48 h, the morphology of right atrium and brain tissues around the ventriculus tertius and medulla oblongata remained unchanged. PMID- 26823704 TI - Inhibition of LN-308 glioma cell proliferation and migration by retinoic acid amide through activation of Akt pathway. AB - The present study was performed to investigate the effect of retinoic acid amide (RAA) on the expression of integrin alpha3beta1, rate of cell proliferation and migration in p53-deficient glioma cell line, LN-308. The results revealed promotion of integrin alpha3 expression, reduction in proliferation and migration in RAA treated cells compared to the control LN-308 glioma cells. Promotion of RAA induced integrin alpha3beta1 expression led to the enhancement in cyclin dependent kinase nuclear localization and activation of Akt pathway. In addition, RAA treatment inhibited the expression of nuclear factor-kappaB, Bcl-2 and epidermal growth factor receptor (EGFR). These factors are responsible for promoting the rate of cell proliferation and survival in the carcinoma cells. Thus RAA treatment inhibits rate of LN-308 glioma cell proliferation and migration through increase in integrin alpha3beta1 expression and activation of Akt pathway. Therefore, RAA can be of therapeutic importance for the treatment of glioma. PMID- 26823705 TI - Evidence of a novel gene HERPUD1 in polypoidal choroidal vasculopathy. AB - Polypoidal choroidal vasculopathy (PCV) is an exudative maculopathy, with clinical features distinct from neovascular age-related macular degeneration (nAMD) which is the leading cause of irreversible blindness in the elderly. Our studies focused on the genetic background and function of a novel gene HERPUD1 in PCV. HERPUD1 has been reported to increase the level of amyloid beta (Abeta), which is a component of drusen deposits underlying the retinal pigment epithelium (RPE) layer. To verify the genetic functional associations of HERPUD1 with PCV, exome sequencing of HERPUD1 was performed in unrelated Chinese individuals, including nAMD patients, PCV patients and control subjects. Immunohistochemistry assays for HERPUD1 were performed in the subretinal membranes of PCV patients. The relationship between HERPUD1 and amyloid beta precursor was determined using real-time PCR in HERPUD1-overexpressing RPE cells. The gene expression patterns of angiogenesis cytokines and chemokines in both Abeta-treated RPE cells and in Brown Norway rats that received Abeta subretinal injections were determined. We showed that HERPUD1 rs2217332 is significant associated with Chinese PCV, and HERPUD1 was expressed in PCV subretinal membranes. Besides, Plasma Abeta42 protein was significantly higher in PCV patients compared to nAMD and control subjects. Abeta could upregulate angiogenic factors, chemokines and matrix metalloproteinases both in RPE cells and in a rat model of subretinal Abeta injection. The imbalance of the cytokines may be one of the mechanisms for the formation and development of PCV. Our results strongly suggest that HERPUD1 is highly associated with PCV patients. PMID- 26823707 TI - UCH-LI acts as a novel prognostic biomarker in gastric cardiac adenocarcinoma. AB - Gastric cardiac adenocarcinoma (GCA) accounts for a majority of gastric cancer population and harbors unfavorable outcome. Ubiquitin C-terminal hydrolase L1 (UCH-L1) belongs to the deubiquitinating enzyme family, which could regulate cell growth in human cancers. In the present study, expression of UCH-L1 was evaluated in 196 GCAs by immunohistochemistry using tissue microarray and its function on gastric cancer cells was measured. UCH-L1 expression was increased in GCA specimens, compared with their normal tissues and UCH-L1 overexpression is tightly correlated with tumor size and overall TNM stage. Log-rank analysis showed that UCH-L1 positive is reversely associated with cumulative survival (P<0.001). Multivariate Cox regression model showed that UCH-L1 overexpression is a remarkably negative predictor in GCA prognosis (Hazard Ratio=0.53, P<0.01), along with advanced TNM stage that is a known negative factor in gastric cancers (Hazard Ratio=0.33, P<0.05). Silencing of UCH-L1 reduced the ability of cell proliferation, colony formation, migration and invasion of gastric cancer cells. Our findings suggest that UCH-L1 is a promising prognostic biomarker for GCAs and might play an important role in the carcinogenesis of gastric cancer. PMID- 26823706 TI - Inflammation and cancer: inhibiting the progression of residual hepatic VX2 carcinoma by anti-inflammatory drug after incomplete radiofrequency ablation. AB - BACKGROUND: Accelerated progression of residual hepatocellular carcinoma (HCC) after incomplete radiofrequency ablation (RFA) has been reported more frequently. Recent data have redefined the concept of inflammation as a critical component of tumor progression. However, there has been little understanding regarding the relationship between progression of residual HCC and the inflammation induced by thermal destruction of the tumor after RFA. The present study was designed to determine whether inflammation facilitates rapid progression of residual hepatic VX2 carcinoma and to clarify the possible underlying mechanisms. METHODS: Forty eight rabbits were each implanted with two VX2 hepatic tumors via supraumbilical median laparotomy. One of the tumors in two different lobes was ablated by RFA. All the rabbits were then randomly divided into four groups (12 rabbits in each group) receiving anti-inflammatory treatment with different doses of aspirin: control group, AS-L group (aspirin, 5 mg/kg/d), AS-M group (aspirin, 20 mg/kg/d), and AS-H group (aspirin, 100 mg/kg/d). The levels of serum interleukin-6 (IL-6), high sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor-alpha (TNF-alpha) were detected to evaluate the effect of the anti-inflammation. Tumor growth, lung and kidney metastasis, and survival were assessed. The expression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), and cysteinyl aspartate specific proteinase 3 (caspase-3) in residual tumor was examined by immunohistochemistry and Western-blotting. RESULTS: The levels of serum IL-6, hs-CRP, and TNF-alpha in the AS-H group decreased significantly in comparison with those of the control group (P<0.05). The focal tumor volume and lung and kidney metastases of rabbits in the AS-H group were less significant compared with those of the control group (P<0.05). The expression of PCNA, MMP-9, and VEGF in the AS-H group decreased significantly compared with the control group (P<0.05). Finally, the survival time of the AS-H group was longer than that of the control group (P<0.05). CONCLUSIONS: Inflammation induced by thermal destruction of the tumor following RFA could be an important cause of rapid progression of residual hepatic VX2 carcinoma. The anti-inflammation effect of aspirin can inhibit proliferation, invasion, and metastasis of residual tumor cells, and aspirin may be a good candidate drug as an adjuvant therapy with RFA for treating HCC. PMID- 26823708 TI - Effects of portulacerebroside a on apoptosis of human leukemia HL60 cells and p38/JNK signaling pathway. AB - Acute myeloid leukemia is known as one of the most malignant diseases. We aimed at exploring the effect of portulacerebroside A (PCA) on the apoptosis in human leukemia HL60 cells and clarify the possible mechanisms involved in. By MTT analysis, we found that PCA (1-100 MUM) inhibited the cell viability in a time- and dose-dependent manner, and cell cycle was arrested at G0/G1 period. PCA treatment from 5 to 50 MUM dose-dependently induced apoptosis from 12.7 +/- 1.56% to 52.7 +/- 6.214% of HL60 cells. Mitochondrial membrane potential (MMP) was decreased and reactive oxygen species (ROS) accumulated obviously. mRNA expressions and protein levels of Bax/Bcl-2, caspase-3 and caspase-9 were elevated significantly. ERK1/2, JNK1/2 and p38 MAPK pathway were blocked detected by western blot analysis. In conclusion, PCA can act as a new agent for leucocythemia treatment. PMID- 26823709 TI - Relationship of Fas, FasL, p53 and bcl-2 expression in human non-small cell lung carcinomas. AB - OBJECTIVE: Lack of surface Fas expression is a main route for apoptotic resistance which is considered an important mechanism of tumorigenesis and tumor progression. Fas and FasL expression in 110 non-small cell lung carcinomas (NSCLCs) were investigated to evaluate their roles in pulmonary carcinogenesis and to examine the clinicopathologic significance of Fas expression with its relationship with p53 and bcl-2 over- expression. METHODS: Immunohistochemical analysis using tissue microarray demonstrated that a large proportion of NSCLC patients (60%) showed lack of membranous Fas expression. The Fas-negative cases revealed the significantly lower survival rate than Fas-positive ones. Also, the loss of Fas receptor expression was found more frequently in advanced stage and higher nodal status. FasL protein was increased in most NSCLCs (89%) compared to normal lungs. RESULTS: p53 and bcl-2 overexpression showed no association with Fas expression. Conclusively, reduced membranous Fas expression as a mechanism of apoptotic resistance is considered to play an important part of the pulmonary carcinogenesis, which may predict poor survival and have a negative prognostic influence. CONCLUSION: Increased FasL expression is thought to be a basis for the immune evasion in NSCLCs. The rare bcl-2 overexpression suggests that this anti apoptotic protein is unlikely to play a role in the apoptotic resistance of NSCLCs. PMID- 26823710 TI - B7-H3 in combination with regulatory T cell is associated with tumor progression in primary human non-small cell lung cancer. AB - B7-H3 belongs to the co-inhibitory B7 family and plays an important role in the adaptive immune response in regulating T cells. In human malignancies, B7-H3 is reported to be involved in tumor immune evasion. However, the detailed molecular mechanism of B7-H3 in tumor evasion remains unclear, particularly in non-small cell lung cancer (NSCLC). Regulatory T cells (Tregs) are known as a key player in the inhibition of immune mechanisms. The study demonstrated the correlation between B7-H3 on tumor cells and the number of Tregs in the tumor microenvironment in NSCLC. B7-H3 was examined in tumor tissues from 110 patients with NSCLC by immunohistochemical analysis. Forkhead box P3+ (FOXP3+) Tregs in those spencimens were also detected and numbered. Survival curves were drawn using the Kaplan-Meier method and compared by the log-rank test. High B7-H3 expression in tumor cells significantly correlated with male gender, squamous NSCLC, advanced stage and shorter overall survival (OS) (P = 0.035, P = 0.004, P = 0.037, P = 0.014, respectively). Meanwhile, FOXP3 expression in tumor infiltrating lymphocytes (TILs) was associated with male gender, regional lymph node involvement, advanced stage and worse OS (P = 0.009, P = 0.015, P = 0.014, P = 0.034, respectively). Significant correlation was identified between the expression of B7-H3 and the number of FOXP3+ TILs (P = 0.013). Patients with B7 H3 high/FOXP3 high had poorer OS (P = 0.006), suggesting that B7-H3 and Tregs may play a cooperatively role in tumor immune evasion, leading to poor outcomes for NSCLC patients. PMID- 26823712 TI - Knockdown of PFTK1 inhibits tumor cell proliferation, invasion and epithelial-to mesenchymal transition in pancreatic cancer. AB - PFTK1 was identified as a member of the cyclin-dependent kinase (CDK) family and it is frequently upregulated in many types of tumors. However, its expression and role in pancreatic cancer has not been yet reported. In this study, we aimed to explore the expression and function in pancreatic cancer. The present study verified that PFTK1 was highly expressed in pancreatic cancer cell lines. The in vitro experiments demonstrated that knockdown of PFTK1 inhibited the proliferation, migration and invasion of pancreatic cancer cells as well as the epithelial-to-mesenchymal transition (EMT) progress. Finally, knockdown of PFTK1 inhibited the expression of p-PI3K and p-Akt in pancreatic cancer cells. In summary, the present study has provided further evidence that knockdown of PFTK1 inhibited the proliferation and invasion of pancreatic cancer cells as well as the EMT progress by suppressing the PI3K/Akt signaling pathway. Therefore, these findings reveal that PFTK1 might potentially become a novel strategy for targeting pancreatic cancer. PMID- 26823711 TI - Increased synapsin I expression in cerebral malaria. AB - Synapsin I is a neuronal phosphoprotein contained in the synaptic vesicles of mammalian central and peripheral nervous systems. It regulates both neurotransmitter release and synaptic formation. Variations in synapsin I expression in the brain have been reported to cause brain malfunction. In severe malaria, neurological complications, such as convulsion, delirium and coma, suggest abnormalities in the release of neurotransmitters. This study evaluated synapsin I expression in cerebral malaria (CM). An immunohistochemical method was used to study the semi-quantitative and qualitative expression of synapsin I in the brain of CM patients (10 cases) who died with Plasmodium falciparum, compared with non-cerebral malaria (NCM) (4 cases), and control brain tissues (5). Synapsin I was expressed in the gray matter of the cerebral cortex and the molecular layer of the cerebellum, as a diffusely dense precipitate pattern in the neuropil, with no immunoreactivity in the neurons, neuronal dendrites, glial cells, endothelial cells, and Purkinje cells. The findings were similarly demonstrated in CM, NCM, and control brain tissues. However, in the granular layer of the cerebellum, a significant increase in synapsin I expression was observed in the granule cells, and the glomerular synaptic complex, from the CM group, compared with the NCM, and control brain tissues (all P < 0.05). Parasitemia showed a positive correlation with synapsin I expression in the granule cells (on admission: Spearman's rho = 0.600, P = 0.023) (before death: Spearman's rho = 0.678, P = 0.008), and glomerular synaptic complex (before death: Spearman's rho = 0.571, P = 0.033). It was hypothesized that CM causes pre synaptic excitation and eventually activation of synapsin I, leading to increased neurotransmitter release. Synapsin I inhibitor should be investigated further as a target for a therapeutic intervention to alleviate neurological symptoms in severe malaria. PMID- 26823713 TI - MiR-211 inhibits cell proliferation and invasion of gastric cancer by down regulating SOX4. AB - INTRODUCTION: Previous studies have shown that the dysregulation of miRNAs are frequently associated with cancer progression. Deregulation of miR-211 has been observed in various types of human cancers. However, its biological function in gastric cancer (GC) is still unknown. METHODS: The expression of miR-211 in GC was detected by using quantitative real-time PCR (qRT-PCR). The miR-211 mimics and inhibitor were designed and transfected into BGC-823 cells. Then, we explore the probable biological function of miR-211 in gastric cancer cell proliferation and invasion in vitro. A luciferase reporter assay and western blot were performed to confirm the target gene of miR-211. RESULTS: MiR-211 was significantly down-regulated in GC. Over-expression of miR-211 inhibited gastric cancer cell proliferation and invasion in vitro, conversely, down-regulated expression of miR-211 promoted gastric cancer cell proliferation and invasion. In addition, the sex-determining region Y-related high mobility group box 4 (SOX4) is identified as a target of miR-211 in GC cells, and SOX4 expression levels was inversely correlated with miR-211. Furthermore, knockdown of Sox4 inhibited the proliferation and invasion in GC cells. CONCLUSION: miR-211 could inhibit GC cell proliferation and invasion partially by down-regulating SOX4. MiR-211 might be a potential therapeutic target for GC treatment in the future. PMID- 26823714 TI - Baicalin protects against thrombin induced cell injury in SH-SY5Y cells. AB - Baicalin, an extract from the dried root of Scutellaria baicalensis Georgi, was shown to be neuroprotective. However, the precise mechanisms are incompletely known. In this study, we determined the effect of baicalin on thrombin induced cell injury in SH-SY5Y cells, and explored the possible mechanisms. SH-SY5Y cells was treated with thrombin alone or pre-treated with baicalin (5, 10, 20 MUM) for 2 h followed by thrombin treatment. Cells without thrombin and baicalin treatment were used as controls. Cell viability was detected by MTT assay. Cell apoptosis was analyzed by flow cytometry. Real-time PCR was performed to determine the mRNA expression of protease-activated receptor-1 (PAR-1). Western blotting was conducted to determine the protein expression of PAR-1, Caspase-3 and NF-kappaB. Baicalin reduced cell death following thrombin treatment in a dose-dependent manner, with concomitant inhibition of NF-kappaB activation and suppression of PAR-1 expression. In addition, baicalin reduced Caspase-3 expression. The above findings indicated that baicalin prevents against cell injury after thrombin stimulation possibly through inhibition of PAR-1 expression and NF-kappaB activation. PMID- 26823715 TI - Modulatory role of garlicin in migration and invasion of intrahepatic cholangiocarcinoma via PI3K/AKT pathway. AB - Increasing evidences have indicated the role of garlicin in inhibiting the progression of various tumors including glioma, pulmonary carcinoma and pancreatic carcinoma, via mediating cell apoptosis or cell cycle. The regulatory effect and related molecular mechanism of garlicin in intrahepatic cholangiocarcinoma, however, remained unknown. This study thus aimed to investigate this scientific issue. HCCC-9810 cell line was treated with serially diluted garlicin, followed by cell proliferation assay using MTT approach. Transwell migration and invasion assays were further employed the regulatory effect of garlicin. The expression level of p-AKT and AKT proteins in tumor cells was quantified by Western blot. The growth of tumor cells was significantly inhibited by high concentration of garlicin (> 1.5 MUM). Lower concentration of garlicin showed dose-dependent inhibition of tumor cell invasion and migration. After using specific agonist IGF-1 (50 ng/mL) of PI3K/AKT signaling pathway, such facilitating effects of garlicin were depressed (P < 0.05). Western blotting showed significantly decreased phosphorylation level of AKT after treated with gradient concentrations of garlicin, while leaving the total AKT protein level unchanged. Garlicin may inhibit the invasion and migration of intrahepatic cholangiocarcinoma cells via inhibiting PI3K/AKT signaling pathway. PMID- 26823716 TI - Expression of livin, survivin and caspase-3 in prostatic cancer and their clinical significance. AB - To explore the expressions level of Livin, Survivin and Caspase-3 in prostatic cancer and the relationship among the 3 proteins and the clinicopathological features as well as the correlation among them. Totally, 43 paraffin-embedded prostate cancer tissues obtained from patients who were performed with rectal prostate biopsy or excision and 17 paraffin-embedded prostatic hyperplasia tissues were collected. All the specimens were confirmed by pathology. Immunohistochemistry SP method was used to detect the expressions of Livin, Survivin and Caspase-3 in prostatic cancer compared to hyperplasia tissues. The positive expression rates of both Livin and Survivin in prostatic cancer tissue were higher than those in prostatic hyperplasia tissue (93.02% vs. 64.70%, P < 0.05; 83.72% vs. 35.29%, P < 0.01). However, the positive expression rate of Caspase-3 in prostatic cancer tissue was obviously lower than that in prostatic hyperplasia tissue (25.58% vs. 58.82%, P < 0.01). Both Livin and Survivin expressions in prostatic cancer tissue were related to pathological grading (Gleason scores) (X(2) = 14.000, P = 0.001), but not related to preoperative PSA, clinical stages and distant metastasis (P > 0.05). Capsase-3 expression in prostatic cancer tissue was related to pathological grading (Gleason scores) (X (2) = 14.000, P = 0.001) and clinical stages (X (2) = 4.896, P = 0.027), but not related to preoperative PSA and distant metastasis (P > 0.05). In prostatic cancer tissue, Livin expression had no correlation with Survivin expression (r = 0.127, P = 0.419 > 0.05), but negatively correlated with Caspase-3 expression (r = -0.497, P = 0.001). Survivin expression was negatively correlated with Caspase 3 expression (r = -0.354, P = 0.020). Livin, Survivin and Caspase-3 are closely related to the occurrence and development of prostatic cancer and which are expected to become new targets for diagnosis and treatment in future. PMID- 26823717 TI - Primary splenic angiosarcoma with fever and anemia: a case report and literature review. AB - Primary splenic angiosarcoma is an extremely rare and aggressive neoplasm. The prognosis of this disease is dismal, and the mean survival is less than 6 months after the diagnosis. This neoplasm typically presents with abdominal pain, splenomegaly, weight loss, and spontaneous splenic rupture. Fever is a very rare presentation of splenic angiosarcoma. Here we report the case of a 64-year-old man who presented with fever and anemia. A laparoscopic splenectomy was performed and revealed splenic angiosarcoma. The postoperative course was uneventful and the patient received 5 cycles of adjuvant chemotherapy with ifosfamide plus epirubicin. He remained disease free at 9 months after surgery. This is the first case of splenic angiosarcoma with fever as the initial presentation that was treated with laparoscopic splenectomy to be reported in the English literature. PMID- 26823718 TI - Pigmented villonodular synovitis of the elbow with rdial, median and ulnar nerve compression. AB - Pigmented villonodular synovitis (PVNS) is a rare, idiopathic proliferative disorder of the synovium. While, PVNS of elbow is extremely rare. We report an 82 year-old female patient with 20-year-history of gradually increased PVNS in her left elbow. The multiple masses were located in anterior, medial and lateral of elbow. Her radial, median and ulnar nerves were compressed by the tumor. We resected tumor of extra-articular part piecemeally and released the compression of nerves. After the surgery, the patient gained a functional recovery. Two years after surgery she had a tumor recurrence, but without any symptoms of nerve compression syndromes. We discussed its clinical diagnosis, radiological features, MRI findings, pathophysiology, and treatment. PMID- 26823719 TI - MicroRNA-155 induces differentiation of RAW264.7 cells into dendritic-like cells. AB - MicroRNA (miRNA, miR)-155 is the most promising pro-inflammatory miRNA molecule. Lipopolysaccharide (LPS) and oxidized low-density lipoprotein (oxLDL) are the most well-known foreign antigens, initiating immune responses against infection and the development of atherosclerosis (AS), respectively. To explore whether miR 155 is involved in regulating LPS- and oxLDL-initiated inflammations, we investigated the level of miR-155 in both LPS- and oxLDL-treated RAW264.7 cells, assessed whether miR-155 induce morphologic changes of the cells and how did it regulate the production of surface markers and cytokines. The results showed that the level of miR-155 was significantly increased by LPS and was modestly increased by oxLDL. Moreover, RAW264.7 cells displayed morphological transformations from macrophage-like cells into DC-like cells when miR-155 was over-expressed. Furthermore, the gain- and loss-of-function studies demonstrated that miR-155 induced the expression of the surface markers (including MHC-II, MHC I, CD86, and CD83) and pro-inflammatory cytokines (including interleukin (IL)-12, IL-6, and IL-1b) in both LPS- and oxLDL-treated RAW264.7 cells. Additionally, miR 155 induced the expression of CD36 in oxLDL-treated RAW264.7 cells. In conclusion, up-regulated miR-155 is able to induce morphological and phenotypic changes, and the expression of pro-inflammatory cytokines in both LPS- and oxLDL treated RAW264.7 cells. Therefore, our study suggests that miR-155 is one important regulator involved in enhancing both LPS- and oxLDL-initiated inflammations, which is critical for the progression of immune responses as well as for the development of AS. PMID- 26823720 TI - FK506 ameliorates podocyte injury in type 2 diabetic nephropathy by down regulating TRPC6 and NFAT expression. AB - Diabetic nephropathy (DN) is the leading cause of end-stage renal failure, and podocyte injury plays a major role in the development of DN. In this study, we investigated whether tacrolimus (FK506), an immunosuppressor, can attenuate podocyte injury in a type 2 diabetic mellitus (T2DM) rat model with DN. Transmission electron microcopy was used to morphologically evaluate renal injury. The urinary albumin (UAL), creatinine clearance rate (Ccr) and major biochemical parameters, including glucose, insulin, serum creatinine (Scr), urea nitrogen, total cholesterol (CHO) and triglyceride (TG), were examined 12 weeks after the administration of FK506. The expressions of the canonical transient receptor potential 6 (TRPC6), nuclear factor of activated T-cells (NFAT) and nephrin were detected by Western blotting and qPCR. In the rat model of DN, the expressions of TRPC6 and NFAT were significantly elevated compared with the normal rat group; however, the treatment with FK506 normalized the increased expression of TRPC6 and NFAT and attenuated podocyte ultrastructure injury. UAL, Ccr and the biochemical parameters were also improved by the use of FK506. In cell experiments, FK506 improved the decreased expression of nephrin and suppressed the elevated expression of both TRPC6 and NFAT caused by high glucose in accordance with TRPC6 blocker U73122. Our results demonstrated that FK506 could ameliorate podocyte injury in T2DM, which may be related to suppressed expressions of TRPC6 and NFAT. PMID- 26823721 TI - Procoagulant role of neutrophil extracellular traps in patients with gastric cancer. AB - BACKGROUND: Patients with gastric cancer (GC) commonly exhibit a hypercoagulable state that results in significant morbidity and mortality. Recent studies have shown that neutrophil extracellular traps (NETs) trigger coagulation through an intrinsic pathway and contribute to thrombus initiation and progression. In this study, we aimed to determine the procoagulant activity (PCA) of NETs in patients with GC. METHODS: NET formation and their PCAs were assessed in 48 patients with GC and 36 healthy controls using immunofluorescence microscopy of neutrophil markers and extracellular DNA as well as a modified capture ELISA technique, and thrombin-antithrombin complex and clot (fibrin) spectroscopic detection, respectively. RESULTS: Here we showed that neutrophils isolated from patients with GC displayed significantly enhanced NET formation compared with those from healthy controls; furthermore, plasma or platelets obtained from patients with GC induced control neutrophils to release NETs. In addition, NETs released by GC neutrophils significantly increased the potency of control plasma to generate thrombin and fibrin. Notably, these procoagulant effects were dramatically attenuated by application of DNase I. We further found that spontaneous NET formation in patients with GC was significantly higher than that in controls, increased with tumor- node-metastasis stage elevation, and positively correlated with thrombin-antithrombin complex levels and D-dimers. Additionally, the effect of DNase I on cell-free plasma generation of fibrin was dependent on the concentration of NET formation. CONCLUSION: These results suggest that GC creates a systemic environment that primes neutrophils to release procoagulant NETs. Thus, targeting NETs might improve the coagulopathy of patients with GC. PMID- 26823722 TI - Differences in gene expression profiles and signaling pathways in rhabdomyolysis induced acute kidney injury. AB - PURPOSE: Rhabdomyolysis is a threatening syndrome because it causes the breakdown of skeletal muscle. Muscle destruction leads to the release of myoglobin, intracellular proteins, and electrolytes into the circulation. The aim of this study was to investigate the differences in gene expression profiles and signaling pathways upon rhabdomyolysis-induced acute kidney injury (AKI). METHODS: In this study, we used glycerol-induced renal injury as a model of rhabdomyolysis-induced AKI. We analyzed data and relevant information from the Gene Expression Omnibus database (No: GSE44925). The gene expression data for three untreated mice were compared to data for five mice with rhabdomyolysis induced AKI. The expression profiling of the three untreated mice and the five rhabdomyolysis-induced AKI mice was performed using microarray analysis. We examined the levels of Cyp3a13, Rela, Aldh7a1, Jun, CD14. And Cdkn1a using RT-PCR to determine the accuracy of the microarray results. RESULTS: The microarray analysis showed that there were 1050 downregulated and 659 upregulated genes in the rhabdomyolysis-induced AKI mice compared to the control group. The interactions of all differentially expressed genes in the Signal-Net were analyzed. Cyp3a13 and Rela had the most interactions with other genes. The data showed that Rela and Aldh7a1 were the key nodes and had important positions in the Signal-Net. The genes Jun, CD14, and Cdkn1a were also significantly upregulated. The pathway analysis classified the differentially expressed genes into 71 downregulated and 48 upregulated pathways including the PI3K/Akt, MAPK, and NF-kappaB signaling pathways. CONCLUSION: The results of this study indicate that the NF-kappaB, MAPK, PI3K/Akt, and apoptotic pathways are regulated in rhabdomyolysis-induced AKI. PMID- 26823723 TI - Gastrodin improves cognitive dysfunction and decreases oxidative stress in vascular dementia rats induced by chronic ischemia. AB - OBJECTIVE: To study the potential protective effects of gastrodin on reducing tissue oxidative stress and attenuating cognitive deficits in vascular dementia induced by cerebral chronic hyperfusion. To explore the detailed molecular mechanisms. METHODS: 6 to 8 week old male Wistar rats were adopted as experimental animals. Animals were divided into the following groups: Group 1 (sham group with no occlusion), Group 2 (control group with 2VO procedure), Group 3 (sham group with gastrodin administration), Group 4 (2VO group with gastrodin administration). Morris water maze (MWM) test was adopted to test the learning and memory function of rats within different groups. MDA, glutathione peroxidase and total thiol assessment was done to reflect the oxidative stress in the brain tissue. Cell counting kit-8 (CCK8) and flow cytometry (FCM) were performed to examine the cell viability and apoptosis rate of SH-SY5Y cells induced by hydrogen peroxide and rescued by gastrodin treatments. Reactive oxygen species (ROS) generation was determined by the 2', 7'-dichlorofluorescein diacetate (DCFH DA) assay. qPCR and Western blot (WB) were adopted to detect the molecular mechanisms related to the anti-apoptosis and ROS scavenging effects of gastrodin. RESULTS: Our results indicated an obvious protective effect of gastrodin on vascular dementia induced brain ischemia. Administration of gastrodin could improve the impaired learning and memory function induced by 2VO procedure in rats. The levels of MDA were partially decreased by the administration of gastrodin. The levels of glutathione peroxidase and total thiol were partially restored by the administration of gastrodin. Cell viability was improved by gastrodin in a dose-dependent pattern on SH-SY5Y cells induced by hydrogen peroxide (P < 0.05). Cell apoptosis rate was reduced by gastrodin in a dose dependent pattern on SH-SY5Y cells induced by hydrogen peroxide (P < 0.05). Gastrodin could scavenge ROS generation induced by pre-treatment of hydrogen peroxide. Both qPCR and WB results showed significant enhancements on the expression levels of NFE2L2, ADH7, GPX2 and GPX3 (P < 0.05). CONCLUSION: Gastrodin administration is protective on the learning and memory functions that might be affected by vascular dementia induced oxidative stress due to brain ischemia. On the molecular level, NFE2L2, ADH7, GPX2 and GPX3 were up regulated by gastrodin. PMID- 26823724 TI - MiR-195 is a key negative regulator of hepatocellular carcinoma metastasis by targeting FGF2 and VEGFA. AB - Hepatocellular carcinoma (HCC) is the most common primary tumor of liver and the fifth most common cancer in the world. Lung is the most frequent site for extra hepatic metastasis from hepatocellular carcinoma, while the cause and mechanism of it is still poor understood. Here, we identify that the expression of miR-195 is markedly impaired in the lung metastasis cell lines of HCC. The result of Real time PCR reveals the expression of miR-195 is significantly downregulated in 92 HCC tissues. Low expression of miR-195 is associated with tumor size, portal vein thrombosis, TNM stage and patients survival. Luciferase reporter and ELISA assay prove that hematogenous metastasis related genes including FGF2 and VEGFA are the target genes of miR-195. Overexpression of miR-195 in HCC cell line BEL-7402 markedly inhibits the capability of migration and invasion. Taken together, our results suggest that miR-195, a tumor suppressor miRNA, contributes to the lung metastasis of HCC by negatively regulating FGF2 and VEGFA, providing key implications of miR-195 for the therapeutic intervention of HCC. PMID- 26823725 TI - Osteopontin facilitates invasion in human trophoblastic cells via promoting matrix metalloproteinase-9 in vitro. AB - Successful implantation of embryo and placentation depend on proper trophoblast proliferation and differentiated into specialized invasive trophoblast. However, little is known about the regulatory factors and mechanisms in trophoblast proliferation and differentiation. Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. It has been identified that OPN is highly expressed in invasive trophoblasts in human placenta. In this study, we demonstrated that OPN is constitutively expressed in highly invasive phenotype of human choriocarcinoma cell lines of JAR and JEG-3 cells, and OPN could promote trophoblast proliferation and invasion, partly through promoting MMP-9 secretion. Inhibition of OPN will compromise the abilities of proliferation and invasion in JAR and JEG 3 cell lines. Our data showed that the expression of OPN in trophoblast may participate in placentation, OPN expression defects may be involved in gestational trophoblastic diseases. PMID- 26823726 TI - Combined identification of long non-coding RNA CCAT1 and HOTAIR in serum as an effective screening for colorectal carcinoma. AB - Long non-coding RNAs (lncRNAs) CCAT1 and HOTAIR have been shown to play an important regulatory role in cancer biology, and CCAT1 and HOTAIR are upregulated in several cancers, however, its value in the diagnosis of colorectal cancer (CRC) is unclear. Therefore, the aim of this study is to evaluate the clinical significance of plasma CCAT1 and HOTAIR as a biomarker in the screening of CRC. In our study, we found that the levels of HOTAIR (P < 0.05) and CCAT1 (P < 0.05) were significantly higher in plasma of CRC patients than that of the healthy control. Moreover, the levels of lincRNA-p21 (P < 0.05) were obviously decreased in plasma of CRC patients as compared to those of healthy control. There was highly correlated for CCAT1 (R = 0.752, mean differences = -0.06 +/- 1.20), HOTAIR (R = 0.739, mean differences = -0.26 +/- 0.76) and lincRNA-p21 (R = 0.848, mean differences = -0.41 +/- 0.89) in plasma and serum. By receiver operating characteristic curve (ROC) analysis, plasma CCAT1 provided the higher diagnostic performance for detection of CRC (the area under the ROC curve (AUC), 0.836; P < 0.001; sensitivity, 75.7%; specificity, 85.3%). Moreover, CCAT1 combining with HOTAIR could provide a more effective diagnosis performance (AUC, 0.954, P < 0.001, sensitivity, 84.3%; specificity, 80.2%). Most importantly, this combination was effective to detect CRC at an early stage (85%). In conclusion, our results demonstrated that increased plasma HOTAIR and CCAT1 could be used as a predictive biomarker for CRC screening, and that combination of HOTAIR and CCAT1 had a higher positive diagnostic rate of CRC than HOTAIR or CCAT1 alone. PMID- 26823727 TI - Assessing the efficacy and safety of combined DPP-4 inhibitor and insulin treatment in patients with type 2 diabetes: a meta-analysis. AB - The use of DPP-4 inhibitors in combination with insulin has been proposed as an alternative therapeutic option for poorly controlled type 2 diabetes (T2D) patients. We thus performed a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and safety of this combination therapy in adult T2D patients. Seven eligible studies involving 3,384 participants were included for the study. The resulting data revealed that the combination therapy of DPP-4 inhibitor and insulin is associated with a modest reduction in HbA1c (-0.52%; 95% CI -0.59 to -0.44), a decrease in 2h-PPG (-1.81 mmol/l; -2.23 to -1.38), and an increase in the proportion of patients reaching the target HbA1c of <= 7% (RR 2.24; 95% CI 1.80 to 2.77) without increasing the risk of hypoglycemia (RR 1.04; 0.83 to 1.31) or body weight (-0.11 kg; -0.56 to 0.33), as compared with other anti-diabetic treatments. These results support that this combination therapy could serve as a potential therapeutic strategy that offers an alternative option for patients inadequately controlled on other anti-diabetic agents in clinical practice. PMID- 26823728 TI - Proteomic analysis of mitral valve in Lewis rat with acute rheumatic heart disease. AB - Rheumatic heart disease (RHD) makes a heavy burden in human lives and economy. The proteomic analysis of acute rheumatic heart disease (ARHD) can provide precious data to study RHD at the early stages, but no one has looked into. So based on our early research we applied the method of continuous GAS stimulation on Lewis rats to duplicate the animal model of ARHD. And the mitral valves of rats in control group (n=10) and ARHD group (n=10) were selected for proteomic analysis of ARHD with the iTRAQ labeling based 2D LC-ESI-MS/MS quantitative technology. We identified 3931 proteins in valve tissue out of which we obtained 395 differentially expressed proteins containing 176 up-regulated proteins and 119 down-regulated proteins. Changes in levels of GAPDH (6.793 times higher than the control group) and CD9 (2.63 times higher than the control group) were confirmed by Western blot or immunohistochemistry. The differentially expressed proteins such as GAPDH, CD9, myosin, collagen and RAC1 may be potential biomarkers for ARHD. Moreover, the mitral valve protein profile shed light on further understanding and investigating ARHD. PMID- 26823729 TI - Expression and functional role of miR-29b in renal cell carcinoma. AB - OBJECTIVES: microRNAs (miRNAs) play essential roles in many tumors, including renal cell carcinoma (RCC). The aim of the present study was to investigate the expression and functional role of miR-29b in RCC and to identify its target genes. METHODS: We determined the expression of miR-29b in clear cell RCC (ccRCC) tissues and RCC cell lines (786-O, A498, and SN12-PM6) using quantitative real time PCR (qRT-PCR). The associations between miR-29b expression and clinical pathological parameters and prognosis were explored. Besides, the role of miR-29b in the SN12-PM6 cells proliferation, apoptosis, cycle, and invasion were investigated after transduction with lentivirus vectors. The kines in family member 1B (KIF1B), possible miR-29b target genes, were predicted using bioinformatics approaches, as well as the role in the pathogenesis of RCC. RESULTS: Elevated expression of miR-29b was found in both tumor tissues and cell lines. High expression of miR-29b was significantly associated with tumor-node metastasis (TNM) stage (P = 0.026) and the overall survival (P = 0.009) in the ccRCC. Inhibition of miR-29b expression could promote apoptosis, and inhibit proliferation and invasion ability in SN12-PM6 cells. Also, we confirmed that miR 29b could directly regulate the expression of KIF1B at the post transcriptional level. CONCLUSION: These data suggest that miR-29b acts as an oncomiR, promoting proliferation and invasion ability through KIF1B suppression, and it might be a potential marker for prognosis of RCC. PMID- 26823730 TI - KyoT2 downregulates airway remodeling in asthma. AB - The typical pathological features of asthma are airway remodeling and airway hyperresponsiveness (AHR). KyoT2, a negative modulator of Notch signaling, has been linked to asthma in several previous studies. However, whether KyoT2 is involved in the regulation of airway remodeling or the modulation of airway resistance in asthma is unclear. In this study, we aimed to evaluate the therapeutic potential of KyoT2 in preventing asthma-associated airway remodeling and AHR. BALB/c mice were used to generate a mouse model of asthma. Additionally, the expression of Hes1 and Notch1 in airway was analyzed using Immunofluorescence examination. The asthmatic mice were intranasally administered adenovirus expressing KyoT2 and were compared to control groups. Furthermore, subepithelial fibrosis and other airway remodeling features were analyzed using hematoxylin and eosin staining, Van Gieson's staining and Masson's trichrome staining. AHR was also evaluated. This study revealed that KyoT2 downregulated the expression of Hes1, repressed airway remodeling, and alleviated AHR in asthmatic mice. It is reasonable to assume that KyoT2 downregulates airway remodeling and resistance in asthmatic mice through a Hes1-dependent mechanism. Therefore, KyoT2 is a potential clinical treatment strategy for asthma. PMID- 26823731 TI - Expression of minichromosome maintenance 8 in chronic myelogenous leukemia. AB - OBJECTIVES: Minichromosome maintenance 8 (MCM8) is identified as an initiating helicase involved in DNA elongation and involved in cancer. However, little information is available for the role of MCM8 on chronic myelogenous leukemia (CML). We aimed to explore the expression and effect of MCM8 on CML. METHODS: Peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) were prepared from six patients with CML and three healthy individuals. The mRNA levels of MCM8 were determined and compared. The expression of MCM8 was silenced by small interfering RNA (siRNA) approach in human CML cell line K562. After transfection with MCM8 siRNA, cell viability and apoptotic rate were analyzed, as well as the protein expression levels of Caspase-3 and B-cell lymphoma (Bcl)-xL. RESULTS: Relative mRNA levels of MCM8 were both significantly higher in PBMC and BMMC from CML patients than those in healthy individuals (P < 0.05). The cell viability was significantly reduced while the apoptotic rate was statistically increased by knockdown of MCM8 compared to control group or the scramble siRNA group (both P < 0.05). Moreover, the protein expression levels of Caspase-3 were significantly increased (P < 0.05), and while the levels of Bcl-xL were statistically reduced (P < 0.05) compared to the control group or the scramble siRNA group. CONCLUSION: MCM8 plays a significant role in CML, and knockdown of MCM8 might be a potentially targeted therapy for CML. PMID- 26823732 TI - Epistaxis and pituitary apoplexy due to ruptured internal carotid artery aneurysm embedded within pituitary adenoma. AB - Epistaxis due to ruptured internal carotid artery (ICA) aneurysm embedded within a pituitary adenoma (PA) has seldom been reported in the literature. Here we want to elaborate the incidence, mechanisms, clinical manifestations, and treatment strategy for this condition. The first survived case of a patient with epistaxis and pituitary apoplexy due to ruptured aneurysm embedded within PA was reported and the literature was reviewed. A 53-year-old male patient presented to our institution with sudden onset epistaxis and progressive vision loss. Neurological examination revealed bilateral ptosis and dilated unresponsive pupils. A CT scan showed a large mass in the pituitary fossa with bony erosion. MRI revealed a large pituitary tumor and abnormal signal intensity in the tumor. No aneurysm was noted during the pre-operative MR angiography. Abundant arterial bleeding suddenly occurred during urgent transsphenoidal surgery. Digital subtraction angiography confirmed the presence of a 14 mm unexpected saccular aneurysm of right ICA in the cavernous sinus with the dome protruding into the sella turcica. Balloon test occlusion of the right ICA was undertaken and permanent occlusion was performed. The patient recovered well and received bromocriptine and thyroid hormone replacement therapy during the follow-up period. At 14-month followup, the patient had no neurological deficits, no features of ischaemia relating to the right ICA therapeutic occlusion. Our case indicated that epistaxis and pituitary apoplexy could be due to the rupture of an ICA aneurysm embedded in a PA. Clinical suspicion should remain high when evaluating any case of epistaxis and pituitary apoplexy. Optimal treatment should take into consideration individual features of the tumor, aneurysm, and patient. Making the correct diagnosis as well as identifying an appropriate management strategy is critical in the care of such patients. PMID- 26823733 TI - Low long non-coding RNA HOTAIR expression is associated with down-regulation of Nrf2 in the spermatozoa of patients with asthenozoospermia or oligoasthenozoospermia. AB - HOTAIR, a long noncoding RNA, regulates development and progression of tumor cells and function of normal stem cells. However, the role and the molecular mechanism of HOTAIR in the spermatozoa of patients with asthenozoospermia and oligoasthenozoospermia are still unclear. Herein, 45 healthy control, 45 asthenozoospermic patients and 45 oligoasthenozoospermic patients were enrolled. Initially, through analyzing HOTAIR expression, we observed a decreased level of HOTAIR expression in patients. Subsequently, we found that there was a positive correlation between HOTAIR expression and Nrf2 expression in patients. The low expression of HOTAIR was also observed to be associated with specific sperm function parameters, including motility and vitality. In the ejaculated spermatozoa from patients, low level of histone H4 acetylation of the Nrf2 gene promoter was observed. Finally, we found that downregulation of HOTAIR expression reduced histone H4 acetylation in Nrf2 promoter and Nrf2 expression. Therefore, this study demonstrated that HOTAIR expression was low in the spermatozoa of patients with asthenozoospermia and oligoasthenozoospermia, which resulted in down-regulation of Nrf2 expression. Our data suggested the decrease of HOTAIR expression led to ROS related defects in sperm function. PMID- 26823734 TI - Use of aquaporins 1 and 5 levels as a diagnostic marker in mild-to-moderate adult onset asthma. AB - Characteristic features of asthma include airway inflammation and hyperactivity, mucus hypersecretion, mucosal edema, and airway remodeling. These features could be due to pathological water transport across pulmonary epithelia and aquaporins (AQPs) have recently been isolated as key proteins in fluid transportation in the human respiratory tract. We aimed to evaluate the role of aquaporins in the pathogenesis of asthma and their possible use a diagnostic marker of the disease. A total of 110 hospitalized and outpatients with mild to moderate adult-onset asthma were invited to participate in this study and 34 submitted an induced sputum sample adequate for analysis. The amount of AQP1, AQP5 and MUC5AC were measured with ELISA assay. The amount of IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN gamma and IL-17 in both serum and sputum were measured with Cytometry Bead Array (CBA kit). Our results suggest that sputum AQP5, AQP1 and MUC5AC are all in a good correlation (r=0.498 between AQP5 and AQP1, r=0.529 and r=0.661 between MUC5AC and AQP5 or AQP1, respectively, all P<0.05). The AUC value for AQP1 and AQP5 to diagnose asthma were 0.729 and 0.745, respectively. In conclusion, water homeostasis plays an important role in maintaining adequate fluid transportation within the lung and is involved in the pathogenesis of asthma. Our results suggest that AQP may influence pulmonary physiology that their dysfunction can contribute to pulmonary pathogenesis, such as asthma. Moreover, their quantification could serve as biomarkers for the diagnosis of asthma. PMID- 26823735 TI - Raf kinase inhibitor protein (RKIP) inhibits the cell migration and invasion in human glioma cell lines in vitro. AB - OBJECTIVE: To investigate the effects and the potential mechanisms of RKIP on cell migration, invasion and proliferation in human glioma cell lines in vitro. METHODS: The RKIP over-expressing and RKIP knockdown human U87 glioma cells were used to reveal the effects of RKIP on human glioma cells migration, invasion and proliferation. After the recombinant plasmid pcDNA3.0-RKIP or RKIP-shRNA was transfected into the cell lines U87 by the means of liposome assay, the cells migration, invasion and proliferation were detected by wound healing, Transwell and MTT assay. Then, the levels of RKIP, MMP-3, MMP-9 and HMGA2 mRNA transcription were measured by means of RT-qPCR and levels of proteins expressions were determined using Western blot. RESULTS: The results of MTT assay suggested that the PKIP have little inhibitive effects on glioma cells proliferation (P>0.05). The present paper showed that the migration distances in the group of RKIP-shRNA were markedly increased compared to the pcDNA3.0-RKIP and control. Similarly, the results showed that the numbers of invasion cells in RKIP shRNA were remarkably increased than the pcDNA3.0-RKIP group and control group. Western blot and RT-qPCR suggested that over-expressions of RKIP lessened the MMP 2, MMP-9 and HMGA2 expression, however, turning down the RKIP expression showed the inverse effects. CONCLUSION: RKIP inhibits the cells migrations and invasions. Meanwhile, RKIP might inhibit the glioma cells through inhibiting MMPs and HMAG2 expression. Therefore, we demonstrated that RKIP is an underlying target for the treatment of glioma. PMID- 26823736 TI - Down-regulation of microRNA-184 contributes to the development of cyanotic congenital heart diseases. AB - PURPOSE: We aimed to investigate the roles of miR-184 in adaptation of hypoxic cardiomyocytes, as well as to elucidate the possible mechanisms of miR-184 in the development of cyanotic congenital heart diseases (CHD). MATERIALS AND METHODS: We conducted quantitative real-time polymerase chain reaction (qRT-PCR) to determine the expression of miR-184 in patients with cyanotic cardiac defects. The embryonic rat ventricular myocardial H9c2 cells were transfected with miR-184 inhibitor and negative scramble RNA. Mock group was untreated by anything. We then used MTT assay and in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) to determine whether inhibition of miR-184 in vitro affect cell proliferation and apoptosis under hypoxic conditions. Besides, the expression levels of caspase-3 and caspase-9 in hypoxic H9c2 cells were determined by western blot. RESULTS: MiR-184 was significantly down-regulated in CHD patients with cyanotic cardiac defects. In addition, miR-184 was successfully inhibited in hypoxic H9c2 cells. Moreover, inhibition of miR-184 markedly decreased cell viability and obviously induced apoptosis under hypoxic conditions in vitro. Besides, the expression levels of caspase-3 and caspase-9 in hypoxic H9c2 were significantly increased after miR-184 inhibition. CONCLUSIONS: Our findings indicate that inhibition of microRNA-184 may contribute to the development of cyanotic CHD via decreasing proliferation and inducing apoptosis of cardiomyocytes. Moreover, miR-184 inhibition may promote hypoxia-induced apoptosis via activation of caspase-3 and caspase-9. Congenital down-regulation of miR-184 may be a mechanism leading to CHD development. PMID- 26823737 TI - Methylation status of TRAF2 is associated with the diagnosis and prognosis of gastric cancer. AB - The purpose was to investigate whether the expression level of TRAF2 gene was regulated by DNA methylation and explore the role of TRAF2 methylation in the diagnosis and prognosis of gastric cancer (GC). Firstly, we detected the expression of TRAF2 both at mRNA level and protein level. And the up-regulated of TRAF2 expression at two different levels were both found (P<0.001). Then we measured the methylated status of TRAF2 by MSP and got a result of that TRAF2 was hypomethylated in GC patients compared with healthy controls (P<0.001). Meanwhile, the relationship between TRAF2 methylation and clinicopathologic characteristics was estimated through chi-square. The outcome proved that TRAF2 methylation was impacted by age (P=0.024), lymph node metastasis (P=0.046), TNM stage (P=0.021), distant metastasis (P=0.002) and depth of invasion (P=0.002). The AUC of 0.795 accompanying a sensitivity of 66.7% and a specificity of 94.7% were obtained from Receiver Operating Characteristic (ROC) curve which indicated the diagnostic value of TRAF2 methylation was high. At last, we researched the prognostic value of TRAF2 methylation. Kaplan-Meier showed that patients with TRAF2 hypomethylation had lived much shorter than those with TRAF2 hypermethylation (log rank test, P<0.001). Cox regression analysis revealed TRAF2 hypomethylation (HR=18.827, 95% CI=3.103-114.222, P=0.001), lymph node metastasis (HR=0.154, 95% CI=0.047-0.512, P=0.002), distant metastasis (HR=3.032, 95% CI=1.116-8.237, P=0.030), as well as differentiation (HR=0.287, 95% CI=0.113 0.731, P=0.009) were all vital prognostic factors in GC. Taken together, TRAF2 expression was increased in GC patients by DNA hypomethylation and this methylation could be an independent diagnostic and prognostic indicator in GC. PMID- 26823738 TI - MiR-152 regulates metastases of non-small cell lung cancer cells by targeting neuropilin-1. AB - MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been suggested to play critical roles in tumorigenesis. Recently, miR-152 was reported to be dysregulated in some human cancers. However, the function and mechanism of miR 152 in non-small cell lung cancer (NSCLC) is still unclear. In the present study, our findings showed that the expression of miR-152 was significantly down regulated and neuropilin-1 was up-regulated in the NSCLC specimens. Moreover, the levels of miR-152 and neuropilin-1 were inversely correlated. Bioinformatics analyses and luciferase reporter assay showed that miR-152 targeted the 3'-UTR of neuropilin-1 mRNA to inhibit its translation. Furthermore, overexpression of miR 152 inhibited neuropilin-1 mediated cell invasiveness, while down-regulated expression of miR-152 increased neuropilin-1 mediated cell invasiveness in NSCLC cells. Together, these findings indicated that miR-152 suppression in NSCLC cells might promote neuropilin-1 mediated cancer metastasis and suggested a new therapeutic application of miR-152 in the treatment of NSCLC. PMID- 26823739 TI - Effect of miR-143 on the apoptosis of osteosarcoma cells. AB - As one common malignant bone cancer, osteosarcoma is mainly occurred in young people with increasing incidences. Current treatment of osteosarcoma includes surgery and chemo-/radio-therapy. Due to the unclear pathogenesis mechanism, the overall treatment efficacy is still not satisfactory. As anti-apoptotic molecule Bcl-2 has been suggested to be related with osteosarcoma and is regulated by miR 143, we thus investigated the correlation between miR-143 and Bcl-2 in osteosarcoma patients, in an attempt to elucidate the role of miR-143 in cancer occurrence. Real-time fluorescent RT-PCR was used to quantify expression levels of miR-143 and Bcl-2 from a total of 5 osteosarcoma patients, along with protein contents determination by Western blotting. In vitro study was also performed to detect Bcl-2 expression and cell apoptosis via silencing or over-expressing miR 143 in cultured osteosarcoma cells. MiR-143 showed down-regulation in osteosarcoma tissues. Bcl-2, however, had elevated expression in cancer cells when compared to adjacent tissues (P<0.05). In cultured cells, Bcl-2 expression level was also potentiated after knock-down of miR-143, while those cells with miR-143 over-expression had depressed Bcl-2 levels. Those cells transfected with miR-143 mimics had higher percentage of apoptotic cells. MiR-143 can regulate the expression of Bcl-2 gene in osteosarcoma cells, and mediate the apoptotic process, thereby playing a critical role in the pathogenesis of osteosarcoma. PMID- 26823740 TI - E-cadherin maintains the activity of neural stem cells and inhibits the migration. AB - Cadherins are important adhesion molecules that mediate adhesions and communications between cells. These molecules participate in the formation and maintenance of multicellular organisms including the stem cells. E-cadherin is one of the classic cadherins which is reported to be essential for the survival and self-renewal of embryonic stem cells. Moreover, it could induce cell proliferation inhibitory signaling to regulate cell proliferation. In our study, we over-expressed and silenced E-cadherin in NSCs by lentiviral ways. Transgenic cells were confirmed by both quantitative RT-PCR and western blot. Results of MTT assay showed that over-expression of E-cadherin could enhance the cell activity. Furthermore, we performed Transwell chamber assay to analyze its role in regulation of cell migration. The results showed that the migration percent of over-expression cells was lower than control. Our results indicated that E caherin would maintain the stemness of NSCs and reduce cells migration. PMID- 26823741 TI - Level of circulated microRNA-421 in gastric carcinoma and related mechanisms. AB - As one of the most popular and deadly malignant tumors, gastric cancer still has difficulty in early-diagnosis. Recently the level of circulated DNA related with tumors can be used for diagnosis. MicroRNA-421 (miR-421) has been found to be up regulated in tumor cells. Whether peripheral miR-421 can be used as a marker for diagnosis of gastric carcinoma, however, remains unclear. The expression level of miR-421 in both gastric cancer and normal people were firstly quantified. We then performed in vitro transfection of gastric carcinoma cell line to potentiate or silence miR-421 level. Cell apoptosis and apoptotic protein levels were quantified by flow cytometry and Western blotting, respectively. MiR-421 level in the peripheral blood of gastric cancer patients was significantly elevated. In gastric cancer cell line, the up-regulation of miR-421 significantly inhibited cell apoptosis. The silencing of miR-421 promoted cell apoptosis. Such anti apoptotic role of miR-421 was accomplished by inhibiting caspase 3, up-regulating Bcl-2 and inhibiting Bax. MiR-421 was up-regulated in both tumor tissue and peripheral blood, and can modulate cell apoptosis. Circulated miR-421 can work as a serological marker for early diagnosis of gastric cancer. PMID- 26823742 TI - Methylation-silencing RCC1 expression is associated with tumorigenesis and depth of invasion in gastric cancer. AB - INTRODUCTION: Regulator of chromosome condensation 1 (RCC1) is a critical cell cycle regulator. We firstly identified RCC1 gene hypermethylation in gastric tumor tissues using the differential methylation hybridization (DMH) microarray, but the role of RCC1 in the pathogenesis of gastric carcinoma is largely unknown. METHODS: Three gastric cancer cell lines (AGS, MKN45, and TSGH9201) were used to analyze RCC1 gene methylation, mRNA and protein expressions. Furthermore, 85 pairs of matched human gastric carcinoma samples in a tissue microarray were used to analyze RCC1 expression by immunohistochemistry staining. RESULTS: A differential methylation pattern was found in TSGH9201 (100%), MKN45 (87%), and AGS (62%) cell lines at the 9th CpG site of RCC1 exon 1. RCC1 mRNA and protein expressions in AGS cells were significantly higher than in TSGH9201 and MKN45 cell lines (P < 0.05). Tissue array data showed that RCC1 expression was detected in 21% (18/85) of gastric carcinoma tissues and in 80% (76/95) of adjacent non tumor tissues. The expression of RCC1 in gastric carcinoma tissues was significantly lower than in adjacent non-tumor tissues (P < 0.001). Furthermore, an association between RCC1 expression and clinicopathological features showed that RCC1 expression was closely correlated with tumor differentiation and depth of invasion (P < 0.05). CONCLUSIONS: Our data indicate that RCC1 expression is frequently lost in poorly differentiated gastric cell lines and gastric carcinoma tissues. Loss of RCC1 expression is correlated with tumor differentiation and depth of invasion. These findings suggest that RCC1 may play a tumor suppressor role in gastric carcinoma. PMID- 26823743 TI - Microenvironmental interactions and expression of molecular markers associated with epithelial-to-mesenchymal transition in colorectal carcinoma. AB - The tumor microenvironment is known to play a critical role in tumor progression, invasion and metastasis. The epithelial-to-mesenchymal transition (EMT) is understood as a process of tumor invasion and metastasis. Therefore, we investigated the relation between the EMT and the microenvironment of colorectal carcinoma (CRC). The histological features and expression of EMT markers in tumor cells and surrounded stromal cells were obtained from the surgically resected tissues of 39 patients using microscopic review and immunohistochemistry. The loss of expression of E-cadherin was more prominent in the invasive front of tumor than the surface, where alpha-smooth muscle actin-positive carcinoma associated fibroblasts (CAFs) are accumulated. The signaling molecules of the Wnt and TGF-beta1-Smad pathway were expressed more frequently in the tumor cells and/or CAFs of the invasive margin than those of the tumor surface. The expressions of related transcription factors, such as SNAIL and ZEB1, were increased in the tumor cells and CAFs. The process of EMT may be activated in the tumor margin of CRC under the control of CAFs. Related signaling molecules and transcription factors might be induced by paracrine effects of the surrounding CAFs. PMID- 26823744 TI - CD44v6 down-regulation is an independent prognostic factor for poor outcome of colorectal carcinoma. AB - We aim to investigate the variation of CD44v6 expression in the normal-adenoma primary carcinoma-liver metastasis sequence and its prognostic impact on colorectal carcinomas. The difference in CD44v6 expression between the tumor center and invasive front was also assessed. Immunohistochemistry was performed for CD44v6 on two cohorts. The first was tissue microarrays including 402 primary CRCs sampled from the tumor center and the invasive margin. The second was whole tissue sections, consisting of 217 adenomas, 72 primary carcinomas, and the corresponding metastatic carcinomas. In the first cohort, we found that CD44v6 down-regulation was inclined to lymph node metastasis and perineural invasion, and had an unfavorable prognosis compared with CD44v6 up-regulation. In the second cohort, CD44v6 expression was predominant in adenoma over primary carcinoma and liver metastasis in multiple steps (normal < adenoma > primary carcinoma and liver metastasis). In addition, our analysis showed that CD44v6 expression was decreased at the invasion front of the CRC compared with the center of the tumor. In conclusion, the maximal expression of CD44v6 in adenoma plays a crucial role in colorectal carcinogenesis, while loss of CD44v6 expression on the cell surface of the tumor edge enhances the progression of metastasis. CD44v6 down-regulation is an independent prognostic factor for strikingly worse disease-specific survival. PMID- 26823745 TI - Echistatin prevents posterior capsule opacification in diabetic rabbit model via integrin linked kinase signaling pathway. AB - PURPOSE: To investigate the effect of disintegrin echistatin on integrin linked kinase (ILK) and subsequent PI3-K/Akt and ERK1/2 signaling pathways in the posterior capsule opacification (PCO) model of diabetic rabbit. METHODS: 56 rabbits were injected alloxan to model diabetic. Then they accepted lens extraction surgery and randomly and intraoperatively injected distilled water (control group; n = 28) or 10.0 mg.L(-1) echistatin (echistatin-treated group; n = 28) into the anterior chamber. Each group was subdivided into ten days group (n = 14) and six weeks group (n = 14) respectively. The PCO severity was evaluated with a slit lamp microscope and light microscope for 10 days and 6 weeks postoperatively. The levels of ILK in the posterior capsule were determined by Q PCR, Western blotting and Immunohistochemistry. Akt and ERK1/2 phosphorylation were analyzed by Western blotting. RESULTS: 10 days and 6 weeks after surgery, the grades of PCO in the echistatin-treated group were lower than the control group. The lens epithelial cells (LECs) in the posterior capsule of echistatin treated eyes had decreased degrees of proliferation and migration than the control group. And no significant side effects appeared after treated with echistatin. Echistatin could significantly reduce the expression of ILK in terms of both mRNA and protein levels. The phosphorylation levels of Akt and ERK1/2 were decreased in the echistatin-treated group compared with the control group. CONCLUSIONS: Echistatin could inhibit postoperative PCO occurrence and development in diabetic rabbit eyes, which may be related to down-regulation the expression of ILK and inhibition the PI3-K/Akt and ERK1/2 pathways. PMID- 26823746 TI - Low tidal volume with PEEP and recruitment expedite the recovery of pulmonary function. AB - The potentially harmful effects of short-term mechanical ventilation during surgery have been examined in recent years. An optimal strategy for mechanical ventilation of patients during non-laparoscopic abdominal surgery must be devised. A total of 63 patients undergoing elective open abdominal surgery with more than 2 h of ventilation time were selected for this randomized, open-label, clinical study. They were divided into three ventilation groups: high volume of 9 ml/kg IBW (ideal body weight) with ZEEP (zero end-expiratory pressure); low volume of 7 ml/kg IBW with 8 cm H2O PEEP (positive end expiratory pressure); and low volume of 7 ml/kg IBW with 8 cm H2O PEEP and recruitment. Intraoperative PaO2/FiO2 ratio and pulmonary compliance and postoperative pulmonary function were measured. There were no significant differences in intraoperative PaO2/FiO2 ratio among the three groups (P=0.31). The pulmonary compliance of three groups showed different changes over time (group effect over time P=0.0006). There were no significant differences in FEV1 or FVC among the three groups (P=0.32 and 0.09, respectively), but both of these measurements showed different changes over time (group effect over time P<0.001). On the first postoperative day, the low volume with high PEEP and recruitment group had significantly higher FEV1 than the other two groups (mean +/- SD): 1.52 +/- 0.37 versus 0.95 +/- 0.38 (P<0.001) and 1.52 +/- 0.37 versus 0.95 +/- 0.34 (P<0.001), respectively. Low tidal volume with PEEP and recruitment showed advantages in maintaining the pulmonary compliance and expediting the recovery of the 1(st) postoperative day's pulmonary function in patients undergoing non-laparoscopic abdominal surgery. PMID- 26823747 TI - Roles of Cx43 and AKAP95 in ovarian cancer tissues in G1/S phase. AB - OBJECTIVE: The purpose of this study was to investigate the expression of A kinase anchor protein 95 (AKAP95), cell cycle protein E1 (cyclinE1) and D1 (cyclinD1), and gap junction protein connexin 43 (Cx43) in ovarian cancer tissues, the relationship between four proteins and clinicopathologic parameters, and the correlation between these proteins. METHODS: The expression of proteins in 54 cases of ovarian cancer tissues was detected by immunohistochemical method. RESULTS: The positive expression rates of AKAP95, cyclinD1 and cyclinE1 in ovarian cancer tissues were 72.22%, 66.67% and 79.63%, respectively, which were higher than that of ovarian pericarcinoma tissues expressing as 33.33%, 25% and 8.30% (P<0.05). The positive expression rate of Cx43 in ovarian cancer tissues was 40.74%, which was lower than that of ovarian pericarcinoma tissues expressing as 75%; respectively, and the difference was statistically significant between groups (P<0.05). The expression of cyclinD1 in ovarian cancer tissues was related to the histologic type (P<0.05) while it showed no correlation with the degree of differentiation (P>0.05). Additionally, the expression of AKAP95, Cx43 and cyclinE1 in ovarian cancer tissues showed no correlation with the degree of differentiation or the histologic type (P>0.05). Protein expressions of AKAP95, Cx43 and cyclinE1 were correlated with each other (P<0.05), and the expressions of cyclinD1, cyclinE1 and Cx43 were also correlated with each other (P<0.05). However, AKAP95 and cyclinD1 showed no correlation (P>0.05). CONCLUSION: AKAP95, cyclinD1 and cyclinE1 play an important role in promoting the process of ovarian cancer formation. The tumor inhibitory effects of Cx43 protein on the pathogenesis of ovarian cancer were weakened. The expression of cyclinD1 in ovarian cancer tissues is related to the histologic type while it shows no correlation with the degree of differentiation. Additionally, the expression of AKAP95, Cx43 and cyclinE1 in ovarian cancer tissues shows no correlation with the degree of differentiation or the histologic type. AKAP95 expression is correlated with Cx43 and cyclinE1 expression; Cx43 expression is correlated with AKAP95, cyclinD1 and cyclinE1 expression; cyclinE1 expression is correlated with AKAP95, Cx43, cyclinD1 expression; cyclinD1 expression is correlated with Cx43 and cyclinE1 expression, while AKAP95 and cyclinD1 show no correlation. PMID- 26823748 TI - Expression of uPAR in human trophoblast and its role in trophoblast invasion. AB - Placental trophoblast cells differentiate into invasive trophoblasts or syncytiotrophoblasts. Abnormal trophoblast invasion results in pregnancy associated disease and abortion. uPAR is a cell membrane-bound glycosylated protein, involved in physiological and pathological processes. However, uPAR expression in villi during threatened abortion and its role in trophoblast differentiation are unclear. We determined that, uPAR expression in the villi was reduced in threatened abortion patients than that in normal pregnancy. uPARsiRNA inhibited the potential for trophoblast migration and invasion in explants culture and HTR8/SVneo cells. It also enhanced forskolin-induced fusion of HTR8/SVneo cells. Overall, this study provides a possible reason for abortion. PMID- 26823749 TI - Downregulation of miR-129 in peripheral blood mononuclear cells is a diagnostic and prognostic biomarker in prostate cancer. AB - OBJECTIVE: The present study was designed to explore the clinical values of microRNA-129 (miR-129) expression in peripheral blood mononuclear cells for prostate cancer patients and the role of miR-129 in the proliferation of prostate cancer. METHODS: The peripheral blood mononuclear cells were isolated form blood simple from 98 patients confirmed with prostate cancer and 56 matched healthy volunteers. Reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression level of miR-129 in peripheral blood mononuclear cells. Cox proportional hazards regression models and Kaplan-Meier analysis were used to evaluate the association of miR-129 expression with clinical and pathological characteristics of prostate cancer patients. The effect of miR-129 on the proliferation of prostate cancer cells in vitro was also determined. RESULTS: Reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) results showed that the expression of miR-129 was dramatically down-regulated in peripheral blood mononuclear cells for prostate cancer patients in comparison with healthy controls (P<0.05). The decrease in miR-129 expression in peripheral blood mononuclear cells was significantly associated with aggressive clinical pathological features such as histological grade (P=0.010), high preoperative PSA level (P=0.002), pathological stage (P=0.011), high Gleason score (P=0.005), lymph node metastasis (P=0.002), angiolymphatic invasion (P=0.004), biochemical recurrence (P=0.001). The prostate cancer patients with a low miR-129 expression in peripheral blood mononuclear cells had an obviously shorter BCR-free survival compared with high miR-129 expression (P<0.001). The Cox multivariate analysis established that the miR-129 expression may be an independent prognostic factor for biochemical recurrence (BCR)-free survival prostate cancer patients (P=0.000). The results of in vitro CCK-8 assays, as well as proliferating cell nuclear antigen (PCNA) and phosphorylated histone-3 (P-H3) (markers of proliferation) indicated that miR-129 overexpression markedly retarded the proliferation of PC-3 and DU-145 cells. CONCLUSIONS: Our results provide the first evidence that the miR-129 is significantly downregulated in prostate cancer patients and multivariate analysis confirmed that miR-129 is a novel independent prognostic factor for prostate cancer. Overexpression of miR-129 exerts tumor suppressive functions and abrogates prostate cancer growth. PMID- 26823750 TI - Cinnamaldehyde attenuates pressure overload-induced cardiac hypertrophy. AB - BACKGROUND: Cinnamaldehyde is a major bioactive compound isolated from the leaves of Cinnamomum osmophloeum. Studies have demonstrated that cinnamaldehyde has anti bacterial activity, anti-tumorigenic effect, immunomodulatory effect, anti-fungal activity, anti-oxidative effect, anti-inflammatory and anti-diabetic effect. It has been proven that Cinnamaldehyde improves ischemia/reperfusion injury of pre treatment. However, little is known about the effect of cinnamaldehyde on cardiac hypertrophy. METHODS: Aortic banding (AB) was performed to induce cardiac hypertrophy in mice. Cinnamaldehyde premixed in diets was administered to mice after one week of AB. Echocardiography and catheter-based measurements of hemodynamic parameters were performed at week 7 after starting cinnamaldehyde (8 weeks after surgery). The extent of cardiac hypertrophy was evaluated by pathological and molecular analyses of heart samples. Meanwhile, the effect of cinnamaldehyde on myocardial hypertrophy, fibrosis and dysfunction induced by AB was investigated, as was assessed by heart weigh/body weight, lung weight/body weight, heart weight/tibia length, echocardiographic and haemodynamic parameters, histological analysis, and gene expression of hypertrophic and fibrotic markers. RESULTS: Our data demonstrated that echocardiography and catheter-based measurements of hemodynamic parameters at week 7 revealed the amelioration of systolic and diastolic abnormalities by cinnamaldehyde intervention. Cardiac fibrosis in AB mice was also decreased by cinnamaldehyde. Moreover, the beneficial effect of cinnamaldehyde was associated with the normalization in gene expression of hypertrophic and fibrotic markers. Further studies showed that pressure overload significantly induced the activation of extracellular signal regulated kinase (ERK) signaling pathway, which was blocked by cinnamaldehyde. CONCLUSION: Cinnamaldehyde may be able to retard the progression of cardiac hypertrophy and fibrosis, probably via blocking ERK signaling pathway. PMID- 26823751 TI - Effect of Bisphenol A on invasion ability of human trophoblastic cell line BeWo. AB - Bisphenol A (BPA) is a kind of environmental endocrine disruptors (EEDs) that interfere embryo implantation. Trophoblast invasion plays a crucial role during embryo implantation. In this study, the effects of BPA on invasion ability of human trophoblastic cell line BeWo and its possible mechanism were investigated. BeWo cells were exposed to BPA and co-cultured with human endometrial cells to mimic embryo implantation in transwell model. The proliferation and invasion capability of BeWo cells were detected. The expression of E-cadherin, DNMT1, MMP 2, MMP-9, TIMP-1 and TIMP-2 were also analyzed. The results showed that the invasion capability of BeWo was reduced after daily exposure to BPA. BPA had biphasic effect on E-cadherin expression level in BeWo cells and expression level of DNMT1 was decreased when treated with BPA. Moreover, BPA treatment also changed the balance of MMPs/TIMPs in BeWo cells by down-regulating MMP-2, MMP-9 and up-regulating TIMP-1, TIMP-2 with increasing BPA concentration. Taken together, these results showed that BPA treatment could reduce the invasion ability of BeWo cells and alter the expression level of E-cadherin, DNMT1, TIMP 1, TIMP-2, MMP-2, and MMP-9. Our study would help us to understand the possible mechanism of BPA effect on invasion ability of human trophoblastic cell line BeWo. PMID- 26823752 TI - Survival prognosis and clinicopathological features of the lymph nodes along the left gastric artery in gastric cancer: implications for D2 lymphadenectomy. AB - The Japanese Gastric Cancer Treatment Guidelines (third edition) have assigned No. 7 station left gastric artery lymph nodes (LNs) to the D1 range of lymphatic dissection. We investigated the clinicopathological characteristics, survival impact, and appropriateness of ascribing No. 7 station LNs to D1 lymphadenectomy in gastric cancer. Patients (n=608) undergoing radical resection with No. 7 station LN dissection were recruited between January 1997 and June 2008. They were subdivided into four groups: N0, no LN metastasis; D1, LN without No. 7 station LN metastasis in the D1 lymphadenectomy region; No. 7, No. 7 station LN without LN metastasis in the D2 lymphadenectomy region; and D2, LN without No. 7 station LN metastasis in the D2 lymphadenectomy region. Of these, 17.2% (n=105) were positive for No. 7 LN metastasis, an important, independent prognostic factor associated with poor clinicopathological parameters, advanced tumor stage, and reduced survival. Tumor behavior in the No. 7 group was similar to that in the D2 group, but poorer than in the D1 group in terms of advanced tumor stage, with 5-year survival rates of 34.3%, 25.9% and 54.6%, respectively. Five-year survival rates in the No. 7 group were comparable to those in the D2 group (P>0.05), but significantly lower than in the D1 group (P<0.05). Logistic multivariate regression analysis established No. 3 and 9 station LN metastasis, node classification, and tumor-node-metastasis stage as independent risk factors for No. 7 station LN metastasis. Thus, No. 7 station LNs should be ascribed to D2 lymphadenectomy in gastric cancer. PMID- 26823753 TI - MiR-155 modulates the progression of neuropathic pain through targeting SGK3. AB - This study aimed to illustrate the potential effects of miR-155 in neuropathic pain and its potential mechanism. Spragure-Dawley (SD) rats were used for neuropathic pain model of bilateral chronic constriction injury (bCCI) construction. Effects of miR-155 expression on pain threshold of mechanical stimuli (MWT), paw withdrawal threshold latency (PMTL) and cold threshold were analyzed. Target for miR-155 was analyzed using bioinformatics methods. Moreover, effects of miR-155 target gene expression on pain thresholds were also assessed. Compared with the controls and sham group, miR-155 was overexpressed in neuropathic pain rats (P<0.05), but miR-155 slicing could significantly decreased the pain thresholds (P<0.05). Serum and glucocorticoid regulated protein kinase 3 (SGK3) was predicted as the target gene for miR-155, and miR-155 expression was negatively correlated to SGK3 expression. Furthermore, SGK3 overexpression could significantly decreased the pain thresholds which was the same as miR-155 (P<0.05). Moreover, miR-155 slicing and SGK3 overexpression could significantly decrease the painthreshold. The data presented in this study suggested that miR 155 slicing could excellently alleviate neuropathic pain in rats through targeting SGK3 expression. miR-155 may be a potential therapeutic target for neuropathic pain treatment. PMID- 26823754 TI - HRP-3 protects the hepatoma cells from glucose deprivation-induced apoptosis. AB - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. It is important for HCC cells to resist to apoptosis caused by adverse energy pressure in microenvironment during the HCC tumorigenesis. HRP-3, a member of hepatoma-derived growth factor (HDGF)-related proteins (HRP) family, was shown to be highly up-regulated in HCC tissues and play an important role in HCC pathogenesis based on our previous research. The aim of the study was to investigate the HRP-3's role in HCC cells endurance against energy pressure. METHOD: The HRP-3 expression level in primary rat hepatocytes and human HCC cell lines were examined when changing the extracellular glucose concentration. To assess biological function of HRP-3 during glucose deprivation, HRP-3 stable knockdown and control clones of SMMC-7721 and SK-hep1 were constructed for further analysis including cellular morphology observation, apoptotic sub G1 peak analysis and the mTOR-mediated phosphorylation of S6K1 detection in the absence of glucose. RESULTS: Expression level of HRP-3 protein was highly up-regulated both in primary rat hepatocytes and HCC cells as prolonging the stimulation of glucose deprivation. Both morphology and sub-G1 phase analyses indicated that stable knockdown of HRP-3 sensitized HCC cells to glucose deprivation-induced cell apoptosis. Furthermore, silence of HRP-3 prevented the de-phosphorylation of S6K1 induced by glucose deprivation, which was an essential molecular event for HCC cell survival in energy pressure. CONCLUSIONS: We propose that glucose deprivation-induced HRP-3 up-regulation potentially plays a major role in protecting HCC cells against apoptosis caused by energy pressure. PMID- 26823755 TI - Elevated expression of MDR1 associated with Line-1 hypomethylation in esophageal squamous cell carcinoma. AB - BACKGROUND: The aim is to discuss the relationship of Line-1 methylation and the MDR1 expression in esophageal squamous cell carcinoma (ESCC). METHODS: We analyzed the methylation level of Line-1 by quantitative real-time MSP, and the expression of MDR1 by real-time RT-PCR in 310 ESCC and corresponding non-tumor tissues. RESULTS: We found that the methylation index (MI) of Line-1 decreased from 0.90 in non-tumor tissues toward 0.78 in ESCC. The cumulative survival was significantly shorter in ESCC patients with MI <= 0.78 (34 months) than that in patients with MI > 0.78 (43 months). There was a statistical difference between MI <= 0.78 and MI > 0.78 cases with these clinicopathologic parameters (age, AJCC stage, differentiation; P = 0.010, P < 0.0001, P = 0.015, respectively). These results implied that Line-1 hypomethylation could be more in ESCC patients with older, advanced tumor and poor differentiation group. Meanwhile, ESCC with demethylation of Line-1 were shown elevated MDR1 expression in tumor (Mean-??Ct = 0.21), but ESCC with hypermethylation of Line-1 were considered to be decreased MDR1 expression in tumor (Mean-??Ct = -0.86). CONCLUSIONS: Line-1 hypomethylation could be as a biomarker of poor prognosis in ESCC patients. MDR1 gene could be activated via epigenetic mechanisms with demethylation of Line-1 in ESCC, and enhance tumor progression. PMID- 26823756 TI - MicroRNA-141 inhibits vascular smooth muscle cell proliferation through targeting PAPP-A. AB - It is well known that ox-LDL plays key roles in the development of atherosclerosis, partly by inducing vascular smooth muscle cells (VSMCs) proliferation. Recent findings have revealed that microRNAs, a class of small noncoding RNAs, could regulate cell proliferation in many physiological and pathological conditions. However, the role and function of miRNAs on ox-LDL induced VSMC proliferation are not fully elucidated. In this study, we showed that ox-LDL could suppress miR-141 expression and inhibition of miR-141 could promote VSMCs proliferation. Moreover, we found that PAPPA was the direct target gene of miR-141. Overexpression of PAPPA impaired the miR-141-induced inhibition of proliferation in the VSMCs. Taken together; miR-141 may play important roles in ox-LDL-induced abnormal proliferation of the VSMC. PMID- 26823757 TI - Identification of phosphorylated MYL12B as a potential plasma biomarker for septic acute kidney injury using a quantitative proteomic approach. AB - Acute kidney injury (AKI) is a common and increasingly encountered complication in hospitalized patients with critical illness in intensive care units (ICU). According to the etiology, Sepsis-induced AKI (SAKI) is a leading contributor to AKI and significantly has very poor prognosis, which might be related to the late detection when the elevation of BUN and serum creatinine (SCr) is used. Many genes are up-regulated in the damaged kidney with the corresponding protein products appearing in plasma and urine. Some of these are candidate biomarkers for more timely diagnosis of SAKI. Therefore, extensive research efforts over this past decade have been directed at the discovery and validation of novel SAKI biomarkers to detect injury prior to changes in kidney function, a number of serum and urinary proteins, including NGAL, KIM-1, cystatin-C, IL-18, and L-FABP, have been identified for predicting SAKI before a rise in BUN and serum creatinine in several experimental and clinical trainings. Unfortunately, an ideal biomarker of SAKI with highly sensitivity and specificity has not been identified yet. Recent progresses in quantitative proteomics have offered opportunities to discover biomarkers for SAKI. In the present study, kidney tissue samples from SAKI mice were analyzed by two-dimensional differential gel electrophoresis (2D-DIGE), and 4 up-regulated proteins, which were actin (ACTB), myosin regulatory light chain 12B (MYL12B), myosin regulatory light polypeptide 9 (MYL9), and myosin regulatory light chain 12A (MYL12A) were identified by matrix assisted laser desorption ionization-time of flight/time of flight mass spectrometry (MALDI-TOF/TOF MS). Among all the varied proteins, MYL12B was validated by western blot. Interestingly, there was no change between the SAKI and control kidney tissues, however, phosphorylated MYL12B was detected to be consistent with the proteomics data. Furthermore, phosphorylated MYL12B was found similarly to be increased in SAKI plasma, while MYL12B was changeless in plasma of control group. Taking together, phosphorylated MYL12B may be employed as a potential plasma biomarker for the early diagnosis of SAKI. PMID- 26823758 TI - Persistent hyperinsulinemic hypoglycemia of infancy: a clinical and pathological study of 19 cases in a single institution. AB - OBJECTIVE: To study the clinical and pathological features of persistent hyperinsulinemic hypoglycemia of infancy. METHOD: The clinical and pathological data of 19 cases of persistent hyperinsulinemic hypoglycemia of infancy were retrieved and reviewed from the medical records in Children's Hospital of Fudan University. RESULTS: There were 13 boys and 6 girls. The age interval was from 16 days to 7 months, and the average age was 2.71 +/- 2.23 months. The blood glucose concentrations ranged from 0.57 to 3.0 mmol/L (average value 1.60 +/- 0.75 mmol/L) and the serum insulin concentrations ranged from 3.1 to 79.4 uIU/ml (average value 27.89 +/- 21.81 uIU/ml) at the time of one week before operation. The size of lesion was between 2 cm to 6.5 cm in maximum diameter (average value 4.04 +/- 1.18 cm). 19 cases were divided into three types according to the pathological classification criteria: focal type (1 case), diffuse type (17 cases) and atypical type (1 case). The enucleation of the nodule was given for the patient of focal type and subtotal pancreatectomy was administrated for diffuse and atypical type patients. The blood glucose concentrations ranged from 3.0 to 12.4 mmol/L (average value 6.21 +/- 2.69 mmol/L) at the time of one month after operation. The difference between the preoperative blood glucose concentrations and the postoperative blood glucose concentrations was statistically significant (1.6037 +/- 0.7458 mmol/L vs. 6.2105 +/- 2.6882 mmol/L, P<0.05). Insulin was positive for the multiple pancreatic islets, and the ki-67 index was between 5% and 8%. P57(kip2) was negative. 19 patients were followed up for a period of 2 to 38 months. 13 cases recovered well without any complications, and 6 cases had postoperative hyperglycemia and need a medication to control the blood glucose concentrations. CONCLUSION: Persistent hyperinsulinemic hypoglycemia of infancy mainly occurred in infants. Boys had the predominance and the most common pathological type was the diffuse type. The different surgical methods (focal type with lesion enucleation, diffuse and atypical type with subtotal pancreatectomy), were effective for different patients, and most of patients had a good prognosis. Early diagnosis and appropriate treatment to maintain euglycemia remained the mainstay of management to prevent postoperative complications. Therefore, the correct pathological classification could help clinicians to find effective treatment and improve the outcome. PMID- 26823759 TI - Effect of ITGA5 down-regulation on the migration capacity of human dental pulp stem cells. AB - BACKGROUND: The purpose of this study was to evaluate the role of integrin-alpha5 (ITGA5) in regulating the migration capacity of human dental pulp stem cells (hDPSCs), which might provide new evidence for understanding the repair and regeneration mechanisms of dental pulp tissues. MATERIALS AND METHODS: The enzyme digestion method was employed to isolate the hDPSCs from dental pulp tissues. The cell surface markers of hDPSCs were detected using flow cytometry analysis. Then the colony forming and multi-differentiation capacity of hDPSCs were evaluated. The lentivirus vector that carried the ITGA5 shRNA was constructed and real-time PCR was used to examine the effectiveness of ITGA5 shRNA lentivirus. Then transwell assay was performed to evaluate the impact of ITGA5 inhibition on the migration capability of hDPSCs. RESULTS: Our results showed that the cells we isolated from the dental pulps were positive for mesenchymal stem cells biomarkers. In addition, the cells possessed both colony forming capacity and multi-differentiation potential. ITGA5 shRNA lentivirus could not only infect hDPSCs with high efficiency, but also down-regulate the expression level of ITGA5 mRNA significantly (P<0.01). The transwell assay revealed the number of cells that migrated to the lower chamber was significantly less in the ITGA5 shRNA group compared with that in the scrambled shRNA group (P=0.016). CONCLUSION: ITGA5 plays an important role in maintaining and regulating the normal migration capacity of hDPSCs. PMID- 26823760 TI - Mechanism of IFN-gamma in regulating OPN/Th17 pathway during vascular collagen remodeling of hypertension induced by ANG II. AB - More and more researches show that hypertensive vascular remodeling is closely related to the imbalance of immune system in recent years. IFN-gamma is natural protein with the function of immune regulation and has resistance effect on vascular remodeling. However, the mechanism of IFN-gamma is to be defined. This paper is to explore the mechanism of IFN-gamma in regulating OPN/Th17 pathway. In this research, animal models of vascular collagen remodeling were established by inducing hypertensive mice with ANG II. There was no statistical significance when the systolic blood pressures and the percentages of wall thickness/lumen diameter in both groups of WT + AngII + IFN-gamma and WT + PBS were compared (P=0.219>0.05, P=0.118>0.05). The concentration of serum precollagen-type I and III and their ratio in WT + AngII + IFN-gamma group were decreased after the IFN gamma being given (P<0.01). Expression of OPN within tissue in WT + Ang II group was relatively high, but lowered after treated by IFN-gamma. Th17 cell ratio was decreased in WT + AngII + IFN-gamma group (P<0.01). Expressions of RORalpha and RORgammat mRNA within Th17 cell were decreased (P<0.01). The content of IL-23 in WT + AngII + IFN-gamma group was increased, while IL-10 and TGF-beta decreased. It has proved that IFN-gamma can regulate the hypertensive vascular collagen remodeling induced by ANG II, lower the systolic pressure and reduce the pathological damage of vascular collagen remodeling and the collagen synthesis. The mechanism may that the differentiation of Th17 is inhibited by suppressing the OPN expression and regulating the secretion of inflammatory cytokines. PMID- 26823761 TI - Pyruvate kinase, muscle isoform 2 promotes proliferation and insulin secretion of pancreatic beta-cells via activating Wnt/CTNNB1 signaling. AB - Failure of pancreatic beta-cells is closely associated with type 2 diabetes mellitus (T2DM), an intractable disease affecting numerous patients. Pyruvate kinase, muscle isoform 2 (PKM2) is a potential modulator of insulin secretion in beta-cells. This study aims at revealing roles and possible mechanisms of PKM2 in pancreatic beta-cells. Mouse pancreatic beta-cell line NIT-1 was used for high glucose treatment and PKM2 overexpression by its specific expression vector. Cell proliferation by Thiazolyl blue assay, cell apoptosis by annexin V-fluorescein isothiocyanate/prodium iodide staining and insulin secretion assay by ELISA were performed in each group. The mRNA and protein levels of related factors were analyzed by real-time quantitative PCR and western blot. Results showed that Pkm2 was inhibited under high glucose conditions compared to the untreated cells (P < 0.01). Its overexpression significantly suppressed NIT-1 cell apoptosis (P < 0.01), and induced cell proliferation (P < 0.05) and insulin secretion (P < 0.05). Related factors showed consistent mRNA expression changes. Protein levels of beta-catenin (CTNNB1), insulin receptor substrate 1 (IRS1) and IRS2 were all promoted by PKM2 overexpression (P < 0.01), indicating the activated Wnt/CTNNB1 signaling. These results indicated the inductive roles of PKM2 in pancreatic beta cell NIT-1, including promoting cell proliferation and insulin secretion, and inhibiting cell apoptosis, which might be achieved via activating the Wnt/CTNNB1 signaling and downstream factors. This study offers basic information on the role and mechanism of PKM2 in pancreatic beta-cells, and lays the foundation for using PKM2 as a potential therapeutic target in T2DM. PMID- 26823762 TI - The role of TAK1 expression in thyroid cancer. AB - OBJECTIVE: To investigate the expression, significance, and role of transforming growth factor beta-activated kinase 1 (TAK1) in human thyroid cancer tissue. METHODS: The data of 101 patients with thyroid cancer who underwent surgical treatment at our hospital from June 2001 to March 2010 were collected. All the patients were diagnosed with thyroid cancer by post-operative pathological examination. Immunohistochemistry staining was performed to detect the expression of TAK1 protein in thyroid cancer tissue and the adjacent tissues, and correlation analysis was performed to explore the relationships between TAK1 expression level and clinical and pathological features and the patient's prognosis. In addition, thyroid cancer cells (BCPAP) were cultured in vitro to investigate the role of TAK1 in the proliferation, invasion, and apoptosis of thyroid cancer cells and the possible mechanisms of its action. RESULTS: The TAK1 expression rate was 78.2% in human thyroid cancer tissue, which was significantly higher than in the adjacent normal tissues (14.9%) (P < 0.05). The TAK1 expression level was unrelated to the patient's age, gender, and histological type (P > 0.05) and was closely related to the clinical stage and lymph node metastasis (P < 0.05). Moreover, the five-year survival rate of patients with TAK1 expression was significantly lower than those without TAK1 expression (P = 0.019). In vitro, 5Z-7-oxozeaenol, a selective TAK1 inhibitor, significantly inhibited the proliferation and invasion and promoted the apoptosis of thyroid cancer cells, possibly due to its inhibition of the activation of the nuclear factor-kappaB (NF-kappaB) signaling pathway. CONCLUSION: TAK1 may be an important factor involved in the pathogenesis of thyroid cancer, and targeted down regulation of TAK1 may improve the prognosis of patients with thyroid cancer. PMID- 26823763 TI - Development of an improved animal model of experimental autoimmune myositis. AB - Multiple animal models of experimental autoimmune myositis (EAM) have been developed. However, these models vary greatly in the severity of disease and reproducibility. The goal of this study was to test whether vaccination twice with increased dose of rat myosin and pertussis toxin (PT) could induce EAM with severer disease in mice. BALB/c mice were injected with 1 mg rat myosin in 50% complete Freund's adjuvant (CFA) weekly for four times and one time of PT (EAM) or twice with 1.5 mg myosin in CFA and PT (M-EAM). In comparison with that in the CFA and PT injected controls, vaccination with rat myosin and injection PT significantly reduced the muscle strength and EMG duration, elevated serum creatine kinase levels, promoted inflammatory infiltration in the muscle tissues, leading to pathological changes in the muscle tissues, demonstrating to induce EAM. Interestingly, we found that vaccination twice with the high dose of myosin and PT prevented EAM-related gain in body weights and caused significantly less muscle strength in mice. More importantly, all of the mice receiving high dose of myosin and PT survived while 3 out of 16 mice with four times of low dose of myosin died. Finally, vaccination with high dose of myosin promoted CD4(+) and CD8(+) T cell infiltration in the muscle tissues and up-regulated MHC-I expression in the muscle tissues of mice. Hence, the new model of EAM is a time saving, efficient and easily replicable tool for studying autoimmune myositis. PMID- 26823764 TI - MiR-124 effect in neurons apoptosis in newborn rat with thyroid hypofunction. AB - Congenital thyroid hypofunction can cause a variety of developmental disorders. Hippocampus is an important structure participating in the cognitive activities. Neural function damage is able to induce hippocampal neuron apoptosis. As a miRNA expressed specifically and abundantly in brain tissue, miR-124 has protective effect to neuron apoptosis caused by cerebral apoplexy. However, its role in neuron apoptosis caused by thyroid hypofunction is still unclear. The rats were divided into four groups including normal group, thyroid hypofunction group, miR 124 negative control group, and miR-124 mimics group. Propylthiouracil (50 mg/d) was injected to the stomach to the rats with 15 d pregnancy till the newborn rats were born. Inducing the thyroid hypofunction rat model and then injecting miR-124 mimics to ventricle. Serum TSH, FT3 and FT4 were detected to confirm the model. Immunohistochemistry was carried out to calculate neuron number. Tunel assay was used to detect neuron apoptosis. Western blot was applied to detect apoptosis related protein Caspase-3, Bcl-2 and Bax expression. After brain injection miR 124 mimics, hippocampal neuron number and morphology both improved in 15 d newborn mice compared with thyroid hypofunction group. Tunel staining found positive neurons reduced, which indicated that miR-124 can inhibit hippocampal neuron apoptosis in thyroid hypofunction rats. Further Western blot results revealed that apoptosis inhibition might be related to down-regulating activated Caspase-3 and Bax levels, and up-regulating tumor-suppressor gene Bcl-2 expression. MiR-124 can protect neuron apoptosis in thyroid hypofunction rat. PMID- 26823765 TI - C/EBPalpha inhibits proliferation of breast cancer cells via a novel pathway of miR-134/CREB. AB - C/EBPalpha plays an important role in the modulation of cell proliferation, differentiation or apoptosis in various tissues. Most recently, reduced expression of C/EBPalpha and growth inhibitory effect was found in primary mammary carcinomas. However, the underlying mechanism is still not fully aware. Here, we firstly identified miR-134 as a target of C/EBPalpha in MCF7 breast cancer cell lines. C/EBPalpha overexpression promoted miR-134 expression, causing suppression of apoptosis- protective genes CREB and Bcl-2, and resulted in the proliferation inhibition of MCF7 cells. Moreover, anti-miR-134 rescued the proliferation inhibition of MCF7 cells and the suppression of anti-apoptotic genes CREB and Bcl-2 caused by C/EBPalpha overexpression. Collectively, C/EBPalpha inhibited cell growth in breast cancer cells via a novel pathway miR 134/CREB. PMID- 26823766 TI - Copy number loss of variation_91720 in PIK3CA predicts risk of esophageal squamous cell carcinoma. AB - PURPOSE: Esophageal squamous cell carcinoma (ESCC) is one of the most fatal cancers worldwide. However, the etiology is complex and unclear. 3q26 harboring abundant oncogenes have been identified as the loci of ESCC susceptibility. In the present study, we examined whether CNVs on 3q26 would be associated with the risk, TNM stage and prognosis of ESCC. METHODS: Variation_91720 in phosphatidylinositol 3-kinase catalytic subunit (PIK3CA) and Variation_91733 in sex-determining region Y-box 2 overlapping transcript (SOX2OT) were selected for investigation. The study included 204 ESCC patients and 208 healthy controls. The copy number of the selected sites and mRNA was detected by real-time fluorescence quantitative polymerase chain reaction and calculated using the CopyCaller v2.0 software program. RESULTS: The copy number distribution of Variation_91720 was significantly different in ESCC cases and matched controls (p<0.001). Copy number loss of Variation_91720 may increase the risk of ESCC (OR=6.217, 95% CI=3.117 12.400; adjusted OR =6.251, 95% CI=3.130-12.428). PIK3CA mRNA expression was higher in tumor tissue (P=0.0003) and increased with the copy number gain of Variation_91720. CONCLUSION: Our findings suggest that copy number loss of Variation_91720 in PIK3CA predicts risk of ESCC, which might serve as a biomarker that for early diagnosis of ESCC. PMID- 26823767 TI - Protective effects of berberine on high fat-induced kidney damage by increasing serum adiponectin and promoting insulin sensitivity. AB - Berberine (BBR) has been reported in several studies in cell and animal models. However, the mechanism of actions is not fully understood. The present study was therefore aimed to explore the effects of berberine on insulin sensitivity and kidney damage in a high fat diet rat model. Impaired glucose tolerance rats induced by injection of berberine while fed with high fat laboratory chow. After rats were treated for 4 weeks, OGTT and IPITT were determined. Mass and PAS were used to study the kidney tissue. ELISA was used to detect the protein concentration of CRP and TNF-alpha. Western blot was used to detect the proteins adiponectin, adipoR1, adipoR2 and p-AMPK expression level. These encouraging findings suggest that berberine has excellent pharmacological potential to prevent kidney damage. PMID- 26823768 TI - Effect of prostaglandin reductase 1 (PTGR1) on gastric carcinoma using lentivirus mediated system. AB - Gastric carcinoma is a digestive related malignant tumor with poor diagnosis and prognosis for advanced patients. PTGR1 (prostaglandin reductase 1), as a potential cancer biomarker, has not been reported in gastric carcinoma occurrence. To investigate the role of PTGR1 on gastric carcinoma cells, human PTGR1 was efficiently silenced by lentivirus-mediated system in MGC-803 cells confirmed by quantitative real-time PCR (qRT-PCR) and western blot. Then cell proliferation, colony formation and cell cycle were determined after knockdown of PTGR1 by MTT assay, colony assay and flow cytometry, respectively and data suggested that PTGR1 down regulated MGC-803 cells significantly suppressed the proliferation and colony formation ability and induced cell cycle arrest in the G0/G1 phase compared to controls (P < 0.001). Further investigation demonstrated knockdown of PTGR1 influenced cell proliferation and cell cycle via activating p21 and p53 signaling pathway described by Western blot assay. Our findings indicate that PTGR1 may be an oncogene in human gastric carcinoma and identified as a diagnosis and prognosis target for gastric carcinoma. PMID- 26823769 TI - MicroRNA-96 promotes myocardial hypertrophy by targeting mTOR. AB - As a main cause of cardiac hypertrophy, myocardial hypertrophy includes the proliferation and enlongation of myocardial cell, resulting in abnormally cardiac enlargement. However, the pathogenesis and the molecular mechanism that regulate gene expression of myocardial hypertrophy remain incompletely understood. MiRNAs were deemed as an important molecules involved in a variety of pathological processes. MiR-96 has been reported being associated with the tumor proliferation, but whether miR-96 is involved in cardiac hypertrophy remains uncertain. In this study, we have confirmed that, as the myocardial hypertrophy gene, mTOR was a target gene of miR-96, who would promote the occurrence of myocardial hypertrophy. Thus, we got the conclusion that miR-96 could promote myocardial hypertrophy by inhibiting mTOR, miR-96 and mTOR were negatively correlated. PMID- 26823770 TI - Amiloride suppresses pilocarpine-induced seizures via ASICs other than NHE in rats. AB - BACKGROUND AND PURPOSE: Although recent studies have indicated that acid-sensing ion channels (ASICs) may play an important role in suppressing status epilepticus (SE) in rats, the precise mechanism is unclear. We attempted to investigate the antiepileptic effect of amiloride in SE rats and its mechanism. METHODS: Rats with seizures induced by Li-pilocarpine were randomly divided into four groups, phosphate buffer saline (PBS) group, amiloride group, levetiracetam group and acidic liquid group, respectively. The electroencephalogram (EEG) of each group was recorded. Then rats treated with different drugs (2 h after amiloride or PBS injection or 1 h after PBS injection) and a normal control group was selected for reverse transcription-polymerase chain reaction (RT-PCR). The expression of ASIC1a, ASIC3 and sodium-hydrogen exchanger (NHE) in each group was detected. RESULTS: Amiloride reduced the frequency of discharge in 60~90 min after injection significantly. In acidic liquid group, the epileptic discharge was increased in 0~30 min. Moreover, the expression of ASIC1a, ASIC3 and NHE was obviously increased in the SE groups. Compared with SE groups, the expression of ASIC1a and ASIC3 mRNA in amiloride group decreased significantly. While NHE mRNA expression in the SE groups showed no significant difference. CONCLUSION: Amiloride inhibited pilocarpine-induced SE and the anti-epileptic mechanism was associated with deactivation of the ASIC1a and ASIC3 instead of NHE in rats. PMID- 26823771 TI - Role of MICA expression, anti-MICA antibodies and serum MICA during acute rejection in a rat-to-mouse cardiac transplantation model. AB - BACKGROUND AND OBJECTIVE: Human major histocompatibility complex class I-related gene A (MICA) is reportedly associated with poor transplant outcomes and a high risk of acute and chronic rejection in solid organ transplantation. However, studies on these risks have found conflicting results. In the present study, we investigate the MICA expression and serum MICA (sMICA) as well as the MICA antibodies (anti-MICA) in serum of recipients during acute rejection (AR) in a rat-to-mouse cardiac transplantation model. METHODS: Construct rat-to-mouse concordant cardiac transplantation models, histological examination of the heart in recipients during AR at 2-6 hours time point was done. We then studied the MICA gene expression of the heart in recipients during AR at 2-6 hours time point by western blot and RT-PCR assay. We latter studied the anti-MICA and sMICA levels in serum of recipients during AR at 2-6 hours time point by Flow cytometry and ELISA measurement. RESULTS: We found that Lewis rat hearts transplanted into BALB/c mice developed typical AR in 6 days. The level of severity of xenograft rejection from 2 d to 6 d was increased in a time-dependant way. MICA protein and MICA mRNA was also increased in time-dependant way and reached the highest value at 6 h. The prevalence of anti-MICA was significantly higher among those with severe acute rejection. However, sMICA was significantly increased during AR at 2 hours, then gradually decreased, and reached the lowest value at 6 h. CONCLUSIONS: MICA expression in recipients' heart and anti-MICA antibodies in recipients' sera may associated with high risk of AR in rat-to-mouse transplantation. sMICA showed a negative association with acute rejection and may be a good predictor of heart transplant outcomes. PMID- 26823772 TI - MiR-145 suppressed human retinoblastoma cell proliferation and invasion by targeting ADAM19. AB - MicroRNAs (miRNAs) play critical roles in retinoblastoma (RB) initiation and progression, aberrant expression of miR-145 had been frequently reported in cancer studies. However, the role and mechanism of its function in RB is still unclear. In this study, our data showed that miR-145 was downregulated in RB tissues and cell lines. Overexpression of miR-145 suppressed RB cell proliferation, migration and invasion in vitro. ADAM19 was identified as a direct target of miR-145. Silencing of ADAM19 significantly inhibited RB cell proliferation, migration and invasion. In addition, a reverse correlation between miR-145 and ADAM19 expression was noted in RB tissues. Taken together, these findings suggested that miR-145 functions as a tumor suppressor in RB by directly targeting ADAM19. miR-145 could be an anticancer therapeutic target for RB patients. PMID- 26823773 TI - Effect of bone mesenchymal stem cells transplantation on the micro-environment of early osteonecrosis of the femoral head. AB - Autologous implantation of bone mesenchymal stem cells (BMSCs) has achieved promising clinical efficacy for the treatment of early-stage osteonecrosis of the femoral head (ONFH). However, the underlying mechanisms are not completely elucidated. Here, we investigated the effect of BMSCs on the early ONFH in vitro and in vivo. In co-cultured system, primary BMSCs enhanced the activity and inhibited the apoptosis of primary OB. The concentrations of VEGF and BMP-2 in the co-cultured medium were significantly higher than those without co-culture. Importantly, BMSCs implantation increased OB, capillaries and VEGF and BMP-2 expressions of the necrotic areas of femoral head in the ONFH rabbits. In conclusion, our results indicated that BMSCs treated the early ONFH possibly through increasing OB and capillaries, as well as VEGF and BMP-2 expression in the femoral head. These results provided possible mechanisms for the treatment of early-stage ONFH with BMSCs transplantation. PMID- 26823774 TI - KIR2DL4 expression rather than its single nucleotide polymorphisms correlates with pre-eclampsia. AB - OBJECTIVE: To evaluate the single nucleotide polymorphisms and expression of KIR2DL4 (killer cell immunoglobulin-like receptors) gene in pre-eclampsia patients. METHODS: KIR2DL4 gene polymorphisms were detected in 100 patients with pre-eclampsia and 100 healthy pregnant women, respectively, by using PCR-SS. Then, the expression of KIR2DL4 was measured in 5 cases of placentas tissues with pre-eclampsia and normal pregnancies by using qRT-PCR. RESULTS: Compared with healthy controls, 16 loci of single nucleotide polymorphisms (SNP) were identified in pre-eclampsia patients, including 7 new polymorphisms loci. But, no significant difference was found in genotype distributions and allele frequencies in pre-eclampsia and controls (P>0.05). However, qRT-PCR results showed that KIR2DL4 mRNA in placenta tissues with pre-eclampsia was significantly lower than those with normal pregnancy, and the difference was statistically significant. CONCLUSION: Decreased level of KIR2DL4 rather than its SNP is correlated with the susceptibility of pre-eclampsia. PMID- 26823775 TI - Effect of CXCL10 receptor antagonist on islet cell apoptosis in a type I diabetes rat model. AB - In recent years, the incidence of type 1 diabetes mellitus (T1DM) has been increasing. The role of CXCL10 and its receptor, CXCR3, in the occurrence of T1DM has drawn lots of research interests, as the disease incidence was correlated with their expression levels. We thus used an antagonist of CXCR3, NBI-74330, to block the specific binding, for further observation of islet cell apoptosis in a T1MD rat model. A total of 80 SD rats were given STZ intraperitoneally for generating T1DM model. Different concentrations of NBI-74330 were then applied, followed by the collection of blood and pancreatic tissue samples. CXCL10 and CXCR3 levels were detected by enzyme linked immunosorbent assay (ELISA), followed by expressional assays in pancreatic tissues by real-time PCR, Western blotting and flow cytometry. Compared to control group, model rats had significantly elevated blood glucose level (>16.7 mmol/L), with depressed CXCL10 and CXCR3 levels compared to model group (P<0.05). After NBI-74330 treatment, mRNA and protein levels of CXCL10 and CXCR3 were significantly lowered, with significantly decreased apoptotic cell ratios compared to model group (P<0.05). CXCL10 receptor antagonist NBI-74330 can inhibit the apoptosis of pancreatic islet cells in T1DM rats. PMID- 26823776 TI - PRAME induces apoptosis and inhibits proliferation of leukemic cells in vitro and in vivo. AB - PRAME is a germinal tissue-specific gene that is expressed at high levels in haematological malignancies, but the physiological functions of PRAME in leukemia cells are unknown. It has reported that PRAME was found to be predominantly expressed in acute leukemias and high PRAME expression is correlated with a favorable prognosis in childhood acute leukemias, which suggested that PRAME could be involved in the regulation of cell death or apoptosis. In the present study, we tested a hypothesis that the PRAME gene plays a role in the regulation of apoptosis and proliferation of leukemia cells. We observed that KG-1 cells transient overexpressing the PRAME gene (when transfected with pcDNA3.1-PRAME plasmid) significantly induces apoptosis and decreases proliferation in vitro, and repression of PRAME expression by a short interfering RNA exhibited a increased proliferation in K562 cells in vitro and increases tumorigenicity of K562 leukemic cells in nude mice. Our results suggest that the leukemias expressing high levels of PRAME has favorable prognosis. PRAME may be as an attractive target for potential immunotherapy for acute leukemic. PMID- 26823777 TI - Expression of MMP-9/TIMP-2 in nasal polyps and its functional implications. AB - Nasal polyps (NP) involve tissue repair and structural remodel, both of which require the extracellular matrix. Matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) are known regulators for tissue reconstruction. This study therefore aimed to analyze the expressional profile of MMP-9 and TIMP-2 in NP patients, with further investigation of their roles in pathogenesis. A total of 60 NP tissue samples (including 15 type I, 21 type II and 24 type III) were collected from surgeries in our hospital, in addition to 6 normal ethmoid sinus mucosa samples. The mRNA and protein expression levels of MMP-9/TIMP-2 were quantified by real-time PCR and Western blotting, respectively. Serum levels were also checked by enzyme-linked immunosorbent assay (ELISA). Both mRNA and protein levels of MMP-9 in NP tissues or serum were significantly elevated compared to those in control ones (P<0.05) while the TIMP-2 expression was suppressed (P<0.05). In patients with more advanced stage, MMP-9 expression was further elevated, with lowered TIMP-2 levels (P<0.05 in both cases). Pathogenesis and progression of NP is closely related with elevated MMP-9 and suppressed TIMP-2 expression, suggesting the role of those factors as indexes for evaluating NP stage. Our results also provide evidences for further studies of pathogenesis and drug targets of NP. PMID- 26823778 TI - MiR-451 inhibits synovial fibroblasts proliferation and inflammatory cytokines secretion in rheumatoid arthritis through mediating p38MAPK signaling pathway. AB - Rheumatoid arthritis is an autoimmune disease characterized as joint synovial inflammation. MicroRNA is a group of small noncoding RNA molecules discovered in recent years that can posttranscriptional regulate mRNA expression and involved in a variety processes of immune cell activation and differentiation. There is still lack of study about the role of miR-451 in rheumatoid arthritis. Synovial fibroblasts isolated from rheumatoid arthritis patients were cultured in vitro. Chemical synthesized miR-451 was lipo-transfected, real-time RT-PCR was applied to detect miR-451 expression level, and MTT method was used to detect the effect of miR-451 on synovial fibroblasts proliferation. Enzyme-linked immunosorbent assay was used to detect tumor necrosis factor TNF-alpha, IL-1beta, and IL-6 level in the supernatant. Western blot was applied to test target protein p38 MAPK expression level. Our study found that synovial fibroblasts expressed higher miR-451 mRNA level in miR-451 treatment group. MiR-451 treatment significantly decreased cell proliferation ability (P < 0.05). Compared with the control, p38 MAPK protein expression reduced obviously in the miR-451 treatment group (P < 0.05). MiR-451 transfected synovial fibroblasts secreted lower levels of TNF alpha (198 +/- 12 pg/ml vs 124 +/- 13 pg/ml, P < 0.01), IL-1beta (352 +/- 43 pg/ml vs 165 +/- 87 pg/ml, P < 0.01), and IL-6 (487 +/- 84 pg/ml vs 257 +/- 92 pg/ml, P < 0.01). The results proved that miR-451 can down-regulate p38 MAPK protein expression, and reduce synovial fibroblasts proliferation and cytokine expression level. PMID- 26823779 TI - TFF3 knockout in human pituitary adenoma cell HP75 facilitates cell apoptosis via mitochondrial pathway. AB - Trefoil factor 3 (TFF3), a regulatory protein composed of 59 amino acids, has been suggested to be involved in pathogenesis, proliferation, differentiation, invasion, migration and apoptosis in multiple malignant tumors. This study thus investigated the effect of TFF3 knockout in human pituitary adenoma cell line HP75 on cell apoptosis and related pathways. RNA interference approach was used to knock down the expression of TFF3 protein. The gene silencing was validated by RNA denaturing gel electrophoresis and Western blotting. The effect of TFF3 knockout on cell apoptosis was analyzed by Western blotting and flow cytometry. TFF3 protein level in pituitary adenoma was about 3.61 +/- 0.48 folds of that in normal tissues (P < 0.01). After transfecting with small interference RNA (siRNA) against TFF3, the apoptotic ration was significantly elevated (P < 0.01). Apoptosis related protein Bcl-2 and caspase-3 levels were remarkably depressed after siRNA transfection, while Bax and cleaved caspase-3 levels were elevated. TFF3 protein knockout can facilitate apoptosis of human pituitary adenoma HP75 cells via mitochondrial pathway. PMID- 26823781 TI - A giant ureteral polyp mimicking as a bladder mass resected ureteroscopically by diode laser: a case report and literature review. AB - We presented a rare case with giant ureteral polyp that mimics bladder tumor in adult women, originating from the middle segment of the left ureter. The patient was a 42-year-old woman, with a 2.1*1.3 cm bladder mass detected incidentally on a health screening ultrasound. Computerized tomography (CT) of the pelvis revealed a solid tumor situated near to trigon. Cystoscopy demonstrated a tumor that periodically prolapsed into the bladder. After the tumor was identified as a ureteral polyp by ureteroscopy, an ureteroscopic resection by diode laser was performed. The tumor measured 9.0*0.5 cm, and the final pathological diagnosis was ureteral fibroepithelial polyp. No recurrence was observed at the 5-month follow-up. PMID- 26823780 TI - Suppression of hedgehog signaling regulates hepatic stellate cell activation and collagen secretion. AB - Hepatic stellate cells (HSCs) play an important role in liver fibrosis. This study investigates the expression of hedgehog in HSC and the role of hedgehog signaling on activation and collagen secretion of HSC. Liver ex vivo perfusion with collagenase IV and density gradient centrifugation were used to isolate HSC. Expression of hedgehog signaling components Ihh, Smo, Ptc, Gli2 and Gli3 in HSC were detected by RT-PCR. Hedgehog siRNA vectors targeting Ihh, Smo and Gli2 were constructed and transfected into HSC respectively. Suppression of hedgehog signaling were detected by SYBR Green fluorescence quantitative RT-PCR. Effects of hedgehog signaling inhibition on HSC activation and collagen I secretion were analyzed. Hedgehog signaling components Ihh, Smo, Ptc, Gli2 and Gli3 were expressed in HSC. siRNA vectors targeting Ihh, Smo and Gli2 were successfully constructed and decreased target gene expression. Suppression of hedgehog signaling significantly decreased the expression of alpha-SMA in HSC (P<0.01). Collagen type I secretion of HSC were also significantly decreased (P<0.01). In summary, HSC activation and collagen secretion can be regulated by hedgehog signaling. Hedgehog may play a role in the pathogenesis of liver fibrosis. PMID- 26823782 TI - Effects of donors' age and passage number on the biological characteristics of menstrual blood-derived stem cells. AB - We investigated the effects of donor age and passage number on the biological characteristics of menstrual blood-derived stem cells (MenSCs) by comparing MenSCs derived from donors with three different age ranges and after different passage times. Continuous passage, flat cloning, cell proliferation assays, flow cytometric phenotyping and whole human genome microarray were performed to systematically analyze the relationship between the self-renewal ability of MenSCs as well as their potential to maintain their stem cell characteristics and to resist aging. The results demonstrated that the immunophenotypes and in vitro cultural characteristics of MenSCs did not change significantly with the progression of aging. However, some important signal pathways including MAPK, the insulin signaling pathway, pathways involved in carcinogenesis such as PPAR and P53, and cytokines and their receptors, as well as other pathways associated with immune response and aging, changed to various extents under the conditions of aging after a long time in vitro. The enriched differentially-expressed genes were mainly involved in transcriptional regulation, stress response, cell proliferation, development and apoptosis. The key differentially-expressed genes associated with age and passage number were identified for use as biomarkers of cell aging. PMID- 26823783 TI - Co-culture with periodontal ligament stem cells enhanced osteoblastic differentiation of MC3T3-E1 cells and osteoclastic differentiation of RAW264.7 cells. AB - OBJECTIVES: Periodontal ligament stem cells (PDLSCs) are characterized by having multipotential differentiation and immunoregulatory properties, which are the main mechanisms of PDLSCs-mediated periodontal regeneration. Periodontal or bone regeneration requires coordination of osteoblast and osteoclast, however, very little is known about the interactions between PDLSCs and osteoblast-like cells or osteoclast precursors. In this study, the indirect co-culture approach was introduced to preliminarily elucidate the effects of PDLSCs on differentiation of osteoblast-like cells and osteoclast precursors in vitro. MATERIALS AND METHODS: Human PDLSCs were obtained from premolars extracted and their stemness was identified in terms of their colony-forming ability, proliferative capacity, cell surface epitopes and multi-lineage differentiation potentials. A noncontact co culture system of PDLSCs and preosteoblastic cell line MC3T3-E1 or osteoclast precursor cell line RAW264.7 was established, and osteoblastic differentiation of MC3T3-E1 and osteoclastic differentiation of RAW264.7 were evaluated. RESULTS: PDLSCs exhibited features of mesenchymal stem cells. Further investigation through indirect co-culture system showed that PDLSCs enhanced ALP activity, expressions of ALP, Runx2, BSP, OPN mRNA and BSP, OPN proteins and mineralization matrix deposition in MC3T3-E1. Meanwhile, they improved maturation of osteoclasts and expressions of TRAP, CSTK, TRAF6 mRNA and TRAP, TRAF6 proteins in RAW264.7. CONCLUSIONS: PDLSCs stimulates osteoblastic differentiation of osteoblast precursors and osteoclastic differentiation of osteoclast precursors, at least partially, in a paracrine fasion. PMID- 26823784 TI - Expression of tumoral FOXP3 in gastric adenocarcinoma is associated with favorable clinicopathological variables and related with Hippo pathway. AB - FOXP3 is a transcription factor and well-known hallmark of immune suppressive T regulatory cells (Tregs). Recent studies indicate that, in addition to its association with Treg function in the immune system, FOXP3 plays an important role in tumor development. And important tumor suppressor relay between the FOXP3 and Hippo pathways was found in human cancer. Thus, we investigated tumoral FOXP3, infiltrated Tregs count, Lats2, and YAP expression in gastric adenocarcinoma, and the relationships between expression of these three proteins and p53, Ki67, and other clinicopathological variables. We used 118 gastric adenocarcinoma tissues via immunohistochemical analysis, using a tissue microarray, in relation to survival and other clinicopathological factors. We report the several novel observations about the relationship between tumoral FOXP3 and Hippo pathway components in gastric adenocarcinoma. Positive tumoral FOXP3 expression was significantly related with smaller tumor size, tubular tumor type, lower histological grade, lower T stage, lower recurrence rate, less lymphatic invasion, and less neural invasion. Furthermore, patients with positive tumoral FOXP3 experienced significantly better disease-free and overall survival compared to patients with negative tumoral FOXP3. These findings show that tumoral FOXP3 expression is associated with favorable clinicopathological variables in gastric adenocarcinoma. And we report the novel observation of a relationship between tumoral FOXP3 and Hippo pathway components in gastric adenocarcinoma. Tumoral FOXP3 expression, infiltrated Tregs count, and Lats2 expression were all positively correlated with YAP expression. These findings suggest that the Hippo pathway in gastric adenocarcinoma might be influenced by both tumoral FOXP3 and infiltrated Tregs. In conclusion, the loss of FOXP3 expression in cancer cells is thought to contribute to tumorigenesis and progression of gastric adenocarcinoma. The expression of FOXP3 in gastric adenocarcinoma is related with Lats2 and YAP expression of the Hippo pathway. PMID- 26823785 TI - Expression of CDKN1A/p21 and TGFBR2 in breast cancer and their prognostic significance. AB - BACKGROUND: A new diagnostic and prognostic biomarker may be of value in cancer diseases. Our study aimed to evaluate the CDKN1A/p21 and TGFBR2 level measurable in a cohort of patients with breast cancer after mastectomy, and to confirm their suitability to serve as prognostic biomarkers of the cancer. METHODS: The expression levels of CDKN1A/p21 and TGFBR2 were detected by reverse transcription PCR (RT-PCR), western blot assay and immunohistochemical staining for 65 primary tumor samples and paired adjacent noncancerous breast tissues. Their relations to clinicopathologic parameters and to the prognosis of patients with breast cancer were analyzed. RESULTS: We found the mRNA and protein expression levels of CDKN1A/p21 were significantly upregulated in breast cancer tissues compared with adjacent nontumorous breast tissues. Increased CDKN1A/p21 expression showed a significant correlation with larger tumor size (P=0.014), higher tumor dedifferentiation grade (P=0.021), lymph node metastasis (P=0.019) and a shorter disease-free survival (P=0.044). Contrarily, the expression levels of TGFBR2 mRNA and protein were significantly decreased in breast cancer tissues compared with adjacent nontumorous breast tissues. Underexpression of TGFBR2 in breast cancer was correlated with larger tumor size (P=0.034), lymph node metastasis (P=0.039) and a shorter disease-free survival (P=0.035). Statistical analysis suggested that there was no significant association between CDKN1A/p21 and TGFBR2 expression. CONCLUSIONS: in summary, our results suggested that high CDKN1A/p21 and low TGFBR2 expression was closely correlated with adverse pathological parameters and poor prognosis in breast cancer. Both CDKN1A/p21 and TGFBR2 are presented as possible candidates for breast cancer biomarkers. PMID- 26823786 TI - Smooth muscle immaturity in the carotid arterial neointima as a prognostic marker for systemic atherogenic cardiovascular events in the Asian male. AB - Although immaturity of neointimal smooth muscle cells (SMCs) in coronary arteries has recently been demonstrated to be associated with acute coronary syndrome, the carotid arterial counterpart has not been investigated. We hypothesized that the same investigation of carotid endarterectomy specimens might contribute to living patients. Carotid endarterectomy specimens from 33 Asian males who underwent a 5 year follow-up were examined. Age, atherosclerotic risk factors, and percentage stenosis were investigated. Histologically, the fibrous cap/lipid core ratio was measured. Maturation of SMCs was assessed by the h-caldesmon/smooth muscle actin (SMA) ratio by immunohistochemistry in 3 different regions (luminal, medial, and opposite side of lipid core) in the neointima. Associations of these factors with preoperative symptoms along with postoperative systemic atherogenic cardiovascular events were analyzed. It was revealed that fibrous cap/lipid core ratio was significantly lower in symptomatic than in asymptomatic patients, while the h-caldesmon/SMA ratio was significantly lower in patients with than without postoperative systemic atherogenic cardiovascular events by the Student's t-test (P<0.05). Logistic regression model demonstrated that younger age and a lower h caldesmon/SMA ratio were associated with postoperative systemic atherogenic cardiovascular events (P<0.05). This result was not different when 3 different regions were each analyzed instead. Immaturity of neointimal SMCs shown by a lower h-caldesmon/SMA ratio by immunohistochemistry was associated with systemic atherogenic cardiovascular events. Thus, this finding may be predictive of these events after carotid endarterectomy. Uniform results among different neointimal regions suggest that immaturity of neointimal SMCs causes plaque instability and does not occur secondarily to plaque instability. PMID- 26823787 TI - Nuclear translocation of fibroblast growth factor receptor 3 and its significance in pancreatic cancer. AB - Nuclear translocation of fibroblast growth factor receptor 3 (FGFR3) was previously observed in some kinds of cancer. However, whether the phenomenon occurs in pancreatic cancer (PC), a malignancy with very dismal prognosis, remains unknown. In the present study, FGFR3 expression was firstly detected by Western blot and immunohistochemical staining in specimens of PC. Then, its correlations with clinicopathologic features and patient survival were evaluated. It was shown that FGFR3 was highly expressed in all the nuclear extracts, but in only one out of four whole tissue lysates, of tumor tissues, in contrast to those of non-tumor ones. Using immunohistochemistry, nuclear expression of FGFR3 was found to mainly locate in tumor cells, and was significantly associated with N stage. Furthermore, high FGFR3 nuclear expression was revealed to be associated with poor overall and disease-free survival in univariate analysis. For overall survival in the whole cohort and disease-free survival in patients with curative resection, high nuclear expression of FGFR3 was significant or marginally significant in multivariate analysis. However, its cytoplasmic expression was not related to clinical, pathologic variables and prognosis. These data suggest that nuclear translocation of FGFR3 is frequent and carries clinicopathologic as well as prognostic significances in PC. PMID- 26823788 TI - Morphoquantitative analysis of the Ileum of C57BL/6 mice (Mus musculus) fed with a high-fat diet. AB - Due to the increase in overweight and obesity in humans, various studies have been conducted in recent years that demonstrate the detrimental effects on tissues and organs. The aim of this study was to assess the morphoquantitative changes produced in the ileum of mice, associated with high-fat diets. Fourteen male C57BL/6 mice, 5 months old, were fed two types of diets for 14 weeks. The control group (C) was fed a standard diet (10% fat, AIN-93M) and the experimental group (E) was fed a high-fat diet (42% fat, AIN-93M-AG). The assessments included: body weight, calorie consumption, food efficiency, biochemical analysis of plasma lipids, diameter, total wall thickness, thickness of the tunica mucosa and tunica muscularis, length and width of the intestinal villi, depth of the intestinal crypts and number of goblet cells per mm(-2) (NA). For the statistical analysis the Student's t-test was used, considering a P value less than 0.05. The mice in the E group presented greater weight gain (P = 0.028), higher levels of total and LDL cholesterol (P = 0.03 and P = 0.01, respectively), and length of the intestinal villi (P = 0.000). The width of the intestinal villi and the NA of PAS-positive goblet cells presented significantly lower values (P = 0.037 and P = 0.039, respectively) than the C group. The observed changes could be related to the higher demand for fat absorption and to possible alterations in the intestinal microflora and inflammation by action of high-fat diets. PMID- 26823789 TI - Serum MicroRNA-370 as a potential diagnostic and prognostic biomarker for pediatric acute myeloid leukemia. AB - BACKGROUND: Controversial data on the expression pattern of microRNA-370 (miR 370) in acute myeloid leukemia (AML) were previously reported. OBJECTIVE: To clarify the expression pattern of miR-370 and its clinical implications in pediatric AML patients. METHODS: Real-time quantitative PCR was performed to detect the expression of miR-370 in both bone marrow mononuclear cells and sera obtained from pediatric AML patients and healthy controls. RESULTS: Compared with healthy controls, the expression levels of miR-370 in the bone marrow and sera of pediatric AML patients were both decreased significantly (both P=0.001). Importantly, serum miR-370 level could efficiently screen pediatric AML patients from healthy controls (Area under receiver operating characteristic curve, AUC =0.993). Then, low serum miR-370 level was significantly associated with French American-British (FAB) classification subtype M7 subtype (P=0.02) and unfavorable karyotype (P=0.01). Moreover, pediatric AML patients with low serum miR-370 level had shorter relapse-free and overall survivals than those with high serum miR-370 level (both P=0.001). Multivariate analysis further identified serum miR-370 level as an independent prognostic factor for both relapse-free and overall survivals. Interestingly, the prognostic relevance of serum miR-370 level was more obvious in the subgroup of patients with intermediate-risk cytogenetics. CONCLUSIONS: MiR-370 expression may be markedly and consistently decreased in pediatric AML patients and in turn contributes to aggressive progression of this malignancy. Serum miR-370 may serve as a potential non-invasive diagnostic/prognostic marker for pediatric AML patients. PMID- 26823790 TI - Differential loss of natural killer cell activity in patients with acute myocardial infarction and stable angina pectoris. AB - BACKGROUND: To evaluate the activity of natural killer cells through their inhibitory and activating receptors and quantity in peripheral blood mononuclear cells extracted from patients with acute myocardial infarction, stable angina pectoris and the controls. METHODS: 100 patients with myocardial infarction, 100 with stable angina, and 20 healthy volunteers were recruited into the study. 20 randomly chosen people per group were examined for the whole human genome microarray analysis to detect the gene expressions of all 40 inhibitory and activating natural killer cell receptors. Flow cytometry analysis was applied to all 200 patients to measure the quantity of natural killer cells. RESULTS: In myocardial infarction group, the mRNA expressions of six inhibitory receptors KIR2DL2, KIR3DL3, CD94, NKG2A, KLRB1, KLRG1, and eight activating receptors KIR2DS3, KIR2DS5, NKp30, NTB-A, CRACC, CD2, CD7 and CD96 were significantly down regulated (P<0.05) compared with both angina patients and the controls. There was no statistical difference in receptor expressions between angina patients and control group. The quantity of natural killer cells was significantly decreased in both infarction and angina patients compared with normal range (P<0.001). CONCLUSIONS: The significant mRNAs down-regulation of several receptors in myocardial infarction group and reduction in the quantity of natural killer cells in both myocardial infarction and angina patients showed a quantitative loss and dysfunction of natural killer cells in myocardial infarction patients. PMID- 26823791 TI - Expression of molecular factors correlated with metastasis in small cell lung cancer and their significance. AB - Distant metastasis continues to be a fatal threat to quality of life in patients with small cell lung caner (SCLC). The purpose of this work is to analyze the expressions of chemokine receptor four (CXCR4), matrix metalloproteinase-9 (MMP 9), transforming growth factor-b1 (TGF-beta1), N-cadherin and vascular endothelial growth factor (VEGF) in small cell lung caner (SCLC), and to explore their correlations with the prognosis and metastasis. Sixty-five consecutive patients with stage I-III SCLC who received operation in our hospital from Jan 2003 to Oct 2009 were retrospectively analyzed. The expression of CXCR4 was found significantly correlated with bone metastasis (P = 0.004), and were marginally correlated with brain metastasis (P = 0.068) and lymph node metastasis (P = 0.085). The expression of MMP-9 was significantly associated with pathological staging (P = 0.048). Univariate analysis suggested surgical approach, clinical stage, lymph node metastasis were significantly associated with OS and PFS (P < 0.05), high expression of CXCR4 was significantly correlated with worse OS (P = 0.004) and PFS (P = 0.005). Multivariate analysis suggested surgical approach, TGF-beta1, CXCR4 and lymph node metastasis were independent prognostic factor for PFS. In conclusion, High expression of CXCR4, MMP-9, TGF-beta1 and VEGF were found in SCLC. High expression of MMP-9 was significantly associated with pathological staging, and high expression of CXCR4 was correlated with bone metastasis and also might correlate with brain metastasis. CXCR4 were independent prognostic factor for survival in SCLC and expanded samples should be further explored in the future. PMID- 26823792 TI - CYP2E1 RsaI/PstI polymorphisms contributed to oral cancer susceptibility: a meta analysis. AB - Several studies have investigated the associations between CYP2E1 RsaI/PstI polymorphisms and oral cancer risk, but results have been inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. PubMed and China National Knowledge Infrastructure (CNKI) searches were carried out for relevant studies published before September 2014. Meta analysis was performed with the Stata, version 11.0. A total of 14 case control studies, including 1,962 cases and 3,271 controls, were selected. Overall, significant association was found between the CYP2E1 RsaI/PstI polymorphisms and oral cancer risk (for c1c1 vs. c1c2, OR=0.72, 95% CI=0.56-0.91; for c1c1 vs. c2c2, OR=0.45, 95% CI=0.25-0.82), while not for the dominant model (c1c1 vs. c1c2+c2c2, OR=0.84, 95% CI=0.69-1.01). In the subgroup analysis by ethnicity, statistically significant association was found in Caucasian, East Asian and South Asian. This meta-analysis suggests that the CYP2E1 RsaI/PstI polymorphisms are a risk factor for developing oral cancer. PMID- 26823793 TI - Pemetrexed and cyclophosphamide combination therapy for the treatment of non small cell lung cancer. AB - Lung cancer is the leading cause of cancer-related mortality. This study was undertaken to investigate the efficacy and safety of adding regulatory T cell inhibitor cyclophosphamide to pemetrexed therapy for the second-line treatment of NSCLC with wild-type epidermal growth factor receptor (EGFR). A total of 70 patients were screened between March 2011 and December 2013, out of which 62 patients were enrolled in the study. Patients were randomized to receive 500 mg/m(2) pemetrexed in combination with 20 mg/kg cyclophosphamide in a 21 day cycle (n=30) or 500 mg/m(2) pemetrexed (n=32), and followed up for 30 months. Disease progression was observed in 23 patients in the pemetrexed plus cyclophosphamide arm and 27 patients in the pemetrexed monotherapy arm. Median progression-free survival was 3.6 months (95% confidence interval [CI], 1.3 to 5.9 months) in the pemetrexed plus cyclophosphamide arm and 2.2 months (95% CI, 1.3 to 3.1 months) in the pemetrexed monotherapy arm. The 6-month PFS rates were 22% (95% CI, 10 to 34) and 14.5% (95% CI, 6 to 23) in the pemetrexed plus cyclophosphamide arm and pemetrexed monotherapy arm, respectively. Median overall survival was 9.8 months for the pemetrexed combination therapy arm and 8.8 months for the pemetrexed arm, and the 1-year survival rates were 46% and 33%, respectively. The present study showed that pemetrexed in combination with low dose cyclophosphamide may be a better treatment approach than pemetrexed monotherapy when considering second-line treatment for wild-type EGFR NSCLC. PMID- 26823794 TI - Bax inhibiting peptide reduces apoptosis in neonatal rat hypoxic-ischemic brain damage. AB - Neonatal hypoxic ischemic encephalopathy (HIE) has been reported to induce apoptosis in neonates. We, therefore, analyzed the ability of Bax-inhibiting peptide (BIP) to provide neuroprotective effects during hypoxic-ischemic brain damage (HIBD). Seven-day-old wistar rat pups (n = 198) were randomly divided into a sham-operated group (Group S, n = 18), saline group (Group C, n = 90) and BIP group (Group B, n = 90). Pathological changes in the cerebral tissues of rat pups were analyzed using hematoxylin and eosin stain, TUNEL and Western blot. The expression of cytochrome c and caspase-3 was determined using western blot technique. Rat pups demonstrated neurobehavioral alteration in Groups C and B. TUNEL-positive cells in the left hippocampus were significantly increased in Group C and Group B after HIBD (P < 0.01) when compared with Group S. There was a marked reduction in TUNEL positive cells in subgroups B1 through B4 when compared with the respective subgroups C1 through C5. Compared with Group S, the expression of caspase-3 and cytochrome c was significantly increased in Groups C and B (P < 0.01). The difference in expression of caspase-3 and cytochrome c between subgroups B1 through B4 and C1 through C4 was significant (P < 0.01). In conclusions, the neuro-protective effect of BIP was due to a reduction of nerve cell apoptosis in our neonatal HIE rat model. We propose that BIP has potential as a neuro-protective drug in neonatal HIE cases. PMID- 26823795 TI - Diagnostic utility of PAX2 and PAX5 in distinguishing non-small cell lung cancer from small cell lung cancer. AB - Lung cancer is the leading cause of cancer-related death in both men and women and consists of different histological types. Histopathological examination and accurate subtype diagnosis has become increasingly important in guiding patient management and, as such, is the most important currently available lung cancer "biomarker". In this study, we examined the expression of PAX2 and PAX5 by immunohistochemistry in 47 cases of lung cancer and 13 cases of pneumonia. The results demonstrated that PAX2 were detected in 82.8% (24/29) of NSCLC, 0% (0/18) of SCLC and 7.7% (1/13) of pneumonia, respectively; However, PAX5 were detected in 15/18 cases (83.3%) of SCLC, 6.8% (2/29) of NSCLC and 7.7% (1/13) of pneumonia. Further, the samples with lymphatic metastasis had remarkable higher positive PAX2 or PAX5 than that without metastases. Overall, our data indicated that PAX2 and PAX5 differentially expressed in NSCLC and SCLC. Thus, PAX2 and PAX5 are useful biomarker in the differential diagnosis of lung cancer. PMID- 26823796 TI - Impacts of Rho kinase inhibitor Fasudil on Rho/ROCK signaling pathway in rabbits with optic nerve injury. AB - OBJECTIVE: The aim of this study was to study the impacts of Rho kinase inhibitor Fasudil on expressions of Rho/ROCK signaling pathway associated genes in rabbits with optic nerve injury (ONI), and to explore the therapeutic mechanisms towards ONI. METHODS: The rabbit ONI model was established, then the rabbits were divided into model group (treated with saline), control group (treated with dexamethasone, Dex), and intervention group (treated with Fasudil, Fas). The eyeball and optic nerve were sampled at 3, 7, 14 and 21 days after injury. The morphological changes of retina and optic nerve were observed. The expressions of RhoA, Caspase-3, Rock 2 and Nogo-A gene were determined by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) methods. RESULTS: At different time after injury, there were significant differences of RhoA, Caspase-3, Rock 2 and Nogo-A gene expression among three groups (P < 0.05). CONCLUSIONS: After ONI, Fas can decrease the expression of Caspase-3 gene, and down-regulate the expressions of Nogo-A and Rock 2 gene. Therefore, it can treat ONI through affecting the Rho/ROCK signaling pathway. PMID- 26823797 TI - Impact of chemokine receptor CXCR3 on tumor-infiltrating lymphocyte recruitment associated with favorable prognosis in advanced gastric cancer. AB - Chemokine receptor CXCR3 has been proved to play an important role in tumorigenesis and tumor progression in many malignancies, but its precise efficacy on gastric cancer (GC) has not been evaluated yet. The present study was aimed to explore the correlation of chemokine receptor CXCR3 with tumor infiltrating lymphocytes (TILs) and prognosis in advanced gastric cancer (GC). Expression of CXCR3 and CD4+, CD8+ TILs was conducted in 192 advanced GC specimens and 48 corresponding paracancerous tissues by immunohistochemical (IHC) analysis. CXCR3 expression in GC tissues was significantly higher than that in paracancerous tissues (P<0.001) and CD8+, CD4+ TILs infiltration increased with high CXCR3 expression (P=0.032 and P<0.001, respectively). Our study showed significantly lower CXCR3 expression in patients with greater tumor invasion depth and lymph node metastasis compared with patients with lesser tumor invasion depth and without lymph node metastasis (P=0.002 and P=0.001, respectively). Univariate analysis indicated that patients with high CXCR3 expression and high CD8+ TILs infiltration had longer overall survival (OS) (log-rank test, P<0.001 and P=0.002, respectively). Univariate and multivariate analyses indicated that CXCR3 expression was an independent prognostic factor for OS (P=0.002). The present study suggested that CXCR3 expression was upregulated in advanced GC and was associated with increased CD4+, CD8+ TILs infiltration and improved OS. Therefore, CXCR3 overexpression is implicated as a favorable prognostic biomarker in human advanced GC. PMID- 26823798 TI - Endocan of the maternal placenta tissue is increased in pre-eclampsia. AB - PURPOSE: Pre-eclampsia (PE) is associated with intravascular inflammation and endothelial dysfunction. Interestingly, endocan plays a predominant role in the vascular inflammation and is considered as a biomarker of endothelial dysfunction. The aim of this study was to explore whether the endocan levels in serum and placenta were different between pregnant women with PE and the normal pregnancies. METHODS: Total 22 patients, including 10 normal pregnant women and 12 patients with PE, were included in this study. Immunohistochemistry was used to evaluate the location of endocan. Then, the mRNA and protein levels of endocan in placenta were detected using qRT-PCR and western blotting. Serum endocan concentration was measured by ELISA. RESULTS: Endocan protein was present in the human placenta, and the mRNA and protein levels of placenta tissues were elevated (P < 0.05) in the normal pregnancy with third trimester than those with first trimester. Furthermore, the expression of endocan mRNA and protein were increased in the placenta tissues of PE compared with in the normal pregnancy (P < 0.05); however, the endocan concentration of maternal serum did not have significant differences. CONCLUSION: Endocan may play a role in the progression of pregnancy and has a potential to be a new marker for the detective of PE. PMID- 26823799 TI - Low expression of PHLPP1 in sacral chordoma and its association with poor prognosis. AB - Sacral chordoma is a rare spine tumor with a high recurrence rate even after optimal therapy. Previous studies have demonstrated that the PI3K/AKT pathway plays a pivotal role in chordoma, and high expression of pAKT is associated with poor prognosis. Recently, PHLPP was recognized to be a tumor suppressor that targets AKT. We analyzed the expression of PHLPP1 and AKT2 in 37 chordoma samples and 11 fetal nucleus pulposus samples by immunohistochemical staining. Of the chordoma cases, 40.5% (15/37) showed strong cytoplasmic staining (score >=3) for PHLPP1, which was significantly lower than the 90.9% (10/11) of fetal nucleus pulposus samples (P = 0.004). Conversely, strong immunohistochemical staining for AKT2 was observed in 75.7% (28/37) of chordoma samples, which was significantly higher than 36.4% (4/11) of fetal nucleus pulposus (P = 0.021). Kaplan-Meier survival curves and log-rank test showed that patients with high expression of PHLPP1 experienced longer progression free survival time than those with low PHLPP1 expression (P = 0.011). Further multivariate Cox regression analysis indicated that PHLPP1 expression level and surgical approaches were independent risk factors for chordoma recurrence (P = 0.023 and P = 0.022). However, PHLPP1 expression was not statistically related to patients' total survival time. Conclusively, our results suggest that PHLPP1 plays a crucial role in sacral chordoma, and may be a promising biomarker for prognosis. Meanwhile, manipulation of PHLPP1 expression is also a potential therapeutic approach for the treatment of sacral chordoma. PMID- 26823800 TI - Association of apolipoprotein E with the progression of hepatitis B virus-related liver disease. AB - Hepatitis B virus (HBV) infection increases the risk of liver decompensation, cirrhosis and hepatocellular carcinoma (HCC). Apolipoprotein E (ApoE), one of the major cholesterol carriers, plays important role in the metabolism of lipoprotein and the regulation of immune response. The present study was aimed to explore whether the genetic variation in ApoE gene affected disease progression in HBV infected individuals. We collected sera samples from healthy volunteers (n=40), inactive HBV carriers (n=30), and patients with acute hepatitis (n=60), severe hepatitis (n=12), HBV-related liver cirrhosis (n=58) or primary HCC (n=39). We found that ApoE and interlukin-6 (IL-6) was progressively increased, while IL-2 was gradually decreased with the increasing grade of disease severity. Furthermore, high ApoE levels in HBV infected individuals were correlated with increased IL-6 and decreased IL-2 levels, indicating immune abnormalities in these patients. The frequency of E3/3 genotype was progressively increased from carriers group, hepatitis group to progressive group (cirrhosis and HCC). The serum levels of low-density lipoprotein cholesterol (LDL-C) differed among ApoE phenotypes, with E3/4, E4/4> E3/3>E2/3. Our study suggested that ApoE may have a role in the pathogenesis and progression of HBV-related liver disease and indicated the possible underlying mechanisms. PMID- 26823801 TI - Overexpression of CD39 and high tumoral CD39+/CD8+ ratio are associated with adverse prognosis in resectable gastric cancer. AB - CD39/ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1) is a cell surface located, rate-limiting enzyme in the generation of adenosine, and plays a crucial role in tumor development. We examined co-expression of CD39 and CD8in gastric cancer (GC) and showed that the expression of CD39 and CD8 increased significantly in tumor tissues compared to paired peritumor tissues. The expression of tumoral CD39 (tCD39), but not tumoral CD8 (tCD8), was related to overall survival. Furthermore, the CD39(+)/CD8(+) ratio was associated with poor prognosis in resected GC patients. Taken together, our data indicate that highCD39 expression and high tCD39(+)/CD8(+) ratio in GC is a predictor of poor prognosis for GC patients after radical resection. Moreover, CD39 could serve as a potential target for cancer immunotherapy. PMID- 26823802 TI - High expression of N-acetyltransferase 10: a novel independent prognostic marker of worse outcome in patients with hepatocellular carcinoma. AB - N-acetyltransferase 10 (NAT10) is a nucleolar protein involved in histone acetylation, telomerase activity regulation, DNA damage response and cytokinesis. The expression of NAT10 was found to be enhanced in several types of tumors, suggesting its correlation with tumor development. However, the specific role of NAT10 in hepatocellular carcinoma (HCC) is still unclear. The aim of this study was to investigate the expression of NAT10 in HCC patients and to assess the relationship of NAT10 expression with clinicopathological characteristics and tumor prognosis. We selected 17 pairs of HCC samples and adjacent non-neoplastic tissue for mRNA expression analysis. We also performed immunohistochemistry in 186 HCC samples to evaluate the NAT10 protein expression. Cox regression and Kaplan-Meier analysis was used to study the diagnostic and prognostic value of NAT10. The results showed that NAT10 expression was mainly localized in the nuclei/nucleoli and was significantly higher in HCC tissues than peritumoral tissues (P < 0.01). High NAT10 expression was positively correlated with histological differentiation (P < 0.01) and TNM classification (P < 0.01). Cox regression univariate and multivariable analysis revealed that expression of NAT10 in HCC was an independent prognostic factor for patient survival time. Our data suggested that NAT10 might be a promising prognostic marker and potential therapeutic target in HCC. PMID- 26823803 TI - Expression of esophageal carcinoma related gene 4 (ECRG4) and its clinical significance in prognosis of esophageal carcinoma. AB - This study aimed to analyze the relationship between the expression level of esophageal carcinoma related gene 4 (ECRG4) in esophageal cancer tissues and the occurrence of esophageal carcinoma. 50 cases of esophageal carcinoma tissues and adjacent tissues were collected as study samples. mRNA and protein expression levels of ECRG4 in tumor tissues and adjacent tissues were analyzed by real-time fluorescence quantitative PCR, Western blot and immunohistochemistry. The relationship between the expression level of ECRG4 and the clinical and pathological features and postoperative recurrence and survival was also analyzed. Real-time fluorescent quantitative PCR and Western blot showed that the mRNA and protein levels of ECRG4 in esophageal cancer tissues were significantly down regulated (P<0.04). There was ECRG low expression in 74 cases and high expression in 17 cases. The expression level of ECRG4 protein in esophageal carcinoma tissues was closely related to tumor invasion level, TNM staging and lymph node metastasis (P<0.05), but not related to gender, age, tumor type and differentiation degree of patients (P>0.05). The cumulative recurrence rate of patients of higher ECRG expression was significantly lower than that of patients of lower ECRG4 expression in 5 years after surgery, and the cumulative recurrence rate was 5 years (P<0.05). And the cumulative survival rate of patients with high ECRG4 expression was significantly higher than that of patients with low expression of ECRG4 in 5 years after surgery (P<0.05). In conclusion, the low expression or no expression of ECRG4 in esophageal cancer tissues was closely related to the degree of tumor invasion level, TNM staging, lymph node metastasis and recurrence and survival after surgery. PMID- 26823804 TI - Neutrophil-lymphocyte ratio: a controversial marker in predicting Crohn's disease severity. AB - Peripheral blood-derived inflammation-based scores such as the neutrophil lymphocyte ratio (NLR) have recently been proposed as prognostic markers in ulcerative colitis. In some previous serological markers are commonly used to detect the severity of the Crohn's disease (CD), but their sensitivity and specificity are relatively low. So we want to use simple indicators which are easy to obtain to predict disease severity. Now, we investigated and compared the capacity of NLR and other inflammatory markers in detecting CD activity and differentiating CD patients from healthy controls. These CD patients had not received corticosteroid or immunosuppressive drugs within a defined period of time. Data from our hospital between 2010 and 2012 was used. Neutrophil lymphocyte ratio (NLR), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cells (WBC), platelet count and albumin were measured in 44 patients with active CD, 66 patients with inactive CD, and 55 healthy blood donors. Disease activity was assessed by the Crohn's Disease Activity Index. In the active CD group, NLR values were found to be elevated compared to inactive CD patients and controls (6.00+/-7.38, 5.53+/-6.18 and 1.84+/-0.85, respectively), but statistical difference was not found between active and inactive CD groups. The overall accuracy of NLR (cutoff: 2.13 fl), CRP (cutoff: 10.5 mg/dl), ESR (cutoff: 19.5 mm/hour) and WBC (cutoff: 9.2 * 10(9)/l) in differentiating CD patients from healthy controls was 80.9%, 67.3%, 71% and 60% respectively. NLR values were found to be correlated with WBC and CRP levels. NLR increased in CD patients compared with healthy subjects. NLR had the best accuracy in determination of CD patients and healthy controls. NLR did not show a discriminative value in disease activity. PMID- 26823805 TI - Tubulocystic oncocytoma of the kidney: a case study and review of literature with focus on implications for differential diagnosis. AB - Renal oncocytoma (RO) can rarely present with a multilocular or tubulocystic growth pattern that may cause significant diagnostic difficulties with a variety of cystic renal cell carcinomas (RCC). Distinguishing these RO variants from their many RCC mimickers is critical because of its typical benign clinical course. Herein, we report a case of RO with extensive tubulocystic architectures on a 42-year-old female patient and discuss the clinicopathologic characterizations of this unusual RO variant with an emphasis on the wide spectrum of differential diagnoses of a variety of primary or secondary renal tumors that are featuring of both oncocytic cell changes and tubulocystic growth patterns. PMID- 26823806 TI - Matrine inhibited proliferation and increased apoptosis in human breast cancer MCF-7 cells via upregulation of Bax and downregulation of Bcl-2. AB - PURPOSE: The aim of the present study was to investigate the effects of matrine on proliferation and apoptosis in human breast cancer MCF-7 cells and its relevant molecular mechanisms. METHODS: Breast carcinoma cell line MCF-7 was cultured with series concentrations of Matrine in vitro. The proliferation and apoptosis of MCF-7 cells were investigated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT) assay, flow cytometry, and Mitochondrial membrane potential (MMP) measurements. The expression levels of Bax and Bcl-2 proteins were detected by Annexin V/propidium iodide coupled staining. The morphological changes of MCF-7 cell were examined. RESULTS: The inhibition rates of MCF-7 cells were 6.01%-37.01%, 7.56%-53.92%, and 10.86%-70.23% for 24, 48, and 72 hours after Matrine treatment, respectively. The proliferation of MCF-7 cells was significantly inhibited by Matrine administration, with a time and dose dependent manner. The rates apoptotic cells was between 4.17+/-0.25% and 19.63+/ 0.17% in 0.25-2.0 mg/ml Matrine groups, which had significant increased compare with the control groups (1.10+/-0.08%, P<0.05). Meanwhile, increased Bax expression, but decreased Bcl-2 expression was observed in MCF-7 cell line. MMP were significantly decreased by Matrine treatment. CONCLUSIONS: Matrine significantly inhibited the growth and induced apoptosis in breast carcinoma MCF 7 cells, which is related to Bax, Bcl-2 signaling and MMP. PMID- 26823807 TI - Fine needle aspiration biopsy of thyroid nodules: cytologic and histopathologic correlation of 1096 patients. AB - Via routinely used thyroid function tests, scintigraphy and ultrasonography (USG), important information is obtained in the clinical and diagnostic practice for thyroid nodules. However, the distinction between benign and malignant lesions cannot precisely be performed with these tests. Thyroid fine needle aspiration biopsy (FNAB) is considered the most reliable diagnostic method in the differentiation between benign and malignant thyroid nodules. It has recently been likely to perform aspiration from deeper nodules via the implemention of FNAB along with USG. Today, in cytopathological examination of thyroid FNAB, standardized Bethesda System for Reporting Thyroid Cytopathology (BSRTC) system is used. Here, FNAB was performed in 1096 patients with thyroid nodules in the Medical School of Selcuk University between January 2009 and July 2014. Patients consisted of 919 women and 177 men between 12 and 87 years of age. Evaluated via BSRTC, the results were classified as unsatisfactory, benign, atypia (or follicular lesions) of undetermined significance (AUS), follicular neoplasm or lesions suspicious for follicular neoplasm (FN), suspected malignant and malignant. After FNAB, 183 patients were operated and evaluated histopathologically. Histological malignancy rates of the categories were as follows: 16% (5), 15% (6) 14% (1) 60% (9), 72% (18) and 97% (63), respectively. In our study, we aimed to compare FNAB results of thyroid nodules with histopathology results after thyroidectomy and to show the sensitivity and specificity of FNAB technique to be higher in the follow-up and diagnosis of thyroid lesions. Given the malignancy detection rate in the follow-up of patients whose cytology was reported as inadequate, we also consider follow-ups are important in these patients. PMID- 26823808 TI - An insight into insulin-like factor 3 regulate its receptor RXFP2 in mouse gubernaculum testis cells. AB - The etiology of testicular dysgenesis syndrome is multifactorial and involves abnormalities in the anatomical structures and endocrine factors. Several studies have shown that the abnormal development of the gubernaculum may affect testicular descent, and the insulin-like factor 3 (INSL3) appears to play an important role in development of the gubernaculum have been proved. INSL3 binds its specific receptor (Relaxin family peptide 2, RXFP2), which was highly expressed in gubernaculum, to produce a crucial effect in the first transabdominal descent stage, but its mechanism still remain unclear. In this study, in order to explore how does INSL3 regulate its receptor RXFP2, we cultured mouse gubernaculum testis cells in vitro, which was treated by INSL3, and examined the expression of RXFP2 in mouse gubernaculum testis cells. The results displayed that INSL3 changed RXFP2 expression, and we found that low dose INSL3 can increase RXFP2 expression, the mechanism of above-mentioned might be related with the hormesis of INSL3. PMID- 26823809 TI - Diagnostic value of the plasmatic ADM level for early ectopic pregnancy. AB - OBJECTIVE: To analyze the plasmatic ADM level in early pregnancy and to investigate the diagnostic value of ADM in early ectopic pregnancy (EP). METHODS: 70 patients with EP who had menopause for 5~8 weeks were included as study group, while 155 women with normal intrauterine pregnancy were also included as control group. The correlation between ADM level and menopause weeks was statistically analyzed and ROC curve was used to identify the diagnostic value of ADM. RESULTS: (1) In 155 cases of normal intrauterine pregnancy, the plasmatic ADM level was increased with menopause weeks in linear relationship, and the correlation coefficient (R) was 0.991 (P<0.05). In 70 patients with EP, no significant increase was found with menopause weeks and no linear relationship can be found between ADM level and menopause weeks in EP group. The correlation coefficient (R) was 0.744 (P>0.05). (2) The multiple of median of plasmatic ADM level in EP group of menopause for 8 weeks was obviously lower than the intrauterine control group (P<0.01). (3) ROC curve was used to analyze the cut-off value of ADM level in the diagnosis of EP, and the area under the ROC curve was 0.523 (P>0.05) regardless of menopause weeks, however, the area under the ROC curve was 0.702 (P<0.05) at 8 weeks after menopause with sensitivity of 53.50% and specificity of 85.00%. CONCLUSIONS: Different from normal intrauterine pregnancy, plasmatic ADM level in early EP was relatively lower and no significant increase was found with menopause weeks; further studies are still needed for plasmatic ADM level as an indicator in the early diagnosis of EP. PMID- 26823810 TI - High expression of myofibrillogenesis regulator-1 predicts poor prognosis for patients with hepatocellular carcinoma after curative hepatectomy. AB - Myofibrillogenesis regulator (MR-1) is overexpressed in human cancer cells and plays an essential role in cancer cell growth. However, its role in hepatocellular carcinoma (HCC) has not yet been explored. The aim of this study was to investigate the association of MR-1 expression with clinicopathologic features and prognosis in patients with HCC. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to detect MR-1 mRNA levels in tissues samples from 120 HCC patients. Results showed that MR-1 expression was significantly higher in HCC tissues when compared with matched adjacent normal tissues (P=0.004). In HCC cancerous tissues, it was also significantly associated with tumor size (P=0.024) and serum AFP level (P=0.003). Moreover, Kaplan-Meier analysis showed that HCC patients with high MR-1 expression had shorter overall survival time than those with low MR-1 expression (P=0.009). When analyzed with a multivariate Cox regression model, MR-1 was identified as an independent prognostic factor for overall survival. Furthermore, when combined with serum AFP level, the median survival time significantly differed between patients with baseline high serum AFP and high MR-1 expression levels and those with normal AFP and low MR-1 levels (P=0.007). Taken together, our results suggest that high expression of MR-1 is involved in HCC progression and could be a novel biomarker of poor prognosis in patients with HCC. PMID- 26823811 TI - Expression of NF-kappaB-inducing kinase in breast carcinoma tissue and its clinical significance. AB - OBJECTIVE: To investigate the expression of nuclear factor-kappaB-inducing kinase (NIK) in breast carcinoma tissue and tumor-adjacent normal breast tissue and evaluate its clinical significance. METHODS: Surgically resected tissue specimens were collected from 82 patients with breast carcinoma who underwent surgical treatment at our hospital from March 2001 to December 2009. The diagnoses of all patients were confirmed by postoperative pathological examinations. NIK protein expression in breast carcinoma tissue and adjacent normal breast tissue was detected by immunohistochemistry; the association between NIK expression and the clinicopathological features and prognosis of patients with breast carcinoma was examined. RESULTS: The positive expression rate of NIK in breast carcinoma tissue was significantly higher than that in normal tissue (63.4% vs. 25.6%, P < 0.05). Additionally, NIK expression showed no relationship to the tumor size, age, degree of differentiation, or pathological type; however, it showed a significant correlation with lymph node metastasis and the clinical stage of patients (P < 0.05). The five-year survival rate was significantly lower in breast carcinoma patients who were positive for NIK expression than in those who were negative for NIK expression (P = 0.006). CONCLUSION: NIK expression was significantly increased in the tumor tissue of patients with breast carcinoma, which may be an important factor that affects the prognosis of these patients. PMID- 26823812 TI - Decreased expression of serum miR-424 correlates with poor prognosis of patients with hepatocellular carcinoma. AB - BACKGROUND: MicroRNAs (miRNAs) play important roles in many important cellular processes and deregulation of miRNAs is linked to many human diseases including cancer. Although miR-424 has been demonstrated to inhibit progression of hepatocellular carcinoma (HCC), its expression level in serum samples and the potential clinical values remain unknown. MATERIALS AND METHODS: The expression level of miR-424 in the serum clinical samples from HCC patients and healthy volunteers were determined by qRT-PCR. Then the association of serum miR-424 expression level with various important clinicopathological parameters and survival rates was evaluated. Multivariate Cox regression analysis was used to identify the independent risk factors for HCC. RESULTS: The expression level of serum miR-424 was significantly decreased in patients with HCC compared with the healthy volunteers (P<0.01). Reduced expression of serum miR-424 was associated with serum AFP (P=0.048), vein invasion (P=0.006) and TNM stage (P=0.003). In addition, survival analysis showed that HCC patients with lower serum miR-424 expression suffered poorer overall survival (P=0.018) and disease free survival (P=0.008). Moreover, serum miR-424 was demonstrated to be an independent risk factor for HCC. CONCLUSIONS: Our findings provide the compelling evidence that the decreased expression of serum miR-424 may serve as a novel biomarker to predict the unfavorable prognosis of HCC patients. PMID- 26823813 TI - Primary bone natural killer/T cell lymphoma, nasal type without EBV infection: a case report. AB - Primary bone NK/T cell lymphoma is very rare. We report a case of 52-year-old man of primary bone NK/T cell lymphoma and then progressed to NK leukemia. The patient had low-grade fever for 4-month, and Ultrasonic B revealed a diffuse hepatosplenomegaly without lymphadenopathy. PET scanning showed increased FDG uptake in many bones of the whole body. The diagnosis was established by bone specimen. These neoplastic cells demonstrated a typical immunophenotype of CD56, CD3, CD2 and MPO positive, and CD5, CD20, CD30, PAX-5, CD4 and CD8 negative. Primary bone ENKTL is very rare; it should be made with the combination of clinical feature, PET-CT image, and pathological characteristics, and should be distinguished from other lymphomas or leukemia involved in bone. PMID- 26823814 TI - Invasive fungal disease in university hospital: a PCR-based study of autopsy cases. AB - Invasive fungal disease (IFD) has high mortality rate, especially in the growing population of immunocompromised patients. In spite of introduction of novel diagnostic approaches, the intravital recognition of IFD is challenging. Autopsy studies remain a key tool for assessment of epidemiology of visceral mycoses. We aimed to determine species distribution and trends of IFD over the last 10 years in unselected autopsy series from a large university hospital. Forty-five cases of visceral mycoses, confirmed by histopathology and panfungal PCR, were found in 587 consecutive autopsies. Major underlying diseases were diabetes mellitus (20%), hematologic malignancies (15.6%) and systemic lupus erythematosus (15.6%). There was a high risk for disseminated IFD in immunocompromised patients stayed in the hospital over 1 month with a fever longer than 3 weeks. The most common fungi were Aspergillus spp. (58%), Candida spp. (16%), Mucorales (14%) and Fusarium spp. (10%). We found significant increase in Aspergillus flavus (P = 0.04) and Mucorales (P < 0.01) infections over the last 5 years. Concordance rate between histopathology and panfungal PCR was 89.5% to the genus level. All 6 cases of fusariomycosis were misinterpreted as aspergillosis by histology alone. The precise species identification, necessary for targeted antifungal treatment, was rendered only by the molecular technique. Panfungal PCR showed high performance on formalin-fixed paraffin-embedded specimens, providing important epidemiological data in retrospective autopsy series. Rapid detection of fungi by panfungal PCR assay has high potential for intravital diagnostics of IFD in surgical and biopsy specimens. PMID- 26823816 TI - DNA methyltransferase 3a rs1550117 genetic polymorphism predicts poor survival in gastric cancer patients. AB - DNA methyltransferase 3a (DNMT3a) have been suggested to play a crucial role in human cancer prognosis. Single nucleotide polymorphisms (SNPs) in DNMT3a genes may have an impact on the prognosis of cancers. This study aimed to investigate the association between SNPs of DNMT3a gene and prognosis of gastric cancer (GC). Two sites of DNMT3a SNPs, rs1550117 and rs13420827 were selected and genotyped using TaqMan assay in 447 GC patients who received gastrectomy. Effects of genotypes on clinical outcomes of GC were calculated by Kaplan-Meier survival analysis and Cox regression model. We found that the AG or AA genotype of rs1550117 was associated with significantly poorer survival and increased death risk of GC compared with GG genotype (dominant model: HR=1.35, 95% CI=1.01-1.80, P=0.043). Further multivariate Cox regression analysis revealed that in addition to the known factors including male, larger tumor sizes and high clinical stage, rs1550117 variant was an independently predictive factor for survival in GC patients. No significant association was found between rs13420827 genetic variants and GC prognosis. Our findings first demonstrated that DNMT3a rs1550117 polymorphism may be a potential biomarker in predicting overall survival of GC patients. PMID- 26823815 TI - Combined detection of preoperative serum CEA, CA19-9 and CA242 improve prognostic prediction of surgically treated colorectal cancer patients. AB - We assessed the prognostic significance of preoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 242 (CA242) levels in surgically treated colorectal cancer patients. The relationship of preoperative serum CEA, CA19-9 and CA242 levels with disease characteristics was investigated in 310 patients. Correlation between tumor markers was investigated using Pearson correlation test. Univariate and multivariate survival analyses were used to study the relationship between preoperative tumor markers and prognosis [disease free survival (DFS) and overall survival (OS)]. Kaplan Meier analysis with log rank test was used to assess the impact of tumor marker levels on survival. Positive rate of preoperative serum CEA, CA19-9 and CA242 were 54.84%, 47.42% and 37.10%, respectively. High preoperative CEA level was associated with tumor size (P = 0.038), T stage (P < 0.001) and AJCC stage (P = 0.002). High preoperative CA19-9 level was associated with tumor AJCC stage (P = 0.023). Preoperative CA242 positively correlated with CEA (P < 0.001) and CA19-9 (P < 0.001). Combining the three markers was of independent prognostic value in CRC (HR = 2.532, 95% CI: 1.400-4.579, P = 0.002 for OS; and HR = 2.366, 95% CI: 1.334-4.196, P = 0.003 for DFS). Combined detection of preoperative serum CEA, CA19-9 and CA242 is of independent prognostic value for management of CRC patients treated surgically. PMID- 26823817 TI - Evaluation of AKT phosphorylation and PTEN loss and their correlation with the resistance of rituximab in DLBCL. AB - BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma with quite high mortality. PTEN/PI3K/AKT signal pathway is constitutively activated and plays an oncogenic role in most tumors including non Hodgkin's lymphoma (NHL). Since rituximab used in chemotherapy has been proved to improve the survival of DLBCL patients, rituximab resistance is a common clinical challenge in the treatment of DLBCL. The aims of the present study are to determine the different levels of several important biomarkers of PTEN/PI3K/AKT pathway in DLBCL patients who are resistant or sensitive to rituximab treatment, and investigate the potential clinical application of these biomarkers. METHODS: 48 patients with DLBCL who were treated by rituximab-based chemotherapy were divided into 2 groups according to their reactions to rituximab. The expression of p-AKT, PTEN, and Ki-67 protein in 48 DLBCL tissues were detected using immunohistochemistry and analyzed for the clinical pathological significance and the resistance to rituximab. Meanwhile, PTEN gene deletion was detected also by FISH, and mutation of PIK3CA was performed by sequencing analysis. RESULTS: Activation of p-AKT in 12 of 48 (25.0%) and loss expression of PTEN in 15 of 48 (31.3%) DLBCL species were observed. P-AKT activation (P<0.05) and loss of PTEN expression (P<0.05) were significantly associative with high Ki-67 index. P-AKT and PTEN expression showed a significant negative correlation in all 48 DLBCL patients (r=-0.450, P<0.05), and the Spearman correlation coefficient in the resistant group (r=-0.769, P<0.05) was greater than in the sensitive group (r= 0.691, P<0.05). CONCLUSION: Regulation of PTEN/PI3K/AKT signal pathway participates in the progression of DLBCL, and may be involved in the development of the resistance to rituximab for some DLBCL patients. PMID- 26823818 TI - P15, MDM2, NF-kappaB, and Bcl-2 expression in primary bone tumor and correlation with tumor formation and metastasis. AB - Primary bone tumor is one of the most common malignant tumors in skeletal system. It seriously affected bone movement and development with unclear pathogenesis. In this paper, rabbit VX-2 malignant bone tumor model was applied to explore apoptotic genes P15, MDM2, NF-kappaB and Bcl-2 correlation with primary bone tumor occurrence and metastasis. 0.3 ml rabbit VX-2 tumor cell suspension (1*10(6)/ml) was injected to the marrow cavity of the right tibia condyle to establish the rabbit malignant bone tumor model, while equal amount of the saline was injected to the left tibia as control. Real-time PCR was applied to determine P15, MDM2, NF-kappaB and Bcl-2 expression level. Immunohistochemistry was performed to detect the abovementioned genes expression in lung, stomach, kidney and bladder. Compared with control, P15 expression level in the inoculation site surrounding tissues decreased obviously following the inoculate time elongation (P<0.05), while Bcl-2, MDM2 and NF-kappaB expression significantly increased (P<0.05). Bcl-2 showed significant correlation with MDM2 and NF-kappaB (P<0.05). At the 2, 4, 6 weeks, Bcl-2, MDM2 and NF-kappaB in lung, Bcl-2 in kidney, and Bcl 2 and MDM2 in bladder positively expressed (P<0.05), whereas P15 gene exhibited no significant positive expression in these tissues (P>0.05). P15, MDM2, NF kappaB, and Bcl-2 genes expression levels can effectively reflect malignant bone tumor growth of rabbit tibia. MDM2, NF-kappaB and Bcl-2 genes involved in primary bone tumors metastasis directly. It has important clinical significance for early diagnosis and treatment of primary bone tumor. PMID- 26823819 TI - Prognostic significance of preoperative C-reactive protein: albumin ratio in patients with clear cell renal cell carcinoma. AB - We undertook a retrospective analysis to evaluate the C-reactive protein/albumin (CRP/Alb) ratio for its prognostic value in patients with clear cell renal cell carcinoma (CCRCC). The study comprised 406 CCRCC patients undergoing nephrectomy between 2003 and 2012 in our hospital. The correlations among the pretreatment CRP/Alb ratio, clinicopathological parameters, and overall survival (OS) were evaluated. An elevated CRP/Alb ratio was associated with older age at surgery (P=0.007), more advanced TNM stage (P<0.001), more presence of tumor necrosis (P<0.001) and lymphovascular invasion (P<0.001), lower concentration of hemoglobin (P<0.001) and calcium (P=0.005), and shorter OS (P<0.001). The multivariate analysis confirmed that the CRP/Alb ratio independently predicted the OS of patients with CCRCC (P<0.001), the Glasgow Prognostic Score (GPS) (P=0.001) and modified GPS (mGPS) (P=0.019) were independent prognostic factors also. At last, we evaluated the prognostic value of the CRP/Alb ratio compared with the similar inflammation-based prognostic scores GPS and mGPS using the area under the curve (AUC). Although the differences were not statistically significant, the AUC value of the CRP/Alb ratio (continuous, categorical) was higher compared with the GPS and mGPS, except that the AUC value for the CRP/Alb ratio (categorical) at 3 years was lower than that for the GPS. The CRP/Alb ratio could take the place of the GPS and mGPS in terms of predicting prognosis in CCRCC. PMID- 26823820 TI - Fibroblast growth factor-21 is positively associated with atrial fibrosis in atrial fibrillation patients with rheumatic heart disease. AB - OBJECTIVE: Fibroblast growth factor-21 (FGF-21) has been discovered as a strong hormone, plays an important role in lipid metabolism, glucose metabolism, associated with several diseases such as obesity, metabolic syndrome, diabetes mellitus, and cardiovascular events; however, no evidence is available concerning the relationship of FGF-21 and atrial fibrosis in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD). METHODS: Twenty-four rheumatic heart disease patients were divided into two groups, 12 cases with AF and 12 cases with sinus rhythm (SR). Clinical characteristics and blood samples were collected before surgery; right atrial appendage samples were taken in the surgery of valve replacement. HE staining was performed to determine cross sectional area of atrial myocytes; Masson stained sections and mRNA levels of cardiac fibrosis biomarkers were used to evaluate the degree of cardiac fibrosis; the level of FGF-21 was evaluated via enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and real-time polymerase chain reaction (PCR). RESULTS: Compared with SR group, cross-sectional area of atrial myocytes and collagen volume fraction were significantly increased in the atrial tissue of AF group. The distribution of FGF-21 in the AF group was remarkably higher than SR group. In addition, plasma and mRNA levels of FGF-21 in atrial tissue of AF showed the same trend as the result of immunohistochemistry. Using linear correlation analysis, the expression level of FGF-21 was found to be positively related to the degree of atrial fibrosis. CONCLUSION: FGF-21 might involve in the development and maintenance of atrial fibrosis in atrial fibrillation with rheumatic heart disease, and FGF-21 could be used as a novel biomarker to evaluate myocardial fibrosis in the future. PMID- 26823821 TI - Role of GSTP1 Ile105Val and XRCC1 Arg194Trp, Arg280His and Arg399Gln gene polymorphisms in the clinical outcome of advanced non-small cell lung cancer. AB - We conducted a study to investigate the association between the clinical outcome and GSTP1 Ile105Val and XRCC1 Arg194Trp, Arg280His and Arg399Gln gene polymorphisms in advanced NSCLC patients with cisplatin-based chemotherapy. Between January 2010 and December 2012, a total of 206 patients with advanced NSCLC were histopathologically confirmed were included into analysis. By logistic regression analysis, individuals carrying the AG and GG genotypes of GSTP1 Ile105Val were associated with better response to chemotherapy when compared with the AA genotype, and the adjusted Ors (95% CI) were 2.06 (1.10-3.86) and 4.89 (1.52-18.33), respectively. The TT genotype of XRCC1 Arg194Trp was correlated with better response to chemotherapy compared to the CC genotype, and the adjusted OR (95% CI) was 3.23 (1.20-9.30). By Cox Hazard Proportional Model, the GG genotype of GSTP1 Ile105Val and the TT genotype of XRCC1 Arg194Trp were found to be associated with lower risk of death from all causes when compared with the wide-type genotype, and the adjusted HRs (95% CI) were 0.05 (0.01-0.18) and 0.20 (0.07-0.62), respectively. Moreover, individuals carrying both the G/A+G/G genotype of GSTP1 Ile105Val and the G/A+A/A of XRCC1 Arg194Trp were associated with heavy greater CR+PR response to chemotherapy (OR=2.98, 95% CI=1.39-6.42), and also correlated with longer overall survival of advanced NSCLC (HR=0.19, 95% CI=0.05-0.61). In conclusion, we found that the GSTP1 Ile105Val and XRCC1 Arg194Trp were associated with better response to chemotherapy and longer survival of advanced NSCLC, compared to the wide-type genotype. PMID- 26823822 TI - Single nucleotide polymorphism of NKX2-5 gene with sporadic congenital heart disease in Chinese Bai population. AB - BACKGROUND: Congenital heart disease (CHD) is the most common birth abnormality, especially for sporadic CHD. However, the etiology of sporadic CHD is largely unknown. NKX2-5, the earliest sign of cardiac progenitor cell differentiation, plays a key role in cardiac morphogenesis, and the mutation of this gene can cause sporadic CHD. PURPOSE: To investigate the association of genetic variations of NKX2-5 with sporadic CHD in Chinese Bai people. METHODS: The whole 2 coding exons and flanking intron sequences of NKX2-5 gene were screened using DNA sequencing in 70 Chinese Bai patients with sporadic CHD and 136 healthy controls. RESULTS: A novel heterozygous DNA sequence variant (DSV), 1433A>G, was identified in one tetralogy of Fallot (TOF) patient and one persistent left superior vena cava (PLSVC) patient, but none in controls. The frequency of single nucleotide polymorphism (SNP) rs2277923 in CHD group was significantly higher than that in control group. The allele and genotype were associated with the occurrence of CHD. CONCLUSION: The novel DSV (1433A>G) may be relevant with TOF and PLSVC, and the SNP rs2277923 of NKX2-5 gene contributes to the risk of sporadic CHD in Chinese Bai people. PMID- 26823824 TI - C-MET overexpression and amplification in gliomas. AB - We investigated c-Met overexpression and MET gene amplification in gliomas to determine their incidence and prognostic significance. c-Met immunohistochemistry and MET gene fluorescence in situ hybridization were carried out on tissue microarrays from 250 patients with gliomas (137 grade IV GBMs and 113 grade II and III diffuse gliomas). Clinicopathological features of these cases were reviewed. c-Met overexpression and MET gene amplification were detected in 13.1% and 5.1% of the GBMs, respectively. All the MET-amplified cases showed c-Met overexpression, but MET amplification was not always concordant with c-Met overexpression. None of grade II and III gliomas demonstrated c-Met overexpression or MET gene amplification. Mean survival of the GBM patients with MET amplification was not significantly different from patients without MET amplification (P=0.155). However, GBM patients with c-Met overexpression survived longer than patients without c-Met overexpression (P=0.035). Although MET amplification was not related to poor GBM prognosis, it is partially associated with the aggressiveness of gliomas, as MET amplification was found only in grade IV, not in grade II and III gliomas. We suggest that MET inhibitor therapy may be beneficial in about 5% GBMs, which was the incidence of MET gene amplification found in the patients included in this study. PMID- 26823823 TI - Influence of protein kinase C (PKC) on the prognosis of diabetic nephropathy patients. AB - AIMS: To investigate the association between protein kinase C (PKC) and the prognosis of patients with diabetic nephropathy (DN). METHODS: 92 patients with DN who had received treatments with angiotensin converting enzyme inhibitor (ACEI) or angiotensin-receptor blockade (ARB) were collected. The clinicopathologic characteristics were recorded and a 4-year follow-up with the final result of impaired renal functions (eGFR < 40 mL/min) was conducted. The expression of PKC was detected by immunohistochemical assay. Kaplan-Meier and Cox regression analysis were performed to estimate the effects of PKC on DN prognosis. RESULTS: According to immunohistochemical analysis, there were 54 cases with positive expression of PKC (positive rate 58.7%). Meanwhile, during the follow-up, the urine protein, mean serum creatinine and eGFR in patients with positive PKC were all higher than those in negative expression group (P < 0.05). The expression of PKC was influenced by age (P < 0.001), course of disease (P < 0.001), blood pressure (P = 0.002), blood glucose (P < 0.001), HbA1c (P = 0.002), renal functions of patients before (P = 0.011) and after (P = 0.041) the biopsy. Besides, the Kaplan-Meier curve revealed that patients with positive PKC expression had shorter survival time than those with negative PKC expression (P < 0.001). Cox regression analysis indicated that HbA1c (P = 0.009), renal functions of patients after the biopsy (P = 0.002) and PKC (P = 0.028) were important factors in the prognosis of DN and they might be independent prognostic markers. CONCLUSION: The expression of PKC is relatively higher in DN patients than in healthy controls. And PKC may be a valuable prognostic marker for patients with DN. PMID- 26823825 TI - DAPK1, MGMT and RARB promoter methylation as biomarkers for high-grade cervical lesions. AB - Gene promoter methylation may be used a potential biomarker for detecting solid tumor including cervical cancer. Here, we used methylation sensitive-high resolution melting (MS-HRM) analysis to detecting promoter methylation ratios of DAPK1, MGMT and RARB gene in patients with different cervical disease grade. The detection of gene promoter methylation was conducted in two hundred fifty patients' samples including normal cytology (n=48), cervical intraepithelial neoplasia grade 1 (CIN1, n=54), cervical intraepithelial neoplasia grade 2 (CIN2, n=47), cervical intraepithelial neoplasia grade 3 (CIN3, n=56) and cervical squamous cell carcinomas (SCS, n=45). We found there were a significant positive correlation between the promoter methylation status of DAPK1 and cervical disease grade (P=0.022). In addition, the methylated promoters of DAPK1 combined with MGMT, MGMT combined with RARB, DAPK1 combined with RARB were positive correlated with cervical disease grade (P < 0.05). All three genes promoters methylated were positive correlated with cervical disease grade (P < 0.001). Receiver operating characteristic (ROC) curves was conducted to evaluate whether the three genes methylation could be used to be a potential marker for diagnosing high grade cervical disease (HSIL and SCC). The cutoff values for the methylation rates of all these genes were 0-5%. Regrettably, only the methylation of MGMT combined with DAPK1 gave 43.4% sensitivity and 68.6% specificity. The current results indicated that MS-HRM-based testing for DNA methylations of MGMT plus DAPK1 genes holds some promise for high grade cervical disease screening. PMID- 26823826 TI - Curcumin inhibits the proliferation and invasion of human osteosarcoma cell line MG-63 by regulating miR-138. AB - OBJECTIVE: In this study, we screened the different human osteosarcoma cell line MG-63 miRNAs after the treatment of curcumin and explored the effects of curcumin on MG-63 cells and its mechanism. METHODS: Affemitrix miRNA chip was used to detect the changes of miRNA expression profile in MG-63 cells before and after curcumin treatment, and screen different expression of miRNAs. The target gene of miRNA was analyzed by bioinformatics. The expression levels of miRNA-138 target genes Smad4, NFkappaB p65 and cyclin D3 were detected. MTT and Transwell Cell invasion assays were used to observe the effects of curcumin on MG-63 cells. RESULTS: Curcumin could significantly inhibit the proliferation of MG-63 cells and the expression levels of miRNA-138 target genes Smad4, NFkappaB p65 and cyclin D3 in MG-63 cells (P<0.05); overexpression of hsa-miR-138 down-regulated the expression levels of Smad4, NFkappaB p65 and cyclin D3 compared with the treatment of curcumin, while inhibition of hsa-miR-138 up-regulated the expression levels of Smad4, NFkappaB p65 and cyclin D3. CONCLUSIONS: Curcumin could increase the expression of hsa-miR-138, hsa-miR-138 inhibited cell proliferation and invasive ability by inhibition of its target genes. PMID- 26823827 TI - Association between MUC5B polymorphism and susceptibility and severity of idiopathic pulmonary fibrosis. AB - OBJECTIVES: Idiopathic pulmonary fibrosis (IPF) is a group of lung diseases that cause irreversible architectural distortion and impair gas, and finally progressive pulmonary functional decline and death, in which the common variant in the promoter region of the mucin 5B (MUC5B) gene may be involved. The present study aims to investigate whether variants within the MUC5B gene rs35705950 contributed to IPF susceptibility and severity in Chinese Han Population. METHODS: A total of 187 patients diagnosed with IPF and 250 healthy controls were enrolled in this study. All subjects were genotyped for MUV5B SNP rs35705950. The demographic, comorbidity, clinical and functional data were recorded. RESULTS: The rs35705950 of MUC5B were found significantly associated with increased risk of IPF susceptibility. One way ANOVA analysis found that there was a significant decreased FVC (P < 0.0001) and DLco (P < 0.0001) in correction with the minor allele of the SNP rs35705950. In the 5 years' follow-up, the carriers of the minor allele T increased mortality (P = 0.0294). CONCLUSION: This study demonstrated that the MUC5B polymorphism rs35705950 is associated with increased risk of idiopathic pulmonary fibrosis susceptibility, severity, and the decreased overall survival. PMID- 26823828 TI - Application of serum NY-ESO-1 antibody assay for early SCLC diagnosis. AB - BACKGROUND: NY-ESO-1 antibody is one of the cancer-related antibodies. The purpose of this study was to investigate the diagnostic role of the NY-ESO-1 humoral immune response in small cell lung cancer (SCLC). METHODS: We recombined the recombinant protein of NY-ESO-1 antibody and NSE, analyzed them by Enzyme linked immunosorbent assay, and then established the Receiver Operating Characteristic (ROC) curve to estimate the diagnostic value of NY-ESO-1 antibody, NSE and their combinations. RESULTS: According to detection, the positive rate of NY-ESO-1 humoral immune response (26.3%), NSE (43.8%) and their combinations (10.5%) were all lower than the negative rate which indicated that the NY-ESO-1 antibody might be down-regulated in SCLC. And the positive rate wasn't related to clinicopathologic characteristics. The ROC curve demonstrated that with a 37.17% sensitivity and a 91.7% specificity along with a AUC of 0.619 for NY-ESO-1ab as well as with a 48.3% sensitivity and a 90.87% specificity along with a AUC value of 0.773 for NSE, their diagnostic value were both high. Besides, the diagnostic value of their combinations was also good for a AUC of 0.83 and a 69.12% sensitivity and a 91.8% specificity. There were significant difference of diagnostic value among three types above (NY-ESO-1 vs. NSE, P < 0.01; The Combinations vs. NY-ESO-1, P < 0.0001; and the Combinations vs. NSE, P < 0.04). CONCLUSION: In conclusion, NY-ESO-1ab, NSE and their combinations all were important diagnostic markers for SCLC. Moreover, the diagnostic value of their combinations was higher than any single of them. And NY-ESO-1 humoral immune to NSE might be a potential diagnostic indicator in SCLC. PMID- 26823829 TI - Association of MMP-2 expression and prognosis in osteosarcoma patients. AB - OBJECTIVE: Our aim was to investigate the MMP-2 expression and its prognostic value in osteosarcoma patients. METHODS: We performed RT-qPCR to detect the expression of MMP-2 in 45 paired osteosarcoma tissues and adjacent noncancerous tissues. Immunohistochemical staining assay was used to verify the expression of MMP-2 protein in osteosarcoma patients. Independent-sample T test was used to analyze the difference of MMP-2 expression level between osteosarcoma and control groups. The relationship between clinicopathologic factors and MMP-2 expression was analyzed by chi-square test. Kaplan-Meier was performed to analyze the association of MMP-2 expression and overall survival rate. The prognostic value of clinicopathologic factors and MMP-2 was estimated via Cox regression analysis. RESULTS: RT-qPCR revealed that the expression of MMP-2 was up-regulated in osteosarcoma group compared with the control group. Besides MMP-2 expression was influenced by pulmonary metastasis (P<0.05) while gender, age, tumor site and Enneking stage showed no obvious impact (P>0.05). Kaplan-Meier curve revealed that patients with positive MMP-2 expression had a shorter survival time than those with negative MMP-2 expression, and the survival rates were 18.5% (5/27) and 44.4% (8/18), respectively. Cox regression analysis indicated that pulmonary metastasis and expression of MMP-2 gene were important factors in the prognosis of osteosarcoma. CONCLUSION: The expression of MMP-2 was associated with pulmonary metastasis, and was related to the prognosis of osteosarcoma. MMP-2 could act as an independent prognostic marker in osteosarcoma patients. PMID- 26823830 TI - Expression of phosphorylated Akt and hTERT is associated with prognosis of epithelial ovarian carcinoma. AB - Activation of human telomere reverse transcriptase (hTERT) is associated with the tumorigenic role of Akt. We aimed to evaluate the significance of Akt phosphorylation and hTERT expression on the prognosis of epithelial ovarian cancer (EOC). Between 2005 and 2012, 92 EOC patients treated at the Seoul National University Hospital were included in this study. Paraffin-embedded sections from the tumors of EOC patients were stained with anti-hTERT and anti phosphorylated Akt (pAkt) antibodies. Correlations of pAkt and hTERT expression with the clinicopathological factors were analyzed using SPSS software, version 17.0 (IBM, Chicago, IL, USA). In 92 EOC tissues, pAkt and hTERT were not associated with any clinicopathological factors. However, the disease-free survival rate of patients exhibiting coexpression of pAkt and hTERT was poor compared with that of the other patients (P = 0.013). Coexpression of pAkt and hTERT is a poor prognostic marker for EOC. PMID- 26823831 TI - Implication of Reprimo and hMLH1 gene methylation in early diagnosis of gastric carcinoma. AB - DNA methylation has been recently recognized as a novel tumor marker. This study investigated the methylation status of Reprimo and hMLH1 gene in both plasma and tissue samples from gastric cancer patients, in an attempt to investigate their diagnostic implications in gastric cancer. A total of 180 tissue and plasma samples (including 50 cases of gastric cancer, 50 dysplasia, 50 chronic atrophic gastritis with intestinal metaplasia and 30 normal controls) were collected for detecting DNA methylation status of Reprimo and hMLH1 genes using MSP method. Tissue protein expression levels were further tested by immunohistochemical (IHC) staining. The positive rate of DNA methylation rate was, in ascending sequence, gastritis tissue, dysplasia tissue and gastric carcinoma tissue. All those tissues had significantly elevated DNA methylation level compared to normal group (P < 0.05). Expression level of Reprimo and hMLH1 proteins were, however, decreased in pathological tissues compared to normal ones (P < 0.05). A significantly negative relationship existed between protein level and promoter region methylation level. The DNA methylation occurred in promoter regions of both Reprimo and hMLH1 genes depressed the protein expression, and may participate in the occurrence and progression and gastric cancer. The combined assay of serum Reprimo and hMLH1 DNA methylation levels thus had critical importance in the early diagnosis and gastric cancer. PMID- 26823832 TI - Down-regulation of microRNA-126 and microRNA-133b acts as novel predictor biomarkers in progression and metastasis of non small cell lung cancer. AB - OBJECTIVE: MiRNAs play crucial roles in progression of cancer. However, the underlying mechanisms of miRNAs in non small cell lung cancer are still poorly understood. The aim of this study was to investigate the expression level of microRNA-126 (miR-126) and microRNA-133b (miR-133b) and also their association with clinicopathological features in patients with non small cell lung cancer (NSCLC). METHODS: Total RNA was purified from NSCLC tissues and adjacent non tumor tissues and then quantitative real-time PCR (qRT-PCR) was used to evaluate the expression rate of microRNAs. Furthermore, the association of miR-126 and miR 133b level with clinicopathological features and prognosis were evaluated. RESULTS: Our findings showed that expression of miR-126 was decreased in NSCLC tissues compared with adjacent non-tumor tissues. On the other hand, a lower expression of miR-133b was seen in NSCLC tissues when compared with adjacent non tumor tissues. In term of miR-126, our results showed that miR-126 was associated with tumor stage and lymph nodes metastasis (P<0.05). In term of miR-133b, our finding indicated that decreased expression of miR-133b was correlated with advanced tumor stage and lymph nodes metastasis (P<0.05). Kaplan-Meier analysis and log-rank test indicated that patients with low expression of miR-126 and miR 133b had a shorter overall survival (log-rank test; P<0.05). Multivariate Cox proportional hazards model revealed that low expression of miR-126 and miR-133b, advanced tumor stage and lymph nodes metastasis were independent prognostic factors for overall survival of NSCLC patients. CONCLUSIONS: These findings suggested that miR-126 and miR-133b might play a key role in the progression and metastasis of NSCLC and would be applied as a novel therapeutic agent. PMID- 26823833 TI - Clinical implications of beta-catenin protein expression in breast cancer. AB - The objective of this study was to examine the expression and significance of beta-catenin in the diagnosis and prognosis of breast cancer. Overall, 241 patients with histologically confirmed breast cancer who had undergone radical surgery were enrolled in this study. beta-catenin protein expression in breast cancer samples was evaluated by immunohistochemistry. beta-catenin was expressed in Nuclei/Plasma of the samples from 41 patients. beta-catenin protein expression correlated with the histological grade of the tumor (P<0.05) and Ki-67 labeling (P<0.01). Survival analysis showed that beta-catenin expression negatively correlated with breast cancer-specific survival. Our results showed prominent expression of beta-catenin in breast cancer and strongly implicate the beta catenin in tumor promotion. PMID- 26823834 TI - Association of RNF43 with cell cycle proteins involved in p53 pathway. AB - Our previous study has demonstrated that RNF43 could regulate the cell cycle in a p53-dependent manner in HCC. In this study, we aimed to access whether RNF43 could interact with cell cycle proteins involved in p53 pathway, including pRB, Cyclin D1 and MDM2. Totally, 123 paired HCC tissues and corresponding noncancerous tissues from HCC patients were included, and the expression of Cyclin D1, pRB and MDM2 was analyzed using tissue microarray. Our results showed the expression level of RNF43 in HCC was positively correlated with that of MDM2, Cyclin D1 and pRB-S780. There was no significant correlation between the expression of RNF43 and pRB-S807/S811. Indicating that RNF43 effected cell cycling by regulating the expression of pRB, Cyclin D1 and MDM2 proteins, and pRB S780 but not pRB-S807/S811, was participated in RNF43 regulated cell cycling. PMID- 26823835 TI - Yolk sac tumor of the external auditory canal: a case report and literature review. AB - We report one case of yolk sac tumor of the ear and review the literature. The patient was a 9-month boy who scratched his right ear repeatedly one month ago. Computed tomography scan showed an irregular elongated mass image measuring 42*16 mm was found in the right external auditory canal. The tumor was located underneath of the epidermis with ulceration. Mild or moderate atypical round or oval tumor cells were arranged in nest and reticular pattern around vesicular or cystic spaces. Tumor cells had abundant eosinophilic or clear cytoplasm and marked nucleoli. Mitotic figures were about 7/10 HPF. Poorly formed Schiller Duvall body was occasionally present. The stroma was loose and rich in capillaries. Hyaline globules could be found in the stroma. Immunohistochemistry staining showed that tumor cells were positive for cytokeratin, SALL4, glypican 3, focal positive for EMA, vimentin, CD10, and CD34, but negative for a fetoprotein, HCG, PLAP. The serum alpha-fetoprotein was 664.60 ng/mL (normal, <= 25 ng/mL). Yolk sac tumor of the ear is extremely rare, especially alpha fetoprotein negative expression in our case. The differential diagnosis includes embryonal rhabdomyosarcoma, paraganglioma, myoepithelioma, carcinoma of skin appendages, and metastatic renal cell carcinoma. PMID- 26823836 TI - Relationship between CIP2A expression, and prognosis and MDR-related proteins in patients with advanced gastric cancer. AB - CIP2A is highly expressed in a variety of malignancies. We determined the expression and clinical significance of CIP2A in patients with advanced gastric cancer. CIP2A protein was expressed in 25 of 37 cancer tissue specimens. There was no correlation between CIP2A and PGP, GST-pi, Topo-II, and LRP expression. Survival analysis showed significant differences between the survival rate of the CIP2A protein-positive and -negative groups (chi(2)=4.509, P=0.034), but the degree of positive expression was unrelated to survival time (chi(2)=4.639, P=0.098). CIP2A expression may have no prospective value for optimizing chemotherapy regimens, but it can be an indicator for patient prognosis. PMID- 26823837 TI - Molecular epidemiological investigation of G6PD deficiency by a gene chip among Chinese Hakka of southern Jiangxi province. AB - In southern China, glucose-6-phosphate dehydrogenase (G6PD) deficiency is a significant health problem, and the incidence ranged from 0.5 to 4.08% in different Chinese population. The aims of this study are to investigate the molecular epidemiological characteristic of the G6PD gene among Chinese Hakka in southern Jiangxi province. 2331 unrelated subjects were screened for G6PD deficiency by a fluorescent test. DNA from deficient individuals was analyzed by a gene chip analysis for thirteen common Chinese G6PD mutations. In total, 3.60% (82/2331; 95% CI 2.77-4.27) of the sample were found to be G6PD-deficient. Eight mutations were found from 80 samples. However, mutation(s) for the two remaining samples were unknown. The most common mutations were G6PD Canton (1376 G>T) and G6PD Kaiping (1388 G>A), and the following mutations were 1311 polymorphism (1311 C>T), G6PD Gaohe (95 A>G), G6PD Chinese-5 (1024 C>T), G6PD Maewo (1360 C>T), Shunde (592 C>T), G6PD Viangchan (871 G>A) and Chinese-3 (493 A>G). This is the first report of G6PD deficiency among Chinese Hakka population in Jiangxi province. PMID- 26823838 TI - miR-21 expression predicts prognosis in diffuse large B-cell lymphoma. AB - BACKGROUND: Expression patterns of microRNAs in serum are involved in potentially biomarkers for various diseases. The aim of the study was to investigate the expression level of miR-21 in diffuse large B cell lymphoma (DLBCL) and its prognostic value. METHODS: Real-time quantitative polymerase chain reaction (qRT PCR) was used to measure miR-21 levels in serum samples from 112 patients with DLBCL as well as in serum samples from 45 healthy controls. The associations between miR-21 expression and clinicopathologic parameters and overall survival of the patients, were analyzed by chi-square test and Kaplan-Meier method. The Cox proportional hazards regression analyses were performed to estimate the prognostic values for patient survival prediction. RESULTS: We found that serum miR-21 expression was markedly upregulated in patients with DLBCL than healthy controls. Increased miR-21 expression was significantly correlated with B symptoms, IPI score, CHOP-like treatment and Rituximab (all Ps<0.05). Moreover, DLBCL patients with miR-21 higher expression have shown significantly worse overall survival than those with lower miR-21 expression. And miR-21 expression was an independent prognostic marker of overall survival in a multivariate analysis (P=0.001, HR: 4.404, 95% CI: 1.770-10.956). CONCLUSION: The results of the present study suggested miR-21 expression level could be a novel potential biomarker for DLBCL prognosis. PMID- 26823839 TI - A rare case of nasopharyngeal carcinoma in a patient with multiple myeloma after treatment by lenalidomide. AB - Multiple myeloma (MM) is a plasma-cell malignancy leading to a significant life expectancy shortening. Lenalidomide is an oral immunomodulatory drug (IMiD) approved in the United States for patients with MM. Although the introduction of lenalidomide combined with dexamethasone (Len/Dex) has improved the outcome of patients with relapsed/refractory multiple myeloma (RRMM), it is a common knowledge that lenalidomide has been linked to the development of secondary primary malignancies in the MM patients, especially in those who use lenalidomide as a maintenance therapy. In the published literature, these are also many cases reported by clinicians in different secondary primary malignancies after the diagnosis of MM treated with lenalidomide. In this present article, we provided our patient who was identified nasopharyngeal carcinoma (NPC) 46 months after the diagnosis of MM and 21 months after lenalidomide treatment. To the best of our knowledge, this is the first case report related to the occurrence of NPC in a patient with MM after treatment by lenalidomide. Although it is not very sure that the incidence of NPC was associated with the use of lenalidomide, we clinicians should pay adequate attention to this phenomenon in the clinical processing. And much more cooperative studies of large numbers of MM patients are needed to evaluate a possible association between lenalidomide and NPC. PMID- 26823840 TI - Effect of histone deacetylase on prostate carcinoma. AB - Commonly occurred in aged males, the incidence of prostate carcinoma is increasing by years. Histone deacetylase (HDACs) as one key enzyme in regulating gene transcription has been found to be related with cancer occurrence. Trichostatin A (TSA) is one HDAC inhibitor for suppressing tumor growth. This study thus treated prostate carcinoma cell line PC3 with TSA, to analyze the effect of HDAC on the occurrence and progression of HDAC. PC3 cells were treated with gradient concentrations of TSA. MTT assay was employed to detect the proliferation of PC3 cells, while flow cytometry was used to detect the cell apoptosis and cell cycle. Apoptotic proteins including caspase-3, caspase-9 and bcl-2 were further quantified by Western blotting. MTT assays showed a dose- and time-dependent manner of TSA in inhibiting PC3 cell proliferation. Most of PC3 cells were arrested at G1 phase after treating with TSA. The apoptotic ratio of cells was also elevated by higher concentrations of drugs. Apoptotic proteins including caspase-3, caspase-9 and bcl-2 were all up-regulated by TSA. HDAC inhibitor can effectively suppress the proliferation of prostate carcinoma cells, which can be arrested at G1 phase. The elevated apoptotic ratio was caused by up regulation of apoptosis-related proteins caspase-3, caspase-9 and bcl-2, in both dose- and time-dependent manners. PMID- 26823841 TI - Mixed lineage kinase domain-like protein is a prognostic biomarker for cervical squamous cell cancer. AB - BACKGROUND: The mixed lineage kinase domain-like protein (MLKL) has recently been identified as a key RIP3 (receptor interacting protein 3) downstream component of tumor necrosis factor (TNF)-induced necroptosis. OBJECTIVE: To evaluate the expression and clinical significance of MLKL in cervical squamous cell carcinoma. METHODS: The expression of MLKL in 54 cervical squamous carcinoma samples was detected by immuneohistochemical method. Chi-square, correlation analysis and kaplan-Meier method were used to analyze the data. RESULTS: The MLKL expression in cervical squamous cell carcinoma was higher than that in normal cervical tissues (P = 0.004). The MLKL expression was negatively correlated with histological grade, lymphatic metastasis (P<0.05). Survival analysis showed the low expression of MLKL indicated poor prognosis. CONCLUSION: MLKL was a prognostic biomarker for cervical squamous cell carcinoma. PMID- 26823842 TI - Perianal multiple Bowen's disease: a case report. AB - Bowen's disease, also known as an intraepithelial squamous cell neoplasia, is a carcinoma in situ firstly reported in 1912 by a dermatologist named Bowen from the United States [1]. About 3%~5% of Bowen's disease might develop into invasive squamous cell carcinomas of mocusa and skin [2]. Surgical resection is preferred because of its low recurrence. Here we reported a rare Bowen's disease case presented with multiple perianal lesions that were given surgical resection, but relapsed after 2 years. PMID- 26823843 TI - Racial disparity in placental pathology in the collaborative perinatal project. AB - OBJECTIVE: There is substantial disparity in perinatal outcomes between white and African-American women, but the underlying biological mechanisms are poorly understood. The placenta is the principal metabolic, respiratory, excretory, and endocrine organ of the fetus. We studied the association between maternal race and types and severity of placental pathology. METHODS: Using data from the U.S. Collaborative Perinatal Project (1959-1966), we studied 32,295 African-American and white women with singleton births. CPP pathologists conducted detailed placental examinations following a standard protocol with quality control procedures. Logistic regression modeling was used to test the association between race and placental pathology adjusting for potential confounders. RESULTS: Compared to white women, African-American women had a higher risk of fetal neutrophilic infiltration (adjusted odds ratio [aOR], 1.2; 95% confidence interval [CI], 1.0-1.4), and 1.5-fold higher risk of low placental weight (95% CI, 1.3-1.7). However, various placental vascular lesions were significantly less common in African-American women, including infarcts and thrombosis in the cut surface, villous infarcts in the intervillous space, emergence of stromal fibrosis and Langerhans layer in the terminal villi, old hemorrhage in the maternal surface, thrombosis in the intervillous space, and calcification throughout the cut surface (aOR ranging from 0.5 to 0.8). Similar patterns were observed in pregnancies with pregnancy associated hypertension, small-for gestational-age, and preterm birth. CONCLUSION: As compared with white women, African-American had higher prevalence of inflammatory lesions but lower prevalence of vascular lesions in placental pathology. PMID- 26823844 TI - COMT Val158Met polymorphism is associated with blood pressure and lipid levels in general families of Bama longevous area in China. AB - To see the possible relationship between COMT Val158Met polymorphism and blood pressure (BP) and serum lipid levels and its putative role in human longevity, we genotyped COMT Val158Met (rs4680) by PCR-RFLP for members from Bama long-lived families (BLF, n = 1538), Bama non-long-lived families (BNLF, n = 600), Pingguo (a county outside Bama region) long-lived families (PLF, n = 538) and Pingguo non long-lived families (PNLF, n = 403) after anthropometric measures were collected and serum lipid levels were detected. The distribution of genotypes and alleles among four family groups was significantly different (all P < 0.01), with GA/AA genotype and minor allele A presenting more frequently in Bama population than Pingguo Population (P < 0.01). The systolic blood pressure (SBP), pulse pressure (PP), total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) levels of GG genotype carriers were dramatically higher than non-GG carriers in BNLF (P < 0.05); the SBP and PP levels of GG carriers were lower (P < 0.05) while TC, LDL-C level were higher (P < 0.01) than that of non-GG carriers in PLF; no difference in blood pressure and lipids were observed between genotypes in BLF and PNLF (P > 0.05). Correlation analyses revealed that COMT Val158Met was mainly correlated negatively with SBP, diastolic blood pressure (DBP) and LDL-C in BNLF and negatively with TC level in BLF, BNLF and PLF. These data suggest that COMT Val158Met polymorphism may have more impact on the modulation of BP and lipid profiles in the average families than in the long lived families in Bama region. The association between this SNP and other phenotypes (e.g. cognition) and its roles in the longevity in Bama area thus warrant further investigation. PMID- 26823845 TI - Prognostic value of ERCC1 and ERCC2 gene polymorphisms in patients with gastric cancer receiving platinum-based chemotherapy. AB - We conducted a prospective study to analyze whether ERCC1 rs11615 and rs3212986 and ERCC2 rs13181 and rs1799793 gene polymorphisms could serve as potential biomarkers for the prognosis of gastric cancer. A total of 228 patients with pathologically proven gastric cancer and receiving platinum-based chemotherapy were recruited from our hospital between October 2009 and October 2011. The ERCC1 rs11615 and rs3212986 and ERCC2 rs13181 and rs1799793 polymorphisms were genotyped using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Conditional logistic regression analysis revealed that patients carrying the CA and AA genotypes of ERCC1 rs3212986 polymorphism showed a poorer response to chemotherapy compared to the CC genotype (CA vs. CC: OR = 0.28, 95% CI = 0.06-0.98, P = 0.04; AA vs. CC: OR = 0.49, 95% CI = 0.06 0.98, P = 0.01). Moreover, the CA+AA genotype of ERCC1 rs3212986 polymorphism showed a significantly poorer response to chemotherapy (CA+AA vs. CC: OR = 0.49, 95% CI = 0.27-0.90). Patients with the AA genotype of ERCC1 rs3212986 polymorphism had a longer overall survival time when compared with the CC genotype (34.91 months vs. 51.19 months, log-rank P = 0.003). The AA genotype of ERCC1 rs3212986 polymorphism in gastric cancer patients was correlated with a higher risk of death from varying causes by the Cox proportional hazards model, compared to the CC genotype (HR = 6.19, 95% CI = 1.42-30.60). In conclusion, the ERCC1 rs3212986 polymorphism was found to influence the response to chemotherapy and overall survival of gastric cancer patients. PMID- 26823846 TI - Immunohistochemistry is highly sensitive and specific for detecting the BRAF V600E mutation in papillary thyroid carcinoma. AB - The V600E mutation in the B-type Raf kinase (BRAF) gene is a common genetic change in cases of papillary thyroid carcinoma (PTC) that appears to play a key role in the development and progression of this disease. We sought to assess the sensitivity and specificity of immunohistochemical detection of this mutation with a V600E mutated BRAF antibody in a Chinese PTC cohort. In this study, we used fully automated immunohistochemistry (IHC) assay with a BRAF V600E (VE1) mouse monoclonal primary antibody to screen for the BRAF V600E mutation in 556 cases of PTC. Moreover, to verify the IHC staining results, real-time PCR was applied to detect this mutation in the same patient cohort. Among the 556 cases in the examined primary PTC cohort, 414 (74.5%) cases and 419 (75.4%) cases were positive for the BRAF V600E mutation by IHC staining and by real-time PCR, respectively. The real-time PCR results indicated that the sensitivity and specificity of IHC staining for the BRAF V600E mutation were 98.8% and 100%, respectively. The BRAF V600E mutation was common among Chinese patients with primary PTC, and was strongly correlated with older patient age and the conventional subtype of PTC but was not associated with parameters of clinicopathological aggressiveness. The fully automated IHC is a reliable technique that can serve as an alternative to molecular biological approaches for the routine detection of the BRAF V600E mutation in PTC patients. PMID- 26823847 TI - Association of angiotensin-converting enzyme gene polymorphisms with Crohn's disease in a Chinese Han population. AB - OBJECTIVE: To investigate whether Angiotensin-converting enzyme (ACE) gene polymorphisms alter the susceptibility of a Chinese Han population to Crohn's disease (CD). METHODS: Blood samples were collected from patients with CD and from healthy control subjects for analyzing SNP rs4291 (promoter, A262T), SNP rs4343 (exon 16, A11860G), and rs4646994 (intron 16, Alu insertion/deletion). Allele and genotype frequencies were compared, and pairwise linkage disequilibrium and haplotypes were analyzed in patients with CD. RESULTS: Both rs4343 A/G and rs4646994 I/D allele frequencies differed significantly between patients with CD and control subjects (rs4343: OR=1.438, 95% CI=1.099-1.882, P=0.008; rs4646994: OR=1.559, 95% CI=1.191-2.039, P=0.001). There were also significant associations between the risk of CD and both rs4343 AA/(AG+GG) and rs4646994 II/(ID+DD) genotype frequencies (P=0.039 and P=0.019). The frequency of the G-D haplotype was significantly lower in patients with CD than control subjects (31.7% vs. 40.4%, P=0.010). CONCLUSIONS: The results suggest that ACE rs4343G and rs4646994D alleles protect against CD, while rs4343AA and the I allele in the dominant genetic model are risk alleles for CD. The association between the G-D haplotype and CD was significant, suggesting a protective role in the pathogenesis of CD. PMID- 26823848 TI - Expression of Nemo-like kinase was increased and negatively correlated with the expression of TCF4 in lung cancers. AB - Nemo-like kinase (NLK), as a mitogen activated protein kinase (MAPK)-like kinase, is involved in the development of several human cancers. In this study, we explored the expression of NLK in lung squamous cell carcinoma (SCC) and adenocarcinoma tissues, and investigated the associations among NLK, beta catenin, T-cell factor 4 (TCF4), and the clinicopathological factors of lung cancers. The expressions of NLK, beta-catenin, TCF4 were examined in 109 cases of lung cancers using immunohistochemistry method. The expression of NLK was observed in the nuclei of lung cancer tissues, and was significantly higher in lung cancer tissues than that in corresponding normal lung tissues (t = 21.636, n = 109, P < 0.001). The high expression of NLK was found in 45 cases of lung SCCs (45/49, 91.84%), which was much more than that in adenocarcinomas (38/60, 63.33%) (P = 0.001). Furthermore, the high expression of NLK was negatively correlated with TCF4 expression and positively correlated with the membranous expression of beta-catenin. In conclusion, the present study demonstrated that the expression of NLK was localized in nucleus and significantly increased in lung cancers. The expression of NLK was negatively correlated with TCF4 expression and positively correlated with beta-catenin membranous expression in lung cancers. PMID- 26823850 TI - Expression of galectin-9 mRNA in hepatocellular carcinoma. AB - Liver cancer, with a very high prevalence, is one of the most common causes of death worldwide. Galectin-9, a semi-galactoside-binding protein, was demonstrated to be involved in the formation and metastasis processes of tumors such as breast cancer, and has significant impact on the development and prognosis of tumor. In this study, 90 cases of liver cancer patients who had liver cancer resection surgery treatment, were selected. Samples of liver cancer tissues and cancer adjacent tissues from the surgery resection of liver cancer patients, which also confirmed by pathology after operation as specimens, were obtained to detect the expression level of Galectin-9 mRNA. The comparing results showed that there were significant differences between the expression of Galectin-9 mRNA in cancer adjacent tissues and that in cancer tissues (P < 0.05), in terms of pathology differentiation, TNM, and recurrence transfer aspects. However, there were no obvious correlations with gender, age, the size of tumor, and HBsAg. The expression of Galectin-9 mRNA has a close relationship with pathological differentiation, TNM, and recurrence metastasis. Our data presented here provide theoretical basis for new target of liver cancer diagnosis as well as potential prognosis. PMID- 26823849 TI - Expression of eag1 channel associated with the aggressive clinicopathological features and subtype of breast cancer. AB - BACKGROUNDS: Expression of eag1 channel (Eag1) is associated with cell malignant transformation, tumor cell metastasis and poor prognosis of the patient. This study aimed at examining whether expression of the Eag1 associated with aggressive clinicopathological feature and the molecular subtype of breast cancer. MATERIALS AND METHODS: 109 patients who received breast cancer operation during January 2009 to December 2010 in Chinese-Japanese Friendship Hospital of Jilin University were recruited. We investigated the association of the Eag1 with clinicopathological features and molecular subtype of in triple negative breast cancer (TNBC) by univariate or multivariate analysis in a cross-section study. RESULTS: The positive rate of Eag1 was 18.5% higher in TNBC compared with non triple negative breast cancer (Non-TNBC) (P = 0.012, OR = 2.83, 95% CI = 2.16 3.47). Compared with the Eag1 negative group, the expression of Eag1 was linked to the larger tumor size (P = 0.002), advanced TNM stage (P = 0.029), high proportion of positive lymph node (87.6% vs. 65%, P = 0.014) and invasive ductal carcinoma (91% vs. 75%, P = 0.046). CONCLUSIONS: The expression of Eag1 may be partially explained the aggressive behavior of TNBC in the breast cancer tissue. PMID- 26823851 TI - Effects of simvastatin on the expression of inducible NOS in acute lung injury in septic rats. AB - BACKGROUND: The available evidence suggests that simvastatin plays a beneficial role in lung injury. In addition, statins have been shown to inhibit the activity of inducible nitric oxide synthase (iNOS). The aim of the present study was to investigate the effects of simvastatin on iNOS expression based on a lipopolysaccharide (LPS)-induced septic rat model. METHODS: Thirty-six rats were randomly divided into 3 groups (control group, sepsis group and simvastatin group). A rat model of sepsis was established with LPS. The simvastatin group was pre-treated with simvastatin, whereas the control and sepsis groups were treated with saline before LPS treatment. LPS was injected into the rats in the simvastatin and sepsis groups, while as a negative control, the control group received saline alone. The oxygenation index, expression levels of iNOS and IL-6, and pathological integral of lung injury were analyzed to evaluate the effect of simvastatin on septic rats. RESULTS: Compared with the septic group, significant decreases in the oxygenation index and expression level of iNOS were observed in the simvastatin group. Furthermore, simvastatin treatment resulted in a significant decrease in iNOS levels and the pathological integral of lung injury score in septic rats. CONCLUSION: Simvastatin can relieve acute lung injury induced by sepsis in rats. Decreasing iNOS levels may contribute to the protective role of simvastatin in lung injury. PMID- 26823852 TI - CA724 is a novel factor for predicting the unresectability in pancreatic adenocarcinoma. AB - This study aimed to assess the relationship between serum CA724 levels and the unresectability of pancreatic adenocarcinoma. A total of 302 patients with pancreatic adenocarcinoma were analyzed for the potential association between serum CA724 levels and the unresectability of pancreatic adenocarcinoma. Serum CA724 levels in patients with unresectable pancreatic adenocarcinoma were remarkably higher than those with resectable pancreatic adenocarcinoma (P < 0.001). Patients with elevated serum CA724 levels exhibited a 12.27-fold higher risk of unresectability than those with normal serum CA724 levels after adjusting for age, sex, and tumor location (95% CI = 5.28-28.51, P < 0.001). The analysis of receiver operating characteristics demonstrated that CA724 had superior predictive value to other tumor markers (AUC was 0.77 +/- 0.03, 0.65 +/- 0.04, and 0.62 +/- 0.04 for CA724, CA125, and CA199, respectively). CA724 appeared to be a better predictor of unresectability than CA199 and CA125. PMID- 26823853 TI - Association between CTLA-4 rs231775 polymorphism and hepatocellular carcinoma susceptibility. AB - AIMS: Our study aimed to investigate the association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) rs231775 polymorphism with hepatocellular carcinoma (HCC) susceptibility. METHODS: Genotypes distribution of the control was tested by Hardy-Weinberg Equilibrium (HWE). CTLA-4 rs231775 polymorphism was analyzed in 80 patients with HCC and 78 healthy controls by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method, and the expression level of CTLA-4 in the serum of all subjects was detected using enzyme linked immunosorbent assay (ELISA) kit. Odd ratio (OR) with 95% confidence interval (CI) were calculated by chi-squared test to determine the correlation of CTLA-4 rs231775 polymorphism and the risk of HCC. RESULTS: The genotypes frequencies of the control group were in accordance with HWE. The frequencies of genotype AA and allele A in CTLA-4 rs231775 polymorphism were significantly higher in cases than the control group (AA vs. GG: OR=2.81, P=0.043; A vs. G: OR=1.63, P=0.022). Meanwhile, the expression level of CTLA-4 was remarkably higher in cases compared with the controls. The association analysis indicated that AA genotype carriers exhibited highest level of CTLA-4 (P<0.01). CONCLUSIONS: The genotype AA and allele A of CTLA-4 rs231775 polymorphism may have negative effects on HCC by modifying the expression and functions of CTLA-4. PMID- 26823854 TI - The role of MBL2 gene polymorphism in sepsis incidence. AB - AIM: This case-control study was aimed to explore the role of mannose-binding lectin 2 (MBL2) gene rs1800450 polymorphism (codon 54 A/B, G230A) in the development of sepsis in Han Chinese. METHODS: MBL2 rs1800450 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). MBL serum level was detected by enzyme-linked immunosorbent assay (ELISA). Associations between rs1800450 and sepsis susceptibility was detected by Chi-square test and represented by odds ratios (ORs) and 95% confidence intervals (CIs). Correlation of rs1800450 genotypes and MBL serum level was assessed using t test. RESULT: Variant A allele frequency was significantly observed in cases than that in controls, indicating a significant association with the susceptibility of sepsis (OR = 1.979, 95% CI = 1.200-3.262). GA genotype also relate to the onset of sepsis (OR = 2.090, 95% CI = 1.163-3.753). MBL serum concentrations were significantly different between case and control groups (P<0.001). Meanwhile, variant allele carriers had lower serum level compared with wild homozygous (P<0.001). CONCLUSION: Variant A allele in MBL2 gene rs1800450 polymorphism might increase the risk of sepsis via decrease the MBL serum level. PMID- 26823855 TI - Correlation between microRNA-421 expression level and prognosis of gastric cancer. AB - The expression of microRNA-421 (miR-421) is significantly elevated in gastric carcinoma cells, thus may play an important role in tumor occurrence. This study thus aimed to further illustrate the correlation between miR-421 expression level and the progression and prognosis of gastric carcinoma. A total of 96 gastric carcinoma tissue samples were quantified for miR-421 expression level using quantitative PCR (qPCR) method. Kaplan-Meier survival curve was further deployed to analyze the postoperative survival of all patients. No significant correlation existed between miR-421 level and general information of patients such as age, sex, tumor size, location, invasion depth, TNM stage, differentiation stage and metastasis. However, miR-421 was significantly up-regulated in those tumors with lymph node metastasis (P<0.05), while those tumors with no lymph node metastasis had normal miR-421 level as those in control group (P>0.05). These results suggested the correlation between miR-421 up-regulation and lymph node metastasis. Those patients with high miR-421 expression had significantly shorter survival time compared to normal miR-421 patients (median: 37.34 months vs. 54.23 months, P<0.01), suggesting the correlation between miR-421 expression and prognosis of gastric cancer. MiR-421 level is correlated with lymph node metastasis and prognosis of gastric carcinoma, and is worth for further investigations. PMID- 26823856 TI - Expression of CD11c+HLA-DR+dendritic cells and related cytokines in the follicular fluid might be related to pathogenesis of ovarian hyperstimulation syndrome. AB - OBJECTIVE: To explore the expressions of CD11c+HLA-DR+dentritic cells in the follicular fluid of patients with OHSS and their significances. SUBJECTS: 100 individuals. TREATMENT: embryos were observed. The distribution of dentritic cells in follicular fluid and the levels of IL-10, IL-12, IL-18 and IL-23 in follicular fluid were detected. METHODS: There were ovarian hyperstimulation syndrome (OHSS) group and control group in this study. The OHSS group consisted of 50 patients with OHSS and the control group consisted of 50 patients who underwent in vitro fertilization-embryo transfer (IVF-ET) only due to male factors. The statuses of embryos were compared between the two groups. The distribution of dentritic cells in follicular fluid was determined with flow cytometry, and the levels of IL-10, IL-12, IL-18 and IL-23 in follicular fluid were detected with enzyme-linked immunosorbent assay (ELISA) in all patients. RESULTS: The two-pronuclear (2PN) fertility rate, high-quality embryo rate and available embryo rate were all significantly lower in OHSS group than in control group (all P<0.05). The number of CD11c+HLA-DR+dentritic cells (P<0.05) and the levels of IL-10, IL-12, IL-18 and IL-23 were all significantly higher in OHSS group than in control group (all P<0.01). CONCLUSION: The follicular fluid of the patients with OHSS is in an inflammatory status, the inflammatory status may be involved in OHSS and the microenvironment of follicular fluid may affects oocyte quality and embryo development. PMID- 26823857 TI - Decreased expression of long non-coding RNA MEG3 acts as a potential predictor biomarker in progression and poor prognosis of osteosarcoma. AB - INTRODUCTION: Long non-coding RNA MEG3 (lncRNA MEG3) has been showed to involve in a variety of cancers. However, the association between lncRNA MEG3 expression level and the prognosis of osteosarcoma is still unclear. METHODS: The expression levels of lncRNA MEG3 in osteosarcoma tissues and adjacent non-tumor tissues were detected using quantitative real-time PCR (qRT-PCR). Differences in patient survival were determined using the Kaplan-Meier method and a log-rank test. A Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values. RESULTS: Our findings showed that expression of lncRNA MEG3 was clearly lower in osteosarcoma tissues compared with adjacent non tumor tissues. The expression of lncRNA MEG3 was associated with clinical stage and distant metastasis (P<0.05). Kaplan-Meier analysis showed that patients with low lncRNA MEG3 expression had a shorter overall survival (log-rank test, P<0.05). Furthermore, multivariate analysis revealed that decreased expression of lncRNA MEG3, advanced clinical stage and distant metastasis were all independent predictors to overall survival of osteosarcoma patients. CONCLUSIONS: Downregulation of lncRNA MEG3 was associated with poor overall survival of osteosarcoma. LncRNA MEG3 could be a useful biomarker for progression and prognosis of osteosarcoma. PMID- 26823858 TI - A collision tumor of esophagus. AB - The collision tumor is defined by Meyer as that arisen from the accidental meeting and eventual intermingling of two independent neoplasms, which is quite rare. Most of them occur in the junction of different epithelial types of tissue such as oral cavity, esophagogastric junction, anorectaljunction and cervix, while collision tumors occurring in the liver, gallbladder, pancreatic, urinary bladder also have been reported. Here we present a case of 55-year-old Chinese man diagnosed as a collision tumor composed of leiomyosarcoma and squamous cell carcinoma (SqCC) in the lower third part of esophagus with 6 years survival after surgery and radiotherapy. PMID- 26823859 TI - B-cell lymphoma 2 rs17757541 C>G polymorphism was associated with an increased risk of coronary artery disease in a Chinese population. AB - The goal of our study was to evaluate the genetic effects of sixteen single nucleotide polymorphisms (SNPs) in apoptosis-related genes on the development of coronary artery disease (CAD) through a case-control study. A total of 1979 individuals, including 826 CAD cases (aged 67.27 +/- 10.26 years) and 1153 non CAD controls (aged 59.13 +/- 10.51 years), were enrolled into the study. The genotypes were determined using a custom-by-design 48-Plex SNPscanTM Kit. The results showed that the BCL2 rs17757541 C>G polymorphism was associated with increased risk of CAD in homozygote comparison and recessive genetic model. However, no association between the other fifteen SNPs and CAD risk was observed. Stratified analyses indicated a significantly increased risk of CAD associated with the BCL2 rs17757541 C>G polymorphism among males and younger patients. Therefore, the results indicated that there is a close correlation between the BCL2 rs17757541 C>G polymorphism and CAD, which suggests that this SNP site should be further studied as a potential biomarker for CAD. PMID- 26823860 TI - Association between BRAF and RAS mutations, and RET rearrangements and the clinical features of papillary thyroid cancer. AB - OBJECTIVE: To evaluate the significance of BRAF (V600E) and Ras mutations, and RET rearrangements in papillary thyroid cancer (PTC) in the South central region of China. METHODS: We included patients from Union hospital's pathology archive diagnosed with PTC and meeting the criteria for BRAF mutation, RAS mutation, and RET rearrangement testing. Medical records were analyzed for BRAF and RAS mutation status, RET rearrangements (positive or negative), and a list of standardized clinicopathologic features. RESULTS: Positive BRAF mutation was found to be significantly associated with age and extrathyroidal extension (P=0.011 and P=0.013, respectively). However, there was no significant association between BRAF mutation and sex, tumor size, histological subtype, multifocality, or accompanying nodular goiter and Hashimoto's. On the other hand, none of these characteristics of PTC were been found to be associated with RAS mutation. Additionally, the frequency of RET rearrangements was higher in patients <=45 years old than that in patients >45 years old. CONCLUSIONS: We demonstrated that the BRAF (V600E) mutation slightly correlated with the clinicopathological characteristics of PTC in the Han population. Furthermore, neither RAS mutation nor RET rearrangements were found to be associated with the clinicopathological characteristics of PTCs. Our work provides useful information on somatic mutations to predict the risk of PTC in different ethnic groups. PMID- 26823861 TI - CD40 -1C>T polymorphism and the risk of lung cancer in a Chinese population. AB - BACKGROUND: The co-stimulatory molecule CD40 plays an important role in anti tumor responses by promoting cytotoxic T lymphocyte (CTL) activity and differentiation of helper T cells. Growing evidence suggests that single nucleotide polymorphisms (SNPs) in CD40 are associated with the susceptibility to cancer. This study investigated the association between the CD40 -1C/T SNP (rs1883832) and lung cancer in a Chinese population. METHODS: We conducted a hospital-based case-control study including 105 lung cancer patients and 109 healthy control subjects. The -1C/T SNP in CD40 was genotyped by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), and its association with lung cancer susceptibility was evaluated. RESULTS: The distribution of the genotypes of CD40-1C/T was significantly different between lung cancer patients and controls. The frequency of the TT genotype (adjusted P = 0.017; overall risk [OR] = 2.94; 95% confidence interval [CI] = 1.21-7.13) and TT/CT genotype (adjusted P = 0.020; OR = 1.95; 95% CI = 1.11-3.43) were significantly higher in lung cancer patients than that in controls. When the cases were categorized by tumor histology, the TT genotype was associated with a significantly increased risk of squamous cell carcinoma (adjusted OR = 6.53; 95% CI = 1.97-21.61; P = 0.002). CONCLUSION: Our findings suggest that the CD40 -1C/T SNP (rs1883832) is correlated with the susceptibility to lung cancer in Chinese, and the TT genotype may further increase the risk of lung cancer. PMID- 26823862 TI - Interleukin-10 -1082A/G polymorphism is associated with the development of acute pancreatitis in a Chinese population. AB - We conducted a case-control study to investigate the association between IL-10 gene polymorphism (-1082A/G, -819T/C, and -592A/C) and risk of acute pancreatitis in a Chinese population. A total of 240 patients with proven acute pancreatitis and 240 control subjects were collected between May 2012 and January 2015. Genotyping of the IL-10-1082A/G, -819T/C, and -592A/C gene polymorphisms was conducted by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. By univariate logistic regression analysis, patients with acute pancreatitis were more likely to have higher BMI (OR=2.12, 95% CI=1.45-3.12; P<0.001) and have a habit of alcohol drinking (OR=2.01, 95% CI=1.37-2.95; P<0.001). There were significant differences in the genotype distributions of IL-10-1082A/G between patients with acute pancreatitis and control subjects (chi(2)=9.97, P=0.007). By multiple logistic regression analysis, we found that individuals with the GG genotype of IL-10-1082A/G were associated with an increased risk of acute pancreatitis when compared with the AA genotype (OR=2.32, 95% CI=1.20-4.59; P=0.007). In dominant and recessive models, the IL-10-1082A/G gene polymorphism was significantly correlated with an elevated risk of acute pancreatitis, and the adjusted Ors (95% CI) were 1.50 (1.03-2.20) and 1.99 (1.06-3.79), respectively. However, no significant different was found between IL-10-819T/C and -592A/C gene polymorphisms and susceptibility to acute pancreatitis. In conclusion, we suggest that IL-10-1082A/G gene polymorphisms contribute to the development of acute pancreatitis in codominant, dominant and recessive models. PMID- 26823863 TI - Predictive role of miR-146a rs2910164 (C>G), miR-149 rs2292832 (T>C), miR-196a2 rs11614913 (T>C) and miR-499 rs3746444 (T>C) in the development of hepatocellular carcinoma. AB - We conducted a case-control study to evaluate the association of miR-146a rs2910164 (C>G), miR-149 rs2292832 (T>C), miR-196a2 rs11614913 (T>C) and miR-499 rs3746444 (T>C) polymorphisms with the risk of hepatocellular carcinoma. A total of 274 patients with HCC were collected between January 2013 and December 2014. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was taken to determine the polymorphism of miR-146a C>G, miR-149 T>C, miR-196a2 T>C and miR-499 T>C. By comparing with control groups, patients with HCC were more likely to be males (OR=2.01, 95% CI=1.38-2.95), have older age (OR=1.52, 95% CI=1.09-2.13), have a history of alcohol drinking (OR=2.09, 95% CI=1.49-2.93), and be infected with HBV (OR=32.98, 95% CI=19.70-55.46) and HCV (OR=56.26, 95% CI=23.28-152.98) infection. By conditional regression analysis, individuals carrying the TC and CC genotypes of miR-196a2 T>C were found to be associated with an elevated risk of HCC compared to the TT genotype, and the adjusted odds ratio were 1.50 (1.03-2.17) and 2.86 (1.60-5.16), respectively. Moreover, the TC+CC genotype was correlated with an increased risk of HCC (OR=1.69, 95% CI=1.19 2.41) compared to the wide-type genotype. In conclusion, our results suggested that miR-196a2 T>C polymorphism is associated with HCC risk in Chinese population. PMID- 26823864 TI - Changes in intrinsic subtype of breast cancer during tumor progression in the same patient. AB - Hormone receptor (HR), human epidermal growth factor receptor 2 (HER2) and Ki67 are important prognostic factors and key variables in classification of the intrinsic subtype, which is essential for choice of adjuvant therapy in breast cancer management. There has been earlier reports that instability of hormonal and HER2 status during progression of tumor. However, breast cancer treatment guidelines recently recommended using the intrinsic subtype that is determined by four immunohistochemical (IHC) assays, estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki67. The purpose of study was to investigate whether the intrinsic subtype changes during the tumor progression from ductal carcinoma in situ (DCIS) to lymph node metastasis. The study included 90 patients with breast cancer in Korea University Guro Hospital, between 1992 and 2008. All individuals had DCIS, invasive carcinoma and lymph node metastasis lesion. IHC staining for ER, PR, HER2 and Ki67 as well as SISH assay for HER2 gene amplification was done with following standard method. Overall 25% of breast cancer changed their intrinsic phenotype during progression. Study demonstrated that a subset of breast cancers can change their intrinsic subtype during cancer progression. These changes have an impact on patient prognosis and management, because each breast cancer subtype has their own differently optimized treatment options according to St. Gallen and NCCN guideline. PMID- 26823865 TI - Association of GSTs polymorphisms with risk of gestational diabetes mellitus. AB - We conducted a case-control study to investigate the association between GSTM1, GSTT1 and GSTP1 IIe105Val polymorphisms and development of gestational diabetes mellitus in a Chinese population. A total of 320 patients with gestational diabetes mellitus and 358 pregnancy subjects were consecutively collected between January 2013 and December 2014. Genotyping for detection of GSTM1, GSTT1 and GSTP1 IIe105Val was conducted by using PCR-RFLP (polymerase chain reaction restriction fragment length polymorphisms) method. By Fisher's exact test, we found that the genotype distributions of GSTP1 IIe105Val were in line with the Hardy-Weinberg equilibrium in control subjects (P=0.57). By Chi-square test, we found significant differences in the genotype distributions of GSTM1 (chi(2)=11.49, P=0.001) and GSTT1 (chi(2)=18.50, P<0.001). Using unconditional logistic analysis, individuals carrying the null genotypes of GSTM1 and GSTT1 were associated with an increased risk of gestational diabetes mellitus when compared with the present genotype, and the adjusted Ors (95% CI) were 1.71 (1.24 2.36) and 2.00 (1.44-2.79), respectively. However, the GSTP1 IIe105Val polymorphism was not associated with an elevated risk of gestational diabetes mellitus. In conclusion, we suggest that the GSTM1 null genotype and GSTT1 null genotype are correlated with an increased risk of gestational diabetes mellitus in a Chinese population. PMID- 26823866 TI - Association of PTEN gene polymorphisms with liver cancer risk. AB - OBJECTIVE: To find out if there are any relationship between three single nucleotide polymorphisms (SNPs) of phosphatase and tensin homolog (PTEN) gene (rs1234213, rs1234220, and rs2299939) and the susceptibility of liver cancer. METHODS: Genotypes of the three SNPs in the PTEN gene were achieved utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Comparison of genotypes and alleles distribution differences between the case and the control subjects was accomplished with chi(2) test. The analysis of linkage disequilibrium (LD) and haplotypes of the three SNPs was performed using SHEsis software. We adopted odds ratios (ORs) with 95% confidence intervals (95% CIs) to show the relative risk of liver cancer. RESULTS: TC genotype and C allele of rs1234220 polymorphism showed much more frequently in cases than in controls, reflecting that the TC genotype and the C allele may be linked to the increased risk of liver cancer (OR=2.225, 95% CI=1.178-4.204; OR=1.941, 95% CI=1.124 3.351). Rs2299939 polymorphism showed an opposite result that the GT genotype probably reduce the risk of liver cancer (OR=0.483, 95% CI=0.259-0.900). Statistical significance was not found in the distribution differences of the genotypes of rs1234213 between two groups. LD and haplotype analysis results of the three SNPs showed that the T-C-G haplotype frequency was much higher in cases than in healthy objects, which proved that the T-C-G haplotype might be a susceptibility haplotype for liver cancer (OR=3.750, 95% CI=1.396-10.077). CONCLUSIONS: PTEN gene polymorphisms might relate to liver cancer risk. PMID- 26823867 TI - TNF-alpha and IL10 polymorphisms interaction increases the risk of ankylosing spondylitis in Chinese Han population. AB - AIMS: The target of this article was to reveal the role of tumor necrosis factors alpha (TNF-alpha) and Interleukin-10 (IL10) gene polymorphisms in ankylosing spondylitis (AS) development and explore the interaction between these two gene polymorphisms. METHODS: The genotyping of gene polymorphims was conducted using ABI Taqman assay method in 84 AS patients and 92 healthy people. Hardy-Weinberg equilibrium (HWE) was checked in the control group and the genotypes and alleles difference were compared with chi(2) test. Odds ratio (OR) with 95% confidence interval (CI) was calculated to identify the strength of association between gene polymorphism and disease. Meanwhile, multifactor dimensionality reduction (MDR) method was used to analysis the interaction between gene polymorphisms. RESULTS: The genotypes CG+CC of the minor allele in IL10 rs1878672 in cases was obviously higher frequency than the controls (P=0.03) and the minor allele C was also associated with the increased risk of AS, compared with G allele (OR=2.05, 95% CI=1.08-3.89). Rs3024490 in IL10 also showed a significant correlation to the onset risk of AS (GG vs. TT: OR=3.03, 95% CI=1.04-8.87; G vs. T: OR=1.70, 95% CI=1.08-2.68). What's more, there was the interaction between TNF-alpha rs3093662 and IL10 rs3021094, rs3024490 polymorphisms in AS. CONCLUSIONS: IL10 rs1878672 and rs3024490 polymorphisms obviously increase the susceptibility to AS, but not TNF-alpha rs3093662. Both IL10 and TNF-alpha polymorphisms may affect the onset of AS. PMID- 26823868 TI - Genetic analysis of TNFST15 variants in ankylosing spondylitis. AB - AIMS: The purpose of this study was to explore the role of TNF-like ligand 1A (TL1A) gene (TNFST15) polymorphisms (rs3810936, rs7848647, and rs6478109) in the generation of ankylosing spondylitis (AS). METHODS: Polymerase chain reaction (PCR) and sequencing were used to conduct the genotyping of TNFSF15 polymorphisms in 113 AS patients and 120 healthy persons as the case and control groups. The frequencies comparison was performed by chi-square or t test between the two groups. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated to represent the correlation between TNFSF15 polymorphism and AS. Besides, genotypes distribution of the former in controls was checked by Hardy-Weinberg equilibrium (HWE). RESULTS: There was statistically significant difference in AS patients and controls based on family history. Among TNFSF15 polymorphisms, only TT genotype frequency of rs3810936 in cases was obviously high, compared with the controls (P=0.04), the results indicated that TT was a high-risk genotype (OR=2.31, 95% CI=1.03-5.20). However, both of rs6478109, rs7848647 polymorphisms didn't show any association with AS. CONCLUSION: Rs3810936 of TNFSF15 were related to the risk of AS and we should pay more attention to the role of TNFSF15 polymorphisms in the pathogenesis of AS in the future. PMID- 26823869 TI - Investigation on the association between inerleukin-10 -592C/A, 819C/T and 1082A/G gene polymorphisms and development of diabetic nephrophathy. AB - We conducted a case-control study to investigate the association between interleukin (IL)-10-592C/A, -819C/T and -1082A/G polymorphisms and susceptibility to diabetic nephropathy. A hospital-based case-control study was taken in our study. A total of 172 patients with proven type 2 diabetes mellitus and 344 controls were recruited from the First Affiliated Hospital of Xinxiang Medical University between March 2012 and October 2014. Genotyping of IL-10 -592C/A, 819C/T and -1082A/G polymorphisms was done by done by PCR-RFLP methods. By the chi(2) test, the distributions of the GG, GA and AA genotypes in IL-10 -1082A/G were significantly different between patients with diabetic nephropathy and control subjects (chi(2) = 8.09, P = 0.02). By conditional logistic regression analysis, we found that the AA genotype of IL-10 -1082A/G was associated with an elevated risk of diabetic nephropathy compared to the GG genotype in codominant model, and the adjusted OR (95% CI) was 2.38 (1.23-4.57). In dominant model, the GA+AA genotype was associated with a significantly increased risk of diabetic nephropathy compared to the GG genotype in dominant model (OR = 1.47, 95% CI = 1.05-2.16). In recessive model, the AA genotype could influence the susceptibility to diabetic nephropathy when compared with the GG+GA in recessive model (OR = 2.08, 95% CI = 1.12-3.85). In conclusion, we suggested that IL-10 1082A/G gene polymorphism was correlated with development of diabetic nephropathy, but no association was observed between IL-10 -819T/C and -592A/C and risk of diabetic nephropathy. PMID- 26823870 TI - EFEMP1 rs3791679 polymorphism was associated with susceptibility to glioma. AB - We conducted a case-control study in a Chinese population, and investigated the association between four SNPs (rs3791679, rs1346786, rs1344733 and rs727878) in EFEMP1 and development of glioma. A case-control study was taken in the present study. The rs3791679, rs1346786, rs1344733 and rs727878 gene polymorphisms were analyzed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. A total of 159 patients with glioma and 364 controls were collected between July 2012 and June 2014. By unconditional logistic regression analysis, we found that individuals carrying the AA genotype and GA+AA genotype were associated with development of glioma when compared with the GG genotype, and the adjusted ORs (95% CI) were 2.13 (1.15-3.90) and 1.55 (1.04-2.32), respectively. However, we did not find that rs1346786, rs1344733 and rs727878 were significantly associated with development of glioma. Moreover, we found that the GA+AA genotype of rs3791679 was associations with a heavy increased risk of glioma in patients who have family history of cancers, and the OR (95% CI) was 6.81 (1.17-48.06). The results of our study suggested an association between the rs3791679 polymorphism and an elevated risk of glioma, especially in those with family history of glioma. PMID- 26823871 TI - Interleukin-16 rs4778889 polymorphism contributes to the development of renal cell cancer in a Chinese population. AB - We conducted a case-control study to assess the role of IL-16 rs4778889, rs11556218 and rs8034928 polymorphisms in the development of RCC. This case control study included 181 patients with RCC and 278 control patients. The genotyping of IL-16 rs4778889, rs11556218 and rs8034928 polymorphisms were performed using polymerase chain reaction (PCR) combined with restriction fragment length polymorphism analysis. By chi(2) test, we found that patients with RCC were more likely to suffer from hypertension (chi(2) = 9.06, P = 0.003) and diabetes (chi(2) = 7.91, P = 0.005). By unconditional logistic regression analysis, the CC genotype of rs4778889 was associated with an increased risk of RCC compared to TT genotype, and the adjusted OR (95% CI) was 3.58 (1.59-8.31). In dominant model and recessive model, we found the rs4778889 polymorphisms were associated with an elevated increased risk of RCC, and the adjusted ORs (95% CI) were 1.64 (1.10-2.43) and 3.07 (1.40-6.98), respectively. We found that rs4778889 polymorphism had interaction with hypertension (OR = 2.44, 95% CI = 1.01-6.00) and diabetes (OR = 6.91, 95% CI = 1.44-37.05) in the risk of RCC. In conclusion, the results of our study suggested an association between the IL-16 rs4778889 polymorphism and an elevated risk of RCC. PMID- 26823872 TI - Evaluation of peripheral lymphadenopathy with excisional biopsy: six-year experience. AB - BACKGROUND: Lymphadenopathy (LAP) may be the first symptom of many diseases. We aimed to investigate peripheral LAP results taken by excisional biopsy. METHODS: Histopathological examination of 185 lymph node biopsy specimens were evaluated between January 2009 and April 2015 in Istanbul Private Ekin Pathology Laboratory, retrospectively. RESULTS: The average age of patients ranged from 1 to 86 was 41.01 +/- 20.62 years. 87 of were female, 98 of male. 62 (33.5%) of excisional biopsy materials were benign lesions and 123 (66.5%) of malignant. Benign lesions were consisted of reactive hyperplasia, cat-scratch disease, toxoplasmosis, necrotizing/non-necrotizing granulomatous. Of these patients, 40 had nodes with reactive hyperplasia (15 female/25 male, mean age: 27.35 y), 14 had necrotizing granulomatous disease (9 female/5 male, mean age: 39.86 y), 2 non necrotizing granulomatous disease (1 female/1 male mean age: 43 y), 4 had cat scratch disease (1 female/3 male mean age: 54.25 y), 1 toxoplasmosis (26 y, female), 1 Kikuchi disease (25 y, female). In the evaluation of malign lesions; 38 were Hodgkin lymphoma (HL) (20.5%, 17 female/21 male, mean age: 34.89 y) 77 had non-Hodgkin lymphoma (NHL) (41.6%, 37 female/40 male, mean age: 52.26 y), 8 metastasis (4.3%, 5 female/3 male, mean age: 53.5 y). Reactive LAP observed most common in cervical region, NHL in axillary-abdomen-inguinal-mediastinum and HL in the supraclavicular region. CONCLUSION: Excisional biopsy can be applied safely with minimal morbidity and mortality and a gold standard diagnostic method for LAP. Although LAP is mostly related with benign lesions, malignancy should be kept in mind in differential diagnosis. PMID- 26823873 TI - ABCB1 polymorphisms associated with osteonecrosis of the femeral head. AB - AIMS: This case-control study was conducted to investigate the relation of ATP binding cassette subfamily B member 1 (ABCB1) C1236T and C3435T polymorphisms and non-traumatic osteonecrosis of the femeral head (ONFH). METHODS: We gathered 113 ONFH patients and 116 controls in the study. The polymorphisms of ABCB1 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. Odds ratio (OR) with 95% confidence interval (CI) were adopted to analyze the correlation between ABCB1 polymorphisms and ONFH. RESULTS: In the study, we found that the frequency of C3435T TT genotype was much lower in case group, compared with that of controls (17.7% vs. 23.3%). Moreover, OR and 95% CI values indicated that C3435T TT genotype served as a protective factor for ONFH (OR=0.34, 95% CI=0.15-0.75). Meanwhile, the risk for the T allele carriers was much lower than C allele (OR=0.60, 95% CI=0.42-0.87). However, C1236T polymorphism showed no significant effects on the pathogenesis of ONFH. In the haplotype analysis, T-T haplotype appeared to be an inhibitor for ONFH (OR=0.45, 95% CI=0.23-0.87). CONCLUSIONS: Based on the results, ABCB1 polymorphisms were associated with the risk for ONFH. PMID- 26823874 TI - Association between EGFR polymorphisms and the risk of lung cancer. AB - TARGET: The study aimed to investigate the role of epidermal growth factor receptor (EGFR) rs6965469 and rs763317 polymorphisms in the occurrence and development of lung cancer. METHODS: We used polymerase chain reaction-ligation detection reaction (PCR-LDR) method to detect the genotypes of EGFR rs6965469 and rs763317 polymorphisms and the data were analyzed by GeneMapper software. Odds ratios (ORs) with 95% confidence intervals (CIs) was calculated by chi(2) test to estimate the significance difference of genotype and allele frequencies in case and control groups. ORs and 95% CIs were adjusted by logistic regression analysis with age, gender, drinking and smoking. The genotypes distributions of control group were tested by Hardy-Weinberg equilibrium (HWE). RESULTS: The genotypes frequencies of controls for rs6965469 and rs763317 polymorphims were consistent with HWE. The distribution of rs6965469 TT genotype in two groups was significantly different (P<0.05) and TT genotype was associated with an increased risk of lung cancer (OR=6.92, 95% CI=1.33-36.00). AA genotype and A allele of rs763317 were also the susceptible factors of lung cancer. Individuals with AA genotype or A allele were more likely to suffer lung cancer (AA vs. GG: OR=7.20, 95% CI=1.33-39.07; A vs. G: OR=2.61, 95% CI=1.04-6.59). CONCLUSIONS: The EGFR rs6965469 and rs763317 polymorphisms may be risk factors for lung cancer. PMID- 26823875 TI - Correlation of interactions between NOS3 polymorphisms and oxygen therapy with retinopathy of prematurity susceptibility. AB - AIM: This study was aimed to detect the correlation of nitric oxide synthase 3 (NOS3) gene polymorphisms (T-786C and G894T) and retinopathy of prematurity (ROP) susceptibility. Interaction between NOS3 gene polymorphisms and the duration of oxygen therapy was also explored in ROP babies. METHODS: Genotypes of NOS3 gene polymorphisms were genotyped by MassArray method. Hardy-Weinberg equilibrium (HWE) was used to calculate the representativeness of the cases and controls. Crossover analysis was utilized to explore the gene environment interactions. Relative risk of ROP was presented by odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs). RESULTS: Among the subject features, oxygen therapy had obvious difference between case and control groups (P<0.05). There existed significant association between-786C allele and ROP susceptibility (P=0.049, OR=0.669, 95% CI=0.447-0.999). Genotypes of T-786C polymorphism and genotypes and alleles of G894T polymorphism did not related to the susceptibility of ROP. Interactions were existed between NOS3 gene polymorphisms and oxygen therapy duration. When the duration of oxygen therapy was less than 17 days, both -786CC genotype and 894GT genotype were correlated with ROP susceptibility (P=0.020, OR=0.115, 95% CI=0.014-0.960; P=0.011, OR=0.294, 95% CI=0.100-0.784). CONCLUSION: -786C allele might have a protective effect for ROP. Interactions of 786CC and 894GT genotype with oxygen therapy duration (less than 17 days) were both protection factors of ROP. PMID- 26823876 TI - PIK3CA polymorphisms associated with susceptibility to hepatocellular carcinoma. AB - PURPOSE: Our study was carried out to explore the relationship of PIK3CA rs17849071 and rs17849079 polymorphisms with the susceptibility to hepatocellular carcinoma (HCC) in Chinese Han population. METHODS: 150 HCC patients and 152 healthy individuals were recruited in the case and control groups respectively. The genotypes of PIK3CA rs17849071 and rs17849079 polymorphisms were detected with polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP) method. The linkage disequilibrium and haplotypes were analyzed with Haploview software. Differences in frequencies of genotypes, alleles, and haplotypes between the case and control groups were checked with chi(2) test. The controls were matched with the cases in age and gender. The relative risk of HCC was represented by odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: Significant difference in frequencies of GG genotype and G allele in PIK3CA rs17849071 polymorphism existed between the two groups (P=0.040; P=0.028), indicating that rs17849071 was closely related to the increased risk of HCC (OR=2.919, 95% CI=1.007-8.460; OR=1.642, 95% CI=1.051-2.564). Furthermore, TT genotype also significantly increased the susceptibility to HCC (OR=3.438, 95% CI=1.050-11.250) and so was T allele (OR=1.521, 95% CI=1.052-2.199). The haplotype analysisshowed that G-T haplotypes were higher in cases than that of controls (P=0.030), which suggested that G-T might be a susceptible haplotype to HCC. CONCLUSIONS: The PIK3CA rs17849071 and rs17849079 polymorphisms may increase the risk of HCC either independently or synergistically. PMID- 26823877 TI - Short-term effects of splenectomy on serum fibrosis indexes in liver cirrhosis patients. AB - OBJECTIVE: To determine the changing patterns of 4 liver fibrosis markers pre and post splenectomy (combined with pericardial devascularization [PCDV]) and to examine the short-term effects of splenectomy on liver fibrosis. METHODS: Four liver fibrosis markers of 39 liver cirrhosis patients were examined pre, immediately post, 2 days post, and 1 week post (15 cases) splenectomy (combined with PCDV). RESULTS: The laminin (LN) level decreased immediately post surgery compared with the preoperative LN level (P < 0.05). The type IV collagen level decreased immediately post surgery compared with that pre surgery (P < 0.05), it significantly increased (P < 0.05) 2 days post surgery and significantly decreased 1 week post surgery (P < 0.05). Hyaluronic acid and the procollagen III N-terminal peptide levels increased significantly 2 days post surgery compared with that pre and immediately post surgery, they significantly decreased 1 week post surgery compared to 2 days post surgery (P < 0.05). CONCLUSIONS: In the short-term, the 4 liver fibrosis markers and the FibroScans post splenectomy showed characteristic changes, splenectomy may transiently initiate the degradation process of liver fibrosis. PMID- 26823878 TI - Association between HRH4 polymorphisms and ankylosing spondylitis susceptibility. AB - TARGET: The purpose of the study was to investigate the association between the histamine H4 receptor (HRH4) polymorphisms and the susceptibility to ankylosing spondylitis (AS). METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to analyze the HRH4 rs8088140 and rs657132 polymorphisms. Linkage disequilibrium and haplotype analyses were conducted with Haploview software. The genotypes distributions of HRH4 polymorphisms in the control group were tested by Hardy-Weinberg equilibrium (HWE), allele, genotype and haplotype frequencies between the cases and control groups were compared by chi(2) test. The controls were matched with cases by age and gender. The relative risk of AS with HRH4 polymorphisms was represented by odds ratio (OR) with 95% confidence interval (CI) calculated by chi(2) test. RESULTS: The genotypes distributions of HRH4 rs8088140, rs657132 polymorphisms in controls conformed to HWE. The frequency of rs657132 AA genotype in the case group was obviously higher than that in the control group (P=0.040), and so was the A allele (OR=2.572, 95% CI=1.475-4.486, P=0.022). The frequency differences of A-A haplotype between two groups had statistical significance (P=0.011, OR=2.071, 95% CI=1.172-3.660) through haplotype analysis, indicating A-A might be the susceptible haplotype to AS. CONCLUSION: The AA genotypes of HRH4 rs657132 polymorphism may be the susceptible factors for AS, and rs657132 plays a role in generation of AS. In addition, A-A haplotype in rs8088140-rs657132 is also increased the risk of AS. PMID- 26823879 TI - Promoter polymorphism T-786C, 894G->T at exon 7 of endothelial nitric oxide synthase gene are associated with risk of osteoporosis in Sichuan region male residents. AB - OBJECTIVE: To investigate the association between genetic polymorphism of T-786C in promoter region, 894G->T at exon 7 of endothelial nitric oxide synthase (eNOS) gene and osteoporosis (OP) disease. METHOD: The genotypes of 350 patients with osteoporosis and 350 healthy controls were detected by polymerase chain reaction (PCR) and DNA sequencing. The allele ratios and genotype distributions in the patients and controls were assessed using the Pearson chi(2)-test. Odds ratios (OR) with two tailed P-values and 95% confidence intervals (CI) were calculated as a measure of the association of the eNOS genotypes with OP. RESULT: the C allele distribution frequency of T-786C eNOS gene in OP group (8.5%) was significantly higher than that in control group (3.9%), relative risk (OR) of OP associated with the CC genotype was 2.68 (95% CI, 0.92 to 1.37). The T allele frequency of 894G->T at exon 7 in eNOS gene in OP group (11.5%) was also significantly higher than that in control group (5.2%), OR of OP associated with the TT genotype was 2.60 (all P<0.05). CONCLUSION: The analysis results indicated that both T-786C in promoter region and 894G->T at exon 7 of eNOS gene might be genetic predisposal factors of OP, these polymorphisms may be independently or synergic with other loci to have an impact on the incidence of OP. PMID- 26823880 TI - Homocysteine, endothelin-1 and nitric oxide in patients with hypertensive disorders complicating pregnancy. AB - OBJECTIVE: To investigate the change of level of serum homocysteine (Hcy), endothelin-1 (ET-1) and nitric oxide (NO) and clinical significance in patients with HDCP. METHODS: Two hundred and thirty nine patients with HDCP (137 patients with mild preeclampsia, 102 patients with severe preeclampsia) who were hospitalized between June 2012 and June 2015 and 200 normal pregnancy women in outpatient department were enrolled in our study were divided into HDCP group and control group. Serum Hcy concentration was measured by enzymatic cycling assay. ET-1 concentration was measured by enzyme linked immunosorbent assay. And no concentration was measured by nitrate reductase assay. RESULTS: Serum Hcy and ET 1 in HDCP group were significantly higher as compared to control group (P<0.05). Level of serum NO in HDCP group was significantly lower than in the control group (P<0.05). Level of serum Hcy and ET-1 in mild and severe preeclampsia group were significantly higher as compared to control group, respectively (P<0.05). Level of serum NO in mild and severe preeclampsia group were significantly lower than in the control group' respectively (P<0.05). Level of serum Hcy and ET-1 in severe preeclampsia group were significantly higher as compared to mild preclampsia group (P<0.05). Level of serum NO in severe preeclampsia group were significantly lower than in mild preeclampsia group (P<0.05). Spearman rank correlation analysis showed that level of serum Hcy and ET-1 was positively correlated with severity of diseases (r=0.689, 0.718, P<0.05). Level of serum NO was negatively correlated with severity of diseases (r=-0.702, P<0.05). CONCLUSION: Serum Hcy, ET-1 and NO were associated with pathogenesis of HDCP. Comprehensively measurement of them could effectively evaluate the incidence and progress of HDCP. PMID- 26823881 TI - Characterization of the abnormal lipid profile in Chinese patients with psoriasis. AB - Psoriasis is a chronic inflammatory skin disease that has been associated with abnormal lipid metabolism. To characterize the lipid profile in Chinese, 86 patients with psoriasis and 84 healthy control subjects were assessed. Compared with healthy controls, the fasting serum values of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) were lower in the patient group. Compared with vulgaris psoriasis, special types of psoriasis had even lower levels of HDL C and ApoA-I. Considering the severity of psoriasis, the level of ApoA-I and HDL C were also the only two serum lipid parameters decreased in the mild group compared to those in controls. In the moderate and the severe group, the values of TC, LDL-C, HDL-C and ApoA-I were all decreased compared to healthy control group. Further analysis indicated that the values of HDL-C and ApoA-I were significantly lower in the severe group compared to the moderate group. Correlation analysis indicated that the levels of HDL-C but not ApoA-I was negatively associated with the severity of the disease. Interestingly, when psoriasis was improved by treatment, the serum levels of TG, TC, HDL-C and ApoA-I were increased from the pre-treatment values. We conclude that abnormalities in serum lipid metabolism may play an important role in the pathogenesis of Chinese patients with psoriasis. PMID- 26823882 TI - Skull metastasis from follicular thyroid carcinoma: report of three cases and review of literature. AB - Three patients' medical history, clinical manifestation, imaging characteristic, therapy and prognosis of calvaria metastasis from follicular thyroid carcinoma (FTC) in our hospital were retrospectively analyzed by reviewing medical literature. In case one, the tumor in frontal bone and fossa orbital was total resected, no further treatment was performed, the patient gave up on therapy and died of extensive metastasis at 22 months after the initial operation. In case two, the tumor in parietal and occipital bone was total resected, the subtotal resection of bilateral thyroid gland and isthmus was performed and combined with therapy of Levothyroxine and (131)I radio-iodine therapy, no evidence of tumor recurrence at 30 months after the primary operation. In case three, the tumor in occipital bone was gross total resected, total resection of bilateral thyroid gland and clearance of lymph node was performed after two months, adjunctive therapy with Levothyroxine, (131)I radio-iodine and skull radiotherapy, no evidence of tumor recurrence at 21 months after the primary operation. Correct diagnosis of calvaria metastasis from FTC preoperative is difficult because it's rarity, patients can survive for years after synthetic therapy including total resection of metastatic tumor, radical operation of thyroid carcinoma, adjunctive therapy of Levothyroxine, (131)I radio-iodine and skull radiotherapy. PMID- 26823883 TI - Acute promyelocytic leukemia with cryptic t(15;17) on isochromosome 17: a case report and review of literature. AB - Acute Promyelocytic Leukemia (APL) is one of the most curable leukemia which shows great sensitivity to all-trans retinoic acid (ATRA) although a small number of the patients present poor prognosis and short survival. Isochromosome 17 in APL which usually bears an additional copy of RARA/PML fusion gene is considered to be a negative factor on its prognosis. Cryptic t(15;17) on i(17q) leads to an extra copy of PML/RARA rather than RARA/PML which may confer a worse prognosis. We describe here a rare APL case with complex chromosomal abnormality including isochromosome 17 bearing cryptic t(15;17) showing poor outcome. The patient lacks a classic t(15;17) and fluorescence in situ hybridization (FISH) presents 2 PML/RARA fusion signals on both long arms of the isochromosome. The patient also acquired a secondary mutation at relapse when the initial karyotype was already a complex karyotype involving chromosome 13, 17 and 22 at the same time. The poor response of this patient to traditional chemotherapy like ATRA and novel therapy like arsenic trioxide (ATO) suggests that early auto-hematological stem cell transplantation may be the choice of APL with isochromosome 17 especially with cryptic t(15;17) on i(17q). We are the first to show a clear history and evidence of FISH of these kind of cases. A small summary of cases with cryptic t(15;17) on isochromosome 17 is also made. PMID- 26823884 TI - Peroxidase-positive Auer bodies in plasma cells in multiple myeloma: a case report. AB - Reports of clinical cases with Auer bodies in the plasma cells in multiple myeloma (MM) are rare; however, most of those reported contain peroxidase (POX) negative Auer bodies rather than the POX-positive Auer bodies observed in myeloid progenitors, indicating differences in their chemical properties. Furthermore, the cases with POX-positive Auer bodies similar to those observed in myeloid cells are extremely rare in non-myeloid cells. Here, we report the clinical features, laboratory investigations, diagnosis and treatment of a case of MM with POX-positive Auer bodies in plasma cells and review related the literature to advance the prognostic evaluation, diagnosis and treatment of similar cases. PMID- 26823885 TI - Bronchogenic cyst in the hepatogastric ligament masquerading as an esophageal mesenchymal tumor: a case report. AB - Lesions occur in hepatogastric gap is common, but most of these lesions are from stomach, lower esophagus and pancreas lesions extending or transferring to the gap. Lesions occurred in the hepatogastric ligament are rare, especially bronchogenic cysts in the hepatogastric ligament. So far, there were no relevant cases reported. Here, we report a case of bronchogenic cyst in the hepatogastric ligament that masquerading as an esophageal mesenchymal tumor. A 24-year-old young man presented with abdominal bloating was diagnosed as esophageal mesenchymal tumor in previous hospital by gastroscopy, endoscopic ultrasonography (EUS) and computed tomography (CT) examination. For the sake of endoscopic submucosal dissection (ESD), the man was transferred to our hospital. During surgery, we found no lesions in lower esophagus, but external pressure ridge lesions in the distal esophagus right side wall. Then laparoscopic surgery and pathology confirmed as bronchogenic cyst in the hepatogastric ligament. We report what is, to the best of our knowledge, the first case of a bronchogenic cyst in the hepatogastric ligament masquerading as an esophageal mesenchymal tumor. PMID- 26823886 TI - Langerhans cell sarcoma arising from the root of tongue: a rare case. AB - Langerhans cell sarcoma (LCS), a rare malignant disease with markedly malignant cytological features and poor outcome, originates from Langerhans cells and most commonly affects the lymph nodes, skin, and bone. This paper presents the case of a 58-year-old female with LCS at the root of her tongue, with neither local recurrence nor distant metastasis observed during 47 months of follow up following radiotherapy for more than one month after complete tumor resection. Histological and immunophenotypic tests revealed that the malignant tumor cells were positive for S-100 protein, CD1a, and LCA, and partially positive for CD3epsilon. By contrast, the tumor cells were negative for langenin, CD30, HMB45, PCK, CK5/6, and P63. Their Ki-67proliferation index ranged from 30% to 40%. This neoplasm was diagnosed as LCS according to the classification of WHO2008. This work is the first report on LCS arising from the root of tongue. This rare case may serve as a reference for future clinical studies. PMID- 26823887 TI - Alveolar rhabdomyosarcoma of nasopharynx and paranasal sinuses with metastasis to breast in a middle-aged woman: a case report and literature review. AB - Alveolar rhabdomyosarcoma (ARMS) is a common soft tissue tumor in children which can rarely metastasize to the breast in adults. Here we report the rare case of a 42-year-old Asian woman, who was diagnosed with ARMS of the nasopharynx and paranasal sinuses, and got a complete remission (CR) after surgery and chemoradiotherapy. Then the patient relapsed in the unilateral breast seventeen months later. Histology and immunohistochemistry of the primary sites and the breast lesions, combined with FISH, have been performed to confirm the diagnosis of metastatic alveolar rhabdomyosarcoma. With a rational therapeutic regimen of surgery, chemotherapy and radiotherapy, the patient has got a complete remission again. PMID- 26823888 TI - Primary Sjogren's syndrome accompanied by pleural effusion: a case report and literature review. AB - Sjogren's syndrome (SS) is a systemic autoimmune disease characterized by the infiltration of lymphocytes in exocrine glands, specifically the salivary and lacrimal glands, resulting in the typical symptoms of xerophthalmia and xerostomia. SS may be accompanied by pleural effusion when the lung is involved, but this occurrence has been reported in only 10 cases in the literature. We report the case of a 42 year-old woman with severe bilateral pleural effusion for eight years. Primary Sjogren's Syndrome was finally diagnosed based on the presence of xerophthalmia and xerostomia, biopsy of the minor salivary glands, and positive anti-SS-A antibody in the serum and pleural effusion. Biopsy of the parietal pleura through video-assisted thoracoscopy revealed infiltration of lymphocytes. The patient had a long history of pleural effusion without clear etiology. Malignant disease was first suspected because of abnormal density lesion on the left lung and malignant cells found on cytology, but PET-CT revealed no malignant lesion. Examinations did not support infection, malignant tumor, pulmonary sarcoidosis, or other connective tissue diseases. This data could be useful for the future study of pleural effusion in SS. PMID- 26823889 TI - Epithelioid inflammatory myofibroblastic sarcoma treated with ALK inhibitor: a case report and review of literature. AB - Epithelioid inflammatory myofibroblastic sarcoma is extremely rare and belongs to a variant of inflammatory myofibrobalstic tumor with aggressive clinical course. We describe a case of a 22 years old man presented with an abdominal huge tumor. Microscopically, the neoplasm cells were rounded and epithelioid in shape. Abundant interstitial edema and less myxoid stroma were also present together with an inflammatory infiltrate. Fluorescence in situ hybridization revealed that ALK gene presented mutation. After surgery the patient received chemotherapy with an anaplastic lymphoma kinase (ALK) inhibitor, crizotinib. The patient continues to be alive with disease for 16 months and has no recurrence. Although EIMS has a poor prognosis, this is the few successful case with sustained response of targeted therapy. PMID- 26823890 TI - A case of matrix-producing metaplastic carcinoma of the breast exhibiting similarities to pleomorphic adenoma on fine-needle aspiration cytology. AB - The distinction between matrix-producing metaplastic carcinoma (MPMC) and pleomorphic adenoma (PA) is sometimes unclear in breast pathology, especially on core needle biopsy. Herein, we presented a 66-year-old woman with MPMC of the breast that looked like PA on fine-needle aspiration cytology (FNAC). On FNAC, the appearance of abundant myxoid matrix along with cellular clusters composed of monotonous cellular populations looked like salivary PA, which we were familiar with owing to the frequency in routine pathological practice. Thus, the possibility of breast PA, the counterpart of salivary PA, was considered. However, the tumor location was different from where breast PA frequently occurs, i.e. the retroareolar region. Therefore, we eliminated the possibility of breast PA and avoided the erroneous cytological diagnosis. It is should be kept in mind that MPMC can look like PA on FNAC. PMID- 26823891 TI - KRAS mutation-positive bronchial surface epithelium (BSE)-type lung adenocarcinoma with strong expression of TTF-1: a case providing a further insight as for the role of TTF-1 in the oncogenesis. AB - Bronchial surface epithelium (BSE)-type lung adenocarcinoma is a subtype of non terminal respiratory unit (TRU)-type lung adenocarcinoma originating in the bronchial surface epithelium. However, there are few known cases of BSE-type adenocarcinoma with marked expression of thyroid transcription factor-1 (TTF-1). This paper describes a very rare case of KRAS mutation-positive BSE-type adenocarcinoma that exhibited strong expression of TTF-1 that was putatively involved in oncogenesis. An 84-year-old woman, a never smoker, was referred to our hospital because of an abnormal chest radiograph. Chest computed tomography (CT) showed a solid mass lesion, 15 mm * 10 mm, with a relatively smooth margin in the left upper lobe. The patient underwent partial resection of the left upper lobe for strongly suspected lung cancer with a clinical stage of cT1aN0M0. Histopathological findings showed continuous migration of papillary, hyperplastic, atypical columnar tumor cells originating from normal bronchial surface epithelium, leading to a diagnosis of BSE-type adenocarcinoma. TTF-1 was strongly expressed in almost 100% of the tumor cells, which tested positive for the KRAS mutation. TTF-1 has recently attracted attention as an oncogene, and it is purportedly involved in the carcinogenesis and survival of lung adenocarcinoma cells. There is typically an inverse correlation between the respective expressions of KRAS and TTF-1, but in the present study, they appeared simultaneously and were both putatively involved as oncogenic driver alterations. This case is important in that it sheds some light on the largely unknown pathogenic mechanism of BSE-type adenocarcinoma. PMID- 26823892 TI - Invasive urothelial carcinoma with chordoid features of the ureter: a rare entity and review of literature. AB - Invasive urothelial carcinoma (UC) is characterized by some histologic variants that can sometimes lead to diagnostic difficulty. In addition to those described by the World Health Organization. Recently invasive urothelial carcinoma with chordoid features (UCC) has been described as a distinct entity and there are relatively few reported cases in the English-language literature. To date 13 cases of UCC have been reported in 2 case series, respectively in 2009 and 2015. We report the 14(th) case in an 80-year-old female, and to the best of our knowledge this is the second case report of UCC in the ureter. She was admitted to our hospital with macroscopic haematuria and unspecific left lower abdominal pain. Computed tomography scan revealed a soft tissue nodule in the middle of the left ureter. The left nephroureterectomy was performed. Morphologically, 85% areas had acellular myxoid stroma was associated with the neoplastic cells. The neoplastic cells had scant eosinophilic cytoplasm and were arranged into cords closely mimicking chordoma or extraskeletal myxoid chondrosarcoma. 15% areas was typical invasive urothelial carcinoma, and focal areas had transition phenomenon between them. Immunohistochemically, the tumor cells were positive for CK, 34betaE12 and p63, but were negative for S100, AFP, CD34, Syn and CgA. The final histopathological diagnosis was UCC of the ureter. PMID- 26823893 TI - Hepatocellular carcinoma in nonalcoholic fatty liver disease mimicking benign hemangioma: two case reports and literature review. AB - OBJECTIVE: To study the clinical features of nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC). METHODS: The clinical manifestations, imaging features, pathological subtypes and treatment outcome of two cases with NAFLD-associated HCC were analyzed. RESULTS: In these two cases, both were young, obese male patients, with contrast enhanced CT scan of hemangioma-like features. They had undergone surgical resection and both were reported as well-differentiated HCC pathologically. They were followed-up respectively up to 46 and 36 months post-operatively with no evidence of recurrence or metastasis. CONCLUSIONS: NAFLD-associated HCC has different radiological presentations from typical HCC. Incidental finding of any liver occupying lesions in NAFLD patients should raise immediate clinical attention. PMID- 26823894 TI - Benign fibrous histiocytoma of the fronto-temporo-parietal region: a case report and review of the literature. AB - Primary benign fibrous histiocytoma (BFH) at the skull is extremely rare. Here we report a case of a 22-year-old man presented with a 1-year history of progressive enlargement subcutaneous mass on the right side of the fronto-temporo-parietal region without symptoms. The tumor was radical resected through craniotomy and the bone defect was repaired by pre-plasticity titanium mesh. Histopathologic examination confirmed a benign fibrous histiocytoma, and no signs of tumor recurrence were detected at 3-year follow-up. PMID- 26823895 TI - A giant pelvic malignant schwannoma: a case report and literature review. AB - Schwannomas are usually benign tumors that arise from well-differentiated Schwann cells. They rarely occur in the retroperitoneum. Here, we present a case of a 60 year-old man with a giant retroperitoneal pelvic mass. Imageological diagnosis suggested a large heterogeneous mass of 16 cm in diameter located in the abdominopelvic retroperitoneum. Complete intralesional enucleation was achieved without any adjacent organs injury except a severe bleeding which was ceased as we applied the bilateral inferior vesical artery embolization. Final histopathological result showed the tumor was a low malignant Schwannoma. The patient's symptoms were greatly improved after operation. Unfortunately, a local recurrence was detected at the six-month follow-up appointment with consequent losing to follow up. PMID- 26823896 TI - Diverse proportion in composite pheochromocytoma-ganglioneuroma may induce varied clinical symptom: comparison of two cases. AB - Composite pheochromocytoma-ganglioneuroma is extremely rare. We described two cases of composite pheochromocytomas in the adrenal medullar. Case 1 was a 70 year-old male presenting with lower abdominal pain and normal blood electrolytes. Case 2 was a 48-year-old female with palpitation and back tenderness. Biochemical investigations showed hypocalcium, hypokalemia and high level of vma. The histological images and the immunohistochemical staining demonstrated the two cases composed of pheochromocytoma and ganglioneuromoma components. Ganglioneuroma component in case 2 accounted for more proportion than that in case 1. We speculated that the varied clinical symptoms were related with the diverse proportions in composite pheochromocytome-ganglioneuroma. PMID- 26823897 TI - Metaplastic thymoma with myasthenia gravis presumably caused by an accumulation of intratumoral immature T cells: a case report. AB - Among human neoplasms, thymomas are well known for their association with paraneoplastic autoimmune diseases such as myasthenia gravis. However, regarding rare metaplastic thymoma, only one case of an association with myasthenia gravis has been reported. Here, we present the second case of a 44-year-old woman with metaplastic thymoma associated with myasthenia gravis. In metaplastic thymoma, intratumoral terminal deoxynucleotidyl transferase-positive T-cells (immature T cells) are generally scarce, while they were abundant in the present case. We believe that these immature T-cells could be related to the occurrence of myasthenia gravis. PMID- 26823898 TI - Concurrent tamoxifen-related Mullerian adenofibromas in uterus and ovary. AB - Tamoxifen is a widely used in anti-oestrogen treatment of breast cancer. Previous reports showed that tamoxifen is associated with proliferative endometrial lesions. We herein reported an unusual case of concurrent hyperplastic lesions in the uterine cavity and right ovary in a 45-year-old woman with tamoxifen therapy. Regular vaginal ultrasonography showed the progressive endometrial thickening and right ovary enlargement during the period of drug use. Both lesions in the uterine cavity and right ovary showed characteristics resembling that of Mullerian adenofibroma. There were also foci of endometriosis in her bilateral ovarian surfaces. We suggest that women taking tamoxifen with a known history of endometriosis should be followed with transvaginal ultrasonography periodically. PMID- 26823899 TI - A case of gastric adenocarcinoma metastasis to the esophagus possibly caused by gastroscopy or gastric reflux. AB - Recurrence after curative resection for gastric cancer is high, the pattern of recurrence include haematogenous metastasis, peritoneal metastasis, lymph node metastasis, and local recurrence, respectively. Here we report a case with local recurrence at the beginning, and subsequent metastasis to the esophagus three month following gastroscopy. Biopsy of the nodule in the upper esophagus was taken, pathology showed the adenocarcinoma of gastric origin. CT scanning showed no thickening of upper esophagus wall, suggesting there may not be intramural metastasis. The patient had proven gastroesophageal reflux, and the liner alignment of the lesion coexisted with the route of gastroscope insertion tube. Taken together, we suggest that the esophagus metastasis was most likely though implantation caused by gastroscopy or gastroesophageal reflux. PMID- 26823900 TI - Pulmonary arterial hypertension due to pulmonary vascular amyloid deposition in a patient with multiple myeloma. AB - Systemic amyloidosis is characterized by amyloid deposition throughout the body and subsequent dysfunction of various organs. Although pulmonary amyloidosis does occur, pulmonary hypertension (PH) caused by amyloidosis is extremely rare. In most of these cases, amyloid deposition occurred diffusely in alveolar septa, indicating that PH was due to lung disease and/or hypoxia. On the other hand, the mechanism of PH due to amyloid deposition in the pulmonary arteries has never been demonstrated. Here, we report the first case of PH due to amyloid deposition in pulmonary elastic arteries and muscular artery, which was complicated by multiple myeloma (MM). In the autopsy specimen of the patient, amyloid deposition was found mainly in the pulmonary arterial media, along with intimal thickening with luminal narrowing. PH thus appeared to be caused by marked decrease of pulmonary elasticity due to the amyloid deposition in the arterial media that resulted in stasis of the blood flow and subsequent luminal narrowing. Our present data demonstrates a new concept of PH caused by amyloidosis, namely, pulmonary arterial hypertension due to amyloidosis. PMID- 26823901 TI - ACTH-secreting pancreatic neuroendocrine carcinoma with ovarian and pelvic metastases causing Cushing's syndrome: a case report. AB - Adrenocorticotropin hormone (ACTH)-secreting pancreatic neuroendocrine carcinoma (NEC) with ovarian and pelvic metastases causing Cushing's syndrome is very rare and might be misdiagnosed. We describe a case of ACTH-secreting pancreatic poorly differentiated NEC developing bilateral ovarian and pelvic metastases. A 27-year old woman presented with thirst, polydipsia, fatigue and poorly controlled hyperglycemia. Laboratory and imaging investigations revealed hypokalemia, hyperglycaemia, ACTH-dependent hypercortisolemia and a 12-cm mass at the junction of body and tail of the pancreas with ovarian and pelvic nodules. The patient underwent partial pancreatectomy and splenectomy, uterectomy, bilateral oophorectomy, and excision of peritoneal nodules. Tumors in pancreas, ovaries and pelvis were diagnosed as poor-differentiated NEC. After 19-month chemotherapy, she developed pelvic metastasis. The tumor in our case is a large, poorly differentiated NEC secreting ACTH and causing CS, with ovarian metastases. To our knowledge, this new additional case of ACTH-secreting pancreatic NEC with ovarian metastases would add to the better understanding of this tumor. PMID- 26823902 TI - Glomus tumor of uncertain malignant potential of the lung: a case report and review of literature. AB - Glomus tumor is an uncommon tumor usually presenting in the dermis. Rarely, it occurred in visceral organs including stomach, liver and long. The majority of glomus tumors were benign. Herein, we present a case of glomus tumor located in the left lobe of the lung in a 49 year-old Chinese male. An irregular mass measuring 3 cm was detected by imaging examination because of his suffering from cough, dyspnea and chest pain. Histologically, the tumor is composed predominantly of sheets of ovoid to round cells with clear border, pale cytoplasm and fine granular chromatin. The mitotic count was less than 5 per 50 HPF. The tumor focally invaded the surrounding normal bronchial and alveolar tissue. Immunohistochemical staining showed that the cells were diffusely positive for SMA, caldesmon, and vimentin. The Ki-67 proliferation index was approximately 20%. Based on morphologic features and the immunohistochemical profile, the tumor was consistent with glomus tumor of uncertain malignant potential. PMID- 26823903 TI - Lobulated adenomyoepithelioma: a case report showing immunohistochemical profiles. AB - Lobulated adenomyoepithelioma of the breast is an extremely rare lesion, with hyperplasia of myoepithelial cells and glandular epithelial cells. We present a case of a 51-year-old woman with a small painless hard lump in each breast. The lesion in the left breast was an irregular solid mass, and the right breast showed a subareolar nodule with bloodstained nipple discharge. The final diagnosis was intraductal papillary carcinoma in the right breast and lobulated adenomyoepithelioma in the left breast. In the left breast lesion, histopathologic examination revealed multiple nodules composed of proliferative glandular epithelial cells and surrounding myoepithelial cells. Solid nests of clear or eosinophilic myoepithelial cells proliferated around compressed epithelial-lined space. Smaller satellite nodules were seen. Immunohistochemistry revealed myoepithelial cells were positive for P63, smooth muscle actin, calponin, 34betaE12, CK5/6 and CK14, while glandular epithelial cells were positive for AE1/AE3 and CK7. Lobulated adenomyoepithelioma has a high chance of recurrence and malignant degeneration due to inadequate excision. Therefore, understanding of the pathological morphology and accurate diagnosis is important for surgical planning. Moreover, close follow-up is recommended for patients with lobulated adenomyoepithelioma despite the lesion being reported as benign. PMID- 26823904 TI - Cardial leiomyosarcoma with multiple lesions involved: a case report. AB - BACKGROUND: Leiomyosarcoma of the heart is extremely rare and may involve many symptoms. The outcome is poor and the median survival is only 6 months. CASE PRESENTATION: A 43-years-old female patient complained of palpitation and dyspnea and was diagnosed as bilateral iliac vein-inferior vena cava-right atrium pulmonary masses. Pathological diagnosis was leiomyosarcoma of vascular origin and she survived for 12 months after surgery. CONCLUSION: According to the summarization of 30 vascular leiomyosarcoma cases with heart involved we can find that surgical resection is the basic treatment for cardiac leiomyosarcoma, and surgery combined with chemotherapy may be able to further prolong survival. PMID- 26823905 TI - Metastasis of breast cancer to renal cancer: report of a rare case. AB - Tumor-to-tumor metastasis (TTM) is a rare phenomenon. We present a case of an invasive ductal carcinoma (IDC) of the breast metastasizing to a clear cell renal cell carcinoma (RCC). Breast cancer (BC) metastasis to the RCC is rarely reported, especially in resected kidney tumor. In several cases reported, IDC was the exclusively histologic type of BC metastasized to RCC. It seems that the different molecular type of IDC doesn't affect the metastatic tendencies to RCC. TTM was an indicator of diffuse disease. For any patient with a history of breast cancer, especially with multi-organs metastasis, resection of kidney tumor should be carefully considered. PMID- 26823906 TI - Renal pelvis urothelial carcinoma of the upper moiety in complete right renal duplex: a case report. AB - Urothelial carcinoma (UC) originated from renal pelvis is the common tumor of the urinary system, however, neoplasia of the renal pelvis in duplex kidneys is extremely rare, especially in the complete renal and ureteral duplex cases. We present the first case of renal pelvis UC of the upper moiety in a complete right renal duplex. This male patient has bilateral complete renal and ureteral duplex. To the best of our knowledge, this is the first reported case of renal pelvis UC in a complete renal duplex system. After this experience we feel that the diagnosis of renal pelvis UC in duplex kidneys is not so easy, and once the diagnosis is determined, the whole renal duplex units and bladder cuff or ectopic orifice should be excised radically. PMID- 26823907 TI - Primary pleuropulmonary synovial sarcoma: a case report. AB - Pleuropulmonary synovial sarcoma (PPSS) is an extremely rare malignant tumor, which is increasingly recognized as a subtype of sarcoma with a distinctive chromosomal translocation specific to synovial sarcoma. It is often presents like any thoracic tumor with symptoms such as chest pain or cough. Here we report a case of PPSS in a 49-year-old woman presenting with cough, shortness of breath and chest pain. And who were found upon histologic examination of the resection specimen to have cystic primary pleuropulmonary synovial sarcoma. PMID- 26823908 TI - Multiple myeloma developing during long-term clinical course of refractory immune thrombocytopenic purpura: a case report and review of literature. AB - Immune thrombocytopenia (ITP) is an acquired, immune-mediated disease that is characterized by increased destruction of platelets by autoantibodies. Although the onset of the disease and clinical course are highly variable, the disease typically has a benign course. ITP associated with multiple myeloma (MM) has been rarely reported; it is even rarer for MM to develop during a long-term ITP (almost 20 years). Here, we first report on a case with a 20-year long clinical course of refractory ITP followed by newly diagnosed MM. PMID- 26823909 TI - Angiomatous lesion and delayed cyst formation after gamma knife surgery for intracranial meningioma: case report and review of literatures. AB - Gamma Knife has become a major therapeutic method for intracranial meningiomas, vascular malformations and schwannomas with exact effect. In recent years an increasing number of delayed complications after Gamma Knife surgery have been reported, such as secondary tumors, cystic changes or cyst formation. But angiomatous lesion and delayed cyst formation after Gamma Knife for intracranial lesion has rarely been reported. Here we report the first case of angiomatous lesion and delayed cyst formation following Gamma Knife for intracranial meningioma and discuss its pathogenesis. PMID- 26823910 TI - A pelvic cellular solitary fibrous tumor with multifocal expression of cytokeratin AE1/AE3. PMID- 26823911 TI - Genetic background and phenotypic heterogeneity of MELAS and maternally inherited diabetes and deafness. PMID- 26823912 TI - Aberrant promoter methylation of SH3GL2 gene in vulvar squamous cell carcinoma correlates with clinicopathological characteristics and HPV infection status. AB - OBJECTIVE: This study attempted to examine the methylation status of SH3GL2 gene in different types of human vulvar lesions and its correlation with clinicopathological parameters. METHODS: Immunohistochemical analysis was used to identify the expression status of SH3GL2 in vulvar squamous cell carcinoma (VSCC), vulvar intraepithelial neoplasia (VIN) and benign vulvar squamous epithelium tissues. Bisulfite genomic sequencing method was used to detect methylation status of the SH3GL2 gene. Clinicopathological correlation of the alterations was analysed by the chi-square tests. RESULTS: Immunohistochemical analysis showed expression of SH3GL2 in VSCC was significantly downregulated than that in VIN and normal vulvar tissues. In accordance with higher frequency of methylation status in SH3GL2, statistical analysis showed methylation status of SH3GL2 was closely related to tumor TNM stage (P=0.003), but not related to age, tumor volume, tumor differentiation, lymph node metastasis and VIN grade. High methylation status of SH3GL2 showed significant association with HPV infection status. CONCLUSIONS: Our results indicated that the methylation status of SH3GL2 gene was associated with the TNM staging and HPV infection status of VSCC, suggesting that it might play a synergistic role in the development of VSCC. PMID- 26823913 TI - Presence of ulceration, but not high risk zone location, correlates with unfavorable histopathological subtype in facial basal cell carcinoma. AB - BACKGROUND: Basal cell carcinoma (BCC) has been stratified into low- and high risk according to their propensity for local recurrence. Risk factors for recurrence include histologic subtype, anatomic location (i.e. H-zone of the face), horizontal diameter, and patient health status. OBJECTIVE: To assess if favorable (superficial, nodular, adenoid and trabecular) and unfavorable (infiltrative, morpheaform, micronodular, metatypical, basosquamous) histopathological subtypes of BCC do correlate with anatomic location on the face (facial high risk versus non-high risk zones). METHODS: Histopathological specimens of all facial BCCs, which were histopathologically diagnosed in the Pathology Department of Sisli Etfal Training Hospital, between the years 2008 and 2014 were retrospectively studied. Histopathological aggressive and non aggressive subtypes as well as the presence of ulceration were correlated with facial high-risk (i.e. H-zone) and low risk anatomical locations. RESULTS: Of 184 BCC of unfavorable subtypes, 101 cases were identified in facial high-risk anatomical region (H-zone) compared to 83 cases at non H-zone (P = 0.553). On the other hand the ulceration rate was significantly higher for unfavorable histological subtypes than in the favorable histopathological subtype group (P = 0.042). Regarding anatomic site, ulceration frequency was not significantly different for the H-versus non-high risk zones (P = 0.335). CONCLUSIONS: A correlation of unfavorable histopathological subtype of BCC and high-risk anatomical location (i.e. H-zone) was not observed in our study. Our results however confirmed a significantly higher rate of ulceration in the subgroup of aggressive histopathological BCC forms. Thus, factors other than histopathological subtype (such as narrow excision margin related to difficult surgical technique in H-zone, microcirculation, vasculature and host inflammatory response) may be responsible for the high recurrence rate in facial H-zone located BCCs. PMID- 26823914 TI - Effects of duloxetine on microRNA expression profile in frontal lobe and hippocampus in a mouse model of depression. AB - Depression is a major mood disorder affecting people worldwide. The posttranscriptional gene regulation mediated by microRNAs (miRNAs) which may have critical roles in the pathogenesis of depression. However, to date, little is known about the effects of the antidepressant drug duloxetine on miRNA expression profile in chronic unpredictable mild stress (CUMS)-induced depression model in mice. Healthy adult male Kunming mice were randomly divided into three groups: control group, model group and duloxetine group. Sucrose preference test and open field test were used to represent the behavioral change. MiRNAs levels in frontal lobe and hippocampus of mice were analyzed using miRNA microarrays assay. We observed that long-term treatment with duloxetine significantly ameliorated the CUMS procedure-induced sucrose preference decreases and mice treated with duloxetine demonstrated a reversal of the number of crossings, and rearings reduced by CUMS. A significant upregulation of miR-132 and miR-18a in hippocampus in the duloxetine treatment group compared with model group, whereas the levels of miR-134 and miR-124a were significantly downregulated. Furthermore, miR-18a showed significant upregulation in frontal lobe in the duloxetine treatment group relative to model group. Our data showed that miRNA expression profile in frontal lobe and hippocampus was affected by duloxetine in mice model of depression. The effect was especially pronounced in the hippocampus, suggesting that hippocampus might be the action site of duloxetine, which presumably worked by regulating the expression of miRNA levels. PMID- 26823915 TI - Differential proteomics analysis of mononuclear cells in cerebrospinal fluid of Parkinson's disease. AB - Parkinson's disease (PD) is one common neurodegenerative disease featured with degeneration of dopaminergic neurons in substantia nigra. Multiple factors participate in the pathogenesis and progression of PD. In this study, we investigated the proteomics profiles of mononuclear cells in cerebrospinal fluids from both PD patients and normal people, in order to explore the correlation between disease factors and PD. Cerebrospinal fluid samples were collected from both PD and normal people and were separated for mononuclear cells in vitro. Proteins were then extracted and separated by 2-dimensional gel electrophoresis. Proteins with differential expressions were identified by comparison to standard proteome expression profile map, followed by software and database analysis. In PD patients, there were 8 proteins with consistent expression profile and 16 proteins with differential expressions. Those differential proteins identified include cytoskeleton proteins (actin, myosin), signal transduction proteins (adenosine cyclase binding protein 1, calcium binding protein, talin) and anti oxidation factor (thioredoxin peroxide reductase). PD patients had differential protein expressional profiles in the mononuclear cells of cerebrospinal fluids compared to normal people, suggesting the potential involvement of cytoskeleton and signal transduction proteins in apoptosis of neuronal apoptosis and PD pathogenesis. PMID- 26823916 TI - Clinical significance and prognostic value of Nek2 protein expression in colon cancer. AB - OBJECTIVE: To determine the expression of NIMA-related kinase NEK2 and evaluate its clinical value in colon cancer. METHOD: Sixty specimens of colon cancer, 30 specimens of paracancerous colon tissues and 10 specimens of normal colon tissues conventionally resected in surgery at the Second Affiliated Hospital of Nantong University from February 2006 to February 2014 were collected. These tissues were detected for the expression of Nek2 using Western Blot and immunohistochemical staining. The relationship between Nek2 protein expression and the clinicopathology and prognosis of colon tissues was discussed. RESULTS: The expression level and positive expression rate of Nek2 protein in the colon cancer were obviously higher than that in the paracancerous tissues and normal colon tissues. They were also significantly higher in the paracancerous tissues than in the normal tissues (P<0.05). Statistical analysis revealed that Nek2 protein expression was not obviously correlated with gender, age and tumor size, but obviously correlated with degree of differentiation (P=0.008), TNM staging (P=0.000), lymph node metastasis (P=0.022) and tumor invasion (P=0.011). With the plotting of Kaplan-Meier survival curve, it could be seen that Nek2 protein expression was not significantly correlated with survival (P=0.0048). High Nek2 protein expression may be an independent risk factor for colon cancer (HR=0.227, 95% CI 0.101-0.510). CONCLUSION: High Nek2 protein expression reflects the malignant behavior of colon cancer. Playing important roles in the occurrence of colon cancer, Nek2 protein expression has diagnostic and prognostic value in colon cancer. PMID- 26823917 TI - Anti-N-methyl-D-aspartate receptor encephalitis with occult ovarian teratoma: a case report. AB - A 31-year-old female was admitted with headache, memory disturbance, abnormal behavior, incontinence, confusion, complex partial seizures, decreased oxygen saturation and increased temperature. Anti-NMDAR antibodies were positive in serum and cerebrospinal fluid. Subsequently, a regimen of immunotherapy that included intravenous immunoglobulins, methylprednisolone, plasma exchange and their combinations were used. But the treatment was ineffective. Though both transvaginal ultrasonography and abdominal CT scan contrast revealed left ovarian cyst, the patient had left oophorectomy. And during surgery we found a small cyst mass contained fat-like liquid with air in her left ovarian. Pathological examination demonstrated mature cystic teratoma accompanied with brain tissue. She has made gradual and steady improvement after surgery, but not fully recovery. By combining this case with previous studies of others, we further discuss the clinical characteristics, treatment and prognosis of the disease. PMID- 26823918 TI - Development of a new real-time PCR system for simultaneous detection of bacteria and fungi in pathological samples. AB - A novel system for simultaneous detection of pathogenic bacteria and fungi in pathological samples was developed using a real-time polymerase chain reaction (PCR) system. This system, designated the "multi-microbial real-time PCR", has the potential to simultaneously detect 68 bacterial and 9 fungal species in a 96 well plate format. All probe-primer sets were designed to produce amplicons smaller than 210 bp using formalin-fixed paraffin-embedded samples as input. The specificity and sensitivity of each probe-primer set were tested against DNA extracted from pure cultures of specific pathogens. The multi-microbial real-time PCR system revealed profiles of microorganism infection in lung samples collected at autopsy from 10 patients with acquired immunodeficiency syndrome. Staphylococcus aureus was the most common microbe detected (n=8), but with low copy numbers. High copy numbers of Pseudomonas aeruginosa were detected in the lung samples with abscess (n=6). Enterococcus faecium (n=6), Elizabethkingia meningoseptica (n=4), and Candida albicans (n=4) were also frequently detected. In addition, a latent infection of Mycobacterium tuberculosis was detected in one case of pneumonia. In conclusion, this multi-microbial real-time PCR system can be useful for detecting bacteria and fungi in pathological specimens from patients with uncertain diagnoses. PMID- 26823920 TI - Expression and function of microRNA-188-5p in activated rheumatoid arthritis synovial fibroblasts [Retraction]. PMID- 26823919 TI - Knockdown of WISP1 inhibit proliferation and induce apoptosis in ALL Jurkat cells. AB - WISP1, a Wnt-induced secreted protein, has been found to have anticancer activity. ALL is a leading cause of death. Here we investigate the WISP1 effects on ALL Jurkat cells. Cell viability was assessed by CCK-8. Cell cycle and apoptosis were detected by flow cytometry. Mitochondrial membrane potential (MMP) was monitored using TMRM. Generation of reactive oxygen species (ROS) was quantified using DCFH-DA. Western blot was used to detect the expression of cell proliferation and apoptosis related genes. The results showed that knockdown of WISP1 significantly inhibited proliferation of Jurkat cells. Parallelly, cell cycle distribution was increased at G1 phase and apoptotic rate was induced after WISP1 knockdown. Furthermore, knockdown of WISP1 induced apoptosis of Jurkat cells was also associated with loss of MMP and generation of ROS. Western blot results showed that the protein expression p-AKT, PCNA, CDK1, P-ERK, CDK2, VEGF, VEGFR2 and Bcl2 were decreased, while the expression of Bax was up-regulated. In conclusion, WISP1 plays an important role in proliferation and apoptosis of Jurkat cells in mitochondria dependent pathway, the specific mechanisms need further study. PMID- 26823921 TI - An introduction to this Special Issue: Chemosensation and Health. PMID- 26823922 TI - The San Bernardino, California, Terror Attack: Two Emergency Departments' Response. AB - On December 2, 2015, a terror attack in the city of San Bernardino, California killed 14 Americans and injured 22 in the deadliest attack on U.S. soil since September 11, 2001. Although emergency personnel and law enforcement officials frequently deal with multi-casualty incidents (MCIs), what occurred that day required an unprecedented response. Most of the severely injured victims were transported to either Loma Linda University Medical Center (LLUMC) or Arrowhead Regional Medical Center (ARMC). These two hospitals operate two designated trauma centers in the region and played crucial roles during the massive response that followed this attack. In an effort to shed a light on our response to others, we provide an account of how these two teaching hospitals prepared for and coordinated the medical care of these victims. In general, both centers were able to quickly mobilize large number of staff and resources. Prior disaster drills proved to be invaluable. Both centers witnessed excellent teamwork and coordination involving first responders, law enforcement, administration, and medical personnel from multiple specialty services. Those of us working that day felt safe and protected. Although we did identify areas we could have improved upon, including patchy communication and crowd-control, they were minor in nature and did not affect patient care. MCIs pose major challenges to emergency departments and trauma centers across the country. Responding to such incidents requires an ever-evolving approach as no two incidents will present exactly alike. It is our hope that this article will foster discussion and lead to improvements in management of future MCIs. PMID- 26823923 TI - Lethal Means Counseling for Parents of Youth Seeking Emergency Care for Suicidality. AB - INTRODUCTION: A youth's emergency department (ED) visit for suicidal behaviors or ideation provides an opportunity to counsel families about securing medications and firearms (i.e., lethal means counseling). METHODS: In this quality improvement project drawing on the Counseling on Access to Lethal Means (CALM) model, we trained 16 psychiatric emergency clinicians to provide lethal means counseling with parents of patients under age 18 receiving care for suicidality and discharged home from a large children's hospital. Through chart reviews and follow-up interviews of parents who received the counseling, we examined what parents recalled, their reactions to the counseling session, and actions taken after discharge. RESULTS: Between March and July 2014, staff counseled 209 of the 236 (89%) parents of eligible patients. We conducted follow-up interviews with 114 parents, or 55% of those receiving the intervention; 48% of those eligible. Parents had favorable impressions of the counseling and good recall of the main messages. Among the parents contacted at follow up, 76% reported all medications in the home were locked as compared to fewer than 10% at the time of the visit. All who had indicated there were guns in the home at the time of the visit reported at follow up that all were currently locked, compared to 67% reporting this at the time of the visit. CONCLUSION: Though a small project in just one hospital, our findings demonstrate the feasibility of adding a counseling protocol to the discharge process within a pediatric psychiatric emergency service. Our positive findings suggest that further study, including a randomized control trial in more facilities, is warranted. PMID- 26823924 TI - Emergency Physicians as Good Samaritans: Survey of Frequency, Locations, Supplies and Medications. AB - INTRODUCTION: Little is known about the frequency and locations in which emergency physicians (EPs) are bystanders to an accident or emergency; equally uncertain is which contents of an "emergency kit" may be useful during such events. The aim of this study was to describe the frequency and locations of Good Samaritan acts by EPs and also determine which emergency kit supplies and medications were most commonly used by Good Samaritans. METHODS: We conducted an electronic survey among a convenience sample of EPs in Colorado. RESULTS: Respondents reported a median frequency of 2.0 Good Samaritan acts per five years of practice, with the most common locations being sports and entertainment events (25%), road traffic accidents (21%), and wilderness settings (19%). Of those who had acted as Good Samaritans, 86% reported that at least one supply would have been useful during the most recent event, and 66% reported at least one medication would have been useful. The most useful supplies were gloves (54%), dressings (34%), and a stethoscope (20%), while the most useful medications were oxygen (19%), intravenous fluids (17%), and epinephrine (14%). CONCLUSION: The majority of EPs can expect to provide Good Samaritan care during their careers and would be better prepared by carrying a kit with common supplies and medications where they are most likely to use them. PMID- 26823925 TI - Access to In-Network Emergency Physicians and Emergency Departments Within Federally Qualified Health Plans in 2015. AB - INTRODUCTION: Under regulations established by the Affordable Care Act, insurance plans must meet minimum standards in order to be sold through the federal Marketplace. These standards to become a qualified health plan (QHP) include maintaining a provider network sufficient to assure access to services. However, the complexity of emergency physician (EP) employment practices - in which the EPs frequently serve as independent contractors of emergency departments, independently establish insurance contracts, etc... - and regulations governing insurance repayment may hinder the application of network adequacy standards to emergency medicine. As such, we hypothesized the existence of QHPs without in network access to EPs. The objective is to identify whether there are QHPs without in-network access to EPs using information available through the federal Marketplace and publicly available provider directories. RESULTS: In a national sample of Marketplace plans, we found that one in five provider networks lacks identifiable in-network EPs. QHPs lacking EPs spanned nearly half (44%) of the 34 states using the federal Marketplace. CONCLUSION: Our data suggest that the present regulatory framework governing network adequacy is not generalizable to emergency care, representing a missed opportunity to protect patient access to in network physicians. These findings and the current regulations governing insurance payment to EPs dis-incentivize the creation of adequate physician networks, incentivize the practice of balance billing, and shift the cost burden to patients. PMID- 26823926 TI - Association of Insurance Status with Severity and Management in ED Patients with Asthma Exacerbation. AB - INTRODUCTION: Previous studies have demonstrated an association of low socioeconomic status with frequent asthma exacerbations. However, there have been no recent multicenter efforts to examine the relationship of insurance status - a proxy for socioeconomic status - with asthma severity and management in adults. The objective is to investigate chronic and acute asthma management disparities by insurance status among adults requiring emergency department (ED) treatment in the United States. METHODS: We conducted a multicenter chart review study (48 EDs in 23 U.S. states) on ED patients, aged 18-54 years, with acute asthma between 2011 and 2012. Each site underwent training (lecture, practice charts, certification) before reviewing randomly selected charts. We categorized patients into three groups based on their primary health insurance: private, public, and no insurance. Outcome measures were chronic asthma severity (as measured by >=2 ED visits in one-year period) and management prior to the index ED visit, acute asthma management in the ED, and prescription at ED discharge. RESULTS: The analytic cohort comprised 1,928 ED patients with acute asthma. Among these, 33% had private insurance, 40% had public insurance, and 27% had no insurance. Compared to patients with private insurance, those with public insurance or no insurance were more likely to have >=2 ED visits during the preceding year (35%, 49%, and 45%, respectively; p<0.001). Despite the higher chronic severity, those with no insurance were less likely to have guideline-recommended chronic asthma care - i.e., lower use of inhaled corticosteroids (ICS [41%, 41%, and 29%; p<0.001]) and asthma specialist care (9%, 10%, and 4%; p<0.001). By contrast, there were no significant differences in acute asthma management in the ED - e.g., use of systemic corticosteroids (75%, 79%, and 78%; p=0.08) or initiation of ICS at ED discharge (12%, 12%, and 14%; p=0.57) - by insurance status. CONCLUSION: In this multicenter observational study of ED patients with acute asthma, we found significant discrepancies in chronic asthma severity and management by insurance status. By contrast, there were no differences in acute asthma management among the insurance groups. PMID- 26823927 TI - Randomized Controlled Trial of Electronic Care Plan Alerts and Resource Utilization by High Frequency Emergency Department Users with Opioid Use Disorder. AB - INTRODUCTION: There is a paucity of literature supporting the use of electronic alerts for patients with high frequency emergency department (ED) use. We sought to measure changes in opioid prescribing and administration practices, total charges and other resource utilization using electronic alerts to notify providers of an opioid-use care plan for high frequency ED patients. METHODS: This was a randomized, non-blinded, two-group parallel design study of patients who had 1) opioid use disorder and 2) high frequency ED use. Three affiliated hospitals with identical electronic health records participated. Patients were randomized into "Care Plan" versus "Usual Care groups". Between the years before and after randomization, we compared as primary outcomes the following: 1) opioids (morphine mg equivalents) prescribed to patients upon discharge and administered to ED and inpatients; 2) total medical charges, and the numbers of; 3) ED visits, 4) ED visits with advanced radiologic imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) studies, and 5) inpatient admissions. RESULTS: A total of 40 patients were enrolled. For ED and inpatients in the "Usual Care" group, the proportion of morphine mg equivalents received in the post-period compared with the pre-period was 15.7%, while in the "Care Plan" group the proportion received in the post-period compared with the pre-period was 4.5% (ratio=0.29, 95% CI [0.07-1.12]; p=0.07). For discharged patients in the "Usual Care" group, the proportion of morphine mg equivalents prescribed in the post-period compared with the pre-period was 25.7% while in the "Care Plan" group, the proportion prescribed in the post-period compared to the pre-period was 2.9%. The "Care Plan" group showed an 89% greater proportional change over the periods compared with the "Usual Care" group (ratio=0.11, 95% CI [0.01 0.092]; p=0.04). Care plans did not change the total charges, or, the numbers of ED visits, ED visits with CT or MRI or inpatient admissions. CONCLUSION: Electronic care plans were associated with an incremental decrease in opioids (in morphine mg equivalents) prescribed to patients with opioid use disorder and high frequency ED use. PMID- 26823928 TI - Frequency of Fractures Identified on Post-Reduction Radiographs After Shoulder Dislocation. AB - INTRODUCTION: Most emergency physicians routinely obtain shoulder radiographs before and after shoulder dislocations. However, currently there is limited literature demonstrating how frequently new fractures are identified on post reduction radiographs. The primary objective of this study was to determine the frequency of new, clinically significant fractures identified on post-reduction radiographs with a secondary outcome assessing total new fractures identified. METHODS: We conducted a retrospective chart review using appropriate International Classification of Diseases, 9(th) Revision (ICD-9) codes to identify all potential shoulder dislocations that were reduced in a single, urban, academic emergency department (ED) over a five-year period. We excluded cases that required operative reduction, had associated proximal humeral head or shaft fractures, or were missing one or more shoulder radiograph reports. All charts were abstracted separately by two study investigators with disagreements settled by consensus among three investigators. Images from indeterminate cases were reviewed by a radiology attending physician with musculoskeletal expertise. The primary outcome was the percentage of new, clinically significant fractures defined as those altering acute ED management. Secondary outcomes included percentage of new fractures of any type. RESULTS: We identified 185 total patients meeting our study criteria. There were no new, clinically significant fractures on post-reduction radiographs. There were 13 (7.0%; 95% CI [3.3% 10.7%]) total new fractures identified, all of which were without clinical significance for acute ED management. CONCLUSION: Post-reduction radiographs do not appear to identify any new, clinically significant fractures. Practitioners should re-consider the use of routine post-reduction radiographs in the ED setting for shoulder dislocations. PMID- 26823929 TI - Identifying Frequent Users of an Urban Emergency Medical Service Using Descriptive Statistics and Regression Analyses. AB - This retrospective cohort study provides a descriptive analysis of a population that frequently uses an urban emergency medical service (EMS) and identifies factors that contribute to use among all frequent users. For purposes of this study we divided frequent users into the following groups: low- frequent users (4 EMS transports in 2012), medium-frequent users (5 to 6 EMS transports in 2012), high-frequent users (7 to 10 EMS transports in 2012) and super-frequent users (11 or more EMS transports in 2012). Overall, we identified 539 individuals as frequent users. For all groups of EMS frequent users (i.e. low, medium, high and super) one or more hospital admissions, receiving a referral for follow-up care upon discharge, and having no insurance were found to be statistically significant with frequent EMS use (P<0.05). Within the diagnostic categories, 41.61% of super-frequent users had a diagnosis of "primarily substance abuse/misuse" and among low-frequent users a majority, 53.33%, were identified as having a "reoccurring (medical) diagnosis." Lastly, relative risk ratios for the highest group of users, super-frequent users, were 3.34 (95% CI [1.90-5.87]) for obtaining at least one referral for follow-up care, 13.67 (95% CI [5.60-33.34]) for having four or more hospital admissions and 5.95 (95% CI [1.80-19.63]) for having a diagnoses of primarily substance abuse/misuse. Findings from this study demonstrate that among low- and medium-frequent users a majority of patients are using EMS for reoccurring medical conditions. This could potentially be avoided with better care management. In addition, this study adds to the current literature that illustrates a strong correlation between substance abuse/misuse and high/super-frequent EMS use. For the subgroup analysis among individuals 65 years of age and older, we did not find any of the independent variables included in our model to be statistically significant with frequent EMS use. PMID- 26823930 TI - Point-of-Care Multi-Organ Ultrasound Improves Diagnostic Accuracy in Adults Presenting to the Emergency Department with Acute Dyspnea. AB - INTRODUCTION: Determining the etiology of acute dyspnea in emregency department (ED) patients is often difficult. Point-of-care ultrasound (POCUS) holds promise for improving immediate diagnostic accuracy (after history and physical), thus improving use of focused therapies. We evaluate the impact of a three-part POCUS exam, or "triple scan" (TS) - composed of abbreviated echocardiography, lung ultrasound and inferior vena cava (IVC) collapsibility assessment - on the treating physician's immediate diagnostic impression. METHODS: A convenience sample of adults presenting to our urban academic ED with acute dyspnea (Emergency Severity Index 1, 2) were prospectively enrolled when investigator sonographers were available. The method for performing components of the TS has been previously described in detail. Treating physicians rated the most likely diagnosis after history and physical but before other studies (except electrocardiogram) returned. An investigator then performed TS and disclosed the results, after which most likely diagnosis was reassessed. Final diagnosis (criterion standard) was based on medical record review by expert emergency medicine faculty blinded to TS result. We compared accuracy of pre-TS and post-TS impression (primary outcome) with McNemar's test. Test characteristics for treating physician impression were also calculated by dichotomizing acute decompensated heart failure (ADHF), chronic obstructive pulmonary disease (COPD) and pneumonia as present or absent. RESULTS: 57 patients were enrolled with the leading final diagnoses being ADHF (26%), COPD/asthma (30%), and pneumonia (28%). Overall accuracy of the treating physician's impression increased from 53% before TS to 77% after TS (p=0.003). The post-TS impression was 100% sensitive and 84% specific for ADHF. CONCLUSION: In this small study, POCUS evaluation of the heart, lungs and IVC improved the treating physician's immediate overall diagnostic accuracy for ADHF, COPD/asthma and pneumonia and was particularly useful to immediately exclude ADHF as the cause of acute dyspnea. PMID- 26823931 TI - Strain Echocardiography in Acute Cardiovascular Diseases. AB - Echocardiography has become a critical tool in the evaluation of patients presenting to the emergency department (ED) with acute cardiovascular diseases and undifferentiated cardiopulmonary symptoms. New technological advances allow clinicians to accurately measure left ventricular (LV) strain, a superior marker of LV systolic function compared to traditional measures such as ejection fraction, but most emergency physicians (EPs) are unfamiliar with this method of echocardiographic assessment. This article discusses the application of LV longitudinal strain in the ED and reviews how it has been used in various disease states including acute heart failure, acute coronary syndromes (ACS) and pulmonary embolism. It is important for EPs to understand the utility of technological and software advances in ultrasound and how new methods can build on traditional two-dimensional and Doppler techniques of standard echocardiography. The next step in competency development for EP-performed focused echocardiography is to adopt novel approaches such as strain using speckle-tracking software in the management of patients with acute cardiovascular disease. With the advent of speckle tracking, strain image acquisition and interpretation has become semi-automated making it something that could be routinely added to the sonographic evaluation of patients presenting to the ED with cardiovascular disease. Once strain imaging is adopted by skilled EPs, focused echocardiography can be expanded and more direct, phenotype-driven care may be achievable for ED patients with a variety of conditions including heart failure, ACS and shock. PMID- 26823932 TI - Ultrasound Evaluation of Upper Extremity Deformity. PMID- 26823933 TI - Emergency Medicine Resident Rotations Abroad: Current Status and Next Steps. AB - INTRODUCTION: International rotations for residents are increasingly popular, but there is a dearth of evidence to demonstrate that these rotations are safe and that residents have appropriate training and support to conduct them. METHODS: A survey was sent to all U.S. emergency medicine (EM) residencies with publicly available e-mail addresses. The survey documents and examines the training and support that emergency medicine residents are offered for international rotations and the frequency of adverse safety events. RESULTS: 72.5% of program director responded that their residents are participating in rotations abroad. However, only 15.4% of programs reported offering training specific to working abroad. The results point to an increased need for specific training and insurance coverage. CONCLUSION: Oversight of international rotations should be improved to guarantee safety and education benefit. PMID- 26823934 TI - Emergency Department of a Rural Hospital in Ecuador. AB - INTRODUCTION: There is a paucity of data studying patients and complaints presenting to emergency departments (EDs) in low- and middle-income countries. The town of Pedro Vicente Maldonado (PVM) is located in the northwestern highlands of Ecuador. Hospital PVM (HPVM) is a rural teaching hospital providing family medicine residency training. These physicians provide around-the-clock acute medical care in HPVM's ED. This study provides a first look at a functioning ED in rural Latin America by reviewing one year of ED visits to HPVM. METHODS: All ED visits between April 14, 2013, and April 13, 2014, were included and analyzed, totaling 1,239 patient visits. Data were collected from their electronic medical record and exported into a de-identified Excel(r) database where it was sorted and categorized. Variables included age, gender, mode of arrival, insurance type, month and day of the week of the service, chief complaint, laboratory and imaging requests, and disposition. We performed descriptive statistics, and where possible, comparisons using Student's T or chi square, as appropriate. RESULTS: Of the 1239 total ED visits, 48% were males and 52% females; 93% of the visits were ambulatory, and 7% came by ambulance. Sixty three percent of the patients had social security insurance. The top three chief complaints were abdominal pain (25.5%), fever (15.1%) and trauma (10.8%). Healthcare providers requested labs on 71.3% of patients and imaging on 43.2%. The most frequently requested imaging studies were chest radiograph (14.9%), upper extremity radiograph (9.4%), and electrocardiogram (9.0%). There was no seasonal or day-of-week variability to number of ED patients. The chief complaint of human or animal bite made it more likely the patient would be admitted, and the chief complaint of traumatic injury made it more likely the patient would be transferred. CONCLUSION: Analysis of patients presenting to a rural ED in Ecuador contributes to the global study of acute care in the developing world and also provides a self-analysis identifying disease patterns of the area, training topics for residents, areas for introducing protocols, and information to help planning for rural EDs in low- and middle-income countries. PMID- 26823935 TI - Crossing Borders. PMID- 26823936 TI - Medication Overdoses at a Public Emergency Department in Santiago, Chile. AB - INTRODUCTION: While a nationwide poison control registry exists in Chile, reporting to the center is sporadic and happens at the discretion of the treating physician or by patients' self-report. Moreover, individual hospitals do not monitor accidental or intentional poisoning in a systematic manner. The goal of this study was to identify all cases of intentional medication overdose (MO) that occurred over two years at a large public hospital in Santiago, Chile, and examine its epidemiologic profile. METHODS: This study is a retrospective, explicit chart review conducted at Hospital Sotero del Rio from July 2008 until June 2010. We included all cases of identified intentional MO. Alcohol and recreational drugs were included only when they were ingested with other medications. RESULTS: We identified 1,557 cases of intentional MO and analyzed a total of 1,197 cases, corresponding to 0.51% of all emergency department (ED) presentations between July 2008 and June 2010. The median patient age was 25 years. The majority was female (67.6%). Two peaks were identified, corresponding to the spring of each year sampled. The rate of hospital admission was 22.2%. Benzodiazepines, selective serotonin reuptake inhibitors, and tricyclic antidepressants (TCA) were the causative agents most commonly found, comprising 1,044 (87.2%) of all analyzed cases. Acetaminophen was involved in 81 (6.8%) cases. More than one active substance was involved in 35% of cases. In 7.3% there was ethanol co-ingestion and in 1.0% co-ingestion of some other recreational drug (primarily cocaine). Of 1,557 cases, six (0.39%) patients died. TCA were involved in two of these deaths. CONCLUSION: Similar to other developed and developing nations, intentional MO accounts for a significant number of ED presentations in Chile. Chile is unique in the region, however, in that its spectrum of intentional overdoses includes an excess burden of tricyclic antidepressant and benzodiazepine overdoses, a relatively low rate of alcohol and recreational drug co-ingestion, and a relatively low rate of acetaminophen ingestion. PMID- 26823937 TI - Seldinger Technique for Placement of "Peripheral" Internal Jugular Line: Novel Approach for Emergent Vascular Access. AB - This is a case report describing the ultrasound-guided placement of a peripheral intravenous catheter into the internal jugular vein of a patient with difficult vascular access. Although this technique has been described in the past, this case is novel in that the Seldinger technique was used to place the catheter. This allows for safer placement of a longer catheter (2.25") without the need for venous dilation, which is potentially hazardous. PMID- 26823938 TI - Shot in the Heart. PMID- 26823939 TI - A Rare Cause of Headache. PMID- 26823940 TI - Tension Hydrothorax from Disseminated Endometriosis. PMID- 26823941 TI - Frozen Funding on Firearm Research: "Doing Nothing Is No Longer an Acceptable Solution". PMID- 26823942 TI - In Response to: Poisonings with Suicidal Intent Aged 0-21 Years Reported to Poison Centers 2003-12. PMID- 26823943 TI - Response to Comments on "Poisonings with Suicidal Intent Aged 0-21 Years Reported to Poison Centers 2003-12". PMID- 26823944 TI - Possible Biomarkers in Blood for Crohn's Disease: Oxidative Stress and MicroRNAs Current Evidences and Further Aspects to Unravel. AB - Crohn's disease (CD) is an inflammatory disorder characterised by a transmural inflammation of the intestinal wall. Although the physiopathology of the disease is not yet fully understood, it is clear that the immune response plays an important role in it. This hyperreactive immune system is accompanied by the presence of unregulated reactive oxygen species (ROS). These elements are modulated in normal conditions by different elements, including enzymes that function as antioxidant defences preventing the harmful effects of ROS. However, in CD there is an imbalance between ROS production and these antioxidant elements, resulting in oxidative stress (OxS) phenomena. In fact, now OxS is being considered more a potential etiological factor for Crohn's disease rather than a concomitant effect in the disease. The persistence of the OxS can also be influencing the evolution of the disease. Furthermore, the epigenetic mechanisms, above all microRNAs, are being considered key elements in the pathogenesis of CD. These elements and the presence of OxS have also been linked to several diseases. We, therefore, describe in this review the most significant findings related to oxidative stress and microRNAs profiles in the peripheral blood of CD patients. PMID- 26823945 TI - BQ123 Stimulates Skeletal Muscle Antioxidant Defense via Nrf2 Activation in LPS Treated Rats. AB - Little is understood of skeletal muscle tissue in terms of oxidative stress and inflammation. Endothelin-1 is an endogenous, vasoconstrictive peptide which can induce overproduction of reactive oxygen species and proinflammatory cytokines. The aim of this study was to evaluate whether BQ123, an endothelin-A receptor antagonist, influences the level of TNF-alpha, IL-6, SOD-1, HO-1, Nrf2 mRNA, and NF-kappaB subunit RelA/p65 mRNA in the femoral muscle obtained from endotoxemic rats. Male Wistar rats were divided into 4 groups (n = 6) and received iv (1) saline (control), (2) LPS (15 mg/kg), (3) BQ123 (1 mg/kg), (4) BQ123 (1 mg/kg), and LPS (15 mg/kg, resp.) 30 min later. Injection of LPS led to significant increase in levels of RelA/p65 mRNA, TNF-alpha, and IL-6, while content of SOD-1, HO-1, and Nrf2 mRNA was unchanged. Administration of BQ123 prior to LPS challenge resulted in a significant reduction in RelA/p65 mRNA, TNF-alpha, and IL-6 levels, as well as markedly elevated concentrations of SOD-1, HO-1, and Nrf2 mRNA. BQ123 appears to enhance antioxidant defense and prevent production of TNF-alpha and IL 6 in skeletal muscle of LPS-treated rat. In conclusion, endothelin-A receptor antagonism exerts significant impact on the skeletal muscle favouring anti inflammatory effects and protection against oxidative stress. PMID- 26823946 TI - Modulation of Hydrogen Peroxide-Induced Oxidative Stress in Human Neuronal Cells by Thymoquinone-Rich Fraction and Thymoquinone via Transcriptomic Regulation of Antioxidant and Apoptotic Signaling Genes. AB - Nigella sativa Linn. (N. sativa) and its bioactive constituent Thymoquinone (TQ) have demonstrated numerous pharmacological attributes. In the present study, the neuroprotective properties of Thymoquinone-rich fraction (TQRF) and TQ against hydrogen peroxide- (H2O2-) induced neurotoxicity in differentiated human SH-SY5Y cells were investigated. TQRF was extracted using supercritical fluid extraction while TQ was acquired commercially, and their effects on H2O2 were evaluated using cell viability assay, reactive oxygen species (ROS) assay, morphological observation, and multiplex gene expression. Both TQRF and TQ protected the cells against H2O2 by preserving the mitochondrial metabolic enzymes, reducing intracellular ROS levels, preserving morphological architecture, and modulating the expression of genes related to antioxidants (SOD1, SOD2, and catalase) and signaling genes (p53, AKT1, ERK1/2, p38 MAPK, JNK, and NF-kappabeta). In conclusion, the enhanced efficacy of TQRF over TQ was likely due to the synergism of multiple constituents in TQRF. The efficacy of TQRF was better than that of TQ alone when equal concentrations of TQ in TQRF were compared. In addition, TQRF also showed comparable effects to TQ when the same concentrations were tested. These findings provide further support for the use of TQRF as an alternative to combat oxidative stress insults in neurodegenerative diseases. PMID- 26823947 TI - From Six Gene Polymorphisms of the Antioxidant System, Only GPX Pro198Leu and GSTP1 Ile105Val Modulate the Risk of Acute Myeloid Leukemia. AB - Oxidative stress might contribute to the occurrence of cancers, including the hematological ones. Various genetic polymorphisms were shown to increase the quantity of reactive oxygen species, a phenomenon that is able to induce mutations and thus promote cancers. The purpose of the study was to evaluate the association between CAT C262T, GPX1 Pro198Leu, MnSOD Ala16Val, GSTM1, GSTT1, and GSTP1 Ile105Val gene polymorphisms and acute myeloid leukemia risk, in a case control study comprising 102 patients and 303 controls. No association was observed between AML and variant genotypes of CAT, MnSOD, GSTM1, and GSTT1 polymorphisms. Our data revealed a statistically significant difference regarding the frequencies of GPX1 Pro198Leu and GSTP1 Ile105Val variant genotypes between AML patients and controls (p < 0.001). Our results showed no association in the distribution of any of the CAT C262T, GPX1 Pro198Leu, GSTM1, GSTT1, and GSTP1 polymorphisms regarding age, gender, FAB subtype, cytogenetic risk groups, FLT3 and DNMT3 gene mutations, and overall survival. Our data suggests that the presence of variant allele and genotype of GPX1 Pro198Leu and GSTP1 Ile105Val gene polymorphisms may modulate the risk of developing AML. PMID- 26823948 TI - Inhibition of the RhoA GTPase Activity Increases Sensitivity of Melanoma Cells to UV Radiation Effects. AB - Ultraviolet radiation is the main cause of DNA damage to melanocytes and development of melanoma, one of the most lethal human cancers, which leads to metastasis due to uncontrolled cell proliferation and migration. These phenotypes are mediated by RhoA, a GTPase overexpressed or overactivated in highly aggressive metastatic tumors that plays regulatory roles in cell cycle progression and cytoskeleton remodeling. This work explores whether the effects of UV on DNA damage, motility, proliferation, and survival of human metastatic melanoma cells are mediated by the RhoA pathway. Mutant cells expressing dominant negative (MeWo-RhoA-N19) or constitutively active RhoA (MeWo-RhoA-V14) were generated and subjected to UV radiation. A slight reduction in migration and invasion was observed in MeWo and MeWo-RhoA-V14 cells but not in MeWo-RhoA-N19 cells, which presented inefficient motility and invasiveness associated with stress fibers fragmentation. Proliferation and survival of RhoA-deficient cells were drastically reduced by UV compared to cells displaying normal or high RhoA activity, suggesting increased sensitivity to UV. Loss of RhoA activity also caused less efficient DNA repair, with elevated levels of DNA lesions such as strand breaks and cyclobutane pyrimidine dimers (CPDs). Thus, RhoA mediates genomic stability and represents a potential target for sensitizing metastatic tumors to genotoxic agents. PMID- 26823949 TI - Hydrogen Sulfide Inhibits High-Salt Diet-Induced Renal Oxidative Stress and Kidney Injury in Dahl Rats. AB - BACKGROUND. The study was designed to investigate if H2S could inhibit high-salt diet-induced renal excessive oxidative stress and kidney injury in Dahl rats. METHODS. Male salt-sensitive Dahl and SD rats were used. Blood pressure (BP), serum creatinine, urea, creatinine clearance rate, and 24-hour urine protein were measured. Renal ultra- and microstructures were observed. Collagen-I and -III contents the oxidants and antioxidants levels in renal tissue were detected. Keap1/Nrf2 association and Keap1 s-sulfhydration were detected. RESULTS. After 8 weeks of high-salt diet, BP was significantly increased, renal function and structure were impaired, and collagen deposition was abundant in renal tissues with increased renal MPO activity, H2O2, MDA, GSSG, and (*)OH contents, reduced renal T-AOC and GSH contents, CAT, GSH-PX and SOD activity, and SOD expressions in Dahl rats. Furthermore, endogenous H2S in renal tissues was decreased in Dahl rats. H2S donor, however, decreased BP, improved renal function and structure, and inhibited collagen excessive deposition in kidney, in association with increased antioxidative activity and reduced oxidative stress in renal tissues. H2S activated Nrf2 by inducing Keap1 s-sulfhydration and subsequent Keap1/Nrf2 disassociation. CONCLUSIONS. H2S protected against high-salt diet-induced renal injury associated with enhanced antioxidant capacity and inhibited renal oxidative stress. PMID- 26823950 TI - Xanthine Oxidoreductase-Derived Reactive Species: Physiological and Pathological Effects. AB - Xanthine oxidoreductase (XOR) is the enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid and is widely distributed among species. In addition to this housekeeping function, mammalian XOR is a physiological source of superoxide ion, hydrogen peroxide, and nitric oxide, which can function as second messengers in the activation of various pathways. This review intends to address the physiological and pathological roles of XOR derived oxidant molecules. The cytocidal action of XOR products has been claimed in relation to tissue damage, in particular damage induced by hypoxia and ischemia. Attempts to exploit this activity to eliminate unwanted cells via the construction of conjugates have also been reported. Moreover, different aspects of XOR activity related to phlogosis, endothelial activation, leukocyte activation, and vascular tone regulation, have been taken into consideration. Finally, the positive and negative outcomes concerning cancer pathology have been analyzed because XOR products may induce mutagenesis, cell proliferation, and tumor progression, but they are also associated with apoptosis and cell differentiation. In conclusion, XOR activity generates free radicals and other oxidant reactive species that may result in either harmful or beneficial outcomes. PMID- 26823951 TI - SOD1 Overexpression Preserves Baroreflex Control of Heart Rate with an Increase of Aortic Depressor Nerve Function. AB - Overproduction of reactive oxygen species (ROS), such as the superoxide radical (O2 (?-)), is associated with diseases which compromise cardiac autonomic function. Overexpression of SOD1 may offer protection against ROS damage to the cardiac autonomic nervous system, but reductions of O2 (?-) may interfere with normal cellular functions. We have selected the C57B6SJL-Tg (SOD1)2 Gur/J mouse as a model to determine whether SOD1 overexpression alters cardiac autonomic function, as measured by baroreflex sensitivity (BRS) and aortic depressor nerve (ADN) recordings, as well as evaluation of baseline heart rate (HR) and mean arterial pressure (MAP). Under isoflurane anesthesia, C57 wild-type and SOD1 mice were catheterized with an arterial pressure transducer and measurements of HR and MAP were taken. After establishing a baseline, hypotension and hypertension were induced by injection of sodium nitroprusside (SNP) and phenylephrine (PE), respectively, and DeltaHR versus DeltaMAP were recorded as a measure of baroreflex sensitivity (BRS). SNP and PE treatment were administered sequentially after a recovery period to measure arterial baroreceptor activation by recording aortic depressor nerve activity. Our findings show that overexpression of SOD1 in C57B6SJL-Tg (SOD1)2 Gur/J mouse preserved the normal HR, MAP, and BRS but enhanced aortic depressor nerve function. PMID- 26823953 TI - Hericium erinaceus Inhibits TNF-alpha-Induced Angiogenesis and ROS Generation through Suppression of MMP-9/NF-kappaB Signaling and Activation of Nrf2-Mediated Antioxidant Genes in Human EA.hy926 Endothelial Cells. AB - Hericium erinaceus (HE) is an edible mushroom that has been shown to exhibit anticancer and anti-inflammatory activities. We investigated the antiangiogenic and antioxidant potentials of ethanol extracts of HE in human endothelial (EA.hy926) cells upon tumor necrosis factor-alpha- (TNF-alpha-) stimulation (10 ng/mL). The underlying molecular mechanisms behind the pharmacological efficacies were elucidated. We found that noncytotoxic concentrations of HE (50-200 MUg/mL) significantly inhibited TNF-alpha-induced migration/invasion and capillary-like tube formation of endothelial cells. HE treatment suppressed TNF-alpha-induced activity and/or overexpression of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). Furthermore, HE downregulated TNF alpha-induced nuclear translocation and transcriptional activation of nuclear factor-kappaB (NF-kappaB) followed by suppression of I-kappaB (inhibitor-kappaB) degradation. Data from fluorescence microscopy illustrated that increased intracellular ROS production upon TNF-alpha-stimulation was remarkably inhibited by HE pretreatment in a dose-dependent manner. Notably, HE triggered antioxidant gene expressions of heme oxygenase-1 (HO-1), gamma-glutamylcysteine synthetase (gamma-GCLC), and glutathione levels, which may contribute to inhibition of ROS. Increased antioxidant status was associated with upregulated nuclear translocation and transcriptional activation of NF-E2 related factor-2 (Nrf2) in HE treated cells. Our findings conclude that antiangiogenic and anti-inflammatory activities of H. erinaceus may contribute to its anticancer property through modulation of MMP-9/NF-kappaB and Nrf2-antioxidant signaling pathways. PMID- 26823955 TI - Reinforced Epithelial Barrier Integrity via Matriptase Induction with Sphingosine 1-Phosphate Did Not Result in Disturbances in Physiological Redox Status. AB - Objectives. The relationship among matriptase function, cellular redox status, and maintenance of intestinal barrier integrity has not been established yet. The aim of this study is to reveal if the crosstalk between matriptase activators and intestinal epithelial monolayers can lead to perturbations in physiological redox regulation in vitro. Methods. The effects of suramin and sphingosine-1-phosphate (S1P) were tested on viability of intestinal porcine epithelial IPEC-J2 cells using MTS assay. Measurements of transepithelial electrical resistance (TER) were performed to determine changes in barrier integrity of cell monolayers. Amplex Red assay was used to monitor extracellular hydrogen peroxide production. Occludin distribution pattern was detected prior to and after matriptase activation using immunofluorescent staining technique. Results. TER reduction was observed in suramin-treated IPEC-J2 cell monolayers, which could be attributed to cell cytotoxic properties of 48 hr 50 MUM suramin administration. In contrast, S1P treatment increased TER significantly and elevated occludin accumulation in tight junctions. It was also found that extracellular hydrogen peroxide levels were maintained in IPEC-J2 cells exposed to matriptase activators. Discussion. S1P administration not accompanied by redox imbalance might be one of the key strategies in the improvement of barrier function and consequently in the therapy of intestinal inflammations. PMID- 26823954 TI - Cardiovascular and Hepatic Toxicity of Cocaine: Potential Beneficial Effects of Modulators of Oxidative Stress. AB - Oxidative stress (OS) is thought to play an important role in the pharmacological and toxic effects of various drugs of abuse. Herein we review the literature on the mechanisms responsible for the cardiovascular and hepatic toxicity of cocaine with special focus on OS-related mechanisms. We also review the preclinical and clinical literature concerning the putative therapeutic effects of OS modulators (such as N-acetylcysteine, superoxide dismutase mimetics, nitroxides and nitrones, NADPH oxidase inhibitors, xanthine oxidase inhibitors, and mitochondriotropic antioxidants) for the treatment of cocaine toxicity. We conclude that available OS modulators do not appear to have clinical efficacy. PMID- 26823952 TI - Exercise Modulates Oxidative Stress and Inflammation in Aging and Cardiovascular Diseases. AB - Despite the wealth of epidemiological and experimental studies indicating the protective role of regular physical activity/exercise training against the sequels of aging and cardiovascular diseases, the molecular transducers of exercise/physical activity benefits are not fully identified but should be further investigated in more integrative and innovative approaches, as they bear the potential for transformative discoveries of novel therapeutic targets. As aging and cardiovascular diseases are associated with a chronic state of oxidative stress and inflammation mediated via complex and interconnected pathways, we will focus in this review on the antioxidant and anti-inflammatory actions of exercise, mainly exerted on adipose tissue, skeletal muscles, immune system, and cardiovascular system by modulating anti-inflammatory/proinflammatory cytokines profile, redox-sensitive transcription factors such as nuclear factor kappa B, activator protein-1, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, antioxidant and prooxidant enzymes, and repair proteins such as heat shock proteins, proteasome complex, oxoguanine DNA glycosylase, uracil DNA glycosylase, and telomerase. It is important to note that the effects of exercise vary depending on the type, intensity, frequency, and duration of exercise as well as on the individual's characteristics; therefore, the development of personalized exercise programs is essential. PMID- 26823957 TI - Complete genome sequence and genomic characterization of Microcystis panniformis FACHB 1757 by third-generation sequencing. AB - The cyanobacterial genus Microcystis is well known as the main group that forms harmful blooms in water. A strain of Microcystis, M. panniformis FACHB1757, was isolated from Meiliang Bay of Lake Taihu in August 2011. The whole genome was sequenced using PacBio RS II sequencer with 48-fold coverage. The complete genome sequence with no gaps contained a 5,686,839 bp chromosome and a 38,683 bp plasmid, which coded for 6,519 and 49 proteins, respectively. Comparison with strains of M. aeruginosa and some other water bloom-forming cyanobacterial species revealed large-scale structure rearrangement and length variation at the genome level along with 36 genomic islands annotated genome-wide, which demonstrates high plasticity of the M. panniformis FACHB1757 genome and reveals that Microcystis has a flexible genome evolution. PMID- 26823956 TI - Oxidative Stress and Carbonyl Lesions in Ulcerative Colitis and Associated Colorectal Cancer. AB - Oxidative stress has long been known as a pathogenic factor of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC), but the effects of secondary carbonyl lesions receive less emphasis. In inflammatory conditions, reactive oxygen species (ROS), such as superoxide anion free radical (O2 (?-)), hydrogen peroxide (H2O2), and hydroxyl radical (HO(?)), are produced at high levels and accumulated to cause oxidative stress (OS). In oxidative status, accumulated ROS can cause protein dysfunction and DNA damage, leading to gene mutations and cell death. Accumulated ROS could also act as chemical messengers to activate signaling pathways, such as NF-kappaB and p38 MAPK, to affect cell proliferation, differentiation, and apoptosis. More importantly, electrophilic carbonyl compounds produced by lipid peroxidation may function as secondary pathogenic factors, causing further protein and membrane lesions. This may in turn exaggerate oxidative stress, forming a vicious cycle. Electrophilic carbonyls could also cause DNA mutations and breaks, driving malignant progression of UC. The secondary lesions caused by carbonyl compounds may be exceptionally important in the case of host carbonyl defensive system deficit, such as aldo-keto reductase 1B10 deficiency. This review article updates the current understanding of oxidative stress and carbonyl lesions in the development and progression of UC and CAC. PMID- 26823958 TI - Draft genome sequence for virulent and avirulent strains of Xanthomonas arboricola isolated from Prunus spp. in Spain. AB - Xanthomonas arboricola is a species in genus Xanthomonas which is mainly comprised of plant pathogens. Among the members of this taxon, X. arboricola pv. pruni, the causal agent of bacterial spot disease of stone fruits and almond, is distributed worldwide although it is considered a quarantine pathogen in the European Union. Herein, we report the draft genome sequence, the classification, the annotation and the sequence analyses of a virulent strain, IVIA 2626.1, and an avirulent strain, CITA 44, of X. arboricola associated with Prunus spp. The draft genome sequence of IVIA 2626.1 consists of 5,027,671 bp, 4,720 protein coding genes and 50 RNA encoding genes. The draft genome sequence of strain CITA 44 consists of 4,760,482 bp, 4,250 protein coding genes and 56 RNA coding genes. Initial comparative analyses reveals differences in the presence of structural and regulatory components of the type IV pilus, the type III secretion system, the type III effectors as well as variations in the number of the type IV secretion systems. The genome sequence data for these strains will facilitate the development of molecular diagnostics protocols that differentiate virulent and avirulent strains. In addition, comparative genome analysis will provide insights into the plant-pathogen interaction during the bacterial spot disease process. PMID- 26823959 TI - Complete genome sequence and characterization of avian pathogenic Escherichia coli field isolate ACN001. AB - Avian pathogenic Escherichia coli is an important etiological agent of avian colibacillosis, which manifests as respiratory, hematogenous, meningitic, and enteric infections in poultry. It is also a potential zoonotic threat to human health. The diverse genomes of APEC strains largely hinder disease prevention and control measures. In the current study, pyrosequencing was used to analyze and characterize APEC strain ACN001 (= CCTCC 2015182(T) = DSMZ 29979(T)), which was isolated from the liver of a diseased chicken in China in 2010. Strain ACN001 belongs to extraintestinal pathogenic E. coli phylogenetic group B1, and was highly virulent in chicken and mouse models. Whole genome analysis showed that it consists of six different plasmids along with a circular chromosome of 4,936,576 bp, comprising 4,794 protein-coding genes, 108 RNA genes, and 51 pseudogenes, with an average G + C content of 50.56 %. As well as 237 coding sequences, we identified 39 insertion sequences, 12 predicated genomic islands, 8 prophage related sequences, and 2 clustered regularly interspaced short palindromic repeats regions on the chromosome, suggesting the possible occurrence of horizontal gene transfer in this strain. In addition, most of the virulence and antibiotic resistance genes were located on the plasmids, which would assist in the distribution of pathogenicity and multidrug resistance elements among E. coli populations. Together, the information provided here on APEC isolate ACN001 will assist in future study of APEC strains, and aid in the development of control measures. PMID- 26823960 TI - The PI3Kdelta inhibitor idelalisib suppresses liver and lung cellular respiration. AB - Idelalisib (an inhibitor of phosphatidylinositol-3-kinase-delta) is approved for treatment of B-cell malignancies, with a Boxed Warning concerning potentially fatal hepatic, lung, and intestinal toxicities. The mechanisms of these tissue specific adverse events have yet to be elucidated. This in vitro study investigated whether these effects could be attributed, at least in part, to altered cellular bioenergetics. A phosphorescence analyzer was used to measure cellular mitochondrial O2 consumption (kc , uM O2 min(-1) mg(-1)) in C57BL/6 mouse organs in the presence of 10 uM idelalisib or dimethyl-sulfoxide. Idelalisib significantly reduced the rate of cellular respiration in liver and lung fragments by 20% and 27%, respectively. Respiration in intestinal, thymic, and kidney fragments was unaffected. Idelalisib did not alter respiratory chain activities in mitochondria isolated from the liver and did not induce hepatocyte death. Thus, the drug mildly lowers liver and lung cellular respiration, an effect that may contribute to toxicities observed in these organs. PMID- 26823961 TI - Age-related attenuation of parasympathetic control of the heart in mice. AB - The autonomic nervous system maintains homeostasis through the balance of the sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS). Especially evident in the heart, maintenance of this balance is important for the control of heart rate, conduction, and contractility. It is known that aging, similar to various cardiovascular diseases, results in an increase in SNS activity and a decrease in PSNS activity, which may contribute to age-related cardiac dysfunction and remodeling. Intracardiac ganglia relay and integrate the PSNS signals to the heart. Therefore, this study investigated whether altered function of intracardiac ganglia is involved in age-related parasympathetic dysfunction and the potential role of the major cholinergic components of intracardiac ganglionic transmission in the process. This study utilized two age groups of mice, the younger mice at 1-2.5 months of age, and the older mice at 11 12 months of age. The results show that the older mice exhibit diminishment of both baroreflex sensitivity and response to rostral-severed vagal stimulation but preserved response to administration of muscarinic acetylcholine receptor agonist, bethanechol. Analysis of whole atrial lysate revealed significant diminishments in choline acetyltransferase (ChAT) and the upper band of vesicular acetylcholine transporter (VAchT). In contrast, the upper band of the high affinity choline transporter (CHT) was significantly upregulated in the older group. Further analysis showed that the soluble but not insoluble fraction of CHT protein is significantly increased in the older group. This implicates a potential reduction of acetylcholine synthesis and/or release and an improper compensatory change of CHT may be responsible for the PSNS dysfunction exhibited in this model. PMID- 26823962 TI - Chronic intermittent voluntary alcohol drinking induces hyperalgesia in Sprague Dawley rats. AB - The mechanisms of hyperalgesia in alcoholics are not completely clear, and the development of animal models would therefore be necessary in investigating the underlying changes. Several studies including our own have demonstrated that the intermittent access to 20% ethanol two-bottle choice procedure (IA2BC) promotes escalation of drinking, and induces physical dependence in the Sprague-Dawley (SD) rat, one of the strains most commonly used in preclinical alcohol research. In this study, we investigated whether the IA2BC procedure could produce hyperalgesia in SD rats. We show here that, the SD rats in the IA2BC procedure significantly escalated their drinking within 8 weeks, which is consistent with other studies. Starting from 8 weeks of repeated chronic drinking, the mechanical and thermal sensitivity was significantly increased. During withdrawal, there were noticeable physical dependence signs, including tail stiffness and lower limb flexion, which started at 4 hours and lasted for more than 3 days after ethanol removal. Importantly, during withdrawal, the mechanical and thermal sensitivity was further increased, which started at 12 hours and lasted for more than seven days after ethanol removal. These results suggest that utilizing the SD rat under the IA2BC procedure could be a useful animal model with heuristic value for exploring the mechanisms underlying hyperalgesia induced by chronic alcohol abuse. PMID- 26823963 TI - Effects of electroacupuncture on cognitive function in rats with Parkinson's disease. AB - This study was designed to illustrate the effects of electroacupuncture on cognitive function in rats with Parkinson's disease (PD). The PD model was established by injecting 6-OHDA into the rat brain. Rats with PD were then subjected to electroacupuncture and levodopa treatment for 2 weeks. The level of choline acetyltransferase (ChAT) activity in rat brain homogenates was assessed, for the cerebral cholinergic system is a major chemical pathway consisting of cognitive functions. Immunohistochemistry was applied to observe ChAT expression in the rat hippocampus and corpus striatum. The effects of electroacupuncture on cognitive function were comprehensively assessed in PD rats using Y-maze test. Compared with model control group, electroacupuncture group were apparently improved in learning & memory abilities, and ChAT activity was elevated, and apoptosis was reduced in the rat hippocampus and corpus striatum. No significant differences in learning & memory abilities and ChAT activity were detected between electroacupuncture and levodopa groups. Electroacupuncture remarkably improved cognition in PD rats, and its mechanisms are possibly associated with protecting cholinergic neurons in the central nervous system and elevating ChAT activity, and also might suitable dosage of levodopa protect physiologically the cognitive function in PD rats. PMID- 26823964 TI - Cross interaction of melanocortinergic and dopaminergic systems in neural modulation. AB - Melanocortinergic and dopaminergic systems are widely distributed in the CNS and have been established as a crucial regulatory component in diverse physiological functions. The pharmacology of both melanocortinergic and dopaminergic systems including their individual receptors, signaling mechanisms, agonists and antagonists has been extensively studied. Several lines of evidence showed that there existed a cross interaction between the receptors of melanocortinergic and dopaminergic systems. The data available at present had expanded our understanding of melanocortinergic and dopaminergic system interaction in neural modulation, which will be main discussed in this paper. PMID- 26823965 TI - Meta-analysis of the efficacy of lansoprazole and omeprazole for the treatment of H.pylori-associated duodenal ulcer. AB - OBJECTIVE: To conduct a systematic evaluation of the efficacy of lansoprazole and omeprazole for the treatment of Helicobacter pylori-associated duodenal ulcer. METHODS: Online databases, including CHKD, VIP, China Info, the National Digital Library of China, Google Scholar, PubMed, Lippincott Williams & Wilkins, and Wiley Online Library were searched for related studies. The quality of the studies was evaluated in accordance with the Cochrane Handbook for Systematic Reviews of Interventions, and relevant information was extracted from them. The studies were subjected to meta-analysis using RevMan5.3 software, and qualitative analysis was performed for studies, in which the data could not be merged. RESULTS: A total of nine randomized controlled trials (RCTs) were included, all of which presented the possibility of bias. Meta-analysis showed no significant differences between patients treated with lansoprazole combinations and omeprazole combinations in terms of DU healing rate (RR = 1.04, 95% CI = 0.99~1.09, P = 0.93). There were significant differences between those treated by lansoprazole combination and omeprazole combination in terms of HP eradication rate (RR = 1.09, 95% CI = 1.01~1.18, P = 0.04), and there was no serious adverse reaction during the treatment process for both lansoprazole and omeprazole. CONCLUSION: Lansoprazole and omeprazole exhibit similar efficacy in the treatment of Helicobacter pylori associated duodenal ulcers. PMID- 26823966 TI - Altered functional connectivity of the amygdaloid input nuclei in adolescents and young adults with autism spectrum disorder: a resting state fMRI study. AB - BACKGROUND: Amygdala dysfunction is hypothesized to underlie the social deficits observed in autism spectrum disorders (ASD). However, the neurobiological basis of this hypothesis is underspecified because it is unknown whether ASD relates to abnormalities of the amygdaloid input or output nuclei. Here, we investigated the functional connectivity of the amygdaloid social-perceptual input nuclei and emotion-regulation output nuclei in ASD versus controls. METHODS: We collected resting state functional magnetic resonance imaging (fMRI) data, tailored to provide optimal sensitivity in the amygdala as well as the neocortex, in 20 adolescents and young adults with ASD and 25 matched controls. We performed a regular correlation analysis between the entire amygdala (EA) and the whole brain and used a partial correlation analysis to investigate whole-brain functional connectivity uniquely related to each of the amygdaloid subregions. RESULTS: Between-group comparison of regular EA correlations showed significantly reduced connectivity in visuospatial and superior parietal areas in ASD compared to controls. Partial correlation analysis revealed that this effect was driven by the left superficial and right laterobasal input subregions, but not the centromedial output nuclei. CONCLUSIONS: These results indicate reduced connectivity of specifically the amygdaloid sensory input channels in ASD, suggesting that abnormal amygdalo-cortical connectivity can be traced down to the socio-perceptual pathways. PMID- 26823967 TI - Sexually dimorphic effects of early life stress in rat pups on urinary bladder detrusor muscle contractility in adulthood. AB - BACKGROUND: Painful bladder syndrome/interstitial cystitis (PBS/IC) is a chronic disorder that is commonly seen in women who report a history of adversity in early life. Here, we test the hypothesis that early life stress (ELS) induces sexually dimorphic abnormalities in urinary bladder smooth muscle function in adulthood. METHODS: Male and female rat pups were conditioned on postnatal (PN) days 8-12 with either a "predictable or "unpredictable" odor-shock, or odor only control treatment. In adulthood, urinary bladder function was assessed in vivo via urine spot analysis and in vitro via contractile responses to electrical field stimulation (EFS) and membrane depolarization with potassium chloride (KCl). RESULTS: In adulthood, we found that female rats exposed to unpredictable ELS showed a significant (p < 0.05) increase in urine voiding volume compared to predictable ELS or controls. We also found that detrusor muscle contractile responses to EFS were significantly (p < 0.001) decreased following unpredictable ELS in adult female rats compared to the predictable ELS or controls. In male rats exposed to ELS, there was no difference in voiding volume or EFS-induced contractility between groups. In adulthood, the myogenic smooth muscle response to KCl was not significantly different between groups. Histological analysis from adult female and male rats revealed no differences in the appearance of the urinary bladder in rats exposed to ELS. CONCLUSIONS: In summary, our findings provide evidence to support abnormalities in the nerve-mediated contractile responses of the detrusor smooth muscle in adult female rats following ELS. We speculate that these sexually dimorphic alterations in urinary bladder function may account, at least in part, for the female predominance of PBS/IC. PMID- 26823968 TI - High-fat diet impairs spatial memory and hippocampal intrinsic excitability and sex-dependently alters circulating insulin and hippocampal insulin sensitivity. AB - BACKGROUND: High-fat diets promoting obesity/type-2 diabetes can impair physiology and cognitive performance, although sex-dependent comparisons of these impairments are rarely made. Transient reductions in Ca(2+)-dependent afterhyperpolarizations (AHPs) occur during memory consolidation, enhancing intrinsic excitability of hippocampal CA1 pyramidal neurons. In rats fed standard diets, insulin can enhance memory and reduce amplitude and duration of AHPs. METHODS: Effects of chronic high-fat diet (HFD) on memory, circulating insulin, and neuronal physiology were compared between young adult male and female Long Evans rats. Rats fed for 12 weeks (from weaning) a HFD or a control diet (CD) were then tested in vivo prior to in vitro recordings from CA1 pyramidal neurons. RESULTS: The HFD significantly impaired spatial memory in both males and females. Significant sex differences occurred in circulating insulin and in the insulin sensitivity of hippocampal neurons. Circulating insulin significantly increased in HFD males but decreased in HFD females. While the HFD significantly reduced hippocampal intrinsic excitability in both sexes, CA1 neurons from HFD females remained insulin-sensitive but those from HFD males became insulin-insensitive. CONCLUSIONS: Findings consistent with these have been characterized previously in HFD or senescent males, but the effects observed here in young females are unique. Loss of CA1 neuronal excitability, and sex-dependent loss of insulin sensitivity, can have significant cognitive consequences, over both the short term and the life span. These findings highlight needs for more research into sex dependent differences, relating systemic and neural plasticity mechanisms in metabolic disorders. PMID- 26823969 TI - DNA-binding sequence specificity of DUX4. AB - BACKGROUND: Misexpression of the double homeodomain transcription factor DUX4 results in facioscapulohumeral muscular dystrophy (FSHD). A DNA-binding consensus with two tandem TAAT motifs based on chromatin IP peaks has been discovered; however, the consensus has multiple variations (flavors) of unknown relative activity. In addition, not all peaks have this consensus, and the Pitx1 promoter, the first DUX4 target sequence mooted, has a different TAAT-rich sequence. Furthermore, it is not known whether and to what extent deviations from the consensus affect DNA-binding affinity and transcriptional activation potential. RESULTS: Here, we take both unbiased and consensus sequence-driven approaches to determine the DNA-binding specificity of DUX4 and its tolerance to mismatches at each site within its consensus sequence. We discover that the best binding and the greatest transcriptional activation are observed when the two TAAT motifs are separated by a C residue. The second TAAT motif in the consensus sequence is actually (T/C)AAT. We find that a T is preferred here. DUX4 has no transcriptional activity on "half-sites", i.e., those bearing only a single TAAT motif. We further find that DUX4 does not bind to the TAATTA motif in the Pitx1 promoter, that Pitx1 sequences have no competitive band shift activity, and that the Pitx1 sequence is transcriptionally inactive, calling into question PITX1 as a DUX4 target gene. Finally, by multimerizing binding sites, we find that DUX4 transcriptional activation demonstrates tremendous synergy and that at low DNA concentrations, at least two motifs are necessary to detect a transcriptional response. CONCLUSIONS: These studies illuminate the DNA-binding sequence preferences of DUX4. PMID- 26823970 TI - Conservative care with or without manipulative therapy in the management of back and neck pain in Danish children aged 9-15. Study protocol for a randomized controlled trial. AB - BACKGROUND: Complaints in the musculoskeletal system often start early in life and back and neck pain in children are well-established predictors for similar problems in adulthood. Despite lack of evidence of effectiveness, manipulative therapy is one of the most commonly used treatment modalities for back and neck pain in children. The primary objective of this study is to evaluate the effectiveness of manipulative therapy when added to an approach consisting of manual soft tissue treatment, exercises and advice as needed, in children aged 9 15 complaining of back and neck pain. METHOD: The project is nested in the Childhood Health, Activity and Motor Performance School Study, which includes around 1200 children aged 9-15, who were all invited to participate in this randomized controlled trial in case they experienced back and/or neck pain during the two year inclusion period. Parents received text messages (SMS) on a weekly basis inquiring about the child's musculoskeletal pain. If pain was reported, the child was evaluated for inclusion into the trial and, if eligible, randomized into one of two intervention groups:Pragmatic advice, manual soft tissue treatment and exercisesThe above plus manipulative therapy By the end of data collection 237 children were included in the study. The primary outcome measure is number of recurrences of back and neck pain during the follow-up period (3-27 months). Secondary outcome measures are average duration of complaint time for each episode, total duration of complaint time, global perceived effect after two weeks, and change in pain intensity after 2 weeks. Baseline information includes quality of life, expectations to treatment, expectations to future course, age, gender, social class and physical education at school. DISCUSSION: For most common non-traumatic musculoskeletal complaints no standardized and evidence based treatment strategy exists. We want to evaluate the effectiveness of manipulative therapy in addition to an approach consisting of manual soft tissue treatment, exercises and advice as needed, in children aged 9-15 complaining of back and neck pain. To our knowledge this is the first large scale randomized controlled trial investigating the effectiveness of commonly used treatments for back and neck pain in children. TRIAL REGISTRATION: ClinicalTrials NCT01504698. PMID- 26823971 TI - The role of CYP3A5 polymorphism and dose adjustments following conversion of twice-daily to once-daily tacrolimus in renal transplant recipients. AB - BACKGROUND: Tacrolimus is available as twice-daily Prograf(r) (Tac-BID) and the once-daily formulation, Advagraf(r) (Tac-OD). Although therapeutically equivalent, some transplant recipients require dose adjustments to achieve similar tacrolimus trough concentrations [Tac C0] after conversion between formulations. Tacrolimus is primarily metabolized by cytochrome P450 3A5 (CYP3A5). We sought to determine whether genetic polymorphisms in the CYP3A5 enzyme; CYP3A5 *1/*1 and CYP3A5 *1/*3 (expressers) compared to CYP3A5 *3/*3 (non expressers) could account for discrepancies in dose requirements following conversion from Tac-BID to Tac-OD. METHODS: A cohort of 60 renal transplant recipients (RTR) from our larger conversion study of 496 patients underwent additional testing for CY3A5 genetic polymorphisms. Analysis included demographics, tac dosing and [Tac C0] pre- and post-conversion and dosing changes relative to CYP3A5 genotypes. CYP3A5 genetic polymorphisms were identified through analysis of genomic DNA. RESULTS: Conversion from tac bid to tac OD in this cohort required a mean (SD) dose increase from 3.1 (1.0) mg/day to 3.8 (1.3) mg/day (p = 0.007), to achieve similar [Tac C0]. The *1/*3 expresser group required a greater percentage dose adjustment (56.7 %) in converting from Tac-BID to Tac-OD as compared to the *3/*3 non-expresser group (26.6 %). Similar findings were observed with the both expresser groups combined (*1/*1 &*1/*3). The expressers were significantly more highly represented in the East Asian cohort. CONCLUSIONS: The CYP3A5 expresser polymorphism necessitates an increase in dosing upon conversion from Tac-BID to Tac-OD, with the expresser genotypes contributing significantly to this finding. Given the variability in frequency of CYP3A5 genotypes in various ethnic groups, future studies should account for both isoenzyme polymorphism and ethnicity in optimizing dosing requirements. TRIAL REGISTRATION: Clinical trials.gov identifier: NCT01884480. PMID- 26823972 TI - Genomes and virulence difference between two physiological races of Phytophthora nicotianae. AB - BACKGROUND: Black shank is a severe plant disease caused by the soil-borne pathogen Phytophthora nicotianae. Two physiological races of P. nicotianae, races 0 and 1, are predominantly observed in cultivated tobacco fields around the world. Race 0 has been reported to be more aggressive, having a shorter incubation period, and causing worse root rot symptoms, while race 1 causes more severe necrosis. The molecular mechanisms underlying the difference in virulence between race 0 and 1 remain elusive. FINDINGS: We assembled and annotated the genomes of P. nicotianae races 0 and 1, which were obtained by a combination of PacBio single-molecular real-time sequencing and second-generation sequencing (both HiSeq and MiSeq platforms). Gene family analysis revealed a highly expanded ATP-binding cassette transporter gene family in P. nicotianae. Specifically, more RxLR effector genes were found in the genome of race 0 than in that of race 1. In addition, RxLR effector genes were found to be mainly distributed in gene-sparse, repeat-rich regions of the P. nicotianae genome. CONCLUSIONS: These results provide not only high quality reference genomes of P. nicotianae, but also insights into the infection mechanisms of P. nicotianae and its co-evolution with the host plant. They also reveal insights into the difference in virulence between the two physiological races. PMID- 26823973 TI - Species-level resolution of 16S rRNA gene amplicons sequenced through the MinIONTM portable nanopore sequencer. AB - BACKGROUND: The miniaturised and portable DNA sequencer MinIONTM has been released to the scientific community within the framework of an early access programme to evaluate its application for a wide variety of genetic approaches. This technology has demonstrated great potential, especially in genome-wide analyses. In this study, we tested the ability of the MinIONTM system to perform amplicon sequencing in order to design new approaches to study microbial diversity using nearly full-length 16S rDNA sequences. RESULTS: Using R7.3 chemistry, we generated more than 3.8 million events (nt) during a single sequencing run. These data were sufficient to reconstruct more than 90 % of the 16S rRNA gene sequences for 20 different species present in a mock reference community. After read mapping and 16S rRNA gene assembly, consensus sequences and 2d reads were recovered to assign taxonomic classification down to the species level. Additionally, we were able to measure the relative abundance of all the species present in a mock community and detected a biased species distribution originating from the PCR reaction using 'universal' primers. CONCLUSIONS: Although nanopore-based sequencing produces reads with lower per-base accuracy compared with other platforms, the MinIONTM DNA sequencer is valuable for both high taxonomic resolution and microbial diversity analysis. Improvements in nanopore chemistry, such as minimising base-calling errors and the nucleotide bias reported here for 16S amplicon sequencing, will further deliver more reliable information that is useful for the specific detection of microbial species and strains in complex ecosystems. PMID- 26823974 TI - Draft genome of the Chinese mitten crab, Eriocheir sinensis. AB - BACKGROUND: The Chinese mitten crab, Eriocheir sinensis, is one of the most studied and economically important crustaceans in China. Its transition from a swimming to a crawling method of movement during early development, anadromous migration during growth, and catadromous migration during breeding have been attractive features for research. However, knowledge of the underlying molecular mechanisms that regulate these processes is still very limited. FINDINGS: A total of 258.8 gigabases (Gb) of raw reads from whole-genome sequencing of the crab were generated by the Illumina HiSeq2000 platform. The final genome assembly (1.12 Gb), about 67.5 % of the estimated genome size (1.66 Gb), is composed of 17,553 scaffolds (>2 kb) with an N50 of 224 kb. We identified 14,436 genes using AUGUSTUS, of which 7,549 were shown to have significant supporting evidence using the GLEAN pipeline. This gene number is much greater than that of the horseshoe crab, and the annotation completeness, as evaluated by CEGMA, reached 66.9 %. CONCLUSIONS: We report the first genome sequencing, assembly, and annotation of the Chinese mitten crab. The assembled draft genome will provide a valuable resource for the study of essential developmental processes and genetic determination of important traits of the Chinese mitten crab, and also for investigating crustacean evolution. PMID- 26823975 TI - De novo construction of an expanded transcriptome assembly for the western tarnished plant bug, Lygus hesperus. AB - BACKGROUND: The plant bug Lygus hesperus Knight is a polyphagous pest of many economically important crops. Despite its pest status, little is known about the molecular mechanisms responsible for much of the biology of this species. Earlier Lygus transcriptome assemblies were limited by low read depth, or because they focused on specific conditions. To generate a more comprehensive transcriptome, we supplemented previous datasets with new reads corresponding to specific tissues (heads, antennae, and male reproductive tissues). This transcriptome augments current Lygus molecular resources and provides the foundational knowledge critical for future comparative studies. FINDINGS: An expanded, Trinity based de novo transcriptome assembly for L. hesperus was generated using previously published whole body Illumina data, supplemented with 293 million bp of new raw sequencing data corresponding to five tissue-specific cDNA libraries and 11 Illumina sequencing runs. The updated transcriptome consists of 22,022 transcripts (average length of 2075 nt), 62 % of which contain complete open reading frames. Significant coverage of the BUSCO (benchmarking universal single copy orthologs) dataset and robust metrics indicate that the transcriptome is a quality assembly with a high degree of completeness. Initial assessment of the new assembly's utility revealed that the length and abundance of transcripts predicted to regulate insect physiology and chemosensation have improved, compared with previous L. hesperus assemblies. CONCLUSIONS: This transcriptome represents a significant expansion of Lygus transcriptome data, and improves foundational knowledge about the molecular mechanisms underlying L. hesperus biology. The dataset is publically available in NCBI and GigaDB as a resource for researchers. PMID- 26823976 TI - Dietary intake patterns and nutritional status of women of reproductive age in Nepal: findings from a health survey. AB - BACKGROUND: Improper dietary intake pattern in women of reproductive age in Nepal has resulted in the deficiency of essential nutrients. Adequate nutritional status and proper dietary intake pattern of women improves maternal and child health. The objective of this study was to assess the nutritional status and dietary intake pattern among the women and associated factors. METHODS: Data collection at households and health check-up camps were conducted in selected Village Development Committees of nine districts in three ecological regions (Mountain, Hill and Terai) of Nepal from September 2011 to August 2012. Women of reproductive age (15 to 49 years) were the study subjects. At the household interview, structured questionnaires were used to obtain information on socio demographic characteristics, anthropometric measurements, dietary intake pattern, consumption of junk foods, animal rearing, agricultural products, possession of kitchen garden, pregnancy status and anemia. Dietary intake pattern was determined by information collected through the structured questionnaires comprising of food items-cereals, pulses/legumes, vegetables, meat, fruits and milk and milk products. Health check-up camps were conducted in the local health facilities where qualified doctors, nurses and laboratory technicians performed physical examination of the women, confirmed their pregnancy and conducted hematocrit tests. The data was entered and analyzed using SPSS. RESULTS: Altogether 21,111 women were interviewed. More than a quarter of the women in Terai were malnourished as indicated by low body mass index (BMI < 18.5 Kg/m(2)). Among the dietary intake pattern, the majority of women consumed cereals at least once a day in all three ecological regions. The majority of women in Mountain consumed pulses/legumes thrice a week. In Terai, the majority of women consumed vegetables thrice a week. In all three ecological regions, the majority of women consumed meat and meat products and fruits once a week. About thirty percent of women consumed milk and milk products once a day in all three ecological regions. The non-use of iodized salt by Terai women was the highest (5.3 %, n = 303). In all the ecological regions, cereals and vegetables were produced in the majority of the participants' households in comparison of fruits, poultry and goat/sheep. The women of age 15 to 24 years were 2.7 times more likely to be malnourished than women of 35 to 49 years age (aOR = 2.7, CI = 2.5,3.0). The unemployed women had nearly two times more chances of being malnourished than women doing manual work (aOR = 1.9, 95 % CI = 1.5,2.2). In Terai, women were five times more likely to be malnourished (aOR = 0.2, CI = 0.1,0.2) and 20 times more likely to be anemic (aOR = 0.05, CI = 0.04,0.07) than women in Mountain. The pregnant women were five times more likely to be anemic than non-pregnant women (aOR = 0.2, CI = 0.2,0.3). CONCLUSIONS: The nutritional status of women of reproductive age is still poor especially in Terai and the dietary intake pattern is not adequate. It suggests improving nutritional status and feeding habits especially intake of meat, fruits and vegetables focusing on reproductive aged women. PMID- 26823977 TI - The assessment of new drugs for asthma and COPD: a Delphi study examining the perspectives of Italian payers and clinicians. AB - BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are disorders of the lungs characterized by airflow obstruction, inflammation and tissue remodeling. Management of patients with these diseases is complex and the improvement of diagnostic-therapeutic strategies represents a critical challenge for the healthcare system. In this context, investigating the criteria and information needed for an appropriate and effective evaluation of incoming treatment options is crucial to ensure that clinicians and policy-makers are provided with the best available evidence to make decisions aimed at improving patient outcomes. Therefore, the objective of this study was to investigate the degree of agreement among Health Technology Assessment (HTA) experts on issues crucial to the evaluation of new drugs for asthma and COPD and to appropriately manage the clinical pathway for patients. METHOD: This research was conducted using an e-Delphi technique organized in three subsequent rounds and involving a panel of ten experts (six regional and local payers and four clinicians). Panelists were asked to comment in written form on a set of statements, explaining qualitatively the extent to which they agreed or disagreed with the assertions. Statements were subsequently modified and resubmitted for assessment. RESULTS: Panelists expressed their opinions during each round and, after round III, a consensus document was finalized. The degree of consensus was high among experts and concerned five main topics: (a) the need to address current unmet needs of patients with asthma or COPD, (b) the importance of further studies and real-life information in the evaluation of treatments, (c) existing evidence and evidence needed to assess drugs, (d) critical issues in obtaining a positive evaluation from regional and local authorities for new treatments to be included in regional formularies and to have an important place in therapeutic categories, and (e) the major obstacles to the appropriate administration of drugs and management of patients. CONCLUSION: The final document highlights that no proof of difference among drugs exists, that evidence on final endpoints (and particularly on mortality) should be strengthened and that actions regarding risk factors, appropriate diagnosis, patient staging and adherence to therapy are particularly important for a better clinical management. PMID- 26823978 TI - A panel of glycoproteins as candidate biomarkers for early diagnosis and treatment evaluation of B-cell acute lymphoblastic leukemia. AB - BACKGROUND: Acute lymphoblastic leukemia is the most common malignant cancer in childhood. The signs and symptoms of childhood cancer are difficult to recognize, as it is not the first diagnosis to be considered for nonspecific complaints, leading to potential uncertainty in diagnosis. The aim of this study was to perform proteomic analysis of serum from pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) to identify candidate biomarker proteins, for use in early diagnosis and evaluation of treatment. METHODS: Serum samples were obtained from ten patients at the time of diagnosis (B-ALL group) and after induction therapy (AIT group). Sera from healthy children were used as controls (Control group). The samples were subjected to immunodepletion, affinity chromatography with alpha-d-galactose-binding lectin (from Artocarpus incisa seeds) immobilized on a Sepharose(TM) 4B gel, concentration, and digestion for subsequent analysis with nano-UPLC tandem nano-ESI-MS(E). The program Expression (E) was used to quantify differences in protein expression between groups. RESULTS: A total of 96 proteins were identified. Leucine-rich alpha-2 glycoprotein 1 (LRG1), Clusterin (CLU), thrombin (F2), heparin cofactor II (SERPIND1), alpha-2-macroglobulin (A2M), alpha-2-antiplasmin (SERPINF2), Alpha-1 antitrypsin (SERPINA1), Complement factor B (CFB) and Complement C3 (C3) were identified as candidate biomarkers for early diagnosis of B-ALL, as they were upregulated in the B-ALL group relative to the control and AIT groups. Expression levels of the candidate biomarkers did not differ significantly between the AIT and control groups, providing further evidence that the candidate biomarkers are present only in the disease state, as all patients achieved complete remission after treatment. CONCLUSION: A panel of protein biomarker candidates has been developed for pre-diagnosis of B-ALL and also provided information that would indicate a favorable response to treatment after induction therapy. PMID- 26823979 TI - Low serum insulin-like growth factor-1 in patients with erectile dysfunction. AB - OBJECTIVE: Endothelial dysfunction and microvascular damage play a crurical role in the pathogenesis of erectile dysfunction (ED). Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. IGF-1 is an important mediator of cell growth, differentiation and transformation in various tissues. The purpose of the current study was to determine the association between IGF-1 levels and ED. MATERIALS AND METHODS: All men were evaluated for ED and divided into two groups: 80 patients suffering from ED for > 1 year and 80 subjects without ED were enrolled as a control group in this study. Diagnosis of ED was based on the International Index of Erectile Function Score 5. IGF-1 levels were measured in serum by an automated chemiluminescence immunoassay. The relationship between IGF-1 levels and ED scores in patients was statistically evaluated. RESULTS: The mean age of patients in ED group was 60.4 +/- 11.3 years and 55.4 +/- 9.6 in control group. The plasma IGF-1 levels were significantly lower in ED than in control group (96.5 +/- 38.3 and 132.5 +/- 53.3 ng/ mL, respectively, P < 0.001). The IGF-1 levels were positively correlated with ED score (r = 0.623, P < 0.01). CONCLUSION: In this study serum IGF-1 levels were found to be associated with endothelial dysfunction that predicts ED. Serum IGF-1 level appears to be a specific predictor of ED, and it might be used in early prediction of ED in male population. PMID- 26823980 TI - The Association of Endothelin-1 with Markers of Arterial Stiffness in Black South African Women: The SABPA Study. AB - Background. Limited data exist regarding endothelin-1 (ET-1), a vasoactive contributor in vascular tone, in a population subjected to early vascular deterioration. We compared ET-1 levels and explored its association with markers of arterial stiffness in black and white South Africans. Methodology. This cross sectional substudy included 195 black (men: n = 99; women: n = 95) and 197 white (men: n = 99; women: n = 98) South Africans. Serum ET-1 levels were measured as well as markers of arterial stiffness (blood pressure, pulse wave velocity, and arterial compliance). ET-1 levels were higher in black men and white women compared to their counterparts after adjusting for C-reactive protein. In both single and partial (adjusting for body mass index and gamma glutamyl transferase) regression analyses ET-1 correlated with age, interleukin-6, high density lipoprotein cholesterol, systolic blood pressure, pulse pressure, and pulse wave velocity in black women. In multivariate regression analyses the independent association of ET-1 with systolic blood pressure (Adj. R (2) = 0.13; beta = 0.28, p < 0.01) and pulse pressure (Adj. R (2) = 0.11; beta = 0.27, p < 0.01) was confirmed in black women only. ET-1 additionally associated with interleukin-6 in black women (p < 0.01). Conclusion. Our result suggests that ET-1 and its link with subclinical arteriosclerosis are potentially driven by low-grade inflammation as depicted by the association with interleukin-6 in the black female cohort. PMID- 26823981 TI - Lipid Lowering Effects of Hydroalcoholic Extract of Anethum graveolens L. and Dill Tablet in High Cholesterol Fed Hamsters. AB - Objective. This study was aimed to determine the effect of Anethum graveolens extract and Anethum graveolens (dill) tablet on lipid profile, liver enzymes, and gene expression and enzymatic activity of HMG-CoA reductase in high cholesterol fed hamsters. Materials and Methods. Golden Syrian male hamsters (130 +/- 10 g) were randomly divided into 6 groups (n = 6) and received daily the following: group 1 received chow + 2% cholesterol + 0.5% cholic acid (HCD), groups 2 and 3 received HCD diet plus 100 and 200 mg/kg hydroalcoholic extract of dill, respectively, and groups 4 and 5 received HCD diet plus 100 and 200 mg/kg dill tablet, respectively. Group 6 received only chow. After 1 month feeding serum biochemical factors were determined. HMG-CoA reductase mRNA level was measured (real-time PCR) and its activity was determined spectrophotometrically. Results. Compared with hypercholesterolemic group 1, lipid profile, blood glucose, and liver enzymes significantly decreased in all dill tablet or dill extract treated groups (p < 0.05). The changes in HMG-CoA reductase gene expression level and enzyme activity significantly reduced in animals that received 200 mg/kg of extract or tablet. Conclusion. Dill extract and dill tablet showed potential hypocholesterolemic properties in hamsters by inhibition of HMG-CoA reductase activity. PMID- 26823982 TI - Rapid Progression of Coronary Atherosclerosis: A Review. AB - Atherosclerosis is chronic disease, the prevalence of which has increased steadily as the population ages. Vascular injury is believed to be critical initiating event in pathogenesis of spontaneous atherosclerosis. Syndrome of accelerated atherosclerosis has been classically described in patients undergoing heart transplantation, coronary artery bypass graft, and percutaneous transluminal coronary angioplasty. In contrast to spontaneous atherosclerosis, denuding endothelial injury followed by thrombus formation and initial predominant smooth muscle cell proliferation is believed to be playing a significant role in accelerated atherosclerosis. There is no universal definition of rapid progression of atherosclerosis. However most studies describing the phenomenon have used the following definition: (i) > or = 10% diameter reduction of at least one preexisting stenosis > or = 50%, (ii) > or = 30% diameter reduction of a preexisting stenosis <50%, and (iii) progression of a lesion to total occlusion within few months. Recent studies have described the role of coronary vasospasm, human immunodeficiency virus, various inflammatory markers, and some genetic mutations as predictors of rapid progression of atherosclerosis. As research in the field of vascular biology continues, more factors are likely to be implicated in the pathogenesis of rapid progression of atherosclerosis. PMID- 26823983 TI - Neural Mechanisms Involved in Hypersensitive Hearing: Helping Children with ASD Who Are Overly Sensitive to Sounds. AB - Professionals working with children diagnosed with autism spectrum disorder (ASD) may find that these children are overly sensitive to sounds. These professionals are often concerned as to why children may have auditory hypersensitivities. This review article discusses the neural mechanisms identified underlying hypersensitive hearing in people. The authors focus on brain research to support the idea of the nonclassical auditory pathways being involved in connecting the auditory system with the emotional system of the brain. The authors also discuss brain mechanisms felt to be involved in auditory hypersensitivity. The authors conclude with a discussion of some treatments for hypersensitive hearing. These treatments include desensitization training and the use of listening therapies such as The Listening Program. PMID- 26823984 TI - Altered Local Spontaneous Brain Activity in Juvenile Myoclonic Epilepsy: A Preliminary Resting-State fMRI Study. AB - Purpose. The purpose of this study was to evaluate the regional synchronization of brain in patients with juvenile myoclonic epilepsy (JME). Methods. Resting state fMRI data were acquired from twenty-one patients with JME and twenty-two healthy subjects. Regional homogeneity (ReHo) was used to analyze the spontaneous activity in whole brain. Two-sample t-test was performed to detect the ReHo difference between two groups. Correlations between the ReHo values and features of seizures were calculated further. Key Findings. Compared with healthy controls, patients showed significantly increased ReHo in bilateral thalami and motor-related cortex regions and a substantial reduction of ReHo in cerebellum and occipitoparietal lobe. In addition, greater ReHo value in the left paracentral lobule was linked to the older age of onset in patients. Significance. These findings implicated the abnormality of thalamomotor cortical network in JME which were associated with the genesis and propagation of epileptiform activity. Moreover, our study supported that the local brain spontaneous activity is a potential tool to investigate the epileptic activity and provided important insights into understanding the pathophysiological mechanisms of JME. PMID- 26823985 TI - Neuromodulation of Attentional Control in Major Depression: A Pilot DeepTMS Study. AB - While Major Depressive Disorder (MDD) is primarily characterized by mood disturbances, impaired attentional control is increasingly identified as a critical feature of depression. Deep transcranial magnetic stimulation (deepTMS), a noninvasive neuromodulatory technique, can modulate neural activity and induce neuroplasticity changes in brain regions recruited by attentional processes. This study examined whether acute and long-term high-frequency repetitive deepTMS to the dorsolateral prefrontal cortex (DLPFC) can attenuate attentional deficits associated with MDD. Twenty-one MDD patients and 26 matched control subjects (CS) were administered the Beck Depression Inventory and the Sustained Attention to Response Task (SART) at baseline. MDD patients were readministered the SART and depressive assessments following a single session (n = 21) and after 4 weeks (n = 13) of high-frequency (20 Hz) repetitive deepTMS applied to the DLPFC. To control for the practice effect, CS (n = 26) were readministered the SART a further two times. The MDD group exhibited deficits in sustained attention and cognitive inhibition. Both acute and long-term high-frequency repetitive frontal deepTMS ameliorated sustained attention deficits in the MDD group. Improvement after acute deepTMS was related to attentional recovery after long-term deepTMS. Longer term improvement in sustained attention was not related to antidepressant effects of deepTMS treatment. PMID- 26823986 TI - Donor Cell Myeloid Sarcoma in an Umbilical Cord Transplant Patient: A Case Report and a Review of the Literature. AB - Donor cell leukemia (DCL) represents a rare complication of allogeneic transplantation. The precise incidence remains unclear, though it may be higher following umbilical cord blood transplants. Here, we present an unusual case of a patient with B-ALL who presented with a donor derived myeloid sarcoma of the heart following a double cord blood transplant. To our knowledge, it is the first case of sarcomatous or chloromatous presentation of DCL following a UCBT. PMID- 26823987 TI - Establishing a cellular FRET-based fluorescence plate reader assay to monitor proNGF-induced cross-linking of sortilin and the neurotrophin receptor p75(NTR). AB - Whereas the proform of the nerve growth factor (proNGF) is crucial for eliminating superfluous cells during neuronal development it also promotes apoptosis following brain trauma and neuronal injury. The apoptotic signal is elicited upon formation of a trimeric receptor complex also containing the vps10p domain receptor sortilin and the neurotrophin receptor p75(NTR). However, proNGF induced receptor complex formation has been difficult to directly assess other than by western blotting. We here describe a fluorescence resonance energy transfer (FRET) based fluorescence plate reader assay to monitor the interaction between fluorescently tagged sortilin and p75(NTR) in live cells. The method is based on a standard fluorescent plate reader found in many biochemical laboratories and the results are evaluated using a microscopy-based quantified sensitized acceptor emission FRET approach making use of a pair of FRET standard constructs. As a result, the effect of proNGF on the interaction between sortilin and p75(NTR) can be evaluated in live cells allowing for screening and selection of therapeutic compounds interfering with proNGF-induced cell death. PMID- 26823988 TI - A Cooperatively Controlled Robot for Ultrasound Monitoring of Radiation Therapy. AB - Image-guided radiation therapy (IGRT) involves two main procedures, performed in different rooms on different days: (1) treatment planning in the simulator room on the first day, and (2) radiotherapy in the linear accelerator room over multiple subsequent days. Both the simulator and the linear accelerator include CT imaging capabilities, which enables both treatment planning and reproducible patient setup, but does not provide good soft tissue contrast or allow monitoring of the target during treatment. We propose a cooperatively-controlled robot to reproducibly position an ultrasound (US) probe on the patient during simulation and treatment, thereby improving soft tissue visualization and allowing real-time monitoring of the target. A key goal of the robotic system is to produce consistent tissue deformations for both CT and US imaging, which simplifies registration of these two modalities. This paper presents the robotic system design and describes a novel control algorithm that employs virtual springs to implement guidance virtual fixtures during "hands on" cooperative control. PMID- 26823989 TI - Inhibition of 12/15-Lipoxygenase Reduces Renal Inflammation and Injury in Streptozotocin-Induced Diabetic Mice. AB - Previous studies suggest that 12/15 lipoxygenase (12/15-LO) is implicated in diabetic vascular complications. We hypothesize that 12/15-LO inhibition attenuates renal inflammation and injury in streptozotocin-induced diabetes. Diabetes was induced in wild-type C57BL/6J (WT) and 12/15-LO deficient mice using streptozotocin. Additionally, four groups of WT mice were also used; control non diabetic, diabetic, diabetic treated with the 12/15-LO inhibitor baicalein for 10 weeks and diabetic treated with baicalein only for the last 4 weeks of the experiment. After 10 weeks of induction of diabetes with streptozotocin, WT diabetic mice exhibited marked elevation in proteinuria together with elevation in the excretion levels of thiobarbituric acid reactive substance (TBARs), a marker of oxidative stress, and monocyte chemoattractant protein-1 (MCP-1), a marker of inflammation and these changes were significantly reduced in 12/15-LO deficient diabetic mice (P<0.05). Similarly, pharmacological inhibition of 12/15 LO with baicalein prevented the elevation in renal 12-HETE production, the major murine metabolic product of 12/15-LO, in diabetic mice, and this effect was associated with decreased proteinuria, TBARs excretion and renal collagen deposition compared to untreated diabetic mice. Interestingly, the protective effects of baicalein were not noticed when only administered in the last 4 weeks of diabetes compared to untreated diabetic mice. WT diabetic mice displayed elevation in renal interleukin-6 (IL-6) levels and these changes were only reduced in diabetic mice treated with baicalein for 10 weeks (P<0.05). The anti inflammatory effects of baicalein or 12/15-LO deficiency were further confirmed in lipopolysaccharide (LPS)-induced acute renal inflammation as inhibition of 12/15-LO reduced the elevation in renal soluble epoxide hydrolase expression in LPS-injected mice. These results suggest that increased 12/15-LO activity and 12 HETE production contribute to the elevation of renal oxidative stress, inflammation and injury in streptozotocin-induced diabetic mice. PMID- 26823990 TI - General Biology and Current Management Approaches of Soft Scale Pests (Hemiptera: Coccidae). AB - We summarize the economic importance, biology, and management of soft scales, focusing on pests of agricultural, horticultural, and silvicultural crops in outdoor production systems and urban landscapes. We also provide summaries on voltinism, crawler emergence timing, and predictive models for crawler emergence to assist in developing soft scale management programs. Phloem-feeding soft scale pests cause direct (e.g., injuries to plant tissues and removal of nutrients) and indirect damage (e.g., reduction in photosynthesis and aesthetic value by honeydew and sooty mold). Variations in life cycle, reproduction, fecundity, and behavior exist among congenerics due to host, environmental, climatic, and geographical variations. Sampling of soft scale pests involves sighting the insects or their damage, and assessing their abundance. Crawlers of most univoltine species emerge in the spring and the summer. Degree-day models and plant phenological indicators help determine the initiation of sampling and treatment against crawlers (the life stage most vulnerable to contact insecticides). The efficacy of cultural management tactics, such as fertilization, pruning, and irrigation, in reducing soft scale abundance is poorly documented. A large number of parasitoids and predators attack soft scale populations in the field; therefore, natural enemy conservation by using selective insecticides is important. Systemic insecticides provide greater flexibility in application method and timing, and have longer residual longevity than contact insecticides. Application timing of contact insecticides that coincides with crawler emergence is most effective in reducing soft scale abundance. PMID- 26823991 TI - A Simple and Rapid LC-MS/MS Method for the Determination of BMCL26 a Novel Anti Parasitic Agent in Rat Plasma. AB - BMCL26 is a potential drug derived from nimesulide, which has exhibited the substantial anti-parasitic activity in various cell lines. To conduct various pharmacological and toxicological properties of this drug, we developed and validated a rapid LC-MS/MS method for its quantification in accordance with the FDA guidelines. Protein precipitation with 0.1% formic acid in acetonitrile was used to extract the analytes along with the internal standard (JCC76) from rat plasma. It was found that the calibration curve of the method had an excellent linearity (r2 >= 0.9993) for the analyte concentration ranging from 0.5 to 100 ng/mL with acceptable inter- and intra-assay, precision, accuracy and stability. The matrix effect and extraction recovery were in the range of 101.30-110.10% and 90.16- 105.00%, respectively. This LC-MS/MS method is simple and rapid and can be used in the future pharmaceutical studies of BMCL26. PMID- 26823992 TI - Minimum Requirements for Taxicab Security Cameras. AB - PROBLEM: The homicide rate of taxicab-industry is 20 times greater than that of all workers. A NIOSH study showed that cities with taxicab-security cameras experienced significant reduction in taxicab driver homicides. METHODS: Minimum technical requirements and a standard test protocol for taxicab-security cameras for effective taxicab-facial identification were determined. The study took more than 10,000 photographs of human-face charts in a simulated-taxicab with various photographic resolutions, dynamic ranges, lens-distortions, and motion-blurs in various light and cab-seat conditions. Thirteen volunteer photograph-evaluators evaluated these face photographs and voted for the minimum technical requirements for taxicab-security cameras. RESULTS: Five worst-case scenario photographic image quality thresholds were suggested: the resolution of XGA-format, highlight dynamic-range of 1 EV, twilight-dynamic-range of 3.3 EV, lens-distortion of 30%, and shutter-speed of 1/30 second. PRACTICAL APPLICATIONS: These minimum requirements will help taxicab regulators and fleets to identify effective taxicab-security cameras, and help taxicab-security camera manufacturers to improve the camera facial identification capability. PMID- 26823993 TI - Identification of AIM2 as a downstream target of JAK2V617F. AB - BACKGROUND: The gain-of-function mutation JAK2V617F is frequently found in Philadelphia-chromosome-negative myeloproliferative neoplasm (MPN) patients. However, the tumorigenic properties of JAK2V617F have mostly been characterized in in vivo and in vitro murine models due to the lack of appropriate human cell lines. METHODS: Using the multipotent hematologic cell line UT-7/GM, we established D9, a novel human cell line that expresses JAK2V617F upon tetracycline addition. We assessed cellular differentiation in UT-7/GM cells when JAK2V617F was induced, and we used microarrays to analyze changes in mRNA expression caused by JAK2V617F. RESULTS: Using the human D9 cell line, we demonstrated that the induction of JAK2V617F leads to cytokine-independent cell growth with increased STAT activation and erythroid differentiation, mimicking the characteristics observed in polycythemia vera, making it a suitable in vitro model for studying this disorder. Interestingly, JAK2V617F-dependent erythroid cell differentiation was blocked when GM-CSF was added to the culture, suggesting that the GM-CSF pathway antagonizes JAK2V617F-induced erythroid cell differentiation. Our microarray analysis identified several genes involved in inflammasome activation, such as AIM2, IL1B, and CASP1, which were significantly up-regulated in JAK2V617F-induced cells. CONCLUSIONS: The observed inflammasome activation following JAK2V617F induction is consistent with a recent report demonstrating the involvement of IL1B in myelofibrosis development in a JAK2V617F model mouse. These results indicate that the D9 cell line should be useful for characterizing the signaling pathways downstream of JAK2V617F, allowing for the identification of effector molecules that contribute to the development of MPN. PMID- 26823994 TI - Anatomical barriers in the right atrium to the coronary sinus cannulation. AB - Background. The coronary venous system is an increasingly frequent target of minimally invasive cardiac procedures. The purpose of this paper is to assess the anatomical barriers in the right atrium to coronary sinus cannulation. Methods. We examined the anatomy of the right atrium, coronary sinus ostium, inferior and superior vena cava ostia in 110 randomly selected autopsied human hearts of both sexes (27% females; mean age 49.2 +/- 17.5 years). Results. The Eustachian valve was present in 79 cases (71.8%) with mean height =4.9 +/- 2.6 mm. The valve was perforated in 11 cases (13.9%). It is typically too small to hinder the coronary sinus catheterization, but in some cases (about 2%) a significantly protruding valve may be an obstacle. Chiari's network (4.6%) is not a barrier to catheter entry into the right atrium but may significantly impede further catheter manipulations inside the heart venous system. A typical Thebesian valve leaves enough space for the passage of the standard catheter to the coronary sinus. Discussion. Detailed anatomy of various anatomical structures within the right atrium that could play a potential role in coronary sinus cannulation is discussed. PMID- 26823995 TI - Not so sluggish: the success of the Felimare picta complex (Gastropoda, Nudibranchia) crossing Atlantic biogeographic barriers. AB - The molecular phylogeny of the Atlanto-Mediterranean species of the genus Felimare, particularly those attributed to the species F. picta, was inferred using two mitochondrial markers (16S and COI). A recent revision of the Chromodorididae clarified the taxonomic relationships at the family level redefining the genus Felimare. However, conflicting taxonomic classifications have been proposed for a restrict group of taxa with overlapping morphological characteristics and geographical distributions designated here as the Felimare picta complex. Three major groups were identified: one Mediterranean and amphi Atlantic group; a western Atlantic group and a tropical eastern Atlantic group. F. picta forms a paraphyletic group since some subspecies are more closely related with taxa traditionaly classified as independent species (e.g. F. zebra) than with other subspecies with allopatric distributions (e.g. F. picta picta and F. picta tema). Usually, nudibranchs have adhesive demersal eggs, short planktonic larval phases and low mobility as adults unless rafting on floating materials occurs. Surprisingly however, the phylogeny of the F. picta complex suggests that they successfully cross main Atlantic biogeographic barriers including the mid-Atlantic barrier. This ability to cross different biogeographic barriers may be related to F. picta's distinct life history and ecological traits. Compared to other Chromodorididae F. picta has larger eggs and planktotrophic larvae which could be related to a longer planktonic phase. PMID- 26823996 TI - Reconstructing ecosystem functions of the active microbial community of the Baltic Sea oxygen depleted sediments. AB - Baltic Sea deep water and sediments hold one of the largest anthropogenically induced hypoxic areas in the world. High nutrient input and low water exchange result in eutrophication and oxygen depletion below the halocline. As a consequence at Landsort Deep, the deepest point of the Baltic Sea, anoxia in the sediments has been a persistent condition over the past decades. Given that microbial communities are drivers of essential ecosystem functions we investigated the microbial community metabolisms and functions of oxygen depleted Landsort Deep sediments by metatranscriptomics. Results show substantial expression of genes involved in protein metabolism demonstrating that the Landsort Deep sediment microbial community is active. Identified expressed gene suites of metabolic pathways with importance for carbon transformation including fermentation, dissimilatory sulphate reduction and methanogenesis were identified. The presence of transcripts for these metabolic processes suggests a potential for heterotrophic-autotrophic community synergism and indicates active mineralisation of the organic matter deposited at the sediment as a consequence of the eutrophication process. Furthermore, cyanobacteria, probably deposited from the water column, are transcriptionally active in the anoxic sediment at this depth. Results also reveal high abundance of transcripts encoding integron integrases. These results provide insight into the activity of the microbial community of the anoxic sediment at the deepest point of the Baltic Sea and its possible role in ecosystem functioning. PMID- 26823998 TI - Systematics of the Rubidgeinae (Therapsida: Gorgonopsia). AB - The subfamily Rubidgeinae, containing the largest known African gorgonopsians, is thoroughly revised. Rubidgeinae is diagnosed by the absence of a blade-like parasphenoid rostrum and reduction or absence of the preparietal. Seven rubidgeine species from the Karoo Basin of South Africa are recognized as valid: Aelurognathus tigriceps, Clelandina rubidgei, Dinogorgon rubidgei, Leontosaurus vanderhorsti, Rubidgea atrox, Smilesaurus ferox, and Sycosaurus laticeps. Rubidgeines are also present in other African basins: A. tigriceps and S. laticeps occur in the Upper Madumabisa Mudstone Formation of Zambia, and D. rubidgei, R. atrox, and the endemic species Ruhuhucerberus haughtoni comb. nov. and Sycosaurus nowaki comb. nov. occur in the Usili Formation of Tanzania. Aelurognathus nyasaensis from the Chiweta Beds of Malawi also represents a rubidgeine, but of uncertain generic referral pending further preparation. No rubidgeine material is known outside of Africa: the purported Russian rubidgeine Leogorgon klimovensis is not clearly referable to this group and may not be diagnosable. Phylogenetic analysis of rubidgeines reveals strong support for a clade (Rubidgeini) of advanced rubidgeines including Clelandina, Dinogorgon, Leontosaurus, and Rubidgea. Support for Smilesaurus as a rubidgeine is weak; it may, as previous authors have suggested, represent an independent evolution of large body size from an Arctops-like ancestor. Temporally, rubidgeines are restricted to the Late Permian, first appearing in the Tropidostoma Assemblage Zone and reaching highest diversity in the Cistecephalus and Daptocephalus assemblage zones of the Beaufort Group. PMID- 26823997 TI - Characterisation of the human uterine microbiome in non-pregnant women through deep sequencing of the V1-2 region of the 16S rRNA gene. AB - Background. It is widely assumed that the uterine cavity in non-pregnant women is physiologically sterile, also as a premise to the long-held view that human infants develop in a sterile uterine environment, though likely reflecting under appraisal of the extent of the human bacterial metacommunity. In an exploratory study, we aimed to investigate the putative presence of a uterine microbiome in a selected series of non-pregnant women through deep sequencing of the V1-2 hypervariable region of the 16S ribosomal RNA (rRNA) gene. Methods. Nineteen women with various reproductive conditions, including subfertility, scheduled for hysteroscopy and not showing uterine anomalies were recruited. Subjects were highly diverse with regard to demographic and medical history and included nulliparous and parous women. Endometrial tissue and mucus harvesting was performed by use of a transcervical device designed to obtain endometrial biopsy, while avoiding cervicovaginal contamination. Bacteria were targeted by use of a barcoded Illumina MiSeq paired-end sequencing method targeting the 16S rRNA gene V1-2 region, yielding an average of 41,194 reads per sample after quality filtering. Taxonomic annotation was pursued by comparison with sequences available through the Ribosomal Database Project and the NCBI database. Results. Out of 183 unique 16S rRNA gene amplicon sequences, 15 phylotypes were present in all samples. In some 90% of the women included, community architecture was fairly similar inasmuch B. xylanisolvens, B. thetaiotaomicron, B. fragilis and an undetermined Pelomonas taxon constituted over one third of the endometrial bacterial community. On the singular phylotype level, six women showed predominance of L. crispatus or L. iners in the presence of the Bacteroides core. Two endometrial communities were highly dissimilar, largely lacking the Bacteroides core, one dominated by L. crispatus and another consisting of a highly diverse community, including Prevotella spp., Atopobium vaginae, and Mobiluncus curtisii. Discussion. Our findings are, albeit not necessarily generalizable, consistent with the presence of a unique microbiota dominated by Bacteroides residing on the endometrium of the human non-pregnant uterus. The transcervical sampling approach may be influenced to an unknown extent by endocervical microbiota, which remain uncharacterised, and therefore warrants further validation. Nonetheless, consistent with our understanding of the human microbiome, the uterine microbiota are likely to have a previously unrecognized role in uterine physiology and human reproduction. Further study is therefore warranted to document community ecology and dynamics of the uterine microbiota, as well as the role of the uterine microbiome in health and disease. PMID- 26823999 TI - The metabolomic profile of gamma-irradiated human hepatoma and muscle cells reveals metabolic changes consistent with the Warburg effect. AB - The two human cell lines HepG2 from hepatoma and HMCL-7304 from striated muscle were gamma-irradiated with doses between 0 and 4 Gy. Abundant gammaH2AX foci were observed at 4 Gy after 4 h of culture post-irradiation. Sham-irradiated cells showed no gammaH2AX foci and therefore no signs of radiation-induced double strand DNA breaks. Flow cytometry indicated that 41.5% of HepG2 cells were in G2/M and this rose statistically significantly with increasing radiation dose reaching a plateau at ~47%. Cell lysates from both cell lines were subjected to metabolomic analysis using Gas Chromatography-Mass Spectrometry (GCMS). A total of 46 metabolites could be identified by GCMS in HepG2 cell lysates and 29 in HMCL-7304 lysates, most of which occurred in HepG2 cells. Principal Components Analysis (PCA) showed a clear separation of sham, 1, 2 and 4 Gy doses. Orthogonal Projection to Latent Structures-Discriminant Analysis (OPLS-DA) revealed elevations in intracellular lactate, alanine, glucose, glucose 6-phosphate, fructose and 5-oxoproline, which were found by univariate statistics to be highly statistically significantly elevated at both 2 and 4 Gy compared with sham irradiated cells. These findings suggested upregulation of cytosolic aerobic glycolysis (the Warburg effect), with potential shunting of glucose through aldose reductase in the polyol pathway, and consumption of reduced Glutathione (GSH) due to gamma-irradiation. In HMCL-7304 myotubes, a putative Warburg effect was also observed only at 2 Gy, albeit a lesser magnitude than in HepG2 cells. It is anticipated that these novel metabolic perturbations following gamma irradiation of cultured cells will lead to a fuller understanding of the mechanisms of tissue damage following ionizing radiation exposure. PMID- 26824000 TI - Combined effect of 17beta-estradiol and resveratrol against apoptosis induced by interleukin-1beta in rat nucleus pulposus cells via PI3K/Akt/caspase-3 pathway. AB - BACKGROUND: In previous studies, both 17beta-estradiol (E2) and resveratrol (RES) were reported to protect intervertebral disc cells against aberrant apoptosis. Given that E2 has a better anti-apoptotic effect with more cancer risk and RES has an anti-apoptotic effect with less cancer risk, the combined use of E2 with RES is promising in developing clinical therapies to treat apoptosis-related diseases such as intervertebral disc degeneration in the future. OBJECTIVE: The purpose of this study was to explore the combined effect of E2 with RES on rat nucleus pulposus cells and the underlying mechanisms. METHODS: TUNEL assay and FACS analysis were used to determine apoptotic incidence of nucleus pulposus cells. MTS assay was used to determine cell viability, and cellular binding assay was used to determine cell-ECM (extracellular matrix) ability. Real-time quantitative RT-PCR was to determine mRNA level of target genes. And Western blot was used to determine the protein level. RESULTS: Both E2 and RES decreased apoptotic incidence when used singly; interestingly, they decreased apoptosis more efficiently when used combinedly. Meanwhile, E2 and RES combined together against the decrease of cell viability and binding ability resulting from IL 1beta cytotoxicity. As well, activated caspase-3 was suppressed by the combined effect. Furthermore, IL-1beta downregulated expression level of type II collagen and aggrecan (standing for anabolism), while upregulated MMP-3 and MMP-13 (standing for catabolism). However, the combined use of E2 with RES effectively abolished the above negative effects caused by IL-1beta, better than either single use. Finally, it turned out to be that E2 and RES combined together against apoptosis via the activation of PI3K/Akt/caspase-3 pathway. CONCLUSION: This study presented that IL-1beta induced aberrant apoptosis, which was efficiently resisted by the combined use of E2 with RES via PI3K/Akt/caspase-3 pathway. PMID- 26824001 TI - Genetic diversity in migratory bats: Results from RADseq data for three tree bat species at an Ohio windfarm. AB - Genetic analyses can identify the scale at which wildlife species are impacted by human activities, and provide demographic information useful for management. Here, we use thousands of nuclear DNA genetic loci to assess whether genetic structure occurs within Lasiurus cinereus (Hoary Bat), L. borealis (Red Bat), and Lasionycteris noctivagans (Silver-Haired Bat) bats found at a wind turbine site in Ohio, and to also estimate demographic parameters in each of these three groups. Our specific goals are to: 1) demonstrate the feasibility of isolating RADseq loci from these tree bat species, 2) test for genetic structure within each species, including any structure that may be associated with time (migration period), and 3) use coalescent-based modeling approaches to estimate genetically effective population sizes and patterns of population size changes over evolutionary timescales. Thousands of loci were successfully genotyped for each species, demonstrating the value of RADseq for generating polymorphic loci for population genetic analyses in these bats. There was no evidence for genetic differentiation between groups of samples collected at different times throughout spring and fall migration, suggesting that individuals from each species found at the wind facility are from single panmictic populations. Estimates of present-day effective population sizes varied across species, but were consistently large, on the order of 10(5)-10(6). All populations show evidence of expansions that date to the Pleistocene. These results, along with recent work also suggesting limited genetic structure in bats across North America, argue that additional biomarker systems such as stable-isotopes or trace elements should be investigated as alternative and/or complementary approaches to genetics for sourcing individuals collected at single wind farm sites. PMID- 26824002 TI - Discrepancy between Measured Serum Total Carbon Dioxide Content and Bicarbonate Concentration Calculated from Arterial Blood Gases. AB - Large differences between the concentrations of serum total carbon dioxide (TCO2) and blood gas bicarbonate (HCO3 (-)) were observed in two consecutive simultaneously drawn sets of samples of serum and arterial blood gases in a patient who presented with severe carbon dioxide retention and profound acidemia. These differences could not be explained by the effect of the high partial pressure of carbon dioxide on TCO2, by variations in the dissociation constant of the carbonic acid/bicarbonate system or by faults caused by the algorithms of the blood gas apparatus that calculate HCO3 (-). A recalculation using the Henderson Hasselbach equation revealed arterial blood gas HCO3 (-) values close to the corresponding serum TCO2 values and clarified the diagnosis of the acid-base disorder, which had been placed in doubt by the large differences between the reported TCO2 and HCO3 (-) values. Human error in the calculation of HCO3 (-) was identified as the source of these differences. Recalculation of blood gas HCO3 ( ) should be the first step in identifying the source of large differences between serum TCO2 and blood gas HCO3 (-). PMID- 26824003 TI - Durable Control and Overall Survival Benefit with Focal Reirradiation in Cervical Cancer. AB - Local recurrence following definitive chemoradiation in cervical cancer ranges from 5-18%. Currently, there are limited options available for patients recurring in para-aortic or iliac lymph nodes. We present two cases of reirradiation for non-central recurrences with intensity-modulated radiotherapy (IMRT). Both patients achieved a complete response with manageable short-term toxicities and no late adverse effects with a follow-up of over one year and three years after reirradiation. While further follow-up is needed, IMRT is a feasible and safe option in cervical cancer patients with recurrent in-field failures involving the lymph nodes. PMID- 26824004 TI - Staged Surgical Management in the Treatment of Primary Epidural Hydatidosis of the Spine: A Case Series and Review. AB - Hydatid disease is a parasitic infection linked to the Echinococcus granulosus tapeworm. Infected cysts can present anywhere in the human body, but the liver is the most frequently involved organ, followed by the lungs. The prognosis is generally poor and may be comparable to that of neoplastic disease. Primary spinal hydatidosis accounts for less than 1% of all cases and virtually all these cases have extradural involvement. We describe a case review consisting of two patients who presented over a three week period with primary spinal extradural hydatidosis in the Western Cape region of South Africa. Both patients presented with lower limb paraparesis and were treated aggressively with two-stage surgical procedures, resulting in a dramatic improvement in their neurological status. PMID- 26824005 TI - Autologous Fat Grafting in Severe Lower Extremity Asymmetries: Report of Four Cases. AB - BACKGROUND: Lower extremity asymmetries are challenging problems in plastic and aesthetic surgery practice. Regardless of their origin, atrophies and asymmetries can be extremely varied and difficult to solve with simple techniques. OBJECTIVES: The author reports his experience in the treatment of four patients suffering from severe lower extremity atrophy and asymmetry of different etiologies with autologous fat grafting. METHODS: A total of four cases are presented. Patient selection was based on the severity of atrophy and asymmetry. Two patients were treated with two sessions of simple fat grafting and two patients with one session of cell-enriched fat grafting. The end point in each session was determined by tension/blanching of soft tissues. All patients were followed up for at least 12 months after the last session. During the postoperative follow-up, variables, such as objective volume improvement, objective girth loss, return to daily activities, and patient satisfaction, were analyzed. RESULTS: The initial analysis of postoperative results showed a good patient satisfaction rate with no relevant complications and an early return to daily activities. Estimated mean volume improvement for simple fat grafting cases was estimated as 44% after two treatments. Mean volume improvement in cell enriched fat grafting cases was estimated as 25% after only one treatment. CONCLUSIONS: Autologous fat grafting is a safe, effective, and reliable technique to perform aesthetic and reconstructive reshaping of a lower extremity in cases of atrophy or severe asymmetry. Depending on the preoperative soft tissue compliance, cell-assisted fat grafting will play an important role in reducing the number of sessions to perform. PMID- 26824006 TI - Response to Anti-PD-1 Therapy in Metastatic Merkel Cell Carcinoma Metastatic to the Heart and Pancreas. AB - Metastatic Merkel cell carcinoma (MCC) is a lethal, Merkel cell polyomavirus (MCPyV) cancer with no currently available effective therapy. Harnessing the immune system through an immune checkpoint blockade is an attractive option because the immune system appears to be dysfunctional in the Merkel cell tumor microenvironment. Although MCPyV is expressed in 80% of MCCs and serves as a powerful antigen for stimulating host immune response, intratumoral CD8+ T-cell infiltration is seen only in 18% of MCCs. In contrast, about 50% of MCPyV positive MCCs express the programmed death-ligand 1 (PD-L1) on multiple cell types in the tumor microenvironment. We present a case of a young patient with MCC involving the heart and pancreas that showed an impressive response after treatment with four cycles of the anti-PD-1 monoclonal antibody, nivolumab. PMID- 26824007 TI - Long-Term Progression-Free Survival in a Patient with Locally Advanced, Unresectable Pancreatic Adenocarcinoma. AB - Pancreatic adenocarcinoma is amongst the most lethal malignancies with dismal five-year survival rates. Surgical excision is the mainstay of therapy and unresectable disease is considered incurable. Herein, we describe a patient with unresectable, advanced stage pancreatic adenocarcinoma with a remarkable clinical course following definitive chemoradiotherapy. PMID- 26824008 TI - Extranodal NK/T-Cell Lymphoma, Nasal Type, Presenting as a Breast Mass. AB - Extranodal natural killer/T-cell lymphoma, nasal type, is a rare type of non Hodgkin cell lymphoma endemic to East Asia and parts of Central and South America. In most cases, it is driven by Epstein-Barr virus infections, with a broad range of morphologic appearances, frequent necrosis, and angioinvasion. It is designated as NK/T reflecting uncertainty in its cellular origins. These tumors usually arise in the nasal region, typically presenting with symptoms of nasal obstruction, epistaxis, and/or a destructive mass involving the nose, sinuses, or palate. The treatment of patients with extranodal NK/T-cell lymphoma, nasal type, is largely determined by the extent of disease. Localized disease is usually treated with radiation and chemotherapy. The disseminated disease requires combination chemotherapy. This report describes the case of a 30-year old Caucasian female presenting with a left breast mass of two months duration. Excisional biopsy was done, and the pathological exam confirmed the diagnosis of extranodal NK/T-cell lymphoma, nasal type. Our patient received a systemic combination chemotherapy with steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) regimen, resulting in a complete clinical and radiological remission. On the basis of our review of the literature, extranodal NK/T non-Hodgkin cell lymphoma, nasal type, presenting as a breast mass is very rare and very uncommon in the United States. Awareness of this occurrence may be valuable as this case may be a forerunner of additional similar cases developing in the future. PMID- 26824009 TI - Oligometastatic Adenocarcinoma of the Lung: A Therapeutic Opportunity for Long Term Survival. AB - We report a case of oligometastatic non-small-cell lung cancer (NSCLC) in a 60 year-old male that was treated with both local and systemic therapies with an exceptional response to therapy. This case provides evidence that oligometastatic lung cancer, when treated with curative intent, may be an opportunity for long term survival in select patients. PMID- 26824010 TI - Intermittent BRAF Inhibition Can Achieve Prolonged Disease Control in BRAF Mutant Melanoma. AB - BRAF V600E is the most common somatic mutation seen in patients with metastatic melanoma. BRAF inhibitors (BRAFi), along with MEK inhibitors (MEKi), have been shown to improve overall survival in these patients with a median time to resistance of 6-10 months. We describe a patient with an ongoing response of 48 months on intermittent BRAFi therapy. She was started on vemurafenib at initial diagnosis, which was discontinued after a total of 39 weeks of therapy, and achieved a complete response due to cumulative toxicity. Upon evidence of progression on serial imaging following 81 weeks of disease-free status, BRAFi was resumed with dabrafenib, along with trametinib. Complete response was seen with seven weeks of treatment. Therapy was discontinued again, due to side effects, with an intention to pursue intermittent therapy. Serial imaging, so far, has shown no progression or recurrence of disease after over a year (66 weeks and ongoing) since discontinuation of therapy. This case underscores the clinical feasibility of intermittent BRAFi therapy in patients while still achieving a prolonged response. Disease control of 48 months, to date, has been achieved using therapy only "as needed" and keeping toxicities to the minimum. PMID- 26824011 TI - Remarkable Response to Methylprednisolone in a Multiple Myeloma Patient with Nodal Disease Refractory to High-Dose Chemotherapy. AB - Multiple myeloma is a disorder of malignant plasma cells, which is characterized by paraprotein production, lytic bone lesions, hypercalcemia, susceptibility to infections, and renal impairment. Here, we describe a patient with IgA myeloma with extensive nodal involvement who obtained significant benefit from high-dose methylprednisolone after failing aggressive induction chemotherapy and high-dose melphalan with autologous stem cell support. PMID- 26824012 TI - Exploring Mechanisms for Effective Technology-Enhanced Simulation-based Education in Wilderness Medicine: A Systematic Review. AB - BACKGROUND: Technology-enhanced simulation is well-established in healthcare teaching curricula, including those regarding wilderness medicine. Compellingly, the evidence base for the value of this educational modality to improve learner competencies and patient outcomes are increasing. AIMS: The aim was to systematically review the characteristics of technology-enhanced simulation presented in the wilderness medicine literature to date. Then, the secondary aim was to explore how this technology has been used and if the use of this technology has been associated with improved learner or patient outcomes. METHODS: EMBASE and MEDLINE were systematically searched from 1946 to 2014, for articles on the provision of technology-enhanced simulation to teach wilderness medicine. Working independently, the team evaluated the information on the criteria of learners, setting, instructional design, content, and outcomes. RESULTS: From a pool of 37 articles, 11 publications were eligible for systematic review. The majority of learners in the included publications were medical students, settings included both indoors and outdoors, and the main focus clinical content was initial trauma management with some including leadership skills. The most prevalent instructional design components were clinical variation and cognitive interactivity, with learner satisfaction as the main outcome. CONCLUSIONS: The results confirm that the current provision of wilderness medicine utilizing technology-enhanced simulation is aligned with instructional design characteristics that have been used to achieve effective learning. Future research should aim to demonstrate the translation of learning into the clinical field to produce improved learner outcomes and create improved patient outcomes. PMID- 26824013 TI - Translational control of the fibroblast-extracellular matrix association: An application to pulmonary fibrosis. AB - Pulmonary fibrosis is a severe lung disease characterized by sustained propagation of lung fibroblasts and relentless accumulation of extracellular matrix (ECM). Idiopathic pulmonary fibrosis (IPF) is the most severe chronic form of pulmonary fibrosis and results both in the gradual exchange of normal lung parenchyma with fibrotic tissue and in the irreversible impairment of gas exchange in the lung. Despite the urgency for novel therapies in IPF treatment, there is no effective and proven medical therapy available. Molecular mechanisms underlying IPF pathogenesis include aberrant ECM signaling through the canonical integrin/PI3K/Akt/mTORC1 signal transduction pathway. One important and well characterized downstream effector of this pathway is the cellular protein synthesis machinery. Here we will review the recent advances in our understanding of the function of ECM and integrin receptor signaling in development of IPF and will present evidence indicating that the dysregulation of the eIF4F-mediated translational apparatus is an important factor in the development and progression of IPF and other fibrotic disorders. We further discuss the perspectives and challenges to curbing this deadly disease by targeting aberrant translation. PMID- 26824014 TI - Eukaryotic initiation factor 4B and the poly(A)-binding protein bind eIF4G competitively. AB - The eukaryotic translation initiation factor (eIF) 4G functions as a scaffold protein that assembles components of the translation initiation complex required to recruit the 40S ribosomal subunit to an mRNA. Although many eukaryotes express two highly similar eIF4G isoforms, those in plants are highly divergent in size and sequence from one another and are referred to as eIF4G and eIFiso4G. Although the domain organization of eIFiso4G differs substantially from eIF4G orthologs in other species, the domain organization of plant eIF4G is largely unknown despite the fact that it is more similar in size and sequence to eIF4G of other eukaryotes. In this study, we show that eIF4G differs from eIFiso4G in that it contains two distinct interaction domains for the poly(A) binding protein (PABP) and eIF4B but is similar to eIFiso4G in having two eIF4A interaction domains. PABP and eIF4B bind the same N-terminal region of eIF4G as they do to a region C proximal to the HEAT-1 domain in the middle domain of eIF4G, resulting in competitive binding between eIF4B and PABP to each site. eIF4G also differs from eIFiso4G in that no competitive binding was observed between PABP and eIF4A or between eIF4B and eIF4A to its HEAT-1-containing region. These results demonstrate that despite substantial differences in size, sequence, and domain organization, PABP and eIF4B bind to eIF4G and eIFiso4G competitively. PMID- 26824015 TI - Fas-activated Ser/Thr phosphoprotein (FAST) is a eukaryotic initiation factor 4E binding protein that regulates mRNA stability and cell survival. AB - The recognition of T cell intracellular antigen-1 (TIA-1) by Fas-activated Ser/Thr phosphoprotein (FAST) results in prolonged cell survival by inducing the expression of inhibitors of apoptosis. Here we show that the functional effects of FAST are dependent on its interactions with eukaryotic translation initiation factor 4E (eIF4E) which is the major cytosolic cap binding protein in cells. FAST binds to eIF4E via a consensus motif ((428)YXXXXLL(433)) that is also found in eIF4G, 4E-BP1/2/3, 4E-T, and cup. A point mutation within this motif at Y(428) dampens the ability of FAST to recognize eIF4E. Wild-type (WT) FAST, but not its Y428G mutant, increases the expression of co-transfected cellular inhibitor of apoptosis-1 (cIAP-1) and beta-gal mRNA and protein, but inhibits the Fas-induced activation of caspase-3. Increased expression of the co-transfected proteins results, in part, from stabilization of mRNA, suggesting that FAST:eIF4E interactions can inhibit mRNA decay. We propose that eIF4E:FAST:TIA-1 complexes regulate the translation and stability of specific mRNAs that encode proteins important for cell survival. PMID- 26824016 TI - Dual use of GTP hydrolysis by elongation factor G on the ribosome. AB - Elongation factor G (EF-G) is a GTPase that catalyzes tRNA and mRNA translocation during the elongation cycle of protein synthesis. The GTP-bound state of the factor on the ribosome has been studied mainly with non-hydrolyzable analogs of GTP, which led to controversial conclusions about the role of GTP hydrolysis in translocation. Here we describe a mutant of EF-G in which the catalytic His91 is replaced with Ala. The mutant EF-G does not hydrolyze GTP, but binds GTP with unchanged affinity, allowing us to study the function of the authentic GTP-bound form of EF-G in translocation. Utilizing fluorescent reporter groups attached to the tRNAs, mRNA, and the ribosome we compile the velocity map of translocation seen from different perspectives. The data suggest that GTP hydrolysis accelerates translocation up to 30-fold and facilitates conformational rearrangements of both 30S subunit (presumably the backward rotation of the 30S head) and EF-G that lead to the dissociation of the factor. Thus, EF-G combines the energy regime characteristic for motor proteins, accelerating movement by a conformational change induced by GTP hydrolysis, with that of a switch GTPase, which upon Pi release switches the conformations of EF-G and the ribosome to low affinity, allowing the dissociation of the factor. PMID- 26824017 TI - IRES-mediated translation of the pro-apoptotic Bcl2 family member PUMA. AB - The proapoptotic Bcl-2 family member PUMA is a critical regulator of apoptosis. We have previously shown that PUMA plays a pivotal role in the apoptosis associated with skeletal myoblast differentiation and that a MyoD-dependent mechanism is responsible for the increased expression of PUMA in these cells. Herein, we report that the increased expression of PUMA under these conditions involves regulation at the level of translation. Specifically, we have found that the increase in PUMA protein levels occurs under conditions of decreased total protein synthesis, eIF2-alpha phosphorylation and hypophosphorylation of eIF4E BP, suggesting that PUMA translation is proceeding via an alternative initiation mechanism. Polyribosome analysis of PUMA mRNA further corroborated this suggestion. A combination of in vitro and ex vivo (cellular) approaches has provided evidence suggesting that PUMA mRNA 5'UTR harbors an Internal Ribosome Entry Site (IRES) element. Using mono- and bi-cistronic reporter constructs, we have delineated an mRNA fragment that allows for cap-independent translation in vitro and ex vivo (in skeletal myoblasts) in response to culture in differentiation media (DM), or in response to treatment with the DNA-damaging agent, etoposide. This mRNA fragment also supports translation in HeLa and 293T cells. Thus, our data has revealed a novel IRES-mediated regulation of PUMA expression in several cell types and in response to several stimuli. These findings contribute to our understanding and potential manipulation of any developmental or therapeutic scenario involving PUMA. PMID- 26824018 TI - Physical evidence supporting a ribosomal shunting mechanism of translation initiation for BACE1 mRNA. AB - In Alzheimer disease, elevated levels of the BACE1 enzyme are correlated with increased production of amyloid peptides and disease pathology. The increase in BACE1 levels is post-transcriptional and may involve altered translation efficiency. Earlier studies have indicated that translation of BACE1 mRNA is cap dependent. As ribosomal subunits move from the cap-structure to the initiation codon, they fail to recognize several AUG codons in the 5' leader. In this study, we looked for physical evidence of the mechanism underlying ribosomal scanning or shunting along the BACE1 5' leader by investigating structural stability in the 5' leaders of endogenous mRNAs in vivo. To perform this analysis, we probed RNAs using lead(II) acetate, a cell-permeable chemical that induces cleavage of unpaired nucleotides having conformational flexibility. The data revealed that the ~440-nt 5' leader was generally resistant to cleavage except for a region upstream of the initiation codon. Cleavage continued into the coding region, consistent with destabilization of secondary structures by translating ribosomes. Evidence that a large segment of the BACE1 5' leader was not cleaved indicates that this region is structurally stable and suggests that it is not scanned. The data support a mechanism of translation initiation in which ribosomal subunits bypass (shunt) part of the BACE1 5' leader to reach the initiation codon. We suggest that a nucleotide bias in the 5' leader may predispose the initiation codon to be more accessible than other AUG codons in the 5' leader, leading to an increase in its relative utilization. PMID- 26824019 TI - Influence of translation factor activities on start site selection in six different mRNAs. AB - Current literature using biochemical assays, structural analyses and genetic manipulations has reported that the key factors associated with the faithful matching of the initiator met-tRNA to the start codon AUG are eIF1, eIF1A and eIF5. However, these findings were in each case based upon the utilization of a single mRNA, perhaps with variations. In an effort to evaluate this general finding, we tested six different mRNAs. Our results confirm that these three proteins are important for start site selection. However, two additional findings would not have been predicted. The first is that eIF1 plays a major role in selecting against start codons that are in close proximity to the 5' end of the mRNA (i.e., less than 21 nucleotides). Second, the addition of eIF5B had nearly the same affect as the addition of eIF5. This is unexpected given the different roles that eIF5 and eIF5B have been proposed to play in the 80S initiation pathway. Finally, although many of the mRNAs appear to respond qualitatively in a similar manner, the quantitative differences noted suggest that there is still some mRNA specific character to our findings. This character may be the length of the 5' UTR, involvement of an IRES element, secondary structure either 5' or 3' of the start codon or specific sequence/structure elements that interact with RNA binding proteins or the ribosome. PMID- 26824021 TI - Introduction to Translation. AB - We introduce here the inaugural issue of the new scientific journal Translation. The overarching aim of this endeavor is to establish a new forum for a broad spectrum of research in the area of protein synthesis in living systems ranging from structural biochemical, evolutionary and regulatory aspects of translation to the fundamental questions related to post-translational control of somatic phenomena in multicellular organisms including human behavior and health. The journal will publish high quality research articles, provide novel insights, ask provocative questions and discuss new hypothesis in this emerging field. Launching a new journal is always challenging. We hope that strong criteria for the peer-review process, transparency of the editorial policy and the scientific reputation of its founders, editors and editorial board assure the success of Translation; and we rely on continuing support of the scientific community in all aspects of the journal's activity. PMID- 26824020 TI - Re-analysis of genome wide data on mammalian microRNA-mediated suppression of gene expression. AB - microRNAs are short endogenously expressed RNAs that regulate gene expression post-transcriptionally. Although both mRNA degradation and suppression of mRNA translation can mediate reduced protein levels following microRNA targeting of an mRNA, their relative contributions have remained elusive. A recent genome-wide study in mammals employing RNA-sequencing to measure microRNA effects on mRNA translation and stability concluded that 84-89% of microRNA-induced suppression of gene expression is due to degradation of target mRNAs. We re-analyzed this data set and applied a number of analysis modifications which revealed that the contribution of mRNA translation was likely underestimated for some mRNA subsets. Moreover, in contrast to the original analysis, our analysis indicated that suppression of mRNA translation precedes mRNA degradation upon microRNA targeting. Our findings thereby enhance our understanding of microRNA mediated genome wide suppression of gene expression in mammals. PMID- 26824022 TI - 4E-BP restrains eIF4E phosphorylation. AB - In eukaryotes, mRNA translation is dependent on the cap-binding protein eIF4E. Through its simultaneous interaction with the mRNA cap structure and with the ribosome-associated eIF4G adaptor protein, eIF4E physically posits the ribosome at the 5' extremity of capped mRNA. eIF4E activity is regulated by phosphorylation on a unique site by the eIF4G-associated kinase MNK. eIF4E assembly with the eIF4G-MNK sub-complex can be however antagonized by the hypophosphorylated forms of eIF4E-binding protein (4E-BP). We show here that eIF4E phosphorylation is dramatically affected by disruption of eIF4E-eIF4G interaction, independently of changes in MNK expression. eIF4E phosphorylation is actually strongly downregulated upon eIF4G shutdown or upon sequestration by hypophosphorylated 4E-BP, consequent to mTOR inhibition. Downregulation of 4E-BP renders eIF4E phosphorylation insensitive to mTOR inhibition. These data highlight the important role of 4E-BP in regulating eIF4E phosphorylation independently of changes in MNK expression. PMID- 26824023 TI - Random mutagenesis of yeast 25S rRNA identify bases critical for 60S subunit structural integrity and function. AB - In yeast Saccharomyces cerevisiae, 25S rRNA makes up the major mass and shape of the 60S ribosomal subunit. During translation initiation, the 60S subunit joins the 40S initiation complex, producing the 80S initiation complex. During elongation, the 60S subunit binds the CCA-ends of aminoacyl- and peptidyl-tRNAs at the A-loop and P-loop, respectively, transferring the peptide onto the alpha amino group of the aminoacyl-tRNA. To study the role of 25S rRNA in translation in vivo, we randomly mutated 25S rRNA and isolated and characterized seven point mutations that affected yeast cell growth and polysome profiles. Four of these mutations, G651A, A1435U, A1446G and A1587G, change a base involved in base triples crucial for structural integrity. Three other mutations change bases near the ribosomal surface: C2879U and U2408C alter the A-loop and P-loop, respectively, and G1735A maps near a Eukarya-specific bridge to the 40S subunit. By polysome profiling in mmslDelta mutants defective in nonfunctional 25S rRNA decay, we show that some of these mutations are defective in both the initiation and elongation phases of translation. Of the mutants characterized, C2879U displays the strongest defect in translation initiation. The ribosome transit time assay directly shows that this mutation is also defective in peptide elongation/termination. Thus, our genetic analysis not only identifies bases critical for structural integrity of the 60S subunit, but also suggests a role for bases near the peptidyl transferase center in translation initiation. PMID- 26824024 TI - Clearance of yeast eRF-3 prion [PSI+] by amyloid enlargement due to the imbalance between chaperone Ssa1 and cochaperone Sgt2. AB - The cytoplasmic [PSI+] element of budding yeast represents the prion conformation of translation release factor eRF-3 (Sup35). Prions are transmissible agents caused by self-seeded highly ordered aggregates (amyloids). Much interest lies in understanding how prions are developed and transmitted. However, the cellular mechanism involved in the prion clearance is unknown. Recently we have reported that excess misfolded multi-transmembrane protein, Dip5DeltaC-v82, eliminates yeast prion [PSI+]. In this study, we showed that the prion loss was caused by enlargement of prion amyloids, unsuitable for transmission, and its efficiency was affected by the cellular balance between the chaperone Hsp70-Ssa1 and Sgt2, a small cochaperone known as a regulator of chaperone targeting to different types of aggregation-prone proteins. The present findings suggest that Sgt2 is titrated by excess Dip5DeltaC-v82, and the shortage of Sgt2 led to non-productive binding of Ssa1 on [PSI+] amyloids. Clearance of prion [PSI+] by the imbalance between Ssa1 and Sgt2 might provide a novel array to regulate the release factor function in yeast. PMID- 26824025 TI - Recent transcriptome-wide mapping of UPF1 binding sites reveals evidence for its recruitment to mRNA before translation. AB - The ATP-dependent RNA helicase UPF1, a key factor in nonsense-mediated mRNA decay (NMD), was so far thought to be recruited specifically to NMD-targeted mRNAs by aberrantly terminating ribosomes. However, two recent publications reporting independently transcriptome-wide mapping of UPF1 occupancy on RNA challenge this model and instead provide evidence that UPF1 binds to mRNA already before translation. According to the new data, UPF1 appears to initially bind all mRNAs along their entire length and gets subsequently stripped off the coding sequence by translating ribosomes. This re-poses the question of where and how UPF1 engages with mRNA and how the NMD-targeted transcripts are selected among the UPF1-bound mRNAs. PMID- 26824026 TI - Cap dependent translation contributes to resistance of myeloma cells to bortezomib. AB - Multiple myeloma (MM) is the second most predominant blood malignancy. Proteasome inhibitors like bortezomib have increased life expectancy, but eventually patients develop resistance to therapy. It was proposed that bortezomib acts through the induction of the Unfolded Protein Response (UPR), i.e., accumulation of misfolded proteins causing a lethal stress response. By this theory, increasing the proteasome load by the stimulation of translation may worsen the UPR. Here we evaluated the crosstalk between translation and bortezomib toxicity in both bortezomib sensitive and resistant cells. We found that bortezomib toxicity does not correlate with induction of proapoptotic eIF2alpha phosphorylation, but rather caused a late reduction in initiation of translation. This effect was accompanied by dephosphorylation of the mTORC1 target 4E-BP1. Infection of myeloma cells with constitutively dephosphorylated 4E-BP1, worsened bortezomib induced cell death. Since mTORC1 inhibitors cause pharmacological inhibition of 4E-BP1 phosphorylation, we tested whether they could act synergistically with bortezomib. We found that both rapamycin, a specific mTORC1 blocker, and PP242 a mTOR antagonist induce the arrest of myeloma cells irrespective of bortezomib sensitivity. Sensitivity to mTOR inhibitors has been associated to the levels of eIF4E/4E-BPs. We found that levels of eIF4E and 4E BPs are variable among patients, and that 15% of myeloma patients have increased levels of 4E-BP1/2. Primary cells of myeloma retain sensitivity to mTOR inhibition, when plated on stromal cells. We propose that translational load does not contribute to bortezomib-induced death, but rather mTOR targeting may be successful in bortezomib resistant patients, stratified for eIF4E/4EBPs. PMID- 26824027 TI - PUNCH-P for global translatome profiling: Methodology, insights and comparison to other techniques. AB - Regulation of mRNA translation is a major modulator of gene expression, allowing cells to fine tune protein levels during growth and differentiation and in response to physiological signals and environmental changes. Mass-spectrometry and RNA-sequencing methods now enable global profiling of the translatome, but these still involve significant analytical and economical limitations. We developed a novel system-wide proteomic approach for direct monitoring of translation, termed PUromycin-associated Nascent CHain Proteomics (PUNCH-P), which is based on the recovery of ribosome-nascent chain complexes from cells or tissues followed by incorporation of biotinylated puromycin into newly synthesized proteins. Biotinylated proteins are then purified by streptavidin and analyzed by mass-spectrometry. Here we present an overview of PUNCH-P, describe other methodologies for global translatome profiling (pSILAC, BONCAT, TRAP/Ribo tag, Ribo-seq) and provide conceptual comparisons between these methods. We also show how PUNCH-P data can be combined with mRNA measurements to determine relative translation efficiency for specific mRNAs. PMID- 26824028 TI - Introducing a class of standardized and interchangeable parts utilizing programmed ribosomal frameshifts for synthetic biology applications. AB - Synthetic biology and the rational design of biological devices depend on the availability of standardized and interchangeable biological parts with diverse range of functions. Reliable access to different reading frames during translation has largely been overlooked as functionality for bioengineering applications. Here we report the construction and initial characterization of the first member of such a class of biological parts that conforms to the BioBrick Standard (RFC25), allowing its interchangeable use in biological devices. Using our standardized frameshifting signal consisting of a UUUAAAG slippery sequence, a 6 nt spacer and an engineered pseudoknot based on the infectious bronchitis virus pseudoknot PK401 embedded in a dual reporter construct, we confirm that the frameshifting activity is comparable to the previously published frequency despite the introduced sequence changes. The frameshifting activity is demonstrated using SDS-PAGE and fluorescence spectroscopy. Standardized programmable ribosomal frameshift parts with specific frameshifting frequencies will be of utility for applications such as double coding DNA sequences by expanding the codable space into the -1 frame. Programmed shifting into the -1 frame to bypass a stop codon allows labeling of a protein pool with a fixed stoichiometry of fusion protein, as well as the construction of multi-enzyme expression constructs with specific expression ratios. A detailed understanding of the structural basis of programmed frameshifting will provide the opportunities to rationally design frameshifting elements with a wide range of applications in synthetic biology, including signals that are regulated by small ligands. PMID- 26824029 TI - Ribosomal protein uS19 mutants reveal its role in coordinating ribosome structure and function. AB - Prior studies identified allosteric information pathways connecting functional centers in the large ribosomal subunit to the decoding center in the small subunit through the B1a and B1b/c intersubunit bridges in yeast. In prokaryotes a single SSU protein, uS13, partners with H38 (the A-site finger) and uL5 to form the B1a and B1b/c bridges respectively. In eukaryotes, the SSU component was split into 2 separate proteins during the course of evolution. One, also known as uS13, participates in B1b/c bridge with uL5 in eukaryotes. The other, called uS19 is the SSU partner in the B1a bridge with H38. Here, polyalanine mutants of uS19 involved in the uS19/uS13 and the uS19/H38 interfaces were used to elucidate the important amino acid residues involved in these intersubunit communication pathways. Two key clusters of amino acids were identified: one located at the junction between uS19 and uS13, and a second that appears to interact with the distal tip of H38. Biochemical analyses reveal that these mutations shift the ribosomal rotational equilibrium toward the unrotated state, increasing ribosomal affinity for tRNAs in the P-site and for ternary complex in the A-site, and inhibit binding of the translocase, eEF2. These defects in turn affect specific aspects of translational fidelity. These findings suggest that uS19 plays a critical role as a conduit of information exchange between the large and small ribosomal subunits directly through the B1a, and indirectly through the B1b/c bridges. PMID- 26824030 TI - Working hard at the nexus between cell signaling and the ribosomal machinery: An insight into the roles of RACK1 in translational regulation. AB - RACK1 is a ribosome-associated protein which functions as a receptor for activated PKCs. It also acts as a scaffold for many other proteins involved in diverse signaling pathways, e.g. Src, JNK, PDE4D and FAK signaling. With such a broad interactome, RACK1 has been suggested to function as a linker between cell signaling and the translation machinery. Accordingly, RACK1 modulates translation at different levels in several model organisms. For instance, it regulates ribosome stalling and mRNA quality control in yeasts and promotes translation efficiency downstream of specific cellular stimuli in mammals. However, the molecular mechanism by which RACK1 exerts these roles is widely uncharacterized. Moreover, the full list of ribosome-recruited RACK1 interactors still needs characterization. Here we discuss in vivo and in vitro findings to better delineate the roles of RACK1 in regulating ribosome function and translation. PMID- 26824031 TI - Novel Glutamatergic Treatments for Severe Mood Disorders. AB - All currently approved antidepressant medications for major depressive disorder (MDD) and bipolar disorder act primarily on the monoaminergic system and have varying affinities for serotonergic, norepinephrine-ergic, and/or dopaminergic receptors. Unfortunately, these drugs are only effective in approximately two thirds of patients. Glutamate is the major excitatory neurotransmitter in the central nervous system, and the glutamatergic system has been implicated in the pathophysiology of MDD. Here, we review the putative involvement of the glutamate receptor subtypes-N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxyl-5-methyl-4 isoxazoleproprionic acid (AMPA), kainate, and the group I, II, and III metabotropic glutamate receptors (mGluRs)-in the development of novel and more effective treatments for MDD as well as preclinical and clinical trials of drugs targeting these receptors. The rapid and robust antidepressant effects of ketamine-an NMDA receptor antagonist-have been consistently replicated in multiple trials. Other glutamatergic drugs have been investigated with varying success. Here, we highlight some of the most interesting results, including: 1) repeated oral, intramuscular, and sublingual ketamine appears to be less robustly effective than intravenous ketamine, but also causes fewer significant adverse effects; 2) the glycine partial agonist GLYX-13 appears to be effective both as monotherapy and adjunctive treatment in the treatment of MDD. An oral analogue, NRX-1074, is currently under investigation; and 3) mGluR modulators targeting mGluR5 have demonstrated convincing preclinical results. PMID- 26824032 TI - Evaluation and Treatment of Childhood Enthesitis-Related Arthritis. PMID- 26824033 TI - Quantification and Gene Expression Analysis of Histone Deacetylases in Common Bean during Rust Fungal Inoculation. AB - Histone deacetylases (HDACs) play an important role in plant growth, development, and defense processes and are one of the primary causes of epigenetic modifications in a genome. There was only one study reported on epigenetic modifications of the important legume crop, common bean, and its interaction with the fungal rust pathogen Uromyces appendiculatus prior to this project. We measured the total active HDACs levels in leaf tissues and observed expression patterns for the selected HDAC genes at 0, 12, and 84 hours after inoculation in mock inoculated and inoculated plants. Colorimetric analysis showed that the total amount of HDACs present in the leaf tissue decreased at 12 hours in inoculated plants compared to mock inoculated control plants. Gene expression analyses indicated that the expression pattern of gene PvSRT1 is similar to the trend of total active HDACs in this time course experiment. Gene PvHDA6 showed increased expression in the inoculated plants during the time points measured. This is one of the first attempts to study expression levels of HDACs in economically important legumes in the context of plant pathogen interactions. Findings from our study will be helpful to understand trends of total active HDACs and expression patterns of these genes under study during biotic stress. PMID- 26824034 TI - Validation of Urine Test for Detection of Helicobacter pylori Infection in Indonesian Population. AB - We measured the accuracy of the urine test (RAPIRUN) for detection of Helicobacter pylori infection in Indonesia (Jakarta, Pontianak, and Jayapura) using histology confirmed by immunohistochemistry and/or culture as gold standards. We also used immunohistochemistry to identify CagA phenotype and analyzed H. pylori CagA diversity in Indonesia. The overall prevalence of H. pylori infection in 88 consecutive dyspeptic patients based on the urine test was 15.9% (14/88), 38.1% for patients in Jayapura that had higher prevalence of H. pylori infection than that in Jakarta (9.7%, P = 0.02) and Pontianak (8.3%, P = 0.006). Overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of RAPIRUN were 83.3%, 94.7%, 71.4%, 97.3%, and 93.2%, respectively. All of the H. pylori-positive patients were immunoreactive for anti-CagA antibody but not immunoreactive for East Asian specific anti-CagA antibody in all H. pylori-positive subjects. We confirmed the high accuracy of RAPIRUN in Indonesian population. In general, we found less virulent type of H. pylori in Indonesia, which partly explained the low incidence gastric cancer in Indonesia. PMID- 26824035 TI - The Need for Biomarkers in Diagnosis and Prognosis of Drug-Induced Liver Disease: Does Metabolomics Have Any Role? AB - Drug-induced liver injury (DILI) is a potentially fatal adverse event and the leading cause of acute liver failure in the US and in the majority of Europe. The liver can be affected directly, in a dose-dependent manner, or idiosyncratically, independently of the dose, and therefore unpredictably. Currently, DILI is a diagnosis of exclusion that physicians should suspect in patients with unexplained elevated liver enzymes. Therefore, new diagnostic and prognostic biomarkers are necessary to achieve an early and reliable diagnosis of DILI and thus improve the prognosis. Although several DILI biomarkers have been found through analytical and genetic tests and pharmacokinetic approaches, none of them have been able to display enough specificity and sensitivity, so new approaches are needed. In this sense, metabolomics is a strongly and promising emerging field that, from biofluids collected through minimally invasive procedures, can obtain early biomarkers of toxicity, which may constitute specific indicators of liver damage. PMID- 26824036 TI - Potentially Functional Polymorphisms in POU5F1 Gene Are Associated with the Risk of Lung Cancer in Han Chinese. AB - POU5F1 is a key regulator of self-renewal and differentiation in embryonic stem cells and may be associated with initiation, promotion, and progression in cancer. We hypothesized that functional polymorphisms in POU5F1 may play an important role in modifying the lung cancer risk. To test this hypothesis, we conducted a case-control study to explore the association between 17 potentially functional SNPs in POU5F1 gene and the lung cancer risk in 1,341 incident lung cancer cases and 1,982 healthy controls in a Chinese population. We found that variant alleles of rs887468 and rs3130457 were significantly associated with increased risk of lung cancer after multiple comparison (OR = 1.29, 95% CI: 1.11 1.51, P fdr = 0.017 for rs887468; OR = 1.29, 95% CI: 1.10-1.51, P fdr = 0.034 for rs3130457, resp.). In addition, we detected a significant interaction between rs887468 genotypes and smoking status on lung cancer risk (P = 0.017). Combined analysis of these 2 SNPs showed a significant allele-dosage association between the number of risk alleles and increased risk of lung cancer (P trend < 0.001). These findings indicate that potentially functional polymorphisms in POU5F1 gene may contribute to lung cancer susceptibility in a Chinese population. PMID- 26824037 TI - Comparative Study of the Antioxidant Effects of Metformin, Glibenclamide, and Repaglinide in Alloxan-Induced Diabetic Rats. AB - Diabetes mellitus is one of the serious global health problems affecting a significant proportion of both developed and developing countries. Overproduction of free radicals and oxidative stress has been associated with the development of diabetic complications. In the present study, the antioxidant effects of metformin (MET), glibenclamide (GLI), and repaglinide (REP) were evaluated in alloxan-induced diabetic rats. The findings from this study may possibly help in understanding the efficacy of these standard drugs in managing the complications arising from diabetes mellitus (DM). Alloxan (130 mg/kg BW) was administered as a single dose to induce diabetes. Four (4) groups of rats (n = 6) were used; group 1 served as diabetic control while groups 2, 3, and 4 were the diabetic test groups that received MET (25 mg/kg), GLI (2.5 mg/kg), and REP (0.5 mg/kg), respectively. The result of the study showed significant (p < 0.05) improvement in the altered antioxidant enzymes (SOD, CAT) and GSH concentration in diabetic treated rats compared with the diabetic control group. MET and REP produced significant effect on the MDA concentration while GLI showed insignificant reduction in the MDA concentration compared with the diabetic control. Findings from this study suggest that the administration of MET, GLI, and REP exerts significant antioxidant effects in alloxan-induced diabetic rats, thus contributing to the protective effect against oxidative stress-induced damage during diabetic complications. PMID- 26824038 TI - Immune Cells and Inflammation in Diabetic Nephropathy. AB - Diabetic nephropathy (DN) is a serious complication of diabetes. At its core, DN is a metabolic disorder which can also manifest itself in terms of local inflammation in the kidneys. Such inflammation can then drive the classical markers of fibrosis and structural remodeling. As a result, resolution of immune mediated inflammation is critical towards achieving a cure for DN. Many immune cells play a part in DN, including key members of both the innate and adaptive immune systems. While these cells were classically understood to primarily function against pathogen insult, it has also become increasingly clear that they also serve a major role as internal sensors of damage. In fact, damage sensing may serve as the impetus for much of the inflammation that occurs in DN, in a vicious positive feedback cycle. Although direct targeting of these proinflammatory cells may be difficult, new approaches that focus on their metabolic profiles may be able to alleviate DN significantly, especially since dysregulation of the local metabolic environment may well be responsible for triggering inflammation to begin with. In this review, the authors consider the metabolic profile of several relevant immune types and discuss their respective roles. PMID- 26824039 TI - The Microtubule-Associated Protein Tau and Its Relevance for Pancreatic Beta Cells. AB - Structural and biochemical alterations of the microtubule-associated protein tau (MAPT) are associated with degenerative disorders referred to as tauopathies. We have previously shown that MAPT is present in human islets of Langerhans, human insulinomas, and pancreatic beta-cell line models, with biophysical similarities to the pathological MAPT in the brain. Here, we further studied MAPT in pancreatic endocrine tissue to better understand the mechanisms that lead to functional dysregulation of pancreatic beta cells. We found upregulation of MAPT protein expression in human insulinomas when compared to human pancreatic islets of Langerhans and an imbalance between MAPT isoforms in insulinomas tissue. We cloned one 3-repeat domain MAPT and transduced this into a beta-cell derived rodent cell line Rin-5F. Proliferation experiments showed higher growth rates and metabolic activities of cells overexpressing MAPT protein. We observed that a MAPT overexpressing cell line demonstrates altered insulin transcription, translation, and insulin secretion rates. We found the relative insulin secretion rates were significantly decreased in a MAPT overexpressing cell line and these findings could be confirmed using partial MAPT knock-down cell lines. Our findings support that MAPT may play an important role in insulin granule trafficking and indicate the importance of balanced MAPT phosphorylation and dephosphorylation for adequate insulin release. PMID- 26824040 TI - Impact of Pancreatic Rat Islet Density on Cell Survival during Hypoxia. AB - In bioartificial pancreases (BP), the number of islets needed to restore normoglycaemia in the diabetic patient is critical. However, the confinement of a high quantity of islets in a limited space may impact islet survival, particularly in regard to the low oxygen partial pressure (PO2) in such environments. The aim of the present study was to evaluate the impact of islet number in a confined space under hypoxia on cell survival. Rat islets were seeded at three different concentrations (150, 300, and 600 Islet Equivalents (IEQ)/cm(2)) and cultured in normal atmospheric pressure (160 mmHg) as well as hypoxic conditions (15 mmHg) for 24 hours. Cell viability, function, hypoxia induced changes in gene expression, and cytokine secretion were then assessed. Notably, hypoxia appeared to induce a decrease in viability and increasing islet density exacerbated the observed increase in cellular apoptosis as well as the loss of function. These changes were also associated with an increase in inflammatory gene transcription. Taken together, these data indicate that when a high number of islets are confined to a small space under hypoxia, cell viability and function are significantly impacted. Thus, in order to improve islet survival in this environment during transplantation, oxygenation is of critical importance. PMID- 26824041 TI - Acute Hypoglycemia Induces Painful Neuropathy and the Treatment of Coenzyme Q10. AB - Diabetic neuropathic pain is reduced with tight glycemic control. However, strict control increases the risk of hypoglycemic episodes, which are themselves linked to painful neuropathy. This study explored the effects of hypoglycemia-related painful neuropathy. Pretreatment with coenzyme Q10 (CoQ10) was performed to explore the preventive effect of CoQ10 on hypoglycemia-related acute neuropathic pain. Two strains of mice were used and 1 unit/kg of insulin was given to induce hypoglycemia. Mechanical sensitivity of hindpaw withdrawal thresholds was measured using von Frey filaments. Blood glucose levels were clamped at normal levels by joint insulin and glucose injection to test whether insulin itself induced hypersensitivity. Results suggest that the increased mechanical sensitivity after insulin injection is related to decreased blood glucose levels. When blood glucose levels remained at a normal level by the linked administration of insulin and glucose, mice demonstrated no significant change in mechanical sensitivity. Pretreatment with CoQ10 prevented neuropathic pain and the expression of the stress factor c-Fos. These results support the concept that pain in the diabetic scenario can be the result of hypoglycemia and not insulin itself. Additionally, pretreatment with CoQ10 may be a potent preventive method for the development of neuropathic pain. PMID- 26824042 TI - Myocardial Perfusion and Function Are Distinctly Altered by Sevoflurane Anesthesia in Diet-Induced Prediabetic Rats. AB - Preservation of myocardial perfusion during surgery is particularly important in patients with increased risk for perioperative complications, such as diabetes. Volatile anesthetics, like sevoflurane, have cardiodepressive effects and may aggravate cardiovascular complications. We investigated the effect of sevoflurane on myocardial perfusion and function in prediabetic rats. Rats were fed a western diet (WD; n = 18) or control diet (CD; n = 18) for 8 weeks and underwent (contrast) echocardiography to determine perfusion and function during baseline and sevoflurane exposure. Myocardial perfusion was estimated based on the product of microvascular filling velocity and blood volume. WD-feeding resulted in a prediabetic phenotype characterized by obesity, hyperinsulinemia, hyperlipidemia, glucose intolerance, and hyperglycemia. At baseline, WD-feeding impaired myocardial perfusion and systolic function compared to CD-feeding. Exposure of healthy rats to sevoflurane increased the microvascular filling velocity without altering myocardial perfusion but impaired systolic function. In prediabetic rats, sevoflurane did also not affect myocardial perfusion; however, it further impaired systolic function. Diet-induced prediabetes is associated with impaired myocardial perfusion and function in rats. While sevoflurane further impaired systolic function, it did not affect myocardial perfusion in prediabetic rats. Our findings suggest that sevoflurane anesthesia leads to uncoupling of myocardial perfusion and function, irrespective of the metabolic state. PMID- 26824043 TI - A Comparison of hs-CRP Levels in New Diabetes Groups Diagnosed Based on FPG, 2 hPG, or HbA1c Criteria. AB - Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) have been used to diagnose new-onset diabetes mellitus (DM) in order to simplify the diagnostic tests compared with the 2-hour oral glucose tolerance test (OGTT; 2-hPG). We aimed to identify optimal cut-off points of high sensitive C-reactive protein (hs CRP) in new-onset DM people based on FPG, 2-hPG, or HbA1c methods. Data derived from recent population-based survey in Turkey (TURDEP-II). The study included 26,499 adult people (63% women, response rate 85%). The mean serum concentration of hs-CRP in women was higher than in men (p < 0.001). The people with new-onset DM based on HbA1c had higher mean hs-CRP level than FPG based and 2-hPG based DM cases. In HbA1c, 2-hPG, and FPG based new-onset DM people, cut-off levels of hs CRP in women were 2.9, 2.1, and 2.5 mg/L [27.5, 19.7, and 23.5 nmol/L] and corresponding values in men were 2.0, 1.8, and 1.8 mg/L (19.0, 16.9, and 16.9 nmol/L), respectively (sensitivity 60-65% and specificity 54-64%). Our results revealed that hs-CRP may not further strengthen the diagnosis of new-onset DM. Nevertheless, the highest hs-CRP level observed in new-onset DM people diagnosed with HbA1c criterion supports the general assumption that this method might recognize people in more advanced diabetic stage compared with other diagnostic methods. PMID- 26824044 TI - Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet Antibodies. AB - As numerous studies put in evidence the increasing incidence of type 1 diabetes (T1D) in children, an early diagnosis is of great importance to define correct treatment and diet. Currently, the identification of classical islet autoantibodies is the primary biomarker for diagnosis in subjects at risk, especially in pediatric patients. Recent studies suggest that detection of antibodies against ZnT8 protein in preclinical phase can predict the development of T1D. We previously demonstrated a significant association of Mycobacterium avium subspecies paratuberculosis (MAP) with T1D in adult Sardinian patients. To enforce this finding, we investigated the presence of antibodies against ZnT8 and proinsulin (PI) with respective homologous epitopes: MAP3865c133-141/ZnT8186-194, MAP3865c125-133/ZnT8178-186, MAP2404c70-85/PI46-61, and MAP1,4alphagbp157 173/PI64-80, in 23 children at risk for T1D, formerly involved in the TRIGR study, and 22 healthy controls (HCs). Positivity to anti-MAP and homologous human peptides was detected in 48% of at-risk subjects compared to 5,85% HCs, preceding appearance of islet autoantibodies. Being MAP easily transmitted to humans with infected cow's milk and detected in retail infant formulas, MAP epitopes could be present in extensively hydrolyzed formula and act as antigens stimulating beta cell autoimmunity. PMID- 26824045 TI - Awaking Blood Pressure Surge and Progression to Microalbuminuria in Type 2 Normotensive Diabetic Patients. AB - BACKGROUND: We investigated the predictive value of morning blood pressure surge (MBPS) on the development of microalbuminuria in normotensive adults with a recent diagnosis of type 2 diabetes. METHODS: Prospective assessments of 24-hour ambulatory blood pressure monitoring and urinary albumin excretion were performed in 377 adult patients. Multivariate-adjusted Cox regression models were used to assess hazard ratios (HRs) between baseline and changes over follow-up in MBPS and the risk of microalbuminuria. The MBPS was calculated as follows: mean systolic BP during the 2 hours after awakening minus mean systolic BP during the 1 hour that included the lowest sleep BP. RESULTS: After a mean follow-up of 6.5 years, microalbuminuria developed in 102 patients. An increase in MBPB during follow-up was associated with an increased risk of microalbuminuria. Compared to individuals in the lowest tertile (-0.67 +/- 1.10 mmHg), the HR and 95% CI for microalbuminuria in those in the highest tertile of change (24.86 +/- 6.92 mmHg) during follow-up were 17.41 (95% CI 6.26-48.42); p for trend <0.001. Mean SD MBPS significantly increased in those who developed microalbuminuria from a mean [SD] of 10.6 [1.4] to 36.8 [7.1], p < 0.001. CONCLUSION: An increase in MBPS is associated with the risk of microalbuminuria in normotensive adult patients with type 2 diabetes. PMID- 26824046 TI - Resting Heart Rate Does Not Predict Cardiovascular and Renal Outcomes in Type 2 Diabetic Patients. AB - Elevated resting heart rate (RHR) has been associated with increased risk of mortality and cardiovascular events. Limited data are available so far in type 2 diabetic (T2DM) subjects with no study focusing on progressive renal decline specifically. Aims of our study were to verify RHR as a simple and reliable predictor of adverse disease outcomes in T2DM patients. A total of 421 T2DM patients with variable baseline stage of diabetic kidney disease (DKD) were prospectively followed. A history of the cardiovascular disease was present in 81 (19.2%) patients at baseline, and DKD (glomerular filtration rate < 60 mL/min or proteinuria) was present in 328 (77.9%) at baseline. Progressive renal decline was defined as a continuous rate of glomerular filtration rate loss >= 3.3% per year. Resting heart rate was not significantly higher in subjects with cardiovascular disease or DKD at baseline compared to those without. Using time to-event analyses, significant differences in the cumulative incidence of the studied outcomes, that is, progression of DKD (and specifically progressive renal decline), major advanced cardiovascular event, and all-cause mortality, between RHR =65 (arbitrary cut-off) and 75 (median) bpm were not found. We did not ascertain predictive value of the RHR for the renal or cardiovascular outcomes in T2DM subjects in Czech Republic. PMID- 26824047 TI - Type 2 Diabetes and ADP Receptor Blocker Therapy. AB - Type 2 diabetes (T2D) is associated with several abnormalities in haemostasis predisposing to thrombosis. Moreover, T2D was recently connected with a failure in antiplatelet response to clopidogrel, the most commonly used ADP receptor blocker in clinical practice. Clopidogrel high on-treatment platelet reactivity (HTPR) was repeatedly associated with the risk of ischemic adverse events. Patients with T2D show significantly higher residual platelet reactivity on ADP receptor blocker therapy and are more frequently represented in the group of patients with HTPR. This paper reviews the current knowledge about possible interactions between T2D and ADP receptor blocker therapy. PMID- 26824048 TI - Implication of Cytotoxic Helicobacter pylori Infection in Autoimmune Diabetes. AB - Background. Type 1 diabetes (T1D) and type 2 diabetes (T2D) have been linked to Helicobacter pylori infection, although results are conflicting. No previous study addressed a possible link between H. pylori infection and latent autoimmune diabetes in adults (LADA). In this study, a correlation among H. pylori infection and the risk of autoimmune diabetes in comparison with T2D was investigated. Methods. Sera from 234 LADA patients, 105 patients with late-onset T1D, and 156 patients with T2D were analyzed for anti-H. pylori and the cytotoxin-associated antigen (CagA) IgG antibodies. Results. H. pylori seroprevalence was comparable in LADA (52%), late-onset T1D (45%), and T2D (49%) with no gender differences. The seroprevalence of CagA IgG was significantly higher in autoimmune diabetes (late-onset T1D: 45%, LADA: 40%) compared to T2D (25%; p < 0.028). Conclusions. Although H. pylori seroprevalence was similar in LADA, T1D, and T2D, anti-CagA positivity was significantly increased among patients with autoimmune diabetes, suggesting that more virulent H. pylori strains might be a trigger for immune mechanisms involved in their pathogenesis. PMID- 26824051 TI - Corrigendum to "GK-1 Improves the Immune Response Induced by Bone Marrow Dendritic Cells Loaded with MAGE-AX in Mice with Melanoma". PMID- 26824049 TI - An HLA-Transgenic Mouse Model of Type 1 Diabetes That Incorporates the Reduced but Not Abolished Thymic Insulin Expression Seen in Patients. AB - Type 1 diabetes (T1D) is an autoimmune disease characterized by T cell-mediated destruction of the pancreatic islet beta cells. Multiple genetic loci contribute to disease susceptibility in humans, with the most responsible locus being the major histocompatibility complex (MHC). Certain MHC alleles are predisposing, including the common HLA-A(*)02:01. After the MHC, the locus conferring the strongest susceptibility to T1D is the regulatory region of the insulin gene, and alleles associated with reduced thymic insulin expression are predisposing. Mice express two insulin genes, Ins1 and Ins2. While both are expressed in beta cells, only Ins2 is expressed in the thymus. We have developed an HLA-A(*)02:01 transgenic NOD-based T1D model that is heterozygous for a functional Ins2 gene. These mice exhibit reduced thymic insulin expression and accelerated disease in both genders. Immune cell populations are not grossly altered, and the mice exhibit typical signs of islet autoimmunity, including CD8 T cell responses to beta cell peptides also targeted in HLA-A(*)02:01-positive type 1 diabetes patients. This model should find utility as a tool to uncover the mechanisms underlying the association between reduced thymic insulin expression and T1D in humans and aid in preclinical studies to evaluate insulin-targeted immunotherapies for the disease. PMID- 26824050 TI - Clopidogrel Protects Endothelium by Hindering TNFalpha-Induced VCAM-1 Expression through CaMKKbeta/AMPK/Nrf2 Pathway. AB - Clopidogrel (INN), an oral antiplatelet drug, has been revealed to have a number of biological properties, for instance, anti-inflammation and antioxidation. Oxidative stress plays an imperative role in inflammation, diabetes mellitus, atherosclerosis, and cancer. In the present study, human aortic endothelial cells (HAECs) were employed to explore the anti-inflammatory activity of INN. INN reduced TNFalpha-induced reactive oxygen species (ROS) generation and time dependently prompted the expression and activity of heme oxygenase 1 (HO-1). Cellular glutathione (GSH) levels were augmented by INN. shHO-1 blocked the INN suppression of TNFalpha-induced HL-60 cell adhesion. The CaMKKbeta/AMPK pathway and Nrf2 transcriptional factor were implicated in the induction of HO-1 by INN. Additionally, TNFalpha dramatically augmented VCAM-1 expression at protein and mRNA levels. INN treatment strikingly repressed TNFalpha-induced expression of VCAM-1 and HL-60 cell adhesion. Compound C, an AMPK inhibitor, and shNrf2 abolished TNFalpha-induced expression of VCAM-1 and HL-60 cell adhesion. Our data suggest that INN diminishes TNFalpha-stimulated VCAM-1 expression at least in part via HO-1 induction, which is CaMKKbeta/AMPK pathway-dependent. PMID- 26824053 TI - Quality and Quantity of Rehabilitation Exercises Delivered By A 3-D Motion Controlled Camera: A Pilot Study. AB - INTRODUCTION: Tele-rehabiliation technologies that track human motion could enable physical therapy in the home. To be effective, these systems need to collect critical metrics without PT supervision both in real time and in a store and forward capacity. The first step of this process is to determine if PTs (PTs) are able to accurately assess the quality and quantity of an exercise repetition captured by a tele-rehabilitation platform. The purpose of this pilot project was to determine the level of agreement of quality and quantity of an exercise delivered and assessed by the Virtual Exercise Rehabilitation Assistant (VERA), and seven PTs. METHODS: Ten healthy subjects were instructed by a PT in how to perform four lower extremity exercises. Subjects then performed each exercises delivered by VERA which counted repetitions and quality. Seven PTs independently reviewed video of each subject's session and assessed repetitions quality. The percent difference in total repetitions and analysis of the distribution of rating repetition quality was assessed between the VERA and PTs. RESULTS: The VERA counted 426 repetitions across 10 subjects performing the four different exercises while the mean repetition count from the PT panel was 426.7 (SD = 0.8). The VERA underestimated the total repetitions performed by 0.16% (SD = 0.03%, 95% CI 0.12 - 0. 22). Chi square analysis across raters was chi2 = 63.17 (df = 6, p<.001), suggesting significant variance in at least one rater. CONCLUSION: The VERA count of repetitions was accurate in comparison to a seven member panel of PTs. For exercise quality the VERA was able to rate 426 exercise repetitions across 10 patients and four different exercises in a manner consistent with five out of seven experienced PTs. PMID- 26824052 TI - Electroporated Antigen-Encoding mRNA Is Not a Danger Signal to Human Mature Monocyte-Derived Dendritic Cells. AB - For therapeutic cancer vaccination, the adoptive transfer of mRNA-electroporated dendritic cells (DCs) is frequently performed, usually with monocyte-derived, cytokine-matured DCs (moDCs). However, DCs are rich in danger-sensing receptors which could recognize the exogenously delivered mRNA and induce DC activation, hence influencing the DCs' immunogenicity. Therefore, we examined whether electroporation of mRNA with a proper cap and a poly-A tail of at least 64 adenosines had any influence on cocktail-matured moDCs. We used 16 different RNAs, encoding tumor antigens (MelanA, NRAS, BRAF, GNAQ, GNA11, and WT1), and variants thereof. None of those RNAs induced changes in the expression of CD25, CD40, CD83, CD86, and CD70 or the secretion of the cytokines IL-8, IL-6, and TNFalpha of more than 1.5-fold compared to the control condition, while an mRNA encoding an NF-kappaB-activation protein as positive control induced massive secretion of the cytokines. To determine whether mRNA electroporation had any effect on the whole transcriptome of the DCs, we performed microarray analyses of DCs of 6 different donors. None of 60,000 probes was significantly different between mock-electroporated DCs and MelanA-transfected DCs. Hence, we conclude that no transcriptional programs were induced within cocktail-matured DCs by electroporation of single tumor-antigen-encoding mRNAs. PMID- 26824054 TI - Age and Sex Specific Reference Intervals for Modifiable Risk Factors of Cardiovascular Diseases for Gujarati Asian Indians. AB - Objective. We aimed to establish age and sex specific percentile reference data for cardiovascular risk factors such as lipids, sugar, blood pressure, and BMI in apparently healthy and disease-free Gujarati population. Methods. In this cross sectional study, we enrolled 3265 apparently healthy and disease-free individuals of both genders residing in Gujarat state. Fasting samples of blood were used for biochemical estimations of lipids and sugar. The measurement of BMI and blood pressure was also done according to the standard guidelines. Age and gender specific 5th, 25th, 50th, 75th, 90th, and 95th percentiles were obtained. Results. The mean values of lipids, sugar, blood pressure, and BMI were significantly (p < 0.001) higher in males as compared to female population. Age wise distribution trends showed increase in the risk factors from the 2nd decade until the 5th to 6th decade in most of the cases, where loss of premenopausal protection in females was also observed. Specific trends according to gender and age were observed in percentile values of various parameters. Conclusion. The outcome of current study will contribute significantly to proposing clinically important reference values of various lipids, sugar, blood pressure, and BMI that could be used to screen the asymptomatic Gujarati Indian population with a propensity of developing dyslipidemia, diabetes, blood pressure, and obesity. PMID- 26824055 TI - A single-ligand ultra-microporous MOF for precombustion CO2 capture and hydrogen purification. AB - Metal organic frameworks (MOFs) built from a single small ligand typically have high stability, are rigid, and have syntheses that are often simple and easily scalable. However, they are normally ultra-microporous and do not have large surface areas amenable to gas separation applications. We report an ultra microporous (3.5 and 4.8 A pores) Ni-(4-pyridylcarboxylate)2 with a cubic framework that exhibits exceptionally high CO2/H2 selectivities (285 for 20:80 and 230 for 40:60 mixtures at 10 bar, 40 degrees C) and working capacities (3.95 mmol/g), making it suitable for hydrogen purification under typical precombustion CO2 capture conditions (1- to 10-bar pressure swing). It exhibits facile CO2 adsorption-desorption cycling and has CO2 self-diffusivities of ~3 * 10(-9) m(2)/s, which is two orders higher than that of zeolite 13X and comparable to other top-performing MOFs for this application. Simulations reveal a high density of binding sites that allow for favorable CO2-CO2 interactions and large cooperative binding energies. Ultra-micropores generated by a small ligand ensures hydrolytic, hydrostatic stabilities, shelf life, and stability toward humid gas streams. PMID- 26824056 TI - Enzymatically active biomimetic micropropellers for the penetration of mucin gels. AB - In the body, mucus provides an important defense mechanism by limiting the penetration of pathogens. It is therefore also a major obstacle for the efficient delivery of particle-based drug carriers. The acidic stomach lining in particular is difficult to overcome because mucin glycoproteins form viscoelastic gels under acidic conditions. The bacterium Helicobacter pylori has developed a strategy to overcome the mucus barrier by producing the enzyme urease, which locally raises the pH and consequently liquefies the mucus. This allows the bacteria to swim through mucus and to reach the epithelial surface. We present an artificial system of reactive magnetic micropropellers that mimic this strategy to move through gastric mucin gels by making use of surface-immobilized urease. The results demonstrate the validity of this biomimetic approach to penetrate biological gels, and show that externally propelled microstructures can actively and reversibly manipulate the physical state of their surroundings, suggesting that such particles could potentially penetrate native mucus. PMID- 26824058 TI - Reconciling past changes in Earth's rotation with 20th century global sea-level rise: Resolving Munk's enigma. AB - In 2002, Munk defined an important enigma of 20th century global mean sea-level (GMSL) rise that has yet to be resolved. First, he listed three canonical observations related to Earth's rotation [(i) the slowing of Earth's rotation rate over the last three millennia inferred from ancient eclipse observations, and changes in the (ii) amplitude and (iii) orientation of Earth's rotation vector over the last century estimated from geodetic and astronomic measurements] and argued that they could all be fit by a model of ongoing glacial isostatic adjustment (GIA) associated with the last ice age. Second, he demonstrated that prevailing estimates of the 20th century GMSL rise (~1.5 to 2.0 mm/year), after correction for the maximum signal from ocean thermal expansion, implied mass flux from ice sheets and glaciers at a level that would grossly misfit the residual GIA-corrected observations of Earth's rotation. We demonstrate that the combination of lower estimates of the 20th century GMSL rise (up to 1990) improved modeling of the GIA process and that the correction of the eclipse record for a signal due to angular momentum exchange between the fluid outer core and the mantle reconciles all three Earth rotation observations. This resolution adds confidence to recent estimates of individual contributions to 20th century sea-level change and to projections of GMSL rise to the end of the 21st century based on them. PMID- 26824057 TI - Regulated lysosomal exocytosis mediates cancer progression. AB - Understanding how tumor cells transition to an invasive and drug-resistant phenotype is central to cancer biology, but the mechanisms underlying this transition remain unclear. We show that sarcomas gain these malignant traits by inducing lysosomal exocytosis, a ubiquitous physiological process. During lysosomal exocytosis, the movement of exocytic lysosomes along the cytoskeleton and their docking at the plasma membrane involve LAMP1, a sialylated membrane glycoprotein and target of the sialidase NEU1. Cleavage of LAMP1 sialic acids by NEU1 limits the extent of lysosomal exocytosis. We found that by down-regulation of NEU1 and accumulation of oversialylated LAMP1, tumor cells exacerbate lysosomal exocytosis of soluble hydrolases and exosomes. This facilitates matrix invasion and propagation of invasive signals, and purging of lysosomotropic chemotherapeutics. In Arf (-/-) mice, Neu1 haploinsufficiency fostered the development of invasive, pleomorphic sarcomas, expressing epithelial and mesenchymal markers, and lysosomal exocytosis effectors, LAMP1 and Myosin-11. These features are analogous to those of metastatic, pleomorphic human sarcomas, where low NEU1 levels correlate with high expression of lysosomal exocytosis markers. In a therapeutic proof of principle, we demonstrate that inhibiting lysosomal exocytosis reversed invasiveness and chemoresistance in aggressive sarcoma cells. Thus, we reveal that this unconventional, lysosome-regulated pathway plays a primary role in tumor progression and chemoresistance. PMID- 26824059 TI - Hacking the Bell test using classical light in energy-time entanglement-based quantum key distribution. AB - Photonic systems based on energy-time entanglement have been proposed to test local realism using the Bell inequality. A violation of this inequality normally also certifies security of device-independent quantum key distribution (QKD) so that an attacker cannot eavesdrop or control the system. We show how this security test can be circumvented in energy-time entangled systems when using standard avalanche photodetectors, allowing an attacker to compromise the system without leaving a trace. We reach Bell values up to 3.63 at 97.6% faked detector efficiency using tailored pulses of classical light, which exceeds even the quantum prediction. This is the first demonstration of a violation-faking source that gives both tunable violation and high faked detector efficiency. The implications are severe: the standard Clauser-Horne-Shimony-Holt inequality cannot be used to show device-independent security for energy-time entanglement setups based on Franson's configuration. However, device-independent security can be reestablished, and we conclude by listing a number of improved tests and experimental setups that would protect against all current and future attacks of this type. PMID- 26824060 TI - Compositional mantle layering revealed by slab stagnation at ~1000-km depth. AB - Improved constraints on lower-mantle composition are fundamental to understand the accretion, differentiation, and thermochemical evolution of our planet. Cosmochemical arguments indicate that lower-mantle rocks may be enriched in Si relative to upper-mantle pyrolite, whereas seismic tomography images suggest whole-mantle convection and hence appear to imply efficient mantle mixing. This study reconciles cosmochemical and geophysical constraints using the stagnation of some slab segments at ~1000-km depth as the key observation. Through numerical modeling of subduction, we show that lower-mantle enrichment in intrinsically dense basaltic lithologies can render slabs neutrally buoyant in the uppermost lower mantle. Slab stagnation (at depths of ~660 and ~1000 km) and unimpeded slab sinking to great depths can coexist if the basalt fraction is ~8% higher in the lower mantle than in the upper mantle, equivalent to a lower-mantle Mg/Si of ~1.18. Global-scale geodynamic models demonstrate that such a moderate compositional gradient across the mantle can persist can in the presence of whole mantle convection. PMID- 26824061 TI - Connecting multiple spatial scales to decode the population activity of grid cells. AB - Mammalian grid cells fire when an animal crosses the points of an imaginary hexagonal grid tessellating the environment. We show how animals can navigate by reading out a simple population vector of grid cell activity across multiple spatial scales, even though neural activity is intrinsically stochastic. This theory of dead reckoning explains why grid cells are organized into discrete modules within which all cells have the same lattice scale and orientation. The lattice scale changes from module to module and should form a geometric progression with a scale ratio of around 3/2 to minimize the risk of making large scale errors in spatial localization. Such errors should also occur if intermediate-scale modules are silenced, whereas knocking out the module at the smallest scale will only affect spatial precision. For goal-directed navigation, the allocentric grid cell representation can be readily transformed into the egocentric goal coordinates needed for planning movements. The goal location is set by nonlinear gain fields that act on goal vector cells. This theory predicts neural and behavioral correlates of grid cell readout that transcend the known link between grid cells of the medial entorhinal cortex and place cells of the hippocampus. PMID- 26824062 TI - Bioinspired large-scale aligned porous materials assembled with dual temperature gradients. AB - Natural materials, such as bone, teeth, shells, and wood, exhibit outstanding properties despite being porous and made of weak constituents. Frequently, they represent a source of inspiration to design strong, tough, and lightweight materials. Although many techniques have been introduced to create such structures, a long-range order of the porosity as well as a precise control of the final architecture remain difficult to achieve. These limitations severely hinder the scale-up fabrication of layered structures aimed for larger applications. We report on a bidirectional freezing technique to successfully assemble ceramic particles into scaffolds with large-scale aligned, lamellar, porous, nacre-like structure and long-range order at the centimeter scale. This is achieved by modifying the cold finger with a polydimethylsiloxane (PDMS) wedge to control the nucleation and growth of ice crystals under dual temperature gradients. Our approach could provide an effective way of manufacturing novel bioinspired structural materials, in particular advanced materials such as composites, where a higher level of control over the structure is required. PMID- 26824063 TI - Engineering a nanopore with co-chaperonin function. AB - The emergence of an enzymatic function can reveal functional insights and allows the engineering of biological systems with enhanced properties. We engineered an alpha hemolysin nanopore to function as GroES, a protein that, in complex with GroEL, forms a two-stroke protein-folding nanomachine. The transmembrane co chaperonin was prepared by recombination of GroES functional elements with the nanopore, suggesting that emergent functions in molecular machines can be added bottom-up by incorporating modular elements into preexisting protein scaffolds. The binding of a single-ring version of GroEL to individual GroES nanopores prompted large changes to the unitary nanopore current, most likely reflecting the allosteric transitions of the chaperonin apical domains. One of the GroEL induced current levels showed fast fluctuations (<1 ms), a characteristic that might be instrumental for efficient substrate encapsulation or folding. In the presence of unfolded proteins, the pattern of current transitions changed, suggesting a possible mechanism in which the free energy of adenosine triphosphate binding and hydrolysis is expended only when substrate proteins are occupied. PMID- 26824064 TI - Mechanisms of murine cerebral malaria: Multimodal imaging of altered cerebral metabolism and protein oxidation at hemorrhage sites. AB - Using a multimodal biospectroscopic approach, we settle several long-standing controversies over the molecular mechanisms that lead to brain damage in cerebral malaria, which is a major health concern in developing countries because of high levels of mortality and permanent brain damage. Our results provide the first conclusive evidence that important components of the pathology of cerebral malaria include peroxidative stress and protein oxidation within cerebellar gray matter, which are colocalized with elevated nonheme iron at the site of microhemorrhage. Such information could not be obtained previously from routine imaging methods, such as electron microscopy, fluorescence, and optical microscopy in combination with immunocytochemistry, or from bulk assays, where the level of spatial information is restricted to the minimum size of tissue that can be dissected. We describe the novel combination of chemical probe-free, multimodal imaging to quantify molecular markers of disturbed energy metabolism and peroxidative stress, which were used to provide new insights into understanding the pathogenesis of cerebral malaria. In addition to these mechanistic insights, the approach described acts as a template for the future use of multimodal biospectroscopy for understanding the molecular processes involved in a range of clinically important acute and chronic (neurodegenerative) brain diseases to improve treatment strategies. PMID- 26824065 TI - A new time tree reveals Earth history's imprint on the evolution of modern birds. AB - Determining the timing of diversification of modern birds has been difficult. We combined DNA sequences of clock-like genes for most avian families with 130 fossil birds to generate a new time tree for Neornithes and investigated their biogeographic and diversification dynamics. We found that the most recent common ancestor of modern birds inhabited South America around 95 million years ago, but it was not until the Cretaceous-Paleogene transition (66 million years ago) that Neornithes began to diversify rapidly around the world. Birds used two main dispersion routes: reaching the Old World through North America, and reaching Australia and Zealandia through Antarctica. Net diversification rates increased during periods of global cooling, suggesting that fragmentation of tropical biomes stimulated speciation. Thus, we found pervasive evidence that avian evolution has been influenced by plate tectonics and environmental change, two basic features of Earth's dynamics. PMID- 26824066 TI - Active quantum plasmonics. AB - The ability of localized surface plasmons to squeeze light and engineer nanoscale electromagnetic fields through electron-photon coupling at dimensions below the wavelength has turned plasmonics into a driving tool in a variety of technological applications, targeting novel and more efficient optoelectronic processes. In this context, the development of active control of plasmon excitations is a major fundamental and practical challenge. We propose a mechanism for fast and active control of the optical response of metallic nanostructures based on exploiting quantum effects in subnanometric plasmonic gaps. By applying an external dc bias across a narrow gap, a substantial change in the tunneling conductance across the junction can be induced at optical frequencies, which modifies the plasmonic resonances of the system in a reversible manner. We demonstrate the feasibility of the concept using time dependent density functional theory calculations. Thus, along with two dimensional structures, metal nanoparticle plasmonics can benefit from the reversibility, fast response time, and versatility of an active control strategy based on applied bias. The proposed electrical manipulation of light using quantum plasmonics establishes a new platform for many practical applications in optoelectronics. PMID- 26824067 TI - Defaunation affects carbon storage in tropical forests. AB - Carbon storage is widely acknowledged as one of the most valuable forest ecosystem services. Deforestation, logging, fragmentation, fire, and climate change have significant effects on tropical carbon stocks; however, an elusive and yet undetected decrease in carbon storage may be due to defaunation of large seed dispersers. Many large tropical trees with sizeable contributions to carbon stock rely on large vertebrates for seed dispersal and regeneration, however many of these frugivores are threatened by hunting, illegal trade, and habitat loss. We used a large data set on tree species composition and abundance, seed, fruit, and carbon-related traits, and plant-animal interactions to estimate the loss of carbon storage capacity of tropical forests in defaunated scenarios. By simulating the local extinction of trees that depend on large frugivores in 31 Atlantic Forest communities, we found that defaunation has the potential to significantly erode carbon storage even when only a small proportion of large seeded trees are extirpated. Although intergovernmental policies to reduce carbon emissions and reforestation programs have been mostly focused on deforestation, our results demonstrate that defaunation, and the loss of key ecological interactions, also poses a serious risk for the maintenance of tropical forest carbon storage. PMID- 26824068 TI - All-polymeric control of nanoferronics. AB - In the search for light and flexible nanoferronics, significant research effort is geared toward discovering the coexisting magnetic and electric orders in crystalline charge-transfer complexes. We report the first example of multiferroicity in centimeter-sized crystalline polymeric charge-transfer superstructures that grow at the liquid-air interface and are controlled by the regioregularity of the polymeric chain. The charge order-driven ferroic mechanism reveals spontaneous and hysteretic polarization and magnetization at the donor acceptor interface. The charge transfer and ordering in the ferroic assemblies depend critically on the self-organizing and molecular packing of electron donors and acceptors. The invention described here not only represents a new coupling mechanism of magnetic and electric ordering but also creates a new class of emerging all-organic nanoferronics. PMID- 26824069 TI - Robust bidirectional links for photonic quantum networks. AB - Optical fibers are widely used as one of the main tools for transmitting not only classical but also quantum information. We propose and report an experimental realization of a promising method for creating robust bidirectional quantum communication links through paired optical polarization-maintaining fibers. Many limitations of existing protocols can be avoided with the proposed method. In particular, the path and polarization degrees of freedom are combined to deterministically create a photonic decoherence-free subspace without the need for any ancillary photon. This method is input state-independent, robust against dephasing noise, postselection-free, and applicable bidirectionally. To rigorously quantify the amount of quantum information transferred, the optical fibers are analyzed with the tools developed in quantum communication theory. These results not only suggest a practical means for protecting quantum information sent through optical quantum networks but also potentially provide a new physical platform for enriching the structure of the quantum communication theory. PMID- 26824070 TI - Chemical synthesis of erythropoietin glycoforms for insights into the relationship between glycosylation pattern and bioactivity. AB - The role of sialyloligosaccharides on the surface of secreted glycoproteins is still unclear because of the difficulty in the preparation of sialylglycoproteins in a homogeneous form. We selected erythropoietin (EPO) as a target molecule and designed an efficient synthetic strategy for the chemical synthesis of a homogeneous form of five EPO glycoforms varying in glycosylation position and the number of human-type biantennary sialyloligosaccharides. A segment coupling strategy performed by native chemical ligation using six peptide segments including glycopeptides yielded homogeneous EPO glycopeptides, and folding experiments of these glycopeptides afforded the correctly folded EPO glycoforms. In an in vivo erythropoiesis assay in mice, all of the EPO glycoforms displayed biological activity, in particular the EPO bearing three sialyloligosaccharides, which exhibited the highest activity. Furthermore, we observed that the hydrophilicity and biological activity of the EPO glycoforms varied depending on the glycosylation pattern. This knowledge will pave the way for the development of homogeneous biologics by chemical synthesis. PMID- 26824071 TI - Data-driven modeling of solar-powered urban microgrids. AB - Distributed generation takes center stage in today's rapidly changing energy landscape. Particularly, locally matching demand and generation in the form of microgrids is becoming a promising alternative to the central distribution paradigm. Infrastructure networks have long been a major focus of complex networks research with their spatial considerations. We present a systemic study of solar-powered microgrids in the urban context, obeying real hourly consumption patterns and spatial constraints of the city. We propose a microgrid model and study its citywide implementation, identifying the self-sufficiency and temporal properties of microgrids. Using a simple optimization scheme, we find microgrid configurations that result in increased resilience under cost constraints. We characterize load-related failures solving power flows in the networks, and we show the robustness behavior of urban microgrids with respect to optimization using percolation methods. Our findings hint at the existence of an optimal balance between cost and robustness in urban microgrids. PMID- 26824072 TI - Social behavior shapes the chimpanzee pan-microbiome. AB - Animal sociality facilitates the transmission of pathogenic microorganisms among hosts, but the extent to which sociality enables animals' beneficial microbial associations is poorly understood. The question is critical because microbial communities, particularly those in the gut, are key regulators of host health. We show evidence that chimpanzee social interactions propagate microbial diversity in the gut microbiome both within and between host generations. Frequent social interaction promotes species richness within individual microbiomes as well as homogeneity among the gut community memberships of different chimpanzees. Sampling successive generations across multiple chimpanzee families suggests that infants inherited gut microorganisms primarily through social transmission. These results indicate that social behavior generates a pan-microbiome, preserving microbial diversity across evolutionary time scales and contributing to the evolution of host species-specific gut microbial communities. PMID- 26824073 TI - Large-scale diversification without genetic isolation in nematode symbionts of figs. AB - Diversification is commonly understood to be the divergence of phenotypes accompanying that of lineages. In contrast, alternative phenotypes arising from a single genotype are almost exclusively limited to dimorphism in nature. We report a remarkable case of macroevolutionary-scale diversification without genetic divergence. Upon colonizing the island-like microecosystem of individual figs, symbiotic nematodes of the genus Pristionchus accumulated a polyphenism with up to five discrete adult morphotypes per species. By integrating laboratory and field experiments with extensive genotyping of individuals, including the analysis of 49 genomes from a single species, we show that rapid filling of potential ecological niches is possible without diversifying selection on genotypes. This uncoupling of morphological diversification and speciation in fig associated nematodes has resulted from a remarkable expansion of discontinuous developmental plasticity. PMID- 26824075 TI - Monitoring transient changes within overpressured regions of subduction zones using ambient seismic noise. AB - In subduction zones, elevated pore fluid pressure, generally linked to metamorphic dehydration reactions, has a profound influence on the mechanical behavior of the plate interface and forearc crust through its control on effective stress. We use seismic noise-based monitoring to characterize seismic velocity variations following the 2012 Nicoya Peninsula, Costa Rica earthquake [M w (moment magnitude) 7.6] that we attribute to the presence of pressurized pore fluids. Our study reveals a strong velocity reduction (~0.6%) in a region where previous work identified high forearc pore fluid pressure. The depth of this velocity reduction is constrained to be below 5 km and therefore not the result of near-surface damage due to strong ground motions; rather, we posit that it is caused by fracturing of the fluid-pressurized weakened crust due to dynamic stresses. Although pressurized fluids have been implicated in causing coseismic velocity reductions beneath the Japanese volcanic arc, this is the first report of a similar phenomenon in a subduction zone setting. It demonstrates the potential to identify pressurized fluids in subduction zones using temporal variations of seismic velocity inferred from ambient seismic noise correlations. PMID- 26824074 TI - Conditional iron and pH-dependent activity of a non-enzymatic glycolysis and pentose phosphate pathway. AB - Little is known about the evolutionary origins of metabolism. However, key biochemical reactions of glycolysis and the pentose phosphate pathway (PPP), ancient metabolic pathways central to the metabolic network, have non-enzymatic pendants that occur in a prebiotically plausible reaction milieu reconstituted to contain Archean sediment metal components. These non-enzymatic reactions could have given rise to the origin of glycolysis and the PPP during early evolution. Using nuclear magnetic resonance spectroscopy and high-content metabolomics that allowed us to measure several thousand reaction mixtures, we experimentally address the chemical logic of a metabolism-like network constituted from these non-enzymatic reactions. Fe(II), the dominant transition metal component of Archean oceanic sediments, has binding affinity toward metabolic sugar phosphates and drives metabolism-like reactivity acting as both catalyst and cosubstrate. Iron and pH dependencies determine a metabolism-like network topology and comediate reaction rates over several orders of magnitude so that the network adopts conditional activity. Alkaline pH triggered the activity of the non enzymatic PPP pendant, whereas gentle acidic or neutral conditions favored non enzymatic glycolytic reactions. Fe(II)-sensitive glycolytic and PPP-like reactions thus form a chemical network mimicking structural features of extant carbon metabolism, including topology, pH dependency, and conditional reactivity. Chemical networks that obtain structure and catalysis on the basis of transition metals found in Archean sediments are hence plausible direct precursors of cellular metabolic networks. PMID- 26824076 TI - Targeting NF-kappaB in glioblastoma: A therapeutic approach. AB - Glioblastoma multiforme (GBM) is the most common and lethal form of intracranial tumor. We have established a lentivirus-induced mouse model of malignant gliomas, which faithfully captures the pathophysiology and molecular signature of mesenchymal human GBM. RNA-Seq analysis of these tumors revealed high nuclear factor kappaB (NF-kappaB) activation showing enrichment of known NF-kappaB target genes. Inhibition of NF-kappaB by either depletion of IkappaB kinase 2 (IKK2), expression of a IkappaBalphaM super repressor, or using a NEMO (NF-kappaB essential modifier)-binding domain (NBD) peptide in tumor-derived cell lines attenuated tumor proliferation and prolonged mouse survival. Timp1, one of the NF kappaB target genes significantly up-regulated in GBM, was identified to play a role in tumor proliferation and growth. Inhibition of NF-kappaB activity or silencing of Timp1 resulted in slower tumor growth in both mouse and human GBM models. Our results suggest that inhibition of NF-kappaB activity or targeting of inducible NF-kappaB genes is an attractive therapeutic approach for GBM. PMID- 26824077 TI - Shape memory polymer network with thermally distinct elasticity and plasticity. AB - Stimuli-responsive materials with sophisticated yet controllable shape-changing behaviors are highly desirable for real-world device applications. Among various shape-changing materials, the elastic nature of shape memory polymers allows fixation of temporary shapes that can recover on demand, whereas polymers with exchangeable bonds can undergo permanent shape change via plasticity. We integrate the elasticity and plasticity into a single polymer network. Rational molecular design allows these two opposite behaviors to be realized at different temperature ranges without any overlap. By exploring the cumulative nature of the plasticity, we demonstrate easy manipulation of highly complex shapes that is otherwise extremely challenging. The dynamic shape-changing behavior paves a new way for fabricating geometrically complex multifunctional devices. PMID- 26824078 TI - Simultaneous T1 and T2 Brain Relaxometry in Asymptomatic Volunteers using Magnetic Resonance Fingerprinting. AB - Magnetic resonance fingerprinting (MRF) is a method of image acquisition that produces multiple MR parametric maps from a single scan. Here, we describe the normal range and progression of MRF-derived relaxometry values with age in healthy individuals. 56 normal volunteers (ages 11-71 years, M:F 24:32) were scanned. Regions of interest were drawn on T1 and T2 maps in 38 areas, including lobar and deep white matter, deep gray nuclei, thalami and posterior fossa structures. Relaxometry differences were assessed using a forward stepwise selection of a baseline model including either gender, age, or both, where variables were included if they contributed significantly (p<0.05). Additionally, differences in regional anatomy, including comparisons between hemispheres and between anatomical subcomponents, were assessed by paired t-tests. Using this protocol, MRF-derived T1 and T2 in frontal WM regions were found to increase in with age, while occipital and temporal regions remained relatively stable. Deep gray nuclei, including substantia nigra, were found to have age-related decreases in relaxometry. Gender differences were observed in T1 and T2 of temporal regions, cerebellum and pons. Males were also found to have more rapid age related changes in frontal and parietal WM. Regional differences were identified between hemispheres, between genu and splenium of corpus callosum, and between posteromedial and anterolateral thalami. In conclusion, MRF quantification can measure relaxometry trends in healthy individuals that are in agreement with current understanding of neuroanatomy and neurobiology, and has the ability to uncover additional patterns that have not yet been explored. PMID- 26824080 TI - Zebra Crossing Spotter: Automatic Population of Spatial Databases for Increased Safety of Blind Travelers. AB - In this paper we propose a computer vision-based technique that mines existing spatial image databases for discovery of zebra crosswalks in urban settings. Knowing the location of crosswalks is critical for a blind person planning a trip that includes street crossing. By augmenting existing spatial databases (such as Google Maps or OpenStreetMap) with this information, a blind traveler may make more informed routing decisions, resulting in greater safety during independent travel. Our algorithm first searches for zebra crosswalks in satellite images; all candidates thus found are validated against spatially registered Google Street View images. This cascaded approach enables fast and reliable discovery and localization of zebra crosswalks in large image datasets. While fully automatic, our algorithm could also be complemented by a final crowdsourcing validation stage for increased accuracy. PMID- 26824079 TI - Adiposity throughout adulthood and risk of sudden cardiac death in women. AB - BACKGROUND: Sudden cardiac death (SCD) is often the first manifestation of coronary heart disease (CHD) among women. Data regarding BMI and risk of SCD are limited and conflicting. OBJECTIVES: We examined the association of BMI repeatedly measured over 32 years and BMI during early and mid-adulthood with risk of SCD in the Nurses' Health Study. METHODS: We prospectively followed 72,484 women free of chronic disease from 1980-2012. We ascertained adult height, current weight, and weight at age 18 at baseline and updated weight biennially. The primary endpoint was SCD (n=445). RESULTS: When updated biennially, higher BMI was associated with greater SCD risk after adjusting for confounders (p, linear trend: <0.001). Compared to a BMI of 21.0-22.9, the multivariate RR (95%CI) of SCD was 1.46 (1.05, 2.04) for BMI 25.0-29.9, 1.46 (1.00, 2.13) for BMI 30.0-34.9 and 2.18 (1.44, 3.28) for BMI >=35.0. Among women with a BMI >=35.0, SCD remained elevated even after adjustment for interim development of CHD and other mediators (RR: 1.72; 95%CI: 1.13, 2.60). In contrast, the association between BMI and fatal CHD risk was completely attenuated after adjustment for mediators. The magnitude of the association between BMI and SCD was greater when BMI was assessed at baseline or at age 18, at which time SCD risk remained significantly elevated at BMI>=30 after adjustment for mediators. CONCLUSIONS: Higher BMI was associated with greater risk of SCD, particularly when assessed earlier in adulthood. Strategies to maintain a healthy weight throughout adulthood may minimize SCD incidence. PMID- 26824081 TI - Appliance Displays: Accessibility Challenges and Proposed Solutions. AB - People who are blind or visually impaired face difficulties using a growing array of everyday appliances because they are equipped with inaccessible electronic displays. We report developments on our "Display Reader" smartphone app, which uses computer vision to help a user acquire a usable image of a display and have the contents read aloud, to address this problem. Drawing on feedback from past and new studies with visually impaired volunteer participants, as well as from blind accessibility experts, we have improved and simplified our user interface and have also added the ability to read seven-segment digit displays. Our system works fully automatically and in real time, and we compare it with general purpose assistive apps such as Be My Eyes, which recruit remote sighted assistants (RSAs) to answer questions about video captured by the user. Our discussions and preliminary experiment highlight the advantages and disadvantages of fully automatic approaches compared with RSAs, and suggest possible hybrid approaches to investigate in the future. PMID- 26824082 TI - Short-term effects of Verbena officinalis Linn decoction on patients suffering from chronic generalized gingivitis: Double-blind randomized controlled multicenter clinical trial. AB - OBJECTIVE: To evaluate the clinical efficacy of Verbena officinalis Linn decoction for patients with chronic generalized gingivitis in a double-blind randomized controlled multicenter clinical trial. METHOD AND MATERIALS: The patients in the test group and the control group were instructed to brush and floss. Additionally, the patients in the test group were asked to rinse their mouths with a V officinalis L decoction. The primary clinical outcome was the Gingival Index (GI). The GI and Plaque Index (PI) were measured at baseline (day 0), day 14, and day 28. RESULTS: Two hundred and sixty patients participated (control group = 130, and test group = 130). The clinical features of both the test and control groups were improved progressively throughout the time durations of day 0, day 14, and day 28 represented by highly significant decreases in both GI and PI (P < .001). The Mann-Whitney test revealed significant differences between the control and test groups for GI and PI at the 14-day examination and the 28-day examination (P < .001). At the beginning of the clinical trial, nonsignificant clinical differences were found following the statistical analyses of both GI (P = .981) and PI (P = .920) between the test and control groups. CONCLUSIONS: The tested V officinalis L decoction demonstrated efficacy in reducing tested indices and thus has a promising ameliorative effect for treating patients with chronic generalized gingivitis. CLINICAL SIGNIFICANCE: V officinalis L decoction has good clinical results with no adverse effects. PMID- 26824083 TI - Isolated mucosal fenestration with localized gingival recession: Closure with an acellular dermal graft. A rare case report with two years' follow-up. AB - Mucosal fenestrations are rarely encountered in clinical practice, and as such their management is not often reported. Their treatment might be further complicated due to a communication with the oral environment, making them more susceptible to accumulation of debris, plaque, and calculus, thereby reducing the probability of mucosal renewal. The aim of the present case report is to highlight one such rare clinical scenario and its apt and effective management. Surgical management of an uncommon presentation of concomitant gingival recession with an isolated mucosal fenestration in an atypical location, with an allograft matrix is presented here with 2 years' follow-up. A review of the literature reveals no previous application of AlloDerm graft for the management of a similar situation. PMID- 26824084 TI - Bisphosphonates and dental implants: A meta-analysis. AB - OBJECTIVE: To test the null hypothesis of no difference in the implant failure rates, marginal bone loss, and postoperative infection for patients receiving or not receiving bisphosphonates, against the alternative hypothesis of a difference. METHOD AND MATERIALS: An electronic search was undertaken in October 2015 in PubMed/Medline, Web of Science, and Embase, plus hand-searching and databases of clinical trials. Eligibility criteria included clinical human studies, either randomized or not. RESULTS: A total of 18 publications were included in the review. Concerning implant failure, the meta-analysis found a risk ratio of 1.73 (95% confidence interval [CI] 1.21-2.48, P = .003) for patients taking bisphosphonates, when compared to patients not taking the medicament. The probability of an implant failure in patients taking bisphosphonates was estimated to be 1.5% (0.015, 95% CI 0.006- 0.023, standard error [SE] 0.004, P < .001). It cannot be suggested that bisphosphonates may affect the marginal bone loss of dental implants, due to a limited number of studies reporting this outcome. Due to a lack of sufficient information, meta analysis for the outcome "postoperative infection" was not performed. CONCLUSION: The results of the present study cannot suggest that the insertion of dental implants in patients taking BPs affects the implant failure rates, due to a limited number of published studies, all characterized by a low level of specificity, and most of them dealing with a limited number of cases without a proper control group. Therefore, the real effect of BPs on the osseointegration and survival of dental implants is still not well established. PMID- 26824085 TI - Impact of digital intraoral scan strategies on the impression accuracy using the TRIOS Pod scanner. AB - OBJECTIVES: Little information is available on the impact of different scan strategies on the accuracy of full-arch scans with intraoral scanners. The aim of this in-vitro study was to investigate the trueness and precision of full-arch maxillary digital impressions comparing three scan strategies. METHOD AND MATERIALS: Three scan strategies (A, B, and C) were applied each five times on one single model (A, first buccal surfaces, return from occlusal-palatal; B, first occlusal-palatal, return buccal; C, S-type one-way). The TRIOS Pod scanner (3shape, Copenhagen, Denmark) with a color detector was used for these digital impressions. A cast of a maxillary dentate jaw was fabricated and scanned with an industrial reference scanner. This full-arch data record was digitally superimposed with the test scans (trueness) and within-group comparison was performed for each group (precision). The values within the 90/10 percentiles from the digital superimposition were used for calculation and group comparisons with nonparametric tests (ANOVA, post-hoc Bonferroni). RESULTS: The trueness (mean +/- standard deviation) was 17.9 +/- 16.4 MUm for scan strategy A, 17.1 +/- 13.7 MUm for B, and 26.8 +/- 14.7 MUm for C without statistically significant difference. The precision was lowest for scan strategy A (35.0 +/- 51.1 MUm) and significantly different to B (7.9 +/- 5.6 MUm) and C (8.5 +/- 6.3 MUm). CONCLUSIONS: Scan strategy B may be recommended as it provides the highest trueness and precision in full-arch scans and therefore minimizes inaccuracies in the final reconstruction. PMID- 26824086 TI - Effect of apex size on the leakage of gutta-percha and sealer-filled root canals. AB - OBJECTIVES: There are no data comparing coronal leakage of teeth prepared to different apical sizes and obturated with gutta-percha and sealer. The aim of this study was to investigate the effect of apical preparation size on the leakage of obturated root canals. Large apical openings are encountered as a result of pulp necrosis in immature teeth, apical resorption, or over-enlargement of the apical foramen. Complete cleaning, shaping, obturation, and apical seal of root canal systems are essential for the success of root canal treatment. METHOD AND MATERIALS: One hundred twenty-five extracted human teeth were divided into groups containing 25 samples each and prepared to apical file sizes 30, 40, 50, 60, and 70. Twenty teeth served as positive and negative controls. Obturation was completed with gutta-percha and sealer via warm vertical compaction. Bacterial leakage was investigated after 112 days using Proteus vulgaris. Data were analyzed via independent-samples Kruskal-Wallis test. RESULTS: The average time for leakage of apical preparation sizes 30, 40, 50, 60, and 70 were 57.5, 52.4, 47.2, 37.5, and 28.4 days, respectively. Significant differences in leakage were observed between apical preparation sizes 70 versus 30, 70 versus 40, 70 versus 50, as well as 60 versus 30. A trend for more leakage occurred when apical preparation sizes exceeded size 60. CONCLUSIONS: Based on these results, it appears leakage of gutta-percha and sealer as obturation materials increases when apical preparation size exceeds 60. Consideration should be given to using sealing materials other than gutta-percha and sealer when the apex size exceeds 60. PMID- 26824087 TI - A combined peri-implant plastic surgery approach for implants in the esthetic zone using a novel technique: A series of 10 cases. AB - OBJECTIVE: In this study, 12-month follow-up clinical results of a combined peri implant plastic surgery approach for hard and soft tissue augmentation in implant rehabilitation in the esthetic zone are presented. METHOD AND MATERIALS: Ten individuals who required extraction due to severe periodontal destruction in the maxillary and mandibular area were included in the study. Implant surgery was performed in the same session as the combined peri-implant plastic surgeries, which involved guided bone regeneration and free periosteal grafts. Prosthetic treatment was administered in the sixth month following the surgeries. RESULTS: Hard and soft tissue augmentation with sufficient keratinized mucosa width (>= 2 mm) was achieved with the combined surgical approaches. Pleasing esthetic results were obtained by careful positioning of the implants. CONCLUSIONS: In implant rehabilitation, in cases where there are insufficient hard and soft tissues in the esthetic zone, a combined peri-implant plastic surgery approach not only enables the ideal implant position where both function and esthetics are ensured but also provides effective protection of peri-implant tissue health. PMID- 26824088 TI - Manipulating the inter pillar gap in pillar array ultra-thin layer planar chromatography platforms. AB - An advantage of separation platforms based on deterministic micro- and nano fabrications, relative to traditional systems based on packed beds of particles, is the exquisite control of all morphological parameters. For example, with planar platforms based on lithographically-prepared pillar arrays, the size, shape, height, geometric arrangement, and inter pillar gaps can be independently adjusted. Since the inter pillar gap is expected to be important in determining resistance to mass transfer in the mobile phase as well as the flow rate, which influences the mass transfer effect and axial diffusion, we herein study the effect of reducing inter pillar gaps on capillary action-based flow and band dispersion. Atomic layer deposition is used to narrow the gap between the pillars for photo-lithographically defined pillar arrays. The plate height of gap adjusted arrays is modeled based on predicted and observed flow rates. A reduction in the flow rate with smaller gaps hinders the efficiency in the modeled case and is correlated with actual separations. A conclusion is drawn that simultaneously reducing both the gap and the pillar diameter is the best approach in terms of improving the chromatographic efficiency. PMID- 26824089 TI - Monitoring polydispersity by NMR diffusometry with tailored norm regularisation and moving-frame processing. AB - Nuclear magnetic resonance (NMR) is currently one of the main analytical techniques applied in numerous branches of chemistry. Furthermore, NMR has been proven to be useful to follow in situ reactions occurring on a time scale of hours and days. For complicated mixtures, NMR experiments providing diffusion coefficients are particularly advantageous. However, the inverse Laplace transform (ILT) that is used to extract the distribution of diffusion coefficients from an NMR signal is known to be unstable and vulnerable to noise. Numerous regularisation techniques to circumvent this problem have been proposed. In our recent study, we proposed a method based on sparsity-enforcing l1-norm minimisation. This approach, which is referred to as ITAMeD, has been successful but limited to samples with a 'discrete' distribution of diffusion coefficients. In this paper, we propose a generalisation of ITAMeD using a tailored lp-norm (1 <= p <= 2) to process, in particular, signals arising from 'polydisperse' samples. The performance of our method was tested on simulations and experimental datasets of polyethylene oxides with varying polydispersity indices. Finally, we applied our new method to monitor diffusion coefficient and polydispersity changes of heparin undergoing enzymatic degradation in real time. PMID- 26824090 TI - Quantitative electrochemical metalloimmunoassay for TFF3 in urine using a paper analytical device. AB - We report a paper-based assay platform for the detection of the kidney disease marker Trefoil Factor 3 (TFF3) in human urine. The sensor is based on a quantitative metalloimmunoassay that can determine TFF3 concentrations via electrochemical detection of environmentally stable silver nanoparticle (AgNP) labels attached to magnetic microbeads via a TFF3 immunosandwich. The paper electroanalytical device incorporates two preconcentration steps that make it possible to detect concentrations of TFF3 in human urine at the low end of the target TFF3 concentration range (0.03-7.0 MUg mL(-1)). Importantly, the paper device provides a level of accuracy for TFF3 determination in human urine equivalent to that of a commercial kit. The paper sensor has a dynamic range of ~2.5 orders of magnitude, only requires a simple, one-step incubation protocol, and is fast, requiring only 10 min to complete. The cost of the materials at the prototypic laboratory scale, excluding reagents, is just US$0.42. PMID- 26824091 TI - Sample stage designed for force modulation microscopy using a tip-mounted AFM scanner. AB - Among the modes of scanning probe microscopy (SPM), force modulation microscopy (FMM) is often used to acquire mechanical properties of samples concurrent with topographic information. The FMM mode is useful for investigations with polymer and organic thin film samples. Qualitative evaluation of the mixed domains of co polymers or composite films can often be accomplished with high resolution using FMM phase and amplitude images. We have designed and tested a sample stage for FMM constructed of machined polycarbonate. A generic design enables FMM experiments for instrument configurations with a tip-mounted SPM scanner. A piezoactuator within the sample stage was used to drive the sample to vibrate in the z-direction according to selected parameters. To evaluate the FMM sample stage, we tested samples of known composition with nanoscale dimensions for increasingly complex surface morphologies. Excellent resolution was achieved in ambient conditions using the home-constructed sample stage, as revealed for complex surfaces or multi-component samples. Test structures of nanoholes within a film of organosilanes provided the simplest platform with two distinct surface domains. Ring-shaped nanostructures prepared on Si(111) with mixed organosilanes provided three regions for evaluating FMM results. A complex sample consisting of a cyclic gel polymer containing fibril nanostructures was also tested with FMM measurements. Frequency spectra were acquired for sample domains, revealing distinct differences in local mechanical response. We demonstrate a practical approach to construct a sample stage accessory to facilitate z-sample modulation for FMM experiments with tip-mounted SPM scanners. PMID- 26824092 TI - A SERS and electrical sensor from gas-phase generated Ag nanoparticles self assembled on planar substrates. AB - Optical excitation of coupled plasmonic nanoparticles supports intense localized electromagnetic "hot-spots" which enable a variety of surface enhanced spectroscopies with the best known example being surface enhanced Raman scattering (SERS), currently of great interest for sensing applications. In this study, we present a novel SERS and electrical dual transduction chemical sensor based on gas-phase generated, negatively charged, silver nanoparticles self assembled on glass slide forming a close-packed plasmonic monolayer thin-film that supports both SERS and electrical sensing. We demonstrate broad tunability of the localized surface plasmon resonance (LSPR) of the close-packed plasmonic nanoparticle monolayer thin-film sensors through control of the nanoparticle (NP) deposition time which directly influences the plasmonic coupling between neghibouring NPs. This broad tunability supports strong SERS activity from visible to near infrared (NIR) excitation wavelengths. We performed SERS and electrical measurements of a non-resonant molecule 4-mercaptobenzonitrile (4-MBN) as a sample Raman reporter molecule to determine the SERS enhancement factor of our SERS substrate. We measured an average SERS enhancement factor of 10(7) from our close-packed plasmonic nanoparticle monolayer thin-film sensor. Films which were grown below or above one nanoparticle monolayer both exhibited significantly lower SERS performance in one or more of SERS enhancement factor (EF), uniformity or repeatability. Our close-packed plasmonic nanoparticle monolayer thin-film sensors are highly uniform from point-to-point across the entire substrate and showed good reproducibility from batch-to-batch. These qualities are highly desirable for quantifiable detection of chemical and biological molecules. As an example application, this type of substrates provides an affordable and reliable sensing and identification capability for combatting new and emerging chemical and biological threats in support of security applications. PMID- 26824093 TI - Introducing the Gastroenterologist-Accountable Professionalism in Practice (G APP) pathway: bridging the G-APP-replacing MOC with a model for lifelong learning and accountability. PMID- 26824094 TI - [Sulodexide in conservative treatment of peripheral arterial diseases]. AB - Presented in the article is a review of the literature, analysing principles of conservative therapy of patients with obliterating diseases of lower limb arteries and most commonly used drugs to treat them, followed by discussing the mechanisms of action and efficacy of such pharmacological agents as pentoxyphyllin, cilostazol, naphthidrofuryl, aktovegin, sulodexide. Described in details are subtle mechanisms of action of sulodexide as an endothelioprotector, its clinical efficacy in intermittent claudication. PMID- 26824095 TI - Preface. PMID- 26824096 TI - [At the origin of the development of russian angiology (dedicated to the 150 birthday of academician N.P. Kravkov)]. AB - The article describes scientific activity of outstanding pharmacologist, Academician N.P. Kravkov (1865-1924) on studying dynamics of the vascular system in experiment: Using the method of isolated animal organs of animals, N.P. Kravkov discovered self-maintained periodic contractions of vessels independent of the central nervous system and not associated with cardiac contractions. On isolated animal organs (heart, kidneys, spleen, womb, pancreas and others) specialists of the laboratory of N.P. Kravkov studied vascular reactions and sensitivity of vascular zones to administration of pharmacological agents in normal conditions and on various experimental ''pathological" models. For studying physiology and pharmacology of coronary vessels irrespective of cardiac contractions masking change in their lumen N.P. Kravkov suggested his original method of cardiac arrest by means of administration of strophanthin followed by passing through vessels of the unfunctioning heart solutions of various pharmacological substances. N.P. Kravkov and !{is followers studied alterations in vascular tonicity on isolated organs of cadavers of people who had died of various diseases: tuberculosis, typhoid fever and epidemic typhus, scarlet fever, measles, diphtheria, pneumonia et cet. The scientist believed that studying the functional state of vessels on post-mortem material would make it possible to more precisely and accurately solve the problem of intravital alterations thereof N.P. Kravkov's works on physiology and pathology of'the vascular system served as the basis for the developing clinical discipline, i.e. angiology. PMID- 26824097 TI - [European venous forum (Saint-Petersburg, July 2-4, 2015)]. AB - At the beginning of July 2015 Saint-Petersburg/or several days turned out to be in the centre of events of the European Ph lebo logical Community. It became the venue for more than 800 participants of the European Venous Forum (EVF) from 60 countries of the world and 67 regions of Russia. It was for the .first time over 16 years of the existence of this European-largest phlebological organization that Russia was afforded the honour for holding the conference. The article deals with a review of the main materials presented at the Forum, as well as the most interesting trends of the development of modern phlebology. PMID- 26824098 TI - [Re: E-cigarettes--harmful or beneficial?]. PMID- 26824099 TI - RESPONSE: Unraveling the Scenes in the Complex Story of Our Patients' Health. PMID- 26824100 TI - DNA profiling in India. PMID- 26824101 TI - Uwe Sauer. PMID- 26824103 TI - MICROBIOLOGY: The strain in metagenomics. PMID- 26824102 TI - Simple linear regression. PMID- 26824104 TI - IMAGING: Super-resolution in live cells. PMID- 26824105 TI - NEUROSCIENCE: Targeting spines. PMID- 26824106 TI - NEUROSCIENCE: Pressuring neurons into action. PMID- 26824107 TI - SYSTEMS BIOLOGY: Ancient protein complexes revealed. PMID- 26824108 TI - CELL BIOLOGY: How kinases attack signaling networks. PMID- 26824109 TI - Psychology: Faking it. PMID- 26824110 TI - Reply: To PMID 25531370. PMID- 26824111 TI - Reply. Paraoxonase: A Multifunctional Biomolecule. PMID- 26824112 TI - [Not Available]. PMID- 26824113 TI - [Not Available]. PMID- 26824114 TI - [Not Available]. PMID- 26824115 TI - [Not Available]. PMID- 26824116 TI - Author's Reply. PMID- 26824117 TI - Author's Reply. PMID- 26824118 TI - Author's Reply. PMID- 26824119 TI - Author's Reply. PMID- 26824120 TI - Author's Reply. PMID- 26824121 TI - Author's Reply. PMID- 26824122 TI - Gold Medal of the Catalan Transplantation Society to Dr. Juan Carlos Izpisua Belmonte. PMID- 26824123 TI - An interview with Donald B. Ardell. PMID- 26824124 TI - Health promotion contrarians: Luther Terry, Halbert L. Dunn, Robert F. Allen, and Edward M. Kennedy. PMID- 26824125 TI - Commentary: opposing views and civil discourse. PMID- 26824126 TI - References from game changers and contrarians. PMID- 26824127 TI - Covalent Carbene Functionalization of Graphene: Toward Chemical Band-Gap Manipulation. AB - In this work, we employ dibromocarbene (DBC) radicals to covalently functionalize solution exfoliated graphene via the formation of dibromocyclopropyl adducts. This is achieved using a basic aqueous/organic biphasic reaction mixture to decompose the DBC precursor, bromoform, in conjunction with a phase-transfer catalyst to facilitate ylide formation and carbene migration to graphene substrates. DBC-functionalized graphene (DBC-graphene) was characterized using a range of spectroscopic and analytical techniques to confirm the covalent nature of functionalization. Modified optical and electronic properties of DBC-graphene were investigated using UV-vis spectroscopy, analysis of electrical I-V transport properties, and noncontact terahertz time-domain spectroscopy. The implications of carbene functionalization of graphene are considered in the context of scalable radical functionalization methodologies for bulk-scale graphene processing and controlled band-gap manipulation of graphene. PMID- 26824128 TI - N-Acyl Dehydrotyrosines, Tyrosinase Inhibitors from the Marine Bacterium Thalassotalea sp. PP2-459. AB - Thalassotalic acids A-C and thalassotalamides A and B are new N-acyl dehydrotyrosine derivatives produced by Thalassotalea sp. PP2-459, a Gram negative bacterium isolated from a marine bivalve aquaculture facility. The structures were elucidated via a combination of spectroscopic analyses emphasizing two-dimensional NMR and high-resolution mass spectrometric data. Thalassotalic acid A (1) displays in vitro inhibition of the enzyme tyrosinase with an IC50 value (130 MUM) that compares favorably to the commercially used control compounds kojic acid (46 MUM) and arbutin (100 MUM). These are the first natural products reported from a bacterium belonging to the genus Thalassotalea. PMID- 26824129 TI - Impaired Physical Function Associated with Childhood Obesity: How Should We Intervene? AB - BACKGROUND: This study examined relationships between adiposity, physical functioning, and physical activity. METHODS: Obese (N = 107) and healthy-weight (N = 132) children aged 10-13 years underwent assessments of percent body fat (%BF, dual energy X-ray absorptiometry); knee extensor strength (KE, isokinetic dynamometry); cardiorespiratory fitness (CRF, peak oxygen uptake by cycle ergometry); physical health-related quality of life (HRQOL); and worst pain intensity and walking capacity [six-minute walk (6MWT)]. Structural equation modelling was used to assess relationships between variables. RESULTS: Moderate relationships were observed between %BF and (1) 6MWT, (2) KE strength corrected for mass, and (3) CRF relative to mass (r -0.36 to -0.69, p <= 0.007). Weak relationships were found between %BF and physical HRQOL (r -0.27, p = 0.008); CRF relative to mass and physical HRQOL (r -0.24, p = 0.003); physical activity and 6MWT (r 0.17, p = 0.004). Squared multiple correlations showed that 29.6% variance in physical HRQOL was explained by %BF, pain, and CRF relative to mass; while 28.0% variance in 6MWT was explained by %BF and physical activity. CONCLUSIONS: It appears that children with a higher body fat percentage have poorer KE strength, CRF, and overall physical functioning. Reducing percent fat appears to be the best target to improve functioning. However, a combined approach to intervention, targeting reductions in body fat percentage, reductions in pain, and improvements in physical activity and CRF may assist physical functioning. PMID- 26824130 TI - Disparities in Service Use and Expenditures for People With Intellectual and Developmental Disabilities in California in 2005 and 2013. AB - This study examined service use and expenditures for people with intellectual and developmental disabilities (IDD) living at home and in the community in California in 2005 and 2013. The number of people assessed for IDD services increased, along with the percentage of individuals who did not receive any services between 2005 and 2013. Controlling for client needs, children age 3-21 were less likely than other age groups to receive any services using logistic regressions. All racial and ethnic minority groups were less likely to receive any services than were white populations. Females, younger people, and all racial and ethnic minority groups who received services had significantly lower expenditures, with wide geographic variations. The disparities by age, gender, race/ethnicity, and geography have persisted over time in California. PMID- 26824131 TI - Learning to Apply Algebra in the Community for Adults With Intellectual Developmental Disabilities. AB - Students with intellectual and developmental disabilities (IDD) are routinely excluded from algebra and other high-level mathematics courses. High school students with IDD take courses in arithmetic and life skills rather than having an opportunity to learn algebra. Yet algebra skills can support the learning of money and budgeting skills. This study explores the feasibility of algebra instruction for adults with IDD through an experimental curriculum. Ten individuals with IDD participated in a 6-week course framing mathematics concepts within the context of everyday challenges in handling money. The article explores classroom techniques, discusses student strategies, and proposes possible avenues for future research analyzing mathematics instructional design strategies for individuals with IDD. PMID- 26824132 TI - The Physical Activity Support Needs and Strategies Scale: Its Development and Use. AB - People with intellectual disability (ID) engage in insufficient physical activity which negatively affects their health. In accordance with the present conception of ID and the supports paradigm, the current study aimed to develop and psychometrically assess an instrument examining the support needs and strategies regarding physical activity by using individuals with ID (n = 529), service providers (n = 522), and family members (n = 462) as information sources. The analysis revealed adequate reliability for the proposed instrument, with alpha values between .70 and .80, and adequate construct validity for the versions of the scale for the 3 information sources, particularly for service providers. The assessment information can be included in Individualized Support Plans and could be used to design and implement the strategies for facilitating a person's physical activity in their community. PMID- 26824133 TI - Resilience Processes Supporting Adolescents With Intellectual Disability: A Multiple Case Study. AB - Resilience, or the process of adjusting well to risk, relies on constructive collaboration between youths and their social ecologies. Although the literature details the risks of an intellectual disability (ID), there is little explanation of why some young people cope well despite these risks. Accordingly, we report a multiple case study that affords insight into the resilience of 24 adolescents with ID. Using a draw-and-talk methodology, these young people explained their resilience as enabled primarily by supportive social ecologies (which facilitated behavioral and emotional regulation, encouraged mastery, treated them as agentic beings, and offered safe spaces). Adolescents' positive orientation to their life worlds co-facilitated their resilience. These insights advance effective ways to champion the resilience of young people with ID. PMID- 26824134 TI - Systematic Review of Health Promotion Programs Focused on Behavioral Changes for People With Intellectual Disability. AB - People with intellectual disability (ID) experience high rates of chronic health problems and poor overall health compared to people without disabilities. Recent attention to health risk behaviors such as poor diet, lack of physical activity, and underuse of health care has led to the development of several programs intended to reduce disparities in this population through health promotion programs. A review of the literature was conducted focusing on programs developed to target behavioral changes in the person with ID. Thirteen studies, evaluating 10 different health promotion programs, were found. Programs varied significantly in design, targeted health change, and demonstrated effectiveness. Components of each program are systematically reviewed and recommendations made for future programs based upon the current evidence. PMID- 26824137 TI - Recovery of molybdenum, nickel and cobalt by precipitation from the acidic leachate of a mineral sludge. AB - The objective of this study was to investigate the recovery potential of molybdenum (Mo), nickel (Ni) and cobalt (Co) from synthetic and real acidic leachate of a mineral sludge from a metal recycling plant by sulfide precipitation. The operational parameters (metal sulfide (M/S) ratio 0.1-1, agitation speed 0-100 rpm, contact time 15-120 min and pH 1-5) were optimized in batch conditions on synthetic metal leachate (0.5 M HNO3, Mo = 101.6 mg L(-1), Ni = 70.8 mg L(-1), Co = 27.1 mg L(-1)) with a 0.1 M Na2S solution. Additionally, recovery of the target metals was theoretically simulated with a chemical equilibrium model (Visual MINTEQ 3.0). The optimized Na2S precipitation of metals from the synthetic leachate resulted in the potential selective recovery of Mo at pH 1 (98% by modeling, 95% experimental), after simultaneous precipitation of Ni and Co as sulfide at pH 4 (100% by modeling, 98% experimental). Metal precipitation from the real leachate (18 M H2SO4, Mo = 10,160 mg L(-1), Ni = 7,080 mg L(-1), Co = 2,710 mg L(-1)) was performed with 1 M Na2S, and resulted in a maximal Mo recovery at pH 2 (50%), while maximal recoveries of Ni and Co were observed at pH 4 (56% and 60%, respectively). Real leachate gave a lower metals recovery efficiency compared with synthetic leachate, which can be attributed to changes in the pH, nature of leachant, co-precipitation of Zn and competition for S(2-) ions. PMID- 26824138 TI - Germinating Peanut (Arachis hypogaea L.) Seedlings Attenuated Selenite-Induced Toxicity by Activating the Antioxidant Enzymes and Mediating the Ascorbate Glutathione Cycle. AB - Selenite can enhance the selenium nutrition level of crops, but excessive selenite may be toxic to plant growth. To elucidate the mechanisms underlying the role of selenite in production and detoxification of oxidative toxicity, peanut seedlings were developed with sodium selenite (0, 3, and 6 mg/L). The effects of selenite on antioxidant capacity, transcript levels of antioxidant enzyme genes, and enzyme activities in hypocotyl were investigated. The CuZn-SOD, GSH-Px, GST, and APX gene expression levels and their enzyme activities in selenite treatments were 1.0-3.6-fold of the control. Selenite also significantly increased the glutathione and ascorbate concentrations by mediating the ascorbate-glutathione cycle, and the selenite-induced hydrogen peroxide may act as a second messenger in the signaling pathways. This work has revealed a complex antioxidative response to selenite in peanut seedling. Understanding these mechanisms may help future research in increasing selenite tolerance and selenium accumulation in peanut and other crops. PMID- 26824139 TI - Mechanisms of the Antimicrobial Activities of Graphene Materials. AB - A thorough understanding of the antimicrobial mechanisms of graphene materials (GMs) is critical to the manipulation of highly efficient antimicrobial nanomaterials for future biomedical applications. Here we review the most recent studies of GM-mediated antimicrobial properties. This review covers the physicochemical properties of GMs, experimental surroundings, and selected microorganisms as well as the interaction between GMs and selected microorganisms to explore controversial antimicrobial activities. Finally, we rationally analyze the strengths and weaknesses of the proposed mechanisms and provide new insights into the remaining challenges and perspectives for future studies. PMID- 26824140 TI - Entangled Electrons Foil Synthesis of Elusive Low-Valent Vanadium Oxo Complex. AB - We examine the recently reported first synthesis of the elusive low-valent vanadium(III) in a vanadium oxo complex with a computation representing 10(21) quantum degrees of freedom. While this computation is intractable with a conventionally constructed wave function, it is performed here by a direct calculation of the system's two-electron reduced density matrix (2-RDM), where the 2-RDM is constrained by nontrivial conditions, known as N-representability conditions, that restrict the 2-RDM to represent an N electron quantum system. We show that the added (reducing) electron becomes entangled among the five pyridine ligands. While smaller calculations predict a metal-centered addition, large scale 2-RDM calculations show that quantum entanglement redirects the electron transfer to the pyridine ligands, resulting in a ligand-centered addition. Beyond its implications for the synthesis of low-valent vanadium oxo complexes, the result suggests new possibilities for using quantum entanglement to predict and control electron transfer in chemical and biological materials. PMID- 26824141 TI - Combining Ferric Salt and Cactus Mucilage for Arsenic Removal from Water. AB - New methods to remediate arsenic-contaminated water continue to be studied, particularly to fill the need for accessible methods that can significantly impact developing communities. A combination of cactus mucilage and ferric (Fe(III)) salt was investigated as a flocculation-coagulation system to remove arsenic (As) from water. As(V) solutions, ferric nitrate, and mucilage suspensions were mixed and left to stand for various periods of time. Visual and SEM observations confirmed the flocculation action of the mucilage as visible flocs formed and settled to the bottom of the tubes within 3 min. The colloidal suspensions without mucilage were stable for up to 1 week. Sample aliquots were tested for dissolved and total arsenic by ICP-MS and HGAFS. Mucilage treatment improved As removal (over Fe(III)-only treatment); the system removed 75-96% As in 30 min. At neutral pH, removal was dependent on Fe(III) and mucilage concentration and the age of the Fe(III) solution. The process is fast, achieving maximum removal in 30 min, with the majority of As removed in 10-15 min. Standard jar tests with 1000 MUg/L As(III) showed that arsenic removal and settling rates were pH-dependent; As removal was between 52% (high pH) and 66% (low pH). PMID- 26824143 TI - A Polysulfide-Trapping Interface for Electrochemically Stable Sulfur Cathode Development. AB - Lithium-sulfur (Li-S) cells have a strong edge to become an inexpensive, high capacity rechargeable battery system. However, currently, several prohibitive challenges occur within the sulfur core, especially the polysulfide-diffusion problem. To address these scientific issues, we present here a boron-doped multiwalled carbon nanotube coated separator (B-CNT-coated separator). The B-CNT coated separator creates a polysulfide trap between the pure sulfur cathode and the polymeric separator as a "polysulfide-trapping interface," stabilizing the active material and allowing the dissolved polysulfides to activate the bulk sulfur cores. Therefore, the dissolved polysulfides change from causing fast capacity fade to assisting with the activation of bulk sulfur clusters in pure sulfur cathodes. Moreover, the heteroatom-doped polysulfide-trapping interface is currently one of the missing pieces of carbon-coated separators, which might inspire further studies in its effect and battery chemistry. Li-S cells employing B-CNT-coated separators (i) exhibit improved cyclability at various cycling rates from 0.2C to 1.0C rate and (ii) attain a high capacity retention rate of 60% with a low capacity fade rate of 0.04% cycle(-1) after 500 cycles. We believe that our B-CNT-coated separator could light up a new research area for integrating heteroatom-doped carbon into the flexible, lightweight, carbon-coated separator. PMID- 26824142 TI - Development of a Self-Assembled Nanoparticle Formulation of Orlistat, Nano-ORL, with Increased Cytotoxicity against Human Tumor Cell Lines. AB - Fatty acid synthase (FASN), the enzyme that catalyzes de novo synthesis of fatty acids, is expressed in many cancer types. Its potential as a therapeutic target is well recognized, but inhibitors of FASN have not yet been approved for cancer therapy. Orlistat (ORL), an FDA-approved lipase inhibitor, is also an effective inhibitor of FASN. However, ORL is extremely hydrophobic and has low systemic uptake after oral administration. Thus, new strategies are required to formulate ORL for cancer treatment as a FASN inhibitor. Here, we report the development of a nanoparticle (NP) formulation of ORL using amphiphilic bioconjugates that are derived from hyaluronic acid (HA), termed Nano-ORL. The NPs were loaded with up to 20 wt % weight of ORL at greater than 95% efficiency. The direct inhibition of the human recombinant thioesterase domain of FASN by ORL extracted from Nano-ORL was similar to that of stock ORL. Nano-ORL demonstrated a similar ability to inhibit cellular FASN activity when compared to free ORL, as demonstrated by analysis of (14)C-acetate incorporation into lipids. Nano-ORL treatment also disrupted mitochondrial function similarly to ORL by reducing adenosine triphosphate turnover in MDA-MB-231 and LNCaP cells. Nano-ORL demonstrated increased potency compared to ORL toward prostate and breast cancer cells. Nano ORL decreased viability of human prostate and breast cancer cell lines to 55 and 57%, respectively, while free ORL decreased viability to 71 and 79% in the same cell lines. Moreover, Nano-ORL retained cytotoxic activity after a 24 h preincubation in aqueous conditions. Preincubation of ORL dramatically reduced the efficacy of ORL as indicated by high cell viability (>85%) in both breast and prostate cell lines. These data demonstrate that NP formulation of ORL using HA derived polymers retains similar levels of FASN, lipid synthesis, and ATP turnover inhibition while significantly improving the cytotoxic activity against cancer cell lines. PMID- 26824144 TI - Oral Bioavailability, Bioaccessibility, and Dermal Absorption of PAHs from Soil State of the Science. AB - This article reviews the state of the science regarding oral bioavailability, bioaccessibility, and dermal absorption of carcinogenic polycyclic aromatic hydrocarbons (cPAHs) in soil by humans, and discusses how chemical interactions may control the extent of absorption. Derived from natural and anthropomorphic origins, PAHs occur in a limited number of solid and fluid matrices (i.e., PAH sources) with defined physical characteristics and PAH compositions. Existing studies provide a strong basis for establishing that oral bioavailability of cPAHs from soil is less than from diet, and an assumption of 100% relative bioavailability likely overestimates exposure to cPAHs upon ingestion of PAH contaminated soil. For both the oral bioavailability and dermal absorption studies, the aggregate data do not provide a broad understanding of how different PAH source materials, PAH concentrations, or soil chemistries influence the absorption of cPAHs from soil. This article summarizes the existing studies, identifies data gaps, and provides recommendations for the direction of future research to support new default or site-specific bioavailability adjustments for use in human health risk assessment. PMID- 26824146 TI - Fluid stimulation elicits hearing in the absence of air and bone conduction--An animal study. AB - Conclusion Cochlea can be directly excited by fluid (soft-tissue) stimulation. Objective To determine whether there is no difference in auditory-nerve-brainstem evoked response (ABR) thresholds to fluid stimulation between normal and animal models of post radical-mastoidectomy, as seen in a previous human study. Background It has been shown in humans that hearing can be elicited with stimulation to fluid in the external auditory meatus (EAM), and radical mastoidectomy cavity. These groups differed in age, initial hearing, and drilling exposure. To overcome this difference, experiments were conducted in sand-rats, first intact, and after inducing a radical-mastoidectomy. Methods The EAM of five sand-rats was filled with 0.3 ml saline. ABR thresholds were determined in response to vibratory stimulation by a clinical bone-vibrator with a plastic rod, applied to the saline in the EAM. Then the tympanic membrane was removed, and malleus dislocated (radical-mastoidectomy model). The cavity was filled with 0.45 ml saline and the ABR threshold was determined in response to vibratory stimulation to the cavity fluid. Results There was no difference in ABR fluid thresholds to EAM and mastoidectomy cavity stimulation. Air-conduction stimulation from the bone-vibrator was not involved (conductive loss due to fluid). Bone-conduction stimulation was not involved (large difference in acoustic impedance between fluid and bone). PMID- 26824145 TI - Parameterization of a disease progression simulation model for sequentially treated metastatic human epidermal growth factor receptor 2 positive breast cancer patients. AB - Background The objective of this study is twofold: 1) to propose a simulation model for HER2+ metastatic breast cancer (mBC) which could further be used to assess the overall cost-effectiveness of the treatment sequences that would maximize survival of patients, and 2) to estimate transitional probabilities between treatment lines required to parameterize the simulation model, in the absence of individual patient data (IPD). Methods Individual patient data (IPD) were reconstructed for treatment lines composing four treatment sequences. Parametric models were tested to select the model that best fits the IPD. The transitional probability equations, used for disease progression modeling, were obtained by substituting the parameters of the general equation for transitional probabilities by the parameters estimated from fitted distributions. Results The log-logistic model best fitted the reconstructed data for progression-free and overall survival curves for each line of treatment. The shapes and scales of the log-logistic models were used to develop the transitional probability equations for the HER2+ mBC simulation model. KEY LIMITATIONS: The estimation of the transitional probabilities depends heavily on the accuracy of the IPD reconstruction. Nonetheless, analytical and graphical tests can be performed to check the face validity of the reconstructed data. Additionally, sensitivity analyses can be conducted to test the impact of uncertainty surrounding the estimated parameters defining equations for transitional probabilities. Conclusion The results of this study can be used as input in model-based economic evaluations of sequential therapy for HER2+ mBC. PMID- 26824147 TI - Beyond Dispersity: Deterministic Control of Polymer Molecular Weight Distribution. AB - The breadth of the molecular weight distributions (MWD) of polymers influences their physical properties; however, no synthetic methods allow precise control of the exact shape and composition of a distribution. We report a modular strategy that enables deterministic control over polymer MWD through temporal regulation of initiation in nitroxide-mediated polymerization reactions. This approach is applicable to any controlled polymerization that uses a discrete initiator, and it allows the use of MWD composition as a parameter to tune material properties. PMID- 26824148 TI - Innovative Strategies Designed to Improve Adult Pneumococcal Immunizations in Safety Net Patient-Centered Medical Homes. AB - Streptococcus pneumoniae is a principal cause of serious illness, including bacteremia, meningitis, and pneumonia, worldwide. Pneumococcal immunization is proven to reduce morbidity and mortality in high-risk adult and elderly populations. Current pneumococcal vaccination practices are suboptimal in part because of recommendation complexity, the high cost of provider-driven immunization interventions, and outreach methods that are not patient-centric. These barriers are amplified within the safety net. This paper identifies efforts by the Los Angeles County Department of Health Services to increase pneumococcal immunization rates for adult indigent patient populations. A 4-part approach will be used to increase vaccination rates: (1) protocol driven care, (2) staff education, (3) electronic identification of eligible patients, and (4) automated patient outreach and scheduling. The proposed analytics plan and potential for scalability are described. (Population Health Management 2016;19:240-247). PMID- 26824149 TI - Effective Interpersonal Communication: A Practical Guide to Improve Your Life. AB - Use of effective interpersonal communication strategies by nurses in both personal and professional settings, may reduce stress, promote wellness, and therefore, improve overall quality of life. This article briefly explores the concept of interpersonal communication as it relates to Maslow's hierarchy of human needs; describes personal variables and the interaction of internal and external variables that can impact communication; and discusses possible causes and consequences of ineffective communication. Drawing on both the literature and experiences as a longtime provider of care in the mental health field, the author offers multiple practical strategies, with specific examples of possible responses for effective communication. Recommendations in this article are intended for nurses to consider as they seek healthy communication strategies that may be useful in both their personal and professional lives. PMID- 26824150 TI - Social Media and Nurses: Insights for Promoting Health for Individual and Professional Use. AB - Social media use can have a significant impact on the health of nurses, both at the individual level and in the workplace. There are positive and negative consequences of social media use for nurses, including potential health consequences. This article provides a brief overview of social media and then explores nursing health and social media and risks for nurses. Social media use also extends to healthcare organizations; with implications for consumers of healthcare delivery. A variety of emerging best practices can guide social media use for nurses. The authors also discuss suggestions for using social media carefully, and future directions for research. PMID- 26824151 TI - Practicing Self-Care for Nurses: A Nursing Program Initiative. AB - Self-care is imperative to personal health, sustenance to continue to care for others, and professional growth. This article briefly reviews stressors common to students and nurses and the importance of practicing self-care to combat stress and promote health in practice. Florida Atlantic University offers a course for all levels of undergraduate nursing students called Caring for Self. The course, supported by principles of Adult Learning Theory, focuses on guiding the nurse to practice and model self-care. The author describes the evolution of this self care initiative by discussing the needs assessment, course description and strategies, examples of course activities, and an exemplar of student impact. The conclusion offers discussion of challenges and lessons noted by faculty and students. PMID- 26824152 TI - Implementation of a Participant-Centered Weight Management Program for Older Nurses: A Feasibility Study. AB - American nurses (3.06 million) are at high risk for being overweight, as the majority are post-menopausal women (93.3% female; mean age 47). Studies have indicated that more than half of all nurses are either overweight or obese. This fact is of concern because nurses often lead major health promotion efforts. The aim of this study was to examine the feasibility of a novel participant-centered weight management program (PCWM) among nurses. The participant-centered (P-C) theoretical framework used originated from the field of usability engineering (i.e., user-centered design). Study methods included a single group pre-test/post test design (baseline, eight weeks, three months) and an intervention consisting of face-to-face education sessions, technology-augmented exercise programs, and an eHealth portal. The results demonstrated a significant decrease in body weight, increased fruit and vegetable consumption, and increased exercise at eight weeks. In our discussion of this study, we note that although the intervention effects decreased at three months, these results are promising, considering that the intervention used was not regimented and relied only on nurses' activation of their planned health behaviors. The major limitation of the study was the small sample size recruited from one large community hospital. Further research is needed to improve the sustainability of the program. PMID- 26824153 TI - Factors Related to Healthy Diet and Physical Activity in Hospital-Based Clinical Nurses. AB - Hospitals often promote healthy lifestyles, but little is known about nurses' actual diet and physical activity. Greater understanding about these lifestyle choices for clinical nurses may improve existing hospital-based programs and/or create desirable services. This article discusses a study that considered diet and physical activity of clinical nurses, using elements of Pender's self-care theory as a conceptual framework. Study methods included a cross-sectional, correlational design and a convenience sample of 278 nurses who worked on units with 24 hours/day and seven days-per-week responsibilities. Participants completed diet and exercise questionnaires about perceptions of attitudes and opinions, barriers, diet benefits/exercise motivators, self-efficacy, and locus of control, and personal and work characteristics. Diet and activity categories were created. Study results demonstrated that over 50% of nurses had moderately healthy diets but were insufficiently active. Healthy diet and physical activity levels were associated with higher self-efficacy, more diet benefits and physical activity motivators, fewer perceived barriers, and confidence in body image. The article discussion and conclusion sections note areas for future research and suggest that focused interventions that address benefits, motivators, and self efficacy may increase participation in hospital-based programs and enhance healthy lifestyle for hospital-based clinical nurses. PMID- 26824154 TI - Designing Exercise and Nutrition Programs to Promote Normal Weight Maintenance for Nurses. AB - Living a healthy lifestyle is a constant choice. As a life goal, it is a decision to uphold every moment and is best achieved with support of others. There are a multitude of workplace wellness and healthy lifestyle programs that address achieving and maintaining the goal of normal weight over a lifetime. Fewer such evidence based programs exist and a goal of our hospital is to create a comprehensive wellness program based on evidence. In the context of normal weight maintenance in nurses, this article discusses selected challenges for healthy eating and exercise and nurse fitness programs based on the author and her colleagues experiences with specific obesity research interventions, such as Nurses Living FitTM, that we designed and offered. An exemplar provides details about our wellness programs, which included three annual walk or run events, one full day conference, and a series of multiple exercise, yoga, and nutrition sessions. Our goal was to expose nurses to healthier lifestyle aspects with a primary focus on the optimal balance of exercise and nutrition. Over the years of research, events, and programs, greater than 1,000 people have participated. The conclusion includes implications for education and practice in the hope that our experiences may motive nurses to design exercise and nutrition programs to promote normal weight maintenance in nurses. PMID- 26824155 TI - Healthy Eating for Healthy Nurses: Nutrition Basics to Promote Health for Nurses and Patients. AB - Nurses care for people each day in many settings such as hospitals, physician offices, schools, and public health facilities. Such positions often require nurses to work variable and long hours, exposing them to the stressors of caring for people who are ill. These stressors can support poor food choices that adversely affect the health and well-being of the nurse. Nurses are also an integral part of providing nutrition related information to patients. As such, patients may be very cognizant of the health habits of their nurses. Eating for good health is one way that nurses can reduce the impact of stressors on the body and positively influence their health, allowing them to better care for patients and themselves. This article reviews two common nutrition related areas of concern to nurses, stressors, inflammation, and nutrition and sleep and eating patterns, that can lead to obesity. Knowledge and attitudes about nutrition education are also discussed briefly. Finally, the article offers a review of nutrition basics for nurses and suggestions to avoid potential food pitfalls common for nurses. PMID- 26824156 TI - The Value of Library and Information Services in Nursing and Patient Care. AB - Libraries are a primary resource for evidence-based practice. This study, using a critical incident survey administered to 6,788 nurses at 118 hospitals, sought to explore the influence of nurses' use of library resources on both nursing and patient outcomes. In this article, the authors describe the background events motivating this study, the survey methods used, and the study results. They also discuss their findings, noting that use of library resources showed consistently positive relationships with changing advice given to patients, handling patient care differently, avoiding adverse events, and saving time. The authors discuss the study limitations and conclude that the availability and use of library and information resources and services had a positive impact on nursing and patient outcomes, and that nurse managers play an important role both by encouraging nurses to use evidence-based library resources and services and by supporting the availability of these resources in healthcare settings. PMID- 26824157 TI - Graduate Clinical Nurse Preceptors: Implications for Improved Intra-Professional Collaboration. AB - Advanced practice nurses have increased in number and public acceptance. Students preparing for these roles require quality clinical education so they are prepared to assume collaborative roles in healthcare settings. Although graduate clinical preceptors have a vitally important role in the clinical education and professional socialization of advanced practice students, there is a paucity of evidence about factors that influence their role commitment. In this article, the authors review the literature related to graduate-level, clinical-preceptor experiences; describe their study of 91 graduate clinical preceptors that identified factors influencing graduate clinical preceptors' role commitment; report and discuss their findings; as well as the limitations of this study. They conclude that the graduate clinical preceptor role needs to be more visible and better integrated into schools of nursing and healthcare organizational structures, and identify the need for intra-professional collaboration among nursing faculty, administrators, and clinicians to facilitate the recruitment, cultivation, and retention of graduate clinical preceptors. PMID- 26824158 TI - Legislative: Responding to the Fatal Opioid Overdose Epidemic: A Call to Nurses. PMID- 26824159 TI - Cochrane Review Brief: Nurse Versus Physician-Led Care for the Management of Asthma. PMID- 26824160 TI - Cochrane Review Brief: Exit Interviews to Reduce Turnover Amongst Healthcare Professionals. PMID- 26824161 TI - Informatics: International Classification of Diseases-10: Implications for Nursing. PMID- 26824162 TI - Cochrane Review Brief: Ergonomic design and training for preventing work-related musculoskeletal disorders of the upper limb and neck in adults. PMID- 26824163 TI - Cochrane Review Brief: Chinese Herbal Medicine for Endometriosis. PMID- 26824164 TI - Probing Effective Hamiltonian Operators by Single-Crystal EPR: A Case Study Using Dinuclear Cr(III) Complexes. AB - The use of a simple two-center model to describe exchange-coupled systems of various complexities is common in the field of coordination chemistry and molecular magnetism. In this work we investigate the applicability of this model experimentally, employing multifrequency, single-crystal EPR on axial dinuclear chromium(III) systems amenable to accurate parametrizations. The very high confidence with which zero-field splitting parameters can be determined by this technique, applied to the systems in question, allows for an in-depth analysis of the modeling. We experimentally demonstrate and qualitatively account for the energy-dependent modification of the spin-multiplet anisotropies, which is introduced by the exchange interaction. Even for the simple systems under consideration, we find that the standard modeling provides an inadequate parametrization of experimental data, and we present a convenient model extension, which improves the description. PMID- 26824165 TI - Epigenetics: Novel Therapeutics Targeting Epigenetics. PMID- 26824166 TI - Sheet Size-Induced Evaporation Behaviors of Inkjet-Printed Graphene Oxide for Printed Electronics. AB - The size of chemically modified graphene nanosheets is a critical parameter that affects their performance and applications. Here, we show that the lateral size of graphene oxide (GO) nanosheets is strongly correlated with the concentration of graphite oxide present in the suspension as graphite oxide is exfoliated by sonication. The size of the GO nanosheets increased from less than 100 nm to several micrometers as the concentration of graphite oxide in the suspension was increased up to a critical concentration. An investigation of the evaporation behavior of the GO nanosheet solution using inkjet printing revealed that the critical temperature of formation of a uniform film, T(c), was lower for the large GO nanosheets than for the small GO nanosheets. This difference was attributed to the interactions between the two-dimensional structures of GO nanosheets and the substrate as well as the interactions among the GO nanosheets. Furthermore, we fabricated organic thin film transistors (OTFTs) using line patterned reduced GO as electrodes. The OTFTs displayed different electrical performances, depending on the graphene sheet size. We believe that our new strategy to control the size of GO nanosheets and our findings about the colloidal and electrical properties of size-controlled GO nanosheets will be very effective to fabricate graphene based printed electronics. PMID- 26824167 TI - The Noncentral Chi-square Distribution in Misspecified Structural Equation Models: Finite Sample Results from a Monte Carlo Simulation. AB - The noncentral chi-square distribution plays a key role in structural equation modeling (SEM). The likelihood ratio test statistic that accompanies virtually all SEMs asymptotically follows a noncentral chi-square under certain assumptions relating to misspecification and multivariate distribution. Many scholars use the noncentral chi-square distribution in the construction of fit indices, such as Steiger and Lind's (1980) Root Mean Square Error of Approximation (RMSEA) or the family of baseline fit indices (e.g., RNI, CFI), and for the computation of statistical power for model hypothesis testing. Despite this wide use, surprisingly little is known about the extent to which the test statistic follows a noncentral chi-square in applied research. Our study examines several hypotheses about the suitability of the noncentral chi-square distribution for the usual SEM test statistic under conditions commonly encountered in practice. We designed Monte Carlo computer simulation experiments to empirically test these research hypotheses. Our experimental conditions included seven sample sizes ranging from 50 to 1000, and three distinct model types, each with five specifications ranging from a correct model to the severely misspecified uncorrelated baseline model. In general, we found that for models with small to moderate misspecification, the noncentral chi-square distribution is well approximated when the sample size is large (e.g., greater than 200), but there was evidence of bias in both mean and variance in smaller samples. A key finding was that the test statistics for the uncorrelated variable baseline model did not follow the noncentral chi-square distribution for any model type across any sample size. We discuss the implications of our findings for the SEM fit indices and power estimation procedures that are based on the noncentral chi-square distribution as well as potential directions for future research. PMID- 26824168 TI - Sample Size Requirements for Accurate Estimation of Squared Semi-Partial Correlation Coefficients. AB - The increase in the squared multiple correlation coefficient associated with a variable in a regression equation is a commonly used measure of importance in regression analysis. An alternative measure of importance is the difference in the adjusted squared multiple correlation coefficients. Both estimate the difference in the population squared multiple correlation coefficients (Deltarho(2)), a quantity also called a squared semi-partial correlation coefficient. In planning a study that will use regression analysis, it is important to select a sample size that will allow Deltarho(2) to be estimated with adequate accuracy. Results showed that the sample size necessary for adequate accuracy depend strongly on three factors: (a) the population squared multiple correlation coefficient (rho(2)), (b) the population increase in rho(2), and (c) the desired degree of accuracy. The number of predictors had a small effect on the required sample size. Tables to facilitate sample size selection were presented. PMID- 26824169 TI - Analysis of Multitrait-Multioccasion Data: Additive versus Multiplicative Models. AB - The aim of this article is to address the question of whether empirical multitraitmultioccasion data conform more closely to multiplicative models than to additive models. Four additive models and two versions of the multiplicative Direct Product (DP) model (Browne, 1984) are tested. A set of 21 multitrait multioccasion matrices is analyzed by means of LISREL 8 (Joreskog & Sorbom, 1993). The results obtained across different models are evaluated according to plausibility of solutions and goodness-of-fit. The different good-fitting models are compared in terms of goodness-of-fit and in terms of the conclusions about construct validity derived from the models. Results show that both additive and multiplicative models (specifically the additive Correlated Trait-Correlated Uniqueness model and the multiplicative Composite Direct Product model) usually fit the same MTMO data. Moreover both kinds of models are frequently equivalent in terms of goodness-of-fit. Finally, although general conclusions about construct validity are similar across models, the results obtained suggest that the conclusions about the relevance of each trait and occasion derived from additive and multiplicative models can differ substantially depending on the number of traits and occasions. PMID- 26824170 TI - Analytic Estimation of Standard Error and Confidence Interval for Scale Reliability. AB - An analytic approach to standard error and confidence interval estimation of scale reliability with fixed congeneric measures is proposed that is based on a generally applicable estimator stability evaluation procedure, the delta method (e.g., Ogasawara, 1999). The approach complements wide-spread point estimation of composite reliability in behavioral scale construction and development, and can be used to evaluate precision of estimates and plausible ranges for reliability of multiple-component instruments in studied populations. The method is illustrated by means of a numerical example. PMID- 26824171 TI - Do Reactions to Tests Produce Changes in the Construct Measured? AB - Applicants for state trooper positions completed two tests and three measures of test reactions as part of a study that examined their reactions to different types of measures and the impact these reactions had on the construct measured by the test. African American examinees felt a video-based measure that involved their interpretation of job-related incidents was more face valid than a reading comprehension measure based on job-related material though their perceptions of the two tests' fairness and predictive validity were similar. Caucasian examinees reacted less favorably to the video-based measure. Results also indicate that test reactions and race are related minimally to both video and reading comprehension testlets beyond their relationship to the latent factor underlying the measure. The latter finding is taken as evidence that test reactions did not affect the nature of the underlying factor measured by a test in this situation. PMID- 26824172 TI - A Method for Modeling the Intrinsic Dynamics of Intraindividual Variability: Recovering the Parameters of Simulated Oscillators in Multi-Wave Panel Data. AB - A simple method for fitting differential equations to multi-wave panel data performs remarkably well in recovering parameters from underlying continuous models with as few as three waves of data. Two techniques for fitting models of intrinsic dynamics to intraindividual variability data are examined by testing these techniques' behavior in recovering the parameters from data generated by two simulated systems of differential equations. Each simulated data set contains 100 "subjects" each of whom are measured at only three points in time. A local linear approximation of the first and second derivatives of the subject's data accurately recovers the true parameters of each simulation. A statespace embedding technique for estimating the first and second derivatives does not recover the parameters as well. An optimum sampling interval can be estimated for this model as that interval at which multiple R(2) first nears its asymptotic value. PMID- 26824173 TI - Recognition of MBR Reviewers. PMID- 26824174 TI - Spiroindolone NITD609 is a novel antimalarial drug that targets the P-type ATPase PfATP4. AB - Malaria is caused by the Plasmodium parasite and is a major health problem leading to many deaths worldwide. Lack of a vaccine and increasing drug resistance highlights the need for new antimalarial drugs with novel targets. Antiplasmodial activity of spiroindolones was discovered through whole-cell, phenotypic screening methods. Optimization of the lead spiroindolone improved both potency and pharmacokinetic properties leading to drug candidate NITD609 which has produced encouraging results in clinical trials. Spiroindolones inhibit PfATP4, a P-type Na(+)-ATPase in the plasma membrane of the parasite, causing a fatal disruption of its sodium homeostasis. Other diverse compounds from the Malaria Box appear to target PfATP4 warranting further research into its structure and binding with NITD609 and other potential antimalarial drugs. PMID- 26824175 TI - Managing Migraine Headaches in Children and Adolescents. AB - The diagnosis and management of migraine headaches can be challenging in children and adolescents. The description of migraine in this population may include symptoms that are not typically described in adults. Treatment options for pediatric migraine is increasing, however remain limited. This article will go through the key components to diagnosing migraine in pediatric patients as well as give options for short and long-term management. PMID- 26824176 TI - Ecological succession reveals potential signatures of marine-terrestrial transition in salt marsh fungal communities. AB - Marine-to-terrestrial transition represents one of the most fundamental shifts in microbial life. Understanding the distribution and drivers of soil microbial communities across coastal ecosystems is critical given the roles of microbes in soil biogeochemistry and their multifaceted influence on landscape succession. Here, we studied the fungal community dynamics in a well-established salt marsh chronosequence that spans over a century of ecosystem development. We focussed on providing high-resolution assessments of community composition, diversity and ecophysiological shifts that yielded patterns of ecological succession through soil formation. Notably, despite containing 10- to 100-fold lower fungal internal transcribed spacer abundances, early-successional sites revealed fungal richnesses comparable to those of more mature soils. These newly formed sites also exhibited significant temporal variations in beta-diversity that may be attributed to the highly dynamic nature of the system imposed by the tidal regime. The fungal community compositions and ecophysiological assignments changed substantially along the successional gradient, revealing a clear signature of ecological replacement and gradually transforming the environment from a marine into a terrestrial system. Moreover, distance-based linear modelling revealed soil physical structure and organic matter to be the best predictors of the shifts in fungal beta-diversity along the chronosequence. Taken together, our study lays the basis for a better understanding of the spatiotemporally determined fungal community dynamics in salt marshes and highlights their ecophysiological traits and adaptation in an evolving ecosystem. PMID- 26824177 TI - Genomic reconstruction of a novel, deeply branched sediment archaeal phylum with pathways for acetogenesis and sulfur reduction. AB - Marine and estuary sediments contain a variety of uncultured archaea whose metabolic and ecological roles are unknown. De novo assembly and binning of high throughput metagenomic sequences from the sulfate-methane transition zone in estuary sediments resulted in the reconstruction of three partial to near complete (2.4-3.9 Mb) genomes belonging to a previously unrecognized archaeal group. Phylogenetic analyses of ribosomal RNA genes and ribosomal proteins revealed that this group is distinct from any previously characterized archaea. For this group, found in the White Oak River estuary, and previously registered in sedimentary samples, we propose the name 'Thorarchaeota'. The Thorarchaeota appear to be capable of acetate production from the degradation of proteins. Interestingly, they also have elemental sulfur and thiosulfate reduction genes suggesting they have an important role in intermediate sulfur cycling. The reconstruction of these genomes from a deeply branched, widespread group expands our understanding of sediment biogeochemistry and the evolutionary history of Archaea. PMID- 26824178 TI - Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Development of a CFD Model. AB - PURPOSE: The objective of this study was to develop a computational fluid dynamics (CFD) model to predict the deposition, dissolution, clearance, and absorption of pharmaceutical particles in the human nasal cavity. METHODS: A three-dimensional nasal cavity geometry was converted to a surface-based model, providing an anatomically-accurate domain for the simulations. Particle deposition data from a commercial nasal spray product was mapped onto the surface model, and a mucus velocity field was calculated and validated with in vivo nasal clearance rates. A submodel for the dissolution of deposited particles was developed and validated based on comparisons to existing in vitro data for multiple pharmaceutical products. A parametric study was then performed to assess sensitivity of epithelial drug uptake to model conditions and assumptions. RESULTS: The particle displacement distance (depth) in the mucus layer had a modest effect on overall drug absorption, while the mucociliary clearance rate was found to be primarily responsible for drug uptake over the timescale of nasal clearance for the corticosteroid mometasone furoate (MF). The model revealed that drug deposition in the nasal vestibule (NV) could slowly be transported into the main passage (MP) and then absorbed through connection of the liquid layer in the NV and MP regions. As a result, high intersubject variability in cumulative uptake was predicted, depending on the length of time the NV dose was left undisturbed without blowing or wiping the nose. CONCLUSIONS: This study has developed, for the first time, a complete CFD model of nasal aerosol delivery from the point of spray formation through absorption at the respiratory epithelial surface. For the development and assessment of nasal aerosol products, this CFD-based in silico model provides a new option to complement existing in vitro nasal cast studies of deposition and in vivo imaging experiments of clearance. PMID- 26824179 TI - Developing professional values: perceptions of francophone occupational therapists in Quebec, Canada. AB - Objective Recent literature shows growing interest in the values displayed by occupational therapists. Yet, none of these writings has so far examined the factors that contribute to the development of occupational therapists' professional values. These factors are important, since values play a pivotal role in forging professional identity, which in the case of some occupational therapists remains somewhat ambiguous. This article proposes possible answers to the following question: What do Quebec Francophone occupational therapists perceive as the building blocks of their professional values? Methods Using a phenomenological qualitative method, the subjective experience of occupational therapists in Quebec, Canada was examined. Twenty-six occupational therapists took part in the study. Results As intended, their professional experience was varied. According to the participants, four factors contributed significantly to their professional values: professional experience, university training, personal experience, and professional development. However, fewer than 50% of the participants cited six other factors (workplace, family upbringing, personal development, personality and abilities, professional normative framework, and sociocultural background). Conclusions Most of these results are consistent with those documented in existing works. They point to the relevance of discussing professional values during university training and continuing professional development, as well as encouraging occupational therapists to become exemplars for their colleagues and interns. This study constitutes an initial step in understanding how occupational therapists' axiological identity is formed. PMID- 26824180 TI - Suppression of scarring in peripheral nerve implants by drug elution. AB - OBJECTIVE: Medical implants made of non-biological materials provoke a chronic inflammatory response, resulting in the deposition of a collagenous scar tissue (ST) layer on their surface, that gradually thickens over time. This is a critical problem for neural interfaces. Scar build-up on electrodes results in a progressive decline in signal level because the scar tissue gradually separates axons away from the recording contacts. In regenerative sieves and microchannel electrodes, progressive scar deposition will constrict and may eventually choke off the sieve hole or channel lumen. Interface designs need to address this issue if they are to be fit for long term use. This study examines a novel method of inhibiting the formation and thickening of the fibrous scar. APPROACH: Research to date has mainly focused on methods of preventing stimulation of the foreign body response by implant surface modification. In this paper a pharmacological approach using drug elution to suppress chronic inflammation is introduced. Microchannel implants made of silicone doped with the steroid drug dexamethasone were implanted in the rat sciatic nerve for periods of up to a year. Tissue from within the microchannels was compared to that from control devices that did not release any drug. MAIN RESULTS: In the drug eluting implants the scar layer was significantly thinner at all timepoints, and unlike the controls it did not continue to thicken after 6 months. Control implants supported axon regeneration well initially, but axon counts fell rapidly at later timepoints as scar thickened. Axon counts in drug eluting devices were initially much lower, but increased rather than declined and by one year were significantly higher than in controls. SIGNIFICANCE: Drug elution offers a potential long term solution to the problem of performance degradation due to scarring around neural implants. PMID- 26824181 TI - A SNP in pri-miR-10a is associated with recurrent spontaneous abortion in a Han Chinese population. AB - MicroRNA-10a (miR-10a) has a wide range of functions in nearly all mammalian tissues and is involved in the occurrence of many diseases. However, it remains unknown whether miR-10a is associated with human recurrent spontaneous abortion (RSA). In this study, we found that rs3809783 A > T in miR-10a coding region was significantly associated with the increase of the risk of human unexplained RSA (URSA) acquisition in a Han-Chinese population. The T allele of rs3809783 hindered the production of mature miR-10a. A to T substitution in miR-10a rs3809783 repressed cell proliferation and migratory capacity. Further investigation discovered that Bcl-2-interacting mediator (Bim) was the functional target of miR-10a and inversely regulated Bim expression. Dual-luciferase assay indicated that A allele in miR-10a rs3809783 could more effectively suppress Bim expression than T allele. In addition, A to T substitution in miR-10a rs3809783 attenuated the sensibility of cells to progesterone and its antagonist mifepristone. Collectively, our data suggest that rs3809783 A > T in pri-miR-10a may be conductive to the genetic predisposition to RSA by disrupting the production of mature miR-10a and reinforcing the expression of Bim. PMID- 26824182 TI - MiR-129 triggers autophagic flux by regulating a novel Notch-1/ E2F7/Beclin-1 axis to impair the viability of human malignant glioma cells. AB - Abnormalities of autophagy have been implicated in an increasing number of human cancers, including glioma. To date, there is a wealth of evidence indicating that microRNAs (miRNAs) contribute significantly to autophagy in a variety of cancers. Previous studies have suggested that miR-129 functioned as an important inhibitor of the cell cycle and could promote the apoptosis of many cancer cell lines in vitro. Here, we reported that miR-129 acted as a potent inducer of autophagy. Forced expression of miR-129 could induce autophagic flux by targetedly suppressing Notch-1 in glioma cells. The autophagy induced by miR-129 could restrain the activity of mammalian target of rapamycin (mTOR) and upregulate Beclin-1. Moreover, we demonstrated that E2F transcription factor 7 (E2F7) could also trigger autophagic flux by upregulating Beclin-1 and mediating miR-129 induced autophagy. Additionally, knockdown of Notch-1 could upregulate the expression of E2F7, whereas downregulation of E2F7 alleviated shNotch-1-induced autophagic flux. In particular, knockdown of endogenous Beclin-1 could effectively reduce autophagic flux stimulated by miR-129 and E2F7. Interestingly, upon attenuation of miR-129- or E2F7-triggered autophagic flux rescued cell viability suppressed by them. More importantly, intratumoral injection of pHAGE miR-129 lentivirus in a nude mouse xenograft model significantly restrained tumor growth and triggered autophagy. In conclusion, these findings identify a new function for miR-129 as a potent inducer of autophagy through a novel Notch 1/E2F7/Beclin-1 axis in glioma. PMID- 26824183 TI - MicroRNA-497 impairs the growth of chemoresistant neuroblastoma cells by targeting cell cycle, survival and vascular permeability genes. AB - Despite multimodal therapies, a high percentage of high-risk neuroblastoma (NB) become refractory to current treatments, most of which interfere with cell cycle and DNA synthesis or function, activating the DNA damage response (DDR). In cancer, this process is frequently altered by deregulated expression or function of several genes which contribute to multidrug resistance (MDR). MicroRNAs are outstanding candidates for therapy since a single microRNA can modulate the expression of multiple genes of the same or different pathways, thus hindering the development of resistance mechanisms by the tumor. We found several genes implicated in the MDR to be overexpressed in high-risk NB which could be targeted by microRNAs simultaneously. Our functional screening identified several of those microRNAs that reduced proliferation of chemoresistant NB cell lines, the best of which was miR-497. Low expression of miR-497 correlated with poor patient outcome. The overexpression of miR-497 reduced the proliferation of multiple chemoresistant NB cell lines and induced apoptosis in MYCN-amplified cell lines. Moreover, the conditional expression of miR-497 in NB xenografts reduced tumor growth and inhibited vascular permeabilization. MiR-497 targets multiple genes related to the DDR, cell cycle, survival and angiogenesis, which renders this molecule a promising candidate for NB therapy. PMID- 26824184 TI - Does bevacizumab impact anti-EGFR therapy efficacy in metastatic colorectal cancer? AB - Anti-EGFR therapy and antiangiogenic therapies are used alone or in combination with chemotherapies to improve survival in metastatic colorectal cancer. However, it is unknown whether pretreatment with antiangiogenic therapy could impact on the efficacy of anti-EGFR therapy. We selected one hundred and twenty eight patients diagnosed with advanced colorectal cancer with a KRAS and NRAS unmutated tumor. These patients were treated with cetuximab or panitumumab alone or with chemotherapy as second or third-line. Univariate and multivariate Cox model analysis were performed to estimate the effect of a previous bevacizumab regimen on progression free survival and on overall survival during anti-EGFR therapy. In vitro studies using wild type KRAS and NRAS colon cancer cells were performed to evaluate the impact of VEGF-A on cetuximab-induced cell death. The median progression free survival (PFS) during anti-EGFR treatment was significantly different between the bevacizumab group and the non-bevacizumab group (2.8 and 4 months respectively; p = 0.003). The median overall survival from the beginning of the metastatic disease was similar in the two groups (41.3 and 42 months respectively; p = 0.7). In vitro, VEGF-A induced a resistance toward cetuximab cytotoxicity on three KRAS and NRAS wild type colon cancer cell lines in a VEGFR2 and Stat-3-dependent manner. All in all, our clinical data, supported by in vitro procedures, suggest that a previous anti-VEGF therapy decreases anti-EGFR efficacy. Although these results are observed in a limited cohort, they could be taken into consideration for a better strategy of care for patient suffering from metastatic colorectal cancer. PMID- 26824185 TI - Altered Hepa1-6 cells by dimethyl sulfoxide (DMSO)-treatment induce anti-tumor immunity in vivo. AB - Cancer immunotherapy is the use of the immune system to treat cancer. Our current research proposed an optional strategy of activating immune system involving in cancer immunotherapy. When being treated with 2% DMSO in culture medium, Hepa1-6 cells showed depressed proliferation with no significant apoptosis or decreased viability. D-hep cells, Hepa1-6 cells treated with DMSO for 7 days, could restore to the higher proliferation rate in DMSO-free medium, but alteration of gene expression profile was irreversible. Interestingly, tumors from D-hep cells, not Hepa1-6 cells, regressed in wild-type C57BL/6 mice whereas D-hep cells exhibited similar tumorigenesis as Hep1-6 cells in immunodeficient mice. As expected, additional Hepa1-6 cells failed to form tumors in the D-hep-C57 mice in which D hep cells were eliminated. Further research confirmed that D-hep-C57 mice established anti-tumor immunity against Hepa1-6 cells. Our research proposed viable tumor cells with altered biological features by DMSO-treatment could induce anti-tumor immunity in vivo. PMID- 26824186 TI - miR-143 or miR-145 overexpression increases cetuximab-mediated antibody-dependent cellular cytotoxicity in human colon cancer cells. AB - miR-143 and miR-145 are downregulated in colon cancer. Here, we tested the effect of restoring these miRNAs on sensitization to cetuximab in mutant KRAS (HCT116 and SW480) and wild-type KRAS (SW48) colon cancer cells. We evaluated cetuximab mediated antibody-dependent cellular cytotoxicity (ADCC) and the modulation of signaling pathways involved in immune effector cell-mediated elimination of cancer cells. Stable miR-143 or miR-145 overexpression increased cell sensitivity to cetuximab, resulting in a significant increase of cetuximab-mediated ADCC independently of KRAS status. Importantly, HCT116 cells overexpressing these miRNAs triggered apoptosis in result of cetuximab-mediated ADCC, effected by peripheral blood mononuclear cells (p < 0.01). This was associated with increased apoptosis and caspase-3/7 activity, and reduced Bcl-2 protein expression (p < 0.01). In addition, caspase inhibition abrogated cetuximab-mediated ADCC in HCT116 cells overexpressing either miR-143 or miR-145 (p < 0.01). Furthermore, Bcl-2 silencing led to high level of cetuximab-mediated ADCC, compared to control siRNA (p < 0.05). Importantly, granzyme B inhibition, abrogated cetuximab mediated ADCC, reducing caspase-3/7 activity (p < 0.01). Collectively, our data suggests that re-introduction of miR-143 or miR-145 may provide a new approach for development of therapeutic strategies to re-sensitize colon cancer cells to cetuximab by stimulating cetuximab-dependent ADCC to induce cell death. PMID- 26824187 TI - A 20(S)-protopanoxadiol derivative overcomes multi-drug resistance by antagonizing ATP-binding cassette subfamily B member 1 transporter function. AB - In cancer cells, failure of chemotherapy is often caused by the ATP-binding cassette subfamily B member 1 (ABCB1), and few drugs have been successfully developed to overcome ABCB1-mediated multi-drug resistance (MDR). To suppress ABCB1 activity, we previously designed and synthesized a new series of derivatives based on 20(S)-protopanoxadiol (PPD). In the present study, we investigated the role of PPD derivatives in the function of ABC transporters. Non toxic concentrations of the PPD derivative PPD12 sensitized ABCB1-overexpressing cells to their anti-cancer substrates better than either the parental PPD or inactive PPD11. PPD12 increased intracellular accumulation of adriamycin and rhodamine123 in resistant cancer cells. Although PPD12 did not suppress the expression of ABCB1 mRNA or protein, it stimulated the activity of ABCB1 ATPase. Because PPD12 is a competitive inhibitor, it was predicted to bind to the large hydrophobic cavity of homology-modeled human ABCB1. PPD12 also enhanced the efficacy of adriamycin against ABCB1-overexpressing KB/VCR xenografts in nude mice. In conclusion, PPD12 enhances the efficacy of substrate drugs in ABCB1 overexpressing cancer cells. These findings suggest that a combination therapy consisting of PPD12 with conventional chemotherapeutic agents may be an effective treatment for ABCB1-mediated MDR cancer patients. PMID- 26824188 TI - Identifying anti-cancer drug response related genes using an integrative analysis of transcriptomic and genomic variations with cell line-based drug perturbations. AB - BACKGROUND: Clinical responses to anti-cancer therapies often only benefit a defined subset of patients. Predicting the best treatment strategy hinges on our ability to effectively translate genomic data into actionable information on drug responses. RESULTS: To achieve this goal, we compiled a comprehensive collection of baseline cancer genome data and drug response information derived from a large panel of cancer cell lines. This data set was applied to identify the signature genes relevant to drug sensitivity and their resistance by integrating CNVs and the gene expression of cell lines with in vitro drug responses. We presented an efficient in-silico pipeline for integrating heterogeneous cell line data sources with the simultaneous modeling of drug response values across all the drugs and cell lines. Potential signature genes correlated with drug response (sensitive or resistant) in different cancer types were identified. Using signature genes, our collaborative filtering-based drug response prediction model outperformed the 44 algorithms submitted to the DREAM competition on breast cancer cells. The functions of the identified drug response related signature genes were carefully analyzed at the pathway level and the synthetic lethality level. Furthermore, we validated these signature genes by applying them to the classification of the different subtypes of the TCGA tumor samples, and further uncovered their in vivo implications using clinical patient data. CONCLUSIONS: Our work may have promise in translating genomic data into customized marker genes relevant to the response of specific drugs for a specific cancer type of individual patients. PMID- 26824189 TI - Detection of Rickettsia Species in Fleas Collected from Cats in Regions Endemic and Nonendemic for Flea-Borne Rickettsioses in California. AB - Rickettsia typhi, transmitted by rat fleas, causes most human flea-borne rickettsioses worldwide. Another rickettsia, Rickettsia felis, found in cat fleas, Ctenocephalides felis, has also been implicated as a potential human pathogen. In the continental United States, human cases of flea-borne rickettsioses are reported primarily from the southern regions of Texas and California where the cat flea is considered the principal vector. In California, more than 90% of locally acquired human cases are reported from suburban communities within Los Angeles and Orange counties despite the almost ubiquitous presence of cat fleas and their hosts throughout the state. The objective of this study is to assess the presence and infection rate of Rickettsia species in cat fleas from selected endemic and nonendemic regions of California. Cat fleas were collected from cats in Los Angeles County (endemic region) and Sacramento and Contra Costa counties (nonendemic region). Sequencing of 17 amplicons confirmed the presence of R. felis in both the endemic and non-endemic regions with a calculated maximum likelihood estimation of 131 and 234 per 1000 fleas, respectively. R. typhi was not detected in any flea pools. Two R. felis-like genotypes were also detected in fleas from Los Angeles County; Genotype 1 was detected in 1 flea pool and Genotype 2 was found in 10 flea pools. Genotype 1 was also detected in a single flea pool from Sacramento County. Results from this study show that R. felis is widespread in cat flea populations in both flea-borne rickettsioses endemic and nonendemic regions of California, suggesting that a high prevalence of this bacterium in cat fleas does not predispose to increased risk of human infection. Further studies are needed to elucidate the role of R. felis and the two R. felis-like organisms as etiologic agents of human flea-borne rickettsioses in California. PMID- 26824191 TI - Concerns about the safety of patients with diabetes insipidus admitted to hospital. PMID- 26824190 TI - Spider Silk Peptide Is a Compact, Linear Nanospring Ideal for Intracellular Tension Sensing. AB - Recent development and applications of calibrated, fluorescence resonance energy transfer (FRET)-based tension sensors have led to a new understanding of single molecule mechanotransduction in a number of biological systems. To expand the range of accessible forces, we systematically measured FRET versus force trajectories for 25, 40, and 50 amino acid peptide repeats derived from spider silk. Single molecule fluorescence-force spectroscopy showed that the peptides behaved as linear springs instead of the nonlinear behavior expected for a disordered polymer. Our data are consistent with a compact, rodlike structure that measures 0.26 nm per 5 amino acid repeat that can stretch by 500% while maintaining linearity, suggesting that the remarkable elasticity of spider silk proteins may in part derive from the properties of individual chains. We found the shortest peptide to have the widest range of force sensitivity: between 2 pN and 11 pN. Live cell imaging of the three tension sensor constructs inserted into vinculin showed similar force values around 2.4 pN. We also provide a lookup table for force versus intracellular FRET for all three constructs. PMID- 26824192 TI - The Importance of Clinical Phenotype in Understanding and Preventing Spontaneous Preterm Birth. AB - Spontaneous preterm birth (SPTB) is a well-known cause of maternal and neonatal morbidity. The search for the underlying pathways, documentation of the genetic causes, and identification of markers of spontaneous PTB have been marginally successful due to the fact that it is highly complex, with numerous processes that lead to a final common pathway. There is a great need for a comprehensive, consistent, and uniform classification system, which will be useful in identifying mechanisms, assigning prognosis, aiding in clinical management, and can identify areas of interest for intervention and future study. Effective classification systems must overcome obstacles including the lack of widely accepted definitions and uncertainty about inclusion of classifying features (e.g., presentation at delivery and multiple gestations) and levels of detail of these features. The optimal classification system should be based on the clinical phenotype, including characteristics of the mother, fetus, placenta, and the presentation for delivery. We present a proposed phenotyping system for spontaneous PTB. Future classification systems must establish a universally accepted set of definitions and a standardized clinical workup for all PTBs including the minimum clinical data to be collected and the laboratory and pathologic evaluation that should be completed. PMID- 26824193 TI - Breath gas concentrations mirror exposure to sevoflurane and isopropyl alcohol in hospital environments in non-occupational conditions. AB - Anaesthetic gases and disinfectants are a primary source of air contamination in hospitals. A highly sensitive sorbent-trap methodology has been used to analyse exhaled breath samples with detection limits in the pptv range, which allows volatile organic compounds (VOCs) to be detected at significantly lower levels (5 6 orders of magnitude below) than the recommended exposure limits by different organizations. Two common VOCs used in hospital environments, isopropyl alcohol (IPA) and sevoflurane, have been evaluated. Forced-expiratory breath samples were obtained from 100 volunteers (24 hospital staff, 45 hospital visitors and 31 external controls). Significant differences for IPA were found between samples from volunteers who had not been in contact with hospital environments (mean value of 8.032 ppbv) and people staying (20.981 ppbv, p = 0.0002) or working (19.457 ppbv, p = 0.000 09) in such an environment. Sevoflurane, an anaesthetic gas routinely used as an inhaled anaesthetic, was detected in all samples from volunteers in the hospital environment but not in volunteers who had not been in recent contact with a hospital environment. The levels of sevoflurane were significantly higher (p = 0.000 24) among staff members (0.522 ppbv) than among visitors to the hospital (0.196 ppbv). We conclude that highly sensitive methods are required to detect anaesthetic gas contamination in hospital environments. PMID- 26824194 TI - MRI-based determination of convex or concave surgical approach for lateral lumbar interbody fusion in lumbar degenerative scoliosis: a retrospective radiographic comparative analysis. AB - BACKGROUND: We determined the optimal approach to perform lateral lumbar interbody fusion (LLIF) to treat lumbar degenerative scoliosis (LDS) by comparing the safe zone and psoas muscle on the concave and convex sides. METHODS: Patients without scoliosis (N.=52) and those with levoscoliosis (N.=55) and dextroscoliosis (N.=53) were included. Vertebral anteroposterior diameter, overlap between the retroperitoneal vessels and the anterior edge of the vertebra, and overlap between the ventral nerve roots and the posterior edge of the vertebra were measured, and safe zones were calculated. The cross-sectional area (CSA) and fatty infiltration (FI) rate of the bilateral psoas muscle were measured, and the convex and concave sides were compared. RESULTS: The ventral overlap on the convex side decreased at the L3-4 and L4-5 levels in the levoscoliosis group (P=0.05 and P=0.01, respectively) and at the L2-3 and L3-4 levels in the dextroscoliosis group (P=0.01 and P=0.03, respectively). The convex side at the L3-4 and L4-5 levels presented a greater safe zone in the levoscoliosis group (76.11% vs. 74.00% at L3-4, P=0.02; 69.37% vs. 63.16% at L4 5, P=0.00). The convex side at the L2-3, L3-4, and L4-5 levels in the dextroscoliosis group showed greater safe zones compared to those in the group without scoliosis (77.78% vs. 74.40% at L2-3, P=0.02; 72.15% vs. 69.87% at L3-4, P=0.03; and 58.45% vs. 54.39% L4-5 level, P=0.01). CSA of the psoas muscle on the concave side was significantly higher at the L2-3 and L3-4 levels (P=0.02 and 0.01, respectively). The psoas muscle on the concave side was significantly thicker (P=0.00 at all levels) with a higher FI rate. CONCLUSIONS: The convex retroperitoneal vessels were positioned more anteriorly, whereas the ventral nerve roots lacked significant positional alterations, increasing the convex safe zone and providing optimal disc space access and less psoas muscle injury. PMID- 26824195 TI - Rationale for intraoperative radiotherapy in glioblastoma. AB - Glioblastoma is the most common and aggressive adult primary brain cancer. Despite multimodal therapy, it is associated with a survival of less than two years. Greater than 85% of recurrences occur within the original area of surgery and radiotherapy, suggesting a potential for improved local treatments. In addition to cancer cell invasion beyond surgical margins, a plethora of postinjury pro-proliferative stimuli are released from local healing brain, which both protect and nourish remaining cancer cells. This review compiles preclinical and clinical evidence for a dedicated treatment of both residual cancer cells and regional microenvironment using intraoperative radiotherapy (IORT). PMID- 26824196 TI - Prognostic implications of resection extent for patients with glioblastoma multiforme: a meta-analysis. AB - INTRODUCTION: Surgery is the primary treatment of glioblastoma multiforme (GBM), and a greater extent of resection (EOR) has been shown to be associated with improved survival. Our objective was to perform a meta-analysis comparing the 1 year overall survival (OS) and 1-year progression-free survival (PFS) of GBM patients who receive total resection, incomplete resection, or biopsy only. EVIDENCE ACQUISITION: PubMed and the Cochrane databases were searched until May 19th, 2015 using the terms "glioblastoma/glioblastoma multiforme," "extent of resection," "surgery prognosis/prognostic," "survival rate." Randomized controlled trials (RCTs), two-arm prospective studies, retrospective studies, and cohort studies reporting OS and/or PFS data were included. One-year OS and 1-year PFS were compared. EVIDENCE SYNTHESIS: Three prospective/RCTs, and 3 retrospective studies were included. The 6 studies included 1618 patients: 523 underwent total resections, 857 underwent incomplete resections, and 238 had biopsies. Total resection was associated with greater 1-year OS than incomplete resection (pooled odds ratio [OR] 1.89, 95% confidence interval [CI]: 1.35-2.64, P<0.001), and greater 1-year PFS than incomplete resection (pooled OR 2.11, 95% CI: 1.44-3.09, P<0.001). Analysis by study type (RCT or retrospective) produced similar results, although only one RCT provided 1-year PFS data and there was no significant difference between total resection and incomplete resection in that study. All analyses showed that total resection was associated with greater survival than biopsy only. CONCLUSIONS: Total resection of GBM is associated with improved OS and PFS as compared to incomplete resection or biopsy. PMID- 26824198 TI - Self-Care: Taking Care of Ourselves to Optimize the Care We Provide. PMID- 26824197 TI - Physical activity, psychiatric distress, and interest in exercise group participation among individuals seeking methadone maintenance treatment with and without chronic pain. AB - BACKGROUND AND OBJECTIVES: Physical activity may improve chronic pain, anxiety, and depression, which are prevalent among patients in methadone maintenance treatment (MMT), but relatively little is known about the physical activity levels or interest in exercise of patients in MMT. METHODS: We used a brief self report instrument to assess physical activity levels, chronic pain, psychiatric distress, and interest in exercise group participation among 303 adults seeking MMT. RESULTS: Most (73%) reported no moderate or vigorous intensity physical activity in the past week; 27% met recommended physical activity levels, and 24% reported interest in exercise group participation. Participants with (compared to those without) chronic pain had higher levels of psychiatric distress and were less likely to meet recommended levels of physical activity (p < .05), but did not differ significantly in their interest in participating in an exercise group. Participants who met recommended levels of physical activity in the past week were more likely to be men and had lower levels of depression than others (p < .05). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Low levels of physical activity and low interest in exercise group participation among patients entering MMT point to the need for and likely challenges of implementing exercise interventions in MMT. PMID- 26824199 TI - Utilizing Task Shifting to Increase Access to Maternal and Infant Health Interventions: A Case Study of Midwives for Haiti. AB - The shortage of health workers worldwide has been identified as a barrier to achieving targeted health goals. Task shifting has been recommended by the World Health Organization to increase access to trained and skilled birth attendants. One example of task shifting is the use of cadres of health care workers, such as nurses and auxiliary nurse-midwives, who can successfully deliver skilled care to women and infants in low-resource areas where women would otherwise lack access to critical health interventions during the childbearing years. Midwives for Haiti is an organization demonstrating the use of task shifting in its education program for auxiliary midwives. Graduates of the Midwives for Haiti education program are employed and working with women in hospitals, birth centers, and clinics across Haiti. This article reviews the Midwives for Haiti education program and presents successes and challenges in task shifting as a strategy to increase access to skilled maternal and newborn care and to meet international health goals to reduce maternal and infant mortality in a low-resource country. PMID- 26824200 TI - FETAL GROWTH PATTERNS VARY AMONG RACIAL/ETHNIC GROUPS. PMID- 26824201 TI - DROP IN RATES OF CHLAMYDIA TESTING ATTRIBUTED TO LESS FREQUENT CERVICAL CANCER SCREENING. PMID- 26824202 TI - USE OF COMPOUNDED HORMONE THERAPY IS WIDESPREAD IN THE UNITED STATES, AND FUTHER DATA ARE NEEDED TO IDENTIFY POTENTIAL RISKS. PMID- 26824203 TI - PUBLICATIONS ON YOGA AS COMPLEMENTARY THERAPY SURGE, BUT MORE HIGH-QUALITY STUDIES ARE NEEDED TO EFFECT HEALTH POLICY CHANGE. PMID- 26824204 TI - RISK-BASED SCREENING FOR CHLAMYDIA AND GONORRHEA PRIOR TO INTRAUTERINE DEVICE INSERTION MISSES FEW CASES. PMID- 26824205 TI - REFRESHING UPDATE ON IRON-DEFICIENCY ANEMIA. PMID- 26824208 TI - Sialoendoscopy: state of the art, challenges and further perspectives. Round Table, 101(st) SIO National Congress, Catania 2014. AB - This draft of the Official Round Table held during the 101(st) SIO National Congress is an updated review on sialoendoscopy, a technique used for diagnosis and treatment of obstructive pathologies of salivary glands in a minimally invasive fashion. This review treats many aspects of salivary gland endoscopy, starting from anatomy to deal with the more advanced surgical techniques and analyses the main decisional algorithms proposed in the literature. In addition, particular attention was directed to the current limitations of this technique and to the potential developments that sialoendoscopy could have in the near future. PMID- 26824209 TI - Clinicopathologic characteristics of familial versus sporadic papillary thyroid carcinoma. AB - It is unclear whether familial non-medullary thyroid carcinoma (FNMTC) is more aggressive than sporadic carcinoma, and its prevalence is still under debate. In this study, we investigated the clinicopathologic features of familial papillary thyroid carcinoma (PTC) compared with its sporadic counterpart. We used data from our hospital between 2008 and 2014 to compare the features of 24 familial PTC with 80 sporadic PTC. The prevalence of familial PTC was 1.5%; 25% of familial PTC exhibited a parent-offspring relationship, and 75% exhibited a sibling relationship. There were significant differences in terms of Hashimoto's thyroiditis, nodular goiter, multicentricity, bilaterality, histologic variant, T stage and N stage between the familial and sporadic PTC groups (all p < 0.05). When we compared sporadic PTC with parent-offspring or sibling familial PTC separately, parent-offspring familial PTC was more Hashimoto's thyroiditis and central LNM, while sibling familial PTC was more prevalent in multifocality and bilaterality than sporadic PTC. The recurrence rate was not significantly higher than that of sporadic PTC in familial PTC. The second generation in parent offspring familial PTC patients exhibited an earlier age at diagnosis, greater multifocality and a higher metastasis rate than the first generation. Based on our results, we conclude that familial PTC is a clinically distinct entity with an aggressive nature. Because of the frequent presence of benign nodules, multifocality, bilaterality and high rate of recurrence, total or near-total thyroidectomy with neck dissection in these patients might be recommended. To date, the optimal clinical treatment is yet to be established, but improved awareness and screening will permit earlier detection, more timely intervention and improved outcomes for patients and their families. PMID- 26824210 TI - Analysis of risk factors for pharyngocutaneous fistula after total laryngectomy with particular focus on nutritional status. AB - Pharyngocutaneous fistula (PCF) is the most common complication following total laryngectomy and the most difficult to manage. It often causes increased morbidity, delays starting adjuvant therapy, prolongs hospitalisation, increases treatment costs and reduces the quality of life (QoL). The objective of this study is to analyse the predisposing factors and the most important nutritional parameters related to the development of PCF in patients undergoing total laryngectomy and to suggest medical alternatives that might improve results. We performed a retrospective study of 69 patients who underwent either primary or salvage total laryngectomy in our department between January 2008 and January 2012. Risk factors for fistula formation were analysed including tumour characteristics (histology, grading, AJCC stage), treatment (primary or salvage surgery, extent of resection, flap reconstruction, preoperative radiotherapy), comorbidity and nutritional status (preoperative haemoglobin, albumin and prealbumin levels and their changes during hospitalisation). Twenty-four patients developed a PCF (overall incidence 34.8%). Fistula formation was significantly higher in patients with diabetes, preoperative malnutrition (identified from low preoperative albumin and prealbumin levels). After specific nutritional evaluation and support, no patient developed a PCF. Risk factors for PCF formation are extensively treated in the literature but identification of high risk patients is still controversial. Our study demonstrates that nutritional status of the patient, assessed by preoperative albumin, is also an important risk factor for PCF formation in addition to classical factors. Maintenance of a normal perioperative nutritional status can be helpful to avoid this complication. PMID- 26824211 TI - Musical training software for children with cochlear implants. AB - Although the voice in a free field has an excellent recruitment by a cochlear implant (CI), the situation is different for music because it is a much more complex process, where perceiving the pitch discrimination becomes important to appreciate it. The aim of this study is to determine the music perception abilities among children with Cis and to verify the benefit of a training period for specific musical frequency discrimination. Our main goals were to prepare a computer tool for pitch discrimination training and to assess musical improvements. Ten children, aged between 5 and 12 years, with optimal phoneme recognition in quiet and with no disabilities associated with deafness, were selected to join the training. Each patient received, before training period, two types of exams: a pitch discrimination test, consisting of discovering if two notes were different or not; and a music test consisting of two identification tasks (melodic and full version) of one music-item among 5 popular childhood songs. After assessment, a music training software was designed and utilised individually at home for a period of six months. The results following complete training showed significantly higher performance in the task of frequency discrimination. After a proper musical training identification, frequency discrimination performance was significantly higher (p < 0.001). The same considerations can be made in the identification of the songs presented in their melodic (p = 0.0151) and full songs version (p = 0.0071). Cases where children did not reach the most difficult level may be due to insufficient time devoted to training (ideal time estimated at 2-3 hours per week). In conclusion, this study shows that is possible to assess musical enhancement and to achieve improvements in frequency discrimination, following pitch discrimination training. PMID- 26824212 TI - Individualised headband simulation test for predicting outcome after percutaneous bone conductive implantation. AB - Trans-cutaneous bone conduction (BC) stimulators, when coupled to the HB (BC-HB), are generally used to predict the results that could be achieved after bone conductive implant (BCI) surgery, and their performance is generally considered inferior to that provided by the definitive percutaneous system. The aim of the present study was to compare the performances between BC-HB and BCI of the same typology, when the former's sound processor is fitted in accordance to the individual auditory situation. Twenty-two patients selected for surgical application of a BCI were evaluated and the same audiological protocol was used to select the candidate and assess the final outcome. The BC-HB was properly fitted based on individual hearing loss and personal auditory targets, and tested as primary step of the protocol to obtain the most reliable predictive value. The BAHA Divino and BP100 sound processors were applied in 12 patients with conductive/mixed hearing loss (CMHL) and in 10 subjects with single sided deafness (SSD). Audiometric evaluation included the pure tone average (PTA3) threshold between 250-1000 Hz; the PTA thresholds at 2000 and 4000 Hz; intelligibility scores as percentage of word recognition (WRS) in quiet and in noise; and subjective evaluation of perceived sound quality by a visual analogue scale (VAS). Statistical evaluation with a student's t test was used for assessment of efficacy of BC-HB and BCI compared with the unaided condition. Spearman's Rho coefficient was used to confirm the reliability of the BC-HB simulation test as a predictor of definitive outcome. The results showed that the mean PTA difference between BCI and BC-HB ranged from 2.54 to 8.27 decibels in the CMHL group and from 1.27 to 3.9 decibels in the SSD group. Compared with the BC-HB, BCI showed a better WRS both in CMHL (16% in quiet and 12% in noise) and in SSD (5% in quiet and a 1% in noise) groups. Spearman's Rho coefficient, calculated for PTA, WRS in quiet and in noise and VAS in the two aided conditions, showed a significant correlation between BC-HB and BCI, between PTA and VAS and between WRS in quiet and VAS. It is possible to conclude that the headband test, when the sound processor of the selected bone conductive implant is fitted and personalised for individual hearing loss and auditory targets of the candidate, may provide highly predictive data of the definitive outcome after BCI implant surgery. PMID- 26824213 TI - Foreign body injuries in children: a review. AB - The aim of this paper was to overview existing knowledge on foreign body (FB) injuries in children, with particular focus on FB types and anatomical locations, clinical presentation and complications. FB injuries represent a severe public health problem in childhood. The fact that the highest prevalence of FB injuries is reported for children between 0 and 3 years of age depends primarily on the fact that they explore objects using their mouth and are also not able to distinguish edible objects from non-edible ones. Types of FB causing injuries depend on the symptoms related to FB ingestion/inhalation/insertion (providing an early diagnosis of FB injuries) and complications related to the FB characteristics (type, shape, dimensions). The analysis of the Susy Safe database showed that in 10,564 cases, in which the object type was available, 74% of objects were inorganic and were mostly represented by pearls and balls, followed by coins. The main concerning about FB injuries is the fact that they may be asymptomatic or that symptoms may be non-specific. Consequently, the FB injury can be misinterpreted as a gastrointestinal or respiratory infection. The absence of specific symptoms indicating the occurrence of FB injury can lead to delays in diagnosis, thereby increasing the risk of complications. Symptoms seem to mostly depend on the anatomical location. Many ingested FBs pass naturally through the gastrointestinal tract without complications or damage. However, severe complications can occur depending on the characteristics of the FB, its anatomical location, the child's age and delays in diagnosis. PMID- 26824214 TI - Does the addition of a second daily session of hyperbaric oxygen therapy to intratympanic steroid influence the outcomes of sudden hearing loss? AB - The aim of this study is to investigate whether, in addition to intratympanic steroid therapy, additional hyperbaric oxygen therapy (HBOT) sessions per day (twice a day for 5 days) is more useful than one session per day for 10 days in patients affected by severe and profound idiopathic sudden sensorineural hearing loss (ISSNHL). A total of 55 patients affected by unilateral severe and profound ISSNHL were recruited. Two protocols were adopted. In the first, 27 patients (13 with profound and 14 with severe hearing loss) underwent one session of HBOT per day for 10 days, 6 days a week. An HBOT session comprised a period of 14 minutes air compression followed by 90 min at 2.4 atm absolute (ATA) followed by a decompression period of 15 min in oxygen. Patients breathed 100% oxygen through an appropriate mask checked for leaks. Patients were given 0.4 ml of 62.5 mg/ml of intratympanic prednisolone during the first three days of the protocol. In the second protocol, 28 patients (10 with profound and 18 with severe hearing loss) received 10 sessions of HBOT, twice a day for five days, 2.4 ATA 90 min 100% oxygen. The intratympanic injections of prednisolone were given between the two sessions of HBOT during the first three days of the protocol. Since there were no significant differences in hearing outcomes between the two protocols, the present study shows that the protocol of two sessions of HBOT per day is a valid treatment and equally effective as the one HBOT session per day, but with shorter treatment time. PMID- 26824215 TI - Quantification of cells expressing markers of proliferation and apoptosis in chronic tonsilitis. AB - During chronic tonsillitis, the relationship between proliferation and apoptosis of lymphocytes in tonsillar follicles can be disturbed, which gives rise to attenuation of tonsil immunocompetence and diminishing its contribution in systemic immunity. In this study, we have quantified the cells expressing the markers of proliferation and apoptosis in the follicles of the palatine tonsil. Six tonsils from patients aged 10-29 years with hypertrophic tonsillitis and five tonsils from patients aged 18-22 years with recurrent tonsillitis were studied. The sections of paraffin blocks of tonsillar tissue were stained by the immunohistochemical LSAB/HRP method with the utilisation of antibodies for: Ki-67 antigen-cell marker of proliferation; Bcl-2 and survivin anti-apoptotic factors and Fas/CD95, caspase-3 and Bax pro-apoptotic factors. The size of lymphoid follicles, i.e. mean follicle area and number of lymphoid follicle immunopositive cells per mm2 of a slice area, i.e. numerical areal density were determined by the quantitative image analysis. The localisation of Ki-67, Bcl-2, survivin, Fas/CD95, caspase-3 and Bax- immunopositive cells inside the palatine tonsil was similar in both types of tonsillitis. The number of Ki-67 immunopositive cells was significantly (p < 0.01) larger in the tonsils with hypertrophic tonsillitis (14681.4 +/- 1460.5) in comparison to those with recurrent tonsillitis (12491.4 +/- 2321.6), although the number of survivin and caspase-3 immunopositive cells was significantly (p < 0.05) larger in recurrent tonsillitis (survivin, 406.9 +/- 98.4; caspase-3, 350.4 +/- 119.4) when compared to those with hypertrophic tonsillitis (survivin, 117.4 +/- 14.5; caspase-3, 210 +/- 24). Our results show that the rate of the proliferation and apoptosis of follicular lymphocytes is different in various types of tonsillitis. This suggests that the immunological potential of the palatine tonsil varies in patients with hypertrophic and recurrent tonsillitis, which in practice poses a dilemma over the choice of conservative or surgical treatment. PMID- 26824216 TI - Correction of a mandibular asymmetry after fibula reconstruction using a custom made polyetheretherketone (PEEK) onlay after implant supported occlusal rehabilitation. AB - This study describes an unusual case of mandibular asymmetry after fibula free flap reconstruction in a young man following major facial trauma that was corrected using a custom-made polyetheretherketone prosthesis. There is little information in the literature on the use of alloplasts to correct mandibular asymmetry as interest in 'aesthetic re-modelling' has traditionally focused on nasal, zygomatic and chin regions. This report demonstrates that this technique can be used successfully to address selected cases of mandibular asymmetry. PMID- 26824217 TI - Parapharyngeal metastases from thyroid cancer: surgical management of two cases with minimally-invasive video-assisted technique. AB - Metastases to parapharyngeal or retropharyngeal lymph nodes are rare in well differentiated thyroid cancers. A review of English literature found only 112 cases reported in the last two decades, with an incidence of parapharyngeal lymph nodes metastases ranging from 0.43 to 2.5%. Surgical resection is the most effective treatment for patients with parapharyngeal lymph node metastasis from thyroid carcinoma. We describe two cases of thyroid cancer parapharyngeal lymph node metastases that were surgically removed using a traditional transcervical approach, with the help of a minimally-invasive video-assisted technique. A video assisted minimally-invasive transcervical approach is a new technique for excision of sizable benign tumours and selected malignant tumours. The endoscopic technique allows clear identification of critical surgical landmarks that guide the dissection through the correct cleavage plane in a nearly bloodless surgical field, thus decreasing the rate of complications. In both patients postoperative follow-up showed no sequelae and recurrence after 20 and 15 months from surgery. PMID- 26824218 TI - Giant pleomorphic adenoma of the parotid gland: an unusual case presentation and literature review. AB - Pleomorphic adenoma is the most common type of all salivary gland tumours. Although uncommon, cases of giant pleomorphic adenomas have been described in the medical literature, the majority involving the parotid gland. This paper describes an unusual case of a giant adenoma arising in the parotid gland. The patient underwent surgical resection of the giant tumour, which was one of the largest pleomorphic adenoma reported in recent literature. This case has prompted us to evaluate the behaviour of those benign tumours, which suggested that aesthetic and social morbidity is sufficient to justify, when possible, early tumour excision, despite the relatively low risk of malignant transformation. Management of this unusual tumour is discussed, and the literature on giant parotid tumours is reviewed. PMID- 26824219 TI - Minimally invasive surgical removal of an intracochlear schwannoma causing an intractable paroxysmal positional vertigo. AB - Intracochlear schwannomas are rare tumours. Diagnosis is based on high-resolution MRI, which should be used for accurate determination of the location of tumours. We report a case of a cochlear schwannoma that presented with profound hearing loss and intractable paroxysmal positional vertigo, which was diagnosed with gadolinium-enhanced MRI and removed using a transcanal minimally-invasive transotic approach. PMID- 26824220 TI - Depressive symptoms are associated with higher rates of readmission or mortality after medical hospitalization: A systematic review and meta-analysis. AB - Depressive symptoms during a medical hospitalization may be an overlooked prognostic factor for adverse events postdischarge. Our aim was to evaluate whether depressive symptoms predict 30-day readmission or death after medical hospitalization. We conducted a systematic review of studies that compared postdischarge outcomes by in-hospital depressive status. We assessed study quality and pooled published and unpublished data using random effects models. Overall, one-third of 6104 patients discharged from medical wards were depressed (interquartile range, 27%-40%). Compared to inpatients without depression, those discharged with depressive symptoms were more likely to be readmitted (20.4% vs 13.7%, risk ratio [RR]: 1.73, 95% confidence interval [CI]: 1.16-2.58) or die (2.8% vs 1.5%, RR: 2.13, 95% CI: 1.31-3.44) within 30 days. Depressive symptoms were common in medical inpatients and are associated with an increased risk of adverse events postdischarge. Journal of Hospital Medicine 2016;11:373-380. (c) 2016 The Authors Journal of Hospital Medicine published by Wiley Periodicals, Inc. on behalf of Society of Hospital Medicine. PMID- 26824221 TI - Functional cloning of a gp100-reactive T-cell receptor from vitiligo patient skin. AB - We isolated gp100-reactive T cells from perilesional skin of a patient with progressive vitiligo with superior reactivity toward melanoma cells compared with tumor-infiltrating lymphocytes 1520, a melanoma-derived T-cell line reactive with the same cognate peptide. After dimer enrichment and limited dilution cloning, amplified cells were subjected to reverse transcription and 5' RACE to identify the variable TCRalpha and TCRbeta subunit sequences. The full-length sequence was cloned into a retroviral vector separating both subunits by a P2A slippage sequence and introduced into Jurkat cells and primary T cells. Cytokine secreted by transduced cells in response to cognate peptide and gp100-expressing targets signifies that we have successfully cloned a gp100-reactive T-cell receptor from actively depigmenting skin. PMID- 26824222 TI - Zinc sensing by metal-responsive transcription factor 1 (MTF1) controls metallothionein and ZnT1 expression to buffer the sensitivity of the transcriptome response to zinc. AB - Only a small number of genes are known direct targets of the zinc-responsive transcription factor MTF1; therefore, the aim of this study was to gain a more complete understanding of the MTF-1 regulated zinc-responsive component of the transcriptome. A targeted siRNA was used to deplete MTF1 expression in the human intestinal cell line Caco-2. We predicted that the response to zinc of direct MTF1 target genes would be abrogated by MTF1 knockdown. Surprisingly, a greater number of genes were regulated by zinc following MFT1 knockdown, and most genes that responded to zinc under both control and MTF1-depleted conditions had an augmented response in the latter condition. Exceptions were the zinc effluxer ZnT1 and a suite of metallothionein genes, suggesting that responses of other genes to zinc are usually buffered by increases in these proteins. We propose that MTF1 heads a hierarchy of zinc sensors, and through controlling the expression of a raft of metallothioneins and other key proteins involved in controlling intracellular zinc levels (e.g. ZnT1) alters zinc buffering capacity and total cellular zinc content. We tested and validated this model by overexpressing metallothionein and observing the predicted curtailment in response of the zinc-repressed SLC30A5 (ZnT5) promoter. The model provides the framework for an integrated understanding of cellular zinc homeostasis. Because MTs can bind metals other than zinc, this framework links with overall cellular metal homeostasis. PMID- 26824223 TI - Systematic versus opportunistic risk assessment for the primary prevention of cardiovascular disease. AB - BACKGROUND: Screening programmes can potentially identify people at high cardiovascular risk and reduce cardiovascular disease (CVD) morbidity and mortality. However, there is currently not enough evidence showing clear clinical or economic benefits of systematic screening-like programmes over the widely practised opportunistic risk assessment of CVD in primary care settings. OBJECTIVES: The primary objective of this review was to assess the effectiveness, costs and adverse effects of systematic risk assessment compared to opportunistic risk assessment for the primary prevention of CVD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on the Cochrane Library, MEDLINE, EMBASE on 30 January 2015, and Web of Science Core Collection and additional databases on the Cochrane Library on 4 December 2014. We also searched two clinical trial registers and checked reference lists of relevant articles. We applied no language restrictions. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) that assessed the effects of systematic risk assessment, defined as a screening-like programme involving a predetermined selection process of people, compared with opportunistic risk assessment which ranged from no risk assessment at all to incentivised case finding of CVD and related risk factors. Participants included healthy adults from the general population, including those who are at risk of CVD. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies. One review author extracted data and assessed them for risk of bias and a second checked them. We assessed evidence quality using the GRADE approach and present this in a 'Summary of findings' table. MAIN RESULTS: Nine completed RCTs met the inclusion criteria, of which four were cluster-randomised. We also identified five ongoing trials. The included studies had a high or unclear risk of bias, and the GRADE ratings of overall quality were low or very low. The length of follow-up varied from one year in four studies, three years in one study, five or six years in two studies, and ten years in two studies. Eight studies recruited participants from the general population, although there were differences in the age ranges targeted. One study recruited family members of cardiac patients (high risk assessment). There were considerable differences between the studies in the interventions received by the intervention and control groups. There was insufficient evidence to stratify by the types of risk assessment approaches.Limited data were available on all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.92 to 1.02; 3 studies,103,571 participants, I2 = 0%; low-quality evidence) and cardiovascular mortality (RR 1.00, 95% CI 0.90 to 1.11; 2 studies, 43,955 participants, I2 = 0%), and suggest that screening has no effect on these outcomes. Data were also limited for combined non-fatal endpoints; overall, evidence indicates no difference in total coronary heart disease (RR 1.01, 95% CI 0.95 to 1.07; 4 studies, 5 comparisons, 110,168 participants, I2 = 0%; low quality evidence), non-fatal coronary heart disease (RR 0.98, 95% CI 0.89 to 1.09; 2 studies, 43,955 participants, I2 = 39%), total stroke (RR 0.99, 95% CI 0.90 to 1.10; 2 studies, 79,631 participants, I2 = 0%, low-quality evidence), and non-fatal stroke (RR 1.17, 95% CI 0.94 to 1.47; 1 study, 20,015 participants).Overall, systematic risk assessment appears to result in lower total cholesterol levels (mean difference (MD) -0.11 mmol/l, 95% CI -0.17 to 0.04, 6 studies, 7 comparisons, 12,591 participants, I2 = 57%; very low-quality evidence), lower systolic blood pressure (MD -3.05 mmHg, 95% CI -4.84 to -1.25, 6 studies, 7 comparisons, 12,591 participants, I2 = 82%; very low-quality evidence) and lower diastolic blood pressure (MD -1.34 mmHg, 95% CI -1.76 to -0.93, 6 studies, 7 comparisons, 12,591 participants, I2 = 0%; low-quality evidence). One study assessed adverse effects and found no difference in psychological distress at five years (1126 participants). AUTHORS' CONCLUSIONS: The results are limited by the heterogeneity between trials in terms of participants recruited, interventions and duration of follow-up. Limited data suggest that systematic risk assessment for CVD has no statistically significant effects on clinical endpoints. There is limited evidence to suggest that CVD systematic risk assessment may have some favourable effects on cardiovascular risk factors. The completion of the five ongoing trials will add to the evidence base. PMID- 26824224 TI - Determining carotid plaque vulnerability using ultrasound center frequency shifts. AB - BACKGROUND: The leading cause of morbidity and mortality worldwide is atherosclerotic cardiovascular disease, most commonly caused by rupture of a high risk plaque and subsequent thrombosis resulting in stroke, myocardial infarction or sudden death depending on the affected arterial territory. Accurate, non invasive methods to identify such lesions known as vulnerable or high-risk plaques are currently sub-optimal. Our aim was to validate a new non-invasive ultrasound method to identify high-risk carotid plaques. METHODS: We evaluated a new method based on the center frequency shift (CFS) of the ultrasound radio frequency data obtained from carotid plaques compared to a reference phantom. We evaluated the method both ex vivo, on 157 sections from 18 plaques, and in vivo, in 39 patients 1-day prior to carotid plaque removal, and correlated the data with histology. RESULTS: The CFS correlated with a plaque vulnerability index based on histological areas stained for lipids, macrophages, hemorrhage, smooth muscle cells and collagen (r = -0.726, P = 1.7 * 10(-8)). Plaques with CFS below median had larger cores, more macrophages and were less rich in collagen in agreement with the definition of rupture-prone plaques. The accuracy to detect plaques with high vulnerability index was 78% (confidence interval (CI) 61-89%), with sensitivity 77% (CI 61-89%) and specificity 78% (CI 62-89%). CONCLUSIONS: Our method is the first to characterize atherosclerotic plaque components that affect plaque vulnerability using CFS. PMID- 26824225 TI - Paradoxical Ventriculophasic Arrhythmia in a Patient with 2:1 Atrioventricular Block: A Rare Phenomenon. PMID- 26824226 TI - PRRX2 as a novel TGF-beta-induced factor enhances invasion and migration in mammary epithelial cell and correlates with poor prognosis in breast cancer. AB - TGF-beta and cancer progression share a multifaceted relationship. Despite the knowledge of TGF-beta biology in the development of cancer, several factors that mediate the cancer-promoting role of TGF-beta continue to be identified. This study aimed to identify and characterise novel factors potentially related to TGF beta-mediated tumour aggression in breast cells. We treated the human mammary epithelial cell line MCF10A with TGF-beta and identified TGF-beta-dependent upregulation of PRRX2, the gene encoding paired-related homeobox 2 transcription factor. Overexpression of PRRX2 enhanced migration, invasion and anchorage independent growth of MCF10A cells and induced partial epithelial mesenchymal transition (EMT), as determined by partial fibroblastoid morphology of cells, upregulation of EMT markers and partially disrupted acinar structure in a three dimensional culture. We further identified PLAT, the gene encoding tissue-type plasminogen activator (tPA), as the highest differentially expressed gene in PRRX2-overexpressing MCF10A cells, and demonstrated direct binding and transactivation of the PLAT promoter by PRRX2. Furthermore, PLAT knockdown inhibited PRRX2-mediated enhanced migration and invasion, suggesting that tPA may mediate PRRX2-induced migration and invasion. Finally, the significant correlation of PRRX2 expression with poor survival in 118 primary breast tumour samples (P = 0.027) and the increased PRRX2 expression in metaplastic breast carcinoma samples, which is pathogenetically related to EMT, validated the biological importance of PRRX2-enhanced migration and invasion and PRRX2-induced EMT. Thus, our data suggest that upregulation of PRRX2 may be a mechanism contributing to TGF-beta-induced invasion and EMT in breast cancer. (c) 2016 Wiley Periodicals, Inc. PMID- 26824227 TI - Risk for Opioid Misuse Among Emergency Department Cancer Patients. AB - OBJECTIVES: One of the most challenging areas of emergency medicine practice is the management and treatment of severe and persistent pain, including cancer related pain. Emergency departments (EDs) in the United States frequently provide care for patients with cancer and an increasing concern is the potential for opioid misuse in this patient group. The authors determined the risk for opioid misuse among ED cancer patients with pain and assessed demographic and clinical factors associated with increased misuse risk. The Texas state prescription monitoring program was also queried for evidence of multiple opioid prescriptions for comparing low- and high-risk groups. METHODS: The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) was administered to assess risk for opioid misuse among cancer patients presenting to the ED of a comprehensive cancer center in the United States. Eligibility criteria included: 1) presentation for treatment of chronic cancer-related pain while taking a prescribed schedule II opioid for analgesia, 2) age of 18 years or older, 3) ability to speak English, and 4) ability to understand the study and give written informed consent. RESULTS: Of 934 ED patients screened for the study, 290 were eligible and 209 participated (72% response rate). On the basis of the recommended SOAPP-R cutoff score of 18, a total of 71 of the 209 patients (34%) were categorized as having a high risk of misuse. Of note, 15% and 4% of all patients reported past or current use of illicit substances, respectively. The total number of annual opioid prescriptions (17.8 vs. 12.6; p = 0.023) differed between the high- versus low-risk groups. Multivariable analyses showed that depression (odds ratio [OR] = 3.06, 95% confidence interval [CI] = 1.45 to 6.48; p = 0.003), poor coping (OR = 1.08, 95% CI = 1.03 to 1.13; p = 0.001), and illicit substance use (OR = 28.30, 95% CI = 2.97 to 269.24; p = 0.029) were significantly associated with high risk of opioid misuse. CONCLUSIONS: The risk of opioid misuse among cancer patients is substantial. Screening for opioid misuse in the ED is feasible. PMID- 26824229 TI - Correction: MicroRNA-486 as a Biomarker for Early Diagnosis and Recurrence of Non Small Cell Lung Cancer. PMID- 26824228 TI - Burden of Hospital Acquired Infections and Antimicrobial Use in Vietnamese Adult Intensive Care Units. AB - BACKGROUND: Vietnam is a lower middle-income country with no national surveillance system for hospital-acquired infections (HAIs). We assessed the prevalence of hospital-acquired infections and antimicrobial use in adult intensive care units (ICUs) across Vietnam. METHODS: Monthly repeated point prevalence surveys were systematically conducted to assess HAI prevalence and antimicrobial use in 15 adult ICUs across Vietnam. Adults admitted to participating ICUs before 08:00 a.m. on the survey day were included. RESULTS: Among 3287 patients enrolled, the HAI prevalence was 29.5% (965/3266 patients, 21 missing). Pneumonia accounted for 79.4% (804/1012) of HAIs Most HAIs (84.5% [855/1012]) were acquired in the survey hospital with 42.5% (363/855) acquired prior to ICU admission and 57.5% (492/855) developed during ICU admission. In multivariate analysis, the strongest risk factors for HAI acquired in ICU were: intubation (OR 2.76), urinary catheter (OR 2.12), no involvement of a family member in patient care (OR 1.94), and surgery after admission (OR 1.66). 726 bacterial isolates were cultured from 622/1012 HAIs, most frequently Acinetobacter baumannii (177/726 [24.4%]), Pseudomonas aeruginosa (100/726 [13.8%]), and Klebsiella pneumoniae (84/726 [11.6%]), with carbapenem resistance rates of 89.2%, 55.7%, and 14.9% respectively. Antimicrobials were prescribed for 84.8% (2787/3287) patients, with 73.7% of patients receiving two or more. The most common antimicrobial groups were third generation cephalosporins, fluoroquinolones, and carbapenems (20.1%, 19.4%, and 14.1% of total antimicrobials, respectively). CONCLUSION: A high prevalence of HAIs was observed, mainly caused by Gram-negative bacteria with high carbapenem resistance rates. This in combination with a high rate of antimicrobial use illustrates the urgent need to improve rational antimicrobial use and infection control efforts. PMID- 26824230 TI - Prognostic Value of Cavernous Sinus Invasion in Patients with Nasopharyngeal Carcinoma Treated with Intensity-Modulated Radiotherapy. AB - PURPOSE: To investigate the prognostic value of cavernoussinus invasion (CSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). PATIENTS AND METHODS: Retrospective review of data from 1,087 patients with biopsy-proven, non-metastatic NPC. All patients were diagnosed using magnetic resonance imaging (MRI) scans and received IMRT as the primary treatment. RESULTS: The incidence of cavernoussinus invasion in this cohort was 12.1%. In univariate analysis, 5-year overall survival (OS) (70.6% vs. 88.5%, P < 0.001) and distant metastasis-free survival (DMFS) (71.4% vs. 87.7%, P < 0.001), but not locoregional relapse-free survival (LRFS) (93.9% vs. 93.7%, P = 0.341), were significantly different between patients with and without cavernoussinus invasion. In the T4 subgroup, the 5-year OS, DMFS, and LRFS of patients with and without cavernoussinus extension were 70.6% vs. 81.9% (P = 0.011), 71.4% vs. 84.1% (P = 0.011), and 91.2% vs. 89.7% (P = 0.501), respectively. In multivariate analysis, cavernoussinus invasion was an independent prognostic factor for poorer OS (HR = 1.782; P = 0.013) and DMFS (HR = 1.771; P = 0.016), but not LRFS (HR = 0.632; P = 0.294). In patients with lymph node metastasis, the DMFS rates of patients with and without cavernoussinus invasion were significantly different (P < 0.001). Preliminaryanalysis indicated that neoadjuvant chemotherapy led to better DMFS and OS in patients with cavernoussinus invasion than concurrent chemotherapy or radiotherapy alone; however, the differences were not significant. CONCLUSIONS: In the IMRT era, cavernoussinus invasion remains a prognostic factor for poor DMFS and OS in NPC, even in patients with T4 disease. PMID- 26824231 TI - Dietary Supplementation with Organoselenium Accelerates Recovery of Bladder Expression, but Does Not Improve Locomotor Function, following Spinal Cord Injury. AB - Selenium is an essential element required for activity of several antioxidant enzymes, including glutathione peroxidase. Because of the critical role of the antioxidant system in responding to traumatic events, we hypothesized that dietary selenium supplementation would enhance neuroprotection in a rodent model of spinal cord injury. Rats were maintained on either a control or selenium enriched diet prior to, and following, injury. Dietary selenium supplementation, provided as selenized yeast added to normal rat chow, resulted in a doubling of selenium levels in the spinal cord. Dietary selenium reduced the time required for recovery of bladder function following thoracic spinal cord injury. However, this was not accompanied by improvement in locomotor function or tissue sparing. PMID- 26824232 TI - Prader-Willi Critical Region, a Non-Translated, Imprinted Central Regulator of Bone Mass: Possible Role in Skeletal Abnormalities in Prader-Willi Syndrome. AB - Prader-Willi Syndrome (PWS), a maternally imprinted disorder and leading cause of obesity, is characterised by insatiable appetite, poor muscle development, cognitive impairment, endocrine disturbance, short stature and osteoporosis. A number of causative loci have been located within the imprinted Prader-Willi Critical Region (PWCR), including a set of small non-translated nucleolar RNA's (snoRNA). Recently, micro-deletions in humans identified the snoRNA Snord116 as a critical contributor to the development of PWS exhibiting many of the classical symptoms of PWS. Here we show that loss of the PWCR which includes Snord116 in mice leads to a reduced bone mass phenotype, similar to that observed in humans. Consistent with reduced stature in PWS, PWCR KO mice showed delayed skeletal development, with shorter femurs and vertebrae, reduced bone size and mass in both sexes. The reduction in bone mass in PWCR KO mice was associated with deficiencies in cortical bone volume and cortical mineral apposition rate, with no change in cancellous bone. Importantly, while the length difference was corrected in aged mice, consistent with continued growth in rodents, reduced cortical bone formation was still evident, indicating continued osteoblastic suppression by loss of PWCR expression in skeletally mature mice. Interestingly, deletion of this region included deletion of the exclusively brain expressed Snord116 cluster and resulted in an upregulation in expression of both NPY and POMC mRNA in the arcuate nucleus. Importantly, the selective deletion of the PWCR only in NPY expressing neurons replicated the bone phenotype of PWCR KO mice. Taken together, PWCR deletion in mice, and specifically in NPY neurons, recapitulates the short stature and low BMD and aspects of the hormonal imbalance of PWS individuals. Moreover, it demonstrates for the first time, that a region encoding non-translated RNAs, expressed solely within the brain, can regulate bone mass in health and disease. PMID- 26824234 TI - New Sections for the New Year. PMID- 26824233 TI - Characterization and Expression of the Lucina pectinata Oxygen and Sulfide Binding Hemoglobin Genes. AB - The clam Lucina pectinata lives in sulfide-rich muds and houses intracellular symbiotic bacteria that need to be supplied with hydrogen sulfide and oxygen. This clam possesses three hemoglobins: hemoglobin I (HbI), a sulfide-reactive protein, and hemoglobin II (HbII) and III (HbIII), which are oxygen-reactive. We characterized the complete gene sequence and promoter regions for the oxygen reactive hemoglobins and the partial structure and promoters of the HbI gene from Lucina pectinata. We show that HbI has two mRNA variants, where the 5'end had either a sequence of 96 bp (long variant) or 37 bp (short variant). The gene structure of the oxygen reactive Hbs is defined by having 4-exons/3-introns with conservation of intron location at B12.2 and G7.0 and the presence of pre-coding introns, while the partial gene structure of HbI has the same intron conservation but appears to have a 5-exon/ 4-intron structure. A search for putative transcription factor binding sites (TFBSs) was done with the promoters for HbII, HbIII, HbI short and HbI long. The HbII, HbIII and HbI long promoters showed similar predicted TFBSs. We also characterized MITE-like elements in the HbI and HbII gene promoters and intronic regions that are similar to sequences found in other mollusk genomes. The gene expression levels of the clam Hbs, from sulfide rich and sulfide-poor environments showed a significant decrease of expression in the symbiont-containing tissue for those clams in a sulfide-poor environment, suggesting that the sulfide concentration may be involved in the regulation of these proteins. Gene expression evaluation of the two HbI mRNA variants indicated that the longer variant is expressed at higher levels than the shorter variant in both environments. PMID- 26824236 TI - Evolutionary Divergences in Root Exudate Composition among Ecologically Contrasting Helianthus Species. AB - Plant roots exude numerous metabolites into the soil that influence nutrient availability. Although root exudate composition is hypothesized to be under selection in low fertility soils, few studies have tested this hypothesis in a phylogenetic framework. In this study, we examined root exudates of three pairs of Helianthus species chosen as phylogenetically-independent contrasts with respect to native soil nutrient availability. Under controlled environmental conditions, seedlings were grown to the three-leaf-pair stage, then transferred to either high or low nutrient treatments. After five days of nutrient treatments, we used gas chromatography-mass spectrometry for analysis of root exudates, and detected 37 metabolites across species. When compared in the high nutrient treatment, species native to low nutrient soils exhibited overall higher exudation than their sister species native to high nutrient soils in all three species pairs, providing support for repeated evolutionary shifts in response to native soil fertility. Species native to low nutrient soils and those native to high nutrient soils responded similarly to low nutrient treatments with increased exudation of organic acids (fumaric, citric, malic acids) and glucose, potentially as a mechanism to enhance nutrition acquisition. However, species native to low nutrient soils also responded to low nutrient treatments with a larger decrease in exudation of amino acids than species native to high nutrient soils in all three species pairs. This indicates that species native to low nutrient soils have evolved a unique sensitivity to changes in nutrient availability for some, but not all, root exudates. Overall, these repeated evolutionary divergences between species native to low nutrient soils and those native to high nutrient soils provide evidence for the adaptive value of root exudation, and its plasticity, in contrasting soil environments. PMID- 26824237 TI - Gestational Diabetes Mellitus. AB - Based on the Hyperglycemia and Adverse Pregnancy Outcome study, new universal screening recommendations and cut-offs for gestational diabetes mellitus (GDM) have been proposed. In addition to the immediate perinatal risk, GDM carries an increased risk of metabolic disease in the mother and child. Maternal obesity has even been shown to be associated with increased all-cause mortality in offspring. In addition to known risk factors, excessive gestational weight gain, increased fat consumption, a low vitamin D level, psychological stress and negative mood are risk factors for GDM. Regarding therapy, the US Preventive Task Force concluded in 2013 that GDM treatment significantly reduces the risks of pre eclampsia, macrosomia and shoulder dystocia (relative risks of 0.62, 0.5 and 0.42, respectively). Although nutrition therapy represents a cornerstone in GDM management, the results of studies are not clear regarding which types of dietary advice are the most suitable. Most physical activity interventions improve glucose control and/or reduce insulin use. Recent studies have evaluated and provided more information about treatment with metformin or glyburide. Postpartum management is essential and should focus on long-term screening and diabetes prevention strategies. PMID- 26824239 TI - The 'Old' Anti-Diabetic Agents: A Systematic Inventory. AB - An array of oral agents is available for the treatment of hyperglycaemia in type 2 diabetes. This systematic inventory focuses on 'old' oral agents, including metformin, sulfonylureas (SUs), thiazolidinediones, alpha glucosidase inhibitors, and meglitinides. Twelve meta-analyses and six randomized controlled trials that used patient-relevant outcomes as primary endpoints were critically reviewed. Guidelines recommend the use of metformin or an SU as the first-line pharmacotherapeutic options. Beneficial effects of metformin have been demonstrated for 'any diabetes-related endpoint' and 'all-cause mortality' in small study groups of overweight and obese patients with newly manifested type 2 diabetes. Various SU agents are available, for which a class effect has clearly been disproven. Beneficial effects have only been demonstrated for glyburide in preventing microvascular complications. Thiazolidinediones have been withdrawn from the markets in some countries. Meta-analyses found an increased coronary risk for rosiglitazone. The benefit-to-risk ratios of alpha glucosidase inhibitors and meglitinides regarding hard endpoints remain uncertain. Diabetes treatment is complex and individualised. We identified several studies focusing on the efficacy of treatment policies rather than on single drug effects. However, as long as the efficacy of single agents regarding hard clinical endpoints is unclear, interpretation of study results on treatment policies remains speculative. PMID- 26824238 TI - Mice Abundant in Muricholic Bile Acids Show Resistance to Dietary Induced Steatosis, Weight Gain, and to Impaired Glucose Metabolism. AB - High endogenous production of, or treatment with muricholic bile acids, strongly reduces the absorption of cholesterol. Mice abundant in muricholic bile acids may therefore display an increased resistance against dietary induced weight gain, steatosis, and glucose intolerance due to an anticipated general reduction in lipid absorption. To test this hypothesis, mice deficient in steroid 12-alpha hydroxylase (Cyp8b1-/-) and therefore abundant in muricholic acids were monitored for 11 weeks while fed a high fat diet. Food intake and body and liver weights were determined, and lipids in liver, serum and feces were measured. Further, responses during oral glucose and intraperitoneal insulin tolerance tests were evaluated. On the high fat diet, Cyp8b1-/- mice displayed less weight gain compared to wildtype littermates (Cyp8b1+/+). In addition, liver enlargement with steatosis and increases in serum LDL-cholesterol were strongly attenuated in Cyp8b1-/- mice on high fat diet. Fecal excretion of cholesterol was increased and there was a strong trend for doubled fecal excretion of free fatty acids, while excretion of triglycerides was unaltered, indicating dampened lipid absorption. On high fat diet, Cyp8b1-/- mice also presented lower serum glucose levels in response to oral glucose gavage or to intraperitoneal insulin injection compared to Cyp8b1+/+. In conclusion, following exposure to a high fat diet, Cyp8b1-/- mice are more resistant against weight gain, steatosis, and to glucose intolerance than Cyp8b1+/+ mice. Reduced lipid absorption may in part explain these findings. Overall, the results suggest that muricholic bile acids may be beneficial against the metabolic syndrome. PMID- 26824240 TI - Targeted Cooperative Actions Shape Social Networks. AB - Individual acts of cooperation give rise to dynamic social networks. Traditionally, models for cooperation in structured populations are based on a separation of individual strategies and of population structure. Individuals adopt a strategy-typically cooperation or defection, which determines their behaviour toward their neighbours as defined by an interaction network. Here, we report a behavioural experiment that amalgamates strategies and structure to empirically investigate the dynamics of social networks. The action of paying a cost c to provide a benefit b is represented as a directed link point from the donor to the recipient. Participants can add and/or remove links to up to two recipients in each round. First, we show that dense networks emerge, where individuals are characterized by fairness: they receive to the same extent they provide. More specifically, we investigate how participants use information about the generosity and payoff of others to update their links. It turns out that aversion to payoff inequity was the most consistent update rule: adding links to individuals that are worse off and removing links to individuals that are better off. We then investigate the effect of direct reciprocation, showing that the possibility of direct reciprocation does not increase cooperation as compared to the treatment where participants are totally unaware of who is providing benefits to them. PMID- 26824241 TI - The Communication of Culturally Dominant Modes of Attention from Parents to Children: A Comparison of Canadian and Japanese Parent-Child Conversations during a Joint Scene Description Task. AB - Previous findings have indicated that, when presented with visual information, North American undergraduate students selectively attend to focal objects, whereas East Asian undergraduate students are more sensitive to background information. However, little is known about how these differences are driven by culture and socialization processes. In this study, two experiments investigated how young children and their parents used culturally unique modes of attention (selective vs. context sensitive attention). We expected that children would slowly learn culturally unique modes of attention, and the experience of communicating with their parents would aid the development of such modes of attention. Study 1 tested children's solitary performance by examining Canadian and Japanese children's (4-6 vs. 7-9 years old) modes of attention during a scene description task, whereby children watched short animations by themselves and then described their observations. The results confirmed that children did not demonstrate significant cross-cultural differences in attention during the scene description task while working independently, although results did show rudimentary signs of culturally unique modes of attention in this task scenario by age 9. Study 2 examined parent-child (4-6 and 7-9 years old) dyads using the same task. The results indicated that parents communicated to their children differently across cultures, replicating attentional differences among undergraduate students in previous cross-cultural studies. Study 2 also demonstrated that children's culturally unique description styles increased significantly with age. The descriptions made by the older group (7-9 years old) showed significant cross-cultural variances in attention, while descriptions among the younger group (4-6 years old) did not. The significance of parental roles in the development of culturally unique modes of attention is discussed in addition to other possible facilitators of this developmental process. PMID- 26824242 TI - Inhibitory Effect of Serotonin Antagonist on Leukocyte-Endothelial Interactions In Vivo and In Vitro. AB - BACKGROUND: Although 5-HT2A serotonergic antagonists have been used to treat vascular disease in patients with diabetes mellitus or obesity, their effects on leukocyte-endothelial interactions have not been fully investigated. In this study, we assessed the effects of sarpogrelate hydrochloride (SRPO), a 5-HT2A receptor inverse agonist, on leukocyte-endothelial cell interactions in obesity both in vivo and in vitro. METHODS AND FINDINGS: In the in vivo experiment, C57BL/6 mice were fed a high-fat high-fructose diet (HFFD), comprising 20% fat and 30% fructose, with or without intraperitoneal injection of 5 mg/kg/day SRPO for 4 weeks. The body weight, visceral fat weight, and serum monocyte chemoattractant protein-1 levels in the mice increased significantly with the HFFD, but these effects were prevented by chronic injections of SRPO. Intravital microscopy of the femoral artery detected significant leukocyte-endothelial interactions after treatment with HFFD, but these leukocyte-endothelial interactions were reduced in the mice injected with SRPO. In the in vitro experiment, pre-incubation of activated human umbilical vein endothelial cells (HUVECs) with platelet-rich plasma (PRP) induced THP-1 cell adhesion under physiological flow conditions, but the adhesion was reduced by pretreatment of PRP with SRPO. A fluorescent immunobinding assay showed that PRP induced significant upregulation of E-selectin in HUVECs, but this upregulation was reduced by pretreatment of PRP with SRPO. In other in vitro conditions, pre incubation of THP-1 cells with phorbol 12-myristate 13-acetate increased the adhesion of THP-1 cells to activated HUVECs under rotational conditions, but this adhesion was reduced by pretreatment with SRPO. Western blotting analysis showed that protein kinase C alpha activation in THP-1 cells was inhibited by SRPO. CONCLUSION: Our findings indicated that SRPO inhibits vascular inflammation in obesity via inactivation of platelets and leukocytes, and improvement of obese. PMID- 26824243 TI - Probing Coagulation Behavior of Individual Aluminum Species for Removing Corresponding Disinfection Byproduct Precursors: The Role of Specific Ultraviolet Absorbance. AB - Coagulation behavior of aluminum chloride and polyaluminum chloride (PACl) for removing corresponding disinfection byproduct (DBP) precursors was discussed in this paper. CHCl3, bromine trihalomethanes (THM-Br), dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) formation potential yields were correlated with specific ultraviolet absorbance (SUVA) values in different molecular weight (MW) fractions of humic substances (HS), respectively. Correlation analyses and principal component analysis were performed to examine the relationships between SUVA and different DBP precursors. To acquire more structural characters of DBP precursors and aluminum speciation, freeze-dried precipitates were analyzed by fourier transform infrared (FTIR) and C 1s, Al 2p X-ray photoelectron spectroscopy (XPS). The results indicated that TCAA precursors (no MW limits), DCAA and CHCl3 precursors in low MW fractions (MW<30 kDa) had a relatively good relations with SUVA values. These DBP precursors were coagulated more easily by in situ Al13 of AlCl3 at pH 5.0. Due to relatively low aromatic content and more aliphatic structures, THM-Br precursors (no MW limits) and CHCl3 precursors in high MW fractions (MW>30 kDa) were preferentially removed by PACl coagulation with preformed Al13 species at pH 5.0. Additionally, for DCAA precursors in high MW fractions (MW>30 kDa) with relatively low aromatic content and more carboxylic structures, the greatest removal occurred at pH 6.0 through PACl coagulation with aggregated Al13 species. PMID- 26824244 TI - DNA Repair Gene (XRCC1) Polymorphism (Arg399Gln) Associated with Schizophrenia in South Indian Population: A Genotypic and Molecular Dynamics Study. AB - This paper depicts the first report from an Indian population on the association between the variant Arg399Gln of XRCC1 locus in the DNA repair system and schizophrenia, the debilitating disease that affects 1% of the world population. Genotypic analysis of a total of 523 subjects (260 patients and 263 controls) revealed an overwhelming presence of Gln399Gln in the case subjects against the controls (P < 0.0068), indicating significant level of association of this nsSNP with schizophrenia; the Gln399 allele frequency was also perceptibly more in cases than in controls (p < 0.003; OR = 1.448). The results of the genotypic studies were further validated using pathogenicity and stability prediction analysis employing computational tools [I-Mutant Suite, iStable, PolyPhen2, SNAP, and PROVEAN], with a view toassess the magnitude of deleteriousness of the mutation. The pathogenicity analysis reveals that the nsSNP could be deleterious inasmuch as it could affect the functionality of the gene, and interfere with protein function. Molecular dynamics simulation of 60ns was performed using GROMACS to analyse structural change due to a mutation (Arg399Gln) that was never examined before. RMSD, RMSF, hydrogen bonds, radius of gyration and SASA analysis showedthe existence of asignificant difference between the native and the mutant protein. The present study gives astrong indication that the XRCC1 locus deserves serious attention, as it could be a potential candidatecontributing to the etio pathogenesis of the disease. PMID- 26824245 TI - The Impact of Menstrual Cycle Phase on Economic Choice and Rationality. AB - It is well known that hormones affect both brain and behavior, but less is known about the extent to which hormones affect economic decision-making. Numerous studies demonstrate gender differences in attitudes to risk and loss in financial decision-making, often finding that women are more loss and risk averse than men. It is unclear what drives these effects and whether cyclically varying hormonal differences between men and women contribute to differences in economic preferences. We focus here on how economic rationality and preferences change as a function of menstrual cycle phase in women. We tested adherence to the Generalized Axiom of Revealed Preference (GARP), the standard test of economic rationality. If choices satisfy GARP then there exists a well-behaved utility function that the subject's decisions maximize. We also examined whether risk attitudes and loss aversion change as a function of cycle phase. We found that, despite large fluctuations in hormone levels, women are as technically rational in their choice behavior as their male counterparts at all phases of the menstrual cycle. However, women are more likely to choose risky options that can lead to potential losses while ovulating; during ovulation women are less loss averse than men and therefore more economically rational than men in this regard. These findings may have market-level implications: ovulating women more effectively maximize expected value than do other groups. PMID- 26824246 TI - ABA Is Required for Plant Acclimation to a Combination of Salt and Heat Stress. AB - Abiotic stresses such as drought, heat or salinity are a major cause of yield loss worldwide. Recent studies revealed that the acclimation of plants to a combination of different environmental stresses is unique and cannot be directly deduced from studying the response of plants to each of the different stresses applied individually. Here we report on the response of Arabidopsis thaliana to a combination of salt and heat stress using transcriptome analysis, physiological measurements and mutants deficient in abscisic acid, salicylic acid, jasmonic acid or ethylene signaling. Arabidopsis plants were found to be more susceptible to a combination of salt and heat stress compared to each of the different stresses applied individually. The stress combination resulted in a higher ratio of Na+/K+ in leaves and caused the enhanced expression of 699 transcripts unique to the stress combination. Interestingly, many of the transcripts that specifically accumulated in plants in response to the salt and heat stress combination were associated with the plant hormone abscisic acid. In accordance with this finding, mutants deficient in abscisic acid metabolism and signaling were found to be more susceptible to a combination of salt and heat stress than wild type plants. Our study highlights the important role abscisic acid plays in the acclimation of plants to a combination of two different abiotic stresses. PMID- 26824248 TI - Lead Sources to the Amundsen Sea, West Antarctica. AB - The global prevalence of industrial lead (Pb) contamination was exemplified decades ago by the predominance of anthropogenic Pb in samples of Antarctic surface ice and in Southern Ocean surface waters. Decreases in environmental Pb contamination corresponding with the near-global phase-out of leaded automobile gasoline beginning in the 1970s have since been observed. Measurements of Pb concentration in snow and ice core samples from Antarctica show that recent fluxes of industrial Pb to Antarctica have similarly declined. Here, we present measurements of Pb concentrations and isotopic compositions in seawater and surface sediments from the Amundsen Sea continental shelf including the Amundsen Sea Polynya. Both sets of measurements show that most (~60-95%) of the Pb at our sites, at the time of sampling, is natural in source: that is, derived from the weathering of Antarctic continental rocks. These fluxes of natural Pb then become entrained into polynya waters either from sediment resuspension or from the transport of sediment-laden glacial melt waters to the polynya. PMID- 26824249 TI - Facile Insertion of Rh and Ir into a Boron-Phenyl Bond, Leading to Boryl/Bis(phosphine) PBP Pincer Complexes. AB - The unexpectedly facile insertion of Rh or Ir into a B-Ph bond (reversible for Rh) converts a borane/bis(phosphine) precursor into a boryl/bis(phosphine) PBP pincer ligand. Interconversions between the boryl/borane/borate central functionality are demonstrated in reactions with dihydrogen. PMID- 26824247 TI - A New Immunoassay for Detecting All Subtypes of Shiga Toxins Produced by Shiga Toxin-Producing E. coli in Ground Beef. AB - BACKGROUND: Shiga toxin (Stx) is a common virulence factor of all Shiga toxin producing E. coli (STEC) that cause a wide spectrum of disease, including hemorrhagic colitis and hemolytic uremic syndrome (HUS). Although several commercial kits are available for detection of Stx produced by STEC, none of them are capable of recognizing all subtypes of Stxs, which include three subtypes of Stx1 and seven subtypes of Stx2. METHODS AND FINDINGS: New monoclonal and polyclonal antibodies against Stx1 and Stx2 were developed. A universal sandwich ELISA capable of detecting all known subtypes of Stx1 and Stx2 was established using a pool of newly developed antibodies. To precisely monitor the sensitivity of the assay for each subtype of Stxs, recombinant toxoids were created and used as standards in ELISAs. Because of the high affinity of the antibodies incorporated, the ELISA assay is highly sensitive with a limit of detection for the different subtypes of Stx1a and Stx2a between 10 and 50 pg/mL in phosphate buffered saline (PBS). The assay was also able to identify STEC based on the production of Stxs using the supernatants of culture fluids or even single colonies on agar plates without lengthy enrichment in liquid medium. When applied to ground beef samples, this newly developed ELISA was capable of distinguishing beef samples spiked with a single bacterial cell. CONCLUSIONS: A highly sensitive and universal assay for all subtypes of Stx1 and Stx2 was developed. It has significantly improved upon the current technologies by avoiding false negative results due to the narrow detection range of the assay. The assay developed in this study can be useful for prompt detection of new and emerging serotypes and screening ground beef samples for contamination of STEC at an early stage in the food supply chain, thus avoiding the need for possible recall. PMID- 26824250 TI - Two-Compartment Kinetic Modeling of Radiocesium Accumulation in Marine Bivalves under Hypothetical Exposure Regimes. AB - Interpreting the variable concentrations of (137)Cs in the field biological samples requires mechanistic understanding of both environmental and biological behavior of (137)Cs. In this study, we used a two-compartment model to estimate and compare the (137)Cs biokinetics in three species of subtropical marine bivalves. Significant interspecific difference of (137)Cs biokinetics was observed among oysters, mussels, and scallops. There was considerable (137)Cs assimilation from phytoplankton in the bivalves, but the calculated trophic transfer factors were generally between 0.04 and 0.4. We demonstrated a major efflux of radiocesium in the scallops (with a rate constant of 0.207 d(-1)), whereas the efflux was comparable between oysters and mussels (0.035-0.038 d( 1)). A two-compartment kinetic model was developed to simulate the (137)Cs accumulation in the three bivalves under four hypothetical exposure regimes. We showed that the bivalves respond differently to the exposure regimes in terms of time to reach equilibrium, equilibrium concentration, and maximum concentration. Bivalves suffering more frequent intermittent exposure may have higher maximum concentrations than those receiving less frequent exposure. The interspecific difference of (137)Cs accumulation in bivalves has important implications for biomonitoring and implementing management techniques. This study represents one of the first attempts to combine both dissolved and dietary pathways to give a realistic simulation of (137)Cs accumulation in marine bivalves under dynamic exposure regimes. PMID- 26824251 TI - Modeling the Influence of Fatty Acid Incorporation on Mesophase Formation in Amphiphilic Therapeutic Delivery Systems. AB - Dispersed amphiphile-fatty acid systems are of great interest in drug delivery and gene therapies because of their potential for triggered release of their payload. The mesophase behavior of these systems is extremely complex and is affected by environmental factors such as drug loading, percentage and nature of incorporated fatty acids, temperature, pH, and so forth. It is important to study phase behavior of amphiphilic materials as the mesophases directly influence the release rate of the incorporated drugs. We describe a robust machine learning method for predicting the phase behavior of these systems. We have developed models for each mesophase that simultaneous and reliably model the effects of amphiphile and fatty acid structure, concentration, and temperature and that make accurate predictions of these mesophases for conditions not used to train the models. PMID- 26824253 TI - Correction to "Asymmetric Reduction of tert-Butanesulfinyl Ketimines by N Heterocyclic Carbene Boranes". PMID- 26824252 TI - PdNP Decoration of Halloysite Lumen via Selective Grafting of Ionic Liquid onto the Aluminol Surfaces and Catalytic Application. AB - The synthesis of selectively deposited palladium nanoparticles (PdNPs) inside tubular halloysite lumens is reported. This specific localization was directed by the selective modification of the aluminol surfaces of the clay mineral through stable Al-O-C bonds. An ionic liquid (1-(2-hydroxyethyl)-3-methylimidazolium) was grafted onto halloysite following the guest displacement method (generally used for kaolinite) using halloysite-DMSO preintercalate. The characterization of this clay nanohybrid material (XRD, NMR, TGA) showed characteristics reminiscent of similar materials synthesized from kaolinite. The grafting on halloysite lumens was also effective without using the DMSO preintercalate. The presence of these new functionalities in halloysite directs the synthesis of uniform PdNPs with size ranging between 3 and 6 nm located exclusively in the lumens. This results from the selective adsorption of PdNPs precursors in functionalized lumens through an anion exchange mechanism followed by in situ reduction. In contrast, the unmodified clay mineral displayed nanoparticles both inside and outside the tubes. These catalysts showed significant catalytic activity for the reduction of 4-nitrophenol (4-NP). The most efficient catalysts were recycled up to three times without reducing significantly the catalytic activities. PMID- 26824254 TI - SERS Amplification from Self-Organized Arrays of Plasmonic Nanocrescents. AB - We report on the surface-enhanced Raman scattering (SERS) efficiency of self organized arrays of Au nanocrescents confined on monolayers of polystyrene nanospheres. A dichroic SERS emission in the visible spectrum is observed due to the selective excitation of a localized surface plasmon (LSP) resonance along the "short axis" of the Au nanocrescents. Under these conditions SERS signal amplifications in the range of 10(3) have been observed with respect to a flat reference Au film. The far field and near field plasmonic response of Au nanocrescent arrays have been investigated as a function of the metal dose deposited onto the polymeric spheres. In this way, we show the possibility of simply tailoring the SERS emission by engineering the morphology of the plasmonic nanocrescents. We highlight the SERS activity of chains of satellite nanoclusters that decorate the border of each connected crescent and sustain isotropic high energy LSP resonances in the visible spectrum. PMID- 26824255 TI - Crystal and Magnetic Structures of the Oxide Sulfides CaCoSO and BaCoSO. AB - CaCoSO, synthesized from CaO, Co, and S at 900 degrees C, is isostructural with CaZnSO and CaFeSO. The structure is non-centrosymmetric by virtue of the arrangement of the vertex-sharing CoS3O tetrahedra which are linked by their sulfide vertices to form layers. The crystal structure adopts space group P63mc (No. 186), and the lattice parameters are a = 3.7524(9) A and c = 11.138(3) A at room temperature with two formula units in the unit cell. The compound is highly insulating, and powder neutron diffraction measurements reveal long-range antiferromagnetic order with a propagation vector k = (1/3, 1/3, 1/2). The magnetic scattering from a powder sample can be modeled starting from a 120 degrees arrangement of Co(2+) spin vectors in the triangular planes and then applying a canting out of the planes which can be modeled in the magnetic space group C(c)c (space group 9.40 in the Belov, Neronova, and Smirnova (BNS) scheme) with Co(2+) moments of 2.72(5) MU(B). The antiferromagnetic structure of the recently reported compound BaCoSO, which has a very different crystal structure from CaCoSO, is also described, and this magnetic structure and the magnitude of the ordered moment (2.75(2) MU(B)) are found by experiment to be similar to those predicted computationally. PMID- 26824256 TI - Barriers to Effective Implementation of Programs for the Prevention of Workplace Violence in Hospitals. AB - Effective workplace violence (WPV) prevention programs are essential, yet challenging to implement in healthcare. The aim of this study was to identify major barriers to implementation of effective violence prevention programs. After reviewing the related literature, the authors describe their research methods and analysis and report the following seven themes as major barriers to effective implementation of workplace violence programs: a lack of action despite reporting; varying perceptions of violence; bullying; profit-driven management models; lack of management accountability; a focus on customer service; and weak social service and law enforcement approaches to mentally ill patients. The authors discuss their findings in light of previous studies and experiences and offer suggestions for decreasing WPV in healthcare settings. They conclude that although many of these challenges to effective implementation of workplace violence programs are both within the program itself and relate to broader industry and societal issues, creative innovations can address these issues and improve WPV prevention programs. PMID- 26824257 TI - Informatics: The Standardized Nursing Terminologies: A National Survey of Nurses' Experience and Attitudes--SURVEY II: Participants' Perception of the Helpfulness of Standardized Nursing Terminologies in Clinical Care. PMID- 26824258 TI - Legislative: Transitioning the Older Adolescent Living with Autism Spectrum Disorder to Adult Primary Medical Home: A Call for Nursing Action. PMID- 26824259 TI - The 2014 Scope and Standards of Practice for Psychiatric Mental Health Nursing: Key Updates. AB - The 2014 Psychiatric-Mental Health Nursing: Scope and Standards of Practice is the specialty's description of competent nursing practice. The scope portion of this document identifies the focus of the specialty by defining nursing practice extents and limits. Standards are statements that identify the duties and obligations for which specialty nurses are held accountable, including general registered nurses and advanced practice nurses. This article begins with a brief overview of the revision process. The author describes key factors that influenced the revision, such as external documents and current priorities in healthcare, and synthesizes significant changes to the document, including commentary and comparisons to the generalist Scope and Standards of Practice. Implications for nursing education and a companion resource are discussed. PMID- 26824260 TI - Suicide Assessment and Nurses: What Does the Evidence Show? AB - Suicide is at epidemic proportions both in the United States and across the globe. Yet, it is a preventable public health problem. Nurses practice on the front-lines and have the greatest number of opportunities to identify and intervene with suicidal patients. Most registered nurses (RNs) have little or no training in how to assess, evaluate, treat, or refer a suicidal patient. Because of this lack of training, RNs feel ill-prepared and afraid to talk to patients about suicide. The purpose of this article is to review the state of the science of suicide assessment training for nurses. Training RNs in how to assess, evaluate, treat, and refer a suicidal patient is key to suicide prevention. Research suggests that once RNs are trained in suicide assessment, they realize it is no different than assessing for any other type of illness and are then able to help those with suicidal tendencies. The article conclusion offers implications for education, research, and practice. PMID- 26824261 TI - Mental Illness and Prisoners: Concerns for Communities and Healthcare Providers. AB - The United States prison system is the largest in the world. Mental illness is disproportionately represented within this system where half of all incarcerated individuals have a mental illness, compared to 11% of the population. Four of 10 inmates released from prison recidivate and are re-incarcerated within three years. A social hypothesis suggests recidivism is the result of compounding social factors. Mentally ill individuals often find themselves in less than ideal circumstances of compounding social factors such as illicit substances and unemployment. Prison life may provide improved social situations and a rehabilitating environment, yet corrections often fall short of meeting acceptable standards of healthcare. This article provides a brief overview of healthcare in the corrections environment and discusses factors that affect mental healthcare in prisons, such as characteristics of the prison population and social policy. The article also addresses factors impacting mentally ill persons who are incarcerated, including access and barriers to mental health treatment and efforts to reduce recidivism. PMID- 26824262 TI - Military Culture Implications for Mental Health and Nursing Care. AB - With over 13 years of war and military combat operations, the number of veterans, military families, and service members with mental health needs continues to increase across civilian and federal healthcare services. Knowledge about severe battle wounds, traumatic brain injury, and traumatic stress has influenced the delivery of healthcare. The invisible wounds of war associated with brain injury and traumatic stress will increase clinical care challenges into the foreseeable future. The purpose of this article is to describe two interrelated concepts, military cultural competence and stress injuries. The authors also differentiate stress reactions versus stress injury. Nurses with military cultural competence and knowledge about stress injuries will be better able to deliver patient centered care to patients with military culture experiences. PMID- 26824263 TI - Positive Mental Health Outcomes in Individuals with Dementia: The Essential Role of Cultural Competence. AB - Over five million people in the United States are diagnosed with some form of dementia, and many more with cognitive impairment remain undiagnosed. In addition, most individuals with dementia experience one or more neuropsychiatric symptoms such as depression, anxiety, irritability, agitation, hallucinations, or delusions at some point during disease progression. The vast majority of individuals with dementia, including those with symptoms of serious mental illness, are cared for in home and community based settings by unpaid caregivers, often family members, who struggle with the daily challenges of providing care and services to someone with dementia. This article will briefly review selected aspects of the need for community care for individuals with dementia and cultural aspects related to dementia and mental health. A detailed case study will illustrate some of the challenges related to the mental health of individuals with dementia living in the community. We specifically discuss culturally competent care, using the example of a Nepalese refugee family caring for a family member with dementia and depression, as a critical aspect of the care plan. Finally, we provide implications for practice for organizations wishing to engage families in a comprehensive system of home-based dementia care. PMID- 26824264 TI - Nurses with Undiagnosed Hearing Loss: Implications for Practice. AB - Hearing loss affects 36 million people in the United States of America, including 17% of the adult population. This suggests some nurses will have hearing losses that affect their communication skills and their ability to perform auscultation assessments, potentially compromising patient care and safety. In this article, the authors begin by reviewing the hearing process, describing various types of hearing loss, and discussing noise-induced hearing loss and noise levels in hospitals. Next, they consider the role of hearing in nursing practice, review resources for hearing-impaired nurses, identify the many costs associated with untreated hearing loss, and note nurses' responsibility for maintaining their hearing health. The authors conclude that nurses need to be aware of their risk for hearing loss and have their hearing screened every five years. PMID- 26824265 TI - Ethics: Employer-Sponsored Wellness Programs for Nurses: The Ethics of Carrots and Sticks. PMID- 26824267 TI - Describing Total Population Health: A Review and Critique of Existing Units. AB - Total population health is a key tenet of health care reform efforts, evident in initiatives such as the National Quality Strategy, shifts toward population-based payments, and community benefit requirements for tax-exempt hospitals. Representing total population health in a way that guides best practices and establishes shared accountability for geographic communities, however, remains a challenge in part because of differences in how stakeholders define populations. To better understand the landscape of potential denominators for population health, this study examined a selection of relevant geographic units. The approach included a comprehensive review of health services and public health research literature as well as recent pertinent health policy documents. Units were characterized based on whether they: exhibit "breadth" of coverage across the whole US population; are "accurate" or grounded in health care utilization patterns; are "actionable" with mechanisms for implementing funding and regulation; and promote "synergism" or effective coordination of public health and health care activities. Although other key components of a total population health unit may exist and no single identified unit possesses all of the aforementioned features, several promising candidates were identified. Specifically, healthcare coalitions link health care and public health domains to care for a geographic community, but their connection to utilization is not empiric and limited funding exists at the coalition level. Although Accountable Care Organizations do not uniformly incorporate public health or facilitate coordination across all payers or providers, they represent an effective mechanism to increase collaboration within health care systems and represent a potential building block to influence total population health. PMID- 26824268 TI - An Albumin-Free Formulation for Escherichia coli-Derived Interferon Beta-1b with Decreased Immunogenicity in Immune Tolerant Mice. AB - Human serum albumin (HSA)-free formulation of Escherichia coli-derived human interferon beta (IFNbeta-1b) with a high percentage of monomeric protein and low immunogenicity is developed and characterized in the current study. UV spectroscopy, fluorescence spectroscopy, dynamic light scattering, sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blotting, Micro-Flow Imaging, resonant mass measurement, size exclusion, and reversed-phase high performance liquid chromatographies were applied to assess the effect of excipients on the stability of IFNbeta-1b to establish a HSA-free formulation. The antiviral activity of IFNbeta-1b was evaluated using human lung carcinoma cell line. Immune tolerant mice to hIFNbeta were used to assess the immunogenicity of the HSA-free formulated IFNbeta-1b in comparison to Betaferon drug product and Avonex drug substance as standards through IgG titering of plasma. HSA-free formulated IFNbeta-1b, including 200 mM L-arginine, 200 mM trehalose, and 0.1% n-dodecyl beta-D-maltoside in 10 mM sodium acetate buffer, pH 7.4, showed the highest biological activity. The stability of IFNbeta-1b in the HSA-free formulation was monitored for 3 weeks at 4 degrees C and 37 degrees C with relative humidity of 10% and 75%, respectively. Protein aggregation and immunogenicity in transgenic mice were decreased in the HSA-free formulated IFNbeta-1b compared to Betaferon. The stability, biological activity, and immunogenicity of the HSA-free formulation and Betaferon were evaluated. Incubation of formulations at 4 degrees C and 37 degrees C for 3 weeks showed that the HSA-free formulated IFNbeta-1b was more stable and less immunogenic in transgenic FVB/N mice. Low immunogenicity and the absence of HSA, which reduces the potential risk of viral infection (eg, HIV and HCV), are promising for clinical studies. PMID- 26824269 TI - Impact of adjacent land use on coastal wetland sediments. AB - Coastal wetlands link terrestrial with marine ecosystems and are influenced from both land and sea. Therefore, they are ecotones with strong biogeochemical gradients. We analyzed sediment characteristics including macronutrients (C, N, P, K, Mg, Ca, S) and heavy metals (Mn, Fe, Cu, Zn, Al, Co, Cr, Ni) of two coastal wetlands dominated by Phragmites australis at the Darss-Zingst Bodden Chain, a lagoon system at the Southern Baltic Sea, to identify the impact of adjacent land use and to distinguish between influences from land or sea. In the wetland directly adjacent to cropland (study site Dabitz) heavy metal concentrations were significantly elevated. Fertilizer application led to heavy metal accumulation in the sediments of the adjacent wetland zones. In contrast, at the other study site (Michaelsdorf), where the hinterland has been used as pasture, heavy metal concentrations were low. While the amount of macronutrients was also influenced by vegetation characteristics (e.g. carbon) or water chemistry (e.g. sulfate), the accumulation of heavy metals is regarded as purely anthropogenic influence. A principal component analysis (PCA) based on the sediment data showed that the wetland fringes of the two study sites are not distinguishable, neither in their macronutrient status nor in their concentrations of heavy metals, whereas the interior zones exhibit large differences in terms of heavy metal concentrations. This suggests that seaside influences are minor compared to influences from land. Altogether, heavy metal concentrations were still below national precautionary and action values. However, if we regard the macronutrient and heavy metal concentrations in the wetland fringes as the natural background values, an accumulation of trace elements from agricultural production in the hinterland is apparent. Thus, coastal wetlands bordering croplands may function as effective pollutant buffers today, but the future development has to be monitored closely to avoid breakthroughs due to exceeded carrying capacities. PMID- 26824270 TI - Multi-level multi-criteria analysis of alternative fuels for waste collection vehicles in the United States. AB - Historically, the U.S. waste collection fleet was dominated by diesel-fueled waste collection vehicles (WCVs); the growing need for sustainable waste collection has urged decision makers to incorporate economically efficient alternative fuels, while mitigating environmental impacts. The pros and cons of alternative fuels complicate the decisions making process, calling for a comprehensive study that assesses the multiple factors involved. Multi-criteria decision analysis (MCDA) methods allow decision makers to select the best alternatives with respect to selection criteria. In this study, two MCDA methods, Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) and Simple Additive Weighting (SAW), were used to rank fuel alternatives for the U.S. waste collection industry with respect to a multi-level environmental and financial decision matrix. The environmental criteria consisted of life-cycle emissions, tail-pipe emissions, water footprint (WFP), and power density, while the financial criteria comprised of vehicle cost, fuel price, fuel price stability, and fueling station availability. The overall analysis showed that conventional diesel is still the best option, followed by hydraulic-hybrid WCVs, landfill gas (LFG) sourced natural gas, fossil natural gas, and biodiesel. The elimination of the WFP and power density criteria from the environmental criteria ranked biodiesel 100 (BD100) as an environmentally better alternative compared to other fossil fuels (diesel and natural gas). This result showed that considering the WFP and power density as environmental criteria can make a difference in the decision process. The elimination of the fueling station and fuel price stability criteria from the decision matrix ranked fossil natural gas second after LFG sourced natural gas. This scenario was found to represent the status quo of the waste collection industry. A sensitivity analysis for the status quo scenario showed the overall ranking of diesel and fossil natural gas to be more sensitive to changing fuel prices as compared to other alternatives. PMID- 26824266 TI - TGFbeta-dependent expression of PD-1 and PD-L1 controls CD8(+) T cell anergy in transplant tolerance. AB - CD8(+) T cell anergy is a critical mechanism of peripheral tolerance, poorly investigated in response to immunotherapy. Here, using a pancreatic islet allograft model and CD3 antibody therapy, we showed, by single cell gene profiling, that intragraft CD8(+) lymphocytes coexpressing granzyme B and perforin were selectively depleted through the Fas/FasL pathway. This step led to long-standing anergy of the remaining CD8(+) T cells marked by the absence of cytotoxic/inflammatory gene expression also confirmed by transcriptome analysis. This sustained unresponsiveness required the presence of the alloantigens. Furthermore, tissue-resident CD8(+) lymphocytes produced TGFbeta and expressed the inhibitory receptors PD-1 and PD-L1. Blockade of TGFbeta downregulated PD-1 and PD-L1 expression and precipitated graft rejection. Neutralizing PD-1, PD-L1 or TGFbetaRII signaling in T cells also abrogated CD3 antibody-induced tolerance. These studies unravel novel mechanisms underlying CD8(+) T cell anergy and reveal a cell intrinsic regulatory link between the TGFbeta and the PD-1/PD-L1 pathways. PMID- 26824271 TI - Amelioration of bauxite residue sand by intermittent additions of nitrogen fertiliser and leaching fractions: The effect on growth of kikuyu grass and fate of applied nutrients. AB - Bauxite residue, a waste product of aluminium processing operations is characterised by high pH, salinity and exchangeable sodium which hinders sustainable plant growth. The aim of this study was to investigate the uptake form, optimum application rate and timing of nitrogen fertiliser to improve bauxite residue characteristics for plant growth. Kikuyu grass was grown in plastic columns filled with residue sand/carbonated residue mud mixture (20:1) previously amended with gypsum, phosphoric acid and basal nutrients. The experiment was set up as a 4*4 factorial design comprising four levels of applied nitrogen (N) fertiliser (0, 3, 6 and 12mgNkg(-1) residue) and four frequencies of leaching (16, 8 and 4day intervals). We hypothesised that the use of ammonium sulfate fertiliser would increase retention of N within the rhizosphere thereby encouraging more efficient fertiliser use. We found that N uptake by kikuyu grass was enhanced due to leaching of excess salts and alkalinity from the residue profile. It was also concluded that biomass production and associated N uptake by kikuyu grass grown in residue is dependent on the type of fertiliser used. PMID- 26824272 TI - Identification of Pseudomonas aeruginosa and Aspergillus fumigatus mono- and co cultures based on volatile biomarker combinations. AB - Volatile organic compound (VOC) analysis in exhaled breath is proposed as a non invasive method to detect respiratory infections in cystic fibrosis patients. Since polymicrobial infections are common, we assessed whether we could distinguish Pseudomonas aeruginosa and Aspergillus fumigatus mono- and co cultures using the VOC emissions. We took headspace samples of P. aeruginosa, A. fumigatus and co-cultures at 16, 24 and 48 h after inoculation, in which VOCs were identified by thermal desorption combined with gas chromatography - mass spectrometry. Using multivariate analysis by Partial Least Squares Discriminant Analysis we found distinct VOC biomarker combinations for mono- and co-cultures at each sampling time point, showing that there is an interaction between the two pathogens, with P. aeruginosa dominating the co-culture at 48 h. Furthermore, time-independent VOC biomarker combinations were also obtained to predict correct identification of P. aeruginosa and A. fumigatus in mono-culture and in co culture. This study shows that the VOC combinations in P. aeruginosa and A. fumigatus co-microbial environment are different from those released by these pathogens in mono-culture. Using advanced data analysis techniques such as PLS DA, time-independent pathogen specific biomarker combinations can be generated that may help to detect mixed respiratory infections in exhaled breath of cystic fibrosis patients. PMID- 26824273 TI - Ability of Measures of Adiposity in Identifying Adverse Levels of Inflammatory and Metabolic Markers in Adolescents. AB - BACKGROUND: Overweight and obesity have been associated with a pro-inflammatory state. We aimed to assess the ability of different measures of overall and abdominal adiposity for identifying adverse levels of inflammatory and metabolic markers in adolescents. METHODS: This is a cross-sectional analysis with 529 Portuguese adolescents (267 girls), mean age 14.3 +/- 1.7 years. Weight, height, sitting height, waist circumference (WC), and body fat percentage (BF%) were measured; and BMI, waist-to-height ratio (WHtR), and waist-to-sitting-height ratio (WsHtR) were calculated. We measured C-reactive protein (CRP), fibrinogen, erythrocyte sedimentation rate (ESR), complements C3 and C4, leptin, and adiponectin levels. Receiver operating characteristic (ROC) curves were used to estimate the ability of the adiposity measures to discriminate between low/high values of biomarkers. RESULTS: The highest areas under the ROC curves were presented by BF% for fibrinogen and complement C3 in both sexes and for ESR, complement C4, and adiponectin only in girls; by BMI for CRP in girls and for leptin in both sexes; by WHtR for leptin in both sexes and for CRP, fibrinogen, and adiponectin only in girls; by waist circumference for CRP, fibrinogen, and complement C3 only in boys and for complement C4 in girls; and by WsHtR for complement C3 in girls; p < 0.05 for all. CONCLUSIONS: The measures that more often presented discriminatory power were, for overall adiposity, BF% in both sexes, and for abdominal adiposity, WHtR in girls and WC in boys. However, small differences in discriminatory capabilities don't allow us to clearly defend the adoption of a single measure above all others. PMID- 26824274 TI - Arsenic (III, V), indium (III), and gallium (III) toxicity to zebrafish embryos using a high-throughput multi-endpoint in vivo developmental and behavioral assay. AB - Gallium arsenide (GaAs), indium gallium arsenide (InGaAs) and other III/V materials are finding increasing application in microelectronic components. The rising demand for III/V-based products is leading to increasing generation of effluents containing ionic species of gallium, indium, and arsenic. The ecotoxicological hazard potential of these streams is unknown. While the toxicology of arsenic is comprehensive, much less is known about the effects of In(III) and Ga(III). The embryonic zebrafish was evaluated for mortality, developmental abnormalities, and photomotor response (PMR) behavior changes associated with exposure to As(III), As(V), Ga(III), and In(III). The As(III) lowest observable effect level (LOEL) for mortality was 500 MUM at 24 and 120 h post fertilization (hpf). As(V) exposure was associated with significant mortality at 63 MUM. The Ga(III)-citrate LOEL was 113 MUM at 24 and 120 hpf. There was no association of significant mortality over the tested range of In(III)-citrate (56-900 MUM) or sodium citrate (213-3400 MUM) exposures. Only As(V) resulted in significant developmental abnormalities with LOEL of 500 MUM. Removal of the chorion prior to As(III) and As(V) exposure was associated with increased incidence of mortality and developmental abnormality suggesting that the chorion may normally attenuate mass uptake of these metals by the embryo. Finally, As(III), As(V), and In(III) caused PMR hypoactivity (49-69% of control PMR) at 900-1000 MUM. Overall, our results represent the first characterization of multidimensional toxicity effects of III/V ions in zebrafish embryos helping to fill a significant knowledge gap, particularly in Ga(III) and In(III) toxicology. PMID- 26824275 TI - Malignancies in transplanted patients: Multidisciplinary evaluation and switch to mTOR inhibitors after kidney transplantation - experiences from a prospective, clinical, observational study. AB - Background Solid organ transplant recipients are at increased risk of developing malignancies. The objective of this prospective, observational, one-armed study was to study the feasibility to add a mammalian target of rapamycin (mTOR) inhibitor to the immunosuppressive regimen in transplanted patients with post transplant malignancies. During the trial the need to improve identification of post-transplant malignancies and to reassure adequate oncological treatment of these patients became evident. Multidisciplinary team (MDT) evaluation of oncological and immunosuppressive treatments was implemented for all patients with malignancies after renal or combined renal and pancreas transplantation because of the trial. Material and methods At Uppsala University Hospital, Sweden, a MDT consisting of transplant surgeons, nephrologists, oncologists and dermatologists evaluated 120 renal or combined renal and pancreas-transplanted recipients diagnosed with malignancies from September 2006 to July 2012. To identify all malignancies, the population was linked to the Regional Tumor Registry (RTR). We recorded to which extent a switch to mTOR inhibitors was possible and how often the originally planned oncological managements were adjusted. All patients were followed for three years. (ClinicalTrials.gov: NCT02241564). Results In 76 of 120 patients (63%) a switch to mTOR inhibitors was possible. Immunosuppression was interrupted in seven patients (6%), reduced in three patients (2%) and remained unchanged in 34 of 120 patients (28%). Identification of post-transplant malignancies increased significantly after linkage to RTR (p = 0.015). The initially recommended oncological treatment was adjusted in 23 of 44 patients (52%) with solid or hematological malignancies; 36 of these patients (82%) were treated according to national guidelines. Conclusion In two thirds of the patients the immunosuppressive treatment could be changed to an mTOR inhibitor with anti-tumor effects in transplanted patients with post transplant malignancies. The use of regional tumor registers considerably improved the identification of patients with post-transplant malignancies indicating that post-transplant malignancies might be timely underreported in transplant registers. PMID- 26824276 TI - Decreased expression of heme oxygenase is associated with depressive symptoms and may contribute to depressive and hypertensive comorbidity. AB - BACKGROUND: There is strong evidence that hypertension and depression are comorbid and oxidative stress is implicated in both pathologies. We aimed to elucidate the relationship between biochemical markers of the antioxidant-pro oxidant equilibrium and depression in hypertension. METHODS: Blood was collected from patients diagnosed with depression, hypertension, or comorbid depression and hypertension and healthy age- and sex-matched controls. Whole blood reduced glutathione, erythrocyte superoxide dismutase (SOD-1), glutathione peroxidase (GPx-1), glutathione reductase (GR), malondialdehyde (MDA), and plasma hydrogen peroxide (H2O2) were assayed using spectrophotometry, and heme oxygenase (HO-1) levels were determined immunoenzymatically. RESULTS: Both hypertension and depression were associated with altered antioxidant-pro-oxidant profiles. Decreased GPx-1 and SOD-1 activities, increased GR activity, increased levels of GSH, and increased concentrations of MDA and H2O2 were observed in patients compared to controls. Inducible HO-1 was specifically decreased in patients with depression and was significantly associated with both the prevalence and severity of depressive symptoms. CONCLUSIONS: Heme oxygenase is a biological factor that might explain the relationship between inflammation, oxidative stress, and the biological and functional changes in brain activity in depression. HO-1 is a candidate depression biomarker and provides an avenue for novel preventative and diagnostic strategies against this disease. PMID- 26824277 TI - SAR studies on FXR modulators led to the discovery of the first combined FXR antagonistic/TGR5 agonistic compound. AB - BACKGROUND: Bile acids can serve as signaling molecules by activating the nuclear receptor FXR and the G-protein-coupled receptor TGR5 and both bile acid receptors are prominent experimental drug targets. Results/methodology: In this study we optimized the fatty acid mimetic compound pirinixic acid to a new scaffold with the aim to develop novel FXR modulatory compounds. After a multistep structure activity optimization process, we discovered FXR agonistic compounds and the first dual FXR antagonistic and TGR5 agonistic compound 79a. CONCLUSION: With this novel dual activity profile on both bile acid receptors 79a might be a valuable pharmalogical tool to further study the bile acid signaling network. PMID- 26824278 TI - Uptake Pathway, Translocation, and Isomerization of Hexabromocyclododecane Diastereoisomers by Wheat in Closed Chambers. AB - To study the uptake pathways of 3 main hexabromocyclododecane diastereoisomers (alpha-, beta-, and gamma-HBCDs) in wheat, four closed chambers were designed to expose wheat to HBCDs via air and/or soil for 4 weeks. The results showed that HBCDs could be absorbed by wheat both via root from soil and via leaf from air. The Rt values (ratio of HBCDs from root-to-leaf translocation to the total accumulation in leaves) ranging from 14.4 to 29.8% suggested that acropetal translocation within wheat was limited. A negative linear relationship was found between log Rt and log Kow of the HBCD diastereoisomers (p < 0.05). The bioconcentration factors (BCFs, (MUg/g wheat tissues)/(MUg/g soil)) were in the order alpha- > beta- > gamma-HBCD in wheat roots and stems, being negatively related to their Kow values. No such correlation was found in leaves, where the HBCDs came mainly from air distribution. The results of enantiomeric fractions indicated that the (-)-enantiomer of alpha- and gamma-HBCDs and the (+)-beta enantiomer were selectively accumulated. Furthermore, beta- and gamma-HBCDs were transformed to alpha-HBCD in the wheat, with 0.309-4.80% and 0.920-8.40% bioisomerization efficiencies at the end of the experiment, respectively, being the highest in leaves. Additionally, no isomerization product from alpha-HBCD was found. PMID- 26824279 TI - Potent inhibition of cyclic diadenylate monophosphate cyclase by the antiparasitic drug, suramin. AB - C-di-AMP synthases are essential in several bacteria, including human pathogens; hence these enzymes are potential antibiotic targets. However, there is a dearth of small molecule inhibitors of c-di-AMP metabolism enzymes. Screening of 2000 known drugs against DisA has led to the identification of suramin, an antiparasitic drug as potent inhibitor of c-di-AMP synthase. PMID- 26824281 TI - Fasting C-peptide and Related Parameters Characterizing Insulin Secretory Capacity for Correctly Classifying Diabetes Type and for Predicting Insulin Requirement in Patients with Type 2 Diabetes. AB - BACKGROUND/AIMS: C-peptide allows estimation of insulin secretion even in the presence of insulin treatment. C-peptide may be suitable for the differential diagnosis of type 1 and type 2 diabetes, and, within type 2 diabetes, of insulin requiring vs. non-insulin-requiring patients. Relating C-peptide concentrations to ambient glucose levels might improve its diagnostic potential. PATIENTS/METHODS: The diagnostic value (a) fasting C-peptide, (b) C peptide/glucose ratios, and (c) the HOMA-betaC-peptide-index for predicting a diagnosis of type 1 (vs. type 2) diabetes were assessed. SETTING: Specialised hospital for the care of diabetic patients (inpatient treatment). 303 patients with type 1 diabetes and 841 patients with type 2 diabetes. MAIN OUTCOME MEASURE: Odds ratios and 95% confidence intervals for a clinical diagnosis of type 1 diabetes or for insulin treatment by deciles of (a) fasting C-peptide, (b) C peptide/glucose ratios, and (c) HOMA-betaC-peptide-index. RESULTS: Low C-peptide concentrations were associated with a high odds ratio for type 1 diabetes and vice versa (p<0.0001). Concentrations of 0.13-0.36 nmol/l did not discriminate. C peptide/glucose ratios or HOMA-betaC-Peptide did not perform better. The ability of all 3 parameters to predict the necessity for insulin treatment within the population of type 2-diabetic patients was low. CONCLUSIONS: Fasting C-peptide and derived parameters help to differentiate type 1 from type 2 diabetes, but there is a range of C-peptide concentrations that does not help discriminate. Relating C-peptide to glucose did not improve diagnostic accuracy. C-peptide does not help predicting a need for insulin treatment in patients with type 2 diabetes. PMID- 26824280 TI - Effect of Vitamin D Treatment on Serum Sclerostin Level. AB - Objective Sclerostin is an osteocyte-secreted endogenous inhibitor of Wnt signaling. Several systemic and local factors have been suggested as possible regulators of sclerostin expression by osteocytes. In this study, we examined the effect of vitamin D treatment on sclerostin levels. Subject and Methods 44 patients with diagnosis of vitamin D deficiency (25(OH)D<=20 ng/ml) were involved in the study. Patients had monthly intramuscular injection of 300.000 IU cholecalciferol for 3 consecutive months. Sclerostin, 25(OH)D, parathyroid hormone (PTH), calcium, phosphorus and alkaline phosphatase (ALP) levels were measured during the diagnosis and after the replacement of vitamin D. Results 8 male and 36 female patients were enrolled in the study. Minimum age, maximum age and average age were 21, 55 and 32.02+/-9.26 years, respectively. A statistically significant difference was observed between the pre-treatment and post-treatment values in 25(OH)D levels (p:0.001, 10.27+/-4.62 ng/ml and 51.40+/-14.62 ng/ml, respectively), PTH levels (p:0.001, 50.32+/-19.05 pg/ml and 33.97+/-13.12 pg/ml, respectively) and sclerostin levels (p:0.002, 858.98+/-351.63 pg/ml and 689.52+/ 197.92 pg/ml, respectively). No statistically significant difference, however, was found between the pre-treatment and post-treatment calcium, phosphorus and ALP levels. Correlation analysis made on pre-treatment and post-treatment sclerostin levels and 25(OH)D, PTH, calcium, phosphorus and ALP levels revealed no statistically significant correlation. Conclusion Our findings show that the sclerostin level of patients with vitamin D deficiency decreases considerably through treatment. PMID- 26824282 TI - Serum Levels of Copeptin are Decreased in Gestational Diabetes Mellitus. AB - OBJECTIVE: Copeptin, the c-terminal part of pro-Arginine vasopressin, has recently been introduced as a novel risk factor to develop facets of the metabolic syndrome. However, regulation of copeptin in pregnancy-associated metabolic disease, i. e., gestational diabetes mellitus (GDM), has not been fully understood, so far. PATIENTS AND MEASUREMENTS: For this study, 74 GDM patients and 74 healthy, pregnant, age-, body mass index-, and gestational age-matched controls were recruited. Serum levels of copeptin were quantified by an illuminometric assay. Furthermore, copeptin concentrations were correlated to biochemical and anthropometric markers of obesity, glucose and lipid metabolism, renal function, and inflammation. RESULTS: Median [interquartile range] serum copeptin levels were significantly lower in subjects with GDM (3.5 [2.0] pmol/l) as compared to controls (4.4 [3.2] pmol/l) (p<0.05). Furthermore, GDM remained an independent predictor of circulating copeptin in multivariate regression analysis (p<0.05). Moreover, copeptin was independently associated with gestational age at blood sampling (p<0.05). CONCLUSIONS: Copeptin serum levels are significantly lower in GDM as compared to healthy pregnant controls. Further studies are needed to better clarify the pathophysiological role of copeptin in GDM. PMID- 26824283 TI - High Quality of Diabetes Care Based Upon Individualised Treatment Goals - A Cross Sectional Study in 4784 Patients in Germany. AB - OBJECTIVE: Recent guidelines recommend an individualized approach towards patients with diabetes mellitus. Data of a programme dealing with quality of diabetes care, "Diabetes TUV" of the Deutsche BKK was reappraised in the light of recent evidence applying these recommendations. PATIENTS AND METHODS: Data originates from a population-based study in primary diabetes care in Germany. Patients with diabetes mellitus insured by the Deutsche BKK were invited to participate. From 2000 to 2004 data of 4 784 patients participated. Double or multiple visits were not included. HbA1c was analysed in 0.5% categories and in age groups below and above 70 years. HbA1c was DCCT adjusted. RESULTS: A total of 368 patients with diabetes mellitus type 1 (DM1) (42% women, HbA1c 54 mmol/mol (7.1%), BP 136/79 mmHg) and 4 416 patients with diabetes type 2 (DM2) (44% women, HbA1c 48.6 mmol/mol (6.6%), BP 142/81 mmHg) were included.). An HbA1c of 53 mmol/mol (7%) or less was found in 70%, less than 64 mmol/mol (8%) in 87% of all patients, and higher than 86 mmol/mol (10%) in 2.8%. The detailed analysis shows that an HbA1c of <=47.6 mmol/mol (6.5%) is achieved of 38% of people with DM1 and 56% with DM2, an HbA1c <=66 mmol/mol (8.0%) of 79% and 88%, respectively.The mean systolic blood pressure (BP) was 142 mmHg, the diastolic BP was 81 mmHg. Systolic BP increased with age (systolic BP: < 50 years 131 mmHg; 50-70 years 142 mmHg; > 70 years 144 mmHg/diastolic BP: < 50 years 81 mmHg; 50-70 years 82 mmHg; > 70 years 80 mmHg). Using WHO grading, BP is mainly mildly elevated (grade 1: 41% (n=1942); grade 2, 17% (n=820) grade 3 6% (n=281). In 10 patients (0.2%) HbA1c above 86 mmol/mol (10.0%) coincides with a BP WHO grade 3. CONCLUSIONS: In recent years new evidence is available regarding treatment targets. The reappraisal of a cross sectional study of a quality assurance programme of a German health insurance in a differentiated way demonstrates that more than 2/3 of the people with diabetes mellitus meet their specific goals. Only very few patients are at imminent risk due to bad glycaemic control and high blood pressure. Old patients may be at risk of overtreatment. Strategies aiming at adapting pharmacological interventions in older patients must be conceived. PMID- 26824284 TI - The Effect of Simvastatin on Plasma Steroid Hormone Levels in Metformin-Treated Women with Non-Classic Congenital Adrenal Hyperplasia. AB - Non-classic congenital adrenal hyperplasia (NC-CAH), one of the most common genetic disorders, is often associated with the presence of hyperandrogenism. Recently both simvastatin and metformin were found to reduce plasma steroid hormone levels in this disorder. This study included 8 women with NC-CAH and diabetes or impaired glucose tolerance, as well as 12 matched women with similar glucose metabolism abnormalities but normal adrenal function. Both groups of women, receiving metformin for at least 6 months, were then treated with simvastatin (20 mg daily) for the following 12 weeks. Compared to patients with normal adrenal function, metformin-treated women with NC-CAH showed increased plasma levels of 17-hydroxyprogesterone, total testosterone, free testosterone, androstenedione and DHEA-S. Simvastatin reduced total and LDL cholesterol levels in both patients with NC-CAH and normal adrenal function. Moreover, in the former group of women, statin therapy decreased plasma levels of testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulphate and tended to reduce 17-hydroxyprogesterone. Our results suggest that metformin-statin combination therapy may be useful in the management of symptomatic women with NC CAH. PMID- 26824285 TI - 3-Deoxyglucosone Induced Acute Glucose Intolerance in Sprague-Dawley Rats: Involvement of Insulin Resistance and Impaired beta-cell Function. AB - A recent study found an increased level of 3DG during oral glucose load in healthy individuals, which redirects our attention to the effect of high plasma 3DG level in the pathophysiology of type 2 diabetes mellitus. We found previously that abnormally elevated plasma 3DG was significantly associated with the impaired glucose regulation in non-diabetic seniors. The current study aimed to investigate the acute effects of exogenous 3DG on plasma 3DG levels, glucose tolerance and insulin levels. A significant increase in the plasma level of 3DG was observed in rats administrated 50 mg/kg 3DG i. v. even 2 h after. With the acute elevation of circulating 3DG, intravenous glucose tolerance of normal rats was impaired, whereas plasma insulin levels were higher. The 3DG-mediated impairment in glucose tolerance was associated with the attenuated insulin stimulated glucose uptake in the adipose and liver tissues and the decreased glucose-stimulated insulin secretion in the pancreas tissue. In rats treated with 50 mg/kg 3DG i. v., a reduced phosphorylation of p85-PI3K was observed in both the liver and pancreas tissues. The increase in plasma levels of 3DG and the deleterious effects of 3DG were attenuated by aminoguanidine pretreatment. Our results indicated a close association of 3DG with diabetes through participating in inducing acute glucose intolerance involvement of PI3K signaling in healthy individuals. By such a mechanism, a 3DG-targeted intervention to attenuation of the acute elevation of circulating 3DG is promising new therapeutic and prevention strategies for diabetes and its complications. PMID- 26824286 TI - Thyroid Hormone Withdrawal Further Exacerbates Oxidative Stress in Patients with Thyroid Carcinoma. AB - PURPOSE: Hypothyroidism has profound effects on multiple organs and systems including cellular oxidative damage. Thus, we aimed to investigate the effects of acute hypothyroidism on oxidative stress in patients with differentiated thyroid carcinoma (DTC). PATIENTS: 33 patients with DTC were involved in the study. 23 healthy subjects matched for age and body mass index (BMI) served as control group. Fasting blood sample was obtained for the determination of blood chemistry, lipids, myeloperoxidase (MPO) activity, total lipid hydroperoxide (LHP), pyrrolized protein, protein carbonyl compounds (PCC), advanced oxidation protein products (AOPP) and thiol levels before and after thyroid hormone withdrawal (THW) in patients with DTC. RESULTS: MPO activity, total LHP, pyrrolized protein, PCC and AOPP levels were significantly higher, but thiol levels were significantly lower in patients with DTC while on L-thyroxine treatment than those of healthy subjects. At acute hypothyroid status after THW, MPO activity, total LHP, pyrrolized protein, PCC and AOPP levels further increased, thiol levels further decreased in patients with DTC as compared to healthy subjects and to their on L-thyroxine treatment period. CONCLUSIONS: This study showed an increased oxidative stress in patients with DTC which is further exacerbated with acute hypothyroidism upon THW. This situation may have treatment implications such as antioxidant therapy, at least during THW. PMID- 26824287 TI - Intraocular Pressure Changes During Oral Glucose Tolerance Tests in Diabetic and Non-diabetic Individuals. AB - BACKGROUND: Hyperglycaemia in diabetic patients may lead to elevated intraocular pressure. Different reasons have been suggested in previous studies to explain the increase in intraocular pressure. The purpose of the present study was to investigate the change in intraocular pressure during oral glucose tolerance tests in diabetic and non-diabetic subjects. PATIENTS AND METHODS: 51 individuals who fulfilled the inclusion criteria of the study and were scheduled for oral glucose tolerances tests based on the recommendations of World Health Organization (WHO) underwent clinical examinations. Biochemical parameters associated with metabolic syndrome, insulin resistance (HOMA-IR) and systolic and diastolic blood pressure were also measured. A complete ophthalmologic examination was performed before the test. During the test, intraocular pressure was measured twice in the fasting state and at the first and second hours after oral glucose administration using rebound tonometry (ICARE). RESULTS: The mean age of the 51 patients was 46.19+/-9.13 years. The participants were categorized as non-diabetic (n: 24) and diabetic (n: 27). The baseline glucose levels were higher in the diabetic patients (p<0.001). The first-hour intraocular pressures (IOP1-0) changes in the right eye were significant in the diabetic and non diabetic participants, and the first-hour intraocular pressure changes in the left eye (IOP1-0l) in the diabetic group were significant (p=0.017, p=0.017, p<0.001, respectively). CONCLUSION: The relation between diabetes mellitus and glaucoma has been addressed in many studies, but no clear underlying mechanisms have been identified. In our study of diabetic and non-diabetic individuals, hyperglycaemia during an oral glucose tolerance test was found to be positively related to intraocular pressure, which suggests that hyperglycaemia may represent a possible mechanism by which elevated IOP occurs. PMID- 26824288 TI - Effects of Low Intensity Exercise Against Apoptosis and Oxidative Stress in Streptozotocin-induced Diabetic Rat Heart. AB - Background The aim of this study was to investigate the effects of low intensity exercise on heart of streptozotocin (STZ)-induced diabetic rats. Materials and Methods The rats were randomly divided into 3 experimental groups: A (control), B (diabetic untreated), and C (diabetic treated with low intensity exercise); each group contains 8 animals. B and C groups received STZ. Diabetes was induced in 2 groups by a single intraperitoneal (i.p) injection of STZ (40 mg/kg, freshly dissolved in 0,1 M citrate buffer, pH 4.2). 2 days after STZ treatment, diabetes in 2 experimental groups was confirmed by measuring blood glucose levels. Rats with blood glucose levels of 250 mg/dl or higher were considered to be diabetic. Animals in the exercise group were made to run the treadmill once a day for 4 consecutive weeks. Exercise started 3 days prior to STZ administration. Results After induction of diabetes, histological abnormalities were observed, including myofibrillar loss, vacuolization of cytoplasm and irregularity of myofibrils. These alterations were attenuated by low intensity exercise. Our data indicates a significant reduction of oxidative stress and apoptosis in cardiomyocytes after exercise. Treatment of diabetic animals with low intensity exercise, decreased the elevated tissue malondialdehyde (MDA) levels and increased the reduced activities of the enzymatic antioxidants superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in cardiac tissue. Conclusion These findings suggest that low intensity exercise has a therapeutic protective effect in diabetes by decreasing oxidative stress and apoptosis, and by preservation of myocardial integrity. PMID- 26824289 TI - A Preliminary Study to Forecast Japanese Encephalitis Vector Abundance in Paddy Growing Area, with the Aid of Radar Satellite Images. AB - Vector mosquitoes of Japanese encephalitis (JE) breed mostly in rice fields, and human cases occur scattered over extended rural rice-growing areas. From this, one may surmise an ecological connection with the irrigation facilities and paddy cultivation. Furthermore, it has been hypothesized that a particular stage of paddy growth is a premonitory sign that can lead to a markedly increased population of the vector mosquitoes. The present study aimed to forecast the vector abundance by monitoring the paddy growth using remote sensing and geographical information systems. The abundance of the JE vector Culex tritaeniorhynchus peaked when the paddy crop was at its heading stage and dipped when the crop reached the maturing stage. A significant positive correlation was observed between paddy growth and adult density (r = 0.73, p < 0.008). The sigma naught values (sigma0) derived from satellite images of paddy fields ranged from 18.3 (during transplantation stage) to approximately -10 (during the noncultivation period). A significant positive correlation was observed between sigma0 and paddy growth stages (r = 0.87, p < 0.05) and adult vector density (r = 0.74, p = 0.04). The sigma0 value observed during the vegetative and flowering stages of paddy growth ranged from -17.6 to -17.16, at which period the vector density started building up. This could be the spectral signature that denotes the "risk," following which a high vector abundance is expected during heading stage of the paddy. PMID- 26824290 TI - Antiproliferative effect of beta-escin - an in vitro study. AB - This study examined the antiproliferative effects of beta-escin (E) in cancer cells. The study showed that E inhibited cancer cells growth in a dose-dependent manner. The flow cytometric analysis revealed an escin-induced increase in the sub-G1 DNA content, which is considered to be a marker of apoptosis. Apoptosis was also confirmed by annexin V staining and DNA fragmentation assay. These effects were associated with increased generation of reactive oxygen species (ROS), caspase-3 activation and decreased mitochondrial membrane potential (MMP). Moreover, escin decreased mitochondrial protein content and mitochondrial fluorescence intensity as well as caused depletion of glutathione (GSH). However, activity of glutathione peroxidase (GPx) and glutathione reductase (GR) was not significantly changed in escin-treated cells. In conclusion, our results demonstrated that E has apoptotic effects in human cancer cells through the mechanisms involving mitochondrial perturbation. Although the exact mechanism needs to be investigated further, it can be concluded that E may be a useful candidate agent for cancer treatment. PMID- 26824291 TI - The factor VIII protein and its function. AB - Factor VIII (FVIII), an essential blood coagulation protein, is a key component of the fluid phase blood coagulation system. Human factor VIII is a single chain of about 300 kDa consisting of domains described as A1-A2-B-A3-C1-C2. The protein undergoes processing prior to secretion into blood resulting in a heavy chain of 200 kDa (A1-A2-B) and a light chain of 80 kDa (A3-C1-C2) linked by metal ions. The role of factor VIII is to increase the catalytic efficiency of factor IXa in the activation of factor X. Variants of these factors lead frequently also to severe bleeding disorders. PMID- 26824292 TI - Nutritional predictors of mortality in prevalent peritoneal dialysis patients. AB - Malnutrition remains one of the major predictors of mortality in peritoneal dialysis (PD) patients. The aim of the study was to evaluate the nutritional status of prevalent PD patients, and to determine the best predictors of outcome among anthropometric and laboratory indices of nutrition. The study included 106 prevalent PD patients from a single university-based unit. Anthropometric assessment at baseline included: body mass, body mass index (BMI), skinfold thickness, lean body mass (LBM), content of body fat (%F), mid-arm muscle circumference (MAMC). Laboratory analysis comprised of albumin and total cholesterol. Additionally, each patient underwent a subjective global assessment (SGA). The patients were followed for 36 months. Survival analyses were made with the Kaplan-Meier survival curve and the Cox proportional hazard model. Following SGA, malnutrition was diagnosed in 30 (28%) patients. Importantly, eight of the malnourished patients (27%) were nevertheless overweight or obese. Body weight and BMI showed complete lack of association with the outcome. In Kaplan-Meier analysis low: LBM, MAMC, albumin and cholesterol were significantly related to mortality. Cox analysis revealed that, following adjustment, LBM below median was independently associated with poor outcome (hazard ratio [HR] 3.15, 95% confidence interval [CI] 1.17-8.49, p=0.02). Moreover, the lowest quartile of total cholesterol showed independent association with mortality (HR 8.68, CI 2.14 35.21, p<0.01). Malnutrition is prevalent in patients undergoing PD, and overweight/obesity does not preclude its appearance. The most valuable nutritional indices in predicting outcome in this cohort were LBM and total cholesterol concentration. PMID- 26824293 TI - Cloning, expression, and biochemical characterization of a cold-active GDSL esterase of a Pseudomonas sp. S9 isolated from Spitsbergen island soil. AB - An estS9 gene, encoding an esterase of the psychrotolerant bacterium Pseudomonas sp. S9 was cloned and sequenced. The deduced sequence revealed a protein of 636 amino acid residues with a molecular mass of 69 kDa. Further amino acid sequence analysis revealed that the EstS9 enzyme contained a G-D-S-L motif centered at a catalytic serine, an N-terminal catalytic domain and a C-terminal autotransporter domain. Two recombinant E. coli strains for production of EstS9N (a two domain enzyme) and EstS9Delta (a one domain enzyme) proteins were constructed, respectively. Both recombinant proteins were successfully produced as inclusion bodies and then purified under denaturing conditions. However, because of the low enzymatic activity of the refolded EstS9Delta protein, only the EstS9N protein was further characterized. The purified and refolded EstS9N protein was active towards short-chain p-nitrophenyl esters (C2-C8), with optimal activity for the butyrate (C4) ester. With p-nitrophenyl butyrate as the substrate, the enzyme displayed optimal activity at 35 degrees C and pH 9.0. Additionally, the EstS9N esterase retained ~90% of its activity from 25-40 degrees C and ~40% of its activity at 10 degrees C. Moreover, analysis of its kinetic parameters (Km, kcat, kcat/Km) toward p-nitrophenyl butyrate determined at 15 degrees C and 25 degrees C confirmed that the EstS9 enzyme is cold-adapted. To the best of our knowledge, EstS9 is the third characterized cold-active GDSL-esterase and the first one confirmed to contain an autotransporter domain characteristic for enzymes secreted by the type V secretion system. PMID- 26824294 TI - Conflicting results of non-invasive methods for detection of Helicobacter pylori infection in children with celiac disease - a preliminary study. AB - BACKGROUND: There are no data addressing the usefulness of non-invasive tests for the detection of Helicobacter pylori (HP) infection in celiac disease (CD). AIM: The aim of this study was to compare two most sensitive and specific tests - urea breath test (UBT) and fecal antigen test (FAT) in HP diagnosis in CD patients. MATERIALS AND METHODS: The study comprised of 76 CD patients, 49 healthy subjects (HS) and 35 patients who underwent differential diagnosis due to abdominal pain (AP patients). The presence of HP infection was evaluated using the (13)C isotope labeled UBT and FAT (ELISA). RESULTS: HP infection was diagnosed based on UBT and FAT in 8 (16.3%) and 7 (14.3%) HS, and in 8 (10.5%) CD patients and 12 (34.3%) AP patients, respectively, using both tests. The prevalence of conflicting results in comparison with positive results (obtained with any of the two tests) was distinctly higher (54.5%) in CD group than in other subjects (23.3%); however, due to low HP prevalence, it did not reach the level of significance (p<0.1759). CONCLUSION: CD may increase the risk of divergent results of non-invasive tests used for the detection of HP infection in children. Since UBT is the most reliable test, we suggest its standard use as a method of choice in pediatric CD at least until new evidence emerges supporting a different approach. PMID- 26824295 TI - Vitamin D in the skin physiology and pathology. AB - Vitamin D plays important, pleiotropic role in the maintenance of global homeostasis. Its influence goes far beyond the regulation of calcium and phosphorus balance, as diverse activities of vitamin D and its natural metabolites assure proper functioning of major human organs, including skin. Recently, we reviewed the current understanding of vitamin D impact on human health from historical perspective (Wierzbicka et al. (2014) The renaissance of vitamin D. Acta Biochim Pol 61: 679-686). This article focuses on its functions in the skin. The skin and its appendages, creates a platform connecting and protecting internal organs against, usually harmful, external environment. It uppermost layer - epidermis in order to maintain a protective barrier undergoes a constant exchange of cornified keratinocytes layer. Its disturbance leads to development of serious skin disorders including psoriasis, vitiligo, atopic dermatitis and skin cancer. All of those dermatopathologies have a huge impact on modern societies, affecting not only the physical, but also mental state of patients as well as their social status. Furthermore, multiple human systemic diseases (autoimmune, blood and digestive diseases) have skin manifestation, thus "condition of the skin" often reflects the condition and pathological changes within the internal organs. In humans, the skin is the natural source of vitamin D, which is produced locally from 7-dehydrocholesterol in photoreaction induced by ultraviolet B (UVB) radiation from the sun. It is also well established, that the process of proliferation and differentiation of keratinocytes is tightly regulated by calcium and the active form of vitamin D (1,25(OH)2D3). Thus, the skin physiology is inseparably connected with vitamin D production and activity. Unfortunately, UVB, which is required for vitamin D production, is also known as the main cause of a skin cancer, including melanoma. Here, we are going to review benefits of vitamin D and its analogues in the maintenance of epidermal barrier and its potential use in the treatment of common skin diseases. PMID- 26824296 TI - Sequence-Specific Recognition of MicroRNAs and Other Short Nucleic Acids with Solid-State Nanopores. AB - The detection and quantification of short nucleic acid sequences has many potential applications in studying biological processes, monitoring disease initiation and progression, and evaluating environmental systems, but is challenging by nature. We present here an assay based on the solid-state nanopore platform for the identification of specific sequences in solution. We demonstrate that hybridization of a target nucleic acid with a synthetic probe molecule enables discrimination between duplex and single-stranded molecules with high efficacy. Our approach requires limited preparation of samples and yields an unambiguous translocation event rate enhancement that can be used to determine the presence and abundance of a single sequence within a background of nontarget oligonucleotides. PMID- 26824297 TI - The Association Between Subclinical Hypothyroidism and Metabolic Syndrome as Defined by the ATP III Criteria. AB - The association between subclinical hypothyroidism (SCH) and metabolic syndrome (MetS) is a matter of debate. In this study, we aimed to examine the risk of MetS in SCH through a systematic review and meta-analysis. A systematic search of published literature up to September 2015 was conducted. General population studies were included if they had considered SCH as the independent variable. After data extraction, a meta-analysis was run to assess the odds ratio (OR) of MetS and its components between subclinical hypothyroid and euthyroid groups. Only studies employing Adult Treatment Panel III (ATP III) criteria for MetS were included in the meta-analysis. In the SCH group, female gender was more prevalent [OR = 1.65, 95% confidence interval (95% CI) 1.29-2.13]. Meta-analysis showed no significant difference in MetS prevalence between SCH and euthyroid individuals (OR = 1.13, 95% CI 0.95-1.34). However, the prevalence of central obesity (OR = 1.43, 95% CI 1.04-1.96) was significantly higher in the SCH group. On the other hand, hypertriglyceridemia was more prevalent in the female-only SCH subgroup. In conclusion, although we found some MetS components to be more prevalent in SCH, the prevalence of MetS as defined by ATP III criteria was not increased in SCH. Considerable heterogeneity observed may have influenced the results on MetS components. PMID- 26824298 TI - Reduction of internal carotid artery intima-media thickness in patients with moderate-to-severe obstructive sleep apnea syndrome after nasal surgery and uvulopalatopharyngoplasty. AB - CONCLUSION: Multi-level surgeries for the nasal cavity and palate can reduce the severity of obstructive sleep apnea with major narrowing above the retropalatal airway and reduce the carotid intima-media thickness, which can provide cardiovascular benefits to patients. OBJECTIVE: To evaluate the outcomes of moderate-to-severe obstructive sleep apnea syndrome by surgeries and the change of internal carotid artery intima-media thickness after surgeries. SUBJECTS AND METHODS: Sixty-four patients with obstructive sleep apnea, narrowing at the nasal cavity, and retropalatal airways were enrolled in this study. Fifty-two patients underwent nasal surgery and modified uvulopalatopharyngoplasty. Twelve patients who refused surgeries and continuous positive airway pressure treatment received only conservative treatment. All patients were evaluated within 1 month before and 6 months after treatment using polysomnography, upper airway endoscopy, and B mode ultrasound. RESULTS: The success rate was 61.5% (32/52 patients) in the surgery group. There were significant differences between the surgery group and non-surgery group 6 months after treatment in the apnea hypopnea index, minimum and mean oxygen saturation, blood pressure, triglyceride, total cholesterol, high density lipoprotein cholesterol, low-density lipoprotein cholesterol, and internal Carotid intima-media thickness. The changes in the oxygen saturation and the apnea hypopnea index showed significant correlations with the changes in the intima-media thickness. PMID- 26824299 TI - Analysis of Enantioselective Biotransformations Using a Few Hundred Cells on an Integrated Microfluidic Chip. AB - The investigation of stereoselective biocatalytic transformations at a single cell level is to date an unsolved challenge. Here, we report the development of an integrated microfluidic device which enables the analytical characterization of enantioselective reactions at nanoliter scale by combining whole-cell catalyzed on-chip syntheses, chiral microchip electrophoresis, and label-free detection of enantiomers by deep UV time-resolved fluorescence. Using Escherichia coli expressing recombinant Aspergillus niger epoxide hydrolase as the model enzyme for various enantioselective reactions, we evaluated the approach for downscaling the reaction to a few hundred cells. Our work is thus an important step toward the analysis of single-cell stereoselective biocatalysis. PMID- 26824301 TI - Combined anaerobic digestion and photocatalytic treatment of distillery effluent in fluidized bed reactors focusing on energy conservation. AB - Anaerobic digestion (AD) can remove substantial amount of organic load when applied in treating distillery effluent but it is ineffective in colour reduction. Conversely, photodegradation is effective in colour reduction but has high energy requirement. A study on the synergy of a combined AD and ultra violet (UV) photodegradation treatment of distillery effluent was carried out in fluidized bed reactors to evaluate pollution reduction and energy utilization efficiencies. The combined process improved colour removal from 41% to 85% compared to that of AD employed as a stand-alone process. An overall corresponding total organic carbon (TOC) reduction of 83% was achieved. The bioenergy production by the AD step was 14.2 kJ/g total organic carbon (TOC) biodegraded while UV lamp energy consumption was 0.9 kJ/mg TOC, corresponding to up to 100% colour removal. Electrical energy per order analysis for the photodegradation process showed that the bioenergy produced was 20% of that required by the UV lamp to photodegrade 1 m(3) of undiluted pre-AD treated effluent up to 75% colour reduction. It was concluded that a combined AD-UV system for treatment of distillery effluent is effective in organic load removal and can be operated at a reduced cost. PMID- 26824300 TI - Methemoglobin Formation and Characterization of Hemoglobin Adducts of Carcinogenic Aromatic Amines and Heterocyclic Aromatic Amines. AB - Arylamines (AAs) and heterocyclic aromatic amines (HAAs) are structurally related carcinogens formed during the combustion of tobacco or cooking of meat. They undergo cytochrome P450 mediated N-hydroxylation to form metabolites which bind to DNA and lead to mutations. The N-hydroxylated metabolites of many AAs also can undergo a co-oxidation reaction with oxy-hemolgobin (HbO2) to form methemoglobin (met-Hb) and the arylnitroso intermediates, which react with the beta-Cys(93) chain of Hb to form Hb-arylsulfinamide adducts. The biochemistry of arylamine metabolism has been exploited to biomonitor certain AAs through their Hb arylsulfinamide adducts in humans. We examined the reactivity of HbO2 with the N hydroxylated metabolites of 4-aminobiphenyl (ABP, HONH-ABP), aniline (ANL, HONH ANL), and the HAAs 2-amino-9H-pyrido[2,3-b]indole (AalphaC, HONH-AalphaC), 2 amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, HONH-PhIP), and 2-amino-3,8 dimethylimidazo[4,5-f]quinoxaline (MeIQx, HONH-MeIQx). HONH-ABP, HO-ANL, and HONH AalphaC induced methemoglobinemia and formed Hb sulfinamide adducts. However, HONH-MeIQx and HONH-PhIP did not react with the oxy-heme complex, and met-Hb formation and chemical modification of the beta-Cys(93) residue were negligible. Molecular modeling studies showed that the distances between the H-ON-AA or H-ON HAA substrates and the oxy-heme complex of HbO2 were too far away to induce methemoglobinemia. Different conformational changes in flexible helical and loop regions around the heme pocket induced by the H-ON-AA or H-ON-HAAs may explain the different proclivities of these chemicals to induce methemoglobinemia. Hb Cys(93beta) sulfinamide and sulfonamide adducts of ABP, ANL, and AalphaC were identified, by Orbitrap MS, following the proteolysis of Hb with trypsin, Glu-C, or Lys-C. Hb sulfinamide and sulfonamide adducts of ABP were identified in the blood of mice exposed to ABP, by Orbitrap MS. This is the first report of the identification of intact Hb sulfinamide adducts of carcinogenic AAs in vivo. The high reactivity of HONH-AalphaC with HbO2 suggests that the Hb sulfinamide adduct of AalphaC may be a promising biomarker of exposure to this HAA in humans. PMID- 26824303 TI - Synthesis and Antitumor Properties of BQC-Glucuronide, a Camptothecin Prodrug for Selective Tumor Activation. AB - Major limitations of camptothecin anticancer drugs (toxicity, nonselectivity, water insolubility, inactivation by human serum albumin) may be improved by creating glucuronide prodrugs that rely on beta-glucuronidase for their activation. We found that the camptothecin derivative 5,6-dihydro-4H benzo[de]quinoline-camptothecin (BQC) displays greater cytotoxicity against cancer cells than the clinically used camptothecin derivatives SN-38 and topotecan even in the presence of human serum albumin. We synthesized the prodrug BQC-glucuronide (BQC-G), which was 4000 times more water soluble and 20-40 times less cytotoxic than BQC. Importantly, even in the presence of human serum albumin, BQC-G was efficiently hydrolyzed by beta-glucuronidase and produced greater cytotoxicity (IC50 = 13 nM) than camptothecin, 9-aminocamptothecin, SN 38, or topotecan (IC50 > 3000, 1370, 48, and 28 nM, respectively). BQC-G treatment of mice bearing human colon cancer xenografts with naturally or artificially elevated beta-glucuronidase activity produced significant antitumor activity, showing that BQC-G is a potent prodrug suitable for selective intratumoral drug activation. PMID- 26824302 TI - Excitable waves and direction-sensing in Dictyostelium discoideum: steps towards a chemotaxis model. AB - In recent years, there have been significant advances in our understanding of the mechanisms underlying chemically directed motility by eukaryotic cells such as Dictyostelium. In particular, the local excitation and global inhibition (LEGI) model has proven capable of providing a framework for quantitatively explaining many experiments that present Dictyostelium cells with tailored chemical stimuli and monitor their subsequent polarization. In their natural setting, cells generate their own directional signals via the detection and secretion of cyclic adenosine monophosphate (cAMP). Here, we couple the LEGI approach to an excitable medium model of the cAMP wave-field that is propagated by the cells and investigate the possibility for this class of models to enable accurate chemotaxis to the cAMP waveforms expected in vivo. Our results indicate that the ultra-sensitive version of the model does an excellent job in providing natural wave rectification, thereby providing a compelling solution to the 'back-of-the wave paradox' during cellular aggregation. PMID- 26824304 TI - Excluding Contact Electrification in Surface Potential Measurement Using Kelvin Probe Force Microscopy. AB - Kelvin probe force microscopy (KPFM), a characterization method that could image surface potentials of materials at the nanoscale, has extensive applications in characterizing the electric and electronic properties of metal, semiconductor, and insulator materials. However, it requires deep understanding of the physics of the measuring process and being able to rule out factors that may cause artifacts to obtain accurate results. In the most commonly used dual-pass KPFM, the probe works in tapping mode to obtain surface topography information in a first pass before lifting to a certain height to measure the surface potential. In this paper, we have demonstrated that the tapping-mode topography scan pass during the typical dual-pass KPFM measurement may trigger contact electrification between the probe and the sample, which leads to a charged sample surface and thus can introduce a significant error to the surface potential measurement. Contact electrification will happen when the probe enters into the repulsive force regime of a tip-sample interaction, and this can be detected by the phase shift of the probe vibration. In addition, the influences of scanning parameters, sample properties, and the probe's attributes have also been examined, in which lower free cantilever vibration amplitude, larger adhesion between the probe tip and the sample, and lower cantilever spring constant of the probe are less likely to trigger contact electrification. Finally, we have put forward a guideline to rationally decouple contact electrification from the surface potential measurement. They are decreasing the free amplitude, increasing the set-point amplitude, and using probes with a lower spring constant. PMID- 26824306 TI - CATTELL AND EYSENCK FACTOR SCORES RELATED TO COMREY PERSONALITY FACTORS. AB - The Eysenck Personality Inventory, the Cattell 16 PF Inventory, and the Comrey Personality Inventory were administered to 272 volunteers. Eysenck and Cattell factor scores were correlated with scores over homogeneous item groups (FHIDs) which define the Comrey test factors. This matrix was factor analyzed to relate the Eysenck and Cattell factor scores to the factor structure underlying the Comrey test. The Eysenck Neuroticism, Comrey Neuroticism, and Cattell second order Anxiety factors appeared to match. The Eysenck Introversion and the Comrey Shyness factors also matched. The 16 Cattell primary factors overlapped but did not match with the Comrey factors. PMID- 26824305 TI - Among Patients Undergoing Ablative Treatment for Oral Cancer, Does the Provision of Oral Rehabilitation Improve the Quality of Life? A Review of the Current Literature. AB - PURPOSE: The impact of oral cancer and its treatment is well documented; therefore, oral rehabilitation (OH; eg, with prosthetics, osseointegrated implants, etc) can be indicated to restore some level of form, function, and well being. The purpose of this study was to review the current literature and evaluate the impact of OH on quality of life (QoL) after ablative surgery. MATERIALS AND METHODS: A systematic literature search was conducted using EMBASE, MEDLINE, and PsychINFO. The study population was composed of all articles published from 2000 to 2015. To be included, studies had to use validated, specific head and neck QoL measurements (European Organization for Research and Treatment of Cancer QoL Head and Neck Module or University of Washington QoL Questionnaire). Only 8 articles met these inclusion criteria. In this review, OH was the primary predictor variable and QoL was the primary outcome variable. RESULTS: The 8 articles reviewed used a range of designs, including 1 randomized controlled trial, 3 prospective cohort studies, 3 case series, and 1 single measurement cross-sectional descriptive study. Sample sizes were small (n = 26 to 102), and there was limited randomization and control of intervention and comparator groups. The overall level of evidence was weak. All studies showed a link between OH and QoL, but the results varied in significance (P < .01 to P = .95). CONCLUSION: Overall, there appears to be improvement in QoL to varying degrees after OH. However, a more systematic use of QoL measurements is needed before any definitive conclusions can be drawn. PMID- 26824307 TI - ITEMS AND PERSONS: FORMAL DUALS AND PSYCHOLOGICAL DIFFERENCES. AB - A matrix of the responses of persons (rows) to items (columns) can be analyzed for persons as the dual of the usual analyses for items. In personality tests, the stability of items varies with mean distance between the item and the points for persons, and the dual holds for persons. For items, the item- test correlation varies somewhat with stability and with the frequency of appropriate response processes (i.e., Ss answering the item as E intended them to), but stability and appropriateness are not correlated. For persons, the per- son-group correlation is independent of stability and appropriateness, these latter variables being correlated. Thus the pattern of relationships among item indices is different from that for the dual indices for people. Persons being complex, they approach personality test items in diverse ways about which little is known today. PMID- 26824308 TI - THE WORK COMPONENTS STUDY (WCS): A REVISED SET OF MEASURES FOR WORK MOTIVATION. AB - The present study, through reanalysis of earlier data and the analysis of data from a new sample, reports on the refinement of the Work Components Study (WCS). An earlier study yielded six scores but the present one suggests that one of them should be broken into two, yielding seven scores. It is shown that the internal consistency of these scores is satisfactory and that the scores are relatively independent of each other. Finally, the utility of the scores is evaluated by showing their relationships with measures of personality, ability, and aspirations. PMID- 26824309 TI - THE GENERALITY OF BEHAVIORAL DATA II: REPLICATION OF AN EXPERIMENT ON GENERALIZATION FROM OBSERVATIONS ON ONE OCCASION'. AB - In two experiments previously reported the effect was studied of variation of task and group composition on ratings of behavior based on observation of individuals in group situations. The experiment reported here was planned as a replication of one of these studies. The main results of the two previous experiments were completely confirmed: When the situation variation encompassed both task and group com- position simultaneously the relationship was random between ratings made independently by two teams of judges, after one observation instance for each team. PMID- 26824310 TI - AN ECOLOGICAL ANALYSIS OF PSYCHIATRIC HOSPITALIZATIONS. AB - In order to develop some understanding of community social structure and its association with psychiatric inpatient medical care patterns, first admission rates for psychiatric disorders into both public and private facilities were determined for each of the 33 census tracts of Pueblo, Colorado. At the same time a cluster analysis was made of the structure of these tracts. Four well- defined clusters were identified (socio-economic affluence, young marrieds, social isolation, and social disequilibrium) and strikingly high differential relationships found between the cluster scores and psychiatric inpatient care patterns. Implications of the findings for preventive strategies and for. social etiology hypotheses are presented. PMID- 26824311 TI - MULTIPLE CLUSTERS, TYPES, AND DIMENSIONS FROM ITERATIVE INTERCOLUMNAR CORRELATIONAL ANALYSIS. AB - This paper extends Intercolumnar Correlational Analysis from a single, hierarchical, classification method to a multiple, hierarchical, classification method. Some advantages of the method over most other methods are: (a) it builds hierarchical classifications from the top down and thus uses all indices of every matrix or submatrix in all decisions, and (b) it provides a comprehensive base for defining the major patterns of the first hierarchical system. PMID- 26824312 TI - CLUSTER ORIENTED FACTOR SOLUTIONS: OBLIQUE POWERED VECTOR FACTOR ANALYSIS. AB - Good simple structure is the natural consequence of fitting hyperplanes to cluster centroids in analyses of data in which distinct cluster configuration exists. The oblique powered vector factor analysis utilizes a preliminary direct orthogonal solution to identify clusters, passes primary axes through the cluster centroids and produces final oblique reference structure by simple trans- formation. The hyperplane for each oblique factor is fitted precisely to the centroids for clusters of variables projecting primarily on other factors. The method is computationally efficient and has in practical applications produced meaningful results with good simple structure characteristics. An illustration of application to the 24-variable Harman problem is included. PMID- 26824313 TI - A NEW MATRIX FOR THE ASSESSMENT OF FACTOR CONTRIBUTIONS. AB - The matrix product of the initial factor loading matrix times the least- squares orthonormal approximation to the general oblique transformation matrix is suggested to be the most adequate matrix for the evaluation of the contributions of factors to variables. This factor contribution matrix can also re- place the primary factor pattern matrix in evaluating oblique simple structure. PMID- 26824314 TI - THE RATIONALE OF THE GUTTMAN-LINGOES NONMETRIC SERIES: A LETTER TO DOCTOR PHILIP RUNKEL. PMID- 26824315 TI - -BRIEF REPORT: ON THE DANGER INVOLVED IN THE USE OF TESTS WHICH MEASURE FACTORS. AB - relatively pure factors. Measures of factors developed through the use of relationships among individual differences are not necessarily measures of factors is the same sense when they are used as dependent variables in experiments designed to determine the effect of an independent variable. Until a measure of a factor (developed from correlations among individual differences) has been empirically demonstrated to be a factor in an experimental sense (correlated mean changes), the construct validity of measures of factors must remain zero when the measures are used as dependent variables in experiments. Factor analytic procedures have produced tests which purport to measure. PMID- 26824316 TI - BRIEF REPORT: RELATIONSHIPS OF CIGARETTE SMOKING TO ACADEMIC ACHIEVEMENT, COGNITIVE ABILITIES, AND ATTITUDES TOWARD AUTHORITY. AB - Published research has linked cigarette smoking with (1) inferior academic performance, (2) lower quantitative scholastic aptitude, and (3) negative attitude toward authority figures. Using data from 2315 freshmen (1368 males and 967 females), these three relationships were confirmed. Further- more, analyses of covariance clearly demonstrated that neither scholastic aptitude nor attitudes toward authority-although themselves related to academic performance would account for the relationship between cigarette smoking and grade-point average. PMID- 26824317 TI - Evaluating the morphology of erythrocyte population: An approach based on atomic force microscopy and flow cytometry. AB - Erythrocyte morphology is gaining importance as a powerful pathological index in identifying the severity of any blood related disease. However, the existing technique of quantitative microscopy is highly time consuming and prone to personalized bias. On the other hand, relatively unexplored, complementary technique based on flow cytometry has not been standardized till date, particularly due to the lack of a proper morphological scoring scale. In this article, we have presented a new approach to formulate a non-empirical scoring scale based on membrane roughness (R(rms)) data obtained from atomic force microscopy. Subsequently, the respective morphological quantifier of the whole erythrocyte population, commonly known as morphological index, was expressed as a function of highest correlated statistical parameters of scattered signal profiles generated by flow cytometry. Feed forward artificial neural network model with multilayer perceptron architecture was used to develop the intended functional form. High correlation coefficient (R(2) = 0.95), even for model formulation exclusive samples, clearly indicates the universal validity of the proposed model. Moreover, a direct pathological application of the proposed model has been illustrated in relation to patients, diagnosed to be suffering from a wide variety of cancer. PMID- 26824318 TI - MIIP accelerates epidermal growth factor receptor protein turnover and attenuates proliferation in non-small cell lung cancer. AB - The migration and invasion inhibitory protein (MIIP) has been discovered recently to have inhibitory functions in cell proliferation and migration. Overexpression of MIIP reduced the intracellular steady-state level of epidermal growth factor receptor (EGFR) protein in lung cancer cells with no effect on EGFR mRNA expression compared to that in the control cells. This MIIP-promoted EGFR protein degradation was reversed by proteasome and lysosome inhibitors, suggesting the involvement of both proteasomal and lysosomal pathways in this degradation. This finding was further validated by pulse-chase experiments using 35S-methionine metabolic labeling. We found that MIIP accelerates EGFR protein turnover via proteasomal degradation in the endoplasmic reticulum and then via the lysosomal pathway after its entry into endocytic trafficking. MIIP-stimulated downregulation of EGFR inhibits downstream activation of Ras and blocks the MEK signal transduction pathway, resulting in inhibition of cell proliferation. The negative correlation between MIIP and EGFR protein expression was validated in lung adenocarcinoma samples. Furthermore, the higher MIIP protein expression predicts a better overall survival of Stage IA-IIIA lung adenocarcinoma patients who underwent radical surgery. These findings reveal a new mechanism by which MIIP inhibits cell proliferation. PMID- 26824319 TI - Parthenolide induces MITF-M downregulation and senescence in patient-derived MITF M(high) melanoma cell populations. AB - The activity of the M isoform of microphthalmia-associated transcription factor (MITF-M) has been attributed to regulation of differentiation, proliferation, survival and senescence of melanoma cells. MITF expression was shown to be antagonized by the activation of transcription factor NF-kappaB. Parthenolide, an inhibitor of NF-kappaB, has not been yet reported to affect MITF-M expression. Our results obtained in patient-derived melanoma cell populations indicate that parthenolide efficiently decreases the MITF-M level. This is neither dependent on p65/NF-kappaB signaling nor RAF/MEK/ERK pathway activity as inhibition of MEK by GSK1120212 (trametinib) and induction of ERK1/2 activity by parthenolide itself do not interfere with parthenolide-triggered depletion of MITF-M in both wild type BRAF and BRAF(V600E) melanoma populations. Parthenolide activity is not prevented by inhibitors of caspases, proteasomal and lysosomal pathways. As parthenolide reduces MITF-M transcript level and HDAC1 protein level, parthenolide-activated depletion of MITF-M protein may be considered as a result of transcriptional regulation, however, the influence of parthenolide on other elements of a dynamic control over MITF-M cannot be ruled out. Parthenolide induces diverse effects in melanoma cells, from death to senescence. The mode of the response to parthenolide is bound to the molecular characteristics of melanoma cells, particularly to the basal MITF-M expression level but other cell autonomous differences such as NF-kappaB activity and MCL-1 level might also contribute. Our data suggest that parthenolide can be developed as a drug used in combination therapy against melanoma when simultaneous inhibition of MITF-M, NF kappaB and HDAC1 is needed. PMID- 26824321 TI - Differential regulation of mTOR signaling determines sensitivity to AKT inhibition in diffuse large B cell lymphoma. AB - Agents that target components of the PI3K/AKT/mTOR pathway are under investigation for the treatment of diffuse large B cell lymphoma (DLBCL). Given the highly heterogeneous nature of DLBCL, it is not clear whether all subtypes of DLBCL will be susceptible to PI3K pathway inhibition, or which kinase within this pathway is the most favorable target. Pharmacological profiling of a panel of DLBCL cell lines revealed a subset of DLBCL that was resistant to AKT inhibition. Strikingly, sensitivity to AKT inhibitors correlated with the ability of these inhibitors to block phosphorylation of S6K1 and ribosomal protein S6. Cell lines resistant to AKT inhibition activated S6K1 independent of AKT either through upregulation of PIM2 or through activation by B cell receptor (BCR) signaling components. Finally, combined inhibition of AKT and BTK, PIM2, or S6K1 proved to be an effective strategy to overcome resistance to AKT inhibition in DLBCL. PMID- 26824320 TI - Lapatinib inhibits CIP2A/PP2A/p-Akt signaling and induces apoptosis in triple negative breast cancer cells. AB - We tested the efficacy of lapatinib, a dual tyrosine kinase inhibitor which interrupts the HER2 and epidermal growth factor receptor (EGFR) pathways, in a panel of triple-negative breast cancer (TNBC) cells, and examined the drug mechanism. Lapatinib showed an anti-proliferative effect in HCC 1937, MDA-MB-468, and MDA-MB-231 cell lines. Lapatinib induced significant apoptosis and inhibited CIP2A and p-Akt in a dose and time-dependent manner in the three TNBC cell lines. Overexpression of CIP2A reduced lapatinib-induced apoptosis in MDA-MB-468 cells. In addition, lapatinib increased PP2A activity (in relation to CIP2A inhibition). Moreover, lapatinib-induced apoptosis and p-Akt downregulation was attenuated by PP2A antagonist okadaic acid. Furthermore, lapatinib indirectly decreased CIP2A transcription by disturbing the binding of Elk1 to the CIP2A promoter. Importantly, lapatinib showed anti-tumor activity in mice bearing MDA-MB-468 xenograft tumors, and suppressed CIP2A as well as p-Akt in these xenografted tumors. In summary, inhibition of CIP2A determines the effects of lapatinib induced apoptosis in TNBC cells. In addition to being a dual tyrosine kinase inhibitor of HER2 and EGFR, lapatinib also inhibits CIP2A/PP2A/p-Akt signaling in TNBC cells. PMID- 26824322 TI - Cold inducible RNA binding protein upregulation in pituitary corticotroph adenoma induces corticotroph cell proliferation via Erk signaling pathway. AB - Cushing's disease is caused by pituitary corticotroph adenoma, and the pathogenesis of it has remained obscure. Here, we showed that cold inducible RNA binding protein (CIRP) was markedly elevated in corticotroph tumors. Forced overexpression of CIRP in murine AtT20 pituitary corticotroph cell line increased corticotroph precursor hormone proopiomelanocortin (POMC) transcription, ACTH secretion and cellular proliferation. In vivo, CIRP overexpression promotes murine corticotroph tumor growth and enhances ACTH production. Mechanistically, we show that CIRP could promote AtT20 cells proliferation by inducing cyclinD1 and decreasing p27 expression via Erk1/2 signaling pathway. Clinically, CIRP overexpression is significantly correlated with Cushing's disease recurrence. CIRP appears to play a critical tumorigenesis function in Cushing's disease and its expression might be a useful biomarker for tumor recurrence. PMID- 26824323 TI - Inhibition of O-GlcNAc transferase activity reprograms prostate cancer cell metabolism. AB - Metabolic networks are highly connected and complex, but a single enzyme, O GlcNAc transferase (OGT) can sense the availability of metabolites and also modify target proteins. We show that inhibition of OGT activity inhibits the proliferation of prostate cancer cells, leads to sustained loss of c-MYC and suppresses the expression of CDK1, elevated expression of which predicts prostate cancer recurrence (p=0.00179). Metabolic profiling revealed decreased glucose consumption and lactate production after OGT inhibition. This decreased glycolytic activity specifically sensitized prostate cancer cells, but not cells representing normal prostate epithelium, to inhibitors of oxidative phosphorylation (rotenone and metformin). Intra-cellular alanine was depleted upon OGT inhibitor treatment. OGT inhibitor increased the expression and activity of alanine aminotransferase (GPT2), an enzyme that can be targeted with a clinically approved drug, cycloserine. Simultaneous inhibition of OGT and GPT2 inhibited cell viability and growth rate, and additionally activated a cell death response. These combinatorial effects were predominantly seen in prostate cancer cells, but not in a cell-line derived from normal prostate epithelium. Combinatorial treatments were confirmed with two inhibitors against both OGT and GPT2. Taken together, here we report the reprogramming of energy metabolism upon inhibition of OGT activity, and identify synergistically lethal combinations that are prostate cancer cell specific. PMID- 26824326 TI - Gestational diabetes mellitus diagnosis and treatment goals: measurement and measures. AB - Gestational diabetes mellitus (GDM) is defined as diabetes diagnosed during pregnancy that is not clearly overt diabetes. It is the most common complication of pregnancy and is the most common type of diabetes during pregnancy. Its high prevalence is determined by the increasing epidemic of obesity and by the diagnostic criteria applied. New criteria are currently accepted by a number of professional societies, but considerable controversies still exist concerning diagnosis of GDM. GDM can cause significant short term and long term problems for mother and offspring, including but not limited to cesarean delivery, birth trauma, as well as the development of type 2 diabetes in mother and offspring in the future. Although the consequences of poorly controlled GDM are evident, there continues to be controversy regarding the most appropriate diagnostic criteria, the metabolic aims in controlling GDM, the ability to diagnose GDM in early pregnancy, and the efficiency of treatment in order to improve pregnancy outcomes. This review focuses on current recommendations of professional medical societies and evidence base for GDM diagnosis and glycemic goals of treatment. Available evidence for the optimal time and frequency of self-monitoring of blood glucose and the role of glycated haemoglobin in GDM is also provided in this review. PMID- 26824324 TI - Metformin inhibits 17beta-estradiol-induced epithelial-to-mesenchymal transition via betaKlotho-related ERK1/2 signaling and AMPKalpha signaling in endometrial adenocarcinoma cells. AB - The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17beta estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17beta-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17beta-estradiol-induced cell proliferation and reversed 17beta-estradiol-induced EMT in Ishikawa cells. In addition, metformin increased the expression of betaKlotho, a fibroblast growth factors (FGFs) coreceptor, and decreased ERK1/2 phosphorylation in both Ishikawa and KLE cells. Decreased expression of betaKlotho was noted in human endometrial adenocarcinomas, and plasmid-driven expression of betaKlotho in Ishikawa cells abolished 17beta estradiol-induced EMT via inhibiting ERK1/2 signaling. betaKlotho expression and metformin show synergetic effects on the proliferation and the EMT in Ishikawa cells. Furthermore, we demonstrated that the anti-EMT effects of metformin could be partly abolished by introducing Compound C, a specific AMPKalpha signaling inhibitor. In conclusion, metformin abolishes 17beta-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating betaKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKalpha signaling. Our study provides novel mechanistic insight into the anti-tumor effects of metformin. PMID- 26824327 TI - Foreign Body Giant Cell-Related Encapsulation of a Synthetic Material Three Years After Augmentation. AB - Bone substitute materials of different origin and chemical compositions are frequently used in augmentation procedures to enlarge the local bone amount. However, relatively little data exist on the long-term tissue reactions. The presented case reports for the first time histological and histomorphometrical analyses of a nanocrystaline hydroxyapatite-based bone substitute material implanted in the human sinus cavity after an integration period of 3 years. The extracted biopsy was analyzed histologically and histomorphometrically with focus on the tissue reactions, vascularization, new bone formation, and the induction of a foreign body reaction. A comparably high rate of connective tissue (48.25%) surrounding the remaining bone substitute granules (42.13%) was observed. Accordingly, the amount of bone tissue (9.62%) built the smallest fraction within the biopsy. Further, tartrate-resistant acid phosphatase-positive and -negative multinucleated giant cells (4.35 and 3.93 cells/mm(2), respectively) were detected on the material-tissue interfaces. The implantation bed showed a mild vascularization of 10.03 vessels/mm(2) and 0.78%. The present case report shows that after 3 years, a comparable small amount of bone tissue was observable. Thus, the foreign body response to the bone substitute seems to be folded without further degradation or regeneration. PMID- 26824325 TI - Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving cannabinoid receptor CB2. AB - Chronic pain is commonly and closely correlated with inflammation. Both cannabinoid signaling and mesenchymal stem cells (MSCs) have been demonstrated to reduce inflammatory pain. Although cannabinoid signaling is essential for mesenchymal stem cell survival and differentiation, little is known about its role in modulatory effect of MSCs on inflammation and pain sensitivity. Here we showed that mouse bone-marrow derived MSCs (BM-MSCs) expressed both cannabinoid receptor type 1 and 2 (CB1 and CB2). CB2 expression level in BM-MSCs increased with their maturation. In addition, we found that tetrahydrocannabinol (THC) activated CB2 receptor and ERK signaling, consequently enhancing the modulation of MSCs on inflammation-associated cytokine release from lipopolysaccharides stimulated microglia. Consistent with in vitro data, THC pretreatment enhanced the immunomodulatory effects of BM-MSC on thermal hyperalgesia and mechanical allodynia in chronic constriction injury model, by decreasing the release of pro inflammation cytokines. Our study revealed the crucial role of THC in promoting the immunomodulatory effects of MSCs and proposed a new strategy to alleviate pain based on stem cells therapy. PMID- 26824328 TI - Eutrophication-Driven Hypoxia in the East China Sea off the Changjiang Estuary. AB - Coastal hypoxia is an increasingly recognized environmental issue of global concern to both the scientific community and the general public. We assessed the relative contributions from marine and terrestrially sourced organic matter that were responsible for oxygen consumption in a well-studied seasonal coastal hypoxic zone, the East China Sea off the Changjiang Estuary. Our fieldwork was conducted in August 2011 during reinstatement of a subsurface hypoxia, when we observed a continuous decline of dissolved oxygen along with production of dissolved inorganic carbon resulting from organic carbon remineralization. On the basis of a three end-member mixing model and determinations of the stable isotopic compositions of dissolved inorganic carbon (delta(13)CDIC), the end product of particulate organic carbon (POC) degradation, we quantified the delta(13)C value of the remineralized organic carbon (delta(13)COCx), which was 18.5 +/- 1.00/00. This isotopic composition was very similar to the delta(13)C of marine sourced POC produced in situ (-18.5 +/- 0.30/00) rather than that of the terrestrially sourced POC (-24.4 +/- 0.20/00). We concluded that marine-sourced organic matter, formed by eutrophication-induced marine primary production, was the dominant oxygen consumer in the subsurface hypoxic zone in the East China Sea off the Changjiang Estuary. PMID- 26824329 TI - How Leucocyte Cell Membrane Modified Janus Microcapsules are Phagocytosed by Cancer Cells. AB - Modern drug delivery systems rely on either antibody-based single-surface recognition or on surface-hydrophobicity-based approaches. For a tumor showing various surface mutations, both approaches fail. This publication hereby presents Janus capsules based on polyelectrolyte multilayer microcapsules exhibiting human leucocyte (THP-1 cell line) cell membranes for discriminating HUVEC cells from three different cancer cell lines. Despite destroying the cellular integrity of leucocyte cells, the modified Janus capsules are able to adhere to cancer cells. Leucocyte cell-membrane-coated Janus capsules are phagocytosed with the cellular membrane part pointing to the cells. PMID- 26824330 TI - Proteome Scale-Protein Turnover Analysis Using High Resolution Mass Spectrometric Data from Stable-Isotope Labeled Plants. AB - Protein turnover is an important aspect of the regulation of cellular processes for organisms when responding to developmental or environmental cues. The measurement of protein turnover in plants, in contrast to that of rapidly growing unicellular organismal cultures, is made more complicated by the high degree of amino acid recycling, resulting in significant transient isotope incorporation distributions that must be dealt with computationally for high throughput analysis to be practical. An algorithm in R, ProteinTurnover, was developed to calculate protein turnover with transient stable isotope incorporation distributions in a high throughput automated manner using high resolution MS and MS/MS proteomic analysis of stable isotopically labeled plant material. ProteinTurnover extracts isotopic distribution information from raw MS data for peptides identified by MS/MS from data sets of either isotopic label dilution or incorporation experiments. Variable isotopic incorporation distributions were modeled using binomial and beta-binomial distributions to deconvolute the natural abundance, newly synthesized/partial-labeled, and fully labeled peptide distributions. Maximum likelihood estimation was performed to calculate the distribution abundance proportion of old and newly synthesized peptides. The half life or turnover rate of each peptide was calculated from changes in the distribution abundance proportions using nonlinear regression. We applied ProteinTurnover to obtain half-lives of proteins from enriched soluble and membrane fractions from Arabidopsis roots. PMID- 26824331 TI - Modelling Feedback Excitation, Pacemaker Properties and Sensory Switching of Electrically Coupled Brainstem Neurons Controlling Rhythmic Activity. AB - What cellular and network properties allow reliable neuronal rhythm generation or firing that can be started and stopped by brief synaptic inputs? We investigate rhythmic activity in an electrically-coupled population of brainstem neurons driving swimming locomotion in young frog tadpoles, and how activity is switched on and off by brief sensory stimulation. We build a computational model of 30 electrically-coupled conditional pacemaker neurons on one side of the tadpole hindbrain and spinal cord. Based on experimental estimates for neuron properties, population sizes, synapse strengths and connections, we show that: long-lasting, mutual, glutamatergic excitation between the neurons allows the network to sustain rhythmic pacemaker firing at swimming frequencies following brief synaptic excitation; activity persists but rhythm breaks down without electrical coupling; NMDA voltage-dependency doubles the range of synaptic feedback strengths generating sustained rhythm. The network can be switched on and off at short latency by brief synaptic excitation and inhibition. We demonstrate that a population of generic Hodgkin-Huxley type neurons coupled by glutamatergic excitatory feedback can generate sustained asynchronous firing switched on and off synaptically. We conclude that networks of neurons with NMDAR mediated feedback excitation can generate self-sustained activity following brief synaptic excitation. The frequency of activity is limited by the kinetics of the neuron membrane channels and can be stopped by brief inhibitory input. Network activity can be rhythmic at lower frequencies if the neurons are electrically coupled. Our key finding is that excitatory synaptic feedback within a population of neurons can produce switchable, stable, sustained firing without synaptic inhibition. PMID- 26824333 TI - Quantitative phase measurements of tendon collagen fibres. AB - Collagen is the main component of structural mammalian tissues. In tendons, collagen is arranged into fibrils with diameters ranging from 30 nm to 500 nm. These fibrils are further assembled into fibres several micrometers in diameter. Upon excessive thermal or mechanical stress, damage may occur in tendons at all levels of the structural hierarchy. At the fibril level, reported damage includes swelling and the appearance of discrete sites of plastic deformation that are best observed at the nanometer-scale using, for example, scanning electron microscopy. In this paper, digital in-line holographic microscopy is used for quantitative phase imaging to measure both the refractive index and diameter of collagen fibres in a water suspension in the native state, after thermal treatments, and after mechanical overload. Fibres extracted from tendons and subsequently exposed to 70 degrees C for 5, 15, or 30 minutes show a significant decrease in refractive index and an increase in diameter. A significant increase in refractive index is also observed for fibres extracted from tendons that were subjected to five tensile overload cycles. PMID- 26824334 TI - Hydrophobin-Encapsulated Quantum Dots. AB - The phase transfer of quantum dots to water is an important aspect of preparing nanomaterials that are suitable for biological applications, and although numerous reports describe ligand exchange, very few describe efficient ligand encapsulation techniques. In this report, we not only report a new method of phase transferring quantum dots (QDs) using an amphiphilic protein (hydrophobin) but also describe the advantages of using a biological molecule with available functional groups and their use in imaging cancer cells in vivo and other imaging applications. PMID- 26824336 TI - Smoking reduction and quality of life in chronic patients with schizophrenia in a Chinese population--A pilot study. AB - BACKGROUND AND OBJECTIVES: Tobacco use is a significant public health issue on a global scale. Prevalence of daily tobacco smoking for men in China is much higher than in the United States. Although prevailing literature suggests a negative relationship between smoking and quality of life, this pilot study sought to evaluate whether smoking reduction/cessation impacted on the perception of quality of life in an in-patient population in China. METHODS: Twenty Chinese patients meeting DSM-IV criteria for schizophrenia were recruited from Beijing Hui-Long-Guan Hospital, an in-patient facility in Beijing, China, for participation in this 4-week study. Seventeen participants with schizophrenia completed the study and were included in the final analysis. Cigarette consumption was recorded daily and the World Health Organization Quality of Life BREF (WHOQOL-BREF) was completed at baseline and at week 4. The relationships between smoking and perceived quality of life were evaluated using correlations between changes in WHOQOL-BREF and changes in cigarettes consumed as measured from baseline to week 4. RESULTS: We found an increase in perceived quality of life in the social relationships domain with increased cigarette consumption in contrast to a decrease in this domain with decreased consumption. However, decreased cigarette consumption was associated with an increase in the psychological domain compared to the social domain. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: These associations suggest a need for interventions to improve the social relationship perceptions with any successful reduction in cigarette consumption among Chinese schizophrenics in order to match their perceived psychological improvement. PMID- 26824335 TI - Is insulin-like growth factor-I a good marker for treatment adherence in growth hormone deficiency in adulthood? AB - OBJECTIVE: There is a paucity of studies on adherence to growth hormone treatment in growth hormone deficient (GHD) adults. Therefore, this study reports on adherence to GH-replacement therapy in adults with GHD, with a special focus on the course and potential predictors of nonadherence. DESIGN: Retrospective single centre cohort study. PATIENTS: From the local patient database, 179 suitable patients with GHD were identified. MEASUREMENTS: The primary outcome was adherence assessed by calculating the percentage of available prescription data in comparison with recommended GH dosages over a mean follow-up period of 92.4 months. Patients were categorized into five adherence categories ranging from <20% to >80%. RESULTS: Mean overall adherence was 74.0%, with 52.9% of patients falling into the adherence group of >80% and 8.8% of <20%. There was a significant drop in adherence (9.8%) between the first and second years of treatment (P < 0.001). Patients with childhood-onset GHD were significantly less adherent to GH treatment than patients with adult-onset GHD (62.0% vs 77.0%, P = 0.012); however, this finding was no longer significant after including age as a covariate. Frequency of IGF-1 levels lying outside the age- and sex-specific reference range was not a good indicator for adherence. CONCLUSION: Although overall adherence was relatively high in our study sample, there is a significant amount of patients who should be regarded as nonadherent. This applies in particular to younger patients. Treating physicians should be aware of the fact that IGF-1 levels do not seem to be a good indicator for adherence. PMID- 26824332 TI - The History, Status, Gaps, and Future Directions of Neurotoxicology in China. AB - BACKGROUND: Rapid economic development in China has produced serious ecological, environmental, and health problems. Neurotoxicity has been recognized as a major public health problem. The Chinese government, research institutes, and scientists conducted extensive studies concerning the source, characteristics, and mechanisms of neurotoxicants. OBJECTIVES: This paper presents, for the first time, a comprehensive history and review of major sources of neurotoxicants, national bodies/legislation engaged, and major neurotoxicology research in China. METHODS: Peer-reviewed research and pollution studies by Chinese scientists from 1991 to 2015 were examined. PubMed, Web of Science and Chinese National Knowledge Infrastructure (CNKI) were the major search tools. RESULTS: The central problem is an increased exposure to neurotoxicants from air and water, food contamination, e-waste recycling, and manufacturing of household products. China formulated an institutional framework and standards system for management of major neurotoxicants. Basic and applied research was initiated, and international cooperation was achieved. The annual number of peer-reviewed neurotoxicology papers from Chinese authors increased almost 30-fold since 2001. CONCLUSIONS: Despite extensive efforts, neurotoxicity remains a significant public health problem. This provides great challenges and opportunities. We identified 10 significant areas that require major educational, environmental, governmental, and research efforts, as well as attention to public awareness. For example, there is a need to increase efforts to utilize new in vivo and in vitro models, determine the potential neurotoxicity and mechanisms involved in newly emerging pollutants, and examine the effects and mechanisms of mixtures. In the future, we anticipate working with scientists worldwide to accomplish these goals and eliminate, prevent and treat neurotoxicity. CITATION: Cai T, Luo W, Ruan D, Wu YJ, Fox DA, Chen J. 2016. The history, status, gaps, and future directions of neurotoxicology in China. Environ Health Perspect 124:722-732; http://dx.doi.org/10.1289/ehp.1409566. PMID- 26824337 TI - Lentiviral expression of GAD67 and CCK promoter-driven opsins to target interneurons in vitro and in vivo. AB - BACKGROUND: The ability to manipulate the activity of interneurons with optogenetic tools offers the possibility of interfering with diseases caused by altered neuronal inhibition and synchrony, including epilepsy and schizophrenia. To develop vectors for therapeutic approaches, targeting optogenetic constructs to interneurons is therefore a key requirement. We investigated whether the interneuron-specific promoters glutamic acid decarboxylase (GAD)67 and cholecystokinin (CCK) allowed targeted lentiviral delivery of opsins to interneurons as a whole, or specifically CCK+ interneurons. METHODS: We generated lentiviral (LV) plasmids encoding channelrhodopsin (ChR2) and halorhodopsin (NpHR) tagged with fluorophores and driven by GAD67 or CCK promoters. Adeno associated virus (AAV) and LV vectors carrying opsins driven by pyramidal cell promoters were used as controls. We transduced neuronal cultures and rodent brain in vivo, immunostained specimens 6-8 weeks after in vivo injection and 7-14 days after in vitro transduction, and evaluated volume and specificity of expression by confocal microscopy. RESULTS: In vitro, 90% (19/21) of LV-CCK-NpHR2.0-EYFP expressing neurons were CCK+. In vivo, LV-GAD67-ChR2-mCherry was expressed in 2.6% (5/193), LV-GAD67-NpHR2.0-EYFP in approximately 15% (43/279) and LV-CCK NpHR2.0-EYFP in 47% (9/19) of hippocampal GABA+ interneurons. GAD67 vectors expressed in larger volumes than CCK-driven constructs. AAV vector controls achieved the largest expression volumes. CONCLUSIONS: LV-CCK-NpHR2.0-EYFP may be useful for targeting CCK+ interneurons in culture. GAD67/CCK-driven lentiviral constructs are expressed in vivo, although expression is not specific for interneurons. Overall, expression levels are low compared to opsins driven by pyramidal cell promoters. A better understanding of GAD67 and CCK promoter structure or alternative techniques is required to reliably target opsins to interneurons using viral vectors. PMID- 26824339 TI - Confirmed organophosphorus and carbamate pesticide poisonings in South African wildlife (2009-2014). AB - During a six-year period (from January 2009 to December 2014), specimens collected from 344 cases of suspected organophosphorus and carbamate pesticide poisonings in wildlife, including birds, were submitted to the Toxicology Laboratory (ARC-OVI) for analysis. A positive diagnosis was made in 135 (39%) of these cases. The majority of cases were from birds, which included Cape vultures (Gyps coprotheres) and African white-backed vultures (Gyps africanus) and bateleur eagles (Terathopius ecaudatus). In one incident 49 vultures were killed when a farmer intentionally laced carcasses with carbofuran in an attempt to control jackal predation. There were 22 incidents of poisoning in helmeted guineafowl (Numida meleagris). On nine different occasions blue cranes (Anthropoides paradiseus) were poisoned, in one incident 14 birds were reported to have been killed. Over the period of investigation, there were 20 cases of poisoning involving mammalian species, the majority being vervet monkeys (Chlorocebus pygerythrus). The carbamate pesticides were responsible for 57 incidents of poisoning. Aldicarb, carbofuran and methomyl were detected in 26, 18 and 12 cases respectively. The majority of organophosphorus pesticide poisonings were caused by diazinon (n = 19), monocrotophos (n = 13) and methamidophos (n = 10). PMID- 26824338 TI - Lebein, a snake venom disintegrin, suppresses human colon cancer cells proliferation and tumor-induced angiogenesis through cell cycle arrest, apoptosis induction and inhibition of VEGF expression. AB - Lebein, is an heterodimeric disintegrin isolated from Macrovipera lebetina snake venom that was previously characterized as an inhibitor of ADP-induced platelet aggregation. In this study, we investigated the effect of Lebein on the p53 dependent growth of human colon adenocarcinoma cell lines. We found that Lebein significantly inhibited LS174 (p53wt), HCT116 (p53wt), and HT29 (p53mut) colon cancer cell viability by inducing cell cycle arrest through the modulation of expression levels of the tumor suppression factor p53, cell cycle regulating proteins cyclin D1, CDK2, CDK4, retinoblastoma (Rb), CDK1, and cyclin-dependent kinase inhibitors p21 and p27. Interestingly, Lebein-induced apoptosis of colon cancer cells was dependent on their p53 status. Thus, in LS174 cells, cell death was associated with PARP cleavage and the activation of caspases 3 and 8 while in HCT116 cells, Lebein induced caspase-independent apoptosis through increased expression of apoptosis inducing factor (AIF). In LS174 cells, Lebein triggers the activation of the MAPK ERK1/2 pathway through induction of reactive oxygen species (ROS). It also decreased cell adhesion and migration to fibronectin through down regulation of alpha5beta1 integrin. Moreover, Lebein significantly reduced the expression of two angiogenesis stimulators, Vascular Endothelial Growth Factor (VEGF) and Neuropilin 1 (NRP1). It inhibited the VEGF-induced neovascularization process in the quail embryonic CAM system and blocked the development of human colon adenocarcinoma in nude mice. Overall, our work indicates that Lebein may be useful to design a new therapy against colon cancer. (c) 2016 Wiley Periodicals, Inc. PMID- 26824340 TI - Vector-borne diseases of small companion animals in Namibia: Literature review, knowledge gaps and opportunity for a One Health approach. AB - Namibia has a rich history in veterinary health but little is known about the vector-borne diseases that affect companion dogs and cats. The aim of this review is to summarise the existing published and available unpublished literature, put it into a wider geographical context, and explore some significant knowledge gaps. To date, only two filarial pathogens (Dirofilaria repens and Acanthocheilonema dracunculoides) and three tick-borne pathogens (Babesia canis vogeli, Hepatozoon canis and Ehrlichia canis) have been reported. Most studies have focused solely on dogs and cats in the urban Windhoek and surrounding areas, with almost nothing reported in rural farming areas, in either the populous northern regions or the low-income urban areas where animal owners have limited access to veterinary services. With the development of several biomedical training programmes in the country, there is now an excellent opportunity to address zoonotic vector-borne diseases through a One Health approach so as to assess the risks to small companion animals as well as diseases of public health importance. PMID- 26824341 TI - Gallbladder mucocoele: A review. AB - Gallbladder mucocoele (GBM) is an abnormal, intraluminal accumulation of inspissated bile and/or mucous within the gallbladder. Older, small- to medium breed dogs seem to be predisposed, but no sex predilection has been identified. Clinical signs are often non-specific and include vomiting, lethargy, anorexia, abdominal pain, icterus and polyuria-polydipsia. Results of a complete blood count may be unremarkable, but serum biochemistry usually reveals increased liver enzymes. The ultrasonographic appearance is diagnostic and well described in the literature. Surgical intervention for the treatment of GBM remains the therapeutic gold standard, with short- and long-term survival for biliary surgery being 66%. The worst outcome is seen in those dogs requiring cholecystoenterostomy. With GBM becoming an apparently increasingly common cause of extrahepatic biliary disease in canines, it is essential that clinicians become familiar with the current literature pertaining to this condition. Numerous predisposing factors are highlighted in this review article and the role of certain endocrinopathies (e.g. hyperadrenocorticism and hypothyroidism) in the development of GBM is touched upon. Furthermore, the aetiopathogenesis of this disease is discussed with reference to the latest literature. Cholecystectomy remains the treatment of choice, but other options are considered based on a current literature review. PMID- 26824342 TI - Solar keratoma: An atypical case. AB - This case report shows that keratomas can occur in both hind feet of equine patients and should be considered as a diagnosis for long-standing, intermittent lameness localised to the hooves. A Thoroughbred racehorse presented with long standing abscessation of the right hind hoof. Owing to the long-standing nature, the abscess draining tract was surgically explored. A focal mass was found within the solar horn. Histopathology revealed the mass to be a keratoma. A similar mass was removed from the left hind hoof a few months later after similar presenting signs. This case shows that keratomas can occur in more than one hoof within a short period and should be considered a differential diagnosis for long-standing lameness localised to the hoof. PMID- 26824343 TI - Gastrojejunostomy without partial gastrectomy to manage duodenal stenosis in a dog. AB - A nine-year-old female Rottweiler with a history of repeated gastrointestinal ulcerations and three previous surgical interventions related to gastrointestinal ulceration presented with symptoms of anorexia and intermittent vomiting. Benign gastric outflow obstruction was diagnosed in the proximal duodenal area. The initial surgical plan was to perform a pylorectomy with gastroduodenostomy (Billroth I procedure), but owing to substantial scar tissue and adhesions in the area a palliative gastrojejunostomy was performed. This procedure provided a bypass for the gastric contents into the proximal jejunum via the new stoma, yet still allowed bile and pancreatic secretions to flow normally via the patent duodenum. The gastrojejunostomy technique was successful in the surgical management of this case, which involved proximal duodenal stricture in the absence of neoplasia. Regular telephonic followup over the next 12 months confirmed that the patient was doing well. PMID- 26824344 TI - Integrated long non-coding RNA analyses identify novel regulators of epithelial mesenchymal transition in the mouse model of pulmonary fibrosis. AB - Idiopathic pulmonary fibrosis (IPF) is a chronic fatal lung disease characterized by aberrant accumulation of fibroblast population and deposition of extra cellular matrix. Increasing evidence support that epithelial-mesenchymal transition (EMT) of alveolar epithelial cells is a critical process in the pathogenesis of IPF. Although delivery of bleomycin to induce acute lung injury is the most well-studied animal model of pulmonary fibrosis, there is considerable interest to pursue other models to understand the common and/or specific pathological mechanisms. In this study, we established a mouse model of pulmonary injury and progressive interstitial fibrosis via intraperitoneal injection of paraquat, a widely used herbicide known to cause pulmonary fibrosis in human. Using transcriptome sequencing and microarray analysis, we profiled expression of long non-coding RNAs (lncRNAs) and identified 513 up-regulated and 204 down-regulated lncRNAs in paraquat-induced fibrotic lung tissues. Gene ontology analysis revealed that the differentially expressed lncRNAs are implicated in cell differentiation, epithelium morphogenesis and wound healing, pathways closely associated with EMT. Furthermore, we identified the evolutionally conserved target genes of two up-regulated lncRNAs, uc.77 and 2700086A05Rik, as Zeb2 and Hoxa3, respectively, both of which are important modulators of EMT. Consistently, overexpression of uc.77 or 2700086A05Rik in human lung epithelial cells induced EMT as demonstrated by changes in gene and protein expression of various EMT markers and cell morphology. Collectively, our results uncovered a crucial role of lncRNA in the regulation of EMT during lung fibrosis and provide potential avenues for the discovery of novel molecular markers and therapeutic targets for IPF. PMID- 26824347 TI - One Step Forward, Two Steps Back; Xeno-MicroRNAs Reported in Breast Milk Are Artifacts. AB - BACKGROUND: MicroRNAs (miRNAs) are short RNA sequences that guide post transcriptional regulation of gene expression via complementarity to their target mRNAs. Discovered only recently, miRNAs have drawn a lot of attention. Multiple protein complexes interact to first cleave a hairpin from nascent RNA, export it into the cytosol, trim its loop, and incorporate it into the RISC complex which is important for binding its target mRNA. This process works within one cell, but circulating miRNAs have been described suggesting a role in cell-cell communication. MOTIVATION: Viruses and intracellular parasites like Toxoplasma gondii use miRNAs to manipulate host gene expression from within the cellular environment. However, recent research has claimed that a rice miRNA may regulate human gene expression. Despite ongoing debates about these findings and general reluctance to accept them, a recent report claimed that foodborne plant miRNAs pass through the digestive tract, travel through blood to be incorporated by alveolar cells excreting milk. The miRNAs are then said to have some immune related function in the newborn. PRINCIPAL FINDINGS: We acquired the data that supports their claim and performed further analyses. In addition to the reported miRNAs, we were able to detect almost complete mRNAs and found that the foreign RNA expression profiles among samples are exceedingly similar. Inspecting the source of the data helped understand how RNAs could contaminate the samples. CONCLUSION: Viewing these findings in context with the difficulties foreign RNAs face on their route into breast milk and the fact that many identified foodborne miRNAs are not from actual food sources, we can conclude beyond reasonable doubt that the original claims and evidence presented may be due to artifacts. We report that the study claiming their existence is more likely to have detected RNA contamination than miRNAs. PMID- 26824345 TI - Disruption of endosperm development is a major cause of hybrid seed inviability between Mimulus guttatus and Mimulus nudatus. AB - Divergence of developmental mechanisms within populations could lead to hybrid developmental failure, and might be a factor driving speciation in angiosperms. We investigate patterns of endosperm and embryo development in Mimulus guttatus and the closely related, serpentine endemic Mimulus nudatus, and compare them to those of reciprocal hybrid seed. We address whether disruption in hybrid seed development is the primary source of reproductive isolation between these sympatric taxa. M. guttatus and M. nudatus differ in the pattern and timing of endosperm and embryo development. Some hybrid seeds exhibit early disruption of endosperm development and are completely inviable, while others develop relatively normally at first, but later exhibit impaired endosperm proliferation and low germination success. These developmental patterns are reflected in mature hybrid seeds, which are either small and flat (indicating little to no endosperm) or shriveled (indicating reduced endosperm volume). Hybrid seed inviability forms a potent reproductive barrier between M. guttatus and M. nudatus. We shed light on the extent of developmental variation between closely related species within the M. guttatus species complex, an important ecological model system, and provide a partial mechanism for the hybrid barrier between M. guttatus and M. nudatus. PMID- 26824348 TI - Observed Measures of Negative Parenting Predict Brain Development during Adolescence. AB - Limited attention has been directed toward the influence of non-abusive parenting behaviour on brain structure in adolescents. It has been suggested that environmental influences during this period are likely to impact the way that the brain develops over time. The aim of this study was to investigate the association between aggressive and positive parenting behaviors on brain development from early to late adolescence, and in turn, psychological and academic functioning during late adolescence, using a multi-wave longitudinal design. Three hundred and sixty seven magnetic resonance imaging (MRI) scans were obtained over three time points from 166 adolescents (11-20 years). At the first time point, observed measures of maternal aggressive and positive behaviors were obtained. At the final time point, measures of psychological and academic functioning were obtained. Results indicated that a higher frequency of maternal aggressive behavior was associated with alterations in the development of right superior frontal and lateral parietal cortical thickness, and of nucleus accumbens volume, in males. Development of the superior frontal cortex in males mediated the relationship between maternal aggressive behaviour and measures of late adolescent functioning. We suggest that our results support an association between negative parenting and adolescent functioning, which may be mediated by immature or delayed brain maturation. PMID- 26824349 TI - Patterns of Occurrence of Sharks in Sydney Harbour, a Large Urbanised Estuary. AB - Information about spatial and temporal variability in the distribution and abundance of shark-populations are required for their conservation, management and to update measures designed to mitigate human-shark interactions. However, because some species of sharks are mobile, migratory and occur in relatively small numbers, estimating their patterns of distribution and abundance can be very difficult. In this study, we used a hierarchical sampling design to examine differences in the composition of species, size- and sex-structures of sharks sampled with bottom-set longlines in three different areas with increasing distance from the entrance of Sydney Harbour, a large urbanised estuary. During two years of sampling, we obtained data for four species of sharks (Port Jackson, Heterodontus portusjacksoni; wobbegong, Orectolobus maculatus; dusky whaler, Carcharhinus obscurus and bull shark, Carcharhinus leucas). Only a few O. maculatus and C. obscurus were caught, all in the area closest to the entrance of the Harbour. O. maculatus were caught in all seasons, except summer, while C. obscurus was only caught in summer. Heterodontus portusjacksoni were the most abundant species, caught in the entrance location mostly between July to November, when water temperature was below 21.5 degrees C. This pattern was consistent across both years. C. leucas, the second most abundant species, were captured in all areas of Sydney Harbour but only in summer and autumn when water temperatures were above 23 degrees C. This study quantified, for this first time, how different species utilise different areas of Sydney Harbour, at different times of the year. This information has implications for the management of human shark interactions, by enabling creation of education programs to modify human behaviour in times of increased risk of potentially dangerous sharks. PMID- 26824350 TI - Offshore Habitat Preference of Overwintering Juvenile and Adult Black Sea Bass, Centropristis striata, and the Relationship to Year-Class Success. AB - Black sea bass (Centropristis striata) migrations are believed to play a role in overwinter survival and connectivity between juvenile and adult populations. This study investigated oceanographic drivers of winter habitat choice and regional differences between populations of juvenile and adult black sea bass. Trends in cohort strength, as a result of juvenile survival, were also identified. Oceanographic and fisheries survey data were analyzed using generalized additive models. Among the oceanographic variables investigated, salinity was the main driver in habitat selection with an optimal range of 33-35 practical salinity units (PSU) for both juveniles and adults. Preferred temperature ranges varied between juveniles and adults, but held a similar minimum preference of >8 degrees C. Salinity and temperature ranges also differed by regions north and south of Hudson Canyon. Shelf water volume had less of an effect than temperature or salinity, but showed an overall negative relationship with survey catch. The effect of winter conditions on juvenile abundance was also observed across state and federal survey index trends. A lack of correlation observed among surveys in the fall paired with a strong correlation in the spring identifies the winter period as a factor determining year-class strength of new recruits to the population. A rank order analysis of spring indices identified three of the largest year classes occurring during years with reduced shelf water volumes, warmer winter shelf waters, and a 34 PSU isohaline aligned farther inshore. While greater catches of black sea bass in the northwest Atlantic Ocean remain south of Hudson Canyon, the species' range has expanded north in recent years. PMID- 26824351 TI - Modeling Verdict Outcomes Using Social Network Measures: The Watergate and Caviar Network Cases. AB - Modelling criminal trial verdict outcomes using social network measures is an emerging research area in quantitative criminology. Few studies have yet analyzed which of these measures are the most important for verdict modelling or which data classification techniques perform best for this application. To compare the performance of different techniques in classifying members of a criminal network, this article applies three different machine learning classifiers-Logistic Regression, Naive Bayes and Random Forest-with a range of social network measures and the necessary databases to model the verdicts in two real-world cases: the U.S. Watergate Conspiracy of the 1970's and the now-defunct Canada-based international drug trafficking ring known as the Caviar Network. In both cases it was found that the Random Forest classifier did better than either Logistic Regression or Naive Bayes, and its superior performance was statistically significant. This being so, Random Forest was used not only for classification but also to assess the importance of the measures. For the Watergate case, the most important one proved to be betweenness centrality while for the Caviar Network, it was the effective size of the network. These results are significant because they show that an approach combining machine learning with social network analysis not only can generate accurate classification models but also helps quantify the importance social network variables in modelling verdict outcomes. We conclude our analysis with a discussion and some suggestions for future work in verdict modelling using social network measures. PMID- 26824352 TI - Neighbourhood Deprivation and Outcomes of Stop Smoking Support--An Observational Study. AB - BACKGROUND: Rates of smoking and smoking cessation vary with socio-economic status. The objectives were to assess the association between neighbourhood deprivation, completion of treatment to support quit attempts and success of quit attempts-while taking into account other predictors of outcome. METHODS: 555,744 quit attempts supported by English Stop Smoking Services in 2009-2012 were linked to the Index of Multiple Deprivation (IMD) 2010 ranks for the clients' neighbourhood and split into deciles relative to the national IMD. Logistic regressions tested the association between neighbourhood deprivation and completion (4-week follow-up) of treatment and biochemically validated success (expired-air carbon monoxide <10 ppm) while adjusting for demographics and intervention characteristics. Sensitivity analyses assessed subsamples: first supported attempts (n = 364,397), those with recorded cigarette dependence (n = 98,659) and completed treatment (n = 416,436). RESULTS: Higher neighbourhood deprivation was associated with reduced completion (OR(adj) = 0.949, 95% CI: 0.947 to 0.951) and success (OR(adj) = 0.957, 95% CI: 0.955 to 0.959). Results of sensitivity analyses were consistent with those of the main analysis. CONCLUSIONS: Neighbourhood deprivation was associated with small but consistent reductions in completion and success of evidence-based interventions. These associations were not explained by intervention characteristics, demographics or dependence and reduced completion did not fully account for reduced success. PMID- 26824353 TI - Carbapenem-Resistant Bacteria Recovered from Faeces of Dairy Cattle in the High Plains Region of the USA. AB - OBJECTIVE: A study was conducted to recover carbapenem-resistant bacteria from the faeces of dairy cattle and identify the underlying genetic mechanisms associated with reduced phenotypic susceptibility to carbapenems. METHODS: One hundred and fifty-nine faecal samples from dairy cattle were screened for carbapenem-resistant bacteria. Phenotypic screening was conducted on two media containing ertapenem. The isolates from the screening step were characterised via disk diffusion, Modified Hodge, and Carba NP assays. Carbapenem-resistant bacteria and carbapenemase-producing isolates were subjected to Gram staining and biochemical testing to include Gram-negative bacilli. Whole genome sequencing was performed on bacteria that exhibited either a carbapenemase-producing phenotype or were not susceptible to ertapenem and were presumptively Enterobacteriaceae. RESULTS: Of 323 isolates collected from the screening media, 28 were selected for WGS; 21 of which were based on a carbapenemase-producing phenotype and 7 were presumptively Enterobacteriaceae and not susceptible to ertapenem. Based on analysis of WGS data, isolates included: 3 Escherichia coli harbouring blaCMY-2 and truncated ompF genes; 8 Aeromonas harbouring blacphA-like genes; 1 Acinetobacter baumannii harbouring a novel blaOXA gene (blaOXA-497); and 6 Pseudomonas with conserved domains of various carbapenemase-producing genes. CONCLUSIONS: Carbapenem resistant bacteria appear to be rare in cattle. Nonetheless, carbapenem-resistant bacteria were detected across various genera and were found to harbour a variety of mechanisms conferring reduced susceptibility. The development and dissemination of carbapenem-resistant bacteria in livestock would have grave implications for therapeutic treatment options in human medicine; thus, continued monitoring of carbapenem susceptibility among enteric bacteria of livestock is warranted. PMID- 26824354 TI - Curcumin Ameliorates the Reduction Effect of PGE2 on Fibrillar beta-Amyloid Peptide (1-42)-Induced Microglial Phagocytosis through the Inhibition of EP2-PKA Signaling in N9 Microglial Cells. AB - Inflammatory activation of microglia and beta amyloid (Abeta) deposition are considered to work both independently and synergistically to contribute to the increased risk of Alzheimer's disease (AD). Recent studies indicate that long term use of phenolic compounds provides protection against AD, primarily due to their anti-inflammatory actions. We previously suggested that phenolic compound curcumin ameliorated phagocytosis possibly through its anti-inflammatory effects rather than direct regulation of phagocytic function in electromagnetic field exposed N9 microglial cells (N9 cells). Here, we explored the prostaglandin-E2 (PGE2)-related signaling pathway that involved in curcumin-mediated phagocytosis in fibrillar beta-amyloid peptide (1-42) (fAbeta42)-stimulated N9 cells. Treatment with fAbeta42 increased phagocytosis of fluorescent-labeled latex beads in N9 cells. This increase was attenuated in a dose-dependent manner by endogenous and exogenous PGE2, as well as a selective EP2 or protein kinase A (PKA) agonist, but not by an EP4 agonist. We also found that an antagonist of EP2, but not EP4, abolished the reduction effect of PGE2 on fAbeta42-induced microglial phagocytosis. Additionally, the increased expression of endogenous PGE2, EP2, and cyclic adenosine monophosphate (AMP), and activation of vasodilator-stimulated phosphoprotein, cyclic AMP responsive element-binding protein, and PKA were depressed by curcumin administration. This reduction led to the amelioration of the phagocytic abilities of PGE2-stimulated N9 cells. Taken together, these data suggested that curcumin restored the attenuating effect of PGE2 on fAbeta42-induced microglial phagocytosis via a signaling mechanism involving EP2 and PKA. Moreover, due to its immune modulatory effects, curcumin may be a promising pharmacological candidate for neurodegenerative diseases. PMID- 26824355 TI - The GTPase ARF6 Controls ROS Production to Mediate Angiotensin II-Induced Vascular Smooth Muscle Cell Proliferation. AB - High reactive oxygen species (ROS) levels and enhanced vascular smooth muscle cells (VSMC) proliferation are observed in numerous cardiovascular diseases. The mechanisms by which hormones such as angiotensin II (Ang II) acts to promote these cellular responses remain poorly understood. We have previously shown that the ADP-ribosylation factor 6 (ARF6), a molecular switch that coordinates intracellular signaling events can be activated by the Ang II receptor (AT1R). Whether this small GTP-binding protein controls the signaling events leading to ROS production and therefore Ang II-dependent VSMC proliferation, remains however unknown. Here, we demonstrate that in rat aortic VSMC, Ang II stimulation led to the subsequent activation of ARF6 and Rac1, a key regulator of NADPH oxidase activity. Using RNA interference, we showed that ARF6 is essential for ROS generation since in conditions where this GTPase was knocked down, Ang II could no longer promote superoxide anion production. In addition to regulating Rac1 activity, ARF6 also controlled expression of the NADPH oxidase 1 (Nox 1) as well as the ability of the EGFR to become transactivated. Finally, ARF6 also controlled MAPK (Erk1/2, p38 and Jnk) activation, a key pathway of VSMC proliferation. Altogether, our findings demonstrate that Ang II promotes activation of ARF6 to controls ROS production by regulating Rac1 activation and Nox1 expression. In turn, increased ROS acts to activate the MAPK pathway. These signaling events represent a new molecular mechanism by which Ang II can promote proliferation of VSMC. PMID- 26824356 TI - Expression Profile of Cytokines and Enzymes mRNA in Blood Leukocytes of Dogs with Leptospirosis and Its Associated Pulmonary Hemorrhage Syndrome. AB - BACKGROUND: Dogs with leptospirosis show similar organ manifestations and disease course as human patients, including acute kidney injury and pulmonary hemorrhage, making this naturally-occurring infection a good animal model for human leptospirosis. Expression patterns of cytokines and enzymes have been correlated with disease manifestations and clinical outcome in humans and animals. The aim of this study was to describe mRNA expression of pro- and anti-inflammatory mediators in canine leptospirosis and to compare it with other renal diseases to identify patterns characterizing the disease and especially its pulmonary form. METHODOLOGY AND PRINCIPAL FINDINGS: The mRNA abundance of cytokines (IL-1alpha, IL-1beta, IL-8, IL-10, TNF-alpha, TGF-beta) and enzymes (5-LO, iNOS) was measured prospectively in blood leukocytes from 34 dogs with severe leptospirosis and acute kidney injury, including 22 dogs with leptospirosis-associated pulmonary hemorrhages. Dogs with leptospirosis were compared to 14 dogs with acute kidney injury of other origin than leptospirosis, 8 dogs with chronic kidney disease, and 10 healthy control dogs. Canine leptospirosis was characterized by high 5-LO and low TNF-alpha expression compared to other causes of acute kidney injury, although the decreased TNF-alpha expression was also seen in chronic kidney disease. Leptospirosis-associated pulmonary hemorrhage was not characterized by a specific pattern, with only mild changes noted, including increased IL-10 and decreased 5-LO expression on some days in affected dogs. Fatal outcome from pulmonary hemorrhages was associated with low TNF-alpha, high IL-1beta, and high iNOS expression, a pattern possibly expressed also in dogs with other forms of acute kidney injury. CONCLUSION: The patterns of cytokine and enzyme expression observed in the present study indicate a complex pro- and anti-inflammatory response to the infection with leptospires. The recognition of these signatures may be of diagnostic and prognostic relevance for affected individuals and they may indicate options for newer therapies targeting the identified pathways. PMID- 26824358 TI - Correction: Simvastatin Attenuates Oxidative Stress, NF-kappaB Activation, and Artery Calcification in LDLR-/- Mice Fed with High Fat Diet via Down-regulation of Tumor Necrosis Factor-alpha and TNF Receptor 1. PMID- 26824359 TI - A score model for the continuous grading of early allograft dysfunction severity. PMID- 26824357 TI - Unique beta-Glucuronidase Locus in Gut Microbiomes of Crohn's Disease Patients and Unaffected First-Degree Relatives. AB - Crohn's disease, an incurable chronic inflammatory bowel disease, has been attributed to both genetic predisposition and environmental factors. A dysbiosis of the gut microbiota, observed in numerous patients but also in at least one hundred unaffected first-degree relatives, was proposed to have a causal role. Gut microbiota beta-D-glucuronidases (EC 3.2.1.33) hydrolyse beta-D-glucuronate from glucuronidated compounds. They include a GUS group, that is homologous to the Escherichia coli GusA, and a BG group, that is homologous to metagenomically identified H11G11 BG and has unidentified natural substrates. H11G11 BG is part of the functional core of the human gut microbiota whereas GusA, known to regenerate various toxic products, is variably found in human subjects. We investigated potential risk markers for Crohn's disease using DNA-sequence-based exploration of the beta-D-glucuronidase loci (GUS or Firmicute H11G11-BG and the respective co-encoded glucuronide transporters). Crohn's disease-related microbiomes revealed a higher frequency of a C7D2 glucuronide transporter (12/13) compared to unrelated healthy subjects (8/32). This transporter was in synteny with the potential harmful GUS beta-D-glucuronidase as only observed in a Eubacterium eligens plasmid. A conserved NH2-terminal sequence in the transporter (FGDFGND motif) was found in 83% of the disease-related subjects and only in 12% of controls. We propose a microbiota-pathology hypothesis in which the presence of this unique beta-glucuronidase locus may contribute to an increase risk for Crohn's disease. PMID- 26824360 TI - Beyond ROI: Using Value of Investment to Measure Employee Health and Wellness. PMID- 26824361 TI - Association between Dietary Vitamin C Intake and Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study among Middle-Aged and Older Adults. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become one of the most prevalent chronic liver disease all over the world. The objective of this study was to evaluate the association between dietary vitamin C intake and NAFLD. METHOD: Subjects were diagnosed with NAFLD by abdominal ultrasound examination and the consumption of alcohol was less than 40g/day for men or less than 20g/day for women. Vitamin C intake was classified into four categories according to the quartile distribution in the study population: <=74.80 mg/day, 74.81-110.15 mg/day, 110.16-146.06 mg/day, and >=146.07 mg/day. The energy and multi-variable adjusted odds ratio (OR), as well as their corresponding 95% confidence interval (CI), were used to determine the relationship between dietary vitamin C intake and NAFLD through logistic regression. RESULT: The present cross-sectional study included 3471 subjects. A significant inverse association between dietary vitamin C intake and NAFLD was observed in the energy-adjusted and the multivariable model. The multivariable adjusted ORs (95%CI) for NAFLD were 0.69 (95%CI: 0.54 0.89), 0.93 (95%CI: 0.72-1.20), and 0.71 (95%CI: 0.53-0.95) in the second, third and fourth dietary vitamin C intake quartiles, respectively, compared with the lowest (first) quartile. The relative odds of NAFLD was decreased by 0.71 times in the fourth quartile of dietary vitamin C intake compared with the lowest quartile. After stratifying data by sex or the status of obesity, the inverse association remained valid in the male population or non-obesity population, but not in the female population or obesity population. CONCLUSION: There might be a moderate inverse association between dietary vitamin C intake and NAFLD in middle aged and older adults, especially for the male population and non-obesity population. PMID- 26824362 TI - Squalene Inhibits ATM-Dependent Signaling in gammaIR-Induced DNA Damage Response through Induction of Wip1 Phosphatase. AB - Ataxia telangiectasia mutated (ATM) kinase plays a crucial role as a master controller in the cellular DNA damage response. Inhibition of ATM leads to inhibition of the checkpoint signaling pathway. Hence, addition of checkpoint inhibitors to anticancer therapies may be an effective targeting strategy. A recent study reported that Wip1, a protein phosphatase, de-phosphorylates serine 1981 of ATM during the DNA damage response. Squalene has been proposed to complement anticancer therapies such as chemotherapy and radiotherapy; however, there is little mechanistic information supporting this idea. Here, we report the inhibitory effect of squalene on ATM-dependent DNA damage signals. Squalene itself did not affect cell viability and the cell cycle of A549 cells, but it enhanced the cytotoxicity of gamma-irradiation (gammaIR). The in vitro kinase activity of ATM was not altered by squalene. However, squalene increased Wip1 expression in cells and suppressed ATM activation in gammaIR-treated cells. Consistent with the potential inhibition of ATM by squalene, IR-induced phosphorylation of ATM effectors such as p53 (Ser15) and Chk1 (Ser317) was inhibited by cell treatment with squalene. Thus, squalene inhibits the ATM dependent signaling pathway following DNA damage through intracellular induction of Wip1 expression. PMID- 26824365 TI - Novel Therapeutic Approaches in Diabetes. AB - This chapter deals with novel therapeutic approaches, predominantly for type 2 diabetes. Incretin-based therapies utilize the effects of glucagon-like peptide-1 (GLP-1), which stimulates insulin and inhibits glucagon secretion in a glucose dependent manner. Incretin-based therapies comprise injectable GLP-1 receptor agonists and orally active dipeptidyl peptidase-IV inhibitors. Both have a low hypoglycaemia risk. GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, dulaglutide, albiglutide) reduce glycated haemoglobin levels more effectively than oral antidiabetic agents do and lead to weight loss as well as a slight decrease in systolic blood pressure. The most common side effects are nausea and fullness, especially during the start of therapy. Dipeptidyl peptidase IV inhibitors (alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin) are not inferior to sulfonylureas, causing significantly less hypoglycaemia and not inducing weight gain. Specific adverse effects have not been discovered yet, and cardiovascular safety has been demonstrated in respective studies. Sodium glucose transporter-2 inhibitors (dapagliflozin, canagliflozin, empagliflozin) were introduced recently. They block the tubular reabsorption of glucose in the kidney and represent an insulin-independent mode of action, with low hypoglycaemia risk and allowing weight loss. The most common side effects are genital and urinary tract infections. Other novel drugs in development (G-protein coupled receptor agonists, interleukin-1 antagonists) are also described. PMID- 26824363 TI - Effect of Leptin Replacement on PCSK9 in ob/ob Mice and Female Lipodystrophic Patients. AB - Leptin treatment has beneficial effects on plasma lipids in patients with lipodystrophy, but the underlying mechanism is unknown. Proprotein convertase subtilisin/kexin type 9 (PCSK9) decreases low-density lipoprotein (LDL) clearance, promotes hypercholesterolemia, and has recently emerged as a novel therapeutic target. To determine the effect of leptin on PCSK9, we treated male and female ob/ob mice with leptin for 4 days via sc osmotic pumps (~24 MUg/d). Leptin reduced body weight and food intake in all mice, but the effects of leptin on plasma PCSK9 and lipids differed markedly between the sexes. In male mice, leptin suppressed PCSK9 but had no effect on plasma triglycerides or cholesterol. In female mice, leptin suppressed plasma triglycerides and cholesterol but had no effect on plasma PCSK9. In parallel, we treated female lipodystrophic patients (8 females, ages 5-23 y) with sc metreleptin injections (~4.4 mg/d) for 4-6 months. In this case, leptin reduced plasma PCSK9 by 26% (298 +/- 109 vs 221 +/- 102 ng/mL; n = 8; P = .008), and the change in PCSK9 was correlated with a decrease in LDL cholesterol (r(2) = 0.564, P = .03). In summary, in leptin-deficient ob/ob mice, the effects of leptin on PCSK9 and plasma lipids appeared to be independent of one another and strongly modified by sex. On the other hand, in lipodystrophic females, leptin treatment reduced plasma PCSK9 in parallel with LDL cholesterol. PMID- 26824364 TI - Estradiol Restrains Prepubertal Gonadotropin Secretion in Female Mice via Activation of ERalpha in Kisspeptin Neurons. AB - Elimination of estrogen receptoralpha (ERalpha) from kisspeptin (Kiss1) neurons results in premature LH release and pubertal onset, implicating these receptors in 17beta-estradiol (E2)-mediated negative feedback regulation of GnRH release during the prepubertal period. Here, we tested the dependency of prepubertal negative feedback on ERalpha in Kiss1 neurons. Prepubertal (postnatal d 14) and peripubertal (postnatal d 34) wild-type (WT) and Kiss1 cell-specific ERalpha knockout (KERalphaKO) female mice were sham operated or ovariectomized and treated with either vehicle- or E2-containing capsules. Plasma and tissues were collected 2 days after surgery for analysis. Ovariectomy increased LH and FSH levels, and E2 treatments completely prevented these increases in WT mice of both ages. However, in prepubertal KERalphaKO mice, basal LH levels were elevated vs WT, and both LH and FSH levels were not further increased by ovariectomy or affected by E2 treatment. Similarly, Kiss1 mRNA levels in the medial basal hypothalamus, which includes the arcuate nucleus, were suppressed with E2 treatment in ovariectomized prepubertal WT mice but remained unaffected by any treatment in KERalphaKO mice. In peripubertal KERalphaKO mice, basal LH and FSH levels were not elevated vs WT and were unaffected by ovariectomy or E2. In contrast to our previous findings in adult animals, these results demonstrate that suppression of gonadotropins and Kiss1 mRNA by E2 in prepubertal animals depends upon ERalpha activation in Kiss1 neurons. Our observations are consistent with the hypothesis that these receptors play a critical role in restraining GnRH release before the onset and completion of puberty. PMID- 26824366 TI - Genetic Defects of the beta-Cell That Cause Diabetes. AB - Individuals with higher-than-normal blood sugar levels used to be diagnosed as having either type 1 or type 2 diabetes. We now know that a wide range of different factors can cause diabetes, including single gene defects, which account for at least 1% of all diabetes cases and up to 4% of cases in the pediatric population. However, misdiagnosis remains common due to the considerable clinical overlap between the different diabetes forms. Monogenic diabetes onset can occur shortly after birth, as observed in neonatal diabetes mellitus, or any time later in life. The present chapter outlines the genes currently known to be involved in monogenic diabetes. Some of these genes are involved in beta-cell development, with mutations often leading to a decreased beta-cell number, while others play important roles in beta-cell function and maintenance. Monogenic forms of autoimmune diabetes and epigenetic causes will also be discussed. A genetic diagnosis may influence treatment choice and prognosis determination and may also lead to family counseling. Genetic screening using next-generation sequencing is becoming more practical as it becomes increasingly accessible and less expensive. PMID- 26824368 TI - Posterior Cruciate Ligament Retention versus Posterior Stabilization for Total Knee Arthroplasty: A Meta-Analysis. AB - INTRODUCTION: Although being debated for many years, the superiority of posterior cruciate-retaining (CR) total knee arthroplasty (TKA) and posterior-stabilized (PS) TKA remains controversial. We compare the knee scores, post-operative knee range of motion (ROM), radiological outcomes about knee kinematic and complications between CR TKA and PS TKA. METHODS: Literature published up to August 2015 was searched in PubMed, Embase and Cochrane databases, and meta analysis was performed using the software, Review Manager version 5.3. RESULTS: Totally 14 random control trials (RCTs) on this topic were included for the analysis, which showed that PS and CR TKA had no significant difference in Knee Society knee Score (KSS), pain score (KSPS), Hospital for Special Surgery score (HSS), kinematic characteristics including postoperative component alignment, tibial posterior slope and joint line, and complication rate. However, PS TKA is superior to CR TKA regarding post-operative knee range of motion (ROM) [Random Effect model (RE), Mean Difference (MD) = -7.07, 95% Confidential Interval (CI) 10.50 to -3.65, p<0.0001], improvement of ROM (Fixed Effect model (FE), MD = 5.66, 95% CI -10.79 to -0.53, p = 0.03) and femoral-tibial angle [FE, MD = 0.85, 95% CI 0.46 to 1.25, p<0.0001]. CONCLUSIONS: There are no clinically relevant differences between CR and PS TKA in terms of clinical, functional, radiological outcome, and complications, while PS TKA is superior to CR TKA in respects of ROM, while whether this superiority matters or not in clinical practice still needs further investigation and longer follow-up. PMID- 26824370 TI - Do tumor and ventricular volume predict the need for postresection shunting in colloid cyst patients? AB - OBJECTIVE Many colloid cyst patients present with obstructive hydrocephalus that resolves after resection of the cyst. However, a proportion of patients with these cysts will require cerebrospinal fluid shunting after tumor resection, despite resolution of the obstruction at the foramina of Monro. The goal of this study was to determine if colloid cyst size or preoperative ventricular volume predicted the need for postresection shunting. METHODS In a retrospective study design, ICD-9 codes 742.2 (colloid cyst) and 348.0 (brain cyst) were used to identify patients who had undergone resection of a colloid cyst at the University of Florida over the last 20 years. Preoperative imaging (CT or MRI) with a stereotactic software program developed at the University of Florida was used to measure volumes of the colloid cyst and the lateral ventricles. The relationships among ventricular volume, colloid cyst volume, and postoperative shunting were analyzed. RESULTS The number of patients included in the study was 67, and their mean age was 37.7 years. Forty percent of the patients were female. Overall, 49.2% of the patients had a transcallosal approach, 35.8% a transcortical approach, and 14.9% an endoscope-assisted surgery. Mean preoperative ventricular volume was 76.5 cc in patients who never received a ventriculoperitoneal shunt (VPS) and 98.1 cc in those who were eventually treated with a VPS (p = 0.305). Patients with a postoperative VPS had an initial mean colloid cyst volume of 1.8 cc compared with 0.9 cc in patients without a VPS postoperatively (p = 0.019). Patients with colloid cysts larger than 0.6 cc (1-cm diameter) had a 12.8 increased odds of needing a VPS postoperatively (95% CI 1.81-275). CONCLUSIONS Larger colloid cysts are associated with an increased need for postresection shunting independent of preoperative ventricular size. Prospective studies of patients with colloid cysts are necessary to further identify risks of permanent hydrocephalus. PMID- 26824369 TI - The Simpson grading revisited: aggressive surgery and its place in modern meningioma management. AB - OBJECTIVE Recent advances in radiotherapy and neuroimaging have called into question the traditional role of aggressive resections in patients with meningiomas. In the present study the authors reviewed their institutional experience with a policy based on maximal safe resections for meningiomas, and they analyzed the impact of the degree of resection on functional outcome and progression-free survival (PFS). METHODS The authors retrospectively analyzed 901 consecutive patients with primary meningiomas (716 WHO Grade I, 174 Grade II, and 11 Grade III) who underwent resections at the University Hospital of Bonn between 1996 and 2008. Clinical and treatment parameters as well as tumor characteristics were analyzed using standard statistical methods. RESULTS The median follow-up was 62 months. PFS rates at 5 and 10 years were 92.6% and 86.0%, respectively. Younger age, higher preoperative Karnofsky Performance Scale (KPS) score, and convexity tumor location, but not the degree of resection, were identified as independent predictors of a good functional outcome (defined as KPS Score 90 100). Independent predictors of PFS were degree of resection (Simpson Grade I vs II vs III vs IV), MIB-1 index (< 5% vs 5%-10% vs >10%), histological grade (WHO I vs II vs III), tumor size (<= 6 vs > 6 cm), tumor multiplicity, and location. A Simpson Grade II rather than Grade I resection more than doubled the risk of recurrence at 10 years in the overall series (18.8% vs 8.5%). The impact of aggressive resections was much stronger in higher grade meningiomas. CONCLUSIONS A policy of maximal safe resections for meningiomas prolongs PFS and is not associated with increased morbidity. PMID- 26824371 TI - Real-time intraoperative monitoring of brainstem auditory evoked potentials during microvascular decompression for hemifacial spasm. AB - OBJECTIVE The aim of this study was to define a new protocol for intraoperative monitoring (IOM) of brainstem auditory evoked potentials (BAEPs) during microvascular decompression (MVD) surgery to treat hemifacial spasm (HFS) and to evaluate the usefulness of this new protocol to prevent hearing impairment. METHODS To define the optimal stimulation rate, estimate the number of trials to be averaged, and identify useful warning criteria in IOM of BAEPs, the authors performed a preliminary study of 13 patients with HFS in 2010. They increased the stimulation rate from 10.1 Hz/sec to 100.1 Hz/sec by 10-Hz increments, and they elevated the average time from 100 times to 1000 times by 100-unit increments at a fixed stimulus rate of 43.9 Hz. After defining the optimal stimulation rate and the number of trials that needed to be averaged for IOM of BAEPs, they also identified the useful warning criteria for this protocol for MVD surgery. From January to December 2013, 254 patients with HFS underwent MVD surgery following the new IOM of BAEPs protocol. Pure-tone audiometry and speech discrimination scoring were performed before surgery and 1 week after surgery. To evaluate the usefulness of the new protocol, the authors compared the incidence of postoperative hearing impairment with the results from the group that underwent MVD surgery prior to the new protocol. RESULTS Through a preliminary study, the authors confirmed that it was possible to obtain a reliable wave when using a stimulation rate of 43.9 Hz/sec and averaging 400 trials. Only a Wave V amplitude loss > 50% was useful as a warning criterion when using the new protocol. A reliable BAEP could be obtained in approximately 9.1 seconds. When the new protocol was used, 2 patients (0.8%) showed no recovery of Wave V amplitude loss > 50%, and only 1 of those 2 patients (0.39%) ultimately had postoperative hearing impairment. When compared with the outcomes in the pre-protocol group, hearing impairment incidence decreased significantly among patients who underwent surgery with the new protocol (0.39% vs 4.02%, p = 0.002). There were no significant differences between the 2 surgery groups regarding other complications, including facial palsy, sixth cranial nerve palsy, and vocal cord palsy. CONCLUSIONS There was a significant decrease in postoperative hearing impairment after MVD for HFS when the new protocol for IOM of BAEPs was used. Real-time IOM of BAEPs, which can obtain a reliable BAEP in less than 10 seconds, is a successful new procedure for preventing hearing impairment during MVD surgery for HFS. PMID- 26824372 TI - Obituary: John F. Mullan, MD, 1925-2015: neurosurgery's modern statesman. PMID- 26824373 TI - Focal cerebral ischemic tolerance and change in blood-brain barrier permeability after repetitive pure oxygen exposure preconditioning in a rodent model. AB - OBJECTIVE The goal of this study was to demonstrate that repetitive pure oxygen exposure preconditioning (O2PC) for 8 hours per day for 3 or 7 days, a practicable preconditioning for clinical use, is able to induce cerebral ischemic tolerance (IT) and further clarify the accompanying changes in the blood-brain barrier (BBB) that may be involved. METHODS A total of 68 adult male Sprague Dawley rats and eight 1-day-old rat pups were used in this study. The adult rats were exposed to pure O2 (38 rats) 8 hours a day for 3 or 7 days or to room air (in an identical setup) for 8 hours a day for 7 days as controls (30 rats). Arterial O2 tension (PaO2) was measured in 6 rats exposed to O2 and 3 controls. Focal cerebral ischemia was elicited by middle cerebral artery occlusion (MCAO) in 37 rats, of which 21 had been exposed to pure O2 for 3 or 7 days and 16 to room air for 7 days as controls. Neurological behavior was scored with the Garcia score in 15 MCAO rats, of which 10 had been exposed to pure O2 for 3 or 7 days and 5 to room air for 7 days as controls, and cerebral infarct volumes were assessed with TTC (2,3,5-triphenyltetrazolium chloride) staining in 10 rats (5 from each group) after 7 days of exposure. Formamide-extraction method was used to detect leakage of Evans blue (EB) dye in 7 rats exposed to pure O2 for 7 days and 7 exposed to room air for 7 days. Fluorescence microscopy was used to analyze the leaked EB in the nonischemic areas of 4 rats exposed to pure O2 for 7 days and 4 exposed to room air for 7 days before MCAO and the brain of the rats that had not been subjected to MCAO. Astrocyte changes associated with O2PC were evaluated by means of fluorescence microscopy and electron microscopy in 14 rats that were exposed to the same O2 or control conditions as the MCAO rats but without MCAO. Astrocytes were also obtained from 8 rat pups and cultured; levels of AQP4 and VEGF were detected by Western blot and ELISA in cells with and without O2 treatment. RESULTS A significant increase in PaO2 was seen after O2PC. The neurological score was significantly increased in the O2PC groups (10.6 +/- 0.6 in the 3-day O2PC group, p < 0.05; 12 +/- 0.84 in the 7-day O2PC group, p < 0.05) compared with the control group (7 +/- 0.55). The ratio of cerebral infarct volume to contralateral cerebral hemisphere volume was significantly lower in the O2PC group than in the control group (0.204 +/- 0.03 vs 0.48 +/- 0.05, p < 0.05). The amount of leaked EB in the ischemic cerebral hemisphere was also lower in the O2-treated rats than in controls (7.53 +/- 1.4 vs 11.79 +/- 3.3 MUg EB/g brain weight, p < 0.05). However, fluorescence microscopy showed significantly greater BBB permeability in the nonischemic areas in the O2PC group than in controls (p < 0.05). More red fluorescence could be observed in the nonischemic areas in both the ipsilateral and contralateral sides of the ischemic brain in the O2PC animals than in the nonischemic areas in the corresponding sides of the controls. Further investigation of the effect of the O2PC itself on the BBB of rats that were not subjected to MCAO showed that there was no EB leakage in the brain parenchyma in the rats exposed to room air, but some red fluorescence patches were noticed in the normal brain from the rats in the O2PC group. Astrocytes, including those from areas around the BBB, were activated in the O2PC group. Levels of both aquaporin 4 (AQP4) and vascular endothelial growth factor (VEGF) were significantly increased in cultured astrocytes after O2PC. CONCLUSIONS These findings suggest that O2PC is able to induce IT, which makes it a strong candidate for clinical use. Moreover, O2PC can also promote BBB opening, which may contribute to the induction of IT as well as representing a possible strategy for promoting drug transportation into the CNS. Activated astrocytes are likely to be involved in these processes through astrocyte-derived factors, such as AQP4 and VEGF. PMID- 26824374 TI - Dissecting pseudoaneurysms: predictors of symptom occurrence, enlargement, clinical outcome, and treatment. AB - OBJECTIVE Dissection of the carotid and vertebral arteries can result in the development of aneurysmal dilations. These dissecting pseudoaneurysms can enlarge and cause symptoms. The objective of this study is to provide insight into the progression of dissecting pseudoaneurysms and the treatments required to manage them. METHODS A review of the electronic medical records was conducted to detect patients with carotid and vertebral artery dissection. An imaging review was conducted to identify patients with dissecting pseudoaneurysms. One hundred twelve patients with 120 dissecting pseudoaneurysms were identified. Univariate and multivariate analyses were conducted to assess the factors associated with undergoing further interventions other than medical treatment, pseudoaneurysm enlargement, pseudoaneurysms resulting in ischemic and nonischemic symptoms, and clinical outcome. RESULTS Overall, 18.3% of pseudoaneurysms were intracranial and 81.7% were extracranial, and the average size was 7.3 mm. The mean follow-up time was 29.3 months; 3.3% of patients had a recurrent transient ischemic attack, no patients had a recurrent stroke, and 14.2% of patients had recurrence of nonischemic symptoms (headache, neck pain, Horner syndrome, or cranial nerve palsy). Follow-up imaging demonstrated that 13.8% of pseudoaneurysms had enlarged, 30.2% had healed, and 56% had remained stable. In total, 20.8% of patients had an intervention other than medical treatment. Interventions included stenting, coiling, flow diversion, and clipping. Predictors of intervention included increasing size, size > 10 mm, location in the C2 (petrous) segment of the internal carotid artery (ICA), younger age, hyperlipidemia, pseudoaneurysm enlargement, and any symptom development. Significant predictors of enlargement included smoking, history of trauma, C2 location, hyperlipidemia, and larger initial pseudoaneurysm size. Predictors of pseudoaneurysm resulting in recurrent ischemic and nonischemic symptoms included increasing size and location in the petrous segment of the ICA. Smoking was a predictor of unfavorable outcome. CONCLUSIONS Dissecting pseudoaneurysms have a benign course and most will not cause symptoms or enlarge on follow-up. Medical treatment can be a sufficient, initial treatment for dissecting pseudoaneurysms. PMID- 26824375 TI - The cochlea in skull base surgery: an anatomy study. AB - OBJECTIVE The object of this study was to examine the relationships of the cochlea as a guide for avoiding both cochlear damage with loss of hearing in middle fossa approaches and injury to adjacent structures in approaches directed through the cochlea. METHODS Twenty adult cadaveric middle fossae were examined using magnifications of *3 to *40. RESULTS The cochlea sits below the floor of the middle fossa in the area between and below the labyrinthine segment of the facial nerve and greater petrosal nerve (GPN) and adjacent to the lateral genu of the petrous carotid. Approximately one-third of the cochlea extends below the medial edge of the labyrinthine segment of the facial nerve, geniculate ganglion, and proximal part of the GPN. The medial part of the basal and middle turns are the parts at greatest risk in drilling the floor of the middle fossa to expose the nerves in middle fossa approaches to the internal acoustic meatus and in anterior petrosectomy approaches. Resection of the cochlea is used selectively in extending approaches through the mastoid toward the lateral edge of the clivus and front of the brainstem. CONCLUSIONS An understanding of the location and relationships of the cochlea will reduce the likelihood of cochlear damage with hearing loss in approaches directed through the middle fossa and reduce the incidence of injury to adjacent structures in approaches directed through the cochlea. PMID- 26824376 TI - Increased incidence of subarachnoid hemorrhage during cold temperatures and influenza epidemics. AB - OBJECTIVE This study investigated whether the increased incidence of aneurysmal subarachnoid hemorrhage (SAH) in winter is related to temperature or increased incidence of influenza. Such relationships may elucidate the pathogenesis of intracranial aneurysm rupture. METHODS A nationwide sample of 18,714 patients with SAH was linked with weekly temperature and influenza-like illness consultation data. Poisson regression analyses were used to calculate incidence density ratios (IDRs) with corresponding 95% CIs for the association of SAH incidence with temperature and influenza epidemics; IDRs were adjusted for study year (aIDR). In addition, SAH incidence data from 30 European population-based studies were linked with daily temperature data from the European Climate Assessment. RESULTS The aIDR for SAH during influenza epidemics was 1.061 (95% CI 1.022-1.101) in the univariable and 1.030 (95% CI 0.989-1.074) in the multivariable analysis. This association declined gradually during the weeks after epidemics. Per 1 degrees C temperature drop, the aIDR was 1.005 (95% CI 1.003-1.008) in the univariable and 1.004 (95% CI 1.002-1.007) in the multivariable analysis. In the European population-based studies, the IDR was 1.143 (95% CI 1.129-1.157) per 1 degrees C temperature drop. CONCLUSIONS The incidence of SAH is increased during cold temperatures and epidemic influenza. Future studies with individual patient data are needed to investigate causality between temperature or influenza and SAH. PMID- 26824377 TI - Idiopathic normal pressure hydrocephalus: diagnostic and predictive value of clinical testing, lumbar drainage, and CSF dynamics. AB - OBJECTIVE The aim of the study was to analyze the diagnostic and predictive values of clinical tests, CSF dynamics, and intracranial pulsatility tests, compared with external lumbar drainage (ELD), for shunt response in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS Sixty-eight consecutive patients with suspected iNPH were prospectively evaluated. Preoperative assessment included clinical tests, overnight intracranial pressure (ICP) monitoring, lumbar infusion test (LIFT), and ELD for 24-72 hours. Simple and multiple linear regression analyses were conducted to identify predictive parameters concerning the outcome after shunt therapy. RESULTS Positive response to ELD correctly predicted improvement after CSF diversion in 87.9% of the patients. A Mini-Mental State Examination (MMSE) value below 21 was associated with nonresponse after shunt insertion (specificity 93%, sensitivity 67%). Resistance to outflow of CSF (ROut) > 12 mm Hg/ml/min was false negative in 21% of patients. Intracranial pulsatility parameters yielded different results in various parameters (correlation coefficient between pulse amplitude and ICP, slow wave amplitude, and mean ICP) but did not correlate to outcome. In multiple linear regression analysis, a calculation of presurgical MMSE versus the value after ELD, ROut, and ICP amplitude quotient during LIFT was significantly associated with outcome (p = 0.04). CONCLUSIONS Despite a multitude of invasive tests, presurgical clinical testing and response to ELD yielded the best prediction for improvement of symptoms following surgery. The complication rate of invasive testing was 5.4%. Multiple and simple linear regression analyses indicated that outcome can only be predicted by a combination of parameters, in accordance with a multifactorial pathogenesis of iNPH. PMID- 26824378 TI - Utility of arterial spin labeling perfusion magnetic resonance imaging in prediction of angiographic vascularity of meningiomas. AB - OBJECTIVE Arterial spin labeling perfusion-weighted imaging (ASL-PWI) enables quantification of tissue perfusion without contrast media administration. The aim of this study was to explore whether cerebral blood flow (CBF) from ASL-PWI can reliably predict angiographic vascularity of meningiomas. METHODS Twenty-seven patients with intracranial meningiomas, who had undergone preoperative ASL-PWI and digital subtraction angiography prior to resection, were included. Angiographic vascularity was assessed using a 4-point grading scale and meningiomas were classified into 2 groups: low vascularity (Grades 0 and 1; n = 11) and high vascularity (Grades 2 and 3; n = 16). Absolute CBF, measured at the largest section of the tumor, was normalized to the contralateral gray matter. Correlation between the mean normalized CBF (nCBF) and angiographic vascularity was determined and the mean nCBF values of the 2 groups were compared. Diagnostic performance of the nCBF for differentiating between the 2 groups was assessed. RESULTS The nCBF had a significant positive correlation with angiographic vascularity (rho = 0.718; p < 0.001). The high-vascularity group had a significantly higher nCBF than the low-vascularity group (3.334 +/- 2.768 and 0.909 +/- 0.468, respectively; p = 0.003). At the optimal nCBF cutoff value of 1.733, sensitivity and specificity for the differential diagnosis of the 2 groups were 69% (95% CI 41%-89%) and 100% (95% CI 72%-100%), respectively. The area under the receiver operating characteristic curve was 0.875 (p < 0.001). CONCLUSIONS ASL-PWI may provide a reliable and noninvasive means of predicting angiographic vascularity of meningiomas. It may thus assist in selecting potential candidates for preoperative digital subtraction angiography and embolization in clinical practice. PMID- 26824379 TI - Stability of hearing preservation and regeneration capacity of the cochlear nerve following vestibular schwannoma surgery via a retrosigmoid approach. AB - OBJECTIVE The purpose of this research was to examine the stability of long-term hearing preservation and the regeneration capacity of the cochlear nerve following vestibular schwannoma (VS) surgery in a prospective study. METHODS A total of 112 patients were recruited for a randomized multicenter trial between January 2010 and April 2012 to investigate the efficacy of prophylactic nimodipine treatment versus no prophylactic nimodipine treatment in VS surgery. For the present investigation, both groups were pooled to compare hearing abilities in the early postoperative course and 1 year after the surgery. Hearing was examined using pure-tone audiometry with speech discrimination, which was performed preoperatively, in the early postoperative course, and 12 months after surgery and was subsequently classified by an independent otorhinolaryngologist using the Gardner-Robertson classification system. RESULTS Hearing abilities at 2 time points were compared by evaluation in the early postoperative course and 1 year after surgery in 102 patients. The chi-square test showed a very strong association between the 2 measurements in all 102 patients (p < 0.001) and in the subgroup of 66 patients with a preserved cochlear nerve (p < 0.001). CONCLUSIONS There is no significant change in cochlear nerve function between the early postoperative course and 1 year after VS surgery. The result of hearing performance, as evaluated by early postoperative audiometry after VS surgery, seems to be a reliable prognosticator for future hearing ability. Clinical trial registration nos.: 2009-012088-32 ( clinicaltrialsregister.eu ) and DRKS 00000328 ("AkNiPro," drks-neu.uniklinik-freiburg.de/drks_web/ ). PMID- 26824380 TI - Gamma Knife radiosurgery in the treatment of abducens nerve schwannomas: a retrospective study. AB - OBJECTIVE Of the intracranial schwannomas, those arising from the vestibular nerves are the most common. Abducens nerve (AN) schwannomas are very rare, and there is limited literature on their optimal management. Therapeutic options include surgery and/or stereotactic radiosurgery. The aim of this study was to evaluate the role of Gamma Knife radiosurgery (GKRS) in these sixth cranial nerve (CN) schwannomas. METHODS The authors performed a retrospective analysis of patients who had undergone GKRS for intracranial tumors at their institute in the period from 2003 to 2010. Inclusion criteria were as follows: isolated AN paresis on presentation, a lesion along the course of the sixth CN, and imaging features characteristic of a schwannoma. Patients with other CN deficits and neurofibromatosis Type 2 were excluded. Symptomatic improvement was defined as the resolution of or an improvement in diplopia noted on a subjective basis or as an improvement in lateral eyeball excursion noted objectively on follow-up. A reduction in tumor volume by at least 20%, as noted by comparing the pre- and post-GKRS images, was deemed significant. RESULTS Six patients with a mean age of 37.1 years (range 17-55 years) underwent primary GKRS. There were 2 prepontine cistern, 3 cavernous sinus, and 1 cisterno-cavernous tumor. The mean duration of symptoms was 6.1 months (range 3-12 months). The mean tumor volume was 3.3 cm3 (range 1.5-4.8 cm3). The mean tumor margin radiation dose was 12.5 Gy (range 12 14 Gy), while the median margin dose was 12 Gy (50% isodose line). The median number of isocenters used was 5 (range 4-8). The brainstem received an average 8.35-Gy radiation dosage (range 5.5-11 Gy). The mean follow-up duration was 44.3 months (range 24-78 months). Symptoms remained stable in 1 patient, improved in 3, and resolved in 2 (total improvement 83%). Magnetic resonance imaging at the last follow-up showed a stable tumor size in 3 patients (50%) and a reduction in the other 3. Thus, the tumor control rate achieved was 100%. No new CN deficits were noted. CONCLUSIONS Abducens nerve schwannomas are rare intracranial tumors. They can be cavernous, cisternal, or cisterno-cavernous in location. Excellent tumor control rates and symptomatic improvement can be achieved with GKRS, which appears to be a safe and effective, minimally invasive modality for the treatment of such lesions. Therefore, it is reasonable to consider GKRS as the initial treatment of choice for this rare pathology. Long-term follow-up will be essential for further recommendations. PMID- 26824381 TI - Letter to the Editor: Sensitivity and specificity levels reported in the TBI literature. PMID- 26824382 TI - Very late ischemic complications in flow-diverter stents: a retrospective analysis of a single-center series. AB - OBJECTIVE The authors evaluate the rate and discuss the pathomechanisms of very late (>= 4-month) ischemic complications after flow-diverter stent (FDS) placement for intracranial aneurysms. METHODS The authors retrospectively reviewed the clinical data of the patients treated at Pitie-Salpetriere Hospital between January 2010 and September 2014, who underwent FDS placement for intracranial aneurysm. The patients received dual-antiplatelet therapy (clopidogrel and aspirin) 5 days before and 3-6 months after the procedure and then aspirin alone for 6-9 months. An ischemic complication was defined as a sudden focal neurological deficit documented on diffusion-weighted images. RESULTS Eighty-six consecutive patients were included. Three (3.5%) patients treated with the Pipeline embolization device experienced a delayed acute ischemic stroke (2 cases of perforator/side-wall branch infarction and 1 case of thromboembolic stroke) with an average delay of 384 days (4 months, 20 months, and 13 months, respectively). The aneurysm locations were the left superior cerebellar artery, the right anterior choroid artery, and the left internal carotid artery (paraclinoid segment), respectively. The complications occurred after the patients had completed the antiaggregation protocol, except for Patient 1, who was receiving aspirin alone because of a spontaneous hematoma. At the acute phase, no in-stent thromboses were found on digital subtraction angiography. In Patient 2, the treated anterior choroid artery was occluded 20 months after the procedure. In Patient 3, a focal stenosis (approximately 40%) of the distal aspect of the FDS, probably caused by intimal hyperplasia, was seen. CONCLUSIONS Very late ischemic complications after FDS treatment were observed in 3.5% of the cases in the authors' series, some of which occurred as late as more than 1 year after placement. PMID- 26824384 TI - Cost-Effectiveness of Immunotherapy in the Treatment of Seasonal Allergic Rhinitis: Identifying Product-Specific Parameters of Relevance for Health Care Decision-Makers and Clinicians. AB - Pharmacotherapy is widely used to manage allergic rhinitis (AR), but often does not adequately control symptoms. Allergy immunotherapy (AIT) should be considered for patients who are not adequately controlled on symptomatic treatment. AIT is gaining attention because of its potential to improve symptom relief and quality of life, and to provide sustained effect after the end of treatment by modifying the course of disease. However, evidence of efficacy needs to be shown for each individual AIT product, based on state-of-the-art studies. The majority of products cannot truly claim efficacy and disease-modifying potential, as evidence of such an effect from robust randomized double-blind, placebo-controlled long term trials is lacking. The potential of a specific immunotherapy product should be evaluated against four levels of benefit defined by the European Medicines Agency (EMA) guideline on clinical development of AIT products. These clearly distinguish between efficacy of symptom relief in the first year, efficacy over 2 3 treatment years, sustained efficacy and disease modification treatment ends, and sustained absence of allergic symptoms in posttreatment years. The clinician's choice of a specific AIT product should take the level of evidence and risk/benefit into account, as the patient's quality of life and the product's potential long-term effect are important components of its overall cost effectiveness. Without evidence of maintained clinical benefit and disease modification after the end of treatment, claims of long-term economic benefit of specific AIT products cannot be justified. This paper discusses the evidence that is essential for critical evaluation of product claims in health economic analysis comparing AIT products. PMID- 26824385 TI - Potential of laryngeal muscle regeneration using induced pluripotent stem cell derived skeletal muscle cells. AB - Conclusion Induced pluripotent stem (iPS) cells may be a new potential cell source for laryngeal muscle regeneration in the treatment of vocal fold atrophy after recurrent laryngeal nerve paralysis. Objectives Unilateral vocal fold paralysis can lead to degeneration, atrophy, and loss of force of the thyroarytenoid muscle. At present, there are some treatments such as thyroplasty, arytenoid adduction, and vocal fold injection. However, such treatments cannot restore reduced mass of the thyroarytenoid muscle. iPS cells have been recognized as supplying a potential resource for cell transplantation. The aim of this study was to assess the effectiveness of the use of iPS cells for the regeneration of laryngeal muscle through the evaluation of both in vitro and in vivo experiments. Methods Skeletal muscle cells were generated from tdTomato-labeled iPS cells using embryoid body formation. Differentiation into skeletal muscle cells was analyzed by gene expression and immunocytochemistry. The tdTomato-labeled iPS cell-derived skeletal muscle cells were transplanted into the left atrophied thyroarytenoid muscle. To evaluate the engraftment of these cells after transplantation, immunohistochemistry was performed. Results The tdTomato-labeled iPS cells were successfully differentiated into skeletal muscle cells through an in vitro experiment. These cells survived in the atrophied thyroarytenoid muscle after transplantation. PMID- 26824383 TI - Factors Associated with Influenza Vaccination of Hospitalized Elderly Patients in Spain. AB - Vaccination of the elderly is an important factor in limiting the impact of influenza in the community. The aim of this study was to investigate the factors associated with influenza vaccination coverage in hospitalized patients aged >= 65 years hospitalized due to causes unrelated to influenza in Spain. We carried out a cross-sectional study. Bivariate analysis was performed comparing vaccinated and unvaccinated patients, taking in to account sociodemographic variables and medical risk conditions. Multivariate analysis was performed using multilevel regression models. We included 1038 patients: 602 (58%) had received the influenza vaccine in the 2013-14 season. Three or more general practitioner visits (OR = 1.61; 95% CI 1.19-2.18); influenza vaccination in any of the 3 previous seasons (OR = 13.57; 95% CI 9.45-19.48); and 23-valent pneumococcal polysaccharide vaccination (OR = 1.97; 95% CI 1.38-2.80) were associated with receiving the influenza vaccine. Vaccination coverage of hospitalized elderly people is low in Spain and some predisposing characteristics influence vaccination coverage. Healthcare workers should take these characteristics into account and be encouraged to proactively propose influenza vaccination to all patients aged >= 65 years. PMID- 26824386 TI - Discovery of a Potent Class I Protein Arginine Methyltransferase Fragment Inhibitor. AB - Protein methyltransferases (PMTs) are a promising target class in oncology and other disease areas. They are composed of SET domain methyltransferases and structurally unrelated Rossman-fold enzymes that include protein arginine methyltransferases (PRMTs). In the absence of a well-defined medicinal chemistry tool-kit focused on PMTs, most current inhibitors were identified by screening large and diverse libraries of leadlike molecules. So far, no successful fragment based approach was reported against this target class. Here, by deconstructing potent PRMT inhibitors, we find that chemical moieties occupying the substrate arginine-binding site can act as efficient fragment inhibitors. Screening a fragment library against PRMT6 produced numerous hits, including a 300 nM inhibitor (ligand efficiency of 0.56) that decreased global histone 3 arginine 2 methylation in cells, and can serve as a warhead for the development of PRMT chemical probes. PMID- 26824387 TI - Toxoplasma gondii peptide ligands open the gate of the HLA class I binding groove. AB - HLA class I presentation of pathogen-derived peptide ligands is essential for CD8+ T-cell recognition of Toxoplasma gondii infected cells. Currently, little data exist pertaining to peptides that are presented after T. gondii infection. Herein we purify HLA-A*02:01 complexes from T. gondii infected cells and characterize the peptide ligands using LCMS. We identify 195 T. gondii encoded ligands originating from both secreted and cytoplasmic proteins. Surprisingly, T. gondii ligands are significantly longer than uninfected host ligands, and these longer pathogen-derived peptides maintain a canonical N-terminal binding core yet exhibit a C-terminal extension of 1-30 amino acids. Structural analysis demonstrates that binding of extended peptides opens the HLA class I F' pocket, allowing the C-terminal extension to protrude through one end of the binding groove. In summary, we demonstrate that unrealized structural flexibility makes MHC class I receptive to parasite-derived ligands that exhibit unique C-terminal peptide extensions. PMID- 26824388 TI - Single-cell analysis of transcription kinetics across the cell cycle. AB - Transcription is a highly stochastic process. To infer transcription kinetics for a gene-of-interest, researchers commonly compare the distribution of mRNA copy number to the prediction of a theoretical model. However, the reliability of this procedure is limited because the measured mRNA numbers represent integration over the mRNA lifetime, contribution from multiple gene copies, and mixing of cells from different cell-cycle phases. We address these limitations by simultaneously quantifying nascent and mature mRNA in individual cells, and incorporating cell cycle effects in the analysis of mRNA statistics. We demonstrate our approach on Oct4 and Nanog in mouse embryonic stem cells. Both genes follow similar two-state kinetics. However, Nanog exhibits slower ON/OFF switching, resulting in increased cell-to-cell variability in mRNA levels. Early in the cell cycle, the two copies of each gene exhibit independent activity. After gene replication, the probability of each gene copy to be active diminishes, resulting in dosage compensation. PMID- 26824389 TI - Mutational scanning reveals the determinants of protein insertion and association energetics in the plasma membrane. AB - Insertion of helix-forming segments into the membrane and their association determines the structure, function, and expression levels of all plasma membrane proteins. However, systematic and reliable quantification of membrane-protein energetics has been challenging. We developed a deep mutational scanning method to monitor the effects of hundreds of point mutations on helix insertion and self association within the bacterial inner membrane. The assay quantifies insertion energetics for all natural amino acids at 27 positions across the membrane, revealing that the hydrophobicity of biological membranes is significantly higher than appreciated. We further quantitate the contributions to membrane-protein insertion from positively charged residues at the cytoplasm-membrane interface and reveal large and unanticipated differences among these residues. Finally, we derive comprehensive mutational landscapes in the membrane domains of Glycophorin A and the ErbB2 oncogene, and find that insertion and self-association are strongly coupled in receptor homodimers. PMID- 26824390 TI - The beetle amnion and serosa functionally interact as apposed epithelia. AB - Unlike passive rupture of the human chorioamnion at birth, the insect extraembryonic (EE) tissues - the amnion and serosa - actively rupture and withdraw in late embryogenesis. Withdrawal is essential for development and has been a morphogenetic puzzle. Here, we use new fluorescent transgenic lines in the beetle Tribolium castaneum to show that the EE tissues dynamically form a basal basal epithelial bilayer, contradicting the previous hypothesis of EE intercalation. We find that the EE tissues repeatedly detach and reattach throughout development and have distinct roles. Quantitative live imaging analyses show that the amnion initiates EE rupture in a specialized anterior ventral cap. RNAi phenotypes demonstrate that the serosa contracts autonomously. Thus, apposition in a bilayer enables the amnion as 'initiator' to coordinate with the serosa as 'driver' to achieve withdrawal. This EE strategy may reflect evolutionary changes within the holometabolous insects and serves as a model to study interactions between developing epithelia. PMID- 26824393 TI - Stable isotope and high precision concentration measurements confirm that all humans produce and exhale methane. AB - Mammalian formation of methane (methanogenesis) is widely considered to occur exclusively by anaerobic microbial activity in the gastrointestinal tract. Approximately one third of humans, depending on colonization of the gut by methanogenic archaea, are considered methane producers based on the classification terminology of high and low emitters. In this study laser absorption spectroscopy was used to precisely measure concentrations and stable carbon isotope signatures of exhaled methane in breath samples from 112 volunteers with an age range from 1 to 80 years. Here we provide analytical evidence that volunteers exhaled methane levels were significantly above background (inhaled) air. Furthermore, stable carbon isotope values of the exhaled methane unambiguously confirmed that this gas was produced by all of the human subjects studied. Based on the emission and stable carbon isotope patterns of various age groups we hypothesize that next to microbial sources in the gastrointestinal tracts there might be other, as yet unidentified, processes involved in methane formation supporting the idea that humans might also produce methane endogenously in cells. Finally we suggest that stable isotope measurements of volatile organic compounds such as methane might become a useful tool in future medical research diagnostic programs. PMID- 26824391 TI - A stochastic neuronal model predicts random search behaviors at multiple spatial scales in C. elegans. AB - Random search is a behavioral strategy used by organisms from bacteria to humans to locate food that is randomly distributed and undetectable at a distance. We investigated this behavior in the nematode Caenorhabditis elegans, an organism with a small, well-described nervous system. Here we formulate a mathematical model of random search abstracted from the C. elegans connectome and fit to a large-scale kinematic analysis of C. elegans behavior at submicron resolution. The model predicts behavioral effects of neuronal ablations and genetic perturbations, as well as unexpected aspects of wild type behavior. The predictive success of the model indicates that random search in C. elegans can be understood in terms of a neuronal flip-flop circuit involving reciprocal inhibition between two populations of stochastic neurons. Our findings establish a unified theoretical framework for understanding C. elegans locomotion and a testable neuronal model of random search that can be applied to other organisms. PMID- 26824394 TI - Luminescence Properties of SrZrO3/Tb(3+) Perovskite: Host-Dopant Energy-Transfer Dynamics and Local Structure of Tb(3+). AB - SrZrO3 perovskite (SZP) was synthesized using gel-combustion route and characterized systematically using X-ray diffraction and time-resolved photoluminescence techniques. A detailed analysis of the optical properties of Tb(3+) ions in SrZrO3 was performed to correlate them with the local environment of the lanthanide ions in this perovskite. Photoluminescence (PL) spectroscopy showed that emission spectrum consists of host as well as Tb(3+) emission indicating the absence of complete host-dopant energy transfer. On the basis of emission spectrum and PL decay study it was also observed that Tb(3+) is not homogeneously distributed in SrZrO3 perovskite; rather, it is occupying two different sites. It is corroborated using extended X-ray absorption fine structure studies that Tb(3+) is stabilized on both six-coordinated Zr(4+) and eight-coordinated Sr(2) site. The energies calculated using density functional theory (DFT) indicates that Tb occupation in Sr site is energetically more favorable than Zr site. The analysis of valence charge distribution also substantiated our structural stability analysis of site-selective Tb doping in SrZrO3. Time-resolved emission spectroscopy is employed to elucidate the difference in the spectral feature of Tb(3+) ion at Sr(2+) and Zr(4+) site. DFT calculated density of states analysis showed that energy mismatch of Tb-d states with Zr-d and O-p states of SZP makes the energy transfer from host SZP to Tb(3+) ion difficult. PMID- 26824395 TI - Nanomotors responsive to nerve-agent vapor plumes. AB - Enzyme-powered nanomotors responsive to the presence of nerve agents in the surrounding atmosphere are employed for remote detection of chemical vapor threats. Distinct changes in the propulsion behavior, associated with the partition of the sarin simulant diethyl chlorophosphate (DCP), offer reliable and rapid detection of the nerve-agent vapor threat. PMID- 26824392 TI - Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases. AB - Mutations in Park8, encoding for the multidomain Leucine-rich repeat kinase 2 (LRRK2) protein, comprise the predominant genetic cause of Parkinson's disease (PD). G2019S, the most common amino acid substitution activates the kinase two- to threefold. This has motivated the development of LRRK2 kinase inhibitors; however, poor consensus on physiological LRRK2 substrates has hampered clinical development of such therapeutics. We employ a combination of phosphoproteomics, genetics, and pharmacology to unambiguously identify a subset of Rab GTPases as key LRRK2 substrates. LRRK2 directly phosphorylates these both in vivo and in vitro on an evolutionary conserved residue in the switch II domain. Pathogenic LRRK2 variants mapping to different functional domains increase phosphorylation of Rabs and this strongly decreases their affinity to regulatory proteins including Rab GDP dissociation inhibitors (GDIs). Our findings uncover a key class of bona-fide LRRK2 substrates and a novel regulatory mechanism of Rabs that connects them to PD. PMID- 26824397 TI - Migration of DEHP and DINP into dust from PVC flooring products at different surface temperature. AB - Phthalates are important endocrine disrupting chemicals that have been linked to various adverse human health effects. Phthalates are ubiquitously present in indoor environment and could enter humans. Vinyl or PVC floorings have been recognized as one of important sources of phthalate release to indoor environment including house dust. In the present study, we estimated the migration of di(2 ethylhexyl)phthalate (DEHP) and di-isononyl phthalate (DINP) from the flooring materials into the dust under different heating conditions. For this purpose, a small chamber specifically designed for the present study and a Field and Laboratory Emission Cell (FLEC) were used, and four major types of PVC flooring samples including two UV curing paint coated, an uncoated residential, and a wax coated commercial type were tested. Migration of DEHP was observed for an uncoated residential type and a wax-coated commercial type flooring. After 14 days of incubation, the levels of DEHP in the dust sample was determined at room temperature on average (standard deviation) at 384 +/- 19 and 481 +/- 53 MUg/g, respectively. In contrast, migration of DINP was not observed. The migration of DEHP was strongly influenced by surface characteristics such as UV curing coating. In the residential flooring coated with UV curing paint, migration of DEHP was not observed at room temperature. But under the heated condition, the release of DEHP was observed in the dust in the FLEC. Migration of DEHP from flooring materials increased when the flooring was heated (50 degrees C). In Korea, heated flooring system, or 'ondol', is very common mode of heating in residential setting, therefore the contribution of PVC flooring to the total indoor DEHP exposure among general population is expected to be greater especially during winter season when the floor is heated. PMID- 26824398 TI - HSA IIA subdomain-based developing anticancer metal prodrug: a new and improved approach. PMID- 26824399 TI - Surgical versus non-surgical treatment for lumbar spinal stenosis. AB - BACKGROUND: Lumbar spinal stenosis (LSS) is a debilitating condition associated with degeneration of the spine with aging. OBJECTIVES: To evaluate the effectiveness of different types of surgery compared with different types of non surgical interventions in adults with symptomatic LSS. Primary outcomes included quality of life, disability, function and pain. Also, to consider complication rates and side effects, and to evaluate short-, intermediate- and long-term outcomes (six months, six months to two years, five years or longer). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, five other databases and two trials registries up to February 2015. We also screened reference lists and conference proceedings related to treatment of the spine. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing surgical versus non-operative treatments in participants with lumbar spinal stenosis confirmed by clinical and imaging findings. DATA COLLECTION AND ANALYSIS: For data collection and analysis, we followed methods guidelines of the Cochrane Back and Neck Review Group (Furlan 2009) and those provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). MAIN RESULTS: From the 12,966 citations screened, we assessed 26 full-text articles and included five RCTs (643 participants).Low-quality evidence from the meta-analysis performed on two trials using the Oswestry Disability Index (pain-related disability) to compare direct decompression with or without fusion versus multi-modal non-operative care showed no significant differences at six months (mean difference (MD) -3.66, 95% confidence interval (CI) -10.12 to 2.80) and at one year (MD -6.18, 95% CI -15.03 to 2.66). At 24 months, significant differences favoured decompression (MD -4.43, 95% CI -7.91 to -0.96). Low-quality evidence from one small study revealed no difference in pain outcomes between decompression and usual conservative care (bracing and exercise) at three months (risk ratio (RR) 1.38, 95% CI 0.22 to 8.59), four years (RR 7.50, 95% CI 1.00 to 56.48) and 10 years (RR 4.09, 95% CI 0.95 to 17.58).Low-quality evidence from one small study suggested no differences at six weeks in the Oswestry Disability Index for patients treated with minimally invasive mild decompression versus those treated with epidural steroid injections (MD 5.70, 95% CI 0.57 to 10.83; 38 participants). Zurich Claudication Questionnaire (ZCQ) results were better for epidural injection at six weeks (MD -0.60, 95% CI -0.92 to -0.28), and visual analogue scale (VAS) improvements were better in the mild decompression group (MD 2.40, 95% CI 1.92 to 2.88). At 12 weeks, many cross-overs prevented further analysis.Low-quality evidence from a single study including 191 participants favoured the interspinous spacer versus usual conservative treatment at six weeks, six months and one year for symptom severity and physical function.All remaining studies reported complications associated with surgery and conservative side effects of treatment: Two studies reported no major complications in the surgical group, and the other study reported complications in 10% and 24% of participants, including spinous process fracture, coronary ischaemia, respiratory distress, haematoma, stroke, risk of reoperation and death due to pulmonary oedema. AUTHORS' CONCLUSIONS: We have very little confidence to conclude whether surgical treatment or a conservative approach is better for lumbar spinal stenosis, and we can provide no new recommendations to guide clinical practice. However, it should be noted that the rate of side effects ranged from 10% to 24% in surgical cases, and no side effects were reported for any conservative treatment. No clear benefits were observed with surgery versus non-surgical treatment. These findings suggest that clinicians should be very careful in informing patients about possible treatment options, especially given that conservative treatment options have resulted in no reported side effects. High-quality research is needed to compare surgical versus conservative care for individuals with lumbar spinal stenosis. PMID- 26824400 TI - [Comment on the TIDier Checklist]. AB - This comment focuses on the need for and possible impact of the TIDieR reporting guideline. PMID- 26824401 TI - [Better Reporting of Interventions: Template for Intervention Description and Replication (TIDieR) Checklist and Guide]. AB - Without a complete published description of interventions, clinicians and patients cannot reliably implement interventions that are shown to be useful, and other researchers cannot replicate or build on research findings. The quality of description of interventions in publications, however, is remarkably poor. To improve the completeness of reporting, and ultimately the replicability, of interventions, an international group of experts and stakeholders developed the Template for Intervention Description and Replication (TIDieR) checklist and guide. The process involved a literature review for relevant checklists and research, a Delphi survey of an international panel of experts to guide item selection, and a face-to-face panel meeting. The resultant 12-item TIDieR checklist (brief name, why, what (materials), what (procedure), who intervened, how, where, when and how much, tailoring, modifications, how well (planned), how well (actually carried out)) is an extension of the CONSORT 2010 statement (item 5) and the SPIRIT 2013 statement (item 11). While the emphasis of the checklist is on trials, the guidance is intended to apply across all evaluative study designs. This paper presents the TIDieR checklist and guide, with a detailed explanation of each item, and examples of good reporting. The TIDieR checklist and guide should improve the reporting of interventions and make it easier for authors to structure the accounts of their interventions, reviewers and editors to assess the descriptions, and readers to use the information. PMID- 26824402 TI - B-Cell-Deficient and CD8 T-Cell-Depleted Gnotobiotic Pigs for the Study of Human Rotavirus Vaccine-Induced Protective Immune Responses. AB - Genetically modified pigs have become available recently. In this study, we established the gnotobiotic pig model of human rotavirus (HRV) infection using cloned pigs with homozygous disruption in the gene encoding immunoglobulin heavy chain (HCKO), which totally impairs B-cell development. To clarify importance of B cells and cytotoxic T cells in rotavirus immunity, CD8 cells in a subset of the pigs were depleted by injecting antipig CD8 antibodies and the immune phenotypes of all pigs were examined. HCKO pigs, CD8 cell-depleted HCKO pigs, and wild-type (WT) pigs were vaccinated with an attenuated HRV vaccine and challenged with virulent HRV. Protection against HRV infection and diarrhea was assessed postchallenge and detailed T-cell subset responses were determined pre- and postchallenge. Significantly longer duration of virus shedding was seen in vaccinated HCKO pigs than in WT pigs, indicating the importance of B cells in vaccine-induced protective immunity. Vaccinated HCKO/CD8(-) pigs shed significantly higher number of infectious virus than WT pigs and non-CD8-depleted HCKO pigs, indicating the importance of CD8 T cells in controlling virus replication. Therefore, both B cells and CD8 T cells play an important role in the protection against rotavirus infection. HCKO and HCKO/CD8(-) pigs did not differ significantly in diarrhea and virus shedding postchallenge; increased CD4 and CD8(-) gammadelta T-cell responses probably compensated partially for the lack of CD8 T cells. This study demonstrated that HCKO pigs can serve as a valuable model for dissection of protective immune responses against viral infections and diseases. PMID- 26824404 TI - Neck Circumference Is Independently Associated with Cardiometabolic Risk Factors: Cross-Sectional Analysis from ELSA-Brasil. AB - BACKGROUND: Neck circumference (NC) is a simple anthropometric measurement that may be linked with cardiometabolic risk factors. We analyzed the association between NC and a range of cardiometabolic risk factors. METHODS: In a cross sectional and sex-specific analysis of the ELSA-Brasil study (15,105 civil servants aged 35-74 years), we excluded participants with diabetes, taking antihypertensive and/or lipid-lowering drugs. Cardiometabolic risk factors were homeostasis model assessment of insulin resistance (>= 75th percentile), low high density lipoprotein (HDL; <50 mg/dL for women and <40 mg/dL for men), high triglycerides >= 150 mg/dL, systolic blood pressure >= 130 mmHg, or diastolic blood pressure >= 85 mmHg. Logistic regression models were built to analyze the association between individual and clustered risk factors and 1-standard deviation (SD) increase in NC after adjustments for age, smoking, alcohol, body mass index, and waist circumference. RESULTS: We analyzed 8726 participants (56.3% women), with a mean age of 49.2 +/- 8.0 years. Mean NC was 38.9 +/- 2.6 cm for men and 33.4 +/- 2.6 cm for women. Fully adjusted odds ratios (ORs) [95% confidence intervals (CIs)] per 1-SD increase in NC in men and women were, respectively, 1.32 (1.16-1.51) and 1.47 (1.31-1.64) for insulin resistance; 1.24 (1.11-1.39) and 1.25 (1.11-1.40) for raised blood pressure; 1.50 (1.33-1.70) and 1.51 (1.33-1.70) for high triglycerides; and 1.22 (0.92-1.61) and 1.54 (1.23 1.86) for low HDL. Fully adjusted ORs (95% CI) of three or more clustered risk factors per 1-SD increase in NC in men and women were 1.54 (1.34-1.79) and 1.71 (1.41-2.06). CONCLUSION: NC is significantly and independently associated with cardiometabolic risk factors in a well-defined apparently healthy population. PMID- 26824405 TI - En bloc temporal bone resections in squamous cell carcinoma of the ear. Technique, principles, and limits. AB - CONCLUSIONS: En bloc resection should always be primarily considered in ear carcinoma, also in advanced tumors growing beyond the walls of the external auditory canal, because it achieves a full specimen for histopathological evaluation and allows a correlation between clinical, pathological features, and outcomes. OBJECTIVE AND METHODS: Dismal outcome of surgical and radiotherapic therapies for advanced ear carcinoma required a critical discussion of the oncological principles of treatment. Our analysis involved preliminarily a detailed description of surgical technique including the contribution of modern skull base microsurgery. RESULTS: Evident limits in diagnostic protocols, surgical treatment and outcome evaluation modalities pointed to the need of a new approach towards an accurate definition of pre-operative tumor location, size, and behavior. En bloc resection achieved a specimen for a final pathological evaluation and an adjunctive piecemeal excision was necessary only whenever resection was not felt falling in safe, tumor-free tissue. Chemotherapy and radiotherapy should be considered in selected cases for adjuvant treatment. PMID- 26824403 TI - Hippocampus and amygdala volumes from magnetic resonance images in children: Assessing accuracy of FreeSurfer and FSL against manual segmentation. AB - The volumetric quantification of brain structures is of great interest in pediatric populations because it allows the investigation of different factors influencing neurodevelopment. FreeSurfer and FSL both provide frequently used packages for automatic segmentation of brain structures. In this study, we examined the accuracy and consistency of those two automated protocols relative to manual segmentation, commonly considered as the "gold standard" technique, for estimating hippocampus and amygdala volumes in a sample of preadolescent children aged between 6 to 11 years. The volumes obtained with FreeSurfer and FSL-FIRST were evaluated and compared with manual segmentations with respect to volume difference, spatial agreement and between- and within-method correlations. Results highlighted a tendency for both automated techniques to overestimate hippocampus and amygdala volumes, in comparison to manual segmentation. This was more pronounced when using FreeSurfer than FSL-FIRST and, for both techniques, the overestimation was more marked for the amygdala than the hippocampus. Pearson correlations support moderate associations between manual tracing and FreeSurfer for hippocampus (right r=0.69, p<0.001; left r=0.77, p<0.001) and amygdala (right r=0.61, p<0.001; left r=0.67, p<0.001) volumes. Correlation coefficients between manual segmentation and FSL-FIRST were statistically significant (right hippocampus r=0.59, p<0.001; left hippocampus r=0.51, p<0.001; right amygdala r=0.35, p<0.001; left amygdala r=0.31, p<0.001) but were significantly weaker, for all investigated structures. When computing intraclass correlation coefficients between manual tracing and automatic segmentation, all comparisons, except for left hippocampus volume estimated with FreeSurfer, failed to reach 0.70. When looking at each method separately, correlations between left and right hemispheric volumes showed strong associations between bilateral hippocampus and bilateral amygdala volumes when assessed using manual segmentation or FreeSurfer. These correlations were significantly weaker when volumes were assessed with FSL FIRST. Finally, Bland-Altman plots suggest that the difference between manual and automatic segmentation might be influenced by the volume of the structure, because smaller volumes were associated with larger volume differences between techniques. These results demonstrate that, at least in a pediatric population, the agreement between amygdala and hippocampus volumes obtained with automated FSL-FIRST and FreeSurfer protocols and those obtained with manual segmentation is not strong. Visual inspection by an informed individual and, if necessary, manual correction of automated segmentation outputs are important to ensure validity of volumetric results and interpretation of related findings. PMID- 26824406 TI - Tracking Sodium-Antimonide Phase Transformations in Sodium-Ion Anodes: Insights from Operando Pair Distribution Function Analysis and Solid-State NMR Spectroscopy. AB - Operando pair distribution function (PDF) analysis and ex situ (23)Na magic-angle spinning solid-state nuclear magnetic resonance (MAS ssNMR) spectroscopy are used to gain insight into the alloying mechanism of high-capacity antimony anodes for sodium-ion batteries. Subtraction of the PDF of crystalline NaxSb phases from the total PDF, an approach constrained by chemical phase information gained from (23)Na ssNMR in reference to relevant model compounds, identifies two previously uncharacterized intermediate species formed electrochemically; a-Na(3-x)Sb (x ~ 0.4-0.5), a structure locally similar to crystalline Na3Sb (c-Na3Sb) but with significant numbers of sodium vacancies and a limited correlation length, and a Na(1.7)Sb, a highly amorphous structure featuring some Sb-Sb bonding. The first sodiation breaks down the crystalline antimony to form first a-Na(3-x)Sb and, finally, crystalline Na3Sb. Desodiation results in the formation of an electrode formed of a composite of crystalline and amorphous antimony networks. We link the different reactivity of these networks to a series of sequential sodiation reactions manifesting as a cascade of processes observed in the electrochemical profile of subsequent cycles. The amorphous network reacts at higher voltages reforming a-Na(1.7)Sb, then a-Na(3-x)Sb, whereas lower potentials are required for the sodiation of crystalline antimony, which reacts to form a-Na(3-x)Sb without the formation of a-Na(1.7)Sb. a-Na(3-x)Sb is converted to crystalline Na3Sb at the end of the second discharge. We find no evidence of formation of NaSb. Variable temperature (23)Na NMR experiments reveal significant sodium mobility within c-Na3Sb; this is a possible contributing factor to the excellent rate performance of Sb anodes. PMID- 26824407 TI - Methane Emissions from Conventional and Unconventional Natural Gas Production Sites in the Marcellus Shale Basin. AB - There is a need for continued assessment of methane (CH4) emissions associated with natural gas (NG) production, especially as recent advancements in horizontal drilling combined with staged hydraulic fracturing technologies have dramatically increased NG production (we refer to these wells as "unconventional" NG wells). In this study, we measured facility-level CH4 emissions rates from the NG production sector in the Marcellus region, and compared CH4 emissions between unconventional NG (UNG) well pad sites and the relatively smaller and older "conventional" NG (CvNG) sites that consist of wells drilled vertically into permeable geologic formations. A top-down tracer-flux CH4 measurement approach utilizing mobile downwind intercepts of CH4, ethane, and tracer (nitrous oxide and acetylene) plumes was performed at 18 CvNG sites (19 individual wells) and 17 UNG sites (88 individual wells). The 17 UNG sites included four sites undergoing completion flowback (FB). The mean facility-level CH4 emission rate among UNG well pad sites in routine production (18.8 kg/h (95% confidence interval (CI) on the mean of 12.0-26.8 kg/h)) was 23 times greater than the mean CH4 emissions from CvNG sites. These differences were attributed, in part, to the large size (based on number of wells and ancillary NG production equipment) and the significantly higher production rate of UNG sites. However, CvNG sites generally had much higher production-normalized CH4 emission rates (median: 11%; range: 0.35-91%) compared to UNG sites (median: 0.13%, range: 0.01-1.2%), likely resulting from a greater prevalence of avoidable process operating conditions (e.g., unresolved equipment maintenance issues). At the regional scale, we estimate that total annual CH4 emissions from 88 500 combined CvNG well pads in Pennsylvania and West Virginia (660 Gg (95% CI: 500 to 800 Gg)) exceeded that from 3390 UNG well pads by 170 Gg, reflecting the large number of CvNG wells and the comparably large fraction of CH4 lost per unit production. The new emissions data suggest that the recently instituted Pennsylvania CH4 emissions inventory substantially underestimates measured facility-level CH4 emissions by >10-40 times for five UNG sites in this study. PMID- 26824409 TI - Commentary on 'A one-year practice-based learning programme for new general practice nurses in Scotland: evaluation of the pilot'. PMID- 26824408 TI - The Effect of Limiting the Range of Perimetric Sensitivities on Pointwise Assessment of Visual Field Progression in Glaucoma. AB - PURPOSE: Automated perimetry does not produce reliable estimates of true psychophysical threshold in glaucomatous visual fields when the perimetric threshold falls below 15 to 19 dB. It may be possible to truncate testing at such locations and not use stimuli with very high contrast. However, this can only be recommended if it does not harm the ability to monitor change. This study examined the effect of applying such a cutoff by censoring sensitivities in two existing longitudinal datasets. METHODS: Series of six visual fields were taken from participants with glaucoma or high-risk ocular hypertension in the Portland Progression Project (P3) and Rotterdam Eye Study (RES). Pointwise linear regression was used to find "progressing" locations, defined as a slope <= -1 dB/y with P < 1%. An eye was labeled progressing if >=3 locations were progressing. This was repeated after setting any sensitivities below the cutoff value C (CdB) to instead equal that value for different integer values of CdB. RESULTS: In the P3 cohort tested using Swedish Interactive Testing Algorithm (SITA) Standard, censoring below 15 to 19 dB did not reduce the number of eyes flagged as progressing. For the RES cohort tested using the Full Threshold algorithm, censoring below 10 dB did not reduce the number of eyes flagged as progressing, but a modest reduction was seen for CdB between 10 dB and 15 to 19 dB. CONCLUSIONS: The proportion of eyes flagged as progressing was not decreased by censoring unreliable sensitivities. Restricting the range of contrast used in clinical perimetry may be possible without hampering the ability to monitor glaucomatous visual field progression. PMID- 26824410 TI - Genome-scale estimate of the metabolic turnover of E. coli from the energy balance analysis. AB - In this article the notion of metabolic turnover is revisited in the light of recent results of out-of-equilibrium thermodynamics. By means of Monte Carlo methods we perform an exact sampling of the enzymatic fluxes in a genome scale metabolic network of E. coli in stationary growth conditions from which we infer the metabolites turnover times. However the latter are inferred from net fluxes, and we argue that this approximation is not valid for enzymes working nearby thermodynamic equilibrium. We recalculate turnover times from total fluxes by performing an energy balance analysis of the network and recurring to the fluctuation theorem. We find in many cases values one of order of magnitude lower, implying a faster picture of intermediate metabolism. PMID- 26824411 TI - Intranasal Vaccination against HIV-1 with Adenoviral Vector-Based Nanocomplex Using Synthetic TLR-4 Agonist Peptide as Adjuvant. AB - Recombinant type 5 adenovirus (rAd5) vaccines hold the promise to prevent HIV-1 infections. Intranasal vaccination not only stimulates systemic immunity but also elicits mucosal immunity that provides first defense for mucosally transmitted diseases like HIV-1. Adjuvants such as TLR agonists are usually codelivered with antigens to enhance the immunogenicity of vaccines. Here, we present a rAd5 vaccine delivery system using DEG-PEI as the carrier. Adenovirus encoding HIV gag was used as antigen, and was complexed with DEG-PEI polymer via electrostatic interaction. A novel synthetic TLR-4 agonist, RS09, was either chemically linked with DEG-PEI (DP-RS09) or physically mixed with it(DP/RS09) to enhance the immunogenticity of rAd5 vaccine. After intranasal immunization, the systemic antigen-specific immune responses and cytotoxicity T lymphocytes responses induced by DP-RS09-rAd5 and DP/RS09-rAd5 were analyzed. The mucosal secretory IgA level was detected in both nasal and vaginal washes to determine the mucosal immunity. Furthermore, cytokine productions on RAW264.7 cells were tested after preincubation with TLR-4 pathway inhibitors. The results indicated that DEG-PEI could facilitate the intranasal delivery of rAd5 vaccine. Both chemically linked (DP-RS09) and physically mixed RS09 (DP/RS09) could further enhance the mucosal immunity of rAd5 vaccine via TLR-4 pathway. This RS09 adjuvanted DEG-PEI polymer represents a potential intranasal vaccine delivery system and may have a wider application for other viral vectors. PMID- 26824412 TI - 64Cu-Doped PdCu@Au Tripods: A Multifunctional Nanomaterial for Positron Emission Tomography and Image-Guided Photothermal Cancer Treatment. AB - This article reports a facile synthesis of radiolabeled PdCu@Au core-shell tripods for use in positron emission tomography (PET) and image-guided photothermal cancer treatment by directly incorporating radioactive (64)Cu atoms into the crystal lattice. The tripod had a unique morphology determined by the PdCu tripod that served as a template for the coating of Au shell, in addition to well-controlled specific activity and physical dimensions. The Au shell provided the nanostructure with strong absorption in the near-infrared region and effectively prevented the Cu and (64)Cu atoms in the core from oxidization and dissolution. When conjugated with D-Ala1-peptide T-amide (DAPTA), the core-shell tripods showed great enhancement in targeting the C-C chemokine receptor 5 (CCR5), a newly identified theranostic target up-regulated in triple negative breast cancer (TNBC). Specifically, the CCR5-targeted tripods with an arm length of about 45 nm showed 2- and 6-fold increase in tumor-to-blood and tumor-to muscle uptake ratios, respectively, relative to their nontargeted counterpart in an orthotopic mouse 4T1 TNBC model at 24 h postinjection. The targeting specificity was further validated via a competitive receptor blocking study. We also demonstrated the use of these targeted, radioactive tripods for effective photothermal treatment in the 4T1 tumor model as guided by PET imaging. The efficacy of treatment was confirmed by the significant reduction in tumor metabolic activity revealed through the use of (18)F-fluorodeoxyglucose PET/CT imaging. Taken together, we believe that the (64)Cu-doped PdCu@Au tripods could serve as a multifunctional platform for both PET imaging and image-guided photothermal cancer therapy. PMID- 26824414 TI - Statistical Correlations between NMR Spectroscopy and Direct Infusion FT-ICR Mass Spectrometry Aid Annotation of Unknowns in Metabolomics. AB - NMR spectroscopy and mass spectrometry are the two major analytical platforms for metabolomics, and both generate substantial data with hundreds to thousands of observed peaks for a single sample. Many of these are unknown, and peak assignment is generally complex and time-consuming. Statistical correlations between data types have proven useful in expediting this process, for example, in prioritizing candidate assignments. However, this approach has not been formally assessed for the comparison of direct-infusion mass spectrometry (DIMS) and NMR data. Here, we present a systematic analysis of a sample set (tissue extracts), and the utility of a simple correlation threshold to aid metabolite identification. The correlations were surprisingly successful in linking structurally related signals, with 15 of 26 NMR-detectable metabolites having their highest correlation to a cognate MS ion. However, we found that the distribution of the correlations was highly dependent on the nature of the MS ion, such as the adduct type. This approach should help to alleviate this important bottleneck where both 1D NMR and DIMS data sets have been collected. PMID- 26824413 TI - Patient-reported problematic symptoms in an ALS treatment trial. AB - This study was undertaken to determine which symptoms are perceived to be most problematic for patients with ALS and how their severity changes over time. A retrospective study was performed of data from a randomized, double-blind, placebo-controlled trial of ceftriaxone in ALS. Participants completed the ALS Specific Quality of Life Instrument (ALSSQoL) at baseline and at intervals up to 96 weeks. Ten ALSSQoL items ask participants to rate how problematic symptoms are (the subjective feeling of burden of these symptoms), ranging from 0 (no problem) to 10 (tremendous problem). Six are non-bulbar (pain, fatigue, breathing, strength and ability to move, sleep, and bowel and bladder) and four are bulbar (eating, speaking, excessive saliva, and mucus). Results revealed that there were 82 subjects (56% males, mean age 53 +/- 10.3 years) with ALSSQoL data for weeks 0 and 96. All 10 symptoms became more problematic over time. For non-bulbar symptoms, strength/ability to move and fatigue were the most problematic. Speaking was the most problematic bulbar symptom. In conclusion, although all the symptoms in the ALSSQoL were acknowledged as problematic, some had greater impact than others. All became more problematic over time. This should help prioritize research into symptom management, and assist individual clinicians in their approach to patient care. PMID- 26824415 TI - Mechanism of progestin resistance in endometrial precancer/cancer through Nrf2 AKR1C1 pathway. AB - Progestin resistance is a main obstacle for endometrial precancer/cancer conservative therapy. Therefore, biomarkers to predict progestin resistance and studies to gain a more detailed understanding of the mechanism are needed. The antioxidant Nrf2-AKR1C1 signal pathway exerts chemopreventive activity. However whether it plays a role in progestin resistance has not been explored. In this study, elevated levels of AKR1C1 and Nrf2 were found in progestin-resistant endometrial epithelia, but not in responsive endometrial glands. Exogenous overexpression of Nrf2/AKR1C1 resulted in progestin resistance. Inversely, silencing of Nrf2 or AKR1C1 rendered endometrial cancer cells more susceptible to progestin treatment. Moreover, medroxyprogesterone acetate withdrawal resulted in suppression of Nrf2/AKR1C1 expression accompanied by a reduction of cellular proliferative activity. In addition, brusatol and metformin overcame progestin resistance by down-regulating Nrf2/AKR1C1 expression. Our findings suggest that overexpression of Nrf2 and AKR1C1 in endometrial precancer/cancer may be part of the molecular mechanisms underlying progestin resistance. If validated in a larger cohort, overexpression of Nrf2 and AKR1C1 may prove to be useful biomarkers to predict progestin resistance. Targeting the Nrf2/AKR1C1 pathway may represent a new therapeutic strategy for treatment of endometrial hyperplasia/cancer. PMID- 26824417 TI - IL-32theta inhibits stemness and epithelial-mesenchymal transition of cancer stem cells via the STAT3 pathway in colon cancer. AB - Interleukin (IL)-32 is a well-known cytokine associated with inflammation, virus infections and cancer. IL-32theta is a newly identified isoform of IL-32, whose function has yet to be elucidated. In this study, we investigated IL-32theta function in colon cancer stem cells. Using samples from colon cancer patients, we found that the expression of IL-32theta mRNAs was significantly suppressed in tumor regions. We investigated the effects of IL-32theta on colon cancer. Ectopic expression of IL-32theta attenuated invasion, migration in vitro and in vivo tumorigenicity of colon cancer cells. IL-32theta inhibited epithelial-mesenchymal transition (EMT), resulting in the suppression of their migratory and invasive capabilities of HT29 colon cancer cells. In addition, IL-32theta altered various properties of CSCs, including sphere formation and expression of stemness related genes. IL-32theta directly bound to STAT3 and inhibited its nuclear translocation, leading to inhibited transcription of downstream factors, including Bmi1 and ZEB1. We showed that IL-32theta inhibited the STAT3-ZEB1 pathway and consequently inhibited key factors of stemness and EMT. Taken together, our findings reveal that IL-32theta can be a tumor suppressor, indicating that IL-32theta could possibly be used in therapies for colon cancer. PMID- 26824416 TI - Resistance to the nucleotide analogue cidofovir in HPV(+) cells: a multifactorial process involving UMP/CMP kinase 1. AB - Human papillomavirus (HPV) is responsible for cervical cancer, and its role in head and neck carcinoma has been reported. No drug is approved for the treatment of HPV-related diseases but cidofovir (CDV) exhibits selective antiproliferative activity. In this study, we analyzed the effects of CDV-resistance (CDVR) in two HPV(+) (SiHaCDV and HeLaCDV) and one HPV(-) (HaCaTCDV) tumor cell lines. Quantification of CDV metabolites and analysis of the sensitivity profile to chemotherapeutics was performed. Transporters expression related to multidrug resistance (MRP2, P-gp, BCRP) was also investigated. Alterations of CDV metabolism in SiHaCDV and HeLaCDV, but not in HaCaTCDV, emerged via impairment of UMP/CMPK1 activity. Mutations (P64T and R134M) as well as down-regulation of UMP/CMPK1 expression were observed in SiHaCDV and HeLaCDV, respectively. Altered transporters expression in SiHaCDV and/or HeLaCDV, but not in HaCaTCDV, was also noted. Taken together, these results indicate that CDVR in HPV(+) tumor cells is a multifactorial process. PMID- 26824418 TI - Meta-analysis of the differentially expressed microRNA profiles in nasopharyngeal carcinoma. AB - MicroRNAs(miRNAs), as non-coding molecules, were proved to be correlated with gene expression in naspharyngeal carcinoma (NPC) development. In this research, a comprehensive meta-analysis of eight independent miRNA expression studies in NPC was preformed by using robust rank aggregation method (RRA), which contained a total of 775 tumor and 227 non-cancerous samples. There were 7 significant dysregulated miRNAs identified including three increased (miR-483-5p, miR-29c-3p and miR-205-5p) and four decreased (miR-29b-3p, let-7d-5p, miR-100- 5p and let-7g 5p) miRNAs. Subsequently, the miRNA target prediction and pathway enrichment analysis were carried out to find out the biological and functional relevant genes involved in the meta-signature miRNA regulation. Finally, several signaling and cancer pathogenesis pathways were suggested to be more frequently associated with the progression of NPC. In this research the meta-signature miRNA identified may be used to develop a series of diagnostic and prognostic biomarkers for NPC that serve specificity for use in clinics. PMID- 26824419 TI - WISP-1 promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-300 in human oral squamous cell carcinoma cells. AB - Oral squamous cell carcinoma (OSCC), which accounts for nearly 90% of head and neck cancers, is characterized by a poor prognosis and a low survival rate. Vascular endothelial growth factor-C (VEGF-C) has been implicated in lymphangiogenesis and is correlated with cancer metastasis. WNT1-inducible signaling pathway protein-1 (WISP)-1/CCN4 is an extracellular matrix-related protein that belongs to the CCN family and stimulates many biological functions. Our previous studies showed that WISP-1 plays an important role in OSCC migration and angiogenesis. However, the effect of WISP-1 on VEGF-C regulation and lymphangiogenesis in OSCC is poorly understood. Here, we showed a correlation between WISP-1 and VEGF-C in tissue specimens from patients with OSCC. To examine the lymphangiogenic effect of WISP-1, we used human lymphatic endothelial cells (LECs) to mimic lymphatic vessel formation. The results showed that conditioned media from WISP-1-treated OSCC cells promoted tube formation and cell migration in LECs. We also found that WISP-1-induced VEGF-C is mediated via the integrin alphavbeta3/integrin-linked kinase (ILK)/Akt signaling pathway. In addition, the expression of microRNA-300 (miR-300) was inhibited by WISP-1 via the integrin alphavbeta3/ILK/Akt cascade. Collectively, these results reveal the detailed mechanism by which WISP-1 promotes lymphangiogenesis via upregulation of VEGF-C expression in OSCC. Therefore, WISP-1 could serve as therapeutic target to prevent metastasis and lymphangiogenesis in OSCC. PMID- 26824420 TI - ACTP: A webserver for predicting potential targets and relevant pathways of autophagy-modulating compounds. AB - Autophagy (macroautophagy) is well known as an evolutionarily conserved lysosomal degradation process for long-lived proteins and damaged organelles. Recently, accumulating evidence has revealed a series of small-molecule compounds that may activate or inhibit autophagy for therapeutic potential on human diseases. However, targeting autophagy for drug discovery still remains in its infancy. In this study, we developed a webserver called Autophagic Compound-Target Prediction (ACTP) (http://actp.liu-lab.com/) that could predict autophagic targets and relevant pathways for a given compound. The flexible docking of submitted small molecule compound (s) to potential autophagic targets could be performed by backend reverse docking. The webpage would return structure-based scores and relevant pathways for each predicted target. Thus, these results provide a basis for the rapid prediction of potential targets/pathways of possible autophagy activating or autophagy-inhibiting compounds without labor-intensive experiments. Moreover, ACTP will be helpful to shed light on identifying more novel autophagy activating or autophagy-inhibiting compounds for future therapeutic implications. PMID- 26824421 TI - Osteopontin promotes epithelial-mesenchymal transition of hepatocellular carcinoma through regulating vimentin. AB - Our previous studies have found that osteopontin (OPN) is a promoter for hepatocellular carcinoma (HCC) progression. However, the molecular mechanism by which OPN enhances HCC metastasis remains elusive. Epithelial-mesenchymal transition (EMT) of cancer cells plays a pivotal role in promoting metastatic process. In this study, we demonstrated that OPN promotes HCC metastasis by inducing an EMT-like, more aggressive cellular phenotype in vitro and in vivo. Furthermore, OPN was identified to interact with vimentin by reciprocal OPN and vimentin immunoprecipitation as well as co-immunofluorescence examination. By using deletion mutants, we found that the residues between 246 and 406 in vimentin are required for binding to OPN. Importantly, OPN significantly increased vimentin stability through inhibition of its protein degradation. Knockdown of vimentin neutralized the EMT induced by OPN both in vitro and in vivo. Moreover, a significant correlation between OPN and vimentin levels was found in clinical HCC specimens and their combination had a worse prognosis with shorter overall survival (OS) and time to recurrence (TTR). In multivariate analysis, OPN and their combination were demonstrated to be independent prognostic indicators for OS and TTR of HCC patients. Collectively, this study indicates that OPN can induce EMT of HCC cells through increasing vimentin stability, which provides more in-depth understanding about the molecular mechanisms of OPN in promoting HCC metastasis and opens tantalizing therapeutic possibilities in HCC. PMID- 26824422 TI - Cyclic AMP responsive element-binding protein promotes renal cell carcinoma proliferation probably via the expression of spindle and kinetochore-associated protein 2. AB - Emerging evidence shows that the aberrantly expressed cyclic AMP responsive element-binding protein (CREB) is associated with tumor development and progression in several cancers. Spindle and kinetochore-associated protein 2 (SKA2) is essential for regulating the progress of mitosis. In this study, we evaluate in vitro and in vivo the functional relationship between CREB and SKA2 in renal cell carcinoma (RCC). Suppressing and replenishing CREB levels were used to manipulate SKA2 expression, observing the effects on RCC cell lines. Computational prediction and ChIP assay identified that CREB targeted ska2 by binding its CRE sequence in the human genome. Overexpression of CREB reversed the inhibited cell growth following siSKA2 treatment, and reduced the number of cells holding in mitosis. Decreased expression of CREB suppressed RCC cell growth and xenograft tumor formation, accompanied by reduced expression of SKA2. In RCC tumor samples from patients, mRNA for SKA2 were plotted near those of CREB in each sample, with significantly increased immunohistochemical staining of higher SKA2 and CREB in the higher TNM stages. The study adds evidence that CREB, a tumor oncogene, promotes RCC proliferation. It probably achieves this by increasing SKA2 expression. PMID- 26824424 TI - Esophageal stents: when and how. AB - Esophageal stents are devices used to alleviate dysphagia and treat leaks and perforations. Successful esophageal stenting requires definition of the abnormal anatomy such as stricture length or location of the leak, proper stent selection and deployment. This requires detailed knowledge of characteristics of the currently available stents. Self-expanding metal stents whether fully or partially covered have become the mainstay of treatment of esophageal cancer related dysphagia as they provide quick relief of symptoms and have a favorable safety and efficacy profile, compared to other modalities such as radiation, laser, and argon plasma coagulation. They are also the initial treatment of choice for both malignant and benign fistulae. Stents are also used in benign refractory strictures but long-term stricture resolution rates are low in this setting. Fully covered metal stents are relatively easier to remove compared to partially covered stents; optimal time interval for removal depends on the indication for stenting and the clinical status of the patient. Stent related adverse events include chest pain, reflux, migration, and recurrent obstruction. Serious adverse events occur in less than 5% with procedure-related mortality of less than 2%. Techniques such as placement of hemostatic clips, Over The Scope clips, and endoscopic suturing are being used to decrease the migration risk but the optimal approach has not been defined. Antireflux measures are needed when a stent is placed across the gastroesophageal junction. Stents with antireflux designs do not appear to offer additional benefit compared to the conventional stent designs. Newer stent designs including biodegradable, drug eluting and radioactive stents are currently being investigated. PMID- 26824423 TI - Heterogenous ribonucleoprotein A18 (hnRNP A18) promotes tumor growth by increasing protein translation of selected transcripts in cancer cells. AB - The heterogenous ribonucleoprotein A18 (hnRNP A18) promotes tumor growth by coordinating the translation of selected transcripts associated with proliferation and survival. hnRNP A18 binds to and stabilizes the transcripts of pro-survival genes harboring its RNA signature motif in their 3'UTRs. hnRNP A18 binds to ATR, RPA, TRX, HIF-1alpha and several protein translation factor mRNAs on polysomes and increases de novo protein translation under cellular stress. Most importantly, down regulation of hnRNP A18 decreases proliferation, invasion and migration in addition to significantly reducing tumor growth in two mouse xenograft models, melanoma and breast cancer. Moreover, tissue microarrays performed on human melanoma, prostate, breast and colon cancer indicate that hnRNP A18 is over expressed in 40 to 60% of these malignant tissue as compared to normal adjacent tissue. Immunohistochemistry data indicate that hnRNP A18 is over expressed in the stroma and hypoxic areas of human tumors. These data thus indicate that hnRNP A18 can promote tumor growth in in vivo models by coordinating the translation of pro-survival transcripts to support the demands of proliferating cells and increase survival under cellular stress. hnRNP A18 therefore represents a new target to selectively inhibit protein translation in tumor cells. PMID- 26824425 TI - Pre-Exposure Prophylaxis (PrEP) for Safer Conception Among Serodifferent Couples: Findings from Healthcare Providers Serving Patients with HIV in Seven US Cities. AB - Pre-exposure prophylaxis (PrEP) can reduce the risk of HIV transmission among serodifferent couples trying to conceive, yet provider knowledge, attitudes, and experience utilizing PrEP for this purpose are largely unexamined. Trained interviewers conducted phone interviews with healthcare providers treating patients with HIV in seven cities (Atlanta, Baltimore, Houston, Kansas City, Newark, Philadelphia, and San Francisco, N = 85 total). Quantitative and qualitative data were analyzed to describe experience, concerns, and perceived barriers to prescribing PrEP for safer conception. Providers (67.1% female, 43 mean years of age, 70.4% white, 10 mean years treating HIV+ patients, 56% in academic vs. community facilities, 62.2% MD) discussed both benefits and concerns of PrEP for safer conception among serodifferent couples. Only 18.8% of providers reported experience prescribing PrEP, 74.2% were willing to prescribe it under ideal circumstances, and 7.0% were not comfortable prescribing PrEP. Benefits included added protection and a greater sense of control for the HIV-negative partner. Concerns were categorized as clinical, system-level, cost, or behavioral. Significant differences in provider characteristics existed across sites, but experience with PrEP for safer conception did not, p = 0.14. Despite limited experience, most providers were open to recommending PrEP for safer conception as long as patients understood the range of concerns and could make informed decisions. Strategies to identify and link serodifferent couples to PrEP services and clinical guidance specific to PrEP for safer conception are needed. PMID- 26824426 TI - Steered molecular dynamics study of inhibitor binding in the internal binding site in dehaloperoxidase-hemoglobin. AB - The binding free energy of 4-bromophenol (4-BP), an inhibitor that binds in the internal binding site in dehaloperoxidase-hemoglobin (DHP) was calculated using Molecular Dynamics (MD) methods combined with pulling or umbrella sampling. The effects of systematic changes in the pulling speed, pulling force constant and restraint force constant on the calculated potential of mean force (PMF) are presented in this study. The PMFs calculated using steered molecular dynamics (SMD) were validated by umbrella sampling (US) in the strongly restrained regime. A series of restraint force constants ranging from 1000 down to 5 kJ/(mol nm(2)) were used in SMD simulations. This range was validated using US, however noting that weaker restraints give rise to a broader sampling of configurations. This comparison was further tested by a pulling simulation conducted without any restraints, which was observed to have a value closest to the experimentally measured free energy for binding of 4-BP to DHP based on ultraviolet-visible (UV vis) and resonance Raman spectroscopies. The protein-inhibitor system is well suited for fundamental study of free energy calculations because the DHP protein is relatively small and the inhibitor is quite rigid. Simulation configuration structures are compared to the X-ray crystallography structures of the binding site of 4-BP in the distal pocket above the heme. PMID- 26824427 TI - Xanthan Exopolysaccharide: Cu(2+) Complexes Affected from the pH-Dependent Conformational State; Implications for Environmentally Relevant Biopolymers. AB - The conformational impact of environmental biopolymers on metal sorption was studied through Cu sorption on xanthan. The apparent Cu(2+) complexation constant (logK; Cu(2+) + L(-) <-> CuL(+)) decreased from 2.9 +/- 0.1 at pH 3.5 to 2.5 +/- 0.1 at pH 5.5 (ionic strength I = 0.1). This behavior is in apparent contradiction with basic thermodynamics, as usually the higher the pH the more cations bind. Our combined titration, circular dichroism and dynamic light scattering study indicated that the change observed in Cu bond strength relates to a conformational change of the structure of xanthan, which generates more chelating sites at pH 3.5 than at pH 5.5. This hypothesis was validated by the fact that the Cu sorption constants on xanthan were always higher than those measured on a mixture of pyruvic and glucuronic acids (logK = 2.2), which are the two constitutive ligands present in the xanthan monomer. This study shows the role of the structural conformation of natural biopolymers in metal bond strength. This finding may help to better predict the fate of Cu and other metals in acidic environmental settings such as aquatic media affected by acid mine drainage, as well as peats and acidic soils, and to better define optimal conditions for bioremediation processes. PMID- 26824428 TI - The Emerging Role of Health Literacy in Chronic Disease Management: The Response to a Call for Action in Canada. PMID- 26824429 TI - Bundled strategies against infection after liver transplantation: Lessons from multidrug-resistant Pseudomonas aeruginosa. AB - Infection is a life-threatening complication after liver transplantation (LT). A recent outbreak of multidrug-resistant Pseudomonas aeruginosa triggered changes in our infection control measures. This study investigated the usefulness of our bundled interventions against postoperative infection after LT. This before-and after analysis enrolled 130 patients who underwent living donor or deceased donor LT between January 2011 and October 2014. We initiated 3 measures after January 2013: (1) we required LT candidates to be able to walk independently; (2) we increased the hand hygiene compliance rate and contact precautions; and (3) we introduced procalcitonin (PCT) measurement for a more precise determination of empirical antimicrobial treatment. We compared factors affecting the emergence of drug-resistant microorganisms, such as the duration of antimicrobial and carbapenem therapy and hospital stay, and outcomes such as bacteremia and death from infection between before (n = 77) and after (n = 53) the LT suspension period. The utility of PCT measurement was also evaluated. Patients' backgrounds were not significantly different before and after the protocol revision. Incidence of bacteremia (44% versus 25%; P = 0.02), detection rate of multiple bacteria (18% versus 4%; P = 0.01), and deaths from infections (12% versus 2%; P = 0.04) significantly decreased after the protocol revision. Duration of antibiotic (42.3 versus 25.1 days; P = 0.002) and carbapenem administration (15.1 versus 5.2 days; P < 0.001) and the length of postoperative hospital stay (85.4 versus 63.5 days; P = 0.048) also decreased after the protocol revision. PCT mean values were significantly higher in the bacteremia group (10.10 ng/mL), compared with the uneventful group (0.65 ng/mL; P = 0.002) and rejection group (2.30 ng/mL; P = 0.02). One-year overall survival after LT significantly increased in the latter period (71% versus 94%; P = 0.001). In conclusion, the bundled interventions were useful in preventing infections and lengthening overall survival after LT. PMID- 26824430 TI - Hybrid Top-Down/Bottom-Up Strategy Using Superwettability for the Fabrication of Patterned Colloidal Assembly. AB - Superwettability of substrates has had a profound influence on the production of novel and advanced colloidal assemblies in recent decades owing to its effect on the spreading area, evaporation rate, and the resultant assembly structure. In this paper, we investigated in detail the influence of the superwettability of a transfer/template substrate on the colloidal assembly from a hybrid top down/bottom-up strategy. By taking advantage of a superhydrophilic flat transfer substrate and a superhydrophobic groove-structured silicon template, the patterned colloidal microsphere assembly was formed including linear and mesh-, cyclic-, and multistopband assembly arrays of microspheres, and the optic waveguide of a circular colloidal structure was demonstrated. We believed this liquid top-down/bottom-up strategy would open an efficient avenue for assembling/integrating microspheres building blocks into device applications in a low-cost manner. PMID- 26824431 TI - Characterization of hepatic and cardiac iron deposition during standard treatment of anaemia in haemodialysis. AB - BACKGROUND: Parenteral iron is integral in the treatment of anaemia of chronic kidney disease patients on haemodialysis (HD). However, increased liver iron concentration (LIC) can result from such treatment, and this correlates poorly with serum ferritin or transferrin saturation values. It is unclear whether increased cardiac iron concentration also occurs in this setting. We aimed to evaluate the relationship of intravenous iron supplementation to hepatic and cardiac iron deposition in chronic HD subjects. METHODS: A cohort of 10 patients on chronic HD for at least 1 year underwent MRI-based quantitation of hepatic and cardiac iron content to evaluate the relationship between intravenous iron supplements and hepatic and cardiac iron deposition. The results were compared against the cumulative parenteral iron dose and serum iron markers. RESULTS: The median age was 61 years (95% confidence interval (CI) 50-71), HD time 2.5 years (95%CI 2.0-5.3) and cumulative iron dose 4300 mg (95%CI 2110-9045). Hepatic iron concentration was elevated in eight of 10 subjects (median 46 mmol/kg, range 31 76). Cardiac iron levels were within the reference range in all subjects. There was poor correlation between conventional haematinic values and either LIC or cardiac iron levels. None of the study subjects exhibited elevated cardiac iron concentration. CONCLUSION: Whilst HD patients receiving standard parenteral iron therapy have elevated LICs, this is not associated with cardiac iron deposition. Transferrin saturation and serum ferritin levels are poor markers of either liver or cardiac iron deposition in HD subjects. PMID- 26824432 TI - A Biophysical Model of CRISPR/Cas9 Activity for Rational Design of Genome Editing and Gene Regulation. AB - The ability to precisely modify genomes and regulate specific genes will greatly accelerate several medical and engineering applications. The CRISPR/Cas9 (Type II) system binds and cuts DNA using guide RNAs, though the variables that control its on-target and off-target activity remain poorly characterized. Here, we develop and parameterize a system-wide biophysical model of Cas9-based genome editing and gene regulation to predict how changing guide RNA sequences, DNA superhelical densities, Cas9 and crRNA expression levels, organisms and growth conditions, and experimental conditions collectively control the dynamics of dCas9-based binding and Cas9-based cleavage at all DNA sites with both canonical and non-canonical PAMs. We combine statistical thermodynamics and kinetics to model Cas9:crRNA complex formation, diffusion, site selection, reversible R-loop formation, and cleavage, using large amounts of structural, biochemical, expression, and next-generation sequencing data to determine kinetic parameters and develop free energy models. Our results identify DNA supercoiling as a novel mechanism controlling Cas9 binding. Using the model, we predict Cas9 off-target binding frequencies across the lambdaphage and human genomes, and explain why Cas9's off-target activity can be so high. With this improved understanding, we propose several rules for designing experiments for minimizing off-target activity. We also discuss the implications for engineering dCas9-based genetic circuits. PMID- 26824434 TI - Effect of heat waves on morbidity and mortality due to Parkinson's disease in Madrid: A time-series analysis. AB - BACKGROUND: Parkinson's disease (PD) is one of the factors which are associated with a higher risk of mortality during heat waves. The use of certain neuroleptic medications to control some of this disease's complications would appear to be related to an increase in heat-related mortality. OBJECTIVE: To analyse the relationship and quantify the short-term effect of high temperatures during heat wave episodes in Madrid on daily mortality and PD-related hospital admissions. METHODS: We used an ecological time-series study and fit Poisson regression models. We analysed the daily number of deaths due to PD and the number of daily PD-related emergency hospital admissions in the city of Madrid, using maximum daily temperature ( degrees C) as the main environmental variable and chemical air pollution as covariates. We controlled for trend, seasonalities, and the autoregressive nature of the series. RESULTS: There was a maximum daily temperature of 30 degrees C at which PD-related admissions were at a minimum. Similarly, a temperature of 34 degrees C coincides with an increase in the number of admissions. For PD-related admissions, the Relative Risk (RR) for every increase of 1 degrees C above the threshold temperature was 1.13 IC95%:(1.03 1.23) at lags 1 and 5; and for daily PD-related mortality, the RR was 1.14 IC95%:(1.01-1.28) at lag 3. CONCLUSION: Our results indicate that suffering from PD is a risk factor that contributes to the excess morbidity and mortality associated with high temperatures, and is relevant from the standpoint of public health prevention plans. PMID- 26824433 TI - In Vivo Transplantation of Enteric Neural Crest Cells into Mouse Gut; Engraftment, Functional Integration and Long-Term Safety. AB - OBJECTIVES: Enteric neuropathies are severe gastrointestinal disorders with unsatisfactory outcomes. We aimed to investigate the potential of enteric neural stem cell therapy approaches for such disorders by transplanting mouse enteric neural crest cells (ENCCs) into ganglionic and aganglionic mouse gut in vivo and analysing functional integration and long-term safety. DESIGN: Neurospheres generated from yellow fluorescent protein (YFP) expressing ENCCs selected from postnatal Wnt1-cre;R26R-YFP/YFP murine gut were transplanted into ganglionic hindgut of wild-type littermates or aganglionic hindgut of Ednrbtm1Ywa mice (lacking functional endothelin receptor type-B). Intestines were then assessed for ENCC integration and differentiation using immunohistochemistry, cell function using calcium imaging, and long-term safety using PCR to detect off target YFP expression. RESULTS: YFP+ ENCCs engrafted, proliferated and differentiated into enteric neurons and glia within recipient ganglionic gut. Transplanted cells and their projections spread along the endogenous myenteric plexus to form branching networks. Electrical point stimulation of endogenous nerve fibres resulted in calcium transients (F/F0 = 1.16 +/- 0.01;43 cells, n = 6) in YFP+ transplanted ENCCs (abolished with TTX). Long-term follow-up (24 months) showed transplanted ENCCs did not give rise to tumours or spread to other organs (PCR negative in extraintestinal sites). In aganglionic gut ENCCs similarly spread and differentiated to form neuronal and glial networks with projections closely associated with endogenous neural networks of the transition zone. CONCLUSIONS: Transplanted ENCCs successfully engrafted into recipient ganglionic and aganglionic gut showing appropriate spread, localisation and, importantly, functional integration without any long-term safety issues. This study provides key support for the development and use of enteric neural stem cell therapies. PMID- 26824436 TI - Diabetes Technology. AB - Diabetes technology is an evolving field. The research started with the development of blood glucose meters for patient self-testing and the introduction of insulin pen injection devices. Modern devices employ new technological features, such as the use of computer simulations and mathematical algorithms, connectivity and signal transfer, and the use of modern (space research-derived) materials. With these innovations, the goal to develop an artificial pancreas by closing the loop between a continuous glucose sensor and a continuous insulin delivering device via insulin delivery algorithms is coming closer to reality. As a consequence, interim achievements on this way result in the commercialization of innovative new diabetes technology devices, which help to facilitate the daily life of the affected people with diabetes. PMID- 26824435 TI - Associations between Metabolic Risk Factors and the Hypothalamic Volume in Childhood Leukemia Survivors Treated with Cranial Radiotherapy. AB - Metabolic complications are prevalent in individuals treated with cranial radiotherapy (CRT) for childhood acute lymphoblastic leukemia (ALL). The hypothalamus is a master regulator of endocrine and metabolic control. The aim of this study was to investigate whether the hypothalamic volume would be associated to metabolic parameters in ALL survivors. Thirty-eight (21 women) survivors participated in this study 34 years after diagnosis and with a median age of 38 (27-46) years. All were treated with a median CRT dose of 24 Gy and 11 years (3 13) of complete hormone supplementation. Comparisons were made to 31 matched controls. We performed analyses of fat mass, fat free mass, plasma (p)-glucose, p insulin, Homa-Index (a measure of insulin resistance), serum (s)-leptin, s ghrelin and of the hypothalamic volume in scans obtained by magnetic resonance imaging (MRI) at 3 Tesla. Serum leptin/kg fat mass (r = -0.4, P = 0.04) and fat mass (r = -0.4, P = 0.01) were negatively correlated with the HT volume among ALL survivors, but not among controls. We also detected significantly higher BMI, waist, fat mass, p-insulin, Homa-Index, leptin/kg fat mass and s-ghrelin and significantly lower fat free mass specifically among female ALL survivors (all P<0.01). Interestingly, s-ghrelin levels increased with time since diagnosis and with low age at diagnosis for childhood ALL. Our results showed that leptin/kg fat mass and fat mass were associated with a reduced HT volume 34 years after ALL diagnosis and that women treated with CRT after ALL are at high risk of metabolic abnormalities. Taken together our data suggest that the hypothalamus is involved in the metabolic consequences after CRT in ALL survivors. PMID- 26824437 TI - The auditory phenotype of children harboring mutations in the prestin gene. AB - Conclusion Auditory phenotypes of two children harboring prestin gene mutations were congenital or pre-lingual onset, moderate to profound, slowly progressive or non-progressive, and audiograms with either flat configuration or prominently elevated thresholds at middle and high frequencies. Objectives Despite the essential role of the prestin gene in hearing, only one mutation in two families and a missense variant in a family had been reported previously before our study reporting another family. The purpose of this study was to characterize auditory phenotypes in children recently found to harbor novel mutations in the prestin gene. Methods The subjects were two sisters with bilateral sensorineural hearing loss who were compound heterozygotes for c.209G > A (p.W70X) and c.390A > C (p.R130S) mutations in the prestin gene. Clinical history and auditory test results were collected and analyzed. Results Hearing loss was present from birth in the younger sister and occurred before 6 years of age in the elder sister. The degree of hearing loss was profound in the elder sister with little progression, and moderate in the younger sister with no progression. The audiogram of the elder sister showed prominently elevated thresholds at middle and high frequencies, while that of the younger sister demonstrated a flat configuration. PMID- 26824438 TI - The Prevalence of Huntington's Disease. AB - BACKGROUND: Reviews of the epidemiology of Huntington's disease (HD) suggest that its worldwide prevalence varies widely. This review was undertaken to confirm these observations, to assess the extent to which differences in case ascertainment and/or diagnosis might be responsible, and to investigate whether the prevalence pattern has changed over the past 50 years. METHODS: Eighty two relevant studies were identified from Medline and Embase, previous reviews, scrutiny of references from included and excluded studies and enquiry among those interested in the field. RESULTS: The lowest rates were among the Asians and the highest among the Caucasians. The differences are not fully explained by varying approaches to case-ascertainment or diagnosis. There was evidence of an increasing prevalence of between 15 and 20% per decade in studies from Australia, North America and Western Europe. CONCLUSIONS: The prevalence of HD varies more than tenfold between different geographical regions. This variation can in part be attributed to differences in case-ascertainment and/or diagnostic criteria, but there is consistent evidence of a lower incidence in Asian populations. There is also evidence that in Australia, North America and in Western Europe (including the United Kingdom), prevalence has increased over the past 50 plus years. PMID- 26824439 TI - Genetics of Type 2 Diabetes. AB - Genetic and environmental factors as well as their interactions contribute to the pathogenesis of type 2 diabetes. Linkage analysis, candidate gene approaches, genome-wide association studies, and sequencing have been used in the identification of common, low-frequency and rare variants for type 2 diabetes. Genome-wide association studies have identified >80 common variants for type 2 diabetes, with small effect sizes (risk of type 2 diabetes increased by 5-40%). Almost all of these variants regulate insulin secretion, and only a few regulate insulin sensitivity. Common variants capture only ~10% of the heritability of type 2 diabetes. Low-frequency and rare variants with large effects have also been identified, but their contribution to 'missing heritability' at the population level is limited. Gene-environment and gene-gene interactions and epigenetics are likely to contribute to the missing heritability of type 2 diabetes. Epigenetic factors (DNA methylations and histone modifications) are especially important because they might mediate the effects of environmental exposures on the risk of type 2 diabetes. Although understanding of the genetics of type 2 diabetes has exhibited great progress in the past few years, a substantial amount of additional work will be required to identify causal variants/genes and molecular mechanisms via which the association signals found confer diabetes risk. PMID- 26824440 TI - Regulatory aspects of VCA in Eurotransplant. AB - Vascularized composite allografts (VCAs) are a growing field within the area of transplantation. In 2014, the birth of a healthy baby after a successful uterus transplant from a living donor was reported in Sweden. VCAs are not specifically mentioned in any of the transplant acts of the Eurotransplant (ET) member states, which all belong to the European Union (EU). The Competent Authorities (CA) of the EU decided in 2012 that VCAs are to be regarded as organs. At the moment, there are no general guidelines in the ET area concerning wait list registration, allocation, procurement and transplantation, and also no regulations concerning reimbursement. To further develop this aspect, common policies and guidelines within the ET member states have to be developed. PMID- 26824442 TI - Marathon: An Open Source Software Library for the Analysis of Markov-Chain Monte Carlo Algorithms. AB - We present the software library marathon, which is designed to support the analysis of sampling algorithms that are based on the Markov-Chain Monte Carlo principle. The main application of this library is the computation of properties of so-called state graphs, which represent the structure of Markov chains. We demonstrate applications and the usefulness of marathon by investigating the quality of several bounding methods on four well-known Markov chains for sampling perfect matchings and bipartite graphs. In a set of experiments, we compute the total mixing time and several of its bounds for a large number of input instances. We find that the upper bound gained by the famous canonical path method is often several magnitudes larger than the total mixing time and deteriorates with growing input size. In contrast, the spectral bound is found to be a precise approximation of the total mixing time. PMID- 26824443 TI - US to Offer Uterus Transplants. PMID- 26824441 TI - BMP-7 Treatment Increases M2 Macrophage Differentiation and Reduces Inflammation and Plaque Formation in Apo E-/- Mice. AB - Inflammation plays a fundamental role in the inception and development of atherosclerosis (ATH). Mechanisms of inflammation include the infiltration of monocytes into the injured area and subsequent differentiation into either pro inflammatory M1 macrophages or anti-inflammatory M2 macrophages. We have previously published data suggesting bone morphogenetic protein-7 (BMP-7) enhances M2 macrophage differentiation and anti-inflammatory cytokine secretion in vitro. In this regard, we hypothesized BMP-7 would inhibit plaque formation in an animal model of ATH through monocytic plasticity mediation. ATH was generated in male and female Apo E(-/-) mice via partial left carotid artery (PLCA) ligation and mice were divided into 3 groups: Sham, PLCA, and PLCA+BMP-7 (200 ug/kg; i.v.). Our data suggest that BMP-7 inhibits plaque formation and increases arterial systolic velocity. Furthermore, we report inhibition of monocyte infiltration and a decrease in associated pro-inflammatory cytokines (MCP-1, TNF alpha, and IL-6) in the PLCA+BMP-7 mice. In contrast, our data suggest a significant (p<0.05) increase in M2 macrophage populations with consequential enhanced anti-inflammatory cytokine (IL-1RA, IL-10, and Arginase 1) expression following BMP-7 treatment. We have also observed that mechanisms promoting monocyte into M2 macrophage differentiation by BMP-7 involve the upregulation and activation of the BMP-7 receptor (BMP-7RII). In conclusion, we report that BMP-7 has the potential to mediate cellular plasticity and mitigate the inflammatory immune response, which results in decreased plaque formation and improved blood velocity. PMID- 26824447 TI - Chest Wall Mass 5 Years After Liver Transplantation. PMID- 26824445 TI - Immunosuppressive Medications and Squamous Cell Skin Carcinoma: Nested Case Control Study Within the Skin Cancer after Organ Transplant (SCOT) Cohort. AB - Organ transplant recipients (OTRs) have a substantially elevated risk of squamous cell skin carcinoma (SCSC), largely attributed to immunosuppressive medications used to prevent graft rejection, although data to support the role of newer drugs in SCSC risk are sparse. We investigated the association between immunosuppressive medications and SCSC risk among cardiac and renal transplant recipients in the SCOT cohort study. Incident cases were ascertained through medical record review after self-report of skin biopsy (n = 170). Controls without SCSC (n = 324) were matched to cases on sex, age, race, transplant year, hospital, donor type, organ transplanted, and time between transplantation and interview. Conditional logistic regression was used to evaluate the association between specific medications and SCSC. Users of the antimetabolite azathioprine were more than twice as likely to develop SCSC (odds ratio [OR] = 2.67, 95% confidence interval [CI] 1.23-5.76). In contrast, the newer antimetabolite preparations (i.e., mycophenolic acid [MPA]) were associated with lower SCSC risk (OR = 0.45, 95% CI 0.29-0.69). This inverse association between MPA and SCSC persisted among OTRs with no history of azathioprine use, even after adjustment for simultaneous use of the calcineurin inhibitor tacrolimus (OR = 0.52, 95% CI 0.32-0.84). Our data suggest that the increased risk of SCSC historically associated with azathioprine is not seen in OTRs prescribed newer regimens, including MPA and tacrolimus. PMID- 26824448 TI - The importance of nutrition for health in patients with transfusion-dependent thalassemia. AB - Nutrition is increasingly being seen by care providers as important for patients with thalassemia. However, the definition of optimal nutritional support and the means to provide that support remain elusive. This review focuses on the relationships between nutritional status and three common comorbidities in patients with thalassemia: low bone mass, growth deficiency, and diabetes. The association between low bone mass and specific nutrient deficiencies (e.g., vitamin D, zinc) is clear, while the role of nutritional adequacy for young patients with growth deficiencies requires careful analysis to distinguish it from chronic anemia and endocrine insufficiency. Correction of isolated nutritional deficiencies in small cohorts of patients with thalassemia has shown some promise at improving both bone health and linear growth in the short term. However, the long-term safety and acceptability of these practices need to be evaluated. On the whole, there are few well-designed, adequately powered studies of the role of general dietary or specific micronutrients in the cause, treatment, or prevention of these commonly observed morbidities in thalassemia. Until these data are gathered, it is suggested that patients with thalassemia be monitored frequently and that their nutritional deficiencies be corrected when observed in order to advance their overall health and quality of life. PMID- 26824449 TI - Aromatic-Mediated Carbohydrate Recognition in Processive Serratia marcescens Chitinases. AB - Microorganisms use a host of enzymes, including processive glycoside hydrolases, to deconstruct recalcitrant polysaccharides to sugars. Processive glycoside hydrolases closely associate with polymer chains and repeatedly cleave glycosidic linkages without dissociating from the crystalline surface after each hydrolytic step; they are typically the most abundant enzymes in both natural secretomes and industrial cocktails by virtue of their significant hydrolytic potential. The ubiquity of aromatic residues lining the enzyme catalytic tunnels and clefts is a notable feature of processive glycoside hydrolases. We hypothesized that these aromatic residues have uniquely defined roles, such as substrate chain acquisition and binding in the catalytic tunnel, that are defined by their local environment and position relative to the substrate and the catalytic center. Here, we investigated this hypothesis with variants of Serratia marcescens family 18 processive chitinases ChiA and ChiB. We applied molecular simulation and free energy calculations to assess active site dynamics and ligand binding free energies. Isothermal titration calorimetry provided further insight into enthalpic and entropic contributions to ligand binding free energy. Thus, the roles of six aromatic residues, Trp-167, Trp-275, and Phe-396 in ChiA, and Trp 97, Trp-220, and Phe-190 in ChiB, have been examined. We observed that point mutation of the tryptophan residues to alanine results in unfavorable changes in the free energy of binding relative to wild-type. The most drastic effects were observed for residues positioned at the "entrances" of the deep substrate-binding clefts and known to be important for processivity. Interestingly, phenylalanine mutations in ChiA and ChiB had little to no effect on chito-oligomer binding, in accordance with the limited effects of their removal on chitinase functionality. PMID- 26824450 TI - Re: "A National Evaluation of the Scholarly Activity Requirement in Residency Programs: A Survey of Emergency Medicine Program Directors". PMID- 26824451 TI - TOB1 Deficiency Enhances the Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Tendon-Bone Healing in a Rat Rotator Cuff Repair Model. AB - BACKGROUND/AIMS: This study investigated the effect of silencing TOB1 (Transducer of ERBB2, 1) expression in bone marrow-derived mesenchymal stem cells (MSCs) on MSC-facilitated tendon-bone healing in a rat supraspinatus repair model. METHODS: Rat MSCs were transduced with a recombinant lentivirus encoding short hairpin RNA (shRNA) against TOB1. MSC cell proliferation was analyzed by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. The effect of MSCs with TOB1 deficiency on tendon-bone healing in a rat rotator cuff repair model was evaluated by biomechanical testing, histological analysis and collagen type I and II gene expression. An upstream regulator (miR-218) of TOB1 was determined in MSCs. RESULTS: We found that knockdown of TOB1 significantly increased the proliferative activity of rat MSCs in vitro. When MSCs with TOB1 deficiency were injected into injured rat supraspinatus tendon-bone junctions, the effect on tendon-bone healing was enhanced compared to treatment with control MSCs with normal TOB1 expression, as evidenced by elevated levels of ultimate load to failure and stiffness, increased amount of fibrocartilage and augmented expression of collagen type I and type II genes. In addition, we found that the TOB1 3' untranslated region is a direct target of miR-218. Similar to the effect of TOB1 deficiency, overexpression of miR-218 effectively promoted tendon-bone healing in rat. CONCLUSION: These results suggest that TOB1 may play a negative role in the effect of MSCs on tendon-bone healing, and imply that expression of TOB1 may be regulated by miR-218. PMID- 26824452 TI - TIPE2 Alleviates Systemic Lupus Erythematosus Through Regulating Macrophage Polarization. AB - BACKGROUND/AIMS: We have recently shown that macrophage polarization may alter the pathogenesis and severity of systemic lupus erythematosus (SLE). However, a practical approach to modulate macrophage polarization in vivo is so far not available. In the current study, we aimed to use tumor necrosis factor (TNF) alpha-induced protein 8-like 2 (TIPE2) to regulate macrophage polarization in vitro and in vivo, and to study the effects on experimental SLE. METHODS: We prepared adeno-associated virus carrying TIPE2 (AAV-TIPE2). We induced experimental SLE in mice with an activated lymphocyte-derived DNA (ALD-DNA) method. We examined the effects of TIPE2 overexpression on macrophage polarization in vitro, and in vivo in the SLE model. We also examined the effects of TIPE2 overexpression on the severity of SLE, by serum anti-dsDNA autoantibody, renal pathological changes, and urine protein levels. RESULTS: ALD-DNA induced SLE-like features in mice, manifested by induction of serum anti-dsDNA autoantibody, renal pathological changes, and increases in urine protein levels. TIPE2 overexpression by AAV-TIPE2 induced macrophage polarization to a M2 phenotype, in vitro and in vivo in the SLE mouse model. TIPE2 overexpression significantly decreased SLE severity. CONCLUSION: TIPE2 alleviates experimental SLE through induction of macrophage polarization to a M2 phenotype, which may be used as a promising therapeutic strategy for treating SLE. PMID- 26824453 TI - Nucleosome Assembly Protein 1-Like 1 (Nap1l1) Regulates the Proliferation of Murine Induced Pluripotent Stem Cells. AB - BACKGROUND/AIMS: To investigate whether nucleosome assembly protein 1-like 1 (Nap1l1) regulates the proliferation of induced pluripotent stem cells (iPSC) and the potential mechanisms. METHODS: Nap1l1-knockdown-iPSC and Nap1l1 overexpression-iPSC were constructed by transfection of lentiviral particles. The proliferation of iPSC was detected by MTT analysis, and cell cycle was analyzed by flow cytometry. RESULTS: Nap1l1 overexpression promoted iPSC proliferation and induced G2/M transition compared to their control iPSC while Nap1l1-knockdown iPSC dramatically displayed the reduced proliferation and accumulated G2/M phase cells. Further analysis showed that Nap1l1 overexpression in iPSC increased the expression of cyclin B1, downregulated the expression of p21 and p27, while knockdown of Nap1l1 showed the opposite effects. In addition, overexpression of Nap1l1 promoted the phosphorylation of AKT and ERK in iPSC, while knockdown of Nap1l1 inhibited the effects. However, these effects displayed in Nap1l1 overexpression-iPSC were greatly suppressed by the inhibition of AKT or ERK signaling. CONCLUSIONS: The results indicate that Nap1l1 promotes the proliferation of iPSC attributable to G2/M transition caused by downregulation of p27 and p21, and upregulation of cyclin B1, the activation of AKT or ERK is involved in the process. The present study has revealed a novel molecular mechanism involved in the proliferation of iPSC. PMID- 26824454 TI - Placental Growth Factor Promotes Ovarian Cancer Cell Invasion via ZEB2. AB - BACKGROUND/AIMS: The aggressive manner of ovarian cancer (OVC) cells accounts for the majority of its lethality. Recently, we have shown that placental growth factor (PLGF) promotes metastases of OVC cells through miR-543-regulated MMP7. In the current study, we analyzed the effects of PLGF on another cell invasion associated protein, ZEB2, in OVC cells. METHODS: The PLGF and ZEB2 levels in OVC tissues were compared to the paired adjacent non-tumor ovary tissue. We modified ZEB2 levels in OVC cells, and examined its effects on PLGF mRNA and protein levels by RT-qPCR and by Western blot, respectively. We also modified PLGF levels in OVC cells, and examined its effects on ZEB2 mRNA and protein levels by RT-qPCR and by Western blot, respectively. Then, we examined the cell invasiveness in PLGF-modified OVC cells in a transwell cell invasion assay. Finally, we used specific signal pathway inhibitors to treat PLGF-modified OVC cells and examined the effects on ZEB2 activation. RESULTS: PLGF and ZEB2 levels were both significantly increased in OVC tissues, compared to the paired adjacent non-tumor ovary tissue. The PLGF and ZEB2 levels were strongly correlated. ZEB2 modification did not alter PLGF levels. Overexpression of PLGF in OVC cells significantly increased ZEB2 levels and cell invasiveness, while PLGF depletion in OVC cells significantly decreased ZEB2 levels and cell invasiveness. Application of a specific MAPK-p38 inhibitor, but not application of specific inhibitors for MAPK-p42/p44, PI3k/Akt, or JNK signaling pathways, to PLGF overexpressing OVC cells substantially abolished the PLGF-induced ZEB2 activation. CONCLUSION: PLGF enhances OVC cell invasion through MAPK-p38 dependent activation of ZEB2. PMID- 26824455 TI - SGK3 Sensitivity of Voltage Gated K+ Channel Kv1.5 (KCNA5). AB - BACKGROUND: The serum & glucocorticoid inducible kinase isoform SGK3 is a powerful regulator of several transporters, ion channels and the Na+/K+ ATPase. Targets of SGK3 include the ubiquitin ligase Nedd4-2, which is in turn a known regulator of the voltage gated K+ channel Kv1.5 (KCNA5). The present study thus explored whether SGK3 modifies the activity of the voltage gated K+ channel KCNA5, which participates in the regulation of diverse functions including atrial cardiac action potential, activity of vascular smooth muscle cells, insulin release and tumour cell proliferation. METHODS: cRNA encoding KCNA5 was injected into Xenopus oocytes with and without additional injection of cRNA encoding wild type SGK3, constitutively active S419DSGK3, inactive K191NSGK3 and/or wild type Nedd4-2. Voltage gated K+ channel activity was quantified utilizing dual electrode voltage clamp. RESULTS: Voltage gated current in KCNA5 expressing Xenopus oocytes was significantly enhanced by wild-type SGK3 and S419DSGK3, but not by K191NSGK3. SGK3 was effective in the presence of ouabain (1 mM) and thus did not require Na+/K+ ATPase activity. Coexpression of Nedd4-2 decreased the voltage gated current in KCNA5 expressing Xenopus oocytes, an effect largely reversed by additional coexpression of SGK3. CONCLUSION: SGK3 is a positive regulator of KCNA5, which is at least partially effective by abrogating the effect of Nedd4-2. PMID- 26824456 TI - The Long Non-Coding RNA ENST00000537266 and ENST00000426615 Influence Papillary Thyroid Cancer Cell Proliferation and Motility. AB - BACKGROUND/AIMS: Papillary thyroid cancer (PTC) is the most common histotype of Thyroid cancer (TC). Here, we detected the differentially expressed lncRNAs in tumor tissues and non-tumor tissues of PTC patients by lncRNA microarrays, and explored the function and molecular mechanisms of lncRNAs in the pathogenesis of PTC using a PTC cell line. METHODS: CCK-8 assay, colony formation assay and EdU assay were used to detect the cell viability. Flow Cytometry was used to detect the cell cycle and apoptosis. Transwell and scratch assay were used to detect the cell motility. RESULTS: CCK-8 assay, colony formation assay and EdU assay revealed that lncRNAs (ENST00000537266 and ENST00000426615) could inhibit cell proliferation. Cell cycle analysis showed that cell proportion was statistically significant increased in G1 phase and decreased in S phase and G2 phase in Si-266 transfected TPC-1 cells. In addition, a noteworthy increase of cell proportion in G1 phase accompanied by a decrease in S phase and unchanged G2 phase in Si-615 transfected TPC-1 cells were also observed. Meanwhile, transwell and scratch assay showed that ENST00000426615 could inhibit the cell motility while ENST00000537266 could not. CONCLUSION: Our results showed that lncRNAs (ENST00000426615 and ENST00000537266) might be important regulators of PTC cell proliferation and motility, which might provide new insight into the understanding of PTC pathogenesis. PMID- 26824457 TI - Nocodazole Induced Suicidal Death of Human Erythrocytes. AB - BACKGROUND: The microtubule assembly inhibitor nocodazole has been shown to trigger caspase-independent mitotic death and caspase dependent apoptosis. Similar to apoptosis of nucleated cells, erythrocytes may undergo eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress and ceramide. The present study explored, whether and how nocodazole induces eryptosis. METHODS: Flow cytometry was employed to determine phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, the abundance of reactive oxygen species (ROS) from 2',7'-dichlorodihydrofluorescein (DCF) diacetate dependent fluorescence as well as ceramide surface abundance utilizing specific antibodies. Tubulin abundance was quantified by TubulinTrackerTM Green reagent and visualized by confocal microscopy. RESULTS: A 48 hours exposure of human erythrocytes to nocodazole (>= 30 ug/ml) significantly increased the percentage of annexin-V-binding cells without significantly modifying average forward scatter. Nocodazole significantly increased Fluo3-fluorescence, significantly increased DCF fluorescence and significantly increased ceramide surface abundance. The effect of nocodazole on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+ and was not modified in the presence of Caspase 3 inhibitor zVAD (1 uM). Nocodazole treatment reduced the content of total tubulin. CONCLUSIONS: Nocodazole triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to stimulation of Ca2+ entry, oxidative stress and ceramide. PMID- 26824458 TI - Pttg1 Promotes Growth of Breast Cancer through P27 Nuclear Exclusion. AB - BACKGROUND/AIMS: A role of Pituitary Tumor Transforming Gene 1 (Pttg1) in the carcinogenesis has been shown in some cancers, but not in BC (BC). METHODS: We compared the levels of Pttg1 in the resected BC tissue with the adjacent normal breast tissue from the same patient. We modified Pttg1 levels in a BC cell line, MCF7, by either a Pttg1 transgene, or a Pttg1 shRNA. The cell growth was measured in an MTT assay. The cell apoptosis was measured by apoptosis assay. The nuclear protein of cell-cycle-related genes was examined in Pttg1-modifed BC cells. Co immunoprecipitation was performed to examine the association of Pttg1 and p27. RESULTS: We detected significantly higher levels of Pttg1 in the resected BC tissue, compared to the adjacent normal breast tissue from the same patient. Overexpression or depletion of Pttg1 in MCF7 significantly increased or inhibited cell growth, respectively. Changes in Pttg1 levels, however, did not alter cell apoptosis, suggesting that Pttg1 increases cell growth through augmented cell proliferation, rather than decreased cell apoptosis. Among all examined cell cycle-related proteins in Pttg1-modifed BC cells, only nuclear p27 levels were significantly affected. Further, co-immunoprecipitation showed that Pttg1 directly associated with p27. CONCLUSION: Pttg1 may increase BC cell growth through nuclear exclusion of p27, which highlights a novel molecular regulatory machinery in tumorigenesis of BC. PMID- 26824459 TI - The Effects of Indoxyl Sulfate on Human Umbilical Cord-Derived Mesenchymal Stem Cells In Vitro. AB - BACKGROUND/AIMS: Indoxyl sulfate, an important protein-bound uremic toxin, can damage stem cells, thus hampering stem cell-based regenerative medicine approaches targeting chronic kidney diseases (CKD). Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are thought to have promising clinical application because of their high proliferative potential and ease of isolation than MSCs from other sources. In the present study, we aimed to determine the harmful effects of indoxyl sulfate on the phenotype and functional potential of hUC-MSCs in vitro. METHODS: The toxicity and cell viability was examined by Trypan blue exclusion and MTT assay. The cellular surface markers and the percentage of apoptotic cells by Annexin-V/PI staining were analyzed by flow cytometry. Proliferation was evaluated based on cell number counting and Ki-67 immunostaining. Cell senescence was measured using senescence-associated beta Galactosidase activity. The ability to stimulate the development of CD4+CD25+FoxP3+ regulatory T cells was assessed by incubating hUC-MSCs with peripheral blood mononuclear cells from the healthy volunteers. RESULTS: Our results demonstrated that the immunophenotype of hUC-MSCs was not affected by indoxyl sulfate flow cytometry. However, a significant decrease in cell numbers and fraction of Ki-67 positive proliferating cells, along with a significant increase in cellular senescence were detected in hUC-MSCs after exposure to indoxyl sulfate. Additionally, their ability to stimulate CD4+CD25+FoxP3+ regulatory T cell production was compromised when hUC-MSCs were pretreated with indoxyl sulfate. CONCLUSION: Taken together, our study clearly demonstrated that the molecular alterations and functional incompetence in hUC-MSCs under the challenge of indoxyl sulfate in vitro. PMID- 26824461 TI - User-customized brain computer interfaces using Bayesian optimization. AB - OBJECTIVE: The brain characteristics of different people are not the same. Brain computer interfaces (BCIs) should thus be customized for each individual person. In motor-imagery based synchronous BCIs, a number of parameters (referred to as hyper-parameters) including the EEG frequency bands, the channels and the time intervals from which the features are extracted should be pre-determined based on each subject's brain characteristics. APPROACH: To determine the hyper-parameter values, previous work has relied on manual or semi-automatic methods that are not applicable to high-dimensional search spaces. In this paper, we propose a fully automatic, scalable and computationally inexpensive algorithm that uses Bayesian optimization to tune these hyper-parameters. We then build different classifiers trained on the sets of hyper-parameter values proposed by the Bayesian optimization. A final classifier aggregates the results of the different classifiers. MAIN RESULTS: We have applied our method to 21 subjects from three BCI competition datasets. We have conducted rigorous statistical tests, and have shown the positive impact of hyper-parameter optimization in improving the accuracy of BCIs. Furthermore, We have compared our results to those reported in the literature. SIGNIFICANCE: Unlike the best reported results in the literature, which are based on more sophisticated feature extraction and classification methods, and rely on prestudies to determine the hyper-parameter values, our method has the advantage of being fully automated, uses less sophisticated feature extraction and classification methods, and yields similar or superior results compared to the best performing designs in the literature. PMID- 26824460 TI - Dopamine D1-Like Receptors Suppress the Proliferation of Macrophages Induced by Ox-LDL. AB - BACKGROUND/AIMS: Oxidized low-density lipoprotein (Ox-LDL) induces macrophage proliferation, a key physiological process which leads to atherosclerosis. The aim of this study was to determine the effects of dopamine D1-like receptors on macrophage proliferation induced by Ox-LDL. METHODS: The expression of dopamine D1-like receptors was determined by immunohistochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblotting. The effect of D1-like receptors on macrophage proliferation induced by Ox-LDL was measured by 3[H] thymidine incorporation and cell number count. RESULTS: Dopamine D1-like receptors were present in macrophages as determined by immunohistochemistry, RT PCR and immunoblotting. A D1-like receptor agonist, fenoldopam, which by itself had no effect on macrophage proliferation, inhibited the stimulatory effect of Ox LDL on macrophage proliferation. This was further confirmed by the D1-like receptor antagonist SCH 23390 blocking the effect of fenoldopam, thereby indicating that the fenoldopam action was receptor specific. Phosphatidylinositol 3-kinase (PI3K/Akt) and mitogen-activated protein kinase (MAPK/ERK) pathways were also involved in the proliferative effect of Ox-LDL because in the presence of PI3K/Akt or MAPK/ERK inhibitors, LY294002 or PD98059, the stimulatory effects of Ox-LDL were blocked. Moreover, the stimulatory effect of Ox-LDL on the phosphorylation of ERK and Akt was significantly reduced by fenoldopam in macrophages. Additional experiments found that both D1 and D5 receptor expression was lower in the peritoneal macrophages from Apolipoprotein E-deficient mice compared to the control C57Bl/6J mice. CONCLUSIONS: Macrophages express D1-like receptors. The activation of the D1-like receptors significantly inhibits Ox-LDL induced macrophage proliferation, possibly through the inhibition of the PI3K/Akt and MAPK/ERK signaling pathways. PMID- 26824462 TI - Nonsteroidal Anti-inflammatory-Organometallic Anticancer Compounds. AB - Compounds that combine metal-based drugs with covalently linked targeted organic agents have been shown, in some instances, to exhibit superior anticancer properties compared to the individual counterparts. Within this framework, we prepared a series of organometallic ruthenium(II)- and osmium(II)-p-cymene complexes modified with the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin and diclofenac. The NSAIDs are attached to the organometallic moieties via monodentate (pyridine/phosphine) or bidentate (bipyridine) ligands, affording piano-stool Ru(II) and Os(II) arene complexes of general formula [M(eta(6)-p-cymene)Cl2(N)], where N is a pyridine-based ligand, {2-(2-(1-(4 chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetoxy)ethyl-3-(pyridin-3 yl)propanoate} or {2-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)ethyl-3 (pyridin-3-yl)propanoate}, [M(eta(6)-p-cymene)Cl2(P)], where P is a phosphine ligand, {2-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetoxy)ethyl 4-(diphenylphosphanyl)benzoate} or {2-(2-(2-((2,6 dichlorophenyl)amino)phenyl)acetoxy)ethyl-4-(diphenylphosphanyl)benzoate, and [M(eta(6)-p-cymene)Cl(N,N')][Cl], where N,N' is a bipyridine-based ligand, (4' methyl-[2,2'-bipyridin]-4-yl)methyl-2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H indol-3-yl)acetate), (4'-methyl-[2,2'-bipyridin]-4-yl)methyl-2-(2-((2,6 dichlorophenyl)amino)phenyl)acetate), (bis(2-(2-(1-(4-chlorobenzoyl)-5-methoxy-2 methyl-1H-indol-3-yl)acetoxy)ethyl)[2,2'-bipyridine]-5,5'-dicarboxylate), or (bis(2-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)ethyl)[2,2'-bipyridine] 5,5'-dicarboxylate). The antiproliferative properties of the complexes were assessed in human ovarian cancer cells (A2780 and A2780cisR, the latter being resistant to cisplatin) and nontumorigenic human embryonic kidney (HEK-293) cells. Some of the complexes are considerably more cytotoxic than the original drugs and also display significant cancer cell selectivity. PMID- 26824463 TI - Gender identity, healthcare access, and risk reduction among Malaysia's mak nyah community. AB - Transgender women (TGW) face compounded levels of stigma and discrimination, resulting in multiple health risks and poor health outcomes. TGW identities are erased by forcing them into binary sex categories in society or treating them as men who have sex with men (MSM). In Malaysia, where both civil and religious law criminalise them for their identities, many TGW turn to sex work with inconsistent prevention methods, which increases their health risks. This qualitative study aims to understand how the identities of TGW sex workers shapes their healthcare utilisation patterns and harm reduction behaviours. In-depth, semi-structured interviews were conducted with 21 male-to-female transgender (mak nyah) sex workers in Malaysia. Interviews were transcribed, translated into English, and analysed using thematic coding. Results suggest that TGW identity is shaped at an early age followed by incorporation into the mak nyah community where TGW were assisted in gender transition and introduced to sex work. While healthcare was accessible, it failed to address the multiple healthcare needs of TGW. Pressure for gender-affirming health procedures and fear of HIV and sexually transmitted infection screening led to potentially hazardous health behaviours. These findings have implications for developing holistic, culturally sensitive prevention and healthcare services for TGW. PMID- 26824464 TI - A Review of Health Risks and Pathways for Exposure to Wastewater Use in Agriculture. AB - BACKGROUND: Wastewater is increasingly being used in the agricultural sector to cope with the depletion of freshwater resources as well as water stress linked to changing climate conditions. As wastewater irrigation expands, research focusing on the human health risks is critical because exposure to a range of contaminants must be weighed with the benefits to food security, nutrition and livelihoods. OBJECTIVES: The goal of this paper was to review research examining health risks and exposure pathways associated with wastewater irrigation to identify research trends and gaps. METHODS: We conducted a review of the literature and identified a total of 126 studies published from 1995 to 2013. Findings were summarized based on several themes including types of exposure pathways, wastewater contaminants, methodological approaches and the geographical distribution of research. RESULTS: Only 23 studies used epidemiological methods, while most research applied alternative methods to estimate risk, such as quantitative risk assessment models or comparisons of crop contamination to established guidelines for wastewater reuse. A geographic breakdown demonstrated a focus on microbiological contaminants in specific regions such as sub-Saharan Africa and Southeast Asia, despite growing chemical risks associated with rapid urbanization and industrialization that may change the types and distribution of wastewater contaminants. CONCLUSIONS: To provide a more comprehensive understanding of the health risks of wastewater use in agriculture, future research should consider multiple exposure routes, long-term health implications, and increase the range of contaminants studied, particularly in regions heavily dependent on wastewater irrigation. CITATION: Dickin SK, Schuster-Wallace CJ, Qadir M, Pizzacalla K. 2016. A review of health risks and pathways for exposure to wastewater use in agriculture. Environ Health Perspect 124:900-909; http://dx.doi.org/10.1289/ehp.1509995. PMID- 26824465 TI - Clinical Evaluation of an Affordable Qualitative Viral Failure Assay for HIV Using Dried Blood Spots in Uganda. AB - BACKGROUND: WHO recommends regular viral load (VL) monitoring of patients on antiretroviral therapy (ART) for timely detection of virological failure, prevention of acquired HIV drug resistance (HIVDR) and avoiding unnecessary switching to second-line ART. However, the cost and complexity of routine VL testing remains prohibitive in most resource limited settings (RLS). We evaluated a simple, low-cost, qualitative viral-failure assay (VFA) on dried blood spots (DBS) in three clinical settings in Uganda. METHODS: We conducted a cross sectional diagnostic accuracy study in three HIV/AIDS treatment centres at the Joint Clinical Research Centre in Uganda. The VFA employs semi-quantitative detection of HIV-1 RNA amplified from the LTR gene. We used paired dry blood spot (DBS) and plasma with the COBASAmpliPrep/COBASTaqMan, Roche version 2 (VLref) as the reference assay. We used the VFA at two thresholds of viral load, (>5,000 or >1,000 copies/ml). RESULTS: 496 paired VFA and VLref results were available for comparative analysis. Overall, VFA demonstrated 78.4% sensitivity, (95% CI: 69.7% 87.1%), 93% specificity (95% CI: 89.7%-96.4%), 89.3% accuracy (95% CI: 85%-92%) and an agreement kappa = 0.72 as compared to the VLref. The predictive values of positivity and negativity among patients on ART for >12 months were 72.7% and 99.3%, respectively. CONCLUSIONS: VFA allowed 89% of correct classification of VF. Only 11% of the patients were misclassified with the potential of unnecessary or late switch to second-line ART. Our findings present an opportunity to roll out simple and affordable VL monitoring for HIV-1 treatment in RLS. PMID- 26824467 TI - Language Identification in Short Utterances Using Long Short-Term Memory (LSTM) Recurrent Neural Networks. AB - Long Short Term Memory (LSTM) Recurrent Neural Networks (RNNs) have recently outperformed other state-of-the-art approaches, such as i-vector and Deep Neural Networks (DNNs), in automatic Language Identification (LID), particularly when dealing with very short utterances (~3s). In this contribution we present an open source, end-to-end, LSTM RNN system running on limited computational resources (a single GPU) that outperforms a reference i-vector system on a subset of the NIST Language Recognition Evaluation (8 target languages, 3s task) by up to a 26%. This result is in line with previously published research using proprietary LSTM implementations and huge computational resources, which made these former results hardly reproducible. Further, we extend those previous experiments modeling unseen languages (out of set, OOS, modeling), which is crucial in real applications. Results show that a LSTM RNN with OOS modeling is able to detect these languages and generalizes robustly to unseen OOS languages. Finally, we also analyze the effect of even more limited test data (from 2.25s to 0.1s) proving that with as little as 0.5s an accuracy of over 50% can be achieved. PMID- 26824466 TI - Determination of B-Cell Epitopes in Patients with Celiac Disease: Peptide Microarrays. AB - BACKGROUND: Most antibodies recognize conformational or discontinuous epitopes that have a specific 3-dimensional shape; however, determination of discontinuous B-cell epitopes is a major challenge in bioscience. Moreover, the current methods for identifying peptide epitopes often involve laborious, high-cost peptide screening programs. Here, we present a novel microarray method for identifying discontinuous B-cell epitopes in celiac disease (CD) by using a silicon-based peptide array and computational methods. METHODS: Using a novel silicon-based microarray platform with a multi-pillar chip, overlapping 12-mer peptide sequences of all native and deamidated gliadins, which are known to trigger CD, were synthesized in situ and used to identify peptide epitopes. RESULTS: Using a computational algorithm that considered disease specificity of peptide sequences, 2 distinct epitope sets were identified. Further, by combining the most discriminative 3-mer gliadin sequences with randomly interpolated3- or 6-mer peptide sequences, novel discontinuous epitopes were identified and further optimized to maximize disease discrimination. The final discontinuous epitope sets were tested in a confirmatory cohort of CD patients and controls, yielding 99% sensitivity and 100% specificity. CONCLUSIONS: These novel sets of epitopes derived from gliadin have a high degree of accuracy in differentiating CD from controls, compared with standard serologic tests. The method of ultra-high density peptide microarray described here would be broadly useful to develop high fidelity diagnostic tests and explore pathogenesis. PMID- 26824468 TI - A fortunate outcome after electrical cardioversion with a giant persistent left atrial thrombus. Is TOE-guided strategy more preferable in high risk patients? PMID- 26824469 TI - Field Observations of Questing and Dispersal by Colonized Nymphal Amblyomma maculatum Koch (Acari: Ixodidae). AB - : Almost nothing is known about the questing and dispersal behavior of immature Gulf Coast ticks (Amblyomma maculatum), a vector of both medical and veterinary concern. This experiment examined host-seeking (questing) and dispersal of marked, previously colonized, nymphal A. maculatum released in field plots in rural Oktibbeha County, Mississippi during 2015. A total of 500 (250 per replication) A. maculatum nymphs were painted and released in 5 plots (50 ticks each time). Observations were then made 5 times, approximately every 3 days, searching the plots for ticks from the release points outwards to 50 cm. Mean overall vertical questing height of ticks in Replication 1 in March (5.13 cm) was significantly higher than that of Replication 2 in April (2.57 cm) for a combined mean questing height of 3.58 cm. Ticks dispersed at a mean rate of 1.71 cm/day (Replication 1) and 0.98 cm/day (Replication 2), for an overall mean dispersal rate of 1.27 cm/day. When observation days where tick movement was impacted by adverse weather conditions were excluded, means between the replications were much closer. Only 38 of 2,500 possible total observations (1.5%) of the marked ticks were subsequently seen questing in this study, perhaps mirroring low questing rates of nymphal A. maculatum in nature. Additionally, 2 ticks were found in dense vegetation at the base of a plant. These data show that nymphs of this species disperse slowly, quest low to the ground, and can hide in very dense vegetation. PMID- 26824470 TI - Dynorphin A analogs for the treatment of chronic neuropathic pain. AB - Chronic pain is one of the most ubiquitous diseases in the world, but treatment is difficult with conventional methods, due to undesirable side effects of treatments and unknown mechanisms of pathological pain states. The endogenous peptide, dynorphin A has long been established as a target for the treatment of pain. Interestingly, this unique peptide has both inhibitory (opioid in nature) and excitatory activities (nonopioid) in the CNS. Both of these effects have been found to play a role in pain and much work has been done to develop therapeutics to enhance the inhibitory effects. Here we will review the dynorphin A compounds that have been designed for the modulation of pain and will discuss where the field stands today. PMID- 26824472 TI - Protozoan Predation of Escherichia coli O157:H7 Is Unaffected by the Carriage of Shiga Toxin-Encoding Bacteriophages. AB - Escherichia coli O157:H7 is a food-borne bacterium that causes hemorrhagic diarrhea and hemolytic uremic syndrome in humans. While cattle are a known source of E. coli O157:H7 exposure resulting in human infection, environmental reservoirs may also be important sources of infection for both cattle and humans. Bacteriophage-encoded Shiga toxins (Stx) carried by E. coli O157:H7 may provide a selective advantage for survival of these bacteria in the environment, possibly through their toxic effects on grazing protozoa. To determine Stx effects on protozoan grazing, we co-cultured Paramecium caudatum, a common ciliate protozoon in cattle water sources, with multiple strains of Shiga-toxigenic E. coli O157:H7 and non-Shiga toxigenic cattle commensal E. coli. Over three days at ambient laboratory temperature, P. caudatum consistently reduced both E. coli O157:H7 and non-Shiga toxigenic E. coli populations by 1-3 log cfu. Furthermore, a wild-type strain of Shiga-toxigenic E. coli O157:H7 (EDL933) and isogenic mutants lacking the A subunit of Stx 2a, the entire Stx 2a-encoding bacteriophage, and/or the entire Stx 1-encoding bacteriophage were grazed with similar efficacy by both P. caudatum and Tetrahymena pyriformis (another ciliate protozoon). Therefore, our data provided no evidence of a protective effect of either Stx or the products of other bacteriophage genes on protozoan predation of E. coli. Further research is necessary to determine if the grazing activity of naturally-occurring protozoa in cattle water troughs can serve to decrease cattle exposure to E. coli O157:H7 and other Shiga-toxigenic E. coli. PMID- 26824471 TI - Impacts of Perinatal Dioxin Exposure on Motor Coordination and Higher Cognitive Development in Vietnamese Preschool Children: A Five-Year Follow-Up. AB - Dioxin concentrations remain elevated in the environment and in humans residing near former US Air Force bases in South Vietnam. Our previous epidemiological studies showed adverse effects of dioxin exposure on neurodevelopment for the first 3 years of life. Subsequently, we extended the follow-up period and investigated the influence of perinatal dioxin exposure on neurodevelopment, including motor coordination and higher cognitive ability, in preschool children. Presently, we investigated 176 children in a hot spot of dioxin contamination who were followed up from birth until 5 years old. Perinatal dioxin exposure levels were estimated by measuring dioxin levels in maternal breast milk. Dioxin toxicity was evaluated using two indices; toxic equivalent (TEQ)-polychlorinated dibenzo-p-dioxins/furans (PCDDs/Fs) and concentration of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). Coordinated movements, including manual dexterity, aiming and catching, and balance, were assessed using the Movement Assessment Battery for Children, Second Edition (Movement ABC-2). Cognitive ability was assessed using the nonverbal index (NVI) of the Kaufman Assessment Battery for Children, Second Edition (KABC-II). In boys, total test and balance scores of Movement ABC-2 were significantly lower in the high TEQ- PCDDs/Fs group compared with the moderate and low exposure groups. NVI scores and the pattern reasoning subscale of the KABC-II indicating planning ability were also significantly lower in the high TCDD exposure group compared with the low exposure group of boys. However, in girls, no significant differences in Movement ABC-2 and KABC-II scores were found among the different TEQ-PCDDs/Fs and TCDD exposure groups. Furthermore, in high risk cases, five boys and one girl highly exposed to TEQ-PCDDs/Fs and TCDD had double the risk for difficulties in both neurodevelopmental skills. These results suggest differential impacts of TEQ PCDDs/Fs and TCDD exposure on motor coordination and higher cognitive ability, respectively. Moreover, high TEQ-PCDDs/Fs exposure combined with high TCDD exposure may increase autistic traits combined with developmental coordination disorder. PMID- 26824473 TI - Cth2 Protein Mediates Early Adaptation of Yeast Cells to Oxidative Stress Conditions. AB - Cth2 is an mRNA-binding protein that participates in remodeling yeast cell metabolism in iron starvation conditions by promoting decay of the targeted molecules, in order to avoid excess iron consumption. This study shows that in the absence of Cth2 immediate upregulation of expression of several of the iron regulon genes (involved in high affinity iron uptake and intracellular iron redistribution) upon oxidative stress by hydroperoxide is more intense than in wild type conditions where Cth2 is present. The oxidative stress provokes a temporary increase in the levels of Cth2 (itself a member of the iron regulon). In such conditions Cth2 molecules accumulate at P bodies-like structures when the constitutive mRNA decay machinery is compromised. In addition, a null Deltacth2 mutant shows defects, in comparison to CTH2 wild type cells, in exit from alpha factor-induced arrest at the G1 stage of the cell cycle when hydroperoxide treatment is applied. The cell cycle defects are rescued in conditions that compromise uptake of external iron into the cytosol. The observations support a role of Cth2 in modulating expression of diverse iron regulon genes, excluding those specifically involved in the reductive branch of the high-affinity transport. This would result in immediate adaptation of the yeast cells to an oxidative stress, by controlling uptake of oxidant-promoting iron cations. PMID- 26824474 TI - Transcriptomic Analysis of Grapevine (cv. Summer Black) Leaf, Using the Illumina Platform. AB - Proceeding to illumina sequencing, determining RNA integrity numbers for poly RNA were separated from each of the four developmental stages of cv. Summer Black leaves by using Illumina HiSeqTM 2000. The sums of 272,941,656 reads were generated from vitis vinifera leaf at four different developmental stages, with more than 27 billion nucleotides of the sequence data. At each growth stage, RNA samples were indexed through unique nucleic acid identifiers and sequenced. KEGG annotation results depicted that the highest number of transcripts in 2,963 (2Avs4A) followed by 1Avs4A (2,920), and 3Avs4A (2,294) out of 15,614 (71%) transcripts were recorded. In comparison, a total of 1,532 transcripts were annotated in GOs, including Cellular component, with the highest number in "Cell part" 251 out of 353 transcripts (71.1%), followed by intracellular organelle 163 out of 353 transcripts (46.2%), while in molecular function and metabolic process 375 out of 525 (71.4%) transcripts, multicellular organism process 40 out of 525 (7.6%) transcripts in biological process were most common in 1Avs2A. While in case of 1Avs3A, cell part 476 out of 662 transcripts (71.9%), and membrane bounded organelle 263 out of 662 transcripts (39.7%) were recorded in Cellular component. In the grapevine transcriptome, during the initial stages of leaf development 1Avs2A showed single transcript was down-regulated and none of them were up-regulated. While in comparison of 1A to 3A showed one up-regulated (photosystem II reaction center protein C) and one down regulated (conserved gene of unknown function) transcripts, during the hormone regulating pathway namely SAUR-like auxin-responsive protein family having 2 up-regulated and 7 down regulated transcripts, phytochrome-associated protein showed 1 up-regulated and 9 down-regulated transcripts, whereas genes associated with the Leucine-rich repeat protein kinase family protein showed 7 up-regulated and 1 down-regulated transcript, meanwhile Auxin Resistant 2 has single up-regulated transcript in second developmental stage, although 3 were down-regulated at lateral growth stages (3A and 4A). In the present study, 489 secondary metabolic pathways related genes were identified during leaf growth, which mainly includes alkaloid (40), anthocyanins (21), Diterpenoid (144), Monoterpenoid (90) and Flavonoids (93). Quantitative real-time PCR was applied to validate 10 differentially expressed transcripts patterns from flower, leaf and fruit metabolic pathways at different growth stages. PMID- 26824475 TI - Tracking Plasticity: Effects of Long-Term Rehearsal in Expert Dancers Encoding Music to Movement. AB - Our knowledge of neural plasticity suggests that neural networks show adaptation to environmental and intrinsic change. In particular, studies investigating the neuroplastic changes associated with learning and practicing motor tasks have shown that practicing such tasks results in an increase in neural activation in several specific brain regions. However, studies comparing experts and non experts suggest that experts employ less neuronal activation than non-experts when performing a familiar motor task. Here, we aimed to determine the long-term changes in neural networks associated with learning a new dance in professional ballet dancers over 34 weeks. Subjects visualized dance movements to music while undergoing fMRI scanning at four time points over 34-weeks. Results demonstrated that initial learning and performance at seven weeks led to increases in activation in cortical regions during visualization compared to the first week. However, at 34 weeks, the cortical networks showed reduced activation compared to week seven. Specifically, motor learning and performance over the 34 weeks showed the typical inverted-U-shaped function of learning. Further, our result demonstrate that learning of a motor sequence of dance movements to music in the real world can be visualized by expert dancers using fMRI and capture highly significant modeled fits of the brain network variance of BOLD signals from early learning to expert level performance. PMID- 26824476 TI - Reduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks. AB - Deletions encompassing the BP1-2 region at 15q11.2 increase schizophrenia and epilepsy risk, but only some carriers have either disorder. To investigate the role of CYFIP1, a gene within the region, we performed knockdown experiments in human neural progenitors derived from donors with 2 copies of each gene at the BP1-2 locus. RNA-seq and cellular assays determined that knockdown of CYFIP1 compromised cytoskeletal remodeling. FMRP targets and postsynaptic density genes, each implicated in schizophrenia, were significantly overrepresented among differentially expressed genes (DEGs). Schizophrenia and/or epilepsy genes, but not those associated with randomly selected disorders, were likewise significantly overrepresented. Mirroring the variable expressivity seen in deletion carriers, marked between-line differences were observed for dysregulation of disease genes. Finally, a subset of DEGs showed a striking similarity to known epilepsy genes and represents novel disease candidates. Results support a role for CYFIP1 in disease and demonstrate that disease-related biological signatures are apparent prior to neuronal differentiation. PMID- 26824477 TI - Hepatic Macrosteatosis Is Partially Converted to Microsteatosis by Melatonin Supplementation in ob/ob Mice Non-Alcoholic Fatty Liver Disease. AB - BACKGROUND: Obesity is a common risk factor for non-alcoholic fatty liver disease (NAFLD). Currently, there are no specific treatments against NAFLD. Thus, examining any molecule with potential benefits against this condition emerged melatonin as a molecule that influences metabolic dysfunctions. The aim of this study was to determine whether melatonin would function against NAFDL, studying morphological, ultrastuctural and metabolic markers that characterize the liver of ob/ob mice. METHODS: Lean and ob/ob mice were supplemented with melatonin in the drinking water for 8 weeks. Histology and stereology were performed to assess hepatic steatosis and glycogen deposition. Ultrastructural features of mitochondria, endoplasmic reticulum (ER) and their juxtapositions were evaluated in livers of all experimental groups. Furthermore, hepatic distribution and expression of markers of ER and mitochondria (calnexin, ATP sintase beta, GRP78 and CHOP) and metabolic dysfunction (RPB4, beta-catenin) and cellular longevity (SIRT1) were analyzed. RESULTS: Melatonin significantly reduced glycemia, identified also by a decrease of hepatic RBP4 expression, reversed macrosteatosis in microsteatosis at the hepatic pericentral zone, enlarged ER-mitochondrial distance and ameliorated the morphology and organization of these organelles in ob/ob mouse liver. Furthermore, in ob/ob mice, calnexin and ATP synthase beta were partially restored, GRP78 and CHOP decreased in periportal and midzonal hepatocytes and beta-catenin expression was, in part, restored in peripheral membranes of hepatocytes. Melatonin supplementation to ob/ob mice improves hepatic morphological, ultrastructural and metabolic damage that occurs as a result of NAFLD. CONCLUSIONS: Melatonin may be a potential adjuvant treatment to limit NAFLD and its progression into irreversible complications. PMID- 26824478 TI - The Early-Acting Peroxin PEX19 Is Redundantly Encoded, Farnesylated, and Essential for Viability in Arabidopsis thaliana. AB - Peroxisomes are single-membrane bound organelles that are essential for normal development in plants and animals. In mammals and yeast, the peroxin (PEX) proteins PEX3 and PEX19 facilitate the early steps of peroxisome membrane protein (PMP) insertion and pre-peroxisome budding from the endoplasmic reticulum. The PEX3 membrane protein acts as a docking site for PEX19, a cytosolic chaperone for PMPs that delivers PMPs to the endoplasmic reticulum or peroxisomal membrane. PEX19 is farnesylated in yeast and mammals, and we used immunoblotting with prenylation mutants to show that PEX19 also is fully farnesylated in wild-type Arabidopsis thaliana plants. We examined insertional alleles disrupting either of the two Arabidopsis PEX19 isoforms, PEX19A or PEX19B, and detected similar levels of PEX19 protein in the pex19a-1 mutant and wild type; however, PEX19 protein was nearly undetectable in the pex19b-1 mutant. Despite the reduction in PEX19 levels in pex19b-1, both pex19a-1 and pex19b-1 single mutants lacked notable peroxisomal beta-oxidation defects and displayed normal levels and localization of peroxisomal matrix and membrane proteins. The pex19a-1 pex19b-1 double mutant was embryo lethal, indicating a redundantly encoded critical role for PEX19 during embryogenesis. Expressing YFP-tagged versions of either PEX19 isoform rescued this lethality, confirming that PEX19A and PEX19B act redundantly in Arabidopsis. We observed that pex19b-1 enhanced peroxisome-related defects of a subset of peroxin-defective mutants, supporting a role for PEX19 in peroxisome function. Together, our data indicate that Arabidopsis PEX19 promotes peroxisome function and is essential for viability. PMID- 26824479 TI - Stimulation of Nitric Oxide Production Contributes to the Antithrombotic Effect of Stromal Cell-Derived Factor-1alpha in Preventing Microsurgical Anastomotic Thrombosis. AB - Background Intimal injury plays a critical role in initiating the pathogenesis of thrombosis formation after microsurgical anastomosis. Application of stromal cell derived factor-1alpha (SDF-1alpha) is reported to promote early regeneration of injured intima through migration of endothelial cells and mobilization of endothelial progenitor cells. We therefore hypothesized that local transfer of SDF-1alpha gene would inhibit microsurgical anastomotic thrombosis. Methods Sixty Sprague-Dawley rats were used and divided randomly into three groups (SDF-1alpha group, plasmid group, and saline group) in this study. Plasmid DNA encoding SDF 1alpha, empty plasmid, and saline were injected into the left femoral muscles of rats from each group, respectively. Seven days after injection, peripheral blood samples were obtained to measure the plasma levels of SDF-1alpha and nitric oxide (NO). The left femoral artery of each rat was crushed, transected, and repaired by end-to-end microsurgical anastomosis. Vascular patency was assessed at 15, 30, and 120 minutes after reperfusion using milk test. Thrombosis formation was assessed with hematoxylin and eosin staining and scanning electron microscopy at 120 minutes postoperatively. Results The plasma levels of SDF-1alpha and NO in SDF-1alpha group were significantly higher than those in plasmid group and saline group (p < 0.01). The patency rate in SDF-1alpha group was significantly higher than that in control groups at 120 minutes after reperfusion (p < 0.05). Treatment of SDF-1alpha significantly reduced the size of thrombotic occlusion when compared with controls (p < 0.05). All SDF-1alpha recipients exhibited decreased thrombosis under scanning electron microscopy. Conclusions The current study demonstrated that local transfer of SDF-1alpha gene increases arterial patency and inhibits microsurgical anastomotic thrombosis in a crush model of femoral artery in rat. The antithrombotic effect of SDF-1alpha may be mediated through increased production of endogenous NO. These findings provide a novel approach for inhibition of microsurgical anastomotic thrombosis. PMID- 26824480 TI - Interactions between mefloquine and the anti-fibrotic drug silymarin on Schistosoma mansoni infections in mice. AB - The present study tests the anti-inflammatory and anti-fibrotic effects of silymarin alone or combined with mefloquine on acute schistosomiasis by evaluating parasitological, histopathological, biochemical and immunological parameters. Male CDI Swiss mice were divided into seven groups, which included healthy controls, mice infected with Schistosoma mansoni or treated with silymarin (140 mg/kg body weight) or mefloquine (400 mg/kg body weight), or mice treated with a combination of both drugs and uninfected mice simply treated with mefloquine or silymarin alone. All mouse groups were sacrificed 8 weeks post infection (pi) and/or post-treatment. Those infected mice treated with both silymarin and mefloquine showed a significant decrease (P < 0.001) in worm burden, immunoglobulins (IgG and IgM), liver function enzymes and granuloma diameter, with complete eradication of immature and mature eggs. In conclusion, treatment with silymarin combined with mefloquine in murine schistosomiasis was able to reduce granulomatous reactions and hepatic fibrosis. Hence, this combination is a new strategy to be studied as an efficient tool in the treatment of schistosomal liver fibrosis. PMID- 26824481 TI - Correction: Hyaluronic Acid Injections Are Associated with Delay of Total Knee Replacement Surgery in Patients with Knee Osteoarthritis: Evidence from a Large U.S. Health Claims Database. PMID- 26824482 TI - Palladium-Catalyzed Modular Synthesis of Substituted Piperazines and Related Nitrogen Heterocycles. AB - We report here a novel method for the modular synthesis of highly substituted piperazines and related bis-nitrogen heterocycles via a palladium-catalyzed cyclization reaction. The process couples two of the carbons of a propargyl unit with various diamine components to provide nitrogen heterocycles in generally good to excellent yields and high regio- and stereochemical control. PMID- 26824483 TI - A simple and highly sensitive assay of perfluorooctanoic acid based on resonance light scattering technique. AB - A simple, highly sensitive resonance light scattering (RLS) method for the detection of perfluorooctanoic acid (PFOA) has been developed based on the interaction with crystal violet (CV). It was found that PFOA can form complexes with CV in acid medium resulting in remarkable enhancement of the RLS intensity of the system. And the enhanced RLS intensities are in proportion to the concentration of PFOA in the range of 0.1-25.0 MUmol/L (R(2)=0.9998), with a detection limit of 11.0 nmol/L (S/N=3). In this work, the optimum reaction conditions and the interferences of foreign substances were investigated. The reaction mechanism between CV and PFOA was also studied by the absorption spectrum and scanning electron microscope (SEM). This method is successfully applied to the determination of PFOA in tap water and Jialing river water samples with RSD<=4.04%. PMID- 26824484 TI - Stability-indicating spectrophotometric methods for determination of the anticoagulant drug apixaban in the presence of its hydrolytic degradation product. AB - Apixaban (a novel anticoagulant agent) was subjected to a stress stability study including acid, alkali, oxidative, photolytic, and thermal degradation. The drug was found to be only liable to acidic and alkaline hydrolysis. The degradation product was then isolated and identified by IR and GC-mass spectrometry. Four spectrophotometric methods, namely; first derivative (D(1)), derivative ratio (DR), ratio difference (RD) and mean centering of ratio spectra (MCR), have been suggested for the determination of apixaban in presence of its hydrolytic degradation product. The proposed methods do not require any preliminary separation step. The accuracy, precision and linearity ranges of the proposed methods were determined, and the methods were validated as per ICH guidelines and the specificity was assessed by analyzing synthetic mixtures containing different percentages of the degradation product with the drug. The developed methods were successfully applied for the determination of apixaban in bulk powder and its tablet dosage form. PMID- 26824485 TI - Uric Acid-Induced Inflammation Is Mediated by the Parathyroid Hormone:25 Hydroxyvitamin D Ratio in Obese Adolescents. AB - BACKGROUND: Elevated serum uric acid (SUA) level is strongly associated with prevalence of metabolic syndrome (MS), elevated parathyroid hormone (PTH) levels, and 25-hydroxyvitamin D [25(OH)D] insufficiency in adults. We examined the relationship among SUA, [25(OH)D], PTH, and inflammation in obese adolescents, in obese adolescents with and without MS. METHODS: Body mass index, body composition, 25(OH)D, PTH, fasting lipids, glucose, high-sensitivity C-reactive protein (hs-CRP), SUA, hemoglobin A1c (HbA1c), insulin, and the homeostatic model assessment of insulin resistance (HOMA-IR) were evaluated in 152 obese adolescents. RESULTS: Hyperuricemia [SUA >= 6.0 mg/dL (357 MUM)] was present in 54.6% of entire cohort without significant ethnic/racial differences. While SUA was negatively correlated with high-density lipoprotein cholesterol (HDL-C) and 25(OH)D (P < 0.01), it was positively correlated with fat mass (FM), PTH, PTH:25(OH)D, and hs-CRP (P < 0.01). Vitamin D deficiency [25(OH)D <50 nM] was present in 47.4% of subjects, and PTH and 25(OH)D were inversely correlated (P < 0.0001). FM was negatively correlated with 25(OH)D (r = -0.29; P < 0.001), but was positively correlated with PTH (P < 0.0001). MS was identified in 53.3% of cohort with higher FM, SUA, hs-CRP, HOMA-IR, PTH, and PTH:25(OH)D ratio than the non-MS subgroup (P < 0.001) with similar 25(OH)D status. Multiple regression analysis showed that the PTH:25(OH)D ratio mediated the relationship between SUA and hs-CRP (beta = 0.19, P < 0.05 to beta = 0.15, P = 0.19). CONCLUSIONS: Hyperuricemia is strongly associated with PTH and hs-CRP levels independent of vitamin D status. The relationship between SUA and low-grade inflammation is mediated by the PTH:25(OH)D ratio in obese adolescents. PMID- 26824487 TI - Reversible Carbon Dioxide Binding by Simple Lewis Base Adducts with Electron-Rich Phosphines. AB - For the efficient utilization of carbon dioxide as feedstock in chemical synthesis, low-energy-barrier CO2 activation is a valuable tool. We report a metal-free approach to reversible CO2 binding under mild conditions based on simple Lewis base adducts with electron-rich phosphines. Variable-temperature NMR studies and DFT calculations reveal almost thermoneutral CO2 binding with low energy barriers or stable CO2 adduct formation depending on the phosphines donor ability. The most basic phosphine forms an air-stable CO2 adduct that was used as phosphine transfer agent, providing a convenient access to transition-metal complexes with highly electron-rich phosphine ligands relevant to catalysis. PMID- 26824486 TI - A novel mutation in PAX3 associated with Waardenburg syndrome type I in a Chinese family. AB - CONCLUSION: The novel compound heterozygous mutation in PAX3 was the key genetic reason for WS1 in this family, which was useful to the molecular diagnosis of WS1. PURPOSE: Screening the pathogenic mutations in a four generation Chinese family with Waardenburg syndrome type I (WS1). METHODS: WS1 was diagnosed in a 4 year-old boy according to the Waardenburg syndrome Consortium criteria. The detailed family history revealed four affected members in the family. Routine clinical, audiological examination, and ophthalmologic evaluation were performed on four affected and 10 healthy members in this family. The genetic analysis was conducted, including the targeted next-generation sequencing of 127 known deafness genes combined with Sanger sequencing, TA clone and bioinformatic analysis. RESULTS: A novel compound heterozygous mutation c.[169_170insC;172_174delAAG] (p.His57ProfsX55) was identified in PAX3, which was co-segregated with WS1 in the Chinese family. This mutation was absent in the unaffected family members and 200 ethnicity-matched controls. The phylogenetic analysis and three-dimensional (3D) modeling of Pax3 protein further confirmed that the novel compound heterozygous mutation was pathogenic. PMID- 26824488 TI - Environmental Malpractice. PMID- 26824489 TI - Method development and survey of Sudan I-IV in palm oil and chilli spices in the Washington, DC, area. AB - Sudan I, II, III and IV dyes are banned for use as food colorants in the United States and European Union because they are toxic and carcinogenic. These dyes have been illegally used as food additives in products such as chilli spices and palm oil to enhance their red colour. From 2003 to 2005, the European Union made a series of decisions requiring chilli spices and palm oil imported to the European Union to contain analytical reports declaring them free of Sudan I-IV. In order for the USFDA to investigate the adulteration of palm oil and chilli spices with unapproved colour additives in the United States, a method was developed for the extraction and analysis of Sudan dyes in palm oil, and previous methods were validated for Sudan dyes in chilli spices. Both LC-DAD and LC-MS/MS methods were examined for their limitations and effectiveness in identifying adulterated samples. Method validation was performed for both chilli spices and palm oil by spiking samples known to be free of Sudan dyes at concentrations close to the limit of detection. Reproducibility, matrix effects, and selectivity of the method were also investigated. Additionally, for the first time a survey of palm oil and chilli spices was performed in the United States, specifically in the Washington, DC, area. Illegal dyes, primarily Sudan IV, were detected in palm oil at concentrations from 150 to 24 000 ng ml(-1). Low concentrations (< 21 ug kg(-1)) of Sudan dyes were found in 11 out of 57 spices and are most likely a result of cross-contamination during preparation and storage and not intentional adulteration. PMID- 26824490 TI - Kosterlitz-Thouless physics: a review of key issues. AB - This article reviews, from a very personal point of view, the origins and the early work on transitions driven by topological defects such as vortices in the two dimensional planar rotor model and in (4)Helium films and dislocations and disclinations in 2D crystals. I cover the early papers with David Thouless and describe the important insights but also the errors and oversights since corrected by other workers. I then describe some of the experimental verifications of the theory and some numerical simulations. Finally applications to superconducting arrays of Josephson junctions and to recent cold atom experiments are described. PMID- 26824491 TI - Isomerization and Oxidation in the Complementarity-Determining Regions of a Monoclonal Antibody: A Study of the Modification-Structure-Function Correlations by Hydrogen-Deuterium Exchange Mass Spectrometry. AB - Chemical modifications can potentially change monoclonal antibody's (mAb) local or global conformation and therefore impact their efficacy as therapeutic drugs. Modifications in the complementarity-determining regions (CDRs) are especially important because they can impair the binding affinity of an antibody for its target and therefore drug potency as a result. In order to understand the impact on mAb attributes induced by specific chemical modifications within the CDR, hydrogen-deuterium exchange mass spectrometry (HDX MS) was used to interrogate the conformational impact of Asp isomerization and Met oxidation in the CDRs of a model monoclonal antibody (mAb1). Our results indicate that despite their proximity to each other, Asp54 isomerization and Met56 oxidation in CDR2 in the heavy chain of mAb1 result in opposing conformational impacts on the local and nearby regions, leading directly to different alterations on antibody-antigen binding affinity. This study revealed direct evidence of local and global conformational changes caused by two of the most common degradation pathways in the CDRs of a mAb and identified correlations between chemical modification, structure, and function of the therapeutic monoclonal antibody. PMID- 26824492 TI - TNFalpha up-regulates COX-2 in chronic progressive nephropathy through nuclear accumulation of RelB and NF-kappaB2. AB - OBJECTIVE: The pathogenesis of progressive nephropathies involves inflammatory factors. The inhibition of cyclooxygenase-2 (COX-2) can limit renal damage and inflammation. However, the mechanism of up-regulation of COX-2 in nephropathy is poorly defined. MATERIALS AND METHODS: Here we found that tumor necrosis factor alpha (TNFalpha) was involved in expression of COX-2 in normal rat kidney (NRK) cell line. RESULTS: TNFalpha stimulated COX-2 production in a time-dependent manner in NRK cells by inducing nuclear accumulation of RelB and nuclear factor kappa B2 (NF-kappaB2) and their association with COX-2 gene promoter. Depletion of IkappaB-inducing kinase alpha, a positive regulator of activation of p100 processing to active p52, attenuated TNFalpha-induced COX-2 production. Furthermore, TNFalpha induced COX-2 production and nuclear import in anti thymocyte serum (ATS) nephropathy. DISCUSSION AND CONCLUSION: These data suggest that TNFalpha-RelB/p52 pathway may be involved in the early stages of renal damage, in part by stimulating COX-2 and inflammatory responses. PMID- 26824493 TI - Bone Samples Extracted from Embalmed Subjects Are Not Appropriate for the Assessment of Bone Quality at the Molecular Level Using Raman Spectroscopy. AB - Bone samples extracted from embalmed cadavers are commonly used as controls in the study of bone. The effects of embalmment on the molecular composition of bone are unknown. The objective of this study was to determine the effect of embalmment on the molecular composition and structure of bone, as evaluated by Raman spectroscopy. Bone samples of femoral heads from five embalmed donors and five fresh-frozen donors were compared using Raman microspectroscopy with DuoScan technology. Physicochemical parameters simultaneously describing the organic and mineral phases of bone were compared using the Mann-Whitney U test. Partial least squares discriminant analysis (PLS-DA) was used to determine specific Raman spectral features of each group. Study of the mineral phase showed a 15% reduction of the mineral-to-matrix ratio (p < 0.001), an 8% decrease of type B carbonate substitution (p < 0.001), and a 2% increase in crystallinity (p < 0.001) in the embalmed donors group compared to those of the fresh donors group. Regarding the organic phase of bone, the hydroxyproline-to-proline ratio was increased by 18% in the embalmed group (p < 0.001), with no variation in both the relative proteoglycan content (GAG/CH3) (p = 0.08) and collagen maturity (p = 0.57). PLS-DA showed that the embalmed group was characterized mainly by peaks assigned to hydroxyproline, lipids, and collagen. Embalmment induces significant modifications of the molecular composition of bone. Bone samples from embalmed subjects should be avoided as controls for Raman spectroscopy studies. Preservation procedures performed prior to bone sampling should be reported in studies using human cadaver samples. PMID- 26824494 TI - Eric Davidson. A genomic control odyssey. PMID- 26824495 TI - Eric Davidson's career as a paleontologist. PMID- 26824496 TI - Ramblin' and resonating with Eric- an unlikely but enduring bond. PMID- 26824497 TI - Knob creek and the mountainous landscape of Eric Davidson. PMID- 26824498 TI - Eric Davidson was a former student of mine. PMID- 26824499 TI - In memory of Eric H. Davidson. PMID- 26824502 TI - Dosing de novo combinations of two targeted drugs: Towards a customized precision medicine approach to advanced cancers. AB - Metastatic cancers harbor complex genomic alterations. Thus, monotherapies are often suboptimal. Individualized combinations are needed in order to attenuate resistance. To help inform selection of safe starting doses for novel, two-agent, targeted drug combinations, we identified clinical trials in adult oncology patients who received targeted drug doublets (PubMed, January 1, 2010 through December 31, 2013). The dose percentage was calculated for each drug: (safe dose in combination divided by single agent full dose) X 100. Additive dose percentage represented the sum of the dose percentage for each drug. A total of 144 studies (N = 8568 patients; 95 combinations) were analyzed. In 51% of trials, each of the two drugs could be administered at 100% of their full dose. The lowest safe additive dose percentage was 60% if targets and/or class of drugs overlapped, or in the presence of mTor inhibitors, which sometimes compromised the combination dose. If neither class nor target overlapped and if mTor inhibitors were absent, the lowest safe additive dose percentage was 143%. The current observations contribute to the knowledge base that informs safe starting doses for new combinations of targeted drugs in the context of clinical trials or practice, hence facilitating customized combination therapies. PMID- 26824501 TI - SIRT1 increases YAP- and MKK3-dependent p38 phosphorylation in mouse liver and human hepatocellular carcinoma. AB - Both oncoprotein and tumor-suppressor activity have been reported for SIRTUIN1 (SIRT1) and p38 in many types of cancer. The effect of SIRT1 on p38 phosphorylation (p-p38) remains controversial and may be organ- and cell specific. We found that SIRT1 is essential for maintaining liver size and weight in mice. SIRT1 levels were elevated in human HCC compared to adjacent normal liver tissue, and its expression correlated positively with p-p38 levels. Additionally, SIRT1-activated p38 increased liver cancer malignancy. SIRT1 increased phosphorylation and nuclear accumulation of p38, possibly by increasing MKK3 expression. SIRT1 also induced YAP expression, which in turn increased MKK3 transcription. Positive correlations between SIRT1, YAP, MKK3, and p-p38 levels indicate that blocking their activity may prove helpful in treating HCC. PMID- 26824500 TI - HBV polymerase overexpression due to large core gene deletion enhances hepatoma cell growth by binding inhibition of microRNA-100. AB - Different types of hepatitis B virus (HBV) core gene deletion mutants were identified in chronic hepatitis B patients. However, their clinical roles in different stages of natural chronic HBV infection remained unclear. To address this issue, HBV core genes were sequenced in three gender- and age-matched patient groups diagnosed as chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC), respectively. Functional analysis of the identified mutants was performed. A novel type of large-fragment core gene deletion (LFCD) was identified exclusively in HCC patients and significantly associated with unfavorable postoperative survival. The presence of LFCDs resulted in generation of precore-polymerase fusion protein or brought the polymerase reading frame under direct control of HBV precore/core promoter, leading to its over expression. Enhanced cell proliferation and increased tumorigenicity in nude mice were found in hepatoma cells expressing LFCDs. Because of the epsilon-binding ability of HBV polymerase, we hypothesized that the over-expressed polymerase carrying aberrant amino-terminal sequence could bind to cellular microRNAs. Screening of a panel of microRNAs revealed physical association of a precore polymerase fusion protein with microRNA-100. A binding inhibition effect on microRNA-100 by the precore-polymerase fusion protein with up-regulation of its target, polo-like kinase 1 (PLK1), was discovered. The binding inhibition and growth promoting effects could be reversed by overexpressing microRNA-100. Together, HCC patients carrying hepatitis B large-fragment core gene deletion mutants had an unfavorable postoperative prognosis. The growth promoting effect was partly due to polymerase overexpression, leading to binding inhibition of microRNA-100 and up-regulation of PLK1. PMID- 26824503 TI - Residual tumor micro-foci and overwhelming regulatory T lymphocyte infiltration are the causes of bladder cancer recurrence. AB - Bladder cancer has an unexplained, high recurrence rate. Causes of recurrence might include the presence of sporadic tumor micro-foci in the residual urothelial tissue after surgery associated with an inverted ratio between intratumoral effector and regulatory T cell subsets. Hence, surgical specimens of both tumors and autologous, macroscopically/histologically free-of-tumor tissues were collected from 28 and 20 patients affected by bladder or renal cancer, respectively. The frequencies of effector (IFNgamma+ and IL17+ T cells) and regulatory (CD4+CD25hiCD127lo and CD8+CD28-CD127loCD39+ Treg) T cell subpopulations among tumor infiltrating lymphocytes were analyzed by immunofluorescence, while the gene expression of MAGE-A1 and MAGE-A2 tumor associated antigens was studied by RT-PCR. The results show that both the T cell infiltrate and the frequency of MAGE-A1/A2 gene expression were comparable in tumors and in autologous free-of-tumor tissues in bladder cancer, while the autologous free-of-tumor renal tissues showed reduced T cell infiltrate and frequency of MAGE gene expression as compared to the autologous tumors. Importantly, the intra-tumor T effector/Treg cell ratio was consistently <1 in bladder cancer patients (n. 7) who relapsed within two years, while it was always >1 in patients (n. 6) without recurrence (regardless of tumor stage) (P = 0.0006, Odds ratio = 195). These unprecedented findings clarify the pathogenic mechanism of bladder cancer recurrence and suggest that microscopically undetectable micro foci of tumor may predispose to recurrence when associated with an inverted intratumoral T effector/Treg cell ratio. PMID- 26824505 TI - Alternatives to surgery for the treatment of myomas. AB - Uterine fibroids are benign neoplasms that can cause distressing symptoms in women during their reproductive age. They are often associated with menorrhagia that can determine anemia or bulk-related symptoms. Different treatment options are available: medical therapy has the goal to treat related symptoms, while semi invasive or non-invasive uterus-sparing procedures aim to treat symptoms and eventually to determine a reduction in fibroids size. In this review we illustrate the current semi-invasive and totally non-invasive most frequently used uterus sparing procedures available. A review of the literature along with personal experience will offer the readers a panoramic view of these up-to-date treatments to be considered as different possibilities to treat women affected by uterine fibroids looking for uterus conserving non-surgical approach. PMID- 26824504 TI - Alcohol-related injuries, hazardous drinking, and BrAC levels among a sample of bar patrons. AB - BACKGROUND: Alcohol-related injuries are a serious public health issue and research has found that alcohol consumption is positively correlated with injury risk. OBJECTIVE: To better understand the association between alcohol consumption and injury risk. METHODS: We conducted four anonymous cross-sectional field studies among a sample of bar patrons (N = 917) to assess breath alcohol concentration (BrAC) levels, hazardous drinking levels (based on AUDIT-C score), and past year alcohol-related injuries in Fall 2014. Next, we conducted two logistic regression analyses to predict alcohol-related injuries: one model used hazardous drinking level as a predictor variable and the other model used BrAC. RESULTS: Among participants in our sample, the average BrAC% was .076 (SD =.055) and the average hazardous drinking score (based on the AUDIT-C) was 5.0 (SD = 2.6). The majority of participants indicated that they had not experienced an alcohol-related injury in the past year (859; 93.7%). Our regression analyses found that each incremental increase in a participants' hazardous drinking score increased the odds of experiencing a self-reported alcohol-related injury by 1.4 times and as BrAC increased one unit of change (percentage), the odds of a past year alcohol related injury increased twofold (OR = 2.2). Other covariates (ie, age, gender, race, college student status) did not significantly predict alcohol related injuries in either model. DISCUSSION AND CONCLUSIONS: High-risk drinking behaviors, including higher BrAC levels, greatly influenced experiencing an alcohol-related injury. SCIENTIFIC SIGNIFICANCE: This is the first examination of BrAC levels and alcohol-related injuries in a primarily college student sample. PMID- 26824506 TI - Leiomyomas and infertility. AB - Leiomyomas are the commonest benign tumor in the female reproductive tract. Even though their role on infertility is still questionable, evidence to date suggest that the anatomic location may be related to reproductive outcomes. Several possible mechanisms suggest that leiomyomas may affect fertility, especially in terms of the anatomical distortion of endometrial cavity, the abnormal uterine contractility, reduced blood supply to the endometrium and altered endometrial receptivity. The effect of leiomyomas on IVF outcomes has been the subject of many studies; however, a definitive direction is yet required to adjust clinical management accordingly. Management of leiomyomas is challenging in terms of clinical decision, especially among subfertile patients, since potential treatment complications and their consequences in endometrial dynamics should be also accounted. Expectant management is recommended for asymptomatic patients, whereas in symptomatic subfertile patients, medical and/ or surgical management is usually recommended. PMID- 26824507 TI - Leiomyomas and genomics. AB - Uterine leiomyomas represent a major health problem for women in reproductive age, as these benign monoclonal tumors introduce a pathological state in the female reproductive system structure and function. Despite their common clinical occurrence, the etiology of their incidence remains unclear. Several theories have been proposed in an attempt to clarify the etiology and route of tumor formation in leiomyomas, with estrogen/progesterone and several growth factors, cytokines, chemokines, genes and microRNAs to have been implied as key regulators in their growth. The structured theories presented so far indicate multiple candidates or an occurring interplay between these factors, with the reported findings to denote a composite molecular and biological involvement to attribute to the nature of their pathogenesis. Undoubtedly the evolving molecular technologies and recent developments allow a faster assembly of a vast array of data that should ultimately contribute in the establishment of the etiology and the related events leading to leiomyoma formation to ensure a more targeted management and treatment of the affected individuals. PMID- 26824508 TI - Control-matched surgical evaluation of endometriosis progression after IVF: a retrospective cohort study. AB - BACKGROUND: The aim of this study was to examine the surgical findings at repeated surgeries for endometriosis and to compare disease progression in patients after IVF to those without interval fertility treatments. METHODS: A retrospective case-control study set at the referral center for gynecologic endoscopy at Stanford University. Women who had two surgeries for treatment of symptomatic endometriosis since 1997 were searched in the database. Twenty-one women were identified who underwent IVF treatment between the two procedures (IVF group), and compared to 36 women who did not receive any fertility treatment (controls). The main outcomes were time to recurrence and surgical findings including rASRM score. The presence and size of endometrioma, rectovaginal and para-rectal spaces location of endometriosis were also compared between the two surgical procedures. RESULTS: Demographics in the two groups were similar. The change in rASRM score between surgeries was not significantly different (P=0.80) between the two groups. There was no difference between the two groups in the size and number of pathology proven endometriomas as well as no difference in the presence of rectovaginal and pararectal endometriosis. CONCLUSIONS: No significant difference was found in the two groups, suggesting that IVF treatment does not lead to an accelerated progression of endometriosis in patients with recurrence. PMID- 26824509 TI - Mapping regions in Ste5 that support Msn5-dependent and -independent nuclear export. AB - Careful control of the available pool of the MAPK scaffold Ste5 is important for mating-pathway activation and the prevention of inappropriate mating differentiation in haploid Saccharomyces cerevisiae. Ste5 shuttles constitutively through the nucleus, where it is degraded by a ubiquitin-dependent mechanism triggered by G1 CDK phosphorylation. Here we narrow-down regions of Ste5 that mediate nuclear export. Four regions in Ste5 relocalize SV40-TAgNLS-GFP-GFP from nucleus to cytoplasm. One region is N-terminal, dependent on exportin Msn5/Ste21/Kap142, and interacts with Msn5 in 2 hybrid assays independently of mating pheromone, Fus3, Kss1, Ptc1, the NLS/PM, and RING-H2. A second region overlaps the PH domain and Ste11 binding site and 2 others are on the vWA domain and include residues essential for MAPK activation. We find no evidence for dependence on Crm1/Xpo1, despite numerous potential nuclear export sequences (NESs) detected by LocNES and NetNES1.1 predictors. Thus, Msn5 (homolog of human Exportin-5) and one or more exportins or adaptor molecules besides Crm1/Xpo1 may regulate Ste5 through multiple recognition sites. PMID- 26824510 TI - Effect of vitamin D supplementation on measures of arterial stiffness: a systematic review and meta-analysis of randomized controlled trials. AB - BACKGROUND: Low vitamin D has been associated with poor arterial compliance in observational studies. Arterial stiffness has prognostic value for cardiovascular disease risk. The aim of this systematic review was to clarify the literature surrounding the use of vitamin D to ameliorate arterial stiffness. METHODS: We conducted a systematic review of the MEDLINE, Scopus and EMBASE databases for randomized controlled clinical trials investigating the effect of vitamin D supplementation on pulse wave velocity (PWV) and/or augmentation index (AI) as indicators of arterial stiffness. We meta-analysed data and calculated standardized mean difference (SMD) and 95% confidence intervals (CI) using inverse-variance models on RevMan v5.3 software. Study quality was assessed using a modified Jadad scale. RESULTS: A total of 607 unique records were identified, of which 18 satisfied our inclusion and exclusion criteria. Study quality was high, ranging from 9 to 12 (of 13). Study design in terms of vitamin D dosing protocol (range: 1000-5700 IU/day), follow-up times (range: 1-12 months), sample size (range: n = 29-183) and recruitment strategies varied markedly. Thirteen studies had data for meta-analysis. Vitamin D was associated with nonsignificant reductions in PWV [SMD = -0.10; 95% CI: -0.24, 0.04; P = 0.17; n = 806 from ten studies] and AI [-0.15; -0.32, 0.02; 0.08; n = 551 from eight studies]. DISCUSSION: There is inconsistent evidence to suggest that vitamin D supplementation improves indicators of arterial stiffness. This may be attributable to the heterogeneity in study design. Therefore, large and well designed randomized studies are required to determine the casual relationships between vitamin D and arterial stiffness and cardiovascular risk. PMID- 26824511 TI - In Situ Photocatalytic Synthesis of Ag Nanoparticles (nAg) by Crumpled Graphene Oxide Composite Membranes for Filtration and Disinfection Applications. AB - Graphene oxide (GO) materials have demonstrated considerable potential in next generation water treatment membrane-based technologies, which include antimicrobial applications. GO antimicrobial properties can be further enhanced by preloading or chemically generating surface-associated nanoscale silver particles (nAg). However, for these systems, enhanced antimicrobial functionality decreases over time as a function of Ag mass loss via dissolution (as Ag(+)). In this work, we demonstrate facile photocatalytic in situ synthesis of nAg particles by crumpled GO-TiO2 (GOTI) nanocomposites as an approach to (re)generate, and thus maintain, enhanced antimicrobial activity over extended operation times. The described photocatalytic formation process is highly efficient and relatively fast, producing nAg particles over a size range of 40 to 120 nm and with active (111) planes. Additionally, we show in situ surface-based photocatalyzed synthesis of nAg particles at the surface of GOTI nanocomposite membrane assemblies, allowing for simultaneous filtration and disinfection. With ca. 3 log inactivation for both Escherichia coli and Bacillus subtilis, the described membrane assemblies with in situ formed nAg demonstrate enhanced antimicrobial activity compared to the GOTI membrane surface or the support membrane alone. Under typical conditions, the working and operational time (Ag dissolution time) is calculated to be over 2 orders of magnitude higher than the loading (synthesis) time (e.g., 123 h versus 0.5 h, respectively). Taken together, results highlight the described material-based process as a potentially novel antifouling membrane technology. PMID- 26824513 TI - Tracheobronchial Branching Abnormalities: Lobe-based Classification Scheme. AB - Boyden's nomenclature, which was based on postmortem specimens and published in 1955 prior to the advent of computed tomography (CT), is commonly used to describe the normal segmental bronchial anatomy and various abnormalities. However, several additional anomalies have been recognized since that time, and there is some confusion over the names used to describe these anomalies. Several congenital branching anomalies affecting the trachea, main bronchi, and intermediate bronchus have been reported, all of which can be recognized at chest CT but are often overlooked. These anomalies, which probably occur early in fetal life, can be either supernumerary, with defects occurring at 29-30 days gestation, or displaced, with defects occurring later. Tracheobronchial positional anomalies are often associated with other congenital abnormalities but may be isolated. They often are asymptomatic but can be responsible for pulmonary symptoms such as dyspnea, recurrent pneumonia, and hemoptysis. It is essential that these anomalies are recognized prior to lung resection to avoid complications, especially when video-assisted thoracoscopic surgery is performed. In addition, bronchoscopists should be aware of these anomalies before performing diagnostic or therapeutic bronchoscopic procedures. Awareness of a few key bronchial anatomic principles and use of a lobe-based classification scheme will facilitate recognition of tracheobronchial positional anomalies. PMID- 26824512 TI - "Biliary Diseases with Pancreatic Counterparts": Cross-sectional Imaging Findings. AB - On the basis of the similarities in the histopathologic findings and the clinical biologic behaviors of select biliary and pancreatic conditions, a new disease concept, "biliary diseases with pancreatic counterparts," has been proposed. Both nonneoplastic and neoplastic pathologic conditions of the biliary tract have their counterparts in the pancreas. Immunoglobulin G4 (IgG4)-related sclerosing cholangitis is the biliary manifestation of IgG4-related sclerosing disease, and type 1 autoimmune pancreatitis is its pancreatic counterpart. People with chronic alcoholism can develop peribiliary cysts and fibrosis as well as pancreatic fibrosis and chronic pancreatitis simultaneously. Pancreatic ductal adenocarcinoma, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm are considered pancreatic counterparts for the biliary neoplasms of extrahepatic cholangiocarcinoma, intraductal papillary neoplasm of the biliary tract, and hepatic mucinous cystic neoplasm, respectively. The anatomic proximity of the biliary tract and the pancreas, the nearly simultaneous development of both organs from the endoderm of the foregut, and the presence of pancreatic exocrine acini within the peribiliary glands surrounding the extrahepatic bile ducts are suggested as causative factors for these similarities. Interestingly, these diseases show "nearly" identical findings at cross-sectional imaging, an observation that further supports this new disease concept. New information obtained with regard to biliary diseases can be used for evaluation of pancreatic abnormalities, and vice versa. In addition, combined genetic and molecular studies may be performed to develop novel therapeutic targets. For both biliary and pancreatic diseases, imaging plays a pivotal role in initial diagnosis, evaluation of treatment response, efficacy testing of novel drugs, and long-term surveillance. PMID- 26824514 TI - Structural Coloration Pigments based on Carbon Modified ZnS@SiO2 Nanospheres with Low-Angle Dependence, High Color Saturation, and Enhanced Stability. AB - Vividly structurally colored pigments produced by employing materials with high indices of refraction such as ZnS, TiO2, or ZrO2 have attracted great attention recently. Generally, pigments with high refractive index based on three dimensional ordered macroporous (3DOM) structures were prepared by a colloidal crystal template method. However, the preparation of 3DOM structures is time consuming. Moreover, it will also lead to iridescent colors. In this work, structurally colored pigments based on carbon-modified core-shell nanospheres of ZnS@SiO2 were prepared by a homogeneous deposition method, followed by a modified Stober method and a calcination process. Compared with conventional method, the pigments prepared in our work shows high color saturation, enhanced stability and low angle dependent. Typical paints composed of pigments and ethanol could be spray coated on any substrates without limitation. These core-shell structural coloration pigments have potential applications for displays, colorimetric sensors, and pigments. PMID- 26824515 TI - Reply. PMID- 26824516 TI - Low serum biotin in Japanese children fed with hydrolysate formula. AB - BACKGROUND: Given that nutritional biotin deficiency in Japanese infants has been reported, a straightforward method for estimating biotin level is needed. The biotin content in infant formula, breast milk, and the sera of infants fed with various types of formula were measured using avidin-binding assay. METHODS: A commercially available ELISA kit was used for the measurement of biotin in 54 types of formula, including hydrolysate formulas for milk allergy, as well as in breast milk and in the sera of 27 infants fed with these formulas. RESULTS: The biotin content reached the recommended value in only five formulas. All of the hydrolysate formulas and more than half of the special formulas contained biotin <0.1 MUg/dL. Serum biotin was low in infants fed only with the hydrolysate formulas, and one of them had alopecia related to biotin deficiency. CONCLUSION: While many were asymptomatic, infants fed with formulas lacking biotin are at risk of developing symptomatic disease. The addition of biotin to breast milk substitutes was finally approved in the middle of 2014, however pediatricians in Japan should still be vigilant with regard to nutritional biotin deficiency in infants for the time being. PMID- 26824517 TI - Ultrasonographic Evaluation of the Effects of Progressive Resistive Exercise in Breast Cancer-Related Lymphedema. AB - OBJECTIVE: To investigate the ultrasonic effects of progressive resistance exercise (PRE) for the treatment of patients with breast cancer-related lymphedema (BCRL). SUBJECTS AND METHOD: The 32 patients with diagnosed BCRL were randomly divided into two groups: the PRE group and the non-PRE group. After complex decongestive physiotherapy, PRE was performed by 0.5 kg dumbbell while wearing a compression stocking or a multilayer bandage to avoid aggravation of the lymphedema in the shoulder and arm. In the first week, the PRE group performed five repetitions of each exercise, twice a day, and the exercise were increased to five repetitions every week during 8 weeks. The thickness of muscle and subcutaneous tissue and circumferences of proximal and distal upper limbs were measured at baseline, 4 weeks, and 8 weeks. Examiners measured the circumference of upper limbs with tape measure, then the thickness of the muscle and subcutaneous tissue were measured by ultrasonography. RESULTS: Muscle thickness of the upper limbs was less in the affected limb than that of the nonaffected limb at pretreatment. The thickness of subcutaneous tissue and circumferences of the arm was more decreased in the PRE group than that of the non-PRE group. The thickness of muscle of the arm was more significantly increased in the PRE group than that of the non-PRE group (p < 0.05). CONCLUSION: For the treatment of patients with BCRL, PRE with complex decongestive physiotherapy did not cause additional swelling, and it reduced arm circumference by decreased subcutaneous tissue thickness and increased muscle thickness. PMID- 26824518 TI - Efficient One-Pot Synthesis of Colloidal Zirconium Oxide Nanoparticles for High Refractive-Index Nanocomposites. AB - Zirconium oxide nanoparticles are promising candidates for optical engineering, photocatalysis, and high-kappa dielectrics. However, reported synthetic methods for the colloidal zirconium oxide nanoparticles use unstable alkoxide precursors and have various other drawbacks, limiting their wide application. Here, we report a facile one-pot method for the synthesis of colloidally stable zirconium oxide nanoparticles. Using a simple solution of zirconium trifluoroacetate in oleylamine, highly stable zirconium oxide nanoparticles have been synthesized with high yield, following a proposed amidization-assisted sol-gel mechanism. The nanoparticles can be readily dispersed in nonpolar solvents, forming a long-term stable transparent solution, which can be further used to fabricate high refractive-index nanocomposites in both monolith and thin-film forms. In addition, the same method has also been extended to the synthesis of titanium oxide nanoparticles, demonstrating its general applicability to all group IVB metal oxide nanoparticles. PMID- 26824519 TI - Estimating the benefit of a second bone anchored hearing implant in unilaterally implanted users with a testband. AB - Conclusion Using a second bone anchored hearing implant (BAHI) mounted on a testband in unilaterally implanted BAHI users to test its potential advantage pre operatively under-estimates the advantage of two BAHIs placed on two implants. Objectives To investigate how well speech understanding with a second BAHI mounted on a testband approaches the benefit of bilaterally implanted BAHIs. Method Prospective study with 16 BAHI users. Eight were implanted unilaterally (group A) and eight were implanted bilaterally (group B). Aided speech understanding was measured. Speech was presented from the front and noise came either from the left, right, or from the front in two conditions for group A (with one BAHI, and with two BAHIs, where the second device was mounted on a testband) and in three conditions for group B (same two conditions as group A, and in addition with both BAHIs mounted on implants). Results Speech understanding in noise improved with the additional device for noise from the side of the first BAHI (+0.7 to +2.1 dB) and decreased for noise from the other side (-1.8 dB to -3.9 dB). Improvements were highest (+2.1 dB, p = 0.016) and disadvantages were smallest (-1.8 dB, p = 0.047) with both BAHIs mounted on implants. Testbands yielded smaller advantages and higher disadvantages of the additional BAHI (average difference = -0.9 dB). PMID- 26824520 TI - gamma-Cyclodextrin capped silver nanoparticles for molecular recognition and enhancement of antibacterial activity of chloramphenicol. AB - Computational studies were conducted to identify the favourable formation of the inclusion complex of chloramphenicol with cyclodextrins. The results of molecular docking and molecular dynamics predicted the strongest interaction of chloramphenicol with gamma-cyclodextrin. Further, the inclusion complex of chloramphenicol with gamma-cyclodextrin was experimentally prepared and a phenomenon of inclusion was verified by using different characterization techniques such as thermogravimetric analysis, differential scanning calorimetry, (1)H nuclear magnetic resonance (NMR) and two dimensional nuclear overhauser effect spectroscopy (NOESY) experiments. From these results it was concluded that gamma-cyclodextrins could be an appropriate cyclodextrin polymer which can be used to functionalize chloramphenicol on the surface of silver nanoparticles. In addition, gamma-cyclodextrin capped silver nanoparticles were synthesized and characterized using UV-visible spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray analysis (EDX), Fourier transform infrared spectroscopy (FTIR) and zeta potential analysis. Molecular recognition of chloramphenicol by these cyclodextrin capped silver nanoparticles was confirmed by surface enhanced raman spectroscopy (SERS) experiments. Synergistic antibacterial effect of chloramphenicol with gamma cyclodextrin capped silver nanoparticles was evaluated against Pseudomonas aeruginosa (ATCC 27853), Enterococcus faecalis (ATCC 5129), Klebsiella pneumoniae (ATCC 700603) and Staphylococcus aureus (ATCC 43300). The results from the antibacterial experiment were favourable thus allowing us to conclude that the approach of modifying organic drug molecules with cyclodextrin capped inorganic silver nanoparticles could help to enhance the antibacterial activity of them. PMID- 26824521 TI - Staufen1 Regulates Multiple Alternative Splicing Events either Positively or Negatively in DM1 Indicating Its Role as a Disease Modifier. AB - Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder caused by an expansion of CUG repeats in the 3' UTR of the DMPK gene. The CUG repeats form aggregates of mutant mRNA, which cause misregulation and/or sequestration of RNA binding proteins, causing aberrant alternative splicing in cells. Previously, we showed that the multi-functional RNA-binding protein Staufen1 (Stau1) was increased in skeletal muscle of DM1 mouse models and patients. We also showed that Stau1 rescues the alternative splicing profile of pre-mRNAs, e.g. the INSR and CLC1, known to be aberrantly spliced in DM1. In order to explore further the potential of Stau1 as a therapeutic target for DM1, we first investigated the mechanism by which Stau1 regulates pre-mRNA alternative splicing. We report here that Stau1 regulates the alternative splicing of exon 11 of the human INSR via binding to Alu elements located in intron 10. Additionally, using a high throughput RT-PCR screen, we have identified numerous Stau1-regulated alternative splicing events in both WT and DM1 myoblasts. A number of these aberrant ASEs in DM1, including INSR exon 11, are rescued by overexpression of Stau1. However, we find other ASEs in DM1 cells, where overexpression of Stau1 shifts the splicing patterns away from WT conditions. Moreover, we uncovered that Stau1-regulated ASEs harbour Alu elements in intronic regions flanking the alternative exon more than non-Stau1 targets. Taken together, these data highlight the broad impact of Stau1 as a splicing regulator and suggest that Stau1 may act as a disease modifier in DM1. PMID- 26824522 TI - Dual T-type and L-type calcium channel blocker exerts beneficial effects in attenuating cardiovascular dysfunction in iron-overloaded thalassaemic mice. AB - NEW FINDINGS: What is the central question of this study? Head-to-head comparison of the therapeutic efficacy among commercial iron chelators and a dual T- (TTCC) and L-type calcium channel (LTCC) blocker on cardiac function, mitochondrial function and the protein expression of cardiac iron transporters in thalassaemic mice in iron-overloaded conditions has not been assessed. What is the main finding and its importance? The dual TTCC and LTCC blocker efonidipine could provide broad beneficial effects in the heart, liver, plasma and mitochondria in both wild-type and thalassaemic mice in iron-overloaded conditions. Its beneficial effects are of the same degree as the three commercial iron chelators currently used clinically. It is possible that efonidipine could be an alternative choice in patients unable to take iron chelators for the treatment of iron-overload conditions. Iron chelation therapy is a standard treatment in thalassaemia patients; however, its poor cardioprotective efficacy and serious side-effects are a cause for concern. Previous studies have shown that treatment with L-type calcium channel (LTCC) blockers or dual T-type calcium channel (TTCC) and LTCC blockers decreases cardiac iron and improves cardiac dysfunction in an iron-overloaded rodent model. Currently, the head-to-head comparison of therapeutic efficacy among commercial iron chelators, a dual TTCC and LTCC blocker and an LTCC blocker on cardiac function, mitochondrial function and the protein expression of cardiac iron transporters in thalassaemic mice in an iron overloaded state has never been investigated. An iron-overloaded state was induced in beta-thalassaemic and wild-type mice. Cardiac iron overload was induced to a greater extent than in a previous study by feeding the mice with an iron-enriched diet for 4 months. Then, an LTCC blocker (amlodipine) or a dual TTCC and LTCC blocker (efonidipine) or one of the commercial iron chelators (deferoxamine, deferasirox or deferiprone) was administered for 1 month with continuous iron feeding. All treatments reduced cardiac iron deposition and improved mitochondrial and cardiac dysfunction in both types of mice. Only efonidipine and the iron chelators reduced liver iron accumulation, liver malondialdehyde and plasma malondialdehyde in these mice. Although all pharmacological interventions reduced cardiac iron deposition, they did not alter the protein expression levels of cardiac iron transporter. These findings indicated that efonidipine provided all benefits to the same degree as the three commercial iron chelators. These findings indicate that a dual TTCC and LTCC blocker could be beneficial for treatment of an iron-overloaded state. PMID- 26824523 TI - Engineering of a Novel Simplified Human Insulin-Like Peptide 5 Agonist. AB - Insulin-like peptide 5 (INSL5) has recently been discovered as only the second orexigenic gut hormone after ghrelin. As we have previously reported, INSL5 is extremely difficult to assemble and oxidize into its two-chain three-disulfide structure. The focus of this study was to generate structure-activity relationships (SARs) of INSL5 and use it to develop a potent and simpler INSL5 mimetic with RXFP4 agonist activity. A series of human and mouse INSL5 (hINSL5/mINSL5) analogues were designed and chemically synthesized, resulting in a chimeric INSL5 analogue exhibiting more than 10-fold higher potency (0.35 nM) at human RXFP4 compared with native hINSL5 (4.57 nM). The SAR study also identified a key residue (K(A15)) in the A-chain of mINSL5 that contributes to improved RXFP4 affinity and potency of mINSL5 compared with hINSL5. This knowledge ultimately led us to engineer a minimized hINSL5 mimetic agonist that retains native hINSL5-like RXFP4 affinity and potency at human RXFP4. This minimized analogue was synthesized in 17.5-fold higher yield and in less time compared with hINSL5. PMID- 26824524 TI - Novelties in Diabetic Retinopathy. AB - Although diabetic retinopathy (DR) remains a leading cause of vision loss, the last decade has brought significant advances in the diagnosis and treatment of this common complication of diabetes mellitus. First, optical coherence tomography allows for noninvasive imaging of the retina, in particular, the macula, with very high resolution, thus facilitating the management of diabetic macular edema. In addition, recent advances in the understanding of the pathophysiology of DR, in particular, the key role of cytokines, such as vascular endothelial growth factor (VEGF), have led to the development of anti-VEGF antibodies for intraocular use. Anti-VEGF therapies have largely replaced laser photocoagulation for the treatment of diabetic macular edema. The benefit of intravitreal anti-VEGF in diabetic macular edema has been proven in numerous large randomized controlled trials. Moreover, a role of inflammation in DR has been recognized, and several mainly steroid-based, anti-inflammatory agents for intravitreal treatment have been shown to be effective. Despite these recent advances, strict systemic control of glycemia remains the cornerstone of the management of DR, significantly reducing ocular complications. This chapter will provide an overview of current and novel concepts of DR and will allude to promising novel therapeutic options for this sight-threatening disease. PMID- 26824525 TI - Rapid Identification of Candidate Genes for Seed Weight Using the SLAF-Seq Method in Brassica napus. AB - Seed weight is a critical and direct trait for oilseed crop seed yield. Understanding its genetic mechanism is of great importance for yield improvement in Brassica napus breeding. Two hundred and fifty doubled haploid lines derived by microspore culture were developed from a cross between a large-seed line G-42 and a small-seed line 7-9. According to the 1000-seed weight (TSW) data, the individual DNA of the heaviest 46 lines and the lightest 47 lines were respectively selected to establish two bulked DNA pools. A new high-throughput sequencing technology, Specific Locus Amplified Fragment Sequencing (SLAF-seq), was used to identify candidate genes of TSW in association analysis combined with bulked segregant analysis (BSA). A total of 1,933 high quality polymorphic SLAF markers were developed and 4 associated markers of TSW were procured. A hot region of ~0.58 Mb at nucleotides 25,401,885-25,985,931 on ChrA09 containing 91 candidate genes was identified as tightly associated with the TSW trait. From annotation information, four genes (GSBRNA2T00037136001, GSBRNA2T00037157001, GSBRNA2T00037129001 and GSBRNA2T00069389001) might be interesting candidate genes that are highly related to seed weight. PMID- 26824527 TI - Transitional Zone Index as a Predictor of the Efficacy of alpha-Blocker and 5alpha-Reductase Inhibitor Combination Therapy in Korean Patients with Benign Prostatic Hyperplasia. AB - INTRODUCTION: We investigated the value of the transitional zone index (TZI) for predicting treatment response to combination therapy involving alpha-blockers and 5alpha-reductase inhibitors for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Symptomatic BPH patients (n = 118) were randomized to receive 0.2 mg tamsulosin alone or with 0.5 mg dutasteride daily for 12 months. The TZI, International Prostate Symptom Scores, maximum urinary flow rates (Qmax), postvoid residual urine volumes, and prostate-specific antigen (PSA) were evaluated at baseline and after 12 months. The groups were subdivided according to a cut-off TZI value of 0.5 to compare treatment-related changes. RESULTS: After 12 months, the combination therapy group had significantly greater decreases in prostate volume (p < 0.001), TZ volume (p < 0.001) and PSA (p < 0.001) than the monotherapy group, regardless of TZI. However, combination therapy resulted in significantly greater Qmax increases (p < 0.001) only in patients with a TZI >=0.5. Multivariate analysis determined that TZI was the strongest independent predictor of the Qmax increase at 12 months in the combination therapy group (beta = 13.7, p < 0.001). CONCLUSIONS: Greater Qmax improvement is expected with combination therapy comprising alpha-blockers and 5alpha-reductase inhibitors for patients with a TZI >=0.5. The TZI may be useful for predicting the Qmax response to combination treatment for BPH. PMID- 26824526 TI - Enzymes for Pancreatic Islet Isolation Impact Chemokine-Production and Polarization of Insulin-Producing beta-Cells with Reduced Functional Survival of Immunoisolated Rat Islet-Allografts as a Consequence. AB - The primary aim of this study was to determine whether normal variations in enzyme-activities of collagenases applied for rat-islet isolation impact longevity of encapsulated islet grafts. Also we studied the functional and immunological properties of rat islets isolated with different enzyme preparations to determine whether this impacts these parameters. Rat-islets were isolated from the pancreas with two different collagenases with commonly accepted collagenase, neutral protease, and clostripain activities. Islets had a similar and acceptable glucose-induced insulin-release profile but a profound statistical significant difference in production of the chemokines IP-10 and Gro-alpha. The islets were studied with nanotomy which is an EM-based technology for unbiased study of ultrastructural features of islets such as cell-cell contacts, endocrine cell condition, ER stress, mitochondrial conditions, and cell polarization. The islet-batch with higher chemokine-production had a lower amount of polarized insulin-producing beta-cells. All islets had more intercellular spaces and less interconnected areas with tight cell-cell junctions when compared to islets in the pancreas. Islet-graft function was studied by implanting encapsulated and free islet grafts in rat recipients. Alginate-based encapsulated grafts isolated with the enzyme-lot inducing higher chemokine production and lower polarization survived for a two-fold shorter period of time. The lower survival-time of the encapsulated grafts was correlated with a higher influx of inflammatory cells at 7 days after implantation. Islets from the same two batches transplanted as free unencapsulated-graft, did not show any difference in survival or function in vivo. Lack of insight in factors contributing to the current lab-to-lab variation in longevity of encapsulated islet-grafts is considered to be a threat for clinical application. Our data suggest that seemingly minor variations in activity of enzymes applied for islet-isolation might contribute to longevity variations of immunoisolated islet-grafts. PMID- 26824528 TI - Patterns of Behaviour, Group Structure and Reproductive Status Predict Levels of Glucocorticoid Metabolites in Zoo-Housed Ring-Tailed Lemurs, Lemur catta. AB - In ring-tailed lemurs, Lemur catta, the factors modulating hypothalamic-pituitary adrenal (HPA) activity differ between wild and semi-free-ranging populations. Here we assess factors modulating HPA activity in ring-tailed lemurs housed in a third environment: the zoo. First we validate an enzyme immunoassay to quantify levels of glucocorticoid (GC) metabolites in the faeces of L. catta. We determine the nature of the female-female dominance hierarchies within each group by computing David's scores and examining these in relation to faecal GC (fGC). Relationships between female age and fGC are assessed to evaluate potential age related confounds. The associations between fGC, numbers of males in a group and reproductive status are explored. Finally, we investigate the value of 7 behaviours in predicting levels of fGC. The study revealed stable linear dominance hierarchies in females within each group. The number of males in a social group together with reproductive status, but not age, influenced fGC. The 7 behavioural variables accounted for 68% of the variance in fGC. The amounts of time an animal spent locomoting and in the inside enclosure were both negative predictors of fGC. The study highlights the flexibility and adaptability of the HPA system in ring-tailed lemurs. PMID- 26824529 TI - Use of an Electrochemical Split Cell Technique to Evaluate the Influence of Shewanella oneidensis Activities on Corrosion of Carbon Steel. AB - Microbially induced corrosion (MIC) is a complex problem that affects various industries. Several techniques have been developed to monitor corrosion and elucidate corrosion mechanisms, including microbiological processes that induce metal deterioration. We used zero resistance ammetry (ZRA) in a split chamber configuration to evaluate the effects of the facultatively anaerobic Fe(III) reducing bacterium Shewanella oneidensis MR-1 on the corrosion of UNS G10180 carbon steel. We show that activities of S. oneidensis inhibit corrosion of steel with which that organism has direct contact. However, when a carbon steel coupon in contact with S. oneidensis was electrically connected to a second coupon that was free of biofilm (in separate chambers of the split chamber assembly), ZRA based measurements indicated that current moved from the S. oneidensis-containing chamber to the cell-free chamber. This electron transfer enhanced the O2 reduction reaction on the coupon deployed in the cell free chamber, and consequently, enhanced oxidation and corrosion of that electrode. Our results illustrate a novel mechanism for MIC in cases where metal surfaces are heterogeneously covered by biofilms. PMID- 26824530 TI - On-Demand Single Photons with High Extraction Efficiency and Near-Unity Indistinguishability from a Resonantly Driven Quantum Dot in a Micropillar. AB - Scalable photonic quantum technologies require on-demand single-photon sources with simultaneously high levels of purity, indistinguishability, and efficiency. These key features, however, have only been demonstrated separately in previous experiments. Here, by s-shell pulsed resonant excitation of a Purcell-enhanced quantum dot-micropillar system, we deterministically generate resonance fluorescence single photons which, at pi pulse excitation, have an extraction efficiency of 66%, single-photon purity of 99.1%, and photon indistinguishability of 98.5%. Such a single-photon source for the first time combines the features of high efficiency and near-perfect levels of purity and indistinguishabilty, and thus opens the way to multiphoton experiments with semiconductor quantum dots. PMID- 26824531 TI - Measuring and Suppressing Quantum State Leakage in a Superconducting Qubit. AB - Leakage errors occur when a quantum system leaves the two-level qubit subspace. Reducing these errors is critically important for quantum error correction to be viable. To quantify leakage errors, we use randomized benchmarking in conjunction with measurement of the leakage population. We characterize single qubit gates in a superconducting qubit, and by refining our use of derivative reduction by adiabatic gate pulse shaping along with detuning of the pulses, we obtain gate errors consistently below 10^{-3} and leakage rates at the 10^{-5} level. With the control optimized, we find that a significant portion of the remaining leakage is due to incoherent heating of the qubit. PMID- 26824532 TI - Renormalizing Entanglement Distillation. AB - Entanglement distillation refers to the task of transforming a collection of weakly entangled pairs into fewer highly entangled ones. It is a core ingredient in quantum repeater protocols, which are needed to transmit entanglement over arbitrary distances in order to realize quantum key distribution schemes. Usually, it is assumed that the initial entangled pairs are identically and independently distributed and are uncorrelated with each other, an assumption that might not be reasonable at all in any entanglement generation process involving memory channels. Here, we introduce a framework that captures entanglement distillation in the presence of natural correlations arising from memory channels. Conceptually, we bring together ideas from condensed-matter physics-ideas from renormalization and matrix-product states and operators-with those of local entanglement manipulation, Markov chain mixing, and quantum error correction. We identify meaningful parameter regions for which we prove convergence to maximally entangled states, arising as the fixed points of a matrix-product operator renormalization flow. PMID- 26824533 TI - Quantifying Non-Markovianity with Temporal Steering. AB - Einstein-Podolsky-Rosen (EPR) steering is a type of quantum correlation which allows one to remotely prepare, or steer, the state of a distant quantum system. While EPR steering can be thought of as a purely spatial correlation, there does exist a temporal analogue, in the form of single-system temporal steering. However, a precise quantification of such temporal steering has been lacking. Here, we show that it can be measured, via semidefinite programing, with a temporal steerable weight, in direct analogy to the recently proposed EPR steerable weight. We find a useful property of the temporal steerable weight in that it is a nonincreasing function under completely positive trace-preserving maps and can be used to define a sufficient and practical measure of strong non Markovianity. PMID- 26824534 TI - First and Second Law of Thermodynamics at Strong Coupling. AB - For a small driven system coupled strongly to a heat bath, internal energy and exchanged heat are identified such that they obey the usual additive form of the first law. By identifying this exchanged heat with the entropy change of the bath, the total entropy production is shown to obey an integral fluctuation theorem on the trajectory level implying the second law in the form of a Clausius inequalilty on the ensemble level. In this Hamiltonian approach, the assumption of an initially uncorrelated state is not required. The conditions under which the proposed identification of heat is unique and experimentally accessible are clarified. PMID- 26824535 TI - Analytic Solution of the Boltzmann Equation in an Expanding System. AB - For a massless gas with a constant cross section in a homogeneous, isotropically expanding spacetime we reformulate the relativistic Boltzmann equation as a set of nonlinear coupled moment equations. For a particular initial condition this set can be solved exactly, yielding the first analytical solution of the Boltzmann equation for an expanding system. The nonequilibrium behavior of this relativistic gas can be mapped onto that of a homogeneous, static nonrelativistic gas of Maxwell molecules. PMID- 26824537 TI - Ionization of Atoms by Slow Heavy Particles, Including Dark Matter. AB - Atoms and molecules can become ionized during the scattering of a slow, heavy particle off a bound electron. Such an interaction involving leptophilic weakly interacting massive particles (WIMPs) is a promising possible explanation for the anomalous 9sigma annual modulation in the DAMA dark matter direct detection experiment [R. Bernabei et al., Eur. Phys. J. C 73, 2648 (2013)]. We demonstrate the applicability of the Born approximation for such an interaction by showing its equivalence to the semiclassical adiabatic treatment of atomic ionization by slow-moving WIMPs. Conventional wisdom has it that the ionization probability for such a process should be exponentially small. We show, however, that due to nonanalytic, cusplike behavior of Coulomb functions close to the nucleus this suppression is removed, leading to an effective atomic structure enhancement. We also show that electron relativistic effects actually give the dominant contribution to such a process, enhancing the differential cross section by up to 1000 times. PMID- 26824538 TI - Cavity-Free Scheme for Nondestructive Detection of a Single Optical Photon. AB - Detecting a single photon without absorbing it is a long-standing challenge in quantum optics. All experiments demonstrating the nondestructive detection of a photon make use of a high quality cavity. We present a cavity-free scheme for nondestructive single-photon detection. By pumping a nonlinear medium we implement an interfield Rabi oscillation which leads to a ~pi phase shift on a weak probe coherent laser field in the presence of a single signal photon without destroying the signal photon. Our cavity-free scheme operates with a fast intrinsic time scale in comparison with similar cavity-based schemes. We implement a full real-space multimode numerical analysis of the interacting photonic modes and confirm the validity of our nondestructive scheme in the multimode case. PMID- 26824536 TI - Spectroscopic Quadrupole Moments in {96,98}Sr: Evidence for Shape Coexistence in Neutron-Rich Strontium Isotopes at N=60. AB - Neutron-rich {96,98}Sr isotopes have been investigated by safe Coulomb excitation of radioactive beams at the REX-ISOLDE facility. Reduced transition probabilities and spectroscopic quadrupole moments have been extracted from the differential Coulomb excitation cross sections. These results allow, for the first time, the drawing of definite conclusions about the shape coexistence of highly deformed prolate and spherical configurations. In particular, a very small mixing between the coexisting states is observed, contrary to other mass regions where strong mixing is present. Experimental results have been compared to beyond-mean-field calculations using the Gogny D1S interaction in a five-dimensional collective Hamiltonian formalism, which reproduce the shape change at N=60. PMID- 26824540 TI - Spectral Properties of Dirac Billiards at the van Hove Singularities. AB - We study distributions of the ratios of level spacings of rectangular and Africa shaped superconducting microwave resonators containing circular scatterers on a triangular grid, so-called Dirac billiards (DBs). The high-precision measurements allowed the determination of, respectively, all 1651 and 1823 eigenfrequencies in the first two bands. The resonance densities are similar to that of graphene. They exhibit two sharp peaks at the van Hove singularities which separate the band structure into regions with a linear and a quadratic dispersion relation, respectively. In the vicinity of the van Hove singularities we observe rapid changes in, e.g., the wave function structure. Accordingly, we question whether the spectral properties are there still determined by the shapes of the DBs. The commonly used statistical measures are no longer applicable; however, we demonstrate in this Letter that the ratio distributions provide suitable measures. PMID- 26824539 TI - Zero-Area Single-Photon Pulses. AB - Broadband single photons are usually considered not to couple efficiently to atomic gases because of the large mismatch in bandwidth. Contrary to this intuitive picture, here we demonstrate that the interaction of ultrashort single photons with a dense resonant atomic sample deeply modifies the temporal shape of their wave packet mode without degrading their nonclassical character, and effectively generates zero-area single-photon pulses. This is a clear signature of strong transient coupling between single broadband (THz-level) light quanta and atoms, with intriguing fundamental implications and possible new applications to the storage of quantum information. PMID- 26824541 TI - Observation of a Single-Beam Gradient Force Acoustical Trap for Elastic Particles: Acoustical Tweezers. AB - We demonstrate the trapping of elastic particles by the large gradient force of a single acoustical beam in three dimensions. Acoustical tweezers can push, pull and accurately control both the position and the forces exerted on a unique particle. Forces in excess of 1 micronewton were exerted on polystyrene beads in the submillimeter range. A beam intensity less than 50 W/cm^{2} was required, ensuring damage-free trapping conditions. The large spectrum of frequencies covered by coherent ultrasonic sources provides a wide variety of manipulation possibilities from macroscopic to microscopic length scales. Our observations could open the way to important applications, in particular, in biology and biophysics at the cellular scale and for the design of acoustical machines in microfluidic environments. PMID- 26824542 TI - Prandtl-Number Dependence of Heat Transport in Laminar Horizontal Convection. AB - We report the Prandtl-number (Pr) and Rayleigh-number (Ra) dependencies of the Reynolds number (Re) and mean convective heat transport, measured by the Nusselt number (Nu), in horizontal convection (HC) systems, where the heat supply and removal are provided exclusively through a lower horizontal surface of a fluid layer. For laminar HC, we find that Re~Ra^{2/5}Pr^{-4/5}, Nu~Ra^{1/5}Pr^{1/10} with a transition to Re~Ra^{1/2}Pr^{-1}, Nu~Ra^{1/4}Pr^{0} for large Pr. The results are based on direct numerical simulations for Ra from 3*10^{8} to 5*10^{10} and Pr from 0.05 to 50 and are explained by applying the Grossmann Lohse approach [J. Fluid Mech. 407, 27 (2000)] transferred from the case of Rayleigh-Benard convection to the case of laminar HC. PMID- 26824543 TI - Consistent Hydrodynamics for Phase Field Crystals. AB - We use the amplitude expansion in the phase field crystal framework to formulate an approach where the fields describing the microscopic structure of the material are coupled to a hydrodynamic velocity field. The model is shown to reduce to the well-known macroscopic theories in appropriate limits, including compressible Navier-Stokes and wave equations. Moreover, we show that the dynamics proposed allows for long wavelength phonon modes and demonstrate the theory numerically showing that the elastic excitations in the system are relaxed through phonon emission. PMID- 26824544 TI - Generation of Phase-Locked Pulses from a Seeded Free-Electron Laser. AB - In a coherent control experiment, light pulses are used to guide the real-time evolution of a quantum system. This requires the coherence and the control of the pulses' electric-field carrier waves. In this work, we use frequency-domain interferometry to demonstrate the mutual coherence of time-delayed pulses generated by an extreme ultraviolet seeded free-electron laser. Furthermore, we use the driving seed laser to lock and precisely control the relative phase between the two free-electron laser pulses. This new capability opens the way to a multitude of coherent control experiments, which will take advantage of the high intensity, short wavelength, and short duration of the pulses generated by seeded free-electron lasers. PMID- 26824545 TI - Thermodynamic Study on Plasma Expansion along a Divergent Magnetic Field. AB - Thermodynamic properties are revisited for electrons that are governed by nonlocal electron energy probability functions in a plasma of low collisionality. Measurements in a laboratory helicon double layer experiment have shown that the effective electron temperature and density show a polytropic correlation with an index of gamma_{e}=1.17+/-0.02 along the divergent magnetic field, implying a nearly isothermal plasma (gamma_{e}=1) with heat being brought into the system. However, the evolution of electrons along the divergent magnetic field is essentially an adiabatic process, which should have a gamma_{e}=5/3. The reason for this apparent contradiction is that the nearly collisionless plasma is very far from local thermodynamic equilibrium and the electrons behave nonlocally. The corresponding effective electron enthalpy has a conservation relation with the potential energy, which verifies that there is no heat transferred into the system during the electron evolution. The electrons are shown in nonlocal momentum equilibrium under the electric field and the gradient of the effective electron pressure. The convective momentum of ions, which can be assumed as a cold species, is determined by the effective electron pressure and the effective electron enthalpy is shown to be the source for ion acceleration. For these nearly collisionless plasmas, the use of traditional thermodynamic concepts can lead to very erroneous conclusions regarding the thermal conductivity. PMID- 26824546 TI - Universal Coarsening Dynamics of a Quenched Ferromagnetic Spin-1 Condensate. AB - We demonstrate that a quasi-two-dimensional spin-1 condensate quenched to a ferromagnetic phase undergoes universal coarsening in its late time dynamics. The quench can be implemented by a sudden change in the applied magnetic field and, depending on the final value, the ferromagnetic phase has easy-axis (Ising) or easy-plane (XY) symmetry, with different dynamical critical exponents. Our results for the easy-plane phase reveal a fractal domain structure and the crucial role of polar-core spin vortices in the coarsening dynamics. PMID- 26824547 TI - Two Dimensional Ice from First Principles: Structures and Phase Transitions. AB - Despite relevance to disparate areas such as cloud microphysics and tribology, major gaps in the understanding of the structures and phase transitions of low dimensional water ice remain. Here, we report a first principles study of confined 2D ice as a function of pressure. We find that at ambient pressure hexagonal and pentagonal monolayer structures are the two lowest enthalpy phases identified. Upon mild compression, the pentagonal structure becomes the most stable and persists up to ~2 GPa, at which point the square and rhombic phases are stable. The square phase agrees with recent experimental observations of square ice confined within graphene sheets. This work provides a fresh perspective on 2D confined ice, highlighting the sensitivity of the structures observed to both the confining pressure and the width. PMID- 26824548 TI - Anomalous Depletion of Pore-Confined Carbon Dioxide upon Cooling below the Bulk Triple Point: An In Situ Neutron Diffraction Study. AB - The phase behavior of sorbed CO{2} in an ordered mesoporous silica sample (SBA 15) was studied by neutron diffraction. Surprisingly, upon cooling our sample below the bulk critical point, confined CO{2} molecules neither freeze nor remain liquid as expected, but escape from the pores. The phenomenon has additionally been confirmed gravimetrically. The process is reversible and during heating CO{2} refills the pores, albeit with hysteresis. This depletion was for the first time observed in an ordered mesoporous molecular sieve and provides new insight on the phase behavior of nanoconfined fluids. PMID- 26824549 TI - Ab initio Prediction of Martensitic and Intermartensitic Phase Boundaries in Ni Mn-Ga. AB - Despite the importance of martensitic transformations of Ni-Mn-Ga Heusler alloys for their magnetocaloric and shape-memory properties, the martensitic part of their phase diagrams is not well determined. Using an ab initio approach that includes the interplay of lattice and vibrational degrees of freedom we identify an intermartensitic transformation between a modulated and a nonmodulated phase as a function of excess Ni and Mn content. Based on an evaluation of the theoretical findings and experimental x-ray diffraction data for Mn-rich alloys, we are able to predict the phase diagram for Ni-rich alloys. In contrast to other mechanisms discussed for various material systems in the literature, we herewith show that the intermartensitic transformation can be understood solely using thermodynamic concepts. PMID- 26824550 TI - Hybrid Percolation Transition in Cluster Merging Processes: Continuously Varying Exponents. AB - Consider growing a network, in which every new connection is made between two disconnected nodes. At least one node is chosen randomly from a subset consisting of g fraction of the entire population in the smallest clusters. Here we show that this simple strategy for improving connection exhibits a more unusual phase transition, namely a hybrid percolation transition exhibiting the properties of both first-order and second-order phase transitions. The cluster size distribution of finite clusters at a transition point exhibits power-law behavior with a continuously varying exponent tau in the range 2 0.05). Maximum peak loads at endplate failure for static and expandable spacers were 1764 N (+/- 966 N) and 2284 N (+/- 949 N), respectively (p <= 0.05). The expandable spacer consistently produced greater desired distraction than was created by the static spacer in the foam-block model (p <= 0.05). Distraction created by fully expanding the spacer was significantly greater than the predetermined goals of 2 mm and 3 mm (p <= 0.05). CONCLUSIONS The current investigation shows that increased trialing required for a static spacer may lead to additional iatrogenic endplate damage, resulting in less distraction and increased propensity for postoperative implant subsidence secondary to endplate disruption. PMID- 26824584 TI - Differences between C3-4 and other subaxial levels of cervical disc arthroplasty: more heterotopic ossification at the 5-year follow-up. AB - OBJECTIVE Several large-scale clinical trials demonstrate the efficacy of 1- and 2-level cervical disc arthroplasty (CDA) for degenerative disc disease (DDD) in the subaxial cervical spine, while other studies reveal that during physiological neck flexion, the C4-5 and C5-6 discs account for more motion than the C3-4 level, causing more DDD. This study aimed to compare the results of CDA at different levels. METHODS After a review of the medical records, 94 consecutive patients who underwent single-level CDA were divided into the C3-4 and non-C3-4 CDA groups (i.e., those including C4-5, C5-6, and C6-7). Clinical outcomes were measured using the visual analog scale for neck and arm pain and by the Japanese Orthopaedic Association scores. Postoperative range of motion (ROM) and heterotopic ossification (HO) were determined by radiography and CT, respectively. RESULTS Eighty-eight patients (93.6%; mean age 45.62 +/- 10.91 years), including 41 (46.6%) female patients, underwent a mean follow-up of 4.90 +/- 1.13 years. There were 11 patients in the C3-4 CDA group and 77 in the non-C3 4 CDA group. Both groups had significantly improved clinical outcomes at each time point after the surgery. The mean preoperative (7.75 degrees vs 7.03 degrees ; p = 0.58) and postoperative (8.18 degrees vs 8.45 degrees ; p = 0.59) ROMs were similar in both groups. The C3-4 CDA group had significantly greater prevalence (90.9% vs 58.44%; p = 0.02) and higher severity grades (2.27 +/- 0.3 vs 0.97 +/- 0.99; p = 0.0001) of HO. CONCLUSIONS Although CDA at C3-4 was infrequent, the improved clinical outcomes of CDA were similar at C3-4 to that in the other subaxial levels of the cervical spine at the approximately 5-year follow-ups. In this Asian population, who had a propensity to have ossification of the posterior longitudinal ligament, there was more HO formation in patients who received CDA at the C3-4 level than in other subaxial levels of the cervical spine. While the type of artificial discs could have confounded the issue, future studies with more patients are required to corroborate the phenomenon. PMID- 26824585 TI - Emergency room resource utilization by patients with low-back pain. AB - OBJECTIVE The objective of this study was to determine factors associated with admission to the hospital through the emergency room (ER) for patients with a primary diagnosis of low-back pain (LBP). The authors further evaluated the impact of ER admission and patient characteristics on mortality, discharge disposition, and hospital length of stay. METHODS The authors conducted a retrospective analysis of patients with LBP discharged from hospitals according to the Nationwide Inpatient Sample (NIS) between 1998 and 2007. Univariate comparisons of patient characteristics according to the type of admission (ER versus non-ER) were conducted. Multivariate analysis evaluated factors associated with an ER admission, risk of mortality, and nonroutine discharge. RESULTS According to the NIS, approximately 183,151 patients with a primary diagnosis of LBP were discharged from US hospitals between 1998 and 2007. During this period, an average of 65% of these patients were admitted through the ER, with a significant increase from 1998 (54%) to 2005 (71%). Multivariate analysis revealed that uninsured patients (OR 2.1, 95% CI 1.7-2.6, p < 0.0001) and African American patients (OR 1.5, 95% CI 1.2-1.7, p < 0.0001) were significantly more likely to be admitted through the ER than private insurance patients or Caucasian patients, respectively. Additionally, a moderate but statistically significant increase in the likelihood of ER admission was noted for patients with more preexisting comorbidities (OR 1.1, 95% CI 1.0-1.2, p < 0.001). An 11% incremental increase in the odds of admission through the ER was observed with each year increment (OR 1.1, 95% CI 1.0-1.2, p < 0.001). Highest income patients ($45,000+) were more likely to be admitted through the ER (OR 1.3, 95% CI 1.1-1.6, p = 0.007) than the lowest income cohort. While ER admission did not impact the risk of mortality (OR 0.95, 95% CI 0.60-1.51, p = 0.84), it increased the odds of a nonroutine discharge (OR 1.39, 95% CI 1.26-1.53, p < 0.0001). CONCLUSIONS A significant majority of patients discharged from hospitals in the US from 1998 to 2007 with a primary diagnosis of LBP were admitted through the ER, with more patients being admitted via this route each year. These patients were less likely to be discharged directly home compared with patients with LBP who were not admitted through the ER. Uninsured and African American patients with LBP were more likely to be admitted through the ER than their counterparts, as were patients with more preexisting health problems. Interestingly, patients with LBP at the highest income levels were more likely to be admitted through hospital ERs. The findings suggest that socioeconomic factors may play a role in the utilization of ER resources by patients with LBP, which in turn appears to impact at least the short-term outcome of these patients. PMID- 26824586 TI - Imaging symptomatic bone morphogenetic protein-2-induced heterotopic bone formation within the spinal canal: case report. AB - Heterotopic bone formation within the spinal canal is a known complication of bone morphogenetic protein-2 (BMP-2) and presents a clinical and surgical challenge. Imaging modalities are routinely used for operative planning in this setting. Here, the authors present the case of a 59-year-old woman with cauda equina syndrome following intraoperative BMP-2 administration. Plain film myelographic studies showed a region of severe stenosis that was underappreciated on CT myelography due to a heterotopic bony lesion mimicking the dorsal aspect of a circumferentially patent thecal sac. When evaluating spinal stenosis under these circumstances, it is important to carefully consider plain myelographic images in addition to postmyelography CT images as the latter may underestimate the true degree of stenosis due to the potentially similar radiographic appearances of evolving BMP-2-induced heterotopic bone and intrathecal contrast. Alternatively, comparison of sequentially acquired noncontrast CT scans with CT myelographic images may also assist in distinguishing BMP-2-induced heterotopic bony lesions from the thecal sac. Further studies are needed to elucidate the roles of the available imaging techniques in this setting and to characterize the connection between the radiographic and histological appearances of BMP-2-induced heterotopic bone. PMID- 26824587 TI - Seven-year cost-effectiveness of ProDisc-C total disc replacement: results from investigational device exemption and post-approval studies. AB - OBJECTIVE The purpose of this study was to evaluate the 7-year cost-effectiveness of cervical total disc replacement (CTDR) versus anterior cervical discectomy and fusion (ACDF) for the treatment of patients with single-level symptomatic degenerative disc disease. A change in the spending trajectory for spine care is to be achieved, in part, through the selection of interventions that have been proven effective yet cost less than other options. This analysis complements and builds upon findings from other cost-effectiveness evaluations of CTDR through the use of long-term, patient-level data from a randomized study. METHODS This was a 7-year health economic evaluation comparing CTDR versus ACDF from the US commercial payer perspective. Prospectively collected health care resource utilization and treatment effects (quality-adjusted life years [QALYs]) were obtained from individual patient-level adverse event reports and SF-36 data, respectively, from the randomized, multicenter ProDisc-C total disc replacement investigational device exemption (IDE) study and post-approval study. Statistical distributions for unit costs were derived from a commercial claims database and applied using Monte Carlo simulation. Patient-level costs and effects were modeled via multivariate probabilistic analysis. Confidence intervals for 7-year costs, effects, and net monetary benefit (NMB) were obtained using the nonparametric percentile method from results of 10,000 bootstrap simulations. The robustness of results was assessed through scenario analysis and within a parametric regression model controlling for baseline variables. RESULTS Seven year follow-up data were available for more than 70% of the 209 randomized patients. In the base-case analysis, CTDR resulted in mean per-patient cost savings of $12,789 (95% CI $5362-$20,856) and per-patient QALY gains of 0.16 (95% CI -0.073 to 0.39) compared with ACDF over 7 years. CTDR was more effective and less costly in 90.8% of probabilistic simulations. CTDR was cost-effective in 99.8% of sensitivity analysis simulations and generated a mean incremental NMB of $20,679 (95% CI $6053-$35,377) per patient at a willingness-to-pay threshold of $50,000/QALY. CONCLUSIONS Based on this modeling evaluation, CTDR was found to be more effective and less costly over a 7-year time horizon for patients with single-level symptomatic degenerative disc disease. These results are robust across a range of scenarios and perspectives and are intended to support value based decision making. PMID- 26824588 TI - Direct-trauma model of posttraumatic syringomyelia with a computer-controlled motorized spinal cord impactor. AB - OBJECTIVE The pathogenesis of posttraumatic syringomyelia remains enigmatic and is not adequately explained by current theories. Experimental investigations require a reproducible animal model that replicates the human condition. Current animal models are imperfect because of their low reliability, severe neurological deficits, or dissimilar mechanism of injury. The objective of this study was to develop a reproducible rodent model of posttraumatic syringomyelia using a spinal cord impactor that produces an injury that more closely mimics the human condition and does not produce severe neurological deficits. METHODS The study consisted of 2 parts. Seventy animals were studied overall: 20 in Experiment 1 and 48 in Experiment 2 after two rats with severe deficits were killed early. Experiment 1 aimed to determine the optimal force setting for inducing a cystic cavity without neurological deficits using a computer-controlled motorized spinal cord impactor. Twenty animals received an impact that ranged from 50 to 150 kDyn. Using the optimal force for producing an initial cyst determined from Experiment 1, Experiment 2 aimed to compare the progression of cavities in animals with and those without arachnoiditis induced by kaolin. Forty-eight animals were killed at 1, 3, 6, or 12 weeks after syrinx induction. Measurements of cavity size and maximum anteroposterior and lateral diameters were evaluated using light microscopy. RESULTS In Experiment 1, cavities were present in 95% of the animals. The duration of limb weakness and spinal cord cavity size correlated with the delivered force. The optimal force chosen for Experiment 2 was 75 kDyn. In Experiment 2, cavities occurred in 92% of the animals. Animals in the kaolin groups developed larger cavities and more vacuolations and enlarged perivascular spaces than those in the nonkaolin groups. CONCLUSIONS This impact model reliably produces cavities that resemble human posttraumatic syringomyelia and is suitable for further study of posttraumatic syringomyelia pathophysiology. PMID- 26824589 TI - Letter to the Editor: Failure of single-level percutaneous endoscopic lumbar discectomy: a challenging clinical dilemma. PMID- 26824590 TI - Performance predictors of brain-computer interfaces in patients with amyotrophic lateral sclerosis. AB - OBJECTIVE: Patients with amyotrophic lateral sclerosis (ALS) may benefit from brain-computer interfaces (BCI), but the utility of such devices likely will have to account for the functional, cognitive, and behavioral heterogeneity of this neurodegenerative disorder. APPROACH: In this study, a heterogeneous group of patients with ALS participated in a study on BCI based on the P300 event related potential and motor-imagery. RESULTS: The presence of cognitive impairment in these patients significantly reduced the quality of the control signals required to use these communication systems, subsequently impairing performance, regardless of progression of physical symptoms. Loss in performance among the cognitively impaired was accompanied by a decrease in the signal-to-noise ratio of task-relevant EEG band power. There was also evidence that behavioral dysfunction negatively affects P300 speller performance. Finally, older participants achieved better performance on the P300 system than the motor imagery system, indicating a preference of BCI paradigm with age. SIGNIFICANCE: These findings highlight the importance of considering the heterogeneity of disease when designing BCI augmentative and alternative communication devices for clinical applications. PMID- 26824591 TI - Synthesis of Nanocrystalline TiOF2 Embedded in a Carbonaceous Matrix from TiF4 and D-Fructose. AB - Nanostructured titanium oxide difluoride embedded in a matrix of amorphous carbon was synthesized by pyrolysis of D-fructose in the presence of titanium tetrafluoride (optimal Ti/fructose molar ratio = 5.5), both in the solid state at ca. 150 degrees C and in suspension of 1,2-dichloroethane at reflux temperature. The resulting solid materials were characterized by powder X-ray diffraction (PXRD), transmission electron microscopy (TEM), and elemental analysis. In every case, PXRD and TEM data indicated the presence of an unique crystalline phase (TiOF2) embedded in a light matrix (amorphous carbon). The average crystal size of the powder can be regulated by varying the reaction time. PMID- 26824592 TI - In the name of brevity: The problem with binary HIV risk categories. AB - According to the 'Consolidated Guidelines on HIV Prevention, Diagnosis, Treatment and Care for Key Populations' there are five groups of people at elevated risk of HIV, including 'transgender women or transgender men who have receptive anal sex with men'. Although cost effectiveness strategies and best practice lessons recommend targeting specific populations for HIV prevention, existing risk categories lack specificity, and may in fact cause further confusion. Existing categories of risk often perpetuate notions of gender and sexuality that can erroneously exclude, alienate, and stigmatise those who are at the highest risk and thus should be prioritised. We review the troubled history of the MSM category and the problematic conflation of trans feminine individuals and MSM in much of the existing HIV literature, and how this practice has stymied progress in slowing the HIV epidemic in the most at-risk groups, including those who do not fit neatly into binary notions of gender and sex. We draw from examples in the field, specifically among trans feminine people in Beirut and San Francisco, to illustrate the lived experiences of individuals whose identities may not fit into Euro-Atlantic constructs of HIV prevention categories. PMID- 26824593 TI - Surgical results of cranioplasty with a polymethylmethacrylate customized cranial implant in pediatric patients: a single-center experience. AB - OBJECTIVE Cranioplasty is a reconstructive procedure used to restore skull anatomy and repair skull defects. Optimal skull reconstruction is a challenge for neurosurgeons, and the strategy used to achieve the best result remains a topic of debate, especially in pediatric patients for whom the continuing skull growth makes the choice of material more difficult. When the native bone flap, which is universally accepted as the preferred option in pediatric patients, is unavailable, the authors' choice of prosthetic material is a polymethylmethacrylate (PMMA) implant designed using a custom-made technique. In this paper the authors present the results of their clinical series of 12 custom made PMMA implants in pediatric patients. METHODS A retrospective study of the patients who had undergone cranioplasty at Gaslini Children's Hospital between 2006 and 2013 was conducted. A total of 12 consecutive cranioplasties in 12 patients was reviewed, in which a patient-specific PMMA implant was manufactured using a virtual 3D model and then transformed into a physical model using selective laser sintering or 3D printing. All patients or parents were administered a questionnaire to assess how the patient/parent judged the aesthetic result. RESULTS Patient age at craniectomy ranged from 5 months to 12.5 years, with a mean age of 84.33 months at cranioplasty. The mean extension of the custom-made plastic was 56.83 cm(2). The mean time between craniectomy and cranioplasty was 9.25 months. The mean follow-up duration was 55.7 months. No major complications were recorded; 3 patients experienced minor/moderate complications (prosthesis dislocation, granuloma formation, and fluid collection). CONCLUSIONS In this patient series, PMMA resulted in an extremely low complication rate and the custom-made technique was associated with an excellent grade of patient or parent satisfaction on long-term follow up. PMID- 26824594 TI - A case of giant fetal intracranial capillary hemangioma cured with propranolol. AB - Fetal brain tumors are rare. This report describes a giant posterior fossa capillary hemangioma treated with 3 mg/kg/day of propranolol for 6 months. Total regression was confirmed at 1 year, and no additional tumors were observed during the subsequent 2 years. No side effects relating to the use of this drug were detected; thus, the authors believe that propranolol may be useful for treating all intracranial capillary hemangiomas. PMID- 26824596 TI - Letter to the Editor: Bridging the gap between administrative data and clinical observations. PMID- 26824595 TI - Randomized clinical trial of acetazolamide administration and/or prone positioning in mitigating wound complications following untethering surgeries. AB - OBJECTIVE No evidence-based guideline has been approved for the postoperative management of pediatric patients with tethered cord syndrome (TCS). The purpose of this randomized clinical trial was to evaluate the effectiveness of prone positioning and acetazolamide administration on complication rates following spinal cord untethering surgeries. METHODS From October 2012 to February 2015, patients with a primary diagnosis of TCS who were admitted to the Children's Medical Center Hospital of Iran were randomly allocated to 1 of 4 intervention modality groups postoperatively: 1) Group A, acetazolamide administration for 10 days; 2) Group B, prone positioning for 10 days; 3) Group C, acetazolamide administration and prone positioning for 10 days; and 4) Group D, no intervention. CSF leakage, CSF collection, wound dehiscence, operative site infection, and secondary surgical wound repair were considered failure. RESULTS A total of 161 patients were enrolled in this study (Group A, n = 39 [24.2%]; Group B, n = 41 [25.5%]; Group C, n = 39 [24.2%]; and Group D, n = 42 [26.1%]). The overall failure rate was 12.42% (20 patients). Complication rates through pooled analyses were as follows: CSF leakage (n = 9, 5.6%), CSF collection (n = 12, 7.5%), wound dehiscence (n = 2, 1.2%), and infection of operation site (n = 3, 1.9%). Two patients (1.2%) required surgical secondary wound repair due to complications. CSF leakage and collection rates were significantly lower in patients who underwent prone positioning (p = 0.042 and 0.036, respectively). The administration of acetazolamide, either isolated or in combination with prone positioning, not only could not significantly lower the complication rates, but also added the burden of side effects. CONCLUSIONS The current study demonstrates the possible role of prone positioning in mitigating the complication rates subsequent to untethering surgeries. Clinical trial registration no.: NCT01867268 ( clinicaltrials.gov ). PMID- 26824597 TI - Hypophosphatemic rickets and craniosynostosis: a multicenter case series. AB - OBJECTIVE This study examines a series of patients with hypophosphatemic rickets and craniosynostosis to characterize the clinical course and associated craniofacial anomalies. METHODS A 20-year retrospective review identified patients with hypophosphatemic rickets and secondary craniosynostosis at 3 major craniofacial centers. Parameters examined included sex, age at diagnosis of head shape anomaly, affected sutures, etiology of rickets, presenting symptoms, number and type of surgical interventions, and associated diagnoses. A review of the literature was performed to optimize treatment recommendations. RESULTS Ten patients were identified (8 males, 2 females). Age at presentation ranged from 1 to 9 years. The most commonly affected suture was the sagittal (6/10 patients). Etiologies included antacid-induced rickets, autosomal dominant hypophosphatemic rickets, and X-linked hypophosphatemic (XLH) rickets. Nine patients had undergone at least 1 cranial vault remodeling (CVR) surgery. Three patients underwent subsequent surgeries in later years. Four patients underwent formal intracranial pressure (ICP) monitoring, 3 of which revealed elevated ICP. Three patients were diagnosed with a Chiari Type I malformation. CONCLUSIONS Secondary craniosynostosis develops postnatally due to metabolic or mechanical factors. The most common metabolic cause is hypophosphatemic rickets, which has a variety of etiologies. Head shape changes occur later and with a more heterogeneous presentation compared with that of primary craniosynostosis. CVR may be required to prevent or relieve elevated ICP and abnormalities of the cranial vault. Children with hypophosphatemic rickets who develop head shape abnormalities should be promptly referred to a craniofacial specialist. PMID- 26824598 TI - Editorial: Post-untethering positioning and diuresis. PMID- 26824599 TI - Rural-Urban Inequity in Unmet Obstetric Needs and Functionality of Emergency Obstetric Care Services in a Zambian District. AB - BACKGROUND: Zambia has a high maternal mortality ratio, 398/100,000 live births. Few pregnant women access emergency obstetric care services to handle complications at childbirth. We aimed to assess the deficit in life-saving obstetric services in the rural and urban areas of Kapiri Mposhi district. METHOD: A cross-sectional survey was conducted in 2011 as part of the 'Response to Accountable priority setting for Trust in health systems' (REACT) project. Data on all childbirths that occurred in emergency obstetric care facilities in 2010 were obtained retrospectively. Sources of information included registers from maternity ward admission, delivery and operation theatre, and case records. Data included age, parity, mode of delivery, obstetric complications, and outcome of mother and the newborn. An approach using estimated major obstetric interventions expected but not done in health facilities was used to assess deficit of life-saving interventions in urban and rural areas. RESULTS: A total of 2114 urban and 1226 rural childbirths occurring in emergency obstetric care facilities (excluding abortions) were analysed. Facility childbirth constituted 81% of expected births in urban and 16% in rural areas. Based on the reference estimate that 1.4% of childbearing women were expected to need major obstetric intervention, unmet obstetric need was 77 of 106 women, thus 73% (95% CI 71-75%) in rural areas whereas urban areas had no deficit. Major obstetric interventions for absolute maternal indications were higher in urban 2.1% (95% CI 1.60-2.71%) than in rural areas 0.4% (95% CI 0.27-0.55%), with an urban to rural rate ratio of 5.5 (95% CI 3.55-8.76). CONCLUSIONS: Women in rural areas had deficient obstetric care. The likelihood of under-going a life-saving intervention was 5.5 times higher for women in urban than rural areas. Targeting rural women with life saving services could substantially reduce this inequity and preventable deaths. PMID- 26824600 TI - Phenotypic and Molecular Aspects of Staphylococcus spp. Isolated from Hospitalized Patients and Beef in the Brazilian Amazon. AB - The aim of this study was to characterize and compare Staphylococcus spp. isolated from hospitalized patients and beef marketed in the city of Porto Velho RO, Brazil. The isolates were subjected to antibiogram tests, adherence capacity tests, detection of the mecA gene, and epidemiological investigation by the random amplified polymorphic DNA (RAPD) technique, using the primers M13 and H12. Among the 123 Staphylococcus spp. isolates, 50 were identified as S. aureus and 73 as coagulase-negative Staphylococcus; among the latter, 7 species were identified. It was observed that the coagulase-negative Staphylococcus isolates showed greater adhesion ability than S. aureus. The profile of antimicrobial susceptibility was different among isolates, all of which were susceptible to vancomycin and linezolid, and had high penicillin resistance rates, varying according to the bacterial class and the source. In this study, all strains were negative for mecA gene detection; however, 36% of S. aureus and 17% of coagulase negative Staphylococcus were resistant to oxacillin. The genetic relationship of these bacteria, analyzed by RAPD, was able to discriminate the species of coagulase-negative Staphylococcus strains of S. aureus along its origin. It was concluded that the isolates of Staphylococcus spp. derived from beef and human infections differ genetically. Thus, it is suggested that isolates from beef, which were grouped within hospital isolates, were probably carried via contact with beef in hospital professionals or patients. PMID- 26824601 TI - Lethal and Sublethal Toxicity Comparison of BFRs to Three Marine Planktonic Copepods: Effects on Survival, Metabolism and Ingestion. AB - The estuarine planktonic copepods have a wide geographical distribution and commendable tolerance to various kinds of contaminants. The primary aim of the present study was to contrast the impacts of model POPs (TBBPA and HBCD) on three common estuarine planktonic copepods (Oithona similis, Acartia pacifica and Pseudodiaptomus inopinus) and establish a protocol for the assessment of acute toxicity of marine organic pollutants. We first quantified the 96h-LC50 (0.566, 0.04 and 0.257 mg/L of TBBPA to the three subjects above respectively and 0.314 mg/L of HBCD to P. inopinus; all reported concentrations are nominal values). In the sub-lethal toxicity tests, it was turned out that the effects of copepods exposed to TBBPA could product different influences on the energy ingestion and metabolism. Different type of pollutions, meanwhile, could also bring varying degree effect on the target copepods. In general, the indicators (the rate of oxygen consumption, ammonia excretion, food ingestion and filtration) in higher concentration groups showed marked significant difference compared with controls as well a dose-effect relationship. The study also extended the research on the joint toxicity of TBBPA and HBCD based on the survival rate of P.inopinus. Whether 1:1 concentration or 1:1 toxic level, the research showed synergy effect relative to single exposure conditions. The result indicated that current single ecological testing used for environmental protection activities may underestimate the risk for copepods. It was also demonstrated that short-term sub-lethal experiment could be a standard to evaluate the sensitivity of copepods to POPs. PMID- 26824602 TI - Anatomical and Physiological Changes after Paclitaxel-Coated Balloon for Atherosclerotic De Novo Coronary Lesions: Serial IVUS-VH and FFR Study. AB - AIMS: To assess the serial changes of de novo coronary lesions treated with paclitaxel-coated balloon (PCB) using intravascular ultrasound virtual histology (IVUS-VH) and fractional flow reserve (FFR). METHOD AND RESULTS: This prospective observational study enrolled 27 patients with coronary artery disease treated with PCB who underwent coronary angiography, IVUS-VH and FFR before, immediately after intervention and at 9 months. 28 de novo lesions were successfully treated with PCB. Angiographic late luminal loss was 0.02 +/- 0.27 mm. Mean vessel and lumen areas showed increase at 9 months (12.0 +/- 3.5 mm(2) to 13.2 +/- 3.9 mm(2), p <0.001; and 5.4 +/- 1.2 mm(2) to 6.5 +/- 1.8 mm(2), p <0.001, respectively). Although mean plaque area was unchanged (6.6 +/- 2.6 mm2 to 6.6 +/ 2.4 mm(2), p = 0.269), percent atheroma volume decreased significantly (53.4 +/- 7.9% to 49.5 +/- 6.4%, p = 0.002). The proportion of plaque compositions including fibrous, fibrofatty, dense calcium and necrotic core by IVUS-VH was unchanged at 9 months. The FFR of the treated lesion was 0.71 +/- 0.13 pre procedure, 0.87 +/- 0.06 post-procedure and 0.84 +/- 0.06 at follow-up. CONCLUSIONS: De novo coronary lesions treated with PCB showed persistent anatomical and physiological patency with plaque redistribution and vessel remodeling without chronic elastic recoil or plaque compositional change during follow-up. PMID- 26824603 TI - Co-calibrating quality-of-life scores from three pulmonary disorders: implications for comparative-effectiveness research. AB - Background Efficient use of health resources requires accurate outcome assessment. Disease-specific patient-reported outcome (PRO) measures are designed to be highly relevant to patients with a specific disease. They have advantages over generic PROs that lack relevance to patient groups and miss crucial impacts of illness. It is thought that disease-specific measurement cannot be used in comparative effectiveness research (CER). The present study provides further evidence of the value of disease-specific measures in making valid comparisons across diseases. Methods The Asthma Life Impact Scale (ALIS, 22 items), Living with Chronic Obstructive Pulmonary Disease (LCOPD, 22 items) scale, and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR, 25 items) were completed by 140, 162, and 91 patients, respectively. The three samples were analyzed for fit to the Rasch model, then combined into a scale consisting of 58 unique items and re analyzed. Raw scores on the three measures were co-calibrated and a transformation table produced. Results The scales fit the Rasch model individually (ALIS Chi(2) probability value (p-Chi(2)) = 0.05; LCOPD p-Chi(2 )=( )0.38; CAMPHOR p-Chi(2 )=( )0.92). The combined data also fit the Rasch model (p Chi(2 )=( )0.22). There was no differential item functioning related to age, gender, or disease. The co-calibrated scales successfully distinguished between perceived severity groups (p < 0.001). Limitations The samples were drawn from different sources. For scales to be co-calibrated using a common item design, they must be based on the same theoretical construct, be unidimensional, and have overlapping items. Conclusions The results showed that it is possible to co calibrate scores from disease-specific PRO measures. This will permit more accurate and sensitive outcome measurement to be incorporated into CER. The co calibration of needs-based disease-specific measures allows the calculation of gamma scores that can be used to compare directly the impact of any type of interventions on any diseases included in the co-calibration. PMID- 26824604 TI - Aberrations Involving Chromosome 1 as a Possible Predictor of Odds Ratio for Colon Cancer--Results from the Krakow Case-Control Study. AB - BACKGROUND: There is still an open question how to predict colorectal cancer risk before any morphological changes appear in the colon. OBJECTIVE: The purpose was to investigate aberrations in chromosomes 1, 2 and 4 in peripheral blood lymphocytes analyzed by fluorescence in situ hybridization technique as a tool to assess the likelihood of colorectal cancer. METHODS: A hospital-based case control study included 20 colon cancer patients and 18 hospital-based controls. Information about potential covariates was collected by interview. The frequency of stable and unstable chromosome aberrations in chromosome 1, 2 and 4 was assessed by fluorescence in situ hybridization technique. RESULTS: Colorectal cancer patients, as compared to controls, had a relatively higher frequency of chromosome 1 translocations (median: 3.5 versus 1.0 /1000 cells, p = 0.006), stable aberrations (3.8 versus 1.0 /1000 cells, p = 0.007) and total aberrations (p = 0.009). There were no differences observed for chromosomes 2 and 4. Our results showed an increase in the odds of having colon cancer by about 50-80% associated with an increase by 1/1000 cells in the number of chromosome 1 aberrations. CONCLUSIONS: The results revealed that the frequency of chromosomal aberrations, especially translocations in chromosome 1, seems to be a promising method to show a colon cancer risk. Additionally, our study suggests the reasonableness of use of biomarkers such as chromosome 1 aberrations in peripheral blood lymphocytes in screening prevention programs for individuals at higher colon cancer risk to identify those who are at increased risk and require more frequent investigations, e.g. by sigmoidoscopy. PMID- 26824605 TI - Correlation between Ribosome Biogenesis and the Magnitude of Hypertrophy in Overloaded Skeletal Muscle. AB - External loads applied to skeletal muscle cause increases in the protein translation rate, which leads to muscle hypertrophy. Although some studies have demonstrated that increases in the capacity and efficiency of translation are involved in this process, it remains unclear how these two factors are related to the magnitude of muscle hypertrophy. The present study aimed to clarify the roles played by the capacity and efficiency of translation in muscle hypertrophy. We used an improved synergist ablation in which the magnitude of compensatory hypertrophy could be controlled by partial removal of synergist muscles. Male rats were assigned to four groups in which the plantaris muscle was unilaterally subjected to weak (WK), moderate (MO), middle (MI), and strong (ST) overloading by four types of synergist ablation. Fourteen days after surgery, the weight of the plantaris muscle per body weight increased by 8%, 22%, 32% and 45%, in the WK, MO, MI and ST groups, respectively. Five days after surgery, 18+28S rRNA content (an indicator of translational capacity) increased with increasing overload, with increases of 1.8-fold (MO), 2.2-fold (MI), and 2.5-fold (ST), respectively, relative to non-overloaded muscle (NL) in the WK group. rRNA content showed a strong correlation with relative muscle weight measured 14 days after surgery (r = 0.98). The phosphorylated form of p70S6K (a positive regulator of translational efficiency) showed a marked increase in the MO group, but no further increase was observed with further increase in overload (increases of 22.6-fold (MO), 17.4-fold (MI), and 18.2-fold (ST), respectively, relative to NL in the WK group). These results indicate that increases in ribosome biogenesis at the early phase of overloading are strongly dependent on the amount of overloading, and may play an important role in increasing the translational capacity for further gain of muscular size. PMID- 26824606 TI - Melatonin Signaling Controls the Daily Rhythm in Blood Glucose Levels Independent of Peripheral Clocks. AB - Melatonin is rhythmically secreted by both the pineal gland and retina in a circadian fashion, with its peak synthesis occurring during the night. Once synthesized, melatonin exerts its effects by binding to two specific G-protein coupled receptors-melatonin receptor type 1(MT1) and melatonin receptor type 2(MT2). Recent studies suggest the involvement of MT1 and MT2 in the regulation of glucose homeostasis; however the ability of melatonin signaling to impart timing cues on glucose metabolism remains poorly understood. Here we report that the removal of MT1 or MT2 in mice abolishes the daily rhythm in blood glucose levels. Interestingly, removal of melatonin receptors produced small effects on the rhythmic expression patterns of clock genes within skeletal muscle, liver, and adipose tissue. Taken together, our data suggest that the loss of the daily rhythm in blood glucose observed in MT1(-/-) and MT2(-/-) mice does not occur as a consequence of 'disrupted' clocks within insulin sensitive tissues. Finally our results highlight a diurnal contribution of melatonin receptor signaling in the daily regulation of blood glucose levels. PMID- 26824608 TI - Urine/Plasma Neutrophil Gelatinase Associated Lipocalin Ratio Is a Sensitive and Specific Marker of Subclinical Acute Kidney Injury in Mice. AB - BACKGROUND: Detection of acute kidney injury (AKI) is still a challenge if conventional markers of kidney function are within reference range. We studied the sensitivity and specificity of NGAL as an AKI marker at different degrees of renal ischemia. METHODS: Male C57BL/6J mice were subjected to 10-, 20- or 30-min unilateral renal ischemia, to control operation or no operation, and AKI was evaluated 1 day later by histology, immunohistochemistry, BUN, creatinine, NGAL (plasma and urine) and renal NGAL mRNA expression. RESULTS: A short (10-min) ischemia did not alter BUN or kidney histology, but elevated plasma and urinary NGAL level and renal NGAL mRNA expression although to a much smaller extent than longer ischemia. Surprisingly, control operation elevated plasma NGAL and renal NGAL mRNA expression to a similar extent as 10-min ischemia. Further, the ratio of urine to plasma NGAL was the best parameter to differentiate a 10-min ischemic injury from control operation, while it was similar in the non and control operated groups. CONCLUSIONS: These results suggest that urinary NGAL excretion and especially ratio of urine to plasma NGAL are sensitive and specific markers of subclinical acute kidney injury in mice. PMID- 26824607 TI - Natural Pig Plasma Immunoglobulins Have Anti-Bacterial Effects: Potential for Use as Feed Supplement for Treatment of Intestinal Infections in Pigs. AB - There is an increasing demand for non-antibiotics solutions to control infectious disease in intensive pig production. Here, one such alternative, namely pig antibodies purified from slaughterhouse blood was investigated in order to elucidate its potential usability to control post-weaning diarrhoea (PWD), which is one of the top indications for antibiotics usage in the pig production. A very cost-efficient and rapid one-step expanded bed adsorption (EBA) chromatography procedure was used to purify pig immunoglobulin G from slaughterhouse pig plasma (more than 100 litres), resulting in >85% pure pig IgG (ppIgG). The ppIgG thus comprised natural pig immunoglobulins and was subsequently shown to contain activity towards four pig-relevant bacterial strains (three different types of Escherichia coli and one type of Salmonella enterica) but not towards a fish pathogen (Yersinia ruckeri), and was demonstrated to inhibit the binding of the four pig relevant bacteria to a pig intestinal cell line (IPEC-J2). Finally it was demonstrated in an in vivo weaning piglet model for intestinal colonization with an E. coli F4+ challenge strain that ppIgG given in the feed significantly reduced shedding of the challenge strain, reduced the proportion of the bacterial family Enterobacteriaceae, increased the proportion of families Enterococcoceae and Streptococcaceae and generally increased ileal microbiota diversity. Conclusively, our data support the idea that natural IgG directly purified from pig plasma and given as a feed supplement can be used in modern swine production as an efficient and cost-effective means for reducing both occurrence of PWD and antibiotics usage and with a potential for the prevention and treatment of other intestinal infectious diseases even if the causative agent might not be known. PMID- 26824609 TI - Transcriptional Analysis of T Cells Resident in Human Skin. AB - Human skin contains various populations of memory T cells in permanent residence and in transit. Arguably, the best characterized of the skin subsets are the CD8(+) permanently resident memory T cells (TRM) expressing the integrin subunit, CD103. In order to investigate the remaining skin T cells, we isolated skin tropic (CLA(+)) helper T cells, regulatory T cells, and CD8(+) CD103(-) T cells from skin and blood for RNA microarray analysis to compare the transcriptional profiles of these groups. We found that despite their common tropism, the T cells isolated from skin were transcriptionally distinct from blood-derived CLA(+) T cells. A shared pool of genes contributed to the skin/blood discrepancy, with substantial overlap in differentially expressed genes between each T cell subset. Gene set enrichment analysis further showed that the differential gene profiles of each human skin T cell subset were significantly enriched for previously identified TRM core signature genes. Our results support the hypothesis that human skin may contain additional TRM or TRM-like populations. PMID- 26824612 TI - Synthesis of Oligo(thienylene-vinylene) by Regiocontrolled Deprotonative Cross Coupling. AB - Concise synthesis of oligo(thienylene-vinylene) with a head-to-tail type structure is achieved by regioselective deprotonative coupling of 3 hexylthiophene. The palladium catalyzed reaction of 3-hexylthiophene with (E)-2 (2-bromoethenyl)-3-hexylthiophene takes place to afford head-to-tail type trans 1,2-dithienylethene. Further extension of a vinylthiophene unit is similarly performed in an iterative manner. PMID- 26824613 TI - Changes of volatile sulphur compounds during therapy of a case series of patients with chronic periodontitis and halitosis. AB - AIM: To assess the effect of different stages of intervention on volatile sulphur compounds (VSCs) of periodontitis patients with halitosis, before and after non surgical periodontal therapy. MATERIAL & METHODS: This clinical trial included 18 adults with chronic periodontitis and halitosis. After initial examination, patients received oral hygiene (OH) instructions and tongue cleaner. One week later, non-surgical periodontal therapy was completed within 48 h. Measurements were at baseline, 1 week after OH, 1 and 6 weeks post therapy. These included simplified plaque index (sPlI), probing pocket depth (PPD), bleeding on probing (BoP), Winkel Tongue Coating Index (WTCI), organoleptic scores (OLSs) of nose and mouth air and VSCs. RESULTS: sPlI, BoP, WTCI, OLS of the mouth air and VSCs showed significant differences (p < 0.05), even after 1 week of OH. A further significant decrease was determined 1 week after non-surgical therapy for WTCI, OLS (nose and mouth air) and methyl mercaptan concentration. A significant decrease, 6 weeks post therapy, was observed for sPlI, BoP, WTCI, PPD, OLS of the nose and mouth air and VSCs (p < 0.05). CONCLUSIONS: Oral hygiene and tongue cleaning improve the OLSs of the mouth air and reduce VSCs. Periodontal therapy further improves the OLSs and reduces the concentration of VSCs. PMID- 26824611 TI - The Development and Validation of the Indian Family Violence and Control Scale. AB - The high prevalence of domestic violence (DV) among married women in India and associated negative health repercussions highlight the need for effective prevention strategies and tools to measure the efficacy of such interventions. Literature supporting differing manifestations of DV by culture underscores the need for a culturally-tailored scale to more effectively measure DV in the Indian context. We therefore aimed to develop and validate such a tool, the Indian Family Violence and Control Scale (IFVCS), through a mixed-methods study. The psychometric development of IFVCS is herein discussed. After field pre-testing and expert review, a 63-item questionnaire was administered to a random sample of 630 married women from May-July 2013 in Pune, India. The item response theory approach for binary data to explore the IFVCS structure suggested that IFVCS is reliable, with the majority of items having high (>0.5) and significant factor loadings. Concurrent validity, assessed by comparing responses to IFVCS with the validated, abridged Conflict Tactics Scale-2, was high (r = 0.899, p<0.001) as was the construct validity, demonstrated by its significant association with several established DV correlates. Therefore, initial assessment of the IFVCS psychometric properties suggests that it is an effective tool for measuring DV among married women in India and speaks to its capacity for enhancing understanding of DV epidemiology and for evaluating the effectiveness of future DV interventions. PMID- 26824614 TI - Multispecies Biofilms Transform Selenium Oxyanions into Elemental Selenium Particles: Studies Using Combined Synchrotron X-ray Fluorescence Imaging and Scanning Transmission X-ray Microscopy. AB - Selenium (Se) is an element of growing environmental concern, because low aqueous concentrations can lead to biomagnification through the aquatic food web. Biofilms, naturally occurring microbial consortia, play numerous important roles in the environment, especially in biogeochemical cycling of toxic elements in aquatic systems. The complexity of naturally forming multispecies biofilms presents challenges for characterization because conventional microscopic techniques require chemical and physical modifications of the sample. Here, multispecies biofilms biotransforming selenium oxyanions were characterized using X-ray fluorescence imaging (XFI) and scanning transmission X-ray microscopy (STXM). These complementary synchrotron techniques required minimal sample preparation and were applied correlatively to the same biofilm areas. Sub micrometer XFI showed distributions of Se and endogenous metals, while Se K-edge X-ray absorption spectroscopy indicated the presence of elemental Se (Se0). Nanoscale carbon K-edge STXM revealed the distributions of microbial cells, extracellular polymeric substances (EPS), and lipids using the protein, saccharide, and lipid signatures, respectively, together with highly localized Se0 using the Se LIII edge. Transmission electron microscopy showed the electron dense particle diameter to be 50-700 nm, suggesting Se0 nanoparticles. The intimate association of Se0 particles with protein and polysaccharide biofilm components has implications for the bioavailability of selenium in the environment. PMID- 26824610 TI - K+ Channel Inhibition Differentially Regulates Migration of Intestinal Epithelial Cells in Inflamed vs. Non-Inflamed Conditions in a PI3K/Akt-Mediated Manner. AB - BACKGROUND: Potassium channels have been shown to determine wound healing in different tissues, but their role in intestinal epithelial restitution--the rapid closure of superficial wounds by intestinal epithelial cells (IEC)--remains unclear. METHODS: In this study, the regulation of IEC migration by potassium channel modulation was explored with and without additional epidermal growth factor (EGF) under baseline and interferon-gamma (IFN-gamma)-pretreated conditions in scratch assays and Boyden chamber assays using the intestinal epithelial cell lines IEC-18 and HT-29. To identify possibly involved subcellular pathways, Western Blot (WB)-analysis of ERK and Akt phosphorylation was conducted and PI3K and ERK inhibitors were used in scratch assays. Furthermore, mRNA-levels of the potassium channel KCNN4 were determined in IEC from patients suffering from inflammatory bowel diseases (IBD). RESULTS: Inhibition of Ca(2+)-dependent potassium channels significantly increased intestinal epithelial restitution, which could not be further promoted by additional EGF. In contrast, inhibition of KCNN4 after pretreatment with IFN-gamma led to decreased or unaffected migration. This effect was abolished by EGF. Changes in Akt, but not in ERK phosphorylation strongly correlated with these findings and PI3K but not ERK inhibition abrogated the effect of KCNN4 inhibition. Levels of KCNN4 mRNA were higher in samples from IBD patients compared with controls. CONCLUSIONS: Taken together, we demonstrate that inhibition of KCNN4 differentially regulates IEC migration in IFN-gamma pretreated vs. non pretreated conditions. Moreover, our data propose that the PI3K signaling cascade is responsible for this differential regulation. Therefore, we present a cellular model that contributes new aspects to epithelial barrier dysfunction in chronic intestinal inflammation, resulting in propagation of inflammation and symptoms like ulcers or diarrhea. PMID- 26824615 TI - Wetting of Hydrophilic Electrospun Mats Produced by Blending SEBS with PEO-PPO PEO Copolymers of Different Molecular Weight. AB - The interaction of electrospun mats with water is critical for many possible applications, and the water contact angle on the surface is the parameter usually measured to characterize wetting. Although useful for hydrophobic surfaces, this approach is limited for hydrophilic mats, where wicking also has to be considered. In this case, it is still unclear how the fiber surface chemical composition and morphology will affect the wetting behavior of electrospun mats. In this work, wetting was studied with different hydrophilic membranes produced by blending thermoplastic elastomer poly(styrene)-b-poly(ethylene-butylene)-b poly(styrene) (SEBS) with amphiphilic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO) molecules. Three different types of PEO-PPO-PEO, with different molar masses, PEO content, and physical form were used. The effect of these differences on the wetting behavior of the electrospun mats was evaluated by contact angle goniometry, wicking measurements, and different imaging techniques. X-ray photoelectron spectroscopy was used to characterize the surface chemical composition. The smaller molecules quickly saturated the surface at low concentrations, making the mats hydrophilic. The sheath of PEO-PPO-PEO also resulted in fast absorption of water, when comparing the saturated and nonsaturated surfaces. Longer PEO chain-ends seemed to hinder complete segregation and also led to a higher activation time when in contact with water. Liquid PEO-PPO-PEO was easily leached by water. PMID- 26824616 TI - First-Principles Density Functional Theory Modeling of Li Binding: Thermodynamics and Redox Properties of Quinone Derivatives for Lithium-Ion Batteries. AB - The Li-binding thermodynamics and redox potentials of seven different quinone derivatives are investigated to determine their suitability as positive electrode materials for lithium-ion batteries. First, using density functional theory (DFT) calculations on the interactions between the quinone derivatives and Li atoms, we find that the Li atoms primarily bind with the carbonyl groups in the test molecules. Next, we observed that the redox properties of the quinone derivatives can be tuned in the desired direction by systematically modifying their chemical structures using electron-withdrawing functional groups. Further, DFT-based investigations of the redox potentials of the Li-bound quinone derivatives provide insights regarding the changes induced in their redox properties during the discharging process. The redox potential decreases as the number of bound Li atoms is increased. However, we found that the functionalization of the quinone derivatives with carboxylic acids can improve their redox potential as well as their charge capacity. Through this study, we also determined that the cathodic activity of quinone derivatives during the discharging process relies strongly on the solvation effect as well as on the number of carbonyl groups available for further Li binding. PMID- 26824617 TI - Correction: Developing and Integrating Advanced Movement Features Improves Automated Classification of Ciliate Species. PMID- 26824618 TI - Organic Amine-Mediated Synthesis of Polymer and Carbon Microspheres: Mechanism Insight and Energy-Related Applications. AB - A general organic amine-mediated synthesis of polymer microspheres is developed based on the copolymerization of resorcinol, formaldehyde, and various organic amines at room temperature. Structure formation and evolution of colloidal microspheres in the presence of polyethylenimine are monitored by dynamic light scattering measurements. It is found that the colloidal clusters are formed instantaneously and then experience an anomalous shrinkage-growth process. This should be caused by two different reaction pathways: cross-linking inside the microspheres and step-growth polymerization of substituted resorcinol on the microsphere surface, leading to the formation of core-shell heterogeneous structures as confirmed by TEM observation and XPS analysis. A formation mechanism of polymer microspheres is provided based on the aggregation of polyethylenimine/resorcinol-formaldehyde (PEI-RF) self-assembled nuclei, which is apparently different from the conventional Stober process. Furthermore, nitrogen doped carbon microspheres are prepared by the direct carbonization of these polymer microspheres, which exhibit microporous BET surface areas of 400-500 m(2) g(-1), high nitrogen contents of 5-6 wt %, and a good CO2 adsorption capacity up to 3.6 mmol g(-1) at 0 degrees C. KOH activation is further employed to develop the porous texture of carbon microspheres without sacrificing the spherical morphology. The resultant activated carbon microspheres exhibit small particle size (<80 nm), high BET surface areas of 1500-2000 m(2) g(-1), and considerable nitrogen content of 2.2-2.0 wt %. When used as the electrode materials for supercapacitors, these activated carbon microspheres demonstrate a high capacitance up to 240 F g(-1), an unprecedented rate performance and good cycling performance. PMID- 26824619 TI - Distributive and Quantitative Analysis of the Main Active Saponins in Panax notoginseng by UHPLC-QTOF/MS Combining with Fluorescence Microscopy and Laser Microdissection. AB - The distribution of the secondary metabolites in different tissues of Panax notoginseng has not yet been investigated. Furthermore, there is no scientific evidence available for the quality assessment of P. notoginseng. This is the first study on the tissue-specific chemicals to identify and determinate the main secondary metabolite profiling of P. notoginseng in order to provide more information for quality evaluation. In this study, the ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry approach combined with fluorescence microscopy and laser microdissection was developed and validated for distributive and quantitative analyses of the main active saponins of different tissues from P. notoginseng. The results showed that the total content of notoginsenoside R1, ginsenoside Rg1, ginsenoside Rb1, and ginsenoside Rd in the xylem were higher than those in the cork, phloem, and cortex. There was no significant difference in the distribution of saponins between the main roots and the branch roots of the fresh unprocessed materials, nor was there a significant difference in their distribution between the main roots from the fresh unprocessed vs. the dried processed commercial materials. This method illustrated the distribution pattern of the main saponins in the tissues of P. notoginseng, which could help to explain the relationship between its anatomical structures, morphological characteristics, and quality. In summary, this study has significance for the procurement, collection, cultivation, effective management, and quality control of P. notoginseng. PMID- 26824620 TI - Effect of the Hydroethanolic Extract from Echinodorus grandiflorus Leaves and a Fraction Enriched in Flavone-C-Glycosides on Antigen-Induced Arthritis in Mice. AB - The leaves of Echinodorus grandiflorus are traditionally used in Brazil to treat several inflammatory conditions, including arthritis. This study aimed to investigate the antiarthritis activity of the 70% ethanol extract of E. grandiflorus leaves and a standardized flavonoid-rich fraction in an antigen induced arthritis model in mice. Previously immunized mice were treated per os with saline (control group), 70% ethanol extract (100-1000 mg/kg), or a flavonoid rich fraction (0.7-7.2 mg/kg) 40 minutes before and 3 and 6 hours after the challenge with antigen into the knee joint. The administration of the 70% ethanol extract and flavonoid-rich fraction to mice significantly reduced neutrophil recruitment to the joint cavity and in periarticular tissue. The levels of chemokine (C-X-C motif) ligand 1, tumor necrosis factor-alpha, and interleukin 1beta quantified by the enzyme-linked immunosorbent assay (ELISA) in the periarticular tissue were also diminished in mice treated with the 70% ethanol extract and flavonoid-rich fraction, as well as mechanical hypernociception. Histological analysis confirmed that both the 70% ethanol extract and flavonoid rich fraction suppressed joint inflammation and inhibited cartilage and bone destruction when compared to the control group. Our results demonstrate, for the first time, that E. grandiflorus has anti-inflammatory activity in an experimental arthritis model and highlights the role of flavonoids in the observed response. PMID- 26824621 TI - Danggui Buxue Tang, Chinese Herbal Decoction Containing Astragali Radix and Angelicae Sinensis Radix, Induces Production of Nitric Oxide in Endothelial Cells: Signaling Mediated by Phosphorylation of Endothelial Nitric Oxide Synthase. AB - Danggui Buxue Tang, an ancient Chinese herbal decoction containing Astragali Radix and Angelicae Sinensis Radix at the weight ratio of 5:1, is used to mitigate menopausal syndromes in women. The pharmacological properties of Danggui Buxue Tang have been illustrated in bone development, blood enhancement, and immune stimulation. Here, we extended the possible pharmacological role of Danggui Buxue Tang in cardiovascular function. In cultured human umbilical vein endothelial cells, the application of Danggui Buxue Tang induced the release of nitric oxide and the phosphorylation of endothelial nitric oxide synthase and Akt kinase in time- and dose-dependent manners. The robust activation of nitric oxide signaling, however, required the boiling of Astragali Radix and Angelicae Sinensis Radix together, i.e., as Danggui Buxue Tang instead of other herbal extracts. The Danggui Buxue Tang-induced phosphorylation of endothelial nitric oxide synthase and Akt kinase in human umbilical vein endothelial cells were fully blocked by treatment with an endothelial nitric oxide synthase inhibitor (L NAME), a PI3K/Akt inhibitor (LY294002), and a Ca(2+) chelator (BAPTA-AM). In parallel, the blockage of endothelial nitric oxide synthase and Akt activation subsequently fully abolished the Danggui Buxue Tang-induced nitric oxide production. PMID- 26824622 TI - Development of an Enzyme-Linked Immunosorbent Assay and Immunoaffinity Column Chromatography for Saikosaponin d Using an Anti-Saikosaponin d Monoclonal Antibody. AB - This work developed a novel immunochemical approach for the quality control of saikosaponin d using an enzyme-linked immunosorbent assay. Splenocytes from mice immunized with the saikosaponin d-bovine serum albumin conjugate were fused with the hypoxanthine-aminopterin-thymidine-sensitive mouse myeloma SP2/0 cell line, and a hybridoma secreting monoclonal antibody against saikosaponin d was successfully obtained. The prepared anti-saikosaponin d monoclonal antibody 1E7F3 has a novel characteristic, showing weak reactivity with compounds that are structurally related to saikosaponin d. Using monoclonal antibody 1E7F3, a specific and reliable enzyme-linked immunosorbent assay was developed to detect saikosaponin d. The system shows a full measurement range from 156.25 to 5000.00 ng * mL(-1). Both intra-assay and inter-assay repeatability and precision were achieved, with relative standard deviations lower than 10.00%. The recovery rates ranged from 92.36% to 101.00%, meeting the requirements for biological samples. There was a good correlation between the enzyme-linked immunosorbent assay and high-performance liquid chromatography analyses of saikosaponin d, and the saikosaponin d levels in formulated Chinese medicines were successfully determined. Furthermore, immunoaffinity column chromatography was established using this anti-saikosaponin d monoclonal antibody, and the elution profile of saikosaponin d was detected by a Bio-Rad QuadTec UV/Vis detector at 203 nm. The results demonstrate that we generated a reliable and more efficient assay system for measuring saikosaponin d and provide a potential approach for purifying and separating saikosaponin d. PMID- 26824623 TI - Beneficial Effects of a Flavonoid Fraction of Herba Epimedii on Bone Metabolism in Ovariectomized Rats. AB - A flavonoid fraction of Herba Epimedii, including eight flavonoid glycoside compounds, epimedoside A, ikarisoside F, baohuoside II, sagittatoside A, sagittatoside B, 7-O-rhamnosyl icariside II, 2"-O-rhamnosyl icariside II, and baohuoside I, was isolated and prepared from the leaves of Herba Epimedii. This study was conducted to assess the potential effect of the flavonoid fraction of Herba Epimedii on osteoporosis in ovariectomized rats. Rats received repeated administration of a vehicle (ovariectomized), the flavonoid fraction of Herba Epimedii (7.5, 15, 30 mg/kg/d), and ipriflavone (200 mg/kg/d) once a day for 8 weeks, beginning 4 weeks after ovariectomization. Then, the bone turnover markers, bone biomechanical properties, trabecular architecture, and related protein expressions were evaluated by biochemical assay kits, mechanical testing, microcomputed tomography, immunohistochemical evaluation, and Western blot analysis. Treatment with the flavonoid fraction of Herba Epimedii (15, 30 mg/kg/d) and ipriflavone (200 mg/kg/d) significantly increased bone strength while dramatically inhibiting the serum alkaline phosphatase and tartrate resistant acid phosphatase levels in ovariectomized rats. Furthermore, the flavonoid fraction of Herba Epimedii also increased osteoprotegerin protein expression and reduced the receptor activator of nuclear factor-kappaB ligand protein expression compared with ovariectomized rats. In addition, the microcomputed tomography results showed that the flavonoid fraction of Herba Epimedii treatment significantly improved trabecular bone mineral density and restored the bone microarchitecture in ovariectomized rats. Therefore, our results indicated that the flavonoid fraction of Herba Epimedii might be beneficial for improving postmenopausal osteoporosis and should be considered as a promising candidate for treating postmenopausal osteoporosis. PMID- 26824624 TI - Antiviral and Cytotoxic Isocoumarin Derivatives from an Endophytic Fungus Aspergillus oryzae. AB - Oryzaeins A-D (1-4), four new isocoumarin derivatives, along with five known ones (5-9) were isolated from solid cultures of an endophytic fungus Aspergillus oryzae. Their structures were elucidated by detailed spectroscopic analysis and by comparison with reported data of related derivatives. Among them, compounds 1 and 2 represent the first examples of isocoumarins possessing an unusual 2 oxopropyl group and a rare 3-hydroxypropyl group. Compounds 1 and 2 displayed moderate anti-tobacco mosaic virus activities with inhibition rates of 28.4% and 30.6%, respectively, at the concentration of 20 uM. The new compounds showed moderate inhibitory activities against several human tumor cell lines with IC50 values in the range of 2.8-8.8 uM. Supporting information available online at http://www.thieme-connect.de/products. PMID- 26824625 TI - Zika Virus: Emergence and Emergency. PMID- 26824626 TI - Recent progress and challenges of organometal halide perovskite solar cells. AB - We review recent progress in the development of organometal halide perovskite solar cells. We discuss different compounds used to construct perovskite photoactive layers, as well as the optoelectronic properties of this system. The factors that affect the morphology of the perovskite active layer are explored, e.g. material composition, film deposition methods, casting solvent and various post-treatments. Different strategies are reviewed that have recently emerged to prepare high performing perovskite films, creating polycrystalline films having either large or small grain size. Devices that are constructed using meso superstructured and planar architectures are summarized and the impact of the fabrication process on operational efficiency is discussed. Finally, important research challenges (hysteresis, thermal and moisture instability, mechanical flexibility, as well as the development of lead-free materials) in the development of perovskite solar cells are outlined and their potential solutions are discussed. PMID- 26824627 TI - Reply. PMID- 26824628 TI - Increased C-reactive protein and fever in Japanese infants with food protein induced enterocolitis syndrome. AB - BACKGROUND: Increased C-reactive protein (CRP) and fever are observed in some infants with food protein-induced enterocolitis syndrome (FPIES) in Japan, but the reproducibility of these findings has not yet been confirmed on oral food challenge (OFC). METHODS: Fourteen infants with FPIES induced by cow's milk (CM) formula were enrolled. OFC using CM formula was performed on each infant once or repeatedly (total 18 tests), with a stepwise incremental protocol in an infection controlled setting. CRP was measured 24 h after the last ingestion of the CM formula. RESULTS: Increased CRP was observed in 11 of the 18 OFC conducted (median, 2.60 mg/dL; range, 0.22-4.84 mg/dL). Fever was induced in six occasions during OFC. Serum CRP in the patients with fever increased to median 3.76 mg/dL (range, <0.7-4.84 mg/dL), which was significantly higher than that of the patients without fever (median <0.1 mg/dL; range, <0.1-2.6 mg/dL; P < 0.001). CRP during OFC significantly correlated with that at disease onset (rs = 0.62, P < 0.02). Three of the four patients with fever at disease onset also had fever during OFC. CONCLUSIONS: Increased CRP and fever are reproducible during OFC in some infants with FPIES, suggesting that these are not accidental phenomena, but instead are associated with FPIES itself in Japanese patients. PMID- 26824629 TI - Symptom Frequency, Intensity, and Distress in Patients with Lower Limb Lymphedema. AB - BACKGROUND: Patients with lower limb lymphedema experience symptoms of pain, swelling, tightness, and heaviness in their legs. Less is known of the intensity and distress associated with these symptoms. This study sought to identify and compare the symptoms and the level of intensity and distress associated with symptoms by type of lymphatic disruption. METHODS AND RESULTS: A cross-sectional design was used. Patients completed an online survey that included: a demographic form, the Lymphedema Symptom Intensity and Distress Survey-Leg, and an open-ended question. The most prevalent symptoms were swelling, concerns about looks, heaviness, tightness, fatigue, and reduced physical activity. Statistically significant differences were found among groups in coldness in legs (chi(2) (df=3) = 9.0, p = 0.03), lack of confidence in self (chi(2) (df=3) = 10.6, p = 0.014), and feeling less sexually attractive (chi(2) (df=6) = 12.6, p = 0.049). Group differences were also observed in the intensity of heaviness (chi(2) (df=3) = 9.11, p = 0.03), numbness, (chi(2) (df=3) = 10.66, p = 0.014), achiness (chi(2) (df=3) = 12.40, p = 0.006), skin flakiness (chi(2) (df=3) = 13.22, p = 0.004), and lack of interest in sex (chi(2) (df=3) = 8.95, p = 0.030). Statistically significant group differences were not found in distress related to symptoms. CONCLUSIONS: Despite the number of symptoms reported by patients with lower-limb lymphedema, only a few statistically significant differences in symptoms and level of intensity were observed by type of lymphatic disruption. No statistically significant group differences were found in the distress level associated with any of the symptoms. PMID- 26824630 TI - Editorial Comment for Chehab et al. PMID- 26824631 TI - Platelet activation and cardiovascular comorbidities in patients with chronic obstructive pulmonary disease. AB - Objective Platelet activation in COPD patients is associated with an increased risk of cardiovascular events. We aimed at assessing the mean platelet volume (MPV), as an index of platelet activation, in COPD patients both when stable or during acute exacerbation (AE). Research design and methods A total of 478 patients (75 with AE) and 72 age-matched healthy controls were enrolled. Medical history, comorbidities, medications, pulmonary function tests, MPV and blood cell count, erythrocyte sedimentation rate (ERS) and C-reactive protein (CRP) were recorded. Results MPV was higher in COPD than in controls (8.7 +/- 1.1 fL and 8.4 +/- 0.8 fL respectively, p = 0.025) and increased with the severity of the disease as assessed by post-bronchodilator forced expiratory volume in the first second (FEV1) categorized I to IV (p > 0.05). MPV was higher in COPD patients during AE compared with stable condition (8.7 +/- 1.0 fL and 8.9 +/- 1.0 fL, p = 0.021). MPV >=10.5 fL correlated with the presence of at least one co-existing cardiovascular disease (p = 0.008). No correlation was observed between MPV and CRP or ERS in patients or in controls. A negative correlation was found between platelet count and MPV in COPD patients. Limitations The retrospective design did not allow the assessment of a clear cause-effect relationship between MPV and all the pathophysiological factors considered. Conclusions Elevated MPV is associated with lower platelet count and with cardiovascular comorbidity in COPD patients. MPV is higher in more severe COPD and during AE. Present findings warrant future studies to confirm a possible clinically relevant role for platelet activation in cardiovascular risk in the COPD population. PMID- 26824632 TI - Application of Market Basket Analysis for the Visualization of Transaction Data Based on Human Lifestyle and Spectroscopic Measurements. AB - With the innovation of high-throughput metabolic profiling methods such as nuclear magnetic resonance (NMR), data mining techniques that can reveal valuable information from substantial data sets are constantly desired in this field. In particular, for the analytical assessment of various human lifestyles, advanced computational methods are ultimately needed. In this study, we applied market basket analysis, which is generally applied in social sciences such as marketing, and used transaction data derived from dietary intake information and urinary chemical data generated using NMR and inductively coupled plasma optical emission spectrometry measurements. The analysis revealed several relationships, such as fish diets with high trimethylamine N-oxide excretion and N-methylnicotinamide excreted at higher levels in the morning and produced from a protein that was consumed one day prior. Therefore, market basket analysis can be applied to metabolic profiling to effectively understand the relationships between metabolites and lifestyle. PMID- 26824633 TI - Postural responses applied in a control model in cochlear implant users with pre lingual hearing loss. AB - Conclusions The assessment of postural responses (PR) based in a feedback control system model shows selective gains in different bands of frequencies adaptable with child development. Objective PR characterization of pre-lingual cochlear implant users (CIU) in different sensory conditions. Methods Total energy consumption of the body's center of pressure signal (ECCOP) and its distribution in three bands of frequencies: band 1 (0-0.1 Hz), band 2 (0.1-0.7 Hz), and band 3 (0.7-20 Hz) was measured in a sample of 18 CIU (8-16 years old) and in a control group (CG) (8-15 years old). They were assessed in a standing position on a force platform in two sensory conditions: 1 = Eyes open. 2 = Eyes closed and standing on foam. Results In condition 1, total ECCOP of PR and its proportion of energy consumption in the three bands of frequencies were similar between CIU and CG (p > 0.05). In condition 2, CIU have significantly higher ECCOP, mainly in high frequencies (bands 2 and 3) (p < 0.05). ECCOP values decreased with age also, mainly in bands 2 and 3. This behavior is interpreted in the control system model proposed as an adaptation process related with child development. PMID- 26824635 TI - Degree of correspondence between daily monitoring and retrospective recall of alcohol use among men and women with comorbid AUD and PTSD. AB - BACKGROUND AND OBJECTIVES: The majority of studies that have identified good correspondence between daily monitoring and retrospective recall of alcohol use have included participants who are relatively stable, are moderate drinkers, report abstinence, and are not diagnosed with comorbid disorders. The current study examined degree of correspondence between alcohol use that was reported daily via interactive voice response (IVR) telephone monitoring and retrospectively using an abbreviated Form-90 (Form-35) covering the same 35-day time period. METHODS: Participants were 54 men and women with comorbid alcohol dependence and posttraumatic stress disorder (PTSD) who reported drinking during the time period. RESULTS: Results indicated that participants reported more drinking days via IVR. Correspondence was strong between the reporting methods for aggregate-level alcohol use variables, including presence/absence of drinking days and heavy drinking days and standard drinks, and associations increased for weeks closer to the assessment date for drinking days and heavy drinking days. Day-to-day agreement was moderate for drinking days and heavy drinking days, though there was large between-person variability in correspondence between reporting methods. Post-hoc analyzes suggested that men and participants who drink more tend to have lower correspondence between assessment methods. DISCUSSION AND CONCLUSIONS: Overall, findings partially replicated previous research and extend our knowledge of alcohol assessment in a comorbid sample. SCIENTIFIC SIGNIFICANCE: Findings highlight the importance of considering the influence that moderating variables have on reporting of alcohol use. PMID- 26824634 TI - Metabolic effects of a 13-weeks lifestyle intervention in older adults: The Growing Old Together Study. AB - For people in their 40s and 50s, lifestyle programs have been shown to improve metabolic health. For older adults, however, it is not clear whether these programs are equally healthy. In the Growing Old Together study, we applied a 13 weeks lifestyle program, with a target of 12.5% caloric restriction and 12.5% increase in energy expenditure through an increase in physical activity, in 164 older adults (mean age=63.2 years; BMI=23-35 kg/m2). Mean weight loss was 4.2% (SE=2.8%) of baseline weight, which is comparable to a previous study in younger adults. Fasting insulin levels, however, showed a much smaller decrease (0.30 mU/L (SE=3.21)) and a more heterogeneous response (range=2.0-29.6 mU/L). Many other parameters of metabolic health, such as blood pressure, and thyroid, glucose and lipid metabolism improved significantly. Many 1H-NMR metabolites changed in a direction previously associated with a low risk of type 2 diabetes and cardiovascular disease and partially independently of weight loss. In conclusion, 25% reduction in energy balance for 13 weeks induced a metabolic health benefit in older adults, monitored by traditional and novel metabolic markers. PMID- 26824636 TI - Meta-analysis of diagnostic value of serum Carbohydrate antigen 199 in pancreatic cancer. AB - INTRODUCTION: Carbohydrate antigen 199 (CA199) has been used as a new promising serum biomarker for the diagnosis of pancreatic cancer. But its utility was full of controversies. This study sought to determine the diagnosis value of serum CA199 in pancreatic cancer through enrolling all the related eligible studies. EVIDENCE ACQUISITION: We searched PubMed, Medline, Embase, ISI databases to collect articles in English that evaluated the diagnostic value of CA199 in patients with pancreatic cancer. Two reviewers independently assessed the methodological quality of each study using the quality assessment of diagnostic accuracy studies tool. The data were analyzed using Meta-Disc (Version 1.4) and Stata (Version 12.0) software. We estimated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC). A total of 11 studies involving 2,316 individuals were included. EVIDENCE SYNTHESIS: The pooled sensitivity and specificity for CA199 in diagnosing pancreatic cancer were 0.80 (95% confidence interval [CI], 0.77-0.82) and 0.80 (95% CI: 0.77-0.82), respectively. The DOR was 14.79 (95% CI: 8.55-25.59) and the area under the SROC curve was 0.87. CONCLUSIONS: The current analyses indicated that CA199 is a valuable marker in the diagnosis of pancreatic cancer. PMID- 26824637 TI - Headache, Atypical Facial Pain, and a Syrinx. PMID- 26824639 TI - Gaze-contingent training enhances perceptual skill acquisition. AB - The purpose of this study was to determine whether decision-making skill in perceptual-cognitive tasks could be enhanced using a training technique that impaired selective areas of the visual field. Recreational basketball players performed perceptual training over 3 days while viewing with a gaze-contingent manipulation that displayed either (a) a moving window (clear central and blurred peripheral vision), (b) a moving mask (blurred central and clear peripheral vision), or (c) full (unrestricted) vision. During the training, participants watched video clips of basketball play and at the conclusion of each clip made a decision about to which teammate the player in possession of the ball should pass. A further control group watched unrelated videos with full vision. The effects of training were assessed using separate tests of decision-making skill conducted in a pretest, posttest, and 2-week retention test. The accuracy of decision making was greater in the posttest than in the pretest for all three intervention groups when compared with the control group. Remarkably, training with blurred peripheral vision resulted in a further improvement in performance from posttest to retention test that was not apparent for the other groups. The type of training had no measurable impact on the visual search strategies of the participants, and so the training improvements appear to be grounded in changes in information pickup. The findings show that learning with impaired peripheral vision offers a promising form of training to support improvements in perceptual skill. PMID- 26824638 TI - Neural bandwidth of veridical perception across the visual field. AB - Neural undersampling of the retinal image limits the range of spatial frequencies that can be represented veridically by the array of retinal ganglion cells conveying visual information from eye to brain. Our goal was to demarcate the neural bandwidth and local anisotropy of veridical perception, unencumbered by optical imperfections of the eye, and to test competing hypotheses that might account for the results. Using monochromatic interference fringes to stimulate the retina with high-contrast sinusoidal gratings, we measured sampling-limited visual resolution along eight meridians from 0 degrees to 50 degrees of eccentricity. The resulting isoacuity contour maps revealed all of the expected features of the human array of retinal ganglion cells. Contours in the radial fringe maps are elongated horizontally, revealing the functional equivalent of the anatomical visual streak, and are extended into nasal retina and superior retina, indicating higher resolution along those meridians. Contours are larger in diameter for radial gratings compared to tangential or oblique gratings, indicating local anisotropy with highest bandwidth for radially oriented gratings. Comparison of these results to anatomical predictions indicates acuity is proportional to the sampling density of retinal ganglion cells everywhere in the retina. These results support the long-standing hypothesis that "pixel density" of the discrete neural image carried by the human optic nerve limits the spatial bandwidth of veridical perception at all retinal locations. PMID- 26824640 TI - Eye guidance during real-world scene search: The role color plays in central and peripheral vision. AB - The visual system utilizes environmental features to direct gaze efficiently when locating objects. While previous research has isolated various features' contributions to gaze guidance, these studies generally used sparse displays and did not investigate how features facilitated search as a function of their location on the visual field. The current study investigated how features across the visual field--particularly color--facilitate gaze guidance during real-world search. A gaze-contingent window followed participants' eye movements, restricting color information to specified regions. Scene images were presented in full color, with color in the periphery and gray in central vision or gray in the periphery and color in central vision, or in grayscale. Color conditions were crossed with a search cue manipulation, with the target cued either with a word label or an exact picture. Search times increased as color information in the scene decreased. A gaze-data based decomposition of search time revealed color mediated effects on specific subprocesses of search. Color in peripheral vision facilitated target localization, whereas color in central vision facilitated target verification. Picture cues facilitated search, with the effects of cue specificity and scene color combining additively. When available, the visual system utilizes the environment's color information to facilitate different real world visual search behaviors based on the location within the visual field. PMID- 26824642 TI - An Amylase-Responsive Bolaform Supra-Amphiphile. AB - An amylase-responsive bolaform supra-amphiphile was constructed by the complexation between beta-cyclodextrin and a bolaform covalent amphiphile on the basis of host-guest interaction. The bolaform covalent amphiphile could self assemble in solution, forming sheet-like aggregates and displaying weak fluorescence because of aggregation-induced quenching. The addition of beta cyclodextrin led to the formation of the bolaform supra-amphiphile, prohibiting the aggregation of the bolaform covalent amphiphile and accompanying with the significant recovery of fluorescence. Upon the addition of alpha-amylase, with the degradation beta-cyclodextrin, the fluorescence of the supra-amphiphile would quench gradually and significantly, and the quenching rate linearly correlated to the concentration of alpha-amylase. This study enriches the field of supra amphiphiles on the basis of noncovalent interactions, and moreover, it may provide a facile way to estimate the activity of alpha-amylase. PMID- 26824641 TI - Glycine supplementation in vitro enhances porcine preimplantation embryo cell number and decreases apoptosis but does not lead to live births. AB - Most in vitro culture conditions are less-than-optimal for embryo development. Here, we used a transcriptional-profiling database to identify culture-induced differences in gene expression in porcine blastocysts compared to in vivo produced counterparts. Genes involved in glycine transport (SLC6A9), glycine metabolism (GLDC, GCSH, DLD, and AMT), and serine metabolism (PSAT1, PSPH, and PHGDH) were differentially expressed. Addition of 10 mM glycine to the culture medium (currently containing 0.1 mM) reduced the abundance of SLC6A9 transcript and increased total cell number, primarily in the trophectoderm lineage (P = 0.003); this was likely by decreasing the percentage of apoptotic nuclei. As serine and glycine can be reversibly metabolized by serine hydroxymethyltransferase 2 (SHMT2), we assessed the abundance of SHMT2 transcript as well as its functional role by inhibiting it with aminomethylphosphonic acid (AMPA), a glycine analog, during in vitro culture. Both AMPA supplementation and elevated glycine decreased the mRNA abundance of SHMT2 and tumor protein p53 (TP53), which is activated in response to cellular stress, compared to controls (P <= 0.02). On the other hand, mitochondrial activity of blastocysts, mtDNA copy number, and abundance of mitochondria-related transcripts did not differ between control and 10 mM glycine culture conditions. Despite improvements to these metrics of blastocyst quality, transfer of embryos cultured in 10 mM glycine did not result in pregnancy whereas the transfer of in vitro-produced embryos cultured in control medium yielded live births. Mol. Reprod. Dev. 83: 246-258, 2016. (c) 2016 The Authors. PMID- 26824643 TI - Mimicking of Arginine by Functionalized N(omega)-Carbamoylated Arginine As a New Broadly Applicable Approach to Labeled Bioactive Peptides: High Affinity Angiotensin, Neuropeptide Y, Neuropeptide FF, and Neurotensin Receptor Ligands As Examples. AB - Derivatization of biologically active peptides by conjugation with fluorophores or radionuclide-bearing moieties is an effective and commonly used approach to prepare molecular tools and diagnostic agents. Whereas lysine, cysteine, and N terminal amino acids have been mostly used for peptide conjugation, we describe a new, widely applicable approach to peptide conjugation based on the nonclassical bioisosteric replacement of the guanidine group in arginine by a functionalized carbamoylguanidine moiety. Four arginine-containing peptide receptor ligands (angiotensin II, neurotensin(8-13), an analogue of the C-terminal pentapeptide of neuropeptide Y, and a neuropeptide FF analogue) were subject of this proof-of concept study. The N(omega)-carbamoylated arginines, bearing spacers with a terminal amino group, were incorporated into the peptides by standard Fmoc solid phase peptide synthesis. The synthesized chemically stable peptide derivatives showed high receptor affinities with Ki values in the low nanomolar range, even when bulky fluorophores had been attached. Two new tritiated tracers for angiotensin and neurotensin receptors are described. PMID- 26824645 TI - A Cell-ebration of Induced Pluripotency. PMID- 26824644 TI - Long-Term Persistence of Bi-functionality Contributes to the Robustness of Microbial Life through Exaptation. AB - Modern enzymes are highly optimized biocatalysts that process their substrates with extreme efficiency. Many enzymes catalyze more than one reaction; however, the persistence of such ambiguities, their consequences and evolutionary causes are largely unknown. As a paradigmatic case, we study the history of bi functionality for a time span of approximately two billion years for the sugar isomerase HisA from histidine biosynthesis. To look back in time, we computationally reconstructed and experimentally characterized three HisA predecessors. We show that these ancient enzymes catalyze not only the HisA reaction but also the isomerization of a similar substrate, which is commonly processed by the isomerase TrpF in tryptophan biosynthesis. Moreover, we found that three modern-day HisA enzymes from Proteobacteria and Thermotogae also possess low TrpF activity. We conclude that this bi-functionality was conserved for at least two billion years, most likely without any evolutionary pressure. Although not actively selected for, this trait can become advantageous in the case of a gene loss. Such exaptation is exemplified by the Actinobacteria that have lost the trpF gene but possess the bi-functional HisA homolog PriA, which adopts the roles of both HisA and TrpF. Our findings demonstrate that bi functionality can perpetuate in the absence of selection for very long time spans. PMID- 26824647 TI - Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans. AB - It is often presented as common knowledge that, in the human body, bacteria outnumber human cells by a ratio of at least 10:1. Revisiting the question, we find that the ratio is much closer to 1:1. PMID- 26824648 TI - Epigenetic ON/OFF Switches for Obesity. AB - Heritable epigenetic mechanisms might contribute to the worldwide increase in the prevalence of obesity. Dalgaard et al. identify an epigenetic molecular switch that controls body weight control. The discovery suggests the existence of mammalian polyphenism in energy metabolism and might have implications for strategies to limit the obesity epidemic. PMID- 26824649 TI - Reflexes in Immunity. AB - Simple reflex circuits provide crucial infrastructure for the neurological control of organ systems--even the immune system. Now, Gabanyi et al. reveal a reflex mechanism in gut activated by the presence of pathogens that forces macrophages into a tissue protective phenotype. PMID- 26824650 TI - Flexible Ion Barrier. AB - The central vasculature of plant roots is protected by a hydrophobic ring of endodermal cells that are enclosed by lamellae of suberin. Barberon et al. demonstrate that endodermal suberization plasticity facilitates ion homeostasis, with antithetical regulation of suberin deposition and degradation by the phytohormones abscisic acid and ethylene. PMID- 26824651 TI - The Importance of Timing. AB - Building a nervous system requires a precise sequence of genetic transitions, mediated in part by the temporal and spatial regulation of transcription factors. Quan et al. add to our understanding of this regulation by describing an evolutionarily conserved post-translational mechanism that rapidly extinguishes proneural protein activity in neural precursors. PMID- 26824652 TI - Alpha and Beta Type 1 Interferon Signaling: Passage for Diverse Biologic Outcomes. AB - Type I interferon (IFN-I) elicits a complex cascade of events in response to microbial infection. Here, we review recent developments illuminating the large number of IFN-I species and describing their unique biologic functions. PMID- 26824653 TI - Trim28 Haploinsufficiency Triggers Bi-stable Epigenetic Obesity. AB - More than one-half billion people are obese, and despite progress in genetic research, much of the heritability of obesity remains enigmatic. Here, we identify a Trim28-dependent network capable of triggering obesity in a non Mendelian, "on/off" manner. Trim28(+/D9) mutant mice exhibit a bi-modal body weight distribution, with isogenic animals randomly emerging as either normal or obese and few intermediates. We find that the obese-"on" state is characterized by reduced expression of an imprinted gene network including Nnat, Peg3, Cdkn1c, and Plagl1 and that independent targeting of these alleles recapitulates the stochastic bi-stable disease phenotype. Adipose tissue transcriptome analyses in children indicate that humans too cluster into distinct sub-populations, stratifying according to Trim28 expression, transcriptome organization, and obesity-associated imprinted gene dysregulation. These data provide evidence of discrete polyphenism in mouse and man and thus carry important implications for complex trait genetics, evolution, and medicine. PMID- 26824654 TI - Toll Receptor-Mediated Hippo Signaling Controls Innate Immunity in Drosophila. AB - The Hippo signaling pathway functions through Yorkie to control tissue growth and homeostasis. How this pathway regulates non-developmental processes remains largely unexplored. Here, we report an essential role for Hippo signaling in innate immunity whereby Yorkie directly regulates the transcription of the Drosophila IkappaB homolog, Cactus, in Toll receptor-mediated antimicrobial response. Loss of Hippo pathway tumor suppressors or activation of Yorkie in fat bodies, the Drosophila immune organ, leads to elevated cactus mRNA levels, decreased expression of antimicrobial peptides, and vulnerability to infection by Gram-positive bacteria. Furthermore, Gram-positive bacteria acutely activate Hippo-Yorkie signaling in fat bodies via the Toll-Myd88-Pelle cascade through Pelle-mediated phosphorylation and degradation of the Cka subunit of the Hippo inhibitory STRIPAK PP2A complex. Our studies elucidate a Toll-mediated Hippo signaling pathway in antimicrobial response, highlight the importance of regulating IkappaB/Cactus transcription in innate immunity, and identify Gram positive bacteria as extracellular stimuli of Hippo signaling under physiological settings. PMID- 26824655 TI - Electron Transport Chain Remodeling by GSK3 during Oogenesis Connects Nutrient State to Reproduction. AB - Reproduction is heavily influenced by nutrition and metabolic state. Many common reproductive disorders in humans are associated with diabetes and metabolic syndrome. We characterized the metabolic mechanisms that support oogenesis and found that mitochondria in mature Drosophila oocytes enter a low-activity state of respiratory quiescence by remodeling the electron transport chain (ETC). This shift in mitochondrial function leads to extensive glycogen accumulation late in oogenesis and is required for the developmental competence of the oocyte. Decreased insulin signaling initiates ETC remodeling and mitochondrial respiratory quiescence through glycogen synthase kinase 3 (GSK3). Intriguingly, we observed similar ETC remodeling and glycogen uptake in maturing Xenopus oocytes, suggesting that these processes are evolutionarily conserved aspects of oocyte development. Our studies reveal an important link between metabolism and oocyte maturation. PMID- 26824657 TI - Post-translational Control of the Temporal Dynamics of Transcription Factor Activity Regulates Neurogenesis. AB - Neurogenesis is initiated by the transient expression of the highly conserved proneural proteins, bHLH transcriptional regulators. Here, we discover a conserved post-translational switch governing the duration of proneural protein activity that is required for proper neuronal development. Phosphorylation of a single Serine at the same position in Scute and Atonal proneural proteins governs the transition from active to inactive forms by regulating DNA binding. The equivalent Neurogenin2 Threonine also regulates DNA binding and proneural activity in the developing mammalian neocortex. Using genome editing in Drosophila, we show that Atonal outlives its mRNA but is inactivated by phosphorylation. Inhibiting the phosphorylation of the conserved proneural Serine causes quantitative changes in expression dynamics and target gene expression resulting in neuronal number and fate defects. Strikingly, even a subtle change from Serine to Threonine appears to shift the duration of Atonal activity in vivo, resulting in neuronal fate defects. PMID- 26824656 TI - Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin Cytoskeleton. AB - The phosphoinositide 3-kinase (PI3K) pathway regulates multiple steps in glucose metabolism and also cytoskeletal functions, such as cell movement and attachment. Here, we show that PI3K directly coordinates glycolysis with cytoskeletal dynamics in an AKT-independent manner. Growth factors or insulin stimulate the PI3K-dependent activation of Rac, leading to disruption of the actin cytoskeleton, release of filamentous actin-bound aldolase A, and an increase in aldolase activity. Consistently, PI3K inhibitors, but not AKT, SGK, or mTOR inhibitors, cause a significant decrease in glycolysis at the step catalyzed by aldolase, while activating PIK3CA mutations have the opposite effect. These results point toward a master regulatory function of PI3K that integrates an epithelial cell's metabolism and its form, shape, and function, coordinating glycolysis with the energy-intensive dynamics of actin remodeling. PMID- 26824658 TI - LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength. AB - The volume-regulated anion channel (VRAC) is activated when a cell swells, and it plays a central role in maintaining cell volume in response to osmotic challenges. SWELL1 (LRRC8A) was recently identified as an essential component of VRAC. However, the identity of the pore-forming subunits of VRAC and how the channel is gated by cell swelling are unknown. Here, we show that SWELL1 and up to four other LRRC8 subunits assemble into heterogeneous complexes of ~800 kDa. When reconstituted into bilayers, LRRC8 complexes are sufficient to form anion channels activated by osmolality gradients. In bilayers, as well as in cells, the single-channel conductance of the complexes depends on the LRRC8 composition. Finally, low ionic strength (Gamma) in the absence of an osmotic gradient activates the complexes in bilayers. These data demonstrate that LRRC8 proteins together constitute the VRAC pore and that hypotonic stress can activate VRAC through a decrease in cytoplasmic Gamma. PMID- 26824659 TI - Muscle-type Identity of Proprioceptors Specified by Spatially Restricted Signals from Limb Mesenchyme. AB - The selectivity with which proprioceptive sensory neurons innervate their central and peripheral targets implies that they exhibit distinctions in muscle-type identity. The molecular correlates of proprioceptor identity and its origins remain largely unknown, however. In screens to define muscle-type proprioceptor character, we find all-or-none differences in gene expression for proprioceptors that control antagonistic muscles at a single hindlimb joint. Analysis of three of these genes, cadherin13 (cdh13), semaphorin5a (sema5a), and cartilage-acidic protein-1 (crtac1), reveals expression in proprioceptor subsets that supply muscle groups located at restricted dorsoventral and proximodistal domains of the limb. Genetically altering the dorsoventral character of the limb mesenchyme elicits a change in the profile of proprioceptor cdh13, sema5a, and crtac1 expression. These findings indicate that proprioceptors acquire aspects of their muscle-type identity in response to mesenchymal signals expressed in restricted proximodistal and dorsoventral domains of the developing limb. PMID- 26824660 TI - Cell-Type-Specific Control of Brainstem Locomotor Circuits by Basal Ganglia. AB - The basal ganglia (BG) are critical for adaptive motor control, but the circuit principles underlying their pathway-specific modulation of target regions are not well understood. Here, we dissect the mechanisms underlying BG direct and indirect pathway-mediated control of the mesencephalic locomotor region (MLR), a brainstem target of BG that is critical for locomotion. We optogenetically dissect the locomotor function of the three neurochemically distinct cell types within the MLR: glutamatergic, GABAergic, and cholinergic neurons. We find that the glutamatergic subpopulation encodes locomotor state and speed, is necessary and sufficient for locomotion, and is selectively innervated by BG. We further show activation and suppression, respectively, of MLR glutamatergic neurons by direct and indirect pathways, which is required for bidirectional control of locomotion by BG circuits. These findings provide a fundamental understanding of how BG can initiate or suppress a motor program through cell-type-specific regulation of neurons linked to specific actions. PMID- 26824663 TI - Timeline: iPSCs--The First Decade. AB - Research into induced pluripotent stem cells (iPSCs) has expanded at a remarkable pace in the decade since Shinya Yamanaka and Kazutoshi Takahashi first reported their groundbreaking discovery in 2006. This Timeline highlights the key events in the development of this field, including basic insights into the production of iPSCs and how they have been applied to improve our understanding and treatment of human disease. PMID- 26824662 TI - Parsing the Interferon Transcriptional Network and Its Disease Associations. AB - Type 1 interferon (IFN) is a key mediator of organismal responses to pathogens, eliciting prototypical "interferon signature genes" that encode antiviral and inflammatory mediators. For a global view of IFN signatures and regulatory pathways, we performed gene expression and chromatin analyses of the IFN-induced response across a range of immunocyte lineages. These distinguished ISGs by cell type specificity, kinetics, and sensitivity to tonic IFN and revealed underlying changes in chromatin configuration. We combined 1,398 human and mouse datasets to computationally infer ISG modules and their regulators, validated by genetic analysis in both species. Some ISGs are controlled by Stat1/2 and Irf9 and the ISRE DNA motif, but others appeared dependent on non-canonical factors. This regulatory framework helped to interpret JAK1 blockade pharmacology, different clusters being affected under tonic or IFN-stimulated conditions, and the IFN signatures previously associated with human diseases, revealing unrecognized subtleties in disease footprints, as affected by human ancestry. PMID- 26824664 TI - Hypertension and Diabetic Nephropathy. AB - Diabetic nephropathy (DN) is a major complication of both type 1 and type 2 diabetes. DN is the most common cause of end-stage renal disease, and it markedly enhances the risk of cardiovascular events. An elevated urinary albumin excretion rate, increased blood pressure (BP), and a continual loss of renal function are characteristics of DN. Screening for microalbuminuria is central to diabetes care, and antihypertensive agents are used for the primary prevention and treatment of DN. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers play central roles and have protective properties beyond their BP-lowering effects. BP control in relation to DN is the main focus of this review, but tight control of the glucose level is equally important. There is an unmet need for new treatment options, and while a few promising candidates exist, their roles in clinical practice have not yet been determined. PMID- 26824666 TI - Development and Application of a High-Throughput Fluorescence Polarization Assay to Target Pim Kinases. AB - Pim proteins consisting of three isoforms (Pim-1, Pim-2, and Pim-3) are a family of serine/threonine kinases that regulate fundamental cellular responses such as cell growth, differentiation, and apoptosis. Overexpression of the Pim kinases has been linked to a wide variety of hematological and solid tumors. Thus, all three Pim kinases have been studied as promising targets for anticancer therapy. Here, we report on the development and optimization of an immobilized metal ion affinity partitioning (IMAP) fluorescence polarization (FP) method for Pim kinases. In this homogeneous 384-well assay method, fluorescein-labeled phosphopeptides are captured on cationic nanoparticles through interactions with immobilized trivalent metals, resulting in high polarization values. The apparent Km values for adenosine triphosphate (ATP) were determined to be 45 +/- 7, 6.4 +/ 2, and 29 +/- 5 MUM for Pim-1, Pim-2, and Pim-3, respectively. The assay yielded robustness with Z'-factors of >0.75 and low day-to-day variability (CV <5%) for all three Pim kinases. The IMAP FP assay was further validated by determining IC50 values for staurosporine and a known Pim inhibitor. We have also used an IMAP FP assay to examine whether compound 1, an ATP mimetic inhibitor designed through structure-based drug design, is indeed an ATP-competitive inhibitor of Pim kinases. Kinetic analysis based on Lineweaver-Burk plots showed that the inhibition mechanism of compound 1 is ATP competitive against all three Pim isoforms. The optimized IMAP assay for Pim kinases not only allows for high throughput screening but also facilitates the characterization of novel Pim inhibitors for drug development. PMID- 26824665 TI - The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy. AB - BACKGROUND: Pulmonary arterial hypertension is characterized by increased pressure overload that leads to right ventricular hypertrophy (RVH). GPR91 is a formerly orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate; however, its role in RVH remains unknown. METHODS AND RESULTS: We investigated the role of succinate-GPR91 signaling in a pulmonary arterial banding (PAB) model of RVH induced by pressure overload in SD rats. GPR91 was shown to be located in cardiomyocytes. In the sham and PAB rats, succinate treatment further aggravated RVH, up-regulated RVH-associated genes and increased p-Akt/t-Akt levels in vivo. In vitro, succinate treatment up-regulated the levels of the hypertrophic gene marker anp and p-Akt/t-Akt in cardiomyocytes. All these effects were inhibited by the PI3K antagonist wortmannin both in vivo and in vitro. Finally, we noted that the GPR91-PI3K/Akt axis was also up regulated compared to that in human RVH. CONCLUSIONS: Our findings indicate that succinate-GPR91 signaling may be involved in RVH via PI3K/Akt signaling in vivo and in vitro. Therefore, GPR91 may be a novel therapeutic target for treating pressure overload-induced RVH. PMID- 26824667 TI - Psychological Differences toward Pedestrian Red Light Crossing between University Students and Their Peers. AB - Based on our site investigation conducted in 2013, we found that the pedestrian red light crossing at the midblock connecting the campus of Southwest University and living area was low, where most of pedestrians are university students and staff. This paper reports a supplementary work applying the Theory of Planned Behaviour (TPB) to identify any psychological differences toward pedestrian red light crossing between university students and their peers. Three social groups participated in the investigation. The first group is the university students in Grade one (Group 1), the other two groups are their previous senior middle school classmates who are now working full time (Group 2) or who are now out of work and school (Group 3). The statistical results indicated The TPB components accounted for 42.9%, 55.3% and 55.4% of the variance of red signal crossing intention for Group 1, Group 2 and Group 3 in the depicted road crossing scenario. The data also showed that there are obvious differences among the participants' responses to "refrain from crossing" between university students and others, and the subsequent regression analysis revealed the ability to "refrain from crossing" played the most important role in the intention of red light crossing in the depicted scenario. PMID- 26824668 TI - Opinion: Comment on Evaluation and Treatment of Cryptorchidism: AUA/AAP and Nordic Consensus Guidelines. AB - The ultimate goal in the treatment of cryptorchidism is to achieve normal fertility. However, in a substantial number of cryptorchid males, early and apparently successful orchidopexy does not improve fertility as it does not address the underlying pathophysiological cause, namely, the impaired transformation of gonocytes into Ad spermatogonia. It is important to realize that over half the patients presenting with unilateral cryptorchidism and the majority of those presenting with bilateral cryptorchidism have abnormal spermiogram which indicates that unilateral cryptorchidism is in fact a bilateral disease and therefore a serious andrological problem. More importantly, only testicular biopsy can nowadays determine which patient should benefit from hormonal therapy. This means that the rationale behind testicular biopsy is both diagnostic and therapeutic, particularly since LH-RHa hormonal therapy is a worthwhile solution to this andrological problem. In boys with a high risk of azoospermia development, adequate treatment with low doses of LH-RHa allowed 86% of subjects to achieve a normal sperm count. This strongly contrasts with the results of the 'surgery-only' group where not a single patient had a normal spermiogram and 20% suffered from azoospermia. Testicular biopsy is all the more justified that it allowed the detection of in situ carcinoma in 0.6% of all the cryptorchid boys studied. Even if hormonal pre-treatment only achieves successful epididymo-testicular descent in 20% of cases, this treatment should remain the first therapeutic choice because it may avoid resorting to surgery. In addition, it has no adverse effect on fertility and, in unsuccessful cases, facilitates orchidopexy and considerably helps reduce the incidence of post-surgical testicular atrophy, whether unilateral or, and this is a much more serious event, bilateral. PMID- 26824669 TI - Stereoselective Synthesis of Isochromanones by an Asymmetric Ortho-Lithiation Strategy: Synthetic Access to the Isochromanone Core of the Ajudazols. AB - Full details on the design, development, and application of a highly stereoselective strategy for the synthesis of isochromanones are reported. The method is based on an asymmetric ortho lithiation with aldehyde electrophiles and utilizes the chiral memory of a preoriented atropisomeric amide axis for stereocontrol. For direct transformation of sterically hindered amides to isochromanones, efficient and mild one-pot protocols involving either O alkylation or acidic microwave activation were developed. The procedures may be applied also to highly functionalized as well as stereochemically complex and sensitive substrates and demonstrate a high protective group tolerance. Furthermore, asymmetric crotylborations of axially chiral amides were studied in detail. These methodologies enable a general access to all possible stereoisomers of hydroxyl-isochromanones with up to three contiguous stereocenters. The true applicability of our approach was finally demonstrated by synthesis of the authentic anti,anti-configured isochromanone core of the ajudazols, highly potent inhibitors of the mitochondrial respiratory chain from myxobacteria. PMID- 26824670 TI - Shoulder function, pain and health related quality of life in adults with joint hypermobility syndrome/Ehlers-Danlos syndrome-hypermobility type. AB - Purpose To investigate shoulder function, pain and Health-Related Quality of life (HRQoL) among adults with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT), compared with the general population (controls). Method In a cross-sectional study using postal survey, 110 patients diagnosed with JHS/EDS-HT and 140 gender- and age-matched healthy controls from Statistics Norway participated. Shoulder function, pain and HRQol were registered by Western Ontario Shoulder Instability Index (WOSI), Numerical Rating Scale (NRS), pain drawings, 36-item Short Form (SF-36). Results Eighty-one individuals responded, with response rate 34% (JHS/EDS-HT: 53%, controls: 21%). JHS/EDS-HT had lower shoulder function (WOSI total: 49.9 versus 83.3; p < 0.001), lower HRQol on SF-36 Physical Component Scale (PCS: 28.1 versus 49.9; p < 0.001), and higher pain intensity (NRS: 6.4 versus 2.7; p < 0.001) than controls. Neck and shoulder joints were rated as primary painful areas in both groups, with significantly higher frequency in JHS/EDS-HT (neck: 90% versus 27%; shoulder: 80% versus 37%). Further, JHS/EDS-HT most often reported generalized pain (96%). Conclusions Adults with JHS/EDS-HT have impaired shoulder function, increased pain intensity, as well as reduced physical HRQoL compared with controls. Although neck and shoulder were most frequently rated as painful, significantly more JHS/EDS-HT also reported generalized pain compared to controls. Implications for Rehabilitation Adults with JHS/EDS-HT have impaired shoulder function, and most often painful areas in the neck and shoulder joints, which need to be targeted in the treatment strategy. Compared with the general population adults with JHS/EDS HT have reduced physical HRQoL, supporting a physical approach for this group. Adults with JHS/EDS-HT may present with both specific painful joints and generalized pain. PMID- 26824661 TI - Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma. AB - Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes. PMID- 26824671 TI - Estimating Population Density of the San Martin Titi Monkey (Callicebus oenanthe) in Peru Using Vocalisations. AB - We calculated the population density of the critically endangered Callicebus oenanthe in the Ojos de Agua Conservation Concession, a dry forest area in the department of San Martin, Peru. Results showed significant differences (p < 0.01) in group densities between forest boundaries (16.5 groups/km2, IQR = 21.1-11.0) and forest interior (4.0 groups/km2, IQR = 5.0-0.0), suggesting the 2,550-ha area harbours roughly 1,150 titi monkeys. This makes Ojos de Agua an important cornerstone in the conservation of the species, because it is one of the largest protected areas where the species occurs. PMID- 26824673 TI - Antidiabetic actions of cocoa flavanols. AB - Prevention of diabetes mellitus type 2 (DMT2) through the diet is receiving a growing interest and cocoa because of its polyphenolic compounds, mainly flavanols, has become an important potential chemopreventive natural agent. Cocoa and its main flavanols might contribute to prevent or delay diabetes mellitus type 2 by modulating insulin secretion in beta-pancreatic cells and targeting insulin-sensitive tissues because of their insulin-like activity or through the regulation of key proteins of the insulin signaling route. Among other actions, cocoa flavanols have been proved to enhance glucose uptake through the promotion of glucose transport, to repress glucose production, or to improve lipid metabolism. Nevertheless, the molecular mechanisms of action involved in these effects are not fully understood and many points remain to be clarified. This review provides insights into the molecular machinery of the chemopreventive activity of cocoa and its flavanols by compiling cell culture and animal models studies, as well as evidence from human interventional trials. PMID- 26824672 TI - Cerebral Blood Volume ASPECTS Is the Best Predictor of Clinical Outcome in Acute Ischemic Stroke: A Retrospective, Combined Semi-Quantitative and Quantitative Assessment. AB - INTRODUCTION: The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned. METHODS: 62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded. RESULTS: Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS <= 2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome. CONCLUSIONS: Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size. PMID- 26824674 TI - Interactions of Environmental Factors and APOA1-APOC3-APOA4-APOA5 Gene Cluster Gene Polymorphisms with Metabolic Syndrome. AB - OBJECTIVE: The present study investigated the prevalence and risk factors for Metabolic syndrome. We evaluated the association between single nucleotide polymorphisms (SNPs) in the apolipoprotein APOA1/C3/A4/A5 gene cluster and the MetS risk and analyzed the interactions of environmental factors and APOA1/C3/A4/A5 gene cluster polymorphisms with MetS. METHODS: A study on the prevalence and risk factors for MetS was conducted using data from a large cross sectional survey representative of the population of Jilin Province situated in northeastern China. A total of 16,831 participations were randomly chosen by multistage stratified cluster sampling of residents aged from 18 to 79 years in all nine administrative areas of the province. Environmental factors associated with MetS were examined using univariate and multivariate logistic regression analyses based on the weighted sample data. A sub-sample of 1813 survey subjects who met the criteria for MetS patients and 2037 controls from this case-control study were used to evaluate the association between SNPs and MetS risk. Genomic DNA was extracted from peripheral blood lymphocytes, and SNP genotyping was determined by MALDI-TOF-MS. The associations between SNPs and MetS were examined using a case-control study design. The interactions of environmental factors and APOA1/C3/A4/A5 gene cluster polymorphisms with MetS were assessed using multivariate logistic regression analysis. RESULTS: The overall adjusted prevalence of MetS was 32.86% in Jilin province. The prevalence of MetS in men was 36.64%, which was significantly higher than the prevalence in women (29.66%). MetS was more common in urban areas (33.86%) than in rural areas (31.80%). The prevalence of MetS significantly increased with age (OR = 8.621, 95%CI = 6.594 11.272). Mental labor (OR = 1.098, 95%CI = 1.008-1.195), current smoking (OR = 1.259, 95%CI = 1.108-1.429), excess salt intake (OR = 1.252, 95%CI = 1.149 1.363), and a fruit and dairy intake less than 2 servings a week were positively associated with MetS (P<0.05). A family history of diabetes (OR = 1.630, 95%CI = 1.484-1.791), cardiovascular disease or cerebral diseases (OR = 1.297, 95%CI = 1.211-1.389) was associated with MetS. APOA1 rs670, APOA5 rs662799 and rs651821 revealed significant differences in genotype distributions between the MetS patients and control subjects. The minor alleles of APOA1 rs670, APOA5 rs662799 and rs651821, and APOA5 rs2075291 were associated with MetS (P<0.0016). APOA1 rs5072 and APOC3 rs5128, APOA5 rs651821 and rs662799 were in strong linkage disequilibrium to each other with r2 greater than 0.8. Five haplotypes were associated with an increased risk of MetS (OR = 1.23, 1.58, 1.80, 1.90, and 1.98). When we investigated the interactions of environmental factors and APOA1/C3/A4/A5 gene cluster gene polymorphisms, we found that APOA5 rs662799 had interactions with tobacco use and alcohol consumption (PGE<0.05). CONCLUSIONS: There was a high prevalence of MetS in the northeast of China. Male gender, increasing age, mental labor, family history of diabetes, cardiovascular disease or cerebral diseases, current smoking, excess salt intake, fruit and dairy intake less than 2 servings a week, and drinking were associated with MetS. The APOA1/C3/A4/A5 gene cluster was associated with MetS in the Han Chinese. APOA5 rs662799 had interactions with the environmental factors associated with MetS. PMID- 26824675 TI - An on-chip pollutant toxicity determination based on marine microalgal swimming inhibition. AB - We report the use of microalgal swimming behavior as a sensor signal integrated into microfluidics for a rapid and high-throughput determination of pollutant toxicity. There are two types of chip. A poly(dimethylsiloxane) (PDMS) 12-well chip, used for optimization of experimental conditions (i.e. light level, temperature, initial cellular density and exposure time), can perform twelve parallel tests simultaneously. In a concentration gradient generator (CGG) chip, a CGG connected with diffusible chambers enables a large number of dose-response bioassays to be performed in a simple way. Microalgal swimming was set as a microfluidic bioassay signal and was evaluated as swimming manner, motile percentage (%MOT), curvilinear velocity (VCL), average path velocity (VAP) and straight line velocity (VSL). Under optimized physical conditions, the toxicities of Cu, Pb, phenol and nonylphenol (NP) towards four mobile marine microalgae, Platymonas subcordiformis, Platymonas helgolandica var. tsingtaoensis, Isochrysis galbana and Isochrysis zhanjiangensis sp. nov, were investigated. In all cases, a toxic response (i.e. a dose-related inhibition of swimming) was detected, and a time of only 2 h was needed to predict EC50 values. The 2h-EC50s showed that I. galbana was the most tolerant and that P. subcordiformis was one of the most sensitive. Based on the relative motile percentage data, the EC50 values for Cu of I. galbana and P. subcordiformis were 6.04 and 1.67 MUM, respectively, while for Pb the EC50 values were 15.30 and 3.87 MUM, for phenol the EC50 values were 8.69 and 6.08 mM, and for NP the EC50 values were 29.65 and 14.47 MUM, respectively. Taking into account all the swimming inhibition parameters, MOT provided more sensitive EC results. The sensitivity differences between the velocity parameters (VCL, VAP and VSL) were ascribed to differences in swimming manner of the different classes of microalgae. PMID- 26824676 TI - Communication growth in minimally verbal children with ASD: The importance of interaction. AB - Little is known about language development in children with Autism Spectrum Disorders (ASD) who remain minimally verbal past age 5. While there is evidence that children can develop language after age 5, we lack detailed information. Studies of this population generally focus on discrete language skills without addressing broader social-communication abilities. As communication and social deficits are both inherent to ASD, an examination of not only what language skills are acquired, but how those skills are used in interactions is relevant. Research in typical development has examined how communication interchanges (unbroken back-and-forth exchanges around a unified purpose) develop, which can be used as a framework for studying minimally verbal children. This study examined the interchange use by 55 children with ASD over the course of a 6-month play and engagement-based communication intervention. Half of the children received intervention sessions that also incorporated a speech-generating device (SGD). Interchanges were coded by: frequency, length, function, and initiator (child or adult). Results indicated that children initiated a large proportion of interchanges and this proportion increased over time. The average length and number of interchanges increased over time, with children in the SGD group showing even greater growth. Finally, children's total number of interchanges at baseline was positively associated with their spoken language gains over the course of intervention. This study supports the crucial relationship between social engagement and expressive language development, and highlights the need to include sustained communication interchanges as a target for intervention with this population. Autism Res 2016, 9: 1093-1102. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 26824677 TI - Preliminary Report of Inflammatory Markers, Oxidative Stress, and Insulin Resistance in Adolescents of Different Ethnicities. AB - BACKGROUND: Higher fasting glucose and hemoglobin A1C levels are seen more often in African American (AA) and Hispanic (H) youth, even after adjusting for body mass index (BMI), pointing to other factors that might be promoting abnormal glucose tolerance, such as inflammatory mediators. Our study compared markers of inflammation and oxidative stress in adolescents of different ethnicities. METHODS: This was a cross-sectional cohort study of healthy Caucasian (C), H, and AA adolescents. Fasting urine for F2-isoprostanes and plasma for adiponectin, soluble vascular cell adhesion molecule (s-VCAM 1), interleukins (ILs), and tumor necrosis factor-alpha were collected and analyzed. Insulin resistance was measured by homeostasis model assessment of insulin resistance (HOMA-IR). Multivariable regression analyses were used to assess the effect of the biomarkers on HOMA-IR. RESULTS: Seventy adolescents were enrolled (26 C, 20 A, and 24 H); 32 were male (46%) and 27 (39%) were obese. Exploratory analysis showed that for every 1 U increase in BMI z-score, IL-8 rose by 0.53 (0.05, 1.00), P = 0.03. On regression analyses, for every unit increase in BMI z-score, HOMA-IR increased by 0.67 U (P = 0.001); for every unit increase in IL-8, HOMA-IR decreased by 0.21 U (P = 0.04). None of the other biomarkers was significantly associated with HOMA-IR. CONCLUSIONS: Higher insulin resistance was associated with increasing BMI z-scores and lower IL-8. This pilot study demonstrates the need to further evaluate inflammatory markers as an independent risk factor for the development of diabetes and to explore if there is a cause and effect relationship between IL-8 and insulin resistance. This could prove valuable for early identification of insulin resistance and as targets for intervention. PMID- 26824678 TI - Reasoned versus reactive prediction of behaviour: a meta-analysis of the prototype willingness model. AB - The prototype willingness model (PWM) was designed to extend expectancy-value models of health behaviour by also including a heuristic, or social reactive pathway, to better explain health-risk behaviours in adolescents and young adults. The pathway includes prototype, i.e., images of a typical person who engages in a behaviour, and willingness to engage in behaviour. The current study describes a meta-analysis of predictive research using the PWM and explores the role of the heuristic pathway and intentions in predicting behaviour. Eighty-one studies met inclusion criteria. Overall, the PWM was supported and explained 20.5% of the variance in behaviour. Willingness explained 4.9% of the variance in behaviour over and above intention, although intention tended to be more strongly related to behaviour than was willingness. The strength of the PWM relationships tended to vary according to the behaviour being tested, with alcohol consumption being the behaviour best explained. Age was also an important moderator, and, as expected, PWM behaviour was best accounted for within adolescent samples. Results were heterogeneous even after moderators were taken into consideration. This meta analysis provides support for the PWM and may be used to inform future interventions that can be tailored for at-risk populations. PMID- 26824679 TI - Potentially inappropriate prescriptions in patients admitted to a psychiatric hospital. AB - Background Very little is known about the general appropriateness of prescribing for psychiatric patients. Aims To identify prevalence and types of potentially inappropriate prescribing (PIP) of psychotropic and somatic medications, to assess the severity of potential clinical consequences and to identify possible predictive factors of PIP in a sample of adult psychiatric in-patients. Methods A descriptive, cross-sectional design using medication reviews by clinical pharmacologists to identify PIP during a 3-month period. The setting was in patient units in a psychiatric department of a Danish university hospital during a 3-month period (September 2013-November 2013). Patients medication lists (n = 207) were reviewed at the time of admission and all identified PIPs were assessed for potential consequences by clinical pharmacologists. Results There were 349 PIP identified in 1291 prescriptions. The proportion of patients found to have at least one PIP was 123/207 (59%) and the proportions of patients with at least one PIP assessed to be potentially serious or fatal was 69/207 (33%) and 24/207 (12%), respectively. Interactions between drugs 125/207 (36%) and too high doses of drugs 56/207 (16%) were the most frequent PIP. Predictive factors for PIP were polypharmacy (>5 prescriptions) and having one or more somatic diagnoses. Conclusion PIP is common in psychiatric patients and potentially fatal. Particularly polypharmacy (>5 prescriptions) and concomitant somatic illness were associated with the probability of PIP. Improving the quality of prescribing might benefit from an interprofessional approach and thus better training of physicians and nurses is needed in order to minimize PIP. PMID- 26824681 TI - Pathogenesis of Taenia solium taeniasis and cysticercosis. AB - Taenia solium infections (taeniasis/cysticercosis) are a major scourge to most developing countries. Neurocysticercosis, the infection of the human nervous system by the cystic larvae of this parasite, has a protean array of clinical manifestations varying from entirely asymptomatic infections to aggressive, lethal courses. The diversity of clinical manifestations reflects a series of contributing factors which include the number, size and location of the invading parasites, and particularly the inflammatory response of the host. This manuscript reviews the different presentations of T. solium infections in the human host with a focus on the mechanisms or processes responsible for their clinical expression. PMID- 26824680 TI - Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates. AB - OBJECTIVE: Signal attenuation is a major problem facing intracortical sensors for chronic neuroprosthetic applications. Many studies suggest that failure is due to gliosis around the electrode tips, however, mechanical and material causes of failure are often overlooked. The purpose of this study was to investigate the factors contributing to progressive signal decline by using scanning electron microscopy (SEM) to visualize structural changes in chronically implanted arrays and histology to examine the tissue response at corresponding implant sites. APPROACH: We examined eight chronically implanted intracortical microelectrode arrays (MEAs) explanted from non-human primates at times ranging from 37 to 1051 days post-implant. We used SEM, in vivo neural recordings, and histology (GFAP, Iba-1, NeuN). Three MEAs that were never implanted were also imaged as controls. MAIN RESULTS: SEM revealed progressive corrosion of the platinum electrode tips and changes to the underlying silicon. The parylene insulation was prone to cracking and delamination, and in some instances the silicone elastomer also delaminated from the edges of the MEA. Substantial tissue encapsulation was observed and was often seen growing into defects in the platinum and parylene. These material defects became more common as the time in vivo increased. Histology at 37 and 1051 days post-implant showed gliosis, disruption of normal cortical architecture with minimal neuronal loss, and high Iba-1 reactivity, especially within the arachnoid and dura. Electrode tracts were either absent or barely visible in the cortex at 1051 days, but were seen in the fibrotic encapsulation material suggesting that the MEAs were lifted out of the brain. Neural recordings showed a progressive drop in impedance, signal amplitude, and viable channels over time. SIGNIFICANCE: These results provide evidence that signal loss in MEAs is truly multifactorial. Gliosis occurs in the first few months after implantation but does not prevent useful recordings for several years. Progressive meningeal fibrosis encapsulates and lifts MEAs out of the cortex while ongoing foreign body reactions lead to progressive degradation of the materials. Long-term impedance drops are due to the corrosion of platinum, cracking and delamination of parylene, and delamination of silicone elastomer. Oxygen radicals released by cells of the immune system likely mediate the degradation of these materials. Future MEA designs must address these problems through more durable insulation materials, more inert electrode alloys, and pharmacologic suppression of fibroblasts and leukocytes. PMID- 26824682 TI - Combined eating behaviors and overweight: Eating quickly, late evening meals, and skipping breakfast. AB - OBJECTIVE: Various eating behaviors have been linked with body weight management. However, combined effects of major eating behaviors are not fully understood. This study aimed to clarify the association of the combination of eating quickly (EQ), late evening meals (LEM), and skipping breakfast (SB) with being overweight. METHOD: A cross-sectional study with standardized questions for EQ, LEM, and SB was conducted. Stratified random sampling of 5% of residents aged 20 to 80years was surveyed in a city in northeast Japan in 2011, and 4249 (84.9%) residents were analyzed. Association of combinations of eating behaviors on being overweight (BMI (kg/m(2)>=25.0)) was estimated by using logistic analysis, and odds ratio (OR) and 95% confidential interval were calculated after adjustment for potential covariates. RESULTS: LEM, SB, or a combination of LEM and SB was not significantly associated with being overweight. However, the combination of EQ or only EQ was significantly associated with being overweight. As the number of eating behavior practices increased, there was a linear increase in OR for being overweight. The OR of all three combined eating behaviors was higher than that of any combined two behaviors or of each behavior. DISCUSSION: This study result supports the evidence that EQ increases the risk of being overweight whether by itself or in combinations with LEM and/or SB. However, only LEM or only SB did not increase the risk of being overweight. PMID- 26824683 TI - Clinical utility of the Wechsler Memory Scale - Fourth Edition (WMS-IV) in patients with intractable temporal lobe epilepsy. AB - INTRODUCTION: The Wechsler Memory Scale (WMS) is one of the most widely used test batteries to assess memory functions in patients with brain dysfunctions of different etiologies. This study examined the clinical validation of the Dutch Wechsler Memory Scale - Fourth Edition (WMS-IV-NL) in patients with temporal lobe epilepsy (TLE). METHOD: The sample consisted of 75 patients with intractable TLE, who were eligible for epilepsy surgery, and 77 demographically matched healthy controls. All participants were examined with the WMS-IV-NL. RESULTS: Patients with TLE performed significantly worse than healthy controls on all WMS-IV-NL indices and subtests (p<.01), with the exception of the Visual Working Memory Index including its contributing subtests, as well as the subtests Logical Memory I, Verbal Paired Associates I, and Designs II. In addition, patients with mesiotemporal abnormalities performed significantly worse than patients with lateral temporal abnormalities on the subtests Logical Memory I and Designs II and all the indices (p<.05), with the exception of the Auditory Memory Index and Visual Working Memory Index. Patients with either a left or a right temporal focus performed equally on all WMS-IV-NL indices and subtests (F(15, 50)=.70, p=.78), as well as the Auditory-Visual discrepancy score (t(64)=-1.40, p=.17). CONCLUSION: The WMS-IV-NL is capable of detecting memory problems in patients with TLE, indicating that it is a sufficiently valid memory battery. Furthermore, the findings support previous research showing that the WMS-IV has limited value in identifying material-specific memory deficits in presurgical patients with TLE. PMID- 26824684 TI - Are All Stroke Patients Eligible for Fast Alteplase Treatment? An Analysis of Unavoidable Delays. AB - OBJECTIVES: The National Quality Forum recently endorsed a performance measure for time to intravenous thrombolytic therapy which allows exclusions for circumstances in which fast alteplase treatment may not be possible. However, the frequency and impact of unavoidable patient reasons for long door-to-needle time (DNT), such as need for medical stabilization, are largely unknown in clinical practice. As part of the Hurry Acute Stroke Treatment and Evaluation-2 (HASTE-2) project, we sought to identify patient and systems reasons associated with longer DNT. METHODS: From June 2012 to June 2013 we collected data on DNT and potential reasons for delays from 102 consecutive patients presenting directly to the emergency department who were treated with alteplase within 4.5 hours of symptom onset. RESULTS: Mean age was 71 years, 56/113 (54%) were women, median NIH Stroke Scale score was 13, and median DNT was 53 minutes. Potential delays were noted in 59/102 (58%), of which 31/102 (31%) were unavoidable patient-related or eligibility reasons. Median DNT was longer when patient-related or eligibility reasons for delay were present (60 minutes) than when absent (45 minutes, p = 0.005). Multivariable modeling showed that need for urgent medical stabilization, presentation with seizure and inability to confirm eligibility were associated with 35%-50% longer DNT times. CONCLUSIONS: Up to 31% of patients have delays due to medical or eligibility-related causes that may be legitimate reasons for providing alteplase later than the benchmark time of 60 minutes. PMID- 26824686 TI - Effect of organic molecular weight on mineralization and energy consumption of humic acid by H2O2/UV oxidation. AB - In this study, the effect of molecular weights (MWs) on mineralization, energy consumption, kinetic reaction, and trihalomethane formation potential (THMFP) of humic acid was evaluated by the process of H2O2/UV oxidation. Three ranges of MWs of 100 k-10 kDa (sample A), 10 k-1 kDa (sample B), and less than 1 kDa (sample C) were investigated. The results showed that the reaction constant k increased with either increased UV intensity or increased H2O2 dose; the order of k was kA > kB > kC, for all UV intensities from 16 to 64 W and H2O2 dose from 25 to 100 mg L( 1). In terms of EEO and EEM, the energy consumption decreased as the H2O2 dose increased with the descending order of sample C > sample B > sample A. The three samples had an initial dissolved organic carbon (DOC) of 20 mg L(-1) with the related values of THMFP of 325, 359, and 468 MUg L(-1) for samples A, B, and C, respectively. After H2O2/UV oxidation, the combination of a higher UV power with a shorter time was a better treatment condition for samples A and B as residual DOC and THMFP were smaller. PMID- 26824685 TI - Chlorogenic acid ameliorates intestinal mitochondrial injury by increasing antioxidant effects and activity of respiratory complexes. AB - Dietary polyphenols are thought to be beneficial for human health by acting as antioxidants. Chlorogenic acid (CGA) is abundant in plant-based foods as an ester of caffeic acid and quinic acid. In this study, we investigated the effects of CGA on mitochondrial protection. Our results demonstrated that pretreatment with CGA ameliorated the intestinal mitochondrial injury induced by H2O2; membrane potential was increased, mitochondrial swelling, levels of reactive oxygen species, contents of 8-hydroxy-2-deoxyguanosine, and cytochrome c released were decreased. The beneficial effects of CGA were accompanied by an increase in antioxidant and respiratory-chain complex I, IV, and V activities. In trinitrobenzene-sulfonic acid-induced colitic rats indicated that CGA supplementation improved mitochondria ultrastructure and decreased mitochondrial injury. Our results suggest a promising role for CGA as a mitochondria-targeted antioxidant in combating intestinal oxidative injury. Daily intake of diets containing CGA, such as coffee and honeysuckle, may be useful for prevention of intestinal diseases. PMID- 26824687 TI - Theoretical Modeling of the Ligand-Tuning Effect over the Transition Temperature in Four-Coordinated Fe(II) Molecules. AB - Spin-crossover molecules are systems of great interest due to their behavior as molecular level switches, which makes them promising candidates for nanoscale memory devices, among other applications. In this paper, we report a computational study for the calculation of the transition temperature (T(1/2)), a key physical quantity in the characterization of spin-crossover systems, for the family of tetracoordinated Fe(II) transition-metal complexes of generic formula [PhB(MesIm)3FeNPR1R2R3]. Our calculations correctly reproduce the experimentally reported decrease in the T(1/2) with an increasing size of the phosphine and allow for the prediction of the T(1/2) in new members of the family that are not reported so far. More importantly, further insight into the factors that control the fine-tuning of the T(1/2) can be obtained by direct analysis of the underlying electronic structure in terms of the relevant molecular orbitals. PMID- 26824688 TI - New Approach to Develop Optimized Sunscreens that Enable Cutaneous Vitamin D Formation with Minimal Erythema Risk. AB - Sunscreens protect the skin against erythemal radiation (Eer). But at the same time they reduce the effective radiation dose (EVD) responsible for the formation of previtamin D in the skin. The paper describes a calculation method for optimizing the ratio EVD/Eer behind sunscreens e.g. with SPF 5, 15 and 30 respectively. Taking into account that a majority of people in industrialized countries suffer from a shortage in vitamin D even in summer time, the ratio Evd/Eer is a new and important criterion for the quality of sunscreens. Furthermore the exposure time tvd needed per day for forming the equivalent of the recommended amount of 2000 IU of vitamin D per day for skin type 2 is estimated when sunscreens with different filter compositions are used. In vitro experiments show a significant increase of the conversion of 7-dehydrocholesterol (7-DHC) to previtamin D when exposed to artificial solar radiation behind an experimental sunscreen optimized for previtamin D production compared to a commercial sunscreen having the same SPF. PMID- 26824689 TI - Carbazole-pyranocoumarin conjugate and two carbazole alkaloids from the stems of Clausena excavata. AB - A carbazole-pyranocoumarin conjugate, carbazomarin B (1), and two carbazole alkaloids, 6-methoxymukonidine (2) and 2-hydroxy-3-methoxycarbazole (3), together with 27 known compounds (4-30), were isolated from the stems of Clausena excavata. Their structures have been elucidated by spectroscopic analyses. Compound 2 showed moderate cytotoxicity to HuCCA-1, MOLT-3 and HepG2 cancer cell lines with IC50 values of 15.09-28.50 MUg/mL, but none to A549 cell line. Heptaphylline (6) and nordentatin (23) were found to show moderate cytotoxic activity against HepG2 cell line with IC50 values of 12.33 and 11.33, respectively, while clausine K (27) exhibited strong cytotoxicity with IC50 value of 1.05 MUg/mL, better than a standard drug (etoposide, IC50 13.40 MUg/mL). PMID- 26824690 TI - Editorial. PMID- 26824691 TI - Relationships among depression, anxiety, anxiety sensitivity, and perceived social support in adolescents with conversion disorder. AB - OBJECTIVE: This study aimed to assess the relationships of depression, anxiety, anxiety sensitivity, and perceived social support with conversion symptoms in adolescents with conversion disorder (CD). METHODS: Fifty outpatients, aged 8-18 years, who had been diagnosed with CD and members of a control group were assessed using the psychological questionnaires. RESULTS: Compared with controls, adolescents with CD scored higher on the Child Depression Inventory (CDI), Screen for Child Anxiety-related Emotional Disorders (SCARED), Childhood Anxiety Sensitivity Index (CASI) total, CASI physical and cognitive subscales, and Multidimensional Scale of Perceived Social Support family subscale. Multiple regression analysis showed that CDI, CASI total, and CASI cognitive scores predicted the Somatoform Dissociation Questionnaire (SDQ) scores and that CDI and CASI total scores predicted the Children's Somatization Inventory (CSI) scores of subjects. CONCLUSIONS: This study suggest that adolescents with CD had poor psychosocial well-being, and depression, global anxiety sensitivity and anxiety sensitivity cognitive concerns are related to conversion symptoms. PMID- 26824692 TI - Biphenalenylidene: Isolation and Characterization of the Reactive Intermediate on the Decomposition Pathway of Phenalenyl Radical. AB - First isolation and characterization of biphenalenylidenes, which have long been unidentified reactive intermediates on the decomposition pathway of phenalenyl radical, were accomplished. Photoinduced electrocyclic ring-opening reaction of anti-dihydroperopyrene resulted in a successful conversion to E biphenalenylidene, which enabled a detailed investigation of the electronic structure of E-biphenalenylidene by means of spectroscopic techniques. A stereoisomer, Z-biphenalenylidene, was also observed by suppressing a facile E-Z isomerization to E-biphenalenylidene in a rigid matrix. Furthermore, Z biphenalenylidene demonstrated a thermal ring-closure in conrotatory process, which is not conforming to the Woodward-Hoffmann rule. These unusual reactivities of biphenalenylidene are ascribed to the ground states destabilized by its singlet biradical character, which was fully supported by theoretical calculations. The presence of E-biphenalenylidene on the decomposition pathway of phenalenyl was confirmed experimentally, leading to the full understanding of the decomposition mechanism of phenalenyl. PMID- 26824693 TI - Visual Acuity Testing: Feedback Affects Neither Outcome nor Reproducibility, but Leaves Participants Happier. AB - Assessment of visual acuity is a well standardized procedure at least for expert opinions and clinical trials. It is often recommended not giving patients feedback on the correctness of their responses. As this viewpoint has not been quantitatively examined so far, we quantitatively assessed possible effects of feedback on visual acuity testing. In 40 normal participants we presented Landolt Cs in 8 orientations using the automated Freiburg Acuity Test (FrACT, 0.5). The comfort ranking clearly differed, by 2 steps on the Likert scale: the condition (A)-no feedback-was on average "slightly uncomfortable", the other three conditions were "slightly comfortable" (p<0.0001). Feedback affected neither reproducibility nor the acuity outcome to any relevant extent. The participants, however, reported markedly greater comfort with any kind of feedback. We conclude that systematic feedback (as implemented in FrACT) offers nothing but advantages for routine use. PMID- 26824695 TI - Benefit Cost Analysis of Three Skin Cancer Public Education Mass-Media Campaigns Implemented in New South Wales, Australia. AB - Public education mass media campaigns are an important intervention for influencing behaviour modifications. However, evidence on the effectiveness of such campaigns to encourage the population to reduce sun exposure is limited. This study investigates the benefits and costs of three skin cancer campaigns implemented in New South Wales from 2006-2013. This analysis uses Australian dollars (AUD) and 2010-11 as the currency and base year, respectively. Historical data on skin cancer were used to project skin cancer rates for the period 2006 2020. The expected number of skin cancer cases is derived by combining skin cancer rates, sunburn rates and relative risk of skin cancers due to sun exposure. Counterfactual estimates are based on sunburn exposure in the absence of the campaigns. Monetary values are attached to direct (treatment) and indirect (productivity) costs saved due to fewer skin cancer cases. Monetary benefits are compared with the cost of implementing the campaigns and are presented in the form of a benefit-cost ratio. Relative to the counterfactual (i.e., no campaigns) there are an estimated 13,174 fewer skin cancers and 112 averted deaths over the period 2006-2013. The net present value of these benefits is $60.17 million and the campaign cost is $15.63 million. The benefit cost ratio is 3.85, suggesting that for every $1 invested a return of $3.85 is achieved. Skin cancer public education mass media campaigns are a good investment given the likely extent to which they reduce the morbidity, mortality and economic burden of skin cancer. PMID- 26824694 TI - Characterization of SCF-Complex during Bovine Preimplantation Development. AB - The degradation of maternal proteins is one of the most important events during early development, and it is presumed to be essential for embryonic genome activation (EGA), but the precise mechanism is still not known. It is thought that a large proportion of the degradation of maternal proteins is mediated by the ubiquitin-proteolytic system. In this study we focused on the expression of the Skp1-Cullin1-F-box (SCF) complex, a modular RING-type E3 ubiquitin-ligase, during bovine preimplantation development. The complex consists of three invariable components--Cul1, Skp1, Rbx1 and F-box protein, which determines the substrate specificity. The protein level and mRNA expression of all three invariable members were determined. Cul1 and Skp1 mRNA synthesis was activated at early embryonic stages, at the 4c and early 8c stage, respectively, which suggests that these transcripts are necessary for preparing the embryo for EGA. CUL1 protein level increased from MII to the morula stage, with a significant difference between MII and L8c, and between MII and the morula. The CUL1 protein was localized primarily to nuclei and to a lesser extent to the cytoplasm, with a lower signal in the inner cell mass (ICM) compared to the trophectoderm (TE) at the blastocyst stage. The level of SKP1 protein significantly increased from MII oocytes to 4c embryos, but then significantly decreased again. The localization of the SKP1 protein was analysed throughout the cell and similarly to CUL1 at the blastocyst stage, the staining was less intensive in the ICM. There were no statistical differences in RBX1 protein level and localization. The active SCF complex, which is determined by the interaction of Cul1 and Skp1, was found throughout the whole embryo during preimplantation development, but there was a difference at the blastocyst stage, which exhibits a much stronger signal in the TE than in the ICM. These results suggest that all these genes could play an important role during preimplantation development. This paper reveals comprehensive expression profile, the basic but important knowledge necessary for further studying. PMID- 26824696 TI - The UK Functional Assessment Measure (UK FIM+FAM): Psychometric Evaluation in Patients Undergoing Specialist Rehabilitation following a Stroke from the National UK Clinical Dataset. AB - The UK Functional Assessment Measure (UKFIM+FAM) is the principal outcome measure for the UK Rehabilitation Outcomes Collaborative (UKROC) national database for specialist rehabilitation. Previously validated in a mixed neurorehabilitation cohort, this study is the first to explore its psychometric properties in a stroke population, and compare left and right hemispheric strokes (LHS vs RHS). We analysed in-patient episode data from 62 specialist rehabilitation units collated through the UKROC database 2010-2013. Complete data were analysed for 1,539 stroke patients (LHS: 588, RHS: 566 with clear localisation). For factor analysis, admission and discharge data were pooled and randomised into two equivalent samples; the first for exploratory factor analysis (EFA) using principal components analysis, and the second for confirmatory factor analysis (CFA). Responsiveness for each subject (change from admission to discharge) was examined using paired t-tests and differences between LHS and RHS for the entire group were examined using non-paired t-tests. EFA showed a strong general factor accounting for >48% of the total variance. A three-factor solution comprising motor, communication and psychosocial subscales, accounting for >69% total variance, provided acceptable fit statistics on CFA (Root Mean Square Error of Approximation was 0.08 and Comparative Fit Index/ Tucker Lewis Index 0.922/0.907). All three subscales showed significant improvement between admission and discharge (p<0.001) with moderate effect sizes (>0.5). Total scores between LHS and RHS were not significantly different. However, LHS showed significantly higher motor scores (Mean 5.7, 95%CI 2.7, 8.6 p<0.001), while LHS had significantly lower cognitive scores, primarily in the communication domain ( 6.8 95%CI -7.7, -5.8 p<0.001). To conclude, the UK FIM+FAM has a three-factor structure in stroke, similar to the general neurorehabilitation population. It is responsive to change during in-patient rehabilitation, and distinguishes between LHS and RHS. This tool extends stroke outcome measurement beyond physical disability to include cognitive, communication and psychosocial function. PMID- 26824697 TI - Sarglaperoxides A and B, Sesquiterpene-Normonoterpene Conjugates with a Peroxide Bridge from the Seeds of Sarcandra glabra. AB - Sarglaperoxides A (1) and B (2), a pair of unusual sesquiterpene-normonoterpene conjugates with a peroxide bridge, were isolated from the seeds of Sarcandra glabra. The structures and absolute configurations of 1 and 2 were determined on the basis of spectroscopic data analysis, including MS, NMR, CD, and XRD. The two compounds were screened in antimicrobial, anti-inflammatory, and cytotoxic bioassays and showed moderate bioactivities. PMID- 26824698 TI - Region-Specific Defects of Respiratory Capacities in the Ndufs4(KO) Mouse Brain. AB - BACKGROUND: Lack of NDUFS4, a subunit of mitochondrial complex I (NADH:ubiquinone oxidoreductase), causes Leigh syndrome (LS), a progressive encephalomyopathy. Knocking out Ndufs4, either systemically or in brain only, elicits LS in mice. In patients as well as in KO mice distinct regions of the brain degenerate while surrounding tissue survives despite systemic complex I dysfunction. For the understanding of disease etiology and ultimately for the development of rationale treatments for LS, it appears important to uncover the mechanisms that govern focal neurodegeneration. RESULTS: Here we used the Ndufs4(KO) mouse to investigate whether regional and temporal differences in respiratory capacity of the brain could be correlated with neurodegeneration. In the KO the respiratory capacity of synaptosomes from the degeneration prone regions olfactory bulb, brainstem and cerebellum was significantly decreased. The difference was measurable even before the onset of neurological symptoms. Furthermore, neither compensating nor exacerbating changes in glycolytic capacity of the synaptosomes were found. By contrast, the KO retained near normal levels of synaptosomal respiration in the degeneration-resistant/resilient "rest" of the brain. We also investigated non-synaptic mitochondria. The KO expectedly had diminished capacity for oxidative phosphorylation (state 3 respiration) with complex I dependent substrate combinations pyruvate/malate and glutamate/malate but surprisingly had normal activity with alpha-ketoglutarate/malate. No correlation between oxidative phosphorylation (pyruvate/malate driven state 3 respiration) and neurodegeneration was found: Notably, state 3 remained constant in the KO while in controls it tended to increase with time leading to significant differences between the genotypes in older mice in both vulnerable and resilient brain regions. Neither regional ROS damage, measured as HNE-modified protein, nor regional complex I stability, assessed by blue native gels, could explain regional neurodegeneration. CONCLUSION: Our data suggests that locally insufficient respiration capacity of the nerve terminals may drive focal neurodegeneration. PMID- 26824699 TI - Prognostic Value of Basic Fibroblast Growth Factor (bFGF) in Lung Cancer: A Systematic Review with Meta-Analysis. AB - BACKGROUND: Basic fibroblast growth factor (bFGF) is known to stimulate angiogenesis and thus to influence the proliferation, migration and survival of tumor cells. Many studies examined the relationship between human bFGF overexpression and survival in lung cancer patients, but the results have been mixed. To systematically summarize the clinical prognostic function of bFGF in lung cancer, we performed this systematic review with meta-analysis. METHOD: Studies were identified by an electronic search of PubMed, EMBASE, China National Knowledge Infrastructure and Wanfang databases, including publications prior to August 2014. Pooled hazard ratios (HR) for overall survival (OS) were aggregated and quantitatively analyzed by meta-analysis. RESULTS: Twenty-two studies (n = 2154) were evaluated in the meta-analysis. Combined HR suggested that bFGF overexpression had an adverse impact on survival of patients with lung cancer(HR = 1.202,95%CI, 1.022-1.382). Our subgroup analysis revealed that the combined HR evaluating bFGF expression on OS in operable non-small cell lung cancer (NSCLC) was 1.553 (95%CI, 1.120-1.986); the combined HR in small cell lung cancer (SCLC) was 1.667 (95%CI, 1.035-2.299). There was no significant impact of bFGF expression on survival in advanced NSCLC. CONCLUSION: This meta-analysis showed that bFGF overexpression is a potential indicator of worse prognosis for patients with operable NSCLC and SCLC, but is not associated with outcome in advanced NSCLC. The data suggests that high bFGF expression is highly related to poor prognosis. Nevertheless,more high-quality studies should be performed in order to provide additional evidence for the prognostic value of bFGF in lung cancer. PMID- 26824700 TI - A Familiar(ity) Problem: Assessing the Impact of Prerequisites and Content Familiarity on Student Learning. AB - Prerequisites are embedded in most STEM curricula. However, the assumption that the content presented in these courses will improve learning in later courses has not been verified. Because a direct comparison of performance between students with and without required prerequisites is logistically difficult to arrange in a randomized fashion, we developed a novel familiarity scale, and used this to determine whether concepts introduced in a prerequisite course improved student learning in a later course (in two biology disciplines). Exam questions in the latter courses were classified into three categories, based on the degree to which the tested concept had been taught in the prerequisite course. If content familiarity mattered, it would be expected that exam scores on topics covered in the prerequisite would be higher than scores on novel topics. We found this to be partially true for "Very Familiar" questions (concepts covered in depth in the prerequisite). However, scores for concepts only briefly discussed in the prerequisite ("Familiar") were indistinguishable from performance on topics that were "Not Familiar" (concepts only taught in the later course). These results imply that merely "covering" topics in a prerequisite course does not result in improved future performance, and that some topics may be able to removed from a course thereby freeing up class time. Our results may therefore support the implementation of student-centered teaching methods such as active learning, as the time-intensive nature of active learning has been cited as a barrier to its adoption. In addition, we propose that our familiarity system could be broadly utilized to aid in the assessment of the effectiveness of prerequisites. PMID- 26824701 TI - Neuropsychological Impairment and Its Association with Violence Risk in Japanese Forensic Psychiatric Patients: A Case-Control Study. AB - BACKGROUND: In Japan, the legislation directing treatment of offenders with psychiatric disorders was enacted in 2005. Neuropsychological impairment is highly related to functional outcomes in patients with psychiatric disorders, and several studies have suggested an association between neuropsychological impairment and violent behaviors. However, there have been no studies of neuropsychological impairment in forensic patients covered by the Japanese legislation. This study is designed to examine the neuropsychological characteristics of forensic patients in comparison to healthy controls and to assess the relationship between neuropsychological impairment and violence risk. METHODS: Seventy-one forensic patients with psychiatric disorders and 54 healthy controls (matched by age, gender, and education) were enrolled. The CogState Battery (CSB) consisting of eight cognitive domains, the Iowa Gambling Task (IGT) to test emotion-based decision making, and psychological measures of violence risk including psychopathy were used. RESULTS: Forensic patients exhibited poorer performances on all CSB subtests and the IGT than controls. For each group, partial correlational analyses indicated that poor IGT performance was related to psychopathy, especially antisocial behavior. In forensic patients, the CSB composite score was associated with risk factors for future violent behavior, including stress and noncompliance with remediation attempts. CONCLUSION: Forensic patients with psychiatric disorders exhibit a wide range of neuropsychological impairments, and these findings suggest that neuropsychological impairment may increase the risk of violent behavior. Therefore, the treatment of neuropsychological impairment in forensic patients with psychiatric disorders is necessary to improve functional outcomes as well as to prevent violence. PMID- 26824702 TI - Antimicrobial Resistance and Molecular Epidemiology of Escherichia coli Causing Bloodstream Infections in Three Hospitals in Shanghai, China. AB - Escherichia coli (E. coli) is one of the most frequent and lethal causes of bloodstream infections (BSIs). We carried out a retrospective multicenter study on antimicrobial resistance and phylogenetic background of clinical E. coli isolates recovered from bloodstream in three hospitals in Shanghai. E. coli isolates causing BSIs were consecutively collected between Sept 2013 and Sept 2014. Ninety isolates randomly selected (30 from each hospital) were enrolled in the study. Antimicrobial susceptibility testing was performed by disk diffusion. PCR was used to detect antimicrobial resistance genes coding for beta-lactamases (TEM, CTX-M, OXA, etc.), carbapenemases (IMP, VIM, KPC, NDM-1 and OXA-48), and phylogenetic groups. eBURST was applied for analysis of multi-locus sequence typing (MLST). The resistance rates for penicillins, second-generation cephalosporins, fluoroquinolone and tetracyclines were high (>60%). Sixty-one of the 90 (67.8%) strains enrolled produced ESBLs and no carbapenemases were found. Molecular analysis showed that CTX-M-15 (25/61), CTX-M-14 (18/61) and CTX-M-55 (9/61) were the most common ESBLs. Phylogenetic group B2 predominated (43.3%) and exhibited the highest rates of ESBLs production. ST131 (20/90) was the most common sequence type and almost assigned to phylogenetic group B2 (19/20). The following sequence types were ST405 (8/90) and ST69 (5/90). Among 61 ESBL producers isolates, B2 (26, 42.6%) and ST131 (18, 29.5%) were also the most common phylogenetic group and sequence type. Genetic diversity showed no evidence suggesting a spread of these antimicrobial resistant isolates in the three hospitals. In order to provide more comprehensive and reliable epidemiological information for preventing further dissemination, well-designed and continuous surveillance with more hospitals participating was important. PMID- 26824703 TI - Mutational randomness as conditional independence and the experimental vindication of mutational Lamarckism. AB - The Modern Synthesis enshrined natural selection as the driver of adaptive evolution mainly by eliminating competing explanations. One of the eliminated competitors was Lamarckism, particularly 'mutational Lamarckism', a hypothesis according to which mutations may be directed towards producing phenotypes that improve the performance of the organism in a particular environment. Contrary to this hypothesis, the Modern Synthesis' view claims that mutations are 'random', even though the precise meaning of the term was never formally explicated. Current evidence seemingly in favour of the existence of legitimate cases of mutational Lamarckism has revitalized interest to seek a clarification of the meaning of the term 'random' in this context. Herein we analyse previous definitions of random mutations and show that they are deficient in three ways: either they are too wide, or too narrow, or dyadic. We argue that the linguistic expression 'random mutation' refers to a triadic rather than a dyadic relationship, propose a new, formal and precise definition based on the probabilistic concept of conditional independence, and finally provide examples of its application. One important consequence of our analysis is that the genomic specificity of the mutational process is not a necessary condition for the existence of mutational Lamarckism. PMID- 26824704 TI - Towards Validation of a New Computerised Test of Goal Neglect: Preliminary Evidence from Clinical and Neuroimaging Pilot Studies. AB - OBJECTIVE: Goal neglect is a significant problem following brain injury, and is a target for rehabilitation. It is not yet known how neural activation might change to reflect rehabilitation gains. We developed a computerised multiple elements test (CMET), suitable for use in neuroimaging paradigms. DESIGN: Pilot correlational study and event-related fMRI study. METHODS: In Study 1, 18 adults with acquired brain injury were assessed using the CMET, other tests of goal neglect (Hotel Test; Modified Six Elements Test) and tests of reasoning. In Study 2, 12 healthy adults underwent fMRI, during which the CMET was administered under two conditions: self-generated switching and experimenter-prompted switching. RESULTS: Among the clinical sample, CMET performance was positively correlated with both the Hotel Test (r = 0.675, p = 0.003) and the Modified Six Elements Test (r = 0.568, p = 0.014), but not with other clinical or demographic measures. In the healthy sample, fMRI demonstrated significant activation in rostro-lateral prefrontal cortex in the self-generated condition compared with the prompted condition (peak 40, 44, 4; ZE = 4.25, p(FWEcorr) = 0.026). CONCLUSIONS: These pilot studies provide preliminary evidence towards the validation of the CMET as a measure of goal neglect. Future studies will aim to further establish its psychometric properties, and determine optimum pre- and post-rehabilitation fMRI paradigms. PMID- 26824705 TI - Drug delivery function of carboxymethyl-beta-cyclodextrin modified upconversion nanoparticles for adamantine phthalocyanine and their NIR-triggered cancer treatment. AB - Near-infrared (NIR) light triggered photodynamic therapy (PDT), based on upconversion nanoparticles (UCNPs), has attracted great attention because of its high tissue penetration and low photodamage to living organisms. However, most UCNPs cannot be stably dispersed in aqueous solution and cannot carry photosensitive drugs directly. Besides, UCNP mediated PDT is a fluorescence resonance energy transfer (FRET) process from the UCNPs to the attached photosensitive drugs. So the drug and UCNPs must be stably connected and close enough. In this manuscript, carboxymethyl-beta-cyclodextrin (COOH-beta-CD) was used to connect UCNPs and adamantine modified phthalocyanine (Ad-ZnPc) through a self-assembly process followed by a host-guest interaction. COOH-beta-CD can provide good water solubility of the system and short-distance linking between the UCNPs and Ad-ZnPc. Most importantly, the system has a strong NIR light triggered PDT activity toward cancer cells. PMID- 26824706 TI - Management and prognosis of malignant peripheral nerve sheath tumors: The experience of the French Sarcoma Group (GSF-GETO). AB - BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are a rare subtype of soft tissue sarcoma. They can arise in irradiated fields, in patients with type 1 neurofibromatosis (NF1), or sporadically. MPNST exhibit an aggressive behaviour, and their optimal management remains controversial. An unsolved issue is whether NF1-related and sporadic forms of MPNST have a different prognosis, and should be managed differently. MATERIAL AND METHODS: Adult and paediatric patients with histologically confirmed MPNST treated between 1990 and 2013 in French cancer centres of the GSF/GETO network, were included in this retrospective study. RESULTS: A total of 353 patients (37% with NF1 and 59% with sporadic tumours) were analysed. Median age at diagnosis was 42 years (range 1 94). The majority of tumours developed in the limbs, were deep-seated and of high grade. Two hundreds and ninety four patients underwent a curative intent surgery. Among them, 60 patients (21%) had neoadjuvant treatment (mainly chemotherapy), and 173 (59%) had adjuvant treatment (mainly radiotherapy). For operated patients, median progression free and overall survival (OS) were 26.3 months and 95.8 months, respectively. In multivariate analysis, poor-prognosis factors for OS were high grade, deep location, locally advanced stage at diagnosis, and macroscopically incomplete resection (R2). NF1 status was not negatively prognostic, except in the recurrence or metastatic setting, where NF1-related MPNST patients treated with palliative chemotherapy showed worse survival than patients with sporadic forms. CONCLUSION: To our knowledge, our series is the largest study of patients with MPNST reported to date. For operated patients, we showed a worse prognosis for NF1-related MPNST, due to different clinical features at diagnosis, more than NF1 status itself. The French sarcoma group is now conducting correlative analyses on these patients, using the latest molecular tools. PMID- 26824707 TI - Correction: Evaluating the Early Benefit of Quadrivalent HPV Vaccine on Genital Warts in Belgium: A Cohort Study. PMID- 26824708 TI - Carbon Nanotube Properties Influence Adsorption of Phenanthrene and Subsequent Bioavailability and Toxicity to Pseudokirchneriella subcapitata. AB - The bioavailability of organic contaminants adsorbed to carbon nanotubes (CNTs) remains unclear, especially in complex natural freshwaters containing natural organic matter (NOM). Here, we report on the adsorption capacity (Q(0)) of five CNTs exhibiting different physicochemical properties, including a single-walled CNT (SWCNTs), multiwalled CNTs (MWCNT-15 and MWCNT-30), and functionalized MWCNTs (hydroxyl, -OH, and carboxyl, -COOH), for the model polycyclic aromatic hydrocarbon phenanthrene (3.1-800 MUg/L). The influence of phenanthrene adsorption by the CNTs on bioavailability and toxicity was investigated using the freshwater algae Pseudokirchneriella subcapitata. CNTs were dispersed in algal growth media containing NOM (DOC, 8.77 mg/L; dispersed concentrations: 0.5, 1.3, 1.3, 3.3, and 6.1 mg/L for SWCNT, MWCNT-15, MWCNT-30, MWCNT-OH, and MWCNT-COOH, respectively). Adsorption isotherms of phenanthrene to the dispersed CNTs were fitted with the Dubinin-Ashtakhov model. Q(0) differed among the CNTs, increasing with increasing surface area and decreasing with surface functionalization. SWCNT and MWCNT-COOH exhibited the highest and lowest log Q(0) (8.891 and 7.636 MUg/kg, respectively). The presence of SWCNTs reduced phenanthrene toxicity to algae (EC50; 528.4) compared to phenanthrene-only (EC50; 438.3), and the presence of MWCNTs had no significant effect on phenanthrene toxicity. However, phenanthrene adsorbed to NOM-dispersed CNTs proved to be bioavailable and contribute to exert toxicity to P. subcapitata. PMID- 26824709 TI - Bioactive Components in Human Milk Along the First Month of Life: Effects of Iodine Supplementation during Pregnancy. AB - BACKGROUND/AIMS: Human milk is considered the most suitable food for infants. The potential benefits of breastfeeding can be explained by the presence of different growth and neurotrophic factors in human milk. This study was designed to detect some biomarkers in human milk, which could be involved in the infant neurodevelopment and in the regulation of the maturation of neonatal intestine (brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), glial fibrillary acidic protein (GFAP), fibroblast growth factor 21 (FGF21), lysophosphatidic acid (LPA) and autotaxin (ATX)), and compare them on the basis of the consumption of iodine supplements or multivitamins. METHODS: A prospective study included 37 healthy breastfeeding mothers, divided into 3 different groups: (1) 10 mothers who did not take supplements, (2) 17 mothers who took potassium iodine (KI) 200 ug/day and (3) 10 mothers who took a multivitamin supplement. RESULTS: The concentrations of BDNF, GDNF, GFAP, FGF21, LPA and ATX in human milk were not significantly different in women who took a multivitamin or KI supplement compared with those who did not take any supplement. CONCLUSIONS: The presence of neurotrophic factors in human milk is neither modified by the consumption of supplements nor by their type. PMID- 26824710 TI - Focal Epilepsy: MR Imaging of Nonhemodynamic Field Effects by Using a Phase cycled Stimulus-induced Rotary Saturation Approach with Spin-Lock Preparation. AB - Purpose To investigate whether nonhemodynamic resonant saturation effects can be detected in patients with focal epilepsy by using a phase-cycled stimulus-induced rotary saturation (PC-SIRS) approach with spin-lock (SL) preparation and whether they colocalize with the seizure onset zone and surface interictal epileptiform discharges (IED). Materials and Methods The study was approved by the local ethics committee, and all subjects gave written informed consent. Eight patients with focal epilepsy undergoing presurgical surface and intracranial electroencephalography (EEG) underwent magnetic resonance (MR) imaging at 3 T with a whole-brain PC-SIRS imaging sequence with alternating SL-on and SL-off and two-dimensional echo-planar readout. The power of the SL radiofrequency pulse was set to 120 Hz to sensitize the sequence to high gamma oscillations present in epileptogenic tissue. Phase cycling was applied to capture distributed current orientations. Voxel-wise subtraction of SL-off from SL-on images enabled the separation of T2* effects from rotary saturation effects. The topography of PC SIRS effects was compared with the seizure onset zone at intracranial EEG and with surface IED-related potentials. Bayesian statistics were used to test whether prior PC-SIRS information could improve IED source reconstruction. Results Nonhemodynamic resonant saturation effects ipsilateral to the seizure onset zone were detected in six of eight patients (concordance rate, 0.75; 95% confidence interval: 0.40, 0.94) by means of the PC-SIRS technique. They were concordant with IED surface negativity in seven of eight patients (0.88; 95% confidence interval: 0.51, 1.00). Including PC-SIRS as prior information improved the evidence of the standard EEG source models compared with the use of uninformed reconstructions (exceedance probability, 0.77 vs 0.12; Wilcoxon test of model evidence, P < .05). Nonhemodynamic resonant saturation effects resolved in patients with favorable postsurgical outcomes, but persisted in patients with postsurgical seizure recurrence. Conclusion Nonhemodynamic resonant saturation effects are detectable during interictal periods with the PC-SIRS approach in patients with epilepsy. The method may be useful for MR imaging-based detection of neuronal currents in a clinical environment. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 26824711 TI - Long-term Therapeutic Outcomes of Radiofrequency Ablation for Subcapsular versus Nonsubcapsular Hepatocellular Carcinoma: A Propensity Score Matched Study. AB - Purpose To compare the long-term therapeutic outcomes of radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) in subcapsular versus nonsubcapsular locations by using propensity score matching. Materials and Methods RF ablation for subcapsular HCC is controversial because of a high risk of incomplete ablation or major complications. This retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. Between April 2006 and December 2011, 508 consecutive patients (396 men, 112 women; age range, 30-80 years) with a single HCC (Barcelona Clinic Liver Cancer stage 0 or A) underwent ultrasonography-guided percutaneous RF ablation as a first-line treatment. The patients were divided into two groups according to tumor location: subcapsular (n = 227) and nonsubcapsular (n = 281). Subcapsular HCC was defined as an index tumor located within 0.1 cm of the liver capsule. The association of subcapsular location and therapeutic outcomes of RF ablation was evaluated, including (a) local tumor progression (LTP) by using a competing risk regression model and (b) overall survival (OS) by using a Cox proportional hazards model according to propensity score matched data. The major complication rates from both overall data and matched data were assessed. Results Matching yielded 163 matched pairs of patients. In the two matched groups, cumulative LTP rates were 18.8% and 20.9% at 3 and 5 years, respectively, in the subcapsular group and 13.2% and 16.0% in the nonsubcapsular group. Corresponding OS rates were 90.7% for 3 years and 83.2% for 5 years in the subcapsular group and 91.4% and 79.1%, respectively, in the nonsubcapsular group. Hazard ratios (HRs) for LTP (HR = 1.37, P = .244) and OS (HR = 0.86, P = .604) were not significantly different between the two matched groups. Additionally, differences in major complication rates were not significant between groups for the two sets of data (P > .05). Conclusion The differences in LTP, OS, and major complication rates of RF ablation for HCC were not significant between subcapsular and nonsubcapsular groups. ((c)) RSNA, 2016. PMID- 26824712 TI - Correlation between Dual-Energy and Perfusion CT in Patients with Hepatocellular Carcinoma. AB - Purpose To develop a dual-energy contrast media-enhanced computed tomographic (CT) protocol by using time-attenuation curves from previously acquired perfusion CT data and to evaluate prospectively the relationship between iodine enhancement metrics at dual-energy CT and perfusion CT parameters in patients with hepatocellular carcinoma (HCC). Materials and Methods Institutional review board and local ethics committee approval and written informed consent were obtained. The retrospective part of this study included the development of a dual-energy CT contrast-enhanced protocol to evaluate peak arterial enhancement of HCC in the liver on the basis of time-attenuation curves from previously acquired perfusion CT data in 20 patients. The prospective part of the study consisted of an intraindividual comparison of dual-energy CT and perfusion CT data in another 20 consecutive patients with HCC. Iodine density and iodine ratio (iodine attenuation of the lesion divided by iodine attenuation in the aorta) from dual energy CT and arterial perfusion (AP), portal venous perfusion, and total perfusion (TP) from perfusion CT were compared. Pearson R and linear correlation coefficients were calculated for AP and iodine density, AP and iodine ratio, TP and iodine density, and TP and iodine ratio. Results The dual-energy CT protocol consisted of bolus tracking in the abdominal aorta (threshold, 150 HU; scan delay, 9 seconds). The strongest intraindividual correlations in HCCs were found between iodine density and AP (r = 0.75, P = .0001). Moderate correlations were found between iodine ratio and AP (r = 0.50, P = .023) and between iodine density and TP (r = 0.56, P = .011). No further significant correlations were found. The volume CT dose index (11.4 mGy) and dose-length product (228.0 mGy . cm) of dual energy CT was lower than those of the arterial phase of perfusion CT (36.1 mGy and 682.3 mGy . cm, respectively). Conclusion A contrast-enhanced dual-energy CT protocol developed by using time-attenuation curves from previously acquired perfusion CT data sets in patients with HCC could show good correlation between iodine density from dual-energy CT with AP from perfusion CT. ((c)) RSNA, 2016. PMID- 26824713 TI - Acute Symptomatic Basilar Artery Stenosis: MR Imaging Predictors of Early Neurologic Deterioration and Long-term Outcomes. AB - Purpose To determine clinical, laboratory, and radiologic factors associated with early neurologic deterioration (END) and long-term outcomes in patients with medically treated symptomatic basilar artery stenosis (BAS). Materials and Methods The study design was approved by the institutional review board. From a database of all consecutive patients with cerebrovascular ischemia, the authors retrospectively included 292 patients with medically treated symptomatic BAS with at least 70% stenosis of the basilar artery. The authors evaluated various clinical factors, including National Institutes of Health Stroke Scale (NIHSS) score, C-reactive protein (CRP) level, fibrinogen level, and radiologic factors, including diffusion-weighted (DW) magnetic resonance (MR) imaging-based posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS), hyperintense basilar artery at fluid-attenuated inversion recovery (FLAIR) imaging (FLAIR hyperintense vessel [FHV]), and clot signs. The outcomes were defined as the development of END and with the 90-day modified Rankin Scale score (favorable score: 0-2). The authors performed a chi(2) test, followed by logistic regression analysis, to identify independent outcome predictors. Results The development of END was highly correlated with unfavorable 90-day modified Rankin Scale score (P < .001). The significant predictors for END were CRP level of at least 1.5 mg/dL (P < .001), NIHSS score of at least 4 (P = .002), pc-ASPECTS of 6 or less (P < .001), and proximal FHV (P = .022). Proximal FHV (P = .010), pc-ASPECTS of 6 or less (P = .002), brainstem involvement (P = .036), and NIHSS score of at least 4 (P < .001) were associated with an unfavorable 90-day modified Rankin Scale score. Neither aggressive medical treatment nor delayed intervention was associated with a favorable 90-day modified Rankin Scale score. Conclusion In medically treated symptomatic BAS, MR imaging parameters such as proximal basilar FHV and DW imaging-based pc-ASPECTS have independent prognostic values for END development and long-term outcomes. ((c)) RSNA, 2016. PMID- 26824714 TI - [Not Available]. PMID- 26824715 TI - Advances in Charge Displacement Analysis. AB - We define new general density-based descriptors for the quantification of charge transfer and polarization effects associated with the interaction between two fragments and the formation of a chemical bond. Our aim is to provide a simple yet accurate picture of a chemical interaction by condensing the information on the charge rearrangement accompanying it into a few chemically meaningful parameters. These charge displacement (CD) parameters quantify the total charge displaced upon bond formation and decompose it into a charge transfer component between the fragments and charge rearrangements taking place within the fragments. We then show how the new parameters can be easily calculated using the well-known CD function, which describes the charge flow along a chosen axis accompanying the formation of a bond. The approach presented here can be useful in a wide variety of contexts, ranging from weak interactions to electronic excitations to coordination chemistry. In particular, we discuss here how the scheme can be used for the characterization of the donation and back-donation components of metal-ligand bonds, in combination with the natural orbitals for chemical valence (NOCV) theory. In doing so, we discuss the interesting relationship between the proposed parameters and the corresponding NOCV eigenvalues, commonly used as a measure of the electron charge displacement associated with a given bonding contribution. As a prototype case study, we investigate the bond between a N-heterocyclic carbene and different metallic fragments. Finally, we show that our approach can be used in combination with the energy decomposition of the extended transition state method, providing an estimate of both charge transfer and polarization contributions to the interaction energy. PMID- 26824716 TI - Interplay of Tunneling, Two-State Reactivity, and Bell-Evans-Polanyi Effects in C H Activation by Nonheme Fe(IV)O Oxidants. AB - The study of C-H bond activation reactions by nonheme Fe(IV)O species with nine hydrocarbons shows that the kinetic isotope effect (KIE) involves strong tunneling and is a signature of the reactive spin states. Theory reproduces the observed spike-like appearance of plots of KIE(exp) against the C-H bond dissociation energy, and its origins are discussed. The experimentally observed Bell-Evans-Polanyi correlations, in the presence of strong tunneling, are reproduced, and the pattern is rationalized. PMID- 26824717 TI - Degeneration of stria vascularis in age-related hearing loss; a corrosion cast study in a mouse model. AB - Conclusion With age, in a mouse model, degenerative changes to the capillaries of the stria vascularis are observed. These range from a narrowing of vessel lumen to complete degeneration of strial vessels. Other vascular beds in the cochlea are relatively unchanged with age. Strial capillaries at the cochlear base are significantly more affected than those in mid-apical turns. Objectives Previous work suggests that age-related hearing loss is associated with degenerative changes to cochlear vasculature; the term strial presbyacusis is often cited. This study reports on vascular changes observed in a murine model of presbyacusis, analyzed using corrosion cast techniques. Methods A novel corrosion cast technique was developed to compare cochlear vasculature in control mice (non presbycusic, CD1) and old (> 6 months) C57BL/6 animals. ABR measures indicated a significant age-related threshold elevation in the C57BL/6 mice. Cochlear vascular casts were imaged using scanning electron microscopy, and vessel degeneration was quantified by measuring capillary diameters. Results Corrosion casts of cochlear vasculature in 6-12 month old C57BL/6 mice reveal significant degeneration of stria vascularis. Other capillary beds (spiral ligament and the spiral limbus) appear unchanged. Comparison of strial capillary diameters reveals significantly more damage in basal/lower-turn regions compared with the cochlear mid-turn. PMID- 26824718 TI - Highly Sensitive Two-Dimensional Paper Network Incorporating Biotin-Streptavidin for the Detection of Malaria. AB - Recently, two-dimensional paper networks have been developed to enable multistep assays to be performed in a lateral flow format. These devices have been used to perform simple enzyme linked immunoassays on paper. However, these devices have yet to incorporate more complex immunoassays, including the use of streptavidin biotin detection strategies. Here we present a modified two-dimensional paper network capable of consecutively delivering six reagents. The device requires only a single user step and delivers (i) the sample, (ii) the biotinylated detection antibody, (iii) streptavidin horseradish peroxidase, (iv) a wash buffer, (v) a colorimetric substrate, and (vi) a final wash buffer. To demonstrate the utility of this approach we designed an assay to detect the malaria protein Pf HRP2. Using this platform, we were able to achieve a limit-of detection equivalent to that of a traditional 96-well plate sandwich ELISA. In addition to improvements in the limit-of-detection, the inclusion of streptavidin biotin simplifies the development of similar tests for other targets. PMID- 26824719 TI - Self-Organization of Polystyrene-b-polyacrylic Acid (PS-b-PAA) Monolayer at the Air/Water Interface: A Process Driven by the Release of the Solvent Spreading. AB - We present an in situ structural study of the surface behavior of PS-b-PAA monolayers at the air/water interface at pH 2, for which the PAA blocks are neutral and using N,N-dimethyformamide (DMF) as spreading solvent. The surface pressure versus molecular area isotherm shows a perfectly reversible pseudoplateau over several cycles of compression/decompression. The width of such plateau enlarges when increasing temperature, conversely to what is classically observed in the case of an in-plane first order transition. We combined specular neutron reflectivity (SNR) experiments with contrast variation to solve the profile of each block perpendicular to the surface with grazing-incidence small angle scattering (GISAXS) measurements to determine the in-plane structure of the layer. SNR experiments showed that both PS and PAA blocks remain adsorbed on the surface for all surface pressure probed. A correlation peak at Q(xy)* = 0.021 A( 1) is evidenced by GISAXS at very low surface pressure which intensity first increases on the plateau. When compressing further, its intensity decays while Q(xy)* is shifted toward low Q(xy). The peak fully disappears at the end of the plateau. These results are interpreted by the formation of surface aggregates induced by DMF molecules at the surface. These DMF molecules remain adsorbed within the PS core of the aggregates. Upon compression, they are progressively expelled from the monolayer, which gives rise to the pseudoplateau on the isotherm. The intensity of the GISAXS correlation peak is set by the amount of DMF within the monolayer as it vanishes when all DMF molecules are expelled. This result emphizes the role of the solvent in Langmuir monolayer formed by amphiphilic copolymers which hydrophobic and hydrophilic parts are composed by long polymer chains. PMID- 26824720 TI - An overview of bacterial efflux pumps and computational approaches to study efflux pump inhibitors. AB - Micro-organisms express a wide range of transmembrane pumps known as multidrug efflux pumps that improve the micro-organism's ability to survive in severe environments and contribute to resistance against antibiotic and antimicrobial agents. There is significant interest in developing efflux inhibitors as an adjunct to treatment with current and next generation of antibiotics. A greater understanding of drug recognition and transport by multidrug efflux pumps is needed to develop clinically useful inhibitors, given the breadth of molecules that can be effluxed by these systems. We summarize some structural and functional data that could provide insights into the inhibition of transport mechanisms of these intricate molecular nanomachines with a focus on the advances in computational approaches. PMID- 26824721 TI - Nursing Students' Willingness to Care for Older Adults in Taiwan. AB - BACKGROUND: The possibilities that nurses will take care of persons 65 years of age or older in hospitals and communities are increasing due to a growing aged population. Nursing students should be prepared to face the challenges of their future practice. Therefore, factors associated with nursing students' willingness to care for older adults need to be identified. AIM: This study aimed to explore Taiwanese nursing students' willingness to work with older persons and factors associated with this. METHODS: A cross-sectional research design was used. Stratified sampling was applied to recruit participants from seven nursing schools in northern, central, southern, and eastern areas of Taiwan. There were 612 nursing students who successful completed the questionnaire including demographic data, the Attitudes Toward the Elderly Scale, and the Willingness Toward the Elderly Care Scale. Data were collected between November 2012 and January 2013. A stepwise regression analysis was conducted to identify predictors of nursing students' willingness to care for older adults. FINDINGS: The mean score of nursing students' attitudes toward older people was 73.86 (SD = 8.9), with a range of 44-106. The mean score on the willingness to care for older adults was 55.01 (SD = 6.4), with a range of 36-75. The length of time with older adults per week (r = 0.12, p = .003) and grandparents having served as caregivers during the students' childhood (t = -2.147, beta = .032) were both positively associated with the willingness to care for older adults. The best predictors of nursing students' willingness to care for older adults were students' attitudes toward older adults (beta = 0.38, p < .001), paying attention to issues related to older adults (beta = 0.24, p < .001), and having the experience of being a volunteer who served older people (beta = 0.10, p = .005), which explained 26.8% of the total variance. CONCLUSIONS: Taiwanese undergraduate nursing students had neutral to slightly favorable attitudes toward working with older adults. Nursing students' positive attitudes about older adults, paying attention to issues related to older adults, and having been a volunteer that served older people were predictors of their willingness to care for older persons. Appropriate and practical strategies should be developed for students in order to increase their preference for caring for older people. CLINICAL RELEVANCE: The findings of this study can provide information for faculty members and clinical preceptors for designing curricula and related activities or arranging practicum in the future. PMID- 26824722 TI - Combining Manual Lymph Drainage with Physical Exercise after Modified Radical Mastectomy Effectively Prevents Upper Limb Lymphedema. AB - OBJECTIVE: Upper limb lymphedema is a common complication after radical mastectomy in patients with breast cancer. In this study, we examined the efficacy of self-manual lymph drainage (MLD) after modified radical mastectomy for the prevention of upper limb lymphedema, scar formation, or shoulder joint dysfunction in breast cancer patients. METHODS: Breast cancer patients scheduled for modified radical mastectomy were randomly apportioned to undergo physical exercise only (PE group, the control; n = 500) or self-MLD as well as exercise (MLD group; n = 500) after surgery. In the PE group, patients started to undertake remedial exercises and progressive weight training after recovery from anesthesia. In the MLD group, in addition to receiving the same treatments as in the PE group, the patients were trained to perform self-MLD on the surgical incision for 10 min/session, 3 sessions/day, beginning after suture removal and incision closure (10 to 30 days after the surgery). Scar formation was evaluated at one week, and 1, 3, 6, and 12 months after the surgery, respectively. Upper limb circumference and shoulder abduction were measured 24 h before surgery, and at one week, and 1, 3, 6 and 12 months after the surgery. RESULTS: Compared to those in the PE group, patients in MLD group experienced significant improvements in scar contracture, shoulder abduction, and upper limb circumference. CONCLUSIONS: Self-MLD, in combination with physical exercise, is beneficial for breast cancer patients in preventing postmastectomy scar formation, upper limb lymphedema, and shoulder joint dysfunction. PMID- 26824724 TI - Highly Sensitive Colorimetric Cancer Cell Detection Based on Dual Signal Amplification. AB - Facile and efficient detection of cancer cells at their preclinical stages is one of the central challenges in cancer diagnostics. A direct, rapid, highly sensitive and specific biosensor for detection of cancer biomarkers is desirable in early diagnosis and prognosis of cancer. In this work, we developed, for the first time, an easy and intuitive dispersion-dominated colorimetric strategy for cancer cell detection based on combining multi-DNA released from an aptamer scaffold with cyclic enzymatic amplification, which was triggered by aptamer DNA conformational switch and demonstrated by non-cross-linking gold nanoparticles (Au NPs) aggregation. First, five kinds of messenger DNAs (mDNAs) were aligned on the cancer cell aptamers modified on magnetic beads (MBs) to form mDNAs-Apt-MBs biocompatible nanosensors. In the presence of target cells, the aptamer would bind to the receptors on the cell membranes, and mDNAs would be released, resulting in the first amplification that one biological binding event would cause the release of multiple kinds of mDNAs simultaneously. After magnetic separation, the released mDNAs were introduced into the cyclic enzymatic amplification to cleave more single strand DNA (ssDNA) fragments. Instead of modification of Au NPs, these fragments and mDNAs could be adsorbed on the surface of Au NPs to prevent particle aggregation and ensure the stability and color of solution in high salt environments. The linear response for HL-60 cells in a concentration range from 10 to 10(4) cells was obtained with a detection limit of four cells in buffer solution. Moreover, the feasibility of the proposed strategy was demonstrated in a diluted serum sample. This dual signal amplification method can be extended to other types of cancer cells, which has potential application in point-of-care cancer diagnosis. PMID- 26824723 TI - Core promoter-specific gene regulation: TATA box selectivity and Initiator dependent bi-directionality of serum response factor-activated transcription. AB - Gene-specific activation by enhancers involves their communication with the basal RNA polymerase II transcription machinery at the core promoter. Core promoters are diverse and may contain a variety of sequence elements such as the TATA box, the Initiator (INR), and the downstream promoter element (DPE) recognized, respectively, by the TATA-binding protein (TBP) and TBP-associated factors of the TFIID complex. Core promoter elements contribute to the gene selectivity of enhancers, and INR/DPE-specific enhancers and activators have been identified. Here, we identify a TATA box-selective activating sequence upstream of the human beta-actin (ACTB) gene that mediates serum response factor (SRF)-induced transcription from TATA-dependent but not INR-dependent promoters and requires the TATA-binding/bending activity of TBP, which is otherwise dispensable for transcription from a TATA-less promoter. The SRF-dependent ACTB sequence is stereospecific on TATA promoters but activates in an orientation-independent manner a composite TATA/INR-containing promoter. More generally, we show that SRF regulated genes of the actin/cytoskeleton/contractile family tend to have a TATA box. These results suggest distinct TATA-dependent and INR-dependent mechanisms of TFIID-mediated transcription in mammalian cells that are compatible with only certain stereospecific combinations of activators, and that a TBP-TATA binding mechanism is important for SRF activation of the actin/cytoskeleton-related gene family. PMID- 26824726 TI - A new non-invasive option for functional evaluation of the femoral artery: Three dimensional speckle-tracking echocardiography (from the MAGYAR-Healthy Study). PMID- 26824725 TI - Co-Feeding Transmission of the Ehrlichia muris-Like Agent to Mice (Mus musculus). AB - The Ehrlichia muris-like agent (EMLA) is a newly recognized human pathogen found in Wisconsin and Minnesota. Ecological investigations have implicated both the blacklegged tick, Ixodes scapularis, and the white-footed mouse, Peromyscus leucopus, as playing roles in the maintenance of EMLA in nature. The work presented here shows that I. scapularis is an efficient vector of EMLA in a laboratory mouse model, but that Dermacentor variabilis, another frequent human biting tick found in EMLA endemic areas, is not. Additionally, I. scapularis larvae are able to acquire EMLA through co-feeding with infected nymphs. As EMLA only persists in mouse blood for a relatively short period of time, co-feeding transmission may play an important role in the maintenance of EMLA in ticks, and subsequently may play a role in limiting the geographic distribution of this pathogen in areas where co-feeding of larvae and nymphs is less common. PMID- 26824727 TI - Shifts in the climate space of temperate cyprinid fishes due to climate change are coupled with altered body sizes and growth rates. AB - Predictions of species responses to climate change often focus on distribution shifts, although responses can also include shifts in body sizes and population demographics. Here, shifts in the distributional ranges ('climate space'), body sizes (as maximum theoretical body sizes, Linfinity) and growth rates (as rate at which Linfinity is reached, K) were predicted for five fishes of the Cyprinidae family in a temperate region over eight climate change projections. Great Britain was the model area, and the model species were Rutilus rutilus, Leuciscus leuciscus, Squalius cephalus, Gobio gobio and Abramis brama. Ensemble models predicted that the species' climate spaces would shift in all modelled projections, with the most drastic changes occurring under high emissions; all range centroids shifted in a north-westerly direction. Predicted climate space expanded for R. rutilus and A. brama, contracted for S. cephalus, and for L. leuciscus and G. gobio, expanded under low-emission scenarios but contracted under high emissions, suggesting the presence of some climate-distribution thresholds. For R. rutilus, A. brama, S. cephalus and G. gobio, shifts in their climate space were coupled with predicted shifts to significantly smaller maximum body sizes and/or faster growth rates, aligning strongly to aspects of temperature-body size theory. These predicted shifts in Linfinity and K had considerable consequences for size-at-age per species, suggesting substantial alterations in population age structures and abundances. Thus, when predicting climate change outcomes for species, outputs that couple shifts in climate space with altered body sizes and growth rates provide considerable insights into the population and community consequences, especially for species that cannot easily track their thermal niches. PMID- 26824728 TI - Investigation of the hydrodynamic response of cells in drop on demand piezoelectric inkjet nozzles. AB - Cell motion within a liquid suspension inside a piezoelectrically actuated, cylindrical inkjet printhead was studied using high speed imaging and a low depth of field setup. For each ejected droplet, a cell within the inkjet nozzle was observed to exhibit one of three possible behaviors which are termed: cell travel, cell ejection and cell reflection. Cell reflection is an undesirable phenomenon which may adversely affect an inkjet's capability in dispensing cells and a possible reason why it was previously reported that the rate of cells dispensed did not follow the expected Poisson distribution. Through the study of the cells motions, it was hypothesized that the rheological properties of the media in the cell suspension play an important role in influencing the cell behaviors exhibited. This was experimentally studied with the tracking of cells within the inkjet nozzle in a 10% w/v Ficoll PM400 cell suspension. The effect of cell reflection was eliminated using the higher density and viscosity Ficoll PM400 suspension. The presented work is the first in-depth study of the cell behaviors occurring within a piezoelectric inkjet nozzle during the printing process. The understanding of the hydrodynamics during a droplet ejection and its effect on the suspended cells are imperative towards achieving reliable cell dispensing for biofabrication applications. PMID- 26824729 TI - Dietary iron concentration influences serum concentrations of manganese in rats consuming organic or inorganic sources of manganese. AB - To determine the effects of dietary Fe concentration on Mn bioavailability in rats fed inorganic or organic Mn sources, fifty-four 22-d-old male rats were randomly assigned and fed a basal diet (2.63 mg Fe/kg) supplemented with 0 (low Fe (L-Fe)), 35 (adequate Fe (A-Fe)) or 175 (high Fe (H-Fe)) mg Fe/kg with 10 mg Mn/kg from MnSO4 or Mn-lysine chelate (MnLys). Tissues were harvested after 21 d of feeding. Serum Mn was greater (P<0.05) in MnLys rats than in MnSO4 rats, and in L-Fe rats than in A-Fe or H-Fe rats. Duodenal divalent metal transporter-1 (DMT1) mRNA was lower (P<0.05) in H-Fe rats than in A-Fe rats for the MnSO4 treatment; however, no significant difference was observed between them for MnLys. Liver DMT1 mRNA abundance was greater (P<0.05) in MnSO4 than in the MnLys group for H-Fe rats. The DMT1 protein in duodenum and liver and ferroportin 1 (FPN1) protein in liver was greater (P<0.05) in the MnSO4 group than in the MnLys group, and in L-Fe rats than in H-Fe rats. Duodenal FPN1 protein was greater (P<0.05) in L-Fe rats than in A-Fe rats for the MnLys treatment, but it was not different between them for the MnSO4 treatment. Results suggest that MnLys increased serum Mn concentration as compared with MnSO4 in rats irrespective of dietary Fe concentration, which was not because of the difference in DMT1 and FPN1 expression in the intestine and liver. PMID- 26824730 TI - Short-term effects of dietary advanced glycation end products in rats. AB - Dietary advanced glycation end products (AGE) formed during heating of food have gained interest as potential nutritional toxins with adverse effects on inflammation and glucose metabolism. In the present study, we investigated the short-term effects of high and low molecular weight (HMW and LMW) dietary AGE on insulin sensitivity, expression of the receptor for AGE (RAGE), the AGE receptor 1 (AGER1) and TNF-alpha, F2-isoprostaglandins, body composition and food intake. For 2 weeks, thirty-six Sprague-Dawley rats were fed a diet containing 20% milk powder with different proportions of this being given as heated milk powder (0, 40 or 100%), either native (HMW) or hydrolysed (LMW). Gene expression of RAGE and AGER1 in whole blood increased in the group receiving a high AGE LMW diet, which also had the highest urinary excretion of the AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1). Urinary excretion of N epsilon-carboxymethyl-lysine increased with increasing proportion of heat-treated milk powder in the HMW and LMW diets but was unrelated to gene expression. There was no difference in insulin sensitivity, F2-isoprostaglandins, food intake, water intake, body weight or body composition between the groups. In conclusion, RAGE and AGER1 expression can be influenced by a high AGE diet after only 2 weeks in proportion to MG-H1 excretion. No other short-term effects were observed. PMID- 26824731 TI - Modifying effects of maternal Hb concentration on infant birth weight in women receiving prenatal iron-containing supplements: a randomised controlled trial. AB - Concerns have been raised about the benefits of Fe-containing supplements on infant birth weight among women with normal/high Hb levels at baseline. Thus far, no clinical trials have examined whether the effects of prenatal Fe-containing supplements on birth weight vary by maternal Hb levels. We compared the effects of Fe-folic acid (IFA) or multiple micronutrients (MMN) with folic acid (FA) supplements on birth weight among pregnant women with mild/no anaemia or high Hb levels. A double-blind randomised controlled trial was conducted in 2006-2009. In total, 18 775 pregnant women with mild/no anaemia (145 g/l) baseline Hb levels, IFA and MMN supplements increased birth weight by 91.44 (95% CI 3.37, 179.51) g and 107.63 (95% CI 21.98, 193.28) g (P<0.05), respectively, compared with the FA group. No differences were found between the IFA and the MMN group, regardless of maternal Hb concentration. In conclusion, the effects of Fe-containing supplements on birth weight depended on baseline Hb concentrations. The Fe containing supplements improved birth weight in women with very high Hb levels before 20 weeks of gestation. PMID- 26824732 TI - Intake of essential fatty acids in Indonesian children: secondary analysis of data from a nationally representative survey. AB - Essential fatty acids (EFA) such as alpha-linolenic acid (ALA) and linoleic acid (LA) are needed for healthy growth and development of children. Worldwide, reliable intake data of EFA are often lacking. The objective of this study was to investigate dietary intake of EFA in Indonesian children. Dietary intake data of 4-12-year-old children (n 45,821) from a nationally representative Indonesian survey were used to estimate median intake and distribution of population fatty acid intake. Missing data on individual fatty acids in the Indonesian food composition table were complemented through chemical analyses of national representative food samples and imputation of data from the US nutrient database. Nutrient adequacy ratios were calculated as a percentage of FAO/WHO intake recommendations. The medians of total fat intake of the children was 26.7 (10th 90th percentile 11.2-40.0) percentage of total daily energy (%E). Intakes of fatty acids were 4.05 (10th-90th percentile 1.83-7.22) %E for total PUFA, 3.36 (10th-90th percentile 1.14-6.29) %E for LA and 0.20 (10th-90th percentile 0.07 0.66) %E for ALA. Median intake of PUFA was 67 % and that of ALA 40 % of the minimum amounts recommended by FAO/WHO. These data indicate that a majority of Indonesian children has intakes of PUFA and specifically ALA that are lower than recommended intake levels. Total fat and LA intakes may be suboptimal for a smaller yet considerable proportion of children. Public health initiatives should provide practical guidelines to promote consumption of PUFA-rich foods. PMID- 26824733 TI - Is there a mismatch between who gets iron supplementation and who needs it? A cross-sectional study of iron supplements, iron deficiency anaemia and socio economic status in Australia. AB - Fe deficiency anaemia (IDA) is more prevalent in lower socio-economic groups; however, little is known about who actually receives Fe supplements. This paper aims to determine whether the groups most likely to have IDA are the most likely to be taking Fe supplements. Logistic regression analysis was conducted using the cross-sectional, nationally representative National Nutrition and Physical Activity Survey and National Health Measures Survey. After adjusting for other factors, those whose main language spoken at home was not English had twice the odds of having IDA compared with those whose main language spoken at home was English (95% CI 1.00, 4.32). Those who were not in the labour force also had twice the odds of having IDA as those who were employed (95% CI 1.16, 3.41). Those in income quintile 1 had 3.7 times the odds of having IDA compared with those in income quintile 5 (95% CI 1.42, 9.63). Those whose main language spoken at home was not English were significantly less likely to take Fe supplements (P=0.002) than those whose main language spoken at home was English. There was no significant difference in the likelihood of taking Fe supplements between those who were not in the labour force and those who were employed (P=0.618); between those who were in income quintile 1 and in higher income quintiles; and between males and females (P=0.854), after adjusting for other factors. There is a mismatch between those who are most in need of Fe supplements and those who currently receive them. PMID- 26824734 TI - RPA1 expression in esophageal carcinoma and its influence on radiosensitivity of esophageal carcinoma TE-1 cells. AB - AIM: To determinate the RPA1 expression in esophageal carcinoma and the paired tumor-adjacent tissue, and to explore the influence of RPA1 on radiosensitivity of esophageal carcinoma TE-1 cells. METHODS: Firstly, the RPA1 expression of 40 cases esophageal carcinoma and their adjacent tissues were detected by immunohistochemistry. Secondly, The esophageal carcinoma cell subline-radiation resistance model (TE-1R) was constructed by radiation-induction, the RPA1 expression and proliferation activity of TE-1 and TE-1R cells were detected by Western blot and MTT assay respectively. After radiation, the expression of RPA1 and cell apoptosis were detected by Western blot and FACS respectively. Cell clone formation and survival rate were detected by clonogenic assay. Thirdly, Inhibiting RPA1 expression by siRNA in TE-1 cells, the expression of RPA1 was detected by RT-PCR and Western blot, Cell proliferation inhibition ratio and cell apoptosis after radiation were detected by MTT assay and FACS respectively. RESULTS: The RPA1 expression in esophageal carcinoma was significantly higher than that in the tumor-adjacent tissues, which was associated with tumor invasion and lymph node metastasis. The RPA1 expression in TE-1R cells was higher than that in TE-1 cells, while the proliferation activity of TE-1R cells was lower than that of TE-1 cells, and the apoptosis rate of TE-1R cells after radiation was less than that of TE-1 cells. In addtion, the clone formation and survival rate of TE-1R cells were higher than that of TE-1 cells. Moreover, inhibiting RPA1 expression by siRNA-RPA1 could promoted proliferation inhibition ratio and apoptosis rate of TE-1 cells after radiation. CONCLUSION: The over-expression of RPA1 in esophageal carcinoma was related with progression and metastasis. Moreover, radiation induced the excessive expression RPA1 in TE-1 cells, and the radiosensitivity of TE-1R cells was less than that of TE-1 cells. Furthermore, inhibiting RPA1 expression could increase radiosensitivity of TE-1 cells. Overall, RPA1 could influence radiosensitivity and might be one important mechanism of radiation resistance in TE-1 cells. PMID- 26824735 TI - L-arginine, apoptosis and gastric cancer: any role for Helicobacter pylori? PMID- 26824736 TI - Steroids and hiccup: an exceptional but disturbing association in ulcerative colitis not to overlook. PMID- 26824738 TI - Patients' perceptions of a chronic pain rehabilitation program: changing the conversation. AB - Objective Research supports the effectiveness of comprehensive approaches to chronic pain treatment, including behavioral management and physical reconditioning. However, less is known about patients' perceptions of this treatment approach. The current study evaluated patient perceptions and treatment outcomes utilizing both qualitative and quantitative data collection. Methods A total of 498 adult patients (>=18 years of age; Mage = 49.1) completed an intensive outpatient interdisciplinary chronic pain rehabilitation program, completed survey measures at admission and discharge, and were asked open-ended questions about their treatment experience at discharge. Results Patients reported significant decreases in pain severity, t(488) = 23.08, p < .001, and pain-related interference, t(488) = 24.28, p < .001, at discharge. Patients endorsed self-management strategies, particularly relaxation skills (85%), moderation and/or modification (47%), and exercise, stretching and/or physical therapy (39%) as the most important aspects of treatment. Conclusions Patients perceive behavioral skills to manage pain and physical reconditioning to be important components of a successful pain rehabilitation program. These findings can inform conversations with both physicians and patients about the importance of biopsychosocial approaches to pain management. Key limitations include a lack of racial/ethnic diversity, use of anonymous data that cannot be linked directly to patient outcomes, and reliance on self-report data. PMID- 26824737 TI - Differential Resting-State Functional Connectivity of Striatal Subregions in Bipolar Depression and Hypomania. AB - Bipolar disorder (BP) is characterized by periods of depression (BPD) and (hypo)mania (BPM), but the underlying state-related brain circuit abnormalities are not fully understood. Striatal functional activation and connectivity abnormalities have been noted in BP, but consistent findings have not been reported. To further elucidate striatal abnormalities in different BP states, this study investigated differences in resting-state functional connectivity of six striatal subregions in BPD, BPM, and healthy control (HC) subjects. Ninety medication-free subjects (30 BPD, 30 BPM, and 30 HC), closely matched for age and gender, were scanned using 3T functional magnetic resonance imaging (fMRI) acquired at resting state. Correlations of low-frequency blood oxygen level dependent signal fluctuations for six previously described striatal subregions were used to obtain connectivity maps of each subregion. Using a factorial design, main effects for differences between groups were obtained and post hoc pairwise group comparisons performed. BPD showed increased connectivity of the dorsal caudal putamen with somatosensory areas such as the insula and temporal gyrus. BPM group showed unique increased connectivity between left dorsal caudate and midbrain regions, as well as increased connectivity between ventral striatum inferior and thalamus. In addition, both BPD and BPM exhibited widespread functional connectivity abnormalities between striatal subregions and frontal cortices, limbic regions, and midbrain structures. In summary, BPD exhibited connectivity abnormalities of associative and somatosensory subregions of the putamen, while BPM exhibited connectivity abnormalities of associative and limbic caudate. Most other striatal subregion connectivity abnormalities were common to both groups and may be trait related. PMID- 26824739 TI - Design of Xylose-Based Semisynthetic Polyurethane Tissue Adhesives with Enhanced Bioactivity Properties. AB - Developing biocompatible tissue adhesives with high adhesion properties is a highly desired goal of the tissue engineering due to adverse effects of the sutures. Therefore, our work involves synthesis, characterization, adhesion properties, protein adsorption, in vitro biodegradation, in vitro and in vivo biocompatibility properties of xylose-based semisynthetic polyurethane (NPU-PEG X) bioadhesives. Xylose-based semisynthetic polyurethanes were developed by the reaction among 4,4'-methylenebis(cyclohexyl isocyanate) (MCI), xylose and polyethylene glycol 200 (PEG). Synthesized polyurethanes (PUs) showed good thermal stability and high adhesion strength. The highest values in adhesion strength were measured as 415.0 +/- 48.8 and 94.0 +/- 2.8 kPa for aluminum substrate and muscle tissue in 15% xylose containing PUs (NPU-PEG-X-15%), respectively. The biodegradation of NPU-PEG-X-15% was also determined as 19.96 +/ 1.04% after 8 weeks of incubation. Relative cell viability of xylose containing PU was above 86%. Moreover, 10% xylose containing NPU-PEG-X (NPU-PEG-X-10%) sample has favorable tissue response, and inflammatory reaction between 1 and 6 weeks implantation period. With high adhesiveness and biocompatibility properties, NPU-PEG-X can be used in the medical field as supporting materials for preventing the fluid leakage after abdominal surgery or wound closure. PMID- 26824740 TI - Multi-Locus Sequence Typing of Bartonella bacilliformis DNA Performed Directly from Blood of Patients with Oroya's Fever During a Peruvian Outbreak. AB - BACKGROUND: Bartonella bacilliformis is the etiological agent of Carrion's disease, a neglected tropical poverty-linked illness. This infection is endemic of Andean regions and it is estimated that approximately 1.7 million of South Americans are at risk. This bacterium is a fastidious slow growing microorganism, which is difficult and cumbersome to isolate from clinical sources, thereby hindering the availability of phylogenetic relationship of clinical samples. The aim of this study was to perform Multi Locus Sequence Typing of B. bacilliformis directly in blood from patients diagnosed with Oroya fever during an outbreak in Northern Peru. METHODOLOGY/PRINCIPAL FINDINGS: DNA extracted among blood samples from patients diagnosed with Oroya's fever were analyzed with MLST, with the amplification of 7 genetic loci (ftsZ, flaA, ribC, rnpB, rpoB, bvrR and groEL) and a phylogenetic analysis of the different Sequence Types (ST) was performed. A total of 4 different ST were identified. The most frequently found was ST1 present in 66% of samples. Additionally, two samples presented a new allelic profile, belonging to new STs (ST 9 and ST 10), which were closely related to ST1. CONCLUSIONS/SIGNIFICANCE: The present data demonstrate that B. bacilliformis MLST studies may be possible directly from blood samples, being a promising approach for epidemiological studies. During the outbreak the STs of B. bacilliformis were found to be heterogeneous, albeit closely related, probably reflecting the evolution from a common ancestor colonizing the area. Additional studies including new samples and areas are needed, in order to obtain better knowledge of phylogenetic scenario B. bacilliformis. PMID- 26824741 TI - Early Changes in QRS Frequency Following Cardiac Resynchronization Predict Hemodynamic Response in Left Bundle Branch Block Patients. AB - INTRODUCTION: QRS characteristics are the cornerstone of patient selection in cardiac resynchronization therapy (CRT) and the presence of left bundle branch block (LBBB) and baseline QRS >=150 milliseconds portends a good outcome. We previously showed that baseline QRS frequency analysis adds predictive value to LBBB alone and have hypothesized that a change in frequency characteristics following CRT may produce additional predictive value. METHODS: We examined the QRS frequency characteristics of 182 LBBB patients before and soon after CRT. Patients were assigned to responder and nonresponder groups. Responders were defined by a decrease in left ventricular end-systolic volume (LVESV) >=15% following CRT. We analyzed the QRS in ECG leads I, AVF, and V3 before and soon after CRT using the discrete Fourier transform algorithm. The percentage of total QRS power within discrete frequency intervals before and after CRT was calculated. The reduction in lead V3 power <10 Hz was the best indicator of response. RESULTS: Baseline QRS width was similar between the responders and nonresponders (162.2 +/- 17.2 milliseconds vs. 158 +/- 22.1 milliseconds, respectively; P = 0.180). Responders exhibited a greater reduction in QRS power <10 Hz (-17.0 +/- 11.9% vs. -6.6 +/- 12.5%; P < 0.001) and a significant AUC (0.743; P < 0.001). A >=8% decline in QRS power <10 Hz produced the best predictive values (PPV = 84%, NPV = 59%). Importantly, when patients with baseline QRS <150 milliseconds were compared, the AUC improved (0.892, P < 0.001). CONCLUSIONS: Successful CRT produces a significant reduction in QRS power below 10 Hz, particularly when baseline QRS <150 milliseconds. These results indicate that QRS frequency changes after CRT provide additional predictive value to QRS alone. PMID- 26824742 TI - Discovery of Potent and Highly Selective A2B Adenosine Receptor Antagonist Chemotypes. AB - Three novel families of A2B adenosine receptor antagonists were identified in the context of the structural exploration of the 3,4-dihydropyrimidin-2(1H)-one chemotype. The most appealing series contain imidazole, 1,2,4-triazole, or benzimidazole rings fused to the 2,3-positions of the parent diazinone core. The optimization process enabled identification of a highly potent (3.49 nM) A2B ligand that exhibits complete selectivity toward A1, A2A, and A3 receptors. The results of functional cAMP experiments confirmed the antagonistic behavior of representative ligands. The main SAR trends identified within the series were substantiated by a molecular modeling study based on a receptor-driven docking model constructed on the basis of the crystal structure of the human A2A receptor. PMID- 26824743 TI - TSLP Is a Potential Initiator of Collagen Synthesis and an Activator of CXCR4/SDF 1 Axis in Keloid Pathogenesis. AB - Recently, thymic stromal lymphopoietin (TSLP), which is well studied in allergic diseases, has been reported in fibrotic diseases, including idiopathic pulmonary fibrosis and atopic dermatitis fibrosis. However, the role of TSLP in keloid is obscure. In this study, we assessed the expression of TSLP in keloid tissue and investigated the possible role of TSLP in keloid pathogenesis. We observed that TSLP expression was increased in keloid tissue compared to normal tissue. Furthermore, TSLP treatment induced increased collagen I and collagen III expression in fibroblasts via transforming growth factor-?; however, there was higher expression in keloid fibroblasts compared to normal fibroblasts. Stromal cell-derived factor-1?, which was recently reported to enhance wound healing through recruiting bone marrow-derived mesenchymal stem cells to the wound area, increased after TSLP treatment in fibroblasts and was primarily expressed in ? smooth muscle action-positive myofibroblasts in keloid tissue. Furthermore, fibrocytes expressing CXCR4, a stromal cell-derived factor-1? receptor, were significantly increased in keloid tissue compared to normal tissue. Finally, intradermal TSLP injection on BALB/c mice increased stromal cell-derived factor 1? expression and CXCR4(+) fibrocytes infiltration. Our data suggest that TSLP is a potent inducer of collagen and transforming growth factor-? production in keloid fibroblasts. In addition, it might activate the CXCR4/stromal cell-derived factor-1 axis to increase fibrocyte infiltration into the keloid tissue. PMID- 26824745 TI - The Diabetic Foot: The Never-Ending Challenge. AB - Diabetes, a major public health concern, is increasing in prevalence worldwide. A diabetic patient has an up to 25% lifetime risk of developing a foot ulcer condition that predisposes that patient to lower-extremity amputation. The underlying pathology is diabetic peripheral neuropathy and peripheral arterial disease (PAD) associated with deformities of foot anatomy due to motor neuropathy. Trauma, often secondary to ill-fitting shoes, precipitates skin breakdown, whereas PAD determines the prognosis for healing. Whenever optimal offloading is guaranteed, a neuropathic ulcer will heal, whereas an ulceration compromised by even a minor degree of arterial insufficiency has little chance of healing without revascularization. The population presenting with diabetic foot ulcers has shown a clear shift from neuropathic ulcers to neuro-ischaemic ulcers over the last two decades, underscoring the necessity to adapt management strategies to this condition. Cohort studies (the Eurodiale study group) teach us that the underlying problems are an absence of assessment of PAD, underuse of imaging and late referral for revascularization. Regarding reducing amputation rates in diabetes, a highly preventable complication, the situation is far from being under control. Prevention strategies targeting the high-risk population to avoid ulcer recurrence, optimized management by multidisciplinary foot care teams, integrated care with a clear definition of the patient itinerary and anticipated action to ameliorate ischaemia are promising options for the future. PMID- 26824744 TI - Nipple Angiofibromas with Loss of TSC2 Are Associated with Tuberous Sclerosis Complex. PMID- 26824747 TI - Sustainable Cost Models for mHealth at Scale: Modeling Program Data from m4RH Tanzania. AB - BACKGROUND: There is increasing evidence that mobile phone health interventions ("mHealth") can improve health behaviors and outcomes and are critically important in low-resource, low-access settings. However, the majority of mHealth programs in developing countries fail to reach scale. One reason may be the challenge of developing financially sustainable programs. The goal of this paper is to explore strategies for mHealth program sustainability and develop cost recovery models for program implementers using 2014 operational program data from Mobile for Reproductive Health (m4RH), a national text-message (SMS) based health communication service in Tanzania. METHODS: We delineated 2014 m4RH program costs and considered three strategies for cost-recovery for the m4RH program: user pay for-service, SMS cost reduction, and strategic partnerships. These inputs were used to develop four different cost-recovery scenarios. The four scenarios leveraged strategic partnerships to reduce per-SMS program costs and create per SMS program revenue and varied the structure for user financial contribution. Finally, we conducted break-even and uncertainty analyses to evaluate the costs and revenues of these models at the 2014 user volume (125,320) and at any possible break-even volume. RESULTS: In three of four scenarios, costs exceeded revenue by $94,596, $34,443, and $84,571 at the 2014 user volume. However, these costs represented large reductions (54%, 83%, and 58%, respectively) from the 2014 program cost of $203,475. Scenario four, in which the lowest per-SMS rate ($0.01 per SMS) was negotiated and users paid for all m4RH SMS sent or received, achieved a $5,660 profit at the 2014 user volume. A Monte Carlo uncertainty analysis demonstrated that break-even points were driven by user volume rather than variations in program costs. CONCLUSIONS: These results reveal that breaking even was only probable when all SMS costs were transferred to users and the lowest per-SMS cost was negotiated with telecom partners. While this strategy was sustainable for the implementer, a central concern is that health information may not reach those who are too poor to pay, limiting the program's reach and impact. Incorporating strategies presented here may make mHealth programs more appealing to funders and investors but need further consideration to balance sustainability, scale, and impact. PMID- 26824746 TI - The Behavioral and Cognitive Executive Disorders of Stroke: The GREFEX Study. AB - BACKGROUND: Many studies have highlighted the high prevalence of executive disorders in stroke. However, major uncertainties remain due to use of variable and non-validated methods. The objectives of this study were: 1) to characterize the executive disorder profile in stroke using a standardized battery, validated diagnosis criteria of executive disorders and validated framework for the interpretation of neuropsychological data and 2) examine the sensitivity of the harmonization standards protocol proposed by the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) for the diagnosis of Vascular Cognitive Impairment. METHODS: 237 patients (infarct: 57; cerebral hemorrhage: 54; ruptured aneurysm of the anterior communicating artery (ACoA): 80; cerebral venous thrombosis (CVT): 46) were examined by using the GREFEX battery. The patients' test results were interpreted with a validated framework derived from normative data from 780 controls. RESULTS: Dysexecutive syndrome was observed in 88 (55.7%; 95%CI: 48-63.4) out of the 156 patients with full cognitive and behavioral data: 40 (45.5%) had combined behavioral and cognitive syndromes, 29 (33%) had a behavioral disorder alone and 19 (21.6%) had a cognitive syndrome alone. The dysexecutive profile was characterized by prominent impairments of initiation and generation in the cognitive domain and by hypoactivity with disinterest and anticipation loss in the behavioral domain. Cognitive impairment was more frequent (p = 0.014) in hemorrhage and behavioral disorders were more frequent (p = 0.004) in infarct and hemorrhage. The harmonization standards protocol underestimated (p = 0.007) executive disorders in CVT or ACoA. CONCLUSIONS: This profile of executive disorders implies that the assessment should include both cognitive tests and a validated inventory for behavioral dysexecutive syndrome. Initial assessment may be performed with a short cognitive battery, such as the harmonization standards protocol. However, administration of a full cognitive battery is required in selected patients. PMID- 26824748 TI - Ten-Year Experience with the Conservative Management of Abnormally Invasive, Residual Trophoblastic Disease. A Retrospective Case Series. AB - Conservative management of abnormally invasive, residual trophoblastic disease (AIRTD) is underreported. We aimed at critically reviewing our experience with such conservative management. We conducted a retrospective cohort study that included 24 women. The median completed week of gestation at delivery (20/24, 83.3%)/2nd trimester miscarriage (4/24, 16.7%) was 35 (range 17-41). Two women initially chose a surgical treatment (dilatation and curettage), but AIRTD remained sonographically visible afterward. Five patients developed a fever >38.0 degrees C for >=2 days (5/24, 20.8%). Due to heavy vaginal bleeding, 2 patients then underwent dilatation, diagnostic hysteroscopy, and curettage (2/24, 8.3%). One of these women also had to undergo hysterectomy (1/24, 4.2%). The 23 patients without hysterectomy underwent regular sonographic follow-up examinations. Regression of AIRTD was found after a median of 74 days (range 36-323). In conclusion, our data suggest that a conservative, observational treatment is feasible in AIRTD, with low rates of secondary surgical interventions. The long time intervals until regression require perseverance by these patients. PMID- 26824749 TI - Site-Specific Surface Functionalization of Gold Nanorods Using DNA Origami Clamps. AB - Precise control over surface functionalities of nanomaterials offers great opportunities for fabricating complex functional nanoarchitectures but still remains challenging. In this work, we successfully developed a novel strategy to modify a gold nanorod (AuNR) with specific surface recognition sites using a DNA origami clamp. AuNRs were encapsulated by the DNA origami through hybridization of single-stranded DNA on the AuNRs and complementary capture strands inside the clamp. Another set of capture strands on the outside of the clamp create the specific recognition sites on the AuNR surface. By means of this strategy, AuNRs were site-specifically modified with gold nanoparticles at the top, middle, and bottom of the surface, respectively, to construct a series of well-defined heterostructures with controlled "chemical valence". Our study greatly expands the utility of DNA origami as a tool for building complex nanoarchitectures and represents a new approach for precise tailoring of nanomaterial surfaces. PMID- 26824751 TI - Rh(III)-Catalyzed Synthesis of N-Unprotected Indoles from Imidamides and Diazo Ketoesters via C-H Activation and C-C/C-N Bond Cleavage. AB - The synthesis of N-unprotected indoles has been realized via Rh(III)-catalyzed C H activation/annulation of imidamides with alpha-diazo beta-ketoesters. The reaction occurs with the release of an amide coproduct, which originates from both the imidamide and the diazo as a result of C?N cleavage of the imidamide and C-C(acyl) cleavage of the diazo. A rhodacyclic intermediate has been isolated and a plausible mechanism has been proposed. PMID- 26824750 TI - Non-Native Plant Invasion along Elevation and Canopy Closure Gradients in a Middle Rocky Mountain Ecosystem. AB - Mountain environments are currently among the ecosystems least invaded by non native species; however, mountains are increasingly under threat of non-native plant invasion. The slow pace of exotic plant invasions in mountain ecosystems is likely due to a combination of low anthropogenic disturbances, low propagule supply, and extreme/steep environmental gradients. The importance of any one of these factors is debated and likely ecosystem dependent. We evaluated the importance of various correlates of plant invasions in the Wallowa Mountain Range of northeastern Oregon and explored whether non-native species distributions differed from native species along an elevation gradient. Vascular plant communities were sampled in summer 2012 along three mountain roads. Transects (n = 20) were evenly stratified by elevation (~70 m intervals) along each road. Vascular plant species abundances and environmental parameters were measured. We used indicator species analysis to identify habitat affinities for non-native species. Plots were ordinated in species space, joint plots and non-parametric multiplicative regression were used to relate species and community variation to environmental variables. Non-native species richness decreased continuously with increasing elevation. In contrast, native species richness displayed a unimodal distribution with maximum richness occurring at mid-elevations. Species composition was strongly related to elevation and canopy openness. Overlays of trait and environmental factors onto non-metric multidimensional ordinations identified the montane-subalpine community transition and over-story canopy closure exceeding 60% as potential barriers to non-native species establishment. Unlike native species, non-native species showed little evidence for high elevation or closed-canopy specialization. These data suggest that non-native plants currently found in the Wallowa Mountains are dependent on open canopies and disturbance for establishment in low and mid elevations. Current management objectives including restoration to more open canopies in dry Rocky Mountain forests, may increase immigration pressure of non-native plants from lower elevations into the montane and subalpine zones. PMID- 26824752 TI - Quasi-experimental evaluation of a home care model for patients with stroke in China. AB - PURPOSE: To evaluate the effectiveness of a modified home care model in China. METHODS: First-time stroke survivors were recruited from a comprehensive teaching hospital in China. Subjects in the intervention group (n = 168) received modified home care involving detailed pre-discharge preparation and post-discharge follow up lasting one month. The following outcomes were assessed at the end of follow up: length of hospital stay, satisfaction with acute hospitalisation, medication compliance, complications and stroke-related re-hospitalisation. The outcomes were compared for the intervention group and a historical control group (n = 173) who received routine care. RESULTS: Modified home care was associated with shorter acute hospitalisation (11.29 +/- 2.18 vs. 12.36 +/- 4.33 d, p = 0.03), higher compliance [161 (95.83%) vs. 92 (53.18%), p = 0.004] and ability to perform daily activities (38.25 +/- 10.22 vs. 32.08 +/- 10.32, p = 0.03), and a lower rate of re-hospitalisation [2 (1.19%) vs. 11 (6.36%), p = 0.02]. CONCLUSIONS: Home care may be associated with higher quality of life and reduced dependency among stroke patients in China. Implications for Rehabilitation Home care can be effective method at improving the physical and psychological well being of stroke survivors in China. The home care model in this study can improve health outcomes as well as reduce healthcare resources utilisation. Home care models for stroke survivors should be adapted to local healthcare policies and resources. PMID- 26824753 TI - RNA Whole-Mount In situ Hybridisation Proximity Ligation Assay (rISH-PLA), an Assay for Detecting RNA-Protein Complexes in Intact Cells. AB - Techniques for studying RNA-protein interactions have lagged behind those for DNA protein complexes as a consequence of the complexities associated with working with RNA. Here we present a method for the modification of the existing In Situ Hybridisation-Proximity Ligation Assay (ISH-PLA) protocol to adapt it to the study of RNA regulation (rISH-PLA). As proof of principle we used the well characterised interaction of the Xenopus laevis Staufen RNA binding protein with Vg1 mRNA, the complex of which co-localises to the vegetal pole of Xenopus oocytes. The applicability of both the Stau1 antibody and the Locked Nucleic Acid probe (LNA) recognising Vg1 mRNA were independently validated by whole-mount Immunohistochemistry and whole-mount in situ hybridisation assays respectively prior to combining them in the rISH-PLA assay. The rISH-PLA assay allows the identification of a given RNA-protein complex at subcellular and single cell resolution, thus avoiding the lack of spatial resolution and sensitivity associated with assaying heterogenous cell populations from which conventional RNA-protein interaction detection techniques suffer. This technique will be particularly usefully for studying the activity of RNA binding proteins (RBPs) in complex mixtures of cells, for example tissue sections or whole embryos. PMID- 26824754 TI - Factors Influencing Intraocular Pressure Changes after Laser In Situ Keratomileusis with Flaps Created by Femtosecond Laser or Mechanical Microkeratome. AB - The aim of this study is to describe factors that influence the measured intraocular pressure (IOP) change and to develop a predictive model after myopic laser in situ keratomileusis (LASIK) with a femtosecond (FS) laser or a microkeratome (MK). We retrospectively reviewed preoperative, intraoperative, and 12-month postoperative medical records in 2485 eyes of 1309 patients who underwent LASIK with an FS laser or an MK for myopia and myopic astigmatism. Data were extracted, such as preoperative age, sex, IOP, manifest spherical equivalent (MSE), central corneal keratometry (CCK), central corneal thickness (CCT), and intended flap thickness and postoperative IOP (postIOP) at 1, 6 and 12 months. Linear mixed model (LMM) and multivariate linear regression (MLR) method were used for data analysis. In both models, the preoperative CCT and ablation depth had significant effects on predicting IOP changes in the FS and MK groups. The intended flap thickness was a significant predictor only in the FS laser group (P < .0001 in both models). In the FS group, LMM and MLR could respectively explain 47.00% and 18.91% of the variation of postoperative IOP underestimation (R2 = 0.47 and R(2) = 0.1891). In the MK group, LMM and MLR could explain 37.79% and 19.13% of the variation of IOP underestimation (R(2) = 0.3779 and 0.1913 respectively). The best-fit model for prediction of IOP changes was the LMM in LASIK with an FS laser. PMID- 26824755 TI - Impact of Phanerochaete chrysosporium on the Functional Diversity of Bacterial Communities Associated with Decaying Wood. AB - Bacteria and fungi naturally coexist in various environments including forest ecosystems. While the role of saprotrophic basidiomycetes in wood decomposition is well established, the influence of these fungi on the functional diversity of the wood-associated bacterial communities has received much less attention. Based on a microcosm experiment, we tested the hypothesis that both the presence of the white-rot fungus Phanerochaete chrysosporium and the wood, as a growth substrate, impacted the functional diversity of these bacterial communities. Microcosms containing sterile sawdust were inoculated with a microbial inoculum extracted from a forest soil, in presence or in absence of P. chrysosporium and subsequently, three enrichment steps were performed. First, bacterial strains were isolated from different microcosms previously analyzed by 16S rRNA gene based pyrosequencing. Strains isolated from P. chrysosporium mycosphere showed less antagonism against this fungus compared to the strains isolated from the initial forest soil inoculum, suggesting a selection by the fungus of less inhibitory bacterial communities. Moreover, the presence of the fungus in wood resulted in a selection of cellulolytic and xylanolytic bacterial strains, highlighting the role of mycospheric bacteria in wood decomposition. Additionally, the proportion of siderophore-producing bacteria increased along the enrichment steps, suggesting an important role of bacteria in iron mobilization in decaying-wood. Finally, taxonomic identification of 311 bacterial isolates revealed, at the family level, strong similarities with the high throughput sequencing data as well as with other studies in terms of taxonomic composition of the wood-associated bacterial community, highlighting that the isolated strains are representative of the wood-associated bacterial communities. PMID- 26824756 TI - Late reproductive analysis in rat male offspring exposed to nicotine during pregnancy and lactation. AB - We previously observed that nicotine, administered to rats (Wistar) during pregnancy and lactation periods, provokes, in the progeny, late morphofunctional alterations in Leydig cell, body weight increase in adulthood (90 days post partum, dpp) as well as seminiferous epithelium injury. Aiming to investigate whether the spermatogenic damage previously observed in adult progenies from pregnant and lactating nicotine-exposed rat dams are maintained or whether it is worsened in older rats, we analyzed the morphological testicular alterations after up to two complete periods of spermatogenesis (53 days each), spermatic parameters, and sperm DNA fragmentation. Pregnant and lactating rats were nicotine-exposed (2 mg/kg/day) through an osmotic minipump implanted on the first day of pregnancy and replaced after birth. Absolute Control (no minipump) and Sham Control (minipump without nicotine) groups were established. The offspring were killed at 90, 143, and 196 dpp. Significant alterations in morphometric and stereological testicular parameters, such as concentration of sperm number, daily sperm production, and plasma and intratesticular levels of cholesterol and testosterone were not observed in nicotine-exposed rats. Testicular histopathological analysis showed small intraepithelial vacuolization and an accentuated germ cell desquamation in exposed rats. However, the offspring from nicotine-exposed dams exhibited higher frequency of morphologically abnormal spermatozoa and lower sperm motility in comparison with control groups. In addition, nicotine-exposed groups showed a significant reduction in sperm mitochondrial activity and an increased sperm DNA fragmentation (Comet assay). These results indicate a late reproductive damage in the male progeny caused by maternal nicotine exposure, related to the decrease in sperm quality. PMID- 26824757 TI - Case-control data analysis for randomly pooled biomarkers. AB - Pooled study designs, where individual biospecimens are combined prior to measurement via a laboratory assay, can reduce lab costs while maintaining statistical efficiency. Analysis of the resulting pooled measurements, however, often requires specialized techniques. Existing methods can effectively estimate the relation between a binary outcome and a continuous pooled exposure when pools are matched on disease status. When pools are of mixed disease status, however, the existing methods may not be applicable. By exploiting characteristics of the gamma distribution, we propose a flexible method for estimating odds ratios from pooled measurements of mixed and matched status. We use simulation studies to compare consistency and efficiency of risk effect estimates from our proposed methods to existing methods. We then demonstrate the efficacy of our method applied to an analysis of pregnancy outcomes and pooled cytokine concentrations. Our proposed approach contributes to the toolkit of available methods for analyzing odds ratios of a pooled exposure, without restricting pools to be matched on a specific outcome. PMID- 26824758 TI - A Statistical Approach to Provide Individualized Privacy for Surveys. AB - In this paper we propose an instrument for collecting sensitive data that allows for each participant to customize the amount of information that she is comfortable revealing. Current methods adopt a uniform approach where all subjects are afforded the same privacy guarantees; however, privacy is a highly subjective property with intermediate points between total disclosure and non disclosure: each respondent has a different criterion regarding the sensitivity of a particular topic. The method we propose empowers respondents in this respect while still allowing for the discovery of interesting findings through the application of well-known inferential procedures. PMID- 26824759 TI - Peer Review Quality and Transparency of the Peer-Review Process in Open Access and Subscription Journals. AB - BACKGROUND: Recent controversies highlighting substandard peer review in Open Access (OA) and traditional (subscription) journals have increased the need for authors, funders, publishers, and institutions to assure quality of peer-review in academic journals. I propose that transparency of the peer-review process may be seen as an indicator of the quality of peer-review, and develop and validate a tool enabling different stakeholders to assess transparency of the peer-review process. METHODS AND FINDINGS: Based on editorial guidelines and best practices, I developed a 14-item tool to rate transparency of the peer-review process on the basis of journals' websites. In Study 1, a random sample of 231 authors of papers in 92 subscription journals in different fields rated transparency of the journals that published their work. Authors' ratings of the transparency were positively associated with quality of the peer-review process but unrelated to journal's impact factors. In Study 2, 20 experts on OA publishing assessed the transparency of established (non-OA) journals, OA journals categorized as being published by potential predatory publishers, and journals from the Directory of Open Access Journals (DOAJ). Results show high reliability across items (alpha = .91) and sufficient reliability across raters. Ratings differentiated the three types of journals well. In Study 3, academic librarians rated a random sample of 140 DOAJ journals and another 54 journals that had received a hoax paper written by Bohannon to test peer-review quality. Journals with higher transparency ratings were less likely to accept the flawed paper and showed higher impact as measured by the h5 index from Google Scholar. CONCLUSIONS: The tool to assess transparency of the peer-review process at academic journals shows promising reliability and validity. The transparency of the peer-review process can be seen as an indicator of peer-review quality allowing the tool to be used to predict academic quality in new journals. PMID- 26824760 TI - Consequences of Secondary Calibrations on Divergence Time Estimates. AB - Secondary calibrations (calibrations based on the results of previous molecular dating studies) are commonly applied in divergence time analyses in groups that lack fossil data; however, the consequences of applying secondary calibrations in a relaxed-clock approach are not fully understood. I tested whether applying the posterior estimate from a primary study as a prior distribution in a secondary study results in consistent age and uncertainty estimates. I compared age estimates from simulations with 100 randomly replicated secondary trees. On average, the 95% credible intervals of node ages for secondary estimates were significantly younger and narrower than primary estimates. The primary and secondary age estimates were significantly different in 97% of the replicates after Bonferroni corrections. Greater error in magnitude was associated with deeper than shallower nodes, but the opposite was found when standardized by median node age, and a significant positive relationship was determined between the number of tips/age of secondary trees and the total amount of error. When two secondary calibrated nodes were analyzed, estimates remained significantly different, and although the minimum and median estimates were associated with less error, maximum age estimates and credible interval widths had greater error. The shape of the prior also influenced error, in which applying a normal, rather than uniform, prior distribution resulted in greater error. Secondary calibrations, in summary, lead to a false impression of precision and the distribution of age estimates shift away from those that would be inferred by the primary analysis. These results suggest that secondary calibrations should not be applied as the only source of calibration in divergence time analyses that test time-dependent hypotheses until the additional error associated with secondary calibrations is more properly modeled to take into account increased uncertainty in age estimates. PMID- 26824762 TI - Correction: Zonisamide Enhances Neurite Elongation of Primary Motor Neurons and Facilitates Peripheral Nerve Regeneration In Vitro and in a Mouse Model. PMID- 26824761 TI - ZMYND10--Mutation Analysis in Slavic Patients with Primary Ciliary Dyskinesia. AB - Primary ciliary dyskinesia (PCD) is a rare recessive disease with a prevalence of 1/10,000; its symptoms are caused by a kinetic dysfunction of motile cilia in the respiratory epithelium, flagella in spermatozoids, and primary cilia in the embryonic node. PCD is genetically heterogeneous: genotyping the already known PCD-related genes explains the genetic basis in 60-65% of the cases, depending on the population. While identification of new genes involved in PCD pathogenesis remains crucial, the search for new, population-specific mutations causative for PCD is equally important. The Slavs remain far less characterized in this respect compared to West European populations, which significantly limits diagnostic capability. The main goal of this study was to characterize the profile of causative genetic defects in one of the PCD-causing genes, ZMYND10, in the cohort of PCD patients of Slavic origin. The study was carried out using biological material from 172 unrelated PCD individuals of Polish origin, with no causative mutation found in nine major PCD genes. While none of the previously described mutations was found using the HRM-based screening, a novel frameshift mutation (c.367delC) in ZMYND10, unique for Slavic PCD population, was found in homozygous state in two unrelated PCD patients. Immunofluorescence analysis confirmed the absence of outer and inner dynein arms from the ciliary axoneme, consistent with the already published ZMYND10-mutated phenotype; cDNA analysis revealed the lack of ZMYND10 mRNA, indicating nonsense-mediated decay of the truncated transcript. PMID- 26824763 TI - Evaluating the Impact of Clinical Decision Tools in Pediatric Acute Gastroenteritis: A Population-based Cohort Study. AB - OBJECTIVE: Acute gastroenteritis (AGE) is a leading cause of pediatric emergency department (ED) visits. Despite evidence-based guidelines, variation in adherence exists. Clinical decision tools can enhance evidence-based care, but little is known about their use and effectiveness in pediatric AGE. This study sought to determine if the following tools-1) pathways/order sets, 2) medical directives for oral rehydration therapy (ORT) or ondansetron, and 3) printed discharge instructions-are associated with AGE admission and ED revisits. METHODS: This was a retrospective population-based cohort study of all children 3 months-18 years with an AGE ED visit in Ontario, Canada, from 2008 to 2010, using linked survey and health administrative databases. Logistic regression models associating clinical decision tools (CDTs) with hospitalizations and revisits controlling for hospital and patient characteristics were employed. RESULTS: Of the 57,921 patient visits during the study period, there were 2,401 hospitalizations (4.2%). A total of 55,520 patients were discharged from the ED, with 2,378 (4.3%) experiencing a 72-hour return visit. In adjusted models, none of the tools were significantly associated with admission. Medical directive for ORT was associated with lower return visit rates (adjusted odds ratio [aOR] = 0.86, 95% confidence interval [CI] = 0.79-0.94] and printed discharge instructions with higher return visits (aOR = 1.33, 95% CI = 1.08-1.65); pathways/order sets and medical directives for ondansetron had no association. CONCLUSIONS: Admissions in children with AGE are not associated with the presence of CDTs. While ORT medical directives are associated with lower ED revisits, printed discharge instructions have the opposite effect. The simple presence/absence of decision support tools does not guarantee improved clinical outcomes. PMID- 26824764 TI - BJ-1108, a 6-Amino-2,4,5-Trimethylpyridin-3-ol Analog, Inhibits Serotonin-Induced Angiogenesis and Tumor Growth through PI3K/NOX Pathway. AB - 5-Hydroxytryptamine (5-HT) induces proliferation of cancer cells and vascular cells. In addition to 5-HT production by several cancer cells including gastrointestinal and breast cancer, a significant level of 5-HT is released from activated platelets in the thrombotic environment of tumors, suggesting that inhibition of 5-HT signaling may constitute a new target for antiangiogenic anticancer drug discovery. In the current study we clearly demonstrate that 5-HT induced angiogenesis was mediated through the 5-HT1 receptor-linked Gbetagamma/Src/PI3K pathway, but not through the MAPK/ERK/p38 pathway. In addition, 5-HT induced production of NADPH oxidase (NOX)-derived reactive oxygen species (ROS). In an effort to develop new molecularly targeted anticancer agents against 5-HT action in tumor growth, we demonstrate that BJ-1108, a derivative of 6-amino-2,4,5-trimethylpyridin-3-ol, significantly inhibited 5-HT-induced angiogenesis. In addition, BJ-1108 induced a significant reduction in the size and weight of excised tumors in breast cancer cell-inoculated CAM assay, showing proportionate suppression of tumor growth along with inhibition of angiogenesis. In human umbilical vein endothelial cells (HUVECs), BJ-1108 significantly suppressed 5-HT-induced ROS generation and phosphorylation of PI3K/Akt but not of Src. Unlike NOX inhibitors, BJ-1108, which showed better antioxidant activity than vitamin C, barely suppressed superoxide anion induced by mevalonate or geranylgeranyl pyrophosphate which directly activates NOX without help from other signaling molecules in HUVECs, implying that the anti-angiogenic action of BJ 1108 was not mediated through direct action on NOX activation, or free radical scavenging activity. In conclusion, BJ-1108 inhibited 5-HT-induced angiogenesis through PI3K/NOX signaling but not through Src, ERK, or p38. PMID- 26824765 TI - Therapeutic Use of 3beta-[N-(N',N'-Dimethylaminoethane) Carbamoyl] Cholesterol Modified PLGA Nanospheres as Gene Delivery Vehicles for Spinal Cord Injury. AB - Gene delivery holds therapeutic promise for the treatment of neurological diseases and spinal cord injury. Although several studies have investigated the use of non-viral vectors, such as polyethylenimine (PEI), their clinical value is limited by their cytotoxicity. Recently, biodegradable poly (lactide-co glycolide) (PLGA) nanospheres have been explored as non-viral vectors. Here, we show that modification of PLGA nanospheres with 3beta-[N-(N',N' dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) enhances gene transfection efficiency. PLGA/DC-Chol nanospheres encapsulating DNA were prepared using a double emulsion-solvent evaporation method. PLGA/DC-Chol nanospheres were less cytotoxic than PEI both in vitro and in vivo. DC-Chol modification improved the uptake of nanospheres, thereby increasing their transfection efficiency in mouse neural stem cells in vitro and rat spinal cord in vivo. Also, transgene expression induced by PLGA nanospheres was higher and longer-lasting than that induced by PEI. In a rat model of spinal cord injury, PLGA/DC-Chol nanospheres loaded with vascular endothelial growth factor gene increased angiogenesis at the injury site, improved tissue regeneration, and resulted in better recovery of locomotor function. These results suggest that DC-Chol-modified PLGA nanospheres could serve as therapeutic gene delivery vehicles for spinal cord injury. PMID- 26824766 TI - Predator Diet and Trophic Position Modified with Altered Habitat Morphology. AB - Empirical patterns that emerge from an examination of food webs over gradients of environmental variation can help to predict the implications of anthropogenic disturbance on ecosystems. This "dynamic food web approach" is rarely applied at the coastal margin where aquatic and terrestrial systems are coupled and human development activities are often concentrated. We propose a simple model of ghost crab (Ocypode quadrata) feeding that predicts changing dominant prey (Emerita talpoida, Talorchestia sp., Donax variablis) along a gradient of beach morphology and test this model using a suite of 16 beaches along the Florida, USA coast. Assessment of beaches included quantification of morphological features (width, sediments, slope), macrophyte wrack, macro-invertebrate prey and active ghost crab burrows. Stable isotope analysis of carbon ((13)C/(12)C) and nitrogen ((15)N/(14)N) and the SIAR mixing model were used to determine dietary composition of ghost crabs at each beach. The variation in habitat conditions displayed with increasing beach width was accompanied by quantifiable shifts in ghost crab diet and trophic position. Patterns of ghost crab diet were consistent with differences recorded across the beach width gradient with respect to the availability of preferred micro-habitats of principal macro-invertebrate prey. Values obtained for trophic position also suggests that the generalist ghost crab assembles and augments its diet in fundamentally different ways as habitat morphology varies across a highly dynamic ecosystem. Our results offer support for a functional response in the trophic architecture of a common food web compartment (ghost crabs, macro-invertebrate prey) across well-known beach morphologies. More importantly, our "dynamic food web approach" serves as a basis for evaluating how globally wide-spread sandy beach ecosystems should respond to a variety of anthropogenic impacts including beach grooming, beach re nourishment, introduction of non-native or feral predators and human traffic on beaches. PMID- 26824767 TI - Nine sesquiterpenes from Solanum torvum. AB - Three new sesquiterpenes, namely 3beta,11-dihydroxy-4,14-oxideenantioeudesmane (1), 1beta,10beta,12,14-tetrahydroxy-allo-aromadendrane (2) and 1beta,10beta,13,14-tetrahydroxy-allo-aromadendrane (3), along with six known sesquiterpenes (4-9), were isolated from the roots of Solanum torvum. Compound 4 and 5 are epimers, their main difference lies in the C-11 configulation. Normally, epimers do not make a huge difference in C NMR spectra, but in this kind of structure of A, B, C rings, and C ring is sterically strained structure, stericall effects influence strongly the (13)C NMR chemical shifts, when C-11 configulation changed, it makes a huge difference in the three ring of structure, such as C-6, C-7, C-11. New compound 2 and 3 are epimers and similar to compound 4 and 5, their just increase a hydroxy in C-1 and have a same regular pattern in C NMR spectra, otherwise, compound 5 was firstly confirmed by single-crystal X ray diffraction. PMID- 26824768 TI - The Role of Hybridization in the Evolution and Emergence of New Fungal Plant Pathogens. AB - Hybridization in fungi has recently been recognized as a major force in the generation of new fungal plant pathogens. These include the grass pathogen Zymoseptoria pseudotritici and the powdery mildew pathogen Blumeria graminis triticale of triticale. Hybridization also plays an important role in the transfer of genetic material between species. This process is termed introgressive hybridization and involves extensive backcrossing between hybrid and the parental species. Introgressive hybridization has contributed substantially to the successful spread of plant pathogens such as Ophiostoma ulmi and O. novo-ulmi, the causal agents of Dutch elm disease, and other tree pathogens such as the rust pathogen Melampsora. Hybridization occurs more readily between species that have previously not coexisted, so-called allopatric species. Reproductive barriers between allopatric species are likely to be more permissive allowing interspecific mating to occur. The bringing together of allopatric species of plant pathogens by global agricultural trade consequently increases the potential for hybridization between pathogen species. In light of global environmental changes, agricultural development, and the facilitated long distance spread of fungal plant pathogens, hybridization should be considered an important mechanism whereby new pathogens may emerge. Recent studies have gained insight into the genetics and biology of fungal hybrids. Here I summarize current knowledge about hybrid speciation and introgressive hybridization. I propose that future studies will benefit greatly from the availability of large genome data sets and that genome data provide a powerful resource in combination with experimental approaches for analyses of hybrid species. PMID- 26824770 TI - Correction: Improving Facility Performance in Infectious Disease Care in Uganda: A Mixed Design Study with Pre/Post and Cluster Randomized Trial Components. PMID- 26824771 TI - Cervical Cancer Screening in Partly HPV Vaccinated Cohorts - A Cost-Effectiveness Analysis. AB - BACKGROUND: Vaccination against the oncogenic human papillomavirus (HPV) types 16 and 18 will reduce the prevalence of these types, thereby also reducing cervical cancer risk in unvaccinated women. This (measurable) herd effect will be limited at first, but is expected to increase over time. At a certain herd immunity level, tailoring screening to vaccination status may no longer be worth the additional effort. Moreover, uniform screening may be the only viable option. We therefore investigated at what level of herd immunity it is cost-effective to also reduce screening intensity in unvaccinated women. METHODS: We used the MISCAN-Cervix model to determine the optimal screening strategy for a pre vaccination population and for vaccinated women (~80% decreased risk), assuming a willingness-to-pay of ?50,000 per quality-adjusted life year gained. We considered HPV testing, cytology testing and co-testing and varied the start age of screening, the screening interval and the number of lifetime screens. We then calculated the incremental cost-effectiveness ratio (ICER) of screening unvaccinated women with the strategy optimized to the pre-vaccination population as compared to with the strategy optimized to vaccinated women, assuming different herd immunity levels. RESULTS: Primary HPV screening with cytology triage was the optimal strategy, with 8 lifetime screens for the pre-vaccination population and 3 for vaccinated women. The ICER of screening unvaccinated women 8 times instead of 3 was ?28,085 in the absence of herd immunity. At around 50% herd immunity, the ICER reached ?50,000. CONCLUSION: From a herd immunity level of 50% onwards, screening intensity based on the pre-vaccination risk level becomes cost-ineffective for unvaccinated women. Reducing the screening intensity of uniform screening may then be considered. PMID- 26824772 TI - Right Sided Colon Cancer as a Distinct Histopathological Subtype with Reduced Prognosis. AB - BACKGROUND/AIMS: Recent data suggest that tumors of the right and left colon should be distinguished as they differ in clinical and molecular characteristics. METHODS: A total of 1,319 patients who underwent surgical resection for colon cancer (CC) were investigated. Tumors between the ileocecal valve and the hepatic flexure were classified as right CC (RCC), tumors between the splenic flexure and the rectum as left CC (LCC). RESULTS: RCC revealed a higher cause-specific mortality risk (hazard ratio 1.36, 95% CI 1.10-1.68, p = 0.005) and lower 5-year cause-specific (RCC 64.9%, 95% CI 60.4-69.4, LCC 70.7%, 95% CI 67.2-74.2, p = 0.032) and disease-free (RCC 56.0%, 95% CI 51.5-60.5, LCC 59.9%, 95% CI 56.2 63.6, p = 0.025) survival rates. RCCs were more often microsatellite instable (RCC 37.2%, LCC 13.0%, p < 0.001) and more often showed KRAS (RCC 42.5%, LCC 18.9%, p = 0.001) and BRAF mutations (RCC 26.6%, LCC 3.2%, p < 0.001). CONCLUSION: RCC and LCC differ significantly regarding clinical, histopathological and molecular genetic features and can be considered as distinct entities. The reduced prognosis of RCC may be caused by higher rates of microsatellite instability, KRAS and BRAF mutations. PMID- 26824773 TI - Organ Specificity and Functional Relevance of the Arterial Structure: A Comparative Study in the Kidney and the Skeletal Muscle with Electron Microscopy. AB - The differences in circulation among various organs are well known, but the structural differences have only been poorly investigated. In the present study the wall structure of arteries was observed with electron microscopy in rat kidney and skeletal muscle. The wall thickness was almost equal in both organs at about 40 MUm in luminal diameter, while it was relatively thin in the larger arteries and thick in the smaller arteries in the kidney compared with that in the skeletal muscle. The smooth muscle cells were regularly arranged in parallel in circular or slightly spiral orientation in the kidney, whereas those in the skeletal muscle were irregularly arranged in heterogeneous orientations. Extracellular matrices were more abundant in the arterial media in the skeletal muscle than in the kidney. The inner elastic lamina was continuous in the kidney, and arranged in longitudinal bundles in the skeletal muscle. The adventitial collagen fibers were abundant and dense in the skeletal muscle, and were scattered in small bundles in the fluid-filled spaces in the kidney. While the arteries in the skeletal muscle are under severe mechanical stress during muscle contraction and dilate dramatically during exercise, those in the kidney regulate glomerular pressure almost constantly. PMID- 26824774 TI - Inhibitors of beta-catenin affect the immuno-phenotype and functions of dendritic cells in an inhibitor-specific manner. AB - Many tumors are characterized by mutation-induced constitutive activation of beta catenin which promotes tumor growth and survival. Consequently, the development of specific beta-catenin inhibitors for tumor therapy has come into the focus of drug development. beta-Catenin was also shown to contribute to the tolerance promoting function of unstimulated dendritic cells (DCs). In response to activation, DCs acquire potent T cell stimulatory capacity and induce profound tumor antigen-specific immune responses. Here we asked for effects of pre clinically established beta-catenin inhibitors (CCT-031374, iCRT-5, PNU-75654) on mouse bone marrow-derived (BM)DCs. All three inhibitors moderately increased surface expression of MHCII, CD80, and CD86 on unstimulated DCs, but had no enhancing effect on their capacity to stimulate the proliferation of ovalbumin (OVA) specific CD4(+) T cells. CCT-031374 interfered with upregulation of costimulators (CD40, CD86) and cytokines (IL-1beta, TNF-alpha, IL-6, IL-10, IL 12) by LPS-stimulated DCs. Accordingly, this DC population displayed an impaired CD4(+) T cell stimulatory activity. iCRT-5 and PNU-75654 had no detrimental effects on the immuno-phenotype of stimulated DCs. Hence, DCs treated with iCRT-5 in the course of stimulation exerted comparably strong T cell proliferation as did control DCs. In contrast, DCs stimulated in the presence of PNU-75654 induced less T cell proliferation than the control population despite enhanced uptake and processing of OVA. Our findings suggest that the differential effects of beta catenin inhibitors on stimulated DCs reflect off target effects. Concerning potential application of beta-catenin inhibitors for tumor therapy, iCRT-5 may be most beneficial, since it did not exert detrimental effects on stimulated DCs. PMID- 26824775 TI - Optimization of enzymatic production of anti-diabetic peptides from black bean (Phaseolus vulgaris L.) proteins, their characterization and biological potential. AB - The aim was to optimize the production of bioactive peptides from black bean (Phaseolus vulgaris L.) protein isolate and to determine their biological potential using biochemical and in silico approaches. Protein fractions were generated using eight commercially available proteases after 2, 3 and 4 h and 1:20, 1:30 and 1:50 enzyme/substrate (E/S) ratios. The best combination of conditions to generate anti-diabetic peptides was with alcalase for 2 h and E/S of 1:20; with inhibition values for dipeptidyl peptidase IV (DPP-IV, 96.7%), alpha-amylase (53.4%) and alpha-glucosidase (66.1%). Generated peptides were characterized using LC-ESI-MS/MS. Molecular docking analysis was performed to predict individual peptide biological potential using DockingServer(r). Peptides EGLELLLLLLAG, AKSPLF and FEELN inhibited DPP-IV more efficiently in silico through free energy interactions of -9.8, -9.6 and -9.5 kcal mol(-1), respectively, than the control sitagliptin (-8.67 kcal mol(-1)). The peptide TTGGKGGK (-8.97 kcal mol(-1)) had higher inhibitory potential on alpha glucosidase compared to the control acarbose (-8.79 kcal mol(-1)). Peptides AKSPLF (-10.2 kcal mol(-1)) and WEVM (-10.1 kcal mol(-1)) generated a lower free energy interaction with the catalytic site of alpha-amylase in comparison with acarbose (-9.71 kcal mol(-1)). Bean peptides inhibited the tested enzymes through hydrogen bonds, polar and hydrophobic interactions. The main bindings on the catalytic site were with ASP192, GLU192 and ARG 253 on DPP-IV; TYR151, HIS201 and ILE235 on alpha-amylase; and ASP34, THR83 and ASN32 on alpha-glucosidase. For the first time, a systematic evaluation and characterization of the anti-diabetic peptides from black bean protein isolate is presented with the potential for inhibiting important molecular markers related to diabetes. PMID- 26824776 TI - Metabolic Effects of the pksCT Gene on Monascus aurantiacus Li As3.4384 Using Gas Chromatography--Time-of-Flight Mass Spectrometry-Based Metabolomics. AB - Monascus spp. have been used for the production of natural pigments and bioactive compounds in China for several centuries. Monascus can also produce the mycotoxin citrinin, restricting its use. Disruption of the pksCT gene in Monascus aurantiacus Li AS3.4384 reduces citrinin production capacity of this strain (Monascus PHDS26) by over 98%. However, it is unclear how other metabolites of M. aurantiacus Li AS3.4384 (the wild-type strain) are affected by the pksCT gene. Here, we used metabolomic analyses to compare red yeast rice (RYR) metabolite profiles of the wild-type strain and Monascus PHDS26 at different stages of solid state fermentation. A total of 18 metabolites forming components within the glycolysis, acetyl-CoA, amino acid, and tricarboxylic acid (TCA) cycle metabolic processes were found to be altered between the wild-type strain and Monascus PHDS26 at different stages of solid-state fermentation. Thus, these findings provide important insights into the metabolic pathways affected by the pksCT gene in M. aurantiacus. PMID- 26824778 TI - Proton Transfer and Structure-Specific Fluorescence in Hydrogen Bond-Rich Protein Structures. AB - Protein structures which form fibrils have recently been shown to absorb light at energies in the near UV range and to exhibit a structure-specific fluorescence in the visible range even in the absence of aromatic amino acids. However, the molecular origin of this phenomenon has so far remained elusive. Here, we combine ab initio molecular dynamics simulations and fluorescence spectroscopy to demonstrate that these intrinsically fluorescent protein fibrils are permissive to proton transfer across hydrogen bonds which can lower electron excitation energies and thereby decrease the likelihood of energy dissipation associated with conventional hydrogen bonds. The importance of proton transfer on the intrinsic fluorescence observed in protein fibrils is signified by large reductions in the fluorescence intensity upon either fully protonating, or deprotonating, the fibrils at pH = 0 or 14, respectively. Thus, our results point to the existence of a structure-specific fluorophore that does not require the presence of aromatic residues or multiple bond conjugation that characterize conventional fluorescent systems. The phenomenon may have a wide range of implications in biological systems and in the design of self-assembled functional materials. PMID- 26824777 TI - Regional Ventilation and Aerosol Deposition with Helium-Oxygen in Bronchoconstricted Asthmatic Lungs. AB - BACKGROUND: Theoretical models suggest that He-O2 as carrier gas may lead to more homogeneous ventilation and aerosol deposition than air. However, these effects have not been clinically consistent and it is unclear why subjects may or may not respond to the therapy. Here we present 3D-imaging data of aerosol deposition and ventilation distributions from subjects with asthma inhaling He-O2 as carrier gas. The data are compared with those that we previously obtained from a similar group of subjects inhaling air. METHODS: Subjects with mild-to-moderate asthma were bronchoconstricted with methacholine and imaged with PET-CT while inhaling aerosol carried with He-O2. Mean-normalized-values of lobar specific ventilation sV* and deposition sD* were derived and the factors affecting the distribution of sD* were evaluated along with the effects of breathing frequency (f) and regional expansion (FVOL). RESULTS: Lobar distributions of sD* and sV* with He-O2 were not statistically different from those previously measured with air. However, with He O2 there was a larger number of lobes having sV* and sD* closer to unity and, in those subjects with uneven deposition distributions, the correlation of sD* with sV* was on average higher (p < 0.05) in He-O2 (0.84 +/- 0.8) compared with air (0.55 +/- 0.28). In contrast with air, where the frequency of breathing during nebulization was associated with the degree of sD*-sV* correlation, with He-O2 there was no association. Also, the modulation of f on the correlation between FVOL and sD*/sV* in air, was not observed in He-O2. CONCLUSION: There were no differences in the inter-lobar heterogeneity of sD* or sV* in this group of mild asthmatic subjects breathing He-O2 compared with patients previously breathing air. Future studies, using these personalized 3D data sets as input to CFD models, are needed to understand if, and for whom, breathing He-O2 during aerosol inhalation may be beneficial. PMID- 26824779 TI - Inhibitory effect of glutamic acid on the scale formation process using electrochemical methods. AB - The formation of calcium carbonate CaCO3 in water has some important implications in geoscience researches, ocean chemistry studies, CO2 emission issues and biology. In industry, the scaling phenomenon may cause technical problems, such as reduction in heat transfer efficiency in cooling systems and obstruction of pipes. This paper focuses on the study of the glutamic acid (GA) for reducing CaCO3 scale formation on metallic surfaces in the water of Bir Aissa region. The anti-scaling properties of glutamic acid (GA), used as a complexing agent of Ca(2+) ions, have been evaluated by the chronoamperometry and electrochemical impedance spectroscopy methods in conjunction with a microscopic examination. Chemical and electrochemical study of this water shows a high calcium concentration. The characterization using X-ray diffraction reveals that while the CaCO3 scale formed chemically is a mixture of calcite, aragonite and vaterite, the one deposited electrochemically is a pure calcite. The effect of temperature on the efficiency of the inhibitor was investigated. At 30 and 40 degrees C, a complete scaling inhibition was obtained at a GA concentration of 18 mg/L with 90.2% efficiency rate. However, the efficiency of GA decreased at 50 and 60 degrees C. PMID- 26824780 TI - Impact of Proteins on Aggregation Kinetics and Adsorption Ability of Hematite Nanoparticles in Aqueous Dispersions. AB - The initial aggregation kinetics of hematite nanoparticles (NPs) that were conjugated with two model globular proteins-cytochrome c from bovine heart (Cyt) and bovine serum albumin (BSA)-were investigated over a range of monovalent (NaCl) and divalent (CaCl2) electrolyte concentrations at pH 5.7 and 9. The aggregation behavior of Cyt-NP conjugates was similar to that of bare hematite NPs, but the additional electrosteric repulsion increased the critical coagulation concentration (CCC) values from 69 mM to 113 mM in NaCl at pH 5.7. An unsaturated layer of BSA, a protein larger than Cyt, on hematite NPs resulted in fast aggregation at low salt concentrations and pH 5.7, due to the strong attractive patch-charge interaction. However, the BSA-NP conjugates could be stabilized simply by elevating salt concentrations, owing to the screening of the attractive patch-charge force and the increasing contribution from steric force. This study showed that the aggregation state of protein-conjugated NPs is proved to be completely switchable via ionic strength, pH, protein size, and protein coverage. Macroscopic Cu(II) sorption experiments further established that reducing aggregation of hematite NPs via tailoring ionic strength and protein conjugation could promote the metal uptake by hematite NPs under harsh conditions. PMID- 26824782 TI - Enhancing Therapeutic Efficacy and Reducing Cell Dosage in Stem Cell Transplantation Therapy for Ischemic Limb Diseases by Modifying the Cell Injection Site. AB - In conventional stem cell transplantation therapies for ischemic limb diseases, stem cells are generally transplanted into the ischemic region (IR), and most of the transplanted cells undergo hypoxia-mediated cell death. Due to massive cell death, the therapeutic efficacy is reduced and a high dose of stem cells is necessitated for the therapies. In this study, we investigated whether the therapeutic efficacy can be improved and the cell dosage can be reduced in the therapy for limb ischemia simply by modifying the stem cell injection site to a site where cell engraftment is improved and blood vessel sprouting is efficiently stimulated. Human mesenchymal stem cells (hMSCs) cultured under hypoxic condition, which simulates cells transplanted to IR, underwent extensive cell death in vitro. Importantly, cell death was significantly attenuated when hMSCs adhered first under normoxic condition for 24 h and then were exposed to hypoxic condition, which simulates cells transplanted to the border zone (BZ) in the upper thigh and migrated to IR. hMSCs, at doses of 2 * 10(5) or 2 * 10(6) cells, were injected into the IR or BZ of 5-week-old female athymic mice after ischemic hindlimb induction. Compared with human mesenchymal stem cell (hMSC) transplantation to the IR of mouse ischemic limbs, transplantation to the BZ significantly enhanced cell engraftment and paracrine factor secretion, which effectively stimulated vessel sprouting, enhanced blood perfusion in IR, and enabled the cell dosage reduction. Therefore, modification of the stem cell transplantation site would improve the current stem cell therapies for ischemic limb diseases in terms of cell dosage reduction and therapeutic efficacy enhancement. PMID- 26824783 TI - Identification of an Interfering Ligand Aptamer for EphB2/3 Receptors. AB - The Eph receptors are transmembrane proteins that belong to the receptor tyrosine kinases superfamily. Elevated Eph/ephrin expression levels have been associated with angiogenesis and tumor vasculature in many types of human cancers, including breast, lung, and prostate cancers, melanoma, and leukemia. In glioblastoma (GBM), the dysregulated expression of Eph receptors and of corresponding ephrin ligands has been associated with higher tumor grade and poor prognosis making them effective targets for therapeutic drugs. In this study, we describe the GL43.T, an anti-Eph aptamer, able to bind at high-affinity EphB3 and EphB2. Moreover, the GL43.T aptamer inhibits the glioma cell vitality and interferes with ephrine-B1 inhibition of chemotactic serum-stimulated cell migration. GL43.T aptamer represents a promising therapeutic molecule for EphB3-dependent cancers. PMID- 26824781 TI - Extracellular vesicles in cardiovascular calcification: expanding current paradigms. AB - Vascular calcification is a major contributor to the progression of cardiovascular disease, one of the leading causes of death in industrialized countries. New evidence on the mechanisms of mineralization identified calcification-competent extracellular vesicles (EVs) derived from smooth muscle cells, valvular interstitial cells and macrophages as the mediators of calcification in diseased heart valves and atherosclerotic plaques. However, the regulation of EV release and the mechanisms of interaction between EVs and the extracellular matrix leading to the formation of destabilizing microcalcifications remain unclear. This review focuses on current limits in our understanding of EVs in cardiovascular disease and opens up new perspectives on calcific EV biogenesis, release and functions within and beyond vascular calcification. We propose that, unlike bone-derived matrix vesicles, a large population of EVs implicated in cardiovascular calcification are of exosomal origin. Moreover, the milieu-dependent loading of EVs with microRNA and calcification inhibitors fetuin-A and matrix Gla protein suggests a novel role for EVs in intercellular communication, adding a new mechanism to the pathogenesis of vascular mineralization. Similarly, the cell type-dependent enrichment of annexins 2, 5 or 6 in calcifying EVs posits one of several emerging factors implicated in the regulation of EV release and calcifying potential. This review aims to emphasize the role of EVs as essential mediators of calcification, a major determinant of cardiovascular mortality. Based on recent findings, we pinpoint potential targets for novel therapies to slow down the progression and promote the stability of atherosclerotic plaques. PMID- 26824784 TI - Hierarchically MnO2-Nanosheet Covered Submicrometer-FeCo2O4-Tube Forest as Binder Free Electrodes for High Energy Density All-Solid-State Supercapacitors. AB - The current problem of the still relatively low energy densities of supercapacitors can be effectively addressed by designing electrodes hierarchically on micro- and nanoscale. Herein, we report the synthesis of hierarchically porous, nanosheet covered submicrometer tube forests on Ni foam. Chemical deposition and thermal treatment result in homogeneous forests of 750 nm diameter FeCo2O4 tubes, which after hydrothermal reaction in KMnO4 are wrapped in MnO2-nanosheet-built porous covers. The covers' thickness can be adjusted from 200 to 800 nm by KMnO4 concentration. An optimal thickness (380 nm) with a MnO2 content of 42 wt % doubles the specific capacitance (3.30 F cm(-2) at 1.0 mA cm( 2)) of the bare FeCo2O4-tube forests. A symmetric solid-state supercapacitor made from these binder-free electrodes achieves 2.52 F cm(-2) at 2 mA cm(-2), much higher than reported for capacitors based on similar core-shell nanowire arrays. The large capacitance and high cell voltage of 1.7 V allow high energy and power densities (93.6 Wh kg(-1), 10.1 kW kg(-1)). The device also exhibits superior rate capability (71% capacitance at 20 mA cm(-2)) and remarkable cycling stability with 94% capacitance retention being stable after 1500 cycles. PMID- 26824785 TI - Gene expression profiling of selenophosphate synthetase 2 knockdown in Drosophila melanogaster. AB - Selenium (Se) is an important trace element for many organisms and is incorporated into selenoproteins as selenocysteine (Sec). In eukaryotes, selenophosphate synthetase SPS2 is essential for Sec biosynthesis. In recent years, genetic disruptions of both Sec biosynthesis genes and selenoprotein genes have been investigated in different animal models, which provide important clues for understanding the Se metabolism and function in these organisms. However, a systematic study on the knockdown of SPS2 has not been performed in vivo. Herein, we conducted microarray experiments to study the transcriptome of fruit flies with knockdown of SPS2 in larval and adult stages. Several hundred differentially expressed genes were identified in each stage. In spite that the expression levels of other Sec biosynthesis genes and selenoprotein genes were not significantly changed, it is possible that selenoprotein translation might be reduced without impacting the mRNA level. Functional enrichment and network-based analyses revealed that although different sets of differentially expressed genes were obtained in each stage, they were both significantly enriched in the carbohydrate metabolism and redox processes. Furthermore, protein-protein interaction (PPI)-based network clustering analysis implied that several hub genes detected in the top modules, such as Nimrod C1 and regucalcin, could be considered as key regulators that are responsible for the complex responses caused by SPS2 knockdown. Overall, our data provide new insights into the relationship between Se utilization and several fundamental cellular processes as well as diseases. PMID- 26824786 TI - Topical emollient for preventing infection in preterm infants. AB - BACKGROUND: Breakdown of the developmentally immature epidermal barrier may permit entry for micro-organisms leading to invasive infection in preterm infants. Topical emollients may improve skin integrity and barrier function and thereby prevent invasive infection, a major cause of mortality and morbidity in preterm infants. OBJECTIVES: To assess the effect of topical application of emollients (ointments, creams, or oils) on the incidence of invasive infection, other morbidity, and mortality in preterm infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), MEDLINE via PubMed (1966 to August 2015), EMBASE (1980 to August 2015), and CINAHL (1982 to August 2015). We also searched clinical trials databases, conference proceedings, previous reviews and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that assessed the effect of prophylactic application of topical emollient (ointments, creams, or oils) on the incidence of invasive infection, mortality, other morbidity, and growth and development in preterm infants. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and undertook data extraction independently. We analysed the treatment effects in the individual trials and reported the risk ratio and risk difference for dichotomous data and mean difference for continuous data, with respective 95% confidence intervals. We used a fixed-effect model in meta-analyses and explored the potential causes of heterogeneity in subgroup analyses. MAIN RESULTS: We identified 18 eligible primary publications (21 trial reports). A total of 3089 infants participated in the trials. The risk of bias varied with lack of clarity on methods to conceal allocation in half of the trials and lack of blinding of caregivers or investigators in all of the trials being the main potential sources of bias.Eight trials (2086 infants) examined the effect of topical ointments or creams. Most participants were very preterm infants cared for in health-care facilities in high-income countries. Meta-analyses did not show evidence of a difference in the incidence of invasive infection (typical risk ratio (RR) 1.13, 95% confidence interval (CI) 0.97 to 1.31; low quality evidence) or mortality (typical RR 0.87, 95% CI 0.75 to 1.03; low quality evidence).Eleven trials (1184 infants) assessed the effect of plant or vegetable oils. Nine of these trials were undertaken in low- or middle-income countries and all were based in health-care facilities rather than home or community settings. Meta-analyses did not show evidence of a difference in the incidence of invasive infection (typical RR 0.71, 95% CI 0.51 to 1.01; low quality evidence) or mortality (typical RR 0.94, 95% CI 0.81 to 1.08; moderate quality evidence). Infants massaged with vegetable oil had a higher rate of weight gain (about 2.55 g/kg/day; 95% CI 1.76 to 3.34), linear growth (about 1.22 mm/week; 95% CI 1.01 to 1.44), and head growth (about 0.45 mm/week; 95% CI 0.19 to 0.70). These meta-analyses contained substantial heterogeneity. AUTHORS' CONCLUSIONS: The available data do not provide evidence that the use of emollient therapy prevents invasive infection or death in preterm infants in high-, middle- or low-income settings. Some evidence of an effect of topical vegetable oils on neonatal growth exists but this should be interpreted with caution because lack of blinding may have introduced caregiver or assessment biases. Since these interventions are low cost, readily accessible, and generally acceptable, further randomised controlled trials, particularly in both community- and health care facility-based settings in low-income countries, may be justified. PMID- 26824787 TI - Irradiation with narrowband-ultraviolet B suppresses phorbol ester-induced up regulation of H1 receptor mRNA in HeLa cells. AB - Conclusion These findings suggest that low dose irradiation with 310 nm NB-UVB specifically suppressed the up-regulation of H1R gene expression without inducing apoptosis and that UVB of shorter or longer wavelength than 310 nm NB-UVB had no such effects. Objective To develop a narrowband-ultraviolet B(NB-UVB) phototherapy for allergic rhinitis, this study investigated the effects of irradiation with NB-UVB at wavelength of 310 nm on phorbol-12-myristate-13 acetate (PMA)-induced up-regulation of histamine H1 receptor (H1R) mRNA in HeLa cells. Methods The mRNA levels of H1R in HeLa cells were measured using real-time RT-PCR. Apoptosis were evaluated with DNA fragmentation assay. Results PMA induced a significant increase in H1R mRNA expression in HeLa cells. Irradiation with 305 nm UVB and 310 nm NB-UVB, but not with 315 nm UVB at doses of 200 and 300 mJ/cm(2) significantly suppressed PMA-induced up-regulation of H1R mRNA. At a dose of 200 mJ/cm(2), irradiation with 305 nm UVB, but not with 310 nm NB-UVB, induced apoptosis, although exposure of the cells to both 305 and 310 nm UVB induced apoptosis at a dose of 300 mJ/cm(2) after PMA treatment in HeLa cells. Conversely, irradiation with 315 nm UVB at doses of 200 and 300 mJ/cm(2) did not induce apoptosis. PMID- 26824788 TI - Postassembly Transformation of a Catalytically Active Composite Material, Pt@ZIF 8, via Solvent-Assisted Linker Exchange. AB - 2-Methylimidazolate linkers of Pt@ZIF-8 are exchanged with imidazolate using solvent-assisted linker exchange (SALE) to expand the apertures of the parent material and create Pt@SALEM-2. Characterization of the material before and after SALE was performed. Both materials are active as catalysts for the hydrogenation of 1-octene, whereas the hydrogenation of cis-cyclohexene occurred only with Pt@SALEM-2, consistent with larger apertures for the daughter material. The largest substrate, beta-pinene, proved to be unreactive with H2 when either material was employed as a candidate catalyst, supporting the contention that substrate molecules, for both composites, must traverse the metal-organic framework component in order to reach the catalytic nanoparticles. PMID- 26824789 TI - Amorphous Aggregation of Cytochrome c with Inherently Low Amyloidogenicity Is Characterized by the Metastability of Supersaturation and the Phase Diagram. AB - Despite extensive studies on the folding and function of cytochrome c, the mechanisms underlying its aggregation remain largely unknown. We herein examined the aggregation behavior of the physiologically relevant two types of cytochrome c, metal-bound cytochrome c, and its fragment with high amyloidogenicity as predicted in alcohol/water mixtures. Although the aggregation propensity of holo cytochrome c was low due to high solubility, markedly unfolded apo cytochrome c, lacking the heme prosthetic group, strongly promoted the propensity for amorphous aggregation with increases in hydrophobicity. Silver-bound apo cytochrome c increased the capacity of fibrillar aggregation (i.e., protofibrils or immature fibrils) due to subtle structural changes of apo cytochrome c by strong binding of silver. However, mature amyloid fibrils were not detected for any of the cytochrome c variants or its fragment, even with extensive ultrasonication, which is a powerful amyloid inducer. These results revealed the intrinsically low amyloidogenicity of cytochrome c, which is beneficial for its homeostasis and function by facilitating the folding and minimizing irreversible amyloid formation. We propose that intrinsically low amyloidogenicity of cytochrome c is attributed to the low metastability of supersaturation. The phase diagram constructed based on solubility and aggregate type is useful for a comprehensive understanding of protein aggregation. Furthermore, amorphous aggregation, which is also viewed as a generic property of proteins, and amyloid fibrillation can be distinguished from each other by the metastability of supersaturation. PMID- 26824790 TI - Practicing attachment in the real world: improving maternal insightfulness and dyadic emotional availability at an outpatient community mental health clinic. AB - The purpose of the study was to examine the efficacy of an attachment-based intervention program practiced at an outpatient clinic. Changes in parental insightfulness and dyadic emotional availability were assessed in 32 mother-child dyads from pre- to post-intervention. At both data collection points, mothers were interviewed with the Insightfulness Assessment and the mother-child dyad was observed in play sessions coded with the Emotional Availability Scales. Findings revealed a strong association between maternal insightfulness and dyadic emotional availability, both before and after treatment. In terms of intervention efficacy, positive gains were observed in both insightfulness and dyadic emotional availability from pre- to post-intervention. Mothers who changed their classifications from non-insightful to insightful following the intervention showed the greatest gains in emotional availability. These findings have important implications for the type of interventions and service delivery model that could work in real world clinical settings. PMID- 26824792 TI - Modelling carbon stocks and fluxes in the wood product sector: a comparative review. AB - In addition to forest ecosystems, wood products are carbon pools that can be strategically managed to mitigate climate change. Wood product models (WPMs) simulating the carbon balance of wood production, use and end of life can complement forest growth models to evaluate the mitigation potential of the forest sector as a whole. WPMs can be used to compare scenarios of product use and explore mitigation strategies. A considerable number of WPMs have been developed in the last three decades, but there is no review available analysing their functionality and performance. This study analyses and compares 41 WPMs. One surprising initial result was that we discovered the erroneous implementation of a few concepts and assumptions in some of the models. We further described and compared the models using six model characteristics (bucking allocation, industrial processes, carbon pools, product removal, recycling and substitution effects) and three model-use characteristics (system boundaries, model initialization and evaluation of results). Using a set of indicators based on the model characteristics, we classified models using a hierarchical clustering technique and differentiated them according to their increasing degrees of complexity and varying levels of user support. For purposes of simulating carbon stock in wood products, models with a simple structure may be sufficient, but to compare climate change mitigation options, complex models are needed. The number of models has increased substantially over the last ten years, introducing more diversity and accuracy. Calculation of substitution effects and recycling has also become more prominent. However, the lack of data is still an important constraint for a more realistic estimation of carbon stocks and fluxes. Therefore, if the sector wants to demonstrate the environmental quality of its products, it should make it a priority to provide reliable life cycle inventory data, particularly regarding aspects of time and location. PMID- 26824791 TI - Comparing offline decoding performance in physiologically defined neuronal classes. AB - OBJECTIVE: Recently, several studies have documented the presence of a bimodal distribution of spike waveform widths in primary motor cortex. Although narrow and wide spiking neurons, corresponding to the two modes of the distribution, exhibit different response properties, it remains unknown if these differences give rise to differential decoding performance between these two classes of cells. APPROACH: We used a Gaussian mixture model to classify neurons into narrow and wide physiological classes. Using similar-size, random samples of neurons from these two physiological classes, we trained offline decoding models to predict a variety of movement features. We compared offline decoding performance between these two physiologically defined populations of cells. MAIN RESULTS: We found that narrow spiking neural ensembles decode motor parameters better than wide spiking neural ensembles including kinematics, kinetics, and muscle activity. SIGNIFICANCE: These findings suggest that the utility of neural ensembles in brain machine interfaces may be predicted from their spike waveform widths. PMID- 26824794 TI - Why Write? PMID- 26824793 TI - Morphological Evolution of High-Voltage Spinel LiNi(0.5)Mn(1.5)O4 Cathode Materials for Lithium-Ion Batteries: The Critical Effects of Surface Orientations and Particle Size. AB - An evolution panorama of morphology and surface orientation of high-voltage spinel LiNi(0.5)Mn(1.5)O4 cathode materials synthesized by the combination of the microwave-assisted hydrothermal technique and a postcalcination process is presented. Nanoparticles, octahedral and truncated octahedral particles with different preferential growth of surface orientations are obtained. The structures of different materials are studied by X-ray diffraction (XRD), Raman spectroscopy, X-ray absorption near edge spectroscopy (XANES), and transmission electron microscopy (TEM). The influence of various morphologies (including surface orientations and particle size) on kinetic parameters, such as electronic conductivity and Li(+) diffusion coefficients, are investigated as well. Moreover, electrochemical measurements indicate that the morphological differences result in divergent rate capabilities and cycling performances. They reveal that appropriate surface-tailoring can satisfy simultaneously the compatibility of power capability and long cycle life. The morphology design for optimizing Li(+) transport and interfacial stability is very important for high voltage spinel material. Overall, the crystal chemistry, kinetics and electrochemical performance of the present study on various morphologies of LiNi(0.5)Mn(1.5)O4 spinel materials have implications for understanding the complex impacts of electrode interface and electrolyte and rational design of rechargeable electrode materials for lithium-ion batteries. The outstanding performance of our truncated octahedral LiNi(0.5)Mn(1.5)O4 materials makes them promising as cathode materials to develop long-life, high energy and high power lithium-ion batteries. PMID- 26824795 TI - Effects of Compression Stockings on Elevation of Leg Lymph Pumping Pressure and Improvement of Quality of Life in Healthy Female Volunteers: A Randomized Controlled Trial. AB - BACKGROUND: Lymph is pumped through the collecting lymphatic vessels by both intrinsic and extrinsic forces. The intrinsic pump relies on spontaneous lymphatic contraction, which generates the pumping lymph pressure (Plp). Among healthy people with daily leg edema, a considerable number of cases are accompanied with low leg Plp. Herein, a double-blinded controlled trial was conducted in healthy female volunteers with reduced leg Plp to compare the effectiveness of a 15-29 mmHg compression stocking (Stocking A) and a 8-16 mmHg stocking (Stocking B) on elevating Plp. METHOD AND RESULTS: Among 219 healthy female volunteers who underwent measurement of leg Plp, 80 participants (36.5%) had unilateral or bilateral legs with Plp < 20 mmHg (122 legs with Plp < 20 mmHg and 38 legs with Plp ? 20 mmHg). These 80 participants were assigned to wear either Stocking A (n = 40) or Stocking B (n = 40) for 16 weeks. Leg Plp was measured using indocyanine green fluorescence lymphography and an occlusion cuff technique while sitting. At 16 weeks, both Stockings A and B resulted in significantly elevated leg Plp, with the effect on elevating Plp being superior for Stocking A. Only Stocking A resulted in decreased prevalence of leg edema and improved Short Form-36 scores. CONCLUSION: Compression stockings may represent a therapeutic option to elevate leg Plp and ameliorate leg edema, thereby leading to improved quality of life in healthy females with low leg Plp. PMID- 26824796 TI - Wild Birds in Romania Are More Exposed to West Nile Virus Than to Newcastle Disease Virus. AB - The aim of this study was to evaluate the seroprevalence of West Nile virus (WNV) and Newcastle disease virus (NDV) in wild and domestic birds from Romania. During 2011-2014, 159 plasma samples from wild birds assigned to 11 orders, 27 families, and 61 species and from 21 domestic birds (Gallus gallus domesticus, Anas platyrhynchos domesticus) were collected. The sera were assayed by two commercial competitive enzyme-linked immunosorbent assay (cELISA) kits for antibodies against WNV and NDV. We found a high prevalence of WNV antibodies in both domestic (19.1%) and wild (32.1%) birds captured after the human epidemic in 2010. Moreover, the presence of anti-NDV antibodies among wild birds from Romania (5.4%) was confirmed serologically for the first time, as far as we are aware. Our findings provide evidence that wild birds, especially resident ones are involved in local West Nile and Newcastle disease enzootic and epizootic cycles. These may allow virus maintenance and spread and also enhance the chance of new outbreaks. PMID- 26824797 TI - Development of novel aminothiazole-comprising 5-LO inhibitors. AB - BACKGROUND: Leukotrienes are pivotal lipid mediators in various immune and inflammatory reactions. Herein, 5-LO is a validated target. 2-Aminothiazoles, as a privileged structure, implicate known 5-LO inhibitors like ST-1083 (IC50 [polymorphonuclear leukocytes (PMNL)] = 0.68 MUM), yet deep structure-activity relationships (SAR) have not been established. MATERIALS & METHODS: Compounds were synthesized via Hantzsch thiazole synthesis. Inhibitory activities were evaluated using intact PMNL and purified 5-LO together with cytotoxicity measurements in U937 cells. RESULTS: We introduced novel functionalities at 2-, 3 , 4- and 5-position of the 2-aminothiazole scaffold and conducted bioisosteric replacement to optimize the parent scaffold. SARs of the 2-aminothiazole scaffold were deduced and extended primarily for inhibition of the 5-LO enzyme. CONCLUSION: SAR studies provided at least two optimized leads (ST-1853, ST-1906) with high potency (IC50 [polymorphonuclear leukocytes] = 0.05 MUM), specificity and noncytotoxic behavior. PMID- 26824798 TI - Cell-Surface MMP-9 Protein Is a Novel Functional Marker to Identify and Separate Proangiogenic Cells from Early Endothelial Progenitor Cells Derived from CD133(+) Cells. AB - To develop cell therapies for ischemic diseases, endothelial progenitor cells (EPCs) have been expected to play a pivotal role in vascular regeneration. It is desirable to use a molecular marker that is related to the function of the cells. Here, a quantitative polymerase chain reaction array revealed that early EPCs derived from CD133(+) cells exhibited significant expression of MMP-9. Some populations of early EPCs expressed MMP-9 on the cell surface and others did not. We also attempted to separate the proangiogenic fraction from early EPCs derived from CD133(+) cells using a functional cell surface marker, and we then analyzed the MMP-9(+) and MMP-9(-) cell fractions. The MMP-9(+) cells not only revealed higher invasion ability but also produced a high amount of IL-8. Moreover, the stimulative effect of MMP-9(+) cells on angiogenesis in vitro and in vivo was prohibited by anti-IL-8 antibody. These data indicate that MMP-9 is one of the useful cell surface markers for the separation of angiogenic cells. Our treatment of early EPCs with hyaluronidase caused not only a downregulation of cell-surface MMP-9 but also a decrease in invasion ability, indicating that membrane-bound MMP 9, which is one of the useful markers for early EPCs, plays an important role in angiogenesis. Stem Cells 2016;34:1251-1262. PMID- 26824799 TI - Triphasic scaffolds for the regeneration of the bone-ligament interface. AB - A triphasic scaffold (TPS) for the regeneration of the bone-ligament interface was fabricated combining a 3D fiber deposited polycaprolactone structure and a polylactic co-glycolic acid electrospun. The scaffold presented a gradient of physical and mechanical properties which elicited different biological responses from human mesenchymal stem cells. Biological test were performed on the whole TPS and on scaffolds comprised of each single part of the TPS, considered as the controls. The TPS showed an increase of the metabolic activity with culturing time that seemed to be an average of the controls at each time point. The importance of differentiation media for bone and ligament regeneration was further investigated. Metabolic activity analysis on the different areas of the TPS showed a similar trend after 7 days in both differentiation media. Total alkaline phosphatase (ALP) activity analysis showed a statistically higher activity of the TPS in mineralization medium compared to the controls. A different glycosaminoglycans amount between the TPS and its controls was detected, displaying a similar trend with respect to ALP activity. Results clearly indicated that the integration of electrospinning and additive manufacturing represents a promising approach for the fabrication of scaffolds for the regeneration of tissue interfaces, such as the bone-to-ligament one, because it allows mimicking the structural environment combining different biomaterials at different scales. PMID- 26824800 TI - The rural scholar: anathema or archetype? PMID- 26824802 TI - President's message. Who provides emergency care in most of Canada? PMID- 26824804 TI - Location decisions of family physicians in Saskatchewan: What really matters? AB - INTRODUCTION: Residents of Saskatchewan, particularly those in rural communities, have less access to family physician services than people in other parts of the country. This is partly due to the difficulty of attracting and retaining physicians. The objective of this study was to understand the major factors that influence the location decisions of family physicians in Saskatchewan. METHODS: We employed a mixed-methods approach, including a questionnaire survey of family physicians and interviews with individuals from stakeholder health agencies. We used interpretive description to analyze interview responses. RESULTS: Neither family physicians nor interviewees from health agencies named compensation as the most influential factor in location decisions. More important factors were family influences, work-life balance and community influences. CONCLUSION: We recommend that recruitment of family physicians be regarded as a matching process, in which family physicians and communities are strategically matched. Compensating incentives should be targeted at communities that cannot meet the requirements of family physicians. PMID- 26824805 TI - Practice locations of longitudinal integrated clerkship graduates: a matched cohort study. AB - INTRODUCTION: Longitudinal integrated clerkships (LICs) have been introduced as an innovative model to impart medical education. In Canada, most LIC experiences are situated in rural communities. Studies have reported equivalence in graduates from rural LICs and traditional rotation-based clerkships (RBCs) in their performance in residency, as well as in national medical licensure examinations. We sought to determine the impact of rural LICs in terms of practice location of graduates. METHODS: A matched cohort was developed on the basis of student background and sex to compare practice location of rural LIC and RBC graduates. We used the chi(2) test to assess the association between type of clerkship stream and practice location. RESULTS: We found an association between participation in a rural LIC and rural practice location. CONCLUSION: Rural LIC programs play an important role in introducing students to rural medicine and may be an effective tool in responding to the shortage of rural practitioners. PMID- 26824806 TI - Closing rural maternity services: Is it worth the risk? PMID- 26824807 TI - The occasional intrauterine device insertion. PMID- 26824808 TI - Rural reflections: a year of practice. PMID- 26824809 TI - Point-of-care ultrasonography training for rural family medicine residents--its time has arrived. PMID- 26824810 TI - Prevalence and pathogenic potential of Escherichia coli isolates from raw milk and raw milk cheese in Egypt. AB - The objectives of this study were to investigate prevalence and pathogenic potential of Escherichia coli contaminating raw milk and its products in Egypt. Out of 187 dairy products including 72 raw milk samples, 55 Karish cheese and 60 Ras cheese, 222 E. coli isolates including 111, 89 and 22 were obtained from 55 raw milk samples (76.4%), 41 Karish cheese (74.5%), and 13 Ras cheese (21.7%), respectively. Isolated E. coli strains were examined for 24 representative virulence genes present in diarrheagenic E. coli (DEC) and extraintestinal pathogenic E. coli (ExPEC). Among DEC and ExPEC virulence factors, genes for enteropathogenic E. coli (eaeA, bfpA, EAF), enterohemorrhagic E. coli (stx1, stx2, eaeA), enterotoxigenic E. coli (elt, est), enteroinvasive E. coli (invE), enteroaggregative E. coli (Eagg, astA), diffusely adherent E. coli (daaD), ExPEC (cdt-I to cdt-V, cnf1, cnf2, hlyA) and putative adhesins (efa1, iha, ehaA, saa, and lpfAO113) were screened by colony hybridization assay. Out of 222 E. coli strains, 104 (46.8%) isolated from 69 (36.9%) samples carried one or more virulence genes. The most prevalent gene detected was lpfAO113 (40.5%), followed by ehaA (32.4%,), astA (3.15%,), iha (1.80%), hlyA (1.35%), stx1 (0.90%), stx2 (0.90%), eaeA (0.45%), cdt-III (0.45%) and cnf2 (0.45%). Two strains isolated from Karish cheese harbored 5 virulence genes (stx1, stx2, iha, ehaA, lpfAO113). Stx subtype was determined to be stx1 (not stx1c or stx1d) and stx2d. Indeed, expression of hemolysin A, CDT-III, CNF-II, Stx1 and Stx2d was confirmed by blood agar plate, cytotoxicity assay and Western blotting, respectively. Among the 222 E. coli strains, 54 (48.6%), 38 (42.6%) and 12 (54.7%) isolated from raw milk, Karish cheese and Ras cheese were potentially virulent, respectively. O genotyping indicated that most of the potentially virulent E. coli isolates did not belong to clinically important O serogroups except O75, O91 and O166, which have been associated with human diseases. Phylogenetic grouping revealed that 150 (67.6%), 67 (30.2%) and 5 (2.30%) strains were clustered into A, B1 and D groups, respectively, which are considered to be associated with intestinal infection, indicating that these E. coli strains might have a potential to cause gastroenteritis. To the best of our knowledge, this is the first comprehensive study regarding prevalence and pathogenic potential of E. coli in dairy products in Egypt. Raw milk, Karish cheese and Ras cheese in Egypt are highly contaminated with E. coli including potentially pathogenic strains, which may impose a public health threat. PMID- 26824811 TI - [Clinical pharmacology and pharmacotherapy: Problems and disputable issues]. AB - The paper discusses the current problems of internal medicine: the use of biologicals not only in rheumatology, but also in cardiology and pulmonology; current antiviral therapy for diseases of not only the liver, but also the heart (controversial issues); recent clinical data regarding LCZ (versus enalapril) and ivabradine (heart rate reduction). PMID- 26824812 TI - [Significance of papillary muscle function of the mitral valve and adjacent left ventricular segments in the progression of ischemic mitral regurgitation in patients with coronary heart disease after surgical treatment]. AB - AIM: To determine the significance of papillary muscle (PM) dysfunction of the mitral valve (MV) and adjacent left ventricular (LV) segments in the genesis of ischemic mitral regurgitation (MR) by myocardial tissue Doppler (MTD) in patients with coronary heart disease (CHD) after surgical treatment. SUBJECTS AND METHODS: One hundred and one CHD patients with moderate (grade I-II) MR were examined before surgical treatment. For analysis, the patients were divided into 4 groups: 1A) 40 patients without progressive, none or moderate MR after isolated aortocoronary bypass surgery (ACBS); 1B) 17 patients with progressive MR to its clinically relevant degree after isolated ACBS; 2A) 30 patients without progressive, none, or moderate MR after ACBS and surgical repair of postinfarction LV aneurysm; 2B) 14 patents with progressive MR to its clinically relevant degree after ACBS and surgical LV repair. The mean follow-up after surgery was 5.35+/-0.58 years. RESULTS: MTD analysis of the PM function of the MV and adjacent LV segments in the patients with CHD after surgical treatment indicated that those with progressive MR had 1) a decrease in the contractility of both PMs and adjacent LV segments; 2) a restrictive pattern of segmental diastolic dysfunction caused by the high myocardial rigidity of both PMs and adjacent LV segments; 3) an inverse correlation of the posterior PM systolic velocity S with the severity of MR, which is suggestive of the clinically important contribution of posterior PM contractility to the development of MR. There were correlations indicating that the high LV and PM rigidities leading to the restrictive pattern of myocardial diastolic impairments are involved in the development of MR in the patients with CHD. CONCLUSION: The results confirm that PM and adjacent LV segment dysfunctions are of significance in the mechanisms of progressive ischemic MR in the patients with CHD after surgical treatment. PMID- 26824813 TI - [The use of cardiointervalography for diagnostic screening and evaluation of the efficiency of correction of magnesium deficiency and comorbid conditions]. AB - AIM: To detect chronic diseases comorbid to magnesium (Mg) deficiency (ICD-10 E61.2) by the data of heart rate variability (HRV). SUBJECTS AND METHODS: The investigation enrolled 398 student patients from a university preventorium (52% youngsters; mean age, 18+/-9 years; height, 157+/-28 cm; weight, 54+/-20 kg). The database for each patient included anthropometric, dynamometric, electrooculometric, HRV and blood pressure monitoring data, plasma levels of vitamins, and collected scores of all stress items of the IDIX scale, MFI-20, asthenia rating scale, HAM test, a questionnaire for deficiency of Mg, vitamins, etc., i.e. a total of 521 parameters. A data sample for 398 patents was randomized into a learning subsample (n = 198) that was used to calculate the discussed sets of logical rules and an independent control sample (n = 200) that was employed to test the obtained sets of logical rules in order to determine their sensitivity and specificity. RESULTS: Based on the analysis of the collected database, the investigators established the pattern of diseases comorbid to Mg deficiency in the examined sample, elaborated diagnostic rules for a number of abnormalities, and checked the obtained sets of rules on the control subsample. The presence of more than half the diagnoses given below may be recognized on the basis of HRV and dynamometric, clinical, and laboratory findings and history data with a sensitivity of 70-95% and a specificity of 75 95%. It is shown that HRV data allow detection of a number of chronic diseases comorbid to Mg deficiency (ICD-10 E61.2) with a high degree of accuracy (on average of 80%) and selectivity (about 80%). CONCLUSION: The diagnostic method based on HRV measured by cardiointervalography has been developed, which, among other processes, permits the noninvasive evaluation of electrolyte balance and the identification of Mg, K, Na, and Ca deficiencies. The advantage of this method is that it can assess the body's overall functional possibilities in health, as well as early abnormalities that may gradually progress to serious diseases if no necessary preventive measures are implemented. The practical value of the developed method is demonstrated, by using Magnerot in vegetative dystonia concurrent with hypomagnesium. PMID- 26824814 TI - [Preventive cytoprotection in social diseases]. AB - Among many cytoprotective drugs, only a few of them that have a targeted metabolic effect include agents that partially inhibit oxidation of free fatty acids, the so-called p-FOX inhibitors (partial fatty acid oxidation inhibitors). AIM: To develop a procedure for the preventive use of meldonium dihydrate in day hospital patients with comorbidity. SUBJECTS AND METHODS: The investigation enrolled 189 patients (116 men and 73 women; mean age, 55.9+/-4.4 years) who were followed up for initial manifestations of cardiovascular and/or another somatic disease and were at high risk for unfavorable cardio- and cerebrovascular events, as well as complications of emergency alcohol-related conditions. The investigation of the efficacy and safety of meldonium dihydrate was planned as an open-label clinical trial in three parallel groups different in the directivity patterns of potential complications ("Cardio", "Cerebro", "Alco"). The drug's dosage averaged 500 to 1000 mg/day. RESULTS: The day-hospital use of meldonium dihydrate demonstrated high safety profile and a positive role in the prevention of cardio- and cerebrovascular catastrophes and complications of emergency alcohol-related conditions and chronic alcoholic visceropathy, leading to delayed dyslipidemia progression, diminished insulin resistance, improved blood rheological properties, and suppressed chronic systemic inflammation and also proving its role in the prevention of renal vascular injury and toxic (ethanol) encephalopathy. Meldonium therapy showed positive effects in delaying the progression of dyslipidemia, diminishing insulin resistance, improving blood rheological properties, and suppressing chronic systemic inflammation and also proved its role in preventing renal vascular injury and toxic (ethanol) encephalopathy, which confirmed the versatility of the cytoprotective effect of meldonium. CONCLUSION: The drug has proved to be effective and safe in hemodynamic, electrolytic, hepatic, and other parameters, which makes it expedient to include meldonium in the day-hospital formulary of drugs for a preventive parenteral cycle according to the developed regimen (a 10-day cycle at least 1-2 times a year) for patients at high risk for social diseases and their complications. PMID- 26824815 TI - [Chronic obstructive pulmonary disease concurrent with hypertension: Evaluation of the therapeutic effect of prolonged-release indapamide]. AB - AIM: To provide a rationale for the clinical efficacy and safety of prolonged release indapamide used in the combination therapy of patients with chronic obstructive pulmonary disease concurrent (COPD) concurrent with hypertension. SUBJECTS AND METHODS: Sixty-five patients (50 men and 15 women) with Stages I-IV COPD and grades 1-3 elevated blood pressure (BP) in whom prior antihypertensive therapy had proved insufficiently effective were examined. RESULTS: Prolonged release indapamide demonstrated a high efficacy in achieving and maintaining goal BP, in normalizing its daily profile, and in reducing increased variability and the rate of morning rise in BP, without negatively affecting the clinical manifestations of COPD, pulmonary ventilatory function, and serum potassium levels. The drug was shown to have additional pleiotropic effects in lowering the activity of inflammatory markers (high-sensitivity C-reactive protein, intercellular adhesion molecules-1) and the level of endothelial dysfunction markers (endothelin-1, sP-selectin). Another commonly clinically used diuretic hydrochlorothiazide was chosen as a compared drug. CONCLUSION: The high antihypertensive efficacy and additional pleiotropic properties of prolonged release indapamide that exerts no negative effect on the clinical manifestations of COPD, bronchial patency, and serum potassium levels demonstrate that it is expedient to incorporate prolonged-release indapamide into the combination therapy of patients with COPD concurrent with hypertension. PMID- 26824816 TI - [Genetic determinants of antibiotic resistance in oropharyngeal streptococci in patients with chronic obstructive pulmonary disease and in those with asthma]. AB - AIM: To identify oropharyngeal Streptococcus species and to analyze the genetic determinants of antibiotic resistance in patients with asthma and in those with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS: An experimental diagnostic Streptopol+ (Lytech Co. LTD) panel based on a multiplex real-time PCR was applied to investigate the representation of antimicrobial resistance genes (mef and ermB) and the species composition of streptococci isolated from oropharyngeal swab samples from 89 patients with stable COPD and from 51 patients with asthma. RESULTS: In the stable disease period, the oropharyngeal swabs were found to contain Streptococcus pneumoniae in 7.8% of the patients with asthma and in 6.74% of those with COPD; the common feature of these groups was a tendency towards a severe disease course and recurrent exacerbations requiring antibiotics. S. pyogenus was detected in 42.9% of the oropharyngeal swabs from COPD and asthma patients without exacerbations. The oropharyngeal swabs showed the mef gene in 100% of the patients with asthma and in 100% of those with COPD; the ermB gene was encountered in 91% of the patients with COPD and in 82.4% of those with asthma. The COPD patients displayed a direct correlation between the representation of the ermB gene and sputum production and smoking index. The mef and ermB genes were directly correlated with the frequency of exacerbations in patients with COPD. CONCLUSION: The identified streptococci are a reservoir of antimicrobial resistance genetic determinants - the mef and ermB genes encoding the mechanisms of streptococcal macrolide resistance. The representation of the above genes directly correlates with the frequency of exacerbations and the number of antimicrobial drug uses. PMID- 26824817 TI - [Use of a regional registry of chronic hepatitis patients to optimize antiviral therapy]. AB - AIM: To determine the general characteristics of patients with chronic viral hepatitis C (CVHC) from the data of a registry of patients with viral hepatitis (VH) in the Stavropol Territory and to estimate possible predictors for the inefficiency of antiviral therapy (AVT) for treatment optimization. SUBJECTS AND METHODS: The results of examining and treating patients with CVHC were retrospectively analyzed from the data of the registry of HV patients in the Stavropol Territory in 2008-2013. RESULTS: The chronic hepatitis registry includes 1811 patients with CVHC; out of them there are 64% who have its virus genotype 1. According to the registry, there is cirrhosis in 244 (13.5%) patients, fibrosis (METAVIR F2-F3 in 724 (39.97%), and fibrosis (METAVIR F0-F1) in the remaining 843. Carbohydrate and fat metabolic disturbances (obesity, insulin resistance (IR), and diabetes mellitus (DM)) have been found in 615 (34%) patients; every three patients have gastrointestinal diseases and comorbidity is absent in 24% of the patients. The results of AVT were analyzed in 493 patients with CHC virus genotype 1. The analysis showed the most important predictors for the inefficiency of AVT; these included HOMA-IR >2, the presence of IR (HOMA-IR >2.77), and type 2 DM, as well as patient age over 45 years, male sex, a viral load of >=6 log10 IU/ml, and liver fibrosis (METAVIR >=F3). CONCLUSION: The analysis of VH morbidity in the Stavropol Territory, the making of a registry of patients with chronic VH, its columns of IR, body mass index, virologic response changes during therapy could clarify the actual need in AVT and improve activities in the prophylactic medical examination and treatment optimization in this patient group in the areas of this region. PMID- 26824818 TI - [Efficacy of the infusion hepatotropic drug remaxol in the pathogenetic therapy for cirrhotic stage chronic viral hepatitides]. AB - AIM: To investigate the impact of therapy with the infusion hepatoprotector remaxol on liver function in cirrhosis in the outcome of chronic viral hepatitides (CVH): HCV, HBV, HCV+HBV, and HBV+HDV. SUBJECTS AND METHODS: Sixty five patients aged 26 to 76 years, who had been diagnosed as having liver cirrhosis (LC) in the outcome of CVH: HCV, HBV, HCV+HBV, and HBV+HDV were examined. During infusion therapy, every day 32 cirrhotic patients in the outcome of CVH B or C received intravenous remaxol 400 ml in a jetwise manner once daily for 11 days. A comparison group comprised 33 patients with the similar condition who had intravenous ademetionine 400 mg in a jetwise fashion during infusion therapy with crystalloids (400 ml of isotonic sodium chloride solution, Ringer's solution) for 11 days. RESULTS: After an infusion therapy cycle, the study group patients were recorded to have more significantly reduced cytolytic and cholestatic parameters. The pronounced hepatotropic effect of the drug was confirmed by the rate of a decline in the average concentrations of alanine aminotransferase, aspartate aminotransferase, and total bilirubin. In the study group patients, the relative values of a decrease in the levels of these biochemical parameters were 29, 29, and 40% versus 15, 20, and 9% in the control patients. CONCLUSION: Infusion therapy with remaxol in the combination treatment of the patients with viral LC not only improves liver function (reduces the degree of cytolysis, cholestasis), but also exerts a cytoprotective effect on peripheral blood cells (leukocytes, lymphocytes, platelets). PMID- 26824819 TI - [Use of biological therapy in patients with rheumatoid arthritis in the Republic of Kazakhstan]. AB - AIM: To evaluate the clinical efficacy and safety of infliximab (IFM) in patients with rheumatoid arthritis (RA). SUBJECTS AND METHODS: Twelve inpatients (10 women and 2 men) aged 23 to 65 years with a valid diagnosis of RA, the duration of which was 3 years or more, were retrospectively analyzed. DAS28 for RA corresponded to grades II and III in 4 (33.3%) and 8 (66.7%) patients, respectively. Long before the investigation, all the patients used methotrexate in a weekly dose of 15 mg and nonsteroidal anti-inflammatory drugs; 6 patients received methipred in a daily dose of 4-8 mg. IFM was administered intravenously dropwise on the basis of 3 mg/kg weight in 250 ml of isotonic sodium hydrochloride solution during 2 hours at 0, 2, and 6 weeks after therapy initiation and then every 8 weeks. RESULTS: During combination therapy after the first IFM infusion, all the 12 patients were noted to have a positive clinical effect as a significant reduction in the number of tender joints and swollen joints, morning stiffness, erythrocyte sedimentation rate, C-reactive protein, regression of the clinical manifestations of the disease, and its laboratory activity. The therapy was tolerated well by all the patients. According to the EULAR criteria, a good therapeutic effect was observed in 10 (83%) patients and clinical remission was achieved in 2 (17%) patients. According to the ACR criteria, 50 and 70% improvement was seen in 1 (8%) and 9 (75%) patients, respectively. Two (17%) patients achieved remission. CONCLUSION: Combination therapy with IFM and MT for RA is highly effective, suppresses disease inflammatory activity and joint destruction; furthermore, there may be remission induction. PMID- 26824820 TI - [Diagnosis and treatment in patients with B-cell lymphoma unclassified that is intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma]. AB - AIM: To characterize a group of patients with B-cell lymphoma (BCLU) unclassified that is intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma, to identify poor prognostic factors, and to evaluate therapeutic efficiency in patients with BCLU. SUBJECTS AND METHODS: Twenty-five patients with BCLU were examined. Double-hit lymphoma (DHL) was diagnosed in 8 (32%) patients. According to the Ann-Arbor classification of lymphoma, its stages II, III, and IV were diagnosed in 3 (12%), 2 (8%), and 20 (80%) patients, respectively. MYC rearrangement was observed in 11 (48%) out of 23 patients: single-hit lymphoma in 3 patients and DHL in 8 (BCL2+/MYC+ in 6 cases and BCL6+/MYC+ in 2). The expression of s-MYC (cut off >=40%) was revealed in 17 (74%) out of 23 patients; that of BCL2 (cut off >=50%) was detected in 14 (58%) out of 24 patients; coexpression of both proteins was seen in 12 (52%) out of 23 patients. The DHL group showed a correlation between the rearrangement of the BCL2+/MYC+ genes and the expression of MYC and BCL2 proteins in 5 out of 6 patients. Taking into account the heterogeneity of the entire patient group, DHL and non-DHL subgroups were considered separately. Both subgroups were comparable by clinical characteristics. BCLU patients younger than 60 years of age received treatment according to the LB-M-04 +/- rituximab; those aged 60 or older had CHOP-like regimens +/- rituximab. Autologous stem cell transplantation (auto-SCT) was performed in 5 patients belonging to a high-risk group. RESULTS: The 3-year overall survival (OS) was 62% and the 3-year event-free survival (EFS) was 51%. The 3-year OS was lower for the DHL group than that for the non-DHL group (43 and 75%, respectively). CONCLUSION: In the DHL group, both OS and EFS are significantly lower (the risk of poor outcome, including death, is higher) than those in the non-DHL group. It is conceivable that intensified chemotherapy with auto-SCT increases treatment results in patients with BCLU; however, a larger number of observations are needed to obtain valid data. PMID- 26824821 TI - [Investigation of the association between the HindIII polymorphism of the LPL gene and the Taq1b polymorphism of the CETP gene with the risk of atherothrombotic stroke in the dwellers of Central Russia]. AB - AIM: To investigate the association between LPL HindIII (rs320) and CETP Taq1b (rs708272) polymorphisms with the risk of atherothrombotic stroke (ATS) in the population of Central Russia. MATERIAL AND METHODS: A total of 832 DNA samples obtained from 417 patients with ATS and from 415 healthy individuals of the corresponding gender and age were investigated. The polymorphisms were genotyped by a real-time PCR assay using TaqMan probes. RESULTS: The carriage of heterozygous LPL +495TG genotype was found to be associated with the lower risk of ATS (odds ratio (OR)=0.71; 95% CI: 0.53-0.94; p=0.02). A gender-stratified analysis showed that in the men the variant LPL +495TG genotype was associated with the increased risk of ATS (OR=2.06; 95% CI: 1.03-4.14; r=0.04) while the heterozygous +495GG genotype had a protective effect against the risk of stroke (OR=0.66; 95% CI: 0.45-0.97; r=0.04). Variance analysis established that this polymorphism was found to be associated with the increased prothrombin index in the men with ATS (p=0.01). CONCLUSION: This study was the first to reveal the association of the LPL HindIII (rs320) polymorphism with the increased prothrombin index and the risk of ATS in the Russian male population. PMID- 26824822 TI - [IgG4-related salivary gland lesions]. AB - AIM: To provide the demographic, clinical, laboratory, radiological, morphological, and immunomorphological characteristics of IgG4-related sialoadenitis (IgG4-S), which allow the differential diagnosis with neuroendocrine, granulomatous, blood cancer lesions of the salivary gland (SG). SUBJECTS AND METHODS: In the period 2004 to 2014, IgG4-S was diagnosed in 32 (11%) out of 289 patients with significantly enlarged parotid and submandibular glands (PG and SMG). Only 4 (9%) patients had isolated IgG4-related disease (IgG4 D) whereas involvement of a few organs ran as an IgG4-SD systemic disease in 29 (91%) patients. RESULTS: There was a slight preponderance of women with a median onset age of 42 years. Enlargement of the SMG (52.7%), lesions of the nasal cavity and paranasal sinuses (37.2%), and enlargement of the lacrimal gland and orbital pseudotumors (31%) are the most common clinical manifestations at disease onset. A follow-up study indicated that along with involvements of SMG (97%), PG (72%), eye sockets (72%), nasal cavity and paranasal sinuses (56%), one third of the patients were found to have generalized lymphadenopathy, to frequently develop pulmonary, hepatic, pancreatic, renal injuries; and the disease ran within IgG4-SD. The laboratory manifestations were characterized by moderate eosinophilia and elevated blood IgE levels in one-third of the patients and by moderately higher erythrocyte sedimentation rate and hypergammaglobulinemia in 50%. The increased blood level of IgG (84%) and its subclass IgG4 (86.4%) is an indication for further verification of IgG4-D in patients with involvement of the major SG. Immunohistochemical examination, by measuring the concentration of IgG4 secreting plasma cells (PCs), and determination of B-cell clonality in biopsy specimens should be done to verify a diagnosis with IgG4-D. CONCLUSION: The determination of blood IgG4 (>2 g/l) in patients with considerably enlarged major SG may suggest the presence of IgG4-S. Minimally invasively incised PG and SMG biopsies with their subsequent morphological and immunomorphological examinations should be performed to make an accurate diagnosis. More than 40% of IgG4 secreting PCs detected in SG tissue is evidence to diagnose IgG4-D. PMID- 26824823 TI - Letter to the editor concerning the article "Performance of gymnastics skill benefits from an external focus of attention" by Abdollahipour, Wulf, Psotta & Nieto (2015). AB - Abdollahipour, Wulf, Psotta, and Nieto (2015) recently published data in the Journal of Sports Sciences to show that an external focus of attention promotes superior performance effects (gymnastics jump height and judged movement form score) when compared to internal or control foci during skill execution without an implement involved. While we do not contest the veracity of findings reported, nor others that have been used to support beneficial effects of an external focus of attention, in this Letter to the Editor we comment on considerable methodological limitations associated with this and previous studies that, we suggest, have resulted in serious theoretical oversights regarding the control of movement and, most crucially from our practitioner perspective, suboptimal recommendations for applied coaching practice. Specifically, we discuss the lack of consideration towards translational research in this area, the problematic nature of attentional focus cues employed, interpretation of findings in relation to other applied recommendations and coherence with mechanistic underpinning and, finally, the representative nature of task involved. In summary, while (laboratory) research evidence may appear to be conclusive, we suggest that the focus of attention effects are in need of more ecologically valid and rigorous testing as well as consideration of current coaching practices if it is to optimally serve the applied sporting domain that it purportedly aims to. PMID- 26824824 TI - Pattern of symptoms and symptomatic treatment in adults and the aged population: a retrospective analysis of advanced cancer patients followed at home. AB - Context Data regarding symptom burden and symptomatic drugs in palliative population in different classes of age are lacking. Objective The aim of this retrospective study was to assess the symptom burden, and the profile of symptomatic drugs in the last four weeks of life in adults and older cancer patients followed at home. Methods Charts of 412 patients were retrospectively analyzed by using a backward analysis. Patients were divided into three groups: adults (<65 years, A), old (65-74 years, O1), very old (75-84 years, O2), and the oldest (>=85 years, O3). Results At -4W Karnofsky status was significantly lower for older people (p = 0.03). No significant effect of age on the vector of symptoms was found (p = 0.07). A significant decrease in intensity of pain and nausea, and an increase in intensity of all other symptoms was found through the four weeks of the study (p = 0.00). No differences of drug pattern among the age categories were found. The use of symptomatic drugs decreased over time, except for opioids. Age statistically affected NSAID use, neuroleptic use, and antiemetics over time. Conclusion The burden of symptoms worsened in the last four weeks of life, except for pain and nausea, but did not differ among the age subgroups. The use of NSAIDs, neuroleptics, and antiemetics changed, while the frequency of opioid use was unchanged until death. PMID- 26824825 TI - Cerium Oxide Nanoparticle Modified Scaffold Interface Enhances Vascularization of Bone Grafts by Activating Calcium Channel of Mesenchymal Stem Cells. AB - Insufficient blood perfusion is one of the critical problems that hamper the clinical application of tissue engineering bone (TEB). Current methods for improving blood vessel distribution in TEB mainly rely on delivering exogenous angiogenic factors to promote the proliferation, migration, differentiation, and vessel formation of endothelial cells (ECs) and/or endothelial progenitor cells (EPCs). However, obstacles including limited activity preservation, difficulty in controlled release, and high cost obstructed the practical application of this strategy. In this study, TEB scaffold were modified with cerium oxide nanoparticles (CNPs) and the effects of CNPs existed at the scaffold surface on the growth and paracrine behavior of mesenchymal stem cells (MSCs) were investigated. The CNPs could improve the proliferation and inhibit the apoptosis of MSCs. Meanwhile, the interaction between the cell membrane and the nanoparticle surface could activate the calcium channel of MSCs leading to the rise of intracellular free Ca(2+) level, which subsequently augments the stability of HIF-1alpha. These chain reactions finally resulted in high expression of angiogenic factor VEGF. The improved paracrine of VEGF could thereby promote the proliferation, differentiation, and tube formation ability of EPCs. Most importantly, in vivo ectopic bone formation experiment demonstrated this method could significantly improve the blood vessel distribution inside of TEB. PMID- 26824827 TI - Copper-Catalyzed N-Arylation of Azoles and Mannich-Type Coupling of Ketones and Azoles under Metal-Free Conditions. AB - A new process has been developed for the copper-catalyzed direct N-arylation of five-membered heterocycles with azoles. Five-membered heterocycles bearing an acetyl group also underwent a Mannich-type reaction with activated azoles to give the corresponding beta-amino ketones under metal-free conditions. These reactions exhibited wide substrate scope, high functional group tolerance, and ease of operation, making them useful tools with numerous potential applications in synthetic chemistry. PMID- 26824826 TI - Risk Factors for Inadequate Defibrillation Safety Margins Vary With the Underlying Cardiac Disease: Implications for Selective Testing Strategies. AB - INTRODUCTION: In view of the shift from routine toward no or selective defibrillation testing, optimization of the current risk stratification for inadequate defibrillation safety margins (DSMs) could improve individualized testing decisions. Given the pathophysiological differences in myocardial substrate between ischemic and nonischemic heart disease (IHD/non-IHD) and the accompanying differences in clinical characteristics, we studied inadequate DSMs and their predictors in relation to the underlying etiology. METHODS AND RESULTS: Cohort of routine defibrillation tests (n = 785) after first implantable cardioverter defibrillator (ICD)-implantations at the Radboud UMC (2005-2014). A defibrillation threshold >25 J was regarded as an inadequate DSM. In total, 4.3% of patients had an inadequate DSM; in IHD 2.5% versus 7.3% in non-IHD (P = 0.002). We identified a group of non-IHD patients at high risk (13-42% inadequate DSM); the remainder of the cohort (>70%) had a risk of only 2% (C-statistic entire cohort 0.74; C-statistic non-IHD 0.82). This was based upon two identified interaction terms: (1) non-IHD and age (aOR 0.94 [95% CI 0.91-0.97]); (2) non-IHD and the indexed left ventricular (LV) internal diastolic diameter (aOR 3.50 [95% CI 2.10-5.82]). CONCLUSION: The present study on risk stratification for an inadequate DSM not only confirms the importance of making a distinction between IHD and non-IHD, but also shows that risk factors in an entire cohort (LV dilatation, age) may only apply to a subgroup (non-IHD). Appreciation of this concept could favorably affect current risk stratification. If confirmed, our approach may be used to optimize individualized testing decisions in an upcoming era of non-routine testing. PMID- 26824828 TI - Evaluation of the C-Terminal Fragment of Entamoeba histolytica Gal/GalNAc Lectin Intermediate Subunit as a Vaccine Candidate against Amebic Liver Abscess. AB - BACKGROUND: Entamoeba histolytica is an intestinal protozoan parasite that causes amoebiasis, including amebic dysentery and liver abscesses. E. histolytica invades host tissues by adhering onto cells and phagocytosing them depending on the adaptation and expression of pathogenic factors, including Gal/GalNAc lectin. We have previously reported that E. histolytica possesses multiple CXXC sequence motifs, with the intermediate subunit of Gal/GalNAc lectin (i.e., Igl) as a key factor affecting the amoeba's pathogenicity. The present work showed the effect of immunization with recombinant Igl on amebic liver abscess formation and the corresponding immunological properties. METHODOLOGY/PRINCIPAL FINDINGS: A prokaryotic expression system was used to prepare the full-length Igl and the N terminal, middle, and C-terminal fragments (C-Igl) of Igl. Vaccine efficacy was assessed by challenging hamsters with an intrahepatic injection of E. histolytica trophozoites. Hamsters intramuscularly immunized with full-length Igl and C-Igl were found to be 92% and 96% immune to liver abscess formation, respectively. Immune-response evaluation revealed that C-Igl can generate significant humoral immune responses, with high levels of antibodies in sera from immunized hamsters inhibiting 80% of trophozoites adherence to mammalian cells and inducing 80% more complement-mediated lysis of trophozoites compared with the control. C-Igl was further assessed for its cellular response by cytokine-gene qPCR analysis. The productions of IL-4 (8.4-fold) and IL-10 (2-fold) in the spleen cells of immunized hamsters were enhanced after in vitro stimulation. IL-4 expression was also supported by increased programmed cell death 1 ligand 1 gene. CONCLUSIONS/SIGNIFICANCE: Immunobiochemical characterization strongly suggests the potential of recombinant Igl, especially the C-terminal fragment, as a vaccine candidate against amoebiasis. Moreover, protection through Th2-cell participation enabled effective humoral immunity against amebic liver abscesses. PMID- 26824829 TI - Diabetes and Cancer. AB - Diabetes and cancer are common conditions, affecting 384 million and 33 million people worldwide, respectively. Therefore, there is great potential for overlap, with people with diabetes also developing cancer and vice versa. However, people with diabetes may be at increased risk of developing cancer when compared with the general population. This is due to both shared risk factors associated with the two diseases and the metabolic derangements associated with diabetes, such as hyperglycaemia, insulin resistance, hyperinsulinaemia and oxidative stress. Glucose-lowering therapies may influence the risk of cancer in people with type 2 diabetes due to these therapies' effects on risk factors that are common to both conditions, including hyperglycaemia and obesity, as well as effects that are specific to the class of drug or drugs. Drugs that reduce circulating insulin levels, such as metformin, may reduce cancer risk, and drugs that increase circulating insulin levels, including exogenous insulin and insulin secretagogues, may increase cancer risk. The influence of glucose-lowering therapies on cancer risk may become an important consideration when selecting glucose-lowering therapies to treat people with type 2 diabetes and a high risk of cancer occurrence or recurrence. PMID- 26824830 TI - Soft and Hard Textured Wheat Differ in Starch Properties as Indicated by Trimodal Distribution, Morphology, Thermal and Crystalline Properties. AB - Starch and proteins are major components in the wheat endosperm that affect its end product quality. Between the two textural classes of wheat i.e. hard and soft, starch granules are loosely bound with the lipids and proteins in soft wheat due to higher expression of interfering grain softness proteins. It might have impact on starch granules properties. In this work for the first time the physiochemical and structural properties of different sized starch granules (A-, B- and C-granules) were studied to understand the differences in starches with respect to soft and hard wheat. A-, B- and C-type granules were separated with >95% purity. Average number and proportion of A-, B-, and C-type granules was 18%, 56%, 26% and 76%, 19%, 5% respectively. All had symmetrical birefringence pattern with varied intensity. All displayed typical A-type crystallites. A-type granules also showed V-type crystallinity that is indicative of starch complexes with lipids and proteins. Granules differing in gelatinization temperature (DeltaH) and transition temperature (DeltaT), showed different enthalpy changes during heating. Substitution analysis indicated differences in relative substitution pattern of different starch granules. Birefringence, percentage crystallinity, transmittance, gelatinization enthalpy and substitution decreased in order of A>B>C being higher in hard wheat than soft wheat. Amylose content decreased in order of A>B>C being higher in soft wheat than hard wheat. Reconstitution experiment showed that starch properties could be manipulated by changing the composition of starch granules. Addition of A-granules to total starch significantly affected its thermal properties. Effect of A-granule addition was higher than B- and C-granules. Transmittance of the starch granules paste showed that starch granules of hard wheat formed clear paste. These results suggested that in addition to differences in protein concentration, hard and soft wheat lines have differences in starch composition also. PMID- 26824831 TI - Sublethal Toxicity Endpoints of Heavy Metals to the Nematode Caenorhabditis elegans. AB - Caenorhabditis elegans, a free-living nematode, is commonly used as a model organism in ecotoxicological studies. The current literatures have provided useful insight into the relative sensitivity of several endpoints, but few direct comparisons of multiple endpoints under a common set of experimental conditions. The objective of this study was to determine appropriate sublethal endpoints to develop an ecotoxicity screening and monitoring system. C. elegans was applied to explore the sublethal toxicity of four heavy metals (copper, zinc, cadmium and chromium). Two physiological endpoints (growth and reproduction), three behavioral endpoints (head thrash frequency, body bend frequency and feeding) and two enzymatic endpoints (acetylcholine esterase [AChE] and superoxide dismutase [SOD]) were selected for the assessment of heavy metal toxicity. The squared correlation coefficients (R2) between the responses observed and fitted by Logit function were higher than 0.90 and the RMSE were lower than 0.10, indicating a good significance statistically. There was no significant difference among the half effect concentration (EC50) endpoints in physiological and behavioral effects of the four heavy metals, indicating similar sensitivity of physiological and behavioral effects. AChE enzyme was more sensitive to copper, zinc, and cadmium than to other physiological and behavioral effects, and SOD enzyme was most sensitive to chromium. The EC50 of copper, zinc, and cadmium, to the AChE enzyme in the nematodes were 0.68 mg/L, 2.76 mg/L, and 0.92 mg/L respectively and the EC50 of chromium to the SOD enzyme in the nematode was 1.58 mg/L. The results of this study showed that there was a good concentration-response relationship between all four heavy metals and the sublethal toxicity effects to C. elegans. Considering these sublethal endpoints in terms of simplicity, accuracy, repeatability and costs of the experiments, feeding is the relatively ideal sublethal toxicity endpoint of heavy metals to C. elegans. PMID- 26824832 TI - Detailed Mechanistic Study of the Non-enzymatic Formation of the Discoipyrrole Family of Natural Products. AB - Discoipyrroles A-D (DPA-DPD) are recently discovered natural products produced by the marine bacterium Bacillus hunanensis that exhibit anticancer properties in vitro. Initial biosynthetic studies demonstrated that DPA is formed in the liquid fermentation medium of B. hunanensis from three secreted metabolites through an unknown but protein-independent mechanism. The increased identification of natural products that depend on non-enzymatic steps creates a significant need to understand how these different reactions can occur. In this work, we utilized (15)N-labeled starting materials and continuous high-sensitivity (1)H-(15)N HMBC NMR spectroscopy to resolve scarce reaction intermediates of the non-enzymatic discoipyrrole reaction as they formed in real time. This information guided supplemental experiments using (13)C- and (18)O-labeled materials to elucidate the details of DPA's non-enzymatic biosynthesis, which features a highly concerted pyrrole formation and necessary O2-mediated oxidation. We have illustrated a novel way of using isotopically enhanced two-dimensional NMR spectroscopy to interrogate reaction mechanisms as they occur. In addition, these findings add to our growing knowledge of how multicomponent non-enzymatic reactions can occur through inherently reactive bacterial metabolites. PMID- 26824835 TI - Another year, another success. PMID- 26824833 TI - Three-Dimensional Hysterosalpingo-Contrast-Sonography for the Assessment of Tubal Patency in Women with Infertility: A Systematic Review with Meta-Analysis. AB - BACKGROUND/AIMS: We aimed at performing a systematic review to determine the diagnostic accuracy of three-dimensional (3D) hysterosalpingo-contrast-sonography (HyCoSy) for detecting tubal occlusion. METHODS: A systematic review in Medline database search from January 1989 to October 2015 to identify relevant studies evaluating 3D-HyCoSy. Eligibility criteria were studies assessing the role of 3D HyCoSy for diagnosing tubal occlusion in infertile women. Index test was 3D HyCoSy. Reference standard was laparoscopy with dye test or X-ray hysterosalpingography. Quality was assessed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled sensitivity and specificity for the method were estimated. RESULTS: A total number of 88 papers were identified. After exclusions, nine studies were ultimately included. Pooled estimated sensitivity was 98% (95% CI 91-100) with a moderate heterogeneity (I2: 64.8%, 95% CI 39.6-89.9; and Cochran Q 22.7, p < 0.001). Pooled estimated specificity was 90% (95% CI 83-95) with significant heterogeneity (I2: 80.3%, 95% CI 68.1-92.5; and Cochran Q 40.6, p < 0.001). Positive likelihood ratio was 10.3 (95% CI 5.6 18.7) and negative likelihood ratio was 0.02 (95% CI 0.00-0.21). CONCLUSION: 3D HyCoSy is an accurate test for diagnosing tubal occlusion in women with infertility. PMID- 26824837 TI - Barriers to NP Practice that Impact Healthcare Redesign. AB - As healthcare reform evolves, nurse practitioners (NP) will play key roles in improving health outcomes of diverse populations. According to the Institute of Medicine (IOM) 2011 report, The Future of Nursing: Leading Change Advancing Health, nurses should be change advocates by caring for populations within complex healthcare systems. The IOM reports asserts, "advanced practice registered nurses (APRNs) should be able to practice to the fullest extent of their education and training" (IOM, 2011, s8). However, existing barriers in the healthcare arena limit APRN practice. This article will discuss some of these barriers and provide suggestions for possible ways to decrease the barriers. PMID- 26824838 TI - The Affordable Care Act: Primary Care and the Doctor of Nursing Practice Nurse. AB - The passage of the 2010 Patient Protection and Affordable Care Act (ACA) initiated the transformation of the United States healthcare system. The ACA fosters a preventive healthcare model that emphasizes primary care, funds community health initiatives, and promotes quality care. These changes increase the need for well-prepared healthcare professionals. Advanced Practice Registered Nurses (APRNs) who hold the Doctor of Nursing Practice (DNP) degree are prepared to meet this increased need by providing leadership in community health centers, serving on interdisciplinary teams, and advocating for and directing future policy initiates. In this article, the authors consider how the ACA will serve as a prevention model, describe the role of DNP nurses as primary care providers, explain how preventive healthcare can be enhanced through the use of a primary care model, and address associated challenges related to increasing preventive care in our healthcare system. They also discuss DNP nurse leadership opportunities related to community-based programs and policy strategies to strengthen primary care delivery. The authors conclude by noting the professional and legal barriers that need to be removed before DNP nurses will be able to provide the care they have been prepared to offer. PMID- 26824840 TI - Light and electron microscopic study of mature spermatozoa from White Pekin duck (Anas platyrhynchos): an ultrastructural and molecular analysis. AB - The morphology, ultrastructure, and functions of mature avian spermatozoa have been of immense commercial and scientific interest for several reasons. This is mainly important in case of birds in poultry production, conservation, and in the use of sperm morphometry as phylogenetic evidence. Avian spermatozoa share complex or no correlation of sperm morphometry with respect to testis and/or body size as described before. In this work, we have isolated mature spermatozoa from White Pekin duck (Anas platyrhynchos) by non-invasive methods and performed several immunostaining analysis as well as cytochemical analysis using electron and light microscopes. Here, we report the presence of different post translationally modified tubulin such as tyrosinated-, detyrosinated-, acetylated , polyglutamylated-, and glycylated-tubulin in specific regions of the mature spermatozoa. By using field-emission scanning electron microscope, we confirm the presence of acrosome-like structure at the tip of the sperm head. However, this structure remains non-reactive to common lectins such as Peanut Agglutinin (PNA) and cholesterol-sensitive dyes such as Filipin. We report that this acrosomal structure is primarily made of lipid-based structures and is resistant to 0.1% Triton X100. Confocal microscopy and super resolution structured illumination microscopy study indicates that the nucleus is bifurcated at the tip region. By using specific markers, we report that the perforatorium structure present at the tip of the spermatozoa head contains specialized organelles that is similar to atypical mitochondria. We propose that these ultrastructural and molecular parameters can be used as species-specific features. The bifurcated nucleus and presence of atypical mitochondria within this structure may be relevant for the complex mitochondrial inheritance and mitochondrial heteroplasmy observed in case of avian population. PMID- 26824839 TI - Colocalization of the (Pro)renin Receptor/Atp6ap2 with H+-ATPases in Mouse Kidney but Prorenin Does Not Acutely Regulate Intercalated Cell H+-ATPase Activity. AB - The (Pro)renin receptor (P)RR/Atp6ap2 is a cell surface protein capable of binding and non-proteolytically activate prorenin. Additionally, (P)RR is associated with H(+)-ATPases and alternative functions in H(+)-ATPase regulation as well as in Wnt signalling have been reported. Kidneys express very high levels of H(+)-ATPases which are involved in multiple functions such as endocytosis, membrane protein recycling as well as urinary acidification, bicarbonate reabsorption, and salt absorption. Here, we wanted to localize the (P)RR/Atp6ap2 along the murine nephron, exmaine whether the (P)RR/Atp6ap2 is coregulated with other H(+)-ATPase subunits, and whether acute stimulation of the (P)RR/Atp6ap2 with prorenin regulates H(+)-ATPase activity in intercalated cells in freshly isolated collecting ducts. We localized (P)PR/Atp6ap2 along the murine nephron by qPCR and immunohistochemistry. (P)RR/Atp6ap2 mRNA was detected in all nephron segments with highest levels in the collecting system coinciding with H(+) ATPases. Further experiments demonstrated expression at the brush border membrane of proximal tubules and in all types of intercalated cells colocalizing with H(+) ATPases. In mice treated with NH4Cl, NaHCO3, KHCO3, NaCl, or the mineralocorticoid DOCA for 7 days, (P)RR/Atp6ap2 and H(+)-ATPase subunits were regulated but not co-regulated at protein and mRNA levels. Immunolocalization in kidneys from control, NH4Cl or NaHCO3 treated mice demonstrated always colocalization of PRR/Atp6ap2 with H(+)-ATPase subunits at the brush border membrane of proximal tubules, the apical pole of type A intercalated cells, and at basolateral and/or apical membranes of non-type A intercalated cells. Microperfusion of isolated cortical collecting ducts and luminal application of prorenin did not acutely stimulate H(+)-ATPase activity. However, incubation of isolated collecting ducts with prorenin non-significantly increased ERK1/2 phosphorylation. Our results suggest that the PRR/Atp6ap2 may form a complex with H(+)-ATPases in proximal tubule and intercalated cells but that prorenin has no acute effect on H(+)-ATPase activity in intercalated cells. PMID- 26824841 TI - Characterization and Mechanism for the Protection of Photolytic Decomposition of N-Halamine Siloxane Coatings by Titanium Dioxide. AB - N-Halamine antibacterial materials have superior inactivation activities due to oxidative chlorine species. However, N-Cl bonds and bonds between N-halamine and substrates often decompose rapidly under UV irradiation, leading to unrecoverable loss of antimicrobial activity. In this study, titanium dioxide was covalently bonded onto N-halamine siloxane poly[5,5-dimethyl-3-(3' triethoxysilylpropyl)hydantoin] (PSPH) via a sol-gel process. Experimental testing of the chlorinated cotton fabrics treated with TiO2/PSPH demonstrated that the residual oxidative chlorine in cotton-TiO2/PSPH-Cl was still effective for inactivating bacteria after 50 washing cycles and under UV light irradiation for 24 h. Quantum mechanical calculations found that TiO2 improves the UV stability of the PSPH-Cl system by increasing the activation barrier of the C-Si scission reaction responsible for the loss of the biocidal hydantoin moiety. SEM, XPS and FTIR spectra were used to characterize the coated cotton samples. Cotton TiO2/PSPH-Cl samples exhibited good antibacterial activity against Staphylococcus aureus (ATCC 6538) and Escherichia coli O157:H7 (ATCC 43895). The storage stability and washing stability of treated cotton fabrics were also investigated. PMID- 26824842 TI - Outcomes of three sling procedures at the time of abdominal sacral colpopexy. AB - INTRODUCTION: A sling at time of sacral colpopexy (SCP) for apical pelvic organ prolapse (POP) is valuable in the treatment of overt, urodynamic, and occult stress urinary incontinence (SUI). As there is no current agreement regarding the optimal choice of sling in these women, we compare the outcomes of three sling procedures in this population: autologous rectus fascia bladder neck sling (ARF), retropubic midurethral sling (RPM), and transobturator midurethral sling (TOM). METHODS: We performed a retrospective single institution, single-surgeon review of data identifying women with minimum follow-up of 12 months who underwent a concomitant sling and SCP following urodynamics with and without POP reduction. Preoperative and postoperative evaluation included objective and subjective assessment. Cure required absence of subjective and objective SUI. RESULTS: Out of 187 women, 152 (81%) met inclusion criteria (49 ARF, 58 RPM, and 45 TOM). There were no significant differences among sling groups regarding demographics. SUI cure rates were not significantly different between sling groups, or within each group after stratification by overt and occult SUI. QoL indices improved significantly after surgery for the entire cohort. CONCLUSIONS: All three sling types appear to produce similar cure rates of SUI when done concomitantly with SCP. There did not appear to be any significant differences when stratified by occult or overt SUI. No sling type was associated with more postoperative complications. Larger studies are necessary to confirm the findings of this single-institution, retrospective study. Neurourol. Urodynam. 36:482-485, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26824843 TI - In-Silico Computing of the Most Deleterious nsSNPs in HBA1 Gene. AB - BACKGROUND: alpha-Thalassemia (alpha-thal) is a genetic disorder caused by the substitution of single amino acid or large deletions in the HBA1 and/or HBA2 genes. METHOD: Using modern bioinformatics tools as a systematic in-silico approach to predict the deleterious SNPs in the HBA1 gene and its significant pathogenic impact on the functions and structure of HBA1 protein was predicted. RESULTS AND DISCUSSION: A total of 389 SNPs in HBA1 were retrieved from dbSNP database, which includes: 201 non-coding synonymous (nsSNPs), 43 human active SNPs, 16 intronic SNPs, 11 mRNA 3' UTR SNPs, 9 coding synonymous SNPs, 9 5' UTR SNPs and other types. Structural homology-based method (PolyPhen) and sequence homology-based tool (SIFT), SNPs&Go, PROVEAN and PANTHER revealed that 2.4% of the nsSNPs are pathogenic. CONCLUSIONS: A total of 5 nsSNPs (G60V, K17M, K17T, L92F and W15R) were predicted to be responsible for the structural and functional modifications of HBA1 protein. It is evident from the deep comprehensive in silico analysis that, two nsSNPs such as G60V and W15R in HBA1 are highly deleterious. These "2 pathogenic nsSNPs" can be considered for wet-lab confirmatory analysis. PMID- 26824844 TI - Opioid Use and Storage Patterns by Patients after Hospital Discharge following Surgery. AB - INTRODUCTION: Opioid-based analgesic therapy represents a cornerstone of pain management after surgery. The recent rise in opioid sales and opioid overdoses suggests it is important to maximize the safety of opioid prescribing after surgery. Given that patients may live with other family members in the home, safe storage and appropriate disposal of excess opioids after hospital discharge are necessary to prevent unintended secondary exposures. Identifying characteristics of patients who are likely to be prescribed excess opioids after surgery may enable more targeted prescription practices and safety interventions. Our study aimed to elucidate patient-reported opioid use patterns and modes of home storage of opioids among patients discharged home after Cesarean section (C-section) and thoracic surgery. Specifically, we sought to identify characteristics of patients who reported using about half or more versus less of the opioids prescribed to them for use after hospital discharge. METHODS: For this cohort study, we developed a survey on quality of analgesia following hospital discharge, amounts of opioids taken relative to the amount prescribed, reasons for not taking all prescribed medications, and storage and disposal methods for leftover opioids. Adult patients, who had C-section or thoracic surgery at a tertiary academic medical center, were given a web-based self-administered survey after discharge. Descriptive statistics (means and standard deviations, proportions) were used to describe the study sample and survey results. Comparisons between patients who reported taking about half or more versus less of the opioids prescribed to them for use after hospital discharge were made using unpaired t-tests, Mann-Whitney tests, and Chi-square tests as appropriate. RESULTS: The majority (53%) of respondents after C-section (N = 30) reported taking either no or very few (less than 5) prescribed opioid pills; 83% reported taking half or less; and 17% of women, reported taking all or nearly all (5 or fewer pills left over) of their opioid prescription. In a cohort of patients after thoracic surgery (n = 31) 45% reported taking either no or very few (5 or less) prescribed opioid pills; 71% reported taking half or less; and 29% of patients reported taking all or nearly all (5 or fewer pills left over) of their opioid prescription. In both cohorts, use of opioids while hospitalized was higher in the group reporting using about half or more of prescribed opioids after discharge. Leftover opioids were stored in an unlocked location in 77% and 73% of cases following C-section and thoracic surgery, respectively. CONCLUSION: Our findings from surveys in two distinct patient populations at a single academic medical center suggest that current opioid prescribing practices for pain management at hospital discharge following Cesarean section and thoracic surgery may not account for individual patients' analgesic requirements. Excess opioid pills are commonly stored in unsecured locations and represent a potential source for non-medical opioid use and associated morbidity and mortality in patients and their families. Research to develop goal-directed and patient-centered post-discharge opioid prescription practices and encourage opioid safety practices after surgery is needed. PMID- 26824845 TI - Widefield Two-Photon Excitation without Scanning: Live Cell Microscopy with High Time Resolution and Low Photo-Bleaching. AB - We demonstrate fluorescence imaging by two-photon excitation without scanning in biological specimens as previously described by Hwang and co-workers, but with an increased field size and with framing rates of up to 100 Hz. During recordings of synaptically-driven Ca(2+) events in primary rat hippocampal neurone cultures loaded with the fluorescent Ca(2+) indicator Fluo-4 AM, we have observed greatly reduced photo-bleaching in comparison with single-photon excitation. This method, which requires no costly additions to the microscope, promises to be useful for work where high time-resolution is required. PMID- 26824846 TI - Utility of Pediatric Appendicitis Score in Female Adolescent Patients. AB - OBJECTIVES: Acute appendicitis is common in the pediatric population and is difficult to diagnose in adolescent females. The validated Pediatric Appendicitis Score (PAS) has unclear utility in female adolescents. The purpose of this study is to determine the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the PAS for female adolescents compared to all other patients. METHODS: This study examined a retrospective observational cohort of patients ages 3 to 21 years in a pediatric emergency department with prospectively assigned PAS from an existing database. We compared the sensitivity, specificity, PPV, and NPV of the PAS for acute appendicitis among female adolescent patients (13 to 21 years) and all other patients. RESULTS: Of the 1,228 patients enrolled, 901 (73.4%) had a complete PAS. Among the 901 patients, 249 (27.6%) had pathology-proven appendicitis, 494 (54.8%) were female, and 272 (30.2%) were adolescent females. At a cutoff of >=8, the PAS showed a specificity of 89% for adolescent females and 78% for all other patients (p < 0.001), although the specificities did not differ at a cutoff of >=7. At both cutoffs, the PPVs were poor in both groups. At a cutoff of >=3, the PAS showed similar sensitivities in both groups. At a cutoff of <3, the NPVs did not significantly differ between groups. CONCLUSION: At a cutoff of >=8 (although not >=7), the PAS demonstrated a higher specificity among female adolescents compared to all other patients. The PPV for both cutoffs in both groups were poor. At a cutoff of >=3, sensitivities were equivalent. The NPV for a cutoff of <3 was acceptable but similar in both groups. While sensitivities were similar to previously reported, specificities in both groups were lower. This highlights the need for further investigation of the PAS's performance in specific subpopulations. PMID- 26824847 TI - Modelization of the Current and Future Habitat Suitability of Rhododendron ferrugineum Using Potential Snow Accumulation. AB - Mountain areas are particularly sensitive to climate change. Species distribution models predict important extinctions in these areas whose magnitude will depend on a number of different factors. Here we examine the possible impact of climate change on the Rhododendron ferrugineum (alpenrose) niche in Andorra (Pyrenees). This species currently occupies 14.6 km2 of this country and relies on the protection afforded by snow cover in winter. We used high-resolution climatic data, potential snow accumulation and a combined forecasting method to obtain the realized niche model of this species. Subsequently, we used data from the high resolution Scampei project climate change projection for the A2, A1B and B1 scenarios to model its future realized niche model. The modelization performed well when predicting the species's distribution, which improved when we considered the potential snow accumulation, the most important variable influencing its distribution. We thus obtained a potential extent of about 70.7 km(2) or 15.1% of the country. We observed an elevation lag distribution between the current and potential distribution of the species, probably due to its slow colonization rate and the small-scale survey of seedlings. Under the three climatic scenarios, the realized niche model of the species will be reduced by 37.9-70.1 km(2) by the end of the century and it will become confined to what are today screes and rocky hillside habitats. The particular effects of climate change on seedling establishment, as well as on the species' plasticity and sensitivity in the event of a reduction of the snow cover, could worsen these predictions. PMID- 26824848 TI - Sofosbuvir-based treatment is safe and effective in patients with chronic hepatitis C infection and end stage renal disease: a case series. AB - BACKGROUND & AIMS: Interferon and ribavirin-free regimens to treat chronic hepatitis C virus (HCV) infection in patients with end stage renal disease are not approved and represent an area of unmet clinical need. We report our experience on the safety and efficacy of sofosbuvir/simeprevir and sofosbuvir/ledipasvir therapy in patients on haemodialysis. METHODS: Patients with chronic HCV infection on haemodialysis were included in this study. Patients were started on either sofosbuvir/simeprevir or sofosbuvir/ledipasvir. Routine clinical and laboratory data were collected at baseline and during treatment. The primary outcome was sustained virological response at week 12 (SVR12). RESULTS: Eight patients with mean age 56.8 +/- 20 years were included in this study. Seven were treatment naive and one was a priori null responder to interferon-based therapy. Four patients were started on sofosbuvir/simeprevir and four on sofosbuvir/ledipasvir for 12 weeks. Therapy was well tolerated overall with nausea/vomiting, pruritus, headache and a 2 g/dl drop in haemoglobin developing in one patient each. No patient discontinued therapy because of side effects. Comparison of labs at baseline and nadir levels during treatment revealed no significant change in haemoglobin (10.8 +/- 2.4 g/dl vs 10.3 +/- 1.6 g/dl), platelet count (198 +/- 164 k/MUl vs 184.5 +/- 162/MUl) and bilirubin (0.3 +/- 0.4 mg/dl vs 0.25 +/- 0.15 mg/dl). Eight of eight patients had undetectable HCV RNA at the end of treatment. One patient was lost to follow up and the remaining seven achieved SVR12. CONCLUSION: Full dose sofosbuvir/simeprevir or sofosbuvir/ledipasvir therapy for HCV-infected patients with end stage renal disease was well tolerated with no discontinuation owing to side effects and no significant adverse events. PMID- 26824849 TI - Intraocular Pressure Reduction Is Associated with Reduced Venous Pulsation Pressure. AB - PURPOSE: To explore whether alterations in intraocular pressure (IOP) affect vein pulsation properties using ophthalmodynamometric measures of vein pulsation pressure. PATIENTS AND METHODS: Glaucoma patients had two retinal vein pulsation pressure (VPP) measurements from upper and lower hemiveins performed by ophthalmodynamometry at least 3 months apart. All subjects had VPP and IOP recorded at two visits, with standard automated perimetry, central corneal thickness (CCT) recorded at the initial visit. Where venous pulsation was spontaneous ophthalmodynamometry could not be performed and VPP was considered equal to IOP. Change in VPP was calculated and binarized with reduction in pressure scored 1 and no change or increase scored as 0. Data analysis used a mixed logistic regression model with change in VPP as response variable and change in IOP, visual field loss (mean deviation), CCT and time interval as explanatory variables. RESULTS: 31 subjects (20 females) with mean age 60 years (sd 11) were examined with change in VPP being significantly associated with change in IOP (odds ratio 1.6/mmHg, 95% CI 1.2 to 2.1 in the glaucoma patients but not suspect patients (p = 0.0005). CONCLUSION: Change in VPP is strongly associated with change in IOP such that a reduced intraocular pressure is associated with a subsequent reduction in VPP. This indicates that reduced IOP alters some retinal vein properties however the nature and time course of these changes is not known. PMID- 26824852 TI - Methods Factors In Multitrait-Multimethod Matrices : Multiplicative Rather Than Additive? AB - When traits are measured by the same method (or at the same time) the intertrait correlations are higher than when the intertrait correlation is across methods. An empirical investigation of the nature of such method factors is reported, in which the method factors seem to operate in a multiplicative rather than additive way, or in which larger method loadings are associated with larger trait loadings. An implicit-theory-of-personality explanation is offered for the case of ratings as methods. An attenuation model has more general applicability to the oases illustrated. The possibility is raised that the finding, if confirmed in other domains, demonstrates a fundamental innappropriateness of factor analysis for the componential analysis of indi6dual differences data. PMID- 26824850 TI - Three-Dimensional Imaging of the Intracellular Fate of Plasmid DNA and Transgene Expression: ZsGreen1 and Tissue Clearing Method CUBIC Are an Optimal Combination for Multicolor Deep Imaging in Murine Tissues. AB - Evaluation methods for determining the distribution of transgene expression in the body and the in vivo fate of viral and non-viral vectors are necessary for successful development of in vivo gene delivery systems. Here, we evaluated the spatial distribution of transgene expression using tissue clearing methods. After hydrodynamic injection of plasmid DNA into mice, whole tissues were subjected to tissue clearing. Tissue clearing followed by confocal laser scanning microscopy enabled evaluation of the three-dimensional distribution of transgene expression without preparation of tissue sections. Among the tested clearing methods (ClearT2, SeeDB, and CUBIC), CUBIC was the most suitable method for determining the spatial distribution of transgene expression in not only the liver but also other tissues such as the kidney and lung. In terms of the type of fluorescent protein, the observable depth for green fluorescent protein ZsGreen1 was slightly greater than that for red fluorescent protein tdTomato. We observed a depth of ~1.5 mm for the liver and 500 MUm for other tissues without preparation of tissue sections. Furthermore, we succeeded in multicolor deep imaging of the intracellular fate of plasmid DNA in the murine liver. Thus, tissue clearing would be a powerful approach for determining the spatial distribution of plasmid DNA and transgene expression in various murine tissues. PMID- 26824853 TI - The Effect Of Shifts In Fixed-Interval Schedules On Acquisition, Extinction, Spontaneous Recovery, And Reacquisition. AB - Using both multivariate and univariate statistical tests, the effect of two opposite patterns of primary reinforcement schedules upon the acquisition, extinction, spontaneous recovery and reacquisition of bar pressing was determined. Two control and two experimental groups, each consisting of eight Ss, formed the standard 2x2 factorial design for the experiment. The main effects were (a) effect of primary reinforcement (experimental vs. control groups) and (b) direction of shift in the schedule values (ascending vs. descending groups). The extinction data showed that the experimental group exposed to the ascending order shift pressed the bar more than the descending group. Therefore, persistence of nonreinforced responding is a function of the direction of shift in fixed-interval values. The recovery data for first day indicated that primary reinforcements following either pattern facilitated spontaneous recovery. However, on second day neither direction of shift nor primary reinforcement had any significant effect on it. Covariance analysis of recovery and reacquisition data for second day revealed that the experimental ascending group showed better recovery and reacquisition when the frequency of prior nonreinforced responding was held constant. The SL analyses suggest a higher acquisition level for the experimental ascending group than for the other groups. It is possible to explain the result in terms of Hull's habit- strength theory. PMID- 26824851 TI - Comparison of the Dynesys Dynamic Stabilization System and Posterior Lumbar Interbody Fusion for Lumbar Degenerative Disease. AB - BACKGROUND: There have been few studies comparing the clinical and radiographic outcomes between the Dynesys dynamic stabilization system and posterior lumbar interbody fusion (PLIF). The objective of this study is to compare the clinical and radiographic outcomes of Dynesys and PLIF for lumbar degenerative disease. METHODS: Of 96 patients with lumbar degenerative disease included in this retrospectively analysis, 46 were treated with the Dynesys system and 50 underwent PLIF from July 2008 to March 2011. Clinical and radiographic outcomes were evaluated. We also evaluated the occurrence of radiographic and symptomatic adjacent segment degeneration (ASD). RESULTS: The mean follow-up time in the Dynesys group was 53.6 +/- 5.3 months, while that in the PLIF group was 55.2 +/- 6.8 months. At the final follow-up, the Oswestry disability index and visual analogue scale score were significantly improved in both groups. The range of motion (ROM) of stabilized segments in Dynesys group decreased from 7.1 +/- 2.2 degrees to 4.9 +/- 2.2 degrees (P < 0.05), while that of in PLIF group decreased from 7.3 +/- 2.3 degrees to 0 degrees (P < 0.05). The ROM of the upper segments increased significantly in both groups at the final follow-up, the ROM was higher in the PLIF group. There were significantly more radiographic ASDs in the PLIF group than in the Dynesys group. The incidence of complications was comparable between groups. CONCLUSIONS: Both Dynesys and PLIF can improve the clinical outcomes for lumbar degenerative disease. Compared to PLIF, Dynesys stabilization partially preserves the ROM of the stabilized segments, limits hypermobility in the upper adjacent segment, and may prevent the occurrence of ASD. PMID- 26824854 TI - The Stability Of The Wisc Factor Structure At Three Age Levels. AB - The WISC, Peabody Picture Vocabulary Test, and Ammons' Full Range Picture Vocabulary Test were administered to a sample of 216 children three times: at pre school, first grade, and third grade levels. The sample included 91 Negro children and 126 white children. Twenty-six variables were developed from the 11 WISC tests to form as many variables as possible so that a total of 28 variables was analyzed in the study. The variables were factor analyzed a t each level of testing and the three sets of factor scores were canonically correlated. In general, more common factors were obtained at the lower levels and a more general Verbal factor was determined at the third grade level. The battery test-retest reliability was -86. PMID- 26824855 TI - Predicting Group Differences In Cluster Analysis: The Social Area Problem. AB - Prediction of group differences by cluster analysis procedures is described for the case of neighborhoods (tracts) of a metropolitan area. Social areas of homogeneous neighborhoods are isolated by objective "O-analysis" procedures of the BC TRY Computer System. The predictor attributes are pre-war demographic features from which high predictions both of demographic and voting-attitudes are made up to 15 years, despite the social disruptions of a great war. Three basic dimensions, Conservatism, Territoriality, and Exclusiveness are found to predict all demographic and attitudinal characteristics of neighborhoods over a decade and a half. PMID- 26824856 TI - Multivariate Analysis Of A Rehabilitation System : Cross Validation And Extension. AB - Cross-validation of previously published findings regarding the structure of rehabilitation data yields substantial evidence that this structure is stable and quite definitive. Tentative data are presented regarding relation- ships between intelligence and personality on the one hand, and rehabilitation outcomes on the other. It appears that intelligence is more related to short- run outcomes; personality more related to long-run outcomes. PMID- 26824857 TI - Nonmetric Factor Analysis: A Rank Reducing Alternative To Linear Factor Analysis. PMID- 26824859 TI - Group Based Pattern Analysis Of The Single Individual. AB - This paper shows how the personality structure of a single individual can be statistically: analyzed into its component types (or factors) as these are reflected in responses which he has in common with a sample of subjects (chosen to be representative of a universe to which the single subject belongs). A further development expands the method to show how patterns can be selected in an effort to differentiate categories of individuals in a fashion similar to the manner in which items are sought to accomplish the same goal. PMID- 26824858 TI - A Discrimination Model For Multivariate Q Representations. AB - The proposed discrimination model for Q representation is a generalization of the method of unfolding in an algebraic rather than a geometric field. Placements of Q statements relative to one another in joint space so as to form a quasi-normal distribution of the q stimulus items are assigned Q values which form a bounded set of symbols with specified order in arithmetic progression; for example, a finite set from "one" to "nine" wherein "five" is the midpoint of an ordered metric within persons. An algebraic theory of numbers permits mathematical operations to be carried out with sets of sets of such symbols. Using illustrative data, a mathematical model is developed for the analysis of Q values, each of which represents the intersect of two or more dimensions of behavior structured into a Q set, and for testing its stability, consistency, and reliability. The Q check procedures permit comparisons among individuals and subsamples of population samples. PMID- 26824860 TI - The Reliability And Consistency Of Complex Personality Judgements. AB - Two separate tasks were used to investigate the ability of subjects to make reliable and consistent judgments of similarities among personalities. Ten social categories for which each subject specified persons known to him- self were used as concepts. Test-retest reliabilities were obtained for an 8 point similarity dissimilarity scale and inconsistency was measured by the intransitive relations appearing in a triadic judgment test. Reliabilities and consistencies were judged sufficiently adequate for use of these types of judgments in a multidimensional scaling approach t o individual differences in social perception. PMID- 26824861 TI - Correction: Quercetin Influences Quorum Sensing in Food Borne Bacteria: In-Vitro and In-Silico Evidence. PMID- 26824862 TI - Non-invasive prenatal diagnosis of Duchenne and Becker muscular dystrophies by relative haplotype dosage. AB - OBJECTIVE: Development of an accurate and affordable test for the non-invasive prenatal diagnosis of Duchenne and Becker muscular dystrophies (DMD/BMD) to implement in clinical practice. METHOD: Cell-free DNA was extracted from maternal blood and prepared for massively parallel sequencing on an Illumina MiSeq by targeted capture enrichment of single nucleotide polymorphisms (SNPs) across the dystrophin gene on chromosome X. Sequencing data were analysed by relative haplotype dosage. RESULTS: Seven healthy pregnant donors and two pregnant DMD carriers all bearing a male fetus were recruited through the non-invasive prenatal diagnosis for single gene disorders study. Non-invasive prenatal diagnosis testing was conducted by relative haplotype dosage analysis for X linked disorders where the genomic DNA from the chorionic villus sampling (for healthy pregnant donors) or from the proband (for pregnant DMD carriers) was used to identify the reference haplotype. Results for all patients showed a test accuracy of 100%, when the calculated fetal fraction was >4% and correlated with known outcomes. A recombination event was also detected in a DMD patient. CONCLUSION: Our new test for NIPD of DMD/BMD has been shown to be accurate and reliable during initial stages of validation. It is also feasible for implementation into clinical service. PMID- 26824864 TI - Comparison of O-Antigen Gene Clusters of All O-Serogroups of Escherichia coli and Proposal for Adopting a New Nomenclature for O-Typing. AB - Escherichia coli strains are classified based on O-antigens that are components of the lipopolysaccharide (LPS) in the cell envelope. O-antigens are important virulence factors, targets of both the innate and adaptive immune system, and play a role in host-pathogen interactions. Because they are highly immunogenic and display antigenic specificity unique for each strain, O-antigens are the biomarkers for designating O-types. Immunologically, 185 O-serogroups and 11 OX groups exist for classification. Conventional serotyping for O-typing entails agglutination reactions between the O-antigen and antisera generated against each O-group. The procedure is labor intensive, not always accurate, and exhibits equivocal results. In this report, we present the sequences of 71 O-antigen gene clusters (O-AGC) and a comparison of all 196 O- and OX-groups. Many of the designated O-types, applied for classification over several decades, exhibited similar nucleotide sequences of the O-AGCs and cross-reacted serologically. Some O-AGCs carried insertion sequences and others had only a few nucleotide differences between them. Thus, based on these findings, it is proposed that several of the E. coli O-groups may be merged. Knowledge of the O-AGC sequences facilitates the development of molecular diagnostic platforms that are rapid, accurate, and reliable that can replace conventional serotyping. Additionally, with the scientific knowledge presented, new frontiers in the discovery of biomarkers, understanding the roles of O-antigens in the innate and adaptive immune system and pathogenesis, the development of glycoconjugate vaccines, and other investigations, can be explored. PMID- 26824863 TI - Sphingosine-1-Phosphate Induces Dose-Dependent Chemotaxis or Fugetaxis of T-ALL Blasts through S1P1 Activation. AB - Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in several physiological processes including cell migration and differentiation. S1P signaling is mediated through five G protein-coupled receptors (S1P1-S1P5). S1P1 is crucial to the exit of T-lymphocytes from the thymus and peripheral lymphoid organs through a gradient of S1P. We have previously observed that T-ALL and T LBL blasts express S1P1. Herein we analyzed the role of S1P receptors in the migratory pattern of human T-cell neoplastic blasts. S1P-triggered cell migration was directly related to S1P1 expression. T-ALL blasts expressing low levels of S1P1 mRNA (HPB-ALL) did not migrate toward S1P, whereas those expressing higher levels of S1P1 (MOLT-4, JURKAT and CEM) did migrate. The S1P ligand induced T-ALL cells chemotaxis in concentrations up to 500 nM and induced fugetaxis in higher concentrations (1000-10000 nM) through interactions with S1P1. When S1P1 was specifically blocked by the W146 compound, S1P-induced migration at lower concentrations was reduced, whereas higher concentrations induced cell migration. Furthermore, we observed that S1P/S1P1 interactions induced ERK and AKT phosphorylation, and modulation of Rac1 activity. Responding T-ALL blasts also expressed S1P3 mRNA but blockage of this receptor did not modify migratory responses. Our results indicate that S1P is involved in the migration of T ALL/LBL blasts, which is dependent on S1P1 expression. Moreover, S1P concentrations in the given microenvironment might induce dose-dependent chemotaxis or fugetaxis of T-ALL blasts. PMID- 26824866 TI - Correction: Detection and Characterization of Metastatic Cancer Cells in the Mesogastrium of Gastric Cancer Patients. PMID- 26824865 TI - FoxC2 Enhances BMP7-Mediated Anabolism in Nucleus Pulposus Cells of the Intervertebral Disc. AB - Bone-morphogenetic protein-7 (BMP-7) is a growth factor that plays a major role in mediating anabolism and anti-catabolism of the intervertebral disc matrix and cell homeostasis. In osteoblasts, Forkhead box protein C2 (FoxC2) is a downstream target of BMPs and promotes cell proliferation and differentiation. However, the role FoxC2 may play in degenerative human intervertebral disc tissue and the relationship between FoxC2 and BMP-7 in nucleus pulposus (NP) cells remain to be elucidated. This study aims to investigate the presence and signaling mechanisms of FoxC2 in degenerative human intervertebral disc tissue and NP cells. Western blot and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses were used to measure FoxC2 expression in the NP tissue and cells. Transfections were carried out to measure the effect of FoxC2 on BMP-7 mediated extracellular matrix upregulation. Adenoviral knock-down of Smad1 was performed to investigate the mechanism of BMP-7-induced FoxC2 expression. In degenerative NP tissue, FoxC2 was markedly upregulated and positively correlated with increased disc degeneration. Induction of NP cell proliferation was confirmed by using cell counting kit-8 assay, immunocytochemistry and real-time qRT-PCR for Ki67. FoxC2 led to decreased noggin expression and increased Smad1/5/8 phosphorylation. During combined treatment with BMP-7, FoxC2 greatly potentiated anabolism through synergistic mechanisms on ECM formation. Combination therapy using BMP-7 and FoxC2 may be beneficial to the treatment of intervertebral disc degeneration. PMID- 26824867 TI - Heterogeneity in Primary Productivity Influences Competitive Interactions between Red Deer and Alpine Chamois. AB - Habitat heterogeneity can promote coexistence between herbivores of different body size limited to different extents by resource quantity and quality. Red deer (Cervus elaphus) are known as superior competitors to smaller species with similar diets. We compared competitive interactions and habitat use between red deer and Alpine chamois (Rupicapra rupicapra) in two adjacent valleys in a strictly protected area in the Central Alps. Red deer density was higher in the valley with higher primary productivity. Only here was horn growth in kid and yearling chamois (as a measure for body condition) negatively correlated with red deer population size, suggesting interspecific competition, and chamois selected meadows with steeper slopes and lower productivity than available on average. Conversely, red deer selected meadows of high productivity, particularly in the poorer area. As these were located mainly at lower elevations, this led to strong altitudinal segregation between the two species here. Local differences in interspecific competition thus coincided with differences in habitat preference and-segregation between areas. This suggests that spatial habitat and resource heterogeneity at the scale of adjacent valleys can provide competition refuges for competitively inferior mountain ungulates which differ from their superior competitor in their metabolic requirements. PMID- 26824869 TI - Treatment Goals in Diabetes. AB - The quality of glycaemic control in diabetes mellitus relies on accurate individualization of available treatment options. Treatment targets depend on the type and duration of diabetes, the patients' abilities and characteristics and the individual risk for acute and/or late-stage complications. These complications include hypoglycaemia, which can be severe and life threatening, hyperglycaemia, which is a main factor for the development of cardiovascular disease, and macrovascular and microvascular disease, both of which are hallmark features of diabetes-associated constraints. Moreover, other treatment goals in diabetic patients influence both glycaemic control and quality of life. Lipoproteins, blood pressure, weight control, mental health and lifestyle are important factors that contribute to the frequency of diabetes-associated complications. PMID- 26824870 TI - Development of stem cell-based therapies for Parkinson's disease. AB - Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons of the substantia nigra pars compacta in the brain with an unknown cause. Current pharmacological treatments for PD are only symptomatic and there is still no cure for this disease nowadays. In fact, transplantation of human fetal ventral midbrain cells into PD brains has provided a proof of concept that cell replacement therapy can be used for some PD patients, beneficial for improving their symptoms. However, the ethical and practical issues of human fetal tissue will inevitably limit its widespread clinical use. Therefore, it is essential to find alternative cell sources for the future cell transplantation for PD patients. With recent development in stem cell technology, here, we review the different types of stem cells and their main properties currently explored, which could be developed as a possible cell therapy for PD treatment. PMID- 26824871 TI - Arabinoxylan from Mucilage of Tomatoes (Solanum lycopersicum L.): Structure and Antinociceptive Effect in Mouse Models. AB - Tomato is a known functional food due to its content of bioactive compounds. Herein, polysaccharides were extracted from mucilage of tomatoes, and a purified fraction (PTOK) was analyzed by sugar composition, methylation, and NMR spectroscopy analysis. The results showed the presence of an arabinoxylan, having (1->4)-linked beta-d-Xylp units in the main chain, which carried a low proportion of branching (~5.6%), at O-2 and O-3 position, with side chains constituted by single Araf or Xylp units. Intraperitoneal administration of the arabinoxylan in mice significantly reduced the number of abdominal constrictions induced by 0.6% acetic acid and the inflammatory phase of nociception induced by 2.5% formalin, indicating that it had an antinociceptive effect on inflammatory pain models, amplifying the biological role displayed by arabinoxylans in the diet. Furthermore, this study reports the presence of an arabinoxylan in a dicotyledon plant, and also it is the first study of polysaccharides from mucilage of tomatoes. PMID- 26824872 TI - Formation of malondialdehyde (MDA), 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2 nonenal (HNE) in fish and fish oil during dynamic gastrointestinal in vitro digestion. AB - Marine lipids contain a high proportion of polyunsaturated fatty acids (PUFA), including the characteristic long chain (LC) n-3 PUFA. Upon peroxidation these lipids generate reactive products, such as malondialdehyde (MDA), 4-hydroxy-2 hexenal (HHE) and 4-hydroxy-2-nonenal (HNE), which can form covalent adducts with biomolecules and thus are regarded as genotoxic and cytotoxic. PUFA peroxidation can occur both before and after ingestion. The aim of this study was to determine what levels of MDA, HHE and HNE can evolve in the gastric and intestinal lumen after ingesting meals containing fish or fish oil using a dynamic gastrointestinal (GI) model (TIM). The impact of the fish muscle matrix, lipid content, fish species, and oven baking on GI oxidation was evaluated. MDA and HHE concentrations in gastric lumen increased for all meals during digestion, with the highest level found with herring mince; ~ 25 MUM MDA and ~ 850 nM HHE. Aldehyde concentrations reached in intestinal lumen during digestion of fish containing meals were generally lower than in gastric lumen, while isolated herring oils (bulk and emulsified) generated higher MDA and HHE values in intestinal lumen compared to gastric lumen. Based on aldehyde levels in gastric lumen, meals containing herring lipids were ranked: raw herring (17% lipid) = baked herring (4% lipid) > raw herring (4% lipid) ? herring oil emulsion > herring oil. Herring developed higher concentrations of MDA and HHE during gastric digestion compared to salmon, which initially contained lower levels of oxidation products. Cooked salmon generated higher MDA concentrations during digestion than raw salmon. Low levels of HNE were observed during digestion of all test meals, in accordance with the low content of n-6 PUFA in fish lipids. PMID- 26824873 TI - The Evolution of Pressurized Metered-Dose Inhalers from Early to Modern Devices. AB - Pressurized metered-dose inhalers (pMDIs) are sometimes viewed as old-fashioned and as having been superseded by dry powder inhalers (DPIs). Here, we review the technological advances that characterize modern pMDIs, and consider how they can influence the effectiveness of drug delivery for patients with asthma and chronic obstructive pulmonary disease. Compared with old chlorofluorocarbon (CFC)-based inhalers, many hydrofluoroalkane (HFA)-driven pMDIs have more favorable plume characteristics such as a reduced velocity and a higher fine particle fraction; together, these advances have resulted in the development of pMDIs with reduced oropharyngeal deposition and increased lung deposition. In addition, the plume from many HFA-pMDIs is warmer, which may facilitate their use by patients; moreover, devices are equipped with dose counters, which improves their reliability. As well as reviewing the technological advances of pMDIs, we also discuss the importance of individualizing inhaler therapies to each patient by accounting for their personal preferences and natural breathing patterns. Because pMDIs and DPIs differ considerably in their handling characteristics, matching the right inhaler to the right patient is key to ensuring effective therapy and good compliance. Finally, the majority of patients can be trained successfully in the correct use of their pMDI; training and regular monitoring of inhalation technique are essential prerequisites for effective therapy. While the 'ideal inhaler' may not exist, pMDIs are an effective device option suitable for many patients. pMDIs, together with other types of devices, offer opportunities for the effective individualization of treatments. PMID- 26824874 TI - Nitrogen removal by Providencia rettgeri strain YL with heterotrophic nitrification and aerobic denitrification. AB - Providencia rettgeri strain YL shows the capability of nitrogen removal under sole aerobic conditions. By using isotope ratio mass spectrometry, (15)N-labelled N2O and N2 were detected in aerobic batch cultures containing [Formula: see text], [Formula: see text] or [Formula: see text]. Strain YL converted [Formula: see text], [Formula: see text] and [Formula: see text] to produce more N2O than N2 in the presence of [Formula: see text]. An (15)N isotope tracing experiment confirmed that the nitrogen removal pathway of strain YL was heterotrophic nitrification-aerobic denitrification. The optimal treatment conditions for nitrogen removal were pH of 8, C/N ratio of 12, temperature of 25 degrees C and shaking speed of 105 rpm. A continuous aerobic bioreactor inoculated with strain YL was developed. With an influent [Formula: see text] concentration of 90-200 mg/L, the [Formula: see text] removal efficiency ranged from 80% to 97% and the total nitrogen removal efficiency ranged from 72% to 95%. The nitrogen balance in the continuous bioreactor revealed that approximately 35-52% of influent [Formula: see text] was denitrified aerobically to form gaseous nitrogen. These findings show that the P. rettgeri strain YL has potential application in wastewater treatment for nitrogen removal under sole aerobic conditions. PMID- 26824876 TI - Enhanced Patency and Endothelialization of Small-Caliber Vascular Grafts Fabricated by Coimmobilization of Heparin and Cell-Adhesive Peptides. AB - The clinical utility of a small-caliber vascular graft is still limited, owing to the occlusion of graft by thrombosis and restenosis. A small-caliber vascular graft (diameter, 2.5 mm) fabricated by electrospinning with a polyurethane (PU) elastomer (Pellethane) and biofunctionalized with heparin and two cell-adhesive peptides, GRGDS and YIGSR, was developed for the purpose of preventing the thrombosis and restenosis through antithrombogenic activities and endothelialization. The vascular grafts showed slightly reduced adhesion of platelets and significantly decreased adsorption of fibrinogen. In vitro studies demonstrated that peptide treatment on a vascular graft enhanced the attachment of human umbilical vein endothelial cells (HUVECs), and the presence of heparin and peptides on the graft significantly increased the proliferation of HUVECs. In vivo implantation of heparin/peptides coimmobilized graft (PU-PEG-Hep/G+Y) and PU (control) grafts was performed using an abdominal aorta rabbit model for 60 days followed by angiographic monitoring and explanting for histological analyses. The patency was significantly higher for the modified PU grafts (71.4%) compared to the PU grafts (46.2%) at 9 weeks after implantation. The nontreated PU grafts showed higher levels of alpha-SMA expression compared to the modified grafts, and for both samples, the proximal and distal regions expressed higher levels compared to the middle region of the grafts. Moreover, immobilization of heparin and peptides and adequate porous structure were found to play important roles in endothelialization and cellular infiltration. Our results strongly encourage that the development of small-caliber vascular grafts is feasible. PMID- 26824877 TI - Involvement of nitrogen functional groups in high-affinity copper binding in tomato and wheat root apoplasts: spectroscopic and thermodynamic evidence. AB - Carboxylic groups located in plant cell walls (CW) are generally considered to be the main copper binding sites in plant roots, despite the presence of other functional groups. The aim of this study was to investigate sites responsible for copper binding in root apoplasts, i.e. CW and outer surface of the plasma membrane (PM) continuum. Binding sites in root apoplasts were investigated by comparing isolated CW of a monocotyledon (Triticum aestivum L.) and dicotyledon (Solanum lycopersicum L.) crop with their respective whole roots. Copper speciation was examined by X-ray absorption (XAS) and (13)C-nuclear magnetic resonance spectroscopies while the affinity of ligands involved in copper binding was investigated by modeling copper sorption isotherms. Homogeneous speciation and binding of copper was found in wheat and tomato root apoplasts. Only Cu-N and Cu-O bonds were detected in wheat and tomato root apoplasts. Nitrogen/oxygen ligands were identified in slightly higher proportions (40-70%) than single oxygen ligands. Furthermore, low- and high-affinity binding sites contributed in an almost equivalent proportion to copper binding in root apoplasts. The high affinity N functional groups embedded in root apoplasts participated in copper binding in the same magnitude than the low-affinity carboxylic groups. PMID- 26824878 TI - Efficient Electrochemical Water Splitting Catalyzed by Electrodeposited Nickel Diselenide Nanoparticles Based Film. AB - In this contribution, we demonstrate that electrodeposited nickel diselenide nanoparticles based film on conductive Ti plate (NiSe2/Ti) is an efficient and robust electrode to catalyze both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in basic media. Electrochemical experiments show this electrode affords 10 mA cm(-2) at HER overpotential of 96 mV and 20 mA cm(-2) at OER overpotential of 295 mV with strong durability in 1.0 M KOH. The corresponding two-electrode alkaline water electrolyzer requires a cell voltage of only 1.66 V to achieve 10 mA cm(-2) water-splitting current. This development provides us an attractive non-noble-metal catalyst toward overall water splitting applications. PMID- 26824875 TI - Spontaneous Ca(2+) transients in interstitial cells of Cajal located within the deep muscular plexus of the murine small intestine. AB - KEY POINTS: Interstitial cells of Cajal at the level of the deep muscular plexus (ICC-DMP) in the small intestine generate spontaneous Ca(2+) transients that consist of localized Ca(2+) events and limited propagating Ca(2+) waves. Ca(2+) transients in ICC-DMP display variable characteristics: from discrete, highly localized Ca(2+) transients to regionalized Ca(2+) waves with variable rates of occurrence, amplitude, duration and spatial spread. Ca(2+) transients fired stochastically, with no cellular or multicellular rhythmic activity being observed. No correlation was found between the firing sites in adjacent cells. Ca(2+) transients in ICC-DMP are suppressed by the ongoing release of inhibitory neurotransmitter(s). Functional intracellular Ca(2+) stores are essential for spontaneous Ca(2+) transients, and the sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) pump is necessary for maintenance of spontaneity. Ca(2+) release mechanisms involve both ryanodine receptors (RyRs) and inositol triphosphate receptors (InsP3 Rs). Release from these channels is interdependent. ICC express transcripts of multiple RyRs and InsP3 Rs, with Itpr1 and Ryr2 subtypes displaying the highest expression. ABSTRACT: Interstitial cells of Cajal in the deep muscular plexus of the small intestine (ICC-DMP) are closely associated with varicosities of enteric motor neurons and generate responses contributing to neural regulation of intestinal motility. Responses of ICC-DMP are mediated by activation of Ca(2+) -activated Cl(-) channels; thus, Ca(2+) signalling is central to the behaviours of these cells. Confocal imaging was used to characterize the nature and mechanisms of Ca(2+) transients in ICC-DMP within intact jejunal muscles expressing a genetically encoded Ca(2+) indicator (GCaMP3) selectively in ICC. ICC-DMP displayed spontaneous Ca(2+) transients that ranged from discrete, localized events to waves that propagated over variable distances. The occurrence of Ca(2+) transients was highly variable, and it was determined that firing was stochastic in nature. Ca(2+) transients were tabulated in multiple cells within fields of view, and no correlation was found between the events in adjacent cells. TTX (1 MUm) significantly increased the occurrence of Ca(2+) transients, suggesting that ICC-DMP contributes to the tonic inhibition conveyed by ongoing activity of inhibitory motor neurons. Ca(2+) transients were minimally affected after 12 min in Ca(2+) free solution, indicating these events do not depend immediately upon Ca(2+) influx. However, inhibitors of sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) pump and blockers of inositol triphosphate receptor (InsP3 R) and ryanodine receptor (RyR) channels blocked ICC Ca(2+) transients. These data suggest an interdependence between RyR and InsP3 R in the generation of Ca(2+) transients. Itpr1 and Ryr2 were the dominant transcripts expressed by ICC. These findings provide the first high-resolution recording of the subcellular Ca(2+) dynamics that control the behaviour of ICC DMP in situ. PMID- 26824879 TI - Biophysical properties of dermal building-blocks affects extra cellular matrix assembly in 3D endogenous macrotissue. AB - The fabrication of functional tissue units is one of the major challenges in tissue engineering due to their in vitro use in tissue-on-chip systems, as well as in modular tissue engineering for the construction of macrotissue analogs. In this work, we aim to engineer dermal tissue micromodules obtained by culturing human dermal fibroblasts into porous gelatine microscaffold. We proved that such stromal cells coupled with gelatine microscaffolds are able to synthesize and to assemble an endogenous extracellular matrix (ECM) resulting in tissue micromodules, which evolve their biophysical features over the time. In particular, we found a time-dependent variation of oxygen consumption kinetic parameters, of newly formed ECM stiffness and of micromodules self-aggregation properties. As consequence when used as building blocks to fabricate larger tissues, the initial tissue micromodules state strongly affects the ECM organization and maturation in the final macrotissue. Such results highlight the role of the micromodules properties in controlling the formation of three dimensional macrotissue in vitro, defining an innovative design criterion for selecting tissue-building blocks for modular tissue engineering. PMID- 26824880 TI - Maximum Entropy-Based Ecological Niche Model and Bio-Climatic Determinants of Lone Star Tick (Amblyomma americanum) Niche. AB - The potential distribution of Amblyomma americanum ticks in Kansas was modeled using maximum entropy (MaxEnt) approaches based on museum and field-collected species occurrence data. Various bioclimatic variables were used in the model as potentially influential factors affecting the A. americanum niche. Following reduction of dimensionality among predictor variables using principal components analysis, which revealed that the first two principal axes explain over 87% of the variance, the model indicated that suitable conditions for this medically important tick species cover a larger area in Kansas than currently believed. Soil moisture, temperature, and precipitation were highly correlated with the first two principal components and were influential factors in the A. americanum ecological niche. Assuming that the niche estimated in this study covers the occupied distribution, which needs to be further confirmed by systematic surveys, human exposure to this known disease vector may be considerably under-appreciated in the state. PMID- 26824881 TI - Intracerebroventricular delivery of self-complementary adeno-associated virus serotype 9 to the adult rat brain. AB - Gene therapy for the central nervous system is poised to become a powerful treatment for numerous neurological disorders. Adeno-associated viral vectors based on serotype 9 (AAV9) have proven themselves to be strong candidates for delivering gene-based therapies throughout the brain and spinal cord when administered intravenously, intrathecally, intracisternally, and intracerebroventricularly (i.c.v.). Previous studies of i.c.v.-delivered self complimentary AAV9 have been performed in neonatal mice with delivery of a single dose. However, before clinical trials can be considered, more information is required about the dose-response relationship for transduction efficiency in adult animals. In the current study, three doses of self-complementary AAV9 were administered to adult rats. High levels of transduction were observed in the hippocampus, cerebellum and cerebral cortex, and transduction increased with increasing dosage. Both neurons and astrocytes were transduced. There was no evidence of astrocytosis at the doses tested. Preliminary results from pigs receiving i.c.v. self-complementary AAV9 are also presented. The results of this study will serve to inform dosing studies in large animal models before clinical testing. PMID- 26824882 TI - HIV is not transmitted under fully suppressive therapy: The Swiss Statement- eight years later. PMID- 26824883 TI - Tensor-based classification of an auditory mobile BCI without a subject-specific calibration phase. AB - OBJECTIVE: One of the major drawbacks in EEG brain-computer interfaces (BCI) is the need for subject-specific training of the classifier. By removing the need for a supervised calibration phase, new users could potentially explore a BCI faster. In this work we aim to remove this subject-specific calibration phase and allow direct classification. APPROACH: We explore canonical polyadic decompositions and block term decompositions of the EEG. These methods exploit structure in higher dimensional data arrays called tensors. The BCI tensors are constructed by concatenating ERP templates from other subjects to a target and non-target trial and the inherent structure guides a decomposition that allows accurate classification. We illustrate the new method on data from a three-class auditory oddball paradigm. MAIN RESULTS: The presented approach leads to a fast and intuitive classification with accuracies competitive with a supervised and cross-validated LDA approach. SIGNIFICANCE: The described methods are a promising new way of classifying BCI data with a forthright link to the original P300 ERP signal over the conventional and widely used supervised approaches. PMID- 26824884 TI - Efficacy of a new once daily hydromorphone formulation in comparison with twice daily administration in chronic pain: a randomized, double-blind, cross-over study. AB - Objective Efficacy and safety of a novel multiple-unit hydromorphone once daily (HOD) was compared to an established hydromorphone twice daily (HTD) regimen in patients with moderate-to-severe chronic pain. Design and methods The results from a randomized, double-blind, multicenter, cross-over trial in patients (n = 37) with chronic malignant or non-malignant pain are reported. The primary efficacy parameter was current pain on 0-100 mm VAS assessed four times daily and prior to intake of rescue medication (immediate-release hydromorphone) throughout the last 5 days with each treatment (after an 8 day build-up period to avoid carry-over effects). Total daily dose of hydromorphone (TDD: 8-32 mg/day) was kept stable during the double-blind treatment phase. Results The difference observed in mean current pain (-0.92 mm VAS) over the 5 day assessment period between HOD and HTD (28.44 mm vs. 29.36 mm VAS) was found to lack clinical relevance, as the 95% CI (-4.10 to 2.28 mm VAS) did not exceed the prespecified limit for non-inferiority of 9 mm VAS. Results from the full analysis set were consistent with per protocol data confirming robustness, as did the data for 12 h recalled pain assessed at 08:00 h and 20:00 h, showing no significant differences between once and twice daily medication. Both treatments produced effective and stable pain control with only minor day-to-day and intra-day fluctuations. Switching between treatments was suitable, considering both efficacy and safety, as no relevant or significant differences in adverse events were seen (25.0% HOD, 24.3% HTD). Most frequently typical side-effects of opioid therapy were observed, such as nausea, vomiting and headache. Conclusion Although this study was of short duration and included a limited number of patients, the results confirm that the new HOD is as effective and safe as the established HTD. PMID- 26824885 TI - Retention procedures for stabilising tooth position after treatment with orthodontic braces. AB - BACKGROUND: Retention is the phase of orthodontic treatment that attempts to keep teeth in the corrected positions after treatment with orthodontic braces. Without a phase of retention, there is a tendency for teeth to return to their initial position (relapse). To prevent relapse, almost every person who has orthodontic treatment will require some type of retention. OBJECTIVES: To evaluate the effects of different retention strategies used to stabilise tooth position after orthodontic braces. SEARCH METHODS: We searched the following databases: the Cochrane Oral Health Group's Trials Register (to 26 January 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 12), MEDLINE via Ovid (1946 to 26 January 2016) and EMBASE via Ovid (1980 to 26 January 2016). We searched for ongoing trials in the US National Institutes of Health Trials Register (ClinicalTrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform. We applied no language or date restrictions in the searches of the electronic databases. We contacted authors of randomised controlled trials (RCTs) to help identify any unpublished trials. SELECTION CRITERIA: RCTs involving children and adults who had had retainers fitted or adjunctive procedures undertaken to prevent relapse following orthodontic treatment with braces. DATA COLLECTION AND ANALYSIS: Two review authors independently screened eligible studies, assessed the risk of bias in the trials and extracted data. The outcomes of interest were: how well the teeth were stabilised, failure of retainers, adverse effects on oral health and participant satisfaction. We calculated mean differences (MD) with 95% confidence intervals (CI) for continuous data and risk ratios (RR) with 95% CI for dichotomous outcomes. We conducted meta-analyses when studies with similar methodology reported the same outcome. We prioritised reporting of Little's Irregularity Index to measure relapse. MAIN RESULTS: We included 15 studies (1722 participants) in the review. There are also four ongoing studies and four studies await classification. The 15 included studies evaluated four comparisons: removable retainers versus fixed retainers (three studies); different types of fixed retainers (four studies); different types of removable retainers (eight studies); and one study compared a combination of upper thermoplastic and lower bonded versus upper thermoplastic with lower adjunctive procedures versus positioner. Four studies had a low risk of bias, four studies had an unclear risk of bias and seven studies had a high risk of bias. Removable versus fixed retainers Thermoplastic removable retainers provided slightly poorer stability in the lower arch than multistrand fixed retainers: MD (Little's Irregularity Index, 0 mm is stable) 0.6 mm (95% CI 0.17 to 1.03). This was based on one trial with 84 participants that was at high risk of bias; it was low quality evidence. Results on retainer failure were inconsistent. There was evidence of less gingival bleeding with removable retainers: RR 0.53 (95% CI 0.31 to 0.88; one trial, 84 participants, high risk of bias, low quality evidence), but participants found fixed retainers more acceptable to wear, with a mean difference on a visual analogue scale (VAS; 0 to 100; 100 being very satisfied) of -12.84 (95% CI -7.09 to -18.60). Fixed versus fixed retainersThe studies did not report stability, adverse effects or participant satisfaction. It was possible to pool the data on retention failure from three trials that compared polyethylene ribbon bonded retainer versus multistrand retainer in the lower arch with an RR of 1.10 (95% CI 0.77 to 1.57; moderate heterogeneity; three trials, 228 participants, low quality evidence). There was no evidence of a difference in failure rates. It was also possible to pool the data from two trials that compared the same types of upper fixed retainers, with a similar finding: RR 1.25 (95% CI 0.87 to 1.78; low heterogeneity; two trials, 174 participants, low quality evidence). Removable versus removable retainersOne study at low risk of bias comparing upper and lower part-time thermoplastic versus full-time thermoplastic retainer showed no evidence of a difference in relapse (graded moderate quality evidence). Another study, comparing part-time and full-time wear of lower Hawley retainers, found no evidence of any difference in relapse (low quality evidence). Two studies at high risk of bias suggested that stability was better in the lower arch for thermoplastic retainers versus Hawley, and for thermoplastic full-time versus Begg (full-time) (both low quality evidence).In one study, participants wearing Hawley retainers reported more embarrassment more often than participants wearing thermoplastic retainers: RR 2.42 (95% CI 1.30 to 4.49; one trial, 348 participants, high risk of bias, low quality evidence). They also found Hawley retainers harder to wear. There was conflicting evidence about survival rates of Hawley and thermoplastic retainers. Other retainer comparisonsAnother study with a low risk of bias looked at three different approaches to retention for people with crowding, but normal jaw relationships. The study found that there was no evidence of a difference in relapse between the combination of an upper thermoplastic and lower canine to canine bonded retainer and the combination of an upper thermoplastic retainer and lower interproximal stripping, without a lower retainer. Both these approaches are better than using a positioner as a retainer. AUTHORS' CONCLUSIONS: We did not find any evidence that wearing thermoplastic retainers full-time provides greater stability than wearing them part-time, but this was assessed in only a small number of participants.Overall, there is insufficient high quality evidence to make recommendations on retention procedures for stabilising tooth position after treatment with orthodontic braces. Further high quality RCTs are needed. PMID- 26824886 TI - An external focus of attention is a conditio sine qua non for athletes: a response to Carson, Collins, and Toner (2015). AB - In this invited response to a Letter to the Editor by Carson, Collins, and Toner (2015), I comment on various issues raised by the authors. I highlight the broad range of tasks and dependent measures used in studies comparing the effectiveness of external versus internal foci of attention. These studies--many of which involved sport skills--have consistently found performance or learning benefits when an external focus was adopted. There is no convincing evidence that performers' preferences, or their familiarity with a certain focus, have a moderating effect. Anecdotal evidence reported by coaches who have compared the two types of foci is consistent with research findings. An external focus presumably promotes functional connectivity and contributes to goal-action coupling. PMID- 26824887 TI - Foxc1 Regulates Early Cardiomyogenesis and Functional Properties of Embryonic Stem Cell Derived Cardiomyocytes. AB - Embryonic Stem Cells (ESCs) hold great potential for regeneration of damaged myocardium, however the molecular circuitry that guides ESC differentiation into cardiomyocytes remains poorly understood. This is exemplified by the elusive role of the transcription factor, Foxc1, during cardiac development. The only known Foxc1 target during heart development is Tbx1. Because Foxc1 null mice contain heart mutations that are far more severe than Tbx1 null mice, it is likely that Foxc1 has additional regulatory roles during heart development. The goal of our study was to test whether Foxc1 is critical for ESC differentiation into functional cardiomyocytes through proper regulation of specific downstream gene networks. Converging evidence from Foxc1 deficient and overexpression ESC models reveals a close relationship between Foxc1 levels and early cardiomyogenic factors Isl1, Mef2c, and Nkx2.5 and also the production of functional cardiomyocytes. We show Foxc1 regulates early cardiomyogenesis during a specific window of differentiation, D4-D6. Through whole transcriptome RNA-sequencing analysis, we report pathways regulated by Foxc1 involved in cardiac function including actin cytoskeleton, cell adhesion, tight and gap junctions, and calcium signaling. Our data indicate a novel Foxc1 direct gene target, Myh7, which encodes the predominant myosin heavy chain isoform, MHCbeta, expressed during cardiac development. These data lead us to conclude that Foxc1 regulates both early cardiomyogenesis and the functional properties of ESC-derived cardiomyocytes. Our findings shed light on the molecular circuitry governing cardiomyogenesis that may lead to the development of better translational strategies for the use of pluripotent stem cells in regenerative medicine towards repairing damaged myocardium. Stem Cells 2016;34:1487-1500. PMID- 26824888 TI - Social cohesion, social participation and HIV testing among men who have sex with men in Swaziland. AB - Social cohesion and social participation are social factors that may help reduce HIV risks and optimize health-seeking behaviors. We examined the association between these factors and HIV testing in the last 12 months among men who have sex with men (MSM) in Swaziland using a cross-sectional survey conducted with 326 men, 18 years of age or older reporting having sex with another man in the last 12 months. Social capital analyses included measures of social cohesion and social participation. The social cohesion measurement scale was created through exploratory factor analysis using polychoric correlations to determine unidimensionality and Cronbach's Alpha to assess internal consistency. The measurement scale was divided at the 25th and 75th percentiles using "high," "medium" and "low" levels of social cohesion for between-group comparisons. The social participation index included four questions regarding participation, resulting in a participation index ranging from 0 to 4. In the final multivariate logistic regression model, an increase in the level of social participation was found to be significantly associated with HIV testing in the last 12 months, adjusting for age, income, reporting a casual partner, family exclusion and rejection by other MSM due to sexual orientation (adjusted odds ratio [aOR]: 1.3, 95% confidence interval [CI] 1.1-1.7, p < .01). MSM with high social cohesion had almost twice the odds of HIV testing in the last 12 months (aOR: 1.8, 95% CI 1.1 3.3, p < .05) as MSM with medium social cohesion, though the overall social cohesion variable was not found to be significant using a Wald test in either the adjusted or unadjusted logistic regression models. These data suggest that building solidarity and trust within and between groups may be a strategy to improve uptake of HIV testing. PMID- 26824889 TI - Bacterial composition in whole saliva from patients with severe hyposalivation--a case-control study. AB - OBJECTIVE: The purpose of this study was to compare the microbiota of stimulated whole saliva samples from patients with severe hyposalivation to samples from individuals with normal whole saliva flow rates. It was hypothesized that the two groups differ with regard to salivary bacterial profiles. METHODS: This cross sectional study included 36 participants (24 females and 12 males, mean age 58.5 years) with severe hyposalivation and 36 gender-, age-, and geographically matched participants with normal salivary secretion from the Danish Health Examination Survey (DANHES). The microbiota of stimulated whole saliva samples was characterized by HOMINGS. RESULTS: The two groups had comparable caries experience measured by decayed, missed, filled surfaces/teeth and decayed, missed, filled root surfaces as well as active caries lesions. In addition, no single probe target was present with a significant difference in frequency or proportional presence between groups. Furthermore, data reduction by principal component analysis and correspondence analysis showed comparable bacterial community profiles between groups. CONCLUSIONS: The results indicate that the salivary bacterial profiles of patients with severe hyposalivation do not differ from those of individuals with normal salivary secretion, when there are virtually no untreated active caries lesions present in the oral cavity. PMID- 26824890 TI - Nursing Practice Guidelines in China do Need Reform: A Critical Appraisal Using the AGREE II Instrument. AB - BACKGROUND: An increasing number of nursing practice guidelines (NPGs) of varying methodological and reporting quality have been issued and published in international journals. Currently, the quality of NPGs in mainland China has not been explored. OBJECTIVE: To assess the quality of NPGs in China mainland using the AGREE II (Advancing Guideline Development, Reporting and Evaluation in Health Care) instrument. METHODS: The authors searched the electronic databases of Chinese Biomedical Literature Database, China National Knowledge Infrastructure, The VIP Database, Wan Fang Database, Chinese Master's Theses Full-Text Database, China Doctor Dissertation Full-Text Database, and China Proceedings of Conference Full-Text Database and the web of China Guideline Clearinghouse for NPGs in China published from the inception of databases to December, 2013. Four independent assessors rated the quality of each guideline using AGREE II. The authors classified NPGs into two types: evidence-based NPG (EB-NPG) and consensus-based NPG (CB-NPG), and compared their quality. The authors also considered whether the quality of NPGs changed over time. RESULTS: Forty-two NPGs were appraised. Methodological rigor and reporting of NPGs were poor. Across all guidelines, the appraisers assigned the highest scores to the domain "scope and purpose," and the lowest scored to the domain of "editorial independence." EB-NPGs were significantly superior to the CB-NPGs in the domains of "stakeholder involvement," "rigor of development," and "editorial independence." There was no improvement over time for all domains. LINKING EVIDENCE TO ACTION: This research found an absence of a systematic guideline development methodology and a tendency to rely on expert opinion in the process of developing NPGs. The readers should consider these flaws and limitations when using recommendations in those NPGs. PMID- 26824891 TI - Tobacco advertising, promotion, and sponsorship (TAPS) exposure, anti-TAPS policies, and students' smoking behavior in Botswana and South Africa. AB - OBJECTIVE: We examined the change over time in tobacco advertising, promotion and sponsorship exposure and the concurrent changes in cigarette smoking behavior among students age 13 to 15years in two African countries with different anti tobacco advertising, promotion and sponsorship policies. In South Africa, anti tobacco advertising, promotion and sponsorship policies became more comprehensive over time and were more strictly enforced, whereas the partial anti-tobacco advertising, promotion and sponsorship policies adopted in Botswana were weakly enforced. METHOD: We analyzed two rounds of Global Youth Tobacco Survey data from South Africa (1999, n=2342; 2011, n=3713) and in Botswana (2001, n=1073; 2008, n=1605). We assessed several indicators of tobacco advertising, promotion and sponsorship exposure along with prevalence of current cigarette smoking and smoking susceptibility for each data round. Logistic regression was used to examine changes over time in tobacco advertising, promotion and sponsorship exposure and smoking behavior in both countries. RESULTS: Between 1999 and 2011, South African students' exposure to tobacco advertising and sponsorship decreased significantly by 16% (p value, <0.0001) and 14% (p value, <0.0001), respectively. Exposure to tobacco promotion was lower and did not decrease significantly. Botswanan students' tobacco advertising, promotion and sponsorship exposure did not change significantly between 2001 and 2008. South African students' prevalence of cigarette smoking decreased over time (OR, 0.68) as did susceptibility to smoking (OR, 0.75), but declines did not remain significant after adjusting for parents' and friends' smoking. In Botswana, students' prevalence of cigarette smoking increased significantly over time (OR, 1.84), as did susceptibility to smoking (OR, 2.71). CONCLUSION: Enforcement of strong anti tobacco advertising, promotion and sponsorship policies is a vital component of effective tobacco control programs in Africa. Such regulations, if effectively implemented, can reduce tobacco advertising, promotion and sponsorship exposure among adolescents and may influence cigarette smoking behavior. PMID- 26824893 TI - Beta-Cell Replacement: Pancreas and Islet Cell Transplantation. AB - Pancreas and islet transplantation are 2 types of beta-cell replacement therapies for type 1 diabetes mellitus. Since 1966, when pancreas transplantation was first performed, it has evolved to become a highly efficient procedure with high success rates, thanks to advances in surgical technique and immunosuppression. Pancreas transplantation is mostly performed as simultaneous pancreas-kidney transplantation in patients with end-stage nephropathy secondary to diabetes. In spite of its efficiency, pancreas transplantation is still a major surgical procedure burdened by high morbidity, which called for the development of less invasive and hazardous ways of replacing beta-cell function in the past. Islet transplantation was developed in the 1970s as a minimally invasive procedure with initially poor outcomes. However, since the report of the 'Edmonton protocol' in 2000, the functional results of islet transplantation have substantially and constantly improved and are about to match those of whole pancreas transplantation. Islet transplantation is primarily performed alone in nonuremic patients with severe hypoglycemia. Both pancreas transplantation and islet transplantation are able to abolish hypoglycemia and to prevent or slow down the development of secondary complications of diabetes. Pancreas transplantation and islet transplantation should be seen as two complementary, rather than competing, therapeutic approaches for beta-cell replacement that are able to optimize organ donor use and patient care. PMID- 26824892 TI - Receptor for Advanced Glycation End Products (RAGE) Serves a Protective Role during Klebsiella pneumoniae - Induced Pneumonia. AB - Klebsiella species is the second most commonly isolated gram-negative organism in sepsis and a frequent causative pathogen in pneumonia. The receptor for advanced glycation end products (RAGE) is expressed on different cell types and plays a key role in diverse inflammatory responses. We here aimed to investigate the role of RAGE in the host response to Klebsiella (K.) pneumoniae pneumonia and intransally inoculated rage gene deficient (RAGE-/-) and normal wild-type (Wt) mice with K. pneumoniae. Klebsiella pneumonia resulted in an increased pulmonary expression of RAGE. Furthermore, the high-affinity RAGE ligand high mobility group box-1 was upregulated during K. pneumoniae pneumonia. RAGE deficiency impaired host defense as reflected by a worsened survival, increased bacterial outgrowth and dissemination in RAGE-/- mice. RAGE-/- neutrophils showed a diminished phagocytosing capacity of live K. pneumoniae in vitro. Relative to Wt mice, RAGE-/- mice demonstrated similar lung inflammation, and slightly elevated if any-cytokine and chemokine levels and unchanged hepatocellular injury. In addition, RAGE-/- mice displayed an unaltered response to intranasally instilled Klebsiella lipopolysaccharide (LPS) with respect to pulmonary cell recruitment and local release of cytokines and chemokines. These data suggest that (endogenous) RAGE protects against K. pneumoniae pneumonia. Also, they demonstrate that RAGE contributes to an effective antibacterial defense during K. pneumoniae pneumonia, at least partly via its participation in the phagocytic properties of professional granulocytes. Additionally, our results indicate that RAGE is not essential for the induction of a local and systemic inflammatory response to either intact Klebsiella or Klebsiella LPS. PMID- 26824894 TI - Biomarkers. PMID- 26824895 TI - Deception Undermines the Stability of Cooperation in Games of Indirect Reciprocity. AB - Indirect reciprocity is often claimed as one of the key mechanisms of human cooperation. It works only if there is a reputational score keeping and each individual can inform with high probability which other individuals were good or bad in the previous round. Gossip is often proposed as a mechanism that can maintain such coherence of reputations in the face of errors of transmission. Random errors, however, are not the only source of uncertainty in such situations. The possibility of deceptive communication, where the signallers aim to misinform the receiver cannot be excluded. While there is plenty of evidence for deceptive communication in humans the possibility of deception is not yet incorporated into models of indirect reciprocity. Here we show that when deceptive strategies are allowed in the population it will cause the collapse of the coherence of reputations and thus in turn it results the collapse of cooperation. This collapse is independent of the norms and the cost and benefit values. It is due to the fact that there is no selection for honest communication in the framework of indirect reciprocity. It follows that indirect reciprocity can be only proposed plausibly as a mechanism of human cooperation if additional mechanisms are specified in the model that maintains honesty. PMID- 26824896 TI - Histatin-1 Expression in Human Lacrimal Epithelium. AB - BACKGROUND: Study of human lacrimal cell biology is limited by poor access to tissue samples, heterogeneous cell composition of tissue and a lack of established lacrimal epithelial markers. In order to further our understanding of lacrimal cell biology, we sought to find a better marker for human lacrimal epithelial cells, compared to what has been reported in the literature. METHODS: We utilized human Muller's muscle conjunctival resection (MMCR) specimens containing accessory lacrimal gland (ALG) and cadaveric main lacrimal gland (MLG) as sources of lacrimal tissue. Candidate markers were sought using human ALG tissue from MMCR specimens, isolated by laser capture microdissection (LCM). Affymetrix(r) analysis was performed on total RNA isolated from FFPE samples to profile transcription in ALG. MMCR tissue sections were assessed by immunofluorescence using antibodies for histatin-1, lactoferrin, E-cadherin (E cad) and alpha-smooth muscle actin (ASMA). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis was performed to analyze the expression of histatin-1, E-cad and lactoferrin from cadaveric MLG. RESULTS: Histatin-1 is expressed in ALG and MLG, localizes to lacrimal epithelium, and to a greater degree than do other putative lacrimal epithelial markers. CONCLUSIONS: Histatin-1 is a good marker for human lacrimal epithelium in ALG and MLG and can be used to identify lacrimal cells in future studies. PMID- 26824898 TI - MiR 21-5p as a predictor of recurrence in young gastric cancer patients. AB - BACKGROUND AND AIM: It is generally assumed that gastric cancer (GC) in young patients has different clinicopathologic characteristics than that of elderly patients. Although recurrence is an important factor in determining prognosis, traditional clinicopathological factors are sometimes inadequate for predicting recurrence in individuals. Therefore, we aimed to identify miRNAs with the potential to predict recurrence in young patients. METHODS: Young patients (age <40 years) undergoing gastrectomy for potentially curable GC (stage III) at Asan Medical Center participated in this study. A total of 50 GC patients with (n = 28) and without (n = 22) GC recurrence were selected for analysis. miRNA microarrays were analyzed to screen tissue samples (n = 7), and we validated the selected miRNAs by quantitative PCR in validation samples (n = 43). RESULTS: Two miRNAs (hsa-miR-21-5p and hsa-miR-451a) identified in the microarray analysis were evaluated in the validation samples. Among the validation samples containing intratumoral stroma >= 70 (n = 35), hsa-miR-21-5p was more highly expressed in the recurrence group than in the nonrecurrence group (fold change 1.82, P = 0.03). In the validation samples with intratumoral stroma >= 70, the DeltaCt of hsa-miR-21-5p, which was >3.35, had a sensitivity and specificity of 86.7% and 65.5%, respectively, for predicting recurrence, with an area under the ROC curve of 0.723. CONCLUSIONS: miR-21-5p may be useful as a predictor of recurrence in young GC patients whose tumors contain a high proportion of intratumoral stroma. The combination of this miRNA with conventional clinicopathological factors should allow patient prognoses to be more accurately predicted. PMID- 26824897 TI - A Novel High-Throughput Method for Molecular Detection of Human Pathogenic Viruses Using a Nanofluidic Real-Time PCR System. AB - Human enteric viruses are recognized as the main causes of food- and waterborne diseases worldwide. Sensitive and quantitative detection of human enteric viruses is typically achieved through quantitative RT-PCR (RT-qPCR). A nanofluidic real time PCR system was used to develop novel high-throughput methods for qualitative molecular detection (RT-qPCR array) and quantification of human pathogenic viruses by digital RT-PCR (RT-dPCR). The performance of high-throughput PCR methods was investigated for detecting 19 human pathogenic viruses and two main process controls used in food virology. The conventional real-time PCR system was compared to the RT-dPCR and RT-qPCR array. Based on the number of genome copies calculated by spectrophotometry, sensitivity was found to be slightly better with RT-qPCR than with RT-dPCR for 14 viruses by a factor range of from 0.3 to 1.6 log10. Conversely, sensitivity was better with RT-dPCR than with RT-qPCR for seven viruses by a factor range of from 0.10 to 1.40 log10. Interestingly, the number of genome copies determined by RT-dPCR was always from 1 to 2 log10 lower than the expected copy number calculated by RT-qPCR standard curve. The sensitivity of the RT-qPCR and RT-qPCR array assays was found to be similar for two viruses, and better with RT-qPCR than with RT-qPCR array for eighteen viruses by a factor range of from 0.7 to 3.0 log10. Conversely, sensitivity was only 0.30 log10 better with the RT-qPCR array than with conventional RT-qPCR assays for norovirus GIV detection. Finally, the RT-qPCR array and RT-dPCR assays were successfully used together to screen clinical samples and quantify pathogenic viruses. Additionally, this method made it possible to identify co-infection in clinical samples. In conclusion, given the rapidity and potential for large numbers of viral targets, this nanofluidic RT-qPCR assay should have a major impact on human pathogenic virus surveillance and outbreak investigations and is likely to be of benefit to public health. PMID- 26824899 TI - Glutamate Dehydrogenase Is Required by Mycobacterium bovis BCG for Resistance to Cellular Stress. AB - We recently reported on our success to generate deletion mutants of the genes encoding glutamate dehydrogenase (GDH) and glutamine oxoglutarate aminotransferase (GOGAT) in M. bovis BCG, despite their in vitro essentiality in M. tuberculosis. We could use these mutants to delineate the roles of GDH and GOGAT in mycobacterial nitrogen metabolism by using M. bovis BCG as a model for M. tuberculosis specifically. Here, we extended our investigation towards the involvement of GDH and GOGAT in other aspects of M. bovis BCG physiology, including the use of glutamate as a carbon source and resistance to known phagosomal stresses, as well as in survival inside macrophages. We find that gdh is indispensable for the utilization of glutamate as a major carbon source, in low pH environments and when challenged with nitric oxide. On the other hand, the gltBD mutant had increased viability under low pH conditions and was unaffected by a challenge with nitric oxide. Strikingly, GDH was required to sustain M. bovis BCG during infection of both murine RAW 264.7 and bone-marrow derived and macrophages, while GOGAT was not. We conclude that the catabolism of glutamate in slow growing mycobacteria may be a crucial function during infection of macrophage cells and demonstrate a novel requirement for M. bovis BCG GDH in the protection against acidic and nitrosative stress. These results provide strong clues on the role of GDH in intracellular survival of M. tuberculosis, in which the essentiality of the gdh gene complicates knock out studies making the study of the role of this enzyme in pathogenesis difficult. PMID- 26824900 TI - Classification of Asthma Based on Nonlinear Analysis of Breathing Pattern. AB - Normal human breathing exhibits complex variability in both respiratory rhythm and volume. Analyzing such nonlinear fluctuations may provide clinically relevant information in patients with complex illnesses such as asthma. We compared the cycle-by-cycle fluctuations of inter-breath interval (IBI) and lung volume (LV) among healthy volunteers and patients with various types of asthma. Continuous respiratory datasets were collected from forty age-matched men including 10 healthy volunteers, 10 patients with controlled atopic asthma, 10 patients with uncontrolled atopic asthma, and 10 patients with uncontrolled non-atopic asthma during 60 min spontaneous breathing. Complexity of breathing pattern was quantified by calculating detrended fluctuation analysis, largest Lyapunov exponents, sample entropy, and cross-sample entropy. The IBI as well as LV fluctuations showed decreased long-range correlation, increased regularity and reduced sensitivity to initial conditions in patients with asthma, particularly in uncontrolled state. Our results also showed a strong synchronization between the IBI and LV in patients with uncontrolled asthma. Receiver operating characteristic (ROC) curve analysis showed that nonlinear analysis of breathing pattern has a diagnostic value in asthma and can be used in differentiating uncontrolled from controlled and non-atopic from atopic asthma. We suggest that complexity analysis of breathing dynamics may represent a novel physiologic marker to facilitate diagnosis and management of patients with asthma. However, future studies are needed to increase the validity of the study and to improve these novel methods for better patient management. PMID- 26824901 TI - Factors Associated with Therapeutic Efficacy of Intravesical OnabotulinumtoxinA Injection for Overactive Bladder Syndrome. AB - OBJECTIVES: To analyze the predictors of therapeutic efficacy after intravesical botulinum toxin A injection for overactive bladder syndrome (OAB) refractory to antimuscarinic therapy. METHODS: All consecutively OAB patients, who visited the urologic outpatient clinics of a medical center and refractory to antimuscarinic treatment, were prospectively enrolled. All enrolled patients received intravesical injection of 100 U onabotulinumtoxinA (Botox). The Global Response Assessment (GRA) score >= 2 at 3 months after Botox injection was defined as a successful treatment, otherwise failed. RESULTS: Overall, 89 patients received intravesical injection. Eighty patients, including 42 men and 38 women, had received follow-up at 3 months. The overall success rate was 63.8%. The global response assessment, urgency severity score, urgency, urgency urinary incontinence and frequency episodes, and functional bladder capacity improved after treatment. However, post-void residual volume (PVR) increased, and voiding efficiency (VE) decreased after treatment. Female gender (odds ratio = 3.75) was the only independent factor associated with the success. Female gender (coefficient = 0.74), low baseline overactive bladder symptoms score (coefficient = -0.12) and the presence of OAB-wet (coefficient = 0.79) were independent factors associated with therapeutic efficacy (i.e., GRA score). VE (odds ratio = 0.062) was the only predictor for a large PVR at 3 months. The optimum cutoff value of VE was <87% with the area under the ROC curve being 0.64 (sensitivity = 63.8%, specificity = 57.1%). CONCLUSIONS: The therapeutic effects of Botox can persist till 6 months after treatment. Female gender, low overactive bladder symptoms score and OAB-wet are associated better therapeutic efficacy, and low baseline VE is associated with large PVR. These findings can serve as an initial guide or assist in consultation regarding the treatment of OAB patients with Botox injection. TRIAL REGISTRATION: ClinicalTrials.gov NCT01657409. PMID- 26824902 TI - A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease. AB - BACKGROUND: Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings. METHODS: Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista(r)) and liquid based cervical cytology (LBC ThinPrep(r)). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration. RESULTS: A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6 73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions. CONCLUSIONS: These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy. TRIAL REGISTRATION: ISRCTN Registry 48776874. PMID- 26824903 TI - Intrahepatic Tissue Implantation Represents a Favorable Approach for Establishing Orthotopic Transplantation Hepatocellular Carcinoma Mouse Models. AB - Mouse models are commonly used for studying hepatocellular carcinoma (HCC) biology and exploring new therapeutic interventions. Currently three main modalities of HCC mouse models have been extensively employed in pre-clinical studies including chemically induced, transgenic and transplantation models. Among them, transplantation models are preferred for evaluating in vivo drug efficacy in pre-clinical settings given the short latency, uniformity in size and close resemblance to tumors in patients. However methods used for establishing orthotopic HCC transplantation mouse models are diverse and fragmentized without a comprehensive comparison. Here, we systemically evaluate four different approaches commonly used to establish HCC mice in preclinical studies, including intravenous, intrasplenic, intrahepatic inoculation of tumor cells and intrahepatic tissue implantation. Four parameters--the latency period, take rates, pathological features and metastatic rates--were evaluated side-by-side. 100% take rates were achieved in liver with intrahepatic, intrasplenic inoculation of tumor cells and intrahepatic tissue implantation. In contrast, no tumor in liver was observed with intravenous injection of tumor cells. Intrahepatic tissue implantation resulted in the shortest latency with 0.5 cm (longitudinal diameter) tumors found in liver two weeks after implantation, compared to 0.1cm for intrahepatic inoculation of tumor cells. Approximately 0.1cm tumors were only visible at 4 weeks after intrasplenic inoculation. Uniform, focal and solitary tumors were formed with intrahepatic tissue implantation whereas multinodular, dispersed and non-uniform tumors produced with intrahepatic and intrasplenic inoculation of tumor cells. Notably, metastasis became visible in liver, peritoneum and mesenterium at 3 weeks post-implantation, and lung metastasis was visible after 7 weeks. T cell infiltration was evident in tumors, resembling the situation in HCC patients. Our study demonstrated that orthotopic HCC mouse models established via intrahepatic tissue implantation authentically reflect clinical manifestations in HCC patients pathologically and immunologically, suggesting intrahepatic tissue implantation is a preferable approach for establishing orthotopic HCC mouse models. PMID- 26824905 TI - The Use of Intravenous Acetaminophen for Acute Pain in the Emergency Department. AB - OBJECTIVES: Acetaminophen (APAP) is a mainstay for pain management worldwide. The intravenous (IV) formulation has been widely used in Europe for more than 20 years in adults and children. In the United States, IV APAP obtained full approval from the Food and Drug Administration in 2010. There is emerging literature to suggest the use of IV APAP for pain reduction in the emergency department (ED). This evidence-based review examines the evidence pertaining to the use of IV APAP for acute pain control in the ED. METHODS: The MEDLINE and EMBASE databases were searched. Randomized controlled trials (RCTs) that described or evaluated the use of IV APAP for acute pain in the ED were included. Duplicate articles, unpublished reports, abstracts, review articles, and non English literature were excluded. The primary outcome of interest in this review was the difference in pain score between IV APAP and active comparator or placebo from baseline to a cutoff time specified in the original trials. Secondary outcome measures were the incidence of adverse events and reduction in the amount of adjuvant analgesics consumed by patients who received IV APAP. Methodologic quality of the trials was assessed using the Grading of Recommendations Assessment, Development, and Evaluation criteria. RESULTS: Fourteen RCTs with various methodologic flaws, which enrolled a total of 1,472 patients, met the inclusion criteria. The level of evidence for the individual trials ranged from very low to moderate. In three of the 14 trials, a significant reduction in pain scores was observed in patients who received IV APAP. The first trial found a significant reduction in mean pain scores when IV APAP was compared to IV morphine at 30 minutes after drug administration (4.7 +/- 2.3 vs. 2.9 +/- 2.2). In the second trial, patients who received IV APAP reported of lower pain scores (31.7 +/- 18 mm, 95% confidence interval [CI] = 8.2 to 25.2 mm) compared to those who received IV morphine (48.3 +/- 14.1 mm, 95% CI = 8.2 to 25.2 mm), 15 minutes after drug administration. A third trial found a significant reduction (p = 0.005) in the mean pain scores when IV APAP was compared to intramuscular piroxicam at 90 minutes after drug administration. In the remaining eight trials, pain scores were not statistically different when IV APAP was compared to other pain medications. The incidence of side effects associated with IV APAP was very low. CONCLUSIONS: Fourteen RCTs with various methodologic flaws provided limited evidence to support the use of IV APAP as the primary analgesic for acute pain control in patients who present to the ED. PMID- 26824904 TI - AMP-Activated Protein Kinase Regulates Oxidative Metabolism in Caenorhabditis elegans through the NHR-49 and MDT-15 Transcriptional Regulators. AB - Cellular energy regulation relies on complex signaling pathways that respond to fuel availability and metabolic demands. Dysregulation of these networks is implicated in the development of human metabolic diseases such as obesity and metabolic syndrome. In Caenorhabditis elegans the AMP-activated protein kinase, AAK, has been associated with longevity and stress resistance; nevertheless its precise role in energy metabolism remains elusive. In the present study, we find an evolutionary conserved role of AAK in oxidative metabolism. Similar to mammals, AAK is activated by AICAR and metformin and leads to increased glycolytic and oxidative metabolic fluxes evidenced by an increase in lactate levels and mitochondrial oxygen consumption and a decrease in total fatty acids and lipid storage, whereas augmented glucose availability has the opposite effects. We found that these changes were largely dependent on the catalytic subunit AAK-2, since the aak-2 null strain lost the observed metabolic actions. Further results demonstrate that the effects due to AAK activation are associated to SBP-1 and NHR-49 transcriptional factors and MDT-15 transcriptional co activator, suggesting a regulatory pathway that controls oxidative metabolism. Our findings establish C. elegans as a tractable model system to dissect the relationship between distinct molecules that play a critical role in the regulation of energy metabolism in human metabolic diseases. PMID- 26824907 TI - Correction: Correction: Socio-Economic Differentials in Impoverishment Effects of Out-of-Pocket Health Expenditure in China and India: Evidence from WHO SAGE. PMID- 26824906 TI - No Evidence of a Common DNA Variant Profile Specific to World Class Endurance Athletes. AB - There are strong genetic components to cardiorespiratory fitness and its response to exercise training. It would be useful to understand the differences in the genomic profile of highly trained endurance athletes of world class caliber and sedentary controls. An international consortium (GAMES) was established in order to compare elite endurance athletes and ethnicity-matched controls in a case control study design. Genome-wide association studies were undertaken on two cohorts of elite endurance athletes and controls (GENATHLETE and Japanese endurance runners), from which a panel of 45 promising markers was identified. These markers were tested for replication in seven additional cohorts of endurance athletes and controls: from Australia, Ethiopia, Japan, Kenya, Poland, Russia and Spain. The study is based on a total of 1520 endurance athletes (835 who took part in endurance events in World Championships and/or Olympic Games) and 2760 controls. We hypothesized that world-class athletes are likely to be characterized by an even higher concentration of endurance performance alleles and we performed separate analyses on this subsample. The meta-analysis of all available studies revealed one statistically significant marker (rs558129 at GALNTL6 locus, p = 0.0002), even after correcting for multiple testing. As shown by the low heterogeneity index (I2 = 0), all eight cohorts showed the same direction of association with rs558129, even though p-values varied across the individual studies. In summary, this study did not identify a panel of genomic variants common to these elite endurance athlete groups. Since GAMES was underpowered to identify alleles with small effect sizes, some of the suggestive leads identified should be explored in expanded comparisons of world-class endurance athletes and sedentary controls and in tightly controlled exercise training studies. Such studies have the potential to illuminate the biology not only of world class endurance performance but also of compromised cardiac functions and cardiometabolic diseases. PMID- 26824910 TI - Validation of the Martin Method for Estimating Low-Density Lipoprotein Cholesterol Levels in Korean Adults: Findings from the Korea National Health and Nutrition Examination Survey, 2009-2011. AB - Despite the importance of accurate assessment for low-density lipoprotein cholesterol (LDL-C), the Friedewald formula has primarily been used as a cost effective method to estimate LDL-C when triglycerides are less than 400 mg/dL. In a recent study, an alternative to the formula was proposed to improve estimation of LDL-C. We evaluated the performance of the novel method versus the Friedewald formula using a sample of 5,642 Korean adults with LDL-C measured by an enzymatic homogeneous assay (LDL-CD). Friedewald LDL-C (LDL-CF) was estimated using a fixed factor of 5 for the ratio of triglycerides to very-low-density lipoprotein cholesterol (TG:VLDL-C ratio). However, the novel LDL-C (LDL-CN) estimates were calculated using the N-strata-specific median TG:VLDL-C ratios, LDL-C5 and LDL C25 from respective ratios derived from our data set, and LDL-C180 from the 180 cell table reported by the original study. Compared with LDL-CF, each LDL-CN estimate exhibited a significantly higher overall concordance in the NCEP-ATP III guideline classification with LDL-CD (p< 0.001 for each comparison). Overall concordance was 78.2% for LDL-CF, 81.6% for LDL-C5, 82.3% for LDL-C25, and 82.0% for LDL-C180. Compared to LDL-C5, LDL-C25 significantly but slightly improved overall concordance (p = 0.008). LDL-C25 and LDL-C180 provided almost the same overall concordance; however, LDL-C180 achieved superior improvement in classifying LDL-C < 70 mg/dL compared to the other estimates. In subjects with triglycerides of 200 to 399 mg/dL, each LDL-CN estimate showed a significantly higher concordance than that of LDL-CF (p< 0.001 for each comparison). The novel method offers a significant improvement in LDL-C estimation when compared with the Friedewald formula. However, it requires further modification and validation considering the racial differences as well as the specific character of the applied measuring method. PMID- 26824911 TI - Outcome predictors of treatment effectiveness for fungal malignant external otitis: a systematic review. AB - The aim of this review is to summarise literature data on clinical aspects and traditional management of fungal malignant external otitis (FMEO), and to identify potential predictive factors of positive treatment outcome. Articles were initially selected based on their titles or abstracts. Full articles were then retrieved and further scrutinised according to predetermined criteria. Reference lists of selected articles were searched for any missed publications. The selected articles were methodologically evaluated. Of an initial 143 references, 14 were selected that focalised on the management of FMEO. The majority of studies demonstrated a correlation between treatment effectiveness, assessed as symptom resolution, and clinical and management variables: abstention from surgical debridement, absence of facial palsy, Aspergillus spp. as causative pathogen and absence of imaging findings at diagnosis and follow-up. The effectiveness of FMEO treatment depends on the assessment of cranial nerve state, the causative pathogen and imaging findings. Above all, absence of facial nerve palsy, Aspergillus spp. and absence of radiological signs at diagnosis and during follow-up correlate with symptom resolution. The fact that conservative treatment may be associated with a better outcome than surgical debridement could purely reflect that patients with more aggressive and advanced illness required debridement, whereas milder disease was treated conservatively. Thus, caution should be advised in the interpretation of data due to the need for further trials on the topic. PMID- 26824912 TI - Differential diagnosis of parotid gland tumours: which magnetic resonance findings should be taken in account? AB - Our aim was to define typical magnetic resonance (MRI) findings in malignant and benign parotid tumours. This study is based on retrospective evaluation of pre surgical MRI of 94 patients with parotid gland tumours. Histology results were available for all tumours. There were 69 cases of benign (73%) and 25 cases of malignant (27%) tumours, including 44 pleomorphic adenomas, 18 Warthin's tumours, 7 various benign tumours, 6 squamous cell carcinomas, 3 carcinoma ex pleomorphic adenomas, 2 mucoepidermoid carcinomas, 1 adenoid cystic carcinoma and 13 various malignant tumours. The following MRI parameters were evaluated: shape, site, size, margins, signal intensity (SI) on T1w and T2w images, contrast enhancement, signal of cystic content, presence or absence of a capsule, perineural spread, extraglandular growth pattern and cervical adenopathy. Statistical analysis was performed to identify the MRI findings most suggestive of malignancy, and to define the most typical MRI pattern of the most common histologies. Ill-defined margins (p < 0.001), adenopathies (p < 0.001) and infiltrative grown pattern (p < 0.001) were significantly predictive of malignancy. Typical findings of pleomorphic adenoma included hyperintensity on T2w images (p = 0.02), strong contrast enhancement (p < 0.001) and lobulated shape (p = 0.04). Typical findings of Warthin's tumour included hyperintense components on T1w images (p < 0.001), location in the parotid inferior process (p < 0.001) and mild or incomplete contrast enhancement (p = 0.01). SI on T1w and T2w images and contrast enhancement enables differential diagnosis between pleomorphic adenoma and Warthin's tumour. PMID- 26824913 TI - Macrophageal infiltration and microvessel density in laryngeal carcinoma: study of 52 cases. AB - Angiogenesis is one of the six originally constituted hallmarks of cancer that has been extensively studied in the last two decades. The aim of our study is to assess the microvessel and macrophageal density in laryngeal carcinoma and its clinicopathological correlations. We immunohistochemically assessed microvessel density (CD34) and macrophage count (CD68) using microarray techniques and then looked for clinicopathological correlations. The mean micro-vessel density in the study group was 14.27 +/- 12.92 vessels in a *200 field with a mean macrophageal infiltration density of 5.19 +/- 4.32. Median microvessel density was significantly higher in patients with metastasis than in patients without metastasis. Additionally, linear regression established that macrophageal infiltration density could predict microvessel density in laryngeal carcinoma. We found no association between either factor and recurrence rate or other clinical characteristics. Our study adds additional data to a problem that has been widely studied during the last two decades, even if controversies in this area still remain. PMID- 26824914 TI - Learning curve in diagnostic and interventional sialendoscopy for obstructive salivary diseases. AB - Sialendoscopy is a new diagnostic and surgical tool for management of salivary gland diseases that offers the opportunity to treat selected pathologies less invasively and with better results compared to previous techniques. As with any new technique, an adequate training programme involving a gradual learning curve is mandatory to quickly obtain results similar to those reported in the literature. This includes an appropriate diagnostic programme, correct patient selection and knowledge of possible pitfalls. In this retrospective study, the outcomes of the first 141 procedures (74 on the parotid gland and 67 on the submandibular gland) performed with this technique in our Department from 2009 to 2013 were compared with those reported in the literature. Patients were divided into three groups: Group A (the first 49 procedures performed), Group B (the next 50 procedures), and Group C (the last 42 procedures). There were no statistically significant differences relative to mean procedure times, recurrence of symptomatology after treatment, need for further treatments and rates of minor complications between groups. No major complications were seen. The increase in experience resulted in an increased number of interventional sialendoscopies performed under local anaesthesia instead of general anaesthesia (51% vs 18% vs 14%). In only three of 130 glands treated (2.3%) was gland resection required. We also evaluated which technique had been used for stone removal and rate of failure, which was similar in all groups (13.6% vs 15% vs 15%). Our results do not substantially differ from those reported in the literature. Initial difficulties in catheterising the papilla could be overcome with practise on fresh human specimens or fresh pig heads. Lack of precision regarding diagnostic imaging techniques was remedied by improving the competence of the surgeon in performing pre- and postoperative ultrasound. The creation of specialised centres capable of treating up to 1 to 2 million people would be desirable in order to better stratify pathologies, validate the investment in equipment and gain the necessary experience in the various surgical techniques. PMID- 26824915 TI - Which cephalometric analysis for maxillo-mandibular surgery in patients with obstructive sleep apnoea syndrome? AB - Maxillo-mandibular advancement MMA is considered an efficacious treatment for patients affected by severe obstructive sleep apnoea syndrome (OSAS). Even though OSAS improvement is the main goal of MMA, excessive maxillo-mandibular protrusion should be avoided to guarantee pleasant postoperative facial aesthetics. In order to attain such a result, the amount of MMA should be planned preoperatively by both aesthetic and cephalometric analyses. Steiner and Delaire cephalometric analyses are commonly used in the preoperative planning of orthognatic surgery for dentofacial deformities, however controversies still exist about the basis and postoperative aesthetic results of such cephalometric analyses in OSAS patients candidate for MMA. Forty-eight patients affected by severe OSAS were submitted to MMA. Pre- and post-operative Steiner and Delaire cephalometric tracings were assessed in each subject. For Steiner analysis, the variation in the SNA and SNB angles was measured, while for Delaire tracings the variation in the C3/FM-CPA and C3/FM-Me angles was assessed. Mean MMA was 6.9 + 3.8 mm for the maxilla and 13.6 + 5 mm for the mandible. After surgery, an improvement of the apnoea-hypopnoea index was recorded (40.47 + 7.64 preoperative vs. 12.56 + 5.78 postoperative). In all patients, both cephalometric analyses showed presurgical bimaxillary retrusion. After surgery, the mean value of Steiner's SNA angle increased from 78.18 degrees to 85.58 degrees (p < 0.001), while mean Delaire's C3/FM-CPA angle increased from 81.19 degrees to 89.71 degrees (p < 0.001). The mean value of Steiner's SNB angle increased from 74.33 degrees to 80.73 degrees (p < 0.001), while Delaire's C3/FM-Me angle increased from 80.10 degrees to 87.29 degrees (p < 0.001). Postoperatively, both the maxilla and mandible were in a more protrusive position (p < 0.001) according to Steiner analysis compared with Delaire tracing. Basing MMA on Delaire cephalometric analysis leads to an increased advancement of the maxillo-mandibular complex than Steiner tracing. The consequences of this aspect on facial aesthetics should be considered during surgical planning and preoperative informed consent in OSAS patients candidate for MMA. PMID- 26824916 TI - Cartilage ossiculoplasty in cholesteatoma surgery: hearing results and prognostic factors. AB - Cartilage tympanoplasty is an established procedure for tympanic membrane and attic reconstruction. Cartilage has been used as an ossiculoplasty material for many years. The aim of this study was to evaluate hearing results of costal cartilage prostheses in ossicular chain reconstruction procedures in subjects operated on for middle ear cholesteatoma and to determine the presence of prognostic factors. Candidates for this study were patients affected by middle ear cholesteatoma whose ossicular chain was reconstructed with a chondroprosthesis. 67 cases of ossiculoplasty with total (TORP) or partial (PORP) chondroprosthesis were performed between January 2011 and December 2013. Follow up examination included micro-otoscopy and pure tone audiometry. The guidelines of the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology Head and Neck Surgery were followed and pure-tone average (PTA) was calculated as the mean of 0.5, 1, 2 and 4 kHz thresholds. Statistical analysis was performed with ANOVA tests and regression models. Average air-bone gap (ABG) significantly improved from 39.2 dB HL (SD 9.1 dB HL) to 25.4 dB HL (SD 11 dB HL) (p < 0.001). Linear regression analysis showed that the only prognostic factor was the type of operation (p = 0.02). In fact, patients submitted to ICWT presented better post-operative ABG compared to CWDT. None of the other variables influenced the results. The present study proposes costal cartilage as material of choice when autologous ossicles are not available. The maintenance of the posterior canal wall was the only prognostic factor identified. PMID- 26824917 TI - Binaural squelch and head shadow effects in children with unilateral cochlear implants and contralateral hearing aids. AB - The aim of this study was to investigate the amount of binaural squelch effect (BSE) and head shadow effect (HSE) in children who use unilateral cochlear implants (CI) and contralateral hearing aids (HA). The study group consisted of 19 CI recipient children who consistently wore a contralateral HA. Speech sounds were used to evaluate speech perception performance in noise. Testing was performed in three listening conditions: (1) bimodal listening with noise source on HA side; (2) CI only with noise source contralaterally (HA off); (3) CI only with noise source on the CI side. Statistical analysis revealed a significant difference between the three listening conditions and post hoc tests indicated significant differences for all pairwise comparisons (p < 0.001). The average BSE and HSE were 11.8% and 17.1% respectively. The majority of bimodal CI users showed BSE and HSE with significant speech perception improvement in the presence of noise. PMID- 26824918 TI - 3D computed tomographic evaluation of the upper airway space of patients undergoing mandibular distraction osteogenesis for micrognathia. AB - Mandibular distraction osteogenesis (MDO) is currently an accepted method of treatment for patients requiring reconstruction of hypoplastic mandibles. To date one of the unsolved problems is how to assess the quantitative increase of mandible length needed to achieve a significant change in the volume of the posterior airway space (PAS) in children with mandibular micrognathia following distraction osteogenesis. The purpose of this study is to present quantitative volumetric evaluation of PAS in young patients having distraction osteogenesis for micrognathia using 3D-CT data sets and compare it with pre-operative situation. In this observational retrospective study, we report our experience in five consecutive patients who underwent MDO in an attempt to relieve severe upper airway obstruction. Each patient was evaluated before treatment (T0) and at the end of distraction procedure (T1) with computer tomography (CT) in axial, coronal, and sagittal planes and three-dimensional CT of the facial bones and upper airway. Using parameters to extract only data within anatomic constraints, a digital set of the edited upper airway volume was obtained. The volume determination was used for volumetric qualification of upper airway. The computed tomographic digital data were used to evaluate the upper airway volumes both pre distraction and post-distraction. The mean length of distraction was 23 mm. Quantitative assessment of upper airway volume before and after distraction demonstrated increased volumes ranging from 84% to 3,087% with a mean of 536%. In conclusion, our study seems to show that DO can significantly increase the volume of the PAS in patients with upper airway obstruction following micrognathia, by an average of 5 times. Furthermore, the worse is the starting volume, the greater the increase in PAS to equal distraction. PMID- 26824921 TI - Bleomycin sclerotherapy for lymphatic malformation after unsuccessful surgical excision: case report. AB - Lymphatic malformations (LMs) are benign cystic masses resulting from the abnormal development of lymphatic channels. Lymphatic malformations occur primarily in the head and neck region. Surgical excision of lymphatic malformation is followed by high rate of recurrence and a high risk of complications. Bleomycin is an established antineoplastic drug. It can be used as a sclerosing agent in vascular anomalies. We present a child who was unsuccessfully treated with four surgical resections, with peripheral palsy of facial nerve as complication. The lymphatic malformation was successfully treated in our institution with intralesional administration of bleomycin. PMID- 26824920 TI - Surgical approach to isolated bilateral orbital floor fractures. AB - Isolated bilateral orbital floor fractures are uncommon and are rarely described in the scientific literature. They are usually seen in association with naso ethmoidal fractures, zygomatic fractures, or fractures of the middle third. We report our experience in the management of a patient presenting bilateral isolated orbital floor fracture. The difficulties in management of these fractures are due to the lack of an uninjured contralateral side for intraoperative comparison. PMID- 26824919 TI - Ossifying fibromas of the paranasal sinuses: diagnosis and management. AB - Fibro-osseous benign lesions rarely affect the sinonasal tract and are divided into 3 different entities, namely osteoma, fibrous dysplasia and ossifying fibroma. They share several clinical, radiological and histological similarities, but have different behaviours. Ossifying fibroma, and in particular the "juvenile" histological subtype, may have a locally aggressive evolution and a high risk for recurrence if removal is incomplete. The purpose of the present study is to compare the clinical behaviour of ossifying fibroma with the other benign fibro-osseous lesions; highlight different behaviour between the histological subtypes; compare the advantages, limitations and outcomes of an endoscopic endonasal approach with reports in the literature. We retrospectively reviewed 11 patients treated for sinonasal ossifying fibroma at a tertiary care centre. All patients underwent CT scan, and MRI was performed in cases of cranial base involvement or recurrence. Pre-operative biopsy was performed in cases where it was possible to use an endoscopic approach. One patient underwent pre operative embolisation with ipsilateral visual loss after the procedure. Depending on its location, removal of the tumour was performed using an endoscopic (n = 7), or an external (n = 3) or combined (n = 1) approach. Histopathologically, 5 patients presented the conventional type, 5 the juvenile psammomatoid variant, which was associated in 1 case with an aneurismal bone cyst, and 1 case presented the trabecular juvenile variant. Three patients affected by the juvenile psammomatoid histological variant presented invasion of the skull base and underwent a subtotal removal that subsequently required, due to the regrowth of the remnant, a transbasal approach. Clinical, radiological and histological findings should all be considered to establish differential diagnosis among fibrous osseous lesions. More studies are necessary to conclude if the localisation and extension of the disease at the time of diagnosis is more important than the histological variant. An endoscopic approach is the first choice in most of cases even if an external open approach may be necessary in selected patients. PMID- 26824922 TI - Locally adaptive 2D-3D registration using vascular structure model for liver catheterization. AB - Two-dimensional-three-dimensional (2D-3D) registration between intra-operative 2D digital subtraction angiography (DSA) and pre-operative 3D computed tomography angiography (CTA) can be used for roadmapping purposes. However, through the projection of 3D vessels, incorrect intersections and overlaps between vessels are produced because of the complex vascular structure, which makes it difficult to obtain the correct solution of 2D-3D registration. To overcome these problems, we propose a registration method that selects a suitable part of a 3D vascular structure for a given DSA image and finds the optimized solution to the partial 3D structure. The proposed algorithm can reduce the registration errors because it restricts the range of the 3D vascular structure for the registration by using only the relevant 3D vessels with the given DSA. To search for the appropriate 3D partial structure, we first construct a tree model of the 3D vascular structure and divide it into several subtrees in accordance with the connectivity. Then, the best matched subtree with the given DSA image is selected using the results from the coarse registration between each subtree and the vessels in the DSA image. Finally, a fine registration is conducted to minimize the difference between the selected subtree and the vessels of the DSA image. In experimental results obtained using 10 clinical datasets, the average distance errors in the case of the proposed method were 2.34+/-1.94mm. The proposed algorithm converges faster and produces more correct results than the conventional method in evaluations on patient datasets. PMID- 26824923 TI - Analysis of the Transcriptome of the Infective Stage of the Beet Cyst Nematode, H. schachtii. AB - The beet cyst nematode, Heterodera schachtii, is a major root pest that significantly impacts the yield of sugar beet, brassicas and related species. There has been limited molecular characterisation of this important plant pathogen: to identify target genes for its control the transcriptome of the pre parasitic J2 stage of H. schachtii was sequenced using Roche GS FLX. Ninety seven percent of reads (i.e., 387,668) with an average PHRED score > 22 were assembled with CAP3 and CLC Genomics Workbench into 37,345 and 47,263 contigs, respectively. The transcripts were annotated by comparing with gene and genomic sequences of other nematodes and annotated proteins on public databases. The annotated transcripts were much more similar to sequences of Heterodera glycines than to those of Globodera pallida and root knot nematodes (Meloidogyne spp.). Analysis of these transcripts showed that a subset of 2,918 transcripts was common to free-living and plant parasitic nematodes suggesting that this subset is involved in general nematode metabolism and development. A set of 148 contigs and 183 singletons encoding putative homologues of effectors previously characterised for plant parasitic nematodes were also identified: these are known to be important for parasitism of host plants during migration through tissues or feeding from cells or are thought to be involved in evasion or modulation of host defences. In addition, the presence of sequences from a nematode virus is suggested. The sequencing and annotation of this transcriptome significantly adds to the genetic data available for H. schachtii, and identifies genes primed to undertake required roles in the critical pre-parasitic and early post-parasitic J2 stages. These data provide new information for identifying potential gene targets for future protection of susceptible crops against H. schachtii. PMID- 26824924 TI - Genomic Prediction of Testcross Performance in Canola (Brassica napus). AB - Genomic selection (GS) is a modern breeding approach where genome-wide single nucleotide polymorphism (SNP) marker profiles are simultaneously used to estimate performance of untested genotypes. In this study, the potential of genomic selection methods to predict testcross performance for hybrid canola breeding was applied for various agronomic traits based on genome-wide marker profiles. A total of 475 genetically diverse spring-type canola pollinator lines were genotyped at 24,403 single-copy, genome-wide SNP loci. In parallel, the 950 F1 testcross combinations between the pollinators and two representative testers were evaluated for a number of important agronomic traits including seedling emergence, days to flowering, lodging, oil yield and seed yield along with essential seed quality characters including seed oil content and seed glucosinolate content. A ridge-regression best linear unbiased prediction (RR BLUP) model was applied in combination with 500 cross-validations for each trait to predict testcross performance, both across the whole population as well as within individual subpopulations or clusters, based solely on SNP profiles. Subpopulations were determined using multidimensional scaling and K-means clustering. Genomic prediction accuracy across the whole population was highest for seed oil content (0.81) followed by oil yield (0.75) and lowest for seedling emergence (0.29). For seed yieId, seed glucosinolate, lodging resistance and days to onset of flowering (DTF), prediction accuracies were 0.45, 0.61, 0.39 and 0.56, respectively. Prediction accuracies could be increased for some traits by treating subpopulations separately; a strategy which only led to moderate improvements for some traits with low heritability, like seedling emergence. No useful or consistent increase in accuracy was obtained by inclusion of a population substructure covariate in the model. Testcross performance prediction using genome-wide SNP markers shows considerable potential for pre-selection of promising hybrid combinations prior to resource-intensive field testing over multiple locations and years. PMID- 26824925 TI - Current Staging Procedures in Urinary Bladder Cancer. AB - Currently computed tomography (CT) represents the most widely used standard imaging modality in muscle-invasive urinary bladder cancer. Visualization of local tumor or depth of invasion as well as lymph node staging, however, is often impaired. Magnetic resonance imaging (MRI) with diffusion-weighted sequences, determination of apparent diffusion coefficient (ADC) values or utilization of superparamagnetic iron nanoparticles potentially exhibits advantages in the assessment of local tumor or lymph node involvement and therefore might play a role in routine staging of urinary bladder cancer in the future. Likewise, positron emission tomography (PET) with the currently utilized tracers (18)F-FDG, (11)C-choline and (11)C-acetate is investigated in bladder cancer patients-mostly in combination with diagnostic CT. Although promising results could be obtained for these PET/CT examinations in smaller series, their true value cannot be determined at present. PMID- 26824926 TI - A Multi-Camera System for Bioluminescence Tomography in Preclinical Oncology Research. AB - Bioluminescent imaging (BLI) of cells expressing luciferase is a valuable noninvasive technique for investigating molecular events and tumor dynamics in the living animal. Current usage is often limited to planar imaging, but tomographic imaging can enhance the usefulness of this technique in quantitative biomedical studies by allowing accurate determination of tumor size and attribution of the emitted light to a specific organ or tissue. Bioluminescence tomography based on a single camera with source rotation or mirrors to provide additional views has previously been reported. We report here in vivo studies using a novel approach with multiple rotating cameras that, when combined with image reconstruction software, provides the desired representation of point source metastases and other small lesions. Comparison with MRI validated the ability to detect lung tumor colonization in mouse lung. PMID- 26824927 TI - Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with (177)Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor. AB - Peptide receptor radionuclide therapy (PRRT) is a relatively new mode of internally targeted radiotherapy currently in clinical trials. In PRRT, ionizing radioisotopes conjugated to somatostatin analogues are targeted to neuroendocrine tumors (NETs) via somatostatin receptors. Despite promising clinical results, very little is known about the mechanism of tumor control. By using NCI-H727 cells in an in vivo murine xenograft model of human NETs, we showed that (177)Lu DOTATATE PRRT led to increased infiltration of CD86+ antigen presenting cells into tumor tissue. We also found that following treatment with PRRT, there was significantly increased tumor infiltration by CD49b+/FasL+ NK cells potentially capable of tumor killing. Further investigation into the immunomodulatory effects of PRRT will be essential in improving treatment efficacy. PMID- 26824928 TI - Functional Imaging in Diagnostic of Orthopedic Implant-Associated Infections. AB - Surgeries' sterile conditions and perioperative antibiotic therapies decrease implant associated infections rates significantly. However, up to 10% of orthopedic devices still fail due to infections. An implant infection generates a high socio-economic burden. An early diagnosis of an infection would significantly improve patients' outcomes. There are numerous clinical tests to diagnose infections. The "Gold Standard" is a microbiological culture, which requires an invasive sampling and lasts up to several weeks. None of the existing tests in clinics alone is sufficient for a conclusive diagnosis of an infection. Meanwhile, there are functional imaging modalities, which hold the promise of a non-invasive, quick, and specific infection diagnostic. This review focuses on orthopedic implant-associated infections, their pathogenicity, diagnosis and functional imaging. PMID- 26824929 TI - Gene Expression of Glucose Transporter 1 (GLUT1), Hexokinase 1 and Hexokinase 2 in Gastroenteropancreatic Neuroendocrine Tumors: Correlation with F-18 fluorodeoxyglucose Positron Emission Tomography and Cellular Proliferation. AB - Neoplastic tissue exhibits high glucose utilization and over-expression of glucose transporters (GLUTs) and hexokinases (HKs), which can be imaged by (18)F Fluorodeoxyglucose-positron emission tomography (FDG-PET). The aim of the present study was to investigate the expression of glycolysis-associated genes and to compare this with FDG-PET imaging as well as with the cellular proliferation index in two cancer entities with different malignant potential. Using real-time PCR, gene expression of GLUT1, HK1 and HK2 were studied in 34 neuroendocrine tumors (NETs) in comparison with 14 colorectal adenocarcinomas (CRAs). The Ki67 proliferation index and, when available, FDG-PET imaging was compared with gene expression. Overexpression of GLUT1 gene expression was less frequent in NETs (38%) compared to CRAs (86%), P = 0.004. HK1 was overexpressed in 41% and 71% of NETs and CRAs, respectively (P = 0.111) and HK2 was overexpressed in 50% and 64% of NETs and CRAs, respectively (P = 0.53). There was a significant correlation between the Ki67 proliferation index and GLUT1 gene expression for the NETs (R = 0.34, P = 0.047), but no correlation with the hexokinases. FDG-PET identified foci in significantly fewer NETs (36%) than CRAs (86%), (P = 0.04). The gene expression results, with less frequent GLUT1 and HK1 upregulation in NETs, confirmed the lower metabolic activity of NETs compared to the more aggressive CRAs. In accordance with this, fewer NETs were FDG-PET positive compared to CRA tumors and FDG uptake correlated with GLUT1 gene expression. PMID- 26824931 TI - Leg Regrowth in Blaberus discoidalis (Discoid Cockroach) following Limb Autotomy versus Limb Severance and Relevance to Neurophysiology Experiments. AB - BACKGROUND: Many insects can regenerate limbs, but less is known about the regrowth process with regard to limb injury type. As part of our neurophysiology education experiments involving the removal of a cockroach leg, 1) the ability of Blaberus discoidalis cockroaches to regenerate a metathoracic leg was examined following autotomy at the femur/trochanter joint versus severance via a transverse coxa-cut, and 2) the neurophysiology of the detached legs with regard to leg removal type was studied by measuring spike firing rate and microstimulation movement thresholds. LEG REGROWTH RESULTS: First appearance of leg regrowth was after 5 weeks in the autotomy group and 12 weeks in the coxa-cut group. Moreover, regenerated legs in the autotomy group were 72% of full size on first appearance, significantly larger (p<0.05) than coxa-cut legs (29% of full size at first appearance). Regenerated legs in both groups grew in size with each subsequent molt; the autotomy-removed legs grew to full size within 18 weeks, whereas coxa-cut legs took longer than 28 weeks to regrow. Removal of the metathoracic leg in both conditions did not have an effect on mortality compared to matched controls with unmolested legs. NEUROPHYSIOLOGY RESULTS: Autotomy removed legs had lower spontaneous firing rates, similar marked increased firing rates upon tactile manipulation of tibial barbs, and a 10% higher electrical microstimulation threshold for movement. SUMMARY: It is recommended that neurophysiology experiments on cockroach legs remove the limb at autotomy joints instead of coxa cuts, as the leg regenerates significantly faster when autotomized and does not detract from the neurophysiology educational content. PMID- 26824930 TI - Continuous Glucose Monitoring Systems: A Review. AB - There have been continuous advances in the field of glucose monitoring during the last four decades, which have led to the development of highly evolved blood glucose meters, non-invasive glucose monitoring (NGM) devices and continuous glucose monitoring systems (CGMS). Glucose monitoring is an integral part of diabetes management, and the maintenance of physiological blood glucose concentration is the only way for a diabetic to avoid life-threatening diabetic complications. CGMS have led to tremendous improvements in diabetic management, as shown by the significant lowering of glycated hemoglobin (HbA1c) in adults with type I diabetes. Most of the CGMS have been minimally-invasive, although the more recent ones are based on NGM techniques. This manuscript reviews the advances in CGMS for diabetes management along with the future prospects and the challenges involved. PMID- 26824933 TI - Systemic Exposures of Fluticasone Propionate and Salmeterol Following Inhalation via Metered Dose Inhaler with the Mini Spacer Compared with the Aerochamber Plus Spacer. AB - BACKGROUND: The Mini Spacer has been developed for use with Ventolin((r)) metered dose inhalers (MDIs) to improve accessibility to affordable spacers in developing countries. To ensure patient safety is not compromised if the Mini Spacer is used off-label with fluticasone propionate (FP) or salmeterol/FP combination (SFC) MDIs (currently not recommended), this study compared the systemic exposure of FP and salmeterol following delivery of FP and SFC MDIs with the Mini Spacer and the Aerochamber Plus((r)) spacer (Aerochamber). METHODS: This was an open-label, randomized, single dose, crossover study in healthy subjects that evaluated four treatments: i) FP 250 MUg MDI with Mini Spacer; ii) FP 250 MUg MDI with Aerochamber; iii) SFC 25/250 MUg with Mini Spacer; iv) SFC 25/250 MUg with Aerochamber. There was a minimum 7 day washout between treatments. Pharmacokinetic samples were collected over 24 hours post-dose. The co-primary endpoints were FP area under the concentration-time curve from time zero to 24 h [FP AUC(0-24)] and salmeterol maximum plasma concentration [Cmax]. RESULTS: FP systemic exposure in terms of AUC(0-24) was lower following inhalation with the Mini Spacer compared with the Aerochamber for both FP 250 MUg (Mini Spacer/Aerochamber Ratio 0.76 [90% CI: 0.57-1.01]) and SFC 25/250 MUg (Ratio 0.74 [90% CI: 0.56-0.99]). Salmeterol systemic exposure was also lower following SFC 25/250 MUg with Mini Spacer compared with Aerochamber (Cmax Ratio 0.90 [90% CI 0.48-1.66]). The incidence of adverse events was low and similar with each treatment. CONCLUSIONS: In the event of use of the Mini Spacer with FP and SFC MDIs, which is not recommended, FP and salmeterol systemic exposure is unlikely to be higher than if MDIs were to be used with the Aerochamber. However, these data do not indicate that the Mini Spacer and Aerochamber are interchangeable. PMID- 26824934 TI - Mechanisms of in vivo muscle fatigue in humans: investigating age-related fatigue resistance with a computational model. AB - KEY POINTS: Muscle fatigue can be defined as the transient decrease in maximal force that occurs in response to muscle use. Fatigue develops because of a complex set of changes within the neuromuscular system that are difficult to evaluate simultaneously in humans. The skeletal muscle of older adults fatigues less than that of young adults during static contractions. The potential sources of this difference are multiple and intertwined. To evaluate the individual mechanisms of fatigue, we developed an integrative computational model based on neural, biochemical, morphological and physiological properties of human skeletal muscle. Our results indicate first that the model provides accurate predictions of fatigue and second that the age-related resistance to fatigue is due largely to a lower reliance on glycolytic metabolism during contraction. This model should prove useful for generating hypotheses for future experimental studies into the mechanisms of muscle fatigue. ABSTRACT: During repeated or sustained muscle activation, force-generating capacity becomes limited in a process referred to as fatigue. Multiple factors, including motor unit activation patterns, muscle fibre contractile properties and bioenergetic function, can impact force-generating capacity and thus the potential to resist fatigue. Given that neuromuscular fatigue depends on interrelated factors, quantifying their independent effects on force-generating capacity is not possible in vivo. Computational models can provide insight into complex systems in which multiple inputs determine discrete outputs. However, few computational models to date have investigated neuromuscular fatigue by incorporating the multiple levels of neuromuscular function known to impact human in vivo function. To address this limitation, we present a computational model that predicts neural activation, biomechanical forces, intracellular metabolic perturbations and, ultimately, fatigue during repeated isometric contractions. This model was compared with metabolic and contractile responses to repeated activation using values reported in the literature. Once validated in this way, the model was modified to reflect age-related changes in neuromuscular function. Comparisons between initial and age-modified simulations indicated that the age-modified model predicted less fatigue during repeated isometric contractions, consistent with reports in the literature. Together, our simulations suggest that reduced glycolytic flux is the greatest contributor to the phenomenon of age-related fatigue resistance. In contrast, oxidative resynthesis of phosphocreatine between intermittent contractions and inherent buffering capacity had minimal impact on predicted fatigue during isometric contractions. The insights gained from these simulations cannot be achieved through traditional in vivo or in vitro experimentation alone. PMID- 26824935 TI - Antibody Detection and Molecular Characterization of Toxoplasma gondii from Bobcats (Lynx rufus), Domestic Cats (Felis catus), and Wildlife from Minnesota, USA. AB - Little is known of the epidemiology of toxoplasmosis in Minnesota. Here, we evaluated Toxoplasma gondii infection in 50 wild bobcats (Lynx rufus) and 75 other animals on/near 10 cattle farms. Antibodies to T. gondii were assayed in serum samples or tissue fluids by the modified agglutination test (MAT, cut-off 1:25). Twenty nine of 50 bobcats and 15 of 41 wildlife trapped on the vicinity of 10 farms and nine of 16 adult domestic cats (Felis catus) and six of 14 domestic dogs resident on farms were seropositive. Toxoplasma gondii oocysts were not found in feces of any felid. Tissues of all seropositive wild animals trapped on the farm were bioassayed in mice and viable T. gondii was isolated from two badgers (Taxidea taxus), two raccoons (Procyon lotor), one coyote (Canis latrans), and one opossum (Didelphis virginiana). All six T. gondii isolates were further propagated in cell culture. Multi-locus PCR-RFLP genotyping using 10 markers (SAG1, SAG2 (5'-3'SAG2, and alt.SAG2), SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico), and DNA from cell culture derived tachyzoites revealed three genotypes; #5 ToxoDataBase (1 coyote, 1 raccoon), #1 (1 badger, 1 raccoon, 1 opossum), and #2 (1 badger). This is the first report of T. gondii prevalence in domestic cats and in bobcats from Minnesota, and the first isolation of viable T. gondii from badger. PMID- 26824936 TI - Killing of Trypanozoon Parasites by the Equine Cathelicidin eCATH1. AB - Trypanozoon parasites infect both humans, causing sleeping sickness, and animals, causing nagana, surra, and dourine. Control of nagana and surra depends to a great extent on chemotherapy. However, drug resistance to several of the front line drugs is rising. Furthermore, there is no official treatment for dourine. Therefore, there is an urgent need to develop antiparasitic agents with novel modes of action. Host defense peptides have recently gained attention as promising candidates. We have previously reported that one such peptide, the equine antimicrobial peptide eCATH1, is highly active against equine Gram positive and Gram-negative bacteria, without cytotoxicity against mammalian cells at bacteriolytic concentrations. In the present study, we show that eCATH1 exhibits an in vitro 50% inhibitory concentration (IC50) of 9.5 MUM against Trypanosoma brucei brucei, Trypanosoma evansi, and Trypanosoma equiperdum Its trypanocidal mechanism involves plasma membrane permeabilization and mitochondrial alteration based on the following data: (i) eCATH1 induces the rapid influx of the vital dye SYTOX Green; (ii) it rapidly disrupts mitochondrial membrane potential, as revealed by immunofluorescence microscopy using the fluorescent dye rhodamine 123; (iii) it severely damages the membrane and intracellular structures of the parasites as early as 15 min after exposure at 9.5 MUM and 5 min after exposure at higher concentrations (19 MUM), as evidenced by scanning and transmission electron microscopy. We also demonstrate that administration of eCATH1 at a dose of 10 mg/kg to T. equiperdum-infected mice delays mortality. Taken together, our findings suggest that eCATH1 is an interesting template for the development of novel therapeutic agents in the treatment of trypanosome infections. PMID- 26824937 TI - Mutational Analysis of Quinolone Resistance Protein QnrVC7 Provides Novel Insights into the Structure-Activity Relationship of Qnr Proteins. AB - This study assessed the functional importance of residues located at the i(-2) position of face 4 of the tandem repeat loops of the quinolone resistance protein QnrVC7 through mutagenesis studies. The i(-2) position of face 4 on different coils required residues with different natures. Some substitutions reduced the protective activity of QnrVC7, while some of them increased it. These findings advanced our understanding on the detailed structural organization and functional requirements of Qnr proteins. PMID- 26824938 TI - Aminophthalocyanine-Mediated Photodynamic Inactivation of Leishmania tropica. AB - Photodynamic inactivation ofLeishmaniaspp. requires the cellular uptake of photosensitizers, e.g., endocytosis of silicon(IV)-phthalocyanines (PC) axially substituted with bulky ligands. We report here that when substituted with amino containing ligands, the PCs (PC1 and PC2) were endocytosed and displayed improved potency againstLeishmania tropicapromastigotes and axenic amastigotesin vitro The uptake of these PCs by bothLeishmaniastages followed saturation kinetics, as expected. Sensitive assays were developed for assessing the photodynamic inactivation ofLeishmaniaspp. by rendering them fluorescent in two ways: transfecting promastigotes to express green fluorescent protein (GFP) and loading them with carboxyfluorescein succinimidyl ester (CFSE). PC-sensitizedLeishmania tropicastrains were seen microscopically to lose their motility, structural integrity, and GFP/CFSE fluorescence after exposure to red light (wavelength, ~650 nm) at a fluence of 1 to 2 J cm(-2) Quantitative fluorescence assays based on the loss of GFP/CFSE from liveLeishmania tropicashowed that PC1 and PC2 dose dependently sensitized both stages for photoinactivation, consistent with the results of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay.Leishmania tropicastrains are >100 times more sensitive than their host cells or macrophages to PC1- and PC2-mediated photoinactivation, judging from the estimated 50% effective concentrations (EC50s) of these cells. Axial substitution of the PC with amino groups instead of other ligands appears to increase its leishmanial photolytic activity by up to 40-fold. PC1 and PC2 are thus potentially useful for photodynamic therapy of leishmaniasis and for oxidative photoinactivation ofLeishmaniaspp. for use as vaccines or vaccine carriers. PMID- 26824939 TI - Novel Piperazine Arylideneimidazolones Inhibit the AcrAB-TolC Pump in Escherichia coli and Simultaneously Act as Fluorescent Membrane Probes in a Combined Real Time Influx and Efflux Assay. AB - In this study, we tested five compounds belonging to a novel series of piperazine arylideneimidazolones for the ability to inhibit the AcrAB-TolC efflux pump. The biphenylmethylene derivative (BM-19) and the fluorenylmethylene derivative (BM 38) were found to possess the strongest efflux pump inhibitor (EPI) activities in the AcrAB-TolC-overproducingEscherichia colistrain 3-AG100, whereas BM-9, BM-27, and BM-36 had no activity at concentrations of up to 50 MUM in a Nile red efflux assay. MIC microdilution assays demonstrated that BM-19 at 1/4 MIC (intrinsic MIC, 200 MUM) was able to reduce the MICs of levofloxacin, oxacillin, linezolid, and clarithromycin 8-fold. BM-38 at 1/4 MIC (intrinsic MIC, 100 MUM) was able to reduce only the MICs of oxacillin and linezolid (2-fold). Both compounds markedly reduced the MIC of rifampin (BM-19, 32-fold; and BM-38, 4-fold), which is suggestive of permeabilization of the outer membrane as an additional mechanism of action. Nitrocefin hydrolysis assays demonstrated that in addition to their EPI activity, both compounds were in fact weak permeabilizers of the outer membrane. Moreover, it was found that BM-19, BM-27, BM-36, and BM-38 acted as near-infrared-emitting fluorescent membrane probes, which allowed for their use in a combined influx and efflux assay and thus for tracking of the transport of an EPI across the outer membrane by an efflux pump in real time. The EPIs BM-38 and BM-19 displayed the most rapid influx of all compounds, whereas BM-27, which did not act as an EPI, showed the slowest influx. PMID- 26824941 TI - Toward an Evidence-Based Nonclinical Road Map for Evaluating the Efficacy of New Tuberculosis (TB) Drug Regimens: Proceedings of a Critical Path to TB Drug Regimens-National Institute of Allergy and Infectious Diseases In Vivo Pharmacology Workshop for TB Drug Development. AB - Novel tuberculosis (TB) drug regimens are urgently needed, and their development will be enabled by improved preclinical approaches that more effectively inform and ensure safe selection of clinical candidates and drug combination/regimens. An evidence-based approach for the assessment of nonclinical models supporting TB drug development has been proposed by a joint partnership between the National Institute of Allergy and Infectious Diseases (NIAID) and the Critical Path to TB Drug Regimens (CPTR) Consortium. PMID- 26824940 TI - Prospective, Controlled Study of Acyclovir Pharmacokinetics in Obese Patients. AB - The current recommendations for intravenous (i.v.) acyclovir dosing in obese patients suggest using ideal body weight (IBW) rather than total body weight (TBW). To our knowledge, no pharmacokinetic analysis has validated this recommendation. This single-dose pharmacokinetic study was conducted in an inpatient oncology population. Enrollment was conducted by 1:1 matching of obese patients (>190% of IBW) to normal-weight patients (80 to 120% of IBW). All patients received a single dose of i.v. acyclovir, 5 mg/kg, infused over 60 min. Consistent with current recommendations, IBW was used for obese patients and TBW for normal-weight patients. Serial plasma concentrations were obtained and compared. Seven obese and seven normal-weight patients were enrolled, with mean body mass indexes of 45.0 and 22.5 kg/m(2), respectively. Systemic clearance was substantially higher in the obese than normal-weight patients (mean, 19.4 +/- 5.3 versus 14.3 +/- 5.4 liters/h; P = 0.047). Area under the concentration-time curve was lower in the obese patients (15.2 +/- 2.9 versus 24.0 +/- 9.4 mg . h/liter; P = 0.011), as was maximum concentration (5.8 +/- 0.9 versus 8.2 +/- 1.3 mg/liter; P = 0.031). Utilization of IBW for dose calculation of i.v. acyclovir in obese patients leads to lower systemic exposure than dosing by TBW in normal-weight patients. While not directly evaluated in this study, utilization of an adjusted body weight for dose determination appears to more closely approximate the exposure seen in normal-weight patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01714180.). PMID- 26824942 TI - Contribution of Population Pharmacokinetics to Dose Optimization of Ganciclovir Valganciclovir in Solid-Organ Transplant Patients. AB - Treatment of solid-organ transplant (SOT) patients with ganciclovir (GCV) valganciclovir (VGCV) according to the manufacturer's recommendations may result in over- or underexposure. Bayesian prediction based on a population pharmacokinetics model may optimize GCV-VGCV dosing, achieving the area under the curve (AUC) therapeutic target. We conducted a two-arm, randomized, open-label, 40% superiority trial in adult SOT patients receiving GCV-VGCV as prophylaxis or treatment of cytomegalovirus infection. Group A was treated according to the manufacturer's recommendations. For group B, the dosing was adjusted based on target exposures using a Bayesian prediction model (NONMEM). Fifty-three patients were recruited (27 in group A and 26 in group B). About 88.6% of patients in group B and 22.2% in group A reached target AUC, achieving the 40% superiority margin (P< 0.001; 95% confidence interval [CI] difference, 47 to 86%). The time to reach target AUC was significantly longer in group A than in group B (55.9 +/- 8.2 versus 15.8 +/- 2.3 days,P< 0.001). A shorter time to viral clearance was observed in group B than in group A (12.5 versus 17.6 days;P= 0.125). The incidences of relapse (group A, 66.67%, and group B, 9.01%) and late-onset infection (group A, 36.7%, and group B, 7.7%) were higher in group A. Neutropenia and anemia were related to GCV overexposure. GCV-VCGV dose adjustment based on a population pharmacokinetics Bayesian prediction model optimizes GCV-VGCV exposure. (This study has been registered at ClinicalTrials.gov under registration no. NCT01446445.). PMID- 26824943 TI - Novel Aminoglycoside Resistance Transposons and Transposon-Derived Circular Forms Detected in Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates. AB - Acinetobacter baumannii has emerged as an important opportunistic pathogen equipped with a growing number of antibiotic resistance genes. Our study investigated the molecular epidemiology and antibiotic resistance features of 28 consecutive carbapenem-resistant clinical isolates of A. baumannii collected throughout Sweden in 2012 and 2013. The isolates mainly belonged to clonal complexes (CCs) with an extensive international distribution, such as CC2 (n = 16) and CC25 (n = 7). Resistance to carbapenems was related to blaOXA-23 (20 isolates), blaOXA-24/40-like (6 isolates), blaOXA-467 (1 isolate), and ISAba1 blaOXA-69 (1 isolate). Ceftazidime resistance was associated with blaPER-7 in the CC25 isolates. Two classical point mutations were responsible for resistance to quinolones in all the isolates. Isolates with high levels of resistance to aminoglycosides carried the 16S rRNA methylase armA gene. The isolates also carried a variety of genes encoding aminoglycoside-modifying enzymes. Several novel structures involved in aminoglycoside resistance were identified, including Tn6279, DeltaTn6279, Ab-ST3-aadB, and different assemblies of Tn6020 and TnaphA6. Importantly, a number of circular forms related to the IS26 or ISAba125 composite transposons were detected. The frequent occurrence of these circular forms in the populations of several isolates indicates a potential role of these circular forms in the dissemination of antibiotic resistance genes. PMID- 26824944 TI - Destabilization of alpha-Helical Structure in Solution Improves Bactericidal Activity of Antimicrobial Peptides: Opposite Effects on Bacterial and Viral Targets. AB - We have previously examined the mechanism of antimicrobial peptides on the outer membrane of vaccinia virus. We show here that the formulation of peptides LL37 and magainin-2B amide in polysorbate 20 (Tween 20) results in greater reductions in virus titer than formulation without detergent, and the effect is replicated by substitution of polysorbate 20 with high-ionic-strength buffer. In contrast, formulation with polysorbate 20 or high-ionic-strength buffer has the opposite effect on bactericidal activity of both peptides, resulting in lesser reductions in titer for both Gram-positive and Gram-negative bacteria. Circular dichroism spectroscopy shows that the differential action of polysorbate 20 and salt on the virucidal and bactericidal activities correlates with the alpha-helical content of peptide secondary structure in solution, suggesting that the virucidal and bactericidal activities are mediated through distinct mechanisms. The correlation of a defined structural feature with differential activity against a host-derived viral membrane and the membranes of both Gram-positive and Gram-negative bacteria suggests that the overall helical content in solution under physiological conditions is an important feature for consideration in the design and development of candidate peptide-based antimicrobial compounds. PMID- 26824946 TI - Is Aerosolized Pentamidine for Pneumocystis Pneumonia Prophylaxis in Renal Transplant Recipients Not as Safe as We Might Think? AB - Outbreaks ofPneumocystispneumonia have been described in renal transplant recipients. Aerosolized pentamidine is frequently used for prophylaxis in this setting. We report our experience with aerosolized pentamidine use in 56 renal transplant recipients. We found high rates of adverse reactions in patients with chronic respiratory disease. PMID- 26824945 TI - Nitazoxanide Inhibits Pilus Biogenesis by Interfering with Folding of the Usher Protein in the Outer Membrane. AB - Many bacterial pathogens assemble surface fibers termed pili or fimbriae that facilitate attachment to host cells and colonization of host tissues. The chaperone/usher (CU) pathway is a conserved secretion system that is responsible for the assembly of virulence-associated pili by many different Gram-negative bacteria. Pilus biogenesis by the CU pathway requires a dedicated periplasmic chaperone and an integral outer membrane (OM) assembly and secretion platform termed the usher. Nitazoxanide (NTZ), an antiparasitic drug, was previously shown to inhibit the function of aggregative adherence fimbriae and type 1 pili assembled by the CU pathway in enteroaggregativeEscherichia coli, an important causative agent of diarrhea. We show here that NTZ also inhibits the function of type 1 and P pili from uropathogenicE. coli(UPEC). UPEC is the primary causative agent of urinary tract infections, and type 1 and P pili mediate colonization of the bladder and kidneys, respectively. By analysis of the different stages of the CU pilus biogenesis pathway, we show that treatment of bacteria with NTZ causes a reduction in the number of usher molecules in the OM, resulting in a loss of pilus assembly on the bacterial surface. In addition, we determine that NTZ specifically prevents proper folding of the usher beta-barrel domain in the OM. Our findings demonstrate that NTZ is a pilicide with a novel mechanism of action and activity against diverse CU pathways. This suggests that further development of the NTZ scaffold may lead to new antivirulence agents that target the usher to prevent pilus assembly. PMID- 26824947 TI - Survey of Carbapenemase-Producing Enterobacteriaceae in Companion Dogs in Madrid, Spain. AB - We found a low prevalence (0.6%) of carbapenemase producingEnterobacteriaceae(CPE) in fecal microbiota of companion dogs. A single VIM-1-producingKlebsiella pneumoniaeisolate belonging to sequence type (ST) 2090 was detected.blaVIM-1was carried on a class 1 integron and an untypeable ~48-kb plasmid. Emergence and spread of CPE in this group of animals may be a threat to public health in human and veterinary medicine. This finding supports the need for active surveillance studies in companion animals that live close to humans, as interspecies transmission may occur within the same household. PMID- 26824948 TI - Inhibition of Hippocampal Regeneration by Adjuvant Dexamethasone in Experimental Infant Rat Pneumococcal Meningitis. AB - Pneumococcal meningitis (PM) causes neurological sequelae in up to half of surviving patients. Neuronal damage associated with poor outcome is largely mediated by the inflammatory host response. Dexamethasone (DXM) is used as an adjuvant therapy in adult PM, but its efficacy in the treatment of pneumococcal meningitis in children is controversially discussed. While DXM has previously been shown to enhance hippocampal apoptosis in experimental PM, its impact on hippocampal cell proliferation is not known. This study investigated the impact of DXM on hippocampal proliferation in infant rat PM. Eleven-day-old nursing Wistar rats (n = 90) were intracisternally infected with Streptococcus pneumoniae to induce experimental meningitis. Treatment with DXM or vehicle was started 18 h after infection, concomitantly with antibiotics (ceftriaxone 100 mg/kg of body weight twice a day [b.i.d.]). Clinical parameters were monitored, and the amount of cells with proliferating activity was assessed using in vivo incorporation of bromodeoxyuridine (BrdU) and an in vitro neurosphere culture system at 3 and 4 d postinfection. DXM significantly worsened weight loss and survival. Density of BrdU-positive cells, as an index of cells with proliferating activity, was significantly lower in DXM-treated animals compared to vehicle controls (P < 0.0001). In parallel, DXM reduced neurosphere formation as an index for stem/progenitor cell density compared to vehicle treatment (P = 0.01). Our findings provide clear evidence that DXM exerts an antiproliferative effect on the hippocampus in infant rat PM. We conclude that an impairment of regenerative hippocampal capacity should be taken into account when considering adjuvant DXM in the therapeutic regimen for PM in children. PMID- 26824949 TI - A Complex Network of Interactions between S282 and G283 of Hepatitis C Virus Nonstructural Protein 5B and the Template Strand Affects Susceptibility to Sofosbuvir and Ribavirin. AB - The hepatitis C virus (HCV) RNA-dependent RNA-polymerase NS5B is essentially required for viral replication and serves as a prominent drug target. Sofosbuvir is a prodrug of a nucleotide analog that interacts selectively with NS5B and has been approved for HCV treatment in combination with ribavirin. Although the emergence of resistance to sofosbuvir is rarely seen in the clinic, the S282T mutation was shown to decrease susceptibility to this drug. S282T was also shown to confer hypersusceptibility to ribavirin, which is of potential clinical benefit. Here we devised a biochemical approach to elucidate the underlying mechanisms. Recent crystallographic data revealed a hydrogen bond between S282 and the 2'-hydroxyl of the bound nucleotide, while the adjacent G283 forms a hydrogen bond with the 2'-hydroxyl of the residue of the template that base pairs with the nucleotide substrate. We show that DNA-like modifications of the template that disrupt hydrogen bonding with G283 cause enzyme pausing with natural nucleotides. However, the specifically introduced DNA residue of the template reestablishes binding and incorporation of sofosbuvir in the context of S282T. Moreover, the DNA-like modifications of the template prevent the incorporation of ribavirin in the context of the wild-type enzyme, whereas the S282T mutant enables the binding and incorporation of ribavirin under the same conditions. Together, these findings provide strong evidence to show that susceptibility to sofosbuvir and ribavirin depends crucially on a network of interdependent hydrogen bonds that involve the adjacent residues S282 and G283 and their interactions with the incoming nucleotide and complementary template residue, respectively. PMID- 26824950 TI - In Vitro Antiviral Activity and Resistance Profile Characterization of the Hepatitis C Virus NS5A Inhibitor Ledipasvir. AB - Ledipasvir (LDV; GS-5885), a component of Harvoni (a fixed-dose combination of LDV with sofosbuvir [SOF]), is approved to treat chronic hepatitis C virus (HCV) infection. Here, we report key preclinical antiviral properties of LDV, including in vitro potency, in vitro resistance profile, and activity in combination with other anti-HCV agents. LDV has picomolar antiviral activity against genotype 1a and genotype 1b replicons with 50% effective concentration (EC50) values of 0.031 nM and 0.004 nM, respectively. LDV is also active against HCV genotypes 4a, 4d, 5a, and 6a with EC50 values of 0.11 to 1.1 nM. LDV has relatively less in vitro antiviral activity against genotypes 2a, 2b, 3a, and 6e, with EC50 values of 16 to 530 nM. In vitro resistance selection with LDV identified the single Y93H and Q30E resistance-associated variants (RAVs) in the NS5A gene; these RAVs were also observed in patients after a 3-day monotherapy treatment. In vitro antiviral combination studies indicate that LDV has additive to moderately synergistic antiviral activity when combined with other classes of HCV direct-acting antiviral (DAA) agents, including NS3/4A protease inhibitors and the nucleotide NS5B polymerase inhibitor SOF. Furthermore, LDV is active against known NS3 protease and NS5B polymerase inhibitor RAVs with EC50 values equivalent to those for the wild type. PMID- 26824951 TI - Colistin-Nonsusceptible Pseudomonas aeruginosa Sequence Type 654 with blaNDM-1 Arrives in North America. AB - This study describes 3 different blaNDM-1 genetic platforms in 3 different species obtained from the same patient who was directly transferred to an institution in Calgary, Alberta, Canada, following a prolonged hospital stay in India. The blaNDM-1 in the Escherichia coli isolate was located on a 176-kb IncA/C plasmid contained within an ISCR1 region. The blaNDM-1 in the Providencia rettgeri isolate was located on a 117-kb IncT plasmid contained within Tn3000, while the blaNDM-1 in the Pseudomonas aeruginosa isolate was located on the chromosome within an ISCR3 region. This report highlights the plasticity of the genetic regions and environments associated with blaNDM-1. To the best of our knowledge, this is the first report of P. aeruginosa with blaNDM-1 identified in North America and the first report of blaOXA-181 in P. rettgeri. The P. aeruginosa isolate belonged to the international high-risk sequence type 654 clone and was nonsusceptible to colistin. This case emphasizes the need for the use of appropriate infection prevention and control measures and vigilant screening for carbapenem-resistant Gram-negative bacteria in patients with a history of travel to areas of endemicity, such as the Indian subcontinent. PMID- 26824952 TI - Incidence and Risk Factors of Ocular Infection Caused by Staphylococcus aureus Bacteremia. AB - Staphylococcus aureusbacteremia (SAB) often leads to ocular infections, including endophthalmitis and chorioretinitis. However, the incidence, risk factors, and outcomes of ocular infections complicated by SAB are largely unknown. We retrospectively analyzed the incidence and risk factors of ocular involvement in a prospective cohort of patients with SAB at a tertiary-care hospital. Ophthalmologists reviewed the fundoscopic findings and classified the ocular infections as endophthalmitis or chorioretinitis. During the 5-year study period, 1,109 patients had SAB, and data for 612 (55%) who underwent ophthalmic examinations within 14 days after SAB onset were analyzed. Of those 612 patients, 56 (9% [95% confidence interval [CI], 7 to 12%]) had ocular involvement, including 15 (2.5%) with endophthalmitis and 41 (6.7%) with chorioretinitis. In a multivariate analysis, infective endocarditis (adjusted odds ratio [aOR], 5.74 [95% CI, 2.25 to 14.64]) and metastatic infection (aOR, 2.38 [95% CI, 1.29 to 4.39]) were independent risk factors for ocular involvement. Of the 47 patients with ocular involvement who could communicate, only 17 (36%) had visual disturbances. Two-thirds of the patients with endophthalmitis (10/15 patients) were treated with intravitreal antibiotics combined with parenteral antibiotics, whereas all of the patients with chorioretinitis were treated only with systemic antibiotics. No patients became blind. Among 42 patients for whom follow-up assessments were available, the ocular lesions improved in 29 (69%) but remained the same in the others. Ocular involvement was independently associated with death within 30 days after SAB onset. Ocular involvement is not uncommon among patients with SAB. Routine ophthalmic examinations should be considered for patients with infective endocarditis or metastatic infections caused by SAB. PMID- 26824953 TI - blaNDM-5-Bearing IncFII-Type Plasmids of Klebsiella pneumoniae Sequence Type 147 Transmitted by Cross-Border Transfer of a Patient. AB - The two plasmids extracted from Klebsiella pneumoniae sequence type 147 (ST147) isolates were analyzed. The first isolate was obtained from a patient transferred from United Arab Emirates to South Korea. The second isolate was obtained from a Korean patient and was suspected to be transmitted from the first patient. Sequences of two plasmids were almost the same, and genetic structures, including blaNDM-5, of these plasmids were similar to plasmids of NDM-1-producing Escherichia coli ST131 isolates found in Europe. PMID- 26824954 TI - Regulatory Mutations Impacting Antibiotic Susceptibility in an Established Staphylococcus aureus Biofilm. AB - We previously determined the extent to which mutations of different Staphylococcus aureus regulatory loci impact biofilm formation as assessed under in vitro conditions. Here we extend these studies to determine the extent to which those regulatory loci that had the greatest effect on biofilm formation also impact antibiotic susceptibility. The experiments were done under in vitro and in vivo conditions using two clinical isolates of S. aureus (LAC and UAMS-1) and two functionally diverse antibiotics (daptomycin and ceftaroline). Mutation of the staphylococcal accessory regulator (sarA) or sigB was found to significantly increase susceptibilities to both antibiotics and in both strains in a manner that could not be explained by changes in the MICs. The impact of a mutation in sarA was comparable to that of a mutation in sigB and greater than the impact observed with any other mutant. These results suggest that therapeutic strategies targeting sarA and/or sigB have the greatest potential to facilitate the ability to overcome the intrinsic antibiotic resistance that defines S. aureus biofilm-associated infections. PMID- 26824955 TI - First Characterization of CTX-M-15-Producing Escherichia coli Strains Belonging to Sequence Type (ST) 410, ST224, and ST1284 from Commercial Swine in South America. AB - We report for the first time the isolation of CTX-M-15-producingEscherichia colistrains belonging to sequence type (ST) 410, ST224, and ST1284 in commercial swine in Brazil. TheblaCTX-M-15gene was located on F-::A9::B1 and C1::A9::B1 IncF type plasmids, surrounded by a new genetic context comprising the IS26insertion sequence truncated with the ISEcp1element upstream ofblaCTX-M-15 These results reveal that commercial swine have become a new reservoir of CTX-M-15-producing bacteria in South America. PMID- 26824956 TI - Characterization of VCC-1, a Novel Ambler Class A Carbapenemase from Vibrio cholerae Isolated from Imported Retail Shrimp Sold in Canada. AB - One of the core goals of the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) is to monitor major meat commodities for antimicrobial resistance. Targeted studies with methodologies based on core surveillance protocols are used to examine other foods, e.g., seafood, for antimicrobial resistance to detect resistances of concern to public health. Here we report the discovery of a novel Ambler class A carbapenemase that was identified in a nontoxigenic strain of Vibrio cholerae (N14-02106) isolated from shrimp that was sold for human consumption in Canada. V. cholerae N14-02106 was resistant to penicillins, carbapenems, and monobactam antibiotics; however, PCR did not detect common beta-lactamases. Bioinformatic analysis of the whole-genome sequence of V. cholerae N14-02106 revealed on the large chromosome a novel carbapenemase (referred to here as VCC-1, for Vibrio cholerae carbapenemase 1) with sequence similarity to class A enzymes. Two copies of blaVCC-1 separated and flanked by ISVch9 (i.e., 3 copies of ISVch9) were found in an acquired 8.5-kb region inserted into a VrgG family protein gene. Cloned blaVCC-1 conferred a beta lactam resistance profile similar to that in V. cholerae N14-02106 when it was transformed into a susceptible laboratory strain of Escherichia coli. Purified VCC-1 was found to hydrolyze penicillins, 1st-generation cephalosporins, aztreonam, and carbapenems, whereas 2nd- and 3rd-generation cephalosporins were poor substrates. Using nitrocefin as a reporter substrate, VCC-1 was moderately inhibited by clavulanic acid and tazobactam but not EDTA. In this report, we present the discovery of a novel class A carbapenemase from the food supply. PMID- 26824957 TI - Characterization of SXT/R391 Integrative and Conjugative Elements in Proteus mirabilis Isolates from Food-Producing Animals in China. AB - SXT/R391 integrative and conjugative elements (ICEs) were detected in 8 out of 125 Proteus mirabilis isolates from food-producing animals in China. Whole-genome sequencing revealed that seven ICEs were identical to ICEPmiJpn1, carrying the cephalosporinase gene blaCMY-2. Another one, designated ICEPmiChn1, carried five resistance genes. All eight ICEs could be transferred to Escherichia coli via conjugation. The results highlight the idea that animal farms are important reservoir of the SXT/R391 ICE-containing P. mirabilis. PMID- 26824958 TI - Natural History of Francisella tularensis in Aerosol-Challenged BALB/c Mice. AB - The objective of this study was to evaluate the natural history and pathogenesis of Francisella tularensis in a murine model of inhalational tularemia with the SchuS4 strain. Before the efficacy of antimicrobials could be assessed in this model, further model development was required to determine the optimal time to start therapy. This study helped define the time course of infection after aerosol challenge by quantifying the presence of bacteria in lung, blood, and spleen at multiple harvest points. In this study, mice were infected via a targeted inhaled dose of 100 50% lethal doses (LD50s) (LD50 = 300 CFU) of F. tularensis by whole-body aerosol. At 1, 24, 36, 48, 60, 72, 75, 78, 81, 84, 87, and 90 h postchallenge, groups of 15 animals were sacrificed and blood, lung, and splenic tissue samples were harvested, homogenized, plated, and incubated to evaluate the bacterial load in those tissues. It was determined that of the 3 sample types harvested, splenic tissue provided the most consistent bacterial counts, which steadily increased with the progressing infection. Further, it was determined that lung samples from all (15/15) animals were positive for infection at 75 h postaerosolization and that 14/15 animals had positive splenic tissue counts. Bacterial levels in blood were not predictive of treatment initiation. For future therapeutic evaluation studies in this model using F. tularensis (SchuS4), it was determined that therapy should be initiated at 75 h postchallenge and validated by spleen involvement. PMID- 26824959 TI - Colistin Resistance Caused by Inactivation of the MgrB Regulator Is Not Associated with Decreased Virulence of Sequence Type 258 KPC Carbapenemase Producing Klebsiella pneumoniae. AB - Using aGalleria mellonellaanimal model, we compared the virulence of two sequence type 258 (ST258) KPC-producingKlebsiella pneumoniaestrains, which were representative of the two clades of this clonal lineage, with that of isogenic colistin-resistantmgrBmutants. With both strains, themgrBmutants did not exhibit modification in virulence. In theG. mellonellamodel, the clade 1 strain (capsular typecps-1[wzi29, producing KPC-2]) was significantly more virulent than the clade 2 strain (capsular typecps-2[wzi154, producing KPC-3]). PMID- 26824960 TI - Highly Drug-Resistant Salmonella enterica Serovar Indiana Clinical Isolates Recovered from Broilers and Poultry Workers with Diarrhea in China. AB - Highly drug-resistant Salmonella enterica serovar Indiana became the most common serovar in broilers with diarrhea in China over the course of this study (15% in 2010 to 70% in 2014). While most S. Indiana isolates (87%, 384/440) were resistant to 13 to 16 of the 16 antibiotics tested, 89% of non-S. Indiana isolates (528/595) were resistant to 0 to 6 antibiotics. Class 1 integrons and IncHI2-type plasmids were detected in all S. Indiana isolates, but only in 39% and 1% of non-S. Indiana isolates. PMID- 26824961 TI - Enhanced Bioaccessibility of Curcuminoids in Buttermilk Yogurt in Comparison to Curcuminoids in Aqueous Dispersions. AB - Curcuminoids have low bioavailability due to low aqueous solubility. We compared the bioaccessibility of curcuminoids delivered in buttermilk yogurt to that of curcuminoid powder in an aqueous dispersion. Buttermilk containing added curcuminoids (300 mg/100 g, 0.3% w/w) was used for yogurt manufacture. We measured percentage of curcuminoids remaining in yogurts after manufacture and after exposure to simulated gastrointestinal fluids, and the in vitro bioaccessibility of the curcuminoids. Curcuminoids were stable during yogurt manufacture. At the end of in vitro digestion, approximately 11% of the curcuminoids delivered in yogurt was degraded compared to <1% for curcuminoids in an aqueous dispersion. However, curcuminoids delivered in yogurt was 15-fold more bioaccessible than curcuminoids in aqueous dispersion. The small change in yogurt properties (decrease in total lactic acid bacteria counts of <1 log and increased viscosity) on addition of curcuminoids has to be balanced against the benefits of increased bioaccessibility of curcuminoids when delivered in yogurts. PMID- 26824963 TI - Population Care Management and Team-Based Approach to Reduce Racial Disparities among African Americans/Blacks with Hypertension. AB - OBJECTIVES: At Kaiser Permanente, national Equitable Care Health Outcomes (ECHO) Reports with a baseline measurement of 16 Healthcare Effectiveness Data and Information Set measures stratified by race and ethnicity showed a disparity of 8.1 percentage points in blood pressure (BP) control rates between African- American/black (black) and white members. The aims of this study were to describe a population care management team-based approach to improve BP control for large populations and to explain how a culturally tailored, patient-centered approach can address this racial disparity. METHODS: These strategies were implemented through: 1) physician-led educational programs on treatment intensification, medication adherence, and consistent use of clinical practice guidelines; 2) building strong care teams by defining individual roles and responsibilities in hypertension management; 3) redesign of the care delivery system to expand access; and 4) programs on culturally tailored communication tools and self management. RESULTS: At a physician practice level where 65% of patients with hypertension were black, BP control rates (< 140/90 mmHg) for blacks improved from 76.6% to 81.4%, and control rates for whites increased from 82.9% to 84.2%. The racial gap narrowed from 6.3% to 2.8%. As these successful practices continue to spread throughout the program, the health disparity gap in BP control has decreased by 50%, from 8.1% to 3.9%. CONCLUSION: A sustainable program to collect self-reported race, ethnicity, and language preference data integrated with successful population care management programs provided the foundation for addressing health disparities. Cultural tailoring of a multilevel team-based approach closed the gap for blacks with hypertension. PMID- 26824964 TI - Are Men at High Risk for Osteoporosis Underscreened? A Quality Improvement Project. AB - CONTEXT: Osteoporosis is a major cause of morbidity and mortality in both men and women. The mortality rate in men within 1 year of hip fracture is 37.5%, which is 51% higher than in women. Although clear guidelines exist for osteoporosis screening in women, these are less clear for men. The available guidelines recommend screening high-risk men; however, screening does not appear to be a standard practice. OBJECTIVE: To increase screening rates of osteoporosis in high risk men in our primary care clinic by 50%. DESIGN: The screening rate of osteoporosis was determined in high-risk male veterans more than 50 years of age enrolled in the resident physician- and nurse practitioner-staffed primary care clinics at a Veterans Affairs Medical Center in Cleveland, OH. High-risk factors included prolonged use of steroids; hypogonadism; and autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus, which are known to be associated with osteoporosis. We surveyed health care professional trainees and nurses to explore their barriers to screening for osteoporosis in high-risk men. MAIN OUTCOME MEASURES: After creating awareness about the importance of this condition among the health care professionals, we analyzed whether this education had any impact on the screening rate. RESULTS: The baseline screening rate in high-risk men was 11%. After phased surveys and awareness building, the screening rate increased to 20%. CONCLUSION: Osteoporosis in high-risk men is under-screened. Creating more awareness about the impact of this condition among health professional trainees and nurses can lead to improved screening rates. PMID- 26824962 TI - Early Hospital Readmission and Mortality Risk after Surgical Treatment of Proximal Humerus Fractures in a Community-Based Health Care Organization. AB - CONTEXT: Surgical treatment for proximal humerus fractures has increased exponentially. Recent health care policies incentivize centers to reduce hospital readmission rates. Better understanding of risk factors for readmission and early mortality in this population will assist in identifying favorable risk-benefit patient profiles. OBJECTIVE: To identify incidence and risk factors of 30-day hospital readmission rate and 1-year mortality rate after open surgery of proximal humerus fractures. DESIGN: Retrospective cohort analysis from Kaiser Permanente Southern California Region database. METHODS: Using International Classification of Diseases, Ninth Revision, diagnosis and procedure codes, all operative proximal humerus fractures were validated. Hospital readmission, one year mortality, and demographic and medical data were collected. A logistic regression test was performed to assess potential risk factors for outcomes. RESULTS: From 1387 surgical patients, the 30-day all-cause readmission rate was 5.6%. Forty percent of hospital read-missions were due to surgery-related reasons. Severe liver disease (odds ratio [OR], 3.48, 95% confidence interval [CI] = 1.42-8.55) and LACE (length of stay, acuity of admission, comorbidities, and number of Emergency Department visits in the previous 6 months) index score >= 10 (OR, 4.47, 95% CI = 2.54-7.86) were independent risk factors of readmission on multivariate analysis. The 1-year mortality rate was 4.86%. Multivariate analysis showed length of hospital stay (OR 1.11, 95% CI = 1.05-1.19), cancer (OR 3.38, 95% CI = 1.61-7.10), 30-day readmission (OR 3.31, 95% CI = 1.34-8.21), and Charlson comorbidity index greater than or equal to 4 (OR 13.94, 95% CI = 4.40 44.17) predicted higher mortality risk. CONCLUSION: After open treatment of proximal humerus fractures, there was a 5.6% all-cause 30-day hospital readmission rate. Surgical complications accounted for 40% of read-missions. Severe liver disease and LACE score correlated best with postoperative 30-day readmission risk. Length of hospital stay, preexisting cancer, 30-day readmission, and Charlson comorbidity index were predictive of 1-year mortality. PMID- 26824965 TI - Gingival Metastasis: A Case Report and Literature Review. AB - Secondary oral cavity neoplasms are rare. We describe a case of an indurated, nonulcerating gingival lesion in a 59-year-old nonsmoking man with no family history of lung cancer. The lesion was the presenting symptom of metastatic lung adenocarcinoma. Reviewing the literature, we find that primary lung cancer among men is one of the most common cancers to metastasize to the oral cavity. Renal and cutaneous neoplasms are the next most common neoplasms to metastasize to the oral cavity. Furthermore, the gingiva, a tissue prone to inflammation, is noted to be a common site for secondary oral cavity neoplasms. This rare case highlights that metastases should influence the clinician's differential of oral mucosal lesions. PMID- 26824966 TI - Cutaneous Metastasis of Rectal Cancer: A Case Report and Literature Review. AB - Cutaneous metastasis of rectal cancer is rare. It typically indicates widespread disease and poor prognosis. We report an exceedingly rare case of rectal cancer with metastasis to the skin and review the literature on cutaneous metastasis of rectal cancer. A 47-year-old man presented with stage IV unresectable adenocarcinoma of the rectum and received palliative chemoradiation for local pain control. About a year later he developed extensive skin lesions involving the genital area, bilateral groin, and perineum. Biopsy specimen showed mucinous adenocarcinoma compatible with rectal origin. Palliative treatment with radiation therapy was initiated. The patient responded well to treatment and is still alive more than a year after diagnosis of cutaneous metastasis. Surgeons should maintain strong suspicion of cutaneous metastases when patients with rectal cancer have new or evolving skin lesions. PMID- 26824968 TI - The Shared Context: Kaiser Permanente and the Columbia-Bassett Program. PMID- 26824967 TI - Onset of Ulcerative Colitis during a Low-Carbohydrate Weight-Loss Diet and Treatment with a Plant-Based Diet: A Case Report. AB - Overweight and obesity are global health concerns. Various effective weight-loss diets have been developed, including the Atkins diet. The Atkins diet is known as an extreme low-carbohydrate diet. This diet reduces body weight and has gained widespread popularity. However, the metabolite profiles of such a diet have been shown to be detrimental to colonic health. Therefore, a concern for the long-term health effects of this diet exists. We encountered a case in which ulcerative colitis developed while the patient was following the Atkins diet.A man, 172 cm in height and weighing 72 kg, at age 36 years followed a low-carbohydrate weight loss diet. His weight decreased to 66 kg as desired. Thereafter he noticed bloody stool. Colonoscopy revealed diffuse inflammation limited to the rectum, and he was diagnosed with ulcerative colitis. He underwent an educational hospitalization for ulcerative colitis. A plant-based/semivegetarian diet was provided during hospitalization. Bloody stool disappeared during hospitalization and he achieved remission without medication for inflammatory bowel disease.This case indicates that an onset of ulcerative colitis can be an adverse event to a low-carbohydrate weight-loss diet. PMID- 26824969 TI - Pregnancy-Associated "Cutaneous Type" Pemphigus Vulgaris. AB - The development of pemphigus, including pemphigus vulgaris (PV) and pemphigus foliaceus, during pregnancy is rare. PV manifests with mucosal and/or cutaneous erosions with flaccid bullae that are histologically characterized by suprabasilar acantholysis. In contrast, pemphigus foliaceus manifests with cutaneous-only involvement and superficial epidermal acantholysis. Enzyme-linked immunosorbent assay specific for autoantibodies against desmoglein 1 and desmoglein 3 aids in the diagnosis and differentiation between pemphigus subtypes. High-dose systemic corticosteroids are first-line agents in management of PV, yet their potential long-term use raises complex management issues associated with pregnancy and fetal risk. Here we report a rare case of cutaneous limited PV in association with pregnancy. PMID- 26824970 TI - Image Diagnosis: Immune Thrombocytopenia Secondary to Abdominal Koch Disease. PMID- 26824971 TI - Image Diagnosis: Dental and Skeletal Fluorosis. PMID- 26824972 TI - Image Diagnosis: Knee Dislocation. PMID- 26824974 TI - Biosignal processing. PMID- 26824973 TI - Five-year Follow-up and Recurrence Rates Following Surgery for Acute and Chronic Pilonidal Disease: A Survey of 421 Cases. AB - OBJECTIVE: The aim of the present study was to investigate the outcomes of different treatment options for acute and chronic pilonidal disease in a single large cohort of patients. MATERIALS AND METHODS: Four hundred and twenty-one consecutive patients (171 with chronic disease and 250 with acute abscess formation) who underwent surgery between 2003 and 2012 were included in the present study. Primary outcomes included symptomatic recurrence, time to wound healing, and time off from work. The median follow-up was 5.3 years. RESULTS: In patients with acute abscess formation, the relapse rate was significantly higher (P = 0.0001) if they were treated with abscess excision (38.9%) compared with a wide local excision (13.3%). Time to relapse was significantly longer (P = 0.0205) in patients treated with wide local excision (median 7 vs 3 months), whereas time to wound healing and the days off from work were similar among groups. In chronic disease, the relapse rate was similar in patients treated with wide local excision followed by secondary wound healing (11.3%) when compared with patients treated with limited excision (27.6%) or wide excision with primary wound closure (26.8%). The time to wound healing was shortest in patients with primary wound closure following wide local excision, and the time off from work was not significantly different between groups. CONCLUSION: Wide local excision with secondary wound healing seems to be the favorable operation method for acute and chronic pilonidal disease. PMID- 26824975 TI - Risk and protective factors for adolescent substance use: a comparative study of secondary school students in rural and urban areas of Osun State, Nigeria. AB - BACKGROUND: Substance use is a leading adolescent health problem globally, but little is known regarding associated factors for adolescent substance use in Nigeria. This study compared the prevalence of substance use among in-school adolescents in urban and rural areas of Osun State, Nigeria, and identified risk and protective factors. METHODS: This cross-sectional study involved 600 randomly selected adolescents (aged 10-19 years) from rural and urban areas of Osun State, Nigeria. Data were collected using the facilitated self-completed questionnaire method. Binary logistic regression was used to examine the association of individual, peer, and parental factors with adolescent substance use. Adjusted odds ratio (OR) and 95% confidence interval (CI) were obtained. RESULTS: About two-thirds of respondents had used substances in both rural (65.7%) and urban areas (66.0%) (p=0.93). Logistic analysis showed private school attendance as a risk factor for substance use (OR=2.32, 95% CI=1.20-4.46) and adolescent disapproval of adult substance use as a protective factor (OR=0.47, 95% CI=0.27 0.82) in rural areas. For urban areas, having friends who use substances (OR=4.04, 95% CI=1.39-11.6) and a mother having had tertiary education (OR=3.34, 95% CI=1.06-10.4) were risk factors while parental disapproval of substance use (OR=0.50, 95% CI=0.28-0.90) was a protective factor. CONCLUSION: Lifetime prevalence of substances is high among in-school adolescents in Osun State. The risk and protective factors for adolescent substance use somewhat differ for rural and urban areas, and these have implications for designing effective intervention strategies. PMID- 26824976 TI - Familial Turner syndrome: the importance of information. AB - Turner syndrome is a common genetic disorder with an incidence of 1 in 2500 live births. Spontaneous fertility is rare in such patients and is most likely in women with mosaicism or very distal Xp deletions. The authors report an unusual case of familial Turner syndrome in a woman with mosaicism 45,X/46,Xdel(Xp) karyotype with three documented spontaneous pregnancies, which resulted in two daughters with 46,Xdel(X)(p11.4)mat karyotype and a healthy son. The mother was first diagnosed by the age of 11 and did not receive contraceptive medication, due to information that she would be infertile. Both daughters were referred to an endocrinology unit and are now under growth hormone treatment, and have been growing in the 3rd percentile. This family illustrates the complexity and difficulties in counseling, follow-up and treatment in Turner syndrome, namely referring to a tertiary center, fertility and treatment such as growth hormone and hormonal replacement, due to the heterogeneity of the clinical spectrum. PMID- 26824977 TI - A 33-year-old male patient with paternal derived duplication of 14q11.2 14q22.1~22.3: clinical course, phenotypic and genotypic findings. AB - We report on a 33-year-old patient with mosaic interstitial duplication on chromosome 14q11.2-14q22.1~22.3 with severe physical and mental retardation and multiple dysmorphisms. This patient was admitted to our pediatric hospital due to severe dehydration and malnutrition as a result of food refusal. It is an actual phenomenon that patients with severe inborn clinical problems nowadays survive due to progress and care of modern medicine. Nevertheless, transition from pediatric care to adult medicine seems to remain a challenging problem. We demonstrate the clinical course as well as clinical and genetic findings of this adult patient. Comparisons are made to previously reported cases with mosaic trisomy 14 involving a proximal interstitial duplication on the long arm of chromosome 14. PMID- 26824978 TI - Synergistic inhibitory effect of scopoletin and bisdemethoxycurcumin on Tetranychus cinnabarinus (Boisduval) (Acari: Tetranychidae). AB - The study aimed to investigate the synergistic activity of scopoletin and bisdemethoxycurcumin (BDMC) against the carmine spider mite Tetranychus cinnabarinus. The acaricidal activities of mixtures of scopoletin and BDMC against T. cinnabarinus female adults were measured via slide dipping and leaf disc dipping. A mathematical model was established by SPSS software. Bioassays for multiple effects including contact, ovicidal, cowpea root intake, repellency and oviposition inhibitory activity were carried out. The optimal mass ratio of the mixture of scopoletin and BDMC (at their respective LC(50)), the median lethal concentration (LC(50)) and the co-toxicity coefficient were 7:6, 0.19 mg/mL and 129, respectively. LC(50) values of contact activities of the mixture at optimal ratio against adults, nymphs, larvae, and eggs were 0.19, 0.18, 0.06, and 1.52 mg/mL, respectively. LC(50) values of cowpea root intake activity against adults and nymphs were 5.62 and 6.52 mg/mL, respectively. The highest repellent rates against adults and nymphs were 69.5% and 72.5%, respectively. The mixture of scopoletin and BDMC at the optimal mass ratio possessed strong acaricidal activity against T. cinnabarinus at various developmental stages. PMID- 26824979 TI - Performance goals for immunoglobulins and serum free light chain measurements in plasma cell dyscrasias can be based on biological variation. AB - Measurements of immunoglobulins and serum free light chains (sFLC) are frequently used in patients with monoclonal plasma cell dyscrasia (PCD). For optimum patient care, well-defined performance standards or goals for the measured concentrations of immunoglobulins and sFLC are required. Generally, data based on biological variation is a good and reliable method for setting desirable performance standards; this also applies for the measurements of paraprotein and sFLC. The benefits of this approach are several. Among others, it is independent of the clinician, and it provides us with information about reference change value and index of individuality. Several studies on biological variation of both immunoglobulins and sFLC have been published, and mostly the studies are well performed. The studies normally show small within-subject biological variation resulting in strict analytical goals, which in most cases are difficult to meet. Nevertheless, we still need further information on biological variation of immunoglobulins and sFLC in patients with PCD and in the elderly, which are the main target populations for the two measurands. Furthermore, to improve data on biological variation of immunoglobulins and sFLC, studies accounting for number of individuals, samples, and replicates, as well as time length of the studies are needed. PMID- 26824980 TI - Interference of anticoagulants on coagulation testing. PMID- 26824981 TI - Moving towards harmonized reporting of serum and urine protein electrophoresis. AB - During the last decade, surveys by questionnaire in Canada, Australia and New Zealand revealed wide variation in reporting practices by laboratories and individual practitioners in the interpretation of serum and urine protein electrophoresis (PE). Such variation has potential to adversely impact patient outcomes if report structure is inconsistent or if the messaging is incorrectly perceived by the receiving physician. Concerted efforts have been initiated to promote harmonization in the use of interpretative comments. The primary goal is to add value through clear communication with requesting physicians in the interest of quality patient care. Resistance to a harmonized approach largely reflects longstanding personal reporting habits and preferences but change can be more readily embraced if the new system is intuitive, easy to use and saves time in reporting. PMID- 26824982 TI - Prospective validation of an automated chemiluminescence-based assay of renin and aldosterone for the work-up of arterial hypertension. AB - BACKGROUND: The availability of simple and accurate assays of plasma active renin (DRC) and aldosterone concentration (PAC) can improve the detection of secondary forms of arterial hypertension. Thus, we investigated the performance of an automated chemiluminescent assay for DRC and PAC in referred hypertensive patients. METHODS: We prospectively recruited 260 consecutive hypertensive patients referred to an ESH Center for Hypertension. After exclusion of six protocol violations, 254 patients were analyzed: 67.3% had primary hypertension, 17.3% an aldosterone producing adenoma (APA), 11.4% idiopathic hyperaldosteronism (IHA), 2.4% renovascular hypertension (RVH), 0.8% familial hyperaldosteronism type 1 (FH-1), 0.4% apparent mineralocorticoid excess (AME), 0.4% a renin producing tumor, and 3.9% were adrenalectomized APA patients. Bland-Altman plots and Deming regression were used to analyze results. The diagnostic accuracy (area under the curve, AUC of the ROC) of the DRC-based aldosterone-renin ratio (ARRCL) was compared with that of the PRA-based ARR (ARRRIA) using as reference the conclusive diagnosis of APA. RESULTS: At Bland-Altman plot, the DRC and PAC assay showed no bias as compared to the PRA and PAC assay. A tight relation was found between the DRC and the PRA values (concordance correlation coefficient=0.92, p<0.0001) and the PAC values measured with radioimmunoassay and chemiluminescence (concordance correlation coefficient=0.93, p<0.001). For APA identification the AUC of the ARRCL was higher than that of the ARRRIA [0.974 (95% CI 0.940-0.991) vs. 0.894 (95% CI 0.841-0.933), p=0.02]. CONCLUSIONS: This rapid automated chemiluminescent DRC/PAC assay performed better than validated PRA/PAC radioimmunoassays for the identification of APA in referred hypertensive patients. PMID- 26824983 TI - Multiple gene sequencing for risk assessment in patients with early-onset or familial breast cancer. AB - Since BRCA mutations are only responsible for 10-20% of cases of breast cancer in patients with early-onset or a family history and since next-generation sequencing technology allows the simultaneous sequencing of a large number of target genes, testing for multiple cancer-predisposing genes is now being considered, but its significance in clinical practice remains unclear. We then developed a sequencing panel containing 68 genes that had cancer risk association for patients with early-onset or familial breast cancer. A total of 133 patients were enrolled and 30 (22.6%) were found to carry germline deleterious mutations, 9 in BRCA1, 11 in BRCA2, 2 in RAD50, 2 in TP53 and one each in ATM, BRIP1, FANCI, MSH2, MUTYH, and RAD51C. Triple-negative breast cancer (TNBC) was associated with the highest mutation rate (45.5%, p = 0.025). Seven of the 9 BRCA1 mutations and the single FANCI mutation were in the TNBC group; 9 of the 11 BRCA2, 1 of the 2 RAD50 as well as BRIP1, MSH2, MUTYH, and RAD51C mutations were in the hormone receptor (HR)(+)Her2(-) group, and the other RAD50, ATM, and TP53 mutations were in the HR(+)Her2(+) group. Mutation carriers were considered as high-risk to develop malignancy and advised to receive cancer screening. Screening protocols of non-BRCA genes were based on their biologic functions; for example, patients carrying RAD51C mutation received a screening protocol similar to that for BRCA, since BRCA and RAD51C are both involved in homologous recombination. In conclusion, we consider that multiple gene sequencing in cancer risk assessment is clinically valuable. PMID- 26824984 TI - EGFR-activating mutations, DNA copy number abundance of ErbB family, and prognosis in lung adenocarcinoma. AB - In this study, EGFR-activating mutation status and DNA copy number abundances of members of ErbB family were measured in 261 lung adenocarcinomas. The associations between DNA copy number abundances of ErbB family, EGFR-activating mutation status, and prognosis were explored. Results showed that DNA copy number abundances of EGFR, ERBB2, ERBB3, and ERBB4 had associations with overall survival in lung adenocarcinoma with EGFR-activating mutations. In the stratification analysis, only ERBB2 showed significant discrepancy in patients carrying wild type EGFR and other members of ErbB family in patients carrying EGFR-activating mutation. This indicated that CNAs of ErbB family had effect modifications of EGFR-activating mutation status. Findings of this study demonstrate potential molecular guidance of patient management of lung adenocarcinoma with or without EGFR-activating mutations. PMID- 26824985 TI - Delivery of improved oncolytic adenoviruses by mesenchymal stromal cells for elimination of tumorigenic pancreatic cancer cells. AB - Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive malignancies and has poor therapeutic options. We evaluated improved oncolytic adenoviruses (OAds), in which the adenoviral gene E1B19K was deleted or a TRAIL transgene was inserted. Bone marrow mesenchymal stromal cells (MSCs) served as carriers for protected and tumor-specific virus transfers. The infection competence, tumor migration, and oncolysis were measured in cancer stem cell (CSC) models of primary and established tumor cells and in tumor xenografts. All OAds infected and lysed CSCs and prevented colony formation. MSCs migrated into PDA spheroids without impaired homing capacity. Xenotransplantation of non-infected PDA cells mixed with infected tumor cells strongly reduced the tumor volume and the expression of the proliferation marker Ki67 along with a necrotic morphology. Adenoviral capsid protein was detected in tumor xenograft tissue after intravenous injection of infected MSCs, but not in normal tissue, implying tumor specific migration. Likewise, direct in vivo treatment correlated with a strongly reduced tumor volume, lower expression of Ki67 and CD24, and enhanced activity of caspase 3. These data demonstrate that the improved OAds induced efficient oncolysis with the OAd-TRAIL as most promising candidate for future clinical application. PMID- 26824986 TI - Whole exome and targeted deep sequencing identify genome-wide allelic loss and frequent SETDB1 mutations in malignant pleural mesotheliomas. AB - Malignant pleural mesothelioma (MPM), a rare malignancy with a poor prognosis, is mainly caused by exposure to asbestos or other organic fibers, but the underlying genetic mechanism is not fully understood. Genetic alterations and causes for multiple primary cancer development including MPM are unknown. We used whole exome sequencing to identify somatic mutations in a patient with MPM and two additional primary cancers who had no evidence of venous, arterial, lymphovascular, or perineural invasion indicating dissemination of a primary lung cancer to the pleura. We found that the MPM had R282W, a key TP53 mutation, and genome-wide allelic loss or loss of heterozygosity, a distinct genomic alteration not previously described in MPM. We identified frequent inactivating SETDB1 mutations in this patient and in 68 additional MPM patients (mutation frequency: 10%, 7/69) by targeted deep sequencing. Our observations suggest the possibility of a new genetic mechanism in the development of either MPM or multiple primary cancers. The frequent SETDB1 inactivating mutations suggest there could be new diagnostic or therapeutic options for MPM. PMID- 26824987 TI - Dehydropeptidase 1 promotes metastasis through regulation of E-cadherin expression in colon cancer. AB - Dehydropeptidase 1 (DPEP1) is a zinc-dependent metalloproteinase that is expressed aberrantly in several cancers. The role of DPEP1 in cancer remain controversial. In this study, we demonstrate that DPEP1 functions as a positive regulator for colon cancer cell metastasis. The expression of DPEP1 mRNA and proteins were upregulated in colon cancer tissues compared to normal mucosa. Gain of-function and loss-of-function approaches were used to examine the malignant phenotype of DPEP1-expressing or DPEP1-depleted cells. DPEP1 expression caused a significant increase in colon cancer cell adhesion and invasion in vitro, and metastasis in vivo. In contrast, DPEP1 depletion induced opposite effects. Furthermore, cilastatin, a DPEP1 inhibitor, suppressed the invasion and metastasis of DPEP1-expressing cells. DPEP1 inhibited the leukotriene D4 signaling pathway and increased the expression of E-cadherin. We also show that DPEP1 mediates TGF-beta-induced EMT. TGF-beta transcriptionally repressed DPEP1 expression. TGF-beta treatment decreased E-cadherin expression and promoted cell invasion in DPEP1-expressing colon cancer cell lines, whereas it did not affect these parameters in DPEP1-depleted cell lines. These results suggest that DPEP1 promotes cancer metastasis by regulating E-cadherin plasticity and that it might be a potential therapeutic target for preventing the progression of colon cancer. PMID- 26824989 TI - Human melanoma immunotherapy using tumor antigen-specific T cells generated in humanized mice. AB - A major factor hindering the exploration of adoptive immunotherapy in preclinical settings is the limited availability of tumor-reactive human T cells. Here we developed a humanized mouse model that permits large-scale production of human T cells expressing the engineered melanoma antigen MART-1-specific TCR. Humanized mice, made by transplantation of human fetal thymic tissue and CD34+ cells virally-transduced with HLA class I-restricted melanoma antigen (MART-1)-specific TCR gene, showed efficient development of MART-1-TCR+ human T cells with predominantly CD8+ cells. Importantly, MART-1-TCR+CD8+ T cells developing in these mice were capable of mounting antigen-specific responses in vivo, as evidenced by their proliferation, phenotypic conversion and IFN-gamma production following MART-1 peptide immunization. Moreover, these MART-1-TCR+CD8+ T cells mediated efficient killing of melanoma cells in an HLA/antigen-dependent manner. Adoptive transfer of in vitro expanded MART-1-TCR+CD8+ T cells induced potent antitumor responses that were further enhanced by IL-15 treatment in melanoma bearing recipients. Finally, a short incubation of MART-1-specific T cells with rapamycin acted synergistically with IL-15, leading to significantly improved tumor-free survival in recipients with metastatic melanoma. These data demonstrate the practicality of using humanized mice to produce potentially unlimited source of tumor-specific human T cells for experimental and preclinical exploration of cancer immunotherapy. This study also suggests that pretreatment of tumor-reactive T cells with rapamycin in combination with IL-15 administration may be a novel strategy to improve the efficacy of adoptive T cell therapy. PMID- 26824988 TI - Mechanisms of resistance and sensitivity to anti-HER2 therapies in HER2+ breast cancer. AB - Breast Cancer (BC) is a highly prevalent disease. A woman living in the United States has a 12.3% lifetime risk of being diagnosed with breast cancer [1]. It is the most common female cancer and the second most common cause of cancer death in women [2]. Of note, amplification or overexpression of Human Epidermal Receptor 2 (HER2) oncogene is present in approximately 18 to 20% of primary invasive breast cancers, and until personalized therapy became available for this specific BC subtype, the worst rates of Overall Survival (OS) and Recurrence-Free Survival (RFS) were observed in the HER2+ BC cohort, compared to all other types, including triple negative BC (TNBC) [3].HER2 is a member of the epidermal growth factor receptor (EGFR) family. Other family members include EGFR or HER1, HER3 and HER4. HER2 can form heterodimers with any of the other three receptors, and is considered to be the preferred dimerization partner of the other HER or ErbB receptors [4]. Phosphorylation of tyrosine residues within the cytoplasmic domain is the result of receptor dimerization and culminates into initiation of a variety of signalling pathways involved in cellular proliferation, transcription, motility and apoptosis inhibition [5].In addition to being an important prognostic factor in women diagnosed with BC, HER2 overexpression also identifies those patients who benefit from treatment with agents that target HER2, such as trastuzumab, pertuzumab, trastuzumab emtansine (T-DM1) and small molecules tyrosine kinase inhibitors of HER2 [6, 11, 127].In fact, trastuzumab altered the natural history of patients diagnosed with HER2+ BC, both in early and metastatic disease setting, in a major way [8-10]. Nevertheless, there are many women that will eventually develop metastatic disease, despite being treated with anti-HER2 therapy in the early disease setting. Moreover, advanced tumors may reach a point where no anti-HER2 treatment will achieve disease control, including recently approved drugs, such as T-DM1.This review paper will concentrate on major biological pathways that ultimately lead to resistance to anti-HER2 therapies in BC, summarizing their mechanisms. Strategies to overcome this resistance, and the rationale involved in each tactics to revert this scenario will be presented to the reader. PMID- 26824992 TI - The Structure of Cognitive Speed Measures in Old and Young Adults. AB - The speed hypothesis attempts to explain changes in speed of intellectual functioning with increased age by postulating a central speed mechanism or, in a weaker version, multiple speed mechanisms. In this study the issue of structure of measures of speed was addressed by conducting simultaneous confirmatory factor analyses in two age groups at the level of first order and then at the level of second order factors. Sixteen speed measures were included. The analyses were performed in a sample of 149 elderly adults aged 58 to 73 and in a sample of 147 young adults aged 18 to 33. Five first order factors of speed were found, as hypothesized. A model assuming both invariance of factor loadings and of factor intercorrelations was found to fit well the data. Three second order speed factors were necessary to account for the relationships between the first order speed factors, suggesting that a weak version of the speed hypothesis is correct. PMID- 26824990 TI - The effect of perioperative probiotics treatment for colorectal cancer: short term outcomes of a randomized controlled trial. AB - This study was designed to mainly evaluate the anti-infective effects of perioperative probiotic treatment in patients receiving confined colorectal cancer (CRC) respective surgery. From November 2011 to September 2012, a total of 60 patients diagnosed with CRC were randomly assigned to receive probiotic (n = 30) or placebo (n = 30) treatment. The operative and post-operative clinical results including intestinal cleanliness, days to first - flatus, defecation, fluid diet, solid diet, duration of pyrexia, average heart rate, length of intraperitoneal drainage, length of antibiotic therapy, blood index changes, rate of infectious and non-infectious complications, postoperative hospital stay, and mortality were investigated. The patient demographics were not significantly different (p > 0.05) between the probiotic treated and the placebo groups. The days to first flatus (3.63 versus 3.27, p = 0.0274) and the days to first defecation (4.53 versus 3.87, p = 0.0268) were significantly improved in the probiotic treated patients. The incidence of diarrhea was significantly lower (p = 0.0352) in probiotics group (26.67%, 8/30) compared to the placebo group (53.33%, 16/30). There were no statistical differences (p > 0.05) in other infectious and non-infectious complication rates including wound infection, pneumonia, urinary tract infection, anastomotic leakage, and abdominal distension. In conclusion, for those patients undergoing confined CRC resection, perioperative probiotic administration significantly influenced the recovery of bowel function, and such improvement may be of important clinical significance in reducing the short-term infectious complications such as bacteremia. PMID- 26824991 TI - Neuronal hemoglobin in mitochondria is reduced by forming a complex with alpha synuclein in aging monkey brains. AB - Neuronal hemoglobin (nHb) plays a critical role in maintaining normal mitochondrial functioning in the brain. However, in aging and Parkinson's disease (PD) brains, mitochondrial nHb levels are greatly reduced in neurons that accumulate alpha-synuclein (alpha-syn), suggesting a link between the two proteins. In this study, we demonstrate that alpha-syn and Hb can form a complex in both brain tissue and peripheral red blood cells (RBCs) in aging cynomolgus monkeys. nHb-alpha-syn complex levels in the mitochondrial fraction of the striatum decreased with age; this was negatively correlated with levels in the cytoplasmic fraction and in RBCs and was accompanied by a reduction in mitochondrial free nHb. In contrast, no changes in nHb-alpha-syn complex formation or free nHb levels were detected in the cerebellum. In vitro studies using a cultured dopaminergic cell line showed that intracellular accumulation of alpha-syn caused an elevation in nHb-alpha-syn complex levels in both mitochondrial and cytoplasmic fractions as well as a reduction in mitochondrial free nHb. nHb overexpression increased free nHb levels in mitochondria, stabilized mitochondrial membrane potential, and reduced alpha-syn-induced apoptosis. The above results suggest that alpha-syn forms a complex with nHb in selected regions of the aging brain, thereby decreasing mitochondrial function and increasing the risk of PD. PMID- 26824993 TI - Agreement of Personality Profiles Across Observers. AB - To assess cross-observer agreement on personality profiles, an Index of Profile Agreement and an associated coefficient, rpa, are proposed which take into account both the difference between the ratings and the extremeness of their mean. Using data from the Revised NEO Personality Inventory (NEO-PI-R), this coefficient is shown to be superior to Cattell's (1949) rp in identifying matched versus mismatched pairs of peer ratings/self-reports (N = 250) and spouse ratings/self-reports (N = 68). Suggestions are made for the interpretation and use of the two measures of profile agreement for group comparisons and for the interpretation of individual cases. Limitations of the coefficients are also discussed. PMID- 26824994 TI - A Multivariate Descriptive Model of Motivation for Orthodontic Treatment. AB - Motivation for receiving orthodontic treatment is systematically investigated and a multivariate model of this process advanced. An interview schedule is developed out of a mapping sentence and administered to a sample of respondents all of whom had been previously classified as having high need for orthodontic treatment (n = 109). Smallest Space Analyses (SSA) of this data revealed two facets of motivation; treatment reason and information source. The elements of each of these facets (treatment reason =psychological, physical health; source = self, family, dentist) are discussed. Partial Order Scalogram Analysis by base Coordinates (POSAC) is used to demonstrate the roles played by each facet element in structuring motivations. This reflected internal versus external forms of motivation. In this family sources and psychological reasons (internal) form the first dimension of differentiation between respondents, the second (external) being made up of physical reasons. The dentist and self sources were found to play relatively minor roles. PMID- 26824995 TI - A FORTRAN Program for Assessing Unidimensionality of Binary Data Using Holland and Rosenbaum's Methodology. AB - Unidimensionality is one of the important assumptions the data should satisfy in order to apply unidimensional item response models. There are several methodologies available to date to assess the dimensionality of the latent space underlying binary item responses. Rosenbaum (1984) and Holland and Rosenbaum (1986) have proved theorems concerning conditional associations that can be applied to assess dimensionality. Holland and Rosenbaum's method has been applied to assess dimensionality by Zwick (1987), Ben- Simon and Cohen (1990), and Nandakumar (1991) to various test situations. This article outlines the Holland and Rosenbaum's (1986) methodology to assess unidimensionality, illustrates the procedure through a simulated data set, and describes how to interpret the results. PMID- 26824996 TI - Modeling MTMM Data from Additive and Multiplicative Covariance Structures: An Audit of Construct Validity Concordance. AB - The purpose of this study was to determine the extent to which findings derived from four approaches to MTMM analyses were consistent in providing evidence of construct validity related to the measurement of four dimensions of perceived competence (social, academic, English, mathematics) across four maximally dissimilar rating methods (self, teacher, parent, peer). MTMM methodological approaches included that of Campbell-Fiske (1959), the general confirmatory factor analytic (CFA) model (Joreskog, 1969), the CFA (Correlated Uniqueness) model (Marsh, 1988), and the Composite Direct Product model (Browne, 1984). Procedures were applied to data from 158 grade 11 high school adolescents. Advantages, disadvantages, findings, and caveats related to each procedure are discussed. PMID- 26824997 TI - Invariant Standardized Estimated Parameter Change for Model Modification in Covariance Structure Analysis. AB - An estimated parameter change (EPC) has recently been introduced as another criterion to be considered in the process of model modification in covariance structure analysis. Kaplan (1989) provided a standardized version of this statistic (SEPC-K). It has been found that SEPC-K is only partially standardized; specifically, it is not invariant under different scalings of latent and measured variables. In this article, a new SEPC that is invariant to the original metrics of the measured and latent variables is suggested for use in model modification. A multivariate estimated parameter change (MEPC) which estimates changes for a set of fixed parameters to be freed simultaneously is also introduced. A standardized MEPC (SMEPC) is, furthermore, provided. Because there are now three different types of standardized solutions in structural modeling programs, general discussion of standardized solution in covariance structure analysis is provided. The inappropriate use of standardization for scale-specific models is noted. PMID- 26824998 TI - Trait Ratings from Descriptions of Behavior As Mediated by Components of Meaning. AB - This study examined the role language plays in mediating the influence of verbal descriptions of persons on trait ratings of those persons. Subjects were given written descriptions of the behavior of fictitious persons in a work situation and were asked to rate them on fifteen trait- adjective scales. In one condition of the experiment, specific information about certain traits was withheld, forcing subjects to rate persons on traits for which they had no direct behavioral clues. In the other two conditions, the specific information was provided. Providing specific information about a trait directly influenced ratings on that trait even when sufficient general information on that trait was given. In one condition, the influence on the ratings of the additional behavioral clues was such that a new latent variable representing an additional component of meaning was called for in the structural equation model. PMID- 26824999 TI - Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1-high T cells. AB - BACKGROUND: Psoriasis is one of the most common chronic inflammatory diseases of the skin. Recently, IL-17-producing T cells have been shown to play a critical role in psoriatic inflammation. Programmed cell death 1 (PD-1) is a coinhibitory receptor expressed on T cells in various chronic inflammatory diseases; however, the expression and function of PD-1 during psoriatic inflammation have not previously been characterized. OBJECTIVE: We examined PD-1 expression on IL-17A producing T cells from imiquimod-treated mice and patients with psoriasis. Additionally, we investigated the therapeutic effect of recombinant programmed cell death ligand 1 (PD-L1) protein on imiquimod-induced psoriatic inflammation. METHODS: PD-1 expression on IL-17A-producing gammadelta T cells from imiquimod treated mice was examined by means of multicolor flow cytometric analysis. In the psoriatic skin of patients, PD-1 and IL-17A expression was analyzed by using immunofluorescence. The therapeutic effect of PD-L1-Fc fusion protein (PD-L1-Fc) was assessed in imiquimod-treated mice ex vivo and in vivo. RESULTS: During imiquimod-induced psoriatic inflammation, PD-1 is overexpressed on CD27( )Vgamma1(-) gammadelta T cells. Furthermore, PD-1 expression on IL-17A(+) T cells was confirmed in psoriatic skin tissues from patients and imiquimod-treated mice. In the CD27(-)Vgamma1(-) gammadelta T-cell population, Vgamma4(-) gammadelta T cells with Vgamma6 mRNA expression showed a high level of PD-1 expression. Furthermore, these PD-1(hi)Vgamma4(-) (Vgamma6(+)) gammadelta T cells were specialized for anti-CD3-induced IL-17A production, which was inhibited by PD-L1 Fc treatment. In imiquimod-treated mice PD-L1-Fc reduced psoriatic inflammation when given alone and enhanced the therapeutic effect of anti-p40 when given in combination. CONCLUSION: PD-1 is overexpressed in IL-17A-producing T cells in both imiquimod-treated mice and patients with psoriasis. Moreover, recombinant PD L1-Fc alleviates psoriatic inflammation in imiquimod-treated mice. PMID- 26825001 TI - Cancer and aging: Epidemiology and methodological challenges. AB - Epidemiological cancer data shed light on key questions within basic science, clinical medicine and public health. For decades, Denmark has had linkable health registers that contain individual level data on the entire population with virtually complete follow-up. This has enabled high quality studies of cancer epidemiology and minimized the challenges often faced in many countries, such as uncertain identification of the study base, age misreporting, and low validity of the cancer diagnoses. However, methodological challenges still remain to be addressed, especially in cancer epidemiology studies among the elderly and the oldest-old. For example, a characteristic pattern for many cancer types is that the incidence increases up to a maximum at about ages 75-90 years and is then followed by a decline or a leveling off at the oldest ages. It has been suggested that the oldest individuals may be asymptomatic, or even insusceptible to cancer. An alternative interpretation is that this pattern is an artifact due to lower diagnostic intensity among the elderly and oldest-old caused by higher levels of co-morbidities in this age group. Currently, the available cancer epidemiology data are not able to provide clear evidence for any of these hypotheses. PMID- 26825000 TI - No long-term evidence of hyporesponsiveness after use of pneumococcal conjugate vaccine in children previously immunized with pneumococcal polysaccharide vaccine. AB - BACKGROUND: A randomized controlled trial in Fiji examined the immunogenicity and effect on nasopharyngeal carriage after 0, 1, 2, or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) in infancy followed by 23-valent pneumococcal polysaccharide vaccine (23vPPV; Pneumovax) at 12 months of age. At 18 months of age, children given 23vPPV exhibited immune hyporesponsiveness to a micro-23vPPV (20%) challenge dose in terms of serotype-specific IgG and opsonophagocytosis, while 23vPPV had no effect on vaccine-type carriage. OBJECTIVE: This follow-up study examined the long-term effect of the 12-month 23vPPV dose by evaluating the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) administration 4 to 5 years later. METHODS: Blood samples from 194 children (now 5-7 years old) were taken before and 28 days after PCV13 booster immunization. Nasopharyngeal swabs were taken before PCV13 immunization. We measured levels of serotype-specific IgG to all 13 vaccine serotypes, opsonophagocytosis for 8 vaccine serotypes, and memory B-cell responses for 18 serotypes before and after PCV13 immunization. RESULTS: Paired samples were obtained from 185 children. There were no significant differences in the serotype specific IgG, opsonophagocytosis, or memory B-cell response at either time point between children who did or did not receive 23vPPV at 12 months of age. Nasopharyngeal carriage of PCV7 and 23vPPV serotypes was similar among the groups. Priming with 1, 2, or 3 PCV7 doses during infancy did not affect serotype specific immunity or carriage. CONCLUSION: Immune hyporesponsiveness induced by 23vPPV in toddlers does not appear to be sustained among preschool children in this context and does not affect the pneumococcal carriage rate in this age group. PMID- 26825002 TI - Does age affect prognosis in salivary gland carcinoma patients? A national Danish study. AB - AIM: To compare incidence, histology, treatment modalities, disease stages, and outcome in elderly patients (>=70 years) compared to younger (<70 years). METHODS: From the national Danish salivary gland carcinoma database, 871 patients diagnosed with a primary salivary gland carcinoma from January 1990 to December 2005 were identified. Variables necessary for statistical analyses were extracted from the database. RESULTS: The younger patients have a significantly better crude, disease-specific and recurrence-free survival than the elderly ones. In univariate analysis, significantly more patients in the young group were WHO performance status 0 and in disease stage I + II, and they presented with significantly more histological low grade tumors. In multivariate analysis, chronological age seemed to be of no prognostic significance to salivary gland carcinoma patients as opposed to performance status, disease stage and histological grade. CONCLUSIONS: Salivary gland carcinoma patients over the age of 70 years have a poor prognosis compared to younger patients, which can be explained by higher disease stages, more histological high grade subtypes and a poorer performance status at the time of diagnosis. PMID- 26825003 TI - Expression of p53 and HER2/Neu in Kenyan Women With Primary Ovarian Carcinoma. AB - Ovarian carcinomas are a leading cause of cancer mortality among women. Two of the more commonly described markers of prognostic significance in primary ovarian carcinomas are p53 and HER2/neu. Overexpression of both markers is associated with poor prognosis. This study aimed to determine the frequency and pattern of p53 and HER2/neu expression in primary ovarian carcinomas in Kenyan women and to describe the clinical and pathologic features of ovarian carcinomas diagnosed at 3 different hospitals in Kenya. Primary ovarian carcinomas diagnosed at the Departments of Pathology at Aga Khan University Hospital, Nairobi; the Aga Khan Hospital, Kisumu; and the AIC Kijabe Hospital in Kenya over a period of 3 years from January 2009 to December 2011 were recorded. Sixty-seven ovarian carcinomas were identified and blocks retrieved from archives. Hematoxylin-eosin-stained slides of these were reviewed and appropriate sections were stained for p53 and HER2/neu using standard immunohistochemical techniques. The primary outcome was presence and intensity of staining for p53 and HER2/neu. The most frequent malignancy was serous carcinoma. A total of 43.3% (95% confidence interval, 32.1% 55.2%) of carcinomas were positive for p53, and 13.4% (95% confidence interval, 7.2%-23.6%) were positive for HER2/neu. Serous carcinoma and adenocarcinoma, not otherwise specified were more likely to be positive for p53. There was no association noted between the histologic grade or pathologic stage and positivity for either p53 or HER2/neu. The expression of p53 and HER2/neu in primary ovarian carcinomas in Kenyan women is not different from that described in the literature. PMID- 26825004 TI - Endocervicosis of the Uterine Cervix. AB - Endocervicosis is considered a form of Mulleriosis affecting mainly the bladder and is comprised of endocervical-type glands and cysts. It has been rarely described in the uterine cervix where the extensive involvement of cervical and paracervical tissue poses the suspicion of malignancy, mostly minimal-deviation adenocarcinoma. We describe a case of cervical endocervicosis causing long-term symptoms leading to hysterectomy. We provide evidence that this pathology is associated with cesarean section similar with isthmocele. Its differential diagnosis is discussed. PMID- 26825005 TI - Applicability of UV resistant Bacillus pumilus endospores as a human adenovirus surrogate for evaluating the effectiveness of virus inactivation in low-pressure UV treatment systems. AB - Recent studies have demonstrated the potential to use Bacillus pumilus endospores as a surrogate for human adenovirus (HAdV) in UV disinfection studies. The use of endospores has been limited by observations of batch-to-batch variation in UV sensitivity. This study reports on a propagation method that utilizes a commercially available medium to produce UV tolerant B. pumilus endospores with a consistent UV sensitivity. It is further demonstrated that the endospores of B. pumilus strain (ATCC 27142), produced using this protocol (half strength Columbia broth, 5 days incubation, with 0.1mM MnSO4), display a UV dose-response that is similar to that of HAdV. Endospore stocks could be stored in ethanol for up to two months at 4 degrees C without a significant change in UV sensitivity. Synergistic endospore damage was observed by pre-heat treatment of water samples followed by UV irradiation. UV tolerant B. pumilus endospores are a potential surrogate of HAdV for UV treatment performance tests in water utilities which do not have in-house research virology laboratories. PMID- 26825006 TI - Efficacy of Adolescent Suicide Prevention E-Learning Modules for Gatekeepers: A Randomized Controlled Trial. AB - BACKGROUND: Face-to-face gatekeeper training can be an effective strategy in the enhancement of gatekeepers' knowledge and self-efficacy in adolescent suicide prevention. However, barriers related to access (eg, time, resources) may hamper participation in face-to-face training sessions. The transition to a Web-based setting could address obstacles associated with face-to-face gatekeeper training. Although Web-based suicide prevention training targeting adolescents exists, so far no randomized controlled trials (RCTs) have been conducted to investigate their efficacy. OBJECTIVE: This RCT study investigated the efficacy of a Web based adolescent suicide prevention program entitled Mental Health Online, which aimed to improve the knowledge and self-confidence of gatekeepers working with adolescents (12-20 years old). The program consisted of 8 short e-learning modules each capturing an important aspect of the process of early recognition, guidance, and referral of suicidal adolescents, alongside additional information on the topic of (adolescent) suicide prevention. METHODS: A total of 190 gatekeepers (ages 21 to 62 years) participated in this study and were randomized to either the experimental group or waitlist control group. The intervention was not masked. Participants from both groups completed 3 Web-based assessments (pretest, posttest, and 3-month follow-up). The outcome measures of this study were actual knowledge, and participants' ratings of perceived knowledge and perceived self-confidence using questionnaires developed specifically for this study. RESULTS: The actual knowledge, perceived knowledge, and perceived self confidence of gatekeepers in the experimental group improved significantly compared to those in the waitlist control group at posttest, and the effects remained significant at 3-month follow-up. The overall effect sizes were 0.76, 1.20, and 1.02, respectively, across assessments. CONCLUSIONS: The findings of this study indicate that Web-based suicide prevention e-learning modules can be an effective educational method to enhance knowledge and self-confidence of gatekeepers with regard to adolescent suicide prevention. Gatekeepers with limited time and resources can benefit from the accessibility, simplicity, and flexibility of Web-based training. TRIAL REGISTRATION: Netherlands Trial Register NTR3625; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3625 (Archived by WebCite at http://www.webcitation.org/6eHvyRh6M). PMID- 26825007 TI - The use of surgery in the treatment of ER+ early stage breast cancer in England: Variation by time, age and patient characteristics. AB - AIM: To assess whether the proportion of patients aged 70 and over with ER+ operable breast cancer in England who are treated with surgery has changed since 2002, and to determine whether age and individual level factors including tumour characteristics and co-morbidity influence treatment choice. METHODS: A retrospective cohort analysis of routinely collected cancer registration data from two English regions (West Midlands, Northern & Yorkshire) was carried out (n = 17,129). Trends in surgical use over time for different age groups were assessed graphically and with linear regression. Uni- and multivariable logistic regressions were used to assess the effects of age, comorbidity, deprivation and disease characteristics on treatment choice. Missing data was handled using multiple imputation. RESULTS: There is no evidence of a change in the proportion of patients treated surgically over time. The multivariable model shows that age remains an important predictor of whether or not a woman with ER+ operable breast cancer receives surgery after covariate adjustment (Odds ratio of surgery vs no surgery, 0.82 (per year over 70)). Co-morbidity, deprivation, symptomatic presentation, later stage at diagnosis and low grade are also associated with increased probability of non-surgical treatment. CONCLUSION: Contrary to current NICE guidance in England, age appears to be an important factor in the decision to treat operable ER+ breast cancer non-surgically. Further research is needed to assess the role of other age-related factors on treatment choice, and the effect that current practice has on survival and mortality from breast cancer for older women. PMID- 26825009 TI - Voice changes in prodromal Parkinson's disease: Is a new biomarker within earshot? PMID- 26825008 TI - Quantitation of the Minor Tobacco Alkaloids Nornicotine, Anatabine, and Anabasine in Smokers' Urine by High Throughput Liquid Chromatography-Mass Spectrometry. AB - Nicotine is the most abundant alkaloid in tobacco accounting for 95% of the alkaloid content. There are also several minor tobacco alkaloids; among these are nornicotine, anatabine, and anabasine. We developed and applied a 96 well plate based capillary LC-tandem mass spectrometry method for the analysis of nornicotine, anatabine, and anabasine in urine. The method was validated with regard to accuracy and precision. Anabasine was quantifiable to low levels with a limit of quantitation (LOQ) of 0.2 ng/mL even when nicotine, which is isobaric, is present at concentrations >2500-fold higher than anabasine. This attribute of the method is important since anatabine and anabasine in urine have been proposed as biomarkers of tobacco use for individuals using nicotine replacement therapies. In the present study, we analyzed the three minor tobacco alkaloids in urine from 827 smokers with a wide range of tobacco exposures. Nornicotine (LOQ 0.6 ng/mL) was detected in all samples, and anatabine (LOQ, 0.15 ng/mL) and anabasine were detected in 97.7% of the samples. The median urinary concentrations of nornicotine, anatabine, and anabasine were 98.9, 4.02, and 5.53 ng/mL. Total nicotine equivalents (TNE) were well correlated with anatabine (r(2) = 0.714) and anabasine (r(2) = 0.760). TNE was most highly correlated with nornicotine, which is also a metabolite of nicotine. Urine samples from a subset of subjects (n = 110) were analyzed for the presence of glucuronide conjugates by quantifying any increase in anatabine and anabasine concentrations after beta glucuronidase treatment. The median ratio of the glucuronidated to free anatabine was 0.74 (range, 0.1 to 10.9), and the median ratio of glucuronidated to free anabasine was 0.3 (range, 0.1 to 2.9). To our knowledge, this is the largest population of smokers for whom the urinary concentrations of these three tobacco alkaloids has been reported. PMID- 26825010 TI - Microbiological yield from induced sputum compared to oropharyngeal swab in young children with cystic fibrosis. AB - BACKGROUND: Standard respiratory sampling in young children with cystic fibrosis (CF) is by oropharyngeal swab (OPS) as they cannot spontaneously expectorate. Sputum induction (IS) has been poorly investigated in this population. We aimed to compare the bacteriological yield of OPS vs. IS in young children with CF. METHODS: Sequentially paired OPS followed by IS samples was collected in children <5years of age attending a CF clinic in Cape Town, South Africa. RESULTS: IS was successfully paired with OPS in 98/113 (85%) attempts in 32 children (mean+/-SD 19+/-16months), with no serious adverse events. IS culture yield for any CF associated bacteria from IS was 46% vs. 28% from OPS (p=0.01). The sensitivity, specificity, PPV and NPV of OPS compared to IS in isolating CF-associated bacteria were 56%, 96%, 93%, and 72% respectively. CONCLUSION: Sputum induction is feasible, safe and superior to OPS for detecting CF-associated bacteria in young children with CF. PMID- 26825011 TI - The N400 reveals how personal semantics is processed: Insights into the nature and organization of self-knowledge. AB - There is growing recognition that some important forms of long-term memory are difficult to classify into one of the well-studied memory subtypes. One example is personal semantics. Like the episodes that are stored as part of one's autobiography, personal semantics is linked to an individual, yet, like general semantic memory, it is detached from a specific encoding context. Access to general semantics elicits an electrophysiological response known as the N400, which has been characterized across three decades of research; surprisingly, this response has not been fully examined in the context of personal semantics. In this study, we assessed responses to congruent and incongruent statements about people's own, personal preferences. We found that access to personal preferences elicited N400 responses, with congruency effects that were similar in latency and distribution to those for general semantic statements elicited from the same participants. These results suggest that the processing of personal and general semantics share important functional and neurobiological features. PMID- 26825012 TI - Modulation of human auditory spatial scene analysis by transcranial direct current stimulation. AB - Localizing and selectively attending to the source of a sound of interest in a complex auditory environment is an important capacity of the human auditory system. The underlying neural mechanisms have, however, still not been clarified in detail. This issue was addressed by using bilateral bipolar-balanced transcranial direct current stimulation (tDCS) in combination with a task demanding free-field sound localization in the presence of multiple sound sources, thus providing a realistic simulation of the so-called "cocktail-party" situation. With left-anode/right-cathode, but not with right-anode/left-cathode, montage of bilateral electrodes, tDCS over superior temporal gyrus, including planum temporale and auditory cortices, was found to improve the accuracy of target localization in left hemispace. No effects were found for tDCS over inferior parietal lobule or with off-target active stimulation over somatosensory motor cortex that was used to control for non-specific effects. Also, the absolute error in localization remained unaffected by tDCS, thus suggesting that general response precision was not modulated by brain polarization. This finding can be explained in the framework of a model assuming that brain polarization modulated the suppression of irrelevant sound sources, thus resulting in more effective spatial separation of the target from the interfering sound in the complex auditory scene. PMID- 26825013 TI - Predictive Validity of the Premie-Neuro at 3 Months' Adjusted Age and 2 Years' Chronological Age. AB - BACKGROUND: It is difficult to predict which preterm babies are most at risk for poor neurodevelopmental outcomes. A quick, highly predictive assessment tool would aid neonatal clinicians in making decisions about follow-up care. PURPOSE: The purpose of this study was to determine whether performance on the Premie Neuro in the neonatal intensive care unit predicted neurodevelopmental outcomes at 3 months' adjusted age and 24 months' chronological age. METHODS: Thirty-four preterm infants were administered the Premie-Neuro in the neonatal intensive care unit. Infants were assessed using the Infanib and Alberta Infant Motor Scales at 3 months' adjusted age, and using the Bayley Scales of Infant and Toddler Development, Third edition (Bayley-III) at 24 months' chronological age. Scores were analyzed to determine whether Premie-Neuro performance at less than 37 weeks postmenstrual age was predictive of neurodevelopmental outcomes at 3 months' adjusted age and 24 months' chronological age. RESULTS: Premie-Neuro raw scores were predictive of outcomes at 3 months' adjusted age and 24 months' chronological age. Premie-Neuro classifications were not predictive of Infanib and Alberta Infant Motor Scale classifications at 3 months' adjusted age but were predictive of Bayley-III classification at 24 months' chronological age. IMPLICATIONS FOR PRACTICE: Premie-Neuro raw scores may be used by the clinician to identify infants at risk for neurodevelopmental delays. Premie-Neuro classifications should be interpreted cautiously. IMPLICATIONS FOR RESEARCH: More research is needed to determine whether the Premie-Neuro may be used as an adjunct to clinical assessment to identify infants who are most at risk for developmental delay. PMID- 26825014 TI - A Novel Neonatal Feeding Intolerance and Necrotizing Enterocolitis Risk-Scoring Tool Is Easy to Use and Valued by Nursing Staff. AB - BACKGROUND: Preterm infants are at increased risk of developing feeding intolerance and necrotizing enterocolitis. Comprehensive, targeted nursing assessments can evaluate the risk for and identify early signs of these conditions in an effort to prevent their destructive sequela. PURPOSE: While the long-term goal is to develop a validated risk-scoring tool for the prediction of feeding intolerance and necrotizing enterocolitis, the objective of the preliminary phase presented here is to assess the ease of use and nurses' attitudes toward a novel feeding intolerance and necrotizing enterocolitis risk scoring tool. METHODS: A novel risk-scoring nursing tool was implemented in a University of Illinois-affiliated 48-bed level III neonatal intensive care unit. Data were collected from the electronic medical record of all preterm infants with parental consent during the initial 6-month study period. Scoring accuracy (accuracy of selection of risk factors based on electronic medical record data), ease of use, and nurses' attitudes toward the tool were assessed at the study site and by evaluators at a national neonatal nursing conference. RESULTS: Fourteen nurses scored 166 tools on the 63 enrolled infants. Sixteen tools (9.6%) contained errors. Mean study site tool ease of use was 8.1 (SD: 2.2) on a 10 point scale. Ninety percent of conference evaluators agreed/strongly agreed that the tool addressed important knowledge gaps. IMPLICATIONS FOR PRACTICE: The tool is easy to use and valued by nurses. Following validation, widespread implementation is expected to be a clinically feasible means to improve infant clinical outcomes for minimal time and financial cost. IMPLICATIONS FOR RESEARCH: Tool validation and refinement based on nursing feedback will improve its broad applicability and predictive utility. PMID- 26825015 TI - Non-essential role for cilia in coordinating precise alignment of lens fibres. AB - The primary cilium, a microtubule-based organelle found in most cells, is a centre for mechano-sensing fluid movement and cellular signalling, notably through the Hedgehog pathway. We recently found that each lens fibre cell has an apically situated primary cilium that is polarised to the side of the cell facing the anterior pole of the lens. The direction of polarity is similar in neighbouring cells so that in the global view, lens fibres exhibit planar cell polarity (PCP) along the equatorial-anterior polar axis. Ciliogenesis has been associated with the establishment of PCP, although the exact relationship between PCP and the role of cilia is still controversial. To test the hypothesis that the primary cilia have a role in coordinating the precise alignment/orientation of the fibre cells, IFT88, a key component of the intraflagellar transport (IFT) complex, was removed specifically from the lens at different developmental stages using several lens-specific Cre-expressing mouse lines (MLR10- and LR-Cre). Irrespective of which Cre-line was adopted, both demonstrated that in IFT88 depleted cells, the ciliary axoneme was absent or substantially shortened, confirming the disruption of primary cilia formation. However no obvious histological defects were detected even when IFT88 was removed from the lens placode as early as E9.5. Specifically, the lens fibres aligned/oriented towards the poles to form the characteristic Y-shaped sutures as normal. Consistent with this, in primary lens epithelial explants prepared from these conditional knockout mouse lenses, the basal bodies still showed polarised localisation at the apical surface of elongating cells upon FGF-induced fibre differentiation. We further investigated the lens phenotype in knockouts of Bardet-Biedl Syndrome (BBS) proteins 4 and 8, the components of the BBSome complex which modulate ciliary function. In these BBS4 and 8 knockout lenses, again we found the pattern of the anterior sutures formed by the apical tips of elongating/migrating fibres were comparable to the control lenses. Taken together, these results indicate that primary cilia do not play an essential role in the precise cellular alignment/orientation of fibre cells. Thus, it appears that in the lens cilia are not required to establish PCP. PMID- 26825016 TI - A food-grade fimbrial adhesin FaeG expression system in Lactococcus lactis and Lactobacillus casei. AB - Enterotoxigenic Escherichia coli (ETEC) infection is the major cause of diarrhea in neonatal piglets. The fimbriae as colonizing factor in the pathogenesis of ETEC constitute a primary target for vaccination against ETEC. Lactic acid bacteria (LAB) are attractive tools to deliver antigens at the mucosal level. With the safety of genetically modified LAB in mind, a food-grade secretion vector (pALRc or pALRb) was constructed with DNA entirely from LAB, including the replicon, promoter, signal peptide, and selection marker alanine racemase gene (alr). To evaluate the feasibility of the system, the nuclease gene (nuc) from Staphylococcus aureus was used as a reporter to be expressed in both Lactococcus lactis and Lactobacillus casei. Subsequently, the extracellular secretion of the fimbrial adhesin FaeG of ETEC was confirmed by Western blot analysis. These results showed that this food-grade expression system has potential as the delivery vehicle for the safe use of genetically modified LAB for the development of vaccines against ETEC infection. PMID- 26825018 TI - Reply to: the use of advanced airway management devices in clinical practice. PMID- 26825017 TI - Preoperative hydration with 0.9% normal saline to prevent acute kidney injury after major elective open abdominal surgery: A randomised controlled trial. AB - BACKGROUND: Postoperative acute kidney injury (AKI) is the second leading cause of hospital-acquired AKI. Although many preventive strategies have been tested, none of them has been totally effective. OBJECTIVE: We investigated whether preoperative intravenous hydration with 0.9% normal saline could prevent postoperative AKI. DESIGN: Randomised controlled trial. SETTING: University Ramon y Cajal Hospital, Spain, from June 2006 to February 2011. PATIENTS: Total 328 inpatients scheduled for major elective open abdominal surgery. INTERVENTION: 0.9% normal saline at a dose of 1.5 ml kg h for 12 h before surgery. MAIN OUTCOME MEASURES: The primary outcome was the overall postoperative AKI incidence during the first week after surgery defined by risk, injury, failure, loss, end-stage kidney disease (RIFLE) and AKI network (AKIN) creatinine criteria. Secondary endpoints were the need for ICU admission, renal replacement therapy during the study period and adverse events and hospital mortality during hospital admission. RESULTS: There was no difference in the incidence of AKI between groups: 4.7% in the normal saline group versus 5.0% in the control group and 11.4% in the 0.9% normal saline group versus 7.9% in the control group as assessed by the RIFLE and AKIN creatinine criteria, respectively. Absolute risk reductions (95% confidence interval) were -0.3% (-5.3 to 4.7%) for RIFLE and 3.5% (-10.2 to 3.6%) for AKIN. ICU admission after surgery was required in 44.5% of all participants. Only 2 (0.7%) patients required renal replacement therapy during the first week after surgery. The analysis of adverse events did not show statistically significant differences between the groups except for pain. In our population, 8 (2.4%) patients died during their hospital admission. CONCLUSION: Intravenous hydration with 0.9% normal saline before major open abdominal surgery was not effective in preventing postoperative AKI. No safety concerns were identified during the trial. TRIAL REGISTRATIONS: Clinical trials.gov: NCT00953940 and EUDRA CT: 2005 004755-35. PMID- 26825019 TI - Clinical pertinence and diagnostic accuracy of an evidence-based monitoring system: Custos. PMID- 26825021 TI - A randomized controlled trial on the benefits and respiratory adverse effects of morphine for refractory dyspnea in patients with COPD: Protocol of the MORDYC study. AB - Dyspnea is one of the most reported symptoms of patients with advanced Chronic Obstructive Pulmonary Disease (COPD) and is often undertreated. Morphine has proven to be an effective treatment for dyspnea and is recommended in clinical practice guidelines, but questions concerning benefits and respiratory adverse effects remain. This study primarily evaluates the impact of oral sustained release morphine (morphine SR) on health-related quality of life and respiratory adverse effects in patients with COPD. Secondary objectives include the impact on exercise capacity, the relationship between description and severity of dyspnea and the presence of a clinically relevant response to morphine, and cost effectiveness. A single-center, randomized, double blind, placebo controlled intervention study will be performed in 124 patients with COPD who recently completed a comprehensive pulmonary rehabilitation program. Participants will receive 20-30 mg/24h morphine SR or placebo for four weeks. After the intervention, participants will be followed for twelve weeks. Outcomes include: the COPD Assessment Test, six minute walking test, Multidimensional Dyspnea Scale and a cost diary. Furthermore, lung function and arterial blood gasses will be measured. These measures will be assessed during a baseline and outcome assessment, two home visits, two phone calls, and three follow-up assessments. The intervention and control group will be compared using uni- and multivariate regression analysis and logistic regression analysis. Finally, an economic evaluation will be performed from a societal and healthcare perspective. The current manuscript describes the rationale and methods of this study and provides an outline of the possible strengths, weaknesses and clinical consequences. PMID- 26825020 TI - The BestFIT trial: A SMART approach to developing individualized weight loss treatments. AB - Behavioral weight loss programs help people achieve clinically meaningful weight losses (8-10% of starting body weight). Despite data showing that only half of participants achieve this goal, a "one size fits all" approach is normative. This weight loss intervention science gap calls for adaptive interventions that provide the "right treatment at the right time for the right person." Sequential Multiple Assignment Randomized Trials (SMART), use experimental design principles to answer questions for building adaptive interventions including whether, how, or when to alter treatment intensity, type, or delivery. This paper describes the rationale and design of the BestFIT study, a SMART designed to evaluate the optimal timing for intervening with sub-optimal responders to weight loss treatment and relative efficacy of two treatments that address self-regulation challenges which impede weight loss: 1) augmenting treatment with portion controlled meals (PCM) which decrease the need for self-regulation; and 2) switching to acceptance-based behavior treatment (ABT) which boosts capacity for self-regulation. The primary aim is to evaluate the benefit of changing treatment with PCM versus ABT. The secondary aim is to evaluate the best time to intervene with sub-optimal responders. BestFIT results will lead to the empirically supported construction of an adaptive intervention that will optimize weight loss outcomes and associated health benefits. PMID- 26825022 TI - Design, development and deployment of a Diabetes Research Registry to facilitate recruitment in clinical research. AB - BACKGROUND AND AIM: A major challenge in conducting clinical trials/studies is the timely recruitment of eligible subjects. Our aim is to develop a Diabetes Research Registry (DRR) to facilitate recruitment by matching potential subjects interested in research with approved clinical studies using study entry criteria abstracted from their electronic health records (EHR). METHOD: A committee with expertise in diabetes, quality improvement, information technology, and informatics designed and developed the DRR. Using a hybrid approach, we identified and consented patients interested in research, abstracted their EHRs to assess common eligibility criteria, and contacted them about their interest in participating in specific studies. Investigators submit their requests with study entry criteria to the DRR which then provides a list of potential subjects who may be directly contacted for their study. The DRR meets all local, regional and federal regulatory requirements. RESULTS: After 5 years, the DRR has over 5000 registrants. About 30% have type 1 diabetes and 70% have type 2 diabetes. There are almost equal proportions of men and women. During this period, 31 unique clinical studies from 19 unique investigators requested lists of potential subjects for their studies. Eleven grant applications from 10 unique investigators used aggregated counts of potentially eligible subjects in their applications. CONCLUSION: The DRR matches potential subjects interested in research with approved clinical studies using study entry criteria abstracted from their EHR. By providing large lists of potentially eligible study subjects quickly, the DRR facilitated recruitment in 31 clinical studies. PMID- 26825023 TI - Innovations for phase I dose-finding designs in pediatric oncology clinical trials. AB - Phase I oncology clinical trials are designed to identify the optimal dose that will be recommended for phase II trials. In pediatric oncology, the conduct of those trials raises specific challenges, as the disease is rare with limited therapeutic options. In addition, the tolerance profile is known from adult trials. This paper provides a review of the major recent developments in the design of these trials, inspired by the need to cope with the specific challenges of dose finding in cancer pediatric oncology. We reviewed simulation studies comparing designs dedicated to address these challenges. We also reviewed the design used in published dose-finding trials in pediatric oncology over the period 2009-2014. Three main fields of innovation were identified. First, designs that were developed in order to relax the rules for more flexible inclusions. Second, methods to incorporate data emerging from adult studies. Third, designs accounting for toxicity evaluation at repeated cycles in pediatric oncology. In addition to this overview, we propose some further directions for designing pediatric dose-finding trials. PMID- 26825024 TI - VEGF Gene Polymorphisms Affect Serum Protein Levels and Alter Disease Activity and Synovial Lesions in Rheumatoid Arthritis. AB - BACKGROUND: Our study investigated 2 common single-nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) for their influences on serum VEGF levels, disease activity, and synovial lesions in rheumatoid arthritis (RA). MATERIAL/METHODS: Clinical information and venous blood samples were collected from 98 RA patients and 100 healthy controls. Genotyping on samples from the subjects was performed using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Serum VEGF levels were determined using the enzyme-linked immunosorbent assay (ELISA). The synovial thickness and joint effusion of 28 joints were measured in RA patients, and total sharp score (TSS) and disease activity score (DAS) of 28 joints were recorded. RESULTS: The genotype and allele frequencies of VEGF rs833070 (G>A) and rs3025030 (G>C) were significantly different between RA group and control group (all P<0.05). VEGF rs833070 and rs3025030 polymorphisms were associated with increasing VEGF serum levels in the RA group (all P<0.01). Statistically significant difference was observed in DAS28 between the different genotypes of VEGF rs833070 in RA patients (P<0.05). Importantly, significant differences in synovial thickening, joint effusion and synovial angiogenesis were observed between the different genotypes of VEGF rs833070 and rs3025030 polymorphisms (all P<0.05). CONCLUSIONS: Our study provides evidence that VEGF polymorphisms might be important indicators of disease activity and synovial lesions, and prognostic factors in evaluating the treatment effectiveness in RA. PMID- 26825025 TI - Association of 25-hydroxyvitamin D status with obesity as well as blood glucose and lipid concentrations in children and adolescents in China. AB - BACKGROUND: Vitamin D is an essential micronutrient during the growth and development of the human body. Previously, most of the researches about the relationship of vitamin D and obesity were focused on adults. In this paper, the relationship between serum 25-hydroxyvitamin D [25(OH)D] and obesity among children and adolescents in China was analyzed. METHODS: From August 2012 to August 2014, 443 children and adolescents participated in this study. Serum 25(OH)D, lipid and glucose were measured in the laboratory. All the participants were classified into 2 groups (obese and non-obese group) on the basis of their BMI. They were then categorized into vitamin D deficiency, vitamin D insufficiency and vitamin D normal groups according to the serum concentrations of 25(OH)D. RESULTS: The concentration of serum 25(OH)D in the obese group was significantly lower than that of the non-obese group (P<0.001). The concentration of total cholesterol, low-density lipoprotein cholesterol, fasting blood glucose, fasting insulin and homeostasis model assessment for insulin resistance showed significant differences between the obese and non-obese groups (P<0.05). CONCLUSIONS: Children and adolescents suffering from obesity are more likely to have lower concentrations of serum 25(OH)D. PMID- 26825026 TI - A new self-partition clustering method for robust identification of subsets with heterogeneous size and density and its clinical application to leukocyte differential counting. AB - BACKGROUND: Identification of clusters in 2-dimensional scatterplots generated by hematology analyzer is a classical challenge. Conventional clustering algorithms fail to process cases with complicated mixtures of overlapping clusters and noise. METHOD: A new method was developed that features an image processing algorithm for rational identification of initial clusters and a self-partition clustering (SPC) algorithm with iterative truncation-correction (ITC) method to handle overlapping and noise. All clusters are assumed to follow bivariate Gaussian distributions with specified means, SDs, and correlation coefficient. While, each data point is assumed to belong to all clusters but with different proportions according to the likelihood of belonging to each cluster (computed by the Mahalanobis distance) and the data size of the cluster. Bivariate cluster statistics are computed in consideration of a weight factor determined cluster by cluster by each data point. In the computation, the ITC method minimizes the effect of overlapping and data. RESULTS: Performance of SPC/ITC method was evaluated by its application to differential leukocyte counting. It showed comparable performance with manual counting and much better performance than the commonly used expectation maximum algorithm. CONCLUSION: The SPC/ITC method showed superior performance in situations with overlapping and low-density clusters such as leukopenia or leukocytosis. PMID- 26825027 TI - Nurse education and willingness to provide spiritual care. AB - BACKGROUND: Spiritual care is a critical part of holistic care, and nurses require adequate preparation to address the spiritual needs of patients. However, nurses' willingness to provide such care has rarely been reported. Hence, nurses' education, and knowledge of spiritual care, as well as their willingness to provide it require further study. METHODS: A convenience sample of 200 nurses participated in the study. Quantitative data were collected using a 21-item Spiritual Care Needs Inventory (content validity index=.87; Cronbach's alpha=.96). RESULTS: The majority of participants were female (96.5%, n=193) between 21 and 59years old (mean=35.1years). Moreover, the majority of participants had a Bachelor's degree (74.0%, n=148) and 1-36years of clinical experience (mean=12.13years). Regarding religious beliefs, 63 (31.5%) had no religious belief, and 93 (46.5%) did not engage in any religious activity. Overall, the nurses were willing to provide spiritual care, although only 25 (12.5%) felt that they had received adequate education. CONCLUSION: The findings of this study indicate the need for further educational preparation in spiritual care for nurses. Specifically, additional teaching materials are required that are more directly related to spiritual care. Greater emphasis should be placed on different subject areas in school-based education, continuing education, and self learning education according to the needs of nurses. Since spiritual care education needs policy support, in-depth discussions should take place regarding the approach and cultural environment for providing spiritual care in future nursing courses. Moreover, further studies should investigate barriers in providing spiritual nursing care to patients and whether they are the results of a lack of relevant knowledge or other factors. PMID- 26825028 TI - Routine pre-operative group cross-matching in total knee arthroplasty: A review of this practice in an Asian population. AB - BACKGROUND: Routine pre-operative group cross-match (GXM) and post-operative haemoglobin level measurements are performed for all total knee arthroplasty (TKA) patients in many institutions. We aimed to determine whether this practice is justified, and to identify predictors for post-operative transfusion. MATERIALS AND METHODS: A retrospective review was performed on 226 TKA procedures performed between Jan. 2011 and Dec. 2013. Patients' demographics and clinical details including co-morbidities, pre-operative laboratory results, type of anaesthesia, surgery duration, post-operative haemoglobin level and transfusion requirement were reviewed. RESULTS: Overall transfusion rate was 10.6% (n=24). Cross-match to transfusion ratio was 6.5. The cross-match to transfusion ratio (C:T ratio) was measured as the ratio of number of units of blood cross-matched to units of blood transfused. In females, relative risk of transfusion between patients with pre-operative haemoglobin below 12.0 and those above or equal to 12.0 was significant at 4.53 (Confidence interval (CI) 2.16 to 9.53). The relative risk of transfusion between patients above 65 years of age compared to those below 65 years of age was 1.13 (CI 1.03 to 1.23). Multivariate analysis revealed advancing age (p=0.044) and lower preoperative haemoglobin (p<0.001) as significant variables associated with post-operative transfusion. CONCLUSION: Post-operative transfusion rates are low and excessive pre-operative GXM and post operative haemoglobin checks are contributing to unnecessary medical costs. Predictors of blood transfusion risk in unilateral TKA in our cohort of Asian population were advancing age and lower pre-operative haemoglobin level. Type and screen tests should be performed for all other patients. LEVEL OF SCIENTIFIC EVIDENCE: 3. PMID- 26825029 TI - Surgical induced models of joint degeneration in the ovine stifle: Magnetic resonance imaging and histological assessment. AB - BACKGROUND: The purposes of this study were to (1) validate and assess the reliability of a modified magnetic resonance semi-quantitative score (sheep Magnetic Resonance osteoarthritis Knee Score (sMOAKS)) to evaluate joint degeneration in the ovine knee and to (2) investigate whether the transection of the anterior cruciate ligament (ACL), isolated or in combination with meniscal injuries, reproduce the degenerative changes described in the meniscectomized sheep. METHODS: Twenty sheep were randomly subjected to one of the following injuries to induce osteoarthritis (OA): ACL transection (ACLt), mid-body transection of the medial meniscus, ACLt combined with complete medial meniscectomy and complete medial meniscectomy. OA assessment was performed eight weeks postoperatively with sMOAKS, Mankin and Osteoarthritis Research Society International (OARSI) histological scores. RESULTS: sMOAKS showed very good to excellent reliability (kappa=0.61 to 1.0) for the majority of features evaluated. sMOAKS revealed small differences between groups (p<0.05) being the ACLt group the most affected. We observed a strong positive correlation between the three scales in the evaluation of femoro-tibial articular cartilage (AC) (r=0.829, r=0.917, r=0.879). CONCLUSIONS: sMOAKS is a reliable semi-quantitative Magnetic Resonance (MR) scale to evaluate and quantify the effect of different OA induction lesions in the ovine knee and presents a high correlation with Mankin and OARSI scales in the evaluation of femoro-tibial AC. Although minor differences were observed between the different surgical procedures for the induction of OA, ACLt proved to be the intervention that produced the highest amount of degeneration eight weeks postoperatively. LEVEL OF EVIDENCE: II. PMID- 26825031 TI - Healthcare Managers' Experiences of Leading the Implementation of Video Conferencing in Discharge Planning Sessions: An Interview Study. AB - This article describes healthcare managers' experiences of leading the implementation of video conferencing in discharge planning sessions as a new tool in everyday practice. Data collection took place through individual interviews and the interviews were analyzed using qualitative content analysis with an inductive approach. The results indicate that managers identified two distinct leadership perspectives when they reflected on the implementation process. They described a desired way of leading the implementation and communicating about the upcoming change, understanding and securing support for decisions, as well as ensuring that sufficient time is available throughout the change process. They also, however, described how they perceived that the implementation process was actually taking place, highlighting the lack of planning and preparation as well as the need for support and to be supportive, and having the courage to adopt and lead the implementation. It is suggested that managers at all levels require more information and training in how to encourage staff to become involved in designing their everyday work and in the implementation process. Managers, too, need ongoing organizational support for good leadership throughout the implementation of video conferencing in discharge planning sessions, including planning, start-up, implementation, and evaluation. PMID- 26825032 TI - Maraviroc-intensified combined antiretroviral therapy improves cognition in virally suppressed HIV-associated neurocognitive disorder. AB - OBJECTIVE: To investigate whether intensification of combined antiretroviral therapy (cART) with the CC chemokine receptor type 5 (CCR5) entry inhibitor maraviroc leads to improvement in global neurocognitive functioning in virally suppressed men with HIV-associated neurocognitive disorder (HAND). DESIGN: Prospective, double observer-blinded, open-label pilot randomized-controlled trial. Participants were randomized to remain on their existing cART regimen (control arm; n = 8) or receive maraviroc-intensification (maraviroc arm; n = 9). METHODS: Participants completed a five-domain neuropsychological battery at baseline, 6- and 12-month visits. Raw scores were transformed into age-corrected z-scores and averaged into a global z-score. Single voxel (H)-magnetic resonance spectroscopy (MRS) major cerebral metabolite concentrations were collected at baseline and 12 months in the basal ganglia and frontal white matter and quantified using jMRUI. Neuroinflammatory biomarkers cerebrospinal fluid neopterin and beta2-microglobulin were also measured. RESULTS: Fourteen of the 17 participants completed the study: nine maraviroc arm and five control. We found medium to large effect sizes in favour of improved global neurocognitive performance in the maraviroc arm over time {arm*time interaction: P < 0.05; 6 month: [beta=-0.10, standard error (SE)= 0.04, 90% confidence interval (90%CI)= 0.18,.03; P < 0.03] yielding a large effect-size d = 0.77 (90%CI = -0.19,1.71); 12 month: [beta=-0.01; SE = 0.05; 90%CI = -0.09, 0.06; P < 0.77] yielding a moderate effect-size d = 0.55 (90%CI = -0.47,1.55)}. No treatment-related changes were detected for H-MRS metabolites or cerebrospinal fluid biomarkers. CONCLUSION: This pilot study provides feasibility, tolerability, proof-of-concept and preliminary evidence for clinically relevant neurocognitive improvement in cART enhancement with maraviroc in virally suppressed HAND patients. Lack of concomitant brain metabolite and biomarker change may be related to complex dynamics of brain repair. PMID- 26825033 TI - Preventing long-term tenofovir renal toxicity by pharmacokinetic assessment. PMID- 26825034 TI - Severe strongyloidiasis in AIDS: relative risk obscured by absolute rarity. PMID- 26825035 TI - Atazanavir use and carotid intima media thickness progression in HIV: potential influence of bilirubin. PMID- 26825036 TI - Atypical ocular manifestation of primary varicella zoster virus infection as the first manifestation of AIDS. PMID- 26825037 TI - Endothelin-1 in the tumor microenvironment correlates with melanoma invasion. AB - Endothelin-1 (ET-1) is a vasoactive peptide that also plays a role in the tanning response of the skin. Animal and cell culture studies have also implicated ET-1 in melanoma progression, but no association studies have been performed to link ET-1 expression and melanoma in humans. Here, we present the first in-vivo study of ET-1 expression in pigmented lesions in humans: an ET-1 immunohistochemical screen of melanocytic nevi, melanoma in situ lesions, invasive melanomas, metastatic melanomas, and blue nevi was performed. Twenty-six percent of melanocytic nevi and 44% of melanoma in situ lesions demonstrate ET-1 expression in the perilesional microenvironment, whereas expression in nevus or melanoma cells was rare to absent. In striking contrast, 100% of moderately to highly pigmented invasive melanomas contained numerous ET-1-positive cells in the tumor microenvironment, with 79% containing ET-1-positive melanoma cells, confirmed by co-staining with melanoma tumor marker HMB45. Hypopigmented invasive melanomas had reduced ET-1 expression, suggesting a correlation between ET-1 expression and pigmented melanomas. ET-1-positive perilesional cells were CD68-positive, indicating macrophage origin. Sixty-two percent of highly pigmented metastatic melanomas demonstrated ET-1 expression in melanoma cells, in contrast to 28.2% of hypopigmented specimens. Eighty-nine percent of benign nevi, known as blue nevi, which have a dermal localization, were associated with numerous ET-1-positive macrophages in the perilesional microenvironment, but no ET-1 expression was detected in the melanocytes. We conclude that ET-1 expression in the microenvironment increases with advancing stages of melanocyte transformation, implicating a critical role for ET-1 in melanoma progression, and the importance of the tumor microenvironment in the melanoma phenotype. PMID- 26825038 TI - Radicality of initial surgery for primary malignant melanoma of the vagina. AB - Radical surgery is considered not to improve the prognosis of primary malignant melanoma of the vagina (PMMV). This study was carried out to review the general consensus. A systematic review was performed on the basis of data from 10 patients in our cohort and 147 patients in the previous literature. The radicality of the initial surgery (RAINS) score was defined as the total number of points in terms of the resected organs. The target organs were the vagina, vulva, urethra, bladder, uterus, anus, rectum, pelvic lymph nodes, and inguinal lymph nodes. Overall survival (OS) according to the RAINS score was analyzed using the Kaplan-Meier method. Information on tumor stage, size, and depth of invasion was not obtained in 15, 47, and 43% of patients, respectively. The median follow-up period was 18 months. OS with a RAINS score of at least 7 was significantly longer than that with a RAINS score of up to 6 (median survival time, 41 vs. 19 months; log-rank test, P=0.037), despite the fact that the former group included significantly more patients with advanced-stage disease. A significant difference in OS was not found between patients with a RAINS score of at least 6 and up to 5. The therapeutic significance of radical surgery for PMMV has not been assessed appropriately in previous studies because of the lack of comparability among groups and differences in the definitions of surgical radicality. Patients with PMMV might benefit from initial surgery with appropriate surgical radicality, despite incomplete validation of the RAINS score. PMID- 26825039 TI - Pepper protein phosphatase type 2C, CaADIP1 and its interacting partner CaRLP1 antagonistically regulate ABA signalling and drought response. AB - Abscisic acid (ABA) is a key phytohormone that regulates plant growth and developmental processes, including seed germination and stomatal closing. Here, we report the identification and functional characterization of a novel type 2C protein phosphatase, CaADIP1 (Capsicum annuum ABA and Drought-Induced Protein phosphatase 1). The expression of CaADIP1 was induced in pepper leaves by ABA, drought and NaCl treatments. Arabidopsis plants overexpressing CaADIP1 (CaADIP1 OX) exhibited an ABA-hyposensitive and drought-susceptible phenotype. We used a yeast two-hybrid screening assay to identify CaRLP1 (Capsicum annuum RCAR-Like Protein 1), which interacts with CaADIP1 in the cytoplasm and nucleus. In contrast to CaADIP1-OX plants, CaRLP1-OX plants displayed an ABA-hypersensitive and drought-tolerant phenotype, which was characterized by low levels of transpirational water loss and increased expression of stress-responsive genes relative to those of wild-type plants. In CaADIP1-OX/CaRLP1-OX double transgenic plants, ectopic expression of the CaRLP1 gene led to strong suppression of CaADIP1-induced ABA hyposensitivity during the germinative and post-germinative stages, indicating that CaADIP1 and CaRLP1 act in the same signalling pathway and CaADIP1 functions downstream of CaRLP1. Our results indicate that CaADIP1 and its interacting partner CaRLP1 antagonistically regulate the ABA-dependent defense signalling response to drought stress. PMID- 26825040 TI - Papillary Muscle Rupture Following Non-ST-Elevation Myocardial Infarction: A Case Report. AB - Papillary muscle rupture is a serious mechanical complication of acute myocardial infarction typically seen within 5-7 days following transmural ST-elevation myocardial infarction. The incidence of papillary muscle rupture has markedly decreased in the modern era due to improved diagnosis and early coronary revascularization of ST-elevation myocardial infarction. As a result, papillary muscle rupture is increasingly seen following non-ST-elevation myocardial infarction where both diagnosis and revascularization can be delayed. In this report, we describe two cases of papillary muscle rupture following delayed presentation of non-ST-elevation myocardial infarction and delayed recognition of papillary muscle rupture. PMID- 26825041 TI - An innovative regenerative treatment of scars with dermal micrografts. AB - BACKGROUND: Pathological scars occur following injuries and are often considered esthetically unattractive. Several strategies have been attempted to improve these types of scars using both surgical and nonsurgical methods. The most common treatments include cryotherapy, intralesional corticosteroid injections, 5 fluorouracil, bleomycin, interferon, and verapamil. AIMS: In this study, we aim to investigate the effectiveness of dermal autologous micrografts in the treatment of pathological scars resulting from burns, trauma, or any iatrogenic source. METHODS: We used a new clinical practice called Rigenera Protocol to obtain autologous micrografts which were in turn injectable in the patients. RESULTS: A significant improvement was observed in appearance and texture of the exaggerated scars in all cases following already 4 months of autologous micrograft treatment We have also shown that these micrografts are composed of mesenchymal stem cells and in addition, histological evaluation verified restoration of the structural layers immediately below the epidermis and a horizontal realignment of collagen fibers in the papillary dermis. CONCLUSION: Our results clearly demonstrate the optimal outcomes obtained following treatment with dermal micrografts on exaggerated scars with different etiologies. However, further studies are required to confirm the efficacy of this new technique. PMID- 26825042 TI - Young Children and Screen Time: It is Time to Consider Healthy Bodies as Well as Healthy Minds. PMID- 26825043 TI - Video-based Assessment of Peripheral Intravenous Catheter Insertion in the Resuscitation Area of a Pediatric Emergency Department. AB - OBJECTIVE: The objective was to describe the frequency of and factors associated with prolonged peripheral intravenous catheter (PIV) insertion in the resuscitation area of a pediatric emergency department (PED). METHODS: Video based study of a consecutive sample of nontrauma patients undergoing PIV insertion in the resuscitation area of a PED. Preexisting videos were the main data source. The primary outcome was patients with prolonged duration of PIV insertion (>90 seconds from start of first attempt to successful flush/blood draw). Logistic regression identified variables independently associated with prolonged PIV insertion. RESULTS: A total of 151 consecutive nontrauma patients underwent PIV insertion during a 2.5-month period. Sixty-nine patients (46%) had prolonged PIV insertion, including 14 for whom PED providers failed to insert PIVs. For patients with successful PIV insertion by PED providers, median duration was 48 seconds (interquartile range [IQR] = 23 to 295 seconds). Vascular access was ultimately achieved for 13 patients (93%) with initial insertion failure by the PED team (10 non-PED personnel, three intraosseous lines), with a median duration of 26.7 minutes (IQR = 19.9 to 34.2 minutes). Age <= 2 years (ORadj = 6.9; 95% confidence interval [CI] = 2.9 to 16.1) and musculoskeletal contractures (ORadj = 5.3; 95% CI = 1.6 to 17.2) were independently associated with prolonged PIV insertion. CONCLUSIONS: Prolonged PIV insertion is common in a PED resuscitation area. When PED providers could not insert a PIV, time to insertion was very long. Young patients and those with contractures were at particular risk for prolonged and failed PIV placement. When emergent vascular access is required, alternative approaches should be considered early for these patients. PMID- 26825044 TI - Exploring the Role of Polycythemia in Patients With Cyanosis After Palliative Congenital Heart Surgery. AB - OBJECTIVES: To understand the relationship between polycythemia and clinical outcome in patients with hypoplastic left heart syndrome following the Norwood operation. DESIGN: A retrospective, single-center cohort study. SETTING: Pediatric cardiovascular ICU, university-affiliated children's hospital. PATIENTS: Infants with hypoplastic left heart syndrome admitted to our medical center from September 2009 to December 2012 undergoing stage 1/Norwood operation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline demographic and clinical information including first recorded postoperative hematocrit and subsequent mean, median, and nadir hematocrits during the first 72 hours postoperatively were recorded. The primary outcomes were in-hospital mortality and length of hospitalization. Thirty-two patients were included in the analysis. Patients did not differ by operative factors (cardiopulmonary bypass time and cross-clamp time) or traditional markers of severity of illness (vasoactive inotrope score, lactate, saturation, and PaO2/FIO2 ratio). Early polycythemia (hematocrit value > 49%) was associated with longer cardiovascular ICU stay (51.0 [+/- 38.6] vs 21.4 [+/- 16.2] d; p < 0.01) and total hospital length of stay (65.0 [+/- 46.5] vs 36.1 [+/- 20.0] d; p = 0.03). In a multivariable analysis, polycythemia remained independently associated with the length of hospitalization after controlling for the amount of RBC transfusion (weight, 4.36 [95% CI, 1.35 7.37]; p < 0.01). No difference in in-hospital mortality rates was detected between the two groups (17.6% vs 20%). CONCLUSIONS: Early polycythemia following the Norwood operation is associated with longer length of hospitalization even after controlling for blood cell transfusion practices. We hypothesize that polycythemia may be caused by hemoconcentration and used as an early marker of capillary leak syndrome. PMID- 26825045 TI - Strategies to Maximize Enrollment in a Prospective Study of Comatose Children in the PICU. AB - OBJECTIVES: To analyze barriers to recruitment encountered during a prospective study in the PICU and evaluate strategies implemented to improve recruitment. DESIGN: Prospective observational study of continuous electroencephalogram monitoring in comatose children. SETTING: PICUs at four North American institutions. PATIENTS: Patients with a Glasgow Coma Scale score of less than or equal to 8 for at least an hour. INTERVENTIONS: Four strategies to increase recruitment were sequentially implemented. MEASUREMENTS AND MAIN RESULTS: The baseline enrollment rate was 2.1 subjects/mo, which increased following the single-site introduction of real-time patient screening using an online dashboard (4.5 subjects/mo), deferred consenting (5.2 subjects/mo), and weekend screening (6.1 subjects/mo). However, the subsequent addition of three new study sites was the greatest accelerator of enrollment (21 subjects/mo), representing a 10-fold increase from baseline (p < 0.0001). CONCLUSIONS: Identifying barriers to recruitment and implementing creative strategies to increase recruitment can successfully increase enrollment rates in the challenging ICU environment. PMID- 26825046 TI - The Importance of Mortality Risk Assessment: Validation of the Pediatric Index of Mortality 3 Score. AB - OBJECTIVE: To evaluate the performance of the newest version of the Pediatric Index of Mortality 3 score and compare it with the Pediatric Index of Mortality 2 in a multicenter national cohort of children admitted to PICU. DESIGN: Retrospective, prospective cohort study. SETTING: Seventeen Italian PICUs. PATIENTS: All children 0 to 15 years old admitted in PICU from January 2010 to October 2014. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Eleven thousand one hundred nine children were enrolled in the study. The mean Pediatric Index of Mortality 2 and 3 values of 4.9 and 3.9, respectively, differed significantly (p < 0.05). Overall mortality rate was 3.9%, and the standardized mortality ratio was 0.80 for Pediatric Index of Mortality 2 and 0.98 for Pediatric Index of Mortality 3 (p < 0.05). The area under the curve of the receiver operating characteristic curves was similar for Pediatric Index of Mortality 2 and Pediatric Index of Mortality 3. The Hosmer-Lemeshow test was not significant for Pediatric Index of Mortality 3 (p = 0.21) but was highly significant for Pediatric Index of Mortality 2 (p < 0.001), which overestimated death mainly in high-risk categories. CONCLUSIONS: Mortality indices require validation in each country where it is used. The new Pediatric Index of Mortality 3 score performed well in an Italian population. Both calibration and discrimination were appropriate, and the score more accurately predicted the mortality risk than Pediatric Index of Mortality 2. PMID- 26825047 TI - Decreased interleukin-21 expression in skin and blood in advanced mycosis fungoides. AB - Interleukin (IL)-21 is regarded as a potent antitumor agent, which increases the cytotoxicity of both natural killer (NK) and CD8(+) T cells. In this study, we investigated the role of IL-21 in mycosis fungoides (MF). IL-21 mRNA expression levels in patch and plaque MF were significantly higher than those in normal skin. IL-21 mRNA expression levels in tumor MF were significantly decreased compared with those in patch and plaque MF. Interestingly, mRNA expression levels of IL-21 in MF lesional skin significantly correlated with those of T-helper type 1 cytokines/chemokines such as CXCL10, CXCL11 and gamma-interferon. Immunohistochemistry showed that IL-21 was expressed by keratinocytes in patch and plaque MF. Furthermore, serum IL-21 levels in patients with tumor MF were significantly lower than those of healthy controls and plaque MF. Thus, IL-21 expression was significantly downregulated in skin and blood of patients with tumor MF, which may contribute to progression of MF. Our study suggests that recombinant IL-21 would be a promising therapy for MF. PMID- 26825048 TI - Does hydration status affect MRI measures of brain volume or water content? AB - PURPOSE: To determine whether differences in hydration state, which could arise from routine clinical procedures such as overnight fasting, affect brain total water content (TWC) and brain volume measured with magnetic resonance imaging (MRI). MATERIALS AND METHODS: Twenty healthy volunteers were scanned with a 3T MR scanner four times: day 1, baseline scan; day 2, hydrated scan after consuming 3L of water over 12 hours; day 3, dehydrated scan after overnight fasting of 9 hours, followed by another scan 1 hour later for reproducibility. The following MRI data were collected: T2 relaxation (for TWC measurement), inversion recovery (for T1 measurement), and 3D T1 -weighted (for brain volumes). Body weight and urine specific gravity were also measured. TWC was calculated by fitting the T2 relaxation data with a nonnegative least-squares algorithm, with corrections for T1 relaxation and image signal inhomogeneity and normalization to ventricular cerebrospinal fluid. Brain volume changes were measured using SIENA. TWC means were calculated within 14 tissue regions. RESULTS: Despite indications of dehydration as demonstrated by increases in urine specific gravity (P = 0.03) and decreases in body weight (P = 0.001) between hydrated and dehydrated scans, there was no measurable change in TWC (within any brain region) or brain volume between hydration states. CONCLUSION: We demonstrate that within a range of physiologic conditions commonly encountered in routine clinical scans (no pretreatment with hydration, well hydrated before MRI, and overnight fasting), brain TWC and brain volumes are not substantially affected in a healthy control cohort. J. Magn. Reson. Imaging 2016;44:296-304. PMID- 26825049 TI - Sex differences in spatial cognition: advancing the conversation. AB - The existence of a sex difference in spatial thinking, notably on tasks involving mental rotation, has been a topic of considerable research and debate. We review this literature, with a particular focus on the development of this sex difference, and consider four key questions: (1) When does the sex difference emerge developmentally and does the magnitude of this difference change across development? (2) What are the biological and environmental factors that contribute to sex differences in spatial skill and how might they interact? (3) How malleable are spatial skills, and is the sex difference reduced as a result of training? and (4) Does 'spatializing' the curriculum raise the level of spatial thinking in all students and hold promise for increasing and diversifying the STEM pipeline? Throughout the review, we consider promising avenues for future research. PMID- 26825050 TI - Reduced adaptability, but no fundamental disruption, of norm-based face coding following early visual deprivation from congenital cataracts. AB - Faces are adaptively coded relative to visual norms that are updated by experience, and this adaptive coding is linked to face recognition ability. Here we investigated whether adaptive coding of faces is disrupted in individuals (adolescents and adults) who experience face recognition difficulties following visual deprivation from congenital cataracts in infancy. We measured adaptive coding using face identity aftereffects, where smaller aftereffects indicate less adaptive updating of face-coding mechanisms by experience. We also examined whether the aftereffects increase with adaptor identity strength, consistent with norm-based coding of identity, as in typical populations, or whether they show a different pattern indicating some more fundamental disruption of face-coding mechanisms. Cataract-reversal patients showed significantly smaller face identity aftereffects than did controls (Experiments 1 and 2). However, their aftereffects increased significantly with adaptor strength, consistent with norm-based coding (Experiment 2). Thus we found reduced adaptability but no fundamental disruption of norm-based face-coding mechanisms in cataract-reversal patients. Our results suggest that early visual experience is important for the normal development of adaptive face-coding mechanisms. PMID- 26825051 TI - Epidemiology of dental caries among adolescents in Tamil Nadu, India. AB - OBJECTIVE: Economic and dietary changes in the Indian state of Tamil Nadu have led to compromised oral health status of the adolescent population. Adequate epidemiological data are not available to address the prevention or treatment needs in this region of India. The aim of this study was to measure the prevalence and severity of dental caries among adolescents of Tamil Nadu, a southern state of India. METHODS: The study sample included 974 adolescent school students (12-15 years of age) from both rural and urban areas of Tamil Nadu, India. The decayed, missing and filled teeth (DMFT) index of these students was measured using the World Health Organization oral health survey method, in a quantitative cross-sectional study. RESULTS: The oral health survey indicated that the prevalence of dental caries among adolescents in rural and urban areas of Tamil Nadu was 61.4%, with an average DMFT score of 2.03. Multiple regression analyses indicated factors such as gender, mother's education, type of school and caste as significant predictors of dental caries. CONCLUSION: Female gender, Scheduled Caste and Tribes attending public schools in rural areas were identified as the more vulnerable populations to be affected by dental caries. Oral health policies should be targeted to these adolescent populations in the Tamil Nadu region. PMID- 26825052 TI - In situ plasma fabrication of ceramic-like structure on polymeric implant with enhanced surface hardness, cytocompatibility and antibacterial capability. AB - Polymeric materials are commonly found in orthopedic implants due to their unique mechanical properties and biocompatibility but the poor surface hardness and bacterial infection hamper many biomedical applications. In this study, a ceramic like surface structure doped with silver is produced by successive plasma implantation of silicon (Si) and silver (Ag) into the polyamine 66 (PA66) substrate. Not only the surface hardness and elastic modulus are greatly enhanced due to the partial surface carbonization and the ceramic-like structure produced by the reaction between energetic Si and the carbon chain of PA66, but also the antibacterial activity is improved because of the combined effects rendered by Ag and SiC structure. Furthermore, the modified materials which exhibit good cytocompatibility upregulate bone-related genes and proteins expressions of the contacted bone mesenchymal stem cells (BMSCs). For the first time, it explores out that BMSCs osteogenesis on the antibacterial ceramic-like structure is mediated via the iNOS and nNOS signal pathways. The results reveal that in situ plasma fabrication of an antibacterial ceramic-like structure can endow PA66 with excellent surface hardness, cytocompatibility, as well as antibacterial capability. PMID- 26825053 TI - Reducing the burden of diarrhea among children under five years old: lessons learned from oral rehydration therapy corner program implementation in Northern Nigeria. AB - BACKGROUND: In Nigeria, diarrhea remains one of the leading causes of death among children under five years old. Oral Rehydration Therapy (ORT) corners were introduced to health facilities in Bauchi and Sokoto states to serve as points of treatment for sick children and equip caregivers with necessary skills in case management of diarrhea and diarrhea prevention. OBJECTIVES: The operations research study examined the effect of facility-based ORT corners on caregivers' knowledge and skills in management of simple and moderate diarrhea at home, as well as caregivers' and service providers' perceived facilitators and barriers to utilization and delivering of ORT corner services. It also examined whether ORT activities were conducted according to the established protocols. METHODS: This quantitative study relied on multiple sources of information to provide a complete picture of the current status of ORT corner services, namely surveys with ORT corner providers (N = 21), health facility providers (N = 23) and caregivers (N = 229), as well as a review of service statistics and health facility observations. Frequency distribution and binary analysis were conducted. RESULTS: The study revealed that ORT corner users were more knowledgeable in diarrhea prevention and management and demonstrated better skills for managing diarrhea at home than ORT corner non-users. However, the percentage of knowledgeable ORT users is not optimal, and providers need to continue to work toward improving such knowledge. ORT corner providers identified a lack of supplies as the major barrier for providing services. Furthermore, the study revealed a lack of information, education and communication materials, supportive supervision, and protocols and guidelines for delivering ORT corner services, as well as inadequate documentation of services provided at ORT corners. RECOMMENDATIONS: Recommendations for ORT corners program planners and implementers include ensuring all ORT corners have oral rehydration salt (ORS) packages and salt, sugar, and zinc tablets in stock, a secured commodity supply chain to avoid stockouts, and adequate policies and procedures in place. PMID- 26825054 TI - Groundwater arsenic and education attainment in Bangladesh. AB - BACKGROUND: Thousands of groundwater tube wells serving millions of Bangladeshis are arsenic contaminated. This study investigates the effect of these wells on the education attainment and school attendance of youths who rely on those wells for drinking water. METHODS: The analysis combines data from the 2006 Bangladesh Multiple Indicator Cluster Survey (2006 MICS) and the National Hydrochemical Survey (NHS) of Bangladeshi tube wells' contamination conducted between 1998 and 2000. The study uses multiple regression analysis to estimate the differences in education attainment and school attendance among the following: (i) youths who live where tube wells are safe, (ii) youths who live where tube wells are unsafe but who report drinking from an arsenic-free source, and (iii) youths who live where tube wells are unsafe but who do not report drinking from an arsenic-free source. RESULTS: Controlling for other determinants of education attainment and school attendance, young Bangladeshi males who live where tube wells are unsafe (by Bangladeshis standards) but who report drinking from arsenic-free sources are found to have the same education attainment (among 19- to 21-year-olds) and school attendance (among 6- to 10-year-olds), on average, as corresponding young Bangladeshi males who live where wells are safe. But young Bangladeshi males who live where tube wells are unsafe and who do not report drinking from an arsenic free source attain, on average, a half-year less education (among 19- to 21-year olds) and attend school, on average, five to seven fewer days a year (among 6- to 10-year-olds) than do other Bagladeshi males of those ages. The estimated effects for females are of the same sign but much smaller in magnitude. CONCLUSION: Bangladeshi public health measures to shift drinking from unsafe to safe wells not only advance good health but also increase males' education attainment. PMID- 26825055 TI - Low anterior resection syndrome: a survey of the members of the American Society of Colon and Rectal Surgeons (ASCRS), the Spanish Association of Surgeons (AEC), and the Spanish Society of Coloproctology (AECP). AB - BACKGROUND: Low anterior resection syndrome (LARS) is frequent following sphincter-sparing procedures for rectal cancer. OBJECTIVE: This study aims to assess surgeons' awareness of LARS. DESIGN: This was a survey study. SETTINGS: Members of the American Society of Colon and Rectal Surgeons (ASCRS), the Spanish Association of Surgeons (AEC), and the Spanish Society of Coloproctology (AECP). PARTICIPANTS: Three hundred thirty-four surgeons from the ASCRS and 150 from the Spanish Societies completed a 23-item electronic questionnaire. MAIN OUTCOME MEASURES: Surgeons' opinions regarding different aspects of LARS. RESULTS: The proportion of rectal cancer patients undergoing sphincter-sparing operations ranged between 71 and 90 %. Low anterior resection with end-to-end anastomosis was the most frequently cited procedure after mesorectal excision. More than 80 % of participants were recognized to be moderately or extremely aware of the condition, but regarding the method used to assess LARS, the majority relied on clinical manifestations. Around 35 % of surgeons considered that severe LARS developed in less than 40 % of patients. The most important factor related to defecatory function impairment in the surgeons' opinion was the distance from the anal margin to anastomosis. Other factors thought to be involved were anastomotic leakage, preoperative radiation therapy, age, and postoperative radiotherapy, with similar percentages in the two groups of surgeons. Lifestyle changes and dietary measures associated with or without drug treatment was the modality of choice. The experience with transanal irrigation or sacral nerve stimulation was limited. It was considered that <30 % of patients chronically suffer from severe LARS with significant quality of life impairment. LIMITATIONS: The limitations of this study are the international mix and expert status of the specialists. CONCLUSIONS: The probability of patients suffering from LARS was underestimated despite reporting good knowledge of the syndrome. Validated methods for the assessment of LARS were rarely used. Deficient awareness regarding risk factors for LARS was documented. Knowledge of therapeutic options was also limited. PMID- 26825056 TI - An outbreak of cholera in Medipally village, Andhra Pradesh, India, 2013. AB - BACKGROUND: Cholera continues to remain endemic in over 50 countries and has caused large epidemics with around 3-5 million cases occurring every year in Asia alone. In India, cholera is endemic in many states. However, etiological information and age-specific incidence related to cholera outbreaks is limited. In November 2013, district authorities reported a cluster of diarrheal disease among residents of Medipally to the state surveillance unit. We investigated this cluster to confirm its etiology, describe its magnitude, identify potential risk factors, and make recommendations for control. FINDINGS: A house-to-house active search was conducted to identify cases of acute diarrhea and collect information on drinking water source. Drinking water samples were collected from common water sources and sampled households to test for bacteriological quality. Ten stool samples were collected for culture. A matched case-control study was conducted to identify the risk factors. A total of 138 case-patients of diarrhea (Attack rate: 11.5/100; POPULATION: 15 1,200) and 1 death (Case Fatality Ratio: 0.72/100) were identified. Five of the 10 stool samples were culture positive for V. cholerae, serogroup O1 El Tor. Drinking water from the overhead tank [Adjusted OR (AOR): 31.94, 95% CI: 7.3-139.5] was associated with risk of developing illness. CONCLUSIONS: This outbreak affected nearly 11% of the village population and was due to contamination of the main drinking water source. Outbreaks such as this can be prevented by constructing the drain away from the water pipelines and by monitoring regular chlorination of drinking water source and inspection of pipelines for damage. PMID- 26825057 TI - Complementary alternative medicine use among patients with dengue fever in the hospital setting: a cross-sectional study in Malaysia. AB - BACKGROUND: In Malaysia, the number of reported cases of dengue fever demonstrates an increasing trend. Since dengue fever has no vaccine or antiviral treatment available, it has become a burden. Complementary and alternative medicine (CAM) has become one of the good alternatives to treat the patients with dengue fever. There is limited study on the use of CAM among patients with dengue fever, particularly in hospital settings. This study aims to determine the prevalence, types, reasons, expenditure, and resource of information on CAM use among patients with dengue fever. METHODS: This is a descriptive, cross-sectional study of 306 patients with dengue fever, which was carried out at the dengue clinic of three hospitals. Data were analysed using IBM SPSS Statistics version 21.0 and logistic regression analysis was used to determine the factors associated with CAM use. RESULTS: The prevalence of CAM use was 85.3% among patients with dengue fever. The most popular CAMs were isotonic drinks (85.8%), crab soup (46.7%) and papaya leaf extract (22.2%). The most common reason for CAM use was a good impression of CAM from other CAM users (33.3%). The main resource of information on CAM use among patients with dengue fever was family (54.8%). In multiple logistic regression analysis, dengue fever patients with a tertiary level are more likely to use CAM 5.8 (95% confidence interval (CI 1.62-20.45) and 3.8 (95% CI 1.12-12.93) times than secondary level and primary and below respectively. CONCLUSION: CAM was commonly used by patients with dengue fever. The predictor of CAM use was a higher level of education. PMID- 26825058 TI - High prevalence of typhoidal Salmonella enterica serovars excreting food handlers in Karachi-Pakistan: a probable factor for regional typhoid endemicity. AB - BACKGROUND: Typhoid fever is the persistent cause of morbidity worldwide. Salmonella enterica serovar's carriers among food handlers have the potential to disseminate this infection on large scale in the community. The purpose of this study was to determine the prevalence of typhoidal S. enterica serovars among food handlers of Karachi. METHODS: This cross-sectional study was conducted in Karachi metropolis. A total of 220 food handlers were recruited on the basis of inclusion criteria from famous food streets of randomly selected five towns of Karachi. Three consecutive stool samples were collected from each food handler in Carry Blair transport media. Culture, biochemical identification, serotyping, and antimicrobial susceptibility tests for S. enterica serovars were done. RESULTS: Out of 220 food handlers, 209 consented to participate, and among them, 19 (9.1%) were positive for S. enterica serovars. Serotyping of these isolates showed that 9 (4.3%) were typhoidal S. serovars while 10 (4.7%) were non-typhoidal S. serovars. Of the typhoidal S. serovars, 7 were S. enterica serovar Typhi and 1 each of S. enterica serovar Paratyphi A and B. The resistance pattern of these isolates showed that 77.7% were resistant to ampicillin and 11.1% to cotrimoxazole. All typhoidal S. enterica serovar isolates were sensitive to chloramphenicol, ceftriaxone, cefixime, nalidixic acid, and ofloxacin. CONCLUSIONS: Carrier rate of typhoidal S. enterica serovars in food handlers working in different food streets of Karachi is very high. These food handlers might be contributing to the high endemicity of typhoid fever in Karachi, Pakistan. PMID- 26825059 TI - Dietary quality and patterns and non-communicable disease risk of an Indian community in KwaZulu-Natal, South Africa. AB - BACKGROUND: Limited data exist on the South African Indian diet despite their high prevalence of non-communicable diseases. This study attempted to determine the dietary quality and patterns of an Indian population in KwaZulu-Natal with reference to the high prevalence of non-communicable disease METHODS: Two-hundred and-fifty apparently healthy Indians, aged 35-55 years participated in a cross sectional study where diet was assessed using a validated quantitative food frequency questionnaire. Mean intakes were compared to the World Health Organization goals. Dietary quality was determined by index construction and dietary patterns by factor analysis. RESULTS: The mean daily percentage of energy (%E) from n-3 fatty acids (0.24 %E), dietary fibre (18.4 g/day) and fruit and vegetable intakes (229.4 g/day) were below the World Health Organization goals. Total fat (36.1 %E), polyunsaturated fatty acids (11.8 %E), n-6 fatty acids (11 %E) and free sugars (12.5 %E) exceeded the goals. The means for the deficient index reflected a moderate diet quality whereas, the excess index reflected good diet quality. The Pearson partial correlation coefficients between the deficient index and risk markers were weak whilst, the excess index was inversely correlated with waist circumference for the whole sample. Two factors were identified, based on the percentage of fat that contributed to each food group: factor 1 (meat and fish versus legume and cereal pattern), which accounted for added fat through food preparation; and Factor 2 (nuts and seeds versus sugars and visible fat pattern), which accounted for obvious fat. The medians for waist circumference, blood glucose, cholesterol and triglyceride levels showed significant decreasing trends for factor 1 (p < 0.05). The medians for blood glucose and cholesterol showed significant decreasing trends for factor 2 (p < 0.01). CONCLUSION: A shortfall of fruit and vegetable, fibre and n-3 fatty acid intake in the diet is highlighted. When assessing the diet quality and patterns, guidance on the prudent use of added fats may lead to a healthier lifestyle reducing the prevalence of non-communicable diseases. PMID- 26825061 TI - Structural mechanism of GPCR-arrestin interaction: recent breakthroughs. AB - G protein-coupled receptors (GPCRs) are a major membrane receptor family with important physiological and pathological functions. In the classical signaling pathway, ligand-activated GPCRs couple to G proteins, thereby inducing G protein dependent signaling pathways and phosphorylation by G protein-coupled receptor kinases (GRKs). This leads to an interaction with arrestins, which results in GPCR desensitization. Recently, non-classical GPCR signaling pathways, mediated by GPCR-bound arrestins, have been identified. Consequently, arrestins play important roles in GPCR signaling not only with respect to desensitization but also in relation to G protein-independent signal transduction. These findings have led to efforts to develop functionally biased (i.e. signal transduction biased) GPCR-targeting drugs. One of these efforts is aimed at understanding the structural mechanism of functionally biased GPCR signaling, which includes understanding the G protein-selectivity or arrestin-selectivity of GPCRs. This goal has not yet been achieved; however, great progress has been made during the last 3 years toward understanding the structural mechanism of GPCR-mediated arrestin activation. This review will discuss the recent breakthroughs in the conformational understanding of GPCR-arrestin interaction. PMID- 26825060 TI - Measurement of metal bioaccessibility in vegetables to improve human exposure assessments: field study of soil-plant-atmosphere transfers in urban areas, South China. AB - The quality of cultivated consumed vegetables in relation to environmental pollution is a crucial issue for urban and peri-urban areas, which host the majority of people at the global scale. In order to evaluate the fate of metals in urban soil-plant-atmosphere systems and their consequences on human exposure, a field study was conducted at two different sites near a waste incinerator (site A) and a highway (site B). Metal concentrations were measured in the soil, settled atmospheric particulate matter (PM) and vegetables. A risk assessment was performed using both total and bioaccessible metal concentrations in vegetables. Total metal concentrations in PM were (mg kg-1): (site A) 417 Cr, 354 Cu, 931 Zn, 6.3 Cd and 168 Pb; (site B) 145 Cr, 444 Cu, 3289 Zn, 2.9 Cd and 396 Pb. Several total soil Cd and Pb concentrations exceeded China's Environmental Quality Standards. At both sites, there was significant metal enrichment from the atmosphere to the leafy vegetables (correlation between Pb concentrations in PM and leaves: r = 0.52, p < 0.05) which depended on the plant species. Total Cr, Cd and Pb concentrations in vegetables were therefore above or just under the maximum limit levels for foodstuffs according to Chinese and European Commission regulations. High metal bioaccessibility in the vegetables (60-79 %, with maximum value for Cd) was also observed. The bioaccessible hazard index was only above 1 for site B, due to moderate Pb and Cd pollution from the highway. In contrast, site A was considered as relatively safe for urban agriculture. PMID- 26825062 TI - [Erratum to: Pitfalls in mechanical recanalization]. PMID- 26825063 TI - [Imaging of the head and neck region]. AB - Tumors of the head and neck are predominantly squamous cell carcinomas and those of the salivary glands are predominantly adenocarcinomas, adenoid cystic carcinomas and mucoepidermoid carcinomas. In 2011 the incidence of tumors of the oral cavity and pharynx in Germany was 6839 (5026 male and 1813 female) and of the larynx 1878 (1642 male and 236 female). The incidence of tumors of the nose and paranasal sinuses (467) and salivary glands (470) were much lower ( www.krebsdaten.de/abfrage ). The primary aim of imaging in head and neck cancer is staging of the disease and a precise assessment of tumor invasion. This information is essential for therapy decision-making (i. e. surgery or radiochemotherapy), planning of the extent of resection and subsequent reconstructive measures and also estimation of functional deficits after therapy. Computed tomography (CT) and magnetic resonance imaging (MRI) are the imaging modalities of choice but both have specific advantages and disadvantages. In certain cases both CT and MRI need to be performed for accurate treatment planning. PMID- 26825064 TI - Osteopetrosis in two siblings: two case reports. AB - BACKGROUND: Osteopetrosis is a rare inherited metabolic bone disorder characterized by extensive sclerosis of skeletons, visual and hearing impairment, hepatosplenomegaly and anemia. It has two major clinical forms: the autosomal dominant adult (benign) form is associated with milder symptoms often appearing in later childhood and adulthood whereas the autosomal recessive infantile (malignant) form has severe presentations appearing in very early childhood, if untreated, is typically fatal during infancy or early childhood. A rare autosomal recessive (intermediate) form is present during childhood with some signs and symptoms of malignant osteopetrosis. Diagnosis is mainly based on clinical and typical generalized increase in bone density. CASE PRESENTATION: The two siblings of Indo-Aryan ethnicity, aged five and 8 years, were admitted with irregular low grade fever and gradually increasing abdominal mass for last 3 years. They also had history of hearing loss. On examination, the patients were found pale with poor nutritional status, short stature, frontal bossing and splenomegaly. We made a clinical diagnosis of hemolytic anemia and investigated accordingly. Peripheral Blood Smear was suggestive of leucoerythroblastic picture in both the siblings. We extended our investigations and radiological survey revealed generalized increase in bone density which was consistent with osteopetrosis. CONCLUSION: Osteopetrosis is a rare disease transmitted by autosomal dominant or recessive inheritance having variable penetrance. We report here milder form of disease in the two siblings having typical clinical features in the form of anemia, hepatosplenomegaly and hearing loss. Diagnosis was confirmed by typical generalized increase in bone density in both the patients. PMID- 26825065 TI - Treatment of patients with juvenile idiopathic arthritis (JIA) in a population based cohort. AB - A population-based cohort was utilized to evaluate medications and intra articular injection utilization for patients with juvenile idiopathic arthritis (JIA) to inform clinical practice and further research. In a geographically defined population, all incident cases of JIA cases were identified between January 1, 1994 and December 31, 2013 based first on diagnosis code followed by medical chart confirmation. Medications and intra-articular glucocorticoid injections were abstracted. Predictors of the first disease-modifying antirheumatic drug (DMARD)/biologic and injections were reported as a hazard ratio (HR) with 95 % confidence intervals (CIs) adjusted for age and sex. Kaplan Meier methods evaluated therapy at 6 months and 1 year. Injections were reported per 100 person-years (py) with 95 % CI using the Poisson methods. Seventy-one incident cases were identified. Forty-two (59 %) were female with mean age (standard deviation) at diagnosis of 8.2 (5.3) years. Twenty-six (37 %) utilized at least one DMARD or biologic, in which 77 % of these were prescribed in the first 6 months. Subtype of JIA was significantly associated with DMARDs/biologics (p < 0.001). Intra-articular injections were performed in 48 %. The rate of intra articular injections was 20.7 per 100 py (95 % CI 16.5, 25.6). The rate of joint injections was higher in the first year after diagnosis (p < 0.001) and more common in recent years (p < 0.001). The majority of patients with JIA in a modern population-based cohort do not require DMARDs or biologics. In those who do, the majority receives these within the first 6 months. Intra-articular injections were utilized in almost half of patients with JIA and were increasingly used. PMID- 26825066 TI - Nitazoxanide Analogues as Antimicrobial Agents Against Nosocomial Pathogens. AB - BACKGROUND: The frequent use of antibacterial agents and the exposure of the patients to lifesaving intervention processes are consistently associated with the increased chance of nosocomial infections and the emergence of multidrug resistant microorganisms in the hospital environment. Thus, new antimicrobial agents are of unmet need to treat the severe nosocomial infections caused by these putative pathogens resistant to currently available agents. METHOD: Design, synthesis, and biological evaluation of analogues of nitazoxanide (NTZ), an FDA approved thiazolide antiparasitic, as new antimicrobial agents against nosocomial pathogens were described. The NTZ analogues were rationally explored on the basis of either increasing the electronic resonance effects at the nitrothiazolide moiety or improving the anionic form of the whole NTZ structure. RESULTS: The MICs and MBCs values of these NTZ analogues against prevalent nosocomial pathogens were measured. The benzologous analogues 3a and 4a and p chlorobenzenesulfonamides 8d and 9d exhibited tremendous antimicrobial activities, which were 100- to 2000-fold more potent than NTZ and ciprofloxacin. CONCLUSION: The results demonstrated that delicate manipulation of the NTZ core structure could lead to promising antimicrobial agents against the nosocomial pathogens. PMID- 26825067 TI - Synthesis, in vivo Anticoagulant Evaluation and Molecular Docking Studies of Bicoumarins Obtained from Furocoumarin Peucedanin. AB - BACKGROUND: Synthesis of 7,7.-linked bicoumarins, 3,3.-linked bi(2 isopropyl)psoralens as well as 1H-1,2,3-triazole linked coumarin-2,3 dihydrofurocoumarin and furocoumarin-2,3-dihydrofurocoumarin hybrids was performed by two alternative pathways, either involving a catalyzed transformations of the ethynyl derivatives of plant coumarins - peucedanin or peuruthenicin. OBJECTIVE AND METHODS: The Sonogashira reaction of 7-ethynyl coumarins or 3-ethynyl-2-isopropylpsoralen with the subsequent coumarin triflates led to 7,7'-linked bicoumarins or 3,3'-linked bipsoralens. 1,2,3-Triazole linked coumarin-2,3-dihydrofurocoumarin or furocoumarin-2,3-dihydrofurocoumarin hybrids were synthesized by a regioselective Cu-catalyzed cycloaddition reaction of 2 azidooreoselone with 7-alkynylcoumarins or 3-ethynyl-2-isopropylpsoralen. RESULTS: Pharmacological screening of synthesized bicoumarins for anticoagulant activity in vivo revealed that coumarin-dihydrofurocoumarin hybrids linked with a 1,2,3-triazole ring 20 and 22 were the most active compounds. The presented prothrombin time (PT) values comparable to the reference drug warfarin in a dose 100 mg/kg. Docking studies were undertaken to gain insight into the possible binding mode of these compounds with the coagulation factor Xa (FXa) binding site. CONCLUSION: The moderate toxicity of compounds 20 and 22 (LD50 valuewas more than 3000 mg/kg) encouraged the further design of therapeutically relevant analogues based on these novel type of coumarin hybrids. PMID- 26825069 TI - Preliminary Studies on the Activity of Mixed Polyphenol-Heterocyclic Systems Against B16-F10 Melanoma Cancer Cells. AB - The Bcl-2 family includes 26 proteins involved in apoptosis. Cancer cells can develop the ability to avoid apoptosis through the upregulation and/or down regulation of such proteins Bax, Bcl-xL or Mcl-1, especially during chemoresistance progress. These proteins engaged in a network of dynamic interactions that control apoptosis triggering have become attractive therapeutic targets in cancers including melanoma. Among them, the Bax/Bcl-xL interaction appears critical in maintaining mitochondria integrity. Therefore a series of mixed polyphenol-heterocyclic molecules, were rationally designed by molecular docking as Bax/Bcl-xL inhibitors. It has been screened against B16-F10 melanoma cancer cells for a preliminary investigation of their cytotoxicity. All these compounds exhibited a significant cytotoxicity against these cancer cells, in the 0.3-6 .M range. A pyrazole-type molecule, which had a submicromolar IC50 value with an excellent selectivity index (14), is the most promising derivative for further development. PMID- 26825068 TI - Biologically Active New N, N', N''-Tri-Substituted Ferrocenyl Phenylguanidines and their Characterization. AB - BACKGROUND: Introducing new candidates for various biological targets is a prime characteristic of the present day medicinal research and development. Guanidines are the important bioactive compounds and are well recognized for their diverse biological activities, especially as anticancer, antimicrobial and antioxidant agents. Due to the favorable electronic properties of ferrocene like lipophilicity, redox activity, stability in solution state and its easy derivatization, have made ferrocenyl compounds very popular molecules for biological uses. OBJECTIVES: Keeping in sight, it is valuable to synthesize ferrocenyl guanidines to increase the binding potency with DNA, make them redox active and more lipophilic compounds. METHODS: Six new ferrocenyl phenylguanidines (F1 - F6) have been synthesized via multi step protocol. The structures of F1 - F6 were established by using elemental analysis, UV-visible, multinuclear (1H and 13C) NMR and FTIR spectroscopy. Solution phase redox behavior, of the synthesized compounds, has been characterized by cyclic voltammetry. Two compounds (F2 & F4) were characterized by single crystal XRD. RESULTS: Due to the biological importance of guanidines; these ferrocenyl guanidiens were screened for different biological activities like antibacterial, antifungal, antioxidant and DNA binding. DNA interaction study was done by using UV-visible spectrometry and cyclic voltammetry revealed good binding capacity of the test compounds. CONCLUSION: The results revealed that the ferrocene incorporation to guanidines enhances their DNA binding ability. A similar trend was found in antioxidant and antimicrobial studies. Being the bioactive molecules these compounds are potential drug candidates. PMID- 26825070 TI - Bone turnover and mineral density in adult thalassemic patients: relationships with growth hormone secretory status and circulating somatomedins. AB - Previous evidence supports a role for growth hormone (GH)-insulin-like growth factor (IGF)-I deficiency in the pathophysiology of osteopenia/osteoporosis in adult thalassemia. Moreover, serum IGF-II has never been studied in this clinical condition. Thus, we elected to study the GH secretory status and the levels of circulating somatomedins, correlating these parameters with bone mineral density (BMD) and biochemical markers of bone turnover. A hundred and thirty-nine normal weight adult thalassemic patients (72 men and 67 women) were studied. Lumbar and femoral neck BMD were measured in 106/139 patients. Sixty-eight patients underwent growth hormone releasing hormone plus arginine testing. Measurement of baseline IGF-I and IGF-II was performed in all patients, while osteocalcin, C terminal telopeptide of type I collagen (CTx), and urinary cross-linked N telopeptides of type I collagen (NTx) were assayed in 95 of them. Femoral and lumbar osteoporosis/Z score below the expected range for age were documented in 61.3 and in 56.6 % of patients, respectively. Severe GH deficiency (GHD) was demonstrated in 27.9 % of cases, whereas IGF-I SDS was low in 86.3 %. No thalassemic patients displayed circulating levels of IGF-II below the reference range. GH peaks were positively correlated with femoral, but not lumbar, Z score. No correlations were found between GH peaks and osteocalcin, CTx and NTx. GH peaks were positively correlated with IGF-I values, which in their turn displayed a positive correlation with osteocalcin, CTx, and NTx. No correlations emerged between IGF-I values and either femoral or lumbar Z scores. No correlations were found between IGF-II and any of the following parameters: GH peaks, osteocalcin, CTx, NTx, femoral Z score, and lumbar Z score. Our study, besides providing for the first time evidence of a normal IGF-II production in thalassemia, contributes to a better understanding of the involvement of the somatotropin-somatomedin axis in the pathophysiology of bone demineralization in this disease. In particular, the contribution of GHD to femoral osteoporosis appears to be likely mediated by locally produced rather than circulating IGF-I. PMID- 26825071 TI - Cosmetics as endocrine disruptors: are they a health risk? AB - Exposure to chemicals from different sources in everyday life is widespread; one such source is the wide range of products listed under the title "cosmetics", including the different types of popular and widely-advertised sunscreens. Women are encouraged through advertising to buy into the myth of everlasting youth, and one of the most alarming consequences is in utero exposure to chemicals. The main route of exposure is the skin, but the main endpoint of exposure is endocrine disruption. This is due to many substances in cosmetics and sunscreens that have endocrine active properties which affect reproductive health but which also have other endpoints, such as cancer. Reducing the exposure to endocrine disruptors is framed not only in the context of the reduction of health risks, but is also significant against the background and rise of ethical consumerism, and the responsibility of the cosmetics industry in this respect. Although some plants show endocrine-disrupting activity, the use of well-selected natural products might reduce the use of synthetic chemicals. Instruments dealing with this problem include life-cycle analysis, eco-design, and green labels; in combination with the committed use of environmental management systems, they contribute to "corporate social responsibility". PMID- 26825073 TI - Polycystic ovary syndrome (PCOS) and endocrine disrupting chemicals (EDCs). AB - Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of unclear etiopathogenesis that is likely to involve genetic and environmental components synergistically contributing to its phenotypic expression. Endocrine disrupting chemicals (EDCs) and in particular Bisphenol A (BPA) represent a group of widespread pollutants intensively investigated as possible environmental contributors to PCOS pathogenesis. Substantial evidence from in vitro and animal studies incriminates endocrine disruptors in the induction of reproductive and metabolic aberrations resembling PCOS characteristics. In humans, elevated BPA concentrations are observed in adolescents and adult PCOS women compared to reproductively healthy ones and are positively correlated with hyperandrogenemia, implying a potential role of the chemical in PCOS pathophysiology, although a causal interference cannot yet be established. It is plausible that developmental exposure to specific EDCs could permanently alter neuroendocrine, reproductive and metabolic regulation favoring PCOS development in genetically predisposed individuals or it could accelerate and/or exacerbate the natural course of the syndrome throughout life cycle exposure. PMID- 26825072 TI - Thyroid nodules and thyroid autoimmunity in the context of environmental pollution. AB - Evidence suggests that in most industrialized countries autoimmune disorders, including chronic lymphocytic thyroiditis, are increasing. This increase parallels the one regarding differentiated thyroid cancer, the increment of which is mainly due to the papillary histotype. A number of studies have pointed to an association between chronic lymphocytic thyroiditis and differentiated thyroid cancer. The upward trend of these two thyroid diseases is sustained by certain environmental factors, such as polluting substances acting as endocrine disrupting chemicals. Herein we will review the experimental and clinical literature that highlights the effects of environmental and occupational exposure to polluting chemicals in the development of autoimmune thyroid disease or differentiated thyroid cancer. Stakeholders, starting from policymarkers, should become more sensitive to the consequences for the thyroid resulting from exposure to EDC. Indeed, the economic burden resulting from such consequences has not been quantified thus far. PMID- 26825074 TI - Ten years of experience in endovascular treatment of ruptured aneurysms of the posterior inferior cerebellar artery. AB - BACKGROUND: The aim of this study is to present our 10 years of experience in endovascular treatment of ruptured posterior inferior cerebellar artery (PICA) saccular aneurysms and to compare clinical presentation and outcome after endovascular treatment between patients with PICA aneurysms and patients with aneurysms in different locations. METHODS AND FINDINGS: Out of 932 patients with a ruptured intracranial aneurysm treated endovascularly in our institution, 38 aneurysms were located at the posterior inferior cerebellar artery. Clinical presentation, mean aneurysm diameter and outcome of the therapy in this group were compared with the same for ruptured aneurysms in other locations. Patients discharged with favourable outcomes were checked angiographically in the follow up period. Thirty-four patients with ruptured PICA aneurysms were treated by selective endovascular coiling. Two patients with wide-necked aneurysms had endovascular stents implanted. In two cases, the parent vessel was occluded due to failure to catheterise the target aneurysm. The evaluated variables did not differ significantly between two groups, but significantly more ruptured aneurysms in the PICA group were under 6 mm in diameter. 29.4% of controlled aneurysms needed additional reembolisation in the follow-up period. CONCLUSIONS: Clinical presentation, extension of subarachnoid haemorrhage and outcome after endovascular treatment did not differ significantly between patients with ruptured aneurysms located on the PICA and patients with aneurysms located elsewhere intracranially. Endovascular treatment is an effective method of therapy in patients with ruptured PICA aneurysms. In our experience, even when sacrificing of the PICA is required, the results of treatment are favourable. PMID- 26825075 TI - Necrotizing fasciitis due to Vibrio cholerae non-O1/non-O139 after exposure to Austrian bathing sites. AB - We report on two cases of necrotizing fasciitis of the lower leg due to nontoxigenic Vibrio cholerae (V. cholerae). A 73-year-old woman (case 1) and an 80-year-old man (case 2) were hospitalized with symptoms of necrotizing fasciitis on July 18 and August 15, 2015, respectively. In both cases, symptoms started the day after swimming in local ponds. Swabs gained intraoperatively and a blood culture from the male patient, yielded V. cholerae non-O1/non-O139, negative for cholera toxin gene ctx and positive for hemolysin genes hlyA and hlyB. Water samples taken from pond A on August 17, 2015 (32 days after exposure of case 1) and from pond B on August 20, 2015 (7 days after exposure of case 2) yielded non O1/non-O139 V. cholerae in most-probable numbers of > 11,000 per 100 ml each. The occurrence of two cases of necrotizing fasciitis within a 1 month period related to two Austrian non-saline bathing waters, previously not known to harbor V. cholerae, is probably linked to the prevailing extreme weather conditions (heat wave, drought) this summer in Austria. While case 1 was discharged in good clinical condition after 73 days, case 2 died after four months of hospitalization. Public health authorities are challenged to assess the effects of long-term climate change on pathogen growth and survival in continental bodies of fresh water. PMID- 26825076 TI - Genotoxic investigation of a thiazolidinedione PPARgamma agonist using the in vitro micronucleus test and the in vivo homozygotization assay. AB - Pioglitazone (PTZ) is an oral antidiabetic agent whose anti-cancer properties have been described recently. Since PTZ increases the production of reactive oxygen species in mammalian cells, the aim of current study was to evaluate the cytotoxic, mutagenic and recombinogenic effects of PTZ using respectively the in vitro mitotic index assay and the in vitro mammalian cell micronucleus test in human peripheral lymphocytes, and the in vivo homozygotization assay in Aspergillus nidulans, which detects the loss of heterozygosity due to somatic recombination. Although the lowest PTZ concentrations (4-36 MUM) did not show any significant rise in the micronucleus production, the higher PTZ concentration (108 MUM) produced a statistically higher number of micronuclei than the negative control and significantly altered the cell-proliferation kinetics, demonstrating the mutagenic and antiproliferative effects of PTZ, respectively. The recombinogenic activity of PTZ, demonstrated here for the first time, was observed at the highest tested concentration (400 MUM) through the homozygotization index rates significantly different from the negative control. Taken together, our results show that PTZ is genotoxic at a concentration higher than the therapeutic plasma concentration. This PTZ genotoxicity may be a potential benefit to its previously described antitumour activity. PMID- 26825077 TI - Transmission of the Aegilops ovata chromosomes carrying gametocidal factors in hexaploid triticale (*Triticosecale Wittm.) hybrids. AB - The main aim of this work was to induce the chromosome rearrangements between Aegilops ovata (UUMM) and hexaploid triticale (AABBRR) by expression of the gametocidal factor located on the chromosome 4M. The Aegilops ovata * Secale cereale (UUMMRR) amphiploids and triticale 'Moreno' were used to produce hybrids by reciprocal crosses. Chromosome dynamics was observed in subsequent generations of hybrids during mitotic metaphase of root meristems and first metaphase of meiosis of pollen mother cells. Chromosomes were identified by genomic in situ hybridisation (GISH) and fluorescence in situ hybridisation (FISH) using pTa71, pTa791, pSc119.2 and pAs1 DNA probes. It has been shown that the origin of the genetic background had an influence on Aegilops chromosome transmission. Moreover, it has been reported that the preferential transmission of chromosome 4M appeared during both androgenesis and gynogenesis. It is also hypothesised that the expression of the triticale Gc gene suppressor had an influence on the semi-fertility of hybrids but did not inhibit the chromosome rearrangements. This paper also describes the double haploid production, which enabled to obtain plants with two identical copies of triticale chromosomes with translocations of Aegilops chromatin segments. PMID- 26825078 TI - Synthesis of 2-Mercaptonicotinic Acid-Capped CdSe Quantum Dots and its Application to Spectrofluorometric Determination of Cr(VI) in Water Samples. AB - The CdSe quantum dots (QDs) capped with 2-mercaptonicotinic acid (H2MN) were prepared through a controllable process at 80 degrees C. The prepared QDs were characterized by XRD, TEM, IR, UV-Vis and fluorescence (FL) techniques. It was found that the QDs were nearly mono-disperse with the diameters in the range of 8 10 nm. These QDs are capable to exhibit strong FL even in concentrated acidic media. They exhibit an enhanced fluorescence in the presence of Cr(VI), which was used for the determination of Cr(VI) in water samples. The linear range was found to be 1 * 10(-7)-6.0 * 10(-6) M with the RSD and DL of 0.92 % and 5 * 10(-8) M, respectively. Except that Ca(2+) and Fe(3+) which can be eliminated through a simple precipitation process, the other co-existent ions present in natural water were not interfered. The recoveries obtained for the added amounts of Cr(VI) were in the range of 96.9-103.2 %, which denote on application of the method, satisfactorily. PMID- 26825080 TI - Xiaoke Pill () and anti-diabetic drugs: A review on clinical evidence of possible herb-drug interactions. AB - OBJECTIVE: To critically analyze the clinically-based evidence of herb-drug interaction on Xiaoke Pill () and its concomitant use with anti-diabetic drugs. METHODS: MEDLINE, EMBASE, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), International Pharmaceutical Abstracts (IPA), Chinese BioMedical Literature Database (CBM), Traditional Chinese Medical Database System (TCMDS), China National Knowledge Infrastructure Database (CNKI) and Wangfang Databases were searched. Levels of Evidence and Severity Level of Interaction were used to evaluate the quality of the included studies. RESULTS: A total of 27 studies published in Chinese, including 2 randomized controlled trials, 3 case series and 22 case reports, were included. Eighteen herbdrug interactions were reported involving Xiaoke Pill as monotherapy, while 6 herb-drug interactions occurred associated with Xiaoke Pill in combination with anti-diabetic drugs. The clinical results of herb-drug interaction of Xiaoke Pill were reported as additive blood glucose-lowering effects with anti-diabetic drugs, including benefifi cial and adverse hypoglycemic effects, anaphylactic shock and severe hair loss. Of these interactions 82.8% were reported to be associated with potential deterioration of the patients' conditions including hypoglycemic coma, stroke, mental disorder and even death. CONCLUSIONS: This review helped establish the clinically-based evidence about herb-drug interaction of Xiaoke Pill and its concomitant use with anti-diabetic drugs. The fifi ndings would help arouse the awareness of both health professionals and the general public to avoid the adverse herb-drug interactions of Xiaoke Pill in healthcare and community settings. PMID- 26825079 TI - Adsorption Kinetics and Binding Studies of Protein Quantum Dots Interaction: A Spectroscopic Approach. AB - Protein Quantum dots interaction is crucial to investigate for better understanding of the biological interactions of QDs. Here in, the model protein Bovine serum albumin (BSA) was used to evaluate the process of protein QDs interaction and adsorption on QDs surface. The modified Stern-Volmer quenching constant (Ka), number of binding sites (n) at different temperatures (298 308 and 318 K +/- 1) and corresponding thermodynamic parameters (DeltaG < 0, DeltaH < 0, and DeltaS > 0) were calculated. The quenching constant (Ks) and number of binding sites (n) is found to be inversely proportional to temperature. It signified that static quenching mechanism is dominant over dynamic quenching. The standard free energy change (DeltaG < 0) implies that the binding process is spontaneous, while the enthalpy change (DeltaH < 0) suggest that the binding of QDs to BSA is an enthalpy-driven process. The standard entropy change (DeltaS > 0) suggest that hydrophobic force played a pivotal role in the interaction process. The adsorption process were assessed and evaluated by pseudofirst-order, pseudosecond-order kinetic model, and intraparticle diffusion model. PMID- 26825081 TI - Synergistic anti-tumor activity and mechanisms of total glycosides from Cimicifuga dahurica in combination with cisplatin. AB - OBJECTIVE: To determine the effect and mechanism of combination treatment of the total glycosides from Cimicifuga dahurica (TGCD) and cisplatin (CDDP) in vitro in human colon cancer cells (HCT-8) and in vivo in mouse hepatoma cells (H22) bearing mice. METHODS: H22 tumor-bearing imprinting control region (ICR) mice were treated with TGCD, CDDP, and TGCD + CDDP for 10 days. Tumor volume and tumor weight were evaluated. TGCD and CDDP in different concentrations were added separately and in combination to cultures of different cancer cell lines, including the HCT-8. Effects of TGCD and CDDP on cell proliferation were detected by 3-(4,5-dimethyl-2-thiazole)-2-5-biphenly-tetrazole bromide (MTT) method and effects on cell apoptosis were tested by flfl ow cytometry and western blotting at 24 h after treatment. RESULTS: Combination index values (CI<0.8) suggested the synergistic effects of the TGCD + CDDP. This combination resulted in the highest increase in the percentage of apoptotic HCT-8 cells, caused cell cycle arrest in G2/M phase and increased expression of cleaved caspase-3, -8, and -9, Bax, phospho-c-Jun N-terminal kinase (p-JNK), and phospho-p38 mitogen-activated protein kinase (p-p38 MAPK), as well as decreased expression of Bcl-2, JNK, p38 MAPK, Poly (ADP-ribose) polymerase 1 (PARP1), caspase-3, and caspase-8 compared with single-agent treated and control groups. TGCD + CDDP treatment reduced tumor weight by 86.1%+/-7.2% compared with 64.5%+/-6.8% by CDDP or 46.9%+/-6.9% by the TGCD alone in vivo. CONCLUSIONS: TGCD enhanced the anticancer activity of CDDP in an additive-to-synergistic manner by activating multiple signaling pathways (including apoptosis). These fifi ndings suggest the potential benefifi t of combined treatment of the TGCD and CDDP against cancer of the colon and liver. PMID- 26825082 TI - Qualitative analysis on a proposal for key specific medical treatment for aplastic anemia. AB - OBJECTIVE: By reviewing the medical treatments for aplastic anemia (AA, Suilao Disease), which is the important research interest of Collaborative Group, Key Department of Blood Disease, State Administration of Chinese medicine, the consensus on the diseases have been reached among the different units of the collaborative group. METHODS: Using qualitative analysis, we determined the characteristics, location and pathogenesis of Suilao disease. We discovered the ways of traditional Chinese medical treatment in curing Suilao disease. RESULTS: Acute AA (acute suilao) and chronic AA (chronic suilao) diseases require different treatment. Acute AA requires 3 phrases of treatments, which are "cold", "warm" and "hot". However, chronic AA requires a dialectic treatment, which involves reinforcement of the Shen (Kidney). Suitable Chinese medical treatments for curing Suilao disease were discussed and reached a consensus. CONCLUSION: It is concluded that a summarized therapy approved by many experts could be widely used. PMID- 26825083 TI - Effects of Electro-Acupuncture at Zusanli, Guanyuan for Sepsis Patients and Its Mechanism through Immune Regulation. AB - OBJECTIVE: To evaluate the effect of electro-acupuncture on Zusanli (ST 36), Guanyuan (RN 4) in patients with sepsis, and explore its mechanism in term of immune regulation. METHODS: In this prospective randomized controlled trial, 60 patients with sepsis were randomly assigned to the control group and the intervention group equally by block randomization. Patients in the control group received routine treatment and those in the intervention group received electro acupuncture at bilateral Zusanli and Guanyuan in addition to routine treatment, respectively. The mortality at 28 days, Acute Physiology and Chronic Health Evaluation (APACHE)-II score were compared to evaluate the effect, and the levels of T cell subsets (CD3+, CD4+, CD8+, CD4+/CD8+) and monocytes of human leukocyte antigen (HLA)-DR using flow cytometry were compared to explore the mechanism of this combined treatment. RESULTS: Fifty-eight patients completed the trial with 29 in each group. There was no significant difference of mortality in the 28th day between the two groups, with 5 death of 29 patients in the intervention group (17.2%) and 9 of 29 in the control group (31.0%). After treatment, APACHE-II score of both groups was significantly decreased, however, score of the intervention group was lower than the control group (13.28+/-7.07 vs. 17.10+/ 5.83; P<0.01). The levels of CD3+, CD4+, CD8+ and CD4+/CD8+ ratio of the intervention group improved after treatment and were higher than the control group (59.71%+/-11.94% vs. 52.54%+/-11.86%; 36.46%+/-7.60% vs. 31.58%+/-10.23%; 18.40%+/-8.82% vs. 23.07%+/-7.30%; 2.38+/-1.14 vs. 1.54+/-0.80, respectively; all P<0.05). The expression of HLA-DR significantly increased after treatment in the intervention group than that in the control group (7.28%+/-9.26% vs. 1.27%+/ 7.00%; P<0.01). CONCLUSION: Electro-acupuncture at Zusanli and Guanyuan could improve clinical curative effect in patients with sepsis, which might be achieved by regulation of the immune system. PMID- 26825085 TI - Effect of Zataria multiflora extract on total and differential white blood cell count and endothelin level in blood of ovalbumin sensitized guinea pigs. AB - OBJECTIVE: To investigate the effect of hydro-ethanolic extract of Zataria multiflfl ora (Z. multiflflora) on endothelin level, total and differential white blood cells (WBC) count of sensitized guinea pigs. METHODS: Five groups of guinea pigs sensitized to ovalbumin (OA) were given drinking water alone (group S), drinking water containing three concentrations of Z. multiflflora (0.2, 0.4 and 0.8 mg/mL as groups S+Z1, S+Z2 and S+Z3) and dexamethasone (group S+D), n=6 for each group. The endothelin levels as well as total and differential WBC count in blood of sensitized and control guinea pigs were evaluated using enzyme linked immunosorbent assay method, and hemocytometer and Wright-Giemsa's staining of blood sample smear respectively. RESULTS: Blood endothelin levels, total and most differential WBC count were increased but lymphocytes decreased in sensitized animals compared to controls (allP <0.01). In groups S+D, S+Z2 and S+Z3 endothelin level, total and differential WBC counts were signifificantly improved compared with group S (P <0.01). Although, all measured parameters in group S+Z1 was lower than group S+D (P <0.01), some parameters in group S+Z3 were greater than in group S+D (P <0.05 toP <0.01). CONCLUSION: The results showed an anti inflflammatory effect of Z. multiflflora extract in sensitized guinea pigs, which may suggest a therapeutic potential for the plant on asthma. PMID- 26825084 TI - Analysis of mutations of two Gitelman syndrome family SLC12A3 genes and proposed treatments using Chinese medicine. AB - OBJECTIVE: To determine the gene location of two Gitelman syndrome (GS) family SLC12A3 genes and explore treatments using Chinese medicine (CM) prescriptions. METHODS: In order to locate the two GS mutations, samples were collected from 11 people from two different pedigrees for direct genetic sequencing and comparison of the 26 exons of SLC12A3. Furthermore, the change of serum potassium was monitored throughout the therapy and those two probands undertook a sequential superposition of Western medicine (including potassium, Panangin and potassium sparing diuretics) with CM prescription based on Buyang Huanwu Decoction () and Sijunzi Decoction (). The treatment included three stages, oral potassium chloride for the first 2 weeks (stage 1), potassium-sparing diuretic and Panangin with potassium chloride for the next 2 weeks (stage 2), CM along with the medicine in stage 2 for the final 2 weeks (stage 3). RESULTS: The three mutations occurring in proband 1 from pedigree I were Thr60Met, 965-1_976del13ins12 (small indels mutation) and Ala122Ala (homozygous silent mutation). Likewise, three mutations, Asn359Lys, Thr382Met and Arg913Gln, appeared in the proband 2 from pedigree II. The serum potassium levels increasing from baseline to sequential stages were 1.63 mmol/L (baseline), 2.5 mmol/L (stage 1), 3.1 mmol/L (stage 2) and 3.9 mmol/L (stage 3) in the proband 1, and 2.8 mmol/L (baseline), 3.1 mmol/L (stage 1), 3.5 mmol/L (stage 2) and 4.3 mmol/L (stage 3) in the proband 2, respectively. The symptoms (numbness of limbs, weakness, palpitations, etc.) of both probands were all alleviated. CONCLUSIONS: The mutations of both GS pedigrees can be defined as compound heterozygous mutations, most of which are known as missense mutations. Applying CM could be an appropriate choice for future intervention of GS. PMID- 26825086 TI - Fetuin-A is Associated to Serum Calcium and AHSG T256S Genotype but Not to Coronary Artery Calcification. AB - Vascular calcification has been recently associated to an increased cardiovascular risk and mortality. In few studies, Fetuin-A showed an association to coronary artery calcification (CAC), although the physiopathological mechanism underlying this association has not been fully established yet. Seventy-four patients with one or more cardiovascular risk factor and asymptomatic for coronary vasculopathy were included in the study. CAC was evaluated by Agatston score. Serum Fetuin-A levels were determined by ELISA. Molecular analysis of AHSG T256S gene variant (rs4918) was performed by PCR-RFLP. Serum Fetuin-A was correlated to serum calcium (r = 0,321; P = 0,018), but not to serum phosphorous. Multivariate linear regression analysis confirmed this association and showed that calcium and AHSG genotype were independent predictors of Fetuin-A (P = 0.037, P = 0.014, respectively). In particular, subjects carrying the SS genotype had lower levels of Fetuin-A and calcium (P = 0.037 and P = 0.038, respectively). When we compare subjects with CAC 0-10 with subjects with CAC > 10, we found that only age and male gender (P < 0.001, P = 0.035, respectively), but not Fetuin-A, were associated to CAC. Fetuin-A is not associated to CAC in subjects with low cardiovascular risk profile and asymptomatic for coronary vasculopathy, suggesting that in this setting Fetuin-A, although correlated to serum levels of calcium, could be not involved in mineral deposition on coronary vessels. PMID- 26825087 TI - Identification of novel microbes associated with pelvic inflammatory disease and infertility. AB - OBJECTIVES: As pelvic inflammatory disease (PID) aetiology is not completely understood, we examined the relationship between select novel bacteria, PID and long-term sequelae. METHODS: Fastidious bacterial vaginosis (BV)-associated bacteria (Sneathia (Leptotrichia) sanguinegens, Sneathia amnionii, Atopobium vaginae and BV-associated bacteria 1 (BVAB1)), as well as Ureaplasma urealyticum and Ureaplasma parvum were identified in cervical and endometrial specimens using organism-specific PCR assays among 545 women enrolled in the PID Evaluation and Clinical Health study. Risk ratios and 95% CIs were constructed to determine associations between bacteria, histologically confirmed endometritis, recurrent PID and infertility, adjusting for age, race, gonorrhoea and chlamydia. Infertility models were additionally adjusted for baseline infertility. RESULTS: Persistent detection of BV-associated bacteria was common (range 58% for A. vaginae to 82% for BVAB1) and elevated the risk for persistent endometritis (RRadj 8.5, 95% CI 1.6 to 44.6) 30 days post-cefoxitin/doxycycline treatment, independent of gonorrhoea and chlamydia. In models adjusted for gonorrhoea and chlamydia, endometrial BV-associated bacteria were associated with recurrent PID (RRadj 4.7, 95% CI 1.7 to 12.8), and women who tested positive in the cervix and/or endometrium were more likely to develop infertility (RRadj 3.4, 95% CI 1.1 to 10.4). Associations between ureaplasmas and PID sequelae were modest. CONCLUSIONS: To our knowledge, this is the first prospective study to demonstrate that S. sanguinegens, S. amnionii, BVAB1 and A. vaginae are associated with PID, failure of the Centers for Disease Control and Prevention-recommended treatment to eliminate short-term endometritis, recurrent PID and infertility. Optimal antibiotic regimens for PID may require coverage of novel BV-associated microbes. PMID- 26825088 TI - Long-Term Cognitive and Functional Outcomes in Children with Mucopolysaccharidosis (MPS)-IH (Hurler Syndrome) Treated with Hematopoietic Cell Transplantation. AB - The long-term cognitive and functional outcomes of children with mucopolysaccharidosis type I (MPS-IH) post-hematopoietic cell transplant (HCT) are not well documented, and the role of genetic and treatment factors in these outcomes has yet to be defined. In this multi-site, international study, we (1) characterize the cognitive and functional status of 47 individuals (ages 2-25, mean of 10.6 years) with MPS-IH who are 1-24 years post HCT (mean = 9 years) and (2) examine contributions of genotype, transplant characteristics, and sociodemographic factors to cognitive ability, adaptive behavior, and quality of life. The overall cognitive ability of our sample was mildly impaired, more than two standard deviations below general population norms. Parent reported adaptive behaviors (i.e., communication, daily living, and motor skills) were similarly impaired with a relative strength in socialization. Quality of life, as reported by parents, fell more than two standard deviations below population norms for physical functioning; however, psychosocial quality of life (emotional well being) approximated population norms. In linear regression analysis, adjusted for demographic and treatment factors, mutation severity was associated with lower cognitive ability (p = 0.005) and adaptive functioning (p = 0.004), but not parent ratings of children's quality of life. Older age at HCT was associated with poorer physical quality of life (p = 0.002); lower socioeconomic status (p = 0.028) and unrelated bone marrow HCT (p = 0.010) were associated with poorer psychosocial quality of life. Implications for screening and early intervention for children at risk for poorer cognitive and functional outcomes are described. PMID- 26825089 TI - First record of the rare species Aeromonas schubertii from mussels: phenotypic and genetic reevaluation of the species and a review of the literature. AB - In a study where the prevalence of Aeromonas in shellfish was analysed, three isolates of Aeromonas schubertii were identified, representing this the first report of this species from mussels. This species was originally described in 1988 from strains isolated from extra-intestinal human infections and since then has been cited in only 18 occasions. For many years, A. schubertii was the only mannitol-negative species of the genus. However, three additional mannitol negative species (Aeromonas simiae, Aeromonas diversa and Aeromonas australiensis) have been described. This, together with the fact that A. schubertii is a rare human pathogenic species, motivated the present study to characterize its biochemical behaviour and differentiation from the other mannitol-negative species. The molecular similarity (16S rRNA, rpoD and gyrB genes) of the strains, presence of virulence genes and antimicrobial resistance were determined. All A. schubertii strains showed the same phenotypic behaviour, i.e. they use citrate, are positive for lysine decarboxylase and DL-lactate, but negative for production of mannitol, indole and acid from sucrose and could be easily differentiated from other mannitol-negative species. All strains carried the aerA and lafA virulence genes and showed susceptibility to all antibiotics tested. Seafood could be a transmission route of this bacterium to humans. PMID- 26825090 TI - Neurobehavioral and Cognitive Changes Induced by Hypoxia in Healthy Volunteers. AB - The early assessment of new symptomatic drugs against Alzheimer's disease remains difficult because of the lack of a predictive end-point. The use of a battery including different parameters could improve this early development. In order to test the reverse effect of symptomatic drugs in healthy volunteers, scientists have developed new experimental paradigms to artificially induce transient cognitive impairments in healthy volunteers akin to those observed in Alzheimer's disease, i.e. Cognitive Challenge Models. In this context, transient hypoxia could be a relevant Cognitive Challenge Model. The deleterious effects of hypoxia on cognition, as described in the literature, should be considered carefully since they are usually assessed with different populations that do not have the same hypoxic sensitivity. Hypoxia can be obtained by the means of two different methods: normobaric and hypobaric hypoxia. In both designs, cognitive changes can be directly modulated by the severity of hypoxic levels. The purpose of this review is to gather existing support on the application of hypoxia within different cognitive domains and to highlight the scientific interests of such a model to predict and select promising drug candidates. We aimed at reviewing in detail the methods, designs and cognitive paradigms used in non-pharmacological hypoxia studies. Probing the four main cognitive functions will allow identifying the extent to which different hypoxia designs selectively compromise cognitive functioning. For each cognitive process, the convergent and divergent results are discussed in terms of paradigm differences whereas we will focus on defining the optimal methodology for obtaining the desired effects. PMID- 26825091 TI - The TT allele of rs405509 synergizes with APOE epsilon4 in the impairment of cognition and its underlying default mode network in non-demented elderly. AB - BACKGROUND: Evidence demonstrates that the T allele of the single-nucleotide polymorphism rs405509 as the apolipoprotein E (APOE) promoter is a risk factor for Alzheimer's disease (AD). However, it is unclear the APOE-rs405509 interaction effect on brain spontaneous activity. METHODS: We analyzed the interaction of the rs405509 TT allele and the APOE epsilon4 allele on cognitive performances measured using neuropsychological tests and brain default mode network (DMN) defined by independent component analysis using based on resting state functional magnetic resonance imaging data among the non-demented elderly people. RESULTS: Significant interaction was found between rs405509 and APOE on general mental status, memory and attention (p<0.05). Functional network analysis showed a significantly APOE-rs405509 interaction on anterior cingulate gyrus, medial frontal region and precuneus at anterior and posterior DMN (False Discovery Rate p<0.05). Additionally, significant correlations were found between cognitive performance and DMN connectivity (p<0.05). CONCLUSION: The data indicates that the APOE-rs405509 interaction impairs elderly's cognitive performance through brain functional network. PMID- 26825092 TI - Glial Cells - The Key Elements of Alzheimer's Disease. AB - Alzheimer's disease (AD) is a complex neurodegenerative disorder with major clinical hallmarks of memory loss, dementia, and cognitive impairment. Besides the extensive neuron-oriented research, an increasing body of evidence suggests that glial cells, namely astrocytes, microglia, NG2 glia and oligodendrocytes, may play an important role in the pathogenesis of this disease. In the first part of this review, AD pathophysiology in humans is briefly described and compared with disease progression in routinely used animal models. The relevance of findings obtained in animal models of AD is also discussed with respect to AD pathology in humans. Further, this review summarizes recent findings regarding the role/participation of glial cells in pathogenesis of AD, focusing on changes in their morphology, functions, proteins and gene expression profiles. As for astrocytes and microglia, they are fundamental for the progression and outcome of AD either because they function as effector cells releasing cytokines that play a role in neuroprotection, or because they fail to fulfill their homeostatic functions, ultimately leaving neurons to face excitotoxicity and oxidative stress. Next, we turn our attention towards NG2 glia, a novel and distinct class of glial cells in the central nervous system (CNS), whose role in a variety of human CNS diseases has begun to emerge, and we also consider the participation of oligodendrocytes in the pathogenesis and progression of AD. Since AD is currently an incurable disease, in the last part of our review we hypothesize about possible glia-oriented treatments and provide a perspective of possible future advancements in this field. PMID- 26825093 TI - Cerebrospinal Fluid proNGF: A Putative Biomarker for Early Alzheimer's Disease. AB - The discovery of biomarkers for the onset of Alzheimer's disease (AD) is essential for disease modification strategies. To date, AD biomarker studies have focused on brain imaging and cerebrospinal fluid (CSF) changes in amyloid- beta (Abeta) peptide and tau proteins. While reliable to an extent, this panel could be improved by the inclusion of novel biomarkers that optimize sensitivity and specificity. In this study, we determined whether CSF levels of the nerve growth factor (NGF) precursor protein, proNGF, increased during the progression of AD, mirroring its up regulation in postmortem brain samples of people who died with a clinical diagnosis of mild cognitive impairment (MCI) or AD. Immunoblot analysis was performed on ventricular CSF harvested from participants in the Rush Religious Orders Study with an antemortem clinical diagnosis of no cognitive impairment (NCI), amnestic MCI (aMCI, a putative prodromal AD stage), or mild/moderate AD. ProNGF levels were increased 55% in aMCI and 70% in AD compared to NCI. Increasing CSF proNGF levels correlated with impairment on cognitive test scores. In a complementary study, we found that proNGF was significantly increased by 30% in lumbar CSF samples derived from patients with a clinical dementia rating (CDR) of 0.5 or 1 compared to those with a CDR = 0. Notably, proNGF/Abeta1-42 levels were 50% higher in CDR 0.5 and CDR 1 compared to CDR 0 controls. By contrast, ELISA measurements of CSF brain-derived neurotrophic factor (BDNF) did not distinguish aMCI from NCI. Taken together, these results suggest that proNGF protein levels may augment the diagnostic accuracy of currently used CSF biomarker panels. PMID- 26825095 TI - Urinary Metabolomics Reveals Alterations of Aromatic Amino Acid Metabolism of Alzheimer's Disease in the Transgenic CRND8 Mice. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with amyloid plaques accumulation as the key feature involved in its pathology. To date, however, the biochemical changes in AD have not been clearly characterized. Here, we present that urinary metabolomics based on high resolution mass spectrometry was employed for delineation of metabolic alterations in transgenic CRND8 mice. In this noninvasive approach, urinary metabolome reveals the biochemical changes in early onset of this AD mouse model. In virtue of comprehensive metabolite profiling and multivariate statistical analysis, a total of 73 differential metabolites of urine sample sets was identified in 12-week and 18-week transgenic mice compared to wild-type littermates, covering perturbations of aromatic amino acid metabolism, the Krebs cycle and one-carbon metabolism. Of particular interest is that divergent tryptophan metabolism, such as upregulation of serotonin pathway while downregulation of kynurenine pathway, was observed. Meanwhile, the accumulation of both N-acetylvanilalanine and 3-methoxytyrosine indicated aromatic L-amino acid decarboxylase deficiency. And the microbial metabolites derived from aromatic amino acid metabolism and drug-like phase II metabolic response via the glycine conjugation reactions were also highlighted, indicating that genetic modification in mouse brain not only alters genotype but also perturbs the gut microbiome. Together, our study demonstrated that the integrative approach employing mass spectrometry-based metabolomics and a transgenic mouse model for AD may provide new evidence for distinct metabolic signatures. The perturbations of metabolic pathways may have far-reaching implications for early diagnosis and intervention in AD. PMID- 26825096 TI - Metabolomic-Driven Elucidation of Serum Disturbances Associated with Alzheimer's Disease and Mild Cognitive Impairment. AB - Numerous efforts have been made in the last years to discover potential biomarkers of Alzheimer's disease and its progression from mild cognitive impairment, considered as an intermediate phase in the development of Alzheimer's disease from normal aging. However, there is still a considerable lack of understanding about pathological mechanisms underlying to disease. In the present study, serum metabolomics based on ultra-high-performance liquid chromatographymass spectrometry was applied to investigate metabolic differences between subjects with Alzheimer's disease and mild cognitive impairment, as well as healthy controls. The most important findings can be associated with impaired metabolism of phospholipids and sphingolipids leading to membrane breakdown, wherein the nature of the fatty acids contained in the structure in terms of acyl chain length and degree of unsaturation appears to play a crucial role. Furthermore, several discriminant metabolites were found for the first time in relation to known pathological processes associated with Alzheimer's disease, such as the accumulation of acylcarnitines in relation to mitochondrial dysfunction, decreased levels of oleamide and monoglycerides as a result of defects in endocannabinoid system, or increased serum phenylacetylglutamine, which could reveal alterations in glutamine homeostasis. Therefore, these results represent a suitable approximation to understand the pathogenesis and progression of the disease. PMID- 26825094 TI - Increased Epileptiform EEG Activity and Decreased Seizure Threshold in Arctic APP Transgenic Mouse Model of Alzheimer's Disease. AB - Several Alzheimer model mice carrying transgenic amyloid precursor protein (APP) with the Swedish mutation have been reported to exhibit spontaneous seizures and/or increased epileptiform EEG activity. The primary cause for the epilepsy phenotype is still under debate. In contrast to mice with APPswe mutation that develop extracellular amyloid plaques, mice with APP Arctic mutation (E693G) have no bias toward beta-secretase cleavage and display intracellular amyloid deposits but not plaques. We conducted a systematic long-term video-EEG recording in three two-week sessions on 21 APParc and 11 wild-type control mice between 3.5 and 8 months of age. Spontaneous seizures were not detected more often in APParc mice than in their wild-type control mice. Long (1 - 5 s) epileptiform discharges were occasionally detected in both APParc and wild-type mice, but short (0.5 - <1 s) epileptiform discharges were more common in APParc mice than in wild-types. However, they were far less frequent than in 6 APPswe/PS1dE9 mice recorded in parallel. In pentylenetetrazole test for seizure susceptibility, APParc mice displayed a shorter latency to sharp-wave discharges than wildtype mice but no increase in seizure duration. These data speak for a relatively mild epilepsy phenotype in APParc mice compared to APPswe mice despite even higher extent of APP overexpression. Thus extracellular amyloid plaques or increased beta secretase cleavage products appear important for the epilepsy phenotype in APPswe mice. PMID- 26825097 TI - Probabilistic Cost-Effectiveness Analysis of Vaccination for Mild or Moderate Alzheimer's Disease. AB - BACKGROUND: Studies on the immunotherapy for Alzheimer's disease (AD) have increasingly gained attention since 1990s. However, there are pros (preventing of AD) and cons (incurred cost and side effects) regarding the administration of immunotherapy. Up to date, there has been lacking of economic evaluation for immunotherapy of AD. We aimed to assess the cost-effectiveness analysis of the vaccination for AD. METHODS: A meta-analysis of randomized control trials after systemic review was conducted to evaluate the efficacy of the vaccine. A Markov decision model was constructed and applied to a 120,000-Taiwanese cohort aged >=65 years. Person years and quality-adjusted life years (QALY) were computed between the vaccinated group and the the unvaccinated group. Economic evaluation was performed to calculate the incremental cost-effectiveness ratio (ICER) and cost-effectiveness acceptability curve (CEAC). RESULTS: Vaccinated group gained an additional 0.84 life years and 0.56 QALYs over 10-years and an additional 0.35 life years and 0.282 QALYs over 5-years of follow-up. The vaccinated group dominated the unvaccinated group by ICER over 5-years of follow-up. The ICERs of 10-year follow-up for the vaccinated group against the unvaccinated group were $13,850 per QALY and $9,038 per life year gained. Given the threshold of $20,000 of willingness to pay (WTP), the CEAC showed the probability of being cost effective for vaccination with QALY was 70.7% and 92% for life years gained after 10-years of follow-up. The corresponding figures were 87.3% for QALY and 93.5% for life years gained over 5-years follow-up. CONCLUSION: The vaccination for AD was cost-effective in gaining QALY and life years compared with no vaccination, under the condition of a reasonable threshold of WTP. PMID- 26825098 TI - American Society of Nephrology Quiz and Questionnaire 2015: Electrolytes and Acid Base Disorders. AB - The Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the annual Kidney Week meeting of the American Society of Nephrology. During the 2015 meeting the conference hall was once again overflowing with eager quiz participants. Topics covered by the experts included electrolyte and acid-base disorders, glomerular disease, end-stage renal disease and dialysis, and kidney transplantation. Complex cases representing each of these categories together with single-best-answer questions were prepared and submitted by the panel of experts. Before the meeting, training program directors of nephrology fellowship programs and nephrology fellows in the United States answered the questions through an internet-based questionnaire. During the live session members of the audience tested their knowledge and judgment on the same series of case-oriented questions in a quiz. The audience compared their answers in real time using a cell-phone app containing the answers of the nephrology fellows and training program directors. The results of the online questionnaire were displayed, and then the quiz answers were discussed. As always, the audience, lecturers, and moderators enjoyed this highly educational session. This article recapitulates the session and reproduces selected content of educational value for theClinical Journal of the American Society of Nephrologyreaders. Enjoy the clinical cases and expert discussions. PMID- 26825099 TI - Augmented trial designs for evaluation of principal surrogates. AB - Observation of counterfactual intermediate responses, and evaluation of them as candidate surrogates, is complicated in a standard randomized trial as half of the responses are systematically missing by design. Although some augmentation procedures exist for obtaining counterfactual responses, they are specific to vaccine trials. We outline extensions to the existing augmentations and suggest augmentations of three trial designs outside the setting of vaccines. We outline the assumptions needed to identify the causal estimands of interest under each augmented design, under which standard likelihood-based methods can be used to evaluate intermediate responses as principal surrogates. Two of these designs, crossover and individual stepped-wedge, allow for the observation of clinical endpoints under both treatment and control for some subset of subjects and can therefore improve efficiency over standard parallel trial designs. The third, the treatment run-in design, allows for the observation of a baseline measure that may be as useful a surrogate as the true counterfactual intermediate response. As the evaluation methods rely on several assumptions, we also outline a remediation analysis, which can be used to help overcome assumption violations. We illustrate our suggested methods in an example from a drug-resistant tuberculosis treatment trial. PMID- 26825100 TI - Health Care Austerity Measures in Times of Crisis: The Perspectives of Primary Health Care Physicians in Madrid, Spain. AB - The current financial crisis has seen severe austerity measures imposed on the Spanish health care system, including reduced public spending, copayments, salary reductions, and reduced services for undocumented migrants. However, the impacts have not been well-documented. We present findings from a qualitative study that explores the perceptions of primary health care physicians in Madrid, Spain. This article discusses the effects of austerity measures implemented in the public health care system and their potential impacts on access and utilization of primary health care services. This is the first study, to our knowledge, exploring the health care experiences during the financial crisis of general practitioners in Madrid, Spain. The majority of participating physicians disapproved of austerity measures implemented in Spain. The findings of this study suggest that undocumented migrants should regain access to health care services; copayments should be minimized and removed for patients with low incomes; and health care professionals should receive additional help to avoid burnout. Failure to implement these measures could result in the quality of health care further deteriorating and could potentially have long-term negative consequences on population health. PMID- 26825101 TI - Swim performance and thermoregulatory effects of wearing clothing in a simulated cold-water survival situation. AB - PURPOSE: Accidental cold-water immersion (CWI) impairs swim performance, increases drowning risk and often occurs whilst clothed. The impact of clothing on thermoregulation and swim performance during CWI was explored with the view of making recommendations on whether swimming is viable for self-rescue; contrary to the traditional recommendations. METHOD: Ten unhabituated males (age 24 (4) years; height 1.80 (0.08) m; mass 78.50 (10.93) kg; body composition 14.8 (3.4) fat %) completed four separate CWIs in 12 degrees C water. They either rested clothed or naked (i.e. wearing a bathing costume) or swum self-paced clothed or naked for up to 1 h. Swim speed, distance covered, oxygen consumption and thermal responses (rectal temperature (T re), mean skin temperature (T msk) and mean body temperature T b) were measured. RESULTS: When clothed, participants swum at a slower pace and for a significantly shorter distance (815 (482) m, 39 (19) min) compared to when naked (1264 (564) m, 52 (18) min), but had a similar oxygen consumption indicating clothing made them less efficient. Swimming accelerated the rate of T msk and T b cooling and wearing clothing partially attenuated this drop. The impairment to swimming performance caused by clothing was greater than the thermal benefit it provided; participants withdrew due to exhaustion before hypothermia developed. CONCLUSION: Swimming is a viable self-rescue method in 12 degrees C water, however, clothing impairs swimming capability. Self-rescue swimming could be considered before clinical hypothermia sets in for the majority of individuals. These suggestions must be tested for the wider population. PMID- 26825103 TI - An Ethical Framework for Allocating Scarce Life-Saving Chemotherapy and Supportive Care Drugs for Childhood Cancer. AB - Shortages of life-saving chemotherapy and supportive care agents for children with cancer are frequent. These shortages directly affect patients' lives, compromise both standard of care therapies and clinical research, and create substantial ethical challenges. Efforts to prevent drug shortages have yet to gain traction, and existing prioritization frameworks lack concrete guidance clinicians need when faced with difficult prioritization decisions among equally deserving children with cancer. The ethical framework proposed in this Commentary is based upon multidisciplinary expert opinion, further strengthened by an independent panel of peer consultants. The two-step allocation process includes strategies to mitigate existing shortages by minimizing waste and addresses actual prioritization across and within diseases according to a modified utilitarian model that maximizes total benefit while respecting limited constraints on differential treatment of individuals. The framework provides reasoning for explicit decision-making in the face of an actual drug shortage. Moreover, it minimizes bias that might occur when individual clinicians or institutions are forced to make bedside rationing and prioritization decisions and addresses the challenge that individual clinicians face when confronted with bedside decisions regarding allocation. Whenever possible, allocation decisions should be supported by evidence-based recommendations. "Curability," prognosis, and the incremental importance of a particular drug to a given patient's outcome are the critical factors to consider when deciding how to allocate scarce life saving cancer drugs. PMID- 26825104 TI - Coordinate older age care around people, not services, says report. PMID- 26825105 TI - Discouraged by Peer Excellence: Exposure to Exemplary Peer Performance Causes Quitting. AB - People are exposed to exemplary peer performances often (and sometimes by design in interventions). In two studies, we showed that exposure to exemplary peer performances can undermine motivation and success by causing people to perceive that they cannot attain their peers' high levels of performance. It also causes de-identification with the relevant domain. We examined such discouragement by peer excellence by exploiting the incidental exposure to peers' abilities that occurs when students are asked to assess each other's work. Study 1 was a natural experiment in a massive open online course that employed peer assessment (N = 5,740). Exposure to exemplary peer performances caused a large proportion of students to quit the course. Study 2 explored underlying psychological mechanisms in an online replication (N = 361). Discouragement by peer excellence has theoretical implications for work on social judgment, social comparison, and reference bias and has practical implications for interventions that induce social comparisons. PMID- 26825102 TI - Exploiting IL-17-producing CD4+ and CD8+ T cells to improve cancer immunotherapy in the clinic. AB - Cancer immunotherapy is one the most effective approaches for treating patients with tumors, as it bolsters the generation and persistence of memory T cells. In preclinical work, it has been reported that adoptively transferred CD4+ and CD8+ lymphocytes that secrete IL-17A (i.e., Th17 and Tc17 cells) regress tumors to a greater extent than IFN-gamma(+)Th1 or Tc1 cells in vivo. Herein, we review the mechanisms underlying how infused Th17 and Tc17 cells regress established malignancies in clinically relevant mouse models of cancer. We also discuss how unique signaling cues--such as co-stimulatory molecules (ICOS and 41BB), cytokines (IL-12 and IL-23) or pharmaceutical reagents (Akt inhibitors, etc.)- can be exploited to bolster the therapeutic potential of IL-17(+) lymphocytes with an emphasis on using this knowledge to improve next-generation clinical trials for patients with cancer. PMID- 26825106 TI - Pleasure Now, Pain Later: Positive Fantasies About the Future Predict Symptoms of Depression. AB - Though common sense suggests that positive thinking shelters people from depression, the four studies reported here showed that this intuition needs to be qualified: Positive thinking in the form of fantasies about the future did indeed relate to decreased symptoms of depression when measured concurrently; however, positive fantasies predicted more depressive symptoms when measured longitudinally. The pattern of results was observed for different indicators of fantasies and depression, in adults and in schoolchildren, and for periods of up to 7 months (Studies 1-4). In college students, low academic success partially mediated the predictive relation between positive fantasies and symptoms of depression (Study 4). Results add to existing research on the problematic effects of positive fantasies on performance by suggesting that indulging in positive fantasies predicts problems in mental health. PMID- 26825107 TI - Clinical and angiographic outcomes associated with surgical revascularization of angiographically borderline 50-69% coronary artery stenoses. AB - OBJECTIVES: Coronary artery bypass grafting (CABG) improves outcomes in patients with multivessel coronary artery disease. Bypass of angiographically significant lesions >=70% is recommended, yet little is known about the incidence/outcomes with bypasses of 50-69% angiographically borderline lesions (ABLs) without fractional flow reserve testing. The objective of this study was to investigate the incidence and outcomes of bypass of 50-69% ABLs. METHODS: Between 2007 and 2013, 3195 patients underwent isolated first multivessel CABG. Patients with an isolated ABL of a major epicardial vessel were included. Outcomes of interest included time to all-cause mortality, and 30-day and 1-year mortality. RESULTS: Among 350 patients with an ABL, 268 (76.6%) had the vessel containing the ABL bypassed, while 82 (23.4%) did not. The mean follow-up was 4.2 years. Patients with a bypassed ABL were older (66.1 vs 62.5 mean years, P = 0.006) but otherwise similar in sex, comorbidities, diabetes, ejection fraction and number of coronary stenoses. Cardiopulmonary bypass time was longer in patients with bypassed ABLs (104.2 vs 90.4 min, mean, P < 0.001). Unadjusted overall mortality until the end of follow-up was higher among patients with bypassed ABLs (11.6 vs 3.7%, P = 0.034). After multivariable adjustment, the association between ABL bypass and mortality was attenuated (hazard ratio 2.84, 95% confidence interval: 0.87-9.23, P = 0.080). No differences were observed in unadjusted 30-day (1.1 vs 0.0%, P = 0.336) or 1-year mortality (4.1 vs 0.0%, P = 0.062). Repeat revascularization rate of patients with bypassed ABLs was numerically higher (4.1 vs 0.0%, P = 0.107). CONCLUSIONS: In an unselected cohort of patients with ABLs, bypass of borderline 50-69% lesions is frequently performed and not associated with improved long-term survival. Our findings suggest that the routine surgical revascularization of 50-69% ABLs may not be warranted. PMID- 26825108 TI - The association between body mass index and outcome after coronary artery bypass grafting operations. AB - OBJECTIVES: This investigation was undertaken to analyse the association between body mass index (BMI) and morbidity after coronary artery bypass graft (CABG) operations. METHODS: The setting was a cardiovascular intensive care unit (ICU) of a tertiary medical referral centre. This was a retrospective review; patients were classified according to their BMI into five groups: underweight <18.5 kg/m(2); normal weight 18.5-24.9 kg/m(2); overweight 25-29.9 kg/m(2); Class I obesity 3034.9 kg/m(2); and Class II/III obesity >35 kg/m(2). We included patients who underwent isolated CABG between January 3, 2006 and March 8, 2011. After including only the initial operation or admission in patients with more than one operation or hospital admission and excluding patients with any missing variable, 3470 patients remained in the analyses. The primary outcomes analysed were hospital mortality and pulmonary and infection morbidities. We secondarily assessed the association between BMI category and each of the three outcomes. RESULTS: Respective mortality, and pulmonary and infection morbidity occurrence rates were: 8.7, 13.0 and 13.0% for the underweight; 2.4, 8.0 and 4.8% for the overweight; 1.8, 10.9 and 5.6% for the Class I obesity group; and 2.7, 11.1 and 5.7% for the Class II/III obesity group, vs 2.3, 7.0 and 6.2% for the normal weight group. Class I and II/III obesity patients were more likely to have pulmonary morbidity compared with the normal weight group, after adjusting for the potential confounding variables. CONCLUSIONS: Class I and Class II/III obesity (BMI >=30 kg/m(2)) was associated with increased pulmonary morbidity after CABG operations. There was no difference in mortality or infection morbidity in any BMI group compared with the normal group. PMID- 26825109 TI - Effectiveness of balance training programme in reducing the frequency of falling in established osteoporotic women: a randomized controlled trial. AB - OBJECTIVE: To investigate the effect of a 12-month sensomotor balance exercise programme on postural control and the frequency of falling in women with established osteoporosis. DESIGN: Randomized controlled trial where the intervention group was assigned the 12-month Balance Training Programme and the control group did not undertake any intervention beyond regular osteoporosis treatment. SUBJECTS: A total of 100 osteoporotic women - at least with one osteoporotic fracture - aged 65 years old and above. MAIN MEASURES: Balance was assessed in static and dynamic posture both with performance-based measures of balance, such as the Berg Balance Scale and the Timed Up and Go Test, and with a stabilometric computerized platform. INTERVENTIONS: Patients in the intervention group completed the 12-month sensomotor Balance Training Programme in an outpatient setting, guided by physical therapists, three times a week, for 30 minutes. RESULTS: The Berg Balance Scale and the Timed Up and Go Test showed a statistically significant improvement of balance in the intervention group ( p = 0.001 and p = 0.005, respectively). Balance tests using the stabilometer also showed a statistically significant improvement in static and dynamic postural balance for osteoporotic women after the completion of the Balance Training Programme. As a consequence, the one-year exercise programme significantly decreased the number of falls in the exercise group compared with the control group. CONCLUSION: The Balance Training Programme significantly improved the balance parameters and reduced the number of falls in postmenopausal women who have already had at least one fracture in the past. PMID- 26825110 TI - Development and validation of parallel short forms PaSA-cardio for the assessment of general anxiety in cardiovascular rehabilitation patients using Rasch analysis. AB - OBJECTIVE: To develop and validate parallel short forms for the assessment of general anxiety in cardiovascular rehabilitation patients, that facilitate repeated measurement over time without contamination from residual practice effect variance. DESIGN: Development of the parallel short forms using Rasch analysis. Validation study. SETTING: Cardiac rehabilitation centres in Germany. SUBJECTS: Cardiovascular rehabilitation patients. INTERVENTIONS: Not applicable. MAIN MEASURES: Parallel short forms PaSA-cardio, Hospital Anxiety and Depression Scale, Short Form Health Survey SF-12 and Structured Clinical Interview for DSM IV Axis I Disorders. RESULTS: Each version of the parallel short forms (PaSA cardio-I and PaSA-cardio-II) comprises ten items. The two forms fitted to the Rasch model with a non-significant item-trait interaction (PaSA-cardio-I: chi square = 39.49, degrees of freedom = 30, probability = 0.12; PaSA-cardio-II: chi square = 26.56, degrees of freedom = 30, probability = 0.65). Person-separation reliability was 0.75/0.76. Unidimensionality could be verified. Correlation between the two models was 0.94 and 0.95, and correlations with the underlying item bank were 0.95 and 0.93. Validity could be confirmed. The area under the curve was between 0.88 and 0.97 for PaSA-cardio-I and between 0.92 and 0.95 for PaSA-cardio-II. CONCLUSIONS: Assessment of general anxiety in cardiovascular rehabilitation patients with the PaSA-cardio was valid, economical and accurate. The two forms of the PaSA-cardio are equivalent and allow retest without contamination from residual practice effect variance. PMID- 26825112 TI - QnAs with Daniel Neumark. PMID- 26825111 TI - Increasing Access to Mental Health Care With Breathe, an Internet-Based Program for Anxious Adolescents: Study Protocol for a Pilot Randomized Controlled Trial. AB - BACKGROUND: There is a demand to make first-line treatments, including cognitive behavioural therapy (CBT) for adolescent anxiety disorders, more widely available. Internet-based CBT is proposed to circumvent access and availability barriers and reduce health care system costs. Recent reviews suggest more evidence is needed to establish the treatment effects of Internet-based CBT in children and adolescents and to determine related economic impacts. OBJECTIVE: This pilot trial aims to collect the necessary data to inform the planning of a full-scale RCT to test the effectiveness of the Internet-based CBT program Breathe (Being Real, Easing Anxiety: Tools Helping Electronically). METHODS: We are conducting a 27-month, 2-arm parallel-group, pilot randomized controlled trial (RCT). Outcomes will inform the planning of a full-scale RCT aimed to test the effectiveness of Internet-based CBT with a population of adolescents with moderate to mild anxiety problems. In the pilot RCT we will: (1) define a minimal clinically important difference (MCID) for the primary outcome measure (total anxiety score using the Multidimensional Anxiety Scale for Children); (2) determine a sample size for the full-scale RCT; (3) estimate recruitment and retention rates; (4) measure intervention acceptability to inform critical intervention changes; (5) determine the use of co-interventions; and (6) conduct a cost-consequence analysis to inform a cost-effectiveness analysis in the full scale RCT. Adolescents aged 13-17 years seeking care for an anxiety complaint from a participating emergency department, mobile or school-based crisis team, or primary care clinic are being screened for interest and eligibility. Enrolled adolescents are being randomly allocated to either 8 weeks of Internet-based CBT with limited telephone and e-mail support, or a control group with access to a static webpage listing anxiety resources. Adolescents are randomly assigned using a computer generated allocation sequence. Data are being collected at baseline, treatment completion, and at a 3-month follow-up. RESULTS: Currently, adolescents are being enrolled in the study. Enrolment is taking place between March 2014 and February 2016; data collection will conclude May 2016. We expect that analysis and results will be available by August 2016. CONCLUSIONS: In many communities, the resources available for front-line anxiety treatment are outweighed by the need for care. This pilot RCT is an essential step to designing a robust RCT to evaluate the effectiveness of an Internet-based CBT program for adolescents with moderate to mild anxiety problems. TRIAL REGISTRATION: Clinicaltrials.gov NCT02059226; http://clinicaltrials.gov/ct2/show/NCT02059226 (Archived by WebCite at http://www.webcitation.org/6epF8v7k4). PMID- 26825113 TI - Expanding the phenotype half of the genotype-phenotype space. PMID- 26825114 TI - Monolithically integrated broad-band Mach-Zehnder interferometers for highly sensitive label-free detection of biomolecules through dual polarization optics. AB - Protein detection and characterization based on Broad-band Mach-Zehnder Interferometry is analytically outlined and demonstrated through a monolithic silicon microphotonic transducer. Arrays of silicon light emitting diodes and monomodal silicon nitride waveguides forming Mach-Zehnder interferometers were integrated on a silicon chip. Broad-band light enters the interferometers and exits sinusoidally modulated with two distinct spectral frequencies characteristic of the two polarizations. Deconvolution in the Fourier transform domain makes possible the separation of the two polarizations and the simultaneous monitoring of the TE and the TM signals. The dual polarization analysis over a broad spectral band makes possible the refractive index calculation of the binding adlayers as well as the distinction of effective medium changes into cover medium or adlayer ones. At the same time, multi-analyte detection at concentrations in the pM range is demonstrated. PMID- 26825115 TI - The Experience of Mothers Exposed to the Abuse of Their Daughters by an Intimate Partner: "There Is No Definition for It". AB - This qualitative study illuminates the experience of mothers exposed to the intimate partner violence (IPV) of their daughters. In-depth interviews with 11 exposed mothers were conducted. The findings reveal four semi-chronological phases in the participants' experiences: pre-disclosure of the daughter's abuse, the first definitive encounter with the daughter's abuse, living with continued exposure to the daughter's IPV, and the aftermath of the daughter's IPV. A recurrent theme in the mothers' experiences was their dual positioning as a forgotten victim of IPV and as a caregiver of their daughter shaped by prevalent motherhood ideologies. Possible implications for intervention are discussed. PMID- 26825116 TI - Breaking the Silence at Spanish Universities: Findings From the First Study of Violence Against Women on Campuses in Spain. AB - The first research conducted on violence against women in the university context in Spain reveals that 62% of the students know of or have experienced situations of this kind within the university institutions, but only 13% identify these situations in the first place. Two main interrelated aspects arise from the data analysis: not identifying and acknowledging violent situations, and the lack of reporting them. Policies and actions developed by Spanish universities need to be grounded in two goals: intransigence toward any kind of violence against women, and bystander intervention, support, and solidarity with the victims and with the people supporting the victims. PMID- 26825117 TI - Depression in Women Who Have Left Violent Relationships: The Unique Impact of Frequent Emotional Abuse. AB - Intimate partner violence (IPV) exposure has been associated with poor mental health outcomes for victims, but fewer studies have examined the unique contributions of emotional abuse to mental health. This study explored the contextual relationships between the type and frequency of IPV, community factors, and emotional health. Data were collected from a community-based IPV intervention program. Logistic regression found an increased likelihood of depression for respondents who experienced emotional abuse more than once per week (odds ratio [OR] = 4.864) and were worried about contact by the abuser (OR = 5.898). Results indicate the need for specific policy and practice attention to this issue. PMID- 26825118 TI - Bactericidal effects of polyhexamethylene biguanide against intracellular Staphylococcus aureus EMRSA-15 and USA 300. AB - OBJECTIVES: The treatment of skin infections caused by Staphylococcus aureus is limited by acquired antibiotic resistance and poor drug delivery into pathogen and host cells. Here, we investigated the antibacterial activities of six topically used antimicrobials and a cationic polymer, polyhexamethylene biguanide (PHMB), against intracellular MSSA strain RN4420 and MRSA strains EMRSA-15 and USA 300. METHODS: The MICs of antimicrobials were determined for MSSA and MRSA strains, and the bactericidal activities of nadifloxacin and PHMB against intracellular MRSA were determined using infected keratinocytes. Fluorescein tagged PHMB (PHMB-FITC) was used to study PHMB uptake, co-localization with intracellular EMRSA-15 and retention in keratinocytes. The mechanism(s) of PHMB uptake into keratinocytes were studied using a dynamin inhibitor, dynasore. RESULTS: Gentamicin, nadifloxacin and PHMB showed the lowest MICs for MRSA. Nadifloxacin at 10 mg/L killed 80% of intracellular EMRSA-15, but was not effective against USA 300. PHMB at 4 mg/L killed almost 100% of intracellular EMRSA-15 and USA 300. PHMB entered keratinocytes, co-localized with intracellular EMRSA-15 and was retained by the cells for over 5 h. PHMB uptake and its intracellular antibacterial activities were inhibited by the dynamin inhibitor, dynasore. CONCLUSIONS: PHMB kills intracellular MRSA via direct interaction with pathogens inside keratinocytes and host cell entry is dynamin dependent. PMID- 26825120 TI - Evaluation of two new commercial immunochromatographic assays for the rapid detection of OXA-48 and KPC carbapenemases from cultured bacteria. AB - BACKGROUND: Rapid detection and confirmation of carbapenemases remains very challenging for diagnostic laboratories. OBJECTIVES: The objective of this study was to assess the performance of two new immunochromatographic (IC) commercial assays for the rapid detection of OXA-48-producing and KPC-producing Enterobacteriaceae in pure bacterial isolates. METHODS: A panel of 92 bacterial isolates predominantly including carbapenem-non-susceptible Enterobacteriaceae with previously defined carbapenem resistance mechanisms was tested. Then, 342 consecutive carbapenem-non-susceptible Enterobacteriaceae isolates referred to the reference laboratory were investigated prospectively in parallel with other phenotypic tests and with multiplex PCR and sequencing as the gold standard. RESULTS: In the collection panel, each of the two IC assays correctly detected all 30 OXA-48-like-producing isolates and 25 KPC-producing isolates, whatever the species, their association with other beta-lactamases and the level of resistance to carbapenems. All other carbapenemase producers and all non-carbapenemase producing isolates yielded negative results with both tests. In the prospective evaluation, all OXA-48-like-producing Enterobacteriaceae isolates (n = 130) and KPC-producing Enterobacteriaceae isolates (n = 33) were correctly detected by the individual IC assays, while 179 non-OXA-48-like-producing and non-KPC-producing strains (137 non-carbapenemase producers and 42 isolates belonging to other carbapenemase family types) yielded negative results. Thus, each assay yielded 100% sensitivity and 100% specificity for the detection of OXA-48-like or KPC enzymes, respectively, at 15 min. CONCLUSIONS: The two IC assays allow rapid and reliable direct confirmation of OXA-48 and KPC carbapenemases from culture colonies and appear to be very useful additions to the existing tests, obviating the need for more costly characterization by molecular amplification methods. PMID- 26825121 TI - Small Rho GTPase-mediated actin dynamics at endothelial adherens junctions. AB - VE-cadherin-based cell-cell junctions form the major restrictive barrier of the endothelium to plasma proteins and blood cells. The function of VE-cadherin and the actin cytoskeleton are intimately linked. Vascular permeability factors and adherent leukocytes signal through small Rho GTPases to tightly regulate actin cytoskeletal rearrangements in order to open and re-assemble endothelial cell cell junctions in a rapid and controlled manner. The Rho GTPases are activated by guanine nucleotide exchange factors (GEFs), conferring specificity and context dependent control of cell-cell junctions. Although the molecular mechanisms that couple cadherins to actin filaments are beginning to be elucidated, specific stimulus-dependent regulation of the actin cytoskeleton at VE-cadherin-based junctions remains unexplained. Accumulating evidence has suggested that depending on the vascular permeability factor and on the subcellular localization of GEFs, cell-cell junction dynamics and organization are differentially regulated by one specific Rho GTPase. In this Commentary, we focus on new insights how the junctional actin cytoskeleton is specifically and locally regulated by Rho GTPases and GEFs in the endothelium. PMID- 26825119 TI - Improved darunavir genotypic mutation score predicting treatment response for patients infected with HIV-1 subtype B and non-subtype B receiving a salvage regimen. AB - OBJECTIVES: The objective of this study was to improve the prediction of the impact of HIV-1 protease mutations in different viral subtypes on virological response to darunavir. METHODS: Darunavir-containing treatment change episodes (TCEs) in patients previously failing PIs were selected from large European databases. HIV-1 subtype B-infected patients were used as the derivation dataset and HIV-1 non-B-infected patients were used as the validation dataset. The adjusted association of each mutation with week 8 HIV RNA change from baseline was analysed by linear regression. A prediction model was derived based on best subset least squares estimation with mutational weights corresponding to regression coefficients. Virological outcome prediction accuracy was compared with that from existing genotypic resistance interpretation systems (GISs) (ANRS 2013, Rega 9.1.0 and HIVdb 7.0). RESULTS: TCEs were selected from 681 subtype B infected and 199 non-B-infected adults. Accompanying drugs were NRTIs in 87%, NNRTIs in 27% and raltegravir or maraviroc or enfuvirtide in 53%. The prediction model included weighted protease mutations, HIV RNA, CD4 and activity of accompanying drugs. The model's association with week 8 HIV RNA change in the subtype B (derivation) set was R(2) = 0.47 [average squared error (ASE) = 0.67, P < 10(-6)]; in the non-B (validation) set, ASE was 0.91. Accuracy investigated by means of area under the receiver operating characteristic curves with a binary response (above the threshold value of HIV RNA reduction) showed that our final model outperformed models with existing interpretation systems in both training and validation sets. CONCLUSIONS: A model with a new darunavir-weighted mutation score outperformed existing GISs in both B and non-B subtypes in predicting virological response to darunavir. PMID- 26825123 TI - Muscle RANK is a key regulator of Ca2+ storage, SERCA activity, and function of fast-twitch skeletal muscles. AB - Receptor-activator of nuclear factor-kappaB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscles preventing the loss of maximum specific force while promoting muscle atrophy, fatigability, and increased proportion of fast-twitch fibers. In denervated EDL muscles, RANK deletion markedly increased stromal interaction molecule 1 content, a Ca(2+)sensor, and altered activity of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) modulating Ca(2+)storage. Muscle RANK deletion had no significant effects on the sham or denervated slow twitch soleus muscles. These data identify a novel role for RANK as a key regulator of Ca(2+)storage and SERCA activity, ultimately affecting denervated skeletal muscle function. PMID- 26825124 TI - Pivotal role of AKAP121 in mitochondrial physiology. AB - In this Perspective, we discuss some recent developments in the study of the mitochondrial scaffolding protein AKAP121 (also known as AKAP1, or AKAP149 as the human homolog), with an emphasis on its role in mitochondrial physiology. AKAP121 has been identified to function as a key regulatory molecule in several mitochondrial events including oxidative phosphorylation, the control of membrane potential, fission-induced apoptosis, maintenance of mitochondrial Ca(2+)homeostasis, and the phosphorylation of various mitochondrial respiratory chain substrate molecules. Furthermore, we discuss the role of hypoxia in prompting cellular stress and damage, which has been demonstrated to mediate the proteosomal degradation of AKAP121, leading to an increase in reactive oxgyen species production, mitochondrial dysfunction, and ultimately cell death. PMID- 26825125 TI - Leaky ryanodine receptors delay the activation of store overload-induced Ca2+ release, a mechanism underlying malignant hyperthermia-like events in dystrophic muscle. AB - The mouse model of Duchenne muscular dystrophy, the mdx mouse, displays changes in Ca(2+)homeostasis that may lead to the pathology of the muscle. Here we examine the activation of store overload-induced Ca(2+)release (SOICR) in mdx muscle. The activation of SOICR is associated with the depolymerization of the sarcoplasmic reticulum (SR) Ca(2+)buffer calsequestrin and the reduction of SR Ca(2+)buffering power (BSR). The role of SOICR in healthy and dystrophic muscle is unclear. Using skinned fibers we show that lowering the Mg(2+)concentration can activate discrete Ca(2+)release events that did not necessarily lead to activation of SOICR. However, SOICR waves could propagate into these fiber segments. The average delay to activation of SOICR in mdx fibers was longer than in wild-type (WT) fibers. In the lowered Ca(2+)-buffered environment following large SOICR events, brief waves in mdx fibers displayed a low amplitude and propagation rate, in contrast to WT fibers that showed a range of amplitudes correlated with wave propagation rate. The distinct properties of SOICR in mdx fibers were consistent with a ryanodine receptor (RyR) that was leakier to Ca(2+)than in WT. The consequence of delayed SOICR and leaky RyRs is prolonged high BSRand a reduction in free Ca(2+)concentration inside the SR as total SR calcium drops. We present a hypothesis that SOICR activation is required in healthy muscle and that this mechanism works suboptimally in mdx fibers to fail to limit the activation of store-operated Ca(2+)entry. PMID- 26825122 TI - Molecular mechanisms of STIM/Orai communication. AB - Ca(2+)entry into the cell via store-operated Ca(2+)release-activated Ca(2+)(CRAC) channels triggers diverse signaling cascades that affect cellular processes like cell growth, gene regulation, secretion, and cell death. These store-operated Ca(2+)channels open after depletion of intracellular Ca(2+)stores, and their main features are fully reconstituted by the two molecular key players: the stromal interaction molecule (STIM) and Orai. STIM represents an endoplasmic reticulum located Ca(2+)sensor, while Orai forms a highly Ca(2+)-selective ion channel in the plasma membrane. Functional as well as mutagenesis studies together with structural insights about STIM and Orai proteins provide a molecular picture of the interplay of these two key players in the CRAC signaling cascade. This review focuses on the main experimental advances in the understanding of the STIM1-Orai choreography, thereby establishing a portrait of key mechanistic steps in the CRAC channel signaling cascade. The focus is on the activation of the STIM proteins, the subsequent coupling of STIM1 to Orai1, and the consequent structural rearrangements that gate the Orai channels into the open state to allow Ca(2+)permeation into the cell. PMID- 26825127 TI - Multiple Evaluations of Grant Proposals by Independent Assessors: Confirmatory Factor Analysis Evaluations of Reliability, Validity, and Structure. AB - External assessor ratings of the quality of the research team and of the proposed research were evaluated for proposals submitted to the highly competitive Australian Research Council large grants program. The structure of the responses by multiple assessors was evaluated using a series of nested models that are variations of the traditional congeneric, tau-equivalent, and parallel measurement models. The estimated reliability based on four independent assessors was modest but comparable to other peer review research: .494 for proposal ratings, .634 for researcher ratings, and .704 for a total assessment. Mean ratings (averaged over multiple assessors) of the proposal and the research team were highly correlated (r = .85), suggesting a lack of differentiation and a substantial method/halo effect in ratings by the same assessor. Confirmatory factor analysis models supported this suggestion, representing this method effect as correlated uniquenesses. Tests of whether proposal and researcher ratings reflected one or two latent variables, based on the internal structure of the assessment ratings and relations with external criteria (academic rank, prior funding, and publications), supported a one-factor solution. PMID- 26825126 TI - Danish Rural Eye Study: Epidemiology of Adult Visual Impairment. AB - PURPOSE: To examine the frequency and causes of visual impairment (VI) in a select population of Danish adults. METHODS: A total of 3843 adults aged 20-94 years from the Danish General Suburban Population Study (GESUS) were included in the population-based, cross-sectional ophthalmological study, Danish Rural Eye Study (DRES). All DRES participants received a comprehensive general health examination preceding their eye examination, including measurement of best corrected visual acuity (BCVA) for each eye, bilateral 45 degrees retinal fundus photographs and further ophthalmological examination where indicated. RESULTS: Overall, 3826 of 3843 participants (99.6%) had bilateral visual acuity measurements. The overall frequency of VI (BCVA <20/40 in the better-seeing eye) was 0.4% (95% confidence interval, CI, 0.2-0.7%; n = 15) among all DRES participants, 0.6% (95% CI 0.3-1.0%; n = 15) among participants >50 years and 3.7% (95% CI 2.1-6.5%; n = 11) in participants >80 years. The primary causes of VI in the better-seeing eye were age-related macular degeneration (AMD) in 46.7% (7/15) and cataract in 26.7% (4/15). A total of 43.3% (n = 115) of participants >80 years were pseudophakic in one or both eyes. The frequency of diabetes (HbA1c >= 48 mmol/mol or self-reported diagnosis) was 5.9% (n = 227), including 1.3% (n = 51) newly diagnosed in the GESUS. Of participants determined to have VI due to exudative AMD, 50% had received anti-vascular endothelial growth factor (VEGF) treatment. CONCLUSION: We report a relatively low frequency of VI among Danish adults over 59 years of age compared with that observed 10-15 years ago, which is both consistent with other recent Scandinavian studies and reflective of our relatively healthy and mobile population sample. PMID- 26825128 TI - Theoretic Fit and Empirical Fit: The Performance of Maximum Likelihood versus Generalized Least Squares Estimation in Structural Equation Models. AB - In research the goal is often to construct models that reflect the structures and parameters of some unobservable causal mechanism. The degree of isomorphis between such a theoretic model and a "true" model can be labeled "theoretic fit." In the absence of direct evidence that the researcher's theoretic model accurately reflects the true model, indices of "empirical fit" (Chi-Square, etc.) are used as indirect evidence of versimilitude. The issue addressed here is: Is empirical fit necessarily a good indicator of theoretic fit? This study uses simulation to compare the ability of Maximum Likelihood (ML) and Generalized Least Squares (GLS) estimation to provide theoretic fit in models that are parsimonious representations of a true model. We find that empirical fit using GLS was actually superior to that obtained when parameters in the incomplete model were constrained to the true values of the generating model. However, this apparent goodness of fit of GLS is obtained through greater distortion of the parameter estimates. In short, better empirical fit obtained for GLS, compared with ML, was obtained at the cost of lower theoretic fit. PMID- 26825129 TI - Fans' Judgments About the 1994-95 Major League Baseball Players' Strike. AB - In this study, we used a multilevel analysis to examine how strike tactics influenced fans' support of the 1994-95 Major League Baseball player's strike. Strike tactics were discounted ticket prices for season games, replacement players in games, and picket lines of striking players. Tactics were varied within judgment scenarios (i.e., baseball game announcements) and fans' responses to scenarios were used as within-person variables to estimate tactic influences. Fans' perceptions of themselves (e.g., extent of fanship) and the strike situation (e.g., extent to which the dispute was perceived as a labor dispute) were used as between-person variables to predict individual differences in tactic influences. Results indicated that more replacement players has a positive influence on support for the strike and higher discounted prices had a negative influence on strike support. The influences of replacement players on judgments was not associated with individual differences, whereas the influence of discounted prices on judgments did show such differences. The findings were used to discuss implications for winning support from consumers in a professional entertainment workers' strike. PMID- 26825130 TI - A Legitimate Case of Component Analysis of Ipsative Measures, and Partialling the Mean as an Alternative to Ipsatization. AB - Ipsatizing variable prior to component analysis, by subtracting the man score of each individual from all scores of that individual, has met with serious criticisms, both strategic and technical. On the other hand, the procedure is still popular in the study of personality, as a means of removing acquiescence variance. An attempt is made at reconciling these facts. Technical objections to component analysis of ipsatized variables, recently restated by Dunlap and Cornwall, are shown to be based on erroneous premises. A strategic objection leveled by Clemans does apply in a majority of cases, but has no bearing on the specific case of ipsatizing responses to personality questionnaires made up of opposite item pears. As an alternative to ipsatizing by subtraction of the mean, partialling the mean component is suggested as a more elegant procedure, allowing a breakdown of explained variance into variance due to the mean and to subequent components uncorrelated with the mean. PMID- 26825131 TI - Standard Errors for Matrix Correlations. AB - Matrix correlation is the index for the relationship between two sets of variables. Among the matrix correlations which have been proposed, the asymptotic standard errors of the following are derived: redundancy coefficient, Robert and Escoulfier's coefficient, Yanai's coefficient, Rozeboom's coefficient, and Coxhead's coefficient. With the assumption tha the variables are normall distributed, the standard errors of the coefficients are obtained using the delta method. Further, the standard errors of the congruence coefficients for two factor-loading matrices are obtained. The accuracies of their results are confirmed by simulation. PMID- 26825132 TI - Parachordal fistula--a case report and a short review. AB - Arteriovenous shunts of the neck and facial region rarely involve the external carotid artery and its branches. Most cases are considered to be iatrogenic or related to trauma but congenital shunts are rare. Parachordal arteriovenous fistulae are a group of embryologically derived arteriovenous shunts caused by defects involving the notochord, giving rise to cranial and paraspinal shunts. In the cranial regions, these shunts involve exclusively the metameric arteries- maxillary, ascending pharyngeal, occipital and vertebral. Signs and symptoms are variable, depending on the feeding vessel but also on the characteristics of the draining pathway. We report the case of a 17-year-old male patient with a shunt between the right internal maxillary artery and right external jugular vein detected at the age of 6, not associated with trauma, which we decided to treat because of an enlargement of the right cardiac atrium detected on routine examination. Digital subtraction angiography was performed to characterize the shunt followed by partial embolization with ballooning, coiling and Onyx injection. Echographic control 6 months after the procedure was compatible with complete occlusion of the shunt. We also perform a short review on this extremely rare entity. PMID- 26825133 TI - Rectal carcinoid tumor metastasis to a skull base meningioma. AB - Carcinoid tumors are rare, slow-growing neuroendocrine tumors that most frequently develop in the gastrointestinal tract or lungs and have high potential for metastasis. Metastasis to the brain is rare, but to another intracranial tumor is extremely rare. Of the intracranial tumors, meningiomas are the most common to host metastases, which may be related to its rich vascularity and E cadherin expression. We describe the case of a 65-year-old female with active chemotherapy-treated neuroendocrine carcinoma who presented with left-sided facial numbness, headaches, and blurry vision. Initial imaging revealed a 1 cm irregular dural-based left petrous apex mass suggestive of a meningioma that was re-imaged four months later as a rapidly enlarging, extra-axial, mass extending into the cavernous sinus, effacing Meckel's cave that resembled a trigeminal schwannoma. Pathology revealed a carcinoid tumor metastatic to meningioma. While the mass displayed characteristic imaging findings of a schwannoma, rapid growth in the setting of known active malignancy should prompt the clinician to consider mixed pathology from metastatic disease or a more aggressive meningioma. PMID- 26825134 TI - Intra-arterial nimodipine for cerebral vasospasm after subarachnoid haemorrhage: Influence on clinical course and predictors of clinical outcome. AB - Intra-arterial nimodipine (IAN) has shown a promising effect on cerebral vasospasm (CV) after aneurysmal subarachnoid haemorrhage. At our institution, Rigshospitalet, IAN treatment has been used since 2009, but the short- and long term clinical efficacy of IAN has not yet been assessed. The purpose was to evaluate the efficacy and clinical outcome of IAN treatment of symptomatic CV, and to assess the predictors of clinical outcome. Medical records of 25 patients undergoing a total of 41 IAN treatment sessions were retrospectively reviewed. Data on angiographic results, blood-flow velocities and the clinical condition before and after the IAN treatment were recorded. Predictors of the clinical outcome were assessed with a linear regression model. Positive angiographic response was achieved in 95.1% of 41 IAN treatment sessions. Flow-velocity measurements showed no relationship with angiographic responses of IAN. The immediate clinical improvement was observed in three patients (12%). Five patients (20%) had a favourable outcome at discharge and at three-month follow up; 10 patients (40%) had a moderate to poor outcome; and the rest (40%) died. Increased number of affected vessels and number of procedures carried out per patient, and a trend toward an increased delay time from symptomatic CV to confirming angiographic CV and thus instituting IAN treatment predicted the poor clinical outcome. IAN treatment appears to be effective in reversing angiographic CV. However, it is not always effective in reversing clinical deterioration, as several other factors including treatment delay affect the clinical course. PMID- 26825135 TI - Internal carotid artery stenosis with persistent primitive hypoglossal artery treated with carotid artery stenting: A case report and literature review. AB - Persistent primitive hypoglossal artery (PPHA) is a persistent carotid-basilar anastomosis. It rarely remains at birth. It occasionally may be a risk for ischemia and embolic infarction to the posterior cerebral circulation, especially in patients with carotid stenosis proximal to the origin of persistent primitive arteries. We describe a case of a 60-year-old woman with asymptomatic internal carotid artery (ICA) stenosis and ipsilateral PPHA successfully treated by carotid artery stenting (CAS). A few cases of CAS for ICA stenosis with PPHA have been reported, but the strategy and methods in each case were different because of its unique anatomy and hemodynamics. It is essential to prevent distal embolisms and preserve blood flow at the territory of both the ICA and PPHA. The protection method should be selected carefully. We review the literature and discuss appropriate treatment strategies. PMID- 26825136 TI - Compressive hematoma and deep arteriovenous malformation: Emergency endovascular occlusion via a venous approach with surgical evacuation of the hematoma. AB - Compressive hematoma associated with deep arterio-venous malformation is a difficult surgery. Arterial presurgical embolization is often indicated but rarely effective. Endovascular occlusion via a venous approach is a technique that has recently been undertaken successfully to treat certain types of sub-pial vascular malformation. The venous endovascular approach has succeeded in a 20 year-old man of who presented with a compressive hematoma due to rupture of a deep arteriovenous malformation. By fully endovascular occlusion, the surgery consisted of surgical removal of the hematoma, with reduced cortical damage. PMID- 26825137 TI - Developing a Tablet-Based Self-Persuasion Intervention Promoting Adolescent HPV Vaccination: Protocol for a Three-Stage Mixed-Methods Study. AB - BACKGROUND: Human papillomavirus (HPV)-related cancers are a significant burden on the US health care system that can be prevented through adolescent HPV vaccination. Despite guidelines recommending vaccination, coverage among US adolescents is suboptimal particularly among underserved patients (uninsured, low income, racial, and ethnic minorities) seen in safety-net health care settings. Many parents are ambivalent about the vaccine and delay making a decision or talking with a provider about it. Self-persuasion-generating one's own arguments for a health behavior-may be particularly effective for parents who are undecided or not motivated to make a vaccine decision. OBJECTIVE: Through a 3-stage mixed methods protocol, we will identify an optimal and feasible self-persuasion intervention strategy to promote adolescent HPV vaccination in safety-net clinics. METHODS: In Stage 1, we will define content for a tablet-based self persuasion app by characterizing (1) parents' self-generated arguments through cognitive interviews conducted with parents (n=50) of patients and (2) parent provider HPV vaccine discussions through audio recordings of clinic visits (n=50). In Stage 2, we will compare the effects of the four self-persuasion intervention conditions that vary by cognitive processing level (parents verbalize vs listen to arguments) and choice of argument topics (parents choose vs are assigned topics) on parental vaccine intentions in a 2 * 2 factorial design randomized controlled trial (n=160). This proof-of-concept trial design will identify which intervention condition is optimal by quantitatively examining basic self-persuasion mechanisms (cognitive processing and choice) and qualitatively exploring parent experiences with intervention tasks. In Stage 3, we will conduct a pilot trial (n=90) in the safety-net clinics to assess feasibility of the optimal intervention condition identified in Stage 2. We will also assess its impact on parent-provider discussions. RESULTS: This paper describes the study protocol and activities to date. Currently, we have developed the initial prototype of the tablet app for English- and Spanish-speaking populations, and completed Stage 1 data collection. CONCLUSIONS: Our systematic collaboration between basic and applied behavioral scientists accelerates translation of promising basic psychological research into innovative interventions suitable for underserved, safety-net populations. At project's end, we plan to have a feasible and acceptable self-persuasion intervention that can affect key cancer disparities in the United States through prevention of HPV related cancers. TRIAL REGISTRATION: ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/NCT02537756 and http://clinicaltrials.gov/ct2/show/NCT02535845 (Archived by WebCite at http://www.webcitation.org/6e5XcOGXz and http://www.webcitation.org/6e5XfHoic, respectively). PMID- 26825138 TI - Metabolic syndrome: genetic insights into disease pathogenesis. AB - PURPOSE OF REVIEW: Metabolic syndrome (MetS) is a cluster of interrelated and heritable metabolic traits, which collectively impart unsurpassed risk for atherosclerotic cardiovascular disease and type 2 diabetes. Considerable work has been done to understand the underlying disease mechanisms by elucidating its genetic cause. RECENT FINDINGS: Genome-wide association studies have been widely utilized albeit with modest success in identifying variants that are associated with more than two metabolic traits. Another limitation of this approach is the inherent small effect of the common variants, a major barrier for dissecting their cognate pathways. Modest advances in this venue have been also made by genetic studies of kindreds at the extreme ends of quantitative distributions. These efforts have led to the discovery of a number of disease genes with large effects that underlie the association of diverse traits of this syndrome. SUMMARY: Substantial progress has been made over the last decade in identification of genetic risk factors associated with the various traits of MetS. The heterogeneity and multifactorial heritability of MetS, however, has been a challenge toward understanding the factors underlying the association of these traits. Genetic investigations of outlier kindreds or homogenous populations with high prevalence for the disease can potentially improve our knowledge of the disease pathophysiology. PMID- 26825139 TI - Environmental persistence of Tulane virus - a surrogate for human norovirus. AB - Human noroviruses (HuNoVs) are the leading cause of acute viral gastroenteritis worldwide. The persistence of HuNoV in the environment contributes significantly to its transmission to humans. Surrogate viruses are used to study HuNoV owing to the lack of a cell culture system for this virus. Here, the persistence of Tulane virus (TV) - a novel HuNoV surrogate - in surface water (SW) and groundwater (GW) as well as on acrylic-based solid (ABS) and stainless steel (SS) surfaces was investigated. After 28 days, TV remained stable in SW (<1 log10 reduction) but was reduced by >=3.5 to 4 log10 in GW by day 21. TV had a higher rate of reduction on SS compared with ABS, with corresponding D values of 18.5 +/- 0.34 and 13.1 +/- 0.36 days, respectively. This is the first study to demonstrate the persistence of TV in environmental waters and on fomite surfaces. PMID- 26825140 TI - Short-Term Absenteeism and Health Care Utilization Due to Lower Extremity Injuries Among Novice Runners: A Prospective Cohort Study. AB - OBJECTIVE: To describe absenteeism and health care utilization (HCU) within 6 weeks after occurrence of running-related injuries (RRIs) among novice runners and to explore differences relating to injury and personal characteristics. DESIGN: Prospective cohort study. SETTING: Primary care. PARTICIPANTS: One thousand six hundred ninety-six novice runners (18-65 years) participating in a 6 week running program ("Start-to-Run"). MAIN OUTCOME MEASURES: Injury characteristics were assessed by weekly training logs and personal characteristics by a baseline questionnaire. Data on absenteeism and HCU were collected using questionnaires at 2 and 6 weeks after the RRI occurred. RESULTS: A total of 185 novice runners (11%) reported an RRI during the 6-week program. Of these injured novice runners, 78% reported absence from sports, whereas only 4% reported absence from work. Fifty-one percent of the injured novice runners visited a health care professional, mostly physical therapists (PTs) rather than physicians. Absenteeism was more common among women than men and was also more common with acute RRIs than gradual-onset RRIs. As regards HCU, both the variety of professionals visited and the number of PT visits were higher among runners with muscle-tendon injuries in the ankle/foot region than among those with other RRIs. CONCLUSIONS: Among novice runners sustaining an RRI during a 6-week running program, over three quarters reported short-term absence from sports, whereas absence from work was very limited, and over half used professional health care. Both absence and HCU are associated with injury characteristics. CLINICAL RELEVANCE: In future running promotion programs (eg in Start-to-Run programs), specific attention should be paid to acute injuries and to muscle-tendon injuries in the ankle/foot region. PMID- 26825141 TI - Bone Structure and Geometric Properties at the Radius and Tibia in Adolescent Endurance-Trained Cyclists. AB - OBJECTIVE: To describe cortical and trabecular volumetric bone mineral density (vBMD), bone mineral content (BMC), cross-sectional area (CSA), and bone strength indexes (BSIs) in adolescent endurance-trained cyclists (CYC) and compare them with controls (CON). DESIGN: Descriptive cohort study. PARTICIPANTS: Twenty-five male adolescent CYC and 17 CON. ASSESSMENT OF RISK FACTORS: Peripheral quantitative computed tomography was used to evaluate proximal and distal sites of the radius and tibia. MAIN OUTCOME MEASURES: Total, trabecular, and cortical BMC, vBMD, and CSA were measured. Also, cortical thickness, endosteal and periosteal circumferences, and different BSIs were calculated. Unadjusted analysis of variance and body weight-adjusted analysis of covariance tests were applied between cyclist and control groups. RESULTS: Cyclists were almost 12% lighter than CON (P < 0.05). Unadjusted data showed lower distal total vBMD and proximal cortical BMC and vBMD in cyclists compared with CON at the radius (P < 0.05) and lower distal total and trabecular BMC, vBMD and bone area, proximal total and cortical BMC and vBMD, and cortical bone area at the tibia (P < 0.05). Body weight-adjusted data showed the same differences for distal total vBMD at the radius and total and trabecular BMC and vBMD at the tibia, diaphyseal radius cortical vBMD and tibia total vBMD, cortical BMC and area, and also for tibia cortical thickness and BSI. The rest of differences were no longer detectable and bone area at the distal radius become significantly higher in cyclist compared with CON (P < 0.05). CONCLUSIONS: Adolescent CYC in this study showed lower values of BMC and vBMD at determined sites of the radius and tibia than CON, some of these differences were explained in part by their lower body weight. However, even further adjustment, some differences remained, which indicates that further longitudinal studies are needed to better understand if cycling influences these differences. PMID- 26825142 TI - Comparative Evaluation of Statistical and Mechanistic Models of Escherichia coli at Beaches in Southern Lake Michigan. AB - Statistical and mechanistic models are popular tools for predicting the levels of indicator bacteria at recreational beaches. Researchers tend to use one class of model or the other, and it is difficult to generalize statements about their relative performance due to differences in how the models are developed, tested, and used. We describe a cooperative modeling approach for freshwater beaches impacted by point sources in which insights derived from mechanistic modeling were used to further improve the statistical models and vice versa. The statistical models provided a basis for assessing the mechanistic models which were further improved using probability distributions to generate high-resolution time series data at the source, long-term "tracer" transport modeling based on observed electrical conductivity, better assimilation of meteorological data, and the use of unstructured-grids to better resolve nearshore features. This approach resulted in improved models of comparable performance for both classes including a parsimonious statistical model suitable for real-time predictions based on an easily measurable environmental variable (turbidity). The modeling approach outlined here can be used at other sites impacted by point sources and has the potential to improve water quality predictions resulting in more accurate estimates of beach closures. PMID- 26825143 TI - More on autoimmune hepatitis and acute hepatitis A. PMID- 26825144 TI - Risperidone-induced hepatotoxicity in a patient addicted to synthetic cannabinoid. PMID- 26825145 TI - CALR mutations in Chinese Budd-Chiari syndrome patients. PMID- 26825146 TI - Re: Patient and physician preferences for the treatment of chronic hepatitis C virus infections: does the perspective matter? (Eur J Gastroenterol Hepatol 2015, 27:1063-1068). PMID- 26825147 TI - Acid-base disturbance in liver cirrhosis. PMID- 26825149 TI - Use of Intensive Care Services for Medicare Beneficiaries Undergoing Major Surgical Procedures. AB - BACKGROUND: Use of intensive care after major surgical procedures and whether routinely admitting patients to intensive care units (ICUs) improve outcomes or increase costs is unknown. METHODS: The authors examined frequency of admission to an ICU during the hospital stay for Medicare beneficiaries undergoing selected major surgical procedures: elective endovascular abdominal aortic aneurysm (AAA) repair, cystectomy, pancreaticoduodenectomy, esophagectomy, and elective open AAA repair. The authors compared hospital mortality, length of stay, and Medicare payments for patients receiving each procedure in hospitals admitting patients to the ICU less than 50% of the time (low use), 50 to 89% (moderate use), and 90% or greater (high use), adjusting for patient and hospital factors. RESULTS: The cohort ranged from 7,878 patients in 162 hospitals for esophagectomies to 69,989 patients in 866 hospitals for endovascular AAA. Overall admission to ICU ranged from 35.6% (endovascular AAA) to 71.3% (open AAA). Admission to ICU across hospitals ranged from less than 5% to 100% of patients for each surgical procedure. There was no association between hospital use of intensive care and mortality for any of the five surgical procedures. There was a consistent association between high use of intensive care with longer length of hospital stay and higher Medicare payments only for endovascular AAA. CONCLUSIONS: There is little consensus regarding the need for intensive care for patients undergoing major surgical procedures and no relationship between a hospital's use of intensive care and hospital mortality. There is also no consistent relationship across surgical procedures between use of intensive care and either length of hospital stay or payments for care. PMID- 26825150 TI - Intensive Care after High-risk Surgery: What's in a Name? PMID- 26825151 TI - Preoperative Laboratory Investigations: Rates and Variability Prior to Low-risk Surgical Procedures. AB - BACKGROUND: Increasing attention has been focused on low-value healthcare services. Through Choosing Wisely campaigns, routine laboratory testing before low-risk surgery has been discouraged in the absence of clinical indications. The authors investigated rates, determinants, and institutional variation in laboratory testing before low-risk procedures. METHODS: Patients who underwent ophthalmologic surgeries or predefined low-risk surgeries in Ontario, Canada, between April 1, 2008, and March 31, 2013, were identified from population-based administrative databases. Preoperative blood work was defined as a complete blood count, prothrombin time, partial thromboplastin, or basic metabolic panel within 60 days before an index procedure. Adjusted associations between patient and institutional factors and preoperative testing were assessed with hierarchical multivariable logistic regression. Institutional variation was characterized using the median odds ratio. RESULTS: The cohort included 906,902 patients who underwent 1,330,466 procedures (57.1% ophthalmologic and 42.9% low-risk surgery) at 119 institutions. Preoperative blood work preceded 400,058 (30.1%) procedures. The unadjusted institutional rate of preoperative blood work varied widely (0.0 to 98.1%). In regression modeling, significant predictors of preoperative testing included atrial fibrillation (adjusted odds ratio [AOR], 2.58; 95% CI, 2.51 to 2.66), preoperative medical consultation (AOR, 1.68; 95% CI, 1.65 to 1.71), previous mitral valve replacement (AOR, 2.33; 95% CI, 2.10 to 2.58), and liver disease (AOR, 1.69; 95% CI, 1.55 to 1.84). The median odds ratio for interinstitutional variation was 2.43. CONCLUSIONS: Results of this study suggest that testing is associated with a range of clinical covariates. However, an association was similarly identified with preoperative consultation, and significant variation between institutions exists across the jurisdiction. PMID- 26825152 TI - If I Had a Hammer: Building Alignment and Accountability. PMID- 26825153 TI - Low Serum Concentrations of Rifampicin and Pyrazinamide Associated with Poor Treatment Outcomes in Children with Tuberculosis Related to HIV Status. AB - OBJECTIVES: To compare the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) between HIV-infected and HIV-uninfected children with tuberculosis (TB) and correlate it with TB treatment outcome. METHODS: HIV uninfected (n = 84) and HIV-infected (n = 77) children with TB receiving standard thrice weekly treatment were recruited from 6 hospitals in India. Semi-intensive pharmacokinetic sampling was performed during intensive phase of TB treatment after directly observed administration of drugs. Drug concentrations were measured by high performance liquid chromatography. INH acetylator status was determined, and nutritional assessment was done. Children were followed-up and treatment outcomes noted. RESULTS: Children with HIV and TB had significantly lower RMP peak concentration (Cmax) (2.6 vs. 5.1 MUg/mL; P < 0.001) and exposure [area under the time-concentration curve (AUC0-8); 10.4 vs. 23.4 MUg/mL h; P < 0.001] than those with TB. Among HIV-infected children, a significantly higher proportion had stunting (77% vs. 29%; P < 0.001) and underweight (73% vs. 38%; P < 0.001) compared with children with TB. Combining both groups, RMP Cmax (P = 0.001; adjusted odds ratio = 1.437; 95% confidence interval: 1.157-1.784) and PZA Cmax (P = 0.027; adjusted odds ratio = 1.041; 95% confidence interval: 1.005 1.079) significantly influenced treatment outcome. CONCLUSIONS: HIV infection was associated with lower Cmax of RMP and INH and AUC0-8 of RMP. Over 90% of children in both groups had subtherapeutic RMP Cmax. Cmax of RMP and PZA significantly influenced TB treatment outcome in children with TB. The findings have important clinical implications and suggest the need to increase anti-TB drug doses in children with HIV and TB. PMID- 26825154 TI - Pediatric Invasive Pneumococcal Disease in Guatemala City: Importance of Serotype 2. AB - INTRODUCTION: To inform estimations of the potential impact of recently introduced pneumococcal conjugate vaccine (PCV), we report results of 11 years of pre-PCV surveillance for invasive pneumococcal disease (IPD) among children in Guatemala City. METHODS: Cases of IPD in children younger than 5 years were identified by active surveillance at 3 referral hospitals in Guatemala City from October 1996 through 2007. Clinical and demographic data were obtained, and isolates of Streptococcus pneumoniae from normally sterile sites were serotyped using latex agglutination and confirmed by Quellung reaction. RESULTS: Four hundred fifty-two cases of IPD were identified with a case fatality rate of 21%. Meningitis was the most common cause of death (77% of all deaths) and occurred more often in infancy (median age 5 months) than other clinical syndromes. Of the 137 isolates serotyped, type 1 (26 cases, 17%), type 2 (25 cases, 16%) and type 5 (18 cases, 12%) were the most common. Serotype 2 was associated with a higher case fatality rate (28%), higher rate of meningitis (68%) and occurred in younger infants (median age, 3.5 months) than other common serotypes. Recently introduced PCV13 includes 73% of observed serotypes in the study. CONCLUSION: Infants with IPD presented at a young age. Serotype 2, rarely reported as a significant cause of IPD and not included in available PCVs, was a common cause of disease in this population. PCV13 introduction in Guatemala, begun in 2013, may not have as great an impact in disease reduction as has been observed in other countries. PMID- 26825155 TI - Skin Biopsy in Netherton Syndrome: A Histological Review of a Large Series and New Findings. AB - Netherton syndrome (NS) is a severe genetic skin disorder, with often delayed or misleading clinical signs. The histological features of skin biopsies, usually described as a psoriasiform hyperplasia, have only been reported in isolated case reports or small case series. The aim of this study is to define, for the first time, the precise histological pattern of cutaneous lesions, in a large cohort of skin biopsies from confirmed NS patients. The study included 80 consecutive skin biopsies from 67 patients taken between January 1995 and June 2014. All were from confirmed NS patients with either a negative lympho-epithelial Kazal-type-related inhibitor (LEKTI) immunohistochemistry and/or molecular confirmation by identified mutation in SPINK5. In this cohort, the most frequent histological finding was also psoriasiform hyperplasia, but there were additional, less common, or previously unreported findings, including compact parakeratosis with large nuclei, subcorneum or intracorneum splitting, presence of clear cells in the upper epidermis or stratum corneum, dyskeratosis, dermal infiltrate with neutrophils and/or eosinophils, and dilated blood vessels in the superficial dermis. An early confirmation of the diagnosis of NS is essential for improved patient management. Thus, in the situation of a patient with an unknown skin disorder and non specific clinical presentation, the dermatopathologist may now be able to suggest the diagnosis of NS based on these newly reported characteristics. However, LEKTI immunohistochemistry remains the essential diagnostic investigation in cases with misleading or nonspecific histological features and is mandatory for the definitive diagnosis of NS in all patients. PMID- 26825156 TI - Immunohistochemistry in Dermatopathology: A Retrospective Study of the Most Frequently Used Antibodies. AB - Immunohistochemistry (IHC) is an ancillary technique to improve diagnostic accuracy and prognosis in histopathology of both inflammatory and neoplastic cutaneous disorders. However, only a few studies address specifically the set of antibodies available for inflammatory or neoplastic skin diseases. In this study, we analyzed the IHC studies performed for inflammatory and neoplastic skin disorders in cutaneous biopsies taken in our department during 1 year. From a total of 8579 skin biopsies performed throughout the year 2011 in our department, IHC studies were performed in 283 cutaneous biopsies. The total number of different antibodies used in the IHC studies of those 283 skin biopsies was 129. These antibodies were used in 1421 studies, with a mean of 5 cases per antibody studied. The proliferative marker MIB-1 was the single antibody with the highest number of studies, with a total of 119 (8.3% of all IHC studies performed), followed by 113 of CD3 (7.9% of total IHC studies) and 108 of Melan-A (7.6% of total IHC studies). Other hematopoietic differentiation markers, such as CD20, CD4, and CD8, and other melanocytic markers, such as S-100 protein, Melan-A, and HMB-45, were all investigated with a frequency greater than 50 studies each. The 2 most frequent categories were melanocytic neoplasms, which represented 25% of all specimens studied by IHC, and the proliferations of lymphohematopoietic nature, which were 20% of all studied samples and represented by far the highest number of IHC stains per case to reach a final diagnosis. Both previous categories together accounted for 45% of all diagnoses in which IHC was performed. We compare our results with the only similar study previously published in the literature. The gold standard panel of antibodies that should be available in everyday practice in dermatopathology to arrive at a specific diagnosis in each cutaneous inflammatory disease or neoplastic process involving the skin is still a matter of discussion. PMID- 26825158 TI - "Eruptive Lentiginosis" in a Patient With Vitiligo and Inflammatory Bowel Disease Treated With Azathioprine. AB - Multiple lentiginosis are seen in many multisystemic diseases and during the course of many treatment schemes in the area of application of topical substances, PUVA, or more disseminated reactions in the case of systemic drugs. We report a case of a 67-year-old man with multiple comorbidities including vitiligo, and a recent diagnosis of inflammatory bowel disease, who developed millimeter-size, circular, brown macules in photoexposed areas both affected and not affected by vitiligo while was taken azathioprine, which disappeared after drug withdrawal. Biopsy showed groups of apoptotic keratinocytes, basal hyperpigmentation, and slight dermal inflammation. The authors describe "eruptive lentiginosis" as an adverse event of azathioprine not previously described in the literature. PMID- 26825159 TI - First Reported Case of Postirradiation Pseudosclerodermatous Panniculitis After Stereotactic Body Radiation Therapy for the Treatment of Non-Small Cell Lung Cancer. AB - Postirradiation pseudosclerodermatous panniculitis is a rare complication of radiation therapy that presents as an indurated plaque and/or subcutaneous nodule in an area of previously irradiated tissue. The histopathologic pattern is of mixed lobular and septal panniculitis with necrotic adipocytes and thickened sclerotic septa as well as dense inflammatory infiltrates consisting mainly of histiocytes. The typical time interval is 1 month to several years after treatment with radiation therapy. This is a case of an 86-year-old man with a medical history significant for diffuse large B-cell lymphoma who was given 3 fractions of stereotactic body radiation therapy for treatment of stage IA non small cell lung adenocarcinoma of the right upper lobe. Two years later, he presented with several small palpable subcutaneous right axillary nodules, which coalesced into a 6-cm firm multilobulated right axillary mass over several weeks. Histopathology showed sclerosing panniculitis with lipomembranous changes and septal fibrosis. This is the first reported case describing postirradiation pseudosclerodermatous panniculitis in a patient with lung cancer treated with stereotactic body radiation therapy. This diagnosis must be differentiated from other subtypes of panniculitis and complications of radiation therapy. PMID- 26825160 TI - Pyoderma Vegetans Misdiagnosed as Verrucous Carcinoma. AB - Pyoderma vegetans, a rare disorder of the skin, is considered a highly specific marker for inflammatory bowel disease, especially ulcerative colitis. It is clinically characterized by large verrucous plaques with elevated borders and multiple pustules. Here, the authors report the case of a 33-year-old man who was misdiagnosed as having verrucous carcinoma for 4 years. PMID- 26825161 TI - Bleeding Papule on the Scapula. PMID- 26825162 TI - A Modern Approach to Differential Diagnosis Between Cutaneous Apocrine Carcinoma and Metastasis From Breast Carcinoma. PMID- 26825163 TI - Epidermolytic Acanthoma of the Genitalia Does Not Show Mutations in KRT1 or KRT10. PMID- 26825164 TI - MITF Positivity in Atypical Fibroxanthoma. PMID- 26825165 TI - A Digital Squamous Cell Carcinoma Mimicking a Diabetic Foot Ulcer, With Early Inguinal Metastasis and Cancer-Related Lymphedema. AB - Although squamous cell carcinoma (SCC) is the second most common nonmelanoma skin cancer, clinicians have difficulty diagnosing SCC of the toe because its clinical features can mimic other less serious diseases. Clinicians are especially prone to misdiagnose SCC of the toe as diabetic foot ulcer in patients with diabetes mellitus because of the clinical similarity of the 2 ailments. SCC of the toe is generally considered to have a low risk of metastasis. Locoregional or distant metastases without bone or tendon involvement are particularly rare. The authors report here an interesting case of rapidly spreading SCC of the toe with metastasis to multiple lymph nodes and cancer-related lymphedema. Physicians should be aware of the possibility of malignancy when they encounter chronic and recalcitrant ulcerative lesions of the digits. PMID- 26825166 TI - Neutrophilic Dermatosis Limited to Lipo-Lymphedematous Skin in a Morbidly Obese Woman on Dasatinib Therapy. AB - Neutrophilic dermatosis (ND) confined to postmastectomy lymphedema, localized Sweet syndrome, is a newly recognized disease. In this study, the authors describe a 44-year-old obese woman with chronic myelogenous leukemia in molecular remission on dasatinib therapy, who presented with a painful urticarial eruption limited to lipo-lymphedematous skin and accompanied by malaise, episodic fever, diarrhea, neutrophilia, and leukocytosis. Initially transient and migratory, the rash became fixed, papular, and vesicular and showed minimal response to corticosteroids. Biopsy demonstrated sparse perivascular and interstitial dermal neutrophilic infiltrates, without vasculitis or significant dermal edema. Aggregates of neutrophils were found within and surrounding lymphangiectases. Biopsy of a new onset papule 3 weeks later demonstrated papillary dermal edema, denser neutrophilic infiltrate, and vasculitis-like changes. These 2 histopathologic patterns of ND, early and late, resemble neutrophilic urticarial dermatitis (also known as neutrophilic dermatitis with systemic inflammation) and Sweet syndrome, respectively. Extensive workup did not reveal evidence of relapsed chronic myelogenous leukemia, infection, or a coexisting systemic inflammatory disease. Dasatinib was discontinued and the eruption gradually resolved over 2.5 months. Still in molecular remission (no detectable BCR-ABL gene fusion), dasatinib therapy was recommenced at 3-month follow-up. After 10 months, she complains of malaise and arthralgia, but no cutaneous symptoms. The evolution and slow resolution of this ND in lipo-lymphedematous skin implicate poor lymphatic clearance of factors, antigenic and/or toxic, involved in the pathogenesis of ND. PMID- 26825167 TI - From Expert Clinician to Nurse Educator: Outcomes of a Faculty Academy Initiative. AB - The Eastern Shore Faculty Academy and Mentorship Initiative, a collaborative program among 3 nursing programs in rural Maryland, was developed to facilitate the transition of expert clinicians from diverse backgrounds in clinical specialty areas with critical shortages to new roles as part-time clinical faculty. Initial outcomes include 32 Academy graduates, with 37.5% representing diverse backgrounds and 37.5% in needed clinical specialties. This initiative represents an innovative approach to meeting the challenges of the nursing faculty shortage through collaborative efforts and creative solutions. PMID- 26825168 TI - The interaction between blood pressure variability, obesity, and left ventricular mechanics: findings from the hypertensive population. AB - OBJECTIVE: The aim of this study was to determine the relationship between blood pressure (BP) variability and left ventricular (LV) mechanical function in untreated normal-weight, overweight, and obese hypertensive patients. METHODS: This cross-sectional study included 144 untreated hypertensive study participants who underwent 24-h ambulatory BP monitoring and complete two (2DE) and three dimensional echocardiography (3DE). All the patients were divided into three groups according to their BMI: normal-weight patients (BMI < 25 kg/m), overweight patients (25 <= BMI < 30 kg/m), and obese patients (BMI >= 30 kg/m). RESULTS: Daytime, night-time, and 24-h BP variability progressively increased from normal weight, throughout overweight, to obese hypertensive study participants. 2DE and 3DE LV longitudinal, circumferential and radial strains, as well as 3DE area strain, were significantly lower in obese hypertensive patients than in normal weight and overweight study participants. 3DE LV volumes indexed for BSA did not differ significantly among the three observed groups. Night-time and 24 h BP variability indices, more than daytime BP variability parameters, were associated with 2DE and 3DE longitudinal and circumferential strains independent of BMI, LV mass index, and average 24-h SBP and DBP values. CONCLUSION: BP variability and LV deformation are significantly affected by obesity in untreated hypertensive patients. BP variability is associated with 2DE and 3DE LV mechanics independently of main clinical and echocardiographic characteristics. PMID- 26825169 TI - Candidate Antimetastasis Drugs Suppress the Metastatic Capacity of Breast Cancer Cells by Reducing Membrane Fluidity. AB - Despite the high mortality from metastatic cancer, therapeutic targets to prevent metastasis are limited. Efforts to identify genetic aberrations that predispose tumors to metastasis have been mostly unsuccessful. To understand the nature of candidate targets for metastatic disease, we performed an in silico screen to identify drugs that can inhibit a gene expression signature associated with epithelial-mesenchymal transition (EMT). Compounds discovered through this method, including those previously identified, appeared to restrict metastatic capacity through a common mechanism, the ability to modulate the fluidity of cell membranes. Treatment of breast cancer cell lines with the putative antimetastasis agents reduced membrane fluidity, resulting in decreased cell motility, stem cell like properties, and EMT in vitro, and the drugs also inhibited spontaneous metastasis in vivo When fluidity was unchanged, the antimetastasis compounds could no longer restrict metastasis, indicating a causal association between fluidity and metastasis. We further demonstrate that fluidity can be regulated by cellular cholesterol flux, as the cholesterol efflux channel ABCA1 potentiated metastatic behaviors in vitro and in vivo The requirement for fluidity was further supported by the finding in breast cancer patients that ABCA1 was overexpressed in 41% of metastatic tumors, reducing time to metastasis by 9 years. Collectively, our findings reveal increased membrane fluidity as a necessary cellular feature of metastatic potential that can be controlled by many currently available drugs, offering a viable therapeutic opportunity to prevent cancer metastasis. Cancer Res; 76(7); 2037-49. (c)2016 AACR. PMID- 26825170 TI - EGF816 Exerts Anticancer Effects in Non-Small Cell Lung Cancer by Irreversibly and Selectively Targeting Primary and Acquired Activating Mutations in the EGF Receptor. AB - Non-small cell lung cancer patients carrying oncogenic EGFR mutations initially respond to EGFR-targeted therapy, but later elicit minimal response due to dose limiting toxicities and acquired resistance. EGF816 is a novel, irreversible mutant-selective EGFR inhibitor that specifically targets EGFR-activating mutations arising de novo and upon resistance acquisition, while sparing wild type (WT) EGFR. EGF816 potently inhibited the most common EGFR mutations L858R, Ex19del, and T790M in vitro, which translated into strong tumor regressions in vivo in several patient-derived xenograft models. Notably, EGF816 also demonstrated antitumor activity in an exon 20 insertion mutant model. At levels above efficacious doses, EGF816 treatment led to minimal inhibition of WT EGFR and was well tolerated. In single-dose studies, EGF816 provided sustained inhibition of EGFR phosphorylation, consistent with its ability for irreversible binding. Furthermore, combined treatment with EGF816 and INC280, a cMET inhibitor, resulted in durable antitumor efficacy in a xenograft model that initially developed resistance to first-generation EGFR inhibitors via cMET activation. Thus, we report the first preclinical characterization of EGF816 and provide the groundwork for its current evaluation in phase I/II clinical trials in patients harboring EGFR mutations, including T790M. PMID- 26825171 TI - RASSF1A Directly Antagonizes RhoA Activity through the Assembly of a Smurf1 Mediated Destruction Complex to Suppress Tumorigenesis. AB - RASSF1A is a tumor suppressor implicated in many tumorigenic processes; however, the basis for its tumor suppressor functions are not fully understood. Here we show that RASSF1A is a novel antagonist of protumorigenic RhoA activity. Direct interaction between the C-terminal amino acids (256-277) of RASSF1A and active GTP-RhoA was critical for this antagonism. In addition, interaction between the N terminal amino acids (69-82) of RASSF1A and the ubiquitin E3 ligase Smad ubiquitination regulatory factor 1 (Smurf1) disrupted GTPase activity by facilitating Smurf1-mediated ubiquitination of GTP-RhoA. We noted that the RhoA binding domain of RASSF1A displayed high sequence homology with Rho-binding motifs in other RhoA effectors, such as Rhotekin. As predicted on this basis, RASSF1A competed with Rhotekin to bind RhoA and to block its activation. RASSF1A mutants unable to bind RhoA or Smurf1 failed to suppress RhoA-induced tumor cell proliferation, drug resistance, epithelial-mesenchymal transition, migration, invasion, and metastasis. Clinically, expression levels of RASSF1A and RhoA were inversely correlated in many types of primary and metastatic tumors and tumor cell lines. Collectively, our findings showed how RASSF1A may suppress tumorigenesis by intrinsically inhibiting the tumor-promoting activity of RhoA, thereby illuminating the potential mechanistic consequences of RASSF1A inactivation in many cancers. Cancer Res; 76(7); 1847-59. (c)2016 AACR. PMID- 26825172 TI - Secondary Tumors Arising in Patients Undergoing BRAF Inhibitor Therapy Exhibit Increased BRAF-CRAF Heterodimerization. AB - BRAF inhibitors (BRAFi) elicit therapeutic responses in metastatic melanoma, but alarmingly, also induce the formation of secondary benign and malignant skin tumors. Here, we report the emergence and molecular characterization of 73 skin and extracutaneous tumors in 31 patients who underwent BRAFi therapy. The majority of patients presented with classic epidermal tumors such as verrucous papillomas, keratoacanthomas, and squamous cell carcinomas (SCC). However, 15 patients exhibited new or rapidly progressing tumors distinct from these classic subtypes, such as lymph node metastasis, new melanomas, and genital and oral mucosal SCCs. Genotyping of the tumors revealed that oncogenic RAS mutations were found in 58% of the evaluable tumor samples (38/66) and 49% of the control tumors from patients not treated with BRAFi (30/62). Notably, proximity ligation assays demonstrated that BRAF-CRAF heterodimerization was increased in fixed tumor samples from BRAFi-treated patients compared with untreated patients. Our findings reveal that BRAF-CRAF complex formation is significantly associated with BRAFi treatment, and may therefore serve as a useful biomarker of BRAFi-induced cutaneous and extracutaneous tumor formation. PMID- 26825174 TI - Incidence of Profound Hypogammaglobulinemia and Infection Rate in Lymphoma Patients Following the Combination of Chemotherapy and Rituximab. AB - BACKGROUND: The Anti-CD20 monoclonal antibody Rituximab suppresses B-lymphocytes and may induce hypogammaglobulinemia in treated patients. The incidence and clinical significance of rituximab induced hypogammaglobulinemia in lymphoma patients is underestimated. METHODS: We retrospectively analyzed the rates of hypogammaglobulinemia, infection and infection-related mortality in 136 lymphoma patients who were treated with a combination of chemotherapy and rituximab. RESULTS: Rituximab given in more than 8 doses (OR 6.05, 95% CI: 1.24-29.5), relative hypogammaglobulinemia at time of lymphoma diagnosis (OR 4.2, 95% CI: 1.26-14.1) and the combination of fludarabine with rituximab (OR 3.4, 95% CI: 1.24-9.47) were factors significantly associated with prolonged (more than 6 months) hypogammaglobulinemia. The combination of fludarabine and rituximab (OR 6.4, 95% CI: 1.49-27.0) and secondarily prolonged hypogammaglobulinemia (OR 4.5, 95% CI: 1.19-18.5) were found to be predictive factors for severe infections and infection-related mortality. CONCLUSION: These data suggest the importance of following serum immunoglobulin levels before and after combination immuno chemotherapy, particularly in patients with recurrent infections or relapsed/refractory disease. PMID- 26825175 TI - Potential Crossreactivity of Human Immune Responses Against HCMV Glycoprotein B. AB - Antigens of infectious agents share amino acid sequences with human proteins. Such a peptide matching may lead to autoimmunity through crossreactivity phenomena following pathogen infection and/or immunotherapeutic approaches. In this framework, we analyzed as a model the primary sequence of human cytomegalovirus (HCMV) glycoprotein B (gB) protein and searched for viral peptide sequences shared with human proteins. We show that the HCMV antigen has a high peptide identity with a large number of human proteins at the penta-, hexa-, and heptapeptide level, with the viral versus human peptide overlap involving host proteins implicated in crucial processes such as embryonic development, spermatogenesis, spatial learning, and hippocampal plasticity, inter alia. This study might help understand the etiology of the pathologic sequela associated with HCMV (re)activation and, in addition, address scientific and clinical research toward the definition of antiviral therapeutics based on non crossreactive viral sequences. PMID- 26825173 TI - Breast Tumor Kinase (Brk/PTK6) Is Induced by HIF, Glucocorticoid Receptor, and PELP1-Mediated Stress Signaling in Triple-Negative Breast Cancer. AB - Cancer cells use stress response pathways to sustain their pathogenic behavior. In breast cancer, stress response-associated phenotypes are mediated by the breast tumor kinase, Brk (PTK6), via the hypoxia-inducible factors HIF-1alpha and HIF-2alpha. Given that glucocorticoid receptor (GR) is highly expressed in triple negative breast cancer (TNBC), we investigated cross-talk between stress hormone driven GR signaling and HIF-regulated physiologic stress. Primary TNBC tumor explants or cell lines treated with the GR ligand dexamethasone exhibited robust induction of Brk mRNA and protein that was HIF1/2-dependent. HIF and GR coassembled on the BRK promoter in response to either hypoxia or dexamethasone, indicating that Brk is a direct GR/HIF target. Notably, HIF-2alpha, not HIF 1alpha, expression was induced by GR signaling, and the important steroid receptor coactivator PELP1 was also found to be induced in a HIF-dependent manner. Mechanistic investigations showed how PELP1 interacted with GR to activate Brk expression and demonstrated that physiologic cell stress, including hypoxia, promoted phosphorylation of GR serine 134, initiating a feed-forward signaling loop that contributed significantly to Brk upregulation. Collectively, our findings linked cellular stress (HIF) and stress hormone (cortisol) signaling in TNBC, identifying the phospho-GR/HIF/PELP1 complex as a potential therapeutic target to limit Brk-driven progression and metastasis in TNBC patients. PMID- 26825176 TI - Combination Social Protection for Reducing HIV-Risk Behavior Among Adolescents in South Africa. AB - BACKGROUND: Social protection (ie, cash transfers, free schools, parental support) has potential for adolescent HIV prevention. We aimed to identify which social protection interventions are most effective and whether combined social protection has greater effects in South Africa. METHODS: In this prospective longitudinal study, we interviewed 3516 adolescents aged 10-18 between 2009 and 2012. We sampled all homes with a resident adolescent in randomly selected census areas in 4 urban and rural sites in 2 South African provinces. We measured household receipt of 14 social protection interventions and incidence of HIV-risk behaviors. Using gender-disaggregated multivariate logistic regression and marginal effects analyses, we assessed respective contributions of interventions and potential combination effects. RESULTS: Child-focused grants, free schooling, school feeding, teacher support, and parental monitoring were independently associated with reduced HIV-risk behavior incidence (odds ratio: 0.10-0.69). Strong effects of combination social protection were shown, with cumulative reductions in HIV-risk behaviors. For example, girls' predicted past-year incidence of economically driven sex dropped from 11% with no interventions to 2% among those with a child grant, free school, and good parental monitoring. Similarly, girls' incidence of unprotected/casual sex or multiple partners dropped from 15% with no interventions to 10% with either parental monitoring or school feeding, and to 7% with both interventions. CONCLUSION: In real world, high-epidemic conditions, "combination social protection," shows strong HIV prevention effects for adolescents and may maximize prevention efforts. PMID- 26825177 TI - HIV Community Viral Load and Factors Associated With Elevated Viremia Among a Community-Based Sample of Men Who Have Sex With Men in Vancouver, Canada. AB - BACKGROUND: We developed estimates of community viral load (VL) and risk factors for unsuppressed VL from a cross-sectional study of men who have sex with men (MSM) in Vancouver, Canada. METHODS: MSM were recruited from February 25, 2012 to February 28, 2014 using respondent-driven sampling (RDS). Participants completed a computer-assisted self-interview questionnaire and a nurse-administered point of-care HIV test. For HIV-positive participants, we conducted VL and CD4 cell counts. We used RDS-weighted analysis to obtain population estimates of key variables and multivariable logistic regression to examine factors associated with having a VL of >=200 copies per milliliter among HIV-positive participants. RESULTS: We recruited 719 participants, of whom 119 (16.6%) were seeds. Our estimate of the population prevalence of HIV was 23.4% [95% confidence interval (CI): 15.8% to 31.0%] after RDS adjustments. We estimated that 18.6% (95% CI: 8.8% to 30.4%) of HIV-positive MSM in Vancouver had a VL of >=200 copies per milliliter. Having an unsuppressed VL was associated with non-white ethnicity [adjusted odds ratio (AOR) = 4.34; 95% CI: 1.67 to 11.1], an annual income of <$15,000 CAD (AOR = 6.43; 95% CI: 2.08 to 19.9), using gamma-hydroxy butyrate in the previous 6 months (AOR = 4.85; 95% CI: 1.79 to 13.2), unprotected anal intercourse with a known HIV-negative or an unknown serostatus partner (AOR = 3.13; 95% CI: 1.10 to 8.90), and disclosing one's HIV serostatus >=50% of the time (AOR = 7.04; 95% CI: 1.01 to 49.1). CONCLUSION: Despite a high prevalence of HIV, we estimated that a small proportion of HIV-positive MSM have undiagnosed HIV and unsuppressed VL. Our results highlight the importance of continued work to address health inequities using a framework based on social determinants of health. PMID- 26825178 TI - Brief Report: Macrophage Activation in HIV-2-Infected Patients Is Less Affected by Antiretroviral Treatment-sCD163 in HIV-1, HIV-2, and HIV-1/2 Dually Infected Patients. AB - The course of disease among HIV-2, HIV-1, and HIV-1/2 dually infected patients is different. We investigated the macrophage activation marker soluble CD163 (sCD163) dynamics in 212 HIV-1, HIV-2, and HIV-1/2 dually infected patients. There were no differences in sCD163 levels at baseline or during follow-up without antiretroviral therapy (ART). At follow-up on ART, median sCD163 levels were decreased for HIV-1-infected patients (P < 0.001), but not among HIV-2 (P = 0.093) or HIV-1/2 dually infected patients (P = 0.145). The larger decrease in sCD163 levels among HIV-1-infected patients during ART may indicate an HIV type dependent differential effect of ART on macrophage activation during HIV infection. PMID- 26825180 TI - Spinal Cord Injury Caused by Stab Wounds: Incidence, Natural History, and Relevance for Future Research. AB - Spinal cord injury caused by stab wounds (SCISW) results from a partial or complete transection of the cord, and presents opportunities for interventional research. It is recognized that there is low incidence, but little is known about the natural history or the patient's suitability for long-term clinical outcome studies. This study aims to provide population-based evidence of the demographics of SCISW, and highlight the issues regarding the potential for future research. The database of the Queen Elizabeth National Spinal Injuries Unit (QENSIU), the sole center for treating SCI in Scotland, was reviewed between 1994 and 2013 to ascertain the incidence, demographics, functional recovery, and mortality rates for new SCISW. During this 20 year period, 35 patients with SCISW were admitted (97.1% male, mean age 30.0 years); 31.4% had a cervical injury, 60.0% had a thoracic injury, and 8.6% had a lumbar injury. All had a neurological examination, with 42.9% diagnosed as motor complete on admission and 77.1% discharged as motor incomplete. A total of 70.4% of patients with an American Spinal Injury Association Impairment Scale (AIS) level of A to C on admission had an improved AIS level on discharge. Nine (25.7%) patients have died since discharge, with mean life expectancy for these patients being 9.1 years after injury (20-65 years of age). Patients had higher levels of comorbidities, substance abuse, secondary events, and poor compliance compared with the general SCI population, which may have contributed to the high mortality rate observed post-discharge. The low incidence, heterogeneous nature, spontaneous recovery rate, and problematic follow-up makes those with penetrating stab injuries of the spinal cord a challenging patient group for SCI research. PMID- 26825181 TI - Letter from the guest editors: Cell adhesion, migration, and fusion in placenta. PMID- 26825182 TI - Pregnancy-associated severe sepsis. AB - PURPOSE OF REVIEW: This article examines the contemporary knowledge and uncertainties about the burden of pregnancy-associated severe sepsis (PASS), and its manifestations, management, and outcomes. RECENT FINDINGS: There are relatively sparse data on PASS, related in part to infrequent reports and varying use of terminology and case definitions. PASS remains rare, although its incidence appears to be rapidly rising in some high-resource countries, affecting especially women with limited resources, minorities, and those with chronic illness. High level of clinician vigilance and rapid initiation of appropriate antimicrobial therapy, coupled with effective systemic support for organ dysfunction and correction of occult and overt hypoperfusion are the keys to limit adverse outcomes. However, timely diagnosis and provision of effective care remain a challenge, with reported prevalent delay in recognition and delivery of time-sensitive care interventions among maternal decedents. The mortality rate of PASS has been rising and its case fatality, although relatively low, has remained unchanged, in contrast to the outcome gains in the general population. The long term sequelae of PASS remain unknown. SUMMARY: The relatively limited contemporary data on PASS suggest a rising public health hazard in the obstetric population in high-resource countries, with ongoing challenges in assuring consistent provision of time-sensitive care. PMID- 26825179 TI - Brief Report: Intestinal Microbiota-Produced Trimethylamine-N-Oxide and Its Association With Coronary Stenosis and HIV Serostatus. AB - Recent evidence has shown a complex relationship between the gut microbiota, dietary nutrients, and cardiovascular disease (CVD). Trimethylamine-N-oxide (TMAO) production, initiated by the microbiota, has been associated with CVD events. We sought to test if this association exists in HIV-infected persons. After adjusting for aspirin use and CVD risk factors, HIV-infected men were more likely to have coronary stenosis in the second and third TMAO quartiles compared with the first quartile, but did not differ significantly in the fourth quartile. We found an inverted U-shaped association between TMAO levels and the presence of coronary artery stenosis among HIV-infected men. PMID- 26825183 TI - Placental examination: prognosis after delivery of the growth-restricted fetus. AB - PURPOSE OF REVIEW: This article describes the role of placental examination in the prognostic evaluation of fetal growth restriction (FGR) infants. RECENT FINDINGS: A new comprehensive placental classification system was reported. Maternal underperfusion, fetal thrombotic vasculopathy (FTV), villitis (including villitis of unknown etiology and infectious villitis), inflammation, and immature/dysmature villi are important factors affecting FGR prognosis, whereas genomic imprinting is a key factor affecting growth and diseases, as well as placental abnormality. SUMMARY: We discuss the role of placental examination in determining FGR prognosis. Maternal underperfusion, fetal thrombotic vasculopathy, and villitis (including villitis of unknown etiology and infectious villitis) are the most important findings affecting FGR prognosis. Although limited, data have suggested an association of inflammation and immature/dysmature villi with postnatal growth in FGR infants. Placental size also contributes postnatally through fetal programming. In addition, placental imprinting can be a key of pre and postnatal growth and diseases, including imprinting disorders, as well as placental abnormalities such as placental mesenchymal dysplasia. PMID- 26825185 TI - Editorial: The New Decade. PMID- 26825184 TI - Guest Editorial: Toward Broader Applications of Multivariate Methods. PMID- 26825186 TI - MAXIMUM VARIANCE LINEAR COMBINATIONS FROM PHENOTYPIC, GENETIC, AND ENVIRONMENTAL COVARIANCE MATRICES. AB - Vectors of weights derived from principal components analysis of stan- dardized phenotypic, genetic, and environmental covariance matrices were applied to open field behavioral scores from mice in order to obtain composite scores with maximum phenotypic (Vp), genetic (Va), and environmental (Ve)variance, respectively. Since Va associated with the composite from the genetic covariance matrix is derived as maximum, and since Vp associated with this combination cannot be as large as that associated with the phenotypic com- posite, heritability of the genetic composite must exceed that of the phenotypic composite. In addition, since Ve associated with the environmental composite is maximum and since Vp associated with this score cannot exceed Vp from the phenotypic composite, Va associated with the phenotypic composite should exceed that from the environmental composite. Thus, heritability of the pheno- typic composite scores should exceed that for the environmental composite. The predicted rank order of the heritabilities was observed. Pooled estimates of the heritabilities of the genetic, phenotypic, and environmental components were 0.24, 0.19, and 0.17, respectively. PMID- 26825187 TI - FACTOR ANALYSIS OF EMOTIONALITY IN TEN INBRED STRAINS OF MICE. AB - One hundred and nineteen mice of 10 inbred strains were run on 32 measures from 16 tests in order to obtain a large variance coverage of behavioral differences for the purpose of obtaining factors among emotionality measures and strain factor scores. PMID- 26825189 TI - THE PROJECTION OF COLLEGE ENROLLMENT. AB - This study investigates the problem of predicting future college enrollment in one course, in a group of courses combined, or in a whole college or system. Several methods that utilize the techniques of other multiple regression analysis are suggested. Assumed models include deterministic models with simple random component, stochastic models, and models containing both deterministic and stochastic components. PMID- 26825188 TI - THE CHILD BEHAVIOR CHARACTERISTICS (CBC) FORM: REVISED AGE-SPECIFIC FORMS. AB - The rationale and problems in the development of age-specific CBC forms are described. The relevance of concepts to specific ages and the amount of contact required for rating are precursors t o development of rating forms. Clusters of items that have relevance for the earliest ages were derived from a sequence of studies. The consistency of these clusters in older ages, and the relationship of these to clusters applicable only to the older ages is noted. Reliability and between-cluster correlations are presented. PMID- 26825190 TI - A METHOD OF CLUSTER ANALYSIS. AB - Different applicatiions require different systems of cluster analysis. The ways in which systems differ are pointed out. The present system was designed originally; to identify, in a homogeneous callection of questionnaire or inventory items or of tests, groups of items which can be scored as subtests, or groups of tests which can be combined to yield globa1-trait scores, but it may well be applicable to other problems. PMID- 26825191 TI - A NOTE ON THE EFFECT OF SELECTIVE SAMPLING PROCEDURES ON THE PHI COEFFICIENT. AB - A general equadion is presented, covering all arbitrary values for the true population splits, for obtaining the true population phi, given observed cell frequencies for a selected sample, and true population splits. A nongeneral solution is also offered, based on the use of the G Index. Demonstrations with hypothetical data are given. PMID- 26825192 TI - CODIMENSIONALITY WITHOUT HIGH CORRELATION. AB - The product moment correlation of discrete variables is depressed by differences in the variables' distributions which are consistent with their variables are actually codimensional and so to bias convergent validation studies toward rejectring a true hypothesis of (sufficient) convergence. 3 being codimensional. This makes it prone to indicate multidimensionality when variables are actually codimensional and so to bias convergent validation studies toward rejectring a true hypothesis of (sufficient) convergence. PMID- 26825193 TI - Integrative medicine: A primer. PMID- 26825194 TI - Random musings on a Sunday afternoon. PMID- 26825195 TI - 18F-Choline PET/CT-Positive Lytic Bone Lesions in Prostate Cancer and Accidental Myeloma Detection. AB - F-choline PET/CT was performed for suspected prostate cancer relapse in a 67-year old man with hip pain and a rapid rise in prostate-specific antigen values (1.1 ng/mL). PET imaging showed an area of increased F-choline bone uptake in the right ischium. Coregistered CT images showed a lytic bone lesion. The infrequent CT appearance of a possible prostate carcinoma metastasis led to additional laboratory testing that showed a monoclonal gamma-peak and to subsequent biopsy, which revealed a solitary plasmocytoma. PMID- 26825196 TI - Abnormal FDG and MIBG Activity in the Bones in a Patient With Neuroblastoma Without Detectable Primary Tumor. AB - Neuroblastoma is among the most common extracranial solid tumors in pediatric patients and typically arises anywhere from the neck to pelvis but most commonly in the adrenal glands. It is extremely rare for a patient to have extensive metastases from neuroblastoma without primary tumor being identified. We present a 3-year-old with widespread bone and bone marrow involvement of the disease revealed on both FDG PET/CT and MIBG scan, which was pathologically proven as neuroblastoma. However, extensive imaging did not detect primary tumor anywhere. PMID- 26825197 TI - A Mimic of Intra-abdominal Malignancy: Physiological Urinary Excretion of FDG in the Rare Adult Vesicourachal Diverticulum. AB - Urachal remnant anomalies are rare, and vesicourachal diverticulum is the most uncommon subtype of these anomalies. We present such a rare case of vesicourachal diverticulum that is incidentally discovered during the staging surveillance of a known esophageal cancer with F-FDG PET/CT. The physiological urinary excretion of radiopharmaceutical in the vesicourachal diverticulum mimics intra-abdominal malignancy, which resolves spontaneously in the follow-up FDG PET/CT. PMID- 26825198 TI - Renal Cell Carcinoma Arising From Renal Allograft Detected by 18F-FDG PET-CT. AB - Renal cell carcinoma arising from renal allograft is a rare condition. A 56-year old man with a history of 3 renal transplantation due to renal failure presented poor appetite and weight loss for 3 months. Possibility of tumor of unknown origin was suspected. For this reason, an FDG PET/CT was performed, and the images showed a hypermetabolic focus in the lower pole of the left renal transplant, suggestive of a malignant lesion. Subsequent pathological examination following allograft nephrectomy confirmed grade 4 renal cell carcinoma. PMID- 26825199 TI - Re: Lymphatic Path of the Inguinal Lymph Node Metastases in Anorectal Cancer: The Springbok Pattern. PMID- 26825200 TI - Facial Paralysis Secondary to Extensive Perineural Spread of Adenocarcinoma of the Parotid Gland Identified by PET/CT. AB - Brain MRI in an 82-year-old man with presumed Bell's palsy revealed a clinically unsuspected right parotid gland mass but no other acute findings. Biopsy revealed poorly differentiated adenocarcinoma. Staging F-FDG PET/CT revealed an FDG-avid parotid mass, abnormal FDG uptake along the course of the facial nerve from mass to skull base, and multiple FDG-avid right level II neck lymph nodes and hepatic metastases. The PET/CT findings and prolonged clinical course suggest that diffuse perineural spread of tumor from a smoldering parotid neoplasm, and not idiopathic Bell's palsy, was responsible for the patient's facial paralysis. PMID- 26825201 TI - Lack of Increased FDG Uptake in the Lacrimal and Salivary Glands in Patients With Sarcoidosis and Potential Underlying Mechanism. AB - PURPOSE: Increased 67Ga uptake in the mediastinal/hilar lymph nodes ("lambda") and in the lacrimal/parotid/submandibular glands ("panda") often coexists in patients with sarcoidosis (Sarc-Pts). However, we observed that increased lacrimal/salivary uptake is uncommon on 18F-FDG PET/CT (FDG-panda) in many Sarc Pts who showed increased mediastinal/hilar uptake (FDG-lambda). We evaluated parotid and lacrimal FDG activity in Sarc-Pts who showed FDG-lambda in comparison with a control patient group and attempted to find underlying mechanisms to explain the discrepancy between FDG and Ga uptake in these organs. METHODS: Parotid FDG activity (FDG-P) was assessed visually using a 0- to 3-point scale (0 being = or minimally > background, and 3 > liver) and quantitatively using SUVmean in 52 confirmed Sarc-Pts with FDG-lambda (lambda group) as well as in 52 non-Sarc-Pts (control group). Lacrimal FDG activity (FDG-L) was assessed visually (0 being = or minimally > subcutaneous tissue, and 1 clearly > subcutaneous tissue). RESULTS: There was no significant difference in the parotid SUVmean between lambda (1.88 +/- 0.65) and control (1.76 +/- 0.62) groups (P = 0.333). Also, there was no difference in visually graded FDG-P between the 2 groups (P = 0.257). None of the patients in all groups showed apparently abnormal (grade 1) FDG-L. CONCLUSIONS: Increased FDG-L/FDG-P is rare in Sarc-Pts demonstrating FDG lambda, which is strikingly different from the clinical experience as well as the reported data on Ga scintigraphy. Discrepancy in various cytokine levels between lacrimal samples and intrathoracic lesions in Sarc-Pts reported in the literature appears to correlate well with variable Ga and FDG uptake in the lacrimal gland and intrathoracic lesions. PMID- 26825202 TI - FDG PET/CT Findings of Menetrier Disease. AB - Menetrier disease is a very rare chronic gastric disorder characterized by gastric mucosal hypertrophy. We present a case of Menetrier disease with CT, MRI, and FDG PET/CT findings. Enhanced CT and MRI showed diffuse thickened mucosa of the greater curvature and elongated mucosa of the antrum with remarkable enhancement. The early and delayed FDG PET/CT showed increased FDG uptake of these thickened mucosa. The increased FDG uptake may be due to the mucosal inflammation. This case indicates Menetrier disease should be included in the differential diagnosis of abnormal gastric FDG accumulation along with tumor and nontumor processes. PMID- 26825203 TI - Increased 18F-FDG Uptake Associated With Gastric Banding Surgical Mesh on PET/CT. AB - Surgical mesh was used in the 1980s and early 1990s for vertical banded gastroplasty as treatment for morbid obesity. This procedure was replaced by the more popular laparoscopic gastric banding in the mid-1990s. Surgical mesh, commonly used in hernioplasty, has been associated with increased F-FDG uptake related to an inflammatory foreign body reaction and is a known cause of false positive PET scans. We present a case of increased F-FDG uptake related to surgical mesh in a patient who had undergone vertical banded gastroplasty. PMID- 26825204 TI - Prognostic Value of Volumetric Parameters on Staging and Posttreatment FDG PET/CT in Patients With Stage IV Non-Small Cell Lung Cancer. AB - PURPOSE: This study aimed to evaluate the prognostic value of metabolic tumor burden as measured with metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as well as SUVmax on initial staging and posttreatment F-FDG PET/CT in patients with stage IV non-small cell lung cancer (NSCLC). METHODS: Sixty-three NSCLC patients with stage IV who underwent staging and posttreatment FDG PET/CT after completion of the first-line chemotherapy were retrospectively enrolled. SUVmax, MTV, and TLG of primary cancer and all metastatic lesions (lymph node and distant metastases) on both PET/CT images were measured and their association with progression-free survival (PFS) and overall survival (OS) analyzed. RESULTS: Median PFS and OS in the patient population were 5.9 and 23.1 months, respectively. Among the PET/CT parameters, MTV and TLG of primary cancer lesions on initial PET/CT and MTV and TLG of metastatic lesions on posttreatment PET/CT were independent prognostic factors for both PFS and OS (P < 0.05). The median OS in patients who showed low values of those PET/CT parameters was more than 26.0 months, whereas patients with high values of those parameters had a median OS of less than 15.0 months. CONCLUSIONS: Metabolic tumor burdens of primary cancer lesions on staging PET/CT and metastatic lesions on posttreatment PET/CT were independent prognostic factors in patients with stage IV NSCLC. Volume-based PET parameters could further stratify the prognosis of stage IV NSCLC patients. PMID- 26825205 TI - Choroidal Metastasis of Papillary Thyroid Carcinoma Demonstrated on SPECT-CT. AB - We report a 68-year-old woman with papillary thyroid carcinoma metastasizing to choroid. The choroid metastasis was diagnosed with SPECT-CT and then was treated with high-dose radioactive iodine therapy. PMID- 26825206 TI - Reversible Changes of Brain Perfusion SPECT for Carbon Monoxide Poisoning-Induced Severe Akinetic Mutism. AB - PURPOSE: This study aimed to characterize changes in regional cerebral blood flow (rCBF) in patients who experienced carbon monoxide (CO) poisoning and subsequently developed severe delayed neuropsychiatric sequelae (DNS) with akinetic mutism. We determined whether these changes were reversible in parallel with improvements in neuropsychological function in response to treatment, including hyperbaric oxygen therapy. METHODS: Patients who developed severe DNS with akinetic mutism after acute CO intoxication between 2007 and 2011 were enrolled. Tc-ECD brain SPECT findings were compared between the patients with severe akinetic mutism and age-matched control subjects to characterize the pattern of rCBF. Perfusion SPECT was correlated with clinical outcomes after treatment with statistical parametric mapping (SPM8); the height threshold was P < 0.01 at peak level, and the corrected false discovery rate was P < 0.05 at the cluster level. RESULTS: Seven patients with akinetic mutism were analyzed. All patients had neurological symptoms caused by acute CO exposure, and all recovered to nearly normal daily function after initial treatments. In all cases, after a "lucid interval," DNS progressed to akinetic mutism. The SPECT images acquired at the onset of akinetic mutism demonstrated variable hypoperfusion in frontal temporal-parietal regions, with the greatest severity in the left temporal parietal regions. In parallel, we performed functional neuropsychiatric tests. After treatment, the brain SPECT showed significantly fewer hypoperfusion regions, and neuropsychiatric tests showed dramatically improved function. CONCLUSIONS: Our findings demonstrated both cerebral cortical and subcortical injuries in patients with CO-induced akinetic mutism. Improvement in rCBF correlated well with functional recovery after treatment. PMID- 26825207 TI - 18F-FDG PET/CT in Detecting Metastatic Infection in Children. AB - PURPOSE OF THE REPORT: Metastatic infection is a severe complication of bacteremia with high morbidity and mortality. The aim of this study was to investigate the diagnostic value of 18F-FDG PET combined with CT (FDG PET/CT) in children suspected of having metastatic infection. METHODS: The results of FDG PET/CT scans performed in children because of suspected metastatic infection from September 2003 to June 2013 were analyzed retrospectively. The results were compared with the final clinical diagnosis. RESULTS: FDG PET/CT was performed in 13 children with suspected metastatic infection. Of the total number of FDG PET/CT scans, 38% were clinically helpful. Positive predictive value of FDG PET/CT was 71%, and negative predictive value was 100%. CONCLUSIONS: FDG PET/CT appears to be a valuable diagnostic technique in children with suspected metastatic infection. Prospective studies of FDG PET/CT as part of a structured diagnostic protocol are needed to assess the exact additional diagnostic value. PMID- 26825208 TI - Focal Hepatic Hot Spot From Superior Vena Cava Occlusion Visualized on Ventilation/Perfusion Scintigraphy With Contrast-Enhanced CT Correlate. AB - A 57-year-old woman with superior vena cava stenosis from repeated central line placements underwent ventilation/perfusion scanning after presenting with pleuritic chest pain. The ventilation/perfusion scan was not characteristic for pulmonary embolus, but perfusion images demonstrated abnormal radiotracer activity within hepatic segment 4, along with extensive collateral vessels as seen on SPECT/CT. Two months later, the patient presented with similar complaints and had a chest CT with contrast to evaluate for pulmonary embolus. This showed occlusion of the superior vena cava and arterial enhancement within segment 4 in a similar distribution to the radiotracer in the perfusion scan. PMID- 26825209 TI - Influence of Multigland Parathyroid Disease on 99mTc-Sestamibi SPECT/CT. AB - PURPOSE: 99mcTc-sestamibi (MIBI) imaging is performed for preoperative parathyroid lesion localization in patients with primary hyperparathyroidism. Decreased sensitivity in multigland disease (MGD) compared with single-gland disease (SGD) is well recognized for planar and SPECT imaging, but few data are available on MIBI SPECT/CT in MGD. METHODS: We retrospectively analyzed 246 patients with primary hyperparathyroidism who underwent preoperative MIBI SPECT/CT. Surgical and pathology reports were used to confirm numbers, weights, and locations of excised glands. Two experienced physicians independently read MIBI SPECT/CTs, grading lesion certainty on a 5-point scale ("definitely normal" to "definitely abnormal"). RESULTS: Three hundred one parathyroid lesions were excised at surgery. Thirty-nine patients (16%) had MGD, and 207 patients (84%) had SGD; 26 patients had 2 lesions, 10 had 3 lesions, and 3 had 4 lesions. Lesion weights were significantly lower in MGD than in SGD (390 +/- 604 vs 866 +/- 933 mg, P < 0.0001) and decreased with increasing numbers of lesions (P < 0.0001). MIBI SPECT/CT was less sensitive for MGD than SGD (66% vs 98%, P < 0.0001). Sensitivity was lower for 66 MGD lesions matched to 66 SGD lesions (64% vs 98%, P < 0.0001) and decreased with increasing lesion numbers (rho = -0.45, P < 0.0001), despite similar weights (526 +/- 678 vs 525 +/- 686 mg, P = 0.99) and similar locations (P = 0.47). Specificity was similar for MGD (95%) and SGD (90%). CONCLUSIONS: 99mcTc-MIBI SPECT/CT sensitivity is significantly lower in MGD than in SGD. This does not appear to be related to lesion weight or location. PMID- 26825210 TI - Absolute Quantitative Evaluation of 67Ga Scintigraphy in Lupus Nephritis. AB - PURPOSE: Renal biopsy is crucial for management of lupus nephritis. However, it is invasive and can cause bleeding and infection. In our previous study, we developed a semiquantitative method for gallium renal imaging and demonstrated a good correlation between the left kidney-to-spine ratio (K/S ratio) and the results of renal biopsy. However, the accuracy of left K/S ratio is compromised by the variation of spinal gallium uptake, especially in patients with extraordinarily high or low gallium uptakes in the spine. In this study, we developed an absolute quantitative method and compared the results of quantitative gallium images, semiquantitative gallium images, visual methods, and renal biopsies. METHODS: Thirty-four patients with lupus nephritis were enrolled and underwent renal biopsy to determine activity index (AI) and chronicity index. A delayed 48-hour gallium scan was also performed and interpreted by visual, semiquantitative, and absolute quantitative methods. For absolute quantitative analysis, a standard solution with activities of approximately 555 KBq (15 MUCi) was prepared and poured into a 5-mL tube, which was placed close to the patient. ROIs were drawn around the outer edge of the left kidney as well as around the outer edges of the standard. A kidney uptake index (KUI) was calculated, and the results were compared with K/S ratio, visual grading, and renal biopsies. RESULTS: Kidney uptake index had the best correlation with AI among the 3 methods using Spearman rank correlation test. The Spearman R values were 0.78, 0.71, and 0.61 for KUI, K/S ratio and visual grading, respectively. Chronicity index did not correlate well with the results of any of the 3 methods. In addition, AI was significantly higher in patients with a KUI equal to or greater than 1.5, when compared with patients with a KUI lower than 1.5 (P = 0.00001 by Mann-Whitney U test). Using a K/S ratio of 0.95 as a cutoff value, AI also showed a statistically significant difference with P = 0.0001. When a visual grading of 2 was used as a cutoff value, P = 0.0008. The difference in AI was most significant when the statistical value was based on the KUI. CONCLUSIONS: The KUI showed better correlation with the results of renal biopsy than the K/S ratio and the visual grading. We suggest that the KUI from the absolute quantitative renal gallium scintigraphy may be a useful parameter for evaluating the disease activity in lupus nephritis. PMID- 26825211 TI - Increased 18F-FDG Uptake in the Spleen and Multiple Lymph Nodes in Dengue Fever. AB - A 62-year-old man underwent a whole-body FDG PET/CT for annual cancer screening. By an interview, he had an epigastric pain, and his body temperature was 37.0 degrees C on the day. He just came back home from a travel to Southeast Asia 1 week ago and had presented with chill, high fever (temperature, 39.6 degrees C), arthralgia, myalgia, and skin rash a few days before. Dengue fever was diagnosed by detecting dengue virus type 1 genome and antibody to the virus accompanied by thrombocytopenia and leukopenia. PET/CT examination revealed increased FDG uptake in the spleen and multiple lymph nodes. PMID- 26825212 TI - Molecular Imaging in the Management of Adrenocortical Cancer: A Systematic Review. AB - Adrenocortical cancer (ACC) is an uncommon primary neoplasm of the adrenal cortex with dismal prognosis. It often presents with symptoms and signs of adrenal cortical hormone hypersecretion and abdominal mass effect or is incidentally detected as an adrenal mass on imaging performed for other indications. Endocrine evaluation, comprehensive staging, and meticulous resection are crucial to ensure the best possible outcome. Despite extensive initial surgical resection, local and distant metastases are not uncommon with disappointing 5-year survival, although progress is being made at high-volume centers. Accurate restaging of recurrent disease is important to guide further management. Mitotane, external beam radiation and chemotherapy, and newer anticancer systemic treatments are used as adjunctives for inoperable disease and distant metastases. Contrast enhanced CT and MRI are first-line imaging modalities for evaluation of ACC to characterize adrenal masses and to determine tumor resectability. Emerging literature supports F-FDG PET/CT use to determine the malignant potential of adrenal masses. In patients with a diagnosis of ACC, FDG PET/CT is sensitive for detecting metastatic disease, and its tumor accumulation has been correlated to pathology, Weiss scores, and prognosis. Metomidate, labeled with C for PET or with I for SPECT/CT, allows characterization of an adrenal mass as being of adrenocortical origin with high specificity. Taking advantage of its adrenocortical avidity, metomidate has been labeled with I for radionuclide therapy in a subset of ACC. In this review, we describe how nuclear medicine imaging, and specifically PET, can assist surgical management of ACC. PMID- 26825213 TI - FDG PET/CT Findings in Abdominal Fat Necrosis After Treatment for Lymphoma. AB - FDG PET/CT is now validated in non-Hodgkin lymphoma for response assessment in interim and posttreatment lymphoma. We report the case of a 62-year-old man followed by FDG PET/CT for a diffuse large B-cell lymphoma, with initial stage III. The interim FDG PET/CT examination concluded in complete metabolic and morphological response of subdiaphragmatic lymphadenopathy but a persistent abnormal subdiaphragmatic uptake (SUVmax at 9 and Deauville 5-point scale at 5). Therefore, an abdominal biopsy of the corresponding nodules was conducted with a final diagnosis of diffuse fat necrosis. PMID- 26825214 TI - Burkitt Lymphoma Presented as Acute Lower Back Pain and Revealed by 18F-NaF PET/CT. AB - A 15-year-old man with acute lower back pain for 7 days underwent F-NaF PET/CT to determine the cause of his symptoms. The PET images revealed irregularly increased F activity in the L1 vertebral body without definite sclerotic changes on CT. However, the corresponding CT images revealed an adjacent paravertebral mass extending into the vertebral foramen without elevated activity on PET. A diagnosis of Burkitt lymphoma was made after pathological examination. PMID- 26825215 TI - Lymphatic Path of the Inguinal Lymph Node Metastases in Anorectal Cancer: The Springbok Pattern: Reply. PMID- 26825216 TI - Probing the Electronic Structure and Chemical Bonding of Mono-Uranium Oxides with Different Oxidation States: UOx(-) and UOx (x = 3-5). AB - Uranium oxide clusters UOx(-) (x = 3-5) were produced by laser vaporization and characterized by photoelectron spectroscopy and quantum theory. Photoelectron spectra were obtained for UOx(-) at various photon energies with well-resolved detachment transitions and vibrational resolution for x = 3 and 4. The electron affinities of UOx were measured as 1.12, 3.60, and 4.02 eV for x = 3, 4, and 5, respectively. The geometric and electronic structures of both the anions and the corresponding neutrals were investigated by quasi-relativistic electron correlation quantum theory to interpret the photoelectron spectra and to provide insight into their chemical bonding. For UOx clusters with x <= 3, the O atoms appear as divalent closed-shell anions around the U atom, which is in various oxidation states from U(II)(fds)(4) in UO to U(VI)(fds)(0) in UO3. For x > 3, there are no longer sufficient valence electrons from the U atom to fill the O(2p) shell, resulting in fractionally charged and multicenter delocalized valence states for the O ligands as well as eta(1)- or eta(2)-bonded O2 units, with unusual spin couplings and complicated electron correlations in the unfilled poly oxo shell. The present work expands our understanding of both the bonding capacities of actinide elements with extended spdf valence shells as well as the multitude of oxygen's charge and bonding states. PMID- 26825217 TI - Colectomy rates in patients with ulcerative colitis following treatment with infliximab or ciclosporin: a systematic literature review. AB - This review aimed to compile all available published data on colectomy rates following treatment using infliximab or ciclosporin in adult ulcerative colitis patients and to analyse colectomy rates, timing to colectomy and postcolectomy mortality for each treatment. We systematically reviewed the literature after 1990 reporting colectomy rates in ulcerative colitis patients treated with infliximab or ciclosporin, excluding articles on paediatric patients, patients with indeterminate colitis or Crohn's disease and bowel surgery not related to ulcerative colitis. We presented weighted mean colectomy rates and mortality rates. Cox's regression was used to assess time to colectomy adjusting for colitis severity, patient age and sex. We tabulated 78 studies reporting on ciclosporin and/or infliximab and colectomy rates or postcolectomy mortality rates. Not all studies reported data in a standardized manner. Infliximab had a significantly lower colectomy rate than ciclosporin at 36 months when analysing all studies, studies directly comparing infliximab and ciclosporin and studies using severe colitis patients, but not at 3, 12 or 24 months. Severity and age were key indicators in the likelihood of undergoing colectomy after treatment. Postcolectomy mortality rates were less than 1.5% for both drugs. This review indicates that long-term colectomy rates following infliximab are significantly lower than ciclosporin in the longer term, and that postcolectomy mortality following infliximab and ciclosporin is very low. However, many key data items were missing from research articles, reducing our ability to establish with more confidence the actual impact of these two drugs on colectomy rates and postcolectomy mortality rates. PMID- 26825218 TI - Vitamin D deficiency in paediatric intensive care units: a global problem and shared opportunity. PMID- 26825223 TI - Delay and misdiagnosis of basidiobolomycosis in tropical South India: case series and review of the literature. AB - Basidiobolomycosis caused by Basidiobolus ranarum is a rare infection of the subcutaneous tissues in immune-competent patients which occurs predominantly in children and young adults. Primary physicians often misdiagnose the condition owing to its slow, painless, relentless growth, absence of response to antibiotics and anti-inflammatory drugs and unfamiliarity with this lesion. All cases of subcutaneous basidiobolomycosis in children aged between 1 and 12 years presenting at a tertiary hospital in Pondicherry over a period of 4 years (2007 2011) were analysed. Eight cases were seen and confirmed by histopathology and microbiology. Referral diagnoses varied widely from chronic abscess to tuberculosis to malignancy, including testicular tumour. Lesion sites include the gluteal region, thigh and scrotum (extremely rare). Four weeks of oral itraconazole in seven children and fluconazole (5 mg/kg) in one cured them completely. During follow-up for over 1 year, no recurrence or new lesions were noted. Basidiobolomycosis is a rare, often misdiagnosed infection in children which responds well to triazole antifungals such as itraconazole and fluconazole. PMID- 26825226 TI - Is the late hypersensitivity reaction in nephritic syndrome following multiple bee stings dosedependent? PMID- 26825228 TI - E2f4 and E2f5 are essential for the development of the male reproductive system. AB - The E2F transcription factors are primarily implicated in the regulation of entry and exit from the cell cycle. However, in vivo studies have established additional roles for E2Fs during organ development and homeostasis. With the goal of addressing the intestinal requirements of E2f4 and E2f5, we crossed mice carrying Vil-cre, E2f4 conditional and E2f5 germline alleles. E2f4 deletion had no detectable effect on intestinal development. However, E2f4f/f;E2f5+/-;Vil-cre males, but not E2f4f/f;Vil-cre littermates, were unexpectedly sterile. This defect was not due to defective spermatogenesis. Instead, the seminiferous tubules and rete testes showed significant dilation, and spermatozoa accumulated aberrantly in the rete testis and efferent ducts. Our data show that these problems result from defective efferent ducts, a tissue whose primary function is to concentrate sperm through fluid absorption. First, Vil-cre expression, and consequent E2F4 loss, was specific to the efferent ducts and not other reproductive tract tissues. Second, the E2f4f/f;E2f5+/-;Vil-cre efferent ducts had completely lost multiciliated cells and greatly reduced levels of critical absorptive cell proteins: aquaporin1, a water channel protein, and clusterin, an endocytic marker. Collectively, the observed testis phenotypes suggest a fluid flux defect. Remarkably, we observed rete testis dilation prior to the normal time of seminiferous fluid production, arguing that the efferent duct defects promote excessive secretory activity within the reproductive tract. Finally, we also detect key aspects of these testis defects in E2f5-/- mice. Thus, we conclude that E2f4 and E2f5 display overlapping roles in controlling the normal development of the male reproductive system. PMID- 26825227 TI - Coordinating cell proliferation and differentiation: Antagonism between cell cycle regulators and cell type-specific gene expression. AB - Cell proliferation and differentiation show a remarkable inverse relationship. Precursor cells continue division before acquiring a fully differentiated state, while terminal differentiation usually coincides with proliferation arrest and permanent exit from the division cycle. Mechanistic insight in the temporal coordination between cell cycle exit and differentiation has come from studies of cells in culture and genetic animal models. As initially described for skeletal muscle differentiation, temporal coordination involves mutual antagonism between cyclin-dependent kinases that promote cell cycle entry and transcription factors that induce tissue-specific gene expression. Recent insights highlight the contribution of chromatin-regulating complexes that act in conjunction with the transcription factors and determine their activity. In particular SWI/SNF chromatin remodelers contribute to dual regulation of cell cycle and tissue specific gene expression during terminal differentiation. We review the concerted regulation of the cell cycle and cell type-specific transcription, and discuss common mutations in human cancer that emphasize the clinical importance of proliferation versus differentiation control. PMID- 26825229 TI - Two different specific JNK activators are required to trigger apoptosis or compensatory proliferation in response to Rbf1 in Drosophila. AB - The Jun Kinase (JNK) signaling pathway responds to diverse stimuli by appropriate and specific cellular responses such as apoptosis, differentiation or proliferation. The mechanisms that mediate this specificity remain largely unknown. The core of this signaling pathway, composed of a JNK protein and a JNK kinase (JNKK), can be activated by various putative JNKK kinases (JNKKK) which are themselves downstream of different adaptor proteins. A proposed hypothesis is that the JNK pathway specific response lies in the combination of a JNKKK and an adaptor protein upstream of the JNKK. We previously showed that the Drosophila homolog of pRb (Rbf1) and a mutant form of Rbf1 (Rbf1(D253A)) have JNK-dependent pro-apoptotic properties. Rbf1(D253A) is also able to induce a JNK-dependent abnormal proliferation. Here, we show that Rbf1-induced apoptosis triggers proliferation which depends on the JNK pathway activation. Taking advantage of these phenotypes, we investigated the JNK signaling involved in either Rbf1 induced apoptosis or in proliferation in response to Rbf1-induced apoptosis. We demonstrated that 2 different JNK pathways involving different adaptor proteins and kinases are involved in Rbf1-apoptosis (i.e. Rac1-dTak1-dMekk1-JNK pathway) and in proliferation in response to Rbf1-induced apoptosis (i.e., dTRAF1-Slipper JNK pathway). Using a transient induction of rbf1, we show that Rbf1-induced apoptosis activates a compensatory proliferation mechanism which also depends on Slipper and dTRAF1. Thus, these 2 proteins seem to be key players of compensatory proliferation in Drosophila. PMID- 26825231 TI - 1-year outcomes with the Absorb bioresorbable scaffold in patients with coronary artery disease: a patient-level, pooled meta-analysis. AB - BACKGROUND: Compared with metallic drug-eluting stents, bioresorbable vascular scaffolds (BVS) offer the potential to improve long-term outcomes of percutaneous coronary intervention. Whether or not these devices are as safe and effective as drug-eluting stents within the first year after implantation is unknown. METHODS: We did a patient-level, pooled meta-analysis of four randomised trials in which 3389 patients with stable coronary artery disease or a stabilised acute coronary syndrome were enrolled at 301 academic and medical centres in North America, Europe, and the Asia-Pacific region. These patients were randomly assigned to the everolimus-eluting Absorb BVS (n=2164) or the Xience cobalt-chromium everolimus eluting stent (CoCr-EES; n=1225). The primary endpoints were the 1-year relative rates of the patient-oriented composite endpoint (all-cause mortality, all myocardial infarction, or all revascularisation) and the device-oriented composite endpoint of target lesion failure (cardiac mortality, target vessel related myocardial infarction, or ischaemia-driven target lesion revascularisation). All analyses were by intention to treat. The four randomised trials included in our meta-analysis are all registered with ClinicalTrials.gov, numbers NCT01751906, NCT01844284, NCT01923740, and NCT01425281. FINDINGS: The summary treatment effect for the 1-year relative rates of the patient-oriented composite endpoint did not differ significantly different between BVS and CoCr EES (relative risk [RR] 1.09 [0.89-1.34], p=0.38). Similarly, the 1-year relative rates of the device-oriented composite endpoint did not differ between the groups (RR 1.22 [95% CI 0.91-1.64], p=0.17). Target vessel-related myocardial infarction was increased with BVS compared with CoCr-EES (RR 1.45 [95% CI 1.02-2.07], p=0.04), due in part to non-significant increases in peri-procedural myocardial infarction and device thrombosis with BVS (RR 2.09 [0.92-4.75], p=0.08). The relative rates of all-cause and cardiac mortality, all myocardial infarction, ischaemia-driven target lesion revascularisation, and all revascularisation did not differ between BVS and CoCr-EES. Results were similar after multivariable adjustment for baseline imbalances, and were consistent across most subgroups and in sensitivity analysis when two additional randomised trials with less than 1 year of follow-up were included. INTERPRETATION: In this meta-analysis, BVS did not lead to different rates of composite patient-oriented and device-oriented adverse events at 1-year follow-up compared with CoCr-EES. FUNDING: Abbott Vascular. PMID- 26825232 TI - Insulin patents and market exclusivities: unresolved issues--Authors' reply. PMID- 26825230 TI - Translational regulation of the mRNA encoding the ubiquitin peptidase USP1 involved in the DNA damage response as a determinant of Cisplatin resistance. AB - Cisplatin (cis-diaminedichloroplatin (II), CDDP) is part of the standard therapy for a number of solid tumors including Non-Small-Cell Lung Cancer (NSCLC). The initial response observed is in most cases only transient and tumors quickly become refractory to the drug. Tumor cell resistance to CDDP relies on multiple mechanisms, some of which still remain unknown. In search for such mechanisms, we examined the impact of CDDP on mRNA translation in a sensitive and in a matched resistant NSCLC cell line. We identified a set of genes whose mRNAs are differentially translated in CDDP resistant vs. sensitive cells. The translation of the mRNA encoding the Ubiquitin-Specific Peptidase 1 (USP1), a Ubiquitin peptidase with important function in multiple DNA repair pathways, is inhibited by CDDP exposure in the sensitive cells, but not in the resistant cells. This lack of down-regulation of USP1 expression at the translational level plays a primary role in CDDP resistance since inhibition of USP1 expression or activity by siRNA or the small molecule inhibitor ML323, respectively is sufficient to re sensitize resistant cells to CDDP. We involved the USP1 mRNA translation as a major mechanism of CDDP resistance in NSCLC cells and suggest that USP1 could be evaluated as a candidate predictive marker and as a therapeutic target to overcome CDDP resistance. More generally, our results indicate that analysis of gene expression at the level of mRNA translation is a useful approach to identify new determinants of CDDP resistance. PMID- 26825233 TI - Insulin patents and market exclusivities: unresolved issues. PMID- 26825234 TI - Country in Focus: diabetes epidemic poses challenge for health care in India. PMID- 26825235 TI - Dr Mike: Sharing health leads to better health. PMID- 26825236 TI - Modeling cyclic variations in sustained human performance as measured by reaction time and the flash visual evoked potential-P2. AB - Recent research suggests that sustained attention is punctuated by periodic lapses that produce cyclic variations in sustained human performance. Research conducted by our laboratory (Arruda, Zhang, Amoss, Coburn, & Aue, 2009) and by the laboratories of others (Aue, Arruda, Kass, & Stanny, 2009; Smith, Valentino, & Arruda, 2003) suggests that sustained human performance cycles approximately every 1.5 and 5.2min. Further, it has been suggested that a norepinephrine based arousal system may be responsible for these variations. Unfortunately, both cholinergic and noradrenergic pathways are known to mediate attention and it is unclear from previous research whether one or both of the identified cycles is related to cholinergic functioning. Consequently, the purpose of the present investigation was to assess the validity of the 1.5 and the 5.2mincycles using both reaction time and a cortical marker of cholinergic activity-the flash visual evoked potential P2 (FVEP-P2). Twenty-seven participants performed a 15-min continuous performance task. A spectral analysis procedure was used to detect the prevalence of the 1.5 and 5.2mincycles in both performance and cortical activity. While the results of these analyses support the validity of the 1.5 and 5.2mincycles in sustained human performance, only the 5.2mincycle was detected in cortical activity (i.e., the FVEP-P2 amplitudes) using model fitting. Consequently, the results of the present investigation support the validity of the 1.5 and 5.2mincycles and extend the findings of previous research by implicating acetylcholine in the 5.2mincycle. PMID- 26825237 TI - On Simple Structure and the Solution to Thurstone's Invariant Box Problem. AB - Thurstone's invariant box problem has 2 features which prevent the finding of the obvious simple structure by any of the usual analytic methods of rotation. PMID- 26825238 TI - On Obtaining the Best Estimates of Factor Scores Within An Ideal Simple Structure. AB - With the specification of a theoretical model and computer generation of a conforming population, 2 frameworks for evaluating the goodness of factor score estimation were constructed. PMID- 26825239 TI - Relating Factors Between Studies Based Upon Different Individuals. AB - A method for relating factors between studies based on different individuals is developed. This approach yields a measure of reltionship between all factors under consideration, a measure which may be interpreted as a correlation coefficient. PMID- 26825240 TI - Image Analysis Illustrated With A Spearman Case. AB - Because one can write the inverse of the correlation matrix in an extremely simple fashion when the variables form a perfect Spearman case, it is possible to use such a case to illustrate some well-known princeples in component and factor analysis. PMID- 26825241 TI - The Effect of Task on Intra-Individual Differences in Similarities Judgments. AB - In a recent MBR article (1969), Fenker and Brown discuss the relationship between task spaces and conceptual space in the multidimensional scaling of similarities judgments. This article extends some of their research to the case of multiple judges and real stimuli: a set of 20 bakery-type food items. In addition, we examine the relationship between overall similarities judgments and task specified similarities judgments. PMID- 26825242 TI - Semantic Differential Factor Structure Stability Across Subject, Concept, and Time Differences. AB - Semantic differential ratings by 90 students at the University of Maryland toward 6 political concepts were obtained before and after the 1964 Presidential Election. When the repsonses of Johnson and Goldwater supporters ere combined in a single factor analysis, 2 factors were extracted. These are described as the evaluative factor and a dynamism factor. PMID- 26825243 TI - Interrelatedness With Others as a Measure of Psychological Stability. AB - Psychological disturbance is presumed to express itself in a relatively small and unique patter of responses; a disturbed individual is somewhat unlike most other individuals, both normal and disturbed. A pertinent assessment approach is to select a representative scoring sample. Using the answer sheets of these subjects as keys, all other subjects are scored on them. A subject's total score is the sume of his scores on the answer sheets of the scoring sample. PMID- 26825244 TI - A FACTOR ANALYTIC STUDY OF COMMUNICATION SKILLS AND NONVERBAL ABILITIES OF DEAF REHABILITATION CLIENTS. AB - As part of the routine service procedures, 159 profoundly deaf rehabilitation candidates wre extensively tested on a variety of nonverbal intelligence and ability measures and rated on 10 communication variables. Two principal components factor analyses followed by Varimax rotations were performed, one on the total sample which spanned the age range from 16 to 67 years, and the second on a subsample of 87 clients between the ages of 16 and 25 years. PMID- 26825245 TI - A FACTOR ANALYTICAL STUDY OF INTELLECTUAL AND NON-INTELLECTUAL CHARACTERISTICS. AB - Tests of personality, interests, intelligence, and academic achievement were administered by 271 Ss. The data were processed by the principal component method of factor analysis. Twelve second-order factors were extracted and interpreted after oblique maxplane rotation. PMID- 26825246 TI - Retrospective analysis of reproductive outcomes in women with primary ovarian insufficiency showing intermittent follicular development. AB - The aim of this retrospective study was to explore the reproductive outcomes of IVF treatment in women with primary ovarian insufficiency (POI) showing intermittent follicular development. A total of 44 POI women with normal karyotype and absent autoimmunity, attending the centre for fertility treatment at Nanfang Hospital, Guangzhou from March 2009 to March 2011, were identified as suitable for inclusion in this study. Out of 44 women, 20 (20/44; 45.5%) had growing follicles and 13 underwent 27 oocyte retrievals. The empty follicle rate per oocyte retrieval was 70.4% (19/27); eight oocytes were recovered: one (12.5%) germinal vesicle (GV), two (25.0%) metaphase I (MI), one (12.5%) metaphase II (MII), and four (50.0%) atretic. One MI oocyte matured in vitro and two women had embryo transfer. Only the woman with the MI oocyte matured in vitro conceived, giving birth to a healthy baby at term. These results suggest that intermittent follicular development is common in women with POI but most of the developed follicles are empty or contain atretic oocytes. The pregnancy rate remains very low for IVF treatment. PMID- 26825247 TI - Ovarian tissue cryopreservation and retransplantation--what do patients think about it? AB - Cryopreservation of ovarian tissue has been successfully applied clinically, with over 60 live births to date. The aim of the present study was to perform a survey of patients who have had ovarian tissue cryopreserved in the Department of Obstetrics and Gynecology, Erlangen University Hospital, in order to obtain information about: why patients opt for fertility preservation; their current fertility; pregnancy attempts and outcomes; and their intended plans for the cryopreserved ovarian tissue. In total, 147 women took part in the survey (average age 25.0 +/- 7.0 years; response rate 48%; mean follow-up period 6 years). Sixty-six reported regular menstrual cycles; 48 were amenorrhoeic. Sixty two women had tried to conceive; 33 reported pregnancies. Twenty-five had delivered healthy children after conceiving naturally; eight had conceived with assisted reproduction. Five patients had had their ovarian tissue retransplanted. Although many patients continued to have ovarian function, none of them regretted choosing cryopreservation of ovarian tissue. Cryopreservation of ovarian tissue is an effective option and is very important for women diagnosed with cancer. Analyses of the clinical outcomes in these patients are essential in order to identify those patients capable of benefiting most from the procedure and in order to improve the technique. PMID- 26825248 TI - Human Papillomavirus Vaccination. PMID- 26825249 TI - Teaching Parents How to Prevent Acquired Cranial Asymmetry in Infants. AB - Acquired cranial asymmetry is prevalent in infants today. This is largely attributed to the supine sleep position recommended for infant safety. The condition can become permanent, so prevention and early detection are important. A prevention project was initiated where guidelines for Swedish child health nurses were developed, tested in a pilot study, revised, and then incorporated into a short cranial asymmetry prevention program for nurses. The program included detailed information on what to teach parents of newborns. An intervention study was initiated where one group of nurses was taught according to the program and the other group followed the standard recommendations. The aim of this survey was to compare intervention and control group parents' responses regarding the cranial asymmetry prevention information that they had received from their nurses during their infant's first four months. Participants included 272 parents (180 intervention group, 92 control group) at 26 child health centers. A checklist was distributed to parents in conjunction with infants' four month health checkup. A significantly higher percentage of intervention group parents were aware of regular recommendations - alternate direction of the infant's head when putting the child to bed (82%: 64%, p=0.001), which pillow to use (92%: 80%, p=0.01), and when to remove the pillow (48%: 31%, p=0.006) - and five newly introduced recommendations compared to controls. Results indicate that educating child health nurses on prevention of cranial asymmetry works to increase parental awareness of what to do and how to do it safely. PMID- 26825250 TI - Establishment of practice standards in nomenclature and prescription to enable construction of software and databases for knowledge-based practice review. AB - INTRODUCTION: Establishment of standards within a practice and across disease site groups for nomenclatures, prescription formatting, and measured dose-volume histogram (DVH) metrics is a key enabling step for creating software and database solutions to make routine aggregation of dosimetric data for all patients treated in a practice, practical. A process of physician-driven, iterative dialogs coupled with development of technical tools is required to implement the cultural and procedural changes. The cumulative reward for this effort is a database that can be used for defining practice norms, benchmarking against national standards, and tracking dosimetric effects of longitudinal practice pattern changes. METHODS AND MATERIALS: A 4-year project was carried out to develop and introduce standardizations, modify processes, and develop computer-based tools for reporting, aggregation, and analysis of prescription and DVH metrics. Physician disease site groups developed 42 target and 81 normal tissue templates. From the database of 32,002 DVH metrics, benchmarking was illustrated for a subgroup of breast (281) and prostate (324) patients treated with conventional fractionation over a 16-month period. Breast patients were segregated according to prescription template used: simple (S, tangents only) vs complex (C, tangents + supraclavicular +/- intramammary nodes) and left (S-L or C-L) versus right (S-R or C-R). RESULTS: Prostate patients' median and 50% confidence intervals (CIs) for bladder, stated according to the nomenclature: the percentage of bladder volume receiving doses of >=40 Gy (V40[%]), V65Gy[%], V70Gy[%], V75Gy[%], and V80Gy[%] were 45.5 (24.9-57.0), 15.6 (9.0-23.8), 7.6 (3.3-13.6), 2.0 (0.0-7.9), and 0.0 (0.0-1.4), respectively. Values for rectum: V50Gy[%], V60 Gy[%], V65Gy[%], V70Gy[%], and V75Gy[%] were 37.1 (27.8-43.5), 21.8 (15.6-25.5), 14.6 (9.6-18.0), 7.7 (1.9-12.3), and 1.0 (0-7.0), respectively. For breast patients, heart:mean Gray values were 1.5 (1.0-2.0), 3.1 (2.2-4.8), 0.4 (0.3-0.7), and 1.1 (0.8-2.2) for S-L, C-L, S-R, and C-R, respectively. Longitudinal, moving window plots of median, 50% CI, and 90% CI for 6-month periods demonstrated the effect of practice changes to reduce heart doses. CONCLUSIONS: Standardization was challenging as a practice change, but has resulted in significant improvements for both our clinical and research efforts. PMID- 26825251 TI - Phenylethanoid glycosides of Pedicularis muscicola Maxim ameliorate high altitude induced memory impairment. AB - Exposure to hypobaric hypoxia causes oxidative stress, neuronal degeneration and apoptosis that leads to memory impairment. Though oxidative stress contributes to neuronal degeneration and apoptosis in hypobaric hypoxia, the ability for phenylethanoid glycosides of Pedicularis muscicola Maxim (PhGs) to reverse high altitude memory impairment has not been studied. Rats were supplemented with PhGs orally for a week. After the fourth day of drug administration, rats were exposed to a 7500 m altitude simulation in a specially designed animal decompression chamber for 3 days. Spatial memory was assessed by the 8-arm radial maze test before and after exposure to hypobaric hypoxia. Histological assessment of neuronal degeneration was performed by hematoxylin-eosin (HE) staining. Changes in oxidative stress markers and changes in the expression of the apoptotic marker, caspase-3, were assessed in the hippocampus. Our results demonstrated that after exposure to hypobaric hypoxia, PhGs ameliorated high altitude memory impairment, as shown by the decreased values obtained for reference memory error (RME), working memory error (WME), and total error (TE). Meanwhile, administration of PhGs decreased hippocampal reactive oxygen species levels and consequent lipid peroxidation by elevating reduced glutathione levels and enhancing the free radical scavenging enzyme system. There was also a decrease in the number of pyknotic neurons and a reduction in caspase-3 expression in the hippocampus. These findings suggest that PhGs may be used therapeutically to ameliorate high altitude memory impairment. PMID- 26825253 TI - Predominance of modern Mycobacterium tuberculosis strains and active transmission of Beijing sublineage in Jayapura, Indonesia Papua. AB - Mycobacterium tuberculosis genotype distribution is different between West and Central Indonesia, but there are no data on the most Eastern part, Papua. We aimed to identify the predominant genotypes of M. tuberculosis responsible for tuberculosis in coastal Papua, their transmission, and the association with patient characteristics. A total of 199 M. tuberculosis isolates were collected. Spoligotyping was applied to describe the population structure of M. tuberculosis, lineage identification was performed using a combination of lineage specific markers, and genotypic clusters were identified using a combination of 24-locus-MIRU-VNTR and spoligotyping. A high degree of genetic diversity was observed among isolates based on their spoligopatterns. Strains from modern lineage 4 made up almost half of strains (46.9%), being more abundant than the ancient lineage 1 (33.7%), and modern lineage 2 (19.4%). Thirty-five percent of strains belonged to genotypic clusters, especially strains in the Beijing genotype. Previous TB treatment and mutations associated with drug resistance were more common in patients infected with strains of the Beijing genotype. Papua shows a different distribution of M. tuberculosis genotypes compared to other parts of Indonesia. Clustering and drug resistance of modern strains recently introduced to Papua may contribute to the high tuberculosis burden in this region. PMID- 26825252 TI - Genetic diversity of the Plasmodium falciparum apical membrane antigen I gene in parasite population from the China-Myanmar border area. AB - To investigate the genetic diversity of the Plasmodium falciparum apical membrane antigen 1 (PfAMA1) gene in Southeast Asia, we determined PfAMA1 sequences from 135 field isolates collected from the China-Myanmar border area and compared them with 956 publically available PfAMA1 sequences from seven global P. falciparum populations. This analysis revealed high genetic diversity of PfAMA1 in global P. falciparum populations with a total of 229 haplotypes identified. The genetic diversity of PfAMA1 gene from the China-Myanmar border is not evenly distributed in the different domains of this gene. Sequence diversity in PfAMA1 from the China-Myanmar border is lower than that observed in Thai, African and Oceanian populations, but higher than that in the South American population. This appeared to correlate well with the levels of endemicity of different malaria-endemic regions, where hyperendemic regions favor genetic cross of the parasite isolates and generation of higher genetic diversity. Neutrality tests show significant departure from neutrality in the entire ectodomain and Domain I of PfAMA1 in the China-Myanmar border parasite population. We found evidence supporting a substantial continent-wise genetic structure among P. falciparum populations, with the highest genetic differentiation detected between the China-Myanmar border and the South American populations. Whereas no alleles were unique to a specific region, there were considerable geographical differences in major alleles and their frequencies, highlighting further necessity to include more PfAMA1 alleles in vaccine designs. PMID- 26825254 TI - Characterization of sprays for thermo-stabilized pneumatic nebulizer. AB - The research presents the nebulizer spray chamber temperature controller responsible for controlling temperature of aerosol produced as a result of nebulizing process. The motivation to make an attempt to improve modern pneumatic devices was the shortage of this kind of apparatuses on the market allowing the production of thermos aerosol. A designed temperature controlling system for pneumatic nebulizers aims at increasing and stabilizing temperature of produced aerosols and increasing aerosol therapy safety. The system is intended for producing aerosol in the process of pneumatic nebulization with the temperature similar to that of the human body. Experiments that were carried out confirmed good performance of the device. It was proved that with the increase of temperature the amount of big droplets fall and the entire spectrum of the droplet diameter moves towards smaller droplet diameter values. Reduction of liquid viscosity related to the increase of temperature leads to the reduction of droplet diameter and, as a result, the reduction of the Sauter mean diameter value. PMID- 26825255 TI - Recent Advances in Factors and Methods for Stimulation of Biomethane Production. AB - The role of methanogenesis in the global carbon cycle is very important for recycle of renewable biomass which, has the potential for contribution to independence from fossil fuels. Anaerobic microbes comprised of fermentative and acetogenic species decompose the complex biomass to hydrogen, formate and, acetate that are further metabolized to methane by methanogens. A general review of biogenic production of methane and methanogenic diversity involved is presented. This review gives an overview of recent patents on methane production and focuses mainly on different methods, systems and, microbial methanogenic community involved in anaerobic digestion that can be used for improved understanding of the microbial community function and relationships in methanogenesis. PMID- 26825256 TI - Fatal Falls in New York City: An Autopsy Analysis of Injury Patterns. AB - INTRODUCTION: Falls from heights are an important cause of unintentional fatal injury. We investigated the relationship between the characteristics of fatal falls and resulting injury patterns. MATERIALS AND METHODS: We reviewed prospectively collected data from the Office of Chief Medical Examiner in New York City between 2000 and 2010. Data included fall height, work or non-work related, use of safety equipment, intentionality, specific organ injuries, and death on impact. The primary outcome was organ injury based on fall height. RESULTS: Higher falls were associated with hemorrhage as well as rib and various organ injuries. Organ injury pattern did not differ based on work status. The presence of equipment misuse or malfunction was associated with more deaths upon impact. Victims of falls from 200 ft or higher were 11.59 times more likely to die on impact than from lower than 25 ft. CONCLUSIONS: Fall height and work related falls were significantly associated with death on impact. This is a public health issue, as 13% of falls were work related and 4% of falls were due to improper use of safety equipment. Some work-related falls are potentially preventable with proper safety equipment use. Understanding patterns of injury may play a role in prevention and management of survivors in the acute period. PMID- 26825257 TI - Constructing a validated scale to measure community-level abortion stigma in Mexico. AB - OBJECTIVE: In Mexico, abortion stigma in the general population is largely unexplored. We developed a scale to measure abortion stigma at the community level, examine its prevalence and explore factors associated with abortion stigma in a nationally representative sample. STUDY DESIGN: Following intensive qualitative work to identify dimensions of the stigma construct, we developed a comprehensive list of statements that were cognitively tested and reduced to 33 to form a scale. We piloted the scale in a nationally and subregionally representative household public opinion survey administered to 5600 Mexican residents. RESULTS: Factor analysis tested the internal consistency and reliability of five previously hypothesized dimensions of abortion stigma: secrecy, religion, autonomy, discrimination and guilt/shame. Under the assumption that these dimensions were independent, confirmatory factor analysis indicated that each of these dimensions functioned as independent subscales. However, to test this assumption, we conducted exploratory factor analysis that revealed a strong codependence between discrimination, guilt/shame and religion statements, resulting in a 23-item four-factor model of abortion stigma and the elimination of the guilt/shame dimension. Both methods revealed a full scale and subscales with Cronbach's alphas between 0.80 and 0.90. Regression analyses suggested that older, less educated individuals living in the north of Mexico report higher levels of stigma, especially related to discrimination and religion. CONCLUSIONS: This community-level abortion stigma scale is the first to be developed and tested in Mexico. This tool may be used in Mexico and other similar country settings to document the prevalence of community-level abortion stigma, identify associated factors and test interventions aimed at reducing abortion stigma. IMPLICATIONS: Abortion stigma prevents women from accessing safe abortion services. Measuring community-level abortion stigma is key to documenting its pervasiveness, testing interventions aimed at reducing it and understanding associated factors. This scale may be useful in countries similar to Mexico to support policymakers, practitioners and advocates in upholding women's reproductive rights. PMID- 26825258 TI - Cardiovascular risks associated with the use of drospirenone-containing combined oral contraceptives. AB - OBJECTIVES: The "Long-term Active Surveillance Study for Oral Contraceptives" investigated the risks of long-term use of a 21-day regimen of drospirenone and ethinylestradiol (DRSP) compared to established oral contraceptives (OCs) in a routine clinical setting. STUDY DESIGN: Prospective, controlled, non interventional cohort study conducted in seven European countries with three main exposure groups: new users of DRSP, levonorgestrel-containing OCs (LNG), and OCs containing other progestogens (Other OCs). All self-reported clinical outcomes of interest (OoI) were validated via attending physicians and relevant source documents. Main OoI were serious clinical outcomes, in particular cardiovascular events. Comprehensive follow-up procedures were implemented. Statistical analyses were based on Cox regression models. RESULTS: A total of 1,113 study centers enrolled 59,510 women. Overall 28%, 26% and 45% of these women used DRSP, LNG and Other OCs, respectively. Study participants were followed for up to ten years (mean value, 5.4years), which generated 318,784 woman-years (WY) of observation. Low loss to follow-up and drop-out rates of 2.9% and 16.8% were achieved. DRSP, LNG, and Other OCs showed similar incidence rates of venous thromboembolism. Corresponding hazard ratios (HRs) were close to unity. For arterial thromboembolic events (ATE) and initiation of antihypertensive treatment statistically significant lower risks were found for DRSP compared to LNG and Other OCs. CONCLUSION: DRSP use was associated with similar general health risks and a low risk of ATE compared to OCs containing other progestogens. IMPLICATION STATEMENT: The 21-day regimen of drospirenone-containing combined oral contraceptives is associated with similar risk of VTE compared to other combined oral contraceptives as well as potentially with a lower risk of ATE. PMID- 26825259 TI - Endoscopic ultrasound of the larynx. AB - PURPOSE OF REVIEW: Endoscopic ultrasound (EUS) of the larynx is a vertical endoscopic imaging technique that gives further information about the extension of a lesion apart from normal white light endoscopy, chromoendoscopy, as well as palpation. It combines the advantages of ultrasound and endoscopy. Miniprobes or ultrasound endoscopes with 10-20 MHz are applied. The present review is focused on the use of EUS in the larynx especially in the management of laryngeal cancer. RECENT FINDINGS: At present, the larynx is routinely assessed by computed tomography and MRI. Alternatively, endoscopic endoluminal application of miniprobes enables the laryngologist to predict the exact extension of a laryngeal tumor larger than 3 mm during microlaryngoscopy before surgery is performed. Generally, tumors are hypoechoic and can easily be differentiated from the surrounding tissue especially in the hyperechoic supraglottic structures. Thyroid cartilage infiltration can be detected by the interruption of the hyperechoic inner perichondrium. SUMMARY: EUS proved to be a reliable imaging tool for the investigation of laryngeal lesions and can easily be used during microlaryngoscopy. It offers a higher image resolution compared with computed tomography and MRI and allows a complete sonographic evaluation of the larynx as well as its pathological changes, especially laryngeal cancer. VIDEO FILE LINK: http://links.lww.com/COOH/A19. PMID- 26825260 TI - Retention efficacy and release of radioiodine in fume hoods. AB - Procedures to determine the release of hazardous gaseous substances including radioactive iodine are covered by different norms such as the European standard EN 14175 and the German national standard DIN 25466. The detection of sulphur hexafluoride (SF6) is required to comply with the prescribed methodology. The detection limit of this test is 4.5.10-7 mol/m3 in exhaust air. This detection limit would represent a very high activity in the region of 0.27 TBq/m3 leading to an unacceptable risk. We therefore developed a test using a filter system, consisting of a combination of filters capable of separating various chemical forms of airborne radioiodine. Air samples were collected directly in front of the fume hood and in the laboratory beside two different fume hoods of a similar construction with a final activated carbon filter for retention of radioiodine. Particular attention was therefore paid to air samples taken after passage over the filters. Significant differences in the degree of retention of iodine were found between the two fume hoods investigated. In one test a malfunction of the fume hood was demonstrated. In this case 0.148 * 10-3% of the total released activity per m3 air was found 1 cm in front of the hood sash. A remarkably high fraction of the activity released in the fume hood (1.3 * 10-3%/m3 air) was measured after the activated carbon filter. In the ambient air, values of up to 8.6 * 10-6% pro m3 laboratory air sampled were measured, despite a 6-8-fold air exchange. The selected procedure is a factor of 1011 (Schomacker et al., 2001) more sensitive than the standard recommended methods (EN 14175). The standard test prescribed by the DIN/EN failed to reveal any inadequacy in the protective function of the radionuclide hood with respect to radioiodine retention. PMID- 26825261 TI - A Bridge to Somewhere: 25-day Survival After Pig-to-Baboon Liver Xenotransplantation. PMID- 26825262 TI - Factors associated with reoperation in hypospadias surgery - A nationwide, population-based study. AB - BACKGROUND/OBJECTIVE: To analyze the preoperative factors associated with the need for secondary surgery following primary urethroplasty. METHODS: This study utilized a subset of the National Health Insurance Research Database, which includes the data on all paid medical benefit claims from 1997 to 2007, for 1 million beneficiaries in 2005. We analyzed the claims data for all patients with hypospadias who had undergone primary urethroplasty. The characteristics of the patients, surgeons, and hospitals associated with surgical outcomes were analyzed to investigate possible associations with the need for secondary surgery. RESULTS: Among 52,705 live male newborn babies, 218 were diagnosed with hypospadias, of whom 89 received repair surgery. A total of 75 (84.3%) male newborn babies received single hypospadias surgery, and 14 (15.7%) underwent more than two surgical procedures. Univariate analysis demonstrated that the type of hypospadias and the surgeon caseload volume were significantly associated with the need for additional hypospadias surgery (p = 0.02 and p = 0.03, respectively). In multivariate analysis, the type of hypospadias (distal vs. proximal, odds ratio, 0.25; p = 0.03) and the surgeon caseload volume (high vs. low, odds ratio, 0.04; p = 0.05) were significantly correlated with secondary operation. CONCLUSION: The type of hypospadias and the surgeon caseload volume were significantly associated with the need for secondary hypospadias surgery. The findings of this study provide important information on the outcomes of hypospadias repair for parents and specialists. PMID- 26825263 TI - Neurofeedback Treatment and Posttraumatic Stress Disorder: Effectiveness of Neurofeedback on Posttraumatic Stress Disorder and the Optimal Choice of Protocol. AB - Neurofeedback is an alternative, noninvasive approach used in the treatment of a wide range of neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). Many different neurofeedback protocols and methods exist. Likewise, PTSD is a heterogeneous disorder. To review the evidence on effectiveness and preferred protocol when using neurofeedback treatment on PTSD, a systematic search of PubMed, PsychInfo, Embase, and Cochrane databases was undertaken. Five studies were included in this review. Neurofeedback had a statistically significant effect in three studies. Neurobiological changes were reported in three studies. Interpretation of results is, however, limited by differences between the studies and several issues regarding design. The optimistic results presented here qualify neurofeedback as probably efficacious for PTSD treatment. PMID- 26825264 TI - Hypersensitivity to Contingent Behavior in Paranoia: A New Virtual Reality Paradigm. AB - Contingency in interpersonal relationships is associated with the development of secure attachment and trust, whereas paranoia arises from the overattribution of negative intentions. We used a new virtual reality paradigm to experimentally investigate the impact of contingent behavior on trust along the paranoia continuum. Sixty-one healthy participants were randomly allocated to have a social interaction with a pleasant virtual human (avatar) programmed to be highly responsive or not (high/low contingency). Perceived trustworthiness and trusting behavior were assessed alongside control variables attachment and anxiety. Higher paranoia and dismissive attachment were associated with larger interpersonal distances. Unexpectedly, extremely paranoid individuals experienced the highly contingent avatar as more trustworthy than their low contingency counterpart. Higher dismissive attachment was also associated with more subjective trust in both conditions. Extreme paranoia is associated with hypersensitivity to noncontingent behavior, which might explain experiences of mistrust when others are not highly responsive in everyday social situations. PMID- 26825265 TI - Somatic Symptoms Mediate the Relationship Between Trauma During the Arab Spring and Quality of Life Among Tunisians. AB - This study examined the relationship between peritraumatic reactions, posttraumatic stress disorder (PTSD) symptoms, somatic complaints, and quality of life in Tunisians exposed to the events of the Arab Spring. Participants (n = 60) completed an online survey 1 year after the events, assessing peritraumatic distress, peritraumatic dissociation, PTSD symptoms, somatic complaints, and physical and mental quality of life. Results showed that peritraumatic dissociation was independently associated with increased PTSD symptoms and somatic complaints 12 months after the events. Multiple mediator mediation analyses revealed that somatic complaints (not PTSD symptoms) were the only independent mediators of the relationships between peritraumatic dissociation and both physical and mental quality of life. Assessing peritraumatic dissociation soon after trauma exposure among the North African population might help identify individuals at risk for PTSD. Furthermore, the impact of trauma on quality of life may be better explained by somatic complaints than PTSD symptoms among North Africans. PMID- 26825266 TI - Caregiver Positive and Negative Appraisals: Effects of the National Alliance on Mental Illness Family-to-Family Intervention. AB - The 3-month-long Family-to-Family intervention (FTF) has been shown to increase empowerment, knowledge, and coping and to reduce distress among caregivers of people with serious mental illness. We sought to determine the influence of FTF on caregivers' appraisal of their caregiving experience. Family members of individuals with mental illness who sought enrollment in FTF (n = 318) were randomly assigned to FTF or a waitlist condition. Positive and negative appraisals were measured using the Experiences of Caregiving Inventory at baseline and 3 months later; 259 participants completed both assessments. Regression analyses found significant increases in positive appraisal but no significant decreases in negative appraisals for those in the FTF condition. In the context of overall benefits from taking FTF, these relationships reflect the FTF curriculum's emphasis on positive coping (e.g., strength and empowerment) and the potential value of strategies that help caregivers increase positive appraisal. PMID- 26825267 TI - High risk of malnutrition associated with depressive symptoms in older South Africans living in KwaZulu-Natal, South Africa: a cross-sectional survey. AB - BACKGROUND: Malnutrition contributes to functional and cognitive decline in older adults, which results in decreased quality of life and loss of independence. This study aimed to identify determinants of nutritional risk among community-dwelling adults in KwaZulu-Natal, South Africa. METHODS: A cross-sectional survey was undertaken in 1008 subjects aged 60 years and over who were randomly selected by systematic sampling. Demographics, socioeconomic data and self-reported history of medical conditions were recorded. The Mini Nutritional Assessment-Short Form (MNA-SF) was used to screen for nutritional risk, and the Centre for Epidemiologic Studies Depression scale was administered to all subjects. Descriptive statistics and the Pearson chi-square and Kruskal-Wallis tests were used for statistical analysis. Logistic regression modelling determined predictors of nutritional risk. RESULTS: Of the 984 participants (mean age = 68.8 +/- 7.4 years; range 60-103 years) who completed the MNA-SF, 51% were classified as having a normal nutritional status, 43.4% at risk for malnutrition and 5.5% classified as malnourished. Men were more likely to be either at risk for malnutrition or be malnourished than women (p = 0.008), as were subjects with a monthly household income of <=R1600 per month (~133 USD) (p = 0.003). In logistic regression models, depressed people were 2.803 (p < 0.001) times more likely to be at risk or be malnourished than those not depressed. CONCLUSION: A high prevalence of risk of malnutrition was identified in older South Africans living in an urban area with poor infrastructure. Further investigations are warranted to determine whether the higher prevalence of depressive symptomatology in nutritionally at risk individuals is a determinant or a consequence of malnutrition, in order to develop targeted nutritional interventions in this age group. PMID- 26825268 TI - The Prevalence of Substance Use and Other Mental Health Concerns Among American Attorneys. AB - OBJECTIVES: Rates of substance use and other mental health concerns among attorneys are relatively unknown, despite the potential for harm that attorney impairment poses to the struggling individuals themselves, and to our communities, government, economy, and society. This study measured the prevalence of these concerns among licensed attorneys, their utilization of treatment services, and what barriers existed between them and the services they may need. METHODS: A sample of 12,825 licensed, employed attorneys completed surveys, assessing alcohol use, drug use, and symptoms of depression, anxiety, and stress. RESULTS: Substantial rates of behavioral health problems were found, with 20.6% screening positive for hazardous, harmful, and potentially alcohol-dependent drinking. Men had a higher proportion of positive screens, and also younger participants and those working in the field for a shorter duration (P < 0.001). Age group predicted Alcohol Use Disorders Identification Test scores; respondents 30 years of age or younger were more likely to have a higher score than their older peers (P < 0.001). Levels of depression, anxiety, and stress among attorneys were significant, with 28%, 19%, and 23% experiencing symptoms of depression, anxiety, and stress, respectively. CONCLUSIONS: Attorneys experience problematic drinking that is hazardous, harmful, or otherwise consistent with alcohol use disorders at a higher rate than other professional populations. Mental health distress is also significant. These data underscore the need for greater resources for lawyer assistance programs, and also the expansion of available attorney-specific prevention and treatment interventions. PMID- 26825269 TI - Cannabis Use Disorders and ADHD. PMID- 26825270 TI - The Authors Reply to Cannabis Use Disorders and ADHD. PMID- 26825273 TI - Socio-economic determinants of household food security and women's dietary diversity in rural Bangladesh: a cross-sectional study. AB - BACKGROUND: There has been limited decline in undernutrition rates in South Asia compared with the rest of Asia and one reason for this may be low levels of household food security. However, the evidence base on the determinants of household food security is limited. To develop policies intended to improve household food security, improved knowledge of the determinants of household food security is required. METHODS: Household data were collected in 2011 from a randomly selected sample of 2,809 women of reproductive age. The sample was drawn from nine unions in three districts of rural Bangladesh. Multinomial logistic regression was conducted to measure the relationship between selected determinants of household food security and months of adequate household food provisioning, and a linear regression to measure the association between the same determinants and women's dietary diversity score. RESULTS: The analyses found that land ownership, adjusted relative risk ratio (RRR) 0.28 (CI 0.18, 0.42); relative wealth (middle tertile 0.49 (0.29, 0.84) and top tertile 0.18 (0.10, 0.33)); women's literacy 0.64 (0.46, 0.90); access to media 0.49 (0.33, 0.72); and women's freedom to access the market 0.56 (0.36, 0.85) all significantly reduced the risk of food insecurity. Larger households increased the risk of food insecurity, adjusted RRR 1.46 (CI 1.02, 2.09). Households with vegetable gardens 0.20 (0.11, 0.31), rich households 0.46 (0.24, 0.68) and literate women 0.37 (0.20, 0.54) were significantly more likely to have better dietary diversity scores. CONCLUSION: Household food insecurity remains a key public health problem in Bangladesh, with households suffering food shortages for an average of one quarter of the year. Simple survey and analytical methods are able to identify numerous interlinked factors associated with household food security, but wealth and literacy were the only two determinants associated with both improved food security and dietary diversity. We cannot conclude whether improvements in all determinants are necessarily needed to improve household food security, but new and existing policies that relate to these determinants should be designed and monitored with the knowledge that they could substantially influence the food security and nutritional status of the population. PMID- 26825274 TI - Bee venom acupuncture alleviates trimellitic anhydride-induced atopic dermatitis like skin lesions in mice. AB - BACKGROUND: Bee venom acupuncture (BVA), a novel type of acupuncture therapy in which purified bee venom is injected into the specific acupuncture point on the diseased part of the body, is used primarily for relieving pain and other musculoskeletal symptoms. In the present study, therapeutic potential of BVA to improve atopic dermatitis, a representative allergic dysfunction, was evaluated in the mouse model of trimellitic anhydride (TMA)-induced skin impairment. METHODS: Mice were treated with 5% TMA on the dorsal flank for sensitization and subsequently treated with 2% TMA on the dorsum of both ears for an additional 12 days after a 3-day interval. From the 7(th) day of 2% TMA treatment, bilateral subcutaneous injection of BV (BV, 0.3 mg/kg) was performed daily at BL40 acupuncture points (located behind the knee) 1 h before 2% TMA treatment for 5 days. RESULTS: BVA treatment markedly inhibited the expression levels of both T helper cell type 1 (Th1) and Th2 cytokines in ear skin and lymph nodes of TMA treated mice. Clinical features of AD-like symptoms such as ear skin symptom severity and thickness, inflammation, and lymph node weight were significantly alleviated by BV treatment. BV treatment also inhibited the proliferation and infiltration of T cells, the production of Th1 and Th2 cytokines, and the synthesis of interleukin (IL)-4 and immunoglobulin E (IgE)-typical allergic Th2 responses in blood. The inhibitory effect of BVA was more pronounced at BL40 acupoint than non-acupuncture point located at the base of the tail. CONCLUSIONS: These results indicate that BV injection at specific acupuncture points effectively alleviates AD-like skin lesions by inhibiting inflammatory and allergic responses in a TMA-induced contact hypersensitivity mouse model. PMID- 26825275 TI - Are there changes in the nutritional status of children of Oportunidades families in rural Chiapas, Mexico? A cohort prospective study. AB - BACKGROUND: In Mexico, despite that the fact that several social programs have been implemented, chronic undernutrition is still a public health problem affecting 1.5 million children of <5 years. Chiapas ranks first in underweight and stunting at national level with a stunting prevalence of 31.4 % whereas for its rural population is 44.2 %. The purpose of this paper is to determine if the nutritional status of a cohort of children living in poor rural communities under Oportunidades has changed. We were interested in assessing the nutrition evolution of the children who were initially diagnosed as stunted and of those who were diagnosed as normal. Oportunidades is an anti-poverty program of the Mexican government consisting mainly in monetary transfers to the families living in alimentary poverty. METHODS: A 9-year cohort prospective study was conducted with nutritional evaluations of 222 children. Anthropometric indices were constructed from measurements of weight, height, and age of the children whose nutritional status was classified following WHO standards. RESULTS: The results showed that although these children were Oportunidades beneficiaries for 9 years and their families improved their living conditions, children still had a high prevalence of stunting (40.1 %) and 69.6 % had not recovered yet. Children who were initially diagnosed with normal nutritional status and became stunted 2 years later had a higher risk (relative risk (RR) 5.69, 2.95-10.96) of continuing stunted at school age and adolescence. CONCLUSIONS: Oportunidades has not impacted, as expected, the nutritional status of the study population. These findings pose the question: Why has not the nutritional status of children improved, although the living conditions of their families have significantly improved? This might be the result of an adaptation process achieved through a decrease of growth velocity. It is important to make efforts to watch the growth of the children during their first 3 years of age, to focus on improving the diet of women at fertile age and pay special attention to environmental conditions to break the vicious cycle of malnutrition. PMID- 26825276 TI - Sex differences in morbidity and care-seeking during the neonatal period in rural southern Nepal. AB - BACKGROUND: South Asian studies, including those from Nepal, have documented increased risk of neonatal mortality among girls, despite their early biologic survival advantage. We examined sex differences in neonatal morbidity and care seeking behavior to determine whether such differences could help explain previously observed excess late neonatal mortality among girls in Nepal. METHODS: A secondary analysis of data from a trial of chlorhexidine use among neonates in rural Nepal was conducted. The objective was to examine sex differences in neonatal morbidity and care-seeking behavior for ill newborns. Girls were used as the reference group. RESULTS: Referral for care was higher during the early neonatal period (ENP: 0-7 days old) (50.7%) than the late neonatal period (LNP: 8 28 days old) (31.3%), but was comparable by sex. There were some significant differences in reasons for referral by sex. Boys were significantly more often referred for convulsions/stiffness, having yellow body/eyes, severe skin infection, and having at least two of the following: difficulty breathing, difficulty feeding, fever, or vomiting during the ENP. Girls were more often referred for hypothermia. During the LNP, boys were significantly more often referred for having yellow body/eyes, persistent watery stool, and severe skin infection. There were no referral types in the LNP for which girls were more often referred. Less than half of those referred at any point were taken for care (47.0%) and referred boys were more often taken than girls (Neonatal Period OR: 1.77, 95% CI: 1.64 - 1.91). Family composition differentially impacted the relationship between care-seeking and sex. The greatest differences were in families with only prior living girls (Pahadi - ENP OR: 1.78, 95% CI: 1.29 - 2.45 and LNP OR: 1.51, 95% CI: 1.03 - 2.21; Madeshi - ENP OR: 2.86, 95% CI: 2.28 - 3.59 and LNP OR: 2.45, 95% CI: 1.84 - 3.26). CONCLUSIONS: Care-seeking was inadequate for both sexes, but ill boys were consistently more often taken for care than girls, despite comparable referral. Behavioral interventions to improve care-seeking, especially in the early neonatal period, are needed to improve neonatal survival. Addressing gender bias in care-seeking, explicitly and within interventions, is essential to reducing neonatal mortality differentials between boys and girls. PMID- 26825277 TI - Complementary feeding practices and associated factors among HIV positive mothers in Southern Ethiopia. AB - The objective of this study was to assess complementary feeding practices and associated factors among HIV exposed infants in Sidama Zone, Southern Ethiopia. An institutional based cross-sectional study with cluster random sampling technique was employed and all HIV exposed infants aged 6-17 months found in randomly selected health institutions in Sidama zone, Southern Ethiopia were included. A 24-hour dietary recall and 7-day quasi-food group frequency was used to assess complementary feeding practices. The prevalence of timely initiation of complementary feeding (6-8 months) was 42% [95% CI: (30-54%)]. Of all the HIV exposed infants aged 6-17 months, 40.7% had practiced bottle-feeding. About 65.6% and 53.3% of HIV exposed infants did not receive the recommended number of food groups and frequency of complementary feeding in the last 24 hours respectively. Pulse (plant protein) was consumed by only 22.5% of the infants while only 9.9% of the infants consumed animal source food in the last 24 hours. Presence of infant food prohibition (beta = -0.342, P = 0.001) and age of the infant (beta = 0.311, P = 0.001) were found to be an independent predictors of dietary diversity. Presence of infant food prohibition (beta = -0.181, P = 0.02) and age of infant (beta = 0.388, P < 0.001) were also the predictors of 24 hour meal frequency. Having lower educational status [AOR = (0.21, 95% CI (0.062-0.71)] was an independent negative predictor of bottle-feeding practice. Many of the complementary feeding practices like meal frequency; dietary diversity and bottle feeding were sub-optimal. Nutrition education should be designed for improving complementary feeding practices of HIV exposed infants in Sidama Zone, Southern Ethiopia. Mothers with higher educational status should be also targeted for nutrition education especially on bottle feeding practice. PMID- 26825278 TI - Muscle mass, strength and functional outcomes in critically ill patients after cardiothoracic surgery: does neuromuscular electrical stimulation help? The Catastim 2 randomized controlled trial. AB - BACKGROUND: The effects of neuromuscular electrical stimulation (NMES) in critically ill patients after cardiothoracic surgery are unknown. The objectives were to investigate whether NMES prevents loss of muscle layer thickness (MLT) and strength and to observe the time variation of MLT and strength from preoperative day to hospital discharge. METHODS: In this randomized controlled trial, 54 critically ill patients were randomized into four strata based on the SAPS II score. Patients were blinded to the intervention. In the intervention group, quadriceps muscles were electrically stimulated bilaterally from the first postoperative day until ICU discharge for a maximum of 14 days. In the control group, the electrodes were applied, but no electricity was delivered. The primary outcomes were MLT measured by ultrasonography and muscle strength evaluated with the Medical Research Council (MRC) scale. The secondary functional outcomes were average mobility level, FIM score, Timed Up and Go Test and SF-12 health survey. Additional variables of interest were grip strength and the relation between fluid balance and MLT. Linear mixed models were used to assess the effect of NMES on MLT, MRC score and grip strength. RESULTS: NMES had no significant effect on MLT. Patients in the NMES group regained muscle strength 4.5 times faster than patients in the control group. During the first three postoperative days, there was a positive correlation between change in MLT and cumulative fluid balance (r = 0.43, P = 0.01). At hospital discharge, all patients regained preoperative levels of muscle strength, but not of MLT. Patients did not regain their preoperative levels of average mobility (P = 0.04) and FIM score (P = 0.02) at hospital discharge, independent of group allocation. CONCLUSIONS: NMES had no effect on MLT, but was associated with a higher rate in regaining muscle strength during the ICU stay. Regression of intramuscular edema during the ICU stay interfered with measurement of changes in MLT. At hospital discharge patients had regained preoperative levels of muscle strength, but still showed residual functional disability and decreased MLT compared to pre-ICU levels in both groups. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02391103. Registered on 7 March 2015. PMID- 26825280 TI - Agreement Between Autorefraction and Subjective Refraction in Keraring-Implanted Keratoconic Eyes. AB - OBJECTIVES: To assess the agreement between subjective refraction and autorefraction and to explore the relationship between the magnitude of higher order aberration, and visual acuity and refraction, before and after keraring implantation. METHODS: This prospective, randomized, interventional study enrolled 27 subjects (mean age 28.1+/-6.5 years) with keratoconus. Noncycloplegic refraction was performed subjectively by one clinician and with an autorefractor by another clinician, before and 6 months after surgery. The limit of agreement (LoA) between methods was assessed, and the relationships between the corrected distance visual acuity, logMAR on the one hand and refraction measurements and higher-order aberrations on the other, were examined. RESULTS: The agreement in mean spherical equivalent refraction (MSER) between methods was good postoperatively but poor preoperatively. The autorefractor gave a more myopic refraction than subjective refraction preoperatively (-3.28+/-3.06 D; LoA -9.27 to +2.71 D, P<0.0001) and postoperatively (-0.63+/-1.64 D; LoA -3.85 to +2.58 D, P=0.055), and returned higher negative cylinders preoperatively (-1.10+/-1.17 D; LoA -3.40 to +1.19 D, P<0.0001) and postoperatively (-1.08+/-1.27 D; LoA -3.60 to +1.41 D, P<0.0001) in keratoconic eyes. The difference in MSER between methods was significantly related to the refractive error at both visits (P<0.05) and to the magnitude of higher-order aberrations in keratoconic eyes preoperatively (P<0.05). The logMAR visual acuity achieved subjectively worsened as the magnitude of higher-order aberrations increased preoperatively (P<0.001). CONCLUSIONS: The autorefractor returns values that are significantly more myopic in MSER and higher negative cylinders than subjective refraction, preoperatively, but the MSER was similar between devices postoperatively. The autorefactor seems a valid starting point for subjective refraction in keratoconic eyes treated with keraring, but the cylinder should be corrected by about +1 D. The instruments agree more in less myopic than high myopic eyes. PMID- 26825279 TI - Genomic BLUP including additive and dominant variation in purebreds and F1 crossbreds, with an application in pigs. AB - BACKGROUND: Most developments in quantitative genetics theory focus on the study of intra-breed/line concepts. With the availability of massive genomic information, it becomes necessary to revisit the theory for crossbred populations. We propose methods to construct genomic covariances with additive and non-additive (dominance) inheritance in the case of pure lines and crossbred populations. RESULTS: We describe substitution effects and dominant deviations across two pure parental populations and the crossbred population. Gene effects are assumed to be independent of the origin of alleles and allelic frequencies can differ between parental populations. Based on these assumptions, the theoretical variance components (additive and dominant) are obtained as a function of marker effects and allelic frequencies. The additive genetic variance in the crossbred population includes the biological additive and dominant effects of a gene and a covariance term. Dominance variance in the crossbred population is proportional to the product of the heterozygosity coefficients of both parental populations. A genomic BLUP (best linear unbiased prediction) equivalent model is presented. We illustrate this approach by using pig data (two pure lines and their cross, including 8265 phenotyped and genotyped sows). For the total number of piglets born, the dominance variance in the crossbred population represented about 13 % of the total genetic variance. Dominance variation is only marginally important for litter size in the crossbred population. CONCLUSIONS: We present a coherent marker-based model that includes purebred and crossbred data and additive and dominant actions. Using this model, it is possible to estimate breeding values, dominant deviations and variance components in a dataset that comprises data on purebred and crossbred individuals. These methods can be exploited to plan assortative mating in pig, maize or other species, in order to generate superior crossbred individuals in terms of performance. PMID- 26825281 TI - Clinical Trial of Thermal Pulsation (LipiFlow) in Meibomian Gland Dysfunction With Preteatment Meibography. AB - OBJECTIVES: Thermal pulsation (LipiFlow) has been advocated for meibomian gland dysfunction (MGD) treatment and was found useful. We aimed to evaluate the efficacy and safety of thermal pulsation in Asian patients with different grades of meibomian gland loss. METHODS: A hospital-based interventional study comparing thermal pulsation to warm compresses for MGD treatment. Fifty patients were recruited from the dry eye clinic of a Singapore tertiary eye hospital. The ocular surface and symptom were evaluated before treatment, and one and three months after treatment. Twenty-five patients underwent thermal pulsation (single session), whereas 25 patients underwent warm compresses (twice daily) for 3 months. Meibomian gland loss was graded using infrared meibography, whereas function was graded using the number of glands with liquid secretion. RESULTS: The mean age (SD) of participants was 56.4 (11.4) years in the warm compress group and 55.6 (12.7) years in the thermal pulsation group. Seventy-six percent of the participants were female. Irritation symptom significantly improved over 3 months in both groups (P<0.01), whereas tear breakup time (TBUT) was modestly improved at 1 month in only the thermal pulsation group (P=0.048), without significant difference between both groups over the 3 months (P=0.88). There was also no significant difference in irritation symptom, TBUT, Schirmer test, and gland secretion variables between patients with different grades of gland loss or function at follow-ups. CONCLUSIONS: A single session of thermal pulsation was similar in its efficacy and safety profile to 3 months of twice daily warm compresses in Asians. Treatment efficacy was not affected by pretreatment gland loss. PMID- 26825282 TI - Could psychiatric assessment before hematopoietic stem cell transplantation predict the need for psychiatric consultation during transplantation period? AB - Psychiatric morbidity seems to be a significant concern associated with all stages of hematopoietic stem cell transplantation (HSCT). We aimed to understand whether psychiatric consultation before HSCT procedure could predict the need for psychiatric support during isolation period. Seventy-eight patients undergoing HSCT were included in the study. Patients were diagnosed according to the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV). Standard anxiety and depression scores were performed. Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and State and Trait Anxiety Inventory (STAI) were performed. Psychiatric consultation was required for 45 (58%) patients during hospitalization. Only pre-HSCT STAI trait scores were higher in patients who were found to have psychopathology at consultation during hospitalization compared to patients without established psychopathology. Sixteen (76%) and 29 (51%) patients needed consultation with and without pre-HSCT psychopathology, respectively. Our study showed that the psychiatric consultation request rate during the transplantation process was higher for cases previously diagnosed with psychopathology and who had high trait anxiety scale scores before HSCT. PMID- 26825283 TI - Central venous pressure: soon an outcome-associated matter. AB - PURPOSE OF REVIEW: Central venous pressure (CVP) alone has so far not found a place in outcome prediction or prediction of fluid responsiveness. Improved understanding of the interaction between mean systemic pressure (Pms) and CVP has major implications for evaluating volume responsiveness, heart performance and potentially patient outcomes. RECENT FINDINGS: The literature review substantiates that CVP plays a decisive role in causation of operative haemorrhage and renal failure. The review details CVP as a variable integral to cardiovascular control in its dual role of distending the diastolic right ventricle and opposing venous return. SUMMARY: The implication for practice is in the regulation of the circulation. It is demonstrated that control of the blood pressure and cardiac output/venous return calls upon regulation of the volume state (Pms), the heart performance (Eh) and the systemic vascular resistance. Knowledge of the CVP is required to calculate all three. PMID- 26825284 TI - Identification of new palmitoylated proteins in Toxoplasma gondii. AB - Protein palmitoylation has been shown to be an important post-translational modification in eukaryotic cells. This modification alters the localization and/or the function of the targeted protein. In recent years, protein palmitoylation has risen in importance in apicomplexan parasites as well. In Toxoplasma gondii, some proteins have been reported to be modified by palmitate. With the development of new techniques that allow the isolation of palmitoylated proteins, this significant post-translational modification has begun to be studied in more detail in T. gondii. Here we describe the palmitoylome of the tachyzoite stage of T. gondii using a combination of the acyl-biotin exchange chemistry method and mass spectrometry analysis. We identified 401 proteins found in multiple cellular compartments, with a wide range of functions that vary from metabolic processes, gliding and host-cell invasion to even regulation of transcription and translation. Besides, we found that more rhoptry proteins than the ones already described for Toxoplasma are palmitoylated, suggesting an important role for this modification in the invasion mechanism of the host-cell. This study documents that protein palmitoylation is a common modification in T. gondii that could have an impact on different cellular processes. PMID- 26825285 TI - Heart Team therapeutic decision-making and treatment in severe aortic valve stenosis. AB - Objectives After transcatheter aortic valve implantation (TAVI) has been available for high-risk patients with severe aortic valve stenosis (AVS), the decision-making of the Heart Team (HT) has not been examined. Design All adult patients with severe AVS referred to a large tertiary medical centre in 2011 were prospectively included. Multivariate regression analysis identified independent factors associated with treatment decisions. Results A total of 487 patients were included (mean age: 75 years, NYHA class III-IV: 47%). The HT proposed medical therapy (MT) in 35 (7%), TAVI in 60 (12%), and surgical aortic valve replacement (SAVR) in 392 (81%) of patients. In patients referred to intervention, TAVI compared with SAVR patients were older (OR = 1.17 per year, 95% CI 1.09-1.26; p < 0.01) with more previous coronary artery bypass surgery (OR = 385, 79-2738; p < 0.01), obesity (OR = 4.69, 1.51-13.77; p < 0.01), and chronic obstructive pulmonary disease (COPD) (OR = 3.66, 1.21-10.75; p = 0.02). MT patients compared with patients referred to any intervention were older, had a higher prevalence of COPD, peripheral arterial disease, previous myocardial infarction, and cerebrovascular disease. Conclusions The HT proposed intervention in 93% of patients with severe AVS despite high age, advanced symptoms and a high burden of co-morbidity. TAVI was reserved for older patients particularly with previous CABG. PMID- 26825286 TI - Mass spectrometry of oligopeptides in the presence of large amounts of alkali halides using desorption/ionization induced by neutral cluster impact. AB - Oligopeptides in the presence of large amounts of salt were desorbed and ionized using desorption/ionization induced by neutral clusters (DINeC) for further analysis by means of mass spectrometry (MS). Using oligopeptides in alkali halide solutions as a model system, DINeC was shown to yield clear and fragmentation free mass spectra of the biomolecules even from environments with a large excess of salt. The results were traced back to a phase separation between salt and biomolecules during sample preparation. The ratio between alkali metal complexes [M+A](+) and bare biomolecules [M+H](+) was controlled using different preparation schemes. DINeC was applied to the products of a tryptic digest of bovine serum albumin in the presence of sodium chloride; the results of a mass fingerprint analysis did not show a major difference for the spectra with and without salt in the original solution. The metal-ion/peptide interaction was further investigated by means of tandem-MS. PMID- 26825287 TI - Matrix effects in biological SIMS using cluster ion beams of different chemical composition. AB - The influence of the matrix effect on secondary ion yield presents a very significant challenge in quantitative secondary ion mass spectrometry (SIMS) analysis, for example, in determining the relative concentrations of metabolites that characterize normal biological activities or disease progression. Not only the sample itself but also the choice of primary ion beam may influence the extent of ionization suppression/enhancement due to the local chemical environment. In this study, an assessment of ionization matrix effects was carried out on model systems using C60 (+), Arn (+), and (H2O)n (+) cluster ion beams. The analytes are pure and binary mixtures of amino acids arginine and histidine biological standards. Ion beams of 20 keV were compared with a range of cluster sizes n = 1000-10 000. The component secondary ion yields were assessed for matrix effects using different primary ion beams and sample composition. The presence of water in the cluster beam is associated with a reduction in the observed matrix effects, suggesting that chemically reactive ion beams may provide a route to more quantitative SIMS analysis of complex biological systems. PMID- 26825288 TI - From home deliveries to health care facilities: establishing a traditional birth attendant referral program in Kenya. AB - OBJECTIVE: To assess the effectiveness of a traditional birth attendant (TBA) referral program on increasing the number of deliveries overseen by skilled birth attendants (SBA) in rural Kenyan health facilities before and after the implementation of a free maternity care policy. METHODS: In a rural region of Kenya, TBAs were recruited to educate pregnant women about the importance of delivering in healthcare facilities and were offered a stipend for every pregnant woman whom they brought to the healthcare facility. We evaluated the percentage of prenatal care (PNC) patients who delivered at the intervention site compared with the percentage of PNC patients who delivered at rural control facilities, before and after the referral program was implemented, and before and after the Kenya government implemented a policy of free maternity care. The window period of the study was from July of 2011 through September 2013, with a TBA referral intervention conducted from March to September 2013. RESULTS: The absolute increases from the pre-intervention period to the TBA referral intervention period in SBA deliveries were 5.7 and 24.0% in the control and intervention groups, respectively (p < 0.001). The absolute increases in SBA delivery rates from the pre-intervention period to the intervention period before the implementation of the free maternity care policy were 4.7 and 17.2% in the control and intervention groups, respectively (p < 0.001). After the policy implementation the absolute increases from pre-intervention to post-intervention were 1.8 and 11.6% in the control and intervention groups, respectively (p < 0.001). CONCLUSION: The percentage of SBA deliveries at the intervention health facility significantly increased compared to control health facilities when TBAs educated women about the need to deliver with a SBA and when TBAs received a stipend for bringing women to local health facilities to deliver. Furthermore, this TBA referral program proved to be far more effective in the target region of Kenya than a policy change to provide free obstetric care. PMID- 26825289 TI - Risk of Asthma from Cesarean Delivery Depends on Membrane Rupture. AB - OBJECTIVE: To assess our prospective mother-child cohort and the national registry data to analyze the risk of asthma by delivery mode and whether cesarean delivery before or after membrane rupture affects this risk differently. STUDY DESIGN: The Copenhagen Prospective Studies on Asthma in Childhood2000 is a high risk birth cohort of 411 Danish children. Asthma was diagnosed prospectively by physicians at the research site, and associations with cesarean delivery were investigated using Cox proportional hazard models. From the Danish national prospective registry we included data from 1997-2010. Childhood asthma was defined from recurrent use of inhaled corticosteroids filled at pharmacies. Cesarean delivery was classified as either before or after rupture of membranes, and the risk of asthma was compared with vaginal delivery. Results were adjusted stepwise for age and calendar year, sex, birth weight, gestational age, multiple births, parity, and maternal factors (age, smoking/antibiotics during pregnancy, employment status, and asthma). RESULTS: In the Copenhagen Prospective Studies on Asthma in Childhood2000 cohort, the adjusted hazard ratio for asthma was increased by cesarean delivery relative to vaginal birth 2.18 (1.27-3.73). Registry data replicated these findings. Cesarean delivery performed before rupture of membranes carried significantly higher risk of asthma, (incidence rate ratio to vaginal delivery 1.20 [1.16-1.23]) than cesarean delivery after rupture of membranes (incidence rate ratio to vaginal delivery 1.12 [1.09-1.16]). CONCLUSIONS: We confirmed cesarean delivery to be a risk factor for childhood asthma. This effect was more pronounced for cesarean delivery performed before rupture of membranes. PMID- 26825290 TI - Lethal Disorder of Mitochondrial Fission Caused by Mutations in DNM1L. AB - We describe two infants with hypotonia, absent respiratory effort, and giant mitochondria in neurons due to compound heterozygosity for 2 nonsense mutations of DNM1L. DNM1L has a critical role in regulating mitochondrial morphology and function. This observation confirms the central role of mitochondrial fission to normal human development. PMID- 26825291 TI - WD40-REPEAT 5a functions in drought stress tolerance by regulating nitric oxide accumulation in Arabidopsis. AB - Nitric oxide (NO) generation by NO synthase (NOS) in guard cells plays a vital role in stomatal closure for adaptive plant response to drought stress. However, the mechanism underlying the regulation of NOS activity in plants is unclear. Here, by screening yeast deletion mutants with decreased NO accumulation and NOS like activity when subjected to H2 O2 stress, we identified TUP1 as a novel regulator of NOS-like activity in yeast. Arabidopsis WD40-REPEAT 5a (WDR5a), a homolog of yeast TUP1, complemented H2 O2 -induced NO accumulation of a yeast mutant Deltatup1, suggesting the conserved role of WDR5a in regulating NO accumulation and NOS-like activity. This note was further confirmed by using an Arabidopsis RNAi line wdr5a-1 and two T-DNA insertion mutants of WDR5a with reduced WDR5a expression, in which both H2 O2 -induced NO accumulation and stomatal closure were repressed. This was because H2 O2 -induced NOS-like activity was inhibited in the mutants compared with that of the wild type. Furthermore, these wdr5a mutants were more sensitive to drought stress as they had reduced stomatal closure and decreased expression of drought-related genes. Together, our results revealed that WDR5a functions as a novel factor to modulate NOS-like activity for changes of NO accumulation and stomatal closure in drought stress tolerance. PMID- 26825292 TI - Non-motor and Extracerebellar Features in Spinocerebellar Ataxia Type 2. AB - Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant degenerative disease. Pathological studies have demonstrated not only cerebellar and brainstem atrophy, but substantia nigra, motoneurons, basal ganglia, thalamus, and peripheral nerves involvement. These findings may explain non-motor and extra cerebellar features in SCA2. We accessed the non-motor symptoms and extra cerebellar signs in SCA2 patients in order to provide a better understanding on pathophysiological mechanisms and natural history of brain degeneration in the disease. Thirty-three SCA2 patients were evaluated and compared with 26 healthy subjects. We investigated the following variables: sleep disorders, cognitive deficit, olfactory impairment, urinary dysfunction, psychiatric symptoms, cramps, pain, movement disorders, and weight loss. SCA2 had a high frequency of REM sleep behavior disorder (48.48 %, N = 16) as well as excessive daytime sleepiness (42.42 %, N = 14). Chorea was present in 15.15 % (N = 5), dystonia in 27.27 % (N = 9), and parkinsonism in 27.27 % (N = 9). Slow saccadic pursuit was present in 87.87 % (N = 29) and ophtalmoparesis in 78.78 % (N = 26) of patients. Regarding sleep disorders, 18.18 % (N = 6) of patients had restless leg syndrome. Dysphagia was present in 39.39 % (N = 13), weight loss 24.24 % (N = 8), and urinary dysfunction 27.27 % (N = 9). Cramps was present in only 6 % of patients (N = 2). This study highlighted the high frequency of non-motor symptoms and extra cerebellar signs in SCA2. Our findings demonstrate the widespread of nervous system involvement in SCA2 patients and contribute to better understand the natural history of brain degeneration in this genetic condition. PMID- 26825293 TI - Genomic and functional approaches reveal a case of adaptive introgression from Populus balsamifera (balsam poplar) in P. trichocarpa (black cottonwood). AB - Natural hybrid zones in forest trees provide systems to study the transfer of adaptive genetic variation by introgression. Previous landscape genomic studies in Populus trichocarpa, a keystone tree species, indicated genomic footprints of admixture with its sister species Populus balsamifera and identified candidate genes for local adaptation. Here, we explored the patterns of introgression and signals of local adaptation in P. trichocarpa and P. balsamifera, employing genome resequencing data from three chromosomes in pure species and admixed individuals from wild populations. Local ancestry analysis in admixed P. trichocarpa revealed a telomeric region in chromosome 15 with P. balsamifera ancestry, containing several candidate genes for local adaptation. Genomic analyses revealed signals of selection in certain genes in this region (e.g. PRR5, COMT1), and functional analyses based on gene expression variation and correlations with adaptive phenotypes suggest distinct functions of the introgressed alleles. In contrast, a block of genes in chromosome 12 paralogous to the introgressed region showed no signs of introgression or signatures of selection. We hypothesize that the introgressed region in chromosome 15 has introduced modular or cassette-like variation into P. trichocarpa. These linked adaptive mutations are associated with a block of genes in chromosome 15 that appear to have undergone neo- or subfunctionalization relative to paralogs in a duplicated region on chromosome 12 that show no signatures of adaptive variation. The association between P. balsamifera introgressed alleles with the expression of adaptive traits in P. trichocarpa supports the hypothesis that this is a case of adaptive introgression in an ecologically important foundation species. PMID- 26825294 TI - Spatial distribution of proteins in the quagga mussel adhesive apparatus. AB - The invasive freshwater mollusc Dreissena bugensis (quagga mussel) sticks to underwater surfaces via a proteinacious 'anchor' (byssus), consisting of a series of threads linked to adhesive plaques. This adhesion results in the biofouling of crucial underwater industry infrastructure, yet little is known about the proteins responsible for the adhesion. Here the identification of byssal proteins extracted from freshly secreted byssal material is described. Several new byssal proteins were observed by gel electrophoresis. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to characterize proteins in different regions of the byssus, particularly those localized to the adhesive interface. Byssal plaques and threads contain in common a range of low molecular weight proteins, while several proteins with higher mass were observed only in the plaque. At the adhesive interface, a plaque-specific ~8.1 kDa protein had a relative increase in signal intensity compared to the bulk of the plaque, suggesting it may play a direct role in adhesion. PMID- 26825295 TI - Anomalous left main coronary artery detected by CT angiography. AB - The growing improvements of computed tomography have made this technique more and more available for cardiac evaluation. Coronary artery anomalies (CAAs) are often incidental findings in subjects with suspected coronary artery disease (CAD) undergoing coronary angiography or computed tomography coronary angiography (CTCA). In some cases, CAAs can be clinically relevant so their identification could change radically patient management and treatment. We report the case of a 68-year-old male patient with known CAD and associated anomalous origination of the left coronary artery from the opposite sinus. PMID- 26825296 TI - What Do the Various Principles of Justice Mean Within the Concept of Benefit Sharing? AB - The concept of benefit sharing pertains to the act of giving something in return to the participants, communities, and the country that have participated in global health research or bioprospecting activities. One of the key concerns of benefit sharing is the ethical justifications or reasons to support the practice of the concept in global health research and bioprospecting. This article evaluates one of such ethical justifications and its meaning to benefit sharing, namely justice. We conducted a systematic review to map the various principles of justice that are linked to benefit sharing and analysed their meaning to the concept of benefit sharing. Five principles of justice (commutative, distributive, global, procedural, and compensatory) have been shown to be relevant in the nuances of benefit sharing in both global health research and bioprospecting. The review findings indicate that each of these principles of justice provides a different perspective for a different benefit sharing rationale. For example, commutative justice provides a benefit sharing rationale that is focused on fair exchange of benefits between research sponsors and communities. Distributive justice produces a benefit sharing rationale that is focused on improving the health needs of the vulnerable research communities. We have suggested that a good benefit sharing framework particularly in global health research would be more beneficial if it combines all the principles of justice in its formulation. Nonetheless, there is a need for empirical studies to examine the various principles of justice and their nuances in benefit sharing among stakeholders in global health research. PMID- 26825297 TI - A green synthesis in water of novel (1,5,3-dithiazepan-3-yl)alkanoic acids by the multicomponent reaction of amino acids, CH2O, and 1,2-ethanedithiol. AB - A library of new (1,5,3-dithiazepan-3-yl)alkanoic acids was prepared by the multicomponent cyclocondensation of amino acids, formaldehyde, and 1,2 ethanedithiol in water at room temperature for 1 to 5 h in high yields. This green procedure offers several advantages such as an operational simplicity, no catalyst, and no production of hazardous materials. PMID- 26825298 TI - Monitoring free-living Japanese Bush Warblers (Cettia diphone) in a most highly radiocontaminated area of Fukushima Prefecture, Japan. AB - The Fukushima-Daiichi Nuclear Power Plant (F1NPP) accident is an IAEA level 7 event, the same as that of Chernobyl, while the amount of radionuclides released is not comparable. Radioactivity attributed to the F1NPP accident was detected 250 km away from the F1NPP. Although we have not yet systematically studied the effect of radionuclides on the environment and wildlife, one of three Japanese Bush Warblers (Cettia diphone), captured in Akaugi district in August 2011, was observed to have a conspicuous lesion near the cloaca, which is rare in Japan. All of the birds' feathers were strongly contaminated. Further study is needed to determine the significance of this result. We emphasize the importance of continuing assessment of the effects of the F1NPP accident on wildlife. PMID- 26825299 TI - Fukushima simulation experiment: assessing the effects of chronic low-dose-rate internal 137Cs radiation exposure on litter size, sex ratio, and biokinetics in mice. AB - To investigate the transgenerational effects of chronic low-dose-rate internal radiation exposure after the Fukushima Daiichi Nuclear Power Plant accident in Japan, 18 generations of mice were maintained in a radioisotope facility, with free access to drinking water containing (137)CsCl (0 and 100 Bq/ml). The (137)Cs distribution in the organs of the mice was measured after long-term ad libitum intake of the (137)CsCl water. The litter size and the sex ratio of the group ingesting the (137)Cs water were compared with those of the control group, for all 18 generations of mice. No significant difference was noted in the litter size or the sex ratio between the mice in the control group and those in the group ingesting the (137)Cs water. The fixed internal exposure doses were ~160 Bq/g and 80 Bq/g in the muscles and other organs, respectively. PMID- 26825300 TI - Electron probe X-ray microanalysis of boar and inobuta testes after the Fukushima accident. AB - We aimed to investigate the effect of chronic radiation exposure associated with the Fukushima Daiichi Nuclear Power Plant (FNPP) accident on the testes of boar and inobuta (a hybrid of Sus scrofa and Sus scrofa domestica). This study examined the contamination levels of radioactive caesium (Cs), especially (134)Cs and (137)Cs, in the testis of both boar and inobuta during 2012, after the Fukushima accident. Morphological analysis and electron-probe X-ray microanalysis (EPMA) were also undertaken on the testes. The (134)Cs and (137)Cs levels were 6430 +/- 23 and 6820 +/- 32 Bq/kg in the boar testes, and 755 +/- 13 and 747 +/- 17 Bq/kg in the inobuta testes, respectively. The internal and external exposure of total (134)Cs and (137)Cs in the boar testes were 47.1 mGy and 176.2 mGy, respectively, whereas in the inobuta testes, these levels were 6.09 mGy and 59.8 mGy, respectively. Defective spermatogenesis was not detected by the histochemical analysis of radiation-exposed testes for either animal. In neither animal were Cs molecules detected, using EPMA. In conclusion, we showed that adverse radiation-induced effects were not detected in the examined boar and inobuta testes following the chronic radiation exposure associated with the FNPP accident. PMID- 26825301 TI - Hereditary effects of radioactive fallout on gall-forming aphids and the subsequent recovery process near the Fukushima Daiichi Nuclear Power Plant. PMID- 26825302 TI - Monitoring of avian productivity and tail feathers. PMID- 26825303 TI - Protective activity of kudzu (Pueraria thunbergiana) vine on chemically-induced hepatotoxicity: in vitro and in vivo studies. AB - BACKGROUND: Kudzu (Pueraria thunbergiana) root has long been used in Traditional Chinese Medicine. However, the vine of the kudzu plant has been considered waste material. This study aimed to investigate the hepatoprotective properties of the kudzu vine. METHODS: We created 0 %, 30 %, 70 %, and 95 % ethanolic kudzu vine extracts. The isoflavone contents of kudzu vine extract were quantified by high performance liquid chromatography. Tertiary-butylhydroperoxide (t-BHP) was added to human liver-derived HepG2 cells, and the production of reactive oxygen species was measured in the presence and absence of kudzu vine extract. Antioxidant activity was evaluated in all kudzu vine extracts using a hydroxyradical scavenging assay. Thirty-five male Sprague-Dawley rats were divided into seven groups (n = 5); two groups were not given any extract or drug, one group was treated with 50 mg/kg silymarin orally for 5 days, and the remaining four groups were respectively treated with 100 mg/kg of 0%, 30%, 70%, or 95% ethanolic extract of kudzu vine orally once daily for 5 days. On day 5 the treatment groups and one untreated group were fed 0.75 ml/kg carbon tetrachloride (CCl4) to induce liver damage. Blood and liver tissue samples were collected 24 h after CCl4 administration for measurement of plasma alanine aminotransferase and aspartate aminotransferase, and concentration of malondialdehyde and glutathione in liver tissue. RESULTS: Puerarin was the most abundant isoflavone in kudzu vine extract. Kudzu vine extract significantly reduced the cytotoxicity and production of reactive oxygen species induced by t-BHP in a dose-dependent manner. Treatment with 0 % and 30 % ethanolic extracts of kudzu vine significantly lowered the plasma levels of alanine aminotransferase and aspartate aminotransferase in a CCl4-induced hepatotoxicity rat model (P < 0.05). Glutathione was significantly elevated in the 30 % ethanolic extract-treated group (P < 0.05), while the malondialdehyde level in liver tissue was significantly decreased in the 0 % and 30 % ethanolic extract-treated groups (P < 0.05). CONCLUSIONS: The kudzu vine is potentially highly beneficial in treating liver damage, as it scavenges reactive free radicals and boosts the endogenous antioxidant system. PMID- 26825304 TI - Functional polymorphisms in the P2X7 receptor gene are associated with stress fracture injury. AB - Military recruits and elite athletes are susceptible to stress fracture injuries. Genetic predisposition has been postulated to have a role in their development. The P2X7 receptor (P2X7R) gene, a key regulator of bone remodelling, is a genetic candidate that may contribute to stress fracture predisposition. The aim of this study is to evaluate the putative contribution of P2X7R to stress fracture injury in two separate cohorts, military personnel and elite athletes. In 210 Israeli Defense Forces (IDF) military conscripts, stress fracture injury was diagnosed (n = 43) based on symptoms and a positive bone scan. In a separate cohort of 518 elite athletes, self-reported medical imaging scan-certified stress fracture injuries were recorded (n = 125). Non-stress fracture controls were identified from these cohorts who had a normal bone scan or no history or symptoms of stress fracture injury. Study participants were genotyped for functional SNPs within the P2X7R gene using proprietary fluorescence-based competitive allele-specific PCR assay. Pearson's chi-squared (chi (2)) tests, corrected for multiple comparisons, were used to assess associations in genotype frequencies. The variant allele of P2X7R SNP rs3751143 (Glu496Ala-loss of function) was associated with stress fracture injury, whilst the variant allele of rs1718119 (Ala348Thr-gain of function) was associated with a reduced occurrence of stress fracture injury in military conscripts (P < 0.05). The association of the variant allele of rs3751143 with stress fractures was replicated in elite athletes (P < 0.05), whereas the variant allele of rs1718119 was also associated with reduced multiple stress fracture cases in elite athletes (P < 0.05). The association between independent P2X7R polymorphisms with stress fracture prevalence supports the role of a genetic predisposition in the development of stress fracture injury. PMID- 26825306 TI - Erratum to: Beneficial reward-to-risk action of glucosamine during pathogenesis of osteoarthritis. PMID- 26825305 TI - Inter-subunit disulfide locking of the human P2X3 receptor elucidates ectodomain movements associated with channel gating. AB - P2X3 receptors (P2X3R) are trimeric ATP-gated cation channels involved in sensory neurotransmission and inflammatory pain. We used homology modeling and molecular dynamic simulations of the hP2X3R to identify inter-subunit interactions of residues that are instrumental to elucidate conformational changes associated with gating of the hPX3R. We identified an ionic interaction between E112 and R198 of the head domain and dorsal fin domain, respectively, and E57 and T263 of the lower body domains of adjacent subunits and detected a marked rearrangement of these domains during gating of the hP3X3R. Double-mutant cycle analysis of the inter-subunit residue pairs E112/R198 and E57/T263 revealed significant interaction-free energies. Disulfide locking of the hP2X3R E112C/R198C or the E57C/T263C double cysteine mutants markedly reduced the ATP-induced current responses. The decreased current amplitude following inter-subunit disulfide cross-linking indicates that disulfide locking of the head and dorsal fin domains or at the level of the lower body domains of the hP2X3R prevents the gating induced conformational rearrangement of the subunits with respect to each other. The distinct reorganization of the subunit interfaces during gating of the hP2X3R is generally consistent with the gating mechanism of other P2XRs. Charge-reversal mutagenesis and methanethiosulfonate (MTS)-modification of substituted cysteines demonstrated that E112 and R198 interact electrostatically. Both disulfide locking and salt bridge breaking of the E112/R198 interaction reduced the hP2X3R function. We conclude that the inter-subunit salt bridge between E112 and R198 of the head and dorsal fin domains, respectively, serves to control the mobility of these domains during agonist-activation of the hP2X3R. PMID- 26825307 TI - Resolution of diarrhea in an immunocompromised patient with chronic norovirus gastroenteritis correlates with constitution of specific antibody blockade titer. AB - Norovirus gastroenteritis in immunocompromised hosts can result in a serious and prolonged diarrheal illness. We present a case of chronic norovirus disease during rituximab-bendamustine chemotherapy for non-Hodgkin's lymphoma. We show for the first time a correlation between norovirus strain-specific antibody blockade titers and symptom improvement in an immunocompromised host. PMID- 26825308 TI - Listeria meningoencephalitis and anti-GQ1b antibody syndrome. AB - We report the first case of Listeria monocytogenes meningoencephalitis associated with anti-GQ1b antibody syndrome in an immunocompetent adult. A prompt diagnosis, made thanks to the multidisciplinary contribution, allowed a combined therapeutic approach leading to final favourable outcome, despite several intercurrent complications. PMID- 26825309 TI - Using the Gene Ontology to Annotate Key Players in Parkinson's Disease. AB - The Gene Ontology (GO) is widely recognised as the gold standard bioinformatics resource for summarizing functional knowledge of gene products in a consistent and computable, information-rich language. GO describes cellular and organismal processes across all species, yet until now there has been a considerable gene annotation deficit within the neurological and immunological domains, both of which are relevant to Parkinson's disease. Here we introduce the Parkinson's disease GO Annotation Project, funded by Parkinson's UK and supported by the GO Consortium, which is addressing this deficit by providing GO annotation to Parkinson's-relevant human gene products, principally through expert literature curation. We discuss the steps taken to prioritise proteins, publications and cellular processes for annotation, examples of how GO annotations capture Parkinson's-relevant information, and the advantages that a topic-focused annotation approach offers to users. Building on the existing GO resource, this project collates a vast amount of Parkinson's-relevant literature into a set of high-quality annotations to be utilized by the research community. PMID- 26825310 TI - Combined effect of unsaturated fatty acids and saturated fatty acids on the metabolic syndrome: Tehran lipid and glucose study. AB - AIMS: The aim of this study was to investigate whether the background intakes of total dietary fat, monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) modulate the effects of dietary saturated fatty acids (SFA) on metabolic syndrome (MetS). MATERIAL AND METHODS: This population-based cross sectional study was conducted on a representative sample of 4,677 adults, aged 19 to 84 years. MetS was defined according to the ATP III criteria. RESULTS: Median intakes of SFA, MUFA and PUFA were 9.5, 9.6 and 5.6% of total energy. High SFA intakes were associated with higher prevalence of MetS, in both individuals with higher and lower median intakes of total fat, MUFA and PUFA. CONCLUSIONS: Our findings indicate that SFA intakes were positively associated with the prevalence of MetS, independent of total dietary fat, MUFA and PUFA intake. PMID- 26825311 TI - Evaluation of a smartphone camera system to enable visualization and image transmission to aid tracheal intubation with the Airtraq((r)) laryngoscope. AB - Using three-dimensional printing, we produced adaptors to attach a smartphone with camera to the eyepiece of the Airtraq((r)) laryngoscope. This low-cost system enabled a team to simultaneously view the laryngoscopy process on the smartphone screen, and also enabled image transmission. We compared the Airtraq((r)) with the smartphone Airtraq((r)) system in a crossover study of trainee anesthesiologists performing tracheal intubation in a manikin. We also evaluated the smartphone Airtraq((r)) system for laryngoscopy and tracheal intubation in 30 patients, including image transmission to and communication with a remote instructor. In the manikin study, the smartphone Airtraq((r)) system enabled instruction where both trainee and instructor could view the larynx simultaneously, and did not substantially increase the time required for intubation. In the patient study, we were able to view the larynx in all 30 patients, and the remote instructor was able to receive the images and to respond on correctness of laryngoscopy and tracheal tube placement. Tracheal intubation was successful within 90s in 19 (63 %) patients. In conclusion, use of a smartphone with the Airtraq((r)) may facilitate instruction and communication of laryngoscopy with the Airtraq((r)), overcoming some of its limitations. PMID- 26825314 TI - Top US cancer centers push for more use of HPV vaccine. PMID- 26825313 TI - Vaccination control programs for multiple livestock host species: an age stratified, seasonal transmission model for brucellosis control in endemic settings. AB - BACKGROUND: Brucella melitensis causes production losses in ruminants and febrile disease in humans in Africa, Central Asia, the Middle East and elsewhere. Although traditionally understood to affect primarily sheep and goats, it is also the predominant Brucella species that affects cows in some endemic areas. Despite this, no licensed vaccine is available specifically for use against B. melitensis in cows. The mainstay of most control programs is vaccination of sheep and goats with a live vaccine, Rev-1. The aim of this study was to investigate how critical vaccination of cows might be, in order to control B. melitensis on a mixed sheep and-cattle farm. METHODS: A dynamic, differential-equation, age-structured, seasonal model with births and deaths, was used to investigate whether vaccination of both sheep and cattle had an impact on time to elimination of brucellosis on an individual mixed species farm, when compared to vaccination of sheep only. The model was a Susceptible-Exposed-Infectious-Recovered-Susceptible (SEIRS) model with an additional compartment for Persistently Infected (PI) individuals. Transmission parameters were fit based on a nation-wide probabilistic seroprevalence survey in Jordan. RESULTS: The model predicted that it would take 3.5 years to eliminate brucellosis (to less than 0.5% of adult sheep seropositive as a result of infection) on a mixed-species B. melitensis endemic farm with the median field-study seroprevalence, following vaccination of both sheep and cattle, assuming a vaccine effectiveness of 80%. Limiting the vaccination to sheep only, increased the time to 16.8 years. Sensitivity analysis showed that the finding that vaccination of cattle was of significant importance, was robust. Vaccine effectiveness had a strong influence on time to elimination. CONCLUSIONS: In the absence of further data, vaccination of cattle should be considered essential in Brucella-endemic settings where mixed small ruminant and cattle flocks predominate. Further evidence that Brucella melitensis predominates in cattle in Jordan, as opposed to Brucella abortus, is needed in order to validate this model. The results may be applicable to other mixed-species settings with similar livestock management practices. These methods may be applied to other pathogens affecting multiple livestock species or with seasonal transmission. PMID- 26825312 TI - Minocycline Transiently Reduces Microglia/Macrophage Activation but Exacerbates Cognitive Deficits Following Repetitive Traumatic Brain Injury in the Neonatal Rat. AB - Elevated microglial/macrophage-associated biomarkers in the cerebrospinal fluid of infant victims of abusive head trauma (AHT) suggest that these cells play a role in the pathophysiology of the injury. In a model of AHT in 11-day-old rats, 3 impacts (24 hours apart) resulted in spatial learning and memory deficits and increased brain microglial/macrophage reactivity, traumatic axonal injury, neuronal degeneration, and cortical and white-matter atrophy. The antibiotic minocycline has been effective in decreasing injury-induced microglial/macrophage activation while simultaneously attenuating cellular and functional deficits in models of neonatal hypoxic ischemia, but the potential for this compound to rescue deficits after impact-based trauma to the immature brain remains unexplored. Acute minocycline administration in this model of AHT decreased microglial/macrophage reactivity in the corpus callosum of brain-injured animals at 3 days postinjury, but this effect was lost by 7 days postinjury. Additionally, minocycline treatment had no effect on traumatic axonal injury, neurodegeneration, tissue atrophy, or spatial learning deficits. Interestingly, minocycline-treated animals demonstrated exacerbated injury-induced spatial memory deficits. These results contrast with previous findings in other models of brain injury and suggest that minocycline is ineffective in reducing microglial/macrophage activation and ameliorating injury-induced deficits following repetitive neonatal traumatic brain injury. PMID- 26825315 TI - Management of septic shock and severe infections in migrants and returning travelers requiring critical care. AB - During the past decade, global human movement created a virtually "borderless world". Consequently, the developed world is facing "forgotten" and now imported infectious diseases. Many infections are observed upon travel and migration, and the clinical spectrum is diverse, ranging from asymptomatic infection to severe septic shock. The severity of infection depends on the etiology and timeliness of diagnosis. While assessing the etiology of severe infection in travelers and migrants, it is important to acquire a detailed clinical history; geography, dates of travel, places visited, type of transportation, lay-overs and intermediate stops, potential exposure to exotic diseases, and activities that were undertaken during travelling and prophylaxis and vaccines either taken or not before travel are all important parameters. Tuberculosis, malaria, pneumonia, visceral leishmaniasis, enteric fever and hemorrhagic fever are the most common etiologies in severely infected travelers and migrants. The management of severe sepsis and septic shock in migrants and returning travelers requires a systematic approach in the evaluation of these patients based on travel history. Early and broad-spectrum therapy is recommended for the management of septic shock comprising broad spectrum antibiotics, source control, fluid therapy and hemodynamic support, corticosteroids, tight glycemic control, and organ support and monitoring. We here review the diagnostic and therapeutic routing of severely ill travelers and migrants, stratified by the nature of the infectious agents most often encountered among them. PMID- 26825316 TI - Time to positivity of blood culture and its prognostic value in bloodstream infection. AB - The purpose of this study was to investigate the relationship between the time to positivity (TTP) of blood cultures and outcome in patients with bloodstream infections (BSIs). Between January 1st, 2011 and December 31st, 2013, the blood cultures of inpatients with BSI or catheter-related BSI were collected at Peking University Third Hospital. The TTP of different isolates was analyzed, and the relationship between the TTP of isolates and outcome of patients with Enterobacter BSI was retrospectively analyzed. We analyzed the TTP of 886 isolates. Escherichia coli has the shortest (11.97 +/- 10.06 h) and Candida has the longest first TTP (61.62 +/- 42.77 h). 68.01 % of isolates reached positivity within 24 h and 88.33 % within 48 h. Over 90 % of E. coli isolates reached positivity within 24 h. Over 50 % of Candida isolates reached positivity within 48 h. The TTP differed significantly between cultures that were single or double positive for coagulase-negative staphylococci isolates, Enterobacteriaceae, and Pseudomonas aeruginosa, and between aerobic and anaerobic cultures of E. coli (p < 0.05). However, the TTP did not differ significantly between coagulase-negative staphylococci (double positivity) and Staphylococcus aureus. The best TTP threshold for prediction of mortality from Enterobacter species BSI was 16.3 h [area under the curve (AUC) 0.730, 95 % confidence interval (CI) 0.557, 0.864, sensitivity 100 %, specificity 44.4 %]. The TTP of clinical isolates may represent a valuable marker of the clinical significance of BSIs. Laboratories and clinics should consider using the TTP to predict the prognosis of patients with BSI by bacteria, including Enterobacter and other species. PMID- 26825317 TI - Pathobiological mechanisms of peritoneal adhesions: The mesenchymal transition of rat peritoneal mesothelial cells induced by TGF-beta1 and IL-6 requires activation of Erk1/2 and Smad2 linker region phosphorylation. AB - Peritoneal adhesions, primarily caused by surgical procedures, are the leading cause of pelvic pain, bowel obstruction, and infertility. TGF-beta1 and IL-6 have been found to be elevated in the peritoneal fluid of patients during/after abdominal surgery. However, it remains to be determined whether these cytokines interact and facilitate adhesion formation by promoting mesothelial to mesenchymal transition (MMT). In the present study, isolated rat peritoneal mesothelial cells were treated with TGF-beta1 and/or IL-6 which elicited MMT as determined by morphologic and biochemical techniques. During this transition, cellular morphology changed from that of cobblestone polygonal cells to elongated/spindle-shaped fibroblast-like cells. There was decreased expression of genes characteristic of mesothelial cells, such as E-cadherin, and increased expression of genes characteristic of the myofibroblast phenotype, including alpha-smooth muscle actin and the EDA form of fibronectin, both of which appear to mediate the transfer of force to the extracellular matrix. Partial characterization of relevant signaling pathways identified Erk1/2 activation, which was enhanced by combined TGF-beta1/IL-6 administration, as a crucial necessary factor in the transition. Erk1/2 activation as well as the phosphorylation of the linker region of Smad2 and MMT could be blocked by the MEK inhibitor, U0126, suggesting that such activation may be a potential pharmaceutical target to prevent MMT. In addition, the phenotypic transition could be prevented by hydrocortisone. PMID- 26825318 TI - Tendon mineralization is progressive and associated with deterioration of tendon biomechanical properties, and requires BMP-Smad signaling in the mouse Achilles tendon injury model. AB - Ectopic tendon mineralization can develop following tendon rupture or trauma surgery. The pathogenesis of ectopic tendon mineralization and its clinical impact have not been fully elucidated yet. In this study, we utilized a mouse Achilles tendon injury model to determine whether ectopic tendon mineralization alters the biomechanical properties of the tendon and whether BMP signaling is involved in this condition. A complete transverse incision was made at the midpoint of the right Achilles tendon in 8-week-old CD1 mice and the gap was left open. Ectopic cartilaginous mass formation was found in the injured tendon by 4weeks post-surgery and ectopic mineralization was detected at 8 to 10weeks post surgery. Ectopic mineralization grew over time and volume of the mineralized materials of 25-weeks samples was about 2.5 fold bigger than that of 10-weeks samples, indicating that injury-induced ectopic tendon mineralization is progressive. In vitro mechanical testing showed that max force, max stress and mid-substance modulus in the 25-weeks samples were significantly lower than the 10-weeks samples. We observed substantial increases in expression of bone morphogenetic protein family genes in injured tendons 1week post-surgery. Immunohistochemical analysis showed that phosphorylation of both Smad1 and Smad3 was highly increased in injured tendons as early as 1week post-injury and remained high in ectopic chondrogenic lesions 4-weeks post-injury. Treatment with the BMP receptor kinase inhibitor (LDN193189) significantly inhibited injury induced tendon mineralization. These findings indicate that injury-induced ectopic tendon mineralization is progressive, involves BMP signaling and associated with deterioration of tendon biomechanical properties. PMID- 26825319 TI - The World Hip Trauma Evaluation Study 3: Hemiarthroplasty Evaluation by Multicentre Investigation - WHITE 3: HEMI - An Abridged Protocol. AB - BACKGROUND: Approximately half of all hip fractures are displaced intracapsular fractures. The standard treatment for these fractures is either hemiarthroplasty or total hip arthroplasty. The recent National Institute for Health and Care Excellence (NICE) guidance on hip fracture management recommends the use of 'proven' cemented stem arthroplasty with an Orthopaedic Device Evaluation Panel (ODEP) rating of at least 3B (97% survival at three years). The Thompsons prosthesis is currently lacking an ODEP rating despite over 50 years of clinical use, likely due to the paucity of implant survival data. Nationally, adherence to these guidelines is varied as there is debate as to which prosthesis optimises patient outcomes. DESIGN: This study design is a multi-centre, multi-surgeon, parallel, two arm, standard-of-care pragmatic randomised controlled trial. It will be embedded within the WHiTE Comprehensive Cohort Study (ISRCTN63982700). The main analysis is a two-way equivalence comparison between Hemi-Thompson and Hemi-Exeter polished taper with Unitrax head. Secondary outcomes will include radiological leg length discrepancy measured as per Bidwai and Willett, mortality, re-operation rate and indication for re-operation, length of index hospital stay and revision at four months. This study will be supplemented by the NHFD (National Hip Fracture Database) dataset. DISCUSSION: Evidence on the optimum choice of prosthesis for hemiarthroplasty of the hip is lacking. National guidance is currently based on expert opinion rather than empirical evidence. The incidence of hip fracture is likely to continue to increase and providing high quality evidence on the optimumCite this article: A. L. Sims. The World Hip Trauma Evaluation Study 3: Hemiarthroplasty Evaluation by Multicentre Investigation - WHITE 3: HEMI - An Abridged Protocol. Bone Joint Res 2016;5:18 25. doi: 10.1302/2046-3758.51.2000473. PMID- 26825320 TI - Water use practices, water quality, and households' diarrheal encounters in communities along the Boro-Thamalakane-Boteti river system, Northern Botswana. AB - BACKGROUND: Some rural African communities residing along rivers use the untreated river water for domestic purposes, making them vulnerable to waterborne diseases such as diarrhea. METHODS: We determined water use practices and water quality, relating them to prevalence of diarrhea in communities along the Boro Thamalakane-Boteti river system, northern Botswana. A total of 452 households were interviewed and 196 water samples collected show during February, May, September, and December 2012 in settlements of Boro, Maun, Xobe, Samedupi, Chanoga, and Motopi. Information was sought on water use practices (collection, storage, and handling) and diarrheal experience using questionnaires. Water quality was assessed for physicochemical and microbiological parameters using portable field meters and laboratory analysis, respectively. RESULTS: All (100%) of the river water samples collected were fecally contaminated and unsuitable for domestic use without prior treatment. Samples had Escherichia coli (E.coli) and fecal streptococci levels reaching up to 186 and 140 CFU/100 ml, respectively. Study revealed high dependence on the fecally contaminated river water with low uptake of water treatment techniques. Up to 48% of households indicated that they experience diarrhea, with most cases occurring during the early flooding season (May). Nonetheless, there was no significant relationship between river water quality and households' diarrheal experience across studied settlements (p > 0.05). Failure to treat river water before use was a significant predictor of diarrhea (p = 0.028). CONCLUSIONS: Even though the river water was unsafe for domestic use, results imply further recontamination of water at household level highlighting the need for simple and affordable household water treatment techniques. PMID- 26825321 TI - Cardiac amyloidosis: an unusual cause of low flow-low gradient aortic stenosis with preserved ejection fraction. PMID- 26825322 TI - Developmental bias for number words in the intraparietal sulcus. AB - Children and adults show behavioral evidence of psychological overlap between their early, non-symbolic numerical concepts and their later-developing symbolic numerical concepts. An open question is to what extent the common cognitive signatures observed between different numerical notations are coupled with physical overlap in neural processes. We show that from 8 years of age, regions of the intraparietal sulcus (IPS) that exhibit a numerical ratio effect during non-symbolic numerical judgments also show a semantic distance effect for symbolic number words. In both children and adults, the IPS showed a semantic distance effect during magnitude judgments of number words (i.e. larger/smaller number) but not for magnitude judgments of object words (i.e. larger/smaller object size). The results provide novel evidence of conceptual overlap between neural representations of symbolic and non-symbolic numerical values that cannot be explained by a general process, and present the first demonstration of an early-developing dissociation between number words and object words in the human brain. PMID- 26825323 TI - Magnetically actuated microstructured surfaces can actively modify cell migration behaviour. AB - We present a study on the application of magnetically actuated polymer micropillar surfaces in modifying the migration behaviour of cells. We show that micropillar surfaces actuated at a frequency of 1 Hz can cause more than a 5-fold decrease in cell migration rates compared to controls, whereas non-actuated micropillar surfaces cause no statistically significant alterations in cell migration rates. The effectiveness of the micropillar arrays in impeding cell migration depends on micropillar density and placement patterns, as well as the direction of micropillar actuation with respect to the direction of cell migration. Since the magnetic micropillar surfaces presented can be actuated remotely with small external magnetic fields, their integration with implants could provide new possibilities for in-vivo tissue engineering applications. PMID- 26825324 TI - Journal of health, population and nutrition: celebrating an exciting new phase. PMID- 26825325 TI - Drug Prescribing Pattern During Intranatal Period in a Secondary Care Hospital in South India: A Retrospective Study. AB - BACKGROUND: During delivery, drugs being prescribed cause concerns due to their harmful effects on lactation as well as potential adverse reactions on the mother. This retrospective study was performed to evaluate the drug prescribing pattern during normal delivery in a secondary care hospital in India. MATERIALS AND METHODS: This cross-sectional retrospective study included 3 months of patient's medical records. RESULTS: A total of 2222 drugs, comprising 51 different types of drugs were prescribed to 313 mothers undergoing normal delivery. Most of these drugs are safe in lactation. Ten types of drugs would have been better avoided, but they possibly did not cause harm because of their limited short-term use only during the intranatal period. CONCLUSION: This study reflects a good, safe, and rational medication practice during normal delivery for various common ailments in a secondary care hospital and can be cited as an example for similar settings. PMID- 26825326 TI - Construction of the influenza A virus transmission tree in a college-based population: co-transmission and interactions between influenza A viruses. AB - BACKGROUND: Co-infection of different influenza A viruses is known to occur but how viruses interact within co-infection remains unknown. An outbreak in a college campus during the 2009 pandemic involved two subtypes of influenza A: persons infected with pandemic A/H1N1; persons infected with seasonal A/H3N2 viruses; and persons infected with both at the same time (co-infection). This provides data to analyse the possible interaction between influenza A viruses within co-infection. METHODS: We extend a statistical inference method designed for outbreaks caused by one virus to that caused by two viruses. The method uses knowledge of which subtype each case is infected with (and whether they were co infected), contact information and symptom onset date of each case in the influenza outbreak. We then apply it to construct the most likely transmission tree during the outbreak in the college campus. RESULTS: Analysis of the constructed transmission tree shows that the simultaneous presence of the two influenza viruses increases the infectivity and the transmissibility of A/H1N1 virus but whether it changes the infectivity of A/H3N2 is unclear. The estimation also shows that co-transmission of both subtypes from co-infection is low and therefore co-infection cannot be sustained on its own. CONCLUSIONS: This study suggests that influenza A viruses within co-infected patients can interact in some ways rather than transmit independently, and this can enhance the spread of influenza A virus infection. PMID- 26825327 TI - Phase I clinical trial of lenalidomide in combination with 5-fluorouracil, leucovorin, and oxaliplatin in patients with advanced cancer. AB - PURPOSE: Lenalidomide has synergistic anticancer effects when used with chemotherapy. We conducted a phase I study of lenalidomide in combination with FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) in patients with advanced cancer. METHODS: A "3 + 3" study design was used. Lenalidomide was given orally on days 1-14, oxaliplatin and leucovorin were given intravenously on day 1, and 5 fluorouracil was given as a continuous infusion on days 1-2. The dose escalation phase of the study was followed by an expansion phase. We assessed the maximum tolerated dose, dose-limiting toxicities, and response. RESULTS: Thirty-eight patients were treated [median age 53 years (range 31-76); male/female 20:18]. The most common diagnosis was colorectal cancer (CRC) (n= 30, 79%). Overall, 132 cycles (median 2/patient) were administered. No dose-limiting toxicities were observed. The maximum tested dose (dose level 4) was used in the expansion phase. Grade 3/4 treatment-related toxicities (all reversible) were seen in 14 (37%) patients and included neutropenia (n = 11), thrombocytopenia (n = 2), and fatigue (n = 2). There were no thrombotic events. Response was evaluable in 32 patients: 19 (59%) had stable disease (SD), including SD >= 6 months in 4 (13%) patients. Tumor types with SD >= 6 months were CRC (n = 2; progression-free survival [PFS] 11.3 and 7.1 months, respectively), gastric (n = 1; PFS 8.5 months), and pancreatic (n = 1; PFS 6.4 months) cancer. The median PFS and overall survival durations were 2.2 months (range <1.3-23) and 5.5 months (range <1.6-23), respectively. CONCLUSIONS: Lenalidomide in combination with FOLFOX was well tolerated. Four patients had prolonged stable disease. This combination merits further investigation for selected patient populations. PMID- 26825329 TI - Bidirectional association between atrial fibrillation and congestive heart failure in the elderly. AB - AIMS: The aim of this study was to examine the bidirectional association between atrial fibrillation and congestive heart failure (CHF) in older adults. METHODS: We studied the association of atrial fibrillation at entry with incident CHF (N = 5281; 85% white, 42% male) and the association of CHF at entry with incident atrial fibrillation (N = 5233; 85% white, 42% male) in the Cardiovascular Health Study (CHS). Baseline atrial fibrillation was identified during the study electrocardiogram and by self-reported history, and incident cases were identified during subsequent study electrocardiograms and hospitalization data. Baseline CHF was identified by self-reported history and adjudication of medical records, and incident cases were identified using hospitalization data. Cox regression was used to compute hazard ratios and 95% confidence intervals (CIs) for the association between atrial fibrillation and incident CHF, and CHF and incident atrial fibrillation, separately. RESULTS: Over a median follow-up of 12.6 years, 534 (10%) participants developed atrial fibrillation. CHF was associated with an increased risk of atrial fibrillation (hazard ratio 2.0, 95% CI 1.4, 3.0). A total of 1692 (32%) participants developed CHF over a median follow-up of 11.7 years and atrial fibrillation was associated with an increased risk of CHF (hazard ratio 1.9, 95% CI 1.5, 2.2). CONCLUSION: Our results suggest that a bidirectional relationship exists between atrial fibrillation and CHF, with each condition influencing the development of the other. PMID- 26825328 TI - Electromagnetic interference in implantable cardioverter defibrillators: present but rare. AB - PURPOSE: Electromagnetic interference (EMI) with implantable cardioverter defibrillators (ICDs) can cause oversensing and subsequently inappropriate ICD therapies. We retrospectively investigated the current incidence and clinical relevance of oversensing related EMI in a large cohort of ICD patients. METHODS: From January 2005 to April 2013, all ICD interrogations performed at our institution were analyzed for the occurrence of oversensing related EMI. EMI episodes were classified as clinically significant, potentially significant or of minor significance. To identify risk factors for EMI, we also analyzed different lead models in our cohort (integrated vs true bipolar leads). RESULTS: Data of 2940 ICD patients (mean age 63 +/- 16 years, 2322 male patients, 7772 patient years) were retrospectively analyzed for the occurrence of EMI. During the observation period, a total of 145 (hospital environment n = 97, non-hospital environment n = 48) episodes occurred and resulted in an overall EMI incidence, i.e. event rate, of 1.87 % per patient per year. Focusing on clinically significant or potentially significant episodes, the EMI incidence was 0.27 % per patient per year. Cox proportional hazards regression analysis did not reveal a statistically significant higher hazard of oversensing for patients with integrated bipolar leads compared to patients with true bipolar leads (HR = 2.21; 95 % CI 0.90-5.39; p = 0.083). CONCLUSIONS: Our data demonstrate that EMI continues to occur in everyday life. Patients should be well informed about the potential sources and risks of EMI but they need not be overly concerned since the risk of EMI-especially in a non-hospital environment-is low. PMID- 26825330 TI - Left ventricular mechanics after arterial switch operation: a speckle-tracking echocardiography study. AB - BACKGROUND: The arterial switch operation (ASO) is nowadays the standard procedure for the repair of dextro-transposition of the great arteries (d-TGA). Reduced exercise capacity, coronary artery abnormalities, and reversible myocardial perfusion defects have been demonstrated in patients who have undergone ASO. Despite this, indices of systolic function, assessed by standard echocardiography, are within the normal range. Speckle-tracking echocardiography (STE) can detect early subclinical myocardial abnormalities in several diseases even in the presence of normal left ventricular (LV) ejection fraction. AIM: To assess LV systolic myocardial deformation and torsion in asymptomatic ASO patients with normal LV ejection fraction (>=55%) by using STE. METHODS: We studied 62 asymptomatic patients (26 women) who have undergone single-stage ASO for simple d-TGA, aged 8.5 +/- 5.7 years, with a normal LV ejection fraction (>=55%); 31 age and sex comparable controls (14 women), aged 7.9 +/- 4.9 years. RESULTS: In patients who have undergone ASO, global LV longitudinal strain was significantly lower than that in controls (-19.2 +/- 2.9% vs. -22.7 +/- 2.4%, respectively, P < 0.0001). Longitudinal deformation was significantly impaired in the anterior and both anterior and posterior septal walls. In patients who have undergone ASO global circumferential strain and LV torsion were similar to controls. At multivariate analysis global LV longitudinal strain was significantly correlated only with age at surgery (P = 0.005). CONCLUSION: We demonstrated a significant reduction in longitudinal myocardial deformation correlated with the age at surgical repair, despite a normal LV ejection fraction, in the largest series of asymptomatic ASO patients by using STE. Our findings suggest early (<=7 days) operation on d-TGA patients and continued monitoring of ventricular function by STE. PMID- 26825331 TI - Acidemia in severe acute cardiogenic pulmonary edema treated with noninvasive pressure support ventilation: how severe is the acidosis? PMID- 26825332 TI - Increased extracellular volume fraction in heart failure: does it indicate worse outcomes independently of medical therapy? PMID- 26825333 TI - Increased extracellular volume fraction in nonischaemic dilated cardiomyopathy predicts worse outcomes independently of medical therapy. PMID- 26825334 TI - Exclusive breast feeding is the strongest predictor of infant survival in Northwest Ethiopia: a longitudinal study. AB - Despite the overall national success in reducing infant mortality rate in Ethiopia, infant mortality rate is still high in northwest Amhara region. This study is conducted in one of the high mortality areas with the aim of identifying risk factors that are associated with infant mortality in Northwest Amhara Region, Ethiopia. A prospective open cohort study involving 1752 infants (1472.4518 person years of follow-up) was undertaken from November 2009 to August 2011. Kaplan-Meier Survival analysis was used to estimate infant mortality rate. Risk factors associated with infant mortality were assessed using multivariate Poisson regression. The overall infant mortality rate was 88 per 1000 person years (95% CI: 74.3, 104.9). After controlling other important predictors in multivariate Poisson regression, infants not exclusively breastfed [IRR = 7.86, 95% CI: (5.11, 12.10), )], breast milk initiated after 24 hours of birth [IRR = 4.84,95% CI: (2.94,7.99)], mothers not washing hands with soap after visiting toilet and before feeding child [IRR = 4.61, 95% CI: (2.24, 9.48)], being rural residents [IRR = 2.33, 95% CI: (1.12, 4.88)], infants born within 24 months for the previous birth [IRR = 2.79, 95%CI: (1.88, 4.15)], have increased the risk of infant mortality. In conclusion, exclusive breast feeding is the strongest predictor of infant survival in this predominantly rural setting where hygienic standards are poor. Supporting mothers to exclusively breast feeding which is cost effective, safe and feasible strategy, can help reduce infant mortality in the study setting. PMID- 26825335 TI - Predicting mortality in acutely hospitalized older patients: a retrospective cohort study. AB - Acutely hospitalized older patients have an increased risk of mortality, but at the moment of presentation this risk is difficult to assess. Early identification of patients at high risk might increase the awareness of the physician, and enable tailored decision-making. Existing screening instruments mainly use either geriatric factors or severity of disease for prognostication. Predictive performance of these instruments is moderate, which hampers successive interventions. We conducted a retrospective cohort study among all patients aged 70 years and over who were acutely hospitalized in the Acute Medical Unit of the Leiden University Medical Center, the Netherlands in 2012. We developed a prediction model for 90-day mortality that combines vital signs and laboratory test results reflecting severity of disease with geriatric factors, represented by comorbidities and number of medications. Among 517 patients, 94 patients (18.2 %) died within 90 days after admission. Six predictors of mortality were included in a model for mortality: oxygen saturation, Charlson comorbidity index, thrombocytes, urea, C-reactive protein and non-fasting glucose. The prediction model performs satisfactorily with an 0.738 (0.667-0.798). Using this model, 53 % of the patients in the highest risk decile (N = 51) were deceased within 90 days. In conclusion, we are able to predict 90-day mortality in acutely hospitalized older patients using a model with directly available clinical data describing disease severity and geriatric factors. After further validation, such a model might be used in clinical decision making in older patients. PMID- 26825336 TI - Association of ADHD and Celiac Disease: What Is the Evidence? A Systematic Review of the Literature. AB - OBJECTIVE: This article tries to answer the question whether or not there is evidence for a relationship between celiac disease (CD) and ADHD. A review of the current literature on this topic is provided. METHOD: PUBMED/MEDLINE, Web of Science, and Google scholar were searched to include all published trials on ADHD and CD (no date limitation, both noncontrolled and controlled trials). In addition, the reference list of included studies was screened to find other relevant articles. RESULTS: Eight studies report a possible association between CD and ADHD; however, the results are inconsistent. Only three out of eight studies report a positive correlation between ADHD and CD. CONCLUSION: Up till now, there is no conclusive evidence for a relationship between ADHD and CD. Therefore, it is not advised to perform routine screening of CD when assessing ADHD (and vice versa) or to implement gluten-free diet as a standard treatment in ADHD. PMID- 26825338 TI - Analgesic and CNS Depressant Activities of Sea Anemone Heteractis aurora Nematocyst Toxin. AB - Marine organisms are the excellent sources for biologically active compounds. Cnidarian venoms are potentially valuable materials used for biomedical research and drug development. The present work was carried out to analyse haemolytic, analgesic and CNS depressant activity of sea anemone Heteractis aurora. In haemolytic assay, among the five different RBC blood cells, the chicken blood exhibited maximum hemolytic activity of 64 Hemolytic Unit (HU). The maximum Analgesic Ratio (AR) of 5 recorded at 15 and 30 min interval and minimum was recorded after 45, 60 and 120 min time intervals. In jumping response activity, the maximum of 5 AR recorded at 15, 30 & 45 min and minimum was recorded at 90 & 120 min time intervals. The maximum decrease of depressant activity of 45.07% was determined in CNS depressant activity. Anti-inflammatory activity showed significant inhibition by crude extract of Heteractis aurora. PMID- 26825339 TI - Corticosteroid-Induced MKP-1 Represses Pro-Inflammatory Cytokine Secretion by Enhancing Activity of Tristetraprolin (TTP) in ASM Cells. AB - Exaggerated cytokine secretion drives pathogenesis of a number of chronic inflammatory diseases, including asthma. Anti-inflammatory pharmacotherapies, including corticosteroids, are front-line therapies and although they have proven clinical utility, the molecular mechanisms responsible for their actions are not fully understood. The corticosteroid-inducible gene, mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1, DUSP1) has emerged as a key molecule responsible for the repressive effects of steroids. MKP-1 is known to deactivate p38 MAPK phosphorylation and can control the expression and activity of the mRNA destabilizing protein-tristetraprolin (TTP). But whether corticosteroid-induced MKP-1 acts via p38 MAPK-mediated modulation of TTP function in a pivotal airway cell type, airway smooth muscle (ASM), was unknown. While pretreatment of ASM cells with the corticosteroid dexamethasone (preventative protocol) is known to reduce ASM synthetic function in vitro, the impact of adding dexamethasone after stimulation (therapeutic protocol) had not been explored. Whether dexamethasone modulates TTP in a p38 MAPK-dependent manner in this cell type was also unknown. We address this herein and utilize an in vitro model of asthmatic inflammation where ASM cells were stimulated with the pro-asthmatic cytokine tumor necrosis factor (TNF) and the impact of adding dexamethasone 1 h after stimulation assessed. IL-6 mRNA expression and protein secretion was significantly repressed by dexamethasone acting in a temporally distinct manner to increase MKP-1, deactivate p38 MAPK, and modulate TTP phosphorylation status. In this way, dexamethasone-induced MKP-1 acts via p38 MAPK to switch on the mRNA destabilizing function of TTP to repress pro-inflammatory cytokine secretion from ASM cells. J. Cell. Physiol. 231: 2153-2158, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26825340 TI - Development and optimization of SPE-HPLC-UV/ELSD for simultaneous determination of nine bioactive components in Shenqi Fuzheng Injection based on Quality by Design principles. AB - A method combining solid phase extraction, high performance liquid chromatography, and ultraviolet/evaporative light scattering detection (SPE-HPLC UV/ELSD) was developed according to Quality by Design (QbD) principles and used to assay nine bioactive compounds within a botanical drug, Shenqi Fuzheng Injection. Risk assessment and a Plackett-Burman design were utilized to evaluate the impact of 11 factors on the resolutions and signal-to-noise of chromatographic peaks. Multiple regression and Pareto ranking analysis indicated that the sorbent mass, sample volume, flow rate, column temperature, evaporator temperature, and gas flow rate were statistically significant (p < 0.05) in this procedure. Furthermore, a Box-Behnken design combined with response surface analysis was employed to study the relationships between the quality of SPE-HPLC UV/ELSD analysis and four significant factors, i.e., flow rate, column temperature, evaporator temperature, and gas flow rate. An analytical design space of SPE-HPLC-UV/ELSD was then constructed by calculated Monte Carlo probability. In the presented approach, the operating parameters of sample preparation, chromatographic separation, and compound detection were investigated simultaneously. Eight terms of method validation, i.e., system-suitability tests, method robustness/ruggedness, sensitivity, precision, repeatability, linearity, accuracy, and stability, were accomplished at a selected working point. These results revealed that the QbD principles were suitable in the development of analytical procedures for samples in complex matrices. Meanwhile, the analytical quality and method robustness were validated by the analytical design space. The presented strategy provides a tutorial on the development of a robust QbD compliant quantitative method for samples in complex matrices. PMID- 26825337 TI - Thymic stromal cell subsets for T cell development. AB - The thymus provides a specialized microenvironment in which a variety of stromal cells of both hematopoietic and non-hematopoietic origin regulate development and repertoire selection of T cells. Recent studies have been unraveling the inter- and intracellular signals and transcriptional networks for spatiotemporal regulation of development of thymic stromal cells, mainly thymic epithelial cells (TECs), and the molecular mechanisms of how different TEC subsets control T cell development and selection. TECs are classified into two functionally different subsets: cortical TECs (cTECs) and medullary TECs (mTECs). cTECs induce positive selection of diverse and functionally distinct T cells by virtue of unique antigen-processing systems, while mTECs are essential for establishing T cell tolerance via ectopic expression of peripheral tissue-restricted antigens and cooperation with dendritic cells. In addition to reviewing the role of the thymic stroma in conventional T cell development, we will discuss recently discovered novel functions of TECs in the development of unconventional T cells, such as natural killer T cells and gammadeltaT cells. PMID- 26825341 TI - Preparation and characterization of micro-cell membrane chromatographic column with silica-based porous layer open tubular capillary as cellular membrane carrier. AB - Cell membrane chromatography (CMC) is a powerful tool to study membrane protein interactions and to screen active compounds extracted from natural products. Unfortunately, a large amount of cells are typically required for column preparation in order to carry out analyses in an efficient manner. Micro-CMC (mCMC) has recently been developed by using a silica capillary as a membrane carrier. However, a reduced retention of analytes is generally associated with mCMC mostly due to a low ligand (cellular membrane) capacity. To solve this common problem, in this work a silica-based porous layer open tubular (PLOT) capillary was fabricated and, to the best of our knowledge, for the first time applied to mCMC. The mCMC column was prepared by physical adsorption of rabbit red blood cell (rRBC) membranes onto the inner surface of the PLOT capillary. The effects of the PLOT capillaries fabricated by different feed compositions, on the immobilization amount of cellular membranes (represented by the fluorescence intensity of the capillary immobilized with fluorescein isothiocyanate isomer labeled cellular membranes) and on the dynamic binding capacity (DBC) of verapamil (VP, a widely used calcium antagonist which specific interacts with L type calcium channel proteins located on cellular membrane of rRBC) have been systematically investigated. The fluorescence intensity of the mCMC column when combined with the PLOT capillary was found to be more than five times higher than the intensity using a bare capillary. This intriguing result indicates that the PLOT capillary exhibits a higher cellular membrane capacity. The DBC of VP in the PLOT column was found to be more than nine times higher than that in the bare capillary. An rRBC/CMC column was also prepared for comparative studies. As a result, mCMC provides similar chromatographic retention factors and stability with common CMC; however, the cellular membrane consumption for mCMC was found to be more than 460 times lower than that for CMC. Graphical Abstract Comparision of mCMC chromatograms and SEM images between bare capillary and PLOT capillary. PMID- 26825342 TI - Printing metal-spiked inks for LA-ICP-MS bioimaging internal standardization: comparison of the different nephrotoxic behavior of cisplatin, carboplatin, and oxaliplatin. AB - The study of the distribution of the cytostatic drugs cisplatin, carboplatin, and oxaliplatin along the kidney may help to understand their different nephrotoxic behavior. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) allows the acquisition of trace element images in biological tissues. However, results obtained are affected by several variations concerning the sample matrix and instrumental drifts. In this work, an internal standardization method based on printing an Ir-spiked ink onto the surface of the sample has been developed to evaluate the different distributions and accumulation levels of the aforementioned drugs along the kidney of a rat model. A conventional ink-jet printer was used to print fresh sagittal kidney tissue slices of 4 MUm. A reproducible and homogenous deposition of the ink along the tissue was observed. The ink was partially absorbed on top of the tissue. Thus, this approach provides a pseudo-internal standardization, due to the fact that the ablation sample and internal standard take place subsequently and not simultaneously. A satisfactory normalization of LA-ICP-MS bioimages and therefore a reliable comparison of the kidney treated with different Pt-based drugs were achieved even for tissues analyzed on different days. Due to the complete ablation of the sample, the transport of the ablated internal standard and tissue to the inductively coupled plasma-mass spectrometry (ICP-MS) is practically taking place at the same time. Pt accumulation in the kidney was observed in accordance to the dosages administered for each drug. Although the accumulation rate of cisplatin and oxaliplatin is high in both cases, their Pt distributions differ. The strong nephrotoxicity observed for cisplatin and the absence of such side effect in the case of oxaliplatin could explain these distribution differences. The homogeneous distribution of oxaliplatin in the cortical and medullar areas could be related with its higher affinity for cellular transporters such as MATE2-k. PMID- 26825343 TI - Rapid detection and quantification of tumor marker carbohydrate antigen 72-4 (CA72-4) using a superparamagnetic immunochromatographic strip. AB - Rapid and quantitative detection of biomarkers with high sensitivity and specificity has become a common practice in the clinical diagnosis and treatment of cancer. Herein, a quantitative lateral flow immunoassay (LFIA) based on superparamagnetic nanoparticles (SPMNPs) was developed for detection of carbohydrate antigen 72-4 (CA72-4) in human serum. This direct and rapid method did not involve any sample preparation and was accomplished using a test strip in which a sandwich reaction was performed. Probes on the conjugate pad were prepared by coupling monoclonal antibody CC49 specific to CA72-4 onto SPMNPs. Coupled monoclonal antibody B72.3 and goat anti-mouse IgG were loaded onto a nitrocellulose (NC) membrane, serving as the test and control lines, respectively. Initially, results were evaluated by macroscopic observation. Afterwards, the magnetic signal strength of the reaction area was quantified using a magnetic assay reader (MAR). Several parameters that may influence the detection sensitivity were studied and optimized. Under optimal conditions, the proposed method was capable of detecting as low as 0.38 IU/mL of CA72-4 in 20 min and had a wide detection linearity range (0-100 IU/mL). We evaluated 100 clinical samples (70 positive and 30 negative) to assess the validity of these test strips, which exhibited high sensitivity (99%) and specificity (97%). The results indicated a high rate of accuracy (98.4-102%) and a low relative standard deviation according to the average recovery test. In conclusion, the test strips based on SPMNP probes are a rapid, sensitive, and quantitative method for the detection of CA72-4 and possess great potential in point-of-care testing (POCT). PMID- 26825344 TI - Gas chromatography-mass spectrometry and Raman imaging measurement of squalene content and distribution in human hair. AB - A sensitive and specific gas chromatography-mass spectrometry (GC-MS) method was developed and validated for the measurement of the squalene content from root to tip, in both Chinese black virgin and bleached hair. Deuterated squalene was used as the internal standard. For quantification, selective ion monitoring (SIM) at m/z 410.0 and 347.0 were monitored for squalene and deuterated squalene, respectively. Different methods for the extraction of squalene from ex vivo human hair were compared including organic solvent extraction and acid/alkali hydrolysis. The best extraction efficiency was obtained by using a mixed solvent consisting of chloroform:methanol = 2:1 (v:v). The linear range of squalene ran from 1.0 to 50.0 MUg mL(-1). The limit of detection (LOD) was 0.10 MUg mL(-1) (corresponding to 0.005 mg g(-1) in human hair), which enabled quantification of squalene in human hair at very low level. The recovery of squalene was 96.4 +/- 1.46% (n = 3). Using the above-mentioned mixed solvent extraction, squalene content in human hair was successfully quantified from root to tip. Meanwhile, a Raman imaging method was developed to visualize the squalene distribution in Chinese white virgin hair from cuticle to medulla. PMID- 26825346 TI - Elevated plasma levels of glutamate in children with autism spectrum disorders. AB - Excitatory neurotransmitter signaling through glutamate receptors modulates cognitive functions such as memory and learning, which are usually impaired in autism spectrum disorders (ASD). The aim of this study was to assess the clinical significance of plasma glutamate levels in ASD. Fifty-one children diagnosed with ASD, 51 typically developing children, and 51 children with intellectual disability matched for sex and age were assessed for plasma glutamate at admission. Plasma levels of glutamate were measured by liquid chromatography tandem mass spectrometry and the severity of ASD was evaluated using the Childhood Autism Rating Scale Score. We found that the mean plasma glutamate levels were significantly (P<0.0001) higher in children with ASD compared with healthy controls and intellectual disability controls [36.1 (SD: 8.3) vs. 23.4 (4.2) vs. 24.7 (4.6) uM; P<0.001, respectively]. Levels of glutamate increased with increasing severity of ASD as defined by the Childhood Autism Rating Scale score. Receiver operating characteristics to diagnose ASD showed areas under the curve of glutamate of 0.92 [95% confidence interval (CI), 0.87-0.96], which was superior to high-sensitivity C-reactive protein [0.64 (95% CI, 0.55-0.75), P<0.001] and homocysteine (area under the curve, 0.72; 95% CI, 0.64-0.81; P<0.000). In multivariate logistic regression analysis, glutamate was an independent diagnosis indicator of ASD with an adjusted odds ratio of 1.362 (95% CI, 1.164-1.512; P<0.0001). The present study shows that autistic children had higher plasma levels of glutamate and elevated plasma glutamate levels may play an important role in the pathogenesis of autism. Further larger studies are required to support our findings. PMID- 26825347 TI - Altered resting-state ascending/descending pathways associated with the posterior thalamus in migraine without aura. AB - This study aimed to investigate the dysfunctional ascending/descending pain pathways at the thalamic level in patients with migraine without aura (MWoA) using the effective connectivity analysis of the resting-state functional MRI. Twenty MWoA and 25 matched healthy controls participated in the resting-state functional MRI scans. The directional interactions between the posterior thalamus (PTH) and other brain regions were investigated using the Granger causality analysis and choosing bilateral PTH as two individual seeds. Pearson's correlation analysis was carried out between the abnormal effective connectivity and the headache duration and pain intensity of MWoA. Compared with healthy controls, MWoA showed decreased inflows to the bilateral PTH from the ventromedial prefrontal cortex and the left precuneus/posterior cingulate cortex, decreased outflow from the left PTH to the ipsilateral dorsomedial prefrontal cortex, and increased inflow to the right PTH from the ipsilateral dorsolateral prefrontal cortex. In addition, the abnormal inflows to the right PTH from the ventromedial prefrontal cortex and the right dorsolateral prefrontal cortex correlated positively with the headache duration and pain intensity, respectively. The abnormal ascending/descending pain pathways between the thalamus and these cortical regions indicate a disrupted pain modulation in affective and sensory domains, which suggests a disequilibrium of pain inhibition and facilitation in MWoA. These findings may help to shed light on the pathophysiologic mechanisms of migraine. PMID- 26825348 TI - Dynamic modulation of rTMS on functional connectivity and functional network connectivity to children with cerebral palsy: a case report. AB - Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive treatment tool for the recovery of cerebral palsy (CP). This report describes the modulation effect of rTMS to functional connectivity, functional network connectivity, motor, and cognitive ability following treatment in a child with mild ataxia CP. After receiving 8 months of 0.5 Hz rTMS treatment over the right dorsolateral prefrontal cortex, the child showed a gradual improvement in motor and cognitive-related functional connectivity and functional network connectivity following treatment as well as improved motor, cognitive functions. These pilot results provide the first evidence of the efficiency of 0.5 Hz of rTMS on a child with CP. Further large sample studies are needed to verify and expand the present findings. PMID- 26825349 TI - Recurrent Stroke with Rapid Development of Intracranial Stenoses in Polycythemia Vera. AB - Polycythemia vera (PV) is a blood disorder in which the first expression may be an ischemic stroke. Stroke mechanism in PV is usually attributed to a hypercoagulability state and blood stasis. We report a case of a patient with PV presenting with recurrent ischemic stroke associated with the development of large intracranial stenosis in a period of 1 month. Stenosis was associated with microembolic signals detected by transcranial Doppler. One year later and after hematocrit control, stenosis persisted but microembolic signals disappeared. We discuss similar reports in the literature and the possible pathophysiological mechanism of large-vessel damage in these patients. PMID- 26825351 TI - International Telestroke: The First Five Cases. AB - Telestroke services can improve access to stroke thrombolysis. To address challenges of night time coverage we explored the feasibility of an international telestroke service between Scotland and New Zealand taking advantage of international time zone differences. After addressing medico-legal, governance, and technical issues we tested this international service model and here we present the first 5 cases. Based on our initial experience this new model of care appears feasible and has the potential to improve patient care through reduced doctor fatigue and improved access to expert care in regions where stroke specialist input is limited. PMID- 26825350 TI - Parathyroid Hormone and Subclinical Cerebrovascular Disease: The Atherosclerosis Risk in Communities Brain Magnetic Resonance Imaging Study. AB - BACKGROUND: Elevated parathyroid hormone (PTH) levels have been associated with cardiovascular disease risk factors and events. We hypothesized that elevated PTH levels would also be associated with subclinical cerebrovascular disease. We examined the relationship between elevated PTH level and white matter hyperintensities (WMHs) and subclinical infarcts measured on brain magnetic resonance imaging (MRI). METHODS: PTH was measured at baseline (1993-1994) among participants free of prior clinical stroke who underwent a brain MRI at baseline (n = 1703) and a second brain MRI 10 years later (n = 948). PTH levels of 65 pg/mL or higher were considered elevated (n = 204). Participants who did not return for a follow-up MRI had, at baseline, higher PTH and a greater prevalence of cardiovascular risk factors (P < .05 for all); therefore, multiple imputation was used. The cross-sectional and prospective associations of PTH levels with WMH and MRI-defined infarcts (and their progression) were investigated using multivariable regression models. RESULTS: At baseline, the participants had a mean age of 62 years and were 60% female and 49% black. Cross-sectionally, after adjusting for demographic and lifestyle factors, elevated PTH level was associated with higher WMH score (beta = .19, 95% confidence interval [CI] .04 .35) and increased odds of prevalent infarcts (odds ratio 1.56, 95% CI 1.02 2.36). Results were attenuated after adjustment for potential mediators of this association (i.e., hypertension). No prospective associations were found between PTH and incident infarcts or change in estimated WMH volume, although estimates were imprecise. CONCLUSIONS: Although associated cross-sectionally, we did not confirm any association between elevated PTH level and progression of cerebrovascular changes on brain MRIs obtained 10 years apart. The relationship of PTH with subclinical brain disease warrants further study. PMID- 26825352 TI - Acute Ischemic Stroke with Very Early Clinical Improvement: A National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Trials Exploratory Analysis. AB - BACKGROUND: A high proportion of patients excluded from recombinant tissue plasminogen activator (rt-PA) treatment because of rapid improvement occurring before treatment decision had incomplete recovery. The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trials dataset allows for systematic analyses of very early postrandomization improvement (VEPRIM) in stroke severity as a National Institutes of Health Stroke Scale (NIHSS) score was available for all subjects enrolled in the study at baseline (NIHSSB) and at 2 hours after randomization (NIHSS2H). We explored various definitions of VEPRIM to characterize predictive values for clinical outcomes. METHODS: Post hoc analyses of the NINDS rt-PA Stroke Trials were conducted. VEPRIM was defined as the difference between the NIHSSB and the NIHSS2H scores using 3 approaches: raw, percent, and normalized change. We assessed the association between VEPRIM and 3 month favorable outcome (mRS score of 0-1), symptomatic intracerebral hemorrhage (sICH), and death. RESULTS: In the 624 subjects, every VEPRIM definition was independently associated with an increased probability of favorable outcome: for each unit of change within the VEPRIM definitions, there were 2%-24% (all P < .05) relative increased probability of favorable outcome, 2%-15% (all P < .05) decreased likelihood of death, and 2%-13% (all P < .05) decreased likelihood of sICH. Adjusting for NIHSSB and prestroke mRS scores, there was a significant rt PA treatment effect for improvement seen for all 3 VEPRIM definitions. CONCLUSIONS: VEPRIM predicted favorable outcomes independent of definition and treatment arm. Patients with VEPRIM by any definition, while doing better than patients without VEPRIM, also derived increased clinical benefit when treated with rt-PA compared to placebo. Even with VEPRIM, a substantial percentage of patients had unfavorable outcomes. PMID- 26825353 TI - Featured Article: Inhibition of diabetic cataract by glucose tolerance factor extracted from yeast. AB - Diabetes leads to many complications; among them is the development of cataract. Hyperglycemia brings to increased polyol concentration in the lens, to glycation of lens proteins, and to elevated level of ROS (Reactive Oxygen Species) causing oxidative stress. The glucose tolerance factor (GTF) was found by several groups to decrease hyperglycemia and oxidative stress both in diabetic animals and humans. The aim of our study was to explore the damages induced by high glucose to the eye lens and to assess the protective effects of GTF both in vivo and in vitro The in vivo study included control healthy rats, streptozotocin (STZ) diabetic untreated rats, and STZ diabetic rats orally treated with 15 doses of GTF. The diabetic untreated rats developed cataracts, whereas the development of cataract was totally or partially prevented in GTF treated animals. In vitro studies were done on bovine lenses incubated for 14 days. Half of the lenses were incubated in normal glucose conditions, and half in high glucose conditions (450 mg%). To one group of the normal or high glucose condition GTF was added. The optical quality of all the lenses was measured daily by an automated scanning laser system. The control lenses, whether with or without GTF addition, did not show any reduction in their quality. High glucose conditions induced optical damage to the lenses. Addition of GTF to high glucose conditions prevented this damage. High glucose conditions affected the activity of aldose reductase and sodium potassium ATPase in lens epithelial cell. Addition of GTF decreased the destructive changes induced by high glucose conditions. The amount of soluble cortical lens proteins was decreased and structural changes were detected in lenses incubated in high glucose medium. These changes could be prevented when GTF was added to high glucose medium. Our findings demonstrate the anticataractogenic potential of GTF. PMID- 26825354 TI - Ethanol extract of Zhongtian hawthorn lowers serum cholesterol in mice by inhibiting transcription of 3-hydroxy-3-methylglutaryl-CoA reductase via nuclear factor-kappa B signal pathway. AB - Hawthorn is a berry-like fruit from the species of Crataegus. In China, it has another more famous name, Shan-Zha, which has been used to improve digestion as a traditional Chinese medicine or food for thousands of years. Moreover, during the last decades, hawthorn has received more attention because of its potential to treat cardiovascular diseases. However, currently, only fruits of C. pinnatifida and C. pinnatifida var. major are included as Shan-Zha in the Chinese Pharmacopoeia. In this study, our results showed that the ethanol extract of Zhongtian hawthorn, a novel grafted cultivar of C. cuneata (wild Shan-Zha), could markedly reduce body weight and levels of serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, and liver cholesterol of hyperlipidemia mice. It could suppress the stimulation effect of high-fat diet on the transcription of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and p65, and counteract the downregulation of CYP7A1 and LDLR. In addition, the results of luciferase reporter assay and Western blot showed that the transcriptional activity of HMGCR promoter was inhibited by Zhongtian hawthorn ethanol extract in a dose-dependent manner, while overexpression of p65 could reverse this transcriptional repression effect. These results suggested that Zhongtian hawthorn could provide health benefits by counteracting the high-fat diet-induced hypercholesteolemic and hyperlipidemic effects in vivo, and the mechanism underlying this event was mainly dependent on the suppressive effect of Zhongtian hawthorn ethanol extract on the transcription of HMGCR via nuclear factor-kappa B (NF-kappaB) signal pathway. Therefore, this novel cultivar of hawthorn cultivar which has much bigger fruits, early bearing, high yield, cold resistance, and drought resistance, might be considered as a good alternative to Shan-Zha and has great value in the food and medicine industry. In addition, to our best knowledge, this is also the first report that the extract of Crataegus could suppress the transcription of HMGCR via NF-kappaB signal pathway. PMID- 26825355 TI - A Patient With Atypical Multiple Sulfatase Deficiency. AB - BACKGROUND: Multiple sulfatase deficiency is an autosomal recessive lysosomal storage disorder characterized by the absence of several sulfatases and resulting from mutations in the gene encoding the human C (alpha)-formylglycine-generating enzyme. There have been a variety of biochemical and clinical presentations reported in this disorder. PATIENT DESCRIPTION: We present a 4-year-old girl with clinical findings of microcephaly, spondylolisthesis and neurological regression without ichthyosis, coarse facies, and organomegaly. RESULTS: The child's magnetic resonance imaging demonstrated confluent white matter abnormalities involving the periventricular and deep cerebral white matter with the U-fibers relatively spared. Biochemical testing showing low arylsulfatase A levels were initially thought to be consistent with a diagnosis of metachromatic leukodystrophy. The diagnosis of multiple sulfatase deficiency was pursued when genetic testing for metachromatic leukodystrophy was negative. CONCLUSION: This child illustrates the clinical heterogeneity of multiple sulfatase deficiency and that this disorder can occur without the classic clinical features. PMID- 26825356 TI - Risk factors for obstetric anal sphincter injury: To prolong or to vacuum? AB - INTRODUCTION: An awareness of risk factors for obstetric anal sphincter injuries (OASIS) is essential in order to reduce the occurrence of the primary event. These risk factors are demographic, obstetric and intrapartum related. We aimed to identify the risk factors for OASIS and to examine how modifiable risk factors may be used in order to reduce the incidence of OASIS. METHODS: A retrospective, matched case-control study was conducted in the delivery ward of a single university teaching hospital in Israel, using data from January 2004 to July 2012. All singleton vaginal deliveries at term with OASIS were included. The controls included women matched at a ratio of 1:2 based on gestational age and deliveries that occurred immediately before and after the delivery of the women in the study group. RESULTS: Overall, 113 OASIS were identified. Stepwise conditional logistic regression revealed that the first vaginal birth (OR = 7.6; 95% confidence interval (CI), 3.5-16.3; p < 0.001) particularly after a previous caesarean section (OR = 13.6; 95% CI, 4.7-39.3; p < 0.001) and the length of the second stage (OR 1.5; 95% CI, 1.1-2.1, p = 0.045) were the only risk factors for OASIS. Among 24 primiparous women who already had a prolonged second stage, 15 delivered by vacuum extraction and nine spontaneously; OASIS occurred in eight (53%) and three (33%) women, respectively. Multivariate analysis showed that this difference was not significant (OR = 2.3; 95% CI, 0.4-12.7; p = 0.35). CONCLUSIONS: The first vaginal birth particularly after a caesarean delivery and the length of the second stage increased the risk of OASIS. Vacuum extraction performed to shorten a prolonged second stage is not necessarily protective. PMID- 26825357 TI - Nonalcoholic fatty liver: optimizing pretransplant selection and posttransplant care to maximize survival. AB - PURPOSE OF REVIEW: Nonalcoholic steatohepatitis (NASH) is projected to become the most common indication for liver transplantation in the near future. NASH recipients have concurrent obesity, metabolic, and cardiovascular risks, which directly impact patient selection, posttransplant morbidity and potentially long term outcomes. The purpose of this review is to highlight strategies to optimize pretransplant selection, outcomes, and posttransplant risk modification to optimize patient and graft survival. RECENT FINDINGS: NASH recipients are at risk for pretransplant cardiovascular disease, diabetes mellitus, and related renovascular complications. Stringent selection criteria identify those patients most likely to benefit from liver transplantation without adverse cardiovascular events yet, the incidence of these events remains high in NASH recipients. High BMI imparts postoperative morbidity because of infections, wound complications, and longer lengths of hospital stay. Aggressive management of modifiable risk factors such as obesity, hyperlipidemia, diabetes mellitus, and hypertension is recommended. SUMMARY: Although patient and graft survival in NASH recipients is excellent, long-term reduction in healthcare utilization and outcomes in these patients would benefit from risk factor modification. Periodic reassessment of coronary artery disease and early consideration of bariatric surgery is recommended in this population. PMID- 26825358 TI - Changing prioritization for transplantation: MELD-Na, hepatocellular carcinoma exceptions, and more. AB - PURPOSE OF REVIEW: This article summarizes the landmark events that shaped current deceased donor liver allocation and distribution policy in the USA and to provide an update on recently approved and anticipated policy changes. RECENT FINDINGS: For liver transplant candidates with model for end-stage liver disease more than 11, the 'MELD-Na' equation incorporating serum sodium will be used for allocation starting January 2016. The 'delay and cap' policy for hepatocellular carcinoma delays the start of model for end-stage liver disease exception by 6 months and subsequently grants 28 points, with increases every 3 months thereafter up to a maximum score at 34 points. There is new guidance for exception petitions for neuroendocrine tumors, polycystic liver disease, and primary sclerosing cholangitis. New guidelines for selecting candidates for simultaneous liver-kidney transplant are being developed that may include a 'safety net' for liver-only recipients with posttransplant renal failure. In an effort to provide broader geographic sharing of livers than in the current distribution system, new larger geographic areas are being considered. SUMMARY: Recent policy changes were designed to reduce waitlist mortality, yet inclusion of outcomes measures in allocation and the use of larger geographic distribution units will likely guide future policy changes. PMID- 26825359 TI - Defining the threshold for too sick for transplant. AB - PURPOSE OF REVIEW: The most difficult, and perhaps, most important decision that a clinician makes for a patient on the liver transplant wait-list is when 'not' to proceed with liver transplant. Although an individual may be suitable for transplant surgery at listing, he/she may become too sick while waiting. RECENT FINDINGS: This article reviews four specific conditions that commonly arise on the wait-list that may render a candidate too sick for transplant: advancing age, sarcopenia, acute on chronic liver failure, and nonliver-related medical comorbidities. Each condition, per se, is often not a criterion for delisting; the challenge arises when conditions exist in combination--how does one 'sum' up these conditions to quantify risk? Physical frailty, conceptually, represents the conditions in a candidate that are unlikely to reverse after liver function returns, or will take so long to reverse that the patient will be highly vulnerable to postoperative complications. Pretransplant assessments of physical frailty, which are objective, easily administered, and repeated in the clinical setting, enable us to measure the extent to which these factors, in isolation or combination, will reduce both quantity and quality of life after liver transplant. SUMMARY: In this article, I introduce a framework that incorporates objective pretransplant assessments of physical frailty to facilitate the decision regarding when a patient is too sick for transplant. PMID- 26825361 TI - Associations Among Lactation, Maternal Carbohydrate Metabolism, and Cardiovascular Health: Erratum. PMID- 26825360 TI - Association between intimate partner violence and child morbidity in South Asia. AB - BACKGROUND: This study investigates the association between intimate partner violence (IPV) against women and its impact on child morbidity in the south Asian region. METHODS: The analysis uses logistic regression models with cross sectional nationally representative data from three countries - Bangladesh, India and Nepal. The data have been pooled from 'Demographic and Health Surveys' (DHS) of Bangladesh, Nepal and 'National Family and Health Survey' (NFHS) of India. RESULTS: The study revealed that after controlling for potential confounders, children of mothers experiencing physical violence, sexual violence or both were more likely to have Acute Respiratory Infection (ARI) (OR(adj) 1.57; 95% CI 1.48 1.67), fever (OR(adj) 1.44; 95% CI 1.35-1.54) and diarrhea (OR(adj )1.56; 95% CI 1.44-1.69). CONCLUSIONS: The results highlight that IPV can influence childhood morbidity and support the need to address IPV with a greater focus within current child nutrition and health programs and policies. PMID- 26825365 TI - Pivotal Bioequivalence Study of Clopacin(r), a Generic Formulation of Clopidogrel 75 mg Film-Coated Tablets. AB - INTRODUCTION: Clopacin((r)) (Acino Pharma AG) is a proprietary, besylate salt and lactose-free formulation of the widely-used anti-platelet treatment, clopidogrel. This study aimed to evaluate the bioequivalence of Clopacin((r)) with the originator as reference drug, using a guideline-compliant trial design: open labeled, randomized, single-dose (clopidogrel 75 mg tablet), two-period, crossover trial in 48 healthy male volunteers, with a 7 day wash-out period. METHODS: Plasma samples were collected at intervals and extracted before quantifying clopidogrel concentrations using a fully validated LC-MS/MS method. Bioequivalence of Clopacin((r)) and the reference drug was established by comparison of the primary pharmacokinetic parameters, C max, AUC0-t, and AUC0 infinity. RESULTS: The parameter values were similar for the two products (analysis of variance) and provided Clopacin/reference ratios (least squares means) of >90% and 90% confidence intervals (CIs 84.64-105.50%, 90.43-111.22%, 88.75-110.71%, respectively) that were well within the limits set for defining bioequivalence, according to international guidelines. The respective Clopacin((r)) and reference drug values for mean time to maximal plasma clopidogrel concentration (t max) were 0.83 and 0.91 h, and for terminal elimination half-life were 3.99 and 3.51 h. The intra-subject coefficients of variability for maximal plasma clopidogrel concentration (C max), area under the plasma clopidogrel concentration versus time curve, at 48 h (AUC0-t) and extrapolated to infinity (AUC0-infinity) were 32.2%, 30.2%, and 28.9% (least square means), respectively, and the respective power values were 99.5%, 97.1%, and 95.3%. CONCLUSION: This bioequivalence study provided robust clopidogrel pharmacokinetic data that established the bioequivalence of Clopacin((r)) and the reference originator drug. FUNDING: Acino Pharma AG (formerly Cimex AG). PMID- 26825366 TI - Statewide program to promote institutional delivery in Gujarat, India: who participates and the degree of financial subsidy provided by the Chiranjeevi Yojana program. AB - BACKGROUND: The Chiranjeevi Yojana (CY) is a large public-private partnership program in Gujarat, India, under which the state pays private sector obstetricians to provide childbirth services to poor and tribal women. The CY was initiated statewide in 2007 because of the limited ability of the public health sector to provide emergency obstetric care and high out-of-pocket expenditures in the private sector (where most qualified obstetricians work), creating financial access barriers for poor women. Despite a million beneficiaries, there have been few reports studying CY, particularly the proportion of vulnerable women being covered, the expenditures they incur in connection with childbirth, and the level of subsidy provided to beneficiaries by the program. METHODS: Cross-sectional facility based the survey of participants in three districts of Gujarat in 2012 2013. Women were interviewed to elicit sociodemographic characteristics, out-of pocket expenditures, and CY program details. Descriptive statistics, chi square, and a multivariable logistic regression were performed. RESULTS: Of the 901 women surveyed in 129 facilities, 150 (16 %) were CY beneficiaries; 336 and 415 delivered in government and private facilities, respectively. Only 36 (24 %) of the 150 CY beneficiaries received a completely cashless delivery. Median out-of pocket for vaginal/cesarean delivery among CY beneficiaries was $7/$71. The median degree of subsidy for women in CY who delivered vaginally/cesarean was 85/71 % compared to out-of-pocket expenditure of $44/$208 for vaginal/cesarean delivery paid by non-program beneficiaries in the private health sector. CONCLUSIONS: CY beneficiaries experienced a substantially subsidized childbirth compared to women who delivered in non-accredited private facilities. However, despite the government's efforts at increasing access to delivery services for poor women in the private sector, uptake was low and very few women experienced a cashless delivery. While the long-term focus remains on strengthening the public sector's ability to provide emergency obstetric care, the CY program is a potential means by which the state can ensure its poor mothers have access to necessary care if uptake is increased. PMID- 26825367 TI - Sustained Seizure Control in a Child with Drug Resistant Epilepsy after Subacute Cortical Electrical Stimulation (SCES). PMID- 26825368 TI - Lactate Clearance in Septic Shock Is Not a Surrogate for Improved Microcirculatory Flow. AB - BACKGROUND: Failure to normalize lactate is associated with poor outcomes in septic shock. It has been suggested that persistently elevated lactate may result from regional ischemia due to disturbed and/or heterogenous microcirculatory blood flow. OBJECTIVES: The goal of this study was to determine if lactate clearance (LC) may serve as a surrogate marker for changes in microcirculatory blood flow in patients with septic shock. METHODS: This was a prospective observational study performed within a previously published clinical trial of l carnitine for the treatment of vasopressor-dependent septic shock. Intravital video microscopy was performed at enrollment and 12 hours later, and microcirculatory flow index (MFI) was assessed. Associations between enrollment MFI, lactate, and Sequential Organ Failure Assessment (SOFA) score were determined, in addition to associations between ?MFI, LC, and ?SOFA. A preplanned subgroup analysis of only patients with an elevated initial lactate was performed. RESULTS: We enrolled a total of 31 patients, 23 with survival and sufficient quality videos both at enrollment and at 12 hours. ?MFI, LC, and ?SOFA were 0.1 (interquartile range [IQR] = 0 to 0.3), 18% (IQR = -10% to 46%), and -2 (IQR = -4 to 0). Both ?MFI and LC were associated with ?SOFA (beta = -5.3, p = 0.01; and beta = -3.5, 0.047), but not with each other, even in the subgroup of patients with an initially elevated lactate. CONCLUSIONS: We observed no association between degree of LC and change in microcirculatory blood flow in patients with septic shock. These data suggest against the hypothesis that LC may be used as a surrogate marker of microcirculatory blood flow. PMID- 26825369 TI - Improving Selection Criteria for ALK Inhibitor Therapy in Non-Small Cell Lung Cancer: A Pooled-Data Analysis on Diagnostic Operating Characteristics of Immunohistochemistry. AB - Lung cancer is often diagnosed by molecular markers for prediction and treatment. To date, the golden standard for detection of anaplastic lymphoma kinase (ALK) rearrangements is fluorescence in situ hybridization (FISH). We performed a pooled-data analysis on the diagnostic operating characteristics of immunohistochemistry (IHC) assay on non-small cell lung cancer (NSCLC). We searched Embase, Pubmed, and Springer databases. The results of IHC were evaluated using a modified H-score. We used a 2-level bivariate meta-analysis following a random effect model to summarize sensitivity and specificity and fit hierarchical summary receiver-operating characteristic curves. We also performed sensitivity analysis using different antibodies to investigate potential heterogeneity. Twelve studies consisting of a total of 3754 NSCLC specimens were analyzed. When we defined 1+/2+/3+, 2+/3+, and 3+ as ALK positive, we found the sensitivities to be 99% (95% confidence interval [CI], 97%-100%), 86% (95% CI, 73%-93%), and 56% (95% CI, 36%-74%) and the specificities to be 98% (95% CI, 95% 99%), 99% (95% CI, 99%-100%), and 100% (95% CI, 100%-100%), respectively. We demonstrated that when defining 3+ as positive and 0 as negative the sensitivity was 99% and specificity was 100%. In our sensitivity analysis, we found the sensitivity of D5F3 and 5A4 antibodies to be much higher than that of ALK1. We concluded that IHC scores 0 and 3+ were nearly 100% concordant with FISH-negative and FISH-positive status, respectively. However, IHC scores 1+ and 2+ might require further confirmatory testing by FISH assay. IHC assay using D5F3 and 5A4 antibodies reliably detected NSCLC with ALK rearrangement and may be useful as a screening method to identify these tumors. PMID- 26825370 TI - 3D Xplane Echocardiographic Technique for Validation of Mitral Leaflet Separation to Assess Severity of Mitral Stenosis. AB - BACKGROUND: Determining the severity of mitral stenosis (MS) is important for both prognostic and therapeutic implications. Mitral valve area (MVA) calculation techniques have more limitations. Mitral leaflet separation (MLS) is a precise and operator friendly alternative to planimetry. In contrast to previous researchers, we have used a novel 3D Xplane technique to validate MLS for assessing the severity of MS. 3D Xplane is superior for validation of MLS due to simultaneous real time acquisition of MLS in parasternal long-axis view and corresponding MVA by planimetry in parsternal short-axis view. METHODS: It was a prospective observational single center study. A total of 174 patients with MS were evaluated for MVA estimation by various echocardiographic modalities. Maximum leaflet separation and corresponding planimetered MVA were measured using novel 3D Xplane technique. RESULTS: With 3D Xplane technique, there was strong positive correlation between planimetered MVA and MLS (R = 0.925, P < 0.001), irrespective of coexisting MR (R = 0.886, P < 0.001) or AF (R = 0.912, P < 0.001). Receiver operating characteristic curves of MLS demonstrated AUC for mild and severe MS to be 0.966 and 0.995, respectively. MLS less than 8.62 mm predicted severe MS with 95.5% sensitivity and 94.7% specificity and MLS more than 12.23 mm predicted mild MS with 93.2% sensitivity and 91.4% specificity. CONCLUSION: In our study, a strong correlation between planimetered MVA and MLS was found using 3D Xplane technique. 3D Xplane thus validates and standardizes MLS by excluding errors due to temporal and spatial variations which are important limitations of 2D echocardiography. PMID- 26825371 TI - Serological evidence of tick-borne encephalitis virus infection in moose and deer in Finland: sentinels for virus circulation. AB - BACKGROUND: The incidence of tick-borne encephalitis (TBE) in humans has increased in Finland, and the disease has emerged in new foci. These foci have been investigated to determine the circulating virus subtype, the tick host species and the ecological parameters, but countrywide epidemiological information on the distribution of TBEV has been limited. METHODS: In this study, we screened sera from hunter-harvested wild cervids for the presence of antibodies against tick-borne encephalitis virus (TBEV) with a hemagglutination inhibition test. The positive results were confirmed by a neutralisation assay. RESULTS: Nine (0.74%) of 1213 moose, one (0.74%) of 135 white-tailed deer, and none of the 17 roe deer were found seropositive for TBEV. A close geographical congruence between seropositive cervids and recently reported human TBE cases was observed: nine of the ten seropositive animals were from known endemic areas. CONCLUSIONS: Our results confirm the local circulation of TBEV in several known endemic areas. One seropositive moose had been shot in an area where human TBE cases have not been reported, suggesting a possible new focus. Moose appear to be a useful sentinel animal for the presence of TBEV in the taiga region. PMID- 26825373 TI - Development of complex-shaped liver multicellular spheroids as a human-based model for nanoparticle toxicity assessment in vitro. AB - The emergence of human-based models is incontestably required for the study of complex physiological pathways and validation of reliable in vitro methods as alternative for in vivo studies in experimental animals for toxicity assessment. With this objective, we have developed and tested three dimensional environments for cells using different types of hydrogels including transglutaminase-cross linked gelatin, collagen type I, and growth-factor depleted Matrigel. Cells grown in Matrigel exhibited the greatest cell proliferation and spheroid diameter. Moreover, analysis of urea and albumin biosynthesis revealed that the created system allowed the immortalized liver cell line HepG2 to re-establish normal hepatocyte-like properties which were not observed under the conditions of conventional cell cultures. This study presents a scalable technology for production of complex-shaped liver multicellular spheroids as a system which improves the predictive value of cell-based assays for safety and risk assessment. The time- and dose-dependent toxicity of nanoparticles demonstrates a higher cytotoxic effect when HepG2 cells grown as monolayer than embedded in hydrogels. The experimental setup provided evidence that the cell environment has significant influence on cell sensitivity and that liver spheroid is a useful and novel tool to examine nanoparticle dosing effect even at the level of in vitro studies. Therefore, this system can be applied to a wide variety of potentially hostile compounds in basic screening to provide initial warning of adverse effects and trigger subsequent analysis and remedial actions. PMID- 26825372 TI - DNA damage-inducible transcript 4 (DDIT4) mediates methamphetamine-induced autophagy and apoptosis through mTOR signaling pathway in cardiomyocytes. AB - Methamphetamine (METH) is an amphetamine-like psychostimulant that is commonly abused. Previous studies have shown that METH can induce damages to the nervous system and recent studies suggest that METH can also cause adverse and potentially lethal effects on the cardiovascular system. Recently, we demonstrated that DNA damage-inducible transcript 4 (DDIT4) regulates METH induced neurotoxicity. However, the role of DDIT4 in METH-induced cardiotoxicity remains unknown. We hypothesized that DDIT4 may mediate METH-induced autophagy and apoptosis in cardiomyocytes. To test the hypothesis, we examined DDIT4 protein expression in cardiomyocytes and in heart tissues of rats exposed to METH with Western blotting. We also determined the effects on METH-induced autophagy and apoptosis after silencing DDIT4 expression with synthetic siRNA with or without pretreatment of a mTOR inhibitor rapamycin in cardiomyocytes using Western blot analysis, fluorescence microscopy and TUNEL staining. Our results showed that METH exposure increased DDIT4 expression and decreased phosphorylation of mTOR that was accompanied with increased autophagy and apoptosis both in vitro and in vivo. These effects were normalized after silencing DDIT4. On the other hand, rapamycin promoted METH-induced autophagy and apoptosis in DDIT4 knockdown cardiomyocytes. These results suggest that DDIT4 mediates METH-induced autophagy and apoptosis through mTOR signaling pathway in cardiomyocytes. PMID- 26825374 TI - TRPV currents and their role in the nociception and neuroplasticity. AB - Transient receptor potential channels sensitive to vanilloids (TRPVs) are group of ion channels which are sensitive to various tissue damaging signals and their activation is generally perceived as pain. Therefore, they are generally named as nociceptors. Understanding their activation and function as well as their interaction with intracellular pathways is crucial for the development of pharmacological interference in order to reduce pain perception. The current review summarizes basic facts in regard to TRPV and discusses their relevance in the sensing of (pain-) signals and their intracellular processing, focussing on their modulation of the intracellular calcium ([Ca(2+)]i) signal. Furthermore we discuss the basic mechanisms how the modification of [Ca(2+)]i through TRPV might induce long-term-potentiation (LTP) or long-term- depression (LTD) and from "memories" of pain. Understanding of these mechanisms is needed to localize the best point of interference for pharmacological treatment. Therefore, high attention is given to highlight physiological and pathological processes and their interaction with significant modulators and their roles in neuroplasticity and pain modulation. PMID- 26825375 TI - Is the number of Medicaid providers really that important? PMID- 26825376 TI - Effective Screening for Emotional Distress in Refugees: The Refugee Health Screener. AB - Screening for emotional distress is important, but not widely available. This study assesses the utility of the Refugee Health Screener 15 (RHS-15) in a public health setting. Refugee Health Screener 15 and diagnostic proxy (DP) instruments assessing anxiety, depression, and posttraumatic stress disorder were administered to refugees from 3 countries at their public health examination. Properties of the RHS-15 and its components were evaluated utilizing appropriate methods. Scale Cronbach alpha was 0.95, and a factor analysis identified 1 factor accounting for 66% of scale variance. Refugee Health Screener 15 scores and cases discriminated between refugee groups similar to DPs. Refugee Health Screener 15 case sensitivity and specificity to DPs were acceptable (>=0.87/0.77). A shorter, 13-item component had acceptable metric properties. The RHS-15 appears to be a valid screener for emotional distress of refugees. The 13-item scale may be more efficient and as efficacious for case identification. The critical public health need and recommendations for implementation are discussed. PMID- 26825377 TI - Adult Attention Deficit Hyperactivity Disorder Symptoms, Perceived Stress, and Well-Being: The Role of Early Maladaptive Schemata. AB - Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent chronic neuropsychiatric disorders, severely affecting the emotional well-being of children as well as of adults. It has been suggested that individuals who experience symptoms of ADHD develop maladaptive schemata of failure, impaired self-discipline, social isolation, and shame. These schemata may then contribute to impaired emotional well-being by increasing unhelpful responses to stressful life events. However, to date, no empirical research has tested this theoretical proposition. In a sample of 204 nonclinical adults, we conducted a serial multiple mediator analysis, which supported the proposed model. More severe ADHD symptoms were associated with higher levels of perceived stress both directly and indirectly through stronger maladaptive schemata, which, in turn, were related to lower levels of emotional well-being. Results suggest that identifying and modifying maladaptive schemata may be an important addition to psychotherapy for adult ADHD patients. PMID- 26825378 TI - Assessing the safety of cosmetic chemicals: Consideration of a flux decision tree to predict dermally delivered systemic dose for comparison with oral TTC (Threshold of Toxicological Concern). AB - Threshold of Toxicological Concern (TTC) aids assessment of human health risks from exposure to low levels of chemicals when toxicity data are limited. The objective here was to explore the potential refinement of exposure for applying the oral TTC to chemicals found in cosmetic products, for which there are limited dermal absorption data. A decision tree was constructed to estimate the dermally absorbed amount of chemical, based on typical skin exposure scenarios. Dermal absorption was calculated using an established predictive algorithm to derive the maximum skin flux adjusted to the actual 'dose' applied. The predicted systemic availability (assuming no local metabolism), can then be ranked against the oral TTC for the relevant structural class. The predictive approach has been evaluated by deriving the experimental/prediction ratio for systemic availability for 22 cosmetic chemical exposure scenarios. These emphasise that estimation of skin penetration may be challenging for penetration enhancing formulations, short application times with incomplete rinse-off, or significant metabolism. While there were a few exceptions, the experiment-to-prediction ratios mostly fell within a factor of 10 of the ideal value of 1. It can be concluded therefore, that the approach is fit-for-purpose when used as a screening and prioritisation tool. PMID- 26825379 TI - Aging and computational systems biology. AB - Aging research is undergoing a paradigm shift, which has led to new and innovative methods of exploring this complex phenomenon. The systems biology approach endeavors to understand biological systems in a holistic manner, by taking account of intrinsic interactions, while also attempting to account for the impact of external inputs, such as diet. A key technique employed in systems biology is computational modeling, which involves mathematically describing and simulating the dynamics of biological systems. Although a large number of computational models have been developed in recent years, these models have focused on various discrete components of the aging process, and to date no model has succeeded in completely representing the full scope of aging. Combining existing models or developing new models may help to address this need and in so doing could help achieve an improved understanding of the intrinsic mechanisms which underpin aging. PMID- 26825380 TI - Feasibility of self-administered sleep assessment in older women in the Women's Health Initiative (WHI). AB - PURPOSE: Laboratory-based polysomnography (PSG) is the gold standard assessment of sleep disordered breathing (SDB). In large cohort studies and clinical trials, however, these overnight procedures can be expensive and burdensome to participants, especially older adults. In preparation for a large observational study, we determined the feasibility of self-administering two devices mailed to participants' homes that estimate indices of SDB. METHODS: In two separate studies, older women enrolled in the Women's Health Initiative (WHI) Memory Study extension aged mean (SD) 85.77 (2.98) years who were not using supplemental oxygen and consented to being in the feasibility study completed either an in home, self-administered overnight sleep assessment using a multi-sensor device that measured oximetry, nasal pressure, chest effort, and snoring (ApneaLink(TM)) (N = 58), or a wrist-worn oximeter (NoninWristOx2(TM)) (N = 33). A follow-up questionnaire assessed the devices' acceptability and important sleep-related exposures. RESULTS: Although the multi-sensor device was assessed only in older women with no cognitive impairment, the proportion of completed interpretable sleep studies was low (54 %) and participants reported needing help to administer the device successfully. In contrast, the wrist-worn device was used in women with either no or mild cognitive impairment (MCI), completion rates were higher (100 %), and women reported being able to administer the device independently. CONCLUSIONS: These studies demonstrated that home-based self-administered assessments of SDB are feasible in older adults with and without cognitive impairment using wrist-worn oximetry. These data support the feasibility of using simple oximetry measurements to provide indices of overnight intermittent hypoxemia in large observational studies and clinical trials. PMID- 26825381 TI - Motivation of medical students: selection by motivation or motivation by selection. AB - BACKGROUND: Medical schools try to implement selection procedures that will allow them to select the most motivated students for their programs. Though there is a general feeling that selection stimulates student motivation, conclusive evidence for this is lacking. The current study aims to use the perspective of Self determination Theory (SDT) of motivation as a lens to examine how medical students' motivation differs in relation to different selection procedures. The hypotheses were that 1) selected students report higher strength and autonomous motivation than non-selected students, and 2) recently selected students report higher strength and autonomous motivation than non-selected students and students who were selected longer ago. METHODS: First- (Y1) and fourth-year (Y4) medical students in the six-year regular programme and first-year students in the four year graduate entry programme (GE) completed questionnaires measuring motivation strength and type (autonomous-AM, controlled-CM). Scores were compared between students admitted based on selection, lottery or top pre-university GPA (top GPA) using ANCOVAs. Selected students' answers on open-ended questions were analysed using inductive thematic analysis to identify reasons for changes in motivation. RESULTS: The response rate was 61.4 % (n = 357). Selected students (Y1, Y4 and GE) reported a significantly higher strength of motivation than non-selected students (Y1 and Y4 lottery and top GPA) (p < 0.01). Recently selected students (Y1 and GE) reported significantly higher strength (p < 0.01) and higher AM (p < 0.01) and CM (p < 0.05) than non-selected students (lottery and top GPA) and Y4 students who were selected three years ago. Students described that being selected enhanced their motivation as they felt autonomous, competent and that they belonged to a special group. These reported reasons are in alignment with the basic psychological needs described by Self-Determination Theory as important in enhancing autonomous motivation. CONCLUSIONS: A comprehensive selection procedure, compared to less demanding admission procedures, does not seem to yield a student population which stands out in terms of autonomous motivation. The current findings indicate that selection might temporarily enhance students' motivation. The mechanism through which this occurs seems to be through feelings of autonomy, competence and relatedness inspired by selection. PMID- 26825383 TI - NHS hits target on reducing carbon emissions. PMID- 26825382 TI - Identification and reproducibility of diagnostic DNA markers for tuber starch and yield optimization in a novel association mapping population of potato (Solanum tuberosum L.). AB - KEY MESSAGE: SNPs in candidate genes Pain - 1, InvCD141 (invertases), SSIV (starch synthase), StCDF1 (transcription factor), LapN (leucine aminopeptidase), and cytoplasm type are associated with potato tuber yield, starch content and/or starch yield. Tuber yield (TY), starch content (TSC), and starch yield (TSY) are complex characters of high importance for the potato crop in general and for industrial starch production in particular. DNA markers associated with superior alleles of genes that control the natural variation of TY, TSC, and TSY could increase precision and speed of breeding new cultivars optimized for potato starch production. Diagnostic DNA markers are identified by association mapping in populations of tetraploid potato varieties and advanced breeding clones. A novel association mapping population of 282 genotypes including varieties, breeding clones and Andean landraces was assembled and field evaluated in Northern Spain for TY, TSC, TSY, tuber number (TN) and tuber weight (TW). The landraces had lower mean values of TY, TW, TN, and TSY. The population was genotyped for 183 microsatellite alleles, 221 single nucleotide polymorphisms (SNPs) in fourteen candidate genes and eight known diagnostic markers for TSC and TSY. Association test statistics including kinship and population structure reproduced five known marker-trait associations of candidate genes and discovered new ones, particularly for tuber yield and starch yield. The inclusion of landraces increased the number of detected marker-trait associations. Integration of the present association mapping results with previous QTL linkage mapping studies for TY, TSC, TSY, TW, TN, and tuberization revealed some hot spots of QTL for these traits in the potato genome. The genomic positions of markers linked or associated with QTL for complex tuber traits suggest high multiplicity and genome wide distribution of the underlying genes. PMID- 26825384 TI - Stereoscopic Analysis of Silicone Breast Implant Shells Damaged by Surgical Instruments. PMID- 26825385 TI - Anatomical Considerations to Prevent Facial Nerve Injury: Insights on Frontal Branch and Cervicofacial Trunk Nerve Anatomy in SMAS Face Lifts. PMID- 26825386 TI - Repair of a anastomotic-vaginal fistula with biological mesh (PermacolTM) after surgery for low rectal cancer. PMID- 26825387 TI - Erratum to: Environmental management practices in the Lebanese pharmaceutical industries: implementation strategies and challenges. PMID- 26825388 TI - A Case of Signet Ring Cell Carcinoma of the Gallbladder Which Was Treated by Aggressive Surgery and Intensive Adjuvant Chemotherapy. PMID- 26825390 TI - Unfavourable results from using the transarticular pin technique to stabilise luxated hips in 12 dogs under 8 kg. PMID- 26825389 TI - Mitochondrial permeability transition pore: a promising target for the treatment of Parkinson's disease. AB - Among the neurodegenerative diseases (ND), Parkinson's disease affects 6.3 million people worldwide characterized by the progressive loss of dopaminergic neurons in substantia nigra. The mitochondrial permeability transition pore (mtPTP) is a non-selective voltage-dependent mitochondrial channel whose opening modifies the permeability properties of the mitochondrial inner membrane. It is recognized as a potent pharmacological target for diseases associated with mitochondrial dysfunction and excessive cell death including ND such as Parkinson's disease (PD). Imbalance in Ca2+ concentration, change in mitochondrial membrane potential, overproduction of reactive oxygen species (ROS), or mutation in mitochondrial genome has been implicated in the pathophysiology of the opening of the mtPTP. Different proteins are released by permeability transition including cytochrome c which is responsible for apoptosis. This review aims to discuss the importance of PTP in the pathophysiology of PD and puts together different positive as well as negative aspects of drugs such as pramipexole, ropinirole, minocyclin, rasagilin, and safinamide which act as a blocker or modifier for mtPTP. Some of them may be detrimental in their neuroprotective nature. PMID- 26825391 TI - Recognition of genetic predisposition in pediatric cancer patients: An easy-to use selection tool. AB - Genetic predisposition for childhood cancer is under diagnosed. Identifying these patients may lead to therapy adjustments in case of syndrome-related increased toxicity or resistant disease and syndrome-specific screening programs may lead to early detection of a further independent malignancy. Cancer surveillance might also be warranted for affected relatives and detection of a genetic mutation can allow for reproductive counseling. Here we present an easy-to-use selection tool, based on a systematic review of pediatric cancer predisposing syndromes, to identify patients who may benefit from genetic counseling. The selection tool involves five questions concerning family history, the type of malignancy, multiple primary malignancies, specific features and excessive toxicity, which results in the selection of those patients that may benefit from referral to a clinical geneticist. PMID- 26825393 TI - Eric Davidson's early years in development. PMID- 26825394 TI - My time with Eric Davidson. PMID- 26825392 TI - Eric Davidson: Steps to a gene regulatory network for development. AB - Eric Harris Davidson was a unique and creative intellectual force who grappled with the diversity of developmental processes used by animal embryos and wrestled them into an intelligible set of principles, then spent his life translating these process elements into molecularly definable terms through the architecture of gene regulatory networks. He took speculative risks in his theoretical writing but ran a highly organized, rigorous experimental program that yielded an unprecedentedly full characterization of a developing organism. His writings created logical order and a framework for mechanism from the complex phenomena at the heart of advanced multicellular organism development. This is a reminiscence of intellectual currents in his work as observed by the author through the last 30-35 years of Davidson's life. PMID- 26825395 TI - Eric Davidson, friend, colleague and mentor. PMID- 26825396 TI - Interview with Eric Davidson. PMID- 26825397 TI - Eric Davidson: Master of the universe. PMID- 26825398 TI - Cytosolic ppGpp accumulation induces retarded plant growth and development. AB - In bacteria a second messenger, guanosine 5'-diphosphate 3'-diphosphate (ppGpp), synthesized upon nutrient starvation, controls many gene expressions and enzyme activities, which is necessary for growth under changeable environments. Recent studies have shown that ppGpp synthase and hydrolase are also conserved in eukaryotes, although their functions are not well understood. We recently showed that ppGpp-overaccumulation in Arabidopsis chloroplasts results in robust growth under nutrient-limited conditions, demonstrating that the bacterial-like stringent response at least functions in plastids. To test if ppGpp also functions in the cytosol, we constructed the transgenic Arabidopsis expressing Bacillus subtilis ppGpp synthase gene yjbM. Upon induction of the gene, the mutant synthesizes ~10-20-fold higher levels of ppGpp, and its fresh weight was reduced to ~80% that of the wild type. These results indicate that cytosolic ppGpp negatively regulates plant growth and development. PMID- 26825399 TI - General Ser/Thr Kinases Pharmacophore Approach for Selective Kinase Inhibitors Search as Exemplified by Design of Potent and Selective Aurora A Inhibitors. AB - A general pharmachophore model for various types of Ser/Thr kinases was developed. Search for the molecules fitting to this pharmacophore among ASINEX proprietary library revealed a number of compounds, which were tested and appeared to possess some activity against several Ser/Thr kinases such as Aurora A, Aurora B and Haspin. The possibility of performing the fine-tuning of the general Ser/Thr pharmacophore to desired types of kinase to get active and selective inhibitors was exemplified by Aurora A kinase. As a result, several hits in 3-5 nm range of activity against Aurora A kinase with rather good selectivity and ADME properties were obtained. PMID- 26825400 TI - Case of cutaneous mucinosis with HIV infection. PMID- 26825402 TI - Pay for Performance-Are You Prepared? PMID- 26825403 TI - Effect of Scopolamine Patch Use on Postoperative Voiding Function After Transobturator Slings. AB - OBJECTIVES: The aim of this study was to determine whether the use of a preoperative transdermal scopolamine (TDS) patch for postoperative nausea and vomiting prophylaxis affects the success of a voiding trial after a transobturator tape sling procedure. METHODS: This study is a retrospective cohort study of adult women who underwent a transobturator tape sling procedure without concomitant procedures from February 1, 2009 through August 1, 2010. The exposed group included all eligible women who received a preoperative TDS patch. For each exposed woman, we selected the next 2 consecutive eligible women who did not receive a TDS patch to be included in the unexposed group. The primary outcome was postoperative voiding trial failure. RESULTS: We identified 35 women who met eligibility criteria and used a preoperative TDS patch, and included 70 women who did not use a preoperative TDS. A significantly higher proportion of women in the TDS patch group (54.3%) failed their voiding trial than in the group that did not receive TDS (7.1%, P <= 0.001). A history of an incontinence procedure, older age, and higher body mass index strengthened the association between TDS patch and voiding trial failure. The adjusted model yielded a risk ratio for voiding trial failure of 13.8 (95% confidence interval, 5.2-36.5) for women who received TDS patch compared with those who did not. CONCLUSIONS: The results of this study demonstrate that use of TDS patches for postoperative nausea and vomiting prophylaxis may negatively affect the success of voiding trials after transobturator tape sling procedures. PMID- 26825404 TI - Pelvic Floor Disorders Registry: Study Design and Outcome Measures. AB - Pelvic floor disorders affect up to 24% of adult women in the United States, and many patients with pelvic organ prolapse (POP) choose to undergo surgical repair to improve their quality of life. While a variety of surgical repair approaches and techniques are utilized, including mesh augmentation, there is limited comparative effectiveness and safety outcome data guiding best practice. In conjunction with device manufacturers, federal regulatory organizations, and professional societies, the American Urogynecologic Society developed the Pelvic Floor Disorders Registry (PFDR) designed to improve the quality of POP surgery by facilitating quality improvement and research on POP treatments. The PFDR will serve as a resource for surgeons interested in benchmarking and outcomes data and as a data repository for Food and Drug Administration-mandated POP surgical device studies. Provider-reported clinical data and patient-reported outcomes will be collected prospectively at baseline and for up to 3 years after treatment. All data elements including measures of success, adverse events, and surgeon characteristics were identified and defined within the context of the anticipated multifunctionality of the registry, and with collaboration from multiple stakeholders. The PFDR will provide a platform to collect high-quality, standardized patient-level data from a variety of nonsurgical (pessary) and surgical treatments of POP and other pelvic floor disorders. Data from this registry may be used to evaluate short- and longer-term treatment outcomes, patient-reported outcomes, and complications, as well as to identify factors associated with treatment success and failure with the overall goal of improving the quality of care for women with these conditions. PMID- 26825405 TI - Attitudes Regarding Labial Hypertrophy and Labiaplasty: A Survey of Members of the Society of Gynecologic Surgeons and the North American Society for Pediatric and Adolescent Gynecology. AB - OBJECTIVE: The aim of this study was to describe gynecologists' attitudes toward labial hypertrophy and explore possible differences among providers for pediatric/adolescent patients. METHODS: This was an institutional review board approved, cross-sectional survey of physician attendees at 2 national meetings in 2014: the Society of Gynecologic Surgeons (SGS) and the North American Society for Pediatric and Adolescent Gynecology (NASPAG). The survey was designed to query demographics and impressions regarding labial hypertrophy and labiaplasty. RESULTS: Three hundred sixty-five surveys were completed (response rate, 50%); 268 were analyzed: 55% from SGS and 45% from NASPAG. Most were older than 41 years; 170 (63%) were women, and 93 (35%) were men. More men than women attended SGS (60%); however, women were the majority at NASPAG (94%).Most respondents believed labial hypertrophy to be infrequently reported and "a condition that impacts body image." Common symptoms were "discomfort with exercise" and "dissatisfaction with appearance naked." The majority felt this to impact sexual function "in some cases," citing "self-esteem" and "comfort" most often.Concerning therapies for provided labial hypertrophy, 83% of practitioners provide reassurance, whereas 77% would offer labiaplasty. Expertise with labiaplasty varied; 28% felt "very comfortable," and 11% felt "very uncomfortable."Provider preference for treatment differed based on meeting attendance. After logistic regression controlling for sex and age, attendance at SGS remained associated with offering labiaplasty (P = 0.001; odds ratio, 4.1; 95% confidence interval, 1.8-9.3), whereas NASPAG attendance was associated with providing reassurance (P = 0.008; odds ratio, 0.30; 95% confidence interval, 0.10 0.70). CONCLUSIONS: Although the majority surveyed view labial hypertrophy to be bothersome, gynecologists caring for our youngest patients are more likely to provide reassurance. Consensus guidelines are needed to aid practitioners in appropriate management of labial hypertrophy. PMID- 26825406 TI - The Role of Obesity in Success and Complications in Patients Undergoing Retropubic Tension-Free Vaginal Tape Surgery. AB - OBJECTIVES: The aim of this study was to examine the impact of obesity on the success rate of and complications from retropubic tension-free vaginal tape (TVT) midurethral slings for stress urinary incontinence (SUI). METHODS: A retrospective, cohort study was performed on patients with retropubic TVT surgery between 2008 and 2014. Demographic, outcome, and complication data were obtained from electronic medical records and analyzed using logistic regression, analysis of variance, and multivariate regression analysis. Short-term (1-2 weeks) and long-term (2 months) outcomes were measured. RESULTS: Two hundred twenty-seven patients were included; 100 (44%) were of normal weight, 71 (31%) were overweight, and 56 (24%) were obese. Overall SUI cure rates were high, although the obese group had a lower cure rate. Compared with normal weight, overweight patients had a 2.43 times higher odds (P = 0.14) of short-term complaints of persistent SUI, whereas obese patients had a 3.56 times higher odds (P = 0.03). Similar failure rates were seen at 2 months among the groups. Odds of intraoperative complications did not differ between overweight and normal weight (odds ratio [OR], 0.64; P = 0.319) and obese and normal weight (OR, 0.90; P = 0.83) patients. Postoperative complications did not differ between overweight and normal weight (OR, 0.40; P = 0.27) and obese and normal weight (OR, 1.45; P = 0.54) patients. CONCLUSIONS: Obese women undergoing retropubic TVT surgery had a 3.56 increased odds of short-term complaints of SUI compared with normal weight patients, but 2-month failure rates were similar. Obese and overweight patients were equally likely to have complications from TVT. PMID- 26825407 TI - Thirty Years of Cystocele/Rectocele Repair in the United States. AB - OBJECTIVE: A growing body of evidence suggests an increased role for apical support in the treatment of pelvic organ prolapse regardless of phenotype. The objective of this study was to determine whether changes in cystocele/rectocele diagnosis and surgical management for the last 30 years reflect this changing paradigm. METHODS: Data from the National Hospital Discharge Survey were mined from 1979 to 2009 for diagnosis and procedure codes. Records were categorized according to predefined combinations of diagnosis and procedure codes and weighted according to the National Hospital Discharge Survey data set. Pearson chi test was used to evaluate the changes in population proportions during the study interval. RESULTS: The proportion of isolated cystocele/rectocele diagnoses decreased from 1979 to 2009 (56.5%, n = 88,548, to 34.8%, n = 31,577). The proportion of isolated apical defect diagnoses increased from 1979 to 2009 (38.4%, n = 60,223, to 60.8%, n = 55,153). There was a decrease in the frequency of isolated cystocele/rectocele repair procedures performed from 1979 to 2009 (96.3%, n = 150,980, to 67.7%, n = 61,444), whereas there was an increase in isolated apical defect repair procedures (2.5%, n = 3929, to 22.5%, n = 20,450). The proportion of cystocele/rectocele plus apical defect procedures also increased (1.2%, n = 1879, to 9.7%, n = 8806). Furthermore, 87.0% of all studied diagnostic groups were managed by cystocele/rectocele repair alone. CONCLUSIONS: Surgeons have responded to the increased contribution of apical support defects to cystocele/rectocele by modifying their diagnostic coding practices. Unfortunately, their surgical choices remain largely rooted in an older paradigm. PMID- 26825408 TI - To Pack or Not to Pack? A Randomized Trial of Vaginal Packing After Vaginal Reconstructive Surgery. AB - OBJECTIVE: Placement of vaginal packing after pelvic reconstructive surgery is common; however, little evidence exists to support the practice. Furthermore, patients have reported discomfort from the packs. We describe pain and satisfaction in women treated with and without vaginal packing. METHODS: This institutional review board-approved randomized-controlled trial enrolled patients undergoing vaginal hysterectomy with prolapse repairs. The primary outcome was visual analog scales (VASs) for pain on postoperative day 1. Allocation to "packing" ("P") or "no-packing" ("NP") arms occurred intraoperatively at the end of surgery. Visual analog scales regarding pain and satisfaction were completed early on postoperative day 1 before packing removal. Visual analog scale scores for pain, satisfaction, and bother attributable to packing were recorded before discharge. All packing and perineal pads were weighed to calculate a "postoperative vaginal blood loss." Perioperative data were collected from the hospital record. Our sample size estimation required 74 subjects. RESULTS: Ninety three women were enrolled. After exclusions, 77 were randomized (P, 37; NP, 40). No differences were found in surgical information, hemoglobin levels, or narcotic use between groups. However, "postoperative vaginal blood loss" was greater in packed subjects (P < 0.001). Visual analog scale scores for pain before removal of packing (P, 41.6 vs NP, 46.3; P = 0.43] and before discharge (P, 35.0 vs NP, 40.0; P = 0.43] were not significantly different between treatment arms. Likewise, VAS scores for satisfaction before removal of packing (P, 81.0 vs NP, 90.0; P = 0.08] and before discharge (P, 90.0 vs NP, 90.5; P = 0.60] were not significantly different. Packed patients noted lower nursing verbal pain scores (P = 0.04) and used less ketorolac (P = 0.01). Bother from packing was low overall. CONCLUSIONS: Although there was no difference based on VAS, women receiving vaginal packing had lower nursing documented pain and used less ketorolac than packed women. Vaginal packing may provide benefit and can remain part of the surgical practice. PMID- 26825409 TI - Patient Satisfaction After Sling Revision for Voiding Dysfunction After Sling Placement. AB - OBJECTIVE: The aim of this study was to evaluate patient-reported outcomes after sling release for obstructive voiding after sling operation for female stress urinary incontinence. METHODS: All female patients who had sling release for obstructive voiding at Mayo Clinic in Rochester, Minnesota, from January 1, 2000, through October 31, 2008, were identified and mailed a survey including validated questions for voiding symptoms. A composite outcome for surgical success was chosen in which participants reported global improvement (at least "much better") and complete satisfaction on a 7-point Likert scale. Logistic regression analysis was used to identify clinical and surgical predictors of this outcome. RESULTS: In total, 101 women were identified, of which 98 were alive at the time of mailing, and 55 women (56.1%) responded to the survey. Surgery before sling release was a synthetic midurethal sling in 62 patients and biologic sling in 39 patients. Clinical characteristics among mailing responders and nonresponders were similar aside from time from revision surgery to survey (median, 38.8 vs 54.6 months; P = 0.05). Overall, 23 (41.8%) of the 55 responding patients met the predefined criteria for surgical success. Multivariable analysis identified age younger than 60 years (odds ratio [OR], 4.22; P = 0.02), absence of overactive bladder symptoms before sling release (OR, 3.99; P = 0.04), and type of sling release (sling incision or loosening vs partial or complete excision) (OR, 3.78; P = 0.05) as predictors of success. CONCLUSIONS: Of responders, 23 (41.8%) reported global improvement and satisfaction. Younger age, lack of documented overactive bladder symptoms before sling release, and performing sling release with sling incision or loosening rather than partial or complete excision were associated with better satisfaction and patient-reported improvement. PMID- 26825410 TI - Vaginal Calculus in a Woman With Mixed Urinary Incontinence and Vaginal Mesh Exposure. AB - Vaginal calculi are extremely rare and are most commonly encountered in the setting of an urethrovaginal or vesicovaginal fistula. We present a case of a 72 year-old woman with mixed urinary incontinence and vaginal mesh exposure incidentally found to have a large vaginal calculus. We removed the calculus surgically and analyzed the components. Results demonstrated the presence of ammonium-magnesium phosphate hexahydrate and carbonate apatite. PMID- 26825411 TI - Pharmacological Agents to Decrease New Episodes of Recurrent Lower Urinary Tract Infections in Postmenopausal Women. A Systematic Review. AB - OBJECTIVES: The purpose of this systematic review was to evaluate and summarize pharmacological interventions evaluated in randomized clinical trials designed to prevent recurrent episodes of urinary tract infections (UTIs) in postmenopausal women. METHODS: Excerpta Medica dataBASE, Pubmed, Medline, and Cochrane Library were accessed to search for nonexperimental drugs evaluated in randomized clinical trials published in peer reviewed journals from January 1, 1970, to August 1, 2015, to reduce the number of recurrent UTIs in postmenopausal women. RESULTS: A systematic search yielded 9 articles that met eligibility criteria. Five articles involved the use of systemic or vaginal estrogen therapy and the remainder used oral antibiotics, lactobacilli, or a combination of interventions. Antibiotics were the most efficacious therapy but with a higher incidence of systemic side effects. Oral lactobacillus was noninferior to sulfamethoxazole with trimethoprim with a safer profile in 1 small study. Vaginal estrogen appeared to be inferior to continuous oral antibiotic suppression; however, use of multiple formulations of both treatment options precludes meta-analysis. Oral estrogen use did not decrease UTI recurrence and resulted in local and systemic side effects in up to nearly 30% of the patients. CONCLUSIONS: This review supports the use of antibiotic suppression, vaginal estrogen, and oral lactobacillus for prevention of recurrent UTIs in postmenopausal women. However, the overall dearth of data suggests that this is an important but understudied population. Because the effectiveness and safety of available treatments are not well understood, they should be used with caution in older populations, pending further study. PMID- 26825412 TI - Building a National Registry for Pelvic Organ Prolapse. PMID- 26825413 TI - Cultural differences in self-recognition: the early development of autonomous and related selves? AB - Fifteen- to 18-month-old infants from three nationalities were observed interacting with their mothers and during two self-recognition tasks. Scottish interactions were characterized by distal contact, Zambian interactions by proximal contact, and Turkish interactions by a mixture of contact strategies. These culturally distinct experiences may scaffold different perspectives on self. In support, Scottish infants performed best in a task requiring recognition of the self in an individualistic context (mirror self-recognition), whereas Zambian infants performed best in a task requiring recognition of the self in a less individualistic context (body-as-obstacle task). Turkish infants performed similarly to Zambian infants on the body-as-obstacle task, but outperformed Zambians on the mirror self-recognition task. Verbal contact (a distal strategy) was positively related to mirror self-recognition and negatively related to passing the body-as-obstacle task. Directive action and speech (proximal strategies) were negatively related to mirror self-recognition. Self-awareness performance was best predicted by cultural context; autonomous settings predicted success in mirror self-recognition, and related settings predicted success in the body-as-obstacle task. These novel data substantiate the idea that cultural factors may play a role in the early expression of self-awareness. More broadly, the results highlight the importance of moving beyond the mark test, and designing culturally sensitive tests of self-awareness. PMID- 26825415 TI - Screening and likelihood ratio infographic. PMID- 26825414 TI - The opioid effects of gluten exorphins: asymptomatic celiac disease. AB - Gluten-containing cereals are a main food staple present in the daily human diet, including wheat, barley, and rye. Gluten intake is associated with the development of celiac disease (CD) and related disorders such as diabetes mellitus type I, depression, and schizophrenia. However, until now, there is no consent about the possible deleterious effects of gluten intake because of often failing symptoms even in persons with proven CD. Asymptomatic CD (ACD) is present in the majority of affected patients and is characterized by the absence of classical gluten-intolerance signs, such as diarrhea, bloating, and abdominal pain. Nevertheless, these individuals very often develop diseases that can be related with gluten intake. Gluten can be degraded into several morphine-like substances, named gluten exorphins. These compounds have proven opioid effects and could mask the deleterious effects of gluten protein on gastrointestinal lining and function. Here we describe a putative mechanism, explaining how gluten could "mask" its own toxicity by exorphins that are produced through gluten protein digestion. PMID- 26825416 TI - Predictors of maternal health services utilization by poor, rural women: a comparative study in Indian States of Gujarat and Tamil Nadu. AB - BACKGROUND: India leads all nations in numbers of maternal deaths, with poor, rural women contributing disproportionately to the high maternal mortality ratio. In 2005, India launched the world's largest conditional cash transfer scheme, Janani Suraksha Yojana (JSY), to increase poor women's access to institutional delivery, anticipating that facility-based birthing would decrease deaths. Indian states have taken different approaches to implementing JSY. Tamil Nadu adopted JSY with a reorganization of its public health system, and Gujarat augmented JSY with the state-funded Chiranjeevi Yojana (CY) scheme, contracting with private physicians for delivery services. Given scarce evidence of the outcomes of these approaches, especially in states with more optimal health indicators, this cross sectional study examined the role of JSY/CY and other healthcare system and social factors in predicting poor, rural women's use of maternal health services in Gujarat and Tamil Nadu. METHODS: Using the District Level Household Survey (DLHS)-3, the sample included 1584 Gujarati and 601 Tamil rural women in the lowest two wealth quintiles. Multivariate logistic regression analyses examined associations between JSY/CY and other salient health system, socio-demographic, and obstetric factors with three outcomes: adequate antenatal care, institutional delivery, and Cesarean-section. RESULTS: Tamil women reported greater use of maternal healthcare services than Gujarati women. JSY/CY participation predicted institutional delivery in Gujarat (AOR = 3.9), but JSY assistance failed to predict institutional delivery in Tamil Nadu, where mothers received some cash for home births under another scheme. JSY/CY assistance failed to predict adequate antenatal care, which was not incentivized. All-weather road access predicted institutional delivery in both Tamil Nadu (AOR = 3.4) and Gujarat (AOR = 1.4). Women's education predicted institutional delivery and Cesarean-section in Tamil Nadu, while husbands' education predicted institutional delivery in Gujarat. CONCLUSIONS: Overall, assistance from health financing schemes, good road access to health facilities, and socio-demographic and obstetric factors were associated with differential use of maternity health services by poor, rural women in the two states. Policymakers and practitioners should promote financing schemes to increase access, including consideration of incentives for antenatal care, and address health system and social factors in designing state-level interventions to promote safe motherhood. PMID- 26825417 TI - Multi-institutional evaluation of the indications and radiation dose of functional cardiovascular computed tomography (CCT) imaging in congenital heart disease. AB - Ventricular volumes and ejection fraction are often used in clinical decision making in patients with congenital heart disease (CHD). The referral diagnosis, radiation exposure and image quality of functional cardiac computed tomography (CT) in a relatively large cohort of patients of CHD has not been reported. This is a retrospective evaluation of functional CT studies performed in CHD patients from three institutions (1/2007-3/2013). Patient and scanner characteristics, radiation dose estimates and image quality were compared. Two hundred ninety eight functional CT studies were evaluated. The most common referral diagnosis were tetralogy of Fallot (33 %), transposition complexes(24 %) single ventricle heart disease (15 %), and left sided obstruction (15 %). The reason for cardiac CT was presence of pacemaker (60 %), need for detailed coronary artery imaging (18 %), metallic artifact inC MR(12 %), evaluation of prosthetic valve function (4 %), and claustrophobia or BMI too large for the available MR scanner (6 %). 266(89.3 %) scans allowed quantification of ventricular function,25 (8.4 %) scans allowed qualitative assessment of function, and 7 (2.3 %) of the scans were non diagnostic for functional analysis. Median DLP was 399 mGy cm (186,614), and median effective dose was 5.5 mSv (2.6, 8.5).Radiation dose and image quality varied across institutions.Cardiac CT function imaging can be performed in patients with congenital heart disease when CMR is contraindicated or has poor image quality. Radiation dose and image quality varies across institutions. PMID- 26825418 TI - Re: 'Association between exclusive maternal breastfeeding during the first 4 months of life and primary enuresis'. PMID- 26825419 TI - Nancy Hirschberg (1937-1979). PMID- 26825420 TI - Factors In The Natural Language Of Personality: Re-Analysis, Comparison, And Interpretation Of Six Major Studies. AB - Psychometric studies of the organization of the "natural language of personality" have typically employed rating scales as measurement medium and factor analysis as statistical technique. The results of such investigations over the past 30 years have varied greatly, both with respect to number of factors and with respect to the constructs generated. Re-analysis of the correlations of six studies, including the classical work of Cattell, indicated that the domain appears to be well described by five factors, with some suggestion of a sixth. The five factors were related across studies, using the Kaiser-Hunka-Bianchini method. Generally, the factors were highly related, with most indices of relatedness exceeding .90. The five-factor model was tested by the multiple-group method, used to factor a large-scale study of teachers' ratings of children. With slight modification of the originally hypothesized structure, the five-factor model accounted for the observed relationships quite well. The five constructs suggested by the factors appear to be domains of research effort and theoretical concern which have long been of interest to psychologists. PMID- 26825421 TI - A Monte Carlo Investigation Of The Likelihood Ratio Test For The Number Of Components In A Mixture Of Normal Distributions. AB - A likelihood ratio test to determine whether data arises from a single or a mixture of two normal distributions is investigated by Monte Carlo methods. The results show that the proposed sampling distribution of the test appears to be appropriate only for sample sizes above fifty, and for data where the sample size is ten times the number of variables. For such cases the power of the test is considered and found to be fairly low unless the generalized distance between the components is greater than 2.0. PMID- 26825422 TI - Development Of Scales For Three Second-Order Factors Of Inner Experience. AB - Short 15 item scales are developed to measure three second-order factors found within the domain of inner experience, daydreaming, and fantasy encompassed by the Imaginal Processes Inventory. Scales are presented for Positive-Constructive Daydreaming, Guilt-Fear of Failure Daydreaming, and Poor Attentional Control. The measures are derived from a sequential factor analytic, discriminant/convergent validity process guided by accumulated theoretical knowledge in the fields of daydreaming and fantasy. The factor pattern of items is shown stable across sexes and then different ethnicity and sex groups are contrasted on the three second order factor scales. The distribution of daydreaming scores was also studied. PMID- 26825423 TI - Applying The Semistandardized Regression Coefficient To Factor, Canonical, And Path Analysis. AB - The semistandardized (SS) regression coefficient is applied to factor, canonical and path analysis. The SS regression coefficient is interpreted as: if the standardized independent factor, canonical variate, or variable increases one standard deviation unit, then the dependent indicator y will increase by b' yzx units. The SS coefficient provides information not given by the conventional standardized regression coefficients used in factor, canonical, and path analysis. PMID- 26825424 TI - The Multivariate Structure Of Design Evaluation: A Cylindrex of Nurses' Conceptualizations. AB - It is argued that facet theory provides an appropriate framework for examining the structure of the psychological evaluation of building designs. By means of a mapping sentence, a definitional system is provided for the universe of evaluations by nurses of the design and layout of the wards on which they work. A rationale is provided both for the facets and their elements within the mapping sentence, and for their anticipated role within an empirical structure. The structure predicted contains a facet concerning levels of interaction, which is axial to two further facets. One of these, dealing with the object of the nurses' interaction, plays a polarizing role, being modulated by the third facet, which concerns whether the object being interacted with provides patient care and comfort directly or indirectly. Taken together the three facets provide the hypothesis of a cylindrex for nurses' evaluations. Clear empirical evidence for the cylindrex is provided as a result of a three-dimensional smallest-space analysis carried out on the responses given by 1921 nurses in 144 wards in 23 hospitals throughout England to a 93-item questionnaire developed as the result of a series of three pilot questionnaires. The implications of the cylindrex for future research and the development of design proposals are discussed. PMID- 26825425 TI - Associations Between Violent And Nonviolent Criminality: A Canonical Contingency Table Analysis. AB - Frequencies of violent and nonviolent convictions among 390 adult, male offenders were cross-tabulated, dummy coded, and analyzed by canonical correlation. Though of small magnitude, a statistically significant dimension of association between violent and nonviolent criminality was obtained, and the nature of this relationship was ascertained by means of intraset and interset structure coefficients and an index of interset redundancy. The results, weakly supportive of the crime specialization hypothesis, were seen to illustrate the potential usefulness of a canonical correlational approach to the analysis of a two-way contingency table. PMID- 26825426 TI - Multivariate ATI Analysis. AB - Analysis of multivariate aptitude-treatment-interaction data is discussed. Various global hypotheses and the associated follow-up descriptions are considered and compared. Analysis procedures are illustrated using data from a science education study to describe the interaction between student reading ability and the time allowed in an individualized instructional approach for multiple achievement and attitudinal outcomes. PMID- 26825427 TI - Movement kinematics and cyclic fatigue of NiTi rotary instruments: a systematic review. AB - The aim of this review was to provide a detailed analysis of the literature concerning the correlation between different movement kinematics and the cyclic fatigue resistance of NiTi rotary endodontic instruments. From June 2014 to August 2015, four independent reviewers comprehensively and systematically searched the Medline (PubMed), EMBASE, Web of Science, Scopus and Google Scholar databases for works published since January 2005, using the following search terms: endodontics; nickel-titanium rotary files; continuous rotation; reciprocating motion; cyclic fatigue. In addition to the electronic searches, manual searches were performed to include articles listed in the reference sections of high-impact published articles that were not indexed in the databases. Laboratory studies in English language were considered for this review. The electronic and manual searches resulted in identification of 75 articles. Based on the inclusion criteria, 32 articles were selected for analysis of full-text copies. Specific analysis was then made of 20 articles that described the effects of reciprocating and continuous movements on cyclic fatigue of the instruments. A wide range of testing conditions and methodologies have been used to compare the cyclic fatigue resistance of rotary endodontic instruments. Most studies report that reciprocating motion improves the fatigue resistance of endodontic instruments, compared to continuous rotation, independent of other variables such as the speed of rotation, the angle or radius of curvature of simulated canals, geometry and taper, or the surface characteristics of the NiTi instruments. PMID- 26825428 TI - Conservation as vaccination: Integrated approaches to public health and environmental protection could prevent future disease outbreaks. PMID- 26825429 TI - Exercise and Fall Prevention: Narrowing the Research-to-Practice Gap and Enhancing Integration of Clinical and Community Practice. AB - Falls in older adults are a global public health crisis, but mounting evidence from randomized controlled trials shows that falls can be reduced through exercise. Public health authorities and healthcare professionals endorse the use of evidence-based, exercise-focused fall interventions, but there are major obstacles to translating and disseminating research findings into healthcare practice, including lack of evidence of the transferability of efficacy trial results to clinical and community settings, insufficient local expertise to roll out community exercise programs, and inadequate infrastructure to integrate evidence-based programs into clinical and community practice. The practical solutions highlighted in this article can be used to address these evidence-to practice challenges. Falls and their associated healthcare costs can be reduced by better integrating research on exercise intervention into clinical practice and community programs. PMID- 26825430 TI - Evaluation of In Vivo Osteogenic Potential of Bone Morphogenetic Protein 2 Overexpressing Human Periodontal Ligament Stem Cells Combined with Biphasic Calcium Phosphate Block Scaffolds in a Critical-Size Bone Defect Model. AB - Human periodontal ligament stem cells (hPDLSCs) are considered potential cellular carriers for gene delivery in the field of tissue regeneration. This study tested the osseoregenerative potential of hPDLSCs transduced with replication-deficient recombinant adenovirus (rAd) containing the gene encoding bone morphogenetic protein-2 (BMP2; hPDLSCs/rAd-BMP2) in both in vivo and in vitro osteogenic environments. After the optimal condition for rAd-mediated transduction was determined, hPDLSCs were transduced to express BMP2. In vivo bone formation was evaluated in a critical-size rat calvarial bone defect model that more closely mimics the harsher in vivo milieu for bone regeneration than subcutaneous transplantation model. As support materials for bone regeneration, block-type biphasic calcium phosphate (BCP) scaffolds were combined with hPDLSCs and/or BMP2 and transplanted into critical-size bone defects in rats. Experimental groups were as follows: BCP scaffold control (group 1 [Gr1]), scaffold containing recombinant human BMP2 (rhBMP2; group 2 [Gr2]), scaffold loaded with normal hPDLSCs (group 3 [Gr3]), scaffold combined with both normal hPDLSCs and rhBMP2 (group 4 [Gr4]), and scaffold loaded with hPDLSCs transduced with rAd-BMP2 (hPDLSCs/rAd-BMP2; group 5 [Gr5]). Our data showed that new bone formation was highest in Gr2. Less mineralization was observed in Gr3, Gr4, and Gr5 in which hPDLSCs were transplanted. In vitro transwell assay demonstrated that hPDLSCs exert an inhibitory activity on BMP2-induced osteogenic differentiation. Our findings suggest that the in vivo bone regenerative potential of BMP2 overexpressing hPDLSCs could be compromised in a critical-size rat calvarial bone defect model. Thus, further investigations are required to elucidate the underlying mechanisms and to develop efficient techniques for improved tissue regeneration. PMID- 26825431 TI - Genomic survey provides insights into the evolutionary changes that occurred during European expansion of the invasive mosquitofish (Gambusia holbrooki). AB - Biological invasions rank among the main global threats for biodiversity. The Eastern mosquitofish (Gambusia holbrooki) is considered one of the 100 world worst invasive species due to its high adaptation capability to new environments. Using the restriction-site-associated DNA tags (RADtags), introduced European locations were compared against native US mosquitofish populations to analyse genomic changes that occurred during invasive process of European locations. After filtering, 7724 RADtags containing only one SNP were retained for population studies. Comparative genomics indicated that 186 of these RADtags matched sequences in the transcriptome of Xyphophorus maculatus, the most closely related genome available. Genomic analyses showed that invasive populations show high reductions in diversity. Further, analyses of population structuring based on these data are concordant with previous analyses based on microsatellites. It is concluded that during the invasion process genetic drift was the main evolutionary force affecting patterns of diversity and population structure. While recognizing that positive selection could be masked by the strong drift during founder events, adaptive processes were evidenced in a reduced number of RADtags (<2%), with only one of these in a putative coding region. Surprisingly, balancing selection was detected in several coding RADtags, suggesting that the preservation of polymorphism in specific genes could be more important than the average population diversity for the population maintenance at any location, particularly for the survival of introduced populations. PMID- 26825432 TI - Nebivolol ameliorates asymmetric dimethylarginine-induced vascular response in rat aorta via beta3 adrenoceptor-mediated mechanism. AB - BACKGROUND: Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, induces endothelial dysfunction. Nebivolol, a highly selective beta1-adrenergic receptor (AR) blocker, is the only beta-blocker known to induce vascular production of nitric oxide. OBJECTIVE: The present study was designed to evaluate the effect and mechanism of nebivolol on ADMA-induced vascular response in rat aorta in vitro. METHODS: In vitro, the effects of nebivolol and ADMA on resting tone or contraction induced by phenylephrine (PE, 10(-6 )mol/L) and relaxation induced by acetylcholine (Ach, 10(-10)-10(-5 )mol/L) were evaluated. RESULTS: ADMA in a concentration-dependent manner increased the resting and PE-induced tone and reduced Ach-induced relaxation. Nebivolol inhibited the ADMA-induced enhancements in tone and reversed the effects of ADMA on Ach-induced relaxation. These effects of nebivolol were blocked by selective beta3 receptor blocker cyanopindolol (1 MUM), but not by selective beta2 receptor blocker butoxamine (50 MUM). CONCLUSIONS: Nebivolol ameliorates the ADMA-induced vascular responses in rat aorta, at least in part, by mechanisms involving beta3 adrenoceptor. PMID- 26825433 TI - Extracorporeal life support during pregnancy. AB - OBJECTIVES: To review the literature on extracorporeal life support (ECLS) during pregnancy to determine its efficacy and safety for the mother and fetus. METHODS: A comprehensive literature search was obtained from MEDLINE via PubMed.gov and from ScienceDirect.com using the following search queries: ECLS and pregnancy, extracorporeal membrane oxygenation (ECMO) and pregnancy, ECMO and H1N1 influenza, acute respiratory distress syndrome (ARDS) and pregnancy, pregnancy and H1N1 influenza, and Extracorporeal Life Support Organization registry. RESULTS: Our literature search produced 332 articles for review. A total of 45 patients treated with ECLS or ECMO during pregnancy were reported in 26 publications. Postpartum patients were not included. Indications for ECLS were severe H1N1 influenza with ARDS (n = 33), other ARDS (n = 8), cardiogenic shock (n = 3), and cardiac arrest (n = 1). The mean gestational age was 26.5 weeks (range, 12-38 weeks), and the median duration of ECLS was 12.2 days (range, 1-57 days). The survival rate was 77.8% (35 of 45) for mothers and 65.1% (28 of 43) for fetuses. In addition, we report a 25-year-old pregnant patient with hantavirus cardiopulmonary syndrome unresponsive to pressors and inotropes. The patient was placed on venoarterial ECMO for 72 hours, recovered without complications, and delivered a healthy infant. The mother and son remain asymptomatic 6 years later. CONCLUSIONS: ECLS during pregnancy is effective and relatively safe for the mother and fetus. The first successful use of ECLS in a pregnant patient with life-threatening hantavirus cardiopulmonary syndrome is being reported together with this review. PMID- 26825434 TI - Characteristics and long-term outcomes of contemporary patients with bicuspid aortic valves. AB - BACKGROUND: We sought to study the impact of surgical intervention on long-term outcomes in bicuspid aortic valve (BAV) patients who develop aortic valvular complications and/or have a concomitant aortopathy. METHODS: We studied 1890 consecutive patients with BAV (age 50 +/- 14 years; 75% men), evaluated in the time period 2003 to 2007. Clinical and imaging data were recorded. The endpoint was a composite of death or type A aortic dissection. RESULTS: The mean left ventricular ejection fraction was 55% +/- 8%; 31% had New York Heart Association class >= III aortic regurgitation, and 17% had mean aortic valve (AV) gradient >=30 mm Hg. Dilated (>=4 cm) aortic root and ascending aorta were observed in 35% and 42% of patients, respectively. At 8.1 +/- 2 years, 918 (49%) patients underwent surgery (883 had AV replacement and/or repair (+/- combination procedures), 471 with ascending aortic grafting (30 had isolated aortic grafting), and 171 (9%) events (169 deaths and 2 dissections) occurred; 0.4% was the 30-day mortality). On multivariable Cox survival analysis, increasing age (hazard ratio [HR] 1.06, 95% confidence interval [CI] [1.05-1.07]), increasing aortic root size (HR 1.32, 95% CI [1.07-1.65]), decreasing LV ejection fraction (HR 1.04, 95% CI [1.03-1.05]), and hyperlipidemia (HR 1.51, 95% CI [1.20-1.89]) had higher associated events, and surgery related to BAV (time-dependent covariate) (HR 0.44, 95% CI [0.31-0.70]) was associated with significantly lower events (all P < .01). Addition of surgery to BAV risk score (a composite of age, >=moderate-severe aortic stenosis or regurgitation) and aortic root size further improved risk stratification (the C-statistic increased from 0.65 to 0.73; P = .01). CONCLUSIONS: Patients with BAV have a high prevalence of AV dysfunction and concomitant aortopathy. Undergoing surgery (AV replacement and/or repair +/- AAR) was associated with a significantly lower incidence of death and/or dissection. PMID- 26825435 TI - Rare life-threatening complication of device closure of ventricular septal defect in a child. PMID- 26825436 TI - Diabetic foot risk assessment. AB - Diabetes is a serious chronic disease that results in foot complications for many people world-wide. In 2014, the World Health Organization estimated the global prevalence of diabetes in adults to be 9%. To ascertain the risk that an individual patient might develop a diabetic foot ulcer that could lead to an amputation, clinicians are strongly encouraged to perform a risk assessment. Monteiro-Soares and Dinis-Ribeiro have presented a new DIAbetic FOot Risk Assessment with the acronym DIAFORA. It is different from other risk assessments in that it predicts the risk of developing both diabetic foot ulcers and amputation specifically. The risk variables were derived by regression analysis based on a data set of 293 patients from a high-risk setting, a Hospital Diabetic Foot Clinic, who had diabetes and a diabetic foot ulcers. Clear descriptions of the risk variables are provided as well as sensitivity, specificity, positive and negative predictive values for the risk categories. As an added benefit, likelihood ratios are provided that will help clinicians determine the risk of amputation for individual patients. Having a risk assessment form is important for clinician use and examples exist. A question is raised about the effectiveness of risk assessment and how effectiveness might be determined. PMID- 26825437 TI - Neural representation of object-specific attentional priority. AB - Humans can flexibly select locations, features, or objects in a visual scene for prioritized processing. Although it is relatively straightforward to manipulate location- and feature-based attention, it is difficult to isolate object-based selection. Because objects are always composed of features, studies of object based selection can often be interpreted as the selection of a combination of locations and features. Here we examined the neural representation of attentional priority in a paradigm that isolated object-based selection. Participants viewed two superimposed gratings that continuously changed their color, orientation, and spatial frequency, such that the gratings traversed the same exact feature values within a trial. Participants were cued at the beginning of each trial to attend to one or the other grating to detect a brief luminance increment, while their brain activity was measured with fMRI. Using multi-voxel pattern analysis, we were able to decode the attended grating in a set of frontoparietal areas, including anterior intraparietal sulcus (IPS), frontal eye field (FEF), and inferior frontal junction (IFJ). Thus, a perceptually varying object can be represented by patterned neural activity in these frontoparietal areas. We suggest that these areas can encode attentional priority for abstract, high-level objects independent of their locations and features. PMID- 26825438 TI - Computational substrates of social norm enforcement by unaffected third parties. AB - Enforcement of social norms by impartial bystanders in the human species reveals a possibly unique capacity to sense and to enforce norms from a third party perspective. Such behavior, however, cannot be accounted by current computational models based on an egocentric notion of norms. Here, using a combination of model based fMRI and third party punishment games, we show that brain regions previously implicated in egocentric norm enforcement critically extend to the important case of norm enforcement by unaffected third parties. Specifically, we found that responses in the ACC and insula cortex were positively associated with detection of distributional inequity, while those in the anterior DLPFC were associated with assessment of intentionality to the violator. Moreover, during sanction decisions, the subjective value of sanctions modulated activity in both vmPFC and rTPJ. These results shed light on the neurocomputational underpinnings of third party punishment and evolutionary origin of human norm enforcement. PMID- 26825440 TI - Modelling the perceptual similarity of facial expressions from image statistics and neural responses. AB - The ability to perceive facial expressions of emotion is essential for effective social communication. We investigated how the perception of facial expression emerges from the image properties that convey this important social signal, and how neural responses in face-selective brain regions might track these properties. To do this, we measured the perceptual similarity between expressions of basic emotions, and investigated how this is reflected in image measures and in the neural response of different face-selective regions. We show that the perceptual similarity of different facial expressions (fear, anger, disgust, sadness, happiness) can be predicted by both surface and feature shape information in the image. Using block design fMRI, we found that the perceptual similarity of expressions could also be predicted from the patterns of neural response in the face-selective posterior superior temporal sulcus (STS), but not in the fusiform face area (FFA). These results show that the perception of facial expression is dependent on the shape and surface properties of the image and on the activity of specific face-selective regions. PMID- 26825439 TI - One of the most well-established age-related changes in neural activity disappears after controlling for visual acuity. AB - Numerous studies using a variety of imaging techniques have reported age-related differences in neural activity while subjects carry out cognitive tasks. Surprisingly little attention has been paid to the potential impact of age associated changes in sensory acuity on these findings. Studies in the visual modality frequently report that their subjects had "normal or corrected- to normal vision." However, in most cases, there is no indication that visual acuity was actually measured, and it is likely that the investigators relied largely on self-reported visual status of subjects, which is often inaccurate. We investigated whether differences in visual acuity influence one of the most commonly observed findings in the event-related potentials literature on cognitive aging, a reduction in posterior P3b amplitude, which is an index of cognitive decision-making/updating. Well-matched young (n=26) and old adults (n=29) participated in a visual oddball task. Measured visual acuity with corrective lenses was worse in old than young adults. Results demonstrated that the robust age-related decline in P3b amplitude to visual targets disappeared after controlling for visual acuity, but was unaffected by accounting for auditory acuity. Path analysis confirmed that the relationship between age and diminished P3b to visual targets was mediated by visual acuity, suggesting that conveyance of suboptimal sensory data due to peripheral, rather than central, deficits may undermine subsequent neural processing. We conclude that until the relationship between age-associated differences in visual acuity and neural activity during experimental tasks is clearly established, investigators should exercise caution attributing results to differences in cognitive processing. PMID- 26825441 TI - Traffic pollution exposure is associated with altered brain connectivity in school children. AB - Children are more vulnerable to the effects of environmental elements due to their active developmental processes. Exposure to urban air pollution has been associated with poorer cognitive performance, which is thought to be a result of direct interference with brain maturation. We aimed to assess the extent of such potential effects of urban pollution on child brain maturation using general indicators of vehicle exhaust measured in the school environment and a comprehensive imaging evaluation. A group of 263 children, aged 8 to 12 years, underwent MRI to quantify regional brain volumes, tissue composition, myelination, cortical thickness, neural tract architecture, membrane metabolites, functional connectivity in major neural networks and activation/deactivation dynamics during a sensory task. A combined measurement of elemental carbon and NO2 was used as a putative marker of vehicle exhaust. Air pollution exposure was associated with brain changes of a functional nature, with no evident effect on brain anatomy, structure or membrane metabolites. Specifically, a higher content of pollutants was associated with lower functional integration and segregation in key brain networks relevant to both inner mental processes (the default mode network) and stimulus-driven mental operations. Age and performance (motor response speed) both showed the opposite effect to that of pollution, thus indicating that higher exposure is associated with slower brain maturation. In conclusion, urban air pollution appears to adversely affect brain maturation in a critical age with changes specifically concerning the functional domain. PMID- 26825442 TI - Alterations of functional connectivities from early to middle adulthood: Clues from multivariate pattern analysis of resting-state fMRI data. AB - In contrast to extended research interests in the maturation and aging of human brain, alterations of brain structure and function from early to middle adulthood have been much less studied. The aim of the present study was to investigate the extent and pattern of the alterations of functional interactions between brain regions from early to middle adulthood. We carried out the study by multivariate pattern analysis of resting-state fMRI (RS-fMRI) data of 63 adults aged 18 to 45 years. Specifically, using elastic net, we performed brain age estimation and age group classification (young adults aged 18-28 years vs. middle-aged adults aged 35-45 years) based on the resting-state functional connectivities (RSFCs) between 160 regions of interest (ROIs) evaluated on the RS-fMRI data of each subject. The results indicate that the estimated brain ages were significantly correlated with the chronological age (R=0.78, MAE=4.81), and a classification rate of 94.44% and area under the receiver operating characteristic curve (AUC) of 0.99 were obtained when classifying the young and middle-aged adults. These results provide strong evidence that functional interactions between brain regions undergo notable alterations from early to middle adulthood. By analyzing the RSFCs that contribute to brain age estimation/age-group classification, we found that a majority of the RSFCs were inter-network, and we speculate that inter-network RSFCs might mature late but age early as compared to intra-network ones. In addition, the strengthening/weakening of the RSFCs associated with the left/right hemispheric ROIs, the weakening of cortico-cerebellar RSFCs and the strengthening of the RSFCs between the default mode network and other networks contributed much to both brain age estimation and age-group classification. All these alterations might reflect that aging of brain function is already in progress in middle adulthood. Overall, the present study indicated that the RSFCs undergo notable alterations from early to middle adulthood and highlighted the necessity of careful considerations of possible influences of these alterations in related studies. PMID- 26825443 TI - Modulation of frontal effective connectivity during speech. AB - Noninvasive neurostimulation methods such as transcranial direct current stimulation (tDCS) can elicit long-lasting, polarity-dependent changes in neocortical excitability. In a previous concurrent tDCS-fMRI study of overt picture naming, we reported significant behavioural and regionally specific neural facilitation effects in left inferior frontal cortex (IFC) with anodal tDCS applied to left frontal cortex (Holland et al., 2011). Although distributed connectivity effects of anodal tDCS have been modelled at rest, the mechanism by which 'on-line' tDCS may modulate neuronal connectivity during a task-state remains unclear. Here, we used Dynamic Causal Modelling (DCM) to determine: (i) how neural connectivity within the frontal speech network is modulated during anodal tDCS; and, (ii) how individual variability in behavioural response to anodal tDCS relates to changes in effective connectivity strength. Results showed that compared to sham, anodal tDCS elicited stronger feedback from inferior frontal sulcus (IFS) to ventral premotor (VPM) accompanied by weaker self connections within VPM, consistent with processes of neuronal adaptation. During anodal tDCS individual variability in the feedforward connection strength from IFS to VPM positively correlated with the degree of facilitation in naming behaviour. These results provide an essential step towards understanding the mechanism of 'online' tDCS paired with a cognitive task. They also identify left IFS as a 'top-down' hub and driver for speech change. PMID- 26825445 TI - Anticoagulation therapy in elderly patients with atrial fibrillation: results from the Registry of Atrial Fibrillation To Investigate the Implementation of New Guidelines (RAFTING). AB - BACKGROUND: Patients with atrial fibrillation aged 75 years or older have a CHA2DS2VASc score that dictates oral anticoagulants. We recorded physicians' anticoagulation attitudes in elderly patients with atrial fibrillation and assessed the impact of stroke and bleeding risk. METHODS: Atrial Fibrillation To Investigate the Implementation of New Guidelines , a countrywide prospective registry performed in Greece during 2010, a period when only vitamin-K antagonists (VKA) were available, enrolled 1127 patients with atrial fibrillation diagnosis during Emergency Departments visit in 31 representative hospitals; 807 patients had known atrial fibrillation and of those, 342 aged 75 years or older. We recorded preadmission anticoagulation treatment and associated it with clinical characteristics and stroke/bleeding risk. RESULTS: Patients on VKA (n = 207; 61%) were younger (81 +/- 4 vs. 83 +/- 5; P < 0.001) but no other significant differences were noticed, including mean CHA2DS2VASc (high: 2-4, very high: >4) or modified HASBLED (low: 0-2, high: >2) scores. VKA were prescribed in 65% of patients with very high CHA2DS2VASc score as compared with 55% of those with high score (P = 0.065). VKA were used equally in low or high-modified HASBLED score (61% vs. 59%; P = 0.78). The interaction between CHA2DS2VASc and HASBLED was significant (P < 0.001) in patients on VKA; in patients with low HASBLED, VKA use was similar in high versus very high CHA2DS2VASc score (58 vs. 64%), whereas in patients with high HASBLED, VKA use tended to be higher in very high versus high CHA2DS2VASc score (66 vs. 43%). CONCLUSION: In this countrywide atrial fibrillation registry, 61% of elderly patients received VKA, a decision driven mainly by stroke risk. VKA use was not higher in patients with low bleeding risk. PMID- 26825444 TI - Analysis of two TFL1 homologs of dogwood species (Cornus L.) indicates functional conservation in control of transition to flowering. AB - MAIN CONCLUSION: Two TFL1 -like genes, CorfloTFL1 and CorcanTFL1 cloned from Cornus florida and C. canadensis, function in regulating the transition to reproductive development in Arabidopsis. TERMINAL FLOWER 1 (TFL1) is known to regulate inflorescence development in Arabidopsis thaliana and to inhibit the transition from a vegetative to reproductive phase within the shoot apical meristem. Despite the importance, TFL1 homologs have been functionally characterized in only a handful eudicots. Here we report the role of TFL1 homologs of Cornus L. in asterid clade of eudicots. Two TFL1-like genes, CorfloTFL1 and CorcanTFL1, were cloned from Cornus florida (a tree) and C. canadensis (a subshrub), respectively. Both are deduced to encode proteins of 175 amino acids. The amino acid sequences of these two Cornus TFL1 homologs share a high similarity to Arabidopsis TFL1 and phylogenetically more close to TFL1 paralogous copy ATC (Arabidopsis thaliana CENTRORADIALIS homologue). Two genes are overexpressed in wild-type and tfl1 mutant plants of A. thaliana. The over expression of each gene in wild-type Arabidopsis plants results in delaying flowering time, increase of plant height and cauline and rosette leaf numbers, excessive shoot buds, and secondary inflorescence branches. The over-expression of each gene in the tfl1 mutant rescued developmental defects, such as the early determinate inflorescence development, early flowering time, and other vegetative growth defects, to normal phenotypes of wild-type plants. These transgenic phenotypes are inherited in progenies. All data indicate that CorfloTFL1 and CorcanTFL1 have conserved the ancestral function of TFL1 and CEN regulating flowering time and inflorescence determinacy. PMID- 26825446 TI - BleeMACS: rationale and design of the study. AB - BACKGROUND: Bleeding events after an acute coronary syndrome have a negative impact on prognosis. Available risk scores are limited by suboptimal accuracy, prediction of only in-hospital events and absence of patients treated with new antiplatelet agents in the current era of widespread use of percutaneous coronary intervention. DESIGN: The BleeMACS (Bleeding complications in a Multicenter registry of patients discharged after an Acute Coronary Syndrome) project is a multicenter investigator-initiated international retrospective registry that enrolled more than 15 000 patients discharged with a definitive diagnosis of acute coronary syndrome and treated with percutaneous revascularization. The primary end point is the incidence of major bleeding events requiring hospitalization and/or red cell transfusion concentrates within 1 year. An integer risk score for bleeding within the first year after hospital discharge will be developed from a multivariate competing-risks regression. CONCLUSION: The BleeMACS registry collaborative will allow development and validation of a risk score for prediction of major bleeding during follow-up for patients receiving contemporary therapies for acute coronary syndrome. PMID- 26825447 TI - Effects of exposure to carbon dioxide and bioeffluents on perceived air quality, self-assessed acute health symptoms, and cognitive performance. AB - The purpose of this study was to examine the effects on humans of exposure to carbon dioxide (CO2 ) and bioeffluents. In three of the five exposures, the outdoor air supply rate was high enough to remove bioeffluents, resulting in a CO2 level of 500 ppm. Chemically pure CO2 was added to this reference condition to create exposure conditions with CO2 at 1000 or 3000 ppm. In two further conditions, the outdoor air supply rate was restricted so that the bioeffluent CO2 reached 1000 or 3000 ppm. The same 25 subjects were exposed for 255 min to each condition. Subjective ratings, physiological responses, and cognitive performance were measured. No statistically significant effects on perceived air quality, acute health symptoms, or cognitive performance were seen during exposures when CO2 was added. Exposures to bioeffluents with CO2 at 3000 ppm reduced perceived air quality; increased the intensity of reported headache, fatigue, sleepiness, and difficulty in thinking clearly; and reduced speed of addition, the response time in a redirection task, and the number of correct links made in the cue-utilization test. This suggests that moderate concentrations of bioeffluents, but not pure CO2 , will result in deleterious effects on occupants during typical indoor exposures. PMID- 26825448 TI - Parent Attributions About Child Symptoms Related to Cancer Therapy. AB - PURPOSE: Symptom assessment is an emergent area of research in pediatric cancer. Our team previously reported on the development of a questionnaire to be completed by parents to determine symptom prevalence and bother. This exploratory study examined parental nonprobed, free-text comments about their child's treatment-related symptoms reported on the questionnaire. METHOD: Participants were parents of children aged 4 to 18 years who had been diagnosed with cancer at least 2 months prior to enrolment and had received intravenous chemotherapy within the past month at 1 of 5 pediatric cancer centers. The questionnaire consisted of 69 or 71 items (based on child's age) addressing physical and psychological sequelae. Each symptom query was accompanied by a blank space in which parents could comment on their response. Comments were analyzed guided by content analysis methodology. RESULTS: Five major themes emerged: parental attributions for the symptoms experienced in their child; coping patterns and communication styles within the family; evidence of anticipatory, procedural, and other anxieties; interruption of daily life; and changes in the child's physical appearance. CONCLUSIONS: These exploratory findings provide context to parental perception of their child's treatment-related symptoms and may contribute to a better understanding of parental perception of child and the family coping and communicating style. These findings may assist in the development of psychoeducational interventions aimed at promoting open communication styles within the family and reducing child and parent burden during treatment procedures. PMID- 26825449 TI - Unintentional childhood injury: a controlled comparison of behavioral characteristics. AB - BACKGROUND: Childhood injury is a major public health problem around the world and those injuries have negative impacts on children and their families. The purpose of this study was to compare the behavioral characteristics between Chinese school-age children (6 to 11 years of age) with and without unintentional injuries and to identify behavioral risk factors for school-age children with unintentional injury. METHODS: This cross-sectional predictive study was conducted in five elementary schools in Daqing, China. The Achenbach Child Behavior Checklist (CBCL) was used to assess the children's behavioral characteristics. A total of 725 school-age children were screened. Of these, 116 children who had experienced unintentional injury in the past year were recruited as the study group, and 123 children who had not experienced an unintentional injury were randomly selected and assigned to the control group. RESULTS: The total scores of CBCL in the study group children were significantly higher than those in the control group. The significant behavior disorder predictors for unintentional injury in boys were schizoid behavior problem (OR = 2.43), anxiety/depression (OR = 2.76) and hyperactive (OR = 2.42). The predictors for unintentional injury in girls were anxiety/depression (OR = 2.12) and delinquent behavior (OR = 2.81). CONCLUSIONS: Children with behavior disorders are more likely to suffer from unintentional injuries. Teachers and pediatricians should identify the behavior disorders and assist parents to help children, thereby reducing the rate and severity of injuries. PMID- 26825450 TI - Three-dimensional flow in Kupffer's Vesicle. AB - Whilst many vertebrates appear externally left-right symmetric, the arrangement of internal organs is asymmetric. In zebrafish, the breaking of left-right symmetry is organised by Kupffer's Vesicle (KV): an approximately spherical, fluid-filled structure that begins to form in the embryo 10 hours post fertilisation. A crucial component of zebrafish symmetry breaking is the establishment of a cilia-driven fluid flow within KV. However, it is still unclear (a) how dorsal, ventral and equatorial cilia contribute to the global vortical flow, and (b) if this flow breaks left-right symmetry through mechanical transduction or morphogen transport. Fully answering these questions requires knowledge of the three-dimensional flow patterns within KV, which have not been quantified in previous work. In this study, we calculate and analyse the three dimensional flow in KV. We consider flow from both individual and groups of cilia, and (a) find anticlockwise flow can arise purely from excess of cilia on the dorsal roof over the ventral floor, showing how this vortical flow is stabilised by dorsal tilt of equatorial cilia, and (b) show that anterior clustering of dorsal cilia leads to around 40 % faster flow in the anterior over the posterior corner. We argue that these flow features are supportive of symmetry breaking through mechano-sensory cilia, and suggest a novel experiment to test this hypothesis. From our new understanding of the flow, we propose a further experiment to reverse the flow within KV to potentially induce situs inversus. PMID- 26825451 TI - [Not Available]. PMID- 26825452 TI - Distribution and determinants of young child feeding practices in the East African region: demographic health survey data analysis from 2008-2011. AB - We utilized the most recent Demographic Health Survey data to explore the distribution of feeding practices and examine relationships between complementary feeding and socio-demographic and health behaviour indicators in Kenya, Uganda and Tanzania. We based our analysis on complementary dietary diversity scores calculated for children 6-23 months old. Geographically, Kenya displayed clear division of children's diet diversity scores across its regions, unlike Uganda and Tanzania. Less than 40% of the children's meal frequencies in Uganda and Tanzania had met the minimum daily recommended levels. Only 30-40% of children in Kenya, Tanzania and Uganda had consumed diets with adequate diversity. Children's age, breastfeeding status, mother's education level and working status, household wealth index, prenatal care visits, receiving vitamin A supplements, using modern contraceptives and meal frequencies were significantly associated with adequate complementary food diversity in at least one of the three countries included in the current analyses. These analyses contribute to a better understanding and targeting of infant and young child feeding within the East African region. PMID- 26825453 TI - Bee Venom Accelerates Wound Healing in Diabetic Mice by Suppressing Activating Transcription Factor-3 (ATF-3) and Inducible Nitric Oxide Synthase (iNOS) Mediated Oxidative Stress and Recruiting Bone Marrow-Derived Endothelial Progenitor Cells. AB - Multiple mechanisms contribute to impaired diabetic wound healing including impaired neovascularization and deficient endothelial progenitor cell (EPC) recruitment. Bee venom (BV) has been used as an anti-inflammatory agent for the treatment of several diseases. Nevertheless, the effect of BV on the healing of diabetic wounds has not been studied. Therefore, in this study, we investigated the impact of BV on diabetic wound closure in a type I diabetic mouse model. Three experimental groups were used: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice treated with BV. We found that the diabetic mice exhibited delayed wound closure characterized by a significant decrease in collagen production and prolonged elevation of inflammatory cytokines levels in wounded tissue compared to control non-diabetic mice. Additionally, wounded tissue in diabetic mice revealed aberrantly up-regulated expression of ATF-3 and iNOS followed by a marked elevation in free radical levels. Impaired diabetic wound healing was also characterized by a significant elevation in caspase-3, -8, and -9 activity and a marked reduction in the expression of TGF beta and VEGF, which led to decreased neovascularization and angiogenesis of the injured tissue by impairing EPC mobilization. Interestingly, BV treatment significantly enhanced wound closure in diabetic mice by increasing collagen production and restoring the levels of inflammatory cytokines, free radical, TGF beta, and VEGF. Most importantly, BV-treated diabetic mice exhibited mobilized long-lived EPCs by inhibiting caspase activity in the wounded tissue. Our findings reveal the molecular mechanisms underlying improved diabetic wound healing and closure following BV treatment. J. Cell. Physiol. 231: 2159-2171, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26825454 TI - A mini-open technique for Achilles tenotomy in infants with clubfoot. AB - PURPOSE: A tendoachilles lengthening (TAL) is indicated in over 85 % of cases treated with the Ponseti technique. A percutaneous TAL is often performed in the clinic. Reported complications from a TAL performed in the clinic include: bleeding due to injury to the peroneal artery, posterior tibial artery, or lesser saphenous vein; injury to the tibial or sural nerves; and incomplete release. The purpose of the present study is to report the results and complications of a mini open TAL performed in the operating room (OR). METHODS: The current study is a retrospective review performed among infants with idiopathic clubfoot who underwent a mini-open TAL from 2008 to 2015. RESULTS: Forty-one patients underwent 63 TALs via a mini-open technique in day surgery. The average Pirani score was 5.8 prior to casting. The average number of casts applied prior to surgery was 5.2. The average age at the time of the TAL was 12.5 weeks (range 5 48 weeks). The average weight at the time of surgery was 7.3 kg (range 3.6-13 kg). No child had a delay in discharge or stayed overnight in the hospital. No anesthesia-related complications or neurovascular injuries occurred. No child needed a repeat TAL due to an incomplete tenotomy. CONCLUSIONS: In conclusion, mini-open TAL performed in the OR is safe and effective in infants with clubfeet. No complications occurred and all patients were discharged on the day of surgery. Direct visualization of the Achilles tendon via a mini-open technique minimizes the risk of neurovascular injury and incomplete tenotomy. PMID- 26825455 TI - The efficacy and short-term effects of electronic cigarettes as a method for smoking cessation: a systematic review and a meta-analysis. AB - OBJECTIVES: E-cigarettes are increasingly popular as smoking cessation aids. This review assessed the efficacy of e-cigarettes for smoking cessation as well as desire to smoke, withdrawal symptoms, and adverse events in adult smokers. METHODS: A systematic review was conducted. Studies comparing e-cigarettes to other nicotine replacement therapies or placebo were included. Data were pooled using meta-analysis. RESULTS: Of 569 articles, 5 were eligible. Study participants were more likely to stop smoking when using nicotine e-cigarettes (43/489, 9 %) versus placebo e-cigarettes (8/173, 5 %); however, this difference was not statistically significant (RR 2.02; 95 % CI 0.97, 4.22). The pooled effect estimates for the desire to smoke (RR -0.22; 95 % CI -0.80, 0.36), irritability (RR -0.03; 95% CI -0.38, 0.31), restlessness (RR -0.03; 95 % CI 0.42, 0.35), poor concentration (RR -0.01; 95 % CI -0.35, 0.32), depression (RR 0.01; 95 % CI -0.22, 0.20), hunger (RR -0.01; 95 % CI -0.32, 0.30), and average number of non-serious adverse events (RR -0.09; 95 % CI -0.28, 0.46) were not statistically significantly different. Only one study reported serious adverse events with no apparent association with e-cigarette use. CONCLUSIONS: Limited low-quality evidence of a non-statistically significant trend toward smoking cessation in adults using nicotine e-cigarettes exists compared with other therapies or placebo. Larger, high-quality studies are needed to inform policy decisions. PMID- 26825456 TI - E-cigarette use among Serbian adults: prevalence and user characteristics. AB - OBJECTIVES: The objective was to report the prevalence and characteristics of electronic cigarette (e-cigarette) users in order to inform an appropriate response to this emerging challenge in tobacco control. METHODS: Data were drawn from a cross-sectional survey conducted in 2014 that used computer-assisted interviewing in a representative sample of 5385 Serbian adults age 18-64 years. RESULTS: Lifetime e-cigarette use and current use was reported by 9.6 and 2 % of adults, respectively. Younger adults had a higher prevalence of both lifetime and current use. Females were more likely to be current e-cigarette users than males. The majority of ever and current e-cigarette users were current or past cigarette smokers, but lifetime use was reported by non-smokers as well. CONCLUSIONS: Electronic cigarettes are popular in Serbia; one in ten adults had tried them at least once. Because females and young adults were more likely to use e cigarettes, a targeted response in these specific groups is needed. A standardised methodology for monitoring e-cigarette use should be established and surveys exploring motives for and attitudes towards e-cigarettes use should be conducted. PMID- 26825457 TI - Aluminum-doped zinc oxide nanoparticles attenuate the TSLP levels via suppressing caspase-1 in activated mast cells. AB - Zinc oxide nanoparticles (ZO-NPs) are used as antimicrobials, anti inflammatories, and to treat cancer. However, although ZO-NPs have excellent efficiency and specificity, their cytotoxicity is higher than that of micron sized zinc oxide. Doping ZO-NPs with aluminum can improve therapeutic efficacy, but the biological effects and mechanisms involved have not been elucidated. Here, we reported the efficacy of aluminum-doped ZO-NP (AZO) on thymic stromal lymphopoietin (TSLP) production and caspase-1 activation in human mast cell line, HMC-1 cells. AZO significantly reduced TSLP levels as well as interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha without inducing cytotoxicity. Furthermore, AZO more effectively reduced TSLP, IL-6, IL-8, and TNF-alpha levels than ZO-NP. The levels of inflammatory cytokine mRNA were also reduced by AZO treatment. AZO blocked production of IL-1beta and activations of caspase-1 and nuclear factor-kappaB by inhibiting IkappaB kinase beta and receptor interacting protein 2. In addition, AZO attenuated phosphorylation of mitogen-activated protein kinases, such as extracellular signal-regulated kinase, c-Jun N-terminal kinases, and p38. These findings provide evidence that AZO improves anti inflammatory properties and offer a safe and effective potential treatment option. PMID- 26825458 TI - Implementing HIV Testing in Substance Use Treatment Programs: A Systematic Review. AB - People who use drugs are at increased risk for HIV acquisition, poor engagement in health care, and late screening for HIV with advanced HIV at diagnosis and increased HIV-related morbidity, mortality, and health care costs. This systematic review evaluates current evidence about the effectiveness and feasibility of implementing HIV testing in U.S. substance use treatment programs. The literature search identified 535 articles. Full text review was limited to articles that explicitly addressed strategies to implement HIV testing in substance use programs: 17 met criteria and were included in the review; nine used quantitative, qualitative, or mixed-method designs to describe or quantify HIV testing rates, acceptance by clients and staff, and cost-effectiveness; eight organization surveys described barriers and facilitators to testing implementation. The evidence supported the effectiveness and feasibility of rapid, routine, and streamlined HIV testing in substance use treatment programs. Primary challenges included organizational support and sustainable funding. PMID- 26825460 TI - Climate and Physiography Predict Mercury Concentrations in Game Fish Species in Quebec Lakes Better than Anthropogenic Disturbances. AB - The fluctuations of mercury levels (Hg) in fish consumed by sport fishers in North-Eastern America depend upon a plethora of interrelated biological and abiological factors. To identify the dominant factors ultimately controlling fish Hg concentrations, we compiled mercury levels (Hg) during the 1976-2010 period in 90 large natural lakes in Quebec (Canada) for two major game species: northern pike (Esox lucius) and walleye (Sander vitreus). Our statistical analysis included 28 geographic information system variables and 15 climatic variables, including sulfate deposition. Higher winter temperatures explained 36% of the variability in higher walleye growth rates, in turn accounting for 54% of the variability in lower Hg concentrations. For northern pike, the dominance of a flat topography in the watershed explained 31% of the variability in lower Hg concentrations. Higher mean annual temperatures explained 27% of the variability in higher pike Hg concentrations. Pelagic versus littoral preferred habitats for walleye and pike respectively could explain the contrasted effect of temperature between the two species. Heavy logging could only explain 2% of the increase in walleye Hg concentrations. The influence of mining on fish Hg concentrations appeared to be masked by climatic effects. PMID- 26825459 TI - High Glucose Stimulates Tumorigenesis in Hepatocellular Carcinoma Cells Through AGER-Dependent O-GlcNAcylation of c-Jun. AB - Epidemiologic studies suggest that hepatocellular carcinoma (HCC) has a strong relationship with diabetes. However, the underlying molecular mechanisms still remain unclear. Here, we demonstrated that high glucose (HG), one of the main characteristics of diabetes, was capable of accelerating tumorigenesis in HCC cells. Advanced glycosylation end product-specific receptor (AGER) was identified as a stimulator during this process. Mechanistically, AGER activated a hexosamine biosynthetic pathway, leading to enhanced O-GlcNAcylation of target proteins. Notably, AGER was capable of increasing activity and stability of proto oncoprotein c-Jun via O-GlcNAcylation of this protein at Ser73. Interestingly, c Jun can conversely enhance AGER transcription. Thereby, a positive autoregulatory feedback loop that stimulates diabetic HCC was established. Finally, we found that AG490, an inhibitor of Janus kinase, has the ability to impair AGER expression and its functions in HCC cells. In conclusion, AGER and its functions to stimulate O-GlcNAcylation are important during liver tumorigenesis, when high blood glucose levels are inadequately controlled. PMID- 26825462 TI - Rad61/Wpl1 (Wapl), a cohesin regulator, controls chromosome compaction during meiosis. AB - Meiosis-specific cohesin, required for the linking of the sister chromatids, plays a critical role in various chromosomal events during meiotic prophase I, such as chromosome morphogenesis and dynamics, as well as recombination. Rad61/Wpl1 (Wapl in other organisms) negatively regulates cohesin functions. In this study, we show that meiotic chromosome axes are shortened in the budding yeast rad61/wpl1 mutant, suggesting that Rad61/Wpl1 negatively regulates chromosome axis compaction. Rad61/Wpl1 is required for efficient resolution of telomere clustering during meiosis I, indicating a positive effect of Rad61/Wpl1 on the cohesin function required for telomere dynamics. Additionally, we demonstrate distinct activities of Rad61/Wpl1 during the meiotic recombination, including its effects on the efficient processing of intermediates. Thus, Rad61/Wpl1 both positively and negatively regulates various cohesin-mediated chromosomal processes during meiosis. PMID- 26825463 TI - A structural view of microRNA-target recognition. AB - It is well established that the correct identification of the messenger RNA targeted by a given microRNA (miRNA) is a difficult problem, and that available methods all suffer from low specificity. We hypothesize that the correct identification of the pairing should take into account the effect of the Argonaute protein (AGO), an essential catalyst of the recognition process. Therefore, we developed a strategy named MiREN for building and scoring three dimensional models of the ternary complex formed by AGO, a miRNA and 22 nt of a target mRNA that putatively interacts with it. We show here that MiREN can be used to assess the likelihood that an RNA molecule is the target of a given miRNA and that this approach is more accurate than other existing methods, usually based on sequence or sequence-related features. Our results also suggest that AGO plays a relevant role in the selection of the miRNA targets. Our method can represent an additional step for refining predictions made by faster but less accurate classical methods for the identification of miRNA targets. PMID- 26825461 TI - RBM3 regulates temperature sensitive miR-142-5p and miR-143 (thermomiRs), which target immune genes and control fever. AB - Fever is commonly used to diagnose disease and is consistently associated with increased mortality in critically ill patients. However, the molecular controls of elevated body temperature are poorly understood. We discovered that the expression of RNA-binding motif protein 3 (RBM3), known to respond to cold stress and to modulate microRNA (miRNA) expression, was reduced in 30 patients with fever, and in THP-1-derived macrophages maintained at a fever-like temperature (40 degrees C). Notably, RBM3 expression is reduced during fever whether or not infection is demonstrable. Reduced RBM3 expression resulted in increased expression of RBM3-targeted temperature-sensitive miRNAs, we termed thermomiRs. ThermomiRs such as miR-142-5p and miR-143 in turn target endogenous pyrogens including IL-6, IL6ST, TLR2, PGE2 and TNF to complete a negative feedback mechanism, which may be crucial to prevent pathological hyperthermia. Using normal PBMCs that were exogenously exposed to fever-like temperature (40 degrees C), we further demonstrate the trend by which decreased levels of RBM3 were associated with increased levels of miR-142-5p and miR-143 and vice versa over a 24 h time course. Collectively, our results indicate the existence of a negative feedback loop that regulates fever via reduced RBM3 levels and increased expression of miR-142-5p and miR-143. PMID- 26825465 TI - Editorial: Managing Strategies for Diverse Diseases: Challenges from Bench to Bedside Translation in Successful Drug Discovery and Development. PMID- 26825464 TI - FANCM interacts with PCNA to promote replication traverse of DNA interstrand crosslinks. AB - FANCM is a highly conserved DNA remodeling enzyme that promotes the activation of the Fanconi anemia DNA repair pathway and facilitates replication traverse of DNA interstrand crosslinks. However, how FANCM interacts with the replication machinery to promote traverse remains unclear. Here, we show that FANCM and its archaeal homolog Hef from Thermoplasma acidophilum interact with proliferating cell nuclear antigen (PCNA), an essential co-factor for DNA polymerases in both replication and repair. The interaction is mediated through a conserved PIP-box; and in human FANCM, it is strongly stimulated by replication stress. A FANCM variant carrying a mutation in the PIP-box is defective in promoting replication traverse of interstrand crosslinks and is also inefficient in promoting FANCD2 monoubiquitination, a key step of the Fanconi anemia pathway. Our data reveal a conserved interaction mode between FANCM and PCNA during replication stress, and suggest that this interaction is essential for FANCM to aid replication machines to traverse DNA interstrand crosslinks prior to post-replication repair. PMID- 26825466 TI - Cadherins: The Superfamily Critically Involved in Breast Cancer. AB - Breast cancer, one of the leading causes of mortality and morbidity among females, is regulated in part by diverse classes of adhesion molecules one of which is known as cadherins. Located at adherens junctions, the members of this superfamily are responsible for upholding proper cell-cell adhesion. Cadherins possess diverse structures and functions and any alteration in their structures or functions causes impeding of normal mammary cells development and maintenance, thus leading to breast malignancy. E-, N-, P-, VE-, Proto-, desmosomal and FAT cadherins have been found to regulate breast cancer in positive as well as negative fashion, whereby both Ecadherin (CDH1) and N-cadherin (CDH2) contribute significantly towards transitioning from epithelial state to mesenchymal state (EMT) and enacting the abnormal cells to invade and metastasize nearby and distant tissues. Aberration in gene expression of cadherins can be either due to somatic or epigenetic silencing or via transcriptional factors. Besides other cadherins, E-cadherin which serves as hallmark of EMT is associated with several regulatory factors such as Snail, Slug, Twist, Zeb, KLF4, NFI, TBX2, SIX, b-Myb, COX-2, Arf6, FOXA2, GATA3 and SMAR1, which modulate E-cadherin gene transcription to promote or represses tumor invasion and colonization. Signaling molecules such as Notch, TGF-beta, estrogen receptors, EGF and Wnt initiate numerous signaling cascades via these vital factors of cell programming, controlling expression of E cadherin at transcriptional (mRNA) and protein level. Thus, interactions of cadherins with their roles in tumor suppression and oncogenic transformation can be beneficial in providing valuable insights for breast cancer diagnosis and therapeutics development. PMID- 26825467 TI - The Effects of Passive Smoking on Laryngeal and Tracheal Mucosa in Male Wistar Rats During Growth: An Experimental Study. AB - Cigarettes contain toxic and carcinogenic substances. In this context, cigarette smoking, and similar activities, are associated with numerous pathologies, being considered a risk factor in up to 10% of the total number of deaths in adults. Recent evidence suggests that the exposure of children to smoking in the early days of their development causes many diseases. Using light microscopy, this study aims to analyze the possible histopathological effects of an experimental model of chronic inhalation of cigarette smoke (passive smoking) on the laryngeal and tracheal mucosa of young Wistar rats. A total of 24 young Wistar rats were studied for a period of 120 days. The animals were divided into two groups: passive smoking (n = 16) and control (n = 8). The level of exposure to cigarette smoke was evaluated from the urinary cotinine level. Although no cancerous lesions were identified, histopathological analysis in the laryngeal and tracheal mucosa of all the animals in the experimental group showed that the proportion of moderate and focal inflammation was higher in animals exposed to chronic inhalation of cigarette smoke (P = 0.041). Histopathologic analysis revealed moderate and focal inflammatory lesions in the region of the infraglottic mucosa in exposed animals, although without dysplastic or neoplastic lesions in the laryngeal and tracheal mucosa. PMID- 26825468 TI - Feasibility Testing: Three-dimensional Tumor Mapping in Different Orientations of Automated Breast Ultrasound. AB - A tumor-mapping algorithm was proposed to identify the same regions in different passes of automated breast ultrasound (ABUS). A total of 53 abnormal passes with 41 biopsy-proven tumors and 13 normal passes were collected. After computer-aided tumor detection, a mapping pair was composed of a detected region in one pass and another region in another pass. Location criteria, including the radial position as on a clock, the relative distance and the distance to the nipple, were used to extract mapping pairs with close regions. Quantitative intensity, morphology, texture and location features were then combined in a classifier for further classification. The performance of the classifier achieved a mapping rate of 80.39% (41/51), with an error rate of 5.97% (4/67). The trade-offs between the mapping and error rates were evaluated, and Az = 0.9094 was obtained. The proposed tumor-mapping algorithm was capable of automatically providing location correspondence information that would be helpful in reviews of ABUS examinations. PMID- 26825470 TI - Effects of eicosapentaenoic acid and docosahexaenoic acid on lipoproteins in hypertriglyceridemia. AB - PURPOSE OF REVIEW: The treatment of hypertriglyceridemia (HTG) with omega-3 fatty acid preparations adds a novel therapy to reduce cardiovascular disease. This review examines the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid on lipoproteins and the cardioprotective effects in HTG. RECENT FINDINGS: The evidence that omega-3 fatty acid therapy at prescription strength is effective and safe at lowering triglyceride levels is growing. Although EPA/docosahexaenoic acid formulations did lower triglyceride levels, an increase in low-density lipoproteins was observed and outcome data were mixed. More recent trials have shown that decreased levels of low-density lipoprotein can be achieved with EPA preparations. Although the cardiovascular outcomes data are not fully available, meta-analysis of available data reports protection against vascular disease. SUMMARY: The addition of omega-3 fatty acid treatment should be considered in patients with severe HTG as well as high-risk patients for atherosclerotic disease. Emerging data are supportive, but long-term outcome studies are still underway. PMID- 26825469 TI - Priorities for transgender medical and healthcare research. AB - PURPOSE OF REVIEW: Transgender individuals experience unique health disparities but are the subject of little focused health research. This manuscript reviews current literature on transgender medical and mental health outcomes and proposes research priorities to address knowledge gaps. RECENT FINDINGS: Published research in transgender healthcare consists primarily of case reports, retrospective and cross-sectional studies, involving largely European settings. Challenges to US-based transgender health research include a diverse population where no single center has sufficient patient base to conduct clinical research with statistical rigor. Treatment regimens are heterogeneous and warrant study for best practices. Current research suggests increased mortality and depression in transgender individuals not receiving optimal care, and possibly a modest increase in cardiovascular risk related to hormone therapy. Current evidence does not support concerns for hormone-related malignancy risk. SUMMARY: The priorities for transgender medical outcomes research should be to determine health disparities and comorbid health conditions over the life span, along with the effects of mental health, medical, and surgical interventions on morbidity and mortality. Specific outcomes of interest based on frequency in the literature, potential severity of outcome, and patient-centered interest, include affective disorders, cardiovascular disease, malignancies, fertility, and time dose-related responses of specific interventions. PMID- 26825471 TI - Lipoprotein(a): novel target and emergence of novel therapies to lower cardiovascular disease risk. AB - PURPOSE OF REVIEW: This article summarizes recent observations on the role of lipoprotein(a) [Lp(a)] as a risk factor mediating cardiovascular disease. RECENT FINDINGS: Lp(a) is a highly prevalent cardiovascular risk factor, with levels above 30 mg/dl affecting 20-30% of the global population. Up until now, no specific therapies have been developed to lower Lp(a) levels. Three major levels of evidence support the notion that elevated Lp(a) levels are a causal, independent, genetic risk factor for cardiovascular disease: epidemiologic studies and meta-analyses, genome-wide association studies and Mendelian randomization studies. Recent studies also have noted that individuals with low levels of Lp(a) are associated with a higher risk of incident type 2 diabetes mellitus, and conversely individuals with high levels have a lower risk, but this association does not appear to be causal. Novel therapies to lower Lp(a) include PCSK9 inhibitors and antisense oligonucleotides directly preventing translation of apolipoprotein(a) mRNA. SUMMARY: With this robust and expanding clinical database, a reawakening of interest in Lp(a) as clinical risk factor is taking place. Trials are underway with novel drugs that substantially lower Lp(a) and may reduce its contribution to cardiovascular disease. PMID- 26825473 TI - The missing evidence in favour of restricting emigration. PMID- 26825472 TI - Research priorities for gender nonconforming/transgender youth: gender identity development and biopsychosocial outcomes. AB - PURPOSE OF REVIEW: The review summarizes relevant research focused on prevalence and natural history of gender nonconforming/transgender youth, and outcomes of currently recommended clinical practice guidelines. This review identifies gaps in knowledge, and provides recommendations foci for future research. RECENT FINDINGS: Increasing numbers of gender nonconforming youth are presenting for care. Clinically useful information for predicting individual psychosexual development pathways is lacking. Transgender youth are at high risk for poor medical and psychosocial outcomes. Longitudinal data examining the impact of early social transition and medical interventions are sparse. Existing tools to understand gender identity and quantify gender dysphoria need to be reconfigured to study a more diverse cohort of transgender individuals. Increasingly, biomedical data are beginning to change the trajectory of scientific investigation. SUMMARY: Extensive research is needed to improve understanding of gender dysphoria, and transgender experience, particularly among youth. Recommendations include identification of predictors of persistence of gender dysphoria from childhood into adolescence, and a thorough investigation into the impact of interventions for transgender youth. Finally, examining the social environments of transgender youth is critical for the development of appropriate interventions necessary to improve the lives of transgender people. PMID- 26825474 TI - A new method for making treatment decisions for incapacitated patients: what do patients think about the use of a patient preference predictor? AB - BACKGROUND: Surrogates frequently are unable to predict which treatment their charges would want and also can experience significant distress as a result of making treatment decisions. A new method, the patient preference predictor (PPP), has been proposed as a possible way to supplement the process of shared decision making to address these two concerns. The PPP predicts which treatment the patient would want based on which treatment similar patients want in similar circumstances. The present article describes the results of the first evaluation to assess whether patients support the use of a PPP. METHODS: Self-administered survey of patients at a tertiary care centre. RESULTS: Overall, 1169 respondents completed the survey (response rate=59.8%). In the event that the respondent became unable to make decisions due to a car accident, 78.9% would want the PPP to be incorporated into the process of making treatment decisions for them. In contrast, 15.2% of respondents would not want the PPP to be used for them. Respondents who endorsed the PPP cited the possibility that its use could increase the chances that they receive the treatments they prefer and/or reduce the burdens on their surrogate decision-maker. CONCLUSIONS: The majority of respondents endorsed the possibility of incorporating a PPP into the process of shared decision-making based on its potential to increase surrogates' predictive accuracy and/or reduce surrogate distress. These data provide strong patient support for further research to assess whether, in practice, the use of a PPP can increase the chances that incapacitated patients receive the treatments they prefer and reduce the burden of making decisions on their surrogates. PMID- 26825475 TI - Response to: 'We could be heroes: ethical issues with the pre-recruitment of research participants' by D. Hunter. PMID- 26825476 TI - Is bias in the eye of the beholder? A vignette study to assess recognition of cognitive biases in clinical case workups. AB - BACKGROUND: Many authors have implicated cognitive biases as a primary cause of diagnostic error. If this is so, then physicians already familiar with common cognitive biases should consistently identify biases present in a clinical workup. The aim of this paper is to determine whether physicians agree on the presence or absence of particular biases in a clinical case workup and how case outcome knowledge affects bias identification. METHODS: We conducted a web survey of 37 physicians. Each participant read eight cases and listed which biases were present from a list provided. In half the cases the outcome implied a correct diagnosis; in the other half, it implied an incorrect diagnosis. We compared the number of biases identified when the outcome implied a correct or incorrect primary diagnosis. Additionally, the agreement among participants about presence or absence of specific biases was assessed. RESULTS: When the case outcome implied a correct diagnosis, an average of 1.75 cognitive biases were reported; when incorrect, 3.45 biases (F=71.3, p<0.00001). Individual biases were reported from 73% to 125% more often when an incorrect diagnosis was implied. There was no agreement on presence or absence of individual biases, with kappa ranging from 0.000 to 0.044. INTERPRETATION: Individual physicians are unable to agree on the presence or absence of individual cognitive biases. Their judgements are heavily influenced by hindsight bias; when the outcome implies a diagnostic error, twice as many biases are identified. The results present challenges for current error reduction strategies based on identification of cognitive biases. PMID- 26825477 TI - Development of a Dietary Index to Assess Overall Diet Quality for Chinese School Aged Children: The Chinese Children Dietary Index. AB - BACKGROUND: A composite measure of diet quality is preferable to an index of nutrients, food groups, or health-promoting behaviors in dietary assessment. However, to date, such a tool for Chinese children is lacking. OBJECTIVE: Based on the current Chinese Dietary Guidelines and Dietary Reference Intakes, a dietary index for Chinese school-aged children, the Chinese Children Dietary Index was developed to assess overall diet quality among children in South China. DESIGN: Dietary data were recorded using 24-hour recalls among 1,719 children aged 7 to 15 years between March and June 2013. Inactivity data and sociodemographic information were also collected. The Chinese Children Dietary Index included 16 components, which incorporated nutrients, foods/food groups, and health-promoting behaviors. The range of possible Chinese Children Dietary Index scores was 0 to 160, with a higher score indicating better diet quality. STATISTICAL ANALYSIS PERFORMED: Pearson/Spearman correlation was used to assess relative validity using correlations between total Chinese Children Dietary Index score and age, body mass index (BMI; calculated as kg/m(2)), inactivity, whole grain intake, frequency of fried-foods intake, nutrient adequacy ratios for energy intake and 12 nutrients not included in the Chinese Children Dietary Index, and the mean adequacy ratio. Finally, a stepwise multiple regression analysis was performed to indicate the factors correlated with Chinese Children Dietary Index. RESULTS: Mean Chinese Children Dietary Index score of this sample was 88.1 points (range=34.2 to 137.8), the Chinese Children Dietary Index score of girls was higher than that of boys and decreased with higher age. Children with higher Chinese Children Dietary Index had lower body mass index and spent less time being inactive. Positive associations were observed between Chinese Children Dietary Index and the majority of nutrient adequacy ratios and the mean adequacy ratio. Age, paternal educational level, and family size were correlated with Chinese Children Dietary Index. CONCLUSIONS: The Chinese Children Dietary Index successfully differentiated diets and, therefore, it can be used to rank order overall diet quality among Chinese children. As the results showed, diet quality among Chinese children needs to be improved, especially in adolescents. PMID- 26825478 TI - Nutritional status of HIV-infected patients during the first year HAART in two West African cohorts. AB - OBJECTIVE: To examine the association between nutritional markers at initiation and during follow up in two different cohorts of HIV-infected adults initiating highly active antiretroviral therapy (HAART) in West Africa. METHODS: The ATARAO study was a one year prospective study carried in Mali. It consisted of a sample of consecutive patients initiating HAART in one of four participating centers during that period. Data were collected at time of treatment initiation (baseline) and every 3 months thereafter. The ANRS 1290 study followed Senegalese patients recruited in similar conditions. Bivariate analyses were used to identify nutritional and immunological covariates of malnutrition at baseline. Longitudinal trajectories of body mass index, hemoglobin and albumin, and their associated factors, were evaluated using mixed linear models. RESULTS: In ATARAO, 250 participants were retained for analyses; of which, 36% had a BMI < 18.5 kg/m(2), nearly 60% were anemic and 47.4% hypoalbuminemic at time of treatment initiation. At baseline, low hemoglobin, hypoalbuminemia and low CD4 levels were associated with a BMI < 18.5 kg/m(2). Similarly, low BMI, low albumin and low CD4 counts were linked to anemia; while, hypoalbuminemia was associated with low hemoglobin levels and CD4 counts. In ANRS, out of the 372 participants retained for analyses, 31% had a low BMI and almost 70% were anemic. At baseline, low BMI was associated with low hemoglobin levels and CD4 counts, while anemia was associated with low CD4 counts and female sex. While treatment contributed to early gains in BMI, hemoglobin and albumin in the first 6 months of treatment, initial improvements plateaued or subsided thereafter. Despite HAART, malnutrition persisted in both cohorts after one year, especially in those who were anemic, hypoalbuminemic or had a low BMI at baseline. CONCLUSION: In ATARAO and ANRS, malnutrition was common across all indicators (BMI, hemoglobin, albumin) and persisted despite treatment. Low BMI, anemia and hypoalbuminemia were associated with attrition, and with a deficient nutritional and immunological status at baseline, as well as during treatment. In spite of therapy, malnutrition is associated with negative clinical and treatment outcomes which suggests that HAART may not be sufficient to address co-existing nutritional deficiencies. PMID- 26825479 TI - Reflections of Low-Income, Second-Generation Latinas About Experiences in Depression Therapy. AB - Depression is higher among second-generation Latinas compared with immigrants, but mental health treatment is stigmatized. Therefore, second-generation Latinas were interviewed after completing an eight-session depression treatment program to gain insight on what they found valuable about their therapy experiences. Constructivist grounded theory guided data collection and analysis which showed that women valued treatment more when they recognized their needs were being met, the therapist was a worthy copilot, and the program's structure had flexibility. Four processes were considered important to their work in therapy: understanding feelings about past events, seeing patterns, accepting self, and changing family patterns but still being "family." Post therapy, women valued their enhanced confidence and a "toolbelt" of techniques they gained for self-treatment. These findings have implications for designing future depression treatment programs that are more likely to be desirable and effective for the growing subgroup of underserved second-generation Latinas in the United States. PMID- 26825480 TI - Use of Social Media Among Individuals Who Suffer From Post-Traumatic Stress: A Qualitative Analysis of Narratives. AB - Suffering from post-traumatic stress impacts and restricts the life situation of the individual on several levels, not least regarding social difficulties. Social media on the Internet facilitate new possibilities for interaction and communication. Earlier research has demonstrated that people use social media to seek support and to discuss health-related issues. The current study aimed to describe how individuals suffering from post-traumatic stress use social media to convey authentic narratives of their daily lives, including illness, and further, to analyze the content of this media use. The data comprised YouTube videos, blogs, and forum discussions. Five categories cover the findings: (a) structure of the narrative, (b) narrating the trauma, (c) restrictions in life, (d) strategies in everyday living, and (e) online interaction. We stress that sharing narratives online facilitates a "verbalizing" of the life conditions of the sufferers and can be used as a self-care activity. PMID- 26825481 TI - Trauma-Focused Cognitive Behavior Therapy: Narratives of Children and Adolescents. AB - Repeated retelling of trauma narratives within Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) assists participants to habituate to experiences that have precipitated symptoms of post-traumatic stress. In this study, the narratives produced by children and adolescents, who developed post-traumatic stress disorder following a natural disaster, and who were treated with a manualized TF-CBT intervention, were examined. The first author developed a coding system utilizing three major concepts (coherence, elaboration, and evaluation) to identify changes in the narratives as they were retold at each therapeutic session. Analysis using this coding system identified that the internal logic of the stories was maintained as the detail diminished, and that the level of evaluation increased. Compression emerged as a major pattern, alongside the reduction in participant distress over the course of the treatment. Although requiring replication, these trial concepts, developed by the coding system, have potential analyzing trauma narratives and enhancing clinician observations. PMID- 26825482 TI - Urban-Dwelling Community Members' Views on Biomedical Research Engagement. AB - In this study, we explore community members' overall understanding and experience with biomedical research engagement. We conducted a qualitative analysis to explore a concept that emerged but was not specifically addressed in a pre existing dataset obtained using four focus group sessions with 30 urban-dwelling community members. Transcripts were read in an iterative process, and an emergent content analysis was performed. Five main themes were identified: (a) engaging in research to contribute to personal or greater good, (b) hierarchy of trust, (c) the importance of disclosure and transparency, (d) practical barriers to research engagement, and (e) fear of research procedures. Community members view research engagement as a collaborative process whereby community members and researchers are involved in all stages of the investigation. Focusing on research engagement, and not merely participation, may enhance community knowledge of the research process and advance scientific knowledge. PMID- 26825483 TI - Normative Social Support in Young Adult Cancer Survivors. AB - Following a cancer diagnosis, young adults (YAs; that is, 18-39) often experience altered social relationships with family, friends, romantic partners, and peers. In light of the social struggles YA patients and survivors report due to cancer's biographical disruption, we elicited narratives from 30 YA cancer survivors to examine how their normative perceptions of social support functioned to hinder and assist them in coping with the cancer experience. Through thematic narrative analysis of their individual accounts, YA survivors explained why and how they perceived various support attempts from peers and loved ones to be effective (i.e., being treated "normally"), ineffective (i.e., receiving pity, negative stories, rudeness, excessive self-monitoring, and returns from estrangement), and both effective and ineffective (e.g., instrumental and relational support) in integrating cancer into their biographies. Implications for the advancement of interpersonal communication theory and for the development of age-appropriate communication interventions, educational programs, and informational resources are discussed. PMID- 26825484 TI - CURB-65 Performance Among Admitted and Discharged Emergency Department Patients With Community-acquired Pneumonia. AB - OBJECTIVES: Pneumonia severity tools were primarily developed in cohorts of hospitalized patients, limiting their applicability to the emergency department (ED). We describe current community ED admission practices and examine the accuracy of the CURB-65 to predict 30-day mortality for patients, either discharged or admitted with community-acquired pneumonia (CAP). METHODS: A retrospective, observational study of adult CAP encounters in 14 community EDs within an integrated healthcare system. We calculated CURB-65 scores for all encounters and described the use of hospitalization, stratified by each score (0 5). We then used each score as a cutoff to calculate sensitivity, specificity, positive predictive value, negative predictive value (NPV), positive likelihood ratios, and negative likelihood ratios for predicting 30-day mortality. RESULTS: The sample included 21,183 ED encounters for CAP (7,952 discharged and 13,231 admitted). The C-statistic describing the accuracy of CURB-65 for predicting 30 day mortality in the full sample was 0.761 (95% confidence interval [CI], 0.747 0.774). The C-statistic was 0.864 (95% CI, 0.821-0.906) among patients discharged from the ED compared with 0.689 (95% CI, 0.672-0.705) among patients who were admitted. Among all ED encounters a CURB-65 threshold of >=1 was 92.8% sensitive and 38.0% specific for predicting mortality, with a 99.9% NPV. Among all encounters, 62.5% were admitted, including 36.2% of those at lowest risk (CURB-65 = 0). CONCLUSIONS: CURB-65 had very good accuracy for predicting 30-day mortality among patients discharged from the ED. This severity tool may help ED providers risk stratify patients to assist with disposition decisions and identify unwarranted variation in patient care. PMID- 26825485 TI - Assessing Intraoperative Bleeding Risk in Patients Undergoing Coronary Artery Bypass Grafting with Prior Exposure to Clopidogrel: Single Center Retrospective Analysis. AB - In patients undergoing coronary artery bypass grafting (CABG), intraoperative and postoperative major bleeding requiring blood transfusions and surgical reexploration is associated with increased mortality and morbidity. Our study hypothesized that exposure to clopidogrel is not significantly associated with increased risk for intraoperative bleeding, even when administered less than 5 days before CABG. We also aimed to determine variables associated with intraoperative packed red blood cell (iPRBC) transfusion. Patients of both sexes aged 18 years or older who underwent CABG from July 1, 2011 to December 31, 2012 were included in the analysis. Study population consisted of 2 groups-clopidogrel arm and nonclopidogrel arm. Patients were included in clopidogrel arm if they were exposed to clopidogrel in the past (as one of their home medications or received the medication for first time during the index hospitalization), whereas patients who never received clopidogrel were included in nonclopidogrel arm. We identified a total of 303 adult patients who underwent CABG with a mean age was 64.5 years. Mortality rate in our study was 0.99% (n = 3) with increased mortality in women as compared with men (3.27% vs. 0.41%, P = 04). The mean iPRBC transfused were 1.68 units, with higher units being transfused in women as compared with men (2.23 vs. 1.49 units, respectively, P = 0.03) and no significant difference between clopidogrel and nonclopidogrel arms (1.92 vs. 1.50, respectively, P = 0.18). After multivariate analysis, age [odds ratio (OR) = 1.03, P = 0.01], female sex (OR = 2.61, P = 0.006) and hypertension (OR = 7.10, P = 0.02) predicted increased iPRBC transfusion. Clopidogrel or nonclopidogrel status was not associated with increased iPRBC transfusion (OR = 1.06, P = 0.81). iPRBC transfusion rates were similar in both arms with age, female sex, and hypertension being an independent predictor of iPRBC transfusion. PMID- 26825486 TI - The Ocular Hypotensive Efficacy of Topical Fasudil, a Rho-Associated Protein Kinase Inhibitor, in Patients With End-Stage Glaucoma. AB - To investigate the effects of topical administration of a selective Rho associated kinase (ROCK) inhibitor, fasudil 0.5% and 1.2% in glaucomatous patients. In this interventional case series study, 4 eyes of 4 patients with unilateral end-stage primary open-angle glaucoma and no light perception vision were assigned to receive topical fasudil 0.5% (in 3 eyes) or 1.2% (in 1 eye) ophthalmic solution twice daily for 8 weeks. At weeks 1, 2, 3, 4, and 8, intraocular pressure (IOP) and adverse events were evaluated. Baseline mean IOP was 53.5 +/- 3.4 mm Hg and mean IOP reductions of the last visit were -8.25 +/- 1.2 mm Hg at 2 hours and -8.75 +/- 2.2 mm Hg at 4 hours. Mean IOP reductions were clinically and statistically significant with 0.5% and 1.2% fasudil and peak effects occurred 2-4 hours after application (P = 0.0002). The largest IOP reductions were produced by 1.2% fasudil (up to -12 mm Hg). Conjunctival hyperemia was found in 1 patient with 1.2% fasudil. Topical administration of fasudil in end-stage primary open-angle glaucoma patients, caused reduction in IOP and was well tolerated. ROCK inhibitors could be considered as a candidate for glaucoma therapy in future. PMID- 26825487 TI - Assessment of Impact of Weight Loss on Left and Right Ventricular Functions and Value of Tissue Doppler Echocardiography in Obese Patients. AB - OBJECTIVE: In our study, we aimed to evaluate the effect of weight loss on left and right ventricular functions in obese patients. METHODS: Thirty patients with a BMI greater than 30 kg/m(2) and without any exclusion criteria were included in the study. Left ventricular systolic and diastolic functions were assessed with conventional and tissue Doppler echocardiography (TDE). At the end of 3 months, echocardiographic examination was repeated in patients with weight loss for cardiac function evaluation and it was compared to the baseline echocardiographic parameters. RESULTS: At the end of 3 months of weight loss period, conventional Doppler echocardiography revealed an improvement in diastolic functions with an increase in mitral E-wave, a decrease in mitral A-wave and an increase in E/A ratio. Deceleration time and isovolumetric relaxation time were ascertained shortened and Tei index decreased. TDE showed an increase in left ventricular lateral wall systolic wave (Sm) and E-wave velocity (Em). Mitral septal annular isovolumetric acceleration time (IVA), Sm and Em, were found to be increased, whereas Tei index was ascertained reduced. Right ventricular tissue Doppler examination following weight loss revealed an increase in RV- IVA, RV-Sm, and RV Em, and a decrease in Tei index. CONCLUSION: We disclosed that left ventricular structural changes and diastolic dysfunction occur in obese patients, and by weight loss, these abnormalities may be reversible which we demonstrated both by conventional and TDE. In addition, obesity might impair RV function as well, and we observed an enhancement in right ventricular functions by weight loss. PMID- 26825488 TI - Evolving Mechanisms of Injury and Management of Pediatric Blunt Renal Trauma--20 Years of Experience. AB - OBJECTIVE: To review 20 years of a prospectively maintained trauma database to identify changing trends in mechanisms of renal injury, demographics, and management outcomes. MATERIALS AND METHODS: Following the approval from the institutional review board, a prospectively maintained trauma database was reviewed for renal trauma patient demographics, management, and mechanisms of injury. Data were reviewed first for the entire cohort and then incrementally to identify mechanisms of injury associated with increasing frequency or grade of injury. RESULTS: A total of 228 graded renal injuries were identified from 1993 to 2013. The majority of renal injuries occurred in males (77.2%) >6 years of age (85.1%). Low grade (I-III) injuries were more common (70.6%). The most frequent mechanisms of injury identified were falls, recreational motor vehicle (RMV) accidents, bike accidents, motor vehicle collisions, and sports accidents, in descending order of frequency. RMV-related injuries have become frequent with time despite recommendations against use in the pediatric age population. Surgical intervention was rarely necessary. Over the 20 year study period, 5 nephrectomies (1.4%) were required, whereas 10 endoscopic interventions or percutaneous drainage procedures were needed (2.4%). CONCLUSION: The majority of blunt pediatric renal injuries are low grade and can be managed nonoperatively. Nephrectomy is rarely required but is indicated for hemodynamic instability refractory to resuscitation. Pediatric blunt renal trauma secondary to RMV use is increasing despite recommendations against their use in the pediatric population. PMID- 26825489 TI - Incidence and Management of Uncomplicated Recurrent Urinary Tract Infections in a National Sample of Women in the United States. AB - OBJECTIVE: To determine the incidence and characteristics of women with uncomplicated recurrent urinary tract infections (UTIs) and to explore whether the use of culture-driven treatment affects rates of UTI-related complications and resource utilization. MATERIALS AND METHODS: Using MarketScan claims from 2003 to 2011, we identified UTI-naive women ages 18-64 with incident uncomplicated recurrent UTIs. Recurrent UTIs were defined as 3 UTI visits associated with antibiotics during a 12-month period. Cases were excluded if they had a UTI in the preceding year, or if they had any complicating factors (eg, abnormality of the urinary tract, neurologic condition, pregnancy, diabetes, or currently taking immunosuppression). We next assessed use of urine cultures, imaging, and cystoscopy, and performed propensity score matching with logistic regression to determine whether having a urine culture associated with >50% of UTIs affected rates of complications and downstream resource utilization. RESULTS: We identified 48,283 women with incident-uncomplicated recurrent UTIs, accounting for an overall incidence of 102 per 100,000 women, highest among women ages 18-34 and 55-64. Sixty-one percent of these women had at least 1 urine culture, 6.9% had imaging, and 2.8% had cystoscopy. Having a urine culture >50% of the time was associated with fewer UTI-related hospitalizations and lower rates of intravenous antibiotic use, whereas demonstrating higher rates of UTI related office visits and pyelonephritis. CONCLUSION: The incidence of uncomplicated recurrent UTIs increases with age. Urine culture-directed care is beneficial in reducing high-cost services including UTI-related hospitalizations and intravenous antibiotic use, making urine cultures a valuable component to management of these patients. PMID- 26825490 TI - Surgical Site Infections in Patients With Type 3 Open Fractures: Comparing Antibiotic Prophylaxis With Cefazolin Plus Gentamicin Versus Piperacillin/Tazobactam. AB - OBJECTIVES: The purpose of this study was to compare rates of surgical site infection (SSI) in patients with type 3 open fractures who had received cefazolin plus gentamicin versus piperacillin/tazobactam for antibiotic prophylaxis. DESIGN: Retrospective cohort study. SETTING: Level 1 trauma center. PATIENTS: Seven hundred sixty-six patients admitted between January 1, 2004, and December 31, 2012, with open fractures were identified using the National Trauma Data Bank by searching International Classification of Diseases, Ninth Revision (ICD-9) codes. Electronic medical record review revealed 134 patients with type 3 open fractures, of which 72 were included in the final analysis. INTERVENTION: Administration of cefazolin plus gentamicin or piperacillin/tazobactam for type 3 open fracture antibiotic prophylaxis. MAIN OUTCOME MEASUREMENTS: SSI, nonunion, death, and rehospitalization rates at 1 year. RESULTS: Surgical site infection at 1 year occurred in 12 of 37 patients (32.4%) in the cefazolin plus gentamicin group and 11 of 35 patients (31.4%) in the piperacillin/tazobactam group (P = 1.000). Nonunion, death, and rehospitalization rates at 1 year were similar between the 2 groups. Although there was no statistically significant difference in SSI at 30 days between groups, the rate was higher in the cefazolin plus gentamicin group (21.6% vs. 11.4%; P = 0.246). CONCLUSIONS: At our institution, use of piperacillin/tazobactam as compared with cefazolin plus gentamicin for antibiotic prophylaxis in patients with type 3 open fractures showed similar rates of SSI, nonunion, mortality, and rehospitalization at 1 year after injury. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 26825491 TI - Intramedullary Nailing of Tibial Shaft Fractures: Size Matters. AB - OBJECTIVES: To determine optimal ratio of intramedullary nail diameter to tibial canal diameter that leads to reliable and timely healing in tibial shaft fractures. DESIGN: Retrospective case series. SETTING: Level I trauma center. PATIENTS: One hundred thirty-three fractures in 132 patients with tibial shaft fractures that underwent intramedullary nailing as definitive fixation were identified between June 2004 and July 2012 at our level I trauma center. Of these, 78 had serial radiographs out to 12 months that could be analyzed for radiographic healing with an average age of 37 years old (range 16-86 years). There were 52 males and 26 females. INTERVENTION: All patients underwent intramedullary nailing of the tibia with documentation of both the diameter of the nail and radiographic canal width at the isthmus to determine the nail to canal ratio. MAIN OUTCOME MEASURES: Patients were followed with serial radiographs for at least 12 months to determine time to healing as a function of nail to canal ratio. The senior author assessed healing at 3, 6, 9, and 12 months using RUST criteria. RESULTS: Patients with an intramedullary nail to canal diameter ratio of less than 0.8 or greater than 0.99 were 4.4 times more likely not to heal than patients with a ratio of between 0.8 and 0.99. CONCLUSION: The ideal intramedullary nail to tibial canal diameter ratio to optimize tibial shaft fracture healing is between 0.8 and 0.99. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 26825492 TI - Prospective Assessment of the Oncogenic Risk to Patients From Fluoroscopy During Trauma Surgery. AB - OBJECTIVE: Concern about radiation exposure during surgery has focused on surgeon exposure. However, the patient receives exposure that is more direct and, in surgery about the pelvis and hip, internal pelvic nonskeletal organs often cannot be shielded without obscuring the region of surgical interest. The purpose of this study was to prospectively evaluate patients' radiation exposure during fracture surgery of the acetabulum, pelvic ring, and femur to calculate future cancer incidence (CI). DESIGN: Prospective descriptive cohort. SETTING: Level-1 trauma center. PATIENTS/PARTICIPANTS: One hundred eight patients with acetabulum, pelvic, or femur fractures requiring operative repair were prospectively enrolled. INTERVENTION: Dosimeters were placed in locations determined for each surgery type by a medical physicist. MAIN OUTCOME MEASUREMENTS: Demographics, operative records, and average x-ray emission energy were recorded. Effective dose, specific organ doses, and lifetime CI for a 30-year-old patient were calculated. RESULTS: Diagnoses included 27 acetabular fractures, 30 intertrochanteric femur fractures, 26 femoral shafts, and 25 pelvic ring injuries. Patients with pelvic ring injuries received the highest effective dose at 0.91 +/- 0.74 mSv. The average lifetime increase in CI, for any cancer type, after pelvic ring fixation is 0.0097% for females and 0.0062% for males. The greatest mean single-organ dose to the ovaries (3.82 +/- 3.34 mGy) occurred during pelvic ring surgery, correlating to an increased ovarian cancer risk of 0.0013%. The greatest mean single-organ dose to the prostate (6.81 +/- 5.91 mSv) also occurred during pelvic surgery, correlating to increased prostate cancer risk of 0.0024%. CONCLUSIONS: Fracture surgery to the pelvis and femur is exceptionally fluoroscopy-dependent; however, the radiation exposure incurred represents a relatively small increased risk of future cancer development in patients. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 26825493 TI - Invited commentary related to: Does the OTA Open Fracture Classification Predict the Need for Limb Amputation? A Retrospective Observational Cohort Study on 512 Patients. PMID- 26825494 TI - Hemostatic/fibrinolytic markers and cardiovascular risk factors in schoolchildren. PMID- 26825496 TI - Assessment of animal African trypanosomiasis (AAT) vulnerability in cattle-owning communities of sub-Saharan Africa. AB - BACKGROUND: Animal African trypanosomiasis (AAT) is one of the biggest constraints to livestock production and a threat to food security in sub-Saharan Africa. In order to optimise the allocation of resources for AAT control, decision makers need to target geographic areas where control programmes are most likely to be successful and sustainable and select control methods that will maximise the benefits obtained from resources invested. METHODS: The overall approach to classifying cattle-owning communities in terms of AAT vulnerability was based on the selection of key variables collected through field surveys in five sub-Saharan Africa countries followed by a formal Multiple Correspondence Analysis (MCA) to identify factors explaining the variations between areas. To categorise the communities in terms of AAT vulnerability profiles, Hierarchical Cluster Analysis (HCA) was performed. RESULTS: Three clusters of community vulnerability profiles were identified based on farmers' beliefs with respect to trypanosomiasis control within the five countries studied. Cluster 1 communities, mainly identified in Cameroon, reported constant AAT burden, had large trypanosensitive (average herd size = 57) communal grazing cattle herds. Livestock (cattle and small ruminants) were reportedly the primary source of income in the majority of these cattle-owning households (87.0%). Cluster 2 communities identified mainly in Burkina Faso and Zambia, with some Ethiopian communities had moderate herd sizes (average = 16) and some trypanotolerant breeds (31.7%) practicing communal grazing. In these communities there were some concerns regarding the development of trypanocide resistance. Crops were the primary income source while communities in this cluster incurred some financial losses due to diminished draft power. The third cluster contained mainly Ugandan and Ethiopian communities which were mixed farmers with smaller herd sizes (average = 8). The costs spent diagnosing and treating AAT were moderate here. CONCLUSIONS: Understanding how cattle-owners are affected by AAT and their efforts to manage the disease is critical to the design of suitable locally adapted control programmes. It is expected that the results could inform priority setting and the development of tailored recommendations for AAT control strategies. PMID- 26825497 TI - Goals and Priorities, Challenges and Solutions. PMID- 26825498 TI - Behavioral Health in the Spotlight. PMID- 26825495 TI - Characterising resting-state functional connectivity in a large sample of adults with ADHD. AB - Attention-deficit/hyperactivity disorder (ADHD) is a common childhood psychiatric disorder that often persists into adulthood. While several studies have identified altered functional connectivity in brain networks during rest in children with ADHD, few studies have been performed on adults with ADHD. Existing studies have generally investigated small samples. We therefore investigated aberrant functional connectivity in a large sample of adult patients with childhood-onset ADHD, using a data-driven, whole-brain approach. Adults with a clinical ADHD diagnosis (N=99) and healthy, adult comparison subjects (N=113) underwent a 9-minute resting-state fMRI session in a 1.5T MRI scanner. After elaborate preprocessing including a thorough head-motion correction procedure, group independent component analysis (ICA) was applied from which we identified six networks of interest: cerebellum, executive control, left and right frontoparietal and two default-mode networks. Participant-level network maps were obtained using dual-regression and tested for differences between patients with ADHD and controls using permutation testing. Patients showed significantly stronger connectivity in the anterior cingulate gyrus of the executive control network. Trends were also observed for stronger connectivity in the cerebellum network in ADHD patients compared to controls. However, there was considerable overlap in connectivity values between patients and controls, leading to relatively low effect sizes despite the large sample size. These effect sizes were slightly larger when testing for correlations between hyperactivity/impulsivity symptoms and connectivity strength in the executive control and cerebellum networks. This study provides important insights for studies on the neurobiology of adult ADHD; it shows that resting-state functional connectivity differences between adult patients and controls exist, but have smaller effect sizes than existing literature suggested. PMID- 26825499 TI - Potentially Dangerous Patients: A Review of the Duty to Warn. PMID- 26825500 TI - Mitigating Nursing Biases in Management of Intoxicated and Suicidal Patients. PMID- 26825501 TI - Response. PMID- 26825502 TI - Potentially Dangerous Patients: A Review of the Duty to Warn. PMID- 26825503 TI - Regarding "Meet Me in Computed Tomography Suite: Decreasing Tissue Plasminogen Activator Door-to-Needle Time for Acute Ischemic Stroke Patients". PMID- 26825504 TI - Customer Satisfaction, Taking Care of the Loved Ones in a Time of Crisis. PMID- 26825505 TI - Response. PMID- 26825508 TI - Special Needs Patients. PMID- 26825506 TI - What Every ED Nurse Should Know About Suicide Risk Assessment. PMID- 26825509 TI - Medicating the "Out of Control" Older Adult. PMID- 26825510 TI - Medical Evaluation of the Behavioral Health Emergency Patient. PMID- 26825511 TI - Behavioral Health Emergencies. PMID- 26825512 TI - Protecting Behavioral Health Research Participants in the ED Setting: Issues of Consent. PMID- 26825513 TI - Rural Level IV Trauma Center; More than a Community Hospital. PMID- 26825515 TI - Association of salivary gland hypofunction with diabetes mellitus and drugs among the elderly in Karachi, Pakistan. AB - AIM: Studies from Pakistan on salivary dysfunction are lacking, and the Pakistani elderly population is rapidly growing. Among the most common problems in the elderly that could have a deleterious impact on their quality of life are salivary gland hypofunction (SGH), diabetes mellitus (DM), and the intake of drugs with adverse effects on salivary function. In the present study, we aimed to find the association of SGH with DM and drugs among the elderly in Karachi, Pakistan. METHODS: The inclusion criterion was affirmative answers to a series of standardized questions related to the symptoms of dry mouth. A total of 110 individuals were selected from a convenience sample of 200 people aged between 60 and 70 years. Diabetes, drug use, and SGH in the participants were determined by detailed medical and drug history, clinical examination, and sialometry. RESULTS: Similar to their international counterparts, the majority of the study participants demonstrated objective evidence of SGH. More importantly SGH was found to be statistically significant with respect to DM and medication (P < 0.05). For participants on medication, the minimum and maximum salivary flow rates were found to be 0.09 mL/min and 0.3 ml/min, respectively, whereas the minimum and maximum salivary flow rates in diabetic participants were 0.01 mL/min and 0.09 mL/min, respectively. CONCLUSION: In the present study, the majority of elderly participants whose presenting complaint was oral dryness was found to have objective evidence of SGH, with a statistically-significant association with DM and drugs. PMID- 26825516 TI - A step toward clinically applicable noninvasive coronary wave intensity analysis. PMID- 26825519 TI - Influence of segmented vessel size due to limited imaging resolution on coronary hyperemic flow prediction from arterial crown volume. AB - Computational predictions of the functional stenosis severity from coronary imaging data use an allometric scaling law to derive hyperemic blood flow (Q) from coronary arterial volume (V), Q = alphaV(beta) Reliable estimates of alpha and beta are essential for meaningful flow estimations. We hypothesize that the relation between Q and V depends on imaging resolution. In five canine hearts, fluorescent microspheres were injected into the left anterior descending coronary artery during maximal hyperemia. The coronary arteries of the excised heart were filled with fluorescent cast material, frozen, and processed with an imaging cryomicrotome to yield a three-dimensional representation of the coronary arterial network. The effect of limited image resolution was simulated by assessing scaling law parameters from the virtual arterial network at 11 truncation levels ranging from 50 to 1,000 MUm segment radius. Mapped microsphere locations were used to derive the corresponding relative Q using a reference truncation level of 200 MUm. The scaling law factor alpha did not change with truncation level, despite considerable intersubject variability. In contrast, the scaling law exponent beta decreased from 0.79 to 0.55 with increasing truncation radius and was significantly lower for truncation radii above 500 MUm vs. 50 MUm (P< 0.05). Hyperemic Q was underestimated for vessel truncation above the reference level. In conclusion, flow-crown volume relations confirmed overall power law behavior; however, this relation depends on the terminal vessel radius that can be visualized. The scaling law exponent beta should therefore be adapted to the resolution of the imaging modality. PMID- 26825518 TI - KV7 channels contribute to paracrine, but not metabolic or ischemic, regulation of coronary vascular reactivity in swine. AB - Hydrogen peroxide (H2O2) and voltage-dependent K(+) (KV) channels play key roles in regulating coronary blood flow in response to metabolic, ischemic, and paracrine stimuli. The KV channels responsible have not been identified, but KV7 channels are possible candidates. Existing data regarding KV7 channel function in the coronary circulation (limited to ex vivo assessments) are mixed. Thus we examined the hypothesis that KV7 channels are present in cells of the coronary vascular wall and regulate vasodilation in swine. We performed a variety of molecular, biochemical, and functional (in vivo and ex vivo) studies. Coronary arteries expressed KCNQ genes (quantitative PCR) and KV7.4 protein (Western blot). Immunostaining demonstrated KV7.4 expression in conduit and resistance vessels, perhaps most prominently in the endothelial and adventitial layers. Flupirtine, a KV7 opener, relaxed coronary artery rings, and this was attenuated by linopirdine, a KV7 blocker. Endothelial denudation inhibited the flupirtine induced and linopirdine-sensitive relaxation of coronary artery rings. Moreover, linopirdine diminished bradykinin-induced endothelial-dependent relaxation of coronary artery rings. There was no effect of intracoronary flupirtine or linopirdine on coronary blood flow at the resting heart rate in vivo. Linopirdine had no effect on coronary vasodilation in vivo elicited by ischemia, H2O2, or tachycardia. However, bradykinin increased coronary blood flow in vivo, and this was attenuated by linopirdine. These data indicate that KV7 channels are expressed in some coronary cell type(s) and influence endothelial function. Other physiological functions of coronary vascular KV7 channels remain unclear, but they do appear to contribute to endothelium-dependent responses to paracrine stimuli. PMID- 26825517 TI - Endocannabinoids in cerebrovascular regulation. AB - The cerebral blood flow is tightly regulated by myogenic, endothelial, metabolic, and neural mechanisms under physiological conditions, and a large body of recent evidence indicates that inflammatory pathways have a major influence on the cerebral blood perfusion in certain central nervous system disorders, like hemorrhagic and ischemic stroke, traumatic brain injury, and vascular dementia. All major cell types involved in cerebrovascular control pathways (i.e., smooth muscle, endothelium, neurons, astrocytes, pericytes, microglia, and leukocytes) are capable of synthesizing endocannabinoids and/or express some or several of their target proteins [i.e., the cannabinoid 1 and 2 (CB1 and CB2) receptors and the transient receptor potential vanilloid type 1 ion channel]. Therefore, the endocannabinoid system may importantly modulate the regulation of cerebral circulation under physiological and pathophysiological conditions in a very complex manner. Experimental data accumulated since the late 1990s indicate that the direct effect of cannabinoids on cerebral vessels is vasodilation mediated, at least in part, by CB1 receptors. Cannabinoid-induced cerebrovascular relaxation involves both a direct inhibition of smooth muscle contractility and a release of vasodilator mediator(s) from the endothelium. However, under stress conditions (e.g., in conscious restrained animals or during hypoxia and hypercapnia), cannabinoid receptor activation was shown to induce a reduction of the cerebral blood flow, probably via inhibition of the electrical and/or metabolic activity of neurons. Finally, in certain cerebrovascular pathologies (e.g., subarachnoid hemorrhage, as well as traumatic and ischemic brain injury), activation of CB2 (and probably yet unidentified non-CB1/non-CB2) receptors appear to improve the blood perfusion of the brain via attenuating vascular inflammation. PMID- 26825520 TI - Exercise training improves vascular mitochondrial function. AB - Exercise training is recognized to improve cardiac and skeletal muscle mitochondrial respiratory capacity; however, the impact of chronic exercise on vascular mitochondrial respiratory function is unknown. We hypothesized that exercise training concomitantly increases both vascular mitochondrial respiratory capacity and vascular function. Arteries from both sedentary (SED) and swim trained (EX, 5 wk) mice were compared in terms of mitochondrial respiratory function, mitochondrial content, markers of mitochondrial biogenesis, redox balance, nitric oxide (NO) signaling, and vessel function. Mitochondrial complex I and complex I + II state 3 respiration and the respiratory control ratio (complex I + II state 3 respiration/complex I state 2 respiration) were greater in vessels from EX relative to SED mice, despite similar levels of arterial citrate synthase activity and mitochondrial DNA content. Furthermore, compared with the SED mice, arteries from EX mice displayed elevated transcript levels of peroxisome proliferative activated receptor-gamma coactivator-1alpha and the downstream targets cytochrome c oxidase subunit IV isoform 1,isocitrate dehydrogenase(Idh)2, and Idh3a, increased manganese superoxide dismutase protein expression, increased endothelial NO synthase phosphorylation (Ser(1177)), and suppressed reactive oxygen species generation (all P< 0.05). Although there were no differences in EX and SED mice concerning endothelium-dependent and endothelium-independent vasorelaxation, phenylephrine-induced vasocontraction was blunted in vessels from EX compared with SED mice, and this effect was normalized by NOS inhibition. These training-induced increases in vascular mitochondrial respiratory capacity and evidence of improved redox balance, which may, at least in part, be attributable to elevated NO bioavailability, have the potential to protect against age- and disease-related challenges to arterial function. PMID- 26825521 TI - Polyphasic analysis of an Azoarcus-Leptothrix-dominated bacterial biofilm developed on stainless steel surface in a gasoline-contaminated hypoxic groundwater. AB - Pump and treat systems are widely used for hydrocarbon-contaminated groundwater remediation. Although biofouling (formation of clogging biofilms on pump surfaces) is a common problem in these systems, scarce information is available regarding the phylogenetic and functional complexity of such biofilms. Extensive information about the taxa and species as well as metabolic potential of a bacterial biofilm developed on the stainless steel surface of a pump submerged in a gasoline-contaminated hypoxic groundwater is presented. Results shed light on a complex network of interconnected hydrocarbon-degrading chemoorganotrophic and chemolitotrophic bacteria. It was found that besides the well-known hydrocarbon degrading aerobic/facultative anaerobic biofilm-forming organisms (e.g., Azoarcus, Leptothrix, Acidovorax, Thauera, Pseudomonas, etc.), representatives of Fe(2+)-and Mn(2+)-oxidizing (Thiobacillus, Sideroxydans, Gallionella, Rhodopseudomonas, etc.) as well as of Fe(3+)- and Mn(4+)-respiring (Rhodoferax, Geobacter, Magnetospirillum, Sulfurimonas, etc.) bacteria were present in the biofilm. The predominance of beta-Proteobacteria within the biofilm bacterial community in phylogenetic and functional point of view was revealed. Investigation of meta-cleavage dioxygenase and benzylsuccinate synthase (bssA) genes indicated that within the biofilm, Azoarcus, Leptothrix, Zoogloea, and Thauera species are most probably involved in intrinsic biodegradation of aromatic hydrocarbons. Polyphasic analysis of the biofilm shed light on the fact that subsurface microbial accretions might be reservoirs of novel putatively hydrocarbon-degrading bacterial species. Moreover, clogging biofilms besides their detrimental effects might supplement the efficiency of pump and treat systems. PMID- 26825522 TI - Modulation of 17beta-estradiol induced estrogenic responses in male goldfish (Carassius auratus) by benzo[a]pyrene and ketoconazole. AB - The aquatic environment is challenged with complex mixtures of chemicals that may interact biochemically with each other in non-target aquatic organisms through a combination of actions, resulting in unpredictable mixture toxicity. This study focuses on the interactive effects of chemicals, including benzo(a)pyrene (BaP) and ketoconazole (KCZ), on 17beta-estradiol (E2)-induced estrogenic responses in male goldfish (Carassius auratus). The possible interactions between BaP or KCZ and E2 were investigated on the expression of cytochromeP4501A (CYP1A, biotransformation enzyme) and on its corresponding catalytic activity 7 ethoxyresorufin-O-deethylase (EROD activity), as well as on the expression of CYP19 (steroidogenic enzyme) and E2 bioaccumulation in liver. Exposure to E2 caused a significant increase in estrogenic responses corresponding with the E2 bioaccumulation. When comparing results to the E2 exposure group, co-exposure to BaP resulted in an increase in the cyp1a mRNA expression and its corresponding EROD activity and a marked decrease in the E2 bioaccumulation, but the expression of aromatase was not altered. Conversely, co-treatment with KCZ significantly suppressed the E2-modulated expression of metabolism and synthesis enzymes, which were accompanied by an increase in the E2 bioaccumulation. These data suggest that the modulation of E2-induced estrogenic responses by BaP and KCZ were correlated to the alterations of E2 bioaccumulation in goldfish, leading to a combination of changes in the capacity of biotransformation and steroidogenesis. The complex interactions between chemicals with different modes of actions highlight the need for caution in determining the safety of combined pollution in the aquatic environment. PMID- 26825523 TI - Acute crack cocaine exposure induces genetic damage in multiple organs of rats. AB - Crack cocaine is a very toxic product derived from cocaine. The aim of this study was to evaluate genetic damage in multiple organs of rats following acute exposure to crack cocaine. A total of 20 Wistar rats were distributed into four groups (n = 5), as follows: 0, 4.5, 9, and 18 mg/kg body weight (b.w.) of crack cocaine administered by intraperitoneal route (i.p.). All animals were killed 24 h after intraperitoneal (i.p.) injection. The results showed that crack cocaine increased the number of micronucleated cells in bone marrow cells exposed to 18 mg/kg crack cocaine (p < 0.05). Peripheral blood and liver cells presented genetic damage as depicted by single cell gel (comet) assay at 9 and 18 mg/kg doses (p < 0.05). Immunohistochemistry data revealed significant increase in 8 hydroxy-20-deoxyguanosine (8-OHdG) immunoexpression in hepatocytes of animals exposed to crack cocaine at 9 and 18 mg/kg (p < 0.05) when compared with negative controls. Taken together, our results demonstrate that crack cocaine is able to induce genomic damage in multiple organs of Wistar rats. PMID- 26825524 TI - Phytoremediation with Geosiphon-like symbiosis? PMID- 26825525 TI - Intimate partner violence as seen in post-conflict eastern Uganda: prevalence, risk factors and mental health consequences. AB - BACKGROUND: Conflict and post-conflict communities in sub-Saharan Africa have a high under recognised problem of intimate partner violence (IPV). Part of the reason for this has been the limited data on IPV from conflict affected sub Saharan Africa. This paper reports on the prevalence, risk factors and mental health consequences of IPV victimisation in both gender as seen in post-conflict eastern Uganda. METHODS: A cross-sectional survey was carried out in two districts of eastern Uganda. The primary outcome of IPV victimisation was assessed using a modified Intimate Partner Violence assessment questionnaire of the American Congress of Obstetricians and Gynaecologists. RESULTS: The prevalence of any form of IPV victimisation (physical and/or sexual and/or psychological IPV) in this study was 43.7 % [95 % CI, 40.1-47.4 %], with no statistically significant difference between the two gender. The factors significantly associated with IPV victimisation were: sub-county (representing ecological factors), poverty, use of alcohol, and physical and sexual war torture experiences. The mental health problems associated with IPV victimisation were probable problem alcohol drinking, attempted suicide and probable major depressive disorder. CONCLUSION: In post-conflict eastern Uganda, in both gender, war torture was a risk factor for IPV victimisation and IPV victimisation was associated with mental health problems. PMID- 26825526 TI - Tobacco smoking is associated with DNA methylation of diabetes susceptibility genes. AB - AIMS/HYPOTHESIS: Tobacco smoking, a risk factor for diabetes, is an established modifier of DNA methylation. We hypothesised that tobacco smoking modifies DNA methylation of genes previously identified for diabetes. METHODS: We annotated CpG sites available on the Illumina Human Methylation 450K array to diabetes genes previously identified by genome-wide association studies (GWAS), and investigated them for an association with smoking by comparing current to never smokers. The discovery study consisted of 630 individuals (Bonferroni-corrected p = 1.4 * 10(-5)), and we sought replication in an independent sample of 674 individuals. The replicated sites were tested for association with nearby genetic variants and gene expression and fasting glucose and insulin levels. RESULTS: We annotated 3,620 CpG sites to the genes identified in the GWAS on type 2 diabetes. Comparing current smokers to never smokers, we found 12 differentially methylated CpG sites, of which five replicated: cg23161492 within ANPEP (p = 1.3 * 10(-12)); cg26963277 (p = 1.2 * 10(-9)), cg01744331 (p = 8.0 * 10(-6)) and cg16556677 (p = 1.2 * 10(-5)) within KCNQ1 and cg03450842 (p = 3.1 * 10(-8)) within ZMIZ1. The effect of smoking on DNA methylation at the replicated CpG sites attenuated after smoking cessation. Increased DNA methylation at cg23161492 was associated with decreased gene expression levels of ANPEP (p = 8.9 * 10(-5)). rs231356-T, which was associated with hypomethylation of cg26963277 (KCNQ1), was associated with a higher odds of diabetes (OR 1.06, p = 1.3 * 10(-5)). Additionally, hypomethylation of cg26963277 was associated with lower fasting insulin levels (p = 0.04). CONCLUSIONS/INTERPRETATION: Tobacco smoking is associated with differential DNA methylation of the diabetes risk genes ANPEP, KCNQ1 and ZMIZ1. Our study highlights potential biological mechanisms connecting tobacco smoking to excess risk of type 2 diabetes. PMID- 26825527 TI - Genetic models rule out a major role of beta cell glycogen in the control of glucose homeostasis. AB - AIMS/HYPOTHESIS: Glycogen accumulation occurs in beta cells of diabetic patients and has been proposed to partly mediate glucotoxicity-induced beta cell dysfunction. However, the role of glycogen metabolism in beta cell function and its contribution to diabetes pathophysiology remain poorly understood. We investigated the function of beta cell glycogen by studying glucose homeostasis in mice with (1) defective glycogen synthesis in the pancreas; and (2) excessive glycogen accumulation in beta cells. METHODS: Conditional deletion of the Gys1 gene and overexpression of protein targeting to glycogen (PTG) was accomplished by Cre-lox recombination using pancreas-specific Cre lines. Glucose homeostasis was assessed by determining fasting glycaemia, insulinaemia and glucose tolerance. Beta cell mass was determined by morphometry. Glycogen was detected histologically by periodic acid-Schiff's reagent staining. Isolated islets were used for the determination of glycogen and insulin content, insulin secretion, immunoblots and gene expression assays. RESULTS: Gys1 knockout (Gys1 (KO)) mice did not exhibit differences in glucose tolerance or basal glycaemia and insulinaemia relative to controls. Insulin secretion and gene expression in isolated islets was also indistinguishable between Gys1 (KO) and controls. Conversely, despite effective glycogen overaccumulation in islets, mice with PTG overexpression (PTG(OE)) presented similar glucose tolerance to controls. However, under fasting conditions they exhibited lower glycaemia and higher insulinaemia. Importantly, neither young nor aged PTG(OE) mice showed differences in beta cell mass relative to age-matched controls. Finally, a high-fat diet did not reveal a beta cell-autonomous phenotype in either model. CONCLUSIONS/INTERPRETATION: Glycogen metabolism is not required for the maintenance of beta cell function. Glycogen accumulation in beta cells alone is not sufficient to trigger the dysfunction or loss of these cells, or progression to diabetes. PMID- 26825528 TI - Optical Coherence Tomography Angiography of Combined Hamartoma of the Retina and Retinal Pigment Epithelium. PMID- 26825529 TI - Rare Variants in the Complement Factor H-Related Protein 5 Gene Contribute to Genetic Susceptibility to IgA Nephropathy. AB - A recent genome-wide association study of IgA nephropathy (IgAN) identified 1q32, which contains multiple complement regulatory genes, including the complement factor H (CFH) gene and the complement factor H-related (CFHRs) genes, as an IgAN susceptibility locus. Abnormal complement activation caused by a mutation in CFHR5 was shown to cause CFHR5 nephropathy, which shares many characteristics with IgAN. To explore the genetic effect of variants in CFHR5 on IgAN susceptibility, we recruited 500 patients with IgAN and 576 healthy controls for genetic analysis. We sequenced all exons and their intronic flanking regions as well as the untranslated regions of CFHR5 and compared the frequencies of identified variants using the sequence kernel association test. We identified 32 variants in CFHR5, including 28 rare and four common variants. The distribution of rare variants in CFHR5 in patients with IgAN differed significantly from that in controls (P=0.002). Among the rare variants, in silico programs predicted nine as potential functional variants, which we then assessed in functional assays. Compared with wild-type CFHR5, three recombinant CFHR5 proteins, CFHR5-M (c.508G>A/p.Val170Met), CFHR5-S (c.533A>G/p.Asn178Ser), and CFHR5-D (c.822A>T/p.Glu274Asp), showed significantly higher C3b binding capacity (CFHR5 M: 109.67%+/-3.54%; P=0.02; CFHR5-S: 174.27%+/-9.78%; P<0.001; CFHR5-D: 127.25%+/ 1.75%; P<0.001), whereas another recombinant CFHR5 (c.776T>A/p.Leu259Termination) showed less C3b binding (56.89%+/-0.57%; P<0.001). Our study found that rare variants in CFHR5 may contribute to the genetic susceptibility to IgAN, which suggests that CFHR5 is an IgAN susceptibility gene. PMID- 26825530 TI - Dynamin-Related Protein 1 Deficiency Improves Mitochondrial Fitness and Protects against Progression of Diabetic Nephropathy. AB - Mitochondrial fission has been linked to the pathogenesis of diabetic nephropathy (DN). However, how mitochondrial fission affects progression of DN in vivo is unknown. Here, we report the effect of conditional podocyte-specific deletion of dynamin-related protein 1 (Drp1), an essential component of mitochondrial fission, on the pathogenesis and progression of DN. Inducible podocyte-specific deletion of Drp1 in diabetic mice decreased albuminuria and improved mesangial matrix expansion and podocyte morphology. Ultrastructure analysis revealed a significant increase in fragmented mitochondria in the podocytes of wild-type diabetic mice but a marked improvement in mitochondrial structure in Drp1-null podocytes of diabetic mice. When isolated from diabetic mice and cultured in high glucose, Drp1-null podocytes had more elongated mitochondria and better mitochondrial fitness associated with enhanced oxygen consumption and ATP production than wild-type podocytes. Furthermore, administration of a pharmacologic inhibitor of Drp1, Mdivi1, significantly blunted mitochondrial fission and rescued key pathologic features of DN in mice. Taken together, these results provide novel correlations between mitochondrial morphology and the progression of DN and point to Drp1 as a potential therapeutic target in DN. PMID- 26825531 TI - Renal Handling of Circulating and Renal-Synthesized Hepcidin and Its Protective Effects against Hemoglobin-Mediated Kidney Injury. AB - Urinary hepcidin may have protective effects against AKI. However, renal handling and the potential protective mechanisms of hepcidin are not fully understood. By measuring hepcidin levels in plasma and urine using mass spectrometry and the kidney using immunohistochemistry after intraperitoneal administration of human hepcidin-25 (hhep25) in C57Bl/6N mice, we showed that circulating hepcidin is filtered by the glomerulus and degraded to smaller isoforms detected in urine but not plasma. Moreover, hepcidin colocalized with the endocytic receptor megalin in proximal tubules, and compared with wild-type mice, megalin-deficient mice showed higher urinary excretion of injected hhep25 and no hepcidin staining in proximal tubules that lack megalin. This indicates that hepcidin is reaborbed in the proximal tubules by megalin dependent endocytosis. Administration of hhep25 concomitant with or 4 hours after a single intravenous dose of hemoglobin abolished hemoglobin-induced upregulation of urinary kidney injury markers (NGAL and KIM-1) and renal Interleukin-6 and Ngal mRNA observed 24 hours after administration but did not affect renal ferroportin expression at this point. Notably, coadministration of hhep25 and hemoglobin but not administration of either alone greatly increased renal mRNA expression of hepcidin-encoding Hamp1 and hepcidin staining in distal tubules. These findings suggest a role for locally synthesized hepcidin in renal protection. Our observations did not support a role for ferroportin in hhep25-mediated protection against hemoglobin induced early injury, but other mechanisms of cellular iron handling may be involved. In conclusion, our data suggest that both systemically delivered and locally produced hepcidin protect against hemoglobin-induced AKI. PMID- 26825533 TI - IgA Structure Variations Associate with Immune Stimulations and IgA Mesangial Deposition. AB - IgA1 mesangial deposition is the hallmark of IgA nephropathy and Henoch-Schonlein purpura, the onset of which often follows infections. Deposited IgA has been reported as polymeric, J chain associated, and often, hypogalactosylated but with no information concerning the influence of the IgA repertoire or the link between immune stimuli and IgA structure. We explored these issues in the alpha1KI mouse model, which produces polyclonal human IgA1 prone to mesangial deposition. Compared with mice challenged by a conventional environment, mice in a specific pathogen-free environment had less IgA deposition. However, serum IgA of specific pathogen-free mice showed more galactosylation and much lower polymerization. Notably, wild-type, alpha1KI, and even J chain-deficient mice showed increased polymeric serum IgA on exposure to pathogens. Strict germfree conditions delayed but did not completely prevent deposition; mice housed in these conditions had very low serum IgA levels and produced essentially monomeric IgA. Finally, comparing monoclonal IgA1 that had different variable regions and mesangial deposition patterns indicated that, independently of glycosylation and polymerization, deposition might also depend on IgA carrying specific variable domains. Together with IgA quantities and constant region post-translational modifications, repertoire changes during immune responses might, thus, modulate IgA propensity to deposition. These IgA features are not associated with circulating immune complexes and C3 deposition and are more pertinent to an initial IgA deposition step preceding overt clinical symptoms in patients. PMID- 26825534 TI - A computational model to explore the role of angiogenic impairment on endochondral ossification during fracture healing. AB - While it is well established that an adequate blood supply is critical to successful bone regeneration, it remains poorly understood how progenitor cell fate is affected by the altered conditions present in fractures with disrupted vasculature. In this study, computational models were used to explore how angiogenic impairment impacts oxygen availability within a fracture callus and hence regulates mesenchymal stem cell (MSC) differentiation and bone regeneration. Tissue differentiation was predicted using a previously developed algorithm which assumed that MSC fate is governed by oxygen tension and substrate stiffness. This model was updated based on the hypothesis that cell death, chondrocyte hypertrophy and endochondral ossification are regulated by oxygen availability. To test this, the updated model was used to simulate the time course of normal fracture healing, where it successfully predicted the observed quantity and spatial distribution of bone and cartilage at 10 and 20 days post fracture (dpf). It also predicted the ratio of cartilage which had become hypertrophic at 10 dpf. Following this, three models of fracture healing with increasing levels of angiogenic impairment were developed. Under mild impairment, the model predicted experimentally observed reductions in hypertrophic cartilage at 10 dpf as well as the persistence of cartilage at 20 dpf. Models of more severe impairment predicted apoptosis and the development of fibrous tissue. These results provide insight into how factors specific to an ischemic callus regulate tissue regeneration and provide support for the hypothesis that chondrocyte hypertrophy and endochondral ossification during tissue regeneration are inhibited by low oxygen. PMID- 26825535 TI - Accelerating achievement of the sustainable development goals. PMID- 26825532 TI - Distinct Requirements for Vacuolar Protein Sorting 34 Downstream Effector Phosphatidylinositol 3-Phosphate 5-Kinase in Podocytes Versus Proximal Tubular Cells. AB - The mechanisms by which the glomerular filtration barrier prevents the loss of large macromolecules and simultaneously, maintains the filter remain poorly understood. Recent studies proposed that podocytes have an active role in both the endocytosis of filtered macromolecules and the maintenance of the filtration barrier. Deletion of a key endosomal trafficking regulator, the class 3 phosphatidylinositol (PtdIns) 3-kinase vacuolar protein sorting 34 (Vps34), in podocytes results in aberrant endosomal membrane morphology and podocyte dysfunction. We recently showed that the vacuolation phenotype in cultured Vps34 deficient podocytes is caused by the absence of a substrate for the Vps34 downstream effector PtdIns 3-phosphate 5-kinase (PIKfyve), which phosphorylates Vps34-generated PtdIns(3)P to produce PtdIns (3,5)P2. PIKfyve perturbation and PtdIns(3,5)P2 reduction result in massive membrane vacuolation along the endosomal system, but the cell-specific functions of PIKfyve in vivo remain unclear. We show here that the genetic deletion of PIKfyve in endocytically active proximal tubular cells resulted in the development of large cytoplasmic vacuoles caused by arrested endocytic traffic progression at a late-endosome stage. In contrast, deletion of PIKfyve in glomerular podocytes did not significantly alter the endosomal morphology, even in age 18-month-old mice. However, on culturing, the PIKfyve-deleted podocytes developed massive cytoplasmic vacuoles. In summary, these data suggest that glomerular podocytes and proximal tubules have different requirements for PIKfyve function, likely related to distinct in vivo needs for endocytic flux. PMID- 26825536 TI - Methods and applications of absolute protein quantification in microbial systems. AB - In the last years the scientific community faced an increased need to provide high-quality data on the concentration of single proteins within a cell. Especially against the background of the fast evolving field of systems biology this does not only apply for a few proteins but preferably for the whole proteome of the organism. Therefore there has been a rapid development from pure identification of proteins via characterization of changes between different conditions by relative protein quantification towards determination of absolute protein amounts for hundreds of protein species in a cell. This review aims for discussion of different small-scale and large-scale approaches for absolute protein quantification in bacterial cells to picture biological processes and explore life in deeper detail. The presented advantages and limitations of various methods may provide interested researchers help to appraise available methods, select the most appropriate technique and avoid common pitfalls during determination of protein concentration in a complex sample. PMID- 26825537 TI - Identification of proteins in susceptible and resistant Brassica oleracea responsive to Xanthomonas campestris pv. campestris infection. AB - Cruciferous plants are important edible vegetables widely consumed around the world, including cabbage, cauli-flower and broccoli. The main disease that affects crucifer plants is black rot, caused by Xanthomonas campestris pv. campestris (Xcc). In order to better understand this specific plant-pathogen interaction, proteins responsive to Xcc infection in resistant (Uniao) and susceptible (Kenzan) Brassica oleracea cultivars were investigated by 2-DE followed by mass spectrometry. A total of 47 variable spots were identified and revealed that in the susceptible interaction there is a clear reduction in the abundance of proteins involved in energetic metabolism and defense. It was interesting to observe that in the resistant interaction, these proteins showed an opposite behavior. Based on our results, we conclude that resistance is correlated with the ability of the plant to keep sufficient photosynthesis metabolism activity to provide energy supplies necessary for an active defense. As a follow-up study, qRT-PCR analysis of selected genes was performed and revealed that most genes showed an up-regulation trend from 5 to 15days after inoculation (DAI), showing highest transcript levels at 15DAI. These results revealed the gradual accumulation of transcripts providing a more detailed view of the changes occurring during different stages of the plant-pathogen interaction. BIOLOGICAL SIGNIFICANCE: In this study we have compared cultivars of Brassica oleracea (cabbage), susceptible and resistant to black rot, by using the classical 2-DE approach. We have found that resistance is correlated with the ability of the plant to keep sufficient photosynthesis metabolism activity to provide energy supplies necessary for an active defense. PMID- 26825538 TI - In-depth quantitative analysis and comparison of the human hepatocyte and hepatoma cell line HepG2 proteomes. AB - Hepatocytes play a pivotal role in human homeostasis. They are essential in regulation of glucose and lipid levels in blood and play a central role in metabolism of amino acids, lipids, drugs and xenobiotic-compounds. In addition, hepatocytes produce a major portion of proteins circulating in the blood. Hepatocytes were isolated from liver tissue obtained from surgical resections. Proteins were extracted and processed using filter aided sample preparation protocol and were analyzed by LC-MS/MS using high accuracy mass spectrometry. Proteins were quantified by the 'Total Protein Approach' and 'Proteomic Ruler'. We report a comprehensive proteomic analysis of purified human hepatocytes and the human hepatoma cell line HepG2. The complete dataset comprises 9400 proteins and provides a comprehensive and quantitative depiction of the proteomes of hepatocytes and HepG2 cells at the protein titer and copy number dimensions. We describe basic cell organization and in detail energy metabolism pathways and metabolite transport. We provide quantitative insights into protein synthesis and drug and xenobiotics catabolism. Our data delineate differences between the native human hepatocytes and HepG2 cells by providing for the first time quantitative data at protein concentrations and copy numbers. PMID- 26825539 TI - Southern blight disease of tomato control by 1-aminocyclopropane-1-carboxylate (ACC) deaminase producing Paenibacillus lentimorbus B-30488. AB - Tomato cultivation is highly susceptible for soil born diseases and among them southern blight disease caused by Scelerotium rolfsii is very common. For its management use of chemical fungicides is not very successful as their spores are able to survive for many years in the soil. As an alternative eco-friendly approach to control the disease antagonistic microbes are being characterized.Among them plant growth promoting rhizobacteria Paenibacillus lentimorbus B-30488 (B-30488) with antagonistic properties, multiple PGP attributes stress tolerance and ACC deaminase enzyme activity is characterized to decipher its mode of action against S. rolfsii under in vitro and in vivo conditions. In vitro results obtained from this study clearly demonstrate that B 30488 has ability to show antagonistic properties under different abiotic stresses against S. rolfsii. Similar results were also obtained from in vivo experiments where B-30488 inoculation has efficiently controlled the disease caused by S. rolfsii and improve the plant growth. Deleterious enhanced ethylene level in S. rolfsii infected plants was also ameliorated by inoculation of ACC deaminase producing B-30488. The ACC accumulation, ACO and ACS activities were also modulated in S. rolfsii infected plants. Results from defense enzymes and other biochemical attributes were also support the role of B-30488 inoculation in ameliorating the biotic stress caused by S. rolfsii in tomato plants. These results were further validated by pathogen related gene expression analysis by real time PCR. Overall results from the present study may be concluded that ACC deaminase producing B-30488 has ability to control the southern blight disease caused by S. rolfsii and commercial bioinoculant package may be developed. PMID- 26825540 TI - Probing the Binding Pocket of the Broadly Tuned Human Bitter Taste Receptor TAS2R14 by Chemical Modification of Cognate Agonists. AB - Sensing potentially harmful bitter substances in the oral cavity is achieved by a group of (~) 25 receptors, named TAS2Rs, which are expressed in specialized sensory cells and recognize individual but overlapping sets of bitter compounds. The receptors differ in their tuning breadths ranging from narrowly to broadly tuned receptors. One of the most broadly tuned human bitter taste receptors is the TAS2R14 recognizing an enormous variety of chemically diverse synthetic and natural bitter compounds, including numerous medicinal drugs. This suggests that this receptor possesses a large readily accessible ligand binding pocket. To allow probing the accessibility and size of the ligand binding pocket, we chemically modified cognate agonists and tested receptor responses in functional assays. The addition of large functional groups to agonists was usually possible without abolishing agonistic activity. The newly synthesized agonist derivatives were modeled in the binding site of the receptor, providing comparison to the mother substances and rationalization of the in vitro activities of this series of compounds. PMID- 26825541 TI - Decursin from Angelica gigas suppresses RANKL-induced osteoclast formation and bone loss. AB - Osteoclasts are the only cells capable of breaking down bone matrix, and excessive activation of osteoclasts is responsible for bone-destructive diseases. In this study, we investigated the effects of decursin from extract of Angelica gigas root on receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast formation using mouse bone marrow-derived macrophages (BMMs). Decursin inhibited RANKL-induced osteoclast formation without cytotoxicity. In particular, decursin maintains the characteristics of macrophages by blocking osteoclast differentiation by RANKL. Furthermore, the RANKL-stimulated bone resorption was diminished by decursin. Mechanistically, decursin blocked the RANKL-triggered ERK mitogen-activated protein kinases (MAPK) phosphorylation, which results in suppression of c-Fos and the nuclear factor of activated T cells (NFATc1) expression. In accordance with the in vitro study, decursin reduced lipopolysaccharide (LPS)- or ovariectomy (OVX)-induced bone loss in vivo. Therefore, decursin exerted an inhibitory effect on osteoclast formation and bone loss in vitro and in vivo. Decursin could be useful for the treatment of bone diseases associated with excessive bone resorption. PMID- 26825542 TI - Distinguishing subgroups among MU-opioid receptor agonists using Na(+),K(+) ATPase as an effector mechanism. AB - We evaluated the effects of intracerebroventricular administration of ouabain on the antinociception induced by five MU-opioid receptor agonists in a tail flick test on female CD-1 mice and the effects of these MU-opioid receptor agonists on mice forebrain synaptosomal ouabain-sensitive Na(+),K(+)-ATPase activity. The subcutaneous administration of the MU-opioid receptor agonists tested produced a dose-dependent antinociceptive effect. The antinociception induced by morphine (1 32 mg/kg), levorphanol (0.4-6.4 mg/kg), and buprenorphine (0.02-0.64 mg/kg) was antagonised in a dose-dependent manner by ouabain (0.001-10 ng, i.c.v.), whilst the antinociception produced by fentanyl (0.02-0.16 mg/kg) and methadone (2-10 mg/kg) was not influenced significantly by ouabain (1-100 ng, i.c.v.). Incubation in vitro of forebrain synaptosomes with morphine (10(-9)-10(-4) M), levorphanol (10(-10)-10(-4) M), buprenorphine (10(-10)-10(-5) M), or fentanyl (10(-10)-10(-5) M) stimulated significantly ouabain-sensitive Na(+),K(+)-ATPase activity in a concentration-dependent way. The order of efficacy (using the Emax as a measure of intrinsic efficacy) was: morphine (29.83+/-0.56%)>levorphanol (18.61+/ 1.26%)>buprenorphine (14.91+/-0.74%)>fentanyl (10.10+/-1.73%). On the other hand, methadone (10(-10)-10(-5) M) did not significantly modify the ouabain-sensitive Na(+),K(+)-ATPase activity (Emax=5.11+/-0.92%). These results suggest that Na(+),K(+)-ATPase activity is involved in the antinociceptive effects of morphine, levorphanol and buprenorphine, but not in that produced by fentanyl and methadone. Thus, we can conclude that at least two subgroups can be distinguished among the MU-opioid receptor agonists taking into consideration the role of Na(+),K(+)-ATPase in their antinociceptive effects. PMID- 26825543 TI - Reduced nitric oxide-mediated relaxation and endothelial nitric oxide synthase expression in the tail arteries of streptozotocin-induced diabetic rats. AB - Diabetes is associated with endothelial dysfunction, which is characterized by impaired endothelium-dependent relaxations. The present study aimed to examine the role of nitric oxide (NO), prostacyclin and endothelium-dependent hyperpolarization (EDH), in the relaxation of ventral tail arteries of rats under diabetic conditions. Relaxations of tail arteries of control and diabetic rats were studied in wire myograph. Western blotting and immunostaining were used to determine the presence of proteins. Acetylcholine-induced relaxations were significantly smaller in arteries of diabetic compared to control rats (Rmax; 70.81 +/- 2.48% versus 85.05 +/- 3.15%). Incubation with the combination of non selective cyclooxygenase (COX) inhibitor, indomethacin and potassium channel blockers, TRAM 34 and UCL 1684, demonstrated that NO-mediated relaxation was attenuated significantly in diabetic compared to control rats (Rmax; 48.47 +/- 5.84% versus 68.39 +/- 6.34%). EDH-type (in the presence of indomethacin and NO synthase inhibitor, LNAME) and prostacyclin-mediated (in the presence of LNAME plus TRAM 34 and UCL 1684) relaxations were not significantly reduced in arteries of diabetic compared to control rats [Rmax: (EDH; 17.81 +/- 6.74% versus 34.16 +/ 4.59%) (prostacyclin; 15.85 +/- 3.27% versus 17.23 +/- 3.75%)]. Endothelium independent relaxations to sodium nitroprusside, salbutamol and prostacyclin were comparable in the two types of preparations. Western blotting and immunostaining indicated that diabetes diminished the expression of endothelial NO synthase (eNOS), while increasing those of COX-1 and COX-2. Thus, since acetylcholine induced NO-mediated relaxation was impaired in diabetes because of reduced eNOS protein expression, pharmacological intervention improving NO bioavailability could be useful in the management of diabetic endothelial dysfunction. PMID- 26825544 TI - Antipsychotic-like effects of zolpidem in Wistar rats. AB - Aside from their use in the treatment of anxiety disorders and insomnia, benzodiazepines and other GABAA receptor positive modulators are widely used as add-on treatments in schizophrenic and non-schizophrenic psychoses. However, there is relatively little direct clinical or pre-clinical evidence for antipsychotic effects of GABAergic medications. Previous studies have indicated that zolpidem, a GABAergic drug acting preferentially at alpha1-containing GABAA receptors, may produce catalepsy through interactions with dopaminergic neurotransmission. The aim of the present study was to investigate effects of zolpidem in experimental models of antipsychotic activity and extrapyramidal side effects in Wistar rats. Effects of zolpidem were compared with that of a classic benzodiazepine drug, diazepam and a second-generation antipsychotic medication, risperidone. High doses of risperidone (10.0mg/kg, i.p.) and zolpidem (10.0mg/kg, i.p.), but not diazepam, induced relatively short-lasting cataleptic responses in the bar test. Zolpidem and risperidone, but not diazepam, produced some antipsychotic-like effects at doses, which produced no catalepsy and did not inhibit spontaneous locomotor activity and apomorphine-induced stereotypies. The present results tend to indicate that zolpidem exerts some neuroleptic-like effects at doses, which do not produce motor side effects. Our findings may provide further rationale for the development of new subtype-selective GABAA receptor modulators for the treatment of psychotic symptoms. PMID- 26825545 TI - PPARgamma activation alters fatty acid composition in adipose triglyceride, in addition to proliferation of small adipocytes, in insulin resistant high-fat fed rats. AB - It was reported that adipocyte size is potentially correlated in part to amount of long chain polyunsaturated fatty acids (PUFAs) and insulin resistance because several long chain PUFAs can be ligands of peroxisome proliferator-activated receptors (PPARs). In our previous study, marked reduction of PUFAs was observed in insulin-resistant high-fat fed rats, which may indicate that PUFAs are consumed to improve insulin resistance. Although PPARgamma agonist, well known as an insulin sensitizer, proliferates small adipocytes, the effects of PPARgamma agonist on FA composition in adipose tissue have not been clarified yet. In the present study, we administered pioglitazone, a PPARgamma agonist, to high-fat fed rats, and measured their FA composition of triglyceride fraction in adipose tissue and adipocyte diameters in pioglitazone-treated (PIO) and non-treated (control) rats. Insulin sensitivity was obtained with hyperinsulinemic euglycemic clamp. Average adipocyte diameter in the PIO group were smaller than that in the control one without change in tissue weight. In monounsaturated FAs (MUFAs), 14:1n-5, 16:1n-7, and 18:1n-9 contents in the PIO group were lower than those, respectively, in the control group. In contrast, 22:6n-3, 20:3n-6, 20:4n-6, and 22:4n-6 contents in the PIO group were higher than those, respectively, in the control group. Insulin sensitivity was higher in the PIO group than in the control one. These findings suggest that PPARgamma activation lowered MUFAs whereas suppressed most of C20 or C22 PUFAs reduction, and that the change of fatty acid composition may be relevant with increase in small adipocytes. PMID- 26825546 TI - Effects of combined PPAR-gamma and PPAR-alpha agonist therapy on fructose induced NASH in rats: Modulation of gene expression. AB - Peroxisome proliferator-activated receptors (PPARs) gamma and alpha have been shown to play key roles in maintaining glucose and lipid homeostasis by acting as insulin sensitizers and lipid-lowering agents respectively, which would make them potential candidates for the treatment of non-alcoholic steatohepatitis (NASH) characterized by insulin resistance, hyperglycemia, and hypertriglyceridemia. The effects of pioglitazone, a PPAR-gamma agonist, and fenofibrate, a PPAR-alpha agonist, as monotherapy and in combination on the expressions of key genes linked to the development of NASH were studied in rats with fructose-induced NASH. Fructose-enriched diet was given to rats for 12 weeks. Fenofibrate (100mg/kg), pioglitazone (4 mg/kg) and combined treatment with both in half doses were given. Body weight, liver index, insulin resistance indices, triglycerides, oxidative stress markers, AST/ALT ratio and TNF-alpha were measured. Additionally, hepatic genes expressions of SOCS-3, sterol regulatory element binding protein-1c, fatty acid synthase, malonyl CoA decarboxylase, TGF-beta1, and adipose tissue genes expressions of leptin and adiponectin were investigated. The combination of both drugs, in half doses, improved NASH-related disturbances similar to, or even better than, a full dose of fenofibrate alone possibly due to attenuating effects of pioglitazone on expression of genes responsible for insulin resistance, fatty acid synthesis and fibrosis in addition to correcting the balance between leptin and adiponectin. Histopathology confirmed the ability of this combination to decrease steatosis area and to normalize hepatic tissue structure. In Conclusion, dual activation of PPAR-gamma and PPAR-alpha has remarkable effect in ameliorating NASH by modulation of some hepatic and adipose tissue genes expressions. PMID- 26825547 TI - Cost efficiency of nursing homes: do five-star quality ratings matter? AB - Nursing homes may respond to the pressure to reduce costs by reducing quality of care, so the two are related. This study examines the determinants of nursing home costs and cost efficiency, and investigates how various measures of nursing home care quality influence both of these. It applies a one-step stochastic frontier approach to a large panel of California nursing homes surveyed between 2009 and 2013. Quality is measured by three different ratings available on the Nursing Home Compare website: rating on quality measures, rating on the health inspection, and rating on staffing levels. Results show that the rating on quality measures, an outcome-based measure of quality, is inversely related to costs but unrelated to mean cost efficiency. In other words, a better rating on quality measures is associated with lower nursing home costs. The health inspection rating is not associated with either costs or mean cost efficiency. The rating for staffing levels, a structural measure of quality, is negatively associated with cost efficiency. These findings reveal that different measures of quality have different relationships with costs and cost efficiency. The findings suggest that better quality outcomes in nursing homes may be achievable with fewer resources and/or improved care procedures, which in turn should reduce nursing home costs. PMID- 26825548 TI - National trends of acute kidney injury requiring dialysis in decompensated cirrhosis hospitalizations in the United States. AB - BACKGROUND AND AIMS: Cirrhosis affects 5.5 million patients with estimated costs of US$4 billion. Previous studies about dialysis requiring acute kidney injury (AKI-D) in decompensated cirrhosis (DC) are from a single center/year. We aimed to describe national trends of incidence and impact of AKI-D in DC hospitalizations. METHODS: We extracted our cohort from the Nationwide Inpatient Sample (NIS) from 2006-2012. We identified hospitalizations with DC and AKI-D by validated ICD9 codes. We analyzed temporal changes in DC hospitalizations complicated by AKI-D and utilized multivariable logistic regression models to estimate AKI-D impact on hospital mortality. RESULTS: We identified a total of 3,655,700 adult DC hospitalizations from 2006 to 2012 of which 78,015 (2.1 %) had AKI-D. The proportion with AKI-D increased from 1.5 % in 2006 to 2.23 % in 2012; it was stable between 2009 and 2012 despite an increase in absolute numbers from 6773 to 13,930. The overall hospital mortality was significantly higher in hospitalizations with AKI-D versus those without (40.87 vs. 6.96 %; p < 0.001). In an adjusted multivariable analysis, adjusted odds ratio for mortality was 2.17 (95 % CI 2.06-2.28; p < 0.01) with AKI-D, which was stable from 2006 to 2012. Changes in demographics and increases in acute/chronic comorbidities and procedures explained temporal changes in AKI-D. CONCLUSIONS: Proportion of DC hospitalizations with AKI-D increased from 2006 to 2009, and although this was stable from 2009 to 2012, there was an increase in absolute cases. These results elucidate the burden of AKI-D on DC hospitalizations and excess associated mortality, as well as highlight the importance of prevention, early diagnosis and testing of novel interventions in this vulnerable population. PMID- 26825549 TI - Regulation of tyrosine hydroxylase is preserved across different homo- and heterodimeric 14-3-3 proteins. AB - Tyrosine hydroxylase (TH) is regulated by members of the 14-3-3 protein family. However, knowledge about the variation between 14-3-3 proteins in their regulation of TH is still limited. We examined the binding, effects on activation and dephosphorylation kinetics of tyrosine hydroxylase (TH) by abundant midbrain 14-3-3 proteins (beta, eta, zeta, gamma and epsilon) of different dimer composition. All 14-3-3 homodimers and their respective 14-3-3epsilon heterodimers bound with similar high affinity (K d values of 1.4-3.8 nM) to serine19 phosphorylated human TH (TH-pS19). We similarly observed a consistent activation of bovine (3.3- to 4.4-fold) and human TH-pS19 (1.3-1.6 fold) across all the different 14-3-3 dimer species, with homodimeric 14-3-3gamma being the strongest activator. Both hetero- and homodimers of 14-3-3 strongly inhibited dephosphorylation of TH-pS19, and we speculate if this is an important homeostatic mechanism of 14-3-3 target-protein regulation in vivo. We conclude that TH is a robust interaction partner of different 14-3-3 dimer types with moderate variability between the 14-3-3 dimers on their regulation of TH. PMID- 26825551 TI - Adult case of staphylococcal scalded skin syndrome differentiated from toxic epidermal necrolysis with the aid of dermoscopy. PMID- 26825550 TI - Flooding of the root system in soybean: biochemical and molecular aspects of N metabolism in the nodule during stress and recovery. AB - Nitrogen fixation of the nodule of soybean is highly sensitive to oxygen deficiency such as provoked by waterlogging of the root system. This study aimed to evaluate the effects of flooding on N metabolism in nodules of soybean. Flooding resulted in a marked decrease of asparagine (the most abundant amino acid) and a concomitant accumulation of gamma-aminobutyric acid (GABA). Flooding also resulted in a strong reduction of the incorporation of (15)N2 in amino acids. Nodule amino acids labelled before flooding rapidly lost (15)N during flooding, except for GABA, which initially increased and declined slowly thereafter. Both nitrogenase activity and the expression of nifH and nifD genes were strongly decreased on flooding. Expression of the asparagine synthetase genes SAS1 and SAS2 was reduced, especially the former. Expression of genes encoding the enzyme glutamic acid decarboxylase (GAD1, GAD4, GAD5) was also strongly suppressed except for GAD2 which increased. Almost all changes observed during flooding were reversible after draining. Possible changes in asparagine and GABA metabolism that may explain the marked fluctuations of these amino acids during flooding are discussed. It is suggested that the accumulation of GABA has a storage role during flooding stress. PMID- 26825552 TI - MicroRNA-10a/10b represses a novel target gene mib1 to regulate angiogenesis. AB - AIMS: MicroRNA-10 (miR-10) was originally shown to regulate angiogenesis by directly modulating the levels of membrane-bound fms-related tyrosine kinase 1 (mflt1) and its soluble splice isoform sflt1 post-transcriptionally in zebrafish. Given that flt1 knockdown incompletely rescues the angiogenic phenotypes in miR 10 morphants, flt1 is unlikely to be the only important target of miR-10 in endothelial cells (ECs). It will be interesting to investigate new mechanism responsible for angiogenic defect induced by miR-10 knockdown. METHODS AND RESULTS: Firstly, we demonstrated that miR-10a and miR-10b (miR-10a/10b) were highly enriched in embryonic zebrafish ECs using deep sequencing, Taqman polymerase chain reaction, and in situ hybridisation. Subsequently, we proved that loss of miR-10a/10b impaired blood vessel outgrowth through regulating tip cell behaviours. Mib1 was identified as a potential direct target of miR-10a/10b through in silicon analysis and in vitro luciferase sensor assay. In vivo reporter assay in zebrafish embryos confirmed the binding of miR-10 with 3'-UTR of zebrafish mib1. Furthermore, inhibition of mib1 and Notch signaling rescued the angiogenic defects in miR-10-deficient zebrafish embryos. In addition, we provided evidences that miR-10 regulates human ECs behaviour through targeting Mib1 as well. CONCLUSION: Taken together, these results indicate that miR-10 regulates the angiogenic behaviour in a Notch-dependent manner by directly targeting mib1. PMID- 26825553 TI - Cardiac hypertrophy is exacerbated in aged mice lacking the osteoprotegerin gene. AB - AIMS: Osteoprotegerin (OPG) may play a role in the progression of cardiac hypertrophy and heart failure. However, its pathophysiological role in changes in cardiac structure and function with ageing remains to be elucidated. METHODS AND RESULTS: We conducted experiments using 2.5- and 12-month-old OPG(-/-) mice and age-matched wild-type (WT) mice and compared the morphology and function of the left ventricle (LV). Both 2.5- and 12-month-old OPG(-/-) mice showed a higher systolic blood pressure and a greater heart weight/body weight ratio than age matched WT mice. Twelve-month-old OPG(-/-) mice had a significantly larger LV chamber and reduced wall thickness compared with age-matched WT mice, and contractile function was decreased. The morphological differences were accompanied by an increase in the number of apoptotic cells and activation of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in the LV of 12 month-old OPG(-/-) mice. Correspondingly, OPG small interfering RNA induced the expressions of TRAIL and cleaved caspase-3 in cultured cardiac myocytes. In addition, these mice revealed a decrease in interstitial fibrosis, activation of matrix metalloproteinase (MMP)-2 and tissue inhibitors of MMP-1 and -2, and inactivation of procollagen alpha1 synthesis. Moreover, intraperitoneal administration of recombinant OPG to either 2.5- or 12-month-old OPG(-/-) mice for 28 days led to partial improvement of LV structure and function without affecting systolic blood pressure. CONCLUSION: These results suggest that OPG plays a role in preserving myocardial structure and function with ageing through a reduction in apoptosis and preservation of the matrix structure. In addition, this appears to be independent of effects on the vasculature. PMID- 26825554 TI - Temporal neutrophil polarization following myocardial infarction. AB - AIMS: Although macrophage phenotypes have been well studied in the myocardial infarction (MI) setting, this study investigated temporal neutrophil polarization and activation mechanisms. METHODS AND RESULTS: Neutrophils isolated from the infarcted left ventricle (LV) of mice showed high expression of proinflammatory markers at Day 1 and anti-inflammatory markers at Days 5 and 7 post-MI, indicating distinct neutrophil phenotypes along the post-MI time continuum. Flow cytometry analysis revealed that although proinflammatory N1 neutrophils were always predominant (>80% of total neutrophils at each time point), the percentage of N2 neutrophils increased post-MI from 2.4 +/- 0.6% at Day 1 to 18.1 +/- 3.0% at Day 7. In vitro, peripheral blood neutrophils were polarized to proinflammatory N1 by lipopolysaccharide and interferon-gamma or anti inflammatory N2 by interleukin-4, indicating high plasticity potential. The in vivo post-MI relevant LV damage-associated molecular patterns (DAMPs) polarized neutrophils to a proinflammatory N1 phenotype by activating toll-like receptor-4. Transforming growth factor-beta1 inhibited proinflammatory production in neutrophils. N1 neutrophils positively correlated with infarct wall thinning at Day 7 post-MI, possibly due to high production of matrix metalloproteinases-12 and -25. CONCLUSION: This study is the first to identify the existence of N1 and N2 neutrophils in the infarct region and reveals that N1 polarization could be mediated by DAMPs. PMID- 26825555 TI - Selective phosphorylation of PKA targets after beta-adrenergic receptor stimulation impairs myofilament function in Mybpc3-targeted HCM mouse model. AB - AIMS: Hypertrophic cardiomyopathy (HCM) has been associated with reduced beta adrenergic receptor (beta-AR) signalling, leading downstream to a low protein kinase A (PKA)-mediated phosphorylation. It remained undefined whether all PKA targets will be affected similarly by diminished beta-AR signalling in HCM. We aimed to investigate the role of beta-AR signalling on regulating myofilament and calcium handling in an HCM mouse model harbouring a gene mutation (G > A transition on the last nucleotide of exon 6) in Mybpc3 encoding cardiac myosin binding protein C. METHODS AND RESULTS: Cardiomyocyte contractile properties and phosphorylation state were measured in left ventricular permeabilized and intact cardiomyocytes isolated from heterozygous (HET) or homozygous (KI) Mybpc3 targeted knock-in mice. Significantly higher myofilament Ca2+sensitivity and passive tension were detected in KI mice, which were normalized after PKA treatment. Loaded intact cardiomyocyte force-sarcomere length relation was impaired in both HET and KI mice, suggesting a reduced length-dependent activation. Unloaded cardiomyocyte function revealed an impaired myofilament contractile response to isoprenaline (ISO) in KI, whereas the calcium-handling response to ISO was maintained. This disparity was explained by an attenuated increase in cardiac troponin I (cTnI) phosphorylation in KI, whereas the increase in phospholamban (PLN) phosphorylation was maintained to wild-type values. CONCLUSION: These data provide evidence that in the KI HCM mouse model, beta-AR stimulation leads to preferential PKA phosphorylation of PLN over cTnI, resulting in an impaired inotropic and lusitropic response. PMID- 26825556 TI - ADHD in college: A qualitative analysis. AB - Attention-deficit/hyperactivity disorder (ADHD) affects many adults and is particularly impairing for emerging adults enrolled in college. Research has shown substantial academic impairment for these individuals. However, research on ADHD impairment has largely been quantitative and focused on children. Therefore, the current study employed Interpretative Phenomenological Analysis to explore the lived experience of college students with ADHD with the following two research questions: (1) What is it like to be a college student with ADHD? and (2) What resources are utilized by college students with ADHD? Thirty-six college students with ADHD were interviewed in focus group settings. Our participants reported a complex and mixed experience living with ADHD in college and varied use of treatments and other accommodations. Specifically, three Constructs emerged in the current study: Consequences of Diagnosis, Impairment, and Treatment Management. Implications for professionals working with these students and future directions for researchers are discussed. PMID- 26825558 TI - HERE'S TO A SWEET SIXTEEN. PMID- 26825557 TI - Magnitude of undernutrition in children aged 2 to 4 years using CIAF and conventional indices in the slums of Mumbai city. AB - Conventional indicators - weight-for-age, height-for-age, weight-for-height and mid-upper arm circumference (MUAC) reflect different facets of the nutritional status. Weight-for-age is the most commonly used indicator. When used individually or in combination, conventional indices fail to depict the overall magnitude of undernutrition in the population. Composite Index of Anthropometric Failure (CIAF) is an alternative classification system which attempts to fill this lacuna. Thus, we undertook this study with the objective to compare the prevalence of undernutrition using CIAF and the conventional indices. We included 634 children aged between 2 to 4 years from anganwadis located in three areas of Mumbai. Weight, height and MUAC measurements were taken. Z scores were computed for weight-for-age (WAZ), height-for-age (HAZ) and weight-for-height (WHZ) using WHO Anthro software. Children were classified as per the conventional indices and CIAF. The prevalence of underweight, stunting and wasting was 35.7%, 33.8% and 18.5% respectively. None of the children had MUAC < 11.5 cm. About 1% of the children were moderately wasted according to MUAC. As per CIAF, 47.8% children were undernourished. According to CIAF, one-third of the undernourished children had single anthropometric failure while half of them had dual failure and 17.1% had multiple failures. When compared with the conventional indices, CIAF could recognize 12.1%, 14.0%, 29.3% and 46.7% more undernourished children than WAZ, HAZ, WHZ and MUAC respectively. In conclusion, CIAF is seen to have many advantages over the conventional indices. CIAF is useful in assessing the overall magnitude of undernutrition and identifying children with multiple anthropometric failures. It also recognizes more undernourished children than all the conventional indices. Therefore, CIAF should be used more widely as a tool for nutritional assessment particularly in developing countries where the burden of undernutrition is high. PMID- 26825559 TI - Gastric Varices: An Overview for the Gastroenterology Nurse. AB - Gastric varices can occur in as many as one-third of patients with portal hypertension. Within the nursing literature, however, articles focus on the management of esophageal varices and portal hypertensive gastrointestinal bleeding with few publications about management of gastric varices. Given the advancement in therapies, it is prudent for gastroenterology nurses to have an understanding of its management and treatment options. This article reviews the pathophysiology, classification, and management of patients with gastric varices and outlines the importance of the nurse's role in the education and ongoing care for this patient group. PMID- 26825560 TI - Meaning of Adherence in Hepatitis C-Infected Military Veterans. AB - Among United States (U.S.) veterans, the prevalence of chronic hepatitis C infection is three times that of the general U.S. population. Treatment success is proportionate to the degree of treatment adherence. There has been little research dedicated to the systematic exploration of issues related to treatment adherence. The purpose of this study was to describe factors that influenced adherence in infected military veterans. Phenomenological research emphasizes a rich description. A convenience sample of 21 veterans was recruited from a clinic in north Texas. One-time in-depth interviews explored reasons for remaining in treatment despite difficult side effects. Analysis included immersion, data transformation, thematic analysis, and summary. Cognitive strategies to stay on medication include making a commitment to treatment, "not ready to leave this world," conserving energy and staying busy, looking forward, and starting over. Veterans utilize previously learned military discipline to stay on medications and follow providers' orders. They are not ready to die and have plans for life after treatment. Patient education should focus on side effect management, rather than on genotypes or viral load. Treatment teams should include substance abuse specialists and gastroenterology providers. Future studies need to develop a measurement tool for adherence during antiviral treatment. PMID- 26825561 TI - Attitudes and Usage of the Food and Drug Administration Adverse Event Reporting System Among Gastroenterology Nurse Practitioners and Physician Assistants. AB - The Food and Drug Administration Adverse Event Reporting System (FAERS) is used for postmarketing pharmacovigilance. Our study sought to assess attitudes and usage of the FAERS among gastroenterology nurse practitioners (NPs) and physician assistants (PAs). A survey was administered at the August 2012 Principles of Gastroenterology for the Nurse Practitioner and Physician Assistant course, held in Chicago, IL. Of the 128 respondents, 123 (96%) reported a specialty in gastroenterology or hepatology and were included in analysis. Eighty-nine participants were NPs and 32 PAs, whereas 2 did not report their profession. Although 119 (98%) agreed or strongly agreed with the statement that accurately reporting adverse drug reactions is an important process to optimize patient safety, the majority of participants (54% NPs and 81% PAs) were unfamiliar with the FAERS. In addition, only 20% of NPs and 9% of PAs reported learning about the FAERS in NP or PA schooling. Our study shows enthusiasm among gastroenterology NPs and PAs for the reporting of adverse drug reactions, coupled with a lack of familiarity with the FAERS. This presents an opportunity for enhanced education about reporting of adverse drug reactions for gastroenterology NPs and PAs. PMID- 26825562 TI - Evidence-Based Selection of Sedation Agents for Patients Undergoing Endoscopic Retrograde Cholangiopancreatography. AB - Sedating patients undergoing advanced endoscopic procedures such as endoscopic retrograde cholangiopancreatography (ERCP) is challenging for the endoscopy team. Considering these challenges and concerns with the use of propofol for deep sedation of older adults and high-risk patients, colleagues of one of the authors (AS) were interested in the identification of techniques for the anesthetic management of subjects undergoing therapeutic ERCP. A search strategy revealed a total of 7 evidence sources. The appraised evidence examined the efficacy and sedation-related effects of anesthesia regimens. Deep sedation with propofol was identified as the most commonly used anesthetic technique for subjects undergoing therapeutic ERCP. The sedation-related unwanted effects of propofol appear to be dose-related and occur more frequently in the high-risk and elderly populations. However, the data were inconclusive in identifying an ideal agent offering superior efficacy with fewer unwanted sedation-related effects. Providers should strongly consider the subject's age, history of coexisting illness, and the pharmacological effects of selected anesthetic agents when choosing an appropriate anesthetic technique. Larger randomized controlled studies are needed to identify risk factors associated with sedation-related complications and to identify alternative options for the anesthetic management of subjects undergoing ERCP. PMID- 26825563 TI - Coping Strategies for Possible Flare-Ups and Their Perceived Effectiveness in Patients With Inflammatory Bowel Disease. AB - The study objective was to investigate the nature and perceived effectiveness of strategies that patients with inflammatory bowel disease (IBD) use in response to worsening symptoms. Questionnaires to investigate the use and perceived effectiveness of 11 types of strategies for coping with possible flare-ups were mailed to 1,641 members of the Crohn's and Colitis Foundation of Japan. The responses were analyzed separately by disease type: ulcerative colitis (UC) and Crohn disease (CD). A total of 400 questionnaires were analyzed from 260 UC and 140 CD patients. The strategies used most by both patient groups were "change contents of meals" and "get more sleep." In addition, "skip some meals" was commonly used by CD patients. The most effective strategies were "use extra topical corticosteroids" (30 of the 56 subjects, 53.6%) among UC patients, and "skip some meals" (70 of the 114 subjects, 61.4%), and "take/add to the elemental diet" (53 of 89 subjects, 59.6%) among CD patients. The coping strategies used most by patients with IBD involved lifestyle modifications. However, the additional use of medications was regarded as the most effective, despite the small number of patients who used this strategy. Additional use of topical medications for UC patients and diet modifications for CD patients should be emphasized in self-management education for patients. PMID- 26825564 TI - The Effect of Abdominal Massage on Constipation and Quality of Life. AB - This study was a randomized controlled trial aimed to find the impact of abdominal massage application on constipation and quality of life among patients. The sample included 30 intervention (abdominal massage) and 30 control subjects. To collect data, the following were utilized: Patient Information Form, Gastrointestinal Symptom Rating Scale, Constipation Severity Instrument, Bristol Scale Stool Form, Patient Assessment of Constipation Quality of Life (PAC-QOL) Scale, and European Quality of Life Instrument (EQ-5D). The data were collected from among patients in the morning and evening on the fourth, fifth, and sixth days postoperatively. No significant findings were discovered between experimental and control groups in terms of individual characteristics and characteristics that might influence constipation (p > .05). It was found that patients who received abdominal massage application defecated more often following their surgery than patients in the control group, which led to a statistically high level of significant difference between the groups (p <= .001). It was also found that the experimental group displayed higher average PAC QOL and EQ-5D scores on discharge. Findings indicated that abdominal massage applied to patients diagnosed with postoperative constipation reduced symptoms of constipation, decreased time intervals between defecation, and increased quality of life. PMID- 26825565 TI - NURSING ASSESSMENT FOR "DO IT YOURSELF" FECAL MICROBIOTA TRANSPLANTATION. PMID- 26825566 TI - MULTIPLE SMALL INTESTINE INTUSSUSCEPTIONS SECONDARY TO THE CERVICAL SPINAL CORD INJURY IN AN ADULT: A RARE PRESENTATION. PMID- 26825567 TI - Letter to the Editor. PMID- 26825568 TI - PHARMACOLOGICAL TREATMENT OF CHILDREN WITH GASTRO-ESOPHAGEAL REFLUX: A SUMMARY. PMID- 26825570 TI - Perception and attitudes towards preventives of malaria infection during pregnancy in Enugu State, Nigeria. AB - BACKGROUND: The objective of this study is to explore and document perceptions and attitude associated with uptake of interventions to prevent malaria in pregnancy infection during pregnancy in Enugu State, Nigeria. METHODS: This is a cross-sectional study in three local government areas in Enugu State to identify the people's perceptions and attitudes towards sleeping under insecticide-treated bednets and uptake of recommended doses of intermittent presumptive treatment during pregnancy. In-depth interview guides were employed to collect data from health workers and mothers who delivered within 6 months preceding the study, while focus group discussion guides were employed in collecting data from grandmothers and fathers of children born within 6 months preceding the study. RESULTS: The people expressed fairly good knowledge of malaria, having lived in the malaria-endemic communities. However, some were ignorant on what should be done to prevent malaria in pregnancy. Those who were aware of the use of insecticide-treated bednets and intermittent presumptive treatment during pregnancy however lamented the attitude of the health workers, who make access to these interventions difficult. CONCLUSIONS: Efforts to prevent malaria in pregnancy should focus on providing health education to pregnant women and their partners, who reinforce what the women are told during antenatal care. The attitude of health workers towards patients, who need these interventions, should be targeted for change. PMID- 26825571 TI - Predicting writing development in dual language instructional contexts: exploring cross-linguistic relationships. AB - This study examined whether decoding and linguistic comprehension abilities, broadly defined by the Simple View of Reading, in grade 1 each uniquely predicted the grade 6 writing performance of English-speaking children (n = 76) who were educated bilingually in both English their first language and French, a second language. Prediction was made from (1) English to English; (2) French to French; and (3) English to French. Results showed that both decoding and linguistic comprehension scores predicted writing accuracy but rarely predicted persuasive writing. Within the linguistic comprehension cluster of tests, Formulating Sentences was a strong consistent within- and between-language predictor of writing accuracy. In practical terms, the present results indicate that early screening for later writing ability using measures of sentence formulation early in students' schooling, in their L1 or L2, can provide greatest predictive power and allow teachers to differentiate instruction in the primary grades. Theoretically, the present results argue that there are correlations between reading-related abilities and writing abilities not only within the same language but also across languages, adding to the growing body of evidence for facilitative cross-linguistic relationships between bilinguals' developing languages. PMID- 26825572 TI - Antiretroviral therapy adherence strategies used by patients of a large HIV clinic in Lesotho. AB - A high degree of adherence to antiretroviral therapy (ART) in patients infected with human immunodeficiency virus (HIV) is necessary for long term treatment effects. This study explores the role of timing of ART intake, the information patients received from health workers, local adherence patterns, barriers to and facilitators of ART among 28 HIV-positive adults at the Senkatana HIV Clinic in Maseru, Lesotho. This qualitative, semi-structured interview study was carried out during February and March of 2011 and responses were analyzed inspired by the Grounded Theory method. Results were then compared and discussed between the authors and the main themes that emerged were categorized. The majority of the respondents reported having missed one or more doses of medicine in the past and it was a widespread belief among patients that they were required to skip the dose of ART if they were "late". The main barriers to adherence were interruptions of daily routines or leaving the house without sufficient medicine. The use of mobile phone alarms, phone clocks and support from family and friends were major facilitators of adherence. None of the patients reported to have been counseled on family support or the use of mobile phones as helpful methods in maintaining or improving adherence to ART. Being on-time with ART was emphasized during counseling by health workers. In conclusion, patients should be advised to take the dose as soon as they remember instead of skipping the dose completely when they are late. Mobile phones and family support could be subjects to focus on during future counseling particularly with the growing numbers of mobile phones in Africa and the current focus on telemedicine. PMID- 26825573 TI - Instant and Lasting Down-Regulation of NR1 Expression in the Hippocampus is Associated Temporally with Antidepressant Activity After Acute Yueju. AB - Accumulating evidence indicated that N-methyl-D-aspartate (NMDA) receptors are involved in the pathophysiology of depression and implicated in therapeutic targets. NMDA antagonists, such as ketamine, displayed fast-onset and long lasting antidepressant activity in preclinical and clinical studies. Previous studies showed that Yueju pill exerts antidepressant effects similar to ketamine. Here, we focused on investigating the association of acute and lasting antidepressant responses of Yueju with time course changes of NMDA receptor subunits NR1, NR2A, and NR2B expressions in the hippocampus, a key region regulating depression response. As a result, Yueju reduced immobility time in the forced swimming test from 30 min to 5 days post a single administration. Yueju acutely decreased NR1 and NR2B protein expression in the hippocampus, with NR2A expression unaltered. NR1 expression remained down-regulated 5 days post Yueju administration, whereas NR2B returned to normal level in 24 h. Yueju and ketamine similarly ameliorated the depression-like symptoms at least for 72 h in learned helplessness test. They both reversed the up-regulated expression of NR1 in the learned helpless mice 1 or 3 days post administration. Different from ketamine, the antidepressant effects of Yueju were not influenced by blockade of amino-3 hydroxy-5-methyl-4-isoxazole propionate receptor. These findings served as preclinical evidence that Yueju may confer acute and long-lasting antidepressant effects by favorably modulating NMDA function in the hippocampus. PMID- 26825574 TI - Low-Dose Homocystine Enhances Proliferation and Migration of Bv2 Microglia Cells. AB - Homocysteine (Hcy) is a non-essential amino acid that is derived from the breakdown of dietary methionine. Hyperhomocysteinemia (HHcy) is an independent risk factor for a variety of chronic diseases, especially neurodegenerative conditions. To better understand the role of HHcy in the pathogenesis of neurodegenerative disorders, we investigated the effect of Hcy on the proliferation and activation of microglia Bv2 cells. Cells were treated with six different Hcy concentrations: 0, 50, 100, 300, 500, and 1000 uM for different time periods (8, 12, 16, 24, and 48 h). The morphology of Bv2 cells was observed, and cell activity and proliferation were detected. Cell migration and secretion of pro-inflammatory cytokines were detected by the scratch wound assay, the transwell assay, and ELISA, respectively. The effect of Hcy on Bv2 proliferation occurred earlier (<24 h, especially 16 h) after treatment with concentrations between 100 and 300 MUM, and there was no cytotoxicity to Bv2 cells. Meanwhile, functional assays suggested that Hcy not only promoted Bv2 secretion of the pro inflammatory cytokines IL-1beta, TNF-alpha, and IL-6, but also enhanced Bv2 migration and invasion, with 100 MUM being the most effective concentration. In summary, Bv2 proliferation and activation can be promoted by short-term treatment with low-dose Hcy. PMID- 26825576 TI - Rosacea: Diagnosis and management. PMID- 26825577 TI - New Findings on the Neurobiology of Dementia and Dementia Risk. PMID- 26825575 TI - Ophthalmic Manifestations and Long-Term Visual Outcomes in Patients with Cobalamin C Deficiency. AB - PURPOSE: To explore the ocular manifestations of cobalamin C (cblC) deficiency, an inborn error of intracellular vitamin B12 metabolism. DESIGN: Retrospective, observational case series. PARTICIPANTS: Twenty-five cblC patients underwent clinical and ophthalmic examination at the National Institutes of Health between August 2004 and September 2012. Patient ages ranged from 2 to 27 years at last ophthalmic visit, and follow-up ranged from 0 to 83 months (median, 37 months; range, 13-83 months) over a total of 69 visits. METHODS: Best-corrected visual acuity, slit-lamp biomicroscopy, dilated fundus examination, wide-field photography, fundus autofluorescence imaging, sedated electroretinography, optical coherence tomography, genetics and metabolite assessment. MAIN OUTCOME MEASURES: Visual acuity and presence and degree of retinal degeneration and optic nerve pallor. RESULTS: Nystagmus (64%), strabismus (52%), macular degeneration (72%), optic nerve pallor (68%), and vascular changes (64%) were present. c.271dupA (p.R91KfsX14) homozygous patients (n = 14) showed early and extensive macular degeneration. Electroretinography showed that scotopic and photopic responses were reduced and delayed, but were preserved remarkably in some patients despite severe degeneration. Optical coherence tomography images through the central macular lesion of a patient with severe retinal degeneration showed extreme thinning, some preservation of retinal lamination, and nearly complete loss of the outer nuclear layer. Despite hyperhomocysteinemia, no patients exhibited lens dislocation. CONCLUSIONS: This longitudinal study reports ocular outcomes in the largest group of patients with cblC deficiency systematically examined at a single center over an extended period. Differences in progression and severity of macular degeneration, optic nerve pallor, and vascular attenuation between homozygous c.271dupA (p.R91KfsX14) patients and compound heterozygotes were noted. The pace and chronicity of ophthalmic manifestations lacked strict correlation to metabolic status as measured during visits. Prenatal or early treatment, or both, may have mitigated ocular disease, leading to better functional acuity, but patients still progressed to severe macular degeneration. The effects of prenatal or early treatment, or both, in siblings; the manifestation of severe disease in infancy; the presence of comorbid developmental abnormalities; and the possible laminar structural defect noted in many patients are findings showing that cblC deficiency displays a developmental as well as a degenerative ocular phenotype. PMID- 26825578 TI - The long noncoding RNA colon cancer-associated transcript-1/miR-490 axis regulates gastric cancer cell migration by targeting hnRNPA1. AB - Colon cancer-associated transcript-1 (CCAT1) is a highly conserved long noncoding RNA that is deregulated in several cancers. However, its role in gastric carcinoma and its post-transcriptional regulation remain poorly understood. In this study, we provide the first evidence that CCAT1 regulates miR-490 in gastric cancer (GC) cells. Interestingly, miR-490 can also repress CCAT1 expression. CCAT1 expression was significantly upregulated, and miR-490 expression was downregulated in GC. The negative correlation between miR-490 and CCAT1 expression was observed in GC tissues. Importantly, CCAT1 contains a putative miR 490-binding site, and deletion of this binding site abolishes their miR-490 responsiveness. Post-transcriptional CCAT1 silencing by miR-490 significantly suppressed GC cell migration. Furthermore, miR-490 directly bound to the hnRNPA1 mRNA 3'-UTR to repress its translation. Inhibition of miR-490 rescued CCAT1 siRNA mediated suppression of cell migration. hnRNPA1 expression was significantly upregulated in GC specimens, and there was a negative correlation between miR-490 and hnRNPA1 expression and also a positive correlation between hnRNAP1 expression level and CCAT1 level. Taken together, we show for the first time that the CCAT1/miR-490/hnRNPA1 axis promotes GC migration, and it may have a possible diagnostic and therapeutic potential in GC. PMID- 26825579 TI - A higher frequency of IL-10-producing B cells in Hepatitis B virus-associated membranous nephropathy. AB - The purpose of this study is to elucidate the potential role of interleukin (IL) 10(+) regulatory B cells and other B cell subsets in the development of hepatitis B virus-associated membranous nephropathy (HBV-MN). A total of 14 patients with new onset HBV-MN, 12 individuals with immune-tolerant HBV infection (HBV-IT), and 12 healthy controls (HC) were examined for the percentages of CD38(+) , CD86(+) , CD27(+) , CD95(+) and IL-10(+) B cells by flow cytometry. Serum IL-10 concentration was examined by enzyme-linked immunosorbent assay (ELISA). The percentages of CD38(+) CD19(+) , CD86(+) CD19(+) , CD38(+) CD86(+) CD19(+) , and CD95(+) CD19(+) B cells were significantly higher in HBV-MN patients than the HBV IT and HC. The percentages of CD5(+) CD19(+) , IL-10(+) CD19(+) B cells and serum IL-10 level in HBV-MN patients were significantly higher than the HC, and lower than the HBV-IT. Percentages of CD38(+) CD19(+) , and CD86(+) CD19(+) B cells were reduced after treatment, while the percentages of CD5(+) CD1d(+) CD19(+) , CD5(+) CD1d(+) IL-10(+) CD19(+) , and IL-10(+) CD19(+) B cells were increased. The 24 h urinary protein concentration was positively correlated with the percentage of CD38(+) CD19(+) , and negatively correlated with the percentage of IL-10(+) CD19(+) B cells and serum IL-10 level. Similarly, the value of eGFR was negatively correlated with the percentage of CD38(+) CD19(+) , and positively correlated with the percentage of IL-10(+) CD19(+) B cells and serum IL-10 level. Serum IL-10 level and the percentage of IL-10(+) CD19(+) were negatively correlated with the percentages of CD38(+) CD19(+) , and CD86(+) CD19(+) B cells. These results suggest that CD86(+) CD19(+) , CD38(+) CD86(+) CD19(+) , CD95(+) CD19(+) , and especially CD38(+) CD19(+) and IL-10(+) CD19(+) cells may participate in the pathogenesis of HBV-MN. PMID- 26825580 TI - A baseline study of coastal water quality in the Lembeh Strait of North Sulawesi, Indonesia, in 2013. AB - The concentrations of nutrients (NO2-N, NO3-N, NH4-N, PO4-P, and SiO3-Si) and their ratios in the Lembeh Strait were estimated in April 2013, off the northeastern coast of Sulawesi in Indonesia. The concentrations of dissolved inorganic nitrogen (DIN) (NO2-N+NO3-N+NH4-N) and PO4-P were low, with a maximum of 0.181 and 0.007 mg/L, respectively. P was found to be the limiting factor controlling phytoplankton growth overall. According to a potential eutrophication assessment model, both the surface water and the water at a depth of 15m were classified as water 1 (poor nutrition). This study provides baseline information including chemical datasets for future pollution monitoring and management programs in this area. PMID- 26825581 TI - Urinary angiotensinogen excretion is associated with blood pressure in obese young adults. AB - Intrarenal RAS has been suggested to be involved in the pathogenesis of hypertension. It was recently reported that urinary angiotensinogen excretion levels are associated with intrarenal RAS. However, few markers predicting intrarenal RAS have been investigated in obese young subjects. The present study evaluated the association between blood pressure and intrarenal RAS activity, inflammation and oxidative stress in obese young adults. Urinary angiotensinogen excretion and urinary monocyte chemotactic protein (MCP)-1, and urinary thiobarbituric acid reaction substance (TBARS) as markers of intrarenal RAS activity, inflammation, and oxidative stress, respectively, were determined from morning urine of 111 young male adults. Participants were divided into two groups based on the body mass index (BMI). Natural log-transformed urinary angiotensinogen excretion level was significantly associated with blood pressure, MCP-1 excretion, and TBARS excretion elevation in the obese group (BMI >=25 kg/m(2)). Multivariable analyses showed that every 1 standard deviation increase in natural-log transformed urinary angiotensinogen and MCP-1 excretion, but not TBARS excretion level was associated with elevated blood pressure in the obese group. These results indicate that urinary angiotensinogen and MCP-1 excretion were associated with blood pressure elevation in this population of obese young adults. It suggested that inappropriate RAS activity and inflammation precedes hypertension in obese young subjects and urinary angiotensinogen could be a screening maker for hypertension in young obese subjects. PMID- 26825583 TI - Shedding light on research participation effects in behaviour change trials: a qualitative study examining research participant experiences. AB - BACKGROUND: The sequence of events in a behaviour change trial involves interactions between research participants and the trial process. Taking part in such a study has the potential to influence the behaviour of the participant, and if it does, this can engender bias in trial outcomes. Since participants' experience has received scant attention, the aim of this study is thus to generate hypotheses about which aspects of the conduct of behaviour change trials might matter most to participants, and thus have potential to alter subsequent behaviours and bias trial outcomes METHODS: Twenty participants were opportunistically screened for a health compromising behaviour (unhealthy diet, lack of exercise, smoking or alcohol consumption) and recruited if eligible. Semi structured face to face interviews were conducted, after going through the usual processes involved in trial recruitment, baseline assessment and randomisation. Participants were given information on the contents of an intervention or control condition in a behaviour change trial, which was not actually implemented. Three months later they returned to reflect on these experiences and whether they had any effect on their behaviour during the intervening period. Data from the latter interview were analysed thematically using a modified grounded theory approach. RESULTS: The early processes of trial participation raised awareness of unhealthy behaviours, although most reported having had only fleeting intentions to change their behaviour as a result of taking part in this study, in the absence of interventions. However, careful examination of the accounts revealed evidence of subtle research participation effects, which varied according to the health behaviour, and its perceived social acceptability. Participants' relationships with the research study were viewed as somewhat important in stimulating thinking about whether and how to make lifestyle changes. CONCLUSION: These participants described no dramatic impacts attributable to taking part in this study. This study demonstrates the likely value of well conducted qualitative studies of subtle research participation effects, which may be particularly important to explore for alcohol. Separating unintended influences in trial participation from the effects of behaviour change interventions being evaluated therein is necessary for valid estimates of intervention effects. PMID- 26825584 TI - Characterization of premorbid functioning during childhood in patients with deficit vs. non-deficit schizophrenia and in their healthy siblings. AB - Impaired premorbid adjustment has been reported in patients with schizophrenia, generally in association with unfavorable aspects of the illness (e.g., poor outcome and severe negative symptoms). Several studies attempted to define the domains of premorbid dysfunction associated with negative symptoms and poor outcome; however, most of them assessed broadly defined negative symptoms. The present study was aimed to characterize premorbid functioning in a group of patients with deficit schizophrenia (DS), characterized by the presence of at least two primary and persistent negative symptoms (PPNS), and one of patients with a diagnosis of schizophrenia who did not meet criteria for DS (NDS). The presence of emotional/behavioral problems during childhood was investigated using the Childhood Behavior Checklist (CBCL) in both patient groups and in their respective healthy siblings. The Premorbid Adjustment Scale (PAS) was also used to assess premorbid functioning during childhood in the two patient groups. PPNS were also treated as a continuous variable and correlated with the indices of premorbid functioning regardless the DS/NDS categorization. DS patients, as compared to NDS, showed higher scores on the CBCL subscale "Withdrawn". Both DS and NDS patients showed, as compared to their healthy siblings, a greater impairment on almost all CBCL subscales. PAS findings revealed that DS patients had poorer premorbid adjustment than NDS. No significant correlation between premorbid functioning and PPNS was observed. These findings support the hypothesis that DS has a different developmental trajectory with respect to NDS, and that premorbid adjustment is one of the essential aspects of its characterization. PMID- 26825586 TI - Identification of dietary patterns by factor analysis and study of the relationship with nutritional status of rural adolescents using factor scores. AB - Study was undertaken to know food and nutrient consumption patterns and their relationship with nutritional status among rural adolescents in Orissa. It was a Community based cross sectional study, conducted at district level in the State of Orissa. Data on 686 adolescent boys and 689 adolescent girls were utilized. Factor analysis was used to find dietary pattern and discriminate analysis and its relationship with undernutrition. The study revealed that among adolescent boys, there existed six patterns among food-groups and three patterns among nutrients explaining 52% and 76% of total variation. Similarly among adolescent girls, seven patterns among food groups and three patterns among nutrients, explaining 67% and 80% of total variation. The discriminate analysis using the factor scores revealed overall 56% of adolescent boys, and 53% of girls were correctly classified. About 46% of boys who were actually thin were predicted as normal, while, 40% who were normal were predicted as thin. Among girls 50% who were actually thin were predicted as normal, while, 36% who were normal were predicted as thin. In conclusions, there exists considerable relationship between dietary patterns and nutritional status among rural adolescents. PMID- 26825585 TI - Mangiferin ameliorates Porphyromonas gingivalis-induced experimental periodontitis by inhibiting phosphorylation of nuclear factor-kappaB and Janus kinase 1-signal transducer and activator of transcription signaling pathways. AB - BACKGROUND AND OBJECTIVE: Mangiferin is a natural polyphenol compound with anti inflammatory properties. However, there have been few reports on the effect of mangiferin on periodontitis. Here, we investigated the anti-inflammatory effects of this compound on experimental periodontitis and the underlying mechanisms. MATERIAL AND METHODS: Mice were inoculated with Porphyromonas gingivalis to induce periodontitis, and treated with mangiferin orally (50 mg/kg bodyweight, once a day) for 8 wk. Then, the alveolar bone loss was examined using a scanning electronic microscope. Expression of tumor necrosis factor-alpha (TNF-alpha) and the phosphorylation levels of nuclear factor-kappaB (NF-kappaB) and Janus kinase 1-signal transducer and activator of adhesion (JAK1-STAT) pathways in the gingival epithelium were detected using western blot analysis and immunohistochemical staining. RESULTS: The results showed that mice with periodontitis exhibited greater alveolar bone loss, stronger expression of TNF alpha and higher phosphorylation levels of NF-kappaB and JAK1-STAT1/3 pathways in gingival epithelia, compared with control mice with no periodontitis. Moreover, treatment with mangiferin could significantly inhibit alveolar bone loss, TNF alpha production and phosphorylation of NF-kappaB and JAK1-STAT1/3 pathways in gingival epithelia. CONCLUSION: Mangiferin has anti-inflammatory effects on periodontitis, which is associated with its ability to down-regulate the phosphorylation of NF-kappaB and JAK1-STAT1/3 pathways in gingival epithelia. PMID- 26825587 TI - Care of Older Adults: Role of Primary Care Physicians in the Treatment of Cataracts and Macular Degeneration. AB - This article aims to facilitate optimal management of cataracts and age-related macular degeneration (AMD) by providing information on indications, risk factors, referral guidelines, and treatments and to describe techniques to maximize quality of life (QOL) for people with irreversible vision loss. A review of PubMed and other online databases was performed for peer-reviewed English language articles from 1980 through August 2012 on visual impairment in elderly adults. Search terms included vision loss, visual impairment, blind, low vision, QOL combined with age-related, elderly, and aging. Articles were selected that discussed vision loss in elderly adults, effects of vision impairment on QOL, and care strategies to manage vision loss in older adults. The ability of primary care physicians (PCPs) to identify early signs of cataracts and AMD in individuals at risk of vision loss is critical to early diagnosis and management of these common age-related eye diseases. PCPs can help preserve vision by issuing aptly timed referrals and encouraging behavioral modifications that reduce risk factors. With knowledge of referral guidelines for soliciting low vision rehabilitation services, visual aids, and community support resources, PCPs can considerably increase the QOL of individuals with uncorrectable vision loss. By offering appropriately timed referrals, promoting behavioral modifications, and allocating low-vision care resources, PCPs may play a critical role in preserving visual health and enhancing the QOL for the elderly population. PMID- 26825588 TI - Evidence based management of polyps of the gall bladder: A systematic review of the risk factors of malignancy. AB - BACKGROUND: There are no evidence-based guidelines to dictate when Gallbladder Polyps (GBPs) of varying sizes should be resected. AIM: To identify factors that accurately predict malignant disease in GBP; to provide an evidence-based algorithm for management. METHODS: A systematic review following PRISMA guidelines was performed using terms "gallbladder polyps" AND "polypoid lesion of gallbladder", from January 1993 and September 2013. Inclusion criteria required histopathological report or follow-up of 2 years. RTI-IB tool was used for quality analysis. Correlation with GBP size and malignant potential was analysed using Euclidean distance; a logistics mixed effects model was used for assessing independent risk factors for malignancy. RESULTS: Fifty-three articles were included in review. Data from 21 studies was pooled for analysis. Optimum size cut-off for resection of GBPs was 10 mm. Probability of malignancy is approximately zero at size <4.15 mm. Patient age >50 years, sessile and single polyps were independent risk factors for malignancy. For polyps sized 4 mm-10 mm, a risk assessment model was formulated. CONCLUSIONS: This review and analysis has provided an evidence-based algorithm for the management of GBPs. Longitudinal studies are needed to better understand the behaviour of polyps <10 mm, that are not at a high risk of malignancy, but may change over time. PMID- 26825589 TI - Prebiotics and synbiotics: dietary strategies for improving gut health. AB - PURPOSE OF REVIEW: A wide range of dietary carbohydrates, including prebiotic food ingredients, fermentable fibers, and milk oligosaccharides, are able to produce significant changes in the intestinal microbiota. These shifts in the microbial community are often characterized by increased levels of bifidobacteria and lactobacilli. More recent studies have revealed that species of Faecalibacterium, Akkermansia, and other less well studied members may also be enriched. We review the implications of these recent studies on future design of prebiotics and synbiotics to promote gastrointestinal health. RECENT FINDINGS: Investigations assessing the clinical outcomes associated with dietary modification of the gut microbiota have shown systemic as well as specific health benefits. Both prebiotic oligosaccharides comprised of a linear arrangement of simple sugars, as well as fiber-rich foods containing complex carbohydrates, have been used in these trials. However, individual variability and nonresponding study participants can make the outcome of dietary interventions less predictable. In contrast, synergistic synbiotics containing prebiotics that specifically stimulate a cognate probiotic provide additional options for personalized gut therapies. SUMMARY: This review describes recent research on how prebiotics and fermentable fibers can influence the gut microbiota and result in improvements to human health. PMID- 26825590 TI - Management of symptom complexes in primary biliary cholangitis. AB - PURPOSE OF REVIEW: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease that increasingly is diagnosed at early stages of disease. Although survival has improved, a majority suffers from one or more symptom complexes associated with PBC. Much remains unknown about the mechanisms, significance, or effective treatment of these symptoms. The present review will outline the latest understanding and management of the most common symptoms of PBC. RECENT FINDINGS: Patients rate fatigue as the most impactful on their quality of life, yet its specificity to PBC remains unsettled. Both central and peripheral nervous system mechanisms have been proposed, but remain enigmatic. Lysophosphatidic acid and G protein-coupled bile acid receptor 1 have emerged as potential targets for cholestatic-specific pathways of pruritus. Fibrates have also shown promise as a new class of antipruritic in cholestatic patients. PBC and Sjogren's syndrome share many demographic and histological features, but the clinical significance of their association is not well understood. SUMMARY: Common symptoms in PBC carry an increasing share of the disease burden as patients live longer, yet existing therapies are frequently ineffective or poorly tolerated. Targeted therapies may emerge as the molecular pathways of PBC-associated symptoms are unraveled. PMID- 26825591 TI - Sleep and academic performance in later adolescence: results from a large population-based study. AB - The aim of the current study was to assess the association between sleep duration and sleep patterns and academic performance in 16-19 year-old adolescents using registry-based academic grades. A large population-based study from Norway conducted in 2012, the youth@hordaland-survey, surveyed 7798 adolescents aged 16 19 years (53.5% girls). The survey was linked with objective outcome data on school performance. Self-reported sleep measures provided information on sleep duration, sleep efficiency, sleep deficit and bedtime differences between weekday and weekend. School performance [grade point average (GPA)] was obtained from official administrative registries. Most sleep parameters were associated with increased risk for poor school performance. After adjusting for sociodemographic information, short sleep duration and sleep deficit were the sleep measures with the highest odds of poor GPA (lowest quartile). Weekday bedtime was associated significantly with GPA, with adolescents going to bed between 22:00 and 23:00 hours having the best GPA. Also, delayed sleep schedule during weekends was associated with poor academic performance. The associations were somewhat reduced after additional adjustment for non-attendance at school, but remained significant in the fully adjusted models. In conclusion, the demonstrated relationship between sleep problems and poor academic performance suggests that careful assessment of sleep is warranted when adolescents are underperforming at school. Future studies are needed on the association between impaired sleep in adolescence and later functioning in adulthood. PMID- 26825593 TI - Usefulness of Percutaneous Transluminal Coronary Balloon Angioplasty for the Left Coronary Artery Stenosis 10 Years More Than After Arterial Switch Operation. AB - Proximal stenosis adjacent to the orifice of one or both coronary arteries may occur after the arterial switch operation (ASO) for d-transposition of the great arteries (d-TGA). Coronary artery stenosis (CAS) often progresses within the first 6 months postoperatively and may result in myocardial ischemia and infarction. Although percutaneous transluminal coronary balloon angioplasty (PCBA) for CAS within 15 months after ASO for d-TGA has been reported, there is no report of PCBA for CAS in the late period after ASO. We present the results of PCBA for CAS of the left coronary artery performed more than 10 years after ASO in an 11-year-old boy and a 14-year-old boy without complication. The stenosis degree improved in both patients from 81 to 45 and 80 to 54 %, respectively. Restenosis did not occur, and the stenosis degree improved to about 25 % late after PCBA. Although the initial effect of PCBA may not be dramatic, it can improve late after PCBA. It was considered that the optimal balloon-reference vessel ratio was about 1.0, to obtain the minimal effective lumen diameter. PCBA for CAS even if performed many years after ASO is feasible without complication. PCBA can also provide delayed improvement late after the procedure. PMID- 26825592 TI - Association between diet-related inflammation, all-cause, all-cancer, and cardiovascular disease mortality, with special focus on prediabetics: findings from NHANES III. AB - INTRODUCTION: Chronic inflammation is associated with increased risk of cancer, cardiovascular disease (CVD), and diabetes. The role of pro-inflammatory diet in the risk of cancer mortality and CVD mortality in prediabetics is unclear. We examined the relationship between diet-associated inflammation, as measured by dietary inflammatory index (DII) score, and mortality, with special focus on prediabetics. METHODS: This prospective cohort study used data from the Third National Health and Nutrition Examination Survey (NHANES III). We categorized 13,280 eligible participants, ages 20-90 years, according to glycosylated hemoglobin (HgbA1c) level and identified 2681 with prediabetes, defined as a glycosylated hemoglobin percentage of 5.7-6.4. Computation of DII scores and all statistical analyses were conducted in 2015. The DII was computed based on baseline dietary intake assessed using 24-h dietary recalls (1988-1994). Mortality was determined from the National Death Index records through 2006. Over follow-up ranging between 135 and 168 person-months, a total of 3016 deaths were identified, including 676 cancer, 192 lung cancer, 176 digestive-tract cancer, and 1328 CVD deaths. Cox proportional hazard regression was used to estimate hazard ratios. RESULTS: The prevalence of prediabetes was 20.19 %. After controlling for age, sex, race, HgbA1c, current smoking, physical activity, BMI, and systolic blood pressure, DII scores in tertile III (vs tertile I) was significantly associated with mortality from all causes (HR 1.39, 95 % CI 1.13, 1.72), CVD (HR 1.44, 95 % CI 1.02, 2.04), all cancers (HR 2.02, 95 % CI 1.27, 3.21), and digestive-tract cancer (HR 2.89, 95 % CI 1.08, 7.71). Findings for lung cancer (HR 2.01, 95 % CI 0.93, 4.34) suggested a likely effect. These results were moderately enhanced after additional adjustment for serum low density lipoprotein and triglyceride and following eliminating deaths during the first year. CONCLUSIONS: A pro-inflammatory diet, as indicated by higher DII scores, is associated with an increased risk of all-cause, CVD, all-cancer, and digestive-tract cancer mortality among prediabetic subjects. PMID- 26825594 TI - Six Medicago truncatula Dicer-like protein genes are expressed in plant cells and upregulated in nodules. AB - KEY MESSAGE: Here we report the existence of six putative Dicer-like genes in the Medicago truncatula genome. They are ubiquitously expressed throughout the plant and significantly induced in root nodules. Over the past decade, small noncoding RNAs (sncRNA) have emerged as widespread and important regulatory molecules influencing both the structure and expression of plant genomes. One of the key factors involved in sncRNA biogenesis in plants is a group of RNase III-type nucleases known as Dicer-like (DCL) proteins. Based on functional analysis of DCL proteins identified in Arabidopsis thaliana, four types of DCLs were distinguished (DCL1-4). DCL1 mainly produces 21 nt miRNAs. The products generated by DCL2, DCL3, and DCL4 belong to various classes of siRNAs that are 22, 24 and 21 nt in length, respectively. M. truncatula is a model legume plant closely related to many economically important cultivable species. By screening the recent M. truncatula genome assembly, we were able to identify three new DCL genes in addition to the MtDCL1-3 genes that had been earlier characterized. The newly found genes include MtDCL4 and two MtDCL2 homologs. We showed that all six M. truncatula DCL genes are expressed in plant cells. The first of the identified MtDCL2 paralogs encodes a truncated version of the DCL2 protein, while the second undergoes substantial and specific upregulation in the root nodules. Additionally, we identified an alternative splicing variant of MtDCL1 mRNA, similar to the one found in Arabidopsis. Our results indicate that DCL genes are differently activated during Medicago symbiosis with nitrogen fixing bacteria and upon pathogen infection. In addition, we hypothesize that the alternative splicing variant of MtDCL1 mRNA may be involved in tissue-specific regulation of the DCL1 level. PMID- 26825597 TI - Programming Life Histories : Creating Individual Differences By The Experimental Control Of Early Experiences. AB - A homogeneous group of rats was exposed to 16 different patterns of experience in early life. These patterns consisted of the following four variables, combined in a 2 X 2 X 2 X 2 factorial design: (a) type of mother, (b) presence or absence of handling in infancy, (c) type of rearing environment preweaning, and (d) postweaning rearing environment. The 16 groups resulting there from may be conceived of as 16 different experimentally created individuals in which the variance among individuals is a function of known experiential inputs during early life. The nature of the design is such that any genetic contribution to individual differences is of a negligible amount. Twenty-three behavioral tests were administered to the 16 groups. Mean scores for each group on each test were intercorrelated and factor analyzed. Six factors were extracted, three of which could be clearly identified as "emotional reactivity," "consumption-elimination," and "field exploration." The results establish that stable and relatively permanent complex individual differences, of the sort often assumed to be genetically determined, can be generated by the appropriate manipulation of experiences during early life. PMID- 26825595 TI - Ectopic expression of phloem motor protein pea forisome PsSEO-F1 enhances salinity stress tolerance in tobacco. AB - KEY MESSAGE: PsSEOF-1 binds to calcium and its expression is upregulated by salinity treatment. PsSEOF - 1 -overexpressing transgenic tobacco showed enhanced salinity stress tolerance by maintaining cellular ion homeostasis and modulating ROS-scavenging pathway. Calcium (Ca(2+)) plays important role in growth, development and stress tolerance in plants. Cellular Ca(2+) homeostasis is achieved by the collective action of channels, pumps, antiporters and by Ca(2+) chelators present in the cell like calcium-binding proteins. Forisomes are ATP independent mechanically active motor proteins known to function in wound sealing of injured sieve elements of phloem tissue. The Ca(2+)-binding activity of forisome and its role in abiotic stress signaling were largely unknown. Here we report the Ca(2+)-binding activity of pea forisome (PsSEO-F1) and its novel function in promoting salinity tolerance in transgenic tobacco. Native PsSEO-F1 promoter positively responded in salinity stress as confirmed using GUS reporter. Overexpression of PsSEO-F1 tobacco plants confers salinity tolerance by alleviating ionic toxicity and increased ROS scavenging activity which probably results in reduced membrane damage and improved yield under salinity stress. Evaluation of several physiological indices shows an increase in relative water content, electrolyte leakage, proline accumulation and chlorophyll content in transgenic lines as compared with null-segregant control. Expression of several genes involved in cellular homeostasis is perturbed by PsSEO-F1 overexpression. These findings suggest that PsSEO-F1 provides salinity tolerance through cellular Ca(2+) homeostasis which in turn modulates ROS machinery providing indirect link between Ca(2+) and ROS signaling under salinity-induced perturbation. PsSEO-F1 most likely functions in salinity stress tolerance by improving antioxidant machinery and mitigating ion toxicity in transgenic lines. This finding should make an important contribution in our better understanding of the significance of calcium signaling in phloem tissue leading to salinity stress tolerance. PMID- 26825598 TI - A Factor Analysis Of Individual Social Desirability Scale Values. AB - The factorial structure of individual judgments of social desirability scale value (SDSV) was studied by factor analyzing a 112 (college students) by 100 (MMPI items) data matrix of individual judgments of SDSV in two ways. One analysis was factoring by item (R technique) while the second analysis was factoring by subject (Q technique). A large general SD factor appeared when subject intercorrelations were factored, but no such general factor was identified when item intercorrelations were factored. Evidence was also presented that the large general SD factor was highly correlated with mean or normative SDSVs. PMID- 26825596 TI - Site-directed mutagenesis in Petunia * hybrida protoplast system using direct delivery of purified recombinant Cas9 ribonucleoproteins. AB - KEY MESSAGE: Site-directed mutagenesis of nitrate reductase genes using direct delivery of purified Cas9 protein preassembled with guide RNA produces mutations efficiently in Petunia * hybrida protoplast system. The clustered, regularly interspaced, short palindromic repeat (CRISPR)-CRISPR associated endonuclease 9 (CRISPR/Cas9) system has been recently announced as a powerful molecular breeding tool for site-directed mutagenesis in higher plants. Here, we report a site directed mutagenesis method targeting Petunia nitrate reductase (NR) gene locus. This method could create mutations efficiently using direct delivery of purified Cas9 protein and single guide RNA (sgRNA) into protoplast cells. After transient introduction of RNA-guided endonuclease (RGEN) ribonucleoproteins (RNPs) with different sgRNAs targeting NR genes, mutagenesis at the targeted loci was detected by T7E1 assay and confirmed by targeted deep sequencing. T7E1 assay showed that RGEN RNPs induced site-specific mutations at frequencies ranging from 2.4 to 21 % at four different sites (NR1, 2, 4 and 6) in the PhNR gene locus with average mutation efficiency of 14.9 +/- 2.2 %. Targeted deep DNA sequencing revealed mutation rates of 5.3-17.8 % with average mutation rate of 11.5 +/- 2 % at the same NR gene target sites in DNA fragments of analyzed protoplast transfectants. Further analysis from targeted deep sequencing showed that the average ratio of deletion to insertion produced collectively by the four NR-RGEN target sites (NR1, 2, 4, and 6) was about 63:37. Our results demonstrated that direct delivery of RGEN RNPs into protoplast cells of Petunia can be exploited as an efficient tool for site-directed mutagenesis of genes or genome editing in plant systems. PMID- 26825599 TI - Year-By-Year Changes In Personality From Six To Eighteen Years. AB - Teacher trait-ratings on 42 bipolar traits were obtained for 660 school children (26 boys and 26 girls from Kindergarten through Grade 12). The trait-ratings were transformed into factor scores on Cattell's 16 basic personality factors. Year-by year cross-sectional analysis of the trait-ratings and factor scores yielded significant sex and age differences throughout the school age period. PMID- 26825600 TI - A Census Tract Analysis Of Socially Deviant Behaviors. AB - In an attempt to study the ecological correlates of various forms of social disequilibrium, census tract characteristics in a moderately large western city were analyzed. Measures of social disequilibrium were found to be highly intercorrelated over tracts. Some community characteristics were identified which bear a significant relationship to these measures of socially deviant behavior. Attention was given to the methodological problems and possibilities in the use of correlational data to suggest cause-effect relationships. PMID- 26825601 TI - Multivariate Analysis Of Gang Delinquency: I. Ecologic Influences. AB - In continuity with delinquency area research, the study examined the neighborhood characteristics of 16 delinquent gangs in Chicago, 1960. Compared with city norms, gang neighborhoods were lower on Borgatta-Hadden census tract factors of Sodo-Economic Status and Stable Family; higher on Disorganization-deprivation; not different on the Suburb factor. Measures of gang behavior were taken from the Short-Tennyson-Howard rated behavior factors: Conflict, Stable Corner-Boy, Mature Sex, Retreatist, and Authority Protest. Significant positive correlations were found between the Suburb and the Stable Corner-Boy factors; and between the Socio Economic Status and Authority Protest factors. These results seem to support two major parts of A. Cohen's theory of delinquent boys. PMID- 26825602 TI - Some Properties Of Three Factor Contribution Matrices. AB - Some properties of three matrices which have been proposed as quantitative bases for factor interpretation are discussed. The first of these contains as elements the covariances of the tests with weighted factor scores. Interpretations of the row sums and column sums of this matrix are given and its independence of the primary factor-reference vector distinction is demonstrated. Two matrices of part correlations are shown to be proportional by columns to the primary factor pattern (and thus to the reference vector structure). One of these matrices is shown to be equal to the reference vector structure. PMID- 26825603 TI - Ordinal Scale Construction For Convergent Validity, Object Discrimination, And Resolving Power. AB - With the use of a weighted consistency coefficient, factor analysis, and criteria for convergent validity, object discrimination, and scale resolving power, an ordinal scale can be uniquely constructed from a set of dichotomous monotone items to most nearly satisfy these criteria. The considerations which are represented in these criteria are necessary constraints for all scale construction. PMID- 26825604 TI - Brief Report: Some Possible Uses Of Factor Analysis In Multivariate Studies. AB - Factor analysis is used in item selection in the hopes of producing a small number of factors each of which will represent a unidimensional sub- scale. If item analysis has been successful in producing truly independent subscales, it might be hoped that the number of factors would equal the number of subscales and that each factor would be highly defined by a single subscale. Factor analysis when used in studies of organization, is not assumed to produce factors that represent unidimensional scales. Rather, factor analysis is used to reveal various substructures that exist within an organization. If several variables are loaded on a single factor, the variables can be regarded as nodes of interaction between measured dimensions of organization. PMID- 26825605 TI - Brief Report : Measures Of Cognitive Structure. AB - Five structural properties of cognition are discussed : domain differentiation, attribute centrality, attribute articulation, affective salience and ambivalence. Several measures of each property are described and convergent validities briefly reported. PMID- 26825606 TI - Hepatocyte nuclear factor 6 inhibits the growth and metastasis of cholangiocarcinoma cells by regulating miR-122. AB - PURPOSE: Hepatocyte nuclear factor 6 (HNF6) is a liver-enriched transcription factor and highly expressed in mature bile duct epithelial cells. This study sought to investigate the role of HNF6, particularly the molecular mechanisms for how HNF6 is involved in the growth and metastasis of cholangiocarcinoma (CCA) cells. METHODS: The expression of HNF6, miR-122 and key molecules was examined by Western blot analysis and real-time RT-PCR. Stable transfectants, HCCC-HNF(low) and RBE-HNF(high), were generated from human CCA HCCC-9810 and RBE cells, respectively. The regulatory effect of HNF6 on miR-122 was evaluated by luciferase reporter assay. Cell proliferation, cycle distribution, migration and invasion were analyzed. The xenograft model was used to assess the effects of HNF6 overexpression on tumorigenesis, growth, metastasis and therapeutic potentials. RESULTS: Human CCA tissues and cells expressed lower levels of HNF6, which positively correlated with miR-122. HNF6 regulated the expression of miR 122 by stimulating its promoter. HNF6 overexpression inhibited cell proliferation by inducing cell cycle arrest at G1 phase through regulating miR-122, cyclin G1 and insulin-like growth factor-1 receptor. HNF6 inhibited the migration and invasion of CCA cells by regulating matrix metalloproteinase-2 and metalloproteinase-9, reversion-inducing-cysteine-rich protein with kazal motifs, E-cadherin and N-cadherin. Co-transfection of anti-miR-122 abrogated the effects of HNF6. HNF6 overexpression inhibited the ability of cells to form tumors and to metastasize to the lungs of mice, and the growth of established tumors. CONCLUSIONS: The results indicate that HNF6 may serve as a tumor suppressor by regulating miR-122, and its overexpression may represent a mechanism-based therapy for CCA. PMID- 26825608 TI - Satisfaction With Methadone Among Heroin-Dependent Patients With Current Substance Use Disorders During Methadone Maintenance Treatment. AB - Methadone maintenance treatment (MMT) has long been used to treat heroin dependent patients. However, satisfaction with methadone in this patient population is unknown. The aim of this cross-sectional case-control study was to evaluate satisfaction with methadone in heroin-dependent patients with current substance use disorders (SUDs). Cases included 152 methadone-maintained patients with current SUD, requiring inpatient detoxification treatment, and controls included 33 methadone-maintained patients in sustained full remission for SUD. Satisfaction with methadone as a medication to treat heroin addiction was measured by using the Scale to Assess Satisfaction with Medications for Addiction Treatment-methadone for heroin addiction (SASMAT-METHER). The SASMAT-METHER subscales assess the following domains: personal functioning and well-being, antiaddictive effect on heroin, and antiaddictive effect on other substances. Compared with patients with remitted SUD, patients with current SUD scored lower on all SASMAT-METHER assessments. In such patients, overall SASMAT-METHER scores were independently and negatively associated with downward desired adjustment of methadone dose and days of heroin use during last month; although various sets of factors were independently associated with each of the SASMAT-METHER subscales, the only determinant of dissatisfaction on all subscales was the desire for downward adjustment of methadone dose. In summary, MMT patients with current SUD are less satisfied with methadone than MMT patients with remitted SUD. In patients with current SUD, downward desired adjustment of methadone dose and days of heroin use during last month are independently associated with overall dissatisfaction with methadone. PMID- 26825609 TI - Transpapillary selective bile duct cannulation technique: Review of Japanese randomized controlled trials since 2010 and an overview of clinical results in precut sphincterotomy since 2004. AB - In 1970, a Japanese group reported the first use of endoscopic retrograde cholangiopancreatography (ERCP), which is now carried out worldwide. Selective bile duct cannulation is a mandatory technique for diagnostic and therapeutic ERCP. Development of the endoscope and other devices has contributed to the extended use of ERCP, which has become a basic procedure to diagnose and treat pancreaticobiliary diseases. Various techniques related to selective bile duct cannulation have been widely applied. Although the classical contrast medium injection cannulation technique remains valuable, use of wire-guided cannulation has expanded since the early 2000s, and the technique is now widely carried out in the USA and Europe. Endoscopists must pay particular attention to a patient's condition and make an attendant choice about the most effective technique for selective bile duct cannulation. Some techniques have the potential to shorten procedure time and reduce the incidence of adverse events, particularly post-ERCP pancreatitis. However, a great deal of experience is required and endoscopists must be skilled in a variety of techniques. Although the development of the transpapillary biliary cannulation approach is remarkable, it is important to note that, to date, there have been no reports of transpapillary cannulation preventing post-ERCP pancreatitis. In the present article, selective bile duct cannulation techniques in the context of recent Japanese randomized controlled trials and cases of precut sphincterotomy are reviewed and discussed. PMID- 26825607 TI - Disseminated and circulating tumor cells in bone marrow and blood of breast cancer patients: properties, enrichment, and potential targets. AB - INTRODUCTION: From the early days of pathology back in the nineteenth century until now, there has been an ongoing search for the missing link between solid tumors such as breast cancer and distant metastases, which sometimes occur many years after removal of the primary tumor. The "seed and soil" theory hypothesizes the early dissemination of occult tumor cells into blood or bone marrow, which can persist in a dormant state for a long time and then become precursors of metastases in distant organs which offer appropriate conditions. METHOD: Advances in immunocytochemical methods have enabled the enrichment and visualization of those disseminated tumor cells in bone marrow (DTC-BM) or circulating tumor cells (CTC) in blood. Many studies could demonstrate prognostic significance of the detection of DTC-BM or CTC in different stages of breast cancer. CONCLUSION: Further characterization of those cells by immunocytochemical stainings, fluorescence in situ hybridizations, or PCR-based molecular methods will help to understand the biology of tumor cell dissemination and metastasis formation, as well as to define potential drug targets. PMID- 26825610 TI - Methods of Monitoring Cell Fate and Tissue Growth in Three-Dimensional Scaffold Based Strategies for In Vitro Tissue Engineering. AB - In the field of tissue engineering, there is a need for methods that allow assessing the performance of tissue-engineered constructs noninvasively in vitro and in vivo. To date, histological analysis is the golden standard to retrieve information on tissue growth, cellular distribution, and cell fate on tissue engineered constructs after in vitro cell culture or on explanted specimens after in vivo applications. Yet, many advances have been made to optimize imaging techniques for monitoring tissue-engineered constructs with a sub-mm or MUm resolution. Many imaging modalities have first been developed for clinical applications, in which a high penetration depth has been often more important than lateral resolution. In this study, we have reviewed the current state of the art in several imaging approaches that have shown to be promising in monitoring cell fate and tissue growth upon in vitro culture. Depending on the aimed tissue type and scaffold properties, some imaging methods are more applicable than others. Optical methods are mostly suited for transparent materials such as hydrogels, whereas magnetic resonance-based methods are mostly applied to obtain contrast between hard and soft tissues regardless of their transparency. Overall, this review shows that the field of imaging in scaffold-based tissue engineering is developing at a fast pace and has the potential to overcome the limitations of destructive endpoint analysis. PMID- 26825611 TI - Heterozygous Chorein Deficiency in Probable Tau-negative Early-onset Alzheimer Disease. PMID- 26825612 TI - Resection of portal and/or superior mesenteric vein and reconstruction by using allogeneic vein for pT3 pancreatic cancer. AB - BACKGROUND AND AIM: There is still controversy on the outcomes of portal vein (PV) and/or superior mesenteric vein (SMV) resection in pancreatic cancer, and there are few reports about pancreaticoduodenectomy (PD) with PV/SMV resection and reconstruction by using allogeneic vein. This study is to explore the outcomes of PD with PV/SMV resection and reconstruction by using allogeneic vein for pT3 pancreatic cancer with venous invasion. METHODS: Clinicopathological data of patients underwent PD with en bloc resection of PV/SMV and reconstruction by using internal iliac from August 20, 2013 to July 25, 2015 were collected and the data of patients with pT3 stage pancreatic head cancer with PV/SMV invasion were analyzed. The short- and long-term outcomes were presented. RESULTS: Thirty patients met the criteria of this study. PV resection and reconstruction were performed for 12 patients, SMV for 9 patients, and PV + SMV for 9 patients, respectively. The median operation time was 460 min, and the median intraoperative blood loss was 450 mL. R0 resection rate was 93.3%, total incidence of complications was 23.3%, and incidence of pancreatic fistula was 10%. The 1-year and 2-year overall survival rates were 68.6% and 39.2%, 1-year and 2-year disease free survival rates were 44.8% and 17.1%. CONCLUSIONS: PD with en bloc resection of PV/SMV and reconstruction by using allogeneic vein was safe and feasible for patients with pT3 stage pancreatic head cancer with PV/SMV invasion. A large-scale research with longer follow-up time is required to draw a significant conclusion. PMID- 26825613 TI - Older patients with traumatic brain injury present with a higher GCS score than younger patients for a given severity of injury. AB - INTRODUCTION: Recent evidence suggests that presenting GCS may be higher in older rather than younger patients for an equivalent anatomical severity of traumatic brain injury (TBI). The aim of this study was to confirm these observations using a national trauma database and to test explanatory hypotheses. METHODS: The Trauma Audit Research Network database was interrogated to identify all adult cases of severe isolated TBI from 1988 to 2013. Cases were categorised by age into those under 65 years and those 65 years and older. Median presenting GCS was compared between the groups at abbreviated injury score (AIS) level (3, 4 and 5). Comparisons were repeated for subgroups defined by mechanism of injury and type of isolated intracranial injury. RESULTS: 25 082 patients with isolated TBI met the inclusion criteria, 10 936 in the older group and 14 146 in the younger group. Median or distribution of presenting GCS differed between groups at each AIS level. AIS 3: 14 (11-15) vs 15 (13-15), AIS 4: 14 (9-15) vs 14 (13-15), AIS 5: 9 (4-14) vs 14 (5-15) all p<0.001. Similar differences between the groups were observed across all mechanisms of injury and types of isolated intracranial injury. We detected no influence of gender on results. CONCLUSIONS: For an equivalent severity of intracranial injury, presenting GCS is higher in older patients than in the young. This observation is unlikely to be explained by differences in mechanism of injury or types of intracranial injury between the two groups. PMID- 26825614 TI - Factors associated with poor knowledge among adults on tuberculosis in Bangladesh: results from a nationwide survey. AB - INTRODUCTION: In 2012, Bangladesh continues to be one of the 22 high tuberculosis (TB) burden countries in the world. Although free diagnosis and management for TB is available throughout the country, case notification rate/100,000 population for new smear positive (NSP) cases under the national TB control programme (NTP) remained at around 70/100,000 population and have not changed much since 2006. Knowledge on TB disease, treatment and its management could be an important predictor for utilization of TB services and influence case detection under the NTP. Our objective is to describe knowledge of TB among newly diagnosed TB cases and community controls to assess factors associated with poor knowledge in order to identify programmatic implications for control measures. METHODS: Embedded in TB prevalence survey 2007-2009, we included 240 TB cases from the TB registers and 240 persons >= 15 years of age randomly selected from the households where the survey was implemented. All participants were interviewed using a structured, pre-tested questionnaire to evaluate their TB knowledge. Regression analyses were done to assess associations with poor knowledge of TB. RESULTS: Our survey documented that overall there was fair knowledge in all domains investigated. However, based on the number of correct answers to the questionnaires, community controls showed significantly poorer knowledge than the TB cases in the domains of TB transmission (80% vs. 88%), mode of transmission (67% vs. 82%), knowing >= 1 suggestive symptoms including cough (78% vs. 89%), curability of TB (90% vs. 98%) and availability of free treatment (75% vs. 95%). Community controls were more likely to have poor knowledge of TB issues compared to the TB cases even after controlling for other factors such as education and occupation in a multivariate model (OR 3.46, 95% CI: 2.00-6.09). CONCLUSIONS: Knowledge on various aspects of TB and TB services varies significantly between TB cases and community controls in Bangladesh. The overall higher levels of knowledge in TB cases could identify them as peer educators in ongoing communication approaches to improve care seeking behavior of the TB suspects in the community and hence case detection. PMID- 26825615 TI - A patient group at negligible risk of para-aortic lymph node metastasis in endometrial cancer. AB - OBJECTIVE: The objective of this study was to identify a group at negligible risk of para-aortic lymph node metastasis (LNM) in endometrial cancer and its presumed prognosis. METHODS: We enrolled 555 patients with endometrial cancer who underwent preoperative endometrial biopsy, pelvic magnetic resonance imaging, and determination of serum cancer antigen (CA)125, and surgical treatment including lymphadenectomy. Three risk factors for LNM confirmed in previous reports were grade 3/non-endometrioid histology, large tumor volume, and a high CA125 value. Pelvic LNM rate, para-aortic LNM rate, and 5-year overall survival rate were assessed in four groups according to the number of these risk factors. RESULTS: LNM was noted in medical records of 74 patients (13.3%). Of 226 patients in the no risk factor group, pelvic LNM was noted in the medical records of five (2.2%), but no para-aortic LNM was noted. The 3-year/5-year survival rates in the no risk factor group were 97.2/96.6%, with a median follow-up period of 65.5 months. Of 186 patients in the one risk factor group, 21 (11.2%) had pelvic LNM. Of 113 patients undergoing para-aortic LN dissection in the one risk factor group, six (5.3%) had para-aortic LNM. CONCLUSION: Patients with grade 1/2 histology based on endometrial biopsy, small tumor volume assessed by magnetic resonance imaging, and low CA125 value are supposed to have negligible risk of para-aortic LNM. In such patients, the para-aortic region might not be considered as a target to be assessed by staging procedure. PMID- 26825616 TI - Primary surgical cytoreduction in advanced ovarian cancer: An outcome analysis within the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) Group. AB - OBJECTIVE: To draw a reliable picture of the surgical management of advanced ovarian cancer (AOC) within the MITO Group, trying to correlate the disease extent at presentation, the category of center, and surgical outcome. METHODS: Three tertiary referral centers for gynecologic oncology and four non-oncologic referral gynecologic surgical centers, participated in the project. A questionnaire was adopted to register perioperative data on AOCs (FIGO Stage IIICIV) consecutively operated on for a period of 12months. RESULTS: A total of 205 patients were registered into the study: 140 and 65 were recruited in oncological referral centers and non-referral centers, respectively. Following a multivariate analysis, the Eisenkop score and the category of center resulted the most potent predictors of complete surgical cytoreduction followed by PCI, preoperative CA125, and ASA score. Complete surgical cytoreduction was associated with oncological referral centers (60% vs 24.6%, p<0.001). The proportion of patients undergoing additional surgical procedures was significantly different comparing the two categories of centers (at least one additional procedure was performed in 81.4% vs 50.8% in oncological referral centers compared to the others, p<0.001). Despite the more aggressive surgery performed in oncological referral centers, the perioperative outcome measures were not significantly different in the two groups. CONCLUSIONS: The chance of obtaining a complete cytoreduction mainly depends on patient characteristics, tumor spread, and quality of treatment. The latter is amenable for direct influence, and therefore, seems to be of utmost importance when considering efforts aiming at improvement in the outcome of this disease. PMID- 26825617 TI - Comparing the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA): Two equivalent ways to differentiate malignant from benign ovarian tumors before surgery? AB - AIM: To evaluate the prediction of malignancy in women with pelvic masses using the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA). PATIENTS AND METHODS: Three hundred eighty four women operated due to an ovarian mass were enrolled between January 2010 and June 2015. All patients had histopathological diagnosis, HE4 and CA125 measurement. CPH-I and ROMA were calculated and their performances compared in two distinct scenarios: 1) for the discrimination of benign ovarian disease from epithelial ovarian cancer (EOC), non-epithelial ovarian cancer, borderline ovarian tumors (BOT) and ovarian metastases, and 2) for the discrimination of benign disease from EOC. Receiver Operator Characteristics' Areas Under the Curves (AUC) were calculated for CPH-I and ROMA and compared. RESULTS: Of the 384 women, 224 presented a benign ovarian tumor, 32 BOT, 87 EOC, 26 non-epithelial ovarian cancer, and 15 had ovarian metastases. The best AUCs were obtained for the discrimination of EOC from benign tumors. CPH-I performed slightly better than ROMA, and both approached 89% sensitivity and 85% specificity. When all malignant tumors (EOC, BOT, ovarian metastases and non-epithelial ovarian cancer - entire cohort) were included, the performance of CPH-I and ROMA declined to nearly 72%, although the specificity remained close to 85%. CONCLUSION: CPH-I and ROMA performed similarly well for the discrimination of EOC from benign ovarian tumors. However, caution is necessary since, in practical situations, where all the histological possibilities for malignant ovarian tumors must be considered, the sensitivity of CPH-I and ROMA may not surpass 70%. PMID- 26825618 TI - Chronotype, Light Exposure, Sleep, and Daytime Functioning in High School Students Attending Morning or Afternoon School Shifts: An Actigraphic Study. AB - Adolescent maturation is associated with delays of the endogenous circadian phase. Consequently, early school schedules may lead to a mismatch between internal and external time, which can be detrimental to adolescent sleep and health. In parallel, chronotype is known to play a role in adolescent health; evening chronotype adolescents are at higher risk for sleep problems and lower academic achievement. In the summer of 2008, Kenogami High School (Saguenay, Canada) was destroyed by fire. Kenogami students were subsequently relocated to Arvida High School (situated 5.3 km away) for the 2008-2009 academic year. A dual school schedule was implemented, with Arvida students attending a morning schedule (0740-1305 h) and Kenogami students an afternoon schedule (1325-1845 h). This study aimed to investigate the effects of such school schedules and chronotype on sleep, light exposure, and daytime functioning. Twenty-four morning and 33 afternoon schedule students wore an actigraph during 7 days to measure sleep and light exposure. Academic achievement was obtained from school. Subjects completed validated questionnaires on daytime sleepiness, psychological distress, social rhythms, school satisfaction, alcohol, and chronotype. Overall, afternoon schedule students had longer sleep duration, lower sleepiness, and lower light exposure than morning schedule students. Evening chronotypes (E-types) reported higher levels of sleepiness than morning chronotypes (M-types) in both morning and afternoon schedules. Furthermore, M-types attending the morning schedule reported higher sleepiness than M-types attending the afternoon schedule. No difference was found between morning and afternoon schedule students with regard to academic achievement, psychological distress, social rhythms, school satisfaction, and alcohol consumption. However, in both schedules, M-type had more regular social rhythms and lower alcohol consumption. In summary, this study emphasizes that an early school schedule is associated with detrimental effects in terms of sleep deprivation and daytime sleepiness, even for M-types. Furthermore, irrespective of school schedule, E-type adolescents face an increased risk for poor daytime functioning. PMID- 26825620 TI - Sepsis in Pregnancy: Identification and Management. AB - Sepsis accounts for up to 28% of all maternal deaths. Prompt, appropriate treatment improves maternal and fetal morbidity and mortality. To date, there are no validated tools for identification of sepsis in pregnant women, and tools used in the general population tend to overestimate mortality. Once identified, management of pregnancy-associated sepsis is goal-directed, but because of the lack of studies of sepsis management in pregnancy, it must be assumed that modifications need to be made on the basis of the physiologic changes of pregnancy. Key to management is early fluid resuscitation and early initiation of appropriate antimicrobial therapy directed toward the likely source of infection or, if the source is unknown, empiric broad-spectrum therapy. Efforts directed at identifying the source of infection and appropriate source control measures are critical. Development of an illness severity scoring system and treatment algorithms validated in pregnant women needs to be a research priority. PMID- 26825619 TI - Anterior Insula Regulates Multiscale Temporal Organization of Sleep and Wake Activity. AB - The role of specific cortical regions in sleep-regulating circuits is unclear. The anterior insula (AI) has strong reciprocal connectivity with wake and sleep promoting hypothalamic and brainstem regions, and we hypothesized that the AI regulates patterns of sleep and wakefulness. To test this hypothesis, we lesioned the AI in rats (n = 8) and compared sleep, wake, and activity regulation in these animals with nonlesioned controls (n = 8) with 24-h sleep recordings and chronic infrared activity monitoring. Compared to controls, animals with AI lesions had decreased wakefulness and increased rapid eye movement (REM) sleep and non-REM (NREM) sleep. AI-lesioned animals had shorter wake bouts, especially during the active dark phase. AI-lesioned animals also had more transitions from NREM to REM sleep, especially during the inactive light phase. Chronic infrared monitoring revealed that AI-lesioned animals also had a disturbed temporal organization of locomotor activity at multiple time scales with more random activity fluctuations from 4 to 12 h despite intact circadian rhythms. These results suggest that the AI regulates sleep and activity and contributes to the regulation of sleep and motor behavior rhythmicity across multiple time scales. Dysfunction of the AI may underlie changes in sleep-wake patterns in neurological diseases. PMID- 26825621 TI - Severe postthrombotic syndrome is associated with characteristic sonographic pattern of the residual thrombosis. AB - Postthrombotic syndrome (PTS) may affect 50% of patients with deep venous thrombosis, 5-10% of them may present severe manifestations. The causes for PTS development and severity have not been well established. This study evaluated whether PTS may be associated with the presence, and echogenicity, of the residual vein thrombosis (RVT). We included patients with a history of deep venous thrombosis in the past 58 months. These patients were further evaluated for PTS diagnosis, clinical comorbidities, plasma levels of D-dimer, serum levels of C-reactive protein and for the presence of RVT. Particularly, RVT was detected by ultrasound examination and the residual thrombi echogenicity was determined by grayscale median (GSM). Fifty-six patients were included, of which 41 presented PTS. Mild PTS was detected in 23 patients, moderate PTS in 11 and severe PTS in seven patients. Patients with severe PTS showed higher body mass index, higher abdominal circumference and higher C-reactive protein levels when compared with the other patients (P = 0.007, P = 0.002, P = 0.02, respectively). The ultrasound generated GSM was significantly lower in patients with severe PTS compared with patients with mild-moderate PTS or no PTS (median = 24, 35 and 41, respectively; P = 0.04). A GSM value less than 25, which was consistent with a hypoechoic RVT, was the best cut-off value to discriminate patients with severe PTS from those with mild or moderate PTS and those without PTS. RVT is a common finding among patients with PTS and the echogenicity of the RVT may impact the severity of PTS. PMID- 26825622 TI - The influence of immunoglobulin class G from blood plasma of patients with stroke on the activity of some parameters of hemostasis system. AB - Today, cardiovascular diseases are one of the main causes of disability of the population. Most of the illnesses, including stroke, are accompanied by the appearance immunoglobulin G (IgG) in the blood circulation. According to the literature sources and previous experiments, it is known that IgG made influence on the hemostasis system. Objectives of the investigation are pure enzymes: thrombin, factor X, proenzyme of protein C and prothrombin under the influence of IgG fraction that were separated from the plasma of patients with atherothrombotic and cardioembolic ischemic stroke and patients with other neurological diseases. IgG was separated by affinity chromatography. Disc electrophoresis was used to control antibodies' purity. The main goal of the experiment is to test the potential influence of all fractions of separated IgG on the process of hydrolysis of specific chromogenic substrates by the key factors of the hemostasis system such as thrombin, factor X and protein C. The appearance of IgG in the blood stream during the atherothrombotic and cardioembolic ischemic stroke and other neurological diseases was proved. Concentration of the IgG in plasma of patients with cardioembolic ischemic stroke was significantly higher compared with healthy donors, whereas the IgG in plasma of patients with atherothrombotic ischemic stroke and other neurological disorders was not significantly different. Their potential ability to influence the enzymes such as thrombin, factor X, proenzyme of protein C and prothrombin was shown. It was proved that the antibody fractions of all experimental groups significantly accelerate the process of splitting chromogenic substrate by thrombin but inhibited cleavage of a specific chromogenic substrate by protein C. PMID- 26825623 TI - Vitamin D deficiency and osteoporosis in hemophilic children: an intermingled comorbidity. AB - The aim of this study is to investigate bone state and factors affecting it in children with hemophilia. This is a case-control study that included 37 children with hemophilia and 37 healthy controls. The patients were selected from the outpatient pediatric hematology clinic of Fayoum University Hospital, Egypt. Bone mineral density, serum vitamin D, parathormone, calcium, phosphorus, and calcium creatinine ratio levels were evaluated. Vitamin D level and bone mineral density were significantly lower in hemophiliacs than in control group (P < 0.0001). About 43.2% of cases had moderate vitamin D deficiency, whereas 35.1% had mild deficiency. Vitamin D positively correlated with bone mineral density Z-score, whereas it negatively correlated with total joint score. Positive correlation between bone mineral density and age was also found. Serum levels of urea, urinary calcium creatinine ratio, and parathormone were found to be higher in cases than in control. Also, serum calcium level was found to be lower in patients than in controls. We concluded that vitamin D deficiency is an essential cause of decreased bone mineral density in hemophilic children. Hemophilic arthropathy with consecutive immobilization plays an important role in vitamin D deficiency and decreased bone mineral density. PMID- 26825624 TI - Perioperative ROTEM and ROTEMplatelet monitoring in a case of Glanzmann's thrombasthenia. AB - Glanzmann's thrombasthenia is a rare, inherited disease, which consists in abnormality of the glycoprotein IIa/IIIb genes that causes impaired platelet function. Glanzmann's thrombasthenia patients show prolongation of bleeding time and may experience life-threatening hemorrhage after surgery. We present a case of a young woman having Glanzmann's thrombasthenia, who underwent gynecological operation for ovarian cyst. Perioperative monitoring included thromboelastometry with ROTEM and impedance aggregometry with ROTEMplatelet. In this case, despite acceptable ROTEM results after platelet transfusion, ROTEMplatelet was more indicative of hemostatic impairment and reflected the bleeding occurred in the postoperative period. When treating patients with congenital or acquired platelet dysfunction, some intrinsic limits of thromboelastometry to assess platelet function may be overcome with the combined use of a point-of-care device that measures platelet aggregation. PMID- 26825625 TI - Laboratory evaluation of patients with undiagnosed bleeding disorders. AB - The evaluation of patients with a bleeding tendency represents a challenge as the routinely available tests for evaluating bleeding disorders are limited, complicating the laboratory determination of the clinically observed bleeding tendency. As a result, some bleeding disorders remain undiagnosed. The aim of the study was to evaluate whether global coagulation tests would contribute to the laboratory analysis of patients with undiagnosed bleeding disorders. Patients were evaluated for coagulation and fibrinolysis activities by thrombin generation test and euglobulin lysis time. In addition, plasma activity of factor XIII, plasminogen, alpha-2 antiplasmin, plasminogen activator inhibitor-1, and thrombin activatable fibrinolysis inhibitor was also obtained. Forty-five patients were included. Eight per cent presented a mild bleeding disorder and 20% a moderate bleeding disorder. The thrombin generation test results were similar between patients and controls. Euglobulin lysis time results, however, were lower in patients than in controls, both before (median 175 vs. 250 min, respectively; P = 0.003) and after (median 145 vs. 115 min, respectively; P <= 0.001) arm constriction, suggesting that they were experiencing hyperfibrinolysis. Interestingly, patients' median thrombin-activatable fibrinolysis inhibitor activity was higher than in controls (21.2 vs. 19.46 MUg/ml; P = 0.016). However, plasminogen, alpha-2 antiplasmin, plasminogen activator inhibitor-1, and factor XIII activities did not differ between the groups. Global coagulation and fibrinolysis tests proved to be limited in detecting the hemostatic disorders in some patients with a relevant bleeding tendency and may not be adequate to address their bleeding risk. Bleeding scores are currently the available medical approach for the evaluation of these patients. PMID- 26825626 TI - Is there a relationship between platelet parameters and patency of ductus arteriosus in preterm infants? AB - Postnatal closure of the ductus arteriosus is a complicated two-phase process involving functional and structural changes. So far, the precise mechanisms regulating this process are not fully understood. A growing body of evidence from recent studies suggests that platelets play a key role in inflammatory processes including ductal closure via interaction with endothelial cells. The aim of this study is to assess whether a relationship exists between the occurrence and/or closure of hemodynamically significant ductus arteriosus (HSDA) and platelet parameters (platelet count, circulating platelet mass, mean platelet volume, platelet distribution width) in preterm newborns. This single-center, retrospective study included 824 premature infants between 24 and 34 gestational weeks, evaluated by echocardiography at postnatal 72-96 h. Infants with and without HSDA (n = 208 vs. n = 616) were compared in terms of platelet parameters recorded within the first 3 days of life. Oral or intravenous ibuprofen was commenced for medical treatment, and echocardiography was repeated 24 h thereafter to determine ductal closure. No statistically significant difference could be demonstrated between the groups in terms of baseline platelet parameters. HSDA was independently associated with early-onset neonatal sepsis. Thrombocytopenia, low circulating platelet mass, high platelet distribution width, or high mean platelet volume could not be demonstrated as a risk factor for HSDA. None of the platelet parameters had an influence on ductal closure after medical treatment. Unlike most reports in the literature, presence of HSDA was not associated with any platelet parameter in our study. We could not demonstrate an association between any platelet parameter and either persistence or closure after medical treatment. PMID- 26825627 TI - Activity levels of natural anticoagulant proteins in childhood acute lymphoblastic leukemia: relation to thromboembolic complications and treatment. AB - Thromboembolism is a well recognized life-threatening complication in childhood acute lymphoblastic leukemia (ALL). Proper and early diagnosis of thromboembolism is of paramount importance to reduce mortality and morbidity. We evaluated antithrombin III (ATIII), protein C, protein S, and D-dimer in 60 children with ALL compared with 30 healthy controls, and patients were followed up for 12 months for detection of thrombotic complications. The relation between these natural anticoagulants and the development of thrombotic complications, as well as therapy was assessed to identify patients at risk of thromboembolism. ATIII, protein C, and protein S were significantly reduced (P < 0.001) with elevated D dimer (P < 0.001) in patients with ALL compared with those in the control group. The incidence of thrombotic complications was 16.7%. Patients with thrombotic complications had significantly lower ATIII, protein C, protein S, and platelet count, whereas age, total leukocyte count, and D-dimer were increased compared with those without thrombosis (P < 0.05). Patients under chemotherapy had lower ATIII, protein C, and protein S levels with higher D-dimer compared with the newly diagnosed untreated patients (P < 0.05). ATIII and protein C were positively correlated (r = 0.573, P = 0.002), whereas both were negatively correlated with D-dimer (P < 0.001). ALL is associated with a state of hypercoagulability, which may be attributed to hemostatic derangement because of increased thrombin generation indicated by elevated D-dimer in association with decreased natural anticoagulants ATIII, protein C, and protein S. ALL children during induction/consolidation phase of chemotherapy are at high risk of developing thromboembolism complications and the prophylactic use of anticoagulant should be considered. PMID- 26825628 TI - Primary thrombophilia in Mexico: a single tertiary referral hospital experience. AB - Thrombophilia is a complex hypercoagulable state that increases the risk of thrombosis. Most reports in medical literature of the Mexican population with this disease lack statistical validity. Therefore, the aim of this study is to describe the prevalence of primary thrombophilia in a tertiary referral hospital in Mexico. This is a study of patients referred to our hospital because of a hypercoagulable state and who later on were diagnosed with primary thrombophilia. The thrombophilia workup included methylenetetrahydrofolate reductase (MTHFR) C677T, antiphospholipid antibodies, protein C, protein S, antithrombin, factor VIII, factor V Leiden, prothrombin mutation G20210A, activated protein C resistance, JAK2 V617F and homocysteine. Ninety-five individuals were tested. The MTHFR C677T polymorphism was the most frequent anomaly in 84.1% of the tested individuals. There was a relatively low prevalence of factor V Leiden (5.2%) and anticoagulant protein deficiency (8.3%). The MTHFR C677T polymorphism has a very high prevalence compared with the low prevalence of anticoagulant protein deficiency and factor V Leiden mutation in Mexicans. PMID- 26825629 TI - Kinetics and molecular docking studies of fucosterol and fucoxanthin, BACE1 inhibitors from brown algae Undaria pinnatifida and Ecklonia stolonifera. AB - Since the action of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is strongly correlated with the onset of Alzheimer's disease (AD), the development of BACE1 inhibitors as therapeutic agents is being vigorously pursued. In our ongoing research aimed at identifying anti-AD remedies derived from maritime plants, we evaluated the BACE1 inhibitory activities of fucosterol and fucoxanthin from Ecklonia stolonifera and Undaria pinnatifida. In vitro anti AD activities were performed via BACE1 inhibition assays, as well as enzyme kinetic and molecular docking predictions. Based on enzyme-based assays, fucosterol and fucoxanthin showed noncompetitive and mixed-type inhibition, respectively, against BACE1. In addition, docking simulation results demonstrated that the Lys224 residue of BACE1 interacted with one hydroxyl group of fucosterol, while two additional BACE1 residues (Gly11 and Ala127) interacted with two hydroxyl groups of fucoxanthin. Moreover, the binding energy of fucosterol and fucoxanthin was negative (-10.1 and -7.0 kcal/mol), indicating that hydrogen bonding may stabilize the open form of the enzyme and potentiate tight binding of the active site of BACE1, resulting in more effective BACE1 inhibition. The results suggest that fucosterol and fucoxanthin may be used beneficially in the treatment of AD and provide potential guidelines for the design of new BACE1 inhibitors. PMID- 26825631 TI - Notch signaling in the epididymal epithelium regulates sperm motility and is transferred at a distance within epididymosomes. AB - Spermatozoa undergo sequential maturation changes during their transit along the epididymis. These changes are modulated by the epididymal epithelium and require a finely tuned gene expression. The Notch cell signaling pathway is a major regulator of cell fate decisions in several tissues, including the testis. Here, we evaluated the transcription and expression patterns of Notch components (Notch1-3, Dll1, Dll4, and Jagged1) and effectors (Hes1-2 and Hes5) in the adult mouse epididymis, and evaluated the role of Notch signaling in the epididymis through its in vivo blockade following administration of an inhibitor (DAPT). Notch components and effectors were dynamically transcribed and expressed in the epididymis and vas deferens, each segment exhibiting a specific combination of epithelial receptor/ligand/effector expression patterns. Nuclear detection of Notch effectors indicates that Notch signaling was active. Notch components (but not effectors) were identified in the cytoplasmic droplet of spermatozoa, in a dynamic and specific pattern along the epididymis. In addition, Notch components were identified within large and small vesicles in the epididymal lumen. A purified population of these membranous vesicles from different epididymal segments was obtained, and through dot blot analysis, it was confirmed that Notch components were carried within these vesicles in a dynamic pattern along the epididymal lumen. We hypothesize that these vesicles (epididymosomes) allow Notch signaling at distance from epididymal epithelial cells to spermatozoa. DAPT induced in vivo Notch signaling blockade, although showing a low efficiency, disrupted the expression patterns of Notch components and effectors in the epididymal epithelium and in spermatozoa, and significantly decreased sperm motility, although not affecting male fertility. These results prompt for a regulatory role of Notch signaling in epididymal epithelial function and sperm maturation. PMID- 26825630 TI - Self-reported psychological demands, skill discretion and decision authority at work: A twin study. AB - OBJECTIVES: To examine the contribution of genetic factors to self-reported psychological demands (PD), skill discretion (SD) and decision authority (DA) and the possible importance of such influence on the association between these work variables and depressive symptoms. METHODS: 11,543 participants aged 27-54 in the Swedish Twin Registry participated in a web survey. First of all, in multiple regressions, phenotypic associations between each one of the three work environment variables and depressive symptoms were analysed. Secondly, by means of classical twin analysis, the genetic contribution to PD, SD and DA was assessed. After this, cross-twin cross-trait correlations were computed between PD, SD and DA, on the one hand, and depressive symptom score, on the other hand. RESULTS: The genetic contribution to self-reported PD, DS and DA ranged from 18% for decision authority to 30% for skill discretion. Cross-twin cross-trait correlations were very weak (r values < .1) and non-significant for dizygotic twins, and we lacked power to analyse the genetic architecture of the phenotypic associations using bivariate twin modelling. However, substantial genetic contribution to these associations seems unlikely. CONCLUSIONS GENETIC CONTRIBUTIONS TO THE SELF-REPORTED WORK ENVIRONMENT SCORES WERE 18-30%. PMID- 26825634 TI - Fully Balanced Fluids do not Improve Microvascular Oxygenation, Acidosis and Renal Function in a Rat Model of Endotoxemia. AB - The expectation of fluid therapy in patients with septic shock is that it corrects hypovolemia, with the aim of restoring tissue perfusion and oxygenation and organ function. This study investigated whether different types of resuscitation fluids were effective in improving renal microcirculatory oxygenation, acidosis, oxidative stress, and renal function in a rat model of endotoxemic shock. Five groups of rats were used: a sham group, a lipopolysaccharide (LPS) group, and three LPS groups that received 30 mL/kg/h of 0.9% sodium chloride (0.9% NaCl), a new bicarbonate buffered crystalloid solution closely resembling the composition of plasma (FB-Cxt) or a hydroxyethyl starch ringer acetate solution. Systemic hemodynamic variables, renal blood flow, microvascular oxygenation, oxidative/nitrosative stress, and renal function were measured. LPS-induced shock was only partially resolved by fluid administration. Animals became arterially hypotensive despite adequate central venous pressure. Hydroxyethyl starch-ringer acetate was more effective at improving arterial pressures and renal blood flow than 0.9% NaCl or FB-Cxt. Fluids had marginal effects on pH and HCO3 levels irrespective of the buffer, or on renal MUPO2 and dysfunction. Colloids increased the markers of renal oxidative stress (P < 0.001), whereas unbalanced crystalloids increased the markers of nitrosative stress during sepsis (P < 0.01). Endotoxemia-induced acidosis and decreases in renal MUPO2 or renal injury were not corrected solely by fluid resuscitation, irrespective of the buffer of the fluid. Our study supported the idea that fluids must be supplemented by other compounds that specifically correct renal inflammation and oxygenation to be effective in resolving septic shock-induced renal failure. PMID- 26825633 TI - [Therapy with blood products]. AB - Blood products are frequently used in intensive care medicine although there is little evidence of improvement in clinical outcome. The threshold for erythrocyte transfusion in non-bleeding critically ill patients is currently a hemoglobin level of 7.0 g/dl. The indications for platelet transfusion must be assessed after evaluation of the cause of thrombocytopenia, the clinical condition and the expected effect. The use of plasma should also be critically viewed, mainly due to hypervolemia. Prothrombin complex concentrates are better than plasma for warfarin reversal. There is good evidence for the use of albumin for massive paracentesis, in the treatment of hepatorenal syndrome type 1 and spontaneous bacterial peritonitis. Albumin infusion can have favorable effects in severe sepsis and septic shock. A restrictive strategy should be favored in the use of blood products and the decision should be based on a critical appraisal of the available evidence. PMID- 26825635 TI - Prehospital Blood Product Resuscitation for Trauma: A Systematic Review. AB - INTRODUCTION: Administration of high ratios of plasma to packed red blood cells is a routine practice for in-hospital trauma resuscitation. Military and civilian emergency teams are increasingly carrying prehospital blood products (PHBP) for trauma resuscitation. This study systematically reviewed the clinical literature to determine the extent to which the available evidence supports this practice. METHODS: Bibliographic databases and other sources were searched to July 2015 using keywords and index terms related to the intervention, setting, and condition. Standard systematic review methodology aimed at minimizing bias was used for study selection, data extraction, and quality assessment (protocol registration PROSPERO: CRD42014013794). Synthesis was mainly narrative with random effects model meta-analysis limited to mortality outcomes. RESULTS: No prospective comparative or randomized studies were identified. Sixteen case series and 11 comparative studies were included in the review. Seven studies included mixed populations of trauma and non-trauma patients. Twenty-five of 27 studies provided only very low quality evidence. No association between PHBP and survival was found (OR for mortality: 1.29, 95% CI: 0.84-1.96, P = 0.24). A single study showed improved survival in the first 24 h. No consistent physiological or biochemical benefit was identified, nor was there evidence of reduced in-hospital transfusion requirements. Transfusion reactions were rare, suggesting the short-term safety of PHBP administration. CONCLUSIONS: While PHBP resuscitation appears logical, the clinical literature is limited, provides only poor quality evidence, and does not demonstrate improved outcomes. No conclusions as to efficacy can be drawn. The results of randomized controlled trials are awaited. PMID- 26825636 TI - ATLS Hypovolemic Shock Classification by Prediction of Blood Loss in Rats Using Regression Models. AB - In our previous study, our input data set consisted of 78 rats, the blood loss in percent as a dependent variable, and 11 independent variables (heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse pressure, respiration rate, temperature, perfusion index, lactate concentration, shock index, and new index (lactate concentration/perfusion)). The machine learning methods for multicategory classification were applied to a rat model in acute hemorrhage to predict the four Advanced Trauma Life Support (ATLS) hypovolemic shock classes for triage in our previous study. However, multicategory classification is much more difficult and complicated than binary classification. We introduce a simple approach for classifying ATLS hypovolaemic shock class by predicting blood loss in percent using support vector regression and multivariate linear regression (MLR). We also compared the performance of the classification models using absolute and relative vital signs. The accuracies of support vector regression and MLR models with relative values by predicting blood loss in percent were 88.5% and 84.6%, respectively. These were better than the best accuracy of 80.8% of the direct multicategory classification using the support vector machine one-versus-one model in our previous study for the same validation data set. Moreover, the simple MLR models with both absolute and relative values could provide possibility of the future clinical decision support system for ATLS classification. The perfusion index and new index were more appropriate with relative changes than absolute values. PMID- 26825632 TI - pVAC-Seq: A genome-guided in silico approach to identifying tumor neoantigens. AB - Cancer immunotherapy has gained significant momentum from recent clinical successes of checkpoint blockade inhibition. Massively parallel sequence analysis suggests a connection between mutational load and response to this class of therapy. Methods to identify which tumor-specific mutant peptides (neoantigens) can elicit anti-tumor T cell immunity are needed to improve predictions of checkpoint therapy response and to identify targets for vaccines and adoptive T cell therapies. Here, we present a flexible, streamlined computational workflow for identification of personalized Variant Antigens by Cancer Sequencing (pVAC Seq) that integrates tumor mutation and expression data (DNA- and RNA-Seq). pVAC Seq is available at https://github.com/griffithlab/pVAC-Seq . PMID- 26825637 TI - Age-related changes in murine bladder structure and sensory innervation: a multiphoton microscopy quantitative analysis. AB - Our study aimed to examine and quantify age-related structural alterations in the healthy mouse bladder using ex vivo two-photon laser scanning microscopy (TPLSM). Freshly dissected bladders from 25-, 52-, and 85-week-old C57bl/6J mice were examined, and morphological analyses and quantification of cell layers and nerves were performed. The numbers of stretched, curled, branched, and total number of nerves in volume units of the stained muscle layer were quantified. We observed differences in the bladder wall architecture and innervation with age. Especially in 85-week-old mice, age-related changes were found, including detachment of urothelial cells and an increase in connective tissue, intermingled with the smooth muscle fibers in the muscle layer (collagen-smooth muscle ratio of 1.15 +/ 0.29). In 25- and 52-week-old mice, the collagen-smooth muscle ratios were 0.20 +/- 0.04 and 0.31 +/- 0.11, respectively, and a clear separation of collagen and muscle was observed. The overall number of nerves and the number of curled nerves were significantly higher in the 85-week-old mice (74.0 +/- 13.0 and 25.9 +/- 4.8, respectively), when comparing to 25-week-old mice (26.0 +/- 2.7 and 6.7 +/- 1.2, respectively) and 52-week-old mice (43.8 +/- 4.3 and 22.1 +/- 3.3, respectively). Significant age-related alterations in bladder morphology and innervation were found, when comparing freshly dissected bladder tissue from 25-, 52-, and 85-week-old mice. The higher number of curled nerves might be an indication of an increased neurotransmitter release, resulting in a higher nerve activity, with a part of the nerves being possibly mechanically impaired. This study shows that two-photon laser scanning microscopy of healthy aging male mice is a useful method to investigate and quantify the age-related changes in the bladder wall. PMID- 26825639 TI - The Cost-Effectiveness of the Integration of Nalmefene within the UK Healthcare System Treatment Pathway for Alcohol Dependence. AB - AIMS: To assess the cost-effectiveness of integrating nalmefene within the treatment pathway for alcohol dependence recommended by the National Institute for Health and Care Excellence in the UK. METHODS: A Markov model, taking a UK NHS perspective, followed a cohort with alcohol dependence and high/very high drinking risk levels (HVHDRLs), who do not require immediate detoxification and who continue at HVHDRLs after initial assessment, for 5 years. Costs and quality adjusted life years (QALYs) from treatment with nalmefene plus psychosocial support versus psychosocial support alone were modelled. The consequent incidence of alcohol-attributable harmful events and disease progression, with the possibility of requiring other options or recurrent treatment, were captured. RESULTS: Nalmefene plus psychosocial support dominated psychosocial support alone, with lower costs and increased QALYs after 5 years. Savings are driven by the higher response to nalmefene, and the subsequent lower cost accumulation for alternatives. CONCLUSIONS: Nalmefene represents a highly cost-effective treatment option in this population. The analysis shows that integrating nalmefene within the current UK clinical treatment pathway for alcohol dependence could reduce the economic burden on the NHS by limiting harmful events and disease progression. PMID- 26825641 TI - The Complexities of Interpreting Reversible Elevated Serum Creatinine Levels in Drug Development: Does a Correlation with Inhibition of Renal Transporters Exist? AB - In humans, creatinine is formed by a multistep process in liver and muscle and eliminated via the kidney by a combination of glomerular filtration and active transport. Based on current evidence, creatinine can be taken up into renal proximal tubule cells by the basolaterally localized organic cation transporter 2 (OCT2) and the organic anion transporter 2, and effluxed into the urine by the apically localized multidrug and toxin extrusion protein 1 (MATE1) and MATE2K. Drug-induced elevation of serum creatinine (SCr) and/or reduced creatinine renal clearance is routinely used as a marker for acute kidney injury. Interpretation of elevated SCr can be complex, because such increases can be reversible and explained by inhibition of renal transporters involved in active secretion of creatinine or other secondary factors, such as diet and disease state. Distinction between these possibilities is important from a drug development perspective, as increases in SCr can result in the termination of otherwise efficacious drug candidates. In this review, we discuss the challenges associated with using creatinine as a marker for kidney damage. Furthermore, to evaluate whether reversible changes in SCr can be predicted prospectively based on in vitro transporter inhibition data, an in-depth in vitro-in vivo correlation (IVIVC) analysis was conducted for 16 drugs with in-house and literature in vitro transporter inhibition data for OCT2, MATE1, and MATE2K, as well as total and unbound maximum plasma concentration (Cmax and Cmax,u) data measured in the clinic. PMID- 26825640 TI - Effect of Ondansetron on Metformin Pharmacokinetics and Response in Healthy Subjects. AB - The 5-hydroxytryptamine-3 (5-HT3) receptor antagonists such as ondansetron have been used to prevent and treat nausea and vomiting for over 2 decades. This study was to determine whether ondansetron could serve as a perpetrator drug causing transporter-mediated drug-drug interactions in humans. Twelve unrelated male healthy Chinese volunteers were enrolled into a prospective, randomized, double blind, crossover study to investigate the effects of ondansetron or placebo on the pharmacokinetics of and the response to metformin, a well-characterized substrate of organic cation transporters and multidrug and toxin extrusions (MATEs). Ondansetron treatment caused a statistically significantly higher Cmax of metformin compared with placebo (18.3 +/- 5.05 versus 15.2 +/- 3.23; P = 0.006) and apparently decreased the renal clearance of metformin by 37% as compared with placebo (P = 0.001). Interestingly, ondansetron treatment also statistically significantly improved glucose tolerance in subjects, as indicated by the smaller glucose area under the curve in the oral glucose tolerance test (10.4 +/- 1.43) as compared with placebo (11.5 +/- 2.29 mmol?mg/l) (P = 0.020). It remains possible that ondansetron itself may affect glucose homeostasis in human subjects, but our clinical study, coupled with our previous findings in cells and in animal models, indicates that ondansetron can cause a drug-drug interaction via its potent inhibition of MATE transporters in humans. PMID- 26825643 TI - A Comprehensive Review on the Predictive Performance of the Sheiner-Tozer and Derivative Equations for the Correction of Phenytoin Concentrations. AB - OBJECTIVE: In settings where free phenytoin concentrations are not available, the Sheiner-Tozer equation-Corrected total phenytoin concentration = Observed total phenytoin concentration/[(0.2 * Albumin) + 0.1]; phenytoin in ug/mL, albumin in g/dL-and its derivative equations are commonly used to correct for altered phenytoin binding to albumin. The objective of this article was to provide a comprehensive and updated review on the predictive performance of these equations in various patient populations. DATA SOURCES: A literature search of PubMed, EMBASE, and Google Scholar was conducted using combinations of the following terms: Sheiner-Tozer, Winter-Tozer, phenytoin, predictive equation, precision, bias, free fraction. STUDY SELECTION AND DATA EXTRACTION: All English-language articles up to November 2015 (excluding abstracts) were evaluated. DATA SYNTHESIS: This review shows the Sheiner-Tozer equation to be biased and imprecise in various critical care, head trauma, and general neurology patient populations. Factors contributing to bias and imprecision include the following: albumin concentration, free phenytoin assay temperature, experimental conditions (eg, timing of concentration sampling, steady-state dosing conditions), renal function, age, concomitant medications, and patient type. Although derivative equations using varying albumin coefficients have improved accuracy (without much improvement in precision) in intensive care and elderly patients, these equations still require further validation. CONCLUSIONS: Further experiments are also needed to yield derivative equations with good predictive performance in all populations as well as to validate the equations' impact on actual patient efficacy and toxicity outcomes. More complex, multivariate predictive equations may be required to capture all variables that can potentially affect phenytoin pharmacokinetics and clinical therapeutic outcomes. PMID- 26825642 TI - Age-Dependent Human Hepatic Carboxylesterase 1 (CES1) and Carboxylesterase 2 (CES2) Postnatal Ontogeny. AB - Human hepatic carboxylesterase 1 and 2 (CES1 and CES2) are important for the disposition of ester- and amide-bond-containing pharmaceuticals and environmental chemicals. CES1 and CES2 ontogeny has not been well characterized, causing difficulty in addressing concerns regarding juvenile sensitivity to adverse outcomes associated with exposure to certain substrates. To characterize postnatal human hepatic CES1 and CES2 expression, microsomal and cytosolic fractions were prepared using liver samples from subjects without liver disease (N = 165, aged 1 day to 18 years). Proteins were fractionated, detected, and quantitated by Western blotting. Median microsomal CES1 was lower among samples from subjects younger than 3 weeks (n = 36) compared with the rest of the population (n = 126; 6.27 vs. 17.5 pmol/mg microsomal protein, respectively; P < 0.001; Kruskal-Wallis test). Median cytosolic CES1 expression was lowest among samples from individuals between birth and 3 weeks of age (n = 36), markedly greater among those aged 3 weeks to 6 years (n = 90), and modestly greater still among those older than 6 years (n = 36; median values = 4.7, 15.8, and 16.6 pmol/mg cytosolic protein, respectively; P values < 0.001 and 0.05, respectively; Kruskal-Wallis test). Median microsomal CES2 expression increased across the same three age groups with median values of 1.8, 2.9, and 4.2 pmol/mg microsomal protein, respectively (P < 0.001, both). For cytosolic CES2, only the youngest age group differed from the two older groups (P < 0.001; median values = 1.29, 1.93, 2.0, respectively). These data suggest that infants younger than 3 weeks of age would exhibit significantly lower CES1- and CES2-dependent metabolic clearance compared with older individuals. PMID- 26825644 TI - A Systematic Review of Randomized Controlled Trials Comparing Hypertonic Sodium Solutions and Mannitol for Traumatic Brain Injury: Implications for Emergency Department Management. AB - OBJECTIVE: To comparatively evaluate hypertonic sodium (HTS) and mannitol in patients following acute traumatic brain injury (TBI) on the outcomes of all cause mortality, neurological disability, intracranial pressure (ICP) change from baseline, ICP treatment failure, and serious adverse events. DATA SOURCES: PubMed, EMBASE, CENTRAL, Cochrane Database of Systematic Reviews, ClinicalTrials.gov, and WHO ICTRP (World Health Organization International Clinical Trials Registry Platform) were searched (inception to November 2015) using hypertonic saline solutions, sodium chloride, mannitol, osmotic diuretic, traumatic brain injury, brain injuries, and head injury. Searches were limited to humans. Clinical practice guidelines and bibliographies were reviewed. STUDY SELECTION AND DATA EXTRACTION: Prospective, randomized trials comparing HTS and mannitol in adults (>=16 years) with severe TBI (Glasgow Coma Scale score <=8) and elevated ICP were included. ICP elevation, ICP reduction, and treatment failure were defined using study definitions. DATA SYNTHESIS: Of 326 articles screened, 7 trials enrolling a total of 191 patients met inclusion criteria. Studies were underpowered to detect a significant difference in mortality or neurological outcomes. Due to significant heterogeneity and differences in reporting ICP change from baseline, this outcome was not meta-analyzed. No difference between HTS and mannitol was observed for mean ICP reduction; however, risk of ICP treatment failure favored HTS (risk ratio [RR] = 0.39; 95% CI = 0.18 0.81). Serious adverse events were not reported. CONCLUSIONS: Based on limited data, clinically important differences in mortality, neurological outcomes, and ICP reduction were not observed between HTS or mannitol in the management of severe TBI. HTS appears to lead to fewer ICP treatment failures. PMID- 26825645 TI - Hepatitis C Treatment Exposed or Experienced? PMID- 26825646 TI - Comment: Adverse Drug Reactions in Pediatric Emergency Medicine. PMID- 26825647 TI - What does dependency on community mental health services mean? A conceptual review with a systematic search. AB - PURPOSE: Although community mental health services aim to support patients' autonomy and independence, they have repeatedly been criticised for making patients dependent. Yet, it remains often unclear what exactly is meant with dependency in this context. This review aimed to identify the meaning of the term dependency on community services in the literature. METHODS: A systematic search and conceptual review of papers where dependency is used in the context of community mental health services. Narrative synthesis was used to identify thematic concepts linked to dependency in these settings. RESULTS: Fifteen papers met the inclusion criteria. The analysis identified five different concepts of dependency on community mental health services: dislocation from the outside world; inflexibility and lack of freedom; obligation as resentment or appreciation; living with or without meaningful activities; and security. CONCLUSIONS: The findings suggest that, distinct from the exclusively negative connotation of the term dependency in a conventional medical context, dependency on community mental health services contains both negative and positive aspects. The different aspects might guide the future evaluation of the care provided in such services. PMID- 26825648 TI - Childhood antecedents of schizophrenia: Will understanding aetiopathogenesis result in schizophrenia prevention? PMID- 26825650 TI - Topical application of epidermal growth factor with no scaffold material on the healing of human traumatic tympanic membrane perforations. AB - OBJECTIVE: We evaluated the effects of conservative treatment and topical application of epidermal growth factor (EGF) with no scaffold material on the healing of human traumatic tympanic membrane perforations (TMPs). STUDY DESIGN: Prospective, randomised clinical trial. METHODS: A prospective analysis was performed between January 2015 and March 2015 for the treatment of human traumatic TMPs. The closure rate, closure time, hearing gain and rate of purulent otorrhoea were compared between the topical application of EGF and conservative treatment. RESULT: In total, 97 patients were analysed. The total closure rates did not significantly differ between the observation and EGF groups (83.0% versus 92.0%, P = 0.182). The total average closure time in the observation group was significantly longer than in the EGF group (25.1 +/- 10.5 versus 11.7 +/- 5.2 days, P = 0.001). When the closure rate was evaluated according to perforation size, no significant difference was seen for medium or large perforations (P = 0.18 and 0.21, respectively). When closure time was evaluated according to perforation size, a significant difference was seen for medium and large perforations (P = 0.001). CONCLUSIONS: This study suggests that topical application of EGF with no scaffold material may significantly shorten the closure time of human traumatic TMPs. Such a shorter recovery time may lead to reduced healthcare costs. This alternative technique to a classic myringoplasty is particularly beneficial and suitable for the closure of large human traumatic TMPs. PMID- 26825649 TI - The grapevine VviPrx31 peroxidase as a candidate gene involved in anthocyanin degradation in ripening berries under high temperature. AB - Anthocyanin levels decline in some red grape berry varieties ripened under high temperature conditions, but the underlying mechanism is not yet clear. Here we studied the effects of two different temperature regimes, representing actual Sangiovese (Vitis vinifera L.) viticulture regions, on the accumulation of mRNAs and enzymes controlling berry skin anthocyanins. Potted uniform plants of Sangiovese were kept from veraison to harvest, in two plastic greenhouses with different temperature conditions. The low temperature (LT) conditions featured average and maximum daily air temperatures of 20 and 29 degrees C, respectively, whereas the corresponding high temperature (HT) conditions were 22 and 36 degrees C, respectively. The anthocyanin concentration at harvest was much lower in HT berries than LT berries although their profile was similar under both conditions. Under HT conditions, the biosynthesis of anthocyanins was suppressed at both the transcriptional and enzymatic levels, but peroxidase activity was higher. This suggests that the low anthocyanin content of HT berries reflects the combined impact of reduced biosynthesis and increased degradation, particularly the direct role of peroxidases in anthocyanin catabolism. Overexpression of VviPrx31 decreased anthocyanin contents in Petunia hybrida petals under heat stress condition. These data suggest that high temperature can stimulate peroxidase activity thus anthocyanin degradation in ripening grape berries. PMID- 26825651 TI - Three-dimensional printing of surgical anatomy. AB - PURPOSE OF REVIEW: Over the past decade, three-dimensional printing for the medical field has been expanding rapidly throughout all of medicine. This manuscript reviews the current and potential applications for three-dimensional printing, including education, presurgical planning, surgical simulation, bioprinting, and printed surgical equipment. RECENT FINDINGS: Three-dimensional printing has proved most relevant in the fields of craniofacial, plastic, orthopedics, and especially, urologic surgery. This review focuses on several examples of how three-dimensional printing can be utilized, with emphasis on renal models for renal cell carcinoma, ureteral stents, and staghorn calculus. From an education standpoint, both patients and residents can benefit from the use of three-dimensional printed models, and even skilled surgeons report better understanding of complex procedures by using printed models. SUMMARY: Three dimensional printing in the field of medicine is growing quickly, and will soon be incorporated into the way residents are taught and patients are educated. For surgical simulation in a variety of disease processes, this will be particularly useful for urologic surgery. PMID- 26825652 TI - Molecular markers in urologic oncology: prostate cancer. AB - PURPOSE OF REVIEW: The increased clinical availability of a wide variety of molecular tests will potentially reshape the care of both men at risk for prostate cancer and men already diagnosed. It is imperative that clinicians be familiar with indications and clinical relevance of these tests. RECENT FINDINGS: The continued clinical validation in new and expanded clinical cohorts and reports of clinical experience with various molecular markers is a rapidly evolving body of literature. Results of large patient series demonstrate that these markers increase the precision of available information used in clinical management decision-making and joint physician-patient discussions regarding treatment options. SUMMARY: These tests may make more accurate management decisions possible for those whom have been 'over-diagnosed' with biologically indolent disease which represents an exceptionally small mortality risk. They also may aid in more accurate diagnosis of significant cancer, as well as more precise application of adjuvant therapy. PMID- 26825653 TI - Plasmid-like replication of a minimal Streptococcal Integrative and Conjugative Element. AB - Integrative and Conjugative Elements (ICEs) are mobile genetic elements encoding their own excision from a replicon of their bacterial host, transfer by conjugation to a recipient bacterium and re-integration for maintenance. The conjugation, recombination and regulation modules of ICEs of the ICESt3 family are grouped together in a region called the ICE "core region". Besides this core region, elements belonging to this family carry a highly variable region including cargo genes that could be involved in the bacterial adaptation or in the maintenance of the element. Although ICEs are a major class of mobile elements through bacterial genomes, the functionality of an element encoding only its excision, transfer, integration and regulation has never been experimentally demonstrated. We engineered MiniICESt3, an artificial ICE derived from ICESt3, devoid of its cargo genes and thus only harboring the core region. The functionality of this minimal element was assessed. MiniICESt3 was found to be able to excise with a 3.1% rate, transfer with a frequency of 1.0 x 10-5 transconjugants per donor cell and stably maintain by site-specific integration into the 3' end of fda gene, as ICESt3. Furthermore, MiniICESt3 was found in about ten copies per chromosome, this multicopy state likely contributing to its stability over one hundred generations even in the absence of selection. Therefore, although ICEs were primarily assumed to only replicate along with the chromosome, our results uncovered extrachromosomal rolling circle replicating plasmid-like forms of MiniICESt3. PMID- 26825654 TI - The role of Resveratrol-induced mitophagy/autophagy in peritoneal mesothelial cells inflammatory injury via NLRP3 inflammasome activation triggered by mitochondrial ROS. AB - It has been suggested that continuous exposure of peritoneal mesothelial cells (PMCs) to high glucose-containing peritoneal dialysis (PD) solutions may result in peritoneal inflammatory injury and impairment of local peritoneal host defence. Here, we investigated the effect of glucose-based PD solutions on mitochondrial reactive oxygen species (ROS) and nod-like receptor 3 (NLRP3) inflammasome activation in human PMCs (HPMCs). Exposure of HPMCs to high glucose based PD solutions resulted in ROS production, which can trigger NLRP3 activation, leading to IL-1beta secretion. Additionally, resveratrol (RSV) treatment induced mitophagy/autophagy via adenosine monophosphate-activated protein kinase (AMPK) activation. Increased mitochondrial ROS concentrations and IL-1beta upregulation were confirmed following inhibition (siRNA against Beclin1 and ATG5 or autophagy inhibitor 3MA), but not induction (RSV), of mitophagy/autophagy. Furthermore, we observed that ATG5 and Beclin1 downregulation sensitised cells to IL-1beta release induced by MSU or nigericin, which is an NLRP3 inflammasome activator. RSV treatment attenuated this effect. Taken together, this study may provide a potential therapeutic strategy for peritoneal inflammatory injury via NLRP3 inflammasome activation triggered by mitochondrial ROS. PMID- 26825655 TI - First case of corporate manslaughter against NHS trust collapses. PMID- 26825656 TI - Recurrent superficial cellulitis-like erythema associated with Helicobacter cinaedi bacteremia. PMID- 26825657 TI - Braf V600E mutation in melanoma: translational current scenario. AB - Melanoma was one of the translational cancer examples in clinic, including target therapy related to specific biomarkers impacting in the outcome of melanoma patients. Melanomagenesis involved a wide variety of mutations during his evolution; many of these mutated proteins have a kinase activity. One of the most cited proteins in melanoma is BRAF (about 50-60 % of melanomas harbors activating BRAF mutations), for these the most common is a substitution of valine to glutamic acid at codon 600 (p.V600E). Therefore, the precise identification of this underlying somatic mutation is essential; knowing the translational implications has opened a wide view of melanoma biology and therapy. PMID- 26825658 TI - In vivo expression and regulation of genes associated with vascularization during early response of sutures to tensile force. AB - Sutures are fibrous tissues that connect bones in craniofacial skeletal complexes. Cranio- and dentofacial skeletal deformities in infant and adolescent patients can be treated by applying tensile force to sutures to induce sutural bone formation. The early gene expression induced by mechanical stress is essential for bone formation in long bones; however, early gene expression during sutural bone formation induced by tensile force is poorly characterized. In vivo studies are essential to evaluate molecular responses to mechanical stresses in heterogeneous cell populations, such as sutures. In this paper we examined in vivo early gene expression and the underlying regulatory mechanism for this expression in tensile-force-applied cranial sutures, focusing on genes involved in vascularization. Tensile force upregulated expression of vascular factors, such as vascular endothelial growth factor (Vegf) and endothelial cell markers, in sutures within 3 h. The expression of connective tissue growth factor (Ctgf) and Rho-associated coiled-coil containing protein kinase 2 (Rock2) was also upregulated by tensile force. A CTGF-neutralizing antibody and the ROCK inhibitor, Y-27632, abolished tensile-force-induced Vegf expression. Moreover, tensile force activated extracellular signal-related kinase 1/2 (ERK1/2) signaling in sagittal sutures, and the ERK1/2 inhibitor, U0126, partially inhibited tensile-force-induced Ctgf expression. These results indicate that tensile force induces in vivo gene expression associated with vascularization early in tensile-force-induced sutural bone formation. Moreover, the early induction of Vegf gene expression is regulated by CTGF and ROCK2. PMID- 26825659 TI - Relationship between spinal osteoarthritis and vertebral fractures in men older than 50 years: data from the Camargo Cohort Study. AB - Spinal osteoarthritis has been suggested as a risk factor for vertebral fractures. However, results are conflicting: most of the data are focused on the lumbar region, and referred to postmenopausal women, whereas data for men are scarce. The aim of this study is to assess the relationship between spinal osteoarthritis and vertebral fractures in men over 50 years of age. We conducted a cross-sectional study, nested in a prospective population-based cohort, including 507 community-dwelling men, 93 of them with at least one vertebral fracture. Vertebral fractures, osteophytosis, and disc space narrowing (DSN) were assessed by lateral thoracic and lumbar radiographs. Anthropometric, clinical, and densitometric variables were also analyzed. A multiple logistic regression model was performed. Eighty-five percent of vertebral fractures were located at the thoracic spine. Osteophytosis and DSN showed a bimodal distribution, with major frequency peaks at mid- and distal lumbar spine. The three distributions overlapped around the T9 vertebra. We did not find any relationship between lumbar osteoarthritis and vertebral fractures. Nevertheless, thoracic osteophytosis (OR, 1.84; 95 % CI, 1.05-3.17; p = 0.03) and DSN (OR, 2.52; 95 % CI, 1.43-4.46; p = 0.001) were found to be independently associated with prevalent vertebral fractures, after adjusting for confounders. Our results suggest a positive relationship between radiologic osteoarthritic changes at the thoracic spine and prevalent vertebral fractures in men more than 50 years of age. Osteoarthritis may act as a local risk factor, in addition to other mechanical factors, resulting in a greater propensity to fracture, especially at the mid-thoracic region. PMID- 26825661 TI - Utility of the 3Di Short Version for the Diagnostic Assessment of Autism Spectrum Disorder and Compatibility with DSM-5. AB - The Developmental Diagnostic Dimensional Interview-short version (3Di-sv) provides a brief standardized parental interview for diagnosing autism spectrum disorder (ASD). This study explored its validity, and compatibility with DSM-5 ASD. 3Di-sv classifications showed good sensitivity but low specificity when compared to ADOS-2-confirmed clinical diagnosis. Confirmatory factor analyses found a better fit against a DSM-5 model than a DSM-IV-TR model of ASD. Exploration of the content validity of the 3Di-sv for the DSM-5 revealed some construct underrepresentation, therefore we obtained data from a panel of 3Di trained clinicians from ASD-specialized centers to recommend items to fill these gaps. Taken together, the 3Di-sv provides a solid basis to create a similar instrument suitable for DSM-5. Concrete recommendations are provided to improve DSM-5 compatibility. PMID- 26825660 TI - Comparison of parathyroid hormone and strontium ranelate in combination with whole-body vibration in a rat model of osteoporosis. AB - We investigated the combinatorial effects of whole-body vertical vibration (WBVV) with the primarily osteoanabolic parathyroid hormone (PTH) and the mainly antiresorptive strontium ranelate (SR) in a rat model of osteoporosis. Ovariectomies were performed on 76 three-month-old Sprague-Dawley rats (OVX, n = 76; NON-OVX, n = 12). After 8 weeks, the ovariectomized rats were divided into 6 groups. One group (OVX + PTH) received daily injections of PTH (40 ug/kg body weight/day) for 6 weeks. Another group (OVX + SR) was fed SR-supplemented chow (600 mg/kg body weight/day). Three groups (OVX + VIB, OVX + PTH + VIB, and OVX + SR + VIB) were treated with WBVV twice a day at 70 Hz for 15 min. Two groups (OVX + PTH + VIB, OVX + SR + VIB) were treated additionally with PTH and SR, respectively. The rats were killed at 14 weeks post-ovariectomy. The lumbar vertebrae and femora were removed for biomechanical and morphological assessment. PTH produced statistically significant improvements in biomechanical and structural properties, including bone mineral density (BMD) and trabecular bone quality. In contrast, SR treatment exerted mild effects, with significant effects in cortical thickness only. SR produced no significant improvement in biomechanical properties. WBVV as a single or an adjunctive therapy produced no significant improvements. In conclusion, vibration therapy administered as a single or dual treatment had no significant impact on bones affected by osteoporosis. PTH considerably improved bone quality in osteoporosis cases and is superior to treatment with SR. PMID- 26825662 TI - Do Individuals with High-Functioning Autism Who Speak a Tone Language Show Intonation Deficits? AB - This study investigated whether intonation deficits were observed in 19 Cantonese speaking adults with high-functioning autism (HFA) when compared to 19 matched neurotypical (NT) controls. This study also investigated the use of sentence final particles (SFPs) and their relationship with intonation in both groups. Standard deviations (SDs) of the fundamental frequency (F0), the total number and the type of SFPs were calculated based on narrative samples. The HFA group demonstrated significantly higher SD of F0 and a positive correlation between the type of SFPs and SD of F0. Both groups produced a similar total number and type of SFPs. The results supported the universality of atypical intonation in ASD. The relationship between intonation and SFPs could be further explored by focusing on sentences containing SFPs. PMID- 26825663 TI - Successful eradication of invasive Scopulariopsis brumptii in a liver transplant recipient. AB - Ten months after orthotopic liver transplant, a 53-year-old male patient developed cough and fever. Imaging revealed diffuse ground-glass opacities involving all lobes, and subsequent bronchoscopic washings revealed Scopulariopsis brumptii infection. The patient initially had significant clinical deterioration requiring intubation and extracorporeal membrane oxygenation. However, combination antifungal therapy, including posaconazole and terbinafine, eventually proved successful in eradicating the infection. PMID- 26825665 TI - PCV: An Alignment Free Method for Finding Homologous Nucleotide Sequences and its Application in Phylogenetic Study. AB - Online retrieval of the homologous nucleotide sequences through existing alignment techniques is a common practice against the given database of sequences. The salient point of these techniques is their dependence on local alignment techniques and scoring matrices the reliability of which is limited by computational complexity and accuracy. Toward this direction, this work offers a novel way for numerical representation of genes which can further help in dividing the data space into smaller partitions helping formation of a search tree. In this context, this paper introduces a 36-dimensional Periodicity Count Value (PCV) which is representative of a particular nucleotide sequence and created through adaptation from the concept of stochastic model of Kolekar et al. (American Institute of Physics 1298:307-312, 2010. doi: 10.1063/1.3516320 ). The PCV construct uses information on physicochemical properties of nucleotides and their positional distribution pattern within a gene. It is observed that PCV representation of gene reduces computational cost in the calculation of distances between a pair of genes while being consistent with the existing methods. The validity of PCV-based method was further tested through their use in molecular phylogeny constructs in comparison with that using existing sequence alignment methods. PMID- 26825664 TI - Do fatty acids affect fetal programming? AB - BACKGROUND: In this study discussed the primary and regulatory roles of fatty acids, and investigated the affects of fatty acids on metabolic programming. METHODS: Review of the literature was carried out on three electronic databases to assess the roles of fatty acids in metabolic programming. All abstracts and full-text articles were examined, and the most relevant articles were selected for screening and inclusion in this review. RESULTS: The mother's nutritional environment during fetal period has important effects on long term health. Fatty acids play a primary role in growth and development. Alterations in fatty acid intake in the fetal period may increase the risk of obesity and metabolic disorders in later life. Maternal fatty acid intakes during pregnancy and lactation are passed to the fetus and the newborn via the placenta and breast milk, respectively. Imbalances in fatty acid intake during the fetal period change the fatty acid composition of membrane phospholipids, which can cause structural and functional problems in cells. Additionally, the metabolic and neuroendocrine environments of the fetus and the newborn play key roles in the regulation of energy balance. CONCLUSIONS: Imbalances in fatty acid intake during pregnancy and lactation may result in permanent changes in appetite control, neuroendocrine function and energy metabolism in the fetus, leading to metabolic programming. Further studies are needed to determine the role of fatty acid intake in metabolic programming. PMID- 26825666 TI - Is there a value for probiotic supplements in gestational diabetes mellitus? A randomized clinical trial. AB - BACKGROUND: Although several studies have found probiotics encouraging in prevention of gestational diabetes mellitus (GDM), the evidence for the use of probiotics in diagnosed GDM is largely limited. The aim of this study was to assess the effect of a probiotic supplement capsule containing four bacterial strains on glucose metabolism indices and weight changes in women with newly diagnosed GDM. METHODS: Sixty-four pregnant women with GDM were enrolled into a double-blind placebo-controlled randomized clinical trial. They were randomly assigned to receive either a probiotic or placebo capsule along with dietary advice for eight consecutive weeks. The trend of weight gain along with glucose metabolism indices was assayed. RESULTS: During the first 6 weeks of the study, the weight gain trend was similar between the groups. However, in the last 2 weeks of the study, the weight gain in the probiotic group was significantly lower than in the placebo group (p < 0.05). Fasting blood sugar (FBS) decreased in both intervention (from 103.7 to 88.4 mg/dl) and control (from 100.9 to 93.6 mg/dl) groups significantly, and the decrease in the probiotic group was significantly higher than in the placebo group (p < 0.05). Insulin resistance index in the probiotic group had 6.74% reduction over the study period (p < 0.05). In the placebo group, however, there was an increase in insulin resistance index (6.45%), but the observed change in insulin resistance was not statistically significant. Insulin sensitivity index was increased in both groups. The post-intervention insulin sensitivity index in the probiotic group was not significantly different from placebo when adjusted for the baseline levels. CONCLUSIONS: The probiotic supplement appeared to affect glucose metabolism and weight gain among pregnant women with GDM. This needs to be confirmed in other settings before a therapeutic value could be approved. PMID- 26825667 TI - Cognitive Prediction of Reading, Math, and Attention: Shared and Unique Influences. AB - The current study tested a multiple-cognitive predictor model of word reading, math ability, and attention in a community-based sample of twins ages 8 to 16 years ( N = 636). The objective was to identify cognitive predictors unique to each skill domain as well as cognitive predictors shared among skills that could help explain their overlap and thus help illuminate the basis for comorbidity of related disorders (reading disability, math disability, and attention deficit hyperactivity disorder). Results indicated that processing speed contributes to the overlap between reading and attention as well as math and attention, whereas verbal comprehension contributes to the overlap between reading and math. There was no evidence that executive functioning skills help account for covariation among these skill domains. Instead, specific executive functions differentially related to certain outcomes (i.e., working memory to math and inhibition to attention). We explored whether the model varied in younger versus older children and found only minor differences. Results are interpreted within the context of the multiple deficit framework for neurodevelopmental disorders. PMID- 26825668 TI - Response to letter: Device therapy and aldosterone antagonists in the prognosis of heart failure. PMID- 26825669 TI - Impaired Perception of Sensory Consonance and Dissonance in Cochlear Implant Users. AB - HYPOTHESIS: In light of previous research demonstrating poor pitch perception in cochlear implant (CI) users, we hypothesized that the presence of consonant versus dissonant chord accompaniment in real-world musical stimuli would not impact subjective assessment of degree of pleasantness in CI users. BACKGROUND: Consonance/dissonance are perceptual features of harmony resulting from pitch relationships between simultaneously presented musical notes. Generally, consonant sounds are perceived as pleasant and dissonant ones as unpleasant. CI users exhibit impairments in pitch perception, making music listening difficult and often unenjoyable. To our knowledge, consonance/dissonance perception has not been studied in the CI population. METHODS: Twelve novel melodies were created for this study. By altering the harmonic structures of the accompanying chords, we created three permutations of varying dissonance for each melody (36 stimuli in all). Ten CI users and 12 NH listeners provided Likert scale ratings from -5 (very unpleasant) to +5 (very pleasant) for each of the stimuli. RESULTS: A two way ANOVA showed main effects for Dissonance Level and Subject Type as well as a two-way interaction between the two. Pairwise comparisons indicated that NH stimuli pleasantness ratings decreased with increasing dissonance, whereas CI ratings did not. NH pleasantness ratings were consistently lower than CI ratings. CONCLUSION: For CI users, consonant versus dissonant chord accompaniment had no significant impact on whether a melody was considered pleasant or unpleasant. This finding may be partially responsible for the decreased enjoyment of many CI users during music perception and is another manifestation of impaired pitch perception in CI users. PMID- 26825670 TI - Cochlear Implantation in a Patient With Pfeiffer Syndrome and Temporal Bone Vascular Anomalies. AB - OBJECTIVE: Pfeiffer syndrome is a rare craniosynostotic disorder resulting in premature bony fusion of the skull, which can result in abnormal temporal bone and vascular anatomy and hearing loss. Cochlear implantation in these patients requires thoughtful surgical planning given the potential for limited access to the cochlea because of subcutaneous or intratemporal vasculature. Herein, we present a patient with Pfeiffer syndrome who underwent successful cochlear implantation using preoperative Doppler ultrasound to identify large extracranial venous anatomy followed by a modified transcanal surgical approach. PATIENTS: An adult female patient with Pfeiffer syndrome. INTERVENTION(S): Preoperative axial computed tomography, catheter angiography, Doppler ultrasound, and right side cochlear implant. MAIN OUTCOME MEASURE(S): Surgical feasibility and audiometric outcomes including aided thresholds and word recognition score. RESULTS: Successful cochlear implantation was performed via a modified transcanal approach with blind sac closure of the external auditory meatus. Full electrode insertion was obtained through a round window approach. No extracranial or intratemporal vessels were encountered during surgery. CONCLUSION: Patients with significant craniosynostoses and vascular malformations of the temporal bone can undergo successful cochlear implantation. Careful preoperative planning with high resolution CT, MRA, and MRV, and/or traditional catheter angiography can assist in determining surgical feasibility and minimizing risk. We recommend preoperative Doppler ultrasound of abnormal extracranial vessels to assist in safe placement of incisions and hardware. PMID- 26825671 TI - Hearing Preservation Outcomes With a Mid-Scala Electrode in Cochlear Implantation. AB - OBJECTIVE: To evaluate hearing preservation (HP) outcomes in adult cochlear implant recipients with a mid-scala electrode. SETTING: Tertiary academic center. PATIENTS: Adult patients implanted with a mid-scala electrode between May 2013 and July 2015. INTERVENTIONS: Cochlear implantation. MAIN OUTCOME MEASURE(S): Age, sex, surgical approach, residual hearing changes post cochlear implantation, HP rates using different published classifications, and speech perception scores. RESULTS: Fifty ears for 47 patients (mean age, 58.2 yr; range, 23-86) were implanted with the electrode. Recognizing that not all patients were true HP candidates and/or underwent generally accepted HP surgical techniques, 39 ears had preoperative low-frequency hearing (audiometric threshold <= 85dB HL at 250Hz), 24 preserved acoustic hearing postoperatively (75.0%). Patients who had preserved acoustic hearing were implanted via round window (N = 18), extended round window (N = 4), or via cochleostomy (N = 2) approaches. Mean threshold elevation for low-frequency pure-tone average (125, 250, and 500 Hz) was 20.2 dB after surgery. 43.8% of patients had aidable low-frequency hearing at activation, 30.0% at 6-months postoperatively, and 30.8% 1-year postopera tively. Using a formula outlined by Skarzynski and colleagues, at 6-months postoperatively, 15.0% of patients had complete HP, whereas 40.0% had partial HP. At 1-year, these percentages decreased to 0% and 38.5%, respectively. Age, type of approach, and perioperative steroid use were not correlated with HP outcomes at activation and 6-months postoperatively (p > 0.05). CONCLUSION: The mid-scala electrode evaluated allows preservation of low-frequency hearing in patients undergoing cochlear implantation at rates and degrees of preservation close to other reports in the cochlear implant literature. PMID- 26825672 TI - A Comparative Review of Osseointegration Failure Between Osseointegrated Bone Conduction Device Models in Pediatric Patients. AB - OBJECTIVE: Compare rates of osseointegration failure (OIF) between system 2 (200 series) and system 3 (BI300) osseointegrated bone conduction device (OCBD) models. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center. PATIENTS: Pediatric patients who were implanted with either system 2 or system 3 OCBD between May 2009 and July 2014 at Arkansas Children's Hospital. INTERVENTIONS: Implantation with either system 2 or system 3 OCBD using 3- and 4 mm implants with 5.5- and 8.5-mm abutments (system 2) or 6- and 9-mm abutments (system 3). MAIN OUTCOME MEASURES: OIF with resulting loss of flange-fixture. RESULTS: OIF occurred in 28.6% (14/49) of implanted fixtures in system 2 compared with 8.0% (2/25) of implanted fixtures in system 3 (p = 0.042). The average time to complication for system 2 was 13 months compared with 3 months for system 3. The causes of OIF in system 2 were trauma (n = 4), chronic soft tissue disease (n = 5), or idiopathic in nature (n = 5). System 3 failures were both because of trauma. Using the combined cohorts, the average age of patients who experienced OIF was 8.7 years, compared with 11.4 years in patients without OIF (p = 0.047). There was no difference in OIF among 3-mm and 4-mm screws (p = 0.876), linear and flap technique (p = 0.375), or surgeons (p = 0.211). CONCLUSION: System 3 OCBD showed a significantly reduced rate of OIF compared with system 2 in our study. Modification to the system 2 implant resulted in improved rate of OIF. Younger age was independently associated with a higher rate of OIF when evaluating both systems. PMID- 26825673 TI - CacyBP/SIP inhibits Doxourbicin-induced apoptosis of glioma cells due to activation of ERK1/2. AB - Calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP) was previously reported to promote the proliferation of glioma cells. However, the effect of CacyBP/SIP on apoptosis of glioma is poorly understood. Here, our study shows that CacyBP/SIP plays a role in inhibiting doxorubicin (DOX) induced apoptosis of glioma cells U251 and U87. Overexpression of CacyBP/SIP obviously suppressed the DOX-induced cell apoptosis. On the contrary, silencing of CacyBP/SIP significantly promoted it. Further investigation indicated that inhibition of apoptosis by CacyBP/SIP was relevant to its nuclear translocation in response to the DOX treatment. Importantly, we found that the level of p ERK1/2 in nuclei was related to the nuclear accumulation of CacyBP/SIP. Finally, the role of CacyBP/SIP was confirmed in vivo in a mouse model with the cell line stably silencing CacyBP/SIP. Taken together, our results suggest that CacyBP/SIP plays an important role in inhibiting apoptosis of glioma cells which might be mediated by ERK1/2 signaling pathway, which will provide some guidance for the treatment of glioma. PMID- 26825674 TI - T Follicular Helper Cell Plasticity Shapes Pathogenic T Helper 2 Cell-Mediated Immunity to Inhaled House Dust Mite. AB - Exposure to environmental antigens, such as house dust mite (HDM), often leads to T helper 2 (Th2) cell-driven allergic responses. However, the mechanisms underlying the development of these responses are incompletely understood. We found that the initial exposure to HDM did not lead to Th2 cell development but instead promoted the formation of interleukin-4 (IL-4)-committed T follicular helper (Tfh) cells. Following challenge exposure to HDM, Tfh cells differentiated into IL-4 and IL-13 double-producing Th2 cells that accumulated in the lung and recruited eosinophils. B cells were required to expand IL-4-committed Tfh cells during the sensitization phase, but did not directly contribute to disease. Impairment of Tfh cell responses during the sensitization phase or Tfh cell depletion prevented Th2 cell-mediated responses following challenge. Thus, our data demonstrate that Tfh cells are precursors of HDM-specific Th2 cells and reveal an unexpected role of B cells and Tfh cells in the pathogenesis of allergic asthma. PMID- 26825675 TI - Non-exophytic Lambl excrescences of aortic valves: a morphological study. AB - AIMS: To elucidate the histopathological findings of classical Lambl excrescences (LEs) and non-exophytic LEs (non-ex LEs) without excrescent papillary features. METHODS AND RESULTS: We examined 126 aortic valves (AVs) and revealed LEs (non-ex and/or classical), non-ex LEs and classical LEs in 106, 78 and 88 AVs, respectively. The detection of non-ex LEs was challenging, but elastica van Gieson stain highlighted their presence. Non-ex and classical LEs chiefly involved the ventricular regions, favoured posterior cusps and coexisted in the same areas of 31 AVs. A possible transformation of classical LEs into non-ex LEs was suggested histologically in 39 AVs. Non-ex LEs were associated with age of >70 years (P < 0.001) and marked deformity (P = 0.007). Classical LEs were associated inversely with marked deformity (P < 0.001), but not with age of >70 years. Compared with age- and sex-matched control AVs, non-ex LEs and marked deformity in dysfunctional AVs were more common (P = 0.037 and P < 0.001, respectively), but classical LEs were less common (P = 0.021). CONCLUSIONS: Non ex LEs have subtle features but are a common form of LEs, and seem to develop from classical LEs. AV dysfunction-related marked deformity can promote non-ex LEs. PMID- 26825676 TI - The validity of birth and pregnancy histories in rural Bangladesh. AB - BACKGROUND: Maternity histories provide a means of estimating fertility and mortality from surveys. METHODS: The present analysis compares two types of maternity histories-birth histories and pregnancy histories-in three respects: (1) completeness of live birth and infant death reporting; (2) accuracy of the time placement of live births and infant deaths; and (3) the degree to which reported versus actual total fertility measures differ. The analysis covers a 15 year time span and is based on two data sources from Matlab, Bangladesh: the 1994 Matlab Demographic and Health Survey and, as gold standard, the vital events data from Matlab's Demographic Surveillance System. RESULTS: Both histories are near perfect in live-birth completeness; however, pregnancy histories do better in the completeness and time accuracy of deaths during the first year of life. CONCLUSIONS: Birth or pregnancy histories can be used for fertility estimation, but pregnancy histories are advised for estimating infant mortality. PMID- 26825677 TI - Definition of nocturnal gastroesophageal reflux for studies on respiratory diseases. AB - OBJECTIVE: Nocturnal gastroesophageal reflux (nGER) has been associated with respiratory diseases. Our aim was to study a questionnaire method to identify nGER subjects with respiratory involvement in a general population. MATERIAL AND METHODS: A subgroup of Icelandic participants in the European Community Respiratory Health Survey III (ECRHS III) reporting symptoms of nGER (n = 48) as well as age and gender paired controls (n = 42) were studied further by a structured interview, questionnaires, laryngeal fibrescopy, and exhaled breath condensate. A subgroup underwent 24-h oesophageal pH impedance (24-h MII-pH) measurements. Symptoms of nGER were assessed with a modified version of the reflux disease questionnaire (RDQ), where symptoms were divided into daytime and nocturnal. A report of nGER both at baseline and at follow-up was defined as persistent nGER. RESULTS: Participants reporting persistent nGER had significantly more signs of laryngopharyngeal reflux according to the reflux finding score than those without nGER (Mean +/- SD: 5.1 +/- 2.3 vs. 3.9 +/- 2.2, p = 0.02). Of the 16 persistent nGER subjects that underwent 24-h MII-pH, 11 had abnormal gastroesophageal reflux, but none of three control subjects (69% vs. 0%). Pepsin was more commonly found in exhaled breath condensate in the nGER group (67% vs. 45%, p = 0.04). CONCLUSIONS: Participants with nGER symptoms at least once a month, reported on two occasions, had a high level of positive 24-h MII-pH measurements, laryngeal inflammation and pepsin in exhaled breath condensate. This nGER definition identified a representable group for studies on nGER and respiratory diseases in a general population. PMID- 26825678 TI - First description of 'Chalky back' phenomenon in banana prawns (Fenneropenaeus merguiensis) and its possible association with Vibrio and Photobacterium species. AB - Here we report a newly identified 'Chalky back' phenomenon in banana prawns (Fenneropenaeus merguiensis) farmed in North Queensland, Australia. This was characterized by localized white discoloured segmentation of the cervical groove, moreover, after cooking the prawns exploded, making them unfit for commercial sale. Histological examination revealed breakdown of gut and abdominal muscle tissue in some moribund specimens. We selectively isolated Vibrio spp., which are known prawn pathogens, from healthy and Chalky back specimens. Isolated bacteria were identified, typed and tested for the presence of eight virulence genes (VGs), biofilm formation, adherence and cytotoxicity to fish cells. In all, 32 isolates were recovered and identified as Vibrio harveyi, V. owensii, V. sinaloensis-like, V. campbellii, V. shilonii, Vibrio sp. and Photobacterium damselae using 16S rRNA gene sequencing. All V. harveyi carried VGs coding for haemolysin, toxR and flagella; formed biofilm; and adhered to both cell lines. This was similar to the V. sinaloensis-like strains that were only isolated from Chalky back specimens. Our data suggest that Vibrio spp. may play a role in the pathogenesis of Chalky back. This study is the first report of Chalky back phenomenon in farmed banana prawns that needs to be closely monitored by the industry. PMID- 26825679 TI - The role of temperate bacteriophages in bacterial infection. AB - Bacteriophages are viruses that infect bacteria. There are an estimated 10(31) phage on the planet, making them the most abundant form of life. We are rapidly approaching the centenary of their identification, and yet still have only a limited understanding of their role in the ecology and evolution of bacterial populations. Temperate prophage carriage is often associated with increased bacterial virulence. The rise in use of technologies, such as genome sequencing and transcriptomics, has highlighted more subtle ways in which prophages contribute to pathogenicity. This review discusses the current knowledge of the multifaceted effects that phage can exert on their hosts and how this may contribute to bacterial adaptation during infection. PMID- 26825680 TI - Regulation of matrix metalloproteinase-1 and alpha-smooth muscle actin expression by interleukin-1 alpha and tumour necrosis factor alpha in hepatic stellate cells. AB - Hepatic stellate cells (HSCs) are key players in liver fibrosis and regeneration via collagen degradation and synthesis. These phenomena involve inflammatory cytokines released from non-parenchymal liver cells such as Kupffer cells. Although the effects of individual cytokines on many cell types have been investigated in various conditions, such as inflammation and tissue fibrosis, investigating the effect of combined cytokines would further our understanding of the regulatory mechanisms in tissue fibrosis. Here, we report the effect of multiple cytokine combinations on primary HSCs. We first examined the effect of individual cytokines and then the simultaneous exposure of different cytokines, including interleukin-6 (IL-6), IL-1 alpha (IL-1alpha), platelet-derived growth factor (PDGF), tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), on matrix metalloproteinase-1 (MMP1) gene expression in primary HSCs. We observed that the combination of all five cytokines induced higher levels of MMP1 gene expression. Of these cytokines, TNF-alpha and IL 1alpha were found to be the key cytokines for not only inducing MMP1 expression, but also increasing alpha-smooth muscle actin gene expression. In conclusion, the combined treatment of TNF-alpha and IL-1alpha on HSCs had an enhanced effect on the expression of the fibrotic genes, MMP1 and alpha-smooth muscle actin, so appears to be an important regulator for tissue regeneration. This finding suggests that stimulation with combined anti-fibrotic cytokines is a potential approach in the development of a novel therapy for the recovery of liver fibrosis. PMID- 26825681 TI - Epithelial cells from oral mucosa: How to cultivate them? AB - Epithelial cells from oral mucosa (EOM) are responsible for important functions, like the primary protection of oral mucosa against external aggressions building a mechanical barrier against microorganisms, mechanical damage, toxic material, thermal regulation and secretion of different classes of inflammatory mediators. EOM could be an interesting tool for cellular and molecular biology research. Usually, EOM are collected by a painful and invasive process. In this study, we propose an alternative method to cultivate EOM collected by non-invasive scraping method of oral mucosa. Papanicolaou staining showed mainly two kinds of epithelial cell population after EOM scraping. As result of the five culture methods tested here, our results revealed that the EOM were successfully cultured on a murine feeder layer. In addition, EOM could be frozen and thawed, without morphology changes and loss of viability. Our findings suggest that EOM can be considered as a good cell source for many purposes, such as genetic studies, diagnosis and cell therapy. PMID- 26825682 TI - Biomechanical and biochemical characterization of porcine tracheal cartilage. AB - OBJECTIVES/HYPOTHESIS: The trachea is essential to respiratory function and is a mechanically and biochemically complex composite tissue. Tissue-engineering approaches to treat tracheal diseases require detailed knowledge of the native mechanical and biochemical properties of the trachea. Although the porcine trachea represents an excellent preclinical model, relevant mechanical and biochemical composition are incompletely characterized. STUDY DESIGN: Experimental. The mechanical and biochemical properties of 12 intact porcine tracheas were determined to characterize their compliance, as well as the aggregate modulus, bidirectional elastic modulus, hydraulic permeability, and biochemical characteristics of individual cartilage rings. RESULTS: Data demonstrate the glycosaminoglycan content of tracheal rings was (mean +/- standard deviation) 190 +/- 49 MUg/mg. Hydroxyproline content was 8.2 +/- 3.2 MUg/mg, and DNA content was 1.3 +/- 0.27 MUg/mg, a four-fold difference between circumferential elastic modulus (5.6 +/- 2.0 megapascal [MPa]) and longitudinal composite elastic modulus (1.1 +/- 0.7 MPa, P < 0.0001) was also observed. Aggregate modulus (stiffness) of porcine tracheal rings was 1.30 +/- 0.28 MPa, and inflationary compliance was 0.00472 +/- 0.00188 cmH2 O(-1) . CONCLUSION: This study presents a comprehensive characterization of the relevant biochemical and mechanical properties of porcine tracheal cartilage, which is considered an excellent candidate for xenogenic tracheal graft and a source for tissue engineered tracheal reconstruction. The range of parameters characterized in this study agrees with those reported for hyaline cartilage of the airway in other species. These characteristics can be used as quantitative benchmarks for tissue engineering approaches to treat tracheal disease. LEVEL OF EVIDENCE: NA. Laryngoscope, 126:E325-E331, 2016. PMID- 26825683 TI - Patient-Reported Outcomes of Elderly Adults with Chronic Hepatitis C Treated with Interferon- and Ribavirin-Free Regimens. AB - The purpose of the study was to assess the effect of different treatment regimens for chronic hepatitis C on patient-reported outcomes (PROs) of individuals aged 65 and older with chronic hepatitis C. PRO data from eight multinational multicenter Phase 2 and 3 clinical trials were included. Of 3,120 participants in these clinical trials, 229 were aged 65 and older (67.8 +/- 3.2, 57% male, 75% treatment-naive, 22% cirrhotic), and 90 of those received ledipasvir plus sofosbuvir (LDV + SOF), 119 received SOF plus ribavirin (SOF + RBV), and 20 received pegylated IFN, SOF, and RBV (IFN + SOF + RBV). Participants aged 65 and older had slightly more pretreatment PRO impairment in their physical functioning than younger individuals (-3.1% on a normalized 0-100% PRO scale, P < .001). Despite this, these participants experienced significant PRO improvement during treatment with IFN-free RBV-free regimens (up to +8.0%, P < .001), similar to improvements in younger participants. In contrast, participants aged 65 and older experienced substantial decline in PROs while receiving IFN- or RBV-containing regimens (up to -18.9% in IFN + SOF + RBV, -10.4% in IFN-free SOF+RBV, P < .001), and some were greater than in the younger group. Nevertheless, after achieving sustained viral clearance at Posttreatment Week 12, PROs in participants aged 65 and older improved regardless of the regimen (up to +10.4%, P < .001). In multivariate analysis of the cohort aged 65 and older, the use of IFN and RBV was consistently associated with PRO impairment during treatment. The use of an IFN- and RBV-free anti-HCV regimen in older adults with hepatitis C results in significant improvement of PROs. PMID- 26825685 TI - Differences in Nutrient Intake and Biochemical Nutrient Status Between Sarcopenic and Nonsarcopenic Older Adults-Results From the Maastricht Sarcopenia Study. AB - BACKGROUND: There is growing evidence of a relationship between nutrients and muscle mass, strength, and physical performance. Although nutrition is seen as an important pillar of treating sarcopenia, data on the nutritional intake of sarcopenic older adults are limited. OBJECTIVE: To investigate potential nutritional gaps in the sarcopenic population, the present study compared nutrient intake and biochemical nutrient status between sarcopenic and nonsarcopenic older adults. DESIGN: The Maastricht Sarcopenia Study included 227 community-dwelling older adults (>=65 years) from Maastricht, 53 of whom were sarcopenic based on the European Working Group on Sarcopenia in Older People algorithm. Habitual dietary intake was assessed with a food frequency questionnaire and data on dietary supplement use were collected. In addition, serum 25-hydroxyvitamin D, magnesium and alpha-tocopherol/cholesterol, plasma homocysteine and red blood cell n-3, and n-6 fatty acids profiles were assessed. Nutrient intake and biochemical nutrient status of the sarcopenic groups were compared with those of the nonsarcopenic groups. The robustness of these results was tested with a multiple regression analysis, taking into account between-group differences in characteristics. RESULTS: Sarcopenic older adults had a 10%-18% lower intake of 5 nutrients (n-3 fatty acids, vitamin B6, folic acid, vitamin E, magnesium) compared with nonsarcopenic older adults (P < .05). When taking into account dietary supplement intake, a 19% difference remained for n-3 fatty acids intake (P = .005). For the 2 biochemical status markers, linoleic acid and homocysteine, a 7% and 27% difference was observed, respectively (P < .05). The higher homocysteine level confirmed the observed lower vitamin B intake in the sarcopenic group. Observed differences in eicosapentaenoic acid and 25 hydroxyvitamin D between the groups were related to differences in age and living situation. CONCLUSIONS: Sarcopenic older adults differed in certain nutritional intakes and biochemical nutrient status compared with nonsarcopenic older adults. Dietary supplement intake reduced the gap for some of these nutrients. Targeted nutritional intervention may therefore improve the nutritional intake and biochemical status of sarcopenic older adults. PMID- 26825684 TI - Walking-Induced Fatigue Leads to Increased Falls Risk in Older Adults. AB - BACKGROUND: For older adults, falls are a serious health problem, with more than 30% of people older than 65 suffering a fall at least once a year. One element often overlooked in the assessment of falls is whether a person's balance, walking ability, and overall falls risk is affected by performing activities of daily living such as walking. OBJECTIVE: This study assessed the immediate impact of incline walking at a moderate pace on falls risk, leg strength, reaction time, gait, and balance in 75 healthy adults from 30 to 79 years of age. Subjects were subdivided into 5 equal groups based on their age (group 1, 30-39 years; group 2, 40-49 years; group 3, 50-59 years; group 4, 60-69 years; group 5, 70-79 years). METHODS: Each person's falls risk (using the Physiological Profile Assessment), simple reaction time, leg strength, walking ability, and standing balance were assessed before and after a period of incline walking on an automated treadmill. The walking task consisted of three 5-minute trials at a faster than preferred pace. Fatigue during walking was elicited by increasing the treadmill incline in increments of 2 degrees (from level) every minute to a maximum of 8 degrees . RESULTS: As predicted, significant age-related differences were observed before the walking activity. In general, increasing age was associated with declines in gait speed, lower limb strength, slower reaction times, and increases in overall falls risk. Following the treadmill task, older adults exhibited increased sway (path length 60-69 years; 10.2 +/- 0.7 to 12.1 +/- 0.7 cm: 70-79 years; 12.8 +/- 1.1 to 15.1 +/- 0.8 cm), slower reaction times (70-79 years; 256 +/- 6 to 287 +/- 8 ms), and declines in lower limb strength (60-69 years; 36 +/- 2 to 31 +/- 1 kg: 70-79 years; 32.3 +/- 2 to 27 +/- 1 kg). However, a significant increase in overall falls risk (pre; 0.51 +/- 0.17: post; 1.01 +/- 0.18) was only seen in the oldest group (70-79 years). For all other persons (30-69 years), changes resulting from the treadmill-walking task did not lead to a significant increase in falls risk. CONCLUSIONS: As most falls occur when an individual is moving and/or fatigued, assessing functional properties related to balance, gait, strength, and falls risk in older adults both at rest and following activity may provide additional insight. PMID- 26825687 TI - Membrane contact sites between pathogen-containing compartments and host organelles. AB - Intracellular pathogens survive and replicate within specialised membrane-bound compartments that can be considered as pseudo-organelles. Using the obligate intracellular bacterium Chlamydia as an illustrative example, we consider the modes of lipid transport between pathogen-containing compartments and host organelles, including the formation of static membrane contact sites. We discuss how lipid scavenging can be mediated via the reprogramming of cellular transporters at these interfaces and describe recent data suggesting that pathogen effectors modulate the formation of specific membrane contacts. Further study of these emerging mechanisms is likely to yield new insights into the cell biology of lipid transport and organelle communication, which highlights potential new targets and strategies for future therapeutics. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID- 26825688 TI - The evolution of ERMIONE in mitochondrial biogenesis and lipid homeostasis: An evolutionary view from comparative cell biology. AB - The ER-mitochondria organizing network (ERMIONE) in Saccharomyces cerevisiae is involved in maintaining mitochondrial morphology and lipid homeostasis. ERMES and MICOS are two scaffolding complexes of ERMIONE that contribute to these processes. ERMES is ancient but has been lost in several lineages including animals, plants, and SAR (stramenopiles, alveolates and rhizaria). On the other hand, MICOS is ancient and has remained present in all organisms bearing mitochondrial cristae. The ERMIONE precursor evolved in the alpha-proteobacterial ancestor of mitochondria which had the central subunit of MICOS, Mic60. The subsequent evolution of ERMIONE and its interactors in eukaryotes reflects the integrative co-evolution of mitochondria and their hosts and the adaptive paths that some lineages have followed in their specialization to certain environments. By approaching the ERMIONE from a perspective of comparative evolutionary cell biology, we hope to shed light on not only its evolutionary history, but also how ERMIONE components may function in organisms other than S. cerevisiae. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID- 26825686 TI - MicroRNAs as regulators of endothelial cell functions in cardiometabolic diseases. AB - Endothelial cells (ECs) provide nutrients and oxygen essential for tissue homeostasis. Metabolic imbalances and other environmental stimuli, like cytokines or low shear stress, trigger endothelial inflammation, increase permeability, compromise vascular tone, promote cell proliferation, and ultimately cause cell death. These factors contribute to EC dysfunction, which is crucial in the development of cardiometabolic diseases. microRNAs (miRNAs) are small non-coding RNAs that have important functions in the regulation of ECs. In the present review, we discuss the role of miRNAs in various aspects of EC pathology in cardiometabolic diseases like atherosclerosis, type 2 diabetes, obesity, and the metabolic syndrome, and in complication of those pathologies, like ischemia. We also discuss the potential therapeutic applications of miRNAs in promoting angiogenesis and neovascularization in tissues where the endothelium is damaged in different cardiometabolic diseases. This article is part of a Special Issue entitled: MicroRNAs and lipid/energy metabolism and related diseases edited by Carlos Fernandez-Hernando and Yajaira Suarez. PMID- 26825689 TI - Biochemical characterization of the tomato phosphatidylinositol-specific phospholipase C (PI-PLC) family and its role in plant immunity. AB - Plants possess effective mechanisms to quickly respond to biotic and abiotic stresses. The rapid activation of phosphatidylinositol-specific phospholipase C (PLC) enzymes occurs early after the stimulation of plant immune-receptors. Genomes of different plant species encode multiple PLC homologs belonging to one class, PLCzeta. Here we determined whether all tomato homologs encode active enzymes and whether they can generate signals that are distinct from one another. We searched the recently completed tomato (Solanum lycopersicum) genome sequence and identified a total of seven PLCs. Recombinant proteins were produced for all tomato PLCs, except for SlPLC7. The purified proteins showed typical PLC activity, as different PLC substrates were hydrolysed to produce diacylglycerol. We studied SlPLC2, SlPLC4 and SlPLC5 enzymes in more detail and observed distinct requirements for Ca(2+) ions and pH, for both their optimum activity and substrate preference. This indicates that each enzyme could be differentially and specifically regulated in vivo, leading to the generation of PLC homolog-specific signals in response to different stimuli. PLC overexpression and specific inhibition of PLC activity revealed that PLC is required for both specific effector- and more general "pattern"-triggered immunity. For the latter, we found that both the flagellin-triggered response and the internalization of the corresponding receptor, Flagellin Sensing 2 (FLS2) of Arabidopsis thaliana, are suppressed by inhibition of PLC activity. Altogether, our data support an important role for PLC enzymes in plant defence signalling downstream of immune receptors. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. PMID- 26825690 TI - Characterization of a mutant form of human apolipoprotein B (Thr26_Tyr27del) associated with familial hypobetalipoproteinemia. AB - We have previously identified a deletion mutant of human apoB [apoB (Thr26_Tyr27del)] in a subject with primary hypobetalipoproteinemia. The present study determined the effect of Thr26_Tyr27del mutation on apoB secretion using transfected McA-RH7777 cells. Transient or stable transfection of apoB-48 containing the Thr26_Tyr27del mutation showed drastically reduced secretion of the mutant as compared to wild-type apoB-48. No lipoproteins containing the mutant apoB-48 were secreted into the medium. Incubation of transfected cells in a lipid-rich medium in the presence of cycloheximide showed rapid turnover of cell-associated mutant apoB-48 as compared to that of wild-type apoB-48. Immunofluorescence experiments showed that the mutant apoB-48 was mostly localized in the endoplasmic reticulum. Treatment with the proteasomal inhibitor MG132 markedly attenuated the turnover of cell-associated mutant apoB-48, whereas treatment with inhibitors of autophagosomal/lysosomal function (e.g. 3-MA or ammonium chloride) had no effect. Taken together, these results indicated that the defective secretion of the Thr26_Tyr27del mutant was associated with increased intracellular degradation of apoB through the proteasome-dependent pathway. PMID- 26825691 TI - Lipoprotein carriers of microRNAs. AB - Lipoproteins, namely high-density lipoproteins (HDL), transport a wide-variety of cargo in addition to cholesterol and lipids. In 2011, HDL and low-density lipoproteins (LDL) were reported to transport microRNAs (miRNA). Since the original discovery, there has been great excitement for this topic and a handful of follow-up publications. Here, we review the current landscape of lipoprotein transport of miRNAs. HDL-miRNAs have been demonstrated to be altered in cardiovascular disease (CVD), including hypercholesterolemia and atherosclerosis. As such, HDL- and LDL-miRNAs may represent a novel class of disease biomarkers. Below, we review HDL-miR-92a and miR-486 levels in myocardial infarction and unstable angina, and HDL-miR-223 and miR-24 levels in coronary artery disease (CAD). Moreover, we address HDL's contribution to the total pool of extracellular miRNAs in plasma and differential distribution of miRNAs across HDL subspecies. Finally, we address current and future challenges for this new field and the barriers to such work. This article is part of a Special Issue entitled: MicroRNAs and lipid/energy metabolism and related diseases edited by Carlos Fernandez-Hernando and Yajaira Suarez. PMID- 26825692 TI - PPARbeta/delta and lipid metabolism in the heart. AB - Cardiac lipid metabolism is the focus of attention due to its involvement in the development of cardiac disorders. Both a reduction and an increase in fatty acid utilization make the heart more prone to the development of lipotoxic cardiac dysfunction. The ligand-activated transcription factor peroxisome proliferator activated receptor (PPAR)beta/delta modulates different aspects of cardiac fatty acid metabolism, and targeting this nuclear receptor can improve heart diseases caused by altered fatty acid metabolism. In addition, PPARbeta/delta regulates glucose metabolism, the cardiac levels of endogenous antioxidants, mitochondrial biogenesis, cardiomyocyte apoptosis, the insulin signaling pathway and lipid induced myocardial inflammatory responses. As a result, PPARbeta/delta ligands can improve cardiac function and ameliorate the pathological progression of cardiac hypertrophy, heart failure, cardiac oxidative damage, ischemia reperfusion injury, lipotoxic cardiac dysfunction and lipid-induced cardiac inflammation. Most of these findings have been observed in preclinical studies and it remains to be established to what extent these intriguing observations can be translated into clinical practice. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID- 26825693 TI - The TULIP superfamily of eukaryotic lipid-binding proteins as a mediator of lipid sensing and transport. AB - The tubular lipid-binding (TULIP) superfamily has emerged in recent years as a major mediator of lipid sensing and transport in eukaryotes. It currently encompasses three protein families, SMP-like, BPI-like, and Takeout-like, which share a common fold. This fold consists of a long helix wrapped in a highly curved anti-parallel beta-sheet, enclosing a central, lipophilic cavity. The SMP like proteins, which include subunits of the ERMES complex and the extended synaptotagmins (E-Syts), appear to be mainly located at membrane contacts sites (MCSs) between organelles, mediating inter-organelle lipid exchange. The BPI-like proteins, which include the bactericidal/permeability-increasing protein (BPI), the LPS (lipopolysaccharide)-binding protein (LBP), the cholesteryl ester transfer protein (CETP), and the phospholipid transfer protein (PLTP), are either involved in innate immunity against bacteria through their ability to sense lipopolysaccharides, as is the case for BPI and LBP, or in lipid exchange between lipoprotein particles, as is the case for CETP and PLTP. The Takeout-like proteins, which are comprised of insect juvenile hormone-binding proteins and arthropod allergens, transport, where known, lipid hormones to target tissues during insect development. In all cases, the activity of these proteins is underpinned by their ability to bind large, hydrophobic ligands in their central cavity and segregate them away from the aqueous environment. Furthermore, where they are involved in lipid exchange, recent structural studies have highlighted their ability to establish lipophilic, tubular channels, either between organelles in the case of SMP domains or between lipoprotein particles in the case of CETP. Here, we review the current knowledge on the structure, versatile functions, and evolution of the TULIP superfamily. We propose a deep evolutionary split in this superfamily, predating the Last Eukaryotic Common Ancestor, between the SMP-like proteins, which act on lipids endogenous to the cell, and the BPI like proteins (including the Takeout-like proteins of arthropods), which act on exogenous lipids. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID- 26825695 TI - Are we curing more older adults with acute myeloid leukemia with allogeneic transplantation in CR1? AB - PURPOSE OF REVIEW: Despite the fact that acute myeloid leukemia (AML) is most common in older adults aged at least 60 years, curative therapy remains elusive in this population. Here we examine the data for predicting which patients are candidates for 'curative therapy', available therapeutic options, and the utilization of reduced intensity allogeneic stem cell transplantation in first remission. RECENT FINDINGS: Incorporation of geriatric assessment tools to assess patient frailty, in addition to evaluation of comorbid conditions, improves patient selection for intense therapy. The majority of patients eligible for and treated with induction chemotherapy achieve complete remission, and overall survival in the older AML population is superior after allogeneic stem cell transplant. However, population-based studies continue to demonstrate the undertreatment or lack of treatment of older AML patients. SUMMARY: New patient assessment tools, ability to offer more successful outcomes after induction chemotherapy, and improved survival after allogeneic transplantation has not yet translated to increased 'curative' treatment on a population level of older AML patients. It is critical that the tools and therapies available be put into practice while older patient enrollment in well designed therapeutic clinical trials which include the option of allogeneic transplantation is increased. PMID- 26825694 TI - Novel therapeutic strategies in myelodysplastic syndromes: do molecular genetics help? AB - PURPOSE OF REVIEW: Many studies over the past decade have together identified genes that are recurrently mutated in the myelodysplastic syndromes (MDS). We will summarize how this information has informed our understanding of disease pathogenesis and behavior, with an emphasis on how this information may inform therapeutic strategies. RECENT FINDINGS: Genomic sequencing techniques have allowed for the identification of many recurrently mutated genes in MDS, with the most common mutations being found in epigenetic modifiers and components of the splicing machinery. Although many mutations are associated with clinical outcomes and disease phenotypes, at the current time they add relatively little to already robust clinical prognostic algorithms. However, as molecular genetic data are accumulated in larger numbers of patients, it is likely that the clinical significance of co-occurring mutations and less common mutations will come to light. Finally, mutated genes may identify biologically distinct subgroups of MDS that may benefit from novel therapies, and a subset of these genes may themselves serve as therapeutic targets. SUMMARY: Advances in our knowledge of the molecular genetics of MDS have significantly improved our understanding of disease biology and promise to improve tools for clinical decision-making and identify new therapies for patients. PMID- 26825696 TI - New molecular genetics in the diagnosis and treatment of myeloproliferative neoplasms. AB - PURPOSE OF REVIEW: Myeloproliferative neoplasms (MPN) are conditions of great interest because of the identification of their molecular basis and of the entering of new small molecules into clinical practice. The aim of this review is to report the role of mutations in the diagnosis, prognosis, and in the prediction of response to JAK inhibitors in MPN. RECENT FINDINGS: New mutations of the CALR gene have been discovered in patients without JAK2 or MPL mutations and are now included in the World Health Organization classification system. The role of ASXL1 and SRSF2 together with the driver mutations is emerging in the prognostication of myelofibrosis. SUMMARY: A wide mutational analysis of MPN helps to define diagnosis and prognosis. In the future, clinical trials based on a robust valuation of mutations will guide treatment decision-making towards precision medicine. PMID- 26825697 TI - Should autotransplantation in acute myeloid leukemia in first complete remission be revisited? AB - PURPOSE OF REVIEW: Despite numerous studies, the best postremission therapy in acute myeloid leukemia (AML) is a subject of intense controversy. Major prognostic factors for disease outcome are the genetic alterations of AML, patient's age, and performance status. AML is more common in older adults, with a median age of 72 years. However, in this age group the unfavorable cytogenetics dominates at a time when biologically it may be most difficult to administer optimal intensive therapy. RECENT FINDINGS: Autologous stem cell transplantation (ASCT) enables the administration of high-dose therapy supported by stem cell infusion with a treatment-related toxicity not significantly higher than that associated with chemotherapy and significantly lower than in allogeneic stem cell transplantation. The dilemma of best postremission therapy has not been resolved because of the paucity of randomized controlled studies, especially in various cytogenetic risk and age groups. Instead, the use of genetic randomization by donor availability, analysis of outcome based on intention-to-treat, and mixed populations in the registry data produce variable results. SUMMARY: ASCT has been associated with prolonged disease-free survival as compared to chemotherapy, especially in the favorable and intermediate risk groups. Advances in immunotherapy in AML may propel ASCT as a platform for various immunologic maneuvers. PMID- 26825698 TI - Optimal treatment strategies for high-risk acute promyelocytic leukemia. AB - PURPOSE OF REVIEW: Despite major advances in the treatment of acute promyelocytic leukemia (APL), high-risk APL still poses unique challenges. The purpose of this review is to outline current evidence for evaluation and management of high-risk APL and discuss areas of ongoing and future investigation. RECENT FINDINGS: With the changing treatment paradigm in APL and increasing use of arsenic trioxide (ATO), reports have questioned the relevance of classic prognostic factors. Despite advancements in therapy, early death remains a primary reason for treatment failure. A randomized, phase III trial demonstrated that all-trans retinoic acid + ATO is at least noninferior and may be superior to all-trans retinoic acid + chemotherapy in low/intermediate-risk APL. One phase III and multiple phase II trials have suggested a benefit of adding ATO to therapy of high-risk patients. Attempts at minimizing chemotherapy in high-risk disease have proven feasible with the use of gemtuzumab ozogamicin, but it is unlikely that cytotoxic chemotherapy will be completely eliminated in this patient population. SUMMARY: Treatment of high-risk APL has evolved significantly over the past 10 years and current scoring systems, management, and treatment regimens have been reviewed. There are as yet unresolved questions, including how to minimize early deaths and optimal therapy in an ATO era. PMID- 26825699 TI - Unfavorable-risk acute myeloid leukemia dissected. AB - PURPOSE OF REVIEW: Acute myeloid leukemia (AML) is an immensely heterogeneous disease based on the presence of varying combinations of morphologic, immunophenotypic, genetic, and molecular characteristics identified among those diagnosed with this disease. Although current therapeutic strategies provide a reasonable likelihood of achieving a complete remission for the majority of patients, relapse rates and subsequent disease-related mortality remain unacceptably high. Improved methods of risk stratification are needed to better identify patients at considerable risk of relapse in hopes of allowing for early therapeutic intervention and/or intensification that may lead to a higher likelihood of cure. The current status of risk stratification of AML and emerging technologies with potential to improve prognostic classification and outcomes are summarized in this review. RECENT FINDINGS: Refinement of our understanding of the impact of current pretreatment AML cytogenetic, immunophenotypic, and molecular aberrations to predict outcomes and guide therapeutic decision-making is ongoing. Emerging data suggest that incorporation of the degree of posttreatment response and/or the detection of minimal residual disease can improve the accuracy of risk stratification for individual patients. SUMMARY: Although pretreatment disease characteristics remain the hallmark of prognostication for AML patients, posttreatment parameters such as minimal residual disease assessment and degree of response to therapy possess the ability to further refine our identification of patients with unfavorable disease and thereby influence decisions regarding therapeutic planning. PMID- 26825700 TI - Is cure for chronic myeloid leukemia possible in the tyrosine kinase inhibitors era? AB - PURPOSE OF REVIEW: The advent of tyrosine kinase inhibitors (TKI) has remarkably changed the treatment of chronic myeloid leukemia (CML). Patients treated in chronic phase can enjoy an expected survival similar to the general population. In the last few years we have found that some patients with an excellent therapeutic response can have their TKI discontinued and still remain in molecular remission. RECENT FINDINGS: The fact that some patients can apparently have their therapy discontinued, and stay in remission for more than 2 years, is surprising, as in-vitro work suggests the CML cell is dependent on BCR-ABL signaling and mathematical models predict that extinction of the CML stem cell reservoir will take decades of therapy. However, given that unopposed BCR-ABL causes progression and CML cells can have a rather long latency (e.g., Hiroshima survivors), it may be some time until we can be completely assured that discontinuation is without risk. SUMMARY: If we can safely discontinue TKI in some patients, it will have a profound effect on both the strategy and medical economics of CML therapy. A key future finding will be factor(s) that predict which patients can be discontinued without relapse, thus targeting only the patients where discontinuation will be successful. PMID- 26825701 TI - The impact of home, work, and church environments on fat intake over time among rural residents: a longitudinal observational study. AB - BACKGROUND: Dietary behaviors are influenced by many individual and environmental factors. This study explores how dietary fat intake in high-risk midlife adults living in the rural south is influenced by three behavior settings, i.e. in the home, at work, and at church. METHODS: Self-report data were collected from rural African American or Caucasian adults age 40-70 at three time points at baseline, 6, and 12 months post baseline. Multilevel analyses investigated the impact of determinants of fat intake over time. RESULTS: Home and work environments varied significantly over time in regard to healthy eating while church environments remained stable. Age, gender, and self-efficacy for healthy eating were individual factors associated with fat intake. In the home, presence of more high fat items, a time-varying variable, was significant. In the work environment, having access to healthy foods as well as healthy eating programs has positive impact as did hearing healthy eating messages and availability of healthy foods at church. CONCLUSIONS: Understanding stability and variability of dietary fat intake from a social ecologic perspective will aid in identifying targets of change for intervention. Understanding which components of key behavior settings are dynamic and which are relatively stable will help to disentangle the complexity of multi-level determinants of dietary behavior. PMID- 26825702 TI - Beta EEG reflects sensory processing in active wakefulness and homeostatic sleep drive in quiet wakefulness. AB - Markers of sleep drive (<10 Hz; slow-wave activity and theta) have been identified in the course of slow-wave sleep and wakefulness. So far, higher frequencies in the waking electroencephalogram have not been examined thoroughly as a function of sleep drive. Here, electroencephalogram dynamics were measured in epochs of active wake (wake characterized by high muscle tone) or quiet wake (wake characterized by low muscle tone). It was hypothesized that the higher beta oscillations (15-35 Hz, measured by local field potential and electroencephalography) represent fundamentally different processes in active wake and quiet wake. In active wake, sensory stimulation elevated beta activity in parallel with gamma (80-90 Hz) activity, indicative of cognitive processing. In quiet wake, beta activity paralleled slow-wave activity (1-4 Hz) and theta (5 8 Hz) in tracking sleep need. Cerebral lactate concentration, a measure of cerebral glucose utilization, increased during active wake whereas it declined during quiet wake. Mathematical modelling of state-dependent dynamics of cortical lactate concentration was more precisely predictive when quiet wake and active wake were included as two distinct substates rather than a uniform state of wakefulness. The extent to which lactate concentration declined in quiet wake and increased in active wake was proportionate to the amount of beta activity. These data distinguish quiet wake from active wake. Quiet wake, particularly when characterized by beta activity, is permissive to metabolic and electrophysiological changes that occur in slow-wave sleep. These data urge further studies on state-dependent beta oscillations across species. PMID- 26825703 TI - Advances in Fecal Tests for Colorectal Cancer Screening. AB - OPINION STATEMENT: Colorectal cancer (CRC) forms an important public health problem, especially in developed countries. CRC screening tests can be used to identify asymptomatic individuals with CRC precursors and (early) cancer. Removal of these lesions reduces CRC incidence and prevents CRC-related mortality. There are a range of screening tests available, each with advantages and disadvantages. Stool screening tests can broadly be divided into fecal occult blood tests (FOBTs) and molecular biomarker test, such as DNA/RNA marker tests, protein markers, and fecal microbiome marker tests. Guaiac fecal occult blood tests (gFOBT) have been demonstrated in large randomized screening trials to reduce CRC mortality. Fecal immunochemical tests (FIT) have superior adherence, usability, and accuracy as compared to gFOBT. Advantage of the use of quantitative FITs in CRC screening programs is the cut-off level that can be adjusted. Molecular biomarker DNA tests have shown to detect significantly more cancers than FIT. By combining biomarker DNA tests with FIT, sensitivity for advanced adenomas can be increased significantly. However, it has lower specificity thus demands more colonoscopy resources, is more cumbersome, and costly. The adherence has not been assessed in population screening trials. For these reasons, FIT is therefore at present regarded as the preferred method of non-invasive CRC screening. This chapter will review the current status of fecal test-based CRC screening. PMID- 26825704 TI - Established and Emerging Treatment Options for Functional Heartburn and Chest Pain. AB - OPINION STATEMENT: Functional heartburn and functional chest pain of presumed esophageal origin are characterized by symptoms suggesting an esophageal origin, but negative work-up on routine investigations, including ruling out gastroesophageal reflux disease. Visceral hypersensitivity is a potentially unifying pathophysiological concept, thought to underlie these disorders. In addition, there is important overlap with other functional disorders and psychiatric co-morbidity. This review summarizes current concepts on definition, diagnosis, and treatment options for functional heartburn and functional chest pain of presumed esophageal origin. Antidepressants are frequently used in these conditions, where they are presumed to act as neuromodulators of visceral hypersensitivity. There is a need for high-quality trials evaluating the efficacy of antidepressants and more specific neuromodulators, such as pregabalin, in functional esophageal disorders. PMID- 26825705 TI - Computer modelling studies of the bilayer/water interface. AB - This review summarises high resolution studies on the interface of lamellar lipid bilayers composed of the most typical lipid molecules which constitute the lipid matrix of biomembranes. The presented results were obtained predominantly by computer modelling methods. Whenever possible, the results were compared with experimental results obtained for similar systems. The first and main section of the review is concerned with the bilayer-water interface and is divided into four subsections. The first describes the simplest case, where the interface consists only of lipid head groups and water molecules and focuses on interactions between the lipid heads and water molecules; the second describes the interface containing also mono- and divalent ions and concentrates on lipid-ion interactions; the third describes direct inter-lipid interactions. These three subsections are followed by a discussion on the network of direct and indirect inter-lipid interactions at the bilayer interface. The second section summarises recent computer simulation studies on the interactions of antibacterial membrane active compounds with various models of the bacterial outer membrane. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Rog. PMID- 26825706 TI - Effects of probiotics on child growth: a systematic review. AB - BACKGROUND: Child undernutrition has short and long term consequence for both individuals and society. Previous studies show probiotics may promote child growth and have an impact on under-nutrition. METHODS: A systematic review of the literature was carried out on three electronic databases to assess evidence. The outcome measured was change in weight or height. A narrative analysis was conducted due to heterogeneity of included studies. RESULTS: Twelve studies were included in the review of which ten were randomised controlled trials. A total of 2757 children were included, with 1598 from developing countries. The studies varied in type and quantity of probiotics given, duration of interventions, characteristics of participants, setting and units of outcome measures. Overall, five studies found a positive effect of probiotics on child growth. All five were conducted in developing countries with four studies conducted in mostly under nourished children and one in well-nourished children. No significant effect on growth was found in the seven studies that were conducted in developed countries. CONCLUSION: The limited evidence suggests that probiotics have the potential to improve child growth in developing countries and in under-nourished children. More research is needed to explore this further. PMID- 26825707 TI - Janus kinase inhibition lessens inflammation and ameliorates disease in murine models of hemophagocytic lymphohistiocytosis. AB - Hemophagocytic lymphohistiocytosis (HLH) comprises an emerging spectrum of inherited and noninherited disorders of the immune system characterized by the excessive production of cytokines, including interferon-gamma and interleukins 2, 6, and 10 (IL-2, IL-6, and IL-10). The Janus kinases (JAKs) transduce signals initiated following engagement of specific receptors that bind a broad array of cytokines, including those overproduced in HLH. Based on the central role for cytokines in the pathogenesis of HLH, we sought to examine whether the inhibition of JAK function might lessen inflammation in murine models of the disease. Toward this end, we examined the effects of JAK inhibition using a model of primary (inherited) HLH in which perforin-deficient (Prf1(-/-)) mice are infected with lymphocytic choriomeningitis virus (LCMV) and secondary (noninherited) HLH in which C57BL/6 mice receive repeated injections of CpG DNA. In both models, treatment with the JAK1/2 inhibitor ruxolitinib significantly lessened the clinical and laboratory manifestations of HLH, including weight loss, organomegaly, anemia, thrombocytopenia, hypercytokinemia, and tissue inflammation. Importantly, ruxolitinib treatment also significantly improved the survival of LCMV-infectedPrf1(-/-)mice. Mechanistic studies revealed that in vivo exposure to ruxolitinib inhibited signal transducer and activation of transcription 1-dependent gene expression, limited CD8(+)T-cell expansion, and greatly reduced proinflammatory cytokine production, without effecting degranulation and cytotoxic function. Collectively, these findings highlight the JAKs as novel, druggable targets for mitigating the cytokine-driven hyperinflammation that occurs in HLH. These observations also support the incorporation of JAK inhibitors such as ruxolitinib into future clinical trials for patients with these life-threatening disorders. PMID- 26825708 TI - A subset of high-titer anti-factor VIII A2 domain antibodies is responsive to treatment with factor VIII. AB - The primary B-cell epitopes of factor VIII (fVIII) are in the A2 and C2 domains. Within the C2 domain, antibody epitope and kinetics are more important than inhibitor titer in predicting pathogenicity in a murine bleeding model. To investigate this within the A2 domain, the pathogenicity of a diverse panel of antihuman fVIII A2 domain monoclonal antibodies (MAbs) was tested in the murine model. MAbs were injected into hemophilia A mice, followed by injection of human B domain-deleted fVIII. Blood loss after a 4-mm tail snip was measured. The following anti-A2 MAbs were tested: high-titer type 1 inhibitors 4A4, 2-76, and 1D4; 2-54, a high-titer type 2 inhibitor; B94, a type 2 inhibitor; and noninhibitory MAbs GMA-012, 4C7, and B25. All high-titer type 1 MAbs produced blood loss that was significantly greater than control mice, whereas all non inhibitory MAbs produced blood loss that was similar to control. The type 2 MAbs were not pathogenic despite 2-54 having an inhibitor titer of 34 000 BU/mg immunoglobulin G. In addition, a patient with a high-titer type 2 anti-A2 inhibitor who is responsive to fVIII is reported. The discrepancy between inhibitor titer and bleeding phenotype combined with similar findings in the C2 domain stress the importance of inhibitor properties not detected in the standard Bethesda assay in predicting response to fVIII therapy. PMID- 26825709 TI - HIF-1alpha regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment. AB - Hypoxia-inducible transcription factors (HIFs) regulate a wide array of adaptive responses to hypoxia and are often activated in solid tumors and hematologic malignancies due to intratumoral hypoxia and emerging new layers of regulation. We found that in chronic lymphocytic leukemia (CLL), HIF-1alpha is a novel regulator of the interaction of CLL cells with protective leukemia microenvironments and, in turn, is regulated by this interaction in a positive feedback loop that promotes leukemia survival and propagation. Through unbiased microarray analysis, we found that in CLL cells, HIF-1alpha regulates the expression of important chemokine receptors and cell adhesion molecules that control the interaction of leukemic cells with bone marrow and spleen microenvironments. Inactivation of HIF-1alpha impairs chemotaxis and cell adhesion to stroma, reduces bone marrow and spleen colonization in xenograft and allograft CLL mouse models, and prolongs survival in mice. Of interest, we found that in CLL cells, HIF-1alpha is transcriptionally regulated after coculture with stromal cells. Furthermore, HIF-1alpha messenger RNA levels vary significantly within CLL patients and correlate with the expression of HIF-1alpha target genes, including CXCR4, thus further emphasizing the relevance of HIF-1alpha expression to CLL pathogenesis. PMID- 26825710 TI - The ubiquitin ligase HERC4 mediates c-Maf ubiquitination and delays the growth of multiple myeloma xenografts in nude mice. AB - The transcription factor c-Maf is extensively involved in the pathophysiology of multiple myeloma (MM), a fatal malignancy of plasma cells. In the present study, affinity chromatography and mass spectrometry were used to identify c-Maf ubiquitination-associated proteins, from which the E3 ligase HERC4 was found to interact with c-Maf and catalyzed its polyubiquitination and subsequent proteasome-mediated degradation. HERC4 mediated polyubiquitination at K85 and K297 in c-Maf, and this polyubiquitination could be prevented by the isopeptidase USP5. Further analysis on the NCI-60 cell line collection revealed that RPMI 8226, a MM-derived cell line, expressed the lowest level of HERC4. Primary bone marrow analysis revealed HERC4 expression was high in normal bone marrow, but was steadily decreased during myelomagenesis. These findings suggested HERC4 played an important role in MM progression. Moreover, ectopic HERC4 expression decreased MM proliferation in vitro, and delayed xenograft tumor growth in vivo. Therefore, modulation of c-Maf ubiquitination by targeting HERC4 may represent a new therapeutic modality for MM. PMID- 26825711 TI - Uncompromised 10-year survival of oldest old carrying somatic mutations in DNMT3A and TET2. PMID- 26825714 TI - The Irrelevance of Factor Analysis for the Study of Group Differences. PMID- 26825713 TI - Guttman's "Last Paper": A Commentary and Discussion Editor's Introduction. PMID- 26825715 TI - Commentary on Guttman: The Irrelevance of Factor Analysis for the Study of Group Differences. PMID- 26825712 TI - Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure. AB - Hepatic veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). Untreated hepatic VOD/SOS with multi-organ failure (MOF) is associated with >80% mortality. Defibrotide has shown promising efficacy treating hepatic VOD/SOS with MOF in phase 2 studies. This phase 3 study investigated safety and efficacy of defibrotide in patients with established hepatic VOD/SOS and advanced MOF. Patients (n = 102) given defibrotide 25 mg/kg per day were compared with 32 historical controls identified out of 6867 medical charts of HSCT patients by blinded independent reviewers. Baseline characteristics between groups were well balanced. The primary endpoint was survival at day +100 post-HSCT; observed rates equaled 38.2% in the defibrotide group and 25% in the controls (23% estimated difference; 95.1% confidence interval [CI], 5.2-40.8;P= .0109, using a propensity-adjusted analysis). Observed day +100 complete response (CR) rates equaled 25.5% for defibrotide and 12.5% for controls (19% difference using similar methodology; 95.1% CI, 3.5-34.6;P= .0160). Defibrotide was generally well tolerated with manageable toxicity. Related adverse events (AEs) included hemorrhage or hypotension; incidence of common hemorrhagic AEs (including pulmonary alveolar [11.8% and 15.6%] and gastrointestinal bleeding [7.8% and 9.4%]) was similar between the defibrotide and control groups, respectively. Defibrotide was associated with significant improvement in day +100 survival and CR rate. The historical-control methodology offers a novel, meaningful approach for phase 3 evaluation of orphan diseases associated with high mortality. This trial was registered at www.clinicaltrials.gov as #. PMID- 26825716 TI - Extension of Guttman's Result From g to PC1. PMID- 26825717 TI - Spearman's Hypothesis: Methodology and Evidence. PMID- 26825718 TI - Guttman on Factor Analysis and Group Differences: A Comment. PMID- 26825719 TI - The Relevance of Factor Analysis for the Study of Group Differences. PMID- 26825720 TI - Reaction to Other Commentaries. PMID- 26825721 TI - Second Round Commentary on Guttman. PMID- 26825723 TI - On Shonemann on Guttman on Jensen, via Lewontin. PMID- 26825722 TI - More on Psychometric g and "Spearman's Hypothesis". PMID- 26825724 TI - The "Spearman Hypothesis" is False. PMID- 26825725 TI - Automated Fitting of Nonstandard Models. AB - A method for automated parameter estimation and testing of fit of nonstandard models for mean vectors and covariance matrices is described. Nonlinear equality and inequality constraints on the parameters of the model are allowed for. All the user will need to provide are subroutines to evaluate the mean vector and covariance matrix according to the model and, if required, the constraint functions. Subroutines for derivatives need not be provided. Some applications are described. PMID- 26825726 TI - Potential to breed for mycorrhizal association in durum wheat. AB - The selection of genotypes under high soil fertility may alter the effectiveness of mycorrhizal symbioses naturally forming between crop plants and the mycorrhizal fungi residing in cultivated fields. We tested the hypothesis that the mycorrhizal symbiosis of 5 landraces functions better than the mycorrhizal symbiosis of 27 cultivars of durum wheat that were bred after the development of the fertilizer industry. We examined the development of mycorrhiza and the response of these genotypes to mycorrhiza formation after 4 weeks of growth under high and low soil fertility levels in the greenhouse. The durum wheat genotypes were seeded in an established extraradical hyphal network of Rhizophagus irregularis and in a control soil free of mycorrhizal fungi. The percentage of root length colonized by mycorrhizal fungi was lower in landraces (21%) than in cultivars (27%; P = 0.04) and in the most recent releases (29%; P = 0.02), which were selected under high soil fertility levels. Plant growth response to mycorrhiza varied from -36% to +19%. Overall, durum wheat plant breeding in Canada has increased the mycorrhizal development in wheat grown at a low soil fertility level. However, breeding had inconsistent effects on mycorrhizal development and has led to the production of cultivars with patterns of regulation ranging from unimproved to inefficient. PMID- 26825727 TI - Erratum to: Prophylactic vitamin D supplementation in ovarian hyperstimulation syndrome: an animal study. PMID- 26825728 TI - Retraction Note to: Therapeutic effects of metformin and laparoscopic ovarian drilling in treatment of clomiphene and insulin-resistant polycystic ovary syndrome. PMID- 26825729 TI - Erratum to: Myo-inositol is a promising treatment for the prevention of ovarian hyperstimulation syndrome (OHSS): an animal study. PMID- 26825730 TI - Prenatal diagnosis of fetal akinesia deformation sequence (FADS): a study of 79 consecutive cases. AB - PURPOSE: Fetal akinesia deformation sequence (FADS) is a clinically and genetically heterogenous disorder. In this study, the different sonographic abnormalities are described in a larger number of affected fetuses. METHODS: This retrospective study included 79 cases of suspected FADS observed in our tertiary referral center between January 2001 and February 2015. Electronic stored reports and images of the examination were reviewed as well as autopsy reports and pediatric charts. RESULTS: In the study population (mean gestational age 23 + 4 weeks) consanguinity, multiple miscarriages or positive family history were present in 31.6 % of cases. Abnormalities of the facial profile (58.3 %) and ankle joint (83.6 %) were detected in the majority of cases. Contractures variably involved knee-, ankle-, wrist- and elbow joint and fingers with no distinct patterns. Additional malformations, most commonly of the brain, were found in 44.3 % of cases. Diagnosis before 20 weeks was associated with nuchal edema in 62.5 and hydrops in 31.3 %. In fetuses evaluated later than 24 weeks, IUGR, increased amniotic fluid or thorax hypoplasia were diagnosed, in 31, 58.8 and 37.9 %, respectively. Termination of pregnancy was requested in 86.1 %, 11 (13.9 %) children were live born. No underlying genetic cause was established, but in one asymptomatic mother myasthenia gravis was revealed. CONCLUSIONS: Fetal akinesia presents with heterogeneous sonographic findings, mostly affecting the profile, elbow-, knee-, ankle joint, wrists and fingers; in most of cases of sporadic nature. Whereas hydrops fetalis and nuchal edema were earlier signs, thorax hypoplasia, polyhydramnios and IUGR were found later in pregnancy. PMID- 26825731 TI - Early induction of labor in high-risk intrahepatic cholestasis of pregnancy: what are the costs? AB - PURPOSE: Induction of labor among pregnant women with high levels of total bile acid (TBA) is common among clinicians. We examined, if women with intrahepatic cholestasis of pregnancy (ICP) and TBA >= 40 MUmol/l have a higher risk of maternal-fetal complications, when labor is induced at 37 weeks of gestation, compared with induction of labor at term in women with low-risk ICP. METHODS: Retrospective cohort study of 16,185 women delivering at Roskilde University Hospital in the period 2006-2011. Women with high-risk ICP (TBA >= 40 MUmol/l) had labor induced at 37 weeks of gestation; women with low-risk ICP (TBA < 40 MUmol/l) at term. OUTCOMES: Mode of delivery, duration of induction procedures, highest level of TBA and alanine aminotransferase (ALT) and for the neonates: Apgar scores at 5 min, umbilical cord pHs and SBEs, NICU admissions and birthweights. RESULTS: The incidences of ICP was 1.2 % (95 % CI 1.05-1.39 %) altogether and for high-risk ICP 0.4 % (95 % CI 0.27-0.46 %). No difference was found in mode of delivery, length of induction of labor nor in neonatal outcomes, except for an expected difference in birthweight. In high-risk ICP, ALT was not raised in 10.3 % (95 % CI 2.5-18.2 %). CONCLUSION: Early induction of labor at 37 weeks of gestation seems justified in high-risk ICP, as, except for abbreviating gestational age by 9 days with 296 g smaller babies, induction of labor was not followed by detectable maternal-fetal disadvantages and is favored by an expected major reduction in ICP stillbirth risk. PMID- 26825732 TI - Alteration of STR profiles in ovarian carcinoma cells during primary culture. AB - PURPOSE: Cell authentication is a necessary procedure to avoid scientific data from cell culture experiments with cross-contamination or false classification. A genetic fingerprint pattern of a specimen by short tandem repeats (STR) is self evident. Due to high amount of chromosomal rearrangements, known in epithelia ovary cancer cells and the instable STR pattern described in other tumour entities like leukaemia, this study explores the suitability of STR profiling for primary cultured epithelial ovary cancer cells. METHODS: STR profiles of epithelial ovary cancers of 16 patients were compared with corresponding blood and corresponding primary cell cultures. The primary cell cultures of epithelial ovary tumours were passaged up to 28 times. In between, cultures were cryo conserved and recultured again, two to five times per patient. RESULTS: In two cases, the STR pattern of tumour lost alleles (1/16 and 3/16) in comparison of corresponding STR-pattern from blood. In comparison to blood, cell culture of a third case, lost four alleles (4/16) accompanied with morphologic changes after 14th passage. It is equal after cryo conservation of the seventh passage from the same patient. The only changes in STR profiles we recognized are losses of alleles. Remaining STR markers allow authentication. CONCLUSIONS: Very likely, the allelic drop-outs beyond passage 14 assume complex genetic losses of heterozygosis resulting in changed growth behaviour of cells. All other STR profiles of remaining 15 patients analysed in this study are stable over all passages and freeze-thaw processes. Thus, ovary cancer cell cultures in research should be authenticated by STR-profile in general. PMID- 26825733 TI - Association between vitamin D status and the risk of gestational diabetes mellitus: a meta-analysis. AB - PURPOSE: Vitamin D is widely used for bone growth and normal insulin secretion; however, the association between vitamin D status and gestational diabetes risk is controversial. This meta-analysis aimed to quantitatively evaluate the association between vitamin status and risk of gestational diabetes. METHODS: We performed a systematic search on the PubMed, EmBase, and Cochrane Library databases in January 2015 to obtain observational studies studying gestational diabetes risk in relation to vitamin D status. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to measure the association between vitamin D status and the risk of gestational diabetes. RESULTS: A total of 20 observational studies were included in the final analysis containing 16,515 individuals. Overall, maternal vitamin D insufficiency was found to be associated with a greater risk of gestational diabetes (RR 1.45; 95 % CI 1.15-1.83; P < 0.001). Subgroup analysis indicated that this association might differ based on countries, study design, assessment of vitamin D levels, sample size, age at baseline, adjusted models, and study quality. CONCLUSIONS: This meta-analysis revealed that maternal vitamin D insufficiency is associated with increased risk of gestational diabetes. PMID- 26825734 TI - Guido C. Currarino, MD, Dec. 17, 1920 - Dec. 20, 2015. PMID- 26825735 TI - Pulmonary vasculature directed adenovirus increases epithelial lining fluid alpha 1 antitrypsin levels. AB - BACKGROUND: Gene therapy for inherited serum deficiency disorders has previously been limited by the balance between obtaining adequate expression and causing hepatic toxicity. Our group has previously described modifications of a replication deficient human adenovirus serotype 5 that increase pulmonary vasculature transgene expression. METHODS: In the present study, we use a modified pulmonary targeted adenovirus to express human alpha-1 antitrypsin (A1AT) in C57BL/6 J mice. RESULTS: Using the targeted adenovirus, we were able to achieve similar increases in serum A1AT levels with less liver viral uptake. We also increased pulmonary epithelial lining fluid A1AT levels by more than an order of magnitude compared to that of untargeted adenovirus expressing A1AT in a mouse model. These gains are achieved along with evidence of decreased systemic inflammation and no evidence for increased inflammation within the vector targeted end organ. CONCLUSIONS: In addition to comprising a step towards clinically viable gene therapy for A1AT, maximization of protein production at the site of action represents a significant technical advancement in the field of systemically delivered pulmonary targeted gene therapy. It also provides an alternative to the previous limitations of hepatic viral transduction and associated toxicities. PMID- 26825737 TI - JAK2 mutation and acute coronary syndrome complicated with stent thrombosis. AB - Acute coronary syndrome (ACS) could be a precious opportunity for patients to reveal concealed diseases other than conventional risk factors for ACS, such as hypertension, dyslipidemia, diabetes mellitus, etc. In the setting of ACS, the intracoronary and systemic prothrombotic environment has led to an increase in the risk of stent thrombosis of which mortality was higher among patients with ACS, especially with the highest mortality in patients with ST elevation myocardial infarction. The some specific conditions which were concealed beyond the cardiovascular pathophysiology except well-known risk factors for ACS and stent thrombosis might involve the onset of ACS. We describe a case of a 64-year old man who was admitted to intensive care unit for chest pain. This case found the possibility that polycythemia vera with Janus kinase 2 (JAK2) V617F mutation might be a underlying disease of ACS with stent thrombosis, and highlighted the importance of recognizing polycythemia vera with JAK2 V617F mutation as concealed disease for cardiologists. We would like to report and review the relationship between ACS and polycythemia vera with JAK2 V617F mutation. PMID- 26825736 TI - Long-term effects of L- and N-type calcium channel blocker on uric acid levels and left atrial volume in hypertensive patients. AB - Left ventricular (LV) diastolic dysfunction is associated with hypertension and hyperuricemia. However, it is not clear whether the L- and N-type calcium channel blocker will improve LV diastolic dysfunction through the reduction of uric acid. The aim of this study was to investigate the effects of anti-hypertensive therapy, the L- and N-type calcium channel blocker, cilnidipine or the L-type calcium channel blocker, amlodipine, on left atrial reverse remodeling and uric acid in hypertensive patients. We studied 62 patients with untreated hypertension, randomly assigned to cilnidipine or amlodipine for 48 weeks. LV diastolic function was assessed with the left atrial volume index (LAVI), mitral early diastolic wave (E), tissue Doppler early diastolic velocity (E') and the ratio (E/E'). Serum uric acid levels were measured before and after treatment. After treatment, systolic and diastolic blood pressures equally dropped in both groups. LAVI, E/E', heart rate and uric acid levels decreased at 48 weeks in the cilnidipine group but not in the amlodipine group. The % change from baseline to 48 weeks in LAVI, E wave, E/E' and uric acid levels were significantly lower in the cilnidipine group than in the amlodipine group. Larger %-drop in uric acid levels were associated with larger %-reduction of LAVI (p < 0.01). L- and N-type calcium channel blocker but not L-type calcium channel blocker may improve LV diastolic function in hypertensive patients, at least partially through the decrease in uric acid levels. PMID- 26825738 TI - Effect of dietary Schizochytrium microalga oil on selected markers of low-grade inflammation in rats. AB - The objective of the present study was to evaluate a potential of Schizochytrium microalga oil to alleviate possible negative effects of high-fat-high-energy diets. Forty adult male rats (Wistar Albino) were fed 7 weeks the diet containing beef tallow + evaporated sweetened milk (diet T) intended to cause mild obesity and low-grade systemic inflammation. Consequently, the animals were divided into four groups by 10 animals each and fed either the T-diet (control) or the diet containing 6% of safflower oil (S), 6% of fish oil (F) and 6% of Schizochytrium microalga oil (A), respectively, for another 7 weeks. The A-diet decreased (p < 0.05) live weight to 86% and glycaemia to 85% of control, respectively; an effect of the S- and F-diet on these markers was insignificant (p > 0.05). In comparison with control, higher (p < 0.05) deposition of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) in the epididymal adipose tissue (EAT) of the A-rats correlated with increased (p < 0.05) plasma adiponectin concentration, but it was without the effect (p > 0.05) on cellular adiponectin content in the EAT. Higher (p < 0.05) EPA+DHA deposition in the liver of the A-rats correlated with higher expression (149% of control; p < 0.05) of the gene coding for peroxisome proliferator-activated receptor gamma, and with lower expression (82% and 66%; p < 0.05) of the genes coding for adiponectin receptors AdipoR1 and AdipoR2; no relationship to the expression of receptor GPR120 was found. The A-diet did not affect amount of the nuclear fraction of the nuclear factor kappa B in the liver, but increased plasma level of anti-inflammatory cytokine TGF-beta1 (p < 0.05). The presented data agree with results of other in vivo rodent and human studies, but not with literature data regarding in vitro experiments: it can be concluded that the effects of dietary oils on inflammatory markers need further investigation. PMID- 26825739 TI - The Management of Nonsyndromic, Isolated Sagittal Synostosis. AB - AIM: Isolated sagittal synostosis is the commonest form of craniosynostosis. The reasons for surgery are to normalize the head shape and to increase the cranial volume, thus reducing the risk of raised intracranial pressure and allowing for normal brain development. It has been suggested that sagittal synostosis may impair neuropsychological development. This systematic review appraised the literature on the management of sagittal synostosis. METHODS: A literature search was performed with the assistance of a professional librarian. Studies selected had to satisfy the criteria set by PICO (patients, intervention, comparison, and outcome). Cranial index and neuropsychological outcome were used as outcome measures. MINORS was used to assess the methodological quality of the selected articles. A score of 75% was deemed to be of satisfactory quality, and the quality of the evidence from the selected studies was graded using the GRADE system. RESULTS: One hundred forty-eight articles were initially identified. Only 6 articles fulfilled the PICO criteria and scored a minimum of 75% on MINORS. Four studies compared 1 technique to another with documented cranial indices. Two studies compared 1 group to another and assessed the neuropsychological development. According to GRADE, the quality of evidence was deemed to be very low. CONCLUSIONS: This systematic review assessed cranial index and neuropsychological outcome following surgery for isolated, nonsyndromic sagittal synostosis. The quality of the evidence in the published literature was noted to be of very low quality. There is a need for better-designed, prospective studies to guide surgeons involved in management of sagittal synostosis. PMID- 26825740 TI - Outer Fascia of Orbicularis Oculi Muscle as an Anchoring Target Tissue in Double Eyelid Surgery. AB - BACKGROUND: Natural adhesion between the levator aponeurosis and the subcutaneous layer in the upper lid is essential for an aesthetically pleasing double eyelid. The study aims to emphasize the outer fascia of orbicularis oculi muscle (OFOOM) as a fixation point on the double eyelid surgery. METHODS: The authors examined the detailed anatomy of the anterior lamella microscopically during 28 cases of primary double eyelid surgery. Three cadaveric dissections were performed adjunctively to compare the dynamic status in the upper lids. Subdermal tissue components and tissue changes in the upper lids were observed in 64 eyelids from secondary revisional cases who had performed an incisional technique previously. The authors also compared the locations of threads in the anterior lamella in 36 eyelids on which a nonincisional surgery technique had previously been used. RESULTS: At the preferred crease zone in the upper lid, a definite anatomic structure, OFOOM was found between the skin and the orbicularis oculi muscle (OOM). The supratarsal creases created by the incisional technique showed that all of the anterior lamella components were fused tightly together by scar tissue. Examination of the 36 supratarsal creases created by the nonincisional technique showed that threads did not exist in the dermal layer, but were mainly within the OFOOM in 20 eyelids and mainly within the OOM layer in 16 eyelids. CONCLUSIONS: To produce satisfactory results during double eyelid surgery, the authors recommend direct suture fixation of the levator aponeurosis to the OFOOM, and not to the dermis or OOM. PMID- 26825741 TI - The Extended Subfrontal and Fronto-Orbito-Zygomatic Approach in Skull Base Meningioma Surgery: Clinical, Radiologic, and Cosmetic Outcome. AB - OBJECTIVE: To review the outcome and cosmetic results of patients undergoing extended subfrontal and fronto-orbito-zygomatic craniotomy for resection of skull base meningiomas. METHODS: All surgeries were performed in cooperation with an oral and maxillofacial surgeon between 2006 and 2012. Clinical presentation, surgical techniques and complications, cosmetic, clinical, and radiologic outcomes are presented. RESULTS: This study included 25 consecutive patients with 26 operations. Total and subtotal tumor removal was obtained in 19 (73.1%) and 7 (26.9%) patients, respectively. Permanent postoperative complications were seen in 5 (19.2%) patients. Eight of 10 patients with preoperative visual impairment showed recovery at 6 months follow-up. Anosmia was improved in 50% and no worsening was seen in any case of hyposmia. All patients showed improved or complete correction of exophthalmos, cognitive deficits, and epilepsy. One patient (3.8%) developed a postoperative ptosis. No mortality was documented. All patients reported a favorable cosmetic satisfactory score over 6 (8.67 +/- 1.6). Tumor recurrence rate was 7.7% (n = 2). CONCLUSIONS: The extended subfrontal and fronto-orbito-zygomatic approach, used for resection of meningiomas located in the orbita and the skull base can provide better visibility of the tumor. In addition, these approaches lead to highly satisfying cosmetic and clinical results. PMID- 26825743 TI - Orthognathic Surgery: Outcome in a Facebook Group. AB - The literature shows that the indications for orthognathic surgery (OS) are often functional problems and unsatisfactory facial esthetics. This study investigated the esthetic outcomes and overall satisfaction following OS. Somatosensory change is a relatively common complication and its influence on the level of satisfaction was studied. The social-networking web site Facebook was used to identify the study population. An online questionnaire was performed using the website SurveyMonkey. In all, 105 (9%) respondents from the Danish Facebook group about OS, called Kaebeoperation (jaw surgery), were enrolled in the study. The respondents consisted of 12 men and 93 women, with a mean age of 27 +/- 9 years. Fifty-four percent replied that esthetic concerns were the reason for the OS. Eighty-four percent reported improvement in facial esthetics after the OS. Men indicated a higher degree of improvement in beauty than women (P = 0.030). Sixty four percent replied that their attractiveness had been increased after OS. Eighty-six percent were happy with the results and 89% would recommend the surgery to others in need. No significant differences in esthetic results and satisfaction were seen with regard to sex, age, and somatosensory change. High satisfaction and improvement in facial esthetic after OS were seen. Young patients (16-25 years) and men indicated a higher degree of satisfaction than old (>25 years) patients and women. The use of social media seems to be an interesting platform for qualitative scientific research in certain age groups. Further prospective and objective studies about the esthetic improvement after OS should be performed. PMID- 26825742 TI - A Reduction in Radiation Exposure During Pediatric Craniofacial Computed Tomography. AB - BACKGROUND: Radiation exposure during computed tomography (CT) evaluation in children is the subject of growing professional and public concern. The authors previously demonstrated an 18% reduction in effective radiation dose during craniofacial CT imaging using a modified head position ("exaggerated sniff"), without any compromise of image diagnostic quality. The current study reports additional reduction of radiation exposure using a commercially available iterative reconstruction CT technique. METHODS: This single-institution, retrospective cohort study compared the overall effective radiation dose received during elective pediatric craniofacial CT imaging. Patients imaged using the iterative reconstruction and exaggerated sniff protocol combined (January 2010 through December 2013) were compared with those undergoing imaging with the exaggerated sniff position alone, between October 2008 and January 2010. RESULTS: A total of 325 patients who underwent CT imaging with the exaggerated sniff position, decreased dose and iterative reconstruction protocol experienced an average effective radiation dose of 1.22 mSv (47% reduction), compared with 2.32 mSv for the sniff-position alone group. Age-matched reference patients not treated using either protocol received an average of 2.82 mSv. This represents a 56.7% average radiation dose reduction for combined sniff position and iterative reconstruction patients compared with reference patients and 47.4% reduction compared with the sniff-position alone group. Image quality of both bone and brain windows was equivalent. CONCLUSIONS: Altering head position and use of iterative reconstruction technique with a reduced radiation protocol diminishes CT imaging-related effective radiation dose by approximately 50% in children undergoing elective cranial CT imaging for craniofacial disorders. PMID- 26825744 TI - Combined Intralesional Neodymium-Doped Yttrium Aluminium Garnet Laser and Intratumoral Ligation as Curative Treatment for Craniofacial Arteriovenous Malformations. AB - Craniofacial arteriovenous malformation (AVM), although very rare, has been a very difficult problem to treat especially when it is large and involves important structures. Surgical resection often results in unacceptable complications but still not curative. At our institution, treatment by combined intralesional neodymium-doped yttrium aluminium garnet laser and intratumoral ligation has been successful in venous malformation. This minimally invasive technique was then applied to more challenging AVM on the head and neck. Disease control was studied using clinical parameters and magnetic resonance imaging.Four patients with moderate-to-severe (Schobinger 2-4) craniofacial AVM were treated by this technique from 2001 to 2011. Patient age ranged from 2 to 51 years (mean: 25 years). After 2 to 4 treatments and follow-up period of 1456 days, 3 (75%) were cured. One of them was infant with huge mass and secondary pulmonary hypertension. Clinical cure was achieved after 3 treatments without residual cardiovascular compromise. The other patient (25%) had cheek mass with intraorbital involvement. The authors did not treat periorbital lesion so as to avoid triggering intraorbital spreading. The rest of the cheek lesion was clinically and radiologically cured.Laser energy setting, ablative technique, and skin cooling are the main factors determining the success. Individualized laser settings and properly set endpoints can increase treatment effectiveness in shorter period. In conclusion, this minimally invasive technique was successful in curing AVM without complication. With more clinical study and development of soft tissue monitoring tools, it is possible that intralesional laser could become the treatment of choice for all cutaneous AVM. PMID- 26825745 TI - Magnetic Resonance Image Evaluation of Temporomandibular Joint Osteophytes: Influence of Clinical Factors and Artrogenics Changes. AB - This research aims to examine the presence of osteophyte in patients with arthrogenic temporomandibular disorders through magnetic resonance imaging (MRI); to investigate the influence of sex and clinical symptoms in its prevalence; and the position of the osteophytes in the condyle. The study was based on 100 MRI and on reports of patients, which corresponded to the evaluation of 200 joints. Patients of both sexes were aged from 18 to 82 years (average = 49.48) and were subjected to the aforementioned examination from January 2006 to March 2009. The assessment considered the type of disc displacement, the presence of effusion, bone marrow edema, condyle changes, joint noise and pain. The MRI machine used was the GE Signa HDX (General Electric, Milwaukee, WI), with T1 and T2-weighted, 1.5 T magnetic field, sagittal oblique (mouth closed, mouth open) and coronal (mouth closed) imaging, with spherical surface coil and an asymmetric matrix. All images were interpreted by an experienced radiologist. A total of 28% (n = 56) of the temporomandibular joints showed osteophytes on the anterior surface of the mandible. No relationship was found between sex and osteophytes. The authors found a statistically significant difference between osteophytes and disc displacement without reduction (P < 0.001). The presence of osteophytes suggested a possible cause and effect relationship between osteoarthritis and disc displacement without reduction; the osteophyte was always located in the anterior surface of condyle, regardless of the sex variable; no significant difference was found between osteophytes and the main complaints of the patient. PMID- 26825746 TI - Social and Support Services Offered by Cleft and Craniofacial Teams: A National Survey and Institutional Experience. AB - BACKGROUND: A multidisciplinary approach to patients with craniofacial abnormalities is the standard of care by the American Cleft Palate-Craniofacial Association (ACPA). The standards of team care, however, do not require provision of social support services beyond access to a social worker. The purpose of this investigation is to study social support services provided by ACPA teams, funding sources for services, and family interest in services. METHODS: A survey was submitted to ACPA cleft and craniofacial team leaders (N = 161), which evaluated the provision of potentially beneficial social support services, and their funding sources. A second survey administered to patient families at our institution gauged their level of interest in these services. Statistical analysis evaluated the level of interest among services. RESULTS: Seventy-five of 161 (47%) teams and 39 of 54 (72%) families responded to the surveys. Services provided included scholarships (4%), summer camp (25%), social media (32%), patient support groups (36%), parties (42%), parent support groups (46%), other opportunities (56%), and social workers (90%). The majority of funding for social workers was by the institution (61%) whereas funding for ancillary services varied (institution, team, fundraisers, grants, and other sources). Families indicated an average interest of 2.4 +/- 1.41 for support groups, 2.5 +/- 1.63 for summer camps, 2.92 +/- 1.66 for parties, 3.16 +/- 1.65 for social media, and 3.95 +/- 1.60 for scholarships (P value <0.05). CONCLUSIONS: The ACPA standards of team care do not require teams to provide social support services beyond access to a social worker. Among our survey respondents, the authors found that in addition to a social worker, teams offered social support services, which were not required. The social worker position is usually institutionally funded, whereas funding sources for additional services varied. Respondents at our center desired additional social support services. The authors recommend a hybrid model of hospital and nonhospital funding to provide social and support services to patients with craniofacial deformities. PMID- 26825747 TI - Comparison Between Interactive Closest Point and Procrustes Analysis for Determining the Median Sagittal Plane of Three-Dimensional Facial Data. AB - OBJECTIVE: To compare 2 digital methods to determine median sagittal plane of three-dimensional facial data-the interactive closest point algorithm and Procrustes analysis. METHODS: The three-dimensional facial data of the 30 volunteers were got by the Face Scan 3D optical sensor (3D-Shape GmbH, Erlangen, Germany), and then were input to the reverse engineering software Imageware 13.0 (Siemens, Plano, TX) and Geomagic 2012 (Cary, NC). Their mirrored data were acquired and superimposed with the original data by the methods of interactive closest points and Procrustes analysis. The median sagittal planes of the 2 methods were extracted from the original and mirrored facial data respectively, 3 asymmetry indices were measured for comparison. Differences between the facial asymmetry indices of the 2 methods were evaluated using the paired sample t-test. RESULTS: In terms of the 3 asymmetry indices, there were no significant differences between interactive closest points and Procrustes analysis for extracting median sagittal plane from three-dimensional facial data.(t = 0.0.060, P = 0.953 for asymmetry index (AI) 1, t = -0.926, P = 0.362 for AI 2, t = 1.1172, P = 0.0.251 for AI 3). CONCLUSIONS: In this evaluation of 30 subjects, the Procrustes analysis and the interactive closest point median-sagittal planes were similar in terms of the 3 asymmetry indices. Thus, Procrustes analysis and interactive closest point can both be used to abstract median sagittal plane from three-dimensional facial data. PMID- 26825748 TI - Maxillary Reconstruction for Sinus Lift Complications With Oro-Antral Fistula: The Le Fort I Approach. AB - Although sinus lift procedures are reliable, some complications can lead to serious maxillary sequelae, including the development of oro-antral fistula (OAF). Maxillary reconstruction in such patients presents a challenge owing to sinus floor alterations, graft remnants, chronic infection, and morbidity from the original sinus lift approach. The current study describes our technique of maxillary reconstruction using a Le Fort 1 approach following major sinus lift complications with associated residual OAF. This technique provides excellent access for sinus curettage, OAF closure, and osseous reconstruction. It allowed a successful rehabilitation in our patients, with no implant loss and good functional and esthetic results. PMID- 26825749 TI - Prognostic Implications of Lymph Node Yield in Central and Lateral Neck Dissections for Well-Differentiated Papillary Thyroid Carcinoma. AB - PURPOSE: The aim of this study was to evaluate the relationship between lymph node yield (LNY) from central (CND) and lateral (LND) neck dissections and risk of recurrence in patients undergoing primary surgery for well-differentiated papillary thyroid carcinoma (WDPTC). METHODS: Clinical data were reviewed from all patients with biopsy-proven WDPTC who underwent primary total thyroidectomy with CND or LND at the authors' institution from 2005 to 2009. Patient demographics and tumor characteristics were obtained, and clinical data with at least five-year follow-up were used. Within the CNDs and LNDs, total number of nodes removed (LNY), total positive nodes removed, and the ratio of positive lymph nodes to LNY were determined. RESULTS: One hundred fifty-two patients were included in the study, with average follow-up of 69 months. Of 125 patients who underwent CND, 20 had central neck disease recurrence. The LNY of patients with central neck recurrence was significantly less than those who had no recurrence (2.5 vs. 10.3; p < 0.0001). Of 71 patients who underwent LND, 23 had ipsilateral lateral neck disease recurrence. The LNY of patients with lateral neck recurrence was significantly less than those who did not recur (10.5 vs. 24.6; p < 0.0001). Higher rates of recurrence were associated with smaller LNY in both groups. For both groups, lower LNY remains predictive of recurrence on multivariate analysis controlling for pT stage, pN stage, American Joint Committee on Cancer stage, and radioactive iodine treatment. CONCLUSIONS: Higher LNY in CNDs and LNDs is associated with lower rates of papillary thyroid carcinoma recurrence in the central and lateral neck. To minimize the risk of recurrence and the need for secondary therapy with revision surgery and/or radiation, surgeons should perform thorough, compartment-oriented CNDs and LNDs when nodal surgery is undertaken. PMID- 26825751 TI - Gastrointestinal: Gastric mixed adenoneuroendocrine carcinoma. PMID- 26825750 TI - Single-locus enrichment without amplification for sequencing and direct detection of epigenetic modifications. AB - A gene-level targeted enrichment method for direct detection of epigenetic modifications is described. The approach is demonstrated on the CGG-repeat region of the FMR1 gene, for which large repeat expansions, hitherto refractory to sequencing, are known to cause fragile X syndrome. In addition to achieving a single-locus enrichment of nearly 700,000-fold, the elimination of all amplification steps removes PCR-induced bias in the repeat count and preserves the native epigenetic modifications of the DNA. In conjunction with the single molecule real-time sequencing approach, this enrichment method enables direct readout of the methylation status and the CGG repeat number of the FMR1 allele(s) for a clonally derived cell line. The current method avoids potential biases introduced through chemical modification and/or amplification methods for indirect detection of CpG methylation events. PMID- 26825752 TI - Gold(III) compounds-mediated inhibition of lung cancer cell proliferation. AB - Research on chemotherapeutics for lung cancer is crucial for designing a new therapeutic strategy against malignant lung tumors. Although radiotherapy and chemotherapy, which are not selective for cancer cells and exert toxic effects on healthy cells, have a limited advantage, they are the primary treatment modalities for non-small lung cancer. In addition to cytotoxicity, resistance of chemotherapeutics results in failure of treatment. This is why it is of utmost importance to focus on the creation of new chemotherapeutics without toxicity for the successful treatment and improved survival of cancer patients. New gold(III) and Pt(II) compounds were synthesized with a heterocyclic ligand using 2 phenylimidazo[4,5-f][1,10]phenanthroline as a ligand and bis-1,4-di[([1,10] phenanthroline-5-il)amino]-2-buten as a bridge molecule. The characterization of the compounds was carried out using a variety of spectroscopic methods (H NMR, IR, MS, and elemental analysis). Their antiproliferative, antitumoral, and apoptotic activities were determined. IR spectra and NMR results confirmed the formation of dinuclear heterocyclic complexes for two metal complexes. Cytotoxicity studies on lung cancer cells (A549) and healthy cells (CHL) showed a marked increase in cytotoxicity with the use of gold(III) complexes, and especially [Au(L)B](PF6)2 showed higher cytotoxic and apoptotic features than cisplatin at lower concentrations in cancer cells. These findings have been supported by results from DAPI staining and colorimetric measurement of the caspase-3 enzyme in both cell lines. Compounds showed selective toxicity on the cancer cells. In the light of the high efficacy of our newly synthesized gold complexes, they might be good and promising anticancer agents compared with cisplatin. PMID- 26825753 TI - The Strategy of Voluntary Certification in Italian Olive Oil Industry: Who and Why? AB - The phenomenon of asymmetric information is central in the agri-food sector, in which often there is not full information transparency about product quality. This condition is particularly complex considering the high-end products. In order to reduce this information gap, a company can choose voluntarily to participate in certification programs that can be viewed also as a simplification of some organization issues. The research aims to understand the characteristics of firms oriented to use voluntary certifications as a tool to reduce information asymmetries between producers and final consumers. In particular, we want to consider two contexts of analysis: a structural one, considering some specific internal aspects and investment choices of the firms; a second one that takes into account some decisions related to market relationships. The study concerns small and medium olive oil company of Southern Italy. The results show significant values in both the two dimensions considered. Among the first one, there are significances in immaterial company investments but also in physical assets related to the olive oil process. There are several scientific developments relevant to the olive oil process and some of these patents have been reviewed in this paper. In the second part of analysis there are significances in some distribution channels as well as in the export activity. This work aims to contribute to the debate about the addressing of quality policy for a reduction of asymmetric information in the high-end products. PMID- 26825754 TI - Consumer Behavior Under Conflicting Information Provided by Interested Parties: Implications for Equilibrium in the Market for Credence Goods. AB - BACKGROUND: Incomplete information in food consumption is a relevant topic in agricultural economics. This paper proposes a theoretical model describing consumer behavior, market equilibrium and public intervention in an industry where consumers must rely on the information of interested parties such as producers or associations. METHODS: We provide simple game theory model showing the link between price competition and the strategic use of information. If information are unverifiable (as in the case of credence attributes) firms may have no incentive to advertise true claims and consumer decisions may be biased. Our model incorporates the opportunistic behavior of self-interested information providers. RESULTS: The result is a model of competition in prices and information finding a potential for market failure and public intervention. In the paper we discuss the efficiency of three possible regulations: banning false claims, subsidizing advertising campaigns, and public statement if favor of true claims. CONCLUSION: In that context, some recent patents related to both the regulatory compliance in communication and to the reduction of asymmetric information between producers and consumers have been considered. Finally, we found that the efficiency of these policy tools is affected by the reputation of trustworthiness of the firms. PMID- 26825755 TI - Comparison of Prediction Rules and Clinician Suspicion for Identifying Children With Clinically Important Brain Injuries After Blunt Head Trauma. AB - OBJECTIVE: Children with minor head trauma frequently present to emergency departments (EDs). Identifying those with traumatic brain injuries (TBIs) can be difficult, and it is unknown whether clinical prediction rules outperform clinician suspicion. Our primary objective was to compare the test characteristics of the Pediatric Emergency Care Applied Research Network (PECARN) TBI prediction rules to clinician suspicion for identifying children with clinically important TBIs (ciTBIs) after minor blunt head trauma. Our secondary objective was to determine the reasons for obtaining computed tomography (CT) scans when clinical suspicion of ciTBI was low. METHODS: This was a planned secondary analysis of a previously conducted observational cohort study conducted in PECARN to derive and validate clinical prediction rules for ciTBI among children with minor blunt head trauma in 25 PECARN EDs. Clinicians recorded their suspicion of ciTBI before CT as <1, 1-5, 6-10, 11-50, or >50%. We defined ciTBI as 1) death from TBI, 2) neurosurgery, 3) intubation for more than 24 hours for TBI, or 4) hospital admission of 2 nights or more associated with TBI on CT. To avoid overfitting of the prediction rules, we performed comparisons of the prediction rules and clinician suspicion on the validation group only. On the validation group, we compared the test accuracies of clinician suspicion > 1% versus having at least one predictor in the PECARN TBI age-specific prediction rules for identifying children with ciTBIs (one rule for children <2 years [preverbal], the other rule for children >2 years [verbal]). RESULTS: In the parent study, we enrolled 8,627 children to validate the prediction rules, after enrolling 33,785 children to derive the prediction rules. In the validation group, clinician suspicion of ciTBI was recorded in 8,496/8,627 (98.5%) patients, and 87 (1.0%) had ciTBIs. CT scans were obtained in 2,857 (33.6%) patients in the validation group for whom clinician suspicion of ciTBI was recorded, including 2,099/7,688 (27.3%) of those with clinician suspicion of ciTBI of <1% and 758/808 (93.8%) of those with clinician suspicion >1%. The PECARN prediction rules were significantly more sensitive than clinician suspicion >1% of ciTBI for preverbal (100% [95% confidence interval {CI} = 86.3% to 100%] vs. 60.0% [95% CI = 38.7% to 78.9%]) and verbal children (96.8% [95% CI = 88.8% to 99.6%] vs. 64.5% [95% CI = 51.3% to 76.3%]). Prediction rule specificity, however, was lower than clinician suspicion >1% for preverbal children (53.6% [95% CI = 51.5% to 55.7%] vs. 92.4% [95% CI = 91.2% to 93.5%]) and verbal children (58.2% [95% CI = 56.9% to 59.4%] vs. 90.6% [95% CI = 89.8% to 91.3%]). Of the 7,688 patients in the validation group with clinician suspicion recorded as <1%, CTs were nevertheless obtained in 2,099 (27.3%). Three of 16 (18.8%) patients undergoing neurosurgery had clinician suspicion of ciTBI <1%. CONCLUSIONS: The PECARN TBI prediction rules had substantially greater sensitivity, but lower specificity, than clinician suspicion of ciTBI for children with minor blunt head trauma. Because CT ordering did not follow clinician suspicion of <1%, these prediction rules can augment clinician judgment and help obviate CT ordering for children at very low risk of ciTBI. PMID- 26825756 TI - Quasi experimental designs in pharmacist intervention research. AB - Background In the field of pharmacist intervention research it is often difficult to conform to the rigorous requirements of the "true experimental" models, especially the requirement of randomization. When randomization is not feasible, a practice based researcher can choose from a range of "quasi-experimental designs" i.e., non-randomised and at time non controlled. Objective The aim of this article was to provide an overview of quasi-experimental designs, discuss their strengths and weaknesses and to investigate their application in pharmacist intervention research over the previous decade. Results In the literature quasi experimental studies may be classified into five broad categories: quasi experimental design without control groups; quasi-experimental design that use control groups with no pre-test; quasi-experimental design that use control groups and pre-tests; interrupted time series and stepped wedge designs. Quasi experimental study design has consistently featured in the evolution of pharmacist intervention research. The most commonly applied of all quasi experimental designs in the practice based research literature are the one group pre-post-test design and the non-equivalent control group design i.e., (untreated control group with dependent pre-tests and post-tests) and have been used to test the impact of pharmacist interventions in general medications management as well as in specific disease states. Conclusion Quasi experimental studies have a role to play as proof of concept, in the pilot phases of interventions when testing different intervention components, especially in complex interventions. They serve to develop an understanding of possible intervention effects: while in isolation they yield weak evidence of clinical efficacy, taken collectively, they help build a body of evidence in support of the value of pharmacist interventions across different practice settings and countries. However, when a traditional RCT is not feasible for logistical and/or ethical reasons researchers should endeavour to use the more robust of the quasi experimental designs. PMID- 26825757 TI - Efficacy of partially hydrolyzed guar gum (PHGG) supplemented modified oral rehydration solution in the treatment of severely malnourished children with watery diarrhoea: a randomised double-blind controlled trial. AB - OBJECTIVES: To examine whether PHGG added ORS reduce duration of diarrhoea, stool output and enhance weight gain. METHODS: In a double-blind controlled clinical trial, 126 malnourished children (weight for length/weight for age < -3 Z-score with or without pedal edema), aged 6 - 36 months with acute diarrhoea <7 days were studied in two treatment groups; 63 received modified WHO ORS (Na 75, K 40, Cl 87, citrate 7, glucose 90 mmol/L) with PHGG 15 g/L (study group); 63 received modified WHO ORS without PHGG (control). Other treatments were similar in both groups. The study protocol was approved by Ethics Committee of icddr,b; the study was carried out at the Dhaka Hospital. RESULTS: The mean duration of diarrhoea (h) was significantly shorter in children of the study group (Study vs. control, mean +/- SD, 57 +/- 31 vs. 75 +/- 39, p = 0.01). Although there was a trend in stool weight reduction in children receiving ORS with PHGG (study vs. control, stool weight (g), mean +/- SD; 1(st) 24 hour, 854.03 +/- 532.15 vs. 949.11 +/- 544.33, p = 0.32; 2(nd) 24 hour, 579.84 +/- 466.01 vs. 761.26 +/- 631.64, p = 0.069; 3(rd) 24 hour, 385.87 +/- 454.09 vs. 495.73 +/- 487.61, p = 0.196), especially in 2(nd) 24 h period, the difference was not statistically significant. The mean time (day) to attain weight for length 80% of NCHS median without edema was significantly shorter in the study group (study vs. control, mean +/- SD, 4.5 +/- 2.6 vs. 5.7 +/- 2.8, p = 0.027). CONCLUSION: PHGG added to ORS substantially reduced duration of diarrhoea. It also enhanced weight gain. Further studies might substantiate to establish its beneficial effect. CLINICAL TRIAL REGISTRATION NUMBER: NCT01821586. PMID- 26825758 TI - Orthostatic hypotension and the risk of incidental cardiovascular diseases: A meta-analysis of prospective cohort studies. AB - OBJECTIVE: To quantitatively estimate the prospective associations between orthostatic hypotension (OH) and cardiovascular diseases, including coronary heart disease (CHD) and stroke. METHODS: Relevant prospective cohort studies were identified by searching of Medline and Embase databases. We applied fixed or random effect model to estimate the overall effects depending on the heterogeneity among the included studies. RESULTS: Eight published articles from 7 cohorts, consisting of 64,782 participants, were included. During a mean follow up of 15.2years, 5719 CHD events and 3657 stroke events occurred. The overall results of the meta-analysis indicated that OH was associated with significant increased risk for incident CHD (adjusted hazard ratio [HR]: 1.32, 95% confidence interval [CI]: 1.12-1.56) and stroke (HR: 1.19, 95% CI 1.08-1.30), which were independent of conventional risk factors. Stratified analyses by ages suggested that the associations between OH and CHD and stroke were significant for both the middle-aged and the old participants. CONCLUSION: Presence of OH was independently related to significantly increased risk for incidence of CHD and stroke. Further, studies regarding the mechanisms and potential treatments for OH may be important for understanding whether the associations between OH and cardiovascular diseases are causative. PMID- 26825759 TI - Depressive symptomatology in relation to 10-year (2004-2014) acute coronary syndrome incidence; the moderating role of diet and financial status. AB - BACKGROUND: The association between depression status and 10-year cardiovascular disease (CVD) incidence among acute coronary syndrome (ACS) patients, in relation to nutritional and financial status, was evaluated. METHODS: From October 2003 to September 2004, a sample of 2172 consecutive ACS patients from 6 Greek hospitals was enrolled. In 2013-14, the 10-year follow-up was performed. Depressive symptoms were evaluated using the validated CES-D score (range 0-60). Adherence to Mediterranean diet was assessed through MedDietScore (range 0-55) and financial status was determined by the annual income. RESULTS: Ranking from the 1st to 3rd CES-D tertile, recurrent fatal/non fatal ACS rates were 33%, 37% and 42%, respectively (p=0.006). Multiple logistic regression models revealed an adverse association of severe depression status (i.e. 3rd tertile) compared to no depression (i.e. 1st tertile) [odds ratio (OR)=1.31, 95% confidence interval (95% CI) 1.01, 1.69]. When controlling for financial status, the relationship between depression and ACS prognosis remained marginally significant; while subgroup analysis revealed that only patients with low/moderate income were negatively affected [OR=1.36, 95% CI 0.98, 1.88]. Further stratified analysis, by MedDietScore group, was applied; the above association remained significant only in patients with low compliance to this dietary pattern [OR=1.68, 95% CI 1.10, 2.18]. CONCLUSIONS: ACS coexisting with severe depression status seems to result in adverse disease outcomes while financial status and Mediterranean diet are proposed as potential moderators. Public health programs should focus on vulnerable groups and minimize depressive symptoms through appropriate medical treatment and lifestyle interventions, so as to ameliorate the disease prognosis in clinical and community levels. PMID- 26825760 TI - A sequential logit model of caretakers' decision to vaccinate children for the human papillomavirus virus in the general population. AB - OBJECTIVES: This study explores the predisposing, enabling, and need-based factors associated with parents' or guardians' decision to have their child initiate, continue, and complete the human papillomavirus (HPV) vaccine. METHODS: Parents and guardians of children between the ages of 9 and 17years who completed the 2010 Behavioral Risk Factor Surveillance System survey collected by the Center for Disease Control (CDC, 2010) were analyzed. Utilizing Andersen's health care beliefs model, we explored the sequential nature of the decision to vaccinate (i.e., the decision to receive the first, second, and third dose), thereby allowing the independent variables to vary across each transition. RESULTS: Among all children, 3.7% received exactly 1 shot, 16.3% received at least one shot, and 8.9% received all three shots. Among those who received at least one shot, 22.4% received exactly one shot, 23.7% received exactly 2 shots, and 54.9% completed all 3 shots. A differential impact was observed across transitions. Predisposing factors, such as being Hispanic (OR=1.9) and child age (OR=1.4), significantly predicted the decision to receive the first dose but enabling factors, such as having a regular physician (OR=4.5) and income (OR=.74) were more important for predicting completion. CONCLUSIONS: The decision to initiate and complete HPV vaccination depends on a specific mix of enabling, predisposing, and need-based factors. Our analysis underscores the importance of modeling the vaccination decision in a manner that is consistent with how primary caregivers navigate real-life health care decisions for their children. PMID- 26825761 TI - Preventing dementia by promoting physical activity and the long-term impact on health and social care expenditures. AB - BACKGROUND: Preventing dementia has been proposed to increase population health as well as reduce the demand for health and social care. Our aim was to evaluate whether preventing dementia by promoting physical activity (PA) a) improves population health or b) reduces expenditure for both health and social care if one takes into account the additional demand in health and social care caused by increased life expectancy. METHODS: A simulation model was developed that models the relation between PA, dementia, mortality, and the use of health care and social care in England. With this model, scenarios were evaluated in which different assumptions were made about the increase in PA level in (part of) the population. RESULTS: Lifetime spending on health and social care related to dementia was highest for the physically inactive (L28,100/L28,900 for 40-year-old males/females), but spending on other diseases was highest for those that meet PA recommendations (L55,200/L43,300 for 40-year-old males/females) due to their longer life expectancies. If the English population aged 40-65 were to increase their PA by one level, life expectancy would increase by 0.23years and health and social care expenditures would decrease by L400 per person. CONCLUSIONS: Preventing dementia by increasing PA increases life expectancy and can result in decreased spending overall on health and social care, even after additional spending during life years gained has been taken into account. If prevention is targeted at the physically inactive, savings in dementia-related costs outweigh the additional spending in life years gained. PMID- 26825762 TI - Carotid Intima Media Thickness and Its Utility as a Predictor of Cardiovascular Disease: A Review of Evidence. AB - Cardiovascular (CV) disease is still the leading cause of death in the developed world, despite the considerable progress in CV medical and surgical therapeutics. Many risk factors are associated with the development of future adverse CV events, such as age, hypertension, body mass index, and other comorbidities. Carotid intima media thickness (CIMT) is one method of calculating plaque burden by assessing the level of arterial thickening present. CIMT can be used as a noninvasive marker of atherosclerotic disease with increasing CIMT linked to an increased risk of subsequent CV events. In this review, the association of CIMT with CV disease is explored. Current literature on the role of CIMT in predicting CV outcomes is reviewed to determine whether it is a predictor of CV events, both in the general population and in the high-risk groups, such as those with hypertension, diabetes mellitus, and chronic kidney disease. PMID- 26825763 TI - Steroid Limbo in Acute Severe Ulcerative Colitis: How Low Can You Go? PMID- 26825764 TI - Omega-3 Fatty Acid-Rich Parenteral Nutrition: Is It a Double-Edged Sword? PMID- 26825765 TI - Peginterferon Therapy in Children With Chronic Hepatitis C: A Nationwide, Multicenter Study in Japan, 2004-2013. AB - OBJECTIVES: The aim of the present study was to review the medical treatment of Japanese children and adolescents with chronic hepatitis C in the past 10 years. METHODS: This nationwide, multicenter study evaluated patients who were younger than 18 years of age when diagnosed with chronic hepatitis C virus (HCV) infection and were treated with pegylated interferon (PEG-IFN) monotherapy or PEG IFN/ribavirin (RBV) combination therapy between 2004 and 2013. The subjects' median age was 10 (3-18) years, with a male to female ratio of 52:50 and a genotype-1 to genotype-2 ratio of 45:57. Among the 102 patients, 18 received PEG IFN monotherapy and 84 received PEG-IFN/RBV combination therapy. The IL28B genotype polymorphism was analyzed in patients infected with genotype-1. RESULTS: In patients with HCV genotype-1 infections, sustained virological response (SVR) rates obtained by PEG-IFN monotherapy and by PEG-IFN/RBV combination therapy were 100% (2/2) and 72% (31/43), respectively. In patients with HCV genotype-2 infections, SVRs were 75% (12/16) and 100% (41/41), respectively. In 32 genotype 1 patients available for the IL28B genotype (rs8099917), SVR was achieved in more patients in the IL28B major allele group than in the minor allele group (15/17 vs 7/15, P = 0.021) after PEG-IFN/RBV combination therapy. The frequencies of adverse events were similar between the treatment regimens. CONCLUSIONS: Overall, both therapies showed encouraging results, and were reasonably safe in children and adolescents with chronic hepatitis C. The IL28B genotype was useful for predicting the treatment response to PEG-IFN/RBV combination therapy in this cohort. PMID- 26825767 TI - Serial Balloon Dilation to Relieve Gastric Outlet Obstruction Induced by the Ingestion of Toilet Cleaner. PMID- 26825766 TI - ESPGHAN Committee on Nutrition Position Paper. Intravenous Lipid Emulsions and Risk of Hepatotoxicity in Infants and Children: a Systematic Review and Meta analysis. AB - The aim of the present article was to perform a systematic review with meta analysis of available scientific evidence regarding the role of different intravenous lipid emulsions (ILE) in the pathogenesis of cholestasis and parenteral nutrition-associated liver disease. A systematic review of the literature (up to March 2015) identified 23 randomized controlled trials (RCTs). Of these, 17 were performed in preterm infants or critically ill neonates with a short duration of intervention, 2 in older children with short-term use (following surgery or bone marrow transplantation), 1 in neonates with long-term use, and 3 in infants and children receiving long-term parenteral nutrition (PN). Meta-analysis showed no differences in the rate of cholestasis or bilirubin levels associated with short-term use of different ILEs. Because of high heterogeneity of the long-term studies no meta-analysis could be performed. Available studies found that the use of multicomponent fish oil (FO)-containing ILE compared with pure soya bean oil (SO), ILE-reduced liver enzymes, and bilirubin levels in noncholestatic children on long-term PN and one other RCT found that FO-based ILE-reversed cholestasis in a proportion of patients. The ESPGHAN Committee on Nutrition concludes that there is no evidence of a difference in rates of cholestasis or bilirubin levels between different ILE for short-term use in neonates. The use of multicomponent FO-containing ILE may contribute to a decrease in total bilirubin levels in children with IF on prolonged PN. Well-designed RCTs are, however, lacking and long-term effects have not been determined. PMID- 26825768 TI - Clinical Characteristics and Prognosis in Children and Adolescents With Autoimmune Hepatitis and Overlap Syndrome. AB - OBJECTIVES: This is a cohort study of 134 children and adolescents with a known diagnosis of autoimmune hepatitis (AIH). During follow-up, some of them developed autoimmune sclerosing cholangitis (ASC). This study describes the characteristics of the patients upon diagnosis, and their response to treatment and any complications, and compares the patients who developed ASC during follow-up (ASC group) with those who did not (AIH group). METHODS: A total of 73.1% of the patients were girls with a median age upon diagnosis of 10.41 (7.41-12.53) years. RESULTS: Of 134 patients, 28 (20.9%) developed cholestatic manifestations, with features of ASC. A few differences were observed between the AIH and ASC groups when they were analyzed by chi test, such as the smaller predominance of girls in ASC group (P = 0.04), and more common asymptomatic presentation in the ASC group (P = 0.01). Cirrhosis was observed in 68% of biopsies, with no significant difference between groups (P = 0.43). Of 16 deaths, 15 were in the AIH group and 1 in the ASC group (P = 0.22). Of 11 transplants, 10 were in the AIH group and one in the ASC group (P = 0.53). The presence of cirrhosis at baseline was associated with a smaller survival probability (P = 0.015). The survival rate by Kaplan-Meier method was 94% at 5 years and 80% at 10 years, and was similar in both the groups (P = 0.08). CONCLUSIONS: No statistically significant difference was observed between the groups in relation to prognosis and response to treatment. PMID- 26825769 TI - Vitamin D Intake in Very Low Birth Weight Infants in Neonatal Intensive Care Unit. AB - It is unknown how often preterm infants in neonatal intensive care units achieve the American Academy of Pediatrics-recommended daily intake of 400 international units of Vitamin D. We studied 378 preterm infants with birth weight 1500 g or less admitted to our neonatal intensive care unit, 151 infants before and 227 infants after daily vitamin D-intake monitoring was introduced. Infants were stratified into 2 groups: extremely low birth weight (<1000 g) and Very low birth weight (1000-1500 g). Monitoring of daily intake coincided with significant improvement in vitamin D intake in both extremely low birth weight and very low birth weight groups. PMID- 26825770 TI - Intact Regulatory T-Cell Function but Defective Generation of IL-17A-Producing CD4+ T Cells in XIAP Deficiency. AB - OBJECTIVE: X-linked inhibitor of apoptosis (xIAP) deficiency is a primary immune deficiency disorder associated with hemophagocytic lymphohistiocytosis. About 17% of xIAP-deficient patients present with very early onset severe colitis with high mortality. We hypothesized that xIAP deficiency leads to defective generation and/or survival of T regulatory cells (Treg) through its involvement in transforming growth factor-beta signaling. METHODS AND RESULTS: We used a T-cell transfer model of chronic colitis and observed a mild increase in colitis severity induced by naive CD4 T cells from xIAP mice compared with colitis induced by naive CD4 T cells from WT mice. We did not observe any significant difference in the induction of Treg cells in these studies. We next tested whether xIAP is required for Treg cell function by co-transferring xIAP or WT Treg cells with naive WT CD4 cells in this model. We demonstrate that XIAP deficient Treg cells were able to prevent disease similarly to WT Treg cells. In these experiments we, however, found a significantly decreased percentage of IL 17A-producing CD4 T cells in mice receiving Tregs from xIAP mice. CONCLUSIONS: xIAP appears dispensable for the generation of induced Treg cells as well as function of natural Treg cells. There appeared to be a role of xIAP in generation of IL-17-producing cells from either naive CD4 T cells or Treg cells. Further research is needed to explore the role of xIAP in generation of IL-17-producing cells. PMID- 26825771 TI - Characterisation of two self-sufficient CYP102 family monooxygenases from Ktedonobacter racemifer DSM44963 which have new fatty acid alcohol product profiles. AB - BACKGROUND: Two self-sufficient CYP102 family encoding genes (Krac_0936 and Krac_9955) from the bacterium Ktedonobacter racemifer DSM44963, which possesses one of the largest bacterial genomes, have been identified. METHODS: Phylogenetic analysis of both the encoded cytochrome P450 enzymes, Krac0936 and Krac9955. Both enzymes were produced and their turnovers with fatty acid substrates assessed in vitro and using a whole-cell oxidation system. RESULTS: Krac0936 hydroxylated straight chain, saturated fatty acids predominantly at the omega-1 and omega-2 positions using NADPH as the cofactor. Krac0936 was less active towards shorter unsaturated fatty acids but longer unsaturated acids were efficiently oxidised. cis,cis-9,12-Octadecadienoic and pentadecanoic acids were the most active substrates tested with Krac0936. Unusually Krac9955 showed very low levels of NAD(P)H oxidation activity though coupling of the reducing equivalents to product formation was high. The product distribution of tridecanoic, tetradecanoic and pentadecanoic acid oxidation by Krac9955 favoured oxidation at the omega-4, omega 5 and omega-6 positions, respectively. CONCLUSION: Krac0936 and Krac9955 are self sufficient P450 monooxygenases. Krac0936 has a preference for pentadecanoic acid over other straight chain fatty acids and showed little or no activity with dodecanoic or octadecanoic acids. Krac9955 preferably oxidised shorter fatty acids compared to Krac0936 with tridecanoic having the highest levels of product formation. Unlike Krac0936 and P450Bm3, Krac9995 showed lower activities with unsaturated fatty acids. GENERAL SIGNIFICANCE: In this study of two of the CYP enzymes from K. racemifer we have shown that this bacterium from the Chloroflexi phylum contains genes which encode new proteins with novel activity. PMID- 26825772 TI - Pectin-coated boron nitride nanotubes: In vitro cyto-/immune-compatibility on RAW 264.7 macrophages. AB - BACKGROUND: Boron nitride nanotubes (BNNTs) represent a new opportunity for drug delivery and clinical therapy. The present work has the objective to investigate pectin-coated BNNTs (P-BNNTs) for their biocompatibility on macrophage cultures, since these cells are among the first components of the immune system to interact with administered nanoparticles. METHODS: As first step, the potential toxicity of P-BNNTs is verified in terms of proliferation, oxidative stress induction and apoptosis/necrosis phenomena. Thereafter, the modulation of immune cell response following P-BNNT exposure is evaluated at gene and protein level, in particular focusing on cytokine release. Finally, P-BNNT internalization is assessed through transmission electron microscopy and confocal microscopy. RESULTS: The results proved that P-BNNTs are not toxic for macrophages up to 50 MUg/ml after 24 h of incubation. The cytokine expression is not affected by P-BNNT administration both at gene and protein level. Moreover, P-BNNTs are internalized by macrophages without impairments of the cell structures. CONCLUSIONS: Collected data suggest that P-BNNTs cause neither adverse effects nor inflammation processes in macrophages. GENERAL SIGNIFICANCE: These findings represent the first and fundamental step in immune compatibility evaluation of BNNTs, mandatory before any further pre-clinical testing. PMID- 26825774 TI - Receptor for hyaluronic acid- mediated motility (RHAMM) regulates HT1080 fibrosarcoma cell proliferation via a beta-catenin/c-myc signaling axis. AB - BACKGROUND: High levels of hyaluronan (HA) synthesis in various cancer tissues, including sarcomas, are correlated with tumorigenesis and malignant transformation. RHAMM (receptor for hyaluronic acid-mediated motility) is overexpressed during tumor development in different malignancies. beta-Catenin is a crucial downstream mediator of the Wnt signaling cascade which facilitates carcinogenic events characterized by deregulated cell proliferation. METHODS: Real-time PCR, in vitro cell proliferation assay, siRNA transfection, flow cytometry, immunoprecipitation, western blotting and immunofluorescence were utilized. RESULTS: The reduction of RHAMM expression was strongly correlated with an inhibition of HT1080 fibrosarcoma cell growth (p<=0.01). LMWHA, in a RHAMM dependent manner increases cell growth of HT1080 cells (p<=0.01). Both basal and LMWHA dependent growth of HT1080 cells was attenuated by beta-catenin deficiency (p<=0.01). beta-Catenin cytoplasmatic deposition is positively regulated by RHAMM (p<=0.01). Immunoflourescence and immunoprecipitation suggest that RHAMM/beta catenin form an intracellular complex. Transfection experiments identified c-myc as candidate downstream mediator of RHAMM/beta-catenin effects on HT1080 fibrosarcoma cell proliferation. CONCLUSIONS: LMWHA/RHAMM downstream signaling regulates fibrosarcoma cell growth in a beta-catenin/c-myc dependent manner. GENERAL SIGNIFICANCE: The present study suggests that RHAMM is a novel beta catenin intracellular binding partner, protecting beta-catenin from degradation and supporting the nuclear translocation of this key cellular mediator, which results in c-myc activation and enhanced fibrosarcoma cell growth. PMID- 26825773 TI - Glutamine drives glutathione synthesis and contributes to radiation sensitivity of A549 and H460 lung cancer cell lines. AB - BACKGROUND: Increased glutamine uptake is known to drive cancer cell proliferation, making tumor cells glutamine-dependent. Glutamine provides additional carbon and nitrogen sources for cell growth. The first step in glutamine utilization is its conversion to glutamate by glutaminase (GLS). Glutamate is a precursor for glutathione synthesis, and we investigated the hypothesis that glutamine drives glutathione synthesis and thereby contributes to cellular defense systems. METHODS: The importance of glutamine for glutathione synthesis was studied in H460 and A549 lung cancer cell lines using glutamine free medium and bis-2-(5-phenyl-acetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) a GLS inhibitor. Metabolic activities were determined by targeted mass spectrometry. RESULTS: A significant correlation between glutamine consumption and glutathione excretion was demonstrated in H460 and A549 tumor cells. Culturing in the presence of [(13)C5]glutamine demonstrated that by 12h >50% of excreted glutathione was derived from glutamine. Culturing in glutamine-free medium or treatment with BPTES, a GLS-specific inhibitor, reduced cell proliferation and viability and abolished glutathione excretion. Treatment with glutathione-ester prevented BPTES-induced cytotoxicity. Inhibition of GLS markedly radiosensitized the lung tumor cell lines, suggesting an important role of glutamine-derived glutathione in determining radiation sensitivity. CONCLUSIONS: We demonstrate here for the first time that a significant amount of extracellular glutathione is directly derived from glutamine. This finding adds yet another important function to the already known glutamine dependence of tumor cells and probably tumors as well. GENERAL SIGNIFICANCE: Glutamine is essential for synthesis and excretion of glutathione to promote cell growth and viability. PMID- 26825775 TI - A new oxygen modification cyclooctaoxygen binds to nucleic acids as sodium crown complex. AB - BACKGROUND: Oxygen exists in two gaseous and six solid allotropic modifications. An additional allotropic modification of oxygen, the cyclooctaoxygen, was predicted to exist in 1990. METHODS: Cyclooctaoxygen sodium was synthesized in vitro from atmospheric oxygen, or catalase effect-generated oxygen, under catalysis of cytosine nucleosides and either ninhydrin or eukaryotic low molecular weight RNA. Thin-layer chromatographic mobility shift assays were applied on specific nucleic acids and the cyclooctaoxygen sodium complex. RESULTS: We report the first synthesis and characterization of cyclooctaoxygen as its sodium crown complex, isolated in the form of three cytosine nucleoside hydrochloride complexes. The cationic cyclooctaoxygen sodium complex is shown to bind to nucleic acids (RNA and DNA), to associate with single-stranded DNA and spermine phosphate, and to be essentially non-toxic to cultured mammalian cells at 0.1-1.0mM concentration. CONCLUSIONS: We postulate that cyclooctaoxygen is formed in most eukaryotic cells in vivo from dihydrogen peroxide in a catalase reaction catalyzed by cytidine and RNA. A molecular biological model is deduced for a first epigenetic shell of eukaryotic in vivo DNA. This model incorporates an epigenetic explanation for the interactions of the essential micronutrient selenium (as selenite) with eukaryotic in vivo DNA. GENERAL SIGNIFICANCE: Since the sperminium phosphate/cyclooctaoxygen sodium complex is calculated to cover the active regions (2.6%) of bovine lymphocyte interphase genome, and 12.4% of murine enterocyte mitotic chromatin, we propose that the sperminium phosphate/cyclooctaoxygen sodium complex coverage of nucleic acids is essential to eukaryotic gene regulation and promoted proto-eukaryotic evolution. PMID- 26825776 TI - Cerebral 5-HT release correlates with [11C]Cimbi36 PET measures of 5-HT2A receptor occupancy in the pig brain. AB - Positron emission tomography (PET) can, when used with appropriate radioligands, non-invasively generate temporal and spatial information about acute changes in brain neurotransmitter systems. We for the first time evaluate the novel 5-HT2A receptor agonist PET radioligand, [11C]Cimbi-36, for its sensitivity to detect changes in endogenous cerebral 5-HT levels, as induced by different pharmacological challenges. To enable a direct translation of PET imaging data to changes in brain 5-HT levels, we calibrated the [11C]Cimbi-36 PET signal in the pig brain by simultaneous measurements of extracellular 5-HT levels with microdialysis and [11C]Cimbi-36 PET after various acute interventions (saline, citalopram, citalopram + pindolol, fenfluramine). In a subset of pigs, para chlorophenylalanine pretreatment was given to deplete cerebral 5-HT. The interventions increased the cerebral extracellular 5-HT levels to 2-11 times baseline, with fenfluramine being the most potent pharmacological enhancer of 5 HT release, and induced a varying degree of decline in [11C]Cimbi-36 binding in the brain, consistent with the occupancy competition model. The observed correlation between changes in the extracellular 5-HT level in the pig brain and the 5-HT2A receptor occupancy indicates that [11C]Cimbi-36 binding is sensitive to changes in endogenous 5-HT levels, although only detectable with PET when the 5-HT release is sufficiently high. PMID- 26825778 TI - Sports Eligibility After Risk Assessment and Treatment in Children with Asymptomatic Ventricular Pre-excitation. AB - BACKGROUND AND OBJECTIVE: Many studies concern the management of young patients with symptomatic Wolff-Parkinson-White (WPW) syndrome, but little information exists on the significance and prognosis of ventricular pre-excitation (VPE) in asymptomatic children. The aim of the study was to evaluate the risk of sudden death in young athletes with asymptomatic VPE by transesophageal electrophysiological study (TEEPS) and their sports eligibility after the risk assessment and/or ablative treatment. METHODS: Ninety-one asymptomatic children and adolescents underwent TEEPS both at rest and during adrenergic stress (exercise testing or isoproterenol infusion). After electrophysiological testing, patients were assessed in the 36 months of follow-up. RESULTS: Thirty-three patients (36.3 %) had a benign form of VPE and were allowed to participate in competitions. Ten patients (11 %) were at borderline risk; thus, sport eligibility was evaluated individually. Forty-eight patients (52.7 %) showed inducible sustained atrioventricular reentrant tachycardia and/or atrial fibrillation (AF), 11 of whom (12.1 % of total population) had a potential risk of sudden cardiac death due to AF inducibility during physical stress. Forty-five young athletes underwent transcatheter ablation (TCA). TCA was interrupted in 12 patients (26.7 %) because of the high procedural risk linked to septal accessory pathway (AP) location. There were no TCA-related complications, and all patients remained asymptomatic during follow-up. CONCLUSION: Most of the young athletes with asymptomatic VPE may be allowed to participate in competitive sports after an adequate risk assessment and/or ablative treatment. However, in our opinion, special care should be taken to avoid procedural complications, which are unacceptable in asymptomatic patients. PMID- 26825779 TI - From genomic medicine to precision medicine: highlights of 2015. PMID- 26825777 TI - Impact of men's dairy intake on assisted reproductive technology outcomes among couples attending a fertility clinic. AB - Intake of full-fat dairy has been linked to lower semen quality but whether this leads to decreased fertility is unknown. To address this question, we prospectively evaluated the association of men's dairy intake with treatment outcomes of subfertile couples undergoing assisted reproductive technology (ART). We followed 142 men from couples undergoing infertility treatment with ART at an academic fertility centre between 2007 and 2014. Couples completed dietary assessments prior to treatment, and the female partners underwent a total of 248 ART cycles. Multivariable generalized linear mixed models were used to examine the association of dairy intake with fertilization, implantation, clinical pregnancy and live birth rates adjusting for age, body mass index, smoking status, total exercise time, dietary patterns, alcohol, caffeine, total energy intake, and female dairy intake. Intake of dairy foods, regardless of their fat content, was not associated with fertilization, implantation, clinical pregnancy or live birth rates. The adjusted live birth rates (95% confidence interval) for couples in increasing quartiles of men's dairy intake were 0.42 (0.25, 0.60), 0.25 (0.13, 0.42), 0.26 (0.15, 0.41), and 0.44 (0.27, 0.63) (p linear trend = 0.73). Results remained similar after adjustment for female partner intake of dairy foods. Overall, men's dairy intake was not associated with treatment outcomes of couples undergoing ART. PMID- 26825780 TI - Clinical DRUJ instability does not influence the long-term functional outcome of conservatively treated distal radius fractures. AB - OBJECTIVE: The presence of distal radioulnar joint (DRUJ) instability remains often unnoticed initially, but may worsen functional outcome of distal radius fractures (DRF). The aim of this study was to evaluate the influence of concurring clinical DRUJ instability on the outcome of conservatively treated DRF. METHODS: In a retrospective cohort study, all unilateral, conservatively treated DRF patients were invited for physical examination, CT scan of both wrists and filling out questionnaires. Static and dynamic DRUJ instability were clinically tested. RESULTS: Forty-nine DRF patients with a mean follow-up of 4.2 years (SD 0.5) were assessed. Seventeen patients tested positive for DRUJ instability. No differences were found in baseline characteristics between the DRUJ stable and unstable group. Apart from wrist flexion, no statistical significant differences in outcome was found between patients with and without DRUJ instability. CONCLUSION: The presence of clinical DRUJ instability does not seem to affect functional outcome of conservatively treated distal radius fractures at long-term follow-up. PMID- 26825781 TI - Acylated neo-clerodane type diterpenoids from the aerial parts of Scutellaria coleifolia Levl. (Lamiaceae). AB - Twenty new neo-clerodane type diterpenoids, scutefolides G1-S (1-20), were isolated from the 70 % aqueous acetone extract of the aerial parts of Scutellaria coleifolia. Their structures were elucidated by extensive spectroscopic analyses. The absolute configurations of 1, 2, 7, 8, 14 and 15 were determined by means of the CD exciton chirality method. Compounds 1, 2, 5, 7, 8, 12, 14, 15, 18 and 19 were evaluated for their cytotoxic activities against four human cancer cell lines, and anti-bacterial activities against methicillin-resistant Staphylococcus aureus. PMID- 26825782 TI - Residues and Distribution of Organochlorine Pesticides in Water and Suspended Particulate Matter from Hangzhou Bay, East China Sea. AB - The concentrations, distribution, and possible sources of organochlorine pesticides (OCPs) in Hangzhou Bay, East China Sea, were studied by analyzing water column and suspended particulate matter (SPM) samples from 13 sites. The results showed that OCP contamination remains widespread in the area. The OCP concentrations were 2.52-27.99 ng/L in the SPM samples and 1.35-26.36 ng/L in the water column samples. Pattern analysis suggested that both fresh and weathered hexachlorocyclohexane (HCH) were present. Low alpha-HCH/gamma-HCH ratios and high beta-HCH and gamma-HCH levels contributed to the total HCH concentrations in both the water column and SPM samples. High p,p'-dichlorodiphenyltrichloroethane (DDT)/o,p'-DDT ratios and low (dichlorodiphenyldichloroethylene + dichlorodiphenyldichloroethane)/DDT ratios were found, reflecting a "dicofol type" DDT input pattern, This suggested that new DDT inputs are occurring because of dicofol still being used in the area. PMID- 26825783 TI - Use of modified lateral upper arm free flap for reconstruction of soft tissue defect after resection of oral cancer. AB - BACKGROUND: To evaluate the suitability of a modified lateral upper arm free flap (LAFF) for reconstruction of soft tissue defects after resection of oral cancer. METHODS: Eighteen cases of soft tissue defect repair performed between January 2011 and December 2013 using a modified LAFF after resection of oral cancer were reviewed. The design and harvest of the LAFF, the reconstruction procedure, and postoperative morbidity were reviewed and evaluated over a follow-up period of at least 12 months. RESULTS: The overall flap survival was 94.4 % (17/18 patients). A broad scar at the donor site was the most common morbidity, but patients did not report dissatisfaction with the scar because they could easily cover it. All wounds at the donor site achieved primary recovery. One case of flap loss was repaired with a radial forearm free flap. One case complicated by diabetes mellitus involved infection of the flap with one-third of the flap becoming necrotic. This flap survived after removal of the necrotic tissue. In one other case, fat liquefactive necrosis (1.5 * 1.0 cm) occurred in the flap on the tip of the tongue, and this flap survived after debridement. Overall, the shape and function of the reconstructed tissues were well restored, and there was no severe morbidity at the donor site in any case. CONCLUSION: The modified LAFF was safe and reliable for the reconstruction of soft tissue defects after resection of oral cancer. PMID- 26825784 TI - Evidence of Helicobacter spp. in freshwaters from Roraima Tepui, Guayana Shield, South America. AB - Helicobacter presence and viability in waters is not well characterized. The identification of natural reservoirs and infection sources may provide novel insights into its waterborne transmission. The goal of this study was to investigated the occurrence of Helicobacter spp. in natural freshwaters from Roraima Tepui, a little studied and unique ecosystem of the Guayana Shield. Freshwaters collected from two localities at Roraima Tepui were cultured in HP selective broth and agar for Helicobacter pylori and analysed by fluorescent in situ hybridization (FISH), specific PCR assays, 16S rRNA gene sequencing and phylogenetic analysis. The presence of other bacteria in freshwater enrichments was determined using clone library sequencing of the 16S rRNA gene and phylogenetic inferences. Helicobacter spp. were detected by semi-nested PCR and FISH in freshwater enrichments from both sites. Coccoid viable but nonculturable (VBNC) cells were evidenced using 16S rRNA gene Helicobacter species and H. pylori-specific probes. Partial 16S rRNA gene sequences of two HP enrichments showed high similarity to H. pylori and Helicobacter nemestrinae (99-100 %). Other bacteria such as Serratia, Aquitalea, Chromobacterium, Mycobacterium, Acinetobacter, Curvibacter and Dysgonomonas were also detected using complete 16S rRNA gene sequences, with Serratia, Aquitalea and Chromobacterium the most common genera (40.9, 18.2 and 15.2 %, respectively). This is the first time that Helicobacter spp. have been reported in freshwaters of a tepui ecosystem. Our results contribute to the current knowledge of these bacteria in the aquatic environment and expand their known/potential sites outside the human host. PMID- 26825785 TI - A Biomechanical Analysis of an Artificial Disc With a Shock-absorbing Core Property by Using Whole-cervical Spine Finite Element Analysis. AB - STUDY DESIGN: A biomechanical comparison among the intact C2 to C7 segments, the C5 to C6 segments implanted with fusion cage, and three different artificial disc replacements (ADRs) by finite element (FE) model creation reflecting the entire cervical spine below C2. OBJECTIVE: The aim of this study was to analyze the biomechanical changes in subaxial cervical spine after ADR and to verify the efficacy of a new mobile core artificial disc Baguera C that is designed to absorb shock. SUMMARY OF BACKGROUND DATA: Scarce references could be found and compared regarding the cervical ADR devices' biomechanical differences that are consequently related to their different clinical results. METHODS: One fusion device (CJ cage system, WINNOVA) and three different cervical artificial discs (Prodisc-C Nova (DePuy Synthes), Discocerv (Scient'x/Alphatec), Baguera C (Spineart)) were inserted at C5-6 disc space inside the FE model and analyzed. Hybrid loading conditions, under bending moments of 1 Nm along flexion, extension, lateral bending, and axial rotation with a compressive force of 50 N along the follower loading direction, were used in this study. Biomechanical behaviors such as segmental mobility, facet joint forces, and possible wear debris phenomenon inside the core were investigated. RESULTS: The segmental motions as well as facet joint forces were exaggerated after ADR regardless of type of the devices. The Baguera C mimicked the intact cervical spine regarding the location of the center of rotation only during the flexion moment. It also showed a relatively wider distribution of the contact area and significantly lower contact pressure distribution on the core than the other two devices. A "lift off" phenomenon was noted for other two devices according to the specific loading condition. CONCLUSION: The mobile core artificial disc Baguera C can be considered biomechanically superior to other devices by demonstrating no "lift off" phenomenon, and significantly lower contact pressure distribution on core. LEVEL OF EVIDENCE: N/A. PMID- 26825786 TI - To the Editor. PMID- 26825787 TI - Efficacy of i-Factor Bone Graft versus Autograft in Anterior Cervical Discectomy and Fusion: Results of the Prospective, Randomized, Single-blinded Food and Drug Administration Investigational Device Exemption Study. AB - STUDY DESIGN: A prospective, randomized, controlled, parallel, single-blinded noninferiority multicenter pivotal FDA IDE trial. OBJECTIVE: The objective of this study was to investigate efficacy and safety of i-Factor Bone Graft (i Factor) compared with local autograft in single-level anterior cervical discectomy and fusion (ACDF) for cervical radiculopathy. SUMMARY OF BACKGROUND DATA: i-Factor is a composite bone substitute material consisting of the P-15 synthetic collagen fragment adsorbed onto anorganic bone mineral and suspended in an inert biocompatible hydrogel carrier. P-15 has demonstrated bone healing efficacy in dental, orthopedic, and nonhuman applications. METHODS: Patients randomly received either autograft (N = 154) or i-Factor (N = 165) in a cortical ring allograft. Study success was defined as noninferiority in fusion, Neck Disability Index (NDI), and Neurological Success endpoints, and similar adverse events profile at 12 months. RESULTS: At 12 months (follow-up rate 87%), both i Factor and autograft subjects demonstrated a high fusion rate (88.97% and 85.82%, respectively, noninferiority P = 0.0004), significant improvements in NDI (28.75 and 27.40, respectively, noninferiority P < 0.0001), and high Neurological Success rate (93.71% and 93.01%, respectively, noninferiority P < 0.0001). There was no difference in the rate of adverse events (83.64% and 82.47% in the i Factor and autograft groups, respectively, P = 0.8814). Overall success rate consisting of fusion, NDI, Neurological Success and Safety Success was higher in i-Factor subjects than in autograft subjects (68.75% and 56.94%, respectively, P = 0.0382). Improvements in VAS pain and SF-36v2 scores were clinically relevant and similar between the groups. A high proportion of patients reported good or excellent Odom outcomes (81.4% in both groups). CONCLUSION: i-Factor has met all four FDA mandated noninferiority success criteria and has demonstrated safety and efficacy in single-level ACDF for cervical radiculopathy. i-Factor and autograft groups demonstrated significant postsurgical improvement and high fusion rates. LEVEL OF EVIDENCE: 1. PMID- 26825788 TI - Two-year Comparative Outcomes of MIS Lateral and MIS Transforaminal Interbody Fusion in the Treatment of Degenerative Spondylolisthesis: Part I: Clinical Findings. AB - STUDY DESIGN: A prospective, multicenter, institutional review board (IRB) approved study with randomized and observational study arms. OBJECTIVE: The purpose of this study was to compare clinical outcomes between minimally invasive transforaminal (MIS TLIF) and MIS lateral interbody fusion (XLIF) in the treatment of patients with low-grade degenerative spondylolisthesis with stenosis through two years postoperative. SUMMARY OF BACKGROUND DATA: Few reports exist comparing different MIS approaches directly in the treatment of similar pathology, as most studies report differences between MIS and open procedures. METHODS: A total of 55 patients undergoing surgical treatment for degenerative spondylolisthesis with spinal stenosis at one or two contiguous levels between L1 and L5 were enrolled. Twenty-nine patients were treated with XLIF and 26 patients were treated with MIS TLIF. RESULTS: Operative time and length of stay were similar between the XLIF and MIS TLIF groups (171 vs 186 minutes; two days for each group). Blood loss was significantly lower in the XLIF group, with 79% of XLIF cases and 27% of MIS TLIF cases resulting in <100 mL of blood loss, P < 0.001. Hip flexion weakness was more common in the XLIF group (31%) than in the MIS TLIF group (0%). One patient in the XLIF group had a new distal motor weakness and three patients in the XLIF group and two patients in the MIS TLIF group had new sensory changes postoperatively, all of which resolved by 12 months postoperative. Back and leg pain for both XLIF and MIS TLIF groups improved significantly from baseline to 24 months postoperative, with 73% improvement in the XLIF and 64% in the MIS TLIF group. Worst leg pain showed similar improvements through two years postoperative, with a 79% decrease seen in the XLIF group and 74% in the MIS TLIF group. Disability (ODI) improved 53% in the XLIF group and 57% in the MIS TLIF group. CONCLUSION: Despite different mechanisms of action (indirect vs direct decompression), mid-term clinical outcomes between XLIF and MIS TLIF were similar. These two-year results suggest that both XLIF and MIS TLIF are reasonable MIS approaches for the treatment of lumbar degenerative pathology. LEVEL OF EVIDENCE: 2. PMID- 26825789 TI - Preservation or Restoration of Segmental and Regional Spinal Lordosis Using Minimally Invasive Interbody Fusion Techniques in Degenerative Lumbar Conditions: A Literature Review. AB - STUDY DESIGN: A literature review. OBJECTIVE: The purpose of this study was to review lumbar segmental and regional alignment changes following treatment with a variety of minimally invasive surgery (MIS) interbody fusion procedures for short segment, degenerative conditions. SUMMARY OF BACKGROUND DATA: An increasing number of lumbar fusions are being performed with minimally invasive exposures, despite a perception that minimally invasive lumbar interbody fusion procedures are unable to affect segmental and regional lordosis. METHODS: Through a MEDLINE and Google Scholar search, a total of 23 articles were identified that reported alignment following minimally invasive lumbar fusion for degenerative (nondeformity) lumbar spinal conditions to examine aggregate changes in postoperative alignment. RESULTS: Of the 23 studies identified, 28 study cohorts were included in the analysis. Procedural cohorts included MIS ALIF (two), extreme lateral interbody fusion (XLIF) (16), and MIS posterior/transforaminal lumbar interbody fusion (P/TLIF) (11). Across 19 study cohorts and 720 patients, weighted average of lumbar lordosis preoperatively for all procedures was 43.5 degrees (range 28.4 degrees -52.5 degrees ) and increased 3.4 degrees (9%) (range -2 degrees to 7.4 degrees ) postoperatively (P < 0.001). Segmental lordosis increased, on average, by 4 degrees from a weighted average of 8.3 degrees preoperatively (range -0.8 degrees to 15.8 degrees ) to 11.2 degrees at postoperative time points (range -0.2 degrees to 22.8 degrees ) (P < 0.001) in 1182 patient from 24 study cohorts. Simple linear regression revealed a significant relationship between preoperative lumbar lordosis and change in lumbar lordosis (r = 0.413; P = 0.003), wherein lower preoperative lumbar lordosis predicted a greater increase in postoperative lumbar lordosis. CONCLUSION: Significant gains in both weighted average lumbar lordosis and segmental lordosis were seen following MIS interbody fusion. None of the segmental lordosis cohorts and only two of the 19 lumbar lordosis cohorts showed decreases in lordosis postoperatively. These results suggest that MIS approaches are able to impact regional and local segmental alignment and that preoperative patient factors can impact the extent of correction gained (preserving vs. restoring alignment). LEVEL OF EVIDENCE: 4. PMID- 26825790 TI - Vertebral Hemangiomas and Their Correlation With Other Pathologies. AB - STUDY DESIGN: This cross-sectional study was carried out on 196 adults (98 men and 98 women), aged between 18 and 91 years. OBJECTIVE: To examine whether vertebral hemangiomas (VHs) are associated with other spinal pathologies, metabolic diseases, cardiovascular diseases, cancer and past trauma, to shed light on their possible pathophysiology. SUMMARY OF BACKGROUND DATA: VHs are the most common form of benign tumors in the spine. Their association with spinal and systemic pathologies has not yet been systematically studied. METHODS: Clinical data were gathered from full spine CT scans and medical records. RESULTS: VHs were significantly associated with disc lesions (P = 0.004), past trauma (P = 0.037), diabetes (chi = 5.179, P = 0.023), cardio-vascular diseases (chi = 8.625, P = 0.003), and cancer (chi = 5.820, P = 0.016), but not with obesity. Only medium-large size VHs were significantly associated with osteoporosis (chi = 6.695, P = 0.010). CONCLUSION: The pattern of diseases related to VHs suggests a common cause for VH, namely, a disruption of vascular flow in the microvessels (accompanied by endothelium damage) within the vertebral body, eventually resulting in hypervascularization. LEVEL OF EVIDENCE: 4. PMID- 26825791 TI - An Effective Treatment Option for Kummell Disease With Neurological Deficits: Modified Transpedicular Subtraction and Disc Osteotomy Combined With Long-Segment Fixation. AB - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To illustrate the technique of modified transpedicular subtraction and disc osteotomy combined with long segment fixation for the treatment of Kummell disease with neurologic deficits and to evaluate clinical and radiographic results of patients treated with the technique. SUMMARY OF BACKGROUND DATA: Kummell disease is a clinical condition in which patients develop a kyphosis in the lower thoracolumbar spinal region months to years after sustaining an otherwise asymptomatic minor spinal. Currently, for patients with neurological deficits, anterior decompression with bone grafting fusion, posterior decompression with pedicle subtraction osteotomy, or a combined anterior and posterior approach operation were used; however, there is no standard treatment and no single effective treatment for Kummell disease. METHODS: Between May 2009 and May 2012, we reviewed 12 patients experiencing Kummell disease with neurological deficits who underwent modified transpedicular subtraction and disc osteotomy combined with long-segment fixation. Preoperative and postoperative Cobb angle, visual analog scale, Asia Spinal Injury Association, and sagittal balance were documented. The patients were followed up for 33 months on average. RESULTS: The Cobb angles decreased from 43.33 +/- 7.44 degrees to 1.92 +/- 2.74 degrees (P < 0.01), the mean visual analog scale reduced from 7.17 +/- 1.27 degrees to 1.17 +/- 1.03 degrees (P < 0.01), and the sagittal vertical angle improved from 14.82 +/- 3.56 cm to 5.15 +/- 2.10 cm (P < 0.01). Kyphotic deformity was successfully corrected and solid fusion was achieved in all cases. Neurologic function of nine cases was improved to various degrees. CONCLUSION: Modified transpedicular subtraction and disc osteotomy combined with long-segment fixation is an effective treatment option for Kummell disease with neurological deficits. LEVEL OF EVIDENCE: 4. PMID- 26825792 TI - MIS Expandable Interbody Spacers: A Literature Review and Biomechanical Comparison of an Expandable MIS TLIF With Conventional TLIF and ALIF. AB - STUDY DESIGN: Biomechanical study and review of literature on expandable lumbar interbody fusion constructs. OBJECTIVE: To evaluate the biomechanical stability of expandable interbody devices. SUMMARY OF BACKGROUND DATA: Lumbar interbody implants placed from an anterior or lateral approach are desirable due to their large size, providing a stable fusion environment. Posterior implants are typically limited by their access corridor. Expandable footprint transforaminal lumbar interbody fusion (TLIF) interbodies may allow for a minimally invasive TLIF approach with the biomechanical benefits of an anterior lumbar interbody fusion (ALIF)-sized graft; however, this requires experimental investigation. METHODS: Six cadaveric L1-sacrum segments were tested intact with pure moments of +/- 7.5 N m in flexion-extension, lateral bending, and axial rotation. Specimens received at L4-5 either a medial-lateral expandable TLIF cage (MLX TLIF) or a conventional polyether ether ketone (PEEK) banana-shaped TLIF cage (Conv-TLIF) first. Both were tested with unilateral and bilateral pedicle screw (PS) fixation. Testing was repeated with the alternate cage and fixation. Motion marker arrays were fixed to L4 and L5 to assess range of motion. Results were compared with published data for a PEEK ALIF cage with anterior plate and a PEEK ALIF cage with bilateral PS fixation, tested under the same conditions. RESULTS: The most rigid construct was ALIF with bilateral PS fixation in flexion-extension and axial rotation, whereas MLX with bilateral PS was most rigid in lateral bending. Conv-TLIF with unilateral PS was the least rigid construct. MLX-TLIF with unilateral PS provided similar range of motion to Conv-TLIF with bilateral PS in flexion-extension and lateral bending, and ALIF with anterior plate in lateral bending. CONCLUSION: The MLX-TLIF cage with unilateral PS fixation provided comparable stability to conventional TLIF with bilateral PS fixation and ALIF with anterior plate treatments. The large footprint of the expandable cage may reduce the TLIF supplemental fixation demands and facilitate minimally invasive single-position surgery. If needed, additional stability may be achieved by using bilateral PS. LEVEL OF EVIDENCE: N/A. PMID- 26825793 TI - Comparative Effectiveness and Economic Evaluations of Open Versus Minimally Invasive Posterior or Transforaminal Lumbar Interbody Fusion: A Systematic Review. AB - STUDY DESIGN: Systematic review of randomized and nonrandomized comparative studies. OBJECTIVE: To summarize the literature examining comparative effectiveness and economic evaluation of minimally invasive versus open transforaminal/posterior lumbar interbody fusion (T/PLIF). SUMMARY OF BACKGROUND DATA: Minimally invasive approaches to lumbar fusion have been proposed as an alternative to open surgery to decrease patient morbidity and improve clinical and patient-reported outcomes, with the possibility of secondary cost-savings. The comparative clinical and economic effectiveness of minimally invasive versus open T/PLIF remains largely undetermined. METHODS: A systematic review of Medline, EMBASE, Web of Science, and Cochrane from database inception to September 2015 inclusive was performed. Reference lists were manually searched. Studies comparing MIS to open T/PLIF for degenerative lumbar conditions, including at least 10 patients in each arm and reporting at least one clinical, perioperative, radiographic, adverse event, or economic outcome, were included. RESULTS: Between database inception and October 2015, 45 studies meeting inclusion criteria were identified with 3472 subjects undergoing MIS fusion and 5925 having an open procedure. There were no significant differences in operative time between the two groups, whereas patients undergoing MIS fusion consistently demonstrated less blood loss (16.1-88.7%) and shorter hospital stays (15.0-64.0% shorter). There was no difference in variably reported VAS, ODI, SF-36, SF-12, or EQ-5D scores between the two techniques at intermediate to long-term follow-up (12-60 months). Complication rates and fusion rates were also equivalent between the two groups. Economic studies demonstrate cost-savings in favor of MIS fusion ranging from 2.5 to 49.3%. CONCLUSION: Limited quality comparative observational cohort and randomized controlled studies of MIS versus open T/PLIF consistently demonstrate improved perioperative outcomes including operative time, estimated blood loss, and length of stay with no significant difference in patient-reported outcomes or complication rates between the two groups at final follow-up. Increasing economic data suggest both direct and indirect cost-savings in favor of MIS fusion. LEVEL OF EVIDENCE: N/A. PMID- 26825795 TI - Validation of the Eating Pattern Inventory for Children in a General Population Sample of 11- to 12-Year-Old Children. AB - Previous research suggests that the Eating Pattern Inventory for Children (EPI-C) is best conceptualized as comprising four factors: dietary restraint, emotional, external eating and parental pressure to eat. This study aims to examine the psychometric properties of the EPI-C and to test gender and weight group differences. The population-based study sample comprised 1,939 children aged 11 to 12 years from the Copenhagen Child Cohort (CCC2000). Psychometric properties were evaluated using multigroup categorical data in confirmatory factor analysis (CFA) and differential item functioning (DIF) tests. CFA supported the four factor solution for the EPI-C. Reliability estimates were satisfactory for three of the four scales. DIF with regard to weight was found for an item on weight loss intention. Girls reported higher restrained and emotional eating; overweight children reported higher restrained, emotional and external eating, while underweight children reported higher parental pressure to eat. The results support the use of EPI-C for measuring eating behaviors in preadolescence. PMID- 26825796 TI - "Girl Power!": The Relationship between Women's Autonomy and Children's Immunization Coverage in Ethiopia. AB - BACKGROUND: Although immunizations are efficient and cost effective methods of reducing child mortality, worldwide, approximately 2 million children die yearly of vaccine-preventable diseases. Researchers and health organizations have detailed information on the positive relationship between women's autonomy and children's health outcomes in developing countries. METHODS: This study investigates the links between women's household autonomy and children's immunization status using data from a nationally representative sample of children aged 12-30 months (N = 2941) from the 2011 Ethiopia Demographic and Health Survey. RESULTS: The results showed that women's socioeconomic status and household autonomy were significantly associated with children's immunization status. CONCLUSION: Overall, the implications of this study align with those of the Millennium Development Goal #3: improvements in women's household autonomy are linked to more positive child health outcomes. PMID- 26825797 TI - Left heart bypass for thoracoabdominal aortic aneurysm repair: technical aspects. AB - There are different surgical techniques for providing circulatory support during the repair of thoracoabdominal aortic aneurysms. They all aim at reducing the afterload of the heart and the preservation of distal organ perfusion. Partial or total extracorporeal circulation with or without cooling and left heart bypass (LHB) are actually the most used surgical approaches. The objective of this study was to describe and comment on the technical aspects of the LHB. We briefly describe our results and put them into perspective based on the current literature. PMID- 26825798 TI - GP inspections are damaging patient care, shows practice survey. PMID- 26825799 TI - Plasma arachidonic and docosahexaenoic acids in Tunisian very low birth weight infants: status and association with selected neonatal morbidities. AB - To study plasma arachidonic acid (AA) and docosahexaenoic acid (DHA) status in Tunisian very low birth weight (VLBW) infants and their association with selected neonatal morbidities. A total of 709 VLBW infants and 339 term infants were included. Plasma fatty acids were analyzed using capillary gas chromatography. VLBW infants had significantly (p < 0.001) lower plasma AA (9.44 +/- 2.12 vs. 10.8 +/- 2.10) and DHA (2.56 +/- 0.89 vs. 3.46 +/- 1.09) levels, but higher n-6:n 3 ratio (5.58 +/- 1.22 vs. 5.17 +/- 1.46) than term infants. In VLBW infants, plasma AA and DHA were related to gestational age (r = 0.156; p = 0.001 and r = 0.134; p = 0.003, respectively), birthweight (r = 0.242; p < 0.001 and r = 0.181; p < 0.001, respectively) and head circumference (r = 0.138; p = 0.005 and r = 0.108; p = 0.027, respectively). Infants with respiratory distress syndrome have decreased plasma AA and DHA and those with intraventricular hemorrhage have decreased plasma AA and n-6:n-3 ratio. Sepsis was associated with decreased DHA levels. Plasma long chain polyunsaturated fatty acids status is low in VLBW infants. These deficits may enhance the risk of common neonatal morbidities, rendering their prevention and correction greatly warranted. PMID- 26825801 TI - The nasal vestibular body: anatomy, clinical features, and treatment considerations. AB - Nasal obstruction is a common presenting complaint, with many possible etiologies. Herein, we provide an introductory anatomic description, clinical relevance, and proposed nomenclature for an underappreciated soft tissue focus in the nasal vestibule-the nasal vestibular body (NVB)-that can contribute to nasal obstruction in a subset of patients. This is a small mound of dynamic soft tissue in the lateral aspect of the internal nasal valve, situated inferior and anterior to the head of the inferior turbinate that can be missed on routine examination for many salient reasons. In well-selected patients, whose symptoms of nasal obstruction may in part be secondary to the presence of this soft tissue focus, directed testing and tissue reduction can be performed. PMID- 26825800 TI - Cross-stress resistance in Saccharomyces cerevisiae yeast--new insight into an old phenomenon. AB - Acquired stress resistance is the result of mild stress causing the acquisition of resistance to severe stress of the same or a different type. The mechanism of "same-stress" resistance (resistance to a second, strong stress after mild primary stress of the same type) probably depends on the activation of defense and repair mechanisms specific for a particular type of stress, while cross stress resistance (i.e., resistance to a second, strong stress after a different type of mild primary stress) is the effect of activation of both a specific and general stress response program, which in Saccharomyces cerevisiae yeast is known as the environmental stress response (ESR). Advancements in research techniques have made it possible to study the mechanism of cross-stress resistance at various levels of cellular organization: stress signal transduction pathways, regulation of gene expression, and transcription or translation processes. As a result of this type of research, views on the cross-stress protection mechanism have been reconsidered. It was originally thought that cross-stress resistance, irrespective of the nature of the two stresses, was determined by universal mechanisms, i.e., the same mechanisms within the general stress response. They are now believed to be more specific and strictly dependent on the features of the first stress. PMID- 26825802 TI - Long-term results of one staged multilevel surgery with tongue suspension surgery or one level palatal surgery for treatment of moderate and severe obstructive sleep apnea. AB - The objective of this study is to evaluate and compare the long-term efficacy of the one staged multilevel surgery (MLS) with tongue suspension (TBS) surgery or one level palatal surgery for treatment of moderate and severe obstructive sleep apnea (OSA). This is a prospective cross-sectional study. SETTING: University hospital. Thirty-three patients diagnosed as moderate to severe OSA. Patients, with >= 50 % retropalopharyngeal obstruction on the Muller maneuver, were treated with palatal surgeries (PS) and patients, with >= 50 % retropalopharyngeal obstruction on the Muller maneuver with >= 50 % base of the tongue collapse, were treated with palatal surgeries and tongue suspension surgery (TBS). Patients were evaluated with one night polysomnography before the surgery and 24 months after the surgery. Patients completed Epworth sleepiness scale (ESS), snoring VAS (visual analog scale) before and 24 months after the surgery. Nine-teen patients with a mean age of 46.1 +/- 8.3 underwent palatal surgeries (PS) and 14 patients with a mean age of 41.4 +/- 8.9 underwent PS plus TBS. Success rate in TBS+PS group was 57.1 % and in PS group was 42.1 %. In both groups total apnea-hypopnea index (AHI) values significantly decreased after 2 years (p < 0.025) but there was no statistically significant difference between TBS+PS and PS groups. Supine AHI levels were reduced statistically significant in both groups postoperatively (p < 0.025). There was not any significant difference postoperatively in non supine AHI levels in both groups (p > 0.025). There were significant postoperative changes in ODI, AVO2, MOS, ESS, Snoring VAS values in PS group (p < 0.025). In TBS+PS group there was a significant difference postoperatively only in ODI values. Treatment of OSA patients with retropalatal or retropalatal and retroglossal obstruction, in a one staged surgery, is a safe and easy procedure. We have achieved favorable long-term outcomes in moderate-severe OSA patients undergoing both palatal surgery and tongue suspension surgery. PMID- 26825803 TI - WHO urges countries in dengue belt to look out for Zika. PMID- 26825804 TI - Copper diethyldithiocarbamate as an activator of Nrf2 in cultured vascular endothelial cells. AB - The interest in organic-inorganic hybrid molecules as molecular probes for biological systems has been growing rapidly. Such hybrid molecules exhibit unique biological activities. Herein, copper(II) bis(diethyldithiocarbamate) (Cu10) was found to activate the transcription factor NF-E2-related factor 2 (Nrf2), which is responsible for regulating antioxidant and phase II xenobiotic enzymes, in vascular endothelial cells. The copper complex rapidly accumulated within cells and induced nuclear translocation of Nrf2, leading to upregulation of the expression of downstream proteins without cytotoxic effects. However, while copper bis(2-hydroxyethyl)dithiocarbamate activated Nrf2, copper ion, diethyldithiocarbamate ligand with or without zinc or iron failed to exhibit this activity. Intracellular accumulation of Cu10 was higher than that of Cu(II) and Cu(I). While the accumulation of copper(II) bis(dimethyldithiocarbamate) was reduced by small interfering RNA (siRNA)-mediated knockdown of the copper transporter CTR1, the knockdown did not affect Cu10 accumulation, indicating that Cu10 rapidly enters vascular endothelial cells via CTR1-independent mechanisms. In addition, copper and iron complexes with other ligands tested could not activate Nrf2, suggesting that the intramolecular interaction between copper and dithiocarbamate ligand is important for the activation of the transcription factor. Cu10 induced the expression of heme oxygenase-1, NAD(P)H quinone oxidoreductase 1, and gamma-glutamylcysteine synthetase, downstream proteins of Nrf2. It was suggested that Cu10-induced activation of Nrf2 was due to proteasome inhibition as well as binding to Kelch-like ECH-associated protein 1. Since the effects of Cu10 on vascular endothelial cells are unique and diverse, the copper complex may be a good molecular probe to analyze the functions of the cells. PMID- 26825806 TI - Erratum to: Serum progesterone levels greater than 20 ng/ml on day of embryo transfer are associated with lower live birth and higher pregnancy loss rates. PMID- 26825805 TI - Ferritins: furnishing proteins with iron. AB - Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-alpha-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe(2+) oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores, consider how iron might be released from ferritins, and examine in detail how three selected ferritins oxidise Fe(2+) to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins. PMID- 26825808 TI - Dr. Wu Lien Teh, plague fighter and father of the Chinese public health system. PMID- 26825809 TI - Factors influencing uptake of voluntary counselling and testing services for HIV/AIDS in the Lower Manya Krobo Municipality (LMKM) in the Eastern Region of Ghana: a cross-sectional household survey. AB - BACKGROUND: Voluntary counselling and testing (VCT) is one of the nine strategies recommended for prevention and control of HIV globally. In this study, we assessed the awareness and utilisation of VCT services among residents of the Lower Manya Krobo Municipality (LMKM) in the Eastern Region of Ghana. METHODS: A population-based descriptive cross-sectional survey was conducted with 200 participants, aged between 18 and 55 years. Participants were recruited using cluster and simple random techniques to take part in the survey. Data was analysed descriptively, as well as using regression analysis approach. RESULTS: Ninety-one percent of the respondents surveyed were aware of VCT services for HIV/AIDS. Seventy percent (70 %) have used VCT service in the last 12 months prior to the survey. Of this proportion, 97% were satisfied with the quality of VCT services offered and indicated their willingness to recommend the service to others. Participants desire to know their HIV status (40%), referral by health workers (25%), and participants who wanted to get married (11%) were the main reasons for increased uptake. Participants who had formal education, primary (OR = 1.8 (95% CI 1.25-2.84)), junior high school (OR = 2.3 (95% CI 1.54-3.37)), senior high school (OR = 2.8 (95% CI 1.73-4.78)), and tertiary (OR = 3.4 (95% CI 1.98-8.42)), had increased chance of using VCT service compared with participants who had no education (p < 0.001). Reasons for non-utilisation of VCT service were lack of awareness of the VCT service in the area (32%), fear of being stigmatised (53 %), and the belief that HIV/AIDS cannot be cured and therefore the lack of need (5%). CONCLUSIONS: Although awareness and utilisation of VCT service rates were reportedly high, more efforts need to be done in order to increase awareness and promote utilisation. HIV/AIDS educational campaign programmes need to be strongly pursued, with emphasis on the benefits of VCT services. This has the potential of reducing stigma and increase utilisation. PMID- 26825807 TI - The axoneme: the propulsive engine of spermatozoa and cilia and associated ciliopathies leading to infertility. AB - This review article provides a critical analysis of the structure and molecular mechanisms of the microtubule axoneme of cilia and sperm flagella and their associated elements required for male fertility.A broad range of genetic and molecular defects (ciliopathies) are considered in the context of human diseases involving impaired motility in cilia and sperm flagella, providing provocative thought for future research in the area of male infertility. PMID- 26825810 TI - Characterization of a novel bioreactor system for 3D cellular mechanobiology studies. AB - In vitro engineering systems can be powerful tools for studying tissue development in response to biophysical stimuli as well as for evaluating the functionality of engineered tissue grafts. It has been challenging, however, to develop systems that adequately integrate the application of biomimetic mechanical strain to engineered tissue with the ability to assess functional outcomes in real time. The aim of this study was to design a bioreactor system capable of real-time conditioning (dynamic, uniaxial strain, and electrical stimulation) of centimeter-long 3D tissue engineered constructs simultaneously with the capacity to monitor local strains. The system addresses key limitations of uniform sample loading and real-time imaging capabilities. Our system features an electrospun fibrin scaffold, which exhibits physiologically relevant stiffness and uniaxial alignment that facilitates cell adhesion, alignment, and proliferation. We have demonstrated the capacity for directly incorporating human adipose-derived stromal/stem cells into the fibers during the electrospinning process and subsequent culture of the cell-seeded constructs in the bioreactor. The bioreactor facilitates accurate pre-straining of the 3D constructs as well as the application of dynamic and static uniaxial strains while monitoring bulk construct tensions. The incorporation of fluorescent nanoparticles throughout the scaffolds enables in situ monitoring of local strain fields using fluorescent digital image correlation techniques, since the bioreactor is imaging compatible, and allows the assessment of local sample stiffness and stresses when coupled with force sensor measurements. In addition, the system is capable of measuring the electromechanical coupling of skeletal muscle explants by applying an electrical stimulus and simultaneously measuring the force of contraction. The packaging of these technologies, biomaterials, and analytical methods into a single bioreactor system has produced a powerful tool that will enable improved engineering of functional 3D ligaments, tendons, and skeletal muscles. Biotechnol. Bioeng. 2016;113: 1825-1837. (c) 2016 Wiley Periodicals, Inc. PMID- 26825811 TI - Prenatal unilateral cerebellar hypoplasia diagnosed as PHACE syndrome. PMID- 26825812 TI - Traumatic atlantoaxial rotatory dislocation and displaced ossiculum terminale epiphysiolysis treated with a halo device: a case report. AB - INTRODUCTION: The horizontal synchondroses of the infant axis are biomechanical weak regions in trauma. CASE: We report the case of a 6-year-old girl who presented with delayed atlantoaxial dislocation and displaced ossiculum terminale epiphysiolysis after a fall from a tree. TREATMENT: The patient was treated with halo traction for 3 days after which a CT scan showed normal position of the C1/C2 joint, and an acceptable position of the ossiculum terminale whereafter a halo brace was applied. Because of delayed union on CT scans, the treatment was prolonged to a total of 21 weeks. RESULT: At final follow-up 26 months after halo brace removal, the patient demonstrated normal range of movement of the neck on clinical examination and radiographs of the cervical spine including lateral flexion/extension radiographs showed no sign of instability of the atlantoaxial joint. DISCUSSION: Conservative treatment with a halo device versus surgical treatment is discussed. PMID- 26825813 TI - Novel anatomic adaptation of cortical bone to meet increased mineral demands of reproduction. AB - The goal of this study was to investigate the effects of reproductive adaptations to mineral homeostasis on the skeleton in a mouse model of compromised mineral homeostasis compared to adaptations in control, unaffected mice. During pregnancy, maternal adaptations to high mineral demand include more than doubling intestinal calcium absorption by increasing calcitriol production. However, calcitriol biosynthesis is impaired in HYP mice, a murine model of X-linked hypophosphatemia (XLH). In addition, there is a paucity of mineralized trabecular bone, a primary target of bone resorption during pregnancy and lactation. Because the highest density of mineral is in mature cortical bone, we hypothesized that mineral demand is met by utilizing intracortical mineral reserves. Indeed, analysis of HYP mice revealed dramatic increases in intracortical porosity characterized by elevated serum PTH and type-I collagen matrix-degrading enzyme MMP-13. We discovered an increase in carbonate ion substitution in the bone mineral matrix during pregnancy and lactation of HYP mice, suggesting an alternative mechanism of bone remodeling that maintains maternal bone mass during periods of high mineral demand. This phenomenon is not restricted to XLH, as increased carbonate in the mineral matrix also occurred in wild-type mice during lactation. Taken together, these data suggest that increased intracortical perilacunar mineral turnover also contributes to maintaining phosphate levels during periods of high mineral demand. Understanding the mechanisms of skeletal contribution to mineral homeostasis is important to improving the treatment and prevention of fracture risk and bone fragility for female patients with XLH, but also provides important insight into the role and unique adaptations of the maternal skeleton to the demands of fetal development and the needs of postnatal nutrition. PMID- 26825814 TI - Emerging regulators of BMP bioavailability. PMID- 26825815 TI - A crucial role for upstream regulators of the bone morphogenetic protein (BMP) signaling in osteoblast differentiation. PMID- 26825816 TI - Is there an Increase in Valgus Deviation in Tibial Distraction Using the Lengthening Over Nail Technique? AB - BACKGROUND: During tibial lengthening, the soft tissues of the posterolateral compartment produce distraction-resisting forces causing valgus angulation. Although this occurs with the classic Ilizarov method, whether a valgus deformity develops with the lengthening over nail (LON) technique is questioned, because the intramedullary nail is thought to resist deforming forces and adequately maintain alignment of the distracted bone. QUESTIONS/PURPOSES: The purposes of this study were to (1) determine the amount of valgus deviation during tibial lengthening with the LON technique; and (2) analyze the factors that may be associated with valgus deviation with the LON technique. METHODS: Between June 2009 and September 2013, we performed 346 tibial lengthenings using the LON technique, lengthening and then nail technique, or lengthening with an intramedullary lengthening device. Sixty patients (120 tibias) who underwent bilateral lower leg lengthening with the LON technique were enrolled in this retrospective study. To limit the number of variables, we analyzed only the right tibia in all patients (60 tibias). The mean followup was 42 months (range, 26-71 months). The mean age of the patients was 25 years (range, 18-40 years). There were 36 male and 24 female patients. The mean final length gain was 67 +/- 9 mm. The mean time for distraction was 100 +/- 25 days. The overall valgus deviation was assessed by measuring the change in the medial proximal tibial angle and mechanical femorotibial angle on radiographs obtained before and after surgery and after completion of lengthening. Several demographic, surgical, and distraction-related variables were considered possible factors to prevent valgus deviation: proximal fixation method; presence of a blocking screw; diameter and length of the intramedullary nail; degree of nail insertion; length of the nail in the distal segment after completion of distraction; final length gain; and patient's BMI. During the period studied, the blocking screw was to maintain the mechanical axis in patients who had neutral or valgus alignment preoperatively, or to prevent more valgus change in patients who underwent acute correction of varus deformity intraoperatively. Uni- and multivariate analyses were conducted. RESULTS: Valgus deviation occurred during the tibial LON. The medial proximal tibial angle increased from 86 degrees (95% CI, 85 degrees -86 degrees ) to 90 degrees (95% CI, 89 degrees -91 degrees ) (p < 0.001). The mechanical femorotibial angle changed from 2.2 degrees varus (95% CI, 3 degrees -1.4 degrees varus) to 2.6 degrees valgus (95% CI, 1.8 degrees -3.4 degrees valgus) (p < 0.001). Valgus deviation was evident in proximal and distal segments. In the multivariate regression model, use of a blocking screw was the only factor that was associated with decreased valgus deviation, and its effect size, although detectable, was small (-2.62; 95% CI, -4.65 to -0.59; p = 0.013). CONCLUSIONS: We found that valgus deviation does occur during tibial lengthening using the LON technique, but that blocking screw placement may help to minimize the likelihood that severe valgus deviation will occur. Future prospective studies should be conducted to confirm this preliminary finding. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 26825817 TI - Intravenous fluids for migraine: a post hoc analysis of clinical trial data. AB - BACKGROUND: A total of 1.2 million patients present to US emergency departments (EDs) annually with migraine headache. Intravenous fluid (IVF) hydration is used to treat acute migraine commonly. We were unable to identify published data to support or refute this practice. The goal of this analysis was to determine if administration of IVF is associated with improved short-term (1 hour) or sustained (24 hours) migraine outcomes. METHODS: This was a post hoc analysis of data collected from 4 ED-based migraine clinical trials in which patients were randomized to treatment with intravenous metoclopramide. In each of these studies, patients were administered IVF at the discretion of the treating physician. Our primary short-term outcome was improvement in 0 to 10 pain scale between baseline and 1 hour later. Our primary sustained outcome was the attainment of sustained headache freedom, defined as achieving a headache level of "none" in the ED and maintaining a level of "none" without headache recurrence throughout the 24- to 48-hour follow-up period. We compared mean improvement in pain scores between baseline and 1 hour later between those patients who received IVF and those who did not. We also compared the frequency of sustained headache freedom between both groups. We then used regression models to elucidate how nausea at baseline and the baseline pain score modified the relationship between IVF and the 2 outcomes. RESULTS: A total of 570 patients were included in the analysis. Of these, 112 (20%) were treated with IVF. Patients who received IVF improved by 4.5 (95% confidence interval [CI], 4.0-5.0) on the 0 to 10 scale, whereas patients who did not receive IVF improved by 5.1 (95% CI, 4.8-5.3) (95% CI for difference of 0.6, 0-1.1). Of patients who received IVF, 14% (95% CI, 9 22%) enjoyed sustained headache freedom vs 18% (95% CI, 15%-22%) of patients who did not (95% CI for difference of 4%, -4% to 11%). In the linear regression model, IVF was associated with less improvement in 0 to 10 pain score between baseline and 1 hour (B coefficient, -0.6; 95% CI, -1.1 to 0; P=.05). In the logistic regression model, IVF administration was not associated with sustained headache freedom (odds ratio, 0.8; 95% CI, 0.4-1.5; P=.52). CONCLUSION: Intravenous fluid did not improve pain outcomes among patients with acute migraine who were treated with intravenous metoclopramide. PMID- 26825818 TI - White rice consumption and risk of esophageal cancer in Xinjiang Uyghur Autonomous Region, northwest China: a case-control study. AB - This study investigated the association between white rice consumption and the risk of esophageal cancer in remote northwest China, where the cancer incidence is known to be high. A case-control study was conducted during 2008-2009 in Urumqi and Shihezi, Xinjiang Uyghur Autonomous Region of China. Participants were 359 incident esophageal cancer patients and 380 hospital-based controls. Information on habitual white rice consumption was obtained by personal interview using a validated semi-quantitative food frequency questionnaire. Logistic regression analyses were performed to assess the association between white rice consumption and the esophageal cancer risk. Confounding variables including socio demographics, family history, dietary and lifestyle factors were adjusted in the multivariate model. The esophageal cancer patients reported lower consumption levels of white rice-based products, including cooked white rice and porridge, when compared to the control group. Overall, regular consumption of white rice foods was inversely associated with the esophageal cancer risk, the adjusted OR being 0.34 (95% CI 0.23 to 0.52) for the highest (>250 g) versus the lowest (<92 g) tertile of daily intake. Similar reductions in risk were also apparent for high consumption levels of cooked white rice and porridge. In conclusion, habitual white rice consumption was associated with a reduced risk of esophageal cancer for adults residing in northwest China. Our findings provide evidence to support the continued consumption of white rice. PMID- 26825819 TI - Effect of biosurfactants on Pseudomonas aeruginosa and Staphylococcus aureus biofilms in a BioFlux channel. AB - Recent studies have indicated that biosurfactants play a role both in maintaining channels between multicellular structures in biofilms and in dispersal of cells from biofilms. A combination of caprylic acid (0.01 % v/v) together with rhamnolipids (0.04 % v/v) was applied to biofilms of Pseudomonas aeruginosa ATCC 15442, Staphylococcus aureus ATCC 9144 and a mixed culture under BioFlux flowthrough conditions and caused disruption of the biofilms. The biofilms were also treated with a combination of rhamnolipids (0.04 % v/v) and sophorolipids (0.01 %). Control treatments with PBS 1* had no apparent effect on biofilm disruption. The Gram-positive bacterium (S. aureus ATCC 9144) was more sensitive than P. aeruginosa ATCC 15442 in terms of disruption and viability as shown by Live/Dead staining. Disruption of biofilms of P. aeruginosa ATCC 15442 was minimal. Oxygen consumption by biofilms, after different treatments with biosurfactants, confirms that sophorolipid on its own is unable to kill/inhibit cells of P. aeruginosa ATCC 15442, and even when used in combination with rhamnolipids, under static conditions, no decrease in the cell viability was observed. Cells in biofilms exposed to mono-rhamnolipids (0.04 % v/v) showed behaviour typical of exposure to bacteriostatic compounds, but when exposed to di rhamnolipids (0.04 % v/v), they displayed a pattern characteristic of bactericidal compounds. PMID- 26825821 TI - Bioconcrete: next generation of self-healing concrete. AB - Concrete is one of the most widely used construction materials and has a high tendency to form cracks. These cracks lead to significant reduction in concrete service life and high replacement costs. Although it is not possible to prevent crack formation, various types of techniques are in place to heal the cracks. It has been shown that some of the current concrete treatment methods such as the application of chemicals and polymers are a source of health and environmental risks, and more importantly, they are effective only in the short term. Thus, treatment methods that are environmentally friendly and long-lasting are in high demand. A microbial self-healing approach is distinguished by its potential for long-lasting, rapid and active crack repair, while also being environmentally friendly. Furthermore, the microbial self-healing approach prevails the other treatment techniques due to the efficient bonding capacity and compatibility with concrete compositions. This study provides an overview of the microbial approaches to produce calcium carbonate (CaCO3). Prospective challenges in microbial crack treatment are discussed, and recommendations are also given for areas of future research. PMID- 26825820 TI - Microbial communities from 20 different hydrogen-producing reactors studied by 454 pyrosequencing. AB - To provide new insight into the dark fermentation process, a multi-lateral study was performed to study the microbiology of 20 different lab-scale bioreactors operated in four different countries (Brazil, Chile, Mexico, and Uruguay). Samples (29) were collected from bioreactors with different configurations, operation conditions, and performances. The microbial communities were analyzed using 16S rRNA genes 454 pyrosequencing. The results showed notably uneven communities with a high predominance of a particular genus. The phylum Firmicutes predominated in most of the samples, but the phyla Thermotogae or Proteobacteria dominated in a few samples. Genera from three physiological groups were detected: high-yield hydrogen producers (Clostridium, Kosmotoga, Enterobacter), fermenters with low-hydrogen yield (mostly from Veillonelaceae), and competitors (Lactobacillus). Inocula, reactor configurations, and substrates influence the microbial communities. This is the first joint effort that evaluates hydrogen producing reactors and operational conditions from different countries and contributes to understand the dark fermentation process. PMID- 26825822 TI - Exploring Morphologic and Molecular Aspects of Endometrial Cancer Under Progesterone Treatment in the Context of Fertility Preservation. AB - OBJECTIVE: The standard treatment of early-stage (FIGO [International Federation of Gynecology and Obstetrics] I) endometrioid endometrial cancer (EEC) is hysterectomy with bilateral salpingo-oophorectomy. An alternative approach for younger women with low-grade EEC who wish to preserve fertility may be hormonal treatment. Previous studies have suggested that progesterone may elicit its antitumor effect in EEC by interacting with the Wingless (Wnt) and/or phosphatidylinositol 3-kinase (PI3K)/Akt pathways. Therefore, we explored whether common activating genetic alterations in Wnt and PI3K/Akt signaling correlated with nonresponsiveness to progesterone therapy for low-grade EEC. In addition, we investigated whether benign morphology under progesterone treatment is accompanied by the absence of genetic changes. METHODS: We analyzed molecular alterations in the Wnt and PI3K/Akt signaling in 84 serial endometrial samples from 11 premenopausal patients with progesterone receptor-positive low-grade EEC conservatively treated with progesterone and correlated these with histological and clinical follow-up. RESULTS: There were 6 responders and 5 nonresponders to progesterone treatment. The response rate to progesterone treatment was 55%, and the relapse rate was 83%. All responders had alterations in both the Wnt and PI3K/Akt pathway before treatment. In the nonresponder group, tumors inconsistently showed alterations in none, 1, or both pathways. Normalization of the endometrium morphology under progesterone treatment is accompanied by the absence of the genetic changes found in the specimen before treatment. CONCLUSIONS: We found that activating molecular alterations in either Wnt or PI3K/Akt signaling pathways did not predict resistance to progesterone treatment. It seems that morphological response goes along with disappearance of the established mutations. This exploratory study suggests that Wnt or PI3K/Akt status is unable to predict response to progesterone treatment in patients with EEC. PMID- 26825823 TI - Role of Adjuvant Therapy for Stage IA Serous and Clear Cell Uterine Cancer: Is Observation a Valid Strategy? AB - OBJECTIVES: The adjuvant treatment of early stage IA serous and clear cell carcinomas of the uterus is controversial. The aims of the study were to report on a single institution experience treating these high-risk early uterine cancers and to identify women who may be suitable for observation alone. METHODS AND MATERIALS: A retrospective review of patients presenting from 2003 to 2013 with pathologic stage IA (International Federation of Gynecology and Obstetrics 2009) serous or clear cell uterine carcinoma was performed. Patient and disease characteristics, surgical staging, treatment details, and recurrence data were collected. Recurrence rates and 5-year actuarial estimates of recurrence free survival (RFS) were the primary outcomes of interest. RESULTS: A total of 77 patients with stage IA were identified. Median (range) follow-up was 34 (1-108) months. Staging lymphadenectomy was performed in 83%. Adjuvant treatment was given to 27 patients, whereas 50 underwent observation. There were 12 recurrences total, with the 5-year RFS 79% for the cohort, with no statistically significant difference between observation and adjuvant treatment. Only 4 patients received adjuvant chemotherapy and none recurred. In the observation cohort, the presence versus absence of myometrial invasion showed a trend to poorer 5-year RFS (75% vs 93%, P = 0.06). CONCLUSIONS: Observation seems to be a valid strategy in those patients with stage IA serous and clear cell carcinoma without myometrial invasion. The presence of any myometrial invasion may confer a higher risk of recurrence, although further studies are needed to determine the optimal adjuvant treatment regimen. PMID- 26825824 TI - Continuous Low-Dose Oral Cyclophosphamide and Methotrexate as Maintenance Therapy in Patients With Advanced Ovarian Carcinoma After Complete Clinical Response to Platinum and Paclitaxel Chemotherapy. AB - PURPOSE: The aim of this study was to evaluate efficacy and safety of continuous, low dose of oral, metronomic chemotherapy as maintenance therapy in patients with advanced ovarian carcinoma after complete clinical response to platinum and paclitaxel chemotherapy. PATIENTS AND METHODS: In this nonrandomized study, patients older than 18 years, with Eastern Cooperative Oncology Group performance status less than 2, with advanced ovarian carcinoma after complete clinical response to platinum and paclitaxel chemotherapy were enrolled in 2 arms--arm A (maintenance arm), treated with continuous low-dose oral cyclophosphamide 50 mg and methotrexate 2.5 mg, and arm B (observation arm). Both arms were followed up for progression-free survival and toxicity. RESULTS: Thirty patients were accrued in each arm from January 2009 to December 2010 in Ain Shams University Hospitals, where they received the treatment and followed up for disease progression and toxicity. Patients had a median age of 53 years in maintenance arm and 52.5 years in the observational arm, respectively. Over 80% had papillary serous adenocarcinoma, and over 40% of them had a stage IV disease in both arms. After median follow-up of 27 months, patients achieved median progression-free survival of 18 months in maintenance arm (A) and 15.5 months in observational arm (B), respectively. Toxicity profile was excellent with no grade 3 or 4 toxicity reported. CONCLUSIONS: Current study may provide an evidence of efficacy and tolerability of continuous low-dose oral cyclophosphamide and methotrexate as a maintenance therapy in patients with advanced ovarian carcinoma after complete clinical response to platinum and paclitaxel chemotherapy. PMID- 26825825 TI - Primary Fallopian Tube Carcinoma: A Single-Institution Experience of 101 Cases: A Retrospective Study. AB - OBJECTIVE: This study aimed to identify the prognostic factors for primary fallopian tube carcinoma. METHODS: A retrospective analysis was conducted of the patients treated with primary surgery and adjuvant chemotherapy at the Obstetrics and Gynecology Hospital of Fudan University from February 2003 to December 2010. Cox proportional hazards model was used for univariate and multivariate survival analysis. RESULTS: Included in this study were 101 patients with a median follow up of 64 months and a mean age of 57 years. Latzko triad symptom of abdominal pain, vaginal bleeding or discharge, and palpable pelvic mass was reported in 14 patients, and elevated CA 125 (>= 35 U/mL) was found in 63. Four patients were classified as grade 1, 31 were grade 2, and 66 were grade 3. The distribution of International Federation of Gynecology and Obstetrics stage was 33 at stage I, 28 at stage II, 39 at stage III, and 1 at stage IV. Ninety patients underwent optimal tumor debulking in which residual tumor was no larger than 1 cm, and 67 patients received no fewer than 6 cycles of postoperative chemotherapy with paclitaxel and carboplatin (TP)-based regimen. Recurrence occurred in 44 patients after a median of 20 months (range, 1-72 months). The 5-year overall survival rate was 67.7%, and the 5-year disease-free survival was 57.4%. Multivariate analysis revealed that International Federation of Gynecology and Obstetrics stage (I-II) [hazard ratio (HR), 2.670; 95% confidence interval (CI), 1.316 5.418; P = 0.007 vs HR, 2.716; 95% CI, 1.416-5.211; P = 0.003], pelvic lymphadenectomy (HR, 0.274; 95% CI, 0.136-0.555; P < 0.001 vs HR, 0.449; 95% CI, 0.227-0.888; P = 0.021), and cycles (>= 6) of chemotherapy (HR, 0.480; 95% CI, 0.246-0.937; P = 0.031 vs HR, 0.521; 95% CI, 0.276-0.985; P = 0.045) might serve as independent predictors of both overall survival and disease-free survival. CONCLUSIONS: Preoperative diagnosis of fallopian tube carcinoma is difficult due to the silent course of this neoplasm. Comprehensive surgical staging including pelvic lymphadenectomy followed by adequate cycles of chemotherapy is an important strategy to improve patients' prognosis. PMID- 26825826 TI - Surgical and Oncological Outcome of Robotic Surgery Compared With Laparoscopic and Abdominal Surgery in the Management of Locally Advanced Cervical Cancer After Neoadjuvant Chemotherapy. AB - OBJECTIVE: The primary aim is to evaluate the surgical and oncological outcome of robotic radical hysterectomy (RRH) plus pelvic lymphadenectomy in locally advanced cervical cancer (LACC) after neoadjuvant chemotherapy (NACT). The secondary aim is to compare the surgical and oncological results of RRH after NACT with a historical cohort of patients undergoing laparoscopic radical hysterectomy or abdominal radical hysterectomy plus pelvic lymphadenectomy for LACC after NACT. METHODS: We enrolled a total of 41 patients in this study with LACC undergoing RRH, who achieved a clinical partial or complete response to NACT. The surgical and oncological outcomes of 2 historical groups were compared: the laparoscopic group (41 patients) with the laparotomic group (43 patients). RESULTS: The median estimated blood loss, operative time, and length of hospital stay were statistically significant and in favor of the robotic group. No conversion to laparotomy in the robotic group was necessary. There were no significant differences between the 3-year overall survival and disease-free survival rates in the minimally invasive groups; nevertheless, the robotic group showed the same recurrence rate of laparoscopic in a short-interval follow-up. CONCLUSIONS: The robotic approach could be considered a feasible and safe alternative to other surgical options. Multicenter randomized clinical trials with longer follow-ups are necessary to evaluate the overall oncologic outcomes of this procedure. PMID- 26825827 TI - Clinical and Oncologic Outcomes of Robotic Versus Abdominal Radical Hysterectomy for Women With Cervical Cancer: Experience at a Referral Cancer Center. AB - OBJECTIVES: To compare the clinical and oncologic outcomes of robotic radical hysterectomy (RRH) vs abdominal radical hysterectomy (ARH) in patients with cervical carcinoma. METHODS: A retrospective analysis of women who underwent radical hysterectomy for cervical cancer from December 2006 to December 2014 at European Institute of Oncology was performed. Patients who underwent RRH were compared with women operated on by ARH. The groups were matched by age, body mass index, tumor size, International Federation of Gynecology and Obstetrics stage, comorbidity, previous neoadjuvant chemotherapy, histology type, and tumor grade. RESULTS: A total of 203 and 104 women who underwent RRH and ARH, respectively, were analyzed. Baseline characteristics, stage of disease, histology type, and grade of differentiation were similar between groups. Surgical time was significantly shorter in the ARH group (208 vs 282 minutes, P <= 0.001). Robotic radical hysterectomy was associated with significantly less estimated blood loss (219 vs 104 mL, P = 0.001) and with significantly shorter hospital stay (5.2 vs 3.9 days, P <= 0.001). Abdominal radical hysterectomy was correlated with a significantly higher number of lymph nodes removed (25.8 vs 22, P = 0.003). None of the robotic procedures required conversion to laparotomy. A significantly higher number of patients in ARH required postoperative transfusion (11 [10.5%] vs 6 [2.9%], P = 0.006). Lower extremity lymphedema was significantly higher in ARH (28 [27.5%] vs 17 [8.3%], P = 0.001). Recurrence rates as well as progression free survival and overall survival were similar between groups at a median follow up of 41.64 months. CONCLUSIONS: Robotic radical hysterectomy is safe and feasible and is associated with improved clinical outcomes. Although longer follow-up is needed, early data show equivalent oncologic outcomes compared with other surgical modalities. PMID- 26825828 TI - Radical Hysterectomy and Total Abdominal Vaginectomy for Primary Vaginal Cancer. AB - The aim of this surgical video is to demonstrate en bloc radical removal of uterus and vagina in a patient with clinical early-stage vaginal cancer. Surgical treatment was offered to our patient for clinical early-stage primary vaginal cancer. An en bloc radical hysterectomy, systematic pelvic lymphadenectomy, and total abdominal vaginectomy were performed. Postoperative adjuvant radiation or chemotherapy was not recommended for completely resected pathologic stage I disease with no lymph node involvement and negative surgical margins. Radical surgery can be a treatment option for selected patients with primary vaginal cancer. PMID- 26825829 TI - Feasibility Study of Adjuvant Chemotherapy Using Taxane Plus Carboplatin for High Risk Patients With Uterine Cervical Non-Squamous Cell Carcinoma After Radical Hysterectomy. AB - OBJECTIVE: We conducted this study to evaluate the efficacy and safety of adjuvant chemotherapy using taxane plus carboplatin (CBDCA) for high-risk stage IB-IIB patients with uterine cervical non-squamous cell carcinoma after radical hysterectomy. METHODS: Thirty-seven patients were eligible. Pelvic lymph node involvement and/or parametrial invasion were defined as high-risk factors. The patients were treated with 6 cycles of paclitaxel (PTX, 175 mg/m(2)) or docetaxel (DTX, 60 mg/m(2)) followed by CBDCA (area under the curve, 6) every 3 weeks. The primary end point was 2-year progression-free survival (PFS) rate, and the secondary end point was the assessment of adverse events. RESULTS: Twenty-two patients received PTX/CBDCA (TC) chemotherapy, and the remaining 15 patients underwent DTX/CBDCA (DC) chemotherapy. The 2-year PFS rate was 62.1% (95% confidence interval, 44.6%-75.5%). Patients receiving DC chemotherapy showed a better 2-year PFS rate compared to those with TC chemotherapy, but the difference was not statistically significant (80.0% vs 50.0%, P = 0.1400). The most common grade 3/4 adverse events were hematologic toxicities, which were generally well tolerable. Nonhematologic toxicity was generally mild. CONCLUSIONS: Taxane and CBDCA combination chemotherapy, especially DC chemotherapy, may be one of the useful adjuvant treatments for high-risk stage IB-IIB patients with uterine cervical non-squamous cell carcinoma after radical hysterectomy. PMID- 26825830 TI - The Value of Secondary Cytoreductive Surgery in Recurrent Ovarian Cancer and Application of a Prognostic Score. AB - OBJECTIVES: Secondary cytoreductive surgery (SCS) is an option for treating patients with recurrent ovarian cancer. Three ongoing randomized trials are comparing SCS plus chemotherapy with chemotherapy alone, and few comparative studies have been published. MATERIALS AND METHODS: We performed a retrospective review of data on 209 patients with recurrent ovarian carcinoma who were treated at a single institution from 2000 to 2013. We analyzed prognostic factors in the recurrence setting to determine the value of SCS in a multivariate model, including propensity score, by prognostic group. RESULTS: In the univariate analysis, younger than 65 years, personal or family history of breast or ovarian cancer, stage I-II at diagnosis, residual disease 10 mm or less after primary debulking surgery, performance status 1 or less, CA125 less than 100, only 1 metastatic site of recurrence, platinum-free interval of more than 12 months, and SCS correlated with better overall survival. In the multivariate model, including propensity score, SCS remained associated with a 66% decrease in the risk of death (hazard ratio, 0.34; 95% CI, 0.15-0.76, P = 0.008). Secondary cytoreductive surgery was also linked to longer progression-free survival (hazard ratio, 0.50; 95% CI, 0.30-0.84, P = 0.008). There was no evidence of a benefit of SCS in patients with unfavorable prognosis (P for interaction = 0.654). CONCLUSIONS: Our results confirm the benefit of SCS in progression-free survival and overall survival in the recurrent setting and suggest that it exists not only for patients with a good prognosis. PMID- 26825832 TI - Long-term Benefit of Tumor Volume-Directed Involved Field Radiation Therapy in the Management of Recurrent Ovarian Cancer. AB - OBJECTIVES: This study aimed to report on long-term effectiveness of involved field radiation therapy (IFRT) in the salvage of localized recurrent ovarian cancer (ROC). METHODS: A retrospective analysis of 27 patients with a diagnosis of epithelial ovarian cancer who received tumor volume-directed IFRT for localized extraperitoneal recurrences (either as consolidation after cytoreductive surgery (CRS) or as attempted salvage if unresectable) forms the basis of this report. All patients were heavily pretreated with multiple chemotherapy regimens. Involved field radiation therapy was primarily with external beam (median dose, 50.4 Gy). Local recurrence-free survival (LRFS) was defined as freedom from in-field recurrences and was considered as a measure of effectiveness of radiotherapy. Statistical analyses evaluated association between disease-free survival, overall survival, LRFS, and various prognostic factors. Comparison was also made with a similar but unmatched cohort with localized recurrences salvaged by additional chemotherapy instead of local therapies (NIFRT group). RESULTS: Of 27 patients, 17 had optimal CRS before RT. The actuarial survival at 5 and 10 years (in parenthesis) from date of radiation were LRFS (70% and 60%), overall survival (30% and 19%), and disease-free survival (33% and 20%). None of the NIFRT patients survived beyond 5 years from initiation of salvage chemotherapy. CONCLUSIONS: Long-term follow-up in this selected series confirmed the benefit of IFRT (+/-CRS) in localized ROC. Chemotherapy salvage in a similar NIFRT group was not equivalent, suggesting a role for locoregional therapies in selected patients with ROC. PMID- 26825831 TI - Tubal Ligation and Risk of Endometrial Cancer: Findings From the Women's Health Initiative. AB - OBJECTIVE: Bilateral tubal ligation (BTL) is a common form of birth control in the United States. There are limited, contradictory data examining BTL and the risk of endometrial cancer and none examining type I and type II cancers separately. We investigated the association between BTL and endometrial cancer risk using the Women's Health Initiative (WHI) Observational and Dietary Modification Studies. METHODS: Demographic information and history of BTL were obtained from the baseline questionnaires from 76,483 WHI participants in the Observational and Dietary Modification Studies. Univariable and multivariable models were used to examine the association of BTL with type I and type II endometrial cancers. RESULTS: A total of 1137 women were diagnosed with incident endometrial cancer (972 type I and 128 type II) during a mean follow-up of 11.3 years. Overall, 14,499 (19%) women had undergone BTL. There were no statistically significant associations noted between BTL and age at BTL for type I or type II cancers. CONCLUSIONS: We examined the largest patient cohort to date in an effort to determine the impact of BTL on endometrial cancer risk. In the WHI trial, we observed no overall effect of BTL on the risk of type I or type II endometrial cancer, suggesting that patients undergoing this popular birth control method likely do not have an associated change in their baseline risk for endometrial cancer. PMID- 26825833 TI - Prognostic Factors in Adult Granulosa Cell Tumor: A Long Follow-Up at a Single Center. AB - OBJECTIVE: In this study, we aimed to demonstrate characteristics, recurrence rates, survival numbers, and factors associated with survival of patients with adult granulosa cell tumor (AGCT) from a single institution. Our secondary goal was to evaluate the necessity of staging surgery and the importance of a comprehensive lymphadenectomy in these patients. METHODS: The data of 158 patients in our institution who were diagnosed with AGCT between 1988 and 2013 were evaluated. The data were obtained from the files of the patients, electronic database of the gynecologic oncology clinic, operation notes, and pathology records. RESULTS: The median (range) age of the patients was 50.3 (22-82) years. The main symptom was postmenopausal bleeding (25.9%). Seventy-six percent of the patients underwent staging surgery including lymphadenectomy. Among these patients, 3 (2.5%) had lymph node metastasis. The median (range) follow-up time was 97 (1-296) months. In the follow-up period, 18 patients (12.5%) had recurrence. Menopausal status (P = 0.016), advanced age (P = 0.024), cyst rupture (P = 0.001), poorly differentiated tumor (P = 0.002), and advanced stage (P < 0.001) were associated with recurrence. Stage was the only independent prognostic factor for the development of recurrence. None of the patients had lymph node failure. CONCLUSIONS: In the present study with a long follow-up period and in which most of the patients had staging surgery including lymphadenectomy (76.6%), lymph node recurrence was not observed and the total recurrence rate (12.5%) was lower than that reported in the literature. The study showed the importance of surgical staging in patients with AGCT. PMID- 26825834 TI - Patterns of Care, Predictors, and Outcomes of Adjuvant Therapy for Early- and Advanced-Stage Uterine Clear Cell Carcinoma: A Population-Based Analysis. AB - OBJECTIVE: The aim of the study was to examine the patterns of care and the impact of chemotherapy and radiation on survival in women diagnosed with uterine clear cell carcinoma (UCCC). The primary outcomes of this analysis were receipt of treatment within 6 months of diagnosis and overall survival. METHODS AND MATERIALS: Women diagnosed with UCCC from 2003 to 2011 were identified through the National Cancer Data Base. Standard univariate and multivariable analyses with logistic regression were performed. Kaplan-Meier survival analysis was used to generate overall survival data. Factors predictive of outcome were evaluated using the log-rank test and Cox proportional hazards model. RESULTS: A total of 3212 patients were identified. Chemotherapy, radiation, and combination chemotherapy and radiation were administered in 23.3%, 19.7%, and 11.1% of women, respectively. After adjusting for age, race, socioeconomic status, facility type, stage, surgery, lymph node dissection, comorbidity index, period of diagnosis, and registry location, there was an association between combined chemotherapy and radiation (hazard ratio, 0.74; 95% confidence interval, 0.61-0.90) with improved survival. Adjuvant therapy was not associated with improved survival among patients with early-stage disease (stages I and II). Both chemotherapy and combined chemotherapy and radiation were associated with significantly improved survival among patients with advanced-stage disease (stages III and IV). CONCLUSIONS: In patients with early-stage UCCC, adjuvant therapy was not associated with significantly improved survival. Chemotherapy and combination of chemotherapy and radiation were associated with improved survival in patients with advanced-stage UCCC. PMID- 26825835 TI - Surgical Outcomes of Patients Undergoing Extrafascial Hysterectomy After Neoadjuvant Radiotherapy With or Without Chemotherapy for Locally Advanced Endometrial Cancer Clinically Extending to the Cervix or Parametria. AB - OBJECTIVES: Recent data have shown high rates of clinical and pathologic responses to neoadjuvant radiation therapy for locally advanced endometrial cancer. There are limited data on the surgical outcomes of these patients in the era of modern radiation and surgical techniques. We sought to characterize surgical outcomes after extrafascial hysterectomy in this population. METHODS: Patients with endometrial cancer of all histologies clinically involving the cervix or parametria treated with neoadjuvant brachytherapy followed by extrafascial hysterectomy from 1999 to 2014 were identified. Patient charts were reviewed for data regarding treatment characteristics and postoperative outcomes. Pearson chi and logistic regression analyses were used to assess correlations between surgical complications and treatment-related variables. RESULTS: Twenty nine patients met inclusion criteria. Mean operating time for the cohort was 115 minutes. Mean estimated blood loss was 100 mL. No visceral injuries occurred. Mean length of hospital stay was 1 and 4 days for the minimally invasive and laparotomy groups, respectively. Rates of postoperative ileus, blood transfusion, wound infection, and readmission were 3%, 3%, 6%, and 3%, respectively. No case of prolonged urodynamic dysfunction was noted. The rate of vaginal complications was significantly higher in the group of patients who underwent minimally invasive surgery as compared with laparotomy (33% vs 5%, P < 0.041). CONCLUSIONS: These data support adjuvant extrafascial hysterectomy after neoadjuvant radiotherapy for endometrial cancer with cervical or parametrial involvement as a safe and viable procedure, with low rates of postoperative complications. Extra care should be taken when closing the vaginal cuff to reduce the risk of vaginal cuff complications. PMID- 26825836 TI - Matrix Metallopeptidase 14 Plays an Important Role in Regulating Tumorigenic Gene Expression and Invasion Ability of HeLa Cells. AB - OBJECTIVES: The objectives of this study were to investigate the functional effect of matrix metallopeptidase 14 (MMP14) on cell invasion in cervical cancer cells (HeLa line) and to study the underlying molecular mechanisms. METHODS: Expression vector of short hairpin RNA targeting MMP14 was treated in HeLa cells, and then, transfection efficiency was verified by a florescence microscope. Transwell assay was used to investigate cell invasion ability in HeLa cells. Quantitative polymerase chain reaction and Western blotting analysis were used to detect the expression of MMP14 and relative factors in messenger RNA and protein levels, respectively. RESULTS: Matrix metallopeptidase 14 short hairpin RNA expression vector transfection obviously decreased MMP14 expression in messenger RNA and protein levels. Down-regulation of MMP14 suppressed invasion ability of HeLa cells and reduced transforming growth factor beta1 and vascular endothelial growth factor B expressions. Furthermore, MMP14 knockdown decreased bone sialoprotein and enhanced forkhead box protein L2 expression in both RNA and protein levels. CONCLUSION: Matrix metallopeptidase 14 plays an important role in regulating invasion of HeLa cells. Matrix metallopeptidase 14 knockdown contributes to attenuating the malignant phenotype of cervical cancer cell. PMID- 26825837 TI - Utilization and Role of Adjuvant Radiotherapy and Chemotherapy for Uterine Clear Cell Carcinoma: A National Cancer Data Base Analysis. AB - OBJECTIVE: Because of the rarity of uterine clear cell carcinoma (UCCC), a National Cancer Data Base analysis was conducted to evaluate practice patterns and implications of adjuvant therapy. METHODS: The National Cancer Data Base was queried for UCCC patients diagnosed from 1998 to 2011. Patients receiving neoadjuvant therapy, lacking surgical staging, or having follow-up time shorter than 6 months were excluded. Factors associated with utilization were assessed using logistic regression. To define the probability of receiving chemotherapy and radiotherapy (CT + RT), propensity scores with inverse probability of treatment weighting (IPTW) were calculated using multivariable logistic regression. Log-rank test and multivariable IPTW-adjusted Cox proportional hazards modeling were then conducted. RESULTS: A total of 2504 patients were identified, with a median follow-up of 65.5 months. Most patients had FIGO (International Federation of Gynecology and Obstetrics) stage I to II UCCC (71.4%). Adjuvant RT alone, CT alone, or CT + RT was given in 35.3%, 9.5%, and 11.7%, respectively. Among those receiving RT, external beam was the most common modality (69.4%). Later year of diagnosis (>2005: odds ratio [OR], 4.42; 95% confidence interval [95% CI], 2.44-8.01), higher FIGO stage (IIIA-IIIC2: OR, 6.34; 95% CI, 3.93-10.24), larger tumor size (3.6-5.0 cm: OR, 3.40; 95% CI, 1.76 6.55), and lymph node dissection (OR, 4.22; 95% CI, 1.60-11.15) were associated with a higher chance of receiving CT + RT. With IPTW-adjusted multivariable analysis, CT + RT significantly decreased mortality risk in stage III to IVA patients (hazards ratio, 0.41; 95% CI, 0.22-0.77), trending toward benefit in stage I to II patients (hazards ratio, 0.53; 95% CI, 0.27-1.07). CONCLUSIONS: In this hospital-based registry analysis of UCCC, adjuvant CT + RT significantly reduced the risk of death, reaching statistical significance for stage III to IVA patients. PMID- 26825838 TI - Improved Postoperative Pain Control for Cytoreductive Surgery in Women With Ovarian Cancer Using Patient-Controlled Epidural Analgesia. AB - OBJECTIVE: Many studies have compared different methods of postoperative pain management in abdominal laparotomy patients; however, the conclusions have been inconsistent and controversial. This study aimed to compare the pain scores and complications of patients who underwent cytoreductive surgery for ovarian cancer and used either patient-controlled epidural analgesia (PCEA) or patient controlled intravenous analgesia (PCA) for postoperative pain management. We hypothesized that PCEA would be superior to PCA for postoperative pain management in ovarian cancer surgery. MATERIALS AND METHODS: The medical records of women who underwent ovarian cancer surgery in 2014 were reviewed retrospectively. Pain scores for postoperative days (PODs) 0 to 5 days and the incidence of complications were examined and compared in patients who received PCEA and PCA. Means were compared using an independent sample t test or Wilcoxon rank sum test, and proportions were compared using Fisher exact test or a chi(2) test at each time point. A mixed-effects model was applied to determine correlations among repeated measurements. A P value less than 0.05 was considered significant. RESULTS: Of the 105 study patients, 38 received PCEA and 67 received PCA. Pain scores were significantly lower in the PCEA group than the PCA group at POD 0 (2.47 +/- 1.75 vs 4.39 +/- 1.17; P < 0.001), 1 (2.65 +/- 1.02 vs 3.32 +/- 1.09; P < 0.001), and 3 (2.17 +/- 1.13 vs 2.79 +/- 1.08; P = 0.011), and tended to be lower in the PCEA group at PODs 2, 4, and 5. Patient-controlled epidural analgesia provided significantly better pain relief as analyzed by a mixed-effect model. Complications were not significantly different between both groups. There was no significant difference in pain relief between both groups at PODs 4 and 5. CONCLUSIONS: Patient-controlled epidural analgesia was more effective for postoperative pain management compared with PCA from POD 0 to POD 3 in patients with ovarian cancer who underwent cytoreductive surgery, without increasing the morbidity. PMID- 26825839 TI - Predictors of Survival in Patients With FIGO Stage IVB Cervical Cancer. AB - OBJECTIVE: The aim of this study was to identify prognostic factors and establish a model for predicting life expectancy in International Federation of Gynecology and Obstetrics stage IVB cervical cancer patients. METHODS: The baseline characteristics and outcome data of patients with stage IVB cervical cancer between May 1994 and October 2014 were collected and retrospectively reviewed. A Cox proportional hazards regression model was used to identify independent predictors of survival in stage IVB cervical cancer patients. RESULTS: A total of 107 patients were included in our database. The median overall survival (OS) period was 16 months. Multivariate analysis revealed that the metastatic site (hazards ratio, 3.09; 95% confidence interval, 1.94-4.88; P < 0.0001) and a white blood cell (WBC) count exceeding 10,000/MUL (hazards ratio, 2.02; 95% confidence interval, 1.19-3.30; P = 0.0102) were significant prognostic factors in terms of OS. Patient survival was inversely correlated with the number of these prognostic factors possessed. When the patients were divided into 3 prognostic groups, the median OS of the patients with 0, 1, or 2 poor prognostic factors was 26, 12, and 7 months, respectively. Among the patients with WBC counts of less than 10,000/MUL, treatment with radiotherapy resulted in improved survival compared with chemotherapy or palliative care alone. In contrast, radiotherapy had minimal effects on survival in patients with WBC counts of greater than 10,000/MUL. CONCLUSIONS: The metastatic site and an elevated WBC count are significant prognostic factors in patients with stage IVB cervical cancer. Our prognostic model composed of these 2 clinical variables might enable physicians to predict survival more accurately. PMID- 26825840 TI - An Assessment of Prognostic Factors, Adjuvant Treatment, and Outcomes of Stage IA Polyp-Limited Versus Endometrium-Limited Type II Endometrial Carcinoma. AB - OBJECTIVE: To determine clinical outcomes in patients with stage IA polyp-limited versus endometrium-limited high-grade (type II) endometrial carcinoma (EC). METHODS: We identified all cases of stage IA polyp-limited or endometrium-limited high-grade EC (FIGO grade 3 endometrioid, serous, clear cell, or mixed) who underwent simple hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, omental biopsy, and pelvic and para-aortic lymph node dissection and received adjuvant treatment at our institution from October 1995 to November 2012. Progression-free survival (PFS) and overall survival (OS) by histology, adjuvant therapy, and polyp-limited versus endometrium-limited disease status were determined using log-rank test. We analyzed 3 treatment groups: patients who received chemotherapy with or without radiation therapy (RT) (intravaginal or pelvic); patients who received RT (intravaginal RT or pelvic RT) alone; and patients who received no adjuvant treatment. RESULTS: In all, 85 women underwent hysterectomy/salpingo-oophorectomy; all were surgically staged with lymph node assessment and had stage IA EC with no lymphovascular or myometrial invasion. Median follow-up for survivors was 46.5 months (range, 1.98-188.8 months). Forty nine patients (57.6%) had polyp-limited disease, and 36 (42.4%) had endometrium limited disease. There were no significant differences in clinicopathologic characteristics between patients within the 3 treatment groups with regard to age at diagnosis, mean body mass index, ECOG (Eastern Cooperative Oncology Group) performance status, polyp-limited or endometrium-limited disease, diabetes, or race. The 3-year PFS rate was 94.9% and the 3-year OS rate was 98.8%. Univariate PFS and OS analysis revealed that age was a relevant prognostic factor (PFS hazard ratio [95% confidence interval], 1.13 [1.02-1.25]; P = 0.022; OS hazard ratio [95% confidence interval], 1.19 [1.02-1.38]; P = 0.03). Adjuvant treatment did not impact outcomes. CONCLUSIONS: Clinical outcomes of surgical stage IA type II polyp- or endometrium-limited high-grade epithelial EC are equally favorable regardless of histologic subtype or adjuvant therapy received. The benefit of adjuvant therapy in this select group remains to be determined. PMID- 26825841 TI - Therapeutic Dilemma: Prognostic Factors and Outcome for Neuroendocrine Tumors of the Cervix. AB - OBJECTIVES: The aim of this study was to review treatment and outcomes for neuroendocrine tumors (NETs) of the cervix at a National Cancer Institute designated Comprehensive Cancer Center. MATERIALS AND METHODS: Data for women with NET of the cervix treated at our institution, since 1999, were collected. Progression-free survival (PFS) and overall survival (OS) were assessed with respect to age, tumor size, tobacco use, lymph node status, stage of disease, and type of treatment. RESULTS: Among 18 patients (median age, 44 years), 9 (50%) had tumors larger than 5 cm and advanced-stage disease (IB2-IV). Seven recurrences were noted (39%). Median PFS was not reached, and median OS was 72.2 months. Surgery was the only factor significantly associated with both PFS and OS (3-year PFS, 90% vs 30%, P = 0.01; 3-year OS: 89% vs 18%, P = 0.019). Age 40 years or younger and absence of lymph node metastases correlated significantly with PFS, with a trend toward improved OS. Recurrences were less likely with stage IA to IB1 compared with stages IB2 to IVA and IVB (hazards ratio, 0.33; P = 0.054), with median OS of 72.2, 19.2, and 7.4 months, respectively (P = 0.002). Although patients with tumors 4 cm or smaller had better outcomes, this factor did not reach statistical significance. Chemotherapy, radiation therapy, and tobacco use were not associated with survival. CONCLUSIONS: Neuroendocrine tumors of the cervix present at a relatively young age, with bulky tumors and advanced-stage disease. Surgery, younger age, smaller tumor size, early stage, and absence of lymph node involvement seem to be associated with improved survival. Nonetheless, optimal management is yet to be determined, and multimodality treatment is advocated. PMID- 26825842 TI - Robotic Surgery in Patients With Locally Advanced Cervical Cancer After Neoadjuvant Chemotherapy: Survival Outcomes. AB - AIM: To evaluate the survival outcomes of consecutive patients with locally advanced cervical cancer (LACC) who underwent comprehensive robotic surgery after neoadjuvant chemotherapy (NACT). MATERIALS AND METHODS: Since 2009, patients with LACC (FIGO [International Federation of Gynecology and Obstetrics] stages IB2 IIB) were submitted to robotic surgical staging after 3 cycles of NACT. Clinical objective tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, whereas pathologic responses were defined according to the criteria of the European study SNAP01. Univariable and multivariable analyses were performed to assess potential clinicopathologic prognostic factors affecting progression-free survival and overall survival (OS). RESULTS: During the study period, 32 patients meeting the inclusion criteria were managed. The median (range) age and body mass index were 47.3 (8.6-75.5) years and 22.7 (17.5-37.1) kg/m(2), respectively. Overall, 28.0 (range, 12-58) lymph nodes were retrieved. According to the final pathologic examination, 6 (18.8%) women had positive pelvic lymph nodes, whereas 16 (50.0%) patients achieved an optimal pathological response. After a median follow-up of 36.3 (range, 5.2-71.1) months, 6 (18.8%) patients had a recurrence and subsequently died of disease.Positive nodal status was the only independent predictor of both progression-free survival (12.5 [2.3 69.1]; P < 0.0001) and OS (12.0 [2.0-60.4]; P < 0.0001) at multivariable analysis. CONCLUSIONS: Nodal status represents the strongest predictor of survival in women with LACC. Similarly, NACT including 3 agents (TIP [paclitaxel 175 mg/m(2) + ifosfamide 5 g/m(2) + cisplatin 75 mg/m(2)] and TEP [paclitaxel 175 mg/m(2) + epirubicin 80 mg/m(2) + cisplatin 75 mg/m(2)] regimens) warranted better OS than those achieved by other schedules. PMID- 26825843 TI - Screening for Nonalcoholic Steatohepatitis in Individuals with Type 2 Diabetes: A Cost-Effectiveness Analysis. AB - BACKGROUND AND AIM: Individuals with type 2 diabetes are at heightened risk for nonalcoholic fatty liver disease, which gives rise to nonalcoholic steatohepatitis (NASH) and cirrhosis. Yet, current guidelines do not recommend screening for NASH among these high-risk patients. Using a simulation model, we assessed the effectiveness and cost-effectiveness of screening diabetic patients for NASH. METHODS: A Markov model was constructed to compare two management strategies for 50-year-olds with diabetes. In the No Screening strategy, patients do not undergo screening, although NASH may be diagnosed incidentally over their lifetime. In the NASH Screening strategy, all patients receive a one-time screening ultrasound. Individuals with fatty infiltration on ultrasound then have a liver biopsy, and those found to have NASH receive medical therapy, which decreases progression to cirrhosis. Endpoints evaluated included quality-adjusted life years (QALYs) gained, costs, and incremental cost-effectiveness ratios (ICERs). RESULTS: Screening for NASH decreased the number of individuals who developed cirrhosis by 12.9 % and resulted in an 11.9 % decrease in liver-related deaths. However, screening resulted in 0.02 fewer QALYs, due to the disutility associated with treatment, and was therefore dominated by the No Screening strategy. When the model excluded this quality-of-life decrement, screening became cost-effective, at an ICER of $42,134 per QALY. CONCLUSIONS: Screening for NASH may improve liver-related outcomes, but is not cost-effective at present, due to side effects of therapy. As better tolerated treatments for NASH become available, even with modest efficacy, screening for NASH will become cost effective. PMID- 26825844 TI - Efficacy and Safety of Propofol-Mediated Sedation for Outpatient Endoscopic Retrograde Cholangiopancreatography (ERCP). AB - BACKGROUND AND AIMS: Propofol sedation for endoscopy may result in a rapid and unpredictable progression from deep sedation to general anesthesia, leading to potential complications. We investigated the incidence and predictors of sedation related adverse events (SAEs) in nonintubated patients who underwent outpatient ERCP procedures with propofol sedation. METHODS: We conducted a retrospective study of patients who underwent propofol sedation for ERCP procedures. Patients were sedated using propofol in combination with low-dose opiates. Data collected included patient demographics, American Society of Anesthesiologists (ASAs) physical status, and procedure times. SAE includes hypoxia (pulse oximetry <90 %), hypotension (systolic blood pressure <90 mmHg), and conversation to endotracheal intubation. Factors associated with SAEs were examined by univariate analysis and multivariate regression analysis (MVA). RESULTS: A total of 3041 patients were evaluated. The median BMI was 25.2 kg/m(2), and the median ASA score was 3. The mean (+/-SD) duration of the procedures was 59 +/- 23 min. Hypoxia requiring airway manipulation occurred in 28 % (n = 843) patients and hypotension requiring vasopressors in 0.4 % (n = 12). Forty-nine (1.6 %) patients required endotracheal intubation as a result of food in the stomach. Procedures underwent early termination in 8 (0.3 %) cases due to sedation-related hypotension (n = 5) and refractory laryngospasm (n = 3). Six patients were admitted after the ERCP for aspiration pneumonia as a result of sedation. Patients who developed SAE were older, had a higher mean BMI, and had longer mean procedure durations. On MVA, older age (p = 0.003), female sex (p = 0.001), BMI (p = 0.02), and ASA class >=3 (p = 0.01) independently predicted SAEs. CONCLUSIONS: Propofol can be used safely and effectively as a sedative agent for patients undergoing ERCPs when administered by trained professionals. Age, female sex, BMI, and ASA class >=3 are independent predictors of SAEs. PMID- 26825845 TI - An Untapped Resource: Left Renal Vein Interposition Graft for Portal Vein Reconstruction During Pancreaticoduodenectomy. PMID- 26825846 TI - Piotr P. Slonimski - The Warrior Pope: The discovery of mitochondrial (petite) mutants and split genes. PMID- 26825847 TI - Flagging performance of the Sysmex XN2000 haematology analyser. AB - INTRODUCTION: With the introduction of the Sysmex XN haematology analyser, the white blood cell differentiation channel (WDF) and abnormal cell detection channel (WPC) have been added with algorithms for flagging blasts and abnormal or atypical lymphocytes. METHODS: In this study, 2011 samples were evaluated on a Sysmex XN2000 analyser and microscopically reviewed using a CellaVision DM96 digital microscope. RESULTS: A reference group of apparently healthy blood donors (n = 262) demonstrated in only three samples a positive suspect flag, which could not be confirmed microscopically. Positive WBC suspect flags were demonstrated in 3% of the 2011 samples. From the 55 samples with positive WBC suspect flags, an automatic reflex test was performed within the WPC. The WPC reflex test resulted in 10* Blast?, 15* Abnormal lymph? and 15* Atypical lymph? flags, which could be confirmed microscopically in 33% of these cases. A negative flagging was demonstrated in 15 cases. Microscopic evaluation demonstrated no abnormalities in these 15 cases. However, laboratory technicians also reported the presence of abnormal lymphocytes in 158 samples without an Abnormal lymph? flag. CONCLUSION: In conclusion, the combined use of WDF and WPC resulted in a reduction of approximately 25% of the number blood smears. As a result of the various techniques for light microscopy and haemocytometry, the adequacy of the XN flagging for abnormal and atypical lymphocytes cannot be established with certainty. To improve the quality of the reported results, it is recommended that laboratory technicians incorporate the haemocytometry results and the flagging information in the microscopic slide review. PMID- 26825848 TI - Drug screening and grouping by sensitivity with a panel of primary cultured cancer spheroids derived from endometrial cancer. AB - Several molecular targeting drugs are being evaluated for endometrial cancer; selecting patients whose cancers are sensitive to these agents is of paramount importance. Previously, we developed the cancer tissue-originated spheroid method for primary cancer cells taken from patients' tumors as well as patient-derived xenografts. In this study, we successfully prepared and cultured cancer tissue originated spheroids from endometrial cancers. Characteristics of the original tumors were well retained in cancer tissue-originated spheroids including morphology and expression of p53 or neuroendocrine markers. We screened 79 molecular targeting drugs using two cancer tissue-originated spheroid lines derived from endometrioid adenocarcinoma grade 3 and serous adenocarcinoma. Among several hits, we focused on everolimus, a mammalian target of rapamycin complex 1 inhibitor, and YM155, a survivin inhibitor. When sensitivity to everolimus or YM155 was assessed in 12 or 11 cancer tissue-originated spheroids, respectively, from different endometrial cancer patients, the sensitivity varied substantially. The cancer tissue-originated spheroids sensitive to everolimus showed remarkable suppression of proliferation. The phosphorylation status of the mammalian target of rapamycin complex 1 downstream molecules before and after everolimus treatment did not predict the effect of the drug. In contrast, the cancer tissue-originated spheroids sensitive to YM155 showed remarkable cell death. The effect of YM155 was also confirmed in vivo. The histological type correlated with YM155 sensitivity; non-endometrioid adenocarcinomas were sensitive and endometrioid adenocarcinomas were resistant. Non-canonical autophagic cell death was the most likely cause of cell death in a sensitive cancer tissue-originated spheroid. Thus, sensitivity assays using cancer tissue-originated spheroids from endometrial cancers may be useful for screening drugs and finding biomarkers. PMID- 26825849 TI - Characterization of release profile of ornithine carbamoyltransferase from primary rat hepatocytes treated with hepatotoxic drugs: Implications for its unique potential as a drug-induced liver injury biomarker. AB - Ornithine carbamoyltransferase (OCT) is a mitochondrial protein expressed primarily in the liver. It has been shown that, like alanine aminotransferase (ALT), OCT is released from damaged hepatocytes in rats and humans, which has given rise to the possibility that OCT might provide a diagnostic biomarker of various forms of liver damage, including drug-induced liver injury (DILI). However, OCT release characteristics in DILI, as well as their diagnostic advantages, remain elusive. Therefore, this study aimed at clarifying whether and how OCT is released from rat primary hepatocytes in vitro using seven potentially hepatotoxic drugs. The results showed that OCT releases from damaged hepatocytes were observed for all tested drugs, and that those releases were not associated with mitochondrial membrane proteins. It should be underscored that the release dynamics were significantly larger than those of ALT. Furthermore, unlike ALT, the maximum OCT release levels showed differences depending on the drug being tested, suggesting that OCT release was susceptible to toxicity mechanisms. Taken together, these unique release characteristics highlight the possibility that OCT could provide a promising DILI biomarker that might contribute not only to diagnostic accuracy improvements, but also to a better understanding of toxicity types in clinical and drug development settings. PMID- 26825850 TI - The population genetics of pharmacogenomics VIP variants in the Sherpa population. AB - Polymorphic distributions of pharmacogenes among some ethnicities are under represented in current pharmacogenetic research. Particularly, there is a paucity of pharmacogenetic information in the Sherpa population in Tibet. We used the Sequenom MassARRAY single nucleotide polymorphism (SNP) genotyping technology to detect 86 very important pharmacogene (VIP) variants in Sherpas and compared the genotypic frequencies of these variants with HapMap populations. Overall, 59 of the 60 previously reported variants in the HapMap populations were found in our study. We found minimal differences between populations of Sherpas and Chinese Han in Beijing (CHB), Chinese in Metropolitan Denver, Colorado (CHD), Japanese in Tokyo, Japan (JPT), and Mexicans in Los Angeles, California (MEX) after a strict Bonferroni correction. Only 8, 4, 5, 4 VIP genotypes, respectively, were different in these groups. Additionally, pairwise FST values and clustering analyses showed that the VIP variants in the Sherpa population exhibited a close genetic affinity with the CHB and JPT populations, but they were most similar to the CHD population. Our results contribute to a better understanding of the molecular basis underlying ethnic differences in drug response, which may potentially benefit the development of personalized medicine for the Sherpa population. PMID- 26825851 TI - Influence of high glucose state on bromopyruvate-induced cytotoxity by human colon cancer cell lines. AB - BACKGROUND: Attention must be paid to chemotherapy for cancer patients in a hyperglycemia state. It is difficult for chemotherapy to cure cancer in patients in a hyperglycemia state. This study was carried out to determine the change in cell viability after treatment with bromopyruvate, which is an alkylating drug with anti-tumor activity, in a high glucose condition. METHODS: The function of l lactate and bromopyruvate transport was studied using human colon cancer cell lines (LoVo and HT-29) and radiolabeled l-lactate and bromopyruvate. Cell viability was monitored by the trypan blue exclusion assay. The expression level of human monocarboxylate transporter 1 (hMCT1) was evaluated by Western blot analysis. RESULTS: Bromopyruvate-induced cell death was suppressed by a high glucose condition. l-Lactate and bromopyruvate uptake were suppressed by a high glucose condition. hMCT1 as a bromopyruvate carrier was functionally expressed in the cells. However, the expression of hMCT1 was suppressed by a high glucose state. CONCLUSIONS: Down-regulation of hMCT1 by a high glucose state is one of the possibilities of the bromopyruvate resistance. We should pay scrupulous attention to cancer chemotherapy for patients who have developed diabetes. PMID- 26825852 TI - Baleen wear reveals intraoral water flow patterns of mysticete filter feeding. AB - A survey of macroscopic and microscopic wear patterns in the baleen of eight whale species (Cetacea: Mysticeti) discloses structural, functional, and life history properties of this neomorphic keratinous tissue, including evidence of intraoral water flow patterns involved in filter feeding. All baleen demonstrates wear, particularly on its medial and ventral edges, as flat outer layers of cortical keratin erode to reveal horn tubes, also of keratin, which emerge as hair-like fringes. This study quantified five additional categories of specific wear: pitting of plates, scratching of plates, scuffing of fringes, shortening of fringes, and reorientation of fringes (including fringes directed between plates to the exterior of the mouth). Blue whale baleen showed the most pitting and sei whale baleen the most scratching; gray whale baleen had the most fringe wear. The location of worn baleen within the mouth suggests that direct contact with the tongue is not responsible for most wear, and that flowing water as well as abrasive prey or sediment carried by the flowing water likely causes pitting and scratching of plates as well as fringe fraying, scuffing, shortening, and reorientation. Baleen also has elevated vertical and horizontal ridges that are unrelated to wear; these are probably related to growth and may allow for age determination. PMID- 26825854 TI - Treatment with the MAO-A inhibitor clorgyline elevates monoamine neurotransmitter levels and improves affective phenotypes in a mouse model of Huntington disease. AB - Abnormal monoamine oxidase A and B (MAO-A/B) activity and an imbalance in monoamine neurotransmitters have been suggested to underlie the pathobiology of depression, a major psychiatric symptom observed in patients with neurodegenerative diseases, such as Huntington disease (HD). Increased MAO-A/B activity has been observed in brain tissue from patients with HD and in human and rodent HD neural cells. Using the YAC128 mouse model of HD, we studied the effect of an irreversible MAO-A inhibitor, clorgyline, on the levels of select monoamine neurotransmitters associated with affective function. We observed a decrease in striatal levels of the MAO-A/B substrates, dopamine and norepinephrine, in YAC128 HD mice compared with wild-type mice, which was accompanied by increased anxiety- and depressive-like behaviour at five months of age. Treatment for 26 days with clorgyline restored dopamine, serotonin, and norepinephrine neurotransmitter levels in the striatum and reduced anxiety- and depressive-like behaviour in YAC128 HD mice. This study supports a potential therapeutic use for MAO-A inhibitors in the treatment of depression and anxiety in patients with HD. PMID- 26825853 TI - Treatment of retinitis pigmentosa due to MERTK mutations by ocular subretinal injection of adeno-associated virus gene vector: results of a phase I trial. AB - MERTK is an essential component of the signaling network that controls phagocytosis in retinal pigment epithelium (RPE), the loss of which results in photoreceptor degeneration. Previous proof-of-concept studies have demonstrated the efficacy of gene therapy using human MERTK (hMERTK) packaged into adeno associated virus (AAV2) in treating RCS rats and mice with MERTK deficiency. The purpose of this study was to assess the safety of gene transfer via subretinal administration of rAAV2-VMD2-hMERTK in subjects with MERTK-associated retinitis pigmentosa (RP). After a preclinical phase confirming the safety of the study vector in monkeys, six patients (aged 14 to 54, mean 33.3 years) with MERTK related RP and baseline visual acuity (VA) ranging from 20/50 to <20/6400 were entered in a phase I open-label, dose-escalation trial. One eye of each patient (the worse-seeing eye in five subjects) received a submacular injection of the viral vector, first at a dose of 150 ul (5.96 * 10(10)vg; 2 patients) and then 450 ul (17.88 * 10(10)vg; 4 patients). Patients were followed daily for 10 days at 30, 60, 90, 180, 270, 365, 540, and 730 days post-injection. Collected data included (1) full ophthalmologic examination including best-corrected VA, intraocular pressure, color fundus photographs, macular spectral domain optical coherence tomography and full-field stimulus threshold test (FST) in both the study and fellow eyes; (2) systemic safety data including CBC, liver and kidney function tests, coagulation profiles, urine analysis, AAV antibody titers, peripheral blood PCR and ASR measurement; and (3) listing of ophthalmological or systemic adverse effects. All patients completed the 2-year follow-up. Subretinal injection of rAAV2-VMD2-hMERTK was associated with acceptable ocular and systemic safety profiles based on 2-year follow-up. None of the patients developed complications that could be attributed to the gene vector with certainty. Postoperatively, one patient developed filamentary keratitis, and two patients developed progressive cataract. Of these two patients, one also developed transient subfoveal fluid after the injection as well as monocular oscillopsia. Two patients developed a rise in AAV antibodies, but neither patient was positive for rAAV vector genomes via PCR. Three patients also displayed measurable improved visual acuity in the treated eye following surgery, although the improvement was lost by 2 years in two of these patients. Gene therapy for MERTK related RP using careful subretinal injection of rAAV2-VMD2-hMERTK is not associated with major side effects and may result in clinical improvement in a subset of patients. PMID- 26825855 TI - Assessing sample representativeness in randomized controlled trials: application to the National Institute of Drug Abuse Clinical Trials Network. AB - AIMS: To compare the characteristics of individuals participating in randomized controlled trials (RCTs) of treatments of substance use disorder (SUD) with individuals receiving treatment in usual care settings, and to provide a summary quantitative measure of differences between characteristics of these two groups of individuals using propensity score methods. Design Analyses using data from RCT samples from the National Institute of Drug Abuse Clinical Trials Network (CTN) and target populations of patients drawn from the Treatment Episodes Data Set-Admissions (TEDS-A). Settings Multiple clinical trial sites and nation-wide usual SUD treatment settings in the United States. PARTICIPANTS: A total of 3592 individuals from 10 CTN samples and 1 602 226 individuals selected from TEDS-A between 2001 and 2009. Measurements The propensity scores for enrolling in the RCTs were computed based on the following nine observable characteristics: sex, race/ethnicity, age, education, employment status, marital status, admission to treatment through criminal justice, intravenous drug use and the number of prior treatments. Findings The proportion of those with >= 12 years of education and the proportion of those who had full-time jobs were significantly higher among RCT samples than among target populations (in seven and nine trials, respectively, at P < 0.001). The pooled difference in the mean propensity scores between the RCTs and the target population was 1.54 standard deviations and was statistically significant at P < 0.001. CONCLUSIONS: In the United States, individuals recruited into randomized controlled trials of substance use disorder treatments appear to be very different from individuals receiving treatment in usual care settings. Notably, RCT participants tend to have more years of education and a greater likelihood of full-time work compared with people receiving care in usual care settings. PMID- 26825856 TI - Survival outcomes of combined external beam radiotherapy and brachytherapy vs. brachytherapy alone for intermediate-risk prostate cancer patients using the National Cancer Data Base. AB - PURPOSE: The purpose was to evaluate survival outcomes between external beam radiotherapy (EBRT) plus brachytherapy and brachytherapy alone for intermediate risk prostate cancer, using the National Cancer Data Base. METHODS AND MATERIALS: The National Cancer Data Base was queried for cN0M0 intermediate-risk patients treated from 2004 to 2006, with available data for Gleason score (GS), prostate specific antigen (PSA), tumor stage, and receipt of radiation therapy (RT) and androgen deprivation therapy. RT comparison groups were the following: EBRT (40 50.4 Gy) plus brachytherapy and brachytherapy alone. RESULTS: A total of 10,571 patients were included: 3,148 received EBRT plus brachytherapy and 7,423 received brachytherapy alone. Median followup was 84 months (2-122 months); median age was 68 years (40-90 years). Unadjusted 5- and 7-year overall survival (OS) rates between EBRT plus brachytherapy vs. brachytherapy alone were 91.4% vs. 90.2% and 85.7% vs. 82.9%, respectively (p < 0.001). EBRT plus brachytherapy was associated with longer OS compared with brachytherapy alone under multivariate (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.75-0.93; p = 0.001) and propensity score-matched analyses (HR, 0.85; 95% CI, 0.75-0.97; p = 0.006). Further subset analysis performed based on the Radiation Therapy Oncology Group 0232 inclusion criteria (GS 7 if PSA < 10 or GS < 7 if PSA 10-20) also demonstrated longer OS with EBRT plus brachytherapy (HR, 0.87; 95% CI, 0.77-0.98; p = 0.026). CONCLUSIONS: EBRT plus brachytherapy is associated with a modest OS improvement compared with brachytherapy alone in this population-based analysis. Although this benefit appears statistically significant, the relatively small difference in OS raises the question of overall clinical benefit with combined modality RT for intermediate-risk prostate cancer, given the potential increased risk for toxicities. Future results from Radiation Therapy Oncology Group 0232 should provide further insight on this topic. PMID- 26825857 TI - High- and low-dose-rate intraoperative radiotherapy for thoracic malignancies resected with close or positive margins. AB - PURPOSE: Local recurrence is a significant problem after surgical resection of thoracic tumors. As intraoperative radiotherapy (IORT) can deliver radiation directly to the threatened margin, we have used this therapy in an attempt to reduce local recurrence, using high-dose-rate (HDR) as well as low-dose-rate (LDR) techniques. METHODS AND MATERIALS: We performed a retrospective review of patients undergoing LDR ((125)I) mesh placement or HDR ((192)Ir) afterloading therapy during lung tumor resection between 2001 and 2013 at our institution. Competing risks methods were used to estimate the cumulative incidence of local failure. We also assessed possible predictive factors of local failure. RESULTS: Fifty-nine procedures (41 LDR and 18 HDR) were performed on 58 patients. Median follow-up was 55.1 months. Cumulative incidence of local failure at 1, 2, and 3 years was 28.5%, 34.2%, and 34.2%, respectively. Median overall survival was 39.9 months. There was no significant difference in local failure according to margin status, HDR vs. LDR, use of adjuvant external beam radiotherapy, or metastatic vs. primary tumor. Two patients (3.4%) experienced Grade 3+ toxicities likely related to brachytherapy. Additionally, 7 patients experienced Grade 3+ postsurgical complications unlikely related to brachytherapy. CONCLUSIONS: IORT is associated with good local control after resection of thoracic tumors otherwise at very high risk for local recurrence. There is a low incidence of severe toxicity attributable to brachytherapy. HDR-IORT appears to have equivalent outcomes to LDR-IORT. HDR or LDR-IORT can, therefore, be considered in situations where the oncologic completeness of thoracic tumor resection is in doubt. PMID- 26825858 TI - Focused Critical Care Echocardiography: Development and Evaluation of an Image Acquisition Assessment Tool. AB - OBJECTIVES: Little attention has been placed on assessment tools to evaluate image acquisition quality for focused critical care echocardiography. We designed a novel assessment tool to objectively evaluate the image acquisition skills of critical care trainees learning focused critical care echocardiography and examined the tool for evidence of validity. DESIGN: Prospective observational study. SETTING: Medical-surgical ICUs at a tertiary care teaching hospital. SUBJECTS: Trainees in our critical care medicine fellowship program. INTERVENTIONS: Six trainees completed a focused critical care echocardiography training curriculum followed by performing 20 transthoracic echocardiograms on patients receiving invasive mechanical ventilation. At three assessment intervals (the 1st and 2nd examinations, 10th and 11th examinations, and 19th and 20th examinations), echocardiograms performed by trainees were compared with those of critical care physicians certified in echocardiography and scored according to the focused critical care echocardiography assessment tool. The primary outcome was an efficiency score (overall assessment tool score divided by examination time). Differences in mean efficiency scores between echocardiographers of differing skill levels and changes in trainees' mean efficiency scores with increasing focused critical care echocardiography experience were compared by using t tests. MEASUREMENTS AND MAIN RESULTS: On the initial assessment, mean efficiency scores (SD) for trainees and experienced physicians were 1.55 (0.95) versus 2.78 (1.38), respectively (p = 0.02), and for the second and third assessments, the corresponding efficiency ratings for trainees and experienced physicians were 2.48 (0.97) versus 4.55 (1.32) (p < 0.01) and 2.61 (1.37) versus 4.17 (2.12) (p = 0.04), respectively. CONCLUSIONS: Trainees' efficiency in focused critical care echocardiography image acquisition improved quickly in the first 10 studies, yet, it could not match with the performance of experienced physicians after 20 focused critical care echocardiography studies. The focused critical care echocardiography assessment tool demonstrated evidence of validity and could discern changes in trainees' image acquisition performance with increasing experience. PMID- 26825859 TI - The Role of Extracellular Adenosine Triphosphate in Ischemic Organ Injury. AB - OBJECTIVES: Ischemic tissue injury contributes to significant morbidity and mortality and is implicated in a range of pathologic conditions, including but not limited to myocardial infarction, ischemic stroke, and acute kidney injury. The associated reperfusion phase is responsible for the activation of the innate and adaptive immune system, further accentuating inflammation. Adenosine triphosphate molecule has been implicated in various ischemic conditions, including stroke and myocardial infarction. STUDY SELECTION: Adenosine triphosphate is a well-defined intracellular energy transfer and is commonly referred to as the body's "energy currency." However, Laboratory studies have demonstrated that extracellular adenosine triphosphate has the ability to initiate inflammation and is therefore referred to as a damage-associated molecular pattern. Purinergic receptors-dependent signaling, proinflammatory cytokine release, increased Ca influx into cells, and subsequent apoptosis have been shown to form a common underlying extracellular adenosine triphosphate molecular mechanism in ischemic organ injury. CONCLUSIONS: In this review, we aim to discuss the molecular mechanisms behind adenosine triphosphate-mediated ischemic tissue injury and evaluate the role of extracellular adenosine triphosphate in ischemic injury in specific organs, in order to provide a greater understanding of the pathophysiology of this complex process. We also appraise potential future therapeutic strategies to limit damage in various organs, including the heart, brain, kidneys, and lungs. PMID- 26825860 TI - Instability of different adolescent metabolic syndrome definitions tracked into early adulthood metabolic syndrome: Tehran Lipid and Glucose Study (TLGS). AB - BACKGROUND AND OBJECTIVE: There are substantial controversies about the clinical utility of adolescent metabolic syndrome (MetS). The current study examined the stability of adolescent MetS by assessing the agreement and discriminative abilities of four different definitions of adolescent MetS and the adult MetS definition during a 10.4-yr follow up. SUBJECTS AND METHODS: For this study, 1424 adolescents (55.2% female), who participated in the framework of the Tehran Lipid and Glucose Study were included. Kappa was calculated for agreement between adolescent MetS definitions [Cook, de Ferranti, pediatric National Cholesterol Education Program (NCEP) and pediatric International Diabetes Federation (IDF)] and the adulthood MetS definition defined by the joint interim statement (JIS) criteria. MetS persistence, instability, and incidence were assessed, and for each of the four adolescent definitions, sensitivity, specificity, and area under receiver operating curve (AUC) for the counting of categorical adulthood MetS components was evaluated. RESULTS: The agreement between the four adolescent MetS definitions and JIS was poor (kappa = 0.094-0.255). All definitions showed low sensitivity and high specificity, except for de Ferranti's, which contrary to other definitions, had higher sensitivity and lower specificity. All four adolescent definitions revealed generally low AUCs (0.601-0.647). Compared with the pubertal group (11-14 yr), the predictive power was slightly higher in the late-pubertal group (15-18 yr). Cook's and de Ferranti's definitions showed fairly better predictive powers (0.647 and 0.644, respectively). Across all definitions, instability ranged between 5.4 and 19.6%. CONCLUSION: The adolescent definitions show considerable amount of instability defined as poor agreement and low discriminative abilities tracked into early adulthood. PMID- 26825861 TI - Clinical evaluation of model-based radiostereometric analysis to measure femoral head penetration and cup migration in four different cup designs. AB - In conventional Radiostereometric analysis (RSA) implants with attached tantalum markers are frequently used, which may be difficult to visualize. This problem can be avoided with model-based RSA (MBRSA), but it is uncertain if this method has the same precision as marker-based RSA. We evaluated the influence of cup design for the precision of MBRSA in four uncemented cups to study if the design had any influence on the precision. Stereo radiographs were analyzed postoperatively (double-examinations) and after 2 years (single examinations). The difference between the double-examinations was used to compute the precision for the methods and for each type of implant. Femoral head penetration and cup translation up to 2 years were compared using marker-based RSA as reference. The precision of proximal penetration and migration measurements did not differ between the methods for Trilogy, TMT and ABG. For Ringloc design a poorer precision was observed using MBRSA. Comparison between the methods regarding proximal penetration and cup migration at 2 years did not differ for three of the designs (p = 0.12-0.91). However, for the group with porous plasma sprayed surface (Ringloc) a significant difference between the methods was observed (ppenetration <0.01 and pmigration <0.01). Poorer precision, different penetration and migration values at 2 years for one of the designs indicate that the resolution of MBRSA might vary depending on surface coating and implant geometry. Therefore, we conclude that the resolution of MBRSA has to be studied for each type of basic cup design. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:760-767, 2017. PMID- 26825862 TI - Is Hearing Loss Associated with Poorer Health in Older Adults Who Might Benefit from Hearing Screening? AB - OBJECTIVES: Hearing screening programs may benefit adults with unacknowledged or unaddressed hearing loss, but there is limited evidence regarding whether such programs are effective at improving health outcomes. The objective was to determine if poorer audiometric hearing thresholds are associated with poorer cognition, social isolation, burden of physical or mental health, inactivity due to poor physical or mental health, depression, and overnight hospitalizations among older American adults with unacknowledged or unaddressed hearing loss. DESIGN: The authors performed a cross-sectional population-based analysis of older American adults with normal hearing or unacknowledged or unaddressed hearing loss. Data was obtained from the 1999 to 2010 cycles of the National Health and Nutrition Examination Survey. Participants with a pure-tone average (PTA in the better hearing ear of thresholds at 0.5, 1, 2, and 4 kHz) > 25 dB HL who self-reported their hearing ability to be "good" or "excellent" were categorized as having "unacknowledged" hearing loss. Those who had a PTA > 25 dB HL and who self-reported hearing problems but had never had a hearing test or worn a hearing aid were categorized as having "unaddressed" hearing loss. Multivariate regression was performed to account for confounding due to demographic and health variables. RESULTS: A 10 dB increase in PTA was associated with a 52% increased odds of social isolation among 60- to 69-year-olds in multivariate analyses (p = 0.001). The average Digit Symbol Substitution Test score dropped by 2.14 points per 10 dB increase in PTA (p = 0.03), a magnitude equivalent to the drop expected for 3.9 years of chronological aging. PTA was not associated significantly with falls, hospitalizations, burden of physical or mental health, or depression, or social isolation among those ages 70 years or older in these samples. CONCLUSION: Unacknowledged or unaddressed hearing loss was associated with a significantly increased risk of social isolation among 60- to 69-year-olds but not those 70 years or older. It was also associated with lower cognitive scores on the Digit Symbol Substitution Test among 60- to 69-year olds. This study differs from prior studies by focusing specifically on older adults who have unacknowledged or unaddressed hearing loss because they are the most likely to benefit from pure-tone hearing screening. The finding of associations between hearing loss and measures of social isolation and cognition in these specific samples extends previous findings on unrestricted samples of older adults including those who had already acknowledged hearing problems. Future randomized controlled trials measuring the effectiveness of adult hearing screening programs should measure whether interventions have an effect on these measures in those who have unacknowledged or unaddressed pure-tone hearing loss. PMID- 26825863 TI - Oxidative stress and rheologic properties of stored red blood cells before and after transfusion to surgical patients. AB - BACKGROUND: The loss of structural and functional integrity of red blood cells (RBCs) during storage, collectively referred to as "storage lesion," has been implicated in reduced oxygen delivery after transfusion. RBCs are highly susceptible to oxidative damage from generation of reactive oxygen species by autoxidation of hemoglobin. Therefore, we examined whether increased oxidative stress (OS) in stored RBCs is associated with impaired cell membrane deformability before or after transfusion. STUDY DESIGN AND METHODS: Thirty-four patients undergoing multilevel spine fusion surgery were enrolled. OS in RBCs was assessed by the presence of fluorescent heme degradation products and methemoglobin, which were measured with fluorimetric and spectrophotometric methods, respectively. Deformability and aggregation were determined by ektacytometry in stored RBCs, autologous salvaged RBCs, and posttransfusion blood samples. RESULTS: OS in stored RBCs was significantly increased with longer storage (R = 0.54, p = 0.032) and significantly higher than that in fresh RBCs (9.1 +/- 1.3 fluorescent arbitrary units vs. 7.7 +/- 0.9 fluorescent arbitrary units, p < 0.001). Deformability decreased (R = -0.60, p = 0.009) with increasing storage duration. OS was elevated (p < 0.05) and deformability was decreased (p < 0.05) in postoperative blood from patients who had undergone moderate (>=4 RBC units) but not minimal or no transfusion. Neither the decrease in deformability of RBCs nor the aggregation changes were correlated with OS. CONCLUSIONS: Although stored RBCs show signs of increased OS and loss of cell membrane deformability, these changes were not directly correlated and were only evident after moderate but not lower dose transfusion in postoperative surgical patients. These findings suggest that factors other than OS may contribute to impaired rheology with stored RBCs in the clinical setting. PMID- 26825864 TI - Endoscopic Ultrasound Elastography: Current Clinical Use in Pancreas. AB - Elastography is a newer technique for the assessment of tissue elasticity using ultrasound. Cancerous tissue is known to be stiffer (hence, less elastic) than corresponding healthy tissue, and as a result, could be identified in an elasticity-based imaging. Ultrasound elastography has been used in the breast, thyroid, and cervix to differentiate malignant from benign neoplasms and to guide or avoid unnecessary biopsies. In the liver, elastography has enabled a noninvasive and reliable estimate of fibrosis. Endoscopic ultrasound has become a robust diagnostic and therapeutic tool for the management of pancreatic diseases. The addition of elastography to endoscopic ultrasound enabled further characterization of pancreas lesions, and several European and Asian studies have reported encouraging results. The current clinical role of endoscopic ultrasound elastography in the management of pancreas disorders and related literature are reviewed. PMID- 26825865 TI - Profiling of cMET and HER Family Receptor Expression in Pancreatic Ductal Adenocarcinomas and Corresponding Lymph Node Metastasis to Assess Relevant Pathways for Targeted Therapies: Looking at the Soil Before Planting the Seed. AB - OBJECTIVES: Comprehensive assessment of cMET and HER family receptor tyrosine kinases expression, changes of expression during metastatic progression, amplification status of the MET gene, and correlations with patient characteristics in pancreatic ductal adenocarcinoma (PDAC) was conducted. METHODS: We investigated 56 PDACs and corresponding lymph node metastases for HER1 to HER4 and cMET expression by immunohistochemistry, as well as cMET gene copy numbers by chromogenic in situ hybridization. RESULTS: Of all receptor tyrosine kinases evaluated, cMET expression was highest with 46.5% of tumors showing moderate or strong expression and a weak correlation with gene copy number status (P = 0.04; Spearman rho = 0.28). cMET expression was increased in metastases. In contrast, expression levels of HER family receptors were generally low both in primaries and metastases. A weak yet significant correlation of HER1 and cMET expression levels was observed (P < 0.001; Spearman rho = 0.44) and HER1 was often present in poorly differentiated tumors (G3, P = 0.049). CONCLUSIONS: Our data suggest that cMET might constitute an interesting molecule for combining targeted and chemotherapeutic approaches in PDAC, because expression is frequent and increased during metastatic progression. In PDAC, cMET protein expression might be a more useful stratification biomarker than cMET gene amplification, which does not seem to be its primary regulator. PMID- 26825866 TI - Campylorrhinus lateralis, Bilateral microphthalmia and odontoma temporalis in an Oldenburg Foal. AB - An Oldenburg colt with wry nose was autopsied after having lived for only 30 min. It presented cyanotic oral mucosae, underdeveloped eyes and a right-sided temporal osseous mass. The applicable nomenclature for the defects is discussed, and the potential etiopathogenesis is explored by describing the normal embryonic development of the affected body parts. PMID- 26825867 TI - Population pharmacokinetic/pharmacodynamic modeling of tumor growth kinetics in medullary thyroid cancer patients receiving cabozantinib. AB - Nonlinear mixed effects models were developed to describe the relationship between cabozantinib exposure and target lesion tumor size in a phase III study of patients with progressive metastatic medullary thyroid cancer. These models used cabozantinib exposure estimates from a previously published population pharmacokinetic model for cabozantinib in cancer patients that was updated with data from healthy-volunteer studies. Semi-mechanistic models predict well for tumors with static, increasing, or decreasing growth over time, but they were not considered adequate for predicting tumor sizes in medullary thyroid cancer patients, among whom an early reduction in tumor size was followed by a late stabilization phase in those receiving cabozantinib. A semi-empirical tumor model adequately predicted tumor profiles that were assumed to have a net growth rate constant that was piecewise continuous in the regions of 0-110 and 110-280 days. Emax models relating average concentration to average change in tumor size predicted that an average concentration of 79 and 58 ng/ml, respectively, would yield 50% of the maximum possible tumor reduction during the first 110 days of dosing and during the subsequent 110-280 days of dosing. Simulations of tumor responses showed that daily doses of 60 mg or greater are expected to provide a similar tumor reduction. Both model evaluation of observed data and simulation results suggested that the two protocol-defined cabozantinib dose reductions from 140 to 100 mg/day and from 100 to 60 mg/day are not projected to result in a marked reduction in target lesion regrowth. PMID- 26825868 TI - Trastuzumab use during pregnancy: long-term survival after locally advanced breast cancer and long-term infant follow-up. AB - Here, we describe the case of a patient diagnosed with locally advanced breast cancer 8 years ago. Her treatment course was neoadjuvant chemotherapy, followed by mastectomy and then adjuvant radiotherapy and trastuzumab (TTZ). During the use of adjuvant targeted therapy, an incidental pregnancy was diagnosed. Four years later, she developed bone and cerebral metastases, and since then, she has received courses of TTZ, capecitabine, lapatinib, and radiotherapy with intermittent control of the disease. Her 7-year-old son presents a normal physical and long-term neurological developmental curve according to specialized evaluation. This case is unique for several reasons: the patient received the highest dose of TTZ yet described during pregnancy (4400 mg); there has been a long period of disease-free survival after treatment for locally advanced breast cancer and long overall survival despite successive disease progressions during the metastatic phase of the disease (97 months), and there was a monitored pediatric follow-up period (7 years). PMID- 26825869 TI - Reduced folate and serum vitamin metabolites in patients with rectal carcinoma: an open-label feasibility study of pemetrexed with folic acid and vitamin B12 supplementation. AB - The objectives of this single-center, open-label, phase II study were to evaluate (a) the feasibility and safety of neoadjuvant administration of pemetrexed with oral folic acid and vitamin B12 (FA/B12) in newly diagnosed patients with resectable rectal cancer and (b) intracellular and systemic vitamin metabolism. Patients were treated with three cycles of pemetrexed (500 mg/m, every 3 weeks) and FA/B12 before surgery. The reduced folates tetrahydrofolate, 5 methyltetrahydrofolate, and 5,10-methylenetetrahydrofolate were evaluated from biopsies in tumor tissue and in adjacent mucosa. Serum levels of homocysteine, cystathionine, and methylmalonic acid were also measured. All 37 patients received three cycles of pemetrexed; 89.2% completed their planned dosage within a 9-week feasibility time frame. Neither dose reductions nor study drug-related serious adverse events were reported. Reduced folate levels were significantly higher in tumor tissue compared with adjacent mucosa at baseline. After FA/B12 administration, tissue levels of reduced folates increased significantly and remained high during treatment in both tumor and mucosa until surgery. Serum levels of cystathionine increased significantly compared with baseline after FA/B12 administration, but then decreased, fluctuating cyclically during pemetrexed therapy. Homocysteine and methylmalonic acid levels decreased significantly after FA/B12 administration, and remained below baseline levels during the study. These results indicate that administration of three neoadjuvant cycles of single-agent pemetrexed, every 3 weeks, with FA/B12 in patients with resectable rectal cancer is feasible and tolerable. Tissue and serum vitamin metabolism results demonstrate the influence of pemetrexed and FA/B12 on vitamin metabolism and warrant further study. PMID- 26825870 TI - The Effectiveness of Early Educational Interventions in the Emergency Department to Reduce Incidence or Severity of Postconcussion Syndrome Following a Concussion: A Systematic Review. AB - OBJECTIVES: Concussions or mild traumatic brain injury are a major public health concern accounting for 85% of all brain injuries. Postconcussion syndrome (PCS) has been found to affect between 15 and 25% of patients with concussion 1 year after the initial injury. The goal of this review is to assess the effectiveness of early educational information or interventions provided in the emergency department on the onset and/or severity of PCS. METHODS: A comprehensive literature search strategy involving seven electronic databases was developed. A grey literature search of Google Scholar, recent conference proceedings in emergency medicine, bibliographies of included studies, and clinical trial registries was also performed. The citation list was reviewed independently by two reviewers; no restrictions on publication status or language of publication were applied. The Cochrane risk-of-bias tool and the Newcastle-Ottawa scale were used to assess quality. RESULTS: From 1,325 citations retrieved, four RCTs and one controlled clinical trial met inclusion criteria. Interventions identified in these studies included: educational information sheets, with or without telephone or in-person follow-up, and one study on bed rest. While rarely requested, one study offered referrals and additional treatment, if needed. None of the studies were deemed to be high quality. Heterogeneity among outcome reporting, follow-up dates and interventions used precluded a pooled analysis. Overall, only two of the five included studies involving adult patients receiving early educational interventions reported a significant improvement in PCS symptoms. No reduction in PCS symptoms was found in the study on bed rest interventions. CONCLUSION: Limited evidence exists regarding the effectiveness of early educational interventions following concussion. Standardization of the interventions, outcome measures, and follow-up periods would make quantitative comparisons more valid. Moreover, higher-quality research in the field of early interventions for patients in the acute care setting is urgently required. PMID- 26825871 TI - Activation of mTORC1 in B Lymphocytes Promotes Osteoclast Formation via Regulation of beta-Catenin and RANKL/OPG. AB - The cytokine receptor activator of nuclear factor-kappaB ligand (RANKL) induces osteoclast formation from monocyte/macrophage lineage cells. However, the mechanisms by which RANKL expression is controlled in cells that support osteoclast differentiation are still unclear. We show that deletion of TSC1 (tuberous sclerosis complex 1) in murine B cells causes constitutive activation of mechanistic target of rapamycin complex 1 (mTORC1) and stimulates RANKL but represses osteoprotegerin (OPG) expression and subsequently promotes osteoclast formation and causes osteoporosis in mice. Furthermore, the regulation of RANKL/OPG and stimulation of osteoclastogenesis by mTORC1 was confirmed in a variety of RANKL-expressing cells and in vivo. Mechanistically, mTORC1 controls RANKL/OPG expression through negative feedback inactivation of Akt, destabilization of beta-catenin mRNA, and downregulation of beta-catenin. Our findings demonstrate that mTORC1 activation-stimulated RANKL expression in B cells is sufficient to induce bone loss and osteoporosis. The study also established a link between mTORC1 and the RANKL/OPG axis via negative regulation of beta-catenin. (c) 2016 American Society for Bone and Mineral Research. PMID- 26825872 TI - Distinctive role of KV1.1 subunit in the biology and functions of low threshold K(+) channels with implications for neurological disease. AB - The diversity of pore-forming subunits of KV1 channels (KV1.1-KV1.8) affords their physiological versatility and predicts a range of functional impairments resulting from genetic aberrations. Curiously, identified so far human neurological conditions associated with dysfunctions of KV1 channels have been linked exclusively to mutations in the KCNA1 gene encoding for the KV1.1 subunit. The absence of phenotypes related to irregularities in other subunits, including the prevalent KV1.2 subunit of neurons is highly perplexing given that deletion of the corresponding kcna2 gene in mouse models precipitates symptoms reminiscent to those of KV1.1 knockouts. Herein, we critically evaluate the molecular and biophysical characteristics of the KV1.1 protein in comparison with others and discuss their role in the greater penetrance of KCNA1 mutations in humans leading to the neurological signs of episodic ataxia type 1 (EA1). Future research and interpretation of emerging data should afford new insights towards a better understanding of the role of KV1.1 in integrative mechanisms of neurons and synaptic functions under normal and disease conditions. PMID- 26825873 TI - Establishment of a renal supportive care program: Experience from a rural community hospital in Taiwan. AB - Renal supportive care (RSC) denotes a care program dedicated for patients with acute, chronic renal failure, and end-stage renal disease (ESRD), aiming to offer maximal symptom relief and optimize patients' quality of life. The uncertainty of prognosis for patients with chronic kidney disease and ESRD, the sociocultural issues inherent to the Taiwanese society, and the void of structured and practical RSC pathway, contributes to the underrecognition and poor utilization of RSC. Taiwanese patients rarely receive information regarding RSC as part of a standardized care and are not commonly offered this option. In National Taiwan University Hospital Jinshan branch, we started a RSC subprogram, supported by the community-based palliative/hospice care main program. We focused on understanding the need and providing the choice of RSC to suitable candidates. A three-step and four-phase protocol was designed and implemented to identify appropriate patients and to enhance the applicability of the RSC. We harnessed family visit and home based family meeting as a vehicle to understand the patients' preferences, to discover what ESRD patients and their family value most, and to introduce the option of RSC. In the current review, we described our pilot experience of establishing a RSC program in Taiwan, and discuss its potential advantage. PMID- 26825874 TI - Transforming growth factor type beta (TGF-beta) requires reactive oxygen species to induce skeletal muscle atrophy. AB - Transforming growth factor beta 1 (TGF-beta1) is a classical modulator of skeletal muscle and regulates several processes, such as myogenesis, regeneration, and muscle function in skeletal muscle diseases. Skeletal muscle atrophy, characterised by the loss of muscle strength and mass, is one of the pathological conditions regulated by TGF-beta. Atrophy also results in increased myosin heavy chain (MHC) degradation and the expression of two muscle-specific E3 ubiquitin ligases, atrogin-1 and MuRF-1. Reactive oxygen species (ROS) are modulators of muscle wasting, and NAD(P)H oxidase (NOX) is one of the main sources of ROS. While it was recently found that TGF-beta1 induces atrophy in skeletal muscle, the underlying mechanism is not fully understood. In this study, the role of NOX-derived ROS in skeletal muscle atrophy induced by TGF-beta was assessed. TGF-beta1 induced an atrophic effect in C2C12 myotubes, as evidenced by decreased myotube diameter and MHC levels, together with increased MuRF-1 levels. Concomitantly, TGF-beta increased NOX-induced ROS contents. Interestingly, NOX inhibition through apocynin and the antioxidant treatment with N-acetyl cysteine (NAC) decreased increased ROS levels in myotubes. Additionally, both apocynin and NAC completely prevented the decreased MHC, decreased myotube diameter, and increased MuRF-1 induced by TGF-beta. Injection of TGF-beta1 into the tibialis anterior muscle induced atrophy, as observed by decreased fibre diameter and MHC levels, together with increased MuRF-1 levels. Likewise, TGF-beta increased the ROS contents in the smaller fibres of skeletal muscle. Additionally, the administration of NAC to mice prevented all atrophic effects and the increase in ROS induced by TGF-beta in the tibialis anterior. This is the first study to report that TGF-beta has an atrophic effect dependent on NOX-induced ROS in skeletal muscle. PMID- 26825875 TI - Involvement of homocysteine, homocysteine thiolactone, and paraoxonase type 1 (PON-1) in the etiology of defective human sperm function. AB - This study reports, for the first time, the significant (p <= 0.01) accumulation of homocysteine residues in low density, defective sperm suspensions isolated from patients attending an infertility clinic. This overabundance of homocysteine was not related to a deficiency in folate availability but may have been a reflection of the oxidative stress that characterizes such defective sperm populations. Direct addition of the homocysteine cyclic congener, homocysteine thiolactone, to human spermatozoa resulted in the rapid induction of mitochondrial reactive oxygen species (ROS) generation (p < 0.001), the stimulation of lipid peroxidation (p < 0.01), the promotion of tyrosine phosphorylation (p < 0.001), and the suppression of sperm motility (p < 0.001) in the absence of any significant impact on DNA integrity. The parent homocysteine molecule was less active and took 24 h to stimulate mitochondrial ROS production possibly because of the need to convert this compound to the corresponding thiolactone before it could exert a measureable biological effect. Thiolactone was also effective in suppressing the carboxymethylation of key proteins in the sperm tail, which are thought to be involved in the regulation of sperm movement. The major enzyme responsible for removing thiolactone from proteins, paraoxonase (PON-1), was shown to be a major target for alkylation by lipid aldehydes, such as 4-hydroxynonenal, generated as a consequence of oxidative stress. Exposure of human spermatozoa to such aldehydes resulted in a dose-dependent accumulation of homocysteine in spermatozoa (p < 0.03). These results suggest that one of the consequences of oxidative stress in mammalian spermatozoa is the inhibition of PON-1, which then enhances the availability of homocysteine thiolactone to interact with the epsilon-amino group of lysine residues on sperm proteins, triggering a raft of significant biological changes in these cells that ultimately compromise sperm function. PMID- 26825876 TI - Clinical Features, Short-Term Mortality, and Prognostic Risk Factors of Septic Patients Admitted to Internal Medicine Units: Results of an Italian Multicenter Prospective Study. AB - Only a few studies provided data on the clinical history of sepsis within internal Medicine units. The aim of the study was to assess the short-term mortality and to evaluate the prognostic risk factors in a large cohort of septic patients treated in internal medicine units. Thirty-one internal medicine units participated to the study. Within each participating unit, all admitted patients were screened for the presence of sepsis. A total of 533 patients were included; 78 patients (14.6%, 95%CI 11.9, 18.0%) died during hospitalization; mortality rate was 5.5% (95% CI 3.1, 9.6%) in patients with nonsevere sepsis and 20.1% (95%CI 16.2, 28.8%) in patients with severe sepsis or septic shock. Severe sepsis or septic shock (OR 4.41, 95%CI 1.93, 10.05), immune system weakening (OR 2.10, 95%CI 1.12, 3.94), active solid cancer (OR 2.14, 95% CI 1.16, 3.94), and age (OR 1.03 per year, 95% CI 1.01, 1.06) were significantly associated with an increased mortality risk, whereas blood culture positive for Escherichia coli was significantly associated with a reduced mortality risk (OR 0.46, 95%CI 0.24, 0.88). In-hospital mortality of septic patients treated in internal medicine units appeared similar to the mortality rate obtained in recent studies conducted in the ICU setting. PMID- 26825877 TI - Application of Ultrasound-Guided Core Biopsy to Minimal-Invasively Diagnose Supraclavicular Fossa Tumors and Minimize the Requirement of Invasive Diagnostic Surgery. AB - Tumors of the supraclavicular fossa (SC) is clinically challenging because of anatomical complexity and tumor pathological diversity. Because of varied diseases entities and treatment choices of SC tumors, making the accurate decision among numerous differential diagnoses is imperative. Sampling by open biopsy (OB) remains the standard procedure for pathological confirmation. However, complicated anatomical structures of SC always render surgical intervention difficult to perform. Ultrasound-guided core biopsy (USCB) is a minimally invasive and office-based procedure for tissue sampling widely applied in many diseases of head and neck. This study aims to evaluate the clinical efficacy and utility of using USCB as the sampling method of SC tumors. From 2009 to 2014, consecutive patients who presented clinical symptoms and signs of supraclavicular tumors and were scheduled to receive sampling procedures for diagnostic confirmation were recruited. The patients received USCB or OB respectively in the initial tissue sampling. The accurate diagnostic rate based on pathological results was 90.2% for USCB, and 93.6% for OB. No significant difference was noted between USCB and OB groups in terms of diagnostic accuracy and the percentage of inadequate specimens. All cases in the USCB group had the sampling procedure completed within 10 minutes, but not in the OB group. No scars larger than 1 cm were found in USCB. Only patients in the OB groups had the need to receive general anesthesia and hospitalization and had scars postoperatively. Accordingly, USCB can serve as the first-line sampling tool for SC tumors with high diagnostic accuracy, minimal invasiveness, and low medical cost. PMID- 26825878 TI - Comparative Evaluation of Liposomal Albendazole and Tablet-Albendazole Against Hepatic Cystic Echinococcosis: A Non-Randomized Clinical Trial. AB - In this study, we aimed to compare the clinical efficacy of liposomal albendazole (L-ABZ) and tablet-albendazole (T-ABZ) for the treatment of human hepatic cystic echinococcosis (CE). Sixty patients with single cyst (CE1) or daughter cyst (CE2) were included in this study and were nonrandomly divided into the L-ABZ group (n = 30, 10 mg/kg per day, p.o., b.i.d.) and T-ABZ group (n = 30, 12-20 mg/kg per day, p.o., b.i.d.), respectively. The treatment duration lasted for 6 months, during which dynamic follow-up was carried out to evaluate the clinical efficacy through calculating the total effective rates (TERs). Measurement data and numerous data were analyzed by the chi-square test. Two-sided tests were performed for all the statistical tests. In our study, 2 patients were lost in the follow-up in the L-ABZ group. One patient was lost in the follow-up in the T ABZ group, and 1 patient was withdrawal from the study due to receiving surgery. Significant difference was identified in the 3-month TERs of L-ABZ group and T ABZ group (33.3% vs 76.7%, P < 0.05). Also, remarkable difference was noted in the 6-month TERs in the L-ABZ group and T-ABZ group (66.7% vs 93.3%, P = 0.01). No statistical difference was noticed in the incidence rate of adverse reactions in both groups (P > 0.05). Based on our study, both T-ABZ and L-ABZ are effective for treating human CE. The TER in the L-ABZ group is superior to that of T-ABZ. PMID- 26825879 TI - GNA11 Mutation in a Patient With Cutaneous Origin Melanoma: A Case Report. AB - The rapid advances in the molecular biology and genetics have improved the understanding of molecular pathogenesis of v-Raf murine sarcoma viral oncogene homolog B (BRAF), feline sarcoma viral oncogene v-kit (KIT), and neuroblastoma v Ras oncogene homolog (NRAS) mutant melanomas with the subsequent development of targeted therapeutic agents. However, only limited data are available for melanoma harboring other somatic than BRAF, KIT, and NRAS mutations. Mutations in guanine nucleotide-binding protein Q polypeptide (GNAQ) and guanine nucleotide binding protein alpha-11 (GNA11), alpha subunits of heterotrimeric G proteins, constitutively activate mitogen-activated protein kinase (MAPK) pathway in uveal melanoma. However, there are no reports of GNA11 mutations in cutaneous melanomas. A 48-year-old woman was diagnosed with cutaneous nodular melanoma on the left scalp. Mutation analysis of the tumor revealed a GNA11 Q209L mutation. There was no evidence of uveal melanoma or malignant blue nevus in ophthalmologic exam, imaging studies, and pathology review. To our knowledge, this is the first case report to demonstrate cutaneous origin melanoma harboring a GNA11 Q209L mutation. PMID- 26825880 TI - Latent Tuberculosis Infection and the Risk of Subsequent Cancer. AB - The association of latent tuberculosis infection (LTBI) with subsequent cancer remains unclear. We investigated the risk of future cancer among tuberculosis (TB) contacts with or without subsequent TB activation. Using the Taiwan National Health Insurance Research Database, we conducted a nationwide population-based study. TB contacts during 1997 to 2012 were included as the study cohort. Patients with antecedent cancer and TB were excluded. Data from 11,522 TB contacts and 46,088 age-, sex-, and enrollment date-matched subjects during 1997 to 2012 were analyzed. The 2 cohorts were monitored until December 31, 2012 for incidence of cancer and TB infection. LTBI was defined as a TB contact with subsequent TB activation. The primary endpoint was occurrence of newly diagnosed cancer. There was no difference in cancer development between the TB contact cohort and comparison cohort (log-rank test, P = 0.714). After multivariate adjustment, the hazard ratio (HR) for cancer among the LTBI patients was 2.29 [95% confidence interval (CI), 1.26-4.17; P = 0.007]. There was increase in cancer incidences for several specific cancer types, including multiple myeloma (HR 340.28), lung (HR 2.69), kidney and bladder (HR 6.16), hepatobiliary (HR 2.36), and gastrointestinal (HR 2.99) cancers. None of the 136 TB contacts who received isoniazid prophylaxis developed cancer. LTBI patients had a higher risk of future cancer. PMID- 26825881 TI - Excessive Sleep and Lack of Sleep Are Associated With Slips and Falls in the Adult Korean Population: A Population-Based Cross-Sectional Study. AB - Few studies have evaluated the impacts of excessive sleep duration on falls. This study investigated the associations between sleep duration and falls among Korean adults in a wide range of age groups while adjusting for numerous confounding factors. Data collected from study participants ranging in age from 19 to 109 years old were analyzed from the 2013 Korean Community Health Survey (KCHS). Sleep duration was divided into 5 groups: <=5, 6, 7, 8, and >=9 hours per day. The relations between sleep duration and falls (>=1 time or >=2 times per year) were analyzed using simple and multiple logistic regression analyses with complex sampling. Age, sex, days of vigorous or moderate physical activity, income, education, alcohol use, smoking, stress, obesity, hypertension, diabetes mellitus, hyperlipidemia, stroke, angina or myocardial infarction, arthritis, and asthma were controlled for as confounding factors. Associations between sleep duration and falls were analyzed in 19 to 40, 41 to 60, and 61+ year age groups. Furthermore, the relations between sleep duration and indoor versus outdoor falls were analyzed. Both <=6 and >=8 hours of sleep per day were significantly associated with an increased incidence of falls (>=1 time and >=2 times per year) in the overall adult population (P < 0.001 in both instances). In a subgroup analysis, sleep durations of <=5 and >=9 hours were significantly associated with an increased incidence of falls (>=1 time a year) in each age group. Six hours of sleep was not significantly associated with falls (>=2 times per year) in the 61+ year age group, and 8 and 9 hours of sleep were not significantly associated with falls (>=2 times a year) in the 19 to 40 year age group. This study demonstrated that long as well as short sleep durations are associated with an increased incidence of falls. However, these relations were not evident in elderly populations with short sleep durations or in young adults with long sleep durations. PMID- 26825882 TI - Significantly Higher Peripheral Insulin-Like Growth Factor-1 Levels in Patients With Major Depressive Disorder or Bipolar Disorder Than in Healthy Controls: A Meta-Analysis and Review Under Guideline of PRISMA. AB - An increasing amount of research has focused on insulin-like growth factor-1 (IGF 1) because of multiple neurotrophic effects, including neurogenesis, remyelination, and synaptogenesis. In addition, IGF-1 can mediate an antidepressant effect in patients with major affective disorder, and its levels in the cerebrospinal fluid have been found to vary with antidepressant treatment. Furthermore, it has been proven to crossover the blood-brain barrier, with a reciprocal feedback loop being the central effect. However, recent studies have reported inconclusive findings about the role of IGF-1 in major affective disorder. The aim of the current study was to conduct a thorough meta-analysis of changes in peripheral IGF-1 levels in patients with major depressive disorder (MDD) or bipolar disorder (BD). We conducted a thorough literature search and compared peripheral IGF-1 levels in patients with MDD or BD and in healthy controls, and investigated clinical variables through meta-regression. Electronic research was conducted through platform of PubMed. We used inclusion criteria as clinical trials discussing comparisons of peripheral IGF-1 protein levels in patients with MDD or BD and those in healthy controls. We analyzed the cases from 9 studies with the random-effect model. The main finding was that peripheral IGF 1 levels in the patients were significantly higher than in the healthy controls (P < 0.001), with a significant inverse association with duration of illness (P = 0.03). In meta-analysis comparing peripheral IGF-1 levels in patients with BD or MDD before and after treatment, there was no significant change in peripheral IGF 1 levels after treatment (P = 0.092). The small numbers of studies and lack of correlation data with growth hormone in current studies are the main limitations of this meta-analysis. Our results indicated that peripheral IGF-1 levels may not be an indicator of disease severity, but may be a disease trait marker or an indicator of cognition. However, further investigations on the correlation between cognitive function and peripheral IGF-1 levels are needed to explore the role of IGF-1 in the pathophysiology of MDD and BD. PMID- 26825883 TI - Role of the Intravoxel Incoherent Motion Diffusion Weighted Imaging in the Pre treatment Prediction and Early Response Monitoring to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer. AB - The aim of this study was to explore whether intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) can probe pre-treatment differences or monitor early response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC). Thirty-six patients with locally advanced breast cancer were imaged using multiple-b DWI with 12 b values ranging from 0 to 1000 s/mm(2) at the baseline, and 28 patients were repeatedly scanned after the second cycle of NAC. Subjects were divided into pathologic complete response (pCR) and nonpathologic complete response (non-pCR) groups according to the surgical pathologic specimen. Parameters (D, D*, f, maximum diameter [MD] and volume [V]) before and after 2 cycles of NAC and their corresponding change (Deltaparameter) between pCR and non-pCR groups were compared using the Student t test or nonparametric test. The diagnostic performance of different parameters was judged by the receiver-operating characteristic curve analysis. Before NAC, the f value of pCR group was significantly higher than that of non-pCR (32.40% vs 24.40%, P = 0.048). At the end of the second cycle of NAC, the D value was significantly higher and the f value was significantly lower in pCR than that in non-pCR (P = 0.001; P = 0.015, respectively), whereas the D* value and V of the pCR group was slightly lower than that of the non-pCR group (P = 0.507; P = 0.676, respectively). DeltaD was higher in pCR (-0.45 * 10(-3) mm(2)/s) than that in non-pCR (-0.07 * 10(-3) mm(2)/s) after 2 cycles of NAC (P < 0.001). Deltaf value in the pCR group was significantly higher than that in the non-pCR group (17.30% vs 5.30%, P = 0.001). There was no significant difference in DeltaD* between the pCR and non-pCR group (P = 0.456). The prediction performance of DeltaD value was the highest (AUC [area under the curve] = 0.924, 95% CI [95% confidence interval] = 0.759-0.990). When the optimal cut-off was set at -0.163 * 10(-3) mm(2)/s, the values for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were up to 100% (95% CI = 66.4-100), 73.7% (95% CI = 48.8-90.9), 64.3% (95% CI = 35.6-86.0), and 100% (95% CI = 73.2-99.3), respectively. IVIM-derived parameters, especially the D and f value, showed potential value in the pre-treatment prediction and early response monitoring to NAC in locally advanced breast cancer. DeltaD value had the best prediction performance for pathologic response after NAC. PMID- 26825884 TI - Invasive Bacterial Infection in Patients with Interleukin-1 Receptor-associated Kinase 4 Deficiency: Case Report. AB - Interleukin-1 receptor-associated kinase 4 (IRAK4) deficiency (OMIM #607676) is a rare primary immunodeficiency of innate immune defect. We identified 10 patients from 6 families with IRAK4 deficiency in Japan, and analyzed the clinical characteristics of this disease. Nine patients had homozygous c.123_124insA mutation, and 1 patient had c.123_124insA and another nonsense mutation (547C>T). Umbilical cord separation occurred on the 14th day after birth or thereafter. Two patients had no severe infections owing to the prophylactic antibiotic treatment. Severe invasive bacterial infections occurred before the age of 3 in the other 8 patients. Among them, 7 patients had pneumococcal meningitis. Five patients died of invasive bacterial infection during infancy, although intravenous antibiotic treatment was started within 24 hours after onset in 4 patients among them. Analysis of cerebrospinal fluid of the patients who had fatal meningitis revealed very low glucose levels with only mild pleocytosis. The clinical courses of invasive bacterial infections were often rapidly progressive despite the early, appropriate antibiotic treatment in IRAK4 deficiency patients. The early diagnosis and appropriate prophylaxis of invasive bacterial infections are necessary for the patients. PMID- 26825885 TI - Peritoneal Dialysis is Associated With A Better Survival in Cirrhotic Patients With Chronic Kidney Disease. AB - Peritoneal dialysis (PD) can be an ideal treatment in cirrhotic patients with ascites and chronic kidney disease stage 5 (CKD 5D) who require dialysis. The survival of cirrhotic patients with CKD 5D on PD, however, is not clear. We compared the survival of cirrhotic patients with CKD 5D on PD and the survival of those on HD. Two datasets including a cohort study of China Medical University Hospital (CMUH) from 2004 to 2013 and the Longitudinal National Health Insurance Database for Catastrophic Illness Patients (LHID-CIP) of Taiwan from 1996 to 2011 were analyzed. The survival of cirrhotic patients on PD and the propensity score matched cirrhotic patients on HD were analyzed using Cox proportional hazards regression. In CMUH cohort of 85 PD and 340 HD patients, the all-cause mortality was lower in PD patients compared to it in HD patients (hazard ratio [HR]: 0.48, 95% confidence interval [CI]: 0.31-0.74, P < 0.01) after adjustments for confounders. The severity of liver cirrhosis defined by Child-Turcotte-Pugh (CTP) class (P < 0.01) was independently associated with all-cause mortality. The model for end-stage liver disease (MELD) score, however, was not associated with all cause mortality. In the LHID-CIP cohort of 285 PD and 1140 HD patients, the HR of all-cause mortality in PD patients was 0.61 (95% CI: 0.47 - 0.79, P < 0.01), as compared with HD patients. PD in cirrhotic patients who need dialysis is associated with lower all-cause mortality than HD is. This association is independent of patients' comorbidity, severity of liver cirrhosis, and serum albumin levels. PMID- 26825886 TI - Significant Effect of Valproate Augmentation Therapy in Patients With Schizophrenia: A Meta-analysis Study. AB - Valproate is an anticonvulsant, which is also widely used for treating psychiatric disorders. Some clinical trials have demonstrated benefits of valproate augmentation therapy in schizophrenia. Previous meta-analysis showed inconsistent findings because of limited literature at that time. The aim of this study is to update the newer published data by conducting a meta-analysis of clinical efficacy of valproate augmentation therapy in patients with schizophrenia or schizoaffective disorder. Data sources include electronic research through platform of PubMed. Study eligibility criteria, participants, and interventions were as follows: the inclusion criteria included articles discussing comparisons of the treatment effect in schizophrenic patients treated with antipsychotic augmented with valproate and antipsychotics with/without placebo; articles on clinical trials in humans. The exclusion criteria were case reports or series and nonclinical trials. We compared the effect between antipsychotic treatment with valproate augmentation and antipsychotic monotherapy. Data from clinical trials were pooled by random-effects model, and possible confounding variables were examined through meta-regression and subgroup analysis. Data from 11 articles including 889 patients were included into current meta-analysis. We found patients treated with antipsychotics with valproate augmentation showed significantly more improvement in total psychopathology than those treated with antipsychotics only (P = 0.02). Results from open trials, but not from randomized controlled trials (P = 0.20), showed significant improvement (P = 0.01). In addition, the significance only persisted in the studies conducted with a shorter treatment duration (P < 0.001) rather than longer treatment duration (P = 0.23). There is no difference in the dropout rate between valproate augmentation and antipsychotic treatment only (P = 0.14). We could not perform a detailed meta-analysis for every category of antipsychotics, long-term effect, and safety profiles of valproate augmentation therapy in maintenance treatment, safety in pregnant patients, and subtype of schizophrenia. Our meta-analysis highlights the significantly better treatment effect with valproate augmentation therapy in patients with schizophrenia or schizoaffective disorder, and provides important evidence for supporting the practice of valproate augmentation therapy in these patients. PMID- 26825887 TI - Neurodevelopment in Early Childhood Affected by Prenatal Lead Exposure and Iron Intake. AB - No safe threshold level of lead exposure in children has been recognized. Also, the information on shielding effect of maternal dietary iron intake during pregnancy on the adverse effects of prenatal lead exposure on children's postnatal neurocognitive development is very limited. We examined the association of prenatal lead exposure and neurodevelopment in children at 6, 12, 24, and 36 months and the protective action of maternal dietary iron intake against the impact of lead exposure. The study participants comprise 965 pregnant women and their subsequent offspring of the total participants enrolled in the Mothers and Children's environmental health study: a prospective birth cohort study. Generalized linear model and linear mixed model analysis were performed to analyze the effect of prenatal lead exposure and mother's dietary iron intake on children's cognitive development at 6, 12, 24, and 36 months. Maternal late pregnancy lead was marginally associated with deficits in mental development index (MDI) of children at 6 months. Mothers having less than 75th percentile of dietary iron intake during pregnancy showed significant increase in the harmful effect of late pregnancy lead exposure on MDI at 6 months. Linear mixed model analyses showed the significant detrimental effect of prenatal lead exposure in late pregnancy on cognitive development up to 36 months in children of mothers having less dietary iron intake during pregnancy. Thus, our findings imply importance to reduce prenatal lead exposure and have adequate iron intake for better neurodevelopment in children. PMID- 26825888 TI - Malgaigne Fracture in Childhood: A Case Report and Review of Literature. AB - Sacrum fractures are rare pathologies seen after spinal traumas. The incidence of a sacral fracture after trauma is 0.6% in childhood. A Malgaigne fracture is composed of fractures and dislocations of the anterior and posterior regions of the pelvis. This is the first reported case of Malgaigne fracture during childhood. A 12-year-old girl was admitted to our emergency room after having suffered a fall. Radiological tests revealed a zone 3 sacral fracture according to the Denis scoring, a subtype 2 sacral fracture according to the Roy-Camille classification, and a detachment in the symphysis pubis. Appropriate load distribution through a bilateral L5-S1-S2 transpedicular screw and a bilateral iliac wing screw, as well as neural decompression were performed together with an S1-S2 total laminectomy. It is very difficult to make a generalization for treatment of sacral fractures and Malgaigne fractures in childhood due to the small number of patients. Each patient should be individualized and lumbosacroiliac instability should be treated. PMID- 26825889 TI - Adult-onset Nemaline Myopathy Coexisting With Myasthenia Gravis: A Case Report. AB - Myasthenia gravis (MG) is an autoimmune neuromuscular junction disorder which is characterized by fluctuating muscle fatigue. However, the association of MG with nemaline myopathy is rarely reported. Here we report a case of MG coexisting with adult-onset nemaline myopathy. A 55-year-old man endured fluctuating muscle weakness with positive acetylcholine receptor and titin antibodies. After the patient was administrated cholinergic drugs and immunosuppression, the muscle weakness of the patient had mildly been alleviated. Electromyography showed a progressive decrement in the amplitude of muscle action potential at low frequency. Muscle biopsy showed numerous nemalines in the muscle fibers. This is the first reported case of nemalines present in the muscle fibers of adult patient with MG. The pathogenesis of nemaline may be related to titin antibody in adult-onset nemaline myopathy with MG. PMID- 26825890 TI - The Case for Adolescent HIV Vaccination in South Africa: A Cost-Effectiveness Analysis. AB - Despite comprising 0.7% of the world population, South Africa is home to 18% of the global human immunodeficiency virus (HIV) prevalence. Unyielding HIV subepidemics among adolescents threaten national attempts to curtail the disease burden. Should an HIV vaccine become available, establishing its point of entry into the health system becomes a priority. This study assesses the impact of school-based HIV vaccination and explores how variations in vaccine characteristics affect cost-effectiveness. The cost per quality adjusted life year (QALY) gained associated with school-based adolescent HIV vaccination services was assessed using Markov modeling that simulated annual cycles based on national costing data. The estimation was based on a life expectancy of 70 years and employs the health care provider perspective. The simultaneous implementation of HIV vaccination services with current HIV management programs would be cost effective, even at relatively higher vaccine cost. At base vaccine cost of US$ 12, the incremental cost effectiveness ratio (ICER) was US$ 43 per QALY gained, with improved ICER values yielded at lower vaccine costs. The ICER was sensitive to duration of vaccine mediated protection and variations in vaccine efficacy. Data from this work demonstrate that vaccines offering longer duration of protection and at lower cost would result in improved ICER values. School-based HIV vaccine services of adolescents, in addition to current HIV prevention and treatment health services delivered, would be cost-effective. PMID- 26825891 TI - Polysplenia Syndrome With Splenic and Skeletal Muscle Metastases From Thyroid Carcinoma Evaluated by FDG PET/CT: Case Report and Literature Review: A Care Compliant Article. AB - Polysplenia syndrome (PSS) is a rare congenital abnormality. Metastases to spleen and skeletal muscle from differentiated thyroid cancer (DTC) are also extremely rare. Our case report aims to present an interesting case of PSS associated with splenic metastasis (SM) and skeletal muscle metastasis (SMM) from advanced papillary thyroid carcinoma which was evaluated on fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). An 84-year-old Chinese man was admitted with the history of multiple enlarged masses in bilateral neck, right axillary, and inguinal areas for >2 months. The results of ultrasonography examination were highly suggestive of malignancy. The histological results of the following biopsy were consistent with papillary thyroid carcinoma with involvement of multiple regional lymph nodes. He was referred for an FDG PET/CT imaging to evaluate the situation. FDG PET/CT showed that an intense FDG-avid thyroid mass with widespread regional lymph node involvement and distant metastases in the body. Unexpected sites of metastases were detected in the spleens and skeletal muscles. Most interestingly, FDG PET/CT imaging also described the typical imaging findings of PSS including the 2 right-sided spleens, azygos and hemiazygos continuation of inferior vena cava (IVC), right sided stomach, middle line liver, a short pancreas, preduodenal portal vein (PPV), and malrotation of gut. Whole body FDG PET/CT imaging can accurately evaluate the situation of DTC by detecting regional lymph node involvement, common and rare sites of distant metastases which are closely related to staging, management, and prognosis of this disease. Whole-body FDG PET/CT is also valuable in demonstrating the typical imaging features of PSS. PMID- 26825892 TI - Natural Transmission Model for Severe Fever With Thrombocytopenia Syndrome Bunyavirus in Villages of Hubei Province, China. AB - Severe fever with thrombocytopenia syndrome (SFTS), an emerging high-fatality infectious disease, is caused by a novel bunyavirus. However, a clear natural transmission model has not yet been established. We conducted a cross-sectional study with in-depth investigation of villages to systematically understand the transmission and risk factors among humans, host animals, and vectors. Village residents were interviewed using standardized questionnaires, in which there were confirmed cases of new infections, between August 2012 and May 2013. Serum samples from all villagers and animals, as well as tick specimens, were collected for qRT-PCR and antibody testing. The seropositivity rate among villagers was 8.4% (35/419), which was lower than that among domesticated animals (54.0%, 27/50; chi(2)= 81.1, P < 0.05). SFTS viral RNA was most commonly detected among domesticated animals (14.0%), followed by ticks (3.1%) and humans (1.7%; chi(2) = 23.1, P < 0.05). The homology of the S gene fragment was 98%. Tick bites were significantly associated with SFTSV infection (Conditional Logistic Regression odds ratio [OR] = 2.5, 95% confidence interval [CI], 1.0-6.6). We provided systematic evidence on a natural transmission model for SFTSV from reservoir hosts (domesticated animals) to vectors (Haemaphysalis longicornis) to humans, and close contact with SFTS confirmed patients was not found to be a risk factor for natural transmission. PMID- 26825893 TI - Rifaximin for Irritable Bowel Syndrome: A Meta-Analysis of Randomized Placebo Controlled Trials. AB - The current treatments for irritable bowel syndrome (IBS) are suboptimal. The findings of previous studies of rifaximin treatment for IBS may have differed due to variations in study design. Our study aimed to determine the therapeutic and adverse effects of rifaximin treatment for IBS based on a meta-analysis of published randomized controlled trials (RCTs). We searched the MEDLINE, EMBASE, EBSCO, Springer, Ovid, and Cochrane Library databases for RCTs investigating the effects of rifaximin on IBS. Data from each selected RCT was evaluated individually based on an intention-to-treat analysis, and a meta-analysis was performed in which the odds ratios (ORs) and 95% confidence intervals (CIs) of clinical outcomes and adverse events were calculated using fixed-effects models. Four eligible studies were identified. Overall relief of IBS symptoms in the rifaximin groups was greater than that in the placebo groups at the ends of both the treatment and follow-up periods (OR = 1.19; 95% CI: 1.08-1.32 and OR = 1.36; 95% CI: 1.18-1.58, respectively, P < 0.05 for both). Significant relief of abdominal distention was observed at the follow-up endpoint (OR = 1.69; 95% Cl: 1.27-2.23; P < 0.05), but not at the treatment endpoint (OR = 1.19; 95% CI: 0.96 1.49; P > 0.05). Abdominal pain (OR = 1.01; 95% CI: 0.98-1.03; P > 0.05), nausea (OR = 1.00; 95% CI: 0.98-1.02; P > 0.05), vomiting (OR: 0.99; 95% CI: 0.98-1.01; P > 0.05), and headache (OR = 1.01; 95% CI: 0.98-1.03; P > 0.05) did not differ significantly between the rifaximin and placebo groups. In the RCTs selected, our meta-analysis showed that the efficacy of rifaximin for the resolution of overall IBS symptoms was greater than that of the placebos, and that rifaximin was well tolerated. The course of relief from abdominal distention in IBS patients treated with rifaximin may be delayed in some patients, compared with that of overall IBS symptom relief. PMID- 26825894 TI - Safety and Efficacy of EUS-Guided Ethanol Ablation for Treating Small Solid Pancreatic Neoplasm. AB - The strategy for treating small borderline malignant pancreatic neoplasms--such as neuroendocrine tumor (NET) and solid pseudopapillary neoplasm (SPN)--is surgical resection. However, pancreatic resection of these lesions still causes significant morbidity. We evaluated the safety and efficacy of EUS-guided ethanol ablation to treat small solid pancreatic neoplasms. A total of 8 patients with small borderline malignant pancreatic neoplasms and co-morbidities who refused surgery were included. We identified 2 cases of nonfunctioning NET, 3 cases of insulinomas, 1 case of gastrinoma, and 2 cases of SPN. EUS-guided ethanol ablation was performed, and treatment outcomes were assessed with clinical symptom, hormone assay, and imaging study. The mean tumor diameter was 15 mm (range, 7-29 mm), and the median volume of injected ethanol was 2.8 mL (range, 1.2-10.5 mL). There was 1 severe acute pancreatitis after EUS-guided ethanol ablation with 20-gauge CPN needle. During follow-up (median 16.5 months), 6 patients achieved treatment success; however, 2 patients (1 nonfunctioning NET and 1 SPN) still had persistent tumors. The patient with persistent SPN underwent surgical resection and the histopathological results showed peripancreatic infiltration with perineural invasion. Among 6 patients who achieved initial treatment success, 1 patient experienced tumor recurrence within 15 months and underwent repeated EUS-guided ethanol ablation. In conclusion, EUS-guided ethanol ablation therapy is a promising option for patients with small solid pancreatic neoplasm. Multiple sessions or surgical interventions may be required if there is a recurrent or persistent mass, and procedure-related adverse events must be carefully monitored. PMID- 26825895 TI - Endovascular Management of May-Thurner Syndrome: A Case Report. AB - May-Thurner syndrome (MTS) is caused by venous occlusion because of compression of the iliac vein by the iliac artery and vertebral body, leading to left lower extremity deep venous thrombosis, eventually resulting in a series of symptoms. Endovascular treatment has now become the most preferred method of treatment of MTS. The authors report a 66-year-old woman who was hospitalized because of increasing swelling in her left lower limb for almost 2 weeks. Ultrasonography performed upon admission indicated MTS, and venography revealed occlusion of the left common iliac vein and massive thrombosis in the left external iliac and femoral veins. The left lower extremity venous blood flow returned to normal after the patient underwent manual aspiration thrombectomy using a guide catheter, followed by balloon angioplasty and stent placement. The patient achieved complete remission after 1 week and had no in-stent restenosis during the 1-year follow-up. Endovascular treatment is a safe and effective treatment of MTS. PMID- 26825897 TI - Does High-Dose Cytarabine Cause More Fungal Infection in Patients With Acute Myeloid Leukemia Undergoing Consolidation Therapy: A Multicenter, Prospective, Observational Study in China. AB - Invasive fungal infection (IFI) remains as a significant cause of morbidity and mortality in patients with acute myelogenous leukemia (AML). Here, we report the subgroup analysis of China Assessment of Antifungal Therapy in Haematological Disease (CAESAR) study to evaluate the risk of IFI in patients with AML in 1st remission receiving high-dose cytarabine (HiDAC) as consolidation. A total of 638 patients with AML in 1st complete remission were selected from the database. Among them, 130 patients received HiDAC alone with total dose of 2-3 g/m(2) * 6 while 508 patients received multiple-agent combination chemotherapy (multiagent chemo group). The patients' characteristics were generally not different but more patients in HiDAC group had peripherally inserted central catheter (61.5% vs 44.5%, P = 0.002). The median duration of neutropenia was 8.0 days in both HiDAC (2-20) and multiagent chemo group (2-28). Number of patients with prolonged neutropenia (>14 days) tended to be more in multiagent chemo group but not significant different (16.3% vs 8.8%, respectively). There was no significant difference between 2 groups in persistent neutropenic fever (40.8% vs 33.1%), antifungal treatment (11.5% vs 11.4%), and incidence of proven/probable IFI (4 probable in HiDAC vs 1 proven/4 probable in multiagent chemo, P = 0.35) or possible IFI. As to the clinical outcome in terms of duration of hospitalization and death in remission, there was a trend of shorter duration of hospitalization in HiDAC (19 days, 3-70) compare to multiagent chemo group (21 days, 1-367, P = 0.057) while no death documented in HiDAC group and only 2 patients died in the multiagent chemo group (0.4%). As to risk factors associated with IFI in all 638 patients, there was a trend of more IFI in patients with severe neutropenia (3.0%, P = 0.089) and previous history of IFI (3.85%, P = 0.086) while the antifungal prophylaxis was not associated significantly reduced IFI. Overall, our data support the perception that HiDAC alone as consolidation in first remission AML patients was well tolerated and not associated with increased hematological toxicity and IFI than conventional combination chemotherapy. Antifungal prophylaxis may not necessary except for patients with previous history of IFI. PMID- 26825896 TI - Fruit and Vegetable Intake in Relation to Lower Urinary Tract Symptoms and Erectile Dysfunction Among Southern Chinese Elderly Men: A 4-Year Prospective Study of Mr OS Hong Kong. AB - The role of fruit and vegetable (FV) intake in relation to prostate health remains inconclusive. This 4-year longitudinal study aims to explore the association of FV intake and the development of lower urinary tract symptoms (LUTS, a cluster of chronic urinary symptoms occurring in bladder, prostate and urethra), incidence of symptomatic benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) in Chinese elderly men. Data were obtained from a 4 years longitudinal study (Mr OS Hong Kong, the largest prospective study on bone health in Chinese elderly). Two thousand Chinese men aged 65 years and older were recruited from the local community, of whom 1998 (99.9%) at baseline and 1564 (78.2%) at 4-year follow-up reported data on LUTS, which were evaluated by a validated International Prostate Symptoms Scale (IPSS). Erectile function was evaluated by the International Index of Erectile Dysfunction-5 (IIEF-5) questionnaires at 2- (n = 386) and 4-year (n = 475) follow-ups. Dietary intake was assessed using a validated food frequency questionnaire at baseline. Analysis was conducted using multivariate linear and logistic regression. For total FV and most of their subclasses, moderate consumption had the lowest mean changes of LUTS; we thus applied the moderate levels as the reference in the regression models. The high levels of total FV intake (>350 g/1000 kcal/day) were significantly associated with reduced IPSS by scores of -1.174 +/- 0.459 (or 17.3% of basal IPSS, P = 0.011) relative to the moderate groups (250-350 g/1000 kcal/day). FV consumption had no significant association with the score change of ED or the odds of sexual activities at 4-year (all P > 0.05). High intake of dark and leafy vegetables (>50 g/1000 kcal/day) significantly reduced the risk of LUTS progression by 37.2% [odds ratio (OR) (95% confidence interval, 95% CI): 0.628 (0.466~0.848), P = 0.002] or risk of symptomatic BPH by 34.3% [OR (95% CI): 0.657 (0.442-0.976), P = 0.038] after 4 years compared with the moderate group (25-50 g/1000 kcal/day). Adequate FV intakes, especially dark and leafy vegetables, were associated with improved LUTS among Chinese elderly men, but lack an association with ED and sexuality. PMID- 26825898 TI - Association Between Leptin (-2548G/A) Genes Polymorphism and Breast Cancer Susceptibility: A Meta-Analysis. AB - Leptin is a confirmed breast cancer susceptibility gene. However, published studies reported mixed results. This meta-analysis was conducted to systematically get a more accurate estimation of the association between the Leptin (-2548G/A) gene polymorphism and breast cancer risk. To assess the effect of Leptin (-2548G/A) gene polymorphism on breast cancer susceptibility, we searched PUBMED, ISI Web of Knowledge, EMBASE, Chinese National Knowledge Infrastructure (CNKI) databases until September 2015 to identify eligible studies, without restriction. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to breast cancer. Separate analyses were conducted on features of the population such as ethnicity, source of controls, and country. A total of 9 case-control studies on Leptin ( 2548G/A) gene polymorphism and breast cancer risk, including 3725 cases and 3093 case-free controls were identified. The results revealed that compared with the G allele, the A allele was associated with modestly increased risk of overall breast cancer (A vs G: OR = 1.12, 95%CI = 1.04-1.20, P = 0.002, Phet P < 0.00001). Following further stratified analyses, in the subgroup analyses by ethnicity, a significantly increased risk was observed among Caucasian (A vs G: OR = 1.11, 95%CI = 1.03-1.20, P = 0.006, Phet = 0.00001). No publication bias was found in the present study. In conclusion, our meta-analysis suggests that the Leptin (-2548G/A) gene polymorphism plays an important role in breast cancer susceptibility, especially in Caucasian. PMID- 26825899 TI - Comparison of Clinical Efficacy Between Interlaminar and Transforaminal Epidural Injection in Patients With Axial Pain due to Cervical Disc Herniation. AB - Transforaminal (TF) approach is preferred by physician to interlaminar (IL) approach because it can deliver injectates directly around nerve root and dorsal root ganglion, which is regarded as main pain sources. Axial neck pain is originated from sinuvertebral nerve located in ventral epidural spaces, which has been described to be related to central or paramedian disc herniation. It is very questionable that TF injection is also more effective than IL injection in the patients with axial neck or interscapular pain. This study was to evaluate clinical efficacy of cervical epidural injection in patients with axial pain due to cervical disc herniation and to compare the clinical outcomes between TF and IL approaches. Fifty-six and 52 patients who underwent IL and TF epidural injections, respectively, for axial neck/interscapular pain due to central or paramedian cervical disc herniation were included. Numeric Rating Scale (NRS) and Neck Disability Index (NDI) were compared between both groups at 2 and 8 weeks after treatment. Successful pain relief was defined if a 50% or more reduction of NRS score was achieved in comparison with pretreatment one. Successful functional improvement was defined if at least a 40% reduction of NDI was obtained. Overall, 79 (73.1%) and 57 (52.8%) among 108 patients showed successful pain relief at 2 and 8 weeks, respectively. Seventy-six (70.4%) and 52 (48.1%) had successful functional improvement at 2 and 8 weeks, respectively. The IL and TF groups showed no significant difference in proportion of successful results of NRS 2 weeks (73.2% vs 67.3%) and 8 weeks (48.2% vs 48.1%). Also, no significant difference was obtained in proportion of successful NDI between 2 groups at 2 weeks (75.0% vs 71.2%) and 8 weeks (53.6% vs 51.9%). Cervical epidural injection showed favorable results in 2 weeks and moderate results in 8 weeks in patients with axial pain due to cervical disc herniation. IL and TF showed no significant difference in clinical efficacy. Considering TF was relevant to more serious side effects, IL was more recommendable in these patients. PMID- 26825900 TI - Histogram Analysis of Apparent Diffusion Coefficient in Differentiating Pancreatic Adenocarcinoma and Neuroendocrine Tumor. AB - The aim of this study was to investigate whether histogram analysis in diffusion weighted (DW) magnetic resonance imaging (MRI) can help differentiate pancreatic adenocarcinomas from neuroendocrine tumors.Sixty-four patients with histologically confirmed 53 pancreatic adenocarcinomas or 19 neuroendocrine tumors underwent DW MRI. We evaluated the pixel distribution histogram parameters (mean, skewness, kurtosis, and entropy) of the apparent diffusion coefficient (ADC) values derived from b-values of 0 and 200 (ADC200), 0 and 400 (ADC400), or 0 and 800 (ADC800) s/mm(2). Histogram parameters were compared between pancreatic adenocarcinomas and neuroendocrine tumors, and the diagnostic performance was evaluated by using receiver operating characteristic (ROC) analysis.The mean ADC200 and ADC400 were significantly higher in neuroendocrine tumors than in pancreatic adenocarcinomas (P = 0.001 and P = 0.019, respectively). Pancreatic adenocarcinomas showed significantly higher skewness and kurtosis on ADC400 (P = 0.007 and P = 0.001, respectively) and ADC800 (P = 0.001 and P = 0.001, respectively). With all b-value combinations, the entropy of ADC values was significantly higher in pancreatic adenocarcinomas (P < 0.001 for ADC200; P = 0.001 for ADC400; P < 0.001 for ADC800), and showed the highest area under the ROC curve for diagnosing adenocarcinomas (0.77 for ADC200, 0.76 for ADC400, and 0.78 for ADC800).ADC histogram analysis of DW MRI can help differentiate pancreatic adenocarcinomas from neuroendocrine tumors. PMID- 26825901 TI - Comparative Efficacy and Safety of Prostacyclin Analogs for Pulmonary Arterial Hypertension: A Network Meta-Analysis. AB - Prostacyclin analogs, such as epoprostenol, treprostinil, iloprost, and beraprost, have long been used for pulmonary arterial hypertension (PAH) treatment, yet their relative efficiency remains disputed. Eligible randomized controlled trials (RCTs) involving the 4 therapies mentioned above were retrieved from PubMed, Embase, and Cochrane (up to August 1, 2015). Odds ratios (ORs) were estimated for dichotomous data (mortality, functional class (FC) amelioration, and discontinuation); standardized mean differences (SMDs) with 95% confidence intervals (CIs) were estimated for continuous data (6-min walk distance [6-MWD]). Patients taking epoprostenol were anticipated to demonstrate more expedient 6-MWD than those taking placebo when network meta-analysis (NMA) was implemented (SMD = 52.19; 95% CI: 24.28-113.39), the trend of which was identical with that of pairwise meta-analysis (SMD = 69.28; 95% CI: 10.43-128.98). Nonetheless, the prominent advantages of treprostinil over placebo (SMD = 30.15; 95% CI: 19.29 40.01) in 6-MWD could not be replicated by NMA. Furthermore, direct and indirect (NMA) comparisons also differed in FC amelioration. For example, the superiority of epoprostenol over placebo as evident with the use of NMA (OR = 42.79; 95% CI: 10.63-301.98) could not be confirmed by pairwise meta-analysis. As suggested by indirect comparisons among 4 prostanoids, epoprostenol appears to result in remarkably favorable FC amelioration comparing to other regimens (all P < 0.05). Participants taking beraprost were more probable to withdraw in comparison with those administrated with iloprost (OR = 10.07; 95% CI: 1.47-160.65). Taking mortality, FC amelioration, discontinuation, and 6-MWD into account, epoprostenol could be recommended as an alternative treatment for patients with moderate/advanced PAH. PMID- 26825902 TI - White Matter Microstructural Integrity and Neurobehavioral Outcome of HIV-Exposed Uninfected Neonates. AB - The successful implementation of prevention programs for mother-to-child human immunodeficiency virus (HIV) transmission has dramatically reduced the prevalence of infants infected with HIV while increasing that of HIV-exposed uninfected (HEU) children. Neuropsychological assessments indicate that HEU children may exhibit differences in neurodevelopment compared to unexposed children (HUU). Pathological mechanisms leading to such neurodevelopmental delays are not clear. In this observational birth cohort study we explored the integrity of regional white matter microstructure in HEU infants, shortly after birth. Microstructural changes in white matter associated with prenatal HIV exposure were evaluated in HEU infants (n = 15) and matched controls (n = 22) using diffusion tensor imaging and tract-based spatial statistics. Additionally, diffusion values were extracted and compared for white matter tracts of interest, and associations with clinical outcomes from the Dubowitz neonatal neurobehavioral tool were investigated. Higher fractional anisotropy in the middle cerebellar peduncles of HEU compared to HUU neonates was found after correction for age and gender. Scores on the Dubowitz abnormal neurological signs subscale were positively correlated with FA (r = 0.58, P = 0.038) in the left uncinate fasciculus in HEU infants. This is the first study to present data suggesting that prenatal HIV exposure without infection is associated with altered white matter microstructural integrity in the neonatal period. Longitudinal studies of HEU infants as their brains mature are necessary to understand further the significance of prenatal HIV and antiretroviral treatment exposure on white matter integrity and neurodevelopmental outcomes. PMID- 26825903 TI - Clinicopathologic Characteristics and Outcomes of Lupus Nephritis With Antineutrophil Cytoplasmic Antibody: A Retrospective Study. AB - Few studies have analyzed the clinicopathologic characteristics and outcomes of lupus nephritis (LN) patients with antineutrophil cytoplasmic antibody (ANCA). The clinical and renal histopathologic data of 154 patients with biopsy-proven LN from 2011 to 2013 were analyzed retrospectively. The patients were followed up for a median period of 16.8 +/- 9.4 months, and their outcomes were analyzed. Multivariate Cox analysis was used to evaluate the independent factors for poor outcomes. Among the 154 LN patients, 26 (16.88%) were seropositive for ANCA. The incidences of alopecia, oral ulcer, photosensitivity and skin lesion, and psychosomatic manifestations in the ANCA-positive group were significantly higher than in the ANCA-negative group (P = 0.007, 0.02, 0.02, and 0.03, respectively). Compared with the ANCA-negative group, the ANCA-positive group had significantly lower levels of complement C3 (P = 0.03). Additionally, the positive rate of antinucleosome antibodies, antihistone antibodies, antimitochondrial antibody M2, and anticardiolipin antibodies were higher significantly in the ANCA-positive patients than in the ANCA-negative patients (P = 0.001, 0.001, 0.03, 0.005, respectively). The ANCA-positive group had a notably higher chronic index than the ANCA-negative group (P = 0.01). During the follow-up, the complete remission rate in the ANCA-negative group was higher than that in the ANCA-positive group (P = 0.01). The cumulative renal survival rate in the ANCA-positive group was significantly lower than in the ANCA-negative group (log-rank = 6.59, P = 0.01). Multivariate Cox analysis revealed that the reduced estimated glomerular filtration rate (HR, 1.02; 95% confidence interval, 1.01 to 1.03; P = 0.005), NLR (HR, 1.20; 95% confidence interval, 1.02 to 1.40; P = 0.03), and ANCA (HR, 3.37; 95% confidence interval, 1.12 to 10.09; P = 0.03) were independent risk factors for patients' renal survival after adjusting for age, sex, crescent formation, and glomerulosclerosis. The study found ANCA in LN patients is not rare, and patients with ANCA present with more severe clinicopathologic injuries. Thus, ANCA is an independent risk factor for poor renal outcomes in LN patients. PMID- 26825904 TI - Comparison of Sagittal Spinopelvic Alignment in Patients With Ankylosing Spondylitis and Thoracolumbar Fracture. AB - This article is a comparative study. The aim of the study is to investigate the difference of sagittal alignment of the pelvis and spine between patients with thoracolumbar kyphosis secondary to ankylosing spondylitis (AS) and thoracolumbar fracture, and to evaluate the role of sacropelvic component in AS patients' adaption to the changes in sagittal alignment. Advanced stages of AS are often associated with thoracolumbar kyphosis, resulting in an abnormal spinopelvic balance and pelvic morphology, whereas thoracolumbar fractures may lead to major kyphosis with a potential compromise of the spinal canal, which can cause an abnormal spinopelvic balance. Until now, the comparison of that sagittal alignment between AS and thoracolumbar fracture is not found in the literature. This study included 30 cases of AS and 30 cases of thoracolumbar fracture. Sagittal spinal and pelvic parameters were measured from the standing lateral radiograph, and the following 11 radiological parameters were measured, including global kyphosis (GK), thoracic kyphosis (TK), C7 tilt (C7T), sagittal vertical axis (SVA), spino-pelvic angle (SSA), lumbar lordosis (LL), upper arc of lumbar lordosis (ULL), lower arc of lumbar lordosis (LLL), pelvic incidence (PI), sacrum slope (SS), pelvic tilt (PT), and T9 tilt (T9T). Analysis of variance was used in the comparison of each dependent variable between the 2 cohorts. The relationship between sagittal spinal alignment and pelvic morphology of AS patients was determined via Pearson correlation coefficient (r). Compared with the thoracolumbar fracture group, AS patients had significantly lower C7T, SSA, LL, LLL and SS (78.3 degrees +/- 9.3 degrees vs 88.0 degrees +/- 2.7 degrees , P < 0.001 for C7T; 91.6 degrees +/- 22.7 degrees vs 119.1 degrees +/- 9.0 degrees , P < 0.001 for SSA; 20.7 degrees +/- 21.0 degrees vs 36.3 degrees +/- 16.8 degrees , P = 0.001 for LL; 18.1 degrees +/- 11.9 degrees vs 29.0 degrees +/- 9.7 degrees , P < 0.001 for LLL; and 18.1 degrees +/- 11.9 degrees vs 29.0 degrees +/- 9.7 degrees , P < 0.001 for SS), whereas in terms of SVA and PT, AS patients had an obviously higher value than those of thoracolumbar fracture patients (94.5 mm +/- 58.4 mm vs 8.0 mm +/- 23.3 mm, P < 0.001 for SVA; and 26.5 degrees +/- 10.3 degrees vs 17.5 degrees +/- 6.6 degrees , P < 0.001 for PT). In AS patients, SS were found to be significantly correlated with SVA, SSA, and LL (r = -0.312, P < 0.05 for SVA; r = 0.475, P < 0.05 for SSA; r = 0.809, P < 0.001 for LL). In our study, there were significant differences in sagittal alignment of the pelvis and spine between patients with AS and thoracolumbar fracture, and changes in pelvic morphology compensated more in AS patients for a thoracolumbar kyphosis. These findings may be helpful for better understanding of sagittal alignment in patients with thoracolumbar kyphosis secondary to AS. PMID- 26825905 TI - Reduced NM23 Protein Level Correlates With Worse Clinicopathologic Features in Colorectal Cancers: A Meta-Analysis of Pooled Data. AB - The clinical value of a prominent metastasis suppressor, nonmetastatic protein 23 (NM23), remains controversial. In this study, we examined the correlation between NM23 protein levels and the clinicopathologic features of colorectal cancers (CRC), and assessed the overall prognostic value of NM23 for CRC. Embase, PubMed, Web of Science, and other scientific literature databases were exhaustively searched to identify relevant studies published prior to June 31, 2015. The methodological qualities of selected studies were scored based on the critical appraisal skills program (CASP) criteria, as independently assessed by 2 reviewers. NM23 protein levels in tumor tissues of CRC patients were examined in relation to Dukes stage, differentiation grade, T-stage, lymph node metastasis status, and overall survival (OS). STATA software version 12.0 (Stata Corp, College Station, TX) was used for statistical analysis of data pooled from selected studies. Nineteen cohort studies met the inclusion criteria for present study and contained a combined total of 2148 study subjects. Pooled odd ratios (ORs) for NM23 expression revealed that reduced NM23 protein levels in CRC tumor tissues correlated with Dukes stage C and D (OR = 1.89, 95% CI: 1.06-3.39, P = 0.032), poor differentiation grades (OR = 1.41, 95% CI: 1.03-1.94, P = 0.032), and positive lymph node metastasis status (OR = 3.21, 95% CI: 1.95-5.29, P < 0.001). On the other hand, no such correlations were evident with T-stage T3-4 (OR = 1.56, 95% CI: 0.60-4.06, P = 0.367) or OS (OR = 0.79, 95% CI: 0.58-1.08, P = 0.138). Our analysis of pooled data found that NM23 expression is reduced in CRC tissues and low NM23 levels tightly correlate with higher Dukes stages, poorer differentiation grade, and positive lymph node metastases. However, NM23 levels did not influence the OS in CRC patients. PMID- 26825906 TI - A Model for Predicting the Future Risk of Incident Erosive Esophagitis in an Asymptomatic Population Undergoing Regular Check-ups. AB - Erosive esophagitis is a major risk factor for Barrett esophagus and esophageal adenocarcinoma. Information regarding the putative risk factors for developing erosive esophagitis is considerably heterogeneous; thus, a risk model is required to clinically predict the incidence of erosive esophagitis. This study was to derive and validate a predictive model for the incidence of developing erosive esophagitis after negative index endoscopy in a population subjected to routine health check-ups. This retrospective cohort study of health check-ups included 11,535 patients who underwent repeated screening endoscopy after >3 years from a negative index endoscopy. We used logistic regression analysis to predict the incidence of erosive esophagitis, and a Simple Prediction of Erosive Esophagitis Development score for risk assessment was developed and internally validated using the split-sample approach. The development and validation cohorts included 5765 patients (675 with erosive esophagitis [11.7%]) and 5770 patients (670 with erosive esophagitis [11.6%]), respectively. The final model included sex, smoking behavior, body mass index, hypertension, and the triglyceride level as variables. This model predicted 667 cases of erosive esophagitis, yielding an expected-to observed ratio of 1.00 (95% confidence interval [CI], 0.92-1.07). A simplified 5 item risk scoring system based on coefficients was developed, with a risk of erosive esophagitis of 6.2% (95% CI, 5.2-7.1) for the low-risk group (score <=2), 15.1% (95% CI, 13.5-16.6) for the intermediate-risk group (score <=3, 4), and 18.2% (95% CI, 15.2-21.3) for the high-risk group (score >=5). The discriminative performance of the risk-prediction score was consistent in the derivation cohort and validation cohort (c-statistics 0.68 and 0.64, respectively); the calibration was good (Brier score 0.099 and 0.1, respectively). In conclusion, a simple risk scoring model using putative risk factors can predict the future incidence of developing erosive esophagitis in asymptomatic populations. PMID- 26825907 TI - Relationship of Focally Amplified Long Noncoding on Chromosome 1 (FAL1) lncRNA with E2F Transcription Factors in Thyroid Cancer. AB - Recent functional genomic studies revealed that the oncogenic activity of focally amplified lncRNA on chromosome 1 (FAL1, ENSG00000228126) contributes to tumor growth by p21 repression in human cancers. However, the expression of FAL1 was not investigated in papillary thyroid cancer (PTC). We aimed to determine if FAL1 was up-regulated in PTC compared to paired contralateral normal thyroid tissues, and to investigate the potential targets of this lncRNA and its clinicopathological significance in PTC. We analyzed FAL1 and p21 expression levels in 100 PTC samples and matched normal thyroid tissue by qRT-PCR. Using lncRNA microarray data from the Gene Expression Omnibus (accession no. GSE61763), we explored potential targets of FAL1 by Gene Set Enrichment Analysis, followed by verification by qRT-PCR in our PTC samples. A cross-sectional observational study was conducted to investigate the relationship between patients' clinicopathological features and FAL1 expression. FAL1 expression was significantly higher in PTC than in paired normal thyroid tissues (paired t test, P < 0.001). p21 mRNA expression was also increased, not decreased, in PTC, and had no correlation with FAL1 expression (r = 0.0897, P = 0.4002). Gene Set Enrichment Analysis, using publicly available microarray data, indicated that a gene set related to the cell cycle, including E2F transcription factors 1 and 2, and cyclin D1, was coordinately enriched among samples with high FAL1 expression. A volcano plot showed that E2F1, E2F2, and VEGFA mRNAs were increased in the high FAL1 samples. In clinicopathological analyses, multifocality was more frequently observed in PTC patients with high FAL1 (P = 0.018). Multivariate analysis showed that high FAL1 expression increased the risk of multifocality (after adjustment for clinical variables, OR = 4.019, CI = 1.041-11.020, P = 0.043). FAL1 may have a role in cell-cycle progression and may be associated with aggressive tumor behavior in PTC. PMID- 26825908 TI - Platelet-to-Lymphocyte Ratio: A Novel Prognostic Factor for Prediction of 90-day Outcomes in Critically Ill Patients With Diabetic Ketoacidosis. AB - Diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes mellitus and the novel systemic inflammation marker platelet-to-lymphocyte ratio (PLR) may be associated with clinical outcome in patients with DKA. This study aimed to investigate the utility of PLR in predicting 90-day clinical outcomes in patients with DKA. Patient data exacted from the Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC II) database was analyzed. A cutoff value for PLR of 267.67 was determined using Youden index (P < 0.05) and used to categorize subjects into a high PLR group and a low PLR group. The hazard ratios (HRs) and 95% confidence intervals (CIs) for DKA were calculated across PLR. Clinical outcomes in our study were defined as intensive care unit (ICU) 90-day readmission and all-cause mortality. A total of 278 ICU admissions were enrolled and stratified by cutoff value of PLR. The incidence of readmission and mortality was 17.8% in the high PLR group, significantly higher than 7.4% in the low PLR group. In the multivariable model, after adjusting for known confounding variables including clinical parameters, comorbidities, laboratory parameters, the HRs for DKA were 2.573 (95% CI 1.239-5.345; P = 0.011), 2.648 (95% CI 1.269 5.527; P = 0.009), and 2.650 (95% CI 1.114-6.306; P = 0.028), respectively. The Kaplan-Meier survival curve showed that a high PLR level was associated with a higher risk for 90-day outcomes in patients with DKA. The authors report that higher PLR presents a higher risk for 90-day incidence of readmission and mortality in patients with DKA. It appears to be a novel independent predictor of 90-day outcomes in critically ill DKA patients in ICU units. PMID- 26825909 TI - A Large Cohort Study on the Clinical Value of Simultaneous Amplification and Testing for the Diagnosis of Pulmonary Tuberculosis. AB - The AmpSure simultaneous amplification and testing method for the detection of Mycobacterium tuberculosis (SAT-TB assay) was designed to diagnose rapidly pulmonary tuberculosis (PTB). Unfortunately, the diagnostic advantage is unclear from previous small sample studies. In the current inquiry, a large sample size was used to reevaluate the clinical accuracy of the SAT-TB assay using sputum specimens. A total of 3608 patients with suspected PTB were enrolled prospectively for diagnosis from sputum specimens using the SAT-TB assay. Of these, 2457 had a definite diagnosis of PTB confirmed by positive microbiology, or pathologic findings of TB in the lung, or clinical diagnosis of active PTB following anti-TB treatment with a favorable response. The sensitivity, specificity and accuracy of the SAT-TB assay were 75.8%, 100%, and 80.2%, respectively. The sensitivity of SAT-TB was significantly higher than that of the sputum smear (23.8%) (X(2) = 1327.437; P = 0.000), wheresa significantly lower than that of sputum culture (89.0%) (X(2) = 148.197; P = 0.000). The specificity of SAT-TB was significantly higher than that of sputum smears (96.3%) (X(2) = 20.375, P = 0.000), whereas no significant difference was found compared with sputum cultures (99.6%) (X(2) = 2.004, P = 0.500). Positive results in the SAT-TB assay using sputum specimens indicates that active PTB is present and anti-TB treatment is strongly recommended regardless of smear and culture test results. Simultaneous amplification and testing method for detection of Mycobacterium tuberculosis is an accurate, cheap, and rapid method for PTB diagnosis. PMID- 26825910 TI - Large HDL Subfraction But Not HDL-C Is Closely Linked With Risk Factors, Coronary Severity and Outcomes in a Cohort of Nontreated Patients With Stable Coronary Artery Disease: A Prospective Observational Study. AB - High-density lipoprotein (HDL) is highly heterogeneous in its size and composition. Till now, the link of HDL subfractions to coronary risk is less clear. We aimed to investigate the associations of HDL subfractions with traditional risk factors (RFs), coronary severity, and outcomes in a cohort of nontreated patients with stable coronary artery disease (CAD). We prospectively enrolled 591 eligible patients. Baseline HDL subfractions were separated by Lipoprint system. HDL subfractions (large, medium, and small) and HDL-cholesterol (HDL-C) levels were dichotomized into low and high group according to the 50 percentile. Coronary severity was evaluated by SYNTAX, Gensini, and Jeopardy scoring systems. Patients were followed up annually for major adverse cardiovascular events (MACEs). Cox proportional hazards' models were used to evaluate the risk of HDL subfractions on MACEs. Patients with high large HDL-C levels had a decreased number of RFs. Significantly, large HDL-C levels were negatively associated with coronary severity assessed by SYNTAX and Gensini score (both P < 0.05). New MACEs occurred in 67 (11.6%) patients during a median 17.0 months follow-up. Moreover, the log-rank test revealed that there was a significant difference between high and low large HDL-C groups in event-free survival analysis (P = 0.013), but no differences were observed in total HDL-C groups and medium or small HDL-C groups (both P > 0.05). In particular, the multivariate Cox-proportional hazards model revealed that high large HDL-C was associated with lower MACEs risk (hazard ratio [95% confidence interval] 0.531 [0.295-0.959]) independent of potential confounders. Higher large HDL-C but not medium, small, or total HDL-C is associated with lower cardiovascular risk, highlighting the potential beneficial of HDL subfractionation. PMID- 26825911 TI - STROBE-compliant article: Blood Transfusions within the First 24 Hours of Hospitalization Did Not Impact Mortality Among Patients with Severe Sepsis. AB - Transfusion of packed red blood cells is common during resuscitation of critically ill patients. However, the association between in-hospital mortality and blood transfusion among patients with severe sepsis during the first 24 hours of hospitalization has not yet been determined. A cohort study was conducted of adult nontrauma patients who visited the emergency department of a tertiary hospital and were diagnosed with severe sepsis. Propensity score (PS) matching was conducted, based on patient demographics, underlying illnesses, laboratory results, and vital signs presented at the emergency department, and multivariate logistic regression was performed to adjust for potential residual confounding between the 2 transfused and nontransfused groups to assess the risk of in-hospital mortality. Of 3448 patients included in this study, 265 underwent blood transfusion during the first 24 hours of hospitalization. Despite comparable severity of sepsis, patients who received transfusions tended to have lower mean arterial pressures (86 vs 98 mmHg) and hemoglobin levels (7.6 vs 11.2 g/dL), and were more likely to have chronic kidney disease (12% vs 6%) and hematologic organ dysfunction (57% vs 35%, all P < 0.001). Transfused patients tended to have higher mortality rates (26% vs 9%, respectively, P < 0.001). After PS matching, 177 pairs of transfused and nontransfused patients were analyzed. After adjusting for residual confounding factors by multivariate logistic regression in the matched patient pairs, no significant differences in in hospital mortality were observed (odds ratio [OR] = 1.52, 95% confidence interval: 0.92-2.51). In this PS-matched cohort study of adult nontrauma patients with severe sepsis, the in-hospital mortality rate was not significantly different in patients who received blood transfusions during the first 24 hours of hospitalization. PMID- 26825912 TI - Feasibility and Validation of Single-Port Laparoscopic Surgery for Simple Adhesive or Nonadhesive Ileus. AB - A single incisional laparoscopic surgery (SILS) approach is increasingly being used, taking advantage of the minimally invasive technique. The aim of this study was to evaluate the feasibility and the validation of SILS procedure for small bowel obstruction (SBO). Sixteen consecutive patients with SBO who underwent SILS release of ileus between April 2010 and March 2015 were compared with the conventional multiport laparoscopic treatment group of 16 patients matched for age, gender, and surgical procedure. Laparoscopic treatment was completed in a total of 14 patients in SILS group and 13 in multiport laparoscopic group. Two cases and 3 cases were converted to multiport laparoscopic surgery or open surgery. Eight patients with nonscar and nonadhesive ileus, such as internal hernia, obturator hernia, gallstone ileus, and intestinal invagination, were treated successfully in the laparoscopic procedure. There was no mortality in either of the groups. The mean procedural time was 105 minutes in the SILS group and 116 minutes in the multiport laparoscopic group. The mean amount of blood loss was not statistically different in either of groups (15 ml vs. 23 ml). Patients resumed oral intake after a mean of 2 days in the SILS and 3 days in the multiport groups with the statistically difference. The length of hospital stay was shorter in the SILS group (5 days vs. 7 days) with no statistically difference. Perioperative morbidity was seen in 2 patients in the SILS group and 3 patients in the multiport group. SILS approach has superior and/or similar perioperative outcomes to multiport approach for SBO. SILS release of ileus as an ultra-minimal invasion technique is feasible, effective, and offers benefits with cosmesis in simple adhesive or scar-less nonadhesive ileus patients. PMID- 26825913 TI - Dry Eye Syndrome Risks in Patients With Fibromyalgia: A National Retrospective Cohort Study. AB - The coexistence of fibromyalgia (FM) and dry eye syndrome (DES) has been previously reported. However, there are few studies on how patients with FM may develop concomitant DES. Patients with chronic widespread pain, like FM, chronic fatigue syndrome, and irritable bowel syndrome (IBS), was concerned for the rheumatic or psychosomatic disorders which might adequately reflect the long-term risk of DES. We retrieved data on FM patients from the National Health Insurance Research Database of Taiwan covering the years 2000 to 2011. Our FM population consisted of 25,777 patients versus 103,108 patients in the non-FM group: the overall incidence of DES in these populations was 7.37/10,000 and 4.81/10,000, respectively. Male FM patients had a higher incidence of DES, with a 1.39-fold DES risk for males and a 1.45-fold for females after adjustment for confounding factor. Notably, FM patients aged <=49 years had an elevated 80% risk of DES compared with the non-FM group. Without comorbidities, FM patients had an approximately 1.40-fold risk of DES than those without FM. The additive effects of FM and IBS or FM and sleep disturbance were pointed out that the risk for DES would be elevated when the FM patients with IBS or sleep disturbance. FM patients have a higher incidence of DES than that of non-FM patients. They carry long-term DES risks from a relatively young age, particularly those with psychiatric problems. Risk stratification for a timely psychiatric medication intervention and risk modifications are not intended. PMID- 26825914 TI - Combination of Cisplatin, Ifosfamide, and Adriamycin as Neoadjuvant Chemotherapy for Extremity Soft Tissue Sarcoma: A Report of Twenty-Eight Patients. AB - To investigate the clinical efficacy of neoadjuvant chemotherapy in the treatment of extremity soft tissue sarcomas (STSs). We retrospectively analyzed 28 patients with extremity STS that received 2 cycles of preoperative and 6 cycles of postoperative neoadjuvant chemotherapy between May 2009 and June 2012. Chemotherapy comprised intravenous cisplatin (DDP) (120 mg/m(2), for 1 day), followed 1 week later with 5 days 2 g/m(2) ifosfamide (IFO) and 3 days 30 mg/m(2) adriamycin (ADM). CT scans of the lungs and X-ray films of the lesion sites were reviewed. Eighteen patients were treated for primary tumor and 10 for tumor recurrence. Overall tumor diameter ranged from 8 to 30 cm based on body surface measurement. A total of 224 cycles of chemotherapy were carried out and patients were followed up for 12 to 59 months. Twenty-five patients underwent wide resection surgery (89.2%), and 3 underwent amputation (10.7%). Disease-free survival was realized in 20 patients and 3 patients survived with tumors. Two year disease-free survival rate was 71.4%, and overall 2-year survival rate was 82.1%. Postoperative metastases were observed in 5 patients, and all died of lung metastases. Postoperative recurrence was observed in 4 patients (including 1 patient occurred metastases later). Tumor size was reduced by 30% +/- 11.3% on average after the preoperative chemotherapy, and was reduced by 43% +/- 7.8% in 22 patients with tumors >15 cm in the diameter. Twelve patients achieved partial remission, 14 stable disease and 2 experienced progressive disease. Objective response rate was 42.9%. Disease control rate was 92.9%. Chemotherapy was well tolerated in all the patients. Main adverse reactions were transient and resolved after chemotherapy. Neoadjuvant chemotherapy is effective in the treatment of extremity STS. PMID- 26825915 TI - Dynamics of Genotypic Mutations of the Hepatitis B Virus Associated With Long Term Entecavir Treatment Determined With Ultradeep Pyrosequencing: A Retrospective Observational Study. AB - The aim of the study is to explore the evolution of genotypic mutations within the reverse transcriptase region in partial virological responders (PVRs) receiving long-term entecavir (ETV) treatment. A total of 32 patients were classified as completely virological responders (CVRs) (n = 12) or PVRs (n = 20). Five partial responders were hepatitis B virus (HBV)-DNA positive after long-term therapy, which lasted for >3 years. A total of 71 serum samples from these 32 patients were assayed by ultra-deep pyrosequencing (UDPS): 32 samples were from all patients at baseline, and 39 were from PVRs with sequential inter-treatment. Approximately 84,708 sequences were generated per sample. At baseline, the quasispecies heterogeneity did not significantly differ between the 2 groups. The frequencies of substitutions indicating pre-existence of nucleos(t)ide analog resistant (NAr) mutants ranged from 0.10% to 6.70%, which did not statistically differ between groups either. However, the substitutions associated with the NAr mutants were significantly different from those associated with the non-NAr mutants in 13 patients; 6 of these patients were PVRs and the others were CVRs. Five patients were HBV DNA positive after regular ETV monotherapy for >3 years, and 4 of these patients underwent mild NAr substitution fluctuations (<20%). One patient developed virological breakthrough while bearing single, double, and triple (rtL180 M, rtM204 V, rtS202G) substitutions. In addition to the common substitutions, unknown amino acid substitutions, such as rtL145 M/S, rtF151Y/L, rtR153Q, rtI224 V, rtN248H, rtS223A, rtS256C, need to be further verified. NAr substitutions are observed at frequencies of 0.10% to 6.7% before therapy. Long term ETV therapy generally results in virological responses, as long as the proportion of resistance mutations remains at a relatively low level. Genotypic resistance to ETV is detected in all PVRs receiving long-term ETV therapy. PMID- 26825916 TI - Acute Effects of Kinesio Taping on Knee Extensor Peak Torque and Stretch Reflex in Healthy Adults. AB - Kinesio Tex tape (KT) is used to prevent and treat sports-related injuries and to enhance muscle performance. It has been proposed that the direction of taping may either facilitate or inhibit the muscle by having different effects on cutaneous receptors that modulate excitability of the motor neurons. This study had 2 goals. First, we wished to determine if KT application affects muscle performance and if the method of application facilitates or inhibits muscle performance. This was assessed by measuring isokinetic knee extension peak torque in the knee extensor. Second, we assessed neurological effects of taping on the excitability of the motor neurons by measuring the reflex latency and action potential by electromyography (EMG) in the patellar reflex. The study was a single-blind, placebo-controlled crossover trial with 28 healthy volunteers with no history of knee injuries. Participants received facilitative KT treatment, inhibitory KT treatment, or Hypafix taping of the knee extensor. There were significant differences in the peak torque between 3 treatments (F(2,54) = 4.873, P < 0.01). Post hoc analysis revealed that facilitative KT treatment resulted in higher knee extensor peak torque performance than inhibitory KT treatment (P = 0.036, effect size 0.26). There were, however, no significant differences in the reflex latency (F(2,54) = 2.84, P = 0.067) nor in the EMG values (F(2,54) = 0.18, P = 0.837) in the patellar reflex between the 3 taping applications. The findings suggest that the direction of KT application over the muscle has specific effects on muscle performance. Given the magnitude of effect is small, interpretation of clinical significance should be considered with caution. The underlying mechanism warrants further investigation. PMID- 26825917 TI - MIF Gene Polymorphism rs755622 Is Associated With Coronary Artery Disease and Severity of Coronary Lesions in a Chinese Kazakh Population: A Case-Control Study. AB - Inflammation plays an important role in the pathogenesis of atherosclerosis. Recent studies indicate that macrophage migration inhibitory factor (MIF) is a potent proinflammatory cytokine which mediates the inflammatory process during atherosclerosis. The polymorphism of MIF gene (rs755622 [-173G/C], rs1007888, and rs2096525) were genotyped by TaqMan single nucleotide polymorphism (SNP) genotyping assay in 320 patients with coronary artery disease (CAD) and 603 controls in a Chinese Kazakh population. Coronary angiography was performed on all CAD patients and Gensini score was used to assess the severity of coronary artery lesions. The frequency of the CC genotype and C allele of rs755622 were significantly higher in CAD patients than that in control subjects (8.4% vs. 5.1%, P < 0.001, 30.3% vs. 22.1%, P < 0.001, respectively). Multivariate logistic regression analysis showed that individuals with CC genotype or C allele had a higher risk for CAD (CC genotype vs. GG genotype, OR = 2.224, 95% CI, 1.239 3.992, P = 0.007, and C allele vs. G allele, OR = 1.473, 95% CI, 1.156-1.876, P = 0.002, respectively). Moreover, CAD patients with rs755622 C allele (CC + CG genotype) have higher levels of Gensini score when compared to C allele noncarriers (32.74 +/- 26.66 vs. 21.44 +/- 19.40, P < 0.001, adjusted). Our results suggested that the CC genotype and C allele of MIF rs755622 SNP may be a genetic marker for the risk of CAD and potentially predict the severity of CAD in Chinese Kazakh population. PMID- 26825918 TI - Combined Association of Vitamin D and Sex Hormone Binding Globulin With Nonalcoholic Fatty Liver Disease in Men and Postmenopausal Women: A Cross Sectional Study. AB - This study aimed to explore the combined associations of 25(OH)-vitamin D and sex hormone binding globulin (SHBG) with nonalcoholic fatty liver disease (NAFLD) in men and postmenopausal women. Our data, which were based on the population, were collected from 16 sites in East China in 2014. There were 2700 men with a mean age of 53 years and 1461 women over 55 who were considered postmenopausal enrolled in the study. Levels of 25(OH)D and SHBG were measured using chemiluminescence assay. NAFLD was measured using liver ultrasound. Multivariable adjusted logistic regression models examined associations of 25(OH)D and SHBG tertiles with odds of mild and moderate-severe NAFLD. Both the low 25(OH)D and low SHBG groups were significantly associated with higher odds of mild NAFLD (men: OR 1.37, 95% CI 1.05, 1.78 in low 25(OH)D group; OR 1.73, 95% CI 1.23, 2.45 in low SHBG group; women: OR 1.51, 95% CI 1.08, 2.12 in low 25(OH)D group; OR 2.16, 95% CI 1.48, 3.14 in low SHBG group) and moderate-severe NAFLD (men: OR 1.61, 95% CI 1.24, 2.10 in low 25(OH)D group; OR 3.42, 95% CI 2.41, 4.87 in low SHBG group; women: OR 1.66, 95% CI 1.14, 2.42 in low 25(OH)D group; OR 6.84, 95% CI 4.31, 10.84 in low SHBG group). However, the combined association of low 25(OH)D and low SHBG was much larger, especially in moderate-severe NAFLD (men: OR 6.57, 95% CI 3.87, 11.18; women: OR 8.16, 95% CI 3.98, 16.73). The associations were independent of age, total testosterone, abdominal obesity, diabetes, and lipid profile. The negative associations of 25(OH)D and SHBG levels with NAFLD are strongest when viewed in combination in men and postmenopausal women. Further studies should determine the cause-effect relationship and investigate the underlying mechanisms of this finding. PMID- 26825919 TI - New-onset Atrial Fibrillation is Associated With Polycystic Kidney Disease: A Nationwide Population-based Cohort Study. AB - Cardiovascular complications remain the major problems contributing to morbidity and mortality in patients with polycystic kidney disease (PKD). Therefore, the authors hypothesized that atrial fibrillation (AF) is closely associated with PKD. The authors conducted a nationwide population-based cohort study to investigate the risk of AF in patients with PKD. Using data from inpatient claims, the authors enrolled 7203 patients aged over 20 years who were diagnosed with PKD from 1998 to 2010 with no history of AF as the PKD cohort. They randomly selected 28,739 people without PKD as controls and frequency matched them with patients with PKD according to their age, sex, and baseline comorbidity. In total, 247 PKD patients were diagnosed with AF, representing an incidence of 7.08 per 1000 person-years, whereas 807 cases of AF occurred in the comparison cohort, yielding an incidence of 4.98 per 1000 person-y, with an adjusted HR (aHR) of 1.31 (95% CI = 1.14-1.51). The risk of AF increased from an aHR of 1.59 (95% CI = 1.15-2.21) to 3.64 (95% CI = 1.93-6.85) when the number of risk factors increased from 1 to more than 5 in comparison with patients without risk factors. A remarkably high incidence rate and risk was observed in patients with PKD when multiple risk factors were combined. A high index of suspicion should be maintained when examining PKD patients with irregular betas. Early prophylactic therapy is warranted in these patients. PMID- 26825920 TI - Preoperative Plasma Fibrinogen Level as a Significant Prognostic Factor in Patients With Localized Renal Cell Carcinoma After Surgical Treatment. AB - We sought to investigate the association of preoperative fibrinogen levels with clinicopathologic outcomes after surgical treatment of nonmetastatic renal cell carcinoma. We reviewed the records of 1511 patients who had their fibrinogen levels measured preceding surgery. The associations between preoperative fibrinogen level and risk of adverse clinicopathologic outcomes were tested using the multivariate logistic regression and multiple Cox-proportional hazards model, respectively. Based on plasma fibrinogen levels, we stratified the patients into 2 groups with a cut-off value of 328 mg/dL. Kaplan-Meier analysis showed significantly inferior survival outcomes in progression-free (P < 0.001), cancer specific (P < 0.001), and overall survival (P < 0.001). In multivariate analyses, a high fibrinogen level (>=328 mg/dL) was significantly related to a higher Fuhrman grade (hazard ratio [HR] 1.374, P = 0.006) and a larger tumor size (>=7 cm) (HR 2.364, P < 0.001). Multivariate Cox analysis also revealed that a high preoperative fibrinogen level is a significant predictor for poor disease progression (HR 1.857, P < 0.001), cancer-specific survival (HR 3.608, P = 0.003), and overall survival (HR 1.647, P = 0.027). Increased plasma fibrinogen levels were significantly associated with poor pathological features and worse survival outcomes in patients with nonmetastatic renal cell carcinoma after surgical treatment. Further evaluations such as prospective randomized trials are needed to understand the underlying mechanism for these associations. PMID- 26825921 TI - Bulbar Paralysis and Facial Paralysis due to Metastatic Hepatocellular Carcinoma: A Case Report and Literature Review. AB - Skull-base metastasis (SBM) from hepatocellular carcinoma (HCC) is extremely rare, and multiple cranial nerve paralysis due to SBM from HCC is also rare. We report a case of bulbar and facial paralysis due to SBM from HCC. A 46-year-old Chinese man presented with a hepatic right lobe lesion that was detected during a routine physical examination. After several failed attempts to treat the primary tumor and bone metastases, neurological examination revealed left VII, IX, X, and XI cranial nerve paralysis. Computed tomography of the skull base subsequently revealed a large mass that had destroyed the left occipital and temporal bones and invaded the adjacent structure. After radiotherapy (27 Gy, 9 fractions), the patient experienced relief from his pain, and the cranial nerve dysfunction regressed. However, the patient ultimately died, due to the tumor's progression. Radiotherapy is usually the best option to relieve pain and achieve regression of cranial nerve dysfunction in cases of SBM from HCC, although early treatment is needed to achieve optimal outcomes. The present case helps expand our understanding regarding this rare metastatic pathway and indicates that improved awareness of SBM in clinical practice can help facilitate timely and appropriate treatment. PMID- 26825922 TI - Long-Term Follow-Up Results From PET/CT Surveillance After Surgical Resection of Lung Adenocarcinoma Manifesting as Ground-Glass Opacity. AB - The purpose of our study was to retrospectively evaluate the value of F fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for postoperative surveillance of lung adenocarcinoma manifesting as ground-glass opacity (GGO).From May 2003 to December 2007, 111 patients with surgically resected lung adenocarcinoma manifesting as GGO were included. Clinical findings of recurrence and survival, CT features, and maximum standardized uptake value (SUVmax) were reviewed and compared among 3 groups according to GGO proportion: Group I, GGO 100%; Group II, GGO >=50%; Group III, GGO < 50%. Disease-free survival (DFS) was estimated using the Kaplan-Meier method. Diagnostic performances of CT and PET/CT for recurrence were compared during a long-term follow-up period of >5 years.Recurrence was identified in Group III (18 of 53, 34%) but not in Groups I (n = 25) or II (n = 33) over a mean follow-up period of 74 months. Group showed significant differences in GGO proportion, SUVmax, and DFS duration (P < 0.001). PET/CT led to 6 false-positive and 5 false-negative interpretations of recurrence. For surveillance CT, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 94.4%, 98.6%, 98.2%, 94.4%, and 98.9%, respectively; for PET/CT, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 72.2%, 92.3%, 88.5%, 68.4%, and 93.5%, respectively. CT showed significantly higher accuracy than PET/CT (P = 0.0188).FDG-PET/CT showed no clear advantage for postoperative surveillance of lung cancer with predominant GGO because of low incidence of recurrence and frequent false-positive and false-negative results. PMID- 26825923 TI - Early interruption of exclusive breastfeeding: results from the eight-country MAL ED study. AB - We report the infant feeding experiences in the first month of life for 2,053 infants participating in "Malnutrition and Enteric Infections: Consequences for Child Health and Development" (MAL-ED). Eight sites (in Bangladesh, India, Nepal, Pakistan, Brazil, Peru, South Africa, Tanzania), each followed a cohort of children from birth (by day 17), collecting detailed information on infant feeding practices, diet and illness episodes. Mothers were queried twice weekly regarding health status, breastfeeding and the introduction (or no) of non-breast milk liquids and foods. Here, our goal is to describe the early infant feeding practices in the cohort and evaluate factors associated with termination of exclusive breastfeeding in the first month of life. With data from enrollment to a visit at 28-33 days of life, we characterized exclusive, predominant or partial breastfeeding (using a median of 6-9 visits per child across the sites). Only 6 of 2,053 infants were never breastfed. By one month, the prevalences of exclusive breastfeeding were < 60% in 6 of 8 sites, and of partial breastfeeding (or no) were > 20% in 6 of 8 sites. Logistic regression revealed that prelacteal feeding (given to 4-63% of infants) increased the likelihood of partial breastfeeding (Odds Ratio (OR): 1.48 (95% confidence interval (CI): 1.04, 2.10), as did the withholding of colostrum (2-16% of infants) (OR: 1.63:1.01, 2.62), and being a first-time mother (OR: 1.38:1.10, 1.75). Our results reveal diversity across these sites, but an overall trend of early transition away from exclusive breastfeeding in the first month of life. Interventions which introduce or reinforce the WHO/UNICEF Ten Steps for Successful Breastfeeding are needed in these sites to improve breastfeeding initiation, to reinforce exclusive breastfeeding and delay introduction of non-breast milk foods and/or liquids. PMID- 26825924 TI - Jump, Hop, or Skip: Modeling Practice Effects in Studies of Determinants of Cognitive Change in Older Adults. AB - Improvements in cognitive test scores upon repeated assessment due to practice effects (PEs) are well documented, but there is no empirical evidence on whether alternative specifications of PEs result in different estimated associations between exposure and rate of cognitive change. If alternative PE specifications produce different estimates of association between an exposure and rate of cognitive change, this would be a challenge for nearly all longitudinal research on determinants of cognitive aging. Using data from 3 cohort studies-the Three City Study-Dijon (Dijon, France, 1999-2010), the Normative Aging Study (Greater Boston, Massachusetts, 1993-2007), and the Washington Heights-Inwood Community Aging Project (New York, New York, 1999-2012)-for 2 exposures (diabetes and depression) and 3 cognitive outcomes, we compared results from longitudinal models using alternative PE specifications: no PEs; use of an indicator for the first cognitive visit; number of prior testing occasions; and square root of the number of prior testing occasions. Alternative specifications led to large differences in the estimated rates of cognitive change but minimal differences in estimated associations of exposure with cognitive level or change. Based on model fit, using an indicator for the first visit was often (but not always) the preferred model. PE specification can lead to substantial differences in estimated rates of cognitive change, but in these diverse examples and study samples it did not substantively affect estimated associations of risk factors with change. PMID- 26825926 TI - Physical Trauma and Amyotrophic Lateral Sclerosis: A Population-Based Study Using Danish National Registries. AB - Prior studies have suggested that physical trauma might be associated with the development of amyotrophic lateral sclerosis (ALS). We conducted a population based, individually matched case-control study in Denmark to assess whether hospitalization for trauma is associated with a higher risk of developing ALS. There were 3,650 incident cases of ALS in the Danish National Patient Register from 1982 to 2009. We used risk-set sampling to match each case to 100 age- and sex-matched population controls alive on the date of the case's diagnosis. Odds ratios and 95% confidence intervals were calculated using a conditional logistic regression model. History of trauma diagnosis was also obtained from the Danish Patient Register. When traumas in the 5 years prior to the index date were excluded, there was a borderline association between any trauma and ALS (odds ratio (OR) = 1.09, 95% confidence interval (CI): 0.99, 1.19). A first trauma before age 55 years was associated with ALS (OR = 1.22, 95% CI: 1.08, 1.37), whereas first traumas at older ages were not (OR = 0.97, 95% CI: 0.85, 1.10). Our data suggest that physical trauma at earlier ages is associated with ALS risk. Age at first trauma could help explain discrepancies in results of past studies of trauma and ALS. PMID- 26825927 TI - Natural History of Dependency in the Elderly: A 24-Year Population-Based Study Using a Longitudinal Item Response Theory Model. AB - We aimed to describe the hierarchical structure of Instrumental Activities of Daily Living (IADL) and basic Activities of Daily Living (ADL) and trajectories of dependency before death in an elderly population using item response theory methodology. Data were obtained from a population-based French cohort study, the Personnes Agees QUID (PAQUID) Study, of persons aged >=65 years at baseline in 1988 who were recruited from 75 randomly selected areas in Gironde and Dordogne. We evaluated IADL and ADL data collected at home every 2-3 years over a 24-year period (1988-2012) for 3,238 deceased participants (43.9% men). We used a longitudinal item response theory model to investigate the item sequence of 11 IADL and ADL combined into a single scale and functional trajectories adjusted for education, sex, and age at death. The findings confirmed the earliest losses in IADL (shopping, transporting, finances) at the partial limitation level, and then an overlapping of concomitant IADL and ADL, with bathing and dressing being the earliest ADL losses, and finally total losses for toileting, continence, eating, and transferring. Functional trajectories were sex-specific, with a benefit of high education that persisted until death in men but was only transient in women. An in-depth understanding of this sequence provides an early warning of functional decline for better adaptation of medical and social care in the elderly. PMID- 26825925 TI - Pregnancy as a Window to Future Cardiovascular Health: Design and Implementation of the nuMoM2b Heart Health Study. AB - The National Institute of Child Health and Human Development's Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be (nuMoM2b) Heart Health Study (HHS) was designed to investigate the relationships between adverse pregnancy outcomes and modifiable risk factors for cardiovascular disease. The ongoing nuMoM2b-HHS, which started in 2013, is a prospective follow-up of the nuMoM2b cohort, which included 10,038 women recruited between 2010 and 2013 from 8 centers across the United States who were initially observed over the course of their first pregnancies. In this report, we detail the design and study procedures of the nuMoM2b-HHS. Women in the pregnancy cohort who consented to be contacted for participation in future studies were approached at 6-month intervals to ascertain health information and to maintain ongoing contact. Two to 5 years after completion of the pregnancy documented in the nuMoM2b, women in the nuMoM2b-HHS were invited to an in-person study visit. During this visit, they completed psychosocial and medical history questionnaires and had clinical measurements and biological specimens obtained. A subcohort of participants who had objective assessments of sleep-disordered breathing during pregnancy were asked to repeat this investigation. This unique prospective observational study includes a large, geographically and ethnically diverse cohort, rich depth of phenotypic information about adverse pregnancy outcomes, and clinical data and biospecimens from early in the index pregnancy onward. Data obtained from this cohort will provide mechanistic and clinical insights into how data on a first pregnancy can provide information about the potential development of subsequent risk factors for cardiovascular disease. PMID- 26825928 TI - An Autoimmune Basis for Diabetes-Related Chorea? PMID- 26825929 TI - IVF affects embryonic development in a sex-biased manner in mice. AB - Increasing evidence indicates that IVF (IVF includes in vitro fertilization and culture) embryos and babies are associated with a series of health complications, and some of them show sex-dimorphic patterns. Therefore, we hypothesized that IVF procedures have sex-biased or even sex-specific effects on embryonic and fetal development. Here, we demonstrate that IVF-induced side effects show significant sexual dimorphic patterns from the pre-implantation to the prenatal stage. During the pre-implantation stage, female IVF embryos appear to be more vulnerable to IVF-induced effects, including an increased percentage of apoptosis (7.22 +/- 1.94 vs 0.71 +/- 0.76, P<0.01), and dysregulated expression of representative sex dimorphic genes (Xist, Hprt, Pgk1 and Hsp70). During the mid-gestation stage, IVF males had a higher survival rate than IVF females at E13.5 (male:female=1.33:1), accompanied with a female-biased pregnancy loss. In addition, while both IVF males and females had reduced placental vasculogenesis/angiogenesis, the compensatory placental overgrowth was more evident in IVF males. During the late gestation period, IVF fetuses had a higher sex ratio (male:female=1.48:1) at E19.5, and both male and female IVF placentas showed overgrowth. After birth, IVF males grew faster than their in vivo (IVO) counterparts, while IVF females showed a similar growth pattern with IVO females. The present study provides a new insight into understanding IVF-induced health complications during embryonic and fetal development. By understanding and minimizing these sex-biased effects of the IVF process, the health of IVF-conceived babies may be improved in the future. PMID- 26825930 TI - Chromosomal analysis of blastocysts from balanced chromosomal rearrangement carriers. AB - Balanced chromosomal rearrangements (CRs) are among the most common genetic abnormalities in humans. In the present study, we have investigated the degree of consistency between the chromosomal composition of the blastocyst inner cell mass (ICM) and trophectoderm (TE) in carriers with balanced CR, which has not been previously addressed. As a secondary aim, we have also evaluated the validity of cleavage-stage preimplantation genetic diagnosis (PGD) based on fluorescence in situ hybridization (FISH) of blastocysts from CR carriers. Blastocyst ICM and TE were screened for chromosomal aneuploidy and imbalance of CR-associated chromosomes based on whole-genome copy number variation analysis by low-coverage next-generation sequencing (NGS) following single-cell whole-genome amplification by multiple annealing and looping-based amplification cycling. The NGS results were analyzed without knowledge of cleavage-stage FISH results. NGS results for blastocyst ICM and TE from CR carriers were 86.49% (32/37) consistent. Of the 1702 (37 * 46) chromosomes examined, 99.47% (1693/1702) showed consistency. However, only 40.0% (18/45) of all embryos had consistent results for chromosomes involved in CR, as determined by blastocyst NGS and cleavage-stage FISH. Of the 85 CR-affected chromosomes analyzed by FISH, 37.65% (32/85) were incongruous with NGS results, with 87.5% (28/32) showing imbalanced composition by FISH but balanced composition by NGS. These results indicate that chromosomal composition of blastocyst ICM and TE in balanced CR carriers is highly consistent, and that PGD based on cleavage-stage FISH is inaccurate; therefore, using blastocyst TE biopsies for NGS-based PGD is recommended for identifying chromosomal imbalance in embryos from balanced CR carriers. PMID- 26825931 TI - The prognostic value of neutrophil-to-lymphocyte ratio on mortality in critically ill trauma patients. AB - BACKGROUND: Recent studies suggest that the neutrophil-lymphocyte ratio (NLR) as a marker of inflammation is associated with mortality in surgical patients. The aim of this study was to determine the prognostic impact of NLR in critically ill trauma patients. METHODS: This is a retrospective cohort study involving all trauma patients 16 years or older admitted to the surgical intensive care unit of a Level 1 trauma center (January 2013 to January 2014). The predictive capacity of NLR on mortality was assessed using a receiver operating characteristic curve analysis. To identify the effect of the NLR on survival, a separate log-rank test was used. Multivariable Cox proportional hazard modeling was used to identify independent predictors of mortality. RESULTS: During the study period, 1,356 patients met inclusion criteria. Of these, 74% were male, 86% sustained blunt trauma, and the median age was 49 years (interquartile range [IQR], 35). The median Glasgow Coma Scale (GCS) score and Injury Severity Score (ISS) were 15 (IQR, 3) and 13 (IQR, 14), respectively. With the use of the receiver operating characteristic curve analyses at intensive care unit Days 2 and 5, optimal NLR cutoff values of 8.19 and 7.92 were calculated by maximizing the Youden index. Kaplan-Meier curves revealed an NLR greater than or equal to these cutoff values as a marker for increased in-hospital mortality (p < 0.001, log-rank test). The Cox regression model demonstrated that an NLR greater than 8.19 and 7.92 are independently associated with in-hospital mortality at Days 2 and 5, respectively (hazard ratio, 1.602 [p = 0.019] and 3.758 [p < 0.001]). CONCLUSION: NLR is associated with mortality in critically ill trauma patients. Prospective validation of its role as a predictive marker for outcomes is warranted. LEVEL OF EVIDENCE: Prognostic study, level III. PMID- 26825932 TI - A retrospective analysis of the etiologic agents and antibiotic susceptibility pattern of uropathogens isolated in the Jigme Dorji Wangchuck National Referral Hospital, Thimphu, Bhutan. AB - BACKGROUND: Urinary tract infection is one of the major public health problems. Specific population studies to understand the common etiologic agents and antibiotic susceptibility patterns are important to determine the empirical treatment of urinary tract infections. This is the first study in Bhutan to analyze the etiologic agents and antibiotic susceptibility pattern of uropathogens isolated from patients visiting Jigme Dorji Wangchuck National Referral Hospital with the ultimate goal of guiding empirical treatment. METHODS: Hospital based (inpatients/outpatients) retrospective cross sectional study of 6030 clinically suspected patients with urinary tract infections who have submitted urine samples for culture in a 6 months period was done. Urine samples were collected and processed as per standard microbiological procedures and antibiotic susceptibility testing performed by CLSI guidelines. RESULTS: Significant bacteriuria were detected in 14.9 % of the total patients. The most common uropathogens isolated were Escherichia coli (79.3 %) followed by Klebsiella pneumoniae. Females around the age group of 18-26 have the highest prevalence of urinary tract infection. The highest rate of antibiotic resistance was seen in amoxicillin (71.4 %) and nalidixic acid (80.3 %), and resistance were lower in nitrofuration (3.4 %) and gentamycin (17.5 %). The third generation cephalosporin resistance (which is a surrogate marker of ESBL) was 16.1 % in outpatient and 16.7 % approximately in inpatient setting. CONCLUSION: Escherichia coli was the predominant uropathogen making up 79.3 % (outpatient 81.1 % and inpatient 69.5 %) of the total and its antibiotic susceptibility pattern needs to be considered for treating community-acquired UTIs empirically. The third generation cephalosporin resistance (which is a surrogate marker of ESBL) is alarmingly high among the isolates and there is need for further studies. PMID- 26825933 TI - Bronchiolitis obliterans organising pneumonia associated with anticonvulsant hypersensitivity syndrome induced by lamotrigine. AB - A 14-year-old girl who was known to have a seizure disorder and on lamotrigine treatment was admitted to the hospital, with a history of rash, fever and cough. Her condition deteriorated with clinical features suggestive of anticonvulsant hypersensitivity syndrome (ACHS) complicated with bronchiolitis obliterans organising pneumonia (BOOP). Her chest CT showed multifocal parenchymal opacities and lung biopsy was typical for BOOP. Initially, the lamotrigine was discontinued since the onset of the rash, then she was treated for pneumonia with antibiotics, which may have delayed the diagnosis. Eventually, BOOP was considered and she was treated with a high dose of corticosteroid. She improved clinically and her repeated chest CT showed a marked resolution of the lesions. This case illustrates the possible occurrence of BOOP as a complication of ACHS secondary to lamotrigine treatment. PMID- 26825934 TI - Successful pregnancy with autoimmune cirrhosis. AB - Pregnancy with liver cirrhosis is a rare and dangerous event that exposes mother and fetus to potentially lethal risks. During pregnancy, hepatic decompensation could suffice and the development of hepatic failure and encephalopathy could occur. The incidence of obstetric complications is also increased with a high rate of pre-eclampsia, postpartum bleeding, preterm delivery and stillbirth. We report a case of a 27-year-old woman with autoimmune hepatitis and liver cirrhosis complicated by splenomegaly, oesophageal varices and severe thrombocytopaenia. During pregnancy, close clinical and analytical surveillance was performed. She was medicated with corticosteroids, azathioprine and propranolol. At the 25th week of gestation, an upper gastrointestinal endoscopy was performed to control oesophageal varices. This patient had an uneventful pregnancy until 37 weeks. At 37th week of gestation, after spontaneous rupture of membranes, signs of acute fetal distress were observed, and an urgent caesarean was performed. Good neonatal and maternal outcomes were achieved. PMID- 26825935 TI - Rare gynaecological emergency: massive intraperitoneal haemorrhage from spontaneous rupture of a superficial vessel on a large leiomyoma. AB - Uterine leiomyomas rarely present as gynaecological emergencies. We report a case of a 29-year-old nulliparous woman, with a negative pregnancy test, who presented with collapse and an admission haemoglobin count of 68 g/L. Urgent CT of the abdomen revealed a 14 * 19 * 10 cm uterine fibroid and intraperitoneal free fluid. Emergency laparotomy confirmed massive intraperitoneal haemorrhage from a large serosal vessel on top of a 19 cm subserosal fibroid. A myomectomy was performed, preserving this patient's fertility. Histopathology confirmed a benign leiomyoma with hydropic changes. PMID- 26825936 TI - Lipoprotein lipase deficiency presenting with neonatal perianal abscesses. AB - Lipoprotein lipase (LPL), a member of the triglyceride lipase gene family, is synthesised by parenchymal cells of the heart, skeletal muscle and adipose tissues before being transported to luminal surfaces of vascular endothelial cells to exert its main physiological function to hydrolyse plasma lipoproteins. LPL deficiency is a rare autosomal recessive disorder, resulting in severe hypertriglyceridaemia from birth. The effect of marked hypertriglyceridaemia on the immune function in children has not been described. We present a case of a neonate with LPL deficiency and grossly elevated plasma triglyceride levels, presenting with recurrent and recalcitrant perianal abscesses suggestive of underlying immunodeficiency. With reduced levels of plasma triglycerides, the recurrent perianal infections resolved. This case report reviews evidence for potential deleterious effects of hypertriglyceridaemia on immune function, however, underlying mechanisms are poorly understood. Whether hypertriglyceridaemia contributes to immune dysfunction in this context is unknown. If there is a pathophysiological link, this may have implications for hypertriglyceridaemia management. PMID- 26825937 TI - Ureteric lymphoma as a rare cause of right lower ureteric obstruction. AB - Primary lymphoid neoplasms of the urinary tract are exceedingly rare, with only 21 cases being reported and comprising less than 5% of all primary extranodal lymphomas. We report a case of a 45-year-old man who presented with right flank pain and weight loss, and who was found to have a stricture in the right lower ureter causing ureteral obstruction. Histopathology revealed lower ureteric non Hodgkin lymphoma, which, on further evaluation, was found to be isolated ureteric lymphoma. The patient was doing well after six cycles of R-CHOP chemotherapy. This case is being reported as a rare cause of distal ureteric obstruction. PMID- 26825938 TI - Kleptomania following hypoxic-ischaemic damage to bilateral caudate nuclei. PMID- 26825939 TI - Unusual large functional adrenocortical carcinoma in a young woman. PMID- 26825940 TI - Laryngopyocoele: an unusual cause of airway obstruction. PMID- 26825941 TI - The Role of Individual and Collective Mindfulness in Promoting Occupational Safety in Health Care. AB - Although the importance of safety regulations is highly emphasized in hospitals, nurses frequently work around, or intentionally bypass, safety regulations. We argue that work-arounds occur because adhering to safety regulations usually requires more time and work process design often lacks complementarity with safety regulations. Our main proposition is that mindfulness is associated with a decrease in occupational safety failures through a decrease in work-arounds. First, we propose that individual mindfulness may prevent the depletion of motivational resources caused by worrying about the consequences of time lost when adhering to safety regulations. Second, we argue that collective mindfulness may provide nursing teams with a cognitive infrastructure that facilitates the detection and adaptation of work processes. The results of a multilevel analysis of 580 survey responses from nurses are consistent with our propositions. Our multilevel analytic approach enables us to account for the unique variance in work-arounds that individual and collective mindfulness explain. PMID- 26825942 TI - Antitrust and Accountable Care Organizations: Observations for the Physician Market. AB - The creation of Accountable Care Organizations (ACOs) under the Medicare Shared Savings Program has generated antitrust concerns. Utilizing a framework developed by the antitrust authorities for analyzing provider concentration for potential ACO participants, we examine the market for physician services, with a focus on the share of practices that could potentially be subject to antitrust scrutiny. Our findings suggest that while most physician practices would fall below the threshold that could raise anticompetitive concerns, this varies considerably by market and specialty. Furthermore, we find that the largest physician practice in most markets potentially remains at risk for antitrust review under the existing criteria. PMID- 26825943 TI - Nurse Practitioner Autonomy and Satisfaction in Rural Settings. AB - Rural primary care shortages may be alleviated if more nurse practitioners (NPs) practiced there. This study compares urban and rural primary care NPs (classified by practice location in urban, large rural, small rural, or isolated small rural areas) using descriptive analysis of the 2012 National Sample Survey of NPs. A higher share of rural NPs worked in states without physician oversight requirements, had a DEA (drug enforcement administration) number, hospital admitting privileges, and billed using their own provider identifier. Rural NPs more often reported they were fully using their NP skills, practicing to the fullest extent of the legal scope of practice, satisfied with their work, and planning to stay in their jobs. We found lower per capita NP supply in rural areas, but the proportion in primary care increased with rurality. To meet rural primary care needs, states should support rural NP practice, in concert with support for rural physician practice. PMID- 26825944 TI - Landscape changes have greater effects than climate changes on six insect pests in China. AB - In recent years, global changes are the major causes of frequent, widespread outbreaks of pests in mosaic landscapes, which have received substantial attention worldwide. We collected data on global changes (landscape and climate) and economic damage caused by six main insect pests during 1951-2010 in China. Landscape changes had significant effects on all six insect pests. Pest damage increased significantly with increasing arable land area in agricultural landscapes. However, climate changes had no effect on damage caused by pests, except for the rice leaf roller (Cnaphalocrocis medinalis Guenee) and armyworm (Mythimna separate (Walker)), which caused less damage to crops with increasing mean temperature. Our results indicate that there is slight evidence of possible offset effects of climate changes on the increasing damage from these two agricultural pests. Landscape changes have caused serious outbreaks of several species, which suggests the possibility of the use of landscape design for the control of pest populations through habitat rearrangement. Landscape manipulation may be used as a green method to achieve sustainable pest management with minimal use of insecticides and herbicides. PMID- 26825945 TI - Long noncoding RNAs as Organizers of Nuclear Architecture. AB - In the eukaryotic cell nucleus, chromatin and its associated macromolecules must be organized into a higher-ordered conformation to function normally. However, mechanisms underlying the organization and dynamics of the nucleus remain unclear. Long noncoding RNAs (lncRNAs), i.e., transcripts longer than 200 nucleotides with little or no protein-coding capacity, are increasingly recognized as important regulators in diverse biological processes. Recent studies have shown that some lncRNAs are involved in various aspects of genome organization, including the facilitation of chromosomal interactions and establishment of nuclear bodies, suggesting that lncRNAs act as general organizers of the nuclear architecture. Here, we discuss recent advances in this emerging and intriguing field. PMID- 26825946 TI - Histone modifications in DNA damage response. AB - DNA damage is a relatively common event in eukaryotic cell and may lead to genetic mutation and even cancer. DNA damage induces cellular responses that enable the cell either to repair the damaged DNA or cope with the damage in an appropriate way. Histone proteins are also the fundamental building blocks of eukaryotic chromatin besides DNA, and many types of post-translational modifications often occur on tails of histones. Although the function of these modifications has remained elusive, there is ever-growing studies suggest that histone modifications play vital roles in several chromatin-based processes, such as DNA damage response. In this review, we will discuss the main histone modifications, and their functions in DNA damage response. PMID- 26825947 TI - Emerging roles of non-coding RNAs in epigenetic regulation. AB - Recent deep sequencing surveys of mammalian genomes have unexpectedly revealed pervasive and complex transcription and identified tens of thousands of RNA transcripts that do not code for proteins. These non-coding RNAs (ncRNAs) highlight the central role of RNA in gene regulation. ncRNAs are arbitrarily divided into two main groups: The first includes small RNAs, such as miRNAs, piRNAs, and endogenous siRNAs, that usually range from 20 to 30 nt, while the second group includes long non-coding RNAs (lncRNAs), which are typically more than 200 nt in length. These ncRNAs were initially thought to merely regulate gene expression at the post-transcriptional level, but recent studies have indicated that ncRNAs, especially lncRNAs, are extensively associated with diverse chromatin remodeling complexes and target them to specific genomic loci to alter DNA methylation or histone status. These findings suggest an emerging theme of ncRNAs in epigenetic regulation. In this review, we discuss the wide spectrum of ncRNAs in the regulation of DNA methylation and chromatin state, as well as the key questions that needs to be investigated and acknowledging the elegant design of these intriguing macromolecules. PMID- 26825948 TI - Histone Variant H3.3: A versatile H3 variant in health and in disease. AB - Histones are the main protein components of eukaryotic chromatin. Histone variants and histone modifications modulate chromatin structure, ensuring the precise operation of cellular processes associated with genomic DNA. H3.3, an ancient and conserved H3 variant, differs from its canonical H3 counterpart by only five amino acids, yet it plays essential and specific roles in gene transcription, DNA repair and in maintaining genome integrity. Here, we review the most recent insights into the functions of histone H3.3, and the involvement of its mutant forms in human diseases. PMID- 26825949 TI - Single-base resolution analysis of DNA epigenome via high-throughput sequencing. AB - Epigenetic changes caused by DNA methylation and histone modifications play important roles in the regulation of various cellular processes and development. Recent discoveries of 5-methylcytosine (5mC) oxidation derivatives including 5 hydroxymethylcytosine (5hmC), 5-formylcytsine (5fC) and 5-carboxycytosine (5caC) in mammalian genome further expand our understanding of the epigenetic regulation. Analysis of DNA modification patterns relies increasingly on sequencing-based profiling methods. A number of different approaches have been established to map the DNA epigenomes with single-base resolution, as represented by the bisulfite-based methods, such as classical bisulfite sequencing (BS-seq), TAB-seq (TET-assisted bisulfite sequencing), oxBS-seq (oxidative bisulfite sequencing) and etc. These methods have been used to generate base-resolution maps of 5mC and its oxidation derivatives in genomic samples. The focus of this review will be to discuss the chemical methodologies that have been developed to detect the cytosine derivatives in the genomic DNA. PMID- 26825950 TI - Our paper 20 years later: the unfulfilled promises of nebulised adrenaline in acute severe asthma. PMID- 26825951 TI - Any trial can (almost) kill a good technique. PMID- 26825952 TI - Passive leg raising for predicting fluid responsiveness: a systematic review and meta-analysis. AB - PURPOSE: We performed a systematic review and meta-analysis of studies investigating the passive leg raising (PLR)-induced changes in cardiac output (CO) and in arterial pulse pressure (PP) as predictors of fluid responsiveness in adults. METHODS: MEDLINE, EMBASE and Cochrane Database were screened for relevant original and review articles. The meta-analysis determined the pooled area under the ROC curve, the sensitivity, specificity and threshold for the PLR test when assessed with CO and PP. RESULTS: Twenty-one studies (991 adult patients, 995 fluid challenges) were included. CO was measured by echocardiography in six studies, calibrated pulse contour analysis in six studies, bioreactance in four studies, oesophageal Doppler in three studies, transpulmonary thermodilution or pulmonary artery catheter in one study and suprasternal Doppler in one study. The pooled correlation between the PLR-induced and the fluid-induced changes in CO was 0.76 (0.73-0.80). For the PLR-induced changes in CO, the pooled sensitivity was 0.85 (0.81-0.88) and the pooled specificity was 0.91 (0.88-0.93). The area under the ROC curve was 0.95 +/- 0.01. The best threshold was a PLR-induced increase in CO >=10 +/- 2 %. For the PLR-induced changes in PP (8 studies, 432 fluid challenges), the pooled sensitivity was 0.56 (0.49-0.53), the pooled specificity was 0.83 (0.77-0.88) and the pooled area under the ROC curve was 0.77 +/- 0.05. Sensitivity and subgroup analysis were consistent with the primary analysis. CONCLUSIONS: PLR-induced changes in CO very reliably predict the response of CO to volume expansion in adults with acute circulatory failure. When PLR effects are assessed by changes in PP, the specificity of the PLR test remains acceptable but its sensitivity is poor. PMID- 26825954 TI - What's new in sepsis recognition in resource-limited settings? PMID- 26825953 TI - The ENCOURAGE mortality risk score and analysis of long-term outcomes after VA ECMO for acute myocardial infarction with cardiogenic shock. AB - PURPOSE: This study was designed to identify factors associated with in-intensive care unit (ICU) death and develop a practical mortality risk score for venoarterial-extracorporeal membrane oxygenation (VA-ECMO)-treated acute myocardial infarction (AMI) patients. Long-term survivors' health-related quality of life (HRQOL), anxiety, depression, and post-traumatic stress disorder (PTSD) frequencies were also assessed. METHODS: Data from 138 ECMO-treated AMI patients admitted to two French ICUs (2008-2013) were analyzed. ICU survivors contacted >6 months post-ICU discharge were assessed for HRQOL, psychological and PTSD status. RESULTS: Sixty-five patients (47%) survived to ICU discharge. On the basis of multivariable logistic regression analyses, the ENCOURAGE score was constructed with seven pre-ECMO parameters: age >60, female sex, body mass index >25 kg/m(2), Glasgow coma score <6, creatinine >150 MUmol/L, lactate (<2, 2-8, or >8 mmol/L), and prothrombin activity <50%. Six months after ECMO, probabilities of survival were 80, 58, 25, 20, and 7% for ENCOURAGE score classes 0-12, 13-18, 19-22, 23 27, and >=28, respectively. The ENCOURAGE score ROC AUC [0.84 (95% CI 0.77-0.91)] was significantly better than those of the SAVE, SAPS II, and SOFA scores. Survivors' HRQOL evaluated after median follow-up of 32 months revealed satisfactory mental health but persistent physical and emotional-related difficulties, with 34% (95% CI 20-49%) anxiety, 20% (95% CI 8-32%) depression, and 5% (95% CI 0-12%) PTSD symptoms reported. CONCLUSIONS: The ENCOURAGE score might be a useful tool to predict mortality of severe cardiogenic shock AMI patients who received VA-ECMO. However, it now needs prospective validation on other populations of AMI patients. PMID- 26825955 TI - Volume responsive, but does the patient need volume? PMID- 26825956 TI - Bronchoscopic balloon dilatation for tuberculosis-associated tracheal stenosis: a two case report and a literature review. AB - BACKGROUND: Bronchoscopic balloon dilatation (BBD) is a common strategy in the treatment of bronchostenosis. However, the longer dilating time in each inflation cycle (approximately 3-5 min) without mechanical ventilation is not possible for the treatment of tracheal stenosis. CASE PRESENTATION: In this study, we reported our experience of BBD with shorter dilating time (10 s or 1 min) and intermittent ventilation for the repair of tuberculous-associated tracheal stenosis in two cases of our hospital. After the surgeries, the physical examinations and pulmonary function were tested. In case 1, the cough and dyspnea syndromes subsided, wheeze and strid or in lungs were remarkably reduced, tracheal lumen was considerably expanded and pulmonary function was improved following the treatment. For the case 2, her chest tightness, shortness of breath symptoms were alleviated after the treatment. The middle and lower trachea stenosis was dilated and patent, but the right main bronchus stenosis was slightly improved. No restenosis occurred in the two patients in 1 year outpatient follow-up. CONCLUSIONS: These findings suggest that our modification in BBD is safe and effective for treating this patient with tracheal stenosis caused by tuberculosis, but the longer-term effect of the surgery in a large number of patients with longer follow-up remains to be seen. PMID- 26825957 TI - Embracing Comprehensive Mental Health and Social Services Programs to Serve Children Under California's Mental Health Services Act. AB - Authorized under California's Mental Health Services Act (MHSA) of 2004, full service partnership (FSP) programs address social welfare and other human service needs of seriously mentally ill adults and children who are especially socially and economically vulnerable or who are untreated or insufficiently treated. Because FSP enrollment should reflect greater individual and community distress, we investigated whether counties' enrollment of children into FSPs came from mental health system caseloads with higher crisis use, assessed trauma and substance abuse problems; and from counties which had more foster care placement, more child poverty, lower median household incomes and more unemployment. We addressed these questions in 36 counties over 34 quarters after MHSA's onset. Results indicated greater FSP enrollment for children was associated with higher county unemployment and foster care placement rates and with mental health systems which had increasing children's crisis rates over the study period. These findings suggest that underservice and community adversity prompt officials to adopt and make greater use of children's FSP programming, in keeping with MHSA's intensions. PMID- 26825958 TI - Autoinflation reduces middle ear effusion in children with otitis media with effusion. PMID- 26825959 TI - Gender ratio in a clinical population sample, age of diagnosis and duration of assessment in children and adults with autism spectrum disorder. AB - This article reports on gender ratio, age of diagnosis and the duration of assessment procedures in autism spectrum disorder diagnosis in a national study which included all types of clinical services for children and adults. Findings are reported from a retrospective case note analysis undertaken with a representative sample of 150 Scottish children and adults recently diagnosed with autism spectrum disorder. The study reports key findings that the gender ratio in this consecutively referred cohort is lower than anticipated in some age groups and reduces with increasing age. The gender ratio in children, together with the significant difference in the mean age of referral and diagnosis for girls compared to boys, adds evidence of delayed recognition of autism spectrum disorder in younger girls. There was no significant difference in duration of assessment for males and females suggesting that delays in diagnosis of females occur prior to referral for assessment. Implications for practice and research are considered. PMID- 26825960 TI - MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma. AB - Type 3 deiodinase (DIO3, D3) is reactivated in human neoplasias. Increased D3 levels in papillary thyroid carcinoma (PTC) have been associated with tumor size and metastatic disease. The objective of this study is to investigate the signaling pathways involved in DIO3 upregulation in PTC. Experiments were performed in human PTC cell lines (K1 and TPC-1 cells) or tumor samples. DIO3 mRNA and activity were evaluated by real-time PCR and ion-exchange column chromatography respectively. Western blot analysis was used to determine the levels of D3 protein. DIO3 gene silencing was performed via siRNA transfection. DIO3 mRNA levels and activity were readily detected in K1 (BRAF(V6) (0) (0E)) and, at lower levels, in TPC-1 (RET/PTC1) cells (P<0.007 and P=0.02 respectively). Similarly, DIO3 mRNA levels were higher in PTC samples harboring the BRAF(V600E) mutation as compared with those with RET/PTC1 rearrangement or negative for these mutations (P<0.001). Specific inhibition of BRAF oncogene (PLX4032, 3 MUM), MEK (U0126, 10-20 MUM) or p38 (SB203580, 10-20 MUM) signaling was associated with decreases in DIO3 expression in K1 and TPC-1 cells. Additionally, the blockage of the sonic hedgehog (SHH) pathway by cyclopamine (10 MUM) resulted in markedly decreases in DIO3 mRNA levels. Interestingly, siRNA mediated DIO3 silencing induced decreases on cyclin D1 expression and partial G1 phase cell cycle arrest, thereby downregulating cell proliferation. In conclusion, sustained activation of the MAPK and SHH pathways modulate the levels of DIO3 expression in PTC. Importantly, DIO3 silencing was associated with decreases in cell proliferation, thus suggesting a D3 role in tumor growth and aggressiveness. PMID- 26825961 TI - Rapid growth in early childhood associated with young adult overweight and obesity--evidence from a community based cohort study. AB - BACKGROUND: Rapid weight gain in early life may increase the risk of overweight and obesity in adulthood. We investigated the association between the rate of growth during early childhood and the development of overweight and obesity in young adults. METHODS: We used a prospective cohort study of 2077 young adults who were born between 1981 and 1984 in Brisbane, Australia and had anthropometry measurements available at birth, 6 months, 5 years, 14 years and 21 years of age. The associations of rate of early growth with body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) and their categories at 21 years were studied using multivariate analysis. RESULTS: We found that rapid weight gain [> + 0.67 standard deviation score (SDS)] in the first 5 years of life was associated with young adults' overweight status (BMI: adjusted OR = 2.35, 95% CI, 1.82-3.03; WC: adjusted OR = 2.20, 95% CI, 1.65-2.95). We also observed that slow weight gain in the first 5 years of age (< -0.67 SDS) was inversely associated with overweight (BMI: OR = 0.62, 95% CI, 0.45-0.84). Such associations were not found with WHR. Rapid weight gain in the first 6 months of life increased the risk of overweight as defined by BMI (adjusted OR = 1.13, 95% CI, 0.86-1.49) and WC (adjusted OR = 1.24, 95% CI, 0.92-1.67), but these associations were not statistically significant. CONCLUSION: Rapid weight gain in the first 5 years of life in children increased their risk of a higher BMI and WC in young adulthood, in contrast slow weight gain was inversely associated with weight status at 21 years. PMID- 26825962 TI - Widespread morbilliform rash due to sorafenib or vemurafenib treatment for advanced cancer; experience of a tertiary dermato-oncology clinic. AB - BACKGROUND: In the literature, there are minimal data for the treatment of grade 2 or 3 morbilliform/atypical target lesion rashes secondary to sorafenib or vemurafenib given for patients with advanced stage cancer. This poses a dilemma for clinicians, particularly in patients with advanced neoplastic disease for whom other optional treatments are limited. METHODS: The cohort included data on all patients attending the dermato-oncological clinic at a tertiary medical center that presented in 2011-2014 with a widespread rash following treatment with sorafenib or vemurafenib. All patients were prospectively followed. RESULTS: Eight patients met the study criteria. Five, under sorafenib, aged 50-65 years, presented with an extensive grade 2 (involving 20-30% of the body surface area, two patients) or grade 3 (three patients) morbilliform rash, 5-10 days after onset of the drug. Two had atypical target lesions. The dosage was temporarily reduced in only two patients, and oral steroids were added in four. Under vemurafenib, three patients presented with an extensive grade 3 morbilliform rash 5-10 days after onset of treatment. Two had atypical target lesions. The dose was temporarily reduced in one, and another patient stopped the drug at her own initiative; both also received steroids. The rash subsided after 2-3 weeks in all eight patients, allowing continuation of the treatment at the regular dose. CONCLUSION: Our cohort suggests that not all cases of widespread morbilliform rash or atypical erythema multiforme, which occur under treatment with sorafenib or vemurafenib, given for advanced cancer, require discontinuation of therapy. PMID- 26825963 TI - Protective effect of diallylsulphide against mercuric chloride-induced hepatic injury in rats. AB - The present study was undertaken to evaluate the effect of diallylsulphide (DAS) against mercuric chloride (HgCl2)-induced oxidative stress in rat livers. Rats were randomly divided into four groups of six rats each and exposed to HgCl2 (50 mg/kg/body weight (b.w.)) intraperitoneally and/or DAS (200 mg/kg/b.w.) by gavage. HgCl2 administration enhanced alanine aminotransferase (AST) and aspartate aminotransferase (ALT) levels (p < 0.05) with reduction in the levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH Px). However, treatment with DAS markedly attenuated HgCl2-induced biochemical alterations in liver and serum transaminases (AST and ALT; p < 0.05). Further, biochemical results were confirmed by histopathological changes as compared to HgCl2-intoxicated rats. Histopathology of liver also showed that administration of DAS significantly reduced the damage generated by HgCl2 The present study suggests that DAS shows antioxidant activity and plays a protective role against mercury-induced oxidative damage in the rat livers. PMID- 26825964 TI - Alleviation of doxorubicin-induced hepatorenal toxicities with sesamin via the suppression of oxidative stress. AB - Hepatorenal toxicities are an important side effect of anthracycline antibiotics. The objective of this study was to determine whether sesamin (Ses) protects against acute doxorubicin (DOX)-induced hepatorenal toxicities. Rats received daily treatment with either 0.5% carboxymethylcellulose (10 mL/kg) or Ses (10, 20 and 40 mg/kg) orally for 10 days, followed by an intravenous injection at day 8 of either saline (10 mL/kg) or DOX (20 mg/kg). Hepatorenal toxicity was assessed by measuring the levels of serum creatinine (Cre), blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). The protein expression of 4-hydroxynonenal (4-HNE) in hepatorenal tissues was evaluated using immunohistochemistry. The malondialdehyde (MDA) content and antioxidant activity in the kidney and liver tissues were also measured. The results suggest that pretreatment with Ses ameliorated DOX-induced liver and kidney injury by lowering the serum ALT, AST, ALP, Cre and BUN levels (p < 0.05 or p < 0.01), and the histological damage to the liver and kidney tissues induced by DOX compared to control were also significantly attenuated by Ses. Furthermore, Ses significantly decreased the DOX-induced increase of MDA and 4-HNE and increased the activity of CAT, SOD and GPX compared to the DOX-treated rats (p < 0.05 or p < 0.01), whereas the change of DOX + Ses (10 mg/kg) group is not significant compared to the DOX-treated group (p > 0.05). These findings indicate that Ses elicits a typical protective effect against DOX-induced acute hepatorenal toxicity via the suppression of oxidative stress. PMID- 26825965 TI - Classic Spotlight: Quorum Sensing and the Multicellular Life of Unicellular Organisms. PMID- 26825966 TI - Classic Spotlight: a Window on Multicellular Development. PMID- 26825970 TI - Erratum to: High-risk mesothelioma relation to meteorological and geological condition and distance from naturally occurring asbestos. PMID- 26825969 TI - Adapting Behavioral Interventions for Social Media Delivery. AB - Patients are increasingly using online social networks (ie, social media) to connect with other patients and health care professionals--a trend called peer-to peer health care. Because online social networks provide a means for health care professionals to communicate with patients, and for patients to communicate with each other, an opportunity exists to use social media as a modality to deliver behavioral interventions. Social media-delivered behavioral interventions have the potential to reduce the expense of behavioral interventions by eliminating visits, as well as increase our access to patients by becoming embedded in their social media feeds. Trials of online social network-delivered behavioral interventions have shown promise, but much is unknown about intervention development and methodology. In this paper, we discuss the process by which investigators can translate behavioral interventions for social media delivery. We present a model that describes the steps and decision points in this process, including the necessary training and reporting requirements. We also discuss issues pertinent to social media-delivered interventions, including cost, scalability, and privacy. Finally, we identify areas of research that are needed to optimize this emerging behavioral intervention modality. PMID- 26825971 TI - Evaluation of bone mineral density and 25-hydroxyvitamin D levels in subjects with silica exposure. AB - OBJECTIVE: The purpose of the study was to evaluate the bone mineral density (BMD) and 25-hydroxyvitamin D (25(OH)D) levels in patients with silica exposure. MATERIALS AND METHODS: The study included 104 male subjects with silica exposure and 36 healthy subjects. Posterior-anterior radiographs were classified according to the International Labour Office (ILO) Classification. Category 0 patients were classified as Group I (n = 54), category I patients were classified as Group II (n = 25), Category II and III patients were classified as Group III (n = 25). RESULTS: Femoral neck BMD values were significantly lower in Group III (p = 0.007). Lumbar vertebrae BMD values were significantly lower in all groups with silica exposure than in the control group (p = 0.000). The osteoporosis rate was significantly higher in Group III (p = 0.000). Subjects with silica exposure were determined to have diminished 25(OH)D levels (p = 0.012). CONCLUSION: The results of this study demonstrated that subjects with silica exposure have diminished BMD and 25(OH)D levels. PMID- 26825972 TI - Relationships of alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) genotypes with alcohol sensitivity, drinking behavior and problem drinking in Japanese older men. AB - OBJECTIVES: Many East Asians have the genetic polymorphisms rs1229984 in alcohol dehydrogenase 1B (ADH1B) and rs671 in aldehyde dehydrogenase 2 (ALDH2). Here we analyzed the relationships of the two genotypes with alcohol sensitivity, drinking behavior and problem drinking among older and younger men living in rural areas of Japan. METHODS: The subjects were 718 Japanese men aged 63.3 +/- 10.8 (mean +/- SD), categorized into the older (>=65 years, n = 357) and younger (<65 years, n = 361) groups. Facial flushing frequency, drinking behavior and positive CAGE results were compared among the genotypes using Bonferroni corrected chi(2) test and a multivariate logistic regression analysis adjusting for age, BMI and lifestyle factors. RESULTS: The frequency of 'always' facial flushing among the ADH1B*1/*2 carriers was significantly lower than that among the ADH1B*2/*2 carriers in the older group (P < 0.01). The alcohol consumption (unit/day) in the ADH1B*1/*2 carriers tended to be higher compared with that in the ADH1B*2/*2 carriers among the older group (P = 0.050). In the younger group, no significant differences in alcohol sensitivity and drinking habits were generally found among the ADH1B genotypes. The ADH1B*1/*1 genotype tended to be positively associated with problem drinking in the older group (P = 0.080) but not in the younger group. The ALDH2 genotypes consistently and strongly affected the alcohol sensitivity, drinking behavior and problem drinking in both the younger and older group. CONCLUSIONS: We for the first time observed a significant difference in alcohol sensitivity between ADH1B*1/*2 and ADH1B*2/*2 in older men aged 65 and above. PMID- 26825973 TI - Metal-metal bonding and aromaticity in [M2(NHCHNH)3]2 (MU-E)2 (E = O, S; M = Nb, Mo, Tc, Ru, Rh). AB - The nature of M-M bonding and aromaticity of [M2(NHCHNH)3]2(MU-E)2 (E = O, S; M = Nb, Mo, Tc, Ru, Rh) was investigated using atoms in molecules (AIM) theory, electron localization function (ELF), natural bond orbital (NBO) and molecular orbital analysis. These analyses led to the following main conclusions: in [M2(NHCHNH)3]2(MU-E)2 (E = O, S; M = Nb, Mo, Tc, Ru, Rh), the Nb-Nb, Ru-Ru, and Rh-Rh bonds belong to "metallic" bonds, whereas Mo-Mo and Tc-Tc drifted toward the "dative" side; all these bonds are partially covalent in character. The Nb Nb, Mo-Mo, and Tc-Tc bonds are stronger than Ru-Ru and Rh-Rh bonds. The M-M bonds in [M2(NHCHNH)3]2(MU-S)2 are stronger than those in [M2(NHCHNH)3]2(MU-O)2 for M = Nb, Mo, Tc, and Ru. The NICS(1)ZZ values show that all of the studied molecules, except [Ru2(NHCHNH)3]2(MU-O)2, are aromaticity molecules. O-bridged compounds have more aromaticity than S-bridged compounds. Graphical Abstract Left Molecular graph, and right electron localization function (ELF) isosurface of [M2(NHCHNH)3]2(MU-E)2(E = O, S; M = Nb, Mo, Tc, Ru, Rh). PMID- 26825974 TI - A fast loop-closure algorithm to accelerate residue matching in computational enzyme design. AB - Constructing an active site on an inert scaffold is still a challenge in chemical biology. Herein, we describe the incorporation of a Newton-direction-based fast loop-closure algorithm for catalytic residue matching into our enzyme design program ProdaMatch. This was developed to determine the sites and geometries of the catalytic residues as well as the position of the transition state with high accuracy in order to satisfy the geometric constraints on the interactions between catalytic residues and the transition state. Loop-closure results for 64,827 initial loops derived from 21 loops in the test set showed that 99.51% of the initial loops closed to within 0.05 A in fewer than 400 iteration steps, while the large majority of the initial loops closed within 100 iteration steps. The revised version of ProdaMatch containing the novel loop-closure algorithm identified all native matches for ten scaffolds in the native active-site recapitulation test. Its high speed and accuracy when matching catalytic residues with a scaffold make this version of ProdaMatch potentially useful for scaffold selection through the incorporation of more complex theoretical enzyme models which may yield higher initial activities in de novo enzyme design. PMID- 26825977 TI - Women with sleeping problems may be more likely to develop diabetes. PMID- 26825976 TI - Increased left atrial pressure predicts recurrence following successful cryoablation for atrial fibrillation with second-generation cryoballoon. AB - PURPOSE: Several studies have demonstrated that left ventricular diastolic dysfunction (LVDD) and left atrial pressure (LAP), as a surrogate marker of LVDD, were associated with atrial fibrillation (AF) recurrence following radiofrequency catheter ablation (RFCA) for AF. In this study, we aimed to investigate the individual impact of several left ventricular diastolic function parameters on outcomes of cryoablation for paroxysmal AF using second-generation cryoballoon. METHODS: One hundred seventy patients who were scheduled for cryoablation with second-generation cryoballoon were included in this prospective study. All patients underwent comprehensive transthoracic and transesophageal echocardiographic examinations during sinus rhythm a day before catheter ablation. LAP was measured via transseptal sheath at the beginning of the ablation procedure. RESULTS: One hundred seventy patients (57.09 +/- 11.80 years, 47.06 % male) were involved in the study. At a median follow-up of 19 months, when blanking period of 3 months was considered, freedom from AF after a single ablation procedure was 84.71 %. Patients with AF recurrence had significantly greater left atrial volume index (LAVI) (p = 0.005) and LAP (p < 0.001). Patients with AF recurrence had lower septal e' wave (p = 0.013), and higher E/e' ratio (p = 0.014). LAVI (p = 0.007) and LAP (p = 0.006) were independent predictors of AF recurrence. A cut-off value of 13.50 mmHg for LAP measured during the procedure was associated with a sensitivity and specificity of 80.8 and 84.7 % (p = 0.005) for predicting AF recurrence. CONCLUSIONS: Pre-procedural LAVI and procedural LAP measurement have clinical importance in predicting AF recurrence in patients undergoing cryoablation with second-generation cryoballoon. Effectiveness of cryoablation is reduced in patients with greater LAVI and LAP. PMID- 26825975 TI - A Pilot Study of a Readiness Group to Increase Initiation of Smoking Cessation Services among Women in Residential Addiction Treatment. AB - This study implemented a smoking cessation readiness group (RG) in two women focused residential substance abuse treatment programs, with the aim of engaging women in smoking cessation services. The primary outcome was defined as attending at least one cessation group after the RG ended. The RG combined features of the Expert Systems (ES) approach with a practice quit attempt. ES is an interactive system which tailors intervention to the smokers' stage of change, while the practice quit attempt rehearses the process of quitting smoking. As a secondary aim we tested whether incentives, used to promote participation and engagement in the RG, would increase initiation of smoking cessation services. Participants (N=75) were women smokers enrolled in two residential programs, and intention to quit smoking was not required for participation. Twelve participant cohorts were randomly assigned to receive the RG with or without incentives. Following the RG intervention, 38.7% of participants (n=29) attended at least one smoking cessation session. Both the number of RG sessions attended and a successful practice quit attempt predicted the later use of cessation services, while incentives did not. From pre- to post-RG, participants reported decreased cigarettes per day (CPD: 11.8 vs. 7.6, p<.0001) and decreased nicotine dependence as measured by the Heaviness Smoking Index (HSI: 2.3 vs. 1.8, p<.001). The 3 session group-format RG intervention was associated with initiation of smoking cessation services and with changes in smoking behavior. PMID- 26825978 TI - Erratum to: UBE2S is associated with malignant characteristics of breast cancer cells. PMID- 26825979 TI - Erratum to: FAM98A is a novel substrate of PRMT1 required for tumor cell migration, invasion and colony formation. PMID- 26825980 TI - Analysis of Helicobacter pylori genotypes in clinical gastric wash samples. AB - Helicobacter pylori is a key factor in the development of gastric cancer; indeed, clearance of H. pylori helps prevent gastric cancer. However, the relationship between gastric cancer and the abundance and diversity of H. pylori genotypes in the stomach remains unknown. Here, we present, for the first time, a quantitative analysis of H. pylori genotypes in gastric washes. A method was first developed to assess diversity and abundance by pyrosequencing and analysis of single nucleotide polymorphisms in 23S ribosomal RNA (rRNA), a gene associated with clarithromycin resistance. This method was then validated using arbitrarily mixed plasmids carrying 23S rRNA with single nucleotide polymorphisms. Multiple strains were detected in many of 34 clinical samples, with frequency 24.3 +/- 24.2 and 26.3 +/- 33.8 % for the A2143G and A2144G strains, respectively. Importantly, results obtained from gastric washes were similar to those obtained from biopsy samples. The method provides opportunities to investigate drug resistance in H. pylori and assess potential biomarkers of gastric cancer risk, and should thus be validated in large-scale clinical trials. PMID- 26825981 TI - DeltaNp63 regulates cell proliferation, differentiation, adhesion, and migration in the BL2 subtype of basal-like breast cancer. AB - Triple-negative breast cancers (TNBC) comprise a heterogeneous subgroup of tumors with a generally poor prognosis. Subclassification of TNBC based on genomic analyses shows that basal-like TNBCs, specifically the basal A or BL2 subtype, are characterized by the expression of DeltaNp63, a transcription factor that has been attributed a variety of roles in the regulation of proliferation, differentiation, and cell survival. To investigate the role(s) of p63 in basal like breast cancers, we used HCC1806 cells that are classified as basal A/BL2. We show that these cells endogenously express p63, mainly as the DeltaNp63alpha isoform. TP63 gene knockout by CRISPR resulted in viable cells that proliferate more slowly and adhere less tightly, with an increased rate of migration. Analysis of adhesion-related gene expression revealed a complex set of alterations in p63-depleted cells, with both increased and decreased adhesion molecules and adhesion substrates compared to parental cells expressing p63. Examination of the phenotype of these cells indicated that endogenous p63 is required to suppress the expression of luminal markers and maintain the basal epithelial phenotype, with increased levels of both CK8 and CK18 and a reduction in N-cadherin levels in cells lacking p63. On the other hand, the level of CK5 was not decreased and ER was not increased, indicating that p63 loss is insufficient to induce full luminal-type differentiation. Taken together, these data demonstrate that p63 exerts multiple pro-oncogenic effects on cell differentiation, proliferation and adhesion in basal-like breast cancers. PMID- 26825982 TI - MIIP expression predicts outcomes of surgically resected esophageal squamous cell carcinomas. AB - The migration and invasion inhibitory protein (MIIP) was shown to function as a tumor suppressor gene in gliomas by inhibiting tumor cell growth, migration, and invasion. However, its role and clinical significance in esophageal squamous cell carcinoma (ESCC) have not been elucidated. We investigated the correlation of MIIP expression and clinical outcome in a group of surgically resected ESCCs. Tissue microarrays constructed of 253 surgically resected ESCC primary tumors and paired paracancerous normal esophageal epithelia were used for MIIP evaluation by immunohistochemistry. The clinical and prognostic significance of MIIP expression was analyzed statistically. The expression of MIIP expression in cancer tissues was increased significantly in comparison with the paired paracancerous normal epithelia (P < 0.001). And, MIIP expression was associated with ESCC cells' differentiation (P < 0.001). By Kaplan-Meier analysis, patients with low MIIP expression exhibited significantly improved overall survival (OS, P = 0.039) and a tendency of improved disease-free survival (DFS, P = 0.086) than those with high MIIP expression. In addition, MIIP expression could distinguish OS or DFS of patients with tumors in stage T3-4 (P = 0.020, 0.028), N0 (P = 0.008, 0.032), and stage II (P = 0.004, 0.019), as well as at lower thoracic esophagus (P = 0.024, 0.090). Multivariate analysis showed that MIIP expression was an independent prognostic factor in ESCC OS and DFS. In conclusion, MIIP expressed higher in ESCCs than in paracancerous normal esophageal epithelia and was a positive, independent prognostic factor in resected ESCCs. PMID- 26825983 TI - Evaluation of mRNA expression levels of IL-17A and IL-10 cytokines in cervical cancer. AB - In this study, we evaluated mRNA expression levels of interleukin (IL)-10/IL-17A by quantitative real-time PCR and their clinical importance in cervical cancer. The IL-10 mRNA levels were higher in cervical cancer tissues as compared with corresponding normal tissues (p < 0.05). Moreover, IL-17A mRNA was significantly increased in cervical cancer tissues than in normal tissues (p < 0.05). Moreover, the high expression level of IL-10 mRNA was markedly related to International League of Gynecology and Obstetrics (FIGO) stage (p = 0.001), but no significant association was found with other clinical factors including age, tumor size, histological grades, and lymph node metastasis. Moreover, high expression levels of IL-17A were not associated with patients' age, tumor size, FIGO stage, and histological grades while IL-17A expression was strongly linked to lymphatic metastasis (p = 0.001). These findings showed that IL-17A might have a crucial role in cervical cancer metastasis. Taken together, IL-17A expression was strongly linked to lymphatic metastasis, indicating that IL-17A might have a crucial role in cervical cancer metastasis. Moreover, our study suggested the association of IL-10 mRNA expression with clinical stage. PMID- 26825984 TI - Characterization of ceftriaxone-resistant Aeromonas spp. isolates from stool samples of both children and adults in Southern India. AB - BACKGROUND: Aeromonas species can cause a wide spectrum of illnesses varying from intestinal to extra intestinal and vary in their susceptibility to different antibiotics. The current study was undertaken to characterize the third generation cephalosporin-resistant strains of Aeromonas spp. which were isolated from stool specimens. METHODS: Out of a total of 2780 stool samples, 29 Aeromonas spp. were identified, out of which, 9 were resistant to ceftriaxone by the Kirby Bauer antibiotic testing method. These strains were subjected to minimum inhibitory concentration (MIC) determination by agar dilution for ceftriaxone. Phenotypic and genotypic testing of AmpC beta-lactamase and extended spectrum beta-lactamase (ESBL) were performed. Gene transfer was carried out to demonstrate transmissibility of these genetic elements by conjugation experiments. RESULTS: Out of the 29 strains, 9 showed MIC of >=4 MUg/ml. Seven out of 9 showed presence of blaCTX-M, while 2 more strains showed the presence of inducible AmpC beta-lactamase and presence of MOX gene. Gene transfer experiments showed that these elements were transmissible to recipient (Escherichia coli J53 strain) in the presence of ceftriaxone. CONCLUSIONS: Dissemination of these resistance determinants like plasmids is pivotal in the spread of these resistance genes into the aquatic environment into organisms like Aeromonas. This may further limit the future use of antibiotics for the treatment of diarrhoeal diseases. Hence, detection and antibiotic susceptibility testing of Aeromonas spp. should be performed when isolated from stool samples. PMID- 26825985 TI - 5 years after an ACE: what happens then? AB - PURPOSE: Antegrade continence enema (ACE) revolutionised the lives of children with chronic constipation and soiling. Parents often ask how long the ACE will be required. We looked at our patients 5 years after ACE formation to answer the question. METHODS: We reviewed clinical notes of all patients undergoing ACE procedure during January 1990 to December 2010. Only patients with >5 years follow-up were included. Data are given as median (range). RESULTS: 133 patients were included with >5 years of follow-up. Primary pathology was anorectal anomaly (ARA) 64 (48%); spinal dysraphism (SD) 40 (30%); functional constipation (FC) 14 (10%); Hirschsprung's Disease (HD) 10 (8%) and others 5 (4%). Median follow-up was 7 years (5-17 years). Overall 74% still use their ACE; whilst 26% no longer access their stoma, of whom 47% recovered normal colonic function. 50% of HD patient recover colonic function. FC has the highest failure rate at 21%. CONCLUSIONS: Overall 86% achieved excellent clinical outcome with 74% of patient still using their ACE at 5 years. HD has the highest recovery rate of 50%. FC has a more unreliable clinical outcome with 21% recovered colonic function and 21% failed. Outcome varied dependent on the background diagnosis. PMID- 26825986 TI - Posterior corneal astigmatism in refractive lens exchange surgery. AB - PURPOSE: To assess the anterior, posterior and total corneal spherical and astigmatic powers in patients undergoing refractive lens exchange (RLE) surgery. METHODS: In 402 consecutive patients planned for RLE at Koskelas Eye Clinic, Lulea, Sweden, right eye data from pre- and postoperative subjective refraction, preoperative IOLMaster((r)) biometry and Pentacam HR((r)) measurements were collected. Postoperative Pentacam HR((r)) data were collected for 54 of the patients. The spherical and astigmatic powers of the anterior and posterior corneal surfaces and for the total cornea were assessed and compared, and surgically, induced astigmatism was calculated using vector analysis. RESULTS: The spherical power of the anterior corneal surface was 48.18 +/- 1.69D with an astigmatic power of 0.83 +/- 0.54D. The corresponding values for the posterior surface were -6.05 +/- 2,52D and 0.26 +/- 0.15D, respectively. The total corneal spherical power calculated with ray tracing was 42.47 +/- 2.89D with a 0.72 +/- 0.48D astigmatic power, and the corresponding figures obtained by estimating the posterior corneal surface were 43.25 +/- 1.51D (p < 0.001) with a 0.75 +/- 0.49D astigmatic power (p = 0.003). In eyes with anterior astigmatism with-the-rule, the total corneal astigmatism is overestimated if the posterior corneal surface is estimated; in eyes, with against-the-rule astigmatism it is underestimated. Had the posterior corneal surface been measured in this material, 14.7% of the patients would have received a spheric instead of a toric IOL, or vice versa. CONCLUSION: Estimating the posterior corneal surface in RLE patients leads to systematic measurement errors that can be reduced by measuring the posterior surface. Such an approach can potentially increase the refractive outcome accuracy in RLE surgery. PMID- 26825987 TI - Engineering of Bacillus subtilis for the Production of 2,3-Butanediol from Sugarcane Molasses. AB - 2,3-butanediol is known to be a platform chemical with several potential industrial applications. Sustainable industrial scale production can be attained by using a sugarcane molasses based fermentation process using Bacillus subtilis. However, the accumulation of acetoin needs to be reduced to improve process efficiency. In this work, B. subtilis was genetically modified in order to increase the yield of 2,3-butanediol. Metabolic engineering strategies such as cofactor engineering and overexpression of the key enzyme butanediol dehydrogenase were attempted. Both the strategies individually led to a statistically significant increase in the 2,3-butanediol yields for sugarcane molasses based fermentation. Cofactor engineering led to a 26 % increase in 2,3 butanediol yield and overexpression of bdhA led to a 11 % increase. However, the combination of the two strategies did not lead to a synergistic increase in 2,3 butanediol yield. PMID- 26825988 TI - Caesarean delivery and its correlates in Northern Region of Bangladesh: application of logistic regression and cox proportional hazard model. AB - BACKGROUND: Caesarean delivery (C-section) rates have been increasing dramatically in the past decades around the world. This increase has been attributed to multiple factors such as maternal, socio-demographic and institutional factors and is a burning issue of global aspect like in many developed and developing countries. Therefore, this study examines the relationship between mode of delivery and time to event with provider characteristics (i.e., covariates) respectively. METHODS: The study is based on a total of 1142 delivery cases from four private and four public hospitals maternity wards. Logistic regression and Cox proportional hazard models were the statistical tools of the present study. RESULTS: The logistic regression of multivariate analysis indicated that the risk of having a previous C-section, prolonged labour, higher educational level, mother age 25 years and above, lower order of birth, length of baby more than 45 cm and irregular intake of balanced diet were significantly predict for C-section. With regard to survival time, using the Cox model, fetal distress, previous C-section, mother's age, age at marriage and order of birth were also the most independent risk factors for C section. By the forward stepwise selection, the study reveals that the most common factors were previous C-section, mother's age and order of birth in both analysis. As shown in the above results, the study suggests that these factors may influence the health-seeking behaviour of women. CONCLUSIONS: Findings suggest that program and policies need to address the increase rate of caesarean delivery in Northern region of Bangladesh. Also, for determinant of risk factors, the result of Akaike Information Criterion (AIC) indicated that logistic model is an efficient model. PMID- 26825990 TI - Use of an Intrathecal Catheter for Analgesia, Anesthesia, and Therapy in an Obstetric Patient with Pseudotumor Cerebri Syndrome. AB - Pseudotumor cerebri syndrome (PTCS) is a rare disorder chiefly observed in obese women of childbearing age. We describe a case of a parturient with PTCS managed successfully with an intrathecal catheter, after inadvertent dural puncture, for labor analgesia, surgical anesthesia, and treatment of headache because of intracranial hypertension during the peripartum period. Prolonged placement of the intrathecal catheter (i.e., >24 hours) may have contributed to the absence of postdural puncture headache symptoms and an uneventful postpartum period. Intrathecal catheter placement may therefore be a viable option in patients with PTCS should inadvertent dural puncture occur. PMID- 26825991 TI - A Delayed Complication of Temporal Craniotomy Leading to a Potentially Difficult Airway. AB - Pseudoankylosis of the temporomandibular joint may occur as a complication of frontotemporal craniotomy. We report a patient who presented for surgery with a restricted mouth opening resulting from an infectious complication after frontotemporal craniotomy. Early identification of the potentially difficult airway helped manage this patient. We explain the mechanism of this late complication that may result in a difficult airway. If this is not identified preoperatively when a patient presents for emergency surgery or when the patient is in altered sensorium, it may lead to an unanticipated difficult airway. PMID- 26825989 TI - Enhanced gefitinib-induced repression of the epidermal growth factor receptor pathway by ataxia telangiectasia-mutated kinase inhibition in non-small-cell lung cancer cells. AB - The epidermal growth factor receptor (EGFR) tyrosine kinase signaling pathways regulate cellular activities. The EGFR tyrosine kinase inhibitors (EGFR-TKIs) repress the EGFR pathway constitutively activated by somatic EGFR gene mutations and have drastically improved the prognosis of non-small-cell lung cancer (NSCLC) patients. However, some problems, including resistance, remain to be solved. Recently, combination therapy with EGFR-TKIs and cytotoxic agents has been shown to improve the prognosis of NSCLC patients. To enhance the anticancer effects of EGFR-TKIs, we examined the cross-talk of the EGFR pathways with ataxia telangiectasia-mutated (ATM) signaling pathways. ATM is a key protein kinase in the DNA damage response and is known to phosphorylate Akt, an EGFR downstream factor. We found that the combination of an ATM inhibitor, KU55933, and an EGFR TKI, gefitinib, resulted in synergistic cell growth inhibition and induction of apoptosis in NSCLC cell lines carrying the sensitive EGFR mutation. We also found that KU55933 enhanced the gefitinib-dependent repression of the phosphorylation of EGFR and/or its downstream factors. ATM inhibition may facilitate the gefitinib-dependent repression of the phosphorylation of EGFR and/or its downstream factors, to exert anticancer effects against NSCLC cells with the sensitive EGFR mutation. PMID- 26825992 TI - Seizure After Abdominal Surgery in an Infant Receiving a Standard-Dose Postoperative Epidural Bupivacaine Infusion. AB - We present the case of an otherwise healthy 12-month-old girl undergoing repair of a giant omphalocele, who experienced a postoperative seizure attributed to accumulation of bupivacaine from an epidural infusion. Whereas a standard dose was used, this patient experienced temporary liver dysfunction postoperatively, presumably from elevated intra-abdominal pressures, predisposing her to toxicity after a prolonged infusion. This case illustrates how the type of surgery can influence the margin of safety of routinely used neuraxial local anesthetic doses in infants and young children. PMID- 26825993 TI - The Diagnosis and Management of Patient with Delayed Symptoms from a Tracheal Tear. AB - Development of subcutaneous emphysema after gastrointestinal endoscopy with general anesthesia presents a diagnostic conundrum. We discuss the management of a patient who experienced significant vomiting followed by neck and facial swelling with crepitus and shortness of breath after the endoscopic retrograde cholangiopancreatography. The presence of respiratory distress usually suggests that head and neck subcutaneous emphysema is most likely associated with pneumothorax and/or pneumomediastinum. We discuss the prevention, differential diagnosis, and current management of tracheal tears including subcutaneous emphysema. PMID- 26825994 TI - Normoglycemic Diabetic Ketoacidosis in a Pregnant Patient with Type II Diabetes Mellitus Presenting for Emergent Cesarean Delivery. AB - The development of acute abdominal pain in a laboring parturient after a previous cesarean delivery is of concern and may be the result of a potentially life threatening condition such as uterine rupture. We present a case of a parturient with type II diabetes mellitus, who had undergone 2 previous cesarean deliveries and now presented in labor with increasing abdominal pain. An emergency cesarean delivery was performed for probable uterine rupture. Intraoperatively, the patient was noted to be severely hypocarbic with significant metabolic acidosis, and the diagnosis of diabetic ketoacidosis was established. PMID- 26825995 TI - Fluoroscopically guided lumbar facet joint injection using an interlaminar approach and loss of resistance technique. AB - PURPOSE: To describe a new technique for performing fluoroscopically guided lumbar facet joint injections using an interlaminar approach and loss-of resistance technique and to report the initial success rate of this technique in a small series of patients. MATERIALS AND METHODS: The institutional radiology database was retrospectively reviewed to identify patients who underwent fluoroscopically guided lumbar facet joint injections. Between 1 May 2014 and 31 October 2015, one radiologist attempted fluoroscopically guided lumbar facet joint injections using an interlaminar approach and loss-of-resistance technique in ten severely osteoarthritic facet joints (4 patients). Patient demographics, facet joint side and level, and whether or not an intra-articular facet joint injection was achieved were recorded. RESULTS: Intra-articular injection was achieved using the interlaminar approach and loss-of-resistance technique in five facet joints. CONCLUSION: Fluoroscopically guided lumbar facet joint injection using an interlaminar approach and loss-of-resistance technique is an alternative approach to a direct posterior facet joint injection and may be particularly useful for severely osteoarthritic facet joints, where bulky osteophytes and/or extreme curvature of the joints in the transverse plane threaten to preclude direct posterior access to the joints. PMID- 26825996 TI - The assessment of multifocal ERG responses in school-age children with history of prematurity. AB - PURPOSE: The authors examined macular function in preterm-born children, using multifocal ERG (mfERG). Possible alterations in P1 amplitudes, P1 amplitudes density and P1 implicit time between school-age children with history of prematurity and their peers were researched. The correlations between parameters of mfERG responses and birth weight, gestational age, macular volume and central macular thickness were verified. METHODS: A group of 18 preterm-born school-age children were analyzed (mean age 10.18 +/- 1.21 years). The study group was compared to the group of 15 peers born appropriate for gestational age (mean age 10.8 +/- 1.52 years). The mfERG was evaluated in all children. RESULTS: There were statistically significant differences for P1 amplitudes from ring 1 (p = 0.0001) and P1 amplitudes density from ring 1 (p = 0.0001). Calculating the correlation coefficients, we receive significant results for P1 amplitudes from ring 1 versus gestational age (r = 0.54; p = 0.026), birth weight (r = 0.54; p = 0.026) and central macular thickness (r = -0.62; p = 0.008), and for P1 amplitudes density from ring 1 versus central macular thickness (r = -0.51; p = 0.034). CONCLUSIONS: The study suggests that P1 amplitudes and P1 amplitudes density vary in preterm-born children in comparison with their peers born appropriate for gestational age, which might suggest discreet macular dysfunction. The correlation between low birth weight, early gestational age, central macular thickness and mFERG components from ring 1 might evidence that decreased bipolar cells density caused by premature birth is the result of altered development of central retina reflecting in structural anomalies of the fovea. PMID- 26825997 TI - Muscarinic acetylcholine receptor M1 and M3 subtypes mediate acetylcholine induced endothelium-independent vasodilatation in rat mesenteric arteries. AB - The present study investigated pharmacological characterizations of muscarinic acetylcholine receptor (AChR) subtypes involving ACh-induced endothelium independent vasodilatation in rat mesenteric arteries. Changes in perfusion pressure to periarterial nerve stimulation and ACh were measured before and after the perfusion of Krebs solution containing muscarinic receptor antagonists. Distributions of muscarinic AChR subtypes in mesenteric arteries with an intact endothelium were studied using Western blotting. The expression level of M1 and M3 was significantly greater than that of M2. Endothelium removal significantly decreased expression levels of M2 and M3, but not M1. In perfused mesenteric vascular beds with intact endothelium and active tone, exogenous ACh (1, 10, and 100 nmol) produced concentration-dependent and long-lasting vasodilatations. In endothelium-denuded preparations, relaxation to ACh (1 nmol) disappeared, but ACh at 10 and 100 nmol caused long-lasting vasodilatations, which were markedly blocked by the treatment of pirenzepine (M1 antagonist) or 4-DAMP (M1 and M3 antagonist) plus hexamethonium (nicotinic AChR antagonist), but not methoctramine (M2 and M4 antagonist). These results suggest that muscarinic AChR subtypes, mainly M1, distribute throughout the rat mesenteric arteries, and that activation of M1 and/or M3 which may be located on CGRPergic nerves releases CGRP, causing an endothelium-independent vasodilatation. PMID- 26825998 TI - Culture X: addressing barriers to physical activity in Samoa. AB - There is an urgent need to address the epidemic rates of non-communicable diseases globally, and the Pacific Island region is of particular concern. Increasing physical activity participation plays an important role in reducing some of the key risk factors for non-communicable diseases including obesity and being overweight. In order to address low levels of physical activity, it is essential to understand the key barriers and facilitating factors experienced by specific population groups. The purpose of this study is to investigate key facilitating factors for participation in a dance aerobic initiative, Culture X, developed in the Pacific Island country, Samoa. The study further aims to understand ways in which the programme assists participants in addressing barriers to physical activity. Face-to-face interviews running from 10 to 20 min were conducted with 28 Culture X participants in order to gain a deep understanding of participants' personal perspectives with regard to barriers and facilitating factors to physical activity. Findings suggest the inclusion of key cultural components (including, traditional dance moves and music, prayer, community orientation and family inclusiveness) were integral for supporting ongoing participation in Culture X. These components further assisted participants in addressing important personal and social barriers to physical activity (including lack of motivation and enjoyment, lack of confidence, time management, family and social commitments and lack of support). This study highlights creative ways that health promotion in the Pacific Island region can encourage physical activity and informs health promotion literature regarding the importance of placing local culture at the heart of behaviour change initiatives. PMID- 26826002 TI - Interleukin-17A gene polymorphism with the susceptibility of intestinal symptoms in patients with Behcet's disease. PMID- 26826001 TI - Hepatic IGF-1R overexpression combined with the activation of GSK-3beta and FOXO3a in the development of liver cirrhosis. AB - AIMS: Liver cirrhosis is the common pathological histology manifest among a number of chronic liver diseases and liver cancer. Circulating levels of insulin growth factor-1 (IGF-1) have been recently linked to liver cirrhosis and the development of liver cancer. Herein, we hypothesized that IGF-1R overexpression combining the activation of GSK-3beta and FOXO3a were involved in the development of human and murine chronic liver cirrhosis. METHODS: Liver samples of patients were screened from the Tissue Bank of the China-Japan Union Hospital of Jilin University. Mice liver fibrosis model was performed using intraperitoneal injection of carbon tetrachloride (CCl4) for 12weeks. Serum IGF-1 levels were detected by enzyme-linked immunosorbent assays (ELISA). Microscopical examination of liver parenchyma was performed using conventional H&E and Masson's staining. Moreover, we investigated the IGF-1 receptor (IGF-1R) signaling pathway at different period after CCl4 administration. RESULTS: Serum IGF-1 levels were significantly decreased in patients with liver cirrhosis, which is concomitant with the declined circulating levels of IGF-1 in 8 to 12weeks CCl4-treated mice. Furthermore, the expression of IGF-1R was significantly higher at 12w compared with control group. In addition, activation of the GSK-3beta and FOXO3a were activated during the process of murine chronic liver injury. CONCLUSION: The present study demonstrates that decreased circulating IGF-1 levels are involved in human and murine chronic liver disease. Interestingly, overexpression of the IGF-1R, and activation of GSK3beta and FOXO3a might be the molecular mechanisms underlying the development of liver cirrhosis. PMID- 26826003 TI - Validity of the Japanese Orthopaedic Association scoring system based on patient reported improvement after posterior lumbar interbody fusion. AB - BACKGROUND CONTEXT: The Japanese Orthopaedic Association (JOA) scoring system is a physician-based outcome that has been used to evaluate treatment effectiveness after lumbar surgery. However, patient-centered evaluation becomes increasingly important. There is no study that has examined the relationship between the JOA scoring system and patients' self-reported improvement. PURPOSE: The purpose of the present study was to validate the JOA scoring system for assessment of patient-reported improvement after lumbar surgery. STUDY DESIGN: This is a retrospective review of prospectively collected data. PATIENT SAMPLE: The patient sample included 273 mail-in responders of the 466 consecutive patients who underwent posterior lumbar interbody fusion for spondylolisthesis between 1996 and 2008 in a single hospital. OUTCOME MEASURES: The outcome measures were the JOA scoring system and patients' self-reported improvement. METHODS: Two hundred seventy three patients were divided into five anchoring groups based on self reported improvement from "Much better" to "Much worse." Outcomes (ie, recovery rate, amount of change from preoperative condition, and postoperative score) based on the JOA scoring system were compared among groups. Using the patient's self-reported improvement scale as an anchor, the association among each of the outcomes was examined. The cutoff point and the area under the curve (AUC) that differentiated "Improved" from "Neither improved nor worse" was calculated using receiver operating characteristic (ROC) curve analysis. RESULTS: The recovery rate and postoperative score were significantly different in 9 of 10 pairs of anchoring groups. The amount of change was significantly different in six pairs. Spearman correlation coefficient for the 5-point scale anchors of patients' self reported improvement was 0.20 (p=.001) for the baseline score, 0.31 (p<.001) for the amount of change, 0.55 (p<.001) for the recovery rate, and 0.56 (p<.001) for the postoperative score. According to ROC analysis, the best cutoff points and AUCs were 13 points and 0.69, respectively, for the amount of change, 67% and 0.73, respectively, for recovery rate, and 23 points and 0.72, respectively, for postoperative score. CONCLUSIONS: The JOA scoring system is a valid method for assessment of patients' self-reported improvement. Patients' self-reported improvement is more likely to be associated with the final condition, such as postoperative score or recovery rate, rather than the change from the preoperative condition. PMID- 26826004 TI - Intraspecific trait variation drives functional responses of old-field plant communities to nutrient enrichment. AB - Environmental changes are expected to shift the distribution of functional trait values in plant communities through a combination of species turnover and intraspecific variation. The strength of these shifts may depend on the availability of individuals with trait values adapted to new environmental conditions, represented by the functional diversity (FD) of existing community residents or dispersal from the regional species pool. We conducted a 3-year nutrient- and seed-addition experiment in old-field plant communities to examine the contributions of species turnover and intraspecific variation to community trait shifts, focusing on four key plant functional traits: vegetative height, leaf area, specific leaf area (SLA), and leaf dry matter content (LDMC). We further examined the influence of initial FD and seed availability on the strength of these shifts. Community mean height, leaf area, and SLA increased in response to fertilization, and these shifts were driven almost entirely by intraspecific variation. The strength of intraspecific shifts in height and leaf area was positively related to initial intraspecific FD in these traits. Intraspecific trait responses to fertilization varied among species, with species of short stature displaying stronger shifts in SLA and LDMC but weaker shifts in leaf area. Trait shifts due to species turnover were generally weak and opposed intraspecific responses. Seed addition altered community taxonomic composition but had little effect on community trait shifts. These results highlight the importance of intraspecific variation for short-term community functional responses and demonstrate that the strength of these responses may be mediated by community FD. PMID- 26826005 TI - Erratum to: Temperature, precipitation and biotic interactions as determinants of tree seedling recruitment across the tree line ecotone. PMID- 26826006 TI - Topiramate for cocaine dependence: a systematic review and meta-analysis of randomized controlled trials. AB - AIMS: To assess the efficacy of topiramate in treating cocaine use disorder (i.e. retention, efficacy, safety and craving reduction) through a systematic review and meta-analysis. METHODS: We searched six scientific databases from inception to 23 December 2014 with no date limits. Data were reviewed, extracted and analysed systematically. Studies were included if they were peer-reviewed randomized control trials with participants meeting diagnostic criteria for cocaine dependence or cocaine use disorder, with the treatment arm involving topiramate with or without psychosocial intervention, and the control arm involving no intervention or psychosocial intervention with or without placebo. A random-effects meta-analytical model was computed. RESULTS: Five studies met inclusion criteria (n = 518). Topiramate was compared with placebo (four studies) and no medication (one study). In a meta-analysis, we observed no significant differences between topiramate and placebo in improving treatment retention risk ratio (RR) = 0.85; 95% confidence interval (CI) = 0.60-1.22, P = 0.38. However, compared with a placebo, use of topiramate was associated with increased continuous abstinence in two of five studies (RR = 2.43; 95% CI = 1.31-4.53, P = 0.005). No differences were observed in frequency of adverse effects reported between topiramate and placebo (RR = 1.06; 95% CI = 0.91-1.23, P = 0.48). Topiramate was associated significantly (P < 0.05) with a reduction in craving in only one of five studies. CONCLUSIONS: Evidence does not currently support the use of topiramate to improve treatment retention for cocaine use disorder, although it may extend cocaine abstinence with a similar risk of adverse events compared with placebo. PMID- 26826008 TI - Dose-dependent inhibition of GCPII to prevent and treat cognitive impairment in the EAE model of multiple sclerosis. AB - There are no treatments for cognitive impairment in multiple sclerosis (MS). Novel treatments can be evaluated in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS that displays both physical and cognitive impairments. Inhibition of the neuropeptidase glutamate carboxypeptidase II (GCPII) has previously been shown to ameliorate cognitive impairment in EAE, but dosing has not yet been optimized and only a prevention treatment paradigm has been explored. In the study described herein, the dose response of the GCPII inhibitor 2-(phosphonomethyl)pentanedioic acid (2-PMPA) was evaluated for preventing cognitive impairment in EAE mice. Mice were immunized and received daily injections of vehicle or 2-PMPA (10, 30, 100, or 300 mg/kg) from the time of immunization (i.e. day 0). Although no doses of the drug altered physical disease severity, the 100mg/kg dose was most efficacious at preventing cognitive impairments in Barnes maze performance. Dose-related increases in brain NAAG levels were observed in post-mortem analysis, confirming target engagement. Using the 100mg/kg dose, we subsequently evaluated 2-PMPA's ability to treat EAE induced symptoms by commencing treatment after the onset of physical signs of EAE (i.e. day 14). Mice were immunized for EAE and received daily injections of vehicle or 100mg/kg 2-PMPA starting two weeks post-immunization. Significant improvements in both cognitive performance and increases in brain NAAG levels were observed. GCPII inhibition is a promising treatment for cognitive impairment in MS, and doses providing equivalent exposures to 100mg/kg 2-PMPA in mice should be evaluated in clinical studies for the prevention and/or treatment of MS related cognitive impairment. PMID- 26826007 TI - Role of alpha4-containing GABAA receptors in limiting synaptic plasticity and spatial learning of female mice during the pubertal period. AB - Expression of alpha4betadelta GABAA receptors (GABARs) increases at the onset of puberty on dendritic spines of CA1 hippocampal pyramidal cells. These receptors reduce activation of NMDA receptors (NMDARs), impair induction of long-term potentiation (LTP) and reduce hippocampal-dependent spatial learning. These effects are not seen in the delta-/- mouse, implicating alpha4betadelta GABARs. Here we show that knock-out of alpha4 also restores synaptic plasticity and spatial learning in female mice at the onset of puberty (verified by vaginal opening). To this end, field excitatory post-synaptic potentials (fEPSPs) were recorded from the stratum radiatum of CA1 hippocampus in the slice from +/+ and alpha4-/- pubertal mice (PND 35-44). Induction of LTP, in response to stimulation of the Schaffer collaterals with theta burst stimulation (TBS), was unsuccessful in the +/+ hippocampus, but reinstated by alpha4 knock-out (~65% potentiation) but not by blockade of alpha5-GABARs with L-655,708 (50nM). In order to compare spatial learning in the two groups of mice, animals were trained in an active place avoidance task where the latency to first enter a shock zone is a measure of learning. alpha4-/- mice had significantly longer latencies by the third learning trial, suggesting better spatial learning, compared to +/+ animals, who did not reach the criterion for learning (120s latency). These findings suggest that knock-out of the GABAR alpha4 subunit restores synaptic plasticity and spatial learning at puberty and is consistent with the concept that the dendritic alpha4betadelta GABARs which emerge at puberty selectively impair CNS plasticity. This article is part of a Special Issue entitled SI: Adolescent plasticity. PMID- 26826009 TI - Hydrogen-rich water attenuates brain damage and inflammation after traumatic brain injury in rats. AB - Inflammation and oxidative stress are the two major causes of apoptosis after traumatic brain injury (TBI). Most previous studies of the neuroprotective effects of hydrogen-rich water on TBI primarily focused on antioxidant effects. The present study investigated whether hydrogen-rich water (HRW) could attenuate brain damage and inflammation after traumatic brain injury in rats. A TBI model was induced using a controlled cortical impact injury. HRW or distilled water was injected intraperitoneally daily following surgery. We measured survival rate, brain edema, blood-brain barrier (BBB) breakdown and neurological dysfunction in all animals. Changes in inflammatory cytokines, inflammatory cells and Cho/Cr metabolites in brain tissues were also detected. Our results demonstrated that TBI-challenged rats exhibited significant brain injuries that were characterized by decreased survival rate and increased BBB permeability, brain edema, and neurological dysfunction, while HRW treatment ameliorated the consequences of TBI. HRW treatment also decreased the levels of pro-inflammatory cytokines (TNF alpha, IL-1beta and HMGB1), inflammatory cell number (Iba1) and inflammatory metabolites (Cho) and increased the levels of an anti-inflammatory cytokine (IL 10) in the brain tissues of TBI-challenged rats. In conclusion, HRW could exert a neuroprotective effect against TBI and attenuate inflammation, which suggests HRW as an effective therapeutic strategy for TBI patients. PMID- 26826011 TI - Consequences and treatment of guidewire entrapment and fracture during percutaneous coronary intervention. AB - Guidewire fracture is an uncommon, yet feared complication of percutaneous coronary intervention that may be more likely to occur in complex lesions and when guidewires interact with newly deployed or pre-existing stents. Wire fragments can often be retrieved using percutaneous techniques, but may need to be removed surgically in case of percutaneous retrieval failure. We present two cases of guidewire entrapment and fracture. In the first case the fractured polymer-jacketed guidewire was successfully retrieved, after crossing the lesion with another guidewire and performing balloon dilation next to the entrapped guidewire. In the second case, attempts for percutaneous guidewire retrieval failed. The wire fragment protruded into the ascending aorta leading to emergent cardiac surgery. We also reviewed the published literature on guidewire fracture and entrapment since 2007, providing an update on risk factors, consequences, and managements of this complication. PMID- 26826010 TI - Effects of stroke severity and treatment duration in normobaric hyperoxia treatment of ischemic stroke. AB - In order to improve clinical trial design and translation of normobaric oxygen (NBO) treatment of ischemic stroke, NBO treatment parameters need to be better understood. This study investigated NBO treatment efficacy at two different stroke severities and two NBO treatment durations in rats. For the 60-min middle cerebral artery occlusion (MCAO), NBO treatment for 25 min and 150 min were studied. For the 90-min MCAO, NBO treatment for 55 min and 150 min were studied. Cerebral blood flow (CBF), apparent diffusion coefficients (ADC) and T2 MRI were acquired during occlusion prior to treatment, after reperfusion, and 48h after MCAO. The effects of NBO treatment on lesion volumes, and CBF, ADC and T2 of ischemic core, perfusion-diffusion mismatch and normal tissue were analyzed longitudinally. The major findings were: i) NBO treatment was effective in both groups of stroke severities, salvaging similar percentage of initial abnormal ADC tissue, and ii) NBO treatments continued after reperfusion were more beneficial than NBO treatment during occlusion alone for both MCAO groups. These findings underscore the importance of the effects of NBO duration and stroke severity on treatment outcomes. PMID- 26826012 TI - Arabidopsis thaliana gonidialess A/Zuotin related factors (GlsA/ZRF) are essential for maintenance of meristem integrity. AB - Observation of a differential expression pattern, including strong expression in meristematic tissue of an Agave tequilana GlsA/ZRF ortholog suggested an important role for this gene during bulbil formation and developmental changes in this species. In order to better understand this role, the two GlsA/ZFR orthologs present in the genome of Arabidopsis thaliana were functionally characterized by analyzing expression patterns, double mutant phenotypes, promoter-GUS fusions and expression of hormone related or meristem marker genes. Patterns of expression for A. thaliana show that GlsA/ZFR genes are strongly expressed in SAMs and RAMs in mature plants and developing embryos and double mutants showed multiple changes in morphology related to both SAM and RAM tissues. Typical double mutants showed stunted growth of aerial and root tissue, formation of multiple ectopic meristems and effects on cotyledons, leaves and flowers. The KNOX genes STM and BP were overexpressed in double mutants whereas CLV3, WUSCHEL and AS1 were repressed and lack of AtGlsA expression was also associated with changes in localization of auxin and cytokinin. These results suggest that GlsA/ZFR is an essential component of the machinery that maintains the integrity of SAM and RAM tissue and underline the potential to identify new genes or gene functions based on observations in non-model plants. PMID- 26826013 TI - Is insulin diluted when stored in water? AB - BACKGROUND: Insulin storage is a challenge in resource-poor countries. In Uganda, patients were noted to store insulin vials by submerging them in water. OBJECTIVE: To examine whether withdrawing insulin from a vial without adding air back causes a vacuum which allows water to enter the vial, resulting in insulin dilution. METHODS: Seven hundred units of insulin were withdrawn from forty 10 mL vials of 100 units/mL insulin [20 neutral protamine hagedorn (NPH), 20 regular]. In half, air was added back. The vials were weighed (baseline). Half of the vials (10 with added air, 10 without) were submerged in water for 24 h and then air dried for 24 h. Vials that were not submerged sat at room temperature for 48 h. All vials were weighed 48 h from baseline. RESULTS: Addition of air did not impact the change in weight after submersion (air added: -0.002 +/- 0.001 g or 0.2 +/- 0.1 unit; no air added: -0.003 +/- 0.000 g or -0.3 +/- 0 unit, p = 0.57). In a subset of vials in which an additional 240 units were withdrawn before submersion for another 24 h, there was still no difference in weight change in those vials with air added (p = 0.2). CONCLUSION: Withdrawing insulin from a vial without adding air did not result in uptake of water or dilution of insulin in the submerged vial, although it made drawing up the insulin easier. This study did not address the larger concern of bacterial contamination of the rubber stopper during water storage. PMID- 26826014 TI - Contribution of mechanical unloading to trabecular bone loss following non invasive knee injury in mice. AB - Development of osteoarthritis commonly involves degeneration of epiphyseal trabecular bone. In previous studies, we observed 30-44% loss of epiphyseal trabecular bone (BV/TV) from the distal femur within 1 week following non invasive knee injury in mice. Mechanical unloading (disuse) may contribute to this bone loss; however, it is unclear to what extent the injured limb is unloaded following injury, and whether disuse can fully account for the observed magnitude of bone loss. In this study, we investigated the contribution of mechanical unloading to trabecular bone changes observed following non-invasive knee injury in mice (female C57BL/6N). We investigated changes in gait during treadmill walking, and changes in voluntary activity level using Open Field analysis at 4, 14, 28, and 42 days post-injury. We also quantified epiphyseal trabecular bone using MUCT and weighed lower-limb muscles to quantify atrophy following knee injury in both ground control and hindlimb unloaded (HLU) mice. Gait analysis revealed a slightly altered stride pattern in the injured limb, with a decreased stance phase and increased swing phase. However, Open Field analysis revealed no differences in voluntary movement between injured and sham mice at any time point. Both knee injury and HLU resulted in comparable magnitudes of trabecular bone loss; however, HLU resulted in considerably more muscle loss than knee injury, suggesting another mechanism contributing to bone loss following injury. Altogether, these data suggest that mechanical unloading likely contributes to trabecular bone loss following non-invasive knee injury, but the magnitude of this bone loss cannot be fully explained by disuse. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1680-1687, 2016. PMID- 26826015 TI - Reducing the risk of transfusion-transmitted cytomegalovirus infection: a systematic review and meta-analysis. AB - BACKGROUND: Leukoreduced (LR) or cytomegalovirus (CMV)-seronegative cellular blood components are commonly used to reduce the risk of transfusion-transmitted CMV infection in high-risk patients. STUDY DESIGN AND METHODS: We performed a systematic review and meta-analysis to evaluate the evidence for the use of LR cellular blood components with or without concurrent CMV testing of donor units in patients undergoing chemotherapy or solid organ and hematopoietic stem cell transplantation, in pregnant women, in very-low-birthweight infants, and in patients with primary immunodeficiency. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from 1980 through February 2015. Studies were included if they had a comparison group. Two independent reviewers selected and appraised studies. Meta analysis was performed when appropriate. RESULTS: Of 457 studies screened, 11 were eligible. One study was excluded from the meta-analysis because the comparison performed differed significantly from the others. Meta-analysis of five studies that compared leukoreduction to transfusing CMV-untested blood components showed no significant difference in clinical CMV infection (relative risk [RR], 0.26; 95% confidence interval [CI], 0.04-1.57) or laboratory CMV infection (RR, 0.33; 95% CI, 0.08-1.37). Meta-analysis of three studies that compared leukoreduction to transfusing CMV-seronegative cellular components showed no significant difference in laboratory CMV infection (RR, 2.18; 95% CI, 0.96-4.98). Meta-analysis of two studies that compared adding CMV testing to leukoreduction (vs. leukoreduction alone) showed no significant difference in clinical or laboratory CMV infection. The certainty in estimates was low for all comparisons. CONCLUSION: At present, the scientific evidence does not favor a single strategy for reducing the risk of transfusion-related CMV infection in high-risk patients. PMID- 26826017 TI - HSPA6 is an ulcerative colitis susceptibility factor that is induced by cigarette smoke and protects intestinal epithelial cells by stabilizing anti-apoptotic Bcl XL. AB - BACKGROUND: Cigarette smoking ameliorates ulcerative colitis (UC) and aggravates Crohn's disease (CD). Cigarette smoke suppresses inflammation-induced apoptosis in intestinal epithelial cells (DLD-1), which may explain its protective effect in UC. Here, we performed transcriptome profiling of cigarette smoke extract (CSE)-exposed DLD-1 and Jurkat cells (T-lymphocytes) and related this to UC susceptibility genes with protective functions in the intestinal epithelium. METHODS: CSE-regulated genes in DLD-1 and Jurkat cells were identified by Illumina microarrays and compared to genes in UC susceptibility loci. Colon biopsies were analyzed by immunohistochemistry for cell-specific expression of HSPA6. CSE-induced gene expression was analyzed by Q-PCR, Western blotting and immunofluorescence microscopy. Protein (HSPA6/Bcl-XL) interactions were analyzed by immunoprecipitation. RESULTS: CSE changed the expression of 536 and 2560 genes in DLD-1 and Jurkat cells, respectively. The "response to unfolded protein" was one of the most significantly affected gene sets with prominent induction (20.3 fold) of heat shock protein A6 (HSPA6). Six CSE-induced genes in DLD-1 cells were located in UC-susceptibility loci, including HSPA6 (rs1801274). HSPA6 is highly expressed in the human colonic epithelium. CSE caused a dose-dependent strong (>100-fold at 30% CSE for 6h), but transient induction of HSPA6 mRNA and protein in DLD-1 cells. HSPA6 co-immune precipitated with anti-apoptotic Bcl-XL, protein levels of which were increased while mRNA levels were unchanged. CONCLUSIONS: HSPA6 is a cigarette smoke-induced UC-susceptibility gene. The HSPA6 risk locus is associated with decreased HSPA6 expression. HSPA6 provides epithelial protection by stabilizing anti-apoptotic Bcl-XL, thereby contributing to the beneficial effect of cigarette smoking in UC. PMID- 26826016 TI - Interplay between exercise and dietary fat modulates myelinogenesis in the central nervous system. AB - Here we show that the interplay between exercise training and dietary fat regulates myelinogenesis in the adult central nervous system. Mice consuming high fat with coordinate voluntary running wheel exercise for 7weeks showed increases in the abundance of the major myelin membrane proteins, proteolipid (PLP) and myelin basic protein (MBP), in the lumbosacral spinal cord. Expression of MBP and PLP RNA, as well that for Myrf1, a transcription factor driving oligodendrocyte differentiation were also differentially increased under each condition. Furthermore, expression of IGF-1 and its receptor IGF-1R, known to promote myelinogenesis, were also increased in the spinal cord in response to high dietary fat or exercise training. Parallel increases in AKT signaling, a pro myelination signaling intermediate activated by IGF-1, were also observed in the spinal cord of mice consuming high fat alone or in combination with exercise. Despite the pro-myelinogenic effects of high dietary fat in the context of exercise, high fat consumption in the setting of a sedentary lifestyle reduced OPCs and mature oligodendroglia. Whereas 7weeks of exercise training alone did not alter OPC or oligodendrocyte numbers, it did reverse reductions seen with high fat. Evidence is presented suggesting that the interplay between exercise and high dietary fat increase SIRT1, PGC-1alpha and antioxidant enzymes which may permit oligodendroglia to take advantage of diet and exercise-related increases in mitochondrial activity to yield increases in myelination despite higher levels of reactive oxygen species. PMID- 26826018 TI - EPAS1/HIF-2 alpha-mediated downregulation of tissue factor pathway inhibitor leads to a pro-thrombotic potential in endothelial cells. AB - Neovascularization and hemorrhaging are evident in advanced atherosclerotic plaques due to hypoxic conditions, and mediate the accumulation of metabolic substrates, inflammatory cells, lipids, and other blood born factors inside the plaque. Tissue factor (TF) pathway inhibitor (TFPI) is mainly expressed by endothelial cells and is the endogenous inhibitor of the coagulation activator TF, which together with the downstream product thrombin can drive plaque progression and atherogenesis. We aimed to investigate the effect of hypoxic conditions on endothelial cell expression and activity of TFPI and TF that are important in coagulation initiation. Hypoxia was induced in primary human umbilical vein endothelial cells using chemicals or 1% oxygen tension, and mRNA and protein expressions were measured using qRT-PCR, ELISA, and Western blot analysis. Microscopy of fluorescence-labeled cells was used to visualize cell associated TFPI. Cell-surface factor Xa (FXa) activity was measured using a two stage chromogenic substrate method. We found that hypoxia reduced the TFPI mRNA and protein levels and increased the TF mRNA expression in a dose-dependent manner. The effect on TFPI was apparent on all the protein pools of TFPI, i.e., secreted TFPI, cell-surface associated TFPI, and intracellular TFPI, and seemed to be dependent upon hypoxia inducible factor-2alpha (HIF-2alpha). An increase in FXa activity was also observed on the endothelial cell surface, reflecting an increase in pro-thrombotic potential of the cells. Our findings indicate that hypoxic conditions may enhance the pro-coagulant activity of endothelial cells, which may promote atherogenesis in addition to clinical events and thus the severity of atherosclerotic disorders. PMID- 26826019 TI - Tetrahydrobiopterin Role in human umbilical vein endothelial dysfunction in maternal supraphysiological hypercholesterolemia. AB - Maternal physiological hypercholesterolemia (MPH) allows a proper foetal development; however, maternal supraphysiological hypercholesterolemia (MSPH) associates with foetal endothelial dysfunction and early development of atherosclerosis. MSPH courses with reduced endothelium-dependent dilation of the human umbilical vein due to reduced endothelial nitric oxide synthase activity compared with MPH. Whether MSPH modifies the availability of the nitric oxide synthase cofactor tetrahydrobiopterin is unknown. We investigated whether MSPH associated lower umbilical vein vascular reactivity results from reduced bioavailability of tetrahydrobiopterin. Total cholesterol <7.2mmol/L was considered as maternal physiological hypercholesterolemia (n=72 women) and >=7.2mmol/L as MSPH (n=35 women). Umbilical veins rings were used for vascular reactivity assays (wire myography), and primary cultures of human umbilical vein endothelial cells (HUVECs) to measure nitric oxide synthase, GTP cyclohydrolase 1, and dihydrofolate reductase expression and activity, as well as tetrahydrobiopterin content. MSPH reduced the umbilical vein rings relaxation caused by calcitonine gene-related peptide, a phenomenon partially improved by incubation with sepiapterin. HUVECs from MSPH showed lower nitric oxide synthase activity (l-citrulline synthesis from l-arginine) without changes in its protein abundance, as well as reduced tetrahydrobiopterin level compared with MPH, a phenomenon reversed by incubation with sepiapterin. Expression and activity of GTP cyclohydrolase 1 was lower in MSPH, without changes in dihydrofolate reductase expression. MSPH is a pathophysiological condition reducing human umbilical vein reactivity due to lower bioavailability of tetrahydrobiopterin leading to lower NOS activity in the human umbilical vein endothelium. PMID- 26826020 TI - Building a Natural Language Processing Tool to Identify Patients With High Clinical Suspicion for Kawasaki Disease from Emergency Department Notes. AB - OBJECTIVE: Delayed diagnosis of Kawasaki disease (KD) may lead to serious cardiac complications. We sought to create and test the performance of a natural language processing (NLP) tool, the KD-NLP, in the identification of emergency department (ED) patients for whom the diagnosis of KD should be considered. METHODS: We developed an NLP tool that recognizes the KD diagnostic criteria based on standard clinical terms and medical word usage using 22 pediatric ED notes augmented by Unified Medical Language System vocabulary. With high suspicion for KD defined as fever and three or more KD clinical signs, KD-NLP was applied to 253 ED notes from children ultimately diagnosed with either KD or another febrile illness. We evaluated KD-NLP performance against ED notes manually reviewed by clinicians and compared the results to a simple keyword search. RESULTS: KD-NLP identified high-suspicion patients with a sensitivity of 93.6% and specificity of 77.5% compared to notes manually reviewed by clinicians. The tool outperformed a simple keyword search (sensitivity = 41.0%; specificity = 76.3%). CONCLUSIONS: KD NLP showed comparable performance to clinician manual chart review for identification of pediatric ED patients with a high suspicion for KD. This tool could be incorporated into the ED electronic health record system to alert providers to consider the diagnosis of KD. KD-NLP could serve as a model for decision support for other conditions in the ED. PMID- 26826021 TI - Fruit and Vegetables Consumption and Risk of Hypertension: A Meta-Analysis. AB - The association between fruit and vegetables (FVs) consumption and hypertension risk remains controversial. A systematic search was performed in PubMed and the Web of Science for relevant articles published in English or Chinese up to April 2015. A total of 25 studies with 334,468 patients (41,713 cases) were included in the present meta-analysis. When comparing the highest with the lowest consumption, the pooled relative risks of hypertension were 0.812 (95% confidence interval, 0.740-0.890) for FVs, 0.732 (95% confidence interval, 0.621-0.861) for fruit, and 0.970 (95% confidence interval, 0.918-1.024) for vegetables. A significantly inverse association between fruit consumption and hypertension risk was found in studies carried out in Asia (relative risk, 0.70; 95% confidence interval, 0.61-0.79). Influence analysis revealed that no individual study had an excessive influence on the pooled relative risks. The present meta-analysis indicates that FV consumption might be inversely associated with hypertension risk, which still needs to be confirmed by prospective cohort studies. PMID- 26826022 TI - Circadian system - A novel diagnostic and therapeutic target in Parkinson's disease? AB - The circadian system regulates biological rhythmicity in the human body. The role of the circadian system in neurological disorders is a theme that is attracting an increasing amount of interest from the scientific community. This has arisen, in part, from emerging evidence that disorders such as Parkinson's disease (PD) are multifactorial with many features exhibiting diurnal fluctuations, thereby suggestive of circadian involvement. Although the importance of fluctuating motor and nonmotor manifestations in PD have been well acknowledged, the role of the circadian system has received little attention until recently. It is proposed that intervening with circadian function provides a novel research avenue down which new strategies for improving symptomatic treatment and slowing of the progressive degenerative process can be approached to lessen the burden of PD. In this article we review the literature describing existing circadian research in PD and its experimental models. PMID- 26826024 TI - Phloretin-induced cytoprotective effects on mammalian cells: A mechanistic view and future directions. AB - Phloretin (C15 H14 O5 ), a dihydrochalcone flavonoid, is mainly found in fruit, leaves, and roots of apple tree. Phloretin exerts antioxidant, anti-inflammatory, and anti-tumor activities in mammalian cells through mechanisms that have been partially elucidated throughout the years. Phloretin bioavailability is well known in humans, but still remains to be better studied in experimental animals, such as mouse and rat. The focus of the present review is to gather information regarding the mechanisms involved in the phloretin-elicited effects in different in vitro and in vivo experimental models. Several manuscripts were analyzed and data raised by authors were described and discussed here in a mechanistic manner. Comparisons between the effects elicited by phloretin and phloridzin were made whenever possible, as well as with other polyphenols, clarifying questions about the use of phloretin as a potential therapeutic agent. Toxicological aspects associated to phloretin exposure were also discussed here. Furthermore, a special section containing future directions was created as a suggestive guide towards the elucidation of phloretin-related actions in mammalian cells and tissues. PMID- 26826023 TI - Anionic fluoroquinolones as antibacterials against biofilm-producing Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa is a common biofilm-forming bacterial pathogen implicated in diseases of the lungs. The extracellular polymeric substances (EPS) of respiratory Pseudomonas biofilms are largely comprised of anionic molecules such as rhamnolipids and alginate that promote a mucoid phenotype. In this Letter, we examine the ability of negatively-charged fluoroquinolones to transverse the EPS and inhibit the growth of mucoid P. aeruginosa. Anionic fluoroquinolones were further compared with standard antibiotics via a novel microdiffusion assay to evaluate drug penetration through pseudomonal alginate and respiratory mucus from a patient with cystic fibrosis. PMID- 26826025 TI - Panobinostat: A Review in Relapsed or Refractory Multiple Myeloma. AB - Oral panobinostat (Farydak(r)), a potent nonselective histone deacetylase inhibitor, is approved in several countries for use in combination with bortezomib and dexamethasone in patients with multiple myeloma (MM) [USA] or relapsed and/or refractory MM (EU) who have received at least two prior treatment regimens, including bortezomib and an immunomodulatory drug (IMiD). In a pivotal phase III trial (PANORAMA 1) in patients with relapsed or relapsed and refractory MM who had received one to three previous lines of therapy, progression-free survival (PFS) was significantly prolonged with panobinostat plus bortezomib and dexamethasone compared with placebo plus bortezomib and dexamethasone. The significantly favourable effect of panobinostat- versus placebo-based treatment on PFS was also observed in a subgroup analysis of patients who had previously received an IMiD, bortezomib plus an IMiD, or at least two lines of treatment including bortezomib and an IMiD. Panobinostat plus bortezomib and dexamethasone had a generally manageable tolerability profile, with the most frequent grade 3-4 adverse events being myelosuppression, diarrhoea, asthenia or fatigue, peripheral neuropathy and pneumonia. Thus, panobinostat, in combination with bortezomib and dexamethasone, is a useful addition to the available treatment options for patients with relapsed or refractory MM. PMID- 26826026 TI - [Fractures of the proximal interphalangeal joint: Diagnostic and operative therapy options]. AB - Joint fractures of the fingers often entail operative interventions in contrast to extra-articular fractures. These types of fracture are inclined to dislocate in addition to the actual fracture. The proximal interphalangeal (PIP) joint in particular often shows comminuted fractures due to the long leverage of the finger and a relatively small diameter of the joint. The clinical examination, X ray diagnostics and if necessary computed tomography allow the classification into stable and unstable fractures. Unstable fractures must be treated by surgical reduction and fixation. A multitude of operative techniques are available for these mostly complicated fractures. The foremost goal is a stable osteosynthesis of the fracture with repositioning of the dislocation, which enables early physiotherapy in order to prevent tendon adhesion and contracture. This article presents the different types of PIP joint fractures, their specific surgical treatment and postoperative treatment regimens. PMID- 26826027 TI - [Ankle impingement. Indications and arthroscopic therapy]. AB - Ankle impingement syndromes are one of the most frequent chronic and posttraumatic pathologies of the ankle joint. Anterior and posterior impingement result from the abutting of anatomical structures leading to pain and limitation in the range of motion of the ankle joint. Ankle impingement can be classified based on the localization or the underlying cause. Besides chronic ankle pain, further symptoms are movement and load-dependent swelling of the ankle joint and limitations in dorsiflexion and plantar flexion. The clinical symptoms and physical examination play an essential role in diagnosing soft tissue impingement, whereas various imaging techniques are important for the diagnostics of bony impingement. From a therapeutic perspective, conservative treatment should be initially attempted. If non-operative treatment fails, arthroscopic resection and debridement of the underlying cause is nowadays the standard method of surgical treatment. With a current complication rate of approximately 3 % ankle arthroscopy is a safe operative method, which is associated with a high postoperative rate of patient satisfaction and significant relief of symptoms. PMID- 26826028 TI - Treatment of full-thickness cartilage lesions and early OA using large condyle resurfacing prosthesis: UniCAP((r)). AB - PURPOSE: The UniCAP ((r)) implant for femoral resurfacing treatment of large cartilage lesions and early OA was introduced in 2006. The outcome of the present study is from a prospective cohort study of 64 patients, followed 2 years clinically and 7 years for revisions. METHODS: From 2009 to 2013, 64 patients were treated with femoral resurfacing using the UniCAP implant. Indication for treatment with UniCAP implant was symptomatic huge cartilage lesion or early OA at the femoral condyle demonstrated by MRI or arthroscopy, which was ICRS grades 3-4 and more than 4 cm(2). There were 28 males and 36 females with a median age of 51 (range 35-65) years. Patients were followed for 2 years clinically with Knee Society subjective outcome scores (KSS), pain scores and radiographic evaluations and for 7 years with complications and reoperations. RESULTS: At 2 years, the follow-up mean KSS improved from 49 (6.9) to 88 (17.1), the mean KSS function score improved from 46 (8.0) to 90 (17.1), and the mean Pain score improved from 7.4 (0.5) to 2.3 (1.4). 47 % of the implants were revised within 7 years to arthroplasty due to the progression of cartilage lesions, progressing of osteoarthritis or increased knee pain. The reoperation rate did not show any significant difference between females and males. The Kaplan-Meier survival rate was 50 % at 7 years, no difference among females and males. CONCLUSION: The present study demonstrated an improved subjective outcome and reduced pain after femoral resurfacing using the UniCAP ((r)) implant in a relatively large cohort of patients with symptomatic large cartilage lesions or early OA. A 47 % reoperation rate with conversion to arthroplasty was found. The femoral resurfacing implantation can be a temporary treatment for large cartilage lesions or early OA that is expected to develop into osteoarthritis. For younger patients who are ineligible for arthroplasty treatment, this implant can offer a temporary solution. LEVEL OF EVIDENCE: IV. PMID- 26826029 TI - Impact of Treatment and Insurance on Socioeconomic Disparities in Survival after Adolescent and Young Adult Hodgkin Lymphoma: A Population-Based Study. AB - BACKGROUND: Previous studies documented racial/ethnic and socioeconomic disparities in survival after Hodgkin lymphoma among adolescents and young adults (AYA), but did not consider the influence of combined-modality treatment and health insurance. METHODS: Data for 9,353 AYA patients ages 15 to 39 years when diagnosed with Hodgkin lymphoma during 1988 to 2011 were obtained from the California Cancer Registry. Using multivariate Cox proportional hazards regression, we examined the impact of sociodemographic characteristics [race/ethnicity, neighborhood socioeconomic status (SES), and health insurance], initial combined-modality treatment, and subsequent cancers on survival. RESULTS: Over the 24-year study period, we observed improvements in Hodgkin lymphoma specific survival by diagnostic period and differences in survival by race/ethnicity, neighborhood SES, and health insurance for a subset of more recently diagnosed patients (2001-2011). In multivariable analyses, Hodgkin lymphoma-specific survival was worse for Blacks than Whites with early-stage [HR: 1.68; 95% confidence interval (CI): 1.14-2.49] and late-stage disease (HR: 1.68; 95% CI, 1.17-2.41) and for Hispanics than Whites with late-stage disease (HR: 1.58; 95% CI, 1.22-2.04). AYAs diagnosed with early-stage disease experienced worse survival if they also resided in lower SES neighborhoods (HR: 2.06; 95% CI, 1.59-2.68). Furthermore, more recently diagnosed AYAs with public health insurance or who were uninsured experienced worse Hodgkin lymphoma-specific survival (HR: 2.08; 95% CI, 1.52-2.84). CONCLUSION: Our findings identify several subgroups of Hodgkin lymphoma patients at higher risk for Hodgkin lymphoma mortality. IMPACT: Identifying and reducing barriers to recommended treatment and surveillance in these AYAs at much higher risk of mortality is essential to ameliorating these survival disparities. PMID- 26826030 TI - Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice. AB - Testis specific protein, Y-encoded-like 2 (TSPYL2) regulates the expression of genes encoding glutamate receptors. Glutamate pathology is implicated in neurodevelopmental conditions such as autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and schizophrenia. In line with this, a microduplication incorporating the TSPYL2 locus has been reported in people with ADHD. However, the role of Tspyl2 remains unclear. Therefore here we used a Tspyl2 loss-of-function mouse model to directly examine how this gene impacts upon behavior and brain anatomy. We hypothesized that Tspyl2 knockout (KO) would precipitate a phenotype relevant to neurodevelopmental conditions. In line with this prediction, we found that Tspyl2 KO mice were marginally more active, had significantly impaired prepulse inhibition, and were significantly more 'sensitive' to the dopamine agonist amphetamine. In addition, the lateral ventricles were significantly smaller in KO mice. These findings suggest that disrupting Tspyl2 gene expression leads to behavioral and brain morphological alterations that mirror a number of neurodevelopmental psychiatric traits. PMID- 26826031 TI - Effects of Maternal Smoking during Pregnancy on Offspring Externalizing Problems: Contextual Effects in a Sample of Female Twins. AB - Studies of maternal smoking during pregnancy (MSDP) suggest increased risk for cognitive impairment and psychiatric outcomes. However, it is uncertain whether these associations are the direct result of MSDP or related to confounding familial variables associated with MSDP. The current study employed propensity score analysis to examine the effects of MSDP on offspring EXT using data from a large sample of 979 unrelated mothers. Logistic regression models were used to determine the propensity that the offspring of these mothers were likely to be exposed to MSDP [i.e., smoked during only the first trimester (MSDP-EARLY[E]) or smoked throughout their pregnancy (MSDP-THROUGHOUT[T])] given known familial confounders. Analyses focused on the effect of MSDP-E/T on the EXT behavior in offspring of these mothers (N = 1616) were conducted across the distribution of liability for MSDP-E/T and at different levels of risk for MSDP-E/T. MSDP-E/T was associated with offspring EXT problems, but the effects were partly confounded by the familial liability for MSDP. Further, the observed effects were not consistent across all levels of the MSDP risk distribution. These findings suggest a direct association between MSDP and offspring EXT behaviors, and that varied associations observed across studies may be the result of differences in the level of familial confounders that also have an effect on offspring EXT. PMID- 26826032 TI - Design Features of Explicit Values Clarification Methods: A Systematic Review. AB - BACKGROUND: Values clarification is a recommended element of patient decision aids. Many different values clarification methods exist, but there is little evidence synthesis available to guide design decisions. PURPOSE: To describe practices in the field of explicit values clarification methods according to a taxonomy of design features. DATA SOURCES: MEDLINE, all EBM Reviews, CINAHL, EMBASE, Google Scholar, manual search of reference lists, and expert contacts. STUDY SELECTION: Articles were included if they described 1 or more explicit values clarification methods. DATA EXTRACTION: We extracted data about decisions addressed; use of theories, frameworks, and guidelines; and 12 design features. DATA SYNTHESIS: We identified 110 articles describing 98 explicit values clarification methods. Most of these addressed decisions in cancer or reproductive health, and half addressed a decision between just 2 options. Most used neither theory nor guidelines to structure their design. "Pros and cons" was the most common type of values clarification method. Most methods did not allow users to add their own concerns. Few methods explicitly presented tradeoffs inherent in the decision, supported an iterative process of values exploration, or showed how different options aligned with users' values. LIMITATIONS: Study selection criteria and choice of elements for the taxonomy may have excluded values clarification methods or design features. CONCLUSIONS: Explicit values clarification methods have diverse designs but can be systematically cataloged within the structure of a taxonomy. Developers of values clarification methods should carefully consider each of the design features in this taxonomy and publish adequate descriptions of their designs. More research is needed to study the effects of different design features. PMID- 26826033 TI - Evaluation of a Dust Control for a Small Slab-Riding Dowel Drill for Concrete Pavement. AB - PURPOSE: To assess the effectiveness of local exhaust ventilation to control respirable crystalline silica exposures to acceptable levels during concrete dowel drilling. APPROACH: Personal breathing zone samples for respirable dust and crystalline silica were collected while laborers drilled holes 3.5 cm diameter by 36 cm deep in a concrete slab using a single-drill slab-riding dowel drill equipped with local exhaust ventilation. Data were collected on air flow, weather, and productivity. RESULTS: All respirable dust samples were below the 90 ug detection limit which, when combined with the largest sample volume, resulted in a minimum detectable concentration of 0.31 mg m(-3). This occurred in a 32-min sample collected when 27 holes were drilled. Quartz was only detected in one air sample; 0.09 mg m(-3) of quartz was found on an 8-min sample collected during a drill maintenance task. The minimum detectable concentration for quartz in personal air samples collected while drilling was performed was 0.02 mg m(-3). The average number of holes drilled during each drilling sample was 23. Over the course of the 2-day study, air flow measured at the dust collector decreased from 2.2 to 1.7 m(3) s(-1). CONCLUSIONS: The dust control performed well under the conditions of this test. The initial duct velocity with a clean filter was sufficient to prevent settling, but gradually fell below the recommended value to prevent dust from settling in the duct. The practice of raising the drill between each hole may have prevented the dust from settling in the duct. A slightly higher flow rate and an improved duct design would prevent settling without regard to the position of the drill. PMID- 26826034 TI - The mitochondrial pyruvate carrier in health and disease: To carry or not to carry? AB - Mitochondria play a key role in energy metabolism, hosting the machinery for oxidative phosphorylation, the most efficient cellular pathway for generating ATP. A major checkpoint in this process is the transport of pyruvate produced by cytosolic glycolysis into the mitochondrial matrix, which is accomplished by the recently identified mitochondrial pyruvate carrier (MPC). As the gatekeeper for pyruvate entry into mitochondria, the MPC is thought to be of fundamental importance in establishing the metabolic programming of a cell. This is especially relevant in the context of the aerobic glycolysis, also known as the Warburg effect, which is a hallmark in many types of cancer, and MPC loss of function promotes cancer growth. Moreover, mitochondrial pyruvate uptake is needed for efficient hepatic gluconeogenesis and the regulation of blood glucose levels. In this review we discuss recent advances in our knowledge of the MPC, and we argue that it may offer a promising target in diseases like cancer and type 2 diabetes. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. PMID- 26826035 TI - The VDAC channel: Molecular basis for selectivity. AB - The voltage dependent anion-selective channel, VDAC, is the major permeability pathway by which molecules and ion cross the mitochondrial outer membrane. This pathway has evolved to optimize the flow of these substances and to control this flow by a gating process that is influenced by a variety of factors including transmembrane voltage. The permeation pathway formed through the membrane by VDAC is complex. Small ion flow is primarily influenced by the charged surface of the inner walls of the channel. Channel closure changes this landscape resulting in a change from a channel that favors anions to one that favors cations. Molecular ions interact more intimately with the inner walls of the channel and are selected by their 3-dimensional structure, not merely by their size and charge. Molecular ions typically found in cells are greatly favored over those that are not. For these larger structures the channel may form a low-energy translocation path that complements the structure of the permeant. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. PMID- 26826036 TI - Activation of autophagy by globular adiponectin is required for muscle differentiation. AB - Regulated autophagy is a critical component for a healthy skeletal muscle mass, such that dysregulation of the autophagic processes correlates with severe myopathies. Thus, defining the biological molecules involved in the autophagic processes within skeletal muscle is of great importance. Here we demonstrate that globular adiponectin (gAd) activates autophagy in skeletal muscle myoblasts via an AMPK-dependent mechanism. Activation of autophagy through gAd promotes myoblast survival and apoptosis inhibition during serum starvation and the gAd activated autophagy orchestrates the myogenic properties of the hormone. Consistent with this conclusion, inhibition of gAd-activated autophagy by both a pharmacological (chloroquine) or siRNA approach greatly inhibited muscle differentiation, as demonstrated by reductions in myosin heavy chain expression and myotube formation. Further support for the role of adiponectin in autophagy comes from the skeletal muscles of adiponectin KO mice which display decreased LC3 II expression and a myopathic phenotype (heterogeneous fiber sizes, numerous central nuclei). Overall, these findings demonstrate that gAd activates autophagy in myoblasts and that gAd-activated autophagy drives the myogenic properties of this hormone. PMID- 26826037 TI - Midwife-led care before, during and after childbirth - the best option for most women and babies. PMID- 26826038 TI - How can midwives promote a normal birth and a positive birth experience? The experience of first-time Norwegian mothers. AB - OBJECTIVE: The purpose of this study is to gain a deeper understanding of the experience of first-time mothers regarding how the midwife may promote a normal birth and a positive birth experience. METHODS: A qualitative approach was chosen for data collection, and the data presented are based on in-depth interviews. Twelve healthy, first-time Norwegian mothers, aged 22-34, who had experienced a normal and positive childbirth were interviewed five to six weeks after giving birth. The transcribed interviews were analysed with the help of systematic text condensation. RESULTS: The findings included two main themes: "To be seen as an individual" and "Health-promoting perspective". The experience of being cared for by a midwife who provides presence is vital for the woman to be seen as an individual. When the midwife has a health-promoting perspective, she can more easily assist the woman in developing inner strength and coping strategies. CONCLUSION: Midwives have a pivotal role in helping to promote a normal birth and positive birth experience. The women consider the midwife's attitude and behaviour as essential for their ability to feel safe and cared for. The midwife's individualized and motivating approach promotes the women's inner strength and belief in their own capability to handle the birth. Based on this salutogenic view, the midwife must focus on the woman's resources in order to promote good health during the childbearing process. PMID- 26826039 TI - Viewing the unborn child - pregnant women's expectations, attitudes and experiences regarding fetal ultrasound examination. AB - OBJECTIVE: To gain a deeper understanding of pregnant women's expectations, attitudes and experiences regarding ultrasound examination during pregnancy. METHODS: In-depth interviews were conducted with eight pregnant Norwegian women prior to their 18-week scan. The data were analyzed through systematic text condensation. RESULTS: The analysis generated three main themes: (1) I want to know if everything is fine, (2) Viewing the unborn child, (3) Holistic care. The women had a strong wish for ultrasound scanning and medical knowledge about their "baby" was their first priority interest. Visualizing the "baby" represented a strong emotional dimension for the parents-to-be and initiated the bonding process and the planning of a new life. The women wanted to be empowered and approached in a holistic way, where dialogic communication was needed. CONCLUSION: The women wanted medical knowledge about the fetal health. They considered the examination a visual experience together with their partner. The scan provided a personification of and an attachment to the fetus. This experience was the first step in the planning of a new life. The women had ambivalent feelings related to the ultrasound examination and they highlighted the importance of holistic care, where the sharing of information happens on an individual basis. PMID- 26826040 TI - Use of emergency contraception in Nigeria: An exploration of related factors among sexually active female university students. AB - OBJECTIVE: Unsafe abortions account for nearly one-third of maternal deaths among young people. Women who have an induced abortion are usually literate and less than 30 years old; usually undergraduates with unintended pregnancies. Many of these pregnancies could have been prevented by contraception. The aim of this study was to determine the correlates of uptake of emergency contraception among university students. METHODS: A cross-sectional study was conducted among 1328 sexually active, never married female university students. Self-administered questionnaire was used to assess knowledge, perception and practice of emergency contraception. Multivariate logistic regression was used to identify the predictors of emergency contraception. RESULTS: Majority of the participants were aware of emergency contraception (72.6%), had good knowledge (56.0%), and had the perception that it is effective (74.6%) and easy to use (72.4%). The main sources of information about emergency contraception were friends (32.9%) and the media (20.0%). About 52.0% of the participants had unprotected sex in the preceding six months, while 718 (54.1%) had ever used emergency contraception. The main sources of the commodities were sexual partners (46.2%) and medicine stores (35.4%). The uptake of emergency contraception was predicted by being <=19 years (AOR = 3.193), rural dwelling (AOR = 4.247), perceptions that it is effective (AOR = 2.229E11) and easy to use (AOR = 6.680E8). CONCLUSION: Use of contraception among sexually active female Nigerian university students is predicted by the perception about its effectiveness and ease of use. Sexual and reproductive health programmes should focus on improving knowledge and addressing misconception in order to improve perception about emergency contraception. PMID- 26826041 TI - Healthcare students' knowledge and opinions about the Argentinean abortion law. AB - OBJECTIVE: Abortion is legally restricted in Argentina. Although this law is almost 100 years old, most women who meet the criteria for legal abortion are not informed of or offered this possibility within the healthcare system. Healthcare students' knowledge and opinions on abortion may influence their future practice. They may deny a woman with an unwanted pregnancy a practice to which she is legally entitled, resulting in an unsafe abortion. This study assessed knowledge and personal opinions on the abortion law among first year healthcare students in order to design adequate educational strategies. STUDY DESIGN: In this descriptive, analytical, cross-sectional study, structured self-administered questionnaires were administered to 781 first year medical, nursing, midwifery, and other healthcare students from the Faculty of Medicine, University of Buenos Aires from 2011 to 2013. Data were recorded anonymously in SPSS 20. Student samples were adjusted for gender and fields of study using the University statistics. RESULTS: Of the students, 48.8% did not know the current regulations. Most of the students thought abortion was legally restricted and failed to recognize the circumstances in which it is allowed. Over 75% of the students were pro-abortion, especially those with sexual experience. CONCLUSION: Students lack sound knowledge on the abortion law that may affect their personal lives and influence their future professional practice. It is crucial that medical schools include sexual and reproductive health issues in their curricula in order to ensure better quality healthcare services in the future. IMPLICATIONS: In Argentina, approximately 400,000 abortions are performed every year, many under unsafe conditions, resulting in one third of the maternal deaths for the past decade. High quality sexual and reproductive healthcare services are a key strategy to improve adolescents' and women's health, thereby lowering maternal mortality. PMID- 26826042 TI - Swedish women's interest in models of midwifery care - Time to consider the system? A prospective longitudinal survey. AB - BACKGROUND: Sweden has an international reputation for offering high quality maternity care, although models that provide continuity of care are rare. The aim was to explore women's interest in models of care such as continuity with the same midwife, homebirth and birth center care. METHODS: A prospective longitudinal survey where 758 women's interest in models such as having the same midwife throughout antenatal, intrapartum and postpartum care, homebirth with a known midwife, and birth center care were investigated. RESULTS: Approximately 50% wanted continuity of care with the same midwife throughout pregnancy, birth and the postpartum period. Few participants were interested in birth center care or home birth. Fear of giving birth was associated with a preference for continuity with midwife. CONCLUSIONS: Continuity with the same midwife could be of certain importance to women with childbirth fear. Models that offer continuity of care with one or two midwives are safe, cost-effective and enhance the chance of having a normal birth, a positive birth experience and possibly reduce fear of birth. The evidence is now overwhelming that all women should have maternity care delivered in this way. PMID- 26826043 TI - Family sense of coherence and family and marital functioning across the perinatal period. AB - BACKGROUND: A family sense of coherence is central to successfully coping with family stressors and facilitates positive adaptation. Little is known about the implications of family sense of coherence for family adaptation during the transition to parenthood. OBJECTIVE: The objective of this study was to examine the role of family sense of coherence in family and marital functioning during the perinatal period. METHODS: The study used a longitudinal design. A convenience sample of 202 Chinese childbearing couples completed the Medical Outcomes Study Family and Marital Functioning Measures and Family Sense of Coherence Scale during pregnancy, at 6 weeks and at 6 months postpartum. RESULTS: The results showed that the couples experienced a substantial decline in family and marital functioning postpartum and that a strong family sense of coherence was associated with better family and marital functioning in the perinatal period. The levels of family sense of coherence for both mothers and fathers were fairly stable across the perinatal period. CONCLUSION: The study provides evidence that family sense of coherence plays a significant role in promoting family and marital functioning during the transition to parenthood. PMID- 26826044 TI - The effect of counselling on nausea and vomiting in pregnancy in Turkey. AB - OBJECTIVES: The aim of this study was to assess the effects of follow-up counselling on the duration and severity of nausea and vomiting in pregnant women. STUDY DESIGN: This study is quasi-experimental and included 62 pregnant women with nausea and vomiting. The group that received counselling was considered to be the experimental group, and the group that received a standard outpatient clinic service was the control group. Data were collected with a demographic data form, that is, the Nausea and Vomiting in Pregnancy Instrument and Pregnancy Unique Quantification of Emesis and Nausea. Significance tests of the differences between two mean values, the Mann-Whitney U test and survival analyses were used to test the hypotheses. RESULTS: In pregnant women with mild or moderate nausea and vomiting, nausea and vomiting terminated in a significantly shorter time in the experimental group than in the control group (p <0.001), but this difference was not significant for pregnant women with severe nausea and vomiting (p > 0.05). In addition, the number of weekly telephone follow-ups in the experimental group was significantly smaller (p <0.001). CONCLUSION: Counselling effectively reduced the duration and severity of mild or moderate nausea and vomiting during pregnancy. However, it did not affect the duration of severe nausea and vomiting during pregnancy. PMID- 26826045 TI - HPV vaccine introduction in Rwanda: Impacts on the broader health system. AB - OBJECTIVES: Rwanda was the first country in Africa to introduce the human papillomavirus (HPV) vaccine. This was achieved through multi-year school-based campaigns. Our study evaluated the impact of the HPV vaccine introduction on the country's immunisation programme and health system. METHODS: Thirty key informants were interviewed at national and district levels, and in participating schools. Twenty-seven health facilities completed a questionnaire exploring the effects of the new vaccine introduction on six health system building blocks, as defined by the World Health Organization. Routine service activity data were collected during a 90-day period around the introduction. RESULTS: Routine vaccination activities were not disrupted during the delivery, likely due to a strong Expanded Program on Immunization, appropriate planning and a well resourced operation. Opportunities were seized to co-deliver other interventions targeted at children and adolescents, such as health promotion. Collaboration with the Ministry of Education was strengthened at national level. Although there were some temporary increases in staff workload, no major negative effects were reported. CONCLUSION: Despite its delivery through school-based campaigns, the HPV vaccine integrated well into the immunisation programme and health system. The introduction had no major negative effects. Some opportunities were seized to expand services and collaborations. PMID- 26826046 TI - Quality of intra-partum care at a university hospital in Nepal: A prospective cross-sectional survey. AB - OBJECTIVE: To investigate the quality of intra-partum care provided to women with an expected normal birth at a university hospital in Nepal. METHODS: A prospective cross-sectional study was conducted during three weeks in November 2013. Nurses at the labor ward collected data from 292 consecutive births. Of these, 164 women of low risk were expected to have a normal birth and were included in the study; 107 (65%) were nulliparous. The self-administered questionnaire covered maternal characteristics, previous pregnancies and births, current pregnancy, labor and birth. Nine items assessed care management, five of which comprised the Bologna score with a total possible score of 5: presence of a companion, use of partograph, non-use of augmentation, non-supine position, and skin-to-skin contact. RESULTS: The women were assisted by physicians (56%), nurses (42%) or students under supervision (2%). All were in good health after birth. Two had a postpartum hemorrhage exceeding 500 ml and 49% had an episiotomy. Apgar score in all neonates was >= 7 at five minutes. Mean Bologna score was 1.43 (variance 0-3). CONCLUSIONS: The management of care in normal birth could be improved in the studied setting, and there is a need for more research to support such improvement. PMID- 26826047 TI - Norwegian midwives' perceptions of empowerment. AB - INTRODUCTION: Midwives are educated to care for women during pregnancy, birth and the postnatal period. For midwives to be able to fulfill their professional role they need to be empowered to do so. AIM OF THE STUDY: To investigate Norwegian midwives' perception of empowerment in practice. METHOD: A cross-sectional study. In September 2014, a random sample of 1500 midwives was sent a questionnaire, which included the Perception of Empowerment in Midwifery Practice Scale (PEMS). Of 1458 eligible midwives, 595 (41%) completed the PEMS. Exploratory factor analyses and comparative analyses were done. RESULTS: Exploratory factor analyses identified three factors (subscales): Supportive management, Autonomous professional role, and Equipped for practice. Midwives working in a hospital setting scored significantly lower on the factors Supportive management and Autonomous professional role compared to midwives not working in a hospital setting (p < 0.001). Midwives with extra/special responsibilities scored higher than those without (p < 0.001) on the same two factors. Midwives working at units with <2500 births scored significantly higher on all three factors compared to midwives working at units with >=2500 births (p < 0.001). CONCLUSION: The PEMS showed that Norwegian midwives' perception of empowerment at work differed according to midwives' education, role at work, duration of work experience, working situation and environment. This study supports the psychometric qualities of the PEMS. PMID- 26826048 TI - "A challenge" - healthcare professionals' experiences when meeting women with symptoms that might indicate endometriosis. AB - OBJECTIVE: The aim of the study was to identify and describe the experiences of healthcare professionals when meeting women with symptoms that might indicate endometriosis. METHODS: Semi-structured interviews were conducted with 10 gynecologists, six general practitioners and nine midwives working at one university hospital, one central hospital, one private gynecology clinic and five healthcare centers in south-east Sweden. The interviews were recorded and transcribed verbatim and analyzed using qualitative conventional content analysis. RESULTS: Three clusters were identified: the corroborating encounter, the normal variation of menstruation cycles, and the suspicion of endometriosis. The healthcare professionals tried to make a corroborating encounter by acknowledging the woman, taking time to listen, and giving an explanation for the problems. Healthcare professionals had different ways to determine what was normal as regards menstrual pain, ovulation pain and dyspareunia. They also needed to have the competence to act and react when the symptoms indicated endometriosis. CONCLUSIONS: Meeting women with symptoms that might indicate endometriosis is challenging and demands a certain level of competence from healthcare professionals. Sometimes the symptoms are camouflaged as "normal" menstruation pain, making it hard to satisfy the needs of this patient group. PMID- 26826049 TI - Breastfeeding, pregnant, and non-breastfeeding nor pregnant women's food consumption: A matched within-household analysis in India. AB - OBJECTIVE: Promoting breastfeeding is major maternal and child health goal in India. It is unclear whether mothers receive additional food needed to support healthy breastfeeding. METHODS: Using the latest National Family and Health Survey (2005-2006), we applied multilevel linear regression models to document correlates of nutrition for (n = 20,764) breastfeeding women. We then compared consumption of pulses, eggs, meat, fish, dairy, fruit, and vegetables across a sample of breastfeeding, non-breastfeeding/pregnant (NBP), and pregnant women (n = 3,409) matched within households and five-year age bands. We tested whether breastfeeding women had greater advantages in the 18 high-focus states of India's National Rural Health Mission (NRHM). RESULTS: Vegetarianism, caste, and religion were the strongest predictors of breastfeeding women's nutrition. Breastfeeding women had no nutritional advantage compared to NBP women, and were disadvantaged in their consumption of milk (b = -0.14) in low-focus states. Pregnant women were similarly disadvantaged in their consumption of milk in low-focus states (b = 0.32), but consumed vegetables more frequently (b = 0.12) than NBP women in high focus states. CONCLUSIONS: Breastfeeding women do not receive nutritional advantages compared to NBP women. Targeted effort is needed to assess and improve nutritional adequacy for breastfeeding Indian women. PMID- 26826050 TI - Association between tribal status and spacing contraceptive use in rural Maharashtra, India. AB - This study examines associations between tribal status and spacing contraception use (SCU) in rural Maharashtra, India. Cross-sectional analyses were conducted on baseline survey data from non-sterilized married couples (n = 867) participating in the CHARM family planning evaluation study. Participants were aged 18-30 years and 67.6% were tribal; 27.7% reported current SCU. Crude regression analyses indicated that tribals were less likely to use contraception (AOR = 0.04, 95% CI = 0.29, 0.54); this association was lost after adjusting for education, higher parity and desire for pregnancy, factors associated with tribal status. Findings suggest that lower SCU among tribals is driven by social vulnerabilities and higher fertility preferences. PMID- 26826051 TI - Concordance of handheld reflectance confocal microscopy (RCM) with histopathology in the diagnosis of lentigo maligna (LM): A prospective study. AB - BACKGROUND: Reflectance confocal microscopy (RCM) provides real-time noninvasive imaging of cell structure and may be useful in diagnosing lentigo maligna (LM). Few studies have compared performance of RCM with histopathology in diagnosing LM, and specific features influencing RCM interpretation are not well described. OBJECTIVE: We sought to determine concordance rate between RCM and histopathology in the evaluation of suspected LM and to identify factors that may obscure diagnosis. METHODS: We designed a prospective study involving 17 participants seen for evaluation at a large tertiary referral center. Cases included primary lesions and possible recurrent and/or previously treated lesions. A total of 63 clinically equivocal sites were assessed by RCM and histopathology. RESULTS: RCM and histopathology interpretations were concordant in 56 of 63 sites (89%). There were no false-negative and 7 false-positive results using RCM (sensitivity 100%, specificity 71%, positive predictive value 85%, negative predictive value 100%). Features suggestive of LM in the false-positive group included the presence of numerous hyperreflectile large cells at the dermoepidermal junction and follicular localization of these cells. LIMITATIONS: A larger test set is needed to more reliably distinguish LM from benign lesions using RCM and to improve specificity. CONCLUSION: RCM shows excellent sensitivity for detecting LM although features of benign macules on a background of actinically damaged skin can obscure diagnosis and limit its specificity. PMID- 26826052 TI - Agronomic nitrogen-use efficiency of rice can be increased by driving OsNRT2.1 expression with the OsNAR2.1 promoter. AB - The importance of the nitrate (NO3-) transporter for yield and nitrogen-use efficiency (NUE) in rice was previously demonstrated using map-based cloning. In this study, we enhanced the expression of the OsNRT2.1 gene, which encodes a high affinity NO3- transporter, using a ubiquitin (Ubi) promoter and the NO3- inducible promoter of the OsNAR2.1 gene to drive OsNRT2.1 expression in transgenic rice plants. Transgenic lines expressing pUbi:OsNRT2.1 or pOsNAR2.1:OsNRT2.1 constructs exhibited the increased total biomass including yields of approximately 21% and 38% compared with wild-type (WT) plants. The agricultural NUE (ANUE) of the pUbi:OsNRT2.1 lines decreased to 83% of that of the WT plants, while the ANUE of the pOsNAR2.1:OsNRT2.1 lines increased to 128% of that of the WT plants. The dry matter transfer into grain decreased by 68% in the pUbi:OsNRT2.1 lines and increased by 46% in the pOsNAR2.1:OsNRT2.1 lines relative to the WT. The expression of OsNRT2.1 in shoot and grain showed that Ubi enhanced OsNRT2.1 expression by 7.5-fold averagely and OsNAR2.1 promoters increased by about 80% higher than the WT. Interestingly, we found that the OsNAR2.1 was expressed higher in all the organs of pUbi:OsNRT2.1 lines; however, for pOsNAR2.1:OsNRT2.1 lines, OsNAR2.1 expression was only increased in root, leaf sheaths and internodes. We show that increased expression of OsNRT2.1, especially driven by OsNAR2.1 promoter, can improve the yield and NUE in rice. PMID- 26826053 TI - Effect of low-dose X-ray irradiation and Ti particles on the osseointegration of prosthetic. AB - Low-dose irradiation (LDI) exhibits a positive effect on osteoblasts and inhibitory effect of inflammation. Here, we test the hypothesis that LDI can promote osseointegration and inhibit the inflammatory membrane formation in the presence of titanium (Ti) particles. Endotoxin-free titanium particles were injected into rabbit, prior to the insertion of a Ti6-Al-4-V sticks pre-coated with hydroxyapatite. Two days after operation, both distal femurs of the animal were exposed to 0.5 Gy X-ray irradiation. All ani-mals were euthanized 8 weeks after the operation. The PINP concentration was determined at day 0, 2, 4, and 8 weeks after operation. Trabecular morphology around the implants 8 weeks after operation was assessed using micro-CT, then the maximum push out force of simples was assessed using biomechanics test. Five samples in each group were chosen for bone histomorphology study without decalcification 8 weeks after operation. The results confirmed that the LDI can significantly improve ingrowth of bone into the prosthetic interface and stability of the prosthesis when there was no wear particles. Although promotion effects for bone formation induced by LDI can be counteracted by wear particles, LDI can significantly inhibit the interface membrane formation around the implant induced by wear particles. Based on these results, we conclude that LDI may be useful for enhancing the stability of prosthesis when there are no wear particles and for inhibiting the interface membrane formation during the early stage of aseptic loosening in the presence of wear particles. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1688-1696, 2016. PMID- 26826054 TI - A brief motivational interview with action and coping planning components enhances motivational autonomy among volunteer blood donors. AB - BACKGROUND: In contrast to standard donor retention strategies (e.g., mailings, phone calls, text messages), we developed a brief telephone interview, based on motivational interviewing principles, that encourages blood donors to reflect upon their unique motivators and barriers for giving. This study examined the effect of this motivational interview, combined with action and coping plan components, on blood donor motivations. STUDY DESIGN AND METHODS: The design was to randomly assign blood donors to receive either a telephone-delivered motivational interview with action and coping plan components or a control call approximately 6 weeks after their most recent donation. Participants completed a series of surveys related to donation motivation approximately 3 weeks before telephone contact (precall baseline) and then repeated these surveys approximately 1 week after telephone contact (postcall). RESULTS: The sample was 63% female, included a majority (52.6%) of first-time blood donors, and had a mean age of 30.0 years (SD, 11.7 years). A series of analyses of variance revealed that, relative to controls (n = 244), donors in the motivational interview group (n = 254) had significantly larger increases in motivational autonomy (p = 0.001), affective attitude (p = 0.004), self-efficacy (p = 0.03), anticipated regret (p = 0.001), and intention (p = < 0.001), as well as larger decreases in donation anxiety (p = 0.01), from precall baseline to postcall assessment. CONCLUSION: This study supports motivational interviewing with action and coping planning as a novel strategy to promote key contributors to donor motivation. PMID- 26826055 TI - Cost analysis of the Hemodialysis Reliable Outflow (HeRO) Graft compared to the tunneled dialysis catheter. AB - BACKGROUND: In end-stage renal disease patients with central venous obstruction, who have limited vascular access options, the Hemodialysis Reliable Outflow (HeRO) Graft is a new alternative with a lower incidence of complications and longer effective device life compared to tunneled dialysis catheters (TDCs). We undertook an economic analysis of introducing the HeRO Graft in the UK. METHODS: A 1-year cost-consequence decision analytic model was developed comparing management with the HeRO Graft to TDCs from the perspective of the National Health Service in England. The model comprises four 3-month cycles during which the vascular access option either remains functional for hemodialysis or fails, patients can experience access-related infection and device thrombosis, and they can also accrue associated costs. Clinical input data were sourced from published studies and unit cost data from National Health Service 2014-15 Reference Costs. RESULTS: In the base case, a 100-patient cohort managed with the HeRO Graft experienced 6 fewer failed devices, 53 fewer access-related infections, and 67 fewer device thromboses compared to patients managed with TDCs. Although the initial device and placement costs for the HeRO Graft are greater than those for TDCs, savings from the lower incidence of device complications and longer effective device patency reduces these costs. Overall net annual costs are L2600 for each HeRO Graft-managed patient compared to TDC-managed patients. If the National Health Service were to reimburse hemodialysis at a uniform rate regardless of the type of vascular access, net 1-year savings of L1200 per patient are estimated for individuals managed with the HeRO Graft. CONCLUSIONS: The base case results showed a marginal net positive cost associated with vascular access with the HeRO Graft compared with TDCs for the incremental clinical benefit of reductions in patency failures, device-related thrombosis, and access-related infection events in a patient population with limited options for dialysis vascular access. PMID- 26826056 TI - Resection of recurrent neck cancer with carotid artery replacement. AB - OBJECTIVE: The management of patients with recurrent neck cancer invading the carotid artery is controversial. The purpose of this study was to evaluate overall survival rate, primary patency of vascular reconstructions, and quality adjusted life-years (QALYs) after en bloc resection of the carotid artery and tumor with in-line polytetrafluoroethylene (PTFE) carotid grafting, followed by radiotherapy. METHODS: From 2000 to 2014, 31 consecutive patients with recurrent neck cancer invading the carotid artery underwent en bloc resection and simultaneous carotid artery reconstruction with a PTFE graft, which was associated in 18 cases with a myocutaneous flap. The primary tumor was a squamous cell carcinoma of the larynx in 17 patients and of the hypopharynx in 7, an undifferentiated carcinoma of unknown origin in 4, and an anaplastic carcinoma of the thyroid in 3. All of the patients underwent postoperative radiotherapy (50-70 Gy), and 10 of them also underwent chemotherapy (doxorubicin and cisplatin). RESULTS: None of the patients died or sustained a stroke during the first 30 days after the index procedure. Postoperative morbidity consisted of 6 transitory dysphagias, 3 vocal cord palsies, 2 wound dehiscences, 1 transitory mandibular claudication, and 1 partial myocutaneous flap necrosis. No graft infection occurred during follow-up. Fifteen patients (48%) died from metastatic cancer during a mean follow-up of 45.4 months (range, 8-175 months). None of the patients showed evidence of local recurrence, stroke, or thrombosis of the carotid reconstruction. The 5-year survival rate was 49 +/- 10%. The overall number of QALYs was 3.12 (95% confidence interval, 1.87-4.37) with a significant difference between patients without metastasis at the time of redo surgery (n = 26; QALYs, 3.74) and those with metastasis (n = 5; QALYs, 0.56; P = .005). QALYs were also significantly improved in patients with cancer of the larynx (n = 17; QALYs, 4.69) compared to patients presenting with other types of tumors (n = 14; QALYs, 1.29; P = .032). CONCLUSIONS: Aggressive en bloc resection of recurrent neck cancer with PTFE grafting can be curative in patients without metastases at the time of redo surgery. In this subset of patients, extensive neck surgery with carotid artery replacement can lead to excellent local control of the disease with improved quality of survival. PMID- 26826057 TI - Age at detection of abdominal aortic aneurysms in siblings of patients with abdominal aortic aneurysms. AB - OBJECTIVE: Few countries offer organized screening of siblings of patients with abdominal aortic aneurysms (AAAs), although a hereditary trait is well known to exist. Male relatives, but not female, are invited within the population-based screening programs for elderly men in Sweden. Evidence regarding the optimal age to screen siblings is scarce. The aim of this study was to describe the age at detection in siblings found with AAAs. METHODS: All patients treated for AAAs in two Swedish counties were screened for siblings. Consenting siblings aged 80 and younger were examined (N = 529) with ultrasound and were interviewed per protocol. RESULTS: In the cohort of 529 siblings to AAA patients, 53 siblings were diagnosed with AAAs (sisters 16/276 [5.8%] and brothers 37/253 [14.6%]). The prevalence of AAAs in the siblings 65 years of age or younger was 16/207 (7.7%). One-third of the siblings found with AAAs were young (16/53 [30%]). Among the young siblings with AAAs, 8/16 (50%) had an aneurysm larger than 50 mm or were already surgically treated. The prevalence of AAAs in siblings older than 65 years of age was 37/322 (12%). CONCLUSIONS: The AAA prevalence in this sibling cohort is strikingly high compared to the prevalence in the population (in Sweden, 1.4%-2.2% in 65-year-old men). The young ages among diagnosed siblings reinforce that male siblings of AAA patients should be screened before age 65 (before the population-based program) and that structured programs for female siblings are called for. PMID- 26826058 TI - Percutaneous removal using Perclose ProGlide closure devices versus surgical removal for weaning after percutaneous cannulation for venoarterial extracorporeal membrane oxygenation. AB - OBJECTIVE: The removal of arterial cannulas using a Perclose device (Abbott Vascular, Clonmel, Tipperary, Ireland) has not been reported in patients undergoing venoarterial extracorporeal membrane oxygenation (ECMO). We investigated the procedural outcomes and complications of percutaneous device closure vs surgical repair for hemostatic control of the arterial access site in weaning from venoarterial ECMO. METHODS: Between September 2012 and December 2014, 115 patients with ECMO weaned by percutaneous or surgical access were enrolled. The percutaneous technique used two ProGlide devices (Abbott Vascular) by direct puncture of an arterial cannula at the time of weaning off ECMO. The primary outcomes were composite complications of open repair at the insertion site, limb ischemia after removal of the arterial cannula, removal site infection, pseudoaneurysm, distal part embolization, and 10 minutes or more manual compression at the weaning site. RESULTS: The percutaneous technique was performed on 56 patients, and the surgical exposure technique was performed on 59. Technical success was not significantly different between the percutaneous and surgical groups (85.7% vs 86.4%; P = 1.0) although the procedure duration (17.15 +/- 9.38 minutes vs 64.33 +/- 31.67 minutes; P < .001) was shorter in the percutaneous access group. A composite of procedure-related complications and length of stay in the intensive care unit after weaning was not significantly different between groups (17.9% vs 28.8%; P = .19 and 16.82 +/- 38.53 days vs 19.69 +/- 21.40 days; P = .62). CONCLUSIONS: Percutaneous access using two Perclose ProGlide devices was a feasible and safe strategy for weaning from ECMO. PMID- 26826059 TI - Emergency Medicine Resources Within the Clinical Translational Science Institutes: A Cross-sectional Study. AB - BACKGROUND: The Clinical and Translational Science Award (CTSA) program aims to strengthen and support translational research by accelerating the process of translating laboratory discoveries into treatments for patients, training a new generation of clinical and translational researchers, and engaging communities in clinical research efforts. Yet, little is known about how emergency care researchers have interacted with and utilized the resources of academic institutions with CTSAs. OBJECTIVES: The purpose of this survey was to describe how emergency care researchers use local CTSA resources, to ascertain what proportion of CTSA consortium members have active emergency care research (ECR) programs, and to solicit participation in a national CTSA-associated emergency care translational research network. METHODS: This study was a survey of all emergency departments affiliated with a CTSA. RESULTS: Of the 65 CTSA consortium members, three had no ECR program and we obtained responses from 46 of the remaining 62 (74% response rate). The interactions with and resources used by emergency care researchers varied widely. Methodology and biostatistics support was most frequently accessed (77%), followed closely by education and training programs (60%). Several ECR programs (76%) had submitted for funding through CTSAs, with 71% receiving awards. Most CTSA consortium members had an active ECR infrastructure: 21 (46%) had 24/7 availability to recruit and screen for research, and 21 (46%) had less than 24/7 research recruitment. A number of emergency care research programs participated in National Institutes of Health research networks with the Neurological Emergencies Treatment Trials network most highly represented with 23 (59%) sites. Most ECR programs (96%) were interested in participating in a CTSA-based emergency care translational research network. CONCLUSIONS: Despite little initial involvement in development of the CTSA program, there has been moderate interaction between CTSAs and emergency care. There is considerable interest in participating in a CTSA consortium-based emergency care translational research network. PMID- 26826060 TI - Mesenchymal stem cells and alginate microcarriers for craniofacial bone tissue engineering: A review. AB - Craniofacial bone is a complex structure with an intricate anatomical and physiological architecture. The defects that exist in this region therefore require a precise control of osteogenesis in their reconstruction. Unlike traditional surgical intervention, tissue engineering techniques mediate bone development with limited postoperative risk and cost. Alginate stands as the premier polymer in bone repair because of its mild ionotropic gelation and excellent biocompatibility, biodegradability, and injectability. Alginate microcarriers are candidates of choice to mediate cells and accommodate into 3-D environment. Several studies reported the use of alginate microcarriers for delivering cells, drugs, and growth factors. This review will explore the potential use of alginate microcarrier for stem cell systems and its application in craniofacial bone tissue engineering. PMID- 26826063 TI - The Development and Evaluation of Countermeasures to Tactile Change Blindness. AB - OBJECTIVE: The goal of the present study was to develop and empirically evaluate three countermeasures to tactile change blindness (where a tactile signal is missed in the presence of a tactile transient). Each of these countermeasures relates to a different cognitive step involved in successful change detection. BACKGROUND: To date, change blindness has been studied primarily in vision, but there is limited empirical evidence that the tactile modality may also be subject to this phenomenon. Change blindness raises concerns regarding the robustness of tactile and multimodal interfaces. METHOD: Three countermeasures to tactile change blindness were evaluated in the context of a highly demanding monitoring task. One countermeasure was proactive (alerting the participant to a possible change before it occurred) whereas the other two were adaptive (triggered after the change upon an observed miss). Performance and subjective data were collected. RESULTS: Compared to the baseline condition, all countermeasures improved intramodal tactile change detection. Adaptive measures resulted in the highest detection rates, specifically when signal gradation was employed (i.e., when the intensity of the tactile signal was increased after a miss was observed). CONCLUSION: Adaptive displays can be used to counter the effects of change blindness and ensure that tactile information is reliably detected. Increasing the tactile intensity after a missed change appears most promising and was the preferred countermeasure. APPLICATION: The findings from this study can inform the design of interfaces employing the tactile modality to support monitoring and attention management in data-rich domains. PMID- 26826064 TI - Inhibition of succinate dehydrogenase sensitizes cyclin E-driven ovarian cancer to CDK inhibition. AB - AIM: High-grade serous ovarian cancer (HGS-OvCa) is characterized by widespread CCNE1 amplification. Current treatments lack specificity to target Cyclin E driven OvCa. METHODS: By in silico analysis of the TCGA OvCa dataset we searched association between genes involved in glucose metabolism and cell cycle control. Metabolic shift was studied in Cyclin E-driven OvCa cells treated with CDK inhibition (CDKi). Genetic and pharmaceutical inhibition of succinate dehydrogenase (SDH) was tested in combination with CDKi. RESULTS: OvCa patients with CCNE1 amplification could be divided by concomitant SDHA amplification. A2780 OvCa cells were similar to the Cyclin E-driven and SDHA neutral genotype. CDKi in A2780 cells using Dinaciclib resulted in compensatory enhancement of tricarboxylicacid cycle (TCA) cycle activity. Combined blockade of CDK and SDH, both genetically and pharmaceutically, showed synergy and resulted in inhibited proliferation, migration, invasion and migration in A2780 cells. The combined inhibition did not further alter cell cycle population, but induced apoptosis of A2780 cells. CONCLUSION: Cyclin E-driven OvCa cells appeared addicted to glucose metabolism via TCA. Combined CDKi with modalities targeting TCA, like SDHA inhibition showed promising effects for this genotype. PMID- 26826065 TI - Vitreous levels of vascular endothelial growth factor-B in proliferative diabetic retinopathy. PMID- 26826066 TI - Pulmonary Kaposi's Sarcoma and Its Complications in the HAART Era: A Contemporary Case-Based Review. AB - The early years of the acquired immunodeficiency syndrome (AIDS) epidemic introduced the global medical community to Kaposi's sarcoma (KS), a heretofore seldom encountered angiosarcomatous neoplasm associated with human herpesvirus-8. At that time, clinicians treating these KS patients were routinely exposed to the pulmonary manifestations of this malignancy, including characteristic airway lesions, peribronchovascular opacities, and the typically hemorrhagic pleural effusions. They also witnessed uncommon complications of pulmonary KS such as chylous effusions, diffuse alveolar hemorrhage, and immune reconstitution inflammatory syndrome. Since the advent of highly active antiretroviral therapy, the incidence of KS has steadily declined and with that so has clinician familiarity with this disease. Herein, we present four KS cases recently encountered at our institution that illustrate both typical manifestations of pulmonary KS as well as its thoracic complications. The case descriptions are followed by a review of these clinical entities with the aim of restoring awareness among frontline physicians of what is now a rare but not quite extinct AIDS-defining neoplasm. PMID- 26826067 TI - Management of dystonia in Europe: a survey of the European network for the study of the dystonia syndromes. AB - BACKGROUND AND PURPOSE: Dystonia is difficult to recognize due to its large phenomenological complexity. Thus, the use of experts in dystonia is essential for better recognition and management of dystonia syndromes (DS). Our aim was to document managing strategies, facilities and expertise available in various European countries in order to identify which measures should be implemented to improve the management of DS. METHODS: A survey was conducted, funded by the Cooperation in Science and Technology, via the management committee of the European network for the study of DS, which is formed from representatives of the 24 countries involved. RESULTS: Lack of specific training in dystonia by general neurologists, general practitioners as well as other allied health professionals was universal in all countries surveyed. Genetic testing for rare dystonia mutations is not readily available in a significant number of countries and neurophysiological studies are difficult to perform due to a lack of experts in this field of movement disorders. Tetrabenazine is only readily available for treatment of dystonia in half of the surveyed countries. Deep brain stimulation is available in three-quarters of the countries, but other surgical procedures are only available in one-quarter of countries. CONCLUSIONS: Internationally, collaboration in training, advanced diagnosis, treatment and research of DS and, locally, in each country the creation of multidisciplinary teams for the management of dystonia patients could provide the basis for improving all aspects of dystonia management across Europe. PMID- 26826068 TI - Reducing Implicit Gender Leadership Bias in Academic Medicine With an Educational Intervention. AB - PURPOSE: One challenge academic health centers face is to advance female faculty to leadership positions and retain them there in numbers equal to men, especially given the equal representation of women and men among graduates of medicine and biological sciences over the last 10 years. The purpose of this study is to investigate the explicit and implicit biases favoring men as leaders, among both men and women faculty, and to assess whether these attitudes change following an educational intervention. METHOD: The authors used a standardized, 20-minute educational intervention to educate faculty about implicit biases and strategies for overcoming them. Next, they assessed the effect of this intervention. From March 2012 through April 2013, 281 faculty members participated in the intervention across 13 of 18 clinical departments. RESULTS: The study assessed faculty members' perceptions of bias as well as their explicit and implicit attitudes toward gender and leadership. Results indicated that the intervention significantly changed all faculty members' perceptions of bias (P < .05 across all eight measures). Although, as expected, explicit biases did not change following the intervention, the intervention did have a small but significant positive effect on the implicit biases surrounding women and leadership of all participants regardless of age or gender (P = .008). CONCLUSIONS: These results suggest that providing education on bias and strategies for reducing it can serve as an important step toward reducing gender bias in academic medicine and, ultimately, promoting institutional change, specifically the promoting of women to higher ranks. PMID- 26826069 TI - Does Time Pressure Have a Negative Effect on Diagnostic Accuracy? AB - PURPOSE: Studies suggest time pressure has negative effects on physicians' working conditions and may lead to suboptimal patient care and medical errors. Experimental evidence supporting this is lacking, however. This study investigated the effect of time pressure on diagnostic accuracy. METHOD: In 2013, senior internal medicine residents at three hospitals in Saudi Arabia were divided randomly into two groups: a time-pressure condition and a control condition without time pressure. Both groups diagnosed eight written clinical cases presented on computers. In the time-pressure condition, after completing each case, participants received information that they were behind schedule. Response time was recorded, and diagnostic accuracy was scored. RESULTS: The 23 participants in the time-pressure condition spent significantly less time diagnosing the cases (mean = 96.00 seconds) than the 19 control participants (mean = 151.97 seconds) (P < .001). Participants under time pressure had a significantly lower diagnostic accuracy score (mean = 0.33; 95% CI, 0.23-0.43) than participants without time pressure (mean = 0.51; 95% CI, 0.42-0.60) (F[1, 41] = 6.90, P = .012, eta = 0.15). This suggests participants in the time pressure condition made on average 37% more errors than control participants. CONCLUSIONS: Time pressure has a negative impact on diagnostic performance. The authors propose that the effect of time pressure on diagnostic accuracy is moderated by both the case difficulty level and the physician's level of experience. Post hoc analyses demonstrated that time pressure affects diagnostic accuracy only if cases are not too difficult and physicians' expertise level is intermediate. PMID- 26826070 TI - Creating a Cadre of Fellowship-Trained Medical Educators: A Qualitative Study of Faculty Development Program Leaders' Perspectives and Advice. AB - PURPOSE: Well-trained educators fill essential roles across the medical education continuum. Some medical schools offer programs for existing faculty to enhance teaching and scholarship. No standard postgraduate training model exists for residency graduates to attain competency as faculty members before their first academic appointment. The objective of this study is to inform the development of postgraduate medical education fellowships by exploring perceptions of educational leaders who direct well-established faculty development programs. METHOD: The authors undertook a qualitative study, using purposeful sampling to recruit participants and a constant comparative approach to identify themes. They conducted semistructured telephone interviews with directors of faculty development fellowships using an interpretivist/constructivist paradigm (November 2013). Questions addressed curricular and fiscal structure, perceived benefits and challenges, and advice for starting a postgraduate fellowship. RESULTS: Directors reported institutional and participant benefits, notably the creation of a community of educators and pool of potential leaders. Curricular offerings focused on learning theory, teaching, assessment, leadership, and scholarship. Funding and protected time were challenges. Advice for new program directors included evaluating best practices, defining locally relevant goals; garnering sufficient, stable financial support; and rallying leaders' endorsement. CONCLUSIONS: Medical education fellowships cultivate leaders and communities of trained educators but require participants to balance faculty responsibilities with professional development. Advice of current directors can inform the development of postgraduate programs modeled after accredited clinical specialty fellowships. Programs with the support of strategic partners, financial stability, and well-defined goals may allow new faculty to begin their careers with existing competency in medical education skills. PMID- 26826071 TI - Establishing an Ambulatory Medicine Quality and Safety Oversight Structure: Leveraging the Fractal Model. AB - PROBLEM: Academic health systems face challenges in the governance and oversight of quality and safety efforts across their organizations. Ambulatory practices, which are growing in number, size, and complexity, face particular challenges in these areas. APPROACH: In February 2014, leaders at Johns Hopkins Medicine (JHM) implemented a governance, oversight, and accountability structure for quality and safety efforts across JHM ambulatory practices. This model was based on the fractal approach, which balances independence and interdependence and provides horizontal and vertical support. It set expectations of accountability at all levels from the Board of Trustees to frontline staff and featured a cascading structure that reached all units and ambulatory practices. This model leveraged an Ambulatory Quality Council led by a physician and nurse dyad to provide the infrastructure to share best practices, continuously improve, and define accountable local leaders. OUTCOMES: This model was incorporated into the quality and safety infrastructure across JHM. Improved outcomes in the domains of patient safety/risk reduction, externally reported quality measures, patient care/experience, and value have been demonstrated. An additional benefit was an improvement in Medicaid value-based purchasing metrics, which are linked to several million dollars of revenue. NEXT STEPS: As this model matures, it will serve as a mechanism to align quality standards and programs across regional, national, and international partners and to provide a clear quality structure as new practices join the health system. Future efforts will link this model to JHM's academic mission, enhancing education to address Accreditation Council for Graduate Medical Education core competencies. PMID- 26826072 TI - Predicting Peer Nominations Among Medical Students: A Social Network Approach. AB - PURPOSE: Minimal attention has been paid to what factors may predict peer nomination or how peer nominations might exhibit a clustering effect. Focusing on the homophily principle that "birds of a feather flock together," and using a social network analysis approach, the authors investigated how certain student- and/or school-based factors might predict the likelihood of peer nomination, and the clusters, if any, that occur among those nominations. METHOD: In 2013, the Jefferson Longitudinal Study of Medical Education included a special instrument to evaluate peer nominations. A total of 211 (81%) of 260 graduating medical students from the Sidney Kimmel Medical College responded to the peer nomination question. Data were analyzed using a relational contingency table and an ANOVA density model. RESULTS: Although peer nominations did not cluster around gender, age, or class rank, those students within an accelerated program, as well as those entering certain specialties, were more likely to nominate each other. The authors suggest that clerkships in certain specialties, as well as the accelerated program, may provide structured opportunities for students to connect and integrate, and that these opportunities may have an impact on peer nomination. The findings suggest that social network analysis is a useful approach to examine various aspects of peer nomination processes. CONCLUSIONS: The authors discuss implications regarding harnessing social cohesion within clinical clerkships, the possible development of siloed departmental identity and in-group favoritism, and future research possibilities. PMID- 26826073 TI - The Road to Excellence for Primary Care Resident Teaching Clinics. AB - Primary care residency programs and their associated primary care clinics face challenges in their goal to simultaneously provide a good education for tomorrow's doctors and excellent care for today's patients. A team from the Center for Excellence in Primary Care at the University of California, San Francisco, conducted site visits to 23 family medicine, internal medicine, and pediatric residency teaching clinics. The authors found that a number of programs have transformed themselves with respect to engaged leadership, resident scheduling, continuity of care for patients and residents, team-based care, and resident engagement in practice improvement. In this Commentary, the authors highlight the features of transforming programs that are melding inspiring resident education with excellent patient care. The authors propose a model, the 10 + 3 Building Blocks of Primary Care Teaching Clinics, to illustrate the themes that characterize transforming primary care residency programs. PMID- 26826074 TI - Ethics and Regulatory Challenges and Opportunities in Patient-Centered Comparative Effectiveness Research. AB - The Affordable Care Act includes provisions for the conduct of large-scale, patient-centered comparative effectiveness research. Such efforts aim toward the laudable moral goal of having evidence to improve health care decision making. Nevertheless, these pragmatic clinical research efforts that typically pose minimal incremental risk and are enmeshed in routine care settings perhaps surprisingly encounter an array of ethics and regulatory challenges and opportunities for academic health centers. An emphasis on patient-centeredness forces an examination of the appropriateness of traditional methods used to protect the rights, interests, and welfare of participants. At the same time, meaningful collaboration with patients throughout the research process also necessitates ensuring that novel approaches to research (including recruitment and consent) entail necessary protections regarding such issues as privacy. As the scientific and logistical aspects of this research are being developed, substantial attention is being focused on the accompanying ethics and regulatory issues that have emerged, which should help to facilitate ethically appropriate research in a variety of contexts. PMID- 26826078 TI - Two-tube multiplex real-time reverse transcription PCR to detect six human coronaviruses. PMID- 26826079 TI - Using the inverse Poisson distribution to calculate multiplicity of infection and viral replication by a high-throughput fluorescent imaging system. PMID- 26826080 TI - Risk factors for severity and mortality in patients with MERS-CoV: Analysis of publicly available data from Saudi Arabia. PMID- 26826081 TI - Influence of bone mineral density measurement on fracture risk assessment tool(r) scores in postmenopausal Indian women. AB - AIM: Fracture risk assessment tool(r) calculations can be performed with or without addition of bone mineral density; however, the impact of this addition on fracture risk assessment tool(r) scores has not been studied in Indian women. Given the limited availability and high cost of bone mineral density testing in India, it is important to know the influence of bone mineral density on fracture risk assessment tool(r) scores in Indian women. Therefore, our aim was to assess the contribution of bone mineral density in fracture risk assessment tool(r) outcome in Indian women. METHODS: Apparently healthy postmenopausal Indian women (n = 506), aged 40-72 years, without clinical risk factors for bone disease, were retrospectively selected, and their fracture risk assessment tool(r) scores calculated with and without bone mineral density were compared. RESULTS: Based on WHO criteria, 30% women were osteoporotic, 42.9% were osteopenic and 27.1% had normal bone mineral density. Fracture risk assessment tool(r) scores for risk of both major osteoporotic fracture and hip fracture significantly increased on including bone mineral density (P < 0.0001). When criteria of National Osteoporosis Foundation, US was applied number of participants eligible for medical therapy increased upon inclusion of bone mineral density, (for major osteoporotic fracture risk number of women eligible without bone mineral density was 0 and with bone mineral density was 1, P > 0.05, whereas, for hip fracture risk number of women eligible without bone mineral density was 2 and with bone mineral density was 17, P < 0.0001). CONCLUSION: Until the establishment of country-specific medication intervention thresholds, bone mineral density should be included while calculating fracture risk assessment tool(r) scores in Indian women. PMID- 26826082 TI - Feasibility of unilateral parathyroidectomy in patients with primary hyperparathyroidism and negative or discordant localization studies. AB - The purpose of this study was to examine the feasibility of unilateral parathyroidectomy in patients with primary hyperparathyroidism and negative or discordant localization studies. We included in our study 72 patients with preoperative diagnosis of primary hyperparathyroidism who had negative or discordant preoperative studies. In 66 patients, studies were discordant while in six were both negative. In 40 (55.6 %) patients initial approach was a bilateral exploration. In 32 cases (44.4 %) initial surgery was a unilateral exploration: in 26 conservative approach was successful, in six mini-invasive surgery failed and a bilateral exploration was necessary due to IOPTH negative test (five cases) or to the impossibility to find a pathological gland during exploration (one case). Intra-operative PTH test showed a sensitivity of 93.2 %, a specificity of 92.3 %, and an accuracy of 93.1 %. Multiple gland disease was found in 8 (11.1 %) patients (two double adenoma and six multiple gland hyperplasia). Mean operative time was lower in unilateral exploration group (87.9 +/- 43.8 min). Comparing unilateral surgery in negative or discordant studies with 77 consecutive patients who underwent focused surgery with positive and concordant studies, conversion to bilateral exploration rate was statistically significantly higher in the first group (15.6 %). We believe that unilateral parathyroidectomy can be safely performed also in patients with discordant localization studies with a high cure rate; in these cases, however, the use of intra-operative PTH is absolutely necessary. We suggest the need for referral of these patients to high-volume medical centers for thyroid and parathyroid surgery. PMID- 26826083 TI - Surgical treatment of high stage endometrial cancer: current perspectives. AB - Endometrial cancer is now the most common gynecologic malignancy. We investigate on new scientific evidences in endometrial cancer, particularly underlined updates in advanced endometrial cancer. Early stage endometrial cancer is the most frequent presentation; however, advanced endometrial cancer that occurs in 3 13 % of cases has bad prognosis. There are two types of endometrial cancer different in molecular pattern, therapeutic strategy and prognosis. Type I endometrial cancers develop in an environment of unopposed estrogen and often arise out of endometrial hyperplasia, characterized by mutations in the PTEN gene, K-ras, and microsatellite instability inception. Type II cancer is not an estrogen-related cancer, occurs predominantly in postmenopausal women, shows typical mutations in p53 and HER2/neu and has a poor prognosis. Preoperative characterization of the type's disease is an essential step for a right diagnosis and treatment. All patients should undergo to surgical staging, except those who are inoperable, according to FIGO recommendation. Surgical debulking, neoadjuvant chemotherapy and interval debulking can be strategy options. PMID- 26826084 TI - Functional outcomes of transmetatarsal amputation in the diabetic foot: timing of revascularization, wound healing and ambulatory status. AB - Transmetatarsal amputation (TMA) is an effective surgical approach to treat forefoot infection and gangrene in diabetic patients. However, a high rate of complications and failure to heal require reamputation in a large number of cases. We analysed the outcomes of TMA to define the role of revascularization, wound healing and ambulatory status. From January 2008 to January 2013, 218 diabetic patients with foot infection and gangrene, submitted to TMA associated to revascularization were followed until healing, amputation or death. Revascularization was done in 202 (92 %) cases. In 16 (7 %) no revascularization was required. The TMA was closed in 135 (62 %) and left open in 83 (38 %) cases. The reamputation rate was 34 % and major amputation 12.6 % at 1-year follow-up. Patient following ranged 2-30 months with a mean of 15 months. The functional outcomes, living at home and ambulation outdoors, were 60 and 36 % at hospital discharge after TMA, 81 and 77 % at 1-year follow-up. TMA associated to revascularization can provide an effective limb salvage and functional results in diabetic patients with forefoot tissue loss and infection. PMID- 26826085 TI - Commentary. PMID- 26826086 TI - Image fusion and navigation platforms for percutaneous image-guided interventions. AB - Image-guided interventional procedures, particularly image guided biopsy and ablation, serve an important role in the care of the oncology patient. The need for tumor genomic and proteomic profiling, early tumor response assessment and confirmation of early recurrence are common scenarios that may necessitate successful biopsies of targets, including those that are small, anatomically unfavorable or inconspicuous. As image-guided ablation is increasingly incorporated into interventional oncology practice, similar obstacles are posed for the ablation of technically challenging tumor targets. Navigation tools, including image fusion and device tracking, can enable abdominal interventionalists to more accurately target challenging biopsy and ablation targets. Image fusion technologies enable multimodality fusion and real-time co displays of US, CT, MRI, and PET/CT data, with navigational technologies including electromagnetic tracking, robotic, cone beam CT, optical, and laser guidance of interventional devices. Image fusion and navigational platform technology is reviewed in this article, including the results of studies implementing their use for interventional procedures. Pre-clinical and clinical experiences to date suggest these technologies have the potential to reduce procedure risk, time, and radiation dose to both the patient and the operator, with a valuable role to play for complex image-guided interventions. PMID- 26826087 TI - Incidence of bleeding complications after percutaneous core needle biopsy in hypertensive patients and comparison to normotensive patients. AB - PURPOSE: To retrospectively determine the rate of major bleeding complications after solid organ or lung biopsy in patients with hypertension and compare to the rates of bleeding in normotensive patients. MATERIALS AND METHODS: Following IRB approval, retrospective review of all solid organ and lung biopsies performed at our institution between June 1st, 2013 and October 31st, 2015 was performed. Hypertension was defined as a maximum observed systolic blood pressure of 160 mmHg or greater and/or diastolic blood pressure of 90 mmHg or greater at the time of the biopsy procedure. Bleeding complications were defined using the Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) established by the National Cancer Institute. RESULTS: 4756 total biopsies in 3876 unique patients (median age 60, 57% male) were included. 1488 (31.3%) of these biopsies were performed in hypertensive patients. Fifteen major hemorrhages (CTCAE grade 3 or higher) occurred (0.32%). There were no deaths. There was no significant association between hypertension and major bleeding. The incidence of bleeding in hypertensive patients was 0.40% (6/1488), which was not statistically different than the incidence in normotensive patients (9/3268, 0.28%, p = 0.496). For the subgroup of native renal parenchymal biopsies, the rate of bleeding was slightly higher in hypertensive patients (3/213, 1.4% vs. 1/355, 0.28% in normotensive patients) but remained low, and the difference was not statistically significant (p = 0.188). CONCLUSION: The overall incidence of major bleeding after percutaneous biopsy is very low. Hypertension does not appear to significantly increase the risk of major bleeding complications. PMID- 26826088 TI - Hepatic imaging following intra-arterial embolotherapy. AB - PURPOSE: To discuss guidelines and salient imaging findings of solid tumors treated with common intra-arterial procedures used in interventional oncology. METHODS: A meticulous literature search of PubMed-indexed articles was conducted. Key words included "imaging + embolization," "imaging + TACE," "imaging + radioembolization," "imaging + Y90," "mRECIST," and "EASL." Representative post treatment cross-sectional images were obtained from past cases in this institution. RESULTS: Intra-arterial therapy (IAT) in interventional oncology includes bland embolization, chemoembolization, and radioembolization. Solid tumors of the liver are the primary focus of these procedures. Cross-sectional CT and/or MR are the main modalities used to image tumors after treatment. Traditional size-based response criteria (WHO and RECIST) alone are of limited utility in determining response to IAT; tumoral necrosis and enhancement must be considered. Specifically for HCC, the EASL and mRECIST guidelines are becoming widely adopted response criteria to assess these factors. DWI, FDG-PET, and CEUS are modalities that play an adjunctive but controversial role. CONCLUSIONS: Radiologists must be aware that the different forms of intra-arterial therapy yield characteristic findings on cross-sectional imaging. Knowledge of these findings is integral to accurate assessment of tumor response and progression. PMID- 26826089 TI - Comparison of FLT-PET/CT and CECT in gastric cancer diagnosis. AB - AIM: To date, no data are available on the use of 18-fluorothymidine positron emission tomography/computed tomography (FLT-PET/CT) for preoperative gastric cancer staging. Herein, we attempt to assess the value of FLT-PET/CT for preoperative gastric cancer staging in comparison with contrast-enhanced computed tomography (CECT). MATERIALS AND METHODS: In a group of 96 gastric cancer patients, 96 FLT-PET/CT, 56 abdominal cavity CECT, and 51 resective operations were done. All three (FLT-PET/CT, CECT, and resective operation) were done in 29 patients. The results of FLT-PET/CT, CECT, and histopathological examinations were used to assess the ability of FLT-PET/CT and CECT to identify primary tumors, regional nodal metastases, and distant abdominal metastases. Assessment of regional lymph nodes was based on SUVmax in FLT-PET/CT and SAD (short-axis diameter) in CECT. RESULTS: In the group of 56 patients examined with FLT-PET/CT and CECT, identification of the primary tumor was possible in 56 cases (100%) and in 53 cases (94.6%), respectively, (p = 0.013). Using ROC curve, the sensitivity and specificity of FLT-PET/CT in metastatic regional lymph node assessment were higher than those of CECT (p = 0.0033). FLT-PE/CT enabled identification of a greater number of extraregional abdominal metastases than CECT (n = 56; 19 vs. 15, respectively), but the difference was not statistically significant (p > 0.41). CONCLUSIONS: The ability of FLT-PET/CT to identify primary tumors is greater than that of CECT, and thus FLT-PET/CT was better in evaluating regional nodal metastases. FLT-PET/CT enabled identification of a greater number of abdominal metastases than CECT, but the difference was not statistically significant. PMID- 26826090 TI - Image-guided percutaneous drainage: a review. AB - Percutaneous abscess drainage (PAD) has been proven to be a safe, effective, and widely used technique for treatment of patients with intra-abdominal fluid collections. Indications for PAD are ever expanding, and most abscesses are amenable to PAD. PAD is routinely used for treatment of simple unilocular abscesses however more complex collections require a collaborative strategy with surgical services for patient management. PAD is also used as a temporizing procedure for patients who will ultimately require operative intervention. A variety of imaging modalities are used for PAD including ultrasound and CT. Several catheter insertion techniques have proven effective. Complications from PAD are relatively uncommon. PMID- 26826091 TI - Recurrent painful ophthalmoplegia in a patient with diabetes mellitus: Is ophthalmoplegia associated with diabetes mellitus? PMID- 26826092 TI - Dynamics of a haemodynamic headache: A case report and literature review of headache secondary to flow inversion of the internal jugular vein. AB - BACKGROUND: Haemodialysis arteriovenous fistulas have common local and regional complications, but are rarely associated with neurological symptoms. CASE REPORT: A 43-year-old woman presented with short acute episodes of unilateral, non throbbing, severe headache, vertigo and left lateropulsion. She had undergone renal transplantation and had a still-functioning left brachial arteriovenous fistula. No abnormality was detected on neurological examination or on brain parenchymal imaging. Colour Doppler ultrasonography showed a subclavian steal syndrome of the left vertebral artery and reversed flow in the left internal jugular vein. Ligation of the arteriovenous fistula had to be delayed as a result of renal graft dysfunction. Six months later she developed a headache attributed to intracranial hypertension. All symptoms subsided after ligation of the arteriovenous fistula. LITERATURE REVIEW: We identified 16 case reports of central neurological complications attributed to haemodialysis brachial fistulas. Headache descriptions were scarce and were not fully detailed. CONCLUSIONS: The case of our patient suggests that unilateral, episodic, non-throbbing, non postural headache with transient neurological symptoms can be caused by combined arterial and venous flow abnormalities secondary to a high-flow arteriovenous brachial fistula. In this setting, this pattern of headache may precede overt signs of intracranial hypertension and may be used as a warning sign of cerebral venous congestion. PMID- 26826093 TI - Japanese sporadic case of erythrokeratodermia variabilis caused by the connexin 30.3 (GJB4) mutation: Is Glycine 12 a mutational hotspot in the connexin family? PMID- 26826094 TI - The allelopathic effects of invasive plant Solidago canadensis on seed germination and growth of Lactuca sativa enhanced by different types of acid deposition. AB - Invasive species can exhibit allelopathic effects on native species. Meanwhile, the types of acid deposition are gradually changing. Thus, the allelopathic effects of invasive species on seed germination and growth of native species may be altered or even enhanced under conditions with diversified acid deposition. This study aims to assess the allelopathic effects (using leaves extracts) of invasive plant Solidago canadensis on seed germination and growth of native species Lactuca sativa treated with five types of acid deposition with different SO4(2-) to NO3(-) ratios (1:0, sulfuric acid; 5:1, sulfuric-rich acid; 1:1, mixed acid; 1:5, nitric-rich acid; 0:1, nitric acid). Solidago canadensis leaf extracts exhibited significantly allelopathic effects on germination index, vigor index, and germination rate index of L. sativa. High concentration of S. canadensis leaf extracts also similarly exhibited significantly allelopathic effects on root length of L. sativa. This may be due to that S. canadensis could release allelochemicals and then trigger allelopathic effects on seed germination and growth of L. sativa. Acid deposition exhibited significantly negative effects on seedling biomass, root length, seedling height, germination index, vigor index, and germination rate index of L. sativa. This may be ascribed to the decreased soil pH values mediated by acid deposition which could produce toxic effects on seedling growth. Sulfuric acid deposition triggered more toxic effects on seedling biomass and vigor index of L. sativa than nitric acid deposition. This may be attributing to the difference in exchange capacity with hydroxyl groups (OH(-)) between SO4(2-) and NO3(-) as well as the fertilizing effects mediated by nitric deposition. All types of acid deposition significantly enhanced the allelopathic effects of S. canadensis on root length, germination index, vigor index, and germination rate index of L. sativa. This may be due to the negatively synergistic effects of acid deposition and S. canadensis on seed germination and growth of L. sativa. The ratio of SO4(2-) to NO3(-) in acid deposition was an important factor that profoundly affected the allelopathic effects of S. canadensis on the seed germination and growth of L. sativa possibly because the difference in exchange capacity with hydroxyl groups (OH(-)) between SO4(2-) and NO3(-) as well as the fertilizing effects triggered by nitric deposition. Thus, the allelopathic effects of invasive species on seed germination and growth of native plants might be enhanced under increased and diversified acid deposition. PMID- 26826095 TI - From tails to toes: developing nonlethal tissue indicators of mercury exposure in five amphibian species. AB - Exposure to environmental contaminants has been implicated as a factor in global amphibian decline. Mercury (Hg) is a particularly widespread contaminant that biomagnifies in amphibians and can cause a suite of deleterious effects. However, monitoring contaminant exposure in amphibian tissues may conflict with conservation goals if lethal take is required. Thus, there is a need to develop non-lethal tissue sampling techniques to quantify contaminant exposure in amphibians. Some minimally invasive sampling techniques, such as toe-clipping, are common in population-genetic research, but it is unclear if these methods can adequately characterize contaminant exposure. We examined the relationships between mercury (Hg) concentrations in non-lethally sampled tissues and paired whole-bodies in five amphibian species. Specifically, we examined the utility of three different tail-clip sections from four salamander species and toe-clips from one anuran species. Both tail and toe-clips accurately predicted whole-body THg concentrations, but the relationships differed among species and the specific tail-clip section or toe that was used. Tail-clips comprised of the distal 0-2 cm segment performed the best across all salamander species, explaining between 82 and 92% of the variation in paired whole-body THg concentrations. Toe-clips were less effective predictors of frog THg concentrations, but THg concentrations in outer rear toes accounted for up to 79% of the variability in frog whole-body THg concentrations. These findings suggest non-lethal sampling of tails and toes has potential applications for monitoring contaminant exposure and risk in amphibians, but care must be taken to ensure consistent collection and interpretation of samples. PMID- 26826096 TI - Depression in teenagers can be identified with three questions, study shows. PMID- 26826097 TI - Quantitative sensory testing (QST). English version. AB - Quantitative sensory testing (QST) is a standardized and formalized clinical sensitivity test. Testing describes a subjective (psychophysical) method that entails a cooperation of the person to be examined. Within its framework, calibrated stimuli are applied to capture perception and pain thresholds, thus providing information on the presence of sensory plus or minus signs. The presented QST battery imitates natural thermal or mechanical stimuli. The aim is to acquire symptom patterns of sensory loss (for the functioning of the thick and thin nerve fibers) as well as a gain of function (hyperalgesia, allodynia, hyperpathia) with a simultaneous detection of cutaneous and deep tissue sensibility. Most of the tested QST parameters are normally distributed only after a logarithmic transformation (secondary normal distribution)-except the number of paradoxical heat sensations, of cold and heat pain thresholds, and vibration detection thresholds. A complete QST profile can be measured within 1 h. QST is suitable not only for clinical trials but also in practice as a diagnostic method to characterize the function of the somatosensory system-from the peripheral nerve fiber receptor to the projection pathways to the brain. PMID- 26826098 TI - Evaluation of Faecal Salmonella Shedding Among Dogs at Seven Animal Shelters across Texas. AB - Estimates of prevalence of faecal Salmonella shedding among dogs in the United States have varied widely. Surveillance among shelter dogs has been limited, although dogs in animal shelters may be at elevated risk of Salmonella infection because of their previous exposure history as well as factors inherent to shelter environments. Our objectives were to estimate the prevalence of Salmonella shedding among shelter dogs across Texas, to identify risk factors for shedding and to characterize the isolates. Using a repeated cross-sectional study design, we collected faecal samples from dogs on two or three visits to each of seven Texas animal shelters between May 2013 and December 2014. Standard bacteriologic culture methods were used to isolate Salmonella from samples, and isolates were characterized via serotyping and anti-microbial susceptibility testing. The prevalence of faecal Salmonella shedding among sampled dogs was 4.9% (27/554), and within-shelter prevalence ranged from 1.9% to 8.3%. There was a marginal association (P = 0.09) between watery faecal samples and positive Salmonella status, as estimated by a logistic regression model that controlled for shelter as a random effect. However, over 60% of Salmonella-positive dogs had grossly normal faeces. Salmonella prevalence did not vary significantly by age group or sex. The most common serovars were Newport (22%) and Javiana (15%), both of which were widespread among shelters. Resistance to anti-microbial agents was uncommon. The prevalence of faecal Salmonella shedding among shelter dogs in Texas appears to be comparable to that seen among pet dogs in general. PMID- 26826099 TI - Haemodynamic changes in pregnancy: what can we learn from combined datasets? PMID- 26826100 TI - Optimal non-invasive imaging test selection for the diagnosis of ischaemic heart disease. AB - The prevalence of angina is high in the general population, and increases with age in both sexes. Little consensus exists about which test is preferable when one is required for diagnosis, including significant differences in the current US and European guidelines. However, the recent PROMISE and SCOT-HEART trials incorporating the use of CCTA have demonstrated that an anatomical strategy is a reasonable alternative initial approach to use in intermediate-risk patients with stable chest for the diagnosis of IHD. Contemporary approaches should therefore consider both functional and anatomical strategies in an integrated decision making model. PMID- 26826101 TI - Hippocampus and Prefrontal Cortex Predict Distinct Timescales of Activation in the Human Ventral Tegmental Area. AB - The mesolimbic dopamine system contributes to a remarkable variety of behaviors at multiple timescales. Midbrain neurons have fast and slow signaling components, and specific afferent systems, such as the hippocampus (HPC) and prefrontal cortex (PFC), have been demonstrated to drive these components in anesthetized animals. Whether these interactions exist during behavior, however, is unknown. To address this question, we developed a novel analysis of human functional magnetic resonance imaging data that fits models of network excitation and inhibition on ventral tegmental area (VTA) activation. We show that specific afferent systems predict distinct temporal components of midbrain VTA signal. We found that PFC, but not HPC, positively predicted transient, event-evoked VTA activation. In contrast, HPC, but not PFC, positively predicted slow shifts in VTA baseline variability. Thus, unique functional contributions of afferent systems to VTA physiology are detectable at the network level in behaving humans. The findings support models of dopamine function in which dissociable neural circuits support different aspects of motivated behavior via active regulation of tonic and phasic signals. PMID- 26826103 TI - Potential effect of atmospheric warming on grapevine phenology and post-harvest heat accumulation across a range of climates. AB - Carbohydrates are accumulated within the perennial structure of grapevines when their production exceeds the requirements of reproduction and growth. The period between harvest and leaf-fall (the post-harvest period) is a key period for carbohydrate accumulation in relatively warmer grape-growing regions. The level of carbohydrate reserves available for utilisation in the following season has an important effect on canopy growth and yield potential and is therefore an important consideration in vineyard management. In a warming climate, the post harvest period is lengthening and becoming warmer, evidenced through studies in wine regions worldwide that have correlated recent air temperature increases with changing grapevine phenology. Budbreak, flowering, veraison, and harvest have all been observed to be occurring earlier than in previous decades. Additionally, the final stage of the grapevine phenological cycle, leaf-fall, occurs later. This study explored the potential for increased post-harvest carbohydrate accumulation by modelling heat accumulation following harvest dates for the recent climate (1975-2004) and two warmer climate projections with mean temperature anomalies of +1.26 and +2.61 degrees C. Summaries of post-harvest heat accumulation between harvest and leaf-fall were produced for each of Australia's Geographical Indications (wine regions) to provide comparisons from the base temperatures to projected warmer conditions across a range of climates. The results indicate that for warmer conditions, all regions observe earlier occurring budbreak and harvest as well as increasing post-harvest growing degree days accumulation before leaf fall. The level of increase varies depending upon starting climatic condition, with cooler regions experiencing the greatest change. PMID- 26826102 TI - Cc2d1a Loss of Function Disrupts Functional and Morphological Development in Forebrain Neurons Leading to Cognitive and Social Deficits. AB - Loss-of-function (LOF) mutations in CC2D1A cause a spectrum of neurodevelopmental disorders, including intellectual disability, autism spectrum disorder, and seizures, identifying a critical role for this gene in cognitive and social development. CC2D1A regulates intracellular signaling processes that are critical for neuronal function, but previous attempts to model the human LOF phenotypes have been prevented by perinatal lethality in Cc2d1a-deficient mice. To overcome this challenge, we generated a floxed Cc2d1a allele for conditional removal of Cc2d1a in the brain using Cre recombinase. While removal of Cc2d1a in neuronal progenitors using Cre expressed from the Nestin promoter still causes death at birth, conditional postnatal removal of Cc2d1a in the forebrain via calcium/calmodulin-dependent protein kinase II-alpha (CamKIIa) promoter-driven Cre generates animals that are viable and fertile with grossly normal anatomy. Analysis of neuronal morphology identified abnormal cortical dendrite organization and a reduction in dendritic spine density. These animals display deficits in neuronal plasticity and in spatial learning and memory that are accompanied by reduced sociability, hyperactivity, anxiety, and excessive grooming. Cc2d1a conditional knockout mice therefore recapitulate features of both cognitive and social impairment caused by human CC2D1A mutation, and represent a model that could provide much needed insights into the developmental mechanisms underlying nonsyndromic neurodevelopmental disorders. PMID- 26826104 TI - Assessing Antibacterial Potential of Components of Phyllomedusa distincta Skin and its Associated Dermal Microbiota. AB - The granular glands of anuran skin secrete an array of bioactive molecules that protect a frog against pathogens and predators. The skin also harbors a microbial community. Although there is evidence to suggest that the microbiota complement the innate immune defense systems against pathogen infection, the effect of the frog bioactive molecules on its resident microbiota has not yet been fully investigated. In the present study, the skin microbiota of Phyllomedusa distincta obtained from two different geographical areas was evaluated with molecular and culture-based approaches. The antagonistic effects exhibited by the host's microbiota and by a novel dermaseptin peptide isolated from P. distincta skin were investigated. Four isolated bacterial colonies displayed antimicrobial activity against known frog pathogens. Our results were consistent with the hypothesis that microbiota from P. distincta may interact with pathogenic microorganisms to protect a frog's health. On the other hand, the novel dermaseptin peptide exhibited an antimicrobial effect on pathogens as well as on some of the bacteria obtained from the skin microbiota. The richness of bacteria on P. distincta skin was further investigated by 16S rRNA gene clone libraries, which revealed that the family Enterobacteriaceae was prevalent, but a high variability at the species level was observed among individual frogs. Differences observed on the microbiota of frogs from contrasting habitats indicated an influence of the environment on the structure of the skin microbiota of P. distincta. PMID- 26826105 TI - Bevacizumab changes vascular structure and modulates the expression of angiogenic factors in recurrent malignant gliomas. AB - Bevacizumab (BV), a monoclonal antibody against vascular endothelial growth factor (VEGF), is currently used in the treatment of malignant glioma. To understand mechanisms of resistance to BV, we investigated morphological changes in tumor vessels and expression of angiogenic factors, such as VEGF, Flt-1, basic fibroblast growth factor (bFGF), and platelet-derived growth factor-BB (PDGF-BB), in four autopsied tumors after BV treatment. Three patients had glioblastomas; the fourth had a secondary glioblastoma that developed from a diffuse astrocytoma. BV was administered because of recurrence following the use of the Stupp regimen in these four patients. We compared the initial surgical specimen with that obtained after death following BV treatment. Immunohistochemical staining of the autopsied tumors showed that Flt-1 expression increased while VEGF expression was significantly reduced. Additionally, other angiogenic factors, particularly bFGF, were enhanced. Interestingly, the proliferation of endothelial cells was reduced, but remarkable proliferation of pericytes was observed. These results suggest that following BV treatment, glioblastomas can grow tumor vessels by expressing various angiogenic factors. These mechanisms might be important for rapid regrowth and blood brain barrier repair after BV treatment. Inhibition of multiple angiogenic factors will be required to control tumor vessels in glioblastoma. PMID- 26826106 TI - Generalized Recalcitrant Pruritus as the Presenting Manifestation of Hypereosinophilic Syndrome. AB - BACKGROUND AND OBJECTIVE: Pruritus is a frequent occurrence in dermatology, and investigation is often unrevealing. The authors report the case of a 65-year-old man presenting with generalized recalcitrant pruritus as the presenting manifestation of hypereosinophilic syndrome. METHODS AND RESULTS: A 65-year-old man developed intractable pruritus. Results of polymerase chain reaction clonal rearrangement were positive and led to the diagnosis and treatment. The patient also developed massive pulmonary embolism, which can be caused by chronic eosinophilia. CONCLUSIONS: This case highlights the importance of investigating patients with pruritus and unexplained persistent eosinophilia. Hypereosinophilic syndrome must be included in the differential diagnosis, which in this case presented initially as intractable pruritus. Polymerase chain reaction clonal rearrangement was key in reinforcing the diagnosis. PMID- 26826107 TI - Laboratory Studies of Nonlinear Optical Signals for Caries Detection. AB - Multiphoton confocal microscopy and nonlinear spectroscopy are used to investigate the caries process in dentin. Although dentin is a major calcified tissue of the teeth, its organic phase comprises type I collagen fibers. Caries drive dentin demineralization and collagen denaturation. Multiphoton microscopy is a powerful imaging technique: the biological materials are transparent to infrared frequencies and can be excited to penetration depths inaccessible to 1 photon confocal microscopy. The laser excitation greatly reduces photodamage to the sole focal region, and the signal-to-noise ratio is improved significantly. The method has been used to follow pathologic processes involving collagen fibrosis or collagen destruction based on their 2-photon excited fluorescence (2PEF) emission and second harmonic generation (SHG). Combining multiphoton imaging with nonlinear spectroscopy, we demonstrate that both 2PEF and SHG intensity of human dentin are strongly modified during the tooth caries process, and we show that the ratio between SHG and 2PEF signals is a reliable parameter to follow dental caries. The ratio of the SHG/2PEF signals measured by nonlinear optical spectroscopy provides valuable information on the caries process, specifically on the degradation of the organic matrix of dentin. The goal is to bring these nonlinear optical signals to clinical application for caries diagnosis. PMID- 26826108 TI - Pragmatic RCT on the Efficacy of Proximal Caries Infiltration. AB - Proximal caries infiltration has been shown to be efficacious in hampering caries lesion progression when performed by dentists working in a university setting. The aim of this randomized split-mouth, placebo-controlled clinical trial was to assess the efficacy of resin infiltration of proximal caries lesions being performed by several dentists in private practices, in combination with individualized oral hygiene plus noninvasive measures compared with these alone. In this study, 87 children and young adults (with 238 pairs of proximal caries lesions radiographically extending into the inner half of the enamel [E2] or the outer third of the dentin [D1]) were randomly allocated to either 1 of 2 treatments. Test lesions were infiltrated, and a mock treatment was performed in control lesions by 5 German private practitioners. All patients received instructions for a noncariogenic diet, flossing and fluoridation, and individualized noninvasive interventions. The primary outcome was radiographic lesion progression (pairwise comparison) evaluated independently by 2 evaluators who were blinded to treatment allocation. After approximately 10 mo (mean +/- SD 307 +/- 43 d), 92 of 148 lesion pairs in 24 of 38 treated patients who were at high caries risk could be re-evaluated clinically as well as radiographically using individualized bitewing holders, as at baseline; 186 of 204 lesion pairs in 70 of 77 patients (35 of 38 high-risk patients) could be evaluated after 18 mo (mean 542 +/- 110 d). No unwanted effects were observed. After 10 mo, progression was recorded in 2 of 92 test lesions (2%) and in 22 of 92 control lesions (24%) (P= 0.001, McNemar/Obuchowski test; relative risk reduction, 91; 95% confidence interval, 62%-98%). After 18 mo, lesion progression was recorded in all included patients in 10 of 186 test lesions (5%) and in 58 of 186 control lesions (31%) (P< 0.001; relative risk reduction, 83; 95% confidence interval, 67%-91%). Thus, resin infiltration seems to be more efficacious in reducing lesion progression compared with individualized noninvasive measures alone over a period of 18 mo when performed in a private practice setting by various practitioners (German Clinical Trials Register / Deutsches Register Klinischer Studien DRKS00009963). PMID- 26826109 TI - Psychological Interventions for Poor Oral Health: A Systematic Review. AB - The aim of this systematic review and meta-analysis was to study the effectiveness of psychological interventions in adults and adolescents with poor oral health. The review follows the PRISMA guidelines for systematic reviews. The PICO format (population, intervention, comparison, and outcome) was used to define eligible studies. The populations were adults or adolescents (>=13 y of age and independent of others) with poor oral health (defined as dental caries, periodontal disease, and/or peri-implantitis). The interventions were psychological and/or behavioral models and theories, in comparison with traditional oral health education/information. The primary outcomes were dental caries, periodontitis, gingivitis, and peri-implantitis. Secondary outcomes were dental plaque, oral health-related behavior, health-related quality of life, health beliefs and attitudes, self-perceived oral health, and complications/risks. The systematic literature search identified 846 articles in December 2013 and 378 articles in July 2015. In total, 11 articles on 9 randomized controlled trials were found to meet the inclusion criteria. These reported on adults with periodontal disease, and several used motivational interviewing (MI) as their mode of intervention. The CONSORT guidelines and the GRADE approach were used for study appraisal and rating of evidence. The meta analysis showed no statistically significant differences in gingivitis or plaque presence. In addition, a meta-analysis on MI compared with education/information found no statistically significant differences in gingivitis presence. Only 1 meta-analysis-on psychological interventions versus education/information regarding the plaque index-showed a small but statistically significant difference. There were also statistically significant differences reported in favor of psychological interventions in oral health behavior and self-efficacy in toothbrushing. However, the clinical relevance of these differences is difficult to estimate. The certainty of evidence was low. Future research needs to address several methodological issues and not only study adults with periodontal disease but also adolescents and patients with dental caries and peri-implantitis. PMID- 26826110 TI - Translating an Evidence-Based Injury Prevention Program for Implementation in a Home Visitation Setting. AB - Safe N' Sound (SNS), a computer-based childhood injury prevention program, provides individually tailored information to parents about their child's injury risks with specific behavioral recommendations. We translated SNS for implementation in a home visitation organization in order to increase its capacity to effectively address injury prevention and decrease the burden of injury experienced by high-need families. The aim of this study was to identify behavioral and organizational barriers and facilitators to translating and implementing SNS in a home visitation setting. Nurse home visitors (NHVs) participated in semistructured interviews that examined perceptions of program implementation, intervention characteristics, individual characteristics of NHVs, and recommendations for improving implementation. The utility of the program for promoting injury prevention systematically and its alignment with the organization's mission were facilitators of successful implementation. Barriers included NHVs' concerns about overburdening clients and missed educational opportunities related to injury risks not addressed by the program and delayed delivery of educational reports. Findings illustrate the dynamic interactions of intervention characteristics with organizational and individual factors and suggest that customizing implementation to organizational capacity and specific needs may better support successful program implementation in home visitation settings. PMID- 26826112 TI - Double vision. PMID- 26826111 TI - Exploring the Range of Lifestyle Interventions Used in Dutch Health Care Practice: A Qualitative Description. AB - BACKGROUND: The application of evidence-based lifestyle interventions is suboptimal, but little is known what interventions are actually used. This study aimed to explore the range of lifestyle interventions used in Dutch ambulatory health care settings. METHOD: We conducted interviews (n = 67) in purposefully selected hospitals, general practices, and community care organizations. Interviews focused on identifying activities to help patients stop smoking, reduce alcohol consumption, increase physical activity, eat a healthy diet, and lose weight. We also asked who developed the interventions. All reported activities were registered and analyzed. RESULTS: Four categories of health promotion activities emerged: giving advice, making referrals, offering counseling, and providing lifestyle interventions organized separately from the care process. In total, 102 lifestyle interventions were reported. Forty-five interventions were developed by researchers, of which 30 were developed by the Dutch Expert Center on Tobacco Control. Providers did not know the source of 31 interventions. Eighteen interventions were developed by the providers themselves, and eight were based on evidence-based guidelines. CONCLUSIONS: Health promotion activities seemed to be widely present in Dutch health care, in particular smoking cessation interventions. Although health care providers use many different interventions, replacing nontested for evidence-based interventions is required. PMID- 26826113 TI - Long-term effects of physically active academic lessons on physical fitness and executive functions in primary school children. AB - Integrating physical activity into the curriculum has potential health and cognitive benefits in primary school children. The aim of this study was to investigate the effects of physically active academic lessons on cardiovascular fitness, muscular fitness and executive functions. In the current randomized controlled trial, 499 second and third graders within 12 primary schools (mean age = 8.1 +/- 0.7) were randomized to the intervention (n = 249) or control condition (n = 250). The physically active academic lessons were given for 2 consecutive school years, 22 weeks per year, three times a week, with a duration of 20-30 min per lesson. Multiple tests were administered before, between and after the intervention period, measuring cardiovascular fitness, muscular fitness and executive functions. Multilevel analysis accounted for the nested structure of the children within classes and schools. Results showed a larger improvement in speed-coordination (B = -0.70,P = 0.002) and a lower improvement in static strength (B = -0.92,P < : 0.001) for the intervention group compared with the control group. The current lessons did not result in a significant change in executive functions. PMID- 26826115 TI - EC-70124, a Novel Glycosylated Indolocarbazole Multikinase Inhibitor, Reverts Tumorigenic and Stem Cell Properties in Prostate Cancer by Inhibiting STAT3 and NF-kappaB. AB - Cancer stem cells (CSC) contribute to disease progression and treatment failure in prostate cancer because of their intrinsic resistance to current therapies. The transcription factors NF-kappaB and STAT3 are frequently activated in advanced prostate cancer and sustain expansion of prostate CSCs. EC-70124 is a novel chimeric indolocarbazole compound generated by metabolic engineering of the biosynthetic pathways of glycosylated indolocarbazoles, such as staurosporine and rebeccamycin. In vitro kinome analyses revealed that EC-70124 acted as a multikinase inhibitor with potent activity against IKKbeta and JAK2. In this study, we show that EC-70124 blocked concomitantly NF-kappaB and STAT3 in prostate cancer cells and particularly prostate CSCs, which exhibited overactivation of these transcription factors. Phosphorylation of IkB and STAT3 (Tyr705), the immediate targets of IKKbeta and JAK2, respectively, was rapidly inhibited in vitro by EC-70124 at concentrations that were well below plasma levels in mice. Furthermore, the drug blocked activation of NF-kappaB and STAT3 reporters and suppressed transcription of their target genes. Treatment with EC 70124 impaired proliferation and colony formation in vitro and delayed development of prostate tumor xenografts. Notably, EC-70124 had profound effects on the prostate CSC subpopulation both in vitro and in vivo Thus, EC-70124 is a potent inhibitor of the NF-kappaB and STAT3 signaling pathways and blocked tumor growth and maintenance of prostate CSCs. EC-70124 may provide the basis for developing new therapeutic strategies that combine agents directed to the CSC component and the bulk tumor cell population for treatment of advanced prostate cancer. Mol Cancer Ther; 15(5); 806-18. (c)2016 AACR. PMID- 26826114 TI - Perceptual and Brain Response to Odors Is Associated with Body Mass Index and Postprandial Total Ghrelin Reactivity to a Meal. AB - Animal studies have shown that olfactory sensitivity is greater when fasted than when fed. However, human research has generated inconsistent results. One possible explanation for these conflicting findings is metabolic health. Many metabolic peptides, including ghrelin, are moderated by adiposity and influence olfaction and olfactory-guided behaviors. We tested whether the effect of a meal on the perceived intensity of suprathreshold chemosensory stimuli is influenced by body mass index and/or metabolic response to a meal. We found that overweight or obese (n = 13), but not healthy weight (n = 20) subjects perceived odors, but not flavored solutions, as more intense when hungry than when sated. This effect was correlated with reduced postprandial total ghrelin suppression (n = 23) and differential brain response to odors in the cerebellum, as measured with functional magnetic resonance imaging. In contrast, it was unrelated to circulating leptin, glucose, insulin, triglycerides, or free fatty acids; or to odor pleasantness or sniffing (n = 24). These findings demonstrate that the effect of a meal on suprathreshold odor intensity perception is associated with metabolic measures such as body weight and total ghrelin reactivity, supporting endocrine influences on olfactory perception. PMID- 26826116 TI - Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression. AB - Chemotherapy-induced myelosuppression continues to represent the major dose limiting toxicity of cytotoxic chemotherapy, which can be manifested as neutropenia, lymphopenia, anemia, and thrombocytopenia. As such, myelosuppression is the source of many of the adverse side effects of cancer treatment including infection, sepsis, bleeding, and fatigue, thus resulting in the need for hospitalizations, hematopoietic growth factor support, and transfusions (red blood cells and/or platelets). Moreover, clinical concerns raised by myelosuppression commonly lead to chemotherapy dose reductions, therefore limiting therapeutic dose intensity, and reducing the antitumor effectiveness of the treatment. Currently, the only course of treatment for myelosuppression is growth factor support which is suboptimal. These treatments are lineage specific, do not protect the bone marrow from the chemotherapy-inducing cytotoxic effects, and the safety and toxicity of each agent is extremely specific. Here, we describe the preclinical development of G1T28, a novel potent and selective CDK4/6 inhibitor that transiently and reversibly regulates the proliferation of murine and canine bone marrow hematopoietic stem and progenitor cells and provides multilineage protection from the hematologic toxicity of chemotherapy. Furthermore, G1T28 does not decrease the efficacy of cytotoxic chemotherapy on RB1-deficient tumors. G1T28 is currently in clinical development for the reduction of chemotherapy-induced myelosuppression in first- and second-line treatment of small-cell lung cancer. Mol Cancer Ther; 15(5); 783-93. (c)2016 AACR. PMID- 26826117 TI - A Novel Recombinant Anti-CD22 Immunokinase Delivers Proapoptotic Activity of Death-Associated Protein Kinase (DAPK) and Mediates Cytotoxicity in Neoplastic B Cells. AB - The serine/threonine death-associated protein kinases (DAPK) provide pro-death signals in response to (oncogenic) cellular stresses. Lost DAPK expression due to (epi)genetic silencing is found in a broad spectrum of cancers. Within B-cell lymphomas, deficiency of the prototypic family member DAPK1 represents a predisposing or early tumorigenic lesion and high-frequency promoter methylation marks more aggressive diseases. On the basis of protein studies and meta-analyzed gene expression profiling data, we show here that within the low-level context of B-lymphocytic DAPK, particularly CLL cells have lost DAPK1 expression. To target this potential vulnerability, we conceptualized B-cell-specific cytotoxic reconstitution of the DAPK1 tumor suppressor in the format of an immunokinase. After rounds of selections for its most potent cytolytic moiety and optimal ligand part, a DK1KD-SGIII fusion protein containing a constitutive DAPK1 mutant, DK1KD, linked to the scFv SGIII against the B-cell-exclusive endocytic glyco receptor CD22 was created. Its high purity and large-scale recombinant production provided a stable, selectively binding, and efficiently internalizing construct with preserved robust catalytic activity. DK1KD-SGIII specifically and efficiently killed CD22-positive cells of lymphoma lines and primary CLL samples, sparing healthy donor- or CLL patient-derived non-B cells. The mode of cell death was predominantly PARP-mediated and caspase-dependent conventional apoptosis as well as triggering of an autophagic program. The notoriously high apoptotic threshold of CLL could be overcome by DK1KD-SGIII in vitro also in cases with poor prognostic features, such as therapy resistance. The manufacturing feasibility of the novel CD22-targeting DAPK immunokinase and its selective antileukemic efficiency encourage intensified studies towards specific clinical application. Mol Cancer Ther; 15(5); 971-84. (c)2016 AACR. PMID- 26826118 TI - Sequential Combination Therapy of CDK Inhibition and Doxorubicin Is Synthetically Lethal in p53-Mutant Triple-Negative Breast Cancer. AB - Triple-negative breast cancer (TNBC) is an aggressive malignancy in which the tumors lack expression of estrogen receptor, progesterone receptor, and HER2. Hence, TNBC patients cannot benefit from clinically available targeted therapies and rely on chemotherapy and surgery for treatment. While initially responding to chemotherapy, TNBC patients are at increased risk of developing distant metastasis and have decreased overall survival compared with non-TNBC patients. A majority of TNBC tumors carry p53 mutations, enabling them to bypass the G1 checkpoint and complete the cell cycle even in the presence of DNA damage. Therefore, we hypothesized that TNBC cells are sensitive to cell-cycle-targeted combination therapy, which leaves nontransformed cells unharmed. Our findings demonstrate that sequential administration of the pan-CDK inhibitor roscovitine before doxorubicin treatment is synthetically lethal explicitly in TNBC cells. Roscovitine treatment arrests TNBC cells in the G2-M cell-cycle phase, priming them for DNA damage. Combination treatment increased frequency of DNA double strand breaks, while simultaneously reducing recruitment of homologous recombination proteins compared with doxorubicin treatment alone. Furthermore, this combination therapy significantly reduced tumor volume and increased overall survival compared with single drug or concomitant treatment in xenograft studies. Examination of isogenic immortalized human mammary epithelial cells and isogenic tumor cell lines found that abolishment of the p53 pathway is required for combination-induced cytotoxicity, making p53 a putative predictor of response to therapy. By exploiting the specific biologic and molecular characteristics of TNBC tumors, this innovative therapy can greatly impact the treatment and care of TNBC patients. Mol Cancer Ther; 15(4); 593-607. (c)2016 AACR. PMID- 26826119 TI - Gastric Adenocarcinomas Express the Glycosphingolipid Gb3/CD77: Targeting of Gastric Cancer Cells with Shiga Toxin B-Subunit. AB - The B-subunit of the bacterial Shiga toxin (STxB), which is nontoxic and has low immunogenicity, can be used for tumor targeting of breast, colon, and pancreatic cancer. Here, we tested whether human gastric cancers, which are among the most aggressive tumor entities, express the cellular receptor of Shiga toxin, the glycosphingolipid globotriaosylceramide (Gb3/CD77). The majority of cases showed an extensive staining for Gb3 (36/50 cases, 72%), as evidenced on tissue sections of surgically resected specimen. Gb3 expression was detected independent of type (diffuse/intestinal), and was negatively correlated to increasing tumor-node metastasis stages (P = 0.0385), as well as with markers for senescence. Gb3 expression in nondiseased gastric mucosa was restricted to chief and parietal cells at the bottom of the gastric glands, and was not elevated in endoscopic samples of gastritis (n = 10). Gb3 expression in established cell lines of gastric carcinoma was heterogeneous, with 6 of 10 lines being positive, evidenced by flow cytometry. STxB was taken up rapidly by live Gb3-positive gastric cancer cells, following the intracellular retrograde transport route, avoiding lysosomes and rapidly reaching the Golgi apparatus and the endoplasmic reticulum. Treatment of the Gb3-expressing gastric carcinoma cell line St3051 with STxB coupled to SN38, the active metabolite of the topoisomerase type I inhibitor irinotecan, resulted in >100-fold increased cytotoxicity, as compared with irinotecan alone. No cytotoxicity was observed on gastric cancer cell lines lacking Gb3 expression, demonstrating receptor specificity of the STxB-SN38 compound. Thus, STxB is a highly specific transport vehicle for cytotoxic agents in gastric carcinoma. Mol Cancer Ther; 15(5); 1008-17. (c)2016 AACR. PMID- 26826120 TI - Demographic factors associated with moral sensitivity among nursing students. AB - BACKGROUND: Today's healthcare environment is often characterized by an ethically demanding work situation, and nursing students need to prepare to meet ethical challenges in their future role. Moral sensitivity is an important aspect of the ethical decision-making process, but little is known regarding nursing students' moral sensitivity and its possible development during nursing education. OBJECTIVES: The aims of this study were to investigate moral sensitivity among nursing students, differences in moral sensitivity according to sample sub-group, and the relation between demographic characteristics of nursing students and moral sensitivity. RESEARCH DESIGN: A convenience sample of 299 nursing students from one university completed a questionnaire comprising questions about demographic information and the revised Moral Sensitivity Questionnaire. With the use of SPSS, non-parametric statistics, including logistic regression models, were used to investigate the relationship between demographic characteristics and moral sensitivity. Ethical considerations: The study followed the regulations according to the Swedish Ethical Review Act and was reviewed by the Ethics Committee of South-East Sweden. FINDINGS: The findings showed that mean scores of nursing students' moral sensitivity were found in the middle to upper segment of the rating scale. Multivariate analysis showed that gender (odds ratio = 3.32), age (odds ratio = 2.09; 1.73), and parental status (odds ratio = 0.31) were of relevance to nursing students' moral sensitivity. Academic year was found to be unrelated to moral sensitivity. DISCUSSION AND CONCLUSION: These demographic aspects should be considered when designing ethics education for nursing students. Future studies should continue to investigate moral sensitivity in nursing students, such as if and how various pedagogical strategies in ethics may contribute to moral sensitivity in nursing students. PMID- 26826121 TI - Human rights conflicts experienced by nurses migrating between developed countries. AB - BACKGROUND: Some developed countries have recently changed their role in the context of international recruitment, becoming donors due to socio-economical and political factors such as recessions. This is also the case in Italy, where there has been a flow of immigrant nurses out of the country that has been documented over the past several years. In a short time, it has become a donor country to other developed European countries, such as the United Kingdom. AIMS: To advance knowledge in the context of human rights conflicts and ethical implications of the decision-making process of nurses who migrate between developed countries, such as from Italy to the United Kingdom, during times of recession. RESEARCH DESIGN: A case study based on the descriptive phenomenological approach was undertaken in 2014. Participants and research context: A total of 26 Italian newly graduated nurses finding a job in the United Kingdom were interviewed via Skype and telephone. Ethical considerations: The Internal Review Board of the University approved the project. FINDINGS: In accordance with the descriptive phenomenological approach undertaken, three main themes emerged: (1) escaping from the feeling of being refused/rejected in order to be desired, (2) perceiving themselves respected, as a person and as a nurse, in a growth project and (3) returning if the country changes its strategy regarding nurses. DISCUSSION: Ethical implications in the context of human rights, such as autonomy of the decision, social justice and reciprocal obligation, non-maleficence and double effect, have been discussed. CONCLUSION: The call for investing in nurses and nurses' care in developed countries facing recession is urgent. Investing in nurses means respecting individuals and citizens who are at risk of developing health problems during the recession. PMID- 26826122 TI - Uniforms in dementia care: A barrier or a necessity? AB - This is a case study of an ethical dilemma concerning the appropriateness of encouraging care-staff, working within a dementia care home, to either wear a clinical uniform or not to wear a clinical uniform in practice. It is proposed that people living with dementia may sustain higher levels of wellbeing if care staff wear clothes that are more akin to their care home environment, for example, wearing similar clothes to the residents or even wearing pyjamas and nightwear during a night shift. The counter argument is that the practice may lead to greater levels of distress due to disorientation, increased potential for infection and inability to identify nurses when needed. PMID- 26826123 TI - An Antibody Biosensor Establishes the Activation of the M1 Muscarinic Acetylcholine Receptor during Learning and Memory. AB - Establishing the in vivo activation status of G protein-coupled receptors would not only indicate physiological roles of G protein-coupled receptors but would also aid drug discovery by establishing drug/receptor engagement. Here, we develop a phospho-specific antibody-based biosensor to detect activation of the M1 muscarinic acetylcholine receptor (M1 mAChR) in vitro and in vivo Mass spectrometry phosphoproteomics identified 14 sites of phosphorylation on the M1 mAChR. Phospho-specific antibodies to four of these sites established that serine at position 228 (Ser(228)) on the M1 mAChR showed extremely low levels of basal phosphorylation that were significantly up-regulated by orthosteric agonist stimulation. In addition, the M1 mAChR-positive allosteric modulator, 1-(4 methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, enhanced acetylcholine-mediated phosphorylation at Ser(228) These data supported the hypothesis that phosphorylation at Ser(228) was an indicator of M1 mAChR activation. This was further supported in vivo by the identification of phosphorylated Ser(228) on the M1 mAChR in the hippocampus of mice following administration of the muscarinic ligands xanomeline and 1-(4-methoxybenzyl)-4-oxo 1,4-dihydroquinoline-3-carboxylic acid. Finally, Ser(228) phosphorylation was seen to increase in the CA1 region of the hippocampus following memory acquisition, a response that correlated closely with up-regulation of CA1 neuronal activity. Thus, determining the phosphorylation status of the M1 mAChR at Ser(228) not only provides a means of establishing receptor activation following drug treatment both in vitro and in vivo but also allows for the mapping of the activation status of the M1 mAChR in the hippocampus following memory acquisition thereby establishing a link between M1 mAChR activation and hippocampus-based memory and learning. PMID- 26826124 TI - T Cell Receptor-induced Nuclear Factor kappaB (NF-kappaB) Signaling and Transcriptional Activation Are Regulated by STIM1- and Orai1-mediated Calcium Entry. AB - T cell activation following antigen binding to the T cell receptor (TCR) involves the mobilization of intracellular Ca(2+) to activate the key transcription factors nuclear factor of activated T lymphocytes (NFAT) and NF-kappaB. The mechanism of NFAT activation by Ca(2+) has been determined. However, the role of Ca(2+) in controlling NF-kappaB signaling is poorly understood, and the source of Ca(2+) required for NF-kappaB activation is unknown. We demonstrate that TCR- but not TNF-induced NF-kappaB signaling upstream of IkappaB kinase activation absolutely requires the influx of extracellular Ca(2+) via STIM1-dependent Ca(2+) release-activated Ca(2+)/Orai channels. We further show that Ca(2+) influx controls phosphorylation of the NF-kappaB protein p65 on Ser-536 and that this posttranslational modification controls its nuclear localization and transcriptional activation. Notably, our data reveal that this role for Ca(2+) is entirely separate from its upstream control of IkappaBalpha degradation, thereby identifying a novel Ca(2+)-dependent distal step in TCR-induced NF-kappaB activation. Finally, we demonstrate that this control of distal signaling occurs via Ca(2+)-dependent PKCalpha-mediated phosphorylation of p65. Thus, we establish the source of Ca(2+) required for TCR-induced NF-kappaB activation and define a new distal Ca(2+)-dependent checkpoint in TCR-induced NF-kappaB signaling that has broad implications for the control of immune cell development and T cell functional specificity. PMID- 26826125 TI - A Hippo and Fibroblast Growth Factor Receptor Autocrine Pathway in Cholangiocarcinoma. AB - Herein, we have identified cross-talk between the Hippo and fibroblast growth factor receptor (FGFR) oncogenic signaling pathways in cholangiocarcinoma (CCA). Yes-associated protein (YAP) nuclear localization and up-regulation of canonical target genes was observed in CCA cell lines and a patient-derived xenograft (PDX). Expression of FGFR1, -2, and -4 was identified in human CCA cell lines, driven, in part, by YAP coactivation of TBX5. In turn, FGFR signaling in a cell line with minimal basal YAP expression induced its cellular protein expression and nuclear localization. Treatment of YAP-positive CCA cell lines with BGJ398, a pan-FGFR inhibitor, resulted in a decrease in YAP activation. FGFR activation of YAP appears to be driven largely by FGF5 activation of FGFR2, as siRNA silencing of this ligand or receptor, respectively, inhibited YAP nuclear localization. BGJ398 treatment of YAP-expressing cells induced cell death due to Mcl-1 depletion. In a YAP-associated mouse model of CCA, expression of FGFR 1, 2, and 4 was also significantly increased. Accordingly, BGJ398 treatment was tumor suppressive in this model and in a YAP-positive PDX model. These preclinical data suggest not only that the YAP and Hippo signaling pathways culminate in an Mcl-1 regulated tumor survival pathway but also that nuclear YAP expression may be a biomarker to employ in FGFR-directed therapy. PMID- 26826126 TI - Ablation of the Sox11 Gene Results in Clefting of the Secondary Palate Resembling the Pierre Robin Sequence. AB - Mouse gene inactivation has shown that the transcription factor Sox11 is required for mouse palatogenesis. However, whether Sox11 is primarily involved in the regulation of palatogenesis still remains elusive. In this study, we explored the role ofSox11in palatogenesis by analyzing the developmental mechanism in cleft palate formation in mutants deficient in Sox11. Sox11 is expressed both in the developing palatal shelf and in the surrounding structures, including the mandible. We found that cleft palate occurs only in the mutant in which Sox11is directly deleted. As in the wild type, the palatal shelves in the Sox11 mutant undergo outgrowth in a downward direction and exhibit potential for fusion and elevation. However, mutant palatal shelves encounter clefting, which is associated with a malpositioned tongue that results in physical obstruction of palatal shelf elevation at embryonic day 14.5 (E14.5). We found that loss of Sox11led to reduced cell proliferation in the developing mandibular mesenchyme via Cyclin D1, leading to mandibular hypoplasia, which blocks tongue descent. Extensive analyses of gene expression inSox11 deficiency identified FGF9 as a potential candidate target of Sox11 in the modulation of cell proliferation both in the mandible and the palatal shelf between E12.5 and E13.5. Finally we show, using in vitro assays, that Sox11 directly regulates the expression of Fgf9 and that application of FGF9 protein to Sox11-deficient palatal shelves restores the rate of BrdU incorporation. Taken together, the palate defects presented in the Sox11 loss mutant mimic the clefting in the Pierre Robin sequence in humans. PMID- 26826127 TI - Valosin-containing Protein (VCP)/p97 Segregase Mediates Proteolytic Processing of Cockayne Syndrome Group B (CSB) in Damaged Chromatin. AB - Cockayne syndrome group A and B (CSB) proteins act in transcription-coupled repair, a subpathway of nucleotide excision repair. Here we demonstrate that valosin-containing protein (VCP)/p97 segregase functions in ultraviolet radiation (UVR)-induced ubiquitin-mediated CSB degradation. We show that VCP/p97 inhibition and siRNA-mediated ablation of VCP/p97 and its cofactors UFD1 and UBXD7 impair CSB degradation. VCP/p97 inhibition also results in the accumulation of CSB in chromatin. Moreover, VCP/p97 interacts with both native and ubiquitin-conjugated forms of CSB. The localized cellular UVR exposures lead to VCP/p97 accumulation at DNA damage spots, forming distinct UVR-induced foci. However, manifestation of VCP/p97 foci is independent of CSB and UBXD7. Furthermore, VCP/p97 and UBXD7 associate with the Cockayne syndrome group A-DDB1-Cul4A complex, an E3 ligase responsible for CSB ubiquitination. Compromising proteasome and VCP/p97 function allows accumulation of both native and ubiquitinated CSB and results in an increase of UBXD7, proteasomal RPN2, and Sug1 in the chromatin compartment. Surprisingly, both biochemical inhibition and genetic defect of VCP/p97 enhance the recovery of RNA synthesis following UVR, whereas both VCP/p97 and proteasome inhibitions decrease cell viability. Our findings reveal a new role of VCP/p97 segregase in the timely processing of ubiquitinated CSB from damaged chromatin. PMID- 26826128 TI - Differential Roles of Protein Complexes NOX1-NOXO1 and NOX2-p47phox in Mediating Endothelial Redox Responses to Oscillatory and Unidirectional Laminar Shear Stress. AB - The endothelium is exposed to various flow patterns such as vasoprotective unidirectional laminar shear stress (LSS) and atherogenic oscillatory shear stress (OSS). A software-controlled, valve-operated OsciFlow device with parallel chambers was used to apply LSS and OSS to endothelial cells. Although LSS inhibited superoxide over time, OSS time-dependently increased superoxide production from endothelial cells. Immunocytochemical staining revealed that, at resting state, p47phox colocalizes with NOX2, whereas NOXO1 colocalizes with NOX1. RNAi of p47phox had no effects on superoxide or NO production in response to OSS but significantly reduced NO production in LSS, implicating a p47phox bound NADPH oxidase (NOX) in mediating basal NO production. Indeed, RNAi of p47phox inhibited endothelial nitric oxide synthase (eNOS) serine 1179 phosphorylation, whereas PEG-catalase scavenging of intracellular hydrogen peroxide or RNAi of NOX2 produced similar results, indicating a role of NOX2/p47phox-derived hydrogen peroxide in mediating the basal activity of NO production from eNOS. In contrast, RNAi of NOXO1 resulted in no significant changes in NO and superoxide levels in response to LSS but significantly reduced superoxide while increasing NO in response to OSS. Furthermore, we identified, for the first time, that OSS uncouples eNOS, which was corrected by RNAi of NOXO1. In summary, LSS activates the NOX2-p47phox complex to activate eNOS phosphorylation and NO production. OSS instead activates the NOX1-NOXO1 complex to uncouple eNOS. These results demonstrate differential roles of NOXs in modulating the redox state in response to different shear stresses, which may promote the development of novel therapeutic agents to mimic the protective effects of LSS while inhibiting the injurious effects of OSS. PMID- 26826129 TI - Insights into the mechanisms of RNA secondary structure destabilization by the HIV-1 nucleocapsid protein. AB - The mature HIV-1 nucleocapsid protein NCp7 (NC) plays a key role in reverse transcription facilitating the two obligatory strand transfers. Several properties contribute to its efficient chaperon activity: preferential binding to single-stranded regions, nucleic acid aggregation, helix destabilization, and rapid dissociation from nucleic acids. However, little is known about the relationships between these different properties, which are complicated by the ability of the protein to recognize particular HIV-1 stem-loops, such as SL1, SL2, and SL3, with high affinity and without destabilizing them. These latter properties are important in the context of genome packaging, during which NC is part of the Gag precursor. We used NMR to investigate destabilization of the full length TAR (trans activating response element) RNA by NC, which is involved in the first strand transfer step of reverse transcription. NC was used at a low protein:nucleotide (nt) ratio of 1:59 in these experiments. NMR data for the imino protons of TAR identified most of the base pairs destabilized by NC. These base pairs were adjacent to the loops in the upper part of the TAR hairpin rather than randomly distributed. Gel retardation assays showed that conversion from the initial TAR-cTAR complex to the fully annealed form occurred much more slowly at the 1:59 ratio than at the higher ratios classically used. Nevertheless, NC significantly accelerated the formation of the initial complex at a ratio of 1:59. PMID- 26826130 TI - RNA-seq of human reference RNA samples using a thermostable group II intron reverse transcriptase. AB - Next-generation RNA sequencing (RNA-seq) has revolutionized our ability to analyze transcriptomes. Current RNA-seq methods are highly reproducible, but each has biases resulting from different modes of RNA sample preparation, reverse transcription, and adapter addition, leading to variability between methods. Moreover, the transcriptome cannot be profiled comprehensively because highly structured RNAs, such as tRNAs and snoRNAs, are refractory to conventional RNA seq methods. Recently, we developed a new method for strand-specific RNA-seq using thermostable group II intron reverse transcriptases (TGIRTs). TGIRT enzymes have higher processivity and fidelity than conventional retroviral reverse transcriptases plus a novel template-switching activity that enables RNA-seq adapter addition during cDNA synthesis without using RNA ligase. Here, we obtained TGIRT-seq data sets for well-characterized human RNA reference samples and compared them to previous data sets obtained for these RNAs by the Illumina TruSeq v2 and v3 methods. We find that TGIRT-seq recapitulates the relative abundance of human transcripts and RNA spike-ins in ribo-depleted, fragmented RNA samples comparably to non-strand-specific TruSeq v2 and better than strand specific TruSeq v3. Moreover, TGIRT-seq is more strand specific than TruSeq v3 and eliminates sampling biases from random hexamer priming, which are inherent to TruSeq. The TGIRT-seq data sets also show more uniform 5' to 3' gene coverage and identify more splice junctions, particularly near the 5' ends of mRNAs, than do the TruSeq data sets. Finally, TGIRT-seq enables the simultaneous profiling of mRNAs and lncRNAs in the same RNA-seq experiment as structured small ncRNAs, including tRNAs, which are essentially absent with TruSeq. PMID- 26826131 TI - Methylation of yeast ribosomal protein Rpl3 promotes translational elongation fidelity. AB - Rpl3, a highly conserved ribosomal protein, is methylated at histidine 243 by the Hpm1 methyltransferase in Saccharomyces cerevisiae. Histidine 243 lies close to the peptidyl transferase center in a functionally important region of Rpl3 designated as the basic thumb that coordinates the decoding, peptidyl transfer, and translocation steps of translation elongation. Hpm1 was recently implicated in ribosome biogenesis and translation. However, the biological role of methylation of its Rpl3 substrate has not been identified. Here we interrogate the role of Rpl3 methylation at H243 by investigating the functional impact of mutating this histidine residue to alanine (rpl3-H243A). Akin to Hpm1-deficient cells, rpl3-H243A cells accumulate 35S and 23S pre-rRNA precursors to a similar extent, confirming an important role for histidine methylation in pre-rRNA processing. In contrast, Hpm1-deficient cells but not rpl3-H243A mutants show perturbed levels of ribosomal subunits. We show that Hpm1 has multiple substrates in different subcellular fractions, suggesting that methylation of proteins other than Rpl3 may be important for controlling ribosomal subunit levels. Finally, translational fidelity assays demonstrate that like Hpm1-deficient cells, rpl3 H243A mutants have defects in translation elongation resulting in decreased translational accuracy. These data suggest that Rpl3 methylation at H243 is playing a significant role in translation elongation, likely via the basic thumb, but has little impact on ribosomal subunit levels. Hpm1 is therefore a multifunctional methyltransferase with independent roles in ribosome biogenesis and translation. PMID- 26826132 TI - Two-headed tetraphosphate cap analogs are inhibitors of the Dcp1/2 RNA decapping complex. AB - Dcp1/2 is the major eukaryotic RNA decapping complex, comprised of the enzyme Dcp2 and activator Dcp1, which removes the 5' m(7)G cap from mRNA, committing the transcript to degradation. Dcp1/2 activity is crucial for RNA quality control and turnover, and deregulation of these processes may lead to disease development. The molecular details of Dcp1/2 catalysis remain elusive, in part because both cap substrate (m(7)GpppN) and m(7)GDP product are bound by Dcp1/2 with weak (mM) affinity. In order to find inhibitors to use in elucidating the catalytic mechanism of Dcp2, we screened a small library of synthetic m(7)G nucleotides (cap analogs) bearing modifications in the oligophosphate chain. One of the most potent cap analogs, m(7)GpSpppSm(7)G, inhibited Dcp1/2 20 times more efficiently than m(7)GpppN or m(7)GDP. NMR experiments revealed that the compound interacts with specific surfaces of both regulatory and catalytic domains of Dcp2 with submillimolar affinities. Kinetics analysis revealed that m(7)GpSpppSm(7)G is a mixed inhibitor that competes for the Dcp2 active site with micromolar affinity. m(7)GpSpppSm(7)G-capped RNA undergoes rapid decapping, suggesting that the compound may act as a tightly bound cap mimic. Our identification of the first small molecule inhibitor of Dcp2 should be instrumental in future studies aimed at understanding the structural basis of RNA decapping and may provide insight toward the development of novel therapeutically relevant decapping inhibitors. PMID- 26826133 TI - 'Real-world' management and outcomes of patients with paroxysmal vs. non paroxysmal atrial fibrillation in Europe: the EURObservational Research Programme Atrial Fibrillation (EORP-AF) General Pilot Registry. AB - AIMS: Atrial fibrillation (AF) has different presentations (first detected, paroxysmal, persistent, permanent), with uncertain impact on outcome. The aim of this study was to investigate clinical presentation, management, and outcome of paroxysmal and non-paroxysmal AFs within the EURObservational Research Programme Atrial Fibrillation General Pilot Registry. METHODS AND RESULTS: Overall 2589 patients with available 1-year follow-up data were evaluated according to AF type. Patients with paroxysmal AF (26.8%) were younger, had lower prevalence of heart disease (particularly valvular), and major co-morbidities, as well as lower CHADS2, CHA2DS2-VASc, and HAS-BLED scores. Patients with first-detected AF (29.9%) had characteristics similar to persistent AF patients (25.9%), but lower use of oral anticoagulants. Patients with permanent AF represented 17.4% of the cohort. At 1 year, the rate of stroke/transient ischaemic attack and thromboembolism was low (0.6-1.0%) and did not differ between paroxysmal and non paroxysmal AFs. All-cause mortality was higher in non-paroxysmal vs. paroxysmal AF (log rank test, P = 0.0018). Using a multivariable Cox model, non-paroxysmal AF was not an independent predictor of death during follow-up. Independent predictors of death were age, chronic heart failure, chronic kidney disease, diabetes, restrictive cardiomyopathy, and physical activity. CONCLUSION: In this 'real-world' contemporary observational registry, patients with non-paroxysmal AF had a worse outcome, in terms of all-cause mortality, which was related to a more severe clinical profile. The risk of stroke at 1 year was relatively low, perhaps reflecting the high rates of anticoagulation use in this cohort. PMID- 26826134 TI - Low rate of asymptomatic cerebral embolism and improved procedural efficiency with the novel pulmonary vein ablation catheter GOLD: results of the PRECISION GOLD trial. AB - AIMS: This prospective, multicentre study (PRECISION GOLD) evaluated the incidence of asymptomatic cerebral embolism (ACE) after pulmonary vein isolation (PVI) using a new gold multi-electrode radiofrequency (RF) ablation catheter, pulmonary vein ablation catheter (PVAC) GOLD. Also, procedural efficiency of PVAC GOLD was compared with ERACE. The ERACE study demonstrated that a low incidence of ACE can be achieved with a platinum multi-electrode RF catheter (PVAC) combined with procedural manoeuvres to reduce emboli. METHODS AND RESULTS: A total of 51 patients with paroxysmal atrial fibrillation (AF) (age 57 +/- 9 years, CHA2DS2-VASc score 1.4 +/- 1.4) underwent AF ablation with PVAC GOLD. Continuous oral anticoagulation using vitamin K antagonists, submerged catheter introduction, and heparinization (ACT >= 350 s prior to ablation) were applied. Cerebral magnetic resonance imaging (MRI) scans were performed within 48 h before and 16-72 h post-ablation. Cognitive function assessed by the Mini-Mental State Exam at baseline and 30 days post-ablation. New post-procedural ACE occurred in only 1 of 48 patients (2.1%) and was not detectable on MRI after 30 days. The average number of RF applications per patient to achieve PVI was lower in PRECISION GOLD (20.3 +/- 10.0) than in ERACE (28.8 +/- 16.1; P = 0.001). Further, PVAC GOLD ablations resulted in significantly fewer low-power (<3 W) ablations (15 vs. 23%, 5 vs. 10% and 2 vs. 7% in 4:1, 2:1, and 1:1 bipolar:unipolar energy modes, respectively). Mini-Mental State Exam was unchanged in all patients. CONCLUSION: Atrial fibrillation ablation with PVAC GOLD in combination with established embolic lowering manoeuvres results in a low incidence of ACE. Pulmonary vein ablation catheter GOLD demonstrates improved biophysical efficiency compared with platinum PVAC. TRIAL REGISTRATION: ClinicalTrials.gov NCT01767558. PMID- 26826135 TI - Reduction of inappropriate anti-tachycardia pacing therapies and shocks by a novel suite of detection algorithms in heart failure patients with cardiac resynchronization therapy defibrillators: a historical comparison of a prospective database. AB - AIMS: Implantable cardioverter defibrillators improve survival of patients at risk for ventricular arrhythmias, but inappropriate shocks occur in up to 30% of patients and have been associated with worse quality of life and prognosis. In heart failure patients with cardiac resynchronization therapy defibrillators (CRT Ds), we evaluated whether a new generation of detection and discrimination algorithms reduces inappropriate shocks. METHODS AND RESULTS: We analysed 1983 Medtronic CRT-D patients (80% male, 67 +/- 10 years), 1368 with standard devices (Control CRT-D) and 615 with new generation devices (New CRT-D). Expert electrophysiologists reviewed and classified the electrograms of all device detected ventricular tachycardia/fibrillation episodes. Total follow-up was 3751 patients-years. Incidence of inappropriate shocks at 1 year was 2.8% [95% confidence interval (CI) = 2.0-3.5] in Control CRT-D and 0.9% (CI = 0.4-2.2) in New CRT-D (hazard ratio = 0.37, CI = 0.21-0.66, P < 0.001). In New CRT-D, inappropriate shocks were reduced by 77% [incidence rate ratio (IRR) = 0.23, CI = 0.16-0.35, P < 0.001] and inappropriate anti-tachycardia pacing by 81% (IRR = 0.19, CI = 0.11-0.335, P < 0.001). Annual rate per 100 patient-years for appropriate VF detections was 3.0 (CI = 2.1-4.2) in New CRT-D and 3.2 (CI = 2.1 5.0) in Control CRT-D (P = 0.68), for syncope was 0.4 (CI = 0.2-0.9) in New CRT-D and 0.7 (CI = 0.5-1.0) in Control CRT-D (P = 0.266), and for death was 1.0 (CI = 0.6-1.6) in New CRT-D and 3.5 (CI = 3.0-4.1) in Control CRT-D (P < 0.001). CONCLUSION: Detection and discrimination algorithms used in new generation CRT-D significantly reduced inappropriate shocks when compared with standard CRT-D. This result, with no compromise on VF sensitivity or risk of syncope, has important implications for patients' quality of life and prognosis. PMID- 26826136 TI - Phrenic paralysis during cardiac electronic device implantation: incidence, causes and clinical course. AB - AIMS: Phrenic paralysis is a known complication of central venous catheterization, but it is not listed as a complication related to cardiac implantable electronic device (CIED) implants. The aim of this study is to describe the incidence, causes, clinical picture, and management of phrenic paralysis occurring in this scenario. METHODS AND RESULTS: We retrospectively analysed data from our CIED implantation database and identified those patients who suffered phrenic paralysis during the implantation procedure. Four of 891 patients (subclavian puncture in 626) developed phrenic paralysis during pacemaker or defibrillator implant procedures. Severe respiratory failure needing ventilatory support occurred in two, being the phrenic paralysis transient in all of the cases. CONCLUSIONS: Transient phrenic paralysis may occur during CIED implantation probably related to the infiltration of local anaesthesia in the subclavian area. Mechanism, prevention, and management are discussed. PMID- 26826137 TI - Circulating intermediate CD14++CD16+monocytes are increased in patients with atrial fibrillation and reflect the functional remodelling of the left atrium. AB - AIMS: A recent large clinical study demonstrated the association between intermediate CD14++CD16+monocytes and cardiovascular events. However, whether that monocyte subset contributes to the pathogenesis of atrial fibrillation (AF) has not been clarified. We compared the circulating monocyte subsets in AF patients and healthy people, and investigated the possible role of intermediate CD14++CD16+monocytes in the pathophysiology of AF. METHODS AND RESULTS: This case control study included 44 consecutive AF patients without systemic diseases referred for catheter ablation at our hospital, and 40 healthy controls. Patients with systemic diseases, including structural heart disease, hepatic or renal dysfunction, collagen disease, malignancy, and inflammation were excluded. Monocyte subset analyses were performed (three distinct human monocyte subsets: classical CD14++CD16-, intermediate CD14++CD16+, and non-classical CD14+CD16++monocytes). We compared the monocyte subsets and evaluated the correlation with other clinical findings. A total of 60 participants (30 AF patients and 30 controls as an age-matched group) were included after excluding 14 AF patients due to inflammation. Atrial fibrillation patients had a higher proportion of circulating intermediate CD14++CD16+monocytes than the controls (17.0 +/- 9.6 vs. 7.5 +/- 4.1%, P < 0.001). A multivariable logistic regression analysis demonstrated that only the proportion of intermediate CD14++CD16+monocytes (odds ratio: 1.316; 95% confidence interval: 1.095-1.582, P = 0.003) was independently associated with the presence of AF. Intermediate CD14++CD16+monocytes were negatively correlated with the left atrial appendage flow during sinus rhythm (r= -0.679, P = 0.003) and positively with the brain natriuretic peptide (r = 0.439, P = 0.015). CONCLUSION: Intermediate CD14++CD16+monocytes might be closely related to the pathogenesis of AF and reflect functional remodelling of the left atrium. PMID- 26826138 TI - The multiple proarrhythmic roles of cardiac calcium-handling abnormalities: triggered activity, conduction abnormalities, beat-to-beat variability, and adverse remodelling. PMID- 26826139 TI - Ablation of atrial fibrillation in patients >=75 years: long-term clinical outcome and safety. AB - AIMS: The prevalence of atrial fibrillation (AF) increases with age. Catheter ablation is an established treatment option for patients with symptomatic AF. We sought to determine the safety and long-term clinical efficacy of AF ablation in patients >=75 years. METHODS AND RESULTS: Patients >=75 years with symptomatic, drug-refractory AF were included in the study. Circumferential pulmonary vein isolation (PVI) was performed in all patients, extended to ablation of complex fractionated atrial electrograms, and/or linear lesions in PVI non-responders. Retrospective follow-up (FU) was based on routine outpatient clinic visits and regular telephone interviews. A total of 94 patients (54 male, age 78 +/- 2 years, and left atrium diameter 46 +/- 6 mm) with drug-refractory AF [55/94 (59%) paroxysmal AF (PAF), 29/94 (31%) persistent AF, and 10/94 (11%) long-standing persistent AF] underwent ablation. Follow-up was obtained in 93/94 (99%) patients. Following a single procedure, 35/93 (38%) patients were in stable sinus rhythm (SR; 46% PAF, 31% persistent AF, and 10% long-standing persistent AF) after a mean FU of 37 +/- 20 months. After a mean of 1.5 +/- 0.6 procedures, 55/93 (59%) patients were ultimately in stable SR (76% PAF, 41% persistent AF, and 20% long-standing persistent AF). In a total of 137 procedures, 8 major (5.8%) and 26 minor (19%) complications occurred. CONCLUSIONS: Catheter ablation in patients >=75 years is associated with a favourable clinical long-term outcome in patients with PAF, while results are less promising in persistent or long standing persistent patients. The safety profile of AF ablation in patients >=75 years is comparable with patients of younger age. PMID- 26826140 TI - Health Care Professionals' Knowledge Regarding Patient Safety. AB - This study looks to describe health care professionals' knowledge regarding patient safety. A quantitative study using questionnaires was conducted in three multi-disciplinary hospitals in Western Lithuania. Data were collected in 2014 from physicians, nurses, and nurse assistants. The overall results indicated quite a low level of safety knowledge, especially in regard to knowledge concerning general patient safety. The health care professionals' background factors such as their profession, education, the information about patient safety they were given during their vocational and continuing education, as well as their experience in their primary speciality seemed to be associated with several patient safety knowledge areas. Despite a wide variation in background factors, the knowledge level of respondents was generally found to be low. This requires that further research into health care professionals' safety knowledge related to specific issues such as medication, infection, falls, and pressure sore prevention should be undertaken in Lithuania. PMID- 26826141 TI - Environmental Resources in Maintenance of Physical Activity 6 Months Following Cardiac Rehabilitation. AB - This study examined differences in weekly time spent in physical activity by level of perceived environmental resources, 6 months following graduation from cardiac rehabilitation. A descriptive, longitudinal design used standardized measures to evaluate perceived environmental resources and physical activity levels. Repeated measures analysis of variance was used to examine mean differences in weekly time spent in physical activity by level of perceived environmental resources. Adults 51 to 86 years old (N = 150) diagnosed with coronary heart disease were included. There was a significant change over time in physical activity as measured by minutes per week, F(2, 148) = 7.915, p = .001, where activity increased between baseline and 3 months, and then dropped slightly at 6 months. This change over time differed by the level of perceived neighborhood resources, F(2, 148) = 3.545, p = .032. Home and neighborhood resources may positively influence physical activity maintenance following cardiac rehabilitation. PMID- 26826142 TI - Biogeography of thermophilic phototrophic bacteria belonging to Roseiflexus genus. AB - Isolated environments such as hot springs are particularly interesting for studying the microbial biogeography. These environments create an 'island effect' leading to genetic divergence. We studied the phylogeographic pattern of thermophilic anoxygenic phototrophic bacteria, belonging to the Roseiflexus genus. The main characteristic of the observed pattern was geographic and geochronologic fidelity to the hot springs within Circum-Pacific and Alpine Himalayan-Indonesian orogenic belts. Mantel test revealed a correlation between genetic divergence and geographic distance among the phylotypes. Cluster analysis revealed a regional differentiation of the global phylogenetic pattern. The phylogeographic pattern is in correlation with geochronologic events during the break up of Pangaea that led to the modern configuration of continents. To our knowledge this is the first geochronological scenario of intercontinental prokaryotic taxon divergence. The existence of the modern phylogeographic pattern contradicts with the existence of the ancient evolutionary history of the Roseiflexus group proposed on the basis of its deep-branching phylogenetic position. These facts indicate that evolutionary rates in Roseiflexus varied over a wide range. PMID- 26826143 TI - Forecasting and control policy assessment for the Ebola virus disease (EVD) epidemic in Sierra Leone using small-world networked model simulations. AB - OBJECTIVES: As the Ebola virus disease is still sustained in Sierra Leone, we analysed the epidemic for a recent period (21 December 2014 to 17 April 2015) using a small-world networked model and forecasted its evolution. Policy-control scenarios for the containment of the epidemic were also examined. METHODS: We developed an agent-based model with 6 million individuals (the population of Sierra Leone) interacting through a small-world social network. The model incorporates the main epidemiological factors, including the effect of burial practices to virus transmission. The effective reproductive number (Re) was evaluated directly from the agent-based simulations. Estimates of the epidemiological variables were computed on the basis of the official cases as reported by the Centers for Disease Control and Prevention (CDC). RESULTS: From 21 December 2014 to 18 February 2015 the epidemic was in recession compared with previous months, as indicated by the estimated Re of ~ 0.77 (95% CI 0.72 to 0.82). From 18 February to 17 April 2015, the Re rose above criticality (~ 1.98, 95% CI 1.33 to 2.22), flashing a note of caution for the situation. By projecting in time, we predicted that the epidemic would continue through July 2015. Our predictions were close to the cases reported by CDC by the end of June, verifying the criticality of the situation. In light of these developments, while revising our manuscript, we expanded our analysis to include the most recent data (until 15 August 2015). By mid-August, Re had fallen below criticality and the epidemic was expected to fade out by early December 2015. CONCLUSIONS: Our results call for the continuation of drastic control measures, which in the absence of an effective vaccine or therapy at present can only translate to isolation of the infected section of the population, to contain the epidemic. PMID- 26826144 TI - Trends in market share of leading cigarette brands in the USA: national survey on drug use and health 2002-2013. AB - OBJECTIVES: The main objective of this study is to examine trends in market share for leading cigarette brands, both before (2002-2008) and after (2009-2013) Food and Drug Administration (FDA) regulation of tobacco products.Design Data come from the annual National Survey on Drug Use and Health from 2002 through 2013. Descriptive statistics, cross tabulations, and logistic regression were employed. Data were weighted to the US population and adjusted for cigarette consumption. Our analysis is restricted to 164,343 current cigarette smokers who were at least 12 years of age or older, had smoked at least one cigarette in the 30 days prior to the survey, and reported a usual cigarette brand at the time of the survey. RESULTS: Over 12 years, 14 brands comprised over 77% of the cigarette market. Marlboro consistently held over 38% of the market. Newport held the second highest market share, and increased from 7.2% in 2002 to 10.9% by 2013. Market share of Pall Mall grew by over 400% (1.7% in 2002 vs 8.9% in 2013), likely aided by the 2009 Federal excise tax increase. No clear associations of changes in market share with the implementation of FDA's regulatory authority over tobacco in 2009 were noted. CONCLUSIONS: Tracking market share trends offers clues about brand marketing changing preferences of consumers. Rapidly growing cigarette brands should be monitored to determine if specific marketing practices or design changes are drivers, as these could represent public health concerns. Monitoring trends in cigarette market share could inform regulatory decision-making efforts related to marketing and advertising. PMID- 26826145 TI - Costs associated with implementation of a strict policy for controlling spread of highly resistant microorganisms in France. AB - OBJECTIVE: To assess costs associated with implementation of a strict 'search and isolate' strategy for controlling highly drug-resistant organisms (HDRO). DESIGN: Review of data from 2-year prospective surveillance (01/2012 to 12/2013) of HDRO. SETTING: Three university hospitals located in northern Paris. METHODS: Episodes were defined as single cases or outbreaks of glycopeptide-resistant enterococci (GRE) or carbapenemase-producing Enterobacteriacae (CPE) colonisation. Costs were related to staff reinforcement, costs of screening cultures, contact precautions and interruption of new admissions. Univariate analysis, along with simple and multiple linear regression analyses, was conducted to determine variables associated with cost of HDRO management. RESULTS: Overall, 41 consecutive episodes were included, 28 single cases and 13 outbreaks. The cost (mean +/- SD) associated with management of a single case identified within and/or 48 h after admission was ?4443 +/- 11,552 and ?11,445 +/- 15,743, respectively (p<0.01). In an outbreak, the total cost varied from ?14,864 +/- 17,734 for an episode with one secondary case (?7432 +/- 8867 per case) to ?136,525 +/- 151,231 (?12,845 +/- 5129 per case) when more than one secondary case occurred. In episodes of single cases, contact precautions and microbiological analyses represented 51% and 30% of overall cost, respectively. In outbreaks, cost related to interruption of new admissions represented 77-94% of total costs, and had the greatest financial impact (R(2)=0.98, p<0.01). CONCLUSIONS: In HDRO episodes occurring at three university hospitals, interruption of new admissions constituted the most costly measure in an outbreak situation. PMID- 26826146 TI - Association of restaurant smoking ban and the incidence of acute myocardial infarction in Finland. AB - OBJECTIVE: To describe the changes in nationwide acute myocardial infarction (AMI) incidence following the implementation of a law banning smoking indoors in restaurants on 1 June 2007. METHODS: Retrospective registry study of all hospitalisations for AMI in Finland. All 34,887 hospitalisations for AMI between 1 June 2005 and 31 May 2009 were identified from the Care Register for Health Care (CRHC) and statistics for tobacco consumption were obtained from the National Institute for Health and Welfare. Comorbidities for individual hospitalisations were searched from the CRHC. RESULTS: The incidence rate of AMI was reduced by 6.3% (95% CI 4.1% to 8.6%; p<0.0001) in the latter half of the study period following the smoking ban when adjusted for age, gender and overall population prevalence of smoking. Short-term incidence of AMI (6-month prior vs 6 months after the smoking ban) was also reduced (4.5%, 95% CI 0.2% to 9.0%; p=0.0399) and was largest in the working middle-aged group (40-50 years) but observed also in the oldest age group (>70 years). The incidence rates declined similarly for men and women. CONCLUSIONS: Banning indoor tobacco smoking in restaurants was associated with a mild additional reduction in AMI incidence on a nationwide level in Finland. PMID- 26826147 TI - Virtual online consultations: advantages and limitations (VOCAL) study. AB - INTRODUCTION: Remote video consultations between clinician and patient are technically possible and increasingly acceptable. They are being introduced in some settings alongside (and occasionally replacing) face-to-face or telephone consultations. METHODS: To explore the advantages and limitations of video consultations, we will conduct in-depth qualitative studies of real consultations (microlevel) embedded in an organisational case study (mesolevel), taking account of national context (macrolevel). The study is based in 2 contrasting clinical settings (diabetes and cancer) in a National Health Service (NHS) acute trust in London, UK. Main data sources are: microlevel--audio, video and screen capture to produce rich multimodal data on 45 remote consultations; mesolevel--interviews, ethnographic observations and analysis of documents within the trust; macrolevel- key informant interviews of national-level stakeholders and document analysis. Data will be analysed and synthesised using a sociotechnical framework developed from structuration theory. ETHICS APPROVAL: City Road and Hampstead NHS Research Ethics Committee, 9 December 2014, reference 14/LO/1883. PLANNED OUTPUTS: We plan outputs for 5 main audiences: (1) academics: research publications and conference presentations; (2) service providers: standard operating procedures, provisional operational guidance and key safety issues; (3) professional bodies and defence societies: summary of relevant findings to inform guidance to members; (4) policymakers: summary of key findings; (5) patients and carers: 'what to expect in your virtual consultation'. DISCUSSION: The research literature on video consultations is sparse. Such consultations offer potential advantages to patients (who are spared the cost and inconvenience of travel) and the healthcare system (eg, they may be more cost-effective), but fears have been expressed that they may be clinically risky and/or less acceptable to patients or staff, and they bring significant technical, logistical and regulatory challenges. We anticipate that this study will contribute to a balanced assessment of when, how and in what circumstances this model might be introduced. PMID- 26826148 TI - Qualitative focus group study investigating experiences of accessing and engaging with social care services: perspectives of carers from diverse ethnic groups caring for stroke survivors. AB - OBJECTIVES: Informal carers, often family members, play a vital role in supporting stroke survivors with post-stroke disability. As populations age, numbers of carers overall and those from minority ethnic groups in particular, are rising. Carers from all ethnic groups, but especially those from black and minority ethnic groups frequently fail to access support services, making understanding their experiences important. The study therefore explored the experiences of carers of stroke survivors aged 45+ years from 5 ethnic groups in accessing and receiving social care services after hospital discharge. DESIGN: This qualitative study used 7 recorded focus groups with informal carers of stroke survivors. Data were analysed thematically focusing on similarities and differences between ethnic groups. SETTING: Carers were recruited from voluntary sector organisations supporting carers, stroke survivors and black and minority ethnic groups in the UK. PARTICIPANTS: 41 carers from 5 ethnic groups (Asian Indian, Asian Pakistani, black African, black Caribbean, white British) participated in the focus groups. RESULTS: Several interconnected themes were identified including: the service gap between hospital discharge and home; carers as the best person to care and cultural aspects of caring and using services. Many themes were common to all the included ethnic groups but some related to specific groups. CONCLUSIONS: Across ethnic groups there were many similarities in the experiences of people caring for stroke survivors with complex, long-term care needs. Accessing services demands effort and persistence on carers' part. If carers believe services are unsatisfactory or that they, rather than formal services, should be providing support for stroke survivors, they are unlikely to persist in their efforts. Cultural and language differences add to the challenges black and minority ethnic group carers face. PMID- 26826149 TI - Qualitative evaluation of the Safety and Improvement in Primary Care (SIPC) pilot collaborative in Scotland: perceptions and experiences of participating care teams. AB - OBJECTIVES: To explore general practitioner (GP) team perceptions and experiences of participating in a large-scale safety and improvement pilot programme to develop and test a range of interventions that were largely new to this setting. DESIGN: Qualitative study using semistructured interviews. Data were analysed thematically. SUBJECTS AND SETTING: Purposive sample of multiprofessional study participants from 11 GP teams based in 3 Scottish National Health Service (NHS) Boards. RESULTS: 27 participants were interviewed. 3 themes were generated: (1) programme experiences and benefits, for example, a majority of participants referred to gaining new theoretical and experiential safety knowledge (such as how unreliable evidence-based care can be) and skills (such as how to search electronic records for undetected risks) related to the programme interventions; (2) improvements to patient care systems, for example, improvements in care systems reliability using care bundles were reported by many, but this was an evolving process strongly dependent on closer working arrangements between clinical and administrative staff; (3) the utility of the programme improvement interventions, for example, mixed views and experiences of participating in the safety climate survey and meeting to reflect on the feedback report provided were apparent. Initial theories on the utilisation and potential impact of some interventions were refined based on evidence. CONCLUSIONS: The pilot was positively received with many practices reporting improvements in safety systems, team working and communications with colleagues and patients. Barriers and facilitators were identified related to how interventions were used as the programme evolved, while other challenges around spreading implementation beyond this pilot were highlighted. PMID- 26826150 TI - How do doctors and nurses manage delirium in intensive care units? A qualitative study using focus groups. AB - OBJECTIVES: The aim of this study was to explore the experiences of doctors and nurses caring for patients with delirium in the intensive care unit (ICU) and to describe the process of delirium management. SETTING: This study was performed in 5 ICUs located within 4 hospitals in Madrid (Spain). PARTICIPANTS: Purposeful sampling was performed which included (1) doctors and nurses working in ICUs, (2) with >1 year experience in the ICU and (3) clinical experience with delirium. 38 professionals participated (19 doctors, 19 nurses), including 22 women and 16 men. The total mean age was 39 years. DESIGN: A qualitative study using focus groups. METHODS: 7 focus groups were held to collect data: 3 nurse focus groups, 3 doctor focus groups and 1 mixed focus group. Each group comprised 6-10 participants. A semistructured questions guide was used. Thematic analysis methods were used to analyse the data. RESULTS: 3 themes were identified: (1) the professional perspective on delirium; (2) implementing pharmacological and non pharmacological treatment for delirium and (3) work organisation in the ICU. The professionals regarded patients with delirium with uncertainty, and felt they were often underdiagnosed and poorly managed. Doctors displayed discrepancies regarding pharmacological prescriptions and decision-making. The choice of medication was determined by experience. Nurses felt that, for many doctors, delirium was not considered a matter of urgency in the ICU. Nurses encountered difficulties when applying verbal restraint, managing sleep disorders and providing early mobilisation. The lack of a delirium protocol generates conflicts regarding what type of care management to apply, especially during the night shift. A degree of group pressure exists which, in turn, influences the decision making process and patient care. CONCLUSIONS: Patients with delirium represent complex cases, requiring the implementation of specific protocols. These results serve to improve the process of care in patients with delirium. PMID- 26826151 TI - Improving the governance of patient safety in emergency care: a systematic review of interventions. AB - OBJECTIVES: To systematically review interventions that aim to improve the governance of patient safety within emergency care on effectiveness, reliability, validity and feasibility. DESIGN: A systematic review of the literature. METHODS: PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Database of Systematic Reviews and PsychInfo were searched for studies published between January 1990 and July 2014. We included studies evaluating interventions relevant for higher management to oversee and manage patient safety, in prehospital emergency medical service (EMS) organisations and hospital based emergency departments (EDs). Two reviewers independently selected candidate studies, extracted data and assessed study quality. Studies were categorised according to study quality, setting, sample, intervention characteristics and findings. RESULTS: Of the 18 included studies, 13 (72%) were non-experimental. Nine studies (50%) reported data on the reliability and/or validity of the intervention. Eight studies (44%) reported on the feasibility of the intervention. Only 4 studies (22%) reported statistically significant effects. The use of a simulation-based training programme and well-designed incident reporting systems led to a statistically significant improvement of safety knowledge and attitudes by ED staff and an increase of incident reports within EDs, respectively. CONCLUSIONS: Characteristics of the interventions included in this review (eg, anonymous incident reporting and validation of incident reports by an independent party) could provide useful input for the design of an effective tool to govern patient safety in EMS organisations and EDs. However, executives cannot rely on a robust set of evidence-based and feasible tools to govern patient safety within their emergency care organisation and in the chain of emergency care. Established strategies from other high-risk sectors need to be evaluated in emergency care settings, using an experimental design with valid outcome measures to strengthen the evidence base. PMID- 26826152 TI - Trauma teams and time to early management during in situ trauma team training. AB - OBJECTIVES: To investigate the association between the time taken to make a decision to go to surgery and gender, ethnicity, years in profession, experience of trauma team training, experience of structured trauma courses and trauma in the trauma team, as well as use of closed-loop communication and leadership styles during trauma team training. DESIGN: In situ trauma team training. The patient simulator was preprogrammed to represent a severely injured patient (injury severity score: 25) suffering from hypovolemia due to external trauma. SETTING: An emergency room in an urban Scandinavian level one trauma centre. PARTICIPANTS: A total of 96 participants were divided into 16 trauma teams. Each team consisted of six team members: one surgeon/emergency physician (designated team leader), one anaesthesiologist, one registered nurse anaesthetist, one registered nurse from the emergency department, one enrolled nurse from the emergency department and one enrolled nurse from the operating theatre. PRIMARY OUTCOME: HRs with CIs (95% CI) for the time taken to make a decision to go to surgery was computed from a Cox proportional hazards model. RESULTS: Three variables remained significant in the final model. Closed-loop communication initiated by the team leader increased the chance of a decision to go to surgery (HR: 3.88; CI 1.02 to 14.69). Only 8 of the 16 teams made the decision to go to surgery within the timeframe of the trauma team training. Conversely, call-outs and closed-loop communication initiated by the team members significantly decreased the chance of a decision to go to surgery, (HR: 0.82; CI 0.71 to 0.96, and HR: 0.23; CI 0.08 to 0.71, respectively). CONCLUSIONS: Closed-loop communication initiated by the leader appears to be beneficial for teamwork. In contrast, a high number of call-outs and closed-loop communication initiated by team members might lead to a communication overload. PMID- 26826153 TI - Disease severity of Shiga toxin-producing E. coli O157 and factors influencing the development of typical haemolytic uraemic syndrome: a retrospective cohort study, 2009-2012. AB - OBJECTIVES: Assess the disease severity of Shiga toxin-producing Escherichia coli (STEC) O157 infection and factors influencing the development of typical haemolytic uraemic syndrome (tHUS). DESIGN: A retrospective cohort study using data collected through routine surveillance questionnaires between 2009 and 2012. PARTICIPANTS: 3323 symptomatic cases of STEC O157. MAIN OUTCOME MEASURES: Incidence of human STEC O157 and tHUS, proportion of cases reporting bloody diarrhoea, hospitalisation, tHUS and death. Odds of progression to tHUS and predicted percentage chance of developing tHUS based on case demographics, STEC O157 strain characteristics and clinical symptoms. RESULTS: From 2009 to 2012, 3323 cases of symptomatic STEC O157 with completed questionnaires were reported, of which 172 developed tHUS (5.18%). Being aged 1-4 years (OR 8.65, 95% CI 5.01 to 14.94, p=0.004) or female (OR 1.61, 95% CI 1.12 to 2.30, p=0.009), being infected with phage type (PT) 21/28 (OR 2.07, 95% CI 1.25 to 3.42, p=0.005) or PT 2 (OR 2.18, 95% CI 1.06 to 4.50, p=0.034), receiving beta-lactam antibiotics (OR 4.08, 95% CI 1.43 to 11.68, p=0.009) and presenting with vomiting (OR 3.16, 95% CI 2.16 to 4.62, p<0.001) or bloody diarrhoea (OR 2.10, 95% CI 1.38 to 3.20, p=0.001) were found to be significant risk factors for progression to tHUS. The predicted percentage chance of developing tHUS varied from under 1% to 50% if all risk factors were present. CONCLUSIONS: The data from this study indicate the use of beta-lactam antibiotics should be avoided in suspected cases of STEC infection in all age groups, particularly in those under the age of 5. PMID- 26826155 TI - Do special constables in London feel that they are adequately prepared to meet their first aid responsibilities? A qualitative study. AB - OBJECTIVE: This study's aims were to explore the views of special constables in the London metropolitan police force concerning their obligations and skills as first aiders. BACKGROUND: The metropolitan police force provides police officers to act as first responders to emergency calls made by the public. Special constables act with the same powers and responsibility as police officers and are required to deal with incidents involving medical emergencies. SETTING: West London Police Station. PARTICIPANTS: Fifteen special constables entered and completed the study. METHODS AND OUTCOME MEASURES: A qualitative study involving semistructured interviews, participant observation, and reflective work. The outcome measures were the themes derived from the 'thematic framework approach' to analysis. RESULTS: Four main themes were identified. (1) 'Our responsibility?' -Special constables felt they had a responsibility, but were unsure of the origin of this responsibility, with many feeling it stemmed from public expectation. (2) 'Confidence'--Special constables had mixed feelings regarding their confidence in first aid scenarios and many felt that more could be done to improve their confidence. (3) 'Training needs'--Many felt the current training system was lacking in several ways including regularity, teaching and content. (4) 'Personal first aid knowledge'--Special constables were disappointed with their past performances. CONCLUSIONS: Owing to the small size of this study, the conclusions are limited; however, if the findings are confirmed by larger studies, they suggest the need to improve the confidence of special constables in first aid situations. PMID- 26826154 TI - Engaging patients through open notes: an evaluation using mixed methods. AB - OBJECTIVES: (A) To gain insights into the experiences of patients invited to view their doctors' visit notes, with a focus on those who review multiple notes; (B) to examine the relationships among fully transparent electronic medical records and quality of care, the patient-doctor relationship, patient engagement, self care, self-management skills and clinical outcomes. DESIGN: Mixed methods qualitative study: analyses of survey data, including content analysis of free text answers, and quantitative-descriptive measures combined with semistructured individual interviews, patient activation measures, and member checks. SETTING: Greater Boston, USA. PARTICIPANTS: Patients cared for by primary care physicians (PCPs) at the Beth Israel Deaconess Medical Center who had electronic access to their PCP visit notes. Among those submitting surveys, 576 free-text answers were identified and analysed (414 from female patients, 162 from male patients; 23-88 years). In addition, 13 patients (9 female, 4 male; 58-87 years) were interviewed. RESULTS: Patient experiences indicate improved understanding (of health information), better relationships (with doctors), better quality (adherence and compliance; keeping track) and improved self-care (patient centredness, empowerment). Patients want more doctors to offer access to their notes, and some wish to contribute to their generation. Those patients with repeated experience reviewing notes express fewer concerns and more perceived benefits. CONCLUSIONS: As the use of fully transparent medical records spreads, it is important to gain a deeper understanding of possible benefits or harms, and to characterise target populations that may require varying modes of delivery. Patient desires for expansion of this practice extend to specialty care and settings beyond the physician's office. Patients are also interested in becoming involved actively in the generation of their medical records. The OpenNotes movement may increase patient activation and engagement in important ways. PMID- 26826156 TI - Comparative effectiveness of sodium-glucose co-transporter 2 inhibitors for controlling hyperglycaemia in patients with type 2 diabetes: protocol for a systematic review and network meta-analysis. AB - INTRODUCTION: As a new class of glucose-lowering drugs, sodium-glucose co transporter 2 (SGLT2) inhibitors are effective for controlling hyperglycaemia, however, the relative effectiveness and safety of 6 recently available SGLT2 inhibitors have rarely been studied. Therefore, we aim to perform pairwise comparisons of the 6 SGLT2 inhibitors. METHODS AND ANALYSIS: A systematic review and network meta-analysis will be conducted. Clinical studies that examine effectiveness and safety of either canagliflozin, dapagliflozin, empagliflozin, ipragliflozin, tofogliflozin or luseogliflozin will be included. These studies will be systematically retrieved in MEDLINE, EMBASE and the Cochrane Library, from inception to November 2015. Two reviewers will independently screen for eligible studies and then extract data from the studies as well as assess risk of bias. Discrepancies in screening and data extraction will be arbitrated by a third reviewer. A traditional meta-analysis will be performed to combine the effect sizes calculated from head-to-head comparisons with a random effect model. The effect sizes computed from indirect comparisons will be further combined in a network meta-analysis. Heterogeneity will be tested with the Cochrane's Q statistic, and publication bias will be assessed using a funnel plot and the Egger's test. ETHICS AND DISSEMINATION: Relative effectiveness and harms of the 6 SGLT2 inhibitors will be demonstrated through this systematic review and network meta-analysis. The result of the review will be disseminated through a peer review journal and conference presentations. Patients, clinicians and policymakers will benefit from this review in selecting a SGLT2 inhibitor for glucose control in patients with type 2 diabetes. TRIAL REGISTRATION NUMBER: PROSPERO CRD42015025981. PMID- 26826157 TI - Chiba study of Mother and Children's Health (C-MACH): cohort study with omics analyses. AB - PURPOSE: Recent epidemiological studies have shown that environmental factors during the fetal period to early childhood might affect the risk of non communicable diseases in adulthood. This is referred to as the developmental origins of health and disease (DOHaD) concept. The Chiba study of Mother and Children's Health (C-MACH) is a birth cohort study based on the DOHaD hypothesis and involves multiomics analysis. This study aims to explore the effects of genetic and environmental factors--particularly the fetal environment and postbirth living environment--on children's health, and to identify potential biomarkers for these effects. PARTICIPANTS: The C-MACH consists of three hospital based cohorts. The study participants are pregnant women at <13 weeks gestation. Women who underwent an examination in one of the three hospitals received an explanation of the study. The participants consented to completing questionnaire surveys and the collection and storage of biological and house/environmental samples. Participants were provided unique study numbers. All of the data and biological specimens will be stored in the Chiba University Center for Preventive Medical Sciences and Chiba University Center for Preventive Medical Sciences BioBank, respectively. FINDINGS TO DATE: Consent to participate was obtained from 433 women. Of these women, 376 women completed questionnaires in the early gestational period. The mean age was 32.5 (4.4) years. The mean body mass index (BMI) was 21.1 (3.0) kg/m(2). Before pregnancy, 72.3% of the women had a BMI of 18.5-24.9 kg/m(2). During early pregnancy, 5.0% of the participants smoked. FUTURE PLANS: Primary outcomes are allergy, obesity, endocrine and metabolic disorders, and developmental disorders. Genome-level, metabolome-level, umbilical cord DNA methylation (epigenome), gut microbiota and environmental chemical exposure variables will be evaluated. We will analyse the relationships between the outcomes and analytical variables. PMID- 26826158 TI - Immune reconstitution inflammatory syndrome versus non-immune reconstitution inflammatory syndrome lymphoma in HIV patients on antiretroviral therapy. AB - Little is known about differences between immune reconstitution inflammatory syndrome (IRIS) and non-IRIS lymphoma in HIV patients on antiretroviral therapy (ART). The aim of this study was to describe the characteristics of IRIS and non IRIS lymphoma in Korean HIV-positive patients on ART compared with lymphoma in those off ART. Of 1490 patients, 41 (3%) had lymphoma. Of these, 27 cases (66%) were classified as lymphoma off ART, eight as IRIS lymphoma, and six as non-IRIS lymphoma on ART. Hodgkin lymphoma was significantly more common among patients with non-IRIS lymphoma on ART than among those with lymphoma off ART (P = 0.005), whereas there was no Hodgkin lymphoma among IRIS lymphoma. Stage IV lymphoma was significantly rarer in non-IRIS lymphoma on ART than in lymphoma off ART (P = 0.007). Non-IRIS lymphoma on ART tends to have a better survival rate than lymphoma off ART (Kaplan-Meier survival analysis, P = 0.167), while IRIS lymphoma exhibited a survival rate similar to lymphoma off ART (P = 0.618). In Korean HIV positive patients, there were significantly more cases of Hodgkin lymphoma of a less advanced stage in non-IRIS lymphoma on ART than in lymphoma off ART, in contrast to IRIS lymphoma. PMID- 26826159 TI - Prevalence of hepatitis C virus infection among HIV+ men who have sex with men: a systematic review and meta-analysis. AB - Since 2000, an increase in hepatitis C virus infection among HIV-infected (HIV+) men who have sex with men has been observed. Evidence points to blood exposure during sex as the medium of hepatitis C virus transmission. Hepatitis C virus prevalence among HIV + MSM overall and in relation to injection drug use is poorly characterized. In this study, a systematic review and meta-analysis examining global hepatitis C virus antibody prevalence and estimating active hepatitis C virus prevalence among HIV + MSM were conducted; 42 reports provided anti-hepatitis C virus prevalence data among HIV + MSM. Pooled prevalence produced an overall anti-hepatitis C virus prevalence among HIV + MSM of 8.1%; active HCV prevalence estimate was 5.3%-7.3%. Anti-hepatitis C virus prevalence among injection drug use and non-injection drug use HIV + MSM was 40.0% and 6.7%, respectively. Among HIV + MSM, hepatitis C virus prevalence increased significantly over time among the overall and non-injection drug use groups, and decreased significantly among injection drug use HIV + MSM. We identified a moderate prevalence of hepatitis C virus among all HIV + MSM and among non injection drug use HIV + MSM; for both, prevalence was observed to be increasing slightly. Pooled prevalence of hepatitis C virus among HIV + MSM was higher than that observed in the 1945-1965 US birth cohort. The modest but rising hepatitis C virus prevalence among HIV + MSM suggests an opportunity to control HCV among HIV + MSM; this combined with data demonstrating a rising hepatitis C virus incidence highlights the temporal urgency to do so. PMID- 26826160 TI - HIV self-testing in Peru: questionable availability, high acceptability but potential low linkage to care among men who have sex with men and transgender women. AB - HIV status awareness is key to prevention, linkage-to-care and treatment. Our study evaluated the accessibility and potential willingness of HIV self-testing among men who have sex with men (MSM) and transgender women in Peru. We surveyed four pharmacy chains in Peru to ascertain the commercial availability of the oral HIV self-test. The pharmacies surveyed confirmed that HIV self-test kits were available; however, those available were not intended for individual use, but for clinician use. We interviewed 147 MSM and 45 transgender women; nearly all (82%) reported willingness to perform the oral HIV self-test. However, only 55% of participants would definitely seek a confirmatory test in a clinic after an HIV positive test result. Further, price may be a barrier, as HIV self-test kits were available for 18 USD, and MSM and transgender women were only willing to pay an average of 5 USD. HIV self-testing may facilitate increased access to HIV testing among some MSM/transgender women in Peru. However, price may prevent use, and poor uptake of confirmatory testing may limit linkage to HIV treatment and care. PMID- 26826161 TI - Prevalence of Mycoplasma genitalium in men with urethritis and in high risk asymptomatic males in Tel Aviv: a prospective study. AB - We sought to investigate the prevalence of Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis in men presenting to a sexually transmitted infection (STI) clinic, with special attention to M. genitalium, its occurrence in Israeli patients, coinfections, and risk factors. In a cross-sectional study, 259 men were successively enrolled in the Tel Aviv Levinsky Clinic for STIs between November 2008 and November 2010. There were 118 men with urethritis and 141 high-risk men without symptoms. M. genitalium, C. trachomatis, N. gonorrhoeae, and T. vaginalis were detected using nucleic acid amplification tests. Demographic characteristics and risk factors were documented. The overall prevalence of infection with M. genitalium, C. trachomatis, N. gonorrhoeae, and T. vaginalis, were 6.6%, 12.7%, 23.1%, and 0%, respectively. Prevalences in men with urethritis were 11.9%, 22%, and 49%, for M. genitalium, C. trachomatis, and N. gonorrhoeae, respectively. Prevalences in men without symptoms were 2.1%, 5.0%, and 1.4%, for M. genitalium, C. trachomatis, and N. gonorrhoeae, respectively. Co-infections were found only in symptomatic individuals, in whom 5.9% were infected concomitantly with C. trachomatis and N. gonorrhoeae, and 2.5% had dual infection with M. genitalium and N. gonorrhoeae. N. gonorrhoeae, C. trachomatis, and M. genitalium were significantly more prevalent in patients with urethritis. M. genitalium was significantly more prevalent in the heterosexual population than in homosexual males. To conclude, we have found that M. genitalium infection is associated with urethritis in Israeli men, and more so in the heterosexual population. Testing men for M. genitalium as a cause of non-gonococcal urethritis is warranted, particularly because of its poor response to doxycycline and possible failure of azithromycin. PMID- 26826162 TI - A Detailed Assessment of Varying Ejection Rate on Delivery Efficiency of Mesenchymal Stem Cells Using Narrow-Bore Needles. AB - As the number of clinical trials exploring cell therapy rises, a thorough understanding of the limits of cell delivery is essential. We used an extensive toolset comprising various standard and multiplex assays for the assessment of cell delivery postejection. Primary human mesenchymal stem cell (hMSC) suspensions were drawn up into 100-ul Hamilton syringes with 30- and 34-gauge needles attached, before being ejected at rates ranging from 10 to 300 ul/minute. Effects of ejection rate, including changes in viability, apoptosis, senescence, and other key aspects of cellular health, were evaluated. Ejections at slower flow rates resulted in a lower percentage of the cell dose being delivered, and apoptosis measurements of samples ejected at 10 ul/minute were significantly higher than control samples. Immunophenotyping also revealed significant downregulation of CD105 expression in samples ejected at 10 ul/minute (p < .05). Differentiation of ejected hMSCs was investigated using qualitative markers of adipogenesis, osteogenesis, and chondrogenesis, which revealed that slower ejection rates exerted a considerable effect upon the differentiation capacity of ejected cells, thereby possibly influencing the success of cell-based therapies. The findings of this study demonstrate that ejection rate has substantial impact on the percentage of cell dose delivered and cellular health postejection. PMID- 26826163 TI - Alginate-Encapsulation for the Improved Hypothermic Preservation of Human Adipose Derived Stem Cells. AB - Despite considerable progress within the cell therapy industry, unmet bioprocessing and logistical challenges associated with the storage and distribution of cells between sites of manufacture and the clinic exist. We examined whether hypothermic (4 degrees C-23 degrees C) preservation of human adipose-derived stem cells could be improved through their encapsulation in 1.2% calcium alginate. Alginate encapsulation improved the recovery of viable cells after 72 hours of storage. Viable cell recovery was highly temperature-dependent, with an optimum temperature of 15 degrees C. At this temperature, alginate encapsulation preserved the ability for recovered cells to attach to tissue culture plastic on rewarming, further increasing its effect on total cell recovery. On attachment, the cells were phenotypically normal, displayed normal growth kinetics, and maintained their capacity for trilineage differentiation. The number of cells encapsulated (up to 2 * 10(6) cells per milliliter) did not affect viable cell recovery nor did storage of encapsulated cells in a xeno-free, serum-free,current Good Manufacturing Practice-grade medium. We present a simple, low-cost system capable of enhancing the preservation of human adipose-derived stem cells stored at hypothermic temperatures, while maintaining their normal function. The storage of cells in this manner has great potential for extending the time windows for quality assurance and efficacy testing, distribution between the sites of manufacture and the clinic, and reducing the wastage associated with the limited shelf life of cells stored in their liquid state. PMID- 26826164 TI - Whole exome sequencing in recurrent early pregnancy loss. AB - STUDY HYPOTHESIS: Exome sequencing can identify genetic causes of idiopathic recurrent pregnancy loss (RPL). STUDY FINDING: We identified compound heterozygous deleterious mutations affecting DYNC2H1 and ALOX15 in two out of four families with RPL. Both genes have a role in early development. Bioinformatics analysis of all genes with rare and putatively pathogenic mutations in miscarriages and couples showed enrichment in pathways relevant to pregnancy loss, including the complement and coagulation cascades pathways. WHAT IS KNOWN ALREADY: Next generation sequencing (NGS) is increasingly being used to identify known and novel gene mutations in children with developmental delay and in fetuses with ultrasound-detected anomalies. In contrast, NGS is rarely used to study pregnancy loss. Chromosome microarray analysis detects putatively causative DNA copy number variants (CNVs) in ~2% of miscarriages and CNVs of unknown significance (predominantly parental in origin) in up to 40% of miscarriages. Therefore, a large number of miscarriages still have an unknown cause. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Whole exome sequencing (WES) was performed using Illumina HiSeq 2000 platform on seven euploid miscarriages from four families with RPL. Golden Helix SVS v8.1.5 was used for data assessment and inheritance analysis for deleterious DNA variants predicted to severely disrupt protein-coding genes by introducing a frameshift, loss of the stop codon, gain of the stop codon, changes in splicing or the initial codon. Webgestalt (http://bioinfo.vanderbilt.edu/webgestalt/) was used for pathway and disease association enrichment analysis of a gene pool containing putatively pathogenic variants in miscarriages and couples in comparison to control gene pools. MAIN RESULTS AND THE ROLE OF CHANCE: Compound heterozygous mutations in DYNC2H1 and ALOX15 were identified in miscarriages from two families with RPL. DYNC2H1 is involved in cilia biogenesis and has been associated with fetal lethality in humans. ALOX15 is expressed in placenta and its dysregulation has been associated with inflammation, placental, dysfunction, abnormal oxidative stress response and angiogenesis. The pool of putatively pathogenic single nucleotide variants (SNVs) and small insertions and deletions (indels) detected in the miscarriages showed enrichment in 'complement and coagulation cascades pathway', and 'ciliary motility disorders'. We conclude that CNVs, individual SNVs and pool of deleterious gene mutations identified by exome sequencing could contribute to RPL. LIMITATIONS, REASONS FOR CAUTION: The size of our sample cohort is small. The functional effect of candidate mutations should be evaluated to determine whether the mutations are causative. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to assess whether SNVs may contribute to the pathogenesis of miscarriage. Furthermore, our findings suggest that collective effect of mutations in relevant biological pathways could be implicated in RPL. STUDY FUNDING AND COMPETING INTERESTS: The study was funded by Canadian Institutes of Health Research (grant MOP 106467) and Michael Smith Foundation of Health Research Career Scholar salary award to ERS. PMID- 26826165 TI - Expanding Therapy for Neuroendocrine Tumors. PMID- 26826166 TI - Adult and childhood weight influence body image and depression through weight stigmatization. AB - The goal of this study was to examine lifetime weight stigmatization as a mediator of the relationships among current body mass index, childhood overweight, depression, and body dissatisfaction. Participants were 299 female undergraduates (mean age = 20.52, standard deviation = 2.57; mean body mass index = 23.29, standard deviation = 4.51). Weight stigmatization significantly mediated the relationships between body mass index and body dissatisfaction, body mass index and depressive symptoms, and childhood overweight and depressive symptoms. The model accounted for 44.7 percent of the variance in depressive symptoms and 28.2 percent of the variance in body image dissatisfaction. Findings indicated that a decrease in weight stigmatization may predict better mental health. PMID- 26826167 TI - Brief report: Compensatory health beliefs are negatively associated with intentions for regular fruit and vegetable consumption when self-efficacy is low. AB - Compensatory health beliefs (the beliefs that an unhealthy behaviour can be compensated by a healthy behaviour) can interfere with adherence to fruit and vegetable consumption recommendations. Fruit and vegetable consumption, social cognitive variables and compensatory health beliefs were investigated via self report at baseline (T0) and 8-week follow-up (T1) in N = 790 participants. Self efficacy predicted fruit and vegetable consumption intentions. Planning mediated between intentions and T1 fruit and vegetable consumption. Compensatory health beliefs negatively predicted intentions at low self-efficacy levels only. The results propose the use of self-efficacy interventions to diminish the negative effects of compensatory health beliefs when forming fruit and vegetable consumption intentions and foster planning to translate intentions into behaviour. PMID- 26826168 TI - One-year effects of Project EX: A smoking intervention pilot program with Spanish adolescents. AB - Adolescent smoking is a major public health problem, which has led to the development of cessation programs such as Project EX. However, there is no evidence for the long-term efficacy of cessation among Spanish adolescents. This study provides a 1-year follow-up evaluation of the Project EX tobacco use cessation program among 211 smokers. The intent-to-treat 30-day smoking quit rate for the program group was 7.81 percent ( p = .04), whereas no smokers quit in the control group ( p = .02). The intervention had a significant influence on future smoking expectation, intention, motivation to quit, and overall level of 30-day smoking. Long-term outcomes of the Project EX clinic-based program are promising for adolescent smokers in Spain. PMID- 26826169 TI - Type D personality: Application of DS14 French version in general and clinical populations. AB - The aim of this study was to validate the French-language version of the Type D personality scale-14 among general and clinical populations (acute coronary syndrome and breast cancer patients). The two-factor structure of the Type D personality scale-14 was confirmed by factorial and confirmatory analyses. Internal consistency for both subdimensions of Type D personality scale-14 (negative affectivity and social inhibition) was very good with alpha = .87 for each. Contrary to our expectations, the Type D prevalence was much higher in the breast cancer group than in the acute coronary syndrome patients. In conclusion, the French-language Type D personality scale-14 showed good psychometric properties among general and clinical populations. PMID- 26826170 TI - Early recurrence of atrial fibrillation after catheter ablation with left atrial fibrosis identified at cardiac magnetic resonance by late gadolinium enhancement. AB - In patients with atrial fibrillation (AF), extensive atrial tissue fibrosis identified by delayed enhancement magnetic resonance imaging has been associated with early recurrence of AF after catheter ablation. We present a case of a patient with extensive atrial fibrosis and AF recurrence.The study of late gadolinium enhancement with cardiac magnetic resonance imaging in patients with AF could be a valuable noninvasive tool for the selection of patients suitable for successful catheter ablation. PMID- 26826171 TI - Going home after infant cardiac surgery: a UK qualitative study. AB - OBJECTIVE: To qualitatively assess the discharge processes and postdischarge care in the community for infants discharged after congenital heart interventions in the first year of life. DESIGN: Qualitative study using semistructured interviews and Framework Analysis. SETTING: UK specialist cardiac centres and the services their patients are discharged to. SUBJECTS: Twenty-five cardiologists and nurses from tertiary centres, 11 primary and secondary health professionals and 20 parents of children who had either died after discharge or had needed emergency readmission. RESULTS: Participants indicated that going home with an infant after cardiac intervention represents a major challenge for parents and professionals. Although there were reported examples of good care, difficulties are exacerbated by inconsistent pathways and potential loss of information between the multiple teams involved. Written documentation from tertiary centres frequently lacks crucial contact information and contains too many specialist terms. Non-tertiary professionals and parents may not hold the information required to respond appropriately when an infant deteriorates, this contributing to the stressful experience of managing these infants at home. Where they exist, the content of formal 'home monitoring pathways' varies nationally, and families can find this onerous. CONCLUSIONS: Service improvements are needed for infants going home after cardiac intervention in the UK, focusing especially on enhancing mechanisms for effective transfer of information outside the tertiary centre and processes to assist with monitoring and triage of vulnerable infants in the community by primary and secondary care professionals. At present there is no routine audit for this stage of the patient journey. PMID- 26826172 TI - Skills retention in Sudanese village midwives 1 year following Helping Babies Breathe training. AB - BACKGROUND: Over 80% of deliveries in Sudan occur in isolated villages, attended by village midwives (VMWs). Upgrading newborn resuscitation skills with the Helping Babies Breathe (HBB) programme could improve newborn survival rates. OBJECTIVE: To describe the competencies in newborn resuscitation of selected VMWs pre-HBB and post-HBB training. METHODS: In a prospective intervention study, the VMWs' performances in the HBB Objective Structured Clinical Examination B simulated scenario (manikin requiring face-mask ventilation (FMV)) were digitally recorded and analysed prior to and 3 and 12 months following HBB training. Regular manikin-based practice was encouraged following training. RESULTS: Pre HBB training, 42% of 71 VMWs (of whom 61% were functionally illiterate) stimulated the non-breathing manikin by holding it by the legs and either stimulated/slapped (30.4%) or shook (12.7%) it, while 25% (18/71) provided manikin mouth-to-mouth ventilation. The low scorings on the 'preparation for birth' (0% and 3.1% at 3 and 12 months, respectively) were mainly due to failure to demonstrate the subitem of 'cleans hands'. The percentage of VMWs providing manikin FMV within the Golden Minute increased from 37.3% (25/67) to 72.3% (47/65) (p<0.005), but there were no significant differences in the number of VMWs producing at least five FMVs at 3 months (73%, 49/67) and 12 months (58%, 38/65), respectively. CONCLUSIONS: VMWs, despite a high illiteracy rate, absorbed and sustained HBB skills for at least a year. Regular, low intensity, manikin based skills training with peers may have helped sustain FMV, but not hand cleansing skills. PMID- 26826173 TI - Adolescent medicine in the USA: a perspective on progress and lessons learnt. PMID- 26826174 TI - Hearing outcome of infants with congenital cytomegalovirus and hearing impairment. AB - BACKGROUND: Congenital cytomegalovirus (cCMV) is the most common non-genetic cause of childhood sensorineural hearing loss. Antiviral treatment has been shown to prevent hearing deterioration in these infants. However, studies focused on infants with hearing impairment at birth and on the specific degree of impairment and further improvement or deterioration are lacking. OBJECTIVE: To investigate the relationship between hearing status at birth and any change in hearing status at the end of a prolonged follow-up period, after receiving 12 months of antiviral treatment in children born with hearing impairment due to congenital cCMV. METHODS: Clinical, laboratory, radiological and audiological data of all infants with cCMV infection followed in our centre between 2005 and 2013 were reviewed. Treatment with antiviral medication for hearing impairment found during the neonatal period was12 months of gan/valganciclovir. Hearing studies were performed only on infants who had been followed up for more than 1 year after treatment. RESULTS: Hearing impairment at birth was found in 54 (36.2%) of the 149 infants diagnosed with symptomatic cCMV, and found in 77 affected ears; unilateral in 31 (57.4%) and bilateral in 23 (42.6%). After 1 year of antiviral treatment and a long-term follow-up of the 77 affected ears at baseline, 50 (64.9%) had improved, 22 (28.6%) remained unchanged and 5 (6.5%) had deteriorated. Most improved ears (38/50=76%) returned to normal hearing. Improvement was most likely to occur in infants born with mild or moderate hearing loss and less in those with severe impairment. CONCLUSIONS: We found that infants born with cCMV and hearing impairment, receiving 12 months of antiviral treatment, showed significant improvement in hearing status. The probability of hearing improvement seems inversely related to the severity of the impairment at birth. PMID- 26826175 TI - Early weight gain and diabetes. PMID- 26826176 TI - Structure-Function Analysis of Mammalian CYP2B Enzymes Using 7-Substituted Coumarin Derivatives as Probes: Utility of Crystal Structures and Molecular Modeling in Understanding Xenobiotic Metabolism. AB - Crystal structures of CYP2B35 and CYP2B37 from the desert woodrat were solved in complex with 4-(4-chlorophenyl)imidazole (4-CPI). The closed conformation of CYP2B35 contained two molecules of 4-CPI within the active site, whereas the CYP2B37 structure demonstrated an open conformation with three 4-CPI molecules, one within the active site and the other two in the substrate access channel. To probe structure-function relationships of CYP2B35, CYP2B37, and the related CYP2B36, we tested the O-dealkylation of three series of related substrates namely, 7-alkoxycoumarins, 7-alkoxy-4-(trifluoromethyl)coumarins, and 7-alkoxy-4 methylcoumarins-with a C1-C7 side chain. CYP2B35 showed the highest catalytic efficiency (kcat/KM) with 7-heptoxycoumarin as a substrate, followed by 7 hexoxycoumarin. In contrast, CYP2B37 showed the highest catalytic efficiency with 7-ethoxy-4-(trifluoromethyl)coumarin (7-EFC), followed by 7-methoxy-4 (trifluoromethyl)coumarin (7-MFC). CYP2B35 had no dealkylation activity with 7 MFC or 7-EFC. Furthermore, the new CYP2B-4-CPI-bound structures were used as templates for docking the 7-substituted coumarin derivatives, which revealed orientations consistent with the functional studies. In addition, the observation of multiple -Cl and -NH-pi interactions of 4-CPI with the aromatic side chains in the CYP2B35 and CYP2B37 structures provides insight into the influence of such functional groups on CYP2B ligand binding affinity and specificity. To conclude, structural, computational, and functional analysis revealed striking differences between the active sites of CYP2B35 and CYP2B37 that will aid in the elucidation of new structure-activity relationships. PMID- 26826177 TI - The short-term cost of falls, poisonings and scalds occurring at home in children under 5 years old in England: multicentre longitudinal study. AB - BACKGROUND: Childhood falls, poisonings and scalds, occurring predominantly in the home, are an important public health problem, yet there is limited evidence on the costs of these injuries to individuals and society. OBJECTIVES: To estimate National Health Service (NHS) and child and family costs of falls, poisonings and scalds. METHODS: We undertook a multicentre longitudinal study of falls, poisonings and scalds in children under 5 years old, set in acute NHS Trusts across four UK study centres. Data from parental self-reported questionnaires on health service resource use, family costs and expenditure were combined with unit cost data from published sources to calculate average cost for participants and injury mechanism. RESULTS: 344 parents completed resource use questionnaires until their child recovered from their injury or until 12 months, whichever came soonest. Most injuries were minor, with >95% recovering within 2 weeks, and 99% within 1 month of the injury. 61% emergency department (ED) attendees were not admitted, 35% admitted for <=1 day and 4% admitted for >=2 days. The typical healthcare cost of an admission for >=2 days was estimated at L2000-3000, for an admission for <=1 day was L700-1000 and for an ED attendance without admission was L100-180. Family costs were considerable and varied across injury mechanisms. Of all injuries, scalds accrued highest healthcare and family costs. CONCLUSIONS: Falls, poisonings and scalds incur considerable short-term healthcare and family costs. These data can inform injury prevention policy and commissioning of preventive services. PMID- 26826178 TI - Use of Core Correctional Practice and Inmate Preparedness for Release. AB - Core correctional practices (CCP) are an evidence-based approach that can improve the quality of the prison environment and enhance prisoner outcomes. CCP focus on increasing the effectiveness of treatment interventions as well as the therapeutic potential of relationships between prisoners and correctional staff. This study utilizes a new survey-based measurement tool to assess inmate perceptions of the quality of service delivery and level of adherence to CCP. It then examines the relationship between perceptions of CCP and prisoner's preparedness for releasing using both bivariate and multivariate analyses. The results show that the perceptions of CCP are positively correlated with readiness for release and are the most powerful predictor of readiness for release in the multivariate models. Implications for the future operationalization of CCP and its role in prisoner reentry are discussed. PMID- 26826179 TI - Acute Limb Ischemia and Outcomes With Vorapaxar in Patients With Peripheral Artery Disease: Results From the Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis in Myocardial Infarction 50 (TRA2 degrees P-TIMI 50). AB - BACKGROUND: Patients with peripheral artery disease (PAD) are at heightened risk of acute limb ischemia (ALI), a morbid event that may result in limb loss. We investigated the causes, sequelae, and predictors of ALI in a contemporary population with symptomatic PAD and whether protease-activated receptor 1 antagonism with vorapaxar reduced ALI overall and by type. METHODS AND RESULTS: The Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis in Myocardial Infarction 50 (TRA2 degrees P-TIMI 50) was a randomized, double-blind, placebo-controlled trial of vorapaxar in stable patients, including 3787 with symptomatic PAD. ALI was a prespecified adjudicated end point using a formal definition. A total of 150 ALI events occurred in 108 patients during follow-up (placebo 3-year rate, 3.9%; 1.3% annualized). For patients with symptomatic PAD, previous peripheral revascularization, smoking, and the ankle-brachial index were predictive of ALI. The majority of ALI events occurred as a result of surgical graft thrombosis (56%), followed by native vessel in situ thrombosis (27%). Stent thrombosis and thromboembolism caused ALI in 13% and 5%, respectively. Amputation occurred in 17.6% presenting with ALI. Vorapaxar reduced first ALI events by 41% (hazard ratio, 0.58; 95% confidence interval, 0.39-0.86; P=0.006) and total ALI events by 41% (94 versus 56 events; risk ratio, 0.59; 95% confidence interval, 0.38-0.93; P=0.022). The efficacy of vorapaxar was consistent across types of ALI. CONCLUSIONS: In selected patients with symptomatic PAD and without atrial fibrillation, ALI occurs at a rate of 1.3%/y, is most frequently caused by acute bypass graft thrombosis or in situ thrombosis of a diseased vessel, and often results in limb loss. Vorapaxar reduces ALI in patients with symptomatic PAD with consistency across type, including PAD resulting from surgical graft thrombosis and in-situ thrombosis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00526474. PMID- 26826180 TI - Sphingosine-1-Phosphate Receptor Agonist Fingolimod Increases Myocardial Salvage and Decreases Adverse Postinfarction Left Ventricular Remodeling in a Porcine Model of Ischemia/Reperfusion. AB - BACKGROUND: Fingolimod, a sphingosine-1-phosphate receptor agonist, is used for the treatment of multiple sclerosis and exerts antiapoptotic properties. We hypothesized that sphingosine-1-phosphate receptor activation with fingolimod during acute myocardial infarction (MI) inhibits apoptosis, leading to increased myocardial salvage, reduced infarct size, and mitigated left ventricular (LV) remodeling in a porcine model of ischemia/reperfusion. METHODS AND RESULTS: Ischemia/reperfusion was induced in pigs by balloon occlusion of the left anterior descending artery, followed by reperfusion. Animals randomly received fingolimod or saline (control). In short-term experiments, fingolimod treatment activated the cardioprotective reperfusion injury salvage kinase and survivor activating factor enhancement pathways in the infarct border zone 24 hours after MI, leading to decreased cardiomyocyte apoptosis and reduced myocardial oxidative stress. These effects were abolished by specific inhibitors of both pathways, demonstrating that fingolimod-induced cardioprotection was mediated by reperfusion injury salvage kinase and survivor activating factor enhancement pathways. In long-term experiments, fingolimod significantly improved myocardial salvage, reduced infarct size, and improved systolic LV function measured by cardiac magnetic resonance 1 week and 1 month after MI. Importantly, fingolimod mitigated the development of adverse post-MI LV remodeling 1 month after MI. Specifically, fingolimod treatment led to a significant reduction in LV mass, LV dilatation, and neurohormonal activation, and it preserved LV geometry. Furthermore, fingolimod decreased interstitial fibrosis, cardiomyocyte hypertrophy, and chronic activation of Akt and extracellular receptor kinase 1/2 in the remote noninfarcted myocardium. CONCLUSIONS: Sphingosine-1-phosphate receptor activation with fingolimod during acute MI reduced infarct size via the reperfusion injury salvage kinase and survivor activating factor enhancement pathways, improved systolic LV function, and mitigated post-MI LV remodeling. Our data strongly support a cardioprotective role for sphingosine-1-phosphate receptor activation during MI. PMID- 26826181 TI - Long-Term Outcome of Patients With Chronic Thromboembolic Pulmonary Hypertension: Results From an International Prospective Registry. AB - BACKGROUND: Chronic thromboembolic pulmonary hypertension, a rare complication of acute pulmonary embolism, is characterized by fibrothrombotic obstructions of large pulmonary arteries combined with small-vessel arteriopathy. It can be cured by pulmonary endarterectomy, and can be clinically improved by medical therapy in inoperable patients. A European registry was set up in 27 centers to evaluate long-term outcome and outcome correlates in 2 distinct populations of operated and not-operated patients who have chronic thromboembolic pulmonary hypertension. METHODS AND RESULTS: A total of 679 patients newly diagnosed with chronic thromboembolic pulmonary hypertension were prospectively included over a 24-month period. Estimated survival at 1, 2, and 3 years was 93% (95% confidence interval [CI], 90-95), 91% (95% CI, 87-93), and 89% (95% CI, 86-92) in operated patients (n=404), and only 88% (95% CI, 83-91), 79% (95% CI, 74-83), and 70% (95% CI, 64 76) in not-operated patients (n=275). In both operated and not-operated patients, pulmonary arterial hypertension-targeted therapy did not affect survival estimates significantly. Mortality was associated with New York Heart Association functional class IV (hazard ratio [HR], 4.16; 95% CI, 1.49-11.62; P=0.0065 and HR, 4.76; 95% CI, 1.76-12.88; P=0.0021), increased right atrial pressure (HR, 1.34; 95% CI, 0.95-1.90; P=0.0992 and HR, 1.50; 95% CI, 1.20-1.88; P=0.0004), and a history of cancer (HR, 3.02; 95% CI, 1.36-6.69; P=0.0065 and HR, 2.15; 95% CI, 1.18-3.94; P=0.0129) in operated and not-operated patients, respectively. Additional correlates of mortality were bridging therapy with pulmonary arterial hypertension-targeted drugs, postoperative pulmonary hypertension, surgical complications, and additional cardiac procedures in operated patients, and comorbidities such as coronary disease, left heart failure, and chronic obstructive pulmonary disease in not-operated patients. CONCLUSIONS: The long term prognosis of operated patients currently is excellent and better than the outcome of not-operated patients. PMID- 26826182 TI - Functional Analyses of Mutations in Receptor Tyrosine Kinase Genes in Non-Small Cell Lung Cancer: Double-Edged Sword of DDR2. AB - PURPOSE: This study investigated whether mutations of receptor tyrosine kinase (RTK) genes detected using next-generation sequencing (NGS) are suitable therapeutic targets. EXPERIMENTAL DESIGN: Fifty surgically resected non-small cell lung cancer (NSCLC) samples were target resequenced using NGS. We then investigated the functions of the identified RTK gene mutations, including their oncogenic potential, in vitro RESULTS: Mutations in RTK genes were found in 20 samples (EGFR, 15; ERBB4, 1; ALK, 1; DDR2, 2; FGFR1, 1), mutations in MAPK pathway genes were found in nine samples (KRAS, 7; NRAS, 1; BRAF, 2), and mutations in PI3K pathway genes were found in three samples (PIK3CA, 1; PTEN, 3). Among the mutations in RTKs, the functions of four mutations were unclear (ERBB4 D245G; DDR2 H246R and E655K; FGFR1 A263V). These mutations did not exhibit any transformational activities. Neither the phosphorylation nor the protein expressions of RTKs were changed by the DDR2 H246R, ERBB4 D245G, and FGFR1 A263V mutations, although the expression level of the DDR2 protein harboring the E655K mutation was particularly low. Collagen stimulation decreased cellular proliferation through p38 activation in the DDR2 wild-type-overexpressed cell lines, whereas the growth-suppressive effect was weakened in DDR2 E655K overexpressed cell lines. Furthermore, the DDR2 E655K protein strongly bound to ubiquitin ligase E3 (Cbl-b), and the mutant protein expression was increased after treatment with a proteasome inhibitor. CONCLUSIONS: Our experimental findings suggest that RTK mutations are not always suitable as therapeutic targets. The DDR2 E655K mutation can play a role in cancer progression by reducing the growth-inhibitory effect of collagen. Clin Cancer Res; 22(14); 3663 71. (c)2016 AACR. PMID- 26826183 TI - Results of the Fifth Scientific Workshop of the ECCO [II]: Clinical Aspects of Perianal Fistulising Crohn's Disease-the Unmet Needs. AB - BACKGROUND AND AIMS: Perianal fistulas affect up to one-third of Crohn's patients during the course of their disease. Despite the considerable disease burden, current treatment options remain unsatisfactory. The Fifth Scientific Workshop [SWS5] of the European Crohn's and Colitis Organisation [ECCO] focused on the pathophysiology and clinical impact of fistulas in the disease course of patients with Crohn's disease [CD]. METHODS: The ECCO SWS5 Working Group on clinical aspects of perianal fistulising Crohn's disease [pCD] consisted of 13 participants, gastroenterologists, colorectal surgeons, and a histopathologist, with expertise in the field of inflammatory bowel diseases. A systematic review of literature was performed. RESULTS: Four main areas of interest were identified: natural history of pCD, morphological description of fistula tracts, outcome measures [including clinical and patient-reported outcome measures, as well as magnetic resonance imaging] and randomised controlled trials on pCD. CONCLUSIONS: The treatment of perianal fistulising Crohn's disease remains a multidisciplinary challenge. To optimise management, a reliable classification and proper trial endpoints are needed. This could lead to standardised diagnosis, treatment, and follow-up of Crohn's perianal fistulas and the execution of well designed trials that provide clear answers. The prevalence and the natural history of pCD need further evaluation. PMID- 26826185 TI - Inhibition of the PI3K-Akt and mTORC1 signaling pathways promotes the elongation of vascular endothelial cells. AB - Endothelial cell morphology needs to be properly regulated during angiogenesis. Vascular endothelial growth factor (VEGF) induces endothelial cell elongation, which promotes sprouting of pre-existing vessels. However, therapeutic angiogenesis using VEGF has been hampered by side effects such as elevated vascular permeability. Here, we attempted to induce endothelial cell elongation without an overdose of VEGF. By screening a library of chemical inhibitors, we identified phosphatidylinositol 3-kinase (PI3K)-Akt pathway inhibitors and mammalian target of rapamycin complex 1 (mTORC1) inhibitors as potent inducers of endothelial cell elongation. The elongation required VEGF at a low concentration, which was insufficient to elicit the same effect by itself. The elongation also depended on Foxo1, a transcription factor indispensable for angiogenesis. Interestingly, the Foxo1 dependency of the elongation was overridden by inhibition of mTORC1, but not by PI3K-Akt, under stimulation by a high concentration of VEGF. Dual inhibition of mTORC1 and mTORC2 failed to induce cell elongation, revealing mTORC2 as a positive regulator of elongation. Our findings suggest that the PI3K-Akt-Foxo1 and mTORC1-mTORC2 pathways differentially regulate endothelial cell elongation, depending on the microenvironmental levels of VEGF. PMID- 26826184 TI - DAZL and CPEB1 regulate mRNA translation synergistically during oocyte maturation. AB - Meiotic progression requires exquisitely coordinated translation of maternal messenger (m)RNA that has accumulated during oocyte growth. A major regulator of this program is the cytoplasmic polyadenylation element binding protein 1 (CPEB1). However, the temporal pattern of translation at different meiotic stages indicates the function of additional RNA binding proteins (RBPs). Here, we report that deleted in azoospermia-like (DAZL) cooperates with CPEB1 to regulate maternal mRNA translation. Using a strategy that monitors ribosome loading onto endogenous mRNAs and a prototypic translation target, we show that ribosome loading is induced in a DAZL- and CPEB1-dependent manner, as the oocyte reenters meiosis. Depletion of the two RBPs from oocytes and mutagenesis of the 3' untranslated regions (UTRs) demonstrate that both RBPs interact with the Tex19.1 3' UTR and cooperate in translation activation of this mRNA. We observed a synergism between DAZL and cytoplasmic polyadenylation elements (CPEs) in the translation pattern of maternal mRNAs when using a genome-wide analysis. Mechanistically, the number of DAZL proteins loaded onto the mRNA and the characteristics of the CPE might define the degree of cooperation between the two RBPs in activating translation and meiotic progression. PMID- 26826186 TI - SHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration in 1321 N1 glioblastoma cells. AB - Phosphoinositides, particularly phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3] and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], are recognized by SHIP2 (also known as INPPL1) a member of the inositol polyphosphate 5-phosphatase family. SHIP2 dephosphorylates PI(3,4,5)P3 to form PI(3,4)P2; the latter interacts with specific target proteins (e.g. lamellipodin). Although the preferred SHIP2 substrate is PI(3,4,5)P3, PI(4,5)P2 can also be dephosphorylated by this enzyme to phosphatidylinositol 4-phosphate (PI4P). Through depletion of SHIP2 in the glioblastoma cell line 1321 N1, we show that SHIP2 inhibits cell migration. In different glioblastoma cell lines and primary cultures, SHIP2 staining at the plasma membrane partly overlaps with PI(4,5)P2 immunoreactivity. PI(4,5)P2 was upregulated in SHIP2-deficient N1 cells as compared to control cells; in contrast, PI4P was very much decreased in SHIP2-deficient cells. Therefore, SHIP2 controls both PI(3,4,5)P3 and PI(4,5)P2 levels in intact cells. In 1321 N1 cells, the PI(4,5)P2-binding protein myosin-1c was identified as a new interactor of SHIP2. Regulation of PI(4,5)P2 and PI4P content by SHIP2 controls 1321 N1 cell migration through the organization of focal adhesions. Thus, our results reveal a new role of SHIP2 in the control of PI(4,5)P2, PI4P and cell migration in PTEN-deficient glioblastoma 1321 N1 cells. PMID- 26826187 TI - Soluble LILRA3 promotes neurite outgrowth and synapses formation through a high affinity interaction with Nogo 66. AB - Inhibitory proteins, particularly Nogo 66, a highly conserved 66-amino-acid loop of Nogo A (an isoform of RTN4), play key roles in limiting the intrinsic capacity of the central nervous system (CNS) to regenerate after injury. Ligation of surface Nogo receptors (NgRs) and/or leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse orthologue the paired immunoglobulin-like receptor B (PIRB) by Nogo 66 transduces inhibitory signals that potently inhibit neurite outgrowth. Here, we show that soluble leukocyte immunoglobulin-like receptor A3 (LILRA3) is a high-affinity receptor for Nogo 66, suggesting that LILRA3 might be a competitive antagonist to these cell surface inhibitory receptors. Consistent with this, LILRA3 significantly reversed Nogo-66-mediated inhibition of neurite outgrowth and promoted synapse formation in primary cortical neurons through regulation of the ERK/MEK pathway. LILRA3 represents a new antagonist to Nogo-66 mediated inhibition of neurite outgrowth in the CNS, a function distinct from its immune-regulatory role in leukocytes. This report is also the first to demonstrate that a member of LILR family normally not expressed in rodents exerts functions on mouse neurons through the highly homologous Nogo 66 ligand. PMID- 26826188 TI - Activator of G-protein signaling 8 is involved in VEGF-mediated signal processing during angiogenesis. AB - Activator of G-protein signaling 8 (AGS8, also known as FNDC1) is a receptor independent accessory protein for the Gbetagamma subunit, which was isolated from rat heart subjected to repetitive transient ischemia with the substantial development of collaterals. Here, we report the role of AGS8 in vessel formation by endothelial cells. Knockdown of AGS8 by small interfering RNA (siRNA) inhibited vascular endothelial growth factor (VEGF)-induced tube formation, as well as VEGF-stimulated cell growth and migration. VEGF stimulated the phosphorylation of the VEGF receptor-2 (VEGFR-2, also known as KDR), ERK1/2 and p38 MAPK; however, knockdown of AGS8 inhibited these signaling events. Signal alterations by AGS8 siRNA were associated with a decrease of cell surface VEGFR-2 and an increase of VEGFR-2 in the cytosol. Endocytosis blockers did not influence the decrease of VEGFR-2 by AGS8 siRNA, suggesting the involvement of AGS8 in VEGFR-2 trafficking to the plasma membrane. VEGFR-2 formed a complex with AGS8 in cells, and a peptide designed to disrupt AGS8-Gbetagamma interaction inhibited VEGF-induced tube formation. These data suggest a potential role for AGS8 Gbetagamma in VEGF signal processing. AGS8 might play a key role in tissue adaptation by regulating angiogenic events. PMID- 26826189 TI - Proteasome storage granules are transiently associated with the insoluble protein deposit in Saccharomyces cerevisiae. AB - Proteasome storage granules (PSGs) are created in yeast as part of an extensive and programmed reorganization of proteins into reversible assemblies upon carbon source depletion. Here, we demonstrate that cells distinguish dysfunctional proteasomes from PSGs on the cytosolic insoluble protein deposit (IPOD). Furthermore, we provide evidence that this is a general mechanism for the reorganization of additional proteins into reversible assemblies. Our study expands the roles of the IPOD, which might serve not only as the specific depository for amyloidogenic and misfolded proteins, but also as a potential hub from which proteins are directed to distinct cellular compartments. These findings therefore provide a framework for understanding how cells discriminate between intact and abnormal proteins under stress conditions to ensure that only structurally 'correct' proteins are deployed. PMID- 26826190 TI - Systems Pharmacology Analysis of the Amyloid Cascade after beta-Secretase Inhibition Enables the Identification of an Abeta42 Oligomer Pool. AB - The deposition of amyloid-beta (Abeta) oligomers in brain parenchyma has been implicated in the pathophysiology of Alzheimer's disease. Here we present a systems pharmacology model describing the changes in the amyloid precursor protein (APP) pathway after administration of three different doses (10, 30, and 125 mg/kg) of the beta-secretase 1 (BACE1) inhibitor MBi-5 in cisterna magna ported rhesus monkeys. The time course of the MBi-5 concentration in plasma and cerebrospinal fluid (CSF) was analyzed in conjunction with the effect on the concentrations of the APP metabolites Abeta42, Abeta40, soluble beta-amyloid precursor protein (sAPP) alpha, and sAPPbeta in CSF. The systems pharmacology model contained expressions to describe the production, elimination, and brain-to CSF transport for the APP metabolites. Upon administration of MBi-5, a dose dependent increase of the metabolite sAPPalpha and dose-dependent decreases of sAPPbeta and Abeta were observed. Maximal inhibition of BACE1 was close to 100% and the IC50 value was 0.0256 MUM (95% confidence interval, 0.0137-0.0375). A differential effect of BACE1 inhibition on Abeta40 and Abeta42 was observed, with the Abeta40 response being larger than the Abeta42 response. This enabled the identification of an Abeta42 oligomer pool in the systems pharmacology model. These findings indicate that decreases in monomeric Abeta responses resulting from BACE1 inhibition are partially compensated by dissociation of Abeta oligomers and suggest that BACE1 inhibition may also reduce the putatively neurotoxic oligomer pool. PMID- 26826191 TI - Comparisons of Delta9-Tetrahydrocannabinol and Anandamide on a Battery of Cognition-Related Behavior in Nonhuman Primates. AB - The primary psychoactive ingredient of marijuana, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), has medicinal value but also produces unwanted deleterious effects on cognitive function, promoting the search for improved cannabinergic therapeutics. The present studies used a battery of touchscreen procedures in squirrel monkeys to compare the effects of different types of cannabinergic drugs on several measures of performance including learning (repeated acquisition), cognitive flexibility (discrimination reversal), short-term memory (delayed matching-to-sample), attention (psychomotor vigilance), and motivation (progressive ratio). Drugs studied included the cannabinoid agonist Delta(9)-THC, fatty acid amide hydrolase (FAAH) inhibitor cyclohexylcarbamic acid 3 carbamoylbiphenyl-3-yl ester (URB597), and endocannabinoid anandamide and its stable synthetic analog methanandamide [(R)-(+)-arachidonyl-1'-hydroxy-2' propylamide]. The effects of Delta(9)-THC and anandamide after treatment with the cannabinoid receptor type 1 inverse agonist/antagonist rimonabant [5-(4 chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1Hpyrazole-3 carboxamide] and the FAAH inhibitor URB597, respectively, also were examined. The results showed the following: 1) Delta(9)-THC produced dose-related impairments of discrimination-based cognitive behavior with potency that varied across tasks (discriminative capability < learning < flexibility < short-term memory); 2) anandamide alone and URB597 alone were without effect on all endpoints; 3) anandamide following URB597 pretreatment and methanandamide had negligible effects on discriminative capability, learning, and reversal, but following large doses affected delayed matching-to-sample performance in some subjects; 4) all drugs, except anandamide and URB597, disrupted attention; and 5) progressive ratio breakpoints were generally unaffected by all drugs tested, suggesting little to no effect on motivation. Taken together, these data indicate that metabolically stable forms of anandamide may have lesser adverse effects on cognitive functions than Delta(9)-THC, possibly offering a therapeutic advantage in clinical settings. PMID- 26826192 TI - Combat casualties from two current conflicts with the Seventh French Forward Surgical Team in Mali and Central African Republic in 2014. AB - OBJECTIVES: The Seventh Airborne Forward Surgical Team (FST) has been deployed in Gao, Mali, and in Bangui, Central African Republic (CAR), for two 3-month periods in 2014. The initial role of the FST was to provide emergent care to French and coalition soldiers but it was expanded to include humanitarian assistance. The aim of the present study was to describe and compare injuries and surgical activity of the Seventh Airborne FST during these two conflicts. METHODS: All surgical patients treated by the FST between January and December 2014 have been included. Patient demographics, mechanisms of injury, surgical management including triage categories and types of surgery performed and evacuation modalities were recorded. RESULTS: During the 6-month deployment period in 2014, the FST performed 129 operations on 134 patients, 61 of which were trauma patients (45 battle injuries (BI)). The remaining 73 patients were treated as part of the humanitarian mission. Thirty of the BI were managed during the Malian conflict and 15 in CAR; 29 patients (64%) were military. The median Injury Severity Score (range) was 20 (10-34) in Mali and 8 (5-21) in CAR with median (range) evacuation time of 390 min (240-947) in Mali and 120 min (60-120) in CAR (p<0.0001). The most frequent mechanisms of injury were gunshot wounds in Mali (15/30) and road traffic accident in CAR (7/15). Extremity injuries were most common (58%) with head, face and neck injuries and thoracic injuries in 15% of cases each and 12% had suffered abdominopelvic injuries. Ten patients were categorised as T1 and underwent urgent surgery, five had damage control surgery and four received transfusion. The average length of stay was 2 days (1-2), with most patients being transferred to another hospital. CONCLUSIONS: Casualties from Mali and CAR presented with a wide variety of injury patterns, and there were some instances where damage control surgery and whole blood transfusion were necessary. Surgical equipment scales must allow treatment of a large variety of injuries including all body regions and extreme emergency procedures. These two conflicts differ in terms of scope, one being an urban guerrilla and the other an open conflict in a large desertic area. Long distances in the Malian desert increase significantly the evacuation time. It has to be taken into account in the FST location when coalition forces are deployed in such places. PMID- 26826193 TI - Parasite Strain, Host Immunity, and Circulating Blood Cells with Dead Parasites: Why Predicting Malaria Parasite Clearance Is Not a Simple Task. PMID- 26826194 TI - Reply to "Parasite Strain, Host Immunity, and Circulating Blood Cells with Dead Parasites: Why Predicting Malaria Parasite Clearance Is Not a Simple Task". PMID- 26826195 TI - Erratum for Yang et al., Resistome Analysis of Enterobacter cloacae CY01, an Extensively Drug-Resistant Strain Producing VIM-1 Metallo-beta-Lactamase from China. PMID- 26826197 TI - Application of cell sorting for enhancing the performance of the cytokinesis block micronucleus assay. AB - Among the numerous methods available to assess genotoxicity, the cytokinesis block micronucleus (CBMN) assay is very popular due its relative simplicity and power to detect both clastogenic and aneugenic compounds. A problem with the CBMN assay is that all DNA damaging agents also inhibit the ability of cells to progress through mitosis, leading to a low number of binucleated cells (BNCs). One method to resolve this issue is to ensure a sufficient proportion of BNCs in the samples. In the current study, the applicability of a cell sorting system capable of isolating cell fractions containing abundant BNCs was investigated. Furthermore, to investigate the relationship between the cell division delay due to radiation exposure and the generation of BNCs and micronuclei (MN), we assessed a series of lag times between radiation exposure and addition of cytochalasin-B (Cyt-B). Cells from the human chronic myelogenous leukemia cell line K562 were exposed to X-rays (2 Gy and 4 Gy), and Cyt-B was subsequently added at 0, 6 and 12 h following irradiation. After treatment with Cyt-B for 24 h, the percentage of BNCs, the MN frequency and the cell cycle distribution were analyzed. In addition, cells displaying the DNA contents corresponding to BNCs were isolated and analyzed. The results indicate that applying the cell sorter to the CBMN assay increased the percentage of BNCs compared with the standard method. Thus, this technique is a promising way of enhancing the capacity of the CBMN assay. PMID- 26826198 TI - Prognostic impact of average iodine density assessed by dual-energy spectral imaging for predicting lung tumor recurrence after stereotactic body radiotherapy. AB - The purpose of this study was to investigate the prognostic significance of average iodine density as assessed by dual-energy computed tomography (DE-CT) for lung tumors treated with stereotactic body radiotherapy (SBRT). From March 2011 to August 2014, 93 medically inoperable patients with 74 primary lung cancers and 19 lung metastases underwent DE-CT prior to SBRT of a total dose of 45-60 Gy in 5 10 fractions. Of these 93 patients, nine patients had two lung tumors. Thus, 102 lung tumors were included in this study. DE-CT was performed for pretreatment evaluation. Regions of interest were set for the entire tumor, and average iodine density was obtained using a dedicated imaging software and evaluated with regard to local control. The median follow-up period was 23.4 months (range, 1.5-54.5 months). The median value of the average iodine density was 1.86 mg/cm(3) (range, 0.40-9.27 mg/cm(3)). Two-year local control rates for the high and low average iodine density groups divided by the median value of the average iodine density were 96.9% and 75.7% (P = 0.006), respectively. Tumors with lower average iodine density showed a worse prognosis, possibly reflecting a hypoxic cell population in the tumor. The average iodine density exhibited a significant impact on local control. Our preliminary results indicate that iodine density evaluated using dual-energy spectral CT may be a useful, noninvasive and quantitative assessment of radio-resistance caused by presumably hypoxic cell populations in tumors. PMID- 26826199 TI - Hepcidin-2 in mouse urine as a candidate radiation-responsive molecule. AB - We used high-performance liquid chromatography to separate urine obtained from whole-body gamma-irradiated mice (4 Gy) before analyzing each fraction with matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry to identify radiation-responsive molecules. We identified two candidates: hepcidin antimicrobial peptide 2 (hepcidin-2) and peptide fragments of kidney androgen regulated protein (KAP). We observed that peak increases of hepcidin-2 in urine were delayed in a dose-dependent manner (1 Gy and above); however, the amount of KAP peptide fragments showed no correlation with radiation dose. In addition, an increase in hepcidin-2 after exposure to relatively low radiation doses (0.25 and 0.5 Gy, respectively) was biphasic (at 8-48 h and 120-168 h, respectively, after irradiation). The increase in hepcidin-2 paralleled an increase in hepcidin-2 gene (Hamp2) mRNA levels in the liver. These results suggest that radiation exposure directly or indirectly induces urinary excretion of hepcidin-2 at least in part by the upregulation of Hamp2 mRNA in the liver. PMID- 26826200 TI - Percutaneous fiducial marker placement prior to stereotactic body radiotherapy for malignant liver tumors: an initial experience. AB - The aim of this study was to describe our initial experience with a gold flexible linear fiducial marker and to evaluate the safety and technical and clinical efficacy of stereotactic body radiotherapy using this marker for malignant liver tumors. Between July 2012 and February 2015, 18 patients underwent percutaneous fiducial marker placement before stereotactic body radiotherapy for malignant liver tumors. We evaluated the technical and clinical success rates of the procedure and the associated complications. Technical success was defined as successful placement of the fiducial marker at the target site, and clinical success was defined as the completion of stereotactic body radiotherapy without the marker dropping out of position. All 18 fiducial markers were placed successfully, so the technical success rate was 100% (18/18). All 18 patients were able to undergo stereotactic body radiotherapy without marker migration. Thus, the clinical success rate was 100% (18/18). Slight pneumothorax occurred as a minor complication in one case. No major complications such as coil migration or bleeding were observed. The examined percutaneous fiducial marker was safely placed in the liver and appeared to be useful for stereotactic body radiotherapy for malignant liver tumors. PMID- 26826201 TI - Oncogenic PI3K mutations are as common as AKT1 and SMO mutations in meningioma. AB - BACKGROUND: Meningiomas are the most common primary intracranial tumor in adults. Identification of SMO and AKT1 mutations in meningiomas has raised the possibility of targeted therapies for some patients. The frequency of such mutations in clinical cohorts and the presence of other actionable mutations in meningiomas are important to define. METHODS: We used high-resolution array comparative genomic hybridization to prospectively characterize copy-number changes in 150 meningiomas and then characterized these samples for mutations in AKT1, KLF4, NF2, PIK3CA, SMO, and TRAF7. RESULTS: Similar to prior reports, we identified AKT1 and SMO mutations in a subset of non-NF2-mutant meningiomas (ie, ~9% and ~6%, respectively). Notably, we detected oncogenic mutations in PIK3CA in ~7% of non-NF2-mutant meningiomas. AKT1, SMO, and PIK3CA mutations were mutually exclusive. AKT1, KLF4, and PIK3CA mutations often co-occurred with mutations in TRAF7. PIK3CA-mutant meningiomas showed limited chromosomal instability and were enriched in the skull base. CONCLUSION: This work identifies PI3K signaling as an important target for precision medicine trials in meningioma patients. PMID- 26826202 TI - Core pathway mutations induce de-differentiation of murine astrocytes into glioblastoma stem cells that are sensitive to radiation but resistant to temozolomide. AB - BACKGROUND: Glioma stem cells (GSCs) from human glioblastomas (GBMs) are resistant to radiation and chemotherapy and may drive recurrence. Treatment efficacy may depend on GSCs, expression of DNA repair enzymes such as methylguanine methyltransferase (MGMT), or transcriptome subtype. METHODS: To model genetic alterations in human GBM core signaling pathways, we induced Rb knockout, Kras activation, and Pten deletion mutations in cortical murine astrocytes. Neurosphere culture, differentiation, and orthotopic transplantation assays were used to assess whether these mutations induced de-differentiation into GSCs. Genome-wide chromatin landscape alterations and expression profiles were examined by formaldehyde-assisted isolation of regulatory elements (FAIRE) seq and RNA-seq. Radiation and temozolomide efficacy were examined in vitro and in an allograft model in vivo. Effects of radiation on transcriptome subtype were examined by microarray expression profiling. RESULTS: Cultured triple mutant astrocytes gained unlimited self-renewal and multilineage differentiation capacity. These cells harbored significantly altered chromatin landscapes that were associated with downregulation of astrocyte- and upregulation of stem cell associated genes, particularly the Hoxa locus of embryonic transcription factors. Triple-mutant astrocytes formed serially transplantable glioblastoma allografts that were sensitive to radiation but expressed MGMT and were resistant to temozolomide. Radiation induced a shift in transcriptome subtype of GBM allografts from proneural to mesenchymal. CONCLUSION: A defined set of core signaling pathway mutations induces de-differentiation of cortical murine astrocytes into GSCs with altered chromatin landscapes and transcriptomes. This non-germline genetically engineered mouse model mimics human proneural GBM on histopathological, molecular, and treatment response levels. It may be useful for dissecting the mechanisms of treatment resistance and developing more effective therapies. PMID- 26826203 TI - Methylation profiling of choroid plexus tumors reveals 3 clinically distinct subgroups. AB - BACKGROUND: Choroid plexus tumors are intraventricular neoplasms derived from the choroid plexus epithelium. A better knowledge of molecular factors involved in choroid plexus tumor biology may aid in identifying patients at risk for recurrence. METHODS: Methylation profiles were examined in 29 choroid plexus papillomas (CPPs, WHO grade I), 32 atypical choroid plexus papillomas (aCPPs, WHO grade II), and 31 choroid plexus carcinomas (CPCs, WHO grade III) by Illumina Infinium HumanMethylation450 Bead Chip Array. RESULTS: Unsupervised hierarchical clustering identified 3 subgroups: methylation cluster 1 (pediatric CPP and aCPP of mainly supratentorial location), methylation cluster 2 (adult CPP and aCPP of mainly infratentorial location), and methylation cluster 3 (pediatric CPP, aCPP, and CPC of supratentorial location). In methylation cluster 3, progression-free survival (PFS) accounted for a mean of 72 months (CI, 55-89 mo), whereas only 1 of 42 tumors of methylation clusters 1 and 2 progressed (P< .001). On stratification of outcome data according to WHO grade, all CPCs clustered within cluster 3 and were associated with shorter overall survival (mean, 105 mo [CI, 81 128 mo]) and PFS (mean, 55 mo [CI, 36-73 mo]). The aCPP of methylation cluster 3 also progressed frequently (mean, 69 mo [CI, 44-93 mo]), whereas no tumor progression was observed in aCPP of methylation clusters 1 and 2 (P< .05). Only 1 of 29 CPPs recurred. CONCLUSIONS: Methylation profiling of choroid plexus tumors reveals 3 distinct subgroups (ie, pediatric low-risk choroid plexus tumors [cluster 1], adult low-risk choroid plexus tumors [cluster 2], and pediatric high risk choroid plexus tumors [cluster 3]) and may provide useful prognostic information in addition to histopathology. PMID- 26826204 TI - Increased CSF neurogranin concentration is specific to Alzheimer disease. AB - OBJECTIVE: To assess the specificity of the dendritic protein neurogranin (Ng) in CSF from patients with a broad range of neurodegenerative diseases including a variety of dementias, tauopathies, and synucleinopathies. METHOD: An optimized immunoassay was used to analyze CSF Ng in a retrospective cohort of 331 participants with different neurodegenerative diseases, including healthy controls (n = 19), biomarker-proven Alzheimer disease (AD) (n = 100), genetic AD (n = 2), behavioral variant frontotemporal dementia (n = 20), speech variant frontotemporal dementia (n = 21), Lewy body dementia (n = 13), Parkinson disease (n = 31), progressive supranuclear palsy (n = 46), multiple system atrophy (n = 29), as well as a heterogeneous group with non-neurodegenerative cognitive impairment (n = 50). CSF Ng concentrations and correlations of CSF Ng with total tau, phosphorylated tau, and beta-amyloid 42 concentrations, Mini-Mental State Examination score, and disease duration in the different groups were investigated. RESULTS: Median CSF Ng concentration was higher in patients with AD compared to both controls (p < 0.001) and all other disease groups (all p < 0.001) except speech variant frontotemporal dementia. There were no significant differences in CSF Ng concentrations between any other neurodegenerative groups and controls. In addition, we found strong correlations between Ng and total tau (p < 0.001) and phosphorylated tau (p < 0.001). CONCLUSIONS: These results confirm an increase in CSF Ng concentration in patients with AD as previously reported and show that this is specific to AD and not seen in a range of other neurodegenerative diseases. PMID- 26826206 TI - Acute retinal necrosis in multiple sclerosis: A neuroimmunologic challenge! PMID- 26826207 TI - A new type of cervical vertigo: Head motion-induced spells in acute neck pain. PMID- 26826208 TI - In TNF-stimulated cells, RIPK1 promotes cell survival by stabilizing TRAF2 and cIAP1, which limits induction of non-canonical NF-kappaB and activation of caspase-8. PMID- 26826210 TI - An international survey on the current use of electroacupuncture. AB - BACKGROUND: Despite many research publications, it is unclear how widely electroacupuncture (EA) and related modalities are used in everyday practice. It is also uncertain who uses them, for what conditions, and with what results. We aimed to survey practitioners about their use of and training in EA. We also sought to determine how much the open-access English-language database at http://www.electroacupunctureknowledge.com (EAK) is used, or might be used in the future, if updated. METHODS: A survey was developed using several rounds of consultation with a focus group and others. Professional acupuncture membership organisations were contacted to assess their willingness to notify their members. The survey was tested before its launch. RESULTS: Thirty-four professional organisations agreed to participate, together with two research bodies and six UK training institutes. Potentially, around 50 000 professionals practising acupuncture knew about the survey, to which there were 768 responses. Data were analysed for respondent demographics. Around 70% used EA, but <25% used related electrotherapy modalities. Men were more likely than women to use more than one modality. Only around 7% of respondents used non-traditional acupuncture modalities without prior training. However, awareness and usage of the EAK database was low, although around 80% of respondents stated they might use the database in the future, primarily to improve clinical practice. CONCLUSIONS: To the best of our knowledge, this is the largest survey on EA and related modalities ever conducted. As such, its results are likely to be of interest to acupuncture and other practitioners (whether or not they use EA), patients, policymakers, and funding agencies. PMID- 26826211 TI - Stunting risk of orphans by caregiver and living arrangement in low-income and middle-income countries. AB - BACKGROUND: An estimated 151 million children worldwide have lost one or both parents (UNICEF). Although a considerable literature has documented the impact of parental loss on children's emotional development, to date there are mixed findings regarding the potential effect of orphanhood on children's physical growth. The aim of the study is to examine the association between orphanhood (maternal, paternal or both) on childhood stunting status, accounting for living arrangement. METHODS: We combine nationally representative data from 84 Demographic Health Surveys for 49 low-income and middle-income countries (LMICs). Data from 222 690 children aged 0-23 months were included in the analytical sample. We show pooled estimates from multiple analysis models, as well as models examining the role of the surviving parent's residence and household structure. RESULTS: In fully adjusted models, maternal orphans were found to have an increased risk of stunting (RR 1.3, 95% CI 1.2 to 1.4) compared to children with two living parents. The stratified models demonstrated that the greatest risk was observed for maternal orphans whose surviving fathers did not live with the child (RR 1.4, 95% CI 1.3 to 1.6). CONCLUSIONS: Early orphanhood constitutes a major risk for children's physical development in LMICs. However, the results suggest that the adverse effects of a parental loss can be mitigated if appropriate support is provided, indicating the potential benefits of the surviving parents staying with their children. The benefits of targeted social policies aimed at single fathers and grandparents supporting orphans may be significant. PMID- 26826209 TI - The Language of Cigar Use: Focus Group Findings on Cigar Product Terminology. AB - INTRODUCTION: The consumption of cigar products has increased since 2000. The multiple product types within this category, combined with the varied language with which consumers refer to them, present challenges for accurately assessing the prevalence of cigar product use. Surveillance is also complicated by the fact that these products can be used to smoke marijuana, as "blunts"-cigars in which the tobacco is removed and replaced with marijuana. Few studies exist regarding the language and terminology used to describe these products. METHODS: Sixteen focus groups were conducted in five cities in the United States between March and May of 2014. Participants (N = 123) included adults who had used cigars, cigarillos, or little cigars in the past 30 days. A semi-structured moderator guide was used to gather data on the terms used to identify cigar product subtypes and the language used to describe the products and their use. RESULTS: Participants used a variety of terms for each product subtype. Brand names were often used, as well as slang terms, including terms describing cigars modified for marijuana use. Some subtypes were less likely than others to be considered "cigars." Participants had mixed opinions about whether users of cigar products are "smokers." CONCLUSIONS: Users of cigar products may classify or label products differently from researchers and policy makers, and many refer to their product by brand name or a slang term. These findings have implications for future research, instrument design, and public health messaging about cigar products. IMPLICATIONS: This study adds to the body of evidence highlighting the challenges for measurement and surveillance of non-cigarette tobacco products, including cigars. Findings illustrate the myriad terms used by consumers to describe their use of cigar product subtypes, as well as the complexity of distinguishing between use of cigar products as intended, versus as a vehicle for smoking marijuana. Future research aimed to enhance specificity of cigar use measures will enable policy-makers and public health practitioners to more fully characterize prevalence and patterns of use by cigar subtype. PMID- 26826205 TI - Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study. AB - OBJECTIVE: To compare natalizumab and fingolimod on both clinical and MRI outcomes in patients with relapsing-remitting multiple sclerosis (RRMS) from 27 multiple sclerosis centers participating in the French follow-up cohort Observatoire of Multiple Sclerosis. METHODS: Patients with RRMS included in the study were aged from 18 to 65 years with an Expanded Disability Status Scale score of 0-5.5 and an available brain MRI performed within the year before treatment initiation. The data were collected for 326 patients treated with natalizumab and 303 with fingolimod. The statistical analysis was performed using 2 different methods: logistic regression and propensity scores (inverse probability treatment weighting). RESULTS: The confounder-adjusted proportion of patients with at least one relapse within the first and second year of treatment was lower in natalizumab-treated patients compared to the fingolimod group (21.1% vs 30.4% at first year, p = 0.0092; and 30.9% vs 41.7% at second year, p = 0.0059) and supported the trend observed in nonadjusted analysis (21.2% vs 27.1% at 1 year, p = 0.0775). Such statistically significant associations were also observed for gadolinium (Gd)-enhancing lesions and new T2 lesions at both 1 year (Gd-enhancing lesions: 9.3% vs 29.8%, p < 0.0001; new T2 lesions: 10.6% vs 29.6%, p < 0.0001) and 2 years (Gd-enhancing lesions: 9.1% vs 22.1%, p = 0.0025; new T2 lesions: 16.9% vs 34.1%, p = 0.0010) post treatment initiation. CONCLUSION: Taken together, these results suggest the superiority of natalizumab over fingolimod to prevent relapses and new T2 and Gd-enhancing lesions at 1 and 2 years. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with RRMS, natalizumab decreases the proportion of patients with at least one relapse within the first year of treatment compared to fingolimod. PMID- 26826212 TI - The influence of refugee status and secondary migration on preterm birth. AB - BACKGROUND: It is unknown whether the risk of preterm birth (PTB) is elevated for forced (refugee) international migrants and whether prolonged displacement amplifies risk. While voluntary migrants who arrive from a country other than their country of birth (ie, secondary migrants) have favourable birth outcomes compared with those who migrated directly from their country of birth (ie, primary migrants), secondary migration may be detrimental for refugees who experience distinct challenges in transition countries. Our objectives were (1) to determine whether refugee status was associated with PTB and (2) whether the relation between refugee status and PTB differed between secondary and primary migrants. METHODS: We conducted a retrospective population-based cohort study. Ontario immigration (2002-2010) and hospitalisation data (2002-2010) were linked to estimate adjusted cumulative odds ratios (ACOR) of PTB (22-31, 32-36, 37-41 weeks of gestation), with 95% CIs (95% CI) comparing refugees with non-refugees. We further included a product term between refugee status and secondary migration. RESULTS: Overall, refugees (N=12 913) had 17% greater cumulative odds of short gestation (ACOR=1.17, 95% CI 1.07 to 1.28) compared with non-refugees (N=110 640). Secondary migration modified the association between refugee status and PTB (p=0.007). Secondary refugees had 58% greater cumulative odds of short gestation (ACOR=1.58, 95% CI 1.25 to 2.00) than secondary non-refugees, while primary refugees had 12% greater cumulative odds of short gestation (ACOR=1.12, 95% CI 1.02 to 1.23) than primary non-refugee immigrants. CONCLUSIONS: Refugee status, jointly with secondary migration, influences PTB among migrants. PMID- 26826213 TI - Improving Global Child Health: Why All Pediatricians Must "Be the Change". PMID- 26826214 TI - The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities. AB - BACKGROUND: Obesity and diabetes are highly prevalent among pregnant women in the United States. No study has examined the independent and combined effects of maternal prepregnancy obesity and maternal diabetes on the risk of autism spectrum disorder (ASD) in parallel with other developmental disorders (DDs). METHODS: This study is based on 2734 children (including 102 ASD cases), a subset of the Boston Birth Cohort who completed at least 1 postnatal study visit at Boston Medical Center between 1998 and 2014. Child ASD and other DDs were based on physician diagnoses as documented in electronic medical records. Risks of ASD and other DDs were compared among 6 groups defined by maternal prepregnancy obesity and diabetes status by using Cox proportional hazard regression controlling for potential confounders. RESULTS: When examined individually, maternal prepregnancy obesity and pregestational diabetes (PGDM) were each associated with risk of ASD. When examined in combination, only mothers with obesity and PGDM (hazard ratio 3.91, 95% confidence interval 1.76-8.68) and those with obesity and gestational diabetes (hazard ratio 3.04, 95% confidence interval 1.21-7.63) had a significantly increased risk of offspring ASD. Intellectual disabilities (IDs), but not other DDs, showed a similar pattern of increased risk associated with combined obesity and PGDM. This pattern of risk was mostly accounted for by cases with co-occurring ASD and ID. CONCLUSIONS: Maternal prepregnancy obesity and maternal diabetes in combination were associated with increased risk for ASD and ID. ASD with ID may be etiologically distinct from ASD without ID. PMID- 26826215 TI - Dating Violence and Injury Among Youth Exposed to Violence. AB - OBJECTIVES: To assess gender differences in the proportion of adolescents reporting teen dating violence (TDV) and the frequency of TDV at multiple age points across adolescence in a high-risk sample of youth with previous exposure to violence. METHODS: A cross-sectional, high-risk sample of boys and girls (n = 1149) ages 11 to 17 years completed surveys assessing TDV and self-defense. Indices of TDV included perpetration and victimization scales of controlling behaviors, psychological TDV, physical TDV, sexual TDV, fear/intimidation, and injury. RESULTS: More girls reported perpetrating psychological and physical TDV, whereas twice as many boys reported sexual TDV perpetration. More girls reported fear/intimidation victimization than boys. When comparing the frequency of TDV across adolescence, boys reported more sexual TDV victimization at younger ages, and girls demonstrated a trend toward more victimization at older ages. Likewise, younger boys reported more fear/intimidation and injury perpetration and injury victimization than younger girls. However, by age 17, girls reported more injury perpetration than boys, and reports of injury victimization and use of self defense did not differ. Notably, despite potential parity in injury, girls consistently reported more fear/intimidation victimization associated with TDV. CONCLUSIONS: Contrary to data suggesting that girls experience far more sexual TDV and injury, these data suggest that at specific times during adolescence, boys among high-risk populations may be equally at risk for victimization. However, the psychological consequences (fear) are greater for girls. These findings suggest a need to tailor strategies to prevent TDV based on both age- and gender-specific characteristics in high-risk populations. PMID- 26826216 TI - Cytokinin delays dark-induced senescence in rice by maintaining the chlorophyll cycle and photosynthetic complexes. AB - The phytohormone cytokinin (CK) is known to delay senescence in plants. We studied the effect of a CK analog, 6-benzyl adenine (BA), on rice leaves to understand the possible mechanism by which CK delays senescence in a drought- and heat-tolerant rice cultivar Nagina22 (N22) using dark-induced senescence (DIS) as a surrogate for natural senescence of leaves. Leaves of N22-H-dgl162, a stay green mutant of N22, and BA-treated N22 showed retention of chlorophyll (Chl) pigments, maintenance of the Chl a/b ratio, and delay in reduction of both photochemical efficiency and rate of oxygen evolution during DIS. HPLC analysis showed accumulation of 7-hydroxymethyl chlorophyll (HmChl) during DIS, and the kinetics of its accumulation correlated with progression of senescence. Transcriptome analysis revealed that several plastid-localized genes, specifically those associated with photosystem II (PSII), showed higher transcript levels in BA-treated N22 and the stay-green mutant leaves compared with naturally senescing N22 leaves. Real-time PCR analyses showed that genes coding for enzymes associated with Chl a/b interconversion and proteins associated with light-harvesting complexes maintained higher transcript levels up to 72h of DIS following BA treatment. The pigment-protein complexes analyzed by green gel remained intact in both N22-H-dgl162 and BA-treated N22 leaves even after 96h of DIS. Thus, CK delays senescence by accumulation of HmChl and up regulating genes in the Chl cycle, thereby maintaining the Chl a/b ratio. Also, CK treatment retains higher transcript levels of PSII-related genes, resulting in the stability of photosynthetic pigment complexes and functional stay-greenness in rice. PMID- 26826217 TI - A new three-locus model for rootstock-induced dwarfing in apple revealed by genetic mapping of root bark percentage. AB - Rootstock-induced dwarfing of apple scions revolutionized global apple production during the twentieth century, leading to the development of modern intensive orchards. A high root bark percentage (the percentage of the whole root area constituted by root cortex) has previously been associated with rootstock-induced dwarfing in apple. In this study, the root bark percentage was measured in a full sib family of ungrafted apple rootstocks and found to be under the control of three loci. Two quantitative trait loci (QTLs) for root bark percentage were found to co-localize to the same genomic regions on chromosome 5 and chromosome 11 previously identified as controlling dwarfing, Dw1 and Dw2, respectively. A third QTL was identified on chromosome 13 in a region that has not been previously associated with dwarfing. The development of closely linked sequence tagged site markers improved the resolution of allelic classes, thereby allowing the detection of dominance and epistatic interactions between loci, with high root bark percentage only occurring in specific allelic combinations. In addition, we report a significant negative correlation between root bark percentage and stem diameter (an indicator of tree vigour), measured on a clonally propagated grafted subset of the mapping population. The demonstrated link between root bark percentage and rootstock-induced dwarfing of the scion leads us to propose a three-locus model that is able to explain levels of dwarfing from the dwarf 'M.27' to the semi-invigorating rootstock 'M.116'. Moreover, we suggest that the QTL on chromosome 13 (Rb3) might be analogous to a third dwarfing QTL, Dw3, which has not previously been identified. PMID- 26826219 TI - A portable fluorescence spectroscopy imaging system for automated root phenotyping in soil cores in the field. AB - Root architecture traits are a target for pre-breeders. Incorporation of root architecture traits into new cultivars requires phenotyping. It is attractive to rapidly and directly phenotype root architecture in the field, avoiding laboratory studies that may not translate to the field. A combination of soil coring with a hydraulic push press and manual core-break counting can directly phenotype root architecture traits of depth and distribution in the field through to grain development, but large teams of people are required and labour costs are high with this method. We developed a portable fluorescence imaging system (BlueBox) to automate root counting in soil cores with image analysis software directly in the field. The lighting system was optimized to produce high-contrast images of roots emerging from soil cores. The correlation of the measurements with the root length density of the soil cores exceeded the correlation achieved by human operator measurements (R (2)=0.68 versus 0.57, respectively). A BlueBox equipped team processed 4.3 cores/hour/person, compared with 3.7 cores/hour/person for the manual method. The portable, automated in-field root architecture phenotyping system was 16% more labour efficient, 19% more accurate, and 12% cheaper than manual conventional coring, and presents an opportunity to directly phenotype root architecture in the field as part of pre-breeding programs. The platform has wide possibilities to capture more information about root health and other root traits in the field. PMID- 26826218 TI - Loose Plant Architecture1 (LPA1) determines lamina joint bending by suppressing auxin signalling that interacts with C-22-hydroxylated and 6-deoxo brassinosteroids in rice. AB - Lamina inclination is a key agronomical character that determines plant architecture and is sensitive to auxin and brassinosteroids (BRs). Loose Plant Architecture1 (LPA1) in rice (Oryza sativa) and its Arabidopsis homologues (SGR5/AtIDD15) have been reported to control plant architecture and auxin homeostasis. This study explores the role of LPA1 in determining lamina inclination in rice. LPA1 acts as a positive regulator to suppress lamina bending. Genetic and biochemical data indicate that LPA1 suppresses the auxin signalling that interacts with C-22-hydroxylated and 6-deoxo BRs, which regulates lamina inclination independently of OsBRI1. Mutant lpa1 plants are hypersensitive to indole-3-acetic acid (IAA) during the lamina inclination response, which is suppressed by the brassinazole (Brz) inhibitor of C-22 hydroxylase involved in BR synthesis. A strong synergic effect is detected between lpa1 and d2 (the defective mutant for catalysis of C-23-hydroxylated BRs) during IAA-mediated lamina inclination. No significant interaction between LPA1 and OsBRI1 was identified. The lpa1 mutant is sensitive to C-22-hydroxylated and 6-deoxo BRs in the d61-1 (rice BRI1 mutant) background. We present evidence verifying that two independent pathways function via either BRs or BRI1 to determine IAA-mediated lamina inclination in rice. RNA sequencing analysis and qRT-PCR indicate that LPA1 influences the expression of three OsPIN genes (OsPIN1a, OsPIN1c and OsPIN3a), which suggests that auxin flux might be an important factor in LPA1 mediated lamina inclination in rice. PMID- 26826220 TI - Climate and Developmental Plasticity: Interannual Variability in Grapevine Leaf Morphology. AB - The shapes of leaves are dynamic, changing over evolutionary time between species, within a single plant producing different shaped leaves at successive nodes, during the development of a single leaf as it allometrically expands, and in response to the environment. Notably, strong correlations between the dissection and size of leaves with temperature and precipitation exist in both the paleorecord and extant populations. Yet, a morphometric model integrating evolutionary, developmental, and environmental effects on leaf shape is lacking. Here, we continue a morphometric analysis of >5,500 leaves representing 270 grapevines of multiple Vitis species between two growing seasons. Leaves are paired one-to-one and vine-to-vine accounting for developmental context, between growing seasons. Linear discriminant analysis reveals shape features that specifically define growing season, regardless of species or developmental context. The shape feature, a more pronounced distal sinus, is associated with the colder, drier growing season, consistent with patterns observed in the paleorecord. We discuss the implications of such plasticity in a long-lived woody perennial, such as grapevine (Vitis spp.), with respect to the evolution and functionality of plant morphology and changes in climate. PMID- 26826221 TI - Xyloglucan Metabolism Differentially Impacts the Cell Wall Characteristics of the Endosperm and Embryo during Arabidopsis Seed Germination. AB - Cell wall remodeling is an essential mechanism for the regulation of plant growth and architecture, and xyloglucans (XyGs), the major hemicellulose, are often considered as spacers of cellulose microfibrils during growth. In the seed, the activity of cell wall enzymes plays a critical role in germination by enabling embryo cell expansion leading to radicle protrusion, as well as endosperm weakening prior to its rupture. A screen for Arabidopsis (Arabidopsis thaliana) mutants affected in the hormonal control of germination identified a mutant, xyl1, able to germinate on paclobutrazol, an inhibitor of gibberellin biosynthesis. This mutant also exhibited reduced dormancy and increased resistance to high temperature. The XYL1 locus encodes an alpha-xylosidase required for XyG maturation through the trimming of Xyl. The xyl1 mutant phenotypes were associated with modifications to endosperm cell wall composition that likely impact on its resistance, as further demonstrated by the restoration of normal germination characteristics by endosperm-specific XYL1 expression. The absence of phenotypes in mutants defective for other glycosidases, which trim Gal or Fuc, suggests that XYL1 plays the major role in this process. Finally, the decreased XyG abundance in hypocotyl longitudinal cell walls of germinating embryos indicates a potential role in cell wall loosening and anisotropic growth together with pectin de-methylesterification. PMID- 26826222 TI - Structural Redesigning Arabidopsis Lignins into Alkali-Soluble Lignins through the Expression of p-Coumaroyl-CoA:Monolignol Transferase PMT. AB - Grass lignins can contain up to 10% to 15% by weight of p-coumaric esters. This acylation is performed on monolignols under the catalysis of p-coumaroyl-coenzyme A monolignol transferase (PMT). To study the impact of p-coumaroylation on lignification, we first introduced the Brachypodium distachyon Bradi2g36910 (BdPMT1) gene into Arabidopsis (Arabidopsis thaliana) under the control of the constitutive maize (Zea mays) ubiquitin promoter. The resulting p-coumaroylation was far lower than that of lignins from mature grass stems and had no impact on stem lignin content. By contrast, introducing either the BdPMT1 or the Bradi1g36980 (BdPMT2) gene into Arabidopsis under the control of the Arabidopsis cinnamate-4-hydroxylase promoter boosted the p-coumaroylation of mature stems up to the grass lignin level (8% to 9% by weight), without any impact on plant development. The analysis of purified lignin fractions and the identification of diagnostic products confirmed that p-coumaric acid was associated with lignins. BdPMT1-driven p-coumaroylation was also obtained in the fah1 (deficient for ferulate 5-hydroxylase) and ccr1g (deficient for cinnamoyl-coenzyme A reductase) lines, albeit to a lower extent. Lignins from BdPMT1-expressing ccr1g lines were also found to be feruloylated. In Arabidopsis mature stems, substantial p coumaroylation of lignins was achieved at the expense of lignin content and induced lignin structural alterations, with an unexpected increase of lignin units with free phenolic groups. This higher frequency of free phenolic groups in Arabidopsis lignins doubled their solubility in alkali at room temperature. These findings suggest that the formation of alkali-leachable lignin domains rich in free phenolic groups is favored when p-coumaroylated monolignols participate in lignification in a grass in a similar manner. PMID- 26826223 TI - Feeding of Enterococcus faecium NCIMB 10415 Leads to Intestinal miRNA-423-5p Induced Regulation of Immune-Relevant Genes. AB - Probiotics are widely used in human and animal health, but little is known about the mode of action of probiotics. One possible mechanism at the molecular level could be an influence on microRNAs (miRNAs) and the related immune-relevant target genes. Here, we analyzed differential expression of miRNA and potential target genes of ileal and jejunal lymphatic tissues from Enterococcus faeciumNCIMB 10415-fed piglets versus untreated controls by using next-generation sequencing. We identified miR-423-5p as being greatly affected by the treatment group (2.32-fold;P= 0.014). Validation by reverse transcription-quantitative PCR (RT-qPCR) confirmed a significant upregulation of miR-423-5p (2.11-fold;P= 0.03) and, additionally, downregulation of the important immune-relevant immunoglobulin lambda light C region (IGLC) (0.61-fold;P= 0.03) and immunoglobulin kappa constant (IGKC) (0.69-fold;P= 0.04) target genes. Expression analysis of miR-423 5p and IGLC at different age points shows a clear anti correlated relationship. Luciferase reporter assays with a HeLa cell line verified IGLC as a target of miR 423-5p. The results provided evidence for an effect of feeding of E. faeciumon the expression of miR-423-5p and on the regulation of the IGLC gene through miR 423-5p. This might be a possible mode of action of E. faeciumon immune cell regulation in the small intestine. PMID- 26826224 TI - Ecological Genomics of the Uncultivated Marine Roseobacter Lineage CHAB-I-5. AB - Members of the marine Roseobacter clade are major participants in global carbon and sulfur cycles. While roseobacters are well represented in cultures, several abundant pelagic lineages, including SAG-O19, DC5-80-3, and NAC11-7, remain largely uncultivated and show evidence of genome streamlining. Here, we analyzed the partial genomes of three single cells affiliated with CHAB-I-5, another abundant but exclusively uncultivated Roseobacter lineage. Members of this lineage encode several metabolic potentials that are absent in streamlined genomes. Examples are quorum sensing and type VI secretion systems, which enable them to effectively interact with host and other bacteria. Further analysis of the CHAB-I-5 single-cell amplified genomes (SAGs) predicted that this lineage comprises members with relatively large genomes (4.1 to 4.4 Mbp) and a high fraction of noncoding DNA (10 to 12%), which is similar to what is observed in many cultured, nonstreamlined Roseobacter lineages. The four uncultured lineages, while exhibiting highly variable geographic distributions, together represent >60% of the global pelagic roseobacters. They are consistently enriched in genes encoding the capabilities of light harvesting, oxidation of "energy-rich" reduced sulfur compounds and methylated amines, uptake and catabolism of various carbohydrates and osmolytes, and consumption of abundant exudates from phytoplankton. These traits may define the global prevalence of the four lineages among marine bacterioplankton. PMID- 26826226 TI - Lack of Involvement of Fenton Chemistry in Death of Methicillin-Resistant and Methicillin-Sensitive Strains of Staphylococcus aureus and Destruction of Their Genomes on Wet or Dry Copper Alloy Surfaces. AB - The pandemic of hospital-acquired infections caused by methicillin-resistant Staphylococcus aureus (MRSA) has declined, but the evolution of strains with enhanced virulence and toxins and the increase of community-associated infections are still a threat. In previous studies, 10(7) MRSA bacteria applied as simulated droplet contamination were killed on copper and brass surfaces within 90 min. However, contamination of surfaces is often via finger tips and dries rapidly, and it may be overlooked by cleaning regimes (unlike visible droplets). In this new study, a 5-log reduction of a hardy epidemic strain of MRSA (epidemic methicillin-resistant S. aureus 16 [EMRSA-16]) was observed following 10 min of contact with copper, and a 4-log reduction was observed on copper nickel and cartridge brass alloys in 15 min. A methicillin-sensitive S. aureus (MSSA) strain from an osteomyelitis patient was killed on copper surfaces in 15 min, and 4-log and 3-log reductions occurred within 20 min of contact with copper nickel and cartridge brass, respectively. Bacterial respiration was compromised on copper surfaces, and superoxide was generated as part of the killing mechanism. In addition, destruction of genomic DNA occurs on copper and brass surfaces, allaying concerns about horizontal gene transfer and copper resistance. Incorporation of copper alloy biocidal surfaces may help to reduce the spread of this dangerous pathogen. PMID- 26826225 TI - Thermal Inactivation of Enteric Viruses and Bioaccumulation of Enteric Foodborne Viruses in Live Oysters (Crassostrea virginica). AB - Human enteric viruses are among the main causative agents of shellfish-associated outbreaks. In this study, the kinetics of viral bioaccumulation in live oysters and the heat stabilities of the predominant enteric viruses were determined both in tissue culture and in oyster tissues. A human norovirus (HuNoV) GII.4 strain, HuNoV surrogates (murine norovirus [MNV-1], Tulane virus [TV]), hepatitis A virus (HAV), and human rotavirus (RV) bioaccumulated to high titers within oyster tissues, with different patterns of bioaccumulation for the different viruses. We tested the thermal stability of each virus at 62, 72, and 80 degrees C in culture medium. The viruses can be ranked from the most heat resistant to the least stable as follows: HAV, RV, TV, MNV-1. In addition, we found that oyster tissues provided protection to the viruses during heat treatment. To decipher the mechanism underlying viral inactivation by heat, purified TV was treated at 80 degrees C for increasing time intervals. It was found that the integrity of the viral capsid was disrupted, whereas viral genomic RNA remained intact. Interestingly, heat treatment leading to complete loss of TV infectivity was not sufficient to completely disrupt the receptor binding activity of TV, as determined by the porcine gastric mucin-magnetic bead binding assay. Similarly, HuNoV virus-like particles (VLPs) and a HuNoV GII.4 strain retained some receptor binding ability following heat treatment. Although foodborne viruses have variable heat stability, 80 degrees C for >6 min was sufficient to completely inactivate enteric viruses in oysters, with the exception of HAV. PMID- 26826227 TI - Alcaligenes faecalis ZD02, a Novel Nematicidal Bacterium with an Extracellular Serine Protease Virulence Factor. AB - Root knot nematodes (RKNs) are the world's most damaging plant-parasitic nematodes (PPNs), and they can infect almost all crops. At present, harmful chemical nematicides are applied to control RKNs. Using microbial nematicides has been proposed as a better management strategy than chemical control. In this study, we describe a novel nematicidal bacterium named Alcaligenes faecalis ZD02. A. faecalis ZD02 was isolated from Caenorhabditis elegans cadavers and has nematostatic and nematicidal activity, as confirmed by C. elegans growth assay and life span assay. In addition, A. faecalis ZD02 fermentation broth showed toxicity against C. elegans and Meloidogyne incognita. To identify the nematicidal virulence factor, the genome of strain ZD02 was sequenced. By comparing all of the predicted proteins of strain ZD02 to reported nematicidal virulence factors, we determined that an extracellular serine protease (Esp) has potential to be a nematicidal virulence factor, which was confirmed by bioassay on C. elegans and M. incognita. Using C. elegans as the target model, we found that both A. faecalis ZD02 and the virulence factor Esp can damage the intestines of C. elegans. The discovery that A. faecalis ZD02 has nematicidal activity provides a novel bacterial resource for the control of RKNs. PMID- 26826228 TI - Plasmidic Expression of nemA and yafC* Increased Resistance of Ethanologenic Escherichia coli LY180 to Nonvolatile Side Products from Dilute Acid Treatment of Sugarcane Bagasse and Artificial Hydrolysate. AB - Hydrolysate-resistant Escherichia coli SL100 was previously isolated from ethanologenic LY180 after sequential transfers in AM1 medium containing a dilute acid hydrolysate of sugarcane bagasse and was used as a source of resistance genes. Many genes that affect tolerance to furfural, the most abundant inhibitor, have been described previously. To identify genes associated with inhibitors other than furfural, plasmid clones were selected in an artificial hydrolysate that had been treated with a vacuum to remove furfural. Two new resistance genes were discovered from Sau3A1 libraries of SL100 genomic DNA: nemA (N ethylmaleimide reductase) and a putative regulatory gene containing a mutation in the coding region, yafC*. The presence of these mutations in SL100 was confirmed by sequencing. A single mutation was found in the upstream regulatory region of nemR (nemRA operon) in SL100. This mutation increased nemA activity 20-fold over that of the parent organism (LY180) in AM1 medium without hydrolysate and increased nemA mRNA levels >200-fold. Addition of hydrolysates induced nemA expression (mRNA and activity), in agreement with transcriptional control. NemA activity was stable in cell extracts (9 h, 37 degrees C), eliminating a role for proteinase in regulation. LY180 with a plasmid expressing nemA or yafC* was more resistant to a vacuum-treated sugarcane bagasse hydrolysate and to a vacuum treated artificial hydrolysate than LY180 with an empty-vector control. Neither gene affected furfural tolerance. The vacuum-treated hydrolysates inhibited the reduction of N-ethylmaleimide by NemA while also serving as substrates. Expression of the nemA or yafC* plasmid in LY180 doubled the rate of ethanol production from the vacuum-treated sugarcane bagasse hydrolysate. PMID- 26826229 TI - Airborne and Grain Dust Fungal Community Compositions Are Shaped Regionally by Plant Genotypes and Farming Practices. AB - Chronic exposure to airborne fungi has been associated with different respiratory symptoms and pathologies in occupational populations, such as grain workers. However, the homogeneity in the fungal species composition of these bioaerosols on a large geographical scale and the different drivers that shape these fungal communities remain unclear. In this study, the diversity of fungi in grain dust and in the aerosols released during harvesting was determined across 96 sites at a geographical scale of 560 km(2) along an elevation gradient of 500 m by tag encoded 454 pyrosequencing of the internal transcribed spacer (ITS) sequences. Associations between the structure of fungal communities in the grain dust and different abiotic (farming system, soil characteristics, and geographic and climatic parameters) and biotic (wheat cultivar and previous crop culture) factors were explored. These analyses revealed a strong relationship between the airborne and grain dust fungal communities and showed the presence of allergenic and mycotoxigenic species in most samples, which highlights the potential contribution of these fungal species to work-related respiratory symptoms of grain workers. The farming system was the major driver of the alpha and beta phylogenetic diversity values of fungal communities. In addition, elevation and soil CaCO3 concentrations shaped the alpha diversity, whereas wheat cultivar, cropping history, and the number of freezing days per year shaped the taxonomic beta diversity of these communities. PMID- 26826231 TI - Improved Acetic Acid Resistance in Saccharomyces cerevisiae by Overexpression of the WHI2 Gene Identified through Inverse Metabolic Engineering. AB - Development of acetic acid-resistant Saccharomyces cerevisiae is important for economically viable production of biofuels from lignocellulosic biomass, but the goal remains a critical challenge due to limited information on effective genetic perturbation targets for improving acetic acid resistance in the yeast. This study employed a genomic-library-based inverse metabolic engineering approach to successfully identify a novel gene target, WHI2 (encoding a cytoplasmatic globular scaffold protein), which elicited improved acetic acid resistance in S. cerevisiae. Overexpression of WHI2 significantly improved glucose and/or xylose fermentation under acetic acid stress in engineered yeast. The WHI2 overexpressing strain had 5-times-higher specific ethanol productivity than the control in glucose fermentation with acetic acid. Analysis of the expression of WHI2 gene products (including protein and transcript) determined that acetic acid induced endogenous expression of Whi2 in S. cerevisiae. Meanwhile, the whi2Delta mutant strain had substantially higher susceptibility to acetic acid than the wild type, suggesting the important role of Whi2 in the acetic acid response in S. cerevisiae. Additionally, overexpression of WHI2 and of a cognate phosphatase gene, PSR1, had a synergistic effect in improving acetic acid resistance, suggesting that Whi2 might function in combination with Psr1 to elicit the acetic acid resistance mechanism. These results improve our understanding of the yeast response to acetic acid stress and provide a new strategy to breed acetic acid resistant yeast strains for renewable biofuel production. PMID- 26826230 TI - A Highly Arginolytic Streptococcus Species That Potently Antagonizes Streptococcus mutans. AB - The ability of certain oral biofilm bacteria to moderate pH through arginine metabolism by the arginine deiminase system (ADS) is a deterrent to the development of dental caries. Here, we characterize a novel Streptococcus strain, designated strain A12, isolated from supragingival dental plaque of a caries-free individual. A12 not only expressed the ADS pathway at high levels under a variety of conditions but also effectively inhibited growth and two intercellular signaling pathways of the dental caries pathogen Streptococcus mutans. A12 produced copious amounts of H2O2 via the pyruvate oxidase enzyme that were sufficient to arrest the growth of S. mutans. A12 also produced a protease similar to challisin (Sgc) of Streptococcus gordonii that was able to block the competence-stimulating peptide (CSP)-ComDE signaling system, which is essential for bacteriocin production by S. mutans. Wild-type A12, but not an sgc mutant derivative, could protect the sensitive indicator strain Streptococcus sanguinis SK150 from killing by the bacteriocins of S. mutans. A12, but not S. gordonii, could also block the XIP (comX-inducing peptide) signaling pathway, which is the proximal regulator of genetic competence in S. mutans, but Sgc was not required for this activity. The complete genome sequence of A12 was determined, and phylogenomic analyses compared A12 to streptococcal reference genomes. A12 was most similar to Streptococcus australis and Streptococcus parasanguinis but sufficiently different that it may represent a new species. A12-like organisms may play crucial roles in the promotion of stable, health-associated oral biofilm communities by moderating plaque pH and interfering with the growth and virulence of caries pathogens. PMID- 26826232 TI - Genome Content and Phylogenomics Reveal both Ancestral and Lateral Evolutionary Pathways in Plant-Pathogenic Streptomyces Species. AB - Streptomyces spp. are highly differentiated actinomycetes with large, linear chromosomes that encode an arsenal of biologically active molecules and catabolic enzymes. Members of this genus are well equipped for life in nutrient-limited environments and are common soil saprophytes. Out of the hundreds of species in the genus Streptomyces, a small group has evolved the ability to infect plants. The recent availability of Streptomyces genome sequences, including four genomes of pathogenic species, provided an opportunity to characterize the gene content specific to these pathogens and to study phylogenetic relationships among them. Genome sequencing, comparative genomics, and phylogenetic analysis enabled us to discriminate pathogenic from saprophytic Streptomyces strains; moreover, we calculated that the pathogen-specific genome contains 4,662 orthologs. Phylogenetic reconstruction suggested that Streptomyces scabies and S. ipomoeae share an ancestor but that their biosynthetic clusters encoding the required virulence factor thaxtomin have diverged. In contrast, S. turgidiscabies and S. acidiscabies, two relatively unrelated pathogens, possess highly similar thaxtomin biosynthesis clusters, which suggests that the acquisition of these genes was through lateral gene transfer. PMID- 26826233 TI - Photobacterium angustum and Photobacterium kishitanii, Psychrotrophic High-Level Histamine-Producing Bacteria Indigenous to Tuna. AB - Scombrotoxin fish poisoning (SFP) remains the main contributor of fish poisoning incidents in the United States, despite efforts to control its spread. Psychrotrophic histamine-producing bacteria (HPB) indigenous to scombrotoxin forming fish may contribute to the incidence of SFP. We examined the gills, skin, and anal vents of yellowfin (n = 3), skipjack (n = 1), and albacore (n = 6) tuna for the presence of indigenous HPB. Thirteen HPB strains were isolated from the anal vent samples from albacore (n = 3) and yellowfin (n = 2) tuna. Four of these isolates were identified as Photobacterium kishitanii and nine isolates as Photobacterium angustum; these isolates produced 560 to 603 and 1,582 to 2,338 ppm histamine in marine broth containing 1% histidine (25 degrees C for 48 h), respectively. The optimum growth temperatures and salt concentrations were 26 to 27 degrees C and 1% salt for P. kishitanii and 30 to 32 degrees C and 2% salt for P. angustum in Luria 70% seawater (LSW-70). The optimum activity of the HDC enzyme was at 15 to 30 degrees C for both species. At 5 degrees C, P. kishitanii and P. angustum had growth rates of 0.1 and 0.2 h(-1), respectively, and the activities of histidine decarboxylase (HDC) enzymes were 71% and 63%, respectively. These results show that indigenous HPB in tuna are capable of growing at elevated and refrigeration temperatures. These findings demonstrate the need to examine the relationships between the rate of histamine production at refrigeration temperatures, seafood shelf life, and regulatory limits. PMID- 26826234 TI - Activity-Based Protein Profiling of Ammonia Monooxygenase in Nitrosomonas europaea. AB - Nitrosomonas europaea is an aerobic nitrifying bacterium that oxidizes ammonia (NH3) to nitrite (NO2 (-)) through the sequential activities of ammonia monooxygenase (AMO) and hydroxylamine dehydrogenase (HAO). Many alkynes are mechanism-based inactivators of AMO, and here we describe an activity-based protein profiling method for this enzyme using 1,7-octadiyne (17OD) as a probe. Inactivation of NH4 (+)-dependent O2 uptake by N. europaea by 17OD was time- and concentration-dependent. The effects of 17OD were specific for ammonia-oxidizing activity, andde novoprotein synthesis was required to reestablish this activity after cells were exposed to 17OD. Cells were reacted with Alexa Fluor 647 azide using a copper-catalyzed azide-alkyne cycloaddition (CuAAC) (click) reaction, solubilized, and analyzed by SDS-PAGE and infrared (IR) scanning. A fluorescent 28-kDa polypeptide was observed for cells previously exposed to 17OD but not for cells treated with either allylthiourea or acetylene prior to exposure to 17OD or for cells not previously exposed to 17OD. The fluorescent polypeptide was membrane associated and aggregated when heated with beta-mercaptoethanol and SDS. The fluorescent polypeptide was also detected in cells pretreated with other diynes, but not in cells pretreated with structural homologs containing a single ethynyl functional group. The membrane fraction from 17OD-treated cells was conjugated with biotin-azide and solubilized in SDS. Streptavidin affinity purified polypeptides were on-bead trypsin-digested, and amino acid sequences of the peptide fragments were determined by liquid chromatography-mass spectrometry (LC-MS) analysis. Peptide fragments from AmoA were the predominant peptides detected in 17OD-treated samples. In-gel digestion and matrix-assisted laser desorption ionization-tandem time of flight (MALDI-TOF/TOF) analyses also confirmed that the fluorescent 28-kDa polypeptide was AmoA. PMID- 26826236 TI - Using the capability approach to understand the determinants of subjective well being among community-dwelling older people in New Zealand. AB - BACKGROUND: as the longevity of the population increases, attention has turned to quality of life of older people as a component of healthy ageing. The objective of this study was to use Welch Saleeby's model of the capability approach to explore the determinants of subjective well-being among older people. METHODS: this analysis used data from a sample of older people, aged 50-87, from 2012 wave of the New Zealand Longitudinal Study of Ageing (NZLSA) (n = 2,793). Structural equation modelling was used to examine the relationships between the commodities (number of chronic conditions reported, physical and mental health), and personal and environmental factors (economic living standard and discrimination), on the capabilities of older people to achieve well-being. RESULTS: the findings supported Welch Saleeby's model. Capabilities mediated the relationship between commodities and well-being, indicating that increasing the range of real opportunities available to older people is a key step in increasing well-being. Age and gender were also found to be significant moderators of these relationships. The relationship between economic living standards and well-being was weakest for the oldest participants, but experiences of discrimination had a stronger effect on well-being in this age group. CONCLUSION: Welch Saleeby's model of the capability approach provides a useful framework for advancing the ethics of care as it highlights the multidimensional nature of well-being in later life. Focusing on expanding capabilities for older people enables policymakers and practitioners to understand the resources and supports required to enable well-being in the context of health challenges. PMID- 26826235 TI - Heterogeneity in Induction Level, Infection Ability, and Morphology of Shiga Toxin-Encoding Phages (Stx Phages) from Dairy and Human Shiga Toxin-Producing Escherichia coli O26:H11 Isolates. AB - Shiga toxin (Stx)-producing Escherichia coli (STEC) bacteria are foodborne pathogens responsible for diarrhea and hemolytic-uremic syndrome (HUS). Shiga toxin, the main STEC virulence factor, is encoded by the stx gene located in the genome of a bacteriophage inserted into the bacterial chromosome. The O26:H11 serotype is considered to be the second-most-significant HUS-causing serotype worldwide after O157:H7. STEC O26:H11 bacteria and their stx-negative counterparts have been detected in dairy products. They may convert from the one form to the other by loss or acquisition of Stx phages, potentially confounding food microbiological diagnostic methods based on stx gene detection. Here we investigated the diversity and mobility of Stx phages from human and dairy STEC O26:H11 strains. Evaluation of their rate of in vitro induction, occurring either spontaneously or in the presence of mitomycin C, showed that the Stx2 phages were more inducible overall than Stx1 phages. However, no correlation was found between the Stx phage levels produced and the origin of the strains tested or the phage insertion sites. Morphological analysis by electron microscopy showed that Stx phages from STEC O26:H11 displayed various shapes that were unrelated to Stx1 or Stx2 types. Finally, the levels of sensitivity of stx-negative E. coli O26:H11 to six Stx phages differed among the 17 strains tested and our attempts to convert them into STEC were unsuccessful, indicating that their lysogenization was a rare event. PMID- 26826237 TI - Sex on the brain! Associations between sexual activity and cognitive function in older age. AB - BACKGROUND: the relationship between cognition and sexual activity in healthy older adults is under-researched. A limited amount of research in this area has shown that sexual activity is associated with better cognition in older men. The current study explores the possible mediating factors in this association in men and women, and attempts to provide an explanation in terms of physiological influences on cognitive function. METHODS: using newly available data from Wave 6 of the English Longitudinal Study of Ageing, the current study explored associations between sexual activity and cognition in adults aged 50-89 (n = 6,833). Two different tests of cognitive function were analysed: number sequencing, which broadly relates to executive function, and word recall, which broadly relates to memory. RESULTS: after adjusting for age, education, wealth, physical activity, depression, cohabiting, self-rated health, loneliness and quality of life, there were significant associations between sexual activity and number sequencing and recall in men. However, in women there was a significant association between sexual activity and recall, but not number sequencing. CONCLUSIONS: possible mediators of these associations (e.g. neurotransmitters) are discussed. The cross-sectional nature of the analysis is limiting, but provides a promising avenue for future explorations and longitudinal studies. The findings have implications for the promotion of sexual counselling in healthcare settings, where maintaining a healthy sex life in older age could be instrumental in improving cognitive function and well-being. PMID- 26826239 TI - Vitamin C Facilitates Demethylation of the Foxp3 Enhancer in a Tet-Dependent Manner. AB - Demethylation of CpG motifs in the Foxp3 intronic element, conserved noncoding sequence 2 (CNS2), is indispensable for the stable expression of Foxp3 in regulatory T cells (Tregs). In this study, we found that vitamin C induces CNS2 demethylation in Tregs in a ten-eleven-translocation 2 (Tet2)-dependent manner. The CpG motifs of CNS2 in Tregs generated in vitro by TGF-beta (iTregs), which were methylated originally, became demethylated after vitamin C treatment. The conversion of 5-methylcytosin into 5-hydroxymethylcytosin was more efficient, and the methyl group from the CpG motifs of Foxp3 CNS2 was erased rapidly in iTregs treated with vitamin C. The effect of vitamin C disappeared in Tet2(-/-) iTregs. Furthermore, CNS2 in peripheral Tregs in vivo, which were demethylated originally, became methylated after treatment with a sodium-dependent vitamin C transporter inhibitor, sulfinpyrazone. Finally, CNS2 demethylation in thymic Tregs was also impaired in Tet2(-/-) mice, but not in wild type mice, when they were treated with sulfinpyrazone. Collectively, vitamin C was required for the CNS2 demethylation mediated by Tet proteins, which was essential for Foxp3 expression. Our findings indicate that environmental factors, such as nutrients, could bring about changes in immune homeostasis through epigenetic mechanisms. PMID- 26826240 TI - MicroRNA-30c Modulates Type I IFN Responses To Facilitate Porcine Reproductive and Respiratory Syndrome Virus Infection by Targeting JAK1. AB - Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen and has evolved several mechanisms to evade IFN-I responses. We report that a host microRNA, miR-30c, was upregulated by PRRSV via activating NF-kappaB and facilitated its ability to infect subject animals. Subsequently, we demonstrated that miR-30c was a potent negative regulator of IFN-I signaling by targeting JAK1, resulting in the enhancement of PRRSV infection. In addition, we found that JAK1 expression was significantly decreased by PRRSV and recovered when miR-30c inhibitor was overexpressed. Importantly, miR-30c was also upregulated by PRRSV infection in vivo, and miR-30c expression corresponded well with viral loads in lungs and porcine alveolar macrophages of PRRSV-infected pigs. Our findings identify a new strategy taken by PRRSV to escape IFN-I mediated antiviral immune responses by engaging miR-30c and, thus, improve our understanding of its pathogenesis. PMID- 26826238 TI - Despite Increased Type 1 IFN, Autoimmune Nonobese Diabetic Mice Display Impaired Dendritic Cell Response to CpG and Decreased Nuclear Localization of IFN Activated STAT1. AB - Innate immune signals help break self-tolerance to initiate autoimmune diseases such as type 1 diabetes, but innate contributions to subsequent regulation of disease progression are less clear. Most studies have measured in vitro innate responses of GM-CSF dendritic cells (DCs) that are functionally distinct from conventional DCs (cDCs) and do not reflect in vivo DC subsets. To determine whether autoimmune NOD mice have alterations in type 1 IFN innate responsiveness, we compared cDCs from prediabetic NOD and control C57BL/6 (B6) mice stimulated in vivo with the TLR9 ligand CpG, a strong type 1 IFN inducer. In response to CpG, NOD mice produce more type 1 IFN and express higher levels of CD40, and NOD monocyte DCs make more TNF. However, the overall CpG-induced transcriptional response is muted in NOD cDCs. Of relevance the costimulatory proteins CD80/CD86, signals needed for regulatory T cell homeostasis, are upregulated less on NOD cDCs. Interestingly, NOD Rag1(-/-) mice also display a defect in CpG-induced CD86 upregulation compared with B6 Rag1(-/-), indicating this particular innate alteration precedes adaptive autoimmunity. The impaired response in NOD DCs is likely downstream of the IFN-alpha/beta receptor because DCs from NOD and B6 mice show similar CpG-induced CD86 levels when anti-IFN-alpha/beta receptor Ab is added. IFN-alpha-induced nuclear localization of activated STAT1 is markedly reduced in NOD CD11c(+) cells, consistent with lower type 1 IFN responsiveness. In conclusion, NOD DCs display altered innate responses characterized by enhanced type 1 IFN and activation of monocyte-derived DCs but diminished cDC type 1 IFN response. PMID- 26826241 TI - Hepatitis C Virus-Induced Myeloid-Derived Suppressor Cells Suppress NK Cell IFN gamma Production by Altering Cellular Metabolism via Arginase-1. AB - The hepatitis C virus (HCV) infects ~ 200 million people worldwide. The majority of infected individuals develop persistent infection, resulting in chronic inflammation and liver disease, including cirrhosis and hepatocellular carcinoma. The ability of HCV to establish persistent infection is partly due to its ability to evade the immune response through multiple mechanisms, including suppression of NK cells. NK cells control HCV replication during the early phase of infection and regulate the progression to chronic disease. In particular, IFN-gamma produced by NK cells limits viral replication in hepatocytes and is important for the initiation of adaptive immune responses. However, NK cell function is significantly impaired in chronic HCV patients. The cellular and molecular mechanisms responsible for impaired NK cell function in HCV infection are not well defined. In this study, we analyzed the interaction of human NK cells with CD33(+) PBMCs that were exposed to HCV. We found that NK cells cocultured with HCV-conditioned CD33(+) PBMCs produced lower amounts of IFN-gamma, with no effect on granzyme B production or cell viability. Importantly, this suppression of NK cell-derived IFN-gamma production was mediated by CD33(+)CD11b(lo)HLA-DR(lo) myeloid-derived suppressor cells (MDSCs) via an arginase-1-dependent inhibition of mammalian target of rapamycin activation. Suppression of IFN-gamma production was reversed by l-arginine supplementation, consistent with increased MDSC arginase-1 activity. These novel results identify the induction of MDSCs in HCV infection as a potent immune evasion strategy that suppresses antiviral NK cell responses, further indicating that blockade of MDSCs may be a potential therapeutic approach to ameliorate chronic viral infections in the liver. PMID- 26826242 TI - Autoreactive T Cells from Patients with Myasthenia Gravis Are Characterized by Elevated IL-17, IFN-gamma, and GM-CSF and Diminished IL-10 Production. AB - Myasthenia gravis (MG) is a prototypical autoimmune disease that is among the few for which the target Ag and the pathogenic autoantibodies are clearly defined. The pathology of the disease is affected by autoantibodies directed toward the acetylcholine receptor (AChR). Mature, Ag-experienced B cells rely on the action of Th cells to produce these pathogenic Abs. The phenotype of the MG Ag-reactive T cell compartment is not well defined; thus, we sought to determine whether such cells exhibit both a proinflammatory and a pathogenic phenotype. A novel T cell library assay that affords multiparameter interrogation of rare Ag-reactive CD4(+) T cells was applied. Proliferation and cytokine production in response to both AChR and control Ags were measured from 3120 T cell libraries derived from 11 MG patients and paired healthy control subjects. The frequency of CCR6(+) memory T cells from MG patients proliferating in response to AChR-derived peptides was significantly higher than that of healthy control subjects. Production of both IFN-gamma and IL-17, in response to AChR, was also restricted to the CCR6(+) memory T cell compartment in the MG cohort, indicating a proinflammatory phenotype. These T cells also included an elevated expression of GM-CSF and absence of IL-10 expression, indicating a proinflammatory and pathogenic phenotype. This component of the autoimmune response in MG is of particular importance when considering the durability of MG treatment strategies that eliminate B cells, because the autoreactive T cells could renew autoimmunity in the reconstituted B cell compartment with ensuing clinical manifestations. PMID- 26826243 TI - CD4+ Group 1 Innate Lymphoid Cells (ILC) Form a Functionally Distinct ILC Subset That Is Increased in Systemic Sclerosis. AB - Innate lymphoid cells (ILC) are a heterogeneous group of cellular subsets that produce large amounts of T cell-associated cytokines in response to innate stimulation in the absence of Ag. In this study, we define distinct patterns of surface marker and cytokine expression among the ILC subsets that may further delineate their migration and function. Most notably, we found that the subset previously defined as group 1 ILC (ILC1) contains CD4(+) CD8(-), CD4(-) CD8(+), and CD4(-) CD8(-) populations. Although all ILC1 subsets shared characteristics with Th1 cells, CD4(+) ILC1 also demonstrated significant phenotypic and functional heterogeneity. We also show that the frequencies of CD4(+) ILC1 and NKp44(+) group 3 ILC, but not CD4(-) ILC1 or group 2 ILC, are increased in the peripheral blood of individuals with systemic sclerosis (SSc), a disease characterized by fibrotic and vascular pathology, as well as immune dysregulation. Furthermore, we demonstrate that CD4(+) and CD4(-) ILC1 are functionally divergent based on their IL-6Ralpha expression and that the frequency of IL-6Ralpha expression on ILC is altered in SSc. The distinct phenotypic and functional features of CD4(+) and CD4(-) ILC1 suggest that they may have differing roles in the pathogenesis of immune-mediated diseases, such as SSc. PMID- 26826244 TI - Cutting Edge: Critical Role of Glycolysis in Human Plasmacytoid Dendritic Cell Antiviral Responses. AB - Plasmacytoid dendritic cells (pDCs) are vital to antiviral defense, directing immune responses via secretion of huge concentrations of IFN-alpha. These cells are critical in protecting the lung against clinically relevant respiratory viruses, particularly influenza (Flu), a virus responsible for substantial worldwide morbidity and mortality. How pDC responses to such viral pathogens are regulated, however, is poorly understood in humans. Using an unbiased approach of gene chip analysis, we discovered that Flu significantly affects metabolism in primary human pDCs. We demonstrate that Flu and RV, another common respiratory virus, induce glycolysis in pDCs and that this metabolic pathway regulates pDC antiviral functions, including IFN-alpha production and phenotypic maturation. Intranasal vaccination of human volunteers with live influenza virus also increases glycolysis in circulating pDCs, highlighting a previously unrecognized potential role for metabolism in regulating pDC immune responses to viral infections in humans. PMID- 26826245 TI - Clusterin Modulates Allergic Airway Inflammation by Attenuating CCL20-Mediated Dendritic Cell Recruitment. AB - Recruitment and activation of dendritic cells (DCs) in the lungs are critical for Th2 responses in asthma, and CCL20 secreted from bronchial epithelial cells (BECs) is known to influence the recruitment of DCs. Because asthma is a disease that is closely associated with oxidative stress, we hypothesized that clusterin, an oxidative stress regulatory molecule, may have a role in the development of allergic airway inflammation. The aim of this study was to examine whether clusterin regulates CCL20 production from the BECs and the subsequent DC recruitment in the lungs. To verify the idea, clusterin knockout (Clu(-/-)), clusterin heterogeneous (Clu(+/-)), and wild-type mice were exposed intranasally to house dust mite (HDM) extract to induce allergic airway inflammation. We found that the total number of immune cells in bronchoalveolar lavage fluid and the lung was increased in Clu(-/-) and Clu(+/-) mice. Of these immune cells, inflammatory DCs (CD11b(+)CD11c(+)) and Ly6C(high) monocyte populations in the lung were significantly increased, which was accompanied by increased levels of various chemokines, including CCL20 in bronchoalveolar lavage fluid, and increased oxidative stress markers in the lung. Moreover, HDM-stimulated human BECs with either up- or downregulated clusterin expression showed that CCL20 secretion was negatively associated with clusterin expression. Interestingly, clusterin also reduced the level of intracellular reactive oxygen species, which is related to induction of CCL20 expression after HDM stimulation. Thus, the antioxidant property of clusterin is suggested to regulate the expression of CCL20 in BECs and the subsequent recruitment of inflammatory DCs in the airway. PMID- 26826246 TI - Enhancement of Microbiota in Healthy Macaques Results in Beneficial Modulation of Mucosal and Systemic Immune Function. AB - Given the critical role of mucosal surfaces in susceptibility to infection, it is imperative that effective mucosal responses are induced when developing efficacious vaccines and prevention strategies for infection. Modulating the microbiota in the gastrointestinal (GI) tract through the use of probiotics (PBio) is a safe and well-tolerated approach to enhance mucosal and overall health. We assessed the longitudinal impact of daily treatment with the VSL#3 probiotic on cellular and humoral immunity and inflammation in healthy macaques. PBio therapy resulted in significantly increased frequencies of B cells expressing IgA in the colon and lymph node (LN), likely because of significantly increased LN T follicular helper cell frequencies and LN follicles. Increased frequencies of IL-23(+) APCs in the colon were found post-PBio treatment, which correlated with LN T follicular helper cells. Finally, VSL#3 significantly downmodulated the response of TLR2-, TLR3-, TLR4-, and TLR9-expressing HEK293 cells to stimulation with Pam3CSK4, polyinosinic-polycytidylic acid, LPS, and ODN2006, respectively. These data provide a mechanism for the beneficial impact of PBio on mucosal health and implicates the use of PBio therapy in the context of vaccination or preventative approaches to enhance protection from mucosal infection by improving immune defenses at the mucosal portal of entry. PMID- 26826248 TI - HB-EGF-Promoted Airway Smooth Muscle Cells and Their Progenitor Migration Contribute to Airway Smooth Muscle Remodeling in Asthmatic Mouse. AB - The airway smooth muscle (ASM) cells' proliferation, migration, and their progenitor's migration are currently regarded as causative factors for ASM remodeling in asthma. Heparin-binding epidermal growth factor (HB-EGF), a potent mitogen and chemotactic factor, could promote ASM cell proliferation through MAPK pathways. In this study, we obtained primary ASM cells and their progenitors from C57BL/6 mice and went on to explore the role of HB-EGF in these cells migration and the underlying mechanisms. We found that recombinant HB-EGF (rHB-EGF) intratracheal instillation accelerated ASM layer thickening in an OVA-induced asthmatic mouse. Modified Boyden chamber assay revealed that rHB-EGF facilitate ASM cell migration in a dose-dependent manner and ASM cells from asthmatic mice had a greater migration ability than that from normal counterparts. rHB-EGF could stimulate the phosphorylation of ERK1/2 and p38 in ASM cells but further migration assay showed that only epidermal growth factor receptor inhibitor (AG1478) or p38 inhibitor (SB203580), but not ERK1/2 inhibitor (PD98059), could inhibit rHB-EGF-mediated ASM cells migration. Actin cytoskeleton experiments exhibited that rHB-EGF could cause actin stress fibers disassembly and focal adhesions formation of ASM cells through the activation of p38. Finally, airway instillation of rHB-EGF promoted the recruitment of bone marrow-derived smooth muscle progenitor cells, which were transferred via caudal vein, migrating into the airway from the circulation. These observations demonstrated that ASM remodeling in asthma might have resulted from HB-EGF-mediated ASM cells and their progenitor cells migration, via p38 MAPK-dependent actin cytoskeleton remodeling. PMID- 26826247 TI - Overlapping IgG4 Responses to Self- and Environmental Antigens in Endemic Pemphigus Foliaceus. AB - The etiology of human autoimmune diseases in general remains largely unknown, although the genetic and environmental interplay may be relevant. This applies to the autoimmune diseases of the skin such as the pemphigus phenotypes and others. In this group, there is an endemic form of pemphigus foliaceus (also known as fogo selvagem [FS]) in which the pathogenic IgG4 autoantibody response to the self-antigen desmoglein 1 (Dsg1) cross-reacts with the LJM11 sand fly salivary gland Ag. In this investigation, we dissected the IgG4 autoantibody repertoires used by FS patients in response to endogenous self-Dsg1 and exogenous LJM11 sand fly Ag. Based on analyses of the genetic clonal signatures of these Abs, our results indicate that there is a significant overlap between these two responses, as all identified IgG4 mAbs cross-react to both Dsg1 and LJM11 Ags. Germline H- and L-chain V gene Abs generated according to mutated cross-reactive mAbs preserved their reactivity to both Ags. Our findings suggest that both Dsg1 autoantigen and LJM11 environmental Ag could be the initial antigenic stimulants for the IgG4 autoimmune responses in FS. These results support our hypothesis that LJM11 Ag plays a substantial role in triggering the IgG4 autoantibody development in FS and provide new insights on how noninfectious environmental Ag(s) may drive the generation of autoantibodies in IgG4-related autoimmune diseases. PMID- 26826249 TI - Molecular Basis of the Functional Differences between Soluble Human Versus Murine MD-2: Role of Val135 in Transfer of Lipopolysaccharide from CD14 to MD-2. AB - Myeloid differentiation factor 2 (MD-2) is an extracellular protein, associated with the ectodomain of TLR4, that plays a critical role in the recognition of bacterial LPS. Despite high overall structural and functional similarity, human (h) and murine (m) MD-2 exhibit several species-related differences. hMD-2 is capable of binding LPS in the absence of TLR4, whereas mMD-2 supports LPS responsiveness only when mMD-2 and mTLR4 are coexpressed in the same cell. Previously, charged residues at the edge of the LPS binding pocket have been attributed to this difference. In this study, site-directed mutagenesis was used to explore the hydrophobic residues within the MD-2 binding pocket as the source of functional differences between hMD-2 and mMD-2. Whereas decreased hydrophobicity of residues 61 and 63 in the hMD-2 binding pocket retained the characteristics of wild-type hMD-2, a relatively minor change of valine to alanine at position 135 completely abolished the binding of LPS to the hMD-2 mutant. The mutant, however, retained the LPS binding in complex with TLR4 and also cell activation, resulting in a murine-like phenotype. These results were supported by the molecular dynamics simulation. We propose that the residue at position 135 of MD-2 governs the dynamics of the binding pocket and its ability to accommodate lipid A, which is allosterically affected by bound TLR4. PMID- 26826250 TI - Cutting Edge: Regulatory T Cells Facilitate Cutaneous Wound Healing. AB - Foxp3-expressing regulatory T cells (Tregs) reside in tissues where they control inflammation and mediate tissue-specific functions. The skin of mice and humans contain a large number of Tregs; however, the mechanisms of how these cells function in skin remain largely unknown. In this article, we show that Tregs facilitate cutaneous wound healing. Highly activated Tregs accumulated in skin early after wounding, and specific ablation of these cells resulted in delayed wound re-epithelialization and kinetics of wound closure. Tregs in wounded skin attenuated IFN-gamma production and proinflammatory macrophage accumulation. Upon wounding, Tregs induce expression of the epidermal growth factor receptor (EGFR). Lineage-specific deletion of EGFR in Tregs resulted in reduced Treg accumulation and activation in wounded skin, delayed wound closure, and increased proinflammatory macrophage accumulation. Taken together, our results reveal a novel role for Tregs in facilitating skin wound repair and suggest that they use the EGFR pathway to mediate these effects. PMID- 26826251 TI - Treatment of Uveitis by In Situ Administration of Ex Vivo-Activated Polyclonal Regulatory T Cells. AB - CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cell therapy is a promising approach for the treatment of autoimmune diseases. To be effective, Treg cells should be in an activated state in the target tissue. This can be achieved by systemic administration of Ag-specific Treg cells, which are difficult to produce in conditions that can be translated to the clinic. In this paper, we propose an alternative approach consisting of in situ injection of preactivated polyclonal Treg cells that would exert bystander suppression in the target tissue. We show that polyclonal Treg cells suppressed uveitis in mice as efficiently as Ag specific Treg cells but only when preactivated and administered in the vitreous. Uveitis control was correlated with an increase of IL-10 and a decrease of reactive oxygen species produced by immune cell infiltrates in the eye. Thus, our results reveal a new mechanism of Treg cell-mediated suppression and a new Treg cell therapy approach. PMID- 26826254 TI - Visual Illusions Based on Processes: New Classification System Needed. AB - Illusions have mainly been classified according to their phenomenological appearance. Here, I plead for a new classification approach based on processing areas or mechanisms. Classifying visual illusions according to processing areas or mechanisms may not only be valuable for a better understanding of the visual system but also for diagnostics of impairments, degenerative effects, and lesions (from retina to striate and extra-striate cortex). PMID- 26826252 TI - A Context-Dependent Role for IL-21 in Modulating the Differentiation, Distribution, and Abundance of Effector and Memory CD8 T Cell Subsets. AB - The activation of naive CD8 T cells typically results in the formation of effector cells (TE) as well as phenotypically distinct memory cells that are retained over time. Memory CD8 T cells can be further subdivided into central memory, effector memory (TEM), and tissue-resident memory (TRM) subsets, which cooperate to confer immunological protection. Using mixed bone marrow chimeras and adoptive transfer studies in which CD8 T cells either do or do not express IL 21R, we discovered that under homeostatic or lymphopenic conditions IL-21 acts directly on CD8 T cells to favor the accumulation of TE/TEM populations. The inability to perceive IL-21 signals under competitive conditions also resulted in lower levels of TRM phenotype cells and reduced expression of granzyme B in the small intestine. IL-21 differentially promoted the expression of the chemokine receptor CX3CR1 and the integrin alpha4beta7 on CD8 T cells primed in vitro and on circulating CD8 T cells in the mixed bone marrow chimeras. The requirement for IL-21 to establish CD8 TE/TEM and TRM subsets was overcome by acute lymphocytic choriomeningitis virus infection; nevertheless, memory virus-specific CD8 T cells remained dependent on IL-21 for optimal accumulation in lymphopenic environments. Overall, this study reveals a context-dependent role for IL-21 in sustaining effector phenotype CD8 T cells and influencing their migratory properties, accumulation, and functions. PMID- 26826255 TI - A Note on the Horizontal--Vertical Illusion - A Reply to Wade (2014). AB - Like many others before him, Nicholas Wade, in a recent publication in this journal, did not provide the correct title of Adolf Fick's dissertation, approved by the University at Marburg, Germany, in 1851, and Wade also wrongly attributed now famous illusion figures, meant to illustrate the so-called horizontal vertical illusion (the +, the L, and the inverted T), to this author. After having corrected these errors, I briefly relate Fick's work to modern work in the field and note that it has been widely neglected. PMID- 26826256 TI - Using Japanese Onomatopoeias to Explore Perceptual Dimensions in Visual Material Perception. AB - This study examined the perceptual dimensions of visual material properties. Photographs of 50 objects were presented to the participants, and they reported a suitable onomatopoeia (mimetic word) for describing the material of the object in each photograph, based on visual appearance. The participants' responses were collated into a contingency table of photographs * onomatopoeias. After removing some items from the table, correspondence analysis was applied to the contingency table, and a six-dimensional biplot was obtained. By rotating the axes to maximize sparseness of the coordinates for the items in the biplot, three meaningful perceptual dimensions were derived: wetness/stickiness, fluffiness/softness, and smoothness-roughness/gloss-dullness. Two additional possible dimensions were obtained: crumbliness and coldness. These dimensions, except gloss-dullness, were paid little attention to in vision science, though they were suggested as perceptual dimensions of tactile texture. This suggests that the perceptual dimensions that are considered to be primarily related to haptics are also important in visual material perception. PMID- 26826253 TI - What's new in estrogen receptor action in the female reproductive tract. AB - Estrogen receptor alpha (ERalpha) is a critical player in development and function of the female reproductive system. Perturbations in ERalpha response can affect wide-ranging aspects of health in humans as well as in livestock and wildlife. Because of its long-known and broad impact, ERalpha mechanisms of action continue to be the focus on cutting-edge research efforts. Consequently, novel insights have greatly advanced understanding of every aspect of estrogen signaling. In this review, we attempt to briefly outline the current understanding of ERalpha mediated mechanisms in the context of the female reproductive system. PMID- 26826257 TI - Big Money: The Effect of Money Size on Value Perceptions and Saving Motivation. AB - Motivated perception has been shown to affect people's estimates of money (e.g., perceiving coins as larger than real size). In the present research, we examine whether simply varying the size of a picture of money can affect its perceived value and subsequent decisions. Participants presented with a picture of money enlarged by 15% perceived the depicted money as more valuable compared with those seeing a real-size picture (Study 1). When told to imagine their own cash and banked money in the depicted form, participants presented with a picture enlarged by 15% felt more subjectively wealthy and reported fewer intentions to conserve their money compared with those seeing a real-size picture of the same money (Study 2). Together, these studies suggest that judgments about money and even attitudes toward personal spending can be influenced by manipulating the size of a picture of money. PMID- 26826258 TI - Mixture of Arginine, Glutamine, and beta-hydroxy-beta-methyl Butyrate Enhances the Healing of Ischemic Wounds in Rats. AB - BACKGROUND: This study investigated the effects of an amino acid mixture containing arginine, glutamine, and beta-hydroxy-beta-methyl butyrate on secondary healing of ischemic wounds in a rat model (N = 18). METHODS: After the formation of a bipediculated flap on each rat, 2 full-thickness excisional skin wounds (2 * 2 cm) were created on every flap. The rats were then randomized into the control and treatment groups. Every rat received standardized rat food throughout the study. The rats in the treatment group were administered an extra 200 mg/kg of L-arginine, 200 mg/kg of L-glutamine, and 40 mg/kg of beta-hydroxy beta-methyl butyrate per day. Wound sizes were measured on days 0, 4, 10, and 14. The rats were sacrificed, and the wounds were excised for biochemical and histologic examination on the 14th day. RESULTS: As compared with the control group, the treatment group's wound sizes were significantly smaller on days 10 and 14 ( P < .001), as was its inflammatory cell accumulation score ( P = .008). There was no significant difference between the 2 groups in collagen accumulation ( P = .340), granulation tissue maturation ( P = .161), angiogenesis ( P = .387), or reepithelialization ( P = .190) and no significant difference between hydroxyproline concentrations in wounds ( P = .287). DISCUSSION: This amino acid combination seems to have a positive impact on the secondary healing of experimental ischemic wounds when introduced as a supplement to the standard diet, and the reduction in the inflammatory process appears to play a role in this effect. PMID- 26826259 TI - Exploring and Enhancing the Anti-Inflammatory Properties of Polymeric Formula. AB - BACKGROUND: Exclusive enteral nutrition (EEN) therapy using a polymeric formula (PF) can substantially attenuate intestinal inflammation in Crohn's disease (CD) patients. However, the mechanism(s) by which EEN suppresses inflammation are not yet fully understood. The aims were to examine cellular mechanism(s) through which EEN may suppress inflammation and investigate potential pathways to enhance anti-inflammatory properties of EEN. METHODS: Glutamine, arginine, vitamin D3, and alpha linolenic acid (ALA), present in PF, along with curcumin, were identified as immunoactive nutrient therapies. Tumor necrosis factor (TNF)-alpha exposed HT-29 colonic epithelial cells were used to investigate the immunosuppressive activity of the nutrients by assessing their effect on cell viability, cell activity, chemokine response (interleukin-8 [IL-8]), nuclear factor (NF)-kappaB, P38 mitogen-activated protein kinase, IkappaB kinase (Ikappakappa), and nitric oxide (NO). RESULTS: Cellular viability and activity were maintained with all nutrient treatments. Glutamine, arginine, and vitamin D3, but not ALA, significantly attenuated IL-8 production. Glutamine and arginine led to phosphorylation blockade of the signaling components in NF-kappaB and P38 pathways, reduction in kinase activity, and enhancement in NO production. Combining glutamine, arginine, and curcumin at optimal concentrations completely abolished the IL-8 response. CONCLUSIONS: These data indicate that glutamine, arginine, and vitamin D3 can suppress inflammation at concentrations equivalent to those used in PF. The mechanisms of this action were mediated through influencing the NF-kappaB and P38 cascades. Glutamine and arginine-fortified PF with curcumin might be a promising option to enhance the effectiveness and expand the scope of EEN therapy in CD treatment. PMID- 26826260 TI - Use of a Loading Dose of Vitamin D for Treatment of Vitamin D Deficiency in Patients With Intestinal Failure. AB - Vitamin D deficiency is common in patients with intestinal failure and short bowel syndrome who have been weaned of parenteral nutrition. Dietary supplementation with vitamin D is necessary to correct this deficiency. In certain cases, routine supplementation strategy may be ineffective. We report 3 cases of vitamin D deficiency in patients with intestinal failure who showed improvement in serum 25-hydroxyvitamin D levels after supplementation with a loading dose of 20,000-40,000 IU vitamin D provided weekly. PMID- 26826261 TI - Effects of Ethanol Lock Therapy on Central Line Infections and Mechanical Problems in Children With Intestinal Failure. AB - OBJECTIVES: Although use of 70% ethanol lock therapy (ELT) has been shown to decrease the rate of catheter-related bloodstream infections (CRBSIs) in patients with intestinal failure and central venous catheters (CVCs), concerns have been raised about its association with higher rates of mechanical problems and CVC replacements (CVC-Rs). We sought to compare the rates of CRBSI, mechanical problems, and CVC-Rs in a cohort of pediatric patients with intestinal failure, with and without ELT (ELT+ and ELT-, respectively). METHODS: Data were collected in a retrospective chart review from February 2007 to May 2014. Mann-Whitney and Wilcoxon signed-rank tests were used to compare nonparametric and paired data, respectively. RESULTS: Twenty-nine children had 9033 catheter days (CDs). The ELT+ group (vs ELT-) had lower rate of infection and significantly fewer CVC-Rs due to infection but significantly more mechanical events and related CVC-Rs with significantly shorter mean CVC survival. In 13 children who had a pre-ELT and post-ELT period, ELT was associated with a decrease in the rate of CVC-Rs due to infection (0.36 vs 4.74/1000 CDs, P = .046) and an increase in the rate of CVC-Rs due to mechanical problems (5.05 vs 0/1000 CDs, P = .018). CONCLUSIONS: While ELT+ is associated with a lower rate of CRBSIs and related CVC-Rs, it is also associated with higher rates of mechanical problems and related CVC-Rs. In addition to investigating the ideal concentration, duration, and timing of ELT to preserve the integrity of the CVC, alternatives to exclusively ethanol-based lock solutions should be developed. PMID- 26826262 TI - Energy Expenditure in Critically Ill Elderly Patients: Indirect Calorimetry vs Predictive Equations. AB - BACKGROUND: Predictive equations (PEs) are used for estimating resting energy expenditure (REE) when the measurements obtained from indirect calorimetry (IC) are not available. This study evaluated the degree of agreement and the accuracy between the REE measured by IC (REE-IC) and REE estimated by PE (REE-PE) in mechanically ventilated elderly patients admitted to the intensive care unit (ICU). METHODS: REE-IC of 97 critically ill elderly patients was compared with REE-PE by 6 PEs: Harris and Benedict (HB) multiplied by the correction factor of 1.2; European Society for Clinical Nutrition and Metabolism (ESPEN) using the minimum (ESPENmi), average (ESPENme), and maximum (ESPENma) values; Mifflin-St Jeor; Ireton-Jones (IJ); Fredrix; and Luhrmann. Degree of agreement between REE PE and REE-IC was analyzed by the interclass correlation coefficient and the Bland-Altman test. The accuracy was calculated by the percentage of male and/or female patients whose REE-PE values differ by up to +/-10% in relation to REE-IC. RESULTS: For both sexes, there was no difference for average REE-IC in kcal/kg when the values obtained with REE-PE by corrected HB and ESPENme were compared. A high level of agreement was demonstrated by corrected HB for both sexes, with greater accuracy for women. The best accuracy in the male group was obtained with the IJ equation but with a low level of agreement. CONCLUSIONS: The effectiveness of PEs is limited for estimating REE of critically ill elderly patients. Nonetheless, HB multiplied by a correction factor of 1.2 can be used until a specific PE for this group of patients is developed. PMID- 26826264 TI - Utility of Aminotransferase/Platelet Ratio Index to Predict Liver Fibrosis in Intestinal Failure-Associated Liver Disease in Pediatric Patients. AB - BACKGROUND: Intestinal failure-associated liver disease (IFALD) is a frequent indication for intestinal transplantation. Liver biopsy (LBX) is the gold standard test for its diagnosis. Identifying noninvasive markers of fibrosis progression would be of considerable clinical use. Aspartate aminotransferase/platelet ratio index (APRI) has a good correlation in adult patients with chronic liver disease; few studies have been performed in children with IFALD. AIM: To evaluate APRI in a cohort of children with IFALD. MATERIALS AND METHODS: Retrospective analysis of a prospective database of patients <18 years with severe intestinal failure and at least 1 LBX, registered in our unit from March 2006 to December 2014. RESULTS: Forty-nine LBX were done on 36 patients: 20 were male, and 31 had short gut. Fibrosis was found in 71% of LBX. Biopsies were grouped according to the fibrosis stage (METAVIR [M]): (1) group 1 (G1) LBX with M 0, 1, 2 (n = 33) and (2) group 2 (G2) LBX with M 3, 4 (n = 16). The median APRI score was 0.92 (interquartile range [IQR] 0.63-1.50) for G1 and 2.50 (IQR 1.81-5.82) for G2 ( P = .001) The c statistic of the receiving operating characteristic curve was 0.79 (95% CI 0.64-0.94; P < .001). The analyses allowed identifying a cutoff value for APRI of 1.6 as the point with the best sensitivity (81%) and specificity (76%) to predict advanced fibrosis. CONCLUSIONS: APRI in this cohort of patients shows that a score >1.6 correlates with advanced fibrosis. PMID- 26826263 TI - Improved Glucose Profile in Patients With Type 2 Diabetes With a New, High Protein, Diabetes-Specific Tube Feed During 4 Hours of Continuous Feeding. AB - BACKGROUND: Hyperglycemia frequently occurs in hospitalized patients receiving nutrition support. In this study, the effects of a new diabetes-specific formula (DSF) on glucose profile during 4 hours of continuous feeding and 4 hours after stopping feeding were compared with a standard formula (SF). MATERIALS AND METHODS: In this randomized, controlled, double-blind, crossover study, ambulant, nonhospitalized patients with type 2 diabetes received the DSF or an isocaloric, fiber-containing SF via a nasogastric tube. After overnight fasting, the formula was continuously administered to the patients during 4 hours. Plasma glucose and insulin concentrations were determined during the 4-hour period and in the subsequent 4 hours during which no formula was provided. RESULTS: During the 4 hour feeding period, DSF compared with SF resulted in a lower mean delta glucose concentration in the 3- to 4-hour period (0.3 +/- 1.0 and 2.4 +/- 1.5 mmol/L; P < .001). Also, the (delta) peak concentrations, (delta) mean concentrations, and incremental area under the curve (iAUC) for glucose and insulin were significantly lower during DSF compared with SF feeding (all comparisons: P < .001). Furthermore, fewer patients experienced hyperglycemia (>10 mmol/L) on DSF compared with SF (2 vs 11, P = .003, respectively). No differences in number of patients with hypoglycemia (<3.9 mmol/L) were observed. No significant differences in tolerance were observed. CONCLUSION: Administration of a new, high protein DSF during 4 hours of continuous feeding resulted in lower glucose and insulin levels compared with a fiber-containing SF in ambulant, nonhospitalized patients with type 2 diabetes. These data suggest that a DSF may contribute to lower glucose levels in these patients. PMID- 26826265 TI - Transient neurologic event following administration of foam sclerotherapy. AB - This report describes a complication of symptoms consistent with transient ischemic attack following administration of physician-compounded foam sclerotherapy created with room air. After intravenous administration of 8 cc of foam sclerosant prepared with room air and polidocanol using the Tessari method, an otherwise healthy man experienced transient neurologic changes. Immediately following injection of foam, a dense hemiplegia consistent with interruption of the middle cerebral arterial circulation was observed. The patient's symptoms resolved completely over approximately 30 min with interventions including Trendelenburg positioning and supplemental oxygen via nasal cannula. PCP foam sclerotherapy with room air administered in typical concentrations, preparations, and volumes may result in severe neurologic events in otherwise healthy individuals. Continued investigation into the potential role of product, gas, volume and technique to identify optimal approaches may further refine the consistency and safety of foam sclerotherapy. PMID- 26826266 TI - The sural nerve: Sonographic anatomy, variability and relation to the small saphenous vein in the setting of endovenous thermal ablation. AB - Background Neurological complications are well documented in association with both surgical stripping or disconnection and thermal ablation of the small saphenous vein. The sural nerve (medial sural cutaneous nerve) is most vulnerable due to its close relationship to the small saphenous vein. Objective This is a cross-sectional observational study of the sonographic anatomy of 115 Australian patients to determine the course of the sural nerve and its relationship to the small saphenous vein, and to identify its relevance in the thermal ablation of the small saphenous vein. Method Sonographic mapping of the right sural nerve was performed with a Philips L12.5 and Sonosite 10.5 MHz ultrasound machine on 115 patients. The sural nerve was traced proximally from the level of the lateral malleolus to the popliteal fossa in order to measure its distance from the small saphenous vein at four reference points in the lower leg. Results A total of 115 patients were studied (females 82, males 33). The sural nerve was identified in 100% of patients; 64 patients (55.7%) showed usual sural nerve anatomy, while 51 patients (44.3%) demonstrated a range of anatomical variations, including the sural nerve becoming epifascial at a higher point than usual. Conclusion The sural nerve was identifiable on duplex ultrasound in 100% of cases. Classic anatomical relations and the perceived protection of the sural nerve conferred by the deep fascia of the upper calf are unreliable. Preoperative strategies can help to approach and protect the sural nerve in the endovenous ablation setting. PMID- 26826267 TI - Antiproliferative effect and apoptotic activity of linear geranylphenol derivatives from phloroglucinol and orcinol. AB - Sixteen synthetic linear derivatives geranylphenols, were obtained from phloroglucinol and orcinol, and cytotoxic activity was evaluated in vitro against cancer cell lines (HT-29, PC-3, MDA-MB231, DU-145) and one non-tumor cell line, human dermal fibroblast (HDF). IC50 values were determined at concentrations of 0 100 MUM of each compound for 72 h. Compounds 12, 13, 17, 21, 22 and 25, showed cytotoxic activity. To elucidate whether these compounds reduce cell viability by inducing apoptosis, cell lines MCF-7, PC-3 and DHF were treated with each active compound 12, 13, 17, 21, 22 and 25 and were examined after Hoechst 33342 staining. The compounds 12, 13 and 17 induced apoptosis in various cancer cell lines, as shown by nuclear condensation and/or fragmentation. In addition, it was found that compounds 12 and 13, induced changes in mitochondrial membrane permeability in those cancer cell lines. Such induction was associated with the depletion of mitochondrial membrane potential. These activities led to the cleavage of caspases inducing the cell death process. PMID- 26826268 TI - Three kinds of Ganoderma lucidum polysaccharides attenuate DDC-induced chronic pancreatitis in mice. AB - Chronic pancreatitis (CP) is a progressive inflammation of pancreas characterized by irreversible morphologic change and dysfunction. Patients with chronic pancreatitis often present with abdominal pain, diarrhoea, jaundice, weight loss and the development of diabetes. Polysaccharides of Ganoderma lucidum strain S3 (GLPS3) possess antioxidative and immunomodulatory activities. This study was to characterize chemical structures of GLPS3 and determine their effects on diethyldithiocarbamate (DDC)-induced CP in mice. The total sugar content of GLPS3 from fermentation broth (GLPS3-I), cultured mycelia (GLPS3-II) and fruiting body (GLPS3-III) was 90.4%, 92.2% and 91.8% respectively. GLPS3-I, GLPS3-II and GLPS3 III were composed of Glu:Gal:Ara:Xyl, Glu:Gal:Ara:Xyl:Man:Rha, and Glu:Gal:Xyl:Man:Rha:Fuc, with molar ratio of 2.82: 1.33: 1.26: 0.87, 5.84: 2.23: 0.72:1.38: 1.40: 0.51 and 5.34: 2.72: 1.14: 1.10: 0.33: 0.38, respectively. The antioxidative activity of GLPS3-IIfrom cultured mycelia in vitro is higher than other two polysaccharides. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum were increased while the malondialdehyde (MDA) levels were reversely decreased by GLPS3 treatment. Serum amylase (AMS) and lactic dehydrogenase (LDH) changes indicated the therapeutic effects of GLPS3. Moreover, interleukin-1beta (IL-1beta) and interferon-gamma (INF-gamma) contents were reduced most by GLPS3-II. The results revealed that GLPS3 especially GLPS3 IIfrom cultured mycelia were effective for CP therapy and bioactivity difference might be attributed to monosaccharide composition. PMID- 26826270 TI - Living on the edge: Simulations of bacterial outer-membrane proteins. AB - Gram-negative bacteria are distinguished in part by a second, outer membrane surrounding them. This membrane is distinct from others, possessing an outer leaflet composed not of typical phospholipids but rather large, highly charged molecules known as lipopolysaccharides. Therefore, modeling the structure and dynamics of proteins embedded in the outer membrane requires careful consideration of their native environment. In this review, we examine how simulations of such outer-membrane proteins have evolved over the last two decades, culminating most recently in detailed, highly accurate atomistic models of the outer membrane. We also draw attention to how the simulations have coupled with experiments to produce novel insights unattainable through a single approach. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. PMID- 26826269 TI - Copper delivery to the CNS by CuATSM effectively treats motor neuron disease in SOD(G93A) mice co-expressing the Copper-Chaperone-for-SOD. AB - Over-expression of mutant copper, zinc superoxide dismutase (SOD) in mice induces ALS and has become the most widely used model of neurodegeneration. However, no pharmaceutical agent in 20 years has extended lifespan by more than a few weeks. The Copper-Chaperone-for-SOD (CCS) protein completes the maturation of SOD by inserting copper, but paradoxically human CCS causes mice co-expressing mutant SOD to die within two weeks of birth. Hypothesizing that co-expression of CCS created copper deficiency in spinal cord, we treated these pups with the PET imaging agent CuATSM, which is known to deliver copper into the CNS within minutes. CuATSM prevented the early mortality of CCSxSOD mice, while markedly increasing Cu, Zn SOD protein in their ventral spinal cord. Remarkably, continued treatment with CuATSM extended the survival of these mice by an average of 18 months. When CuATSM treatment was stopped, these mice developed ALS-related symptoms and died within 3 months. Restoring CuATSM treatment could rescue these mice after they became symptomatic, providing a means to start and stop disease progression. All ALS patients also express human CCS, raising the hope that familial SOD ALS patients could respond to CuATSM treatment similarly to the CCSxSOD mice. PMID- 26826271 TI - Identification of protein-protein interactions between the TatB and TatC subunits of the twin-arginine translocase system and respiratory enzyme specific chaperones. AB - The Twin-arginine translocation (Tat) pathway serves for translocation of fully folded proteins across the cytoplasmic membrane in bacterial and chloroplast thylakoid membranes. The Escherichia coli Tat system consists of three core components: TatA, TatB, and TatC. The TatB and TatC subunits form the receptor complex for Tat dependent proteins. The TatB protein is composed of a single transmembrane helix and cytoplasmic domain. The structure of TatC revealed six transmembrane helices. Redox Enzyme Maturation Proteins (REMPs) are system specific chaperones, which play roles in the maturation of Tat dependent respiratory enzymes. Here we applied the in vivo bacterial two-hybrid technique to investigate interaction of REMPs with the TatBC proteins, finding that all but the formate dehydrogenase REMP dock to TatB or TatC. We focused on the NarJ subfamily, where DmsD--the REMP for dimethyl sulfoxide reductase in E. coli--was previously shown to interact with TatB and TatC. We found that these REMPs interact with TatC cytoplasmic loops 1, 2 and 4, with the exception of NarJ, that only interacts with 1 and 4. An in vitro isothermal titration calorimetry study was applied to confirm the evidence of interactions between TatC fragments and DmsD chaperone. Using a peptide overlapping array, it was shown that the different NarJ subfamily REMPs interact with different regions of the TatB cytoplasmic domains. The results demonstrate a role of REMP chaperones in targeting respiratory enzymes to the Tat system. The data suggests that the different REMPs may have different mechanisms for this task. PMID- 26826272 TI - Non-Brownian diffusion in lipid membranes: Experiments and simulations. AB - The dynamics of constituents and the surface response of cellular membranes-also in connection to the binding of various particles and macromolecules to the membrane-are still a matter of controversy in the membrane biophysics community, particularly with respect to crowded membranes of living biological cells. We here put into perspective recent single particle tracking experiments in the plasma membranes of living cells and supercomputing studies of lipid bilayer model membranes with and without protein crowding. Special emphasis is put on the observation of anomalous, non-Brownian diffusion of both lipid molecules and proteins embedded in the lipid bilayer. While single component, pure lipid bilayers in simulations exhibit only transient anomalous diffusion of lipid molecules on nanosecond time scales, the persistence of anomalous diffusion becomes significantly longer ranged on the addition of disorder-through the addition of cholesterol or proteins-and on passing of the membrane lipids to the gel phase. Concurrently, experiments demonstrate the anomalous diffusion of membrane embedded proteins up to macroscopic time scales in the minute time range. Particular emphasis will be put on the physical character of the anomalous diffusion, in particular, the occurrence of ageing observed in the experiments the effective diffusivity of the measured particles is a decreasing function of time. Moreover, we present results for the time dependent local scaling exponent of the mean squared displacement of the monitored particles. Recent results finding deviations from the commonly assumed Gaussian diffusion patterns in protein crowded membranes are reported. The properties of the displacement autocorrelation function of the lipid molecules are discussed in the light of their appropriate physical anomalous diffusion models, both for non-crowded and crowded membranes. In the last part of this review we address the upcoming field of membrane distortion by elongated membrane-binding particles. We discuss how membrane compartmentalisation and the particle-membrane binding energy may impact the dynamics and response of lipid membranes. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Rog. PMID- 26826273 TI - Regimen of ovarian stimulation affects oocyte and therefore embryo quality. AB - Without any doubt the regimen used to mature multiple capable oocytes for IVF impacts IVF outcomes. Studies have indicated that the inclusion of LH activity, adjuvant agents such as growth hormone (GH), and regimens providing for simultaneous action of both LH and FSH during final oocyte maturation may have beneficial effects on IVF outcomes. Because of the difficulty in improving IVF outcomes in poor responders, the studies on GH are of particular interest. As pointed out in this review, the apparent beneficial effects of GH on oocyte competence may also apply to older women or to normal responders with reduced embryo quality. A much more difficult question is whether and how much ovarian stimulation impacts on oocyte competence. Paradoxically it seems that there are not demonstrated differences between the stimulated and the natural unstimulated cycle, whereas studies in laboratory animals and IVF patients have shown deleterious effects of higher compared with lower doses of gonadotropins. Recent studies suggest that the use of high doses of gonadotropins as an independent factor correlates negatively with the probability of live birth, whereas a high ovarian response per se is associated with better cumulative pregnancy rates, owing to the availability of more euploid and good-quality embryos. Although adjunctive use of androgens has not been discussed here, it is briefly covered in the first review of this series. PMID- 26826274 TI - Sequential versus Monophasic Media Impact Trial (SuMMIT): a paired randomized controlled trial comparing a sequential media system to a monophasic medium. AB - OBJECTIVE: To determine whether sequential or monophasic media is the more optimal formulation for blastocyst development and sustained implantation rates (SIR) in IVF. DESIGN: Paired randomized controlled trials. SETTING: Academic. PATIENT(S): Infertile couples (N = 192) with female partner <=42 years old and normal ovarian reserve. INTERVENTION(S): Fertilized zygotes from each patient were randomly divided into two groups: [1] cultured in sequential media and [2] cultured in monophasic medium. Sequential media consisted of Quinn's Advantage Cleavage Medium (SAGE) followed by Blast Assist (Origio). The monophasic medium used was Continuous Single Culture (Irvine Scientific). Paired ETs were accomplished by transferring the best euploid blastocyst from each media group. DNA fingerprinting was used to link outcomes. MAIN OUTCOME MEASURE(S): The primary outcome measure was the proportion of blastocysts suitable for clinical use. Secondary outcome measures included timing of blastulation, aneuploidy rates, and SIR. Sustained implantation rate is defined as the number fetal heart beats at 8-9 weeks of gestation, divided by the number of embryos transferred. RESULT(S): A total of 192 patients had their 2PN embryos (N = 2,257) randomized to each culture system. Sequential media had higher blastulation rate than monophasic medium (55.2% vs. 46.9%). No differences were found in the day of blastulation or aneuploidy rate. Of the 168 patients who had euploid blastocysts suitable for transfer, 126 completed a paired ET. Among the double ETs, there was no difference in implantation between groups. CONCLUSION(S): This is the first randomized controlled trial to examine paired euploid transfers of sibling zygotes cultured in sequential versus monophasic media. This study demonstrates that the usable blastocyst rate is greatest after culture in the sequential media tested in comparison with the monophasic formulation selected for study. However, no difference exists in timing of blastulation, aneuploidy, or SIR. Whether these observations are generalizable to other media systems remains to be determined. CLINICAL TRIAL REGISTRATION NUMBER: NCT01917240. PMID- 26826275 TI - Access to and use of infertility services in the United States: framing the challenges. AB - An overview of access to and use of general infertility and assisted reproductive technology (ART) services in the United States (U.S.) shows a declining trend for the ever-use of infertility services. Moreover, the use of ART services lags relative to other member nations of the Organization for Economic Co-operation and Development (OECD). Access to and use of general infertility and ART services is primarily undermined by a severely constrained underwriting universe dominated by self-insured employers and by a finite number of state infertility insurance mandates. The contribution of traditional public and private payers to the underwriting of ART is limited. As compared with OECD member nations wherein the access to and underwriting of general infertility and ART services is universal, the current status quo in the U.S. can only be characterized as dismal. Further, the current state of affairs is socially unjust in that the right to build a family in the face of infertility appears to have become a function of economic prowess. Given the dominance of the self-insured employers as underwriters of general infertility and ART services, advocacy directed at this interest group is likely to prove most productive. Improving the state of underwriting of general infertility and ART services in the U.S. must be embraced as a central moral imperative and as an unwavering strategic goal of the professional societies entrusted with the reproductive health of women and men. PMID- 26826276 TI - The choice of phorbol 12-myristate 13-acetate differentiation protocol influences the response of THP-1 macrophages to a pro-inflammatory stimulus. AB - The human monocytic cell line, THP-1, is the most widely used model for primary human monocytes/macrophages. This is because, following differentiation using phorbol 12-myristate 13-acetate (PMA), THP-1 cells acquire a macrophage-like phenotype, which mimics, in many respects, primary human macrophages. Despite the widespread use of THP-1 cells in studies elucidating macrophage responses to inflammatory stimuli, as well as the development and screening of potential therapeutics, there is currently no standardised protocol for the reliable differentiation of THP-1 monocytes to a macrophage phenotype using PMA. Consequently, reports using THP-1 cells have demonstrated significant phenotypic and functional differences between resultant THP-1 macrophage populations, which are largely attributable to the varying PMA differentiation methods used. Thus, to guarantee consistency and reproducibility between studies, and to ensure the relevance of THP-1 cells as an appropriate model for primary human macrophages, it is crucial to develop a standardised protocol for the differentiation of THP-1 macrophages. Accordingly, we compared the function and phenotype of THP-1 macrophages generated using the range of published PMA differentiation protocols, specifically in response to the pro-inflammatory stimulus, lipopolysaccharide (LPS). Our results demonstrated that the function of the resultant THP-1 macrophage populations, as determined by tumour necrosis factor (TNF) secretion in response to LPS stimulation, varied significantly, and was dependent upon the concentration of PMA used to stimulate the differentiation of monocytes, and the period of rest following PMA exposure. These data indicate that exposure of monocytic THP-1 cells to 25 nM PMA over 48 h, followed by a recovery period of 24h in culture in the absence of PMA, was the optimal protocol for the differentiation of THP-1 cells. PMID- 26826277 TI - T-cell libraries allow simple parallel generation of multiple peptide-specific human T-cell clones. AB - Isolation of peptide-specific T-cell clones is highly desirable for determining the role of T-cells in human disease, as well as for the development of therapies and diagnostics. However, generation of monoclonal T-cells with the required specificity is challenging and time-consuming. Here we describe a library-based strategy for the simple parallel detection and isolation of multiple peptide specific human T-cell clones from CD8(+) or CD4(+) polyclonal T-cell populations. T-cells were first amplified by CD3/CD28 microbeads in a 96U-well library format, prior to screening for desired peptide recognition. T-cells from peptide-reactive wells were then subjected to cytokine-mediated enrichment followed by single-cell cloning, with the entire process from sample to validated clone taking as little as 6 weeks. Overall, T-cell libraries represent an efficient and relatively rapid tool for the generation of peptide-specific T-cell clones, with applications shown here in infectious disease (Epstein-Barr virus, influenza A, and Ebola virus), autoimmunity (type 1 diabetes) and cancer. PMID- 26826278 TI - Development of a novel multiplex electrochemiluminescent-based immunoassay for quantification of human serum IgG against 10 Staphylococcus aureus toxins. AB - An electrochemiluminescent (ECL)-based multiplex immunoassay using Meso-Scale Discovery (MSD) technology was developed for detecting antibody response toward 10 Staphylococcus aureus (S. aureus) exotoxins. These 10 antigens included three different groups of toxins: 1) single component pore-forming toxins such as alpha and delta-hemolysins, 2) the bicomponent pore-forming toxin Panton-Valentine leukocidin (PVL), comprised of LukS-PV and LukF-PV subunits, and 3) enterotoxin/superantigens - Staphylococcal enterotoxins A (SEA), B (SEB), C1 (SEC1), D (SED), K (SEK) and Toxic shock syndrome toxin-1 (TSST-1). Assay development included optimization steps with a conventional SEB ELISA-based serological assay and then optimized parameters were transferred and re-optimized in a singleplex ECL format. Finally, two pentaplex solid-phase ECL formats were developed. As proof of concept, one set of pentaplex ECL data was compared with conventional ELISA results. During the assay development controls were screened and developed for both the singleplex and multiplex assays. ECL-based multiplex assays were more sensitive with a wide dynamic range and proved more time efficient than conventional ELISAs. Using the newly developed ECL method we showed, for the first time, that delta-hemolysin toxin can induce an immune response as antibody titers could be detected. PMID- 26826279 TI - From preclinical development to clinical application: Kit formulation for radiolabelling the minigastrin analogue CP04 with In-111 for a first-in-human clinical trial. AB - INTRODUCTION: A variety of radiolabelled minigastrin analogues targeting the cholecystokinin 2 (CCK2) receptor were developed and compared in a concerted preclinical testing to select the most promising radiotracer for diagnosis and treatment of medullary thyroid carcinoma (MTC). DOTA-DGlu-DGlu-DGlu-DGlu-DGlu DGlu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 (CP04) after labelling with (111)In displayed excellent characteristics, such as high stability, receptor affinity, specific and persistent tumour uptake and low kidney retention in animal models. Therefore, it was selected for further clinical evaluation within the ERA-NET project GRAN-T-MTC. Here we report on the development of a pharmaceutical freeze dried formulation of the precursor CP04 for a first multi-centre clinical trial with (111)In-CP04 in MTC patients. MATERIALS AND METHODS: The kit formulation was optimised by adjustment of buffer, additives and radiolabelling conditions. Three clinical grade batches of a final kit formulation with two different amounts of peptide (10 or 50 MUg) were prepared and radiolabelled with (111)In. Quality control and stability assays of both the kits and the resulting radiolabelled compound were performed by HPLC analysis. RESULTS: Use of ascorbic acid buffer (pH4.5) allowed freeze-drying of the kit formulation with satisfactory pellet formation. Addition of methionine and gentisic acid as well as careful selection of radiolabelling temperature was required to avoid extensive oxidation of the Met(11)-residue. Trace metal contamination, in particular Zn, was found to be a major challenge during the pharmaceutical filling process in particular for the 10 MUg formulation. The final formulations contained 10 or 50 MUg CP04, 25mg ascorbic acid, 0.5mg gentisic acid and 5mg L-methionine. The radiolabelling performed by incubation of 200-250 MBq (111)InCl3 at 90 degrees C for 15 min resulted in reproducible radiochemical purity (RCP) >94%. Kit-stability was proven for >6 months at +5 degrees C and at +25 degrees C. The radiolabelled product was stable for >4h at +25 degrees C. CONCLUSION: A kit formulation to prepare (111)In-CP04 for clinical application was developed, showing high stability of the kit as well as high RCP of the final product. PMID- 26826280 TI - Influence of PVP/VA copolymer composition on drug-polymer solubility. AB - In this study, the influence of copolymer composition on drug-polymer solubility was investigated. The solubility of the model drug celecoxib (CCX) in various polyvinylpyrrolidone/vinyl acetate (PVP/VA) copolymer compositions (70/30, 60/40, 50/50 and 30/70 w/w) and the pure homopolymers polyvinylpyrrolidone (PVP) and polyvinyl acetate (PVA) was predicted at 25 degrees C using a thermal analysis method based on the recrystallization of a supersaturated amorphous dispersion (recrystallization method). These solubilities were compared with a prediction based on the solubility of CCX in the liquid monomeric precursors of PVP/VA, N vinylpyrrolidone (NVP) and vinyl acetate (VA), using the Flory-Huggins lattice theory (liquid monomer solubility approach). The solubilities predicted from the liquid monomer solubility approach increased linearly with increasing VP/VA ratio from 0.03-0.60 w/w. Even though the solubilities predicted from the recrystallization method also increased with increasing VP/VA ratio from 0.02 0.40 w/w, the predicted solubility seemed to approach a plateau at high VP/VA ratios. Increasing positive deviations from the Gordon-Taylor equation with increasing VP/VA ratio indicated strong interactions between CCX and the VP repeat unit, which was in accordance with the relatively high solubilities predicted using both methods. As the solubility plateau may be a consequence of steric hindrance caused by the size differences between CCX and the VP repeat units, it is likely that a CCX molecule interacting with a VP repeat unit hinders another CCX molecule from binding to the neighboring repeat units in the polymer chain. Therefore, it is possible that replacing these neighboring hygroscopic VP repeat units with hydrophobic VA repeat units, could increase the physical stability of an amorphous solid dispersion without compromising the drug-polymer solubility. This knowledge could be used advantageously in future development of amorphous drug delivery systems as copolymers could be customized to provide optimal drug-polymer solubility and physical stability. PMID- 26826281 TI - Controlled transdermal iontophoresis for poly-pharmacotherapy: Simultaneous delivery of granisetron, metoclopramide and dexamethasone sodium phosphate in vitro and in vivo. AB - Iontophoresis has been used to deliver small molecules, peptides and proteins into and across the skin. In principle, it provides a controlled, non-invasive method for poly-pharmacotherapy since it is possible to formulate and to deliver multiple therapeutic agents simultaneously from the anodal and cathodal compartments. The objective of this proof-of-principle study was to investigate the simultaneous anodal iontophoretic delivery of granisetron (GST) and metoclopramide (MCL) and cathodal iontophoresis of dexamethasone sodium phosphate (DEX-P). In addition to validating the hypothesis, these are medications that are routinely used in combination to treat chemotherapy-induced emesis. Two preliminary in vitro studies using porcine skin were performed: Study 1 - effect of formulation composition on anodal co-iontophoresis of GST and MCL and Study 2 combined anodal iontophoresis of GST (10mM) and MCL (110 mM) and cathodal iontophoresis of DEX-P (40 mM). The results from Study 1 demonstrated the dependence of GST/MCL transport on the respective drug concentrations when co iontophoresed at 0.3 mA.cm(-2). Although they possess similar physicochemical properties, MCL seemed to be a more efficient charge carrier (JMCL=0.0591*CMCLvs JGST=0.0414*CGST). In Study 2, MCL permeation was markedly superior to that of GST (2324.83 +/- 307.85 and 209.83 +/- 24.84 MUg.cm(-2), respectively); this was consistent with the difference in their relative concentrations; DEX-P permeation was 336.94 +/- 71.91 MUg.cm(-2). The in vivo studies in Wistar rats (10mM GST, 110 mM MCL and 40 mM DEX-P (0.5 mA.cm(-2) for 5h with Ag/AgCl electrodes and salt bridges) demonstrated that significant drug levels were achieved rapidly for each drug. This was most noticeable for dexamethasone (DEX) where relatively constant plasma levels were obtained from the 1 to 5h time-points; DEX-P was not detected in the plasma since it was completely hydrolyzed to the active metabolite. The calculated input rates in vivo (k01) for GST, MCL and DEX were 0.45 +/- 0.05, 3.29 +/- 0.48 and 1.97 +/- 0.38 MUg.cm(-2) . min(-1), respectively. The study confirmed that iontophoresis provided a controlled method for the simultaneous administration of multiple therapeutic agents and that it could be of use for poly-pharmacotherapy in general and more specifically that it was able to deliver different drugs used in the treatment of chemotherapy-induced emesis. PMID- 26826283 TI - Neutrophils and arthritis: Role in disease and pharmacological perspectives. AB - The inflammatory response in the joint can induce an intense accumulation of leukocytes in the tissue that frequently results in severe local damage and loss of function. Neutrophils are essential cells to combat many pathogens, but their arsenal can contribute or aggravate articular inflammation. Here we summarized some aspects of neutrophil biology, their role in inflammation and indicated how the modulation of neutrophil functions could be useful for the treatment of different forms of arthritis. PMID- 26826282 TI - Polymorphism and disorder in natural active ingredients. Low and high-temperature phases of anhydrous caffeine: Spectroscopic ((1)H-(14)N NMR-NQR/(14)N NQR) and solid-state computational modelling (DFT/QTAIM/RDS) study. AB - The polymorphism of anhydrous caffeine (1,3,7-trimethylxanthine; 1,3,7-trimethyl 1H-purine-2,6-(3H,7H)-dione) has been studied by (1)H-(14)N NMR-NQR (Nuclear Magnetic Resonance-Nuclear Quadrupole Resonance) double resonance and pure (14)N NQR (Nuclear Quadrupole Resonance) followed by computational modelling (Density Functional Theory, supplemented Quantum Theory of Atoms in Molecules with Reduced Density Gradient) in solid state. For two stable (phase II, form beta) and metastable (phase I, form alpha) polymorphs the complete NQR spectra consisting of 12 lines were recorded. The assignment of signals detected in experiment to particular nitrogen sites was verified with the help of DFT. The shifts of the NQR frequencies, quadrupole coupling constants and asymmetry parameters at each nitrogen site due to polymorphic transition were evaluated. The strongest shifts were observed at N(3) site, while the smallest at N(9) site. The commercial pharmaceutical sample was found to contain approximately 20-25% of phase I and 75 80% of phase II. The orientational disorder in phase II with a local molecular arrangement mimics that in phase I. Substantial differences in the intermolecular interaction phases I and II of caffeine were analysed using computational (DFT/QTAIM/RDS) approach. The analysis of local environment of each nitrogen nucleus permitted drawing some conclusions on the topology of interactions in both polymorphs. For the most stable orientations in phase I and phase II the maps of the principal component qz of EFG tensor and its asymmetry parameter at each point of the molecular system were calculated and visualized. The relevant maps calculated for both phases I and II indicates small variation in electrostatic potential upon phase change. Small differences between packings in phases slightly disturb the neighbourhood of the N(1) and N(7) nitrogens, thus are meaningless from the biological point of view. The composition of two phases in pharmaceutical material should not be any obstacle, which is relevant from the pharmaceutical industry point of view. PMID- 26826284 TI - Harnessing the knowledge of animal toxins to generate drugs. AB - Animal toxins present high selectivity and specificity for their molecular targets, and have long been considered as prototypes for developing novel drugs, with some successful cases. In this regard, the variety of molecules found in animal venoms, which can be capable of affecting vital physiological systems, have providing the development of studies focusing on turning those molecules (toxins) into therapeutics to treat several diseases, such as chronic pain, hypertension, thrombosis, cancer, and so on. However, some important issues have been responsible for disrupting the toxin-based drug discovery projects. In this review, we have briefly highlighted the development of drugs based on animal toxins, discussing some successful cases as well as the main causes of failure, pointing out the recent strategies applied to overcome the difficulties related to the translational process in this kind of development scenario. PMID- 26826285 TI - Registered report: Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. AB - The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from "Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET" by Peinado and colleagues, published in Nature Medicine in 2012 (Peinado et al., 2012). The key experiments being replicated are from Figures 4E, as well as Supplementary Figures 1C and 5A. In these experiments, Peinado and colleagues show tumor exosomes enhance metastasis to bones and lungs, which is diminished by reducing Met expression in exosomes (Peinado et al., 2012). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife. PMID- 26826286 TI - Cloning and characterization of a riboflavin-binding hexamerin from the larval fat body of a lepidopteran stored grain pest, Corcyra cephalonica. AB - In the present study, a riboflavin-binding hexamerin (RbHex) was cloned and characterized from the larval fat body of Corcyra cephalonica. The complete cDNA (2121bp) encodes a 706-amino acid protein with a molecular mass ~82kDa. Expression of RbHex 82 was predominant in fat body among larval tissues. Further, it is prominently expressed during the last instar larval development. Homology modeling and docking studies predicted riboflavin binding site of the hexamerin. Spectrofluorimetric analysis further confirmed riboflavin release from the hexamerin fraction. Quantitative RT-PCR studies demonstrated hormonal regulation of RbHex 82. 20-Hydroxyecdysone (20HE) had a stimulatory effect on its transcription whereas JH alone did not show any effect. However, JH in the presence of 20HE maintains the RbHex 82 expression which indicates the JH's role as a status quo factor. This study is the first to report the characterization of riboflavin-binding hexamerin in a lepidopteran pest. Further, the possibility of RbHex 82 as a pest control target is discussed. PMID- 26826287 TI - Removal of copper(II) using deacetylated konjac glucomannan conjugated soy protein isolate. AB - In this study, an environmentally friendly biosorbent deacetylated konjac glucomannan conjugated soy protein isolate (abbreviated as DKGM-C-SPI) was prepared for Cu(2+) ions removal from aqueous solution. Scanning electron microscopy, Fourier transform infrared spectroscopy and zeta potential analysis revealed successful conjugation of soy protein isolate (SPI) onto deacetylated konjac glucomannan (DKGM) matrix. A comparative adsorption performance of DKGM-C SPI and DKGM was tested to remove Cu(2+) ions from aqueous solution. DKGM-C-SPI showed the desired adsorption performance for Cu(2+) ions. The adsorption equilibrium of DKGM-C-SPI was achieved within 30 min. The adsorption behavior of DKGM-C-SPI followed a pseudo-second-order reaction model. The maximum Cu(2+) ion adsorption capacities obtained from the Langmuir isotherms fit were shown to be 62.50 mg g(-1) for DKGM-C-SPI and 12.23 mg g(-1) for DKGM. This impressive increase about 5 times in Cu(2+) ion adsorption capacity is attributed to the strong Cu(2+) ion chelating ability of the soy protein isolate (SPI) on the DKGM matrix. These results confirm that the DKGM-C-SPI biosorbent has a potential for Cu(2+) ion extraction from wastewater. PMID- 26826288 TI - Removal of Pb(2+) from water environment using a novel magnetic chitosan/graphene oxide imprinted Pb(2+). AB - A novel, magnetic chitosan coating on the surface of graphene oxide was (Pb-MCGO) successfully synthesized using Pb(2+) as imprinted ions for adsorption and removal of Pb(2+) from aqueous solutions. The magnetic composite bioadsorbent was characterized by SEM, FTIR and XRD measurements. Batch adsorption experiments were performed to evaluate the adsorption conditions, selectivity and reusability. The results showed that the maximum adsorption capacity was 79 mg/g, observed at pH 5 and 303K. Equilibrium adsorption was achieved within 40 min. The kinetic data could be fitted with a pseudo-second order equation. Adsorption process could be well described by Langmuir adsorption isotherms. The selectivity coefficient of Pb(2+) and other metal cations onto Pb-MCGO indicated an overall preference for Pb(2+), which was much higher than non-imprinted MCGO beads. Moreover, the sorbent was stable and easily recovered, the adsorption capacity was about 90% of the initial saturation adsorption capacity after being used five times. PMID- 26826289 TI - Mcy protein, a potential antidiabetic agent: evaluation of carbohydrate metabolic enzymes and antioxidant status. AB - The objective of the present study is to elucidate the long-term effects of anti hyperglycemic active principle, Mcy protein (MCP), isolated from the fruits of Momordica cymbalaria on carbohydrate metabolism and oxidative stress in experimental diabetic rats. We used streptozotocin induced diabetic rats for the current studies. Our studies showed that MCP (2.5mg/kg.b.w) treatment significantly normalized the deranged activities of critical carbohydrate metabolizing enzymes, hexokinase, glucose-6-phosphate dehydrogenase, glucose-6 phosphatase and fructose-1,6-bis phosphatase. In addition MCP showed inhibitory activity on alpha-glucosidase and aldose reductase enzymes in in vitro assays. Further MCP treatment improved the antioxidant defensive mechanism by preventing deleterious oxidative products of cellular metabolism, which initiates the lipid peroxidation and by normalizing the antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase) activities. Additional structural studies using circular dichroism spectroscopy indicate that MCP contains majorly alpha helix. Our findings suggest MCP regulates blood glucose and better manage diabetes mellitus associated complications by regulating carbohydrate metabolism and by protecting from the deleterious effects of oxidative stress. PMID- 26826290 TI - Silk fibroin as a non-thrombogenic biomaterial. AB - Silk fibroin (SF), is a very attractive protein-polymer, being processed into a variety of formats to match structural and morphological features for specific biomedical applications. The aim of the present work is to investigate blood compatibility of two forms, films and scaffolds, of silk fibroin-N,N' methylene bisacrylamide (MBA) prepared by using blend solutions of the two components. Biofilms were prepared under UV-irradiation while scaffolds were prepared via freeze-drying technique at -30 degrees C and -80 degrees C, respectively. Swelling, biodegradation tests with protease enzyme, FTIR, SEM, XRD analyses were applied to characterize the biomaterials. The results indicated that, the presence of the crosslinker (MBA) in the scaffold and biofilm aids the formation of ordered structure. The pore size and biodegradability can be controllable by the amount of crosslinker. The anticoagulant activity was evaluated using prothrombin time (PT), activated partial thromboplastin time (APTT). The in-vitro coagulation test and platelet adhesion test analyses indicated that the modified scaffolds and biofilms exhibited better hemocompatibility in comparison with pure silk fibroin. These results demostrated that the silk fibrion-N,N' methylene bisacrylamide biofilms and blended scaffolds have potential applications as blood contact device. PMID- 26826291 TI - Lecithin, gelatin and hydrolyzed collagen orally disintegrating films: functional properties. AB - Orally disintegrating films (ODFs) can transport natural active compounds such as ethanol extract of propolis (EEP). This paper aimed to investigate the effect of lecithin on different gelatin and hydrolyzed collagen (HC) polymeric matrices with addition of EEP. ODFs were prepared by casting technique and were characterized (color parameters, water content, mechanical properties, microstructure, disintegration time (DT), infrared spectroscopy (FTIR), contact angle (CA), swelling degree and total phenolic content). The mechanical properties were influenced by HC. The microstructure demonstrated increased porosity and roughness in films with EEP, and the addition of lecithin resulted in an increase in the number of pores. Lecithin-gelatin and lecithin-EEP-gelatin interactions were observed by FTIR. The addition of HC and EEP reduced the DT and CA, and HC and lecithin reduced the swelling capacity. However, the swelling capacity was not affected by presence of EEP. The addition of lecithin to gelatin and HC ODFs may improve the incorporation and the oral transport of active compounds such as EEP. PMID- 26826292 TI - Polysaccharides from Rhizoma Panacis Majoris and its anti-oxidant activity. AB - Response surface method (RSM) was employed to optimize the extraction conditions of polysaccharides from Rhizoma Panacis Majoris (the rhizomes of Panax japonicus C. A. Mey. var. major (Burk.) C. Y. Wu et K. M. Feng) (RPMP), a well-known Chinese traditional medicine. In order to obtain the optimal processing parameters, a three-variable Box-Behnken designs (BBD) were applied for experimental designs. RSM analysis indicated the good correspondence between experimental and predicted values, the optimal conditions for the yield of polysaccharides were as follows: the ultrasound time is 31.15 min, extraction temperature is 92.50 degrees C, and the ratio of water to raw material is 40 mL/g. The maximum value (13.87 +/- 0.16%) of the yield of polysaccharides was obtained under these optimal conditions. The molecular weight (MW) was determined to be 1.48 * 10(5)(+/-0.39%)Da by HPSEC-MALLS-RID chromatography system. FT-IR spectra demonstrated obvious characteristic peaks of polysaccharides. The antioxidant activities of RPMP were investigated including scavenging activity of hydrogen radicals, ABTS radicals, and free radicals of superoxide anion in vitro, and the results exhibited that RPMP had a good potential for antioxidant. PMID- 26826293 TI - Analysis of Sporothrix schenckii sensu stricto and Sporothrix brasiliensis virulence in Galleria mellonella. AB - The study of the host-pathogen interaction is essential to understand the mechanisms underlying adhesion, colonization and tissue damage by pathogens. This is usually achieved by performing in vivo studies using small mammals, such as rats, mice and guinea pigs. Nowadays, the mouse models of systemic or subcutaneous infection are the gold standard assays to analyze the virulence of members of the Sporothrix schenckii complex. There are, however, invertebrates that have been recently used as alternative hosts to assess the virulence of both bacteria and fungi, and among them, larvae of Galleria mellonella are popular because they are easy to breed, and require non-specialized facilities to maintain the colony. Here, we assessed the use of G. mellonella larvae to test the virulence of S. schenckii sensu stricto and Sporothrix brasiliensis strains, and found that infection with yeast-like cells, but not with conidia or germlings, reproduces the virulence data generated in the mouse model of infection. Furthermore, with this insect model we could classify the virulence of some strains as low, intermediate or high, in line with the observations in the mammalian model. Therefore, G. mellonella is suitable, and a new alternative, to test virulence of both S. schenckii sensu stricto and S. brasiliensis. PMID- 26826294 TI - Hydroxymethyl cytosine marks in the human mitochondrial genome are dynamic in nature. AB - Apart from DNA methylation, hydroxymethylation has increasingly been studied as an important epigenetic mark. 5- hydroxymethylcytosines, though initially were thought to be an intermediary product of demethylation, recent studies suggest this to be a highly regulated process and modulated by the TET family of enzymes. Recent genome wide studies have shown that hydroxymethylcytosine marks are closely associated with the regulation of important biological processes like transcription and embryonic development. It is also known that aberrant hydroxymethylation marks have been associated with diseases like cancer. The presence of hydroxymethylcytosines in the mitochondrial genome has been earlier suggested, though the genome-scale map has not been laid out. In this present study, we have mapped and analyzed the hydroxymethylcytosine marks in the mitochondrial genome using 23 different publicly available datasets. We cross validated our data by checking for consistency across a subset of genomic regions previously annotated to hydroxymethylcytosines and show good consistency. We observe a dynamic distribution of hydroxymethylation marks in the mitochondrial genome. Unlike the methylcytosine marks, hydroxymethylcytosine marks are characterized by the lack of conservation across the samples considered, though similar cell types shared the pattern. We additionally observed that the hydroxymethylation marks are enriched in the upstream of GSS (gene start site) regions and in gene body as similar as nuclear genes. To the best of our knowledge, this is the first genome-scale map of hydroxymethyl cytosines in the human mitochondrial genome. PMID- 26826295 TI - Obesity and Prevalence of Cardiovascular Diseases and Prognosis-The Obesity Paradox Updated. AB - The prevalence and severity of obesity have increased in the United States and most of the Westernized World over recent decades, reaching worldwide epidemics. Since obesity worsens most of the cardiovascular disease (CVD) risk factors, not surprisingly, most CVDs, including hypertension, coronary heart disease, heart failure, and atrial fibrillation, are all increased in the setting of obesity. However, many studies and meta-analyses have demonstrated an obesity paradox with regards to prognosis in CVD patients, with often the overweight and mildly obese having a better prognosis than do their leaner counterparts with the same CVD. The implication for fitness to markedly alter the relationship between adiposity and prognosis and the potential impact of weight loss, in light of the obesity paradox, are all reviewed. PMID- 26826296 TI - AMP-activated protein kinase is involved in perfluorohexanesulfonate-induced apoptosis of neuronal cells. AB - Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds (PFCs), has been used in a variety of industrial and consumer applications and detected in serum in the general population. This raised a concern over its possible detrimental health effects, including neurotoxic effects. We have previously shown that PFHxS induced neuronal apoptosis via the NMDA receptor mediated extracellular signal-regulated kinase (ERK) pathway. Recently, it has been reported that AMP-activated protein kinase (AMPK) acts as a key signal molecule in neuronal excitotoxicity as well as providing a neuroprotective function. In the present study, we have examined the involvement of AMPK in PFHxS induced neuronal apoptosis using neuronal differentiated PC12 cells. PFHxS induced significant increases in intracellular [Ca(2+)] via the NMDA receptor and the L-type voltage-gated calcium channel (L-VGCC). The inhibition of Ca(2+) loading by the NMDA receptor antagonist, MK801 and the L-VGCC blockers, nifedipine and diltiazem significantly reduced PFHxS-induced apoptosis. PFHxS induced sustained activation of AMPK and the inhibition of AMPK activation by compound C and AMPK siRNA significantly reduced PFHxS-induced caspase-3 activity. These results indicate the pro-apoptotic role of AMPK. The activation of AMPK was attenuated by MK801, nifedipine and diltiazem. However, the activation of AMPK was not affected by the ERK inhibitor, PD98059. Likewise, ERK activation was not affected by compound C but was substantially reduced by MK801, nifedipine or diltiazem. This suggests that the activation of AMPK and ERK is regulated by intracellular Ca(2+) loading in distinct pathways. Taken together, PFHxS-induced neuronal apoptosis is mediated by AMPK and ERK pathways, which are distinctly regulated by increased intracellular Ca(2+) via the NMDA receptor and L-VGCC. PMID- 26826297 TI - 3D modeling of human cancer: A PEG-fibrin hydrogel system to study the role of tumor microenvironment and recapitulate the in vivo effect of oncolytic adenovirus. AB - Interactions between malignant and stromal cells and the 3D spatial architecture of the tumor both substantially modify tumor behavior, including the responses to small molecule drugs and biological therapies. Conventional 2D culture systems cannot replicate this complexity. To overcome these limitations and more accurately model solid tumors, we developed a highly versatile 3D PEG-fibrin hydrogel model of human lung adenocarcinoma. Our model relevantly recapitulates the effect of oncolytic adenovirus; tumor responses in this setting nearly reproduce those observed in vivo. We have also validated the use of this model for complex, long-term, 3D cultures of cancer cells and their stroma (fibroblasts and endothelial cells). Both tumor proliferation and invasiveness were enhanced in the presence of stromal components. These results validate our 3D hydrogel model as a relevant platform to study cancer biology and tumor responses to biological treatments. PMID- 26826298 TI - Structure-property relationship for in vitro siRNA delivery performance of cationic 2-hydroxypropyl-beta-cyclodextrin: PEG-PPG-PEG polyrotaxane vectors. AB - Nanoparticle-mediated siRNA delivery is a promising therapeutic approach, however, the processes required for transport of these materials across the numerous extracellular and intracellular barriers are poorly understood. Efficient delivery of siRNA-containing nanoparticles would ultimately benefit from an improved understanding of how parameters associated with these barriers relate to the physicochemical properties of the nanoparticle vectors. We report the synthesis of three Pluronic((r))-based, cholesterol end-capped cationic polyrotaxanes (PR(+)) threaded with 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) for siRNA delivery. The biological data showed that PR(+):siRNA complexes were well tolerated (~90% cell viability) and produced efficient silencing (>80%) in HeLa-GFP and NIH 3T3-GFP cell lines. We further used a multi-parametric approach to identify relationships between the PR(+) structure, PR(+):siRNA complex physical properties, and biological activity. Small angle X-ray scattering and cryoelectron microscopy studies reveal periodicity and lamellar architectures for PR(+):siRNA complexes, whereas the biological assays, zeta potential measurements, and imaging studies suggest that silencing efficiency is influenced by the effective charge ratio (rhoeff), polypropylene oxide (PO) block length, and central PO block coverage (i.e., rigidity) of the PR(+) core. We infer from our findings that more compact PR(+):siRNA nanostructures arising from lower molecular weight, rigid rod-like PR(+) polymer cores produce improved silencing efficiency relative to higher molecular weight, more flexible PR(+) vectors of similar effective charge. This study demonstrates that PR(+):siRNA complex formulations can be produced having higher performance than Lipofectamine((r)) 2000, while maintaining good cell viability and siRNA sequence protection in cell culture. PMID- 26826300 TI - Rational design for enhancing inflammation-responsive in vivo chemiluminescence via nanophotonic energy relay to near-infrared AIE-active conjugated polymer. AB - H2O2-specific peroxalate chemiluminescence is recognized as a potential signal for sensitive in vivo imaging of inflammation but the effect of underlying peroxalate-emitter energetics on its efficiency has rarely been understood. Here we report a simple nanophotonic way of boosting near-infrared chemiluminescence with no need of complicated structural design and synthesis of an energetically favored emitter. The signal enhancement was attained from the construction of a nanoparticle imaging probe (~26 nm in size) by dense nanointegration of multiple molecules possessing unique photonic features, i.e., i) a peroxalate as a chemical fuel generating electronic excitation energy in response to inflammatory H2O2, ii) a low-bandgap conjugated polymer as a bright near-infrared emitter showing aggregation-induced emission (AIE), and iii) an energy gap-bridging photonic molecule that relays the chemically generated excitation energy to the emitter for its efficient excitation. From static and kinetic spectroscopic studies, a green-emissive BODIPY dye has proven to be an efficient relay molecule to bridge the energy gap between the AIE polymer and the chemically generated excited intermediate of H2O2-reacted peroxalates. The energy-relayed nanointegration of AIE polymer and peroxalate in water showed a 50-times boosted sensing signal compared to their dissolved mixture in THF. Besides the high H2O2 detectability down to 10(-9) M, the boosted chemiluminescence presented a fairly high tissue penetration depth (>12 mm) in an ex vivo condition, which enabled deep imaging of inflammatory H2O2 in a hair-covered mouse model of peritonitis. PMID- 26826301 TI - Ultrasound in the diagnosis of calcium pyrophosphate dihydrate deposition disease. A systematic literature review and a meta-analysis. AB - OBJECTIVE: Ultrasonography (US) demonstrated to be a promising tool for the diagnosis of calcium pyrophosphate dihydrate deposition disease (CPPD). The aim of this systematic literature review (SLR) was to collect the definitions for the US elementary lesions and to summarize the available data about US diagnostic accuracy in CPPD. METHODS: We systematically reviewed all the studies that considered US as the index test for CPPD diagnosis without restrictions about the reference test or that provided definitions about US identification of CPPD. Sensitivity and specificity were calculated for each study and definitions were extrapolated. Subgroup analyses were planned by anatomical site included in the index text and different reference standards. RESULTS: Thirty-seven studies were included in this review. All the studies were eligible for the collection of US findings and all definitions were summarized. US description of elementary lesions appeared heterogeneous among the studies. Regarding US accuracy, 13 articles entered in the meta-analysis. Considering each joint structure, the sensitivity ranged between 0.77 (0.63-0.87) and 0.34 (0.16-0.58) while the specificity varies between 1.00 (0.89-1.00) and 0.92 (0.16-1.00). Considering the reference standards used, the sensibility ranged between 0.34 (0.02-0.65) and 0.87 (0.76-0.99) while specificity ranged between 0.84 (0.52-1.00) and 1.00 (0.99 1.00). CONCLUSION: US is potentially a useful tool for the diagnosis of CPPD but universally accepted definitions and further testing are necessary in order to assess the role of the technique in the diagnostic process. PMID- 26826299 TI - Structural and functional evaluation of oxygenating keratin/silk fibroin scaffold and initial assessment of their potential for urethral tissue engineering. AB - In this study, we report a new type of oxygen-generating scaffold, composed of human keratin, silk, gelatin and calcium peroxide (CPO). After mixing the silk/keratin (60:40) with 2% gelatin and 20% CPO, the film demonstrated excellent mechanical properties, non-cytotoxicity and oxygen-generative ability. The detailed structure of scaffold was revealed by confocal laser and electronic scanning microscopy. The gelatin formed the network structure, which mixed with silk fibroin and keratin. The CPOs were embedded into scaffold. A shell-core structure was formed in the CPO particles, in which the CPO was located in the core and the gelatin was mainly wrapped around the CPO. Furthermore, the oxygen release test showed that scaffold was able to steadily release high level of oxygen over two weeks in vitro. In addition, the anti-bacterial function was also proved in the scaffold. Films with CPO enhanced the repair in dog urethral defect models, resulting in patent urethra. Improved organized muscle bundles and epithelial layer were observed in animals treated with CPO films compared with those treated with non-CPO films. This study suggests that this biomaterial could be suitable for tissue engineered urinary tract reconstruction. PMID- 26826302 TI - Hypoxia regulates sumoylation pathways in intervertebral disc cells: implications for hypoxic adaptations. AB - OBJECTIVE: To explore the hypoxic regulation of sumoylation pathways and cell viability in nucleus pulposus (NP) and annulus fibrosus (AF) cells. DESIGN: Expression of small ubiquitin-like modifier (SUMO) molecules, SUMO E1 activating enzymes SAE1 and SAE2, SUMO E2 conjugating enzyme UBC9, and de-sumoylation enzyme sentrin/SUMO-specific proteases (SENP)1 was immunolocalized in rat intervertebral disc (IVD) cells. NP and AF cells were cultured in hypoxia and cell viability was evaluated by quantifying cell proliferation, cellular senescence, apoptosis, and cell cycle distribution. Hypoxic regulation of sumoylation pathways was studied by analyzing the transcription and expression of SUMO molecules and sumoylation enzymes. Loss of function study using SENP1 siRNA was performed to investigate the regulatory role of sumoylation on the function of hypoxia inducible factor 1alpha (HIF-1alpha) and the hypoxic tolerance of IVD cells. RESULTS: Sumoylation pathways were expressed in IVD cells and localized predominantly in nuclei. Both NP and AF cells maintained viability under hypoxia and upregulated the expression of SENP1. In NP cells hypoxia transiently increased the expression of SUMO-1, SUMO-2/3, SAE2, and UBC9, whereas SUMO-1 was elevated while SUMO-2/3, SAE1, SAE2, and UBC9 were reduced by low oxygen tensions in AF cells. Although downregulation of SENP1 decreased the transcriptional activity of HIF-1alpha, the viability of disc cells showed no significant loss under hypoxia. CONCLUSIONS: NP and AF cells equally tolerate oxygen deficiency, but differently regulate the sumoylation pathways under hypoxia. The distinct sumoylation dynamics may help extend our understanding of the cell-specific regulation of the molecular basis that promotes cell survival in the hypoxic IVD. PMID- 26826303 TI - Nanomaterial-dependent immunoregulation of dendritic cells and its effects on biological activities of contraceptive nanovaccines. AB - Nanovehicles are promising delivery systems for various vaccines. Nevertheless, different biophysicochemical properties of nanoparticles (NPs), dominating their in vitro and in vivo performances for vaccination, remain unclear. We attempted to elucidate the effects of NPs and their pH-sensitivity on in vitro and in vivo efficacy of resulting prophylactic nanovaccines containing a contraceptive peptide (FSHR). To this end, pH-responsive and non-responsive nanovaccines were produced using acetalated beta-cyclodextrin (Ac-bCD) and poly(lactic-co-glycolic acid) (PLGA), respectively. Meanwhile, FSHR derived from an epitope of the follicle-stimulating hormone receptor was used as the model antigen. FSHR containing Ac-bCD and PLGA NPs were successfully prepared by a nanoemulsion technique, leading to well-shaped nanovaccines with high loading efficiency. The pH-sensitivity of Ac-bCD and PLGA nanovaccines was examined by in vitro hydrolysis and antigen release studies. Nanovaccines could be effectively engulfed by dendritic cells (DCs) via endocytosis in both dose and time dependent manners, and their intracellular trafficking was closely related to the pH sensitivity of the carrier materials. Furthermore, nanovaccines could induce the secretion of inflammatory cytokines by DCs and T cells co-cultured with the stimulated DCs. In vivo evaluations demonstrated that nanovaccines were more potent than that based on the complete Freund's adjuvant, with respect to inducing anti-FSHR antibody, reducing the sperm count, inhibiting the sperm motility, and increasing the teratosperm rate. Immunization of male mice with nanovaccines notably decreased the parturition incidence of the mated females. Consequently, both in vitro and in vivo activities of FSHR could be considerably augmented by NPs. More importantly, our studies indicated that the pH-responsive nanovaccine was not superior over the non-responsive counterpart for the examined peptide antigen. PMID- 26826304 TI - Hyaluronic acid ion-pairing nanoparticles for targeted tumor therapy. AB - Hyaluronic acid (HA)-based doxorubicin (DOX) nanoparticles (HA-NPs) were fabricated via ion-pairing between positively charged DOX and negatively charged HA, which displayed near-spherical shapes with an average size distribution of 180.2nm (PDI=0.184). Next, HA-NPs were encapsulated in liposomal carriers to afford HA-based DOX liposomes (HA-LPs), which also showed near-spherical morphology with an average size of 130.5nm (PDI=0.201). HA-NPs and HA-LPs displayed desirable sustained-release profiles compared to free DOX, and moreover, HA-LPs were proven to prevent premature release of DOX from HA-NPs. Cell based studies demonstrated HA-NPs and HA-LPs were selectively taken up by CD44(+) tumor cells, and DOX was released intracellularly to target the cell nuclei. Both HA-NPs and HA-LPs showed comparable levels of penetration efficiency in tumor spheroids. In vivo studies revealed that HA-NPs and HA-LPs significantly prolonged the blood circulation time of DOX, decreased accumulation in the normal tissues and enriched drugs into the tumors. Furthermore, HA-NPs and HA-LPs greatly enhanced therapeutic efficacy of DOX in tumor-bearing mice and minimized systemic toxicity against vital organs. In sum, HA-NPs and HA-LPs represent promising nanocarriers for CD44(+) tumor-targeted delivery. PMID- 26826305 TI - Biocomputing nanoplatforms as therapeutics and diagnostics. AB - Biocomputing nanoplatforms are designed to detect and integrate single or multiple inputs under defined algorithms, such as Boolean logic gates, and generate functionally useful outputs, such as delivery of therapeutics or release of optically detectable signals. Using sensing modules composed of small molecules, polymers, nucleic acids, or proteins/peptides, nanoplatforms have been programmed to detect and process extrinsic stimuli, such as magnetic fields or light, or intrinsic stimuli, such as nucleic acids, enzymes, or pH. Stimulus detection can be transduced by the nanomaterial via three different mechanisms: system assembly, system disassembly, or system transformation. The increasingly sophisticated suite of biocomputing nanoplatforms may be invaluable for a multitude of applications, including medical diagnostics, biomedical imaging, environmental monitoring, and delivery of therapeutics to target cell populations. PMID- 26826306 TI - Hypoxia-specific, VEGF-expressing neural stem cell therapy for safe and effective treatment of neuropathic pain. AB - Vascular endothelial growth factor (VEGF) is an angiogenic cytokine that stimulates the differentiation and function of vascular endothelial cells. VEGF has been implicated in improving nervous system function after injury. However, uncontrolled overexpression of VEGF increases the risk of tumor formation at the site of gene delivery. For this reason, VEGF expression needs to be strictly controlled. The goal of the present study was to understand the effects of hypoxia-induced gene expression system to control VEGF gene expression in neural stem cells (NSCs) on the regeneration of neural tissue after sciatic nerve injury. In this study, we used the erythropoietin (Epo) enhancer-SV40 promoter system (EpoSV-VEGF-NSCs) for hypoxia-specific VEGF expression. We used three types of NSCs: DsRed-NSCs as controls, SV-VEGF-NSCs as uncontrolled VEGF overexpressing NSCs, and EpoSV-VEGF-NSCs. For comparison of VEGF expression at normoxia and hypoxia, we measured the amount of VEGF secreted. VEGF expression decreased at normoxia and increased at hypoxia for EpoSV-VEGF-NSCs; thus, EpoSV VEGF-NSCs controlled VEGF expression, dependent upon oxygenation condition. To demonstrate the therapeutic effect of EpoSV-VEGF-NSCs, we transplanted each cell line in a neuropathic pain sciatic nerve injury rat model. The transplanted EpoSV VEGF-NSCs improved sciatic nerve functional index (SFI), mechanical allodynia, and re-myelination similar to the SV-VEGF-NSCs. Additionally, the number of blood vessels increased to a level similar to that of the SV-VEGF-NSCs. However, we did not observe tumor generation in the EpoSV-VEGF-NSC animals that were unlikely to have tumor formation in the SV-VEGF-NSCs. From our results, we determined that EpoSV-VEGF-NSCs safely regulate VEGF gene expression which is dependent upon oxygenation status. In addition, we found that they are therapeutically appropriate for treating sciatic nerve injury. PMID- 26826307 TI - Immune responses to vaccines delivered by encapsulation into and/or adsorption onto cationic lipid-PLGA hybrid nanoparticles. AB - In this study, we used cationic lipid-poly(lactide-co-glycolide) acid (PLGA) hybrid nanoparticles as antigen delivery carriers to investigate how antigen loading methods affect antigen exposure to the immune system and evaluated the resulting antigen-specific immune responses. We formulated three classes of antigen adsorbed and/or encapsulated cationic lipid-PLGA hybrid nanoparticles; we designated antigen-adsorbed (out), antigen-encapsulated (in), and antigen adsorbed/encapsulated (both) nanoparticles. Our results demonstrate significantly more efficient lysosomal escape and cross-presentation of antigen from dendritic cells (DCs) that were exposed to "both" and "in" nanoparticles. In vivo experiments further revealed that "both" nanoparticles significantly more effectively provided not only adequate initial antigen exposure but also long term antigen persistence at the injection site. Data from flow cytometry and ELISA analyses demonstrated elevated in vivo immune responses from mice that were immunized with nanoparticles-delivered OVA when compared with free OVA. In addition, "in" and "both" nanoparticles elicited significantly higher antigen specific immune response than "out" nanoparticles and free OVA. These results suggest that the location of antigen entrapment is an important factor in modulating the immune responses of antigens delivered by nanoparticles. Overall, we propose here a promising approach for the future design of vaccines using cationic lipid-PLGA nanoparticles. PMID- 26826308 TI - Doxorubicin-loaded nanoparticles consisted of cationic- and mannose-modified albumins for dual-targeting in brain tumors. AB - Albumin nanoparticles have been increasingly viewed as an effective way of delivering chemotherapeutics to solid tumors. Here, we report the one-pot development of a unique prototype of doxorubicin-loaded nanoparticles (NPs) made of naive albumin (HSA) plus cationic- (c-HSA) or mannose-modified-albumin (m HSA), with the goal of traversing the blood-brain barrier and targeting brain tumors. c-HSA was synthesized by conjugating ethylenediamine to naive HSA. Then, m-HSA was derivatized using mannopyranoside via a thiol-maleimide reaction. The c/m-HSA NPs were prepared using a mixture solution of c- and m-HSAs in deionized water and doxorubicin in ethanol/chloroform in the same pot using a high-pressure homogenizer. The c/m-HSA NPs were spherical and well-dispersed, with a particle size of 90.5+/-3.1nm and zeta-potential of -12.0+/-0.3mV at c- and m-HSA feed ratios of 5% and 10%, respectively. The c/m-HSA NPs displayed good stability over 3days based on particle size and a linear gradual doxorubicin release over 2days. Specifically, the inhibitory concentration (IC50; 0.5+/-0.02MUg/ml) of c/m-HSA NPs was >2.2-15.6 fold lower than those of doxorubicin or the other HSA NPs. Moreover, among HSA NPs, c/m-HSA NPs exhibited the most prominent performances in transport across the bEnd.3 cell monolayer and uptake in bEnd.3 cells as well as U87MG glioblastoma cells and spheroids. Furthermore, c/m-HSA NPs were localized to a greater extent in brain glioma compared to naive HSA NPs. Orthotopic glioma bearing mice treated with c/m-HSA NPs displayed significantly smaller tumors than the mice treated with saline, doxorubicin or HSA NPs. This improved anti-glioma efficacy seemed to be due to the dual-enhanced system of dual cationic absorptive transcytosis and glucose-transport by the combined use of c- and m-HSAs. The c/m HSA NPs have potential as a novel anti-brain cancer agent with good targetability. PMID- 26826309 TI - One-step encapsulation of siRNA between lipid-layers of multi-layer polycation liposomes by lipoplex freeze-thawing. AB - Small interfering RNA (siRNA) has the potential to be a candidate as a cure for intractable diseases. However, an appropriate vector is required for siRNA delivery because of the low transfection efficiency of siRNA without a vector and its easy degradation in vivo. Here, we report a simple, only one step, and efficient method for siRNA encapsulation into a lipidic nanocarrier by freeze thawing: siRNA was entrapped between the lipid layers of multi-layer liposomes by freeze-thawing of lipoplexes composed of polycation liposomes (PCLs) and siRNA. siRNA-holding capacity to the PCL was increased by repeating freeze-thaw of the lipoplex up to 5cycles. Although siRNA in the conventional lipoplex was degraded after incubation in 90% fetal bovine serum for 72h, siRNA in the frozen and thawed lipoplex was not degraded. Interestingly, we found that the lipoplex formed a "packed multi-layer" structure after the freeze-thawing of "single layer" PCL and siRNA complex, suggesting that siRNA exists between the lipid layers working as a binder. The frozen and thawed lipoplex showed significantly higher knockdown efficacy compared with the conventional lipoplex. In addition, PEGylated freeze-thawed lipoplexes delivered a higher amount of siRNA to a tumor in vivo compared with the PEGylated conventional ones. These results provide an attractive strategy for "one-step" encapsulation of siRNA into liposomes by freeze-thawing. PMID- 26826310 TI - Treating leukemia at the risk of inducing severe anemia. AB - Anemia is a frequently observed adverse effect in cancer patients who receive chemotherapy or drugs designed to block specific oncogenic signaling pathways, although the underlying mechanisms are poorly understood. An article first published online (Zhu HH, Luo X, Zhang K, et al. Proc Natl Acad Sci USA 2015;112:13342-13347) presented data indicating that cell type-specific pathway cross-talk is likely an important mechanism to consider. Shp2 and Pten, two master regulators of central cytoplasmic signaling pathways, oppose each other in myeloproliferation and leukemogenesis, but cooperate in promoting erythropoiesis. Thus, genetic ablation or pharmacologic inhibition of Shp2 suppresses the leukemogenic effect of Pten loss, yet simultaneously induces severe anemia in mice with Pten deficiency in blood cells. PMID- 26826311 TI - Hepatitis C virus infection from the perspective of heterologous immunity. AB - Heterologous immunity can impact the natural course of subsequent infections by different mechanisms such as polarization of TH1/TH2 responses, induction of cytokines and T cell cross-reactivity. In the case of hepatitis C virus (HCV) infection, heterologous immunity helps to explain the high variability in clinical outcomes. This review discusses how other infections can alter the natural course of hepatitis C and how HCV infection influence unrelated infections. PMID- 26826312 TI - Production and characterization of domain-specific monoclonal antibodies against human ECM1. AB - Human extracellular matrix protein-1 (hECM1), a secreted glycoprotein, is widely expressed in different tissues and organs. ECM1 has been implicated in multiple biological functions, which are potentially mediated by the interaction of different ECM1 domains with its ligands. However, the exact biological functions of ECM1 have not been elucidated yet, and the functional study of ECM1 has been partially hampered by the lack of sensitive and specific antibodies, especially those targeting different ECM1 domains. In this study, six strains of monoclonal antibody (MAb) against hECM1 were generated using purified, prokaryotically expressed hECM1 as an immunogen. The MAbs were shown to be highly sensitive and specific, and suitable for western blot, immunoprecipitation assays and immunohistochemistry. Furthermore, the particular ECM1 domains recognized by different MAbs were identified. Lastly, the MAbs were found to have neutralizing activities, inhibiting the proliferation, migration and metastasis of MDA-MB-231 cells. In conclusion, the domain-specific anti-ECM1 MAbs produced in this study should provide a useful tool for investigating ECM1's biological functions, and cellular pathways in which it is involved. PMID- 26826313 TI - An efficient process of generating bispecific antibodies via controlled Fab-arm exchange using culture supernatants. AB - Bispecific antibody generation is actively pursued for therapeutic and research antibody development. Although there are multiple strategies for generating bispecific antibodies (bsAbs); the common challenge is to develop a scalable method to prepare bsAbs with high purity and yield. The controlled Fab-arm exchange (cFAE) method combines two parental monoclonal antibodies (mAbs), each with a matched point mutation, F405L and K409R in the respective CH3 domains. The conventional process employs two steps: the purification of two parental mAbs from culture supernatants followed by cFAE. Following a reduction/oxidation reaction, the bispecific mAb is formed with greater than 95% heterodimerization efficiency. In this study, cFAE was initiated in culture supernatants expressing the two parental mAbs, thereby eliminating the need to first purify the parental mAbs. The bsAbs formed in culture supernatant was then purified using a Protein A affinity chromatography. The BsAbs generated in this manner had efficiency comparable to the conventional method using purified parental mAbs. BsAbs prepared by two different routes showed indistinguishable characteristics by SDS capillary electrophoresis, analytical size exclusion, and cation exchange chromatography. This alternative method significantly shortened timelines and reduced resources required for bsAb generation, providing an improved process with potential benefits in large-scale bsAb preparation, as well as for HTP small scale bsAb matrix selection. PMID- 26826314 TI - Improving the refolding efficiency for proinsulin aspart inclusion body with optimized buffer compositions. AB - Successfully recovering proinsulin's native conformation from inclusion body is the crucial step to guarantee high efficiency for insulin's manufacture. Here, two by-products of disulfide-linked oligomers and disulfide-isomerized monomers were clearly identified during proinsulin aspart's refolding through multiple analytic methods. Arginine and urea are both used to assist in proinsulin refolding, however the efficacy and possible mechanism was found to be different. The oligomers formed with urea were of larger size than with arginine. With the urea concentrations increasing from 2 M to 4 M, the content of oligomers decreased greatly, but simultaneously the refolding yield at the protein concentration of 0.5 mg/mL decreased from 40% to 30% due to the increase of disulfide-isomerized monomers. In contrast, with arginine concentrations increasing up to 1 M, the refolding yield gradually increased to 50% although the content for oligomers also decreased. Moreover, it was demonstrated that not redox pairs but only oxidant was necessary to facilitate the native disulfide bonds formation for the reduced denatured proinsulin. An oxidative agent of selenocystamine could increase the yield up to 80% in the presence of 0.5 M arginine. Further study demonstrated that refolding with 2 M urea instead of 0.5 M arginine could achieve similar yield as protein concentration is slightly reduced to 0.3 mg/mL. In this case, refolded proinsulin was directly purified through one-step of anionic exchange chromatography, with a recovery of 32% and purity up to 95%. All the results could be easily adopted in insulin's industrial manufacture for improving the production efficiency. PMID- 26826316 TI - Production of a soluble and functional recombinant apolipoproteinD in the Pichia pastoris expression system. AB - ApolipoproteinD (ApoD) is a human glycoprotein from the lipocalin family. ApoD contains a conserved central motif of an 8-stranded antiparallel beta-sheet, which forms a beta-barrel that can be used for transport and storage of diverse hydrophobic ligands. Due to hydrophobic nature of ApoD, it has been difficult to generate a recombinant version of this protein. In the present work, we aimed at the production of ApoD in the robust Pichia pastoris expression system. To this end, the ApoD gene sequence was synthesized and subcloned for expression in the yeast host cells. Following integration of the ApoD gene into the yeast genomic region using homologous recombination, the ApoD recombinant protein was induced using methanol, reaching its maximum induction at 96 h. Having purified the ApoD recombinant protein by affinity chromatography, we measured the dissociation constant (KD) using its natural ligands: progesterone and arachidonic acid. Our results provide a viable solution to the production of recombinant ApoD protein in lieu of previous obstacles in generating soluble and functional ApoD protein. PMID- 26826315 TI - Fibulin-1 purification from human plasma using affinity chromatography on Factor H-Sepharose. AB - A method is reported to purify Fibulin-1 from human plasma resulting in a 36% recovery. The steps involve removal of the cryoglobulin and the vitamin K dependent proteins followed by polyethylene glycol and ammonium sulfate precipitations, DEAE-Sephadex column chromatography and finally Factor H Sepharose affinity purification. The procedure is designed to be integrated into an overall scheme for the isolation of over 30 plasma proteins from a single batch of human plasma. Results from mass spectroscopy, SDS-PAGE, and Western blotting indicate that human plasma Fibulin-1 is a single chain of the largest isotype. Functional binding assays demonstrated calcium ion dependent interaction of Fibulin-1 for fibrinogen, fibronectin, and Factor H. The procedure described is the first to our knowledge that enables a large scale purification of Fibulin 1 from human plasma. PMID- 26826317 TI - The role of nitric oxide in the epigenetic regulation of THP-1 induced by lipopolysaccharide. AB - AIMS: Changes in the gene expression are one of the molecular events involved in the Systemic of Inflammatory Response Syndrome during sepsis. The preconditioning with low doses of lipopolysaccharide (LPS) reduces the expression of pro inflammatory genes leading to less tissue damage and better outcome. This hyporesponsive state called tolerance is associated to alterations in chromatin structure and nitric oxide (NO) production. In the current study, we demonstrated that tolerance induced by LPS was found to be NO-dependent and related to epigenetic changes. MAIN METHODS: THP-1 cells were cultivated in RPMI medium (Control), submitted to tolerance (500ng/mL of LPS 24h before challenge with 1000ng/mL of LPS during 24h Tolerant group) and challenge (1000ng/mL of LPS during 24h Directly challenged group). The analyses performed were: cytokines production, histone acetyl transferases/histone deacetylases (HAT/HDAC) activity, nitrosylation of HDAC-2 and -3, expression of acetylated histones H3 and H4. HDAC and Nitric Oxide Synthases (NOS) activities were inhibited with 30mM trichostatin (TSA) and 100MUM LNAME, respectively. KEY FINDINGS: Administration of low doses of LPS repressed the production of IL-6 and IL-10, however this effect was abolished with the inhibition of NOS activity and by TSA in the case of IL-10. Tolerance modulates the activity of HAT and, consequently, the acetylation of histones H3 and H4. Inhibition of NO decreases acetylation of Histones. The HDACs 2 and 3 were nitrosylated after the tolerance induction. SIGNIFICANCE: The tolerance to LPS regulates the cytokine production by modulating chromatin structure and this event is NO dependent. PMID- 26826318 TI - Clinical course and therapeutic implications for lymphoid malignancies in Nijmegen breakage syndrome. AB - Nijmegen breakage syndrome (NBS, MIM #251260) is an autosomal recessive chromosomal instability disorder. Majority of patients affected are of Slavic origin and share the same founder mutation of 657del5 within the NBN gene encoding protein involved in DNA double-strand breaks repair. Clinically, this is characterized by a microcephaly, immunodeficiency and a high incidence of pediatric malignancies, mostly lymphomas and leukemias. Anticancer treatment among patients with NBS is challenging because of a high risk of life threatening therapy-related toxicity including severe infections, bone marrow failure, cardio and nephrotoxicity and occurrence of secondary cancer. Based on systemic review of available literature and the Polish acute lymphoblastic leukemia database we concluded that among patients with NBS, these who suffered from clinically proven severe immunodeficiency are at risk of the complications associated with oncological treatment. Thus, in this group it reasonable to reduce chemotherapy up to 50% especially concerning anthracyclines methotrexate, alkylating agents and epipodophyllotoxines, bleomycin and radiotherapy should be omitted. Moreover, infection prophylaxis using intravenous immunoglobulin supplementation together with antifungal and antibacterial agent is recommended. To replace radiotherapy or some toxic anticancer agents targeted therapy using monoclonal antibodies and kinase inhibitors or bone marrow transplantation with reduced-intensity conditioning should be considered in some cases, however, this statement needs further studies. PMID- 26826319 TI - Neuroprotective effect of curcumin-loaded lactoferrin nano particles against rotenone induced neurotoxicity. AB - Curcumin is known to have neuroprotective role and possess antioxidant, anti inflammatory activities. Rotenone, a flavonoid induced neurotoxicity in dopaminergic cells is being widely studied in Parkinson's Disease (PD) research. In the present study, curcumin loaded lactoferrin nano particles prepared by sol oil chemistry were used to protect dopaminergic cell line SK-N-SH against rotenone induced neurotoxicity. These curcumin loaded nano particles were of 43 60 nm diameter size and around 100 nm hydrodynamic size as assessed by transmission electron microscopy, atomic force microscopy and dynamic light scattering analysis respectively. The encapsulation efficiency was 61.3% +/- 2.4%. Cellular uptake of curcumin through these nano particles was confirmed by confocal imaging and spectrofluorimetric analysis. The curcumin loaded lactoferrin nanoparticles showed greater intracellular drug uptake, sustained retention and greater neuroprotection than soluble counterpart. Neuroprotective activity was characterized through viability assays and by estimating ROS levels. Furthermore rotenone induced PD like features were characterized by decrease in tyrosine hydroxylase expression and increase in alpha-synuclein expression. Taken together curcumin loaded lactoferrin nanoparticles could be a promising drug delivery strategy against neurotoxicity in dopaminergic neurons. PMID- 26826320 TI - Correcting for prematurity affects developmental test scores in infants born late and moderately preterm. AB - BACKGROUND: Corrected age is typically applied when assessing the development of children born <32 weeks of gestation. There is no consensus as to whether corrected age should be applied when assessing children born late/moderately preterm (LMPT; 32-36 weeks of gestation). AIMS: This study explored the impact of corrected age on developmental test scores in infants born LMPT. STUDY DESIGN: 221 LMPT infants were assessed at two years corrected age using the Bayley-III cognitive and language scales, from which cognitive and language composite scores were derived (Normative Mean 100; SD 15). Assessments were then re-scored using chronological age. Bayley-III composite scores <80 were used to define developmental delay. Paired sample t-tests were used to assess the difference in mean test scores derived using corrected versus chronological age, and McNemar's tests to assess the difference in the proportion of infants with developmental delay using corrected versus chronological age. RESULTS: Mean corrected age scores were significantly higher than chronological age scores (cognitive: 2.1 points; 95% CI 1.6, 2.5; language 2.5; 95% CI 2.1, 2.8). Overall, significantly more LMPT infants were classified with developmental delay when chronological (18.3%) versus corrected (15.0%) age was used (p=0.016). CONCLUSIONS: Correcting for prematurity results in significantly higher developmental test scores and a significantly lower prevalence of developmental delay in LMPT infants and may affect eligibility for intervention services. Researchers and clinicians should be aware that the use of corrected age may impact on developmental test scores at both an individual and population level among infants born LMPT. PMID- 26826321 TI - New drostanolone metabolites in human urine by liquid chromatography time-of flight tandem mass spectrometry and their application for doping control. AB - Drostanolone is one of the most frequently detected anabolic androgenic steroids in doping control analysis. Here, we studied drostanolone urinary metabolic profiles using liquid chromatography quadruple time of flight mass spectrometry (LC-QTOF-MS) in full scan and targeted MS/MS modes with accurate mass measurement. The drug was administered to one healthy male volunteer and liquid liquid extraction along with direct-injection were used to analyze urine samples. Chromatographic peaks for potential metabolites were identified with the theoretical [M-H](-) as a target ion in a full scan experiment and actual deprotonated ions were analyzed in targeted MS/MS mode. Eleven metabolites including five new sulfates, five glucuronide conjugates, and one free metabolite were confirmed for drostanolone. Due to the absence of useful fragment ions to illustrate the steroid ring structure of drostanolone phase II metabolites, gas chromatography mass spectrometry (GC-MS) was used to obtain structural details of the trimethylsilylated phase I metabolite released after enzymatic hydrolysis and a potential structure was proposed using a combined MS approach. Metabolite detection times were recorded and S4 (2alpha-methyl-5alpha-androstan-17-one-6beta ol-3alpha-sulfate) and G1 (2alpha-methyl-5alpha-androstan-17-one-3alpha glucuronide) were thought to be new potential biomarkers for drostanolone misuse which can be detected up to 24days by liquid-liquid extraction and 7days by direct-injection analysis after intramuscular injection. S4 and G1 were also detected in two drostanolone-positive routine urine samples. PMID- 26826322 TI - Reversed association between aldosterone and mortality in hemodialysis patients: Role of volume overload. AB - The role of aldosterone has expanded from its genomic effects that involve renal sodium transport to nongenomic effects such as cardiac and renal fibrosis. Elevated aldosterone levels are associated with increased mortality in the general population. However, the association is reversed in patients with end stage renal disease on maintenance hemodialysis. We have shown that the inverse association between aldosterone and mortality in hemodialysis patients is due to the confounding effect of volume overload. Volume overload, which is prevalent in patients with chronic kidney disease, is associated with both lower aldosterone concentrations and higher mortality. Our findings support salt and water restriction and treatment of hyperaldosteronemia in hemodialysis patients who have achieved strict volume control. PMID- 26826323 TI - Baculovirus expression of the N-terminus of porcine heat shock protein Gp96 improves the immunogenicity of recombinant PCV2 capsid protein. AB - Porcine circovirus type 2 (PCV2) causes significant economic losses to the swine industry worldwide. Heat shock proteins (Hsps) can be used as modulators to enhance both innate and adaptive immune responses. In the present study, recombinant baculoviruses expressing the PCV2Cap protein and the N-terminal 22 370 amino acids of porcine Gp96 (Gp96N), Hsp90, and Hsp70 (rBac-cap/Gp96N, rBac cap/Hsp90 and rBac-cap/Hsp70, respectively) were constructed and the immune responses were examined in mice and piglets. The mouse experiments showed that rBac-cap/Gp96N increased the titers of specific anti-PCV2 neutralizing antibodies, proliferative responses of peripheral blood mononuclear cells (PBMCs) and IFN-gamma levels compared to rBac-cap/Hsp90, rBac-cap/Hsp70, or rBac-cap. The pig experiments showed that the levels of anti-PCV2 antibody, proliferative responses of PBMCs, and IFN-gamma in the rBac-cap/Gp96N groups were increased compared to those in rBac-cap group. There were no clear clinical signs of infection following PCV2 challenge in pigs inoculated with recombinant rBac cap/Gp96N and rBac-cap, and the relative daily weight gains were higher than those in the challenge control (CC) group. The pathological lesions, extent of viremia, and viral loads of the vaccinated groups were milder than those in the CC group. Meanwhile, the extent of viremia and viral load present in the rBac cap/Gp96N group were significantly lower than those in the rBac-cap group. These results indicated that porcine Gp96N effectively increased the humoral and cell mediated immune responses of PCV2Cap. Gp96N presents an attractive adjuvant or immunotargeting strategy to enhance the protective efficacy of PCV2 subunit vaccines in swine. PMID- 26826324 TI - The role of local disease perception in the selection of medicinal plants: A study of the structure of local medical systems. AB - ETHNOPHARMACOLOGICAL RELEVANCE: In this study, we investigated the role of local perceptions of diseases in the selection of medicinal plants. For this purpose, we consulted local experts from two communities located in the semiarid region of northeastern Brazil. MATERIALS AND METHODS: After selecting the experts, we used semi-structured interviews to assess the symptoms of each disease studied, the perception of variations in each of these diseases, and the plants used for their treatment. We then conducted a participatory workshop in which the experts engaged in free grouping of the diseases mentioned in the first step. RESULTS: We observed that the therapeutic targets (diseases) showed a lower similarity of medicinal plants than the perceived variants of these targets. We found that plant selection was associated with the perception of symptoms: the greater the similarity between two diseases based on the perceived symptoms, the greater the similarity between these diseases based on the medicinal plants. Furthermore, we observed a greater similarity between plants used to treat diseases perceived as related to each other. CONCLUSION: Local perceptions of the association between diseases and between diseases and symptoms can influence plant selection such that the similarity of the medicinal plants chosen is higher for the diseases perceived as related and as having common symptoms. These results indicate the presence of mechanisms by which local perceptions of diseases affect the structures of local medical systems. PMID- 26826325 TI - Ophiopogon japonicus--A phytochemical, ethnomedicinal and pharmacological review. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Ophiopogonis Radix (Maidong in Chinese), the root of Ophiopogon japonicus, is widely used in local medicines of China, Japan and some south-eastern Asian countries. According to the traditional Chinese medicine (TCM) principle, Ophiopogonis Radix nourishes the yin, promotes body fluid production, moistens the lung, eases the mind and clears away heart fire. This review summarizes the achievements of the investigations in botany, phytochemistry, quality control, traditional uses, pharmacological activities and clinical studies on O. japonicus; this review also describes the shortcomings of studies on this herbal drug and thus serves as the basis of further scientific research and development of this traditional herbal drug. MATERIALS AND METHODS: O. japonicus-related information was collected from various resources, including books on Chinese herbs and the Internet databases, such as Google Scholar, SciFinder, Web of Science, Elsevier, ACS, PubMed and China Knowledge Resource Integrated (CNKI). RESULTS: O. japonicus is widely distributed in East Asia, especially in China. Numerous compounds were identified from this plant. The main components of O. japonicus include steroidal saponins, homoisoflavonoids and polysaccharides, which exhibited various pharmacological activities, such as cardiovascular protection, anti-inflammation, anticancer, anti-oxidation, immunomodulation, cough relief, antimicrobial, and anti-diabetes. CONCLUSIONS: O. japonicus is a common traditional Chinese herbal drug used as the main ingredient in many prescriptions. Modern researches verified that O. japonicus can be used either as a healthy food or a therapeutic agent for disease prevention and treatment. The molecular mechanisms and chemical principles of this herbal medicine should be further explored. PMID- 26826326 TI - Anticonvulsant and sedative-hypnotic activity screening of pearl and nacre (mother of pearl). AB - ETHNOPHARMACOLOGICAL RELEVANCE: Pearl and nacre are valuable traditional medicines to treat palpitations, convulsions or epilepsy in China for thousands of years. However, the active ingredients are not clear till now. AIM OF THE STUDY: The main purpose of the current investigation was to assess the anticonvulsant and sedative-hypnotic activity of pearl powder and nacre powder, including their corresponding 6 protein extracts. MATERIAL AND METHODS: Determination of the amino acid composition of the obtained protein was carried out by ultra-performance liquid chromatography (UPLC) combined with 6 aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) pre-column derivatisation. The influence of the tested drugs on locomotor activity and convulsions latency was recorded. The contents of 5-Hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) in brain were detected by enzyme-linked immunesorbent assay (ELISA) kits. In addition, immunohistochemistry was carried out to evaluate the changes of 5-HT3 and GABAB. In parallel, the expressions of them were demonstrated by western blot. RESULTS: The obtained data suggested that pearl original powder (1.1g/kg), pearl water-soluble protein (0.2g/kg), pearl acid-soluble protein (0.275g/kg), pearl conchiolin protein (1.1g/kg), nacre original powder (1.1g/kg), nacre water-soluble protein (0.2g/kg), nacre acid-soluble protein (0.7g/kg) and nacre conchiolin protein (1.1g/kg) could down-regulate the expression of 5-HT3 and up-regulate the level of GABAB to varying degrees compared with the control group. Besides, drug administration also reduced the locomotor activity and increased convulsions latency with a certain mortality. CONCLUSIONS: These findings correlated with the traditional use of pearl and nacre as sedation and tranquilization agents, thus making them interesting sources for further drug development and also providing critical important evidence for the selection of quality control markers. PMID- 26826327 TI - Effects of Erlong Zuoci decoction on the age-related hearing loss in C57BL/6J mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Erlong Zuoci decoction (ELZCD), a typical traditional Chinese medicine (TCM) prescription, has long been clinically used in treatment of deafness and tinnitus with the syndrome of "kidney yin deficiency". However, there are few studies to investigate its pharmacological mechanisms. Until now, there is not report about its effects on the age-related hearing loss (ARHL). AIM OF STUDY: The present study was conducted to observe the effects of ELZCD on the ARHL in C57BL/6J mice and explore the mechanisms. MATERIALS AND METHODS: ELZCD was fed to C57BL/6J mice from 3 months to 6 months in ELZCD group as a dose of 6g/kg/d. And the same volume of saline was fed to mice in ARHL group. 3-months-old C57BL/6J mice were used as control group. High performance liquid chromatography (HPLC) was used for the quality control of ELZCD. Auditory brainstem response (ABR) was used to assess the hearing function of mice. The morphologic changes were observed by hematoxylin eosin (HE) staining. Apoptosis was tested by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method. Mitochondrial damage was detected by transmission electron microscopy (TEM). Quantitative RT-PCR (qRT-PCR) was used to observe the mRNA expression of p53 and Bak. Fluorescence immunohistochemical technique was used to test the protein expression of p53 and Bak. RESULTS: The hearing threshold of ARHL group was higher than that of control group (P<0.001) and ELZCD decreased the rise of hearing threshold levels of ARHL mice (P<0.001), which suggested ELZCD inhibited the hearing loss of ARHL mice. HE staining showed that ELZCD decreased the spiral ganglion (SG) cell damage and loss in ARHL. TUNEL test showed that the apoptotic SG cells increased in ARHL group compared to control group and decreased in ELZCD group compared to ARHL group. TEM observation showed that mitochondrial damage was obvious in SG cells of ARHL group and ELZCD inhibited the mitochondrial damage. The qRT-PCR results showed that the mRNA expression of p53 and Bak in ARHL group increased compared to that of control group (P<0.05), and ELZCD reduced the elevated mRNA expression levels of p53 and Bak (P<0.01, P<0.05). In addition, ELZCD inhibited the increased proteins expression (green fluorescence) of p53 and Bak. CONCLUSION: The results demonstrated that ELZCD prevented ARHL in C57BL/6J mice and p53/Bak-mediated mitochondrial apoptosis of SG cells might be involved in the mechanisms. PMID- 26826328 TI - Improved tooth bleaching combining ozone and hydrogen peroxide--A blinded study. AB - OBJECTIVES: To evaluate the efficacy of tooth bleaching using ozone after hydrogen peroxide (H2O2) in comparison to the use of H2O2 alone. METHODS: 70 extracted teeth were randomly distributed into two groups. Teeth surfaces in group 1 (n=35) were treated using 38% H2O2 and then were exposed to ozone for 60s and this ozonated peroxide mixture was left on the teeth for 20 min. Meanwhile, teeth in group 2 (n=35) were treated with H2O2 38% for 20 min. The L* a* b* and Vita Classic shade values of teeth were evaluated in both groups at base line, after application of H2O2 and ozone in group 1, and after application of H2O2 and then again after another application of ozone in group 2. The statistically significant changes were set at P <= 0.05. RESULTS: Baseline L* a* b* and Vita shade values were comparable between groups (P>0.05). Teeth obtained lighter shades following bleaching with both H2O2 and ozone or with H2O2 alone (P <= 0.05). Further bleaching with ozone for teeth already bleached with H2O2 alone showed further improvement of the shades of teeth (P<0.001). Teeth treated with H2O2 and ozone had more shade improvements than those only treated with H2O2 (P<0.001). Also, L* values were increased while b* values were decreased (teeth obtained lighter shades) following bleaching in both groups (P <= 0.05). More changes were obtained when both ozone and H2O2 were used (P <= 0.05). CONCLUSIONS: Bleaching with 38% H2O2 and ozone resulted in teeth with lighter shades than bleaching with 38% H2O2 alone. PMID- 26826329 TI - Bulk dentine replacement versus incrementally placed resin composite: A randomised controlled clinical trial. AB - OBJECTIVE: This randomized controlled clinical trial compared two techniques and materials for restoring carious teeth-Bulk dentine replacement versus incremental placement of a hybrid posterior resin composite material in terms of patient comfort (post operative sensitivity and tenderness on biting). MATERIAL AND METHODS: Seventy-two carious teeth were randomized to one of two treatment groups: Group A-were restored with a bulk dentine replacement material or Group B restored with incrementally placed hybrid composite. Patients were followed up by way of a structured phone call at day 2 and day 7 post-operatively. Patients reporting discomfort at day 7 were subsequently followed up on days 14, and 30. RESULTS: All patients were followed up. At day 2, 18/72 restored teeth had post operative sensitivity; this figure fell to 10/72 at day 7. A Chi squared test revealed that at day 2 a greater level of sensitivity was reported by patients in Group A (P=0.029). However, at day 7 there was no statistically significant difference between the two groups in terms of sensitivity (P=0.453). 8/72 and 6 /72 teeth had tenderness to biting at days 2 and 7 respectively. A Chi squared test revealed no statistically significant difference between the two groups in terms of tenderness on biting at any time period (P=0.722). Interestingly, Class I cavities were found to be more tender on biting than Class II cavities. At day 30 2/72 teeth exhibited sensitivity and none of the teeth exhibiting tenderness on biting. CONCLUSION: At day 7 there was no significant difference between the two groups in terms of postoperative sensitivity and tenderness on biting. PMID- 26826330 TI - p38 mitogen-activated protein kinase activation in amygdala mediates kappa opioid receptor agonist U50,488H-induced conditioned place aversion. AB - kappa opioid receptor agonists produce aversive effects in rodents, however the underlying mechanisms remain unclear. Activation of p38 mitogen-activated protein kinase (MAPK) has been discovered to play a critical role in the modulation of affective behaviors. The present study was undertaken to detect the possible involvement of p38 MAPK in the aversive effects induced by kappa opioid receptor activation. We found that the kappa opioid receptor agonist trans-(+/-)-3,4 Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzenacetamide methanesulfonate salt (U50,488H) produced significant place aversion in mice as measured by the conditioned place preference procedure, accompanied with significant p38 MAPK activation in the amygdala, but not in the nucleus accumbens and hippocampus. Stereotaxic microinjection of the p38 MAPK inhibitor 4-(4 fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridy-l)-1H-imidazole (SB203580) into amygdala significantly inhibited p38 MAPK activation and completely blocked the conditioned place aversion in mice. Thus, these results suggested that activation of p38 MAPK in the amygdala was required to mediate kappa opioid receptor-induced aversive behavior. PMID- 26826331 TI - Effect of axotomy and 17beta-estradiol on P2X7 receptor expression pattern in the hypoglossal nucleus of ovariectomized mice. AB - The objective of the study was to examine whether axotomy and 17beta-estradiol affects P2X7 receptor expression and distribution in the hypoglossal nucleus. The left hypoglossal nerve of ovariectomized mice was cut and animals received a single injection of 17beta-estradiol (25 MUg/100g b.w. in 20% (2-hydroxypropyl) beta-cyclodextrin) or vehicle one hour after axotomy. Mice were sacrificed on day 4 following surgery. The area fraction of P2X7 receptor immunoreactive structures and of CD11b immunolabeled microglia, P2X7 protein concentration, and the immunoreactivity pattern of estrogen receptor (ER) alpha/beta were analyzed on both sides of the hypoglossal nucleus. Following axotomy the area fraction of P2X7 immunoreactive neurons showed a decreasing tendency, while the area fraction of P2X7 immunolabeled microglia increased significantly on the axotomized side compared with the control side in mice injected with vehicle. In animals treated with 17beta-estradiol the decrease in area fraction of neural and the increase in area fraction of microglial P2X7 immunostaining on the axotomized side were significantly enhanced compared with animals injected with vehicle. The P2X7 immunoreactivity pattern on the control side of the nucleus remained unchanged after 17beta-estradiol injection. Semi-quantitative Western blots revealed no significant difference in P2X7 protein concentration comparing the axotomized side with the control side in either experimental group. The CD11b immunoreactive microglia area fraction increased significantly following axotomy, but was not affected by 17beta-estradiol. Neither ER alpha, nor beta colocalized with CD11b. Our results suggest that axotomy induces cell-type specific changes in P2X7 receptor expression, which may be directly regulated by 17beta-estradiol through ER alpha or beta in neurons, but not in activated microglia. PMID- 26826332 TI - Minocycline enhances inhibitory transmission to substantia gelatinosa neurons of the rat spinal dorsal horn. AB - Minocycline, a second-generation tetracycline, is well known for its antibiotic, anti-inflammatory, and antinociceptive effects. Modulation of synaptic transmission is one of the analgesic mechanisms of minocycline. Although it has been reported that minocycline may suppress excitatory glutamatergic synaptic transmission, it remains unclear whether it could affect inhibitory synaptic transmission, which also plays a key role in modulating pain signaling. To examine the effect of minocycline on synaptic transmission in rat spinal substantia gelatinosa (SG) neurons, we recorded spontaneous inhibitory postsynaptic currents (sIPSCs) using whole-cell patch-clamp recording at a holding potential of 0 mV. Bath application of minocycline significantly increased the frequency but not the amplitude of sIPSCs in a reversible and concentration-dependent manner with an EC50 of 85. The enhancement of inhibitory synaptic transmission produced by minocycline was not affected by the glutamate receptor antagonists CNQX and D-APV or by the voltage-gated sodium channel blocker tetrodotoxin (TTX). Moreover, the potency of minocycline for facilitating sIPSC frequency was the same in both glycinergic and GABAergic sIPSCs without changing their decay phases. However, the facilitatory effect of minocycline on sIPSCs was eliminated in a Ca(2+)-free Krebs solution or by co-administration with calcium channel blockers. In summary, our data demonstrate that baseline inhibitory synaptic transmission in SG neurons is markedly enhanced by minocycline. This may function to decrease the excitability of SG neurons, thus leading to a modulation of nociceptive transmission. PMID- 26826333 TI - Delta-9-tetrahydrocannabinol (THC) affects forelimb motor map expression but has little effect on skilled and unskilled behavior. AB - It has previously been shown in rats that acute administration of delta-9 tetrahydrocannabinol (THC) exerts a dose-dependent effect on simple locomotor activity, with low doses of THC causing hyper-locomotion and high doses causing hypo-locomotion. However the effect of acute THC administration on cortical movement representations (motor maps) and skilled learned movements is completely unknown. It is important to determine the effects of THC on motor maps and skilled learned behaviors because behaviors like driving place people at a heightened risk. Three doses of THC were used in the current study: 0.2mg/kg, 1.0mg/kg and 2.5mg/kg representing the approximate range of the low to high levels of available THC one would consume from recreational use of cannabis. Acute peripheral administration of THC to drug naive rats resulted in dose dependent alterations in motor map expression using high resolution short duration intracortical microstimulation (SD-ICMS). THC at 0.2mg/kg decreased movement thresholds and increased motor map size, while 1.0mg/kg had the opposite effect, and 2.5mg/kg had an even more dramatic effect. Deriving complex movement maps using long duration (LD)-ICMS at 1.0mg/kg resulted in fewer complex movements. Dosages of 1.0mg/kg and 2.5mg/kg THC reduced the number of reach attempts but did not affect percentage of success or the kinetics of reaching on the single pellet skilled reaching task. Rats that received 2.5mg/kg THC did show an increase in latency of forelimb removal on the bar task, while dose-dependent effects of THC on unskilled locomotor activity using the rotorod and horizontal ladder tasks were not observed. Rats may be employing compensatory strategies after receiving THC, which may account for the robust changes in motor map expression but moderate effects on behavior. PMID- 26826334 TI - Childhood trauma, family history, and their association with mood disorders in early adulthood. AB - OBJECTIVE: To assess the prevalence of childhood trauma and types of trauma on mood disorders among young adults in a population-based sample. We further gathered data on family history of mood disorders to test the hypothesis that childhood trauma is a mediating factor for the association between family history of mood disorder and mood disorder in adulthood. METHOD: This is a cross sectional study, including young adults with bipolar disorder, major depressive disorder, and matched controls without any mood disorder. Childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). The Hicks and Tingley implementation was employed to assess whether trauma is a mediator of the effect of family history on diagnosis of any mood disorder. RESULTS: All types of trauma were associated with both major depression and bipolar disorder, with the exception of sexual abuse, which was only associated with bipolar disorder. Moreover, family history of psychiatric illness was also associated with mood disorder in adulthood and with childhood trauma. Using the presence of any mood disorder as the outcome, a third of the effect of having any family history of mood disorder was mediated via childhood trauma. CONCLUSION: This investigation provides further support, in a population-based sample of young adults, of the association between childhood trauma and mood disorders, with sexual abuse being specifically linked with bipolar disorder. The hypothesis that childhood trauma would function as a partial mediator of the association between family history of mood disorder and mood disorder in adulthood was also confirmed. PMID- 26826336 TI - Introduction to the ECR special issue, "Mechanosensing via Cell-Matrix Adhesions". PMID- 26826335 TI - Site-specific, adult bone benefits attributed to loading during youth: A preliminary longitudinal analysis. AB - We examined site-specific bone development in relation to childhood and adolescent artistic gymnastics exposure, comparing up to 10years of prospectively acquired longitudinal data in 44 subjects, including 31 non-gymnasts (NON) and 13 gymnasts (GYM) who participated in gymnastics from pre-menarche to >=1.9years post-menarche. Subjects underwent annual regional and whole-body DXA scans; indices of bone geometry and strength were calculated. Anthropometrics, physical activity, and maturity were assessed annually, coincident with DXA scans. Non linear mixed effect models centered growth in bone outcomes at menarche and adjusted for menarcheal age, height, and non-bone fat-free mass to evaluate GYM NON differences. A POST-QUIT variable assessed the withdrawal effect of quitting gymnastics. Curves for bone area, mass (BMC), and strength indices were higher in GYM than NON at both distal radius metaphysis and diaphysis (p<0.0001). At the femoral neck, greater GYM BMC (p<0.01), narrower GYM endosteal diameter (p<0.02), and similar periosteal width (p=0.09) yielded GYM advantages in narrow neck cortical thickness and buckling ratio (both p<0.001; lower BR indicates lower fracture risk). Lumbar spine and sub-head BMC were greater in GYM than NON (p<0.036). Following gymnastics cessation, GYM slopes increased for distal radius diaphysis parameters (p<=0.01) and for narrow neck BR (p=0.02). At the distal radius metaphysis, GYM BMC and compressive strength slopes decreased, as did slopes for lumbar spine BMC, femoral neck BMC, and narrow neck cortical thickness (p<0.02). In conclusion, advantages in bone mass, geometry, and strength at multiple skeletal sites were noted across growth and into young adulthood in girls who participated in gymnastics loading to at least 1.9years post-menarche. Following gymnastics cessation, advantages at cortical bone sites improved or stabilized, while advantages at corticocancellous sites stabilized or diminished. Additional longitudinal observation is necessary to determine whether residual loading benefits enhance lifelong skeletal strength. PMID- 26826337 TI - Curcumin inhibits metastasis in human papillary thyroid carcinoma BCPAP cells via down-regulation of the TGF-beta/Smad2/3 signaling pathway. AB - Thyroid cancers usually possess a good prognosis while the risks of recurrence and metastasis turn out to be a disturbing issue. Curcumin [bis(4-hydroxy-3 methoxy-phenyl)-1,6-heptadiene-3,5-dione] is a natural polyphenolic compound mainly found in turmeric (Curcuma longa). Our previous studies have demonstrated that curcumin showed proliferation-inhibitory and apoptosis-inducing effects on K1 papillary thyroid cancer cells. However, the mechanism underlying the inhibition effects of curcumin on thyroid cancer cells remains unclear. Herein, we demonstrated that curcumin remarkably increased the expression of the epithelial marker E-cadherin and repressed the expression of the mesenchymal marker vimentin in human papillary thyroid carcinoma BCPAP cells. Curcumin also suppressed multiple metastatic steps of BCPAP cells, including cell attachment, spreading as well as migration. In addition, the transcription, secretion and activation of matrix metalloproteinases (MMPs) induced by transforming growth factor-beta1 (TGF-beta1) in BCPAP cells were mitigated upon curcumin treatment. Further evidence showed that curcumin decreased TGF-beta1-mediated phosphorylation of Smad2 and Smad3. These results revealed that curcumin inhibited the TGF-beta1-induced epithelial-mesenchymal transition (EMT) via down regulation of Smad2/3 signaling pathways. Our findings provide new evidence that the anti-metastatic and anti-EMT activities of curcumin may contribute to the development of chemo-preventive agents for thyroid cancer treatment. PMID- 26826338 TI - Any value in a specialist review of liver biopsies? Conclusions of a 4-year review. AB - AIMS: Liver pathology is a challenging subspeciality, with histopathologists frequently seeking specialist opinions. This study aims to determine the impact of specialist reviews on the final diagnosis and patient management. METHODS AND RESULTS: Agreement with the initial reporting centre in the histopathological diagnosis of 1265 liver biopsies was determined. The nature of differences was explored in more depth for 103 discrepant cases. Differences in the histopathological interpretation were present in 749 of 1265 (59%) biopsies, of which 505 of 749 (67%) were predicted at the time of reporting to impact upon patient management. Agreement was good in cases with chronic viral hepatitis, fatty liver disease, malignancy and minimal pathological changes, while diagnostic differences occurred in more than 70% with biliary disease, autoimmune hepatitis or vascular/architectural changes. A clinical review of a subset of reports with histopathological differences predicted changes in patient management in 63 of 103 (61%). CONCLUSIONS: Clinically significant differences in liver biopsy interpretation between local pathologists and subspecialists are common. Diagnoses with frequent discrepancies, such as biliary disease, may benefit from a specialist review as standard when diagnosed initially, while cases requiring specialist advice from disease subgroups where discrepancies are less common, such as chronic viral hepatitis, could be selected during the clinicopathological conference process. PMID- 26826339 TI - Environmental factors in the development of autism spectrum disorders. AB - Autism spectrum disorders (ASD) are highly heterogeneous developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication, and obsessive/stereotyped patterns of behavior and repetitive movements. Social interaction impairments are the most characteristic deficits in ASD. There is also evidence of impoverished language and empathy, a profound inability to use standard nonverbal behaviors (eye contact, affective expression) to regulate social interactions with others, difficulties in showing empathy, failure to share enjoyment, interests and achievements with others, and a lack of social and emotional reciprocity. In developed countries, it is now reported that 1%-1.5% of children have ASD, and in the US 2015 CDC reports that approximately one in 45 children suffer from ASD. Despite the intense research focus on ASD in the last decade, the underlying etiology remains unknown. Genetic research involving twins and family studies strongly supports a significant contribution of environmental factors in addition to genetic factors in ASD etiology. A comprehensive literature search has implicated several environmental factors associated with the development of ASD. These include pesticides, phthalates, polychlorinated biphenyls, solvents, air pollutants, fragrances, glyphosate and heavy metals, especially aluminum used in vaccines as adjuvant. Importantly, the majority of these toxicants are some of the most common ingredients in cosmetics and herbicides to which almost all of us are regularly exposed to in the form of fragrances, face makeup, cologne, air fresheners, food flavors, detergents, insecticides and herbicides. In this review we describe various scientific data to show the role of environmental factors in ASD. PMID- 26826340 TI - Closely coupled evolutionary history of ecto- and endosymbionts from two distantly related animal phyla. AB - The level of integration between associated partners can range from ectosymbioses to extracellular and intracellular endosymbioses, and this range has been assumed to reflect a continuum from less intimate to evolutionarily highly stable associations. In this study, we examined the specificity and evolutionary history of marine symbioses in a group of closely related sulphur-oxidizing bacteria, called Candidatus Thiosymbion, that have established ecto- and endosymbioses with two distantly related animal phyla, Nematoda and Annelida. Intriguingly, in the ectosymbiotic associations of stilbonematine nematodes, we observed a high degree of congruence between symbiont and host phylogenies, based on their ribosomal RNA (rRNA) genes. In contrast, for the endosymbioses of gutless phallodriline annelids (oligochaetes), we found only a weak congruence between symbiont and host phylogenies, based on analyses of symbiont 16S rRNA genes and six host genetic markers. The much higher degree of congruence between nematodes and their ectosymbionts compared to those of annelids and their endosymbionts was confirmed by cophylogenetic analyses. These revealed 15 significant codivergence events between stilbonematine nematodes and their ectosymbionts, but only one event between gutless phallodrilines and their endosymbionts. Phylogenetic analyses of 16S rRNA gene sequences from 50 Cand. Thiosymbion species revealed seven well supported clades that contained both stilbonematine ectosymbionts and phallodriline endosymbionts. This closely coupled evolutionary history of marine ecto- and endosymbionts suggests that switches between symbiotic lifestyles and between the two host phyla occurred multiple times during the evolution of the Cand. Thiosymbion clade, and highlights the remarkable flexibility of these symbiotic bacteria. PMID- 26826342 TI - Cord compression and myelopathy due to stress fracture in a patient with diffuse idiopathic skeletal hyperostosis (DISH). PMID- 26826341 TI - Relationship of long noncoding RNA and viruses. AB - Long noncoding (lnc)RNAs comprise a diverse group of transcripts including large intervening noncoding (linc)RNAs, natural antisense transcripts (NATs) and intronic lncRNAs. The functions and mechanisms of more than 200 lncRNAs have been studied in vitro and the results suggest that lncRNAs may be molecular markers of prognosis in cancer patients. Some lncRNAs can promote virus replication and allow escape from cytosolic surveillance to suppress antiviral immunity. For example, lncRNA can cause persistent infection by Theiler's virus, and microRNA (miR)-27a/b is important for efficient murine cytomegalovirus (MCMV) replication. The available evidence suggests that lncRNAs may be potential targets of novel antiviral drugs. PMID- 26826343 TI - Cervical giant pseudomeningocele presented with neck pain: conventional MRI and MR myelography findings. PMID- 26826344 TI - Spinal brucellosis diagnosed with positron emission tomography combined with computed tomography (PET/CT). PMID- 26826345 TI - Spinal bone marrow necrosis after retroperitoneal lymph node dissection. PMID- 26826346 TI - Subcutaneous sacrococcygeal ependymoma in a child. PMID- 26826347 TI - Quality assessment of systematic reviews for surgical treatment of low back pain: an overview. AB - BACKGROUND CONTEXT: Low back pain is one of the most frequent reasons for medical appointments. Surgical treatment is widely controversial, and new surgical techniques and treatment modalities have been developed within the last decade. Treatment for low back pain should be evidence-based through systematic reviews and meta-analysis. Thus, the quality of these reviews is sometimes put into question as methodological mistakes are frequently seen. PURPOSE: The aim of this study was to gather all systematic reviews for the surgical treatment of low back pain and analyze their outcomes, quality, and conclusion. STUDY DESIGN/SETTING: This is an overview of systematic reviews. OUTCOME MEASURES: The outcome measures were the AMSTAR (A MeaSurement Tool to Assess systematic Reviews) score, PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, and conclusion supported by descriptive statistics. METHODS: A literature search for systematic reviews containing low back pain surgical treatment was conducted through different medical databases. Two investigators independently assessed all titles and abstracts for inclusion. Studies should have at least one surgical procedure as an intervention. Diagnoses were categorized as lumbar disc herniation, spondylolisthesis, stenosis, facet joint syndrome, and degenerative disc disease. Quality was assessed through the PRISMA and AMSTAR questionnaires. Study quality related to its PRISMA or AMSTAR score percentage was rated as very poor (<30%), poor (30%-50%), fair (50%-70%), good (70%-90%), and excellent (>90%). Articles were considered conclusive if they had a conclusion for their primary outcome supported by descriptive statistical evidence. This study was funded exclusively by the authors' own resources. None of the authors have any potential conflict of interest to declare. RESULTS: Overall, there were 40 systematic reviews included. According to AMSTAR and PRISMA scores, 5% to 7.5% of the systematic reviews were rated as excellent and most of them were rated as a fair review. AMSTAR indicated that 22.5% of the reviews have very poor quality, whereas PRISMA stated that 7.5% were of very poor quality. For both tools, performing a meta-analysis made the reviews' quality significantly better. The best-rated diagnosis groups according to PRISMA were spondylosis, lumbar disc herniation, and degenerative disc disease. Considering the studies' conclusions, 25 (62.5%) out of the 40 systematic reviews had a conclusion to their primary outcome, and only 11 (27.5%) were supported by descriptive statistical analysis. This means that 44% of the systematic reviews with a conclusion were evidence based. There were 15 (37.5%) systematic reviews that did not reach a conclusion to their primary objectives. CONCLUSIONS: In conclusion, most systematic reviews for low back pain do not reach very good or excellent quality, and only 27.5% of them have evidence-based conclusions. Including a meta-analysis is a significant factor to improve quality and evidence for systematic reviews. PMID- 26826348 TI - Cervical spinal cord herniation. PMID- 26826349 TI - Large thoracic extradural schwannoma atypically invading T2 vertebra. PMID- 26826350 TI - The skin-depigmenting potential of Paeonia lactiflora root extract and paeoniflorin: in vitro evaluation using reconstructed pigmented human epidermis. AB - OBJECTIVE: The roots of the herb Paeonia lactiflora ('White Peony') are used in association with other herbs in traditional clinical cosmetic practice in China as oral treatment for skin pigmentary disorders, such as brown or dark pigmentary spots. However, the skin-depigmenting potential of Paeonia lactiflora root extract and its main ingredient paeoniflorin has been scarcely investigated by topical application. The purpose of this study was to evaluate the efficacy of Paeonia lactiflora root extract and paeoniflorin as skin whitening agent in cosmetic application. METHODS: Paeonia lactiflora root extract (containing 53.25% of paeoniflorin) and paeoniflorin (97% purity) were applied topically on reconstructed pigmented human epidermis model, a three-dimensional (3D) human skin equivalent, showing morphological and functional characteristics similar to those of in vivo human skin. Two specific methods were used for quantifying melanin inside the reconstructed pigmented epidermis: Fontana-Masson staining (2D quantification) and multiphoton microscopy (3D quantification). RESULTS: Compared to vehicle (dimethyl sulfoxide DMSO), a significant decrease in 2D and 3D melanin content was observed after topical application on reconstructed pigmented epidermis of Paeonia lactiflora extract at 300 MUg mL(-1) (-28% and -27%, respectively) and paeoniflorin at 120 MUg mL(-1) /250 MUM (-30% and -23%, respectively), which is in the same order of magnitude as the positive reference 4-n-butylresorcinol at 83 MUg mL(-1) /500 MUM (-26% and -40%, respectively). CONCLUSION: These results demonstrate, for the first time, the depigmenting potential of paeoniflorin and thus the potential interest of using Paeonia lactiflora root extracts containing paeoniflorin in cosmetic or dermatological applications for reducing the severity of some hyperpigmented skin disorders. PMID- 26826351 TI - Multiple ethical review in North-South collaborative research: the experience of the Ebola-Tx trial in Guinea. AB - The process of double ethical review involves the ethics committees (ECs) in the country(ies) of the research site(s) and of the sponsor. This paper aims to assess the experience of the double ethical review in the Ebola-Tx trial, and to make general recommendations for research conducted during public health emergencies. PMID- 26826353 TI - Comparison of approaches for parameter estimation on stochastic models: Generic least squares versus specialized approaches. AB - Parameter estimation for models with intrinsic stochasticity poses specific challenges that do not exist for deterministic models. Therefore, specialized numerical methods for parameter estimation in stochastic models have been developed. Here, we study whether dedicated algorithms for stochastic models are indeed superior to the naive approach of applying the readily available least squares algorithm designed for deterministic models. We compare the performance of the recently developed multiple shooting for stochastic systems (MSS) method designed for parameter estimation in stochastic models, a stochastic differential equations based Bayesian approach and a chemical master equation based techniques with the least squares approach for parameter estimation in models of ordinary differential equations (ODE). As test data, 1000 realizations of the stochastic models are simulated. For each realization an estimation is performed with each method, resulting in 1000 estimates for each approach. These are compared with respect to their deviation to the true parameter and, for the genetic toggle switch, also their ability to reproduce the symmetry of the switching behavior. Results are shown for different set of parameter values of a genetic toggle switch leading to symmetric and asymmetric switching behavior as well as an immigration-death and a susceptible-infected-recovered model. This comparison shows that it is important to choose a parameter estimation technique that can treat intrinsic stochasticity and that the specific choice of this algorithm shows only minor performance differences. PMID- 26826354 TI - Exploring 3D structural influences of aliphatic and aromatic chemicals on alpha cyclodextrin binding. AB - Binding of solutes to macromolecules is often influenced by steric effects caused by the 3D structures of both binding partners. In this study, the 1:1 alpha cyclodextrin (alphaCD) binding constants (Ka1) for 70 organic chemicals were determined to explore the solute-structural effects on the alphaCD binding. Ka1 was measured using a three-part partitioning system with either a headspace or a passive sampler serving as the reference phase. The Ka1 values ranged from 1.08 to 4.97 log units. The results show that longer linear aliphatic chemicals form more stable complexes than shorter ones, and that the position of the functional group has a strong influence on Ka1, even stronger than the type of the functional group. Comparison of linear and variously branched aliphatic chemicals indicates that having a sterically unhindered alkyl chain is favorable for binding. These results suggest that only one alkyl chain can enter the binding cavity. Relatively small aromatic chemicals such as 1,3-dichlorobenzene bind to alphaCD well, while larger ones like tetrachlorobenzene and 3-ring aromatic chemicals show only a weak interaction with alphaCD, which can be explained by cavity exclusion. The findings of this study help interpret cyclodextrin binding data and facilitate the understanding of binding processes to macromolecules. PMID- 26826352 TI - Identification of a binding site of the human immunodeficiency virus envelope protein gp120 to neuronal-specific tubulin. AB - Human immunodeficiency virus-1 (HIV) promotes synaptic simplification and neuronal apoptosis, and causes neurological impairments termed HIV-associated neurological disorders. HIV-associated neurotoxicity may be brought about by acute and chronic mechanisms that still remain to be fully characterized. The HIV envelope glycoprotein gp120 causes neuronal degeneration similar to that observed in HIV-associated neurocognitive disorders subjects. This study was undertaken to discover novel mechanisms of gp120 neurotoxicity that could explain how the envelope protein promotes neurite pruning. Gp120 has been shown to associate with various intracellular organelles as well as microtubules in neurons. We then analyzed lysates of neurons exposed to gp120 with liquid chromatography mass spectrometry for potential protein interactors. We found that one of the proteins interacting with gp120 is tubulin beta-3 (TUBB3), a major component of neuronal microtubules. We then tested the hypothesis that gp120 binds to neuronal microtubules. Using surface plasmon resonance, we confirmed that gp120 binds with high affinity to neuronal-specific TUBB3. We have also identified the binding site of gp120 to TUBB3. We then designed a small peptide (Helix-A) that displaced gp120 from binding to TUBB3. To determine whether this peptide could prevent gp120-mediated neurotoxicity, we cross-linked Helix-A to mesoporous silica nanoparticles (Helix-A nano) to enhance the intracellular delivery of the peptide. We then tested the neuroprotective property of Helix-A nano against three strains of gp120 in rat cortical neurons. Helix-A nano prevented gp120 mediated neurite simplification as well as neuronal loss. These data propose that gp120 binding to TUBB3 could be another mechanism of gp120 neurotoxicity. We propose a novel direct mechanism of human immunodeficiency virus neurotoxicity. Our data show that the viral protein gp120 binds to neuronal specific tubulin beta-3 and blocks microtubule transport. Displacing gp120 from binding to tubulin by a small peptide prevents gp120-mediated neuronal loss. Our study reveals a novel target for developing adjunct therapies against viral infection that promotes neurocognitive disorders. PMID- 26826355 TI - Plasma and CSF oxytocin levels after intranasal and intravenous oxytocin in awake macaques. AB - Oxytocin (OT) is a neuropeptide that mediates a variety of complex social behaviors in animals and humans. Intranasal OT has been used as an experimental therapeutic for human conditions characterized by deficits in social functioning, especially autism spectrum disorder and schizophrenia. However, it is currently under intense debate whether intranasal delivery of OT reaches the central nervous system. In this study, four female rhesus macaques were implanted with chronic intrathecal catheters and used to investigate the pharmacokinetic profile of OT in the central nervous system and the peripheral vasculature following intravenous (IV) and intranasal (IN) administration of OT. In a randomized, crossover design, OT was given to four awake monkeys at three different doses based on body weight (0.1 IU/kg; 1 IU/kg; 5 IU/kg). A time course of concurrent cerebrospinal fluid (CSF) and plasma samples were taken following administration. We found a dose-dependent effect of IV OT treatment on plasma OT levels, which peaked at 5 min post-dose and gradually returned to baseline by 120 min. In contrast, a change in CSF OT was only observed at the highest IV dose (5 IU/kg) at 15 min post-dose and gradually returned to baseline by 120 min. After IN administration, there was no significant change in plasma OT at any of the three doses. However, at the highest dose level, we found a significant increase in CSF OT at 15-30 min post- dose. The results of this study in light of recent, similar publications highlight the importance of methodological consistency across studies. This study also establishes a non-human primate model that can provide a stable platform for carrying out serial sampling from the central nervous system and peripheral vasculature concurrently. PMID- 26826356 TI - Comparative study of inorganic elements determined in whole blood from Dmd(mdx)/J mice strain by EDXRF and NAA analytical techniques. AB - Several diseases can be diagnosed observing the variation of specific elements concentration in body fluids. In this study the concentration of inorganic elements in blood samples of dystrophic (Dmd(mdx)/J) and C57BL/6J (control group) mice strain were determined. The results obtained from Energy Dispersive X-ray Fluorescence (EDXRF) were compared with Neutron Activation Analysis (NAA) technique. Both analytical techniques showed to be appropriate and complementary offering a new contribution for veterinary medicine as well as detailed knowledge of this pathology. PMID- 26826357 TI - Are bee diseases linked to pesticides? - A brief review. AB - The negative impacts of pesticides, in particular insecticides, on bees and other pollinators have never been disputed. Insecticides can directly kill these vital insects, whereas herbicides reduce the diversity of their food resources, thus indirectly affecting their survival and reproduction. At sub-lethal level ( roe deer > wild boar. PCDD/Fs were the dominant congeners in TEQ value. For all tested species, the dominant contributors to the total WHO-TEQ were PCB-126, 2,3,4,7,8-PeCDF and 1,2,3,7,8-PeCDD. Among the PCDD/F congeners in the deer tissues, OCDD, OCDF and 2,3,4,7,8-PeCDF were dominant, while in wild boar, OCDD, 1,2,3,4,6,7,8-HpCDD and 1,2,3,4,6,7,8-HpCF occurred in the highest amounts. Among PCBs, PCB-105, 118, 156, 138, 153 and 180 were dominant in all species, but with different levels. The regular consumption of muscle meat from game animals should not cause unacceptable dioxin intake above the Tolerable Weekly Intake (TWI) value for children and adults. However, liver consumption should be avoided, especially by children and pregnant or lactating women. High consumption of contaminated liver may cause dioxin intake at levels up to 300% of TWI for adults and up to 700% TWI for children. PMID- 26826360 TI - Mechanisms of housedust-induced toxicity in primary human corneal epithelial cells: Oxidative stress, proinflammatory response and mitochondrial dysfunction. AB - Human cornea is highly susceptible to damage by dust. Continued daily exposure to housedust has been associated with increasing risks of corneal injury, however, the underlying mechanism has not been elucidated. In this study, a composite housedust sample was tested for its cytotoxicity on primary human corneal epithelial (PHCE) cells, which were exposed to dust at 5-320MUg/100MUL for 24h. PHCE cell viability showed a concentration-dependent toxic effect, attributing to elevated intracellular ROS. Moreover, when exposed at >20-80MUg/100MUL, dust induced oxidative damage was evidenced by increased malondialdehyde and 8-hydroxy 2-deoxyguanosine (1.3-2.3-fold) and decreased antioxidative capacity (1.6-3.5 fold). Alteration of mRNA expression of antioxidant enzymes (SOD1, CAT, HO-1, TRXR1, GSTM1, GSTP1, and GPX1) and pro-inflammatory mediators (IL-1beta, IL-6, IL 8, TNF-alpha, and MCP-1) were also observed. Furthermore, the mitochondrial transmembrane potential was dissipated from 9.2 to 82%. Our results suggested that dust-induced oxidative stress probably played a vital role in the cytotoxicity in PHCE cells, which may have contributed to dust-induced impairment of human cornea. PMID- 26826361 TI - Brominated flame retardants (BFRs) in breast milk and associated health risks to nursing infants in Northern Tanzania. AB - The main aim of this study was to assess brominated flame retardants (BFRs) in breast milk in the Northern parts of Tanzania. Ninety-five colostrum samples from healthy, primiparous mothers at Mount Meru Regional Referral Hospital (MMRRH), Arusha Tanzania, were analyzed for polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE), hexabromobenzene (HBB), (2,3-dibromopropyl) (2,4,6-tribromophenyl) ether (DPTE), pentabromoethylbenzene (PBEB) and 2,3,4,5,6-pentabromotoluene (PBT). The ?7PBDE (BDE 28, 47, 99, 100, 153, 154, 183) ranged from below level of detection (99% of the estimated daily intake (EDI) for the general population. The isomeric profiles of PFOA and PFOS in human serum were predicted based on the EDI and a one-compartment, first-order pharmacokinetic model. The isomeric percentage of n-PFOA in the EDI (98.6%) was similar to that in human serum (predicted: 98.2%, previously measured: 99.7%) of Tianjin residents. The results suggest direct PFOA intake plays an important role in its isomeric compositions in humans. For PFOS, the predicted n-PFOS (69.3%) was much higher than the previously measured values (59.2%) in human serum. This implies that other factors, such as indirect exposure to PFOS precursors and multiple excretion pathways, may contribute to the lower percentage of n-PFOS in humans than of technical PFOS. PMID- 26826364 TI - Alternaria alternata allergens: Markers of exposure, phylogeny and risk of fungi induced respiratory allergy. AB - Alternaria alternata spores are considered a well-known biological contaminant and a very common potent aeroallergen source that is found in environmental samples. The most intense exposure to A. alternata allergens is likely to occur outdoors; however, Alternaria and other allergenic fungi can colonize in indoor environments and thereby increase the fungal aeroallergen exposure levels. A consequence of human exposure to fungal aeroallergens, sensitization to A. alternata, has been unequivocally associated with increased asthma severity. Among allergenic proteins described in this fungal specie, the major allergen, Alt a 1, has been reported as the main elicitor of airborne allergies in patients affected by a mold allergy and considered a marker of primary sensitization to A. alternata. Moreover, A. alternata sensitization seems to be a triggering factor in the development of poly-sensitization, most likely because of the capability of A. alternata to produce, in addition to Alt a 1, a broad and complex array of cross-reactive allergens that present homologs in several other allergenic sources. The study and understanding of A. alternata allergen information may be the key to explaining why sensitization to A. alternata is a risk factor for asthma and also why the severity of asthma is associated to this mold. Compared to other common environmental allergenic sources, such as pollens and dust mites, fungi are reported to be neglected and underestimated. The rise of the A. alternata allergy has enabled more research into the role of this fungal specie and its allergenic components in the induction of IgE-mediated respiratory diseases. Indeed, recent research on the identification and characterization of A. alternata allergens has allowed for the consideration of new perspectives in the categorization of allergenic molds, assessment of exposure and diagnosis of fungi-induced allergies. PMID- 26826365 TI - Applying network analysis and Nebula (neighbor-edges based and unbiased leverage algorithm) to ToxCast data. AB - BACKGROUND: ToxCast data have been used to develop models for predicting in vivo toxicity. To predict the in vivo toxicity of a new chemical using a ToxCast data based model, its ToxCast bioactivity data are needed but not normally available. The capability of predicting ToxCast bioactivity data is necessary to fully utilize ToxCast data in the risk assessment of chemicals. OBJECTIVES: We aimed to understand and elucidate the relationships between the chemicals and bioactivity data of the assays in ToxCast and to develop a network analysis based method for predicting ToxCast bioactivity data. METHODS: We conducted modularity analysis on a quantitative network constructed from ToxCast data to explore the relationships between the assays and chemicals. We further developed Nebula (neighbor-edges based and unbiased leverage algorithm) for predicting ToxCast bioactivity data. RESULTS: Modularity analysis on the network constructed from ToxCast data yielded seven modules. Assays and chemicals in the seven modules were distinct. Leave-one out cross-validation yielded a Q(2) of 0.5416, indicating ToxCast bioactivity data can be predicted by Nebula. Prediction domain analysis showed some types of ToxCast assay data could be more reliably predicted by Nebula than others. CONCLUSIONS: Network analysis is a promising approach to understand ToxCast data. Nebula is an effective algorithm for predicting ToxCast bioactivity data, helping fully utilize ToxCast data in the risk assessment of chemicals. PMID- 26826366 TI - ATR-FTIR spectroscopy reveals polycyclic aromatic hydrocarbon contamination despite relatively pristine site characteristics: Results of a field study in the Niger Delta. AB - Fourier-transform infrared (FTIR) spectroscopy is an emerging technique to detect biochemical alterations in biological tissues, particularly changes due to sub lethal exposures to environmental contaminants. We have previously shown the potential of attenuated total reflection FTIR (ATR-FTIR) spectroscopy to detect real-time exposure to contaminants in sentinel organisms as well as the potential to relate spectral alterations to the presence of specific environmental agents. In this study based in the Niger Delta (Nigeria), changes occurring in fish tissues as a result of polycyclic aromatic hydrocarbon (PAH) exposure at contaminated sites are compared to the infrared (IR) spectra of the tissues obtained from a relatively pristine site. Multivariate analysis revealed that PAH contamination could be occurring at the pristine site, based on the IR spectra and significant (P<0.0001) differences between sites. The study provides evidence of the IR spectroscopy techniques' sensitivity and supports their potential application in environmental biomonitoring. PMID- 26826367 TI - High resolution exposure modelling of heat and air pollution and the impact on mortality. AB - BACKGROUND: Elevated temperature and air pollution have been associated with increased mortality. Exposure to heat and air pollution, as well as the density of vulnerable groups varies within cities. The objective was to investigate the extent of neighbourhood differences in mortality risk due to heat and air pollution in a city with a temperate maritime climate. METHODS: A case-crossover design was used to study associations between heat, air pollution and mortality. Different thermal indicators and air pollutants (PM10, NO2, O3) were reconstructed at high spatial resolution to improve exposure classification. Daily exposures were linked to individual mortality cases over a 15year period. RESULTS: Significant interaction between maximum air temperature (Tamax) and PM10 was observed. During "summer smog" days (Tamax>25 degrees C and PM10>50MUg/m(3)), the mortality risk at lag 2 was 7% higher compared to the reference (Tamax 15 degrees C and PM10 15MUg/m(3)). Persons above age 85 living alone were at highest risk. CONCLUSION: We found significant synergistic effects of high temperatures and air pollution on mortality. Single living elderly were the most vulnerable group. Due to spatial differences in temperature and air pollution, mortality risks varied substantially between neighbourhoods, with a difference up to 7%. PMID- 26826368 TI - Perceptions of branded and plain cigarette packaging among Mexican youth. AB - Plain cigarette packaging, which seeks to remove all brand imagery and standardize the shape and size of cigarette packs, represents a novel policy measure to reduce the appeal of cigarettes. Plain packaging has been studied primarily in high-income countries like Australia and the UK. It is unknown whether the effects of plain packaging may differ in low-and-middle income countries with a shorter history of tobacco regulation, such as Mexico. An experimental study was conducted in Mexico City to examine perceptions of branded and plain cigarette packaging among smoking and non-smoking Mexican adolescents (n = 359). Respondents were randomly assigned to a branded or plain pack condition and rated 12 cigarette packages for appeal, taste, harm to health and smoker-image traits. As a behavioral measure of appeal, respondents were offered (although not given) four cigarette packs (either branded or plain) and asked to select one to keep. The findings indicated that branded packs were perceived to be more appealing (beta = 3.40, p < 0.001) and to contain better tasting cigarettes (beta = 3.53, p < 0.001), but were not perceived as less harmful than plain packs. Participants rated people who smoke the branded packs as having relatively more positive smoker-image traits overall (beta = 2.10, p < 0.001), with particularly strong differences found among non-smokers for the traits 'glamorous', 'stylish', 'popular' and 'sophisticated' (p < 0.001). No statistically significant difference was found for the proportion of youth that accepted when offered branded compared with plain packs. These results suggest that plain packaging may reduce brand appeal among Mexican youth, consistent with findings in high-income countries. PMID- 26826369 TI - Device-identified atrial fibrillation at pacing clinics. Should it guide anticoagulation? AB - In recent years, there has been a significant increase in the number of devices implanted following improvement in their safety profile, extension of indications and reduction in cost. Although the reason remains largely the beneficial effect on heart rhythm stabilisation, implanted devices might also have additional advantages, notably identification of silent arrhythmia. Should clinicians therefore act on device-identified atrial fibrillation (AF) and should such identification be used to guide anticoagulation management? This review evaluates the current evidence on the management of device-identified asymptomatic AF. PMID- 26826370 TI - Relation Between Health-Related Quality of Life and Sleep Quality With Adjustment for Comorbidity Among the Korean Elderly: Mixed-Effects Model With a 6-Year Follow-up Study. AB - It is an important public health problem to identify risk factors of health related quality of life (HRQoL) among the elderly. We recruited subjects from Ansan, Korea, as a subset of the Korean Genome and Epidemiology Study (KoGES), which is an ongoing population study, and followed up their sleep quality for 6 years. Mixed effect models were used to estimate the association between sleep quality and HRQoL, and we found that overall HRQoL was significantly lower to the elderly having poor sleep quality with adjustment for significant covariates although sleep quality showed a significant interaction effect with time for the mental component summary of SF-12. In particular, the elderly having lack of quality sleep appeared to have good general health, but their functional performances were significantly poor. PMID- 26826371 TI - Purification and characterization of recombinant sugarcane sucrose phosphate synthase expressed in E. coli and insect Sf9 cells: an importance of the N terminal domain for an allosteric regulatory property. AB - Sucrose phosphate synthase (SPS) catalyses the transfer of glycosyl group of uridine diphosphate glucose to fructose-6-phosphate to form sucrose-6-phosphate. Plant SPS plays a key role in photosynthetic carbon metabolisms, which activity is modulated by an allosteric activator glucose-6-phosphate (G6P). We produced recombinant sugarcane SPS using Escherichia coli and Sf9 insect cells to investigate its structure-function relationship. When expressed in E. coli, two forms of SPS with different sizes appeared; the larger was comparable in size with the authentic plant enzyme and the shorter was trimmed the N-terminal 20 kDa region off. In the insect cells, only enzyme with the authentic size was produced. We purified the trimmed SPS and the full size enzyme from insect cells and found their enzymatic properties differed significantly; the full size enzyme was activated allosterically by G6P, while the trimmed one showed a high activity even without G6P. We further introduced a series of N-terminal truncations up to 171 residue and found G6P-independent activity was enhanced by the truncation. These combined results indicated that the N-terminal region of sugarcane SPS is crucial for the allosteric regulation by G6P and may function like a suppressor domain for the enzyme activity. PMID- 26826373 TI - Fatal Primaquine-Induced Hemolysis in a Patient With Plasmodium vivax Malaria and G6PD A(-) Variant in the Brazilian Amazon. PMID- 26826374 TI - Streptococcal Infections and Varicella. PMID- 26826372 TI - CD4 Cell Count: Declining Value for Antiretroviral Therapy Eligibility. AB - Antiretroviral therapy (ART) policy for people living with human immunodeficiency virus (HIV) has historically been based on clinical indications, such as opportunistic infections and CD4 cell counts. Studies suggest that CD4 counts early in HIV infection do not predict relevant public health outcomes such as disease progression, mortality, and HIV transmission in people living with HIV. CD4 counts also vary widely within individuals and among populations, leading to imprecise measurements and arbitrary ART initiation. To capture the clinical and preventive benefits of treatment, the global HIV response now focuses on increasing HIV diagnosis and ART coverage. CD4 counts for ART initiation were necessary when medications were expensive and had severe side effects, and when the impact of early ART initiation was unclear. However, current evidence suggests that although CD4 counts may still play a role in guiding clinical care to start prophylaxis for opportunistic infections, CD4 counts should cease to be required for ART initiation. PMID- 26826375 TI - Probiotics as Antifungals in Mucosal Candidiasis. AB - Candidais an opportunistic pathogen that causes mucosal and deep systemic candidiasis. The emergence of drug resistance and the side effects of currently available antifungals have restricted their use as long-term prophylactic agents for candidal infections. Given this scenario, probiotics have been suggested as a useful alternative for the management of candidiasis. We analyzed the available data on the efficacy of probiotics in candidal colonization of host surfaces. A number of well-controlled studies indicate that probiotics, particularly lactobacilli, suppressCandidagrowth and biofilm development in vitro.A few clinical trials have also shown the beneficial effects of probiotics in reducing oral, vaginal, and enteric colonization byCandida; alleviation of clinical signs and symptoms; and, in some cases, reducing the incidence of invasive fungal infection in critically ill patients. Probiotics may serve in the future as a worthy ally in the battle against chronic mucosal candidal infections. PMID- 26826376 TI - Improved Measles Vaccination: Contributions of a Travel Clinic. PMID- 26826377 TI - Reply. PMID- 26826378 TI - Calreticulin secures calcium-dependent nuclear pore competency required for cardiogenesis. AB - Calreticulin deficiency causes myocardial developmental defects that culminate in an embryonic lethal phenotype. Recent studies have linked loss of this calcium binding chaperone to failure in myofibrillogenesis through an as yet undefined mechanism. The purpose of the present study was to identify cellular processes corrupted by calreticulin deficiency that precipitate dysregulation of cardiac myofibrillogenesis related to acquisition of cardiac phenotype. In an embryonic stem cell knockout model, calreticulin deficit (crt(-/-)) compromised nucleocytoplasmic transport of nuclear localization signal-dependent and independent pathways, disrupting nuclear import of the cardiac transcription factor MEF2C. The expression of nucleoporins and associated nuclear transport proteins in derived crt(-/-) cardiomyocytes revealed an abnormal nuclear pore complex (NPC) configuration. Altered protein content in crt(-/-) cells resulted in remodeled NPC architecture that caused decreased pore diameter and diminished probability of central channel occupancy versus wild type counterparts. Ionophore treatment of impaired calcium handling in crt(-/-) cells corrected nuclear pore microarchitecture and rescued nuclear import resulting in normalized myofibrillogenesis. Thus, calreticulin deficiency alters nuclear pore function and structure, impeding myofibrillogenesis in nascent cardiomyocytes through a calcium dependent mechanism. This essential role of calreticulin in nucleocytoplasmic communication competency ties its regulatory action with proficiency of cardiac myofibrillogenesis essential for proper cardiac development. PMID- 26826379 TI - Proteolysis targeting peptide (PROTAP) strategy for protein ubiquitination and degradation. AB - Ubiquitination proteasome pathway (UPP) is the most important and selective way to degrade proteins in vivo. Here, a novel proteolysis targeting peptide (PROTAP) strategy, composed of a target protein binding peptide, a linker and a ubiquitin E3 ligase recognition peptide, was designed to recruit both target protein and E3 ligase and then induce polyubiquitination and degradation of the target protein through UPP. In our study, the PROTAP strategy was proved to be a general method with high specificity using Bcl-xL protein as model target in vitro and in cells, which indicates that the strategy has great potential for in vivo application. PMID- 26826380 TI - Involvement of endogenous neuromedin U and neuromedin S in thermoregulation. AB - We investigated the possible involvement of neuromedin U (NMU) and neuromedin S (NMS) in thermoregulation in rats. Intracerebroventricular (icv) injection of NMU or NMS increased the back surface temperature (BS-T) in a dose-dependent manner during both the light and dark periods. Pre-treatment with the beta3 blocker SR59230A, and the cyclooxygenase blocker indomethacin, inhibited the increase in BS-T induced by NMS. Icv injection of NMS and NMU increased the expression of mRNAs for prostaglandin E synthase and cyclooxygenase 2 (COX2) in the hypothalamus, and that of mRNA for uncoupling protein 1 (UCP1) in the brown adipose tissue. Comparison of thermogenesis in terms of body temperature under normal and cold conditions revealed that NMS-KO and double-KO mice had a significantly low BS-T during the active phase, whereas NMU-KO mice did not. Exposure to low temperature decreased the BS temperature in all KO mice, but BS-T was lower in NMS-KO and double-KO mouse than in NMU-KO mice. Calorie and oxygen consumption was also significantly lower in all KO mice than in wild-type mice during the dark period. These results suggest that NMU and NMS are involved in thermoregulation via the prostaglandin E2 and beta3 adrenergic receptors, but that endogenous NMS might play a more predominant role than NMU. PMID- 26826381 TI - MTERF2 contributes to MPP(+)-induced mitochondrial dysfunction and cell damage. AB - Parkinson's disease (PD) is a common neurodegenerative disorder whose pathogenesis is under intense investigation. Substantial evidence indicates that mitochondrial dysfunction plays a central role in the pathophysiology of PD. Several mitochondrial internal regulating factors act to maintain the mitochondrial function. However, how these internal regulating factors contribute to mitochondrial dysfunction in PD remains elusive. One of these factors, mitochondrial transcription termination factor 2 (MTERF2), has been implicated in the regulation of oxidative phosphorylation by modulating mitochondrial DNA transcription. Here, we discovered a new role of MTERF2 in regulating mitochondrial dysfunction and cell damage induced by MPP(+) in SH-SY5Y cells. We found that MPP(+) treatment elevated MTERF2 expression, induced mitochondrial dysfunction and cell damage, which was alleviated by MTERF2 knockdown. These findings demonstrate that MTERF2 contributes to MPP(+)-induced mitochondrial disruption and cell damage. This study indicates that MTERF2 is a potential therapeutic target for environmentally induced Parkinson's disease. PMID- 26826382 TI - Linagliptin but not Sitagliptin inhibited transforming growth factor-beta2 induced endothelial DPP-4 activity and the endothelial-mesenchymal transition. AB - Dipeptidyl peptidase (DPP)-4 plays an important role in endothelial cell biology. We have shown that the DPP-4 inhibitor Linagliptin can inhibit the endothelial mesenchymal transition (EndMT) and ameliorate diabetic kidney fibrosis associated with the suppression of DPP-4 protein levels via the induction of miR-29. The current study demonstrated that such effects of Linagliptin on endothelial cell profibrotic programs were drug-specific but not class effects. In the cell-free system, both Linagliptin and Sitagliptin inhibited recombinant DPP-4 activity in a concentration-dependent manner. Linagliptin can inhibit all of the following: DPP-4 activity and protein level, integrin beta1 protein levels, EndMT, and DPP-4 3'UTR activity; Sitagliptin, however, inhibited none of these in the current study. Additionally, TGF-beta2 induced both the induction of VEGF-R1 and the suppression of VEGF-R2 levels in endothelial cells, and both were inhibited by Linagliptin but not by Sitagliptin. miR-29, the miR that negatively regulates the 3'UTR of DPP-4 mRNA, was suppressed by TGF-beta2 and restored by Linagliptin but not by Sitagliptin. Following the overexpression of pCMV-DPP-4-GFP and pCMV6-Myc DPP-4 in endothelial cells, the proximity of Myc-DPP-4 and DPP-4-GFP was suppressed by Linagliptin but not by Sitagliptin, suggesting that only Linagliptin inhibited the homo-dimer formation of DPP-4 in endothelial cells; this difference in activity between the two gliptins could explain their diverse effects on endothelial cell biology. In conclusion, each of the DPP-4 inhibitors may have unique drug-specific effects. PMID- 26826383 TI - Cancer-associated fibroblasts attenuate Cisplatin-induced apoptosis in ovarian cancer cells by promoting STAT3 signaling. AB - One of the main reasons for treatment failure in ovarian cancer is acquired drug resistance. Cancer associated fibroblasts (CAFs) are known to enhance chemoresistance in many human tumors. However, its contributions to chemoresistance acquisition in ovarian cancer are not well understood. Here, we provide the first evidence that the conditioned medium of CAFs (CAFs-CM) could attenuate the sensitivity to Cisplatin in A2780 and ES2 ovarian cancer cells and protect them from Cisplatin-induced apoptosis. We found the expression level of two anti-apoptotic proteins, Bcl-2 and Survivin, as well as their upstream controller p-STAT3 were significantly increased when ovarian cancer cells were exposed to CAFs-CM. Furthermore, inhibition of STAT3 signaling with Cryptotanshinone could down-regulate the expression of Bcl-2 and Survivin, thus weaken the post-target resistance to Cispaltin mediating by CAFs-CM in ovarian cancer cells. In conclusion, our data suggested that CAFs could activate the anti apoptotic STAT3 signaling, thereby decrease the Cisplatin-induced apoptosis and promote chemoresistance in ovarian cancer. PMID- 26826384 TI - Modeling and experimental assessment of a buried Leu-Ile mutation in dengue envelope domain III. AB - Envelope protein domain III (ED3) of the dengue virus is important for both antibody binding and host cell interaction. Here, we focused on how a L387I mutation in the protein core could take place in DEN4 ED3, but cannot be accommodated in DEN3 ED3 without destabilizing its structure. To this end, we modeled a DEN4_L387I structure using the Penultimate Rotamer Library and taking the DEN4 ED3 main-chain as a fixed template. We found that three out of seven Ile(387) conformers fit in DEN4 ED3 without introducing the severe atomic clashes that are observed when DEN3 serotype's ED3 is used as a template. A more extensive search using 273 side-chain rotamers of the residues surrounding Ile(387) confirmed this prediction. In order to assess the prediction, we determined the crystal structure of DEN4_L387I at 2 A resolution. Ile(387) indeed adopted one of the three predicted rotamers. Altogether, this study demonstrates that the effects of single mutations are to a large extent successfully predicted by systematically modeling the side-chain structures of the mutated as well as those of its surrounding residues using fixed main-chain structures and assessing inter-atomic steric clashes. More accurate and reliable predictions require considering sub-angstrom main-chain deformation, which remains a challenging task. PMID- 26826385 TI - Cobalt chloride-mediated protein kinase Calpha (PKCalpha) phosphorylation induces hypoxia-inducible factor 1alpha (HIF1alpha) in the nucleus of gastric cancer cell. AB - Hypoxia promotes cancer progression, and metastasis. The major protein expressed in hypoxic solid cancer is hypoxia-inducible factor 1 (HIF1). We show that enhanced phosphorylation of a conventional protein kinase C isoform, PKCalpha, at threonine 638 (T(638)) by hypoxia-mimetic cobalt chloride induces HIF1alpha in nuclei of gastric epithelial cells (GECs). Moreover, phospho-T(638)-PKCalpha (P PKCalpha) interacts with p300-HIF1alpha complex in the nuclei of hypoxic GECs and PKCalpha phosphorylation at T(638) enhances transcriptional activity of HIF1alpha. High P-PKCalpha expression in neoplastic gastric cancer biopsy samples as compared to nonneoplastic samples suggests that P-PKCalpha might act as an indicator of gastric cancer progression. PMID- 26826386 TI - Two different routes for double-stranded DNA transfer in natural and artificial transformation of Escherichia coli. AB - Escherichia coli is naturally transformable, independent on the conserved DNA uptake machinery for single-stranded DNA (ssDNA) integration. The transfer of double-stranded DNA (dsDNA) during natural transformation of E. coli is regulated by the alternative sigma factor sigma(S). However, it remains mysterious how dsDNA transfers across the membranes and how sigma(S) regulates natural transformation of E. coli. Here, I screened for sigma(S)-regulated genes for dsDNA transfer in E. coli. The screening identified the sigma(S)-regulated genes ydcS and ydcV, both locate on the putative ABC transporter ydcSTUV operon. Considering that ydcS and ydcV are predicted to encode a periplasmic protein and an inner membrane protein for substrate binding and translocation respectively, I propose that they may mediate dsDNA translocation across the inner membrane during natural transformation. In chemical transformation of E. coli, ydcS was but ydcV was not required. Thus, YdcV should not be the channel for dsDNA translocation in artificial transformation. Together with the previous observation that the outer membrane porin OmpA mediates dsDNA transfer across the outer membrane in chemical transformation but not in natural transformation, I conclude that dsDNA transfers across the two membranes through different routes in natural and artificial transformation of E. coli. PMID- 26826387 TI - Plant homologs of mammalian MBT-domain protein-regulated KDM1 histone lysine demethylases do not interact with plant Tudor/PWWP/MBT-domain proteins. AB - Histone lysine demethylases of the LSD1/KDM1 family play important roles in epigenetic regulation of eukaryotic chromatin, and they are conserved between plants and animals. Mammalian LSD1 is thought to be targeted to its substrates, i.e., methylated histones, by an MBT-domain protein SFMBT1 that represents a component of the LSD1-based repressor complex and binds methylated histones. Because MBT-domain proteins are conserved between different organisms, from animals to plants, we examined whether the KDM1-type histone lysine demethylases KDM1C and FLD of Arabidopsis interact with the Arabidopsis Tudor/PWWP/MBT-domain SFMBT1-like proteins SL1, SL2, SL3, and SL4. No such interaction was detected using the bimolecular fluorescence complementation assay in living plant cells. Thus, plants most likely direct their KDM1 chromatin-modifying enzymes to methylated histones of the target chromatin by a mechanism different from that employed by the mammalian cells. PMID- 26826389 TI - MiR-217 is down-regulated in psoriasis and promotes keratinocyte differentiation via targeting GRHL2. AB - MiR-217 is a well-known tumor suppressor, and its down-regulation has been shown in a wide range of solid and leukaemic cancers. However, the biological role of miR-217 in psoriasis pathogenesis, especially in keratinocyte hyperproliferation and differentiation, is not clearly understood. In this study, we found the expression of miR-217 was markedly down-regulated in psoriasis keratinocytes of psoriatic patients. In addition, overexpression of miR-217 inhibited the proliferation and promoted the differentiation of primary human keratinocytes. On the contrary, inhibition of endogenous miR-217 increased cell proliferation and delayed differentiation. Furthermore, Grainyhead-like 2 (GRHL2) was identified as a direct target of miR-217 by luciferase reporter assay. The expression of miR 217 and GRHL2 was inversely correlated in both transfected keratinocytes and in psoriasis lesional skin. Moreover, knocking down GRHL2 expression by siRNA enhanced keratinocyte differentiation. Taken together, our results demonstrate a role for miR-217 in the regulation of keratinocyte differentiation, partially through the regulation of GRHL2. PMID- 26826388 TI - Cloning and characterization of a novel Gladiolus hybridus AFP family gene (GhAFP like) related to corm dormancy. AB - Abscisic acid (ABA) is an important phytohormone controlling seed dormancy. AFPs (ABA INSENSITIVE FIVE BINDING PROTEINS) are reported to be negative regulators of the ABA signaling pathway. The involvement of AFPs in dormant vegetative organs remains poorly understood. Here, we isolated and characterized a novel AFP family member from Gladiolus dormant cormels, GhAFP-like, containing three conserved domains of the AFP family. Quantitative PCR analysis revealed that GhAFP-like was expressed in dormant organs and its expression was down-regulated along with corm storage. GhAFP-like was verified to be a nuclear-localized protein. Overexpressing GhAFP-like in Arabidopsis thaliana not only showed weaker seed dormancy with insensitivity to ABA, but also changed the expression of some ABA related genes. In addition, a primary root elongation assay showed GhAFP-like may involve in auxin signaling response. The results in this study indicate that GhAFP-like acts as a negative regulator in ABA signaling and is related to dormancy. PMID- 26826390 TI - Characterization of actin and tubulin promoters from two sap-sucking pests, Nilaparvata lugens (Stal) and Nephotettix cincticeps (Uhler). AB - The brown planthopper, Nilaparvata lugens (N. lugens, Hemiptera: Delphacidae), and the green rice leafhopper, Nephotettix cincticeps (N. cincticeps, Hemiptera: Cicadellidae), two sap-sucking feeders, have caused many destructive agricultural disasters in East Asia, as they can bring diseases like 'hopper burn' and transmit plant viruses. Recently, continuously-cultured cell lines from both insects have been reported. However, exogenous protein expression systems have not yet been established. Here, we identified thirteen tubulin genes and three actin genes from N. lugens, and one tubulin gene and two actin genes from N. cincticeps. Furthermore, putative promoter regions of these genes were analyzed by bioinformatic approaches and 5'-RACE assay, and the promoter strength was evaluated by driving the enhanced green fluorescent protein expression in three insect cell lines, S2, Sf9, and BmN. Finally, we identified three effective promoters (Nl_alphaTub1 promoter, Nl_act3 promoter, and Nc_act1 promoter) among all candidates we screened. The Nc_act1 promoter showed the strongest activity, while the Nl_alphaTub1 promoter only worked in S2 cells. In conclusion, we identified and functionally characterized three native promoters from N. lugens and N.cincticeps, which would facilitate the establishment of exogenous protein expression systems suitable for these two insect pests. PMID- 26826392 TI - Plants traditionally used as mosquito repellents and the implication for their use in vector control. AB - Numerous plants with insect repelling properties are native to the tropics where they are produced for a wide range of medicinal purposes. In Thailand, these native plant species have a history of use for personal protection against biting insects. From our investigation we identified 37 plant species within 14 plant families that showed some mosquito repellent properties. Of these, 9 plant species were characterized using an excito-repellency test system against several Thai mosquito species. Results from these studies revealed that five essential oils extracted from plants demonstrated promising insect repellent activity. These active ingredients show promise for further development into formulations that may serve as alternatives to DEET or possibly be used as natural bio pesticides to kill mosquitoes. PMID- 26826391 TI - Foraging range of arthropods with veterinary interest: New insights for Afrotropical Culicoides biting midges (Diptera: Ceratopogonidae) using the ring method. AB - The identification of blood meal source of arthropod vector species contributes to the understanding of host-vector-pathogen interactions. The aim of the current work was to identify blood meal source in Culicoides biting midge species, biological vectors of internationally important arboviruses of livestock and equids, using a new ecological approach. We examined the correlation between blood meal source identified in engorged Culicoides females collected in a suction light trap and the available vertebrate hosts along four rings (200, 500, 1000 and 2000 m) centered at the trap site and described the foraging range of the three main vector species of veterinary interest present in the study area, Culicoides imicola, Culicoides kingi and Culicoides oxystoma. The study was performed in four sites localized in the Niayes region of Senegal (West Africa) where recent outbreaks of African horse sickness occurred. Blood meal source identification was carried out by species-specific multiplex PCRs with genomic DNA extracted from the abdomen of engorged females collected during nine night collections for twenty-six collections. The four most abundant hosts present in the studied area (horse, cattle, goat and sheep) were surveyed in each ring zone. The blood meal source varied according to Culicoides species and host availability in each site. C. oxystoma and C. imicola females mainly fed on horses readily available at 200 m maximum from the trap location whereas females of C. kingi fed mainly on cattle, at variable distances from the traps (200 to 2000 m). C. oxystoma may also feed on other vertebrates. We discuss the results in relation with the transmission of Culicoides-borne arboviruses and the species dispersion capacities. PMID- 26826393 TI - 7-aminoclonazepam is superior to clonazepam for detection of clonazepam use in oral fluid by LC-MS/MS. AB - BACKGROUND: Clonazepam (CLON) is not only frequently prescribed in addiction management but is also commonly abused. Therefore many addiction clinics perform oral fluid (OF) testing, which unlike urine is not subject to adulteration, to monitor CLON compliance. However, CLON and other benzodiazepines can be challenging to detect in OF due to their weakly acidic nature and their presence in low concentrations. We determined the optimal technical and clinical approach for the detection of CLON use using OF. METHODS: We measured CLON and its primary metabolite 7-aminoclonazepam (7AC) by liquid chromatography-tandem mass spectrometry in OF specimens over a 2 month period. The samples were collected using the Orasure Intercept OF sample collection device. RESULTS: One hundred samples were presumptive-positive for 7AC and/or CLON. 91 (91.0%) confirmed positive for 7AC (median, range: 4.2, 0.5-316.7 ng/ml) using the ion ratio test, while only 44 of the 100 (44.0%) samples confirmed positive for CLON (median, range: 3.7, 0.5-217.2 ng/ml) using the ion ratio test. In OF the levels of 7AC were approximately 2.4-fold higher than CLON. The use of 7AC as an analyte for the detection of both CLON compliance and undisclosed use is also recommended. CONCLUSIONS: 7AC should be the analyte measured in OF for the detection of CLON use. PMID- 26826394 TI - D-dimer as a potential biomarker for the progression of COPD. AB - BACKGROUND: D-dimer is a manifestation of endogenous fibrinolytic activity and associated with inflammation process. Despite chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by a hypercoagulable state, D-dimer levels in COPD patients are still conflicting. METHODS: Forty-three participants were investigated at admission for an acute exacerbation of COPD, and reassessed when stable. Forty-three controls were matched for age, gender, body mass index, smoking index, comorbidities and medication use. Participants underwent pulmonary function and laboratory testing, including the measurements of D-dimer and high-sensitivity C-reactive protein (hsCRP). RESULTS: The median of D-dimer was 2839 MUg/l (IQR: 2078-4389 MUg/l) and 1799 MUg/l (IQR: 1205-2196 MUg/l) in exacerbated and stable COPD patients respectively. The median of D-dimer in the control subjects was 433 MUg/l (IQR: 369-456 MUg/l). D-dimer level was significantly increased in stable COPD patients compared with healthy controls, and further increased in those patients with an acute exacerbation (both P<0.001). D-dimer was positively correlated with the well-known inflammatory marker hsCRP both in the exacerbated and stable phases of COPD (r=0.392 P=0.009 and r=0.411 P=0.006, respectively), and negatively correlated with FEV1% predicted and FEV1/FVC in stable COPD (r=-0.409 P=0.006 and r=-0.343 P=0.024, respectively). CONCLUSIONS: D-dimer is increased in COPD patients, and could be considered as an inflammatory marker for the assessment of inflammation in the progression of COPD. PMID- 26826395 TI - Platelet proteomics in diagnostic differentiation of primary immune thrombocytopenia using SELDI-TOF-MS. AB - BACKGROUND: Primary immune thrombocytopenic purpura (pITP) is defined as isolated autoimmune thrombocytopenia with idiopathic low platelet count, normal bone marrow, and unexplained causes of thrombocytopenia. Currently there is no definite criterion for ITP diagnosis. METHODS: We conducted proteomic screen of patients with pITP, secondary immune thrombocytopenia (sITP), and healthy controls using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). The proteomic profiles were obtained from platelet lysate samples of 82 healthy adult controls, 64 pITP, and 70 sITP patients, from which we screened marker proteins with significant differences, and constructed a diagnosis model using the artificial neural network (ANN) technique. RESULTS: We identified 6 marker proteins in the platelet lysates of pITP patients. This diagnosis method differentiated pITP patients from sITP effectively with a sensitivity of 96.9% (31/32), a specificity of 71.0% (54/76), and the area under the ROC curve of 0.864 in the training set, and a sensitivity of 87.5% (28/32), a specificity of 69.7% (53/76), and a positive predictive value of 75.0% (81/108) in the test set. CONCLUSION: The artificial neural network model based on platelet protein profiling established a potential pITP diagnosis platform. PMID- 26826396 TI - Circulating TGF-beta1 levels are negatively correlated with sclerostin levels in early postmenopausal women. AB - BACKGROUND: TGF-beta1 regulates bone metabolism and mediates bone turnover during postmenopause. Sclerostin negatively regulates Wnt signaling pathway and also has an important role in postmenopausal bone loss. Little is known about the relationship between serum TGF-beta1 and sclerostin during menopause. METHODS: We compared serum levels of TGF-beta1 and sclerostin in pre- and postmenopausal women and assessed the potential correlations of these levels with each other and with serum levels of bone turnover markers and bone mineral density. RESULTS: A total of 176 women (58 premenopausal, 62 early postmenopausal, and 56 late postmenopausal) were included in this study. Serum TGF-beta1 level was significantly higher in early postmenopausal women compared with premenopausal (32.0+/-7.19 vs. 26.55+/-6.67 ng/ml, p=0.01) and late postmenopausal (32.0+/-7.19 vs. 28.65+/-7.70 pg/ml, p=0.031) women, and no significant differences in serum sclerostin levels were observed among the 3 groups. There was a significant negative correlation between TGF-beta1 and sclerostin in early postmenopausal women, but not in other groups of women. Based on multiple regression analysis, only TGF-beta1 (beta=-0.362; p=0.007) was an independent predictor of sclerostin during early postmenopause. CONCLUSIONS: Our findings suggest that serum TGF beta1 level increases during postmenopause and declines in old age. Sclerostin production is inhibited by TGF-beta1 during early postmenopause. PMID- 26826397 TI - Hormonal Physiology of Childbearing, an Essential Framework for Maternal-Newborn Nursing. AB - Knowledge of the hormonal physiology of childbearing is foundational for all who care for childbearing women and newborns. When promoted, supported, and protected, innate, hormonally driven processes optimize labor and birth, maternal and newborn transitions, breastfeeding, and mother-infant attachment. Many common perinatal interventions can interfere with or limit hormonal processes and have other unintended effects. Such interventions should only be used when clearly indicated. High-quality care incorporates salutogenic nursing practices that support physiologic processes and maternal-newborn health. PMID- 26826398 TI - Pharmacological inhibitors of autophagy as novel cancer therapeutic agents. AB - Autophagy is an evolutionarily conserved cellular degradative process in which intracellular components (cellular proteins and organelles) are engulfed in autophagosomes which then fuse with lysosomes to form autolysosome for degradation. Autophagy is closely implicated in various physio-pathological processes and human diseases. Among them, the roles of autophagy in cancer have been extensively studied. Increasing evidence has demonstrated that inhibiting autophagy is a novel and promising approach in cancer therapy, based on the notion that autophagy is a pro-survival mechanism in cancer cells under therapeutic stress, and induction of autophagy is associated with chemoresistance of cancer cells to chemotherapeutic agents. Thus, suppression of autophagy would sensitize resistance tumor cells to cancer therapeutic agents, thereby supporting the clinical application of autophagy inhibitors. In recent years, significant progress has been achieved in developing autophagy inhibitors and testing their therapeutical potential, either as standalone or as adjuvant therapeutic agents, in cell and animal models, and more importantly in clinical trials. In this review, we will discuss some of these recent advances in development of novel small molecules autophagy inhibitors and their mechanisms of action, together with their applications in clinical trials. PMID- 26826399 TI - Cognitive enhancers versus addictive psychostimulants: The good and bad side of dopamine on prefrontal cortical circuits. AB - In this review we describe how highly addictive psychostimulants such as cocaine and methamphetamine actions might underlie hypoexcitabilty in frontal cortical areas observed in clinical and preclinical models of psychostimulant abuse. We discuss new mechanisms that describe how increments on synaptic dopamine release are linked to reduce calcium influx in both pre and postsynaptic compartments on medial PFC networks, therefore modulating synaptic integration and information. Sustained DA neuromodulation by addictive psychostimulants can "lock" frontal cortical networks in deficient states. On the other hand, other psychostimulants such as modafinil and methylphenidate are considered pharmacological neuroenhancement agents that are popular among healthy people seeking neuroenhancement. More clinical and preclinical research is needed to further clarify mechanisms of actions and physiological effects of cognitive enhancers which show an opposite pattern compared to chronic effect of addictive psychostimulants: they appear to increase cortical excitability. In conclusion, studies summarized here suggest that there is frontal cortex hypoactivity and deficient inhibitory control in drug-addicted individuals. Thus, additional research on physiological effects of cognitive enhancers like modafinil and methylphenidate seems necessary in order to expand current knowledge on mechanisms behind their therapeutic role in the treatment of addiction and other neuropsychiatric disorders. PMID- 26826401 TI - The application of terahertz pulsed imaging in characterising density distribution of roll-compacted ribbons. AB - Roll compaction is a commonly used dry granulation process in pharmaceutical, fine chemical and agrochemical industries for materials sensitive to heat or moisture. The ribbon density distribution plays an important role in controlling properties of granules (e.g. granule size distribution, porosity and strength). Accurate characterisation of ribbon density distribution is critical in process control and quality assurance. The terahertz imaging system has a great application potential in achieving this as the terahertz radiation has the ability to penetrate most of the pharmaceutical excipients and the refractive index reflects variations in density and chemical compositions. The aim of this study is to explore whether terahertz pulse imaging is a feasible technique for quantifying ribbon density distribution. Ribbons were made of two grades of microcrystalline cellulose (MCC), Avicel PH102 and DG, using a roll compactor at various process conditions and the ribbon density variation was investigated using terahertz imaging and section methods. The density variations obtained from both methods were compared to explore the reliability and accuracy of the terahertz imaging system. An average refractive index is calculated from the refractive index values in the frequency range between 0.5 and 1.5THz. It is shown that the refractive index gradually decreases from the middle of the ribbon towards to the edges. Variations of density distribution across the width of the ribbons are also obtained using both the section method and the terahertz imaging system. It is found that the terahertz imaging results are in excellent agreement with that obtained using the section method, demonstrating that terahertz imaging is a feasible and rapid tool to characterise ribbon density distributions. PMID- 26826400 TI - Conditioned cortical reactivity to cues predicting cigarette-related or pleasant images. AB - Through Pavlovian conditioning, reward-associated neutral stimuli can acquire incentive salience and motivate complex behaviors. In smokers, cigarette associated cues may induce cravings and trigger smoking. Understanding the brain mechanisms underlying conditioned responses to cigarette-associated relative to other inherently pleasant stimuli might contribute to the development of more effective smoking cessation treatments that emphasize the rehabilitation of reward circuitry. Here we measured brain responses to geometric patterns (the conditioned stimuli, CSs) predicting cigarette-related, intrinsically pleasant and neutral images (the unconditioned stimuli, USs) using event-related potentials (ERPs) in 29 never-smokers, 20 nicotine-deprived smokers, and 19 non deprived smokers. Results showed that during US presentation, cigarette-related and pleasant images prompted higher cortical positivity than neutral images over centro-parietal sensors between 400 and 800ms post-US onset (late positive potential, LPP). The LPP evoked by pleasant images was significantly larger than the LPP evoked by cigarette images. During CS presentation, ERPs evoked by geometric patterns predicting pleasant and cigarette-related images had significantly larger amplitude than ERPs evoked by CSs predicting neutral images. These effects were maximal over right parietal sites between 220 and 240ms post CS onset and over occipital and frontal sites between 308 and 344ms post-CS onset. Smoking status did not modulate these effects. Our results show that stimuli with no intrinsic reward value (e.g., geometric patterns) may acquire rewarding properties through repeated pairings with established reward cues (i.e., cigarette-related, intrinsically pleasant). PMID- 26826402 TI - Importance of universal mismatch repair protein immunohistochemistry in patients with sebaceous neoplasia as an initial screening tool for Muir-Torre syndrome. AB - Muir-Torre syndrome, a Lynch syndrome variant, is characterized by sebaceous neoplasia plus one or more malignancies, typically colon cancer. The significance of DNA mismatch repair (MMR) deficiency detection by immunohistochemistry (IHC) in colorectal carcinomas is well established and is recommended as a screening tool for Lynch syndrome in newly diagnosed colorectal carcinomas. In comparison, literature on IHC application to detect MMR proteins (MLH1, MSH2, MSH6, and PMS2) in sebaceous neoplasia has been less studied and has been derived almost exclusively from tertiary care centers. Herein we describe the largest series to date characterizing MMR deficiency in sebaceous neoplasms, as well as the relative frequencies of each deficiency. Two hundred sixteen consecutive sebaceous neoplasms (216 patients) were analyzed from a community practice setting (133 sebaceous adenomas, 68 sebaceomas, 15 sebaceous carcinomas). One hundred forty-three were MMR deficient (66%), of which 90 were MSH2/MSH6 deficient (63%), 27 MLH1/PMS2 deficient (19%), 22 MSH6 deficient (15%), and 4 PMS2 deficient (3%). MMR deficiency was significantly associated with site, with tumors off of the head and neck more likely to be MMR deficient (specificity 96%). In contrast to prior reports, no significant trend in MMR-deficient versus nondeficient tumors was seen in age at presentation (median age, 68 versus 66), tumor-infiltrating lymphocytes, or tumor type. Given the low sensitivity of age < 60 years (30%), location off of the head and neck (41%), or presence of tumor infiltrating lymphocytes (29%) in MMR deficiency detection, IHC screening programs should test all sebaceous neoplasms for MMR deficiency, regardless of their clinicopathological features. PMID- 26826403 TI - Should the involvement of skeletal muscle by prostatic adenocarcinoma be reported on biopsies? AB - Skeletal muscle is seen at the distal part of the prostate apex, where benign glands may reside as part of normal anatomy and histology, and extends more proximally anteriorly. At times, prostatic adenocarcinoma can be seen admixed with skeletal muscle, raising the question of extraprostatic extension. Although there has been increased attention regarding biopsy sampling of the distal apex to guide the performing of the apical dissection on radical prostatectomy, the finding of skeletal muscle involvement by prostatic adenocarcinoma has not been consistently reported by pathologists on biopsies. We searched our database spanning 12 years from 2000 to 2012 for all patients who had prostatic adenocarcinoma Gleason score 3 + 3 = 6 involving skeletal muscle on biopsy. We identified 220 patients who met the criteria. Of the 220 patients, 101 underwent prostatectomy, which comprised the "study group." Prostatectomy reports from these patients were compared with those of a "control group," which consisted of 201 contemporaneous patients with Gleason score 3 + 3 = 6 prostatic adenocarcinoma on biopsy without skeletal muscle involvement. The results showed a significantly higher percentage of positive margins in the study group compared with the control group (P = .006). The study group also had a higher percentage of positive margins at the apex admixed with skeletal muscle (P = .008). In summary, the findings in this study support that pathologists should report the involvement of skeletal muscle by tumor, and recommend that urologists performing radical prostatectomies on these patients try to ensure adequate excision in the apical area to avoid positive apical margin. PMID- 26826404 TI - Cytokeratin-positive interstitial reticulum cell tumor: recognition of a potential "in situ" pattern. AB - Cytokeratin-positive interstitial reticulum cell (CIRC) tumor is a very rare accessory cell neoplasm of lymphoid organs derived from fibroblastic reticulum cells, which originate from mesenchymal stem cells. We describe the histologic, immunophenotypical, and molecular features of a CIRC tumor in a 67-year-old woman who underwent hysterectomy, bilateral adnexectomy, and pelvic lymphadenectomy for endometrial carcinoma. An enlarged pelvic node contained circumscribed neoplastic infiltrates in perifollicular and interfollicular areas consisting of large cells arranged in a reticular pattern with nuclear atypia, atypical mitoses, and apoptosis, but without glandular architecture or disruption of overall architecture. The atypical infiltrate coexpressed cytokeratin and vimentin, partially CD68, CD163, and lysozyme, but lacked markers of endometrial carcinoma, consistent with a diagnosis of CIRC tumor. Despite the obviously neoplastic cytological features, immunostains revealed the circumscribed and noninvasive pattern of the lesion, possibly representing an early "in situ" stage of CIRC tumor. PMID- 26826405 TI - Ciliated muconodular papillary tumor: a solitary peripheral lung nodule in a teenage girl. AB - Papillary tumors of the peripheral lung containing ciliated cells and extracellular mucin include solitary peripheral ciliated glandular papilloma, ciliated muconodular papillary tumor, and well-differentiated papillary adenocarcinoma with cilia formation. We report the case of a 19-year-old woman who was a nonsmoker and presented with an incidental small peripheral lung nodule. The resection specimen showed a soft grayish nodule. Histologic examination further revealed a relatively circumscribed mucinous nodule featuring a tubulopapillary tumor composed of ciliated columnar cells and goblet cells, accompanied with abundant extracellular mucin. No lepidic growth pattern was evident. The tumor cells were immunoreactive for cytokeratin 7, thyroid transcription factor-1, and carcinoembryonic antigen, whereas p63 and cytokeratin 5/6 highlighted the presence of basal cells. Next-generation sequencing did not identify any genetic alterations in targeted regions and mutational hotspots of a panel of 22 genes commonly implicated in lung and colon cancers. Taken together, our case was most likely a ciliated muconodular papillary tumor. PMID- 26826406 TI - Neonatal multiorgan failure due to ACAD9 mutation and complex I deficiency with mitochondrial hyperplasia in liver, cardiac myocytes, skeletal muscle, and renal tubules. AB - Complex I deficiency causes Leigh syndrome, fatal infant lactic acidosis, and neonatal cardiomyopathy. Mutations in more than 100 nuclear DNA and mitochondrial DNA genes miscode for complex I subunits or assembly factors. ACAD9 is an acyl CoA dehydrogenase with a novel function in assembly of complex I; biallelic mutations cause progressive encephalomyopathy, recurrent Reye syndrome, and fatal cardiomyopathy. We describe the first autopsy in fatal neonatal lethal lactic acidosis due to mutations in ACAD9 that reduced complex I activity. We identified mitochondrial hyperplasia in cardiac myocytes, diaphragm muscle, and liver and renal tubules in formalin-fixed, paraffin-embedded tissue using immunohistochemistry for mitochondrial antigens. Whole-exome sequencing revealed compound heterozygous variants in the ACAD9 gene: c.187G>T (p.E63*) and c.941T>C (p.L314P). The nonsense mutation causes late infantile lethality; the missense variant is novel. Autopsy-derived fibroblasts had reduced complex I activity (53% of control) with normal activity in complexes II to IV, similar to reported cases of ACAD9 deficiency. PMID- 26826407 TI - Mucocele-like lesions of the breast: a clinical outcome and histologic analysis of 102 cases. AB - Mucocele-like lesions (MLLs) of the breast are characterized by cystic architecture with stromal mucin and frequent atypia, but it is unknown whether they convey long-term breast cancer risk. We evaluated 102 MLLs that were derived from a single-institution benign breast disease cohort of 13412 women who underwent biopsy from 1967 to 2001. MLLs were histologically characterized by type of lining epithelium, architecture of the lesion, associated atypical hyperplasia (AH), and incidence of breast cancer (14.8-year median follow-up). A relatively large proportion of MLLs (42%) were diagnosed in women older than 55 years. AH was significantly more frequent in MLL patient compared to the cohort overall (27% versus 5%; P < .001). Breast cancer has developed in 13 patients with MLL. This frequency is only slightly higher than population expected rates overall (standardized incidence ratio, 2.28; 95% confidence interval, 1.21-3.91) and not significantly different from women in the cohort with (nonatypical) proliferative breast lesions. Younger women (<45) with MLL had a nonsignificant increase in risk of cancer compared to the general population (standardized incidence ratio, 5.16; 95% confidence interval, 1.41-13.23). We conclude that MLL is an uncommon breast lesion that is often associated with coexisting AH. However, in women older than 45 years, MLLs do not convey additional risk of breast cancer beyond that associated with the presence of proliferative disease. PMID- 26826408 TI - Morphologic characterization of hamartomatous gastrointestinal polyps in Cowden syndrome, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. AB - The morphologic features of the gastrointestinal polyps in hamartomatous polyposis syndromes are poorly defined. Our aim was to better characterize the gastrointestinal hamartomas in these syndromes. A blinded review was performed regarding many histologic features for every polyp. The study included 15 Cowden syndrome, 13 Peutz-Jeghers (PJS), 12 juvenile polyposis (JuvPS) patients, and 32 cases of sporadic hamartomatous polyps. A total of 375 polyps were examined. Cowden syndrome polyps were characteristically colonic, sessile, small, without surface erosion, and showing mildly inflamed fibrotic lamina propria with smooth muscle proliferation and lymphoid follicles. They showed the least degree of cystic glands and had no thick mucin. Uncommon but specific features were ganglion cells and nerve fibers within the lamina propria and mucosal fat. PJS polyps were typically of small or large bowel origin, often exophytic, seldom eroded, with inflamed edematous and fibrotic lamina propria and dilated cystic glands filled with often thick mucin. All PJS polyps showed smooth muscle proliferation, frequently widespread. The polyps of JuvPS were typically colonic, large, exophytic, eroded, with strikingly edematous, fibrotic markedly inflamed lamina propria, cystic glands filled with frequently thick mucin, and the least degree of smooth muscle proliferation. Nonsyndromic hamartomatous polyps were similar to JuvPS polyps; however, they were more often colonic, were smaller, showed more widespread smooth muscle proliferation, and were less likely to contain thick mucin. In conclusion, we were able to define the characteristic hamartomatous polyp for each hamartomatous polyposis syndrome. Awareness to these features may aid in the diagnosis of these rare syndromes. PMID- 26826409 TI - CXCR4 overexpression correlates with poor prognosis in myasthenia gravis associated thymoma. AB - Thymoma is 1 rare type of tumor developed on the thymic epithelium; patients with thymoma also might have myasthenia gravis (MG). Because of the scarcity and complexity of MG-associated thymoma, its pathogenesis and etiology still remain unclear nowadays. The expression of C-X-C chemokine receptor type 4 (CXCR4) is absent or low in most healthy tissues but highly expressed in various types of tumors. Here, to determine the prognostic significance of CXCR4 in MG-associated thymoma, a total of 84 tissue samples were retrospectively examined. Our data demonstrated that CXCR4 was strongly associated with worse overall survival (hazard ratio, 2.11; 95% confidence interval, 1.08-4.11) and disease-free survival (hazard ratio, 1.84; 95% confidence interval, 1.03-3.29). Furthermore, both univariate and multivariate analyses confirmed that CXCR4 was an independent factor in predicting unfavorable overall survival. In conclusion, our findings suggest that CXCR4 might contribute to the clinical cancer progression, and CXCR4 could be a valuable prognostic biomarker in the therapy of MG-associated thymoma. PMID- 26826410 TI - Chromosome 12p abnormalities and IMP3 expression in prepubertal pure testicular teratomas. AB - Although the histologic appearance of pure testicular teratomas (PTTs) is similar in children and adults, the prognosis is dramatically different. Prepubertal PTTs are rare, with a benign clinical course, whereas the adult cases typically have malignant outcomes. Chromosome 12p abnormalities are seen in most adult testicular germ cell tumors but have not been found in prepubertal PTTs. IMP3 is an oncofetal protein that is highly expressed in many malignancies. Recently, we demonstrated IMP3 is expressed in adult mature testicular teratomas but not in mature ovarian teratomas. The aim of this study was to evaluate prepubertal PTTs for chromosome 12p abnormalities and expression of IMP3. A total of 11 cases (excision, n=1; orchiectomy, n=10) were obtained from the surgical pathology archives of 2 large medical centers (1957-2013). All 11 cases were investigated for isochromosome 12p and 12p copy number gain using interphase fluorescence in situ hybridization analysis and were examined by immunohistochemistry for IMP3 expression. Patients ranged in age from 0.9 to 7.0 (mean, 2.4) years. A positive immunohistochemical stain for IMP3 (cytoplasmic staining) was identified in 5 (46%) of 11 cases. Isochromosome 12p was detected in 2 cases (18%) that also expressed IMP3. Somatic copy number alterations of 12p were not observed (0%). We are the first to describe 12p abnormalities and IMP3 expression in prepubertal PTTs. Our data demonstrate a small subset of PTTs harbor typical molecular alterations observed in adult testicular germ cell tumors. Although prepubertal PTTs are considered to be benign neoplasms, it may be a heterogeneous group. PMID- 26826411 TI - Various ARID1A expression patterns and their clinical significance in gastric cancers. AB - AT-rich interactive domain 1A (ARID1A) is frequently mutated in gastric cancers, and loss of ARID1A expression is considered a poor prognostic factor in various cancers. However, in practice, ARID1A shows various expression patterns, and our understanding of its significance is limited. We performed immunohistochemistry for ARID1A, MLH1, and pS6 using whole tissue blocks of 350 gastric cancers and classified the ARID1A expression as follows: retained (63.7%), reduced (17.7%), complete loss (14.9%), and partial loss (3.7%). Complete/partial loss was more common in poorly differentiated histology (P < .001), and reduced or complete loss of ARID1A was frequent in cases with MLH1 loss (P < .001). The ARID1A reduced group showed only slightly inferior disease-free survival (DFS; P = .254) and overall survival (OS; P = .377) compared to those of the ARID1A-retained group, whereas the group with complete loss showed significantly worse DFS (hazard ratio [HR], 1.732; P = .015) and OS (HR, 1.751; P = .013). Worse DFS (HR, 2.672; P = .005) and OS (HR, 2.531; P = .002) were also noted in the group with partial loss. High expression of pS6 was observed more frequently in groups showing altered ARID1A expression patterns (P < .001). In conclusion, reduced ARID1A expression is not a major prognostic determinant, although it may lead to AKT pathway activation. Tumor cells lacking ARID1A expression may influence the prognosis even if they constitute only a small proportion of the tumor sample. Our data provide an enhanced roadmap for understanding ARID1A with implications for future research and therapeutics. PMID- 26826412 TI - Ectopic primary intrathyroidal thymoma: a clinicopathological and immunohistochemical analysis of 3 cases. AB - Thymomas are rare tumors that occasionally arise from ectopic locations. Ectopic thymomas originating within the thyroid gland are an exceedingly uncommon clinical entity that has only been described sporadically. In this study, we present the clinicopathological and immunohistochemical features of 3 primary intrathyroidal thymomas. The patients were 2 women and 1 man between the ages of 43 and 53 years (average, 48 years). Clinically, the patients presented with neck pain or enlarged thyroid glands. Physical examination and thyroid ultrasound revealed the presence of nodular masses confined to the thyroid parenchyma. No concurrent mediastinal tumors were identified in any of the cases, and none of the patients had a history of thymoma. Fine needle aspirate performed in 1 case was interpreted as possibly Hashimoto thyroiditis. Surgical resection was performed in all cases. Grossly, the lesions were circumscribed masses measuring from 1 to 4 cm in size. Histologically, the lesions showed the classic biphasic cellular proliferation of thymomas characterized by varying proportions of epithelial cells and lymphocytes. Two patients remain alive and well 1.5 to 2 years after their surgical resection, whereas the third patient was lost to follow-up. The cases herein presented highlight an unusual tumor entity that can be clinically confused for more common lesions affecting the thyroid gland. Awareness of this entity is important to avoid misdiagnosis and secure appropriate clinical management. PMID- 26826413 TI - Expression of store-operated channel components in prostate cancer: the prognostic paradox. AB - In vitro studies in prostate cancer (PCa) cell lines have suggested a key and complex role of the store-operated channels (SOCs) in major cancer hallmarks, including proliferation, apoptosis, and migration. In the present study, we investigated in vivo the expression of the SOC components transient receptor potential canonical (TRPC) 1, TRPC4, Orai1, and stromal interaction molecule 1 (STIM1), during all stages of PCa progression, and evaluated their prognostic impact in clinically localized cancer (CLC). The expressions of TRPC1, TRPC4, Orai1, STIM1, and the androgen receptor and the proliferation marker Ki-67 were evaluated by immunohistochemistry on tissue microarrays containing samples of normal prostate tissues (n=91), prostatic intraepithelial neoplasia (n=61), CLC surgically treated (n=238), and castration-resistant prostate cancer (CRPC; n=45). All markers significantly increased in CLC compared with normal tissues and (for Orai1 and STIM1) in advanced pT3 tumors compared with pT2. In contrast, their expression decreased in CRPC, particularly for Orai1. In CLC, staining for TRPC1, Orai1 and STIM1 correlated with androgen receptor expression, and TRPC1 status was associated with lower proliferation and longer recurrence-free survival, after adjusting for classical prognostic markers. Although increased SOC expression during PCa progression supports a role in cancer cell migration, the inverse association between TRPC1 and biochemical relapse suggests a protective effect in CLC. Moreover, the dramatic down-regulation of Orai1 in CRPC supports its role in apoptosis at this stage of the disease. These results call for caution when considering SOCs as potential therapeutic targets for PCa. PMID- 26826414 TI - Renal cell carcinoma with vena caval involvement: a contemporary clinicopathologic analysis of 53 cases. AB - A clinicopathologic analysis of patients with renal cell carcinoma (RCC) and vena caval involvement diagnosed at our institution was performed. Multiple clinicopathologic parameters were examined. Fifty-three cases were identified. Mean patient age was 62 years (range, 40-82 years). The cohort comprised 36 of 53 (68%) men and 17 of 53 (32%) women. Mean primary tumor size was 10.4 cm (range, 3.1-21.0 cm). The breakdown of tumor stage was as follows: 37 of 53 (70%) were pT3b, 14 of 53 (26%) were pT3c, and 2 of 53 (4%) were pT4. Most of the tumors were clear cell RCC (45/53, 84.6%), although other variants were also represented. All cases were Fuhrman nuclear grade 3 (34/53, 64%) or 4 (19/53, 36%). Tumor necrosis was present in 41 of 53 (77%) cases. At the time of the initial tumor resection, 11 of 53 (21%) cases were staged pM1. Of the 42 patients staged as pMX at the time of primary tumor resection, 12 of 42 (29%) later developed metastasis, most commonly to the lungs. Of all 53 cases with these very advanced tumors, only 6 of 53 (11.3%) had positive surgical margins: 4 of 53 (7.5%) had positive vascular resection margins, and 2 of 53 (3.8%) had focally positive perinephric fat margins. The mean 5-year survival in our cohort was 50%. Our findings suggest that a select group of patients with RCC with vena caval involvement may benefit from radical nephrectomy, although some tumors may have positive vascular and/or nonvascular surgical resection margins even in the best surgical hands. Multi-institutional studies are needed to further characterize these advanced tumors from the molecular standpoint. PMID- 26826415 TI - Phosphohistone H3 expression correlates with manual mitotic counts and aids in identification of "hot spots" in fibroepithelial tumors of the breast. AB - Classification of mammary fibroepithelial tumors (FETs) relies on assessment of mitotic activity, among other histopathologic parameters. Routine hematoxylin and eosin (H&E) mitotic counts can be subjective and time consuming. Difficulty may arise in identifying "true" mitoses for a variety of reasons. Phosphorylation of histone H3 protein (PHH3) is correlated with mitotic chromatin condensation. The utility of PHH3 immunohistochemical staining to identify mitoses has been demonstrated in multiple organ systems. In this study, we examined the utility of PHH3 in assessing mitotic activity in FETs and compared PHH3- with H&E-determined mitotic counts. PHH3-stained mitoses were readily identifiable at *10 magnification and allowed for rapid identification of mitotic "hot spots." Median mitotic counts/10 high-power fields for fibroadenoma, benign phyllodes tumor, borderline phyllodes tumor (BlnPT), and malignant phyllodes tumor (MPT) were 0, 0.5, 4.25, and 9, respectively on H&E, and 0, 0.75, 4.5, and 8, respectively for PHH3. Among all FETs, there was a strong positive correlation between H&E- and PHH3-determined mitotic counts (r=0.91, P<.001). Using PHH3, 2 cases would be reclassified, both from BlnPT to MPT. PHH3-determined counts correlated with H&E determined counts in FETs. Using PHH3, a small number of cases were reclassified from BlnPT to MPT, for which treatment is similar. Although H&E-determined counts remain the criterion standard for assessing mitotic activity in FETs, PHH3 may be a useful adjunctive tool in some cases and is helpful in identifying mitotic hot spots. PMID- 26826416 TI - Histomolecular profiling of pleomorphic, spindle cell, and giant cell carcinoma of the lung for targeted therapies. AB - In pleomorphic, spindle cell, and giant cell carcinoma (PSCGC) of the lung, we wondered if an integrated diagnosis including morphological and immunohistochemical features could be related to molecular status. We performed immunohistochemistry on 35 PSCGCs against TTF1, napsin A, p40, ALK, ROS1, and c MET. Mutational status regarding EGFR, KRAS, BRAF, HER2, and PIK3CA genes was established. Of 18 PSCGCs with adenocarcinomatous or "undifferentiated" carcinoma differentiation, 8 were mutated for EGFR (n = 1), KRAS (n = 2), BRAF (n = 1), HER2 (n = 3), and PIK3CA (n = 1). No PSCGC (0/4) with only squamous cell or adenosquamous (0/2) differentiation was mutated. c-MET overexpression was only seen in PSCGC with adenocarcinomatous or undifferentiated component (n = 5) without squamous cell component. ROS1 and ALK were negative. The presence of a "targetable mutation" was correlated to the presence of morphological or immunohistochemical adenocarcinomatous differentiation (P = .0137). Integrated diagnosis of an adenocarcinomatous component in PSCGC could be associated with the presence of targetable gene mutation. Because only PSCGC with adenocarcinomatous or undifferentiated carcinoma harbors mutations, whereas PSCGC with only squamous or adenosquamous differentiation does not in our study, this might represent a prescreening for patients with PSCGC to be tested for molecular targets. Our results emphasize that careful morphological examination and the use of immunohistochemistry might be useful for the selection of PSCGC tested for a mutational target. PMID- 26826417 TI - Intramedullary gangliogliomas: histopathologic and molecular features of 25 cases. AB - Gangliogliomas are uncommon glioneuronal tumors, which usually arise in the cerebral hemispheres and occasionally in the brain stem. Gangliogliomas occurring in the spinal cord are extremely rare. In this study, we analyzed the clinical, histopathologic, and molecular features of 25 spinal gangliogliomas. The cases included in our series affected mostly children and young adults (15 males and 10 females; mean age, 20 years; median age, 14 years; age range, 1-72 years) and were predominantly localized in the cervical and thoracic spine. From the clinical point of view (detailed follow-up available for 9 pediatric cases; mean follow-up: 2 years 10 months; range, 3 months to 5 years 10 months), most patients showed stable disease after subtotal resection. Radiotherapy was rarely used as adjuvant treatment. Histologically, gangliogliomas (WHO grade I) (21 cases) showed features largely similar to their supratentorial counterparts. Anaplastic gangliogliomas (World Health Organization grade III) (4 cases) showed features of anaplasia (including high cellularity and increased mitotic and proliferation activity). From a molecular point of view, only 2 tumors (2/19, 11%) harbored a BRAF(V600E) mutation. In conclusion, although spinal gangliogliomas display histologic and clinical features similar to their supratentorial counterparts, they show a relatively low frequency of BRAF(V600E) mutations, alteration otherwise common in hemispheric and brain stem gangliogliomas. PMID- 26826418 TI - Ductal carcinoma in situ of the breast: the importance of morphologic and molecular interactions. AB - Ductal carcinoma in situ (DCIS) of the breast is a lesion characterized by significant heterogeneity, in terms of morphology, immunohistochemical staining, molecular signatures, and clinical expression. For some patients, surgical excision provides adequate treatment, but a subset of patients will experience recurrence of DCIS or progression to invasive ductal carcinoma (IDC). Recent years have seen extensive research aimed at identifying the molecular events that characterize the transition from normal epithelium to DCIS and IDC. Tumor epithelial cells, myoepithelial cells, and stromal cells undergo alterations in gene expression, which are most important in the early stages of breast carcinogenesis. Epigenetic modifications, such as DNA methylation, together with microRNA alterations, play a major role in these genetic events. In addition, tumor proliferation and invasion is facilitated by the lesional microenvironment, which includes stromal fibroblasts and macrophages that secrete growth factors and angiogenesis-promoting substances. Characterization of DCIS on a molecular level may better account for the heterogeneity of these lesions and how this manifests as differences in patient outcome and response to therapy. Molecular assays originally developed for assessing likelihood of recurrence in IDC are recently being applied to DCIS, with promising results. In the future, the classification of DCIS will likely incorporate molecular findings along with histologic and immunohistochemical features, allowing for personalized prognostic information and therapeutic options for patients with DCIS. This review summarizes current data regarding the molecular characterization of DCIS and discusses the potential clinical relevance. PMID- 26826419 TI - Colorectal poorly differentiated neuroendocrine carcinomas frequently exhibit BRAF mutations and are associated with poor overall survival. AB - The molecular alterations in colorectal poorly differentiated neuroendocrine carcinoma remain incompletely characterized, particularly with respect to mutations in BRAF and KRAS. We analyzed 32 colorectal poorly differentiated neuroendocrine carcinomas and 40 colorectal poorly differentiated conventional adenocarcinomas for mutations in KRAS and BRAF and for DNA mismatch repair protein abnormalities to correlate histopathology with molecular alterations and survival. Compared with poorly differentiated conventional adenocarcinoma, poorly differentiated neuroendocrine carcinoma frequently harbored BRAF mutations (59% versus 5%; P < .001) and less frequently demonstrated KRAS codon 12 or 13 mutations (17% versus 43%; P = .03). BRAF mutations were identified in both pure poorly differentiated neuroendocrine carcinoma (60%) and poorly differentiated neuroendocrine carcinoma associated with a signet ring cell adenocarcinoma component (82%). Most (93%) poorly differentiated neuroendocrine carcinomas demonstrated proficient DNA mismatch repair by either microsatellite instability polymerase chain reaction or DNA mismatch repair immunohistochemistry. Patients with poorly differentiated neuroendocrine carcinoma had a significantly worse overall survival compared with patients with poorly differentiated conventional adenocarcinoma (P < .001). There was no significant difference in overall survival between patients with pure poorly differentiated neuroendocrine carcinoma and patients with both poorly differentiated neuroendocrine carcinoma and adenocarcinoma components (P = .5). In conclusion, colorectal poorly differentiated neuroendocrine carcinomas frequently harbor BRAF mutations and are associated with poor overall survival. PMID- 26826420 TI - Endothelial cell injury in acute and chronic glomerular lesions in patients with IgA nephropathy. AB - Endothelial cell injury may contribute to the progression of various glomerular diseases. In the present study, we examined glomerular capillary injury in acute and chronic glomerular lesions in patients with Immunoglobulin A nephropathy (IgAN). We selected renal biopsy samples of IgAN (n = 200), and glomerular capillary injury in the acute and chronic glomerular lesions was assessed using immunohistochemistry for CD34 and electron microscopy. We examined the correlations between acute and chronic glomerular lesions and proteinuria, hematuria, and the renal function. The injured glomerular capillaries in the acute glomerular lesions were characterized morphologically by the separation of CD34+ endothelial cells from the glomerular basement membrane and the loss of glomerular endothelial cells and capillaries, together with inflammatory cell infiltration, fibrin exudation, rupture of the glomerular basement membrane, and/or crescent formation. In addition, the injured capillaries in the chronic glomerular lesions were characterized by the loss of CD34+ glomerular endothelial cells and capillaries exhibiting segmental and global glomerular sclerosis with or without fibrous crescents. In the acute glomerular lesions, the presence of endocapillary hypercellularity, fibrinoid necrosis, and cellular and fibrocellular crescents correlated significantly with hematuria, with or without proteinuria. In the chronic glomerular lesions, a significant relationship was evident between segmental or global sclerosis and proteinuria and/or the serum creatinine level. In conclusion, injuries of glomerular capillaries and the loss of endothelial cells occurred in the acute and chronic glomerular lesions in IgAN and may contribute to the development of hematuria, proteinuria, and renal dysfunction. PMID- 26826421 TI - SMYD2 overexpression is associated with tumor cell proliferation and a worse outcome in human papillomavirus-unrelated nonmultiple head and neck carcinomas. AB - Human papillomavirus (HPV)-unrelated head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease, and there are no suitable prognostic or predictive markers. The SET and MYND domain-containing protein 2 (SMYD2), a lysine methyltransferase for histone H3K36 and p53K370, that regulates transcription was previously found to be a cancer-promoting gene in esophageal squamous cell carcinoma. In this study, we investigated whether SMYD2 is a possible oncogene and a prognostic indicator in HPV-unrelated, multiple and nonmultiple HNSCC. Among 197 HPV-unrelated HNSCC cases, overexpression of SMYD2 protein was detected in 75 (60%) of 126 nonmultiple cases and 51 (70%) of 71 multiple cases. In nonmultiple cases, patients with SMYD2-overexpressing tumors had a worse overall survival rate than did those with nonexpressing tumors (P = .017, log-rank test), and SMYD2 positivity was independently associated with overall survival in the multivariate analysis (P = .003). In both nonmultiple and multiple groups, the combination of SMYD2 and p53 immunopositivity was a significant prognostic indicator (P = .027 and .015). In 5 HNSCC cell lines, overexpression of SMYD2 messenger RNA and protein was observed, but there was no notable amplification at 1q32-41.1. The proliferation of UM-SCC-17B HPV-unrelated HNSCC cell line was inhibited by knockdown of SMYD2 gene expression. These findings suggest that SMYD2 plays a role in tumor progression and might be a useful prognosticator in HPV-unrelated, nonmultiple HNSCC. PMID- 26826422 TI - Integrating biophysics with HTS-driven drug discovery projects. AB - Over the past decade biophysics has become an established discipline in HTS hit triaging, owing to its high fidelity in detecting protein-ligand interactions. Many pharma companies are using biophysical techniques to filter HTS output for false positives, as will be discussed in this review. Moreover, I will demonstrate how the earlier application of biophysics, already at the HTS assay development stage, is potentially even more impactful. Two key areas here are early mode-of-action studies and ensuring that the HTS assay and subsequent cascade are fit for purpose. Top-level results from 20 in-house projects are shown to underpin the impact of these studies. PMID- 26826423 TI - A single CRD C-type lectin from Eriocheir sinensis (EsLecB) with microbial binding, antibacterial prophenoloxidase activation and hem-encapsulation activities. AB - C-type lectins (CTLs) exist widely in crustaceans. To date, thirteen CTLs have been reported in crustaceans, and play significant roles in pathogen recognition, encapsulation of hemocytes and antimicrobial activity in the innate immune response. Based on the initial expressed sequence tags (EST) of a hepatopancreatic cDNA library, a novel CTL, designated as EsLecB, with a 470 bp open reading frame encodes a polypeptide of 156 amino acids, including a signal peptide of 19 amino acid residues and one carbohydrate-recognition domain of 131 aa residues, was cloned from the crustacean Eriocheir sinensis. By qRT-PCR analysis, EsLecB was detected in all tested tissues, and showed highest expression in hemocytes, hepatopancreas and heart. The expression of EsLecB was up-regulated following injections of PAMPs or bacteria. The recombinant protein (rEsLecB) expressed in Escherichia coli had a calcium-independent but carbohydrate-dependent microbial-binding and microbial-agglutinating, microorganism growth inhibitory and hem-encapsulation activities. Moreover, the rEsLecB could stimulate the activation of prophenoloxidase in vitro. These results indicated that EsLecB, as an antibacterial pattern recognition receptor is involved in innate immunity, and may act as an upstream detector of the prophenoloxidase activating system, which can detect pathogen invasion in E. sinensis. PMID- 26826424 TI - Macrophage migration inhibitory factor (MIF) family in arthropods: Cloning and expression analysis of two MIF and one D-dopachrome tautomerase (DDT) homologues in mud crabs, Scylla paramamosain. AB - The macrophage migration inhibitory factor (MIF) family, consisting of MIF and D dopachrome tautomerase (DDT) in vertebrates, is evolutionarily ancient and has been found across Kingdoms including vertebrates, invertebrates, plants and bacteria. The mammalian MIF family are chemokines at the top of the inflammatory cascade in combating infections. They also possess enzymatic activities, e.g. DDT catalysis results in the production of 5,6-dihydroxyindole (DHI), a precursor of eumelanin. MIF-like genes are widely distributed, but DDT-like genes have only been described in vertebrates and a nematode. In this report, we cloned a DDT like gene, for the first time in arthropods, and a second MIF in mud crab. The mud crab MIF family have a three exon/two intron structure as seen in vertebrates. The identification of a DDT-like gene in mud crab and other arthropods suggests that the separation of MIF and DDT preceded the divergence of protostomes and deuterostomes. The MIF family is differentially expressed in tissues of adults and during embryonic development and early life. The high level expression of the MIF family in immune tissues, such as intestine and hepatopancreas, suggests an important role in mud crab innate immunity. Mud crab DDT is highly expressed in early embryos, in megalops and crablets and this coincides with the requirement for melanisation in egg chorion tanning and cuticular hardening in arthropods, suggesting a potential novel role of DDT in melanogenesis via its tautomerase activity to produce DHI in mud crab. The clarification of the presence of both MIF and DDT in this report paves the way for further investigation of their functional roles in immunity and in melanogenesis in mud crab and other arthropods. PMID- 26826425 TI - Two novel LRR-only proteins in Chlamys farreri: Similar in structure, yet different in expression profile and pattern recognition. AB - Leucine-rich repeat (LRR)-only proteins could mediate protein-ligand and protein protein interactions and be involved in the immune response. In the present study, two novel LRR-only proteins, CfLRRop-2 and CfLRRop-3, were identified and characterized from scallop Chlamys farreri. They both contained nine LRR motifs with the consensus signature sequence LxxLxLxxNxL and formed typical horseshoe structure. The CfLRRop-2 and CfLRRop-3 mRNA transcripts were constitutively expressed in haemocytes, muscle, mantle, gill, haepatopancreas and gonad, with the highest expression level in haepatopancreas and gill, respectively. During the ontogenesis of scallop, the mRNA transcripts of CfLRRop-2 were kept at a high level in oocytes and embryos, while those of CfLRRop-3 were expressed at a rather low level from oocytes to blastula. Their mRNA transcripts were significantly increased after the stimulation of lipopolysaccharide (LPS), peptidoglycan (PGN), glucan (GLU) and polyinosinic-polycytidylic acid (poly I:C), and the mRNA expression of CfLRRop-2 rose more intensely than that of CfLRRop-3. After the suppression of CfTLR (previously identified Toll-like receptor in C. farreri) via RNA interference (RNAi), CfLRRop-3 mRNA transcripts increased more intensely and lastingly than those of CfLRRop-2. The rCfLRRop-3 protein could bind LPS, PGN, GLU and poly I:C, while rCfLRRop-2 exhibited no significant binding activity to them. Additionally, rCfLRRop-2 could significantly induce the release of TNF alpha from the mixed primary cultured scallop haemocytes, but rCfLRRop-3 failed. These results collectively indicated that CfLRRop-2 might act as an immune effector or pro-inflammatory factor, while CfLRRop-3 would function as a pattern recognition receptor (PRR), suggesting the function of LRR-only protein family has differentiated in scallop. PMID- 26826426 TI - Grass carp TGF-beta1 impairs IL-1beta signaling in the inflammatory responses: Evidence for the potential of TGF-beta1 to antagonize inflammation in fish. AB - In the present study, effects of TGF-beta1 on IL-1beta signaling during inflammatory response were examined in grass carp. In grass carp head kidney leukocytes (HKLs), LPS significantly induced the mRNA expression of grass carp TGF-beta1 (gcTGF-beta1) and IL-1beta, indicating the involvement of TGF-beta1 and IL-1beta in inflammatory process. Using anti-IL-1beta antibody to neutralize the endogenous IL-1beta, we found that stimulation of IL-1beta mRNA expression by LPS was independent on IL-1beta itself. Interestingly, recombinant gcTGF-beta1 (rgcTGF-beta1) suppressed basal and LPS-stimulated IL-1beta mRNA expression in spite of immunoneutralizing endogenous IL-1beta or not. Given that IL-1beta receptor signaling molecule and natural IL-1beta inhibitors are the important regulators in IL-1beta signaling and activity, the effect of LPS on these molecules' expression was determined in HKLs. Results showed that LPS significantly enhanced the mRNA levels of IL-1 receptor type I (IL-1RI) and II (IL-1RII), IL-1R accessory protein (IL-1Racp) and novel IL-1 family member (nIL 1F). Moreover, the induction of IL-1RII, IL-1Racp and nIL-1F by LPS was IL-1beta dependent since IL-1beta immunoneutralization abolished these inductions, implying the involvement of IL-1beta auto-induction in these effects. Consistently, TGF-beta1 could block basal IL-1RI and nIL-1F mRNA expression, and LPS-induced IL-1RI, IL-1Racp and nIL-1F mRNA expression, suggesting these molecules as the regulatory sites for TGF-beta1 to modulate IL-1beta signaling. Subsequent in vivo studies showed that bacterial challenge significantly up regulated IL-1beta mRNA expression with a rapid and transient pattern and TGF beta1 mRNA expression with a relatively time-delayed kinetics in head kidney. These expression patterns coincide with their pro-inflammatory and anti inflammatory roles, respectively. As expected, rgcTGF-beta1 could suppress bacterial-induced IL-1beta mRNA expression, strengthening the anti-inflammatory role of TGF-beta1 in vivo. Taken together, these results to our knowledge provide the first evidence for inducible TGF-beta1 expression in inflammatory process, as well as the induction of inflammatory stimuli on IL-1beta expression and signaling. In turn, TGF-beta1 suppressed the proinflammatory process in vitro and in vivo presumably via interfering IL-1beta expression and signaling in inflammatory response, highlighting the potential of TGF-beta1 in the control of inflammation in fish. PMID- 26826427 TI - Relationship between vitamin D status and vascular complications in patients with type 2 diabetes mellitus. AB - We aimed to investigate the association between serum 25-hydroxyvitamin D (25[OH]D) and microvascular complications in type 2 diabetes mellitus (T2DM) patients. It was hypothesized that lower 25(OH)D would be associated with increased microvascular complications in T2DM. A total of 257 T2DM patients (111 men, 146 women) who underwent diabetic microvascular complication (peripheral neuropathy, nephropathy, retinopathy) studies were recruited. Patients were categorized into 3 groups according to vitamin D status: vitamin D sufficient (n = 41, 25[OH]D >= 20 ng/mL), vitamin D insufficient (n = 132, 10 <= 25[OH]D < 20 ng/mL), and vitamin D deficient (n = 84, 25[OH]D < 10 ng/mL). In men, the prevalence of diabetic peripheral neuropathy (DPN) was significantly higher in patients with vitamin D deficiency than in those with insufficiency or sufficiency (38%, 11.7%, and 10%, respectively; P = .005). In addition, the prevalence of diabetic nephropathy (DN) was significantly higher in women with vitamin D deficiency than in the other 2 groups (40%, 20.6%, and 0%; P = .007). Compared with men in the vitamin D-sufficient group (reference), men in the vitamin D-deficient group had an increased risk of DPN after adjusting for confounding factors (odds ratio, 7.79; 95% confidence interval, 1.52-40.05). For women, when the vitamin D-sufficient group was used as a reference, those in the vitamin D-deficient group had an increased risk of DN after adjusting for confounding factors (odds ratio, 4.27; 95% confidence interval, 1.58-11.56). This present study found that a serum 25(OH)D level less than 10 ng/mL is independently associated with increased DPN in male patients and increased DN in female patients with T2DM. PMID- 26826428 TI - Fermented food intake is associated with a reduced likelihood of atopic dermatitis in an adult population (Korean National Health and Nutrition Examination Survey 2012-2013). AB - The prevalence of atopic dermatitis (AD) has continuously increased throughout the world in every age group, and the recent increase in AD in Korean adults may be related to changes in nutrient intakes due to westernization of dietary patterns. We hypothesized that the prevalence of AD is associated with the different dietary patterns and fermented food intakes of the Korean adult population. We examined the hypothesis using 9763 adults 19 years or older using the 2012-2013 Korean National Health and Nutrition Examination Survey. We identified 4 dietary patterns in addition to that including fermented foods using principal component analysis on data obtained from a 116-item validated semiquantitative food frequency questionnaire: meat and processed foods; vegetables, fruits, legumes, seafood, and seaweed; rice and grains; and coffee, chocolate, and ice cream. Adjusted odds ratios (ORs) for AD were calculated according to dietary patterns after adjusting for potential confounders. High levels of consumption (>92 times/month) of fermented foods such as doenjang, chungkookjang, kimchi, fermented seafood, makgeolli, and beer were associated with a lower prevalence of AD (OR, 0.56; 95% confidence interval [CI], 0.37 0.84). In contrast, high levels of consumption of meat and processed foods were strongly associated with the prevalence of AD (OR, 2.42; 95% CI, 1.48-3.94). Interestingly, the consumption of coffee, chocolate, and ice cream was significantly negatively associated with the prevalence of AD (OR, 0.53; 95% CI, 0.34-0.82). In conclusion, the hypothesis was accepted. The results can be applied to nutrition education programs for the general population to decrease risk factors for AD. PMID- 26826429 TI - Conjugated linoleic acid prevents high glucose-induced hypertrophy and contractile dysfunction in adult rat cardiomyocytes. AB - Diabetes mellitus is associated with increased risk and incidence of cardiovascular morbidity and mortality, independently of other risk factors typically associated with diabetes such as coronary artery disease and hypertension. This promotes the development of a distinct condition of the heart muscle known as diabetic cardiomyopathy. We have previously shown that conjugated linoleic acid (CLA) prevents endothelin-1-induced cardiomyocyte hypertrophy. However, the effects of CLA in preventing alterations in cardiomyocyte structure and function due to high glucose are unknown. We therefore hypothesized that CLA will have protective effects in an in vitro model of diabetic cardiomyopathy using adult rat cardiomyocytes exposed to high glucose. Our results demonstrate that subjecting adult rat cardiomyocytes to high glucose (25 mmol/L) for 24 hours significantly impaired the contractile function as evidenced by decreases in maximal velocity of shortening, peak shortening, and maximal velocity of relengthening. High glucose-induced contractile dysfunction was inhibited by pretreatment with CLA (30 MUmol/L; 1 hour). In addition to contractile aberrations, exposing adult rat cardiomyocytes to high glucose for 48 hours induced cardiomyocyte hypertrophy. High glucose-induced cardiomyocyte hypertrophy was likewise prevented by CLA. The antihypertrophic effects of CLA were abolished when cardiomyocytes were pretreated with the pharmacologic inhibitor of peroxisome proliferator-activated receptor gamma, GW9662 (1 MUmol/L). In conclusion, our findings show that exposing cardiomyocytes to high glucose results in cardiomyocyte functional and structural abnormalities, and these abnormalities are prevented by pretreatment with CLA and mediated, in part, by peroxisome proliferator-activated receptor gamma activation. PMID- 26826431 TI - The effects of a 5-HT5A receptor antagonist in a ketamine-based rat model of cognitive dysfunction and the negative symptoms of schizophrenia. AB - Serotonin (5-HT) receptors still represent promising targets for the development of novel multireceptor or stand-alone antipsychotic drugs with a potential to ameliorate cognitive impairments and negative symptoms in schizophrenia. The 5 HT5A receptor, one of the least known members of the serotonin receptor family, has also drawn attention in this regard. Although the antipsychotic efficacy of 5 HT5A antagonists is still equivocal, recent experimental data suggest the cognitive-enhancing activity of this strategy. The aim of the present study was to evaluate pro-cognitive and pro-social efficacies of the 5-HT5A receptor antagonist in a rat pharmacological model of schizophrenia employing the administration of the NMDA receptor antagonist, ketamine. The ability of SB 699551 to reverse ketamine-induced cognitive deficits in the attentional set shifting task (ASST) and novel object recognition task (NORT) was examined. The compound's efficacy against ketamine-induced social withdrawal was assessed in the social interaction test (SIT) and in the social choice test (SCT). The results demonstrated the efficacy of SB-699551 in ameliorating ketamine-induced impairments on the ASST and NORT. Moreover, the tested compound also enhanced set shifting performance in cognitively unimpaired control rats and improved object recognition memory in conditions of delay-induced natural forgetting. The pro social activity of SB-699551 was demonstrated on both employed paradigms, the SIT and SCT. The present study suggests the preclinical efficacy of a strategy based on the blockade of 5-HT5A receptors against schizophrenia-like cognitive deficits and negative symptoms. The utility of this receptor as a target for improvement of cognitive and social dysfunctions warrants further studies. PMID- 26826430 TI - Inhibition of lysyl oxidase by prostaglandin E2 via EP2/EP4 receptors in human amnion fibroblasts: Implications for parturition. AB - The underlying mechanism leading to rupture of the membranes at parturition is not fully understood. Lysyl oxidase (LOX) cross-links collagen fibrils thereby increasing the tensile strength of the membranes. Thus, understanding the regulation of LOX expression may be of crucial importance for elucidation of the process of rupture of the fetal membranes. Prostaglandin E2 (PGE2), mainly produced in the amnion, plays crucial roles during human parturition. However it is not known whether PGE2 regulates LOX expression in the fetal membranes. Using primary human amnion fibroblasts, we showed that addition of PGE2 decreased LOX mRNA and protein levels, which were blocked by inhibition of EP2/EP4 receptors and the receptor-coupled cAMP/PKA pathway. EP2/EP4 receptor agonists and stimulators of the cAMP/PKA pathway consistently decreased LOX expression. Furthermore, PGE2 induced cyclo-oxygenase-2 (COX-2) expression, a key enzyme in PGE2 production, via an EP2 and EP4 receptor-coupled cAMP/PKA pathway. Small interfering RNA-mediated knock-down of COX-2 expression significantly increased the basal expression of LOX. In addition, an increase in COX-2 and a reciprocal decrease in LOX abundance occurred in amnion tissue following labor at term. In conclusion, we have revealed a feed-forward loop of induction of COX-2 and reduction in LOX expression by PGE2 acting via an EP2/EP4 receptor-coupled cAMP/PKA pathway in human amnion fibroblasts toward the end of gestation, which may play a significant role in the rupture of fetal membranes. PMID- 26826432 TI - Immunologic Autograft Engineering and Survival in Non-Hodgkin Lymphoma. AB - Retrospective studies have reported that the collected and infused autograft absolute lymphocyte count (A-ALC) affects clinical outcomes after autologous peripheral hematopoietic stem cell transplantation (APHSCT). We hypothesized that manipulation of the apheresis machine to target a higher A-ALC dose would translate into prolonged progression-free survival (PFS) in patients with non Hodgkin lymphoma (NHL) undergoing APHSCT. Between December 2007 and October 2010, we performed a double-blind, phase III, randomized study randomly assigning 122 patients with NHL to undergo collection with the Fenwal Amicus Apheresis system with our standard settings (mononuclear cells offset of 1.5 and RBC offset of 5.0) or at modified settings (mononuclear cells offset of 1.5 and RBC of 6.0). The primary endpoint was PFS. Neither PFS (hazard ratio [HR] of modified to standard, 1.13; 95% confidence interval [CI], .62 to 2.08; P = .70) nor overall survival (OS) (HR modified to standard, .85; 95% CI, .39 to 1.86; P = .68) were found to differ by collection method. Collection of A-ALC between both methods was similar. Both PFS (P = .0025; HR, 2.77; 95% CI, 1.39 to 5.52) and OS (P = .004; HR, 3.38; 95% CI, 1.27 to 9.01) were inferior in patients infused with an A ALC < .5 * 10(9) lymphocytes/kg compared with patients infused with an A-ALC >= .5 * 10(9) lymphocytes/kg, regardless of the method of collection. We did not detect significant differences in clinical outcomes or in the A-ALC collection between the modified and the standard Fenwal Amicus settings; however, despite physician discretion on primary number of collections and range of cells infused, higher A-ALC infused dose were associated with better survival after APHSCT. PMID- 26826433 TI - Cardiac involvement in polymyositis and dermatomyositis. PMID- 26826434 TI - Genetic factors and systemic sclerosis. AB - Systemic sclerosis (SSc) is a rare connective tissue disease of unknown etiology characterized by chronic inflammation and fibrosis of the skin, vascular abnormalities, and variable involvement of organs including kidneys, gastrointestinal tract, heart, and lungs. SSc shows a complex etiology in which both environmental and genetic factors seem to influence the onset and outcome of the disease. We provide an extensive overview of the genetic factors and epigenetic modifications and what their knowledge has revealed in terms of etiopathogenesis of SSc. PMID- 26826435 TI - Hypothyroidism among SLE patients: Case-control study. AB - BACKGROUND: The prevalence of hypothyroidism in SLE patients varies considerably and early reports were mainly based on small cohorts. OBJECTIVES: To investigate the association between SLE and hypothyroidism. METHODS: Patients with SLE were compared with age and sex-matched controls regarding the proportion of hypothyroidism in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. RESULTS: The study included 5018 patients with SLE and 25,090 age and sex-matched controls. The proportion of hypothyroidism in patients with SLE was increased compared with the prevalence in controls (15.58% and 5.75%, respectively, P<0.001). In a multivariate analysis, SLE was associated with hypothyroidism (odds ratio 2.644, 95% confidence interval 2.405-2.908). CONCLUSIONS: Patients with SLE have a greater proportion of hypothyroidism than matched controls. Therefore, physicians treating patients with SLE should be aware of the possibility of thyroid dysfunction. PMID- 26826437 TI - Oral delivery of macromolecular drugs: Where we are after almost 100years of attempts. AB - Since the first attempt to administer insulin orally in humans more than 90years ago, the oral delivery of macromolecular drugs (>1000g/mol) has been rather disappointing. Although several clinical pilot studies have demonstrated that the oral absorption of macromolecules is possible, the bioavailability remains generally low and variable. This article reviews the formulations and biopharmaceutical aspects of orally administered biomacromolecules on the market and in clinical development for local and systemic delivery. The most successful approaches for systemic delivery often involve a combination of enteric coating, protease inhibitors and permeation enhancers in relatively high amounts. However, some of these excipients have induced local or systemic adverse reactions in preclinical and clinical studies, and long-term studies are often missing. Therefore, strategies aimed at increasing the oral absorption of macromolecular drugs should carefully take into account the benefit-risk ratio. In the absence of specific uptake pathways, small and potent peptides that are resistant to degradation and that present a large therapeutic window certainly represent the best candidates for systemic absorption. While we acknowledge the need for systemically delivering biomacromolecules, it is our opinion that the oral delivery to local gastrointestinal targets is currently more promising because of their accessibility and the lacking requirement for intestinal permeability enhancement. PMID- 26826438 TI - Amorphous solid dispersions: Rational selection of a manufacturing process. AB - Amorphous products and particularly amorphous solid dispersions are currently one of the most exciting areas in the pharmaceutical field. This approach presents huge potential and advantageous features concerning the overall improvement of drug bioavailability. Currently, different manufacturing processes are being developed to produce amorphous solid dispersions with suitable robustness and reproducibility, ranging from solvent evaporation to melting processes. In the present paper, laboratorial and industrial scale processes were reviewed, and guidelines for a rationale selection of manufacturing processes were proposed. This would ensure an adequate development (laboratorial scale) and production according to the good manufacturing practices (GMP) (industrial scale) of amorphous solid dispersions, with further implications on the process validations and drug development pipeline. PMID- 26826436 TI - "Eat me" imaging and therapy. AB - Clearance of apoptotic debris is a vital role of the innate immune system. Drawing upon principles of apoptotic clearance, convenient delivery vehicles including intrinsic anti-inflammatory characteristics and specificity to immune cells can be engineered to aid in drug delivery. In this article, we examine the use of phosphatidylserine (PtdSer), the well-known "eat-me" signal, in nanoparticle-based therapeutics making them highly desirable "meals" for phagocytic immune cells. Use of PtdSer facilitates engulfment of nanoparticles allowing for imaging and therapy in various pathologies and may result in immunomodulation. Furthermore, we discuss the targeting of the macrophages and other cells at sites of inflammation in disease. A thorough understanding of the immunobiology of "eat-me" signals is requisite for the successful application of "eat-me"-bearing materials in biomedical applications. PMID- 26826439 TI - Perspectives on the amorphisation/milling relationship in pharmaceutical materials. AB - This paper presents an overview of recent advances in understanding the role of the amorphous state in the physical and chemical transformations of pharmaceutical materials induced by mechanical milling. The following points are addressed: (1) Is milling really able to amorphise crystals?, (2) Conditions for obtaining an amorphisation, (3) Milling of hydrates, (4) Producing amorphous state without changing the chemical nature, (5) Milling induced crystal to crystal transformations: mediation by an amorphous state, (6) Nature of the amorphous state obtained by milling, (7) Milling of amorphous compounds: accelerated aging or rejuvenation, (8) Specific recrystallisation behaviour, and (9) Toward a rationalisation and conceptual framework. PMID- 26826440 TI - Are Graduating Pediatric Residents Prepared to Engage in Obesity Prevention and Treatment? AB - BACKGROUND: Little information is available to gauge residents' perceived receipt of comprehensive training and preparedness to manage children with obesity in practice. METHODS: A national, random sample of 1000 graduating pediatric residents were surveyed in 2013 on childhood overweight/obesity and preparedness to prevent and treat obesity. A composite training measure was created by summing the number of areas (10 possible) where training on overweight/obesity was received. Multivariable logistic regression explored relationships of resident and training characteristics to residents' belief that their own counseling on prevention and treatment of overweight/obesity is very effective (vs somewhat/slightly/not effective). RESULTS: Of 625 survey respondents (63% response), most (68-92%) reported receipt of training in each of 10 assessed areas on overweight/obesity prevention, assessment, and treatment. Most residents did not desire more training in the assessed areas; however, 54% wanted more training in motivational interviewing. About one-fourth believed that their own counseling on the prevention of overweight/obesity (26%) and treatment of obesity (22%) was very effective. Residents who rated their ability to use motivational interviewing as very good/excellent were more likely to rate their counseling on both the prevention and treatment of overweight/obesity as very effective (adjusted odds ratio [aOR] 4.33, 95% confidence interval [CI] 2.63-7.13; and aOR 4.69, 95% CI 2.72-8.07, respectively). Residents who received training in all 10 assessed areas were also more likely to rate their counseling on both prevention and treatment as very effective (aOR 2.58, 95% CI 1.61-4.14; aOR 2.41, 95% CI 1.46-3.97, respectively). CONCLUSIONS: Comprehensive training on overweight/obesity and inclusion of training in motivational interviewing may help residents feel better prepared to care for children with overweight/obesity. PMID- 26826441 TI - High conservation of herpes simplex virus UL5/UL52 helicase-primase complex in the era of new antiviral therapies. AB - The emergence of herpes simplex virus (HSV) resistance to current antiviral drugs, that all target the viral DNA polymerase, constitutes a major obstacle to antiviral treatment effectiveness of HSV infections, especially in immunocompromised patients. A novel and promising class of inhibitors of the HSV UL5/UL52 helicase-primase (HP) complex has been reported to hinder viral replication with a high potency. In this study, we describe the low natural polymorphism (interstrain identity >99.1% at both nucleotide and amino acid levels) of HSV HP complex subunits pUL5 and pUL52 among 64 HSV (32 HSV-1 and 32 HSV-2) clinical isolates, and we show that the HSV resistance profile to the first-line antiviral drug acyclovir (ACV) does not impact on the natural polymorphism of HSV HP complex. Genotypic tools and polymorphism data concerning HSV HP complex provided herein will be useful to detect drug resistance mutations in a relevant time frame when HP inhibitors (HPIs), i.e., amenamevir and pritelivir, will be available in medical practice. PMID- 26826442 TI - Antibody therapeutics for Ebola virus disease. AB - With the unprecedented scale of the 2014-2016 West Africa outbreak, the clinical and scientific community scrambled to identify potential therapeutics for Ebola virus disease (EVD). Passive administration of antibodies has a long successful history for prophylaxis and therapy of a variety of infectious diseases, but the importance of antibodies in EVD has been unclear and is the subject of some debate. Recent studies in non-human primates have renewed interest in the potential of antibodies to impact EVD. Currently ongoing clinical evaluation of polyclonal and monoclonal antibody therapy in EVD patients in West Africa may finally offer a definitive answer to this debate. PMID- 26826443 TI - H-reflex excitability is inhibited in soleus, but not gastrocnemius, at the short latency response of a horizontal jump-landing task. AB - Impaired spinal-level neuromuscular control is suggested to contribute to instability and injury during dynamic landing tasks. Despite this suggestion, spinal-level neuromuscular control is yet to be examined during a horizontal jump landing task. The aim of the current study was to assess changes in H-reflexes and its reliability at the short-latency response of landings from short and long distances. Eight healthy individuals (five male, three female; age, 22+/-1.2yrs; height, 178+/-8.1cm; weight, 72+/-15.7kg) participated in the study. H-reflexes were evoked at the SLR in the soleus and medial gastrocnemius muscles, during two landing conditions: 25% and 50% of maximal broad jump distance. H-reflexes were expressed relative to the background electromyography (EMG) and maximal M-wave responses (M-max). Soleus H-reflexes were inhibited when landing from shorter distance (25%, 13.9+/-7.6%; 50%, 8.3+/-6.5%; p<0.01). No change in H-reflex excitability was observed in medial gastrocnemius. Background EMG was unaltered across landing conditions. Inhibition of soleus H-reflex excitability from 25% to 50% landing condition indicates a reduced contribution of Ia-afferent feedback to the alpha-motor neuron during landings from greater distances, which may contribute to stiffness regulation at the ankle joint. Unaltered H-reflex excitability of medial gastrocnemius is most likely attributed to its functional role during the landing task. PMID- 26826444 TI - The IPD-IMGT/HLA Database - New developments in reporting HLA variation. AB - IPD-IMGT/HLA is a constituent of the Immuno Polymorphism Database (IPD), which was developed to provide a centralised system for the study of polymorphism in genes of the immune system. The IPD project works with specialist groups of nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The primary database within the IPD project is the IPD-IMGT/HLA Database, which provides a locus-specific database for the hyper-polymorphic allele sequences of the genes in the HLA system, also known as the human Major Histocompatibility Complex. The IPD-IMGT/HLA Database was first released over 17 years ago, building on the work of the WHO Nomenclature Committee for Factors of the HLA system that was initiated in 1968. The IPD-IMGT/HLA Database enhanced this work by providing the HLA community with an online, searchable repository of highly curated HLA sequences. Many of the genes encode proteins of the immune system and are hyper polymorphic, with some genes currently having over 4000 known allelic variants. Through the work of the HLA Informatics Group and in collaboration with the European Bioinformatics Institute we are able to provide public access to this data through the website, http://www.ebi.ac.uk/ipd/imgt/hla. PMID- 26826445 TI - CD4(+)HLA-G(+) regulatory T cells: Molecular signature and pathophysiological relevance. AB - The regulation of potentially harmful immune responses by regulatory T (Treg) cells is essential for maintaining peripheral immune tolerance and homeostasis. Especially CD4(+) Treg cells have been regarded as pivotal regulators of autoreactive and inflammatory responses as well as inducers of immune tolerance by using a variety of immune suppressive mechanisms. Besides the well-known classical CD4(+)CD25(+)FoxP3(+) Treg cells, CD4(+) T cells expressing the immune tolerizing molecule human leukocyte antigen G (HLA-G) have been recently described as another potent thymus-derived Treg (tTreg) cell subset. Albeit both tTreg subsets share common molecular characteristics, the mechanisms of their immunosuppressive function differ fundamentally. Dysfunction and numerical abnormalities of classical CD4(+) tTreg cells have been implicated in the pathogenesis of several immune-mediated diseases such as multiple sclerosis (MS). Clearly, a deeper understanding of the various CD4(+) tTreg subsets and also the underlying mechanisms of impaired immune tolerance in these disorders are essential for the development of potential therapeutic strategies. This review focuses on the current knowledge on defining features and functioning of HLA G(+)CD4(+) tTreg cells as well as their emerging role in various pathologies with special emphasis on the pathogenesis of MS. Furthermore, future research possibilities together with potential therapeutic applications are discussed. PMID- 26826446 TI - Autophagy and primary cilia: dual interplay. AB - Primary cilia are microtubule-based organelles for sensing of the extracellular milieu and transducing this information into the cell through a variety of molecular signaling pathways. Functioning of the primary cilium has been recently connected to autophagy, a pathway for degradation of cellular components in lysosomes. Autophagy regulates the length of the cilia by removing proteins required for ciliogenesis, a phenomenon that is molecularly different if performed by basal autophagy or when autophagy is induced in response to various stressors. Here we review the current knowledge about the dual interaction between autophagy and ciliogenesis, and discuss the potential role that deregulated ciliary autophagy could have in pathologies with alterations in autophagy and ciliogenesis. PMID- 26826448 TI - Therapy induces widespread reorganization of motor cortex after complete spinal transection that supports motor recovery. AB - Reorganization of the somatosensory system and its relationship to functional recovery after spinal cord injury (SCI) has been well studied. However, little is known about the impact of SCI on organization of the motor system. Recent studies suggest that step-training paradigms in combination with spinal stimulation, either electrically or through pharmacology, are more effective than step training alone at inducing recovery and that reorganization of descending corticospinal circuits is necessary. However, simpler, passive exercise combined with pharmacotherapy has also shown functional improvement after SCI and reorganization of, at least, the sensory cortex. In this study we assessed the effect of passive exercise and serotonergic (5-HT) pharmacological therapies on behavioral recovery and organization of the motor cortex. We compared the effects of passive hindlimb bike exercise to bike exercise combined with daily injections of 5-HT agonists in a rat model of complete mid-thoracic transection. 5-HT pharmacotherapy combined with bike exercise allowed the animals to achieve unassisted weight support in the open field. This combination of therapies also produced extensive expansion of the axial trunk motor cortex into the deafferented hindlimb motor cortex and, surprisingly, reorganization within the caudal and even the rostral forelimb motor cortex areas. The extent of the axial trunk expansion was correlated to improvement in behavioral recovery of hindlimbs during open field locomotion, including weight support. From a translational perspective, these data suggest a rationale for developing and optimizing cost effective, non-invasive, pharmacological and passive exercise regimes to promote plasticity that supports restoration of movement after spinal cord injury. PMID- 26826449 TI - Use of human stem cells in Huntington disease modeling and translational research. AB - Huntington disease (HD) is a devastating neurological disorder caused by an extended CAG repeat in exon 1 of the gene that encodes the huntingtin (HTT) protein. HD pathology involves a loss of striatal medium spiny neurons (MSNs) and progressive neurodegeneration affects the striatum and other brain regions. Because HTT is involved in multiple cellular processes, the molecular mechanisms of HD pathogenesis should be investigated on multiple levels. On the cellular level, in vitro stem cell models, such as induced pluripotent stem cells (iPSCs) derived from HD patients and HD embryonic stem cells (ESCs), have yielded progress. Approaches to differentiate functional MSNs from ESCs, iPSCs, and neural stem/progenitor cells (NSCs/NPCs) have been established, enabling MSN differentiation to be studied and disease phenotypes to be recapitulated. Isolation of target stem cells and precursor cells may also provide a resource for grafting. In animal models, transplantation of striatal precursors differentiated in vitro to the striatum has been reported to improve disease phenotype. Initial clinical trials examining intrastriatal transplantation of fetal neural tissue suggest a more favorable clinical course in a subset of HD patients, though shortcomings persist. Here, we review recent advances in the development of cellular HD models and approaches aimed at cell regeneration with human stem cells. We also describe how genome editing tools could be used to correct the HTT mutation in patient-specific stem cells. Finally, we discuss the potential and the remaining challenges of stem cell-based approaches in HD research and therapy development. PMID- 26826450 TI - Prediction of spurious HLA class II typing results using probabilistic classification. AB - While modern high-throughput sequence-based HLA genotyping methods generally provide highly accurate typing results, artefacts may nonetheless arise for numerous reasons, such as sample contamination, sequencing errors, read misalignments, or PCR amplification biases. To help detecting spurious typing results, we tested the performance of two probabilistic classifiers (binary logistic regression and random forest models) based on population-specific genotype frequencies. We trained the model using high-resolution typing results for HLA-DRB1, DQB1, and DPB1 from large samples of German, Polish and UK-based donors. The high predictive capacity of the best models replicated both in 10 fold cross-validation for each gene and in using independent evaluation data (AUC 0.820-0.893). While genotype frequencies alone provide enough predictive power to render the model generally useful for highlighting potentially spurious typing results, the inclusion of workflow-specific predictors substantially increases prediction specificity. Low initial DNA concentrations in combination with low volume PCR reactions form a major source of stochastic error specific to the Fluidigm chip-based workflow at DKMS Life Science Lab. The addition of DNA concentrations as a predictor variable thus substantially increased AUC (0.947 0.959) over purely frequency-based models. PMID- 26826451 TI - MICA/B genotyping of Tujias from Zhangjiajie, Hunan Province, China. AB - One hundred eighty-seven Tujia individuals from Zhangjiajie, Hunan Province, China were genotyped at the MICA and MICB loci using polymerase chain reaction sequence specific priming and sequencing-based typing methods. MICA and MCB genotypes are consistent with expected HW proportions. These genotype data are available in the Allele Frequencies Net Database. PMID- 26826447 TI - In vitro models of axon regeneration. AB - A variety of in vitro models have been developed to understand the mechanisms underlying the regenerative failure of central nervous system (CNS) axons, and to guide pre-clinical development of regeneration-promoting therapeutics. These range from single-cell based assays that typically focus on molecular mechanisms to organotypic assays that aim to recapitulate in vivo behavior. By utilizing a combination of models, researchers can balance the speed, convenience, and mechanistic resolution of simpler models with the biological relevance of more complex models. This review will discuss a number of models that have been used to build our understanding of the molecular mechanisms of CNS axon regeneration. PMID- 26826452 TI - Lower skeletal muscle capillarization in hypertensive elderly men. AB - Aging strongly affects the skeletal muscle and is associated with microvascular dysfunctions. Age is also a primary risk factor for the metabolic syndrome, which is a cluster of metabolic and cardiovascular symptoms. Among the metabolic syndrome components, hypertension is the most prevalent in elderly subjects and has a central role in vascular alterations. Despite critical clinical outcomes, the effects of hypertension and metabolic syndrome on skeletal muscle capillarization have poorly been investigated during aging. In the present study, muscle biopsies from normotensive young (YO) and elderly (ELc) men, and elderly men with hypertension (EL-HT) or metabolic syndrome (EL-MS) were assessed for the number of capillaries around a fiber (CAF), capillary-to-fiber perimeter exchange (CFPE), length of contact to perimeter of fiber ratio (LC/PF), capillary tortuosity, and for extracellular matrix (ECM) embedding capillaries. As capillarization and muscle mitochondrial oxidative capacity may be associated, we also investigated cytochrome c oxidase (COX) content. Our findings indicate that capillarization and COX did not change between normotensive adult and old individuals. They further reveal that hypertension in elderly men is associated with reduced CAF (ELc: 5.2 +/- 0.4, EL-HT: 4.1 +/- 0.2, P<0.02 for type I fibers; ELc: 4.1 +/- 0.2, EL-HT: 3.1 +/- 0.3, P<0.03 for type IIA fibers), CFPE (ELc: 7.9 +/- 0.7, EL-HT: 6.4 +/- 0.4 capillaries/1000 MUm, P<0.03 for type I fibers; ELc: 6.5 +/- 0.4, EL-HT: 5.2 +/- 0.4 capillaries/1000 MUm, P<0.03 for type IIA fibers), LC/PF (ELc: 23.3 +/- 1.2, EL-HT: 17.8 +/- 0.6%, P<0.01 for type I fibers; ELc: 19.8 +/- 1.1, EL-HT: 15.6 +/- 0.8%, P<0.01 for type IIA fibers) and capillary tortuosity, and with ECM endomysium fibrosis. Capillary rarefaction also correlated with lower COX content in the old hypertensive muscle. No further modification occurred with metabolic syndrome in elderly men. Collectively, our results suggest that hypertension plays a central role in muscle capillarization during aging, and that the other components of metabolic syndrome do not make major additional changes in the aged skeletal muscle capillary network. PMID- 26826453 TI - Toward better public health reporting using existing off the shelf approaches: A comparison of alternative cancer detection approaches using plaintext medical data and non-dictionary based feature selection. AB - OBJECTIVES: Increased adoption of electronic health records has resulted in increased availability of free text clinical data for secondary use. A variety of approaches to obtain actionable information from unstructured free text data exist. These approaches are resource intensive, inherently complex and rely on structured clinical data and dictionary-based approaches. We sought to evaluate the potential to obtain actionable information from free text pathology reports using routinely available tools and approaches that do not depend on dictionary based approaches. MATERIALS AND METHODS: We obtained pathology reports from a large health information exchange and evaluated the capacity to detect cancer cases from these reports using 3 non-dictionary feature selection approaches, 4 feature subset sizes, and 5 clinical decision models: simple logistic regression, naive bayes, k-nearest neighbor, random forest, and J48 decision tree. The performance of each decision model was evaluated using sensitivity, specificity, accuracy, positive predictive value, and area under the receiver operating characteristics (ROC) curve. RESULTS: Decision models parameterized using automated, informed, and manual feature selection approaches yielded similar results. Furthermore, non-dictionary classification approaches identified cancer cases present in free text reports with evaluation measures approaching and exceeding 80-90% for most metrics. CONCLUSION: Our methods are feasible and practical approaches for extracting substantial information value from free text medical data, and the results suggest that these methods can perform on par, if not better, than existing dictionary-based approaches. Given that public health agencies are often under-resourced and lack the technical capacity for more complex methodologies, these results represent potentially significant value to the public health field. PMID- 26826454 TI - Effects of sensory cueing in virtual motor rehabilitation. A review. AB - OBJECTIVES: To critically identify studies that evaluate the effects of cueing in virtual motor rehabilitation in patients having different neurological disorders and to make recommendations for future studies. METHODS: Data from MEDLINE(r), IEEExplore, Science Direct, Cochrane library and Web of Science was searched until February 2015. We included studies that investigate the effects of cueing in virtual motor rehabilitation related to interventions for upper or lower extremities using auditory, visual, and tactile cues on motor performance in non immersive, semi-immersive, or fully immersive virtual environments. These studies compared virtual cueing with an alternative or no intervention. RESULTS: Ten studies with a total number of 153 patients were included in the review. All of them refer to the impact of cueing in virtual motor rehabilitation, regardless of the pathological condition. After selecting the articles, the following variables were extracted: year of publication, sample size, study design, type of cueing, intervention procedures, outcome measures, and main findings. The outcome evaluation was done at baseline and end of the treatment in most of the studies. All of studies except one showed improvements in some or all outcomes after intervention, or, in some cases, in favor of the virtual rehabilitation group compared to the control group. CONCLUSIONS: Virtual cueing seems to be a promising approach to improve motor learning, providing a channel for non pharmacological therapeutic intervention in different neurological disorders. However, further studies using larger and more homogeneous groups of patients are required to confirm these findings. PMID- 26826455 TI - Optimized evaporation technique for leachate treatment: Small scale implementation. AB - This paper introduces an optimized evaporation technique for leachate treatment. For this purpose and in order to study the feasibility and measure the effectiveness of the forced evaporation, three cuboidal steel tubs were designed and implemented. The first control-tub was installed at the ground level to monitor natural evaporation. Similarly, the second and the third tub, models under investigation, were installed respectively at the ground level (equipped tub 1) and out of the ground level (equipped-tub 2), and provided with special equipment to accelerate the evaporation process. The obtained results showed that the evaporation rate at the equipped-tubs was much accelerated with respect to the control-tub. It was accelerated five times in the winter period, where the evaporation rate was increased from a value of 0.37 mm/day to reach a value of 1.50 mm/day. In the summer period, the evaporation rate was accelerated more than three times and it increased from a value of 3.06 mm/day to reach a value of 10.25 mm/day. Overall, the optimized evaporation technique can be applied effectively either under electric or solar energy supply, and will accelerate the evaporation rate from three to five times whatever the season temperature. PMID- 26826456 TI - An investigation of Cr(VI) removal with metallic iron in the co-presence of sand and/or MnO2. AB - This study focused on the influence of sand and/or MnO2 co-presence on the mechanism and kinetics of Cr(VI) removal with Fe(0). The process was investigated under acidic and well-mixed conditions, over the temperature range of 6-32 degrees C. It was shown that both mechanism and kinetics of the removal process were highly dependent on composition and dose of reactive mixture added to Cr(VI) solution. At 22 degrees C, indirect chemical reduction with Fe(II) was the main removal path in H2O-Fe(0)-Cr(VI) and H2O-Fe(0)-Sand-Cr(VI) system, while in H2O Fe(0)-MnO2-Cr(VI) and H2O-Fe(0)-MnO2-Sand-Cr(VI) system removal of Cr(VI) occurred mainly via adsorption on MnO2. The pseudo zero-order kinetic model provided the best match for H2O-Fe(0)-Cr(VI) and H2O-Fe(0)-Sand-Cr(VI) system, while in H2O-Fe(0)-MnO2-Cr(VI) and H2O-Fe(0)-MnO2-Sand-Cr(VI) system the process fitted well to the pseudo second-order model. Temperature influenced the efficiency and kinetics of the process in all investigated systems, and the removal mechanism only in H2O-Fe(0)-MnO2-Cr(VI) and H2O-Fe(0)-MnO2-Sand-Cr(VI) system. PMID- 26826457 TI - Water usage for natural gas production through hydraulic fracturing in the United States from 2008 to 2014. AB - Hydraulic fracturing has promoted the exploitation of shale oil and natural gas in the United States (U.S.). However, the large amounts of water used in hydraulic fracturing may constrain oil and natural gas production in the shale plays. This study surveyed the amounts of freshwater and recycled produced water used to fracture wells from 2008 to 2014 in Arkansas, California, Colorado, Kansas, Louisiana, Montana, North Dakota, New Mexico, Ohio, Oklahoma, Pennsylvania, Texas, West Virginia, and Wyoming. Results showed that the annual average water volumes used per well in most of these states ranged between 1000 m(3) and 30,000 m(3). The highest total amount of water was consumed in Texas with 457.42 Mm(3) of water used to fracture 40,521 wells, followed by Pennsylvania with 108.67 Mm(3) of water used to treat 5127 wells. Water usages ranged from 96.85 Mm(3) to 166.10 Mm(3) annually in Texas from 2012 to 2014 with more than 10,000 wells fractured during that time. The percentage of water used for hydraulic fracturing in each state was relatively low compared to water usages for other industries. From 2009 to 2014, 6.55% (median) of the water volume used in hydraulic fracturing contained recycled produced water or recycled hydraulic fracturing wastewater. 10.84% (median) of wells produced by hydraulic fracturing were treated with recycled produced water. The percentage of wells where recycled wastewater was used was lower, except in Ohio and Arkansas, where more than half of the wells were fractured using recycled produced water. The median recycled wastewater volume in produced wells was 7127 m(3) per well, more than half the median value in annual water used per well 11,259 m(3). This indicates that, for wells recycling wastewater, more than half of their water use consisted of recycled wastewater. PMID- 26826458 TI - Curcumin shows excellent therapeutic effect on psoriasis in mouse model. AB - Curcumin is an active herbal ingredient possessing surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. Recently, it has been reported to exhibit inhibitory activity on potassium channel subtype Kv1.3. As Kv1.3 channels are mainly expressed in T cells and play a key role in psoriasis, the effects of curcumin were investigated on inflammatory factors secretion in T cells and psoriasis developed in keratin (K) 14-vascular endothelial growth factor (VEGF) transgenic mouse model. Results showed that, 10 MUM of curcumin significantly inhibited secretion of inflammatory factors including interleukin (IL)-17,IL-22, IFN-gamma, IL-2, IL-8 and TNF-alpha in T cells by 30-60% in vitro. Notably, more than 50% of T cells proliferation was inhibited by application of 100 MUM curcumin. Compared with severe psoriatic symptoms observed in the negative control mice, all psoriasis indexes including ear redness, weight, thickness and lymph node weight were significantly improved by oral application of curcumin in treatment mouse group. Histological examination indicated that curcumin had anti inflammatory function in the experimental animals. More than 50% level of inflammatory factors including TNF-alpha, IFN-gamma, IL-2, IL-12, IL-22 and IL-23 in mouse serum was decreased by curcumin treatment as well as cyclosporine. Compared with renal fibrosis observed in the mouse group treated by cyclosporine, no obvious side effect in mouse kidney was found after treated by curcumin. Taken together, curcumin, with high efficacy and safety, has a great potential to treat psoriasis. PMID- 26826459 TI - Abdominal massage for the alleviation of symptoms of constipation in people with Parkinson's: a randomised controlled pilot study. AB - BACKGROUND: constipation is one of the most common non-motor features of Parkinson's affecting up to 90% of patients. In severe cases, it can lead to hospitalisation and is usually managed with laxatives which in themselves can lead to side effects. Abdominal massage has been used as adjunct in the management of constipation in various populations, but not in those with Parkinson's. OBJECTIVE: the primary objective was to test the recruitment, retention and the appropriateness of the intervention methods and outcome measures. METHODS: thirty-two patients with Parkinson's were recruited from three movement disorder clinics and were randomised to receive either 6 weeks of daily abdominal massage plus lifestyle advice on managing constipation (Intervention Group, n = 16) or lifestyle advice (Control Group, n = 16). Data were collected prior to group allocation (Baseline), at Week 6 (following intervention) and 4 weeks later (Week 10). Outcome tools included the Gastrointestinal Rating Scale and a bowel diary. RESULTS: constipation has a negative impact on quality of life. The study recruited to target, retention was high and adherence to the study processes was good. The massage was undertaken as recommended during the 6 weeks of intervention with 50% continuing with the massage at 10 weeks. Participants in both groups demonstrated an improvement in symptoms, although this was not significantly different between the groups. CONCLUSION: abdominal massage, as an adjunct to management of constipation, offers an acceptable and potentially beneficial intervention to patients with Parkinson's. PMID- 26826460 TI - Decreased DNA repair gene XRCC1 expression is associated with radiotherapy induced acute side effects in breast cancer patients. AB - DNA repair plays a critical role in response to ionizing radiation (IR) and developing of radiotherapy induced normal tissue reactions. In our study, we investigated the association of radiotherapy related acute side effects, with X ray repair cross complementing group 1 (XRCC1) and Poly (ADP-ribose) polymerase 1 (PARP1) DNA repair gene expression levels, their changes in protein expression and DNA damage levels in breast cancer patients. The study included 40 women with newly diagnosed breast cancer; an experimental case group (n=20) with acute side effects and the control group (n=20) without side effects. For gene and protein expression analysis, lymphocytes were cultured for 72 h and followed by in vitro 2 Gray (Gy) gamma-irradiation. For detection of DNA damage levels, lymphocytes were irradiated with in vitro 2 Gy gamma-rays and followed by incubation for 72 h. XRCC1 mRNA and protein expression levels were significantly higher in controls than in experimental cases (P=0.020). In terms of DNA damage levels, an increased frequency of micronucleus (MN) was observed in experimental cases versus controls, but this association was not significant (P=0.206). We also observed a significant negative correlation between MN frequency and XRCC1 protein levels in experimental (r=-0.469, P=0.037) vs control (r=-0.734, P<0.001). Our results suggested that decreased XRCC1 expression levels might be associated with the increased risk of therapeutic IR-related acute side effects in patients with breast cancer. PMID- 26826461 TI - Role of microRNA 21 in diabetes and associated/related diseases. AB - Diabetes mellitus (DM) is a disease related to metabolic disorder and becoming an epidemic in developing countries. Current treatments for DM include modified lifestyle practice, obesity treatment, oral hypoglycemic agents, and insulin sensitizers, yet no cure is available in sight for the disease, despite it requires new insight into the molecular and pathophysiology. MicroRNAs (miRNAs) are small noncoding RNAs considered as of greater biological importance and controls molecular signaling pathways in diabetic pathogenesis. The microRNA 21 is an important microRNA frequently upregulated in all types of diseases suggesting that it plays an important role in cell proliferation, and apoptosis. The present mini review highlights the recent investigations related to the importance of miR-21 in different types of DM based on the up-to-date reports. PMID- 26826462 TI - Genetic analysis and functional characterization of novel mutations in a series of patients with atypical hemolytic uremic syndrome. AB - Atypical hemolytic uremic syndrome (aHUS) is a rare disorder caused by dysregulation of the complement alternative pathway, and associated with mutations in genes of complement components and regulators. In the recent years several studies have been published describing these mutations, however, no data is available from the Central and Eastern European region. In this study we present a detailed genetic analysis of our 30 patients, hospitalized with the diagnosis of aHUS in the past 7 years. We analyzed the genetic variants of genes CFH, CFI, CD46, THBD, CFB and C3; furthermore the possible effect of mutations that may alter the function or level of factor H protein was also investigated. We identified 27 (12 novel and 15 previously described) potentially disease causing mutations in the candidate genes in 23 patients. Genetic analysis of family members revealed that in most cases the disease develops in individuals with multiple genetic risk factors, which may explain the low penetrance of the mutations. Here we showed that two novel mutations (p.W198R, p.P1161T) and a previously reported one (p.R1215Q) in CFH caused impaired regulation as indicated by increased lysis in hemolytic test, while four CFH mutations (p.V609D, p.S722X, p.T1216del and p.C448Y) were associated with decreased factor H protein level in serum as determined by allele-specific immunoassay. These results further point to the necessity of complete genetic workup of patients with aHUS and to the importance of functional characterization of novel variations. PMID- 26826463 TI - Immunogenicity and protective efficacy of Brucella abortus recombinant protein cocktail (rOmp19+rP39) against B. abortus 544 and B. melitensis 16M infection in murine model. AB - In this study, the immunogenicity and protective efficacy of recombinant proteins Omp19 (rO) and P39 (rP) from Brucella abortus were evaluated individually and compared with the cocktail protein (rO+rP) against B. abortus 544 and Brucella melitensis 16M infection in BALB/c mouse model. Intra-peritoneal (I.P.) immunization with rO+rP cocktail developed substantially higher antibody titers predominant with Th1 mediated isotypes (IgG2a/2b). Western blot analysis using anti-rO+rP antibodies showed specific reactivity with native Omp19 (19 kDa) and P39 (39 kDa) among whole cell proteins of B. abortus and B. melitensis. Splenocytes extracted from rO+rP immunized mice induced significantly (P<0.001) higher proliferative responses at 30 MUg/ml with considerable expression of pro inflammatory cytokines (IFN-gamma, IL-2 and IL-12) than rO and rP. Macrophage cell (RAW 264.7) monolayer supplemented with anti-rO+rP polysera exhibited enhanced viability against challenge with B. abortus 544 (72.27%) and B. melitensis 16M (68.57%). On the other hand, individual anti-rO and anti-rP polysera resulted in relatively lesser protection against the pathogens (64.79%, 54.45% and 47.13%, 45.11%, respectively). Immunized group of mice when I.P. challenged with 5 * 10(4) CFU of B. abortus 544 and B. melitensis 16M were found significantly (P<0.001) protected in the rO+rP group (log units of protection, spleen: 2.38, 2.12; liver: 1.04, 0.81, respectively) than in rO (spleen: 1.43, 1.21; liver: 0.7, 0.47) and rP (spleen: 1.24, 1.17; liver: 0.65, 0.34). Findings from this study depicted that rO+rP cocktail is highly immunogenic with the Th1 predominant serum antibody titers and T-cell mediated immune protection, would be a valuable intervention in the development of a safer and improved Brucella vaccine. PMID- 26826464 TI - Knowledge acquisition and research evidence in autism: Researcher and practitioner perspectives and engagement. AB - BACKGROUND: Government policy and national practice guidelines have created an increasing need for autism services to adopt an evidence-based practice approach. However, a gap continues to exist between research evidence and its application. This study investigated the difference between autism researchers and practitioners in their methods of acquiring knowledge. METHODS: In a questionnaire study, 261 practitioners and 422 researchers reported on the methods they use and perceive to be beneficial for increasing research access and knowledge. They also reported on their level of engagement with members of the other professional community. RESULTS: Researchers and practitioners reported different methods used to access information. Each group, however, had similar overall priorities regarding access to research information. While researchers endorsed the use of academic journals significantly more often than practitioners, both groups included academic journals in their top three choices. The groups differed in the levels of engagement they reported; researchers indicated they were more engaged with practitioners than vice versa. CONCLUSIONS: Comparison of researcher and practitioner preferences led to several recommendations to improve knowledge sharing and translation, including enhancing access to original research publications, facilitating informal networking opportunities and the development of proposals for the inclusion of practitioners throughout the research process. PMID- 26826465 TI - The consolidation of a motor skill in young adults with ADHD: Shorter practice can be better. AB - Practice on a given sequence of movements can lead to robust procedural memory (skill). In young adults, in addition to gains in performance accrued during practice, speed and accuracy can further improve overnight; the latter, delayed, 'offline', gains are thought to emerge when procedural memory consolidation processes are completed. A recent study suggested that female college students with ADHD show an atypical procedural memory consolidation phase, specifically, gaining speed but losing accuracy, overnight. Here, to test if this accuracy loss reflected a cost of overlong training in adults with ADHD, we compared the performance of female college students with (N=16) and without (N=16) ADHD, both groups given a shorter training protocol (80 rather than the standard 160 task repetitions). Speed and accuracy were recorded before training, immediately after, and at 24-h and 2 weeks post-training. The shortened practice session resulted in as robust within-session gains and additional overnight gains in speed at no costs in accuracy, in both groups. Moreover, individuals with ADHD showed as robust speed gains and retention as in the longer training session, but the costs in accuracy incurred in the latter were eliminated. The shortening of practice sessions may benefit motor skill acquisition in ADHD. PMID- 26826466 TI - Further evidence of poor comprehenders' difficulty with expressive writing: Exploring the role of inferences. AB - Several studies have demonstrated that children with poor reading comprehension abilities have weak expressive writing skills too. The aim of the present research was to establish whether poor comprehenders' low performance in expressive writing is mediated by the need to produce relevant inferences to construct the narrative. To do so, we compared two conditions: in one, the children's comprehension of the story relied partly on their ability to draw crucial causal inferences; in the other, all the information needed to follow the sequence of events was provided in pictures. Irrespective of the condition, poor comprehenders (aged 8-10 years) produced less effective written texts. Analyzing the use of connectives shed some light on the characteristics of the poor comprehenders' written narratives, which seemed to be less cohesive. The poor comprehenders tended to use more additive connectives than causal connectives, which is why their texts resembled a list of events with a description of each picture. PMID- 26826467 TI - Towards a structural understanding of RNA synthesis by negative strand RNA viral polymerases. AB - Negative strand RNA viruses (NSVs), which may have segmented (sNSV) or non segmented genomes (nsNSV) are responsible for numerous serious human infections such as Influenza, Measles, Rabies, Ebola, Crimean Congo Haemorrhagic Fever and Lassa Fever. Their RNA-dependent RNA polymerases transcribe and replicate the nucleoprotein coated viral genome within the context of a ribonucleoprotein particle. We review the first high resolution crystal and cryo-EM structures of representative NSV polymerases. The heterotrimeric Influenza and single-chain La Crosse orthobunyavirus polymerase structures (sNSV) show how specific recognition of both genome ends is achieved and is required for polymerase activation and how the sNSV specific 'cap-snatching' mechanism of transcription priming works. Vesicular Stomatitis Virus (nsNSV) polymerase shows a similar core architecture but has different flexibly linked C-terminal domains which perform mRNA cap synthesis. These structures pave the way for a more complete understanding of these complex, multifunctional machines which are also targets for anti-viral drug design. PMID- 26826468 TI - Two- and 3-year-olds integrate linguistic and pedagogical cues in guiding inductive generalization and exploration. AB - Young children can in principle make generic inferences (e.g., "doffels are magnetic") on the basis of their own individual experience. Recent evidence, however, shows that by 4 years of age children make strong generic inferences on the basis of a single pedagogical demonstration with an individual (e.g., an adult demonstrates for the child that a single "doffel" is magnetic). In the current experiments, we extended this to look at younger children, investigating how the mechanisms underlying this phenomenon are integrated with other aspects of inductive inference during early development. We found that both 2- and 3-year olds used pedagogical cues to guide such generic inferences, but only so long as the "doffel" was linguistically labeled. In a follow-up study, 3-year-olds, but not 2-year-olds, continued to make this generic inference even if the word "doffel" was uttered incidentally and non-referentially in a context preceding the pedagogical demonstration, thereby simply marking the opportunity to learn about a culturally important category. By 3 years of age, then, young children show a remarkable ability to flexibly combine different sources of culturally relevant information (e.g., linguistic labeling, pedagogy) to make the kinds of generic inferences so central in human cultural learning. PMID- 26826469 TI - The nature of orthographic learning in self-teaching: Testing the extent of transfer. AB - The current study was designed to test how orthographic learning, or the learning of the spelling patterns of words, happens within the self-teaching paradigm. One possibility is that orthographic learning occurs on a word-specific basis. Two other possibilities are that orthographic learning transfers specifically to the processing of novel words that are morphologically related or that it transfers to novel words that are orthographically similar, regardless of morphological relationship. In an orthographic learning paradigm, we asked children in Grades 3 and 5 to read nonwords embedded in short stories. In a between-participants design, some children read nonwords that were base forms, others read nonwords that were morphologically complex forms, and others read nonwords that were orthographically complex forms (e.g., feap, feaper, and feaple, respectively). Children completed an orthographic choice task with the same items as in the stories. To evaluate transfer of learning, children also completed orthographic choices for the two forms of the nonwords not seen in the stories. Results indicated that children's orthographic learning affected processing of novel items that appeared to be morphologically related as well as those that shared only orthographic structure (e.g., both feaper and feaple). Additional analyses showed that these effects were held across cases when children did and did not successfully decode the novel words in the learning experience, although successful decoding did lead to higher levels of orthographic learning and transfer. Together, the findings suggest that children's prior experiences affect their processing of novel words that share orthographic similarity, likely reflecting a role for orthographic analogies in the self-teaching process. PMID- 26826470 TI - Maxillary sinus floor augmentation and dental implant placement using dentin matrix protein-1 gene-modified bone marrow stromal cells mixed with deproteinized boving bone: A comparative study in beagles. AB - OBJECTIVE: The aim of the study was to evaluate the effects of the combined use of dentin matrix protein-1 (DMP1) gene-modified bone marrow stromal cells (BMSCs) and Bio-Oss((r)) for maxillary sinus floor augmentation (MSFA) implant placement in dogs. MATERIALS AND METHODS: BMSCs were derived from bone marrow of six beagles and cultured. The cells were transduced with a lentiviral vector overexpressing the DMP1 gene and enhanced green fluorescent protein (EGFP) gene (Lenti-DMP1/EGFP) in test group, and with a lentiviral vector encoding EGFP gene (Lenti-EGFP) in control group. Six dogs received sinus augmentations using the bilateral approach with a simultaneous implant placement at each site respectively. At the same concentration, 2*10(7) cells/ml, one sinus was grafted using a mixture of autologous DMP1/EGFP gene-modified BMSCs and Bio-Oss((r)) (DMP1 group), and the contralateral sinus was grafted with autologous EGFP gene modified bMSCs and Bio-Oss((r)) (EGFP group). After a 3 month healing period, bone regeneration and osseointegration were evaluated using histologic and histomorphometric methods. RESULTS: The bone-implant contact (BIC) and the bone area fraction in the DMP1 group (BIC: 34.67%+/-8.23%, bone area fraction: 35.16%+/-3.32%) were significantly greater compared with the EGFP group (BIC: 26.06%+/-5.16%, bone area fraction: 20.74%+/-1.63%) (P<0.05). No significant difference between the residual bone substitute material volume (BSMV) in the DMP1 group (35.86+/-7.35) and the EGFP group (32.16+/-9.16) was found in our study (P>0.05). CONCLUSION: BMSCs modified with the DMP1 gene can be used as an adjunct to Bio-Oss((r)) to enhance new bone formation and the osseointegration of dental implants in MSFA of dogs. PMID- 26826471 TI - Calcium phosphate-titanium composites for articulating surfaces of load-bearing implants. AB - Calcium phosphate (CaP)-titanium (Ti) composites were processed using a commercial laser engineered net shaping (LENSTM) machine to increase wear resistance of articulating surfaces of load-bearing implants. Such composites could be used to cover the surface of titanium implants and potentially increase the lifetime of a joint replacement. It was hypothesized that adding calcium phosphate to commercially pure titanium (CP-Ti) and Ti6Al4V alloy via laser processing would decrease the material loss when subjected to wear. This added protection would be due to the in situ formation of a CaP tribofilm. Different amounts of CaP were mixed by weight with pure Ti and Ti6Al4V powders. The mixed powders were then made into cylindrical samples using a commercial LENSTM-750 system. Microstructures were observed and it was found the CaP had integrated into the titanium metal matrix. Compression test revealed that CaP significantly increased the 0.2% offset yield strength as well as the ultimate compressive strength of CP-Ti. It was found that the addition of CaP to pure titanium reduced the material loss and increased wear resistance. This was due to the formation of CaP tribofilm on the articulating surface. The in situ formed tribofilm also lowered the coefficient of friction and acted as a solid lubricant between the two interacting metal surfaces. Overall, CaP addition to Ti and its alloy Ti6Al4V show an effective way to minimize wear induced damage due to the formation of in situ tribofilm at the articulating surface, a strategy that can be utilized in various biomedical devices. PMID- 26826472 TI - The structures, cytotoxicity, apoptosis and molecular docking controlled by the aliphatic chain of palladium(II) complexes. AB - A new series of Pd(II) complexes derived from benzenealkyl dicarboxylate ligands, [Pd(Ln)(phen)] (phen=2,9-dimethyl-1,10-phenanthroline, complex 1: L1=phenylmalonate; complex 2: L2=benzylmalonate; complex 3: L3=(2 phenylethyl)malonate; complex 4: L4=(3-phenylpropyl)malonate) have been synthesized under room temperature condition. These complexes contain a long dicarboxylate aliphatic chain. They were characterized by elemental analysis, infrared spectroscopy, single crystal X-ray diffraction. The binding of complexes with fish sperm DNA (FS-DNA) was investigated by UV absorption and fluorescence spectra. Gel electrophoresis assay demonstrated the ability of the complexes to cleave the pBR322 plasmid DNA. The cytotoxic activity of the complexes was tested against two different cancer cell lines, HeLa and HL-60. Cytotoxic activity studies showed the four complexes exhibited significant cancer cell inhibitory rate. Further flow cytometry experiments showed that the cytotoxic Pd(II) complexes induced apoptosis of HL-60 tumor cell lines. The molecular dynamic simulations and docking methods were used to predict the DNA binding affinity of Pd(II) complexes by the resulting relative binding energy of complexes with DNA 6.01, -6.25, -7.24 and -7.59 kcal/mol, while with DNA-topoisomerase I (Topo I) 7.98, -9.25, -10.2 and -11.5 kcal/mol, respectively. The good visualization images supported with the experimental results of structure-activity relationship between cytotoxicity and carbon chain length. PMID- 26826473 TI - Apomaghemite as a doxorubicin carrier for anticancer drug delivery. AB - Protein cages have well-defined structures and can be chemically and biologically engineered in many ways, making them useful platforms for drug delivery applications. Taking advantage of the unique structure feature of apoferritin, a new theranostic nanocarrier is proposed herein. The apoferritin protein is effective for the encapsulation of maghemite nanoparticles and for loading a significant dose of doxorubicin (DOX) drug. This simultaneous loading of maghemite nanoparticles and DOX has been achieved using either co-encapsulation or surface-binding approaches. Maghemite nanoparticles coated with the protein apoferritin are an effective long-term MRI liver contrast agent and we report here that additionally they can serve as an anticancer drug-delivery system. In particular we show that maghemite-containing apoferritin can sustain the DOX delivery under period of 10 to 25 days depending on the environmental conditions. PMID- 26826474 TI - History of human impact on Lake Kutubu, Papua New Guinea: The geochemical signatures of oil and gas mining activities in sediments. AB - Lake Kutubu, a large tropical lake in Papua New Guinea, is well known for its ecological importance; however, there have been recent changes to the pristine nature of this lake due to activities associated with the largest oil and gas project in PNG. The aim of this study was to determine the geochemical profile of sediment cores of Lake Kutubu and to comprehend the contamination changes undergone in this lake due to mining activities utilising the hydraulic fracturing method. Sediment core profiles of Na, Mg, Al, Si, P, Ca, Ti, Cr, Fe, Mn, Ni, Cu, Zn, As, Se, Sr, Cd, Ba, Ce, Pb and U, grain size and dating analyses were conducted for five sites in the lake. Grain size and dating demonstrated that the northwest side of Lake Kutubu has sediments of allocthonous origin while the southeast sediments are of autochthonous origin. Ba was the element with the largest changes in concentrations since 1990 and the best tracer of mining activities near the lake. Sites KTB 02 and KTB 10 northwest of the lake showed the most distinct changes in element concentrations. Element enrichment factors (EF = 2.8, 4.2 and 3.2 respectively) demonstrated that Mn, Se and Ba have undergone a moderate enrichment in the lake since mining activities started. Ni, Cd and Se concentrations exceed sediment guidelines in some samples. No guideline is available for Ba, and special attention should be given to this element in this lake. This study demonstrated that Lake Kutubu oil/gas extraction activities are significant sources of elements to this lake and highlights the need for studies on the partitioning and speciation of elements to understand organism metal exposure. PMID- 26826475 TI - Liquid chromatography-tandem mass spectrometric assay for the tyrosine kinase inhibitor afatinib in mouse plasma using salting-out liquid-liquid extraction. AB - A quantitative bioanalytical liquid chromatography-tandem mass spectrometric (LC MS/MS) assay for afatinib, an irreversible inhibitor of the ErbB (erythroblastic leukemia viral oncogene homolog) tyrosine kinase family, was developed and validated. Plasma samples were pre-treated using salting-out assisted liquid liquid extraction (SALLE) with acetonitrile, magnesium chloride and a stable isotopically labeled internal standard. After dilution, the extract was directly injected into the reversed-phase liquid chromatographic system. The eluate was transferred into the electrospray interface with positive ionization and compounds were detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer. The assay was completely validated for plasma in a 0.5-500ng/ml calibration range with r(2)=0.995+/-0.002 (n=6) using linear regression with the inverse square of the concentration as the weighting factor for the calibration. Within-run precisions (n=18) were 2.7-11.7% and between-run (3 runs; n=18) precisions 3.0-14.5%. Accuracies were between 96-109% for the whole calibration range. The drug was sufficiently stable under all relevant analytical conditions. Finally, the assay was successfully applied to determine plasma drug levels and study pharmacokinetics after oral administration of afatinib to female FVB mice. PMID- 26826476 TI - Relationships between substance initiation sequence and further substance use: A French nationwide retrospective study. AB - The Gateway theory (GT) proposes that tobacco or alcohol use lead to cannabis use, which can itself be followed by other illicit drugs (OID) onset. Aim of this study was to evaluate if the order of initiation sequence could influence further substance use. Data from a 2010 population-based survey were used (22,774 subjects aged 15-64). Using reported ages at initiations, 7 sequences were identified: initiation of tobacco only (T), cannabis or OID only, tobacco followed by cannabis (T-C), cannabis followed by tobacco (C-T), alternative 2 substance sequences, gateway sequence (T-C-OID) and 3-substance alternative sequences. Logistics regressions were performed to study the impact of sequence on further use (tobacco, alcohol, cannabis and OID), and substance use disorders (SUD) (tobacco, alcohol and cannabis). The most observed sequences were T (45.5%), T-C (20.5%), C-T (5.1%) and T-C-OID (3.5%). Further use and SUD likelihoods, whatever the substance considered, increased with the number of substances previously initiated. However, for a same number of substances initiated, current use and SUD likelihoods did not significantly vary according to sequence. Polysubstance initiation appears as a better predictor of further use and SUD than the initiation sequence, questioning the GT and being more in line with a common liability to substance use. PMID- 26826477 TI - Editorial. PMID- 26826478 TI - Is it possible to limit the risks of thyroid surgery? AB - OBJECTIVE: Inferior laryngeal nerve (ILN) palsy and hypocalcemia remain the two most frequent major complications after thyroid surgery. Their occurrences may be explained by the influence of factors related to the patient, the surgical procedure, thyroid pathology, or the surgeon's technique. This study aims To assess whether systematically following a rigorous surgical technique during thyroidectomy affects postoperative complications and long-term patient recovery. METHODS: We conducted a multicenter, cross-sectional study of prospectively collected data in five high-volume referral centers enrolling all patients who underwent thyroid surgery between April 2008 and December 2009. Inferior laryngeal nerve (ILN) palsy and hypocalcemia were systematically assessed during hospitalization based on objective criteria. A six-month follow-up was conducted in cases of early complications. Multivariate regression models were computed to quantify their relationship with potential risk factors. RESULTS: A total of 3574 thyroid procedures were completed. Non-visualization of the ILN during dissection and a large thyroid mass were major risk factors for permanent ILN palsy (OR, 4.17 and 2.61, p<0.01) and persistent complications after initial injury (OR, 4.17 and 2.42, p<0.05). The presence of thyroiditis on the surgical specimen was an independent risk factor for permanent hypoparathyroidism and poor recovery after initial dysfunction (OR, 1.76 and 1.88, p<0.05). CONCLUSIONS: Thorough meticulous technique in thyroid surgery is a determinant of ILN function but fails to prevent persistent hypoparathyroidism. PMID- 26826479 TI - Indications for radioiodine administration in follicular-derived thyroid cancer. AB - Indications for radioiodine administration after thyroid cancer surgery have shifted in recent years toward personalized management, adapted to the individual risk of tumor progression. The most recent guidelines and studies favor de escalation in indications for administration, dosage and means of preparation with exogenous recombinant TSH stimulation as treatment of choice. Radioiodine administration has 3 possible objectives: * ablation of normal thyroid tissue remnants in patients with low risk of progression, using low radioiodine activity levels, with the advantage of completing disease staging on whole-body scintigraphy performed after administration of the radioiodine capsule, and of facilitating follow-up by thyroglobulin assay; * adjuvant treatment for suspected microscopic metastases in patients with intermediate or high risk of progression, using higher activity levels, with the theoretic aim of limiting recurrence and mortality; * curative treatment in high-risk patients with proven metastases, using exclusively high activity levels, with a view to improving specific survival. In future, indications for ablation and/or activity prescription may be governed by an algorithm incorporating individual baseline progression risk (essentially founded of pTNM staging) and postoperative data such as thyroglobulin level and neck ultrasound results. PMID- 26826480 TI - Follow-up of differentiated thyroid carcinoma. AB - The aim of follow-up of differentiated thyroid carcinoma (CTD) is the assessment of remission, and, in further steps, the early recognition of patients who develop a recurrence. Tools for the follow-up of CTD include the assessment of thyroglobulin and imaging procedures. Thyroglobulin (Tg) is a strong marker of persistent or recurrent disease, but it must be known that Tg antibodies may give falsely low Tg concentration. TSH stimulation, mainly by the mean of recombinant human TSH, improves the sensitivity of Tg determination. New highly sensitive assays may preclude the need for TSH stimulation, at least in some situations. In the last decades, (131)iodine whole body scan gave place to neck ultrasonography (US) as the most performing imaging procedure in the follow-up of CTD. Criteria to identify cervical lymph node suspect of metastasis have been described, and standardized procedures proposed. Finally, the proof of tumoral invasion is brought by cytological analysis of fine needle biopsies of suspicious lymph nodes. (18)FDG PET is a valuable tool for diagnosis and prognosis in metastatic patients, especially with negative (131)I WBS. Initial response to therapy, assessed by Tg determination and neck US, allows re-stratification of the risk of relapse. According to this "reassessed risk", adapted rhythms and modalities of follow-up have been recently proposed. PMID- 26826481 TI - Targeted treatments of radio-iodine refractory differentiated thyroid cancer. AB - Radio-iodine refractory metastatic thyroid cancers are rare and their management was until recently relatively complex. New therapeutic agents, kinase inhibitors, joined since the early 2000s the fight against these cancers with very promising results. These targeted agents showed for two of them (sorafenib; lenvatinib), in randomized phase III trials, a significant improvement in response rate and progressionfree survival when compared to placebo, leading to the first approval for radio-iodine refractory metastatic thyroid cancers. In parallel, patients also benefited from the development of interventional radiology techniques and organization of cares in oncology, with multidisciplinary management strengthened by the creation of a national network (TUTHYREF). PMID- 26826483 TI - Risk-benefit ratio for TSH- suppressive Levothyroxine therapy in differentiated thyroid cancer. AB - In the setting of differentiated thyroid cancer (DTC) management, < 0.1 mU/L TSH suppression has been proven to be beneficial for patients likely to have microscopic or macroscopic disease, as TSH has a direct trophic effect on thyroid cancer cells. However, the optimal degree of TSH reduction remains unclear for other categories of DTC patients with better prognosis. Excessive thyroid hormone replacement can lead to atrial fibrillation and osteoporosis. Therefore, levothyroxine dose should be carefully adjusted with respect to underlying individual health status, dynamically reassessed risk of relapse and medical monitoring. Future guidelines should give priority to a tailored approach to TSH suppression therapy in DTC patients. PMID- 26826482 TI - Local treatment of metastases from differentiated thyroid cancer. AB - OBJECTIVES: To study the various local treatments available for thyroid cancer metastases, investigate techniques and assess their advantages and limitations and roles in the overall treatment strategy for metastatic disease. RESULTS: We investigated metastases surgery, external radiation therapy, embolization, chemoembolization, cementoplasty, radiofrequency ablation and cryotherapy, describing techniques, advantages and drawbacks and possible complications. Indications were reviewed according to metastases location, and the roles of the various techniques are discussed in the overall treatment strategy for thyroid cancer metastases. Despite the advent of new targeted therapies, local treatment still has an important role to play: either palliative or, in oligometastatic involvement, curative. Even in extensive disease, it may allow postponement of tyrosine kinase inhibitor therapy, which, once initiated, has to be continued life-long, is expensive and is not free of side-effects. PMID- 26826484 TI - Molecular perspectives in differentiated thyroid cancer. AB - Progress in understanding the molecular genetics of thyroid cancer in the last 20 years has accelerated recently with the advent of high-throughput sequencing technologies known as Next-Generation Sequencing. Besides classical molecular abnormalities involving the MAPK (Mitogen Activated Protein Kinase) and PI3K (PhosphoInositide 3-Kinase) pathways that play a key role in follicular-derived thyroid tumorigenesis, new molecular abnormalities have been discovered. The major advances in recent years have been the discovery of new somatic driver gene point mutations (such as RASAL1 [RAS protein activator Like 1] mutations in follicular cancer) and/or mutations that have prognostic value (such as TERT [Telomerase reverse transcriptase] promoter mutations); new chromosomal rearrangements, usually having close connection with exposure to ionizing radiation (such as ALK [Anaplastic Lymphoma Kinase] rearrangements); and deregulation of some gene or microRNA expression representing a molecular signature. Progress made in understanding the molecular mechanisms of thyroid cancer offers new perspectives for the diagnosis of the benign or malignant status of a thyroid nodule, to refine prognosis and offer new perspectives of targeted therapy for radioiodine-refractory cancers. PMID- 26826486 TI - Transcellular route as the most probable explanation for the presence of plasminogen in mammal's milk. AB - Paracellular and transcellular route of passage of several milk metabolites, albumin, lactic acid dehydrogenase and plasminogen from the systemic circulation to milk is considered. The shortcoming of prevalence views considering paracellular leakage as the most probable explanation is highlighted. A detailed discussion explaining why transcellular route is the most probable explanation for the presence of plasminogen in milk is presented. PMID- 26826485 TI - Mapping of bionic array electric field focusing in plasmid DNA-based gene electrotransfer. AB - Molecular medicine through gene therapy is challenged to achieve targeted action. This is now possible utilizing bionic electrode arrays for focal delivery of naked (plasmid) DNA via gene electrotransfer. Here, we establish the properties of array-based electroporation affecting targeted gene delivery. An array with eight 300 MUm platinum ring electrodes configured as a cochlear implant bionic interface was used to transduce HEK293 cell monolayers with a plasmid-DNA green fluorescent protein (GFP) reporter gene construct. Electroporation parameters were pulse intensity, number, duration, separation and electrode configuration. The latter determined the shape of the electric fields, which were mapped using a voltage probe. Electrode array-based electroporation was found to require ~100 * lower applied voltages for cell transduction than conventional electroporation. This was found to be due to compression of the field lines orthogonal to the array. A circular area of GFP-positive cells was created when the electrodes were ganged together as four adjacent anodes and four cathodes, whereas alternating electrode polarity created a linear area of GFP-positive cells. The refinement of gene delivery parameters was validated in vivo in the guinea pig cochlea. These findings have significant clinical ramifications, where spatiotemporal control of gene expression can be predicted by manipulation of the electric field via current steering at a cellular level. PMID- 26826487 TI - Escape from tumor dormancy and time to angiogenic switch as mitigated by tumor induced stimulation of stroma. AB - A variety of mechanisms have been proposed to explain "cancer without disease", the state of tumor dormancy, characterized by balance in cell proliferation and cell death within a tumor. Here we have investigated a theoretical construct, whereby one of such mechanisms, the time to induction of angiogenesis, or "angiogenic switch", is mitigated by the degree of stromal stimulation by the tumor. We tested this hypothesis and its implications by introducing a mathematical model that captures how angiogenesis regulators, released from the platelet clot, contribute to formation of normal vasculature. We then modified the model to introduce tumor-induced increase in production of angiogenesis regulators and were able to simulate pathological angiogenesis. Through varying parameters governing the degree of tumor-induced stromal stimulation, we were able to qualitatively replicate experimentally observed growth curves for both dormant and actively growing tumors of breast cancer and liposarcoma. In fact, variation of very few parameters was sufficient to replicate any experimentally observed time to angiogenic switch in the available data. Finally, we investigated the effects of tighter binding isoforms of angiogenesis stimulators on neovasculature formation and tumor growth, which may provide an explanation for variations in angiogenesis -dependence in tumors of different tissue origin. PMID- 26826488 TI - A cancer treatment based on synergy between anti-angiogenic and immune cell therapies. AB - A mathematical model integrating tumor angiogenesis and tumor-targeted cytotoxicity by immune cells was developed to identify the therapeutic window of two distinct modes to treat cancer: (1) an anti-angiogenesis treatment based on the monoclonal antibody bevacizumab that targets tumor vasculature, and (2) immunotherapy involving the injection of unlicensed dendritic cells to boost the anti-tumor adaptive response. The angiogenic cytokine Vascular Endothelial Growth Factor (VEGF) contributes to the immunosuppressive tumor microenvironment, which is responsible for the short-lived therapeutic effect of cancer-targeted immunotherapy. The effect of immunosuppression on the width of the therapeutic window of each treatment was quantified. Experimental evidence has shown that neutralizing immunosuppressive cytokines results in an enhanced immune response against infections and chronic diseases. The model was used to determine treatment protocols involving the combination of anti-VEGF and unlicensed dendritic cell injections that enhance tumor regression. The model simulations predicted that the most effective method to treat tumors involves administering a series of biweekly anti-VEGF injections to disrupt angiogenic processes and limit tumor growth. The simulations also verified the hypothesis that reducing the concentration of the immunosuppressive factor VEGF prior to an injection of unlicensed dendritic cells enhances the cytotoxicity of CD8+ T cells and results in complete tumor elimination. Feasible treatment protocols for tumors that are diagnosed late and have grown to a relatively large size were identified. PMID- 26826489 TI - Evolution of genetic instability in heterogeneous tumors. AB - Genetic instability is an important characteristic of cancer. While most cancers develop genetic instability at some stage of their progression, sometimes a temporary rise of instability is followed by the return to a relatively stable genome. Neither the reasons for these dynamics, nor, more generally, the role of instability in tumor progression, are well understood. In this paper we develop a class of mathematical models to study the evolutionary competition dynamics among different sub-populations in a heterogeneous tumor. We observe that despite the complexity of this multi-component and multi-process system, there is only a small number of scenarios expected in the context of the evolution of instability. If the penalty incurred by unstable cells (the decrease in the growth due to deleterious mutations) is high compared with the gain (the production rate of advantageous mutations), then instability does not evolve. In the opposite case, instability evolves and comes to dominate the system. In the intermediate parameter regime, instability is generated but later gives way to stable clones. Moreover, the model also informs us of the patterns of instability for cancer lineages corresponding to different stages of progression. It is predicted that mutations causing instability are merely "passengers" in tumors that have undergone only a small number of malignant mutations. Further down the path of carcinogenesis, however, unstable cells are more likely to give rise to the winning clonal wave that takes over the tumor and carries the evolution forward, thus conferring a causal role of the instability in such cases. Further, each individual clonal wave (i.e. cells harboring a fixed number of malignant driver mutations) experiences its own evolutionary history. It can fall under one of three types of temporal behavior: stable throughout, unstable to stable, or unstable throughout. Which scenario is realized depends on the subtle (but predictable) interplay among mutation rates and the death toll associated with the instability. The modeling approach provided here sheds light onto important aspects of the evolutionary dynamics of instability, which may be relevant to treatment scenarios that target instability or damage repair. PMID- 26826490 TI - Urinary microRNAs as potential biomarkers of pesticide exposure. AB - MicroRNAs (miRNAs) are post-transcriptional regulators that silence messenger RNAs. Because miRNAs are stable at room temperature and long-lived, they have been proposed as molecular biomarkers to monitor disease and exposure status. While urinary miRNAs have been used clinically as potential diagnostic markers for kidney and bladder cancers and other diseases, their utility in non-clinical settings has yet to be fully developed. Our goal was to investigate the potential for urinary miRNAs to act as biomarkers of pesticide exposure and early biological response by identifying the miRNAs present in urine from 27 parent/child, farmworker/non-farmworker pairs (16FW/11NFW) collected during two agricultural seasons (thinning and post-harvest) and characterizing the between- and within-individual variability of these miRNA epigenetic regulators. MiRNAs were isolated from archived urine samples and identified using PCR arrays. Comparisons were made between age, households, season, and occupation. Of 384 miRNAs investigated, 297 (77%) were detectable in at least one sample. Seven miRNAs were detected in at least 50% of the samples, and one miRNA was present in 96% of the samples. Principal components and hierarchical clustering analyses indicate significant differences in miRNA profiles between farmworker and non farmworker adults as well as between seasons. Six miRNAs were observed to be positively associated with farmworkers status during the post-harvest season. Expression of five of these miRNA trended towards a positive dose response relationship with organophosphate pesticide metabolites in farmworkers. These results suggest that miRNAs may be novel biomarkers of pesticide exposure and early biological response. PMID- 26826491 TI - Notch signaling mediates crosstalk between endothelial cells and macrophages via Dll4 and IL6 in cardiac microvascular inflammation. AB - Although short-term outcomes have improved with modern era immunosuppression, little progress has been made in long-term graft survival in cardiac transplantation. Antibody-mediated rejection (AMR) is one of the leading causes of graft failure and contributes significantly to poor long-term outcomes. Endothelial cell (EC) injury, intravascular macrophage infiltrate and microvascular inflammation are the histological features of AMR. Nevertheless, mechanisms of AMR remain unclear and treatment is still limited. Here, we investigated the mechanisms underlying vascular and inflammatory cell network involved in AMR at endothelial and macrophage levels, using endomyocardial transplant biopsies and EC/monocyte cocultures. First, we found that AMR associates with changes in Notch signaling at endothelium/monocyte interface including loss of endothelial Notch4 and the acquisition of the Notch ligand Dll4 in both cell types. We showed that endothelial Dll4 induces macrophage polarization into a pro-inflammatory fate (CD40(high)CD64(high)CD200R(low) HLA DR(low)CD11b(low)) eliciting the production of IL-6. Dll4 and IL-6 are both Notch dependent and are required for macrophage polarization through selective down and upregulation of M2- and M1-type markers, respectively. Overall, these findings highlight the impact of the graft's endothelium on macrophage recruitment and differentiation upon AMR via Notch signaling. We identified Dll4 and IL-6 as coregulators of vascular inflammation in cardiac transplantation and as potential targets for immunotherapy. PMID- 26826493 TI - Endocarditis is Alive and Well, Unfortunately. PMID- 26826492 TI - Inhibition of sortase A by chalcone prevents Listeria monocytogenes infection. AB - The critical role of sortase A in gram-positive bacterial pathogenicity makes this protein a good potential target for antimicrobial therapy. In this study, we report for the first time the crystal structure of Listeria monocytogenes sortase A and identify the active sites that mediate its transpeptidase activity. We also used a sortase A (SrtA) enzyme activity inhibition assay, simulation, and isothermal titration calorimetry analysis to discover that chalcone, an agent with little anti-L. monocytogenes activity, could significantly inhibit sortase A activity with an IC50 of 28.41 +/- 5.34 MUM by occupying the active site of SrtA. The addition of chalcone to a co-culture of L. monocytogenes and Caco-2 cells significantly inhibited bacterial entry into the cells and L. monocytogenes mediated cytotoxicity. Additionally, chalcone treatment decreased the mortality of infected mice, the bacterial burden in target organs, and the pathological damage to L. monocytogenes-infected mice. In conclusion, these findings suggest that chalcone is a promising candidate for the development of treatment against L. monocytogenes infection. PMID- 26826494 TI - The American Journal of Medicine: Excellence in Publishing 2015. PMID- 26826495 TI - BMPs are direct triggers of interdigital programmed cell death. AB - During vertebrate embryogenesis the interdigital mesenchyme is removed by programmed cell death (PCD), except in species with webbed limbs. Although bone morphogenetic proteins (BMPs) have long been known to be players in this process, it is unclear if they play a direct role in the interdigital mesenchyme or if they only act indirectly, by affecting fibroblast growth factor (FGF) signaling. A series of genetic studies have shown that BMPs act indirectly by regulating the withdrawal of FGF activity from the apical ectodermal ridge (AER); this FGF activity acts as a cell survival factor for the underlying mesenchyme. Other studies using exogenous factors to inhibit BMP activity in explanted mouse limbs suggest that BMPs do not act directly in the mesenchyme. To address the question of whether BMPs act directly, we used an interdigit-specific Cre line to inactivate several genes that encode components of the BMP signaling pathway, without perturbing the normal downregulation of AER-FGF activity. Of three Bmps expressed in the interdigital mesenchyme, Bmp7 is necessary for PCD, but Bmp2 and Bmp4 both have redundant roles, with Bmp2 being the more prominent player. Removing BMP signals to the interdigit by deleting the receptor gene, Bmpr1a, causes a loss of PCD and syndactyly, thereby unequivocally proving that BMPs are direct triggers of PCD in this tissue. We present a model in which two events must occur for normal interdigital PCD: the presence of a BMP death trigger and the absence of an FGF survival activity. We demonstrate that neither event is required for formation of the interdigital vasculature, which is necessary for PCD. However, both events converge on the production of reactive oxygen species that activate PCD. PMID- 26826496 TI - The epigenetic modifier DNMT3A is necessary for proper otic placode formation. AB - Cranial placodes are thickenings in the ectoderm that give rise to sensory organs and peripheral ganglia of the vertebrate head. At gastrula and neurula stages, placodal precursors are intermingled in the neural plate border with future neural and neural crest cells. Here, we show that the epigenetic modifier, DNA methyl transferase (DNMT) 3A, expressed in the neural plate border region, influences development of the otic placode which will contribute to the ear. DNMT3A is expressed in the presumptive otic region at gastrula through neurula stages and later in the otic placode itself. Whereas neural plate border and non neural ectoderm markers Erni, Dlx5, Msx1 and Six1 are unaltered, DNMT3A loss of function leads to early reduction in the expression of the key otic placode specifier genes Pax2 and Gbx2 and later otic markers Sox10 and Soho1. Reduction of Gbx2 was first observed at HH7, well before loss of other otic markers. Later, this translates to significant reduction in the size of the otic vesicle. Based on these results, we propose that DNMT3A is important for enabling the activation of Gbx2 expression, necessary for normal development of the inner ear. PMID- 26826497 TI - A central to peripheral progression of cell cycle exit and hair cell differentiation in the developing mouse cristae. AB - The inner ear contains six distinct sensory organs that each maintains some ability to regenerate hair cells into adulthood. In the postnatal cochlea, there appears to be a relationship between the developmental maturity of a region and its ability to regenerate as postnatal regeneration largely occurs in the apical turn, which is the last region to differentiate and mature during development. In the mature cristae there are also regional differences in regenerative ability, which led us to hypothesize that there may be a general relationship between the relative maturity of a region and the regenerative competence of that region in all of the inner ear sensory organs. By analyzing adult mouse cristae labeled embryonically with BrdU, we found that hair cell birth starts in the central region and progresses to the periphery with age. Since the peripheral region of the adult cristae also maintains active Notch signaling and some regenerative competence, these results are consistent with the hypothesis that the last regions to develop retain some of their regenerative ability into adulthood. Further, by analyzing embryonic day 14.5 inner ears we provide evidence for a wave of hair cell birth along the longitudinal axis of the cristae from the central regions to the outer edges. Together with the data from the adult inner ears labeled with BrdU as embryos, these results suggest that hair cell differentiation closely follows cell cycle exit in the cristae, unlike in the cochlea where they are uncoupled. PMID- 26826500 TI - The Hunsruck biota: A unique window into the ecology of Lower Devonian arthropods. AB - The approximately 400-million-year old Hunsruck biota provides a unique window into Devonian marine life. Fossil evidence suggests that this biota was dominated by echinoderms and various classes of arthropods, including Trilobita, stem lineage representatives of Euarthropoda, Chelicerata and Eucrustacea, as well as several crown group Chelicerata and Eucrustacea. The Hunsruck biota's exceptional preservation allows detailed reconstructions and description of key-aspects of its fauna's functional morphologies thereby revealing modes of locomotion, sensory perception, and feeding strategies. Morphological and stratigraphic data are used for a critical interpretation of the likely habitats, mode of life and nutritional characteristics of this diverse fauna. Potential predators include pycnogonids and other chelicerates, as well as the now extinct stem arthropods Schinderhannes bartelsi, Cambronatus brasseli and Wingertshellicus backesi. Mainly the deposit feeding Trilobita, Marrellomorpha and Megacheira, such as Bundenbachiellus giganteus, represents scavengers. Possibly, opportunistic scavenging was also performed by the afore-mentioned predators. Most of the studied arthropods appear to have been adapted to living in relatively well illuminated conditions within the photic zone. Fossil evidence for associations amongst arthropods and other classes of metazoans is reported. These associations provide evidence of likely community structures. PMID- 26826498 TI - Advancing drug discovery for neuropsychiatric disorders using patient-specific stem cell models. AB - Compelling clinical, social, and economic reasons exist to innovate in the process of drug discovery for neuropsychiatric disorders. The use of patient specific, induced pluripotent stem cells (iPSCs) now affords the ability to generate neuronal cell-based models that recapitulate key aspects of human disease. In the context of neuropsychiatric disorders, where access to physiologically active and relevant cell types of the central nervous system for research is extremely limiting, iPSC-derived in vitro culture of human neurons and glial cells is transformative. Potential applications relevant to early stage drug discovery, include support of quantitative biochemistry, functional genomics, proteomics, and perhaps most notably, high-throughput and high-content chemical screening. While many phenotypes in human iPSC-derived culture systems may prove adaptable to screening formats, addressing the question of which in vitro phenotypes are ultimately relevant to disease pathophysiology and therefore more likely to yield effective pharmacological agents that are disease-modifying treatments requires careful consideration. Here, we review recent examples of studies of neuropsychiatric disorders using human stem cell models where cellular phenotypes linked to disease and functional assays have been reported. We also highlight technical advances using genome-editing technologies in iPSCs to support drug discovery efforts, including the interpretation of the functional significance of rare genetic variants of unknown significance and for the purpose of creating cell type- and pathway-selective functional reporter assays. Additionally, we evaluate the potential of in vitro stem cell models to investigate early events of disease pathogenesis, in an effort to understand the underlying molecular mechanism, including the basis of selective cell-type vulnerability, and the potential to create new cell-based diagnostics to aid in the classification of patients and subsequent selection for clinical trials. A number of key challenges remain, including the scaling of iPSC models to larger cohorts and integration with rich clinicopathological information and translation of phenotypes. Still, the overall use of iPSC-based human cell models with functional cellular and biochemical assays holds promise for supporting the discovery of next-generation neuropharmacological agents for the treatment and ultimately prevention of a range of severe mental illnesses. PMID- 26826499 TI - The role of bone sialoprotein in the tendon-bone insertion. AB - Tendons/ligaments insert into bone via a transitional structure, the enthesis, which is susceptible to injury and difficult to repair. Fibrocartilaginous entheses contain fibrocartilage in their transitional zone, part of which is mineralized. Mineral-associated proteins within this zone have not been adequately characterized. Members of the Small Integrin Binding Ligand N-linked Glycoprotein (SIBLING) family are acidic phosphoproteins expressed in mineralized tissues. Here we show that two SIBLING proteins, bone sialoprotein (BSP) and osteopontin (OPN), are present in the mouse enthesis. Histological analyses indicate that the calcified zone of the quadriceps tendon enthesis is longer in Bsp(-/-) mice, however no difference is apparent in the supraspinatus tendon enthesis. In an analysis of mineral content within the calcified zone, micro-CT and Raman spectroscopy reveal that the mineral content in the calcified fibrocartilage of the quadriceps tendon enthesis are similar between wild type and Bsp(-/-) mice. Mechanical testing of the patellar tendon shows that while the tendons fail under similar loads, the Bsp(-/-) patellar tendon is 7.5% larger in cross sectional area than wild type tendons, resulting in a 16.5% reduction in failure stress. However, Picrosirius Red staining shows no difference in collagen organization. Data collected here indicate that BSP is present in the calcified fibrocartilage of murine entheses and suggest that BSP plays a regulatory role in this structure, influencing the growth of the calcified fibrocartilage in addition to the weakening of the tendon mechanical properties. Based on the phenotype of the Bsp(-/-) mouse enthesis, and the known in vitro functional properties of the protein, BSP may be a useful therapeutic molecule in the reattachment of tendons and ligaments to bone. PMID- 26826501 TI - Risk of major bleeding in patients receiving vitamin K antagonists or low doses of aspirin. A systematic review and meta-analysis. AB - Prior meta-analysis and observational studies have suggested that the bleeding risks associated with anticoagulation using vitamin K antagonists (VKA) or aspirin (ASA) are similar. OBJECTIVE: The aim of this systematic review was to provide the odds ratios (ORs) of major bleeding, intracranial bleeding or major extra-cranial bleeding of anticoagulation with VKA compared to low doses of ASA. METHODS: We conducted a systematic review of Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (RCT). Randomized controlled trials reporting bleeding rates in adult patients randomized to a VKA (INR 2-3) or to ASA alone (<325mg daily). Random effects OR were calculated. RESULTS: Fifteen trials reporting the outcome of 2511 participants treated with VKA alone and 2471 treated with ASA alone were included; most common conditions evaluated were non-valvular atrial fibrillation (five trials) and heart failure (three trials). Overall, the use of VKA was associated with an increased risk of major bleeding (OR 1.76 (95% CI 1.33-2.33) when compared to ASA. The OR associated with VKA use for intracranial bleeding and extra-cranial bleeding were 1.74 (95% CI 0.83-3.62) and 1.66 (95% CI 0.94-2.92), respectively. In trials achieving good control of anticoagulation [time in therapeutic range (TTR) >65%], the risk of bleeding with VKA was similar to that of ASA [OR 1.16 (95% CI 0.79-1.71)]. CONCLUSION: Contrary to prior reports our results suggest that the risk of major bleeding with the use VKA is higher compared to those of patients treated with ASA alone. However, in patients achieving a good TTR, the risk of major bleeding with VKA or ASA is similar. PMID- 26826502 TI - Losartan and captopril treatment rescue normal thrombus formation in microfibril associated glycoprotein-1 (MAGP1) deficient mice. AB - INTRODUCTION: MAGP1 is a glycoprotein present in the elastic fibers and is a part of the microfibrils components. MAGP1 interacts with von Willebrand factor and the active form of TGF-beta and BMP. In mice lacking MAGP1, thrombus formation is delayed, increasing the occlusion time of carotid artery despite presenting normal blood coagulation in vitro. MAGP1-containing microfibrils may play a role in hemostasis and thrombosis. In this work, we evaluated the function of MAGP1 and its relation to TGF-beta in the arterial thrombosis process. METHODS AND RESULTS: We analyzed thrombus formation time in wild type and MAGP1-deficient mice comparing Rose Bengal and Ferric Chloride induced arterial lesion. The potential participation of TGF-beta in this process was accessed when we treated both wild type and MAGP1-deficient mice with losartan (an antihypertensive drug that decreases TGF-beta activity) or captopril (an angiotensin converting enzyme inhibitor that was used as a control antihypertensive drug). Besides, we evaluated thrombus embolization and the gelatinolytic activity in the arterial walls in vitro and ex vivo. Losartan and captopril were able to recover the thrombus formation time without changing blood pressure, activated partial thromboplastin time (aPTT), PT (prothrombin time), platelet aggregation and adhesion, but decreased gelatinase activity. CONCLUSIONS: Our results suggest that both treatments are effective in the prevention of the sub-endothelial ECM degradation, allowing the recovery of normal thrombus formation. PMID- 26826503 TI - The role of inflammation in post-thrombotic syndrome after pregnancy-related deep vein thrombosis: A population-based, cross-sectional study. AB - Previous studies suggest that inflammation may play a role in the pathophysiology of post-thrombotic syndrome (PTS). The aims of the present study were to evaluate markers of inflammation as possible predictors for PTS after pregnancy-related deep vein thrombosis (DVT). We included 182 women with a pregnancy-related DVT during 1990-2003 and 314 controls. All women answered a questionnaire and donated a blood sample in 2006. PTS was diagnosed when a self-reported Villalta score was above 4. The following predictors of PTS were included: high sensitivity C reactive protein (hsCRP), interleukin (IL)-6, IL-8, IL-10, monocyte chemotactic protein (MCP)-1, transforming growth factor (TGF)-beta1, platelet derived growth factor (PDGF)-BB, and the two adhesion molecules intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1. High values were defined as above median value among controls. We found that 41% of cases were diagnosed with PTS 3-16years after index pregnancy. In univariate analyses, high values of hsCRP, IL-6, and IL-10 were significantly associated with PTS with ORs 2.3 (95% CI; 1.2-4.2, p=0.008), 1.9 (1.0-3.5, p=0.04), and 10.8 (1.3-89.8, p=0.01), respectively. Only hsCRP, which has previously been found to be independently associated with PTS, was independently associated with PTS in a multivariate logistic regression model, when adjusting for proximal DVT occurring postpartum, age above 33years, and smoking (adjusted OR 2.4; 95% CI 1.2-4.8, p=0.01). We conclude that hsCRP was associated with PTS 3-16years after pregnancy-related DVT. PMID- 26826504 TI - Dabigatran but not rivaroxaban or apixaban treatment decreases fibrinolytic resistance in patients with atrial fibrillation. AB - INTRODUCTION: Most anticoagulants stimulate fibrinolysis in vitro through mechanisms dependent on and independent of thrombin activatable fibrinolysis inhibitor (TAFI). We evaluated the effect of dabigatran, rivaroxaban and apixaban treatment on plasma fibrinolysis in patients with non-valvular atrial fibrillation. METHODS AND RESULTS: Patients treated with dabigatran etexilate (n=22), rivaroxaban (n=24) or apixaban (n=22) were studied. Plasma was obtained before (trough) and 2h after drug intake (peak). Fibrinolytic resistance of clots exposed to exogenous tissue plasminogen activator was significantly lower in peak than in trough samples and correlated with drug concentration only in dabigatran group. Moreover, fibrinolytic resistance at peak was lower in dabigatran than in rivaroxaban and apixaban groups. This difference disappeared if the TAFI pathway was inhibited. Thrombin generation and TAFI activation were markedly lower in peak than in trough samples in all three groups. However, TAFIa levels in trough and peak samples were significantly lower in dabigatran group than in rivaroxaban and apixaban groups. Circulating levels of prothrombin fragment F1+2 (reflecting in vivo thrombin generation) and plasmin-antiplasmin complex (reflecting plasmin generation) were not or barely influenced by drug levels in all groups. CONCLUSIONS: Our data suggest that dabigatran, contrary to rivaroxaban and apixaban, reduces fibrinolytic resistance by virtue of its greater impact on TAFI activation. The profibrinolytic effect of dabigatran may play a role locally, at sites of fibrin formation, by making the nascent thrombus more susceptible to plasminogen-dependent degradation. PMID- 26826505 TI - Downregulation of let-7e-5p contributes to endothelial progenitor cell dysfunction in deep vein thrombosis via targeting FASLG. AB - This study aimed to evaluate the role of let-7e-5p in endothelial progenitor cells (EPCs) function and explore its therapeutic potential for deep vein thrombosis (DVT). We performed miRNAs screening and found that let-7e-5p was downregulated in DVT patients compared to control subjects. By using let-7e-5p agomir and antagomir, we demonstrated that let-7e-5p increased the migration and tube formation of human and rat EPCs. Based on bioinformatics, luciferase reporter assay and gene expression analysis, we identified Fas ligand (FASLG) as the target of let-7e-5p, and FASLG knockdown increased the migration and tube formation of EPCs. Furthermore, EPCs overexpressing let-7e-5p exhibited enhanced ability of homing and thrombus revascularization inrat model of venous thrombosis. In conclusion, let-7e-5p regulates the function of EPCs and is a potential therapeutic target in DVT treatment. PMID- 26826506 TI - Early thromboembolic events <=1week after fast-track total hip and knee arthroplasty. AB - INTRODUCTION: Thromboembolic events (TEE) are serious complications after total hip (THA) and knee arthroplasty (TKA), with reported in-hospital incidences of about 0.5-1% for venous thromboembolic events (VTE) and 0.2% for myocardial infarctions (MI) and stroke. However, little data exist on in-hospital TEE when using a standardized fast-track protocol with early mobilization. MATERIALS AND METHODS: A large detailed cohort study in primary unilateral THA and TKAs on "early" (in-hospital or after discharge but within 1week of surgery) and 30-days TEEs, including prospective recording of patient characteristics, complete follow up through the Danish National Patient Register, and detailed evaluation on disposing factors and consequences of "early" TEEs through review of medical records. RESULTS: In 13,775 procedures with a median LOS of 2days, 43 (0.32%; 95% CI: 0.23-0.42) "early" and 90 (0.65%; 95% CI: 0.53-0.80) 30-day TEEs were recorded. "Early" TEEs consisted of 9 (0.07%; 95% CI: 0.04-0.13) MI, 10 (0.08% 95% CI: 0.04-0.13) strokes, 13 (0.09%; 95% CI: 0.05-0.16) pulmonary embolisms and 11 (0.08%; 95% CI: 0.04-0.15) deep venous thromboses. Most TEEs were in patients with irreversible dispositions (e.g. previous TEE, high age and cardiac disease), but 5 of 9 MIs were associated with postoperative anemia. All in-hospital VTE (n: 16) occurred while patients received recommended thromboprophylaxis. CONCLUSIONS: Incidence of "early" TEEs after fast-track THA and THA is low, but MIs may be further reduced by improving perioperative treatment of anemia. Further research is needed regarding interventions for prevention of "early" TEE in disposed patients. PMID- 26826507 TI - Platelet reactivity in twin pregnancies. AB - BACKGROUND: Gestational thrombocytopenia is more likely to occur in twin than singleton pregnancies. However, it is unclear whether platelets are more reactive in twin than singleton pregnancies. METHODS: Changes in spontaneous platelet aggregation and concomitant fall in platelet count were examined over 90min after blood sampling in 171 and 52 citrated whole blood (CWB) samples from 59 and 17 women with singleton and twin pregnancies, respectively. Soluble P-selectin (sP selectin) levels in the plasma were also determined. RESULTS: CWB 60min after blood sampling during 2nd trimester exhibited significantly larger numbers of platelet aggregates (1297+/-1600 vs. 497+/-432/MUl, P=0.040) concomitant with significantly greater net decrease in platelet count (152+/-55 vs. 115+/ 45*10(9)/MUl, P=0.036) in twin than singleton pregnancies, respectively. This was followed by significantly lower 3rd trimester platelet count (181+/-43 vs. 229+/ 62*10(9)/l, P=0.009) with significantly greater mean platelet volume (8.0+/-1.2 vs. 7.1+/-1.1fl, P=0.021) in twin than singleton pregnancies, respectively. The 3rd trimester sP-selectin per platelet was significantly higher in twin than singleton pregnancies. CONCLUSIONS: Platelets were more reactive in the 2nd trimester of twin than singleton pregnancies. This enhanced platelet reactivity may explain the decreased platelet count in the 3rd trimester of twin pregnancy. PMID- 26826509 TI - Cardiovascular disease and mortality after a first episode of venous thromboembolism in young and middle-aged women. AB - BACKGROUND: Patients with a history of venous thromboembolism (VTE) seem to have an increased risk of arterial cardiovascular disease (CVD). OBJECTIVES: To evaluate the risk of CVD and overall mortality after a first episode of VTE in women and to assess common risk factors for VTE and CVD. PATIENTS/METHODS: We performed a cohort study inviting 1433 women with a previous VTE (exposed) and 1402 women without VTE (unexposed). The cohort was derived from TEHS, a Swedish population-based case-control study on risk factors for VTE in women age 18 64years. The women were recruited in 2002-2009. During 2011 information on CVD and mortality was obtained from a questionnaire and from the Swedish Patient Register and the Cause of Death Register. Hazard ratios (HR) for CVD and their 95% confidence intervals (CI) were calculated using Cox regression. In multivariate analyses we adjusted for age, smoking, diabetes mellitus, hypertension and body mass index. RESULTS: 2108 (75%) women (mean age 47+/ 13years) accepted participation. During the total follow up of 11,920 person years 35 (3.2%, 95% CI 0.7-2.1) among the exposed and 14 (1.4%, 95% CI 0.2-4.3) among the unexposed had any CVD event. The adjusted HR for CVD was 2.0 (95% CI 1.1-3.9) the adjusted HR for mortality was 2.3 (95% CI 1.2-4.6) CONCLUSION: Women with a previous VTE had a two-fold increased risk of CVD and overall mortality. Adjusting for cardiovascular risk factors only modestly changed the estimates. PMID- 26826508 TI - Association between high on-treatment platelet reactivity and occurrence of cerebral ischemic events in patients undergoing percutaneous coronary intervention. AB - INTRODUCTION: Percutaneous coronary angioplasty (PCI) has become a routine treatment in symptomatic patients with coronary artery disease. The use of new generation drug eluting stents (DES) and dual antiplatelet therapy has significantly improved treatment outcomes and increased patients' safety by reducing the risk of stent thrombosis. AIMS: The goal of this study was to assess whether high on treatment platelet reactivity (HTPR), despite clopidogrel treatment, measured with Multiplate Electrode Aggregometer (MEA) is associated with the risk of adverse ischemic cerebral events. METHODS: Symptomatic patients with coronary artery disease admitted for coronary angiography and angioplasty (PCI) were consecutively enrolled in this study. 249 consecutive patients underwent coronary artery stenting for stable angina (n=215) or non-ST-elevation acute coronary syndrome (n=34). Inhibition of platelet aggregation was assessed by MEA. Genetic polymorphism of CYP2C19 was tested by HRM Real-Time PCR method in 150 patients. RESULTS: Patients with HTPR were more frequently diagnosed with ischemic stroke (p=0.0351, OR=16.818, 95% CI [1.464-193.23]) and other ischemic cerebral events (stroke or TIA, p=0.0339, OR=6.5, 95% CI [1.36-31.07]). Cumulative assessment of all ischemic and hemorrhagic events showed no statistical significance. Cerebral ischemic event was the only adverse event that correlated with CYP2C19 (*2/*2) allele (p=0.0489, OR=10; 95% CI [1.39-71.80]). CONCLUSIONS: HTPR assessed by MEA, in patients treated with clopidogrel after coronary artery stenting was found to be an important risk factor of ischemic cerebral events. In concordance, the carriers of CYP2C19*2/*2 allele showed an increased rate of ischemic cerebral events. PMID- 26826510 TI - Metabolic engineering with multi-objective optimization of kinetic models. AB - Kinetic models have a great potential for metabolic engineering applications. They can be used for testing which genetic and regulatory modifications can increase the production of metabolites of interest, while simultaneously monitoring other key functions of the host organism. This work presents a methodology for increasing productivity in biotechnological processes exploiting dynamic models. It uses multi-objective dynamic optimization to identify the combination of targets (enzymatic modifications) and the degree of up- or down regulation that must be performed in order to optimize a set of pre-defined performance metrics subject to process constraints. The capabilities of the approach are demonstrated on a realistic and computationally challenging application: a large-scale metabolic model of Chinese Hamster Ovary cells (CHO), which are used for antibody production in a fed-batch process. The proposed methodology manages to provide a sustained and robust growth in CHO cells, increasing productivity while simultaneously increasing biomass production, product titer, and keeping the concentrations of lactate and ammonia at low values. The approach presented here can be used for optimizing metabolic models by finding the best combination of targets and their optimal level of up/down regulation. Furthermore, it can accommodate additional trade-offs and constraints with great flexibility. PMID- 26826511 TI - Binge drinking impacts dorsal striatal response during decision making in adolescents. AB - Adolescence is a time of both increased risk taking and increased vulnerability to the neurotoxic effects of alcohol. However, it is unclear whether brain functioning abnormalities in adolescent binge drinkers are a result of alcohol use itself or whether they represent premorbid risk characteristics. The current study addresses this question by using a modified version of the Wheel of Fortune (WOF) task, during functional magnetic resonance imaging (fMRI), at both baseline, while all subjects were alcohol-naive, and revisit, when half of the subjects had emerged into regular binge drinking (n=13) and half remained alcohol and substance-naive (n=13). Region of interest (ROI) analysis revealed that during decision making, there was a significant binge-drinking related reduction in brain activation in the dorsal striatum, an effect associated with degree of recent use. Furthermore, whole-brain analysis revealed a decrease in fronto parietal brain activation prior to initiation of alcohol use, in adolescents who went on to binge drink. Additionally, there were numerous regions, both cortical and subcortical, in which there was a significant time-related developmental change, across groups. These results demonstrate how abnormalities in decision making related circuitry might both lead to and perpetuate alcohol drinking behavior. These findings help aid in our ability to disentangle consequences of binge drinking from potential risk markers for future binge drinking, and may help guide future prevention and intervention strategies. PMID- 26826512 TI - Bingham-NODDI: Mapping anisotropic orientation dispersion of neurites using diffusion MRI. AB - This paper presents Bingham-NODDI, a clinically-feasible technique for estimating the anisotropic orientation dispersion of neurites. Direct quantification of neurite morphology on clinical scanners was recently realised by a diffusion MRI technique known as neurite orientation dispersion and density imaging (NODDI). However in its current form NODDI cannot estimate anisotropic orientation dispersion, which is widespread in the brain due to common fanning and bending of neurites. This work proposes Bingham-NODDI that extends the NODDI formalism to address this limitation. Bingham-NODDI characterises anisotropic orientation dispersion by utilising the Bingham distribution to model neurite orientation distribution. The new model estimates the extent of dispersion about the dominant orientation, separately along the primary and secondary dispersion orientations. These estimates are subsequently used to estimate the overall dispersion about the dominant orientation and the dispersion anisotropy. We systematically evaluate the ability of the new model to recover these key parameters of anisotropic orientation dispersion with standard NODDI protocol, both in silico and in vivo. The results demonstrate that the parameters of the proposed model can be estimated without additional acquisition requirements over the standard NODDI protocol. Thus anisotropic dispersion can be determined and has the potential to be used as a marker for normal brain development and ageing or in pathology. We additionally find that the original NODDI model is robust to the effects of anisotropic orientation dispersion, when the quantification of anisotropic dispersion is not of interest. PMID- 26826515 TI - Brain-based decoding of mentally imagined film clips and sounds reveals experience-based information patterns in film professionals. AB - In the perceptual domain, it has been shown that the human brain is strongly shaped through experience, leading to expertise in highly-skilled professionals. What has remained unclear is whether specialization also shapes brain networks underlying mental imagery. In our fMRI study, we aimed to uncover modality specific mental imagery specialization of film experts. Using multi-voxel pattern analysis we decoded from brain activity of professional cinematographers and sound designers whether they were imagining sounds or images of particular film clips. In each expert group distinct multi-voxel patterns, specific for the modality of their expertise, were found during classification of imagery modality. These patterns were mainly localized in the occipito-temporal and parietal cortex for cinematographers and in the auditory cortex for sound designers. We also found generalized patterns across perception and imagery that were distinct for the two expert groups: they involved frontal cortex for the cinematographers and temporal cortex for the sound designers. Notably, the mental representations of film clips and sounds of cinematographers contained information that went beyond modality-specificity. We were able to successfully decode the implicit presence of film genre from brain activity during mental imagery in cinematographers. The results extend existing neuroimaging literature on expertise into the domain of mental imagery and show that experience in visual versus auditory imagery can alter the representation of information in modality specific association cortices. PMID- 26826513 TI - Face-selective regions differ in their ability to classify facial expressions. AB - Recognition of facial expressions is crucial for effective social interactions. Yet, the extent to which the various face-selective regions in the human brain classify different facial expressions remains unclear. We used functional magnetic resonance imaging (fMRI) and support vector machine pattern classification analysis to determine how well face-selective brain regions are able to decode different categories of facial expression. Subjects participated in a slow event-related fMRI experiment in which they were shown 32 face pictures, portraying four different expressions: neutral, fearful, angry, and happy and belonging to eight different identities. Our results showed that only the amygdala and the posterior superior temporal sulcus (STS) were able to accurately discriminate between these expressions, albeit in different ways: the amygdala discriminated fearful faces from non-fearful faces, whereas STS discriminated neutral from emotional (fearful, angry and happy) faces. In contrast to these findings on the classification of emotional expression, only the fusiform face area (FFA) and anterior inferior temporal cortex (aIT) could discriminate among the various facial identities. Further, the amygdala and STS were better than FFA and aIT at classifying expression, while FFA and aIT were better than the amygdala and STS at classifying identity. Taken together, our findings indicate that the decoding of facial emotion and facial identity occurs in different neural substrates: the amygdala and STS for the former and FFA and aIT for the latter. PMID- 26826514 TI - Including diffusion time dependence in the extra-axonal space improves in vivo estimates of axonal diameter and density in human white matter. AB - Axonal density and diameter are two fundamental properties of brain white matter. Recently, advanced diffusion MRI techniques have made these two parameters accessible in vivo. However, the techniques available to estimate such parameters are still under development. For example, current methods to map axonal diameters capture relative trends over different structures, but consistently over-estimate absolute diameters. Axonal density estimates are more accessible experimentally, but different modeling approaches exist and the impact of the experimental parameters has not been thoroughly quantified, potentially leading to incompatibility of results obtained in different studies using different techniques. Here, we characterise the impact of diffusion time on axonal density and diameter estimates using Monte Carlo simulations and STEAM diffusion MRI at 7 T on 9 healthy volunteers. We show that axonal density and diameter estimates strongly depend on diffusion time, with diameters almost invariably overestimated and density both over and underestimated for some commonly used models. Crucially, we also demonstrate that these biases are reduced when the model accounts for diffusion time dependency in the extra-axonal space. For axonal density estimates, both upward and downward bias in different situations are removed by modeling extra-axonal time-dependence, showing increased accuracy in these estimates. For axonal diameter estimates, we report increased accuracy in ground truth simulations and axonal diameter estimates decreased away from high values given by earlier models and towards known values in the human corpus callosum when modeling extra-axonal time-dependence. Axonal diameter feasibility under both advanced and clinical settings is discussed in the light of the proposed advances. PMID- 26826516 TI - Automatic EEG-assisted retrospective motion correction for fMRI (aE-REMCOR). AB - Head motions during functional magnetic resonance imaging (fMRI) impair fMRI data quality and introduce systematic artifacts that can affect interpretation of fMRI results. Electroencephalography (EEG) recordings performed simultaneously with fMRI provide high-temporal-resolution information about ongoing brain activity as well as head movements. Recently, an EEG-assisted retrospective motion correction (E-REMCOR) method was introduced. E-REMCOR utilizes EEG motion artifacts to correct the effects of head movements in simultaneously acquired fMRI data on a slice-by-slice basis. While E-REMCOR is an efficient motion correction approach, it involves an independent component analysis (ICA) of the EEG data and identification of motion-related ICs. Here we report an automated implementation of E-REMCOR, referred to as aE-REMCOR, which we developed to facilitate the application of E-REMCOR in large-scale EEG-fMRI studies. The aE-REMCOR algorithm, implemented in MATLAB, enables an automated preprocessing of the EEG data, an ICA decomposition, and, importantly, an automatic identification of motion-related ICs. aE-REMCOR has been used to perform retrospective motion correction for 305 fMRI datasets from 16 subjects, who participated in EEG-fMRI experiments conducted on a 3T MRI scanner. Performance of aE-REMCOR has been evaluated based on improvement in temporal signal-to-noise ratio (TSNR) of the fMRI data, as well as correction efficiency defined in terms of spike reduction in fMRI motion parameters. The results show that aE-REMCOR is capable of substantially reducing head motion artifacts in fMRI data. In particular, when there are significant rapid head movements during the scan, a large TSNR improvement and high correction efficiency can be achieved. Depending on a subject's motion, an average TSNR improvement over the brain upon the application of aE-REMCOR can be as high as 27%, with top ten percent of the TSNR improvement values exceeding 55%. The average correction efficiency over the 305 fMRI scans is 18% and the largest achieved efficiency is 71%. The utility of aE-REMCOR on the resting state fMRI connectivity of the default mode network is also examined. The motion induced position-dependent error in the DMN connectivity analysis is shown to be reduced when aE-REMCOR is utilized. These results demonstrate that aE-REMCOR can be conveniently and efficiently used to improve fMRI motion correction in large clinical EEG-fMRI studies. PMID- 26826517 TI - Human habenula segmentation using myelin content. AB - The habenula consists of a pair of small epithalamic nuclei located adjacent to the dorsomedial thalamus. Despite increasing interest in imaging the habenula due to its critical role in mediating subcortical reward circuitry, in vivo neuroimaging research targeting the human habenula has been limited by its small size and low anatomical contrast. In this work, we have developed an objective semi-automated habenula segmentation scheme consisting of histogram-based thresholding, region growing, geometric constraints, and partial volume estimation steps. This segmentation scheme was designed around in vivo 3 T myelin sensitive images, generated by taking the ratio of high-resolution T1w over T2w images. Due to the high myelin content of the habenula, the contrast-to-noise ratio with the thalamus in the in vivo 3T myelin-sensitive images was significantly higher than the T1w or T2w images alone. In addition, in vivo 7 T myelin-sensitive images (T1w over T2*w ratio images) and ex vivo proton density weighted images, along with histological evidence from the literature, strongly corroborated the in vivo 3 T habenula myelin contrast used in the proposed segmentation scheme. The proposed segmentation scheme represents a step toward a scalable approach for objective segmentation of the habenula suitable for both morphological evaluation and habenula seed region selection in functional and diffusion MRI applications. PMID- 26826518 TI - Genomic dissection of Australian Bordetella pertussis isolates from the 2008-2012 epidemic. AB - OBJECTIVES: Despite high pertussis vaccination coverage, Australia experienced a prolonged epidemic in 2008-2012. The predominant Bordetella pertussis genotype harboured pertussis toxin promoter allele, ptxP3, and pertactin gene allele, prn2. The emergence and expansion of prn non-expressing isolates (Prn negative), were also observed. We aimed to investigate the microevolution and genomic diversity of epidemic B. pertussis isolates. METHODS: We sequenced 22 B. pertussis isolates collected in 2008-2012 from two states of Australia which are geographically widely separated. Ten of the 22 were Prn negative isolates with three different modes of silencing of prn (prn::IS481F, prn::IS481R and prn::IS1002). Five pre-epidemic isolates were also sequenced for comparison. RESULTS: Five single nucleotide polymorphisms were common in the epidemic isolates and differentiated them from pre-epidemic isolates. The Australian epidemic isolates can be divided into five lineages (EL1-EL5) with EL1 containing only Prn negative isolates. Comparison with global isolates showed that three lineages remained geographically and temporally distinct whereas two lineages mixed with isolates from 2012 UK outbreak. CONCLUSION: Our results suggest significant diversification and the microevolution of B. pertussis within the 2008-2012 Australian epidemic. PMID- 26826519 TI - Understanding the true burden and infection dynamics of Bordetella pertussis using molecular diagnostics. PMID- 26826520 TI - Emotion processing fails to modulate putative mirror neuron response to trained visuomotor associations. AB - Recent neuroimaging studies have demonstrated that activation of the putative human mirror neuron system (MNS) can be elicited via visuomotor training. This is generally interpreted as supporting an associative learning account of the mirror neuron system (MNS) that argues against the ontogeny of the MNS to be an evolutionary adaptation for social cognition. The current study assessed whether a central component of social cognition, emotion processing, would influence the MNS activity to trained visuomotor associations, which could support a broader role of the MNS in social cognition. Using functional magnetic resonance imaging (fMRI), we assessed repetition suppression to the presentation of stimulus pairs involving a simple hand action and a geometric shape that was either congruent or incongruent with earlier association training. Each pair was preceded by an image of positive, negative, or neutral emotionality. In support of an associative learning account of the MNS, repetition suppression was greater for trained pairs compared with untrained pairs in several regions, primarily supplementary motor area (SMA) and right inferior frontal gyrus (rIFG). This response, however, was not modulated by the valence of the emotional images. These findings argue against a fundamental role of emotion processing in the mirror neuron response, and are inconsistent with theoretical accounts linking mirror neurons to social cognition. PMID- 26826521 TI - Introduction to the special issue on functional selectivity in perceptual and cognitive systems--a tribute to Shlomo Bentin (1946-2012). PMID- 26826524 TI - Telocyte's contacts. AB - Telocytes (TC) are an interstitial cell type located in the connective tissue of many organs of humans and laboratory mammals. By means of homocellular contacts, TC build a scaffold whose meshes integrity and continuity are guaranteed by those contacts having a mechanical function; those contacts acting as sites of intercellular communication allow exchanging information and spreading signals. Heterocellular contacts between TC and a great variety of cell types give origin to mixed networks. TC, by means of all these types of contacts, their interaction with the extracellular matrix and their vicinity to nerve endings, are part of an integrated system playing tissue/organ-specific roles. PMID- 26826523 TI - The role of IL-11 in immunity and cancer. AB - Interleukin-11 (IL-11) is a member of the glycoprotein-130 (GP-130) cytokines that utilizes the GP-130 signaling pathway shared by other cytokines of the same family. Traditionally regarded as an anti-inflammatory cytokine, IL-11 also demonstrates its role as a proinflammatory cytokine, suggesting its complex role in immune response. In recent years, IL-11 has an emerging role in various inflammation-associated cancers. In this review, we aim to discuss IL-11 signaling pathway, to explore the role of IL-11 in immunity and various cancers, and to provide a therapeutic perspective of strategies utilized to interfere IL 11 signaling in cancer cells. PMID- 26826522 TI - Interactions between space and effectiveness in human multisensory performance. AB - Several stimulus factors are important in multisensory integration, including the spatial and temporal relationships of the paired stimuli as well as their effectiveness. Changes in these factors have been shown to dramatically change the nature and magnitude of multisensory interactions. Typically, these factors are considered in isolation, although there is a growing appreciation for the fact that they are likely to be strongly interrelated. Here, we examined interactions between two of these factors - spatial location and effectiveness - in dictating performance in the localization of an audiovisual target. A psychophysical experiment was conducted in which participants reported the perceived location of visual flashes and auditory noise bursts presented alone and in combination. Stimuli were presented at four spatial locations relative to fixation (0 degrees , 30 degrees , 60 degrees , 90 degrees ) and at two intensity levels (high, low). Multisensory combinations were always spatially coincident and of the matching intensity (high-high or low-low). In responding to visual stimuli alone, localization accuracy decreased and response times (RTs) increased as stimuli were presented at more eccentric locations. In responding to auditory stimuli, performance was poorest at the 30 degrees and 60 degrees locations. For both visual and auditory stimuli, accuracy was greater and RTs were faster for more intense stimuli. For responses to visual-auditory stimulus combinations, performance enhancements were found at locations in which the unisensory performance was lowest, results concordant with the concept of inverse effectiveness. RTs for these multisensory presentations frequently violated race model predictions, implying integration of these inputs, and a significant location-by-intensity interaction was observed. Performance gains under multisensory conditions were larger as stimuli were positioned at more peripheral locations, and this increase was most pronounced for the low-intensity conditions. These results provide strong support that the effects of stimulus location and effectiveness on multisensory integration are interdependent, with both contributing to the overall effectiveness of the stimuli in driving the resultant multisensory response. PMID- 26826526 TI - Behaviour of telocytes during physiopathological activation. AB - We consider CD34+ stromal cells/telocytes (CD34+ SC/TCs) in normal and pathological conditions. These cells are involved in organisation and control of the extracellular matrix, structural support, creation of microenvironments, intercellular communication, neurotransmission, immunomodulation and immunosurveillance, inhibition of apoptosis, and control, regulation and source of other cell types. CD34+ SC/TCs are widely reported in the origin of interstitial cells of Cajal and in regeneration in the heart, skeletal muscle, skin, respiratory tree, liver, urinary system and the eye. In addition, we contribute CD34+ SC/TC hyperplasia associated with several processes, including neurogenous hyperplasia (neuroma of the appendix), hyperplasia of Leydig cells in undescended testes (Cryptorchidism), peripheral areas of inflammatory/repair processes (pericicatricial tissue and transitional zones between diseased segments in Crohn's disease and normal bowel), benign tumours (neurofibromas, Antoni-B zones of neurilemmomas, granular cell tumours, and melanocytic nevi) and in some lesions with myxoid, oedematous and degenerative changes (Reinke's oedema, myxomatous mitral valve degeneration, thyroid-associated ophthalmopathy and basophilic degenerative changes of the collagen in the dermis). We pay particular attention to the role of CD34+ SC/TCs during repair through granulation tissue, including morphologic changes, loss of CD34 expression and gain of alphaSMA expression with myofibroblast transformation, and interactions with pericytes, endothelial and inflammatory cells. Finally, we consider CD34 or alphaSMA expression in stromal cells of malignant epithelial tumours, and the role of CD34+ SC/TCs in the origin of carcinoma-associated fibroblasts (CAFs) and myofibroblasts. In conclusion, CD34+ SC/TCs play an important role in the maintenance and modulation of tissue homeostasis and in morphogenesis/renewal/repair. PMID- 26826525 TI - Telocytes in cardiac regeneration and repair. AB - Telocytes (TCs) are a novel type of stromal cells reported by Popescu's group in 2010. The unique feature that distinguishes TCs from other "classical" stromal cells is their extremely long and thin telopodes (Tps). As evidenced by electron microscopy, TCs are widely distributed in almost all tissues and organs. TCs contribute to form a three-dimensional interstitial network and play as active regulators in intercellular communication via homocellular/heterocellular junctions or shed vesicles. Interestingly, increasing evidence suggests the potential role of TCs in regenerative medicine. Although the heart retains some limited endogenous regenerative capacity, cardiac regenerative and repair response is however insufficient to make up the loss of cardiomyocytes upon injury. Developing novel strategies to increase cardiomyocyte renewal and repair is of great importance for the treatment of cardiac diseases. In this review, we focus on the role of TCs in cardiac regeneration and repair. We particularly describe the intercellular communication between TCs and cardiomyocytes, stem/progenitor cells, endothelial cells, and fibroblasts. Also, we discuss the current knowledge about TCs in cardiac repair after myocardial injury, as well as their potential roles in cardiac development and aging. TC-based therapy or TC derived exosome delivery might be used as novel therapeutic strategies to promote cardiac regeneration and repair. PMID- 26826527 TI - How much sugar do consumers add to plain yogurts? Insights from a study examining French consumer behavior and self-reported habits. AB - In France, 50% of consumers sweeten plain yogurts prior to consumption. This study measured how much sugar consumers added under contextualized testing conditions. Participants (199 French adults who regularly consume plain yogurt adding sugar) were given a plain yogurt (125 g) at the end of a full meal and were allowed to sweeten it with their usual sweetener (caster sugar, honey, or jam). The quantities added were measured indirectly by weighing the sweetener containers before and after use; they were then converted into equivalent quantities of sucrose, or "added sugar." Participants were asked to describe their relative hunger, thirst, and liking for plain yogurt and to estimate the quantity of sweetener they had added. On average, participants added 13.6 g of sugar to their yogurts, which is higher than the 10.2 g of sugar contained in pre sweetened commercial yogurts (125 g). More sugar was added when subjects used jam (24.4 g/yogurt, n = 36) as opposed to caster sugar (11.0 g/yogurt, n = 134) or honey (12.1 g/yogurt, n = 29). Age, socio-professional category, and BMI had a significant influence on added-sugar quantity. Based on behavior and attitude, participants could be separated into three evenly sized groups: "low sugar users" (n = 67, median = 6.1 g/yogurt), who tended to control their food intake, "medium sugar users" (n = 66, median = 11.4 g/yogurt), and "heavy sugar users" (n = 66, median = 19.9 g/yogurt) who sought immediate satisfaction. To our knowledge, this study is the first to provide robust data on the amount of sugar consumers add to plain yogurts in contextualized conditions (self preparation during a real meal). Our findings show that consumers underestimated by half the quantity of sweetener they added. PMID- 26826528 TI - The effect of terminal sterilization on the material properties and in vivo remodeling of a porcine dermal biologic scaffold. AB - Biologic scaffolds composed of extracellular matrix are commonly used in a variety of surgical procedures. The Food and Drug Administration typically regulates biologic scaffolds as medical devices, thus requiring terminal sterilization prior to clinical use. However, to date, no consensus exists for the most effective yet minimally destructive sterilization protocol for biologic scaffold materials. The objective of the present study was to characterize the effect of ethylene oxide, gamma irradiation and electron beam (e-beam) irradiation on the material properties and the elicited in vivo remodeling response of a porcine dermal biologic scaffold. Outcome measures included biochemical, structural, and mechanical properties as well as cytocompatibility in vitro. In vivo evaluation utilized a rodent model to examine the host response to the materials following 7, 14, and 35 days. The host response to each experimental group was determined by quantitative histologic methods and by immunolabeling for macrophage polarization (M1/M2). In vitro results show that increasing irradiation dosage resulted in a dose dependent decrease in mechanical properties compared to untreated controls. Ethylene oxide-treated porcine dermal ECM resulted in decreased DNA content, extractable total protein, and bFGF content compared to untreated controls. All ETO treated, gamma irradiated, and e beam irradiated samples had similar cytocompatibility scores in vitro. However, in vivo results showed that increasing dosages of e-beam and gamma irradiation elicited an increased rate of degradation of the biologic scaffold material following 35 days. STATEMENT OF SIGNIFICANCE: The FDA typically regulates biologic scaffolds derived from mammalian tissues as medical devices, thus requiring terminal sterilization prior to clinical use. However, there is little data and no consensus for the most effective yet minimally destructive sterilization protocol for such materials. The present study characterized the effect of common sterilization methods: ethylene oxide, gamma irradiation and electron beam irradiation on the material properties and the elicited in vivo remodeling response of a porcine dermal biologic scaffold. The results of the study will aid in the meaningful selection of sterilization methods for biologic scaffold materials. PMID- 26826529 TI - Nanofibrous spongy microspheres for the delivery of hypoxia-primed human dental pulp stem cells to regenerate vascularized dental pulp. AB - Dental pulp infection and necrosis are widespread diseases. Conventional endodontic treatments result in a devitalized and weakened tooth. In this work, we synthesized novel star-shaped polymer to self-assemble into unique nanofibrous spongy microspheres (NF-SMS), which were used to carry human dental pulp stem cells (hDPSCs) into the pulp cavity to regenerate living dental pulp tissues. It was found that NF-SMS significantly enhanced hDPSCs attachment, proliferation, odontogenic differentiation and angiogenesis, as compared to control cell carriers. Additionally, NF-SMS promoted vascular endothelial growth factor (VEGF) expression of hDPSCs in a 3D hypoxic culture. Hypoxia-primed hDPSCs/NF-SMS complexes were injected into the cleaned pulp cavities of rabbit molars for subcutaneous implantation in mice. After 4 weeks, the hypoxia group significantly enhanced angiogenesis inside the pulp chamber and promoted the formation of ondontoblast-like cells lining along the dentin-pulp interface, as compared to the control groups (hDPSCs alone group, NF-SMS alone group, and hDPSCs/NF-SMS group pre-cultured under normoxic conditions). Furthermore, in an in situ dental pulp repair model in rats, hypoxia-primed hDPSCs/NF-SMS were injected to fully fill the pulp cavity and regenerate pulp-like tissues with a rich vasculature and a histological structure similar to the native pulp. STATEMENT OF SIGNIFICANCE: Vascularization is key to the regeneration of many vital tissues. However, it is challenging to create a suitable microenvironment for stem cells to regenerate vascularized tissue structure. This manuscript reports a novel star-shaped block copolymer that self-assembles into unique nanofibrous spongy microspheres, which as an injectable scaffold recapitulate the cell-cell and cell-matrix interactions in development. Using a clinically-relevant surgical procedure and a hypoxic treatment, the nanofibrous spongy microspheres were used to deliver stem cells and successfully regenerate dental pulp with a rich vasculature and a complex histologic structure similar to that of the native dental pulp. The novel microspheres can likely be used to regenerate many other vascularized tissues. PMID- 26826530 TI - Zwitterionic fibrous polypropylene assembled with amphiphatic carboxybetaine copolymers for hemocompatible blood filtration. AB - The present study serves three main functions. First, it presents a novel random copolymer, made of octadecyl acrylate hydrophobic blocks and 2 (dimethylamino)ethyl methacrylate hydrophilic groups, and it zwitterionic form. Second, random copolymer and zwitterionic random copolymer, OmDn and Z-OmDn, are used to modify polypropylene membranes by evaporation coating. Our investigations unveil that this method leads to sufficiently stable self-assembling provided a minimum number of hydrophobic repeat units of 77, which also corresponds to a hydrophobic degree of 74%. Third, antifouling and hemocompatible properties of membranes are thoroughly investigated using all types of blood cells separately, as well as challenging membranes against whole blood in static and dynamic conditions. Membranes modified with zwitterionic copolymer containing 26% of zwitterionic groups are shown to be highly antifouling and hemocompatible, for a coating density as low as 0.2mg/cm(2). Their application in a specially designed blood filtration module enabled to almost totally inhibit blood cells interactions with membrane material, as well as to importantly reduce platelet activation in the permeate (2.5-fold reduction). STATEMENT OF SIGNIFICANCE: The design of new zwitterionic copolymer material is proposed and demonstrated in this study. It was showed that hydrophobicoctadecyl acrylate segments can be introduced in the zwitterioniccarboxybetaine polymer chain with a well-controlled random sequence. Stable, efficient, and effective surface zwitterionization of hydrophobic polypropylene are obtained via grafting onto approach by evaporation induced self-assembling coating. In the perspective of potential application, hemocompatible blood filtration was demonstrated with the excellent results of non-activated platelets obtained. SUMMARY OF IMPACTS: DESIGN: New zwitterionicmaterial, amphiphatic carboxybetaine copolymers. DEVELOPMENT: Evaporation-induced self-assembling grafting. APPLICATION: Hemocompatible blood filtration. PMID- 26826531 TI - Self-assembled gemcitabine-gadolinium nanoparticles for magnetic resonance imaging and cancer therapy. AB - Nanoparticles with combined diagnostic and therapeutic functions are promising tools for cancer diagnosis and treatment. Here, we demonstrate a theranostic nanoparticle that integrates an active gemcitabine metabolite and a gadolinium based magnetic resonance imaging agent via a facile supramolecular self-assembly synthesis, where the anti-cancer drug gemcitabine-5'-monophosphate (a phosphorylated active metabolite of the anti-cancer drug gemcitabine) was used to coordinate with Gd(III) to self-assemble into theranostic nanoparticles. The formulation exhibits a strong T1 contrast signal for magnetic resonance imaging of tumors in vivo, with enhanced retention time. Furthermore, the nanoparticles did not require other inert nanocarriers or excipients and thus had an exceptionally high drug loading (55 wt%), resulting in the inhibition of MDA-MB 231 tumor growth in mice. STATEMENT OF SIGNIFICANCE: Recent advances in nanoparticle-based drug delivery systems have spurred the development of "theranostic" multifunctional nanoparticles, which combine therapeutic and diagnostic functionalities in a single formulation. Developing simple and efficient synthetic strategies for the construction of nanotheranostics with high drug loading remains a challenge. Here, we demonstrate a theranostic nanoparticle that integrates high loadings of an active gemcitabine metabolite and a gadolinium-based magnetic resonance imaging agent via a facile synthesis. The nanoparticles were better T1 contrast agents than currently used Gd-DTPA and had prolonged retention in tumor. Moreover they exhibited enhanced in vivo antitumor activity compared to free drug in a breast cancer xenograft mouse model. The strategy provides a scalable way to fabricate nanoparticles that enables enhancement of both therapeutic and diagnostic capabilities. PMID- 26826532 TI - Differentiation of mesenchymal stem cells for cartilage tissue engineering: Individual and synergetic effects of three-dimensional environment and mechanical loading. AB - Chondrogenesis of dedifferentiated chondrocytes and mesenchymal stem cells is influenced not only by soluble molecules like growth factors, but also by the cell environment itself. The latter is achieved through both mechanical cues - which act as stimulation factor and influences nutrient transport - and adhesion to extracellular matrix cues - which determine cell shape. Although the effects of soluble molecules and cell environment have been intensively addressed, few observations and conclusions about the interaction between the two have been achieved. In this work, we review the state of the art on the single effects between mechanical and biochemical cues, as well as on the combination of the two. Furthermore, we provide a discussion on the techniques currently used to determine the mechanical properties of materials and tissues generated in vitro, their limitations and the future research needs to properly address the identified problems. STATEMENT OF SIGNIFICANCE: The importance of biomechanical cues in chondrogenesis is well known. This paper reviews the existing literature on the effect of mechanical stimulation on chondrogenic differentiation of mesenchymal stem cells in order to regenerate hyaline cartilage. Contradictory results found with respect to the effect of different modes of external loading can be explained by the different properties of the scaffolding system that holds the cells, which determine cell adhesion and morphology and spatial distribution of cells, as well as the stress transmission to the cells. Thus, this review seeks to provide an insight into the interplay between external loading program and scaffold properties during chondrogenic differentiation. The review of the literature reveals an important gap in the knowledge in this field and encourages new experimental studies. The main issue is that in each of the few cases in which the interplay is investigated, just two groups of scaffolds are compared, leaving intermediate adhesion conditions out of study. The authors propose broader studies implementing new high-throughput techniques for mechanical characterization of tissue engineering constructs and the inclusion of fatigue analysis as support methodology to more exhaustive mechanical characterization. PMID- 26826533 TI - Changes in the regional cerebral blood flow detected by arterial spin labeling after 6-week escitalopram treatment for major depressive disorder. AB - BACKGROUND: A few studies have used pseudo-continuous arterial spin labeling (pCASL) to assess the regional cerebral blood flow (rCBF) in patients with major depressive disorder (MDD). However, rCBF changes during treatment with escitalopram have not been studied in detail. We used pCASL to investigate the effect of 6-week escitalopram treatment on the rCBF in MDD patients. METHODS: We subjected 53 MDD patients and 36 controls to pCASL (T1, baseline). The patients then received treatment with escitalopram for 6 weeks and 27 were scanned again (T2). We used selected regions of interest that exhibited differences between the controls and patients at T1 and compared the T2 rCBF in the patients with the T1 rCBF of the controls. We also compared the T1 and T2 rCBF in the patients to assess their response to escitalopram. RESULTS: After 6-week treatment with escitalopram, the rCBF in the patients' left inferior temporal gyri, the middle- and inferior frontal gyri, and the subgenual anterior cingulate, which had been higher at T1 than in the controls, was decreased. Their rCBF in the right lingual gyrus remained significantly lower at T2. LIMITATION: We did not have a placebo control group and the number of patients available at T2 was small. CONCLUSION: In MDD patients, 6-week escitalopram treatment elicited significant rCBF changes toward normalization in most of the areas that had shown significant differences between the patients and the controls at T1. The persistence of rCBF anomalies in the right lingual gyrus may be a trait marker of MDD. PMID- 26826534 TI - Combining pharmacotherapy and psychotherapy or monotherapy for major depression? A meta-analysis on the long-term effects. AB - BACKGROUND: The present meta-analysis aimed to examine to what extent combined pharmacotherapy with psychotherapy results in a different response to treatment compared to psychotherapy or pharmacotherapy alone in adults with major depression at six months or longer postrandomization. METHODS: A systematic literature search resulted in 23 randomized controlled trials with 2184 participants. Combined treatment was compared to either psychotherapy or anti depressant medication alone in both the acute phase and the maintenance phase. Odds ratios of a positive outcome were calculated for all comparisons. RESULTS: In acute phase treatment, combined psychotherapy with antidepressants outperformed antidepressants alone at six months or longer postrandomization in patients with major depressive disorder (OR=2.93, 95%CI 2.15-3.99, p<0.001). Heterogeneity was zero (95%CI 0-57%, p>0.05). However, combined therapy resulted in equal response to treatment compared to psychotherapy alone at six months or longer postrandomization. As for the maintenance treatment, combined maintenance psychotherapy with antidepressants resulted in better-sustained treatment response compared to antidepressants at six months or longer postrandomization (OR=1.61, 95%CI 1.14-2.27, p<0.05). Heterogeneity was zero (95%CI 0-68%, p>0.05). CONCLUSIONS: Combined therapy results in a superior enduring effect compared to antidepressants alone in patients with major depression. Psychotherapy is an adequate alternative for combined treatment in the acute phase as it is as effective as combined treatment in the long-term. PMID- 26826535 TI - Abnormal functional connectivity density in first-episode, drug-naive adult patients with major depressive disorder. AB - Previous studies have found evidence of brain functional connectivity (FC) changes with pre-selected region-of-interest (ROI) method in major depressive disorder (MDD). However, these studies could not completely exclude personal inequality when drawing ROIs manually and did not measure the total number of FC for each voxel. Here, we firstly applied functional connectivity density (FCD) mapping, a voxel-based analysis to locate the hubs with amount changes of FC between 22 first-episode, drug-naive adult MDD patients and 22 healthy control (HC) subjects. Both short-range (local) FCD and long-range (distal) FCD were measured. The relationships of FCD changes with Hamilton Depression Rating Scale (HAMD) scores and illness duration were also explored. Compared with the HC group, MDD patients showed significantly decreased short-range FCD in the left superior temporal gyrus (STG), the right orbital frontal cortex (OFC) and bilateral precuneus, while significantly decreased long-range FCD was found in bilateral middle occipital gyrus (MOG), superior occipital gyrus (SOG) and right calcarine. These results firstly demonstrated both local and distal alterations of connection amount at voxel level, and highlighted that the OFC, the precuneus, the STG and the visual cortex were important brain network hubs for first episode, drug-naive adult MDD patients. Our findings were complementary for previous structural and functional studies in MDD patients, and provided new evidence of the dysfunction of connection hubs in the pathophysiology of MDD at voxel level. PMID- 26826536 TI - [Cardiovascular risk study in patients with renin-angiotensin system blockade by means of the proteone of circulating extracellular vesicles]. AB - INTRODUCTION: Extracellular vesicles (EVs) are released to the bloodstream by certain cell types due to transport, activation and cell death processes. Blood count of EVs from platelet and endothelial origin has been proved to be a cardiovascular risk biomarker. Thus, EVs proteome might reflect the underlying cellular processes in hypertensive patients with albuminuria. MATERIAL AND METHODS: Protein content of circulating EVs was analyzed by liquid chromatography coupled to mass spectrometry. EVs were isolated by an ultracentrifugation protocol optimized in order to avoid contamination by blood plasma proteins. Purity of the isolated fraction was verified by electronic and confocal microscopy, and by flow cytometry. RESULTS: We hereby show a method to isolate circulating EVs from hypertensive patients with/without albuminuria with high yield and purity. Besides, we provide a reference proteome of the EVs of these patients, composed of 2,463 proteins, and prove that the proteins carried by these vesicles are associated with crucial processes involved in the inherent cardiovascular risk. CONCLUSION: The proteome of circulating EVs is an interesting source of indicators in the evaluation of cardiovascular risk in hypertensive patients with renin-angiotensin system blockage. PMID- 26826537 TI - Functional Outcome of the Facial Nerve After Surgery for Vestibular Schwannoma: Prediction of Acceptable Long-Term Facial Nerve Function Based on Immediate Postoperative Facial Palsy. AB - OBJECTIVE: To examine the relationship between immediate postoperative facial palsy and long-term facial palsy and identify a treatment strategy for vestibular schwannoma considering long-term outcomes of facial nerve function and tumor control. METHODS: Patients (N = 385) who underwent surgery in a single institution were reviewed retrospectively; 12 patients with neurofibromatosis, 6 with preoperative radiosurgery, and 14 with multiple surgeries were excluded. The generalized estimating equation method was used to show the correlation between immediate and later postoperative facial palsy and to identify the cutoff grade of immediate postoperative facial palsy. RESULTS: The tumor control rates for 1 year, 3 years, and 5 years were 88.7%, 83.9%, and 80.0%. Preservation of facial function above House-Brackmann (H-B) grades 1 and 2 was achieved in 47.9% of patients immediately postoperatively, in 50.1% after 1 month, and in 74.5% after >2 years. The immediate postoperative facial palsy grade showed a statistically significant relationship with the facial palsy grade on long-term follow-up (P < 0.001). H-B grade 3 immediate postoperative facial palsy was identified as the cutoff grade that showed the most significant relationship between the grade of immediate postoperative facial palsy and the grades above the cutoff (H-B grade 1 3) on long-term follow-up (P < 0.001). CONCLUSIONS: H-B grade of immediate postoperative facial palsy can predict facial palsy at long-term follow-up. H-B grade 3 immediate postoperative facial palsy is the lowest tolerable grade that guarantees functional improvement on long-term follow-up. Planned facial nerve preservation surgery followed by radiosurgery is thought to be optimal treatment in patients with vestibular schwannoma for both tumor control and facial nerve function. PMID- 26826538 TI - Hemifacial Spasm Associated with Contralateral Foramen Magnum Meningioma. AB - BACKGROUND: Hemifacial spasm (HFS) caused by a contralateral tumor is extremely rare, and all previously reported cases involved tumors at the cerebellopontine angle. We provide the first report to our knowledge of HFS caused by a contralateral foramen magnum meningioma, which improved after tumor removal without microvascular decompression. CASE DESCRIPTION: An 80-year-old woman presented with HFS caused by a contralateral foramen magnum meningioma. She had a 3-year history of gradual worsening of right-sided HFS. Magnetic resonance imaging showed a homogeneous gadolinium-enhancing tumor occupying the left ventrolateral portion of the foramen magnum. The loop of the right anterior inferior cerebellar artery extended into the right pontomedullary junction, compressing the root exit zone (REZ) of the right facial nerve. After tumor removal, with no attempt of confirmation of vascular compression of the right facial nerve REZ, facial spasm gradually decreased and eventually almost disappeared. Postoperative magnetic resonance imaging revealed that the loop of anterior inferior cerebellar artery had shifted away from the right facial nerve REZ. Dorsal shift of the anterior inferior cerebellar artery loop toward the facial nerve REZ along with dorsal shift of the vertebral and basilar arteries secondary to the huge contralateral mass located in the ventrolateral portion of the foramen magnum was suggested to represent the main cause of facial spasm. CONCLUSIONS: Although an extremely rare condition, facial spasm can develop as a result of contralateral tumors in locations other than the cerebellopontine angle. PMID- 26826539 TI - Children's capacity to use cultural focal points in coordination problems. AB - Coordination problems require one to act based on expectations about how partners will act. In Experiment 1, 5-year-olds (n=57) had to hide a sticker in the box another child from their, or a different, culture was most likely to search in. Boxes were marked with cues presumed to be known by everybody, cultural members, or the child. Experiment 2 assessed 5-year-olds' (n=57) behavior in a competition scenario. In Experiment 1, children were more likely to hide in the cultural box when playing with a same- than a different-culture partner. In Experiment 2, children's behavior was the opposite. Thus by age 5, children are capable of modulating their actions in coordination problems, according to their partners' presumed knowledge. PMID- 26826540 TI - Inflammatory mechanisms contribute to microembolism-induced anxiety-like and depressive-like behaviors. AB - Poor vascular health, atherosclerosis, or cardiac procedures in the elderly result in clinically silent microvascular infarcts that increase susceptibility to larger ischemic episodes and can precipitate changes in mood and cognition. Although the mechanisms that underlie ischemia-induced behavioral changes have not been fully elucidated, chronic inflammation has been implicated in the pathogenesis. Independent of brain injury, elevated levels of inflammatory cytokines can lead to sickness behaviors and symptoms of depression. Furthermore, in the presence of brain injury, inflammatory activation may serve as the linchpin that precipitates dysregulation of biological systems leading to changes to behavior. In the current study, we tested the hypothesis that cerebral inflammation caused by diffuse ischemia is necessary for the expression of post injury anxiety- and depressive- like behavior. Using a microsphere embolism (ME) rodent model, we demonstrate prolonged elevations in expression of inflammatory genes in the hippocampus ipsilateral to the injury which are reflected in the contralateral hemisphere by two weeks following injury. Prophylactic administration of meloxicam, a preferential inhibitor of COX-2 activity, prevented both central inflammation and deficits in affective-like behaviors. Furthermore, meloxicam was more efficacious than the selective serotonin reuptake inhibitor fluoxetine in prevention of microembolism-induced changes in inflammation and behavior. These data demonstrate that inflammatory activation is necessary for microembolism-induced behavioral changes and suggest that anti inflammatory treatments may be an effective therapeutic strategy in patients with risk factors for vascular depression or prior to invasive cardiac procedures. PMID- 26826541 TI - Cadmium removal from urban stormwater runoff via bioretention technology and effluent risk assessment for discharge to surface water. AB - Bioretention technology, a low-impact development stormwater management measure, was evaluated for its ability to remove heavy metals (specifically cadmium, Cd) from urban stormwater runoff. Fine sand, zeolite, sand and quartz sand were selected as composite bioretention media. The effects of these materials on the removal efficiency, chemical forms, and accumulation and migration characteristics of Cd were examined in laboratory scale bioretention columns. Heretofore, few studies have examined the removal of Cd by bioretention. A five step sequential extraction method, a single-contamination index method, and an empirical migration equation were used in the experiments. The average Cd removal efficiency of quartz sand approached 99%, and removal by the other media all exceeded 90%. The media types markedly affected the forms of Cd found in the columns as well as its vertical migration rate. The Cd accumulated in the four media was mainly in residual form; moreover, accumulation of Cd occurred mainly in the surface layer of the bioretention column. The migration depth of Cd in the four media increased with elapsed time, in the following sequence: zeolite>quartz sand>fine sand>sand. In contrast, the migration rate decreased with elapsed time, and the migration rate of Cd was lowest in sand (0.015 m per annum over the first ten years). The comprehensive risk index analysis indicated that the risk arising from Cd discharge to surface water was "intermediate", and that the degree of risk was lowest in sand, then quartz sand, zeolite, and fine sand in sequence. These results indicate that the adsorption and accumulation of Cd in the four media are more significant than the migration of Cd. In addition, the results of Cd risk assessment for the effluent indicate that each of the four media can serve as long-term adsorption material in a bioretention facility for purifying stormwater runoff. PMID- 26826542 TI - Geographical disparities in prescription practices of lithium and clozapine: a community-based study. AB - OBJECTIVE: To explore the socioeconomic and health resource characteristics associated with geographical variations of lithium and clozapine dispensing rates in France. METHOD: The study was performed using reimbursement data from the French Insurance Healthcare system over the period 2006-2013 in a community-based sample of persons aged 16 years and over. An ecological design was used to assess whether lithium and clozapine prescribing rates were associated with socioeconomic and health resource characteristics of the zone of residence (n = 95 French administrative subdivisions). RESULTS: Large geographical disparities were observed in dispensing rates: lithium dispensing rates by zone of residence ranged from 0 to 6.6 per 1000 (mean 2.4 per 1000) and clozapine dispensing rates ranged from 0 to 4.9 per 1000 (mean 0.8 per 1000). Higher density of GPs and regular communication between mental health services and primary care were independently associated with higher rates of lithium and clozapine dispensing and with a higher proportion of lithium users among mood-stabilizer users. CONCLUSION: A sufficient density of GPs and an effective communication and collaboration between mental healthcare services and primary care seems to favor greater access to psychotropic drugs with demonstrated efficacy but often viewed as 'risky' to prescribe. PMID- 26826543 TI - A case for preART-adjusted endpoints in HIV therapeutic vaccine trials. AB - BACKGROUND: In a randomized, double-blind, placebo-controlled phase 2 clinical trial of Vacc-4x, a peptide-based therapeutic HIV-1 p24(Gag) vaccine candidate, 135 HIV-infected participants (vaccine:placebo=92:43) received a series of six immunizations while on combination antiretroviral therapy (cART). At week 28, all participants underwent an analytical treatment interruption (ATI) for up to 24 weeks. preART VL appeared to be higher among Vacc-4x recipients. Based on a previous analysis, during ATI viral load (VL) appeared to be lower in Vacc-4x recipients, but no difference in CD4 level was observed between Vacc-4x and placebo groups. We propose fold-change-based endpoints and report comparative analyses accounting for imbalanced preART VL and missing data. METHODS: All analyses included per-protocol (PP) participants who received the full immunization and underwent ATI. Linear regression models were used to identify predictors of study endpoints and to estimate the vaccine effect based on fold changes in CD4 counts or VL over preART values at week 40 or at set-point (geometric mean over weeks 48 and 52 values). We adjusted for potential baseline factors and used a multiple imputation approach to account for missing endpoints due to cART resumption or dropout. P-values were adjusted for multiple comparisons using q-values. RESULTS: preART VL and CD4 count were significant predictors of study endpoints. The vaccine recipients had a higher fold change in week 40 CD4 counts (vaccine vs. placebo mean fold-change difference=0.08; p=0.02; q=0.03), a higher fold change in CD4 count set-point (0.06; p=0.06; q=0.07), a lower fold change in week 40 VL (-0.47; p=0.03; q=0.05), and a lower fold change in VL set-point (-0.50; p=0.02; q=0.03). CONCLUSIONS: These exploratory analyses consistently suggested that Vacc-4x provided positive effects on both CD4 counts and VL. Future HIV therapeutic vaccine studies may adopt similar preART-adjusted endpoints and missing data imputation methods in vaccine effect evaluations. PMID- 26826544 TI - Immunogenicity and safety of a multicomponent meningococcal serogroup B vaccine in healthy adolescents in Korea--A randomised trial. AB - BACKGROUND: Neisseria meningitidis serogroup B is a significant cause of septicaemia and meningitis worldwide. This phase 3 randomised, controlled study assessed the immunogenicity and safety of a multicomponent meningococcal serogroup B vaccine, 4CMenB, in healthy Korean adolescents. METHODS: 264 adolescents (11-17 years old) were randomised to receive two doses, one month apart, of 4CMenB or control vaccines [placebo followed by one dose of a quadrivalent meningococcal ACWY glycoconjugate vaccine (MenACWY-CRM)]. Immunogenicity was evaluated by serum bactericidal assay with human complement (hSBA) against three serogroup B test strains specific for individual vaccine antigens (fHbp, NadA or PorA P1.4), and by enzyme-linked immunosorbent assay (ELISA) against the NHBA antigen. Solicited reactions and adverse events (AEs) were assessed. RESULTS: One month post-second vaccination, 98%, 97%, and 97% of subjects in the 4CMenB group achieved hSBA titres >= 4 against the fHbp, NadA and PorA test strains, respectively, while percentages in the Control group were comparable to baseline (27%, 16%, and 17%, respectively). Geometric mean ELISA concentrations (GMCs) against NHBA increased 52-fold relative to baseline in the 4CMenB group, while there was no substantial increase in GMCs in the Control group (1.05-fold). Frequencies of solicited reactions after any vaccination were higher in the 4CMenB group than in the Control group, although most reactions were of short duration and mild to moderate intensity. There were no vaccine related serious AEs. CONCLUSIONS: Two doses of 4CMenB induced robust immune responses against the vaccine antigens and were well tolerated, with no safety concerns identified, in Korean adolescents (NCT01973218). PMID- 26826545 TI - Recombinant influenza virus expressing HIV-1 p24 capsid protein induces mucosal HIV-specific CD8 T-cell responses. AB - Influenza viruses are promising mucosal vaccine vectors for HIV but their use has been limited by difficulties in engineering the expression of large amounts of foreign protein. We developed recombinant influenza viruses incorporating the HIV 1 p24 gag capsid into the NS-segment of PR8 (H1N1) and X31 (H3N2) influenza viruses with the use of multiple 2A ribosomal skip sequences. Despite the insertion of a sizable HIV-1 gene into the influenza genome, recombinant viruses were readily rescued to high titers. Intracellular expression of p24 capsid was confirmed by in vitro infection assays. The recombinant influenza viruses were subsequently tested as mucosal vaccines in BALB/c mice. Recombinant viruses were attenuated and safe in immunized mice. Systemic and mucosal HIV-specific CD8 T cell responses were elicited in mice that were immunized via intranasal route with a prime-boost regimen. Isolated HIV-specific CD8 T-cells displayed polyfunctional cytokine and degranulation profiles. Mice boosted via intravaginal route induced recall responses from the distal lung mucosa and developed heightened HIV-specific CD8 T-cell responses in the vaginal mucosa. These findings demonstrate the potential utility of recombinant influenza viruses as vaccines for mucosal immunity against HIV-1 infection. PMID- 26826547 TI - Long-term immunogenicity and safety of inactivated Hantaan virus vaccine (HantavaxTM) in healthy adults. AB - BACKGROUND: Hemorrhagic fever with renal syndrome is a serious health problem in Eurasian countries, including Korea and China. This study evaluated the long-term immunogenicity and safety of formalin-inactivated Hantaan virus vaccine (HantavaxTM). METHODS: A phase III, multi-center clinical trial was undertaken to evaluate the immunogenicity and safety of HantavaxTM (three-dose schedule at 0, 1, and 13 months) among healthy adults. Immune response was assessed using the plaque reduction neutralizing antibody test (PRNT) and immunofluorescent antibody assay (IFA). Antibody levels were measured pre-vaccination and at 2, 13, 14, 25, 37, and 49 months after the initial vaccination. Systemic and local adverse events were assessed. RESULTS: A total of 226 healthy subjects aged 19-75 years were enrolled. Following two primary doses of HantavaxTM, the seroconversion rate was 90.14% by IFA, but it was only 23.24% by PRNT50. With booster administration, seropositive rates were 87.32% and 45.07% at one month post-vaccination according to IFA and PRNT50, respectively. In young adults (19-39 years), the seropositive rate according to PRNT50 reached about 60% after booster vaccination. The mean duration of seropositive response was 735 days for PRNT50 and 845 days for IFA. Solicited local and systemic adverse events occurred in 47.79% and 25.22% of study subjects, respectively, and most were grade 1. CONCLUSION: HantavaxTM showed a booster effect and immunogenicity lasting two years with a three-dose schedule. The neutralizing antibody response was quite poor with two primary doses, so an early booster vaccination at 2-6 months might be warranted to provide timely protection to high-risk subjects. PMID- 26826548 TI - Partially reduced graphene oxide as highly efficient DNA nanoprobe. AB - This work investigates the effect of reduction degree on graphene oxide (GO)-DNA interaction and the fluorescence quenching mechanism. Partial reduced graphene oxide (pRGO), which maintains well water-dispersibility, is synthesized using a mild reduction method by incubating GO suspension under alkaline condition at room temperature. The fluorescence quenching enhances with the restoration degree of sp(2) carbon bonds and follows the static quenching mechanism. The binding constant values imply that pRGO has much stronger affinity with ssDNA than GO. Utilizing this highly efficient nanoprobe, a universal sensing strategy is proposed for homogeneous detection of DNA. Compared with the reported GO-based DNA, this present strategy has obvious advantages such as requirement of low nanoprobe dosage, significantly reduced background, fast fluorescence quenching, and improved sensitivity. Even without any amplification process, the limit of detection can reach as low as 50 pM. PMID- 26826546 TI - Novel ISCOMs from Quillaja brasiliensis saponins induce mucosal and systemic antibody production, T-cell responses and improved antigen uptake. AB - In the last decades, significant efforts have been dedicated to the search for novel vaccine adjuvants. In this regard, saponins and its formulations as "immunostimulating complexes" (ISCOMs) have shown to be capable of stimulating potent humoral and cellular immune responses, enhanced cytokine production and activation of cytotoxic T cells. The immunological activity of ISCOMs formulated with a saponin fraction extracted from Quillaja brasiliensis (QB-90 fraction) as an alternative to classical ISCOMs based on Quil A((r)) (IQA) is presented here. The ISCOMs prepared with QB-90, named IQB-90, typically consist of 40-50 nm, spherical, cage-like particles, built up by QB-90, cholesterol, phospholipids and antigen (ovalbumin, OVA). These nanoparticles were efficiently uptaken in vitro by murine bone marrow-derived dendritic cells. Subcutaneously inoculated IQB-90 induced strong serum antibody responses encompassing specific IgG1 and IgG2a, robust DTH reactions, significant T cell proliferation and increases in Th1 (IFN gamma and IL-2) cytokine responses. Intranasally delivered IQB-90 elicited serum IgG and IgG1, and mucosal IgA responses at distal systemic sites (nasal passages, large intestine and vaginal lumen). These results indicate that IQB-90 is a promising alternative to classic ISCOMs as vaccine adjuvants, capable of enhancing humoral and cellular immunity to levels comparable to those induced by ISCOMs manufactured with Quillaja saponaria saponins. PMID- 26826549 TI - Development and validation of a CE-MS method for the targeted assessment of amino acids in urine. AB - A CE-ESI-MS method was developed and validated for the separation and quantitative analysis of amino acids (AA) in urine. Experimental parameters related to the CE-MS interface, BGE, and mass spectrometer (MS) settings were optimized providing a good separation of 27 AA, including the isomers L-leucine, L-isoleucine, and L-alloisoleucine, in less than 30 min. The sheath liquid was composed by 0.50% formic acid in 60% (v,v) methanol-water delivered at a flow rate of 5 MUL/min. The BGE consisted of 0.80 mol/L formic acid at pH 1.96 and 15% methanol. A pH stacking procedure was implemented to enhance sensitivity (a 12.5% NH4 OH solution was injected at 0.5 psi/9 s prior to samples injected at 0.6 psi/20 s). The proposed method was validated according to FDA and ICH protocols exhibiting acceptable parameters. Analytical curves presented coefficients of determination from 0.996 to 0.9997 (with large F statistics and low p-values). LODs and quantification ranged from 0.63 to 29 MUmol/L and from 1.9 to 86 MUmol/L, respectively. Practical repeatability was obtained for all AA with coefficients of variation better than 0.55% CV (migration time) and 1.7% CV (peak area ratios; methionine sulfone as internal standard). Recoveries of AA in spiked urine ranged from 92.0 to 123% with few exceptions. Moreover, a successful quantification of AA in pooled control and test urine samples, which compose a vesicoureteral reflux cohort, was achieved showing the potential applicability of the proposed method for targeted metabolomics studies using CE-ESI-MS with an Ion Trap as mass analyzer. PMID- 26826551 TI - New versatile approach for analysis of PEG content in conjugates and complexes with biomacromolecules based on FTIR spectroscopy. AB - Here we report a new approach based on FTIR-spectroscopy for determining the degree of PEGylation in biomolecules. We show that the PEG COC peak (at 1089 cm( 1)) is the main analytically valuable band in IR spectra of PEG-containing systems: it is narrow and highly intense, it is well distinguished from absorption bands of other principal functional groups of proteins and other biopolymers (carbonyl, amide, hydroxyl etc), and therefore is easily identified in the IR spectra. The proposed method is therefore "reagent-free" and allows for fast and accurate determination of the PEGylation degree of biomolecules as well as the structural characteristics of bioconjugates from a single FTIR spectrum. The measurement is not dependent on PEG polymerization degree or branching and can be applied in a wide pH range, making it a convenient replacement of laborious and unreliable methods. The developed approach was successfully used to study the range of PEG-containing covalent conjugates with chitosan and non covalent complexes with anionic liposomes. The composition of PEG-chitosan conjugates as well as their storage stability was determined by the method based on FTIR-spectroscopy. In the case of non-covalent complexes, not only PEG content, but also the binding constants of PEG-containing ligands to the liposome membrane were evaluated with this approach. The results obtained by the FTIR method were confirmed by DLS and zeta-potential experiments where the formation of electrostatic complex was monitored by the increase in the particle radius (from 80 nm to 105 nm) and zeta-potential neutralization (from -20 mV to -12 mV). Direct comparison of the results of FTIR approach with that of TNBS or OPA titration methods shows very good agreement between the measurements, with the FTIR method showing much lower deviation. PMID- 26826550 TI - Usage patterns of aromatherapy among the French general population: A descriptive study focusing on dermal exposure. AB - Although likely benefits of aromatherapy are well documented, little is known about essential oils consumption and exposure to molecules present in the oils. The aim of our study was to determine usage patterns of 12 types of essential oils among a quite large panel, sorted per sex and quintile of age from birth to 70. A survey was conducted in September 2014 among 1507 French individuals, selected to build a representative panel of the general population. The key point of our study, apart from the fact that it has never been done among general population, was the focus on dermal exposure. Information about types of essential oils used, skin areas exposed, frequencies and quantities were collected. Our work revealed that some sub-populations could be significantly exposed to molecules of toxicological concern, especially in terms of skin sensitization. This work is the first step to assess human exposure to these molecules, and will help safety authorities and risk managers to protect the population. PMID- 26826552 TI - Smad3 deficiency inhibits dentate gyrus LTP by enhancing GABAA neurotransmission. AB - Transforming growth factor-beta signaling through intracellular Smad3 has been implicated in Parkinson's disease (PD) and it fulfills an important role in the neurogenesis and synaptic plasticity that occurs in the adult dentate gyrus (DG). The long-term potentiation (LTP) induced in the DG by high-frequency stimulation of the medial perforant pathway is abolished in the DG of Smad3-deficient mice, but not in the CA1 hippocampal region. Here, we show that NMDA- and AMPA-type glutamate receptors do not participate in the inhibition of LTP associated with Smad3 deficiency. Moreover, there is no difference in the hippocampal GAD65 and GAD67 content, suggesting that GABA biosynthesis remains unaffected. Increased conductance and higher action potential firing thresholds were evident in intracellular recordings of granule cells from Smad3 deficient mice. Interestingly, phasic and tonic GABAA receptor (GABAA R)-mediated neurotransmission is enhanced in the DG of Smad3-deficient mice, and LTP induction can be rescued by inhibiting GABAA R with picrotoxin. Hence, Smad3 signaling in the DG appears to be necessary to induce LTP by regulating GABAA neurotransmission, suggesting a central role of this intracellular signaling pathway in the hippocampal brain plasticity related to learning and memory. Smad3 deficient mice represent a new and interesting model of Parkinson's disease, displaying hippocampal dysfunctions that include decreased neurogenesis and the failure to induce LTP in the dentate gyrus. Here we show that Smad3 deficiency inhibits LTP induction by enhancing phasic and tonic GABAA receptor-mediated neurotransmission, while LTP induction can be rescued with a GABAA receptor antagonist. Alteration of GABA neurotransmission is thought to produce hippocampal cognitive dysfunction in Down's syndrome or Alzheimer's disease, and here we provide new insights into the hippocampal changes in an animal model of Parkinson's disease. PMID- 26826553 TI - miR-144-3p, a tumor suppressive microRNA targeting ETS-1 in laryngeal squamous cell carcinoma. AB - Regional lymph node metastasis and distant metastasis are critical in the prognosis of laryngeal squamous cell carcinoma (LSCC). This study investigated the roles of miR-144-3p and E26 transformation specific-1 (ETS-1) in the invasion and migration of LSCC cells. The effects of miR-144-3p and ETS-1 on FaDu and Hep2 cell growth, migration and invasion were determined. Suppression of ETS-1 by miR 144-3p was confirmed using luciferase assays; the effects of ETS-1 silencing were determined using a xenograft tumor model. The expression of ETS-1 was analyzed in 71 paraffin-embedded tissue biopsies and eight fresh frozen biopsies obtained from LSCC patients. miR-144-3p inhibited the growth, invasion and migration of FaDu and Hep2 cells in part through suppression of epithelial-mesenchymal transition as determined by increased E-cadherin and alpha-catenin and reduced fibronectin and vimentin expression. Additionally, ETS-1 is a molecular target of miR-144-3p, and silencing ETS-1 expression inhibited FaDu and Hep2 cell invasion and migration as well as reduced Hep2 xenograft tumor volume. In LSCC, the expression of ETS-1 is upregulated with disease progression, and higher ETS-1 expression, which was negatively associated with miR-144-3p levels, adversely corresponded with prognoses. Thus, upregulated ETS-1 levels may promote LSCC metastasis, resulting in poor patient prognosis. PMID- 26826554 TI - Frequency and mitotic heritability of epimutations in Schistosoma mansoni. AB - Schistosoma mansoni is a parasitic platyhelminth responsible for intestinal bilharzia. It has a complex life cycle, infecting a freshwater snail of the Biomphalaria genus, and then a mammalian host. Schistosoma mansoni adapts rapidly to new (allopatric) strains of its intermediate host. To study the importance of epimutations in this process, we infected sympatric and allopatric mollusc strains with parasite clones. ChIP-Seq was carried out on four histone modifications (H3K4me3, H3K27me3, H3K27ac and H4K20me1) in parallel with genomewide DNA resequencing (i) on parasite larvae shed by the infected snails and (ii) on adult worms that had developed from the larvae. No change in single nucleotide polymorphisms and no mobilization of transposable elements were observed, but 58-105 copy number variations (CNVs) within the parasite clones in different molluscs were detected. We also observed that the allopatric environment induces three types of chromatin structure changes: (i) host-induced changes on larvae epigenomes in 51 regions of the genome that are independent of the parasites' genetic background, (ii) spontaneous changes (not related to experimental condition or genotype of the parasite) at 64 locations and (iii) 64 chromatin structure differences dependent on the parasite genotype. Up to 45% of the spontaneous, but none of the host-induced chromatin structure changes were transmitted to adults. In our model, the environment induces epigenetic changes at specific loci but only spontaneous epimutations are mitotically heritable and have therefore the potential to contribute to transgenerational inheritance. We also show that CNVs are the only source of genetic variation and occur at the same order of magnitude as epimutations. PMID- 26826555 TI - Aspirin treatment exacerbates oral infections by Trypanosoma cruzi. AB - Oral transmission of the protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas disease, has been documented in Latin American countries. The reported cases of infection were due to the ingestion of contaminated fresh fruit, juices, or sugar cane juice. There have been few studies on the physiopathology of the disease in oral transmission cases. Gastritis is a common ailment that can be caused by poor dietary habits, intake of alcohol or other gastric irritants, bacterial infection, or by the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs). This study investigated in a mouse model whether gastric mucosal injury, induced by aspirin, would affect the course of disease in animals infected with T. cruzi by the oral route. The CL14 and G strains of T. cruzi, both of low infectivity, were used. To this end, groups of BALB/c mice were treated during 5 days with aspirin (100 mg kg(-1)) before oral infection with T. cruzi metacyclic forms (4 * 10(5) or 5 * 10(7) parasites/mouse). Histological analysis and determination of nitric oxide and TNF alpha were performed in gastric samples obtained 5 days after infection. Parasitemia was monitored from the thirteenth day after infection. The results indicate that aspirin treatment of mice injured their gastric mucosa and facilitated invasion by both CL14 and G strains of T. cruzi. Strain CL14 caused more severe infection compared to the G strain, as larger numbers of amastigote nests were found in the stomach and parasitemia levels were higher. Our study is novel in that it shows that gastric mucosal damage caused by aspirin, a commonly used NSAID, facilitates T. cruzi infection by the oral route. PMID- 26826556 TI - Mismatch repair deficiency in Lynch syndrome-associated colorectal adenomas is more prevalent in older patients. AB - AIMS: The aim of this study was to examine the expression of mismatch repair (MMR) proteins in Lynch syndrome (LS)-associated colorectal adenomas and to evaluate their relationship with clinicopathological variables and potential utility in LS screening. METHODS AND RESULTS: We performed immunohistochemistry for MLH1, PMS2, MSH2 and MSH6 in 134 adenomas obtained from 26 genetically confirmed LS patients. MMR deficiency, as determined by loss of any MMR protein, was observed in 113 adenomas (84%). All the MMR-deficient adenomas exhibited homogeneous loss of MMR proteins, which reflected underlying germline mutations. MMR deficiency was more frequent in adenomas obtained from older patients (aged >=60 years; 81 of 86, 94%), with larger tumour size (>5 mm; 71 of 73, 97%) and with high-grade dysplasia (50 of 51, 98%). Multivariate analyses indicated that increased age and larger tumour size were associated independently with MMR deficiency. CONCLUSIONS: This study shows that MMR deficiency is associated significantly with increased age, in addition to two previously reported factors larger size and high-grade dysplasia. When adenomas are analysed during LS screening, high sensitivity is expected if the adenomas are associated with any of these three factors. PMID- 26826557 TI - Insight into the possible mechanism of the summer diapause of Delia antiqua (Diptera: Anthomyiidae) through digital gene expression analysis. AB - The onion fly, Delia antiqua, is a major underground agricultural pest that can enter pupal diapause in the summer and winter seasons. However, little is known about its molecular regulation due to the lack of genomic resources. To gain insight into the possible mechanism of summer diapause (SD), high-throughput RNA Seq data were generated from non-diapause (ND) and SD (initial, maintenance and quiescence phase) pupae. Three pair-wise comparisons were performed and identified, 1380, 1471 and 435, and were significantly regulated transcripts. Further analysis revealed that the enrichment of several functional terms related to juvenile hormone regulation, cell cycle, carbon hydrate and lipid metabolism, innate immune and stress responses, various signalling transductions, ubiquitin dependent proteosome, and variation in cuticular and cytoskeleton components were found between ND and SD and between different phases of SD. Global characterization of transcriptome profiling between SD and ND contributes to the in-depth elucidation of the molecular mechanism of SD. Our results also offer insights into the evolution of insect diapause and support the importance of using the onion fly as a model to compare the molecular regulation events of summer and winter diapauses. PMID- 26826558 TI - Nanotechnology-based strategies for combating toxicity and resistance in melanoma therapy. AB - Drug toxicity and resistance remain formidable challenges in cancer treatment and represent an area of increasing attention in the case of melanoma. Nanotechnology represents a paradigm-shifting field with the potential to mitigate drug resistance while improving drug delivery and minimizing toxicity. Recent clinical and pre-clinical studies have demonstrated how a diverse array of nanoparticles may be harnessed to circumvent known mechanisms of drug resistance in melanoma to improve therapeutic efficacy. In this review, we discuss known mechanisms of resistance to various melanoma therapies and possible nanotechnology-based strategies that could be used to overcome these barriers and improve the pharmacologic arsenal available to combat advanced stage melanoma. PMID- 26826559 TI - Cholesterol-independent effects of atorvastatin prevent cardiovascular morbidity and mortality in a mouse model of atherosclerotic plaque rupture. AB - Because cholesterol-independent effects of statins are difficult to determine in patients, we studied these pleiotropic effects in apolipoprotein E-deficient (ApoE(-/-)) mice with a mutation in the fibrillin-1 gene (Fbn1(C1039G+/-)). These mice develop exacerbated atherosclerosis and spontaneous plaque ruptures, accompanied by myocardial infarctions (MI) and sudden death. ApoE(-/ )Fbn1(C1039G+/-) mice were fed a Western diet (WD). At week 10 of WD, mice were divided in a control (WD), atorvastatin (10mg/kg/day + WD) and cholesterol withdrawal group (cholW, normal chow). The latter was included to compare the effects of atorvastatin with dietary lipid lowering. Fifteen weeks later, the mice were sacrificed. CholW, but not atorvastatin, reduced plasma cholesterol. Survival increased from 50% to 90% both in cholW and atorvastatin treated mice. CholW as well as atorvastatin treatment increased plaque collagen and fibrous cap thickness, but they did not affect the amount of plaque macrophages and T cells. MMP-2 and MMP-9 activity was significantly lower and the expression of MMP-12, TNF-alpha and IL-1beta was strongly reduced in both treatment groups. Blood monocytes and neutrophils returned to baseline levels (ApoE(-/-) mice before the onset of atherosclerosis). Importantly, atorvastatin but not cholW significantly reduced coronary stenosis (from 50 to 28%) and the occurrence of MI (from 43 to 10%). In conclusion, independent of cholesterol lowering, atorvastatin significantly reduced mortality, plaque vulnerability and inflammation to the same extent as cholW. In addition, atorvastatin but not cholW reduced coronary stenosis and the occurrence of MI. These data unequivocally illustrate the significance of the pleiotropic effects of atorvastatin in the prevention of cardiovascular morbidity and mortality. PMID- 26826560 TI - Resting cysts of Parentocirrus hortualis Vobeta, 1997 (Ciliophora, Hypotrichia), with preliminary notes on encystation and various types of excystation. AB - Resting cysts of Parentocirrus hortualis were investigated, using live observation, SEM and TEM. Processes during encystation and excystation were observed in vivo under the light microscope. During encystation, the trophic body becomes globular, the ciliature is resorbed in an anterior direction, the macronuclear nodules fuse into an elongated mass, and finally a cyst wall develops. As typical for oxytrichids, the resting cysts of P. hortualis are of the kinetosome-resorbing type and their wall is made of four layers: ectocyst, mesocyst, endocyst, and metacyst. The beginning of excystation is indicated by the formation of an excystation vacuole that helps the regenerating specimen to break the cyst wall. The excysting specimen leaves the resting cyst in a thin membrane that is gradually resorbed in the outer environment. Also two other excystation modes were observed. During the rare mode, the excystation vacuole breaks the thin membrane instead of the cyst wall that ruptures under the pressure of the body of the regenerating specimen. During the reproduction mode, the regenerating specimen divides within the resting cyst, producing two to four tomites. This is the first report of division in resting cysts of oxytrichids, but reproduction in division cysts was already described in keronopsids. PMID- 26826561 TI - Inflammatory markers following resuscitation from out-of-hospital cardiac arrest A prospective multicenter observational study. AB - AIM: The post-cardiac arrest syndrome is a complex set of pathophysiological processes including a systemic inflammatory response. The goal of the current investigation was to test the hypothesis that early inflammatory markers are independently associated with in-hospital mortality and poor neurological outcome in patients initially resuscitated from out-of-hospital cardiac arrest. METHODS: This was a preplanned analysis of data collected from a prospective observational multicenter study in adult out-of-hospital cardiac arrest patients. Blood was drawn at baseline, 12 and 24h after return of spontaneous circulation and plasma levels of interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-alpha were measured. The primary outcome measure was survival to hospital discharge. We utilized a mixed linear model to compare the levels of cytokines in survivors and non-survivors over time. We used multivariable logistic regression to assess the association between IL-6 levels and mortality. RESULTS: A total of 102 patients were analyzed. Non-survivors and patients with poor functional outcome had statistical significant higher IL-1Ra, IL-6, IL-8, and IL-10 levels (all p<0.001) at all time points (0, 12 and 24h) compared to survivors. Baseline IL-6 levels were a good predictor of mortality (AUC=0.83 [95%CI: 0.75-0.92]). Baseline IL-6 levels were strongly associated with mortality in multivariable analysis (OR: 2.58 [95%CI: 1.93-3.45], p<0.001) but were not associated with neurological outcome in multivariable analysis (OR: 1.33 [95%CI: 0.62-2.86], p=0.47). CONCLUSION: Early inflammatory markers, especially IL-6, are higher in patients with a poor outcome after OHCA. IL-6 remained associated with mortality, but not functional outcome, in multivariable analysis adjusting for patient and event characteristics. PMID- 26826562 TI - Plasma neutrophil gelatinase-associated lipocalin as an early predicting biomarker of acute kidney injury and clinical outcomes after recovery of spontaneous circulation in out-of-hospital cardiac arrest patients. AB - AIMS: To determine whether the level of plasma neutrophil gelatinase-associated lipocalin (NGAL) can predict acute kidney injury (AKI) and clinical outcomes after recovery of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA). METHODS: We conducted a prospective observational study of consecutive admitted patients with ROSC after OHCA between January 2013 and March 2015. Plasma was collected within 4h of ROSC to determine the level of NGAL. Outcome variables were AKI, 30-day survival, and good neurological outcome (GNO). We evaluated the association between NGAL and outcomes. RESULTS: Fifty-four patients were included. AKI occurred in 26 (48.0%); 15 (27.7%) survived over 30 days and 8 had GNO (14.8%). NGAL was significantly lower in the group with non AKI, 30-day survival, and GNO. To predict AKI, 30-day survival, and GNO, the area under the receiver operating characteristic curve for NGAL was 0.810, 0.728, and 0.875, respectively. In a logistic regression model, NGAL >189 ngml(-1) was strongly associated with AKI (odds ratio [OR] 7.01, 95% confidence interval [CI]: 1.89-26.01) in a multivariate model. A lower level of NGAL was strongly associated with 30-day survival (OR 6.12, 95% CI: 1.64-23.42 at NGAL <153.5 ngml( 1)) and GNO (OR 19.83, 95% CI: 2.21-178.32 at NGAL <129.5 ngml(-1)) in a univariate model, but was not significantly associated with outcomes in a multivariate model. CONCLUSIONS: Plasma NGAL is a strong predictor of AKI in patients exhibiting OHCA at ICU admission. Lower levels of NGAL are associated with greater chance of 30-day survival and GNO. PMID- 26826563 TI - Long-term neurologic outcomes following paediatric out-of-hospital cardiac arrest. AB - AIM: Evaluate long-term neurologic outcome for paediatric survivors of OHCA. METHODS: Subjects <19 years who experienced OHCA from 1976-2007 and survived to hospital discharge were included. Demographics, neurologic outcomes and years of survival were determined using the King County Emergency Medical Service cardiac arrest database, Seattle Children's Hospital medical records, Washington State Death Database and National Death Index. A Paediatric Cerebral Performance Category (PCPC) score (1-6) was determined for the index hospitalization discharge and all subsequent visits. RESULTS: From 1976-2007, 1683 cases of OHCA resulted in 91 survivors to hospital discharge. 18/91 survivors identified had pre-morbid conditions. 72/91 survivors had follow-up PCPC scores. Patients were: <=5 years (53%) and 54% female. 33/35 patients with initial favorable neurologic outcomes (PCPC 1-2) maintained favorable neurologic status in long-term follow up. 14/37 patients with initial unfavorable neurologic outcomes (PCPC 3-5) remained unfavorable over long-term follow-up. Six unfavorable patients showed some improvement, three of whom achieved favorable PCPC scores at last evaluation. One unfavorable patient declined from PCPC 4 to PCPC 5. Twenty patients with an initial unfavorable neurologic outcome died in long-term follow up. CONCLUSIONS: In this cohort study of neurologic outcomes for paediatric OHCA survivors, a favorable initial PCPC score was highly associated with stable long term neurological outcomes. Those with poor neurologic status at initial discharge were unlikely to improve and were at greatest risk to die in follow-up. Future studies should focus on improving neurologic outcomes and prospectively evaluating the long-term neurologic course. PMID- 26826564 TI - Long-term neurological outcomes in patients after out-of-hospital cardiac arrest. AB - AIM: The main treatment goal in survivors of out-of-hospital cardiac arrest (OHCA) is a favorable neurologic outcome. Little is known, however, about long term trends of neurologic status in OHCA survivors. This study was designed to assess the rates of long-term neurologic recovery and survival according to neurologic status at one month. METHODS: This retrospective observational study assessed all adult OHCA survivors (>=18 years) admitted to a tertiary hospital in an urban area who achieved return of spontaneous circulation (ROSC) between July 2005 and August 2013. Neurologic outcomes were measured by Cerebral Performance Category (CPC) score and patients were categorized according to CPC score at 1 month. Their neurologic status was re-evaluated 6, 12, and 24 months after cardiac arrest. RESULTS: Of 778 OHCA cases, 282 patients (36.2%) were admitted to our hospital, and 279 were included in this study. At one month, 84 (30.1%) survivors were assessed with the CPC with 42.8% (n=36) having good neurologic outcome and 57.1% (n=48) poor neurologic outcome. Only two patients with poor neurologic outcome (4.1%) showed improved neurologic status from CPC 3 to CPC 2, during the first 6 months and none showed neurologic improvement after 6 months. The estimated 3-year survival was much higher for CPC 1 (96.4%) than for CPC 4 (24.2%) survivors. CONCLUSIONS: Neurologic recovery of OHCA survivors with poor neurologic outcomes at one month was rare and did not occur more than 6 months after cardiac arrest. PMID- 26826565 TI - Influence of mannan-binding lectin and MAp44 on outcome in comatose survivors of out-of-hospital cardiac arrest. AB - AIM: The lectin complement pathway, initiated by mannan-binding-lectin (MBL) plays a role in tissue destruction following ischemia/reperfusion, and MBL deficiency has been associated with favorable outcome in stroke patients. MAp44 is produced in the heart and may theoretically function as an endogenous inhibitor of MBL-mediated activities. The aim of this study was to investigate the possible association between MBL deficiency, MAp44 levels and outcome in comatose survivors of out-of-hospital cardiac arrest (OHCA). METHODS: In a single center post hoc analysis of the prospective multicenter randomized Target Temperature Management (TTM) trial, we measured MBL and MAp44 levels at baseline, 24, 48 and 72 h after OHCA in 169 consecutive patients randomly assigned to TTM at 33 degrees C or 36 degrees C for 24h. Primary outcome was 30 days mortality and secondary outcome was favorable neurological outcome assessed by Cerebral Performance Category (CPC1-2) and modified Rankin Scale (mRS0-3) 180 days after OHCA. RESULTS: Patients with MBL deficiency (defined as plasma levels <=100 ngml( 1) at baseline) (n=22) carried a 30-day mortality of 41% compared to 32% in MBL sufficient patient (n=147), p=0.55. Baseline MAp44 levels were not associated with mortality, p=0.25. There was no significant difference in neurological outcome between the two MBL groups assessed by CPC (p=0.69) and mRS (p=0.91). In multivariable models, baseline MBL (OR=1.0, p=0.70), (OR=1.5, p=0.30) and MAp44 levels (OR=1.0, p=0.99), (OR=1.6, p=0.21) were not associated with favorable neurological outcome assessed by CPC and mRS, respectively. CONCLUSIONS: In comatose survivors after cardiac arrest, neither MBL deficiency nor levels of MBL and MAp44 were associated with mortality or neurological outcome. PMID- 26826566 TI - Concerns about 2015 ERC Guidelines on pre-hospital use of ADP-receptor antagonists in patients with STEMI (ACS 335). PMID- 26826567 TI - The slow relaxation dynamics in active pharmaceutical ingredients studied by DSC and TSDC: Voriconazole, miconazole and itraconazole. AB - The slow molecular mobility of three active pharmaceutical drugs (voriconazole, miconazole and itraconazole) has been studied by differential scanning calorimetry (DSC) and thermally stimulated depolarization currents (TSDC). This study yielded the main kinetic features of the secondary relaxations and of the main (glass transition) relaxation, in particular their distribution of relaxation times. The dynamic fragility of the three glass formers was determined from DSC data (using two different procedures) and from TSDC data. According to our results voriconazole behaves as a relatively strong liquid, while miconazole is moderately fragile and itraconazole is a very fragile liquid. There are no studies in this area published in the literature relating to voriconazole. Also not available in the literature is a slow mobility study by dielectric relaxation spectroscopy in the amorphous miconazole. Apart from that, the results obtained are in reasonable agreement with published works using different experimental techniques. PMID- 26826568 TI - Oil-based compositions as saliva substitutes: A pilot study to investigate in mouth retention. AB - OBJECTIVES: This pilot study aimed to compare the in-mouth retention of an oil based saliva substitute (emulsion, consisting of rice bran oil, soy lecithin and water) with water and a 1% w/v methylcellulose suspension (polymer) in healthy volunteers. METHODS: Each formulation was tagged with 1 mmol/L lithium and participants (n=30) rinsed their mouth with one randomly assigned formulation (emulsion, polymer or water) for 30s, before expectorating into a cup. Concentration of lithium expectorated was measured and amount of each formulation remaining in the mouth was estimated. Patient acceptability was investigated using questionnaires, and Fourier-Transform Infrared spectroscopy (FTIR) was used to determine the presence of oil in expectorated samples. RESULTS: Immediately after rinsing, taste was rated lower in the emulsion group compared to the polymer or water groups (p>0.05), although variability was high. Mean retention was highest in the emulsion group, with a difference of 8.34 +/- 2.71% (p=0.003) and 4.57 +/- 2.71% (p=0.06) compared with the water and polymer groups, respectively. FTIR confirmed the presence of oil in all expectorated emulsion samples. CONCLUSION: The emulsion was not inferior to the polymer in terms of retention immediately after rinsing. The next step is to conduct larger clinical studies over longer time periods in participants with salivary hypofunction. PMID- 26826569 TI - Ex vivo permeation of carprofen from nanoparticles: A comprehensive study through human, porcine and bovine skin as anti-inflammatory agent. AB - The purpose of this study was the development of poly(d,l-lactide-co-glycolide) acid (PLGA) nanoparticles (NPs) for the dermal delivery of carprofen (CP). The developed nanovehicle was then lyophilized using hydroxypropyl-beta-cyclodextrin (HPbetaCD) as cryoprotectant. The ex vivo permeation profiles were evaluated using Franz diffusion cells using three different types of skin membranes: human, porcine and bovine. Furthermore, biomechanical properties of skin (trans epidermal water loss and skin hydration) were tested. Finally, the in vivo skin irritation and the anti-inflammatory efficacy were also assayed. Results demonstrated the achievement of NPs 187.32 nm sized with homogeneous distribution, negatively charged surface (-23.39 mV) and high CP entrapment efficiency (75.38%). Permeation studies showed similar diffusion values between human and porcine skins and higher for bovine. No signs of skin irritation were observed in rabbits. Topically applied NPs significantly decreased in vivo inflammation compared to the reference drug in a TPA-induced mouse ear edema model. Thus, it was concluded that NPs containing CP may be a useful tool for the dermal treatment of local inflammation. PMID- 26826571 TI - Infliximab Efficacy and Safety in an Ulcerative Colitis Patient with Systemic Lupus Erythematosus. PMID- 26826570 TI - Evidence for maternal control of seed size in maize from phenotypic and transcriptional analysis. AB - Seed size is an important component of grain yield and a key determinant trait for crop domestication. The Krug Yellow Dent long-term selection experiment for large and small seed provides a valuable resource to dissect genetic and phenotypic changes affecting seed size within a common genetic background. In this study, inbred lines derived from Krug Large Seed (KLS) and Krug Small Seed (KSS) populations and reciprocal F1 crosses were used to investigate developmental and molecular mechanisms governing seed size. Seed morphological characteristics showed striking differences between KLS and KSS inbred lines, and the reciprocal cross experiment revealed a strong maternal influence on both seed weight and seed size. Quantification of endosperm area, starchy endosperm cell size, and kernel dry mass accumulation indicated a positive correlation between seed size, endosperm cell number, and grain filling rate, and patterns of grain filling in reciprocal crosses mirrored that of the maternal parent. Consistent with the maternal contribution to seed weight, transcriptome profiling of reciprocal F1 hybrids showed substantial similarities to the maternal parent. A set of differentially expressed genes between KLS and KSS inbreds were found, which fell into a broad number of functional categories including DNA methylation, nucleosome assembly, and heat stress response. In addition, gene co expression network analysis of parental inbreds and reciprocal F1 hybrids identified co-expression modules enriched in ovule development and DNA methylation, implicating these two processes in seed size determination. These results expand our understanding of seed size regulation and help to uncover the developmental and molecular basis underlying maternal control of seed size in maize. PMID- 26826572 TI - Effects of light-emitting diodes under capped daily energy consumption with combinations of electric power and photoperiod on cultivation of Chlorella pyrenoidosa. AB - Effects of white light-emitting diodes (LEDs) with different light intensities at photoperiod of 18:6h on Chlorella pyrenoidosa growth were investigated. The microalgae exhibited the highest growth rate 89.0mgL(-1)d(-1) and growth efficiency 97.8mgL(-1)KWh(-1) at 110 and 90MUmolm(-2)s(-1), respectively. Based on the discovery of this asynchronous phenomenon between growth rate and growth efficiency, influences of LEDs (red, blue and white) under capped daily energy consumption (0.80KWh d(-1)) with combinations of electric power (33.3, 44.4 and 66.6w) and photoperiod (24:0, 18:6 and 12:12h) were further investigated. The highest growth efficiency 106.4mgL(-1)KWh(-1) and growth rate 85.1mgL(-1)d(-1) were both obtained under white-33.3w-24h. Growth efficiency and growth rate were simultaneously improved 1.1 times through this method above. The order of growth efficiency under different LEDs were white>blue>red. PMID- 26826573 TI - Thermodynamic analyses of a biomass-coal co-gasification power generation system. AB - A novel chemical looping power generation system is presented based on the biomass-coal co-gasification with steam. The effects of different key operation parameters including biomass mass fraction (Rb), steam to carbon mole ratio (Rsc), gasification temperature (Tg) and iron to fuel mole ratio (Rif) on the system performances like energy efficiency (etae), total energy efficiency (etate), exergy efficiency (etaex), total exergy efficiency (etatex) and carbon capture rate (etacc) are analyzed. A benchmark condition is set, under which etate, etatex and etacc are found to be 39.9%, 37.6% and 96.0%, respectively. Furthermore, detailed energy Sankey diagram and exergy Grassmann diagram are drawn for the entire system operating under the benchmark condition. The energy and exergy efficiencies of the units composing the system are also predicted. PMID- 26826574 TI - Effects of high fat diets on rodent liver bioenergetics and oxidative imbalance. AB - Human metabolic diseases can be mimicked in rodents by using dietary interventions such as high fat diets (HFD). Nonalcoholic fatty liver disease (NAFLD) develops as a result of HFD and the disease may progress in a manner involving increased production of oxidants. The main intracellular source of these oxidants are mitochondria, which are also responsible for lipid metabolism and thus widely recognized as important players in the pathology and progression of steatosis. Here, we review publications that study redox and bioenergetic effects of HFD in the liver. We find that dietary composition and protocol implementations vary widely, as do the results of these dietary interventions. Overall, all HFD promote steatosis, changes in beta-oxidation, generation and consequences of oxidants, while effects on body weight, insulin signaling and other bioenergetic parameters are more variable with the experimental models adopted. Our review provides a broad analysis of the bioenergetic and redox changes promoted by HFD as well as suggestions for changes and specifications in methodologies that may help explain apparent disparities in the current literature. PMID- 26826576 TI - KatB, a cyanobacterial Mn-catalase with unique active site configuration: Implications for enzyme function. AB - Manganese catalases (Mn-catalases), a class of H2O2 detoxifying proteins, are structurally and mechanistically distinct from the commonly occurring catalases, which contain heme. Active site of Mn-catalases can serve as template for the synthesis of catalase mimetics for therapeutic intervention in oxidative stress related disorders. However, unlike the heme catalases, structural aspects of Mn catalases remain inadequately explored. The genome of the ancient cyanobacterium Anabaena PCC7120, shows the presence of two Mn-catalases, KatA and KatB. Here, we report the biochemical and structural characterization of KatB. The KatB protein (with a C-terminal his-tag) was over-expressed in Escherichia coli and purified by affinity chromatography. On the addition of Mn(2+) to the E. coli growth medium, a substantial increase in production of the soluble KatB protein was observed. The purified KatB protein was an efficient catalase, which was relatively insensitive to inhibition by azide. Crystal structure of KatB showed a hexameric assembly with four-helix bundle fold, characteristic of the Ferritin like superfamily. With canonical Glu4His2 coordination geometry and two terminal water ligands, the KatB active site was distinctly different from that of other Mn-catalases. Interestingly, the KatB active site closely resembled the active sites of ruberythrin/bacterioferritin, bi-iron members of the Ferritin-like superfamily. The KatB crystal structure provided fundamental insights into the evolutionary relationship within the Ferritin-like superfamily and further showed that Mn-catalases can be sub-divided into two groups, each with a distinct active site configuration. PMID- 26826575 TI - Increasing tetrahydrobiopterin in cardiomyocytes adversely affects cardiac redox state and mitochondrial function independently of changes in NO production. AB - Tetrahydrobiopterin (BH4) represents a potential strategy for the treatment of cardiac remodeling, fibrosis and/or diastolic dysfunction. The effects of oral treatment with BH4 (SapropterinTM or KuvanTM) are however dose-limiting with high dose negating functional improvements. Cardiomyocyte-specific overexpression of GTP cyclohydrolase I (mGCH) increases BH4 several-fold in the heart. Using this model, we aimed to establish the cardiomyocyte-specific responses to high levels of BH4. Quantification of BH4 and BH2 in mGCH transgenic hearts showed age-based variations in BH4:BH2 ratios. Hearts of mice (<6 months) have lower BH4:BH2 ratios than hearts of older mice while both GTPCH activity and tissue ascorbate levels were higher in hearts of young than older mice. No evident changes in nitric oxide (NO) production assessed by nitrite and endogenous iron-nitrosyl complexes were detected in any of the age groups. Increased BH4 production in cardiomyocytes resulted in a significant loss of mitochondrial function. Diminished oxygen consumption and reserve capacity was verified in mitochondria isolated from hearts of 12-month old compared to 3-month old mice, even though at 12 months an improved BH4:BH2 ratio is established. Accumulation of 4 hydroxynonenal (4-HNE) and decreased glutathione levels were found in the mGCH hearts and isolated mitochondria. Taken together, our results indicate that the ratio of BH4:BH2 does not predict changes in neither NO levels nor cellular redox state in the heart. The BH4 oxidation essentially limits the capacity of cardiomyocytes to reduce oxidant stress. Cardiomyocyte with chronically high levels of BH4 show a significant decline in redox state and mitochondrial function. PMID- 26826577 TI - A case report demonstrating the utility of next generation sequencing in analyzing serial samples from the lung following an infection with influenza A (H7N9) virus. AB - BACKGROUND: Bacterial pneumonia is a well-recognized sequela of patient suffering from influenza, and a key factor, with cytokine dysregulation, that contribute to severe disease and mortality. OBJECTIVES: To obtain a comprehensive assessment of lung microbial community dynamics in a fatal influenza H7N9 case during the whole clinical course, we undertook a longitudinal study. STUDY DESIGN: Serial bronchoalveolar lavage fluid samples were collected from a H7N9 patient after illness onset, and the microbiome was characterized by using next-generation sequencing and microbiological approaches. Furthermore, the kinetics of circulating cytokine storms related to viral and secondary bacterial infection were analyzed. RESULTS: Within complex and dynamic communities, the lung microbiome with H7N9 infection were dominated by gram-negative bacteria, Acinetobacter baumannii after the viral invasion and during the whole clinical course. Sputum and blood culture confirmed the secondary bacterial infection with multidrug-resistant A. baumannii 9 days later. The dynamics of the bacterial infection with carbapenem-resistant A. baumannii correlated with antibiotic therapy. Our observations also indicated that sustained high levels of host inflammatory factors, consisting of a set of distinct cytokines associated with disease stage, may contribute to disease progression and death. CONCLUSIONS: This study demonstrates an initial attempt to explore the dynamic microbiome involved inH7N9 infection and its response to antimicrobial therapy, as well as host cytokine response to infection by using next-generation sequencing. These type of investigations with longitudinal follow-up to understand dynamics of microbial community and cytokines involved in lung infection may provide opportunities for development and optimization of targeted antimicrobial therapy and even new therapeutic strategies. PMID- 26826579 TI - Every cycle counts. PMID- 26826578 TI - Performance of genotypic algorithms for predicting tropism of HIV-1CRF02_AG subtype. AB - BACKGROUND: Several genotypic rules for predicting HIV-1 non-B subtypes tropism are commonly used, but there is no consensus about their performances. OBJECTIVES: Three genotypic methods were compared for CRF02_AG HIV-1 tropism determination. STUDY DESIGN: V3 env region of 178HIV-1 CRF02_AG from Pitie Salpetriere and Saint-Antoine Hospitals was sequenced from plasma HIV-1 RNA. HIV 1 tropism was determined by Geno2Pheno algorithm, false positive rate (FPR) 5% or 10%, the 11/25 rule or the combined criteria of the 11/25 and net charge rule. RESULTS: A concordance of 91.6% was observed between Geno2pheno 5% and the combined criteria. The results were nearly similar for the comparison between Geno2pheno 5% and the 11/25 rule. More mismatches were observed when Geno2pheno was used with the FPR 10%. A lower nadir CD4 cell count was associated with a discordance of tropism prediction between Geno2pheno 5% and the combined criteria or the 11/25 rule (p=0.02 and p=0.03, respectively). A lower HIV-1 viral load was associated with some discordance for the comparison of Geno2pheno 10% and the combined rule (p=0.02). CONCLUSION: Geno2pheno FPR 5% or 10% predicted more X4 tropic viruses for this set of CRF02_AG sequences than the combined criteria or the 11/25 rule alone. Furthermore, Geno2pheno FPR 5% was more concordant with the 11/25 rule and the combined rule than Geno2pheno 10% to predict HIV-1 tropism. Overall, Geno2pheno 5% could be used to predict CRF02_AG tropism as well as other genotypic rules. PMID- 26826580 TI - Reply: Every cycle counts. PMID- 26826581 TI - Design and discovery of 4-anilinoquinazoline-acylamino derivatives as EGFR and VEGFR-2 dual TK inhibitors. AB - Both EGFR and VEGFR-2 are important targets for cancer therapy, the combined inhibition of both EGFR and VEGFR-2 signaling pathway represents a promising approach to the treatment of cancers with a synergistic effect. In this study, a series of novel 4-anilinoquinazoline-acylamino derivatives designed as EGFR and VEGFR-2 dual inhibitors were synthesized and evaluated for biological activities. Most of them exhibited interesting inhibitory potencies against EGFR and VEGFR-2 as well as good antiproliferative activities. Compounds 15a, 15b and 15e exhibited the most potent inhibitory activity against EGFR (IC50 = 0.13 MUM, 0.15 MUM and 0.69 MUM, respectively) and VEGFR-2 (IC50 = 0.56 MUM, 1.81 MUM and 0.87 MUM, respectively), among them, compound 15b showed the highest antiproliferative activities against three cancer cell lines (HT-29, MCF-7 and H460) with IC50 of 5.27 MUM, 4.41 MUM and 11.95 MUM, respectively. Molecular docking established the interaction of 15a with the DFG-out conformation of VEGFR-2, suggesting that they might be type II kinase inhibitors. PMID- 26826582 TI - The importance of triazole scaffold in the development of anticonvulsant agents. AB - Epilepsy is one of the most important neurological disorders with high prevalence worldwide. Many epileptic patients are not completely treated with available drugs and need multiple therapies. Also, many antiepileptic drugs have shown unwanted side effects and drug interactions. Therefore there are continuing interests to find new anticonvulsant drugs. Triazole ring has been found in the structure of many compounds with diverse biological effects. Due to the success of several triazole-containing drugs that entered the pharmaceutical market as CNS-active drugs, this class of heterocyclic compounds has great importance for discovery and development of new anticonvulsant drugs. In this article, we have tried to summarize the latest efforts which have been made in the design and development of triazole-derived anticonvulsant agents. PMID- 26826583 TI - Likelihood of Incomplete Kidney Tumor Ablation with Radio Frequency Energy: Degree of Enhancement Matters. AB - PURPOSE: Larger size and clear cell histopathology are associated with worse outcomes for malignant renal tumors treated with radio frequency ablation. We hypothesize that greater tumor enhancement may be a risk factor for radio frequency ablation failure due to increased vascularity. MATERIALS AND METHODS: A retrospective review of patients who underwent radio frequency ablation for renal tumors with contrast enhanced imaging available was performed. The change in Hounsfield units (HU) of the tumor from the noncontrast phase to the contrast enhanced arterial phase was calculated. Radio frequency ablation failure rates for biopsy confirmed malignant tumors were compared using the chi-squared test. Multivariate logistic analysis was performed to assess predictive variables for radio frequency ablation failure. Disease-free survival was calculated using Kaplan-Meier analysis. RESULTS: A total of 99 patients with biopsy confirmed malignant renal tumors and contrast enhanced imaging were identified. The incomplete ablation rate was significantly lower for tumors with enhancement less than 60 vs 60 HU or greater (0.0% vs 14.6%, p=0.005). On multivariate logistic regression analysis tumor enhancement 60 HU or greater (OR 1.14, p=0.008) remained a significant predictor of incomplete initial ablation. The 5-year disease-free survival for size less than 3 cm was 100% vs 69.2% for size 3 cm or greater (p <0.01), while 5-year disease-free survival for HU change less than 60 was 100% vs 92.4% for HU change 60 or greater (p=0.24). CONCLUSIONS: Biopsy confirmed malignant renal tumors, which exhibit a change in enhancement of 60 HU or greater, experience a higher rate of incomplete initial tumor ablation than tumors with enhancement less than 60 HU. Size 3 cm or greater portends worse 5 year disease-free survival after radio frequency ablation. The degree of enhancement should be considered when counseling patients before radio frequency ablation. PMID- 26826584 TI - Alpha synuclein protein is involved in Aluminum-induced cell death and oxidative stress in PC12 cells. AB - Increased expression and aggregation of alpha-synuclein (alpha-syn) protein plays a critical role in mediating the toxic effects of a number of neurodegenerative substances including metals. Thus, knockdown expression of alpha-syn is proposed as a possible modality for treatment of Parkinson disease (PD). Aluminum (Al) is a neurotoxic metal that contributes to pathogenesis of PD. The aim of this study was to investigate the role of alpha-syn protein in mediating Al-induced toxicity in PC12 cells. Specific alpha-syn small interference RNA (siRNA) was applied to knockdown the expression of alpha-syn protein in PC12 cells. The effects of different concentrations of Al-maltolate (Almal) were then evaluated on cell viability and oxidative stress in the alpha-syn downregulated cells. The results showed that Almal dose dependently induced apoptosis and increased malondialdehyde (MDA) and catalase activity in PC12 cells. Downregulation of alpha-syn protein significantly increased cell viability and decreased oxidative markers in Almal-treated cells. These findings suggest that alpha-syn protein may mediate Al-induced apoptosis and oxidative stress in PC12 cells. PMID- 26826585 TI - Suppression of outward K(+) currents by activating dopamine D1 receptors in rat retinal ganglion cells through PKA and CaMKII signaling pathways. AB - Dopamine plays an important role in regulating neuronal functions in the central nervous system by activating the specific G-protein coupled receptors. Both D1 and D2 dopamine receptors are extensively distributed in the retinal neurons. In the present study, we investigated the effects of D1 receptor signaling on outward K(+) currents in acutely isolated rat retinal ganglion cells (RGCs) by patch-clamp techniques. Extracellular application of SKF81297 (10 MUM), a specific D1 receptor agonist, significantly and reversibly suppressed outward K(+) currents of the cells, which was reversed by SCH23390 (10 MUM), a selective D1 receptor antagonist. We further showed that SKF81297 mainly suppressed the glybenclamide (Gb)- and 4-aminopyridine (4-AP)-sensitive K(+) current components, but did not show effect on the tetraethylammonium (TEA)-sensitive one. Both protein kinase A (PKA) and calcium/calmodulin-dependent protein kinase II (CaMKII) signaling pathways were likely involved in the SKF81297-induced suppression of the K(+) currents since either Rp-cAMP (10 MUM), a cAMP/PKA signaling inhibitor, or KN-93 (10 MUM), a specific CaMKII inhibitor, eliminated the SKF81297 effect. In contrast, neither protein kinase C (PKC) nor mitogen activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway seemed likely to be involved because both the PKC inhibitor bisindolylmaleimide IV (Bis IV) (10 MUM) and the MAPK/ERK1/2 inhibitor U0126 (10 MUM) did not block the SKF81297-induced suppression of the K(+) currents. These results suggest that activation of D1 receptors suppresses the Gb- and 4-AP sensitive K(+) current components in rat RGCs through the intracellular PKA and CaMKII signaling pathways, thus modulating the RGC excitability. PMID- 26826586 TI - Localization of Neurensin1 in cerebellar Purkinje cells of the developing chick and its possible function in dendrite formation. AB - Neurensin1 (Nrsn1) gene, highly specific to neurons, has been considered to play a role in neurite growth during neuronal development and regeneration in mice. Intense expression of Nrsn1 was found particularly in projecting neurons like retinal ganglion cells and spinal motor neurons, suggesting that Neurensin1 is needed for active neurite growth. In the present study we cloned chick Nrsn1 gene and produced an antibody against cNrsn1 to examine Nrsn1 localization in the chick brain, since the chick is a suitable animal model for the study of developmental neurobiology. We found that there are neurons intensely stained for Nrsn1 antibody localized in the optic tectum, the cerebellum and the brain stem. These neurons are large in size and considered to be projecting neurons. In the cerebellum, Purkinje cells are the only one type of neurons stained for Nrsn1. During Purkinje cell development the arborized dendrites and axons become intensely stained at stages E17-18. A siRNA gene knock down was applied to the cultured embryonic cerebellar tissues and the result showed that Nrsn1 has an important role in dendrite formation of Purkinje cells. These findings suggest that Neurensin1 is also involved in neural development in the chick brain and that the embryonic chick brain is a good model to disclose the molecular and physiological functions of Nrsn1. PMID- 26826587 TI - Detrusor-External Sphincter Dyssynergia: Review of Minimally Invasive and Endoscopic Management. AB - Detrusor-external sphincter dyssynergia (DSD) is a debilitating problem in patients with spinal cord injury. DSD carries a high risk of complications, and even life expectancy can be affected. Management of this condition includes the use of antimuscarinic agents in combination with intermittent catheterization, indwelling urethral catheterization, suprapubic catheterization, and a variety of surgical options, depending on patient and physician preference. This paper will review the current literature and data on minimally invasive and endoscopic management of DSD. PMID- 26826588 TI - Subpubic Cartilaginous Cyst--A Rare Periurethral Lesion With Implications for Surgical Approach. PMID- 26826589 TI - A Rare Anatomical Variant of Spermatic Vein as Cause of Recurrence After Surgical Correction of Varicocele. AB - Varicocele may be treated with many different modalities, including radiologic and surgical approaches, but what is the best treatment remains controversial. The recurrence rate following varicocele repair ranges from 0.6% to 35% depending upon the technique used. We describe in detail a rare anatomical variant of the left internal spermatic veins and the appropriate treatment of recurrent varicocele with percutaneous scleroembolization. In case of recurrent varicocele after surgical repair, knowledge of anatomical variability of internal spermatic veins is essential for treatment planning. PMID- 26826590 TI - Intravesical Prostatic Protrusion as a Predicting Factor for the Adverse Clinical Outcome in Patients With Symptomatic Benign Prostatic Enlargement Treated With Dutasteride. AB - OBJECTIVE: To evaluate the role of intravesical prostatic protrusion (IPP) as a predictive factor for adverse clinical outcomes in patients treated with dutasteride for lower urinary tract symptoms secondary to benign prostatic enlargement (BPE). METHODS: In total, 111 patients treated with dutasteride for symptomatic BPE were analyzed. Stepwise multivariate logistic regression was applied to evaluate predictors for acute urinary retention (AUR) or benign prostatic hyperplasia (BPH)-related surgery. We applied an IPP cutoff value of 10 mm. The clinical variables were assessed using univariate analysis. RESULTS: Of 111 patients, 27 (24.3%) developed AUR or required surgical intervention. On multivariate analysis, IPP remained as the independent predictor for AUR and need for BPH-related surgery (odds ratio, 1.27; P < .001). Both international prostate symptom score and maximum urinary flow rate significantly improved in patients with low IPP (P = .03 and P < .001, respectively), but not in those with high IPP. No significant reduction was found in the degree of IPP despite the significant reduction in prostate volume after dutasteride treatment (P = .84 and P < .001, respectively). The 3-year cumulative incidence of AUR or BPH related surgery in the low IPP group vs the high IPP group was 9.9% vs 71.5%, respectively (P < .001). CONCLUSION: High IPP is associated with a higher risk of treatment resistance, AUR, or the need for prostatic surgery in patients receiving dutasteride treatment for symptomatic BPE. Dutasteride might not be effective for IPP reduction. PMID- 26826591 TI - Redox-coupled substrate water reorganization in the active site of Photosystem II The role of calcium in substrate water delivery. AB - Photosystem II (PSII) catalyzes light-driven water splitting in nature and is the key enzyme for energy input into the biosphere. Important details of its mechanism are not well understood. In order to understand the mechanism of water splitting, we perform here large-scale density functional theory (DFT) calculations on the active site of PSII in different oxidation, spin and ligand states. Prior to formation of the O-O bond, we find that all manganese atoms are oxidized to Mn(IV) in the S3 state, consistent with earlier studies. We find here, however, that the formation of the S3 state is coupled to the movement of a calcium-bound hydroxide (W3) from the Ca to a Mn (Mn1 or Mn4) in a process that is triggered by the formation of a tyrosyl radical (Tyr-161) and its protonated base, His-190. We find that subsequent oxidation and deprotonation of this hydroxide on Mn1 result in formation of an oxyl-radical that can exergonically couple with one of the oxo-bridges (O5), forming an O-O bond. When O(2) leaves the active site, a second Ca-bound water molecule reorients to bridge the gap between the manganese ions Mn1 and Mn4, forming a new oxo-bridge for the next reaction cycle. Our findings are consistent with experimental data, and suggest that the calcium ion may control substrate water access to the water oxidation sites. PMID- 26826592 TI - Combining high-throughput MALDI-TOF mass spectrometry and isoelectric focusing gel electrophoresis for virtual 2D gel-based proteomics. AB - The virtual two-dimensional gel electrophoresis/mass spectrometry (virtual 2D gel/MS) technology combines the premier, high-resolution capabilities of 2D gel electrophoresis with the sensitivity and high mass accuracy of mass spectrometry (MS). Intact proteins separated by isoelectric focusing (IEF) gel electrophoresis are imaged from immobilized pH gradient (IPG) polyacrylamide gels (the first dimension of classic 2D-PAGE) by matrix-assisted laser desorption/ionization (MALDI) MS. Obtaining accurate intact masses from sub-picomole-level proteins embedded in 2D-PAGE gels or in IPG strips is desirable to elucidate how the protein of one spot identified as protein 'A' on a 2D gel differs from the protein of another spot identified as the same protein, whenever tryptic peptide maps fail to resolve the issue. This task, however, has been extremely challenging. Virtual 2D gel/MS provides access to these intact masses. Modifications to our matrix deposition procedure improve the reliability with which IPG gels can be prepared; the new procedure is described. Development of this MALDI MS imaging (MSI) method for high-throughput MS with integrated 'top down' MS to elucidate protein isoforms from complex biological samples is described and it is demonstrated that a 4-cm IPG gel segment can now be imaged in approximately 5min. Gel-wide chemical and enzymatic methods with further interrogation by MALDI MS/MS provide identifications, sequence-related information, and post-translational/transcriptional modification information. The MSI-based virtual 2D gel/MS platform may potentially link the benefits of 'top down' and 'bottom-up' proteomics. PMID- 26826593 TI - Further evidence for the role of histamine H3, but not H1, H2 or H4, receptors in immepip-induced inhibition of the rat cardioaccelerator sympathetic outflow. AB - Since histamine H3 and H4 receptors are coupled to heterotrimeric Gi/o proteins, a signal transduction pathway associated with inhibition of neurotransmitter release, the present study has investigated the inhibition of the rat cardioaccelerator sympathetic outflow induced by the H3/H4 receptor agonist immepip by using antagonists for histamine H1 (ketotifen), H2 (ranitidine), H3 (thioperamide) and H4 (JNJ7777120) receptors. For this purpose, 102 male Wistar rats were pithed, artificially ventilated and prepared for either preganglionic spinal (C7-T1) stimulation of the cardioaccelerator sympathetic outflow (n=90) or i.v. bolus injections of noradrenaline (n=12). This approach resulted in frequency-dependent and dose-dependent tachycardic responses, respectively. I.v. continuous infusions of immepip (3 and 10 MUg/kg min), but not of saline (0.02 ml/min), dose-dependently inhibited the sympathetically-induced tachycardic responses. Moreover, the cardiac sympatho-inhibition induced by 10 MUg/kg min immepip (which failed to affect the tachycardic responses to i.v. noradrenaline) was: (i) unaltered after i.v. treatment with 1 ml/kg vehicle, 100 MUg/kg ketotifen, 3000 MUg/kg ranitidine, 30 MUg/kg thioperamide or 300 MUg/kg JNJ7777120; and (ii) abolished after 100 MUg/kg thioperamide (i.v.). These doses of antagonists, which did not affect per se the sympathetically-induced tachycardic responses, were high enough to block their respective receptors. In conclusion, the cardiac sympatho-inhibition induced by 10 MUg/kg.min immepip involves histamine H3 receptors, with further pharmacological evidence excluding the involvement of H1, H2 and H4 receptors. PMID- 26826594 TI - Apigenin reverses depression-like behavior induced by chronic corticosterone treatment in mice. AB - Previous researches found that apigenin exerted antidepressant-like effects in rodents. However, it is unclear whether the neurotrophic system is involved in the antidepressant-like effects of apigenin. Our present study aimed to explore the neurotrophic related mechanism of apigenin in depressive-like mice induced by chronic corticosterone treatment. Mice were repeatedly injected with corticosterone (40 mg/kg) subcutaneously (s.c) once daily for consecutive 21 days. Apigenin (20 and 40 mg/kg) and fluoxetine (20 mg/kg) were administered 30 min prior to the corticosterone injection. The behavioral tests indicated that apigenin reversed the reduction of sucrose preference and the elevation of immobility time in mice induced by chronic corticosterone treatment. In addition, the increase in serum corticosterone levels and the decrease in hippocampal brain derived neurotrophic factor (BDNF) levels in corticosterone-treated mice were also ameliorated by apigenin administration. Taken together, our findings intensively confirmed the antidepressant-like effects of apigenin and indicated that the antidepressant-like mechanism of apigenin was mediated, at least partly by up-regulation of BDNF levels in the hippocampus. PMID- 26826595 TI - Verification of measles elimination in Australia: Application of World Health Organization regional guidelines. AB - BACKGROUND: The World Health Organization (WHO) Western Pacific Region (WPR) Guidelines on verification of measles elimination were established in 2012. This article outlines Australia's approach to addressing the guideline's five lines of evidence, which led to formal verification of elimination by the WHO Regional Verification Commission (RVC) in March 2014. METHODS: The criteria were addressed using national measles notifications, data from selected laboratories, the national childhood immunization register, and three national serosurveys (1998/1999, 2002, 2007). RESULTS: Australia met or exceeded all indicator targets with either national or sentinel data. Laboratory and epidemiological surveillance were of high quality, with 85% of cases documented as imported/import-related (target 80%); coverage with the first dose of measles vaccine was close to 94% in 2008-2012 and second dose coverage increased to 91% in 2012 (target >95%). There is ongoing commitment by the Australian Government to increase immunization coverage, and the absence of sustained transmission of any single measles genotype was demonstrated. CONCLUSIONS: This is the first documentation of the successful application of the WPR RVC guidelines. The indicators afford some flexibility but appear to provide appropriate rigor to judge achievement of measles elimination. Our experience could assist other countries seeking to verify their elimination status. PMID- 26826596 TI - Democracy predicts sport and recreation membership: Insights from 52 countries. AB - Although evidence suggests sport and recreation are powerful contributors to worldwide public health, sizable gender differences persist. It is unknown whether country characteristics moderate gender differences across countries. The primary purpose of this study was to examine if countries' levels of democracy and/or gender inequality moderate gender differences in sport and recreation membership across countries. The secondary purpose was to examine if democracy and/or gender inequality predicts overall rates of sport and recreation membership for both males and females. This study involved a nested cross sectional design and employed the sixth wave (2013) of the world value survey (nSs=71,901, ncountries=52). Multiple hierarchal nonlinear Bernoulli models tested: (1) if countries' levels of democracy moderate gender differences in sport and recreation membership; and (2) if democracy is associated with increased sport and recreation membership for both males and females. Countries' level of democracy fully moderated gender differences in sport and recreation membership across countries. Moreover, democracy was positively associated with both male and female membership, even when controlling for individual and country level covariates. Democratic political regimes may confer health benefits via increased levels of sport and recreation membership, especially for females. Future research should test mediating mechanisms. PMID- 26826597 TI - Characterization of clinical and immunological features in patients coinfected with dengue virus and HIV. AB - The pathogenesis of dengue in subjects coinfected with HIV remains largely unknown. We investigate clinical and immunological parameters in coinfected DENV/HIV patients. According to the new dengue classification, most coinfected DENV/HIV patients presented mild clinical manifestations of dengue infection. Herein, we show that DENV/HIV coinfected patients had higher CD8 T cells percentages reflected as a lower CD4/CD8 ratio. Furthermore, CCR5 expression on CD4 T cells and CD107a expression on both T subsets were significantly higher in coinfected patients when compared with monoinfected DENV and HIV individuals respectively. Increased inflammatory response was observed in treated HAART coinfected patients despite undetectable HIV load. These data indicate that DENV infection may influence the clinical profile and immune response in individuals concomitantly infected with HIV. PMID- 26826599 TI - Photoperiod regulates growth of male accessory glands through juvenile hormone signaling in the linden bug, Pyrrhocoris apterus. AB - Adult reproductive diapause is characterized by lower behavioral activity, ceased reproduction and absence of juvenile hormone (JH). The role of JH receptor Methoprene-tolerant (Met) in female reproduction is well established; however, its function in male reproductive development and behavior is unclear. In the bean bug, Riptortus pedestris, circadian genes are essential for mediating photoperiodically-dependent growth of the male accessory glands (MAGs). The present study explores the role of circadian genes and JH receptor in male diapause in the linden bug, Pyrrhocoris apterus. These data indicate that circadian factors Clock, Cycle and Cry2 are responsible for photoperiod measurement, whereas Met and its partner protein Taiman participate in JH reception. Surprisingly, knockdown of the JH receptor neither lowered locomotor activity nor reduced mating behavior of males. These data suggest existence of a parallel, JH-independent or JH-upstream photoperiodic regulation of reproductive behavior. PMID- 26826598 TI - Early BAFF receptor blockade mitigates murine Sjogren's syndrome: Concomitant targeting of CXCL13 and the BAFF receptor prevents salivary hypofunction. AB - Sjogren's syndrome (SS) is a debilitating autoimmune disease. Patients with SS may develop xerostomia. This process is progressive, and there are no therapeutics that target disease etiology. We hypothesized BAFF receptor (BAFFR) blockade would mitigate SS disease development, and neutralization of CXCL13 and BAFF signaling would be more efficacious than BAFFR blockade alone. We treated NOD/ShiLtJ SS mice with soluble BAFF receptor (BAFFR-Fc) or anti-CXCL13/BAFFR-Fc in combination, prior to the development of clinical disease. Our results show treatment with BAFFR-Fc reduced peripheral B cell numbers and decreased sialadenitis. In addition, this treatment reduced total serum immunoglobulin as well as IgG and IgM specific anti-nuclear autoantibodies. NOD/ShiLtJ mice treated with BAFFR-Fc and anti-CXCL13 antibody were protected from salivary deficits. Results from this study suggest blockade of CXCL13 and BAFFR together may be an effective therapeutic strategy in preventing salivary hypofunction and reducing autoantibody titers and sialadenitis in patients with SS. PMID- 26826600 TI - The C2 protein of tomato yellow leaf curl Sardinia virus acts as a pathogenicity determinant and a 16-amino acid domain is responsible for inducing a hypersensitive response in plants. AB - The role of the C2 protein in the pathogenicity of tomato yellow leaf curl Sardinia virus (TYLCSV) was investigated. Here we report that Agrobacterium mediated transient expression of TYLCSV C2 resulted in a strong hypersensitive response (HR) in Nicotiana benthamiana, N. tabacum, and Arabidopsis thaliana, with induction of plant cell death and production of H2O2. Since HR is not evident in plants infected by TYLCSV, it is expected that TYLCSV encodes a gene (or genes) that counters this response. HR was partially counteracted by co agroinfiltration of TYLCSV V2 and Rep, leading to chlorotic reaction, with no HR development. Considering that the corresponding C2 protein of the closely related tomato yellow leaf curl virus (TYLCV) did not induce HR, alignment of the C2 proteins of TYLCSV and TYLCV were carried out and a hypervariable region of 16 amino acids was identified. Its role in the induction of HR was demonstrated using TYLCSV-TYLCV C2 chimeric genes, encoding two TYLCSV C2 variants with a complete (16 aa) or a partial (10 aa only) swap of the corresponding sequence of TYLCV C2. Furthermore, using NahG transgenic N. benthamiana lines compromised in the accumulation of salicylic acid (SA), a key regulator of HR, only a chlorotic response occurred in TYLCSV C2-infiltrated tissue, indicating that SA participates in such plant defense process. These findings demonstrate that TYLCSV C2 acts as a pathogenicity determinant and induces host defense responses controlled by the SA pathway. PMID- 26826601 TI - Nuclear introns outperform mitochondrial DNA in inter-specific phylogenetic reconstruction: Lessons from horseshoe bats (Rhinolophidae: Chiroptera). AB - Despite many studies illustrating the perils of utilising mitochondrial DNA in phylogenetic studies, it remains one of the most widely used genetic markers for this purpose. Over the last decade, nuclear introns have been proposed as alternative markers for phylogenetic reconstruction. However, the resolution capabilities of mtDNA and nuclear introns have rarely been quantified and compared. In the current study we generated a novel ~5kb dataset comprising six nuclear introns and a mtDNA fragment. We assessed the relative resolution capabilities of the six intronic fragments with respect to each other, when used in various combinations together, and when compared to the traditionally used mtDNA. We focused on a major clade in the horseshoe bat family (Afro-Palaearctic clade; Rhinolophidae) as our case study. This old, widely distributed and speciose group contains a high level of conserved morphology. This morphological stasis renders the reconstruction of the phylogeny of this group with traditional morphological characters complex. We sampled multiple individuals per species to represent their geographic distributions as best as possible (122 individuals, 24 species, 68 localities). We reconstructed the species phylogeny using several complementary methods (partitioned Maximum Likelihood and Bayesian and Bayesian multispecies-coalescent) and made inferences based on consensus across these methods. We computed pairwise comparisons based on Robinson-Foulds tree distance metric between all Bayesian topologies generated (27,000) for every gene(s) and visualised the tree space using multidimensional scaling (MDS) plots. Using our supported species phylogeny we estimated the ancestral state of key traits of interest within this group, e.g. echolocation peak frequency which has been implicated in speciation. Our results revealed many potential cryptic species within this group, even in taxa where this was not suspected a priori and also found evidence for mtDNA introgression. We demonstrated that by using just two introns one can recover a better supported species tree than when using the mtDNA alone, despite the shorter overall length of the combined introns. Additionally, when combining any single intron with mtDNA, we showed that the result is highly similar to the mtDNA gene tree and far from the true species tree and therefore this approach should be avoided. We caution against the indiscriminate use of mtDNA in phylogenetic studies and advocate for pilot studies to select nuclear introns. The selection of marker type and number is a crucial step that is best based on critical examination of preliminary or previously published data. Based on our findings and previous publications, we recommend the following markers to recover phylogenetic relationships between recently diverged taxa (<20 My) in bats and other mammals: ACOX2, COPS7A, BGN, ROGDI and STAT5A. PMID- 26826602 TI - First multigene analysis of Archamoebae (Amoebozoa: Conosa) robustly reveals its phylogeny and shows that Entamoebidae represents a deep lineage of the group. AB - Archamoebae is an understudied group of anaerobic free-living or endobiotic protists that constitutes the major anaerobic lineage of the supergroup Amoebozoa. Hitherto, the phylogeny of Archamoebae was based solely on SSU rRNA and actin genes, which did not resolve relationships among the main lineages of the group. Because of this uncertainty, several different scenarios had been proposed for the phylogeny of the Archamoebae. In this study, we present the first multigene phylogenetic analysis that includes members of Pelomyxidae, and Rhizomastixidae. The analysis clearly shows that Mastigamoebidae, Pelomyxidae and Rhizomastixidae form a clade of mostly free-living, amoeboid flagellates, here called Pelobiontida. The predominantly endobiotic and aflagellated Entamoebidae represents a separate, deep-branching lineage, Entamoebida. Therefore, two unique evolutionary events, horizontal transfer of the nitrogen fixation system from bacteria and transfer of the sulfate activation pathway to mitochondrial derivatives, predate the radiation of recent lineages of Archamoebae. The endobiotic lifestyle has arisen at least three times independently during the evolution of the group. We also present new ultrastructural data that clarifies the primary divergence among the family Mastigamoebidae which had previously been inferred from phylogenetic analyses based on SSU rDNA. PMID- 26826603 TI - Phylogenetic analyses of gazelles reveal repeated transitions of key ecological traits and provide novel insights into the origin of the genus Gazella. AB - African bovids are a famous example of a taxonomic group in which the correlated evolution of body size, feeding mode, gregariousness, and social organization in relation to the preferred habitat type has been investigated. A continuum has been described ranging from small-bodied, sedentary, solitary or socially monogamous, forest- or bush-dwelling, browsing species that seek shelter from predation in dense vegetation, to large-bodied, migratory, highly gregarious, grazing taxa inhabiting open savannahs and relying on flight or group-defense behaviors when facing predators. Here, we examined a geographically widespread clade within the Bovidae (the genus Gazella) that shows minimal interspecific variation in body size and asked if we could still uncover correlated changes of key ecological and behavioral traits during repeated transitions from open-land to mountain-dwelling. Our study used a multi-locus phylogeny (based on sequence variation of Cytb and six nuclear intron markers) of all extant members of the genus Gazella to infer evolutionary patterns of key ecological and behavioral traits and to estimate ancestral character states using Bayesian inference. At the base of the Gazella-phylogeny, open plains were inferred as the most likely habitat type, and three independent transitions toward mountain-dwelling were uncovered. Those shifts coincided with shifts from migratory to sedentary lifestyles. Character estimation for group size was largely congruent with movement patterns in that species forming large groups tended to be migratory, while small group size was correlated with a sedentary lifestyle. Evolutionary patterns of two other conspicuous traits (twinning ability vs. exclusive singleton births and hornless vs. horned females) did not follow this trend in the Gazella-phylogeny. Furthermore, we inferred the genus Gazella to have emerged in the Late Miocene to Pliocene (10-3Mya), and estimating ancestral ranges based on a Dispersal-Extinction-Cladogenesis model found the Middle East to be the most likely origin of the genus. PMID- 26826604 TI - Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders. AB - Dextromethorphan (DM) is a commonly used antitussive and is currently the only FDA-approved pharmaceutical treatment for pseudobulbar affect. Its safety profile and diverse pharmacologic actions in the central nervous system have stimulated new interest for repurposing it. Numerous preclinical investigations and many open-label or blinded clinical studies have demonstrated its beneficial effects across a variety of neurological and psychiatric disorders. However, the optimal dose and safety of chronic dosing are not fully known. This review summarizes the preclinical and clinical effects of DM and its putative mechanisms of action, focusing on depression, stroke, traumatic brain injury, seizure, pain, methotrexate neurotoxicity, Parkinson's disease and autism. Moreover, we offer suggestions for future research with DM to advance the treatment for these and other neurological and psychiatric disorders. PMID- 26826605 TI - Differential motivational profiles following adolescent sucrose access in male and female rats. AB - Adolescents are the highest consumers of sugar sweetened drinks. Excessive consumption of such drinks is a likely contributor to the development of obesity and may be associated with enduring changes in the systems involved in reward and motivation. We examined the impact of daily sucrose consumption in young male and female rats (N=12 per group) across the adolescent period on the motivation to perform instrumental responses to gain food rewards as adults. Rats were or were not exposed to a sucrose solution for 2 h each day for 28 days across adolescence [postnatal days (P) 28-56]. They were then trained as adults (P70 onward) to lever press for a palatable 15% cherry flavored sucrose reward and tested on a progressive ratio (PR) schedule to assess motivation to respond for reinforcement. Female rats exposed to sucrose had higher breakpoints on the PR schedule than controls, whereas male rats exposed to sucrose had lower breakpoints than controls. These results show that consumption of sucrose during adolescence produced sex-specific behavioral changes in responding for sucrose as adults. PMID- 26826606 TI - Generalization of force-field adaptation in proprioceptively-deafferented subjects. AB - Humans have the remarkable ability to adapt their motor behaviour to changes in body properties and/or environmental conditions, based on sensory feedback such as vision and proprioception. The role of proprioception has been highlighted for the adaptation to new upper-limb dynamics, which is known to generalize to the opposite, non-adapted limb in healthy individuals. Such interlimb transfer seems to depend on sensory feedback, and the present study assessed whether the chronic loss of proprioception precludes interlimb transfer of dynamic adaptation by testing two well-characterized proprioceptively-deafferented subjects. These had to reach toward visual targets with vision of the limb. For both deafferented subjects, we observed adaptation of the dominant arm to Coriolis forces and after effects on non-dominant arm movements in different movement directions, thus indicating interlimb transfer. Overall, our findings show that motor learning can generalize across limbs and movement directions despite the loss of proprioceptive afferents. PMID- 26826607 TI - Monitoring transcranial direct current stimulation induced changes in cortical excitability during the serial reaction time task. AB - The measurement of the motor evoked potential (MEP) amplitudes using single pulse transcranial magnetic stimulation (TMS) is a common method to observe changes in motor cortical excitability. The level of cortical excitability has been shown to change during motor learning. Conversely, motor learning can be improved by using anodal transcranial direct current stimulation (tDCS). In the present study, we aimed to monitor cortical excitability changes during an implicit motor learning paradigm, a version of the serial reaction time task (SRTT). Responses from the first dorsal interosseous (FDI) and forearm flexor (FLEX) muscles were recorded before, during and after the performance of the SRTT. Online measurements were combined with anodal, cathodal or sham tDCS for the duration of the SRTT. Negative correlations between the amplitude of online FDI MEPs and SRTT reaction times (RTs) were observed across the learning blocks in the cathodal condition (higher average MEP amplitudes associated with lower RTs) but no significant differences in the anodal and sham conditions. tDCS did not have an impact on SRTT performance, as would be predicted based on previous studies. The offline before-after SRTT MEP amplitudes showed an increase after anodal and a tendency to decrease after cathodal stimulation, but these changes were not significant. The combination of different interventions during tDCS might result in reduced efficacy of the stimulation that in future studies need further attention. PMID- 26826609 TI - The role of the immune system in cancer: From mechanisms to clinical applications. PMID- 26826608 TI - Initiation and exclusivity of breastfeeding: association with mothers' and fathers' prenatal and postnatal depression and marital distress. AB - INTRODUCTION: This study explored the effects of mothers' and fathers' prenatal and postnatal depressive symptoms and marital distress on breastfeeding initiation and exclusive breastfeeding (EBF) duration. MATERIAL AND METHODS: This was a prospective follow-up of a cohort sample of 873 families participating to an intensive follow-up cohort of longitudinal Steps to the Healthy Development and Well-being of Children study (The STEPS study) in Southwestern Finland. The depressive symptoms were evaluated by The Edinburgh Postpartum Depression Scale and marital distress by the Revised Dyadic Adjustment Scale at 20th gestational week and at 4 months postpartum. EBF was self-reported real-time and defined as an infant receiving no food or drink other than mother's breast milk since birth, except occasionally water. RESULTS: Neither parents' prenatal depressive symptoms predicted breastfeeding initiation or EBF duration. The mothers' prenatal depressive symptoms, in turn, predicted their postnatal depressive symptoms, which were associated with shorter duration of EBF. The EBF duration was shortest amongst the mothers who had depressive symptoms both pre- and postnatally compared to mothers who had depressive symptoms only in either time point alone (M = 1.54, 2.06 and 2.04 months, respectively). Higher prenatal maternal marital distress was associated with longer EBF duration. CONCLUSIONS: The findings suggest that the continuity of maternal depressive symptoms throughout the perinatal period has adverse effect on EBF duration. Identification and treatment of mothers' depressive symptoms already during the prenatal period may improve breastfeeding practices. The finding of mothers' marital distress having positive impact on breastfeeding practices requires further investigation. PMID- 26826610 TI - Insights into natural products biosynthesis from analysis of 490 polyketide synthases from Fusarium. AB - Species of the fungus Fusarium collectively cause disease on almost all crop plants and produce numerous natural products (NPs), including some of the mycotoxins of greatest concern to agriculture. Many Fusarium NPs are derived from polyketide synthases (PKSs), large multi-domain enzymes that catalyze sequential condensation of simple carboxylic acids to form polyketides. To gain insight into the biosynthesis of polyketide-derived NPs in Fusarium, we retrieved 488 PKS gene sequences from genome sequences of 31 species of the fungus. In addition to these apparently functional PKS genes, the genomes collectively included 81 pseudogenized PKS genes. Phylogenetic analysis resolved the PKS genes into 67 clades, and based on multiple lines of evidence, we propose that homologs in each clade are responsible for synthesis of a polyketide that is distinct from those synthesized by PKSs in other clades. The presence and absence of PKS genes among the species examined indicated marked differences in distribution of PKS homologs. Comparisons of Fusarium PKS genes and genes flanking them to those from other Ascomycetes provided evidence that Fusarium has the genetic potential to synthesize multiple NPs that are the same or similar to those reported in other fungi, but that have not yet been reported in Fusarium. The results also highlight ways in which such analyses can help guide identification of novel Fusarium NPs and differences in NP biosynthetic capabilities that exist among fungi. PMID- 26826612 TI - Laparoscopic cholecystectomy during pregnancy: A systematic review of 590 patients. AB - BACKGROUND: The incidence of symptomatic biliary disease during pregnancy ranges from 0.05 to 8%. Cholecystectomy is one of the common operations performed during pregnancy and laparoscopic approach has gained popularity as an attractive alternative to open surgery. METHODS: In order to evaluate the safety, feasibility, outcomes and technical aspects of laparoscopic cholecystectomy during pregnancy a comprehensive search of Medline and Cohrane Library databases was conducted. RESULTS: Fifty-one studies were deemed eligible, in which laparoscopic cholecystectomy was attempted in 590 patients. The majority of the procedures (70.7%) were performed during the second trimester. Intraoperative and postoperative complications were observed in 3.5% and 4% of the study population. Conversion rate to open surgery was 2.2%. Fetal loss rate and preterm delivery rate were 0.4% and 5.7% respectively. CONCLUSION: Laparoscopic cholecystectomy seems to be a safe alternative to open surgery during pregnancy. PMID- 26826611 TI - VIP and PACAP analogs regulate therapeutic targets in high-risk neuroblastoma cells. AB - Neuroblastoma (NB) is a pediatric cancer. New therapies for high-risk NB aim to induce cell differentiation and to inhibit MYCN and ALK signaling in NB. The vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase activating polypeptide (PACAP) are 2 related neuropeptides sharing common receptors. The level of VIP increases with NB differentiation. Here, the effects of VIP and PACAP analogs developed for therapeutic use were studied in MYCN amplified NB SK-N-DZ and IMR-32 cells and in Kelly cells that in addition present the F1174L ALK mutation. As previously reported by our group in IMR-32 cells, VIP induced neuritogenesis in SK-N-DZ and Kelly cells and reduced MYCN expression in Kelly but not in SK-N-DZ cells. VIP decreased AKT activity in the ALK-mutated Kelly cells. These effects were PKA-dependent. IMR-32, SK-NDZ and Kelly cells expressed the genes encoding the 3 subtypes of VIP and PACAP receptors, VPAC1, VPAC2 and PAC1. In parallel to its effect on MYCN expression, VIP inhibited invasion in IMR-32 and Kelly cells. Among the 3 PACAP analogs tested, [Hyp(2)]PACAP-27 showed higher efficiency than VIP in Kelly cells. These results indicate that VIP and PACAP analogs act on molecular and cellular processes that could reduce aggressiveness of high-risk NB. PMID- 26826613 TI - Effects of the SLCO1B1 *1 and SLCO1B1 *5 polymorphisms on IL-6 and IL-10 levels in patients under pravastatin treatment prior to inguinal hernia repair. AB - BACKGROUND: Different genetic variants in the SLCO1B1 gene have been shown to have functional importance in individual variability in pravastatin pharmacokinetics, resulting in different inflammatory responses to surgical inguinal hernia repair. The aim of this study was to determine IL-6 and IL-10 serum concentrations in the presence and absence of the SLCO1B1*1 and SLCO1B1*5 polymorphisms in patients under pravastatin treatment that underwent inguinal hernia repair. METHODS: The study included 26 subjects that were under pravastatin treatment (40 mg/day) at least 1 month prior to inguinal hernia repair open technique. All the subjects were genotyped for the SLCO1B1*1 and SLCO1B1*5 polymorphisms through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and their preoperative and postoperative serum IL 6 and IL-10 levels were quantified through the ELISA technique. The IL-6 and IL 10 levels were analyzed in the presence or absence of the mutated polymorphism for SLCO1B1*1 and SLCO1B1*5. RESULTS: The SLCO1B1*1 polymorphism had a frequency of 38.5% and the SLCO1B1*5 polymorphism had a frequency of 19.2%. The preoperative and postoperative serum concentrations of IL-6 were 0.252 pg/ml +/- 0.19 and 0.206 pg/ml +/- 0.20, respectively, with a p = 0.525, whereas the preoperative and postoperative serum concentrations for IL-10 were 4.943 pg/ml +/ 3.13 and 4.611 pg/ml +/- 3.01, respectively, with a p = 0.004. CONCLUSIONS: The patients under pravastatin treatment presented with lower postoperative IL-10 levels with respect to the baseline concentration (p = 0.004), regardless of the presence or absence of the two polymorphisms. PMID- 26826614 TI - Repeated evolution of carnivory among Indo-Australian rodents. AB - Convergent evolution, often observed in island archipelagos, provides compelling evidence for the importance of natural selection as a generator of species and ecological diversity. The Indo-Australian Archipelago (IAA) is the world's largest island system and encompasses distinct biogeographic units, including the Asian (Sunda) and Australian (Sahul) continental shelves, which together bracket the oceanic archipelagos of the Philippines and Wallacea. Each of these biogeographic units houses numerous endemic rodents in the family Muridae. Carnivorous murids, that is those that feed on animals, have evolved independently in Sunda, Sulawesi (part of Wallacea), the Philippines, and Sahul, but the number of origins of carnivory among IAA murids is unknown. We conducted a comprehensive phylogenetic analysis of carnivorous murids of the IAA, combined with estimates of ancestral states for broad diet categories (herbivore, omnivore, and carnivore) and geographic ranges. These analyses demonstrate that carnivory evolved independently four times after overwater colonization, including in situ origins on the Philippines, Sulawesi, and Sahul. In each biogeographic unit the origin of carnivory was followed by evolution of more specialized carnivorous ecomorphs such as vermivores, insectivores, and amphibious rats. PMID- 26826615 TI - Human Adipose-Derived Mesenchymal Stromal/Stem Cells Remain Viable and Metabolically Active Following Needle Passage. AB - OBJECTIVE: To assess the biological effects of passage through clinically relevant needles on the viability and metabolic activity of culture-expanded, human adipose tissue-derived mesenchymal stromal/stem cells (AMSCs). DESIGN: Prospective observational pilot study. SETTING: Academic medical center. PARTICIPANTS: Patient-derived clinical-grade culture expanded AMSCs. INTERVENTIONS: AMSCs were passed through syringes without a needle attached (control), with an 18-gauge (25.4-mm) needle attached and with a 30-gauge (19-mm) needle attached at a constant injection flow rate and constant cell concentrations. Each injection condition was completed in triplicate. MAIN OUTCOME MEASURES: Cell number and viability, proliferative capacity, metabolic activity, and acute gene expression as measured by cell counts, mitochondrial activity, and quantitative real time reverse-transcription polymerase chain reaction on day 0 (immediately), day 1, and day 4 after injection. RESULTS: AMSC viability was not significantly affected by injection, and cells proliferated normally regardless of study group. Postinjection, AMSCs robustly expressed both proliferation markers and extracellular matrix proteins. Stress-response mRNAs were markedly but transiently increased independently of needle size within the first day in culture postinjection. CONCLUSIONS: Human, culture-expanded AMSCs maintain their viability, proliferative capacity, and metabolic function following passage through needles as small as 30-gauge at constant flow rates of 4 mL/min, despite an early, nonspecific stress/cytoprotective response. These initial findings suggest that culture-expanded AMSCs should tolerate the injection process during most cell-based therapeutic interventions. PMID- 26826616 TI - Peripheral Neuropathy After Fecal Microbiota Transplantation for Clostridium difficile Infection: A Case Report. AB - We present a case of a 71-year-old man with Clostridium difficile infection who underwent fecal transplantation. The patient was found to have a predominantly demyelinating sensorimotor peripheral polyneuropathy upon electrodiagnostic testing. To our knowledge, only one case of peripheral neuropathy after fecal transplantation has previously been reported. Although the exact cause of this patient's neuropathy cannot be confirmed, it has been speculated that the pathophysiology is an immune-mediated process. Given the increasing incidence of C difficile infections and the emergence of fecal transplantation as treatment, it is important to note that peripheral neuropathy is a potential adverse complication. PMID- 26826617 TI - The Effect of Body Mass Index on Fluoroscopic Time and Radiation Dose During Intra-articular Hip Injections. AB - BACKGROUND: Intra-articular hip injections are commonly performed for both diagnostic and therapeutic interventions. Because of the risk of damage to neurovascular structures, fluoroscopic guidance with injection of contrast material has been established as the gold standard to ensure proper needle placement into the intra-articular space. However, fluoroscopically guided intra articular hip injections put patients at risk due to radiation exposure. OBJECTIVE: To examine the relationship between body mass index (BMI) and fluoroscopy time and radiation dose during intra-articular hip injections. DESIGN: Retrospective study. SETTING: The study was conducted at an academic orthopedic center. All procedures were performed by physicians board-certified in PM&R and/or with subspecialty certification in sports medicine, or by a trainee under close supervision from an attending physician. PARTICIPANTS: All patients who underwent fluoroscopically guided intra-articular hip injections between the years 2003-2014 with a documented height/weight, fluoroscopy time, and radiation dose. INTERVENTIONS: All patients received unilateral or bilateral intra articular hip injections with fluoroscopic guidance. Fluoroscopy time and dose were recorded. MAIN OUTCOME MEASURES: The main outcome measures were fluoroscopy time and radiation dose. A Bonferroni correction was implemented for multiple comparisons, defining statistical significance at P < .01. RESULTS: A total of 438 subjects (446 injections) were included. Mean fluoroscopy times were 17.4 +/- 9.9, 17.5 +/- 11.4, and 19.1 +/- 13.4 seconds for normal, overweight, and obese body mass (BMI) index groups, respectively, with no significant difference between groups (P = .148). The mean radiation doses were 601 +/- 690, 678 +/- 558, and 1049 +/- 812 mGy-cm(2), respectively (P < .001, r = 0.29). There was no association of age (P = .03), needle length (P = .34) or trainee involvement (P = .159) with fluoroscopy time. CONCLUSION: This study demonstrates that increasing BMI leads to elevated radiation dose during fluoroscopically guided intra articular hip injections. The increased radiation experienced by patients with a larger BMI, however, is likely negligible. PMID- 26826619 TI - Characterization of tip size and geometry of the pipettes used in scanning ion conductance microscopy. AB - Scanning ion-conductance microscopy (SICM) belongs to the family of scanning probe microscopies. The spatial resolution of these techniques is limited by the size of the probe. In SICM the probe is a pipette, obtained by heating and pulling a glass capillary tubing. The size of the pipette tip is therefore an important parameter in SICM experiments. However, the characterization of the tip is not a consolidated routine in SICM experimental practice. In addition, potential and limitations of the different methods available for this characterization may not be known to all users. We present an overview of different methods for characterizing size and geometry of the pipette tip, with the aim of collecting and facilitating the use of several pieces of information appeared in the literature in a wide interval of time under different disciplines. In fact, several methods that have been developed for pipettes used in cell physiology can be also fruitfully employed in the characterization of the SICM probes. The overview includes imaging techniques, such as scanning electron microscopy and atomic Force microscopy, and indirect methods, which measure some physical parameter related to the size of the pipette. Examples of these parameters are the electrical resistance of the pipette filled with a saline solution and the surface tension at the pipette tip. We discuss advantages and drawbacks of the methods, which may be helpful in answering a wide range of experimental questions. PMID- 26826620 TI - The neurobiology of MMN and implications for schizophrenia. AB - Although the scientific community appears to know a lot about MMN, about its neural generators and the computational processes that underlie its generation, do we have sufficient knowledge to understand what causes the reduction of MMN amplitude in schizophrenia? Here we attempt to integrate the evidence presented in this series of papers for the special issue on MMN in schizophrenia together with evidence from other new relevant research and ask--what have we learnt? While MMN research was the purview for decades of psychophysiologists interested in event-related potentials derived from scalp recorded EEG, it is now part of mainstream neuroscience research attracting the interest of basic auditory neuroscientists, neurobiologists and computational modellers. The confluence of these developments together with increasing clinical research has certainly advanced our understanding of the causes of reduced MMN in schizophrenia as this integrative review attempts to demonstrate--but much remains to be learnt. Future advances will rely on the application of multiple methodologies and approaches in order to arrive at better understanding of the neurobiology of MMN and implications for schizophrenia. PMID- 26826618 TI - Direct hydrogel encapsulation of pluripotent stem cells enables ontomimetic differentiation and growth of engineered human heart tissues. AB - Human engineered heart tissues have potential to revolutionize cardiac development research, drug-testing, and treatment of heart disease; however, implementation is limited by the need to use pre-differentiated cardiomyocytes (CMs). Here we show that by providing a 3D poly(ethylene glycol)-fibrinogen hydrogel microenvironment, we can directly differentiate human pluripotent stem cells (hPSCs) into contracting heart tissues. Our straight-forward, ontomimetic approach, imitating the process of development, requires only a single cell handling step, provides reproducible results for a range of tested geometries and size scales, and overcomes inherent limitations in cell maintenance and maturation, while achieving high yields of CMs with developmentally appropriate temporal changes in gene expression. We demonstrate that hPSCs encapsulated within this biomimetic 3D hydrogel microenvironment develop into functional cardiac tissues composed of self-aligned CMs with evidence of ultrastructural maturation, mimicking heart development, and enabling investigation of disease mechanisms and screening of compounds on developing human heart tissue. PMID- 26826621 TI - 3D morphometric analysis of the human incudomallear complex using clinical cone beam CT. AB - Human middle ears show large morphological variations. This could affect our perception of hearing and explain large variation in experimentally obtained transfer functions. Most morphological studies focus on capturing variation by using landmarks on cadaveric temporal bones. We present statistical shape analysis based on clinical cone beam CT (CBCT) scans of 100 patients. This allowed us to include surface information on the incudomallear (IM) complex (joint, ligaments and tendon not included) of 123 healthy ears with a scanning resolution of 150 MUm and without a priori assumptions. Statistical shape modeling yields an average geometry for the IM complex and the variations present in the population with a high precision. Mean values, variation and correlations among anatomical features (length of manubrium, combined length of malleus head and neck, lengths of incus long and short process, enclosing angles, ossicular lever ratio, incudomallear angle, and principal moments of inertia) are reported and compared to results from the literature. Most variation is found in overall size and the angle between incus and malleus. The compact representation provided by statistical shape modeling is demonstrated and its benefits for surface modeling are discussed. PMID- 26826623 TI - Answer to the letter regarding "Valve surgery in active infective endocarditis: A simple score to predict in-hospital prognosis". PMID- 26826622 TI - Three-year follow-up outcomes of SES and PES in a randomized controlled study stratified by the presence of diabetes mellitus: J-DEsSERT trial. AB - BACKGROUND: Three-year clinical follow-up of patients with diabetes mellitus (DM) in the Japan-Drug Eluting Stents Evaluation; a Randomized Trial (J-DESsERT) using 2 different drug eluting stents (DES). A recent study demonstrated that efficacy of sirolimus eluting stents (SES) attenuated over time in diabetic patients. METHODS: In the largest trial of its kind, 1724 DM patients out of 3533 enrolled patients were randomized to either SES or paclitaxel eluting stents (PES). RESULTS: There were no significant differences in baseline clinical characteristics aside from hypertension. Incidence of major adverse cardiac cerebrovascular events (MACCE) mainly due to higher target vessel failure (TVF) initially indicated a benefit in SES (MACCE rate at 1 year: SES 9.4%, PES 12.2%, p=0.08); however this had attenuated by the time of the 3-year follow-up (MACCE rate from 1 to 3 years: SES 8.4%, PES 6.1%, p=0.10). A similar pattern was observed in insulin-treated patients: MACCE rate from 1 to 3 years was 10.5% in SES and 6.4% in PES (p=0.25). Angiographic follow-up also resulted in higher major adverse cardiac event (MACE) rates at 1 year (presence 11.5%, absence 8.3%, p=0.04); however by 3 years rates were similar regardless of the presence of angiographic follow-up (MACE rate at 3 years: presence 16.0%, absence 14.5%, p=0.35). CONCLUSIONS: The superiority of SES over PES in MACCE at 1 year had attenuated by 3-year follow-up. Eventually, the 3-year safety and efficacy profiles were similar regardless of insulin treatment. PMID- 26826624 TI - Thrombelastography detects dabigatran at therapeutic concentrations in vitro to the same extent as gold-standard tests. AB - BACKGROUND/OBJECTIVES: Dabigatran is an oral anticoagulant approved for treatment of non-valvular atrial fibrillation, deep venous thrombosis (DVT), pulmonary embolism and prevention of DVT following orthopedic surgery. Monitoring of the dabigatran level is essential in trauma and bleeding patients but the available plasma-based assays may not sufficiently display its hemostatic effect. This study investigated the in vitro effect of different concentrations of dabigatran on whole blood thrombelastography (TEG) and its correlation to the specific but time-consuming plasma-based tests Hemoclot and Ecarin Clotting Time (ECT). METHOD: Blood was collected from 8 healthy donors (two females, six males) with a median age of 46 years and it was spiked with dabigatran to a range of plasma concentrations (0, 50, 100, 200 and 400 ng/ml) covering the therapeutic level. RESULTS: Mean TEG R at 0 ng/ml=5.963 min, 50 ng/ml=7.425 min, 100 ng/ml=8.425 min, 200 ng/ml=9.775 min, 400 ng/ml=11.813 min. A significant overall increase (p=0.001) in TEG reaction time (R) was found across increasing dabigatran concentrations i.e. 0 vs 50 vs 100 vs 200 vs 400 ng/ml (p<0.000 p=0.027 p=0.026, p=0.005, respectively). TEG R correlated strongly with Hemoclot (R(2)=0.891, p<0000) and ECT (R(2)=0.914, p<0.000) and Hemoclot and ECT were strongly inter correlated (R(2)=0.978, p<0.000). CONCLUSION: The whole blood viscoelastic assay TEG R displayed linearity towards fixed concentrations of dabigatran and correlated strongly to the current gold-standard tests Hemoclot and ECT, for assessing dabigatran. TEG R is applicable as a rapid and precise whole blood monitoring test for dabigatran treated patients in the emergency setting. PMID- 26826625 TI - Trends in incidence and prevalence of hospitalization for atrial fibrillation and associated mortality in Western Australia, 1995-2010. AB - OBJECTIVE: Hospitalization for atrial fibrillation (AF) is a large and growing public health problem. We examined current trends in the incidence, prevalence, and associated mortality of first-ever hospitalization for AF. METHODS: Linked hospital admission data were used to identify all Western Australia residents aged 35-84 years with prevalent AF and incident (first-ever) hospitalization for AF as a principal or secondary diagnosis during 1995-2010. RESULTS: There were 57,552 incident hospitalizations, mean age 69.8 years, with 41.4% women. Over the calendar periods, age- and sex-standardized incidence of hospitalization for AF as any diagnosis declined annually by 1.1% (95% CI; 0.93, 1.29), while incident AF as a principal diagnosis increased annually by 1.2% (95% CI; 0.84, 1.50). Incident AF hospitalization was higher among men than women, and 15-fold higher in the 75-84 compared with 35-64 year age group. The age- and sex-standardized prevalence of AF increased annually by 2.0% (95% CI; 1.88, 2.03) over the same period. Comorbidity trends were mixed with diabetes and valvular heart disease increasing, and hypertension, coronary artery disease, heart failure, cerebrovascular disease, and chronic kidney disease decreasing. The 1-year all cause mortality after incident AF hospitalization declined from 17.6% to 14.6% (trend P<0.001), with an adjusted hazard ratio of 0.86 (95% CI; 0.81, 0.91). CONCLUSION: This contemporary study shows that incident AF hospitalization is not increasing except for AF as a principal diagnosis, while population prevalence of hospitalized AF has risen substantially. The high 1-year mortality following incident AF hospitalization has improved only modestly over the recent period. PMID- 26826626 TI - Implantation of a single coil ICD via persistent left superior vena cava. PMID- 26826627 TI - Effect of oversizing and elliptical shape of aortic annulus on transcatheter valve hemodynamics: An in vitro study. AB - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is often performed in patients with non-circular aortic annulus and in oversizing (OS) conditions. The impact of elliptical annulus shape and the consequences of oversizing/underdeployment on the hemodynamic performance are still debated. OBJECTIVE: This in-vitro study aims to assess and compare the valve hemodynamic performances of the Edwards SAPIEN transcatheter heart valve (THV) in the different current conditions of use: important oversizing in small circular annuli and in elliptical annuli, moderate oversizing in circular and in elliptical annuli of various degrees of eccentricity. METHODS: A pulsed cardiovascular simulator was used. Edwards SAPIEN 23 and 26 (mm) were implanted in different circular and elliptical annuli of various sizes and eccentricity. Transvalvular mean pressure gradients (TPGm), effective orifice area (EOA) after implantation of Edwards SAPIEN THV were measured by Doppler-echocardiography and the performance index (PI=100 * EOA/Annulus Area) was calculated. Para and transvalvular regurgitation was assessed by color-Doppler and leakage volume was quantified by flowmeter measurement. RESULTS: For a given aortic annulus area, EOAs after implantation of Edwards SAPIEN THV were generally larger and TPGms lower with elliptical annuli compared to circular annuli. The PI was higher (p=0.047) for elliptical (48 +/- 3%) than for circular annuli (43 +/- 5%). Paravalvular regurgitation occurred only in the case of the SAPIEN 26 implanted in the elliptical annulus with highest eccentricity. CONCLUSION: The results of this in-vitro study suggest that the EOAs of Edwards SAPIEN are better in elliptical than in circular annuli. No transvalvular regurgitation occurred and only one paravalvular regurgitation was observed after implantation of SAPIEN 26 in the highly eccentric annulus. PMID- 26826628 TI - Reports of perceptual distortion of the face are common in patients with different types of chronic oro-facial pain. AB - Anecdotally, chronic oro-facial pain patients may perceive the painful face area as 'swollen'. Because there are no clinical signs, these self-reported 'illusions' may represent perceptual distortions and can be speculated to contribute to the maintenance of oro-facial pain. This descriptive study investigated whether chronic oro-facial pain patients experience perceptual distortions - a kind of body image disruption. Sixty patients were consecutively recruited to fill in questionnaires regarding i) pain experience, ii) self reports of perceptual distortion and iii) psychological condition. Perceptual distortions were examined in the total group and in three diagnostic subgroups: i) painful post-traumatic trigeminal neuropathy (PPTN), ii) painful temporomandibular disorder (TMD) or iii) persistent idiopathic facial pain (PIFP). A large proportion of oro-facial pain patients reported perceptual distortions of the face (55.0%). In the diagnostic subgroups, perceptual distortions were most pronounced in PPTN patients (81.5%) but with no significant group differences. In the total group of chronic oro-facial pain patients, the present pain intensity explained 16.9% of the variance in magnitude of the perceptual distortions (R(2) = 16.9, F(31) = 6.3, P = 0.017). This study demonstrates that many chronic oro-facial pain patients may experience perceptual distortions. Future studies may clarify the mechanisms underlying perceptual distortions, which may point towards new complementary strategies for the management of chronic oro-facial pain. PMID- 26826629 TI - Randomized trial of a multidisciplinary lifestyle intervention in HIV-infected patients with moderate-high cardiovascular risk. AB - OBJECTIVE: To assess the impact of a multidisciplinary lifestyle intervention on cardiovascular risk and carotid intima-media thickness (c-IMT) in HIV-infected patients with Framingham scores (FS) > 10%. DESIGN: Randomized pilot study; follow-up 36 months. METHODS: Virologically suppressed adult HIV-1-infected patients with FS >10% were randomized 1:1 to the intervention group (multidisciplinary lifestyle intervention) or control group (routine care). At baseline and months 12, 24 and 36, lipid parameters were analyzed and carotid ultrasound was performed to determine c-IMT and presence of plaques. Biomarkers were measured at baseline and month 36. The primary endpoints were lipid and FS changes at 36 months. RESULTS: Fifty-four patients were included, 27 in each arm. Median age was 50.5 years, all patients but one were men, and FS was 16.5%. Relative to controls, total and LDL cholesterol had significantly decreased in the intervention group at 24 months (p = 0.039, p = 0.011, respectively). However, no differences between groups were found at month 36 in lipid variables, neither in FS. Tobacco use decreased in the intervention group (p = 0.031). At baseline, 74.5% of patients had subclinical atherosclerosis, and at month 36, we observed a progression in c-IMT that was greater in the intervention group (p = 0.030). D-dimer increased (p = 0.027) and soluble intercellular adhesion molecule 1 decreased (p = 0.018) at 36 months. CONCLUSIONS: In this cohort of HIV-infected patients with FS>10% and a high percentage of subclinical atherosclerosis, a multidisciplinary lifestyle intervention resulted in a slight improvement in some cardiovascular risk factors and the FS during the first 2 years, but did not prevent c-IMT progression. PMID- 26826630 TI - Musculoskeletal overuse injuries and heart rate variability: Is there a link? AB - Accurate detection and prevention of overuse musculoskeletal injuries is limited by the nature of somatic tissue injury. In the pathogenesis of overuse injuries, it is well recognized that an abnormal inflammatory response occurs within somatic tissue before pain is perceived which can disrupt the normal remodeling process and lead to subsequent degeneration. Current overuse injury prevention methods focused on biomechanical faults or performance standards lack the sensitivity needed to identify the status of tissue injury or repair. Recent evidence has revealed an apparent increase in the prevalence and impact of overuse musculoskeletal injuries in athletics. When compared to acute injuries, overuse injuries have a potentially greater negative impact on athletes' overall health burden. Further, return to sport rehabilitation following overuse injury is complicated by the fact that the absence of pain does not equate to complete physiological healing of the injured tissue. Together, this highlights the need for exercise monitoring and injury prevention methods which incorporate assessment of somatic tissue response to loading. One system primarily involved in the activation of pathways and neuromediators responsible for somatic tissue repair is the autonomic nervous system (ANS). Although not completely understood, emerging research supports the critical importance of peripheral ANS activity in the health and repair of somatic tissue injury. Due to its significant contributions to cardiac function, ANS activity can be measured indirectly with heart rate monitoring. Heart rate variability (HRV) is one index of ANS activity that has been used to investigate the relationship between athletes' physiological response to accumulating training load. Research findings indicated that HRV may provide a reflection of ANS homeostasis, or the body's stress recovery status. This noninvasive marker of the body's primary driver of recovery has the potential to incorporate important and as yet unmonitored physiological mechanisms involved in overuse injury development. We hypothesize that abnormal somatic tissue response to accumulating microtrauma may modulate ANS activity at the level of HRV. Exploring the link between HRV modulation and somatic tissue injury has the potential to reveal the putative role of ANS homeostasis on overuse musculoskeletal injury development. PMID- 26826631 TI - Arterial Tortuosity Syndrome reveals function of dehydroascorbic acid in collagen and elastin synthesis: Implications for skin care. AB - Some investigations in Arterial Tortuosity Syndrome (ATS) suggest that impaired intracellular transport of the oxidized form of vitamin C (dehydroascorbic acid, DHAA) is at the core of the pathogenesis. Lack of vitamin C for lysyl- and prolyl hydroxylase activity may explain the defects in collagen and elastin formation found in ATS, and draws strong parallels between ATS and scurvy. Topically applied vitamin C has a well-established basis in the field of skin care, and part of its benefit is attributed to proper collagen formation in the skin. The ATS studies suggest that DHAA transport is necessary for normal skin collagen formation, and this has implications as to the forms of vitamin C best-suited for topical skin care. PMID- 26826632 TI - Completion to the article "Cancer as a carcinogenic hyper-cycle and a RNA world progress" (Medical Hypotheses 81 (2013) 288-292). PMID- 26826633 TI - Drug-induced long QT syndrome increases the risk of drowning. AB - There is strong evidence linking inherited long QT syndromes with an increased risk of drowning due to fatal arrhythmias in the water. Drug-induced long QT syndrome (DILQTS) is hypothesized to increase the risk of drowning by similar mechanisms. It is suggested that QT prolongation caused by a drug or drugs, when combined with the autonomic conflict associated with the mammalian dive reflex and/or the cold shock reflex, sets up conditions that may result in a sudden fatal arrhythmia while in water - thus an increased risk of drowning related to a drug-induced prolongation of the QT interval. Many widely used drugs prolong the QT interval thus raising a drug safety issue that needs confirmation or refutation. PMID- 26826634 TI - Circuits regulating pleasure and happiness in major depression. AB - The introduction of selective serotonin reuptake inhibitors has gradually changed the borders of the major depression disease class. Anhedonia was considered a cardinal symptom of endogenous depression, but the potential of selective serotonin reuptake inhibitors to treat anxiety disorders has increased the relevance of stress-induced morbidity. This shift has led to an important heterogeneity of current major depressive disorder. The complexity can be disentangled by postulating the existence of two different but mutually interacting neuronal circuits regulating the intensity of anhedonia (lack of pleasure) and dysphoria (lack of happiness). These circuits are functionally dominated by partly closed limbic (regulating misery-fleeing behaviour) and extrapyramidal (regulating reward-seeking behaviour) cortico-striato-thalamo cortical (CSTC) circuits. The re-entry circuits include the shell and core parts of the accumbens nucleus, respectively. Pleasure can be considered to result from finding relief from the hypermotivation to exhibit rewarding behaviour, and happiness from finding relief from negative or conflicting circumstances. Hyperactivity of the extrapyramidal CSTC circuit results in craving, whereas hyperactivity of the limbic system results in dysphoria. PMID- 26826635 TI - Immediate hemodynamic changes after revascularization of complete infrarenal aortic occlusion: A classic issue revisited. AB - Chronic total occlusion of the infrarenal aorta (CTOA) is a rare disease, characterized by severe impairment of limb perfusion. It is advocated that revascularization may improve survival rates, presumably due to improved cardiovascular performance; however no experimental or clinical data exist to identify a clear causative correlation and provide a relevant pathophysiologic background. Therefore we conducted a pilot study based on pulse wave analysis to detect the hemodynamic changes immediately after revascularization, in a group of six consecutive patients with CTOA. All patients were subjected to non-invasive measurements 1 day before surgery and at the end of the 1st postoperative month. Pulse wave analysis was performed noninvasively with a novel validated brachial cuff-based automatic oscillometric device. All patients had markedly preoperative high Augmentation Index (adjusted at heart rate 75 beats/min, AI@75). The AI@75 decreased from 46 +/- 6.6 preoperatively to 24 +/- 5.7 (p 0.0002). Wave reflection magnitude decreased from 72.3 +/- 5.2% to 63 +/- 6.7% (p 0.02). Cardiax index increased from 2.8 +/- 1.2 to 3.4 +/- 1.2l/min * 1/m(2) (p 0.41). Pulse wave velocity remained practically unchanged post-interventionally. These findings show that central aorta hemodynamics can be improved immediately following revascularization procedures in patients with complete occlusion of the entire length of the infrarenal aorta and can constitute the background of improved postoperative life-expectancy. PMID- 26826636 TI - An empty uterine cavity in the puerperium is associated with no further preeclampsia-eclampsia episodes. PMID- 26826637 TI - Personalized development of human organs using 3D printing technology. AB - 3D printing is a technique of fabricating physical models from a 3D volumetric digital image. The image is sliced and printed using a specific material into thin layers, and successive layering of the material produces a 3D model. It has already been used for printing surgical models for preoperative planning and in constructing personalized prostheses for patients. The ultimate goal is to achieve the development of functional human organs and tissues, to overcome limitations of organ transplantation created by the lack of organ donors and life long immunosuppression. We hypothesized a precision medicine approach to human organ fabrication using 3D printed technology, in which the digital volumetric data would be collected by imaging of a patient, i.e. CT or MRI images followed by mathematical modeling to create a digital 3D image. Then a suitable biocompatible material, with an optimal resolution for cells seeding and maintenance of cell viability during the printing process, would be printed with a compatible printer type and finally implanted into the patient. Life-saving operations with 3D printed implants were already performed in patients. However, several issues need to be addressed before translational application of 3D printing into clinical medicine. These are vascularization, innervation, and financial cost of 3D printing and safety of biomaterials used for the construct. PMID- 26826638 TI - Myeloid-derived suppressor cells (MDSC) facilitate distant metastasis of malignancies by shielding circulating tumor cells (CTC) from immune surveillance. AB - The mechanisms of distant metastasis of malignancies largely remain unknown. Circulating tumor cells (CTC) derived from the primary cancer initiate distant metastasis by entering and traversing the bloodstream. Current methods to detect CTC are based on the notion that CTC do not express the common leukocyte antigen CD45. However, these methods neglect the fact that CTC can directly adhere to platelets and immune cells and therefore appear to be CD45-positive. The potential effects of interactions between CTC and adhesive immune cells have been largely overlooked, despite the fact that most CTC are killed by immune effector cells and only those that evade immune surveillance result in clonal expansion and metastatic lesions. It is crucial to define the characteristics that allow a select CTC population to escape immune surveillance; particularly, it must be determined whether interactions between CTC and adhesive immune cells provide a protective effect on CTC survival. If interactions between CTC and adhesive immune cells offer a selective advantage to those CTC cells, the next consideration is which characteristics of a CTC-immune cell population allow sufficient protection to facilitate immune evasion. Myeloid-derived suppressor cells (MDSC) are a large heterogeneous population of immature myeloid cells that accumulate during cancer progression to induce extensively systemic and local immunosuppression, a phenomenon that has been demonstrated to facilitate cancer distant metastasis. We hypothesize, therefore, that CTC populations interacting with adhesive immune cells will have different biological behavior than CTC populations alone. Further, we hypothesize that CTC can create a defensive shield consisting of adhesive MDSC, which allows evasion of immune surveillance and therefore facilitates distant metastatic lesions. This possibility highlights the importance of direct interactions between CTC and adhesive immune cells and suggests the potential target that the CTC-MDSC cluster represents for prevention and treatment of distant metastasis of malignancies. PMID- 26826639 TI - Microbes, molecular mimicry and molecules of mood and motivation. AB - The hypothesis proposed is that functional disorders, such as irritable bowel syndrome, chronic fatigue syndrome and anorexia nervosa are caused by auto antibodies to neuronal proteins induced by molecular mimicry with microbial antigens. The age incidence of these conditions, the marked female excess, increase with economic and technological advance, precipitation by infection, and the paucity of histological changes are all consistent with the hypothesis. It can be tested directly using human sera to search for cross reaction with brain proteins in model systems such as Drosophila melanogaster. The conditions might be amenable to treatment using pooled immunoglobulin. Identification and elimination from the microbial flora of the bacteria that express the cross reacting antigens should be possible. PMID- 26826640 TI - Does the ADMA/DDAH/NO pathway modulate early regression of left ventricular hypertrophy with esmolol? AB - Hypertensive left ventricular hypertrophy (LVH) is a maladaptive response to chronic pressure overload and a strong independent risk factor for cardiovascular disease. Regression of LVH is associated with improved prognosis. Regression of LVH with antihypertensive therapy (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, and diuretics) has been reported, although only after long-term treatment. Asymmetrical dimethylarginine (ADMA), the most potent endogenous NO synthase inhibitor, is emerging as an important cardiovascular risk factor in patients with arterial hypertension and LVH, and dimethylarginine dimethylaminohydrolase (DDAH) is the mechanism that most frequently leads to accumulation of ADMA (plasma ADMA is cleared in small part by renal excretion, although the bulk of ADMA is degraded by DDAH). Left ventricular mass is strongly modulated by the NO system. As an important inhibitor of the bioavailability of NO, ADMA is an underlying mechanism of LVH. Beta-blockers can induce regression of LVH and reduced plasma ADMA levels. Oxidative stress is increased in patients with LVH, and this in turn increases generation of ADMA. In a previous preclinical study of spontaneously hypertensive rats, we found that short-term treatment (48 h) with esmolol reverses early LVH, increases the bioavailability of NO, and improves antioxidant status in plasma. Therefore, we propose that the ADMA/DDAH/NO pathway could modulate early regression of LVH with esmolol. PMID- 26826641 TI - Constructing the ecstasy of MDMA from its component mental organs: Proposing the primer/probe method. AB - The drug MDMA, commonly known as ecstasy, produces a specific and distinct open hearted mental state, which led to the creation of a new pharmacological class, "entactogens". Extensive literature on its mechanisms of action has come to characterize MDMA as a "messy" drug with multiple mechanisms, but the consensus is that the distinctive entactogenic effects arise from the release of neurotransmitters, primarily serotonin. I propose an alternative hypothesis: The entactogenic mental state is due to the simultaneous direct activation of imidazoline-1 (I1) and serotonin-2 (5-HT2) receptors by MDMA. This hypothesis emerges from "mental organ" theory, which embodies many hypotheses, the most relevant of which are: "Mental organs" are populations of neurons that all express their defining metabotropic receptor, and each mental organ plays a distinct role in the mind, a role shaped by evolution as mental organs evolve by duplication and divergence. Mental organs are the mechanism by which evolution sculpts the mind. Mental organs can be in or out of consciousness. In order for a mental organ to enter consciousness, three things must happen: The mental organ must be activated directly at its defining receptor. 5-HT2 must be simultaneously activated. One of the functions of activated 5-HT2 is to load other simultaneously activated mental organs fully into consciousness. In some cases THC must be introduced to remove long-term blocks mediated by the cannabinoid system. I propose the "primer/probe" method to test these hypotheses. A "primer" is a drug that selectively activates 5-HT2 (e.g. DOB or MEM) or serotonin-1 (5 HT1) and 5-HT2 (e.g. DOET or 2C-B-fly). A "probe" is a drug that activates a receptor whose corresponding mental organ we wish to load into consciousness in order to understand its role in the mind. The mental organ is loaded into consciousness when the primer and probe are taken together, but not when taken separately. For example, the blood pressure medications rilmenidine and moxonidine are selective for imidazoline-1 and can be used to test the hypothesis that the entactogenic mental effects of MDMA are due to loading the imidazoline-1 mental organ into consciousness. The primer/probe method is not limited to testing the specific hypothesis about MDMA and imidazoline, but is a general method for studying the role of mental organs in the mind. For example, the role of dopamine mental organs can be studied by using Parkinson's drugs such as ropinirole or pramipexole as probes. PMID- 26826642 TI - How delusion is formed? AB - Traditionally, delusions have been considered to be the products of misinterpretation and irrationality. However, some theorists have argued that delusions are normal or rational cognitive responses to abnormal experiences. That is, when a recently experienced peculiar event is more plausibly explained by an extraordinary hypothesis, confidence in the veracity of this extraordinary explanation is reinforced. As the number of such experiences, driven by the primary disease process in the perceptual domain, increases, this confidence builds and solidifies, forming a delusion. We tried to understand the formation of delusions using a simulation based on Bayesian inference. We found that (1) even if a delusional explanation is only marginally more plausible than a non delusional one, the repetition of the same experience results in a firm belief in the delusion. (2) The same process explains the systematization of delusions. (3) If the perceived plausibility of the explanation is not consistent but varies over time, the development of a delusion is delayed. Additionally, this model may explain why delusions are not corrected by persuasion or rational explanation. This Bayesian inference perspective can be considered a way to understand delusions in terms of rational human heuristics. However, such experiences of "rationality" can lead to irrational conclusions, depending on the characteristics of the subject. PMID- 26826643 TI - Cytotoxic T lymphocytes as a potential brake of keratinocyte proliferation in psoriasis. AB - Psoriasis is a chronic papulosquamous skin disease, histologically characterized by epidermal hyperproliferation and dermal infiltration of inflammatory cells. The majority of T lymphocytes infiltrating dermis are CD4+ T lymphocytes secreting type 1 and type 17 cytokines. These cytokines are responsible for triggering keratinocyte proliferation as well as chemokine secretion and subsequent migration of other inflammatory cells in the skin. Contrarily, lymphocytes that accumulate in epidermis are mainly CD8+ T lymphocytes. According to the recent findings, these cells can also secrete type 1 and type 17 cytokines. However, it is demonstrated so far that epidermal CD8+ T lymphocytes contain higher amounts of cytolytic molecules, such as perforin, granzyme B and granulysin whose role in psoriasis pathogenesis is still unknown. Therefore, in this article we hypothesize the active involvement of cell mediated cytotoxicity in killing the proliferating keratinocytes as a mechanism of potential self defense and possible brake in psoriatic plaque formation, maintaining skin homeostasis. PMID- 26826646 TI - Impact of water quality on chlorine demand of corroding copper. AB - Copper is widely used in drinking water premise plumbing system materials. In buildings such as hospitals, large and complicated plumbing networks make it difficult to maintain good water quality. Sustaining safe disinfectant residuals throughout a building to protect against waterborne pathogens such as Legionella is particularly challenging since copper and other reactive distribution system materials can exert considerable demands. The objective of this work was to evaluate the impact of pH and orthophosphate on the consumption of free chlorine associated with corroding copper pipes over time. A copper test-loop pilot system was used to control test conditions and systematically meet the study objectives. Chlorine consumption trends attributed to abiotic reactions with copper over time were different for each pH condition tested, and the total amount of chlorine consumed over the test runs increased with increasing pH. Orthophosphate eliminated chlorine consumption trends with elapsed time (i.e., chlorine demand was consistent across entire test runs). Orthophosphate also greatly reduced the total amount of chlorine consumed over the test runs. Interestingly, the total amount of chlorine consumed and the consumption rate were not pH dependent when orthophosphate was present. The findings reflect the complex and competing reactions at the copper pipe wall including corrosion, oxidation of Cu(I) minerals and ions, and possible oxidation of Cu(II) minerals, and the change in chlorine species all as a function of pH. The work has practical applications for maintaining chlorine residuals in premise plumbing drinking water systems including large buildings such as hospitals. PMID- 26826645 TI - Sorption of testosterone on partially-dispersed soil particles of different size fractions: Methodology and implications. AB - Sorption of hormones to soil particles of different size fractions (DSFs) has been studied to understand their fate and transport (F/T) in soils. Conventional studies fractionated the soil particles into DSFs by using the high speed stirring method and/or adding surfactants to fully disperse the bulk soil. However, the natural processes (e.g., soil erosion, irrigation) often are relatively mild, and many soil particles may be still in the aggregate form. In this study, a method was developed for conducting the sorption test of a representative hormone (i.e., testosterone) to bulk soils first and then analyzing the results against DSFs. Results indicated the particle size distribution (PSD) of the two representative soils tested with partially dispersed and fully-dispersed methods was significantly different due to the attachment of clay particles on sand and silt. Testosterone was sorbed mainly by the dominant aggregates even though they might have relatively lower sorption affinity than that of clays. However, the small particles (<2000 nm), even with ~5% mass of the bulk soil, contributed more than 30% of sorbed testosterone in the "whole" soils. The partially-dispersed soil particles of DSFs should be used to understand the transport of hormone in runoff, because using the fully dispersed soil particles will overestimate while the whole soil method will underestimate the transport potential. With the methodology developed in this study, the sorption tests will not compromise soil's original properties (e.g., aggregates) or the competition (e.g., sorption) among soil particles, and the contribution of DSFs (particularly the partially-dispersed aggregates) to the sorption of the "whole" soil can be determined. PMID- 26826644 TI - Submolecular regulation of cell transformation by deuterium depleting water exchange reactions in the tricarboxylic acid substrate cycle. AB - The naturally occurring isotope of hydrogen ((1)H), deuterium ((2)H), could have an important biological role. Deuterium depleted water delays tumor progression in mice, dogs, cats and humans. Hydratase enzymes of the tricarboxylic acid (TCA) cycle control cell growth and deplete deuterium from redox cofactors, fatty acids and DNA, which undergo hydride ion and hydrogen atom transfer reactions. A model is proposed that emphasizes the terminal complex of mitochondrial electron transport chain reducing molecular oxygen to deuterium depleted water (DDW); this affects gluconeogenesis as well as fatty acid oxidation. In the former, the DDW is thought to diminish the deuteration of sugar-phosphates in the DNA backbone, helping to preserve stability of hydrogen bond networks, possibly protecting against aneuploidy and resisting strand breaks, occurring upon exposure to radiation and certain anticancer chemotherapeutics. DDW is proposed here to link cancer prevention and treatment using natural ketogenic diets, low deuterium drinking water, as well as DDW production as the mitochondrial downstream mechanism of targeted anti-cancer drugs such as Avastin and Glivec. The role of (2)H in biology is a potential missing link to the elusive cancer puzzle seemingly correlated with cancer epidemiology in western populations as a result of excessive (2)H loading from processed carbohydrate intake in place of natural fat consumption. PMID- 26826647 TI - Relationships of cognitive load on eating and weight-related behaviors of young adults. AB - Little is known about the relationship between weight-related behaviors and cognitive load (working memory available to complete mental activities like those required for planning meals, selecting foods, and other health-related decisions). Thus, the purpose of this study was to explore associations between cognitive load and eating behaviors, physical activity, body mass index (BMI), and waist circumference of college students. College students (n=1018) from 13 institutions completed an online survey assessing eating behaviors (e.g., routine and compensatory restraint, emotional eating, and fruit/vegetable intake), stress level, and physical activity level. BMI and waist circumference were measured by trained researchers. A cognitive load score was derived from stress level, time pressure/income needs, race and nationality. High cognitive load participants (n=425) were significantly (P<0.05) more likely to be female, older, and further along in school than those with low cognitive loads (n=593). Compared to low cognitive load participants, high cognitive load participants were significantly more likely to eat <5 cups of fruits/vegetables/day, have greater routine and compensatory restraint, and greater susceptibility to eating in response to external cues and emotional eating. Both males and females with high cognitive load scores had a non-significant trend toward higher BMIs, waist circumferences, and drinking more alcohol than low cognitive load counterparts. In conclusion, cognitive load may be an important contributor to health behaviors. Understanding how cognitive load may affect eating and other weight-related behaviors could potentially lead to improvements in the effectiveness of obesity prevention and intervention programs. PMID- 26826648 TI - Palatable Eating Motives Scale in a college population: Distribution of scores and scores associated with greater BMI and binge-eating. AB - The main goal of this study was to provide distributive data for the Palatable Eating Motives Scale (PEMS) on a large (N=1947) ethnically-diverse college student population along with motive scores characteristic of obesity and binge eating severity. Students completed the PEMS, or a revised version of the PEMS, the Binge Eating Scale, and reported height and weight for a body mass index (BMI). The PEMS identified Coping, Reward Enhancement, Social, and Conformity motives for eating tasty but unhealthy foods for reasons other than hunger. The revised PEMS (included here) had better goodness-of-fit with the motives. Percentile rankings are presented for each of the motive scores. Separate Coping scores are presented for females and males given a modest effect size for females to score higher. Generally, scores on Coping, Reward Enhancement, Conformity, and a total PEMS score in the 70th percentile (those scoring higher than 70% of the sample) were associated with obesity and severe binge-eating. Unlike these motives, Social scores were the highest at each percentile rank but unassociated with BMI or binge-eating, reflecting the culturally-normative intake of these foods for social reasons. These distribution scores on PEMS motives in college students along with scores linked to higher BMI and binge-eating severity represent the first reported data of this type. Knowledge of these scores can be used to individualize and correspondingly improve current strategies aimed at preventing and treating obesity, binge-eating, maladaptive use of food to regulate internal and external pressures, and to improve overall nutritional health. PMID- 26826649 TI - Youth internalizing symptoms, sleep-related problems, and disordered eating attitudes and behaviors: A moderated mediation analysis. AB - PURPOSE: Internalizing symptoms increase the risk for disordered eating; however, the mechanism through which this relationship occurs remains unclear. Sleep related problems may be a potential link as they are associated with both emotional functioning and disordered eating. The present study aims to evaluate the mediating roles of two sleep-related problems (sleep disturbance and daytime sleepiness) in the relationship between youth internalizing symptoms and disordered eating, and to explore if age moderates these relations. METHODS: Participants were 225 youth (8-17years) attending a primary care appointment. Youth and legal guardians completed questionnaires about youth disordered eating attitudes and behaviors, internalizing symptoms, sleep disturbance, and daytime sleepiness. Mediation and moderated mediation analyses were utilized. RESULTS: The mediation model revealed both youth sleep disturbance and daytime sleepiness independently mediated the association between internalizing symptoms and disordered eating attitudes and behaviors, and explained 18% of the variance in disordered eating. The moderated mediation model including youth age accounted for 21% of the variance in disordered eating; youth age significantly interacted with sleep disturbance, but not with daytime sleepiness, to predict disordered eating. Sleep disturbance only mediated the relationship between internalizing symptoms and disordered eating in youth 12years old and younger, while daytime sleepiness was a significant mediator regardless of age. CONCLUSION: As sleep related problems are frequently improved with the adoption of health behaviors conducive to good sleep, these results may suggest a relatively modifiable and cost-effective target to reduce youth risk for disordered eating. PMID- 26826650 TI - Calcium signaling orchestrates glioblastoma development: Facts and conjunctures. AB - While it is a relatively rare disease, glioblastoma multiform (GBM) is one of the more deadly adult cancers. Following current interventions, the tumor is never eliminated whatever the treatment performed; whether it is radiotherapy, chemotherapy, or surgery. One hypothesis to explain this poor outcome is the "cancer stem cell" hypothesis. This concept proposes that a minority of cells within the tumor mass share many of the properties of adult neural stem cells and it is these that are responsible for the growth of the tumor and its resistance to existing therapies. Accumulating evidence suggests that Ca(2+) might also be an important positive regulator of tumorigenesis in GBM, in processes involving quiescence, maintenance, proliferation, or migration. Glioblastoma tumors are generally thought to develop by co-opting pathways that are involved in the formation of an organ. We propose that the cells initiating the tumor, and subsequently the cells of the tumor mass, must hijack the different checkpoints that evolution has selected in order to prevent the pathological development of an organ. In this article, two main points are discussed. (i) The first is the establishment of a so-called "cellular society," which is required to create a favorable microenvironment. (ii) The second is that GBM can be considered to be an organism, which fights to survive and develop. Since GBM evolves in a limited space, its only chance of development is to overcome the evolutionary checkpoints. For example, the deregulation of the normal Ca(2+) signaling elements contributes to the progression of the disease. Thus, by manipulating the Ca(2+) signaling, the GBM cells might not be killed, but might be reprogrammed toward a new fate that is either easy to cure or that has no aberrant functioning. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen. PMID- 26826651 TI - Aphicidal Activity of Illicium verum Fruit Extracts and Their Effects on the Acetylcholinesterase and Glutathione S-transferases Activities in Myzus persicae (Hemiptera: Aphididae). AB - This study aims to explore the aphicidal activity and underlying mechanism of Illicium verum Hook. f. that is used as both food and medicine. The contact toxicity of the extracts from I. verum fruit with methyl alcohol (MA), ethyl acetate (EA), and petroleum ether (PE) against Myzus persicae (Sulzer), and the activities of acetylcholinesterase (AChE) and glutathione S-transferases (GSTs) of M. persicae after contact treatment were tested. The results showed that MA, EA, and PE extracts of 1.000 mg/l caused, respectively, M. persicae mortalities of 68.93%, 89.95% and 74.46%, and the LC50 of MA, EA, and PE extracts were 0.31, 0.14 and 0.27 mg/l at 72 h after treatment, respectively; the activities of AChE and GSTs in M. persicae were obviously inhibited by the three extracts, as compared with the control, with strong dose and time-dependent effects, the inhibition rates on the whole reached more than 50.00% at the concentration of 1.000 mg/l at 72 h after treatment. The inhibition of the extracts on AChE and GSTs activities (EA extract > PE extract > MA extract) were correlated with theirs contact toxic effects, so it is inferred that the decline of the metabolic enzymes activities may be one of important reasons of M. persicae death. The study results suggested that I. verum extracts have potential as a eco-friendly biopesticide in integrated pest management against M. persicae. PMID- 26826652 TI - Oncogenic activation of the PI3K/Akt pathway promotes cellular glucose uptake by downregulating the expression of thioredoxin-interacting protein. AB - Oncogenic activation of the PI3K/Akt pathway is known to play an important role to promote glucose metabolism in cancer cells. However, the molecular mechanism through which the PI3K/Akt signalling pathway promotes glucose utilisation in cancer cells is still not well understood. It has recently been shown that the oncogenic activation of the PI3K/Akt/mTOR signalling in lung adenocarcinoma is important in promoting the localisation of glucose transporter 1 (GLUT1) at the plasma membrane. We thus hypothesised that the effect of constitutive activation of the PI3K/AKT signalling on glucose metabolism is mediated by thioredoxin interacting protein (TXNIP), a known regulator of the GLUT1 plasma membrane localisation. Consistent with previous studies, inhibition of the PI3K/Akt pathway decreased cellular glucose uptake. Furthermore, inhibition of PI3K/Akt signalling in non-small cell lung cancer (NSCLC) cell lines using clinically used tyrosine kinase inhibitors (TKIs) resulted in a decrease in GLUT1 membrane localisation. We also observed that inhibition of the PI3K/Akt pathway in various cell lines, including NSCLC cells, resulted in an increase in TXNIP expression. Importantly, knockdown of TXNIP using siRNA in the NSCLC cells promoted GLUT1 to be localised at the plasma membrane and reversed the effect of PI3K/Akt inhibitors. Together, our results suggest that the oncogenic activation of PI3K/Akt signalling promotes cellular glucose uptake, at least in part, through the regulation of TXNIP expression. This mechanism may contribute to the Warburg effect in cancer cells. PMID- 26826654 TI - Healing and dying with dignity: Where does India stand? PMID- 26826653 TI - The revised guidelines of the Medical Council of India for academic promotions: need for a rethink. PMID- 26826655 TI - Perceptions of stigma among medical and nursing students and tuberculosis and diabetes patients at a teaching hospital in southern India. AB - Stigma has a significant impact on the diagnosis of a variety of illnesses, patients' compliance with treatment and their recovery from these diseases. However, the Indian medical and nursing curriculum has given relatively little attention to recognising and addressing the issue of stigma. This study compared the perception of stigma with respect to tuberculosis (TB) and diabetes mellitus (DM) among medical and nursing students to that among patients with these diseases. The Explanatory Model Interview Catalogue (EMIC) questionnaire was used for all patients and student groups. Focus group discussions were held with only the students to understand their concept of stigma and the challenges they face while addressing stigma, and to explore their role in addressing stigma. The data showed that patients with TB prefer not to disclose their illness, while DM is not perceived of as stigmatising by patients. As a group, medical and nursing students attached excessive stigma to patients with both DM and TB, and this may mean that medical professionals subconsciously do harm through their interactions with patients and the attitudes they project to society. The perceptions of stigma were linked to the patient's socioeconomic background, apart from the medical condition itself. The students recognised that they lacked the skills to understand and address stigma. We recommend that the subject of stigma be integrated into the curriculum of medical and nursing students. PMID- 26826656 TI - Iranian patients' perspective of patients' rights: a qualitative study. AB - There is an increasing emphasis on "protecting patient rights", which has a great influence on the patient's well-being. This study aimed to explore patients' perspectives of patients' rights in the hospitals of Kurdistan University of Medical Sciences in Iran. This qualitative study used the content analysis method. The data were collected through in-depth interviews, conducted in Persian at the internal and surgical wards from 2012 to 2013. Consequently, interviews continued to be conducted on 20 patients, using content analysis, until data saturation. The findings highlighted aspects of patients' rights and five themes emerged from the interviews: having one's dignity respected, receiving care of the requisite quality, being shown financial consideration, receiving adequate information, and having a desirable and pleasant environment. The patients believed that for their rights to be upheld, it is necessary that together with the provision of enough facilities and equipment, they need to be respected and offered ideal healthcare services. This could be achieved by removing barriers and facilitating procedures. PMID- 26826657 TI - The caregivers' point of view. PMID- 26826658 TI - Access to palliative care: insights into ground realities post-2014 amendment to NDPS Act. AB - Medical practice today is disease-focused, ignoring the universally accepted definition of health as not just the absence of disease, but the promotion of complete physical, social and mental well-being. Generations of doctors in India have not studied modern pain management, and palliative care is practically unknown in most parts of the country, causing patients to be rejected by hospitals and doctors when they need help the most. The draconian Narcotic Drugs and Psychotropic Substances (NDPS) Act of 1985, outdated medical and nursing education, lack of public awareness and lack of clear governmental policy are responsible for this sorry state of affairs. The development of a community oriented palliative care network eventually led to the formulation of a state palliative care policy in Kerala. The acceptance of palliative care as a medical specialty by the Medical Council of India and introduction of a postgraduate degree course in palliative medicine in 2010, the development of a National Programme for Palliative Care in 2012 by the Ministry of Health of the Government of India, and the amendment of the NDPS Act in 2014 have been major positive developments which have the potential to change the current state of affairs. However, these recent achievements represent but one step in the right direction. An improvement in palliative care education, a realistic palliative care policy and implementation of the NDPS Amendment Act are necessary for doing away with the gross, needless violation of the human right to life with dignity. PMID- 26826659 TI - India: not a country to die in. AB - This commentary addresses the issue of disproportionate medical interventions for end-of-life patients. A complex mix of sociocultural and medical factors, against the backdrop of the legal milieu, has an impact on the quality of death. The barriers to appropriate end-of-life and palliative care in India are multilayered and not easy to dismantle. To raise the level of care for the dying in India, currently rated among the worst in the world, it would require no less than a nationwide movement. This paper attempts to bring into the open the areas of concern for discussion, and proposes appropriate legislation for a realistic solution. PMID- 26826660 TI - Aruna Shanbaug and the right to die with dignity: the battle continues. AB - Aruna Shanbaug's protracted continuance in a persistent vegetative state (PVS) for nearly 42 years needs to be viewed seriously by all those who believe in a person's inalienable right to dignity in dying. A terminally ill and/or incapacitated individual is a helpless person confronted with perpetual risk of intrusion in to his autonomy by the moral paternalists, owing to false notion of human virtues. Legislative inadequacy coupled with judicial heterogeneity has exposed the decision making process to unwarranted ambiguity. Misapplication of moral and juristic principles is a global challenge. 29-year-old Brittany Maynard's recent act of ending her life by migrating from California to Oregon has ignited a fierce debate and nearly half of the states in the USA are contemplating enactment of death with dignity legislation. Across the Atlantic, the European Court of Human Rights judgment on June 5, 2015, endorsing Vincent Lambert's right to end medical support, is a resounding affirmation of an individual's right to die with dignity. This article is an attempt to explore various dimensions of one's right to dignity in dying, in the global as well as the Indian context. PMID- 26826661 TI - The Allied and Healthcare Professional's Central Council Bill, 2015: more of the same. PMID- 26826662 TI - Non-psychiatrists practising psychiatry in India: ethical concerns. PMID- 26826663 TI - Indie insanity--misrepresentation of psychiatric illness in mainstream Indian cinema. PMID- 26826664 TI - Continuing dental education (CDE) points: serious concerns. PMID- 26826665 TI - Dr Ranjit Roy Chaudhury (1930-2015). PMID- 26826666 TI - Effect of suspension method on meat quality and ultra-structure of Chinese Yellow Cattle under 12-18 degrees C pre-rigor temperature controlled chilling. AB - This study was conducted to evaluate the effects of suspension method under 12-18 degrees C pre-rigor temperature controlled chilling on quality traits and ultra structure of Chinese Yellow Cattle M. Longissimus lumborum (LL). After slaughter, the right sides of carcasses were hung by the Achilles tendon (SA), while the left sides were hung from the pelvic bone (SP). Both sides went through the 12-18 degrees C pre-rigor muscle temperature controlled chilling. LL muscles were aged for 1, 7 or 14 days and then evaluated for quality traits and ultra-structure. SP had no significant effect on myofibril fragmentation index, but significantly decreased the purge loss during aging and the Warner-Bratzler shear force values after aging for 1 day. Electron microscopy and sarcomere length examination of LL showed that SP resulted in extended I-bands and sarcomere length. To conclude, applying SP under 12-18 degrees C pre-rigor temperature controlled chilling is a potential method for the Chinese beef industry to improve tenderness especially after 1 day of aging. PMID- 26826667 TI - Agonist-induced activation of histamine H3 receptor signals to extracellular signal-regulated kinases 1 and 2 through PKC-, PLD-, and EGFR-dependent mechanisms. AB - The histamine H3 receptor (H3R), abundantly expressed in the central and the peripheral nervous system, has been recognized as a promising target for the treatment of various important CNS diseases including narcolepsy, Alzheimer's disease, and attention deficit hyperactivity disorder. The H3R acts via Gi/o proteins to inhibit adenylate cyclase activity and modulate MAPK activity. However, the underlying molecular mechanisms for H3R mediation of the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) remain to be elucidated. In this study, using HEK293 cells stably expressing human H3R and mouse primary cortical neurons endogenously expressing mouse H3R, we found that the H3R-mediated activation of ERK1/2 was significantly blocked by both the pertussis toxin and the MEK1/2 inhibitor U0126. Upon stimulation by H3R agonist histamine or imetit, H3R was shown to rapidly induce ERK1/2 phosphorylation via PLC/PKC-, PLDs-, and epidermal growth factor receptor (EGFR) transactivation dependent pathways. Furthermore, it was also indicated that while the betagamma subunits play a key role in H3R-activated ERK1/2 phosphorylation, beta-arrestins were not required for ERK1/2 activation. In addition, when the cultured mouse cortical neurons were exposed to oxygen and glucose deprivation conditions (OGD), imetit exhibited neuroprotective properties through the H3R. Treatment of cells with the inhibitor UO126 abolished these protective effects. This suggests a possible neuroprotective role of the H3R-mediated ERK1/2 pathway under hypoxia conditions. These observations may provide new insights into the pharmacological effects and the physiological functions modulated by the H3R-mediated activation of ERK1/2. Histamine H3 receptors are abundantly expressed in the brain and play important roles in various CNS physiological functions. However, the underlying mechanisms for H3R-induced activation of extracellular signal-regulated kinase (ERK)1/2 remain largely unknown. Here, we provide evidence that upon activation by an agonist, H3Rs trigger ERK1/2 activation via phospholipase C/protein kinase C (PLC/PKC)-, phospholipase D (PLD)s-, and matrix metallopeptidase/epidermal growth factor receptor (MMP/EGFR) transactivation-dependent pathways. Moreover, we demonstrate that H3Rs exhibit a neuroprotective effect on the cultured mouse cortical neurons under hypoxia conditions through the ERK1/2 pathway. PMID- 26826669 TI - Inflammation in Alcoholic and Nonalcoholic Fatty Liver Disease: Friend or Foe? PMID- 26826668 TI - Detecting hybridization using ancient DNA. AB - It is well established that related species hybridize and that this can have varied but significant effects on speciation and environmental adaptation. It should therefore come as no surprise that hybridization is not limited to species that are alive today. In the last several decades, advances in technologies for recovering and sequencing DNA from fossil remains have enabled the assembly of high-coverage genome sequences for a growing diversity of organisms, including many that are extinct. Thanks to the development of new statistical approaches for detecting and quantifying admixture from genomic data, genomes from extinct populations have proven useful both in revealing previously unknown hybridization events and informing the study of hybridization between living organisms. Here, we review some of the key recent statistical innovations for detecting ancient hybridization using genomewide sequence data and discuss how these innovations have revised our understanding of human evolutionary history. PMID- 26826671 TI - Swimming speed alteration in the early developmental stages of Paracentrotus lividus sea urchin as ecotoxicological endpoint. AB - Behavioral endpoints have been used for decades to assess chemical impacts at concentrations unlikely to cause mortality. With recently developed techniques, it is possible to investigate the swimming behavior of several organisms under laboratory conditions. The aims of this study were: i) assessing for the first time the feasibility of swimming speed analysis of the early developmental stage sea urchin Paracentrotus lividus by an automatic recording system ii) investigating any Swimming Speed Alteration (SSA) on P. lividus early stages exposed to a chemical reference; iii) identifying the most suitable stage for SSA test. Results show that the swimming speed of all the developmental stages was easily recorded. The swimming speed was inhibited as a function of toxicant concentration. Pluteus were the most appropriate stage for evaluating SSA in P. lividus as ecotoxicological endpoint. Finally, swimming of sea urchin early stages represents a sensitive endpoint to be considered in ecotoxicological investigations. PMID- 26826670 TI - Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis. AB - Age-related loss of muscle mass and strength can be accelerated by impaired recovery of muscle mass following a transient atrophic stimulus. The aim of this study was to identify the mechanisms underlying the attenuated recovery of muscle mass and strength in old rats following disuse-induced atrophy. Adult (9 month) and old (29 month) male F344BN rats underwent hindlimb unloading (HU) followed by reloading. HU induced significant atrophy of the hindlimb muscles in both adult (17-38%) and old (8-29%) rats, but only the adult rats exhibited full recovery of muscle mass and strength upon reloading. Upon reloading, total RNA and protein synthesis increased to a similar extent in adult and old muscles. At baseline and upon reloading, however, proteasome-mediated degradation was suppressed leading to an accumulation of ubiquitin-tagged proteins and p62. Further, ER stress, as measured by CHOP expression, was elevated at baseline and upon reloading in old rats. Analysis of mRNA expression revealed increases in HDAC4, Runx1, myogenin, Gadd45a, and the AChRs in old rats, suggesting neuromuscular junction instability/denervation. Collectively, our data suggests that with aging, impaired neuromuscular transmission and deficits in the proteostasis network contribute to defects in muscle fiber remodeling and functional recovery of muscle mass and strength. PMID- 26826672 TI - Association of sleep bruxism and dental plaque factors on signs of periodontal disease in children in the mixed dentition. AB - BACKGROUND: Periodontal disease has a multifactorial etiology; however, dental plaque and possible sleep bruxism (SB) have not been tested together in children as predictors of periodontal disease. AIM: To assess the variation of SB, dental biofilm (DBF), gingival index (GI), and plaque index (PI) between localized and generalized pathological probing depth (PPD), crestal bone loss (CBL), and lack of delineation of lamina dura (LD) and to establish the association of DBF, GI, PI and SB with PPD, CBL, and LD in children with mixed dentition. METHODS: Fifty children were assessed for SB and underwent a clinical and radiographic periodontal examination. anova and three multiple variable analysis were used to analyze the data. RESULTS: One-way anova was found to be statistically significant for SB, between localized and generalized PPD (P = 0.03), CBL (P = 0.01), and LD (P = 0.005) and for DBF between localized and generalized CBL (P = 0.02). The three multiple variable analysis showed statistically and clinically significant associations of DBF with PPD (OR = 3.33); GI (OR = 2.37), and PI (OR = 1.46) with CBL and SB (OR = 7.66) and DBF (OR = 9.87) with LD. PI presented statistically significant association with CBL. CONCLUSION: Significant associations of SB, DBF, GI, and PI with PD, CBL, and LD and the variations of the same factors between localized and generalized PPD, CBL, and LD suggest the necessity of evaluating SB, DBF, GI, and PI when children are screened in regular dental visits. PMID- 26826673 TI - Stereoselective pharmacokinetic and metabolism studies of 20(S)- and 20(R) ginsenoside Rg3 epimers in rat plasma by liquid chromatography-electrospray ionization mass spectrometry. AB - 20(S)- and 20(R)-ginsenoside Rg3 are a pair of epimers which could be deglycosylated to ginsenoside Rh2 and protopanaxadiol (PPD) in vivo. To better understand the differences of pharmacokinetic parameters and metabolism behaviors of Rg3 epimers in rat plasma, a sensitive and specific liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and fully validated. This chromatographic method separate 20(S)-/20(R)-Rg3, 20(S)-/20(R) Rh2 and 20(S)-/20(R)-PPD by gradient elution of 10 mM ammonium acetate solution (pH 5.0) and acetonitrile on a C18 column with a total run time of 15 min. 20(S) protopanaxatriol (PPT) was used as internal standard, and multiple reaction monitoring (MRM) mode with negative electrospray ionization were performed. The lower limit of quantitations (LLOQs) were between 4.2 and 4.8 ng/ml, and the accuracies were between 91.7% and 112.2% with intra- and inter-day precisions less than 11.6%. This method was successfully applied to a pharmacokinetic study of intravenous and intra-gastric administration of 20(S)-Rg3 and 20(R)-Rg3 to rats. It has been found that both epimers can be deglycosylated to their corresponding chiral metabolites, i.e., Rh2 and PPD, with different extents. However, 20(R)-Rg3 underwent single direction chiral inversion to 20(S)-Rg3 in rats. Stereoselective pharmacokinetic parameters, metabolic degrees and chiral inversion extents of Rg3 epimers in rats were also discussed for the first time. PMID- 26826674 TI - Scaffold-free Tissue Formation Under Real and Simulated Microgravity Conditions. AB - Scaffold-free tissue formation in microgravity is a new method in regenerative medicine and an important topic in Space Medicine. In this MiniReview, we focus on recent findings in the field of tissue engineering that were observed by exposing cells to real microgravity in space or to devices simulating to at least some extent microgravity conditions on Earth (ground-based facilities). Under both conditions - real and simulated microgravity - a part of the cultured cells of various populations detaches from the bottom of a culture flask. The cells form three-dimensional (3D) aggregates resembling the organs from which the cells have been derived. As spaceflights are rare and extremely expensive, cell culture under simulated microgravity allows more comprehensive and frequent studies on the scaffold-free 3D tissue formation in some aspects, as a number of publications have proven during the last two decades. In this MiniReview, we summarize data from our own studies and work from various researchers about tissue engineering of multi-cellular spheroids formed by cancer cells, tube formation by endothelial cells and cartilage formation by exposing the cells to ground-based facilities such as the 3D Random Positioning Machine (RPM), the 2D Fast-Rotating Clinostat (FRC) or the Rotating Wall Vessel (RWV). Subsequently, we investigated self-organization of 3D aggregates without scaffolds pursuing to enhance the frequency of 3D formation and to enlarge the size of the organ-like aggregates. The density of the monolayer exposed to real or simulated microgravity as well as the composition of the culture media revealed an impact on the results. Genomic and proteomic alterations were induced by simulated microgravity. Under microgravity conditions, adherent cells expressed other genes than cells grown in spheroids. In this MiniReview, the recent improvements in scaffold-free tissue formation are summarized and relationships between phenotypic and molecular appearance are highlighted. PMID- 26826675 TI - The Opioid Rotation Ratio From Transdermal Fentanyl to "Strong" Opioids in Patients With Cancer Pain. AB - CONTEXT: One-third of cancer patients require opioid rotation (OR) to treat uncontrolled pain or opioid-induced neurotoxicity. Although fentanyl is the most frequently rotated opioid in cancer patients, the accurate opioid rotation ratio (ORR) from transdermal fentanyl (TDF) to other so-called "strong" opioids is unknown. OBJECTIVES: We aimed to determine the ORR of TDF to strong opioids, as measured by morphine equivalent daily dose (MEDD). METHODS: We reviewed 2471 consecutive patient visits (938 patients) to our supportive care center for an OR from TDF to strong opioids. Information regarding demographics, symptoms, and MEDD was collected in patients who followed up within six weeks. Linear regression analysis was used to estimate the ORR between TDF dose and net MEDD (MEDD after OR minus MEDD of the breakthrough opioid used along with TDF before OR). RESULTS: Among 47 eligible patients, the median age was 54 years, 53% were male, and 77% had advanced cancer. The median time to follow-up was 14 days. Uncontrolled pain (83%) was the most common reason for OR. In patients with OR and no worsening of pain at follow-up (n = 41), the median ORR (range) from TDF mg/day to net MEDD mg/day was 100 (12.5-217) and from TDF mcg/hour to net MEDD was 2.4 (0.3-5.2); the correlation of TDF dose to net MEDD was 0.60 (P < 0.0001). CONCLUSION: The median ORR from TDF mg/day to MEDD is 100 and from TDF mcg/hour to MEDD is 2.4, suggesting that TDF 100 mcg/hour is equivalent to an MEDD of 240 mg. PMID- 26826676 TI - Clinical Implications of C-Reactive Protein as a Prognostic Marker in Advanced Cancer Patients in Palliative Care Settings. AB - CONTEXT: Plasma C-reactive protein (CRP) levels are elevated in patients with advanced cancer. OBJECTIVES: To investigate CRP as a prognostic marker in palliative settings. METHODS: This multicenter prospective cohort study comprised 2426 patients. Laboratory data were obtained at baseline, and all patients were followed until death or six months after their enrollment. A total of 1511 patients were eligible for the analyses. They were divided into four groups: low CRP (CRP < 1 mg/dL), moderate-CRP (1 <= CRP <5 mg/dL), high-CRP (5 <= CRP <10 mg/dL), and very high-CRP (10 mg/dL <= CRP) groups. Survival was investigated by the Kaplan-Meier method with the log-rank test. The 30-, 60-, and 90-day mortality rates were tested by Chi-squared tests. Univariate- and multivariate adjusted hazard ratios (HRs) and 95% CIs in each group were calculated using Cox proportional hazard models. RESULTS: Survival rate decreased and mortality rate increased with increasing CRP level. The differences in survival and 30-, 60-, and 90-day mortality rates among the groups were statistically significant (P < 0.001). Baseline CRP level was significantly associated with a higher risk of mortality after adjustment for age, gender, primary tumor site, metastasis, chemotherapy, Eastern Cooperative Oncology Group Performance Status, and setting of care (moderate-CRP: HR 1.47 [95% CI 1.24-1.73], high-CRP: HR 2.09 [95% CI 1.74 2.50], and very high-CRP: HR 2.55 [95% CI 2.13-3.05] vs. low-CRP). CONCLUSION: Clear dose-effect relationships between elevated CRP levels and prognoses indicate that CRP could be useful in predicting prognoses in patients with advanced cancer. PMID- 26826677 TI - Physicians' and Nurse Practitioners' Level of Pessimism About End-of-Life Care During Training: Does It Change Over Time? AB - CONTEXT: An enhanced understanding of trainee attitudes about end-of-life care is needed to inform interventions to improve clinician communication about dying and death. OBJECTIVES: To examine changes in trainee pessimism about end-of-life care over the course of one academic year and to explore predictors of pessimism among residents, fellows, and nurse practitioners. METHODS: We used baseline and follow up surveys completed by trainees during a randomized controlled trial of an intervention to improve clinician communication skills. Surveys addressed trainee feelings about end-of-life care. Latent variable modeling was used to identify indicators of trainee pessimism, and this pessimism construct was used to assess temporal changes in trainee attitudes about end-of-life care. We also examined predictors of trainee pessimism at baseline and follow-up. Data were available for 383 trainees from two training programs. RESULTS: There was a significant decrease in pessimism between baseline and follow-up assessments. Age had a significant inverse effect on baseline pessimism, with older trainees being less pessimistic. There was a direct association of race/ethnicity on pessimism at follow-up, with greater pessimism among minority trainees (P = 0.028). The model suggests that between baseline and follow-up, pessimism among younger white non Hispanic trainees decreased, whereas pessimism among younger trainees in racial/ethnic minorities increased over the same period. CONCLUSION: Overall, trainee pessimism about end-of-life care decreases over time. Pessimism about end of-life care among minority trainees may reflect the influence of culture on clinician attitudes about communication with seriously ill patients. Further research is needed to understand the evolution of trainee attitudes about end-of life care during clinical training. PMID- 26826678 TI - Recurrent Hemoperitoneum During Pregnancy in Large Deep Endometriosis Infiltrating the Parametrium. AB - We present the case of a young woman at 16 weeks' gestation who presented to a peripheral hospital with severe recurrent hemoperitoneum related to severe deep endometriosis infiltrating the left parametrium. She underwent 2 surgical open procedures in emergency, followed by pregnancy loss. Deep endometriosis infiltrated the rectum, the vagina, and the left parametrium, leading to stenosis of the left ureter and advanced destruction of the left kidney. Ovarian reserve was low with an antimullerian hormone level at .6 ng/mL. To improve endometriosis related symptoms and preserve fertility, a laparoscopic conservative rectal and ureteral management was proposed with an aim to relieve symptoms, avoid further destruction of the left kidney, preserve the right splanchnic nerves and inferior hypogastric plexus, and enhance spontaneous conception. We performed a combined vaginal-laparoscopic approach that consisted of vaginal infiltration resection, adhesiolysis, rectal shaving, ureterolysis, and restoration of the permeability of the fallopian tubes. Seven months after surgery the patient spontaneously conceived and is doing well. PMID- 26826679 TI - Mode of action based risk assessment of the botanical food-borne alkenylbenzene apiol from parsley using physiologically based kinetic (PBK) modelling and read across from safrole. AB - The present study developed physiologically-based kinetic (PBK) models for the alkenylbenzene apiol in order to facilitate risk assessment based on read-across from the related alkenylbenzene safrole. Model predictions indicate that in rat liver the formation of the 1'-sulfoxy metabolite is about 3 times lower for apiol than for safrole. These data support that the lower confidence limit of the benchmark dose resulting in a 10% extra cancer incidence (BMDL10) that would be obtained in a rodent carcinogenicity study with apiol may be 3-fold higher for apiol than for safrole. These results enable a preliminary risk assessment for apiol, for which tumor data are not available, using a BMDL10 value of 3 times the BMDL10 for safrole. Based on an estimated BMDL10 for apiol of 5.7-15.3 mg/kg body wt per day and an estimated daily intake of 4 * 10(-5) mg/kg body wt per day, the margin of exposure (MOE) would amount to 140,000-385,000. This indicates a low priority for risk management. The present study shows how PBK modelling can contribute to the development of alternatives for animal testing, facilitating read-across from compounds for which in vivo toxicity studies on tumor formation are available to compounds for which these data are unavailable. PMID- 26826680 TI - Liquid-like behavior of chromatin. AB - Eukaryotic chromatin is a negatively charged long polymer composed of genomic DNA, histones, and various proteins. The charged property causes the chromatin structure to be dynamically changed. These dynamic changes are critical for genome functions such as gene expression because they directly govern the degree of DNA accessibility. Although the chromatin structure is not yet fully understood, currently increasing evidence suggests that chromatin has a dynamic liquid-like structure based on the 10-nm fiber but not the 30-nm fiber. This liquid-like property can drive the process of 'scanning and targeting genomic DNA,' which contributes to various genome functions including gene expression and DNA replication, repair, and recombination. Here, we discuss the liquid-like behavior of chromatin and its physical and biological relevance. PMID- 26826682 TI - Increased risk of colorectal cancer in patients diagnosed with breast cancer in women. AB - BACKGROUND: Epidemiological studies have shown a potential association between sex hormones and colorectal cancer. The risk of colorectal cancer in breast cancer patients who may have been exposed to increased levels of endogenous sex hormones and/or exogenous sex hormones (e.g. anti-hormonal therapy) has not been thoroughly evaluated. METHODS: Using the National Swedish Cancer Register we established a population-based prospective cohort of breast cancer patients in women diagnosed in Sweden between 1961 and 2010. Subsequent colorectal cancers were identified from the same register. Standardized incidence ratios (SIRs) and 95% confidence intervals (95%CIs) were used to estimate the risk of colorectal cancer after a diagnosis of breast cancer. The association between breast cancer therapy and risk of colorectal cancer was evaluated in a subcohort of breast cancer patients treated in Stockholm between 1977 and 2007. Hazard ratios (HRs) and 95%CIs were estimated using Cox regression models. RESULTS: In a cohort of 179,733 breast cancer patients in Sweden, 2571 incident cases of colorectal cancer (1008 adenocarcinomas in the proximal colon, 590 in the distal colon and 808 in the rectum) were identified during an average follow-up of 9.68 years. An increased risk of colorectal adenocarcinoma was observed in the breast cancer cohort compared with that in the general population (SIR=1.59, 95%CI: 1.53, 1.65). Adenocarcinoma in the proximal colon showed a non-significantly higher SIR (1.72, 95%CI: 1.61, 1.82) compared with the distal colon (1.46, 95%CI: 1.34, 1.58). In the subcohort of 20,171 breast cancers with available treatment data, 299 cases with colorectal cancers were identified. No treatment-dependent risk of colorectal cancer was observed among the breast cancer patients. CONCLUSION: An increased risk of colorectal adenocarcinoma - especially in the proximal colon - was observed in the breast cancer cohort. Breast cancer treatment did not alter this risk. PMID- 26826681 TI - Pioneer transcription factors, chromatin dynamics, and cell fate control. AB - Among the diverse transcription factors that are necessary to elicit changes in cell fate, both in embryonic development and in cellular reprogramming, a subset of factors are capable of binding to their target sequences on nucleosomal DNA and initiating regulatory events in silent chromatin. Such 'pioneer transcription factors' initiate cooperative interactions with other regulatory proteins to elicit changes in local chromatin structure. As a consequence of pioneer factor binding, the local chromatin can either become open and competent for activation, closed and repressed, or transcriptionally active. Understanding how pioneer factors initiate chromatin dynamics and how such can be blocked at heterochromatic sites provides insights into controlling cell fate transitions at will. PMID- 26826683 TI - The effect of economic insecurity on mental health: Recent evidence from Australian panel data. AB - This paper estimates the impact of economic insecurity on the mental health of Australian adults. Taking microdata from the 2001-2011 HILDA panel survey, we develop a conceptually diverse set of insecurity measures and explore their relationships with the SF-36 mental health index. By using fixed effects models that control for unobservable heterogeneity we produce estimates that correct for endogeneity more thoroughly than previous works. Our results show that exposure to economic risks has small but consistently detrimental mental health effects. The main contribution of the paper however comes from the breadth of risks that are found to be harmful. Job insecurity, financial dissatisfaction, reductions and volatility in income, an inability to meet standard expenditures and a lack of access to emergency funds all adversely affect health. This suggests that the common element of economic insecurity (rather than idiosyncratic phenomena associated with any specific risk) is likely to be hazardous. Our preferred estimates indicate that a standard deviation shock to economic insecurity lowers an individual's mental health score by about 1.4 percentage points. If applied uniformly across the Australian population such a shock would increase the morbidity rate of mental disorders by about 1.7%. PMID- 26826684 TI - Complete suppression of the fluorophore fluorescence by combined effect of multiple fluorescence quenching groups: A fluorescent sensor for Cu2+ with zero background signals. AB - The reaction-based fluorescent sensors have attracted increasing attention in the past decades. However, the application of these sensors for accurate sensing was significantly retarded by the background fluorescence from the sensors themselves. In this work, we demonstrated a novel strategy that the background fluorescence of the sensor could be completely eliminated by the combined effect of multiple fluorescence quenching groups. Based on this new strategy, as proof of-principle study, a fluorescent sensor (CuFS) for Cu(2+) was judiciously developed. In CuFS, three types of fluorescence quenching groups were directly tethered to a commonly used coumarin fluorophore. The fluorescence of coumarin fluorophore in CuFS was completely suppressed by the combined effect of these fluorescence quenching groups. Upon treatment with 22 MUM Cu(2+), sensor CuFS achieved a dramatic fluorescence enhancement (fluorescence intensity enhanced up to 811-fold) centered at 469 nm. The detection limits was determined to be 12.3 nM. The fluorescence intensity enhancement also showed a good linearity with the Cu(2+) concentration in the range of 12.3 nM to 2 MUM. By fabricating test strips, sensor CuFS can be utilized as a simple tool to detect Cu(2+) in water samples. Furthermore, the fluorescent sensor was successfully applied in detecting different concentration of Cu(2+) in living cells. PMID- 26826685 TI - New advances in electrochemical biosensors for the detection of toxins: Nanomaterials, magnetic beads and microfluidics systems. A review. AB - The use of nanotechnology in bioanalytical devices has special advantages in the detection of toxins of interest in food safety and environmental applications. The low levels to be detected and the small size of toxins justify the increasing number of publications dealing with electrochemical biosensors, due to their high sensitivity and design versatility. The incorporation of nanomaterials in their development has been exploited to further increase their sensitivity, providing simple and fast devices, with multiplexed capabilities. This paper gives an overview of the electrochemical biosensors that have incorporated carbon and metal nanomaterials in their configurations for the detection of toxins. Biosensing systems based on magnetic beads or integrated into microfluidics systems have also been considered because of their contribution to the development of compact analytical devices. The roles of these materials, the methods used for their incorporation in the biosensor configurations as well as the advantages they provide to the analyses are summarised. PMID- 26826686 TI - Analytical methods for the determination of mixtures of bisphenols and derivatives in human and environmental exposure sources and biological fluids. A review. AB - Bisphenol A (BPA) is ubiquitous in humans and the environment. Its potential adverse effects through genomic and non-genomic pathways have fostered BPA replacement by bisphenol analogs that, unfortunately, exert similar adverse effects. Many of these analogs, as well as their derivatives, have already found in humans and the environment and major concerns have arisen over their low dose- and mixture-related effects. This review aims to discuss the characteristics of the main analytical methods reported so far for the determination of mixtures of bisphenol analogs and/or derivatives in human and environmental exposure sources and biological fluids. Approaches followed for removal of background contamination, sample preparation and separation and detection of mixtures of bisphenols and derivatives are critically discussed. Sample treatment is matrix dependent and common steps include analyte isolation, removal of interferences, evaporation of the extracts and solvent reconstitution. Separation and quantification has been almost exclusively carried out by liquid chromatography tandem mass spectrometry (LC-MS/MS) or gas chromatography mass spectrometry (GC MS), in the last case prior derivatization, but LC-fluorescence detection has also found some applications. Main characteristics, advantages and drawbacks of these methods will be comparatively discussed. Although at an early stage, some approaches for the assessment of the risk to mixtures of bisphenols, mainly based on the combination of chemical target analysis and toxicity evaluation, have been already applied and they will be here presented. Current knowledge gaps hindering a reliable assessment of human and environmental risk to mixtures of bisphenols and derivatives will be outlined. PMID- 26826687 TI - Application of dried-droplets deposited on pre-cut filter paper disks for quantitative LA-ICP-MS imaging of biologically relevant minor and trace elements in tissue samples. AB - In this work, a novel calibration approach for minor and trace element quantification in LA-ICP-MS imaging of biological tissues is presented. Droplets of aqueous standard solutions are deposited onto pre-cut pieces of filter paper, allowed to dry, and sputtered with a thin gold layer for use as pseudo-internal standard. Analysis of the standards using LA-ICP-MS is performed using radial line-scans across the filters. In contrast to conventionally used preparation of matrix-matched tissue standards, the dried-droplet approach offers a variety of advantages: The standards are easy to prepare, no characterization of the standards using acid digestion is required, no handling of biological materials is necessary, and the concentration range, as well the number of investigated analytes is almost unlimited. The proposed quantification method has been verified using homogenized tissue standards with known analyte concentrations before being applied to a human malignant mesothelioma biopsy from a patient who had not received any chemotherapeutic treatment. Elemental distribution images were acquired at a lateral resolution of 40 MUm per pixel, limits of detection ranging from 0.1 MUg g(-1) (Mn, Ni, Cu, Zn) to 13.2 MUg g(-1) (K) were reached. PMID- 26826688 TI - A bootstrapping soft shrinkage approach for variable selection in chemical modeling. AB - In this study, a new variable selection method called bootstrapping soft shrinkage (BOSS) method is developed. It is derived from the idea of weighted bootstrap sampling (WBS) and model population analysis (MPA). The weights of variables are determined based on the absolute values of regression coefficients. WBS is applied according to the weights to generate sub-models and MPA is used to analyze the sub-models to update weights for variables. The optimization procedure follows the rule of soft shrinkage, in which less important variables are not eliminated directly but are assigned smaller weights. The algorithm runs iteratively and terminates until the number of variables reaches one. The optimal variable set with the lowest root mean squared error of cross-validation (RMSECV) is selected. The method was tested on three groups of near infrared (NIR) spectroscopic datasets, i.e. corn datasets, diesel fuels datasets and soy datasets. Three high performing variable selection methods, i.e. Monte Carlo uninformative variable elimination (MCUVE), competitive adaptive reweighted sampling (CARS) and genetic algorithm partial least squares (GA-PLS) are used for comparison. The results show that BOSS is promising with improved prediction performance. The Matlab codes for implementing BOSS are freely available on the website: http://www.mathworks.com/matlabcentral/fileexchange/52770-boss. PMID- 26826689 TI - Confidence limits for contribution plots in multivariate statistical process control using bootstrap estimates. AB - In Multivariate Statistical Process Control, when a fault is expected or detected in the process, contribution plots are essential for operators and optimization engineers in identifying those process variables that were affected by or might be the cause of the fault. The traditional way of interpreting a contribution plot is to examine the largest contributing process variables as the most probable faulty ones. This might result in false readings purely due to the differences in natural variation, measurement uncertainties, etc. It is more reasonable to compare variable contributions for new process runs with historical results achieved under Normal Operating Conditions, where confidence limits for contribution plots estimated from training data are used to judge new production runs. Asymptotic methods cannot provide confidence limits for contribution plots, leaving re-sampling methods as the only option. We suggest bootstrap re-sampling to build confidence limits for all contribution plots in online PCA-based MSPC. The new strategy to estimate CLs is compared to the previously reported CLs for contribution plots. An industrial batch process dataset was used to illustrate the concepts. PMID- 26826690 TI - Mapping Cd2+-induced membrane permeability changes of single live cells by means of scanning electrochemical microscopy. AB - Scanning Electrochemical Microscopy (SECM) is a powerful, non-invasive, analytical methodology that can be used to investigate live cell membrane permeability. Depth scan SECM imaging allowed for the generation of 2D current maps of live cells relative to electrode position in the x-z or y-z plane. Depending on resolution, one depth scan image can contain hundreds of probe approach curves (PACs). Individual PACs were obtained by simply extracting vertical cross-sections from the 2D image. These experimental PACs were overlaid onto theoretically generated PACs simulated at specific geometry conditions. Simulations were carried out using 3D models in COMSOL Multiphysics to determine the cell membrane permeability coefficients at different locations on the surface of the cells. Common in literature, theoretical PACs are generated using a 2D axially symmetric geometry. This saves on both compute time and memory utilization. However, due to symmetry limitations of the model, only one experimental PAC right above the cell can be matched with simulated PAC data. Full 3D models in this article were developed for the SECM system of live cells, allowing all experimental PACs over the entire cell to become usable. Cd(2+) induced membrane permeability changes of single human bladder (T24) cells were investigated at several positions above the cell, displaced from the central axis. The experimental T24 cells under study were incubated with Cd(2+) in varying concentrations. It is experimentally observed that 50 and 100 MUM Cd(2+) caused a decrease in membrane permeability, which was uniform across all locations over the cell regardless of Cd(2+) concentration. The Cd(2+) was found to have detrimental effects on the cell, with cells shrinking in size and volume, and the membrane permeability decreasing. A mapping technique for the analysis of the cell membrane permeability under the Cd(2+) stress is realized by the methodology presented. PMID- 26826691 TI - A regenerative ratiometric electrochemical biosensor for selective detecting Hg2+ based on Y-shaped/hairpin DNA transformation. AB - Inspired by dual-signaling ratiometric mechanism which could reduce the influence of the environmental change, a novel, convenient, and reliable method for the detection of mercury ions (Hg(2+)) based on Y-shaped DNA (Y-DNA) was developed. Firstly, the Y-DNA was formed via the simple annealing way of using two different redox probes simultaneously, omitting the multiple operation steps on the electrode. The Y-DNA was immobilized on the gold electrode surface and then an obvious ferrocene (Fc) signal and a weak methylene blue (MB) signal were observed. Upon addition of Hg(2+), the Y-DNA structure was transformed to hairpin structure based on the formation of T-Hg(2+)-T complex. During the transformation, the redox MB gets close to and the redox Fc gets far away from the electrode surface, respectively. This special design allows a reliable Hg(2+) detection with a detection range from 1 nM to 5 MUM and a low detection limit down to 0.094 nM. Furthermore, this biosensor exhibits good selectivity and repeatability, and can be easily regenerated by using L-cysteine. This study offers a simple and effective method for designing ratiometric biosensors for detecting other ions and biomolecules. PMID- 26826692 TI - Validation and modelling of a novel diffusive sampler for determining concentrations of volatile organic compounds in air. AB - A novel diffusive sampler that combines radial and axial diffusion has been developed that improves upon existing commercially available designs. The POcket Diffusive (POD) sampler has been validated under laboratory and field conditions for the measurements of VOCs in ambient air. Laboratory tests varied sampling conditions of temperature (-30-40 C), humidity (10-80%), wind velocity (0.1-4 m s(-1)), and concentration (0.5-50 MUg m(-3)) for a number of specific VOCs. An overall uncertainty of circa 9% for the measurement of benzene is calculated for the validation tests, in compliance with the data quality objectives of the EU air quality directive 2008/50/EC. A semi-empirical diffusion model has been developed to estimate sampling rates for compounds that were not tested, and for conditions outside of tested ranges during validation. The diffusion model (and validation tests) shows a low influence of environmental conditions on the sampling rate for the POD sampler. Average reproducibility values of circa 3% are reported with overall sampling uncertainties ranging from 9% to 15%, for the whole range of tested conditions, depending on the compound. The adsorbent cartridge is compatible with existing thermal desorption systems in the market. The diffusive sampler can modify the sampling rate by changing the diffusive body within a range of different porosities. Field tests, conducted in parallel with independent quality controlled canister sampling, confirmed the ease of use and quality of VOC measurements with the POD sampler, for compounds that were, and were not, evaluated during laboratory tests. PMID- 26826693 TI - Simultaneous micro-electromembrane extractions of anions and cations using multiple free liquid membranes and acceptor solutions. AB - Micro-electromembrane extractions (MU-EMEs) across free liquid membranes (FLMs) were applied to simultaneous extractions of anions and cations. A transparent narrow-bore polymeric tubing was filled with adjacent plugs of MUL volumes of aqueous and organic solutions, which formed a stable five-phase MU-EME system. For the simultaneous MU-EMEs of anions and cations, aqueous donor solution was the central phase, which was sandwiched between two organic FLMs and two aqueous acceptor solutions. On application of electric potential, anions and cations in the donor solution migrated across the two FLMs and into the two peripheral acceptor solutions in the direction of anode and cathode, respectively. Visual monitoring of anionic (tartrazine) and cationic (phenosafranine) dye confirmed their simultaneous MU-EMEs and their rapid (in less than 5 min) transfers into anolyte and catholyte, respectively. The concept of simultaneous MU-EMEs was further examined with selected model analytes; KClO4 was used for MU-EMEs of inorganic anions and cations and ibuprofen and procaine for MU-EMEs of acidic and basic drugs. Quantitative analyses of the resulting acceptor solutions were carried out by capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C(4)D). Good extraction recoveries (91-94%) and repeatability of peak areas (<=6.3%) were achieved for 5 min MU-EMEs of K(+) and ClO4(-). Extraction recoveries and repeatability of peak areas for 5 min MU-EMEs of ibuprofen and procaine were also satisfactory and ranged from 35 to 63% and 7.6 to 11.3%, respectively. Suitability of the presented micro-extraction procedure was further demonstrated on simultaneous MU-EMEs with subsequent CE C(4)D of ibuprofen and procaine from undiluted human urine samples. PMID- 26826694 TI - Postprandial metabolomics: A pilot mass spectrometry and NMR study of the human plasma metabolome in response to a challenge meal. AB - The study of postprandial metabolism is relevant for understanding metabolic diseases and characterizing personal responses to diet. We combined three analytical platforms - gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) - to validate a multi-platform approach for characterizing individual variation in the postprandial state. We analyzed the postprandial plasma metabolome by introducing, at three occasions, meal challenges on a usual diet, and 1.5 years later, on a modified background diet. The postprandial response was stable over time and largely independent of the background diet as revealed by all three analytical platforms. Coverage of the metabolome between NMR and GC-MS included more polar metabolites detectable only by NMR and more hydrophobic compounds detected by GC-MS. The variability across three separate testing occasions among the identified metabolites was in the range of 1.1-86% for GC-MS and 0.9-42% for NMR in the fasting state at baseline. For the LC-MS analysis, the coefficients of variation of the detected compounds in the fasting state at baseline were in the range of 2-97% for the positive and 4-69% for the negative mode. Multivariate analysis (MVA) of metabolites detected with GC-MS revealed that for both background diets, levels of postprandial amino acids and sugars increased whereas those of fatty acids decreased at 0.5 h after the meal was consumed, reflecting the expected response to the challenge meal. MVA of NMR data revealed increasing postprandial levels of amino acids and other organic acids together with decreasing levels of acetoacetate and 3-hydroxybutanoic acid, also independent of the background diet. Together these data show that the postprandial response to the same challenge meal was stable even though it was tested 1.5 years apart, and that it was largely independent of background diet. This work demonstrates the efficacy of a multi-platform metabolomics approach followed by multivariate and univariate data analysis for a broad-scale screen of the individual metabolome, particularly for studies using repeated measures to determine dietary response phenotype. PMID- 26826696 TI - Diamond nanoparticles as a way to improve electron transfer in sol-gel L-lactate biosensing platforms. AB - In the present work, we have included for the first time diamond nanoparticles (DNPs) in a sol-gel matrix derived from (3-mercaptopropyl)-trimethoxysilane (MPTS) in order to improve electron transfer in a lactate oxidase (LOx) based electrochemical biosensing platform. Firstly, an exhaustive AFM study, including topographical, surface potential (KFM) and capacitance gradient (CG) measurements, of each step involved in the biosensing platform development was performed. The platform is based on gold electrodes (Au) modified with the sol gel matrix (Au/MPTS) in which diamond nanoparticles (Au/MPTS/DNPs) and lactate oxidase (Au/MPTS/DNPs/LOx) have been included. For the sake of comparison, we have also characterized a gold electrode directly modified with DNPs (Au/DNPs). Secondly, the electrochemical behavior of a redox mediator (hydroxymethyl ferrocene, HMF) was evaluated at the platforms mentioned above. The response of Au/MPTS/DNPs/LOx towards lactate was obtained. A linear concentration range from 0.053 mM to 1.6 mM, a sensitivity of 2.6 MUA mM(-1) and a detection limit of 16 MUM were obtained. These analytical properties are comparable to other biosensors, presenting also as advantages that DNPs are inexpensive, environment friendly and easy-handled nanomaterials. Finally, the developed biosensor was applied for lactate determination in wine samples. PMID- 26826695 TI - Benzylic rearrangement stable isotope labeling for quantitation of guanidino and ureido compounds in thyroid tissues by liquid chromatography-electrospray ionization mass spectrometry. AB - Benzylic rearrangement stable isotope labeling (BRSIL) was explored to quantify the guanidino and ureido compounds (GCs and UCs). This method employed a common reagent, benzil, to label the guanidino and ureido groups through nucleophilic attacking then benzylic migrating. The use of BRSIL was investigated in the analysis of five GCs (creatine, l-arginine, homoarginine, 4-guanidinobutyric acid, and methylguanidine) and two UCs (urea and citrulline). The labeling was found simple and specific. The introduction of bi-phenyl group and the generation of nitrogen heterocyclic ring in the benzil-d0/d5 labeled GCs and UCs improved the retention behaviors in liquid chromatography (LC) and increased the sensitivity of electrospray ionization mass spectrometry (ESI MS) detection. The fragment ion pairs of m/z 182/187 and m/z 210/215 from the benzil-d0/d5 tags facilitated the discovery of potential GCs and UCs candidates residing in biological matrices. The use of BRSIL combined with LC-ESI MS was applied for simultaneously quantitation of GCs and UCs in thyroid tissues. It was demonstrated that nine GCs and UCs were detected, six of which were further quantified based on corresponding standards. It was concluded that five GCs and UCs (l-arginine, homoarginine, 4-guanidinobutyric acid, methylguanidine, and citrulline) were statistically significantly different (p < 0.05) between the para-carcinoma and carcinoma thyroid tissue samples. PMID- 26826697 TI - Multiplex localization of sequential peptide epitopes by use of a planar microbead chip. AB - Epitope mapping is crucial for the characterization of protein-specific antibodies. Commonly, small overlapping peptides are chemically synthesized and immobilized to determine the specific peptide sequence. In this study, we report the use of a fast and inexpensive planar microbead chip for epitope mapping. We developed a generic strategy for expressing recombinant peptide libraries instead of using expensive synthetic peptide libraries. A biotin moiety was introduced in vivo at a defined peptide position using biotin ligase. Peptides in crude Escherichia coli lysate were coupled onto streptavidin-coated microbeads by incubation, thereby avoiding tedious purification procedures. For read-out we used a multiplex planar microbead chip with size- and fluorescence-encoded microbead populations. For epitope mapping, up to 18 populations of peptide loaded microbeads (at least 20 microbeads per peptide) displaying the primary sequence of a protein were analyzed simultaneously. If an epitope was recognized by an antibody, a secondary fluorescence-labeled antibody generated a signal that was quantified, and the mean value of all microbeads in the population was calculated. We mapped the epitopes for rabbit anti-PA28gamma (proteasome activator 28gamma) polyclonal serum, for a murine monoclonal antibody against PA28gamma, and for a murine monoclonal antibody against the hamster polyoma virus major capsid protein VP1 as models. In each case, the identification of one distinct peptide sequence out of up to 18 sequences was possible. Using this approach, an epitope can be mapped multiparametrically within three weeks. PMID- 26826698 TI - Luminescence detection of cysteine based on Ag+-mediated conformational change of terbium ion-promoted G-quadruplex. AB - In this work, we developed a simple and sensitive method for the detection of cysteine (Cys) by employing terbium ion (Tb(3+))-promoted G-qudraplex (G4/Tb) as a luminescent probe, which is based on Ag(+)-mediated conformational change of G4/Tb. Due to Ag(+) is able to compete with Tb(3+) to bind guanine at G4, the presence of Ag(+) can lead to the formation of G4/Tb-Ag(+) complex and disrupt the structure of G4/Tb. Meanwhile, the binding of Ag(+) with G4/Tb will also cause the alteration of the excited state of G4 and more efficient energy transfer from G4 to Tb(3+), enhancing the luminescence of G4/Tb. However, upon the addition of Cys, Ag(+) will be released from G4/Tb-Ag(+) complex because of the high affinity of Cys to Ag(+). This results in the re-formation of the conformation of G4/Tb and the decrease of the luminescence of G4/Tb. So, Ag(+) enhanced luminescence of G4/Tb is associated with its conformational transformation. As a luminescent probe for Cys, G4/Tb not only shows excellent selectivity and sensitivity with a detection limit of 20 nM, but also possesses the features of simple preparation, easy reproducibility, and eliminating the interferences from background fluorescence. We envision that the presented strategy might provide new insight into the biosensing applications of lanthanide complex. PMID- 26826699 TI - Characterization of cetuximab Fc/2 dimers by off-line CZE-MS. AB - Monoclonal antibody (mAb) therapeutics attract the largest concern due to their strong therapeutic potency and specificity. The Fc region of mAbs is common to many new biotherapeutics as biosimilar, antibody drug conjugate or fusion protein. Fc region has consequences for Fc-mediated effector functions that might be desirable for therapeutic applications. As a consequence, there is a continuous need for improvement of analytical methods to enable fast and accurate characterization of biotherapeutics. Capillary zone electrophoresis-Mass spectrometry couplings (CZE-MS) appear really attractive methods for the characterization of biological samples. In this report, we used CZE-MS systems developed in house and native MS infusion to allow precise middle-up characterization of Fc/2 variant of cetuximab. Molecular weights were measured for three Fc/2 charge variants detected in the CZE separation of cetuximab subunits. Two Fc/2 C-terminal lysine variants were identified and separated. As the aim is to understand the presence of three peaks in the CZE separation for two Fc/2 subunits, we developed a strategy using CZE-UV/MALDI-MS and CZE-UV/ESI MS to evaluate the role of N-glycosylation and C-terminal lysine truncation on the CZE separation. The chemical structure of N-glycosylation expressed on the Fc region of cetuximab does not influence CZE separation while C-terminal lysine is significantly influencing separation. In addition, native MS infusion demonstrated the characterization of Fc/2 dimers at pH 5.7 and 6.8 and the first separation of these dimers using CZE-MS. PMID- 26826700 TI - Rapid determination of 135Cs and precise 135Cs/137Cs atomic ratio in environmental samples by single-column chromatography coupled to triple quadrupole inductively coupled plasma-mass spectrometry. AB - For source identification, measurement of (135)Cs/(137)Cs atomic ratio not only provides information apart from the detection of (134)Cs and (137)Cs, but it can also overcome the application limit that measurement of the (134)Cs/(137)Cs ratio has due to the short half-life of (134)Cs (2.06 y). With the recent advancement of ICP-MS, it is necessary to improve the corresponding separation method for rapid and precise (135)Cs/(137)Cs atomic ratio analysis. A novel separation and purification technique was developed for the new generation of triple-quadrupole inductively coupled plasma-mass spectrometry (ICP-MS/MS). The simple chemical separation, incorporating ammonium molybdophosphate selective adsorption of Cs and subsequent single cation-exchange chromatography, removes the majority of isobaric and polyatomic interference elements. Subsequently, the ICP-MS/MS removes residual interference elements and eliminates the peak tailing effect of stable (133)Cs, at m/z 134, 135, and 137. The developed analytical method was successfully applied to measure (135)Cs/(137)Cs atomic ratios and (135)Cs activities in environmental samples (soil and sediment) for radiocesium source identification. PMID- 26826702 TI - A comparison of neuropsychiatric adverse events during early treatment with varenicline or a nicotine patch. AB - AIMS: We compared the risk of mental health episodes requiring hospitalization (primary aim) or out-patient clinic visits (secondary aim) associated with varenicline versus the nicotine patch (NP) in an era prior to psychiatric boxed warnings. DESIGN: Retrospective cohort. SETTING: Department of Veterans Affairs (VA), USA. PARTICIPANTS: VA patients with or without psychiatric comorbidities and a new prescription for varenicline (15 255) were propensity score-matched (1 : 2) to new users of NP (123 054) between 1 May 2006 and 30 September 2007, resulting in 11 774 and 23 548 patients in the varenicline and NP groups, respectively. MEASUREMENTS: The primary outcomes were hospitalizations with a primary discharge diagnosis of a range of mental health disorders: depression, schizophrenia, bipolar disorder, suicide attempt, post-traumatic stress disorder, other psychosis and drug-induced mental disorders. Secondary outcomes were out patient clinic visits with a primary diagnosis of the above list of mental health disorders. FINDINGS: Background characteristics of the treatment groups were similar after matching. There was no statistically significant difference in risk of hospitalization for any of the studied mental health disorders with varenicline compared with NP. Among secondary outcomes there was an increased risk of out-patient clinic visits for schizophrenia among patients who received varenicline [hazard ratio (HR) = 1.27; 95% confidence interval (CI) = 1.07, 1.51], this increase being evident only in those with a pre-existing mental health disorder. CONCLUSION: In US VA patients studied prior to the boxed warning being implemented, use of varenicline for smoking cessation was not associated with a detectable increase compared with nicotine patches in hospitalization for any mental health outcomes. There was an increased rate of out-patient attendances with a primary diagnosis of schizophrenia amounting to five per 100 person years of treatment. This increase was found only in patients with a pre existing mental health disorder. PMID- 26826701 TI - The transcription factor calcium-response factor limits NMDA receptor-dependent transcription in the developing brain. AB - Neuronal activity sculpts brain development by inducing the transcription of genes such as brain-derived neurotrophic factor (Bdnf) that modulate the function of synapses. Sensory experience is transduced into changes in gene transcription via the activation of calcium signaling pathways downstream of both L-type voltage-gated calcium channels (L-VGCCs) and NMDA-type glutamate receptors (NMDARs). These signaling pathways converge on the regulation of transcription factors including calcium-response factor (CaRF). Although CaRF is dispensable for the transcriptional induction of Bdnf following the activation of L-VGCCs, here we show that the loss of CaRF leads to enhanced NMDAR-dependent transcription of Bdnf as well as Arc. We identify the NMDAR subunit-encoding gene Grin3a as a regulatory target of CaRF, and we show that expression of both Carf and Grin3a is depressed by the elevation of intracellular calcium, linking the function of this transcriptional regulatory pathway to neuronal activity. We find that light-dependent activation of Bdnf and Arc transcription is enhanced in the visual cortex of young CaRF knockout mice, suggesting a role for CaRF-dependent dampening of NMDAR-dependent transcription in the developing brain. Finally, we demonstrate that enhanced Bdnf expression in CaRF-lacking neurons increases inhibitory synapse formation. Taken together, these data reveal a novel role for CaRF as an upstream regulator of NMDAR-dependent gene transcription and synapse formation in the developing brain. NMDARs promote brain development by inducing the transcription of genes, including brain-derived neurotrophic factor (BDNF). We show that the transcription factor calcium-response factor (CaRF) limits NMDAR dependent BDNF induction by regulating expression of the NMDAR subunit GluN3A. Loss of CaRF leads to enhanced BDNF-dependent GABAergic synapse formation indicating the importance of this process for brain development. Our observation that both CaRF and GluN3A are down-regulated by intracellular calcium suggests that this may be a mechanism for experience-dependent modulation of synapse formation. PMID- 26826703 TI - The Importance of the Mean Platelet Aggregation Degree in Long-term Dual Antiplatelet Therapy Following Drug-Eluting Stent Implantation. AB - INTRODUCTION: The dual antiplatelet therapy (DAPT) and the response of clopidogrel were two pivotal issues in drug-eluting stent (DES) era. AIMS: To analyze the combined impacts of DAPT and the response to clopidogrel to evaluate their long-term effect on patients undergoing DES implantation. METHODS: Platelet aggregation was serially measured by light transmission aggregometry in all eligible patients during the course of treatment with DAPT, and the mean platelet aggregation degree of each participant was calculated. Based on the duration of DAPT and the mean platelet aggregation degree, all the enrolled patients were then divided into four groups. The primary endpoint was a composite of major adverse cardiovascular events. RESULTS: We analyzed 1245 suitable patients in this study. They were divided into four groups: Group A (12-month DAPT & low platelet aggregation degree) with 233 subjects, Group B (12-month DAPT & high platelet aggregation degree) with 260 subjects, Group C (>12-month DAPT & low platelet aggregation degree) with 374 subjects, and Group D (>12-month DAPT & high platelet aggregation degree) with 378 subjects. Group C was associated with a decreased incidence of primary endpoints [HR 0.512, 95%CI (0.27-0.97); P = 0.040]. The Cox proportional hazard model was further analyzed with Groups A and B combined as the reference category [HR for Group C vs. Group A, 0.84, 95%CI (0.33-2.15); P = 0.719; HR for Group C vs. Group B, 0.45, 95%CI (0.21-0.98); P = 0.043]. Their respective multivariate Cox proportional hazard regressions confirmed these trends. CONCLUSIONS: The mean platelet aggregation degree is of importance in long-term use of DAPT; extension of DAPT beyond 1 year should be implemented cautiously in patients implanted with DESs. PMID- 26826704 TI - Nutrition and lifestyle in healthy aging: the telomerase challenge. AB - Nutrition and lifestyle, known to modulate aging process and age-related diseases, might also affect telomerase activity. Short and dysfunctional telomeres rather than average telomere length are associated with longevity in animal models, and their rescue by telomerase maybe sufficient to restore cell and organismal viability. Improving telomerase activation in stem cells and potentially in other cells by diet and lifestyle interventions may represent an intriguing way to promote health-span in humans. PMID- 26826705 TI - Caries increment in young children in Skaraborg, Sweden: associations with parental sociodemography, health habits, and attitudes. AB - AIM: To explore parental sociodemography, oral health habits, and attitudes in relation to dental caries increment in their children. DESIGN: A longitudinal questionnaire and clinical study. The children were followed annually from age 3 years (n = 271) to 6 years (n = 243). Carious lesions of different depth were registered (initial and manifest) by four calibrated dentists. The parents filled out a questionnaire. Statistics included factor analyses, Cronbach's alpha together with bivariate and multivariate logistic regression analyses. RESULTS: Most of the parents exhibited positive health behaviour and attitudes. 'Late start of toothbrushing of child' was, however, common (>=1 year; 29%) and 'external locus of control' showed a high mean value (10,1; possible range 3-15). In a multivariate model, 'parent born abroad' (OR 3.26, 95% CI 1.85-5.76) and 'parental indulgence' (OR 3.20, 95% CI 1.37-7.51) were the most important for the development of carious lesions in the children. CONCLUSIONS: This study identified 'parent born abroad' and 'parental indulgence' as significant risk factors for caries in the age period 3 to 6 years. Identifying parents with the greatest need should be emphasized, in order to target promotion and prevention activities. PMID- 26826706 TI - Distribution of the c-MYC gene product in colorectal neoplasia. AB - AIMS: Recent attempts to study MYC distribution in human samples have been confounded by a lack of agreement in immunohistochemical staining between antibodies targeting the N-terminus and those targeting the C-terminus of the MYC protein. The aim of this study was to use a novel in-situ hybridization (ISH) approach to detect MYC mRNA in clinically relevant samples, and thereby determine the reliability of MYC-targeting antibodies. METHODS AND RESULTS: We performed immunohistochemistry on human formalin-fixed paraffin embedded normal colon (n = 15), hyperplastic polyp (n = 4) and neoplastic colon samples (n = 55), using the N-terminally directed antibody Y69, and the C-terminally directed antibody 9E10. The MYC protein distributions were then compared with the location of MYC mRNA, determined by ISH. We found that the localization of MYC mRNA correlated well with the protein distribution determined with the N-terminally directed antibody Y69, and was also associated with expression of the proliferation marker Ki67. The protein distribution determined with the C-terminally directed antibody 9E10 was not always associated with MYC mRNA, Y69, or Ki67, and indeed often showed a reciprocal pattern of expression, with staining being strongest in non proliferating cells. CONCLUSIONS: The observed discrepancy between the staining patterns suggests that the significance of 9E10 in immunohistochemical staining is currently uncertain, and therefore should be interpreted with caution. PMID- 26826707 TI - The Effects of Sequence Variation on Genome-wide NRF2 Binding--New Target Genes and Regulatory SNPs. AB - Transcription factor binding specificity is crucial for proper target gene regulation. Motif discovery algorithms identify the main features of the binding patterns, but the accuracy on the lower affinity sites is often poor. Nuclear factor E2-related factor 2 (NRF2) is a ubiquitous redox-activated transcription factor having a key protective role against endogenous and exogenous oxidant and electrophile stress. Herein, we decipher the effects of sequence variation on the DNA binding sequence of NRF2, in order to identify both genome-wide binding sites for NRF2 and disease-associated regulatory SNPs (rSNPs) with drastic effects on NRF2 binding. Interactions between NRF2 and DNA were studied using molecular modelling, and NRF2 chromatin immunoprecipitation-sequence datasets together with protein binding microarray measurements were utilized to study binding sequence variation in detail. The binding model thus generated was used to identify genome wide binding sites for NRF2, and genomic binding sites with rSNPs that have strong effects on NRF2 binding and reside on active regulatory elements in human cells. As a proof of concept, miR-126-3p and -5p were identified as NRF2 target microRNAs, and a rSNP (rs113067944) residing on NRF2 target gene (Ferritin, light polypeptide, FTL) promoter was experimentally verified to decrease NRF2 binding and result in decreased transcriptional activity. PMID- 26826708 TI - Identification of LACTB2, a metallo-beta-lactamase protein, as a human mitochondrial endoribonuclease. AB - Post-transcriptional control of mitochondrial gene expression, including the processing and generation of mature transcripts as well as their degradation, is a key regulatory step in gene expression in human mitochondria. Consequently, identification of the proteins responsible for RNA processing and degradation in this organelle is of great importance. The metallo-beta-lactamase (MBL) is a candidate protein family that includes ribo- and deoxyribonucleases. In this study, we discovered a function for LACTB2, an orphan MBL protein found in mammalian mitochondria. Solving its crystal structure revealed almost perfect alignment of the MBL domain with CPSF73, as well as to other ribonucleases of the MBL superfamily. Recombinant human LACTB2 displayed robust endoribonuclease activity on ssRNA with a preference for cleavage after purine-pyrimidine sequences. Mutational analysis identified an extended RNA-binding site. Knockdown of LACTB2 in cultured cells caused a moderate but significant accumulation of many mitochondrial transcripts, and its overexpression led to the opposite effect. Furthermore, manipulation of LACTB2 expression resulted in cellular morphological deformation and cell death. Together, this study discovered that LACTB2 is an endoribonuclease that is involved in the turnover of mitochondrial RNA, and is essential for mitochondrial function in human cells. PMID- 26826709 TI - Identification of a conserved 5'-dRP lyase activity in bacterial DNA repair ligase D and its potential role in base excision repair. AB - Bacillus subtilis is one of the bacterial members provided with a nonhomologous end joining (NHEJ) system constituted by the DNA-binding Ku homodimer that recruits the ATP-dependent DNA Ligase D (BsuLigD) to the double-stranded DNA breaks (DSBs) ends. BsuLigD has inherent polymerization and ligase activities that allow it to fill the short gaps that can arise after realignment of the broken ends and to seal the resulting nicks, contributing to genome stability during the stationary phase and germination of spores. Here we show that BsuLigD also has an intrinsic 5'-2-deoxyribose-5-phosphate (dRP) lyase activity located at the N-terminal ligase domain that in coordination with the polymerization and ligase activities allows efficient repairing of 2'-deoxyuridine-containing DNA in an in vitro reconstituted Base Excision Repair (BER) reaction. The requirement of a polymerization, a dRP removal and a final sealing step in BER, together with the joint participation of BsuLigD with the spore specific AP endonuclease in conferring spore resistance to ultrahigh vacuum desiccation suggest that BsuLigD could actively participate in this pathway. We demonstrate the presence of the dRP lyase activity also in the homolog protein from the distantly related bacterium Pseudomonas aeruginosa, allowing us to expand our results to other bacterial LigDs. PMID- 26826710 TI - Gene integrated set profile analysis: a context-based approach for inferring biological endpoints. AB - The identification of genes with specific patterns of change (e.g. down-regulated and methylated) as phenotype drivers or samples with similar profiles for a given gene set as drivers of clinical outcome, requires the integration of several genomic data types for which an 'integrate by intersection' (IBI) approach is often applied. In this approach, results from separate analyses of each data type are intersected, which has the limitation of a smaller intersection with more data types. We introduce a new method, GISPA (Gene Integrated Set Profile Analysis) for integrated genomic analysis and its variation, SISPA (Sample Integrated Set Profile Analysis) for defining respective genes and samples with the context of similar, a priori specified molecular profiles. With GISPA, the user defines a molecular profile that is compared among several classes and obtains ranked gene sets that satisfy the profile as drivers of each class. With SISPA, the user defines a gene set that satisfies a profile and obtains sample groups of profile activity. Our results from applying GISPA to human multiple myeloma (MM) cell lines contained genes of known profiles and importance, along with several novel targets, and their further SISPA application to MM coMMpass trial data showed clinical relevance. PMID- 26826712 TI - Suprarenal fixation resulting in intestinal malperfusion after endovascular aortic aneurysm repair. AB - Superior mesenteric artery (SMA) and coeliac axis (CA) occlusion after endovascular abdominal aneurysm aortic repair (EVAR-AAA), using endograft with suprarenal fixation, are uncommon. However, we are reporting a case of visceral malperfusion, which occurred 7 days after successful EVAR with suprarenal fixation for symptomatic AAA. Endograft metal stent barbs caused severe stenosis of SMA and CA. A successful recovery of SMA was carried out by means of a balloon expandable stent released through bare metal stent barbs. We believe that an unfavourable anatomy of a proximal aortic neck and visceral aorta may have caused a wrong stent strut deployment with the coverage of CA and SMA. PMID- 26826711 TI - Natural antisense RNA promotes 3' end processing and maturation of MALAT1 lncRNA. AB - The RNase P-mediated endonucleolytic cleavage plays a crucial role in the 3' end processing and cellular accumulation of MALAT1, a nuclear-retained long noncoding RNA that promotes malignancy. The regulation of this cleavage event is largely undetermined. Here we characterize a broadly expressed natural antisense transcript at the MALAT1 locus, designated as TALAM1, that positively regulates MALAT1 levels by promoting the 3' end cleavage and maturation of MALAT1 RNA. TALAM1 RNA preferentially localizes at the site of transcription, and also interacts with MALAT1 RNA. Depletion of TALAM1 leads to defects in the 3' end cleavage reaction and compromises cellular accumulation of MALAT1. Conversely, overexpression of TALAM1 facilitates the cleavage reaction in trans Interestingly, TALAM1 is also positively regulated by MALAT1 at the level of both transcription and RNA stability. Together, our data demonstrate a novel feed forward positive regulatory loop that is established to maintain the high cellular levels of MALAT1, and also unravel the existence of sense-antisense mediated regulatory mechanism for cellular lncRNAs that display RNase P-mediated 3' end processing. PMID- 26826713 TI - Cardiac surgery for infective endocarditis in patients with intravenous drug use. AB - OBJECTIVES: Intravenous drug users have a high risk of infective endocarditis and reduced survival. Cardiac surgery may be recommended for these patients, but redo surgery is controversial. This study describes the characteristics and outcomes of intravenous drug users accepted for surgery during a 12-year period. METHODS: This retrospective study included 29 injecting drug users treated with valve surgery for endocarditis between January 2001 and December 2013 at a tertiary academic centre. Survival was assessed by Kaplan-Meier analysis. RESULTS: The median patient age was 36 (24-63) years and 27 patients (93%) were male. Staphylococcus aureus (52%) and Enterococcus faecalis (17%) were the most common microorganisms. Common illicit drugs were opioids (69%), amphetamines (52%) and benzodiazepines (24%). Mixed abuse was reported in 66% of patients. Seven patients (24%) had prior intracardial implants or native valve pathology. Twenty five patients (86%) were positive for hepatitis C virus antibody, but none carried the human immunodeficiency virus. Twelve (41%) were homeless and 15 (52%) had poor dental hygiene. Three patients (10%) received medication-assisted rehabilitation before surgery. The main indications for surgery were regurgitation and secondary heart failure (86%), embolization (41%) and uncontrolled infection (24%). Aortic valve replacement was performed in 24 patients (83%), either as part of univalvular or multiple valve surgery. Seven patients (24%) had multivalvular endocarditis. All but 3 patients received biological valve prostheses. The 30-day mortality was 7% after first time surgery. During follow-up, 15 patients (52%) presented with reinfection: 10 (35%) were offered a second and 2 (7%) a third operation. Thirty-day mortality was 10% after redo surgery. Thirteen patients (45%) died within a median of 22 (0-84) months. Continued intravenous drug use was reported in 70 and 44% of patients after the first and second operation, respectively. CONCLUSIONS: Cardiac surgery for infective endocarditis has acceptable early postoperative results among intravenous drug users. The 2- and 5-year survival were 79 and 59%, respectively. The number of reinfections was high within 2 years, as continued drug use seems to be a major challenge for this group. PMID- 26826714 TI - Preoperative planning of left-sided valve surgery with 3D computed tomography reconstruction models: sternotomy or a minimally invasive approach? AB - OBJECTIVES: With the emergence of a new concept aimed at individualization of patient care, the focus will shift from whether a minimally invasive procedure is better than conventional treatment, to the question of which patients will benefit most from which technique? The superiority of minimally invasive valve surgery (MIVS) has not yet been proved. We believe that through better patient selection advantages of this technique can become more pronounced. In our current study, we evaluate the feasibility of 3D computed tomography (CT) imaging reconstruction in the preoperative planning of patients referred for MIVS. METHODS: We retrospectively analysed all consecutive patients who were referred for minimally invasive mitral valve surgery (MIMVS) and minimally invasive aortic valve replacement (MIAVR) to a single surgeon in a tertiary referral centre for MIVS between March 2014 and 2015. Prospective preoperative planning was done for all patients and was based on evaluations by a multidisciplinary heart-team, an echocardiography, conventional CT images and 3D CT reconstruction models. RESULTS: A total of 39 patients were included in our study; 16 for mitral valve surgery (MVS) and 23 patients for aortic valve replacement (AVR). Eleven patients (69%) within the MVS group underwent MIMVS. Five patients (31%) underwent conventional MVS. Findings leading to exclusion for MIMVS were a tortuous or slender femoro-iliac tract, calcification of the aortic bifurcation, aortic elongation and pericardial calcifications. Furthermore, 2 patients had a change of operative strategy based on preoperative planning. Seventeen (74%) patients in the AVR group underwent MIAVR. Six patients (26%) underwent conventional AVR. Indications for conventional AVR instead of MIAVR were an elongated ascending aorta, ascending aortic calcification and ascending aortic dilatation. One patient (6%) in the MIAVR group was converted to a sternotomy due to excessive intraoperative bleeding. Two mortalities were reported during conventional MVS. There were no mortalities reported in the MIMVS, MIAVR or conventional AVR group. CONCLUSIONS: Preoperative planning of minimally invasive left-sided valve surgery with 3D CT reconstruction models is a useful and feasible method to determine operative strategy and exclude patients ineligible for a minimally invasive approach, thus potentially preventing complications. PMID- 26826715 TI - Routine operation theatre extubation after cardiac surgery in the elderly. AB - OBJECTIVES: The aim was to analyse in-hospital outcomes of patients over 70 years of age undergoing routine immediate operation theatre (OT) extubation after on pump or off-pump cardiac surgery. METHODS: A retrospective analysis was performed of prospectively collected data over a 4-year period (2011-14) from elderly patients undergoing early extubation after cardiac surgery at a single institution. All patients over 70 years were considered eligible for immediate OT or intensive care unit (ICU) early extubation after meeting specific criteria. All types of non-emergency cardiac surgery were included. Cardiac surgical risk stratification was assessed with EuroSCORE II and age, creatinine level and left ventricular ejection fraction (ACEF) score. RESULTS: Among the 415 patients operated on during the period, 275 (66.3%) were >=70 years old. One hundred and forty patients (50.9%) of the elderly group were extubated successfully in the OT. Excluding off-pump coronary surgery, OT extubation was achieved in 51.5% of cases. The rate of risk of reintubation within 24 h of surgery after OT extubation was 2.1%. The in-hospital mortality rate was 4.7%, and the complication rate was 11.6%, independently of extubation timing. Elderly patients extubated in the OT had a significantly lower median EuroSCORE II risk level and ACEF score, more isolated valve surgeries, reduced cardiopulmonary bypass time, less complications and shorter length of stay than ICU-extubated patients. In the multivariate analysis, only the ACEF score remained as an independent variable associated with OT extubation in the elderly (odds ratio 25.0, 95% CI 2.74-228.8, P = 0.004), and had good discriminating power [receiver operating characteristics (ROC) area 0.713]. On the other hand, the EuroSCORE ROC area used to predict OT extubation was 0.694, and the cut-off analysis showed that a risk value under 2.11 was associated with 72.1% OT extubation versus 37.3% when the risk value was over 2.11 (P = 0.0002). CONCLUSIONS: OT extubation in the elderly can be safely performed in nearly 50% of patients, without apparently worsening their outcomes. A key point of this success was the use of a short-acting volatile agent to maintain anaesthesia throughout the procedure. Low- or moderate-risk cardiac surgery assessed with a preoperative EuroSCORE II <2.11 will help to better predict successful OT extubation in the elderly. PMID- 26826716 TI - FastLSU: a more practical approach for the Benjamini-Hochberg FDR controlling procedure for huge-scale testing problems. AB - MOTIVATION: We address a common problem in large-scale data analysis, and especially the field of genetics, the huge-scale testing problem, where millions to billions of hypotheses are tested together creating a computational challenge to control the inflation of the false discovery rate. As a solution we propose an alternative algorithm for the famous Linear Step Up procedure of Benjamini and Hochberg. RESULTS: Our algorithm requires linear time and does not require any P value ordering. It permits separating huge-scale testing problems arbitrarily into computationally feasible sets or chunks Results from the chunks are combined by our algorithm to produce the same results as the controlling procedure on the entire set of tests, thus controlling the global false discovery rate even when P values are arbitrarily divided. The practical memory usage may also be determined arbitrarily by the size of available memory. AVAILABILITY AND IMPLEMENTATION: R code is provided in the supplementary material. CONTACT: sbatista@cs.princeton.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26826717 TI - Library of binding protein scaffolds (LibBP): a computational platform for selection of binding protein scaffolds. AB - MOTIVATION: Developments in biotechnology have enabled the in vitro evolution of binding proteins. The emerging limitations of antibodies in binding protein engineering have led to suggestions for other proteins as alternative binding protein scaffolds. Most of these proteins were selected based on human intuition rather than systematic analysis of the available data. To improve this strategy, we developed a computational framework for finding desirable binding protein scaffolds by utilizing protein structure and sequence information. RESULTS: For each protein, its structure and the sequences of evolutionarily-related proteins were analyzed, and spatially contiguous regions composed of highly variable residues were identified. A large number of proteins have these regions, but leucine rich repeats (LRRs), histidine kinase domains and immunoglobulin domains are predominant among them. The candidates suggested as new binding protein scaffolds include histidine kinase, LRR, titin and pentapeptide repeat protein. AVAILABILITY AND IMPLEMENTATION: The database and web-service are accessible via http://bcbl.kaist.ac.kr/LibBP CONTACT: kds@kaist.ac.krSupplementary data: Supplementary data are available at Bioinformatics online. PMID- 26826718 TI - BCFtools/RoH: a hidden Markov model approach for detecting autozygosity from next generation sequencing data. AB - Runs of homozygosity (RoHs) are genomic stretches of a diploid genome that show identical alleles on both chromosomes. Longer RoHs are unlikely to have arisen by chance but are likely to denote autozygosity, whereby both copies of the genome descend from the same recent ancestor. Early tools to detect RoH used genotype array data, but substantially more information is available from sequencing data. Here, we present and evaluate BCFtools/RoH, an extension to the BCFtools software package, that detects regions of autozygosity in sequencing data, in particular exome data, using a hidden Markov model. By applying it to simulated data and real data from the 1000 Genomes Project we estimate its accuracy and show that it has higher sensitivity and specificity than existing methods under a range of sequencing error rates and levels of autozygosity. AVAILABILITY AND IMPLEMENTATION: BCFtools/RoH and its associated binary/source files are freely available from https://github.com/samtools/BCFtools CONTACT: vn2@sanger.ac.uk or pd3@sanger.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26826719 TI - Skin problems and EGFR-tyrosine kinase inhibitor. AB - Epidermal growth factor receptor inhibition is a good target for the treatment of lung, colon, pancreatic and head and neck cancers. Epidermal growth factor receptor-tyrosine kinase inhibitor was first approved for the treatment of advanced lung cancer in 2002. Epidermal growth factor receptor-tyrosine kinase inhibitor plays an essential role in the treatment of cancer, especially for patients harbouring epidermal growth factor receptor activating mutation. Hence, skin toxicity is the most concerning issue for the epidermal growth factor receptor-tyrosine kinase inhibitor treatment. Skin toxicity is bothersome and sometimes affects the quality of life and treatment compliance. Thus, it is important for physicians to understand the background and how to manage epidermal growth factor receptor-tyrosine kinase inhibitor-associated skin toxicity. Here, the author reviewed the mechanism and upfront preventive and reactive treatments for epidermal growth factor receptor inhibitor-associated skin toxicities. PMID- 26826720 TI - Practical patterns for stereotactic body radiotherapy to hepatocellular carcinoma in Korea: a survey of the Korean Stereotactic Radiosurgery Group. AB - OBJECTIVE: To investigate practical patterns for stereotactic body radiotherapy to hepatocellular carcinoma in Korea. METHODS: In June 2013, the Korean Stereotactic Radiosurgery Group of the Korean Society for Radiation Oncology conducted a national patterns-of-care survey about stereotactic body radiotherapy to the liver lesion in hepatocellular carcinoma, consisting of 19 questions and 2 clinical scenarios. RESULTS: All 208 radiation oncologists (100%), who are regular members of Korean Society for Radiation Oncology, responded to this survey. Among these, 95 radiation oncologists were specialists for hepatology; 64 physicians did not use stereotactic body radiotherapy for hepatocellular carcinoma, and 31 physicians used stereotactic body radiotherapy. Most physicians (52%) performed stereotactic body radiotherapy to hepatocellular carcinoma in <=5 cases per year. Physicians applied stereotactic body radiotherapy according to tumour size and baseline Child-Pugh class. All physicians agreed the use of stereotactic body radiotherapy to 2.8-cm hepatocellular carcinoma with Child-Pugh class of A, while 23 physicians (74%) selected stereotactic body radiotherapy for Child-Pugh class of B. Nineteen physicians (61%) selected stereotactic body radiotherapy to 5-cm hepatocellular carcinoma with Child-Pugh class of A, and only 14 physicians (45%) selected stereotactic body radiotherapy for Child-Pugh class of B. On the other hand, the preferred dose scheme was same as 60 Gy in three fractions. CONCLUSIONS: Among radiation oncologists in Korea, there was diversity in the practice for stereotactic body radiotherapy to the liver lesion in hepatocellular carcinoma. Additional prospective studies are necessary to standardize the practice and establish Korea-specific practice guidelines for hepatocellular carcinoma stereotactic body radiotherapy. PMID- 26826721 TI - Retrospective analysis of the clinical efficacy of definitive chemoradiotherapy for patients with hypopharyngeal cancer. AB - OBJECTIVE: A retrospective analysis was performed to evaluate the clinical efficacy of definitive chemoradiotherapy including intensity-modulated radiotherapy for patients with hypopharyngeal cancer. METHODS: Previously untreated 204 patients with hypopharyngeal cancer were treated with definitive chemoradiotherapy. Of note, 66-70 Gy was delivered to the primary and involved nodes and 36-54 Gy was delivered to the prophylactic lymph node using standard fractionated radiotherapy. One hundred and forty-six patients received induction chemotherapy as a larynx preservation strategy, followed by definitive radiotherapy with or without concurrent chemotherapy. Intensity-modulated radiotherapy was also performed after 2006. RESULTS: The median follow-up time of this cohort was 43.4 months (range; 6.9-151.0). The 3-year overall survival, progression-free survival and larynx preservation survival rates were 78.8% (95% confidence interval; 73.0-85.0), 58.4% (95% confidence interval; 51.8-65.9) and 67.5% (95% confidence interval; 61.0-74.7), respectively. Multivariate analyses identified the following significant prognostic factors: an advanced age, the T category and N category for overall survival, the T category and N category for progression-free survival and the T category for larynx preservation survival. Acute toxicities of Grade 3 or higher were observed in 47 patients (23.0%). Two patients (1.0%) had Grade 4 pharyngeal edema. Suspicious treatment-related death due to lethal pharyngeal hemorrhage occurred in 1 (0.4%) patient. The rates of Grade 2 xerostomia in patients treated with intensity-modulated radiotherapy were 28.1, 17.4 and 9.5% at 6 months, 1 and 2 years after the completion of radiotherapy, respectively. CONCLUSIONS: The efficacy and safety of definitive chemoradiotherapy are considered feasible with sufficient laryngeal preservation. PMID- 26826722 TI - Patient complaints about hospital services: applying a complaint taxonomy to analyse and respond to complaints. AB - OBJECTIVE: To explore the applicability of a patient complaint taxonomy to data on serious complaint cases. DESIGN: Qualitative descriptive study. SETTING: Complaints made to the New South Wales (NSW) Health Care Complaints Commission, Australia between 2005 and 2010. PARTICIPANTS: All 138 cases of serious complaints by patients about public hospitals and other health facilities investigated in the 5-year period. MAIN OUTCOME MEASURE: A thematic analysis of the complaints was conducted to identify particular complaint issues and the Reader et al. (Patient complaints in healthcare systems: a systematic review and coding taxonomy. BMJ Qual Saf 2014;23:678-89.) patient complaint taxonomy was then used to classify these issues into categories and sub-categories. RESULTS: The 138 investigated cases revealed 223 complaint issues. Complaint issues were distributed into the three domains of the patient complaint taxonomy: clinical, management and relationships. Complaint issue most commonly related to delayed diagnosis, misdiagnosis, medication errors, inadequate examinations, inadequate/nil treatment and quality of care including nursing care. CONCLUSIONS: The types of complaints from patients about their healthcare investigated by the NSW Commission were similar to those received by other patient complaint entities in Australia and worldwide. The application of a standard taxonomy to large numbers of complaints cases from different sources would enable the creation of aggregated data. Such data would have better statistical capacity to identify common safety and quality healthcare problems and so point to important areas for improvement. Some conceptual challenges in devising and using a taxonomy must be addressed, such as inherent problems in ensuring coding consistency, and giving greater weight to patient concerns about their treatment. PMID- 26826723 TI - Sensitivities of Two Zebrafish TRPA1 Paralogs to Chemical and Thermal Stimuli Analyzed in Heterologous Expression Systems. AB - Transient receptor potential A1 (TRPA1) is the only member of the mouse, chick, and frog TRPA family, whereas 2 paralogs (zTRPA1a and zTRPA1b) are present in zebrafish. We herein investigated functional differences in the 2 zebrafish TRPA1s. HEK293T cells were used as heterologous expression systems, and the sensitivities of these cells to 4 chemical irritants (allyl isothiocyanate [AITC], caffeine, auto-oxidized epigallocatechin gallate [EGCG], and hydrogen peroxide [H2O2]) were compared with Ca(2+) imaging techniques. Sensitivities to the activators for AITC, oxidized EGCG, and H2O2 were higher in cells expressing zTRPA1a than in those expressing zTRPA1b, whereas caffeine appeared to activate both cells equally. We also characterized the thermal sensitivity of Xenopus oocytes expressing each TRPA1 electrophysiologically using a 2-electrode voltage clamp. Although endogenous currents induced by a cold stimulation were observed in control oocytes in some batches, oocytes expressing zTRPA1b showed significantly stronger cold- and heat-induced responses. However, significant thermal activation was not observed in oocytes expressing zTRPA1a. The results obtained using in vitro expression systems suggest that zTRPA1a is specialized for chemical sensing, whereas zTRPA1b responds to thermal stimuli. Furthermore, characterization of the chimeric molecule of TRPA1a and 1b revealed the importance of the N-terminal region in chemical and thermal sensing by zTRPA1s. PMID- 26826724 TI - CORRECTION. Arabidopsis RGLG2, Functioning as a RING E3 Ligase, Interacts with AtERF53 and Negatively Regulates the Plant Drought Stress Response. PMID- 26826725 TI - CORRECTION. G-Box Binding Factor1 Reduces CATALASE2 Expression and Regulates the Onset of Leaf Senescence in Arabidopsis. PMID- 26826726 TI - CORRECTION. A G-Box-Like Motif Is Necessary for Transcriptional Regulation by Circadian Pseudo-Response Regulators in Arabidopsis. PMID- 26826728 TI - The timing of cranioplasty affect mean operative time and postoperative subdural fluid collection. PMID- 26826729 TI - A simulation study of the effects of alcohol on driving performance in a Chinese population. AB - Driving under the influence of alcohol (DUIA) is a significant factor contributing to road traffic crashes, injuries, and fatalities. Although the effects of alcohol on driving performance are widely acknowledged, studies of the effects of alcohol impairment on driving performance and particularly on the control system of Chinese adults are rare. This study attempts to evaluate the effects of alcohol on the driving performance of Chinese adults using a driving simulator. METHOD: A double-blind experimental study was conducted to evaluate the effects of alcohol impairment on the driving performance of 52 Chinese participants using a driving simulator. A series of simulated driving tests covering two driving modules, including emergency braking (EB) and following braking (FB), at 50km/h and 80km/h were performed. Linear mixed models were established to evaluate driving performance in terms of braking reaction time (BRT), the standard deviation of lateral position (SD-LANE), and the standard deviation of speed (SD-SPEED). RESULTS: Driving performance in terms of BRT and SD-LANE was highly correlated with the level of alcohol consumption, with a one unit increase in breath alcohol concentration (BrAC) degrading BRT and SD-LANE by 0.3% and 0.2%, respectively. Frequent drinkers generally reacted faster in their BRT than less-frequent drinkers and non-drinkers by 10.2% and 30.6%, respectively. Moreover, alcohol impairment had varying effects on certain aspects of the human control system, and automatic action was less likely to be affected than voluntary action from a psychological viewpoint. CONCLUSION: The findings should be useful for planning and developing effective measures to combat drink driving in Chinese communities. PMID- 26826730 TI - Framing Samuel See: the discursive detritus of the moral panic over the "double epidemic" of methamphetamines and HIV among gay men. AB - After being arrested for violating a restraining order against his husband, on November 24, 2013, Yale professor Samuel See died while in lockup at the Union Avenue Detention Center in New Haven, Connecticut. The death received media attention around the world, with readers arguing online about whether See's death was caused by police misconduct, as his friends and colleagues charged in interviews and during a well-publicised march and protest. When an autopsy revealed that he had died from a methamphetamine-induced heart attack, online commentary changed dramatically, with See's many supporters rhetorically abandoning him and others describing him as a stereotype of the gay meth addict who deserved his fate. In this article, I argue that this shift in the interpretation and meaning of See's death can be traced to the discursive structures left by the moral panic about crystal meth in the United States (1996 2008), which comprised within it a secondary moral panic about crystal meth in the gay community and its connection to the spread of HIV and a possible super strain (2005-2008). PMID- 26826731 TI - Identification and characterization of potent, selective and metabolically stable IKKbeta inhibitor. AB - We have previously reported the identification of a rhodanine compound (1) with well-balanced inhibitory activity against IKKbeta and collagen-induced TNFalpha activated cells. However, we need more optimized compounds because of its instability over plasma and microsome. As part of a program directed toward the optimization of IKKbeta inhibitor, we modified a substituent of parent compound to a series of functional groups. Among substituted compounds, fluorine substituent (12) on the para position of phenyl ring restored the stability toward plasma and microsome while retaining inhibitory potency and selectivity against IKKbeta over other kinases. Also, we have demonstrated that compound 12 is an ATP non-competitive inhibitor and safe enough to apply to animal experiment from an acute toxicity test. PMID- 26826732 TI - Pyridoxine hydroxamic acids as novel HIV-integrase inhibitors. AB - A series of pyridoxine hydroxamic acid analog bearing a 5-aryl-spacers were synthesized. Evaluation of these novel HIV integrase complex inhibitors revealed compounds with high potency against wild-type HIV virus. PMID- 26826733 TI - Lanostane-type triterpenes from the fungal endophyte Scleroderma UFSMSc1 (Persoon) Fries. AB - Two lanostane triterpenoids (sclerodols A and B) were isolated from the culture of the Eucalyptus grandis derived from the endophyte Scleroderma UFSM Sc1(Persoon) Fries together with three known compounds: one related triterpenoid lanosta-8,23-dien-3beta,25-diol, the disaccharide alpha,beta-trehalose, and the sugar alcohol mannitol. Their structures were elucidated on the basis of 2D NMR, HRME, and single-crystal X-ray diffraction data. The methanol crude extract and the isolated lanostane triterpenoids showed promising anticandidal activities. PMID- 26826734 TI - Computer-aided design of negative allosteric modulators of metabotropic glutamate receptor 5 (mGluR5): Comparative molecular field analysis of aryl ether derivatives. AB - The metabotropic glutamate receptors (mGlu receptors) have emerged as attractive targets for number of neurological and psychiatric disorders. Recently, mGluR5 negative allosteric modulators (NAMs) have gained considerable attention in pharmacological research. Comparative molecular field analysis (CoMFA) was performed on 73 analogs of aryl ether which were reported as mGluR5 NAMs. The study produced a statistically significant model with high correlation coefficient and good predictive abilities. PMID- 26826735 TI - Heterosexual female adolescents' decision-making about sexual intercourse and pregnancy in rural Ontario, Canada. AB - INTRODUCTION: Rural female adolescents experience unique circumstances to sexual health care and information as compared to urban adolescents. These circumstances are largely due to their more isolated geographical location and rural sociocultural factors. These circumstances may be contributing factors to an incidence of adolescent pregnancy that is higher in rural areas than in urban cities. Thus, this higher incidence of pregnancy may be due to the ways in which rural adolescents make decisions regarding engagement in sexual intercourse. However, the rural female adolescent sexual decision-making process has rarely, if ever, been studied, and further investigation of this process is necessary. Focusing on rural female adolescents aged 16-19 years is especially significant as this age range is used for reporting most pregnancy and birth statistics in Ontario. METHODS: Charmaz's guidelines for a constructivist grounded theory methodology were used to gain an in-depth understanding of eight Ontario rural female adolescents' decision-making process regarding sexual intercourse and pregnancy, and how they viewed rural factors and circumstances influencing this process. Research participants were obtained through initial sampling (from criteria developed prior to the study) and theoretical sampling (by collecting data that better inform the categories emerging from the data). Eight participants, aged 16-19 years, were invited to each take part in 1-2-hour individual interviews, and four of these participants were interviewed a second time to verify and elaborate on emerging constructed concepts, conceptual relationships, and the developing process. Data collection and analysis included both field notes and individual interviews in person and over the telephone. Data were analyzed for emerging themes to construct a theory to understand the participants' experiences making sexual decisions in a rural environment. RESULTS: The adolescent sexual decision-making process, Prioritizing Influences, that emerged from the analysis was a complex and non-linear process that involved prioritizing four influences within the rural context. The influences that participants of this study described as being part of their sexual decision making process were personal values and circumstances, family values and expectations, friends' influences, and community influences. When influences coincided, they strengthened participants' sexual decisions, whereas when influences opposed each other, participants felt conflicted and prioritized the influence that had the most effect on their personal lives and future goals. Although these influences may be common to all adolescents, they impact the rural female adolescent sexual decision-making process by influencing and being influenced by geographical and sociocultural factors that make up the rural context. CONCLUSIONS: This study reveals important new and preliminary information about rural female adolescents' sexual decision-making process and factors that affect it. Findings improve understanding of how rural female adolescents make choices regarding sexual intercourse and pregnancy and can be used to guide future research projects that could facilitate effective development of sexual health promotion initiatives, inform rural health policy and practices, and enhance existing sexual education programs in rural communities. PMID- 26826736 TI - Champions' perspectives on implementing the National Lesbian, Gay, Bisexual, Transgender and Intersex Ageing and Aged Care Strategy in Queensland. AB - Objective The National Lesbian, Gay, Bisexual, Transgender and Intersex (LGBTI) Ageing and Aged Care Strategy was introduced by the Commonwealth Government in 2012. The present study explored perceptions of the first Aged Care Champions (trained employees) of the opportunities, challenges and barriers to implementing the Strategy in Queensland. Methods The present study was an exploratory study of Champions who were nominated by their providers to build capacity around the Strategy for introduction into their organisations. The Champions (n = 62) were surveyed before commencing their training programs. Quantitative and qualitative material was collected on how the Champions perceived the introduction of the six standards within their organisation. Results Champions perceived that there were opportunities to improve inclusivity, leverage organisational support and increase training and support to staff. Key challenges identified were internal attitudes and values, a lack of resources and a need for training and networking. Significant barriers included a lack of management support, resistant staff and pre-existing prejudicial values. Conclusions Providers and practitioners can leverage the opportunity to increase organisational levels of inclusivity, demonstrate organisational support to improve outcomes for clients and stakeholders and, importantly, provide staff training and development critical to the successful implementation of the Strategy. What is known about the topic? Many LGBTI elders have faced a lived history of oppression and discrimination and have special health care needs. As they age, their needs for greater levels of care increase, but for many so to do their concerns about receiving equitable treatment. What does this paper add? The National LGBTI Ageing and Aged Care Strategy was introduced to address the concerns and needs of LGBTI elders and ensure inclusive and supportive care. This study explores the opportunities, challenges and barriers as perceived by employees trained to introduce the Strategy into their services in Queensland. The present study is the first to explore the introduction of the Strategy from employees' perspectives. What are the implications for practitioners? In the present study, the opportunity for increasing inclusivity, levels of support and training and development were explored from an employee perspective, giving voice to this group of practitioners. Challenges, including current attitudes and values of staff and management, as well as a lack of resources and making connections and networks, are identified. Finally, barriers to the implementation of the Strategy are outlined, including levels of support, staff resistance, values and past negative histories of many LGBTI elders. PMID- 26826737 TI - [Neumococcal vaccine: "the road to progress is neither fast nor easy"]. PMID- 26826738 TI - [Leser-Trelat sign associated with pancreatic cancer]. PMID- 26826739 TI - [Infant acute leukemia]. AB - If acute leukemia is the most frequent cancer in childhood (33%), it remains a very rare diagnosis in infants less than one year old, e.g. less than 5% of cases. At this age, the frequency of acute lymphoblastic leukemia (ALL) (almost all of B-lineage) is quite similar to the one of myeloblastic forms (AML). Infant leukemia frequently presents with high hyperleucocytosis, major tumoral burden and numerous extra-hematological features, especially in central nervous system and skin. Whatever the lineage, the leukemic cell is often very immature cytologically and immunologically. Rearrangements of the Mixed Lineage Leukemia (MLL) gene, located on band 11q23, are the hallmark of these immature leukemias and confer a particular resistance to conventional approaches, corticosteroids and chemotherapy. The immaturity of infants less than 1-year-old is associated to a decrease of the tolerable dose-intensity of some drugs (anthracyclines, alkylating agents) or asks questions about some procedures like radiotherapy or high dose conditioning regimen, responsible of inacceptable acute and late toxicities. The high level of severe infectious diseases and other high-grade side effects limits also the capacity to cure these infants. The survival of infants less than 1-year-old with AML is only 50% but similar to older children. On the other hand, survival of those with ALL is the same, then quite limited comparing the 80% survival in children over one year. Allogeneic stem cell transplantations are indicated in high-risk subgroups of infant ALL (age below 6 months, high hyperleucocytosis >300.10(9)/L, MLL-rearrangement, initial poor prednisone response). However, morbidity and mortality remain very important and these approaches cannot be extended to all cases. During the neonatal period, the dismal prognosis linked to the high number of primary failures or very early relapses and uncertainties about the late toxicities question physicians about ethics. It is an emergency to propose different strategies (targeted therapies) to these infants with acute leukemia as conventional trials failed to improve outcome. PMID- 26826740 TI - Metabolite profiles of essential oils and molecular markers analysis to explore the biodiversity of Ferula communis: Towards conservation of the endemic giant fennel. AB - Giant fennel (Ferula communis L.) is well known in folk medicine for the treatment of various organ disorders. The biological importance of members of genus Ferula prompted us to investigate the leaves of the endangered Tunisian medicinal plant F. communis L. not previously investigated. An estimate of genetic diversity and differentiation between genotypes of breeding germplasm is of key importance for its improvement. Thus, four F. communis populations were RAPD fingerprinted (63 RAPD markers generated by 7 primers) and the composition of their leaf essential oils (EO) (134 EO compounds) was characterized by GC-MS. Cluster analysis based on the leaf volatiles chemical composition of F. communis accessions defined three chemotypes according to main compounds have been distinguished: alpha-eudesmol/beta-eudesmol/gamma-terpinene; alpha-eudesmol/alpha pinene/caryophyllene oxide and chamazulene/alpha-humulene chemotypes. A high genetic diversity within population and high genetic differentiation among them, based on RAPDs, were revealed (H(pop)=0.320 and GST=0.288) caused both by the habitat fragmentation, the low size of most populations and the low level of gene flow among them. The RAPD dendrogram showed separation of three groups. Populations dominated by individuals from the beta-eudesmol/gamma-terpinene; chemotype showed the lowest gene diversity (H=0.104), while populations with exclusively alpha-pinene/caryophyllene oxide chemotype showed the highest value (H=0.285). The UPGMA dendrogram and PCA analysis based on volatiles yielded higher separation among populations, indicated specific adaptation of populations to the local environments. Correlation analysis showed a non-significant association between the distance matrices based on the genetic markers (RAPD) and chemical compounds of essential oil (P>0.05) indicating no influence of genetic background on the observed chemical profiles. These results reinforce the use of both volatile compounds and RAPD markers as a starting point for in situ conservation. The analysis of chemical constitution of oil of the populations from a specific region revealed predominance of specific constituents indicating possibility of their collection/selection for specific end uses like phytomedicines. Sufficient molecular and biochemical diversity detected among natural populations of this species will form the basis for the future improvement. The correlation between matrices of RAPD and essential oils was not significant. The conservation strategies of populations should be made according to their level of genetic and chemical diversity in relation to geographic location of populations. Our results give some insights into the characterization of this as yet little investigated plant. PMID- 26826741 TI - [Serious ocular trauma in children: Retrospective study of 74 cases]. PMID- 26826742 TI - [Non-traumatic vitreous hemorrhage]. AB - Spontaneous vitreous hemorrhage is a serious disease whose incidence is 7 per 100,000 people per year. Posterior vitreous detachment with or without retinal tear, diabetic retinopathy, vascular proliferation after retinal vein occlusion, age-related macular degeneration and Terson's syndrome are the most common causes. Repeated ultrasonography may ignore a retinal tear or detachment and delay vitrectomy that is the only treatment for serious forms. The occurrence of retinal tear or detachment is a surgical emergency as well as rubeosis or diabetic tractional retinal detachment involving the macula. Intravitreal injection of antiangiogenic agents are helpful in clearing the vitreous cavity, facilitating laser photocoagulation and reducing the risks of bleeding during preretinal neovascular membranes dissection. PMID- 26826743 TI - [Management of eyelid carcinomas: Retrospective bicentric study of 64 cases and review of the literature]. AB - PURPOSE: To study the epidemiologic, clinical and histological aspects of eyelid carcinomas in our context, and to evaluate our surgical management on an oncological, functional and aesthetic level. PATIENTS AND METHODS: This work is a retrospective bicentric study extended over a 5-year period between January 2009 and December 2013, including 64 patients with eyelid carcinoma undergoing surgery in the Plastic and Reconstructive Surgery Department at the Avicenne University Hospital of Rabat and in the ENT/Head and Neck Surgery Department at the Hassan II University Hospital of Fez. RESULTS: The study included 25 men and 39 women with a mean age of 60.6 +/- 15.33 years. Advanced age and chronic sun exposure were the most important risk factors. The most commonly involved site was the lower eyelid (53%). Histological examination emphasized the very high prevalence of basal cell carcinoma (90.62%). Surgical treatment was performed in all our patients followed by an extemporaneous and/or standard histological examination of the surgical specimen. Exenteration was performed in one patient with adjuvant radiation therapy. Reconstruction incorporated a variety of techniques, of which total skin graft and Mustarde flap were the most common in our series. Aside from a few complications, the postoperative results were satisfactory for the majority of our patients. CONCLUSION: Malignant tumors of the eyelids, of which basal cell carcinoma is the most common, pose a therapeutic problem where surgery remains the most utilized treatment option. The best treatment is prevention and diagnosis of early lesions to improve prognosis and to avoid worse outcomes. PMID- 26826744 TI - [Excimer laser-assisted lamellar endothelial keratoplasty (ExALEK): Technique and results]. AB - INTRODUCTION: The purpose of this study is to describe a technique for thin endothelial lamellar keratoplasty and to present the results for endothelial transplant performed at the University Hospital of Nantes. MATERIALS AND METHODS: This paper is a retrospective, single-center descriptive study conducted at the University Hospital of Nantes from September 2010 to May 2014, at first for anatomical or analgesic indications (group 1) and then extended to visual indications (group 2). Patients were followed for 12 months. The preparation of the endothelial graft includes an excimer-laser ablation of the residual stromal bed after lamellar keratectomy by manual deep anterior approach. RESULTS: Seventy surgeries were analyzed. The etiologies were mainly Fuchs Dystrophy, secondary endothelial dystrophy and post-penetrating keratoplasty endothelial failure. Fifty-three patients were integrated in group 1 and seventeen patients in group 2. In group 1, the mean VA at 12 months was 0.70 +/- 0.30 Log MAR (0.2 decimal equivalent). In group 2, the mean VA at 12 months was 0.28 +/- 0.12 Log MAR (0.5 decimal equivalent). Pachymetry decreased from 740 +/- 125.1 MUm preoperatively to 613.4 +/- 73.4 MUm at 12 months. The average central thickness of the graft was 84.1 +/- 28.9 MUm at 1 month and 80.2 +/- 29.4 MUm at 12 months. CONCLUSION: The advantage of this new surgical technique is that it is a rapid and repeatable method allowing thin grafts with satisfactory functionality and easy handling. Its performance independent of the scheduled surgery, allows for predictable organization in the operating room. PMID- 26826745 TI - "Candle wax dripping" lesions in ocular sarcoidosis. PMID- 26826746 TI - Nasolacrimal duct office probing in children under the age of 12 months: Cure rate and cost evaluation. AB - INTRODUCTION: Controversy exists regarding the treatment of infants with symptomatic nasolacrimal duct obstruction. One philosophy advocates "early" nasolacrimal duct probing, generally in the office - a relatively common approach in France, while others prefer to wait until the age of 12 months to offer a procedure under general anesthesia. The goal of this study is to report results of immediate office probing for congenital nasolacrimal duct obstruction (CNLDO) under age 1 year in terms of efficacy and cost. METHODS: A retrospective study was performed on 329 patients (443 eyes) treated by probing for CNLDO under the age of 12 months age. A single probing was performed at the first visit in the office under topical anesthesia without sedation. In order to determine the factors associated with failure of probing, univariate analysis was performed using the Student t-test, Pearson's, homogeneity Chi(2) or Fisher's exact tests. For cost evaluation, hypothetical estimates of spontaneous resolution month by month were used according to data in the literature, along with health insurance reimbursement data. RESULTS: The ages of the patients ranged from 2 to 11 months (mean 7.0 +/- SD 2.3). The overall success rate for cure by immediate office probing was 76.7%. Unilateral CNLDO had an 80.4% success rate whereas bilateral CNLDO had a 73.2% success rate for each eye (P=0.09). Discharge during probing was associated with failed probing (P=0.02). The cost for the spontaneous resolution strategy was 1.56 times higher than for the immediate probing strategy. A strategy which would apply the spontaneous resolution strategy for children <= 5 months and the probing strategy to children>5 months would be the most cost-effective. CONCLUSIONS: Immediate office probing between the ages of 5 to 12 months is a safe, effective method to relieve CNLDO and is the most cost effective. PMID- 26826747 TI - [Unilateral intravitreal cysts - Two rare cases]. PMID- 26826749 TI - Efficacy Comparison of 16 Interventions for Myopia Control in Children: A Network Meta-analysis. AB - PURPOSE: To determine the effectiveness of different interventions to slow down the progression of myopia in children. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov from inception to August 2014. We selected randomized controlled trials (RCTs) involving interventions for controlling the progression of myopia in children with a treatment duration of at least 1 year for analysis. MAIN OUTCOME MEASURES: The primary outcomes were mean annual change in refraction (diopters/year) and mean annual change in axial length (millimeters/year). RESULTS: Thirty RCTs (involving 5422 eyes) were identified. Network meta-analysis showed that in comparison with placebo or single vision spectacle lenses, high-dose atropine (refraction change: 0.68 [0.52-0.84]; axial length change: -0.21 [-0.28 to 0.16]), moderate-dose atropine (refraction change: 0.53 [0.28-0.77]; axial length change: -0.21 [-0.32 to -0.12]), and low-dose atropine (refraction change: 0.53 [0.21-0.85]; axial length change: -0.15 [-0.25 to -0.05]) markedly slowed myopia progression. Pirenzepine (refraction change: 0.29 [0.05-0.52]; axial length change: -0.09 [-0.17 to -0.01]), orthokeratology (axial length change: -0.15 [ 0.22 to -0.08]), and peripheral defocus modifying contact lenses (axial length change: -0.11 [-0.20 to -0.03]) showed moderate effects. Progressive addition spectacle lenses (refraction change: 0.14 [0.02-0.26]; axial length change: -0.04 [-0.09 to -0.01]) showed slight effects. CONCLUSIONS: This network analysis indicates that a range of interventions can significantly reduce myopia progression when compared with single vision spectacle lenses or placebo. In terms of refraction, atropine, pirenzepine, and progressive addition spectacle lenses were effective. In terms of axial length, atropine, orthokeratology, peripheral defocus modifying contact lenses, pirenzepine, and progressive addition spectacle lenses were effective. The most effective interventions were pharmacologic, that is, muscarinic antagonists such as atropine and pirenzepine. Certain specially designed contact lenses, including orthokeratology and peripheral defocus modifying contact lenses, had moderate effects, whereas specially designed spectacle lenses showed minimal effect. PMID- 26826748 TI - Uncorrected Hyperopia and Preschool Early Literacy: Results of the Vision in Preschoolers-Hyperopia in Preschoolers (VIP-HIP) Study. AB - PURPOSE: To compare early literacy of 4- and 5-year-old uncorrected hyperopic children with that of emmetropic children. DESIGN: Cross-sectional. PARTICIPANTS: Children attending preschool or kindergarten who had not previously worn refractive correction. METHODS: Cycloplegic refraction was used to identify hyperopia (>=3.0 to <=6.0 diopters [D] in most hyperopic meridian of at least 1 eye, astigmatism <=1.5 D, anisometropia <=1.0 D) or emmetropia (hyperopia <=1.0 D; astigmatism, anisometropia, and myopia <1.0 D). Threshold visual acuity (VA) and cover testing ruled out amblyopia or strabismus. Accommodative response, binocular near VA, and near stereoacuity were measured. MAIN OUTCOME MEASURES: Trained examiners administered the Test of Preschool Early Literacy (TOPEL), composed of Print Knowledge, Definitional Vocabulary, and Phonological Awareness subtests. RESULTS: A total of 492 children (244 hyperopes and 248 emmetropes) participated (mean age, 58 months; mean +/- standard deviation of the most hyperopic meridian, +3.78+/-0.81 D in hyperopes and +0.51+/-0.48 D in emmetropes). After adjustment for age, race/ethnicity, and parent/caregiver's education, the mean difference between hyperopes and emmetropes was -4.3 (P = 0.01) for TOPEL overall, -2.4 (P = 0.007) for Print Knowledge, -1.6 (P = 0.07) for Definitional Vocabulary, and -0.3 (P = 0.39) for Phonological Awareness. Greater deficits in TOPEL scores were observed in hyperopic children with >=4.0 D than in emmetropes (-6.8, P = 0.01 for total score; -4.0, P = 0.003 for Print Knowledge). The largest deficits in TOPEL scores were observed in hyperopic children with binocular near VA of 20/40 or worse (-8.5, P = 0.002 for total score; -4.5, P = 0.001 for Print Knowledge; -3.1, P = 0.04 for Definitional Vocabulary) or near stereoacuity of 240 seconds of arc or worse (-8.6, P < 0.001 for total score; -5.3, P < 0.001 for Print Knowledge) compared with emmetropic children. CONCLUSIONS: Uncorrected hyperopia >=4.0 D or hyperopia >=3.0 to <=6.0 D associated with reduced binocular near VA (20/40 or worse) or reduced near stereoacuity (240 seconds of arc or worse) in 4- and 5-year-old children enrolled in preschool or kindergarten is associated with significantly worse performance on a test of early literacy. PMID- 26826750 TI - [Impact of seasons, years El Nino/La Nina and rainfalls on stroke-related morbidity and mortality in Kinshasa]. AB - INTRODUCTION: The significant impact of seasonality and climate change on stroke related morbidity and mortality is well established, however, some findings on this issue are conflicting. The objective was to determine the impact of gender, age, season, year of admission, temperature, rainfall and El Nino phenomenon on ischemic and hemorrhagic strokes and fatal cases of stroke. METHODS: The study was carried out at the teaching hospital of Kinshasa, DRC, between January 1998 and December 2004. Rainy and dry seasons, elevated temperatures, indices of rainfalls El Nino years 1998, 2002 and 2004, but La Nina years 1999-2000 and neutral/normal years 2001 and 2003 were defined. RESULTS: Among 470 incident strokes, 34.5% of victims (n=162) died. Traditional seasons (small dry season, small rainy season, great dry season, great rainy season) and temperatures did not significantly (P>0.005) impact on stroke incidence. However, there was a positive association between the decrease in rainfall, El Nino, and incident ischemic strokes, but a significant positive association between the increase in rainfall, La Nina, and incident hemorrhagic strokes. Using logistic regression analysis, age >= 60 years (OR: 1.7, 95% CI: 1.2-2.5; P=0.018) and El Nino years (OR: 2, 95% CI: 1.2-3.3; P=0.009) were identified as the independent predictors of fatal strokes. CONCLUSION: Early warning systems should be developed to predict the impact of seasons and climate variability on stroke morbidity and mortality. PMID- 26826751 TI - The Online Personal Action Plan: A Tool to Transform Patient-Enabled Preventive and Chronic Care. AB - INTRODUCTION: Patient-facing online tools for managing preventive and chronic care can be a resource-effective way to increase patient agency in health promotion. Recently, Kaiser Permanente Southern California added the Online Personal Action Plan (oPAP) to the member web portal to better enable members to access information about prevention, health promotion, and care gaps. This study described Kaiser Permanente Southern California members who use oPAP, as well as how members use oPAP to close five different care gaps: hemoglobin A1c testing, pneumonia vaccination, and three cancer screenings. METHODS: Care gap closure rates between oPAP users and members not registered on the online patient portal between December 2014 and March 2015 were compared. Data were analyzed in 2015. A total of 838,638 cases (48.9% women; mean age, 49.5 years; 40.4% oPAP users) were examined. RESULTS: Adjusting for demographics, BMI, smoking status, health and insurance status, and number of open care gaps, oPAP access was associated with a somewhat greater likelihood of care gap closure within 90 days for select care gap types, particularly hemoglobin A1c testing and breast, cervical, and colorectal cancer screening among eligible members. The effect of oPAP access on care gap closure differed by certain ethnic minority groups. CONCLUSIONS: Although healthcare organizations have developed approaches to managing and closing preventive care gaps, these efforts are resource intensive. Users of oPAP are more likely than non-registered members to close gaps, especially cancer screening tests. The oPAP appears to be an effective tool at improving patient engagement in preventive health care. PMID- 26826752 TI - Balancing hope and despair at the end of life: The contribution of organ and tissue donation. AB - PURPOSE: Concern for the grieving family can moderate the intentions of critical care staff to advocate deceased organ and tissue donation. Conversely, benevolent actions may provoke distress through missed opportunities to save or transform lives. This article provides insight into the perceived benefits of organ and tissue donation for grieving families who experienced end-of-life care in the intensive care unit. METHODS: Data were collected via semistructured, face-to face or telephone interviews with 43 participants from 31 donor families. Audio recordings were transcribed verbatim and subjected to qualitative content analysis. RESULTS: The study findings affirmed the importance of person-centered end-of-life care. Donor families shared examples of good-quality care and communication that contained the hallmarks of compassion, respect, dignity, and choice. We uncovered a trajectory of hope and despair in which the option of organ and tissue donation appeared to give meaning to the life and death of the deceased person and was comforting to some families in their bereavement. CONCLUSIONS: Our study findings underlined the significance of donation decision making for grieving families. Organ and tissue donation has the potential to balance hope and despair at the end of life when the wishes of the dying, deceased, and bereaved are fulfilled. PMID- 26826753 TI - Oxidative stress-mediated N-terminal protein modifications and MS-based approaches for N-terminal proteomics. AB - The N-termini of peptides and proteins can be subjected to highly diverse modifications, including acetylation, myristoylation, pyroglutamylation, and epimerization. These modifications affect protein stability, localization, and activity as well as alter the chemical properties of the N-terminus. Oxidative stress is known to induce the direct oxidation of amino acid side chains and peptide backbones in proteins. Alternatively, polyunsaturated fatty acids can be oxidized to lipid hydroperoxides, which further decompose to form highly reactive aldehydes such as 4-oxo-2(E)-nonenal (ONE) and 4-hydroxy-2(E)-nonenal (HNE). ONE and HNE modify various amino acid residues and induce protein cross-linking. However, there have been few studies on oxidative stress-mediated N-terminal modifications and the resulting functional changes. Our recent studies have reported several novel N-terminal modifications that result in the formation of alpha-ketoamide, transamination, cyclization, and epimerization. These novel N terminal modifications are the focus of this review. We also outline recent advances in approaches for N-terminal analysis, which have been developed over the last several decades. PMID- 26826754 TI - Third hand smoke--A hidden demon. PMID- 26826755 TI - Screen-printed digital microfluidics combined with surface acoustic wave nebulization for hydrogen-deuterium exchange measurements. AB - An inexpensive digital microfluidic (DMF) chip was fabricated by screen-printing electrodes on a sheet of polyimide. This device was manually integrated with surface acoustic wave nebulization (SAWN) MS to conduct hydrogen/deuterium exchange (HDX) of peptides. The HDX experiment was performed by DMF mixing of one aqueous droplet of angiotensin II with a second containing various concentrations of D2O. Subsequently, the degree of HDX was measured immediately by SAWN-MS. As expected for a small peptide, the isotopically resolved mass spectrum for angiotensin revealed that maximum deuterium exchange was achieved using 50% D2O. Additionally, using SAWN-MS alone, the global HDX kinetics of ubiquitin were found to be similar to published NMR data and back exchange rates for the uncooled apparatus using high inlet capillary temperatures was less than 6%. PMID- 26826756 TI - Status and perspectives of claims data analyses in Germany-A systematic review. AB - BACKGROUND: The aim of this article is to evaluate the status, development, and perspectives of German claims data analyses in the international and health political context. METHODS: We conducted a comprehensive literature search in PubMed, Scopus, and DIMDI to identify empirical and methodological articles focusing on health insurance claims data studies published between 2000 and 2014. Inclusion criteria were (1) English/German full text articles or chapters in edited books that (2) focused on the claims data of statutory health insurance funds. FINDINGS: In total, 435 articles were included. Over time, the number of claims data studies has increased strongly and the frequency of policy-relevant research types increased. Along with the historical improvement path of claims data in Germany, we observed a rising percentage of international publications and an increase in the average quality of publications. In contrast to the US or Canada where comprehensive databases have been established, the most common data source in this search was data from a single SHI fund, while databases were rarely used. CONCLUSIONS: Claims data are an important source of information for healthcare stakeholders, and their use for research purposes has further increased during recent years in Germany. Despite its potential in optimising the health system, we found a lack of German comprehensive all-payer claims databases compared to the US and Canada. PMID- 26826757 TI - Development of a Performance Improvement Program: A Workplace-Based Educational Intervention on Magnetic Resonance Imaging in Spinal Trauma. AB - OBJECTIVE: Performance improvement (PI) programs are an educational tool used to analyze clinical performance of clinicians. The effect of this tool has not been fully explored in orthopedic and trauma surgery. DESIGN AND SETTING: A needs assessment was conducted in connection with a worldwide webinar on magnetic resonance imaging in spinal injuries to identify the clinical need for an educational intervention. A 3-step PI process was defined and implemented over a 6-month period in 1 hospital department. Opportunities for improvement were identified by applying a 10-item quality checklist to 26 cases. A focused educational intervention was delivered to address the identified gaps, and a set of 22 posteducation cases was compared. PARTICIPANTS: The department of radiology and the department of trauma surgery of a level I university hospital participated in this study. RESULTS: A total of 26 cases collected before the educational intervention showed several areas for potential improvement. Important information was not provided by the surgeons in their communication with the radiologist. The educational intervention outlined the data and suggested actions. Comparing the information transfer of the preintervention and postintervention data, there was a significant improvement following the intervention (p = 0.0013). CONCLUSION: Our PI program was able to demonstrate a significant influence on the behavior and the attitude of surgeons and radiologists. PMID- 26826758 TI - [Management of gastroesophageal reflux in children. Single centre experience in conventional and laparoscopic Nissen fundoplication in the last 15 years]. AB - INTRODUCTION: Nissen fundoplication (NF) is the most used and effective technique for the treatment of gastroesophageal reflux in children. The laparoscopic approach (LNF) is safe, with low morbidity and high success rate, although some cases require a conventional approach (CNF). The aim of the study is to compare the results between LNF and CNF in our centre. MATERIAL AND METHODS: A retrospective review was performed on patients <14years after NF between 2000 and 2015. A comparison was made of the complications, hospital stay, and follow-up for both approaches. RESULTS: Of the total 75 NF performed, 49 (65.3%) were LNF, 23 (30.7%) CNF, and 3 (4.0%) reconversions. Concomitant laparoscopic gastrostomy was performed in 10.7%, and open gastrostomy in 5.3% of cases. Prior to NF, 10.7% had a gastrostomy. The mean age was 4 years and 68.7% were male. Of the diagnoses, 36% had encephalopathy, 14.7% hiatal hernia, 5.4% oesophageal atresia, and 5.4% an acute life-threatening event. No differences were found in operation time. More than two-thirds (36%) had complications, which were more frequent in the CNF (OR=3.30, 95%CI: 1.1-9.6). The hospital-stay decreased by 9 days in the LNF (95%CI: 5.5-13.5). Mean follow-up was 26 months (95%CI: 20.9-31.6). Mortality during follow-up was of 5.3% (5 respiratory failure, 1 sudden cardiac death, and 2 due to complications of the encephalopathy), 4.2% required re-fundoplication, 15.8% had symptomatic improvement, and 64.0% had absence of symptoms. CONCLUSIONS: The LNF is an effective technique for the treatment of gastroesophageal reflux, with lower morbidity and shorter hospital stay than CNF. It is recommended as the first surgical option. PMID- 26826759 TI - ["Warning! Oxygen is just makeup". Author's reply]. PMID- 26826761 TI - [Appointments requested as urgent: Impact on the clinics and clinical characteristics]. PMID- 26826760 TI - [Surgical closure of patent ductus arteriosus in premature neonates: Does the surgical technique affect the outcome?] AB - INTRODUCTION: Surgical closure of patent ductus arteriosus in premature neonates is an aggressive technique and is not free of complications. A study was designed with the aim of describing our experience with a less invasive technique, the extra-pleural approach via a posterior minithoracotomy, and to compare the results with the classic transpleural approach. PATIENTS AND METHODS: A retrospective cohort study was conducted on premature neonates on whom surgical closure of the ductus was performed during a ten-year period (March 2005 to March 2015). A comparison was made of the acute complications, the outcomes on discharge, and follow-up, between the extra-pleural approach and the classic transpleural approach. The study included 48 patients, 30 in the classical approach and 18 in the extra-pleural group. RESULTS: The demographic and pre operative characteristics were similar in both groups. No differences were found between the 2 groups in the incidence of acute post-operative complications (56.6 vs. 44.4%), on the dependence on oxygen at 36 weeks (33.3 vs. 55.5%), or in hospital mortality (10 vs. 16.6%). As regards the short-term progress, the extra pleural group required fewer days until the withdrawal of supplementary oxygen (36.3 vs. 28.9) and until hospital discharge (67.5 vs. 53.2), although only the time until extubation achieved a statistically significant difference (11.5 vs. 2.7, P=.03). CONCLUSIONS: The extra-plural approach by posterior minithoracotomy for the surgical closure of ductus in the premature infant is viable and could bring some clinical benefits in the short-term. PMID- 26826762 TI - Cooking With Whole Grains: A Skills-Based Training for Child Care Providers. PMID- 26826763 TI - Streptococcus thermophilus urease activity boosts Lactobacillus delbrueckii subsp. bulgaricus homolactic fermentation. AB - The proto-cooperation between Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus in the yogurt consortium enhances the growth rate and size of each population. In contrast, the independent growth of the two species in milk leads to a slower growth rate and a smaller population size. In this study, we report the first evidence that the urease activity of S. thermophilus increases the intracellular pH of L. delbrueckii in the absence of carbon source. However, in milk, in the presence of lactose the alkalizing effect of urea-derived ammonia was not detectable. Nevertheless, based on glucose consumption and lactic acid production at different pHin, L. delbrueckii showed an optimum of glycolysis and homolactic fermentation at alkaline pH values. In milk, we observed that ammonia provided by urea hydrolysis boosted lactic acid production in S. thermophilus and in L. delbrueckii when the species were grown alone or in combination. Therefore, we propose that urease activity acts as an altruistic cooperative trait, which is costly for urease-positive individuals but provides a local benefit because other individuals can take advantage of urease dependent ammonia release. PMID- 26826764 TI - A t(11;14)(p13;q11.2) in myelofibrosis following polycythemia vera. AB - Chromosomal abnormalities at 14q11, which encodes the T-cell receptor alpha and delta chain genes, are generally specific for T-cell malignancies, and are rarely reported in other malignancies. We report a novel t(11;14)(p13;q11.2) in a patient with myelofibrosis (MF) following polycythemia vera (PV). This 55-year old male developed post-PV MF 12 years after the initial diagnosis of PV. He had a normal karyotype at polycythemic disease stage, t(11;14)(p13;q11.2) was newly detected at the time of fibrotic transformation. Therefore, it is likely that this clonal chromosomal abnormality was associated with progression of disease. PMID- 26826765 TI - Modelling and simulation of the mechanical response of a Dacron graft in the pressurization test and an end-to-end anastomosis. AB - This work presents the modeling and simulation of the mechanical response of a Dacron graft in the pressurization test and its clinical application in the analysis of an end-to-end anastomosis. Both problems are studied via an anisotropic constitutive model that was calibrated by means of previously reported uniaxial tensile tests. First, the simulation of the pressurization test allows the validation of the experimental material characterization that included tests carried out for different levels of axial stretching. Then, the analysis of an end-to-end anastomosis under an idealized geometry is proposed. This case consists in evaluating the mechanical performance of the graft together with the stresses and deformations in the neighborhood of the Dacron with the artery. This research contributes important data to understand the functioning of the graft and the possibility of extending the analysis to complex numerical cases like its insertion in the aortic arch. PMID- 26826766 TI - The effect of concomitant glenohumeral joint capsule release during rotator cuff repair--a comparative study. AB - BACKGROUND: There is debate as to whether to operate or to defer surgery on patients with concomitant rotator cuff tear and shoulder stiffness. The purpose of this study was therefore to compare the outcomes in those patients who had both their rotator cuff tear and shoulder stiffness treated with the outcomes of patients who had a rotator cuff repair but no stiffness. METHODS: Twenty-five patients formed the stiffness group (receiving a concomitant rotator cuff repair and manipulation under anesthesia +/- arthroscopic capsular release for preoperative ipsilateral stiffness), and a chronologically matched group of 170 rotator cuff repair-only patients formed the nonstiffness group. Patients ranked their pain and function scores preoperatively and at 1 week, 6 weeks, 12 weeks, 6 months, and 2 years postoperatively; examiners recorded range of motion, strength, and presence of impingement signs. Repair integrity was determined using ultrasound. RESULTS: Patients from both groups had significantly improved clinical outcomes at the 2-year follow-up compared with preoperative values. Range of motion was similar between groups at 2 years for forward flexion, abduction, and external rotation, whereas the nonstiffness group had a superior range of internal rotation (P = .014). Stiffness patients had 0 of 25 (0%) retears at 2 years compared with 34 of 170 (20%) in the nonstiffness group (P = .009). CONCLUSIONS: The good outcomes of rotator cuff repair with glenohumeral capsular release disproved our hypothesis and suggest that there is no advantage in delaying repair of a rotator cuff tear to allow stiffness to resolve and that stiffness confers an advantage in terms of repair integrity. LEVEL OF EVIDENCE: Level III; Retrospective Cohort Design; Treatment Study. PMID- 26826768 TI - Rapid Electrocardiogram Evolution in a Dialysis Patient. PMID- 26826767 TI - Physician in Triage Versus Rotational Patient Assignment. AB - BACKGROUND: Physician in triage and rotational patient assignment are different front-end processes that are designed to improve patient flow, but there are little or no data comparing them. OBJECTIVE: To compare physician in triage with rotational patient assignment with respect to multiple emergency department (ED) operational metrics. METHODS: Design-Retrospective cohort review. Patients Patients seen on 23 days on which we utilized a physician in triage with those patients seen on 23 matched days when we utilized rotational patient assignment. RESULTS: There were 1,869 visits during physician in triage and 1,906 visits during rotational patient assignment. In a simple comparison, rotational patient assignment was associated with a lower median length of stay (LOS) than physician in triage (219 min vs. 233 min; difference of 14 min; 95% confidence interval [CI] 5-27 min). In a multivariate linear regression incorporating multiple confounders, there was a nonsignificant reduction in the geometric mean LOS in rotational patient assignment vs. physician in triage (204 min vs. 217 min; reduction of 6.25%; 95% CI -3.6% to 15.2%). There were no significant differences between groups for left before being seen, left subsequent to being seen, early (within 72 h) returns, early returns with admission, or complaint ratio. CONCLUSIONS: In a single-site study, there were no statistically significant differences in important ED operational metrics between a physician in triage model and a rotational patient assignment model after adjusting for confounders. PMID- 26826769 TI - Efficacy of Different Medical Therapies for the Treatment of Acute Laryngeal Attacks of Hereditary Angioedema due to C1-esterase Inhibitor Deficiency. AB - BACKGROUND: Hereditary angioedema (HAE) is a rare disease characterized by C1 esterase inhibitor (C1-INH) deficiency, resulting in periodic attacks of acute edema, which can be life-threatening if they occur in the upper airway. No head to-head comparisons of different treatment options for acute HAE attacks are available. Because immediate symptom relief is critical for potentially life threatening laryngeal attacks, it is important to determine the treatment option that provides optimal treatment response. OBJECTIVE: Review and compare data from clinical studies that evaluated the efficacy and safety of treatments for laryngeal HAE attacks. METHODS: We conducted an indirect comparison of clinical outcomes from prospective studies for treatment of 881 acute laryngeal attacks with plasma-derived C1-INH concentrate (pdC1-INH) at fixed doses (500 or 1000 U) or a body weight-adjusted dose (20 U/kg), recombinant C1-INH concentrate at a fixed dose (2100 U), or a body weight-adjusted dose (50 U/kg), icatibant (30 mg), or ecallantide (30 mg). Comparisons included time to onset of symptom relief and need for re-dosing or emergency procedures. RESULTS: The median time to onset of symptom relief ranged between 15 min and approximately 2 h, and was shortest with body weight-adjusted doses of pdC1-INH. The proportion of laryngeal attacks with re-dosing ranged between 0% and 72%. No re-dosing was needed after treatment with a single body weight-adjusted dose of pdC1-INH (48 attacks). CONCLUSIONS: Available data suggest that among different HAE treatments, body weight-adjusted pdC1-INH (20 U/kg) provides the most reliable treatment response for treatment of laryngeal HAE attacks. PMID- 26826770 TI - [Evolution of the therapeutic management of varicoceles: Analysis of French national coding database (2006-2014)]. AB - OBJECTIVE: The varicocele is a venous abnormality frequently found in humans (1/10). Although the recommendations for management of this pathology are clear, two therapeutic options can be discussed: surgery or radiological embolisation. We wanted to study the evolution of the therapeutic management of varicocele using the French national coding database. METHODS: Analysis of database from the "Agence technique de l'information sur l'hospitalisation" (ATIH) (number of surgical procedures and interventional radiology used in the treatment of varicocele for the period 2006-2014). The common classification of medical procedures (CCAM) was used to extract the codes for surgery and radiological embolisation. Then we recorded the corresponding "Groupes homogenes de malades" (GHM), excluding those with a different primary diagnosis of varicocele cure. RESULTS: The number of surgical procedures and radiological embolisation performed for the treatment of varicocele increased from 3626 to 4007 procedures (+10.5%) between 2006 and 2014. While the frequency of interventional radiology (embolization pampiniform plexus) increased by 73.9%, surgery procedures (by direct approach or laparoscopy) decreased by 31.4% throughout the study (2006 2014). Thus in 2006, 60.2% of therapeutic procedures were performed surgically and 39.8% by radiological embolisation. In 2014, 37.4% of therapeutic procedures were performed surgically and 62.6% by embolization. CONCLUSION: The analysis of French national database has confirmed a change in the therapeutic management of varicocele between 2006 and 2014. The minimally invasive treatment by radiological embolisation is currently favored in France and surgery pushed into the background. In 2014, more than one therapeutic management out of two was performed in interventional radiology. LEVEL OF EVIDENCE: 4. PMID- 26826771 TI - [Anticholinergics do not affect the sexual function in women diagnosed with multiple sclerosis]. AB - AIM: Determine if the initiation of an anticholinergic treatment affects the sexual function in women diagnosed with multiple sclerosis (MS). METHODS: It was a single-centre prospective open label study on 18 women affected by MS, with a clinical overactive bladder syndrome, and examined before and after anticholinergic treatment. Several variables were studied before and after treatment: the total anticholinergic load (Anticholinergic Drug Scale [ADS]), the Female Sexual Function Index, the Urinary Symptom Profile (USP) and functional status (EDSS, MIF). Quantitative variables were analyzed using Student's test. RESULTS: Eighteen women with an average age of 48.3 years old (+/-10.7 years), average EDSS of 4.6 (+/-1.5) were examined before and after anticholinergic treatment (solifenacin and trospium). Anticholinergic load at baseline was 0.33 (+/-0.5) and 3.44 (+/-0.70) after treatment (P<0.0001). The initiation of an anticholinergic treatment allowed a significant improvement on the subscore OAB USP (10.25+/-4.3 to 6.22+/-3 P=0.01). No significant impacts of the anticholinergic load on the Female Sexual Function Index (FSFI) score (18.9+/ 10.8 to 21.2+/-10.8 P=0.06) and sub-items lubrification (3.6+/-2.2 to 3.7+/-2.2 P=0.6), pain (3.6+/-2.5 to 4.2+/-2.3 P=0.4), desire (3+/-1.2 to 3+/-1.5 P=0.7), orgasm (2.7+/-2.1 to 3+/-2.4 P=0.4), satisfaction (3.9+/- to 4+/-2 p=0.9), arousal (2.9+/-2 to 3.3+/-1.8 P=0.8) was evidenced. CONCLUSION: In this limited series of "naive" patients with MS, no impact of anticholinergic therapy on vaginal lubrication or sexual quality was observed. LEVEL OF EVIDENCE: 4. PMID- 26826773 TI - Prediabetes and coronary artery disease: Outcome after revascularization procedures. AB - OBJECTIVE: To assess the long-term association between prediabetes and an increased risk of cardiovascular events in patients with coronary artery disease and percutaneous coronary intervention (PCI). METHODS: A retrospective cohort study. We searched our database to identify all PCI procedures performed in 2010. Patients with no diabetes and HbA1c measurement in the index hospitalization were enrolled and divided into two groups based on HbA1c value: 5.7-6.5% for prediabetes and <5.7% for controls. Demographic, clinical, and procedure-related variables were recorded. Study endpoints were mortality, hospital admissions, myocardial infarction (MI), and revascularization procedures. RESULTS: The study population consisted of 132 subjects (82.6% males, age: 65.26 +/- 12.46 years). No difference was found as regards distribution of demographic, clinical, and procedure-related variables. A majority (64.1%) of PCI procedures were performed for ST-segment elevation MI. Prevalence of prediabetes was 40.2%. After a mean follow-up period of 42.3 +/- 3.6 months, no differences were found in outcomes between the prediabetes and control groups in total mortality (5.4% vs 1.9%; relative risk [RR] 2.86, 95% confidence interval [95% CI] 0.27-30.44; P=.56), non cardiovascular mortality (2.7% vs 1.9%; RR 1.43, 95% CI 0.93-22.18; P=.79), hospital admissions (19% vs 25%; RR 1.13, 95%CI 0.73-1.73; P=.57), MI (3% vs 1%; RR 4.28, 95%CI .46-39.52; P=.30), or target lesion revascularization (3% vs 6%); RR .70, 95%CI .18-2.61; P=.72). CONCLUSIONS: Prediabetes, as determined by HbA1c (5.7%-6.5%), is not associated with long-term adverse cardiovascular outcomes in patients with CAD and PCI. PMID- 26826772 TI - Effective adverse event reduction with bolus-basal versus sliding scale insulin therapy in patients with diabetes during conventional hospitalization: Systematic review and meta-analysis. AB - INTRODUCTION: The aim of this review was to assess the effectiveness to reduce clinical adverse events and safety of insulin administered in basal-bolus corrector or basal-corrector regimens (BB) versus a sliding scale scheme (SS) in patients with diabetes or newly diagnosed hyperglycemia admitted to a conventional (not critical) medical or surgical hospital ward. METHOD: A Medline search was conducted. The Odds ratio was the main summary measure. A random effects model with the Mantel-Haenszel procedure was used. RESULTS: A total of 957 citations were collected, of which nine were finally included in the systematic review. Patients in the BB group had better blood glucose control than those with SS. Overall, there was a nonsignificant trend to a lower risk of adverse events in the BB as compared to the SS group (OR 0.67 [95% CI 0.22 to 2.04], [I(2)=71%]). There was a nonsignificant trend to an increased risk of hypoglycemia in the BB group (OR 2.29 [95% CI 0.50 to 10.49] [I(2)=70%]). CONCLUSION: Despite its benefit for glycemic control during hospitalization, this review did not show that use of the BB scheme decreases clinical events in patients hospitalized in a conventional ward. Because of heterogeneity of the results, we think that clinical trials are needed addressing its effect in patient subgroups in which the BB scheme may be used safely and with longer follow-up periods. PMID- 26826774 TI - Diabetes mellitus and Alzheimer's disease: An unforgettable relation. PMID- 26826775 TI - Effects of exposure to pyrethroid cyfluthrin on serotonin and dopamine levels in brain regions of male rats. AB - The effects of cyfluthrin oral exposure (1, 5, 10 and 20mg/kg bw, 6 days) on brain region monoamine levels of male rats were examined. Cyfluthrin-treated rats (1, 5 and 10mg/kg bw, orally 6 days), had no visible injury, i.e., no clinical signs of dysfunction were observed. However, rats treated with cyfluthrin at the highest dose (20mg/kg bw, orally 6 days) showed skeletal muscle contraction in the hind limbs, slight movement incoordination without any signs of dyskinesia and tremor after 1-2h of treatment. These signs were reversible at 6h after dose. After last dose of cyfluthrin, dopamine (DA) and serotonin (5-HT) and its metabolites levels were determined in brain regions hypothalamus, midbrain, hippocampus, striatum and prefrontal cortex by HPLC. Cyfluthrin (1mg/kg bw, orally 6 days) did not affect the DA, 5-HT and metabolites levels in the brain regions studied. Cyfluthrin (5, 10 and 20mg/kg bw, orally 6 days) caused a statistically significant decrease in DA and its metabolites DOPAC and HVA levels and in 5-HT and its metabolite 5-HIAA levels in a brain region- and dose-related manner. Moreover, cyfluthrin (20mg/kg bw, orally 6 days) evoked a statistically significant increase in 5-HT turnover in striatum and midbrain, and in DA turnover in striatum and prefrontal cortex. These findings indicate that serotoninergic and dopaminergic neurotransmission is affected by exposure to cyfluthrin and may contribute to the overall spectrum of neurotoxicity caused by this pyrethroid. PMID- 26826776 TI - Self-reported smoking, serum cotinine, and blood DNA methylation. AB - BACKGROUND: Epigenome-wide profiling of DNA methylation pattern with respect to tobacco smoking has given rise to a new measure of smoking exposure. We investigated the relationships of methylation markers with both cotinine, an established marker of internal smoking exposure, and self-reported smoking. METHODS: Blood DNA methylation levels across the genome and serum cotinine were measured in 1000 older adults aged 50-75 years. Epigenome-wide scans were performed to identify methylation markers associated with cotinine. The inter dose-response relationships between the number of cigarettes smoked per day, cotinine concentration, and DNA methylation were modeled by restricted cubic spline regression. RESULTS: Of 61 CpGs that passed the genome-wide significance threshold (p<1.13*10(-7)), 40 CpGs in 25 chromosomal regions were successfully replicated, showing 0.2-3% demethylation per 10ng/ml increases in cotinine. The strongest associations were observed for several loci at AHRR, F2RL3, 2q37.1, 6p21.33, and GFI1 that were previously identified to be related to self-reported smoking. One locus at RAB34 was newly discovered. Both cotinine and methylation markers exhibited non-linear relationships with the number of cigarettes smoked per day, where the highest rates of increase in cotinine and decreases in methylation were observed at low smoking intensity (1-15 cigarettes/day) and plateaued at high smoking intensity (>15-20 cigarettes/day). A clear linear relationship was observed between cotinine concentration and methylation level. Both cotinine and methylation markers showed similar accuracy in distinguishing current from never smoker, but only methylation markers distinguished former from never smoker with high accuracy. CONCLUSIONS: Our study corroborates and expands the list of smoking-associated DNA methylation markers. Methylation levels were linearly related to cotinine concentration and provided accurate measures for both current and past smoking exposure. PMID- 26826778 TI - [Intestinal infiltration of high-grade large T-cell non-Hodgkin lymphoma with cyclin-D1 overexpression and aberrant CD79a expression in a patient with a diagnosis of tumour stage mycosis fungoides]. PMID- 26826779 TI - Listeria monocytogenes cholecystitis in an immunocompetent patient. PMID- 26826777 TI - [Impact of the incorporation of a nurse in an inflammatory bowel disease unit]. AB - INTRODUCTION: Multidisciplinary units are needed because of the growing complexity and volume of patients with inflammatory bowel disease (IBD). OBJECTIVES: To evaluate the healthcare, economic and research impact of incorporating a nurse into the IBD unit of the Puerta de Hierro Majadahonda University Hospital. METHODS: We prospectively recorded the activity carried out by the nurse of the IBD unit from March 2010 to December 2014. RESULTS: During this period, healthcare demand progressively increased, with 1,558 patients being attended by our unit. The healthcare provided by the nurse included 5,293 electronic mails and 678 telephone calls. We estimated that this activity represented a saving of 3,504 in-person medical consultations and 852 accident and emergency department visits. Other activities consisted of monitoring treatments with biological and non-biological agents (8,371 laboratory tests), extraction of 342 blood samples, follow-up of 1047 diagnostic tests and consultations with other medical specialties, health education in self administration of drugs in 114 patients, the performance of 158 granulocyte apheresis procedures, and participation in 25 research projects. CONCLUSION: The incorporation of a specialised nurse in an IBD unit had major economic, healthcare and research benefits. PMID- 26826780 TI - The influence of electrodialytic remediation on dioxin (PCDD/PCDF) levels in fly ash and air pollution control residues. AB - Fly ash and Air Pollution Control (APC) residues collected from three municipal solid waste incinerators in Denmark and Greenland were treated by electrodialytic remediation at pilot scale for 8-10 h. This work presents for the first time the effect of electrodialytic treatment on polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF), and how these levels impact on the valorization options for fly ash and APC residue. PCDD/PCDF levels in the original residues ranged between 4.85 and 197 ng g(-1), being higher for the electrostatic precipitator fly ash. The toxic equivalent (TEQ) varied ten fold, ranging 0.18-2.0 ng g(-1) I-TEQ, with penta and hexa-homologs being most significant for toxicity. After the electrodialytic treatment PCDD/PCDF levels increased in the residues (between 1.4 and 2.0 times). This does not mean PCDD/PCDF were synthesized, but else that soluble materials dissolve, leaving behind the non-water soluble compounds, such as PCDD/PCDF. According to the Basel Convention, PCDD/PCDF levels in these materials is low (<15 MUg WHO-TEQ kg(-1)) and the fly ash and APC residue could eventually be valorized, for instance as construction material, provided end-of-waste criteria are set and that a risk assessment of individual options is carried out, including the end-of-life stage when the materials become waste again. PMID- 26826781 TI - Enhanced degradation of phenol by Sphingomonas sp. GY2B with resistance towards suboptimal environment through adsorption on kaolinite. AB - The effects of clay minerals on microbial degradation of phenol under unfavorable environmental conditions were investigated. Degradation of phenol by Sphingomonas sp. GY2B adsorbed on kaolinite, montmorillonite, and vermiculite were evaluated in comparison with free bacteria under optimal conditions. Kaolinite was found to be the most effective in accelerating degradation rate (reducing the degradation time) as well as improving degradation efficiency (increasing the percentage of phenol degraded), with GY2B/kaolinite complex achieving a degradation efficiency of 96% within 6 h. GY2B adsorbed on kaolinite was more competent than free GY2B in degradation under conditions with high phenol concentrations and at alkaline pH. Kaolinite reduced the time required for degradation by 8-12 h and improved the degradation efficiency by as much as 82% at high phenol concentrations. Meanwhile, the GY2B/kaolinite complex reduced the degradation time by 24 h and improved the degradation efficiency by 46% at pH 12. The improvement was partially due to the buffering effects of kaolinite. It was also shown that Cr(VI) and kaolinite synergistically enhanced the degradation by GY2B, with Cr(VI) and kaolinite both increasing the degradation rate and kaolinite being primarily responsible for enhanced degradation efficiency. These results showed one of the common clay minerals, kaolinite, is able to significantly improve the microbial degradation performance, and protect microorganisms against unfavorable environment. Kaolinite can collaborate with Cr(VI) to further improve the microbial degradation performance. It is implied that clay minerals have great potential to be applied in enhancing the biodegradation of phenol. PMID- 26826782 TI - Individual design of the anterolateral thigh flap for functional reconstruction after hemiglossectomy: experience with 238 patients. AB - The aim of this study was to evaluate tongue function in patients with oral cancer treated surgically and reconstructed with anterolateral thigh free flaps (ALTFs). Patients (N=238) underwent primary reconstruction after hemiglossectomy between September 2012 and October 2014. Patients were divided into two groups according to the flap design: 'individual design' (ABC flap) and 'common design'. Patients were followed postoperatively and assessed after 6 months for the following functional outcomes: speech, deglutition, tongue mobility, and donor site morbidity. Intelligibility and deglutition were each scored by an independent investigator. Data were analyzed using SPSS version 16.0 software. No differences in mean speech intelligibility scores were observed between the two groups (good: P=0.908; acceptable: P=0.881). However, the ABC flap offered recovery advantages for swallowing capacity compared to the common design flap (MTF classification good: P=0.028; acceptable: P=0.001). The individualized ABC flap not only provides volume but also preserves mobility, speech intelligibility, and swallowing capacity. ALTFs require further improvement for the individualized functional reconstruction of the tongue after hemiglossectomy, but this work lays the foundation for these improvements. PMID- 26826783 TI - Beyond Tsetse--Implications for Research and Control of Human African Trypanosomiasis Epidemics. AB - Epidemics of both forms of human African trypanosomiasis (HAT) are confined to spatially stable foci in Sub-Saharan Africa while tsetse distribution is widespread. Infection rates of Trypanosoma brucei gambiense in tsetse are extremely low and cannot account for the catastrophic epidemics of Gambian HAT (gHAT) seen over the past century. Here we examine the origins of gHAT epidemics and evidence implicating human genetics in HAT epidemiology. We discuss the role of stress causing breakdown of heritable tolerance in silent disease carriers generating gHAT outbreaks and see how peculiarities in the epidemiologies of gHAT and Rhodesian HAT (rHAT) impact on strategies for disease control. PMID- 26826784 TI - Insecticide Resistance in African Anopheles Mosquitoes: A Worsening Situation that Needs Urgent Action to Maintain Malaria Control. AB - Malaria control is reliant on insecticides to control the mosquito vector. As efforts to control the disease have intensified, so has the selection pressure on mosquitoes to develop resistance to these insecticides. The distribution and strength of this resistance has increased dramatically in recent years and now threatens the success of control programs. This review provides an update on the current status of resistance to the major insecticide classes in African malaria vectors, considers the evidence that this resistance is already compromising malaria control efforts, and looks to the future to highlight some of the new insecticide-based tools under development and the challenges in ensuring they are most effectively deployed to manage resistance. PMID- 26826785 TI - Control Issues. PMID- 26826786 TI - The age of multiplexity: recruitment and interactions of Polycomb complexes in plants. AB - Polycomb group (PcG) proteins form distinct complexes that modify chromatin by histone H3 methylation and H2A mono-ubiquitination leading to chromatin compaction and epigenetic repression of target genes. A network of PcG protein complexes, associated partners and antagonistically acting chromatin modifiers is essential to regulate developmental transitions and cell fate in all multicellular eukaryotes. In this review, we discuss insights on the subfunctionalization of PcG complexes and their modes of recruitment to target sites based on data from the model organism Arabidopsis thaliana. PMID- 26826787 TI - TAVR--A new way to treat ventricular storm and ventricular fibrillation. PMID- 26826788 TI - Bioresorbable Scaffold vs. Second Generation Drug Eluting Stent in Long Coronary Lesions requiring Overlap: A Propensity-Matched Comparison (the UNDERDOGS study). AB - BACKGROUND: Randomized clinical trials on bioresorbable scaffolds (BRS) enrolled patients with simple coronary lesions. The present study was sought to give preliminary findings about safety of BRS implantation in overlap in long coronary lesions. METHODS: From June 2012 to January 2015, we prospectively collected data from 162 consecutive patients receiving overlapping BRS implantation in the 16 participating institutions. We applied a propensity-score to match BRS-treated patients with 162 patients receiving second generation drug eluting stents (DES) in overlap. The primary endpoint was a device-oriented endpoint (DOCE), including cardiac death, target vessel myocardial infarction, and target lesion revascularization. RESULTS: DOCE rate did not significantly differ between the two groups (5.6% in BRS group vs. 7.4% in DES group, HR 0.79, 95%CI 0.37-3.55, p=0.6). Also stent/scaffold thrombosis did not differ between groups (1.2% in BRS group vs. 1.9% in DES group, p=0.6). Occurrence of procedural-related myocardial injury was significantly higher in the BRS group (25% vs. 12%, p=0.001), although it was not related to DOCE (HR 1.1, 95%CI 0.97-1.2, p=0.2). Imaging techniques and enhanced stent visualization systems were significantly more employed in the BRS group (p=0.0001 for both). Procedure length, fluoroscopy time and contrast dye amount were significantly higher in the BRS group (p=0.001, p=0.001 and p=0.01, respectively). CONCLUSIONS: Overlapping BRS utilization in long coronary lesions showed a comparable DOCE rate at 1year if compared to second generation DES. Further and larger studies are on demand to confirm our findings. PMID- 26826789 TI - Cardiovascular risk markers in patients with primary aldosteronism: A systematic review and meta-analysis of literature studies. AB - BACKGROUND/OBJECTIVES: Several studies reported an increased cardiovascular (CV) morbidity and mortality in patients with primary aldosteronism (PA). We performed a meta-analysis on the impact of PA on major markers of CV risk. METHODS: Studies on the relationship between PA and common carotid artery intima-media thickness (CCA-IMT), prevalence of carotid plaques, flow-mediated dilation (FMD), nitrate mediated dilation (NMD), pulse-wave velocity (PWV), augmentation index (AIx), and ankle-brachial index (ABI) were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. RESULTS: 12 case-control studies (445 cases, 472 controls) were included. Compared to subjects with essential hypertension (EH), PA patients showed a higher CCA-IMT (MD: 0.12 mm; 95% CI: 0.09, 0.16; P<0.00001), and a higher aortic-PWV (272 cases and 240 controls, MD: 1.39 m/s; 95% CI: 0.90, 1.87; P<0.00001). In contrast, non-significant differences were found in AIx and AIx normalized to a heart rate of 75 beats per minute (AIx@75). When compared to normotensive subjects, PA patients showed significantly higher CCA-IMT (MD: 0.16 mm; 95% CI: 0.05, 0.27; P=0.004), aortic PWV (MD: 3.74 m/s; 95% CI: 3.43, 4.05; P<0.00001), AIx@75 (MD: 8.59%; 95% CI: 0.69, 16.50; P=0.03), and a significantly lower FMD (MD: -2.52%; 95% CI: -3.64, 1.40; P<0.0001). Sensitivity and subgroup analyses substantially confirmed our results. Metaregression models showed that male gender, diabetes, and smoking habit impact on the observed results. CONCLUSIONS: PA appears significantly associated with markers of subclinical atherosclerosis and CV risk. These findings could help establish more specific CV prevention strategies in this clinical setting. PMID- 26826791 TI - Dynamic application of microprojection arrays to skin induces circulating protein extravasation for enhanced biomarker capture and detection. AB - Surface modified microprojection arrays are a needle-free alternative to capture circulating biomarkers from the skin in vivo for diagnosis. The concentration and turnover of biomarkers in the interstitial fluid, however, may limit the amount of biomarker that can be accessed by microprojection arrays and ultimately their capture efficiency. Here we report that microprojection array insertion induces protein extravasation from blood vessels and increases the concentration of biomarkers in skin, which can synergistically improve biomarker capture. Regions of blood vessels in skin were identified in the upper dermis and subcutaneous tissue by multi-photon microscopy. Insertion of microprojection array designs with varying projection length (40-190 MUm), density (5000-20,408 proj.cm(-2)) and array size (4-36 mm(2)) did not affect the degree of extravasation. Furthermore, the location of extravasated protein did not correlate with projection penetration to these highly vascularised regions, suggesting extravasation was not caused by direct puncture of blood vessels. Biomarker extravasation was also induced by dynamic application of flat control surfaces, and varied with the impact velocity, further supporting this conclusion. The extravasated protein distribution correlated well with regions of high mechanical stress generated during insertion, quantified by finite element models. Using this approach to induce extravasation prior to microprojection array-based biomarker capture, anti-influenza IgG was captured within a 2 min application time, demonstrating that extravasation can lead to rapid biomarker sampling and significantly improved microprojection array capture efficiency. These results have broad implications for the development of transdermal devices that deliver to and sample from the skin. PMID- 26826792 TI - [Staff accreditation in parenteral nutrition production in hospital pharmacy]. AB - OBJECTIVES: This work aims to provide staff accreditation methodology to harmonize and secure practices for parenteral nutrition bags preparation. METHODS: The methodology used in the present study is inspired from project management and quality approach. Existing training supports were used to produce accreditation procedure and evaluation supports. RESULTS AND DISCUSSION: We first defined abilities levels, from level 1, corresponding to accredited learning agent to level 3, corresponding to expert accredited agent. Elements assessed for accreditation are: clothing assessment either by practices audit or by microbiologic test, test bags preparation and handling assessment, bag production to assess aseptic filling for both manual or automatized method, practices audit, number of days of production, and non-conformity following. At Angers Hospital, in 2014, production staff is composed of 12 agents. Staff accreditation reveals that 2 agents achieve level 3, 8 agents achieve level 2 and 2 agents are level 1. We noted that non-conformity decreased as accreditation took place from 81 in 2009 to 0 in 2014. CONCLUSION: To date, there is no incident due to parenteral bag produced by Angers hospital for neonatal resuscitation children. Such a consistent study is essential to insure a secured nutrition parenteral production. This also provides a satisfying quality care for patients. PMID- 26826790 TI - Matrix rigidity differentially regulates invadopodia activity through ROCK1 and ROCK2. AB - ROCK activity increases due to ECM rigidity in the tumor microenvironment and promotes a malignant phenotype via actomyosin contractility. Invasive migration is facilitated by actin-rich adhesive protrusions known as invadopodia that degrade the ECM. Invadopodia activity is dependent on matrix rigidity and contractile forces suggesting that mechanical factors may regulate these subcellular structures through ROCK-dependent actomyosin contractility. However, emerging evidence indicates that the ROCK1 and ROCK2 isoforms perform different functions in cells suggesting that alternative mechanisms may potentially regulate rigidity-dependent invadopodia activity. In this study, we found that matrix rigidity drives ROCK signaling in cancer cells but that ROCK1 and ROCK2 differentially regulate invadopodia activity through separate signaling pathways via contractile (NM II) and non-contractile (LIMK) mechanisms. These data suggest that the mechanical rigidity of the tumor microenvironment may drive ROCK signaling through distinct pathways to enhance the invasive migration required for cancer progression and metastasis. PMID- 26826793 TI - [Management of outpatient medications in care units: An audit of clinical practices]. AB - OBJECTIVES: To assess the outpatient medication management in care units two years after the release of an institutional procedure. To assess the patients' satisfaction with their treatment and with the information transmitted by healthcare professionals. METHODS: An audit of clinical practices was conducted in 23 units of our universitary hospital - general, surgery, emergency departments. Questionnaires were developed and validated by an institutional working group and were composed of three themes: management of the outpatient medication at the admission, awareness of tools and information transmission. Two physicians (a senior and a resident), a registered nurse, a head nurse and a patient were interviewed. RESULTS: Eighty-one medical and paramedical team members and 21 patients were interviewed for the study. According to statements collected, the procedure was unknown by 100% of the interviewed surgeons and 69% of the interviewed physicians. The practices being used by the medical units were more in line with recommendations than the surgery units. Among the patients interviewed, 19 (86%) were satisfied with the information they received during their hospitalization and 4 (19%) managed their own medication treatment with the help of a nurse in only 36% of the cases according to their statements. CONCLUSIONS: The management of outpatient medications during hospitalization is representative of the difficulties to master the continuity of pharmaceutical care at the various transition points. Coordination and cooperation between the different healthcare professionals and patients are the major key success to ensure an optimized healthcare procedure. PMID- 26826794 TI - Cesium cation templated selective synthesis of a "cone-shaped" sugar macrotricyclic cryptand: A dual anion-cation molecular recognition of potassium tartrate. AB - Cesium templated Staudinger-aza-Wittig tandem reaction (S.A.W.) has been used in the synthesis of a bis-diazacrown-bis-cellobiosyl-tetra-ureido cryptand. A novel macrotricyclic compound having a "cone-shaped" configuration was selectively obtained. Additionally, first results on potential recognition properties of the cryptand are also given. PMID- 26826795 TI - Histone variants: nuclear function and disease. AB - Histone variants have emerged as important contributors to the regulation of chromatin structure and therefore of almost all DNA-based processes. Hence, these specialized proteins play important roles in transcriptional regulation, cell cycle progression, DNA repair, chromatin stability, chromosome segregation and apoptosis. Due to their evident biological significance, it is not surprising that mutations or the deregulation of their expression levels can have severe implications for cellular functions that ultimately might contribute to or even drive disease development, most notably cancer. Besides the histones themselves, their respective chaperone/remodeling complexes needed for precise variant chromatin deposition, are consequently frequent targets in neoplasms and diverse diseases. In this review, we briefly summarize current understanding on the function of human/mammalian histone variants and their regulatory networks and highlight their roles in cancer development. PMID- 26826796 TI - The Significance of Mutualistic Phages for Bacterial Ecology and Evolution. AB - Bacteria and phages have traditionally been viewed as 'antagonists'. However, temperate phages can transfer genes, which can broaden their bacterial hosts' metabolic repertoire, confer or enhance virulence, or eliminate competing organisms, and so enhance bacterial fitness. Recent evidence shows that phages can also promote biofilm formation leading to population-level benefits for their bacterial hosts. Here, we provide a perspective on the ecological and evolutionary consequences for the bacteria interacting with phages, when phage and host interests are aligned. Furthermore, we examine the question whether bacterial hosts can lower immune barriers to phage infection, thereby facilitating infection by beneficial phages. Taking recent evidence together, we suggest that in many cases temperate phages are to be considered as being mutualistic as well as parasitic, at the same time. PMID- 26826797 TI - Interpretation of Breast MRI Utilizing the BI-RADS Fifth Edition Lexicon: How Are We Doing and Where Are We Headed? AB - The Breast Imaging Reporting and Data System (BI-RADS) was first initiated in the late 1980s in order to standardize reporting, improve report organization, and to monitor outcomes for more clear, concise, and uniform communication of breast imaging findings. In the BI-RADS 5th edition, several changes and new additions have been made to the magnetic resonance imaging (MRI) lexicon, reflecting increased utilization and availability of breast MRI in clinical practice. Understanding the role and appropriate utilization of breast MRI and the BI-RADS lexicon could help with interpretation and effective communication of MRI findings as well as preparing for incorporation of more advanced imaging techniques. In this comprehensive review of the changes and new descriptors in the MRI section of the fifth edition of BI-RADS with pictorial examples, the reader would be able to achieve improved understanding of the MRI BI-RADS lexicon and its appropriate applications. PMID- 26826798 TI - Literature review of teaching skills programs for junior medical officers. AB - OBJECTIVE: The aim of this review was to assess the current evidence regarding the efficacy of teaching skills programs for junior medical officers. We aimed to compare and contrast these results with findings from previous literature reviews, the last of which were published in 2009. METHODS: In order to capture studies since the last published literature reviews, five databases and grey literature were searched for publications from January 2008 to January 2015. A search for literature reviews without using the timeframe limitation was also performed. RESULTS: The search from January 2008 to January 2015 resulted in the inclusion of 12 studies. Five systematic reviews of the topic were found which included 39 individual studies that were also analysed. Nearly all studies reported positive effects. Twenty nine studies reported change in attitudes, 28 reported modification in knowledge, 28 reported change in behaviour, 6 reported change in the organisation and two reported change in program participant's students. There were substantial threats of bias present. CONCLUSIONS: The literature reviewed demonstrated many positive effects of teaching skills programs, which supports their utilization. However, high level outcomes need to be evaluated over longer periods of time to establish their true impact. An organisation specific approach to these programs needs to occur using sound course design principles, and they need to be reported in evaluation trials that are designed with robust methodology. PMID- 26826799 TI - Design and synthesis of a novel class of carbonic anhydrase-IX inhibitor 1-(3 (phenyl/4-fluorophenyl)-7-imino-3H-[1,2,3]triazolo[4,5d]pyrimidin 6(7H)yl)urea. AB - Carbonic anhydrase IX (CAIX) is a promising target in cancer therapy especially in the case of hypoxia-induced tumors. The selective inhibition of CA isozymes is a challenging task in drug design and discovery process. Here, we performed fluorescence-binding studies and inhibition assay combined with molecular docking and molecular dynamics (MD) simulation analyses to determine the binding affinity of two synthesized triazolo-pyrimidine urea derived (TPUI and TPUII) compounds with CAIX and CAII. Fluorescence binding results are showing that molecule TPUI has an excellent binding-affinity for CAIX (kD=0.048MUM). The TPUII also exhibits an appreciable binding affinity (kD=7.52MUM) for CAIX. TPUI selectively inhibits CAIX as compared to TPUII in the 4-NPA assay. Docking studies show that TPUI is spatially well-fitted in the active site cavity of CAIX, and is involve in H-bond interactions with His94, His96, His119, Thr199 and Thr200. MD simulation studies revealed that TPUI efficiently binds to CAIX and essential active site residual interaction is consistent during the entire simulation of 40ns. These studies suggest that TPUI appeared as novel class of CAIX inhibitor, and may be used as a lead molecule for the development of potent and selective CAIX inhibitor for the hypoxia-induced cancer therapy. PMID- 26826800 TI - Quantitative structure-hydrophobicity relationships of molecular fragments and beyond. AB - Quantitative structure-property relationship (QSPR) models were firstly established for the hydrophobic substituent constant (piX) using the theoretical descriptors derived solely from electrostatic potentials (EPSs) at the substituent atoms. The descriptors introduced are found to be related to hydrogen bond basicity, hydrogen-bond acidity, cavity, or dipolarity/polarizability terms in linear solvation energy relationship, which endows the models good interpretability. The predictive capabilities of the models constructed were also verified by rigorous Monte Carlo cross-validation. Then, eight groups of meta- or para-disubstituted benzenes and one group of substituted pyridines were investigated. QSPR models for individual systems were achieved with the ESP derived descriptors. Additionally, two QSPR models were also established for Rekker's fragment constants (foct), which is a secondary-treatment quantity and reflects average contribution of the fragment to logP. It has been demonstrated that the descriptors derived from ESPs at the fragments, can be well used to quantitatively express the relationship between fragment structures and their hydrophobic properties, regardless of the attached parent structure or the valence state. Finally, the relations of Hammett sigma constant and ESP quantities were explored. It implies that sigma and pi, which are essential in classic QSAR and represent different type of contributions to biological activities, are also complementary in interaction site. PMID- 26826802 TI - Oogenesis in the Bemisia tabaci MEAM1 species complex. AB - The whitefly Bemisia tabaci MEAM1 species complex has invaded several parts of the world in the past 30 years and replaced native whitefly populations in the invaded regions, including certain areas of China. One of the possible reasons for the invasion is that MEAM1 whiteflies are more fecund than native species. However, the factors that affect the reproduction of the B. tabaci cryptic species are not clearly known. The regulation of oogenesis is thought to be one of the essential processes for egg formation and ovary development and could affect its population dynamics. In this study, the ovariole structure and oogenesis of the MEAM1 species complex was examined using light and transmission electron microscopy. Telotrophic ovarioles were observed in the MEAM1 species complex. Each ovariole had two well defined regions: the tropharium and the vitellarium. The tropharium always had more than ten trophocytes. The development of a single oocyte in the vitellarium has four phases: oocyte formation, previtellogenesis, vitellogenesis and choriogenesis. Two arrested oocytes, follicular cells and uncompleted oocytes were separated from the tropharium by microtubule and microfilaments. Early previtellogenesis oocytes absorbed nutrients and endosymbiont bacteria through a nutritive cord. However, the vitellogenesis of oocytes transmitted Vg through both the nutritive cord and the space between follicular cells. Each mature oocyte with deposited yolk proteins had only one bacteriocyte and was surrounded by a single layer of follicular cells. The oogenesis in the B. tabaci MEAM1 species complex concluded with the differentiation of oocytes, the transport of yolk and endosymbionts as well as the development and maturation of oocytes. This result provides important information that further defines the regulation of oogenesis in the B. tabaci complex. PMID- 26826801 TI - In silico study of subtilisin-like protease 1 (SUB1) from different Plasmodium species in complex with peptidyl-difluorostatones and characterization of potent pan-SUB1 inhibitors. AB - Plasmodium falciparum subtilisin-like protease 1 (SUB1) is a novel target for the development of innovative antimalarials. We recently described the first potent difluorostatone-based inhibitors of the enzyme ((4S)-(N-((N-acetyl-l-lysyl)-l isoleucyl-l-threonyl-l-alanyl)-2,2-difluoro-3-oxo-4-aminopentanoyl)glycine (1) and (4S)-(N-((N-acetyl-l-isoleucyl)-l-threonyl-l-alanylamino)-2,2-difluoro-3-oxo 4-aminopentanoyl)glycine (2)). As a continuation of our efforts towards the definition of the molecular determinants of enzyme-inhibitor interaction, we herein propose the first comprehensive computational investigation of the SUB1 catalytic core from six different Plasmodium species, using homology modeling and molecular docking approaches. Investigation of the differences in the binding sites as well as the interactions of our inhibitors 1,2 with all SUB1 orthologues, allowed us to highlight the structurally relevant regions of the enzyme that could be targeted for developing pan-SUB1 inhibitors. According to our in silico predictions, compounds 1,2 have been demonstrated to be potent inhibitors of SUB1 from all three major clinically relevant Plasmodium species (P. falciparum, P. vivax, and P. knowlesi). We next derived multiple structure based pharmacophore models that were combined in an inclusive pan-SUB1 pharmacophore (SUB1-PHA). This latter was validated by applying in silico methods, showing that it may be useful for the future development of potent antimalarial agents. PMID- 26826803 TI - Patient information in orthopedic and trauma surgery. Fundamental knowledge, legal aspects and practical recommendations. AB - Providing information to surgery patients is a form of health-care governed by clearly defined therapeutic and medicolegal rules, and in particular in France by the Act of March 4, 2002 and the Code of Good Practice. The patient's right to information is implemented in a face-to-face consultation, which should be fully codified, and in a specific clinical examination, followed by information regarding the affected organ, pathology, treatment options, possible surgery, and the preconditions, risks and results associated with the procedure. Information should be personalized and as complete as possible, communicating the state of knowledge as validated by scientific societies and medical institutions. State of the art technology (dedicated website, on-line information suites, etc.) is indispensable but needs to be mastered and to adhere to the guidelines of the Council of the National Order of Medicine. Information traceability, the retraction period and proof of content of the information are essential. A signed document delivered in an informative atmosphere optimizes the exercise. Patient information is an ethical and medicolegal obligation, but above all is the expression and demonstration of the health-care potential of the practitioner and our contribution to reducing the information gap, reinforcing the cement holding our society together. PMID- 26826804 TI - Effects of third fragment size and displacement on non-union of femoral shaft fractures after locking for intramedullary nailing. AB - BACKGROUND: The femoral shaft fractures with large fragments makes anatomical reduction challenging and often results in non-union. In some studies, the degree of fragment displacement was reported to have affected non-union, but the association between the one fragment size and degree of displacement has not been fully clarified. Therefore we performed a retrospective study to assess: (1) the more influential factor of non-union: the degree of fragment displacement, or the fragment size? (2) the non-union rates according to different sizes and degrees of displacement. HYPOTHESIS: The degree of displacement is the more potent factor of non-union than the third fragment size in femoral shaft fractures. PATIENTS AND METHODS: We assessed retrospectively 64 cases, which could be followed up for longer than one year. Fragments were divided according to the length of their long axis into three groups: group A (0-3.9cm), (n=21); group B (4-7.9cm), (n=22); group C (8cm or more), (n=21). Fragment displacement was also assessed in the proximal (P) or distal (D) end to the nearest cortex of the femoral shaft, and divided into the following groups: group P1 (n=44) or D1 (n=47), (0-9mm); group P2 (n=10) or D2 (n=11), (10-19mm); group P3 (n=7) or D3 (n=3), (20-29mm); and group P4 (n=3) or D4 (n=3), (30mm or more). RESULTS: The bone union rate was 86% in the small (less than 8cm) fragment groups and 71% in the large (8cm or more) fragment group (P=0.046). With respect to the degree of displacement, the union rate was lower (P=0.001) and the average union time was longer (P=0.012) in the 20mm or more group for both the proximal fragment part and the distal fragment part (P=0.002, P=0.014). A logistic regression analysis underlined the displacement in the proximal site (OR: 0.298, 95% CI: 0.118-0.750) as in the distal site (OR: 0.359, 95% CI: 0.162-0.793) as a larger effect on union rate than the fragment size that as no effect in logistic regression (OR 3.8, 95% CI: 0.669-21.6). CONCLUSION: Non-union develops significantly more frequently in femoral shaft fractures with fragments 8cm or longer or when the displacement in the proximal area is 20mm or greater and 10mm or greater in the distal area during the intramedullary nailing procedure. Regarding union rate, the degree of displacement has more influence than the third fragment size in femoral shaft fractures. LEVEL OF EVIDENCE: IV, retrospective cohort study. PMID- 26826805 TI - The effects of relocation and level of affectedness on mood and anxiety symptom treatments after the 2011 Christchurch earthquake. AB - In this longitudinal study, we compare the effects of different types of relocation and level of affectedness on the incidence and relapse of mood and anxiety symptom treatments identified by publicly funded care or treatment one year before and one and two years after the '2011 Christchurch earthquake' in New Zealand. Based on a subset of Christchurch residents from differently affected areas of the city identified by area-wide geotechnical land assessments (no to severe land damage) 'stayers', 'within-city movers', 'out-of-city movers' and 'returners' were identified to assess the interaction effect of different levels of affectedness and relocation on the incidence and relapse of mood and anxiety symptom treatments over time. Health and sample information were drawn from the New Zealand Ministry of Health's administrative databases allowing us to do a comparison of the pre-/post-disaster treatment status and follow-up on a large study sample. Moving within the city and returning have been identified as general risk factors for receiving care or treatment for mood or anxiety symptoms. In the context of the 2011 Christchurch earthquake, moving within the city showed a protective effect over time, whereas returning was a significant risk factor in the first post-disaster year. Additionally, out-of-city movers from minor, moderately or severely damaged Christchurch's plain areas were identified as especially vulnerable two years post-disaster. Generally, no dose response relationship between level of affectedness and mood or anxiety symptom treatments was identified, but the finding that similarly affected groups from the city's plain areas and the more affluent Port Hills showed different temporal treatment trends highlights the importance of including socio-economic status in exposure assessment. High-risk groups included females, older adults and those with a pre-existing mental illness. Consequently, mental health intervention programs should target these vulnerable groups, as well as out-of-city movers from affected areas in the long run. PMID- 26826806 TI - 'Signposts on the journey'; medication adherence and the lived body in men with Parkinson's disease. AB - Adherence to medication has been identified as a key issue in the treatment of many chronic illnesses, however such a perspective fails to account for the lived experience of medication usage and its effects on the body as lived. Parkinson's Disease, a neurological disease predominantly affecting movement and mobility, and which is treated via a wide range of medications provides a useful opportunity to explore experiences of medication usage in chronic illness. Reporting on findings of a study exploring men's experience of living with Parkinson's Disease, this paper adopts a lived body perspective to explore lived experiences of medication usage and adherence in PD. Findings are reported from 30 narrative in depth interviews with 15 men of various ages living with Parkinson's disease of mild to severe intensity. Findings first discuss PD's effects on men's sense of the lived body, in which a fluctuating embodiment is linked to medication regimes and their bodily effects. Second, as PD disrupts the body's place with the everyday and habitual experience of lived time, medication regimens come to place new structures upon the men's everyday experience of time. Finally, the paper explores the role medications play in men's attempts to create and sustain narratives for the individual progression of their illness, and how these narratives differ from clinical narratives associated with PD's treatment. This paper concludes by discussing debates around adherence to medication within the treatment of PD and the need to consider lived experience of medication usage and their effects at the level of the lived body. PMID- 26826807 TI - Eliciting human values for conservation planning and decisions: A global issue. PMID- 26826808 TI - The effect of zinc supplementation on the urinary excretion of elements in female athletes. AB - This study was carried out to find out how oral zinc supplementation to elite athletes affects the element changes in the urine. The study registered 10 female athletes who were on the women's volleyball team of Gazi University Sports Club and whose mean age, weight, and height were 14.2+/-0.42 years, 59.8+/-7.79kg and 173.6+/-6.15 cm. The study protocol was approved by the local ethics committee. The athletes who continued their daily routine training sessions (6 days/week) were supplemented with 220mg/day oral zinc sulfate for 4 weeks. In order to induce exhaustion, the subjects were put to a 20-meter shuttle run test before and after supplementation. A total, 7 times urine samples were collected follows as pre and post exercise before the start of the experiment and at the end (4 times), at the end of first, second and third week (3 times). Urinary levels of magnesium, phosphorus, and calcium (mg/dl), as well as zinc, copper, and selenium (MUg/dl) were analyzed in the atomic emission device (ICP-MS). Arithmetic means and standard errors of the data were calculated. Kruskal Wallis test was used to determine differences between weeks. Values for which p<0,05 were considered significant. When compared to resting values, urinary excretion of copper and selenium decreased in exercise (p<0,05), but increased with zinc supplementation (p<0,05). Pre- and post-supplementation exercise resulted in reduced urinary zinc excretion (p<0,05). Zinc supplementation increased urinary zinc excretion in one week intervals over the course of 4 weeks (p<0,05), and reduced selenium levels (p<0,05). When zinc is supplemented to athletes, the relation between the duration and dose of supplementation is important. The results of the study indicated that zinc does not have any negative effect on the urinary excretion of the concerned elements. It can thus be concluded that athletes may benefit from zinc support. PMID- 26826809 TI - Effects of spironolactone towards rabbit atrial remodeling with rapid pacing. AB - This study aimed to observe the effects of spironolactone towards the rabbit atrial remodeling with rapid atrial pacing (RAP). 30 rabbits were randomly divided into control group, RAP group and spironolactone group, with 10 rabbits in each group. RAP was performed at the speed of 800 beats/min for 8 h, atrial effective refractory period (AERP) was determined before and at the 1(st), 2(nd), 4(th), 6(th) and 8(th) of the pacing, the expressions of atrial muscular calcium channel alpha1C subunit and beta1 subunit mRNA were performed the RT-PCR detection, and ultrastructural changes of atrial myocytes were observed. AERP of RAP group shortened, with poor frequency adaptability; the expressions of calcium channel alpha1C subunit and beta1 subunit mRNA decreased 22% and 26%, respectively, when compared with the control group; ultrastructure of atrial myocytes changed significantly. AERP of spironotlactone group shortened less that RAP group, and the frequency adaptability was maintained, the decreased expressions of calcium channel alpha1C subunit and beta1 subunit mRNA significantly reduced. RAP could cause atrial remodeling, while spironolactone could inhibit RAP-induced atrial remodeling. PMID- 26826810 TI - Development of cetyl dimethicone based water-in-oil emulsion containing botanicals: Physical characteristics and stability. AB - The aim of current research was to develop a water-in-oil emulsion containing grape seed extract for application in cosmeceuticals. Finally grinded dried grape seeds powder was extracted with hydro alcoholic mixture. Emulsions consisting of different concentrations of cetyl dimethicone (Abile EM90), the nonionic emulsifier, liquid paraffin as oily phase and water as aqueous phase were developed. Color, odor, pH, viscosity, liquefaction, phase separation, centrifugation and thermal stability of the formulated emulsions were observed at various storage temperatures i.e. 8+/-0.5 degrees C, 25+/-0.5 degrees C, 40+/-0.5 degrees C and 40 degrees C+/-0.5 degrees C with 70% RH. The stable formulation consist of 16% mineral oil, 4% of ABIL EM 90((r)), 4% grape seeds extract, 1% rose oil and 75% distilled water. All the results derived from this study showed good stability over the three months study period which indicates w/o emulsion can be used as carrier of 4% grape seeds extract to enhance desired effects when applied topically. PMID- 26826811 TI - Counter effects of N. Sativa L. and P. ovate L. on indicative markers of non alcoholic fatty liver disease. AB - The broad spectrum of non-alcoholic fatty liver disease (NAFLD) diseases ranges from simple liver inflammation to steatosis, leading to fibrosis and cirrhosis. Four groups of weaning (30g) Rattus norvegicus were designated as W-0, W-I, W-II and W-III. For sixteen weeks group W-0 was given standard pallet diet, group I consumed diet "A" (20% fat Sucrose + 33% tea whitener + 34% ground pallet diet +13% water), group W-II was fed on diet "B" (50g Nigella sativa seeds/kg of A) and group W-III was provided with diet "C" (50g Plantago ovata husks /Kg of A). The analysis of CBC, LFTs, and Lipid profile revealed that there were highly significant changes (P<0.001) in the MCV, PLT, Hb, MCH, MCHC, RBC, RDW%, WBC, MPV, Triglycerides, cholesterol, LDL and the significant alterations (P<0.01) in albumin, AST, bilirubin, AST/ALT, HDL and cholesterol/HDL were observed in the experimental groups when compared with control by using one way ANOVA. We concluded that high-energy diet can alter the blood profile. Moreover fat plummeting agents have counter impact on the hematology as well as serology of diet induced NAFLD in R. norvegicus. PMID- 26826812 TI - HPTLC analysis and in-vitro antioxidant, anti-inflammatory and anti-diabetic activities of ethanol extract of leaves of Actinodaphne madraspatana Bedd. AB - The aim of the present study was to develop the HPTLC fingerprint and to evaluate the in-vitro antioxidant, anti-inflammatory and anti-diabetic activities of ethanol extract of leaves of Actinodaphne madraspatana Bedd (A. madraspatana). HPTLC fingerprint analysis of ethanol extract was investigated by win CATS planar chromatography. The antioxidant activity was evaluated by the various antioxidant assays, such as total antioxidant, reducing power, DPPH radical scavenging, hydrogen peroxide scavenging and hydroxyl radical scavenging. The antioxidant activity was compared to standard drug ascorbic acid. In-vitro anti-inflammatory activity was evaluated by inhibition of albumin denaturation assay using aspirin as a standard drug. In-vitro anti-diabetic activity was evaluated by alpha amylase inhibition assay using acarbose as a standard drug. The HPTLC fingerprint of ethanol extract has shown six peaks, which indicate the presence of six different phytocomponents. The in-vitro antioxidant, anti-inflammatory and anti diabetic activities of ethanol extract of plant leaves increased with the increasing of concentration. The result revealed that extract in all the concentration showed the in-vitro antioxidant, anti-inflammatory and anti diabetic activities compared to standard drugs. The ethanol extract of leaves of A. madraspatana has a potential effect as an antioxidant, anti-inflammatory and anti-diabetic in all the tested in-vitro methods. PMID- 26826813 TI - Brewers' rice attenuated aberrant crypt foci developing in colon of azoxymethane treated rats. AB - Brewers' rice is one of abundant agricultural waste products in the rice industry. The present study is designed to investigate the potential of brewers' rice to inhibit the development of aberrant crypt foci (ACF) in colon of azoxymethane (AOM)-treated rats. The effects on the attenuation of hepatic toxicity and kidney function enzymes were also evaluated. Male Sprague-Dawley rats were randomly divided into five groups: (G1) normal; (G2) AOM alone; and (G3), (G4), and (G5), which were AOM fed with 10%, 20%, and 40% (w/w) of brewers' rice, respectively. The rats in group 2-5 were injected intraperitoneally with AOM (15 mg/kg body weight) once weekly for two weeks. After 8 weeks of treatment,the total number of ACF/colon and the number of ACF in the distal and middle colon were significantly reduced in all treatment groups compared to G2 (p<0.05). Brewers' rice decreased the number of ACF with dysplastic morphology in a dose-dependent manner. Alkaline phosphatase (ALP) level in G5 was significantly lower compared to the G2 (p<0.05). In conclusion, this study found the potential value of brewers' rice in reducing the risk of cancer susceptibility in colon. PMID- 26826814 TI - Biological activities of some Acacia spp. (Fabaceae) against new clinical isolates identified by ribosomal RNA gene-based phylogenetic analysis. AB - Nowadays,most of the pathogenic bacteria become resistant to antibiotics. Therefore,the pharmaceutical properties of the natural plant extracts have become of interest to researchers as alternative antimicrobial agents. In this study,antibacterial activities of extract gained from Acacia etbaica, Acacia laeta, Acacia origena and Acacia pycnantha have been evaluated against isolated pathogenic bacteria (Strains MFM-01, MFM-10 and AH-09) using agar well diffusion methods.The bacterial strains were isolated from infected individuals,and their exact identification was detected on the basis of 16S rRNA gene amplification and sequence determination. Alignment results and the comparison of 16 SrRN A gene sequences of the isolates to 16 SrRN A gene sequences available in Gen Bank data base as well as the phylogenetic analysis confirmed the accurate position of the isolates as Klebsiella oxytoca strain MFM-01, Staphylococcus aureus strain MFM-10 and Klebsiella pneumoniae strain AH-09. Except for cold water, all tested solvents (Chloroform, petroleum ether, methanol, diethyl ether, and acetone) showed variation in their activity against studied bacteria. GC-MS analysis of ethanol extracts showed that four investigated Acacia species have different phyto components. Eight important pharmaceutical components were found in the legume of Acacia etbaica, seven in the legume of Acacia laeta, fifteen in the legume of Acacia origena and nine in the leaves of Acacia pycnantha. A dendrogram was constructed based on chemical composition, revealed that Acacia laeta is more closely related to Acacia etbaica forming on eclade, whereas Acacia origena less similar to other species. Our results demonstrated that, investigated plants and chemical compounds present could be used as promising antibacterial agents. PMID- 26826815 TI - Ethanolic extract of Nigella sativa protects Fe(II) induced lipid peroxidation in rat's brain, kidney and liver homogenates. AB - The study describes the effect of ethanolic extract of Nigella sativa against Fe(II) induced lipid peroxidation. Basal and Fe(II) induced thiobarbituric acid reactive species (TBARS) production was significantly inhibited by the ethanolic extract of Nigella sativa at 25-200 MUg/ml. Our data revealed that the extract has high DPPH radical scavenging activity at highest tested concentrations. The extract significantly chelated Fe(II) and scavenged hydroxyl (OH) radical at 25 200MUg/ml concentration. The nutritional analysis was performed and carbohydrate, fats, fiber, protein, moisture and ash content were measured in the studied extract. The phytochemical analysis confirmed the presence of alkaloid, carbohydrate & sugar, glycosides, phenolic compounds, flavonoids, protein and amino acid, phytosterols, tannins, gum and mucilage. The extract also showed significant antimicrobial activities against 10 bacterial strains i.e. Salmonella typhi, Bacillus subtilis, Bacillus cereus, Klebsiella pneumonia, Escheria coli, Xanthomonas, Salmonella heidelberg, Staphylococcus aureus, Clostridium and Escheria coli (human) and 5 fungal strains i.e. Aspergillus niger, Entomola, Aspergillus flavus, Alternaria alternata and Penicillium. This study confirms the potential antioxidant and antimicrobial activities of ethanolic extract of Nigella sativa which can be considered not only as a diet supplement but can be used against a variety of free radical induced damage diseases. PMID- 26826816 TI - Report: Qadir test. AB - The present diagnostic tests for cancers are expensive and are not accessible by poor. Therefore, it was necessary to explore a diagnostic test accessible by general public. Plasma lipid profile is decreased in all the cancers except in breast cancer, where HDL-cholesterol is decreased while the other lipids are increased. Therefore, plasma lipid profile may be used as diagnostic test for malignancy. As general diagnostic procedures, these laboratory parameters (plasma lipids) should also be co-related with the clinical symptoms of the patient and other diagnostic tools. PMID- 26826817 TI - Report: Antioxidant and hypoglycemic activity of strawberry fruit extracts against alloxan induced diabetes in rats. AB - The strawberries (Fragaria x ananassa) of Rosaceae family are an accomplished source of bioactive compounds such as ascorbic acid and diverse range of polyphenols including anthocyanins, phenolic acids, flavonols, ellagitannins etc. These phenolic compounds classify strawberry as an important health promoting food. Strawberries are proved to have potent antioxidant capacity in various in vitro assay systems. The in vivo beneficial effects are getting explored against various ailments including cancer, metabolic syndrome, and cardiovascular diseases. The present research study was designed to analyze the effect of strawberry fruit extracts (water and methanol) against alloxan induced hyperglycemia in albino rats of Wister strain. Upon alloxan (150mg/kg body weight) induction, the diabetic animals showed marked increase in the values of plasma glucose, urea, uric acid, creatinine and concomitant decrease in body weight and plasma insulin level. The oral administration of strawberry extracts for 45 days in diabetic animals reversed the biochemical changes significantly (P0.05) to near normal. Furthermore, the restoration of body weight loss was also observed. The results suggest that the strawberry extract has effective hypoglycemic activity against alloxan diabetes. The poly phenolic antioxidant contents of the strawberry fruit extracts are responsible for the observed biological effect. PMID- 26826818 TI - Anti-ulcer activity of the aqueous extract of Melastoma malabathricum L. leaf in rats. AB - Melastoma malabathricum L. Smith (Melastomaceae) has been used in the Malay traditional culture to treat ulcer-based ailments.The objective of the present study was to investigate the potential anti-ulcer effect of aqueous extract of M. malabathricum leaves (AEMM) using ethanol- and indomethacin-induced gastric ulcer models in rats. Rats were divided into ten groups (n=6) and received DMSO (10%; negative group), ranitidine (100mg/kg; positive group) or AEMM (50, 250 and 500mg/kg) orally for 7 days and on the 8(th) day subjected to the respective gastric ulcer models. The stomachs were collected and subjected to macroscopic and microscopic analysis. At all groups tested, the AEMM exerted significant (p<0.05) anti-ulcer effect only against the ethanol-induced gastric ulcer model. The percentage of anti-ulcer for the 50-500mg/kg AEMM ranging between 50-82%, respectively. The macroscopic observations were supported by histological findings. In conclusion, AEMM exhibits potential anti-ulcer activity attributed to its previously proven high flavonoids content and antioxidant activity. PMID- 26826819 TI - In vitro activity of antimicrobial agents against streptococcus pyogenes isolated from different regions of Khyber Pakhtun Khwa Pakistan. AB - The present study investigates the antibiotic resistance of S. pyogenes of 600 isolates collected from different body parts including throat and sputum were analyzed for their antimicrobial susceptibility to 5 antibiotics using the Kirby Bauer disc diffusion method. Based on different identification tests including, gram staining, beta hemolysis, catalase test and bacitracin sensitivity test, a total of 138 isolates were confirmed as S. pyogenes. The prevalence of S. pyogenes was 80% in sore throat and 29% in sputum samples. These isolates were further tested for antibiotics resistance using disk diffusion method. Out of 138 isolates, 49.27% isolates showed resistance towards cefixime, 28.98% towards cefotaxime and 17.39% towards ciprofloxacin, 17.39% towards ampicillin, 17.39% towards erythromycin, 15.94% towards streptomycin, 0.724% isolates towards chloromphenicol and 0% towards penicillin. Among the resistant isolates of S. pyogenes, 60.71% showed resistance towards cefixime, 57.14% towards ciprofloxacin, 57.14% towards streptomycin, 50% towards erythromycin and 25% towards cefotaxime. PMID- 26826820 TI - Depletion of GSH in human blood plasma and cytosolic fraction during cadmium toxicity is temperature and pH dependent. AB - Toxicities of heavy metals is a burning issue and a topic of interest among the toxicologists throughout the world. Metals are always in use of man since long but in recent years the use of cadmium has increased in the form of various cadmium compounds such as cadmium compounds as stabilizers in plastic pipe industries and in the preparations of different alloys etc. Cadmium is even used in phosphate fertilizers and thus comes directly or indirectly in contact with human eatables like crops, vegetables and fruits. Once it is absorbed it affects almost all the organs and systems of human body especially blood components and kidneys. Always the chemical reactions of different chemicals are dependent on some influential factors, among these factors the effect of pH and temperature of the media in which these chemicals interact with each other are very much important. Keeping in view this fact we have evaluated the effect of cadmium nitrate tetra hydrate on GSH of human plasma and cytosolic fraction. Estimation of thiol was done by Ellman's modified method and was found that the interaction of cadmium nitrate tetra hydrate and GSH of these blood components was more at a pH and temperature, which were near to physiological pH and temperature of human body. This fact was proved as the estimated thiol concentration left after the interaction of cadmium nitrate tetra hydrate and thiol of these blood components was minimum at pH and temperature near to human blood pH and temperature. We concluded that the possible reason for depletion of GSH of these blood components was conversion of GSH into Cd(SG) (2) and/or GSSG formation. PMID- 26826821 TI - Antimicrobial and toxicological studies on fruit pulp of Citrullus colocynthis L. AB - The methanolic extract of dried fruit pulp of Citrullus colocyn this (Cucurbitaceae) has been studied with respect to antimicrobial and toxicological properties. The antimicrobial profile was investigated against thirty bacterial isolates (10 Gram +ve and 20 Gram-ve) and five fungal species. None of the bacterial or fungal culture used in the study showed sensitivity against the extract. Acute toxicity studies carried out in Albino mice NMRI indicated the highly toxic nature of the colocynth. A very significant decrease in body weight of test animals was noted at P<0.05. The LD(50) was calculated as 1000mg/kg body weight. Within four days of experimentation mortality was 100%. Histopathological studies confirmed the toxic nature of extract. Gross changes in histology of Heart, Liver and Kidneys were noted. Section of spleen did not exhibit any abnormality. PMID- 26826822 TI - Vasorelaxant effect of essential oil isolated from Nigella sativa L. seeds in rat aorta: Proposed mechanism. AB - The effect of the essential oil extracted from Nigella sativa (L.) seeds (Nigella oil) was investigated for its vasorelaxant activity on isolated rat aorta. Nigella oil at concentrations of 10-100 MUg/mL elicited a dose-dependent relaxation of the aorta, which was pre-contracted with noradrenaline (NA, 10(-6) M) or KCl (100mM). In the presence of Nigella oil (75 MUg/mL, the dose response curves to increasing concentrations of NA (10(-9) M to 10(-4)M) or KCl (10mM 100mM) were displaced downwards, indicating inhibition of the vasoconstrictive effect. This relaxation effect was independent of the presence of endothelium. In addition, the vasodilatory activity of the Nigella oil was not affected by pre treatment of the rings with N(G)-nitro-L-Arginine (an inhibitor of endothelial nitric oxide synthase; 0.1mM), suggesting that the vasorelaxant effect is not mediated by nitric oxide. Furthermore, pre-treatment of the rings with Nigella oil (75 MUg/mL suppressed the tension increment produced by increasing external calcium concentration (0.25 mM to 1.5mM). Tin conclusion, the essential oil extracted from Nigella sativa seeds produces smooth muscle relaxation, which is independent of endothelium and is not mediated by nitric oxide. The results also suggest that the vasorelaxing effect of the oil results from the blockade of both voltage-sensitive and receptor-operated calcium channels, and this may have therapeutic significance, in that Nigella oil may be useful as an antihypertensive agent in humans. PMID- 26826823 TI - Pharmacognostic studies on Taxus baccata L.: A brilliant source of Anti-cancer agents. AB - The present investigation was undertaken to establish standardization profile of Taxus baccata L. with the help of pharmacognostic parameters, which is not done before. T. baccata(Taxaceae), is native to Europe, is an evergreen needle-leaved tree, growing up to 28 m high. A large number of phytochemicals like taxoids viz. taxusin, baccatin, baccatin, lignans, flavanoids, steroids, paclitaxel and sugar derivatives have been isolated from it. For the treatment of different types of cancer like ovarian and breast cancers, Kaposi's sarcoma and lung cancers Paclitaxel (taxol) has been approved. Paclitaxel is also under clinical trial for remedy of number of other cancers in combination with other chemotherapeutic medications. Pharmacognostical and preliminary phytochemical screening of T. baccata will be useful to authenticate and avoid adulteration in the raw material. The diagnostic microscopic characters, physiochemical data and FTIR will be useful in the development of monograph. PMID- 26826824 TI - Effect of lipid extracts of Nigella sativa L. seeds on the liver ATP reduction and alpha-glucosidase inhibition. AB - Various extracts from the seeds of Nigella sativa have been used in traditional folk medicine to treat inflammation, liver disorders and arthritis. These seeds have been experimentally shown to possess antioxidant and hepatoprotective properties. Beside the hypoglycaemic and hypolipidemic effects, this study was carried out to evaluate, in vitro, toxicological effect of lipid extracts from the Nigella sativa seeds. The tested fractions were: (i) defatted methanolic extract, (ii) total lipid extract obtained by hexane extraction from methanolic extract and (iii) neutral and polar lipid fractions. The fractions were assessed, in vitro, for their inhibitory activity potential on the enzyme alpha-glucosidase as suppressing the enzyme activity is one among the therapeutic approaches to attenuate postprandial hyperglycemia. High inhibition of alpha-glucosidase by the two polar lipid fractions (F6 and F7) was reflected by their IC50 (0.51+/ 0.04mg/ml and 0.55+/-0.09mg/ml, respectively), compared to acarbose (0.53+/ 0.06mg/ml) and thymoquinone (0.65+/-0.05mg/ml). The hypoglycaemic effect of the polar lipid fraction of Nigella sativa could be explained by the inhibition of alpha-glucosidase, which is one of early steps of carbohydrate metabolism. Toxicological evaluation was investigated on precision-cut rat liver slices (PCLS). On PCLS, lipid extracts reduced ATP levels by 27 to 35%. Results indicate suggest that Nigella sativa extracts don't show a hepatoprotective effect against acetaminophen, but don't exhibit a major hepatotoxicity when tested alone. PMID- 26826826 TI - Biosynthesis, characterization and antimicrobial action of silver nanoparticles from root bark extract of Berberislycium Royle. AB - Various biological methods are being recognized for the fabrication of silver nanoparticles, which are used in several fields. The phytosynthesis of nanoparticles came out as a cost effective and enviro-friendly approach. When root bark extract of Berberis lycium was treated with silver ions, they reduced to silver nanoparticles, which were spherical, crystalline, size ranged from 10 100nm and capped by biomolecules. Synthesized silver nanoparticles were characterized by UV-visible spectroscopy, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), Transmission Electron Microscopy (TEM), X-Ray Diffraction (XRD) and Fourier Transform Infra Red Spectroscopy (FTIR). The plant mediated synthesized silver nanoparticles showed pronounced antimicrobial activities against both Gram negative bacteria (Escherichia coli, Klebseilla pneumoniae, Pseudomonas aeruginosa) and Gram positive bacteria (Staphylococcus aureus and Bacillus subtilis). The plant mediated process proved to be non-toxic and low cost contender as reducing agent for synthesizing stable silver nanoparticles. PMID- 26826825 TI - Ondansetron: A newer aspect of dose response relationship on ileal smooth muscles of rabbit. AB - There are several life threatening deadly diseases in our world but 'Cancer' out powers them all in recent years. Chemotherapy may be used on its own or an adjunct to other forms of therapy. Despite the advancement in cytotoxic drug therapy and supportive treatment almost 70% of patient suffer from chemotherapy induced nausea and vomiting (CINV). Ondansetron, a 5-HT(3) receptor antagonist has now become a gold standard in the treatment of chemotherapy induced nausea and vomiting. The central actions of ondansetron are well established but its peripheral actions are not well recognized. The aim of our study was to explore the peripheral actions of ondansetron. Experiments were performed in five groups (n=6) and ileal smooth muscles activity was recorded on power lab (USA). The effects of increasing concentrations of acetylcholine, serotonin & ondansetron alone was observed in first three groups. In the next two groups effects of acetylcholine and serotonin pretreated with fixed concentration (1ml) of ondansetron (10-pi M)were studied. The maximum response obtained by acetylcholine served as a control for our study. Maximum response with acetylcholine was taken as 100% and with serotonin was 177 percent of control. Cumulative dose response curve with ondansetron was triphasic. At 10-psiM it was 28.8%, whereas with 10 xiM the amplitude decreased to 16.87%, it reached to plateau at 10-pi M. Response of acetylcholine & serotonin was decreased to 57% and 78% respectively in the presence of fixed concentration of ondansetron (10-pi M). Ondansetron reduces the acetylcholine and serotonin induced gastrointestinal motility. Our study has indicated that ondansetron apart from having central action also has marked peripheral actions that play an important role in CINV and may act as a partial agonist. PMID- 26826827 TI - Enhancement of sodium taurocholate to the absorption of cefquinome. AB - The objective of the research was to detect the enhancement effect of sodium taurocholate on the absorption of cefquinome both in Caco-2 cells and rats. The absorption efficiency of cefquinome was determined by high performance liquid chromatography and calculated with apparent permeability coefficients (Papp) after Caco-2 cell monolayers treated odium taurocholate(2 mmol/L) and cefquinome. The results showed that the absorption of cefquinome in Caco-2 cell monolayers was significantly increased with the sodium taurocholate (2mmol/L). Similar results were also detected in the rats orally administrated with 1 mL PBS of cefquinome (20mg/mL) containing different concentration of sodium taurocholate (5 mmol/L, 10mmol/L and 20mmol/L) respectively. Compared with control group, sodium taurocholate at 10 and 20 mmol/L increased the absorption of cefquinome in rats from 0.26+/-0.04MUg/mL to 0.57+/-0.03MUg/mL, 0.78 +/-0.07MUg/mL respectively. These results indicated that sodium taurocholate could increase the intestinal permeability in a concentration-dependent mode, which will be useful for clinical treatment. PMID- 26826828 TI - In vitro antimicrobial activities of different solvent extracted samples from Iris germinica. AB - Antibacterial and antifungal activities of different solvents extracted samples of Iris germinica were carried out through disc diffusion assay. For this purpose five different solvent extracts were prepared with two concentrations (1 and 2 mg disc(-1)) and their antimicrobial activity was tested using disc diffusion assay against eight pathogenic bacteria viz. Staphylococcus aureus, B. subtilis, Bacillus atrophaeus, Escherichia coli, Pseudomonas aeruginosa, Erwinia carotovara, Klebsiella pneumoniae, Salmonella typhi and one fungal specie (Candida albicans). Butanol and ethyl acetate fraction were more effective to control the growth of different pathogens followed by chloroform, hexane and aqueous fractions respectively. C. albicans, S. aureus E. carotovara, B. atrophaeus and E. coli were comparatively susceptible inhibited by all extracts of I. germinica compared with the rest of microbes. Maximum activity was shown by ethyl acetate extracted samples against B. atrophaeus followed by the same solvent against E. carotovara. Butanol extracted samples were effective against B. subtilis showing 62% reduction in growth at 1 or 2mg disc(-1) concentration. From these results it can be concluded that different solvent extracted samples from the leaves of I. germinica possess varying degree of antimicrobial against different micro-organisms and can be a good sources of antibiotics for the treatment of certain bacterial and fungal diseases. PMID- 26826829 TI - Alternative treatment for iron deficiency anemia: Irocbin versus Sherbat Faulad. AB - The wide spread reason of anemia is Iron deficiency in Pakistan and even worldwide. A clinical trial was undertaken to assess the efficacy of Irocbin formulation for the treatment of iron deficiency anemia as compared to Sherbat Faulad. The curative evaluations of these medicines were recorded in clinically and biochemically identified cases of iron deficiency anemia. The therapeutic evaluation of the different drugs both test and control drug were conducted on the bases of improvement in the subjective signs and symptoms, clinical observations and biochemical investigations at periodic intervals during the course of therapy. This data was collected in the period November 2010 to November 2012 and completed the clinical trials. According to the statistical analysis comparison of data recorded by patients concerning to different variables, showed significant results between test and control groups (p<0.05). By applying ANOVA test, the p values for multiple comparisons of the levels of improvement of Hemoglobin after treatment exhibited significant difference as compared Sherbat Faulad and Irocbin. The control drug Sherbat Faulad with only iron component improves Hemoglobin level and the sign and symptoms but associated with side adverse effects. PMID- 26826830 TI - Antioxidant studies on monosubstituted chalcone derivatives - understanding substituent effects. AB - An over production of reactive oxygen species beyond basal levels generated continuously in the body as part of natural metabolic processes often results in serious and diverse disease conditions including cancer. Chalcones are known to possess good antioxidant properties, and structure activity relationship studies have been effective in designing molecules with better antioxidant profiles. The present study constitutes a preliminary investigation in seeking safer anti inflammatory agents with good antioxidant properties. A ten-membered chalcone library - comprising nine monosubstituted derivatives and the unsubstituted parent chalcone - characterized by varying stereoelectronic properties was screened for antioxidant activity using four well established in vitro assays including the hydrogen peroxide, nitric oxide and super oxide radical scavenging assays along with reducing power assay. The trends observed were then correlated with their anti-inflammatory profiles. All the derivatives except 4' phenylchalcone (4i) showed improved antioxidant profiles compared to the unsubstituted parent compound. The three bromo derivatives (4d, 4g and 4j) clearly portrayed the effect that bulky substituents may have on antioxidant activity; with the paraderivative 4j exhibiting the highest activity amongst these regioisomers. The 2'-hydroxy analog 4b is an optimized lead with the best antioxidant as well as anti-inflammatory properties. There exists a significant correlation between the antioxidant and anti-inflammatory activity. PMID- 26826831 TI - A Comparative biochemical study on two marine endophytes, Bacterium SRCnm and Bacillus sp. JS, Isolated from red sea algae. AB - Two marine endophytic bacteria were isolated from the Red Sea algae; a red alga; Acanthophora dendroides and the brown alga Sargassum sabrepandum. The isolates were identified based on their 16SrRNA sequences as Bacterium SRCnm and Bacillus sp. JS. The objective of this study was to investigate the potential anti microbial and antioxidant activities of the extracts of the isolated bacteria grown in different nutrient conditions. Compared to amoxicillin (25MUg/disk) and erythromycin (15MUg/disk), the extracts of Bacterium SRCn min media II, III, IV and V were potent inhibitors of the gram-positive bacterium Sarcina maxima even at low concentrations. Also, the multidrug resistant Staphylococcus aureus(MRSA) was more sensitive to the metabolites produced in medium (II) of the same endophyte than erythromycin (15MUg/disk). A moderate activity of the Bacillus sp. JS extracts of media I and II was obtained against the same pathogen. The total compounds (500ug/ml) of both isolated endophytes showed moderate antioxidant activities (48.9% and 46.1%, respectively). LC/MS analysis of the bacterial extracts was carried out to investigate the likely natural products produced. Cyclo(D-cis-Hyp-L-Leu), dihydrosphingosine and 2-Amino-1,3-hexadecanediol were identified in the fermentation medium of Bacterium SRCnm, whereas cyclo (D-Pro-L Tyr) and cyclo (L-Leu-L-Pro) were the suggested compounds of Bacillus sp. JS. PMID- 26826832 TI - Dose-dependent Medicinal Effects of Thymus haussknechtii Velen Grown Wild in Turkey. AB - In this study, it was aimed to determine dose-dependent interactions between phenolic contents and antioxidant, antibacterial and antifungal effect mechanisms of the infusions of Thymus haussknechtii Velen, naturally grown in the Eastern Anatolia region of Turkey. Therefore, the infusions of Thymus haussknechtii were tested and the interactions between phenolic contents and antioxidant, antibacterial and antifungal effect mechanisms were determined by way of different antioxidant, antibacterial and antioxidant test systems. The concentrations of Thymus haussknechtii showed strong hydrogen peroxide scavenging activity and free radical scavenging activity [1,1-diphenyl-2-picryl-hydrazil (DPPH) % inhibition]. Also, it was seen that Thymus haussknechtii infusions possessed strong antibacterial and antifungal activity against different gram negative and positive bacteria and fungi. In this study, positive correlations between antioxidant, antibacterial, antifungal potency and the total phenolic content of Thymus haussknechtii were found. When the concentration differences were examined, it was seen that concentrations of 4% had the most strong antioxidant, antibacterial and antifungal activity. As a result, Thymus haussknechtii can be reliable antioxidant, antibacterial antifungal substance at concentrations of 4% when it is used as a supplement to therapeutic regimens and for medicinal purposes. PMID- 26826833 TI - Efficacy of combination herbal product (Curcuma longa and Eugenia jambolana) used for diabetes mellitus. AB - The purpose of this research was to evaluate the efficacy of a combination herbal product that is traditionally used for managing diabetes mellitus. Herbal drug contains Curcuma longa and Eugenia jambolanain the ratio of 1:1. It was orally administered at the dose of 1082 mg/70 kg twice a day for a period of 6 weeks to alloxan induced diabetic rats and compared with glibenclamide (standard). The effects of drug were observed at intervals, with respect to random and fasting glucose levels. HbA1C was also monitored after the drug treatment to monitor the overall diabetic effect. Results revealed that the combination of two herbs significantly reduced fasting and random glucose levels with HbA1C of less than 6% (p<0.001) in comparison to diabetic control. The control of fasting blood glucose levels by herbal combination is similar to the standard drug, glibenclamide (p<0.05). Random glucose levels by herbal combination is better than standard drug after one week and six weeks of treatment (p<0.01 and p<0.001 respectively) and similar after third week of treatment (p<0.05). Also, herbal drug combination showed HbA1C closer to the standard drug. It shows that this herbal combination can be of potential benefit in managing diabetes mellitus in future. PMID- 26826834 TI - Development and bioevaluation of 99mTc(CO)3-labeled (1-azido-1-deoxy-beta-D glucopyranoside) complex as a potential tumor-seeking agent. AB - The 1,2,3-triazole-containing (1-azido-1-deoxy-beta-D-glucopyranoside) complex was synthesized using click chemistry approach and evaluated its potential as a tumor-seeking agent. In the present study, (99m)Tc-tricarbonyl labeled (1-azido-1 deoxy-beta-D-glucopyranoside) radiotracer [(99m)Tc(CO)(3)-BM], (where BM stands for biomolecule, e.g., (1-azido-1-deoxy-beta-D- glucopyranoside)) was synthesized via click chemistry approach and then labeled with technetium-99m through isolink kit. Radio labeled drug was tested for radiochemical purity and in vitro stability by chromatographic techniques. Normal distribution and tumoral uptake were studied in Swiss Webster mice. Radiochemical purity results show 97.9 +/ 1.5% labeling and its in vitro stability were studied at room temperature up to 5h. The radio labeled drug exhibited 73.6+/-1.1% binding with blood proteins. Normal distribution of drug shows prominent uptake in brain while in case of tumor-bearing mice, the uptake was maximum in tumor tissue and negligible amount was shown in brain. The biodistribution was further compared with 2-fluoro-2 deoxy glucose ((18)F-FDG), which was used as a positive control. The data indicate that (99m)Tc-tricarbonyl labeled (1-azido-1-deoxy-beta-D- glucopyranoside) radiotracer might be a feasible candidate with reasonable potential for tumor diagnosis. PMID- 26826835 TI - Report: Demographic profiles and sleep quality among patients on methadone maintenance therapy (MMT) in Malaysia. AB - Poor sleep quality was frequently reported by opioid dependence patients during methadone maintenance therapy (MMT). The study investigated a sample of patients on MMT to investigate the severity and prevalence of sleep problems in MMT patients. We evaluated sleep quality and disturbances of 119 Malay male patients from MMT clinics in Kelantan, Malaysia between March and July 2013 using the Pittsburgh Sleep Quality Index (PSQI)-Malay version. Patients' demographic, clinical data, past drug history and methadone treatment variables were recorded. Patients averaged 37.5 years of age (SD 6.79) and their mean age of first time illicit drug use was 19.3 years (SD 4.48). Their mean age of entering MMT was 34.7 years (SD 6.92) and the mean duration in MMT was 2.8 years (SD 2.13). The mean current daily dosage of methadone was 77.8 mg (SD 39.47) and ranged from 20 to 360 mg. The mean global PSQI score was 5.6 (SD 2.79) and 43.7% patients were identified as 'poor sleepers' (global PSQI scores >5). This study confirms the poor overall sleep quality among patients on MMT. The prevalence and severity of sleep problems in MMT patients should not be underestimated. PMID- 26826836 TI - Report: Sensitivity pattern of ceftriaxone against different clinical isolates. AB - Emerging resistance against broad-spectrum antibiotics for standard empiric therapy is a global concern. Ceftriaxone (broad spectrum, third generation cephalosporin) is widely used in tertiary care settings to treat severe bacterial infections usually non-responsive to other antibiotics. The aim of the study is to evaluate the current sensitivity pattern of ceftriaxone (30MUg/disk) among different clinical isolates. For this purpose, three hundred clinical isolates including Escherichia coli (25%), Staphylococcus aureus (30%), Salmonella typhi (17%) and Klebsiella pneumoniae(20%) were collected from different pathological laboratories of Karachi, Pakistan. The in-vitro sensitivity of different Gram positive and Gram-negative bacteria was determined by disk-diffusion technique using 0.5 McFarland standard. Results showed that ceftriaxone was highly sensitive against Escherichia coli (90%) and least sensitive against Klebsiella pneumoniae (65%). It is concluded that the sensitivity of ceftriaxone is progressively decreasing in comparison with past studies creating an alarming situation. Therefore, continuous surveillance is required to determine the current resistance status of clinical pathogens and for effective anti-microbial therapy. PMID- 26826837 TI - Synthesis and antibacterial screening of S-substituted derivatives of 5-(3,4 methylenedioxyphenyl)-1,3,4-oxadiazol-2-thiol. AB - The most emerging class among the heterocyclic compounds is 1,3,4-oxadiazoles for their diverse biological activities. In the present research work, piperonylic acid (1) was converted consecutively into corresponding ester (2), hydrazide (3) and 1,3,4-oxadiazole (4) through intermolecular cyclization. The synthesized compound 4 was subjected further to S-alkylation/aralkylation, using alkyl/aralkyl halides (5a-m) and S-substituted-1,3,4-oxadiazole derivatives were synthesized (6a-m). The structure elucidation of the synthesized molecules was processed through (1)H-NMR, IR and mass spectral data. The antibacterial activity showed these molecules moderately good inhibitors of gram-negative and gram positive bacteria. PMID- 26826838 TI - Antimicrobial profile of some novel keto esters: Synthesis, crystal structures and structure-activity relationship studies. AB - Rapid increase in bacterial resistance has become a major public concern by escalating alongside a lack of development of new anti-infective drugs. Novel remedies in the battle against multidrug-resistant bacterial strains are urgently needed. So, in this context, the present work is towards the investigation of antimicrobial efficacy of some novel keto ester derivatives, which are prepared by the condensation of substituted benzoic acids with various substituted phenacyl bromides in dimethylformamide at room temperature using triethylamine as a catalyst. The structural build-up of the target compounds was accomplished by spectroscopic techniques including FTIR, (1)H and (13)C NMR spectroscopy and mass spectrometry. The purity of the synthesized compounds was ascertained by elemental analysis. The molecular structures of compounds (4b) and (4l) were established by X-ray crystallographic analysis. The prepared analogues were evaluated for their antimicrobial activity against Gram-positive (Staphylococcus aureus, Micrococcus leuteus) and Gram-negative (Pseudomonas picketti, Salmonella setuball) bacteria and two fungal pathogenic strains (Aspergillus niger, Aspergillus flavus), respectively. Among the screened derivatives, several compounds were found to possess significant activity but (4b) and (4l) turned out to be lead molecules with remarkable antimicrobial efficacy. The structure activity relationship analysis of this study also revealed that structural modifications on the basic skeleton affected the antimicrobial activity of the synthesized compounds. PMID- 26826839 TI - Role of the antidiabetic drugs: Glibenclamide and metformin on the contractility of isolated rat uteri. AB - The current investigation has designed to study the role of two antidiabetics, glibenclamide and metformin on the spontaneous uterine contractions in the non diabetic non-pregnant female rats. The rat uteri were isolated and allocated to two groups: 1)the glibenclamide group: After recording the normal spontaneous uterine contractions, the vehicle (ethanol) and glibenclamide molar concentrations (10(-7), 10(-6) and 10(-5) M) were analyzed on uterine contractions by recording on smoked paper on a rotating kymograph drum, and 2) the metformin group: After recording the normal spontaneous uterine contractions, the metformin concentrations (10(-7), 10(-6) and 10(-5) M) were analyzed on uterine contractions. Responses to the two drugs and vehicle control (ethanol) were recorded for 30 min. Glibenclamide has not significantly effected on the amplitude and frequency of spontaneous contractions of the isolated rat uteri. Metformin also has no significant effect on the amplitude and frequency of spontaneous contractions of the isolated rat uteri. In conclusion, the two oral antidiabetics glibenclamide and metformin have not changed both the amplitude and frequency of spontaneous uterine contractions in the non-pregnant non-diabetic female rats. PMID- 26826840 TI - Analysis of genetics and chemical contents relation compared to commonly used Cissus quadrangularis L. and barcode markers of some Thailand Cissus species. AB - Several Cissus species are commonly used as traditional and modified medicines, and their chemical constituents are major point for precise usage. However, C. quadrangularis is the only species for which the usages and the chemical composition have been reported. These data should be investigated for other species in the genus. Eight species namely C. assamica, C. carnosa, C. elongata, C. hastata, C. javana, C. pteroclada, C. quadrangular is and C. repens were evaluated for genetic relationships and chemical composition. Constructed dendrogram shows high-powered efficiency of inter-simple sequence repeat (ISSR) data used which can clearly identify different and identical species. Genetic similarity (S) value of the identical species is 0.86, whereas for different species the value can vary from 0.53 to 0.75. Four highly related species (S=0.64 0.72), C. assamica, C. carnosa, C. hastata and C. repens were selected to undergo chemical study by gas chromatography-mass spectrometry (GC-MS) on the methanol crude extract. Only one compound, beta-sitosterol, found in the four species is identical to the compound reported from C. quadrangular is, where there were five identical chemicals found in the selected species. Species-specific barcode with rbcL region was constructed. Nucleotide variation was evaluated indicating genetic distance value of 0.025 to 0.072. PMID- 26826841 TI - Analgesic activity of alkyl piperidine derivatives. AB - Piperidine is the most significant scaffold which reveals therapeutic potential because of its conformationally flexible nature. During the course of present investigations synthetic quaternary salts of alkyl piperidine with various phenacyl bromides were explored for their possible analgesic activity. Compounds I analogs (1a-1f) and compound II analogs (IIa-IIf) showed varying degree of analgesic activity when compared with pethidine as standard and its duration by tail immersion method. PMID- 26826842 TI - Palm oil and ground nut oil supplementation effects on blood glucose and antioxidant status in alloxan-induced diabetic rats. AB - This study investigated the effects of two common cooking oils (palm oil, PO) and (groundnut oil, GO) supplementation on the antioxidant status and diabetic indices in Alloxan (100mg/kg) induced diabetic Wistar rats. A total of forty eight Wistar rats of both sexes were used for this study. They were divided into four groups of 12 animals each as: control, diabetic non-supplemented, diabetic supplemented with PO (200mg/kg/day) and diabetic supplemented with GO (200mg/kg/day) rats. Blood glucose, plasma vitamin E, SOD, Total Protein and Albumin levels were measured using standard laboratory procedures. After three weeks of supplementation there was a significant (p<0.05) reduction in blood glucose of supplemented groups compared with the diabetic non-supplemented group. Plasma Vitamins C and E, SOD, and Albumin levels were significantly (p<0.05) increased in the supplemented groups when compared with the diabetic non supplemented group. However, the plasma levels of these parameters were found to be significantly (p<0.05) higher in the GO supplemented rats compared with the PO supplemented group. The plasma vitamin C levels in the diabetic groups were lower than in other groups while increased levels in the plasma total protein were not significant. There was no significant difference in the measured parameters in reference to the gender of the animals. It was concluded from this study that GO exhibited superior antioxidant activities and that the supplementation of red palm oil and ground nut oil as a source of antioxidant was beneficial in diabetic state as it reduced blood glucose and enhance antioxidant status. PMID- 26826843 TI - Antioxidant study of flavonoid derivatives from the aerial parts of Rhus natalensis growing in Saudi Arabia. AB - Phytochemical study of the CH(2)Cl(2) soluble fraction of the aerial parts of R. natalensis resulted in the isolation and identification of six flavonoid derivatives, beta-amyrin and beta-sitosterol glucoside (daucosterol). The isolated compounds were identified utilizing physical, chemical and different spectral methods including UV, 1D- 2D-NMR and MS. The compounds were identified as four flavanones; 7-O-methyl hesperetin (1), 7-O-methyl naringenin (4), (-) homoeriodictyol (eriodictyonone) (5), eriodictyol-7-methyl ether (6) and two flavones; 7-O-methyl isokaemferide (2) and genkwanin (3). The isolated compounds as well as some available standards representing structurally similar flavones and flavanones were used to study their antioxidant potential using DPPH and try to explore the impact of structures on the antioxidant activity. In other assays flavanones were less active than flavones as antioxidant due to lack of the C-4 carbonyl group in conjugation with 2,3-double bond. However, in DPPH assay based on the ability of molecules to donate hydrogen flavanones were found more active than flavones. PMID- 26826844 TI - Swine hind limb model for supermicrosurgical lymphaticovenular anastomosis training. PMID- 26826845 TI - Comparison of drugs used by nightclub patrons and criminal offenders in Oslo, Norway. AB - The aim of this study was to investigate psychoactive drug use among nightclub patrons by analysing samples of oral fluid and compare with findings in blood samples from criminal suspects. We hypothesized that the profile of illicit drug use among nightclub patrons is different from what we observe in those forensic cases. Research stations were established outside nine popular nightclubs with different profiles and patron-characteristics in downtown Oslo. Data and sample collection was conducted on Fridays and Saturdays in March and May 2014. Individuals and groups who entered defined recruitment zones from 23:00 to 03:30 were invited to participate in this voluntary and anonymous study. Oral fluid was collected using the Intercept Oral Fluid Sampling Device. Methanol was added to increase the recovery of cannabinoids from the device. Sample preparation was performed using liquid-liquid extraction with ethyl acetate/heptane (4:1) after adding internal standards, ammonium carbonate buffer pH 9.3 and Triton X100. The first 80 samples were analysed for 122 substances, which included psychoactive medicinal drugs, classical illicit drugs and new psychoactive substances (NPS). Based on the findings and discussions with police and customs authorities, the remaining oral fluid samples were analysed for 46 substances. Among the 500 samples collected during the study period, we found illicit drugs in 25.4% and medicinal drugs in 4.2% of the samples. The most prevalent substances were: cocaine 14.6%, THC 12.4%, amphetamine/methamphetamine 2.8%, diazepam 1.2% and clonazepam 1.0%. Various NPS were found in 1.4% of the samples. The prevalence of drugs in blood samples from criminal suspects were for cocaine 3.4%, THC 34.7%, amphetamine/methamphetamine 37.0%, diazepam 12.0%, and clonazepam 29.3%. Multi drug use was more common among criminal suspects (41.3%) than among club patrons (6.8%). The results showed that the drug use pattern among nightclub patrons was substantially different from the drug use pattern manifested by individuals apprehended by the police suspected for criminal conduct. PMID- 26826846 TI - Behavioural and pharmacological characterization of a novel cannabinomimetic adamantane-derived indole, APICA, and considerations on the possible misuse as a psychotropic spice abuse, in C57bl/6J mice. AB - The novel adamantane derivative APICA (N-(adamantan-1-yl)-1-pentyl-1H-indole-3 carboxamide) was recently identified as a cannabinomimetic indole of abuse. Despite its novel structure, APICA recalls cannabinomimetic indoles, such as representative member JWH-018. In present study, the effects of APICA (1-3mg/kg, i.p.) were tested in C57BL/6J mice, in the Tetrad task which includes the assessment of: body temperature; locomotor activity and behavioural reactivity; nociception; motor coordination; declarative memory. Furthermore, pre-treatment with the CB1 antagonist AM251 (3mg/kg, i.p.) or the CB2 antagonist AM630 (3mg/kg, i.p.) was carried out to characterize APICA activity. Our results show that APICA was able to dose-dependently decrease locomotor activity and behavioural reactivity in the open field, whereas only the highest dose was able to induce hypothermia, analgesia, motor incoordination and recognition memory impairment, with respect to vehicle (p<0.01; p<0.001). The pretreatment with the CB1 antagonist AM251 elicited an increase in body temperature, total distance travelled in the open field, latency to fall down in the Rotarod, and a decrease in tail flick latency (p<0.05; p<0.01). On the other hand, pretreatment with AM630 did not induced significant differences on APICA effects. This study supports preliminary reports on APICA cannabinomimetic properties, extending its detrimental effects on cognitive function. Moreover, these properties can be attributed to the CB1 receptor activity, indicating APICA as a selective CB1 receptor agonist. PMID- 26826847 TI - Influence of thermal hair straightening on cannabis and cocaine content in hair. AB - It has been shown that cosmetic treatment like bleaching and perming may lead to an important decrease of drugs of abuse content in hair. Currently, hair straightening has become a regular hair treatment especially for women. The aim of this preliminary study was to investigate the effect of in vitro treatment of hair with heat straightener on cannabis and cocaine concentrations in hair. 17 positive cannabis and 7 positive cocaine hair samples were treated in vitro with a hair straightener. During this treatment hair was put sequentially 30 times in contact with heated iron plates at 200 degrees C during 2s corresponding to a total time of contact of 1min. THC and Cannabinol (CBN) were analysed in cannabis positive hair and cocaine, benzoylecgonin (BZE) and cocaethylene were analysed in cocaine positive hair. Analyses were performed with routine methods using GC/MS in electron impact mode. Regarding cannabis results a decrease of THC concentrations was found in 11 of 17 hair samples after thermal treatment, whereas in 6 cases an increase was shown. In all the hair samples CBN concentrations was explicitly higher after the in vitro treatment. Regarding cocaine results cocaine and cocaethylene concentrations decreased after treatment in all seven hair samples; in contrast, higher concentrations of BZE were determined. The strong increase of CBN and BZE content in hair after thermal treatments may be due to the fact that THC is converted by heat into CBN and cocaine into BZE, thus changing the respective ratios of the analysed substances. In conclusion, thermal straightening should be considered as other cosmetic hair treatments for a correct interpretation of hair results. PMID- 26826849 TI - Development of a method for the determination of cocaine, cocaethylene and norcocaine in human breast milk using liquid phase microextraction and gas chromatography-mass spectrometry. AB - Most licit and illicit substances consumed by the nursing mother might be excreted in breast milk, which may cause potential short and long term harmful effects for the breastfed infant. The extraction of substances from this matrix represents an analytical challenge due to its high protein and fat content as well as the fact that its composition changes during postpartum period. The aim of the present study was to develop a liquid phase microextraction (LPME) method for detection of the active substances: cocaine (COC), cocaethylene (CE) and norcocaine (NCOC) in human breast milk using gas chromatography-mass spectrometry (GC-MS). Validation was performed working on spiked human breast milk samples. The limits of detection (LOD) and quantification (LOQ) were of 6 and 12ng/mL, respectively, for all analytes. Calibration curves were linear over a concentration range of 12.0ng/mL-1000ng/mL (r(2)=0.99). No interferences were noticed at the retention times of interest. Within-run and between-run precision was always less or equal to 15 as % relative standard deviation, and bias ranged from 3 to 18%. Forty six milk samples were analyzed. Only one sample was confirmed to be COC positive (138ng/mL) and another one presented COC concentration near the LOD (6ng/mL). This method has shown to be a reliable alternative for the determination of cocaine, cocaethylene and norcocaine in human breast milk in the fields of clinical and forensic toxicology. LPME extraction procedure demonstrated to be a rather promising, low cost and environmental-friendly technique for the purpose of this study. PMID- 26826848 TI - The involvement of prescribed drugs in road trauma. AB - Coroners files and toxicological records of fatally-injured drivers in Victoria from 2000 to 2006 and from 2007 to 2013 were reviewed in separate studies to establish the role of prescribed drugs on crash risk. 2638 driver fatalities were included in the study, which represented over 97% of all driver fatalities in this period. The detection limits of the drugs were at the low end of those seen with common illicit drugs or prescribed drugs. Drugs of any type were found in 34.4% of the study group, medicinal drugs 21.2%, and alcohol (>=0.05 gram/100mL) was found in 24.8%. The prevalence of the most common drugs detected that are legally available by prescription were anti-depressants (7.9%), benzodiazepines (7.0%), opiates/opioids (6.6%), and sedating anti-histamines (1.1%). Each driver was assessed for responsibility using a previously published and validated method. The crash risk of drivers taking opioids, benzodiazepines, or anti depressants (primarily the serotonin reuptake inhibitors), were not significantly over-represented compared to the drug-free control group, although there was a suggestion of increased crash risk for benzodiazepines. Crash risk was elevated for drivers using cannabis (by presence of THC in blood at>2ng/mL) and amphetamines. These data show that drivers using medicinal drugs alone are unlikely to show significant crash risk even if drugs are potentially impairing. PMID- 26826850 TI - The cholesterol levels in median nerve and post-mortem interval evaluation. AB - Cholesterol levels in the median nerve were studied at various post-mortem intervals (PMIs). Single median nerve samples were collected from the wrists of 36 subjects during forensic autopsies of subjects with known circumstances and times of death. Although the absolute values varied, increments in cholesterol concentration were recorded. Subsequently, 16 subjects who did not suffer of any neurological and/or metabolic diseases with known times and circumstances of death were enrolled. For each enrolled subject, two samples were collected from the wrist at an interval of approximately two hours (t1 and t2). The obtained results revealed a gradual increase in cholesterol level with increasing time since death. The cholesterol concentration data obtained for each subject at t1 and t2 were correlated with the time since death, a linear interpolation was applied, and the PMI was back-calculated. Similar trends were obtained for the samples collected at similar PMIs; thus, three groups were considered: PMI<48h, 4878h. Good correlation coefficients were obtained, especially for the first group (R(2)=0.9362) for which the PMI could be calculated with an error that ranged from -4 to 5.9h. Although it requires further confirmation via analyses of larger numbers of samples, the method proposed here can currently be applied to PMI determinations. PMID- 26826851 TI - Responses of peat carbon at different depths to simulated warming and oxidizing. AB - Warming and water table drawdown greatly reshape peatland carbon cycle, especially when considering the old carbon stored under the peatland subsurface. However, little is known about the effects of warming, oxidizing by drying or their combination on carbon decomposition at different depths (0-100 cm) of peat. In this research, soil of different depths from Zoige Plateau was incubated in four scenarios (8 degrees C-anaerobic, 8 degrees C-aerobic, 18 degrees C anaerobic and 18 degrees C-aerobic) to detect the exported carbon. Our result showed that soil respiration (Rs) increased obviously with enhanced temperature and oxygen. The total CO2 fluxes of 2400.22 +/- 57.69 mg m(-2) d(-1) under 8 degrees C-anaerobic condition increased by 73.6%, 40.7% and 176.5% with warming, oxidizing and their combined effect, respectively. The average dissolved organic carbon (DOC) concentration was 74.90 +/- 8.09 mg kg(-1) under 8 degrees C anaerobic condition, but increased by 53.5%, 44% and 159.4%, respectively under the condition of warming, oxidizing and their combination. Rs and its variation under warming and oxidization differed significantly among different depths, probably caused by the differences of soil substrate, especially the variation in distribution of soil microbes and enzymes among depths of peatlands. By classifying the source of Rs as young soil (YS: 0-20 cm) and old soil (OS: 21-100 cm), this reseaerch found that OS accounted for a huge part of total Rs under 8 degrees C-anaerobic condition (CO2: 74.2%; DOC: 60.7%). Such relative contribution of OS to total Rs did not change obviously with warming or oxidizing. Though YS and OS responded equally to warming and oxidizing, OS was responsible for a larger proportion of total increase in Rs. Compared with other studies, we concluded that peatlands soil in our field of mid-latitude and high altitude is less sensitive to warming and oxidizing than peatlands of higher latitude, but that OS of this peatlands is more critical in predicting regional carbon cycle. PMID- 26826852 TI - Estimating dermal transfer of copper particles from the surfaces of pressure treated lumber and implications for exposure. AB - Lumber pressure-treated with micronized copper was examined for the release of copper and copper micro/nanoparticles using a surface wipe method to simulate dermal transfer. In 2003, the wood industry began replacing CCA treated lumber products for residential use with copper based formulations. Micronized copper (nano to micron sized particles) has become the preferred treatment formulation. There is a lack of information on the release of copper, the fate of the particles during dermal contact, and the copper exposure level to children from hand-to-mouth transfer. For the current study, three treated lumber products, two micronized copper and one ionic copper, were purchased from commercial retailers. The boards were left to weather outdoors for approximately 1year. Over the year time period, hand wipe samples were collected periodically to determine copper transfer from the wood surfaces. The two micronized formulations and the ionic formulation released similar levels of total copper. The amount of copper released was high initially, but decreased to a constant level (~1.5mgm(-2)) after the first month of outdoor exposure. Copper particles were identified on the sampling cloths during the first two months of the experiment, after which the levels of copper were insufficient to collect interpretable data. After 1month, the particles exhibited minimal changes in shape and size. At the end of 2-months, significant deterioration of the particles was evident. Based on the wipe sample data, a playground visit may result in a potential exposure to 2.58mg of copper, which is near or exceeds the daily tolerable upper intake limits for children under the age of 8, if completely ingested through hand-to-mouth transfer. While nanoparticles were found, there is not enough information to estimate the exposure from the released particles due to a lack of published literature on copper carbonate. PMID- 26826853 TI - Transient and periodic spatiotemporal structures in a reaction-diffusion mechanics system. AB - We study transient spatiotemporal structures induced by a weak space-time localized stimulus in an excitable contractile fiber within a two-component globally coupled reaction-diffusion model. The model which we develop allows us to analyze various regimes of excitation spreading and determine origin of the induced structures for various contraction types (defined by the fiber fixation) and global coupling strengths. One of the most notable effects we observed is the after-excitation effect. It leads to emergence of multiple excitation pulses excited by a single external stimulus and can result in long-lasting transient activity and appearance of new oscillatory attractor regimes, including the ones with multiple phase clusters. PMID- 26826854 TI - Dynamic range in the C. elegans brain network. AB - We study external electrical perturbations and their responses in the brain dynamic network of the Caenorhabditis elegans soil worm, given by the connectome of its large somatic nervous system. Our analysis is inspired by a realistic experiment where one stimulates externally specific parts of the brain and studies the persistent neural activity triggered in other cortical regions. In this work, we perturb groups of neurons that form communities, identified by the walktrap community detection method, by trains of stereotypical electrical Poissonian impulses and study the propagation of neural activity to other communities by measuring the corresponding dynamic ranges and Steven law exponents. We show that when one perturbs specific communities, keeping the rest unperturbed, the external stimulations are able to propagate to some of them but not to all. There are also perturbations that do not trigger any response. We found that this depends on the initially perturbed community. Finally, we relate our findings for the former cases with low neural synchronization, self criticality, and large information flow capacity, and interpret them as the ability of the brain network to respond to external perturbations when it works at criticality and its information flow capacity becomes maximal. PMID- 26826855 TI - Lagrangian statistics in weakly forced two-dimensional turbulence. AB - Measurements of Lagrangian single-point and multiple-point statistics in a quasi two-dimensional stratified layer system are reported. The system consists of a layer of salt water over an immiscible layer of Fluorinert and is forced electromagnetically so that mean-squared vorticity is injected at a well-defined spatial scale ri. Simultaneous cascades develop in which enstrophy flows predominately to small scales whereas energy cascades, on average, to larger scales. Lagrangian correlations and one- and two-point displacements are measured for random initial conditions and for initial positions within topological centers and saddles. Some of the behavior of these quantities can be understood in terms of the trapping characteristics of long-lived centers, the slow motion near strong saddles, and the rapid fluctuations outside of either centers or saddles. We also present statistics of Lagrangian velocity fluctuations using energy spectra in frequency space and structure functions in real space. We compare with complementary Eulerian velocity statistics. We find that simultaneous inverse energy and enstrophy ranges present in spectra are not directly echoed in real-space moments of velocity difference. Nevertheless, the spectral ranges line up well with features of moment ratios, indicating that although the moments are not exhibiting unambiguous scaling, the behavior of the probability distribution functions is changing over short ranges of length scales. Implications for understanding weakly forced 2D turbulence with simultaneous inverse and direct cascades are discussed. PMID- 26826856 TI - Backbones in the parameter plane of the Henon map. AB - Parameter plane (b, a) of the real Henon map has been investigated for curves of bifurcation, curves of homoclinic heteroclinic onsets, and also searching for borders of areas variously characterized. Such curves are, in general, complicated and show singularities. Pieces of two monotone curves, spanning the (b, a) parameter plane of the real Henon map, can be detected in four quite different studies appeared along the years 1982-2008. We study the extent of their similarity to read and interpret them into the same curves. To us, these two curves are the accumulation loci of bifurcation curves of two principal families of periodic sinks of type "period-adding machine." We call them "backbones," because they are monotone; moreover, they are the borders of some important regions in the (b, a)-plane. Hamouly and Mira in 1982 [C. R. Acad. Sc. Paris1 293, 525-528 (1982)] studied the structure of bifurcation of periodic orbits and their mutual position and intersection. Gonchenko et al. [SIAM J. Appl. Dyn. Syst. 4, 407-436 (2005)] display the continuation (in parameter plane) of the first heteroclinic connection and of the first homoclinic connection between the two fixed points of the map. Alligood and Sauer [Commun. Math. Phys. 120, 105-119 (1988)] studied parameter regions characterized by the same rotation number of the "accessible" periodic saddle. Finally, Lorenz [Physica D 237, 1689 1704 (2008)] in 2008 draws areas in the parameter plane statistically characterized by a finite attractor. In this paper, we show how these criteria interact. We therefore conjecture that the wealth of curves of homoclinic onsets could be in general hierarchized by the structure of accessible saddles. PMID- 26826857 TI - The effect of randomness for dependency map on the robustness of interdependent lattices. AB - The percolation for interdependent networks with identical dependency map follows a second-order phase transition which is exactly the same with percolation on a single network, while percolation for random dependency follows a first-order phase transition. In real networks, the dependency relations between networks are neither identical nor completely random. Thus in this paper, we study the influence of randomness for dependency maps on the robustness of interdependent lattice networks. We introduce approximate entropy(ApEn) as the measure of randomness of the dependency maps. We find that there is critical ApEnc below which the percolation is continuous, but for larger ApEn, it is a first-order transition. With the increment of ApEn, the pc increases until ApEn reaching ApEnc (') and then remains almost constant. The time scale of the system shows rich properties as ApEn increases. Our results uncover that randomness is one of the important factors that lead to cascading failures of spatially interdependent networks. PMID- 26826858 TI - Local immunization strategy based on the scores of nodes. AB - The problem of finding a better immunization strategy for controlling the spreading of the epidemic with limited resources has attracted much attention because of its great theoretical significance and wide application. In this paper, we propose a successful immunization strategy only depending on local information. Our strategy initializes the scores of nodes with the values of their degree and recalculates the score of a certain immunized node based on its local information, and then replaces the certain immunized node with its nonimmunized higher-score neighbor. To test the effectiveness of the proposed strategy, we conduct the experiments on several synthetic networks and real-world networks. The results show that the proposed strategy outperforms the existing well-known local strategies, even the degree centrality targeted strategy. PMID- 26826859 TI - Reconstructing three-dimensional reentrant cardiac electrical wave dynamics using data assimilation. AB - For many years, reentrant scroll waves have been predicted and studied as an underlying mechanism for cardiac arrhythmias using numerical techniques, and high resolution mapping studies using fluorescence recordings from the surfaces of cardiac tissue preparations have confirmed the presence of visible spiral waves. However, assessing the three-dimensional dynamics of these reentrant waves using experimental techniques has been limited to verifying stable scroll-wave dynamics in relatively thin preparations. We propose a different approach to recovering the three-dimensional dynamics of reentrant waves in the heart. By applying techniques commonly used in weather forecasting, we combine dual-surface observations from a particular experiment with predictions from a numerical model to reconstruct the full three-dimensional time series of the experiment. Here, we use model-generated surrogate observations from a numerical experiment to evaluate the performance of the ensemble Kalman filter in reconstructing such time series for a discordant alternans state in one spatial dimension and for scroll waves in three dimensions. We show that our approach is able to recover time series of both observed and unobserved variables matching the truth. Where nearby observations are available, the error is reduced below the synthetic observation error, with a smaller reduction with increased distance from observations. Our findings demonstrate that state reconstruction for spatiotemporally complex cardiac electrical dynamics is possible and will lead naturally to applications using real experimental data. PMID- 26826860 TI - Classification of boundary equilibrium bifurcations in planar Filippov systems. AB - If a family of piecewise smooth systems depending on a real parameter is defined on two different regions of the plane separated by a switching surface, then a boundary equilibrium bifurcation occurs if a stationary point of one of the systems intersects the switching surface at a critical value of the parameter. We derive the leading order terms of a normal form for boundary equilibrium bifurcations of planar systems. This makes it straightforward to derive a complete classification of the bifurcations that can occur. We are thus able to confirm classic results of Filippov [Differential Equations with Discontinuous Right Hand Sides (Kluwer, Dordrecht, 1988)] using different and more transparent methods, and explain why the 'missing' cases of Hogan et al. [Piecewise Smooth Dynamical Systems: The Case of the Missing Boundary Equilibrium Bifurcations (University of Bristol, 2015)] are the only cases omitted in more recent work. PMID- 26826861 TI - Chaos synchronization in vertical-cavity surface-emitting laser based on rotated polarization-preserved optical feedback. AB - In this paper, the influence of the rotating polarization-preserved optical feedback on the chaos synchronization of a vertical-cavity surface-emitting laser (VCSEL) is investigated experimentally. Two VCSELs' polarization modes (XP) and (YP) are gradually rotated and re-injected back into the VCSEL. The anti-phase dynamics synchronization of the two polarization modes is evaluated using the cross-correlation function. For a fixed optical feedback, a clear relationship is found between the cross-correlation coefficient and the polarization angle thetap. It is shown that high-quality anti-phase polarization-resolved chaos synchronization is achieved at higher values of thetap. The maximum value of the cross-correlation coefficient achieved is -0.99 with a zero time delay over a wide range of thetap beyond 65 degrees with a poor synchronization dynamic at thetap less than 65 degrees . Furthermore, it is observed that the antiphase irregular oscillation of the XP and YP modes changes with thetap. VCSEL under the rotating polarization optical feedback can be a good candidate as a chaotic synchronization source for a secure communication system. PMID- 26826862 TI - Characterizing the signature of flame flashback precursor through recurrence analysis. AB - In this paper, it is shown that prior to flashback, small dynamical changes appear in the system. These changes appear as a drift in the recurrence plots and are found to be associated with a gradual increase in the determinism and recurrence rate. Thus, this study indicates that precursors to flame flashback exist and can be detected in the multidimensional phase space reconstructed from pressure measurements acquired during flashback. This observation could have broad academic as well as industrial implications. PMID- 26826863 TI - The pieces fit: Constituent structure and global coherence of visual narrative in RSVP. AB - Recent research has shown that comprehension of visual narrative relies on the ordering and timing of sequential images. Here we tested if rapidly presented 6 image long visual sequences could be understood as coherent narratives. Half of the sequences were correctly ordered and half had two of the four internal panels switched. Participants reported whether the sequence was correctly ordered and rated its coherence. Accuracy in detecting a switch increased when panels were presented for 1 s rather than 0.5 s. Doubling the duration of the first panel did not affect results. When two switched panels were further apart, order was discriminated more accurately and coherence ratings were low, revealing that a strong local adjacency effect influenced order and coherence judgments. Switched panels at constituent boundaries or within constituents were most disruptive to order discrimination, indicating that the preservation of constituent structure is critical to visual narrative grammar. PMID- 26826864 TI - Do humans spontaneously take the perspective of others? AB - A growing number of authors have argued that humans automatically compute the visual perspective of other individuals. Evidence for this has come from the dot perspective task in which observers are faster to judge the number of dots in a display when a human avatar has the same perspective as the observer compared to when their perspectives are different. The present experiment examined the 'spontaneous perspective taking' claim using a variant of the dot perspective paradigm in which we manipulated what the avatar could see via physical barriers that either allowed the targets to be seen by the avatar or occluded this view. We found a robust 'perspective taking' effect despite the avatar being unable to see the same stimuli as the participant. These findings do not support the notion that humans spontaneously take the perspective of others. PMID- 26826865 TI - Factors associated with postpartum depressive symptomatology in Brazil: The Birth in Brazil National Research Study, 2011/2012. AB - BACKGROUND: Depression is one of the most common postpartum mental disorders. Many sociodemographic and individuals risk factors are associated with maternal depression but the impact of high levels of birth intervention is unclear. The Brazilian context is characterized by excessive intervention and frequent non compliance with recommended obstetric protocols. This study therefore examined the impact of sociodemographic, individual, and obstetric risk factors in postpartum depression. METHODS: The Birth in Brazil research study is a national study of 23,894 postpartum women. Information about depression was obtained by telephone interview at 6-18 months after birth and was measured using the Edinburgh Postnatal Depression Scale. RESULTS: The prevalence of probable cases of depression was 26.3%. A multiple logistic regression model identified significant sociodemographic and individual risk factors as: brown skin color (OR=1.15 CI 1.01-1.31), lower economic class (OR=1.70 CI 1.41-2.06), alcohol use (OR=1.41 CI 1.09-1.84) and a history of mental disorders (OR=3.13 CI 1.80-5.44). Significant obstetric factors were unplanned pregnancy (OR=1.22 CI 1.05-1.43 for wanted later and OR=1.38 CI 1.20-1.60 for never wanted), multiparity (OR=1.97 CI 1.58-2.47 for 3 or more children), and poor care during birth (OR=2.02 CI 1.28 3.20) or of the newborn (OR=2.16 CI 1.51-3.10). Obstetric interventions and complications were not associated with maternal depression. LIMITATIONS: Depression was measured only once so we are not able to examine the course over time. The associational and reverse causality cannot be ruled out for some variables. CONCLUSIONS: The prevalence of postpartum depression is high in Brazilian women six months after birth. Poor care of women and babies during birth is more important in postpartum depression than physical obstetric or neonatal intervention and complications. PMID- 26826866 TI - A suicidal pregnant patient's request for premature Cesarean section: Clinical and ethical challenges. AB - We present the case of a 36-year-old lady with severe borderline personality disorder and depression, who made repeated requests for an immediate Cesarean section at 31 weeks of gestation. Her mood was extremely depressed and she had intense suicidal thoughts. She was worried that she would kill herself and the baby, therefore believing that early delivery would save the baby's life. This was a challenging case that required multidisciplinary collaboration, suicide risk assessment and detailed evaluation of mental capacity. The clinical and ethical dilemmas of this case are discussed by a team of psychiatrists, obstetricians and neonatologists. PMID- 26826867 TI - Plasma adiponectin and depressive symptoms during pregnancy and the postpartum period: A prospective cohort study. AB - BACKGROUND: Some authors have described an inverse association between adiponectin and depression, but this association has not yet been investigated during the perinatal period. OBJECTIVE: To evaluate the association between the plasma adiponectin levels and symptoms of depression in women from early pregnancy to 30-45 days postpartum. METHODS: A prospective cohort of 235 women was analyzed, with four waves of follow-up: 5-13th, 22-26th, and 30-36th gestational weeks and 30-45 days postpartum. Depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS; cutoff >= 11). The plasma adiponectin concentrations were measured using an enzyme-linked immunosorbent assay. The statistical analyses included linear mixed effects regressions to model the association between these time-dependent variables. RESULTS: The prevalence of depressive symptoms was 35.5%, 22.8%, 21.8%, and 16.9% and the median (ug/mL) adiponectin levels were 4.8, 4.7, 4.4, and 7.5 in the 1st, 2nd, and 3rd trimesters and the postpartum period, respectively. Women who remained non-depressed throughout the study tended to have higher values of adiponectin throughout pregnancy and the postpartum period compared to those who had depressive symptoms at least once, but this difference was not statistically significant (beta=-0.14; p=0.071). There was no statistically significant association between the plasma adiponectin levels and the EPDS scores in the multiple model (beta=-0.07; p=0.320). LIMITATIONS: Losses to follow-up, different procedures for the blood draws at the prenatal and postpartum visits, and the presence of a nested clinical trial with omega-3 supplementation. CONCLUSION: The plasma adiponectin levels were not associated with depressive symptoms during the perinatal period. PMID- 26826868 TI - Oncocytoma and noncompaction in metabolic myopathy. PMID- 26826869 TI - As good as it gets? Retention in care of people newly diagnosed with HIV at the Sydney Sexual Health Centre. AB - A retrospective review of all new HIV positive patients attending the Sydney Sexual Health Centre in 2012 and 2013 was performed to ascertain the retention in care rates, proportion that achieved viral suppression, number of SMS reminders sent and counselling uptake. Ninety-six patients had a retention rate of 66%. Thirty-three patients (34%) were not retained in care, 16 (17%) were knowingly attending another healthcare service with 17 (18%) categorised as lost to follow up. Counselling referrals had a 74% (71/96) uptake (95%CI: 5.08-69.69, P<0.001), with SMS reminders sent in 97% (93/96) of cases (95%CI: not possible with zero count cells, P=0.038). Overall, the clinic performed well compared with international standards but the lost to follow-up rate remains a concern. PMID- 26826870 TI - Dialysis with high-flux membranes significantly affects plasma levels of neutrophil gelatinase-associated lipocalin. PMID- 26826871 TI - Tuberculosis in early medieval Switzerland--osteological and molecular evidence. AB - Lesions consistent with skeletal tuberculosis were found in 13 individuals from an early medieval skeletal sample from Courroux (Switzerland). One case of Pott's disease as well as lytic lesions in vertebrae and joints, rib lesions and endocranial new bone formation were identified. Three individuals with lesions and one without were tested for the presence of Myobacterium tuberculosis complex (MTBC) ancient DNA (aDNA), and in two cases, evidence for MTBC aDNA was detected. Our results suggest the presence of tuberculosis in the analysed material, which is in accordance with other osteological and biomolecular research that reported a high prevalence of tuberculosis in medieval skeletons. PMID- 26826872 TI - [Continuing to make progress]. PMID- 26826873 TI - HOTAIR Promotes Proliferation, Migration, and Invasion of Ovarian Cancer SKOV3 Cells Through Regulating PIK3R3. AB - BACKGROUND: The aim of this study was to determine the effect on proliferation, migration, and invasion after silencing HOTAIR in ovarian cancer SKOV3 cells, and to elucidate the potential mechanism. MATERIAL/METHODS: We analyzed the mRNA expression level of HOTAIR and PIK3R3 in ovarian cancer SKOV3, OVCAR3, and A2780 cell lines. We analyzed the mRNA expression level of HOTAIR and PIK3R3 in ovarian SKOV3 after transection with miR-214 or miR-217. We analyzed the mRNA and protein expression level of PIK3R3 when silencing HOTAIR. We analyzed the expression of HOTAIR when silencing PIK3R3. We analyzed the proliferation, migration and invasion in ovarian cancer SKOV3 after silencing HOTAIR or PIK3R3. RESULTS: The expression of HOTAIR and PIK3R3 in ovarian SKOV3 and OVCAR3 was increased compared with A2780 cells (P<0.05). The mRNA level of HOTAIR and PIK3R3 in ovarian cancer SKOV3 cells was decreased when transected with miR-214 or miR-217 compared to negative control (p<0.05). The mRNA and protein level of PIK3R3 was decreased when HOTAIR was silenced and the mRNA level of HOTAIR was decreased when PIK3R3 was silenced (p<0.05). The proliferation, migration and invasion was decreased in ovarian SKOV3 when HOTAIR or PIK3R3 was silenced (p<0.05). CONCLUSIONS: HOTAIR can promote proliferation, migration, and invasion in ovarian SKOV3 cells as a competing endogenous RNA. PMID- 26826874 TI - Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression. AB - BACKGROUND: Neuroimaging studies of patients with major depression have revealed abnormal intrinsic functional connectivity measured during the resting state in multiple distributed networks. However, it is unclear whether these findings reflect the state of major depression or reflect trait neurobiological underpinnings of risk for major depression. METHODS: We compared resting-state functional connectivity, measured with functional magnetic resonance imaging, between unaffected children of parents who had documented histories of major depression (at-risk, n = 27; 8-14 years of age) and age-matched children of parents with no lifetime history of depression (control subjects, n = 16). RESULTS: At-risk children exhibited hyperconnectivity between the default mode network and subgenual anterior cingulate cortex/orbital frontal cortex, and the magnitude of connectivity positively correlated with individual symptom scores. At-risk children also exhibited 1) hypoconnectivity within the cognitive control network, which also lacked the typical anticorrelation with the default mode network; 2) hypoconnectivity between left dorsolateral prefrontal cortex and subgenual anterior cingulate cortex; and 3) hyperconnectivity between the right amygdala and right inferior frontal gyrus, a key region for top-down modulation of emotion. Classification between at-risk children and control subjects based on resting-state connectivity yielded high accuracy with high sensitivity and specificity that was superior to clinical rating scales. CONCLUSIONS: Children at familial risk for depression exhibited atypical functional connectivity in the default mode, cognitive control, and affective networks. Such task-independent functional brain measures of risk for depression in children could be used to promote early intervention to reduce the likelihood of developing depression. PMID- 26826875 TI - Posttraumatic Stress Disorder as a Catalyst for the Association Between Metabolic Syndrome and Reduced Cortical Thickness. AB - BACKGROUND: Metabolic syndrome (MetS), defined by a constellation of cardiometabolic pathologies, is highly prevalent among veterans, especially veterans with posttraumatic stress disorder (PTSD), and poses a major risk for adverse health outcomes, including neurodegeneration and mortality. Given this, we evaluated 1) the association between MetS and neural integrity, indexed by cortical thickness; 2) the relationship between PTSD and MetS; and 3) whether PTSD was associated with cortical thickness indirectly through MetS. METHODS: The sample consisted of 346 U.S. military veterans (89.3% male; 71.4% white) who deployed to Iraq, Afghanistan, or both. Neuroimaging data were available for 274 participants. RESULTS: In whole-brain analyses, MetS was negatively associated with cortical thickness in two left and four right hemisphere regions, as follows: bilateral temporal lobe, including temporal pole, fusiform gyrus, and insula, and extending into occipital cortex (left hemisphere) and orbitofrontal cortex (right hemisphere); bilateral precuneus, posterior cingulate, calcarine, and occipital-parietal cortex; and right rostral anterior cingulate cortex and central sulcus/postcentral gyrus. Path models showed that PTSD predicted MetS (beta = .19, p < .001), which was associated with reduced cortical thickness (beta = -.29 to -.43, all p < .001). CONCLUSIONS: Results from this young veteran sample provide evidence that PTSD confers risk for cardiometabolic pathology and neurodegeneration and raise concern that this cohort may be aging prematurely and at risk for substantial medical and cognitive decline. This study highlights the need to identify the molecular mechanisms linking PTSD to MetS and effective interventions to reduce PTSD-related health comorbidities. PMID- 26826877 TI - Multiplexed detection of lectins using integrated glycan-coated microring resonators. AB - We present the systematic design, fabrication, and characterization of a multiplexed label-free lab-on-a-chip biosensor using silicon nitride (SiN) microring resonators. Sensor design is addressed through a systematic approach that enables optimizing the sensor according to the specific noise characteristics of the setup. We find that an optimal 6 dB undercoupled resonator consumes 40% less power in our platform to achieve the same limit-of-detection as the conventional designs using critically coupled resonators that have the maximum light-matter interaction. We lay out an optimization framework that enables the generalization of our method for any type of optical resonator and noise characteristics. The device is fabricated using a CMOS-compatible process, and an efficient swabbing lift-off technique is introduced for the deposition of the protective oxide layer. This technique increases the lift-off quality and yield compared to common lift-off methods based on agitation. The complete sensor system, including microfluidic flow cell and surface functionalization with glycan receptors, is tested for the multiplexed detection of Aleuria Aurantia Lectin (AAL) and Sambucus Nigra Lectin (SNA). Further analysis shows that the sensor limit of detection is 2 * 10(-6) RIU for bulk refractive index, 1 pg/mm(2) for surface-adsorbed mass, and ~ 10 pM for the glycan/lectins studied here. PMID- 26826876 TI - Addiction-like Synaptic Impairments in Diet-Induced Obesity. AB - BACKGROUND: There is increasing evidence that the pathological overeating underlying some forms of obesity is compulsive in nature and therefore contains elements of an addictive disorder. However, direct physiological evidence linking obesity to synaptic plasticity akin to that occurring in addiction is lacking. We sought to establish whether the propensity to diet-induced obesity (DIO) is associated with addictive-like behavior, as well as synaptic impairments in the nucleus accumbens core considered hallmarks of addiction. METHODS: Sprague Dawley rats were allowed free access to a palatable diet for 8 weeks then separated by weight gain into DIO-prone and DIO-resistant subgroups. Access to palatable food was then restricted to daily operant self-administration sessions using fixed ratio 1, 3, and 5 and progressive ratio schedules. Subsequently, nucleus accumbens brain slices were prepared, and we tested for changes in the ratio between alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N methyl-D-aspartate currents and the ability to exhibit long-term depression. RESULTS: We found that propensity to develop DIO is linked to deficits in the ability to induce long-term depression in the nucleus accumbens, as well as increased potentiation at these synapses as measured by AMPA/N-methyl-D-aspartate currents. Consistent with these impairments, we observed addictive-like behavior in DIO-prone rats, including 1) heightened motivation for palatable food; 2) excessive intake; and 3) increased food seeking when food was unavailable. CONCLUSIONS: Our results show overlap between the propensity for DIO and the synaptic changes associated with facets of addictive behavior, supporting partial coincident neurological underpinnings for compulsive overeating and drug addiction. PMID- 26826878 TI - [Prevalence of sedentary behavior and its correlates among primary and secondary school students]. AB - OBJECTIVE: To determine the students' exposure to four different sedentary behavior (SB) indi-cators and their associations with gender, grade, age, economic status and physical activity level. METHODS: A cross-sectional study was conducted in 2013. The SB was collected using the HELENA instrument, composed by screen time questions (TV, video games and internet) and sitting activ-ities on school opposite shift. The cut point of >=2h/day was used to categorize the outcome. The Poisson regression was used for associations between the outcome and the independent variables (95% significance level), controlling for confounding variables and the possible design effect. RESULTS: The sample was composed by 8661 students. The overall prevalence of SB was 69.2% (CI95% 68.1-70.2) on weekdays, and 79.6% (CI95% 78.7-80.5) on weekends. Females were more associated with the outcome, except to electronic games. Advanced grades students were more involved in sitting tasks when compared to the early grades. Older students were more likely to surf on net for >=2h/day. Higher economic level students were more likely to engage in video games and internet. Active individuals were less likely to engage in SB on weekdays. CONCLUSIONS: The prevalence of SB was high, mainly on weekends. The associations with sex, age, grade and physical activity level should be considered into elaboration of more efficient interventions on SB control. PMID- 26826880 TI - Acquired Symmetric Facial Hyperpigmentation. PMID- 26826879 TI - [Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study]. AB - OBJECTIVE: To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes melito. METHODS: 40 patients with type 1 diabetes melito (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). RESULTS: Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15-40 patients have severe hypoglycemic events versus 5-40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. CONCLUSIONS: This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. PMID- 26826881 TI - Sweet Syndrome: A Review and Update. AB - Sweet syndrome is the most representative entity of febrile neutrophilic dermatoses. It typically presents in patients with pirexya, neutrophilia, painful tender erytomatous papules, nodules and plaques often distributed asymmetrically. Frequent sites include the face, neck and upper extremities. Affected sites show a characteristical neutrophilic infiltrate in the upper dermis. Its etiology remains elucidated, but it seems that can be mediated by a hypersensitivity reaction in which cytokines, followed by infiltration of neutrophils, may be involved. Systemic corticosteroids are the first-line of treatment in most cases. We present a concise review of the pathogenesis, classification, diagnosis and treatment update of this entity. PMID- 26826882 TI - Process of Care for Patients With Benign Cysts and Tumors: Consensus Document of the Andalusian Regional Section of the Spanish Academy of Dermatology and Venereology (AEDV). AB - Benign skin lesions are a common reason for visits to primary care physicians and dermatologists. However, access to diagnosis and treatment for these lesions varies considerably between users, primarily because no explicit or standardized criteria for dealing with these patients have been defined. Principally with a view to reducing this variability in the care of patients with benign cysts or tumors, the Andalusian Regional Section of the Spanish Academy of Dermatology and Venereology (AEDV) has created a Process of Care document that describes a clinical pathway and quality-of-care characteristics for each action. This report also makes recommendations for decision-making with respect to lesions of this type. PMID- 26826883 TI - Neurofibromatosis type 2 service delivery in England. AB - Neurofibromatosis type 2 (NF2) is a complex disease characterized by the development of multiple schwannomas, especially vestibular schwannomas, as well as other types of benign tumours including meningioma and spinal ependymoma. Due to its multisystem nature, the management of NF2 requires a multidisciplinary approach. In England, the delivery of care for NF2 patients has been centralized to four-"hub" centres in Manchester, Cambridge, Oxford and London each having associated "spoke" centres. Each centre has a core multidisciplinary team consisting of genetics, otolaryngology, neurosurgery, paediatrics, neurology, audiology, radiology, psychology, physiotherapy, specialist nurses and administrative staff. In addition, the core team has access to plastic surgery, ophthalmology, peripheral nerve surgery and adult and paediatric oncology. There are weekly multidisciplinary clinics each with six to eight patients. Each patient is discussed during a team meeting and the management decisions that are made are then discussed with the patients. All patients are reviewed at least annually and have annual head magnetic resonance imaging (MRI) and three yearly spinal MRI. Annual audiological assessment is performed. Cochlear implantation and auditory brainstem implantation are offered if indicated. Surgery, stereotactic radiosurgery and bevacizumab therapy are available for the management of intracranial and spinal tumours. The integration of the service in England has provided significant benefits to patient care and, in the long term, will provide robust patient outcome data that will provide an evidence base to assist in optimizing management of patients with NF2. PMID- 26826884 TI - Clinical Phenotypes and Genotypic Spectrum of Cystic Fibrosis in Chinese Children. AB - OBJECTIVES: To characterize the clinical phenotypes and genotypic spectrum of cystic fibrosis (CF) in Chinese children. STUDY DESIGN: We recruited and characterized the phenotypes of 21 Chinese children with CF. All 27 exons and their flanking sequences of the CF transmembrane conductance regulator gene were amplified and sequenced to define the genotypes. RESULTS: Bronchiectasis (95.2%) and sinusitis (76.2%) were the most common clinical presentations among our patients. By contrast, pancreatic insufficiency was rare (14.3%). The predominant organism found in the airways was Pseudomonas aeruginosa (66.7%). There were obvious reductions of forced expiratory volume in the first second (mean +/- SD: 71.8% +/- 17.2% predicted) and forced expiratory flows at 75% of exhaled vital capacity (33.7% +/- 20.4% predicted) in children with CF. Overall, we identified 22 different mutations, including 12 missense, 5 nonsense, 2 frameshift, 1 in frame insertion, 1 splice site, and 1 3'untranslated region mutation. Of these, 7 were novel observations (W216X[780G->A], 1092insA, Q359X, D567Y, 2623-126T->C, 3439delA and 4575+110C->G), and the most common types were L88X and I556V. One de novo mutation (1092insA) was also revealed. Except for N1303K and R334W, none of them were present in the common Caucasian CF transmembrane conductance regulator mutation-screening panels. CONCLUSIONS: There was a 5.7-year delay between the first clinical presentation and the eventual CF diagnosis, suggesting that CF may be underdiagnosed in China. The clinical phenotypes and genotypic spectrum are different from that observed in Caucasians. PMID- 26826885 TI - Epidemiology of Dizziness and Balance Problems in Children in the United States: A Population-Based Study. AB - OBJECTIVE: To study national prevalence of dizziness and balance problems in US children and explore associated risk factors and patterns of healthcare utilization. STUDY DESIGN: A multistage, nationally representative, probability sample of children (n = 10,954; aged 3-17 years) was examined based on the 2012 National Health Interview Survey Child Balance Supplement. Parents were asked if during the past year their child was bothered by symptoms of dizziness and balance problems: vertigo (motion sensation), light-headedness/fainting, clumsiness/poor coordination, poor balance/unsteadiness when standing-up or walking, frequent falls, or other dizziness and balance problems. Logistic regression was used to examine associations with sociodemographic information, birth weight, developmental delays, and significant health conditions. RESULTS: Prevalence of dizziness and balance problems was 5.3% (3.3 million US children); females, 5.7%, males, 5.0%. Non-Hispanic white (6.1%) had increased prevalence compared with Hispanic (4.6%) and non-Hispanic black (4.3%) children, P = .01. Prevalence increased with age, from 4.1% for children aged 3-5 years to 7.5% for children aged 15-17 years, P < .001. Even though the majority had symptoms rated as "no problem" or "a small problem," 18.6% (600,000 US children) had symptoms rated as "moderate," "big," or "very big" problems. Overall, 36.0% of children with dizziness and balance problems were seen by healthcare professionals during the past year and 29.9% received treatment. Among children with dizziness and balance problems rated as moderate/big/very big problems, 71.6% had seen healthcare professionals and 62.4% received treatment for dizziness and balance problems. CONCLUSIONS: The risk factors identified provide useful epidemiologic information about dizziness and balance problems in children and will be used in tracking the Healthy People 2020 goal to increase utilization of healthcare services for these children. PMID- 26826886 TI - Hospitalization for Varicella and Zoster in Children with Inflammatory Bowel Disease. AB - OBJECTIVE: To evaluate the association between inflammatory bowel disease (IBD) and varicella- and herpes zoster-related pediatric hospitalizations. STUDY DESIGN: We performed a cross-sectional inpatient study using the triennial Healthcare Cost and Utilization Project Kids' Inpatient Database for years 1997 2012 to evaluate the association between a secondary diagnosis of IBD and a primary diagnosis of varicella or herpes zoster for hospitalized children ages 5 20 years. Billing codes were used to identify varicella, herpes zoster, ulcerative colitis, Crohn's disease, and other immunocompromising conditions. A logistic regression model was fitted to quantify the odds of varicella or zoster between these categories. RESULTS: There were 8 828 712 weighted admissions meeting the study criteria, 4434 with varicella and 4488 with herpes zoster. There was an association of IBD and immunocompromising conditions with hospitalization for varicella and herpes zoster. This association was stronger among children with Crohn's disease (varicella OR, 12.75; 95% CI, 8.30-19.59; zoster OR, 7.91; 95% CI, 5.60-11.18) compared with children with ulcerative colitis (varicella OR 4.25; 95% CI 1.98-9.12, zoster OR 3.90; 95% CI 1.98-7.67). CONCLUSIONS: IBD in children is associated with hospitalizations for varicella and herpes zoster. These results highlight the importance of efforts to vaccinate patients with IBD without varicella immunity, ideally before the initiation of immunosuppressive therapy. Furthermore, research is needed on the safety and efficacy of the varicella vaccine in children with IBD on immunomodulators or biologic therapy. PMID- 26826887 TI - How robust is ACTIVLIM for the follow-up of activity limitations in patients with neuromuscular diseases? AB - This study aims to investigate the clinimetric properties of ACTIVLIM, a measure of activity limitations, when it is used in daily practice in a large nationwide representative cohort of patients with neuromuscular diseases. A cohort of 2986 patients was assessed at least once over 2 years in 6 national neuromuscular diseases reference centers. Successive Rasch analyses were conducted in order to investigate the scale validity, reliability, consistency across demographic and clinical sub-groups and its sensitivity to change. ACTIVLIM confirmed excellent fit to a unidimensional scale, with stable but 3-times more accurate item calibrations compared to the original publication. It showed a good reliability (R = 0.95), an appropriate targeting for 87% of the sample and an excellent invariance across age, gender, language and time. Despite some variations in the item difficulty hierarchy across diagnoses, ACTIVLIM exhibited a good capability to quantify small but significant changes in activity for various diagnostic groups. Overall, ACTIVLIM demonstrated very good clinimetric properties, allowing accurate quantitative measurement of activity limitations in both children and adults with a variety of neuromuscular diseases. PMID- 26826888 TI - Pancreatic neuroendocrine tumour: Correlation of apparent diffusion coefficient or WHO classification with recurrence-free survival. AB - PURPOSE: To evaluate the correlation between grade of pancreatic neuroendocrine tumours (pNETs) based on the 2010 World Health Organization (WHO) classification and the apparent diffusion coefficient (ADC), and to assess whether the ADC value and WHO classification can predict recurrence-free survival (RFS) after surgery for pNETs. METHODS: This retrospective study was approved by the Institutional Review Board. The requirement for informed consent was waived. Between March 2009 and November 2014, forty-nine patients who underwent magnetic resonance (MR) imaging with diffusion-weighted image and subsequent surgery for single pNETs were included. Correlations among qualitative MR imaging findings, quantitative ADC values, and WHO classifications were assessed. An ordered logistic regression test was used to control for tumour size as a confounding factor. The association between ADC value (or WHO classification) and RFS was analysed. RESULTS: All tumors (n=49) were classified as low- (n=29, grade 1), intermediate- (n=17, grade 2), and high-grade (n=3, grade 3), respectively. The mean ADC of pNETs was moderately negatively correlated with WHO classification before and after adjustment for tumour size (rho=-0.64, p<0.001 and rho=-0.55, p=0.001 respectively). RFS was significantly associated with WHO classification (p=0.007), but not with the ADC value (p=0.569). CONCLUSION: The ADC value of pNETs is moderately correlated with WHO tumour grade, regardless of tumour size. However, the WHO tumour classification of pNET may be more suitable for predicting RFS than the ADC value. PMID- 26826889 TI - The utility of dermoscopy-guided histologic sectioning for the diagnosis of melanocytic lesions: A case-control study. AB - BACKGROUND: Dermoscopy allows for visualization of morphologic structures beyond the epidermis, including features that may indicate early malignant transformation. However, dermoscopic features are rarely considered during routine histologic sectioning, and areas of clinical concern may be missed during microscopic evaluation. OBJECTIVE: We assessed the diagnostic impact of a dermoscopy-guided micropunch score for the evaluation of melanocytic lesions. METHODS: In this case-control study, we evaluated 150 scored melanocytic lesions. Original tissue specimens were reprocessed to create a control group, in which a new score was introduced elsewhere in the lesion to guide an alternative plane of section. Slides were reviewed in a randomized, double-blinded manner to assess histologic features and render a diagnosis. Dermoscopy was also reviewed. RESULTS: The proportion of cases with a higher grade in the original, dermoscopy guided section was statistically significant. Four invasive melanomas were exclusively identified using the scoring protocol. The presence of regression structures, negative pigment network, radial streaming or pseudopods, and irregular blotches were highly specific for a higher diagnostic grade. LIMITATIONS: This study is retrospective and reprocessing tissue does not perfectly mimic routine sectioning. CONCLUSION: Dermoscopy can identify important, histologically high-grade areas, and this information can be used to optimize the sectioning of melanocytic neoplasms. PMID- 26826891 TI - YouTube TM videos related to e-cigarette safety and related health risks: implications for preventing and emerging epidemic. PMID- 26826890 TI - Spanish Compliance With Guidelines for Prescribing Four Drugs in the Intensive Phase of Standard Tuberculosis Treatment. AB - INTRODUCTION: International and Spanish guidelines recommend a 4-drug regimen in the intensive treatment of tuberculosis (TB). The aim of our study was to determine if these recommendations are followed in Spain, and the factors associated with the use of 3 drugs (standard regimen without ethambutol). METHODOLOGY: Observational, multicenter, retrospective analysis of data from patients diagnosed with TB in practically all Spanish Autonomous Communities between 2007 and 2102. Factors associated with the use of 3 drugs were analyzed using logistic regression, and odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated. RESULTS: A total of 3,189 patients were included, 1,413 (44.3%) of whom received 3 drugs. The percentage of 3-drug users among patients with positive sputum smear was 41.2%; among patients with resistance to at least 1 drug, 36.1%; among HIV-infected patients, 31.4%; and among immigrants, 24.8%. Factors associated with the use of 3 drugs were: female sex (OR=1.18; CI: 1.00-1.39); native Spanish (OR=3.09; CI: 2.58-3.70); retired (OR=1.42; CI: 1.14 1.77); homeless (OR=3.10; CI: 1.52-6.43); living alone (OR=1.62; CI: 1.11-2.36); living in a family (OR=1.97; CI: 1.48-2.65); seen by specialists in the region (OR=1.37; CI: 1.10;1.70); no HIV infection (OR=1.63; CI: 1.09-2.48); and negative sputum smear with positive culture (OR=1.59; CI: 1.25-2.02). CONCLUSIONS: A large proportion of TB patients receive intensive treatment with 3 drugs. TB treatment recommendations should be followed, both in routine clinical practice and by the National Plan for Prevention and Control of Tuberculosis in Spain. PMID- 26826892 TI - [Atypical presentation of central serous choroidopathy. Case report]. AB - BACKGROUND: Central serous choroidopathy is a macular disease, usually with a self-limited and benign course, and predominantly affects male patients between 20 and 45 years old. CLINICAL CASE: A 68 year-old female patient complained of decreased visual acuity of her right eye of approximately 3 weeks of onset. Best corrected visual acuity in her right eye was 20/100. Fundus examination revealed a macular serous detachment involving its centre, as well as the presence of multiple calcified drusen. Fluorescein angiography showed late parafoveal leakage in a "smokestack" pattern in the right macular area. Optical coherence tomography showed a dome-shape macular detachment, also in the right eye. The patient was observed every 2 weeks and spontaneous resolution of the macular detachment was seen a month later. Based on these clinical features, a diagnosis was made of central serous choroidopathy of atypical presentation. CONCLUSIONS: Atypical presentation cases of serous central choroidopathy might be seen occasionally. Hence, it is an important differential diagnosis of age related macular degeneration in patients older than 60 years. PMID- 26826893 TI - Autism traits: The importance of "co-morbid" problems for impairment and contact with services. Data from the Bergen Child Study. AB - BACKGROUND: Co-occurring problems are common in individuals with clinical autism spectrum disorder (ASD) but their relevance for impairment and contact with health services in ASD is largely unexplored. AIMS: We investigated the extent of co-occurring problems in children with high ASD traits from a total population sample. We explored the contribution of co-occurring problems to impairment and service contact, and whether there were children without co-occurring problems in this group; as proxy for "ASD only". METHODS AND PROCEDURES: Children screening positive on the Autism Spectrum Screening Questionnaire (ASSQ) were used as proxy for ASD. Attention Deficit/Hyperactivity Disorder (ADHD) and Oppositional Defiant Disorder (ODD) were operationalised using symptom counts. A parent or teacher report above the 95th percentile counted as "problem" present for other symptom domains. OUTCOMES AND RESULTS: 92% of ASSQ high-scorers had a minimum of two other problems. Emotional problems, ADHD symptoms and learning problems were the most commonly reported problems, also predicting impairment and contact with services. CONCLUSIONS AND IMPLICATIONS: Co-occurring problems were common in ASD screen positive children and contributed strongly to both impairment and to contact with services. Gender differences indicated that female symptoms were perceived as less impairing by parents and teachers. PMID- 26826894 TI - Quantitative Assessment of Vectorcardiographic Loop Morphology. AB - Vectorcardiography (VCG), developed 100years ago, characterizes clinically important electrophysiological properties of the heart. In this study, VCG QRS loop roundness, planarity, thickness, rotational angle, and dihedral angle were measured in 81 healthy control subjects (39.0+/-14.2y; 51.8% male; 94% white), and 8 patients with infarct-cardiomyopathy and sustained monomorphic ventricular tachycardia (VT) (68.0+/-7.8y, 37.5% male). The angle between two consecutive QRS vectors was defined as the rotational angle, while dihedral angle quantified planar alteration over the QRS loop. In VT subjects, planarity index decreased (0.63+/-0.22 vs. 0.88+/-0.10; P=0.014), and dihedral angle was significantly more variable (variance of dihedral angle, median (IQR): 897(575-1450) vs. 542(343 773); P=0.029; rMSSD: 47.7+/-12.7 vs. 35.1+/-13.1; P=0.027). Abnormal electrophysiological substrate in VT patients is characterized by the appearance of QRS loop folding, likely due to local conduction block. The presence of fragmented QRS complexes on the 12-lead ECG had low sensitivity (31%) for detecting QRS loop folding on the VCG. PMID- 26826895 TI - Decreased interhemispheric functional connectivity in insula and angular gyrus/supramarginal gyrus: Significant findings in first-episode, drug-naive somatization disorder. AB - Neuroimaging data have demonstrated brain functional alterations in patients with somatization disorder (SD). However, there is little information on interhemispheric resting-state functional connectivity (FC) in SD. In this study, resting-state functional magnetic resonance imaging (fMRI) and voxel-mirrored homotopic connectivity (VMHC) were applied to examine the changes of interhemispheric FC of the whole brain in patients with SD. A total of 25 first episode, medication-naive SD patients and 28 age-, sex-, education-matched healthy controls (HC) underwent resting-state fMRI, and the data were analyzed by VMHC. Compared with HC, patients had lower VMHC in the angular gyrus/supramarginal gyrus (AG/SG) and insula. The reproducibility of the results was validated using the split-half and leave-one-out validations. No significant correlation was found between the VMHC in AG/SG or insula and clinical variables. Our findings indicate that the interhemispheric FC in the AG/SG and insula is decreased in first-episode, treatment-naive patients with SD, and thus provide new insight for disruption of interhemispheric FC in the pathophysiological mechanism of SD. PMID- 26826896 TI - [Intracardiac catheter migration revealed by an ischemic stroke]. PMID- 26826897 TI - Secondary prevention program for osteoporotic fractures at Lille University Hospital. PMID- 26826898 TI - Young people's difficulty in talking to others about mental health problems: An analysis of time trends in Switzerland. AB - The article aimed to analyse time trends regarding young people's willingness to talk about mental health problems. Data on 16,774 participants (16-20-year olds) of the 'Swiss Multicentre Adolescent Survey on Health' (SMASH) were analysed. The survey was conducted in 1992/93 and in 2002. Logistic regression analyses were conducted to identify predictors associated with the self-reported willingness of youth to talk about mental health problems with adults (other than parents), friends or no one. Socio-demographic characteristics were used as covariates. These analyses were first carried out for the total sample and, in a second step, stratified by suicidality of the participants. The percentage of participants who would talk about mental health problems with adults or friends increased between 1992/93 and 2002, while the percentage of those who would not talk about such problems decreased. This pattern was confirmed in the stratified analyses (i.e., for suicidal and non-suicidal individuals). Hence, Swiss youth seem to have less difficulty in talking with others about mental health problems than previous cohorts. This trend towards increased disclosure may have implications for claims that the prevalence of mental health problems has increased in recent decades. PMID- 26826900 TI - Prosodic analysis of neutral, stress-modified and rhymed speech in patients with Parkinson's disease. AB - BACKGROUND AND OBJECTIVE: Hypokinetic dysarthria (HD) is a frequent speech disorder associated with idiopathic Parkinson's disease (PD). It affects all dimensions of speech production. One of the most common features of HD is dysprosody that is characterized by alterations of rhythm and speech rate, flat speech melody, and impairment of speech intensity control. Dysprosody has a detrimental impact on speech naturalness and intelligibility. METHODS: This paper deals with quantitative prosodic analysis of neutral, stress-modified and rhymed speech in patients with PD. The analysis of prosody is based on quantification of monopitch, monoloudness, and speech rate abnormalities. Experimental dataset consists of 98 patients with PD and 51 healthy speakers. For the purpose of HD identification, sequential floating feature selection algorithm and random forests classifier is used. In this paper, we also introduce a concept of permutation test applied in the field of acoustic analysis of dysarthric speech. RESULTS: Prosodic features obtained from stress-modified reading task provided higher classification accuracies compared to the ones extracted from reading task with neutral emotion demonstrating the importance of stress in speech prosody. Features calculated from poem recitation task outperformed both reading tasks in the case of gender-undifferentiated analysis showing that rhythmical demands can in general lead to more precise identification of HD. Additionally, some gender related patterns of dysprosody has been observed. CONCLUSIONS: This paper confirms reduced variation of fundamental frequency in PD patients with HD. Interestingly, increased variability of speech intensity compared to healthy speakers has been detected. Regarding speech rate disturbances, our results does not report any particular pattern. We conclude further development of prosodic features quantifying the relationship between monopitch, monoloudness and speech rate disruptions in HD can have a great potential in future PD analysis. PMID- 26826899 TI - The relationship between tics, OC, ADHD and autism symptoms: A cross- disorder symptom analysis in Gilles de la Tourette syndrome patients and family-members. AB - Gilles de la Tourette's syndrome (GTS) is a disorder in which obsessive compulsive (OC), Attention Deficit Hyperactivity Disorder (ADHD) and autism symptoms occur in up to 60% of patients, suggesting shared etiology. We explored the phenotypic structure of tic, OC, ADHD, and autism symptoms as measured by the YGTSS,Y-BOCS,CAARS and AQ, in 225 GTS patients and 371 family members. First, Confirmatory Factor Analyses (CFA) were performed on the symptom structure of each separate symptom scale. Second, the symptom dimensions derived from each scale were combined in one model, and correlations between them were calculated. Using the correlation matrix, Exploratory Factor Analyses (EFA) were performed on the symptom dimensions across the scales. EFA revealed a five factor structure: tic/aggression/symmetry; OC symptoms/compulsive tics/ numbers and patterns; ADHD symptoms; autism symptoms; and hoarding/inattention symptoms. The results are partly in line with the traditional categorical boundaries of the symptom scales used, and partly reveal a symptom structure that cuts through the diagnostic categories. This phenotypic structure might more closely reflect underlying etiologies than a structure that classically describes GTS patients according to absence or presence of comorbid OCD, ADHD and autism, and might inform both future genetic and treatment studies. PMID- 26826901 TI - Representation learning for mammography mass lesion classification with convolutional neural networks. AB - BACKGROUND AND OBJECTIVE: The automatic classification of breast imaging lesions is currently an unsolved problem. This paper describes an innovative representation learning framework for breast cancer diagnosis in mammography that integrates deep learning techniques to automatically learn discriminative features avoiding the design of specific hand-crafted image-based feature detectors. METHODS: A new biopsy proven benchmarking dataset was built from 344 breast cancer patients' cases containing a total of 736 film mammography (mediolateral oblique and craniocaudal) views, representative of manually segmented lesions associated with masses: 426 benign lesions and 310 malignant lesions. The developed method comprises two main stages: (i) preprocessing to enhance image details and (ii) supervised training for learning both the features and the breast imaging lesions classifier. In contrast to previous works, we adopt a hybrid approach where convolutional neural networks are used to learn the representation in a supervised way instead of designing particular descriptors to explain the content of mammography images. RESULTS: Experimental results using the developed benchmarking breast cancer dataset demonstrated that our method exhibits significant improved performance when compared to state-of-the-art image descriptors, such as histogram of oriented gradients (HOG) and histogram of the gradient divergence (HGD), increasing the performance from 0.787 to 0.822 in terms of the area under the ROC curve (AUC). Interestingly, this model also outperforms a set of hand-crafted features that take advantage of additional information from segmentation by the radiologist. Finally, the combination of both representations, learned and hand-crafted, resulted in the best descriptor for mass lesion classification, obtaining 0.826 in the AUC score. CONCLUSIONS: A novel deep learning based framework to automatically address classification of breast mass lesions in mammography was developed. PMID- 26826902 TI - Multimodal analysis of startle type responses. AB - BACKGROUND AND OBJECTIVE: This article presents a multimodal analysis of startle type responses using a variety of physiological, facial, and speech features. These multimodal components of the startle type response reflect complex brain body reactions to a sudden and intense stimulus. Additionally, the proposed multimodal evaluation of reflexive and emotional reactions associated with the startle eliciting stimuli and underlying neural networks and pathways could be applied in diagnostics of different psychiatric and neurological diseases. Different startle type stimuli can be compared in the strength of their elicitation of startle responses, i.e. their potential to activate stress-related neural pathways, underlying biomarkers and corresponding behavioral reactions. METHODS: An innovative method for measuring startle type responses using multimodal stimuli and multimodal feature analysis has been introduced. Individual's multimodal reflexive and emotional expressions during startle type elicitation have been assessed by corresponding physiological, speech and facial features on ten female students of psychology. Different startle eliciting stimuli like noise and airblast probes, as well as a variety of visual and auditory stimuli of different valence and arousal levels, based on International Affective Picture System (IAPS) images and/or sounds from International Affective Digitized Sounds (IADS) database, have been designed and tested. Combined together into more complex startle type stimuli, such composite stimuli can potentiate the evoked response of underlying neural networks, and corresponding neurotransmitters and neuromodulators as well; this is referred to as increased power of response elicitation. The intensity and magnitude of multimodal responses to selected startle type stimuli have been analyzed using effect sizes and medians of dominant multimodal features, i.e. skin conductance, eye blink, head movement, speech fundamental frequency and energy. The significance of the observed effects and comparisons between paradigms were evaluated using one tailed t-tests and ANOVA methods, respectively. Skin conductance response habituation was analyzed using ANOVA and post hoc multiple comparison tests with the Dunn-Sidak correction. RESULTS: The results revealed specific physiological, facial and vocal reflexive and emotional responses on selected five stimuli paradigms which included: (1) acoustic startle probes, (2) airblasts, (3) IAPS images, (4) IADS sounds, and (5) image-sound-airblast composite stimuli. Overall, composite and airblast paradigms resulted in the largest responses across all analyzed features, followed by sound and acoustic startle paradigms, while paradigm using images consistently elicited the smallest responses. In this context, power of response elicitation of the selected stimuli paradigms can be described according to the aggregated magnitude of the participants' multimodal responses. We also observed a habituation effect only in skin conductance response to acoustic startle, airblast and sound paradigms. CONCLUSIONS: This study developed a system for paradigm design and stimuli generation, as well as real-time multimodal signal processing and feature calculation. Experimental paradigms for monitoring individual responses to stressful startle type stimuli were designed in order to compare the response elicitation power across various stimuli. The developed system, applied paradigms and obtained results might be useful in further research for evaluation of individuals' multimodal responses when they are faced with a variety of aversive emotional distractors and stressful situations. PMID- 26826903 TI - Selective sensitization of C-fiber nociceptors by hydrogen sulfide. AB - We examined the effects of intraplantar (i.pl.) administration of NaHS, an H2S donor, known to cause T-type Ca(2+) channel (T-channel)-dependent mechanical hyperalgesia, on responsiveness to electric stimulation with 5, 250 and 2000 Hz sine waves (SW) that selectively excites C, Adelta and Abeta fibers, respectively. NaHS, given i.pl., caused behavioral hypersensitivity to SW stimulation at 5 Hz, but not 250 or 2000 Hz, in rats. NaHS also enhanced phosphorylation of spinal ERK following 5 Hz SW stimulation. Three distinct T channel blockers abolished the NaHS-induced behavioral hypersensitivity to 5 Hz SW stimulation. Thus, H2S selectively sensitizes C-fiber nociceptors via T channels. PMID- 26826904 TI - Outcome and risk of recurrence for endoscopic resection of colonic superficial neoplastic lesions over 2 cm in diameter. AB - BACKGROUND: Large colorectal superficial neoplastic lesions are challenging to remove. This study aimed to assess the outcomes of routine endoscopic resection of large (>=2 cm and <3 cm) and giant (>=3 cm) lesions. METHODS: From 4587 endoscopic resections, 265 (5.7%) large and giant lesions were removed in 249 patients. We retrospectively analyzed 125 patients (141 endoscopic mucosal resection, 73 large and 68 giant lesions) with a follow-up of 6-12 months. Rate of en bloc and piecemeal resection, recurrence and risk factors were analyzed. RESULTS: En bloc was performed in 92 cases (65.2%) and piecemeal resection in 49 (34.8%). A complete endoscopic resection was achieved in 139 cases (98.5%) with radical resection in 84/139 cases (60.4%). Argon plasma coagulation was applied in 18/141 lesions (12.8%). A recurrence occurred in 16/139 lesions (11.5%). The risk of recurrence at one year was significantly higher for giant than large lesions (p=0.03). The recurrence risk was higher in treated than in non-argon plasma coagulation treated lesions (p=0.01). CONCLUSIONS: endoscopic mucosal resection is a safe and effective routine treatment for large superficial neoplastic lesions. The risk factors for recurrence include giant size, non protruding morphology, piecemeal technique and argon plasma coagulation. PMID- 26826905 TI - Celiac disease in a large cohort of children and adolescents with recurrent headache: A retrospective study. AB - BACKGROUND: The clinical picture of celiac disease is changing with the emergence of subclinical forms and growing evidence reporting associated neurological disorders. AIMS: To establish the prevalence of celiac disease in children suffering from recurrent headache. METHODS: In our retrospective study we collected charts from 1131 children attending our tertiary care Centre for Paediatric Headache over the period 2001-2012. They were screened for celiac disease and positive patients were referred to our Operative Unit for Coeliac disease and confirmed positive children underwent upper endoscopy with multiple duodenal biopsies. Celiac children started a gluten-free diet. RESULTS: 883 children (481 females; median age, 9.8 years, range 3-19) performed celiac disease screening, and among them, 11 children (7 females; median age, 8.2 years, range: 4.8-13.9) were diagnosed with celiac disease. Seven children (5 females, median age, 11.9 years, range: 10.3-13.9) had been diagnosed as celiac prior to the neurological evaluation. The prevalence of celiac disease in our sample is 2.04% vs. 1.2% of the general population (p=0.034). CONCLUSIONS: Our study demonstrates, on a large series, that celiac disease prevalence is doubled in patients with chronic headache. Screening for celiac disease could be advised as part of the diagnostic work-up in these paediatric patients, particularly among pharmacological non-responders. PMID- 26826906 TI - NICE guidance on nintedanib for treating idiopathic pulmonary fibrosis. PMID- 26826907 TI - Abel Ayerza. PMID- 26826908 TI - Primary Ciliary Dyskinesia. PMID- 26826909 TI - High-throughput analysis of horse sperms' 3D swimming patterns using computational on-chip imaging. AB - Using a high-throughput optical tracking technique that is based on partially coherent digital in-line holography, here we report a detailed analysis of the statistical behavior of horse sperms' three-dimensional (3D) swimming dynamics. This dual-color and dual-angle lensfree imaging platform enables us to track individual 3D trajectories of ~1000 horse sperms at sub-micron level within a sample volume of ~9MUL at a frame rate of 143 frames per second (FPS) and collect thousands of sperm trajectories within a few hours for statistical analysis of their 3D dynamics. Using this high-throughput imaging platform, we recorded >17,000 horse sperm trajectories that can be grouped into six major categories: irregular, linear, planar, helical, ribbon, and hyperactivated, where the hyperactivated swimming patterns can be further divided into four sub-categories, namely hyper-progressive, hyper-planar, hyper-ribbon, and star-spin. The large spatio-temporal statistics that we collected with this 3D tracking platform revealed that irregular, planar, and ribbon trajectories are the dominant 3D swimming patterns observed in horse sperms, which altogether account for >97% of the trajectories that we imaged in plasma-free semen extender medium. Through our experiments we also found out that horse seminal plasma in general increases sperms' straightness in their 3D trajectories, enhancing the relative percentage of linear swimming patterns and suppressing planar swimming patterns, while barely affecting the overall percentage of ribbon patterns. PMID- 26826910 TI - Gonococcal arthritis in human immunodeficiency virus-infected patients. Review of the literature. AB - We report a case of gonococcal arthritis in a patient with human immunodeficiency virus (HIV) infection and review 17 previously published cases; only one patient presented urethritis, and blood cultures were positive in one case. Gonococcal arthritis is rare in HIV-infected patients and is not usually associated with other symptoms. It should be considered in the differential diagnosis of acute arthritis in patients with HIV infection. PMID- 26826911 TI - [Difficulties of the care of public antigen alloimmunization]. AB - Alloimmunization against high-frequency erythrocyte antigens is a problematic situation in terms of laboratory diagnosis, transfusion and obstetrical management. We report the case of a pregnant woman alloimmunized against public Ag. We detail the difficulties of alloantibody (Ab) identification and transfusion management of the deliveries. A 29-year-old pregnant woman was hospitalized in gynecology and obstetrics departments at 36 weeks of gestation for assessment of hydrops fetalis. Antibody identification test revealed the presence of a pan-reactive antibody. Investigations realized in CNRGS (Paris) concluded in anti-GE2+anti-RH3+autoantibody. The red cell phenotype was GE: -2,3. A therapeutic interruption of the pregnancy was indicated. A program of autologous transfusion was organized with withdrawal of 2 units of blood. The 2nd pregnancy took place normally. Before delivery, an autologous blood reserve consisting of 2 red cell packs and 2 fresh frozen plasma was withdrawn and transfused after delivery. The management of anti-public alloimmunization poses several problems. The first one is of diagnostic nature with, on the one hand, the difficulty of Ab identification by the available red cell panels and, on the other hand, the possible presence of alloantibodies of transfusional or obstetric interest masked by anti-public Ab. The second is represented by transfusional care of these patients. In the absence of a national reserve of frozen rare blood, the autologous transfusion remains the only alternative. However, it can answer only a limited number of indications and only in case of moderate blood loss. PMID- 26826912 TI - Measurement of fecal elastase improves performance of newborn screening for cystic fibrosis. AB - BACKGROUND: The aim of newborn screening (NBS) for CF is to detect children with 'classic' CF where early treatment is possible and improves prognosis. Children with inconclusive CF diagnosis (CFSPID) should not be detected, as there is no evidence for improvement through early treatment. No algorithm in current NBS guidelines explains what to do when sweat test (ST) fails. This study compares the performance of three different algorithms for further diagnostic evaluations when first ST is unsuccessful, regarding the numbers of children detected with CF and CFSPID, and the time until a definite diagnosis. METHODS: In Switzerland, CF NBS was introduced in January 2011 using an IRT-DNA-IRT algorithm followed by a ST. In children, in whom ST was not possible (no or insufficient sweat), 3 different protocols were applied between 2011 and 2014: in 2011, ST was repeated until it was successful (protocol A), in 2012 we proceeded directly to diagnostic DNA testing (protocol B), and 2013-2014, fecal elastase (FE) was measured in the stool, in order to determine a pancreas insufficiency needing immediate treatment (protocol C). RESULTS: The ratio CF:CFSPID was 7:1 (27/4) with protocol A, 2:1 (22/10) with protocol B, and 14:1 (54/4) with protocol C. The mean time to definite diagnosis was significantly shorter with protocol C (33days) compared to protocol A or B (42 and 40days; p=0.014 compared to A, and p=0.036 compared to B). CONCLUSIONS: The algorithm for the diagnostic part of the newborn screening used in the CF centers is important and affects the performance of a CF-NBS program with regard to the ratio CF:CFSPID and the time until definite diagnosis. Our results suggest to include FE after initial sweat test failure in the CF-NBS guidelines to keep the proportion of CFSPID low and the time until definite diagnosis short. PMID- 26826914 TI - Comment on: plateaued national utilization of adolescent bariatric surgery despite increasing prevalence of obesity-associated co-morbid diseases. PMID- 26826913 TI - Reversible airway obstruction in cystic fibrosis: Common, but not associated with characteristics of asthma. AB - BACKGROUND: As asthma-like symptoms are common in CF, we evaluated reversible airway obstruction and associated characteristics. METHODS: Retrospective analysis of charts including spirometry and bronchodilator response. RESULTS: Of 190 CF patients (103 at Schneider's, 87 at Hadassah), aged 14.4 (4-76) years, median (range), 39% had reversible obstruction (DeltaFEV1% predicted >=12%), associated with younger age (p=0.01) and severe genotype (p=0.02). There was no association with family history of asthma, serum IgE, blood eosinophils, pancreatic status, FEV1<40% predicted, Aspergillus or pseudomonas infection. Of patients with reversible obstruction, 74% were on bronchodilator and 68% on inhaled corticosteroid therapy but 54% and 57% respectively receiving these therapies did not have reversible obstruction. CONCLUSIONS: Reversible airway obstruction is common in CF, more frequent in younger patients and with severe genotype, with no correlation to markers of atopy or CF clinical severity. Bronchodilator and inhaled corticosteroid therapies are commonly prescribed even without reversible obstruction. PMID- 26826915 TI - Comprehensive assessment of physical functioning in bariatric surgery candidates compared with subjects without obesity. AB - BACKGROUND: Obesity appears to be associated with reduced physical performance, but comprehensive assessments of physical functioning are lacking in subjects with severe obesity, in particular in comparison with subjects without obesity. This precludes an objective assessment of the degree of impairment. OBJECTIVE: To compare motor skills and cardiopulmonary fitness between subjects with severe obesity (OB) (i.e., candidates for bariatric surgery) and control subjects without obesity (non-OB). SETTING: Cantonal Hospital, Switzerland. METHODS: Flexibility, movement speed, balance, maximal isometric strength, and cardiopulmonary fitness were tested in 45 OB (body mass index: 42.6+/-.9 kg/m(2); age: 35+/-1.7 years; 33 women) and 32 non-OB (body mass index: 23+/-.4 kg/m(2); age: 38.5+/-2.1 years; 25 women) subjects. RESULTS: In comparison with the non-OB group, the OB group showed reduced shoulder flexibility (P<.001) but comparable hamstrings flexibility (P = .3). Speed-related tasks (i.e., timed up-and-go test and timed lying-to-standing test) indicated that the OB group was slower than the non-OB group (all P<.007). Strength-related tasks indicated a greater absolute back muscle and knee-extensor strength (all P<.002) in the OB group with no difference in knee-flexor strength (both P>.8). However, when related to weight, the OB group showed reduced maximal strength (all P<.002). Bicycle spiroergometry indicated that absolute oxygen consumption at peak exercise and at the anaerobic threshold did not differ between groups (both P>.06). Related to weight, however, values were lower in the OB than in the non-OB group (both P< .001). CONCLUSION: Data indicate a differential pattern of functional impairment in bariatric surgery candidates compared with subjects without obesity. These findings might help to establish tailored intervention protocols to improve physical performance in such subjects. PMID- 26826916 TI - Outcomes of Roux-en-Y gastric bypass in the super obese: comparison of body mass index 50-60 kg/m(2) and>=60 kg/m(2) with the morbidly obese. AB - BACKGROUND: Reports on the outcomes of Roux-en-Y gastric bypass (RYGB) in super obese patients are limited, especially on patients with body mass index (BMI)>=60 kg/m(2). OBJECTIVES: The aim of the present study was to evaluate and compare the tolerability and efficacy of RYGB in the super-obese by comparing patients with a BMI of 50-60 kg/m(2) and a BMI of>=60 kg/m(2) with patients with a BMI of 40-50 kg/m(2). SETTING: Academic practice. METHODS: Between January 2004 and November 2013, a total of 2717 patients underwent RYGB at our institution. Of these, 661 (24.3%) had a preoperative BMI of 50-60 kg/m(2) and 230 (8.5%) had a BMI>=60 kg/m(2). A retrospective review of outcomes and complications was performed, comparing these patients with 1555 patients with a BMI between 40-50 kg/m(2). RESULTS: Fifty-two (3.3%) patients in the BMI 40-50 kg/m(2) group, 15 (2.3%) patients in the BMI 50-60 kg/m(2) group, and 3 (1.3%) patients in the BMI>=60 kg/m(2) had<30 days of follow-up. Readmission rates were 10.7%, 9.2%, and 11.7%, and reoperation rates were 7.3%, 5.0%, and 6.1%, in the BMI 40-50, 50-60, and>=60 kg/m(2) groups, respectively. No significant difference was found in readmission rate among the 3 groups, and reoperation rate was significantly lower in the BMI 50-60 kg/m(2) group. Mean percentage of excess BMI loss was 58.3%, 80.6%, 85.8%, 83.3%, and 80.9% in the BMI 40-50 kg/m(2) group; 44.9%, 65.0%, 70.1%, 72.1%, and 65.9% in the BMI 50-60 kg/m(2) group; and 38.5%, 57.4%, 62.2%, 62.8%, and 59.1% in the>=60 kg/m(2) group at 6, 12, 18, 24, and 36 months, respectively. The differences in excess BMI loss were statistically significant among all 3 groups at all follow-up time points. All groups experienced a significant decrease in their mean number of co-morbidities after the procedure. CONCLUSION: Readmission and reoperation rates were similar in the BMI 40-50, 50-60, and>=60 kg/m(2) groups. Super-obese and super-super-obese patients are not at greater risk for surgical complications compared with those with lower BMIs. PMID- 26826917 TI - Medico-legal analysis of legal complaints in bariatric surgery: a 15-year retrospective study. AB - BACKGROUND: Bariatric surgery for severe obesity has become an effective and accepted treatment for sustained weight loss. OBJECTIVES: The aim of our study was to analyze the complications and issues raised by the experts on which jury or judges' decisions were made for the different types of bariatric surgery. SETTING: University Hospital, France. MATERIALS AND METHODS: We have carried out a retrospective study of 59 expert review dossiers over a period of 15 years (1999-2014) on the different types of bariatric surgery (laparoscopic adjustable gastric band [LAGB], sleeve gastrectomy [SG], Roux-en-Y gastric bypass [RYGB], vertical banded gastroplasty [VBG], and gastric plication [GP]). RESULTS: Of the cases, 81% were women and the average age was 39 years old (range 19 to 68 years). Among the procedures giving rise to the complaints, 40% were for LAGB, 28% for RYGB, and 23% for SG. The most common initial complications were perforations (30%), fistulae (27%), bowel obstruction (14%), vascular injuries (9.5%), and infections (peritonitis, pleurisy, abscesses, and so forth) (8%). Revision surgery was required in 78% of patients, and perioperative complications accounted for 28.5% of dossiers. The experts concluded that fault had occurred in 40% of case. Negligence arising from an error deemed to be an act of negligence was found in 30% of cases, 67% of which were because of delayed diagnosis. Major long-term complications accounted for 8% of dossiers and minor long-term complications for 22%. Forty-seven percent of patients completely recovered. CONCLUSION: Delayed diagnosis was the main error established by the experts. Surgeons should remain vigilant postoperatively after every bariatric surgical procedure. PMID- 26826918 TI - Effects of gastric banding on glucose tolerance, cardiovascular and renal function, and diabetic complications: a 13-year study of the morbidly obese. AB - BACKGROUND: Limited information is available on weight loss, metabolic control, cardiovascular disease and diabetic complications in morbidly obese patients undergoing gastric banding (LAGB) compared with morbidly obese patients receiving medical treatment. OBJECTIVE: To assess the long-term effects of laparoscopic adjustable gastric banding (LAGB) on glucose tolerance, arterial hypertension, and cardiovascular disease and prevention of diabetic complications (retinopathy and renal function) in morbidly obese patients. SETTING: University hospitals, Italy. MATERIALS AND METHODS: In this retrospective study, 87 morbidly obese patients who underwent LAGB (20 with diabetes) and 87 morbidly obese patients who did not undergo surgery (36 with diabetes) for the treatment of obesity during the period 1995 to 2003 consented for re-examination after a mean (+/-standard deviation) period of 13.8+/-2.04 years. At baseline, all mobidly obese patients had a body mass index (BMI)>=35 kg/m(2) and were aged 18 to 65 years. RESULTS: At follow-up, LAGB patients maintained a lower weight compared with baseline values and demonstrated significant decreases in both blood pressure and heart rate measurements compared with control patients. LAGB patients also experienced greater improvement of glucose tolerance than did control patients (28% versus 10%, respectively; P<.01) and reduction of insulin and homeostasis model assessment for insulin resistance. Fewer LAGB patients developed carotid plaques than did control patients (10% versus 26%, respectively; P<.01). Intensification of antihypertensive therapy was required in 31% of surgery versus 60% of control patients (P<.05). Among diabetic patients, improved glucose tolerance occurred in 55% of surgery patients versus 0% in the control group (P<.01). In addition, insulin treatment was necessary in 9 control patients versus 0 in the surgery group (P<.05), and carotid plaques occurred in 10% of LAGB patients versus 50% of control patients (P<.01). Creatinine levels and the estimated glomerular filtration rate improved in LAGB diabetic patients but not in control patients (P< .05). CONCLUSION: Despite a very small weight loss over the long term (i.e., 2.2 kg/m(2)), improvement of glucose tolerance persisted for long periods after LAGB, with no unfavorable effect on kidney function and retinopathy. In contrast, no effect was observed on prevention of arterial hypertension or cardiovascular disease. PMID- 26826919 TI - Technical factors associated with leaks after laparoscopic gastric bypass. PMID- 26826920 TI - Internal herniation after laparoscopic antecolic Roux-en-Y gastric bypass: a nationwide Danish study based on the Danish National Patient Register. AB - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the most common surgical treatment for morbid obesity in Denmark. Internal herniation (IH) or intermittent internal herniation (IIH) is a major late complication after LRYGB due to persistent mesenteric defects. However, the incidence of IH/IIH is still not known in Denmark. OBJECTIVES: The primary aim of the study was to assess the incidence of IH/IIH after LRYGB performed in the period between 2006 and 2011 with a follow-up until 2013, where mesenteric defects were not routinely closed during the primary operation. SETTING: Department of Bariatric Surgery, Koege University Hospital, Denmark METHODS: We performed a retrospective nationwide analysis of prospectively collected data from all patients with LRYGB performed in Denmark from 2006 to 2011 based on the Danish National Patient Registry (NPR). From January 2006 to December 2011, 12,221 patients underwent an LRYGB procedure in Denmark. Relevant data from all 12,221 patients were retrieved from the NPR during the follow-up period from January 2006 to May 2013; we registered possible subsequent abdominal operations in these patients. RESULTS: Operations were performed on 398 patients because of suspected IH/IIH; 383 of these patients had IH/IIH (3.1%; 95% CI 2.8-3.5). The estimate for the 5-year cumulative incidence of clinically significant cases with IH/IIH was 4%. The median time interval until the onset of IH/IIH after LRYGB was 15 months (range 0-67 months) in a follow-up period with a median of 38 months (range 16-87 months). CONCLUSION: In the period from 2006 to 2011, mesenteric defects were not routinely closed during LRYGB in Denmark. The cumulative 5-year incidence of IH/IIH after LRYGB was 4% in a median follow-up period of 38 months (range 16-87) in Denmark when data was retrieved from the NPR. PMID- 26826921 TI - Robotic sleeve gastrectomy, hiatal hernia repair and anterior fundoplication in a patient with symptomatic GERD. PMID- 26826922 TI - Management of vitamin K deficiency after biliopancreatic diversion with or without duodenal switch. AB - BACKGROUND: Reduced serum vitamin K levels are frequently observed after biliopancreatic diversion (BPD) and BPD with duodenal switch (BPD/DS). The criteria for treatment are not precisely defined. OBJECTIVES: To assess the effects of standardized vitamin K supplementation in patients who develop vitamin K deficiency after BPD or BPD/DS. SETTING: Teaching hospital specializing in bariatric surgery. METHODS: Serum vitamin K levels, clotting times, and vitamin K dependent coagulation factors were measured after an overnight fast at baseline and then at 4 days and 1, 4, and 52 weeks after the start of vitamin K supplementation in 10 consecutive patients who had developed severe vitamin K deficiency after BPD or BPD/DS. Vitamin K was administered in a dose of 5 mg/d for 1 week, followed by a maintenance dose of 5 mg once a week. RESULTS: At baseline, all patients had serum vitamin K1 levels below the limit of detection, but none reported symptoms of easy bleeding. Minor prolongation of the prothrombin time and minimal decreases of some coagulation factors were observed in a minority of patients. During the first week of vitamin K loading, median serum vitamin K1 levels rose into the high normal range. During maintenance treatment, median vitamin K1 levels settled in the low normal range. CONCLUSION: Vitamin K1 deficiency in patients with BPD or BPD/DS is not commonly associated with bleeding or clinically relevant decreases in coagulation factor activity. We hypothesize that vitamin K2 production in the large intestine is usually sufficient to compensate for vitamin K1 deficiency and to maintain total liver vitamin K stores within the range required for (near) normal coagulation factor production. PMID- 26826923 TI - Decreased visceral fat area correlates with improved arterial stiffness after Roux-en-Y gastric bypass in Chinese obese patients with type 2 diabetes mellitus: a 12-month follow-up. AB - BACKGROUND: Associations between demographic data and arterial stiffness have not been examined adequately in Chinese obese patients with type 2 diabetes (T2DM) who underwent Roux-en-Y gastric bypass (RYGB). OBJECTIVE: This study was designed to examine changes in body fat distribution and metabolic parameters after RYGB and whether these changes correlated with improved arterial stiffness. SETTING: The study was performed at the authors' academic university-affiliated hospital. METHODS: A retrospective review of 42 Chinese patients with a diagnosis of obesity and T2DM and 22 health controls was conducted, focusing on metabolic outcomes and aortic pulse wave velocity (PWV) before and 12 months after RYGB. RESULTS: At baseline, PWV in the study group was significantly greater than in the control group (6.9+/-1.5 versus 5.8+/-.6 ms, respectively; P<.01). PWV was negatively correlated with age, systolic blood pressure, diastolic blood pressure, visceral fat area (VFA), and leptin level (r = .47, P<.01; r = .39, P<.01; r = .31, P = .03; r = .47, P<.01; and r = .30, P = .03, respectively). Multiple stepwise regression found that age and VFA were independently associated with PWV (beta = .40, P<.01; beta = .30, P = .02, respectively). PWV, body mass index, VFA, and metabolic profiles all improved significantly 12 months after RYGB. The change in PWV was positively correlated with changes in VFA and the leptin level (r = .40, P = .03; r = .40, P = .02, respectively). CONCLUSIONS: Decreased VFA resulting from RYGB correlated with improved arterial stiffness in obese Chinese patients with T2DM. Leptin might be an important factor linking PWV and visceral fat accumulation. PMID- 26826924 TI - Diverted sleeve gastrectomy with ileal transposition in overweight, obese, and morbidly obese patients with type 2 diabetes: results of 1-year follow-up. AB - BACKGROUND: Bariatric surgery is an effective intervention for morbidly obese individuals, and it normalizes the level of glycemia in the majority of patients with type 2 diabetes mellitus (T2DM). OBJECTIVES: The primary aim of the study was to examine the efficacy of diverted sleeve gastrectomy with ileal transposition on weight loss and glycemic control in overweight, obese, and morbidly obese T2DM patients. The secondary aim was to examine the relationship between the effect of surgery and body mass index (BMI). SETTING: Metabolic surgery clinic. METHODS: This study was performed between October 2011 and August 2014, and mean duration of follow-up was 1 year. A total of 131 patients with T2DM were included. Ileal transposition with sleeve gastrectomy were performed in all patients. Each patient received a standard mixed meal tolerance test; plasma glucose, C-peptide, and insulin concentrations were measured before and 1 hour after the test. Postoperative alterations in BMI were noted. RESULTS: Mean BMI decreased from 33.1+/-.5 to 23.5+/-.2 kg/m(2) at 1 year, with the magnitude of weight loss correlating with baseline weight (P<.0001). There were marked decreases in fasting plasma glucose concentration and mean glycosylated hemoglobin levels at 1 year. Neither the decrease in fasting plasma glucose or glycosylated hemoglobin correlated with the decrease in weight. The homeostasis model assessment index decreased from 9.6+/-1.2 to 2.2+/-.2, P<.0001, and the Matsuda index for insulin sensitivity increased from 2.2+/-.2 to 7.8+/-.4, P<.0001. Despite the improvement in insulin sensitivity, surgery caused a 4-fold increase in insulin secretion (P<.01). CONCLUSION: Diverted sleeve gastrectomy with ileal transposition is effective in glycemic control in patients with T2DM; however, this was not dependent on preoperative BMI values. PMID- 26826925 TI - Vacuum-Assisted Closure in the Management of Degloving Soft Tissue Injury: A Case Report. AB - We report the case of a patient with an extensive degloving injury to his right foot involving severe subcutaneous soft tissue disruption and contamination. The initial treatment consisted of debridement, which was kept to a minimum, copious irrigation, primary wound closure at a few sites, and coverage of the remaining skin defects with vacuum-assisted closure (VAC) dressings. After a few weeks of VAC therapy for wound bed preparation, definitive coverage with a meshed skin graft was possible. Additional plastic surgical procedures were not required. At the last follow-up visit, the patient had no complaints and was able to participate in normal social life without limitations. Wounds that are grossly contaminated or associated with extensive soft tissue defects often require a multistage approach before delayed primary wound closure or plastic surgical procedures can be performed. Vacuum therapy can be used for temporary soft tissue coverage and has been shown to improve bacterial clearance, to increase local blood flow, and to promote granulation tissue formation. In contrast, plastic surgical procedures initially achieve safe and stable wound closure; however, the absence of sensitivity can lead to secondary problems. This is of particular relevance if the graft recipient site is subject to heavy stress and the restoration of function is of paramount importance, such as in the present case. Vacuum therapy is an effective and safe treatment of degloving injuries. We achieved a very good functional outcome, which was particularly important in view of the high stresses and strains to which a foot is exposed. PMID- 26826926 TI - Generation and validation of PAX7 reporter lines from human iPS cells using CRISPR/Cas9 technology. AB - Directed differentiation of iPS cells toward various tissue progenitors has been the focus of recent research. Therefore, generation of tissue-specific reporter iPS cell lines provides better understanding of developmental stages in iPS cells. This technical report describes an efficient strategy for generation and validation of knock-in reporter lines in human iPS cells using the Cas9-nickase system. Here, we have generated a knock-in human iPS cell line for the early myogenic lineage specification gene of PAX7. By introduction of site-specific double-stranded breaks (DSB) in the genomic locus of PAX7 using CRISPR/Cas9 nickase pairs, a 2A-GFP reporter with selection markers has been incorporated before the stop codon of the PAX7 gene at the last exon. After positive and negative selection, single cell-derived human iPS clones have been isolated and sequenced for in-frame positioning of the reporter construct. Finally, by using a nuclease-dead Cas9 activator (dCas9-VP160) system, the promoter region of PAX7 has been targeted for transient gene induction to validate the GFP reporter activity. This was confirmed by flow cytometry analysis and immunostaining for PAX7 and GFP. This technical report provides a practical guideline for generation and validation of knock-in reporters using CRISPR/Cas9 system. PMID- 26826927 TI - Conversion of adult human peripheral blood mononuclear cells into induced neural stem cell by using episomal vectors. AB - Human neural stem cells (NSCs) hold great promise for research and therapy in neural diseases. Many studies have shown direct induction of NSCs from human fibroblasts, which require an invasive skin biopsy and a prolonged period of expansion in cell culture prior to use. Peripheral blood (PB) is routinely used in medical diagnoses, and represents a noninvasive and easily accessible source of cells. Here we show direct derivation of NSCs from adult human PB mononuclear cells (PB-MNCs) by employing episomal vectors for transgene delivery. These induced NSCs (iNSCs) can expand more than 60 passages, can exhibit NSC morphology, gene expression, differentiation potential, and self-renewing capability and can give rise to multiple functional neural subtypes and glial cells in vitro. Furthermore, the iNSCs carry a specific regional identity and have electrophysiological activity upon differentiation. Our findings provide an easily accessible approach for generating human iNSCs which will facilitate disease modeling, drug screening, and possibly regenerative medicine. PMID- 26826928 TI - Chyle leak following right axillary lymph node dissection: A case report and review of current literature. AB - This report discusses the case of a chyle leak following a right axillary lymph node dissection for breast cancer. This presented as a sudden change in drainage character from a right axillary surgical drain from serous to milky white shortly after restarting a diet. The diagnosis of chyle leak was confirmed by laboratory testing of the fluid and managed with closed suction drainage. Chyle leak is a rare, but increasingly recognized complication following axillary clearance for breast cancer and melanoma. PMID- 26826929 TI - Seat belt syndrome: Delayed or missed intestinal injuries, a case report and review of literature. AB - INTRODUCTION: Seat belt injuries are not uncommon. The use of seat belts is associated with a unique injury profile collectively termed "the seat belt syndrome". The aim is to aid in the early diagnosis of seat belt injuries. CASE PRESENTATION: Two different patients presented to the emergency after sustaining a motor vehicle accident. Both were the drivers, restrained and had a frontal impact. On presentation they were hemodynamically stable with mild tenderness on the abdomen and the abdominal computed tomography (CT) did not show any signs of bowel or mesenteric injuries. The signs of peritonitis became obvious after 24h in one case and after 3 days in the other. DISCUSSION: Early diagnosis provides better outcomes for patients with seat belt injuries, but this remains a challenge to trauma surgeons. The typical findings of peritonitis might not be present initially. The presence of abdominal wall ecchymosis (seat belt sign) increases the chance of intraabdominal injuries by eight folds. CONCLUSION: Clinical signs of intestinal injuries might not be obvious on presentation. In the presence of seat belt sign the possibility of bowl injury must be suspected. Admit the patient for observation even if no clinical or radiological findings are present at presentation. PMID- 26826930 TI - Retrograde flexible ureteroscopy-assisted retroperitoneal laparoscopic ureteroureterostomy for refractory ureteral stricture: A case report. AB - INTRODUCTION: Laparoscopic ureteroureterostomy (UU) is a preferred and valid minimally invasive procedure for treatment of benign ureteral strictures. In some cases with chronic inflammation or after repeated endoscopic ureteral surgery, it is difficult to identify the location of a ureteral stricture. PRESENTATION OF CASE: We report a case of 48-year-old man with an impacted stone after laparoscopic partial nephrectomy. Although transurethral lithotripsy (TUL) was performed, the ureteral stricture did not improve by subsequent endoscopic ureteral Holmium laser incision and balloon dilation. DISCUSSION: To simultaneously identify the exact location of the constriction, we performed retroperitoneal laparoscopic ureteroureterostomy with intraoperative observations via super-slim flexible fiberoptic ureteroscopy retrograde. CONCLUSIONS: Accurate identification of the ureteral stricture via observation by laparoscopy and observation by ureteroscopy was feasible. In contrast to the use of a rigid ureteroscopy, flexible fiberoptic ureteroscopy did not require placing the patient in an unnatural position. PMID- 26826931 TI - Hepatoblastoma of the adult with pericardial metastasis: A case report. AB - BACKGROUND: Hepatoblastoma is the most frequent liver tumor in children, but very rare in the adult and associated with an unfavorable prognosis. The diagnosis is always postoperative or post mortem and biopsy is not useful. Surgery is the only accepted treatment. CASE PRESENTATION: Our patient underwent surgery in the suspect of liver metastasis from a previous gastric cancer. Surgery consisted in left lobectomy with partial diaphragm resection and partial pericardiectomy for a pericardial lesion, found after the opening of the thorax. The diaphragm defect was corrected with a biological mesh. RESULTS: The histopathological examination indicated hepatoblastoma of the adult with pericardial metastases. The patient was asymptomatic and without recurrence after 21 months of follow up. CONCLUSION: The hepatoblastoma of the adult is related to a poor prognosis with median survival time less than 5 months. Surgery is the only curative treatment, but in many cases tumor resection requires complex operations. Vascular and thoracic expertise could be useful in the management of hepatoblastoma. PMID- 26826932 TI - Case report of nodular melanoma within congenital melanocytic nevus- primary closure challenge. AB - INTRODUCTION: Congenital melanocytic nevi (CMN) are present in 1-2% of newborn infants. The size of CMN defines the risk of developing melanoma which is estimated from 5-10%, especially in lesions that are located across the spine. PRESENTATION OF CASE: Herein we report a case where nodular melanoma was discovered on the periphery of medium sized CMN in a high risk patient. After complete excision, the defect was reconstructed with random pattern, triple rhomboid flap. DISCUSSION: Melanoma that arose within medium sized CMN would leave a complex posterior lower trunk defect. We used a triple Limberg flap which was proven to be straightforward and simple method when large defects are to be covered with vital tissue. We have also showed that this type of reconstruction is suitable for high risk patients that could not withstand any complex procedures. CONCLUSION: In our case, the method we choose to reconstruct the defect proved to be simple, safe and easy, especially when surgery is performed in a high risk patient. PMID- 26826933 TI - Laparoscopic treatment of acute small bowel obstruction due to left paraduodenal hernia: A case report and literature review. AB - INTRODUCTION: Internal hernia is a pathological condition resulting from abnormal protrusion of abdominal viscera through an opening in the intraperitoneal recesses of the abdominal cavity. Small bowel obstruction due to internal hernia is not common (0.25-0.9% of cases). The most common group is that of paraduodenal hernias (53%), of which the left-sided one is the most common type (75%). PRESENTATION OF CASE: We report a case of a 43 year-old man with a history of recurrent abdominal pain, who was hospitalized because of an episode of acute small bowel obstruction. He had no previous surgery. Computed tomography revealed an encapsulated circumscribed cluster of jejunal loops in the left upper quadrant, near the ligament of Treitz, and the hernia orifice was adjacent to the left side of the inferior mesenteric vessels. Emergency laparoscopic surgery was performed: the small bowel was found completely herniated under the inferior mesenteric vessels. It was gradually reduced and the hernia space was closed with a running suture. The patient was discharged on the fourth day without complications. CONCLUSION: Left paraduodenal hernia is a rare cause of small bowel obstruction that should be taken into account in a patient with a history of recurrent abdominal pain or intestinal obstruction, and no previous surgery. Computed tomography is the standard for a correct diagnosis. Surgery is treatment of choice, because it reduces the risk of emergency and complications associated to hernia. Laparoscopic approach is feasible and effective, also in emergency situation. PMID- 26826934 TI - Wernicke's encephalopathy after sleeve gastrectomy: Literature review. AB - OBJECTIVE: To describe a case of Wernicke's encephalopathy after laparoscopic sleeve gastrectomy. SETTING: Emergency Department and gastrointestinal surgery department. CASE REPORT: A 20-year-old man class III obesity (BMI 50.17kg/m(2)) underwent laparoscopic sleeve gastrectomy with uneventful recovery. Five weeks after surgery he was admitted in the Emergency Department because of persistent vomiting and dysphagia to solids. Esophagogastroduodenal transit and upper gastrointestinal endoscopy were requested but no relevant findings were shown. Laboratory analyses showed vitamin B1 12.2ng/mL and 48h following admission the patient experienced generalized weakness, sialorrhea and restrictions of actions such as reading a book. Neurological evaluation found confusion, motor ataxia, diplopy and nystagmus. A brain magnetic resonance was normal. According to low level of vitamin B1 and symptoms found in the patient a presumed diagnosis of Wernicke encephalopathy was made and parenteral thiamine 100mg/day was started. The patient was discharged asymptomatic with oral intake of vitamin B1 600mg per day. CONCLUSION: Nutritional deficiencies after restrictive procedures are uncommon but easily preventable and can result in life threatening. With the upswing of bariatric surgery, surgeons and emergency physicians should be able to diagnose and treat those complications. Prophylactic thiamine should be administered to patients with predisposing factors. PMID- 26826935 TI - Inflammatory pseudotumor of the liver occurring during the course of hepatitis C virus-related hepatocellular carcinoma treatment: A case report. AB - INTRODUCTION: Inflammatory pseudotumor (IPT) of the liver is a rare and benign disease that has a good prognosis. It is often difficult to distinguish IPT from hepatic malignancies, such as hepatocellular carcinoma (HCC), because specific clinical symptoms are absent and the diseases' radiological findings can be similar. IPT is particularly difficult to distinguish from HCC in livers with hepatitis C virus (HCV)-related cirrhosis. We report a case of IPT of the liver that mimicked HCV-related HCC recurrence. PRESENTATION OF CASE: A 78-year-old asymptomatic Japanese man who had undergone hepatectomy for HCV-related HCCs (moderately differentiated type) in segments 7 and 5 four and a half years previously was referred to our hospital for treatment of a 30-mm enhanced tumor in segment 5 (a typical HCC pattern). The tumor was identified via abdominal dynamic computed tomography (CT) and CT with hepatic arteriography and arterial portography. Thereafter, liver segmentectomy 5 was performed, and the histopathological diagnosis was a 10-mm IPT of the liver. After 1.5 years, magnetic resonance imaging revealed two new enhanced lesions in segment 8, which showed the typical pattern of HCC. Because these lesions grew in size for 3 months, liver segmentectomy 8 was performed for HCC recurrence. Histopathological examination showed that both lesions were HCCs. CONCLUSION: HCV-related HCC has a high rate of multicentric recurrence. Our experience suggests that, when a hepatic lesion is suspected to be HCC, surgical resection should be considered for curative treatment and to rule out malignancy, even if the lesion may be an IPT. PMID- 26826936 TI - Transsacral rectocele following combined neurinoma resection: A case report. AB - INTRODUCTION: This report describes for the first time a case of a transsacral rectocele after combined abdominotranssacral tumour resection. Furthermore, we demonstrate a method for laparoscopic defect repair. PRESENTATION OF CASE: A 44 year-old Caucasian female presented to our hospital with strange gurgling sounds and a painless subdermal swelling in her lower back after resection of a presacral neurinoma two years earlier. Magnetic resonance imaging (MRI) showed a huge rectocele through a sacral defect extending into the subcutaneous tissue. We performed a laparoscopic defect repair with the implantation of a self-fixating mesh graft. Five days after surgery, the patient was discharged in a good general condition. Five months after the operation, a follow-up MRI showed a good postoperative result with the correct position of the rectum. DISCUSSION: The repair of transsacral prolapses with attachment of a mesh is complicated by the high rigidity of the pelvis and its surrounding structures. The key criteria in choosing the method of operative approach are the size and content of the prolapse. Huge sacral defects with bowel prolapses require a transabdominal approach to enable repositioning the bowel into the abdomen and excluding bowel injuries and inner hernias. CONCLUSION: A laparoscopic approach provides a good intraoperative visibility for a safe retrorectal preparation and mesh graft repair of sacral defects. PMID- 26826937 TI - Implantation depth measured by 64-slice computed tomography is associated with permanent pacemaker requirement following transcatheter aortic valve implantation with the Core Valve((r)) system. AB - BACKGROUND: Patients undergoing transcatheter aortic valve implantation (TAVI) are at increased risk for post-interventional conduction disturbances leading to pacemaker (PM) implantation. We analyzed the association between implantation depth within the left ventricular outflow tract (LVOT), measured by 64-slice computed tomography (CT), and 'index electrocardiographic (ECG) changes' (new onset atrioventricular-block grade II or III or left bundle branch block with PR interval prolongation >200ms). METHODS: We evaluated patients who underwent TAVI with the Core Valve((r)) revalving system (Medtronic, Minneapolis, MN, USA) for treatment of severe aortic stenosis at our department. Patients with a prior PM implantation and patients for whom no CT scan was available after 3 months were excluded from analysis. We assessed implantation depth of the prosthesis within the LVOT as possible risk factors for the development of post-interventional 'index ECG changes' resulting in PM implantation and compared it with individual patient data as well as echocardiographic and electrocardiographic parameters. RESULTS: The final study cohort comprised 53 patients for whom a 64-slice CT scan was available (mean age 81.7+/-5.1 years, 36% male). Twenty-eight of these finally underwent PM implantation due to 'index ECG changes' within the first 48hours after TAVI. Univariate logistic regression analysis could identify implantation depth of the prosthesis as the only significantly correlated risk factor for PM need in our cohort (OR 1.27, 95% CI: 1.08-1.51, p=0.004). A cut-off value of 6mm predicted this need with a sensitivity of 89% and specificity of 40%. CONCLUSION: Implantation depth of the Core Valve((r)) into the LVOT was associated with post-procedural PM requirement. Thereby, a cut-off value of 6mm, as measured by 64-slice CT, proved useful to define patients at risk for PM requirement. PMID- 26826938 TI - Simultaneous removal and degradation characteristics of sulfonamide, tetracycline, and quinolone antibiotics by laccase-mediated oxidation coupled with soil adsorption. AB - The uses of laccase in the degradation and removal of antibiotics have recently been reported because of the high efficiency and environmental friendliness of laccase. However, these removal studies mostly refer to a limited number of antibiotics. In this study, soil adsorption was introduced into the laccase oxidation system to assist the simultaneous removal of 14 kinds of sulfonamide, tetracycline, and quinolone antibiotics, which differed in structures and chemical properties. The complementary effects of laccase-mediated oxidation and soil adsorption enabled the simultaneous removal. Removal characteristics were determined by a comprehensive consideration of the separate optimum conditions for laccase oxidation and soil adsorption removal experiments. With concentrations of laccase, syringaldehyde (SA), and soil of 0.5mg/mL, 0.5mmol/L, and 50g/L, respectively, and at pH 6 and 25 degrees C, the removal rates of each antibiotic exceeded 70% in 15min and were close to 100% in 180min. Sulfonamide antibiotics (SAs) were removed mainly by laccase oxidation and quinolone antibiotics (QUs) mainly by soil adsorption. Tetracycline antibiotics (TCs) were removed by both treatments in the coupled system, but laccase oxidation dominated. Electrostatic adsorption was speculated to be one of the adsorption mechanisms in soil adsorption with QUs and TCs. PMID- 26826939 TI - Novel approach for predicting the joint effects based on the enzyme-catalyzed kinetics. AB - Organisms are exposed to mixtures of multiple contaminants and it is necessary to build prediction models for the joint effects, considering the high expense and the complexity of the traditional toxicity testing and the flood occurrence of environmental chemical pollutants. In this study, a new method for predicting the joint effects was developed and corresponding prediction models were constructed based on the kinetic models of enzyme-catalyzed reactions. While, we utilized Vibrio fischeri, Escherichia coli and Bacillus subtilis as model organisms and determined the chronic toxicity of the binary mixtures of sulfonamides (SAs) and sulfonamide potentiators (SAPs) (SA+SAP), the mixtures of two kinds of sulfonamides (SA+SA) and the binary mixtures of sulfonamide potentiators (SAPs) and tetracyclines (TCs) (SAP+TC) respectively. Finally, corresponding mixture toxicity data was utilized to fit and verify the prediction models for different joint effects. PMID- 26826940 TI - Cognitive and numerosity predictors of mathematical skills in middle school. AB - There is a strong research base on the underlying concomitants of early developing math skills. Fewer studies have focused on later developing skills. Here, we focused on direct and indirect contributions of cognitive measures (e.g., language, spatial skills, working memory) and numerosity measures, as well as arithmetic proficiency, on key outcomes of fraction performance, proportional reasoning, and broad mathematics achievement at sixth grade (N=162) via path analysis. We expected a hierarchy of skill development, with predominantly indirect effects of cognitive factors via number and arithmetic. Results controlling for age showed that the combination of cognitive, number, and arithmetic variables cumulatively accounted for 38% to 44% of the variance in fractions, proportional reasoning, and broad mathematics. There was consistency across outcomes, with more proximal skills providing direct effects and with the effects of cognitive skills being mediated by number and by more proximal skills. Results support a hierarchical progression from domain-general cognitive processes through numerosity and arithmetic skills to proportional reasoning to broad mathematics achievement. PMID- 26826941 TI - Retrospective Review of 516 Implantations of Option Inferior Vena Cava Filters at a Single Health Care System. AB - PURPOSE: To retrospectively evaluate the safety, efficacy, and retrievability of Option inferior vena cava (IVC) filters. MATERIALS AND METHODS: All patients (N = 516; 247 women; mean age, 67.1 y +/- 15.1; range, 19.5-101.6 y) who received an Option filter between August 2009 and March 2015 at a single health care system were analyzed. RESULTS: The study duration was 68 months, with median clinical follow-up of 7.1 months (range, 1 d to 61.8 mo). During follow-up, 73 of 83 patients (88.0%) underwent successful filter retrieval, 153 died (including three after successful retrieval), and 293 remained alive with filters in situ. Seventeen cases of breakthrough pulmonary embolism (PE) occurred (3.4%). Among 323 patients with direct filter imaging, there were two cases of tilt > 15 degrees , one case of filter deformity, 16 cases of intracaval migration > 2 cm, and no cases of filter fracture. There were six cases of caval occlusion, nine cases of thrombus trapped inside the filter, and 57 cases of limb penetration on computed tomography scans or radiographs of the IVC. Retrieval failures were attributed to filter tilt or tip embedment in the caval wall (n = 4), complete IVC thrombosis (n = 3), thrombus inside the filter (n = 2), or inability to disengage filter legs (n = 1). Recurrent deep vein thrombosis occurred in 34 patients, including 32 with filters in situ and two whose filters had been removed. CONCLUSIONS: Most Option filters were left in situ for permanent indications. Rates of successful retrieval, device-related complications, and breakthrough PE were similar to those associated with other retrievable filters. PMID- 26826942 TI - [Assessment of negative stereotypes about old age in young people and adults]. AB - INTRODUCTION: Negative stereotypes towards ageing and the old age may negatively influence relationships and working with older people. The CENVE (Negative Stereotypes Towards Ageing) questionnaire is a validated Spanish tool designed to evaluate these stereotypes, but there are no evidence about its factorial structure with young people and adults. This factorial structure of CENVE is analysed in non-elderly subjects, and its relationship with various sociodemographic and experience-related indicators is also examined. METHOD: A total of 350 young people and adults completed the CENVE. Information on demographics, specialised academic training in aging, and level of contact with elderly people were also provided. An analysis was performed on the factorial structure of the questionnaire and its relationship with socio-demographic and experiential indicators. RESULTS: The analyses performed did not confirm the original structure in 3 sub-scales, suggesting an alternative one-dimensional structure. It also suggested the existence of different ageist stereotypes associated with the socio-demographic profile of non-elderly subjects (particularly related to educational level). Less conclusive results were obtained regarding former experience and level of information on aging. CONCLUSIONS: CENVE is a useful tool for evaluating ageism, but in the present article a one-dimensional correction is suggested for the non-elderly population. PMID- 26826943 TI - Detailed evaluation of the upper urinary tract in patients with prune belly syndrome using magnetic resonance urography. AB - INTRODUCTION: Magnetic resonance urography (MRU) has proven to be useful in the setting of complex urologic anatomy. Prune belly syndrome (PBS) patients are known to have malformed and highly variable urinary tract anatomy due to significant dilation and renal dysplasia. OBJECTIVE: To further characterize the renal and ureteral anatomy and renal function in patients with PBS via MRU. STUDY DESIGN: Children with PBS undergoing MRU (2006-2011) were identified. Studies were performed to evaluate severe hydronephrosis in all patients. Demographics, previous imaging, and MRU findings were collected. A single radiologist reviewed all studies. RESULTS: MRU was performed on 13 boys, with a median age of 29.3 months (IQR 6-97). Two patients underwent >1 study for ureteropelvic junction obstruction (UPJ obstruction) and calyceal diverticulum with a solitary kidney, respectively. Hydroureteronephrosis (HUN) was identified in 12 boys (92%), while one (8%) did not have ureteral dilation. All patients demonstrated morphologic abnormalities beyond HUN as follows: five (38%) renal dysplasia; five (38%) scarring; four (31%) calyceal diverticula; and three (23%) thickened bladder. The median renal transit time (RTT) was 6 min (IQR 3.5-10.5), and >8 min (range 8.5 35) in six patients; one patient was ultimately diagnosed with obstruction. The mean serum creatinine was 0.5 +/- 0.3 mg/dl. This summary figure is a coronal excretory phase T1 MRU image demonstrating absence of well-defined calyces and a 5-cm calyceal diverticulum (white arrow). DISCUSSION: This study reports significant anatomic and functional findings on MRU that were not readily apparent when using standard imaging for children with PBS. The high-resolution images and functional data obtained with MRU allowed for visualization of calyceal diverticula and abnormal renal pelvic anatomy not previously described in PBS. In addition, renal dysplasia could be identified with MRU, which is badly characterized in the PBS population outside of renal biopsy studies. Potential limitations of the study included its nature as a small retrospective case series, which limited the ability to compare imaging modalities. Imaging modalities were based on individual clinical needs; therefore, comparison with diuretic renal scintigraphy was limited. CONCLUSION: MRU provided anatomic and functional details of the urinary tract in children with PBS that allowed for characterization of new renal anatomic abnormalities, including the incidence of calyceal diverticula and renal dysplasia, which have not been previously described. While renal scarring, dysplasia and calyceal diverticula were easily discerned on MRU in ten patients, their clinical significance requires longer follow-up in a larger patient population. PMID- 26826944 TI - Renal function tests also exist. PMID- 26826945 TI - Prosthetic alignment after total knee replacement is not associated with dissatisfaction or change in Oxford Knee Score: A multivariable regression analysis. AB - BACKGROUND: Approximately 18% of the patients are dissatisfied with the result of total knee replacement. However, the relation between dissatisfaction and prosthetic alignment has not been investigated before. METHODS: We retrospectively analysed prospectively gathered data of all patients who had a primary TKR, preoperative and one-year postoperative Oxford Knee Scores (OKS) and postoperative computed tomography (CT). The CT protocol measures hip-knee-ankle (HKA) angle, and coronal, sagittal and axial component alignment. Satisfaction was defined using a five-item Likert scale. We dichotomised dissatisfaction by combining '(very) dissatisfied' and 'neutral/not sure'. Associations with dissatisfaction and change in OKS were calculated using multivariable logistic and linear regression models. RESULTS: 230 TKRs were implanted in 105 men and 106 women. At one year, 12% were (very) dissatisfied and 10% neutral. Coronal alignment of the femoral component was 0.5 degrees more accurate in patients who were satisfied at one year. The other alignment measurements were not different between satisfied and dissatisfied patients. All radiographic measurements had a P-value>0.10 on univariate analyses. At one year, dissatisfaction was associated with the three-months OKS. Change in OKS was associated with three-months OKS, preoperative physical SF-12, preoperative pain and cruciate retaining design. DISCUSSION: Neither mechanical axis, nor component alignment, is associated with dissatisfaction at one year following TKR. Patients get the best outcome when pain reduction and function improvement are optimal during the first three months and when the indication to embark on surgery is based on physical limitations rather than on a high pain score. LEVEL OF EVIDENCE: 2. PMID- 26826946 TI - Gel-type autologous chondrocyte implantation for cartilage repair in patients with prior ACL reconstruction: A retrospective two year follow-up. AB - PURPOSE: To describe the early patient-reported outcomes of articular cartilage repair in patients with pain due to grade III or IV articular cartilage defects after prior anterior cruciate ligament (ACL) reconstruction. METHODS: Nineteen patients underwent a gel-type autologous chondrocyte implantation (GACI) procedure after ACL reconstruction. Median timeframe between ACL reconstruction and GACI procedure was 52 months (range 16 to 369). The average age at chondrocyte implantation was 35 (standard deviation (SD) eight) years and average cumulative articular cartilage defect size was nine (SD four) square centimeter. Outcome was assessed prior to the GACI procedure and two years after GACI using the International Knee Documentation Committee (IKDC) score and the Knee injury and Osteoarthritis Outcome Score (KOOS). RESULTS: Two year post-GACI scores showed a statistically significant improvement of IKDC (13, SD 22, p=.02) and KOOS quality of life (18, SD 27, p=.01) compared to the pre-GACI scores. The other KOOS domains did improve, but not statistically significant. Seven (37%) patients underwent reoperation after the GACI. CONCLUSION: Patients with prior ACL reconstruction and suffering from ongoing pain associated with cartilage defects can benefit from cartilage repair with GACI. PMID- 26826948 TI - Studying small brains to understand the building blocks of cognition. AB - Cognition encompasses a range of higher-order mental processes, such as attention, working memory, and model-based decision-making. These processes are thought to involve the dynamic interaction of multiple central brain regions. A mechanistic understanding of such computations requires not only monitoring and manipulating specific neural populations during behavior, but also knowing the connectivity of the underlying circuitry. These goals are experimentally challenging in mammals, but are feasible in numerically simpler insect brains. In Drosophila melanogaster in particular, genetic tools enable precisely targeted physiology and optogenetics in actively behaving animals. In this article we discuss how these advantages are increasingly being leveraged to study abstract neural representations and sensorimotor computations that may be relevant for cognition in both insects and mammals. PMID- 26826949 TI - Exploring revictimization process among Turkish women: The role of early maladaptive schemas on the link between child abuse and partner violence. AB - The purpose of the current study is to explore the revictimization process between child abuse and neglect (CAN), and intimate partner violence (IPV) based on the schema theory perspective. For this aim, 222 married women recruited in four central cities of Turkey participated in the study. Results indicated that early negative CAN experiences increased the risk of being exposed to later IPV. Specifically, emotional abuse and sexual abuse in the childhood predicted the four subtypes of IPV, which are physical, psychological, and sexual violence, and injury, while physical abuse only associated with physical violence. To explore the mediational role of early maladaptive schemas (EMSs) on this association, first, five schema domains were tested via Parallel Multiple Mediation Model. Results indicated that only Disconnection/Rejection (D/R) schema domains mediated the association between CAN and IPV. Second, to determine the particular mediational roles of each schema, eighteen EMS were tested as mediators, and results showed that Emotional Deprivation Schema and Vulnerability to Harm or Illness Schema mediated the association between CAN and IPV. These findings provided an empirical support for the crucial roles of EMSs on the effect of revictimization process. Clinical implications were discussed. PMID- 26826947 TI - Interobserver Agreement of the Eaton-Glickel Classification for Trapeziometacarpal and Scaphotrapezial Arthrosis. AB - PURPOSE: To determine whether simplification of the Eaton-Glickel (E-G) classification of trapeziometacarpal (TMC) joint arthrosis (eliminating evaluation of the scaphotrapezial [ST] joint) and information about the patient's symptoms and examination influence interobserver reliability. We also tested the null hypotheses that no patient and/or surgeon factors affect radiographic rating of TMC joint arthrosis and that no surgeon factors affect the radiographic rating of ST joint arthrosis. METHODS: In an on-line survey, 92 hand surgeons rated TMC joint arthrosis and ST joint arthrosis separately on 30 radiographs (Robert, true lateral, and oblique views) according to the (modified) E-G classification. We randomly assigned 42 observers to review radiographs alone and also informed 50 of the patient's symptoms and examination. Information about symptoms and examination was randomized. Interobserver reliability was determined with the s* statistic. Because of the hierarchical data structure, cross-classified ordinal multilevel regression analyses were performed to identify factors associated with the severity of arthrosis. RESULTS: Shortening the E-G classification to the first 3 stages significantly improved the interobserver reliability, which approached substantial agreement. Providing clinical information to observers marginally improved interobserver reliability. Factors associated with a lower E G stage for TMC joint arthrosis, among observers who rated the severity of TMC joint arthrosis based on radiographs and clinical information, included female surgeon, practice setting, supervising surgical trainees in the operating room, self-reported number of patients with TMC joint arthrosis typically treated annually, male patient, higher patient age, pain limiting daily activities, and shoulder sign. A self-reported larger number of patients with TMC joint arthrosis treated annually was the only variable associated with a higher modified E-G classification to rate ST joint arthrosis. CONCLUSIONS: Our findings suggest that simpler classifications that focus on a single anatomical area are reliable and that surgeon and patient factors can bias interpretation of objective pathophysiology such as radiographic findings. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III. PMID- 26826950 TI - Immune-surveillance through exhausted effector T-cells. AB - Pathogens such as the human immunodeficiency virus (HIV), the hepatitis B and C virus (HBV, HCV) and certain strains of the rodent lymphocytic choriomeningitis virus (LCMV) establish a state of persisting viral replication. This occurs besides strong adoptive immune responses and the induction of large numbers of activated pathogen-specific T-cells. The failure of the immune system to clear these viruses is typically attributed to a loss of effector T-cell function-a phenomenon referred to as T-cell exhaustion. Though largely accepted, this loss of function concept is being more and more challenged by comprehensive clinical and experimental observations which highlight that T-cells in chronic infections are more functional than previously considered. Here, we highlight examples that demonstrate that such T-cells mediate a profound form of immune-surveillance. We also briefly discuss the opportunities and limitations of employing 'exhausted' T cells for therapeutic purposes. PMID- 26826951 TI - Cross host transmission in the emergence of MERS coronavirus. AB - Coronaviruses (CoVs) able to infect humans emerge through cross-host transmission from animals. There is substantial evidence that the recent Middle East respiratory syndrome (MERS)-CoV outbreak is fueled by zoonotic transmission from dromedary camels. This is largely based on the fact that closely related viruses have been isolated from this but not any other animal species. Given the widespread geographical distribution of dromedaries found seropositive for MERS CoV, continued transmission may likely occur in the future. Therefore, a further understanding of the cross host transmission of MERS-CoV is needed to limit the risks this virus poses to man. PMID- 26826952 TI - Perspectives on recycling centres and future developments. AB - The overall aim of this paper is to draw combined, all-embracing conclusions based on a long-term multidisciplinary research programme on recycling centres in Sweden, focussing on working conditions, environment and system performance. A second aim is to give recommendations for their development of new and existing recycling centres and to discuss implications for the future design and organisation. Several opportunities for improvement of recycling centres were identified, such as design, layout, ease with which users could sort their waste, the work environment, conflicting needs and goals within the industry, and industrialisation. Combining all results from the research, which consisted of different disciplinary aspects, made it possible to analyse and elucidate their interrelations. Waste sorting quality was recognized as the most prominent improvement field in the recycling centre system. The research identified the importance of involving stakeholders with different perspectives when planning a recycling centre in order to get functionality and high performance. Practical proposals of how to plan and build recycling centres are given in a detailed checklist. PMID- 26826953 TI - Periodic peristalsis releasing constrained water in high solids enzymatic hydrolysis of steam exploded corn stover. AB - Periodic peristalsis was used to release water constraint and increase high solids enzymatic hydrolysis efficiency. Glucan and xylan conversion in periodic peristalsis enzymatic hydrolysis (PPEH) at 21% solid loading increased by 5.2 6.4% and 6.8-8.8% compared with that in incubator shaker enzymatic hydrolysis (ISEH), respectively. Hydrolysis kinetics suggested that sugars conversion significantly increased within 24h in PPEH compared with ISEH. The peak height of main water pool increased by 7.7-43.1% within 24h in PPEH compared with ISEH. The increases in peak height of main water pool were consistent with the increases in glucan conversion. Submicroscopic particulates and macro granule residues contributed greatly to water constraint compared with glucose, xylose, ethanol, and Tween 80. Smaller particle size and longer residence time resulted in lower water constraint and facilitated the enzymatic hydrolysis performance. Periodic peristalsis was an effective method to reduce water constraint and increase high solids enzymatic hydrolysis efficiency. PMID- 26826954 TI - Accounting for all sugars produced during integrated production of ethanol from lignocellulosic biomass. AB - Accurate mass balance and conversion data from integrated operation is needed to fully elucidate the economics of biofuel production processes. This study explored integrated conversion of corn stover to ethanol and highlights techniques for accurate yield calculations. Acid pretreated corn stover (PCS) produced in a pilot-scale reactor was enzymatically hydrolyzed and the resulting sugars were fermented to ethanol by the glucose-xylose fermenting bacteria, Zymomonas mobilis 8b. The calculations presented here account for high solids operation and oligomeric sugars produced during pretreatment, enzymatic hydrolysis, and fermentation, which, if not accounted for, leads to overestimating ethanol yields. The calculations are illustrated for enzymatic hydrolysis and fermentation of PCS at 17.5% and 20.0% total solids achieving 80.1% and 77.9% conversion of cellulose and xylan to ethanol and ethanol titers of 63g/L and 69g/L, respectively. These procedures will be employed in the future and the resulting information used for techno-economic analysis. PMID- 26826955 TI - Mechanical fragmentation of corncob at different plant scales: Impact and mechanism on microstructure features and enzymatic hydrolysis. AB - In this work, corncob samples at different scales, i.e., plant scale (>1mm), tissue scale (500-100MUm) and cellular scale (50-30MUm), were produced to investigate the impact and mechanisms of different mechanical fragmentations on microstructure features and enzymatic hydrolysis. The results showed that the microstructure features and enzymatic hydrolysis of corncob samples, either at a plant scale or tissue scale, did not change significantly. Conversely, corncob samples at a cellular scale exhibited some special properties, i.e., an increase in the special surface area with the inner mesopores and macropores exposed to the surface; breakage of crystalline cellulose and linkages in polysaccharides; and a higher proportion of polysaccharides on the surface, which significantly enhanced enzymatic digestibility resulting in a 98.3% conversion yield of cellulose to glucose which is the highest conversion ever reported. In conclusion, mechanical fragmentation at the cellular scale is an effective pretreatment for corncob. PMID- 26826956 TI - Microbial population dynamics in response to bioaugmentation in a constructed wetland system under 10 degrees C. AB - Compound microbial inocula were enriched and applied to a pilot-scale constructed wetland system to investigate their bioaugmentation effect on nitrogen removal under cold temperature (10 degrees C). The results showed a 10% higher removal efficiency of ammonia and total nitrogen compared to a control (unbioaugmented) group. The microbial community structures before and after the bioaugmentation were analyzed through high throughput sequencing using Miseq Illumina platform. A variation of species richness and community equitability was observed in both systems. It is demonstrated that, based on the response of both the performance and microbial community, bioaugmentation using compound microbial inocula can fine tune the bacterial population and enhance the nitrogen removal efficiency of a constructed wetland system. PMID- 26826957 TI - Effect of hydraulic loading rate on pollutant removal efficiency in subsurface infiltration system under intermittent operation and micro-power aeration. AB - The low hydraulic loading rate (HLR) greatly restricts the wide application of subsurface wastewater infiltration system (SWIS) in densely populated areas. To increase the HLR, an innovative SWIS was developed using cyclic operation mode. In each cycle, a wastewater feeding period is followed by a drying period, in which the aeration is conducted by a medium-pressure fan. Results indicated that the removal rate of TOC and NH4(+)-N were more than 85% at HLR of 0.5m(3)/m(2)d, whereas the TN removal rate was lower than 20%, indicating that the aeration was efficient and denitrification process was largely limited in the SWIS. When HLR decreased from 0.5 to 0.2m(3)/m(2)d, the pollutant removal efficiency enhanced slightly except for TN. Overall, the intermittent operation and micro-power aeration, combined with shunting the pollutant loading were really helpful for SWIS to achieve higher HLR, which offers a reference for the design of innovative SWIS. PMID- 26826958 TI - Biodegradation of carbamazepine using freshwater microalgae Chlamydomonas mexicana and Scenedesmus obliquus and the determination of its metabolic fate. AB - This study evaluated the toxicity and cellular stresses of carbamazepine (CBZ) on Chlamydomonas mexicana and Scenedesmus obliquus, and its biodegradation by both microalgal species. The growth of both microalgal species decreased with increase of CBZ concentration. The growth of S. obliquus was significantly inhibited (97%) at 200 mg CBZ L(-1), as compared to the control after 10days; whereas, C. mexicana showed 30% inhibition at the same experimental conditions. Biochemical characteristics including total chlorophyll, carotenoid contents and enzyme activities (SOD and CAT) for both species were affected by CBZ at relatively high concentration. C. mexicana and S. obliquus could achieve a maximum of 35% and 28% biodegradation of CBZ, respectively. Two metabolites (10,11-dihydro-10,11 expoxycarbamazepine and n-hydroxy-CBZ) were identified by UPLC-MS, as a result of CBZ biodegradation by C. mexicana. This study demonstrated that C. mexicana was more tolerant to CBZ and could be used for treatment of CBZ contaminated wastewater. PMID- 26826959 TI - Performance and microbial community variations in thermophilic anaerobic digesters treating OTC medicated cow manure under different operational conditions. AB - This study aimed to determine the fate and effect of oxytetracycline (OTC) and its metabolites during thermophilic anaerobic digestion of cow manure. OTC medicated and non-medicated digesters were operated at 55 degrees C with different volatile solids (VS) concentrations (4% and 6%) and mixing rates (90 and 120rpm). OTC and its metabolites were measured by HPLC and LC/MS/MS, respectively. Microbial community dynamics were monitored by denaturing gradient gel electrophoresis (DGGE) and real-time PCR (qPCR). Approximately 2mg/L initial OTC concentration caused 10-30% inhibition on biogas production and higher inhibition was observed as mixing rate increased. DGGE results indicated that OTC caused a shift in bacterial community structure and several species became dominant with time. Archaeal community decreased throughout the digestion period. RNA based qPCR analyses showed that gene copy numbers of bacteria and Methanomicrobiales declined in all digesters whereas gene copy numbers of Methanobacteriales and Methanosarcinales increased in high mixing rate digesters. PMID- 26826960 TI - Fuel properties and combustion kinetics of hydrochar prepared by hydrothermal carbonization of bamboo. AB - Hydrothermal carbonization, an environmental friendly treatment method was employed to pretreat bamboo for hydrochar preparation in the present study. Hydrothermal carbonization could elevate the fuel properties and combustion behavior of bamboo. The combustion kinetic parameters of raw bamboo and hydrochars were calculated by a simple Arrhenius equation based on the thermogravimetric curves. Two distinct zones were observed for raw bamboo and hydrochars. The activation energies of raw bamboo in zone 1 and zone 2 were 109.5kJ/mol and 46.6kJ/mol, respectively, in the heating rate of 20 degrees C/min. The activation energy of hydrochar in zone 1 increased at the hydrothermal carbonization temperature under 220 degrees C and then decreased at higher hydrothermal carbonization temperature, due to the decomposition of relative reactive compounds in bamboo, and destruction of cellulose and hemicellulose structures, respectively. The activation energies of hydrochars in zone 2 were among 52.3-57.5kJ/mol, lower than that of lignin extracted from bamboo. PMID- 26826961 TI - Differences in clinical presentation, intraoperative findings and outcome between petroclival and lateral posterior pyramid meningioma. AB - OBJECTIVE: The goal of this study was to determine the impact of the location of the most frequent skull base meningioma of the posterior fossa, i.e. petroclival (PCM) and lateral posterior pyramid meningioma (LPPM) on clinical presentation, surgical treatment and treatment results. PATIENTS AND METHODS: We retrospectively reviewed a consecutive series of patients operated on for PCM (n=46) and LPPM (n=32). Uni- and multivariate analyses were performed to identify differences in clinical presentation, surgical treatment and pre-, intra- and postoperative factors of influence upon the outcome parameters: Complications rate, mortality, tumour recurrence/progress, hospital stay, Karnofsky Performance Score (KPS). RESULTS: At Presentation, the rate of dizziness was higher in LPPM (56% vs. 7%, p<0,001) and trigeminal nerve impairment was more frequent in PCM (50% vs. 3%, p<0,001). Complete tumour resections were more often achieved (91% vs. 39%, p<0,001), and surgery lasted shorter (median: 247 min vs. 500 min, p<0,001) with less blood loss (median: 525 ml vs. 1000 ml, p<0,001) in LPPM compared to PCM. The overall complication rates (73% vs. 31%, p<0,001) as well the rate of irreversible complications (57% vs. 9%, p<0,004) were higher in PCM than in LPPM. The most frequent complications of PCM surgery were eye movement (46% vs. 6%, p<0,001), facial nerve (28% vs. 3%, p<0.02) and swallowing impairments (21% vs. 3%, p<0.02). The perioperative mortality was 11% in PCM and 0% in LPPM patients. In the multivariate analyses, KPS at discharge correlate positively with age (p=0.034) and preoperative KPS (p=0.0048) in LPPM and positively with staged resection (p=0.056) and negatively with the occurrence of surgical complications (p=0,0427) in PCM. Hospitalization time correlated with the blood loss (p<0,001) for PCM, negatively with the preoperative KPS (p=0.0002) for PCM and LPPM and positively with tumour diameter (p=0.0001) and non-surgical complications rate (p=0.0001) for LPPM. CONCLUSION: As compared to LPPM, surgical treatment of PCM is associated with higher morbidity and mortality. The outcome of LPPM was primarily influenced by preoperative factors: Patients age, tumour size, preoperative KPS. The outcome of PCM was primarily influenced by intraoperative factors like: blood loss, surgery duration, staged tumour resection and the surgical complications rate. PMID- 26826962 TI - L-Theanine alleviates the neuropathological changes induced by PCB (Aroclor 1254) via inhibiting upregulation of inflammatory cytokines and oxidative stress in rat brain. AB - The present study is aimed at evaluating the protective role of L-theanine on aroclor 1254-induced oxidative stress in rat brain. Intraperitoneal administration of Aroclor 1254 (2 mg/kg b.wt. for 30 days) caused oxidative stress in rat brain and also caused neurobehavioral changes. Oxidative stress was assessed by determining the levels of lipid peroxide (LPO), protein carbonyl content, and changes in activities of creatine kinase (CK), acetylcholinesterase (AchE), and ATPases in the hippocampus, cerebellum and cerebral cortex of control and experimental rats. Histopathological results showed that PCB caused neuronal loss in all three regions. PCB upregulated the mRNA expressions of inflammatory cytokines. Oral administration of L-theanine (200 mg/kg b.wt.) increased the status of antioxidants, decreased the levels of LPO, nitric oxide (NO) and increased the activities of CK, AchE and ATPases. L-Theanine restored normal architecture of brain regions and downregulated the expression of inflammatory cytokines. In conclusion, L-theanine shows a protective role against PCBs-induced oxidative damage in rat brain. PMID- 26826963 TI - A review on the distribution of Hg in the environment and its human health impacts. AB - Exposure to mercury is a silent threat to the environment and human life. It has the potential to harm almost every organ and body system. Mercury compounds are classified in different chemical types such as elemental, inorganic, and organic forms. The most significant source of ingestion-related mercury exposure in humans and animals is the consumption of fish. Long-term exposure to mercury compounds from different sources (e.g., water, food, soil, and air) can lead to toxic effects on skin, cardiovascular, pulmonary, urinary, gastrointestinal, and neurological systems. Mercury toxicity is found to pose more significant health hazards to certain occupational groups (e.g., goldminers and dental personnel). Because continuous exposure to mercury can be dangerous, it is desirable to re evaluate the current reference (risk-free) values. This paper reviews the route of Hg exposure to humans, its human health impacts, the associated risk assessment, and treatment based on the recent findings from various studies. PMID- 26826964 TI - Self-sustainable Chlorella pyrenoidosa strain NCIM 2738 based photobioreactor for removal of Direct Red-31 dye along with other industrial pollutants to improve the water-quality. AB - The genotoxic and carcinogenic effects of diazo dyes from industrial effluents pose a serious environmental threat by contaminating aquatic ecosystem and consequently impact human health. The potential of a diazo dye resistant, self sustainable photosynthetic green alga Chlorella pyrenoidosa NCIM 2738 provides a viable green technology for an efficient biodegradation of diazo dye Direct Red 31 (DR-31) and overall improvement of water quality. Herein, we for the first time report the degradation of DR-31 using C. pyrenoidosa. Batch experiments were performed to optimize the effect of initial pH, contact time and toxicity-range of DR-31 in order to achieve the optimal conditions for maximum decolourization in continuous cyclic photobioreactor. In batch culture, C. pyrenoidosa exhibited 96% decolourization with 40mgL(-1) dye at pH3. The equilibrium was attained within 30min and the maximum uptake of 30.53mgg(-1) algal biomass was observed during this period. This was found to be fitted well with Langmuir and Freundlich adsorption isotherm. The FT-IR spectra showed a change from -N=N- to N-H suggesting the possible involvement of the azoreductase enzyme. The application of C. pyrenoidosa not only degraded the DR-31 but also improved the quality of water by reducing COD (82.73%), BOD (56.44%), sulphate (54.54%), phosphate (19.88%), and TDS (84.18%) which was further enhanced in continuous cyclic bioreactor treatment. The results clearly showed that C. pyrenoidosa provides an efficient, self-sustainable green technology for decolourization of DR-31 and improved the water quality. PMID- 26826965 TI - Resorption of maxillary incisors after orthodontic treatment--clinical study of risk factors. AB - INTRODUCTION: External apical root resorption (EARR) is one of the major problems associated with orthodontic treatment. Such lesions represent an iatrogenic risk that must be detected as early as possible, with regular radiological follow-up and appropriate therapeutic precautions. The causes and mechanisms leading to susceptibility to root resorption following the application of an orthodontic force are often not clear and are generally said to be of multifactorial origin. The aim of this clinical study was to analyze the factors linked to the occurrence of moderate to severe resorption (MSR) of upper incisors during orthodontic treatment in a group of Moroccan patients treated in the Dento-Facial Orthopedic Department of the Dental Consultation and Treatment Center (Centre de consultation et de traitements dentaires [CCTD]) in Rabat. MATERIAL AND METHODS: A total of 82 patients (28% males, 72% females) aged between 12 and 27, with various malocclusions, who had been treated with fixed appliances for at least 1 year and for whom panoramic X-rays at the start, during and at the end of treatment were available, were selected randomly. The reduction in maxillary incisor root length was evaluated using resorption scores. The factors studied in relation to the risk of occurrence of MSR were: age, sex, treatment duration, extraction or non-extraction, type of malocclusion (Class I arch-length discrepancy, Class II, Class III), the vertical diagnosis (normal, supraocclusion, open bite), presence of dysfunction, impacted canines and root morphology. Statistical analysis was performed using SPSS software, version 18.0. Statistical tests used were: Kaplan-Meier analysis and the univariate and multivariate Cox models for the study of factors associated with MSR. The threshold of significance adopted was 0.05. RESULTS: The factors that were significantly associated with the occurrence of MSR at the level of the upper incisors were: tooth type, with a greater risk for the lateral incisor (HR=3.2 95% CI [2.3-4.5] P<0.001), treatments with extraction (HR=1.64 95% CI [1.16-2.33] P<0.05), the presence of supraocclusion (HR=2.17 95% CI [1.33-3.53] P<0.05) or open bite (HR=3.12 95% CI [1.66-5.86] P<0.001) and root malformation (HR=1.5 95% CI [1.09-2.07] P<0.05). Age, sex, type of malocclusion, dysfunction and impaction of canines were not associated at a statistically significant level with the risk of occurrence of MSR of the upper incisors. CONCLUSION: EARR is difficult to avoid; the orthodontist's role remains crucial in identifying risk factors so as to adopt a treatment strategy taking these factors into account. In our population, the risk of MSR in the upper incisors appeared to increase in treatments with extraction, situations of supraocclusion or open bite, and in the presence of root abnormalities. Finally, clinical recommendations for the prevention of the occurrence of MSR of the maxillary incisors are proposed, taking into account all the risk factors identified. PMID- 26826970 TI - European College of Orthodontics: Commission of affiliation and titularisation. AB - Date of birth: 7 December 1996; sex: male. A. PRETREATMENT RECORDS: 13 years 9 months; 9/2009. DIAGNOSIS: Angle Class I. Skeletal Class I, severe upper and lower tooth-arch discrepancy. Teeth missing prior to treatment: none. TREATMENT PLAN: Extractions of 14-24-34-44. Appliances and devices: bimaxillary multibracket appliances, Roth .022*.028''. Start of treatment: 14 years 10 months; 10/2010. B. POST-TREATMENT RECORD: 1/2012; 16 years. DURATION OF ACTIVE TREATMENT: 26 months. RETENTION: 1/2012. Thermoformed slip-cover retainer. C. POST-RETENTION RECORDS (1 YEAR MINIMUM): 2/2013; 17 years. Date of end of retention: 3/2014. Duration of retention: 26 months. Post-retention period: 6/2015. PMID- 26826971 TI - Load deflection characteristics of square and rectangular archwires. AB - AIMS: To determine and compare the relative stiffness of a large selection of commonly-used square and rectangular steel, super-tempered steel, NiTi, and TMA orthodontic archwires of various cross-sections, in order to provide the clinician with a useful, easy-to-consult guide to archwire sequence selection. MATERIALS AND METHODS: Twenty-four archwires of different cross-section shape, size and material were selected. Each type was subjected to a modified three point bending test, performed in triplicate using an Instron 4467 dynamometer. Each sample was deflected by 1mm, and the corresponding load recorded. The relative stiffness of each archwire sample was calculated, and samples were compared by material and by cross-section. RESULTS: A considerable difference in resistance to deflection was revealed between all the tested archwires. As expected, the resistance to deflection of archwires of the same cross-section was found to increase with increasing stiffness of their construction material. Specifically, steel archwires can be as much as 8 times stiffer than NiTi archwires of the same shape and cross-section, and super-tempered steel archwires are invariably stiffer than traditional steel versions. Marked differences in resistance to deflection were also found between NiTi archwires made of the same material but with different shape characteristics. CONCLUSIONS: In archwires of the same cross-section, steel is always stiffer than TMA and NiTi, and super tempered steel is always stiffer than conventional steels. In archwires of the same material, the stiffness increases with the cross-section, in particular with its height. PMID- 26826972 TI - Partial and total luxations of permanent teeth in children: Clinical management. AB - Dentoalveolar trauma, very frequent during childhood and adolescence, generally results in tooth fracture and/or partial or total luxation. Management of the pulpal and periodontal aspects of these traumatic cases is complex. The prognosis is improved if treatment is initiated promptly. Multidisciplinary management of these situations and regular patient follow-up make it possible to detect complications quickly and take the necessary action to maintain the teeth as long as possible in a healthy periodontal environment that allows harmonious development and the application of appropriate treatment in adulthood. PMID- 26826973 TI - A comparison of the performance of regression models of Amblyomma americanum (L.) (Ixodidae) using life cycle or landscape data from administrative divisions. AB - The distribution of Amblyomma americanum (L.) in the continental United States has been modelled using the reported distribution in counties as "established" (six or more ticks or two or more life stages were recorded during a specified time period), "reported" (fewer than six ticks of a single life stage were recorded), or "absent" (neither of the above categories were met) and a set of environmental and biotic explanatory variables. Categorical (vegetation, climate, and habitat suitability for the main host of the tick) or continuous variables (raw data on temperature, vegetation, and habitat fragmentation), as well as the processes of the tick's life cycle, were tested to build models using multiple logistic regression. The best results were obtained when the life cycle processes were used as descriptors of regressions. Better models derived from life cycle processes were obtained after inclusion of habitat suitability for the white tailed deer (the main host of the tick) and landscape fragmentation. Using this approach, 86% of "absent" and 83% of "established" counties were classified correctly, but all "reported" counties were erroneously classified. Modelling life cycle processes with descriptions of host abundance and habitat fragmentation produced the best outcome when coordinates were missing. When only standard categorical descriptors of climate or vegetation were included in models, results produced poor outcomes. Models were improved with remotely sensed information on temperature and vegetation but produced high rates of misclassification for 14% of "absent", 37% of "established", and 100% of "reported" counties. Modelling produced poor results in the absence of point distributions (coordinates). Therefore, "reported" counties cannot be handled adequately by modelling procedures, probably because this category does not reflect the true status of the tick distribution. We conclude that standard categorical classifications of the distribution of an organism can not be reliably used as input for modelling procedures. PMID- 26826974 TI - A novel spotted fever group Rickettsia infecting Amblyomma parvitarsum (Acari: Ixodidae) in highlands of Argentina and Chile. AB - The tick Amblyomma parvitarsum (Acari: Ixodidae) has established populations in Andean and Patagonic environments of South America. For the present study, adults of A. parvitarsum were collected in highland areas (elevation >3500 m) of Argentina and Chile during 2009-2013, and tested by PCR for rickettsial infection in the laboratory, and isolation of rickettsiae in Vero cell culture by the shell vial technique. Overall, 51 (62.2%) out of 82 A. parvitarsum adult ticks were infected by spotted fever group (SFG) rickettsiae, which generated DNA sequences 100% identical to each other, and when submitted to BLAST analysis, they were 99.3% identical to corresponding sequence of the ompA gene of Rickettsia sp. strain Atlantic rainforest. Rickettsiae were successfully isolated in Vero cell culture from two ticks, one from Argentina and one from Chile. DNA extracted from the third passage of the isolates of Argentina and Chile were processed by PCR, resulting in partial sequences for three rickettsial genes (gltA, ompB, ompA). These sequences were concatenated and aligned with rickettsial corresponding sequences available in GenBank. Phylogenetic analysis revealed that the A. pavitarsum rickettsial agent grouped under high bootstrap support in a clade composed by the SFG pathogens R. sibirica, R. africae, R. parkeri, Rickettsia sp. strain Atlantic rainforest, and two unnamed SFG agents of unknown pathogenicty, Rickettsia sp. strain NOD, and Rickettsia sp. strain ApPR. The pathogenic role of this A. parvitarsum rickettsia cannot be discarded, since several species of tick borne rickettsiae that were considered nonpathogenic for decades are now associated with human infections. PMID- 26826975 TI - Weight bias internalization in treatment-seeking overweight adults: Psychometric validation and associations with self-esteem, body image, and mood symptoms. AB - Internalized weight bias has been previously associated with impairments in eating behaviors, body image, and psychological functioning. The present study explored the psychological correlates and psychometric properties of the Weight Bias Internalization Scale (WBIS) among overweight adults enrolled in a behavioral weight loss program. Questionnaires assessing internalized weight bias, anti-fat attitudes, self-esteem, body image concern, and mood symptoms were administered to 90 obese or overweight men and women between the ages of 21 and 73. Reliability statistics suggested revisions to the WBIS. The resulting 9-item scale was shown to be positively associated with body image concern, depressive symptoms, and stress, and negatively associated with self-esteem. Multiple linear regression models demonstrated that WBIS scores were significant and independent predictors of body image concern, self-esteem, and depressive symptoms. These results support the use of the revised 9-item WBIS in treatment-seeking samples as a reliable and valid measure of internalized weight bias. PMID- 26826976 TI - Respiratory sinus arrhythmia as a predictor of eating disorder symptoms in college students: Moderation by responses to stress and parent psychological control. AB - This longitudinal study examined the prospective contribution of respiratory sinus arrhythmia (RSA), a key physiological indicator of self-regulation, to eating disorder symptoms in college students, and whether this link was moderated by maladaptive responses to stress and parent psychological control. At Wave 1, college students' RSA was measured at rest. At Waves 1 and 2 (six-month follow up), students reported on their eating disorder symptoms, coping and involuntary responses to stress, and perceptions of their parents' use of psychological control. Significant three-way interactions indicated that the link between RSA and subsequent eating disorder symptoms was contingent on responses to stress and parent psychological control. In the context of maladaptive responses to stress and high psychological control, RSA predicted increased eating disorder symptoms over time. In the absence of parent psychological control, high RSA was beneficial in most cases, even when individuals reported maladaptive responses to stress. This study presents novel evidence that high RSA contributes to risk for or resilience to eating disorder symptoms over time. RSA can be protective against eating disorder symptoms, but in some contexts, the self-regulation resources that high RSA provides may be inappropriately applied to eating cognitions and behaviors. This research highlights the importance of examining physiological functioning conjointly with other risk factors as precursors to eating disorder symptoms over time. PMID- 26826977 TI - Direct NOE simulation from long MD trajectories. AB - A software package, MD2NOE, is presented which calculates Nuclear Overhauser Effect (NOE) build-up curves directly from molecular dynamics (MD) trajectories. It differs from traditional approaches in that it calculates correlation functions directly from the trajectory instead of extracting inverse sixth power distance terms as an intermediate step in calculating NOEs. This is particularly important for molecules that sample conformational states on a timescale similar to molecular reorientation. The package is tested on sucrose and results are shown to differ in small but significant ways from those calculated using an inverse sixth power assumption. Results are also compared to experiment and found to be in reasonable agreement despite an expected underestimation of water viscosity by the water model selected. PMID- 26826979 TI - Development and rheological properties of ecological emulsions formulated with a biosolvent and two microbial polysaccharides. AB - The influence of gum concentration and rhamsan/welan gum ratio on rheological properties, droplet size distribution and physical stability of eco-friendly O/W emulsions stabilized by an ecological surfactant were studied in the present work. The emulsions were prepared with 30wt% alpha-pinene, a terpenic solvent and an ecological alternative for current volatile organic compounds. Rheological properties of emulsions showed an important dependence on the two studied variables. Flow curves were fitted to the Cross model and no synergistic effect between rhamsan and welan gums was demonstrated. Emulsions with submicron mean diameters were obtained regardless of the gum concentration or the rhamsan/welan ratio used. Multiple light scattering illustrated that creaming was practically eliminated by the incorporation of polysaccharides. The use of rhamsan and welan gums as stabilizers lead to apparent enhancements in emulsion rheology and physical stability. PMID- 26826978 TI - Escaping the biofilm in more than one way: desorption, detachment or dispersion. AB - Biofilm bacteria have developed escape strategies to avoid stresses associated with biofilm growth, respond to changing environmental conditions, and disseminate to new locations. An ever-expanding body of research suggests that cellular release from biofilms is distinct from a simple reversal of attachment and reversion to a planktonic mode of growth, with biofilm dispersion involving sensing of specific cues, regulatory signal transduction, and consequent physiological alterations. However, dispersion is only one of many ways to escape the biofilm mode of growth. The present review is aimed at distinguishing this active and regulated process of dispersion from the passive processes of desorption and detachment by highlighting the regulatory processes and distinct phenotypes specific to dispersed cells. PMID- 26826980 TI - Condensed tannins in extracts from European medicinal plants and herbal products. AB - Medicinal plant materials are not usually analysed for condensed tannins (CT). Thirty commercially available European medicinal plants and herbal products were screened for CT and fourteen CT samples were analysed in detail. This is also the first comprehensive CT analysis of pine buds, walnut leaves, heather flowers and great water dock roots. Acetone/water extracts contained between 3.2 and 25.9 g CT/100g of extract, had CT with mean degrees of polymerisation of 2.9 to 13.3, procyanidin/prodelphinidin ratios of 1.6/98.4 to 100/0 and cis/trans flavan-3-ol ratios of 17.7/82.3 to 97.3/2.7. The majority of samples contained procyanidins, four contained A-type linkages (blackthorn flowers, heather flowers, bilberry leaves and cowberry leaves) and one sample also had galloylated procyanidins (great water dock roots). PMID- 26826981 TI - Does the gender of parent or child matter in child maltreatment in China? AB - Child maltreatment is a public health problem worldwide, and China is no exception. However, the pattern of child maltreatment remains unknown, including whether the gender of children and their parents has an impact on the occurrence of maltreatment. This study aims at examining the rates and frequency of child maltreatment, including physical abuse, psychological abuse and neglect perpetrated by mothers and fathers. We also test whether the interaction between parents' gender and their child's gender affects the occurrence of child maltreatment in China. 997 children from the China Jintan Child Cohort Study participated in the present study and reported their maltreatment experience perpetrated by their mothers and fathers using the questionnaire, Parent-Child Conflict Tactics Scale (CTSPC_CA). Generalized linear model analyses show that boys were more likely than girls to report physical abuse, and, in particular, boys were more likely than girls to be physically abused by their fathers. On the other hand, mothers were more likely than fathers to exhibit psychological aggression and use corporal punishment for both boys and girls. There was no difference based on the child's or parent's gender in the occurrence of neglect. The findings present empirical evidence that enhances the understanding of the pattern of child maltreatment in China, provide implications for social workers and health professionals to identify children at risk of child maltreatment, and shed light on future research studies. PMID- 26826982 TI - A Kriging surrogate model coupled in simulation-optimization approach for identifying release history of groundwater sources. AB - As the incidence frequency of groundwater pollution increases, many methods that identify source characteristics of pollutants are being developed. In this study, a simulation-optimization approach was applied to determine the duration and magnitude of pollutant sources. Such problems are time consuming because thousands of simulation models are required to run the optimization model. To address this challenge, the Kriging surrogate model was proposed to increase computational efficiency. Accuracy, time consumption, and the robustness of the Kriging model were tested on both homogenous and non-uniform media, as well as steady-state and transient flow and transport conditions. The results of three hypothetical cases demonstrate that the Kriging model has the ability to solve groundwater contaminant source problems that could occur during field site source identification problems with a high degree of accuracy and short computation times and is thus very robust. PMID- 26826983 TI - Mobilization and micellar solubilization of NAPL contaminants in aquifer rocks. AB - Surfactant-enhanced aquifer remediation is often performed to overcome the capillary forces that keep residual NAPL phases trapped within contaminated aquifers. The surfactant selection and displacement mechanism usually depend on the nature of NAPL constituents. For example, micellar solubilization is often used to cleanup DNAPLs from aquifers whereas mobilization is desirable in aquifers contaminated by LNAPLs. Although the majority of crude oils are LNAPLs, they often contain heavy organic macromolecules such as asphaltenes that are classified as DNAPLs. Asphaltenes contain surface-active components that tend to adsorb on rocks, altering their wettability. Previous studies revealed that surfactants that formed Winsor type III microemulsions could promote both mobilization and solubilization. However the extent by which these two mechanisms occur is still unclear, particularly in oil-contaminated aquifers. In this study we investigated the remediation of oil-contaminated aquifers using an environmentally friendly surfactant such as n-Dodecyl beta-D-maltoside. Focus was given on asphaltenes to better understand the mechanisms of surfactant cleanup. Through phase behavior, spontaneous imbibition, dynamic interfacial tension and contact angle measurements, we showed that microemulsions formed by this surfactant are able to mobilize bulk NAPL (containing 9wt.% asphaltenes) in the porous rock and solubilize DNAPL (i.e., 4-6wt.% adsorbed asphaltenes) from the rock surface. Spontaneous imbibition tests, in particular, indicated that the ratio of mobilized to solubilized NAPL is about 6:1. Furthermore, aging the cores in NAPL beyond 3days allowed for more NAPL to be trapped in the large pores of the rock but did not alter the amount of asphaltenes adsorbed on the mineral surface. PMID- 26826984 TI - Is worst-event trauma type related to PTSD symptom presentation and associated features? AB - Posttraumatic stress disorder (PTSD) is generally assessed with reference to a "worst-event" (index) trauma, though little research has examined whether symptom presentation and comorbidity differ across worst-events. Data from individuals meeting lifetime PTSD criteria in the National Comorbidity Survey-Replication (N=398) were used to examine relations between PTSD presentation and comorbidity with the three most commonly reported "worst-event" trauma types: sexual trauma, non-sexual physical violence, and unexpected death of a loved one. Sexual trauma and non-sexual physical violence were associated with more symptomatic presentation of PTSD and lifetime trauma types compared to other worst-events. Non-sexual physical violence was associated with comorbid substance use disorder, and unexpected death of a loved one was associated with comorbid depression. Inclusion of number of lifetime trauma types as a covariate rendered most, but not all associations non-significant. These findings suggest worst-event trauma type is related to some important differences in PTSD presentation. PMID- 26826985 TI - Anaesthetic efficacy of unilamellar and multilamellar liposomal formulations of articaine in inflamed and uninflamed tissue. AB - We compared the efficacy of articaine encapsulated in multilamellar and unilamellar liposomes with that of articaine with epinephrine, after infiltration into inflamed and uninflamed tissue in rats. We encapsulated 4% articaine in multilamellar (articaine:multi) and unilamellar (articaine:uni) liposomes and compared them with 4% articaine with 1:100 000 epinephrine (articaine:epinephrine), in inflamed (plantar incision into the hind paw) and uninflamed (infraorbital nerve block) tissue in rats. Anaesthetic formulations (0.1ml) were injected near the right infraorbital foramen in uninflamed tissue, where success and duration of anaesthesia were assessed by pinching the upper lip every 5 minutes. For inflamed tissue the anaesthetic formulations (0.1ml) were injected laterally into a surgical wound made 24 hours earlier in the plantar region of the rat's right hind paw. The degree of anaesthesia was assessed by application of forces laterally to the wound with electronic von Frey filaments. Articaine:uni resulted in less successful anaesthesia than both articaine:multi (p=1.1x10(-5)) and articaine:epinephrine (p=4.3x10(-8)) in uninflamed tissue, but there were no differences in duration or success of anaesthesia between articaine:epinephrine and articaine:multi. In inflamed tissue articaine:epinephrine gave significantly more effective anaesthesia for longer than articaine:uni (p=2.3x10(-6)), and articaine:epinephrine (p=1.8x10(-6)) formulations, which did not differ from each other. Multilamellar liposomal articaine could be an option for local anaesthesia in uninflamed tissues. However, articaine with epinephrine gave better results than liposomal formulations in inflamed tissue. PMID- 26826986 TI - [Hantavirus pulmonary syndrome in Buenos Aires, 2009-2014]. AB - Andes virus is the causative agent of hantavirus pulmonary syndrome (HPS) in Argentina and neighboring countries. In our country four different areas are affected: Northwest, Southwest, Central and Northeast, where distinct Andes virus genotypes were characterized. Three genotypes were described in Buenos Aires province (Central area): AND-Buenos Aires, AND-Lechiguanas and AND-Plata. In this work, we considered all HPS cases confirmed by ELISA and real time RT-PCR during the period 2009-2014 in Buenos Aires province. The annual distribution, fatality rate and geographic distribution were analyzed. We also analyzed the genotypes involved by RT-PCR and nucleotide sequencing. Finally we evaluated epidemiological data in order to establish the route of transmission. We analyzed 1386 suspect cases of hantavirus infection from Buenos Aires province and we confirmed 88 cases of Hantavirus Pulmonary Syndrome during 2009-2014. The overall average was 14.3 cases per year. The occurrence of a HPS outbreak was confirmed in Buenos Aires province during 2013, showing a 3 fold increase in case number compared to the annual average between 2009 and 2012, tending to normalize during 2014. The overall lethality was 25.6%, with a maximum value of 45.5% in 2011. Genotype analysis was performed in 30.7% of confirmed cases, AND-BsAs show the highest incidence, it was characterized in 72% of the studied cases. Epidemiological data and results of viral genome comparison strongly suggest person-to-person transmission in the three clusters of two cases described in our study. PMID- 26826987 TI - [Primary pyomyositis. Review of 32 cases diagnosed by ultrasound]. AB - Primary pyomyositis is a bacterial infection of striated muscle which is acquired by hematogenous route. It is related to risk factors such as HIV/aids and other immuno suppressing diseases, and can be associated with local muscle stress factors. The most frequent etiology is Staphylococcus aureus. Its diagnostic delay may cause a fatal evolution. In this series 32 patients with primary pyomyositis diagnosed by ultrasound were evaluated. The most frequent risk factor was HIV/aids (61%). Local factors were detected in 21 (66%) cases: first, the practice of football. The monofocal form was observed in 19 (59%), the most commonly affected muscles were quadriceps, calves and psoas. Samples for bacteriological study were obtained in 30 cases, 22 blood culture and 27 abscess materials. In 30 cases the etiologic agent was isolated. Staphylococcus aureus accounted for 83.3% (25 cases) and Escherichia coli, Nocardia spp., Streptococcus agalactiae, nontuberculous mycobacteria, Pseudomonas aeruginosa were isolated in one case each. Seventeen patients received surgical treatment, aspirative punctures, 9; antibiotics alone, 4. Twenty eight (93.3%) patients had a good evolution; deaths, 2 (6.6%); unknown, 2. Main conclusions of this study were: due to the diverse and changing etiology of the primary pyomyositis it is important to recognize the etiological agent involved and their antibiotic susceptibility. The ultrasound performed the study in real time so it can be used to guide the puncture and to facilitate the immediate diagnosis. This makes the difference with other techniques and transforms it into a first-line method for the study of this disease. PMID- 26826988 TI - [Severe asthma]. AB - The objectives of this work were to investigate the frequency of severe asthma (SA) according to WHO definition and to compare SA patients' characteristics with those of non-severe asthma (NSA); secondly, to investigate the level of control reached throughout a period of regular treatment. Between 1-1-2005 and 12-31 2014, 471 medical records from patients with bronchial asthma assisted in Buenos Aires City were analyzed. SA frequency was 40.1% (189/471), being significantly higher among patients from the public health system (47.7%, 108/226 vs. 33%, 81/245, p = 0.001). SA patients were older than NSA ones (51.3 +/- 17.4 vs. 42.6 +/- 17.1 years, p = 0.000), presented longer time since onset of the disease (median 30 vs. 20 years, p = 0.000), lower educational levels (secondary level or higher 41.7% vs. 58.1%, p = 0.000), lower frequency of rhinitis (47% vs. 60.6%, p = 0.004), more severe levels of airway obstruction (FEV% 50.2 +/- 13.7 vs. 77.7 +/- 12.4, p = 0.000), more frequent antecedents of Near Fatal Asthma (11.1% vs. 2.8%, p = 0.000), higher levels of serum IgE (median of 410 vs. 279 UI/l, p = 0.01) and higher demand of systemic steroids requirements and hospitalizations (68.7% vs. 50.7%, p = 0.000 and 37.5% vs. 15.9%, p = 0.000, respectively). A 30.6% of SA patients (58/189) reached a follow-up period of 12 months, 13 (22.5%) of whom reached the controlled asthma level. The frequency of SA found seems to be considerable. Multicenter studies to investigate the levels of control reached by SA patients with access to proper treatment are recommended. PMID- 26826990 TI - [Successful treatment of a cervical heterotopic pregnancy following an in vitro fertilization procedure]. AB - A 37-year-old nulligravida infertile female had a cervical heterotopic pregnancy following an in vitro fertilization procedure. Early intervention on the 6th week of gestation with a manual vacuum aspirator reached to remove the cervical pregnancy. Ligation of the descending cervical branches of the uterine arteries and a cervical cerclage, were placed before the aspiration, for prevention of possible hemorrhage. Successful removal of the cervical pregnancy was achieved with only mild bleeding. An intrauterine pregnancy progressed to viability without complications, resulting in a vaginal delivery of a preterm live-birth at 35.4 weeks, of a male that weighted 2740 g. PMID- 26826989 TI - [Cercarial dermatitis of bathers in northern Argentine Patagonia]. AB - The cercarial dermatitis is a zoonotic, summer, skin-disease, caused by a swimming larva (cercaria) of a schistosomatid trematode. This larva accidentally penetrates the skin of people in the water, causing an allergic reaction, which is not always reported in health centers, so it is difficult to determine its incidence. Cases have been registered worldwide, including Argentina, although the epidemiological studies were performed only in the Northern Hemisphere. In this survey the epidemiology of cercarial dermatitis was studied in three Patagonian lakes watering places, Pellegrini, Mari Menuco, and Puelo, where surveys were conducted during summers of 2012-2013 and 2013-2014. The risk factors were analyzed and grouped in "personal characteristics", "use of the recreational resource", and "prevention measures". At the Pellegrini Lake, the people's sensitivity included in "personal characteristics" was the only determining factor for the occurrence of this zoonosis, mean while in Mari Menuco Lake, the bathing time and distance from the coast, and the use of lotions would affect the occurrence of swimmer's itch. In Puelo Lake, no cases were recorded during the study period. PMID- 26826991 TI - [Davidenkow syndrome. A rare peripheral neuropathy]. AB - A different and rare type of atrophy with a predominant pattern in scapulo peroneal distribution was described by Davidenkow in 1939. The syndrome was characterized by some researchers as a variant of Charcot-Marie-Tooth disease, however Davidenkow noticed that clinical and laboratorial manifestations did not corroborate exactly with this hypothesis. We describe a case of a female patient, 39 years-old, clinical picture similar to the syndrome described by Davidenkow, presenting scapulo-peroneal atrophy. Her first symptoms had appeared when she was 24, initially with proximal motor weakness in the upper limbs. This patient did not have family history of myopathy or neuropathy. Several tests were performed to exclude other syndromes that could be included in the differential diagnosis, by testing gene mutation, in addition to the physical examination and electromyography. The large spectrum of neuromuscular diseases makes difficult the diagnosis of Davidenkow's syndrome which always should be considered in the differential diagnosis. PMID- 26826992 TI - [Subcutaneous immunoglobulin. Treatment in chronic inflammatory demyelinating polyradiculo-neuropathy]. AB - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired disease that may affect nerve roots and peripheral nerves. Despite its low incidence, diagnosis is particularly important because there are different effective treatments. Human immunoglobulin is one of the mainstays of the treatment. Although there are few studies up to date, subcutaneous immunoglobulin (IgSC) has been proposed as an alternative to intravenous administration with similar efficacy. We present three cases with definite CIDP, classified according to the European Federation of Neurological Societies / Peripheral Nerve, Society (EFNS /PNS) criteria in which was used SCIgG as a treatment after success with the intravenous route. The Overall Neuropathy Limitations Scale (ONLS) was used to estimate the changes in the muscular strength before and after treatment. PMID- 26826993 TI - [Olfactory neuroblastoma]. PMID- 26826994 TI - [Lipoma arborescens with atypical location]. PMID- 26826995 TI - [Medicine at the "edge of chaos". Life, entropy and complexity]. AB - The aim of this paper is to help physicians and health professionals, who constantly seek to improve their knowledge for the benefit of the ill, to incorporate new conceptual and methodological tools to understand the complexity inherent to the field of medicine. This article contains notions that are unfamiliar to these professionals and are intended to foster reflection and learning. It poses the need to define life from a thermodynamic point of view, linking it closely to complex systems, nonlinear dynamics and chaotic behavior, as well as to redefine conventional physiological control mechanisms based on the concept of homeostasis, and to travel the path that starts with the search for extraterrestrial life up to exposing medicine "near the edge of chaos". Complexity transcends the biological aspects; it includes a subjective and symbolic/social dimension. Viewing disease as a heterogeneous and multi-causal phenomenon can give rise to new approaches for the sick. PMID- 26826996 TI - [Elephants, longevity, cancer and p53]. PMID- 26826997 TI - [SIADH syndrome that precedes the diagnosis of pulmonary neoplasia]. PMID- 26826998 TI - Effect of Jagged-1 and Dll-1 on osteogenic differentiation by stem cells from human exfoliated deciduous teeth. AB - OBJECTIVE: The aim of the present study was to determine the influence of Notch ligands, Jagged-1 and Dll-1, on osteogenic differentiation by stem cells from human exfoliated deciduous teeth. DESIGN: Notch ligands were immobilized on tissue culture surface using an indirect affinity immobilization technique. Cells from the remaining of dental pulp tissues from human deciduous teeth were isolated and characterized using flow cytometry and differentiation assay. Alkaline phosphatase (ALP) enzymatic activity, osteogenic marker gene expression, and mineralization were determined using ALP assay, real-time polymerase chain reaction, and alizarin red staining, respectively. RESULTS: The isolated cells exhibited CD44, CD90, and CD105 expression but lack of CD45 expression. Further, these cells were able to differentiate toward osteogenic lineage. The upregulation of HES-1 and HEY-1 was observed in those cells on Dll-1 and Jagged-1 coated surface. The significant increase of ALP activity and mineralization was noted in those cells seeded on Jagged-1 surface and these results were attenuated when cells were pretreated with gamma secretase inhibitor. The significant upregulation of ALP and collagen type I gene expression was also observed in those cells seeded on Jagged-1 surface. The inconsistent Dll-1 induced osteogenic differentiation was found and high Dll-1 immobilized dose (50 nM) slightly enhanced alkaline phosphatase enzymatic activity. However, the statistical significant difference was not obtained as compared to the hFc control. CONCLUSION: The surface immobilization of Notch ligands, Jagged-1 and Dll-1, likely to enhance osteogenic differentiation of SHEDs. However, Jagged-1 had more ability in enhancing osteogenic differentiation than Dll-1 in our model. PMID- 26827000 TI - Atmospheric noise of a breaking tidal bore. AB - A tidal bore is a surge of waters propagating upstream in an estuary as the tidal flow turns to rising and the flood tide propagates into a funnel-shaped system. Large tidal bores have a marked breaking roller. The sounds generated by breaking tidal bores were herein investigated in the field (Qiantang River) and in laboratory. The sound pressure record showed two dominant periods, with some similarity with an earlier study [Chanson (2009). J. Acoust. Soc. Am. 125(6), 3561-3568]. The two distinct phases were the incoming tidal bore when the sound amplitude increased with the approaching bore, and the passage of the tidal bore in front of the microphone when loud and powerful noises were heard. The dominant frequency ranged from 57 to 131 Hz in the Qiantang River bore. A comparison between laboratory and prototype tidal bores illustrated both common features and differences. The low pitch sound of the breaking bore had a dominant frequency close to the collective oscillations of bubble clouds, which could be modeled with a bubble cloud model using a transverse dimension of the bore roller. The findings suggest that this model might be over simplistic in the case of a powerful breaking bore, like that of the Qiantang River. PMID- 26827001 TI - Field observation of low-to-mid-frequency acoustic propagation characteristics of an estuarine salt wedge. AB - The estuarine environment often hosts a salt wedge, the stratification of which is a function of the tide's range and speed of advance, river discharge volumetric flow rate, and river mouth morphology. Competing effects of temperature and salinity on sound speed in this stratified environment control the degree of acoustic refraction occurring along an acoustic path. A field experiment was carried out in the Columbia River Estuary to test the hypothesis: the estuarine salt wedge is acoustically observable in terms of low-to-mid frequency acoustic propagation. Linear frequency-modulated acoustic signals in the 500-2000 Hz band were transmitted during the advance and retreat of the salt wedge during May 27-29, 2013. Results demonstrate that the salt wedge front is the dominant physical mechanism controlling acoustic propagation in this environment: received signal energy is relatively stable before and after the passage of the salt wedge front when the acoustic path consists of a single medium (either entirely fresh water or entirely salt water), and suffers a 10-15 dB loss and increased variability during salt wedge front passage. Physical parameters and acoustic propagation modeling corroborate and inform the acoustic observations. PMID- 26826999 TI - The neural encoding of formant frequencies contributing to vowel identification in normal-hearing listeners. AB - Even though speech signals trigger coding in the cochlea to convey speech information to the central auditory structures, little is known about the neural mechanisms involved in such processes. The purpose of this study was to understand the encoding of formant cues and how it relates to vowel recognition in listeners. Neural representations of formants may differ across listeners; however, it was hypothesized that neural patterns could still predict vowel recognition. To test the hypothesis, the frequency-following response (FFR) and vowel recognition were obtained from 38 normal-hearing listeners using four different vowels, allowing direct comparisons between behavioral and neural data in the same individuals. FFR was employed because it provides an objective and physiological measure of neural activity that can reflect formant encoding. A mathematical model was used to describe vowel confusion patterns based on the neural responses to vowel formant cues. The major findings were (1) there were large variations in the accuracy of vowel formant encoding across listeners as indexed by the FFR, (2) these variations were systematically related to vowel recognition performance, and (3) the mathematical model of vowel identification was successful in predicting good vs poor vowel identification performers based exclusively on physiological data. PMID- 26827002 TI - Lateralization of stimuli with alternating interaural time differences: The role of monaural envelope cues. AB - A temporally acute binaural system can help to resolve inherent fluctuations in binaural information that are often present in complex auditory scenes. Using a broadband noise stimulus that rapidly alternates between two different values of interaural time difference (ITD), the ability of the binaural system to hear the lateral position resulting from one of the ITD values was investigated. Results show that listeners are able to accurately lateralize brief noise tokens of only 3-7 ms in duration. In two subsequent experiments, the role of an amplitude modulation (AM) imposed on the ITD-switching stimulus used in the first experiment was tested. For wideband stimuli, the temporal position of the ITD target relative to the phase of the AM did not influence absolute lateralization or detection performance. When the stimuli were narrowband, however, detection of the ITD target was best when temporally positioned in the rising portion of the AM. These experiments illustrate that the auditory system is capable of making accurate lateral estimates of very brief moments of ITD information. Furthermore, for these instantaneous changes in ITD information, the stimulus bandwidth can influence the role of envelope cues for the readout of binaural information. PMID- 26827003 TI - In situ measurements of the oblique incidence sound absorption coefficient for finite sized absorbers. AB - Absorption coefficients are mostly measured in reverberation rooms or with impedance tubes. Since these methods are only suitable for measuring the random incidence and the normal incidence absorption coefficient, there exists an increasing need for absorption coefficient measurement of finite absorbers at oblique incidence in situ. Due to the edge diffraction effect, oblique incidence methods considering an infinite sample fail to measure the absorption coefficient at large incidence angles of finite samples. This paper aims for the development of a measurement method that accounts for the finiteness of the absorber. A sound field model, which accounts for scattering from the finite absorber edges, assuming plane wave incidence is derived. A significant influence of the finiteness on the radiation impedance and the corresponding absorption coefficient is found. A finite surface method, which combines microphone array measurements over a finite sample with the sound field model in an inverse manner, is proposed. Besides, a temporal subtraction method, a microphone array method, impedance tube measurements, and an equivalent fluid model are used for validation. The finite surface method gives promising agreement with theory, especially at near grazing incidence. Thus, the finite surface method is proposed for further measurements at large incidence angles. PMID- 26827004 TI - Transmission beam characteristics of a Risso's dolphin (Grampus griseus). AB - The echolocation system of the Risso's dolphin (Grampus griseus) remains poorly studied compared to other odontocete species. In this study, echolocation signals were recorded from a stationary Risso's dolphin with an array of 16 hydrophones and the two-dimensional beam shape was explored using frequency-dependent amplitude plots. Click source parameters were similar to those already described for this species. Centroid frequency of click signals increased with increasing sound pressure level, while the beamwidth decreased with increasing center frequency. Analysis revealed primarily single-lobed, and occasionally vertically dual-lobed, beam shapes. Overall beam directivity was found to be greater than that of the harbor porpoise, bottlenose dolphin, and a false killer whale. The relationship between frequency content, beam directivity, and head size for this Risso's dolphin deviated from the trend described for other species. These are the first reported measurements of echolocation beam shape and directivity in G. griseus. PMID- 26827005 TI - Robust source-range estimation using the array/waveguide invariant and a vertical array. AB - The array invariant based on beam-time migration has been proposed for source range estimation using a horizontal or vertical array (VA), with no need for forward model computations. The approach has been demonstrated successfully with experimental data in shallow water using a horizontal towed array. Recently, the array invariant has been shown to be a special case of the waveguide invariant theory. In this paper, the unified array/waveguide invariant approach to source range estimation is applied to a short-aperture VA in a fluctuating ocean environment over a one-day period. Specifically, the mean range estimates using a 12-m long VA in ~100 m deep water are <8% relative error for a source (2-3 kHz) at 6-km range, demonstrating the robustness of this approach. PMID- 26827006 TI - Sequential inversion of modal data for sound attenuation in sediment at the New Jersey Shelf. AB - This paper presents a method for estimating bottom geoacoustic properties especially the sediment attenuation from information contained in normal modes of a broadband signal. Propagating modes are resolved using the time-warping technique applied to signals from light bulb sound sources deployed at ranges of 5 and 7 km in the Shallow Water '06 experiment. A sequential inversion approach is designed that uses specific features of the acoustic data that are highly sensitive to specific geoacoustic model parameters. The first feature is the modal group speed, which is inverted for seabed sound speed, density, and sediment thickness. The second feature is the modal depth function for inverting receiver depths. The third feature is related to the modal coefficient spectra, and this is inverted for source depth and sediment attenuation. In each subsequent stage, estimates from the previous stage(s) are used as known values. The sequential inversion is stable and generates estimates for the geoacoustic model parameters that agree very well with results from other experiments carried out in the same region. Notably, the inversion obtains an estimated attenuation of 0.078 dB/lambda in the band 120-180 Hz for the de-watered marine sediment characteristic of the continental shelf at the site. PMID- 26827007 TI - Characterizing large river sounds: Providing context for understanding the environmental effects of noise produced by hydrokinetic turbines. AB - Underwater noise associated with the installation and operation of hydrokinetic turbines in rivers and tidal zones presents a potential environmental concern for fish and marine mammals. Comparing the spectral quality of sounds emitted by hydrokinetic turbines to natural and other anthropogenic sound sources is an initial step at understanding potential environmental impacts. Underwater recordings were obtained from passing vessels and natural underwater sound sources in static and flowing waters. Static water measurements were taken in a lake with minimal background noise. Flowing water measurements were taken at a previously proposed deployment site for hydrokinetic turbines on the Mississippi River, where sounds created by flowing water are part of all measurements, both natural ambient and anthropogenic sources. Vessel sizes ranged from a small fishing boat with 60 hp outboard motor to an 18-unit barge train being pushed upstream by tugboat. As expected, large vessels with large engines created the highest sound levels, which were, on average, 40 dB greater than the sound created by an operating hydrokinetic turbine. A comparison of sound levels from the same sources at different distances using both spherical and cylindrical sound attenuation functions suggests that spherical model results more closely approximate observed sound attenuation. PMID- 26827008 TI - Acoustic impedance of micro perforated membranes: Velocity continuity condition at the perforation boundary. AB - The classic analytical model for the sound absorption of micro perforated materials is well developed and is based on a boundary condition where the velocity of the material is assumed to be zero, which is accurate when the material vibration is negligible. This paper develops an analytical model for finite-sized circular micro perforated membranes (MPMs) by applying a boundary condition such that the velocity of air particles on the hole wall boundary is equal to the membrane vibration velocity (a zero-slip condition). The acoustic impedance of the perforation, which varies with its position, is investigated. A prediction method for the overall impedance of the holes and the combined impedance of the MPM is also provided. The experimental results for four different MPM configurations are used to validate the model and good agreement between the experimental and predicted results is achieved. PMID- 26827010 TI - Sub-harmonic broadband humps and tip noise in low-speed ring fans. AB - A joint experimental and numerical study has been achieved on a low-speed axial ring fan in clean inflow. Experimental evidence shows large periodic broadband humps at lower frequencies than the blade passing frequencies and harmonics even at design conditions. These sub-harmonic humps are also found to be sensitive to the fan process and consequently to its tip geometry. Softer fans yield more intense humps more shifted to lower frequencies with respect to the fan harmonics. Unsteady turbulent flow simulations of this ring fan mounted on a test plenum have been achieved by four different methods that have been validated by comparing with overall performances and detailed hot-wire velocity measurements in the wake. Noise predictions are either obtained directly or are obtained through Ffowcs Williams and Hawkings' analogy, and compared with narrowband and third-octave power spectra. All unsteady simulations correctly capture the low flow rates, the coherent vortex dynamics in the tip clearance and consequently the noise radiation dominated by the tip noise in the low- to mid-frequency range. Yet, only the scale-adaptive simulation and the lattice Boltzmann method simulations which can describe most of the turbulent structures accurately provide the proper spectral shape and levels, and consequently the overall sound power level. PMID- 26827009 TI - In-plane and out-of-plane motions of the human tympanic membrane. AB - Computer-controlled digital holographic techniques are developed and used to measure shape and four-dimensional nano-scale displacements of the surface of the tympanic membrane (TM) in cadaveric human ears in response to tonal sounds. The combination of these measurements (shape and sound-induced motions) allows the calculation of the out-of-plane (perpendicular to the surface) and in-plane (tangential) motion components at over 1,000,000 points on the TM surface with a high-degree of accuracy and sensitivity. A general conclusion is that the in plane motion components are 10-20 dB smaller than the out-of-plane motions. These conditions are most often compromised with higher-frequency sound stimuli where the overall displacements are smaller, or the spatial density of holographic fringes is higher, both of which increase the uncertainty of the measurements. The results are consistent with the TM acting as a Kirchhoff-Love's thin shell dominated by out-of-plane motion with little in-plane motion, at least with stimulus frequencies up to 8 kHz. PMID- 26827011 TI - Impulse source localization in an urban environment: Time reversal versus time matching. AB - This study investigates two approaches for localizing an impulse sound source with distributed sensors in an urban environment under controlled processing time. In both approaches, the numerical model used for calculating the sound propagation is a finite-difference time-domain (FDTD) model. The simulations are drastically accelerated by restricting to the lower frequencies of the impulse signals and are evaluated against in situ measurements. The first tested localization technique relies on the time reversal of the measurements with the model. In the second technique, the source is localized by matching the observed differences in the first times of arrival of the signals to those obtained from a pre-defined database of simulations with known source positions. The localization performance is physically investigated on the basis of the measurements, considering two source positions and all possible combinations from 5 to 15 microphones. The time matching localization attains an accuracy of 10 m, which is targeted in this study, in the vast majority of the configurations. In comparison, the time reversal localization is affected by the weakness of contributions from sensors masked and distant from the source. Practical requirements are also discussed, such as real-time constraints, hardware and description of the urban environment. PMID- 26827012 TI - A semi-numerical model for near-critical angle scattering. AB - Numerous phenomena in the fields of physics and mathematics as seemingly different as seismology, ultrasonics, crystallography, photonics, relativistic quantum mechanics, and analytical number theory are described by integrals with oscillating integrands that contain three coalescing criticalities, a branch point, stationary phase point, and pole as well as accumulation points at which the speed of integrand oscillation is infinite. Evaluating such integrals is a challenge addressed in this paper. A fast and efficient numerical scheme based on the regularized composite Simpson's rule is proposed, and its efficacy is demonstrated by revisiting the scattering of an elastic plane wave by a stress free half-plane crack embedded in an isotropic and homogeneous solid. In this canonical problem, the head wave, edge diffracted wave, and reflected (or compensating) wave each can be viewed as a respective contribution of a branch point, stationary phase point, and pole. The proposed scheme allows for a description of the non-classical diffraction effects near the "critical" rays (rays that separate regions irradiated by the head waves from their respective shadow zones). The effects include the spikes present in diffraction coefficients at the critical angles in the far field as well as related interference ripples in the near field. PMID- 26827013 TI - Hyperarticulation in Lombard speech: Global coordination of the jaw, lips and the tongue. AB - Over the last century, researchers have collected a considerable amount of data reflecting the properties of Lombard speech, i.e., speech in a noisy environment. The documented phenomena predominately report effects on the speech signal produced in ambient noise. In comparison, relatively little is known about the underlying articulatory patterns of Lombard speech, in particular for lingual articulation. Here the authors present an analysis of articulatory recordings of speech material in babble noise of different intensity levels and in hypoarticulated speech and report quantitative differences in relative expansion of movement of different articulatory subsystems (the jaw, the lips and the tongue) as well as in relative expansion of utterance duration. The trajectory modifications for one articulator can be relatively reliably predicted by those for another one, but subsystems differ in a degree of continuity in trajectory expansion elicited across different noise levels. Regression analysis of articulatory modifications against durational expansion shows further qualitative differences between the subsystems, namely, the jaw and the tongue. The findings are discussed in terms of possible influences of a combination of prosodic, segmental, and physiological factors. In addition, the Lombard effect is put forward as a viable methodology for eliciting global articulatory variation in a controlled manner. PMID- 26827014 TI - Resonance scattering by fish schools: A comparison of two models. AB - The effective medium method is used to investigate resonance scattering from schools of fish with gas-filled swim bladders, as a function of frequency and azimuth. Calculations are also performed with a coupled differential equation model, which incorporates both multiple scattering between fish and wave interference interactions of their scattered fields [Feuillade, Nero, and Love, J. Acoust. Soc. Am. 99, 196-208 (1996)]. A theoretical comparison of the models for idealized spherical schools shows good agreement over the entire resonance region in the forward direction, where interference interactions have a minimal effect. Good agreement is also seen in back scattering at low frequencies, where the wavelength lambda>=4s, and s is the average nearest neighbor fish separation. If lambda<4s, the models diverge in back scattering, and the effective medium method fails. This can be critically important when migrations of schools to deeper water cause the collective resonance frequency to increase. Multiple scattering interactions are negligible when |4pinf(b)(2)/k|?0.01, where n is the fish number density, f(b) is the individual fish scattering amplitude, and k=2pi/lambda. A comparison with forward scattering data shows very good agreement for both models, and indicates a method for estimating fish abundance. For back scattering data, the effective medium method diverges strongly when lambda<4s. PMID- 26827015 TI - Development of a standing wave apparatus for calibrating acoustic vector sensors and hydrophones. AB - An apparatus was developed to calibrate acoustic hydrophones and vector sensors between 25 and 2000 Hz. A standing wave field is established inside a vertically oriented, water-filled, elastic-walled waveguide by a piston velocity source at the bottom and a pressure-release boundary condition at the air/water interface. A computer-controlled linear positioning system allows a device under test to be precisely located in the water column while the acoustic response is measured. Some of the challenges of calibrating hydrophones and vector sensors in such an apparatus are discussed, including designing the waveguide to mitigate dispersion, understanding the impact of waveguide structural resonances on the acoustic field, and developing algorithms to post-process calibration measurement data performed in a standing wave field. Data from waveguide characterization experiments and calibration measurements are presented and calibration uncertainty is reported. PMID- 26827017 TI - Characterization and reduction of flow separation in jet pumps for laminar oscillatory flows. AB - A computational fluid dynamics model is used to predict the oscillatory flow through tapered cylindrical tube sections (jet pumps). The asymmetric shape of jet pumps results in a time-averaged pressure drop that can be used to suppress Gedeon streaming in closed-loop thermoacoustic devices. However, previous work has shown that flow separation in the diverging flow direction counteracts the time-averaged pressure drop. In this work, the characteristics of flow separation in jet pumps are identified and coupled with the observed jet pump performance. Furthermore, it is shown that the onset of flow separation can be shifted to larger displacement amplitudes by designs that have a smoother transition between the small opening and the tapered surface of the jet pump. These design alterations also reduce the duration of separated flow, resulting in more effective and robust jet pumps. To make the proposed jet pump designs more compact without reducing their performance, the minimum big opening radius that can be implemented before the local minor losses have an influence on the jet pump performance is investigated. To validate the numerical results, they are compared with experimental results for one of the proposed jet pump designs. PMID- 26827019 TI - A multimodal spectral approach to characterize rhythm in natural speech. AB - Human utterances demonstrate temporal patterning, also referred to as rhythm. While simple oromotor behaviors (e.g., chewing) feature a salient periodical structure, conversational speech displays a time-varying quasi-rhythmic pattern. Quantification of periodicity in speech is challenging. Unimodal spectral approaches have highlighted rhythmic aspects of speech. However, speech is a complex multimodal phenomenon that arises from the interplay of articulatory, respiratory, and vocal systems. The present study addressed the question of whether a multimodal spectral approach, in the form of coherence analysis between electromyographic (EMG) and acoustic signals, would allow one to characterize rhythm in natural speech more efficiently than a unimodal analysis. The main experimental task consisted of speech production at three speaking rates; a simple oromotor task served as control. The EMG-acoustic coherence emerged as a sensitive means of tracking speech rhythm, whereas spectral analysis of either EMG or acoustic amplitude envelope alone was less informative. Coherence metrics seem to distinguish and highlight rhythmic structure in natural speech. PMID- 26827018 TI - Individual lipid encapsulated microbubble radial oscillations: Effects of fluid viscosity. AB - Ultrasound-stimulated microbubble dynamics have been shown to be dependent on intrinsic bubble properties, including size and shell characteristics. The effect of the surrounding environment on microbubble response, however, has been less investigated. In particular, microbubble optimization studies are generally conducted in water/saline, characterized by a 1 cP viscosity, for application in the vasculature (i.e., 4 cP). In this study, ultra-high speed microscopy was employed to investigate fluid viscosity effects on phospholipid encapsulated microbubble oscillations at 1 MHz, using a single, eight-cycle pulse at peak negative pressures of 100 and 250 kPa. Microbubble oscillations were shown to be affected by fluid viscosity in a size- and pressure-dependent manner. In general, the oscillation amplitudes exhibited by microbubbles between 3 and 6 MUm in 1 cP fluid were larger than in 4 cP fluid, reaching a maximum of 1.7-fold at 100 kPa for microbubbles 3.8 MUm in diameter and 1.35-fold at 250 kPa for microbubbles 4.8 MUm in diameter. Simulation results were in broad agreement at 250 kPa, however generally underestimated the effect of fluid viscosity at 100 kPa. This is the first experimental demonstration documenting the effects of surrounding fluid viscosity on microbubble oscillations, resulting in behavior not entirely predicted by current microbubble models. PMID- 26827020 TI - Vibroacoustics of orthotropic plates ribbed in both directions: Application to stiffened rectangular wood panels. AB - This paper is focused on the vibroacoustic behavior of a rectangular ribbed wood panel. This is done by developing an analytical model based on a variational approach, taking into account the kinetic and strain energies of a special orthotropic plate, 11 ribs oriented in a first direction and 1 other strong stiffener oriented in the perpendicular direction, which are considered as beams tied to the plate. A modal decomposition is adopted on the basis of the simply supported orthotropic plate. This allows calculating the modes of the wood panel (ribbed modes) in the frequency range 0-5000 Hz. The acoustical radiation of the baffled panel is also calculated. The radiation coefficients of the ribbed modes are presented and compared, when possible, to similar unribbed plate modes. Finally, the vibroacoustic analysis of the structure shows that an excitation placed on the hard point makes the panel particularly radiative and decreases the apparent critical frequency. PMID- 26827021 TI - Localization-in-noise and binaural medial olivocochlear functioning in children and young adults. AB - Children as young as 5 yr old localize sounds as accurately as adults in quiet in the frontal hemifield. However, children's ability to localize in noise and in the front/back (F/B) dimension are scantily studied. To address this, the first part of this study investigated localization-in-noise ability of children vs young adults in two maskers: broadband noise (BBN) and speech-babble (SB) at three signal-to-noise ratios: -12, -6, and 0 dB. In the second part, relationship between binaural medial olivocochlear system (MOC) function and localization-in noise was investigated. In both studies, 21 children and 21 young adults participated. Results indicate, while children are able to differentiate sounds arriving in the F/B dimension on par with adults in quiet and in BBN, larger differences were found for SB. Accuracy of children's localization in noise (for both maskers) in the lateral plane was also poorer than adults'. Significant differences in binaural MOC interaction (mBIC; the difference between the sum of two monaural- and binaural-MOC strength) between adults and children were also found. For reasons which are not clear, adult F/B localization in BBN correlates better with mBIC while children's F/B localization in SB correlated better with binaural MOC strength. PMID- 26827022 TI - Leading-order cross term correction of three-dimensional parabolic equation models. AB - The issue of handling a leading-order cross-multiplied term in three-dimensional (3D) parabolic equation (PE) based models is addressed. In particular, numerical results obtained incorporating a leading-order cross-term correction in an existing 3D PE model, written in cylindrical coordinates, based on higher-order Pade approximations in both depth and azimuth, and a splitting operator technique are reported. Note that the numerical algorithm proposed in this paper could be used in the future to update any 3D PE codes that neglect cross terms and use a splitting numerical technique. The 3D penetrable wedge benchmark problem is chosen to illustrate the accuracy of the now-fully wide-angle enhanced 3D PE model. The comparisons with a 3D reference solution based on the image source clearly show that handling the leading-order cross term in the 3D PE computation is sufficient to remove the phase errors inherent to any 3D PE models that neglect cross terms in their formulations. PMID- 26827024 TI - On the acoustic analysis and optimization of ducted ventilation systems using a sub-structuring approach. AB - This paper presents a general sub-structuring approach to predict the acoustic performance of ducted ventilation systems. The modeling principle is to determine the subsystem characteristics by calculating the transfer functions at their coupling interfaces, and the assembly is enabled by using a patch-based interface matching technique. For a particular example of a bended ventilation duct connecting an inlet and an outlet acoustic domain, a numerical model is developed to predict its sound attenuation performance. The prediction accuracy is thoroughly validated against finite element models. Through numerical examples, the rigid-walled duct is shown to provide relatively weak transmission loss (TL) across the frequency range of interest, and exhibit only the reactive behavior for sound reflection. By integrating sound absorbing treatment such as micro perforated absorbers into the system, the TL can be significantly improved, and the system is seen to exhibit hybrid mechanisms for sound attenuation. The dissipative effect dominates at frequencies where the absorber is designed to be effective, and the reactive effect provides compensations at the absorption valleys attributed to the resonant behavior of the absorber. This ultimately maintains the system TL at a relatively high level across the entire frequency of interest. The TL of the system can be tuned or optimized in a very efficient way using the proposed approach due to its modular nature. It is shown that a balance of the hybrid mechanism is important to achieve an overall broadband attenuation performance in the design frequency range. PMID- 26827023 TI - Varying irrelevant phonetic features hinders learning of the feature being trained. AB - Learning to distinguish nonnative words that differ in a critical phonetic feature can be difficult. Speech training studies typically employ methods that explicitly direct the learner's attention to the relevant nonnative feature to be learned. However, studies on vision have demonstrated that perceptual learning may occur implicitly, by exposing learners to stimulus features, even if they are irrelevant to the task, and it has recently been suggested that this task irrelevant perceptual learning framework also applies to speech. In this study, subjects took part in a seven-day training regimen to learn to distinguish one of two nonnative features, namely, voice onset time or lexical tone, using explicit training methods consistent with most speech training studies. Critically, half of the subjects were exposed to stimuli that varied not only in the relevant feature, but in the irrelevant feature as well. The results showed that subjects who were trained with stimuli that varied in the relevant feature and held the irrelevant feature constant achieved the best learning outcomes. Varying both features hindered learning and generalization to new stimuli. PMID- 26827025 TI - Vocal imitations of basic auditory features. AB - Describing complex sounds with words is a difficult task. In fact, previous studies have shown that vocal imitations of sounds are more effective than verbal descriptions [Lemaitre and Rocchesso (2014). J. Acoust. Soc. Am. 135, 862-873]. The current study investigated how vocal imitations of sounds enable their recognition by studying how two expert and two lay participants reproduced four basic auditory features: pitch, tempo, sharpness, and onset. It used 4 sets of 16 referent sounds (modulated narrowband noises and pure tones), based on 1 feature or crossing 2 of the 4 features. Dissimilarity rating experiments and multidimensional scaling analyses confirmed that listeners could accurately perceive the four features composing the four sets of referent sounds. The four participants recorded vocal imitations of the four sets of sounds. Analyses identified three strategies: (1) Vocal imitations of pitch and tempo reproduced faithfully the absolute value of the feature; (2) Vocal imitations of sharpness transposed the feature into the participants' registers; (3) Vocal imitations of onsets categorized the continuum of onset values into two discrete morphological profiles. Overall, these results highlight that vocal imitations do not simply mimic the referent sounds, but seek to emphasize the characteristic features of the referent sounds within the constraints of human vocal production. PMID- 26827026 TI - Mandarin speech-in-noise and tone recognition using vocoder simulations of the temporal limits encoder for cochlear implants. AB - Temporal envelope-based signal processing strategies are widely used in cochlear implant (CI) systems. It is well recognized that the inability to convey temporal fine structure (TFS) in the stimuli limits CI users' performance, but it is still unclear how to effectively deliver the TFS. A strategy known as the temporal limits encoder (TLE), which employs an approach to derive the amplitude modulator to generate the stimuli coded in an interleaved-sampling strategy, has recently been proposed. The TLE modulator contains information related to the original temporal envelope and a slow-varying TFS from the band signal. In this paper, theoretical analyses are presented to demonstrate the superiority of TLE compared with two existing strategies, the clinically available continuous-interleaved sampling (CIS) strategy and the experimental harmonic-single-sideband-encoder strategy. Perceptual experiments with vocoder simulations in normal-hearing listeners are conducted to compare the performance of TLE and CIS on two tasks (i.e., Mandarin speech reception in babble noise and tone recognition in quiet). The performance of the TLE modulator is mostly better than (for most tone-band vocoders) or comparable to (for noise-band vocoders) the CIS modulator on both tasks. This work implies that there is some potential for improving the representation of TFS with CIs by using a TLE strategy. PMID- 26827027 TI - Measurement of acoustic particle motion in shallow water and its application to geoacoustic inversion. AB - Within an underwater acoustic waveguide, the interference among multipath arrivals causes a phase difference in orthogonal components of the particle velocity. When two components of the particle velocity are not in phase, the fluid particles follow an elliptical trajectory. This property of the acoustic field can be readily detected by a vector sensor. A non-dimensional vector quantity, the degree of circularity, is used to quantify how much the trajectory resembles a circle. In this paper, vector sensor measurements collected during the 2013 Target and Reverberation Experiment are used to demonstrate the effect of multipath interference on the degree of circularity. Finally, geoacoustic properties representing the sandy sediment at the experimental site are inverted by minimization of a cost function, which quantifies the deviation between the measured and modeled degree of circularity. PMID- 26827028 TI - The aero-acoustic Galbrun equation in the time domain with perfectly matched layer boundary conditions. AB - This paper presents a solution for aero-acoustic problems using the Galbrun equation in the time domain with a non-uniform steady mean flow in a two dimensional coordinate system and the perfectly matched layer technique as the boundary conditions corresponding to an unbounded domain. This approach is based on an Eulerian-Lagrangian description corresponding to a wave equation written only in terms of the Lagrangian perturbation of the displacement. It is an alternative to the Linearized Euler Equations for solving aero-acoustic problems. The Galbrun equation is solved using a mixed pressure-displacement Finite Element Method. A complex Laplace transform scheme is used to study the time dependent variables. Several numerical examples are presented to validate and illustrate the efficiency of the proposed approach. PMID- 26827029 TI - Effects of fluid medium flow and spatial temperature variation on acoustophoretic motion of microparticles in microfluidic channels. AB - A numerical modeling method for accurately predicting the acoustophoretic motion of compressible microparticles in microfluidic devices is presented to consider the effects of fluid medium flow and spatial temperature variation that can significantly influence the acoustophoretic motion. In the proposed method, zeroth-order fluid medium flow and temperature, and first- and second-order acoustic fields in the microfluidic devices are first calculated by applying quadratic mapping functions and a second-order finite difference method (FDM) to perturbed mass, momentum, and energy conservation equations and state equation. Then, the acoustic radiation force is obtained based on the Gorkov's acoustic radiation force equation and applied to the Newton's Equation of Motion to calculate the microparticle motion. The proposed method was validated by comparing its results to a commercial software package, COMSOL Multiphysics results, one-dimensional, analytical modeling results, and experimental results. It is shown that the fluid medium flow affects the acoustic radiation force and streaming significantly, resulting in the acoustic radiation force and streaming prediction errors of 10.9% and 67.4%, respectively, when the fluid medium flow speed is increased from 0 to 1 m/s. A local temperature elevation from 20 degrees C to 22 degrees C also results in the prediction errors of 88.4% and 73.4%. PMID- 26827030 TI - Modeling of aerodynamic interaction between vocal folds and vocal tract during production of a vowel-voiceless plosive-vowel sequence. AB - The context of this study is the physical modeling of speech production. The objective is, by using a mechanical replica of the vocal tract, to test quantitatively an aerodynamic model of the interaction between the vocal folds and the vocal tract during the production of a vowel-voiceless plosive-vowel sequence. The first step is to realize acoustic and aerodynamic measurements on a speaker during the production of an /apa/ sequence. The aperture and width of the lips are also derived from a high-speed video recording of the subject's face. Theoretical models to describe the flow through the lips and the effect of an expansion of the supraglottal cavity are proposed and validated by comparison with measurements made using a self-oscillating replica of the phonatory system. Finally, using these models, numerical simulations of an /apa/ sequence are performed using the measured lip parameters as the only time-varying input parameters. The results of these simulations suggest that the realization of an occlusion of the vocal tract produces a passive increase in glottal area associated with a voice offset and that the expansion of the supraglottal cavity is responsible for the extension of the phonation up to 40 ms after closure of the lips. PMID- 26827031 TI - An acoustic study of multiple lateral consonants in three Central Australian languages. AB - This study presents dental, alveolar, retroflex, and palatal lateral /ll l y/ data from three Central Australian languages: Arrernte, Pitjantjatjara, and Warlpiri. Formant results show that the laminal laterals (dental /l/ and palatal /y/) have a relatively low F1, presumably due to a high jaw position for these sounds, as well as higher F4. In addition, the palatal /y/ has very high F2. There is relatively little difference in F3 between the four lateral places of articulation. However, the retroflex /l/ appears to have slightly lower F3 and F4 in comparison to the other lateral sounds. Importantly, spectral moment analyses suggest that centre of gravity and standard deviation (first and second spectral moments) are sufficient to characterize the four places of articulation. The retroflex has a concentration of energy at slightly lower frequencies than the alveolar, while the palatal has a concentration of energy at higher frequencies. The dental is characterized by a more even spread of energy. These various results are discussed in light of different acoustic models of lateral production, and the possibility of spectral cues to place of articulation across manners of articulation is considered. PMID- 26827032 TI - Effects of relative and absolute frequency in the spectral weighting of loudness. AB - The loudness of broadband sound is often modeled as a linear sum of specific loudness across frequency bands. In contrast, recent studies using molecular psychophysical methods suggest that low and high frequency components contribute more to the overall loudness than mid frequencies. In a series of experiments, the contribution of individual components to the overall loudness of a tone complex was assessed using the molecular psychophysical method as well as a loudness matching task. The stimuli were two spectrally overlapping ten-tone complexes with two equivalent rectangular bandwidth spacing between the tones, making it possible to separate effects of relative and absolute frequency. The lowest frequency components of the "low-frequency" and the "high-frequency" complexes were 208 and 808 Hz, respectively. Perceptual-weights data showed emphasis on lowest and highest frequencies of both the complexes, suggesting spectral-edge related effects. Loudness matching data in the same listeners confirmed the greater contribution of low and high frequency components to the overall loudness of the ten-tone complexes. Masked detection thresholds of the individual components within the tone complex were not correlated with perceptual weights. The results show that perceptual weights provide reliable behavioral correlates of relative contributions of the individual frequency components to overall loudness of broadband sounds. PMID- 26827034 TI - Pitch and spectral resolution: A systematic comparison of bottom-up cues for top down repair of degraded speech. AB - The brain is capable of restoring missing parts of speech, a top-down repair mechanism that enhances speech understanding in noisy environments. This enhancement can be quantified using the phonemic restoration paradigm, i.e., the improvement in intelligibility when silent interruptions of interrupted speech are filled with noise. Benefit from top-down repair of speech differs between cochlear implant (CI) users and normal-hearing (NH) listeners. This difference could be due to poorer spectral resolution and/or weaker pitch cues inherent to CI transmitted speech. In CIs, those two degradations cannot be teased apart because spectral degradation leads to weaker pitch representation. A vocoding method was developed to evaluate independently the roles of pitch and spectral resolution for restoration in NH individuals. Sentences were resynthesized with different spectral resolutions and with either retaining the original pitch cues or discarding them all. The addition of pitch significantly improved restoration only at six-bands spectral resolution. However, overall intelligibility of interrupted speech was improved both with the addition of pitch and with the increase in spectral resolution. This improvement may be due to better discrimination of speech segments from the filler noise, better grouping of speech segments together, and/or better bottom-up cues available in the speech segments. PMID- 26827035 TI - Temporal weighting of loudness: Comparison between two different psychophysical tasks. AB - Psychophysical studies on loudness have so far examined the temporal weighting of loudness solely in level-discrimination tasks. Typically, listeners were asked to discriminate hundreds of level-fluctuating sounds regarding their global loudness. Temporal weights, i.e., the importance of each temporal portion of the stimuli for the loudness judgment, were then estimated from listeners' responses. Consistent non-uniform "u-shaped" temporal weighting patterns were observed, with greater weights assigned to the first and the last temporal portions of the stimuli, revealing significant primacy and recency effects, respectively. In this study, the question was addressed whether the same weighting pattern could be found in a traditional loudness estimation task. Temporal loudness weights were compared between a level-discrimination (LD) task and an absolute magnitude estimation (AME) task. Stimuli were 3-s broadband noises consisting of 250-ms segments randomly varying in level. Listeners were asked to evaluate the global loudness of the stimuli by classifying them as "loud" or "soft" (LD), or by assigning a number representing their loudness (AME). Results showed non-uniform temporal weighting in both tasks, but also significant differences between the two tasks. An explanation based on the difference in complexity between the evaluation processes underlying each task is proposed. PMID- 26827036 TI - Performance metrics for depth-based signal separation using deep vertical line arrays. AB - A recent publication by McCargar and Zurk [(2013). J. Acoust. Soc. Am. 133(4), EL320-EL325] introduced a modified Fourier transform-based method for passive source depth estimation using vertical line arrays deployed below the critical depth in the deep ocean. This method utilizes the depth-dependent modulation caused by the interference between the direct and surface-reflected acoustic arrivals, the observation of which is enhanced by propagation through the reliable acoustic path. However, neither the performance of this method nor its limits of applicability have yet been thoroughly investigated. This paper addresses both of these issues; the first by identifying and analyzing the factors that influence the resolution and ambiguity in the transform-based depth estimate; the second by introducing another, much simpler depth estimation method, which is used to determine the target trajectories required for observation of the interference pattern and the array requirements for accurate depth estimation. PMID- 26827037 TI - Relationship between tongue positions and formant frequencies in female speakers. AB - This study examined the relationship (1) between acoustic vowel space and the corresponding tongue kinematic vowel space and (2) between formant frequencies (F1 and F2) and tongue x-y coordinates for the same time sampling point. Thirteen healthy female adults participated in this study. Electromagnetic articulography and synchronized acoustic recordings were utilized to obtain vowel acoustic and tongue kinematic data across ten speech tasks. Intra-speaker analyses showed that for 10 of the 13 speakers the acoustic vowel space was moderately to highly correlated with tongue kinematic vowel space; much weaker correlations were obtained for inter-speaker analyses. Correlations of individual formants with tongue positions showed that F1 varied strongly with tongue position variations in the y dimension, whereas F2 was correlated in equal magnitude with variations in the x and y positions. For within-speaker analyses, the size of the acoustic vowel space is likely to provide a reasonable inference of size of the tongue working space for most speakers; unfortunately there is no a priori, obvious way to identify the speakers for whom the covariation is not significant. A second conclusion is that F1 variations reflect tongue height, but F2 is a much more complex reflection of tongue variation in both dimensions. PMID- 26827038 TI - A study on transvelar coupling for non-nasalized sounds. AB - Previous studies have found that the velum in speech production may not only serve as a binary switch with on-off states for nasal and non-nasal sounds, but also partially alter the acoustic characteristics of non-nasalized sounds. The present study investigated the unique functions of the velum in the production of non-nasalized sounds by using morphological, mechanical, and acoustical measurements. Magnetic resonance imaging movies obtained from three Japanese speakers were used to measure the behaviors of the velum and dynamic changes in the pseudo-volume of the pharyngeal cavity during utterances of voiced stops and vowels. The measurements revealed no significant enlargements in the supraglottal cavity as subjects uttered voiced stops. It is found that the velum thickness varied across utterances in a way that depended on vowels, but not on consonants. The mechanical and acoustical observations in the study suggested that the velum is actively controlled to augment the voice bars of voiced stops, and nostril radiated sound is one of the most important sources for voice bars, just as is laryngeal wall vibration. This study also proposed a two-layer diaphragm model that simulates transvelar coupling during the production of non-nasalized speech sounds. The simulation demonstrated that the model accurately represented the basic velar functions involved in speech production. PMID- 26827039 TI - The intelligibility of interrupted and temporally altered speech: Effects of context, age, and hearing loss. AB - Temporal constraints on the perception of interrupted speech were investigated by comparing the intelligibility of speech that was periodically gated (PG) and subsequently either temporally compressed (PGTC) by concatenating remaining speech fragments or temporally expanded (PGTE) by doubling the silent intervals between speech fragments. Experiment 1 examined the effects of PGTC and PGTE at different gating rates (0.5 -16 Hz) on the intelligibility of words and sentences for young normal-hearing adults. In experiment 2, older normal-hearing (ONH) and older hearing-impaired (OHI) adults were tested with sentences only. The results of experiment 1 indicated that sentences were more intelligible than words. In both experiments, PGTC sentences were less intelligible than either PG or PGTE sentences. Compared with PG sentences, the intelligibility of PGTE sentences was significantly reduced by the same amount for ONH and OHI groups. Temporal alterations tended to produce a U-shaped rate-intelligibility function with a dip at 2-4 Hz, indicating that temporal alterations interacted with the duration of speech fragments. The present findings demonstrate that both aging and hearing loss negatively affect the overall intelligibility of interrupted and temporally altered speech. However, a mild-to-moderate hearing loss did not exacerbate the negative effects of temporal alterations associated with aging. PMID- 26827040 TI - The effect of presentation level on spectral weights for sentences. AB - Psychophysical data indicate that spectral weights tend to increase with increasing presentation level at high frequencies. The present study examined whether spectral weights for speech perception are similarly affected by presentation level. Stimuli were sentences filtered into five contiguous frequency bands and presented at each of two levels (75 and 95 dB sound pressure level [SPL]). For the highest band (2807-10,000 Hz), normal-hearing listeners' weights were higher for the higher presentation level. Weights for the 95-dB-SPL level resembled those previously estimated for hearing-impaired listeners tested at comparably high levels, suggesting that hearing loss itself may not play a large role in spectral weighting for a sentence recognition task. PMID- 26827041 TI - A fast and stable solver for acoustic scattering problems based on the nonuniform grid approach. AB - A fast and stable boundary element method (BEM) algorithm for solving external problems of acoustic scattering by impenetrable bodies is developed. The method employs the Burton-Miller integral equation, which provides stable convergence of iterative solvers, and a generalized multilevel nonuniform grid (MLNG) algorithm for fast evaluation of field integrals. The MLNG approach is used here for the removal of computational bottlenecks involved with repeated matrix-vector multiplications as well as for the low-order basis function regularization of the hyper-singular integral kernel. The method is used for calculating the fields scattered by large acoustic scatterers, including nonconvex bodies with piece wise smooth surfaces. As a result, the algorithm is capable of accurately incorporating high-frequency effects such as creeping waves and multiple-edges diffractions. In all cases, stable convergence of the method is observed. High accuracy of the method is demonstrated by comparison with the traditional BEM solution. The computational complexity of the method in terms of both the computation time and storage is estimated in practical computations and shown to be close to the asymptotic O(N log N) dependence. PMID- 26827043 TI - Is low frequency ocean sound increasing globally? AB - Low frequency sound has increased in the Northeast Pacific Ocean over the past 60 yr [Ross (1993) Acoust. Bull. 18, 5-8; (2005) IEEE J. Ocean. Eng. 30, 257-261; Andrew, Howe, Mercer, and Dzieciuch (2002) J. Acoust. Soc. Am. 129, 642-651; McDonald, Hildebrand, and Wiggins (2006) J. Acoust. Soc. Am. 120, 711-717; Chapman and Price (2011) J. Acoust. Soc. Am. 129, EL161-EL165] and in the Indian Ocean over the past decade, [Miksis-Olds, Bradley, and Niu (2013) J. Acoust. Soc. Am. 134, 3464-3475]. More recently, Andrew, Howe, and Mercer's [(2011) J. Acoust. Soc. Am. 129, 642-651] observations in the Northeast Pacific show a level or slightly decreasing trend in low frequency noise. It remains unclear what the low frequency trends are in other regions of the world. In this work, data from the Comprehensive Nuclear-Test Ban Treaty Organization International Monitoring System was used to examine the rate and magnitude of change in low frequency sound (5-115 Hz) over the past decade in the South Atlantic and Equatorial Pacific Oceans. The dominant source observed in the South Atlantic was seismic air gun signals, while shipping and biologic sources contributed more to the acoustic environment at the Equatorial Pacific location. Sound levels over the past 5-6 yr in the Equatorial Pacific have decreased. Decreases were also observed in the ambient sound floor in the South Atlantic Ocean. Based on these observations, it does not appear that low frequency sound levels are increasing globally. PMID- 26827042 TI - Automatic detection of Parkinson's disease in running speech spoken in three different languages. AB - The aim of this study is the analysis of continuous speech signals of people with Parkinson's disease (PD) considering recordings in different languages (Spanish, German, and Czech). A method for the characterization of the speech signals, based on the automatic segmentation of utterances into voiced and unvoiced frames, is addressed here. The energy content of the unvoiced sounds is modeled using 12 Mel-frequency cepstral coefficients and 25 bands scaled according to the Bark scale. Four speech tasks comprising isolated words, rapid repetition of the syllables /pa/-/ta/-/ka/, sentences, and read texts are evaluated. The method proves to be more accurate than classical approaches in the automatic classification of speech of people with PD and healthy controls. The accuracies range from 85% to 99% depending on the language and the speech task. Cross language experiments are also performed confirming the robustness and generalization capability of the method, with accuracies ranging from 60% to 99%. This work comprises a step forward for the development of computer aided tools for the automatic assessment of dysarthric speech signals in multiple languages. PMID- 26827044 TI - Speed of sound in diseased liver observed by scanning acoustic microscopy with 80 MHz and 250 MHz. AB - In this study, the speed of sound (SOS) of two types of rat livers (eight normal livers, four cirrhotic livers) was measured with a scanning acoustic microscope using two transducers, one of which had an 80-MHz and the other a 250-MHz center frequency. The 250-MHz transducer had a better spatial resolution adapted to studying fiber or hepatic parenchymal cells. In normal livers, averages of the SOS values were from 1598 to 1677 m/s at 80-MHz and from 1568 to 1668 m/s at 250 MHz. In the fiber tissue of cirrhotic livers, averages of the SOS values were from 1645 to 1658 m/s at 80-MHz and from 1610 to 1695 m/s at 250-MHz, while the SOS values in the other tissue of cirrhotic livers ranged from 1644 to 1709 m/s at 80-MHz and from 1641 to 1715 m/s at 250-MHz. In one liver, SOS in fiber tissue was larger than that of tissues without fiber while in others it was lower. The resulting two-dimensional SOS maps provide a unique quantitative insight of liver acoustic microstructures in a healthy liver and in a cirrhotic ones. This study would be helpful to understand the complex relationship between acoustic properties and liver disease including fiber tissue. PMID- 26827045 TI - The sound insulation of single leaf finite size rectangular plywood panels with orthotropic frequency dependent bending stiffness. AB - Current theories for predicting the sound insulation of orthotropic materials are limited to a small range of infinite panels. This paper presents a method that allows for the prediction of the sound insulation of a finite size orthotropic panel. This method uses an equation for the forced radiation impedance of a finite size rectangular panel. This approach produces an equation that has three nested integrals. The long numerical calculation times were reduced by using approximate formulas for the azimuthally averaged forced radiation impedance. This reduced the number of nested integrals from three to two. The resulting predictions are compared to results measured using two sample sizes of four different thicknesses of plywood and one sample size of another three different thicknesses of plywood. Plywood was used for all the tests because it is somewhat orthotropic. It was found during testing that the Young's moduli of the plywood were dependent on the frequency of excitation. The influence of the frequency dependent Young's moduli was then included in the prediction method. The experimental results were also compared with a simple isotropic prediction method. PMID- 26827046 TI - Hypersingular meshless method using double-layer potentials for three-dimensional exterior acoustic problems. AB - Three-dimensional exterior acoustic problems with irregular domains are solved using a hypersingular meshless method. In particular, the method of fundamental solutions (MFS) is used to formulate and analyze such acoustic problems. It is well known that source points for MFS cannot be located on the real boundary due to the singularity of the kernel functions. Thus, the diagonal terms of the influence matrices are unobtainable when source points are located on the boundary. An efficient approach is proposed to overcome such difficulties, when the MFS is used for three-dimensional exterior acoustic problems. This work is an extension of previous research on two-dimensional problems. The solution of the problem is expressed in terms of a double-layer potential representation on the physical boundary. Three examples are presented in which the proposed method is compared to the MFS and boundary element method. Good numerical performance is demonstrated by the proposed hypersingular meshless method. PMID- 26827049 TI - Local propagation speed constrained estimation of the slowness vector from non planar array observations. AB - The estimation of the slowness vector of infrasound waves propagating across an array is a critical process leading to the determination of parameters of interest such as the direction of arrival. The sensors of an array are often considered to be located in a horizontal plane. However, due to topography, the altitudes of the sensors are not identical and introduce a bias on the estimate if neglected. However, the unbiased 3D estimation procedure, while suppressing the bias, leads to an increase of the variance. Accounting for an a priori constraint on the slowness vector significantly reduces the variance and could therefore improve the performance of the estimation if the introduced bias by incorrect a priori information remains negligible. This study focuses on measuring the benefits of this approach with a thorough investigation of the bias and variance of the constrained 3D estimator, which is not available in the existing literature. This contribution provides such computations based on an asymptotic Gaussian approximation. Simulations are carried out to assess the theoretical results both with synthetic and real data. Thus, a constrained 3D estimator is proposed yielding the best bias/variance compromise if good knowledge of the propagation wave speed is accessible. PMID- 26827050 TI - An examination of the different ways that non-native phones may be perceptually assimilated as uncategorized. AB - This study examined three ways that perception of non-native phones may be uncategorized relative to native (L1) categories: focalized (predominantly similar to a single L1 category), clustered (similar to > 2 L1 categories), and dispersed (not similar to any L1 categories). In an online study, Egyptian Arabic speakers residing in Egypt categorized and rated all Australian English vowels. Evidence was found to support focalized, clustered, and dispersed uncategorized assimilations. Second-language (L2) category formation for uncategorized assimilations is predicted to depend upon the degree of perceptual overlap between the sets of L1 categories listeners use in assimilating each phone within an L2 contrast. PMID- 26827051 TI - Reading ability influences native and non-native voice recognition, even for unimpaired readers. AB - Research suggests that phonological ability exerts a gradient influence on talker identification, including evidence that adults and children with reading disability show impaired talker recognition for native and non-native languages. The present study examined whether this relationship is also observed among unimpaired readers. Learning rate and generalization of learning in a talker identification task were examined in average and advanced readers who were tested in both native and non-native language conditions. The results indicate that even among unimpaired readers, phonological competence as captured by reading ability exerts a gradient influence on perceptual learning for talkers' voices. PMID- 26827052 TI - How do outcomes compare between women and men living with HIV in Australia? An observational study. AB - Background Gender differences vary across geographical settings and are poorly reported in the literature. The aim of this study was to evaluate demographics and clinical characteristics of participants from the Australian HIV Observational Database (AHOD), and to explore any differences between females and males in the rate of new clinical outcomes, as well as initial immunological and virological response to antiretroviral therapy. METHODS: Time to a new clinical end-point, all-cause mortality and/or AIDS illness was analysed using standard survival methods. Univariate and covariate adjusted Cox proportional hazard models were used to evaluate the time to plasma viral load suppression in all patients that initiated antiretroviral therapy (ART) and time to switching from a first-line ART to a second-line ART regimen. RESULTS: There was no significant difference between females and males for the hazard of all-cause mortality [adjusted hazard ratio: 0.98 (0.51, 1.55), P=0.67], new AIDS illness [adjusted hazard ratio: 0.75 (0.38, 1.48), P=0.41] or a composite end-point [adjusted hazard ratio: 0.74 (0.45, 1.21), P=0.23]. Incident rates of all-cause mortality were similar between females and males; 1.14 (0.61, 1.95) vs 1.28 (1.12, 1.45) per 100 person years. Virological response to ART was similar for females and males when measured as time to viral suppression and/or time to virological failure. CONCLUSION: This study supports current Australian HIV clinical care as providing equivalent standards of care for male and female HIV-positive patients. Future studies should compare ART-associated toxicity differences between ART associated toxicity differences between men and women living with HIV in Australia. PMID- 26827053 TI - Types of abuse and risk factors associated with elder abuse. AB - PRINCIPLES: Detecting elder abuse is challenging because it is a taboo, and many cases remain unreported. This study aimed to identify types of elder abuse and to investigate its associated risk factors. METHODS: Retrospective analyses of 903 dossiers created at an Independent Complaints Authority for Old Age in the Canton of Zurich, Switzerland, from January 1, 2008 to October 31, 2012. Characteristics of victims and perpetrators, types of abuse, and associated risk factors related to the victim or the perpetrator were assessed. Bi- and multivariate analysis were used to identify abuse and neglect determinants. RESULTS: A total of 150 cases reflected at least one form of elder abuse or neglect; 104 cases were categorised as abuse with at least one type of abuse (overall 135 mentions), 46 cases were categorised as neglect (active or passive). Psychological abuse was the most reported form (47%), followed by financial (35%), physical (30%) and anticonstitutional abuse (18%). In 81% of the 150 cases at least two risk factors existed. In 13% no associated risk factor could be identified. Compared with neglect, elders with abuse were less likely to be a nursing home resident than living at home (odds ratio [OR] 0.02, 95% confidence interval [CI] 0.00-0.19). In addition, they were more likely to be cohabiting with their perpetrators (OR 18.01, 95% CI 4.43-73.19). CONCLUSION: For the majority of the reported elder abuse cases at least two associated risk factors could be identified. Knowledge about these red flags and a multifaceted strategy are needed to identify and prevent elder abuse. PMID- 26827054 TI - Non surgical predicting factors for patient satisfaction after third molar surgery. AB - BACKGROUND: In the third molar surgery, it is important to focus not only on surgical skills, but also on patient satisfaction. Classically studies have been focused on surgery and surgeon's empathy, but there are non-surgical factors that may influence patient satisfaction. MATERIAL AND METHODS: A cross-sectional study was performed on 100 patients undergoing surgical extractions of impacted mandibular third molars treated from October 2013 to July 2014 in the Oral Surgery Unit of the University of Valencia. A questionnaire (20 questions) with a 10-point Likert scale was provided. The questionnaire assessed the ease to find the center, the ease to get oriented within the center, the burocratic procedures, the time from the first visit to the date of surgical intervention, waiting time in the waiting room, the comfort at the waiting room, the administrative staff (kindness and efficiency to solve formalities), medical staff (kindness, efficiency, reliability, dedication), personal data care, clarity in the information received (about the surgery, postoperative care and resolution of the doubts), available means and state of facilities. Outcome variables were overall satisfaction and recommendation of the center. Statistical analysis was made using the multiple linear regression analysis. RESULTS: Significant correlations were found between all variables and overall satisfaction. The multiple regression model showed that the efficiency of the surgeon and the clarity of the information were statistically significant to overall satisfaction and recommendation of the center. The kindness of the administrative staff, available means, the state of facilities and the comfort at the waiting room were statistically significant to the recommendation of the center. CONCLUSIONS: Patient satisfaction directly depends on the efficiency of the surgeon and clarity of the clinical information received about the procedure. Appreciation of these predictive factors may help clinicians to provide optimal care for impacted third molar surgery patients. PMID- 26827055 TI - Vascular mapping of the face: B-mode and doppler ultrasonography study. AB - BACKGROUND: To analyze the face vascularization pattern using B-mode and Doppler ultrasonography, and also propose an arterial vessel mapping. MATERIAL AND METHODS: The investigation was performed on 20 ultrasonography exams of facial vessels through linear and endocavitary transducers. We analyzed and determined the average values for diameters, peak systolic velocity and resistive index of the following arteries: external carotid, lingual, deep lingual, sublingual, facial, submental, inferior labial, superior labial, angular, maxillary inferior alveolar, mental, buccal, greater palatine, infraorbital, superficial temporal, transverse facial and frontal. RESULTS: Data was obtained allowing the analysis of the tissue hemodynamics. We were able to map the vascularization of the face and it was possible to access three arteries of small diameter (0,60mm angular artery; 0,55mm greater palatine artery; 0,45mm infraorbital artery). CONCLUSIONS: The results presented in this article are valid tool supporting the non-invasive mapping of facial vascularization. PMID- 26827056 TI - Dental research in Spain. A bibliometric analysis on subjects, authors and institutions (1993-2012). AB - BACKGROUND: Bibliometrics is defined as the use of statistical methods in the analysis of a body of literature to reveal the historical development of subject fields and patterns of authorship, publication, and use. Our objective was to characterize Spanish scientific output in Dentistry through the analysis of Web of Science database in a 20-year period. By means of a bibliometric study documents were statistically analyzed using indicators that showed quantitative and qualitative aspects of the production. Specifically, time course of the scientific production within the time span was analysed, as were the journals where the article was published and the categories of Journal Citation Reports (JCR) in which they belong, thematic areas, authorship, and finally authors and institutions with the highest production in Spain. MATERIAL AND METHODS: By means of the design of a specific search strategy previously described in the scientific literature, we recovered all citable documents about Dentistry signed by Spanish researchers and included in the WoS database between 1993 and 2012. RESULTS: A total of 3006 documents fulfilled the search criteria, of which 2449 (81.5%) were published in journals within the category Dentistry Oral Surgery and Medicine and 557 (18.5%) within other categories of the JCR. During the four quinquenniums studied, the production increased quantitatively (8.6-fold) and qualitatively. Finally, the universities of Granada and Complutense of Madrid were the institutions with the highest production and most prolific authors. CONCLUSIONS: The Spanish dental production sharply increased in the last two decades, reaching quantitative and qualitative levels similar to those of the other medical specialties in the country. PMID- 26827057 TI - Clinical findings and risk factors to oral squamous cell carcinoma in young patients: A 12-year retrospective analysis. AB - BACKGROUND: In recent years have been observed an increased incidence of OSCC in young individuals. Based on this, the aim this study was to describe the clinical characteristics of all cases of OSCC in younger patients, diagnosed in two oncology referral hospitals, at the northeast region of Brazil within a 12-year period. MATERIAL AND METHODS: Data regarding general characteristics of patients (age, gender and tobacco and/or alcohol habits) and information about the lesions (tumor location, size, regional lymph node metastasis, distant metastasis and clinical stage) were submitted to descriptive and inferential analysis. Statistical analysis included Chi-square and Fisher's exact tests (P<0.05). RESULTS: Out of 2311 registered cases of OSCC, 76 (3.3%) corresponded to OSCC in patients under 45 years old. Most of them were male (n=62, 81.6%) and tobacco and/or alcohol users (n=40, 52.8%). The most frequent site was the tongue (n=31, 40.8%), with predominance of cases classified at advanced clinical stage (III and IV, n = 46, 60.5%). The advanced stage of OSCC (III and IV) was statistically associated with male gender (P=0.035), lower education level (P=0.007), intraoral sites (P<0.001), presence of pain symptomatology (P=0.006), and consumption of tobacco and/or alcohol (P=0.001). CONCLUSIONS: The profile of OSCC in young patients resembles to the commonly characteristics reported for overall population. The late diagnosis in young patients usually results in poor prognosis, associated with gender, harmful habits and tumor location. Although prevalence is low, stimulus to prevention and to early diagnosis should be addressed to young individuals exposed to risk factors. PMID- 26827058 TI - Prevalence of salivary Epstein-Barr virus in potentially malignant oral disorders and oral squamous cell carcinoma. AB - BACKGROUND: To analyze the presence of salivary Epstein-Barr virus (EBV) DNA in oral squamous cell carcinoma and potentially malignant oral disorders. MATERIAL AND METHODS: Three groups were studied: Group 1 (12 oral squamous cell carcinomas (OSCC)), Group 2 (12 potentially malignant oral disorders (PMD)) and Group 3 (47 healthy controls). EBV DNA salivary analysis was performed by PCR. RESULTS: The highest percentage of positive salivary EBV DNA corresponded to the OSCC group (58.3%), followed by the PMD group (41.7%) and the controls (40.4%). The differences between groups were not statistically significant, however (p>0.05). CONCLUSIONS: Salivary EBV DNA was more prevalent in OSCC than in PMD or the controls. PMID- 26827059 TI - Lack of evidence of hepatitis in patients with oral lichen planus in China: A case control study. AB - BACKGROUND: China has been one of the countries with high prevalence of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) liver disease. And lichen planus is an extrahepatic manifestation of patients with chronic HCV infection. This case-control study was conducted to investigate the relationship between oral lichen planus (OLP) and HBV/HCV infection in China. MATERIAL AND METHODS: A total of 776 patients, including 150 patients with OLP (Group OLP), 429 inpatients from the Trauma Ward of Oral and Maxillofacial Surgery Department (Group A), 110 patients with other oral mucosal diseases, but without a reported association with HCV infection (Group B) and 87 patients with oral lichenoid lesion (Group OLL), were compared with their seroprevalence of anti-HCV antibody (HCVAb), hepatitis B surface antigen (HBsAg) and the parameters of liver functions. Moreover, the clinical characteristics of OLP were also observed, such as gender, age, chief complaint, course of the disease, clinical type, sites involved and so on. RESULTS: The positive rates of HCVAb and HBsAg in OLP patients were 0.7% and 4%, respectively. Neither HCVAb nor HBsAg was associated with OLP as demonstrated by both the univariate and the multivariate analyses. The clinical features and liver functions of OLP patients with negative or positive HBsAg were nearly the same. CONCLUSIONS: Our findings verify that there is no association between OLP and hepatitis and there is no need to run a screening test for HCV or HBV in OLP patients in China. PMID- 26827060 TI - Impact of oral mucosa lesions on the quality of life related to oral health. An etiopathogenic study. AB - BACKGROUND: To assess the impact of oral mucosa lesions on quality of life related to oral health (QLROH) and additionally to establish whether the etiopathogenicy of oral lesion is associated to the degree of QLROH impact. MATERIAL AND METHODS: In this cross-sectional study performed on a non probability sample of 247 consecutively patients attending the oral medicine and pathology clinic the Spanish version of Oral Health Impact Profile-49 questionnaire (OHIP-49-mx) was applied. Responses were recorded on Likert-type scale whose values ranged from 0 (never) to 4 (always). Values greater than the 50 percentile (median) were considered as indicative of poor quality of life. All patients were orally examined and diagnosed. In accordance to their etiopathogenicy 6 study groups were formed: 4 corresponded to MIND classification for diseases (Metabolic, Inflammatory, Neoplastic, and Development groups), with >=2 diseases and no-lesion group. To identify possible differences of OHIP-49 values between study groups an ANOVA (one factor) parametric and a chi square tests were performed (SPSS(r)20.0). RESULTS: The OHIP-49-mx values were higher than the 50 percentile (established at 39) in metabolic, inflammatory, development, and >=2 diseases groups, suggesting that this type of oral lesions negatively impact the quality of life. >=2 diseasesgroup followed by metabolic and inflammatory diseases group (p 0.001) depicted worst quality of life. Functional limitation (p 0.003), pain, physical inability (p 0.001) and psychological disabilities dimensions exhibited greater values in all groups. CONCLUSIONS: Injured oral mucosa negatively impacts quality of life, specifically functional limitation, physical inability and psychological disabilities could lead to social isolation.To our knowledge, this is the first time that an association between QLROH and the etiopathogenicy of oral mucosal diseases is established. PMID- 26827061 TI - Recurrent aphthous stomatitis and Helicobacter pylori. AB - BACKGROUND: Recurrent aphthous stomatitis (RAS) is a recurrent painful ulcerative disorder that commonly affects the oral mucosa. Local and systemic factors such as trauma, food sensitivity, nutritional deficiencies, systemic conditions, immunological disorders and genetic polymorphisms are associated with the development of the disease. Helicobacter pylori (H. pylori) is a gram-negative, microaerophile bacteria, that colonizes the gastric mucosa and it was previously suggested to be involved in RAS development. In the present paper we reviewed all previous studies that investigated the association between RAS and H. pylori. MATERIAL AND METHODS: A search in Pubmed (MEDLINE) databases was made of articles published up until July 2015 using the following keywords: Helicobacter Pylori or H. pylori and RAS or Recurrent aphthous stomatitis. RESULTS: Fifteen experimental studies that addressed the relationship between infection with H. pylori and the presence of RAS and three reviews, including a systematic review and a meta analysis were included in this review. The studies reviewed used different methods to assess this relationship, including PCR, nested PCR, culture, ELISA and urea breath test. A large variation in the number of patients included in each study, as well as inclusion criteria and laboratorial methods was observed. H. pylori can be detected in the oral mucosa or ulcerated lesion of some patients with RAS. The quality of the all studies included in this review was assessed using levels of evidence based on the University of Oxford's Center for Evidence Based Medicine Criteria. CONCLUSIONS: Although the eradication of the infection may affect the clinical course of the oral lesions by undetermined mechanisms, RAS ulcers are not associated with the presence of the bacteria in the oral cavity and there is no evidence that H. pylori infection drives RAS development. PMID- 26827062 TI - Bisphosphonates, vitamin D, parathyroid hormone, and osteonecrosis of the jaw. Could there be a missing link? AB - BACKGROUND: It is estimated that over 190 million bisphosphonates have been prescribed worldwide. But this drug can produce adverse effects, of which osteonecrosis of the jaw and severe hypocalcemia are the most serious. It is evident that bisphosphonate administration affects multiple and diverse biochemical mediators related to bone metabolism. MATERIAL AND METHODS: This review of literature investigates four basic parameters in patients treated with bisphosphonates - parathyroid hormone (PTH), bisphosphonates, vitamin D, calcium, and jaw osteonecrosis - which are fundamental for assessing bone metabolism and so the efficacy and correct use of the drug. The imbalances generated by vitamin D and calcium deficiencies, together with their multiple systemic repercussions, have been widely researched but the outcomes of these imbalances in relation to bisphosphonate administration are not well known, and some research has indicated that they may be associated with osteonecrosis of the jaw (ONJ). RESULTS: The present review set out to explain the functioning of bone metabolism, the importance of different chemical mediators, the imbalances produced by incorrect use of this drug, in order to forewarn against the possible relation of these parameters with ONJ, whose physiopathology remains unknown. CONCLUSIONS: Medical and dental clinics should keep detailed anamneses of the use of vitamin D and calcium supplements, as it is of vital importance to maintain their correct levels in blood, given that these are related to ONJ as well as other adverse effects; this procedure is also necessary in order to ensure the correct use of the drug. PMID- 26827063 TI - Complications in the use of the mandibular body, ramus and symphysis as donor sites in bone graft surgery. A systematic review. AB - BACKGROUND: To develop a systematic review by assessing and comparing the different complications that occurs in bone graft surgery using the mandibular body, ramus and symphysis as donor sites. MATERIAL AND METHODS: In order to respond to the following question, a systematic review was developed: does the use of intraoral mandibular body and ramus as donor sites in bone graft surgery, produce fewer and less severe complications in comparison to the use of the mandibular symphysis in patients that present bone resorption that needs augmentation using autologous grafts? The review was carried out between January 1990 and 2015, during which only clinical essays with a minimum follow-up period of six months were included. RESULTS: The initial search yielded a total of 2912 articles, of which 6 were finally selected. In total, 259 graft surgeries were performed; 118 using the mandibular body and ramus as donor sites, and 141, the symphysis. The most frequent complications that arose when using the mandibular symphysis were temporary sensory alterations in the anterior teeth (33.87%), followed by sensory alterations of the skin and mucosa (18.57%). As for the mandibular body and ramus donor sites, the most frequent complications relate to temporary sensory alterations of the mucosa (8.19%) and to minor postoperative bleeding (6.55%). CONCLUSIONS: The analyzed results show a higher prevalence and severity of complications when using mandibular symphysis bone grafts, producing more discomfort for the patient. Therefore, it would be advisable to perform further clinical essays due to the lack of studies found. PMID- 26827064 TI - Surface characterization and in vivo evaluation of laser sintered and machined implants followed by resorbable-blasting media process: A study in sheep. AB - BACKGROUND: This study aimed to compare the histomorphometric and histological bone response to laser-sintered implants followed by resorbable-blasting media (RBM) process relative to standard machined/RBM surface treated implants. MATERIAL AND METHODS: Six male sheep (n=6) received 2 Ti-6Al-4V implants (1 per surface) in each side of the mandible for 6 weeks in vivo. The histomorphometric parameters bone-implant contact (BIC) and bone area fraction occupancy (BAFO) were evaluated. RESULTS: Optical interferometry revealed higher Sa and Sq values for the laser-sintered/RBM surface in relation to standard/RBM implants. No significant differences in BIC were observed between the two groups (p>0.2), but significantly higher BAFO was observed for standard/RBM implants (p<0.01). CONCLUSIONS: The present study demonstrated that both surfaces were biocompatible and osseoconductive, and the combination of laser sintering and RBM has no advantage over the standard machined implants with subsequent RBM. PMID- 26827065 TI - Prevention of medication-related osteonecrosis of the jaws secondary to tooth extractions. A systematic review. AB - BACKGROUND: A study was made to identify the most effective protocol for reducing the risk of osteonecrosis of the jaws (ONJ) following tooth extraction in patients subjected to treatment with antiresorptive or antiangiogenic drugs. MATERIAL AND METHODS: A MEDLINE and SCOPUS search (January 2003 - March 2015) was made with the purpose of conducting a systematic literature review based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. All articles contributing information on tooth extractions in patients treated with oral or intravenous antiresorptive or antiangiogenic drugs were included. RESULTS: Only 13 of the 380 selected articles were finally included in the review: 11 and 5 of them offered data on patients treated with intravenous and oral bisphosphonates, respectively. No randomized controlled trials were found - all publications corresponding to case series or cohort studies. The prevalence of ONJ in the patients treated with intravenous and oral bisphosphonates was 6,9% (range 0-34.7%) and 0.47% (range 0-2.5%), respectively. The main preventive measures comprised local and systemic infection control. CONCLUSIONS: No conclusive scientific evidence is available to date on the efficacy of ONJ prevention protocols in patients treated with antiresorptive or antiangiogenic drugs subjected to tooth extraction. PMID- 26827066 TI - Concept, diagnosis and classification of bisphosphonate-associated osteonecrosis of the jaws. A review of the literature. AB - BACKGROUND: Bisphosphonates (BPs) and other antiresorptive agents such as denosumab are widely prescribed for the treatment of osteoporosis and are also used in patients with multiple myeloma and metastatic breast or prostate cancer for avoiding bone reabsorption and fractures that result in increased morbidity mortality among such individuals. MATERIAL AND METHODS: We made a bibliographic search to analyze the concept, diagnosis and the different classifications for bisphosphonate-associated osteonecrosis of the jaws. RESULTS: Osteonecrosis of the jaws (ONJ) is an important complication of exposure to BPs or other antiresorptive agents, and although its prevalence is low, it can pose management problems. The definition, diagnosis and classification of osteonecrosis have evolved since Marx reported the first cases in 2003. CONCLUSIONS: The present study offers a literature review and update on the existing diagnostic methods and classification of the disorder, with a view to facilitating earlier and more effective treatment. PMID- 26827079 TI - Ethical decision-making and patients' beliefs. PMID- 26827072 TI - Letter to the Editor: Use of some inappropriate terms in Spanish in Oral Medicine and Pathology. PMID- 26827076 TI - Primary progressive multiple sclerosis--why we are failing. PMID- 26827075 TI - Oil prices, climate change--health challenges in Saudi Arabia. PMID- 26827067 TI - Effect of implant macro-design on primary stability: A prospective clinical study. AB - BACKGROUND: Implant restorations have become a high predictable treatment option. Several caracteristics such as surgical technique and implant design can influence the treatment outcomes. The aim of the present study was to evaluate the influence of implant macro-design on primary stability measured with resonance frequency analysis (RFA) and insertion torque (IT). Material and Mehods: A total of 47 implants divided in two groups: Test group (TI): 22 Tapered MIS(r) Seven implants; Control group (CI): 25 cylindrical Astra(r) Osseospeed implants. All implants were inserted following the manufacturers' standard protocols. Implant primary stability was measured at the moment of implant placement by registering insertion torque values (ITv) and ISQ values by means of OsstellTM Mentor (ISQv) (Integration Diagnostic Ltd., Goteborg, Sweden). RESULTS: In the mandible, mean ISQv for tapered implants (TI) was 71.67+/-5.16 and for cylindrical implants (CI) 57.15+/-4.83 (p=0.01). Mean insertion torque was 46.67+/-6.85 Ncm for TI and 35.77+/-6.72 Ncm for CI (p=0.01). In the maxilla, mean ISQ was 67.2+/-4.42 for tapered implants and 49.17+/-15.30 for cylindrical implants (p=0.01). Mean insertion torque for TI was 41.5+/-6.26 Ncm and for CI 39.17+/-6.34 Ncm (p>0.05). For tapered implants, no correlation could be found between implant diameter and primary stability. But for cylindrical implants there was a statistically significant correlation between implant diameter and primary stability: ITv (p=0.03); ISQv (p=0.04). CONCLUSIONS: Within the limits of the present study, tapered shaped implants achieve higher primary stability measured through ISQ and insertion torque values. Moreover, for cylindrical implants positive correlation has been established between implant diameter and primary stability. PMID- 26827073 TI - On the Use of Molecular Dynamics Simulations for Probing Allostery through DNA. AB - A recent study described an allosteric effect in which the binding of a protein to DNA is influenced by another protein bound nearby. The effect shows a periodicity of ~10 basepairs and decays with increasing protein-protein distance. As a mechanistic explanation, the authors reported a similar periodic, decaying pattern of the correlation coefficient between major groove widths inferred from a shorter molecular dynamics simulation. Here we show that in a state-of-the-art, microsecond-long simulation of the same DNA sequence, the periodicity of the correlation coefficient is not observed. To study the problem further, we extend an earlier mechanical model of DNA allostery based on constrained minimization of effective quadratic deformation energy of the DNA. We demonstrate that, if the constraints mimicking the bound proteins are properly applied, the periodicity in the binding energy is indeed recovered. PMID- 26827078 TI - Break point. PMID- 26827069 TI - Osteonecrosis of the jaw induced by receptor activator of nuclear factor-kappa B ligand (Denosumab) - Review. AB - BACKGROUND: Denosumab, an anti-resorptive agent, IgG2 monoclonal antibody for human Receptor activator of nuclear factor-kappa B ligand (RANKL), has been related to the occurrence of osteonecrosis of the jaws. Thus, the aim of this study was to review the literature from clinical case reports, regarding the type of patient and the therapeutic approach used for osteonecrosis of the jaws induced by chronic use of Denosumab. MATERIAL AND METHODS: For this, a literature review was performed on PubMed, Medline and Cochrane databases, using the keywords "Denosumab" "anti-RANK ligand" and "Osteonecrosis of jaw". To be included, articles should be a report or a serie of clinical cases, describing patients aged 18 years or over who used denosumab therapy and have received any therapy for ONJ. RESULTS: Thirteen complete articles were selected for this review, totaling 17 clinical cases. The majority of ONJ cases, patients receiving Denosumab as treatment for osteoporosis and prostate cancer therapy. In most cases, patients affected by ONJ were women aged 60 or over and posterior mandible area was the main site of involvement. Diabetes pre-treatment with bisphosphonates and exodontia were the most often risk factors related to the occurrence of this condition. Systemic and local antibiotic therapy with or without surgical debridement was the most used treatment for ONJ resolution. CONCLUSIONS: It is concluded that the highest number of ONJ cases caused by the use of anti-RANKL agents occurred in female patients, aged 60 years or older, under treatment for osteoporosis and cancer metastasis, and the most affected region was the mandible posterior. PMID- 26827081 TI - Etiology and Treatment of Pedal Wounds in the Diabetic Patient. PMID- 26827083 TI - Surgical Management of Chronic Wounds. AB - In this article, we outline the important role the surgeon plays in the management of chronic wounds. Debridement and washout are required for grossly infected wounds and necrotizing soft tissue infections. Cutaneous cancers such as squamous cell carcinomas may contribute to chronic wounds and vice versa; if diagnosed, these should be treated with wide local excision. Arterial, venous, and even lymphatic flows can be restored in select cases to enhance delivery of nutrients and removal of metabolic waste and promote wound healing. In cases where vital structures, such as bones, joints, tendons, and nerves, are exposed, vascularized tissue transfers are often required. These tissue transfers can be local or remote, the latter of which necessitates anastomoses of arteries and veins. Pressure sores are managed by relieving pressure, treating acute trauma or infection, and using rotation fasciocutaneous flaps. Lastly, the surgeon must always consider the possibility of osteomyelitis and retained foreign body as etiology for chronic wounds. PMID- 26827082 TI - The Mechanism of Hyperbaric Oxygen Therapy in the Treatment of Chronic Wounds and Diabetic Foot Ulcers. AB - Non-healing wounds are a growing public health concern, and more than $25 billion per year in the US are spent caring for patients with chronic wounds. Many of these patients are referred to specialized wound centers, where hyperbaric oxygen therapy (HBO2T) has become a mainstay in healing wounds, especially diabetic foot ulcers (DFU). However, it is costly, with a typical course of therapy running into the tens of thousands of dollars. Presently, as many as 30-40% of DFU patients with Wagner's Grade 3 and 4 ulcers treated with HBO2T fail to heal by 24 weeks. Unfortunately, the patient will have already received lengthy therapy (30 60 daily treatments over 6-10 week time period) before having the wound deemed non-responsive. Currently, practitioners employ a combination of clinical markers, diagnostic testing and a four-week preliminary healing response, but this approach is inaccurate and delays definitive identification of HBO2T responder and non-responder phenotypes. PMID- 26827071 TI - Long-term outcome of dental implants after maxillary augmentation with and without bone grafting. AB - BACKGROUND: This study aims to evaluate the technique of sinus bone reformation, which consists of elevating the sinus membrane and placement the implant without bone graft, compared with the widely-used technique involving raising the maxillary sinus and grafting, using animal hydroxyapatite as the filler, while simultaneously fixing the implants. MATERIAL AND METHODS: This is a retrospective study on two groups of patients who underwent elevation of the sinus membrane and simultaneous placement of the implant. The grafting technique was applied to one group, while the other had no graft. An alveolar ridge height of 4 to 7 mm was necessary. Radiological control was undertaken at 6 months and one year post prosthetic loading. In each group 38 implants were placed. RESULTS: No significant behavioural differences were observed in the implants according to the Albrektsson success criteria. Implant failure was observed in 2 implants from the bone grafting group (success rate 93%) and in 1 implant from the reformation group (success rate 97%). In this group, bone formation was observed on both sides of each implant, the bone gain was measured using image management software (2.7+/-0.9mm mesial and 2.6+/-0.9mm distal). There was no correlation between mesial and distal bone gain and implant's length. CONCLUSIONS: The results indicate that bone reformation is a valid technique in cases involving atrophy of the posterior maxilla. Primary stability, maintenance of space by the implant, and the formation of a blood clot are crucial in this technique in order to achieve bone formation around the implant. It is an alternative to the conventional technique of sinus lift with filling material, and has several advantages over this procedure, including a lower infection risk, as it does not involve a biomaterial, reduced cost, a simpler technique, and better acceptance by the patient. PMID- 26827080 TI - State of Wound Care in Rhode Island. PMID- 26827068 TI - Retrospective study of 289 odontogenic tumors in a Brazilian population. AB - BACKGROUND: Odontogenic tumors (OTs) are considered important among oral lesions because of their clinicopathological heterogeneity, and variable biological behavior. This paper aims to determine the frequency and distribution of OTs, over a period of 10 years, at a public university in Northeastern Brazil and compare this data with previous reports. MATERIAL AND METHODS: We reviewed all cases of OTs from oral pathology laboratory of University of Pernambuco (UPE), from 2004 to 2014. Diagnoses were re-evaluated and the tumors were classified according to the latest (2005) World Health Organization Classification of Tumors. In addition, we searched in the English-language literature retrospective studies on OTs that used the same classification. RESULTS: Within the total of 6028 oral biopsies, 289 (4.79%) were OTs. Of these, 287 (99.3%) were benign and 2 (0.7%) were malignant. The overall incidence was 31.1/million. Mandible-maxilla ratio was 2.5:1 and mean age 35 years. Keratocystic odontogenic tumor (KCOT) (34.6%) was the most frequent lesion, followed by ameloblastoma (AMB) (32.9%) and odontoma (ODO) (11.4%). CONCLUSIONS: OTs are uncommon neoplasms with geographic variation. Our clinicopathological features are according to literature. In the present study, KCOT was the most frequent one, showing that the new classification of OTs altered the distribution of these lesions and possibly made KCOT the most common OT observed in diagnostic services worldwide. PMID- 26827084 TI - Wound Healing in Older Adults. AB - Impaired wound healing in the elderly represents a major clinical problem that is growing as our population ages. Wound healing is affected by age and by co-morbid conditions, particularly diabetes and obesity. This is particularly important in Rhode Island as the state has a very high percentage of vulnerable older adults. A multi- disciplinary approach that incorporates the skills of a comprehensive wound center with specialized nursing, geriatric medicine and palliative care will facilitate rapid wound healing, reduce costs and improve outcomes for our older adults that suffer from 'problem wounds'. PMID- 26827077 TI - Association of vitamin D and dental caries in children: Findings from the National Health and Nutrition Examination Survey, 2005-2006. AB - BACKGROUND: The authors sought to determine associations between serum vitamin D levels and dental caries in noninstitutionalized children aged 5 to 12 years in the United States. METHODS: The authors used National Health and Nutrition Examination Survey, 2005-2006, data to study childhood caries and vitamin D. Vitamin D deficiency and inadequacy were defined as serum 25-hydroxyvitamin D (25[OH]D) less than 30 nanomoles per liter and between 30 and 49 nmol/L, respectively. Associations between vitamin D and caries experience (a combined measure of untreated caries or restorations) were examined after adjustment for confounders using multivariate logistic regression at a critical value of 5%. Sample weights were used to generate nationally representative estimates. RESULTS: The overall prevalence of serum 25(OH)D less than 30 nmol/L and 25(OH)D between 30 and 49 nmol/L among 5- to 12-year-olds was 3% and 16%, respectively. Prevalence of 25(OH)D less than 30 nmol/L and 25(OH)D between 30 and 49 nmol/L among children with caries experience was 2% and 16%, respectively. Multivariate logistic regression analysis found no significant association between vitamin D and caries experience (P = .78). Furthermore, this association was not significant after adjusting for age, sex, race and ethnicity, ratio of family income to poverty threshold, and sugar consumption (P = .46). CONCLUSIONS: The authors did not find a significant association between 25(OH)D status and caries experience in US children who participated in NHANES, 2005-2006. PRACTICAL IMPLICATIONS: The authors' findings do not support existing evidence of an association between caries and vitamin D. PMID- 26827086 TI - A Demographic Exploration of Whole Body Donors at the Alpert Medical School of Brown University. AB - OBJECTIVE: To examine and characterize the occupational histories of individuals who donated their whole bodies to the Anatomical Gift Program at Warren Alpert Medical School (AMS) from the academic years 2003-2004 to 2013-2014. DESIGN AND METHODS: A retrospective chart review of 491 individuals who donated their whole bodies to Alpert Medical School was conducted upon IRB approval from Brown University. Demographic, social, and occupational histories were abstracted for analysis and review. There were no interventions. Descriptive statistics, Student T-test and Difference in Proportions Test were used to characterize information abstracted from donor applications to the Anatomical Gift Program. PRIMARY RESULTS: From academic years 2003-2004 to 2013-2014, 491 individuals donated their bodies to the Anatomical Gift Program. Donors were split equally by gender (female = 52%; male = 48%). The median age of donors was 82 years; the vast majority self-identified as white (98%). The majority of donors came from occupations involved with industry (23%) or office work, hospitality and retail (24%). Of the 491 body donors, 2 were physicians (0.4%). PRINCIPAL CONCLUSIONS: Our data demonstrate that in the past decade, physicians have made few contributions to AMS. This remains in concert with current literature showing a lack of physician whole body donors. Future research must explore physician attitudes towards whole body donation. PMID- 26827070 TI - Correlation between periodontal disease management and metabolic control of type 2 diabetes mellitus. A systematic literature review. AB - BACKGROUND: Diabetes and periodontal disease share common features in terms of inflammatory responses. Current scientific evidence suggests that treatment of periodontal disease might contribute to glycemic control. The objective of the study is a review of the last three years. MATERIAL AND METHODS: A literature search was performed in the MEDLINE (PubMed), Cochrane, and Scopus databases, for articles published between 01-01-2013 and 30-06-2015, applying the key terms "periodontal disease" AND "diabetes mellitus". The review analyzed clinical trials of humans published in English and Spanish. RESULTS: Thirteen clinical trials were reviewed, representing a total of 1,912 patients. Three of them had samples of <40 patients, making a total of 108 patients and the remaining ten samples had >40 patients, representing a total of 1,804. Only one article achieved a Jadad score of five. Seven articles (998 patients, 52.3% total), presented a statistically significant decrease in HbA1c (p<0.05) as a result of periodontal treatment. In the six remaining articles (representing 914 patients, 47.8% of the total), the decrease in HbA1c was not significant. Patient follow-up varied between 3 to 12 months. In three articles, the follow-up was of 3, 4, and 9 months, in two 6 and 12 months. CONCLUSIONS: The majority of clinical trials showed that radicular curettage and smoothing, whether associated with antibiotics or not, can improve periodontal conditions in patients with diabetes mellitus. However, few studies suggest that this periodontal treatment improves metabolic control. However, there is no clear evidence of a relation between periodontal treatment and improved glycemic control in patients with type 2 diabetes mellitus. PMID- 26827088 TI - An Atypical Presentation of a Thalamic Stroke in a Young Adult with Ankylosing Spondylitis and an Atrial Septal Defect. PMID- 26827087 TI - A Case of Stroke due to Pulmonary Venous Thrombosis. AB - Pulmonary vein thrombosis (PVT) is a rare but potentially lethal disease. It most commonly occurs as a complication of malignancy, post-lung surgery or atrial fibrillation. Thrombi are typically detected using a variety of imaging modalities including transesophageal echo, CT-scan, magnetic resonance imaging (MRI) or pulmonary angiography. Treatment consists of anticoagulation. Here we report a case of a middle-aged male with systolic left ventricular dysfunction who presented with a stroke due to embolization from a pulmonary vein thrombus diagnosed on CT scan. Etiology of the thrombosis was felt to be secondary to severe systolic dysfunction. Based upon this case report, we believe that pulmonary venous embolism should be considered as a cause of cryptogenic stroke in patients with a significantly reduced cardiac systolic function. PMID- 26827094 TI - Authors' Response to Letter Regarding "Questionable validity of the catheter associated urinary tract infection metric used for value-based purchasing". PMID- 26827092 TI - False-positive QuantiFERON TB-Gold test due to Mycobacterium gordonae. AB - We report a case of QuantiFERON TB-Gold conversion associated to Mycobacterium gordonae in an elderly male from an assisted living facility without known risk factors for tuberculosis. This knowledge of environmental mycobacteria causing positive quantiferon assays is important to avoid unnecessary treatment of false positive latent tuberculosis, especially in the absence of well-established positive predictive value of quantiferon conversion. PMID- 26827090 TI - Understanding Ubiquinone. AB - Ubiquinone (UQ; also known as coenzyme Q; CoQ) is a mobile component of the mitochondrial electron transport chain, where it acts as a pro-oxidant in its ubisemiquinone state. Despite this, UQ is also believed to be a membrane antioxidant. These properties place UQ at the center of hotly debated questions about how mitochondria and reactive oxygen species (ROS) impact aging and disease. New studies using transgenic mouse models have provided unexpected insights into whether, and how, UQ is required in various processes, cell types, and subcellular locations. These studies have not only shed light on the role of mitochondria and ROS in the aging process, but also question the mechanisms of action by which UQ might function as a therapeutic agent. PMID- 26827091 TI - Evaluation of a fluorescent immunoassay rapid test (SofiaTM) for detection of influenza A+B and RSV in a tertiary pediatric setting. AB - In response to the lack of sensitivity and reproducibility of previously marketed rapid antigen detection tests, a novel fluorescent immunoassay was recently developed. This new assay offers rapidity and automated reading. More characterization of this assay is needed. The aim of this study was to assess diagnostic performance of Sofia influenza A+B and respiratory syncytial virus (RSV) while compared to traditional viral cell culture. A total of 416 respiratory samples were analyzed prospectively with both methods in a tertiary pediatric center. Sensitivity and specificity of the SofiaTM test were 90.0% and 98.0% for influenza A, 90.9% and 98.9% for influenza B, and 87.7% and 94.7% for RSV compared to traditional cell culture. Overall, Sofia influenza A+B and RSV assays performed well in comparison to culture in a pediatric population. PMID- 26827095 TI - Impact of Androgen Deprivation Therapy on High-level Physical Performance. PMID- 26827102 TI - [A rare cause of haemorrhagic pleurisy: Dissection of the aorta]. AB - INTRODUCTION: Haemorragic pleurisy is fairly common. The etiology is dominated by tumors and tuberculosis. The rupture of intra-thoracic vessels into the pleural cavity is a much rarer cause and the diagnosis is often delayed. OBSERVATION: A 77-year-old patient without previously known hypertension was hospitalized for investigation of a fluid density opacity occupying the entire left hemithorax. Thoracentesis revealed a non-coagulable haemorrhagic fluid. A computed tomography scan showed a Stanford type B aortic dissection. The patient was given anti hypertensive treatment for one year. CONCLUSIONS: Aortic dissection remains among the diagnoses to consider in the case of a haemorrhagic pleural effusion despite absence of the usual suggestive symptoms. PMID- 26827093 TI - Wide-spectrum activity of a silver-impregnated fabric. AB - Fabrics, such as clothing, drapes, pillowcases, and bedsheets are potential sources of pathogenic bacteria and viruses. We found fabrics (ie, professional clothing, pillowcases, and lab coats) treated with a silver-impregnated material to be effective in significantly reducing a wide spectrum of ordinary and drug resistant microorganisms, including Salmonella, methicillin-resistant Staphylococcus aureus, Propionibacterium acnes, Trichphyton mentagrophytes, and norovirus. Fabrics impregnated with antimicrobial agents help provide an additional barrier to the transport or reservoir of pathogens in health care environments. PMID- 26827096 TI - Regional differences in plastic ingestion among Southern Ocean fur seals and albatrosses. AB - We provide data on regional differences in plastic ingestion for two Southern Ocean top predators: Arctocephalus fur seals and albatrosses (Diomedeidae). Fur seals breeding on Macquarie Island in the 1990s excreted small (mainly 2-5 mm) plastic fragments, probably derived secondarily from myctophid fish. No plastic was found in the scats of these seals breeding on three islands in the southwest Indian and central South Atlantic Oceans, despite myctophids dominating their diets at these locations. Compared to recent reports of plastic ingestion by albatrosses off the east coast of South America, we confirm that plastic is seldom found in the stomachs of Thalassarche albatrosses off South Africa, but found no Diomedea albatrosses to contain plastic, compared to 26% off South America. The reasons for such regional differences are unclear, but emphasize the importance of reporting negative as well as positive records of plastic ingestion by marine biota. PMID- 26827098 TI - Inhibition of the mirror generalization process in reading in school-aged children. AB - A striking error in reading is the early and sometimes persistent confusion of mirror letters such as b and d. These mirror errors are likely a result of the mirror generalization process that allows one to identify a visual stimulus regardless of its presentation side. A previous study demonstrated that preventing mirror errors in reading requires the inhibition of the mirror generalization process in expert adult readers (Borst et al., 2015). Using the same experimental paradigm, the current study aimed at replicating this result in school-aged children. Three age groups-1st, 3rd, and 5th graders-performed a negative priming study in which they were asked to determine on the primes whether two letters were identical and on the probes whether two animals facing opposite directions were identical. All three groups of children required more time to discriminate two letters that were lateral mirror images of one another (e.g., b/d) than two letters that were not (e.g., f/t). Crucially, children required more time to determine that two animals facing opposite directions were identical when preceded by two letters that were lateral mirror images of one another (b/d) than when preceded by letters that were not mirror images of one another (f/t). Importantly, the amplitude of the negative priming effect did not vary with age. Our results suggest that overcoming mirror errors in reading, regardless of the reading proficiency of school-aged children, is rooted in the ability to inhibit the mirror generalization process. PMID- 26827100 TI - Therapeutic behavior of primary care physicians in patients with atrial fibrillation taking vitamin K antagonists not adequately controlled. PMID- 26827101 TI - Adverse drug reactions and organ damage: The liver. AB - Drug-induced liver injury (DILI) is among the most challenging acute or chronic liver conditions to be handled by physicians. Despite its low incidence in the general population, DILI is a frequent cause of acute liver failure. As such, the possibility of DILI should be considered in all patients who present with acute liver damage, independent of any known pre-existing liver disease. DILI can be classified as intrinsic/dose-dependent (e.g., acetaminophen toxicity) or idiosyncratic/dose-independent, with the latter form being relatively uncommon. Amoxicillin-clavulanate is the antimicrobial that is most frequently associated with idiosyncratic DILI. Large, ongoing, prospective studies in western countries have reported other drugs associated with DILI, including nonsteroidal anti inflammatory drugs, statins, and herbal and dietary supplements. An important safety issue, DILI is one of the most frequently cited reasons for cessation of drug development during or after preclinical studies and for withdrawal of a drug from the market. This review summarizes the epidemiology, risk factors, commonly implicated drugs, clinical features, and diagnosis of DILI, with the aim of aiding physicians in the management of this debated problem. Old and new biomarkers for DILI and pharmacogenetic studies are also described. PMID- 26827097 TI - Theory of mind in middle childhood and early adolescence: Different from before? AB - Studies with preschool children have shown that language and executive function are important for theory of mind, but few studies have examined these associations in older children and in an integrative theory-guided manner. The theory of constructive operators was used as a framework to test a model of relations among mental attentional capacity, attentional inhibition, language, executive processes (shifting and updating), and higher order theory of mind in two groups of school-aged children: one in middle childhood (n=226; mean age=8.08years) and the other in early adolescence (n=216; mean age=12.09years). Results revealed a complex model of interrelations between cognitive resources and language in middle childhood that directly and indirectly predicted theory of mind. The model in early adolescence was less complex, however, and highlighted the importance of semantic language and shifting for theory of mind. Our findings suggest not only that contributors to theory of mind change over time but also that they may depend on the maturity level of the theory of mind system being examined. PMID- 26827099 TI - Cognitive ability in Swedish conscripts and future risk of venous thromboembolism: A co-relative prospective national study. AB - OBJECTIVE: Cognitive ability measured via an IQ-test (intelligence quotient) has been associated with cardiovascular (CVD) incidence. Whether cognitive ability is associated with risk of venous thromboembolism (VTE) is unknown. The present nationwide co-relative study aims to determine whether cognitive ability in male conscripts is a predictor of VTE. METHODS: A Swedish cohort of male conscripts (n=940,964) born in 1954-1970 with no history of previous VTE were followed from enlistment (1972-1990) until 2010. Data on cognitive ability, using an IQ-test at conscription, were linked with national hospital register data to calculate future risk of VTE requiring in-patient care. Using the Swedish Multi-Generation Register, we identified all full-siblings, half-siblings and first-cousin pair discordant for IQ. This co-relative design allows for adjustment for unmeasured shared genetic or environmental factors. RESULTS: A total of 5110 (0.54%) males were affected by VTE. IQ was associated with risk for VTE (hazard ratio=HR 0.87 95% confidence interval 0.84-0.89 per standard deviation [SD] increment). The association was highly time dependent with attenuation of effect over time and significant interaction between time and IQ. IQ was also associated with VTE in first-cousin pairs (HR=0.74, 0.69-0.79) but not when examining discordant half sibling pairs (HR=0.94, 0.82-1.08), and only weakly in full-sibling pairs (HR=0.91, 0.84-0.98). CONCLUSIONS: The present study suggests that familial shared environmental factors linked to cognitive ability might be involved in the etiology of VTE. However, it is unlikely that IQ by itself causes VTE. PMID- 26827074 TI - Oral fingolimod in primary progressive multiple sclerosis (INFORMS): a phase 3, randomised, double-blind, placebo-controlled trial. AB - BACKGROUND: No treatments have been approved for primary progressive multiple sclerosis. Fingolimod, an oral sphingosine 1-phosphate receptor modulator, is effective in relapse-onset multiple sclerosis, but has not been assessed in primary progressive multiple sclerosis. We assessed the safety and efficacy of fingolimod in patients with primary progressive multiple sclerosis. METHODS: In INFORMS, a multicentre, double-blind, placebo-controlled parallel-group study, patients with primary progressive multiple sclerosis recruited across 148 centres in 18 countries were randomly allocated (1:1) with computer-generated blocks to receive oral fingolimod or placebo for at least 36 months and a maximum of 5 years. Patients were initially assigned to fingolimod 1.25 mg per day or placebo (cohort 1); however, after a protocol amendment on Nov 19, 2009, patients were switched in a masked manner to fingolimod 0.5 mg, whereas those on placebo continued on matching placebo. From then onwards, patients were assigned to receive fingolimod 0.5 mg/day or placebo (cohort 2). Key inclusion criteria were age 25-65 years, clinical diagnosis of primary progressive multiple sclerosis, 1 year or more of disease progression, and two of the following criteria: positive brain MRI; positive spinal cord MRI; or positive cerebrospinal fluid. Additional eligibility criteria included disease duration of 2-10 years and objective evidence of disability progression in the previous 2 years. Patients and study investigators were masked to group assignment. We used a novel primary composite endpoint based on change from baseline in Expanded Disability Status Scale (EDSS), 25' Timed-Walk Test, or Nine-Hole Peg Test to assess time to 3-month confirmed disability progression in study participants treated for at least 3 years. All randomised patients took at least one dose of study drug. The primary efficacy analysis included all patients in cohort 2 and those assigned to placebo in cohort 1. The safety analysis included all patients in cohorts 1 and 2. This study is registered with ClinicalTrials.gov, number NCT00731692. The study is now closed. FINDINGS: 970 patients were randomly assigned between Sept 3, 2008, and Aug 30, 2011 (147 to fingolimod 1.25 mg and 133 to placebo in cohort 1; 336 to fingolimod 0.5 mg and 354 to placebo in cohort 2). The efficacy analysis set (n=823) consisted of 336 patients randomly allocated to fingolimod 0.5 mg and 487 to placebo. Baseline characteristics were similar across groups and representative of a primary progressive multiple sclerosis population (48% women, mean age 48.5 years [SD 8.4], mean EDSS 4.67 [SD 1.03], 87% free of gadolinium enhancing lesions). By end of study, 3-month confirmed disability progression had occurred in 232 and 338 patients in the fingolimod and placebo groups, respectively, resulting in Kaplan-Meier estimates of 77.2% (95% CI 71.87-82.51) of patients in the fingolimod group versus 80.3% (73.31-87.25) of patients in the placebo group (risk reduction 5.05%; hazard ratio 0.95, 95% CI 0.80-1.12; p=0.544). Safety results were generally consistent with those of studies of fingolimod in patients with relapse-onset multiple sclerosis. Lymphopenia occurred in 19 (6%) patients in the fingolimod group versus none in the placebo group, bradycardia in five (1%) versus one (<1%), and first-degree atrioventricular block in three (1%) versus six (1%). Serious adverse events occurred in 84 (25%) patients in the fingolimod group and 117 (24%) in the placebo group, including macular oedema in six (2%) versus six (1%), and basal cell carcinoma in 14 (4%) versus nine (2%). INTERPRETATION: The anti-inflammatory effects of fingolimod did not slow disease progression in primary progressive multiple sclerosis. Therapeutic strategies for primary progressive multiple sclerosis might need different approaches to those used for relapse-onset multiple sclerosis. FUNDING: Novartis Pharma AG. PMID- 26827104 TI - [Chronic obstructive pulmonary disease (COPD) and the interior environment]. AB - INTRODUCTION: In COPD, the risk attributable to smoking is very variable according to published studies. A significant number shows that the risk of COPD in non-smokers is far from negligible. The links between COPD and pollution of the interior environment vary between developed and developing countries. STATE OF THE ART: In developing countries, numerous studies have shown a link between COPD and exposure to substances derived from the combustion of biomass fuels, particularly in women where the exposure is the greatest. Nevertheless, a cause and effect relationship has not always been demonstrated. In developed countries, there is no evidence of a role of exposure to domestic interior pollution in the genesis of COPD and interior pollutants such as NO2 and particulates seem only to aggravate already existing COPD. CONCLUSION: Further studies are necessary to evaluate their role in COPD and explore the underlying mechanisms. Irritative phenomena could be involved. PMID- 26827106 TI - [Between law and recommendations: What position for the struggle against tuberculosis?]. PMID- 26827108 TI - Demographics of the Australian orthotic and prosthetic workforce 2007-12. AB - Objective Health workforce data are vital to inform initiatives to meet the future healthcare needs of our society, but there are currently no data describing the Australian orthotic and prosthetic workforce. The aim of the present study was to describe demographic changes in the Australian orthotic and prosthetic workforce from 2007 to 2012. Methods In the present retrospective time series study, data from the Australian Orthotic Prosthetic Association member database were analysed for trends from 2007 to 2012. Data describing the absolute number of practitioners, the number of practitioners per 100000 population, age, gender, state or territory of residence and service location (i.e. metropolitan, regional and remote) were analysed for significant changes over time using linear regression models. Results Although the number of orthotist/prosthetists in Australia increased (P=0.013), the number of orthotist/prosthetists per 100000 population remained unchanged (P=0.054). The workforce became younger (P=0.004) and more female (P=0.005). Only Victoria saw an increase in the proportion of orthotist/prosthetists in regional and remote areas. There was considerable state to-state variation. Only Victoria (P=0.01) and Tasmania (P=0.003) saw an increase in the number of orthotist/prosthetists per 100000 population. Conclusions The orthotic and prosthetic workforce has increased proportionately to Australia's population growth, become younger and more female. The proportion of practitioners in regional and remote areas has remained unchanged. These data can help inform workforce initiatives to increase the number of orthotist/prosthetists relative to the Australian population and make the services of orthotist/prosthetists more accessible to Australians in regional and remote areas. What is known about the topic? Currently, there are no demographic data describing changes in the Australian orthotic and prosthetic workforce over time. These data are vital to inform initiatives to increase the size of the workforce, locate practitioners where health services are most needed and thereby plan to meet the future health care needs of our society. What does this paper add? This paper describes changes in the Australian orthotic and prosthetic workforce, where previously these data have not been available as part of federal initiatives to plan for future workforce needs. What are the implications for practitioners? Demographic data describing changes in the orthotic and prosthetic workforce are needed to inform workforce initiatives that improve access in regional and remote Australia, and retain a younger and more female workforce. PMID- 26827107 TI - Chemotherapy effectiveness and mortality prediction in surgically treated osteosarcoma dogs: A validation study. AB - Canine osteosarcoma is the most common bone cancer, and an important cause of mortality and morbidity, in large purebred dogs. Previously we constructed two multivariable models to predict a dog's 5-month or 1-year mortality risk after surgical treatment for osteosarcoma. According to the 5-month model, dogs with a relatively low risk of 5-month mortality benefited most from additional chemotherapy treatment. In the present study, we externally validated these results using an independent cohort study of 794 dogs. External performance of our prediction models showed some disagreement between observed and predicted risk, mean difference: -0.11 (95% confidence interval [95% CI]-0.29; 0.08) for 5 month risk and 0.25 (95%CI 0.10; 0.40) for 1-year mortality risk. After updating the intercept, agreement improved: -0.0004 (95%CI-0.16; 0.16) and -0.002 (95%CI 0.15; 0.15). The chemotherapy by predicted mortality risk interaction (P value=0.01) showed that the chemotherapy compared to no chemotherapy effectiveness was modified by 5-month mortality risk: dogs with a relatively lower risk of mortality benefited most from additional chemotherapy. Chemotherapy effectiveness on 1-year mortality was not significantly modified by predicted risk (P-value=0.28). In conclusion, this external validation study confirmed that our multivariable risk prediction models can predict a patient's mortality risk and that dogs with a relatively lower risk of 5-month mortality seem to benefit most from chemotherapy. PMID- 26827105 TI - [Primitive sternoclavicular septic arthritis]. AB - INTRODUCTION: Sternoclavicular infections are unusual, and it even more unusual for infection to occur here as a primary site. CASE REPORT: We report the case of a 53-year-old patient with no prior medical history or risk factor who consulted because of sternal swelling of inflammatory character. CT-scan, bacteriological and histological analysis of samples concluded the diagnosis of primary sternoclavicular staphylococcal septic arthritis. Management consisted of antibiotics and was associated with a flattening of the lesion. The outcome at 6 months was favorable. CONCLUSION: Sternoclavicular infections should be evoked early in the course of sternoclavicular pain in order to avoid any locoregional complications and mostly mediastinitis. PMID- 26827109 TI - Deep Brain Stimulation for Tourette-Syndrome: A Systematic Review and Meta Analysis. AB - BACKGROUND: A significant proportion of patients with Tourette syndrome (TS) continue to experience symptoms across adulthood that in severe cases fail to respond to standard therapies. For these cases, deep brain stimulation (DBS) is emerging as a promising treatment option. OBJECTIVE: We conducted a systematic literature review to evaluate the efficacy of DBS for GTS. METHODS: Individual data of case reports and series were pooled; the Yale Global Tic Severity Scale (YGTSS) was chosen as primary outcome parameter. RESULTS: In total, 57 studies were eligible, including 156 cases. Overall, DBS resulted in a significant improvement of 52.68% (IQR = 40.74, p < 0.001) in the YGTSS. Analysis of controlled studies significantly favored stimulation versus off stimulation with a standardized mean difference of 0.96 (95% CI: 0.36-1.56). Disentangling different target points revealed significant YGTSS reductions after stimulation of the thalamus, the posteroventrolateral part and the anteromedial part of the globus pallidus internus, the anterior limb of the internal capsule and nucleus accumbens with no significant difference between these targets. A significant negative correlation of preoperative tic scores with the outcome of thalamic stimulation was found. CONCLUSIONS: Despite small patient numbers, we conclude that DBS for GTS is a valid option for medically intractable patients. Different brain targets resulted in comparable improvement rates, indicating a modulation of a common network. Future studies might focus on a better characterization of the clinical effects of distinct regions, rather than searching for a unique target. PMID- 26827103 TI - [Chronic alveolar condensations with erythematous cutaneous lesions]. PMID- 26827114 TI - Liberating data: the crucial weapon in the fight against NCDs. PMID- 26827113 TI - Developing equity in capacity of paediatric endocrinology subspecialists worldwide. PMID- 26827089 TI - Stress-Induced EGFR Trafficking: Mechanisms, Functions, and Therapeutic Implications. AB - Epidermal growth factor receptor (EGFR) has fundamental roles in normal physiology and cancer, making it a rational target for cancer therapy. Surprisingly, however, inhibitors that target canonical, ligand-stimulated EGFR signaling have proven to be largely ineffective in treating many EGFR-dependent cancers. Recent evidence indicates that both intrinsic and therapy-induced cellular stress triggers robust, noncanonical pathways of ligand-independent EGFR trafficking and signaling, which provides cancer cells with a survival advantage and resistance to therapeutics. Here, we review the mechanistic regulation of noncanonical EGFR trafficking and signaling, and the pathological and therapeutic stresses that activate it. We also discuss the implications of this pathway in clinical treatment of EGFR-overexpressing cancers. PMID- 26827112 TI - Divergent associations of height with cardiometabolic disease and cancer: epidemiology, pathophysiology, and global implications. AB - Among chronic non-communicable diseases, cardiometabolic diseases and cancer are the most important causes of morbidity and mortality worldwide. Although high BMI and waist circumference, as estimates of total and abdominal fat mass, are now accepted as predictors of the increasing incidence of these diseases, adult height, which also predicts mortality, has been neglected. Interestingly, increasing evidence suggests that height is associated with lower cardiometabolic risk, but higher cancer risk, associations supported by mendelian randomisation studies. Understanding the complex epidemiology, biology, and pathophysiology related to height, and its association with cardiometabolic diseases and cancer, is becoming even more important because average adult height has increased substantially in many countries during recent generations. Among the mechanisms driving the increase in height and linking height with cardiometabolic diseases and cancer are insulin and insulin-like growth factor signalling pathways. These pathways are thought to be activated by overnutrition, especially increased intake of milk, dairy products, and other animal proteins during different stages of child development. Limiting overnutrition during pregnancy, early childhood, and puberty would avoid not only obesity, but also accelerated growth in children and thus might reduce risk of cancer in adulthood. PMID- 26827116 TI - Efficacy and tolerability of exenatide twice daily and exenatide once weekly in Asian versus White patients with type 2 diabetes mellitus: A pooled analysis. AB - AIMS: The efficacy and safety of exenatide twice daily (BID) and once weekly (QW) were assessed in Asian versus White patients with type 2 diabetes mellitus (T2DM). METHODS: This post-hoc pooled analysis evaluated patients receiving 10MUg exenatide BID for 12-30 weeks or 2mg exenatide QW for 24-30 weeks in exenatide clinical development program trials. Race was self-identified. RESULTS: A total of 4625 patients were included (exenatide BID: Asian, n=787; White, n=2223; exenatide QW: Asian, n=511; White, n=1104). At study end, glycated hemoglobin (HbA1c), fasting glucose (FG), body weight, post-prandial glucose (PPG), and PPG excursions were significantly reduced (all P<0.0001 vs baseline). For exenatide BID, HbA1c reduction was greater in Asians (P<0.0001 vs Whites), whereas HbA1c reduction did not differ by race for exenatide QW. FG reduction did not differ by race for either exenatide formulation. Weight reduction was significantly greater in Whites (P<0.0001 vs Asians), regardless of exenatide formulation. PPG reduction was greater in Asians (P<0.0001 vs Whites) for exenatide BID but did not differ by race for exenatide QW. For exenatide BID, reductions in PPG excursions for all meals were significantly greater in Asians (P<0.0001 vs Whites), whereas only post-breakfast and post-lunch excursions were significantly greater in Asians for exenatide QW (P=0.0009 and P=0.0189 vs Whites, respectively). Common adverse events included nausea, headache, and diarrhea. CONCLUSIONS: Exenatide BID and QW improved glycemic control, including PPG, in Asian and White patients with T2DM. With exenatide BID, Asian patients exhibited significantly greater reductions in HbA1c and PPG than White patients. Both exenatide formulations were well tolerated in both groups. PMID- 26827110 TI - Subjective perceived outcome of subthalamic deep brain stimulation in Parkinson's disease one year after surgery. AB - OBJECTIVES: Dissatisfaction with subthalamic deep brain stimulation (STN-DBS) despite motor improvements has been observed in Parkinson's disease (PD). Hence, we compared patient's subjective perceived outcome 12 months after surgery (12mFU) with clinical measures to identify risk factors of dissatisfaction. METHODS: Patients were examined at baseline and 12mFU. Quality of life (QoL), neuropsychiatric, cognitive and neurological functioning was measured. Patients were classified concerning their subjective outcome (negative = dissatisfaction; mixed; positive = satisfaction) at 12mFU using semi-structured interviews. First, the three groups were compared concerning interview statements. Second, repeated measures ANOVAs with group as between-subjects factor were applied to find significant effects of time, group, or interaction. Third, binary logistic regression determined predictors of dissatisfaction. RESULTS: Of the 28 enrolled patients, 25% perceived their outcome as negative, 32.1% as mixed, and 42.9% as positive. Concerning interview statements, dissatisfied patients mentioned significantly less often improved QoL and reduced medication, and reported worsening of mental state, and social interaction. For the whole sample, significant improvement over time was found for motor functioning, daily dopamine dosages, and QoL. Apathy significantly worsened over time, but dissatisfied patients were overall more apathetic and depressed than the other groups. Significant interaction of group and time was identified for QoL, which only improved in the mixed and satisfied group. Finally, preoperative apathy and axial symptoms predicted dissatisfaction with STN-DBS. CONCLUSIONS: Although motor symptoms and QoL improved in the whole sample, 25% of patients showed disappointment with STN-DBS. Especially apathy predicts dissatisfaction and should be considered preoperatively. PMID- 26827111 TI - Added value of next generation gene panel analysis for patients with elevated methylmalonic acid and no clinical diagnosis following functional studies of vitamin B12 metabolism. AB - Next generation sequencing (NGS) based gene panel testing is increasingly available as a molecular diagnostic approach for inborn errors of metabolism. Over the past 40 years patients have been referred to the Vitamin B12 Clinical Research Laboratory at McGill University for diagnosis of inborn errors of cobalamin metabolism by functional studies in cultured fibroblasts. DNA samples from patients in which no diagnosis was made by these studies were tested by a NGS gene panel to determine whether any molecular diagnoses could be made. 131 DNA samples from patients with elevated methylmalonic acid and no diagnosis following functional studies of cobalamin metabolism were analyzed using the 24 gene extended cobalamin metabolism NGS based panel developed by Baylor Miraca Genetics Laboratories. Gene panel testing identified two or more variants in a single gene in 16/131 patients. Eight patients had pathogenic findings, one had a finding of uncertain significance, and seven had benign findings. Of the patients with pathogenic findings, five had mutations in ACSF3, two in SUCLG1 and one in TCN2. Thus, the NGS gene panel allowed for the presumptive diagnosis of 8 additional patients for which a diagnosis was not made by the functional assays. PMID- 26827119 TI - [Conversion disorder in an internal medicine department: A series of 37 cases]. AB - OBJECTIVES: To describe the clinical characteristics of a series of patients presenting conversion disorder in a general internal medicine ward and outpatient clinic, the arguments retained by the physicians in favour of the diagnosis, the somatic and psychiatric co-morbidities, the management and the outcome of the disorder. METHODS: We report the study of 37 patients diagnosed with conversion disorder in an internal medicine department of a French university hospital over a period of 14 years. We retrospectively reviewed the charts of the patients and contacted their primary care physicians to obtain follow-up data. No structured instrument was used for the diagnosis of conversion disorder or for the assessment of psychiatric comorbidities. RESULTS: As expected, patients were mostly young females, although a great variety of age, gender, and socio-cultural background was observed. Motor symptoms predominated (62%). A relevant psychogenic factor was explicitly mentioned in only 43% of the cases. In many cases, organic disease was also present, and an organic cause for the symptom initially considered as conversion was suspected in 3 cases. Depressive and anxious disorders were present respectively in 38% and 35% of cases. A pain complaint was associated in half of the cases. Among patients for whom follow-up data is available, conversion symptoms persisted or recurred in 70% of cases and were associated with a poor quality of life. CONCLUSION: This case series confirms that the DSM-IV-TR criterion of "psychogenicity" (later abandoned in DSM 5) is highly problematic in clinical practice. It suggests a close relationship between conversion disorder and unexplained chronic pain. PMID- 26827121 TI - Adaptations to vision-for-action in primate brain evolution: Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael A. Arbib. PMID- 26827118 TI - Significant elevation of serum dipeptidyl peptidase-4 activity in young-adult type 1 diabetes. AB - AIMS: Currently, inhibition of dipeptidyl peptidase-4 (DPP-4) is widely used in the treatment of type 2 diabetes. Application of this strategy is awaited as a new therapeutic approach for type 1 diabetes, but the scientific basis is still lacking. This report describes the evaluation of serum DPP-4 activity in type 1 diabetes compared with control subjects, and assessment of relationships between DPP-4 activity and diabetic complication markers and metabolic variables in type 1 diabetes. METHODS: We examined serum DPP-4 activity in Japanese young-adult type 1 diabetes (n=76, females 69.7%, age 30.9 +/- 6.2 years, duration of diabetes 16.5 +/- 11.1 years; mean +/- SD) and healthy controls (n=22). Association of the enzymatic activity with diabetic micro- and macro- vascular complication markers and clinical parameters was also assessed. RESULTS: Subjects with type 1 diabetes displayed significantly higher serum DPP-4 activity than healthy controls (relative value, control: 1.00 +/- 0.28, T1D, 1.29 +/- 0.38; p=0.0011) independent of other clinical parameters. In type 1 diabetes, DPP-4 activity was positively correlated with duration of diabetes (r=0.248, p=0.031), while not correlated with HbA1c level. In univariate correlation analysis of diabetic complication markers and other metabolic parameters, coefficient of variation of R-R intervals (CVR-R) and gamma (gamma)-glutamyltransferase (GGT) levels were correlated with DPP-4 activity. GGT was extracted as an independent variable of DPP-4 activity in multivariate analysis (beta=0.213, p=0.035). CONCLUSIONS: Serum DPP-4 activity is significantly elevated in Japanese type 1 diabetes, suggesting pathophysiological significance of the enzyme in type 1 diabetes. PMID- 26827115 TI - Resting beta-cells - A functional reserve? AB - Pancreatic beta-cells play a pivotal role to synthesize and secrete insulin, as the solo source of the body. Physical as well as functional loss of beta-cells over a certain threshold result in diabetes. While the mechanisms underlying beta cell loss in various types of diabetes have been extensively studied, less is known about residual beta-cells, found even in autoimmune type 1 diabetes and type 2 diabetes with a substantial amount. Why have these beta-cells been spared? Some patients with neonatal diabetes have demonstrated the life-changing restoration of functional beta-cells that were inactive for decades but awakened in several weeks following specific treatment. The recent striking outcomes of bariatric surgery in many obese diabetic patients indicate that their beta-cells are likely "preserved" rather than irreversibly lost even in the multifactorial polygenic state that is type 2 diabetes. Collectively, the preservation of residual beta-cells in various diabetic conditions challenges us regarding our understanding of beta-cell death and survival, where their sustenance may stem from the existence of resting beta-cells under physiological conditions. We posit that beta-cells rest and that studies of this normal feature of beta-cells could lead to new approaches for potentially reactivating and preserving beta-cell mass in order to treat diabetes. PMID- 26827117 TI - The role of foregut exclusion in the deterioration of glucose and lipid metabolism induced by a high-fat diet. AB - AIM: The small intestine may be involved in the improvement of glucose and lipid metabolism after bariatric surgery; however, the role of the foregut in metabolic changes remains unclear. This study used normal rats fed a high-fat diet (HFD) after bariatric surgery to determine the role of the foregut in glucose and lipid metabolism. METHODS: Duodenum-jejunum bypass (DJB), gastrojejunostomy (GJ) and sham-operations were performed on Sprague-Dawley (SD) rats. Oral glucose tolerance, insulin sensitivity, beta-cell function, lipid profile, glucose stimulated glucose-dependent insulinotropic polypeptide (GIP) levels and glucagon like peptide-1 (GLP-1) levels were measured. The rats were observed for 24 weeks post-surgery. RESULTS: Food intake and body weight were similar between the groups during the study period (P>0.05). The DJB group exhibited better glucose and lipid metabolism than the other groups (P<0.05). Compared with the GJ group, the DJB group demonstrated superior oral glucose tolerance, insulin sensitivity and lipid profiles (P<0.05); beta-cell function in the two groups was similar (P>0.05). The GIP levels were decreased in the DJB group and increased in the GJ group (P<0.05), and the GLP-1 levels were increased in the DJB and GJ groups (P>0.05). CONCLUSIONS: We found that foregut exclusion can prevent disordered glucose and lipid metabolism. Additionally, decreased GIP secretion was associated with improvements in glucose tolerance and insulin sensitivity, particularly related to lipid metabolism. Increased GLP-1 benefited beta-cell function; however, it could not reverse the disordered glucose and lipid metabolism induced by a HFD. PMID- 26827122 TI - MHC variability in heritage breeds of chickens. AB - The chicken Major Histocompatibility Complex (MHC) is very strongly associated with disease resistance and thus is a very important region of the chicken genome. Historically, MHC (B locus) has been identified by the use of serology with haplotype specific alloantisera. These antisera can be difficult to produce and frequently cross-react with multiple haplotypes and hence their application is generally limited to inbred and MHC-defined lines. As a consequence, very little information about MHC variability in heritage chicken breeds is available. DNA-based methods are now available for examining MHC variability in these previously uncharacterized populations. A high density SNP panel consisting of 101 SNP that span a 230,000 bp region of the chicken MHC was used to examine MHC variability in 17 heritage populations of chickens from five universities from Canada and the United States. The breeds included 6 heritage broiler lines, 3 Barred Plymouth Rock, 2 New Hampshire and one each of Rhode Island Red, Light Sussex, White Leghorn, Dark Brown Leghorn, and 2 synthetic lines. These heritage breeds contained from one to 11 haplotypes per line. A total of 52 unique MHC haplotypes were found with only 10 of them identical to serologically defined haplotypes. Furthermore, nine MHC recombinants with their respective parental haplotypes were identified. This survey confirms the value of these non commercially utilized lines in maintaining genetic diversity. The identification of multiple MHC haplotypes and novel MHC recombinants indicates that diversity is being generated and maintained within these heritage populations. PMID- 26827123 TI - Fitness for purpose of pharmacy technician education and training: The case of Great Britain. AB - BACKGROUND: To enable pharmacists to become increasingly patient-centered, clinical professionals, they need to work with suitably trained and competent support staff; pharmacy technicians (PTs) may be the most appropriate to take on additional roles and responsibilities. However, clarity on PT roles, particularly in community pharmacy, is lacking, and pharmacists may be reluctant to delegate due to concerns over PTs' competence. OBJECTIVES: This paper aims to explore the fitness for purpose of PT education and training in Great Britain. METHODS: A mixed methods study was conducted in 2013-14. Semi-structured interviews were undertaken with face-to-face and distance education providers; and different types of community (n = 16) and hospital pharmacy (n = 15) employers. Interviews explored views on education delivery, work-based learning and assessment, and quality assurance; they were transcribed verbatim and analyzed thematically. Interviews informed a questionnaire that was piloted and distributed (with reminders) to all 1457 recently registered PTs. Survey data were analyzed using SPSS v20, employing comparative statistics (Mann-Whitney U, Chi-Square). University ethics approval was obtained. RESULTS: Staff in 17 Further Education (FE) colleges, 6 distance providers, 16 community pharmacies and 15 NHS organizations were interviewed. Participants from different sectors, education providers and employing organizations questioned whether standards met current practice requirements. Certain topics were considered as redundant or over-taught whereas others, such as professionalism (attitudes, behaviors), were perceived to be lacking. Hospital interviewees felt that PT education and training lacked clinical detail, whereas many community interviewees felt that requirements for PTs were more advanced than required. Various comments suggested that PTs' roles in community pharmacy were not clearly defined or sufficiently different from other support staff. In order to define appropriate and up-to-date education and training standards, comments suggested the role of PTs in all sectors of practice needed to be clearly defined. There were usable responses of the questionnaire returned from 632 PTs. Three-quarters (475; 75.9%) of respondents had trained in community. The majority (n = 550; 88.0%) were female, with a significantly larger proportion of females in community pharmacy (90.7%) than hospital (77.4% - X2 = 20.021, P < .001). The average age of respondents was 35.26 +/- 10.22. Respondents working in hospital were more likely to agree (n = 121; 84.0%) that their role in the workplace was clearly defined (U = 10740.500, Z = -2.563, P = .010) than their community colleagues (n = 303; 73.9%). CONCLUSIONS: Role clarity is required for PTs so that regulatory standards can be designed to meet current and future practice needs. This will support effective skill mix configurations to enable pharmacists, particularly in community, to take on extended, clinical roles. PMID- 26827120 TI - [Problematic Internet use, time spent online and personality traits]. AB - BACKGROUND: Internet addiction or problematic Internet use is a recent and increasingly recognized disorder which has been consistently associated with many psychiatric disorders, adding to the documented negative consequences of problematic Internet use. However, very few studies have examined the relationship between problematic Internet use and personality traits and none in a French sample. Moreover, those which have evaluated this relationship have mainly been conducted on small samples. OBJECTIVE: The main goal of our study was to explore the relationship between problematic Internet use, time spent online and personality traits in a French sample, taking into account the presence of depressive symptoms, and gender. METHODS: A sample of 276 participants aged from 18 to 50 (M=28; SD=8.9) completed a questionnaire assessing problematic Internet use, time spent online, the presence of ten personality traits and depressive symptoms. RESULTS: Our results revealed significant differences between genders. Among men, problematic Internet use was associated with personality clusters A and B while in women no cluster or personality traits were associated. Time spent online was predicted by schizoid personality traits among men and avoidant personality traits among women. DISCUSSION: Our results indicate that cluster A (schizoid and schizotypal) and cluster B traits (borderline and antisocial) play a more important role in problematic Internet use than cluster C traits among men. Differences between men and women regarding the relationships between personality traits, time online and problematic Internet use may be related to differences in the activities engaged in by men and women online. We observed that communication websites use was more prevalent among women while erotic, gambling and shopping websites use was more prevalent among men suggesting that the characteristics of problematic Internet use may vary according to gender. CONCLUSION: Few studies have examined the relationship between problematic Internet use, time spent online and personality traits, and none among a French sample. These results suggest the importance of assessing the impact of personality traits on Internet use, particularly on time spent online, by differentiating results in terms of gender and online activities. PMID- 26827124 TI - Don't assume the patient understands: Qualitative analysis of the challenges low health literate patients face in the pharmacy. AB - BACKGROUND: Low health literacy populations have difficulty understanding health information and making appropriate health decisions. Pharmacists need to ensure patients have a basic understanding of how to take their medications and understand the risks and benefits of their prescriptions. OBJECTIVE: To explore the major challenges low health literate adults face when trying to understand their medication therapy. METHODS: One-on-one semi-structured interviews were used to gather data on the major challenges low health literate adults face regarding their medication. Each interview began with a verbal health literacy assessment, followed by open-ended questions focused on medication information. After each interview was complete, a written health literacy assessment was given in English, which was later used to compare self-assessed health literacy to written health literacy scores. All interviews were audio-recorded, transcribed and analyzed using thematic analysis. RESULTS: The population sample had an average age of 67 years old and 90% had been education outside of North America. Low health literacy levels were found in 75% of participants based on the S TOFHLA and demonstrated a generally over estimated self-assessed health literacy levels. After thematic analysis, a flow chart that describes the low health literate population's pharmacy experience with medication information was developed to explain the cause and effect of challenges faced with current pharmacy medication information. Also, the major challenges patients with low health literacy face with current medication information from the pharmacy were limited time with pharmacists, understanding medication information, forgetting to take medication, side effects and food-drug interactions. CONCLUSION: Future interventions targeted to improving pharmacy medication information for the low health literate population should focus on addressing the challenges with limited time with pharmacists, poor understanding of medication information, forgetting to take medications, side effects and food instruction/interactions. PMID- 26827125 TI - Elevated Plasma Pancreastatin, but Not Chromogranin A, Predicts Survival in Neuroendocrine Tumors of the Duodenum. AB - BACKGROUND: Neuroendocrine tumors (NETs) of the duodenum are rare, heterogeneous, and often indolent neoplasms. We hypothesized that elevated pancreastatin levels are an indicator of a poor prognosis in well-differentiated duodenal NETs. STUDY DESIGN: Data from patients diagnosed with a primary duodenal NET were analyzed. Patients that underwent esophogogastroduodenoscopy, endoscopic ultrasound, or exploratory surgery to localize their neoplasm and whose tumors were confirmed histologically were included. RESULTS: Eighty-four patients were diagnosed with duodenal NETs from January 1991 to January 2014. Seventy-five percent and 21% of patients had their tumor localized by esophogogastroduodenoscopy and endoscopic ultrasound, respectively. The remaining 4% were localized during exploratory surgery. The 5-year Kaplan-Meier survival rate for the entire cohort (N = 84) was 80%. Survival sorted by normal vs abnormal pancreastatin level was statistically significant (p < 0.0001). Five-year survival rates were 94% and 37% for normal and abnormal pancreastatin, respectively. In contrast, survival sorted by normal vs abnormal plasma chromogranin A level was not statistically significant (p = 0.24). CONCLUSIONS: Patients with primary duodenal NETs have high 5-year survival rates. Serial monitoring of plasma pancreastatin levels can identify patients who have a poor prognosis. PMID- 26827127 TI - Manipulation of environmental oxygen modifies reactive oxygen and nitrogen species generation during myogenesis. AB - Regulated changes in reactive oxygen and nitrogen species (RONS) activities are important in maintaining the normal sequence and development of myogenesis. Both excessive formation and reduction in RONS have been shown to affect muscle differentiation in a negative way. Cultured cells are typically grown in 20% O2 but this is not an appropriate physiological concentration for a number of cell types, including skeletal muscle. The aim was to examine the generation of RONS in cultured skeletal muscle cells under a physiological oxygen concentration condition (6% O2) and determine the effect on muscle myogenesis. Primary mouse satellite cells were grown in 20% or 6% O2 environments and RONS activity was measured at different stages of myogenesis by real-time fluorescent microscopy using fluorescent probes with different specificities i.e. dihydroethidium (DHE), 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM DA) and 5-(and 6)-chloromethyl-2',7' -dichlorodihydrofluorescein diacetate (CM-DCFH-DA). Data demonstrate that satellite cell proliferation increased when cells were grown in 6% O2 compared with 20% O2. Myoblasts grown in 20% O2 showed an increase in DCF fluorescence and DHE oxidation compared with myoblasts grown at 6% O2. Myotubes grown in 20% O2 also showed an increase in DCF and DAF-FM fluorescence and DHE oxidation compared with myotubes grown in 6% O2. The catalase and MnSOD contents were also increased in myoblasts and myotubes that were maintained in 20% O2 compared with myoblasts and myotubes grown in 6% O2. These data indicate that intracellular RONS activities in myoblasts and myotubes at rest are influenced by changes in environmental oxygen concentration and that the increased ROS may influence myogenesis in a negative manner. PMID- 26827133 TI - [Update Chagas disease]. AB - The constant migration flows have favored the presence of people with Chagas disease in regions traditionally regarded as non-endemic, such as North America, Europe, Asia and Oceania. This has forced both health authorities and professionals to be updated in order to respond to such a demand for assistance. Recent years have led to significant progress in the field of diagnosis and treatment of Chagas disease, one of the most neglected tropical diseases. Recent clinical trials are providing new evidence that makes the management of these patients, a constant challenge for the professionals involved. Innovative diagnostic tools and therapeutic regimens, allow us to face the future of Chagas disease with optimism. PMID- 26827134 TI - Helminthosis and eosinophilia in Spain (1990-2015). AB - The finding of blood eosinophilia in a patient is a relatively frequent reason to refer him/her to a Clinical Department of Infectious Diseases. The doctor usually intends to rule out a parasitic disease in the autochthonous population, travelers or immigrants. It is uncommon for an eosinophilia to be produced by protozoa infection, whereas helminth parasites are more frequently associated with an increase of eosinophil counts in the infected patient. Eosinophilia can be the only abnormal finding, or it could be part of more complex clinical manifestations suffered by the patient. Furthermore, many, but not all, helminth infections are associated with eosinophilia, and the eosinophil level (low, high) differs according to parasite stages, helminth species, and worm co-infections. The purpose of the present article is to carry out a systematic review of cases and case series on helminth infections and eosinophilia reported in Spain from 1990 to 2015, making a distinction between autochthonous and imported (immigrants and travelers) cases, and studying their relationship with immunodepression situations. PMID- 26827135 TI - Gastro Enteritis in a military population deployed in West Africa in the UK Ebola response; was the observed lower disease burden due to handwashing? AB - BACKGROUND: Travellers' diarrhoea in military populations is reported ranging from 50 to 70 cases per thousand person months. The UK personnel deployed to the Ebola Outbreak in Sierra Leone during the Ebola outbreak adopted standard measures associated with disease prevention. As part of the infection control measures against transmission of Ebola, personnel also rinsed their hands frequently in 0.05% hypochlorite. This was felt to have reduced the incidence of travellers' diarrhoea in the population and an audit was carried out to test this hypothesis. METHODS: Routine data identified diarrhoea and vomiting cases. A questionnaire sought information on traveller's diarrhoea and hand hygiene in Sierra Leone and Afghanistan. RESULTS: The incidence of Gastro Intestinal Disease for the population ranged from 23.9 Per thousand personnel per month to 74.4 per thousand personnel per month (mean 55.1 cases per thousand personnel per month). This included 4 headline outbreaks which accounted for 156 of the total number of 243 cases in the period of the deployment. The mean daily number of hand washes in Sierra Leone as reported in a survey was 17.02 (SD 8.2) and for Afghanistan was 9.06 (6.88). The mean difference was 7.94 (t 0.64 p < 0.0001.) CONCLUSION: The gastro intestinal disease incidence appeared to be at the lower end of the range reported by other groups in an environment with, arguably, a greater risk of infection. Force health protection policies were similar between Sierra Leone and Afghanistan excepting the frequency with which hands were rinsed or washed. We recommend that hand washing stations are placed at every office and communal area and not just at the dining facility in order to minimise the incidence of travellers' diarrhoea on future operations. PMID- 26827130 TI - High functioning individuals with schizophrenia have preserved social perception but not mentalizing abilities. AB - Social perception and mentalizing are fundamental social cognitive abilities that are related to functioning and are impaired in schizophrenia. A novel approach to examine the relationship between social cognition and community functioning is to first functionally categorize individuals with schizophrenia and then evaluate social cognitive performance. We evaluated differences in social perception and mentalizing among controls (CON, n=45), high functioning individuals with schizophrenia (HF-SCZ, n=36), and individuals with low functioning schizophrenia (LF-SCZ, n=24). Analyses revealed that HF-SCZ had preserved social perceptual abilities compared to LF-SCZ. Both schizophrenia groups had impaired mentalizing abilities compared to CON, but did not differ from each other. These results suggest that HF-SCZ and LF-SCZ are characterized by differences in the perceptual aspects of social cognition and encourage future research to evaluate the neural basis underlying this preserved ability. PMID- 26827129 TI - Augmentation of clozapine with electroconvulsive therapy in treatment resistant schizophrenia: A systematic review and meta-analysis. AB - The primary aim of this systematic review and meta-analysis was to assess the proportion of patients with Treatment Resistant Schizophrenia (TRS) that respond to ECT augmentation of clozapine (C+ECT). We searched major electronic databases from 1980 to July 2015. We conducted a random effects meta-analysis reporting the proportion of responders to C+ECT in RCTs and open-label trials. Five clinical trials met our eligibility criteria, allowing us to pool data from 71 people with TRS who underwent C+ ECT across 4 open label trials (n=32) and 1 RCT (n=39). The overall pooled proportion of response to C+ECT was 54%, (95% CI: 21.8-83.6%) with some heterogeneity evident (I(2)=69%). With data from retrospective chart reviews, case series and case reports, 192 people treated with C+ECT were included. All studies together demonstrated an overall response to C+ECT of 66% (95% CI: 57.5-74.3%) (83 out of 126 patients responded to C+ECT). The mean number of ECT treatments used to augment clozapine was 11.3. 32% of cases (20 out of 62 patients) with follow up data (range of follow up: 3-468weeks) relapsed following cessation of ECT. Adverse events were reported in 14% of identified cases (24 out of 166 patients). There is a paucity of controlled studies in the literature, with only one single blinded randomised controlled study located, and the predominance of open label trials used in the meta-analysis is a limitation. The data suggests that ECT may be an effective and safe clozapine augmentation strategy in TRS. A higher number of ECT treatments may be required than is standard for other clinical indications. Further research is needed before ECT can be included in standard TRS treatment algorithms. PMID- 26827136 TI - Synthesis and pharmacological evaluation of trifluoromethyl containing 4-(2 pyrimidinylamino)benzamides as Hedgehog signaling pathway inhibitors. AB - In present study, a series of novel containing trifluoromethyl 4-(2 pyrimidinylamino)benzamide derivatives were designed by the fluorine scan strategy. Their Hh signaling inhibitory activities were evaluated by Gli luciferase reporter method. The comprehensive SAR was discussed and several derivatives were found to display more potent Hh signaling inhibitory activity than positive drug vismodegib. Compound 13d was the most potent compound with IC50 of 1.44nM against Hh signaling pathway and also exhibited optimal PK properties in the in vivo PK properties study, deserved as an ideal lead compound for further study in future. PMID- 26827131 TI - Dietary Quality and Adherence to Dietary Recommendations in Patients Undergoing Hemodialysis. AB - BACKGROUND: The multiple dietary restrictions recommended to hemodialysis patients may be difficult to achieve and, at the same time, may result in nutritional deficiencies rendering a poor dietary quality. We here assess the dietary quality and adherence to renal-specific guideline recommendations among hemodialysis patients from a single center in Canary Islands, Spain. METHODS: Cross-sectional study, including 91 patients undergoing maintenance hemodialysis. Clinical data and 3-day dietary records were collected. We compared patient's reported nutrients intake with guideline recommendations. We also evaluated their alignment with current American Heart Association dietary guidelines for cardiovascular prevention. RESULTS: Seventy-seven percent and 50% of patients consumed less than the recommended daily energy and protein, respectively. Although half of the patients met the recommendations for dietary fat intake, this was accounted by an excess of saturated fat in 92% of them. Only 22% consumed sufficient fiber. A very small proportion of patients (less than 50%) met the requirements for vitamins and other micronutrients. Insufficient dietary intake was observed in most patients for all vitamins except for cobalamin. Similarly, inadequate dietary intake was observed for many minerals, by both excess (phosphorus, calcium, sodium, and potassium) and defect (magnesium). Most patients met the recommendations for iron and zinc in their diets. CONCLUSIONS: A large proportion of hemodialysis patients at our center did not meet current renal-specific dietary recommendations. The quality of the diet was considered poor and proatherogenic according to American Heart Association guidelines. PMID- 26827138 TI - Anionic surfactants enhance click reaction-mediated protein conjugation with ubiquitin. AB - The Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) has become increasingly important in the conjugation chemistry of biomolecules. For example, it is an efficient and convenient method to generate defined ubiquitin-protein conjugates. Here, we investigate the effect of surfactants on the efficiency of CuAAC for chemical protein ubiquitylation. We found that anionic surfactants enhance conjugate formation by up to 10-fold resulting in high yields even at low (i.e., micromolar) concentrations of the reactants. Notably, the herein investigated conjugates are functional and thus properly folded. PMID- 26827139 TI - Incorporation of fluorophore-cholesterol conjugates into liposomal and mycobacterial membranes. AB - Fluorescently-labeled steroids that emit intense blue light in nonpolar solvent (lambdaem (CH2Cl2)~440nm, PhiF=0.70) were prepared by treating cholesteryl chloroformate with 4-amino-1,8-naphthalimides. The lipid portion of the conjugates embeds into liposomal membrane bilayers in minutes, leaving the fluorophore exposed to the external aqueous environment. This causes a 40-nm red shift in lambdaem and significant quenching. DFT optimizations predict the conjugates to be about 30A long when fully extended, but rotation about the linker group can bring the compounds into an 'L'-shape. Such a conformation would allow the cholesteryl anchor to remain parallel to the acyl chains of a membrane while the fluorescent group resides in the interfacial region, instead of extending beyond it. When incubated with Mycobacterium smegmatis mc2 155, a bacterial species known to use natural cholesterol, the labeled steroids support growth and can be found localized in the membrane fraction of the cells using HPLC. These findings demonstrate stable integration of fluorescent cholesterols into bacterial membranes in vivo, indicating that these compounds may be useful for evaluating cholesterol uptake in prokaryotic organisms. PMID- 26827126 TI - In vivo evaluation of different alterations of redox status by studying pharmacokinetics of nitroxides using magnetic resonance techniques. AB - Free radicals, particularly reactive oxygen species (ROS), are involved in various pathologies, injuries related to radiation, ischemia-reperfusion or ageing. Unfortunately, it is virtually impossible to directly detect free radicals in vivo, but the redox status of the whole organism or particular organ can be studied in vivo by using magnetic resonance techniques (EPR and MRI) and paramagnetic stable free radicals - nitroxides. Here we review results obtained in vivo following the pharmacokinetics of nitroxides on experimental animals (and a few in humans) under various conditions. The focus was on conditions where the redox status has been altered by induced diseases or harmful agents, clearly demonstrating that various EPR/MRI/nitroxide combinations can reliably detect metabolically induced changes in the redox status of organs. These findings can improve our understanding of oxidative stress and provide a basis for studying the effectiveness of interventions aimed to modulate oxidative stress. Also, we anticipate that the in vivo EPR/MRI approach in studying the redox status can play a vital role in the clinical management of various pathologies in the years to come providing the development of adequate equipment and probes. PMID- 26827141 TI - Synthesis and biological evaluation of enantiomerically pure glyceric acid derivatives as LpxC inhibitors. AB - Inhibitors of the UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC) represent a promising class of novel antibiotics, selectively combating Gram-negative bacteria. In order to elucidate the impact of the hydroxymethyl groups of diol (S,S)-4 on the inhibitory activity against LpxC, glyceric acid ethers (R)-7a, (S)-7a, (R)-7b, and (S)-7b, lacking the hydroxymethyl group in benzylic position, were synthesized. The compounds were obtained in enantiomerically pure form by a chiral pool synthesis and a lipase catalyzed enantioselective desymmetrization, respectively. The enantiomeric hydroxamic acids (R)-7b (Ki=230nM) and (S)-7b (Ki=390nM) show promising enzyme inhibition. However, their inhibitory activities do not substantially differ from each other leading to a low eudismic ratio. Generally, the synthesized glyceric acid derivatives 7 show antibacterial activities against two Escherichia coli strains exceeding the ones of their respective regioisomes 6. PMID- 26827152 TI - Consistent, quality midwifery care: How midwifery education and the role of the midwife teacher are important contributions to the Lancet Series. PMID- 26827137 TI - Pyrazole antagonists of the CB1 receptor with reduced brain penetration. AB - Type 1 cannabinoid receptor (CB1) antagonists might be useful for treating obesity, liver disease, metabolic syndrome, and dyslipidemias. Unfortunately, inhibition of CB1 in the central nervous system (CNS) produces adverse effects, including depression, anxiety and suicidal ideation in some patients, which led to withdrawal of the pyrazole inverse agonist rimonabant (SR141716A) from European markets. Efforts are underway to produce peripherally selective CB1 antagonists to circumvent CNS-associated adverse effects. In this study, novel analogs of rimonabant (1) were explored in which the 1-aminopiperidine group was switched to a 4-aminopiperidine, attached at the 4-amino position (5). The piperidine nitrogen was functionalized with carbamates, amides, and sulfonamides, providing compounds that are potent inverse agonists of hCB1 with good selectivity for hCB1 over hCB2. Select compounds were further studied using in vitro models of brain penetration, oral absorption and metabolic stability. Several compounds were identified with predicted minimal brain penetration and good metabolic stability. In vivo pharmacokinetic testing revealed that inverse agonist 8c is orally bioavailable and has vastly reduced brain penetration compared to rimonabant. PMID- 26827143 TI - Solar Radiation Stress in Natural Acidophilic Biofilms of Euglena mutabilis Revealed by Metatranscriptomics and PAM Fluorometry. AB - The daily photosynthetic performance of a natural biofilm of the extreme acidophilic Euglena mutabilis from Rio Tinto (SW, Spain) under full solar radiation was analyzed by means of pulse amplitude-modulated (PAM) fluorescence measurements and metatrascriptomic analysis. Natural E. mutabilis biofilms undergo large-scale transcriptomic reprogramming during midday due to a dynamic photoinhibition and solar radiation stress. Photoinhibition is due to UV radiation and not to light intensity, as revealed by PAM fluorometry analysis. In order to minimize the negative effects of solar radiation, our data supports the presence of a circadian rhythm in this euglenophyte that increases their opportunity to survive. Differential gene expression throughout the day (at 12:00, 20:00 and night) was monitored by massive Illumina parallel sequencing of metatranscriptomic libraries. The transcription pattern was altered in genes involved in Photosystem II stability and repair, UV damaged DNA repair, non photochemical quenching and oxidative stress, supporting the photoinhibition detected by PAM fluorometry at midday. PMID- 26827142 TI - Exploring the status of motility, lipid bodies, deformities and size reduction in periphytic diatom community from chronically metal (Cu, Zn) polluted waterbodies as a biomonitoring tool. AB - Taxonomic metrics of diatoms are regularly used for aquatic biomonitoring, including testing for heavy metal stress. In contrast, non-taxonomical parameters in diatoms are rarely assessed. In the present study, taxonomical features of diatoms, such as cell density, chlorophyll a, species richness, and the Shannon index, were reduced at severely polluted (Cu, Zn) sites compared with less polluted sites. Some non-taxonomic parameters, such as, lipid bodies (LBs) number and size, carotenoid/chlorophyll a ratios, and frustule deformities were elevated at the severely polluted sites in comparison to the less polluted sites in both the areas. Cell size diminished and motility changed from smooth to erratic with increasing Cu and Zn pollution. Some of these behavioral and physiological changes were easily assessed (e.g., motility and formation of LBs), while morphological alterations (cell wall deformities and changes in cell size) requires more time and human expertise in diatom taxonomy. These parameters were consistent across metal concentrations of sediments, in the water, and in cells. The results illustrate the usefulness of these non-taxonomic parameters in biomonitoring, especially as early warning tools for ecotoxicity assessment and testing for sublethal effects. Some of these parameters, such as cell size and cell wall deformities, can be easily incorporated into traditional protocols, although LBs and motility metrics will require more effort. PMID- 26827146 TI - Liquid crystals as optical amplifiers for bacterial detection. AB - Interactions of bacteria with target molecules (e.g. antibiotics) or other microorganisms are of growing interest. The first barrier for targeting gram negative bacteria is layer of a Lipopolysaccharides (LPS). Liquid crystal (LC) based sensors covered with LPS monolayers, as presented in this study, offer a simple model to study and make use of this type of interface for detection and screening. This work describes in detail the production and application of such sensors based on three different LPS that have been investigated regarding their potential to serve as sensing layer to detect bacteria. The LPS O127:B8 in combination with a LC based sensor was identified to be most useful as biomimetic sensing surface. This LPS/LC combination interacts with three different bacteria species, one gram-positive and two gram-negative species, allowing the detection of bacterial presence regardless from their viability. It could be shown that even very low bacterial cell numbers (minimum 500 cell ml(-1)) could be detected within minutes (maximum 15 min). The readout mechanism is the adsorption of bacterial entities on surface bond LPS molecules with the LC serving as an optical amplifier. PMID- 26827148 TI - Direct and indirect toxicity of the fungicide pyraclostrobin to Hyalella azteca and effects on leaf processing under realistic daily temperature regimes. AB - Fungicides in aquatic environments can impact non-target bacterial and fungal communities and the invertebrate detritivores responsible for the decomposition of allochthonous organic matter. Additionally, in some aquatic systems daily water temperature fluctuations may influence these processes and alter contaminant toxicity, but such temperature fluctuations are rarely examined in conjunction with contaminants. In this study, the shredding amphipod Hyalella azteca was exposed to the fungicide pyraclostrobin in three experiments. Endpoints included mortality, organism growth, and leaf processing. One experiment was conducted at a constant temperature (23 degrees C), a fluctuating temperature regime (18-25 degrees C) based on field-collected data from the S. Llano River, Texas, or an adjusted fluctuating temperature regime (20-26 degrees C) based on possible climate change predictions. Pyraclostrobin significantly reduced leaf shredding and increased H. azteca mortality at concentrations of 40 MUg/L or greater at a constant 23 degrees C and decreased leaf shredding at concentrations of 15 MUg/L or greater in the fluctuating temperatures. There was a significant interaction between temperature treatment and pyraclostrobin concentration on H. azteca mortality, body length, and dry mass under direct aqueous exposure conditions. In an indirect exposure scenario in which only leaf material was exposed to pyraclostrobin, H. azteca did not preferentially feed on or avoid treated leaf disks compared to controls. This study describes the influence of realistic temperature variation on fungicide toxicity to shredding invertebrates, which is important for understanding how future alterations in daily temperature regimes due to climate change may influence the assessment of ecological risk of contaminants in aquatic ecosystems. PMID- 26827144 TI - Highly sensitive electrochemiluminescence detection of p53 protein using functionalized Ru-silica nanoporous@gold nanocomposite. AB - A simple, rapid response time and ultrahigh sensitive electrochemiluminescence (ECL) immunosensor based on Ru(bpy)3(2+)doped silica doped AuNPs (Ru-Si@Au nanocomposite) was developed for detection of p53 protein, a well-known tumor suppressor. The immunosensor was constructed using biotinylated capture antibody, immobilized on the glassy carbon electrode (GCE) using streptavidin modified-gold nanoparticles/thiolated graphene oxide, followed by its conjugation with the Ru silica@Au nanocomposite labeled secondary antibody to form a sandwich-type immunocomplex. The use of Ru-Si@Au nanocomposites led to a remarkable increase in the ECL intensity and, thus, the sensitivity of the method. Under the optimized conditions, the linear range of the proposed p53 immunosensor was found between 0.2 and 200 pM with a calculated limit of detection of 22.8 fM. The selectivity and reproducibility of the immunosensor was also investigated and the results showed high specificity and great stability in detecting of p53. Moreover, the ECL immunosensor was successfully applied for quantification of p53 protein in the human spiked serum samples and more importantly in the human normal and cancer skin fibroblast cells showing much satisfactory result compared with the ELISA method. The proposed immunosensor reported herein offers a considerable potential in early detection of cancer and clinical diagnosis and provides a new platform for biomarker detection. PMID- 26827140 TI - Synthesis, molecular docking and biological evaluation of N,N-disubstituted 2 aminothiazolines as a new class of butyrylcholinesterase and carboxylesterase inhibitors. AB - A series of 31 N,N-disubstituted 2-amino-5-halomethyl-2-thiazolines was designed, synthesized, and evaluated for inhibitory potential against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carboxylesterase (CaE). The compounds did not inhibit AChE; the most active compounds inhibited BChE and CaE with IC50 values of 0.22-2.3MUM. Pyridine-containing compounds were more selective toward BChE; compounds with the para-OMe substituent in one of the two dibenzyl fragments were more selective toward CaE. Iodinated derivatives were more effective BChE inhibitors than brominated ones, while there was no influence of halogen type on CaE inhibition. Inhibition kinetics for the 9 most active compounds indicated non-competitive inhibition of CaE and varied mechanisms (competitive, non-competitive, or mixed-type) for inhibition of BChE. Docking simulations predicted key binding interactions of compounds with BChE and CaE and revealed that the best docked positions in BChE were at the bottom of the gorge in close proximity to the catalytic residues in the active site. In contrast, the best binding positions for CaE were clustered rather far from the active site at the top of the gorge. Thus, the docking results provided insight into differences in kinetic mechanisms and inhibitor activities of the tested compounds. A cytotoxicity test using the MTT assay showed that within solubility limits (<30MUM), none of the tested compounds significantly affected viability of human fetal mesenchymal stem cells. The results indicate that a new series of N,N disubstituted 2-aminothiazolines could serve as BChE and CaE inhibitors for potential medicinal applications. PMID- 26827150 TI - Kinematics and kinetics during walking in individuals with gluteal tendinopathy. AB - BACKGROUND: Lateral hip pain during walking is a feature of gluteal tendinopathy but little is known how walking biomechanics differ in individuals with gluteal tendinopathy. This study aimed to compare walking kinematics and kinetics between individuals with and without gluteal tendinopathy. METHODS: Three-dimensional walking-gait analysis was conducted on 40 individuals aged 35 to 70 years with unilateral gluteal tendinopathy and 40 pain-free controls. An analysis of covariance was used to compare kinematic and kinetic variables between groups. Linear regression was performed to investigate the relationship between kinematics and external hip adduction moment in the gluteal tendinopathy group. FINDINGS: Individuals with gluteal tendinopathy demonstrated a greater hip adduction moment throughout stance than controls (standardized mean difference ranging from 0.60 (first peak moment) to 0.90 (second peak moment)). Contralateral trunk lean at the time of the first peak hip adduction moment was 1.2 degrees greater (P=0.04), and pelvic drop at the second peak hip adduction moment 1.4 degrees greater (P=0.04), in individuals with gluteal tendinopathy. Two opposite trunk and pelvic strategies were also identified within the gluteal tendinopathy group. Contralateral pelvic drop was significantly correlated with the first (R=0.35) and second peak (R=0.57) hip adduction moment, and hip adduction angle with the second peak hip adduction moment (R=-0.36) in those with gluteal tendinopathy. INTERPRETATION: Individuals with gluteal tendinopathy exhibit greater hip adduction moments and alterations in trunk and pelvic kinematics during walking. Findings provide a basis to consider frontal plane pelvic control in the management of gluteal tendinopathy. PMID- 26827156 TI - Hermann von Helmholtz: Physician, physicist and inventor. PMID- 26827149 TI - Circulating microRNAs and hypertension--from new insights into blood pressure regulation to biomarkers of cardiovascular risk. AB - Hypertension is a leading cause of cardiovascular morbidity and mortality worldwide, yet the molecular mechanisms underpinning the development of high blood pressure remain incompletely understood. MicroRNAs are small, non-coding RNA molecules approximately 22 nucleotides in length that act as post transcriptional regulators of gene expression. We highlight, through a review of recent literature, that studies on circulating microRNAs have provided novel insights into blood pressure regulation. They have also complemented tissue-based and animal-based experiments in shedding new light on our understanding of established pathways in hypertension, such as the renin-angiotensin system. Despite a number of challenges, we believe microRNAs herald particular potential in becoming effective biomarkers of target-organ damage in hypertension. PMID- 26827151 TI - Brief Symptom Inventory symptom profiles of outpatients with borderline intellectual functioning and major depressive disorder or posttraumatic stress disorder: Comparison with patients from regular mental health care and patients with Mild Intellectual Disabilities. AB - INTRODUCTION: In most countries, people with borderline intellectual functioning (BIF) are not considered a separate group in mental health care. There is little to no research on the impact of BIF on the presentation, nature and severity of mental health problems. The aim of the present exploratory study was to compare, in a naturalistic setting of patients referred to secondary care, symptom profiles of patients with BIF diagnosed with either major depressive disorder (MDD) or posttraumatic stress disorder (PTSD) to patients from regular mental health care (RMHC) and patients with Mild ID diagnosed with the same disorders. METHODS: We used a cohort of adolescent and adult outpatients (aged 16-88) with or without BIF diagnosed with a primary diagnosis MDD or PTSD. Primary outcome was the nature and severity of psychopathological symptoms assessed at baseline using the Brief Symptom Inventory. All outcomes were adjusted for gender and age. RESULTS: Results showed that BIF patients with a primary diagnosis MDD reported less severe symptoms on BSI Total and the subscales Depression, Obsession Compulsion and Psychoticism than patients from regular mental health care (RMHC). There were no statistically significant differences in reported symptom severity on BSI Total and the different BSI subscales between BIF patients with PTSD and either patients from RMHC or patients with Mild ID. Patients Mild ID, did report significantly less severe symptoms on the subscale Depression and on the subscale Psychoticism than patients from RMHC. DISCUSSION: Since there were no other published studies into symptom profiles in patients with BIF compared to either patients with higher or lower levels of cognitive functioning, the study was mainly exploratory in nature, providing direction for future research. Results indicate that symptom profiles did not widely differ, but that there might be some characteristics unique to patients BIF separating them as a group from both patients from RMHC and patients with Mild ID. PMID- 26827145 TI - Electronic tongue for microcystin screening in waters. AB - The potentiometric E-tongue system was employed for water toxicity estimation in terms of cyanobacterial microcystin toxins (MCs) detection. The data obtained from E-tongue were correlated to the MCs content detected by the standard chromatographic technique UHPLC-DAD (Ultra High Performance Liquid Chromatography with Diode Array Detector), as far as by the colorimetric enzymatic approach. The prediction of MCs released by toxic Microcystis aeruginosa strains was possible with Root Mean Squared Error of Validation (RMSEV) lower or very close to 1ug/L, the provisional guideline value of WHO for MCs content in potable waters. The application of E-tongue system opens up a new perspective offset for fast and inexpensive analysis in the field of environmental monitoring, offering also the possibility to distinguish toxin producing and non-toxic M. aeruginosa strains present in potable water. PMID- 26827147 TI - A novel non-enzymatic glucose sensor based on Pt3Ru1 alloy nanoparticles with high density of surface defects. AB - A novel non-enzymatic glucose sensor based on a glassy carbon electrode modified with Pt3Ru1 alloy nanoparticles (Pt3Ru1/GCE) was fabricated. Pt3Ru1 alloy nanoparticles were prepared by a reverse microemulsion method at room temperature. The X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDS) demonstrate that Pt3Ru1 nanoparticles are disordered alloy with face central cubic (fcc) structure and the atom ratio of Pt and Ru is 3:1. The high resolution transmission electron microscopy (HRTEM) images show that Pt3Ru1 alloy nanoparticles were aggregated with a high density of surface defects. Furthermore, the sensor properties of Pt3Ru1/GCE were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and chronoamperometry (CA) in 0.01 M PBS (pH 7.4). The results indicate that the proposed sensor exhibits a wide linear range of 5 * 10(-7)M to 10(-2)M (R(2)=0.9988) with a low detection limit of 0.3 MUM for glucose. Moreover, the sensor demonstrates good sensitivity, stability, reproducibility, and better anti interference performance toward ascorbic acid (AA), uric acid (UA), and fructose (Fru). PMID- 26827158 TI - Ability to detect high-grade squamous anal intraepithelial lesions at high resolution anoscopy improves over time. AB - Background Anal cancer is increasing in incidence, has very high rates in specific populations and shares many similarities with cervical cancer. High grade squamous intraepithelial lesions (HSIL) are regarded as precursors to anal cancer. High resolution anoscopy (HRA), which is derived from colposcopy, is the only currently available tool that can identify areas of the anal canal for targeted biopsy and identification of HSIL. METHODS: This study investigated the ability over a period of time of a single anoscopist to identify and adequately biopsy HSIL, correlating with contemporary anal cytological findings. RESULTS: Four hundred paired cytology and histology samples collected from 283 patients over a 7-year period from 2004 to 2010 were compared. There was a significant increase in HSIL detection rates when anal squamous cells of undetermined significance (ASC-US; 38.6-66.0%) or low-grade squamous intra-epithelial lesion (38.8-68.3%) were taken as cut-off points (P<0.001 for both). Detection rates did not change significantly when atypical squamous cells-cannot exclude HSIL (ASC-H) or a higher grade lesion (70-76.6%) was taken as the cut-off point. CONCLUSIONS: The increase in ability to detect histological HSIL over time and with increasing experience has the potential to impact on delivery of clinical services and the interpretation of clinical trial data. Further studies are required to determine the extent of this effect on other clinicians practising HRA. PMID- 26827128 TI - Understanding the genetic liability to schizophrenia through the neuroepigenome. AB - The Psychiatric Genomics Consortium-Schizophrenia Workgroup (PGC-SCZ) recently identified 108 loci associated with increased risk for schizophrenia (SCZ). The vast majority of these variants reside within non-coding sequences of the genome and are predicted to exert their effects by affecting the mechanism of action of cis regulatory elements (CREs), such as promoters and enhancers. Although a number of large-scale collaborative efforts (e.g. ENCODE) have achieved a comprehensive mapping of CREs in human cell lines or tissue homogenates, it is becoming increasingly evident that many risk-associated variants are enriched for expression Quantitative Trait Loci (eQTLs) and CREs in specific tissues or cells. As such, data derived from previous research endeavors may not capture fully cell type and/or region specific changes associated with brain diseases. Coupling recent technological advances in genomics with cell-type specific methodologies, we are presented with an unprecedented opportunity to better understand the genetics of normal brain development and function and, in turn, the molecular basis of neuropsychiatric disorders. In this review, we will outline ongoing efforts towards this goal and will discuss approaches with the potential to shed light on the mechanism(s) of action of cell-type specific cis regulatory elements and their putative roles in disease, with particular emphasis on understanding the manner in which the epigenome and CREs influence the etiology of SCZ. PMID- 26827159 TI - Techniques for assisting difficult delivery at caesarean section. AB - BACKGROUND: Caesarean section involves making an incision in the woman's abdomen and cutting through the uterine muscle. The baby is then delivered through that incision. Difficult caesarean birth may result in injury for the infant or complications for the mother. Methods to assist with delivery include vacuum or forceps extraction or manual delivery utilising fundal pressure. Medication that relaxes the uterus (tocolytic medication) may facilitate the birth of the baby at caesarean section. Delivery of the impacted head after prolonged obstructed labour can be associated with significant maternal and neonatal complication; to facilitate delivery of the head the surgeon may utilise either reverse breech extraction or head pushing. OBJECTIVES: To compare the use of tocolysis (routine or selective use) with no use of tocolysis or placebo and to compare different extraction methods at the time of caesarean section for outcomes of infant birth trauma, maternal complications (particularly postpartum haemorrhage requiring blood transfusion), and long-term measures of infant and childhood morbidity. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2015) and reference lists of retrieved studies. SELECTION CRITERIA: All published, unpublished, and ongoing randomised controlled trials comparing the use of tocolytic agents (routine or selective) at caesarean section versus no use of tocolytic or placebo at caesarean section to facilitate the birth of the baby. Use of instrument versus manual delivery to facilitate birth of the baby. Reverse breech extraction versus head pushing to facilitate delivery of the deeply impacted fetal head. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: Seven randomised controlled trials, involving 582 women undergoing caesarean section were included in this review. The risk of bias of included trials was variable, with some trials not adequately describing allocation or randomisation.Three comparisons were included. 1. Tocolysis versus no tocolysisA single randomised trial involving 97 women was identified and included in the review. Birth trauma was not reported. There were no cases of any maternal side-effect reported in either the nitroglycerin or the placebo group. No other maternal and infant health outcomes were reported. 2. Reverse breech extraction versus head push for the deeply impacted head at full dilation at caesarean section Four randomised trials involving 357 women were identified and included in the review. The primary outcome of birth trauma was reported by three trials and there was no difference between reverse breech extraction and head push for this rare outcome (three studies, 239 women, risk ratio (RR) 1.55, 95% confidence interval (CI) 0.42 to 5.73). Secondary outcomes including endometritis rate (three studies, 285 women, average RR 0.52, 95% CI 0.26 to 1.05, Tau I2 = 0.22, I2 = 56%), extension of uterine incision (four studies, 357 women, average RR 0.23, 95% CI 0.13 to 0.40), mean blood loss (three studies, 298 women, mean difference (MD) -294.92, 95% CI 493.25 to -96.59; I2 = 98%) and neonatal intensive care unit (NICU)/special care nursery (SCN) admission (two studies, 226 babies, average RR 0.53, 95% CI 0.23 to 1.22, Tau I2 = 0.27, I2 = 74%) were decreased with reverse breech extraction. No differences were observed between groups for many of the other secondary outcomes reported (blood loss > 500 mL; blood transfusion; wound infection; mean hospital stay; average Apgar score).There was significant heterogeneity between the trials for the outcomes mean blood loss, operative time and mean hospital stay, making comparison difficult. However the operation duration was significantly shorter for reverse breech extraction, which may correspond with ease of delivery and therefore, the amount of tissue trauma and therefore, significantly less blood loss. Given the heterogeneity, we cannot define the amount of difference in blood loss, operative time or hospital stay however. 3. Instrument (vacuum or forceps) versus manual extraction at elective caesarean section Two randomised trials involving 128 women were identified and included in the review. Only one trial reported maternal and infant health outcomes as prespecified in this review. This trial reported birth trauma as an outcome but there were no instances of birth trauma in either comparison group. There were no differences found in mean fall in haemoglobin (Hb) between groups (one study, 44 women, MD 0.03, 95% CI -0.53 to 0.59), or in uterine incision extension (one study, 44 women, RR 0.70, 95% CI 0.13 to 3.73). AUTHORS' CONCLUSIONS: There is currently insufficient information available from randomised trials to support or refute the routine or selective use of tocolytic agents or instrument to facilitate infant birth at the time of difficult caesarean section. There is limited evidence that reverse breech extraction may improve maternal and fetal outcomes, though there was no difference in primary outcome of infant birth trauma. Further randomised controlled trials are needed to answer these questions. PMID- 26827153 TI - Emotion dysregulation explains relations between sleep disturbance and smoking quit-related cognition and behavior. AB - Poor sleep quality and tobacco use are common and co-occurring problems, although the mechanisms underlying the relations between sleep disturbance and smoking are poorly understood. Sleep disturbance lowers odds of smoking cessation success and increases odds of relapse. One reason may be that sleep loss leads to emotion dysregulation, which in turn, leads to reductions in self-efficacy and quit related problems. To address this gap, the current study examined the explanatory role of emotion dysregulation in the association between sleep disturbance and smoking in terms of (1) self-efficacy for remaining abstinent in relapse situations, (2) the presence of a prior quit attempt greater than 24h, and (3) the experience of quit-related problems among 128 adults (Mage=40.2; SD=11.0; 52.3% female) seeking treatment for smoking cessation. Results suggested that increased levels of sleep disturbance are related to emotion dysregulation which, in turn, may lead to lower levels of self-efficacy for remaining abstinent, more quit-related problems, and being less likely to have had a quit attempt of 24h or greater. Further, these indirect effects were present above and beyond variance accounted for by theoretically-relevant covariates (e.g., gender and educational attainment), suggesting that they may maintain practical significance. These findings suggest that this malleable emotional risk factor (emotion dysregulation) could serve as a target for intervention among those with poor sleep and tobacco use. PMID- 26827161 TI - Synthesis and evaluation of 1,7-diheteroarylhepta-1,4,6-trien-3-ones as curcumin based anticancer agents. AB - Thirty (1E,4E,6E)-1,7-diaryl-1,4,6-heptatrien-3-ones, featuring a central linear trienone linker and two identical nitrogen-containing heteroaromatic rings, were designed and synthesized as curcumin-based anticancer agents on the basis of their structural similarity to the enol-tautomer of curcumin, in addition to taking advantage of the possibly enhanced pharmacokinetic profiles contributed by the basic nitrogen-containing heteroaromatic rings. Their cytotoxicity and antiproliferative activity were evaluated towards both androgen-dependent and androgen-independent prostate cancer cell lines, as well as HeLa human cervical cancer cells. Among them, the ten most potent analogues are 5- to 36-fold more potent than curcumin in inhibiting cancer cell proliferation. The acquired structure-activity relationship data indicate (i) that (1E,4E,6E)-1,7-diaryl 1,4,6-heptatrien-3-ones represent a potential scaffold for development of curcumin-based agents with substantially improved cytotoxicity and anti proliferative effect; and (ii) 1-alkyl-1H-imidazol-2-yl and 1-alkyl-1H benzo[d]imidazole-2-yl serve as optimal heteroaromatic rings for increased in vitro potency of this scaffold. Two of most potent compounds displayed no apparent cytotoxicity toward MCF-10A normal mammary epithelial cells at 1 MUM concentration. Treatment of PC-3 prostate cancer cells with the most potent compound led to appreciable cell cycle arrest at a G1/G0 phase and cell apoptosis induction. PMID- 26827157 TI - Giant conjunctival squamous cell carcinoma. Treatment with surgery following topical interferon alpha-2b. AB - CASE REPORT: A 50-year-old man presented with a giant and invasive mass at the nasal limbus in his right eye. A surgical excision without safety margins was promptly performed, followed by interferon alpha-2b (IFNalpha2b) eye drops. After monitoring the patient for two years and after performing a number of biopsies, he remains free from any signs of disease. DISCUSSION: For cases of giant and invasive squamous cell carcinoma, to reverse the order of treatment, by first performing an early tumour excision, followed by the application of topical IFNalpha2b, may prove useful to achieve total remission of the tumour. PMID- 26827163 TI - Functional dissociation between action and perception of object shape in developmental visual object agnosia. AB - According to the two visual systems model, the cortical visual system is segregated into a ventral pathway mediating object recognition, and a dorsal pathway mediating visuomotor control. In the present study we examined whether the visual control of action could develop normally even when visual perceptual abilities are compromised from early childhood onward. Using his fingers, LG, an individual with a rare developmental visual object agnosia, manually estimated (perceptual condition) the width of blocks that varied in width and length (but not in overall size), or simply picked them up across their width (grasping condition). LG's perceptual sensitivity to target width was profoundly impaired in the manual estimation task compared to matched controls. In contrast, the sensitivity to object shape during grasping, as measured by maximum grip aperture (MGA), the time to reach the MGA, the reaction time and the total movement time were all normal in LG. Further analysis, however, revealed that LG's sensitivity to object shape during grasping emerged at a later time stage during the movement compared to controls. Taken together, these results demonstrate a dissociation between action and perception of object shape, and also point to a distinction between different stages of the grasping movement, namely planning versus online control. Moreover, the present study implies that visuomotor abilities can develop normally even when perceptual abilities developed in a profoundly impaired fashion. PMID- 26827155 TI - Comparison of ankle kinematics and ground reaction forces between prospectively injured and uninjured collegiate cross country runners. AB - Biomechanical comparative studies on running-related injuries have included either currently or retrospectively injured runners. The purpose of this study was to prospectively compare ankle joint and ground reaction force variables between collegiate runners who developed injuries during the cross country season and those who did not. Running gait analyses using a motion capture system and force platform were conducted on 19 collegiate runners prior to the start of their cross country season. Ten runners sustained running-related injuries and 9 remained healthy during the course of the season. Strike index, peak loading rate of the vertical ground reaction force, dorsiflexion range of motion (ROM), eversion ROM, peak eversion angle, peak eversion velocity, and eversion duration from the start of the season were compared between injury groups. Ankle eversion ROM and peak eversion velocity were greater in uninjured runners while peak eversion angle was greater in injured runners. Greater ankle eversion ROM and eversion velocity with lower peak eversion angle may be beneficial in reducing injury risk in collegiate runners. The current data may only be applicable to collegiate cross country runners with similar training and racing schedules and threshold magnitudes of ankle kinematic variables to predict injury risk are still unknown. PMID- 26827167 TI - Surgical management and outcome of iatrogenic radial nerve injection injuries. AB - OBJECTIVE: Iatrogenic injury to the radial nerve can occur following intramuscular or intravenous injections of the upper extremity. In this study, we review the injury mechanism, operative techniques, and outcomes of patients evaluated for radial nerve injection injuries. METHODS: Data from 33 patients evaluated by the senior authors (DGK and DHK) from 1970-2011 with radial nerve injection injuries were reviewed retrospectively. All patients had injury of the nerve during injection. All corrective operations involved the use of direct intraoperative nerve action potential (NAP) recordings and either neurolysis, neurectomy, or suture/graft repair. The Louisiana State University Health Science (LSUHS) grading system was used for clinical assessment. RESULTS: Of the 33 patients, 23 underwent surgical intervention for persistent neurological deficit and/or pain. Of the 24 patients evaluated for injuries at the arm level, 17 required surgical exploration and repair for persistent symptoms. Nine patients required external neurolysis because the lesions were in continuity and positive NAP recording was across the lesion. All of these patients achieved a Grade 4 or better in functional recovery. Eight patients with lesions in continuity but in which NAP could not be recorded underwent either end-to-end suture (7) or graft repair (1) following resection of a 3.0 cm non-recordable segment. All patients achieved Grade 3 or 4 functional recovery. Six patients with forearm injuries involving the superficial sensory branch of radial nerve underwent either neurolysis (3) or neurectomy (3). CONCLUSIONS: Surgical exploration may be indicated when pain or disabling motor deficits persist. Early diagnosis and operative intervention can achieve favorable outcomes through exploration and radial nerve repair. PMID- 26827162 TI - Synthesis, evaluation and structure-activity relationship of new 3-carboxamide coumarins as FXIIa inhibitors. AB - Inhibitors of the coagulation factor XIIa (FXIIa) are attractive to detail the roles of this protease in hemostasis and thrombosis, to suppress artifact due to contact pathway activation in blood coagulation assays, and they are promising as antithrombotic therapy. The 3-carboxamide coumarins have been previously described as small-molecular-weight FXIIa inhibitors. In this study, we report a structure-activity relationship (SAR) study around this scaffold with the aim to discover new selective FXIIa inhibitors with an improved physico-chemical profile. To better understand these SAR, docking experiments were undertaken. For this purpose, we built an original hybrid model of FXIIa. This model has the advantage to gather the best features from the recently published crystal structure of FXIIa in its zymogen form and a more classical homology model. Results with the hybrid model are encouraging as they help understanding the activity and selectivity of our best compounds. PMID- 26827154 TI - Gambling transitions among adult gamblers: A multi-state model using a Markovian approach applied to the JEU cohort. AB - INTRODUCTION: The aim of this paper is to study transitions between two states of gambling in adulthood (problem gambling and non-problem gambling) and to identify factors that might influence these transitions. METHODS: Data for this 2-year long longitudinal study were collected in a French Outpatient Addiction Treatment Center, in gambling establishments and through the press. Both problem gamblers and non-problem gamblers were evaluated using a structured interview and self report questionnaires. The statistical analysis was carried out using a Markovian approach. RESULTS: The analyzed cohort consisted of 304 gamblers with 519 observed transitions. Participants with no past-year gambling problems (based on the DSM-IV) had a probability of about 90% of also having no past-year gambling problems at the following assessment, whereas the observed percentage of problem gamblers transitioning to non-problem gambling was of 48%. We reported (i) vulnerability factors of transitioning to problem gambling (such as an anxiety disorder or an Attention Deficit Hyperactivity Disorder (ADHD) during the childhood), (ii) protective factors for non-problem gamblers, (iii) recovery factors (such as ongoing treatment and younger age) and (iv) persistence factors of a gambling problem (such as a persistent ADHD). CONCLUSIONS: The status of problem gambler is unstable over time, whereas we found stability among non problem gamblers. Our findings suggest the existence of vulnerability and protective factors in gambling. These results lead to think about preventive actions and adaptive care, such as cognitive-behavioral therapy or researching gambling problems in people with an anxiety disorder or ADHD. PMID- 26827160 TI - Design, synthesis and biological evaluation of monobactams as antibacterial agents against gram-negative bacteria. AB - A series of monobactam derivatives were prepared and evaluated for their antibacterial activities against susceptible and resistant Gram-negative strains, taking Aztreonam and BAL30072 as the leads. Six conjugates (12a-f) bearing PIH like siderophore moieties were created to enhance the bactericidal activities against Gram-negative bacteria based on Trojan Horse strategy, and all of them displayed potencies against susceptible Gram-negative strains with MIC <= 8 MUg/mL. SAR revealed that the polar substituents on the oxime side chain were beneficial for activities against resistant Gram-negative bacteria. Compounds 19c and 33a-b exhibited the promising potencies against ESBLs-producing E. coli and Klebsiella pneumoniae with MICs ranging from 2 MUg/mL to 8 MUg/mL. These results offered powerful information for further strategic optimization in search of the antibacterial candidates against MDR Gram-negative bacteria. PMID- 26827171 TI - Transient pressure changes in the vertebral canal during whiplash motion--A hydrodynamic modeling approach. AB - In vehicle collisions, the occupant's torso is accelerated in a given direction while the unsupported head tends to lag behind. This mechanism results in whiplash motion to the neck. In whiplash experiments conducted for animals, pressure transients have been recorded in the spinal canal. It was hypothesized that the transients caused dorsal root ganglion dysfunction. Neck motion introduces volume changes inside the vertebral canal. The changes require an adaptation which is likely achieved by redistribution of blood volume in the internal vertebral venous plexus (IVVP). Pressure transients then arise from the rapid redistribution. The present study aimed to explore the hypothesis theoretically and analytically. Further, the objectives were to quantify the effect of the neck motion on the pressure generation and to identify the physical factors involved. We developed a hydrodynamic system of tubes that represent the IVVP and its lateral intervertebral vein connections. An analytical model was developed for an anatomical geometrical relation that the venous blood volume changes with respect to the vertebral angular displacement. This model was adopted in the hydrodynamic tube system so that the system can predict the pressure transients on the basis of the neck vertebral motion data from a whiplash experiment. The predicted pressure transients were in good agreement with the earlier experimental data. A parametric study was conducted and showed that the system can be used to assess the influences of anatomical geometrical properties and vehicle collision severity on the pressure generation. PMID- 26827164 TI - Environment and evolution modulate plant virus pathogenesis. AB - The study of plant viruses has focussed on those causing diseases in crops and, only recently, in wild plants. However, increasing evidence shows that plant viruses often are neutral, or even beneficial, for their hosts. Thus, plant viruses can be conditional mutualists, although the underlying mechanisms have been seldom analyzed. Little is known about what environmental factors modulate virus pathogenesis, and how. A major factor can be higher horizontal transmission rates in agricultural than in wild ecosystems. However, ecosystem simplification in human-managed habitats may result in changed epidemiological factors that influence pathogenesis. The interplay between ecology, evolution and pathogenesis awaits further research. PMID- 26827176 TI - A case study of energy transfer mechanism from uranium to europium in ZnAl3O4 spinel host by photoluminescence spectroscopy. AB - Zinc aluminate (ZAO), a member of spinel class of inorganic compounds has been of much interest of late due to its wide range of use in catalysis, optical, electronic and ceramic industries. When doped with several lanthanides, this material has proved to be a potential host matrix for phosphors. As lanthanides suffer from poor (direct) excitation and emission cross sections, the use of a co dopant ion can help to circumvent this and extract better emission from a lanthanide doped ZAO system. In this connection, energy transfer mechanism from uranium to europium in the ZAO host was investigated by photoluminescence spectroscopic technique. It was seen that uranium gets stabilized in the hexavalent state as UO6(6-) (octahedral uranate) where as the lanthanide ion, Eu is stabilized in its trivalent state in the ZAO host. In the co-doped system, an efficient energy transfer pathway from the uranate to europium ion was observed. Based upon emission and life time data a suitable mechanism was proposed for the energy transfer (quenching) process. It was proposed that after excitation by photons, the uranate ions transfer their energy to nearby (5)D1 level of Eu(3+) ions which non-radiatively de-excites to the corresponding lower levels of (5)D0. Further this (5)D0 level decays in a radiative mode to the (7)F manifold giving the characteristic emission profile of trivalent Eu. It was proposed that both static and dynamic types of energy transfer mechanism were responsible for this process. PMID- 26827173 TI - A micro-Raman spectroscopic investigation of leukemic U-937 cells in aged cultures. AB - Recently it has been shown that micro-Raman spectroscopy combined with multivariate analysis is able to discriminate among different types of tissues and tumoral cells by the detection of significant alterations and/or reorganizations of complex biological molecules, such as nucleic acids, lipids and proteins. Moreover, its use, being in principle a non-invasive technique, appears an interesting clinical tool for the evaluation of the therapeutical effects and of the disease progression. In this work we analyzed molecular changes in aged cultures of leukemia model U937 cells with respect to fresh cultures of the same cell line. In fact, structural variations of individual neoplastic cells on aging may lead to a heterogeneous data set, therefore falsifying confidence intervals, increasing error levels of analysis and consequently limiting the use of Raman spectroscopy analysis. We found that the observed morphological changes of U937 cells corresponded to well defined modifications of the Raman contributions in selected spectral regions, where markers of specific functional groups, useful to characterize the cell state, are present. A detailed subcellular analysis showed a change in cellular organization as a function of time, and correlated to a significant increase of apoptosis levels. Besides the aforementioned study, Raman spectra were used as input for principal component analysis (PCA) in order to detect and classify spectral changes among U937 cells. PMID- 26827172 TI - Markerless three-dimensional tracking of masticatory movement. AB - Conventional methods for measuring mandibular movement are expensive and require headgear and a marker attached to the mandibular incisors. These make assessment of normal chewing difficult. The aim of the present study was to test the validity of a markerless three-dimensional system for tracking masticatory movement by comparing it with a conventional method using an incisal marker. The study investigated 100 chewing cycles in 10 participants. The jaw tracking system consisted of a camera capable of recording depth and red, green, and blue data simultaneously, a laptop computer, and data analysis software. Depth data for each participant's face, tracked in real time, produced a computed 3D mask. The most prominent point of the soft tissue under the lip was defined as the chin point. A dental clasp cemented to the labial surface of the mandibular incisors was defined as the incisal point. The movement of these two measuring points was simultaneously recorded during mastication of chewing gum for 20s. To conduct the same analysis on each cycle from the two measuring points, all cycles were normalized by dividing by the corresponding vertical displacement because of their size variation. The findings showed excellent intramethod correlation for normalized horizontal displacement at every level (>0.9; except for 2 out of 19 levels; 0.896 and 0.898), and a lack of proportional bias. These findings suggest a correlation between the chewing cycles from two measuring points, the incisor and the chin, further suggesting the feasibility of a markerless system for tracking masticatory movement. PMID- 26827170 TI - Nitrate repletion strategy for enhancing lipid production from marine microalga Tetraselmis sp. AB - The cell growth rate and cellular lipid content of microalgae are affected by the nitrogen levels during cultivation. The growth rate and lipid content of marine microalga Tetraselmis sp. was found to increase under nitrate replete conditions, but not under deplete conditions. Thus, in order to enhance the lipid productivity of Tetraselmis sp., a two-stage culture process utilizing nitrate replete condition was applied. When the cells were cultivated in F/2 medium for five days in the first stage, the obtained lipid content and productivity were 22.4% and 26.7mgL(-1)d(-1), respectively. After second stage of cultivation for a further 36h under nitrate replete conditions with 8.82mM NaNO3, increased biomass concentration of 1.32gL(-1) and lipid content of 30.5% were obtained, with an enhanced lipid productivity of 47.3mgL(-1)d(-1). PMID- 26827169 TI - Efficient recovery of nitrate and phosphate from wastewater by an amine-grafted adsorbent for cyanobacterial biomass production. AB - Various types of wastewater have been widely utilized in microalgae and cyanobacteria cultivation for environmental and economic reasons. However, the problems of low cell growth and biomass contamination due to direct use of wastewater remain unresolved. In the present study, nitrate and phosphate were separated from wastewater by adsorption and subsequently used for cyanobacterial biomass production. To this end, an amine-grafted magnetic absorbent was synthesized. The synthesized absorbent recovered ca. 78% nitrate and 93% phosphate from wastewater. Regenerated medium was prepared using recovered nutrients as nitrogen and phosphate sources, which were efficiently assimilated by cyanobacterial culture. Compared to synthetic medium, there was no difference in growth and nutrient removal using regenerated medium. The proposed indirect method of wastewater utilization would prevent contamination of the produced biomass by unfavorable substances, which will broaden its potential applications. PMID- 26827175 TI - Temperature-dependent IR and Raman studies of metal-organic frameworks [(CH3)2NH2][M(HCOO)3], M=Mg and Cd. AB - Two metal-organic frameworks of [(CH3)2NH2][M(HCOO)3], where M=Mg and Cd, have been investigated by temperature-dependent IR and Raman methods in order to determine the nature of the phase transition. Our results indicate that phase transition in the Mg-compound is driven by ordering of the dimethylammonium cations. Additional X-ray diffraction and spectroscopic studies on Cd-compound as the function of temperature reveal that this compound does not undergo any structural phase transition. We attribute this behavior to the large size of the cavity occupied by the dimethylammonium cations and thus weak hydrogen bonding between these cations and formate ions. PMID- 26827165 TI - Selection of HIV vaccine candidates for concurrent testing in an efficacy trial. AB - Phase IIb or III HIV-1 vaccine efficacy trials are generally large and operationally challenging. To mitigate this challenge, the HIV Vaccine Trials Network is designing a Phase IIb efficacy trial accommodating the evaluation of multiple vaccine regimens concurrently. As this efficacy trial would evaluate a limited number of vaccine regimens, there is a need to develop a framework for optimizing the strategic selection of regimens from the large number of vaccine candidates tested in Phase I/IIa trials. In this paper we describe the approaches for the selection process, including the choice of immune response endpoints and the statistical criteria and algorithms. We illustrate the selection approaches using data from HIV-1 vaccine trials. PMID- 26827174 TI - Theoretical investigation on ESIPT mechanism of a new fluorescent sensor in different solvents. AB - In the present work, a new phenylbenzimidazole derivatized fluorescent sensor (L) (J. Lumin. 147 (2014) 179), has been investigated on the excited state proton transfer (ESPT) based on the time-dependent density functional theory (TDDFT) method. The calculated absorption and fluorescence spectra based on the TDDFT method are in agreement with the experimental results. Two kinds of structures of L chromophore are found in the first excited (S1) state, which may be due to the proton transfer reactive. Hydrogen bond strengthening has been testified in the S1 state based on comparing staple bond lengths and bond angles involved in hydrogen bonding between the S0 state and the S1 state. In addition, the calculated infrared spectra at the N-H stretching vibrational region and calculated hydrogen bond energy also declare the phenomenon of hydrogen bond strengthening. The frontier molecular orbitals (MOs) and Mulliken's charge distribution analysis method as well as natural bond orbital (NBO) demonstrate the charge distribution, which provides the tendency of ESIPT reaction. The potential energy surfaces of the S0 and S1 states are constructed to explain the mechanism of the proton transfer in the excited state in detail. In addition, the ESIPT process of sensor L is dependent on different solvents. PMID- 26827168 TI - Cost-effectiveness analysis of CTA and LP for evaluation of suspected SAH after negative non-contrast CT. AB - OBJECTIVES: Diagnostic workup of patients presenting with thunderclap headache and negative initial head CT remains a challenge, with most commonly employed strategies being lumbar puncture (LP) and CT angiography (CTA). The objective of this study was to determine the cost-effectiveness of these options. PATIENTS AND METHODS: A decision model was designed using clinical probabilities, costs, and utilities from published values in the literature. Base case analysis and Monte Carlo simulation were performed using the model to determine the cost effectiveness of both options. RESULTS: CTA was associated with an expected cost of $747 and an expected utility of 0.798603029. In comparison, LP was associated with a cost of $504 and an expected utility of 0.799259526, making it the optimal strategy from both the cost and the utility perspectives. LP was also the more cost-effective strategy in all iterations in the Monte Carlo simulation. A sensitivity analysis showed that with the 2014 US Medicare reimbursement values, LP would remain the more cost-effective strategy unless its cost exceeded 4 times its current value. CONCLUSION: LP should remain the preferred strategy for evaluation of SAH in patients presenting with thunderclap headache and negative non-contrast head CT. CTA is not an effective replacement, from either a utility or cost perspective. PMID- 26827166 TI - Ossified spinal meningiomas: Clinical and surgical features. AB - OBJECT: Meningiomas constitute 25% of primary spinal tumors and predominantly involve the thoracic spinal cord. Although calcifications are commonly seen in intracranial meningiomas, gross calcifications are observed in only 1-5% of all spinal meningiomas. We report the clinical findings, surgical strategy and histological features of 9 patients with ossified spinal meningiomas (OSMs). PATIENTS AND METHODS: Clinical and surgical features of 9 patients with ossified spinal meningiomas were retrospectively reviewed. RESULTS: There were 8 women and 1 man with a mean age of 59 years. In 7 patients, the lesions were localized in the thoracic segment of the spine while in 2 patients in the lower cervical segment. All patients presented with weakness of the lower limbs and hypoesthesia below the site level of the lesion. Only 2 patients presented with urinary incontinence. Gross-total resection of the tumor was achieved in 6 patients while in 3 a subtotal removal of the meningioma was obtained. In all patients the postoperative course was uneventful. Six patients presented with a significant neurological improvement while in 3 patients a mild improvement was observed. Microscopically, all tumors showed typical histological pattern of ossified meningioma. CONCLUSIONS: OSMs are amenable to surgery if the complete removal can be achieved. Because of their hard-rock consistency complete resection can be challenging. In difficult cases, subtotal removal can be advised and follow-up imaging is mandatory. Overall, the risk of long-term recurrence of the lesions is low, and a good clinical outcome after total or subtotal removal can be expected. PMID- 26827132 TI - Isolated Effects of Renal Failure, Anthropometric Indices, and Serum Total Iron Binding Capacity as Determinants of Muscle Performance in Hemodialysis Patients. AB - OBJECTIVE: We quantified the isolated impact of end-stage renal disease (ESRD) on physical performance under contemporary hemodialysis treatment independent of comorbid diseases, characterized principal anthropometric components, and adjusted for their influence and compared associations of C-reactive protein (CRP), albumin, and serum total iron-binding capacity (TIBC) with muscle function. DESIGN: A case-control cross-sectional study. SETTING: University medical hospital and outpatient hemodialysis units. SUBJECTS: Ninety prevalent hemodialysis patients without important comorbidities and 140 controls. MAIN OUTCOME MEASURES: Handgrip strength (HGS) and 10-repetition sit-to-stand time (STS-10). RESULTS: Principal component analysis revealed 3 representative anthropometric measures to be included in explanatory models of muscle performance additional to body height: lean body mass, fat mass, and joint size. Controlling for these covariates, age, sex, and residual comorbidity, ESRD was associated with a modest 7.5% reduction in HGS (B = -2.57 kg; 95% confidence interval: -4.81 to -0.39; P = .005; model R(2) 0.74) and a relatively larger prolongation of 27% in STS-10 time (B = 4s; 95% confidence interval: 2.61 to 5.4; P < .001; model R(2) 0.53). Lean body mass and height significantly predicted both tests, fat mass, and wrist size predicted HGS. In the subgroup of dialysis patients, only TIBC showed a significant association with HGS independently from age, sex, wrist size, whereas CRP and albumin did not. STS-10 time was not associated with any of these biomarkers. Results remained stable in sensitivity analyses excluding patients with reported chronic regional motor difficulties and aches. CONCLUSIONS: ESRD with contemporary hemodialysis therapy has a relatively modest negative comorbidity-free association with HGS and a larger effect on STS 10 lower extremity performance. Nonmodifiable anthropometric indices (body height and for HGS wrist size) have a significant independent impact and should be consistently adjusted for in future studies. In low-comorbidity dialysis patients, TIBC is a superior predictor of HGS compared with albumin and CRP. PMID- 26827177 TI - Simultaneous determination of benznidazole and itraconazole using spectrophotometry applied to the analysis of mixture: A tool for quality control in the development of formulations. AB - The aim of this work was the development of an analytical procedure using spectrophotometry for simultaneous determination of benznidazole (BNZ) and itraconazole (ITZ) in a medicine used for the treatment of Chagas disease. In order to achieve this goal, the analysis of mixtures was performed applying the Lambert-Beer law through the absorbances of BNZ and ITZ in the wavelengths 259 and 321 nm, respectively. Diverse tests were carried out for development and validation of the method, which proved to be selective, robust, linear, and precise. The lower limits of detection and quantification demonstrate its sensitivity to quantify small amounts of analytes, enabling its application for various analytical purposes, such as dissolution test and routine assays. In short, the quantification of BNZ and ITZ by analysis of mixtures had shown to be efficient and cost-effective alternative for determination of these drugs in a pharmaceutical dosage form. PMID- 26827179 TI - Extensive theoretical studies on the low-lying electronic states of BBr+. AB - The potential energy curves (PECs) of two lowest dissociation channels of BBr(+) have been thoroughly investigated using the internally contracted multireference configuration interaction method with Davidson correction and relativistic correction. All PECs are extrapolated to complete basis set limit. Several quasibound excited states caused by avoided crossings are found. Based on the PECs, the spectroscopic parameters of bound and quasibound states are obtained. The transition dipole moments and radiative lifetimes are predicted for all possible transitions. Finally, the spin-orbit coupling matrix elements are computed using the states interaction approach with the full Breit-Pauli Hamiltonian to analyze the interactions in PECs crossing regions. We propose that the 2(2)Sigma(+)-X(2)Sigma(+) and 2(2)Pi-X(2)Sigma(+) transitions which cannot be observed in experiments are attributed to the intricate couplings among 1(2)Pi, 2(2)Pi, 2(2)Sigma(+), 1(4)Sigma(+), 1(4)Delta, 1(4)Sigma(-), 1(2)Delta and 1(2)Sigma(-) states. PMID- 26827181 TI - Single Nucleotide Polymorphisms in MORC4, CD14, and TLR4 Are Related to Outcome of Allogeneic Stem Cell Transplantation. AB - BACKGROUND: Non-HLA genes may contribute to the prognosis after hematopoietic stem cell transplantation. We investigated associations between single nucleotide polymorphisms in regions of MORC4, CD14, TLR4, NOD2, SLC22A4, SLC22A5, CARD8, NLRP3, and CLDN2 and the outcomes of patients undergoing allogeneic stem cell transplantation. MATERIAL AND METHODS: Single nucleotide polymorphisms in selected regions were determined and analyzed for putative associations with overall mortality and acute graft-versus-host disease. Significant associations were further explored by logistic regression, controlling for additional variables. RESULTS: A significant association was identified between overall mortality among recipients and a nonsynonymous coding variant of MORC4 (rs6622126) in the recipient genetic makeup (P=0.029). Since MORC4 is located on the X-chromosome, the results were also analyzed separately for males and females. The association between overall mortality for recipients and the risk allele (rs6622126; A) was confirmed for males with respect to genetic makeup of recipients (P=0.012), donor genetic makeup (P=0.004), and the combined allele composition of the donor and recipient (P=0.001). A significant association was also identified between overall mortality and the recipient risk allele of CD14 (rs2569190; P=0.031), TLR4 (rs4986790; P=0.043), and NOD2 (carriage of at least 1 mutant allele of rs2066844, rs2066845, or rs2066847; P=0.048). Among the investigated genes, only the CD14 (rs2569190) recipient risk allele was significantly associated with acute graft-versus-host disease (P=0.023). Logistic regression models confirmed these findings, except for NOD2, and also identified a significant contribution by age at stem cell transplantation (MORC4, CD14, TLR4), diagnosis (CD14, TLR4), and prophylaxis (MORC4). CONCLUSIONS: Genetic variation in MORC4, CD14, and TLR4 may affect the outcome of allogeneic stem cell transplantation. PMID- 26827178 TI - Joint analyses model for total cholesterol and triglyceride in human serum with near-infrared spectroscopy. AB - The development of a small, dedicated near-infrared (NIR) spectrometer has promising potential applications, such as for joint analyses of total cholesterol (TC) and triglyceride (TG) in human serum for preventing and treating hyperlipidemia of a large population. The appropriate wavelength selection is a key technology for developing such a spectrometer. For this reason, a novel wavelength selection method, named the equidistant combination partial least squares (EC-PLS), was applied to the wavelength selection for the NIR analyses of TC and TG in human serum. A rigorous process based on the various divisions of calibration and prediction sets was performed to achieve modeling optimization with stability. By applying EC-PLS, a model set was developed, which consists of various models that were equivalent to the optimal model. The joint analyses model of the two indicators was further selected with only 50 wavelengths. The random validation samples excluded from the modeling process were used to validate the selected model. The root-mean-square errors, correlation coefficients and ratio of performance to deviation for the prediction were 0.197 mmol L(-1), 0.985 and 5.6 for TC, and 0.101 mmol L(-1), 0.992 and 8.0 for TG, respectively. The sensitivity and specificity for hyperlipidemia were 96.2% and 98.0%. These findings indicate high prediction accuracy and low model complexity. The proposed wavelength selection provided valuable references for the designing of a small, dedicated spectrometer for hyperlipidemia. The methodological framework and optimization algorithm are universal, such that they can be applied to other fields. PMID- 26827180 TI - Penalized discriminant analysis for the detection of wild-grown and cultivated Ganoderma lucidum using Fourier transform infrared spectroscopy. AB - An effective and simple analytical method using Fourier transform infrared (FTIR) spectroscopy to distinguish wild-grown high-quality Ganoderma lucidum (G. lucidum) from cultivated one is of essential importance for its quality assurance and medicinal value estimation. Commonly used chemical and analytical methods using full spectrum are not so effective for the detection and interpretation due to the complex system of the herbal medicine. In this study, two penalized discriminant analysis models, penalized linear discriminant analysis (PLDA) and elastic net (Elnet),using FTIR spectroscopy have been explored for the purpose of discrimination and interpretation. The classification performances of the two penalized models have been compared with two widely used multivariate methods, principal component discriminant analysis (PCDA) and partial least squares discriminant analysis (PLSDA). The Elnet model involving a combination of L1 and L2 norm penalties enabled an automatic selection of a small number of informative spectral absorption bands and gave an excellent classification accuracy of 99% for discrimination between spectra of wild-grown and cultivated G. lucidum. Its classification performance was superior to that of the PLDA model in a pure L1 setting and outperformed the PCDA and PLSDA models using full wavelength. The well-performed selection of informative spectral features leads to substantial reduction in model complexity and improvement of classification accuracy, and it is particularly helpful for the quantitative interpretations of the major chemical constituents of G. lucidum regarding its anti-cancer effects. PMID- 26827183 TI - Approaches for describing and communicating overall uncertainty in toxicity characterizations: U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) as a case study. AB - Single point estimates of human health hazard/toxicity values such as a reference dose (RfD) are generally used in chemical hazard and risk assessment programs for assessing potential risks associated with site- or use-specific exposures. The resulting point estimates are often used by risk managers for regulatory decision making, including standard setting, determination of emission controls, and mitigation of exposures to chemical substances. Risk managers, as well as stakeholders (interested and affected parties), often have limited information regarding assumptions and uncertainty factors in numerical estimates of both hazards and risks. Further, the use of different approaches for addressing uncertainty, which vary in transparency, can lead to a lack of confidence in the scientific underpinning of regulatory decision-making. The overarching goal of this paper, which was developed from an invited participant workshop, is to offer five approaches for presenting toxicity values in a transparent manner in order to improve the understanding, consideration, and informed use of uncertainty by risk assessors, risk managers, and stakeholders. The five approaches for improving the presentation and communication of uncertainty are described using U.S. Environmental Protection Agency's (EPA's) Integrated Risk Information System (IRIS) as a case study. These approaches will ensure transparency in the documentation, development, and use of toxicity values at EPA, the Agency for Toxic Substances and Disease Registry (ATSDR), and other similar assessment programs in the public and private sector. Further empirical testing will help to inform the approaches that will work best for specific audiences and situations. PMID- 26827188 TI - The trends of burns epidemiology in a tropical regional burns centre. AB - INTRODUCTION: Singapore General Hospital (SGH) is a regional burns centre in Southeast Asia and is the only dedicated burns facility providing specialized burns care in Singapore. METHODS: A cohort study was performed for burns patients admitted to SGH from 2011 to 2013. We compared our data with earlier studies and observed the trends of burns epidemiology in Singapore. Results were analyzed using the SPSS programme. RESULTS: 655 patients were admitted during this study period, a 35.9% increase from 2003 to 2005. Scalding by water and flame injury remain the top causes of burns and the mean extent of burn is 9.5%. TBSA correlates with the incidence of burn infection, bacteremia and mortality. Patients with >=20% TBSA are at a higher risk of bacteremia, and >= 34% TBSA is a predictor of mortality. 4.9% (n=32) of our patients developed bacteremia. Bacteremia was associated with a surgical duration of >=80min. Patients with bacteremia incurred longer hospitalization, and had higher mortality rates. Overall mortality rate of our burns patients has decreased from 4.5% to 2.7% (n=18). Key factors of mortality include inhalational injury, bacteremia and >=20% TBSA. CONCLUSION: This is a large epidemiology study of a tropical region burns centre. A total of 655 burns cases over a 3-year period were analyzed. We analysed the key factors associated with adverse outcomes including burns infection, bacteremia and mortality, factors associated with mortality, and discussed strategies on the optimization of burns care. PMID- 26827184 TI - Intake of phthalate-tainted foods and microalbuminuria in children: The 2011 Taiwan food scandal. AB - BACKGROUND: A major threat to public health involving phthalate-tainted foodstuffs occurred in Taiwan in 2011. Phthalates, mainly di-(2-ethylhexyl) phthalate (DEHP), were intentionally added to several categories of food commonly consumed by children. This study investigated the relationship between intake of the phthalate-tainted foods and renal function in children. METHODS: Children aged <=10years with possible phthalate exposure were enrolled in this study between August 2012 and January 2013. Questionnaires were used to collect details of exposure to phthalate-tainted foodstuffs, and blood and urine samples were collected for clinical biochemical workup. The clinical biomarkers of renal injury, including urinary microalbumin, N-acetyl-beta-d-glucosaminidase (NAG), and beta2-microglobulin were measured. Exposure was categorized based on recommended tolerable daily intake level defined by the U.S. Environmental Protection Agency (0.02mg/kg/day) and the European Food Safety Authority (0.05mg/kg/day). RESULTS: We analyzed intake and renal function of 184 children whose intake of DEHP-tainted foods was known. Higher DEHP exposure to DEHP tainted foods was significantly associated with increase of urine albumin/creatinine ratio (ACR). Children in the high-exposed group (daily DEHP intake (DDI)>0.05mg/kg/day) had 10.395 times the risk of microalbuminuria than the low-exposed group (DDI<=0.02 and >0mg/kg/day) and no-exposed group combined after adjustment (95% CI=1.096-98.580, P=0.04). CONCLUSION: Intake of DEHP from phthalate-tainted foods may be a potential risk factor for microalbuminuria, a marker of glomerular injury in children. PMID- 26827189 TI - Circulating levels of Th1 and Th2 chemokines in patients with ankylosing spondylitis. AB - OBJECTIVE: Although chemokines are critical elements for the selective attraction and activation of various leukocyte subsets in the inflammatory process, there are few findings concerning T helper (Th) 1 or Th2 chemokines in ankylosing spondylitis (AS). This study was designed to determine whether serum levels of chemokines that are preferentially chemotactic for Th1 (IFN-gamma-inducible protein-10, IP-10/CXCL10) and Th2 (thymus and activation regulated chemokine, TARC/CCL17) and (macrophage derived chemokine, MDC/CCL22) cells were elevated and whether they correlated with the clinical features in patients with AS. METHODS: Forty-two patients with axial AS and 25 healthy controls were enrolled into the study. Serum levels of chemokines (IP-10, TARC and MDC) and cytokines (IFN-gamma, TNF-alpha and IL-4) were examined using ELISA. The disease activity was evaluated by Ankylosing Spondylitis Disease Activity Score (ASDAS). Serum levels of IgG, IgA, IgM, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured. RESULTS: Serum chemokine levels of IP-10, TARC and MDC were significantly higher in patients with AS than those in healthy controls. Serum cytokine levels of IFN-gamma, TNF-alpha were also significantly increased, but the levels of IL-4 were not. Furthermore, IP-10 levels in AS patients correlated with ESP, CRP and ASDAS, while the levels of TARC and MDC did not correlate with these clinic indexes. Correlation analysis between the levels of chemokines and cytokines revealed a positive correlation between IP-10 and TNF-alpha. The levels of both Th1 and Th2 chemokines decreased under blockade of TNF-alpha. CONCLUSION: Our results suggest that both a Th1 chemoattractant IP-10 and Th2 chemoattractants, TARC and MDC, cooperatively play a role in the development of AS. PMID- 26827191 TI - Nurse leaders and the innovation competence gap. AB - BACKGROUND: Nurses are well-positioned for innovation in health care delivery, although innovation is not generally learned in formal educational programs. PURPOSE: The purpose of this study was to assess critical competencies for innovation success among nurse leaders in academia and practice, the perceived gaps on those competencies, and teaching methods that would be helpful in developing competencies related to innovation. METHOD: A Web-enabled descriptive survey design was used to capture nurse leaders' perceptions of important innovation competencies and how they assess their level of competence in the particular innovation domain. Preferred approaches for innovation pedagogy were also queried. DISCUSSION: Respondents indicated significant gaps in 18 of 19 innovation competencies. Implications are for inclusion of innovation competencies in formal and continuing nursing education. The most preferred innovation pedagogical approaches are case studies of failures and successes and project- and field-based approaches. Traditional lectures are the least preferred way to address innovation competency gaps. CONCLUSIONS: There is a significant gap in innovation competencies among nurse leaders in practice and academia. The way we teach innovation needs to involve closer collaboration between academia and practice. PMID- 26827193 TI - Communication: A simplified coupled-cluster Lagrangian for polarizable embedding. AB - A simplified coupled-cluster Lagrangian, which is linear in the Lagrangian multipliers, is proposed for the coupled-cluster treatment of a quantum mechanical system in a polarizable environment. In the simplified approach, the amplitude equations are decoupled from the Lagrangian multipliers and the energy obtained from the projected coupled-cluster equation corresponds to a stationary point of the Lagrangian. PMID- 26827195 TI - Communication: Rigidification of a lipid bilayer by an incorporated n-alkane. AB - Towards a greater understanding of the effects of organic molecules in biomembranes, the effects of a flexible alkyl chain on the morphologies of phospholipid vesicles are investigated. Vesicles composed of 1,2-dipalmitoyl-sn glycerol-3-phosphocholine and tetradecane (TD) rupture during cooling from the liquid-crystalline phase to the gel phase. A model calculation based on the size dependent rupture probability indicates that the bending rigidity of the bilayer in the gel phase is more than 10 times higher than that without TD, resulting in the rupture arising from elastic stress. The rigidification is caused by the denser molecular packing in the hydrophobic region by TD. There is little change of the rigidity in the liquid-crystalline phase. Additionally, the rigidification produces a characteristic morphology of the ternary giant vesicles including TD. Reported thermal behaviors imply that molecules with a linear and long alkyl chain, such as trans fatty acids, universally exhibit a similar effect, in contrast to rigid and bulky molecules, such as cholesterol. PMID- 26827192 TI - Perspectives of nursing faculty in Africa on global health nursing competencies. AB - BACKGROUND: It is important to define global health competencies for health professionals. To date, we know little about perspectives of nurses in Africa where environments are particularly challenging. PURPOSE: The purpose was to describe perceptions of nursing faculty in Africa about global health competencies and compare those to faculty from the Americas. METHODS: A 32-item online survey with a convenience sample of nursing faculty. RESULTS: Data from 63 nurses in 21 African countries and 618 in the Americas were analyzed. Competencies related to Social and Environmental Determinants of Health were awarded relatively higher scores. Competencies related to globalization of health and health care were ranked relatively lower. This was similar across regions. DISCUSSION: Nursing education should address the social implications for health. CONCLUSION: Participants in all three regions considered Social and Environmental Determinants of Health as a priority. These data help set educational priorities in a setting where educational and training resources are limited. PMID- 26827187 TI - Effect of transcranial direct current stimulation on pain anxiety during burn wound care. AB - BACKGROUND: Changes in neuronal activity by cathodal transcranial direct current stimulation (tDCS) of the sensory cortex can relieve acute pain. Studies have demonstrated high correlation between burn pain and anxiety in burn patients. The aim of this study was to assess the effect of tDCS on pain anxiety in patients with severe burn. METHODS: In a controlled randomized clinical trial, 60 subjects who were hospitalized during the year 2014 in the Department of Burn and Reconstructive Surgery of Imam Reza Hospital of Mashhad were selected as the sample for this study. The patients were randomly assigned to one of the two groups. A cathodal stimulation group that received real 1.0mA tDCS over sensory cortex lasted 20min and the control group received sham tDCS. Pain anxiety was obtained by self-report pain anxiety questionnaire before and after stimulation. It was also completed immediately after burn dressing. The data were analyzed by performing the Chi-square, Fisher's exact, independent samples t, paired samples t, Mann-Whitney and Wilcoxon tests using SPSS 11.5 software. RESULTS: Pain anxiety score reduced significantly in the real tDCS compared with sham group (23.4+/-3.8 versus 29.3+/-2.0, p<=0.001). After stimulation there was a decrease in pain anxiety score in real tDCS group (p=0.010). CONCLUSION: According to our study, cathodal cortical stimulation with tDCS is associated with significant reduction in pain anxiety in burn patients. PMID- 26827182 TI - GRADE: Assessing the quality of evidence in environmental and occupational health. AB - There is high demand in environmental health for adoption of a structured process that evaluates and integrates evidence while making decisions and recommendations transparent. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework holds promise to address this demand. For over a decade, GRADE has been applied successfully to areas of clinical medicine, public health, and health policy, but experience with GRADE in environmental and occupational health is just beginning. Environmental and occupational health questions focus on understanding whether an exposure is a potential health hazard or risk, assessing the exposure to understand the extent and magnitude of risk, and exploring interventions to mitigate exposure or risk. Although GRADE offers many advantages, including its flexibility and methodological rigor, there are features of the different sources of evidence used in environmental and occupational health that will require further consideration to assess the need for method refinement. An issue that requires particular attention is the evaluation and integration of evidence from human, animal, in vitro, and in silico (computer modeling) studies when determining whether an environmental factor represents a potential health hazard or risk. Assessment of the hazard of exposures can produce analyses for use in the GRADE evidence-to-decision (EtD) framework to inform risk-management decisions about removing harmful exposures or mitigating risks. The EtD framework allows for grading the strength of the recommendations based on judgments of the certainty in the evidence (also known as quality of the evidence), as well as other factors that inform recommendations such as social values and preferences, resource implications, and benefits. GRADE represents an untapped opportunity for environmental and occupational health to make evidence-based recommendations in a systematic and transparent manner. The objectives of this article are to provide an overview of GRADE, discuss GRADE's applicability to environmental health, and identify priority areas for method assessment and development. PMID- 26827194 TI - Communication: Temperature derivative of the dielectric constant gives access to multipoint correlations in polar liquids. AB - Fluctuations of the dipole moment of a macroscopic dielectric sample are induced by thermal motions. The variance of the sample dipole moment, characterizing the extent of thermal fluctuations, is a decaying function of temperature for many polar liquids. This result is inconsistent with the Nyquist (fluctuation dissipation) theorem predicting the variance of a macroscopic property to grow linearly with temperature. The reason for a qualitatively different behavior is in strong multi-particle correlations of dipolar orientations. An equation connecting the temperature slope of the dielectric constant to a static three point correlation function is derived. When applied to experimental data for polar and hydrogen-bonding liquids at normal conditions, the three-point correlations of different liquids fall on a single master curve as a function of the dielectric constant. Static three-point correlation functions can potentially reflect the growing spatial correlation length on approach to the glass transition. However, the measured temperature slope of the dielectric constant of glycerol does not indicate a change in such a lengthscale. PMID- 26827185 TI - Whatever happens to trauma patients who leave against medical advice? AB - BACKGROUND: Although trauma patients are frequently discharged against medical advice (AMA), the fate of these patients remains mostly unknown. METHODS: Patients with traumatic injuries were identified in the California State Inpatient Database, 2007 to 2011. Readmission characteristics of patients discharged AMA were compared with patients discharged home. RESULTS: There were 203,756 (75.65%) patients discharged home and 4,480 (1.66%) discharged AMA. Compared with those discharged home, patients discharged AMA had significantly higher 30-day readmission rates (17.12% vs 6.75%), rates of multiple readmissions (3.83% vs 1.12%), and likelihood of being readmitted at different hospitals (44.83% vs 33.82%) (all P < .001). The commonest reasons for readmission in patients discharged AMA were psychiatric conditions [adjusted odds ratio: 1.67 (1.21 to 2.27)]. CONCLUSIONS: Discharge AMA is associated with multiple readmissions and higher rates of readmissions at different hospitals. Early identification of vulnerable patients and improved modalities to prevent discharge AMA among these patients may reduce the negative outcomes associated with discharge AMA among trauma patients. PMID- 26827190 TI - [BK virus infections in kidney transplantation]. AB - BK virus is near ubiquitous, with a seroprevalence of around 80% in the general population. Subsequent to an asymptomatic primary infection, BK virus then remains dormant in healthy subjects. Reactivation occurs in immunocompromised people. BKv is pathogenic mainly among patients who have received a kidney transplant, in whom the virus can cause specific tubulo-interstitial nephritis and even result in graft failure among approximately 20 to 30% of nephritic cases. Since the mid 90 s, incidence has increased with the use of new powerful immunosuppressor treatments. The cornerstone of BK virus infection or BK virus associated nephropathy treatment is a decrease of the immunosuppressive regimen, which must then be offset with the risk of rejection. The use of several adjuvant therapies has been submitted (fluoroquinolones, leflunomide, intravenous immunoglobulins, cidofovir), with no sufficient proof enabling the recommendation of first-line prescription. The high frequency of this infection and its potential harmfulness argue for the use of prevention strategies, at least among patients presenting risk factors. Retransplantation is safe after a first kidney allograft loss caused by BK-virus nephropathy, on condition that a screening for viremia is frequently conducted. PMID- 26827197 TI - The distinguishable cluster approach from a screened Coulomb formalism. AB - The distinguishable cluster doubles equations have been derived starting from an effective screened Coulomb formalism and a particle-hole symmetric formulation of the Fock matrix. A perturbative triples correction to the distinguishable cluster with singles and doubles (DCSD) has been introduced employing the screened integrals. It is shown that the resulting DCSD(T) method is more accurate than DCSD for reaction energies and is less sensitive to the static correlation than coupled cluster with singles and doubles with a perturbative triples correction. PMID- 26827186 TI - Association of sentinel lymph node diameter with melanoma metastasis. AB - BACKGROUND: Lymph nodes are an important part of the immune system and the size of the lymph node reflects local immunologic activity. The purpose of this study was to examine the association between sentinel lymph node (SLN) size and the presence of nodal metastasis in patients with melanoma. METHODS: Retrospective review of a prospectively maintained database of patients undergoing SLN biopsy for cutaneous melanoma between February 1995 and January 2013. The maximum pathologic diameter and the volume of the largest node was used. A nodal diameter of 1.5 cm, included in 2 interquartile ranges of both positive and negative SLNs, was used as the cutoff for multivariate regression. RESULTS: Of 1,017 SLN biopsies, 826 (81%) had complete size measurements and were included in the analysis. Patients with a positive SLN were younger (median 50 vs 53 years, P = .032), had deeper primary lesions (2 vs 1.4 mm, P < .001), and had larger SLN volume (.8 vs .6 cc, P = .009) or maximum diameter (1.9 vs. 1.6 cm, P = .03). Sex, pathologic ulceration, mitosis, and the type or location of the primary was not statistically different. On multivariate analysis; age, depth of primary, and both SLN volume and maximum diameter remained significant. An SLN greater than 1.5 cm in maximum diameter has a 60% increased odds ratio of being positive after adjusting for age, sex, and depth of primary lesion (P = .046). CONCLUSIONS: Larger SLN maximum diameter is associated with nodal positivity independent of age, sex, depth of primary lesion, and location of SLN biopsy. The etiology and significance of larger SLNs warrant further analysis. PMID- 26827196 TI - Biased transport of Brownian particles in a weakly corrugated serpentine channel. AB - We investigate the biased transport of Brownian particles in a weakly corrugated channel with constant width but a varying centerline (called serpentine channel). Two different types of channels are considered: a soft-channel is confined by a potential energy landscape; a solid-channel is confined by solid walls. Based on the small amplitude of channel boundaries, the asymptotic method is used to analytically calculate two important macroscopic transport properties--average velocity (or mobility) and effective dispersion coefficient. We find the nonlinear dependence of transport properties on Peclet numbers, which is qualitatively different from the results in a narrow serpentine channel, in which the leading order terms of mobility and the effective dispersion coefficient do not depend on Peclet numbers. In the purely diffusive case where the Peclet number is zero, the Sutherland-Einstein relation is satisfied in both soft and solid channels. PMID- 26827200 TI - Exact two-component relativistic energy band theory and application. AB - An exact two-component (X2C) relativistic density functional theory in terms of atom-centered basis functions is proposed for relativistic calculations of band structures and structural properties of periodic systems containing heavy elements. Due to finite radial extensions of the local basis functions, the periodic calculation is very much the same as a molecular calculation, except only for an Ewald summation for the Coulomb potential of fluctuating periodic monopoles. For comparison, the nonrelativistic and spin-free X2C counterparts are also implemented in parallel. As a first and pilot application, the band gaps, lattice constants, cohesive energies, and bulk moduli of AgX (X = Cl, Br, I) are calculated to compare with other theoretical results. PMID- 26827202 TI - Stark-assisted quantum confinement of wavepackets. A coupling of nonadiabatic interaction and CW-laser. AB - When a nonadiabatic system that has an ionic state (large dipole moment) and a covalent state (small dipole moment) is located in a strong laser field, the crossing point of the two potential energy curves is forced to oscillate due to the oscillating laser field and to meet wavepackets moving on the potential curves many times. This leads to additional transitions between the two states, and under favorable conditions, the wavepacket may be confined in a spatial region rich in nonadiabatic interaction. In this paper, taking the LiF molecule system in a continuous-wave driving field as a prototypical example, the dynamical origins of the wavepacket confinement are theoretically investigated. PMID- 26827204 TI - Gauge-invariant expectation values of the energy of a molecule in an electromagnetic field. AB - In this paper, we show that the full Hamiltonian for a molecule in an electromagnetic field can be separated into a molecular Hamiltonian and a field Hamiltonian, both with gauge-invariant expectation values. The expectation value of the molecular Hamiltonian gives physically meaningful results for the energy of a molecule in a time-dependent applied field. In contrast, the usual partitioning of the full Hamiltonian into molecular and field terms introduces an arbitrary gauge-dependent potential into the molecular Hamiltonian and leaves a gauge-dependent form of the Hamiltonian for the field. With the usual partitioning of the Hamiltonian, this same problem of gauge dependence arises even in the absence of an applied field, as we show explicitly by considering a gauge transformation from zero applied field and zero external potentials to zero applied field, but non-zero external vector and scalar potentials. We resolve this problem and also remove the gauge dependence from the Hamiltonian for a molecule in a non-zero applied field and from the field Hamiltonian, by repartitioning the full Hamiltonian. It is possible to remove the gauge dependence because the interaction of the molecular charges with the gauge potential cancels identically with a gauge-dependent term in the usual form of the field Hamiltonian. We treat the electromagnetic field classically and treat the molecule quantum mechanically, but nonrelativistically. Our derivation starts from the Lagrangian for a set of charged particles and an electromagnetic field, with the particle coordinates, the vector potential, the scalar potential, and their time derivatives treated as the variables in the Lagrangian. We construct the full Hamiltonian using a Lagrange multiplier method originally suggested by Dirac, partition this Hamiltonian into a molecular term Hm and a field term Hf, and show that both Hm and Hf have gauge-independent expectation values. Any gauge may be chosen for the calculations; but following our partitioning, the expectation values of the molecular Hamiltonian are identical to those obtained directly in the Coulomb gauge. As a corollary of this result, the power absorbed by a molecule from a time-dependent, applied electromagnetic field is equal to the time derivative of the non-adiabatic term in the molecular energy, in any gauge. PMID- 26827203 TI - Iterative quantum-classical path integral with dynamically consistent state hopping. AB - We investigate the convergence of iterative quantum-classical path integral calculations in sluggish environments strongly coupled to a quantum system. The number of classical trajectories, thus the computational cost, grows rapidly (exponentially, unless filtering techniques are employed) with the memory length included in the calculation. We argue that the choice of the (single) trajectory branch during the time preceding the memory interval can significantly affect the memory length required for convergence. At short times, the trajectory branch associated with the reactant state improves convergence by eliminating spurious memory. We also introduce an instantaneous population-based probabilistic scheme which introduces state-to-state hops in the retained pre-memory trajectory branch, and which is designed to choose primarily the trajectory branch associated with the reactant at early times, but to favor the product state more as the reaction progresses to completion. Test calculations show that the dynamically consistent state hopping scheme leads to accelerated convergence and a dramatic reduction of computational effort. PMID- 26827201 TI - Exact vs. asymptotic spectral densities in the Garg-Onuchic-Ambegaokar charge transfer model and its effect on Fermi's golden rule rate constants. AB - The Garg-Onuchic-Ambegaokar model [J. Chem. Phys. 83, 4491 (1985)] has been used extensively for benchmarking methods aimed at calculating charge transfer rates. Within this model, the donor and acceptor diabats are described as shifted parabolas along a single primary mode, which is bilinearly coupled to a harmonic bath consisting of secondary modes, characterized by an Ohmic spectral density with exponential cutoff. Rate calculations for this model are often performed in the normal mode representation, with the corresponding effective spectral density given by an asymptotic expression derived at the limit where the Ohmic bath cutoff frequency is much larger than the primary mode frequency. We compare Fermi's golden rule rate constants obtained with the asymptotic and exact effective spectral densities. We find significant deviations between rate constants obtained from the asymptotic spectral density and those obtained from the exact one in the deep inverted region. Within the range of primary mode frequencies commonly employed, we find that the discrepancies increase with decreasing temperature and with decreasing primary mode frequency. PMID- 26827199 TI - Constructing diabatic representations using adiabatic and approximate diabatic data--Coping with diabolical singularities. AB - We have recently introduced a diabatization scheme, which simultaneously fits and diabatizes adiabatic ab initio electronic wave functions, Zhu and Yarkony J. Chem. Phys. 140, 024112 (2014). The algorithm uses derivative couplings in the defining equations for the diabatic Hamiltonian, H(d), and fits all its matrix elements simultaneously to adiabatic state data. This procedure ultimately provides an accurate, quantifiably diabatic, representation of the adiabatic electronic structure data. However, optimizing the large number of nonlinear parameters in the basis functions and adjusting the number and kind of basis functions from which the fit is built, which provide the essential flexibility, has proved challenging. In this work, we introduce a procedure that combines adiabatic state and diabatic state data to efficiently optimize the nonlinear parameters and basis function expansion. Further, we consider using direct properties based diabatizations to initialize the fitting procedure. To address this issue, we introduce a systematic method for eliminating the debilitating (diabolical) singularities in the defining equations of properties based diabatizations. We exploit the observation that if approximate diabatic data are available, the commonly used approach of fitting each matrix element of H(d) individually provides a starting point (seed) from which convergence of the full H(d) construction algorithm is rapid. The optimization of nonlinear parameters and basis functions and the elimination of debilitating singularities are, respectively, illustrated using the 1,2,3,4(1)A states of phenol and the 1,2(1)A states of NH3, states which are coupled by conical intersections. PMID- 26827208 TI - A generalized Poisson solver for first-principles device simulations. AB - Electronic structure calculations of atomistic systems based on density functional theory involve solving the Poisson equation. In this paper, we present a plane-wave based algorithm for solving the generalized Poisson equation subject to periodic or homogeneous Neumann conditions on the boundaries of the simulation cell and Dirichlet type conditions imposed at arbitrary subdomains. In this way, source, drain, and gate voltages can be imposed across atomistic models of electronic devices. Dirichlet conditions are enforced as constraints in a variational framework giving rise to a saddle point problem. The resulting system of equations is then solved using a stationary iterative method in which the generalized Poisson operator is preconditioned with the standard Laplace operator. The solver can make use of any sufficiently smooth function modelling the dielectric constant, including density dependent dielectric continuum models. For all the boundary conditions, consistent derivatives are available and molecular dynamics simulations can be performed. The convergence behaviour of the scheme is investigated and its capabilities are demonstrated. PMID- 26827209 TI - SCAN-based hybrid and double-hybrid density functionals from models without fitted parameters. AB - By incorporating the nonempirical strongly constrained and appropriately normed (SCAN) semilocal density functional [J. Sun, A. Ruzsinszky, and J. P. Perdew, Phys. Rev. Lett. 115, 036402 (2015)] in the underlying expression of four existing hybrid and double-hybrid models, we propose one hybrid (SCAN0) and three double-hybrid (SCAN0-DH, SCAN-QIDH, and SCAN0-2) density functionals, which are free from any fitted parameters. The SCAN-based double-hybrid functionals consistently outperform their parent SCAN semilocal functional for self interaction problems and noncovalent interactions. In particular, SCAN0-2, which includes about 79% of Hartree-Fock exchange and 50% of second-order Moller Plesset correlation, is shown to be reliably accurate for a very diverse range of applications, such as thermochemistry, kinetics, noncovalent interactions, and self-interaction problems. PMID- 26827205 TI - Energy transfer in structured and unstructured environments: Master equations beyond the Born-Markov approximations. AB - We explore excitonic energy transfer dynamics in a molecular dimer system coupled to both structured and unstructured oscillator environments. By extending the reaction coordinate master equation technique developed by Iles-Smith et al. [Phys. Rev. A 90, 032114 (2014)], we go beyond the commonly used Born-Markov approximations to incorporate system-environment correlations and the resultant non-Markovian dynamical effects. We obtain energy transfer dynamics for both underdamped and overdamped oscillator environments that are in perfect agreement with the numerical hierarchical equations of motion over a wide range of parameters. Furthermore, we show that the Zusman equations, which may be obtained in a semiclassical limit of the reaction coordinate model, are often incapable of describing the correct dynamical behaviour. This demonstrates the necessity of properly accounting for quantum correlations generated between the system and its environment when the Born-Markov approximations no longer hold. Finally, we apply the reaction coordinate formalism to the case of a structured environment comprising of both underdamped (i.e., sharply peaked) and overdamped (broad) components simultaneously. We find that though an enhancement of the dimer energy transfer rate can be obtained when compared to an unstructured environment, its magnitude is rather sensitive to both the dimer-peak resonance conditions and the relative strengths of the underdamped and overdamped contributions. PMID- 26827206 TI - Linked coupled cluster Monte Carlo. AB - We consider a new formulation of the stochastic coupled cluster method in terms of the similarity transformed Hamiltonian. We show that improvement in the granularity with which the wavefunction is represented results in a reduction in the critical population required to correctly sample the wavefunction for a range of systems and excitation levels and hence leads to a substantial reduction in the computational cost. This development has the potential to substantially extend the range of the method, enabling it to be used to treat larger systems with excitation levels not easily accessible with conventional deterministic methods. PMID- 26827207 TI - Overcoming potential energy distortions in constrained internal coordinate molecular dynamics simulations. AB - The Internal Coordinate Molecular Dynamics (ICMD) method is an attractive molecular dynamics (MD) method for studying the dynamics of bonded systems such as proteins and polymers. It offers a simple venue for coarsening the dynamics model of a system at multiple hierarchical levels. For example, large scale protein dynamics can be studied using torsional dynamics, where large domains or helical structures can be treated as rigid bodies and the loops connecting them as flexible torsions. ICMD with such a dynamic model of the protein, combined with enhanced conformational sampling method such as temperature replica exchange, allows the sampling of large scale domain motion involving high energy barrier transitions. Once these large scale conformational transitions are sampled, all-torsion, or even all-atom, MD simulations can be carried out for the low energy conformations sampled via coarse grained ICMD to calculate the energetics of distinct conformations. Such hierarchical MD simulations can be carried out with standard all-atom forcefields without the need for compromising on the accuracy of the forces. Using constraints to treat bond lengths and bond angles as rigid can, however, distort the potential energy landscape of the system and reduce the number of dihedral transitions as well as conformational sampling. We present here a two-part solution to overcome such distortions of the potential energy landscape with ICMD models. To alleviate the intrinsic distortion that stems from the reduced phase space in torsional MD, we use the Fixman compensating potential. To additionally alleviate the extrinsic distortion that arises from the coupling between the dihedral angles and bond angles within a force field, we propose a hybrid ICMD method that allows the selective relaxing of bond angles. This hybrid ICMD method bridges the gap between all-atom MD and torsional MD. We demonstrate with examples that these methods together offer a solution to eliminate the potential energy distortions encountered in constrained ICMD simulations of peptide molecules. PMID- 26827210 TI - Determination of ground and excited state dipole moments via electronic Stark spectroscopy: 5-methoxyindole. AB - The dipole moments of the ground and lowest electronically excited singlet state of 5-methoxyindole have been determined by means of optical Stark spectroscopy in a molecular beam. The resulting spectra arise from a superposition of different field configurations, one with the static electric field almost parallel to the polarization of the exciting laser radiation, the other nearly perpendicular. Each field configuration leads to different intensities in the rovibronic spectrum. With an automated evolutionary algorithm approach, the spectra can be fit and the ratio of both field configurations can be determined. A simultaneous fit of two spectra with both field configurations improved the precision of the dipole moment determination by a factor of two. We find a reduction of the absolute dipole moment from 1.59(3) D to 1.14(6) D upon electronic excitation to the lowest electronically excited singlet state. At the same time, the dipole moment orientation rotates by 54(?) showing the importance of the determination of the dipole moment components. The dipole moment in the electronic ground state can approximately be obtained from a vector addition of the indole and the methoxy group dipole moments. However, in the electronically excited state, vector addition completely fails to describe the observed dipole moment. Several reasons for this behavior are discussed. PMID- 26827198 TI - Transform-limited-pulse representation of excitation with natural incoherent light. AB - The excitation of molecular systems by natural incoherent light relevant, for example, to photosynthetic light-harvesting is examined. We show that the result of linear excitation with natural incoherent light can be obtained using incident light described in terms of transform limited pulses, as opposed to conventional classical representations with explicit random character. The derived expressions allow for computations to be done directly for any thermal light spectrum using a simple wave function formalism and provide a route to the experimental determination of natural incoherent excitation using pulsed laser techniques. Pulses associated with solar and cosmic microwave background radiation are provided as examples. PMID- 26827211 TI - Controlling the high frequency response of H2 by ultra-short tailored laser pulses: A time-dependent configuration interaction study. AB - We combine the stochastic pulse optimization (SPO) scheme with the time-dependent configuration interaction singles method in order to control the high frequency response of a simple molecular model system to a tailored femtosecond laser pulse. For this purpose, we use H2 treated in the fixed nuclei approximation. The SPO scheme, as similar genetic algorithms, is especially suited to control highly non-linear processes, which we consider here in the context of high harmonic generation. Here, we will demonstrate that SPO can be used to realize a "non harmonic" response of H2 to a laser pulse. Specifically, we will show how adding low intensity side frequencies to the dominant carrier frequency of the laser pulse and stochastically optimizing their contribution can create a high frequency spectral signal of significant intensity, not harmonic to the carrier frequency. At the same time, it is possible to suppress the harmonic signals in the same spectral region, although the carrier frequency is kept dominant during the optimization. PMID- 26827215 TI - Molecular anions of polydeprotonated naphthalenes: An investigation on the metastability and deprotonation energies using nuclear-charge stabilization method. AB - The dianions and trianions of doubly- and triply-deprotonated naphthalenes are investigated using density functional theory (DFT) computations employing hybrid, long-range, and dispersion corrected exchange-correlation functionals. The investigated polyanionic species are found to be metastable with negative electron affinity and are further treated using a nuclear-charge stabilization method. The tunneling lifetimes of these anionic species were estimated to be a few femtoseconds. Notably, the deprotonated energies (DPEs) of naphthalene leading to the formation of triply deprotonated trianions are observed to be affected by the metastability of the dianions and trianions. For the deprotonation of doubly deprotonated dianions, the DPE calculated using the improved methodology based on the stabilization method is found to be nearly 100 kcal/mol more than that computed using the conventional procedure. Though the various DFT approximations employed are in a good agreement for predicting the lifetimes of the metastable species but in the prediction of electron-affinities and deprotonation energies, the dispersion-corrected DFT-D3 significantly disagrees with the long-range corrected DFT methods employing cam-B3LYP and omegaB97XD exchange-correlation functionals. PMID- 26827214 TI - Double photoionization of halogenated benzene. AB - We have experimentally investigated the double-photoionization process in C6BrF5 using monochromatized synchrotron radiation. We compare our results with previously published data for partially deuterated benzene (C6H3D3) over a wide range of photon energies from threshold to 270 eV. A broad resonance in the ratio of doubly to singly charged parent ions at about 65 eV appears shifted in energy compared to benzene data. This shift is due to the difference in the bond lengths in two molecules. A simple model can explain the shape of this resonance. At higher photon energies, we observe another broad resonance that can be explained as a second harmonic of the first resonance. PMID- 26827212 TI - Reaction rate constant for radiative association of CF(.). AB - Reaction rate constants and cross sections are computed for the radiative association of carbon cations (C(+)) and fluorine atoms (F) in their ground states. We consider reactions through the electronic transition 1(1)Pi -> X(1)Sigma(+) and rovibrational transitions on the X(1)Sigma(+) and a(3)Pi potentials. Semiclassical and classical methods are used for the direct contribution and Breit-Wigner theory for the resonance contribution. Quantum mechanical perturbation theory is used for comparison. A modified formulation of the classical method applicable to permanent dipoles of unequally charged reactants is implemented. The total rate constant is fitted to the Arrhenius Kooij formula in five temperature intervals with a relative difference of <3%. The fit parameters will be added to the online database KIDA. For a temperature of 10-250 K, the rate constant is about 10(-21) cm(3) s(-1), rising toward 10( 16) cm(3) s(-1) for a temperature of 30,000 K. PMID- 26827213 TI - Electronic spectra of 2- and 3-tolunitrile in the gas phase. I. A study of methyl group internal rotation via rovibronically resolved spectroscopy. AB - Rotationally resolved fluorescence excitation spectra of the origin bands in the S1 <- S0 transition of 2-tolunitrile (2TN) and 3-tolunitrile (3TN) have been recorded in the collision-free environment of a molecular beam. Analyses of these data provide the rotational constants of each molecule and the potential energy curves governing the internal rotation of the attached methyl groups in both electronic states. 2TN exhibits much larger barriers along this coordinate than 3TN. Interestingly, the electronic transition dipole moment in both molecules is markedly influenced by the position of the attached methyl group rather than the position of the cyano group; possible reasons for this intriguing behavior are discussed. PMID- 26827217 TI - High-level theoretical rovibrational spectroscopy beyond fc-CCSD(T): The C3 molecule. AB - An accurate local (near-equilibrium) potential energy surface (PES) is reported for the C3 molecule in its electronic ground state (X(1)Sigmag (+)). Special care has been taken in the convergence of the potential relative to high-order correlation effects, core-valence correlation, basis set size, and scalar relativity. Based on the aforementioned PES, several rovibrational states of all (12)C and (13)C substituted isotopologues have been investigated, and spectroscopic parameters based on term energies up to J = 30 have been calculated. Available experimental vibrational term energies are reproduced to better than 1 cm(-1) and rotational constants show relative errors of not more than 0.01%. The equilibrium bond length has been determined in a mixed experimental/theoretical approach to be 1.294 07(10) A in excellent agreement with the ab initio composite value of 1.293 97 A. Theoretical band intensities based on a newly developed electric dipole moment function also suggest that the infrared active (1, 1(1), 0)<-(0, 0(0), 0) combination band might be observable by high-resolution spectroscopy. PMID- 26827216 TI - Microwave measurements of the tropolone-formic acid doubly hydrogen bonded dimer. AB - The microwave spectrum was measured for the doubly hydrogen bonded dimer formed between tropolone and formic acid. The predicted symmetry of this dimer was C2v(M), and it was expected that the concerted proton tunneling motion would be observed. After measuring 25 a- and b-type rotational transitions, no splittings which could be associated with a concerted double proton tunneling motion were observed. The calculated barrier to the proton tunneling motion is near 15,000 cm(-1), which would likely make the tunneling frequencies too small to observe in the microwave spectra. The rotational and centrifugal distortion constants determined from the measured transitions were A = 2180.7186(98) MHz, B = 470.873 90(25) MHz, C = 387.689 84(22) MHz, DJ = 0.0100(14) kHz, DJK = 0.102(28) kHz, and DK = 13.2(81) kHz. The B3LYP/aug-cc-pVTZ calculated rotational constants were within 1% of the experimentally determined values. PMID- 26827218 TI - Absorption spectroscopy of heavy alkaline earth metals Ba and Sr in rare gas matrices--CCSD(T) calculations and atomic site occupancies. AB - Isolation of the heavier alkaline earth metals Ba and Sr in the solid rare gases (RGs) Ar, Kr, and Xe is analysed with absorption spectroscopy and interpreted partly with the assistance of ab initio calculations of the diatomic M ? RG ground state interaction potentials. The y(1)P <- a(1)S resonance transitions in the visible spectral region are used to compare the isolation conditions of these two metal atom systems and calcium. Complex absorption bands were recorded in all three metal atom systems even after extensive sample annealing. Coupled cluster calculations conducted on the ground states of the nine M ? RG diatomics (M = Ca, Sr, and Ba; RG = Ar, Kr, and Xe) at the coupled cluster single, double, and non iterative triple level of theory revealed long bond lengths (>5 A) and shallow bound regions (<130 cm(-1)). All of the M ? RG diatomics have bond lengths considerably longer than those of the rare gas dimers, with the consequence that isolation of these metal atoms in a single substitutional site of the solid rare gas is unlikely, with the possible exception of Ca/Xe. The luminescence of metal dimer bands has been recorded for Ba and Sr revealing very different behaviours. Resonance fluorescence with a lifetime of 15 ns is observed for the lowest energy transition of Sr2 while this transition is quenched in Ba2. This behaviour is consistent with the absence of vibrational structure on the dimer absorption band in Ba2 indicating lifetime broadening arising from efficient relaxation to low lying molecular states. More extensive 2D excitation-emission data recorded for the complex site structures present on the absorption bands of the atomic Ba and Sr systems will be presented in future publications. PMID- 26827220 TI - Molecular simulations and density functional theory calculations of bromine in clathrate hydrate phases. AB - Bromine forms a tetragonal clathrate hydrate structure (TS-I) very rarely observed in clathrate hydrates of other guest substances. The detailed structure, energetics, and dynamics of Br2 and Cl2 in TS-I and cubic structure I (CS-I) clathrate hydrates are studied in this work using molecular dynamics and quantum chemical calculations. X-ray diffraction studies show that the halogen-water oxygen distances in the cages of these structures are shorter than the sum of the van der Waals radii of halogen and oxygen atoms. This suggests that the stabilizing effects of halogen bonding or other non-covalent interactions (NCIs) may contribute to the formation of the unique tetragonal bromine hydrate structure. We performed molecular dynamics simulations of Br2 and Cl2 clathrate hydrates using our previously developed five-site charge models for the dihalogen molecules [Dureckova et al. Can. J. Chem. 93, 864 (2015)] which reproduce the computed electrostatic potentials of the dihalogens and account for the electropositive sigma-hole of the halogen bond donor (the dihalogen). Analysis of the radial distribution functions, enthalpies of encapsulation, velocity and orientation autocorrelation functions, and polar angle distributions are carried out for Br2 and Cl2 guests in various cages to contrast the properties of these guests in the TS-I and CS-I phases. Quantum chemical partial geometry optimizations of Br2 and Cl2 guests in the hydrate cages using the M06-2X functional give short halogen-water distances compatible with values observed in X-ray diffraction experiments. NCI plots of guest-cage structures are generated to qualitatively show the relative strength of the non-bonding interactions between dihalogens and water molecules. The differences between behaviors of Br2 and Cl2 guests in the hydrate cages may explain why bromine forms the unique TS-I phase. PMID- 26827222 TI - Impact of reduced symmetry on magnetic anisotropy of a single iron phthalocyanine molecule on a Cu substrate. AB - We study the magnetic anisotropy of a single iron phthalocyanine (FePc) molecule on a Cu(110) (2 * 1)-O by using inelastic electron tunneling spectroscopy (IETS) with low-temperature scanning tunneling microscopy. Two inelastic excitations derived from the splitting of the molecular triplet spin state appear as two pairs of steps symmetrically with respect to zero sample voltage. We measured IETS spectra with external magnetic fields perpendicular and parallel to the molecular plane, and we analyzed the spectral evolution with the effective spin Hamiltonian approach. We determined all parameters related with magnetic anisotropy at a single-molecule level, both the easy- and hard-magnetization directions, zero-field splitting constant, D = - 4.0 meV and E = 1.1 meV, the Lande g-tensor gxx, gyy, gzz=(1.82, 2.02, 2.34), and the constant of spin-orbit coupling lambda = - 19.1 meV. We stress that the symmetry breaking caused by the adsorption of FePc on the oxidized Cu(110) significantly impacts the magnetic anisotropy. PMID- 26827219 TI - Rotational and angular distributions of NO products from NO-Rg (Rg = He, Ne, Ar) complex photodissociation. AB - We present the results of an investigation into the rotational and angular distributions of the NO A state fragment following photodissociation of the NO He, NO-Ne, and NO-Ar van der Waals complexes excited via the A <- X transition. For each complex, the dissociation is probed for several values of Ea, the available energy above the dissociation threshold. For NO-He, the Ea values probed were 59, 172, and 273 cm(-1); for NO-Ne they were 50 and 166 cm(-1); and for NO-Ar they were 44, 94, 194, and 423 cm(-1). The NO A state rotational distributions arising from NO-He are cold, with most products in low angular momentum states. NO-Ne leads to broader NO rotational distributions but they do not extend to the maximum possible given the energy available. In the case of NO Ar, the distributions extend to the maximum allowed at that energy and show the unusual shapes associated with the rotational rainbow effect reported in previous studies. This is the only complex for which a rotational rainbow effect is observed at the chosen Ea values. Product angular distributions have also been measured for the NO A photodissociation product for the three complexes. NO-He produces nearly isotropic fragments, but the anisotropy parameter, beta, for NO Ne and NO-Ar photofragments shows a surprising change in sign from negative to positive as Ea increases within the unstructured excitation profile. Franck Condon selection of a broader distribution of geometries including more linear geometries at lower excitation energies and more T-shaped geometries at higher energies can account for the changing recoil anisotropy. Two-dimensional wavepacket calculations are reported to model the rotational state distributions and the bound-continuum absorption spectra. PMID- 26827225 TI - CO adsorption on small Aun (n = 1-4) structures supported on hematite. I. Adsorption on iron terminated alpha-Fe2O3 (0001) surface. AB - This is the first of two papers dealing with the adsorption of Au and formation of Aun nanostructures (n = 1-4) on hematite (0001) surface and adsorption of CO thereon. The stoichiometric Fe-terminated (0001) surface of hematite was investigated using density functional theory in the generalized gradient approximation of Perdew-Burke-Ernzerhof (PBE) form with Hubbard correction U, accounting for strong electron correlations (PBE+U). The structural, energetic, and electronic properties of the systems studied were examined for vertical and flattened configurations of Aun nanostructures adsorbed on the hematite surfaces. The flattened ones, which can be viewed as bilayer-like structures, were found energetically more favored than vertical ones. For both classes of structures the adsorption binding energy increases with the number of Au atoms in a structure. The adsorption of Aun induces charge rearrangement at the Aun/oxide contact which is reflected in work function changes. In most considered cases Aun adsorption increases the work function. A detailed analysis of the bonding electron charge is presented and the corresponding electron charge rearrangements at the contacts were quantified by a Bader charge analyses. The interaction of a CO molecule with the Aun nanostructures supported on alpha-Fe2O3 (0001) and the oxide support was studied. It is found that the CO adsorption binding to the hematite supported Aun structures is more than twice as strong as to the bare hematite surface. Analysis of the Bader charges on the atoms showed that in each case CO binds to the most positively charged (cationic) atom of the Aun structure. Changes in the electronic structure of the Aun species and of the oxide support, and their consequences for the interactions with CO, are discussed. PMID- 26827224 TI - Nonequilibrium study of the intrinsic free-energy profile across a liquid-vapour interface. AB - We calculate an atomistically detailed free-energy profile across a heterogeneous system using a nonequilibrium approach. The path-integral formulation of Crooks fluctuation theorem is used in conjunction with the intrinsic sampling method to calculate the free-energy profile for the liquid-vapour interface of the Lennard Jones fluid. Free-energy barriers are found corresponding to the atomic layering in the liquid phase as well as a barrier associated with the presence of an adsorbed layer as revealed by the intrinsic density profile. Our findings are in agreement with profiles calculated using Widom's potential distribution theorem applied to both the average and the intrinsic profiles as well as the literature values for the excess chemical potential. PMID- 26827223 TI - Methane dissociation on Pt(111): Searching for a specific reaction parameter density functional. AB - The theoretical description of methane dissociating on metal surfaces is a current frontier in the field of gas-surface dynamics. Dynamical models that aim at achieving a highly accurate description of this reaction rely on potential energy surfaces based on density functional theory calculations at the generalized gradient approximation. We focus here on the effect that the exchange correlation functional has on the reactivity of methane on a metal surface, using CHD3 + Pt(111) as a test case. We present new ab initio molecular dynamics calculations performed with various density functionals, looking also at functionals that account for the van der Waals (vdW) interaction. While searching for a semi-empirical specific reaction parameter density functional for this system, we find that the use of a weighted average of the PBE and the RPBE exchange functionals together with a vdW-corrected correlation functional leads to an improved agreement with quantum state-resolved experimental data for the sticking probability, compared to previous PBE calculations. With this semi empirical density functional, we have also investigated the surface temperature dependence of the methane dissociation reaction and the influence of the rotational alignment on the reactivity, and compared our results with experiments. PMID- 26827226 TI - CO adsorption on small Aun (n = 1-4) structures supported on hematite. II. Adsorption on the O-rich termination of alpha-Fe2O3(0001) surface. AB - The adsorption of small Aun (n = 1-4) nanostructures on oxygen terminated alpha Fe2O3(0001) surface was investigated using density functional theory in the generalized gradient approximation of Perdew-Burke-Ernzerhof (PBE) form with Hubbard correction U, accounting for strong electron correlations (PBE+U). The structural, energetic, and electronic properties were examined for two classes of the adsorbed Aun nanostructures with vertical and flattened configurations. Similarly to the Fe-terminated alpha-Fe2O3(0001) surface considered in Part I, the flattened configurations were found energetically more favored than vertical ones. The binding of Aun to the O-terminated surface is much stronger than to the Fe-termination. The adsorption bonding energy of Aun and the work function of the Aun/alpha-Fe2O3(0001) systems decrease with the increased number of Au atoms in a structure. All of the adsorbed Aun structures are positively charged. The bonding of CO molecules to the Aun structures is distinctly stronger than on the Fe terminated surface; however, it is weaker than the binding to the bare O terminated surface. The CO molecule binds to the Aun/alpha-Fe2O3(0001) system through a peripheral Au atom partly detached from the Aun structure. The results of this work indicate that the most energetically favored sites for adsorption of a CO molecule on the Aun/alpha-Fe2O3(0001) systems are atoms in the Au(0.5+) oxidation state. PMID- 26827227 TI - CO oxidation on Pt(111) at near ambient pressures. AB - The oxidation of CO on Pt(111) was investigated simultaneously by near ambient pressure X-ray photoelectron spectroscopy and online gas analysis. Different CO:O2 reaction mixtures at total pressures of up to 1 mbar were used in continuous flow mode to obtain an understanding of the surface chemistry. By temperature-programmed and by isothermal measurements, the onset temperature of the reaction was determined for the different reactant mixtures. Highest turnover frequencies were found for the stoichiometric mixture. At elevated temperatures, the reaction becomes diffusion-limited in both temperature-programmed and isothermal measurements. In the highly active regime, no adsorbates were detected on the surface; it is therefore concluded that the catalyst surface is in a metallic state, within the detection limits of the experiment, under the applied conditions. Minor bulk impurities such as silicon were observed to influence the reaction up to total inhibition by formation of non-platinum oxides. PMID- 26827221 TI - Response of complex networks to compression: Ca, La, and Y aluminoborosilicate glasses formed from liquids at 1 to 3 GPa pressures. AB - Aluminoborosilicate glasses containing relatively high field strength modifiers (Ca, La, and Y) have been compressed at pressures up to 3 GPa and near the glass transition temperature (Tg) and quenched to room temperature at high pressure followed by decompression. Structural changes were quantified with high resolution (27)Al and (11)B MAS nuclear magnetic resonance at 14.1-18.8 T. The changes with pressure in Al and B coordinations in the recovered samples are quite large with more than 50% decreases in tetrahedral aluminum ((IV)Al) and 200%-300% increases in tetrahedral boron ((IV)B). Glasses with higher field strength modifiers (La and Y) contain more high coordinated aluminum ((V,V I)Al) at all pressures studied. More high coordinated boron also correlates with higher field strength modifier if all three compositions are compared on an isothermal basis. Although lowering fictive temperature and increasing pressure both increase Al and B coordinations, our study shows that the actual mechanisms for structural changes are most probably different for temperature and pressure effects. Using a rough thermodynamic model to extrapolate to higher pressures, it appears that a simple non-bridging oxygen (NBO) consumption mechanism is not sufficient to convert all the aluminum to octahedral and boron to tetrahedral coordination, suggesting other mechanisms for structural changes could occur at high pressure as NBO becomes depleted. PMID- 26827230 TI - Determination of the critical micelle concentration in simulations of surfactant systems. AB - Alternative methods for determining the critical micelle concentration (cmc) are investigated using canonical and grand canonical Monte Carlo simulations of a lattice surfactant model. A common measure of the cmc is the "free" (unassociated) surfactant concentration in the presence of micellar aggregates. Many prior simulations of micellizing systems have observed a decrease in the free surfactant concentration with overall surfactant loading for both ionic and nonionic surfactants, contrary to theoretical expectations from mass-action models of aggregation. In the present study, we investigate a simple lattice nonionic surfactant model in implicit solvent, for which highly reproducible simulations are possible in both the canonical (NVT) and grand canonical (MUVT) ensembles. We confirm the previously observed decrease of free surfactant concentration at higher overall loadings and propose an algorithm for the precise calculation of the excluded volume and effective concentration of unassociated surfactant molecules in the accessible volume of the solution. We find that the cmc can be obtained by correcting the free surfactant concentration for volume exclusion effects resulting from the presence of micellar aggregates. We also develop an improved method for determination of the cmc based on the maximum in curvature for the osmotic pressure curve determined from MUVT simulations. Excellent agreement in cmc and other micellar properties between NVT and MUVT simulations of different system sizes is observed. The methodological developments in this work are broadly applicable to simulations of aggregating systems using any type of surfactant model (atomistic/coarse grained) or solvent description (explicit/implicit). PMID- 26827232 TI - Erratum: "Going beyond 'no-pair relativistic quantum chemistry'" [J. Chem. Phys. 139, 014108 (2013)]. PMID- 26827228 TI - Super-Maxwellian helium evaporation from pure and salty water. AB - Helium atoms evaporate from pure water and salty solutions in super-Maxwellian speed distributions, as observed experimentally and modeled theoretically. The experiments are performed by monitoring the velocities of dissolved He atoms that evaporate from microjets of pure water at 252 K and 4-8.5 molal LiCl and LiBr at 232-252 K. The average He atom energies exceed the flux-weighted Maxwell Boltzmann average of 2RT by 30% for pure water and 70% for 8.5m LiBr. Classical molecular dynamics simulations closely reproduce the observed speed distributions and provide microscopic insight into the forces that eject the He atoms from solution. Comparisons of the density profile and He kinetic energies across the water-vacuum interface indicate that the He atoms are accelerated by He-water collisions within the top 1-2 layers of the liquid. We also find that the average He atom kinetic energy scales with the free energy of solvation of this sparingly soluble gas. This free-energy difference reflects the steeply decreasing potential of mean force on the He atoms in the interfacial region, whose gradient is the repulsive force that tends to expel the atoms. The accompanying sharp decrease in water density suppresses the He-water collisions that would otherwise maintain a Maxwell-Boltzmann distribution, allowing the He atom to escape at high energies. Helium is especially affected by this reduction in collisions because its weak interactions make energy transfer inefficient. PMID- 26827229 TI - Computational study of pressure-driven methane transport in hierarchical nanostructured porous carbons. AB - Using the reflecting particle method together with a perturbation-relaxation loop developed in our previous work, we studied pressure-driven methane transport in hierarchical nanostructured porous carbons (HNPCs) containing both mesopores and micropores in non-equilibrium molecular dynamics simulations. The surface morphology of the mesopore wall was systematically varied by tuning interaction strength between carbon atoms and the template in a mimetic nanocasting process. Effects of temperature and mesopore size on methane transport in HNPCs were also studied. Our study shows that increased mesopore wall surface roughness changes the character of the gas-wall interaction from specular to diffuse, while the gas gas interaction is diminished due to the decrease of adsorption density. Effects of the mesopore wall surface morphology are the most significant at low temperatures and in small channels. Our systematic study provides a better understanding of the transport mechanisms of light gases through carbon nanotube composite membranes in experiments. PMID- 26827233 TI - The long spine board does not reduce lateral motion during transport--a randomized healthy volunteer crossover trial. AB - OBJECTIVE: For thirty years, emergency medical services agencies have emphasized limiting spinal motion during transport of the trauma patient to the emergency department. The long spine board (LSB) has been the mainstay of spinal motion restriction practices, despite the paucity of data to support its use. The purpose of this study was to determine reduction in lateral motion afforded by the LSB in comparison to the stretcher mattress alone. METHODS: This was a randomized controlled crossover trial where healthy volunteer subjects were randomly assigned to either LSB or stretcher mattress only. All subjects were fitted with a rigid cervical collar, secured to the assigned device (including foam head blocks), and driven on a closed course with prescribed turns at a low speed (<20 mph). Upon completion, the subjects were then secured to the other device and the course was repeated. Each subject was fitted with 3 graduated paper disks (head, chest, hip). Lasers were affixed to a scaffold attached to the stretcher bridging over the patient and aimed at the center of the concentric graduations on the disks. During transport, the degree of lateral movement was recorded during each turn. Significance was determined by t test. RESULTS: In both groups, the head demonstrated the least motion with 0.46+/-0.4-cm mattress and 0.97+/-0.7-cm LSB (P<= .0001). The chest and hip had lateral movement with chest 1.22+/-0.9-cm mattress and 2.22+/-1.4-cm LSB (P<= .0001), and the hip 1.20+/-0.9-cm mattress and 1.88+/-1.2-cm LSB (P<= .0001), respectively. In addition, lateral movement had a significant direct correlation with body mass index. CONCLUSION: The stretcher mattress significantly reduced lateral movement during transport. PMID- 26827236 TI - OGDD (Olive Genetic Diversity Database): a microsatellite markers' genotypes database of worldwide olive trees for cultivar identification and virgin olive oil traceability. AB - Olive (Olea europaea), whose importance is mainly due to nutritional and health features, is one of the most economically significant oil-producing trees in the Mediterranean region. Unfortunately, the increasing market demand towards virgin olive oil could often result in its adulteration with less expensive oils, which is a serious problem for the public and quality control evaluators of virgin olive oil. Therefore, to avoid frauds, olive cultivar identification and virgin olive oil authentication have become a major issue for the producers and consumers of quality control in the olive chain. Presently, genetic traceability using SSR is the cost effective and powerful marker technique that can be employed to resolve such problems. However, to identify an unknown monovarietal virgin olive oil cultivar, a reference system has become necessary. Thus, an Olive Genetic Diversity Database (OGDD) (http://www.bioinfo-cbs.org/ogdd/) is presented in this work. It is a genetic, morphologic and chemical database of worldwide olive tree and oil having a double function. In fact, besides being a reference system generated for the identification of unkown olive or virgin olive oil cultivars based on their microsatellite allele size(s), it provides users additional morphological and chemical information for each identified cultivar. Currently, OGDD is designed to enable users to easily retrieve and visualize biologically important information (SSR markers, and olive tree and oil characteristics of about 200 cultivars worldwide) using a set of efficient query interfaces and analysis tools. It can be accessed through a web service from any modern programming language using a simple hypertext transfer protocol call. The web site is implemented in java, JavaScript, PHP, HTML and Apache with all major browsers supported. Database URL: http://www.bioinfo-cbs.org/ogdd/. PMID- 26827235 TI - Recurrence and Survival Outcomes After Percutaneous Thermal Ablation of Oligometastatic Melanoma. AB - OBJECTIVES: To evaluate focal treatment of melanoma metastases and to explore whether any potential extended survival benefit exists in a select patient population. PATIENTS AND METHODS: All patients who underwent image-guided local thermal ablation of metastatic melanoma over an 11-year period (January 1, 2002, to December 31, 2013) were retrospectively identified using an internally maintained clinical registry. Only patients with oligometastatic stage IV disease amenable to complete ablation of all clinical disease at the time of ablation were included in the analysis. Overall survival and median progression-free survival periods were calculated. RESULTS: Thirty-three patients with primary ocular or nonocular melanoma had 66 metastases treated in the lungs, liver, bones, or soft tissues. Eleven (33%) patients were on systemic medical therapy at the time of the procedure. The median survival time was 3.8 years (range, 0.5 10.5 years), with a 4-year estimated survival of 44.1% (95% CI, 28%-68%). Local recurrence at the ablation site developed in 15.1% (5 of 33) of the patients and 13.6% of the tumors (9 of 66). The median progression-free survival time was 4.4 months (95% CI, 1.4 months to 10.5 years), with an estimated 1-year progression free survival of 30.3% (95% CI, 18%-51%). A subgroup analysis identified 11 patients with primary ocular melanoma and 22 with nonocular melanoma, with a median survival time of 3.9 years (range, 0.9-4.7 years) and 3.8 years (range, 0.5-10.5 years), respectively (P=.58). There were no major complications and no deaths within 30 days of the procedure. CONCLUSION: Selective use of image-guided thermal ablation of oligometastatic melanoma may provide results similar to surgical resection in terms of technical effectiveness and oncologic outcomes with minimal risk. PMID- 26827234 TI - Clinical trials in EDs: some suggestions. PMID- 26827231 TI - Partial wrapping and spontaneous endocytosis of spherical nanoparticles by tensionless lipid membranes. AB - Computer simulations of an implicit-solvent particle-based model are performed to investigate the interactions between small spherical nanoparticles and tensionless lipid bilayers. We found that nanoparticles are either unbound, wrapped by the bilayer, or endocytosed. The degree of wrapping increases with increasing the adhesion strength. The transition adhesion strength between the unbound and partially wrapped states decreases as the nanoparticle diameter is increased. We also observed that the transition adhesion strength between the wrapped states and endocytosis state decreases with increasing the nanoparticle diameter. The partial wrapping of the nanoparticles by the tensionless bilayer is explained by an elastic theory which accounts for the fact that the interaction between the nanoparticle and the bilayer extends beyond the contact region. The theory predicts that for small nanoparticles, the wrapping angle increases continuously with increasing the adhesion strength. However, for relatively large nanoparticles, the wrapping angle exhibits a discontinuity between weakly and strongly wrapped states. The size of the gap in the wrapping angle between the weakly wrapped and strongly wrapped states increases with decreasing the range of nanoparticle-bilayer interaction. PMID- 26827239 TI - Response to Dr. Rutten's comment on "Serum magnesium and not vitamin D is associated with better QoL in COPD: A cross-sectional study". PMID- 26827240 TI - Adaptive Servo Ventilation for Central Sleep Apnea: More Data, Please. PMID- 26827238 TI - Evaluation of therapeutic effect of omega-6 linoleic acid and thymoquinone enriched extracts from Nigella sativa oil in the mitigation of lipidemic oxidative stress in rats. AB - OBJECTIVE: Nigella sativa belongs to the Ranunculaceae family. The therapeutic role of methanolic extract (ME) and volatile oil (VO) fractionated from N. sativa seed oil was investigated for antiperoxidative and antioxidant effects in atherogenic suspension fed rats. METHODS: We examined the protective effects of ME and VO on the enzymatic and nonenzymatic antioxidants status in erythrocytes and the livers of atherogenic suspension fed rats. As a marker of lipid peroxidation, we estimated the conjugated diene, lipid hydroperoxide, and malondialdehyde concentrations in plasma in the following groups of rats: normolipidemic control, hyperlipidemic control, hyperlipidemic methanolic extract, and hyperlipidemic volatile oil. ME 500 mg or VO 100 mg/kg body weight of male rat was orally administrated for 30 d. RESULTS: Pretreatment of hyperlipidemic rats with these test extracts resulted in a significant decrease (P < 0.001) in the level of lipid peroxidation markers, conjugated diene, lipid hydroperoxide, and malondialdehyde (16-50%) compared to the hyperlipidemic control rats. In addition, ME and VO significantly (P < 0.001) elevated the hepatic and erythrocyte superoxide dismutase, catalase, and glutathione reductase activities (19-58%) compared to the hyperlipidemic rats. In liver homogenate of hyperlipidemic-ME and hyperlipidemic-VO, the glutathione-S-transferase activity was protected by 93% and 89%, and in erythrocytes, the glutathione peroxidase activity was protected by 90% and 77%, respectively. Interestingly, reduced glutathione level and activities of ATPases were protected to near normal levels. Pretreatment of rats with the test extracts replenished effectively (P < 0.001) the plasma total antioxidant power by an average of 88% against free radicals. CONCLUSIONS: The lipidemic oxidative stress was effectively mitigated by antiperoxidative activities of ME and VO. Thus, these test extracts, especially ME, may be used as antioxidant as well as hypolipidemic agents in the form of natural food supplement to prevent or treat diseases caused by free radicals. PMID- 26827237 TI - DOMMINO 2.0: integrating structurally resolved protein-, RNA-, and DNA-mediated macromolecular interactions. AB - Macromolecular interactions are formed between proteins, DNA and RNA molecules. Being a principle building block in macromolecular assemblies and pathways, the interactions underlie most of cellular functions. Malfunctioning of macromolecular interactions is also linked to a number of diseases. Structural knowledge of the macromolecular interaction allows one to understand the interaction's mechanism, determine its functional implications and characterize the effects of genetic variations, such as single nucleotide polymorphisms, on the interaction. Unfortunately, until now the interactions mediated by different types of macromolecules, e.g. protein-protein interactions or protein-DNA interactions, are collected into individual and unrelated structural databases. This presents a significant obstacle in the analysis of macromolecular interactions. For instance, the homogeneous structural interaction databases prevent scientists from studying structural interactions of different types but occurring in the same macromolecular complex. Here, we introduce DOMMINO 2.0, a structural Database Of Macro-Molecular INteractiOns. Compared to DOMMINO 1.0, a comprehensive database on protein-protein interactions, DOMMINO 2.0 includes the interactions between all three basic types of macromolecules extracted from PDB files. DOMMINO 2.0 is automatically updated on a weekly basis. It currently includes ~1,040,000 interactions between two polypeptide subunits (e.g. domains, peptides, termini and interdomain linkers), ~43,000 RNA-mediated interactions, and ~12,000 DNA-mediated interactions. All protein structures in the database are annotated using SCOP and SUPERFAMILY family annotation. As a result, protein mediated interactions involving protein domains, interdomain linkers, C- and N- termini, and peptides are identified. Our database provides an intuitive web interface, allowing one to investigate interactions at three different resolution levels: whole subunit network, binary interaction and interaction interface. Database URL: http://dommino.org. PMID- 26827243 TI - NICE guidance on panobinostat for patients with multiple myeloma after at least two previous treatments. PMID- 26827241 TI - Increased serum IgA concentration and plasmablast frequency in patients with age related macular degeneration. AB - Age-related macular degeneration (AMD) is the leading cause of blindness among senior citizens of developed countries, with currently unknown etiology. Despite the close associations between AMD development and inhibitory complement factor H mutations, the first step of complement activation, which is the antibody response in AMD patients, has not been studied. Here, we obtained blood and tear samples from AMD patients and Non-AMD controls. We found that compared to Non-AMD controls, AMD subjects had increased IgA titers in serum and tear, and had elevated levels of circulating antibody-secreting plasmablasts. The increase in antibody titer was limited to the IgA isotype, since no significant differences were observed in IgM and IgG isotypes between AMD patients and Non-AMD controls. Interestingly, this increased antibody response in AMD patients was correlated with disease severity, as late AMD patients had increased IgA titers in serum and tear, as well as elevated plasmablast frequency after staphylococcal enterotoxin B stimulation, compared to early AMD patients. Together, our results implicated a role of overreactive IgA responses in AMD pathogenesis. PMID- 26827242 TI - NICE guidance on radium-223 dichloride for hormone-relapsed prostate cancer with bone metastases. PMID- 26827245 TI - Survey of research activity among multidisciplinary health professionals. AB - Objective The aim of the present study was to describe the research activities being undertaken by health service employees within one Australian health service and explore their experiences with undertaking research. Methods The present mixed-methods study was conducted across one health service in Queensland, Australia, and included a cross-sectional online survey and interviews with healthcare service employees. The anonymous survey was a self-administered online questionnaire, distributed to all 6121 employees at the health service via email, asking about research activity and engagement. Willing participants were also interviewed on their perceptions and experiences with research and capacity building. Results In all, 151 participants responded to the survey and 22 participated in interviews. Three-quarters of respondents reported actively participating in research over the past 6 years and several research outputs, such as publications, conference presentations and competitive grant funding, were displayed. Four concepts emerged from interview findings, namely collaborative partnerships, skilled mentorship, embedding research and organisational support, which represented the overall theme 'opportunities for a research-infused health service'. Conclusion Employees of the health service recognised the importance of research and had a range of research skills, knowledge and experience. They also identified several opportunities for building research capacity in this service. What is known about the topic? Building research capacity among healthcare professionals is important for enabling the conduct of high-quality research in healthcare institutions. However, building research capacity is complex and influenced by the uniqueness of organisational context. In order to successfully build research capacity among employees at any health service, current research activity, skills and experience, as well as staff perceptions around building research capacity in that setting, should first be explored. What does this paper add? Healthcare services should incorporate teaching and research with clinical care to optimise outcomes for consumers. Support for research can be diminished in favour of clinical care and reduced emphasis on the importance of research can negatively influence research activity and expansion of clinician-led research. Highlighting the perceptions and experience of clinicians with enabling research and capacity building is a context-specific but necessary process to ensure that strategies, processes and resources are targeted to maintain support for research activity while overcoming barriers. What are the implications for practitioners? Participants in this study identified several ways to build research capacity in their health service, many of which may be applicable to other settings and contexts. Building research collaborations and academic partnerships are important to enable and drive research. Structural processes, such as organisational support and opportunities for skilled mentorship, may be necessary to build health service employees' research knowledge, skills and confidence. Finally, embedding research into everyday practice is important to foster a positive research culture within health services. PMID- 26827244 TI - NICE guidance on olaparib for maintenance treatment of patients with relapsed, platinum-sensitive, BRCA mutation-positive ovarian cancer. PMID- 26827247 TI - High-Resolution DNA Melting Analysis in Plant Research. AB - Genetic and genomic studies provide valuable insight into the inheritance, structure, organization, and function of genes. The knowledge gained from the analysis of plant genes is beneficial to all aspects of plant research, including crop improvement. New methods and tools are continually being developed to facilitate rapid and accurate mapping, sequencing, and analyzing of genes. Here, I review the recent progress in the application of high-resolution melting (HRM) analysis of DNA, a method that allows detecting polymorphism in double-stranded DNA by comparing profiles of melting curves. Use of HRM has expanded considerably in the past few years as the method was successfully applied for high-throughput genotyping, mapping genes, testing food products and seeds, and other areas of plant research. PMID- 26827251 TI - Prevention of depression worldwide: a wake-up call. PMID- 26827246 TI - Understanding COPD: A vision on phenotypes, comorbidities and treatment approach. AB - Chronic Obstructive Pulmonary Disease (COPD) phenotypes have become increasingly recognized as important for grouping patients with similar presentation and/or behavior, within the heterogeneity of the disease. The primary aim of identifying phenotypes is to provide patients with the best health care possible, tailoring the therapeutic approach to each patient. However, the identification of specific phenotypes has been hindered by several factors such as which specific attributes are relevant, which discriminant features should be used for assigning patients to specific phenotypes, and how relevant are they to the therapeutic approach, prognostic and clinical outcome. Moreover, the definition of phenotype is still not consensual. Comorbidities, risk factors, modifiable risk factors and disease severity, although not phenotypes, have impact across all COPD phenotypes. Although there are some identified phenotypes that are fairly consensual, many others have been proposed, but currently lack validation. The on-going debate about which instruments and tests should be used in the identification and definition of phenotypes has contributed to this uncertainty. In this paper, the authors review present knowledge regarding COPD phenotyping, discuss the role of phenotypes and comorbidities on the severity of COPD, propose new phenotypes and suggest a phenotype-based pharmacological therapeutic approach. The authors conclude that a patient-tailored treatment approach, which takes into account each patient's specific attributes and specificities, should be pursued. PMID- 26827252 TI - Hansen's disease: Descriptions of novel ultrasonographic findings. PMID- 26827249 TI - [Drug abuse in nursing students]. AB - OBJECTIVE: To determine the patterns of substance abuse of students attending the Lugo School of Nursing. METHOD: Observational, descriptive and cross-sectional study in the classroom carried out by survey research in April 2015. RESULTS: 61.5% of students participated (185), 83.2% of whom were females. The first addictive substance consumed by participants was tobacco (at 15 years old). In the last month cigarettes were consumed by 36.2% of students, while alcohol was consumed by 89.9% (58.4% of the total got drunk). 2.2% were consuming tranquilizers/hypnotics in the same time period. The most widely used illegal drug was cannabis (17.8%) and then cocaine (2.2%). There is a significant correlation between illegal drug consumption and being male, smoking cigarettes or drinking alcohol, living alone or with friends (not family), have poor academic performance and public drinking (botellon). There were no association between illegal drugs and sports or reading. Polydrug use was also studied: a 16.2% declared to have consumed alcohol and cannabis simultaneously, and a 4.9% alcohol and cocaine. CONCLUSIONS: Consumption patterns are similar compared to the general population in that age group, with some of them being higher. Therefore, it is necessary to take measures in order to prevent substance abuse at the university level. PMID- 26827248 TI - Food allergies can persist after myeloablative hematopoietic stem cell transplantation in dedicator of cytokinesis 8-deficient patients. PMID- 26827253 TI - Sexual Anatomy and Function in Women With and Without Genital Mutilation: A Cross Sectional Study. AB - INTRODUCTION: Female genital mutilation (FGM), the partial or total removal of the external genitalia for non-medical reasons, can affect female sexuality. However, only few studies are available, and these have significant methodologic limitations. AIM: To understand the impact of FGM on the anatomy of the clitoris and bulbs using magnetic resonance imaging and on sexuality using psychometric instruments and to study whether differences in anatomy after FGM correlate with differences in sexual function, desire, and body image. METHODS: A cross sectional study on sexual function and sexual anatomy was performed in women with and without FGM. Fifteen women with FGM involving cutting of the clitoris and 15 uncut women as a control group matched by age and parity were prospectively recruited. Participants underwent pelvic magnetic resonance imaging with vaginal opacification by ultrasound gel and completed validated questionnaires on desire (Sexual Desire Inventory), body image (Questionnaire d'Image Corporelle [Body Image Satisfaction Scale]), and sexual function (Female Sexual Function Index). MAIN OUTCOME MEASURES: Primary outcomes were clitoral and bulbar measurements on magnetic resonance images. Secondary outcomes were sexual function, desire, and body image scores. RESULTS: Women with FGM did not have significantly decreased clitoral glans width and body length but did have significantly smaller volume of the clitoris plus bulbs. They scored significantly lower on sexual function and desire than women without FGM. They did not score lower on Female Sexual Function Index sub-scores for orgasm, desire, and satisfaction and on the Questionnaire d'Image Corporelle but did report significantly more dyspareunia. A larger total volume of clitoris and bulbs did not correlate with higher Female Sexual Function Index and Sexual Desire Inventory scores in women with FGM compared with uncut women who had larger total volume that correlated with higher scores. CONCLUSION: Women with FGM have sexual erectile tissues for sexual arousal, orgasm, and pleasure. Women with sexual dysfunction should be appropriately counseled and treated. PMID- 26827255 TI - Polymer functionalized nanocomposites for metals removal from water and wastewater: An overview. AB - Pollution by metal and metalloid ions is one of the most widespread environmental concerns. They are non-biodegradable, and, generally, present high water solubility facilitating their environmental mobilisation interacting with abiotic and biotic components such as adsorption onto natural colloids or even accumulation by living organisms, thus, threatening human health and ecosystems. Therefore, there is a high demand for effective removal treatments of heavy metals, making the application of adsorption materials such as polymer functionalized nanocomposites (PFNCs), increasingly attractive. PFNCs retain the inherent remarkable surface properties of nanoparticles, while the polymeric support materials provide high stability and processability. These nanoparticle matrix materials are of great interest for metals and metalloids removal thanks to the functional groups of the polymeric matrixes that provide specific bindings to target pollutants. This review discusses PFNCs synthesis, characterization and performance in adsorption processes as well as the potential environmental risks and perspectives. PMID- 26827256 TI - Electrochemical sulfide removal and caustic recovery from spent caustic streams. AB - Spent caustic streams (SCS) are produced during alkaline scrubbing of sulfide containing sour gases. Conventional methods mainly involve considerable chemical dosing or energy expenditures entailing high cost but limited benefits. Here we propose an electrochemical treatment approach involving anodic sulfide oxidation preferentially to sulfur coupled to cathodic caustic recovery using a two compartment electrochemical system. Batch experiments showed sulfide removal efficiencies of 84 +/- 4% with concomitant 57 +/- 4% efficient caustic production in the catholyte at a final concentration of 6.4 +/- 0.1 wt% NaOH (1.6 M) at an applied current density of 100 A m(-2). Subsequent long-term continuous experiments showed that stable cell voltages (i.e. 2.7 +/- 0.1 V) as well as constant sulfide removal efficiencies of 67 +/- 5% at a loading rate of 47 g(S) L(-1) h(-1) were achieved over a period of 77 days. Caustic was produced at industrially relevant strengths for scrubbing (i.e. 5.1 +/- 0.9 wt% NaOH) at current efficiencies of 96 +/- 2%. Current density between 0 and 200 A m(-2) and sulfide loading rates of 50-200 g(S) L(-1) d(-1) were tested. The higher the current density the more oxidized the sulfur species produced and the higher the sulfide oxidation. On the contrary, high loading rate resulted in a reduction of sulfide oxidation efficiency. The results obtained in this study together with engineering calculations show that the proposed process could represent a cost effective approach for sodium and sulfur recovery from SCS. PMID- 26827250 TI - Effectiveness of an online insomnia program (SHUTi) for prevention of depressive episodes (the GoodNight Study): a randomised controlled trial. AB - BACKGROUND: In view of the high co-occurrence of depression and insomnia, a novel way to reduce the risk of escalating depression might be to offer an insomnia intervention. We aimed to assess whether an online self-help insomnia program could reduce depression symptoms. METHODS: We did this randomised controlled trial at the Australian National University in Canberra, Australia. Internet users (aged 18-64 years) with insomnia and depression symptoms, but who did not meet criteria for major depressive disorder, were randomly assigned (1:1), via computer-generated randomisation, to receive SHUTi, a 6 week, modular, online insomnia program based on cognitive behavioural therapy for insomnia, or HealthWatch, an interactive, attention-matched, internet-based placebo control program. Randomisation was stratified by age and sex. Telephone-based interviewers, statisticians, and chief investigators were masked to group allocation. The primary outcome was depression symptoms at 6 months, as measured with the Patient Health Questionnaire (PHQ-9). The primary analysis was by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000121965. FINDINGS: Between April 30, 2013, and June 9, 2014, we randomly assigned 1149 participants to receive SHUTi (n=574) or HealthWatch (n=575), of whom 581 (51%) participants completed the study program assessments at 6 weeks and 504 (44%) participants completed 6 months' follow-up. SHUTi significantly lowered depression symptoms on the PHQ-9 at 6 weeks and 6 months compared with HealthWatch (F[degrees of freedom 2,640.1]=37.2, p<0.0001). Major depressive disorder was diagnosed in 22 (4%) participants at 6 months (n=9 in the SHUTi group and n=13 in the HealthWatch group), with no superior effect of SHUTi versus HealthWatch (Fisher's exact test=0.52; p=0.32). No adverse events were reported. INTERPRETATION: Online cognitive behaviour therapy for insomnia treatment is a practical and effective way to reduce depression symptoms and could be capable of reducing depression at the population level by use of a fully automatised system with the potential for wide dissemination. FUNDING: Australian National Health and Medical Research Council. PMID- 26827254 TI - Melphalan-flufenamide is cytotoxic and potentiates treatment with chemotherapy and the Src inhibitor dasatinib in urothelial carcinoma. AB - BACKGROUND: Chemotherapy options in advanced urothelial carcinoma (UC) remain limited. Here we evaluated the peptide-based alkylating agent melphalan flufenamide (mel-flufen) for UC. METHODS: UC cell lines J82, RT4, TCCsup and 5637 were treated with mel-flufen, alone or combined with cisplatin, gemcitabine, dasatinib or bestatin. Cell viability (MTT assay), intracellular drug accumulation (liquid chromatography) apoptosis induction (apoptotic cell nuclei morphology, western blot analysis of PARP-1/caspase-9 cleavage and Bak/Bax activation) were evaluated. Kinome alterations were characterized by PathScan array and phospho-Src validated by western blotting. Aminopeptidase N (ANPEP) expression was evaluated in UC clinical specimens in relation to patient outcome. RESULTS: In J82, RT4, TCCsup and 5637 UC cells, mel-flufen amplified the intracellular loading of melphalan in part via aminopeptidase N (ANPEP), resulting in increased cytotoxicity compared to melphalan alone. Mel-flufen induced apoptosis seen as activation of Bak/Bax, cleavage of caspase-9/PARP-1 and induction of apoptotic cell nuclei morphology. Combining mel-flufen with cisplatin or gemcitabine in J82 cells resulted in additive cytotoxic effects and for gemcitabine also increased apoptosis induction. Profiling of mel-flufen induced kinome alterations in J82 cells revealed that mel-flufen alone did not inhibit Src phosphorylation. Accordingly, the Src inhibitor dasatinib sensitized for mel-flufen cytotoxicity. Immunohistochemical analysis of the putative mel flufen biomarker ANPEP demonstrated prominent expression levels in tumours from 82 of 83 cystectomy patients. Significantly longer median overall survival was found in patients with high ANPEP expression (P = 0.02). CONCLUSION: Mel-flufen alone or in combination with cisplatin, gemcitabine or Src inhibition holds promise as a novel treatment for UC. PMID- 26827258 TI - Diving Into Cabazitaxel's Mode of Action: More Than a Taxane for the Treatment of Castration-Resistant Prostate Cancer Patients. AB - Prostate cancer is a molecularly heterogeneous disease, and mechanisms of action of taxanes and potential mechanisms of resistance are not clearly defined. Taxanes are microtubule-stabilizing agents resulting in the slowing or blocking of mitosis at the metaphase-anaphase transition and induction of apoptotic cell death. Taxanes also can inhibit androgen receptor pathway. To date, several factors have been associated with taxane resistance, including alterations in tubulin, the effect of drug efflux pumps, and the dysfunctional regulation of signaling pathways that may be involved in resistance to therapy. Preclinical and clinical data support the distinct activity of cabazitaxel in prostate cancer that may overcome resistance to prior taxanes or hormonal therapies. It is challenging to define the most adequate therapeutic sequence for each patient. Moreover, the identification of molecular markers of resistance may help to select patients for specific therapies. PMID- 26827257 TI - Low Pretreatment Impulsivity and High Medication Adherence Increase the Odds of Abstinence in a Trial of N-Acetylcysteine in Adolescents with Cannabis Use Disorder. AB - BACKGROUND: In light of recent progress toward pharmacologic interventions to treat adolescent cannabis use disorder, it is important to consider which adolescent characteristics may be associated with a favorable response to treatment. This study presents secondary analyses from a parent randomized controlled trial of N-acetylcysteine (NAC) in adolescents with cannabis use disorder. We hypothesized that high pretreatment impulsivity and medication non adherence would be associated with reduced abstinence rates. METHODS: Participants were treatment-seeking adolescents (N=115) who met criteria for cannabis use disorder and were assessed for pretreatment impulsivity. They received 1200 mg NAC or placebo orally twice daily for 8 weeks. An intent-to treat analysis using a repeated-measures logistic regression model was used to relate pretreatment impulsivity (Barratt Impulsiveness Scale) and treatment group to abstinence rates, measured by urine cannabinoid tests. To explore mechanisms by which NAC may reduce cannabis use, relationships between impulsivity, adherence, and abstinence were assessed in a second statistical model using data from participants with recorded adherence and urine cannabinoid test results (n=54). RESULTS: In the intent-to-treat analysis, low pretreatment impulsivity, NAC treatment, and negative baseline urine cannabinoid test results independently increased the odds of having negative urine cannabinoid tests during treatment (OR=2.1, 2.3, and 5.3 respectively). In the sample of participants with adherence data (n=54), adherence tripled the odds of abstinence. Notably, the effect of adherence on abstinence was only observed in the NAC treatment group. Lastly, although the highly impulsive participants had reduced rates of abstinence, highly impulsive individuals adherent to NAC treatment had increased abstinence rates compared to non-adherent individuals. CONCLUSION: Low impulsivity, NAC treatment, medication adherence, and baseline negative cannabinoid testing were associated with increased rates of abstinence in adolescents seeking treatment for cannabis use disorder. Efforts to optimize pharmacotherapy adherence may be particularly crucial for highly impulsive individuals. Understanding and addressing factors, such as impulsivity and adherence, which may affect outcomes, may aid in the successful evaluation and development of potentially promising pharmacotherapies. PMID- 26827259 TI - Chemical and Plant-Based Insect Repellents: Efficacy, Safety, and Toxicity. AB - Most emerging infectious diseases today are arthropod-borne and cannot be prevented by vaccinations. Because insect repellents offer important topical barriers of personal protection from arthropod-borne infectious diseases, the main objectives of this article were to describe the growing threats to public health from emerging arthropod-borne infectious diseases, to define the differences between insect repellents and insecticides, and to compare the efficacies and toxicities of chemical and plant-derived insect repellents. Internet search engines were queried with key words to identify scientific articles on the efficacy, safety, and toxicity of chemical and plant-derived topical insect repellants and insecticides to meet these objectives. Data sources reviewed included case reports; case series; observational, longitudinal, and surveillance studies; and entomological and toxicological studies. Descriptive analysis of the data sources identified the most effective application of insect repellents as a combination of topical chemical repellents, either N-diethyl-3 methylbenzamide (formerly N, N-diethyl-m-toluamide, or DEET) or picaridin, and permethrin-impregnated or other pyrethroid-impregnated clothing over topically treated skin. The insecticide-treated clothing would provide contact-level insecticidal effects and provide better, longer lasting protection against malaria-transmitting mosquitoes and ticks than topical DEET or picaridin alone. In special cases, where environmental exposures to disease-transmitting ticks, biting midges, sandflies, or blackflies are anticipated, topical insect repellents containing IR3535, picaridin, or oil of lemon eucalyptus (p-menthane 3, 8-diol or PMD) would offer better topical protection than topical DEET alone. PMID- 26827260 TI - Efficacy of Topical Treatments for Chrysaora chinensis Species: A Human Model in Comparison with an In Vitro Model. AB - OBJECTIVES: This study sought to create a model for testing topical treatment of jellyfish stings. It sought to determine which treatments 1) stimulate/inhibit nematocyst discharge; 2) decrease pain; and 3) decrease skin inflammation; it also sought to discover whether there is a clinical correlation between stimulated nematocyst discharge observed in vitro to the pain and erythema experienced by humans stung by a particular species of jellyfish, C chinensis. METHODS: Chrysaora chinensis stung 96 human subjects, who were then treated with isopropyl alcohol, hot water, acetic acid, papain meat tenderizer, lidocaine, or sodium bicarbonate. Pain and erythema were measured. In a separate experiment, nematocysts were examined microscopically after exposure to the same topical treatments used in the human experiment. RESULTS: Forearms treated with papain showed decreased mean pain over the first 30 minutes after being stung, relative to placebo, although only by a small amount. The other topical treatments tested did not reach statistical significance. Sodium bicarbonate may reduce erythema after 30 minutes of treatment; sodium bicarbonate and papain may reduce erythema at 60 minutes. The other topical treatments tested did not reach statistical significance. Nematocyst discharge in vitro occurred when tentacles of C chinensis were exposed to acetic acid or isopropyl alcohol. Sodium bicarbonate, papain, heated water, and lidocaine did not induce nematocyst discharge. CONCLUSIONS: Papain-containing meat tenderizer used as a topical treatment for C chinensis stings may decrease pain. Although there is published experimental support for the concept that in vitro nematocyst discharge correlates with in vivo human pain perception, no definitive randomized controlled trial, including ours, has yet provided incontrovertible evidence of this assertion. Despite this study's limitations, it presents a viable basis for future human studies looking at the efficacy of topical treatments for jellyfish stings. PMID- 26827261 TI - The aftermath of a bushfire. PMID- 26827262 TI - Ice Climbing Festival in Sochi 2014 Winter Olympics: Medical Management and Injury Analysis. AB - OBJECTIVE: Sports ice climbing (SIC) is developing rapidly as an independent sport with Olympic potentials. To date there has been no prior systematic evaluation of injury risks and injury patterns in a SIC-specific setting. METHODS: This paper reports injury statistics collected during the Ice Climbing Festival, which was held during the XXII Winter Olympics in Sochi, Russia. More than 2500 amateur climbers and 53 professional athletes climbed during 16 days on a dry tooling lead-difficulty, and a 17-m vertical ice wall (grade M4/M5 or Union Internationale des Associations d'Alpinisme [UIAA] V+/VI-). RESULTS: The injury incidence rates were 0.82/100 in lead-difficulty and 0.83/100 in speed ice climbing with an overall incidence rate of 0.83/100. The injury risk in amateur climbers was 248 injuries per 1000 hours of sports activities. There were no major accidents or fatalities during the event. SIC could be graded I according to UIAA Fatality Risk Classification. Penetrating and superficial soft tissue injuries (cuts and bruises) were the most common. The anteromedial aspects of the thigh and knee were the most typical injury locations. CONCLUSIONS: The findings from this study provide an opportunity to compare injury patterns in SIC with what has previously been reported for traditional ice climbing. SIC has lower fatality risks, higher minor injury rates, and comparable injury severity to traditional ice climbing. The main limitation of our findings is that they were obtained on a population of amateur ice climbers with no previous experience. Further research should be performed to define injury risks in professional competitive ice climbers, and standard methodologies for reporting injuries should be considered. PMID- 26827263 TI - Early infant diagnosis and post-exposure prophylaxis for HIV- exposed infants. AB - Recent scientific evidence suggests that early initiation of antiretroviral therapy (ART) among infants exposed perinatally to HIV has beneficial effects on their health and survival, and may even induce remission. This has led to the roll-out of early infant diagnosis (EID) of HIV and early treatment. Also, there is talk of using ART as post-exposure prophylaxis (PEP) to prevent mother-to child transmission. EID involves carrying out diagnostic tests before initiating ART. In India, current programme design of centralised diagnosis has been resulting in poor access to diagnosis and treatment. To save the lives of HIV infected infants, it is important to prevent delay. Another issue to be kept in mind is that the results of HIV tests may turn negative after the initiation of ART. This could be due to viral remission induced by ART or false positive initial results. Differentiating between the two is difficult. To deal with such cases, we need to develop a clinical algorithm and tools for capacity-building in counselling. The use of ART as PEP is expected to encounter further challenges. Between ART as PEP and EID, the later has advantages from an ethical perspective. There is a need to address the ethical issues within the EID programme by strengthening the current mechanisms for protecting the rights of HIV-exposed infants. PMID- 26827264 TI - Increased serum CXCR2 ligand levels in livedo vasculopathy with winter ulcerations: Possible contribution of neutrophil recruitment to lesional skin. PMID- 26827265 TI - The effectiveness of small changes for pressure redistribution; using the air mattress for small changes. AB - Observing small changes (SCs) at specific sites is a new form of managing changes in position. We investigated SCs at specific sites considering interface pressure, contact area, body alignment and physical sensation in nine healthy female adults and evaluated SCs using the air mattress that was divided into six cells (A-F). Thirty-three SC combinations at one or several sites were evaluated. Pressure in the sacral region significantly decreased in 28 SC combinations compared with the supine position (p < 0.05), and the effect of pressure redistribution was greater when SCs were applied at several instead of a single site. The contact area at 17 of the 28 SC combinations significantly increased (p < 0.05). Among sites ranked based on interface pressure, body alignment and physical sensation, SCs at sites BCE, AE and BD were the most favorable. The common feature among these three combinations was that they involved tilting the buttock region and one other site. The findings suggested that SCs at the buttock region could reduce disruptions in alignment as well as the impact on physical sensation caused by the body sinking into the mattress and improve interface pressure redistribution via increased contact area with the mattress. PMID- 26827266 TI - Long-term safety and seizure outcome in Japanese patients with Lennox-Gastaut syndrome receiving adjunctive rufinamide therapy: An open-label study following a randomized clinical trial. AB - PURPOSE: To evaluate the long-term safety and seizure outcome in Japanese patients with Lennox-Gastaut syndrome (LGS) receiving adjunctive rufinamide therapy. SUBJECTS AND METHODS: We conducted an open-label extension study following a 12-week multicenter, randomized, double-blind, placebo-controlled study of adjunctive rufinamide therapy in Japanese patients with LGS. Fifty-four patients participated in the extension study. Seizure frequency was evaluated until 52 weeks after the start of the extension study. Adverse events (AEs) were evaluated throughout both studies. KEY FINDINGS: Of the 54 patients, 41 (75.9%) completed the extension study. The median duration of exposure to rufinamide was 818.0 days in all 54 patients, and 38 patients (70.4%) received rufinamide for 2 years or more. The median percent change in the frequency of tonic-atonic seizures relative to the frequency at the start of the double-blind study was 39.3% (12 weeks), -40.6% (24 weeks), -46.8% (32 weeks), -47.6% (40 weeks), and 36.1% (52 weeks). Reduction of total seizure frequency was also maintained until 52 weeks. Frequent treatment-related AEs were somnolence (20.4%), decreased appetite (16.7%), transient seizure aggravation including status epilepticus (13.0%), vomiting (11.1%), and constipation (11.1%). Adverse events were mild or moderate, except for transient seizure aggravation in three patients. Adverse events resulting in discontinuation of rufinamide were decreased appetite, drug eruption, and worsening of underlying autism. When clinically notable weight loss was defined as a decrease >= 7% relative to baseline, 22 patients (40.7%) experienced weight loss at least once during long-term observation, although weight loss was reported as an AE in only three patients. SIGNIFICANCE: This study demonstrated a long-term benefit of rufinamide as adjunctive therapy for Japanese patients with LGS. Exacerbation of seizures and decreased appetite/weight loss should be monitored carefully. PMID- 26827267 TI - International Trends in Adolescent Screen-Time Behaviors From 2002 to 2010. AB - PURPOSE: Engaging in prolonged screen-time behaviors (STBs) is detrimental for health. The objective of the present analyses was to examine temporal trends in TV viewing and computer use among adolescents across 30 countries. METHODS: Data were derived from the cross-national Health Behaviour in School-aged Children study. Data on TV viewing and computer use for gaming and nongaming purposes were collected in 2002 (n = 139,725 [51.4% girls]), 2006 (n = 149,251 [51.3% girls]), and 2010 (n = 154,845 [51.2% girls]). The temporal trends in TV viewing and computer use were each tested for all countries combined and for each individual country by sex-specific univariate analysis of variance. RESULTS: Between 2002 and 2010, TV viewing decreased slightly in most of the 30 countries among both boys and girls. This decrease was more than offset by a sharp increase in computer use, which was consistent across all countries. Overall, boys reported more hours of STBs. They also reported a slightly larger decrease in TV viewing and slightly larger increase in computer use. STBs were generally more frequent on weekend days. CONCLUSIONS: The overall cross-national increases in STBs should be a call to action for public health practitioners, policy-makers, and researchers that interventions specifically focused on reducing STBs in youth are sorely needed. Because all countries experienced a trend in the same direction, it might be fruitful to learn more about the determinants of STBs among those countries in which hours of STBs are generally low as compared with other countries. PMID- 26827268 TI - Waterborne citalopram has anxiolytic effects and increases locomotor activity in the three-spine stickleback (Gasterosteus aculeatus). AB - Citalopram is an antidepressant drug, which acts by inhibiting the re-uptake of serotonin from the synaptic cleft into the pre-synaptic nerve ending. It is one of the most common drugs used in treatment of depression, it is highly lipophilic and frequently found in sewage treatment plant effluents and surface waters around the world. Citalopram and other selective serotonin re-uptake inhibitors have, at concentrations that occur in nature, been shown to have behavioural as well as physiological effects on fish and other animals. This study is the result of several different experiments, intended to analyse different aspects of behavioural effects of chronic citalopram exposure in fish. Our model species the three-spine stickleback is common in the entire northern hemisphere and is considered to be a good environmental sentinel species. Female three-spine sticklebacks were exposed to 0, 1.5 and 15MUg/l nominal concentrations of citalopram for 21 days and subjected to the novel tank (NT) diving test. In the NT test, the fish exposed to 1.5MUg/l, but not the 15MUg/l fish made a significantly higher number of transitions to the upper half and stayed there for significantly longer time than the fish exposed to 0MUg/l. The 15MUg/l group, however, displayed a significantly lower number of freeze bouts and a shorter total freezing time. The test for locomotor activity included in the NT test showed that fish treated with 1.5 and 15MUg/l displayed a significantly higher swimming activity than control fish both 5-7 and 15-17min after the start of the experiment. In the next experiment we compared fish exposed to 1.5MUg/l and 0.15MUg/l to pure water controls with regard to shoaling intensity and found no effect of treatment. In the final experiment the propensity of fish treated with 1.5MUg/l to approach an unknown object and aggressive behaviour was investigated using the Novel Object test and a mirror test, respectively. The exposed fish ventured close to the unknown object significantly more often and stayed there for significantly longer time than unexposed fish. The aggression test yielded no statistically significant effects. It is concluded that citalopram changes the behaviour of the three-spine stickleback in a way that is likely to have ecological consequences and that it must not be considered an environmentally safe pharmaceutical. PMID- 26827269 TI - Is salivary gland ultrasonography a useful tool in Sjogren's syndrome? PMID- 26827270 TI - [Physical activity and cancer: Update and literature review]. AB - Physical activity is a key determinant of public health and contributes to decreasing the prevalence of many diseases. Cancer is the leading cause of death worldwide. Physical activity, accessible to the entire population, could prevent up to 25% of cancers, in addition to improving survival rates and quality of life in cancer patients. Physical activity acts via various mechanisms to slow or decrease tumor growth, including the production and bioavailability of sex hormones, insulin resistance and insulin secretion, and inflammation. In primary prevention, physical activity reduces breast cancer risk by 15-20% and colorectal cancer risk by 24%. All-cause mortality is reduced by 33% in cancer survivors who exercise. Health-related quality of life, fatigue and depression are enhanced by the practice of physical activity in cancer patients. In the general population, the global recommendations on physical activity for health, published by the World Health Organisation, are suggested as a means of primary prevention of cancer. In cancer patients, an adapted physical activity routine is promoted from the very beginning of patient care to decrease fatigue as well as improve tolerance and benefits of treatments. PMID- 26827271 TI - [Aortitis]. PMID- 26827272 TI - [Computerized ranking test in three French universities: Staff experience and students' feedback]. AB - BACKGROUND: The year 2016 will be pivotal for the evaluation of French medical students with the introduction of the first computerized National Ranking Test (ECNi). The SIDES, online electronic system for medical student evaluation, was created for this purpose. All the universities have already organized faculty exams but few a joint computerized ranking test at several universities simultaneously. We report our experience on the organization of a mock ECNi by universities Paris Descartes, Paris Diderot and Paris 13. METHODS: Docimological, administrative and technical working groups were created to organize this ECNi. Students in their fifth year of medical studies, who will be the first students to sit for the official ECNi in 2016, were invited to attend this mock exam that represented more than 50% of what will be proposed in 2016. A final electronic questionnaire allowed a docimological and organizational evaluation by students. An analysis of ratings and rankings and their distribution on a 1000-point scale were performed. RESULTS: Sixty-four percent of enrolled students (i.e., 654) attended the three half-day exams. No difference in total score and ranking between the three universities was observed. Students' feedback was extremely positive. Normalized over 1000 points, 99% of students were scored on 300 points only. Progressive clinical cases were the most discriminating test. CONCLUSION: The organization of a mock ECNi involving multiple universities was a docimological and technical success but required an important administrative, technical and teaching investment. PMID- 26827273 TI - [Takayasu arteritis]. AB - Takayasu arteritis is a chronic inflammatory vasculitis of unknown origin affecting large vessels, predominantly the aorta and its main branches. Vessel inflammation leads to wall thickening, fibrosis, and stenosis. The lesions are often asymptomatic leading to limb numbness, transient ischemic attack, cardiovascular event and renovascular hypertension. Treatment is based on corticosteroids, immunosuppressant and biologics if necessary. Endovascular treatment and open-surgery can be useful for end-organ ischemia relief. PMID- 26827274 TI - [Inherited primitive and secondary polycythemia]. AB - Myeloproliferative disorders and secondary polycythemia cover most of the polycythemia cases encountered in daily practice. Inherited polycythemias are rare entities that have to be suspected when the classical causes of acquired polycythemia have been ruled out. Recent advances were made in the understanding of these pathologies, which are still little known to the physicians. This review reports the state of knowledge and proposes an algorithm to follow when confronted to a possible case of inherited polycythemia. PMID- 26827275 TI - Does rapid maxillary expansion affect nasopharyngeal airway? A prospective Cone Beam Computerised Tomography (CBCT) based study. AB - BACKGROUND AND PURPOSE: There is limited literature discussing the three dimnesional (3D) impact of rapid maxillary expansion (RME) on upper airway. The purpose of this prospective Cone Beam Computerised Tomography (CBCT) based study is to assess the immediate 3D effects and to correlate the volumteric changes in the upper naspharyngeal airway spaces secondary to RME. MATERIALS AND METHODS: Seventeen participants (8 male, 9 female, with a mean age of 12.6 +/- 1.8 years), who required RME for the management of narrow maxillary arch, were recruited for this study. The prescribed expansion regimen was quarter turn (0.25 mm), twice a day until over-expansion was achieved. The mean period for the active phase was 14 days with a range of 12-21 days. Pretreatment (T1) and immediate post expansion (T2) CBCT images were obtained and then processed using ITK snap and OnDemand3D softwar packages. Paired t-test and Interclass Correlation Coefficient (ICC) were used to assess the reproducibility of the measurements, student t-test (P < 0.05) and Pearson Correlation Coefficient (PCC) were applied to evaluate the volumetric changes in the nasopharyngeal airway spaces, linear dentolaveolar changes and correlate these changes. MAIN FINDINGS: Though, the data of one patient was excluded from the study, owing to major differences (>5 degrees) in the head and neck posture between T1 and T2 CBCT scans, the study' findings shows that bonded RME is an effective dentoalveolar expander in growing patients (P= 0.01) with an average expansion of 3.7 mm and 2.8 mm in males and females respectively. Likewise, the upper nasopharynx (UNP) expanded significantly (15.2% in males and 12% in females). In comparison, the upper retropalatal space (URP) was significantly reduced, by almost one sixth of its original volume, more in males than females, 11.2% and 2.8% respectively. A strong direct correlation between the maxillary sinus volumetric changes, and between appliance expansion and dentoalveolar expansion were evident (PCC = 0.86, 0.75, respectively). There was also a moderate correlation between changes in the UNP and URP spaces. CONCLUSIONS: RME was found to be an effective dentoalveolar expander and significantly augment the UNP and minimize the URP space. A similar comparative clinical study with long-term follow-up would be beneficial in accurately deteremining the clinical impact of RME on the airway and breathing as well as the stability of these effects. PMID- 26827276 TI - Significance of metabolite extraction method for evaluating sulfamethazine toxicity in adult zebrafish using metabolomics. AB - Recently, environmental metabolomics has been introduced as a next generation environmental toxicity method which helps in evaluating toxicity of bioactive compounds to non-target organisms. In general, efficient metabolite extraction from target cells is one of the keys to success to better understand the effects of toxic substances to organisms. In this regard, the aim of this study is (1) to compare two sample extraction methods in terms of abundance and quality of metabolites and (2) investigate how this could lead to difference in data interpretation using pathway analysis. For this purpose, the antibiotic sulfamethazine and zebrafish (Danio rerio) were selected as model toxic substance and target organism, respectively. The zebrafish was exposed to four different sulfamethazine concentrations (0, 10, 30, and 50mg/L) for 72h. Metabolites were extracted using two different methods (Bligh and Dyer and solid-phase extraction). A total of 13,538 and 12,469 features were detected using quadrupole time-of-flight liquid chromatography mass spectrometry (QTOF LC-MS). Of these metabolites, 4278 (Bligh and Dyer) and 332 (solid phase extraction) were found to be significant after false discovery rate adjustment at a significance threshold of 0.01. Metlin and KEGG pathway analysis showed comprehensive information from fish samples extracted using Bligh and Dyer compared to solid phase extraction. This study shows that proper selection of sample extraction method is critically important for interpreting and analyzing the toxicity data of organisms when metabolomics is applied. PMID- 26827277 TI - Linking mobile source-PAHs and biological effects in traffic police officers and drivers in Rawalpindi (Pakistan). AB - The aim of this study was to evaluate the effect of traffic related polycyclic aromatic hydrocarbons (PAHs) on blood parameters of subjects, including traffic police officers (TP), drivers (DR) and control subjects (CN) with presumably different levels of exposure. We quantified the urinary 1-hydroxypyrene (1 OHPyr), alpha-naphthol and beta-naphthol (alpha- and beta-naph) as biomarkers of exposure to PAHs in relation with biomarkers of effect (Hb, MCV, PCV, PLT, RBCs), biomarkers of inflammation/infection (CRP, WBCs), oxidative stress (SOD) and oxidative DNA damage i.e. 8-hydroxy-2-deoxyguanosine (8-OHdG). Results showed that mean 1-OHPyr, alpha-naph and beta-naph concentrations were significantly higher in TPs (0.98, 1.55, and 1.9umolmol-Cr(-1), respectively, p<0.05) than CNs (0.7, 0.6; 0.67umolmol-Cr(-1), respectively, P<0.05). Furthermore, WBC and CRP were found in higher concentrations in TPs than CNs (7.04*10(3)uL(-1) and 0.95mgL(-1) vs. 5.1*10(3)uL(-1) and 0.54mgL(-1), respectively). The urinary 8 OHdG level, a biomarker of oxidative DNA damage, was higher in TPs than both CN and DR subjects (48ngmg-Cr(-1), 24ngmg-Cr(-1) and 33ngmg-Cr(-1), respectively). Self-reported health assessment indicates that, on the basis of daily time spent in the middle of heavy traffic, TPs and DRs more frequently suffered from adverse head and respiratory symptoms. The PCA analysis evidenced the impact of traffic pollution on exposure biomarkers and DNA damage. The study suggests that traffic pollution may be associated with important health risk, in particular on the respiratory system, not only for workers exposed to traffic exhausts but also for general public. Finally, vehicular air pollution in the city of Rawalpindi should be a high-priority concern for the Pakistan Government that needs to be addressed. PMID- 26827278 TI - Purification of influenza deoxyribonucleic acid-based vaccine using agmatine monolith. AB - Lately, researchers have made several efforts to improve vaccine production to fight highly contagious respiratory diseases like influenza. One of the most promising options for reducing the impact of this virus is DNA vaccination. However, a large quantity of highly pure plasmid DNA (pDNA) is necessary to attain this goal. The present work describes the production and purification of the plasmid NTC7482-41H-VA2HA expressing influenza virus hemagglutinin using an agmatine monolith. This ligand was chosen to purify supercoiled (sc) pDNA from complex lysates because of its versatile multimodal character. Its natural intervention in several biological systems together with its similarity with the highly studied arginine ligand allowed the development of a simpler and more specific purification process. Agmatine works under two strategies: descending ammonium sulfate gradient and ascending sodium chloride gradient. Furthermore, pH manipulation revealed an important role in pDNA isoforms selectivity. Dynamic binding capacity (DBC) experiments were performed varying different parameters and showed an increase with pDNA concentration, while high flow rate and high pH had the opposite effect. Sc pDNA was purified with high yield and was efficient with respect to cell transfection and cell viability. This monolith showed to be appropriate to purify the plasmid NTC7482-41H-VA2HA, providing a valuable tool for pDNA influenza vaccines preparation. PMID- 26827279 TI - UFLC-Q-TOF/MS based screening and identification of the metabolites in plasma, bile, urine and feces of normal and blood stasis rats after oral administration of hydroxysafflor yellow A. AB - The dried flower of Carthamus tinctorius L. (honghua) is a widely used traditional Chinese medicine in clinics to treat coronary heart disease, hypertension, and cerebrovascular disease due to its functions of ameliorating circulation and removing blood stasis. Hydroxysafflor yellow A (HSYA) is an active marker component of honghua. In this paper, ultra-flow liquid chromatography coupled with quadrupole-time-of-flight mass-spectrometry (UFLC-Q TOF/MS) was established and successfully applied to the detection and identification of the metabolites in bile, urine, plasma and feces samples of normal and model rats with orally administrated HSYA. A total of 8 metabolites were observed in normal rats, while 7 metabolites were detected in model rats. The distribution of metabolites in the plasma, bile, urine and feces of normal and model rats had obvious differences. The major in vivo metabolic pathways for HSYA included hydroxylation, hydroxylation+methylation, acetylation and glucuronidation, and there were also dehydration, hydrogenation, hydration, and hydroxylation+glucuronidation. All of these metabolites were reported for the first time, and these results are valuable and important for the understanding of the metabolic process and therapeutic mechanism of HSYA and some other pigments in honghua. PMID- 26827280 TI - Trace analysis of sulforaphane in bee pollen and royal jelly by liquid chromatography-tandem mass spectrometry. AB - In this study, we investigate for the first time the presence of sulforaphane (SFN) residues in two of the most currently consumed food/dietary supplements, royal jelly and bee pollen. Chromatography-tandem mass spectrometry (LC-MS/MS) was the method employed, the mass spectrometer consisting of an ion-trap mass analyzer used with electrospray ionization (ESI) in positive ion mode. An efficient sample treatment involving a solvent extraction with methanol, centrifugation, and concentration in a rotary evaporator was proposed. In all cases average analyte recoveries were between 92 and 106%. Chromatographic analysis (16min) was performed on a core-shell technology based column (Kinetex C18, 150*4.6mm, 2.6MUm, 100A). The mobile phase consisted of 0.02M ammonium formate in water and acetonitrile, with a flow rate of 0.5mL/min in gradient elution mode. The fully validated method was selective, linear from 8 to 1000MUg/kg (bee pollen), or from 10 to 1250MUg/kg (royal jelly), precise and accurate; relative standard deviation (% RSD) and relative error (% RE) values were below 10%. Low limits of detection (LOD) and quantification (LOQ) were obtained, namely, 3MUg/kg (LOD) and 8 (bee pollen) and 10 (royal jelly) MUg/kg (LOQ). The method was applied for SFN analysis in several royal jelly and bee pollen samples. SFN was detected at trace levels in some bee pollen samples (<23MUg/kg) examined, whilst SFN went undetected in the royal jelly samples analyzed. PMID- 26827281 TI - Extraction and purification of IgG by hydrophilic organic solvent salting-out extraction. AB - The distribution of IgG in different salting-out extraction systems (SOESs), including ethanol/K2HPO4, Na2CO3, and trisodium citrate, was investigated. The SOESs that were composed of 20% K2HPO4 (w/w)-14% ethanol (w/w), 19% Na2CO3 (w/w) 13% ethanol (w/w) and 25% trisodium citrate (w/w)-19% ethanol (w/w) showed satisfactory results, with IgG recovery rates as high as 97.4%, 93.1%, and 90.2%, respectively. ELISA, CD and IR analyses confirmed the active retention and structural constant of IgG in the K2HPO4-ethanol system. An optimized system that consisted of 14% ethanol (w/w)-20% K2HPO4 (w/w) (pH 7.0) was selected for extracting active plasma proteins directly from pig plasma. As a result, recovery rates as high as 95.7% for IgG and 93.0% for albumin were achieved. In addition, some contaminating proteins were also removed by this system, which may provide a new alternative method for the separation and purification of immunoglobulin. PMID- 26827282 TI - Quantitative structure retention/activity relationships of biologically relevant 4-amino-7-chloroquinoline based compounds. AB - The chromatographic behaviour of series of 4-amino-7-chloroquinoline (4,7-ACQ) based compounds was studied by reversed-phase thin-layer chromatography (RPTLC) with binary mobile phases containing water and the organic modifiers, DMSO or acetone. The lipophilicity of the studied compounds was determined by extrapolation of retention parameters RM to pure water content in mobile phase. In order to obtain some basic insight into the chromatographic behaviour and structural features of investigated compounds, PCA was performed on both chromatographic data (RM values) and calculated 2D and 3D structural descriptors. Both QSRR and QSAR models were built by means of the partial least squares (PLS) statistical method. It was found that descriptors which encode hydrophobic (dispersive) interactions have positive influence on retention, while influence of descriptors encoding polar interactions was negative. According to the obtained PLS model for inhibition of botulinum neurotoxin serotype A light chain, hydrophobic interactions influence positively on the mechanism of action of the investigated 4,7-ACQ, while polar interactions are less favoured. Contrary, the results of PLS modelling of activity against Plasmodium falciparum strains (W2, D6 and TM91C235) indicate that higher polarity of 4,7-ACQ contribute to their higher antimalarial activity. PMID- 26827283 TI - Actin flows in cell migration: from locomotion and polarity to trajectories. AB - Eukaryotic cell movement is characterized by very diverse migration modes. Recent studies show that cells can adapt to environmental cues, such as adhesion and geometric confinement, thereby readily switching their mode of migration. Among this diversity of motile behavior, actin flows have emerged as a highly conserved feature of both mesenchymal and amoeboid migration, and have also been identified as key regulators of cell polarity. This suggests that the various observed migration modes are continuous variations of elementary locomotion mechanisms, based on a very robust physical property of the actin/myosin system - its ability to sustain flows at the cell scale. This central role of actin/myosin flows is shown to affect the large scale properties of cell trajectories. PMID- 26827285 TI - Structure and mechanism of nucleases regulated by SLX4. AB - SLX4 is a multidomain platform that regulates various proteins that are involved in genome maintenance and stability. Among these proteins are three structure selective nucleases (SSEs). XPF-ERCC1 and MUS81-EME1 are structurally similar and function as heterodimers of highly similar subunits, in which only one is active. Two independent modules are formed from subunits of the heterodimers - a dimer of nuclease and nuclease-like domains and a dimer of tandem helix-hairpin-helix HhH2 domains. Both modules are responsible for substrate recognition. The third SSE, SLX1, contains GIY-YIG and RING domains and is a promiscuous nuclease. Structural data imply that SLX1 exists in free form as an autoinhibited homodimer. Association with SLX4 platform disrupts the homodimer and activates SLX1. This review discusses the available structural and mechanistic information on SLX4 regulated SSEs. PMID- 26827287 TI - Lysosomal signaling in control of degradation pathways. AB - Autophagy mediates the (non-)selective bulk degradation of cytoplasm, protein aggregates, damaged organelles and certain pathogens. The endosomal membrane system uses multivesicular bodies (MVBs) to selectively deliver ubiquitinated membrane proteins together with extracellular components into lysosomes. Microautophagy (MA) and chaperone-mediated autophagy (CMA) additionally contribute to the selective delivery of cargo into lysosomes. The coordinated function of these lysosomal degradation pathways is essential to maintain cellular homeostasis. Their activity is controlled by mTOR (mammalian target of rapamycin) signaling and thus coupled to metabolic processes during cell growth. Here, we will discuss how TORC1 on lysosomes and TORC2 at the plasma membrane coordinate the different membrane biogenesis pathways with cargo selection, vesicle transport and fusion with lysosomes in response to intracellular and extracellular cues. PMID- 26827286 TI - Effect of hospital size and on-call arrangements on intrapartum and early neonatal mortality among low-risk newborns in Finland. AB - OBJECTIVE: To evaluate the influence of delivery unit size and on-call staffing in the performance of low-risk deliveries in Finland. STUDY DESIGN: A population based study of hospital size and level based on Medical Birth Register data. Population was all hospital births in Finland in 2005-2009. Inclusion criteria were singleton births (birth weight 2500g or more) without major congenital anomalies or birth defects. Additionally, only intrapartum stillbirths were included. Birthweights and maternal background characteristics were adjusted for by logistic regression. Main outcome measures were intrapartum or early neonatal mortality, neonatal asphyxia and newborns' need for intensive care or transfer to other hospital and longer duration of care. On-call arrangements were asked from each of the hospitals. RESULTS: Intrapartum mortality was higher in units where physicians were at home when on-call (OR 1.25; 95% CI 1.02-1.52). A tendency to a higher mortality was also recorded in non-university hospitals (OR 1.18; 95% CI 0.99-1.40). Early neonatal mortality was twofold in units with less than 1000 births annually (OR 2.11; 95% CI 0.97-4.56) and in units where physicians were at home when on-call (OR 1.85; 95% CI 0.91-3.76). These results did not reach statistical significance. No differences between the units were found regarding Apgar scores or umbilical cord pH. CONCLUSION: The differences in mortality rates between different level hospitals suggest that adverse outcomes during delivery should be studied in detail in relation to hospital characteristics, such as size or level, and more international studies determining obstetric patient safety indicators are required. PMID- 26827284 TI - The role of ATP-dependent machines in regulating genome topology. AB - All cells must copy and express genes in accord with internal and external cues. The proper timing and response of such events relies on the active control of higher-order genomic organization. Cells use ATP-dependent molecular machines to alter the local and global topology of DNA so as to promote and counteract the persistent effects of transcription and replication. X-ray crystallography and electron microscopy, coupled with biochemical and single molecule methods are continuing to provide a wealth of mechanistic information on how DNA remodeling factors are employed to dynamically shape and organize the genome. PMID- 26827288 TI - The dynamic subcellular localization of ERK: mechanisms of translocation and role in various organelles. AB - The dynamic subcellular localization of ERK in resting and stimulated cells plays an important role in its regulation. In resting cells, ERK localizes in the cytoplasm, and upon stimulation, it translocates to its target substrates and organelles. ERK signaling initiated from different places in resting cells has distinct outcomes. In this review, we summarize the mechanisms of ERK1/2 translocation to the nucleus and mitochondria, and of ERK1c to the Golgi. We also show that ERK1/2 translocation to the nucleus is a useful anti cancer target. Unraveling the complex subcellular localization of ERK and its dynamic changes upon stimulation provides a better understanding of the regulation of ERK signaling and may result in the development of new strategies to combat ERK related diseases. PMID- 26827290 TI - Improvement of the antifungal activity of lactic acid bacteria by addition to the growth medium of phenylpyruvic acid, a precursor of phenyllactic acid. AB - The aim of the current study was to improve the antifungal activity of eight lactic acid bacterial (LAB) strains by the addition of phenylpyruvic acid (PPA), a precursor of the antifungal compound phenyllactic acid (PLA), to a defined growth medium (DM). The effect of PPA addition on the LABs antifungal activity related to the production of organic acids (PLA, d-lactic, l-lactic, acetic, citric, formic and 4-hydroxy-phenyllactic acids) and of other phenylpyruvic derived molecules, was investigated. In the presence of PPA the inhibitory activity (expressed as growth inhibition percentage) against fungal bread contaminants Aspergillus niger and Penicillium roqueforti significantly increased and was, even if not completely, associated to PLA increase (from a mean value of 0.44 to 0.93 mM). While the inhibitory activity against Endomyces fibuliger was mainly correlated to the low pH and to lactic, acetic and p-OH-PLA acids. When the PCA analysis based on data of growth inhibition percentage and organic acid concentrations was performed, strains grown in DM+PPA separated from those grown in DM and the most active strains Lactobacillus plantarum 21B, Lactobacillus fermentum 18B and Lactobacillus brevis 18F grouped together. The antifungal activity resulted to be strain-related, based on a different mechanism of action for filamentous fungi and the yeast and was not exclusively associated to the increase of PLA. Therefore, a further investigation on the unique unidentified peak in HPLC-UV chromatograms, was performed by LC-MS/MS analysis. Actually, full scan mass spectra (negative ion mode) recorded at the retention time of the unknown compound, showed a main peak of m/z 291.0 which was consistent with the nominal mass of the molecular ion [M-H](-) of polyporic acid, a PPA derivative whose antifungal activity has been previously reported (Brewer et al., 1977). In conclusion, the addition of PPA to the growth medium contributed to improve the antifungal activity of LAB strains and resulted in the production of the polyporic acid, here ascertained in LAB strains. PMID- 26827291 TI - Comparative proteomic analysis of a potentially probiotic Lactobacillus pentosus MP-10 for the identification of key proteins involved in antibiotic resistance and biocide tolerance. AB - Probiotic bacterial cultures require resistance mechanisms to avoid stress related responses under challenging environmental conditions; however, understanding these traits is required to discern their utility in fermentative food preparations, versus clinical and agricultural risk. Here, we compared the proteomic responses of Lactobacillus pentosus MP-10, a potentially probiotic lactic acid bacteria isolated from brines of naturally fermented Alorena green table olives, exposed to sub-lethal concentrations of antibiotics (amoxicillin, chloramphenicol and tetracycline) and biocides (benzalkonium chloride and triclosan). Several genes became differentially expressed depending on antimicrobial exposure, such as the up-regulation of protein synthesis, and the down-regulation of carbohydrate metabolism and energy production. The antimicrobials appeared to have altered Lb. pentosus MP-10 physiology to achieve a gain of cellular energy for survival. For example, biocide-adapted Lb. pentosus MP-10 exhibited a down-regulated phosphocarrier protein HPr and an unexpressed oxidoreductase. However, protein synthesis was over-expressed in antibiotic- and biocide-adapted cells (ribosomal proteins and glutamyl-tRNA synthetase), possibly to compensate for damaged proteins targeted by antimicrobials. Furthermore, stress proteins, such as NADH peroxidase (Npx) and a small heat shock protein, were only over-expressed in antibiotic-adapted Lb. pentosus MP-10. Results showed that adaptation to sub-lethal concentrations of antimicrobials could be a good way to achieve desirable robustness of the probiotic Lb. pentosus MP-10 to various environmental and gastrointestinal conditions (e.g., acid and bile stresses). PMID- 26827289 TI - A Novel Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (GSK1278863) for Anemia in CKD: A 28-Day, Phase 2A Randomized Trial. AB - BACKGROUND: Anemia associated with chronic kidney disease (CKD) often requires treatment with recombinant human erythropoietin (EPO). Hypoxia-inducible factor prolyl hydroxylase inhibitors (PHIs) stimulate endogenous EPO synthesis and induce effective erythropoiesis by non-EPO effects. GSK1278863 is an orally administered small-molecule PHI. STUDY DESIGN: Multicenter, single-blind, randomized, placebo-controlled, parallel-group study. SETTING & PARTICIPANTS: Anemic non-dialysis-dependent patients with CKD stages 3-5 (CKD-3/4/5 group; n=70) and anemic hemodialysis patients with CKD stage 5D (CKD-5D group; n=37). INTERVENTIONS: Patients with CKD-3/4/5 received placebo or GSK1278863 (10, 25, 50, or 100mg), and patients with CKD-5D received placebo or GSK1278863 (10 or 25mg) once daily for 28 days. OUTCOMES & MEASUREMENTS: Primary pharmacokinetic and pharmacodynamic (increase and response rates in achieving the target hemoglobin [Hb] concentration, plasma EPO concentrations, reticulocyte count, and others]) and safety and tolerability end points were obtained. RESULTS: Both CKD 3/4/5 and CKD-5D populations showed a dose-dependent increase in EPO concentrations and consequent increases in reticulocytes and Hb levels. Percentages of GSK1278863 participants with an Hb level increase > 1.0g/dL (CKD 3/4/5) and >0.5g/dL (CKD-5D) were 63% to 91% and 71% to 89%, respectively. Per protocol-defined criteria, high rate of increase in Hb level, or high absolute Hb value was the main cause for withdrawal (CKD-3/4/5, 30%; CKD-5D, 22%). A dose dependent decrease in hepcidin levels and increase in total and unsaturated iron binding were observed in all GSK1278863-treated patients. LIMITATIONS: Sparse pharmacokinetic sampling may have limited covariate characterization. EPO concentrations at the last pharmacodynamic sample (5-6 hours) postdose may not represent peak concentrations, which occurred 8 to 10 hours postdose in previous studies. Patients were not stratified by diabetes status, potentially confounding vascular endothelial growth factor and glucose analyses. CONCLUSIONS: GSK1278863 induced an effective EPO response and stimulated non-EPO mechanisms for erythropoiesis in anemic non-dialysis-dependent and dialysis-dependent patients with CKD. PMID- 26827292 TI - Sexual-orientation differences in drinking patterns and use of drinking contexts among college students. AB - BACKGROUND: Evidence suggests there are important sexual-orientation differences in alcohol consumption, particularly among women. Little is known about where gay/lesbian and bisexual college students drink or differences in drinking patterns derived from graduated frequency measures between heterosexual, gay/lesbian, and bisexual students. The goal of this analysis was to examine patterns of alcohol consumption-including drinking prevalence, quantity, frequency, and contexts of use-by sexual orientation. METHODS: Data on sexual identity, gender, drinking behaviors, and drinking contexts were examined from repeated cross-sectional samples of undergraduate students attending 14 public California universities from 2003-2011 (n=58,903). Multivariable statistical techniques were employed to examine sexual-orientation differences stratified by gender. RESULTS: Gay males, lesbians, and bisexual females were significantly more likely to report drinking alcohol in the current semester than their same gender heterosexual peers (relative risks ranged from 1.07 to 1.10, p-values <0.01). Among current drinkers, bisexual females consumed 7 or more drinks and lesbians consumed 10 or more drinks on significantly more days than heterosexual females. On the other hand, gay male drinkers consumed 8 or more drinks on significantly fewer days than heterosexual male drinkers. Compared to their same gender heterosexual peers: lesbian/gay and bisexual students drank less frequently at Greek parties (incidence rate ratios [IRRs] ranged from 0.52 to 0.73, p-values <0.01); lesbians (IRR=0.84, p=0.043) and bisexual males (IRR=0.82, p=0.009) drank less frequently at off-campus parties; and gay males drank more frequently outdoors (IRR=1.63, p<0.001) and at bars/restaurants (IRR=1.21, p=0.013). CONCLUSIONS: Alcohol prevention programs and future research should consider sexual-orientation differences in drinking patterns and use of drinking contexts. PMID- 26827293 TI - A randomized clinical trial of a tailored behavioral smoking cessation preparation program. AB - Despite considerable progress in reducing cigarette smoking prevalence and enhancing smoking cessation treatments, most smokers who attempt to quit relapse. The current randomized clinical trial evaluated the efficacy of an adjunctive behavioral smoking cessation treatment based on learning theory. Adult daily smokers were randomly assigned to standard treatment (N = 47) with nicotine patch and individual counseling or to standard treatment plus a "practice quitting" program involving seven sessions of escalating prescribed abstinence periods (N = 46) prior to a target stop smoking date. Practice quitting was designed to extinguish smoking in response to withdrawal symptoms. Retention in treatment was excellent and the treatment manipulation increased the interval between cigarettes across practice quitting sessions on average by 400%. The primary endpoint, seven-day point-prevalence abstinence four weeks post-quit, was not significantly affected by practice quitting (31.9% in the standard treatment condition, 37.0% in the practice quitting condition). Practice quitting increased latency to a first lapse among those who quit smoking for at least one day and prevented progression from a first lapse to relapse (smoking daily for a week) relative to standard treatment, however. Practice quitting is a promising adjunctive treatment in need of refinement to enhance adherence and efficacy. PMID- 26827294 TI - The effect of oxytocin on the anthropomorphism of touch. AB - One of the leading hypotheses regarding the mechanism underlying the social effects of oxytocin (OT) is the "social salience hypothesis", which proposes that OT alters the attentional salience of social cues in a context-dependent manner. Recently, OT was implicated in the process of anthropomorphism; specifically, OT was found to increase the tendency to ascribe social meaning to inanimate stimuli. However, the precise component of social interaction that contributes to this effect remains unclear. Because OT plays a role in the response to touch, whether or not objects are touching in a social context may represent the prominent trigger. Given that OT plays a major role in both anthropomorphism and touch, it is reasonable to assume that OT enhances anthropomorphism specifically for non-human touch, further clarifying its role in altering the perceptual salience of social cues. Here, we examined whether intranasal delivery of OT influences anthropomorphism for touch in inanimate objects. To that end, we implicitly measured the emotional reactions of participants (N=51) to photos that depicted two humans or two inanimate objects either touching or not touching. We asked them to rate whether they will include each photo in an emotional album and found that OT treatment increased the likelihood of inclusion in an emotional album to photos that contain touch, particularly between inanimate objects. In a follow-up experiment we found that the more human the inanimate objects were perceived, the more included they were in the emotional album. Our findings demonstrate that OT can enhance the social meaning of touch between two inanimate objects and advance our understanding of the mechanisms underlying the ability of OT to anthropomorphize environmental cues. PMID- 26827296 TI - Complexation and molecular modeling studies of europium(III)-gallic acid-amino acid complexes. AB - With many metal-based drugs extensively used today in the treatment of cancer, attention has focused on the development of new coordination compounds with antitumor activity with europium(III) complexes recently introduced as novel anticancer drugs. The aim of this work is to design new Eu(III) complexes with gallic acid, an antioxida'nt phenolic compound. Gallic acid was chosen because it shows anticancer activity without harming health cells. As antioxidant, it helps to protect human cells against oxidative damage that implicated in DNA damage, cancer, and accelerated cell aging. In this work, the formation of binary and ternary complexes of Eu(III) with gallic acid, primary ligand, and amino acids alanine, leucine, isoleucine, and tryptophan was studied by glass electrode potentiometry in aqueous solution containing 0.1M NaNO3 at (298.2 +/- 0.1) K. Their overall stability constants were evaluated and the concentration distributions of the complex species in solution were calculated. The protonation constants of gallic acid and amino acids were also determined at our experimental conditions and compared with those predicted by using conductor-like screening model for realistic solvation (COSMO-RS) model. The geometries of Eu(III)-gallic acid complexes were characterized by the density functional theory (DFT). The spectroscopic UV-visible and photoluminescence measurements are carried out to confirm the formation of Eu(III)-gallic acid complexes in aqueous solutions. PMID- 26827295 TI - Androstadienone's influence on the perception of facial and vocal attractiveness is not sex specific. AB - The androgen steroid androstadienone, an odorous compound emitted from the human axillary region, has recurrently been considered as a candidate compound involved in human chemical communication and mate choice. Although perception of androstadienone has been shown to influence several affective (mood), attentional, physiological and neural parameters, studies investigating its impact on human attractiveness remain unpersuasive because of incomplete designs (e.g., only female participants) and contradictory results. The aim of this study was to investigate how androstadienone may influence others' attractiveness. Specifically, we used a complete design (male and female raters, male and female faces and voices) to determine whether androstadienone influences the perception of social stimuli in a sex-specific manner, which would favor pheromonal-like properties of the compound, or in a more general manner, which would suggest that the compound has broader influences on human psychological responses. After comparing the ratings of men and women who were exposed to androstadienone masked in clove oil with those of men and women who were exposed to clove oil alone, we found that androstadienone enhanced the perceived attractiveness of emotionally relevant stimuli (opposite-sex stimuli in men and in fertile women). Response times for categorizing the stimuli as attractive or not were also affected by androstadienone, with longer response times in men and in fertile women and shorter response times in non-fertile women, irrespective of the stimulus sex. The results favor the hypothesis of general effects over sex-specific effects of androstadienone, thus questioning the relevance of focusing on that particular compound in the study of human attractiveness through body odor and encouraging the search for other semiochemicals that might be significant for human mate choice. PMID- 26827297 TI - SUDEP: To discuss or not? Recommendations from bereaved relatives. AB - PURPOSE: The overarching purpose of this descriptive and exploratory qualitative study was to understand the experiences of relatives of individuals whose deaths were identified as SUDEP and to explore their preferences regarding SUDEP counseling. METHODS: The principles of fundamental qualitative description informed all design decisions. Stratified purposeful sampling included 27 bereaved relatives (parent, sibling, spouse or child), aged at least 18 years, of 21 persons who passed away because of SUDEP. In-depth one-to-one interviews were conducted. Directed content analysis was used to code, categorize, and synthesize the interview data. RESULTS: There was consensus among all participants that the risk of SUDEP should be discussed with patients by their healthcare providers. Relatives opted for information on SUDEP at the time of, or shortly following, the diagnosis of epilepsy. Neurologists were identified as the healthcare providers who should discuss SUDEP with patients during a face-to-face encounter, subsequently supplemented with written information. It was identified that, when discussing SUDEP, emphasis should be on the risk factors, possible preventive strategies, and the rarity of incidence. CONCLUSION: The results of this study indicated that bereaved relatives wanted neurologists to inform patients about the risk of SUDEP, with optimal timing and setting of SUDEP counseling determined on a case-by-case basis. PMID- 26827298 TI - Anticonvulsant activity of beta-caryophyllene against pentylenetetrazol-induced seizures. AB - Increasing evidence suggests that plant-derived extracts and their isolated components are useful for treatment of seizures and, hence, constitute a valuable source of new antiepileptic drugs with improved efficacy and better adverse effect profile. beta-Caryophyllene is a natural bicyclic sesquiterpene that occurs in a wide range of plant species and displays a number of biological actions, including neuroprotective activity. In the present study, we tested the hypothesis that beta-caryophyllene displays anticonvulsant effects. In addition, we investigated the effect of beta-caryophyllene on behavioral parameters and on seizure-induced oxidative stress. Adult C57BL/6 mice received increasing doses of beta-caryophyllene (0, 10, 30, or 100mg/kg). After 60 min, we measured the latencies to myoclonic and generalized seizures induced by pentylenetetrazole (PTZ, 60 mg/kg). We found that beta-caryophyllene increased the latency to myoclonic jerks induced by PTZ. This result was confirmed by electroencephalographic analysis. In a separate set of experiments, we found that mice treated with an anticonvulsant dose of beta-caryophyllene (100mg/kg) displayed an improved recognition index in the object recognition test. This effect was not accompanied by behavioral changes in the open-field, rotarod, or forced swim tests. Administration of an anticonvulsant dose of beta-caryophyllene (100mg/kg) did not prevent PTZ-induced oxidative stress (i.e., increase in the levels of thiobarbituric acid-reactive substances or the decrease in nonprotein thiols content). Altogether, the present data suggest that beta-caryophyllene displays anticonvulsant activity against seizures induced by PTZ in mice. Since no adverse effects were observed in the same dose range of the anticonvulsant effect, beta-caryophyllene should be further evaluated in future development of new anticonvulsant drugs. PMID- 26827299 TI - Changing the approach to treatment choice in epilepsy using big data. AB - PURPOSE: A UCB-IBM collaboration explored the application of machine learning to large claims databases to construct an algorithm for antiepileptic drug (AED) choice for individual patients. METHODS: Claims data were collected between January 2006 and September 2011 for patients with epilepsy > 16 years of age. A subset of patient claims with a valid index date of AED treatment change (new, add, or switch) were used to train the AED prediction model by retrospectively evaluating an index date treatment for subsequent treatment change. Based on the trained model, a model-predicted AED regimen with the lowest likelihood of treatment change was assigned to each patient in the group of test claims, and outcomes were evaluated to test model validity. RESULTS: The model had 72% area under receiver operator characteristic curve, indicating good predictive power. Patients who were given the model-predicted AED regimen had significantly longer survival rates (time until a treatment change event) and lower expected health resource utilization on average than those who received another treatment. The actual prescribed AED regimen at the index date matched the model-predicted AED regimen in only 13% of cases; there were large discrepancies in the frequency of use of certain AEDs/combinations between model-predicted AED regimens and those actually prescribed. CONCLUSIONS: Chances of treatment success were improved if patients received the model-predicted treatment. Using the model's prediction system may enable personalized, evidence-based epilepsy care, accelerating the match between patients and their ideal therapy, thereby delivering significantly better health outcomes for patients and providing health-care savings by applying resources more efficiently. Our goal will be to strengthen the predictive power of the model by integrating diverse data sets and potentially moving to prospective data collection. PMID- 26827300 TI - Psychiatric comorbidities in patients from seven families with autosomal dominant cortical tremor, myoclonus, and epilepsy. AB - OBJECTIVE: The objective of this report was to assess the psychiatric comorbidity in a group of patients affected by autosomal dominant cortical tremor, myoclonus, and epilepsy (ADCME). METHODS: Reliable and validated psychodiagnostic scales including the BDI (Beck Depression Inventory), STAI-Y1 and 2 (State-Trait Anxiety Inventory - Y; 1 and 2), MMPI-2 (Minnesota Multiphasic Personality Inventory - 2), and QoLIE-31 (Quality of Life in Epilepsy Inventory - 31) were administered to 20 patients with ADCME, 20 patients with juvenile myoclonic epilepsy (JME), and 20 healthy controls. RESULTS: There was a higher prevalence of mood disorders in patients with ADCME compared to patients with JME and healthy controls, particularly depression (p=0.035 and p=0.017, respectively) and state anxiety (p=0.024 and p=0.019, respectively). Trait anxiety was not different from JME (p=0.102) but higher than healthy controls (p=0.017). The myoclonus score positively correlated with both state (rho: 0.58, p=0.042) and trait anxiety (rho: 0.65, p=0.011). These psychiatric features were also often associated with pathological traits of personality: paranoid (OR: 25.7, p=0.003), psychasthenia (OR: 7.0, p=0.023), schizophrenia (OR: 8.5, p=0.011), and hypomania (OR: 5.5, p=0.022). Finally, in patients with ADCME, decreased quality of life correlated with these psychiatric symptoms. SIGNIFICANCE: Patients with ADCME show a significant psychiatric burden that impairs their quality of life. A comprehensive psychiatric evaluation should be offered at the time of diagnosis to detect these comorbidities and to treat them. PMID- 26827302 TI - Contributed Review: Distributed optical fibre dynamic strain sensing. AB - Extensive research on Brillouin- and Raman-based distributed optical fibre sensors over the past two decades has resulted in the commercialization of distributed sensors capable of measuring static and quasi-static phenomena such as temperature and strain. Recently, the focus has been shifted towards developing distributed sensors for measurement of dynamic phenomena such as dynamic strain and sound waves. This article reviews the current state of the art distributed optical fibre sensors capable of quantifying dynamic vibrations. The most important aspect of Rayleigh and Brillouin scattering processes which have been used for distributed dynamic measurement are studied. The principle of the sensing techniques used to measure dynamic perturbations are analyzed followed by a case study of the most recent advances in this field. It is shown that the Rayleigh-based sensors have longer sensing range and higher frequency range, but their spatial resolution is limited to 1 m. On the other hand, the Brillouin based sensors have shown a higher spatial resolution, but relatively lower frequency and sensing ranges. PMID- 26827301 TI - Invited Article: High resolution angle resolved photoemission with tabletop 11 eV laser. AB - We developed a table-top vacuum ultraviolet (VUV) laser with 113.778 nm wavelength (10.897 eV) and demonstrated its viability as a photon source for high resolution angle-resolved photoemission spectroscopy (ARPES). This sub-nanosecond pulsed VUV laser operates at a repetition rate of 10 MHz, provides a flux of 2 * 10(12) photons/s, and enables photoemission with energy and momentum resolutions better than 2 meV and 0.012 A(-1), respectively. Space-charge induced energy shifts and spectral broadenings can be reduced below 2 meV. The setup reaches electron momenta up to 1.2 A(-1), granting full access to the first Brillouin zone of most materials. Control over the linear polarization, repetition rate, and photon flux of the VUV source facilitates ARPES investigations of a broad range of quantum materials, bridging the application gap between contemporary low energy laser-based ARPES and synchrotron-based ARPES. We describe the principles and operational characteristics of this source and showcase its performance for rare earth metal tritellurides, high temperature cuprate superconductors, and iron-based superconductors. PMID- 26827303 TI - Tunable diode laser absorption spectroscopy-based tomography system for on-line monitoring of two-dimensional distributions of temperature and H2O mole fraction. AB - To monitor two-dimensional (2D) distributions of temperature and H2O mole fraction, an on-line tomography system based on tunable diode laser absorption spectroscopy (TDLAS) was developed. To the best of the authors' knowledge, this is the first report on a multi-view TDLAS-based system for simultaneous tomographic visualization of temperature and H2O mole fraction in real time. The system consists of two distributed feedback (DFB) laser diodes, a tomographic sensor, electronic circuits, and a computer. The central frequencies of the two DFB laser diodes are at 7444.36 cm(-1) (1343.3 nm) and 7185.6 cm(-1) (1391.67 nm), respectively. The tomographic sensor is used to generate fan-beam illumination from five views and to produce 60 ray measurements. The electronic circuits not only provide stable temperature and precise current controlling signals for the laser diodes but also can accurately sample the transmitted laser intensities and extract integrated absorbances in real time. Finally, the integrated absorbances are transferred to the computer, in which the 2D distributions of temperature and H2O mole fraction are reconstructed by using a modified Landweber algorithm. In the experiments, the TDLAS-based tomography system was validated by using asymmetric premixed flames with fixed and time varying equivalent ratios, respectively. The results demonstrate that the system is able to reconstruct the profiles of the 2D distributions of temperature and H2O mole fraction of the flame and effectively capture the dynamics of the combustion process, which exhibits good potential for flame monitoring and on line combustion diagnosis. PMID- 26827304 TI - The role of mode match in fiber cavities. AB - We study and realize asymmetric fiber-based cavities with optimized mode match to achieve high reflectivity on resonance. This is especially important for mutually coupling two physical systems via light fields, e.g., in quantum hybrid systems. Our detailed theoretical and experimental analysis reveals that on resonance, the interference effect between the directly reflected non-modematched light and the light leaking back out of the cavity can lead to large unexpected losses due to the mode filtering of the incoupling fiber. Strong restrictions for the cavity design result out of this effect and we show that planar-concave cavities are clearly best suited. We validate our analytical model using numerical calculations and demonstrate an experimental realization of an asymmetric fiber Fabry-Perot cavity with optimized parameters. PMID- 26827305 TI - Defect detection inside superconducting 1.3 GHz cavities by means of x-ray fluorescence spectroscopy. AB - X-ray fluorescence probe for detection of foreign material inclusions on the inner surface of superconducting cavities has been developed and tested. The setup detects trace element content such as a few micrograms of impurities responsible for thermal breakdown phenomena limiting the cavity performance. The setup has been customized for the geometry of 1.3 GHz TESLA-type niobium cavities and focuses on the surface of equator area at around 103 mm from the centre axis of the cavities with around 20 mm detection spot. More precise localization of inclusions can be reconstructed by means of angular or lateral displacement of the cavity. Preliminary tests confirmed a very low detection limit for elements laying in the high efficiency spectrum zone (from 5 to 10 keV), and a high angular resolution allowing an accurate localization of defects within the equator surface. PMID- 26827306 TI - Steady-state photoluminescent excitation characterization of semiconductor carrier recombination. AB - Photoluminescence excitation spectroscopy is a contactless characterization technique that can provide valuable information about the surface and bulk recombination parameters of a semiconductor device, distinct from other sorts of photoluminescent measurements. For this technique, a temperature-tuned light emitting diode (LED) has several advantages over other light sources. The large radiation density offered by LEDs from near-infrared to ultraviolet region at a low cost enables efficient and fast photoluminescence measurements. A simple and inexpensive LED-based setup facilitates measurement of surface recombination velocity and bulk Shockley-Read-Hall lifetime, which are key parameters to assess device performance. Under the right conditions, this technique can also provide a contactless way to measure the external quantum efficiency of a solar cell. PMID- 26827307 TI - Doping He droplets by laser ablation with a pulsed supersonic jet source. AB - Laser ablation offers the possibility to study a rich number of atoms, molecules, and clusters in the gas phase. By attaching laser ablated materials to helium nanodroplets, one can gain highly resolved spectra of isolated species in a cold, weakly perturbed system. Here, we present a new setup for doping pulsed helium nanodroplet beams by means of laser ablation. In comparison to more well established techniques using a continuous nozzle, pulsed nozzles show significant differences in the doping efficiency depending on certain experimental parameters (e.g., position of the ablation plume with respect to the droplet formation, nozzle design, and expansion conditions). In particular, we demonstrate that when the ablation region overlaps with the droplet formation region, one also creates a supersonic beam of helium atoms seeded with the sample material. The processes are characterized using a surface ionization detector. The overall doping signal is compared to that of conventional oven cell doping showing very similar dependence on helium stagnation conditions, indicating a comparable doping process. Finally, the ablated material was spectroscopically studied via laser induced fluorescence. PMID- 26827308 TI - Heating system of pellet samples integrated with terahertz spectrometer. AB - This article describes automation of temperature-dependent terahertz spectroscopic experiments. The proposed dual-heater temperature controller based on a cascade proportional-integral-derivative algorithm provides smooth temperature changes in the polyethylene-based pharmaceutical pellet samples. The device has been integrated with a terahertz time-domain spectrometer. Thermodynamic experiments can now be performed without any probe inserted into the measured sample. Selected results of temperature-induced evolution in terahertz spectra are presented. PMID- 26827309 TI - Simultaneous streak and frame interferometry for electron density measurements of laser produced plasmas. AB - A system of two collinear probe beams with different wavelengths and pulse durations was used to capture simultaneously snapshot interferograms and streaked interferograms of laser produced plasmas. The snapshots measured the two dimensional, path-integrated, electron density on a charge-coupled device while the radial temporal evolution of a one dimensional plasma slice was recorded by a streak camera. This dual-probe combination allowed us to select plasmas that were uniform and axisymmetric along the laser direction suitable for retrieving the continuous evolution of the radial electron density of homogeneous plasmas. Demonstration of this double probe system was done by measuring rapidly evolving plasmas on time scales less than 1 ns produced by the interaction of femtosecond, high intensity, laser pulses with argon gas clusters. Experiments aimed at studying homogeneous plasmas from high intensity laser-gas or laser-cluster interaction could benefit from the use of this probing scheme. PMID- 26827310 TI - Design of a finger base-type pulse oximeter. AB - A pulse oximeter is a common medical instrument used for noninvasively monitoring arterial oxygen saturation (SpO2). Currently, the fingertip-type pulse oximeter is the prevalent type of pulse oximeter used. However, it is inconvenient for long-term monitoring, such as that under motion. In this study, a wearable and wireless finger base-type pulse oximeter was designed and implemented using the tissue optical simulation technique and the Monte Carlo method. The results revealed that a design involving placing the light source at 135 degrees -165 degrees and placing the detector at 75 degrees -90 degrees or 90 degrees -105 degrees yields the optimal conditions for measuring SpO2. Finally, the wearable and wireless finger base-type pulse oximeter was implemented and compared with the commercial fingertip-type pulse oximeter. The experimental results showed that the proposed optimal finger base-type pulse oximeter design can facilitate precise SpO2 measurement. PMID- 26827311 TI - A tandem time-of-flight spectrometer for negative-ion/positive-ion coincidence measurements with soft x-ray excitation. AB - We present a newly constructed spectrometer for negative-ion/positive-ion coincidence spectroscopy of gaseous samples. The instrument consists of two time of-flight ion spectrometers and a magnetic momentum filter for deflection of electrons. The instrument can measure double and triple coincidences between mass resolved negative and positive ions with high detection efficiency. First results include identification of several negative-ion/positive-ion coincidence channels following inner-shell photoexcitation of sulfur hexafluoride (SF6). PMID- 26827312 TI - Convenient determination of luminescence quantum yield using a combined electronic absorption and emission spectrometer. AB - It is possible to measure luminescence quantum yield in a facile way, by designing an optical spectrometer capable of obtaining electronic absorption as well as luminescence spectra, with a setup that uses the same light source and detector for both the spectral measurements. Employment of a single light source and single detector enables use of the same correction factor profile for spectral corrections. A suitable instrumental scaling factor is used for adjusting spectral losses. PMID- 26827313 TI - Analysis of ionic photofragments stored in an electrostatic storage ring. AB - A new method to analyze the properties of fragment ions created in storage ring experiments is presented. The technique relies on an acceleration of ionic fragments immediately after production whereby the fragments are stored in the storage ring. To obtain a fragment mass spectrum, the storage ring is exploited as an electrostatic analyzer (ESA) in which case the number of stored fragment ions is recorded as a function of the applied acceleration potential. However, the storage ring can additionally be employed as a time-of-flight (TOF) instrument by registering the temporal distribution of fragment ions. It is demonstrated that the combined ESA-TOF operation of the ring allows not only to determine fragment masses with much better resolution compared to the ESA mode alone but also enables the extraction of detailed information on the fragmentation dynamics. The method is described analytically and verified with photodissociation experiments on stored Cl2 (-) at an excitation wavelength of 530 nm. PMID- 26827314 TI - Improved neutron-gamma discrimination for a (6)Li-glass neutron detector using digital signal analysis methods. AB - A (6)Li-glass scintillator (GS20) based neutron Anger camera was developed for time-of-flight single-crystal diffraction instruments at Spallation Neutron Source. Traditional Pulse-Height Analysis (PHA) for Neutron-Gamma Discrimination (NGD) resulted in the neutron-gamma efficiency ratio (defined as NGD ratio) on the order of 10(4). The NGD ratios of Anger cameras need to be improved for broader applications including neutron reflectometers. For this purpose, six digital signal analysis methods of individual waveforms acquired from photomultiplier tubes were proposed using (i) charge integration, (ii) pulse amplitude histograms, (iii) power spectrum analysis combined with the maximum pulse-amplitude, (iv) two event parameters (a1, b0) obtained from a Wiener filter, (v) an effective amplitude (m) obtained from an adaptive least-mean square filter, and (vi) a cross-correlation coefficient between individual and reference waveforms. The NGD ratios are about 70 times those from the traditional PHA method. Our results indicate the NGD capabilities of neutron Anger cameras based on GS20 scintillators can be significantly improved with digital signal analysis methods. PMID- 26827316 TI - Evaluation of reconstruction errors and identification of artefacts for JET gamma and neutron tomography. AB - The Joint European Torus (JET) neutron profile monitor ensures 2D coverage of the gamma and neutron emissive region that enables tomographic reconstruction. Due to the availability of only two projection angles and to the coarse sampling, tomographic inversion is a limited data set problem. Several techniques have been developed for tomographic reconstruction of the 2-D gamma and neutron emissivity on JET, but the problem of evaluating the errors associated with the reconstructed emissivity profile is still open. The reconstruction technique based on the maximum likelihood principle, that proved already to be a powerful tool for JET tomography, has been used to develop a method for the numerical evaluation of the statistical properties of the uncertainties in gamma and neutron emissivity reconstructions. The image covariance calculation takes into account the additional techniques introduced in the reconstruction process for tackling with the limited data set (projection resampling, smoothness regularization depending on magnetic field). The method has been validated by numerically simulations and applied to JET data. Different sources of artefacts that may significantly influence the quality of reconstructions and the accuracy of variance calculation have been identified. PMID- 26827315 TI - Measurement of toroidal vessel eddy current during plasma disruption on J-TEXT. AB - In this paper, we have employed a thin, printed circuit board eddy current array in order to determine the radial distribution of the azimuthal component of the eddy current density at the surface of a steel plate. The eddy current in the steel plate can be calculated by analytical methods under the simplifying assumptions that the steel plate is infinitely large and the exciting current is of uniform distribution. The measurement on the steel plate shows that this method has high spatial resolution. Then, we extended this methodology to a toroidal geometry with the objective of determining the poloidal distribution of the toroidal component of the eddy current density associated with plasma disruption in a fusion reactor called J-TEXT. The preliminary measured result is consistent with the analysis and calculation results on the J-TEXT vacuum vessel. PMID- 26827317 TI - Development of real-time rotating waveplate Stokes polarimeter using multi-order retardation for ITER poloidal polarimeter. AB - The rotating waveplate Stokes polarimeter was developed for ITER (International Thermonuclear Experimental Reactor) poloidal polarimeter. The generalized model of the rotating waveplate Stokes polarimeter and the algorithm suitable for real time field-programmable gate array (FPGA) processing were proposed. Since the generalized model takes into account each component associated with the rotation of the waveplate, the Stokes parameters can be accurately measured even in unideal condition such as non-uniformity of the waveplate retardation. Experiments using a He-Ne laser showed that the maximum error and the precision of the Stokes parameter were 3.5% and 1.2%, respectively. The rotation speed of waveplate was 20 000 rpm and time resolution of measuring the Stokes parameter was 3.3 ms. Software emulation showed that the real-time measurement of the Stokes parameter with time resolution of less than 10 ms is possible by using several FPGA boards. Evaluation of measurement capability using a far-infrared laser which ITER poloidal polarimeter will use concluded that measurement error will be reduced by a factor of nine. PMID- 26827318 TI - Image computing techniques to extrapolate data for dust tracking in case of an experimental accident simulation in a nuclear fusion plant. AB - In this paper, a preliminary shadowgraph-based analysis of dust particles re suspension due to loss of vacuum accident (LOVA) in ITER-like nuclear fusion reactors has been presented. Dust particles are produced through different mechanisms in nuclear fusion devices, one of the main issues is that dust particles are capable of being re-suspended in case of events such as LOVA. Shadowgraph is based on an expanded collimated beam of light emitted by a laser or a lamp that emits light transversely compared to the flow field direction. In the STARDUST facility, the dust moves in the flow, and it causes variations of refractive index that can be detected by using a CCD camera. The STARDUST fast camera setup allows to detect and to track dust particles moving in the vessel and then to obtain information about the velocity field of dust mobilized. In particular, the acquired images are processed such that per each frame the moving dust particles are detected by applying a background subtraction technique based on the mixture of Gaussian algorithm. The obtained foreground masks are eventually filtered with morphological operations. Finally, a multi-object tracking algorithm is used to track the detected particles along the experiment. For each particle, a Kalman filter-based tracker is applied; the particles dynamic is described by taking into account position, velocity, and acceleration as state variable. The results demonstrate that it is possible to obtain dust particles' velocity field during LOVA by automatically processing the data obtained with the shadowgraph approach. PMID- 26827319 TI - A novel laser-induced fluorescence scheme for Ar-I in a plasma. AB - Here we describe a novel infrared laser-induced fluorescence scheme for the 1s2 state of Ar-I using an 841.052 nm (vacuum) Sacher tunable diode laser oscillator and compare it to an established 667.913 nm (vacuum) 1s4-pumping Ar-I LIF scheme using a master oscillator power amplifier laser [A. M. Keesee et al. Rev. Sci. Instrum. 75, 4091 (2004)]. The novel scheme exhibits a significantly greater signal-to-noise ratio for a given injected laser power than the established scheme. We argue that this is caused by less intense spontaneous Ar-I radiation near the LIF emission wavelength for the 1s2 scheme as compared to the 1s4 scheme. In addition we present an updated iodine cell spectrum around the 1s4 LIF scheme pump wavelength. PMID- 26827320 TI - Post calibration of the two-dimensional electron cyclotron emission imaging instrument with electron temperature characteristics of the magnetohydrodynamic instabilities. AB - The electron cyclotron emission imaging (ECEI) instrument is widely used to study the local electron temperature (Te) fluctuations by measuring the ECE intensity IECE ? Te in tokamak plasmas. The ECEI measurement is often processed in a normalized fluctuation quantity against the time averaged value due to complication in absolute calibration. In this paper, the ECEI channels are relatively calibrated using the flat Te assumption of the sawtooth crash or the tearing mode island and a proper extrapolation. The 2-D relatively calibrated electron temperature (Te,rel) images are reconstructed and the displacement amplitude of the magnetohydrodynamic modes can be measured for the accurate quantitative growth analysis. PMID- 26827321 TI - Edge profile analysis of Joint European Torus (JET) Thomson scattering data: Quantifying the systematic error due to edge localised mode synchronisation. AB - The Joint European Torus (JET) high resolution Thomson scattering (HRTS) system measures radial electron temperature and density profiles. One of the key capabilities of this diagnostic is measuring the steep pressure gradient, termed the pedestal, at the edge of JET plasmas. The pedestal is susceptible to limiting instabilities, such as Edge Localised Modes (ELMs), characterised by a periodic collapse of the steep gradient region. A common method to extract the pedestal width, gradient, and height, used on numerous machines, is by performing a modified hyperbolic tangent (mtanh) fit to overlaid profiles selected from the same region of the ELM cycle. This process of overlaying profiles, termed ELM synchronisation, maximises the number of data points defining the pedestal region for a given phase of the ELM cycle. When fitting to HRTS profiles, it is necessary to incorporate the diagnostic radial instrument function, particularly important when considering the pedestal width. A deconvolved fit is determined by a forward convolution method requiring knowledge of only the instrument function and profiles. The systematic error due to the deconvolution technique incorporated into the JET pedestal fitting tool has been documented by Frassinetti et al. [Rev. Sci. Instrum. 83, 013506 (2012)]. This paper seeks to understand and quantify the systematic error introduced to the pedestal width due to ELM synchronisation. Synthetic profiles, generated with error bars and point to-point variation characteristic of real HRTS profiles, are used to evaluate the deviation from the underlying pedestal width. We find on JET that the ELM synchronisation systematic error is negligible in comparison to the statistical error when assuming ten overlaid profiles (typical for a pre-ELM fit to HRTS profiles). This confirms that fitting a mtanh to ELM synchronised profiles is a robust and practical technique for extracting the pedestal structure. PMID- 26827322 TI - Region-of-interest diffuse optical tomography system. AB - Diffuse optical tomography (DOT) using near-infrared light is a promising tool for non-invasive imaging of deep tissue. This technique is capable of quantitative reconstruction of absorption (MUa) and scattering coefficient (MUs) inhomogeneities in the tissue. The rationale for reconstructing the optical property map is that the absorption coefficient variation provides diagnostic information about metabolic and disease states of the tissue. The aim of DOT is to reconstruct the internal tissue cross section with good spatial resolution and contrast from noisy measurements non-invasively. We develop a region-of-interest scanning system based on DOT principles. Modulated light is injected into the phantom/tissue through one of the four light emitting diode sources. The light traversing through the tissue gets partially absorbed and scattered multiple times. The intensity and phase of the exiting light are measured using a set of photodetectors. The light transport through a tissue is diffusive in nature and is modeled using radiative transfer equation. However, a simplified model based on diffusion equation (DE) can be used if the system satisfies following conditions: (a) the optical parameter of the inhomogeneity is close to the optical property of the background, and (b) MUs of the medium is much greater than MUa (MUs > > MUa). The light transport through a highly scattering tissue satisfies both of these conditions. A discrete version of DE based on finite element method is used for solving the inverse problem. The depth of probing light inside the tissue depends on the wavelength of light, absorption, and scattering coefficients of the medium and the separation between the source and detector locations. Extensive simulation studies have been carried out and the results are validated using two sets of experimental measurements. The utility of the system can be further improved by using multiple wavelength light sources. In such a scheme, the spectroscopic variation of absorption coefficient in the tissue can be used to arrive at the oxygenation changes in the tissue. PMID- 26827323 TI - Calibration procedures for quantitative multiple wavelengths reflectance microscopy. AB - In order to characterize surface chemo-mechanical phenomena driving micro-electro mechanical systems (MEMSs) behavior, it has been previously proposed to use reflected intensity fields obtained from a standard microscope for different illumination wavelengths. Wavelength-dependent and -independent reflectivity fields are obtained from these images, provided the relative reflectance sensitivities ratio can be identified. This contribution focuses on the necessary calibration procedures and mathematical methods allowing for a quantitative conversion from a mechanically induced reflectivity field to a surface rotation field, therefore paving the way for a quantitative mechanical analysis of MEMS under chemical loading. PMID- 26827324 TI - Characterizing nanoscale scanning probes using electron microscopy: A novel fixture and a practical guide. AB - The nanoscale geometry of probe tips used for atomic force microscopy (AFM) measurements determines the lateral resolution, contributes to the strength of the tip-surface interaction, and can be a significant source of uncertainty in the quantitative analysis of results. While inverse imaging of the probe tip has been used successfully to determine probe tip geometry, direct observation of the tip profile using electron microscopy (EM) confers several advantages: it provides direct (rather than indirect) imaging, requires fewer algorithmic parameters, and does not require bringing the tip into contact with a sample. In the past, EM-based observation of the probe tip has been achieved using ad hoc mounting methods that are constrained by low throughput, the risk of contamination, and repeatability issues. We report on a probe fixture designed for use in a commercial transmission electron microscope that enables repeatable mounting of multiple AFM probes as well as a reference grid for beam alignment. This communication describes the design, fabrication, and advantages of this probe fixture, including full technical drawings for machining. Further, best practices are discussed for repeatable, non-destructive probe imaging. Finally, examples of the fixture's use are described, including characterization of common commercial AFM probes in their out-of-the-box condition. PMID- 26827325 TI - Design and performance of a compact scanning transmission X-ray microscope at the Photon Factory. AB - We present a new compact instrument designed for scanning transmission X-ray microscopy. It has piezo-driven linear stages, making it small and light. Optical components from the virtual source point to the detector are located on a single optical table, resulting in a portable instrument that can be operated at a general-purpose spectroscopy beamline without requiring any major reconstruction. Careful consideration has been given to solving the vibration problem common to high-resolution microscopy, so as not to affect the spatial resolution determined by the Fresnel zone plate. Results on bacteriogenic iron oxides, single particle aerosols, and rare-earth permanent magnets are presented as examples of its performance under diverse applications. PMID- 26827327 TI - In situ surface/interface x-ray diffractometer for oxide molecular beam epitaxy. AB - In situ studies of oxide molecular beam epitaxy by synchrotron x-ray scattering has been made possible by upgrading an existing UHV/molecular beam epitaxy (MBE) six-circle diffractometer system. For oxide MBE growth, pure ozone delivery to the chamber has been made available, and several new deposition sources have been made available on a new 12 in. CF (ConFlat, a registered trademark of Varian, Inc.) flange. X-ray diffraction has been used as a major probe for film growth and structures for the system. In the original design, electron diffraction was intended for the secondary diagnostics available without the necessity of the x ray and located at separate positions. Deposition of films was made possible at the two diagnostic positions. And, the aiming of the evaporation sources is fixed to the point between two locations. Ozone can be supplied through two separate nozzles for each location. Also two separate thickness monitors are installed. Additional features of the equipment are also presented together with the data taken during typical oxide film growth to illustrate the depth of information available via in situ x-ray techniques. PMID- 26827326 TI - High performance dual-mode surface plasmon coupled emission imaging apparatus integrating Kretschmann and reverse Kretschmann configurations for flexible measurements. AB - A Kretschmann (KR) and reverse Kretschmann (RK) dual-mode surface plasmon coupled emission (SPCE) imaging apparatus based on prism coupling was built up. Highly directional and polarized fluorescence images for both RK and KR configurations were obtained. Besides, surface plasmon field-enhanced fluorescence and free space imaging can also be measured conveniently from this apparatus. Combining the high sensitivity of KR mode and the simplicity of RK mode, the multifunctional imaging system is flexible to provide different configurations for imaging applications. Compared to the free space imaging, SPCE imaging provides enhanced fluorescence, especially large enhancement up to about 50 fold in KR configuration. Additionally, the degree of evanescent field enhancement effect was easily estimated experimentally using the apparatus to compare the different imaging configurations. We believed that the dual-mode SPCE imaging apparatus will be useful in fundamental study of plasmon-controlled fluorescence and be a powerful tool for optical imaging, especially for microarray and biological applications. PMID- 26827328 TI - New method of plasma immersion ion implantation and also deposition of industrial components using tubular fixture and plasma generated inside the tube by high voltage pulses. AB - A new method of Plasma Immersion Ion Implantation (PIII) and deposition (PIII and D) for treating industrial components in the batch mode has been developed. A metal tubular fixture is used to allocate the components inside, around, and along the tube, exposing only the parts of each component that are to be ion implanted to the plasma. Hollow cathode-like plasma is generated only inside the tube filled with the desired gas, by applying high negative voltage pulses to the hollow cylindrical fixture which is insulated from the vacuum chamber walls. This is a very convenient method of batch processing of industrial parts by ion implantation, in which a large number of small to medium sized components can be treated by PIII and PIII and D, very quickly, efficiently, and also at low cost. PMID- 26827329 TI - A new setup for the investigation of swift heavy ion induced particle emission and surface modifications. AB - The irradiation with fast ions with kinetic energies of >10 MeV leads to the deposition of a high amount of energy along their trajectory (up to several ten keV/nm). The energy is mainly transferred to the electronic subsystem and induces different secondary processes of excitations, which result in significant material modifications. A new setup to study these ion induced effects on surfaces will be described in this paper. The setup combines a variable irradiation chamber with different techniques of surface characterizations like scanning probe microscopy, time-of-flight secondary ion, and neutral mass spectrometry, as well as low energy electron diffraction under ultra high vacuum conditions, and is mounted at a beamline of the universal linear accelerator (UNILAC) of the GSI facility in Darmstadt, Germany. Here, samples can be irradiated with high-energy ions with a total kinetic energy up to several GeVs under different angles of incidence. Our setup enables the preparation and in situ analysis of different types of sample systems ranging from metals to insulators. Time-of-flight secondary ion mass spectrometry enables us to study the chemical composition of the surface, while scanning probe microscopy allows a detailed view into the local electrical and morphological conditions of the sample surface down to atomic scales. With the new setup, particle emission during irradiation as well as persistent modifications of the surface after irradiation can thus be studied. We present first data obtained with the new setup, including a novel measuring protocol for time-of-flight mass spectrometry with the GSI UNILAC accelerator. PMID- 26827330 TI - Electrostatic levitation facility optimized for neutron diffraction studies of high temperature liquids at a spallation neutron source. AB - Neutron diffraction studies of metallic liquids provide valuable information about inherent topological and chemical ordering on multiple length scales as well as insight into dynamical processes at the level of a few atoms. However, there exist very few facilities in the world that allow such studies to be made of reactive metallic liquids in a containerless environment, and these are designed for use at reactor-based neutron sources. We present an electrostatic levitation facility, NESL (for Neutron ElectroStatic Levitator), which takes advantage of the enhanced capabilities and increased neutron flux available at spallation neutron sources (SNSs). NESL enables high quality elastic and inelastic neutron scattering experiments to be made of reactive metallic and other liquids in the equilibrium and supercooled temperature regime. The apparatus is comprised of a high vacuum chamber, external and internal neutron collimation optics, and a sample exchange mechanism that allows up to 30 samples to be processed between chamber openings. Two heating lasers allow excellent sample temperature homogeneity, even for samples approaching 500 mg, and an automated temperature control system allows isothermal measurements to be conducted for times approaching 2 h in the liquid state, with variations in the average sample temperature of less than 0.5%. To demonstrate the capabilities of the facility for elastic scattering studies of liquids, a high quality total structure factor for Zr64Ni36 measured slightly above the liquidus temperature is presented from experiments conducted on the nanoscale-ordered materials diffractometer (NOMAD) beam line at the SNS after only 30 min of acquisition time for a small sample (~100 mg). PMID- 26827331 TI - An optically accessible pyrolysis microreactor. AB - We report an optically accessible pyrolysis micro-reactor suitable for in situ laser spectroscopic measurements. A radiative heating design allows for completely unobstructed views of the micro-reactor along two axes. The maximum temperature demonstrated here is only 1300 K (as opposed to 1700 K for the usual SiC micro-reactor) because of the melting point of fused silica, but alternative transparent materials will allow for higher temperatures. Laser induced fluorescence measurements on nitric oxide are presented as a proof of principle for spectroscopic characterization of pyrolysis conditions. PMID- 26827332 TI - A thin permeable-membrane device for single-molecule manipulation. AB - Single-molecule manipulation instruments have unparalleled abilities to interrogate the structure and elasticity of single biomolecules. Key insights are derived by measuring the system response in varying solution conditions; yet, typical solution control strategies require imposing a direct fluid flow on the measured biomolecule that perturbs the high-sensitivity measurement and/or removes interacting molecules by advection. An alternate approach is to fabricate devices that permit solution changes by diffusion of the introduced species through permeable membranes, rather than by direct solution flow through the sensing region. Prior implementations of permeable-membrane devices are relatively thick, disallowing their use in apparatus that require the simultaneous close approach of external instrumentation from two sides, as occurs in single-molecule manipulation devices like the magnetic tweezer. Here, we describe the construction and use of a thin microfluidic device appropriate for single-molecule studies. We create a flow cell of only ~500 MUm total thickness by sandwiching glass coverslips around a thin plastic gasket and then create permeable walls between laterally separated channels in situ through photo induced cross-linking of poly(ethylene glycol) diacrylate hydrogels. We show that these membranes permit passage of ions and small molecules (thus permitting solution equilibration in the absence of direct flow), but the membranes block the passage of larger biomolecules (thus retaining precious samples). Finally, we demonstrate the suitability of the device for high-resolution magnetic-tweezer experiments by measuring the salt-dependent folding of a single RNA hairpin under force. PMID- 26827333 TI - A cryogenic rotation stage with a large clear aperture for the half-wave plates in the Spider instrument. AB - We describe the cryogenic half-wave plate rotation mechanisms built for and used in Spider, a polarization-sensitive balloon-borne telescope array that observed the cosmic microwave background at 95 GHz and 150 GHz during a stratospheric balloon flight from Antarctica in January 2015. The mechanisms operate at liquid helium temperature in flight. A three-point contact design keeps the mechanical bearings relatively small but allows for a large (305 mm) diameter clear aperture. A worm gear driven by a cryogenic stepper motor allows for precise positioning and prevents undesired rotation when the motors are depowered. A custom-built optical encoder system monitors the bearing angle to an absolute accuracy of +/-0.1(?). The system performed well in Spider during its successful 16 day flight. PMID- 26827335 TI - An FPGA-based instrumentation platform for use at deep cryogenic temperatures. AB - We describe the operation of a cryogenic instrumentation platform incorporating commercially available field-programmable gate arrays (FPGAs). The functionality of the FPGAs at temperatures approaching 4 K enables signal routing, multiplexing, and complex digital signal processing in close proximity to cooled devices or detectors within the cryostat. The performance of the FPGAs in a cryogenic environment is evaluated, including clock speed, error rates, and power consumption. Although constructed for the purpose of controlling and reading out quantum computing devices with low latency, the instrument is generic enough to be of broad use in a range of cryogenic applications. PMID- 26827336 TI - Terahertz antenna electronic chopper. AB - In this paper, we present an electronic circuit used to bias a photoconductive antenna that generates terahertz radiation. The working principles and the design process for the device are discussed in detail. The noise and shape of the wave measurements for a built device are considered. Furthermore, their impact on a terahertz pulse and its spectra is also examined. The proposed implementation is simple to build, robust and offers a real improvement over THz instrumentation due to the frequency tuning. Additionally, it provides for galvanic isolation and ESD protection. PMID- 26827334 TI - The advanced LIGO input optics. AB - The advanced LIGO gravitational wave detectors are nearing their design sensitivity and should begin taking meaningful astrophysical data in the fall of 2015. These resonant optical interferometers will have unprecedented sensitivity to the strains caused by passing gravitational waves. The input optics play a significant part in allowing these devices to reach such sensitivities. Residing between the pre-stabilized laser and the main interferometer, the input optics subsystem is tasked with preparing the laser beam for interferometry at the sub attometer level while operating at continuous wave input power levels ranging from 100 mW to 150 W. These extreme operating conditions required every major component to be custom designed. These designs draw heavily on the experience and understanding gained during the operation of Initial LIGO and Enhanced LIGO. In this article, we report on how the components of the input optics were designed to meet their stringent requirements and present measurements showing how well they have lived up to their design. PMID- 26827337 TI - Design of the 1.5 MW, 30-96 MHz ultra-wideband 3 dB high power hybrid coupler for Ion Cyclotron Resonance Frequency (ICRF) heating in fusion grade reactor. AB - Design and developmental procedure of strip-line based 1.5 MW, 30-96 MHz, ultra wideband high power 3 dB hybrid coupler has been presented and its applicability in ion cyclotron resonance heating (ICRH) in tokamak is discussed. For the high power handling capability, spacing between conductors and ground need to very high. Hence other structural parameters like strip-width, strip thickness coupling gap, and junction also become large which can be gone upto optimum limit where various constrains like fabrication tolerance, discontinuities, and excitation of higher TE and TM modes become prominent and significantly deteriorates the desired parameters of the coupled lines system. In designed hybrid coupler, two 8.34 dB coupled lines are connected in tandem to get desired coupling of 3 dB and air is used as dielectric. The spacing between ground and conductors are taken as 0.164 m for 1.5 MW power handling capability. To have the desired spacing, each of 8.34 dB segments are designed with inner dimension of 3.6 * 1.0 * 40 cm where constraints have been significantly realized, compensated, and applied in designing of 1.5 MW hybrid coupler and presented in paper. PMID- 26827338 TI - Sub-terahertz microsecond optically controlled switch with GaAs active element beyond the photoelectric threshold. AB - We study an unusual working regime of a recently developed sub-terahertz microwave cavity-based switch. The resonator cavity includes a semiconductor plate which is illuminated by laser emission beyond the photoelectric threshold. Despite a significant change to the conventional process of photoelectric effect we have found that the switch works. Typical switching performance rate is about 1 MUs for the regime. A process of carrier density relaxation beyond the photoelectric threshold is discussed. An idea of diagnostic method for the semiconductor's quality is proposed. PMID- 26827339 TI - An instrument for charge measurement due to a single collision between two spherical particles. AB - It universally exists in moving particular systems that particles can be electrified, in which the particles are chemically identical, just as toner particles, coal dust, and pharmaceutical powders. However, owing to the limit of experimental instruments, so far, there are yet no experiments to illustrate whether a particle can be electrified due to a single collision between two spherical particles, and there are also no experiments to measure the charge carried by a single particle due to a single collision between two particles. So we have developed an instrument for charge measurement due to a single collision between two spheres. The instrument consists of two-sphere collision device, collision charge measurement apparatus, and particles' trajectory tracking system. By using this instrument, we can investigate the collision contact electrification due to a single collision between two spheres and simultaneously record the moving trajectories of spheres after the collision to calculate the rebound angles to identify the contribution of the triboelectrification due to the rubbing between the contact surfaces and the collision contact electrification due to the normal pressure between the contact surfaces. PMID- 26827340 TI - Performance evaluation of a lossy transmission lines based diode detector at cryogenic temperature. AB - This work is focused on the design, fabrication, and performance analysis of a square-law Schottky diode detector based on lossy transmission lines working under cryogenic temperature (15 K). The design analysis of a microwave detector, based on a planar gallium-arsenide low effective Schottky barrier height diode, is reported, which is aimed for achieving large input return loss as well as flat sensitivity versus frequency. The designed circuit demonstrates good sensitivity, as well as a good return loss in a wide bandwidth at Ka-band, at both room (300 K) and cryogenic (15 K) temperatures. A good sensitivity of 1000 mV/mW and input return loss better than 12 dB have been achieved when it works as a zero-bias Schottky diode detector at room temperature, increasing the sensitivity up to a minimum of 2200 mV/mW, with the need of a DC bias current, at cryogenic temperature. PMID- 26827341 TI - In situ tuning of coupled superconducting microwave resonators. AB - In order to transfer a range of important optical experiments into the microwave regime, a pair of near-identical, weakly coupled resonators is required. We describe a simple tuning mechanism for taking a pair of coupled, coplanar resonators through the avoided crossing in a controlled way. We see no obvious degradation of their high quality factor and find very good agreement with theoretical expectations. PMID- 26827342 TI - Uncertainty analysis of thermoreflectance measurements. AB - We derive a generally applicable formula to calculate the precision of multi parameter measurements that apply least squares algorithms. This formula, which accounts for experimental noise and uncertainty in the controlled model parameters, is then used to analyze the uncertainty of thermal property measurements with pump-probe thermoreflectance techniques. We compare the uncertainty of time domain thermoreflectance and frequency domain thermoreflectance (FDTR) when measuring bulk materials and thin films, considering simultaneous measurements of various combinations of thermal properties, including thermal conductivity, heat capacity, and thermal boundary conductance. We validate the uncertainty analysis using Monte Carlo simulations on data from FDTR measurements of an 80 nm gold film on fused silica. PMID- 26827343 TI - Acoustically enhanced heat transport. AB - We investigate the enhancement of heat transfer in the nucleate boiling regime by inducing high frequency acoustic waves (f ~ 10(6) Hz) on the heated surface. In the experiments, liquid droplets (deionized water) are dispensed directly onto a heated, vibrating substrate. At lower vibration amplitudes (xis ~ 10(-9) m), the improved heat transfer is mainly due to the detachment of vapor bubbles from the heated surface and the induced thermal mixing. Upon increasing the vibration amplitude (xis ~ 10(-8) m), the heat transfer becomes more substantial due to the rapid bursting of vapor bubbles happening at the liquid-air interface as a consequence of capillary waves travelling in the thin liquid film between the vapor bubble and the air. Further increases then lead to rapid atomization that continues to enhance the heat transfer. An acoustic wave displacement amplitude on the order of 10(-8) m with 10(6) Hz order frequencies is observed to produce an improvement of up to 50% reduction in the surface temperature over the case without acoustic excitation. PMID- 26827344 TI - A step-wise steerable source of illumination for low-noise "Violin-Mode" shadow sensors, intended for use in interferometric gravitational wave detectors. AB - A steerable low-noise source of illumination is described for shadow-sensors having a displacement sensitivity of ~100 pm (rms)/?Hz, at 500 Hz, over a measuring span of at least +/-0.5 mm. These sensors were designed to detect lateral "Violin-Mode" resonances in the highly tensioned fused-silica suspension fibres of the test-masses/mirrors for the Advanced Laser Interferometer Gravitational Wave Observatory gravitational wave detectors. The shadow sensors one intended for each of the four fibres in a suspension-comprised a source of Near InfraRed (NIR) radiation (emitter) and a differential shadow-displacement sensor (detector), these bracketing the fibre under test. The suspension fibres themselves were approximately 600 mm long by 0.4 mm in diameter, and when illuminated from the side, they cast narrow, vertical, shadows onto their respective detectors-these being located at an effective distance of 50 fibre diameters behind the axes of the fibres themselves. The emitter described here was designed to compensate for a significant degree of mechanical drift or creep over time in the mean position of its suspension fibre. This was achieved by employing five adjacent columns of 8 * miniature NIR LEDs (Light Emitting Diodes, lambda = 890 nm), with one column being activated at a time. When used in conjunction with a "reverse Galilean" telescope, the LED sources allowed the collimated beam from the emitter to be steered azimuthally in fine angular increments (0.65 degrees ), causing the fibre's shadow to move laterally, in a step-wise manner, across the plane of its facing detector. Each step in shadow position was approximately 0.23 mm in size, and this allowed the fibre's shadow to be re-centred, so as to bridge once again both elements of its photodiode detector-even if the fibre was off-centred by as much as +/-0.5 mm. Re-centring allowed Violin-Mode vibrations of the fibre to be sensed once again as differential AC photocurrents, these flowing in anti-phase in the two elements of the "split-photodiode" detector. PMID- 26827345 TI - A generic "micro-Stoney" method for the measurement of internal stress and elastic modulus of ultrathin films. AB - Accurate measurement of the mechanical properties of ultra-thin films with thicknesses typically below 100 nm is a challenging issue with an interest in many fields involving coating technologies, microelectronics, and MEMS. A bilayer curvature based method is developed for the simultaneous determination of the elastic mismatch strain and Young's modulus of ultra-thin films. The idea is to deposit the film or coating on very thin cantilevers in order to amplify the curvature compared to a traditional "Stoney" wafer curvature test, hence the terminology "micro-Stoney." The data reduction is based on the comparison of the curvatures obtained for different supporting layer thicknesses. The elastic mismatch strain and Young's modulus are obtained from curvature measurements of cantilevers before and after the film deposition. The data reduction scheme relies on both analytical and finite element calculations, depending on the magnitude of the curvature. The experimental validation has been performed on ultra-thin low pressure chemical vapor deposited silicon nitride films with thickness ranging between 54 and 133 nm deposited on silicon cantilevers. The technique is sensitive to the cantilever geometry, in particular, to the thickness ratio and width/thickness ratio. Therefore, the precision in the determination of the latter quantities determines the accuracy on the extracted elastic mismatch strain and elastic modulus. The method can be potentially applied to films as thin as a few nanometers. PMID- 26827346 TI - Three-dimensional piezoelectric vibration energy harvester using spiral-shaped beam with triple operating frequencies. AB - This work has demonstrated a novel piezoelectric energy harvester without a complex structure and appended component that is capable of scavenging vibration energy from arbitrary directions with multiple resonant frequencies. In this harvester, a spiral-shaped elastic thin beam instead of a traditional thin cantilever beam was adopted to absorb external vibration with arbitrary direction in three-dimensional (3D) spaces owing to its ability to bend flexibly and stretch along arbitrary direction. Furthermore, multiple modes in the elastic thin beam contribute to a possibility to widen the working bandwidth with multiple resonant frequencies. The experimental results show that the harvester was capable of scavenging the vibration energy in 3D arbitrary directions; they also exhibited triple power peaks at about 16 Hz, 21 Hz, and 28 Hz with the powers of 330 MUW, 313 MUW, and 6 MUW, respectively. In addition, human walking and water wave energies were successfully converted into electricity, proving that our harvester was practical to scavenge the time-variant or multi directional vibration energies in our daily life. PMID- 26827347 TI - Controlling system components with a sound card: A versatile inkjet fluid testing platform. AB - In this paper, we demonstrate how to use a personal computer sound card to develop an experimental platform for evaluating the jettability and jetting behavior of inkjet fluids. The test fluid is driven out of a nozzle acoustically using a loudspeaker, forming a jet. The subsequent jet breakup process is then captured using a stroboscopic light source and a camera. Instead of using a delay generator as in previous work, the current setup uses a computer sound card and audio amplifier to (i) generate actuation waveforms of arbitrary shapes and (ii) synchronize the jet actuation and imaging with a time precision close to 5 MUs. To correct for any signal distortions caused by the built-in high pass filters of the sound card and amplifier, a numerical filter is created and applied before sending the desired signal to the sound card. Such correction method does not require physically modifying the hardware of the sound card or amplifier and is applicable to different waveforms and filters provided that the transfer function is correctly identified. The platform has been tested using 20% (v/v) glycerol in water as a model fluid. Combining this platform with digital image analysis further enables a quantitative assessment of parameters such as the volumes and positions of the jet and drop that are important for quality control and development of new ink formulations. PMID- 26827348 TI - Development of a precision reverse offset printing system. AB - In printed electronics technology, the overlay accuracy of printed patterns is a very important issue when applying printing technology to the production of electric devices. In order to achieve accurate positioning of the printed patterns, this study proposes a novel precision reverse offset printing system. Furthermore, the study evaluates the effects of synchronization and printing force on position errors of the printed patterns, and presents methods of controlling synchronization and printing force so as to eliminate positional errors caused by the above-mentioned reasons. Finally, the printing position repeatability of 0.40 MUm and 0.32 MUm (x and y direction, respectively) at a sigma level is obtained over the dimension of 100 mm under repeated printing tests with identical printing conditions. PMID- 26827349 TI - Spherical fused silica cells filled with pure helium for nuclear magnetic resonance-magnetometry. AB - High magnetic fields (>1 T) are measured by NMR magnetometers with unrivaled precision if the precessing spin sample provides long coherence times. The longest coherence times are found in diluted (3)He samples, which can be hyperpolarized for sufficient signal strength. In order to have minimal influence on the homogeneity and value of the measured magnetic field, the optimal container for the (3)He should be a perfect sphere. A fused silica sphere with an inner diameter of 8 mm and an outer diameter of 12 mm was made from two hemispheres by diffusion bonding leaving only a small hole for cleaning and evacuation. This hole was closed in vacuum by a CO2 laser and the inner volume was filled with a few mbars of (3)He via wall permeation. NMR-measurements on such a sample had coherence times of 5 min. While the hemispheres were produced with <1 MUm deviation from sphericity, the bonding left a step of ca. 50 MUm at maximum. The influence of such a mismatch, its orientation, and the immediate environment of the sample is analyzed by FEM-simulations and discussed in view of coherence times and absolute field measurements. PMID- 26827350 TI - Development and numerical/experimental characterization of a lab-scale flat flame reactor allowing the analysis of pulverized solid fuel devolatilization and oxidation at high heating rates. AB - This paper deals with the thorough characterization of a new experimental test bench designed to study the devolatilization and oxidation of pulverized fuel particles in a wide range of operating conditions. This lab-scale facility is composed of a fuel feeding system, the functioning of which has been optimized by computational fluid dynamics. It allows delivering a constant and time independent mass flow rate of fuel particles which are pneumatically transported to the central injector of a hybrid McKenna burner using a carrier gas stream that can be inert or oxidant depending on the targeted application. A premixed propane/air laminar flat flame stabilized on the porous part of the burner is used to generate the hot gases insuring the heating of the central coal/carrier gas jet with a thermal gradient similar to those found in industrial combustors (>10(5) K/s). In the present work, results issued from numerical simulations performed a priori to characterize the velocity and temperature fields in the reaction chamber have been analyzed and confronted with experimental measurements carried out by coupling particle image velocimetry, thermocouple and two-color pyrometry measurements so as to validate the order of magnitude of the heating rate delivered by such a new test bench. Finally, the main features of the flat flame reactor we developed have been discussed with respect to those of another laboratory-scale system designed to study coal devolatilization at a high heating rate. PMID- 26827351 TI - Apparatus for the measurement of electrical resistivity, Seebeck coefficient, and thermal conductivity of thermoelectric materials between 300 K and 12 K. AB - We have developed a custom apparatus for the consecutive measurement of the electrical resistivity, the Seebeck coefficient, and the thermal conductivity of materials between 300 K and 12 K. These three transport properties provide for a basic understanding of the thermal and electrical properties of materials. They are of fundamental importance in identifying and optimizing new materials for thermoelectric applications. Thermoelectric applications include waste heat recovery for automobile engines and industrial power generators, solid-state refrigeration, and remote power generation for sensors and space probes. The electrical resistivity is measured using a four-probe bipolar technique, the Seebeck coefficient is measured using the quasi-steady-state condition of the differential method in a 2-probe arrangement, and the thermal conductivity is measured using a longitudinal, multiple gradient steady-state technique. We describe the instrumentation and the measurement uncertainty associated with each transport property, each of which is presented with representative measurement comparisons using round robin samples and/or certified reference materials. Transport properties data from this apparatus have supported the identification, development, and phenomenological understanding of novel thermoelectric materials. PMID- 26827352 TI - In situ multi-modal monitoring of solvent vapor swelling in polymer thin films. AB - Polymer processing techniques involving solvent vapor swelling are typically challenging to control and thus reproduce. Moreover, traditional descriptions of solvent swollen films lack microscopic detail. We describe the design and use of an apparatus that facilitates macroscopic and microscopic characterization of samples undergoing solvent vapor swelling in a controlled environment. The experimental design incorporates three critical characteristics: (1) a mass-flow controlled solvent vapor delivery system allows for precise control of the amount of solvent vapor delivered to the sample, (2) a sample prepared on a quartz crystal microbalance allows for real-time assessment of the extent of sample swelling, (3) a second sample prepared and assessed in parallel on a coverslip allows real-time fluorescence microscopy during swelling. We demonstrate that this apparatus allows for single-particle tracking, which in turn facilitates in situ monitoring of local environments within the solvent-swollen film. PMID- 26827353 TI - Energy transfer model and its applications of ultrasonic gas flow-meter under static and dynamic flow rates. AB - Most of the ultrasonic gas flow-meters measure the gas flow rate by calculating the ultrasonic transmission time difference between the downstream and upstream. Ultrasonic energy attenuation occurs in the processes of the ultrasonic generation, conversion, transmission, and reception. Additionally, at the same time, the gas flow will also affect the ultrasonic propagation during the measurement, which results in the ultrasonic energy attenuation and the offset of ultrasonic propagation path. Thus, the ultrasonic energy received by the transducer is weaker. When the gas flow rate increases, this effect becomes more apparent. It leads to the measurement accuracy reduced, and the measurement range narrowed. An energy transfer model, where the ultrasonic gas flow-meter under without/with the gas flow, is established by adopting the statistical analysis and curve fitting based on a large amount of experimental data. The static sub model without the gas flow expresses the energy conversion efficiency of ultrasonic gas transducers, and the dynamic sub model with the gas flow reflects the energy attenuation pattern following the flow rate variations. The mathematical model can be used to determine the minimum energy of the excitation signal for meeting the requirement of specific measurement range, and predict the maximum measurable flow rate in the case of fixed energy of excitation signal. Based on the above studies, a method to enhance the excitation signal energy is proposed under the output power of the transmitting circuit being a finite value so as to extend the measurement rage of ultrasonic gas flow-meter. PMID- 26827354 TI - Early-stage fault isolation based on frequency response fitted by small-size samples for cryogenic cold compressors with active magnetic bearings. AB - A model-based method for fault detection and early-stage isolation, applicable when unfaulty conditions can be identified only by a reduced number of trials (even only one), is presented. The basic idea is to model analytically the uncertainty of the unfaulty frequency response and express the fault condition in terms of the noise power variance. A preliminary fault isolation is carried out by sensitivity analysis in order to identify the most influencing model parameters and assess their influence on the estimated noise. Then, during maintenance tests, the noise power is checked to detect the faulty condition. This technique is conceived to check the quality of a critical component in an experimental installation (fault detection and early-stage isolation), as well as to detect its faulty dynamic behaviors over a long horizon maintenance test campaign (condition monitoring). The method was applied to four cold compressors with active magnetic bearings at CERN by proving to be able to detect an actual faulty condition in one of such compressors. PMID- 26827355 TI - Development of the experimental procedure to examine the response of carbon fiber reinforced polymer composites subjected to a high-intensity pulsed electric field and low-velocity impact. AB - A new fully automated experimental setup has been developed to study the response of carbon fiber reinforced polymer (CFRP) composites subjected to a high intensity pulsed electric field and low-velocity impact. The experimental setup allows for real-time measurements of the pulsed electric current, voltage, impact load, and displacements on the CFRP composite specimens. The setup includes a new custom-built current pulse generator that utilizes a bank of capacitor modules capable of producing a 20 ms current pulse with an amplitude of up to 2500 A. The setup enabled application of the pulsed current and impact load and successfully achieved coordination between the peak of the current pulse and the peak of the impact load. A series of electrical, impact, and coordinated electrical-impact characterization tests were performed on 32-ply IM7/977-3 unidirectional CFRP composites to assess their ability to withstand application of a pulsed electric current and determine the effects of the pulsed current on the impact response. Experimental results revealed that the electrical resistance of CFRP composites decreased with an increase in the electric current magnitude. It was also found that the electrified CFRP specimens withstood higher average impact loads compared to the non-electrified specimens. PMID- 26827356 TI - High order magnetic optics for high dynamic range proton radiography at a kinetic energy of 800 MeV. AB - Flash radiography with 800 MeV kinetic energy protons at Los Alamos National Laboratory is an important experimental tool for investigations of dynamic material behavior driven by high explosives or pulsed power. The extraction of quantitative information about density fields in a dynamic experiment from proton generated images requires a high fidelity model of the proton imaging process. It is shown that accurate calculations of the transmission through the magnetic lens system require terms beyond second order for protons far from the tune energy. The approach used integrates the correlated multiple Coulomb scattering distribution simultaneously over the collimator and the image plane. Comparison with a series of static calibration images demonstrates the model's accurate reproduction of both the transmission and blur over a wide range of tune energies in an inverse identity lens that consists of four quadrupole electromagnets. PMID- 26827357 TI - A tension-torsional fatigue testing apparatus for micro-scale components. AB - Mechanical characterization of micro-scale components under complex loading conditions is a great challenge. To meet such a challenge, a microtension torsional fatigue testing apparatus is developed in this study that specializes in the evaluation of multiaxial fatigue behavior of thin stent wires. The actuation and measurement in two controlled directions are incorporated in the tensile and torsional load frames, respectively, and a thrust air bearing is applied for the coupling of the two frames. The axial deformation of specimens measured by a grating sensor built in the linear motor and by a non-contact displacement detect system is compared and corrected. The accuracy of the torque measurement is proved by torsion tests on thin wires of 316L stainless steel in nominal diameters of 100 MUm. Multistep torsion test, multiaxial ratcheting test, and a fully strain controlled multiaxial cyclic test are performed on 100 MUm and 200 MUm-diameter 316L wires using this apparatus. The capability of the equipment in tension-torsional cyclic tests for micro-scale specimens is demonstrated by the experimental results. PMID- 26827358 TI - A gasdynamic gun driven by gaseous detonation. AB - A gasdynamic gun driven by gaseous detonation was developed to address the disadvantages of the insufficient driving capability of high-pressure gas and the constraints of gunpowder. The performance of this gasdynamic gun was investigated through experiments and numerical simulations. Much more powerful launching capability was achieved by this gun relative to a conventional high-pressure gas gun, owing to the use of the chemical energy of the driver gas. To achieve the same launching condition, the initial pressure required for this gun was an order of magnitude lower than that for a gun driven by high-pressure H2. Because of the presence of the detonation, however, a more complex internal ballistic process of this gun was observed. Acceleration of projectiles for this gun was accompanied by a series of impulse loads, in contrast with the smooth acceleration for a conventional one, which indicates that this gun should be used conditionally. The practical feasibility of this gun was verified by experiments. The experiments demonstrated the convenience of taking advantage of the techniques developed for detonation-driven shock tubes and tunnels. PMID- 26827359 TI - Photoelastic sphenoscopic analysis of crystals. AB - Birefringent crystals are at the basis of various devices used in many fields, from high energy physics to biomedical imaging for cancer detection. Since crystals are the main elements of those devices, a great attention is paid on their quality and properties. Here, we present a methodology for the photoelastic analysis of birefringent crystals, based on a modified polariscope. Polariscopes using conoscopic observation are used to evaluate crystals residual stresses in a precise but time consuming way; in our methodology, the light beam shape, which impinges on the crystal surface, has been changed from a solid cone (conoscopy) to a wedge (sphenoscopy). Since the polarized and coherent light is focused on a line rather than on a spot, this allows a faster analysis which leads to the observation, at a glance, of a spatial distribution of stress along a line. Three samples of lead tungstate crystals have been observed using this technique, and the obtained results are compared with the conoscopic observation. The samples have been tested both in unloaded condition and in a loaded configuration induced by means of a four points bending device, which allows to induce a known stress distribution in the crystal. The obtained results confirm, in a reliable manner, the sensitivity of the methodology to the crystal structure and stress. PMID- 26827360 TI - Multi-channel programmable power supply with temperature compensation for silicon sensors. AB - Silicon Photo-Multipliers (SiPMs) are increasingly becoming popular for discrete photon counting applications due to the wealth of advantages they offer over conventional photo-detectors such as photo-multiplier tubes and hybrid photo diodes. SiPMs are used in variety of applications ranging from high energy physics and nuclear physics experiments to medical diagnostics. The gain of a SiPM is directly proportional to the difference between applied and breakdown voltage of the device. However, the breakdown voltage depends critically on the ambient temperature and has a large temperature co-efficient in the range of 40 60 mV/ degrees C resulting in a typical gain variation of 3%-5%/ degrees C [Dinu et al., in IEEE Nuclear Science Symposium, Medical Imaging Conference and 17th Room Temperature Semiconductor Detector Workshop (IEEE, 2010), p. 215]. We plan to use the SiPM as a replacement for PMT in the cosmic ray experiment (GRAPES-3) at Ooty [Gupta et al., Nucl. Instrum. Methods Phys. Res., Sect. A 540, 311 (2005)]. There the SiPMs will be operated in an outdoor environment subjected to temperature variation of about 15 degrees C over a day. A gain variation of more than 50% was observed for such large variations in the temperature. To stabilize the gain of the SiPM under such operating conditions, a low-cost, multi-channel programmable power supply (0-90 V) was designed that simultaneously provides the bias voltage to 16 SiPMs. The programmable power supply (PPS) was designed to automatically adjust the operating voltage for each channel with a built-in closed loop temperature feedback mechanism. The PPS provides bias voltage with a precision of 6 mV and measures the load current with a precision of 1 nA. Using this PPS, a gain stability of 0.5% for SiPM (Hamamatsu, S10931-050P) has been demonstrated over a wide temperature range of 15 degrees C. The design methodology of the PPS system, its validation, and the results of the tests carried out on the SiPM is presented in this article. The proposed design also has the capability of gain stabilization of devices with non-linear thermal response. PMID- 26827361 TI - Comparative study of electrical breakdown properties of deionized water and heavy water under pulsed power conditions. AB - A comparative study of electrical breakdown properties of deionized water (H2O) and heavy water (D2O) is presented with two different electrode materials (stainless steel (SS) and brass) and polarity (positive and negative) combinations. The pulsed (~a few tens of nanoseconds) discharges are conducted by applying high voltage (~a few hundred kV) pulse between two hemisphere electrodes of the same material, spaced 3 mm apart, at room temperature (~26-28 degrees C) with the help of Tesla based pulse generator. It is observed that breakdown occurred in heavy water at lesser voltage and in short duration compared to deionized water irrespective of the electrode material and applied voltage polarity chosen. SS electrodes are seen to perform better in terms of the voltage withstanding capacity of the liquid dielectric as compared to brass electrodes. Further, discharges with negative polarity are found to give slightly enhanced discharge breakdown voltage when compared with those with positive polarity. The observations corroborate well with conductivity measurements carried out on original and post-treated liquid samples. An interpretation of the observations is attempted using Fourier transform infrared measurements on original and post treated liquids as well as in situ emission spectra studies. A yet another important observation from the emission spectra has been that even short (nanosecond) duration discharges result in the formation of a considerable amount of ions injected into the liquid from the electrodes in a similar manner as reported for long (microseconds) discharges. The experimental observations show that deionised water is better suited for high voltage applications and also offer a comparison of the discharge behaviour with different electrodes and polarities. PMID- 26827362 TI - Note: Measurement system for the radiative forcing of greenhouse gases in a laboratory scale. AB - The radiative forcing of the greenhouse gases has been studied being based on computational simulations or the observation of the real atmosphere meteorologically. In order to know the greenhouse effect more deeply and to study it from various viewpoints, the study on it in a laboratory scale is important. We have developed a direct measurement system for the infrared back radiation from the carbon dioxide (CO2) gas. The system configuration is similar with that of the practical earth-atmosphere-space system. Using this system, the back radiation from the CO2 gas was directly measured in a laboratory scale, which roughly coincides with meteorologically predicted value. PMID- 26827363 TI - Note: A dual temperature closed loop batch reactor for determining the partitioning of trace gases within CO2-water systems. AB - An experimental approach is presented which can be used to determine partitioning of trace gases within CO2-water systems. The key advantages of this system are (1) The system can be isolated with no external exchange, making it ideal for experiments with conservative tracers. (2) Both phases can be sampled concurrently to give an accurate composition at each phase at any given time. (3) Use of a lower temperature flow loop outside of the reactor removes contamination and facilitates sampling. (4) Rapid equilibration at given pressure/temperature conditions is significantly aided by stirring and circulating the water phase using a magnetic stirrer and high-pressure liquid chromatography pump, respectively. PMID- 26827364 TI - Note: Magnetic targeting for enhancement of the activation efficiency of G protein-coupled receptor with a two-pair coil system. AB - Insufficient contact of drug with target cells is a primary reason for limited efficiency of G protein-coupled receptor activation. To overcome this limitation, a simple approach based on magnetic targeting for enhancing drug delivery towards the cell surfaces using magnetic nanoparticles and a two-pair coil system consisting of Helmholtz and Maxwell coils was reported. As a proof of the concept, comparative experiments on G protein-coupled receptor activation process were carried out and results show that the efficiency of G protein-coupled receptor activation can be increased about 6 times in the experiments with the aid of the proposed magnetic targeting system. PMID- 26827366 TI - Note: Spin-exchange optical pumping in a van. AB - The advent of spin-hyperpolarization techniques designed to overcome the sensitivity issue of nuclear magnetic resonance owing to polarization transfer from more ordered systems has recently raised great enthusiasm. However, the out of-equilibrium character of the polarization requires a close proximity between the area of production and the site of use. We present here a mobile spin exchange optical pumping setup that enables production of laser-polarized noble gases in a standalone mode, in close proximity to hospitals or research laboratories. Only compressed air and mains power need to be supplied by the host laboratory. PMID- 26827365 TI - Note: A valve-type piezoelectric reciprocating pump with secondary resonant vibrator. AB - A valve-type piezoelectric diaphragm pump using secondary resonant vibrator is introduced in this paper. The secondary resonant vibrator, which is mainly composed of a first vibrator and a second vibrator, is used to coordinate the frequency incompatibility between piezoelectric elements and check valves. The intermittent vibration of the first vibrator excites the resonant vibration of the second vibrator. The diaphragm in the pump chamber moves with the second vibrator, resulting in chamber volume and pressure variations. Control circuit capable of frequency tracking is designed. Vibration displacement and flow rate changing with driving voltage amplitude, frequency, and backpressure are studied in experiments. The flow rate of a prototype driven by voltage of 712 Vpp is 13.94 ml/min at secondary resonant frequency of 6 Hz. PMID- 26827367 TI - Note: An X-ray powder diffractometer with a wide scattering-angle range of 72 degrees using asymmetrically positioned one-dimensional detectors. AB - An X-ray powder diffractometer has been developed for a time-resolved measurement without the requirement of a scattering angle (2theta) scan. Six one-dimensional detector modules are asymmetrically arranged in a vertical line at a designed distance of 286.5 mm. A detector module actually covers a diffraction angle of about 12 degrees with an angular resolution of 0.01 degrees . A diffracted intensity pattern is simultaneously recorded in a 2theta angular range from 1.63 degrees to 74.37 degrees in a "one shot" measurement. We tested the performance of the diffractometer with reference CeO2 powders and demonstrated diffraction measurements from an operating lithium-air battery. PMID- 26827370 TI - HIV screening: better communication instead of searching for a needle in a haystack? PMID- 26827369 TI - Smoking cessation in cardiac patients: the influence of action plans, coping plans and self-efficacy on quitting smoking. AB - Smoking cessation is the most effective action for cardiac patients who smoke to improve their prognosis, yet more than one-half of cardiac patients continue to smoke after hospital admission. This study examined the influence of action plans, coping plans and self-efficacy on intention to quit and smoking cessation in cardiac patients. Cardiac patients completed a baseline questionnaire (N = 245) assessing demographic characteristics, smoking behavior, intention, self efficacy, relapse self-efficacy and action and coping plans. Six months later (N = 184) continued abstinence from smoking was assessed. Self-efficacy predicted intention to quit smoking and was an indirect predictor of continued abstinence, through intention. Intention to quit smoking and making action plans both directly influenced continued abstinence. Future interventions to facilitate smoking cessation in cardiac patients should put strong emphasis on enhancing self-efficacy and on making specific action plans to increase the likelihood of smoking cessation. PMID- 26827371 TI - [A case of dengue fever that was most likely infected at Yoyogi park in Japan]. PMID- 26827372 TI - FTC scrutinizing homeopathy claims. PMID- 26827373 TI - Feed tote bags implicated in pig disease spread. PMID- 26827374 TI - New funds bolster response to deadly bat fungus. PMID- 26827375 TI - FDA offers aid toward antiparasitic drug approvals. PMID- 26827376 TI - Search tool features veterinary specialists. PMID- 26827377 TI - CDC redesigns Healthy Pets Healthy People website. PMID- 26827378 TI - California wildfires spur veterinary school to action. PMID- 26827379 TI - Banfield launches foundation with grant to AVMF. PMID- 26827380 TI - Reflecting on 100 years of JAVMA. PMID- 26827381 TI - Importance of self-awareness in development of veterinary leaders. PMID- 26827382 TI - Questioning conclusions involving cats with suspected chronic small bowel disease. PMID- 26827383 TI - The authors respond. PMID- 26827384 TI - The claustrum, the external capsule and the extreme capsule of Macaca mulatta. PMID- 26827385 TI - Nerve damage in leprosy. PMID- 26827386 TI - Stigmata of infective endocarditis should be included in the compilation of the risk score. PMID- 26827387 TI - John Fewster and smallpox vaccination. PMID- 26827388 TI - John Fewster and smallpox vaccination--author's reply. PMID- 26827389 TI - Comprehensive Legislative Reform to Protect the Integrity of the 340B Drug Discount Program. AB - The 40B Drug Discount Program (340B Program) is a federally facilitated program that requires drug manufacturers to provide steep discounts on outpatient prescription drugs to qualifying safety net health care providers. The federal program is intended as a safeguard to ensure access to affordable drugs to the indigeut. However, over the last two decades safety net health care providers have exploited financial incentives under the 340B Program at the expense of drug manufacturers and patients, including the most needy and vulnerable populations they are committed to serve. Although the federal government has been applauded for increasing effortsto combat health care fraud and abuse including recovering $3.3 billion in 2014, federal officials and the general public have paid markedly less attention to pervasive abuse of the 340B Program. In 2014, drug purchases of 340B-designated drugs totaled $7 billion and are expected to increase to $12 billion: by 2016 as a result of the expansion of the program under the Affordable Care Act. The 340B Program has completely lost its way, and comprehensive legislation is necessary to realign the program with its intent. PMID- 26827390 TI - "Bringing a Butter Knife to a Gun Fight"? Salience, Disclosure, and FDA's Differing Approaches to the Tobacco Use and Obesity Epidemics. AB - One might expect--given the vastly different look, feel, and function of the ubiquitous (and innocuous) Nutrition Facts panel and the "inflammatory" graphic warning labels for cigarettes--that the statutes establishing such disclosure requirements would exhibit similar disparities. In fact, the relevant provisions of the Nutrition Labeling and Education Act of 1990 and the Family Smoking Prevention and Tobacco Control Act of 2009 are. quite analogous. Like other mandated disclosures, the nutrition label and the cigarette. graphic warnings seek to simultaneously inform and influence consumer decisions. Both statutes grant FDA considerable discretion in.the implementation of the labeling requirements, generally allowing the agency to alter the format and content of the labels as necessary to promote the statutory goals. Thus, the differences in the nutrition and cigarette warning labels are not the product of the statutory schemes alone; rather, they reflect important differences in FDA's interpretation and prioritization of the dual regulatory goals, and in the agency's implicit or explicit assumptions about human behavior. PMID- 26827391 TI - Sweet Knowledge: How Declaring Added Sugars Will Help Consumers Make Informed Food Choices. AB - This paper argues that the Food and Drug Administration (FDA) has the authority to require a declaration of "added sugars" on the nutrition label. FDA has relied on scientific evidence from well-respected sources that concluded that "added sugars" pose a public health concern for Americans; its rule is not arbitrary or capricious. At the same time, there are certain limits on the effectiveness of the "added sugars" rule, especially consumer comprehension. Therefore, FDA should consider more effective front-of-package labeling to clearly communicate the public health risks of "added sugars". PMID- 26827392 TI - Sperm Banking as a Strategy to Reduce Harms Associated with Advancing Paternal Age. AB - Medical studies increasingly link paternal age with disorders in offspring. Associated disorders include autism, bipolar disorder, schizophrenia, and ADHD. Banking one's sperm earlier in life, thereby reducing the effective paternal age at conception, would therefore seem to be a successful strategy for reducing risk to one's eventual offspring. But could a cryopreservation equipment manufacturer or a sperm bank lawfully claim that cryopreservation does more than preserve fertility--that it also prevents disease? This article considers arguments for and against FDA's jurisdiction over such claims, and then makes recommendations for how the agency and Congress should respond. PMID- 26827393 TI - Closing the Door to Lost Earnings Under the National Childhood Vaccine Injury Act of 1986. AB - After a wave of lawsuits against vaccine manufacturers hindered the profitability and production of life-saving vaccines, Congress enacted The National Childhood Vaccine Injury Act of 1986. The Act offers an incentive for individuals to get vaccinated in order to mitigate the population's exposure to disease, while encouraging the continued production of these serums by pharmaceutical companies. Although imperfect, the Vaccine Act fosters promise in filtering out frivolous claims and,provides a central route for due process to the individuals who suffer from a vaccine-related injury. By removing a potential state tort issue to the Federal Circuit, Congress created a reasonably justified avenue for the recovery of damages for injuries and adverse reactions to vaccines. However, this is not to say that the Act can't still be improved. Currently, the Act is silent on whether the death of a child from a vaccine-related injury, before a compensation decision is rendered, should bar the family from recovering for the child's lost earnings. Unless the victim demonstrates a stable source of income that they would have earned had their lives not been interrupted by the adverse reaction to the vaccine, the holding that a minor child may not recover for lost earnings is defensible. However, Congress should revise the statute to issue guidance to clarify its ambiguity. Under the current compensation regime, the standard is too arbitrary to decide that a child who dies before reaching the majority age of 18 has no earning potential. Any line Congress or the Supreme Court tries to draw will be arbitrary, but from an economic, policy, and legal perspective clarity and guidance can be offered to maintain greater flexibility through a case-by case analysis and by applying the modern minimum wage in reference to the child's age. Independent from future earnings awards, Vaccine Act compensation should be amended to increase the cap on these damages to account for inflation since the Act's inception in 1986, to the value of the dollar almost 30 years later. It has been almost three decades since the Act's implementation with no revisions. It is time to modernize the Vaccine Injury Act to better calibrate the amount of damages awarded to the victims of a rare vaccine-related injury. PMID- 26827394 TI - The Right to Try: An Overview of Efforts to Obtain Expedited Access to Unapproved Treatment for the Terminally Ill. PMID- 26827395 TI - Teaching ethics and the Code: Nurse educators weigh in. PMID- 26827396 TI - Aiming for better care. Engaging patients and family members in health decisions, policies. PMID- 26827397 TI - Ethical practice environments, empowered nurses. PMID- 26827398 TI - Policymakers, nurses confronted with proposed measures on assisted suicide. PMID- 26827399 TI - 5 considerations for RNs facing ethical challenges on the job. PMID- 26827400 TI - Ethical leadership. PMID- 26827401 TI - Public health nurses strive to keep community safe, healthy. PMID- 26827402 TI - Words matter. PMID- 26827403 TI - Mary Ellen Patton: Groundbreaking advocate, change agent for staff nurses. PMID- 26827404 TI - Stopping the spread of C. diff. PMID- 26827405 TI - On the front line of quality: The future of health care. PMID- 26827406 TI - Veterans Affairs Secretary McDonald shares vision for nursing. PMID- 26827407 TI - [A Case with the Increased PT-INR after the Addition of Mirtazapine to Warfarin Therapy]. AB - OBJECTIVE: To report a case of warfarinization involving a patient who developed nasal bleeding and an elevated prothrombin time-international normalized ratio (PT-INR) after taking 15 mg of mirtazapine. CASE SUMMARY: A 70-year-old Japanese man with anxiety and irritation was admitted to the ER of our hospital with nasal bleeding. His medical history included atrial fibrillation, treated with warfarin at 3.0 mg a day, hypertension, and diabetus mellitus. He had also been taking mirtazapine at 15 mg. He experienced nasal bleeding 4 days after the initiation of therapy with mirtazapine. His PT-INR markedly elevated from 1.21 before therapy to 7.93 after therapy. Both mirtazapine and warfarin were immediately discontinued by his cardiologist. One week later, PT-INR had normalized (1.00) and the nasal bleeding had resolved. DISCUSSION: The metabolism of warfarin involves several cytochrome P450 isoenzymes, including CYP1A2, CYP2C9, CYP2C19, and CYP3A4. Mirtazapine is metabolized primarily by CYP2D6 and CYP3A4, with lesser contributions by CYP1A2. A competitive enzyme inhibition may occur, with CYP3A4 metabolizing the two drugs. No drug interaction was seen with his other medications. CONCLUSION: The coadministration of mirtazapine and warfarin can result in an increase in the anticoagulant effect of warfarin. This case shows the need to closely monitor potential drug interactions in the elderly, especially those taking mirtazapine and warfarin. PMID- 26827408 TI - [Deceased Schizophrenic Patients--Focus on QT Prolongation]. AB - We retrospectively evaluated factors affecting the lifespan of schizophrenic patients, who are known to have a shorter life expectancy than healthy people, focusing on the relationship with QT prolongation associated with antipsychotics. In a total of 406 patients who died at Asai Hospital the mean age at death was compared between schizophrenic patients and nonpsychiatric patients. In deceased schizophrenic patients, drug-related factors, hematology results, and electrocardiographic findings for 3 years before death were compared with those for the same period in age-matched surviving schizophrenic patients. In addition, QT values in schizophrenic patients and healthy controls were evaluated by age group. The mean age at death was significantly younger in schizophrenic patients (63.4 +/- 2.63 years) than in nonpsychiatric patients (84.0 +/- 0.57 years) (p<0.001). Bivariate analysis between deceased and surviving schizophrenic patients showed significant differences in QT values at 2 years, 1 year, and 0.5 years before death and in AST and ALT values at 0.5.years before death. The incidence of QT prolongation in deceased schizophrenic patients (52.0%) was about twice as high as that in surviving schizophrenic patients (24.5%). Multiple logistic regression analysis suggested that the proportion of deceased patients was higher when QT intervals were longer and ALT values were relatively higher, even if within the normal range. In both schizophrenic patients and medical checkup examinees, QT values were positively correlated with the age (R2 = 0.9061 and 0.9276, respectively), and QT intervals in schizophrenic patients were significantly longer in the 30- to 70-year age groups. In both schizophrenic patients and medical checkup examinees, QT values were positively correlated with the age, and QT intervals in schizophrenic patients were significantly longer than those in medical checkup examinees in the same age groups. Deceased schizophrenic patients showed significantly longer QT intervals from 2 years before death than age-matched surviving schizophrenic patients. QT prolongation may influence the lifespan of schizophrenic patients, which are shorter than those of nonpsychiatric patients. This highlights the importance of following electrocardiographic findings and hematology results of schizophrenic patients over time. PMID- 26827409 TI - [Bipolar Disorder and Major Depressive Disorder in DSM-5: How to Manage in Clinical and Research Fields]. AB - A brief overview of the changes from DSM IV to DSM-5 about "mood disorders" could be: "1. Change of diagnostic category", "2. Addition of new specifiers", and "3. Suggestion of severity assessment tools". The main impact of 1. Change of diagnostic category could be that the "mood disorder" category has disappeared and it has been divided into bipolar disorder and major depressive disorder (MDD). This change was based on the evidence that MDD is distinct from bipolar disorder in the light of genetic and brain structures compared to schizo- phrenia. Some risk-associated genes have been detected related to bipolar disorder and schizophrenia but not to MDD. This could be due to low inter-rater reliability regarding MDD. Furthermore, the specificity of MDD diagnostic criteria is low and various other depression-like disorders that are pathophysiologically different from MDD could be included in the criteria as a phenocopy. Diagnosis from a dimensional point of view with new specifiers and severity assessment tools, described above as points "2" and "3", added to DSM-5 could characterize MDD in more detail and solve this problem related to low inter rater reliability. A dimensional approach could not only identify specific phenotypes in further research but also clinically provide valuable information to put evidence to practical use. In this review, I would like to focus on the significance of the changes in DSM-5 and provide some suggestions on how we should use DSM-5 in clinical and research settings. PMID- 26827410 TI - [The Schizophrenia Spectrum and Other Psychotic Disorders in DSM-5]. AB - Characteristic changes to schizophrenia in DSM-5 are the downgrading of Schneiderian first-rank symptoms and the elimination of subtypes in schizophrenia. Since dimensional evaluation was officially suspended, schizophrenia with a flat face has been described in DSM-5. Recent genomic research, especially involving CNV analysis, has revealed that the categories in DSM are not based on biological information. Because "schizophrenia" was initially just a temporary diagnosis before the clarification of its biological basis, it will be divided when a clear etiology or causal genetic information is found in the future. Meanwhile, we have to follow its changes in a clinical setting due to the lack of alternatives to DSM. Since the practical "perspective" on the disorder is different from research to clarify its etiology, it is impossible, to set one diagnostic criterion to satisfy the requirements from these two perspectives. It will be necessary to use the RDoC in future research for effective categorization. PMID- 26827411 TI - [Impact of DSM-5: Application and Problems Based on Clinical and Research Viewpoints on Anxiety Disorders]. AB - In Japan, the impact of DSM-5 has been greater than we had imagined. The Japanese Society of Psychiatry and Neurology organized a group for translation and the members spent many hours in this volunteer effort over a 2-year period. This highlights the significance of and expectations for DSM-5 in clinical practice in Japan. Regarding anxiety disorders, the highlights of changes from DSM-IV-TR to DSM-5 are as follows. Firstly, the DSM-5 chapter on anxiety disorder no longer includes obsessive-compulsive disorder (which is included with obsessive compulsive and related disorders) or posttraumatic stress disorder and acute stress disorder(which are included with trauma- and stressor-related disorders). However, the sequential order of these chapters in DSM-5 reflects the close relationships among them. Secondly, in DSM-IV, selective mutism and separation anxiety disorder were classified in the section "Disorders Usually First Diagnosed in Infancy, Childhood, or Adolescence." They are now classified as an anxiety disorder. Through these two changes, at the beginning of the chapter, it can be clearly noted that anxiety disorders include disorders that share features of excessive fear and anxiety and related behavioral disturbances. Thirdly, panic disorder and agoraphobia are not associated in DSM-5. Thus, the former DSM-IV diagnoses of panic disorder with agoraphobia, panic disorder without agoraphobia, and agoraphobia without a history of panic disorder are now replaced by two diagnoses, panic disorder and agoraphobia, each with separate criteria. The co occurrence of panic disorder and agoraphobia is now coded with two diagnoses. This change recognizes that a marked number of individuals with agoraphobia do not experience panic symptoms. For the present, this change ends the. controversy over the hierarchy between panic disorder and agoraphobia. The diagnostic criteria for agoraphobia are derived from the DSM-IV descriptors for agoraphobia, although the clarification of fears from two or more agoraphobia-related situations is now required, because this is a robust means for distinguishing agoraphobia from specific phobias. Also, the criteria for agoraphobia are now extended to be consistent with criteria sets for other anxiety disorders (e.g., a clinician's judgment of the fears as being out of proportion to the actual danger in the situation, with a typical duration of 6 months or more). From the above, these changes from DSM-IV-TR to DSM-5 in anxiety disorders make our judgments faster and more efficient in clinical practice, and DSM-5 is more useful to elucidate the pathology. In this manuscript, we discuss the application and problems based on clinical and research viewpoints regarding anxiety disorders in DSM-5. PMID- 26827412 TI - [Molecular Biology on the Mechanisms of Autism Spectrum Disorder for Clinical Psychiatrists]. AB - While, in general, a certain number of clinical psychiatrists might not be familiar with molecular biology, the mechanisms of mental illnesses have been uncovered by molecular biology for decades. Among mental illnesses, even biological psychiatrists and neuroscientists have paid less attention to the biological treatment of autism spectrum disorder (ASD) than Alzheimer's disease and schizophrenia since ASD has been regarded as a developmental disorder that was seemingly untreatable. However, multifaceted methods of molecular biology have revealed the mechanisms that would lead to the medication of ASD. In this article, how molecular biology dissects the pathobiology of ASD is described in order to announce the possibilities of biological treatment for clinical psychiatrists. PMID- 26827413 TI - More than just tired. Nurses, employers should work together to reduce fatigue, its effects. PMID- 26827414 TI - Stopping the revolving door. Nurses lead, implement strategies to reduce readmissions. PMID- 26827415 TI - Welcoming in the 'Year of Ethics'. RNs named most honest for 13 years. PMID- 26827416 TI - 2015 ANA Membership Assembly. PMID- 26827417 TI - Fighting fear. PMID- 26827418 TI - Preventing obstetric deaths. PMID- 26827419 TI - Preoperative interventions improve cardiac patient outcomes. PMID- 26827420 TI - Prohibiting sale of e-cigarettes. PMID- 26827422 TI - U.S. multi-state measles outbreak. PMID- 26827421 TI - Influenza cases build across country. PMID- 26827423 TI - A look at Physician Compare. PMID- 26827424 TI - Healthy and safe: Facilities take a Pathway to Excellence. PMID- 26827425 TI - Preliminary data released from ANA's HRA. PMID- 26827426 TI - Rotating night shift work can be hazardous to health. PMID- 26827427 TI - What nurses are saying.... PMID- 26827428 TI - New toolkit for CNSs to safely manage alarms. PMID- 26827429 TI - National Organization of Nurses with Disabilities asks: What would you do? PMID- 26827430 TI - Decision-making tool to prevent CAUTIs now available. PMID- 26827431 TI - Barbara Zittel: A strong believer in education and collaboration. PMID- 26827432 TI - Interprofessional task force tackles barriers to clinical training. PMID- 26827433 TI - [MODERN APPROACHES TO THE DIAGNOSIS AND TREATMENT OF CHEMOTHERAPY TOXICITY IN PATIENTS WITH BREAST CANCER]. AB - The use of modern chemotherapy (CT) allowed to achieve significant progress in the treatment of many malignant tumors that were previously considered fatal. Improving the efficiency of the treatment was achieved by the intensification of chemotherapy. However, intensification of chemotherapy regimes provoked increase in the number of side effects of anticancer therapy,which often lead to a decrease in the intensity of the selected mode, the additional financial costs of treating the complications and the formation of the negative attitude of the patient to treatment. Thus, the side effects of chemotherapy are the actual problem of modern oncology. The purpose of this literature review was to investigate the frequency, symptoms and ways to prevent and treat various types of toxicity of chemotherapy. PMID- 26827435 TI - [CONSTITUTION OF THE PERSON AND ITS ROLE IN MEDICINE TODAY]. AB - This article provides an analysis of the medical literature and the results of some of their own research on the human constitution. The main properties of the human constitution are somatotype (body composition), temperament, reactivity. The data where these properties are predictors, causes the development of disorders affect the course and symptoms, the effectiveness of treatment and prevention, and prognosis of diseases and adaptation of patients. PMID- 26827434 TI - [BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF): NEUROBIOLOGY AND MARKER VALUE IN NEUROPSYCHIATRY]. AB - In this review current publications about neurobiology and marker value of brain derived neurotrophic factor (BDNF) in neuropsychiatry are analyzed. It is shown that BDNF is an important member of the family of neurotrophins which widely represented in various structures of the CNS. In prenatal period BDNF is involved in all stages of neuronal networks formation, and in the postnatal period its main role is maintaining the normal brain architectonics, involvement in the processes of neurogenesis and realization of neuroprotective functions. BDNF plays an important role in learning and memory organization, food and motor behavior. BDNF brain expression decreases with age, as well as in degenerative and vascular dementias, affective, anxiety, and behavioral disorders. The reducing of BDNF serum, level reflects the decreasing of its cerebral expression and could be used as a neurobiological marker of these pathological processes but the rising of its concentration could indicate the therapy effectiveness. PMID- 26827436 TI - [THE DYNAMICS OF IMMUNOLOGICAL RESULTS OF PATIENTS WITH T-CELL SKIN LYMPHOMAS AND PSORIASIS BY THE THERAPY OF ACTIVATION MECHANISMS SANOGENESIS METHODS]. AB - The therapy T-cell skin lymphoma and psoriasis by the application of activation mechanisms sanogenesis methods, such as: original--a treatment plasmapheresis, a standard heparin infusion; used for the first time--wobenzym; solutions of acid acetic food and sodium bicarbonate; known--the basic sanitations of concomitant diseases, photopheresis caused remissions in 79.6% patients with different stages T-cell skin lymphoma (observed over an 8-year span), and in 67% of patients with psoriasis (observed over an 6-year span). Depuration reactions (phagocytosis, pinocytosis, toxin neutralization) has been activated by detoxication of treatment plasmapheresis and heparin infusions. The topical therapy with wobenzym, solutions of acid acetic food and sodium bicarbonate renewed natural immune barrier of skin. Basic therapy of concomitant diseases enhanced of patient state of health and mobilized compensatory resources. Photopheresis initiated autoimmunization processes by malignant CD4+ lymphocytes. When remission was achieved, the parameters of cellular and humoral immunity returned to normal levels, or the parameters made worse in the absence of remission. PMID- 26827437 TI - [THE ROLE OF IMMUNOLOGICAL CHANGES IN ODONTOGENIC CYSTS]. AB - The study involved 67 patients with odontogenic cysts (OC) aged 18 to 45 years, who were divided into groups: Group 1 (n = 67) patients with OC aged 18 to 45 years, group 2--control group, consisted of 20 healthy persons of similar age. We studied the characteristics of immune status and immunoreactivity in patients with odontogenic cysts. Condition of cellular and humoral immunity was assessed by using the methods of direct rosette developing with erythrocytes coated with monoclonal antibodies to CD3+, CD4+, CD8+, CD22+, CD4/CD8 indicators of immunoregulatory index and phagocytic immunity. State of nonspecific resistance was studied by determining the phagocytic activity of neutrophils and their oxygen dependent metabolism in NBT test. The concentration of cytokines (IL-6 and IL-4) in serum was determined by ELISA. During the study we found that in patients with (OC) developed significant changes in the structure of the immune response at the cellular as well as at the humoral level that makes it necessary to develop new individualized preventive measures along with existing therapies OC. PMID- 26827438 TI - [ANTI-Hsp60 ANTIBODIES IN ARTERIAL HYPERTENTION DIFERENT DEGREE OF SEVERITY]. AB - More than 12.1 million people with hypertension (32.2% of the adult population) were registered in Ukraine according to the official statistics on 1 January 2011. The etiopathogenesis of AH is not fully established. Hsp60 is the molecular chaperon/chaperonin, and it's expression significantly increases in response to different kinds of stress (emotional stress, infections, smoking etc). Elevated blood pressure is a mechanical stress to the endothelium and it can induce expression of heat-shock protein 60 (Hsp60) on the endothelial cell surface. Endothelial cells in the vessel wall can be damaged by (auto) immune reactions to Hsp60 present on the cell surface. Elevation of anti-Hsp60 in the circulation is associated with the presence and severity of coronary heart disease, atherosclerosis development, pathological changes in the small vessels of the brain etc etc. Specificity of the anti-Hsp60 antibodies and their role in the pathogenesis of AH has not been established. The aim of this work was to identify the level of anti-Hsp60 antibodies in the sera of patients with AH. 128 patients with AH were examined. To define level of anti-Hsp60 antibodies the sera 39 patients with AH, including 12 clinically healthy individuals (the family history are included the AH cases)--1 group, 19 patients with stage 2--2 group and 8 patients with stage 3--3 group were examined. The control group included 112 blood donors. Anti-Hsp60 antibodies in sera were determined by ELISA and immunobloting (Western-blotting). Recombinant piotein GroEL Escherihia coli (prokaryotic homologue of human Hsp60) and human Hsp60 were used as antigens. Average of levels of antibodies against GroEL and human Hsp60 in the serum of all groups twice exeeded the value of the control (P < 0.001). Antibodies to prokaryotic Hsp60 were prevailed in patients with AH. The seropositive serum to Hsp60 were detectived in patients, that had the risk of the AH complications by ELISA and immunoblotting. In addition, highly reactive IgG anti-Hsp60 antibodies purified by affinity chromatography from human sera of patients with AH recognized GroEL and human Hsp60 in immunoblotting. Elevated levels of anti-Hsp60 antibody in sera of patients with AH stage 3 correlated with pronounced changes in the target organs such as a massive recurrent hemorrhage into the retina, acute ischemic stroke, cardiosclerosis and angionephrosclerosis. It may indicate the involvement of anti-Hsp60 antibodies in the development of the target organ damage. PMID- 26827439 TI - [ACTIVITY OF LIPOPEROXIDATION AND STATE OF ANTIOXYDANT SYSTEM AT THE PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE ON BACKGROUND OF CHRONIC OBSTRUCTIVE LUNG DISEASE]. AB - At the patients with gastroesophageal reflux disease on background of chronic obstructive lung disease before treatment was detected the increase products of lipids peroxidation (LPO) such as malon dialdegide (MDA), dien's conjugates (DC) in the serum blood. The decline of enzymes activity of the antioxydant system (AOS)--catalase (CT) and superoxiddismutase (SOD) was marked. At treatment the generally accepted facilities was marked decline of MDA, DK and KT and SOD activity. But their level was differed from a norm. It testifies to the maintainance of disbalance of LPO-AOS and expedience of preparations with antioxydant activity application. PMID- 26827440 TI - [PATOGENETIC VALUE OF VIOLATIONS FROM GLUTATHIONE SYSTEM AT THE PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS ON A BACKGROUND OF DIABETES MELLITUS TYPE II]. AB - At the patients with nonalcoholic steatohepatitis on a background of diabetes mellitus type 11, after completion of the generally accepted medical treatment there was no normalization of indexes of the glutation system (the level of recovered glutation and activity of enzymes the glutation redox--system was saved decreased), that in a clinical plan was represented in a presence unstable clinical and biochemical remission of disease. PMID- 26827441 TI - [ROLE OF BIOMARKERS IN ESTIMATION OF RENAL TUBULOINTERSTITIAL TISSUE DAMAGE IN PATIENTS WITH CHRONIC GLOMERULONEPHRITIS]. AB - AIM: to investigate the relationship between the levels of NGAL and IL-18 in.blood, urine and clinical, morphological parameters reflecting renal tubulointerstitial tissue damage (TTD) in patients with chronic glomerulonephritis (CGN). MATERIALS AND METHODS: We examined 81 patients with CGN. Patients were divided into 2 groups according to the presence of arterial hypertension (AH). Levels of NGAL and IL-18 in blood and urine were determined by the immuno-enzymic method. Data of renal morphological study were used for the analysis of TTD. RESULTS: In patients with CGN and AH we observed more pronounced morphological changes of renal TTD, what coincide with higher levels of NGAL and IL-18 in blood and urine. We found correlations between markers and morphological changes, what allow to use NGAL in blood and urine, IL-18 in blood to estimate renal TTD in CGN. CONCLUSIONS: NGAL in blood most accurately reflects interstitial fibrosis (IF) and tubular basement membrane changes; NGAL in urine- tubular epithelium dystrophy. IL-18 in blood is an indicator of dystrophy and necrosis of the tubular epithelium, IF. PMID- 26827442 TI - [EXPRESSION OF GENES, WHICH CONTROL GLUCOSE METABOLISM, IN BLOOD CELLS OF THE OBESE BOYS WITH INSULIN RESISTANCE]. AB - We studied the expression of genes, which responsible for glucose metabolism, in the blood of obese boys with and without of insulin resistance as well as in normal (control) individuals. It was shown that the expression level of PFKFB3 gene is increased, PFKFB1 and INSIG2--is decreased, but HK2 gene--significantly does not change in the blood cells of obese boys with normal insulin sensitivity as compared to control group. Insulin resistance in obese boys leads to up regulation of INSIG2 gene expression as well as to down-regulation of PFKFB1, PFKFB3, and HK2 genes in the blood.cells as compared to obese patients with normal insulin sensitivity. Results of this study provide evidence that obesity affects the expression of the subset of glucose metabolism-related genes in the blood cells and that insulin resistance in obesity is associated with changes in the expression level of PFKFB1, PFKFB3, HK2, and INSIG2 genes, which contribute to the development of insulin resistance as well as glucose intolerance. PMID- 26827443 TI - [CYCLIC VARIATIONS OF LARYNGOTRACHEITIS IN CHILDREN]. AB - It was analyzed the incidences of laryngotracheitis (LT) in children aged 0 to 14 years in Vinnytsya between 1995 and 2008. It was studied seasonal and circadian rhythms of LT in children. The seasonal variations of LT are characterized by two wave curve with peaks in October and March, and with a significant decrease in July and August. The incidences of LT in October and March exceed the incidences of LT in July and August in 2.6 times. Circadian variation of LT is characterized by peak at night. The incidences of LT at night exceed the incidences in the morning in 2.6 times. The total number of the incidences of LT in the evening and at night exceed the total number of the incidences of LT in the morning and in the afternoon in 1.7 times. The maximum of incidences of LT to minimum of incidences of LT per hour ratio is 5:1 in girls compared to 4:1 in boys. PMID- 26827444 TI - STRUCTURAL BASIS OF THE VASCULAR HEMOSTATIC MECHANISM IN THE UTERINE CERVIX. AB - The objective of the study was to investigate the angioarchitectonics and the functional morphology of the vessels of the cervix and to clarify the role of structural features of these vessels in preventing hemorrhaging in parturition during cervical dilatation. Cervixes uteri were obtained from corpses of 30 women of various ages and 5 ablated at labor. Series of histotopographical specimens of the cervixes were processed using histological and histochemical methods. Peculiar features of the angioarchitectonics, histotopography and structure of cervical vessels were encountered. Arteries penetrating the cervix are surrounded by tight muffs of anastomizing veins that are closely adjacent to the arteries. In other cases, the arteries are located within the lumen of veins--"vessels within vessels". Cervical arteries make up subendocervical convolutions. During pregnancy, smooth muscle "cushions" develop in the vessels. The cervix is pierced by a network of veins that divide the cervical tissue into separate stromal "lobules". This peculiar vascular architecture might be important structural basis of the vascular hemostatic mechanism in the neck of the uterus triggered by labor. It prevents vessel rupture, hemorrhaging and amniotic fluid and air embolism during cervical dilatation. The venous network that passes through the cervix makes it easy for the separate stromal "lobules" of the cervix to move relative to each other during cervical dilatation. PMID- 26827445 TI - [ANALYSIS OF ARACHIDONIC ACID RELATIVE CONTENT CHANGES IN ERYTHROCYTES AND PLATELETS PHOSPHOLIPIDS MEMBRANES FEATURES IN CORONARY HEART DISEASE WITH ATRIAL FIBRILLATION PATIENTS]. AB - Erythrocytes and platelets phospholipid membranes fatty acid spectrum was detected in coronary heart disease and atrial fibrillation patients and in patients with coronary heart disease without atrial fibrillation. 87 patients were investigated. Significant decrease in the arachidonic acid relative content in coronary heart disease patients compared with healthy individuals was related. As well as a significant decrease in the arachidonic acid relative content in coronary heart disease and atrial fibrillation patients compared with coronary heart disease patients without atrial fibrillation was related too. These dates may indicate that decreasing relative content arachidonic acid can be possible pathogenetic link in the development of arrhythmias. PMID- 26827447 TI - [DELAYED RESULTS OF ENZYME REPLACEMENT THERAPY, PRESCRIBED BY RESULTS OF 13C TRIGLYCERIDE BREATH TEST]. AB - Maldigestion persists in most patients with chronic pancreatitis (CP). The objective lipase and amylase insufficiency diagnosis is needed to achieve an adequate clinical response to oral pancreatic enzyme substitution therapy. The novel data is presented in the article about the role of 13C-mixed triglyceride breath test as a tool for exocrine pancreatic insufficiency diagnosis, for evaluating fat malabsorbtion in CP patients. 135 patients were included in the investigation. Delayed results of enzyme replacement therapy were estimated after 1 and 2 year of surveillance. It has been shown, that partial recovery of exocrine pancreatic function is possible, and replacement therapy leads to patients nutritional status improving. Thus 13C-triglyceride breath test could be useful tool in clinical practice for CP diagnosis. The test make it possible to choose the initial pancreatic enzyme dosage and are beneficial during the treatment for pancreatic enzyme dose correction. PMID- 26827446 TI - [ABOUT CO-OCCURRENCE OF CRHONIC PANCREATITIS WITH GASTRODUODENAL DISEASES]. AB - The article summarizes clinical features of the course when chronic pancreatitis goes in combination with diseases of gastroduodenal and hepatobiliary systems and features of functional and morphological changes. The article also represents justification of need to include the combined medicine Doktovit (combination of Dexpanthenol and S-methylmethionine) into complex treatment of the pathology, describes mechanism of its gastro protective and reparative action. PMID- 26827448 TI - [POSSIBILITY OF OBTAINING ALLOGENEIC ANTIMENINGOCOCCUS FRESH FROZEN PLASMA AND CONTROL OF ITS QUALITY INDICATORS]. AB - Results of the study identifying the titer of natural antimeningococcus antibodies serogroup B of non-immunized donor population of Zhytomyr Region aged 18-54 years, all AB0 blood groups are presented for further use of these results in the organization of the immune donation. Indicators of quality of antimeningococcus fresh frozen plasma obtained by different methods are characterized. PMID- 26827449 TI - [COGNITIVE DISORDERS IN PATIENTS WITH TRAUMATIC ENCEPHALOPATHY]. AB - As a result of examination 147, patients with traumatic encefalopatiu (TE) were explained the features of cognitive disorders, selected major psihopatologicni syndromes. The moderate cognitive disorders (KP) in patients THOSE, were observed in 40%bolnykh with the psikhorganicheskim syndrome, in 90.6% of patients with the asthenic syndrome, in 90.4%--by likvorodistsirkulyatornym syndrome and 76.1% in patients are cerebral--by focus syndrome. CD complicates, the progress of any post traumatic syndrome, in which they were presented. Moderate cognitive disorders are included in the structure of post traumatic psihorganicnoo syndrome and is a significant dezadaptuucim factor for the patient. PMID- 26827450 TI - [DIAGNOSTICS OF POSITION OF THE MOTOR AND TRIGGER POINTS: OF THE CHEWING MUSCLES FOR ZYGOMATIC COMPLEX FRACTURES]. AB - Existing treatment methods of zygomatic complex fractures, which are complicated by contrac- ture of the masseter as a result of displaced bone fragments, have to be improved. Lack of muscle relaxation leads to the formation of local hypertonicity. In spasmodic muscle fibers varies perfusion and hypoxia occurs, which is accompanied by the release of inflammatory mediators and activation of pain receptors. Over time, areas formed local hypertonicity specific trigger points that contain multiple sensory loci and include one or more sensitive nerve endings. A device for the effective electromyographic study of masseters as a source of their condition and the dynamics of changes in masticatory muscles during patient treatment by improving the fixation system on the face of the patient and the introduction of more perfect spatial coordinate system for mathematical calculations masseter motor position (or triggered) point. Patients were examined before and in the dynamics of treatment according to our methodology, which included proper masseter relaxation, reposition and fixation of bone fragments and further medical therapy. PMID- 26827451 TI - [ANALYSIS OF ULTRASONIC, CYTOLOGICAL AND MORPHOLOGIC RESEARCHES RESULTS OF PATIENTS WITH GRAVES' DISEASE (TOXIC GOITER) DEPENDING ON DISEASE DURATION]. AB - The aim of research is to arrange the results of ultrasonic and cytological researches during long-term drug treatment (more than 1 year) of patients with Graves' disease. From 2008 to 2013 the detailed examination of 220 patients was carried out in Kyiv City Centre for Endocrine Surgery which operates on the basis of the 3d Clinical Hospital. There were established three kinds of echographic patterns which pointed out the ultrasonic changes of the thyroid gland tissue, occurred during the drug treatment. Among 63 (28.6%) patients with long-term drug treatment the development of space-occupying lesions, occurred due to long duration of disease with long-term usage of tyreostatics, was recorded. After the surgical treatment the extracted thyroid gland tissue was subjected to histological study. The papillary carcinoma of thyroid gland was verified in 4 (6,3 %) of 63 patients with space-occupying lesions. The ultrasonic research of thyroid gland in combination with aspiration puncture biopsy and cytological research are the highly informative methods of examination of patients with Graves' disease which allow to objectify the organ structural condition while the disease duration. PMID- 26827452 TI - [DIAGNOSTIC VALUE OF COMBINED USE OF COMBINED METHOD OF ENZYME IMMUNOASSAY AND POLYMERASE CHAIN REACTION TO DETECT OF INTRAUTERINE FETAL INFECTION BY PARVOVIRUS B19]. AB - The combined method of diagnosis parvovirus infection during pregnancy by maternal serum enzyme immunoassay and deoxyribonucleic acid isolation parvovirus B19 polymerase chain reaction in amnniotic fluid and fetal cord blood newborns, can diagnose vertical transmission and anticipate a negative effect on the fetus parvovirus. Lack of maternal IgM antibodies in serum due to parvovirus seroconversion during pregnancy does not exclude the persistence of the virus in the fetus. To analyze the diagnostic value of the method for determining the LHP parvovirus B19 DNA in the amniotic fluid, umbilical cord blood of newborns to determine vertical transmission of parvovirus infection when infected mothers B19 during pregnancy. PMID- 26827453 TI - [RISK FACTORS AND CLINICAL PECULIARITIES OF SECONDARY OLIGOMENORRHEA IN ADOLESCENT GIRLS]. AB - Risk factors related to secondary oligomenorrhea (SOM) are the presence of chronic extragenital pathology, abrupt changes in body mass during a short period of time, a burdened perinatal history at the onset of SOM after a year of regular menstruations. Adolescent girls with SOM differ from their healthy peers by a frequent occurrence of hirsutism, obesity and body mass deficit, uterine hypoplasia. PMID- 26827454 TI - [CONTROL OF HYPERGLYCEMIA IN THE CLINICAL PRACTICE]. AB - The diagnosis of hyperglycemia was based on the fasting plasma glucose, the 2-h value in the 75-g oral glucose tolerance test and the determination of glycated hemoglobin. The purpose of investigation is determination of glycated hemoglobin by patients with the risk of critical condition. For it the three patients groups were investigated: with cerebrovascular diseases, with hyperasotemia and with the renal insufficience. We discoved that hyperglycemia and HbA1c formates important factor in the change of the tone of cerebral arteries. Hyperasotemia makes ponderable percent of distribution in the general population of people. The level of glycated hemoglobin by patients with latent renal insufficience was increased. The determination of HbA1c can use for patients with critical conditions. PMID- 26827455 TI - [STRUCTURAL AND FUNCTIONAL CHANGES MYOCARDIUM HYPERTENSIVE RATS IN APPLYING INDAPAMIDE AND ELLAGIC ACID]. AB - The article investigates the effectiveness of antihypertensive properties of indapamide and ellagic acid in hypertensive rats. As a result of experimental studies determined the effect of drugs on blood pressure and structural recovery of the myocardium of hypertensive rats. Indapamid with ellagic acid reduces the degradation of contractile myofibrils, mitochondria lysis and swelling of the cytoplasm of cardiomyocytes. The study drug is a normalizing effect on the se parameters. The combined use of indapamid and ellagic acid enhances the structural and functional recovery of myocardium energy metabolism normalizes organelles. PMID- 26827456 TI - [YAKTON INFLUENCE ON THE RABBITS CARDIAC ACTIVITY AND SYSTEMI HEMODYNAMIC IN THE CONDITIONS OF 5-FLUOROURACILUM INTOXICATION]. AB - In the experiments on the rabbits the disturbances of cardio and systemic hemodynamic after 5-fluorouracilum administration have been shown. Yakton administercd intravenously in dose 560 mg/ kg one hour before 5-fluorouracilum protects the disturbances of cardio- and systemic hemodynamic data in animals. PMID- 26827457 TI - [PROTEIN CONTENT CHANGES IN RATS' LIVER AND BRAIN UNDER CHRONIC ALCOHOL INTOXICATION]. AB - An electrophoretic investigation of quantitative protein content in rat's' tissyes under chronic alcoholic intoxication has been done. It was shown the significant increase of protein content with molecular mass 55, 48-50, 43-45, 39 41 KDa and the decrease-of protein fractions with molecular mass 46-48, 34-35, 27 30, 16-18 KDa accordingly in liver and brain homogenates of experimental animals. PMID- 26827459 TI - Findings from the 2015 EBRI/Greenwald & Associates Consumer Engagement in Health Care Survey. PMID- 26827460 TI - A Note on Substance Use Disorder Terminology. PMID- 26827461 TI - Substance Use and Child Welfare. PMID- 26827462 TI - Special Foreword: Substance Use and Child Welfare (Second Issue). PMID- 26827463 TI - Promising Results for Cross-Systems Collaborative Efforts to Meet the Needs of Families Impacted by Substance Use. AB - This study is based on data regarding more than 15,000 families served by 53 federal grantees showing that child safety and permanency, parental recovery, and family well-being improve when agencies work together to address the complex needs of families at the intersection of substance abuse treatment and child welfare. Strategies summarized here offer promising collaborative approaches to mitigate the negative outcomes too often experienced by families impacted by substance use disorders. PMID- 26827464 TI - Predictors of Substance Abuse Assessment and Treatment Completion for Parents Involved with Child Welfare: One State's Experience in Matching across Systems. AB - To date, few studies have examined the effect of interagency collaboration on substance abuse assessment ity of Southern California and treatment completion for parents who are involved in child welfare. The purpose of this paper is to: (1) describe a statewide, interagency collaborative program aimed at providing targeted substance abuse assessment and treatment to parents engaged in the child welfare system; (2) document the specialized assessment and treatment outcomes for parents engaged through this collaborative program; and (3) determine factors related to successful treatment completion for parents involved in the child welfare system. This is a retrospective study of an open cohort of 13,829 individuals admitted to the New Jersey Child Protection Substance Abuse Initiative (CPSAI) program from October 1, 2009, through September 30, 2010. Data were drawn from two unique administrative data sources. Multivariate Cox regression models were used to explore factors related to successfil treatment completion for parents involved in the child welfare system. Trend analysis for the total sample in the CPSAI program revealed that, of the 10,909 individuals who received a CPSAI assessment, 59% were referred to treatment. Of those referred to treatment, 40% enrolled in a treatment program. Once enrolled in a treatment program, 55% completed or were in the process of completing substance abuse treatment. These findings suggest that when adequate screening and treatment is available through a streamlined process, many of the ethnic and gender disparities present among other populations of individuals seeking treatment are minimized. Utilizing inherent child welfare case factors appears to be an important motivating element that aids parents during the assessment and treatment process. PMID- 26827465 TI - Examining the Relationships between Family Drug Court Program Compliance and Child Welfare Outcomes. AB - Although the evidence is accumulating to substantiate the successes of Family Drug Courts (FDC), there is little research on the relationship between parent compliance and successful reunification of children with their parent(s). This study looked at data from 206 families participating in a FDC in Sacramento County, California. Four compliance measures were examined individually and collectively, after controlling for participant characteristics, using logistic regression models to determine how FDC participation benchmarks impact child reunification. This study found the best predictors of reunification was participation in support group meetings and negative tests for substance use. These findings indicate that initiatives designed to address the needs of families affected by child maltreatment and substance use should take into account and support engagement in informal, community-based activities as well as formal, clinically focused interventions. PMID- 26827466 TI - Changes in Adult, Child, and Family Functioning among Participants in a Family Treatment Drug Court. AB - Behavioral changes for 76 adults and 115 children from 62 families participating in a Family Treatment Drug Court (FTDC), in either residential or outpatient settings, were studied. Improvements in psychosocial functioning were calculated using a reliable change index (RCI) for family, adult, and child measures. Among outcomes, significant improvements in family functioning were noted and associated with improvements in child development and the likelihood of reunification. Support for FTDCs and implications for future practice and research are discussed. PMID- 26827467 TI - Making It Work Without a Family Drug Court: Connecticut's Approach to Parental Substance Abuse in the Child Welfare System. AB - Parental substance abuse presents, complex challenges for the child welfare system and courts. This article describes the State of Connecticut's experience implementing the Recovery Specialist Voluntary Program (RSVP), a recovery support program designed to confront the problem of parental substance abuse within the child welfare system without, a family drug court. The state-level collaboration efforts, system changes, factors affecting development and implementation of RSVP, program participants, and preliminary outcomes are described. PMID- 26827468 TI - Peer Mentoring in Child Welfare: A Motivational Framework. AB - Peer mentoring interventions for parents with substance use disorders who are involved with the child welfare system are relatively new, complex, individualized interventions and thus need to be understood both in regard to program efficacy and the processes of how they work. This qualitative study of the experiences of parents involved in a parent mentoring program suggested that certain practices helped motivate parents to think and act in ways that supported their goals and child welfare case plans. The three key mentoring practices that emerged were building caring relationships, providing guidance, and putting parents in charge. These practices promoted parents'positive self-beliefs (e.g., worthy of connection, competence), which helped motivate them to participate in services, cope constructively with difficulties, and more effectively manage behaviors and emotions. Drawing on Self-Determination Theory and Basic Psychological Needs Theory (BPNT) in particular, we propose a motivational framework for understanding how peer mentoring facilitates, or undermines, parents'motivation and results in their making progress on various aspects of their child welfare case. Implications for using the motivational model in future program development and evaluation efforts are discussed. PMID- 26827469 TI - Enhancing Family Protective Factors in Residential Treatment for Substance Use Disorders. PMID- 26827470 TI - An Integrated Intervention to Address the Comorbid Needs of Families Referred to Child Welfare for Substance Use Disorders and Child Neglect: FAIR Pilot Outcomes. AB - Despite repeated calls for evidence-based practice to address the co-occurring needs of families referred to the child welfare system for parental substance use disorders and child neglect, limited attention has been given to the rigorous evaluation of such interventions. This paper describes the initial testing of an intervention developed to meet the complex needs of such families. The Families Actively Improving Relationships (FAIR) program and preliminary outcomes are described. The need for integrated interventions is highlighted. PMID- 26827471 TI - Effects of Intensive Family Preservation Services in Rural Tennessee on Parental Hopefulness with Families Affected by Substance Use. AB - This article describes how Building Strong Families in Rural Tennessee (BS-FinRT) increased hopefulness and helped to promote the policy goal of developing a recovery focus among families with vulnerabilities. These outcomes were achieved by implementing collaborative strategies for addressing issues of child safety, substance use, and family stability. Early analyses of the program's outcomes indicated an unexpected positive influence on parent and child hopefulness. Further analyses found that changes in hope between baseline and discharge correlated positively with changes over the same time period in problem severity, general functioning, and mental health symptomology. PMID- 26827473 TI - Substance Use and Child Welfare. PMID- 26827472 TI - A Note on Substance Use Disorder Terminology. PMID- 26827474 TI - Special Foreword: Substance Use and Child Welfare (First Issue). PMID- 26827475 TI - How Many Families in Child Welfare Services Are Affected by Parental Substance Use Disorders? A Common Question that Remains Unanswered. AB - Associated with extensive negative outcomes for children, parental substance use disorders are a major concern within the child welfare system. Obtaining actual prevalence rate data has been difficult, however, and there are no recent published reports on this issue. Using a systematic search, this paper examines: (1) Prevalence estimates of parental substance use disorders in the child welfare population; (2) the types of child welfare involvement for reported prevalence estimates; and (3) how prevalence information is being collected. Prevalence rates were found to have a wide range, from 3.9% to 79%, with regional prevalence estimates being higher than national estimates. Prevalence rates of parental substance use disorders varied by type of child welfare involvement of the family and method of data collection. This study points out the need for improvements in prevalence estimates in the United States and national data collection procedures to ensure that child welfare and substance abuse treatment systems are adequately responding to children and families with substance use disorders. PMID- 26827476 TI - Mental Health Disorders among Children within Child Welfare who have Prenatal Substance Exposure: Rural vs. Urban Populations. AB - This study analyzed differences in mental health diagnoses among Illinois child welfare-involved youth who have had prenatal substance exposure. Results indicate that youth from the rural area had a significantly higher rate of co-occurring mental health disorders. A multiple regression analysis revealed five significant predictors: living in a rural area, a history of neglect, having Fetal Alcohol Syndrome or an alcohol-related neurodevelopmental disorder, and age. These results have implications for adapting existing treatment models. PMID- 26827477 TI - Co-Occurrence of Parental Substance Abuse and Child Serious Emotional Disturbance: Understanding Multiple Pathways to Improve Child and Family Outcomes. AB - This study is a mixed-methods examination of the prevalence and impact of parental substance abuse among families involved in foster care who have a child with a serious emotional disturbance. Data utilized for this study were both administrative and assessment data collected by case managers and parents as part of a federally funded demonstration project in a Midwestern state. At baseline, parent self-report and case manager ratings of family functioning found that parents affected by substance abuse fared worse in domains related to socioeconomics, parental trauma, parental mental health, and social supports when compared to families without parental substance abuse. Case managers and independent raters scored parents affected by substance abuse higher on effective parenting than parents not affected by substance abuse. While all children in the sample have a serious emotional disturbance, parents and case managers rated children's functioning higher among children whose families were characterized by parental substance abuse. These results suggest that, among families who have children with a serious emotional disturbance and are in foster care, those with and without substance abuse may represent two distinct service groups, each with a unique set of needs and contextual factors. For families with parental substance abuse, findings suggest that an appropriate child welfare response should attend to both children's and parent's behavioral health needs and include strategies that are well matched to the families' socioeconomic and social support needs. PMID- 26827478 TI - Practice-Informed Approaches to Addressing Substance Abuse and Trauma Exposure in Urban Native Families Involved with Child Welfare. AB - Similar to families from other groups, urban-based American Indian and Alaska Native ("Native") family members involved with the child welfare system due to substance abuse issues are also often challenged by untreated trauma exposure. The link between these conditions and the history of genocidal policies aimed at destroying Native family ties, as well as experiences of ongoing discrimination, bring added dimensions for consideration when pro- viding services to these families. Practice-based evidence indicates that the trauma-informed and culturally responsive model developed by the Denver Indian Family Resource Center (DIFRC) shows promise in reducing out-of-home placements and re-referrals in urban Native families with substance abuse and child welfare concerns, while also increasing caregiver capabilities, family safety, and child well-being. This article provides strategies from the DIFRC approach that non-Native caseworkers and supervisors can utilize to create an environment in their own agencies that supports culturally based practice with Native families while incorporating a trauma-informed understanding of service needs of these families. Casework consistent with this approach demonstrates actions that meet the Active Efforts requirement of the Indian Child Welfare Act (ICWA) as well as sound clinical practice. Intensive and proactive case management designed specifically for families with high levels of service needs is a key strategy when combined with utilizing a caseworker brief screening tool for trauma exposure; training caseworkers to recognize trauma symptoms, making timely referrals to trauma treatment by behavioral health specialists experienced in working with Native clients, and providing a consistent service environment that focuses on client safety and worker trustworthiness. Finally, suggestions are put forth for agencies seeking to enhance their cultural responsiveness and include increasing workers' understanding of cultural values, worldview, and historical issues; working from a relational perspective; listening deeply to families' experiences; and being open to incorporating traditional healing and cultural practice into service plans. PMID- 26827479 TI - Sobriety Treatment and Recovery Teams in Rural Appalachia: Implementation and Outcomes. AB - The Sobriety Treatment and Recovery Teams (START) model is designed for families with co-occurring substance use and child maltreatment. This study describes the implementation and outcomes of START in a rural Appalachian county with high rates of poverty, non-medical prescription drug use, and child maltreatment. Despite a severely limited addiction treatment infrastructure at baseline, children served by START were less likely to experience recurrence of child abuse or neglect within 6 months or re-enter foster care at 12 months compared with a matched control group. PMID- 26827480 TI - Effects of a Rural Family Drug Treatment Court Collaborative on Child Welfare Outcomes: Comparison Using Propensity Score Analysis. AB - Previous studies that have examined the impact of family drug treatment courts (FDTCs) on child welfare outcomes have produced mixed results. This study evaluates the impact of a rural, FDTC collaborative on child welfare outcomes using propensity score analysis. Findings from the study show that children in the treatment group had longer stays in child welfare custody but were substantially less likely to experience future incidents of maltreatment than those in families with parental substance use disorders without these services. PMID- 26827481 TI - Family-Based Recovery: An Innovative In-Home Substance Abuse Treatment Model for Families with Young Children. AB - Family-based in-home treatment can effectively meet the needs of mothers and fathers struggling with the dual challenges of substance abuse recovery and parenting infants and toddlers. This article describes one such program, Family Based Recovery (FBR), which integrates substance abuse treatment for parents and infant mental health intervention with the goal of preventing child maltreatment and family disruption. Program design, implementation, and results are provided. Outcome data suggest that FBR is a promising model. PMID- 26827482 TI - Rethinking Child Welfare to Keep Families Safe and Together: Effective Housing Based Supports to Reduce Child Trauma, Maltreatment Recidivism, and Re-Entry to Foster Care. AB - Large numbers of children who are placed in child protective custody have parents with a substance use disorder. This placement occurs despite evidence that the trauma of removal is associated with poor long-term child outcomes. This article describes a collaborative model of a continuum of housing-based clinical and support services for the whole family that has safely reduced foster care placement. An external evaluation of this pilot in Jackson County, Oregon, found significant differences in subsequent maltreatment, foster care re-entry, and family permanency outcomes favoring the treatment group. After initial external grant funds, this program is continuing and expanding across Oregon due to state legislation, and funding and can be a model for other states. PMID- 26827483 TI - New Approaches for Working with Children and Families Involved in Family Treatment Drug Courts: Findings from the Children Affected by Methamphetamine Program. AB - This is a descriptive study of the Children Affected by Methamphetamine (CAM) grant program, a federally funded effort to improve outcomes through the addition of targeted interventions for 1,940 families, including 2,596 adults and 4,245 children involved in 12 diverse Family Treatment Drug Courts (FTDCs) located across six U.S. states. The majority were children of parents with a primary methamphetamine use disorder. Findings reflect grantees' reporting on 18 performance indicators of child safety and permanency, adult recovery, and family well-being. Additional information gleaned from grantees' biannual reports provides insights about program implementation. Results, drawn from this large and complex dataset, indicate that comprehensively addressing families' needs is associated with better outcomes than those experienced by similarly situated families in grantees' communities and the nation overall. In addition to describing common program components and outcomes, this article presents important lessons learned about implementing evidence-based children's services in the FTDC context, as well as future directions for research and evaluation in this arena. PMID- 26827484 TI - [TRANSFORMATIONS OF LIFE CYCLES IN THE EVOLUTIONARY HISTORY OF TRYPANOSOMATIDS. MACROTRANSFORMATIONS]. AB - The review concerns analysis of life cycle macrotransformations in the evolutionary history of trypanosomatids. The term "macrotransformations" stands for evolutionary processes leading to the establishment of heteroxenous and secondary homoxenous life cycles within Trypanosomatidae. There were three direct macrotransformations in the evolution of the group resulting in the rise of heteroxenous genera Leishmania, Trypanosoma and Phytomonas, and one case of reverse macrotransformation in trypanosomes of T. (b.) brucei group. The issues of the origin, diversity and phylogeny of taxa whose emergence resulted from macrotransformations of life cycles of homoxenous trypanosomatids. PMID- 26827485 TI - [THE DESCRIPTION OF MYXOBOLUS PELECICOLA SP. NOV. (MYXOZOA: MYXOBOLIDAE) FROM PELECUS CULTRATUS (CYPRINIFORMES, CYPRINIDAE)]. AB - Morphological study of myxosporean parasites Myxobolus pelecicola sp. n. from Pele- cus cultratus (L., 1758), is presented. Presporogenic stage not observed. Polysporous, el- lipsoidal. plasmodia up to 1.2 mm in length and 0.1 to 0.4 mm in width develop in the ske- letal musculature. Mature spores elongate oval or oval form in frontal view, lens-shaped in sutural view. Length of spores 16.5 +/- 0.83 (14.9-18.0), width 12.1 +/- 0.63 (11.6-13.3) (n = 50), thickness 7.8 +/- 0.3 (7.4 8.3) um (n = 10). Polar capsules pyriform, unequal, length of large 8.0 +/- 0.44 (7.5-8.8), small 7.6 +/- 0.26 (7.2-7.8), width of large 4.5 +/- 0.22 (4.2-4.7), small 4.0 +/- 0.21 (3.8-4.3) um. Five to 6 distinct filament coils oriented obli- quely to capsule length, found in polar capsule. The length of extruded (in water) filament up to 130 um. Large, but indistinct triangular intercapsular appendix present in spores. Single rodlet inclusion is very often observed in the posterior part of spore. Mucous enve- lope is absent. The type host of Myxobolus pelecicola sp. n. is sabrefish Pelecus cultratus (L., 1758). Type locality: Finnish Bay (60 degrees 05' N 29 degrees 55' E) and Ladoga lake (60 degrees 07' N 32 degrees 19' E), Russia. PMID- 26827487 TI - [QUESTING BEHAVIOR OF HARD TICKS (IXODIDAE) IN ONTOGENESIS]. AB - Literary and own data on questing behavior of larvae, nymphs, and adults in main genera of hard ticks are analyzed. Evolutionary patterns of this behavior and the role of different life stages in this process are discussed. PMID- 26827486 TI - [ANONCHOCEPHALUS OLIGORHIS SP. NOV. (CESTODA: BOTHRIOCEPHALIDEA) FROM OPHIDIFORMES FISHES OF THE ATLANTIC OCEAN]. AB - In presence article new species of genus Anonchocephalus Riggenbach Luhe, 1902 parasitazing on Hoplobrotula gnathopus Regan, 1921 from the south-eastern part of Atlan- tic Ocean is described. The morphometric analysis of species of genus Anonchocephalus is made, a description of new species is provided with emended of generic diagnosis. PMID- 26827488 TI - [FLEAS (SIPHONAPTERA) OF MAMMALS AND BIRDS IN THE GREAT CAUCASUS]. AB - There are 116 species of fleas in the territory of the Great Caucasus. 21 species are parasites of birds, others are the fleas of mammals. Among 41 genera of Caucasus' fauna only Caenopsylla, Phaenopsylla and Araeopsylla are absent in the Great Caucasus. There are 11 endemic species. Fleas of 66 species are distributed along all mountain system. Parasites of some birds and carnivorous mammals, insectivores and rodents live from lowlands till highlands. Some species are living at the forest altitudinal belt, others prefer the foothills and the mid height areas; they are absent atthe highlands. Their hosts may live at all longitudinal belts; the distribution of other species is limited to lowlands in accordance with distribution of their main hosts. PMID- 26827489 TI - NEW DATA ON BIRD HELMINTHS IN MONGOLIA. AB - For the first time the data on helminths in piscivorous birds (the great cormorant and the Mongolian gull) in Mongolia were obtained. Surveys yielded 11 species (Cestoda--2, Trematoda--6, Nematoda--3). The cormorant hosted 5 helminth species, the herring gull--6 species. PMID- 26827490 TI - [TRIGGER, SIGNALING MECHANISM AND END EFFECTOR OF CARDIOPROTECTIVE EFFECT OF REMOTE POSTCONDITIONING OF HEART]. AB - Trigger of remote postconditioning (RP) is high molecular weight peptide(s). Nitric oxide and adenosine act as intermediaries between the peptide and the intracellular structures. The autonomic nervous system is not involved in the RP. In RP signaling mechanism protein kinase C, PI3 kinase, Akt kinase, aldehyde dehydrogenase are involved. A hypothetical end effector of RP is BKca channel. PMID- 26827491 TI - [FUNCTIONAL ACTIVITY OF THE BRAIN INSULIN SIGNALING SYS TEM IN NORM AND IN TYPE 2 DIABETES MELLITUS]. AB - The insulin signaling system of the brain has a key role in the regulation of fundamental cell processes in neurons and controls metabolic processes in the CNS and periphery. In hypothalamic neurons insulin signaling system interacts closely with the other signaling systems regulated by leptin, melanocortin peptides, dopamine, serotonin, and is the key component of the hypothalamic signaling network, which integrates and transforms the central and peripheral signals. The disturbances in the brain insulin system lead to central insulin resistance, which is one of the primary causes of type 2 diabetes mellitus (DM), metabolic syndrome and Alzheimer's disease. The early restoration of the functions of this system provides an effective approach to prevent and treat type 2 DM and neurodegenerative diseases associated to it. In this review the literature data and own results on structural functional organization of the brain insulin signaling system, causes and functional consequences of central insulin resistance, abnormalities of insulin signaling in the CNS and approaches to its restoration in type 2 DM are analyzed and discussed. PMID- 26827492 TI - [A NEW APPROACH FOR FOOD PREFERENCE TESTING IN ANIMAL EXPERIMENTATION]. AB - An article describes the original method allowing to study a mechanism of food preference related to the sensory properties of foods in animals. The method gives a good possibility to select the role of visual and orosensory signaling in food preference as well as to model the processes of physiological and pathological food and drug dependence in animal experiments. The role of discrete food presentation in the formation of the current motivations and food preferences was discussed. PMID- 26827494 TI - [THE INFLUENCE OF CARBON MONOXIDE ON THE PARAMETERS OF PROOXIDANT-ANTIOXIDANT BALANCE DURING HEPATIC ISCHEMIA-REPERFUSION SYNDROME IN RATS]. AB - The influence of carbon monoxide on the blood and liver prooxidant-antioxidant parameters: lipid peroxidation products (conjugated dienes, malondialdehyde, Schiff bases) and antioxidant system parameters (catalase, retinol, alpha tocopherol, glutathione) were investigated in rats during hepatic ischemia reperfusion. Hepatic ischemia was induced by Pringle maneuver for 30 min, reperfusion period was 120 min. It is detected, that hepatic ischemia-reperfusion leads to intensification of lipid peroxidation with declining of antioxidant defense. Infusion of the donor CO before reperfusion period improves the prooxidant-antioxidant balance in the blood and liver. In conclusion, CO increases the antioxidant activity of the blood and liver, decreases lipid peroxidation processes, that's correct oxidative damages during hepatic ischemia reperfusion. PMID- 26827493 TI - [MOLECULAR MECHANISMS OF ERK1/2 KINASES REGULATION IN THE GLUTAMATE- AND GABA ERGIC NEURONS DURING SEIZURE EXPRESSION IN KRUSHINSKY-MOLODKINA RATS]. AB - The aim of the present study was to analyze a role of the ERK1/2 signaling pathway in the regulation of excitation and inhibitory neurons in the hippocampus and the temporal cortex of Krushinsky-Molodkina rats during seizure development finalizing with ataxia. Analysis was done by Western bloting as well as by immunohistochemistry. The results demonstrated significant up-regulation of ERK1/2 activity in the hippocampus in several seconds after sound stimulation. At the same time increased ERK1/2 activity was correlated with enhanced level of SNARE protein SNAP-25 and activation of synapsin I, the proteins which regulate exocytosis machinery. Decreased level of VGLUT2 associated with activation of ERK1/2 and exocytosis proteins supposed activation of glutamate release in the hippocampus, while in the temporal cortex diminished activity of ERK1/2 and synapsin I associated with VGLUT2 up-regulation assumed inhibition of glutamatergic transmission. Our data let us supposed that decreasing of glutamate release in th& temporal cortex could be a trigger for the inhibition of hippocampal glutamatergic system and the beginning of further ataxia stage. Our data demonstrated correlation between expression and activity of exocytosis proteins and ERK1/2 mainly in the glutamategic neurons of the hippocampus and the temporal cortex that let us proposed significant role of ERK1/2 kinases as a positive regulator of glutamate release and as a result initiation of seizure expression. PMID- 26827495 TI - [MECHANISMS OF MODULATION OF REFLEX CONTROL OF BREATHING AT ELEVATED SYSTEMIC LEVEL OF PROINFLAMMATORY CYTOKINE INTERLEUKIN-1beta]. AB - This study explores the hypothesis about the possible involvement of the cyclooxygenase pathway in the effects of interleukin-1beta (IL-1beta) on the breathing pattern and Heuring-Breuer respiratory reflexes. Respiratory frequency (fR), tidal volume (VT) and esophageal pressure were recorded in 29 adult male Wistar rats anaesthetized with urethane. Heuring-Breuer reflexes were tested by airway occlusion at achieving functional residual capacity (inspiratory inhibitory reflex), and at the height of inspiration (expiratory-promoting reflex). It had been shown that an elevation of IL-1beta in the systemic circulation causes an increase in VT, fR, lung ventilation and strengthens respiratory reflexes. These respiratory effects had not been shown if IL-1beta administered after intraperitoneal injection of diclofenac, which had not any significant respiratory effects by itself. Because diclofenac is a non-specific antagonist of cyclooxygenases, it had been concluded that the prostaglandins mediate respiratory effects of IL-1beta in point of fact. PMID- 26827496 TI - [ASSOCIATED RESPIRATORY AND HEMODYNAMICS RESPONSE TO ACUTE NORMOBARIC PROGRESSIVE HYPOXIA IN ANESTHETIZED RATS]. AB - The interdependent reactions of the cardiorespiratory system during experimental simulation of progressive acute hypoxia were studied in anesthetized Wistar rats. The results indicate that the extremely low oxygen content in the inhaled gas mixture to less than 6% lead to terminal sedation and apnea. After the cessation of hypoxic exposure were observed spontaneous autoresuscitation. Effects of progressive hypoxia, is an example of a multi-component interdependent reactions of the cardiorespiratory system, which are based on the respiratory and vasomotor center function disturbance and the predominance of parasympathetic influences on the heart. The obtained data can be used as a model of hypoxic apnea to examine the influence of physiologically active substances on the cardiorespiratory system at disease pathology. PMID- 26827497 TI - [EFFECT OF MELATONIN ON AGE-RELATED DYNAMICS OF THE REACTIVE PROPERTIES OF BONE TISSUE]. AB - The effect of melatonin (MT) on the bone tissue (BT) reactive properties was investigated among 80 male Wistar rats at the age of 3, 9, 12 and 16 months. The reactive properties of BT were judged by its ability to polarization under the influence of the alternating electric current. The value of reactance at the frequency of maximum polarization was used as the indicator of BT reactivity. Experimental animals received daily melatonin (Unipharm Inc., USA) at the rate of 1 mg/kg of body mass for 28 days. Freshly isolated femurs of rats served as a material for investigation. Introduction of MT to rats resulted in a significant increase in bone mass and polarization properties of BT. However, the clear tendency to increase the reactance not more than 2.2 % (p < 0.1) compared with the control group among the 3-month old rats were observed, and the increasing the reactance among 9 and 12-month old rats were 6.3% and 12.1% (p < 0.1), respectively. Most significantly, the reactance increased by 21.8% (p < 0.05) among 15-month old animals. Thus the introduction of MT increased the reactivity of BT. This effect had a clear dependence on the age and appeared more among older animals. PMID- 26827498 TI - [THE INFLUENCE OF HYDROGEN SULFIDE ON COLLAGEN-INDUCED AGGREGATION OF HUMAN PLATELETS]. AB - Study the impact of hydrogen sulfide on collagen-induced platelet aggregation from healthy donors and patients with type 2 diabetes. In healthy individuals, in contrast to patients with type 2 diabetes, NaHS significantly inhibited platelet aggregation. Activators of cAMP signaling (forskolin and phosphodiesterase inhibitor) significantly reduced platelet aggregation in both groups of examinees. NO-synthase inhibitors increased platelet aggregation in healthy volunteers, but not in patients with type 2 diabetes. The presence of H2S donor did not alter the extent of platelet aggregation at high concentrations of cAMP or decreased production of nitric oxide. It is assumed that the antiplatelet effect of H2S is not associated with the effect on the signal system, mediated cAMP or nitric oxide. Change H2S-dependent regulation of platelet aggregation in patients with type 2 diabetes is caused by disorders have been reported with this disease: the increase of intracellular calcium ion concentration, oxidative damage to proteins, hyperhomocysteinemia, glycosylation of key proteins involved in this process. PMID- 26827499 TI - [DYNAMICS OF GAZE FIXATION DURATION AND EVENT RELATED POTENTIALS WHILE PRESENTATION FADING-IN IMAGES AND DISTRACTORS]. AB - A method for studying the dynamics of human visual attention at various stages of image viewing and recognition has been described. The method is based on the presentation of fading-in images and distractors into the foveal part of visual field. Experimental data demonstrate the effect of habituation to the distractor and bimodal distribution of fixation duration in trials with distractor. It is shown that the effect of distractor is dependent on the complexity of the target images. Significant decrease of the latency of component P350 of fixation related potentials while the simultaneous presentation of target images and distractors is detected in the most of EEG recordings except the occipital ones. On the base of the results obtained the development of tests for evaluation of the current state of visual attention of human-operators, whose main current activities must not be disturbed, has been considered. PMID- 26827500 TI - [Translation and comments of the first three tablets of the IGI series]. AB - This paper translates the chapter on eye diseases from the great treatise on therapeutics compiled under Ashurbanipal and found in his royal libraries at Nineveh. As a professional ophthalmologist, I try to analyse and to understand the symptoms and the treatments described in these tablets, while bearing in mind the dangers of retrospective diagnosis. PMID- 26827501 TI - [Nutrition support for patients-servicemen in military-medical organizations of the Ministry of Defence]. AB - Analysis of the state of nutritional support in military medical institutions of the Ministry of Defence of the Russian Federation. In order to study the state of nutritional support chiefs (heads) of anaesthesiology and resuscitation military medical organizations of the Ministry of Defense of the Russian Federation on the practice of Clinical Nutrition were interviewed. These amounts reflect the organization, strategy, equipment and the need for means and methods of nutritional support, depending on the level of the organization, as well as provide a basis for improving the practice of nutritionally metabolic support in critically ill patients. PMID- 26827502 TI - [Features of morbidity community-acquired pneumonia among young recruits]. AB - Were examined 3338 military personnel of the combined training center. 183 of them diagnosed community-acquired pneumonia, in 3155 focal and infiltrative changes in lung tissue were not identified. The analisys of prevalence been made among young recruits of the acute respiratory illness before arriving in part and at the assembly point, foci of chronic infection, smoking, low body weight. 511 military personnel arrived at the training center in the disease state with symptoms of acute respiratory illness. Examined the relationship these risk factor to the development of community-acquired pneumonia in this category of servicemen. PMID- 26827503 TI - [Pre-hospital care for wounded in military conflicts: state and prospects]. AB - Pre-hospital care is one of the most important links in a chain of the military medical tenet. A survival of the most of severe casualties at the scene depends on a good quality and well-timed first aid and paramedic care. Based on the current state of medical equipment and training of the soldiers of the Russian and foreign armies, we summarized the data about the main medical products designed for pre-hospital care, briefly analyzed and compared their effectiveness to the foreign analogues. It is currently obvious, that fundamental changes in First aid kit modification and Medical Bags are warranted according to the reality and soldier's demands in combat operations. Proposals for modernization of military medical equipment were put forward. PMID- 26827504 TI - [Clinical and prognostic aspects of pulmonary sarcoidosis in servicemen]. AB - The authors analysed clinical, radiological and laboratory aspects of respiratory tract sarcoidosis in servicemen, analysed the quality of life, correlation analysis to determine the risk factors for relapse of the disease. It was found that respiratory tract sarcoidosis of I and II stage was diagnosed in 85.5% of servicemen; in 72% of servicemen prevails asymptomatic course of a disease. Despite the prevalence of asymptomatic forms of the disease, the quality of life of servicemen with sarcoidosis has reduced. The factors associated with recurrent disease: age > 35 years; the presence of clinical manifestations; forced vital capacity < 85% of predicted values; systemic glucocorticoid therapy in history. Designed range forecast recurrent course of sarcoidosis in young patients having a high predictive value. PMID- 26827505 TI - [Sympathetic block as a part of the treatment of coronary heart disease (Literature review)]. AB - The given literature review is devoted to the urgent problem of improving the effectiveness of conservative treatment of patients with coronary heart disease through the use of sympathetic blockade. The authors highlight the. current understanding of the morbid physiology of cardiac angina, in particular, pain syndrome, of the state of analgesia in cardiology. Considered in detail the use of thoracic epidural block in case of coronary heart disease, shows the mechanism of action of epidural blockade, clinical features, its antiischemic effect on the myocardium, the impact on hemodynamic. Also described are the possible side effects and complications of epidural blockade. In conclusion, the authors emphasize the prospect of a wide practical application of regional blockade of local anaesthetics and narcotic analgesics in cardiac patients. PMID- 26827506 TI - [Functional status of submariners after short-time submarine raid in the sea]. AB - Short-time sea submarine raids (from a few days to a few weeks), performed during one working cycle, negatively influence on the functional state of the submariners organism. Upon returning to the point of basing the crew involved in the maintenance of the material and performs preparations for further access to the sea. Due to the high workload and lack of time personnel are not held in any correctional and rehabilitation activities, and therefore the time for the next release in the sea functional condition and functional reserves of the body does not have time to fully recover. The transfer of the submarine crew and referral to medical and psychological rehabilitation assumed only after the end of the operating cycle after the crew the task of further voyage. Based on the assessment of the functional systems of the submarine after a short voyage concluded on the need to develop a set of remedial measures for the recovery of submarine crews during inter-cruise period. PMID- 26827507 TI - [Development of different approaches to classification of medical equipment sets]. AB - The authors provided results of the study on approaches to the classification of medical equipment sets for the medical service of the Armed Forces. A retrospective analysis of the formation and development of classifications of first aid kits, medical bags, sets of medical equipment, medical kits and kits is performed. Basic factors influencing the structure and principles of classification sets of medical equipment are detected. The authors present modern classification of sets of medical equipment and the ways of its improvement. PMID- 26827508 TI - [Prospects of the use of mobile MRI scanner in medical service of the Armed Forces]. AB - Computed tomography is currently one of the most informative methods of diagnostics of a broad range of injuries and diseases, as well as an effective additional mean for various surgical interventions thank to intraoperative use. In this regard, the question of the necessity of the use of this diagnostic technology in mobile hospitals is one of the current tasks. The article analyses the experience of the use of mobile CT scanners at the medical service of the armed forces of foreign states and provides calculations indicating the necessity of the introduction of mobile CT scanners into the hospital link. The review and classification of mobile CT scanners have allowed to formulate technical requirements for their hardware capabilities, as well as to draw conclusions about the conditions of their effective use. PMID- 26827509 TI - [The system of selection and training of military-medical staff for the 40th army (1979-1989)]. AB - In December 1979 in order to fulfil their internationalist duty troops and units of the 40th Army of the Armed Forces of the USSR was brought into Afghanistan. For complete and qualitative manning of the army with the military doctors it was needed in a short time to create a system capable to carry out candidates selection, their education and specialized training for work in extreme conditions of combat operations. This system was created in a short time. The article presents information about its features, advantages and problems that had to be solved during the entire period of the Soviet-Afghan war. The complex staff arrangements had allowed solving medical support problems of the 40th Army on the high level. PMID- 26827510 TI - [Hi-tech center of outpatient care (To the 40th anniversary of the Branch N 6 of the Vishnevsky Central military clinical hospital N 3)]. AB - The authors present the history of the branch N 6 of the Federal States Organization "the Vishnevsky Central Military Clinical Hospital N 3" of the Ministry of Defense of the Russian Federation, which dates back to November 1, 1974. Over the past years, organizational and staff structure; and the name of the clinic (45th central polyclinic, 45th central consultative-diagnostic polyclinic, 52nd Advisory Diagnostic Center of Defense) has repeatedly changed, but the core the work stays unchangeable--to continually improve patient care technology, to be the leader in the outpatient care for soldiers, reserve officers (retired), members of their families. The. branch consists of 58 medical and 19 specialized diagnostic departments, including 4 hospital departments, 1845 employee work at the branch. Among them 4 doctors of medical science and 43 candidates of medical sciences, 20 honoured physicians and 10 honoured health workers of republic. 70% of doctors and 93% of nurses have the highest qualification category. To health care in the Branch are more than 110 thousand people. PMID- 26827511 TI - [The contribution of the department of childhood diseases of the S.M.Kirov Military-medical academy to the medical support of students of educational organizations of general education of the Ministry of Defence]. AB - The article is devoted to the 150th anniversary of the department of childhood diseases of the S.M.Kirov Military Medical Academy and reflects on important activity of the department - creation of the system of medical support for students of general education institutions of the Ministry of Defense. The authors emphasize the role of professor M.S.Maslov, as well as other members of the department, in the development of manuals for health maintenance organization of first Suvorov military schools (1944, 1947). The authors also summarize results of the methodological and scientific work, training and improvement of professional skills of medical staff for educational institutions, including the heads of medical service of schools. The role of the department in improving the medical support for educational institutions of secondary education institutions f'the Ministry of Defence of the Russian Federation at the present stage of development of the Armed Forces is described in the given article. PMID- 26827512 TI - [Graduate of the S.M.Kirov Military-medical academy Fedor Levin: on the way to discovery of DNA]. AB - Biochemist Fedor Aronovich LeviN (1869-1940) graduated with honours from the S.M.Kirov Military Medical Academy in St. Petersburg in 1891 where he had received a fundamental knowledge from A.P.Dianin and I.P.Pavlov, and then he immigrated to the US. More than three and a half decades of his successful research at the Rockefeller Institute for Medical Research contributed to the foundation of the doctrine of nucleic acids. Scientists, who continued to research nucleic acids, were awarded the Nobel Prize, but Levin and his contribution were forgotten. The authors of the given article didn't found any source in Russian about this prominent biochemist of the 20th century and member of the Russian scientific school. The purpose of the article is to acquaint the reader with a scientific biography of the scientist. who became, without exaggeration, one of the founders of modern genetics. PMID- 26827513 TI - [Organisation of medical care delivery to citizens, enjoying a right to get medical care at military-medical organisations of the Ministry of Defence of the Russian Federation]. AB - One of the main priorities of the medical service of the armed forces of the Russian federation is a realization of rights for military retirees and members of their families to free medical care. For this purpose was founded a system of organization of medical care delivery at military-medical subdivisions, units and organizations of the ministry of defence of the Russian federation, based on territorial principle of medical support. In order to improve availability and quality of medical care was determined the order of free medical care delivery to military servicemen and military retirees in medical organizations of state and municipal systems of the health care. PMID- 26827514 TI - [Main types of activity of specialists of medical and preventive profile in military hospitals]. AB - Infection prevention in medical organizations is an essential task to ensure quality of medical care and create a safe environment for patients and medical staff. The main task of a specialist of medical and preventive profile in the hospital is to maintain sanitary and epidemiological safety and control fulfillment of a complex of preventive measures. To achieve these goals specialists monitor epidemiological and microbiological fulfilment of the implementation and effectiveness of preventive measures, which allow to except infection entry to the hospital and possible carrying out beyond the hospital, occurrence and spread of disease. An obligatory activity of the specialist of medical and preventive profile in the hospital is a scientific and methodical work. The authors propose adoption of preventive structural subdivisions to the state largest diversified military hospitals. PMID- 26827515 TI - [Modern aspects of surgical treatment of locally advanced pelvic cancer]. AB - The aim of investigation is to improve surgical treatment of patients with locally advanced pelvic cancer. The basis of investigation is 186 patients with locally advanced pelvic cancer. The average age of patients is 65.2 +/- 5.2 years (from 43.7 to 88.4 years). Among them are 112 women and 74 men. In the period from 2007 to 2015 they were carried out combined (101 patients) and expanded (85 patients) surgical intervention in the department of naval surgery of the Military medical academy after S.M.Kirov. Pelvic evisceration was performed in 63 cases. Both patients were performed isolated vascular hyperthermic chemical pelvic perfusion. Indications for plastic surgery of peritoneum pelvic were: total infralitoral pelvic evisceration (9 patients), dorsal infralitoral pelvic evisceration (11 cases) and expanded abdominoperineal rectum extirpation (34 patients). Plastic surgery with autogenouse tissues was performed to 43 patients, with reticulate explants--to 11 patients. The rate of postoperative complications was 40.2%. The rate of postoperative lethality was 8%. Expanded and combined operations of pelvic at patients with locally advanced cancer without absolute contra-indications can be performed irrespective of age. Plastic surgery of peritoneum pelvic after total and dorsal infralitoral pelvic evisceration and expanded abdominoperineal rectum extirpation indicated in all cases. The easiest method is plastic surgery with greater omentum or peritoneum pelvic. Plastic surgery with reticulate explants is performed when autoplastic is impossible. PMID- 26827516 TI - [A new light on professional fitness expertise of patients with highly curable arrhythmia after hi-tech methods of treatment]. AB - The peculiarities of a clinical course, results of pharmacological and interventional treatment in 447 patients with noncoronary cardiac arrhythmias were analyzed. A definition highly curable cardiac arrhythmia is introduced. The high efficiency and safety of the method of radiofrequency ablation in patients with highly curable cardiac arrhythmias that allows soldiers to leave the military service, as well as to enter military service under the contract. Proposed implementation of the control medical examination to conduct endocardial electrophysiological study and the subsequent medical examination to determine the category of fitness for military service not earlier than 6 months after surgery. PMID- 26827517 TI - [The use of a "buffet" style meals in the system of health-resort treatment]. AB - The authors summarized literature sources, concerning modern ideas about the role of nutritional therapy in the system of health-resort treatment. The authors also made a research on the basis of literature, concerning health-resort nutrition divided into two systems-- buffet system and special-order system. On the basis of sanatorium establishments of the Ministry of Defense authors summarized an experience of clinical nutrition in different age groups and categories of patients. On the basis of current regulatory acts were defined forms and methods of meal catering in the Russian Federation. The results of the study are a scientific supposition for substantiation of management decision-making process, which allows to increase an efficiency of health-resort treatment via nutrition therapy. PMID- 26827518 TI - [Peculiarities of sanitary and epidemiological (preventive) measures aimed at contraction and spread control of Ebola virus disease]. AB - Now the Ebola virus continues to extend in the Western Africa. Cases, including with lethal outcomes are also registered in the countries of Europe and America. The probability of drift of this disease on the territory of the Russian Federation, including through the foreign military personnel who is trained in the country isn't excluded. For prevention of drift and distribution in Russia of the illness caused by the Ebola virus the complex of sanitary and anti-epidemic (preventive) actions is developed and introduced in practice of military health care. The specified actions allow to control an epidemiological situation on this infection and can be recommended for use to military medical experts at all levels. PMID- 26827519 TI - [Problematic medical and psychological issues concerning rehabilitation of crews during the after-sea-dutymen period]. AB - The analysis of the causes of lack of effective functioning of the medical and psychological rehabilitation of crew of the Navy in the Pacific Fleet is performed. Possible ways of solving existing problematic issues are suggested. For determination of fatigue and overwork it was suggested to undertake mandatory initial medical and psychological screening examination of crews immediately before the return to the naval base, using a simple and affordable methods of testing. Medical and psychological rehabilitation of soldiers after the long sea voyages proposed to take immediate military sanatorium of the Ministry of Defense of the Russian Federation (on the territorial principle). PMID- 26827520 TI - [Modern aspects of organization of medical support for the Armed Forces]. AB - The challenges that medical service of the Armed Forces of the Russian Federation faces cannot be solved without a new qualitative approach to military and medical support. In order to create a complete organizational system of the medical support, consisting of united process of material flow management and management of accompanying elements, the. structure of the medical support and its equipment must correspond to performed tasks. The article describes a set of activities that are performed in the system of military-medical support and offers some promising approaches, which are supposed to solve assigned tasks imposed upon the center of pharmacy and medical technology and its interaction with superior body control, maintainable and third party organizations. PMID- 26827521 TI - [Cell engineering in nephrology: The current state and prospectives from the point of view of military medicine]. AB - This article is dedicated to the current state and prospectives of cell engineering in nephrology from the point of view of military medicine. The review is based on publications from January 1, 2014, to June 1, 2015, and consists of two parts. In the first part the main directions of the cell engineering development are mentioned. The only two clinical trials existed in the field are discussed in more detail. The second part deals with prospectives of cell engineering in nephrology. It is shown that currently this field is in the stage of preclinical experimentation. Of the two known clinical trials the first has failed to demonstrate any effectiveness of cell engineering, the second--will be completed only at the end of 2016. Also, the review notes an extraordinary cost of cell engineering experiments in nephrology. The analysis of publications allows to come to a conclusion that the future progress in prevention and treatment of acute kidney injury could go not in the direction of cell engineering but rather non-cell technologies. One of. the practical consequence of such a conclusion is a necessity to continue the improvement of already existing methods of machine renal replacement therapy. PMID- 26827522 TI - [Three centuries with the Fleet (to the 300th anniversary of the Saint-Petersburg naval hospital)]. AB - The authors analysed the history of the Saint-Petersburg naval hospital, founded in October, 1715 by Peter the Great, defined its role in the key historical events during organisation of medical, aid delivery to wounded and patients, discussed current tasks, concerning development of hospital art when forming modern image of the navy of the Russian Federation. PMID- 26827523 TI - [Sanitary state of the ships of the Baltic fleet and development of the navy hygiene in the 18th century]. AB - Sanitary and hygienic state of the Baltic navy ships in the 18th century was considered as unsatisfactory due to inappropriate habitation conditions answering hygienic requirements. The reason for the low ship habitation of that time was limited technological possibilities of the sail shipbuilding, lack of appropriate labour, and life and rest conditions for navy servicemen. In fact, wooden ships were not suitable for life activity of the navy crew, but contributed to disease increase. Because of the rapid development of the' navy hygiene and improvement of shipbuilding technologies, sanitary and hygienic state of local navy ships had became improving. With a glance on recommendations, developed by physicians D.P.Sinopeus and A.G.Bakherakht, were made following improvements: were implemented ventilators on ships, daily fumigation of ships rooms, monitoring of personal hygiene. PMID- 26827524 TI - [Change of memory function and decrease of nitric oxide level of whole brain in the transgenic mice expressing human tau 40 with P301L mutation]. AB - OBJECTIVE: To study the mechanism of learning and memory dysfuction in the transgenic mouse expressing human tau 40 isoform with P301L mutation (F10). METHODS: The human tau protein expression and phosphor-tau protein levels were detected with Western blot method. The neurofibrillary tangles were observed with Bielshowsky silver stain. The behavior changes of learning and memory were observed by open field test and passive avoidance test. Acetyleholine level, activities of acetycholinesterase and choline acetyltransferase of whole brain was detected by colorimetry method. The nitric oxide level of whole brain was detected by nitrate enzyme reduction method. RESULTS: Exogenous human tau gene was expressed and an elevation of phosphor-tau protein level in 7 and 3-month transgenic mice's hippocampus andcerebrocortex was observed. The neurofibrillary tangles were observed in cerebrocortex of 7-month transgenic mice; the 7-month transgenic mice also presented an evident reduction of learning and memory ability and nitric oxide level of the whole brain, but not changes in acetylcholine level, acetycholinesterase activity, choline acetyltransferase activity and expression in whole brain. CONCLUSION: Tau transgenic mice (F10) can still inherit their parents' biologiccal characters, and develop learning and memory dysfunction awnodh san obvious decrease in nitric oxide level of whole brain in the 7-month old mice, suggesting a decrease of nitric oxide level of whole brain would be involved in the mechanism of learning and memory dysfunction in these transgenic mice. PMID- 26827525 TI - [Roles of GSK-3beta signling pathway in chrohic morphine tolerance in rat]. PMID- 26827526 TI - [Screening differentially expressed plasma proteins in cold stress rats based on iTRAQ combined with mass spectrometry technology]. AB - OBJECTIVE: Isobaric tags for relative and absolute quantitation (iTRAQ) combined with mass spectrometry were used to screen differentially expressed plasma proteins in cold stress rats. METHODS: Thirty health SPF Wistar rats were randomly divided into cold stress group A and control group B, then A and B were randomly divided into 3 groups (n = 5): A1, A2, A3 and B1, B2, B3. The temperature of room raising was (24.0 +/- 0.1) degrees C, and the cold stress temperature was (4.0 +/- 0.1) degrees C. The rats were treated with different temperatures until 12 h. The abdominal aortic blood was collected with heparin anticoagulation suction tube. Then, the plasma was separated for protein extraction, quantitative, enzymolysis, iTHAQ labeling, scx fractionation and mass spectrometry analysis. RESULTS: Totally, 1085 proteins were identified in the test, 39 differentially expressed proteins were screened, including 29 up regulated proteins and 10 down-regulated proteins. Three important differentially expressed proteins related to cold stress were screened by bioinfonnatics analysis (Minor histocompatihility protein HA-1, Has-related protein Rap-1b, Integrin beta-1). CONCLUSION: In the experiment, the differentially expressed plasma proteins were successfully screened in cold stress rats. iTRAQ technology provided a good platform to screen protein diaguostic markers on cold stress rats, and laid a good foundation for further. study on animal cold stress mechanism. PMID- 26827527 TI - [The role of cell apoptosis mediated by endoplasmic reticulum stress (ERS) of deep tissue injury of pressure ulcer of rats]. AB - OBJECTIVE: To observe the the expression of endoplasmic reticulum stress (ERS) related factors in deep tissue injury (DTI) at pressure ulcer rat and to investigate the ERS mechanism of DTI in muscle tissue and protective effect of 4 phenylbutyric acid (4-PBA) in local tissue. METHODS: Fifty male SD rats were randomly devided into control group, model group, experimental group NS group and PBA group, the experimental groups were divided into 4 d, 7 d, 14 d and 21 d group according to the observation time (n = 5). Rats in the PBA group were administrated with gastric perfusion of 4-PBA after the modeling; the NS group was given normal saline of the same quantity. Using HE staining to observe morphologic character. The expression of glucose regulated protein 78 (GRP78), CHOP, Caspase 12 were detected by immunohistochernical staining. Cell apoptosis was detected by TUNEL assay. RESULTS: HE staining results showed that each group demonstrated compression injury compared with control group: cellular swelling, ompaction of nuclear, and apoptosis in muscle tissue. The new muscle fiber in 4 PBA group fused faster than those in NS group. The number of TUNEL positive cells peaked at 4 day after compression, then got decreased on day 7 in muscle tissue, apoptosis positive cells were diminished after 4-PBA treatment. The immunohistochemical staining results showed that the expression of protein GRP78, CHOP, Caspase 12 peakd 4 d after modeling and decreased gradually. The GRP78, CHOP, Caspase 12 protein expression were significantly higher than those of PBA group at all time points (P < 0.05). CONCLUSION: Cell apoptosis induced by endoplasmic reticulum stress took part in deep tissue injury resulting of pressure ulcer, which mechanism might be related to reducing apoptosis mediated by CHOP, Caspase 12. PMID- 26827528 TI - [Effect of different pressure oxygen pre-breathe in diving decompression sickness of rats]. AB - OBJECTIVE: To investigate the effect of different pressure oxygen pre-breathing in preventing decompression sickness of rats. METHODS: Forty male SD rats were randomly divided into 4 groups: decompression sickness (DCS) group and three oxygen pre-breathing groups with 1 ATA, 2 ATA and 3 ATA pressure respectively. The rats of DCS group were placed in the hyperbaric chamber and the chamber was compressed evenly within 3 minutes to depths of 7 absolute atmosphere(ATA) and held at the designated depth for 60 min, then decompressed (3 min) at constant speed to the surface pressure. After that, the rats were taken out for further detection. While the rats of oxygen pretreatment groups pre-breathed different pressure oxygen for 20 min before entering into chamber. The mortality and behavioral of rats were observed with 30 min post decompression. The dry/wet ratio of the lung, protein levels in the bronchoalveolar lavage fluid (BALF), and the inflammatory cytokine tumor necrosis factor (TNF-alpha) expression were also tested. RESULTS: Compared with that of the DCS group, the mortality and morbidity of oxygen pre-breathe groups didn't change obviously. But the total BALF protein level and the inflammatory cytokine TNF-alpha expression of 1 ATA oxygen pre breathe group were obviously decreased, while the dry/wet ratio of lung as obviously increased instead (P < 0.05). CONCLUSION: Although preoxygenation can' t obviously change the mortality and mobidity of rats, normal pressure oxygen pre breathing can mitigate the protein infiltration in BALF and the expression of inflammatory cytokine in lung tissue. PMID- 26827529 TI - [Effects of periplaneta Americana extract on cadiovascular injury of peroxidization induced by exhaustive exercise in mice]. PMID- 26827530 TI - [Effect of AAVC-I on the migration of human umbilical vein endothelial cells]. AB - OBJECTIVE: To investigate the effect of component I from agkistrodon acutus venomon (AAVC-I) the migration of human umbilical vein endothelial cells (HUVECs), and to elucidate the possible anti-angiogenic mechanism of AAVC-I. METHODS: The effect of AAVC-I on the migration of HUVECs which was cultivated in vitro and treated with AAVC-1 at four concentrations: 0, 20, 40, 80 microg/ml, was observed by methods of scratch wound-healing and Transwell assay. The expression level of mRNA and protein of P-selectin and intercellular cell adhension molecule-I (ICAM-1) were examined by RT-PCR and Western blot assay. RESULTS: Compared with the blank group, the migration ability of HUVECs in each AAVE-I treated group was reduced in a dose-dependent manner, and the expression level of the mRNA and protein of P-selectin and ICAM-1 were decreased. CONCLUSION: AAVC-I inhibits the migration of endothelial cell, which is acted by down-regulation of the expression content of mRNA and protein of P-selectin and ICAM-1. PMID- 26827531 TI - [The experimental study on melatonin gastro intestinal motility and plasma levels of stress hormones in overtraining rat]. AB - OBJECTIVE: To study the effect of melatonin on the gastrointestinal motility and plasma levels of the stress hormone in overtraining rats. METHOD: Thirty adult SD rats were randomly divided into three groups (n = 10): control group, over training group, melatonin intervention group. 30 min before each training, rats in the control and over-training groups were fed with normal saline (15 mg/kg) once a day and 5 times per week, while rats in the melatonin intervention group were administrated with melatonin, perfusion in the intervention group (15 mg/kg). Excessive training group and melatonin intervention group rats were subjected to excessive training at 5 times a week for 6 weeks. After 6 weeks, the gastric emptying rate, small intestinal propulsion ratio and levels of plasma motilin (MTL) and calcitonin gene-related peptide (CGRP), cortisol (CORT) and catecholamines (CA) were observed in all groups. RESULTS: Compared with the control group, the gastric emptying rate, small intestinal propulsion ratio and levels of plasma MTL, CORT and CA were increased significantly (P < 0.01) while the content of CGRP was reduced (P < 0.01) in over-training group. After treated with melatonin, this trend was reversed, that was, the gastric emptying rate, small intestinal propulsion ratio and levels of plasma MTL, CORT and CA were surpressed significantly (P < 0.01) while the content of CGRP was improved obviously (P < 0.01) in over-training group. CONCLUSION: Melatonin plays an important role in protecting gastrointestinal tract from dysfunction, in which MTL, CGRP, CORT and CA are all involved. PMID- 26827532 TI - [The effect of noninvasive positive pressure ventilation on the expression of ubiquitin-proteasome of skeletal muscle in patients with AECOPD]. AB - OBJECTIVE: To investigate the effect of noninvasive positive pressure ventilation( NIPPy) on the gene and protein expression of biquitin-proteasome of skeletal muscle in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD). METHODS: Seven patients with AECOPD by NIPPV were used as the study group, meanwhile, 6 patients with AECOPD who refused NIPPV was the control group. The blood gas analysis, heart rate (HR) and mean arterial pressure (MBp) were monitored before and 14 days after treatment. A skeletal muscle biopsy was performed after 14 days of therapy. The mRNA expression of ribosomal protein S21 (RPS21), Ubiquitin, Ubiquitin combined with enzyme E2 (E2), Ubiquitin ligase E3 (E3) in skeletal muscle cell were measured by RT-PCR. The protein expression of mitochondrial aconitase (AC02), protease C3 (C3), ribosomal protein SLC16 (SLC16) were detected by Western blot. RESULTS: Forteen days after treatment, the patients in NIPPV group got much better improvement in PaCO2, PaO2 and HR than that of the patients.in the control group (P < 0.05). The gene expression of RPS21,Ubiquitin, E2 and E3 in skeletal muscle cell on patients with NIPPV were obviously lower than that of the control group (P < 0.05, P < 0.01). Compared with that of the control group, the protein expression of C3 and AC2 increased significantly in the NIPPV group (P < 0.01). The protein expression of SLC16 was significantly lowered in the treated group (P < 0.01). CONCLUSION: NIPPV can ameliorate the proteasome pathway and energy metabolic disorders in patients with AECOPD. PMID- 26827533 TI - [Effect of ERK1/2 on rat pulmonary artery smooth muscle cells Kv1.5 channel in the process of hypoxia]. AB - OBJECTIVE: To explore the effect of ERK1/2 MAPK pathway on the expression of Kv1.5 channel, a voltage-gated potassium ion channel, in rat pulmonary artery smooth muscle cells (PASMCs) and its mechanisms during the process of hypoxia. METHODS: The PASMCs derived from SD rats were cultivated primarily. The third to sixth generation of PASMCs were divided into 5 groups randomly: (1) Normal group (N); (2) Hypoxic group (H); (3) Demethy sulfoxide(DMSO) group (HD); (4) U0126 group (HU): 10 micromol/L U0126; (5) Anisomycin group (HA): 10 micromol/L anisomycin. There were three dishes of cells in each group. The cells in normal group were cultured in normoxic incubator (5% CO2, 37 degrees C), the cells in other groups were added to 0.05% DMSO in the hypoxic incubator (5% CO2, 2% O2, 37 degrees C), all cells were cultured for 60 h. RT-PCR and Western blot were used to detected the espressions of Kv1.5 mRNA and protein in PASMCs. RESULTS: Compared with N group, the expressions of Kv1.5 mRNA and protein in H, HD and HA groups were reduced significantly (P < 0.05); Compared with H group and HD groups, Kv1.5 mRNA and protein expressions in HU group were increased sharply (P < 0.05). Compared with the HU group, Kv1.5 mRNA and protein expressions in HA groups were significantly lower (P < 0.05). CONCLUSION: Low oxygen reduced Kv1.5 mRNA and protein expressions, U0126 could resistant the Kv1.5 channel lower expression caused by hypoxia. Anisomycin had no significant effect on Kv1.5 channel expression under hypoxia, but the expression of Kv1.5 was still significantly lower than the normal oxygen group. These data suggest that hypoxia may cause hypoxic pulmonary hypertension by interfering ERK1/2 signaling pathway to inhibit Kv1.5 PMID- 26827534 TI - [A study involving antioxidizability and cytotoxicity of two kinds of phenol from Ajania Salicifolia and their mechanisms of apoptosis]. AB - OBJECTIVE: To extract two kinds of phenols 4-hydroxy-3, 5-dimethoxy-4-(2 oxopropyl) cyclohexa-2, 5-dien-l-one and 6-methoxy-5,7-dihydroxy coumarin (named as I and H compounds respectively) from Ajania salicifolia and to investigate their antioxidation and cytotoxicity to tumors and explore their pro-apoptosis mechanism. METHODS: The antioxidant activities of two compounds were assessed by ABTS and DPPH radical-scavenging assays. Two compounds were evaluated for their cytotoxicity against human chronic myelogenous leukemia (K562) cells using the MIT assay. The expression of NF-kappaB P65 mRNA in K562 apoptotic cells was measured by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR. In addition, protein expression levels of the NF-ICB P65, p Akt, Fas, P-catenina and E-cadherin were also measured by Western blot. RESULTS: (1) We found that compound I displayed significant inoxidizability, while compound II had no obvious antioxidizability. (2) In cytotoxicity experiments, compound I didn't display cytotoxicity while compound H displayed obvious cytotoxicity. (3) Compared with the blank group, the expression of NF-kappaB P65 mRNA in K562 cell after treatment with compound II was obviously up-regulated. (4) Compared with the blank group, the expression levels of NF-kappaB P65, Fas, beta-catenina and E-cadherin were significantly increased in compound II treated groups and it appeared obvious dose-effect relationship between the expression of protein and drug concentration. CONCLUSION: Two phenols have obvious antioxidizability and cytotoxicity respectively. On the one hand, the tumor suppressing mechanism of compound II maybe act by up-regulation the expression of NF-kappaB P65 and Fas protein; thereby, affecting the classical Fas apoptosis signaling pathways. On the other hand, it can also up-regulate the expression of protein beta-catenin and E-cadherin, which participate in the adhesion between cells, and accordingly, playing an important role in preventing the proliferation and metastasis of cancer cells. PMID- 26827535 TI - [The effects of prenatal stress on the cell apoptosis after MCAO in adult offspring rats]. AB - OBJECTIVE: To evaluate the effects of prenatal stress on neurological functions after middle cerebral artery occlusion (MCAO) in adult offspring rats. METHODS: Pregnant rats were randomly assigned to prenatal stress treatment, which was exposed to restraint three times daily in the last week of pregnancy, and no prenatal stress treatment. Adult male offspring rats were subjected to transient focal cerebral ischemia by MCAO. They were randomly divided into four groups: sham group, prenatal stress + sham group, MCAO group and prenatal stress + MCAO group (n = 10). After 24 hours of reperfusion, the neurological deficits were evaluated. The infarct size, cell apoptosis and expression of Caspase 3, cleaved Caspase 3 and Bcl-2 were detected. RESULTS: Compared with MCAO group, the neurological deficits, infarct size and apoptotic cells in prenatal stress + MCAO group were increased significantly (all P < 0.05). The expressions of Caspase 3 and cleaved Caspase 3 were much greater in prenatal stress + MCAO group than those of MCAO group, while the expression of Bcl-2 was significantly decreased in prenatal stress + MCAO group compared with MCAO group (all P < 0.05). CONCLUSION: Prenatal stress might exacerbate neuroloeical deficits in the offspring rats after MCAO by increasing cell apoptosis. PMID- 26827536 TI - [The mechanism of anthocyanin to anti-inflammatory and analgesic frnm Ligustrum fruit]. AB - OBJECTIVE: To provide a theoretical basis for the further development of new drugs, the analgesic and anti-inflammatory effects and the liver function in mice of anthocyanin from Ligustrum vicaryi were investigated. METHODS: The 240 experimental mice were splitted equally for 6 kinds of experiments and 40 rats in each kind of experiment were divided into 5 groups (n = 8): normal saline control group (NS); aspirin control group (Asp); high-concentration anthocyanin group (HA); medium-concentration anthocyanin group (MA); low-concentratior anthocyanin group (LA). The analgesia effect of anthocyanin at different concentration was detenmined by hot-plate test and acetic acid writhin test, and the anti inflammatory effect of anthocyanin was performed by ear edema, ahdomen capillary permeability and cotton granuloma. The activities of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) and the contents of nitric oxide (NO) and prostaglandin E2 (PGE2) in blood serum were determined, and the activities of SOD, T-AOC and glutathione peroxidase (GSH-Px) in liver were measured, while the histological changes of liver tissue were observed. RESULTS: The pain threshold of mice was enhanced and the times of twist body wa decreased by medium concentration and high-concentration anthocyanin. The activity of SOD was increased and the conentrs of NO and PGE were reduced in blood serum. High concentration anthocyanin inhibited the ear swelling , the increase of celiac capillary permeability and th granuloma hyperplasia, and increased the activities of SOD and T-AOC while decreased the content of PGE2. The activities of SOD, T AOC. GSH-PX were increased in liver, but the morphology of liver tissues in each group had no significant changes. CONCLUSION: Anthocyanin Ligustrum vicaryi has definite anti-inflammatory and analgesic effects, which is related to increasing the antioxidant capacity and decreasing th contents of NO and PGE2, and has not obvious damage to liver in the range of experimental concentration. PMID- 26827537 TI - [Exploring the active ingredient of Chinese yellow wine which could inhibit the Hcy induced proliferation and migration of vascular smooth muscle cells]. AB - OBJECTIVE: To explore the active ingredients in the Chinese yellow wine could inhibit the proliferation and migration of rat vascular smooth muscle cells induced by homocysteine (Hcy). METHODS: The primary culture and identification of rat vascular smooth muscle cells (VSMCs) was conducted, and the VSMCs in passage 4-7 were used in the following experiments. The VSMCs were divided into 7 groups: control, Hcy (1 mmol/L), Hcy + oligosaccharide, Hcy + polypeptides, Hcy + polyphenols, Hcy + alcohol, Hcy + Chinese yellow wine and were given the corresponding treatment. The proliferation of VSMCs was determined by MTT. Transwell chambers and would healing were employed to test the migratory ability of VSMCs. Wester blot and gelatin zymography were used to investigate the expressions and activities of metal matrix proteinase 2/9 (MMP-2/9) and tissue inhibitor of metalloproteinase 2 (TIMP-2) in VSMCs of each group. RESULTS: Compared with control group, the proliferation, migration and the expression and activity of MMP-2/9 of VSMCs were significantly increased in the VSMCs of Hcy group (P < 0.01). Compared with Hcy group, the proliferation, migration and the expression and activity of MMP-2/9 of VSMCs were significantly decreases in the VSMCs of polypeptides group, polyphenols group and Chinese yellow wine group. However, the expression of TIMP-2 among each group had no significant difference. CONCLUSION: Polypeptides and polyphenols in the Chinese yellow wine could inhibit the proliferation and migration of VSMCs induced by Hcy. PMID- 26827538 TI - [ERK activation effects on GABA secretion inhibition induced by SDF-1 in hippocampal neurons of rats]. AB - OBJECTIVE: To investigate the effect of extracellular regulating kinase (ERK) signaling pathway on the secretion of gamma-aminobutyric acid (GABA) in cultured rat hippocampal neurons induced by stromal cell derived factor-1 (SDF-1). METHODS: The hippocampal neurons of newborn SD rats were cultured and identified in vitro; the phosphorylation level of ERK1/2 was examined by Western blot; ELISA was used to detect the effect of PD98059, a ERK1/2 specific blocker on GABA secretion of cultured hippocampal neurons and Western blot were adopted to measure the protein expression levels of glutamate decarboxylase (GAD65/67) and gamma aminobutyric acid transporter (GAT); after blocking ERK1/2 signaling pathway with PD98059; RT-PCR was used to detect the mRNA expression levels of GAT 1 and GAD65 after treated with PD98059. RESULTS: The levels of ERKl/2 phosphorylation were increased significantly by SDF1 acting on hippocampal neurons, and CX-CR4 receptor blocker AMD3100, could inhibit SDF-1 induced ERK1/2 activation; SDF-1 could inhibit the secretion of GABA in cultured hippocampal neurons, and ERK1/2 specific inhibitor PD98059, could partly reverse the inhibition of GABA secretion by SDF-1. The effects of SDF-1 on cultured hippocampal neurons was to decrease the mRNA genesis of glutamic acid decarboxylase GAD65 and GABA transporter GAT-1, besides, ERK inhibitor PD98059 could effectively flip the effect of SDF-1. The results of Western blot showed that SDF-1 could inhibit the protein expression of GAT-1 and GAD65/67 in hippocampal neurons and the inhibition of GAT-1 and GAD65/67 protein expression could be partially restored by ERK1/2 blocker. CONCLUSION: SDF-1 acts on the CXCR4 of hippocampal neurons in vitro, and inhibits the expression of GAD by activating the ERK1/2 signaling pathway, and this may represent one possible pathway of GABA secretion inhibition. PMID- 26827539 TI - [Effects of inward rectifier potassium channel blockers on EPCs function]. AB - OBJECTIVE: To investigate the effects of inward rectifier potassium channel blockers (BaCl2, CsCl) on the functions of endothelial progenitor cells (EPCs). METHODS: Density gradient centrifugation-isolated rat hone marrow mononuclear cells were cultured in vitro. EPCs were harvested and seeded on six culture dish when cells grew to 3-5 passages. Before testing the EPCs were synchronized with M199, which contain 2% fetal calf serum. In the end, EPCs were treated with different intervention. The experiment mainly included two parts: (1) BaCl2 (100 micromol/L) and free BaC2 of Tyrodes solution; (2) CsCl (1 mmol/L) and control. Cell pretreated with blockers above mentioned for 12 h, then the gene expression of stromal cell-derived factor-1 (SDF-1), epoprotenol (PGI2) were assessed, beyond that the ability of adhesion, migration were assayed with different tests. In addition, the medium was collected when EPCs were treated for 3 days. The levels of SDF-1 were measured by sandwich enzyme-linked immunosorbent assay (ELISA). Going even further, EPCs were treated with the signal pathway blockers in advance, after repeat the above steps, in order to analyze the change of SDF-1 and then discuss its mechanism. RESULTS: Compared with control group, BaCl2, CsCl could increase EPC adhesion and migration to same extent. Moreover, the gene expression of SDF-1, PGI2 was significantly up-regulated and the production of SDF-1 increased evidently. Furthermore, the mechanism of SDF-1 secretion increasing mainly was associated with eNOS signaling pathways. CONCLUSION: Ba2+ and Cs+ play important roles in increasing EPCs functions, such as adhesion, migration and secretion. PMID- 26827540 TI - [Relationship between pulse pressure and atherosclerotic renal artery]. AB - OBJECTIVE: To analyze the relationship between the pulse pressure (PP) and atherosclerotic renal artery stenosis (ARAS) in middle-age and eldery paients with hyperensio, so as to provide the basis for the diagnosis and treatment of ARAS. METHODS: We tetro spectively analyzed the data of 257 patients with hypertension undergoing renal arteriography at General Hospital of PLA between 2009 and 2014. Their mean age was (64.09 +/- 7.81) years. According the results of arteriography, they were divided into two groups: ARAS group (n = 145), and non-ARAS group (n = 112). Their PP and multinomial clinical indexes with ARAS were statistically analyzed. RESULTS: Single factor correlation and Logisitic analysis showed that age, PP, serum creatinine (SCr) levels, and new onset of hypertension after 50 years of age were strongly positively related to ARAS. The age and PP and SCr was a team of continuous variable. CONCLUSION: PP was the first new risk factor of ARAS in middile-aged and elderly patients with hypertension. It is suggested that PP may be a early predictive indicator and a new therapeutic target for ARAS. PMID- 26827541 TI - [Effects of Citalopram on frontal cortical neurons' bax mRNA bcl-2 mRNA expression and cell apoptosis of rat after stress]. AB - OBJECTIVE: To study the effects of Citalopram on the mRNA expression of bax and bel-2 in frontal cortical neurons and on cell apoptosis of rats after stress. METHODS: Twenty-four healthy male SD rats were randomly divided into three groups (n = 8). The control group did no receive any treatment, the stress group was subject to stress and given normal saline and experimental group was given Citalopram irrigation stomach after stress. Rats were forced to swim to establish chronic stress model (15 min/d, 4 weeks), bax, bcl-2 mRNA expression were tested by in situ hybridization technique (ISH), TUNEL assay was used to determine cell apoptosis, Nikon image analysis software were used to measure the number of positive cells in each index. RESULTS: Compared with the control group, the stress group showed a larger number of bax mRNA expressing cells( P < 0.01), a smaller number of bcl-2 mRNA expressing cells (P < 0.01), and the staining intensity of positive cells was significantly reduced( P < 0.01). Compared with the stress group, the experiment group showed more reduced number of bax mRNA positive cells( P < 0.01) and significantly increased bcl-2 mRNA positive cells( P < 0.05), a small amount of positive cells were found, compared with that in the stress group, nuclear condensation in the experimental group was reduced significantly and the staining was obviously weaker( P < 0.01). CONCLUSION: Citalopram significantly antagonizes bax mRNA and potentiatesbcl-2 mRNA protein expression and inhibits apoptosis of rat prefrontal cortical neurons caused by chronic stress, which might be one possible mechanism of Citalopram for prevention and treatment of psychosis caused by chronic stress. PMID- 26827542 TI - [The effects and mechanisms of high glucose on the phenotype transformation of rat vascular smooth muscle cells]. AB - OBJECTIVE: To investigate the effects and mechanisms of high glucose on the phenotype transformation of rat vascular smooth muscle cells (VSMCs). METHODS: VSMCs ere isolated from rat thoracic aorta and the 3rd-5th VSMCs were incubated with normal glucose (5.5 mmol/L), high glucose (25 mmol/L), or high glucose (25 mmol/L) + P38 inhibitor (25 mmol/L +SB203580) for another 24 hours. Then the gene expression of osteopontin (OPN), alpha smooth-actin (alpha-SMA), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9(MMP-9) were assayed by real time RT-PCR, the protein expression of P38 were assayed by Western blot. RESULTS: (1) High glucose promoted the phenotype transformation of VSMCs and up regulated the expression of MMP-2 and MMP-9. (2) High glucose promoted the phosphorylation of P38. (3) SB203580, the inhibitor of P38/MAPK signal pathway, inhibited the effects of high glucose on phenotype transformation and expression of MMP-2 and MMP-9. CONCLUSION: High glucose may promote phenotype transformation of VSMCs via the signal pathway of P38/MAPK. PMID- 26827543 TI - [The antalgic and antiphiogistic function and mechanism of RGDT plaster]. AB - OBJECTIVE: To study the antalgic and antiphlogistic functions and mechanism of ronggudingtong (RGDT) plaster (traditional Chinese medicine). METHODS: The painful models were established with hot plate test or acetic acid writhing and the inflammatory models were established with daubing dimethylbenzene on auricle or injecting formaldehyde in toe or synovial envelope to study the antalgic and antiphlogistic functions of RGDT Plaster. The total protein and leukotriene B4(LTB4) in inflammatory exudate were detected to investigate the antalgic and antiphlogistic mechanism of RGDT plaster. The mice were randomly divided into different groups (n = 11), on the basis of drug using, the indexes of pain threshold, swelling degree were observed. Sixty-six mice were used to establish gasbag synovitis model and randomly divided into normal control group,model control group, positive control group (Voltaren gel 0.8 mg/d)and low/medium/high dosage RGDT plaster treating groups(30 mg/d, 60 mg/d, 120 mg/d). RESULTS: 30 mg/d, 60 mg/d,120 mg/d RGDT plaster could upgrade the pain thresholds, remit auricular and foot swelling (P < 0.05, P < 0.01), and degrade total protein and LTB4 in inflammatory exudates (P < 0.05, P < 0.01). CONCLUSION: RGDT plaster has some antalgic and antiphlogistic functions, and one of the mechanisms is depressing synthesis of LTB4. PMID- 26827544 TI - [The effects of curcumin on PTEN/PI3K/Akt pathway in Ec109 cells]. AB - OBJECTIVE: To investigate the inhibition effect of curcumin on the proliferation of the human esophageal carcinoma cell line Ec109 and its impact on PEN/PI3K/Akt signaling pathway. METHODS: Esophageal carcinoma Ec109 cells were cultured in vitro conventionally and were treated with curcumin at different concentrations. The cell proliferation level was examined by MIT colorimetry, the ultrastructure of curcumin-treated Ec109 cells were detected with transmission electron microscope (TEM) and cell apoptosis was observed by FCM with AnnexinV-FITC/PI double staining. The protein levels of PTEN, Akt, GSK3P and Caspase 3 of curcumin treated Ec109 cells were detected by Western blot. RESULTS: MTT test showed that curcumin could inhibit the proliferation of Ec109 cells in a time and concentration-dependent manner. TEM examination indicated that curcumin could induce Ec109 cell apoptosis. FCM detection showed that Ec109 cell apoptotic rate increased significantly with the increase of drug concentration. On the other hand, curcumin could promote the expression of PTEN, GSK3beta and Caspase 3 yet reduce the expression of Akt. CONCLUSION: Curcumin could obviously up-regulate the expression of PTEN, GSK3beta and Caspase 3, surpress PI3K/Akt signaling pathway and hence inhibit the proliferation of Ec109 cells. PMID- 26827545 TI - [Establishment of RP-HPLC detection method of N-isopropyl oxamate in the serum of plateau pikas]. AB - OBJECTIVE: To explore the intergrating of N-isopropyl oxamate and serum protein and establish a high performance liquid chromatography (HPLC) detection method of N-isopropyl oxamate (specific inhibitor of testis-specific lactate dehydrogenase (LDH-C4)) in the blood of plateau pikas. METHODS: Twenty highland pika 150-200 g, were randomly divided into two groups (n = 10): control group and inhibitor group. Different concentrations of N-isopropyl oxamate were added to examine the intergrating of N-isopropyl oxamate and serum protein. In order to determine its concentration in the pika blood accurately, we used the method of adding trypsin to incubate the serum first, followed by trichloroacetic acid treatment and detecting by HPLC. Results: When the concentrations of N-isopropyl oxamate in the pika serum were added to 0.05 mmol/L, 0.1 mmol/L, 1 mmol/L, 10 mmol/L, 16.7 mmol/L, 33.3 mmol/L and 100 mmol/L, the intergrating rates between N-isopropyl oxamate and plateau pika serum were 100%, 100%, 100%, 86.84%, 54.11%, 40.10% and 20.18%, respectively. The method established in this paper was good on recovery rates, precision and stability. A good linearity was obtained in the range of 0.0125-0.25 mmol/L. When the concentrations of N-isopropyl oxamate in the serum were added to 0. 15 mmol/L,0.3 mmol/L and 1 mmol/L, the recovery rates were 98.05%, 98.98% and 98.12%, respectively; the precision relative standard deviation( RSD) of concentrations were 1.17%, 0.92% and 0.83%, respectively; the stability relative standard deviation (RSD) of concentrations were 1.38%, 1.40% and 0.88%, respectively. The repeatability RSD of the method was 1.76%. Quantitative limit was 0.0125 mmol/L. CONCLUSION: N-isopropyl oxamate has a strong affinity with plateau pika serum protein that can't be accurately determined with common HIPLC method. It can be accurately determined in the blood by adding trypsinto digest the serum protein first, followed by adding trichloroacetic acid to precipitate the protein. PMID- 26827546 TI - [Therapeutic effect of acupuncture treatment on ischemic hypoxic neonate rats with cerebral palsy]. AB - OBJECTIVE: To explore the mechanisms of acupuncture treatment promoting the motor function recovery of neonate rats with cerebral palsy. METHODS: The improved hypoxic-ischemic encephalopathy (HIE) means was performed to establish the model of neonate rats with cerebral palsy. All neonate rats were randomly divided into 3 groups: sham group, model group and acupuncture group (n = 20). We observed and scored motor function of rats, measured the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in serum, and also measured the expression of synaptophysin (SYP) and growth associated protein-43 (GAP-43) in the diseased region of cerebral tissue. RESULTS: The motor function scores (11.3 +/- 0.29) and the serum level of SOD (147.1 +/- 12.7) U/ml in acupuncture treatment group were higher than those of model group ( P < 0.05). The serum level of MDA was lower in acupuncture treatment group than that of model group (P < 0.05). The expression of SYP and GAP-43 in the diseased region of cerebral tissue of acupuncture treatment group were higher than those of model group ( P < 0.05) . CONCLUSION: Acupuncture-therapy could improve the motor function of neonate rats with cerebral palsy by decreasing the content of MDA in serum, increasing the contents of SOD in serum, and prolonging the upregulation of SYP and GAP-43 expressions in hmin tissue. PMID- 26827547 TI - [The role of oxidative inflammatory cascade on pancreatic fibrosis progression in mice induced by DBTC plus ethanol]. AB - OBJECTIVE: To explore the role and mechanism of oxidative inflammatory cascade in pancreatic fibrosis progression of chronic pancreatitis (CP) in mice induced by dibutyltin dichloride (DBTC) plus ethanol. METHODS: Thirty-six KM mice were randomly divided into 2 groups (n = 18): control group and model group (DBTC combined with ethanol). The mice in model group were intravenously injected with DBTC (8 mg/kg) in tail vein and drink 10% ethanol. After modeling 2 weeks, 4 weeks and 8 weeks, the mice were anesthetized and sacrificed, the pathological changes and the degree of fibrosis in the pancreas were observed by HE and Masson staining, the F4/80 expression level were detected by immunohistochemistry, the content of superoxide dismutase (SOD), malondialdehyde(MDA) and myeloperoxidase (MPO) were measured in the pancreatic homogenates. RESULTS: The fibroblasts and macrophages (f4/80 positive staining) could be seen obviously in pancreas of model group at 2 weeks. At 4 weeks and 8 weeks, macrophages infiltration increased and pancreatic tissue was substituted by the proliferation of fibrosis significantly. At every time-point, in pancreatic homogenates SOD was decreased, MDA and MPO markedly increased. There was significant differences between two groups (P < 0.05). CONCLUSION: DBTC injection joint ethanol drinking can successfully establish the model of chronic pancreatitis and pancreatic fibrosis in mice. Oxidative inflammatory cascade plays an important role in the progression of pancreatic fibrosis. PMID- 26827548 TI - [The gift of pharmacopoeias made by Mesaize to the Society of Pharmacists of Rouen]. AB - Pierre-Gregoire Mesaize, a pharmacist of Rouen made an important gift to the Society of pharmacists of Rouen in 1831. 21 Books, mainly foreign pharmacopoeias, constituted this gift. Six were from Germany; five came from United Kingdom, three from Nederland, only two from France, and one from Belgium, one from Switzerland, one from Austria and one from Russia. This diversity of origins was quite informative about the quality of the content of pharmacists' libraries in Rouen at the beginning of the 19th century. Unfortunately these books could not be found nowadays in the Library of the Union of pharmacists of Seine-Maritime. PMID- 26827549 TI - [The end of an era. Fourteen radio sketches for the Pink Pills]. AB - Those sketches, restaured by the French "Institut national de l'audiovisuel", are transcribed and analyzed for the first time. They was probably broadcasted during the summer of 1939 by the private station Radio Gard Nimes. PMID- 26827550 TI - [The pharmaceutical industry in France: the turning point of 1915]. AB - For several convergent reasons, 1915 was a key period for the pharmaceutical industry in France. The overall realization that France was dependent on Germany for chemical and pharmaceutical products came from shortages of key drugs but also from massive use of poison gas for which France was not able to face this unexpected event. France's shortage for chemists properly trained to answer the needs of industry, the weak relationship between industry and faculty, the uncomfortable situation of specialty drugs, the regulations on patents and trademarks were many subjects of controversies which will contribute to the analysis of the source of this French dependence to Germany. It will be at the origin of new orientations after the war for the pharmaceutical industry and the French society. The objective was to be independent for drugs and consequently to resolve the identified issues, as well as to have a dynamic industrial research. The creation and development of several pharmaceutical companies after the war was a more or less direct benefit from the considerations starting in 1915. PMID- 26827551 TI - [And Sarah Felix created "L 'Eau des Fees" and "La Parfumerie des Fees"]. AB - century, the parisian perfumery of Sarah Felix was famous especially for her cosmetic "L'Eau des Fees" ("Water of the Fairies"), a dyeing supposed to give back to the old hair the color of their youth. Sarah Felix, sister of the famous actress Rachel, exercised several jobs before becoming perfumer. At first, she was actress, then she tried ... oyster culture in Normandy ! Abandoning these activities, Sarah Felix became really a businesswoman in Paris. She dedicated herself to perfumery, in particular to "L'Eau des Fees", from 1866. To launch its product, she was associated to competency characters (engineer, pharmacist, physician) and benefited from the protection of the imperial family. A lawsuit between the associates and the 1870 war hindered the company's early days, but "L'Eau des Fees" provided with quality pledges, imposed itself definitely. The "Parfumerie des Fees" completed the range of its cosmetics with creams, powders, etc. Sarah Felix paid attention to present "L'Eau des Fees" as a dye devoid of toxicity. Was it really the case and could il be sold nowadays? These two issues are discussed in the last part. PMID- 26827552 TI - [The pharmaceutical company Choay: an history linked to research and commercialization of biological products]. AB - Eugene Choay, when he created his own company in 1911, had already a large experience in pharmaceutical industry obtained with Maison Frere where he discovered the famous Dentol, well known thank to Poulbot's publicity drawings for this product. But, convinced of the future of biological products and Opotherapy, he decided to invest himself in this area with a totally new process for cold desiccation of organs. The success will be there and several pharmacists from Choay family will take care of the company and bring it to the top of its specialty in Opotherapy. At the beginning of the 1970's, Choay in in full development and has the products, the sites and the human resources for the future. In 1975, 4 therapeutic areas are covered by Choay's products: coagulation, inflammation, dermatology and hepatology. After more than 65 years of independence, Choay group will be finally bought partially and then totally by Sanofi. With the support of Sanofi, Choay created, in 1981, their US subsidiary called Choay Laboratories Inc;, after the NDA approval of sub-cutaneous Calciparine by the FDA. In 1985 Fraxiparine, a low molecular weight heparin discovered by Jean Choay's team, is lauched on the market. All these developments represent an outstanding record a longevity which indicates how perceptive was Eugene Choay and his successors when choosing to invest totally in the therapeutic use of hormones and products acting on coagulation factors. PMID- 26827553 TI - [The presence of charity books in the inventory of the College of Pharmacy]. AB - The inventory of the Library of the College of Pharmacy was redacted in 1781-1782 and was completed in 1787. It contained seven charity books : Toutes les CEuvres Charitables by Philibert Guybert, Les Secrets touchant la Medecine, Le Medecin et le Chirurgien des Pauvres by Paul Dube, La medecine abbreggee en faveur des Pauvres by the same Paul Dube, Le Traite des-Maladies les plus frequentes by Helvetius, Les Remedes faciles & domestiques by Mrs Fouquet, and the Manuel des Dames de Charite by Arnaut de Nobleville and his co-authors. If these seven books were representative of the charity books in France, they only represented 2 percents of the total amount of books mentioned in the inventory. That is not surprising because this kind of books were not redacted for pharmacists but for not educated people. All these books had been published before the middle of the 18th century and the charity books recently published were not present. That comforted the hypothesis that the books of the Library came only from gifts by members of the College at the end of their Professional life. PMID- 26827555 TI - [The plant, which poisoned the World]. PMID- 26827554 TI - [A short biography of Paul Bonet-Maury (1900-1972) or parallel lives of a pharmacist: researcher and judoka]. AB - Pharmacist by training, doctor in sciences and student of Marie Curie, he will be between 1925 and 1965 one of the pioneers of radiobiology, science of the study of the interaction between ionizing radiations and living matter. He will be the initiator of the teaching on the use of radioelements in medicine and pharmacy. At the same time as he develops a scientific work of international level, he makes a commitment prematurely in the judo of which he will be one of the first four French black belts. He founds in 1946 the French Federation of this sport of which he will be president until 1956, year from which he becomes a general secretary of the International Federation of Judo until 1971. PMID- 26827556 TI - [The use of SPACER in the surgical treatment of periendoprosthetic hip infections -own experience]. AB - The work presents the results of the treatment of 6 patients with periendoprosthetic hip infection with the use of the spacer in the Orthopaetic Traumatic Ward between 01. 09. 2010 and 31. 12. 2013. Each case of infection was treated in two stages. In the first stage, the primary endoprothesis and inflammatory site were removed, and SPACER was implanted. In the second stage, after subsidence of clinical and laboratory symptoms of infection, the surgery was performed involving exchange of the SPACER to a revisory endoprothesis . All the patients were administered Vancomicine intravenously from the day of surgery until the results of bacterial culture were obtained. Then the antibiotic was given intravenously according to the antibiogram for 10 days; in case of negative culture, the therapy with Vancmicinewas continued for 10 days. This was followed by the administration of an oral antibiotic according to antibiogram for 6 weeks, and in case of negative culture, Biseptol 2 x 960 mg was given also for 6 weeks. The second stage of the procedure was carried out between the third and sixth month after the first surgery. In 5 patients inflammatory condition subsided, and a functional result was assessed by the patients as good. In one case inflammation did not heal and the patient remains with "hanging hip"; the result of the treatment was assessed as bad. PMID- 26827557 TI - [Evaluation of the renal excretory function using estimated GFR in patients coming to Voivoidship St. Lukas Hospital in Tarnow in the years 2007-2010]. AB - BACKGROUND: Studies concerning chronic kidney disease frequency are becoming of more and more interest. This is connected with an increased morbidity and diagnosis of chronic kidney disease. The aim of this study was an analysis of glomerular filtration rate results in patients coming to Emergency Department (ED) of Voivodship St. Lucas Hospital in Tarnow for various medical reasons. MATERIAL AND METHODS: We analyzed patients admitted to ED between 30th March 2007 and 31st December 2010. In that period 121116 patients were seen in ER (52660 females and 68456 males). A creatinine level test was performed using the kinetic Jaffe method with alkaline picrate. Glomerular filtration rate (eGFR) was automatically calculated using the abbreviated MDRD formula. eGFR was evaluated in 26176 persons aged 18-104 years (average 59 years) which constituted 21.6% of all people coming to the hospital. Due to lack of some data and some mistakes the final analysis was performed on 23845 patients (12472 females (52.3%) and 11373 males (47.4%)). The whole study population was divided according to sex and age range; 18-34 years, 35-64 years and above 65 years. Stratification of kidney failure was done using the classification of stages of chronic kidney disease according to NKF KDOQI. RESULTS: Patients with chronic kidney disease stages 3 to 5 comprised 25.2% of the study population. Patients above 65 years constituted 45.9%. That group had also the greatest number of patients with eGFR below 60 ml/min (stages 3, 4 and 5 respectively 79.6%, 83.2% and 60.3%), mostly females. Patients who had a creatinine test performed and eGFR evaluated were more frequently hospitalized than patients without creatinine and eGFR checking. CONCLUSIONS: Among patients admitted to ED 21.6% had eGFR evaluated which allowed classification of those patients to an appropriate stage of chronic kidney disease. 25.2% patients in that group had renal insufficiency. The majority of patients with renal insufficiency were above 65 years of age and mostly women. People who had eGFR evaluated were more frequently hospitalized. Evaluating eGFR in ED can help in diagnosing chronic kidney disease. PMID- 26827558 TI - [Frameless image-guided brain and spine surgery]. AB - The author discusses the principles and role of frameless image-guided surgery in operative treatment of brain and spine. Short overview of the method is presented in a way comprehensible for medical professionals from outside neurosurgical and orthopaedic fields. The author presents the importance of image-guided technologies in development of minimally invasive and less destructive surgery of brain and spine. PMID- 26827559 TI - Safety helmets for skiers and snowboarders--efficacy, safety and fitting principles. Review of literature. AB - Head trauma is leading cause of mortality after injuries related with skiing and snowboarding. Wearing a helmet is considered to be a primary method to prevent traumatic brain injuries (TBI) among alpine sports participants. This article, based on literature review, determines the efficacy of helmets and safety of their use. It also presents practical principles of proper helmet fitting. A well proven reduction in the risk of TBI connected with helmet use is reported in the literature, ranging from 22 to 60%. Helmet use does not increase the risk of neck and C-spine injury. There is no good evidence to support the claim that use of helmets increases the risk compensation behaviors among participants. Proper fit includes adequate size, non-attenuated peripheral vision and hearing, well adjusted retention system (chinstrap). This factors may influence both efficacy and safety of helmet use. Helmets are recommended for all skiers and snowboarders. PMID- 26827560 TI - [Neoplasms--treat or educate?]. PMID- 26827561 TI - [Epidemiology and etiology of posterior fossa tumors with particular emphasis on astrocytomas from the Malopolska and Podkarpacki regions]. AB - Brain tumors in children are rare compared with other diseases childhood. Virtually every pediatrician working at the local hospital has been in contact or brain tumor diagnosis was that more half of them recognized the posterior fossa tumor. Analysis of surveys showed difficulties in the interpretation of basic neurological symptoms. Lessons learned from these studies point to the fact that the success of the surgery affects mainly the histological type of tumor and its location. It is extremely important to analyze complaints and symptoms young patients, we should listen to the parents of children with, because usually just parents are the first to notice that their offspring something was wrong. PMID- 26827562 TI - [Lightnings--danger while practising sport]. AB - Certain kinds of sporting disciplines are connected with a high risk of the lightning strike. Although most injuries are non-fatal, the transient or permanent damages of the nervous and ciruculatory systems or other internal organs are common. The concomitant psychological trauma may also be crucial. Various cases could be avoided by following simple safety rules. Wide educational programmes how to act during the stormy weather and elaboration of "stormy guidelines" should concern both sportsmen and people responsible for events safety. PMID- 26827563 TI - [57-year-old patient with hypopituitarism and coexisting autommune hypothyroidism polyglandular syndrome--a case report]. AB - A case of 57-year-old patient with hypopituitarism multihormonal whose symptoms occurred after the last birth history of 16 years ago. Completed studies revealed other irregularities on the basis of which ultimately diagnosed with hypothyroidism polyglandular syndrome patients. PMID- 26827564 TI - [A 21-year old patient with hypernatraemia after intracranial tumour surgery--a case report]. AB - The article concerns case of 21-year old patient after intracranial tumour surgery, who was admitted to the internal diseases department due to hypernatraemia. On the basis of the whole clinical status the patient was diagnosed with diabetes insipidus and disturbance of sensation of thirst which may in turn cause hypernatraemia. There were conducted physical examinations as well as some additional tests which allowed the diagnosis of combined pituitary hormone deficiency. In this situation the disorders of sodium level was rebalanced and hormonal substitution in terms of antidiuretic hormone, adrenocortical hormone, thyroid hormone and testosterone was started. PMID- 26827565 TI - [Physician Society in Tarnow is 145 years old]. PMID- 26827566 TI - [Doctor Josef Cyryl Starkel (1807-1875)--founder of the "Physician Circle"--the first scientific physician association in Tarnow (1870)]. PMID- 26827567 TI - [The assessment of factors affecting acute ethanol poisonings clinical status in 1974-1975, 1984-1985 and 2011-2013]. AB - The aim of the study was an evaluation of clinical factors affecting relationship between ethanol concentration and clinical status in case of acute ethanol poisoning in the 70s and the 80s of the 20th century and 2011-2013 y. Ethanol blood concentration was a criterion of ethanol dose, grade of coma was a decisive factor of toxic effect. MATERIAL AND METHODS: 112 patients treated at the Department of Clinical Toxicology Jagiellonian University Medical College in 1974 1975 y, 232 treated in 1984-1985 y and 663 treated in 2011-2013 y because of acute ethanol poisoning were analyzed. The degree of coma was evaluated according to Matthew's scale. Ethanol plasma concentration in each case was measured. RESULTS: The lowest ethanol blood concentrations in the youngest (<19 y) and the oldest (>60 y) groups were noted also the highest in group of adults (30-49 y). The three-gradual relationship between ethanol plasma level and degree of toxic coma was distinguished. However, the average of ethanol blood concentration were statistically significant in every degree of coma in 2011-2013 y. A statistically significant increase in number of patients in 0 coma grade with severe withdrawal symptoms, alcohol psychosis or epilepsy were noted, also decrease of patient in IV degree of coma. CONCLUSIONS: The increase ethanol tolerance in the group of acute ethanol poisoned patients shows their ethanol addiction. PMID- 26827568 TI - [Drug poisonings in children hospitalized in The Regional Hospital No. 2 in Rzeszow in the years 2010-2014]. AB - INTRODUCTION: Drug poisoning is a frequent cause of hospitalization in children and youth. The aim of the study was to evaluate the prevalence of drug poisoning in children in the region of Rzeszow city. MATERIAL AND METHODS: Medical records of paediatric patients hospitalized in The Regional Hospital No. 2 in Rzeszow between 2010 and 2014 was reviewed and data were collected using scientific protocol. The following factors were analyzed: type of medication causing intoxication, the causality of the event, duration and seasonality of hospitalization as well as demographic data, such as the patient's age and sex. RESULTS: Within the analyzed period 295 children (194 girls and 101 boys) aged between 6 months and 18 years were hospitalized due to acute drug poisoning. Nonopioid painkillers, antiepileptic drugs and sedatives, affecting the cardiovascular system were the main classes of ingested medications. A growing phenomenon of recreational use of drugs which induce euphoria, especially dextromethorphan, was observed among young people. CONCLUSIONS: Due to rising incidence of drug poisoning in childhood physicians and pharmacists should extend their efforts to instruct and educate parents and caregivers about correct drag dosing, safe storage conditions and principles of poisoning prevention. PMID- 26827569 TI - [Vitamin K antagonists overdose]. AB - Nowadays, anticoagulant therapy belongs to the most commonly used forms of pharmacotherapy in modern medicine. The most important representatives of anticoagulants are heparins (unfractionated heparin and low-molecular-weight heparin) and coumarin derivatives (vitamin K antagonists--VKA). Next to the many advantages of traditional oral anticoagulants may also have disadvantages. In Poland most often used two VKA: acenocoumarol and warfarin. The aim of the work is the analysis of the causes of the occurrence of bleeding disorders and symptoms of overdose VKA in patients to be hospitalized. In the years 2012 to 2014 were hospitalized 62 patients with overdose VKA (40 women and 22 men). The average age of patients was 75.3 years) and clotting disturbances and/or bleeding. At the time of the admission in all patients a significant increase in the value of the INR was stated, in 22 patients INR result was " no clot detected", on the remaining value of the INR were in the range of 7 to 13.1. On 51 patients observed different severe symptoms of bleeding (hematuria, bleeding from mucous membranes of the nose or gums ecchymoses on the extremities, bleeding from the gastrointestinal tract--as in 5 patients has led to significant anemia and transfusion of concentrated red blood cells. Up on 33 patients kidney function disorder were found--exacerbated chronic renal failure and urinary tract infection. 8 diagnosed inflammatory changes in the airways. On 13 patients, it was found a significant degree of neuropsychiatric disorders (dementia, cognitive impairment), which made impossible the understanding the sense of treatment and cooperation with the patient. In 6 patients the symptoms of overdose were probably dependent on the interaction with the congestants at the same time (change the preparation of anticoagulant, NSAIDs, antibiotics). In 2 cases, the overdose was a suicide attempt in nature. In addition to the above mentioned disorders, on two of those patients diagnosed with a malignant disease. Two patients died, the other has been improving and anticoagulant therapy with VKA was continued, in 4 VKA were changed to low-molecular-weight heparin, and on 4 commissioned new generation anticoagulant (rivaroxaban). PMID- 26827570 TI - [Acute poisoning with levothyroxine in own experience]. AB - Exposure to thyroid products is common, but acute poisonings in adults are rare. Most cases of severe toxicity are related to prolonged, repeated exposure (either inadvertent or deliberate abuse). There are a few reports of toxicity in children following large (greater than 10 mg) single ingestions. Expect significant toxicity in children and adults who have ingested more than 2 to 4 mg of levothyroxine. However, in comorbid elderly patients, the threshold may be lower. In this paper we present acute overdose of levothyroxine in nine adult patients (aged 21-44 years; mean--30.5 years); ingested doses were from 1.2 mg to 15 mg (mean--6.5 mg). Only in three cases (ingested doses were 5.6; 8.0 and 15 mg) minor and mild clinical symptoms were observed and pharmacological treatment was necessary. No severe symptoms were observed in our group. Asymptomatic clinical course in patients who ingested more than 3 mg of levothyroxine probably was related to coingestion of benzodiazepins, beta-blockers, ACE inhibitors and ethanol. Serum free triiodothyronine (T3) level of 20 pg/ml (normal, 4.1 pg/ml) was reported following an overdose of 15 mg levothyroxine in day five. Normalization was observed in day eleven. PMID- 26827571 TI - [Physician attitudes toward the reporting of adverse drug reactions on the Pomeranian region]. AB - INTRODUCTION: The purpose of the study was to explore the attitudes and knowledge about Pharmacovigilance (PhV) and determine the frequency of ADRs reporting by physicians. MATERIALS AND METHODS: This was a questionnaire based survey filled in by 62 physicians. RESULTS: The study has shown the lack of awareness of doctors about important role of adverse drug reporting in drug safety. Moreover, the majority of physicians who are aware how important is the PhV admitted, that they have never reported such reactions in the past. According to physicians, the main factors that discouraged them from reporting such reactions were unclear "yellow card", and a lack of confidence, whether the reaction was indeed caused by a drug. CONCLUSIONS: In order to improve the safety of the drugs there is a need to show important role of adverse reactions reporting for public safety and make clear and easy procedures to report ADRs. PMID- 26827572 TI - [Dichloroacetate--a healing toxin or a toxic drug?]. AB - Dichloroacetate (DCA) is a compound which activity is observed by experimental and clinical toxicologists. DCA is a by-product of chlorination of water, it is toxic to many organs, such as liver, kidneys or nervous system. In a view of its metabolism it is also demonstrated that this substance may be treated as a drug in various medical conditions, such as different types of tumors for example. PMID- 26827573 TI - [Carbon monoxide poisoning in pregnant woman]. AB - Carbon monoxide poisoning is one of the most frequent types of poisoning caused by gases. Exposure of a pregnant woman to carbon monoxide is connected with transmission of this gas to her fetus what may cause oxygen deficiency, and further, the damage to its organs. The article describes a case of carbon monoxide poisoning of a 28-weeks pregnant woman who was treated in a hyperbaric chamber. Therapy was successful and the woman gave birth to a healthy, full term infant. In case of poisoning to a pregnant woman the above seems to be the most advantageous solution. PMID- 26827574 TI - [Intoxication of female patient with generalised cancer in hospital--a case report]. AB - Medical errors are crucial factors influencing hospital mortality. We present a case of 79-year-old female, who was admitted to the hospital due to complications associated with advanced cancer disease. After several days of hospitalization, the woman died as a result of cancer as well as severe drugs intoxication. The investigation showed extremely high concentrations of chlorprothixen and tramadol in the. blood of the patient. This paper describes a number of medical errors made by hospital staff, of which the most significant was an inappropriate drugs policy. PMID- 26827575 TI - [Drug interaction in 63-year-old male sportsman--a case report]. AB - We present a case of 63-year-old male with hypertension and hyperlipidaemia, who was an athlete in the "masters category". Because of interaction between amlodipine and simvastatin, in combination with physical activity, the patient reported: muscle pain, weakness of the muscles, dizziness, and confusion. After amlodipine and simvastatin discontinuation, all symptoms resolved rapidly. CONCLUSIONS: (1) Concomitant use of several drugs by elderly individual patients, the risk of drug--physical activity interactions may occur. PMID- 26827576 TI - [European Union funds and clinical toxicology]. AB - Since 2014 we are heading the third programming period of help from European Union (EU). The new budget will run until 2020. From common resources of EU, 106 billion euro will reach Poland, of which about 82.3 billion to cohesion policy, levelling differences of regional development. Clinical toxicology centres will be able to apply for funding under the allocation for the health service. Polish health service very actively benefited from EU funds in previous programming periods, between 2004-2006, and 2007-2013. Thanks to grants from the EU, a large number of health centres were built or renovated. Unfortunately the needs of hospitals, which were underinvested for many years, exceeded available funds according to UE programmes. Except investment projects, also projects training of health professionals were executed. In the current programming period European Union will still support projects aimed at health service. Clinical toxicology centres should have a try of using this period to fulfil their plans. PMID- 26827577 TI - [BIOLOGICAL PROPERTIES OF BACTERIA OF THE FAMILY ENTEROBACTERIACEAE AS COMPONENTS OF MICROSYMBIOCENOSIS OF THE FIRST INTERMEDIATE HOSTS OF O.FELINEUS]. AB - The objective of the investigation was to study the biological properties (antilysozyme activity (ALA), biofilm formation (BFF), and virulence factors) of different Enterobacteriaceae species isolated from Bithyniidae mollusks and their habitats. A total of 117 strains isolated from Bithyniidae mollusks of the genera Codiella and Bithynia and those from their habitats were the material to be studied. Thus, comparison of the mean values of ALA in Enterobacteriaceae species suggests that the strains isolated from the mollusks and their aqueous habitat did not virtually differ in this indicator. Also, there were no statistically significant differences in the detection rate of the Enterobacteriaceae strains having a pronounced antilysozyme activity and in that of mollusks circulating in the aqueous habitat when compared with the strains isolated from the mollusks. Comparison of BFF in the aqueous bacterial strains and mollusk microbiota representatives revealed the highest values in the former; just lower value was noted in the latter. Soil Enterobacteriaceae isolates had very low BFF values. PMID- 26827578 TI - [OPISTHORCHIASIS AS A PROMOTER OF GASTRIC CARCINOGENESIS]. AB - The paper presents an experimental model of gastric cancer in the presence of chronic opisthorchiasis, which has been created to study its possible role in gastric carcinogenesis. The performed investigation has supported the hypothesis that opisthorchiasis plays a promoting role in the development of experimental gastric cancer. A larger number of experimental hamsters receiving the carcinogen methylnitronitrosoguanidine (MNNG) developed earlier gastric tumors in. the presence of chronic opisthorchiasis than the control animals in the experiment. PMID- 26827579 TI - [MOSQUITOES (DIPTERA, PSYCHODIDAE, PHLEBOTOMINAE) IN CENTRAL ASIA: SPECIES COMPOSITION AND SPREAD]. AB - Based on the data available in the literature and the results of their investigations, the authors analyzed the spread of mosquitoes in Central Asia (Kazikhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan). It has been established that there are 27 mosquito species: P. papatasii, P. sergenti, P. caucasicus, P. mongolensis, P. andrejevi, P. alexandri, P. nuri, P. kandelakii, P. keshishiani, P. smirnovi, P. notus, P. wenioni, P. 1ongiductus, P. tuianicus, P. rupester, P. angustus, P. halepensis, P. zufagarensis, S. murgaitensis, S. dentata, S. pawlowsil, S. ciyda, S. pakistanica, S. sogdiana, S. sumbarica, S. grekovi, and G. dreyfussi turkestanica in this region. Five species of them (P. papatasii, P. sergenti, P. smirnovi, P. longiductus, and P. turanicus) are of medical importance. Maps of the spread of the species of medical importance have been compiled. Entomological observations should be made in individual areas of this region due to climate changes in the environment and to man-made interventions. PMID- 26827580 TI - [BLOODSUCKING MOSQUITOES (DIPTERA: CULICIDAE) IN, THE TULA REGION ARE POTENTIAL VECTORS OF DIROFILARIAS]. AB - Bloodsucking mosquitoes were collected in Tula and its Region in May to August 2013-2014. The fauna included 17 species from 5 genera in the subfamily Culicinae and Anopheles maculipennis complex in the subsystem Anophelinae. Ochlerotatus cantans was a dominant species in the collections. The dominant species also included Aedes einereus, Ae. vexans, Ae. geniculatus, Och. diantaeus, Och. intrudens, Och. Cataphylla, and Culex pipiens. The possible value of different mosquito species Dirofilaria repens and D. immitis as vectors of dirofilarasis was discussed. PMID- 26827581 TI - [MOTH FLIES (DIPTERA, PSYCHODIDAE) AS A NEW MEDICAL DISINSECTION OBJECT]. AB - This paper is dedicated to moth flies, a new medical disinsection object in our country. These insects are common in urban areas, generally in the premises with poor sanitary conditions. Moth fly larvae may cause accidental human urinary miasmata; imagoes, if many, become a worrisome factor; a source of allergy, and potential mechanical vectors of human diseases. In this connection, it is necessary to implement measures to control the number of the moth flies when the latter are detected on the objects particularly in therapeutic and preventive facilities and public catering esablishments. PMID- 26827582 TI - [ROLE OF ANIMALS AND HUMAN BEINGS IN THE SPREAD OF TRICHINOSIS IN THE KURSK REGION]. AB - Trichinosis is natural focal invasion in the Kursk Region. Porkworms (Trichinella) circulate in natural biocenoses among wild carnivorous mammals, wild boars, and rodents. Trichinosis cases are recorded in synanthropic animals. Carnivorous mammals form the basis for the parasitic system of trichinosis. The animals are infected with Trichinella through carnivorism, necrophagy, and cannibalism. The transport Trichinella vectors, necrophagous insects, naturally play an insignificant role-in the spread of trichinosis. Trichinella infection in animals occurs more commonly through necrophagia and cannibaism during winter months. Not only animals, but also man, play a great role in the spread of trichinosis. Infested wild and synanthropic aninals inhabiting the Kursk Region may carry the risk for Trichinella infection in the population. PMID- 26827583 TI - [The compounds MST-41 And MST-65. Preparation and investigation of its antihymenolepic activity]. PMID- 26827584 TI - [Preparation and antihymenolepic activity of the novel haloid- containing salicylanilide MST-63]. PMID- 26827586 TI - [THERAPEUTIC ACTIVITY OF MICRONIZED MEBENDAZOLE IN THE MUSCULAR PHASE OF EXPERIMENTAL TRICHINELLA SPIRALIS INVASION IN ALBINO MICE]. AB - The incidence of trichinosis in Russia was 0.07 per 100,000 population in 2014, which was 2.9-fold higher than that in 2013. Two WHO recommended medications mebendazole and albendazole are now used to treat humari trichinosis. The drugs are active against only mature helminths and non-encysted muscle larvae. The original oil suspension of micronized mebendazole was.found to have 100% efficacy against trichinosis in albino mice in the late muscular phase (encysted larvae) of hyperinvasion after intensive therapy under lifetime diagnostic guidance during and after a treatment cycle. The lifetime diagnostic method used to evaluate the larvicidal activity of anti-trichinosis agents in animals with experimental trichinosis revealed the signs of viaility, established a trend for deatih of Trichinella larvae, and determined their destructive changes. PMID- 26827585 TI - [EFFICACY OF A NEW MEBENDAZOLE FORMULATION FOR EXPERIMENTAL ECHINOCOCCUS GRANULOSUS LARVAL INVASION IN ALBINO MICE]. AB - The problem of echinococcosis has acquired special urgency in Russia in the last 10 years. The dramatically worse epidemiological situation of echinococcosis in the country is suggested by just frequent cases of cystic echinococcosis in the indigenous population of Moscow and its region, including children. Currently, albendazole that is less toxic than mebendazole remains the drug of choice, However, some authors note that E. granulosus larval cysts are moresusceptible to mebendazole than to albendazole. Both drugs mainly show parasitological activity and have no larvicidal effect particularly in larval alveococcosis. Analysis of the results of chemotherapy, with a group of benzimidazole carbamates for echinococcosis in 6 clinical centers from 5 European countries (Italy, Bulgaria, Romania, Greece, and Turkey) over the past 30 years showed that the evaluation of therapeutic effectiveness was overestimated; thus, 40% of all parasitic larval cysts that were considered dead became active again after, 2 years after the treatment. The original oil micronized mebendazole suspension tested by us in albino mice with late-stage larval cystic echinococcosis showed the properties of a highly effective and safe systemic larvicide that caused prompt death in the entire parasite population in the treated animals even in extreme hyperinvasion when the baseline parasite weight was greater than the host's one. PMID- 26827587 TI - [A LOCAL CASE OF CHRONIC STRONGYLOIDIASIS IN THE VOLGOGRAD REGION]. AB - The paper describes a case of disseminated strongyloidosis in a 52-year-old woman living in Volgograd. Filariform and. rhabditiform larvae of the nematode Strongyloides stercoralis were found when analyzing her urine, sputum, and feces. She had been followed up and treated for duodenal ulcer for more than 15 years. During that time, the patient periodically underwent radiographic and ultrasonic studies and clinical and biochemical blood tests. Fecal tests were not been carried out. This case could convince that there was a risk for human strongyloidosis in the arid region having a temperate climate in European Russia and when timely detection of invasion and specific treatment were not performed, there might be disseminated strongyloidosis. The reason for late diagnosis was epidemiological history (possible contact with soil) underestimation and improper patient examination. PMID- 26827588 TI - [VISCERAL LEISHMANIASIS IN A THREE-YEAR-OLD CHILD]. AB - The paper describes a clinical case of visceral leishmaniasis in a three-year-old child who Was born and is a permanent resident in Penm. Its clinical symptomatology; laboratory and instrumental findings; stages of a diagnostic search for fever of unknown origin concurrent with hepatosplenomegaly and pancytopenia; differential diagnosis with hemoblastosis; and an epidemiological history are detailed. Visceral leishmaniasis was diagnosed at examination of bone marrow specimens. The paper presents the positive results of combination etiopathogenetic treatment, which are confirmed by the time course of clinical changes and laboratory findings. PMID- 26827589 TI - [A PROJECT TARGETED APPROACH TO IMPROVING THE ENVIRONMENTAL TRAINING OF PARASITOLOGISTS]. AB - A project targeted approach is the methodological basis for organizing professional education, which deals with learning objectives, content, and technologies as a professional activity design where all components-of a teaching process are constructed on an integrative basis. The project targeted approach is the basis for a project method. The latter ensures that the learning objectives are achieved through the creation of a professionally significant problem, which should yield a real, tangible practical result. At the same time, the organization of a specialist's training and professional activities undergoes a complete cycle: from revelation of a problem to implementation of a project, its assessment and reflection (a comparative analysis of the organization and quality of practical activity). The high effectiveness of the project method contributes to the better environmental training of parasitologists and to the improvement of their professional readiness to solve specific parasitogenic problems. PMID- 26827590 TI - [EXPERIENCE IN TREATING HELMINTHISM WITH MICRONIZED ALBENDAZOLE (GELMODOL)]. AB - The paper gives the results of treatment with micronized albendazole (Gelmodol BM, World Medicine, UK) in 87 patients of the Department of Medical Parasitology and Tropical Diseases, Clinical and Diagnostic Center, Clinical Center, I.M.Sechenov First Moscow State Medical University. Thirty-two patients with echinococcosis 8 with alveococcosis (including 4 inoperable patients), 10 with ascariasis, 10 with toxocariasis, 15 with enterobiasis, and 12 people diagnosed with larva migrans were treated in 2013-2014. The drug's routine doses and dosage regimens were used. Albendazole (Gelmodol, World Medicine, UK) showed a high efficacy with good tolerability, which is highly competitive with that of the drugs manufactured by IPCA Laboratories Ltd., India (such as nemozole). Both medicaments above-mentioned may be successfully used in the treatment of many helminthisms. PMID- 26827591 TI - [Current methods and means to control Ixodidae ticks in natural biotopes]. PMID- 26827592 TI - [On the association between Blastocystis species and enteric microbiota in different macroorganism conditions]. PMID- 26827593 TI - [In memory of N.F. Darskaya]. PMID- 26827594 TI - [A Clinical Study of Acute Epiglottitis]. AB - We carried out a retrospective review of 285 cases of acute epiglottitis (180 males, 105 females, mean age 49.6 years) that required inpatients hospital care between 1998 and 2014. All the patients complained of sore throat, and 62 patients complained of respiratory discomfort; 17 patients had severe dyspnea, and 27 patients required airway management (tracheotomy in 25, cricothyroidotomy in 2 patients). All the patients survived. As acute epiglottitis can cause rapidly progressive airway obstruction and death, emergent airway management should be undertaken in patients with dyspnea. However, it is difficult to determine the indications for prophylactic respiratory management in patients without dyspnea. Therefore, the disease severity of the epiglottitis was evaluated on a five-grade scale according to the degree of swelling of both the epiglottis and the arytenoids. Although prospective evaluation is necessary, this scoring system may be beneficial to determine the indication for airway management, because all of the patients who complained of severe dyspnea or underwent airway management had grade 4 or 5 disease, while none of the patients with grade 1-3 disease required tracheotomy or cricothyroidotomy. Moreover, we compared the white blood cell count, body temperature, serum CRP and the interval from the onset between the group that required airway management and the group that did not require airway management. The white blood-cell count and body temperature were significantly higher, and the interval from the onset was significantly shorter in the group that required airway management than in the group that did not require airway management; however, the serum CRP level did not differ between the two groups. PMID- 26827595 TI - [Multicenter Clinical Study of Vibrant Soundbridge in Japan: Analysis of Subjective Questionnaires]. AB - The Vibrant Soundbridge (VSB) is an active middle ear implant with the Floating Mass Transducer (FMT). We performed a multicenter study to study the efficacy of the VSB by means of "the 10 Questionnaire on Hearing 2002" and "the APHAB questionnaire" at 13 hospitals between 2011 and 2013. In all, 23 patients with mixed or conductive hearing loss received VSB implantation by the round window placement technique. These individuals were generally unable to use, or gained little from conventional hearing aids or bone conduction hearing aids. Two questionnaires were administrated before the surgery and 20 weeks after the VSB implantation. Scores on every item of "the 10 Questionnaire on Hearing 2002" showed significant improvement under noise after VSB implantation. On the APHAB, the scores for Ease of Communication, Reverberation, and Background subscales improved significantly after the VSB implantation, while the score for the Aversiveness subscale alone failed to show a positive improvement from the inexperience to the new sound. Analysis of the responses to these subjective questionnaires revealed better results after VSB implantation as compared to the preoperative data. In conclusion, RW vibroplasty with the use of VSB provided subjective benefit in patients with conductive and mixed hearing loss. PMID- 26827596 TI - [Aural Stimulation with Capsaicin Ointment Improved the Swallowing Function in Patients with Dysphagia: Evaluation by the SMRC Scale]. AB - Cough and swallowing reflexes are important airway-protective mechanisms against aspiration. Angiotensin-converting enzyme (ACE) inhibitors, one of the side effects of which is cough, have been reported to reduce the incidence of aspiration pneumonia in hypertensive patients with stroke. ACE inhibitors have also been reported to improve the swallowing function in post-stroke patients. On the other hand, stimulation of the Arnold nerve, the auricular branch of the vagus, triggers the cough reflex (Arnold's ear-cough reflex). Capsaicin, an agonist of Transient Receptor Potential Vanilloid 1 (TRPV1), has been shown to activate the peripheral sensory C-fibers. Stimulation of the sensory branches of the vagus in the laryngotracheal mucosa with capsaicin induces the cough reflex and has been reported to improve the swallowing function in patients with dysphagia. In our previous study, we showed that aural stimulation of the Arnold nerve with 0.025% capsaicin ointment improved the swallowing function, as evaluated by the endoscopic swallowing score, in 26 patients with dysphagia. In the present study, the video images of swallowing recorded in the previous study were re-evaluated using the SMRC scale by an independent otolaryngologist who was blinded to the information about the patients and the endoscopic swallowing score. The SMRC scale is used to evaluate four aspects of the swallowing function: 1) Sensory: the initiation of the swallowing reflex as assessed by the white-out timing; 2) Motion: the ability to hold blue-dyed water in the oral cavity and induce laryngeal elevation; 3) Reflex: glottal closure and the cough reflex induced by touching the epiglottis or arytenoid with the endoscope; 4) Clearance: pharyngeal clearance of the blue-dyed water after swallowing. Accordingly, we demonstrated that a single application of capsaicin ointment to the external auditory canal of patients with dysphagia significantly improved the R, but not the S, M or C scores, and this effect lasted for 60 min. After repeated aural stimulation with the ointment for 7 days, the R score improved significantly in patients with severe dysphagia. The present findings suggest that stimulation of the Arnold's branch of the vagus in the external auditory canal with capsaicin improves the glottal closure and cough reflex in patients with dysphagia. Thus, aural stimulation with capsaicin represents a novel treatment for dysphagia. It is also suggested that repeated alternative aural stimulation with capsaicin for a week, rather than a single application, is needed to improve the swallowing function in patients with severe dysphagia. By the same mechanism as that underlying the effect of ACE inhibitors, aural stimulation with capsaicin may reduce the incidence of aspiration pneumonia in patients with dysphagia. PMID- 26827597 TI - [A Clinical Study of the Sclerotherapy for Large Venous Malformations of the Pharyngolarynx with Airway Stenosis]. AB - We treated four cases of airway stenosis associated with large venous malformations of the pharyngolarynx. The patients ranged in age from 33 to 53 years, and consisted of one male and three females. The venous malformation was located in the posterior wall of the oropharynx in two cases, in the hypopharynx in. one case, and in the anterior wall of the oropharynx in one case. All the patients complained of shortness of breath upon adopting the supine position. The patients were tracheotomized under general anesthesia and treated by sclerotherapy under videolaryngoscopic guidance. We used absolute ethanol, polidocanol or monoethanolamine oleate, as appropriate, depending on the case. In regard to the efficacy of the sclerotherapy, the venous malformation disappeared in one case and reduced in size in the remaining three cases, and no severe adverse events were recognized in any of the cases. All the patients were discharged from the hospital within two weeks and did not need tracheostomy. Sclerotherapy umder videolaryngoscopic guidance is effective for the treatment of large venous malformations in the pharyngolarynx. PMID- 26827600 TI - High-Performance Affinity Chromatography: Applications in Drug-Protein Binding Studies and Personalized Medicine. AB - The binding of drugs with proteins and other agents in serum is of interest in personalized medicine because this process can affect the dosage and action of drugs. The extent of this binding may also vary with a given disease state. These interactions may involve serum proteins, such as human serum albumin or alpha1 acid glycoprotein, or other agents, such as lipoproteins. High-performance affinity chromatography (HPAC) is a tool that has received increasing interest as a means for studying these interactions. This review discusses the general principles of HPAC and the various approaches that have been used in this technique to examine drug-protein binding and in work related to personalized medicine. These approaches include frontal analysis and zonal elution, as well as peak decay analysis, ultrafast affinity extraction, and chromatographic immunoassays. The operation of each method is described and examples of applications for these techniques are provided. The type of information that can be obtained by these methods is also discussed, as related to the analysis of drug-protein binding and the study of clinical or pharmaceutical samples. PMID- 26827601 TI - Role of Proteomics in the Development of Personalized Medicine. AB - Advances in proteomic technologies have made import contribution to the development of personalized medicine by facilitating detection of protein biomarkers, proteomics-based molecular diagnostics, as well as protein biochips and pharmacoproteomics. Application of nanobiotechnology in proteomics, nanoproteomics, has further enhanced applications in personalized medicine. Proteomics-based molecular diagnostics will have an important role in the diagnosis of certain conditions and understanding the pathomechanism of disease. Proteomics will be a good bridge between diagnostics and therapeutics; the integration of these will be important for advancing personalized medicine. Use of proteomic biomarkers and combination of pharmacoproteomics with pharmacogenomics will enable stratification of clinical trials and improve monitoring of patients for development of personalized therapies. Proteomics is an important component of several interacting technologies used for development of personalized medicine, which is depicted graphically. Finally, cancer is a good example of applications of proteomic technologies for personalized management of cancer. PMID- 26827602 TI - Metabolomics and Personalized Medicine. AB - Current clinical practice strongly relies on the prognosis, diagnosis, and treatment of diseases using methods determined and averaged for the specific diseased cohort/population. Although this approach complies positively with most patients, misdiagnosis, treatment failure, relapse, and adverse drug effects are common occurrences in many individuals, which subsequently hamper the control and eradication of a number of diseases. These incidences can be explained by individual variation in the genome, transcriptome, proteome, and metabolome of a patient. Various "omics" approaches have investigated the influence of these factors on a molecular level, with the intention of developing personalized approaches to disease diagnosis and treatment. Metabolomics, the newest addition to the "omics" domain and the closest to the observed phenotype, reflects changes occurring at all molecular levels, as well as influences resulting from other internal and external factors. By comparing the metabolite profiles of two or more disease phenotypes, metabolomics can be applied to identify biomarkers related to the perturbation being investigated. These biomarkers can, in turn, be used to develop personalized prognostic, diagnostic, and treatment approaches, and can also be applied to the monitoring of disease progression, treatment efficacy, predisposition to drug-related side effects, and potential relapse. In this review, we discuss the contributions that metabolomics has made, and can potentially still make, towards the field of personalized medicine. PMID- 26827603 TI - Clinical Perspectives on Targeting Therapies for Personalized Medicine. AB - Expected benefits from new technology include more efficient patient selection for clinical trials, more cost-effective treatment pathways for patients and health services and a more profitable accelerated approach for drug developers. Regulatory authorities expect the pharmaceutical and biotechnology industries to accelerate their development of companion diagnostics and companion therapeutics toward the goal of safer and more effective personalized medicine, and expect health services to fund and prescribers to adopt these new therapeutic technologies. This review discusses the importance of a range of new approaches to developing new and reprofiled medicines to treat common and serious diseases, and rare diseases: new network pharmacology approaches, adaptive trial designs with enriched populations more likely to respond safely to treatment, as assessed by companion diagnostics for response and toxicity risk and use of "real world" data. Case studies are described of single and multiple protein drug targets in several important therapeutic areas. These case studies also illustrate the value and complexity of use of selective biomarkers of clinical response and risk of adverse drug effects, either singly or in combination. PMID- 26827604 TI - Personalized Medicine in Respiratory Disease: Role of Proteomics. AB - Respiratory diseases affect humanity globally, with chronic lung diseases (e.g., asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, among others) and lung cancer causing extensive morbidity and mortality. These conditions are highly heterogeneous and require an early diagnosis. However, initial symptoms are nonspecific, and the clinical diagnosis is made late frequently. Over the last few years, personalized medicine has emerged as a medical care approach that uses novel technology aiming to personalize treatments according to the particular patient's medical needs. This review highlights the contributions of proteomics toward the understanding of personalized medicine in respiratory disease and its potential applications in the clinic. PMID- 26827605 TI - Computational Approaches to Accelerating Novel Medicine and Better Patient Care from Bedside to Benchtop. AB - Some successes have been achieved in the war on cancer over the past 30 years with recent efforts on protein kinase inhibitors. Nonetheless, we are still facing challenges due to cancer evolution. Cancers are complex and heterogeneous due to primary and secondary mutations, with phenotypic and molecular heterogeneity manifested among patients of a cancer, and within an individual patient throughout the disease course. Our understanding of cancer genomes has been facilitated by advances in omics and in bioinformatics technologies; major areas in cancer research are advancing in parallel on many fronts. Computational methods have been developed to decipher the molecular complexity of cancer and to identify driver mutations in cancers. Utilizing the identified driver mutations to develop effective therapy would require biological linkages from cellular context to clinical implication; for this purpose, computational mining of biomedical literature facilitates utilization of a huge volume of biomedical research data and knowledge. In addition, frontier technologies, such as genome editing technologies, are facilitating investigation of cancer mutations, and opening the door for developing novel treatments to treat diseases. We will review and highlight the challenges of treating cancers, which behave like moving targets due to mutation and evolution, and the current state-of-the-art research in the areas mentioned above. PMID- 26827606 TI - Molecular Dynamics: New Frontier in Personalized Medicine. AB - The field of drug discovery has witnessed infinite development over the last decade with the demand for discovery of novel efficient lead compounds. Although the development of novel compounds in this field has seen large failure, a breakthrough in this area might be the establishment of personalized medicine. The trend of personalized medicine has shown stupendous growth being a hot topic after the successful completion of Human Genome Project and 1000 genomes pilot project. Genomic variant such as SNPs play a vital role with respect to inter individual's disease susceptibility and drug response. Hence, identification of such genetic variants has to be performed before administration of a drug. This process requires high-end techniques to understand the complexity of the molecules which might bring an insight to understand the compounds at their molecular level. To sustenance this, field of bioinformatics plays a crucial role in revealing the molecular mechanism of the mutation and thereby designing a drug for an individual in fast and affordable manner. High-end computational methods, such as molecular dynamics (MD) simulation has proved to be a constitutive approach to detecting the minor changes associated with an SNP for better understanding of the structural and functional relationship. The parameters used in molecular dynamic simulation elucidate different properties of a macromolecule, such as protein stability and flexibility. MD along with docking analysis can reveal the synergetic effect of an SNP in protein-ligand interaction and provides a foundation for designing a particular drug molecule for an individual. This compelling application of computational power and the advent of other technologies have paved a promising way toward personalized medicine. In this in-depth review, we tried to highlight the different wings of MD toward personalized medicine. PMID- 26827607 TI - Personalized Pharmacoperones for Lysosomal Storage Disorder: Approach for Next Generation Treatment. AB - Lysosomal storage disorders (LSDs) are a collection of inborn errors of metabolic disorders affected by mutations in lysosome functional genes, commonly acid hydrolases. From the past decades, many approaches like enzyme replacement therapy, substrate reduction therapy are followed to treat these conditions. However, all these approaches have their own limitations. Proof-of-concept studies on pharmacological chaperone therapy (PCT) is now transformed into clinical practice to treat LSDs. Furthermore, it is narrowed with individuals to chaperone sensitive, specific mutations. Hence, personalizing the PCT will be a new direction to combat LSDs. In this review, we have discussed the available clinical strategies and pointed the light on how pharmacological chaperones can be personalized and hopeful to be a next-generation approach to address LSDs. PMID- 26827608 TI - Investigating the Inhibitory Effect of Wortmannin in the Hotspot Mutation at Codon 1047 of PIK3CA Kinase Domain: A Molecular Docking and Molecular Dynamics Approach. AB - Oncogenic mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) are the most frequently reported in association with various forms of cancer. Several studies have reported the significance of hotspot mutations in a catalytic subunit of PIK3CA in association with breast cancer. Mutations are frequently observed in the highly conserved region of the kinase domain (797-1068 amino acids) of PIK3CA are activating or gain-of-function mutations. Mutation in codon 1047 occurs in the C-terminal region of the kinase domain with histidine (H) replaced by arginine (R), lysine (L), and tyrosine (Y). Pathogenicity and protein stability predictors PhD-SNP, Align GVGD, HANSA, iStable, and MUpro classified H1047R as highly deleterious when compared to H1047L and H1047Y. To explore the inhibitory activity of Wortmannin toward PIK3CA, the three-dimensional structure of the mutant protein was determined using homology modeling followed by molecular docking and molecular dynamics analysis. Docking studies were performed for the three mutants and native with Wortmannin to measure the differences in their binding pattern. Comparative docking study revealed that H1047R-Wortmannin complex has a higher number of hydrogen bonds as well as the best binding affinity next to the native protein. Furthermore, 100 ns molecular dynamics simulation was initiated with the docked complexes to understand the various changes induced by the mutation. Though Wortmannin was found to nullify the effect of H1047R over the protein, further studies are required for designing a better compound. As SNPs are major genetic variations observed in disease condition, personalized medicine would provide enhanced drug therapy. PMID- 26827609 TI - Role of von Willebrand Factor--A1 Domain Variants P1266L, H1268D, C1272R, and C1272F in VWD: A Molecular Modeling and Simulation Analysis Approach. AB - von Willebrand disease (VWD) is an autosomal inherited disorder related to trauma related bleeding in affected people. VWD results from deficiency of von Willebrand factor (VWF)--a glycoprotein involved in hemostasis and carrier for factor VIII (FVIII). Mutations in A1 domain of von Willebrand factor (VWD) gene are exceptionally polymorphic and associated with adhesion movement, clearance, and binding properties that could be interfaced with thrombosis. To address this issue, we implemented in silico prediction algorithms, namely, SIFT, PolyPhen 2.0, I-Mutant 3.0, SNAP, Align GVGD, PhD-SNP, SNPs&GO, and MutPred to classify the variants as pathogenic and affecting protein stability. Based on prediction scores, four variants, namely, P1266L, H1268D, C1272R, and C1272F, were predicted as highly deleterious from a pool of 72 nsSNPs/variants in A1 domain of VWD belonging to type 2A and 2B. Upon literature survey, amino acid substitution (P > L) at position 1266 is involved in improving the connection with platelets, substitution (C -> F) at position 1272 results in extreme bleeding in patients, and substitution (H -> D) at position 1268 disturbs the salt bridge scaffold were considered for further analysis. Through molecular dynamic simulation analysis over a period of 100 ns showed that four mutations near N-terminal region bring about a change in structure and function of the native VWD protein. PMID- 26827610 TI - Preface. PMID- 26827611 TI - Enantioselective Synthesis of alpha-Amino Phosphonates via Pd-Catalyzed Asymmetric Hydrogenation. AB - A highly enantioselective palladium-catalyzed hydrogenation of a series of linear and cyclic alpha-iminophosphonates has been achieved, providing efficient access to optically active alpha-aminophosphonates with up to 99% ee. PMID- 26827612 TI - Factors associated with colorectal cancer occurrence after colonoscopy that did not diagnose colorectal cancer. AB - BACKGROUND AND AIMS: Up to 6% of colorectal cancers (CRCs) are diagnosed within 5 years of a colonoscopy that did not diagnose CRC (post-colonoscopy colorectal cancer, PCCRC). PCCRC and associated risk factors were examined within a national hospital episode database. METHODS: A retrospective case-control study of all colonoscopies performed on adults recorded in Hospital Episode Statistics (HES) between 2003 and 2009 in England. PCCRC cases underwent colonoscopy 6 to 60 months before diagnosis; controls had not undergone colonoscopy 6 to 60 months before diagnosis. Multivariate logistic regression analysis examined associations with PCCRC. RESULTS: A total of 1,439,684 colonoscopies were analyzed, including 67,202 cases of CRC and 8147 cases of PCCRC (12.1%). Multivariate analysis revealed that female sex (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.08-1.19; P < .001), older age (70-74 years) (OR, 1.09; 95% CI, 1.00-1.18; P = .039), increased comorbidity (Charlson index 5+) (OR, 1.16; 95% CI, 1.05-1.28; P < .003), and CRC of the right side of the colon (OR, 1.17; 95% CI, 1.11-1.23; P < .0001) were associated with PCCRC. Emergency colonoscopy (OR, 0.54; 95% CI, 0.59 0.69; P < .0001) was negatively associated with PCCRC. More individuals with PCCRC developed metastases within 12 months and fewer underwent surgery (OR, 0.33; 95% CI, 0.32-0.35; P < .0001) or chemotherapy (OR, 0.66; 95% CI, 0.62 0.69), P < .0001). PCCRC rates varied 2-fold between providers and PCCRC was associated with medium-volume providers compared with high-volume providers (OR, 1.13; 95% CI, 1.01-1.27; P = .035). The PCCRC rate fell from 13.8% in 2003 to 11.9% in 2009. CONCLUSIONS: PCCRC occurred in 12.1% of patients with CRC between 2003 and 2009. PCCRC was associated with female sex, older age, increased comorbidity, CRC of the right side of the colon, elective procedures, and colonoscopy volume. PCCRC was associated with worse outcomes. PMID- 26827613 TI - The influence of ultrasound measurement techniques on the age-related differences in Achilles tendon size. AB - Achilles tendon (AT) properties change with age, however the extent to which aging influences the size of the AT may be influenced by the measurement technique. The purpose of this study was to 1) examine the age-related differences in AT size using measures of cross-sectional area (CSA) and thickness, and 2) to determine the test-retest reliability and minimum difference (MD) values of these measures. The size of the AT was examined in 19 young (19.79 +/- 2.3 years) and 18 older (69.4 +/- 3.1 years) healthy men on two separate occasions using an ultrasonography. The CSA and thickness of the AT were determined by separate transverse and longitudinal scans on the right leg at the same distance from the medial malleolus, respectively. Prior to and after accounting for body mass, AT CSA was larger (P <= 0.01) in the older men (64.49 +/- 13.87 mm(2)) when compared to the younger men (44.12 +/- 16.04 mm(2)), however there were no differences in AT thickness between age groups (P=0.96). In addition, there was no systematic error (P>0.05) between testing days, and the intraclass correlation coefficients, standard error of measurement (expressed as a % of the mean), and MD values for CSA and thickness ranged from 0.80-0.98, 5.46 8.68%, and 5.65-7.94 mm(2) and 0.51-0.86 mm, respectively between both groups. These findings suggest that the reliability of the CSA and thickness measurements were similar, however, CSA was a more sensitive measure to detect the age-related changes of AT size. PMID- 26827614 TI - The relationship between alcohol consumption and related harm among young university students. AB - Issue addressed Research has shown that Australian university students consume alcohol at a higher level than their peers from the general population and are therefore more likely to witness and experience alcohol-related harm. This study measured the prevalence of alcohol consumption among 18-24-year-old university students and the association between alcohol consumption and witnessed and experienced harms. Methods A random cross-sectional sample of university students aged 18-24 years (n=2466) was recruited via the University Survey Office and through random intercept at campus market day. All participants completed an online survey that included the Alcohol Use Disorders Identification Test, Alcohol Problems Scale and an additional scale measuring witnessed harm. Results Principal Components Analysis revealed three factors within the Alcohol Problems Scale; i.e. Criminal and Aggressive Behaviour, Health and Emotional Harms and Sexual Harms. Students who consume alcohol at high-risk levels were significantly more likely to score highly on each factor, 1.6 times more likely to experience harm and 1.1 times more likely to witness harm than students who consume alcohol at low-risk levels. Conclusions The positive association between alcohol consumption and alcohol-related harm supports previous findings. This study adds previous research through the categorisation of harm into factors. So what? Integrated and comprehensive interventions addressing alcohol consumption among young university students that are informed by evidence-based research can be tailored to ensure that they meet the needs of the target group. PMID- 26827615 TI - Do apprehended saffron finches know how to survive predators? A careful look at reintroduction candidates. AB - Wildlife trafficking is a major factor contributing to the reduction of biological diversity. In Brazil, trafficked animals are apprehended by environmental agencies and released in the wild. The maintenance of wild animals in captivity may jeopardize their survival in the wild, for example, by reducing their ability to recognize a predator. Saffron finches (Sicalis flaveola) are among the most trafficked Brazilian birds. Twenty-eight apprehended saffron finches were submitted to Temperament and Predator-recognition tests, with presentation of predator and non-predator models: a live and a taxidermised hawk, a taxidermised armadillo and a Lego cube. The captive saffron finches have retained general anti-predator responses, such as increasing alertness, avoiding back-facing and keeping distance when presented with potential predators. The birds responded more strongly to the live hawk than to the cube. Although some responses to the other stimuli were not statistically different from each other, a decrease in intensity of response with the decrease in threat level was remarkable. We found no relationship between temperament traits and responses to predators: a possible consequence of husbandry practices in captivity. Our results indicate saffron finches may retain basic anti-predator responses in captivity, which favours release and reintroduction programmes: information relevant for conservation management. PMID- 26827616 TI - Dose-response association of physical activity with HbA1c: Intensity and bout length. AB - OBJECTIVE: The aims of this study were to characterize the dose-response relationship between moderate-to-vigorous intensity physical activity (MVPA), and light-intensity activity with HbA1c in adults at low, moderate, and high risks of type 2 diabetes, and to compare the relationship of short (1 to 9min) versus long (10+min) bouts of MVPA with HbA1c. METHODS: Data from 2707 participants from the 2003-2006 National Health And Nutrition Examination Survey were analyzed in 2014 2015. Type 2 diabetes risk was classified into three groups based upon age (<40years; >=40years) and BMI (<30; >=30). The relationship between HbA1c and accelerometer-based physical activity variables was assessed using multiple regression models. RESULTS: There was a curvilinear dose-response relationship between HbA1c with total activity and MVPA in adults at moderate or high risk for type 2 diabetes: higher amounts of physical activity were associated with lower HbA1c. The association of physical activity on HbA1c was stronger at lower levels of physical activity. There was no dose-response relationship in adults at low risk for type 2 diabetes. The relationship between short bouts with HbA1c was stronger than for bouts>=10min. CONCLUSIONS: In adults at risk for type 2 diabetes, there is a dose-response relationship between physical activity and HbA1c levels such that the relationship: (1) is curvilinear; (2) is stronger when a higher percent of total activity comes from MVPA; and (3) is more potent with short bouts of MVPA. Fractionalized physical activity of at least moderate intensity may contribute to long-term glucose control. PMID- 26827618 TI - Price promotions for food and beverage products in a nationwide sample of food stores. AB - Food and beverage price promotions may be potential targets for public health initiatives but have not been well documented. We assessed prevalence and patterns of price promotions for food and beverage products in a nationwide sample of food stores by store type, product package size, and product healthfulness. We also assessed associations of price promotions with community characteristics and product prices. In-store data collected in 2010-2012 from 8959 food stores in 468 communities spanning 46 U.S. states were used. Differences in the prevalence of price promotions were tested across stores types, product varieties, and product package sizes. Multivariable regression analyses examined associations of presence of price promotions with community racial/ethnic and socioeconomic characteristics and with product prices. The prevalence of price promotions across all 44 products sampled was, on average, 13.4% in supermarkets (ranging from 9.1% for fresh fruits and vegetables to 18.2% for sugar-sweetened beverages), 4.5% in grocery stores (ranging from 2.5% for milk to 6.6% for breads and cereals), and 2.6% in limited service stores (ranging from 1.2% for fresh fruits and vegetables to 4.1% for breads and cereals). No differences were observed by community characteristics. Less-healthy versus more healthy product varieties and larger versus smaller product package sizes generally had a higher prevalence of price promotion, particularly in supermarkets. On average, in supermarkets, price promotions were associated with 15.2% lower prices. The observed patterns of price promotions warrant more attention in public health food environment research and intervention. PMID- 26827619 TI - Evolution of Strigolactone Perception by Seeds of Parasitic Plants: Reinventing the Wheel. PMID- 26827620 TI - Honeycomb-shaped surface topography induces differentiation of human mesenchymal stem cells (hMSCs): uniform porous polymer scaffolds prepared by the breath figure technique. AB - Polystyrene honeycomb scaffolds with different pore sizes were successfully fabricated by casting a polymer solution under humid conditions in order to investigate the effect of porous microtopography on hMSC differentiation. We have used honeycomb scaffolds to achieve the microtopography-induced differentiation of hMSCs. Honeycomb scaffolds led hMSCs to osteospecific and myospecific differentiations depending on the size of pores. This selective differentiation suggested that surface microtopography alone may be effective for using hMSCs in regenerative medicine and tissue engineering. PMID- 26827617 TI - Social norms and financial incentives to promote employees' healthy food choices: A randomized controlled trial. AB - OBJECTIVE: Population-level strategies to improve healthy food choices are needed for obesity prevention. We conducted a randomized controlled trial of 2672 employees at the Massachusetts General Hospital who were regular customers of the hospital cafeteria with all items labeled green (healthy), yellow (less healthy), or red (unhealthy) to determine if social norm (peer-comparison) feedback with or without financial incentives increased employees' healthy food choices. METHODS: Participants were randomized in 2012 to three arms: 1) monthly letter with social norm feedback about healthy food purchases, comparing employee to "all" and to "healthiest" customers (feedback-only); 2) monthly letter with social norm feedback plus small financial incentive for increasing green purchases (feedback incentive); or 3) no contact (control). The main outcome was change in proportion of green-labeled purchases at the end of 3-month intervention. Post-hoc analyses examined linear trends. RESULTS: At baseline, the proportion of green-labeled purchases (50%) did not differ between arms. At the end of the 3-month intervention, the percentage increase in green-labeled purchases was larger in the feedback-incentive arm compared to control (2.2% vs. 0.1%, P=0.03), but the two intervention arms were not different. The rate of increase in green-labeled purchases was higher in both feedback-only (P=0.04) and feedback-incentive arms (P=0.004) compared to control. At the end of a 3-month wash-out, there were no differences between control and intervention arms. CONCLUSIONS: Social norms plus small financial incentives increased employees' healthy food choices over the short-term. Future research will be needed to assess the impact of this relatively low-cost intervention on employees' food choices and weight over the long-term. TRIAL REGISTRATION: Clinical Trials.gov: NCT01604499. PMID- 26827621 TI - Analyzing health insurance claims on different timescales to predict days in hospital. AB - Health insurers maintain large databases containing information on medical services utilized by claimants, often spanning several healthcare services and providers. Proper use of these databases could facilitate better clinical and administrative decisions. In these data sets, there exists many unequally spaced events, such as hospital visits. However, data mining of temporal data and point processes is still a developing research area and extracting useful information from such data series is a challenging task. In this paper, we developed a time series data mining approach to predict the number of days in hospital in the coming year for individuals from a general insured population based on their insurance claim data. In the proposed method, the data were windowed at four different timescales (bi-monthly, quarterly, half-yearly and yearly) to construct regularly spaced time series features extracted from such events, resulting in four associated prediction models. A comparison of these models indicates models using a half-yearly windowing scheme delivers the best performance on all three populations (the whole population, a senior sub-population and a non-senior sub population). The superiority of the half-yearly model was found to be particularly pronounced in the senior sub-population. A bagged decision tree approach was able to predict 'no hospitalization' versus 'at least one day in hospital' with a Matthews correlation coefficient (MCC) of 0.426. This was significantly better than the corresponding yearly model, which achieved 0.375 for this group of customers. Further reducing the length of the analysis windows to three or two months did not produce further improvements. PMID- 26827622 TI - A knowledgebase of the human Alu repetitive elements. AB - Alu elements are the most abundant retrotransposons in the human genome with more than one million copies. Alu repeats have been reported to participate in multiple processes related with genome regulation and compartmentalization. Moreover, they have been involved in the facilitation of pathological mutations in many diseases, including cancer. The contribution of Alus and other repeats in genomic regulation is often overlooked because their study poses technical and analytical challenges hardly attainable with conventional strategies. Here we propose the integration of ontology-based semantic methods to query a knowledgebase for the human Alus. The knowledgebase for the human Alus leverages Sequence (SO) and Gene Ontologies (GO) and is devoted to address functional and genetic information in the genomic context of the Alus. For each Alu element, the closest gene and transcript are stored, as well their functional annotation according to GO, the state of the chromatin and the transcription factors binding sites inside the Alu. The model uses Web Ontology Language (OWL) and Semantic Web Rule Language (SWRL). As a case of use and to illustrate the utility of the tool, we have evaluated the epigenetic states of Alu repeats associated with gene promoters according to their transcriptional activity. The ontology is easily extendable, offering a scaffold for the inclusion of new experimental data. The RDF/XML formalization is freely available at http://aluontology.sourceforge.net/. PMID- 26827623 TI - IRB reliance: An informatics approach. AB - Multi-site Institutional Review Board (IRB) review of clinical research projects is an important but complex and time-consuming activity that is hampered by disparate non-interoperable computer systems for management of IRB applications. This paper describes our work toward harmonizing the workflow and data model of IRB applications through the development of a software-as-a-service shared-IRB platform for five institutions in South Carolina. Several commonalities and differences were recognized across institutions and a core data model that included the data elements necessary for IRB applications across all institutions was identified. We extended and modified the system to support collaborative reviews of IRB proposals within routine workflows of participating IRBs. Overall about 80% of IRB application content was harmonized across all institutions, establishing the foundation for a streamlined cooperative review and reliance. Since going live in 2011, 49 applications that underwent cooperative reviews over a three year period were approved, with the majority involving 2 out of 5 institutions. We believe this effort will inform future work on a common IRB data model that will allow interoperability through a federated approach for sharing IRB reviews and decisions with the goal of promoting reliance across institutions in the translational research community at large. PMID- 26827624 TI - Generating a robust statistical causal structure over 13 cardiovascular disease risk factors using genomics data. AB - Understanding causal relationships among large numbers of variables is a fundamental goal of biomedical sciences and can be facilitated by Directed Acyclic Graphs (DAGs) where directed edges between nodes represent the influence of components of the system on each other. In an observational setting, some of the directions are often unidentifiable because of Markov equivalency. Additional exogenous information, such as expert knowledge or genotype data can help establish directionality among the endogenous variables. In this study, we use the method of principle component analysis to extract information across the genome in order to generate a robust statistical causal network among phenotypes, the variables of primary interest. The method is applied to 590,020 SNP genotypes measured on 1596 individuals to generate the statistical causal network of 13 cardiovascular disease risk factor phenotypes. First, principal component analysis was used to capture information across the genome. The principal components were then used to identify a robust causal network structure, GDAG, among the phenotypes. Analyzing a robust causal network over risk factors reveals the flow of information in direct and alternative paths, as well as determining predictors and good targets for intervention. For example, the analysis identified BMI as influencing multiple other risk factor phenotypes and a good target for intervention to lower disease risk. PMID- 26827626 TI - Magnocellular hypothalamic system and its interaction with the hypothalamo pituitary-adrenal axis. AB - The hypothalamo-neurohypophyseal system plays a key role in maintaining homeostasis and in regulation of numerous adaptive reactions, e.g., endocrine stress response. Nonapeptides vasopressin and oxytocin are the major hormones of this system. They are synthesized by magnocellular neurons of the paraventricular and supraoptic hypothalamic nuclei. Magnocellular vasopressin is known to be one of the main physiological regulators of water-electrolyte balance. Its importance for control of the hypothalamo-pituitary-adrenal axis has been widely described. Magnocellular oxytocin is secreted predominantly during lactation and parturition. The complex actions of oxytocin within the brain include control of reproductive behavior and its involvement in central stress response to different stimuli. It's neuroendocrine basis is activation of the hypothalamo-pituitary adrenal axis: corticotropin-releasing hormone is synthesized in parvocellular neurons of the paraventricular hypothalamic nuclei. The transitory coexpression of vasopressin in these cells upon stress has been described. Glucocorticoids, the end products of the hypothalamo-pituitary-adrenal axis have both central and peripheral actions. Their availability to target tissues is mainly dependent on systemic levels of corticosteroid-binding globulin. Intrinsic expression of this protein in different brain regions in neurons and glial cells has been recently demonstrated. Regulation of the hypothalamo-pituitary-adrenal axis and hypothalamo-neurohypophyseal system is highly complex. The role of both systems in the pathogenesis of various chronic ailments in humans has extensively been studied. Their disturbed functioning seems to be linked to various psychiatric, autoimmune and cardiovascular pathologies. PMID- 26827625 TI - Single body parts are processed by individual neurons in the mouse dorsolateral striatum. AB - Interest in the dorsolateral striatum (DLS) has generated numerous scientific studies of its neuropathologies, as well as its roles in normal sensorimotor integration and learning. Studies are informed by knowledge of DLS functional organization, the guiding principle being its somatotopic afferent projections from primary somatosensory (S1) and motor (M1) cortices. The potential to connect behaviorally relevant function to detailed structure is elevated by mouse models, which have access to extensive genetic neuroscience tool kits. Remaining to be demonstrated, however, is whether the correspondence between S1/M1 corticostriatal terminal distributions and the physiological properties of DLS neurons demonstrated in rats and non-human primates exists in mice. Given that the terminal distribution of S1/M1 projections to the DLS in mice is similar to that in rats, we studied whether firing rates (FRs) of DLS neurons in awake, behaving mice are related to activity of individual body parts. MSNs exhibited robust, selective increases in FR during movement or somatosensory stimulation of single body parts. Properties of MSNs, including baseline FRs, locations, responsiveness to stimulation, and proportions of responsive neurons were similar to properties observed in rats. Future studies can be informed by the present demonstration that the mouse lateral striatum functions as a somatic sensorimotor sector of the striatum and appears to be a homolog of the primate putamen, as demonstrated in rats (Carelli and West, 1991). PMID- 26827627 TI - Identification of five novel STAR variants in ten Chinese patients with congenital lipoid adrenal hyperplasia. AB - Congenital lipoid adrenal hyperplasia (CLAH) is a rare autosomal recessive disorder caused by defective synthesis of all steroids. This disorder is characterized by 46,XY sex reversal, skin hyperpigmentation, early-onset adrenal crisis and enlarged adrenal with fatty accumulation. CLAH is caused by mutations in the STAR gene. The clinical features and STAR gene mutation spectrum of a large cohort of Chinese patients with CLAH were not reported previously. We performed clinical retrospective review and genetic analysis of the STAR gene in ten unrelated Chinese phenotypic female patients who were clinically diagnosed with CLAH and followed up in our hospital from 2006 to 2015. All ten patients, including two 46,XY females and eight 46,XX females, presented skin hyperpigmentation and early salt-wasting episode, and showed normal growth and development after steroid replacement treatment. Totally 20 mutant alleles containing 11 different STAR gene mutations were identified in these ten patients, including five novel variants (two missense and three null variants), all predicted to be pathogenic in bioinformatics analysis, and six mutations described in previous literature. Among these 11 mutations, a reported mutation c.772C>T and a novel variant c.707_708delinsCTT were most frequent, accounting for 35% and 15% of the total mutant alleles, respectively. This is the first report of a large Chinese cohort with CLAH, presenting the mutation spectrum of the STAR gene and two possible founder mutations in the Chinese population, which may contribute to better genetic counseling and prenatal diagnosis. PMID- 26827629 TI - Synthesis and antifungal activity of bile acid-derived oxazoles. AB - Peracetylated bile acids (1a-g) were used as starting materials for the preparation of fourteen new derivatives bearing an oxazole moiety in their side chain (6a-g, 8a-g). The key step for the synthetic path was a Dakin-West reaction followed by a Robinson-Gabriel cyclodehydration. A simpler model oxazole (12) was also synthesized. The antifungal activity of the new compounds (6a-g) as well as their starting bile acids (1a-g) was tested against Candida albicans. Compounds 6e and 6g showed the highest percentages of inhibition (63.84% and 61.40% at 250 MUg/mL respectively). Deacetylation of compounds 6a-g, led to compounds 8a-g which showed lower activities than the acetylated derivatives. PMID- 26827628 TI - Synthesis and biological evaluation of bufalin-3-yl nitrogen-containing-carbamate derivatives as anticancer agents. AB - A series of bufalin-3-yl nitrogen-containing-carbamate derivatives 3 were designed, synthesized, and evaluated for their proliferation inhibition activities against human cervical epithelial adenocarcinoma (HeLa) cell line. The structure-activity relationships (SARs) of this new series are described in this paper. Cytotoxicity data revealed that the C3 moiety had an important influence on cytotoxic activity. Compound 3i-HCl exhibited significant in vitro antiproliferative activity against the ten tested tumor cell lines, with IC50 values ranging from 0.30 to 1.09 nM. Furthermore, 3i-HCl can significantly inhibit tumor growth by 100% at the dose 2 mg/kg by iv, or 4 mg/kg by ig. PMID- 26827630 TI - Catalytic cyclometallation in steroid chemistry IV: Efficient method for the synthesis of tetrahydrothiophene, tetrahydroselenophen and cyclopentanone derivatives of (5alpha)-cholestane. AB - Catalytic cycloalumination of (3beta,5alpha)-3-vinylcholestane and (3alpha,5alpha)-3-allylcholestane with Et3Al catalyzed by Cp2ZrCl2 was performed for the first time to give previously unknown aluminacyclopentanes in ~90% yield; these products were converted in situ to carbo- and heterocyclic (5alpha) cholestane derivatives. PMID- 26827631 TI - The -94Ins/DelATTG polymorphism in NFkappaB1 promoter modulates chronic hepatitis C and liver disease progression. AB - Infection with Hepatitis C Virus (HCV) is one of the most important risk factor of hepatocellular carcinoma (HCC). HCV is suspected to induce HCC primarily through chronic inflammation and promotion of cirrhosis, a well-known pre neoplastic condition. The NF-kappaB pathway is a key regulator of immune and inflammatory processes and plays a pivotal role in oncogenesis. Genetic variations affecting the pathway may alter NF-kappaB activity in response to HCV infection and contribute to liver tumorigenesis. The present study aims to evaluate the association between -94Ins/DelATTG (rs28362491) polymorphism in NF kappaB1 gene promoter region and 2758G>A (rs696) single nucleotide polymorphism in the 3'UTR region of NFkappaBIA and the outcomes of HCV infection. In this case control study, 559 subjects (343 patients with HCV infection including 237 mild chronic hepatitis patients and 106 patients with Advanced Liver Disease (AdLD), 78 individuals who naturally cleared HCV and 138 healthy subjects) were genotyped for the NFkappaB1 and NFkappaBIA SNPs using PCR-RFLP. Logistic regression was used to assess the association between polymorphisms and the outcome and progression of the infection. Variation at rs696 was not associated with HCV resolution or progression (P>0.05). By contrast, the Ins/Ins genotype was associated with a 4-fold increase of AdLD risk when compared to mild chronic hepatitis C (OR=4.69; 95% CI, 2.15-10.19; P=0.0001) and the risk was more pronounced when compared to healthy controls (OR=5.02; 95% CI, 2.30-10.98; P=0.00005). Furthermore, carriage of Ins allele at rs28362491 was significantly associated with higher viral loads (P=0.003). Our results suggest that variation in NFkappaB1 gene promoter modulates the progression of chronic hepatitis C toward advanced liver disease. PMID- 26827632 TI - Dating the origin and dispersal of Human Papillomavirus type 16 on the basis of ancestral human migrations. AB - A major limitation when reconstructing the origin and evolution of HPV-16 is the lack of reliable substitution rate estimates for the viral genes. On the basis of the hypothesis of human HPV-16 co-divergence, we estimated a mean evolutionary rate of 1.47*10(-7) (95% HPD=0.64-2.47*10(-7)) subs/site/year for the viral LCR region. The results of a Bayesian phylogeographical analysis suggest that the currently circulating HPV-16 most probably originated in Africa about 110 thousand years ago (Kya), before giving rise to four known geographical lineages: the Asian/European lineage, which most probably originated in Asia a mean 38 Kya, and the Asian/American and two African lineages, which probably respectively originated about 33 and 27 Kya. These data closely reflect current hypotheses concerning modern human expansion based on studies of mitochondrial DNA phylogeny. The correlation between ancient human migration and the present HPV phylogeny may be explained by the co-existence of modes of transmission other than sexual transmission. PMID- 26827633 TI - Two novel DNA variants associated with glucose-6-phosphate dehydrogenase deficiency found in Argentine pediatric patients. AB - OBJECTIVE: The enzyme glucose-6-phosphate dehydrogenase (G6PD) catalyses the first step in the pentose phosphate pathway, producing nicotinamide adenine dinucleotide phosphate (NADPH). NADPH plays a crucial role in preventing oxidative damage to proteins and other molecules in cells, mostly red blood cells. G6PD deficiency has an x-linked pattern of inheritance in which hemizygous males are deficient, while females may or may not be deficient depending on the number of affected alleles. We report two novel DNA variants in the G6PD gene detected in two male probands with chronic nonspherocytic hemolytic anemia (CNSHA), who were referred for hematological evaluation. METHOD: Probands and their relatives underwent clinical, biochemical, and molecular assessment. RESULTS: Two novel DNA variants, c.995C>T and c.1226C>A, were found in this study. At the protein level, they produce the substitution of Ser332Phe and Pro409Gln, respectively. These DNA variants were analyzed in the female relatives of probands for genetic counseling. CONCLUSIONS: The novel DNA variants were classified as class I based on the clinical, biochemical, and molecular evaluations performed. PMID- 26827634 TI - Cocaine and crack cocaine abuse by pregnant or lactating mothers and analysis of its biomarkers in meconium and breast milk by LC-MS-A review. AB - Abusive use of drugs is a public health problem worldwide. The use of these substances by pregnant or lactating women can have many serious side effects in newborns. Among the commonest causes of addiction in drug users is cocaine in powdered form, inhaled, intravenously injected or smoked form (crack). Fast screening and a confirmation test using high specificity and sensitivity instruments such as LC-MS or GC/MS, can provide data to qualify and quantify chemical substances present in biological samples such as breast milk or meconium. Cocaine and/or crack can be detected through biomarkers or the unchanged molecule, enabling the form of cocaine use to be distinguished through the analytes. These methods must be carefully developed and validated according to internationally recognized guidelines. Thus, the study of biological matrices in which it can be detected through the development of simple and quick analytical methods can help prevent intoxication and diagnose the symptoms of dependency such as seizures, especially in babies, providing appropriate medical care. PMID- 26827635 TI - The need for inclusion of sex and age of onset variables in genetic association studies of obsessive-compulsive disorder: Overview. AB - Obsessive-compulsive disorder (OCD) is a heterogeneous mental disorder that significantly impairs an individual's functioning. The candidate gene approach has proven to be a useful tool in investigating potential risk genes for OCD, but genetic studies have been largely inconclusive. Etiologically distinct forms of obsessive-compulsive disorder based on sex and age of onset have been identified, yet many genetic studies fail to examine the association by these subtypes. Due to the sexually dimorphic nature of the disorder, positive associations have been found with OCD in males only, suggesting the potential for identifying risk genes that contribute to OCD in women, such as perinatal OCD. This review includes a brief overview of the disorder and its subtypes, with a current update on candidate genes that may contribute to OCD using single nucleotide polymorphisms (SNPs) and genome wide association studies (GWAS). PMID- 26827636 TI - Influence of interactions between genes and childhood trauma on refractoriness in psychiatric disorders. AB - Psychiatric disorders are excellent disease models in which gene-environmental interaction play a significant role in the pathogenesis. Childhood trauma has been known as a significant environmental factor in the progress of, and prognosis for psychiatric illness. Patients with refractory illness usually have more severe symptoms, greater disability, lower quality of life and are at greater risk of suicide than other psychiatric patients. Our literature review uncovered some important clinical factors which modulate response to treatment in psychiatric patients who have experienced childhood trauma. Childhood trauma seems to be a critical determinant of treatment refractoriness in psychotic disorder, bipolar disorder, major depressive disorder, and post-traumatic stress disorder. In patients with psychotic disorders, the relationship between childhood trauma and treatment-refractoriness appears to be mediated by cognitive impairment. In the case of bipolar disorder, the relationship appears to be mediated by greater affective disturbance and earlier onset, while in major depressive disorder the mediating factors are persistent, severe symptoms and frequent recurrence. In suicidal individuals, childhood maltreatment was associated with violent suicidal attempts. In the case of PTSD patients, it appears that childhood trauma makes the brain more vulnerable to subsequent trauma, thus resulting in more severe, refractory symptoms. Given that several studies have suggested that there are distinct subtypes of genetic vulnerability to childhood trauma, it is important to understand how gene-environment interactions influence the course of psychiatric illnesses in order to improve therapeutic strategies. PMID- 26827637 TI - Sulforaphane exerts its anti-inflammatory effect against amyloid-beta peptide via STAT-1 dephosphorylation and activation of Nrf2/HO-1 cascade in human THP-1 macrophages. AB - Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide, accounting for most cases of dementia in elderly individuals, and effective therapies are still lacking. This study was designed to investigate the anti inflammatory properties of sulforaphane against Abeta1-42 monomers in human THP-1 microglia-like cells. The results showed that sulforaphane preferentially inhibited cathepsin B- and caspase-1-dependent NLRP3 inflammasome activation induced by mostly Abeta1-42 monomers, an effect that potently reduced excessive secretion of the proinflammatory cytokine interleukin-1beta (IL-1beta). Subsequent mechanistic studies revealed that sulforaphane mitigated the activation of signal transducer and activator of transcription-1 induced by Abeta1-42 monomers. Sulforaphane also increased nuclear factor erythroid 2 related factor 2 (Nrf2) nuclear translocation, which was followed by upregulation of heme-oxygenase 1 (HO-1). The anti-inflammatory effect of sulforaphane on Abeta1-42-induced IL-1beta production was diminished by small interfering RNA mediated knockdown of Nrf2 or HO-1. Moreover, sulforaphane significantly attenuated the levels of microRNA-146a, which is selectively upregulated in the temporal cortex and hippocampus of AD brains. The aforementioned effects of sulforaphane were replicated by the tyrosine kinase inhibitor, herbimycin A, and Nrf2 activator. These results indicate that signal transducer and activator of transcription-1 dephosphorylation, HO-1 and its upstream effector, Nrf2, play a pivotal role in triggering an anti-inflammatory signaling cascade of sulforaphane that results in decreases of IL-1beta release and microRNA-146a production in Abeta1-42-stimulated human microglia-like cells. These findings suggest that the phytochemical sulforaphane has a potential application in AD therapeutics. PMID- 26827638 TI - Abeta 1-40 enhances the proliferation of human diploid fibroblasts. AB - There is a vast literature on the role of beta amyloid (Abeta) peptides in the pathogenesis of Alzheimer's disease. However, there is a paucity of research on the potential physiological functions of these evolutionarily conserved products of the Abeta precursor protein. Based on previous studies in neuroblastoma cells, we hypothesized that Abeta may contribute to the proliferation of somatic cells. We present evidence supporting this hypothesis for the case of cultured human skin fibroblasts immortalized with the catalytic subunit of human telomerase (hTERT). Optimal concentrations ranged from 100 pM-10 nM, depending on the nature of the assay. PMID- 26827639 TI - Impact of APOE-E4 and family history of dementia on gray matter atrophy in cognitively healthy middle-aged adults. AB - The apolipoprotein E epsilon4 allele (APOE4) and family history of dementia (FH) are well-known risk factors for the development of sporadic Alzheimer's disease. We assessed the effects of these risk factors on gray matter (GM) volume in 295 cognitively healthy middle-aged community-dwelling subjects. Voxel-based morphometry was used to study GM volume differences between high- and low-risk subjects, based on APOE4 carriership (n = 74), first-degree FH (n = 228), or both (n = 62). No significant results were found using a corrected p value. Using a more lenient threshold (p < 0.001 and minimum cluster size of 100 voxels), APOE4 carriers had reduced GM in the striatum compared to noncarriers. Subjects with FH had reduced GM in right precuneus compared to subjects without FH. Maternal and paternal FH provided similar atrophy patterns. APOE4 carriers with FH had GM reductions in bilateral insula compared to subjects with neither APOE4 nor FH. We conclude that a family history of dementia and APOE4 carriership are both associated with regional GM decreases in cognitively healthy middle-aged subjects, with differential effects on brain regions typically affected in Alzheimer's disease. PMID- 26827640 TI - Different patterns of cortical gray matter loss over time in behavioral variant frontotemporal dementia and Alzheimer's disease. AB - We examined patterns of cortical thickness loss and cognitive decline over time in 19 patients with Alzheimer's disease (AD), 10 with behavioral variant frontotemporal dementia (bvFTD), and 34 controls with a mean interval of 2.1 +/- 0.4 years. We measured vertexwise and regional cortical thickness changes of 6 lobar regions of interest between groups with the longitudinal FreeSurfer pipeline. Compared with controls, AD and bvFTD had a steeper rate of cognitive decline and showed faster cortical thinning per year. Decrease of thickness over time was highest in AD and generalized throughout the whole brain, most pronounced posteriorly, whereas bvFTD patients had a more selective loss in frontal cortex and in anterior parts of the temporal lobes. In a direct comparison, AD patients showed faster cortical thinning in the insula, temporal, and parietal regions, whereas bvFTD patients only showed faster cortical thinning in the orbitofrontal gyrus. Decline of cognitive performances was in line with cortical thinning and deteriorated the most in AD patients. PMID- 26827641 TI - Dl-3-n-butylphthalide-induced upregulation of antioxidant defense is involved in the enhancement of cross talk between CREB and Nrf2 in an Alzheimer's disease mouse model. AB - Synapse impairment in the Alzheimer's disease (AD) brain is an early event leading to cognitive dysfunction. Most oxidative stress localizes to the synapse, and synapse loss is the basis of cognitive decline in AD. Dl-3-n-butylphthalide (Dl-NBP), a small molecule compound has been shown to ameliorate oxidative stress. We evaluated the effects of a 5-month oral delivery with Dl-NBP on oxidative stress and cognitive function in APP/PS1 transgenic mice. Dl-NBP treatment reduced oxidative stress in the APP/PS1 mouse brain and alleviated learning and memory deficits. Dl-NBP supplementation meliorated synaptic plasticity, diminished soluble amyloid beta and amyloid beta oligomer in the APP/PS1 mouse brain. Dl-NBP administration caused an increase of cyclic adenosine monophosphate-response element binding protein (CREB)-binding protein (CBP) associated Ser133-phosphorylated CREB (p-CREB) protein. Chromatin immunoprecipitation analysis revealed that Dl-NBP increased the recruitment of CBP to the promoters of best-characterized genes downstream of nuclear factor erythroid 2-related factor 2, nicotinamide adenine dinucleotide phosphate (NADPH) quinone oxidoreductase 1, and gamma-glutamylcysteine synthetase modifier subunit. We demonstrate that the Dl-NBP-triggered upregulation of antioxidant defenses is involved in the enhancement of cross talk between CREB and nuclear factor erythroid 2-related factor 2 via CBP. Our results suggest that Dl-NBP may be a useful agent for the treatment of AD. PMID- 26827642 TI - CSF YKL-40 and pTau181 are related to different cerebral morphometric patterns in early AD. AB - Cerebrospinal fluid (CSF) concentrations of YKL-40 that serve as biomarker of neuroinflammation are known to be altered along the clinico-biological continuum of Alzheimer's disease (AD). The specific structural cerebral correlates of CSF YKL-40 were evaluated across the early stages of AD from normal to preclinical to mild dementia. Nonlinear gray matter (GM) volume associations with CSF YKL-40 levels were assessed in a total of 116 subjects, including normal controls and those with preclinical AD as defined by CSF Abeta < 500 pg/mL, mild cognitive impairment (MCI) due to AD, or mild AD dementia. Age-corrected YKL-40 levels were increased in MCIs versus the rest of groups and showed an inverse u-shaped association with p-tau values. A similar nonlinear relationship was found between GM volume and YKL-40 in inferior and lateral temporal regions spreading to the supramarginal gyrus, insula, inferior frontal cortex, and cerebellum in MCI and AD. These findings for YKL-40 remained unchanged after adjusting for p-tau, which was found to be associated with GM volumes in distinct anatomic areas. CSF YKL 40, a biomarker of glial inflammation, is associated with a cerebral structural signature distinct from that related to p-tau neurodegeneration at the earliest stages of cognitive decline due to AD. PMID- 26827643 TI - Multiplex analyte assays to characterize different dementias: brain inflammatory cytokines in poststroke and other dementias. AB - Both the inflammatory potential and cognitive function decline during aging. The association between the repertoire of inflammatory biomarkers and cognitive decline is unclear. Inflammatory cytokines have been reported to be increased, decreased, or unchanged in the cerebrospinal fluid and sera of subjects with dementia. We assessed 112 postmortem brains from subjects diagnosed with poststroke dementia (PSD), vascular dementia, mixed dementia, and Alzheimer's disease (AD), comparing those to poststroke nondemented (PSND) subjects and age matched controls. We analyzed 5 brain regions including the gray and white matter from the frontal and temporal lobes for a panel of cytokine and/or chemokine analytes using multiplex-array assays. Of the 37 analytes, 14 were under or near the detection limits, 7 were close to the lowest detection level, and 16 cytokines were within the linear range of the assay. We observed widely variable concentrations of C-reactive protein (CRP) and serum amyloid A at the high end (1 150 ng/mg protein), whereas several of the interleukins (IL, interferon-gamma and tumor necrosis factor) at the low end (1-10 pg/mg). There were also regional variations; most notable being high concentrations of some cytokines (e.g., CRP and angiogenesis panel) in the frontal white matter. Overall, we found decreased concentrations of several cytokines, including IL-1 beta (p = 0.000), IL-6 (p = 0.000), IL-7 (p = 0.000), IL-8 (p = 0.000), IL-16 (p = 0.001), interferon inducible protein-10 (0.044), serum amyloid A (p = 0.011), and a trend in IL-1 alpha (p = 0.084) across all dementia groups compared to nondemented controls. IL 6 and IL-8 were significantly lower in dementia subjects than in nondemented subjects in every region. In particular, lower levels of IL-6 and IL-8 were notable in the PSD compared to PSND subjects. Because these 2 stroke groups had comparable degree of vascular pathology, the lower production of IL-6 and IL-8 in PSD reaffirms a possible specific involvement of immunosenescence in dementia pathogenesis. In contrast, CRP was not altered between dementia and nondementia subjects or between PSD and PSND. Our study provides evidence not only for the feasibility of tracking cytokines in postmortem brain tissue but also suggests differentially impaired inflammatory mechanisms underlying dementia including AD. There was a diminished inflammatory response, possibly reflecting immunosenescence and cerebral atrophy, in all dementias. Strategies to enhance anti-inflammatory cytokines and boost the immune system of the brain may be beneficial for preventing cognitive dysfunction, especially after stroke. PMID- 26827644 TI - I forgot when I lost my grip-strong associations between cognition and grip strength in level of performance and change across time in relation to impending death. AB - An association between level of cognitive function and grip strength is well established, whereas evidence for longitudinal associations of change in the 2 functions is still unclear. We examined associations between cognition and grip strength in levels of performance and in longitudinal change in late life in a population-based sample, aged >=80 years at baseline, followed until death. The sample consisted of 449 nondemented individuals drawn from the OCTO-Twin Study. A test battery assessing 6 cognitive domains and grip strength was administered at 5 occasions with measurements intervals of 2 years. We fitted time to death bivariate growth curve models, adjusted for age, education, and sex which resulted in associations between grip strength and cognition in both levels of performance (across all cognitive domains) and rates of change (in 4 of 6 domains). These results show that cognition and grip strength change conjointly in later life and that the association between cognition and grip strength is stronger before death than earlier in life. PMID- 26827645 TI - Age-dependent action of reactive oxygen species on transmitter release in mammalian neuromuscular junctions. AB - Reactive oxygen species (ROS) are implicated in aging, but the neurobiological mechanisms of ROS action are not fully understood. Using electrophysiological techniques and biochemical assays, we studied the age-dependent effect of hydrogen peroxide (H2O2) on acetylcholine release in rat diaphragm neuromuscular junctions. H2O2 significantly inhibited both spontaneous (measured as frequency of miniature end-plate potentials) and evoked (amplitude of end-plate potentials) transmitter release in adult rats. The inhibitory effect of H2O2 was much stronger in old rats, whereas in newborns tested during the first postnatal week, H2O2 did not affect spontaneous release from nerve endings and potentiated end plate potentials. Proteinkinase C activation or intracellular Ca2+ elevation restored redox sensitivity of miniature end-plate potentials in newborns. The resistance of neonates to H2O2 inhibition was associated with higher catalase and glutathione peroxidase activities in skeletal muscle. In contrast, the activities of these enzymes were downregulated in old rats. Our data indicate that the vulnerability of transmitter release to oxidative damage strongly correlates with aging and might be used as an early indicator of senescence. PMID- 26827646 TI - Distinctive pathological mechanisms involved in primary progressive aphasias. AB - Primary progressive aphasia (PPA) comprises a heterogeneous group of neurodegenerative conditions that can be classified in three cliniconeuroanatomic syndromes. Limited information exists, however, about patterns of neuropathologic spreading and microscopic changes underpinning each syndrome. We performed an analysis of a longitudinal in vivo cohort and a postmortem PPA cohort to investigate neurodegeneration over time and to quantify microscopic changes in key language brain areas. The longitudinal analyses demonstrated distinctive patterns of topological extension of brain atrophy. Although semantic variant (sv PPA) showed an eccentric pattern, nonfluent and/or agrammatic (nfv-PPA) and logopenic (lv-PPA) variants showed additional multifocal extension. The quantitative pathology showed that sv-PPA had neuronal loss and thinning in BA 38, whereas nfv-PPA showed thinning in BA 44/45 and evidence of microscopic involvement in BA 40/22. Although lv-PPA showed neuronal loss focused on BA 40/22, imaging results demonstrated widespread left-sided brain atrophy. These analyses provide an account of the pathologic process whereby each variant has stereotypical patterns of brain atrophy extension, which is largely determined by the specific pathologic type. PMID- 26827647 TI - Dopamine modulation of spatial navigation memory in Parkinson's disease. AB - Striatal dopamine depletion is a key pathophysiological feature of Parkinson's disease (PD) causing motor and nonmotor symptoms. Research on nonmotor symptoms has mainly focused on frontostriatal functions. However, dopamine pathways ascending from the ventral tegmental area also innervate hippocampal structures and modulate hippocampal-dependent functions, such as spatial memory. Using a virtual spatial navigation task, we investigated dopaminergic modulation of spatial memory in PD patients in a crossover medication ON/OFF design. We examined medication effects on striatal- and hippocampal-dependent spatial memory by either replacing a location cue in the environment or enlarging its spatial boundary. Key results indicate that in contrast to prior evidence for younger adults, PD patients, like their age-matched controls, rely more on striatal cue based than hippocampal spatial learning. Medication facilitated striatal dependent cue-location learning, whereas medication benefit in hippocampal boundary-related spatial memory depended on prior experience with the task. Medication effects on spatial memory were comparable to and independent of benefits on motor symptoms. These findings shed new light on dopaminergic modulation of hippocampal-striatal functions in PD. PMID- 26827648 TI - Local and distributed PiB accumulation associated with development of preclinical Alzheimer's disease. AB - Amyloid-beta plaques are a hallmark of Alzheimer's disease (AD) that can be assessed by amyloid imaging (e.g., Pittsburgh B compound [PiB]) and summarized as a scalar value. Summary values may have clinical utility but are an average over many regions of interest, potentially obscuring important topography. This study investigates the longitudinal evolution of amyloid topographies in cognitively normal older adults who had normal (N = 131) or abnormal (N = 26) PiB scans at baseline. At 3 years follow-up, 16 participants with a previously normal PiB scan had conversion to PiB scans consistent with preclinical AD. We investigated the multivariate relationship (canonical correlation) between baseline and follow-up PiB topographies. Furthermore, we used penalized regression to investigate the added information derived from PiB topography compared to summary measures. PiB accumulation can be local, that is, a topography predicting the same topography in the future, and/or distributed, that is, one topography predicting another. Both local and distributed PiB accumulation was associated with conversion of PiB status. Additionally, elements of the multivariate topography, and not the commonly used summary scalar, correlated with future PiB changes. Consideration of the entire multivariate PiB topography provides additional information regarding the development of amyloid-beta pathology in very early preclinical AD. PMID- 26827649 TI - The inflammatory markers CRP, IL-6, and IL-10 are associated with cognitive function--data from the Berlin Aging Study II. AB - Inflammation may be an underlying mechanism in cognitive decline. The present study investigated the relationship between cognitive function and the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and IL-10 in a nonclinical sample of elderly adults. Serum levels of CRP, IL-6, and IL-10 were measured in n = 1312 elderly adults (60-85 years, 50.5% females) who underwent comprehensive neuropsychological testing. Multiple linear regression analysis was conducted and adjusted for various demographic and clinical factors. Levels of IL 6, IL-10, and CRP were negatively associated with a composite score of executive function and processing speed, whereas the IL-6 to IL-10 ratio was not predictive for executive function and processing speed. No associations were found between inflammatory markers and verbal episodic memory. These findings suggest a relationship between higher proinflammatory and anti-inflammatory activation of the innate immune system and executive function within the normal range. Further research is needed to examine the relevance of an inflammatory pathway as a potential therapeutic target. PMID- 26827650 TI - Olfactory memory in the old and very old: relations to episodic and semantic memory and APOE genotype. AB - The neuroanatomical organization that underlies olfactory memory is different from that of other memory types. The present work examines olfactory memory in an elderly population-based sample (Swedish National Study on Aging and Care in Kungsholmen) aged 60-100 years (n = 2280). We used structural equation modeling to investigate whether olfactory memory in old age is best conceptualized as a distinct category, differentiated from episodic and semantic memory. Further, potential olfactory dedifferentiation and genetic associations (APOE) to olfactory function in late senescence were investigated. Results are in support of a 3-factor solution where olfactory memory, as indexed by episodic odor recognition and odor identification, is modeled separately from episodic and semantic memory for visual and verbal information. Increasing age was associated with poorer olfactory memory performance, and observed age-related deficits were further exacerbated for carriers of the APOE epsilon4 allele; these effects tended to be larger for olfactory memory compared to episodic and semantic memory pertaining to other sensory systems (vision, auditory). Finally, stronger correlations between olfactory and episodic memory, indicating dedifferentiation, were observed in the older age groups. PMID- 26827651 TI - Twenty-four hours hypothermia has temporary efficacy in reducing brain infarction and inflammation in aged rats. AB - Stroke is a major cause of disability for which no neuroprotective measures are available. Age is the principal nonmodifiable risk factor for this disease. Previously, we reported that exposure to hydrogen sulfide for 48 hours after stroke lowers whole body temperature and confers neuroprotection in aged animals. Because the duration of hypothermia in most clinical trials is between 24 and 48 hours, we questioned whether 24 hours exposure to gaseous hypothermia confers the same neuroprotective efficacy as 48 hours exposure. We found that a shorter exposure to hypothermia transiently reduced both inflammation and infarct size. However, after 1 week, the infarct size became even larger than in controls and after 2 weeks there was no beneficial effect on regenerative processes such as neurogenesis. Behaviorally, hypothermia also had a limited beneficial effect. Finally, after hydrogen sulfide-induced hypothermia, the poststroke aged rats experienced a persistent sleep impairment during their active nocturnal period. Our data suggest that cellular events that are delayed by hypothermia in aged rats may, in the long term, rebound, and diminish the beneficial effects. PMID- 26827653 TI - Alzheimer's disease-like pathology has transient effects on the brain and blood metabolome. AB - The pathogenesis of Alzheimer's disease (AD) is complex involving multiple contributing factors. The extent to which AD pathology affects the metabolome is still not understood nor is it known how disturbances change as the disease progresses. For the first time, we have profiled longitudinally (6, 8, 10, 12, and 18 months) both the brain and plasma metabolome of APPswe/PS1deltaE9 double transgenic and wild-type mice. A total of 187 metabolites were quantified using a targeted metabolomic methodology. Multivariate statistical analysis produced models that distinguished APPswe/PS1deltaE9 from wild-type mice at 8, 10, and 12 months. Metabolic pathway analysis found perturbed polyamine metabolism in both brain and blood plasma. There were other disturbances in essential amino acids, branched-chain amino acids, and also in the neurotransmitter serotonin. Pronounced imbalances in phospholipid and acylcarnitine homeostasis were evident in 2 age groups. AD-like pathology, therefore, affects greatly on both the brain and blood metabolomes, although there appears to be a clear temporal sequence whereby changes to brain metabolites precede those in blood. PMID- 26827654 TI - Increased bone morphogenetic protein signaling contributes to age-related declines in neurogenesis and cognition. AB - Aging is associated with decreased neurogenesis in the hippocampus and diminished hippocampus-dependent cognitive functions. Expression of bone morphogenetic protein 4 (BMP4) increases with age by more than 10-fold in the mouse dentate gyrus while levels of the BMP inhibitor, noggin, decrease. This results in a profound 30-fold increase in phosphorylated-SMAD1/5/8, the effector of canonical BMP signaling. Just as observed in mice, a profound increase in expression of BMP4 is observed in the dentate gyrus of humans with no known cognitive abnormalities. Inhibition of BMP signaling either by overexpression of noggin or transgenic manipulation not only increases neurogenesis in aging mice, but remarkably, is associated with a rescue of cognitive deficits to levels comparable to young mice. Additive benefits are observed when combining inhibition of BMP signaling and environmental enrichment. These findings indicate that increased BMP signaling contributes significantly to impairments in neurogenesis and to cognitive decline associated with aging, and identify this pathway as a potential druggable target for reversing age-related changes in cognition. PMID- 26827655 TI - White matter hyperintensities characterize monogenic frontotemporal dementia with granulin mutations. AB - No study but one has suggested the presence of white matter hyperintensities (WMHs) in frontotemporal dementia (FTD), limited to 4 cases carrying pathogenic Granulin (GRN) gene mutations. We investigated the presence of WMHs in a cohort of 14 FTD patients with pathogenic GRN mutations (GRN+), 28 patients without GRN mutations (GRN-) and 18 healthy controls (HC). We further considered 11 asymptomatic GRN+ subjects and 11 young age-matched healthy controls (yHC). The WMH burden was automatically computed and a voxelwise-based analysis was carried out to explore the differences in WMH brain spatial distribution. FTD-GRN+ patients had increased total WMH burden than both HC (p < 0.001) and FTD-GRN-(p = 0.01) groups. WMHs were mainly localized in the right middle frontal and superior temporal gyri, in the left superior frontal in the left parietal gyri. No significant differences of WMH burden between asymptomatic GRN+ and yHC were observed. The presence of WMHs in cases of FTD may suggest a novel mechanism of GRN disease-related neurodegeneration, may be of help in the differential diagnosis, and in guiding genetic screening. PMID- 26827656 TI - Serum BDNF correlates with connectivity in the (pre)motor hub in the aging human brain--a resting-state fMRI pilot study. AB - Brain-derived neurotrophic factor (BDNF) has been discussed to be involved in plasticity processes in the human brain, in particular during aging. Recently, aging and its (neurodegenerative) diseases have increasingly been conceptualized as disconnection syndromes. Here, connectivity changes in neural networks (the connectome) are suggested to be the most relevant and characteristic features for such processes or diseases. To further elucidate the impact of aging on neural networks, we investigated the interaction between plasticity processes, brain connectivity, and healthy aging by measuring levels of serum BDNF and resting state fMRI data in 25 young (mean age 24.8 +/- 2.7 (SD) years) and 23 old healthy participants (mean age, 68.6 +/- 4.1 years). To identify neural hubs most essentially related to serum BDNF, we applied graph theory approaches, namely the new data-driven and parameter-free approach eigenvector centrality (EC) mapping. The analysis revealed a positive correlation between serum BDNF and EC in the premotor and motor cortex in older participants in contrast to young volunteers, where we did not detect any association. This positive relationship between serum BDNF and EC appears to be specific for older adults. Our results might indicate that the amount of physical activity and learning capacities, leading to higher BDNF levels, increases brain connectivity in (pre)motor areas in healthy aging in agreement with rodent animal studies. Pilot results have to be replicated in a larger sample including behavioral data to disentangle the cause for the relationship between BDNF levels and connectivity. PMID- 26827652 TI - Discovery of gene-gene interactions across multiple independent data sets of late onset Alzheimer disease from the Alzheimer Disease Genetics Consortium. AB - Late-onset Alzheimer disease (AD) has a complex genetic etiology, involving locus heterogeneity, polygenic inheritance, and gene-gene interactions; however, the investigation of interactions in recent genome-wide association studies has been limited. We used a biological knowledge-driven approach to evaluate gene-gene interactions for consistency across 13 data sets from the Alzheimer Disease Genetics Consortium. Fifteen single nucleotide polymorphism (SNP)-SNP pairs within 3 gene-gene combinations were identified: SIRT1 * ABCB1, PSAP * PEBP4, and GRIN2B * ADRA1A. In addition, we extend a previously identified interaction from an endophenotype analysis between RYR3 * CACNA1C. Finally, post hoc gene expression analyses of the implicated SNPs further implicate SIRT1 and ABCB1, and implicate CDH23 which was most recently identified as an AD risk locus in an epigenetic analysis of AD. The observed interactions in this article highlight ways in which genotypic variation related to disease may depend on the genetic context in which it occurs. Further, our results highlight the utility of evaluating genetic interactions to explain additional variance in AD risk and identify novel molecular mechanisms of AD pathogenesis. PMID- 26827658 TI - Association of body mass index and the depletion of nigrostriatal dopamine in Parkinson's disease. AB - Several antecedent studies had reported close relationship between low body weight and Parkinson's disease (PD). However, there have been few investigations about the role of body weight to nigrostriatal dopaminergic neurodegeneration. This study enrolled 398 de novo patients with PD whom underwent [18F] N-(3 Fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane positron emission tomography scan and body mass index (BMI) measurement. The relationships between BMI and dopamine transporter (DAT) activity were analyzed using linear regression analysis. A multivariate analysis adjusted for age, gender, disease duration, smoking status, coffee and tea consumption, and residence area revealed that BMI remained independently and significantly associated with DAT activity in all striatal subregions. Moreover, multiple logistic regression analyses showed that BMI was a significant predictor for the lowest quartile of DAT activity in the anterior putamen, ventral striatum, caudate nucleus, and total striatum. The present findings suggest that a low BMI might be closely associated with low density of nigrostriatal dopaminergic neurons in PD, which could support the evidence for the role of low body weight to PD-related pathologies. PMID- 26827657 TI - Cortical thinning of parahippocampal subregions in very early Alzheimer's disease. AB - The stereotypical pattern of neurofibrillary tangle spreading in the earliest stages of typical Alzheimer's dementia (AD) predicts that medial perirhinal cortex (mPRC) atrophy precedes entorhinal cortex (ERC) atrophy, whereas the status of the parahippocampal cortex (PHC) remains unclear. Atrophy studies have focused on more advanced rather than early AD patients, and usually segment the entire PRC as opposed to the mPRC versus lateral PRC (lPRC). The present study therefore determined the extent of ERC, mPRC, lPRC, and PHC atrophy in very early AD (mean Mini-Mental State Examination score = 26) patients and its presumed prodrome amnestic mild cognitive impairment (mean Mini-Mental State Examination score = 28) compared to demographically matched controls. PHG structures were manually segmented (blinded rater) and cortical thicknesses extracted. ERC and mPRC were similarly atrophied in both patient groups. The lPRC was atrophied in the AD group only. Thus, atrophic changes in very early AD broadly map onto the pattern of neurofibrillary tangle spreading and suggest that mPRC, ERC, and lPRC, but not PHC-associated functional impairments, characterize very early-stage AD. PMID- 26827659 TI - Stem Cell Harvesting after Bortezomib-Based Reinduction for Myeloma Relapsing after Autologous Transplantation: Results from the British Society of Blood and Marrow Transplantation/United Kingdom Myeloma Forum Myeloma X (Intensive) Trial. AB - The phase III British Society of Blood and Marrow Transplantation/United Kingdom Myeloma Forum Myeloma X trial (MMX) demonstrated prospectively, for the first time, superiority of salvage autologous stem cell transplantation over chemotherapy maintenance for multiple myeloma (MM) in first relapse after previous ASCT. However, many patients have stored insufficient stem cells (PBSC) for second ASCT and robust evidence for remobilization after first ASCT is lacking. We report the feasibility, safety, and efficacy of remobilization after bortezomib-doxorubicin-dexamethasone reinduction in MMX and outcomes of second ASCT with these cells. One hundred ten patients underwent >=1 remobilization with 32 and 4, undergoing second and third attempts, respectively. Toxicities of remobilization were similar to those seen in first-line mobilization. After all attempts, 52% of those with insufficient previously stored PBSC had harvested a sufficient quantity to proceed to second ASCT. Median PBSC doses infused, neutrophil engraftment, and time to discharge after second ASCT were similar regardless of stem cell source, as were the toxicities of second ASCT. No significant differences between PBSC sources were noted in depth of response to ASCT or time to progression. Harvesting after bortezomib-doxorubicin dexamethasone reinduction for MM at first relapse is safe and feasible and yields a reliable cell product for second ASCT. The study is registered with ClinicalTrials.gov (NCT00747877) and EudraCT (2006-005890-24). PMID- 26827660 TI - Targeting CD138-/CD20+ Clonogenic Myeloma Precursor Cells Decreases These Cells and Induces Transferable Antimyeloma Immunity. AB - This phase Ib clinical trial evaluated whether pretargeting of CD20(+) clonogenic myeloma precursor cells (CMPCs) with anti-CD3 * anti-CD20 bispecific antibody armed T cells (BATs) before autologous stem cell transplantation (SCT) in patients with standard-risk and high-risk multiple myeloma would induce antimyeloma immunity that could be detected and boosted after SCT. All 12 patients enrolled in this study received 2 BATs infusions before SCT, and 4 patients received a booster infusion of BATs after SCT. Pretargeting CD138( )/CD20(+) CMPCs with BATs before SCT was safe and reduced levels of CMPCs by up to 58% in the postinfusion bone marrow in patients who remained in remission. Four of 5 patients who remained in remission had a >5-fold increase in IFN-gamma enzyme-linked immunospot responses. SOX2 antibody increased after BATs infusions and persisted after SCT. The median anti-SOX2 level at 3 months after SCT was 28.1 ng/mL (range, 4.6 to 256 ng/mL) in patients who relapsed and 46 ng/mL (range, 28.3 to 73.3 ng/mL) in patients who remained in remission. The immune correlates suggest that infusions of targeted T cells given before SCT were able to reduce CMPC levels and induced cellular and humoral antimyeloma immunity that could be transferred and boosted after SCT. PMID- 26827661 TI - Overexpression of hypoxia-inducible factor-1 alpha improves vasculogenesis related functions of endothelial progenitor cells. AB - Postnatal vasculogenesis is mediated by mobilization of endothelial progenitor cells (EPCs) from bone marrow and homing to ischemic tissues. This feature emphasizes this cell type for cell-based therapies aiming at the improvement of neovascularization in tissue engineering applications and regenerative medicine. In animal models, it was demonstrated that implantation of EPCs from cord blood (cbEPCs) led to the formation of a complex functional neovasculature, whereas EPCs isolated from adult peripheral blood (pbEPCs) showed a limited vasculogenic potential, which may be attributed to age-related dysfunction. Recently, it was demonstrated that activation of hypoxia-inducible factor-1alpha (Hif-1alpha) improves cell functions of progenitor cells of mesenchymal and endothelial origin. Thus, we hypothesized that overexpression of Hif-1alpha may improve the vasculogenesis-related phenotype of pbEPCs. In the present study, we overexpressed Hif-1alpha in pbEPCs and cbEPCs by using recombinant adenoviruses and investigated effects on stem cell- and vasculogenesis-related cell parameters. Overexpression of Hif-1alpha enhanced proliferation, invasion, cell survival and in vitro capillary sprout formation of both EPC populations. Migration was increased in cbEPCs upon Hif-1alpha overexpression, but not in pbEPCs. Cellular senescence was decreased in pbEPCs, while remained in cbEPCs, which showed, as expected, intrinsically a dramatically lower senescent phenotype in relation to pbEPCs. Similarly, the colony-formation capacity was much higher in cbEPCs in comparison to pbEPCs and was further increased by Hif-1alpha overexpression, whereas Hif-1alpha transduction exerted no significant influence on colony formation of pbEPCs. In summary, our experiments illustrated multifarious effects of Hif-1alpha overexpression on stem cell and vasculogenic parameters. Therefore, Hif-1alpha overexpression may represent a therapeutic option to improve cellular functions of adult as well as postnatal EPCs. PMID- 26827662 TI - Combination of drug-conjugated SWCNT nanocarriers for efficient therapy of cancer stem cells in a breast cancer animal model. AB - Targeting breast cancer and more specifically cancer stem cell (CSC) subpopulation, responsible for tumor growth, resistance and self-renewal, using combination of therapeutic drugs selectively delivered via biocompatible nanocarriers, provides a novel approach for effective therapy. Here, we propose to evaluate the potential therapeutic efficacy of combining Paclitaxel and Salinomycin drugs actively targeted to both breast cancer and CSCs in xenograft murine model after conjugation with biocompatible CD44 antibody conjugated SWCNTs via hydrazone linker allowing pH-responsive release mechanism near the acidic tumor microenvironment. Both in vitro investigations on MDA-MB-231, sorted CSC negative or CSC positive fractions and in vivo evaluations on tumor-bearing mice using noninvasive bioluminescence and magnetic resonance imaging confirmed the enhanced therapeutic effect of the combined therapy compared to treatment with individual drug-conjugated nanocarriers or free drug suspensions. Thus, confirmed the great promise of the developed SWCNTs drug delivery system for effective breast cancer treatment by targeting and eradicating both whole tumor cells and CSCs populations. PMID- 26827663 TI - Recombinant M2e outer membrane vesicle vaccines protect against lethal influenza A challenge in BALB/c mice. AB - Currently approved influenza vaccines predominantly protect through antibodies directed against the highly variable glycoprotein hemagglutinin (HA), necessitating annual redesign and formulation based on epidemiological prediction of predominant circulating strains. More conserved influenza protein sequences, such as the ectodomain of the influenza M2 protein, or M2e, show promise as a component of a universal influenza A vaccine, but require a Th1-biased immune response for activity. Recently, recombinant, bacterially derived outer membrane vesicles (OMVs) demonstrated potential as a platform to promote a Th1-biased immune response to subunit antigens. Here, we engineer three M2e-OMV vaccines and show that all elicit strong IgG titers, with high IgG2a:IgG1 ratios, in BALB/c mice. Additionally, the administration of one M2e-OMV construct containing tandem heterologous M2e peptides (M2e4xHet-OMV) resulted in 100% survival against lethal doses of the mouse-adapted H1N1 influenza strain PR8. Passive transfer of antibodies from M2e4xHet-OMV vaccinated mice to unvaccinated mice also resulted in 100% survival to challenge, indicating that protection is driven largely via antibody-mediated immunity. The potential mechanism through which M2e-OMVs initiated the immune response was explored and it was found that the constructs triggered TLR1/2, TLR4, and TLR5. Our data indicate that OMVs have potential as a platform for influenza A vaccine development due to their unique adjuvant profile and intrinsic pathogen-mimetic nature. PMID- 26827664 TI - Diverse effects on vaccine-specific serum IgG titres and memory B cells upon methotrexate and anti-TNF-alpha therapy in children with rheumatic diseases: A cross-sectional study. AB - OBJECTIVES: We aimed at a comprehensive evaluation of how anti-TNF-alpha therapy and methotrexate treatment interferes with B cell memory in children with Paediatric Rheumatic Disease (PRD), by evaluating existing B cell phenotypes, and preserved vaccine-specific memory B cells and IgG titres generated prior to disease and treatment. METHODS: In a cross-sectional study on children with PRD on various treatments, we measured titre levels and avidity strength of serum IgG specific against measles, rubella and tetanus. We also quantified transitional B cells and resting, atypical, and activated memory B cells with flow cytometry, and enumerated antigen-specific memory B cells with ELISpot. RESULTS: For children who had received a tetanus booster, patients treated with any disease modifying anti-rheumatic drug (DMARD) had lower tetanus serum IgG compared to healthy controls and NSAID-treated patients. Patients without a measles booster had lower levels of measles-specific memory B cells, but all vaccine-specific memory B cells were preserved in patients with booster. We furthermore found that the mature B cell compartment was phenotypically similar between patients and healthy controls. CONCLUSIONS: We concluded that the general and vaccine-specific memory B cell compartment is well preserved in children with PRD and DMARD treatment, but that they might have lower serum tetanus IgG. We emphasize the importance for these children to follow the full vaccination schedule, and suggest to re-measure tetanus titres as they reach adulthood. PMID- 26827665 TI - Treatment of cesarean scar pregnancy: another chapter in the fertility preservation saga. PMID- 26827668 TI - Improving reporting of research reports. PMID- 26827666 TI - Estrogen receptor beta regulates endometriotic cell survival through serum and glucocorticoid-regulated kinase activation. AB - OBJECTIVE: To determine the expression and biological roles of serum and glucocorticoid-regulated kinase (SGK1) in tissues and cells from patients with endometriosis and from healthy control subjects. DESIGN: Case-control. SETTING: University research setting. PATIENT(S): Premenopausal women. INTERVENTION(S): Endometriotic tissues were obtained from women with ovarian endometriosis, and normal endometrial tissues were obtained from women undergoing hysterectomy for benign conditions. MAIN OUTCOME MEASURE(S): Expression levels of SGK1, the role of SGK1 in endometriosis pathology, and regulation of SGK1 by estrogen receptor (ER) beta. RESULT(S): Transcript and protein levels of SGK1 were significantly higher in endometriotic tissues and cells compared with normal endometrium. SGK1 mRNA and protein levels were stimulated by E2, by the ERbeta-selective agonist diarylpropionitrile, and by prostaglandin E2. SGK1 was transcriptionally regulated by ERbeta based on small interfering RNA knockdown and chromatin immunoprecipitation of ERbeta followed by quantitative polymerase chain reaction. SGK1 knockdown led to increased cleavage of poly(ADP-ribose) polymerase, and SGK1 activation was correlated with the phosphorylation of FOXO3a, a proapoptotic factor. CONCLUSION(S): ERbeta leads to SGK1 overexpression in endometriosis, which contributes to the survival of endometriotic lesions through inhibition of apoptosis. PMID- 26827667 TI - Searching for a common mechanism for placenta-mediated pregnancy complications and cardiovascular disease: role of lipoprotein(a). AB - OBJECTIVE: To investigate lipoprotein(a) [Lp(a)], a well known cardiovascular risk factor, in women with history of placenta-mediated pregnancy complications (PMPC) compared with healthy uneventful-pregnancy women (HW), and the role of LPA gene functional polymorphisms in modulating both Lp(a) levels and PMPC risk. DESIGN: Retrospective observational study. SETTING: University hospital. PATIENT(S): A total of 360 women with history of PMPC (154 preeclampsia [PE], 121 stillbirth [SB], and 85 small for gestational age [SGA]) and 270 HW. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Lp(a) levels measurement and LPA +93C >T and +121G>A polymorphisms genotyping. RESULT(S): In PMPCs we observed higher Lp(a) levels than those found in HW and an association with PMPC risk, also after adjustment for age, familial history of cardiovascular disease, and traditional risk factors. By analyzing Lp(a) concentrations according to each pregnancy complication, we observed significantly higher Lp(a) levels in women with history of SB and PE, conferring 2.5-fold and 2-fold increased risks, respectively; no association with SGA was observed. Lp(a) concentrations progressively and significantly increased as LPA unfavorable allelic burden increased; unfavorable allelic burden influenced SB and PE risk. CONCLUSION(S): We evidenced, for the first time, an association between high Lp(a) concentrations and history of SB, and we confirmed the role of Lp(a) in PE risk; this well known atherothrombotic marker might represent one of the possible mechanisms shared by PMPC and cardiovascular disease. PMID- 26827669 TI - Mosaicism: "survival of the fittest" versus "no embryo left behind". PMID- 26827670 TI - Carotid Endarterectomy: How Surgeons, Neurologists, and Internists Can Be Greater Than the Sum of Their Parts. PMID- 26827671 TI - Amplification and pyrosequencing of near-full-length hepatitis C virus for typing and monitoring antiviral resistant strains. AB - Directly acting antiviral drugs have contributed considerable progress to hepatitis C virus (HCV) treatment, but they show variable activity depending on virus genotypes and subtypes. Therefore, accurate genotyping including recombinant form detection is still of major importance, as is the detection of resistance-associated mutations in case of therapeutic failure. To meet these goals, an approach to amplify the HCV near-complete genome with a single long range PCR and sequence it with Roche GS Junior was developed. After optimization, the overall amplification success rate was 73% for usual genotypes (i.e. HCV 1a, 1b, 3a and 4a, 16/22) and 45% for recombinant forms RF_2k/1b (5/11). After pyrosequencing and subsequent de novo assembly, a near-full-length genomic consensus sequence was obtained for 19 of 21 samples. The genotype and subtype were confirmed by phylogenetic analysis for every sample, including the suspected recombinant forms. Resistance-associated mutations were detected in seven of 13 samples at baseline, in the NS3 (n = 3) or NS5A (n = 4) region. Of these samples, the treatment of one patient included daclatasvir, and that patient experienced a relapse. Virus sequences from pre- and posttreatment samples of four patients who experienced relapse after sofosbuvir-based therapy were compared: the selected variants seem too far from the NS5B catalytic site to be held responsible. Although tested on a limited set of samples and with technical improvements still necessary, this assay has proven to be successful for both genotyping and resistance-associated variant detection on several HCV types. PMID- 26827672 TI - Prevalence and molecular characteristics of urinary and intestinal microsporidia infections in renal transplant recipients. AB - Transplant recipients have been identified as a new risk group for microsporidia infection. We characterize for the first time the prevalence of microsporidia in intestinal and urinary tracts of renal transplant recipients. Molecular examination of 86 patients showed that 25.5% of them were infected; 86% were confirmed to have pathogens in their urine and 45.5% in stool. Among positive patients, 32% had microsporidia confirmed in both urine and stool. Genotyping revealed Encephalitozoon cuniculi (59%) and Enterocytozoon bieneusi (23%) monoinfections as well as coinfections with both species (18%). Moreover, we found diarrhoea and fever as symptoms significantly associated with microsporidia presence. Our results indicate that microsporidial infection should be considered in the assessment of renal transplant recipients, especially in the urinary tract, even if asymptomatic. Molecular identification of microsporidia species is relevant because of their different susceptibility for treatment. PMID- 26827674 TI - Mucilaginibacter yixingensis sp. nov., isolated from vegetable soil. AB - A Gram-reaction-negative, aerobic, non-motile, non-spore-forming, rod-shaped bacterium, designated YX-36T, was isolated from a vegetable plot in Yixing, Jiangsu province, China. The strain grew at 15-37 degrees C (optimally at 37 degrees C), at pH 6.0-9.5 (optimally at pH 6.5) and in the presence of 0-1% (w/v) NaCl (optimally without NaCl). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YX-36T was related most closely to Mucilaginibacter herbaticus DR-9T (96.88% similarity), followed by Mucilaginibacter sabulilitoris SMS-12T (95.78%), Mucilaginibacter polysacchareus DR-f3T (95.77%) and Mucilaginibacter polysacchareus DRP28T (95.77%). The DNA G+C content of strain YX 36T was 47.2 mol%. The only isoprenoid quinone was menaquinone 7 (MK-7). The major polar lipids were phosphatidylethanolamine and aminophospholipid. The major fatty acids were iso-C15:0, summed feature 3 (iso-C15:0 2-OH/C16:1omega7c) and iso-C17:0 3-OH. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain YX-36T represents a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacter yixingensis sp. nov. is proposed. The type strain is YX 36T (=DSM 26809T=CCTCC AB 2012880T). PMID- 26827673 TI - Tert-butylhydroquinone compromises survival in murine experimental stroke. AB - Tert-butylhydroquinone (tBHQ), an Nrf2 signaling pathway inducer that is widely used as a food additive in the U.S., prevents oxidative stress-induced cytotoxicity in neurons. This study assesses the effects of tBHQ on ischemic stroke outcomes in mice. We measured infarct size, neurological deficits, and brain volume after tBHQ treatments in murine permanent middle cerebral artery occlusion (pMCAO) model in vivo. Further, we evaluated the regulation of tBHQ on mitochondrial function in cerebrovascular endothelial cells in vitro, which is critical to the blood-brain barrier (BBB) permeability. Our results demonstrated that tBHQ increased post-stroke mortality and worsened stroke outcomes. Mitochondrial function was suppressed by tBHQ treatment of cerebrovascular endothelial cells, and this suppression was potentiated by co-treatment with lipopolysaccharide (LPS), the bacterial mimic. These data indicate that tBHQ exacerbated stroke damage might due to the compromised BBB permeability in permanent stroke. PMID- 26827675 TI - A transcriptional target of androgen receptor, miR-421 regulates proliferation and metabolism of prostate cancer cells. AB - Prostate cancer is one of the most common malignancies, and microRNAs have been recognized to be involved in tumorigenesis of various kinds of cancer including prostate cancer (PCa). Androgen receptor (AR) plays a core role in prostate cancer progression and is responsible for regulation of numerous downstream targets including microRNAs. This study identified an AR-repressed microRNA, miR 421, in prostate cancer. Expression of miR-421 was significantly suppressed by androgen treatment, and correlated to AR expression in different prostate cancer cell lines. Furthermore, androgen-activated AR could directly bind to androgen responsive element (ARE) of miR-421, as predicted by bioinformatics resources and demonstrated by ChIP and luciferase reporter assays. In addition, over-expression of miR-421 markedly supressed cell viability, delayed cell cycle, reduced glycolysis and inhibited migration in prostate cancer cells. According to the result of miR-421 target genes searching, we focused on 4 genes NRAS, PRAME, CUL4B and PFKFB2 based on their involvement in cell proliferation, cell cycle progression and metabolism. The expression of these 4 downstream targets were significantly repressed by miR-421, and the binding sites were verified by luciferase assay. Additionally, we explored the expression of miR-421 and its target genes in human prostate cancer tissues, both in shared microarray data and in our own cohort. Significant differential expression and inverse correlation were found in PCa patients. PMID- 26827679 TI - Impact of a candidaemia care bundle on patient care at a large teaching hospital in England. PMID- 26827681 TI - Diabetes in Older Adults: Starting a National Dialogue. PMID- 26827680 TI - A new structural model of Alzheimer's Abeta42 fibrils based on electron paramagnetic resonance data and Rosetta modeling. AB - Brain deposition of Abeta in the form of amyloid plaques is a pathological hallmark of Alzheimer's disease. There are two major species of Abeta in the brain: Abeta42 and Abeta40. Although Abeta40 is several-fold more abundant than Abeta42 in soluble form, Abeta42 is the major component of amyloid plaques. Structural knowledge of Abeta42 fibrils is important both for understanding the process of Abeta aggregation and for designing fibril-targeting drugs. Here we report site-specific structural information of Abeta42 fibrils at 22 residue positions based on electron paramagnetic resonance data. In combination with structure prediction program Rosetta, we modeled Abeta42 fibril structure at atomic resolution. Our Abeta42 fibril model consists of four parallel in-register beta-sheets: betaN (residues ~7-13), beta1 (residues ~17-20), beta2 (residues ~32 36), and betaC (residues 39-41). The region of beta1-loop-beta2 in Abeta42 fibrils adopts similar structure as that in Abeta40 fibrils. This is consistent with our cross seeding data that Abeta42 fibril seeds shortened the lag phase of Abeta40 fibrillization. On the other hand, Abeta42 fibrils contain a C-terminal beta-arc-beta motif with a special turn, termed "arc", at residues 37-38, which is absent in Abeta40 fibrils. Our results can explain both the higher aggregation propensity of Abeta42 and the importance of Abeta42 to Abeta40 ratio in the pathogenesis of Alzheimer's disease. PMID- 26827682 TI - Influence of Blood Pressure and Other Clinical Variables on Long-Term Mortality in a Cohort of Elderly Subjects with Type 2 Diabetes. AB - BACKGROUND: Diabetes mellitus and high blood pressure (HBP) are commonly associated conditions in the elderly population. An effect of treatments, biologic and anthropometric variables on long-term mortality is unknown in this population. OBJECTIVES: To determine the prevalence of HBP control in a sample of elderly patients with type 2 diabetes with office blood pressure (BP) readings and ambulatory blood pressure monitoring (ABPM) and evaluate the influence of BP, anthropometric and laboratory variables on long term mortality. METHODS: Cohort study in patients living at home in the area of Sherbrooke, >=65 years old, receiving reimbursement for antidiabetic medication. The study included medical history, 2 sets of BP measurements, 2 24-hour urinary collections for microalbuminuria, 1 24-hour ABPM, blood level of creatinine and glycosylated hemoglobin. Charts were reanalyzed 8 years later for analysis of cardiovascular and total mortality cases. RESULTS: 198 patients were initially recruited. By history, 83% of the subjects had diagnoses and treatments for high blood pressure. In multivariate analysis, factors associated with an 8-year increased risk for cardiovascular mortality were creatinine >=84 umol/L, office seated systolic blood pressure <=130 and diastolic BP <=67.6 over 24 hours. Factors associated with total mortality were lower waist circumference, serum creatinine >=84 and diastolic BP <=67.6 over 24 hours. CONCLUSIONS: Lower systolic and diastolic BP (office and ABPM), lower waist circumference and higher creatinine values are associated with an increased mortality risk. This suggests that a lower BP, declining kidney function and frailty are factors associated with this observation. PMID- 26827683 TI - Diabetes Management in Long-Term Care: An Exploratory Study of the Current Practices and Processes to Managing Frail Elderly Persons with Type 2 Diabetes. AB - OBJECTIVES: There is limited evidence for the management of diabetes in frail elderly residents living in long-term care (LTC) settings. The purpose of this study was to explore the current practices of glycemic management in frail elderly persons with diabetes living in LTC settings. METHODS: Using a mixed methods convergent parallel design, this study surveyed medical directors and attending physicians of long-term care centres through an online questionnaire and one-on-one semistructured interviews. RESULTS: A total of 39 questionnaires were completed, representing a variety of LTC settings, including private and public settings. Diabetes management practices varied across the participating settings with respect to glucose targets, with 69% of respondents selecting glycated hemoglobin levels of 8% or greater as being appropriate for LTC residents. Blood glucose monitoring, pharmacotherapy, presence of comorbidities, frailty and life expectancy were highlighted as variables for consideration in diabetes management in LTC. Interviews with attending physicians further illustrated the variability of opinions related to the use of clinical practice guidelines, glucose target levels and intensity of management (i.e. blood glucose monitoring and pharmacotherapy). CONCLUSIONS: The findings of this study were triangulated with both the quantitative survey and the qualitative interviews. The implications of these findings suggest a disparity between what physicians feel should be achieved for diabetes management and what is actually done for frail elderly adults in LTC settings. Further research needs to be completed to assess the distinct needs and considerations of this unique population and healthcare setting. PMID- 26827684 TI - Evaluating the Effect of a Diabetes Health Coach in Individuals with Type 2 Diabetes. AB - OBJECTIVES: Diabetes health coaching has not been adequately assessed in individuals with type 2 diabetes. The objective of this review was to synthesize the evidence of health coaching for individuals with diabetes to determine the effects of coaching on diabetes control, specifically on glycated hemoglobin (A1C) levels. METHODS: The EMBASE, MEDLINE, CINAHL, PsychINFO and Cochrane Central Register of Controlled Trials databases were searched from inception to January 2015. Reference lists from important publications were also reviewed. At least 2 evaluators independently screened and extracted data from eligible studies. RESULTS: A total of 8 trials met the selection criteria, which included 724 adult participants; 353 participants were randomized to a diabetes health coaching intervention, and 371 were randomized to usual care. The pooled effect of diabetes health coaching overall was a statistically significant reduction of A1C levels by 0.32 (95% CI, -0.50 to -0.15). Longer diabetes health coaching exposure (>6 months) resulted in a 0.57% reduction in A1C levels (95% CI, -0.76 to -0.38), compared to shorter diabetes health coaching exposure (<=6 months) ( 0.23%; 95% CI, -0.37 to -0.09). Across all studies, diabetes health coaching consisted of goal setting, knowledge acquisition, individualized care and frequent follow up. CONCLUSIONS: Diabetes health coaching has an emerging role in healthcare that facilitates self-care, behaviour change and offers frequent follow up and support. This review finds that health coaching for those with diabetes is an effective intervention for improving glycemic control, which may be of greater benefit when offered in addition to existing diabetes care. PMID- 26827685 TI - Management and Prevention of Percutaneous Iliac Stent Infection: A Case Report. AB - A 52-year-old man was admitted in the emergency department for deteriorating mental status and suspicion of discitis. Computed tomography and positron emission tomography scan showed evidence of localized infection of the aortic bifurcation and blood cultures were positive for Staphylococcus aureus. Ten years ago, the patient underwent placement of covered metal stents on each common iliac artery due to arteritic stenosis. The infected material was removed and aortic bifurcation repaired using an autologous femoral vein graft. This case report describes the surgical procedure, patient outcome, and review on prevention of such complications. PMID- 26827686 TI - Deep Vein Thrombosis and True Crural Aneurysm: Misdiagnosis or Causal Relation? AB - True crural artery aneurysm is a rare clinical entity. Crural artery aneurysms are most frequently seen in men in their sixth decade without major cardiopulmonary diseases and are often associated with injury, superinfection, or vasculitis. We report the case of a 44-year-old man with a history of idiopathic deep vein thrombosis (DVT) as the first manifestation of a true crural artery aneurysm. To our knowledge, DVT is very rarely related with true crural artery aneurysms, with only 3 cases reported in the current literature. Open surgical repair is the most common management, with ligation as a second option in emergencies such as rupture. The related literature is discussed. We conclude that crural aneurysms should be considered in differential diagnosis of popliteal DVT in adults. True crural aneurysms need vigilance and a more systematical approach to provide physicians the means to the best medical care. PMID- 26827687 TI - Prognostic risk factors for treatment decision in pT1a,b N0M0 HER2-positive breast cancers. AB - Although outcomes for women with breast cancers may vary by biologic subtype, patients with T1a,b N0M0 tumors have an excellent prognosis across all subgroups. HER2 overexpression occurs in 15-20% of primary breast tumors, and is associated with diminished disease-free and overall survival. The anti-HER2 monoclonal antibody trastuzumab in combination with chemotherapy is an effective treatment for all stages of HER2 positive breast cancer (bc). However, the absolute benefit decreases as the risk of recurrence lessens and no available randomized adjuvant trial has evaluated the role of trastuzumab in women with pT1a,b N0M0, HER2 positive breast tumors. These findings may explain the debate about the appropriate indication for adjuvant chemotherapy plus trastuzumab in this setting of patients. The aim of this review was to describe known and novel prognostic risk factors to be used for tailored treatment decision in pT1a,b N0M0 HER2 positive tumors. Whether patients with small HER2-positive bc may be suitable for (chemo)therapy reduction strategies, the current available data cannot exclude the need for a more aggressive treatment in a small subset of these subjects. Novel clinical prognostic factors such as interval cancer (IC) detection may help to address this clinically important controversy. A multicenter population-based cancer registry study is currently evaluating whether IC detection may identify patients with pT1a N0M0 HER2-positive tumors in whom the rate of recurrence justifies consideration for use of conventional, trastuzumab-based chemotherapy regimens. PMID- 26827689 TI - Taxanes in the treatment of breast cancer: Have we better defined their role in older patients? A position paper from a SIOG Task Force. AB - Along with anthracyclines, taxanes are the most active cytotoxics in breast cancer (BC). Balancing efficacy against toxicity in older patients with reduced physiological reserves and significant comorbidities is both important and difficult. This is especially so given the under-representation of elderly patients in major trials and a consequent lack of evidence for drug, dose and schedule. However, BC is frequent in elderly women, who are a growing proportion of the population. Careful consideration of their care is therefore imperative. Treatment that can cure or extend the duration and quality of life should not be restricted by age, but needs to be tailored to the circumstances of elderly patients. In adjuvant use, taxane toxicity in older women is greater than in their younger counterparts, limiting its sequential combination with anthracyclines for high-risk disease unless patients are in very good health. More frequently taxanes are used alone (weekly paclitaxel, three-weekly docetaxel) or combined with cytotoxics other than anthracyclines (e.g. docetaxel plus cyclophosphamide) to reduce cardiac risk, especially in HER-2-positive patients who may develop additional trastuzumab-related cardiac events. In elderly patients with metastases, weekly paclitaxel and three-weekly docetaxel are among the cornerstones of treatment, with generally acceptable toxicity. Three-weekly docetaxel at the approved dose of 100mg/m(2) is not appropriate for the elderly. Nab-paclitaxel has efficacy comparable with solvent-based taxanes without need for steroid premedication but has been little studied in older BC patients. A head-to-head comparison with weekly paclitaxel favoured the solvent free formulation for pathologic response, but those studied were a general adult population. Compared with early stage disease, choice of taxane and regimen in the metastatic setting relies even more on availability and preferences with regard to schedule, toxicity profile and cost, especially for recently developed formulations. PMID- 26827688 TI - Targeting protein kinases to reverse multidrug resistance in sarcoma. AB - Sarcomas are a group of cancers that arise from transformed cells of mesenchymal origin. They can be classified into over 50 subtypes, accounting for approximately 1% of adult and 15% of pediatric cancers. Wide surgical resection, radiotherapy, and chemotherapy are the most common treatments for the majority of sarcomas. Among these therapies, chemotherapy can palliate symptoms and prolong life for some sarcoma patients. However, sarcoma cells can have intrinsic or acquired resistance after treatment with chemotherapeutics drugs, leading to the development of multidrug resistance (MDR). MDR attenuates the efficacy of anticancer drugs and results in treatment failure for sarcomas. Therefore, overcoming MDR is an unmet need for sarcoma therapy. Certain protein kinases demonstrate aberrant expression and/or activity in sarcoma cells, which have been found to be involved in the regulation of sarcoma cell progression, such as cell cycle, apoptosis, and survival. Inhibiting these protein kinases may not only decrease the proliferation and growth of sarcoma cells, but also reverse their resistance to chemotherapeutic drugs to subsequently reduce the doses of anticancer drugs and decrease drug side-effects. The discovery of novel strategies targeting protein kinases opens a door to a new area of sarcoma research and provides insight into the mechanisms of MDR in chemotherapy. This review will focus on the recent studies in targeting protein kinase to reverse chemotherapeutic drug resistance in sarcoma. PMID- 26827690 TI - AR-V7 and prostate cancer: The watershed for treatment selection? AB - The androgen receptor (AR) plays a key role in progression to metastatic castration-resistant prostate cancer (mCRPC). Despite the recent progress in targeting persistent AR activity with the next-generation hormonal therapies (abiraterone acetate and enzalutamide), resistance to these agents limits therapeutic efficacy for many patients. Several explanations for response and/or resistance to abiraterone acetate and enzalutamide are emerging, but growing interest is focusing on importance of AR splice variants (AR-Vs) and in particular of AR-V7. Increasing evidences highlight the concept that variant expression could be used as a potential predictive biomarker and a therapeutic target in advanced prostate cancer. Therefore, understanding the mechanisms of treatment resistance or sensitivity can help to achieve a more effective management of mCRPC, increasing clinical outcomes and representing a promising and engaging area of prostate cancer research. PMID- 26827691 TI - Second-line single-agent chemotherapy in human epidermal growth factor receptor 2 negative metastatic breast cancer: A systematic review. AB - BACKGROUND: No 'gold standard' exists for single-agent chemotherapy of human epidermal growth factor receptor 2-negative (HER2-negative) metastatic breast cancer (MBC) in the second-line. The objective of this systematic review is to identify and appraise overall survival (OS), progression-free survival (PFS), time to progression (TTP) and Grade >=3 adverse event evidence for single-agent chemotherapy in this setting. METHODS: MEDLINE, Embase and the Cochrane Library were searched to October 2013, and PubMed October 2013 to November 2014. Electronic database searches were supplemented with hand searching of reference lists and conferences. Eligible randomised controlled trials (RCTs) employed at least one single-agent chemotherapy treatment, enrolled HER2-negative or unselected MBC patients who had progressed following first-line chemotherapy within the metastatic setting, and reported outcomes of interest for the second line setting. RESULTS: Fifty-three RCTs were included in total, with most containing mixed populations by HER2 status and treatment line. Fourteen studies reported data specifically for second- and later-line treatment within the metastatic setting. Median overall survival (OS) in most trials was 8-13 months. Only one trial reported a significant difference between studied interventions in the second-line metastatic setting: nab-paclitaxel (n=131) conferred a statistically significant OS advantage vs. three-weekly paclitaxel (n=136) (median OS 13.0 vs. 10.7 months, respectively; hazard ratio 0.73, p=0.024) and improved overall safety. CONCLUSION: One RCT demonstrated significant benefit in this setting in confirmed HER2-negative MBC alongside favourable safety. Treatment line terminology was imprecise. To reliably inform patient treatment decisions, quality-of-life data are needed and precise OS estimation according to underlying patient characteristics. PMID- 26827692 TI - Window of opportunity studies: Do they fulfil our expectations? AB - Window of opportunity studies are trials in which patients receive one or more new compounds between their cancer diagnosis and standard treatment (mainly surgery). Patients are generally cancer treatment naive. Tumor biopsies before and after the investigational treatment are collected for translational research. Similarly, anatomic and functional pre- and post-treatment imaging may be incorporated. Ideally, the investigational treatment is kept short to avoid delaying standard treatment. Window of opportunity trials may expedite drug development, improve our understanding of pharmacodynamic parameters, and help to identify biomarkers for better patient selection. They can, however, have major drawbacks including potential safety and logistical issues, delayed standard treatment, and a probable lack of patient benefit. By focusing on breast and head and neck cancers, in this paper we discuss the advantages, disadvantages and design of window of opportunity studies. PMID- 26827693 TI - The safety profile of vorinostat (suberoylanilide hydroxamic acid) in hematologic malignancies: A review of clinical studies. AB - Histone acetyltransferases and histone deacetylases (HDACs) are multifunctional enzymes that posttranslationally modify both histone and nonhistone acetylation sites, affecting a broad range of cellular processes (e.g., cell cycle, apoptosis, and protein folding) often dysregulated in cancer. HDAC inhibitors are small molecules that directly interact with HDAC catalytic sites preventing the removal of acetyl groups, thereby counteracting the effects of HDACs. Since the first HDAC inhibitor, valproic acid, was investigated as a potential antitumor agent, there have been a number of other HDAC inhibitors developed to improve efficacy and safety. Despite significant progress in the management of patients with hematologic malignancies, overall survival is still poor. The discovery that HDACs may play a role in hematologic malignancies and preclinical studies showing promising activity with HDAC inhibitors in various tumor types, led to clinical evaluation of HDAC inhibitors as potential treatment options for patients with advanced hematologic malignancies. The Food and Drug Administration has approved two HDAC inhibitors, vorinostat (2006) and romidepsin (2009), for the treatment of cutaneous T-cell lymphoma. This review highlights the safety of HDAC inhibitors currently approved or being investigated for the treatment of hematologic malignancies, with a specific focus on the safety experience with vorinostat in cutaneous T-cell lymphoma. PMID- 26827694 TI - Evolution in the eligibility criteria of randomized controlled trials for systemic cancer therapies. AB - BACKGROUND: Eligibility criteria in randomized controlled trials (RCTs) reduce inter-patient heterogeneity, but may reduce generalizability of results. Here, we explore temporal changes in eligibility criteria of practice-changing RCTs for systemic cancer therapies and in the proportion of patients excluded from these trials after application of eligibility criteria. METHODS: An electronic search identified practice-changing RCTs published in six major journals between July 2010 and December 2012. Trial protocols were identified through journal websites and communication with authors or study sponsors. Eligibility criteria were extracted from protocols. The number of patients excluded after application of eligibility criteria was extracted from the CONSORT diagrams and text of publications. Changes in eligibility criteria over time were assessed by logistic regression and meta-regression was carried out to evaluate the impact of year of protocol on the proportion of patients who were excluded after screening. RESULTS: Eighty-six protocols written between 1987 and 2012 were included. Over time, there has been an increasing frequency of exclusion of patients with prior cerebrovascular events (OR 1.34, p=0.003), coagulation/bleeding disorders (OR 1.34, p=0.006), prior gastrointestinal bleeding (OR 1.33, p=0.01), cardiac co morbidities (OR 1.24, p=0.004) and exclusion based on concurrent medication (OR 1.19, p=0.01). There has been a decrease in upper age limit usage (OR 0.83, p=0.01) and leukopenia (OR 0.83, p=0.009). The proportion of patients excluded from trials has increased from 9% prior to 2000 to 18% after 2010 (p-value for trend <0.001). CONCLUSIONS: RCTs have become less representative of cancer patients treated in routine practice with increased use of organ-specific and co morbidity-based exclusion criteria. PMID- 26827695 TI - Clinical trial designs incorporating predictive biomarkers. AB - Development of oncologic therapies has traditionally been performed in a sequence of clinical trials intended to assess safety (phase I), preliminary efficacy (phase II), and improvement over the standard of care (phase III) in homogeneous (in terms of tumor type and disease stage) patient populations. As cancer has become increasingly understood on the molecular level, newer "targeted" drugs that inhibit specific cancer cell growth and survival mechanisms have increased the need for new clinical trial designs, wherein pertinent questions on the relationship between patient biomarkers and response to treatment can be answered. Herein, we review the clinical trial design literature from initial to more recently proposed designs for targeted agents or those treatments hypothesized to have enhanced effectiveness within patient subgroups (e.g., those with a certain biomarker value or who harbor a certain genetic tumor mutation). We also describe a number of real clinical trials where biomarker-based designs have been utilized, including a discussion of their respective advantages and challenges. As cancers become further categorized and/or reclassified according to individual patient and tumor features, we anticipate a continued need for novel trial designs to keep pace with the changing frontier of clinical cancer research. PMID- 26827696 TI - Therapy of leptomeningeal metastasis in solid tumors. AB - Leptomeningeal metastasis (LM), i.e. the seeding of tumor cells to the cerebrospinal fluid (CSF) and the leptomeninges, is a devastating and mostly late stage complication of various solid tumors. Clinical signs and symptoms may include cranial nerve palsies, radicular symptoms, signs of increased intracranial pressure such as headache, nausea and vomiting, and cognitive dysfunction. In cases of suspected LM, the highest diagnostic sensitivity is provided by the combination of CSF cytology and contrast-enhanced MRI (cranial as well as complete spine). The therapeutic spectrum includes radiotherapy of the clinically involved region as well as systemic and intrathecal chemotherapy. The choice of treatment modalities depends on the type of LM (non-adherent tumor cells in the CSF vs. nodular contrast-enhancing tumor growth), additional systemic involvement (uncontrolled vs. controlled systemic disease) and additional involvement of the CNS parenchyma (LM as the only CNS involvement vs. LM+parenchymal CNS metastases). Larger contrast-enhancing nodular LM or symptomatic lesions of the spine may be treated with radiotherapy. In case of uncontrolled systemic disease, the treatment regimen should include systemic chemotherapy. The choice of systemic treatment should take into account the histology of the primary tumor. Intrathecal chemotherapy is most important in cases of LM of the non-adherent type. There are three substances for routine use for intrathecal chemotherapy: methotrexate, cytarabine, and thiotepa. Liposomal cytarabine shows advantages in terms of longer injection intervals, a sufficient distribution in the entire subarachnoid space after lumbar administration and improved quality-of-life. The role of new agents (e.g. rituximab and trastuzumab) for intrathecal therapy is still unclear. PMID- 26827697 TI - Risk of subsequent gastrointestinal cancer among childhood cancer survivors: A systematic review. AB - BACKGROUND: Childhood cancer survivors (CCS) are at increased risk of developing subsequent malignant neoplasms, including gastrointestinal (GI) cancer. We performed a systematic review to summarize all available literature on the risk of, risk factors for, and outcome after subsequent GI cancer among CCS. METHODS: A systematic search of the literature databases Medline/PubMed (1945-2014) and Embase (1947-2014) was performed to identify studies that consisted of ?1000 CCS and assessed incidence of or mortality from subsequent GI cancer as an outcome. RESULTS: A total of 45 studies were included. Studies that reported risk measures for subsequent GI cancer compared to the general population showed a 3.2 to 9.7 fold elevated risk in cohort studies including all childhood cancer types. Abdominal radiotherapy was associated with an increased risk of subsequent GI cancer in all four studies that assessed this risk. Survivors who had received procarbazine and platinum agents were also suggested to be at increased risk. CONCLUSION: Abdominal radiotherapy is a risk factor for developing a subsequent GI cancer. Few studies examined detailed treatment-related risk factors and most studies had small number of GI cancer cases. Therefore, no conclusions could be drawn on the effect of time since childhood cancer on GI cancer risk and on outcome after a subsequent GI cancer. Additional research is necessary to further explore risk factors for and outcome after a subsequent GI cancer, and to systematically evaluate the harms and benefits of GI screening among high-risk survivors in order to give sound screening recommendations. PMID- 26827698 TI - Proton beams in cancer treatments: Clinical outcomes and dosimetric comparisons with photon therapy. AB - PURPOSE: To review current evidence of the role of proton therapy (PT) in other tumors than skull base, sinusal/parasinusal, spinal and pediatric tumors; to determine medico-economic aspects raised by PT. MATERIAL AND METHODS: A systematic review on Medline was performed with the following keywords: proton therapy, proton beam, protontherapy, cancer; publications with comparison between PT and photon-therapy were also selected. RESULTS: In silico studies have shown superiority (better dose delivery to the target and/or to organs at risk) of PT toward photon-therapy in most of thoracic and abdominal malignant tumors. Potential benefits of PT could be: reduction of toxicities (including radiation induced cancer), increase of tumor control through a dose-escalation approach, hypofractionation. Cost of treatment is always cited as an issue which actually can be managed by a precise patient selection making PT a cost-effective procedure. Comparison plan with photon therapy may be useful to determine the dosimetric and clinical advantages of PT (Normal Tissue Complications Probability). CONCLUSION: PT may be associated with a great advantage compared to the best photon-therapies in various types of cancers. Accumulation of clinical data is on-going and will challenge the in silico data analysis. Some indications are associated with strong superiority of PT and may be discussed as a new standard within prospective observational studies. PMID- 26827699 TI - Innovative perspectives of immunotherapy in head and neck cancer. From relevant scientific rationale to effective clinical practice. AB - It is now well established that head and neck cancer carcinogenesis is characterized by genetic instability and several immune defects, leading to unique host-tumor interactions. In such condition, recent improved comprehension and relevant findings could lead to identification of innovative molecular therapeutic targets, achieving considerable clinical and translational research. This review aims to summarize and to highlight most recent and relevant scientific rationale in this era of immunotherapy revival, and to correlate it to the near future clinical practice for the management of this challenging disease. PMID- 26827700 TI - Very few exclusive percepts for contrast-modulated stimuli during binocular rivalry. AB - Binocular rivalry properties for contrast-modulated (CM) gratings were examined to gain insight into their locus of processing. Two orthogonally orientated gratings were presented, one to each eye. Perceptual change rates, proportions of exclusivity and mixed percepts, and mean durations were calculated. Stimuli were noiseless luminance-defined (L), luminance-modulated noise (LM) and contrast modulated noise (CM) gratings with sizes of 1, 2 and 4deg and spatial frequencies of 4, 2 and 1c/deg, respectively. For the LM and CM gratings, binary noise was fully correlated between eyes. Maximum producible modulations were used (1.0 for CM, 0.78 for LM and 0.98 for L stimuli). In a control experiment, contrasts of LM gratings were reduced until the multiples over detection threshold were similar to those of CM stimuli. Trial durations of 120s were analyzed. Exclusive visibility decreased with increasing stimulus size regardless of the stimulus type. Even with visibilities at similar multiples above detection threshold, significantly lower proportions of exclusive percepts and perceptual changes were found for CM, compared to LM gratings. The results obtained with dichoptically presented orthogonal CM gratings are significantly different from those obtained for orthogonal gratings presented to one eye. CM stimuli therefore do engage in binocular rivalry but with different characteristics to those found for LM stimuli. These results suggest that CM stimuli are processed by a mechanism that promotes binocular combination rather than rivalry, and therefore may involve cells in a higher visual area than those that initially process LM information. PMID- 26827701 TI - Mean platelet volume predicts the glycemic control deterioration in diabetes mellitus type 2 patients. AB - AIM: To investigate association of mean platelet volume (MPV) and glycemic control markers, and whether MPV could be used as a predictor of deterioration of glucoregulation in Diabetes mellitus type 2 (DMT2) patients. METHODS: The cross sectional study included 106 DMT2 patients, treated at the Primary Health Care Centre in Zenica, distributed into groups according to glycated haemoglobin (HbA1c) values: A(n=44, HbA1c <=7.0%) and B (n=62, HbA1c>7.0%). Spearman's correlation coefficients were calculated to evaluate the relationships between MPV and glycemic control markers. Binomial logistic regression analysis was performed to estimate the relationship between glycemic control, as dichotomous outcome, and MPV as the main predictor. Diagnostic value of MPV as a marker for poor glucoregulation was estimated by using ROC analysis. RESULTS: Mean platelet volume was significantly higher in the group B compared to the group A (p<0.0005). Significant positive correlations of MPV with fasting blood glucose and HbA1c were found in the total sample (rho=0.382, p<0.0005; rho=0.430, p<0.0005, respectively). Mean platelet volume was positively associated with the risk of inadequate glycemic control, with 2 times increased odds of inadequate glycemic control per femtoliter greater MPV (Exp (beta) =2.195; 95% CI=1.468 - 3.282, p<0.0005). The area under ROC curve for MPV was 0.726 (95% CI: =0.628- 0.823, p <0.0005). At the best cut-off value 9.55 fL, MPV showed sensitivity of 82% and specificity of 54.5%. CONCLUSION: Mean platelet volume correlates with glycemic control markers in DMT2 patients. It could be used as a simple and cost effective predictor of deterioration of glucoregulation. PMID- 26827702 TI - Proenkefalin A and protachykinin in ischemic neurological complications after cardiac surgery. AB - AIM: The evaluation of biomarkers of acute ischemic brain injury following surgical revascularization of the heart with the use of the heart-lung machine (cardiopulmonary bypass, CPB). METHODS: Twenty consecutive patients were divided into two groups: the first 10 patients received a potential neuroprotective human recombinant erythropoietin, while the remaining 10 comprised the control group. Neurological complications were monitored by measuring serum concentrations of neuropeptide proenkephalin A(PENK-A) and protachykinin A (PTA) before and in the first 5 days after surgery, comparing the neurological outcome with MRI examinations. RESULTS: Both the erythropoietin-treated group and control group were comparable with a non-significant difference shown for the postoperative concentrations of PENK-A and PTA. A comparison of serum concentrations of the biomarkers of 16 patients without brain ischemia and 4 patients with acute ischemia also displayed no significant differences, regardless of erythropoietin therapy. CONCLUSION: In our pilot study the analysis of PENK-A and PTA serum concentrations might not be the strategy to enable the monitoring and evaluation of neuroprotective stroke treatment, but further studies are required to investigate its role in acute ischemic brain injury. PMID- 26827703 TI - Assessment of relation between neutrophil lympocyte, platelet lympocyte ratios and epicardial fat thickness in patients with ankylosing spondylitis. AB - AIM: To investigate whether there is a relation between neutrophillymphocyte (N/L) and platelet- lymphocyte (P/L) ratios and epicardial adipose tissue (EAT) thickness in patients with ankylosing spondylitis (AS). METHODS: Thirty patients diagnosed with ankylosing spondylitis and 25 healthy people (controls) were included in the study. Age, gender, body mass index (BMI), height, hemogram, sedimentation, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, CRP, hepatic and renal function tests, lipid profile of the all patients were recorded. Data related to duration of the disease, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) values of the cases in the patient group were obtained. A cardiologist measured EAT thickness by ECHO in both patient and control groups. RESULTS: In the patient group, mean BASDAI and BASFI scores were 2.48+/-2.21 and 1.5+/-2.07, respectively. Age, gender, BMI values did not show statistically significant difference between the patient and the control groups. N/L and P/L ratios did not change significantly in the patient group having higher EAT, BASFI values and taking anti-TNF compared to the control group. CONCLUSION: In patients with AS, EAT measurements, which are related to inflammatory response increase, can be used for monitoring of the risk of development of cardiac disease. We could not find the relation between EAT and N/L, P/L ratios in terms of evaluation of inflammatory response. PMID- 26827704 TI - A thin line between Meniere's disease and spontaneous intracranial hypotension syndrome. AB - AIM: To point out the similarity of Meniere disease and spontaneous intracranial hypotension and difference of their treatment. METHODS: A case of a 54-year-old male patient with previously diagnosed Meniere's disease and newly diagnosed spontaneous intracranial hypotension syndrome is presented. Additional neuroradiological examination, Brain contrast-enhanced MRI and MR myelography were used for diagnosis. RESULTS: Due to deterioration of vertigo, hearing loss and tinnitus in the right ear the patient was referred to the additional neuroradiological examination which confirmed the diagnosis of spontaneous intracranial hypotension syndrome. Brain contrast-enhanced MRI showed increased pachymeningeal contrast enhancement, and MR myelography identified the location of CSF leak. The patient was successfully treated conservatively. CONCLUSION: According to our knowledge this is the fifth case report of Meniere's disease and spontaneous intracranial hypotension coexistence. Both diseases have similar clinical presentation and initial treatment. We suggest procedures of additional examination when the treatment fails and initial diagnosis becomes questionable. PMID- 26827705 TI - Can a finding of cervical vestibular evoked myogenic potentials contribute to vestibular migraine diagnostics? AB - AIM: To investigate differences in vestibular evoked myogenic potentials (VEMP) results with patients suffering from vestibular migraine and healthy people, taking into consideration values of threshold and latency of occurrence of the characteristic wave complex, size of amplitude, and interaural amplitude ratio. According to the results, determine the importance and usefulness of VEMP in vestibular migraine diagnostics. METHODS: A total number of 62 subjects were included in the study, 32 of them belonging to a group of patients suffering from vestibular migraine (VM), while other 30 were in a control group of healthy subjects. Information was collected during the diagnostic evaluation. General and otoneurological history of patients and bedside tests, audiological results, videonystagmography and cervical vestibular evoked myogenic potentials (cVEMP) were made. RESULTS: There was a difference in an interaural ratio of amplitudes in the experimental and control groups, but it was not found to be clinically significant. By ToneBurst 500 Hz method, the interaural amplitude ratio higher than 35% was measured in 46.97% subjects, while the response was totally unilaterally missing in 28.8% patients. CONCLUSION: Even the sophisticated method as cVEMP does not give the ultimate result confirming the vestibular migraine diagnosis, and neither do other diagnostic methods. cVEMP result can contribute to the completion of full mosaic of vestibular migraine diagnostics. PMID- 26827706 TI - Depression during multiple sclerosis relapse: relation to disability and relapse severity. AB - AIM: To examine the presence of depressive symptoms in patients with multiple sclerosis relapse and its relation to disability and relapse severity. METHODS: This study included 120 patients who were assessed during the acute relapse of multiple sclerosis according to Mc Donald criteria. Depression was assessed using Beck Depression Inventory II (BDI-II) calculating both affective and somatic symptom scores. The Expanded Disability Status Scale (EDSS) measured disability. Relapse severity was graded according to the difference between the EDSS score during relapse and EDSS score before the onset of the attack as mild, moderate or severe. RESULTS: There was statistically significant difference between patients with different level of depression considering age (p<0.001), disability (p<0.001), relapse severity (p=0.005) and disease duration (p=0.032). Significant moderate positive correlation of depression with age (rho=0.43) and disability (rho=0.46) was confirmed. There was moderate correlation between disability and somatic symptoms of depression (rho=0.54, p<0.001) with only weak correlation between disability and affective symptoms of depression (rho=0.31, p<0.01). Multiple regression analysis showed that patient's age and relapse severity (p<0.05) were independently related to depression in these patients while disability did not. CONCLUSION: Correlation between disability and depression was mostly due to somatic symptoms of depression. Although highly correlated, depression during multiple sclerosis relapse was not independently predicted by disability. Depression should be recognized and treated independently from disability treatment, especially in the group of older patients with more severe relapse. PMID- 26827707 TI - Does odor and taste identification change during hyperemesis gravidarum? AB - AIM: To investigate a difference in odor and taste identification among pregnant women with hyperemesis gravidarum, those with healthy pregnancy and non-pregnant women. METHODS: This prospective, controlled study included 33 pregnant women with hyperemesis gravidarum, 33 healthy pregnant and 26 non-pregnant women. For all participants, rhinological examinations were performed. Odor and taste identification were performed by holding Sniffin' Sticks test battery (Burghart, Wedel, Germany) in all participants. RESULTS: There was a statistically significant difference in results of odor identification tests among the groups (p=0.031). Rose odor was selected as the most pleasant odor by the hyperemesis gravidarum group, 32 (96.9%). Orange odor was selected as the most pleasant odor by the healthy pregnant women, 33 (100%) whereas the banana odor was selected as the most pleasant odor by the healthy non-pregnant women, 10 (38.4%). In taste identification tests, there was a significant difference in total taste scores among the groups (p=0.003). CONCLUSION: It is obvious that there is a need to evaluate odor thresholds and other parameters by detailed studies on odor perception in the context of hyperemesis gravidarum. PMID- 26827708 TI - Mucilaginibacter carri sp. nov., isolated from a car air conditioning system. AB - A Gram-stain-negative, pink bacterial strain, designated PR0008KT, was isolated from an automobile evaporator core in Korea. The cells were obligately aerobic and rod-shaped. The strain grew at 10-40 degrees C (optimum, 20 degrees C), at pH 5-8 (optimum, 7), and in the presence of 0-1.5% (w/v) NaCl. Phylogenetically, the strain was closely related to members of the genus Mucilaginibacter (93.4 97.0% 16S rRNA sequence similarities) and showed a high sequence similarity with Mucilaginibacter litoreus BR-18T, Mucilaginibacter lutimaris BR-3T and Mucilaginibacter soli R9-65T (97.0%, 96.9% and 96.9% 16S rRNA sequence similarity, respectively). It contained summed feature 3 (C16:1omega7c and/or C16:1omega6c), C16 : 0, iso-C17:0 3-OH and C16:0 as the predominant fatty acids and MK-7 as the major menaquinone. The polar lipids were phosphatidylethanolamine, one unknown aminophospholipid, two unknown aminolipids and two unknown polar lipids. The DNA G+C content of this strain was 47.4 mol%. Based on the phenotypic, genotypic and chemotaxonomic data, strain PR0008KT represents a novel species in the genus Mucilaginibacter, for which the name Mucilaginibacter carri sp. nov. (=KACC 17938T=NBRC 111539T) is proposed. PMID- 26827709 TI - Gender differences in irritable bowel syndrome among medical students at Inner Mongolia Medical University, China: a cross-sectional study. AB - There is little epidemiological research on Irritable bowel syndrome (IBS) in Inner Mongolia, China. Here we investigated the prevalence of IBS and factors associated with IBS in both males and females in Inner Mongolia Medical University by a cross-sectional study. We recruited Inner Mongolia Medical University students residing in campus and asked them to complete a self administered questionnaire. The prevalence of IBS in each factor we chose in all, male, and female students was determined. We assessed IBS subtypes in male and female students. Multivariate logistic regression models were used to assess the factors associated with IBS in male and female students. The overall prevalence of IBS was 29.5%. The prevalence of IBS in female students was significantly higher than that in male students (31.3% vs. 24.8%, p < .001). Logistic regression results showed that attempting to lose weight and anxiety were both associated with increasing odds of IBS, while exercise was not associated with IBS in either male or female students. In female students, snack consumption and depression were also both associated with increasing odds of IBS. The predominant IBS subtype was the diarrhea-predominant type in both male and female students. Considering the high prevalence of IBS in students and the fact that the factors associated with IBS can be improved by individuals, students should be given adequate education and counseling to improve their mental health and lifestyle, especially female students in higher grades. PMID- 26827710 TI - Pontibacter amylolyticus sp. nov., isolated from a deep-sea sediment hydrothermal vent field. AB - A Gram-stain-negative, short rod-shaped bacterium, designated 9-2T, was isolated from a sediment sample collected from a hydrothermal vent field on the south-west Indian Ridge. It formed red colonies, produced carotenoid-like pigments and did not produce bacteriochlorophyll a. Strain 9-2T was positive for hydrolysis of DNA, gelatin and starch, but negative for hydrolysis of aesculin and Tween 60. The sole respiratory quinone was menaquinone-7 (MK-7). The main polar lipids consisted of phosphatidylethanolamine, one unidentified phospholipid and two unidentified polar lipids. The principal fatty acids (>5%) were summed feature 4 (iso-C17:1 I and/or anteiso-C17:1 B), iso-C15:0 and iso-C17:0 3-OH. The genomic DNA G+C content was 49.2 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 9-2T should be assigned to the genus Pontibacter. Levels of 16S rRNA gene sequence similarity between the new isolate and the type strains of Pontibacter species with validly published names were in the range 94.0-96.5%. On the basis of phenotypic and genotypic data, strain 9-2T represents a novel species of the genus Pontibacter, for which the name Pontibacter amylolyticus sp. nov. is proposed. The type strain is 9-2T (=CGMCC 1.12749T=JCM 19653T=MCCC 1K00278T). PMID- 26827711 TI - Cell membranes: A subjective perspective. AB - Cell membranes have developed a tremendous complexity of lipids and proteins geared to perform the functions cells require. The lipids have for long remained in the background and are now regaining their role as important building blocks of cells. Their main function is to form the matrix of our cell membranes where they support a variety of functions essential for life. This 2-dimensional fluid matrix has evolved unexpected material properties that involve both lipid-lipid and lipid-protein interactions. This perspective is a short summary of the challenges that this field faces and discusses potential ways and means for coming to grips with the properties of this incredible fluid. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Rog. PMID- 26827713 TI - What initial oxygen is best for preterm infants in the delivery room?-A response to the 2015 neonatal resuscitation guidelines. PMID- 26827714 TI - Frequency of dressing changes for central venous access devices on catheter related infections. AB - BACKGROUND: People admitted to intensive care units and those with chronic health care problems often require long-term vascular access. Central venous access devices (CVADs) are used for administering intravenous medications and blood sampling. CVADs are covered with a dressing and secured with an adhesive or adhesive tape to protect them from infection and reduce movement. Dressings are changed when they become soiled with blood or start to come away from the skin. Repeated removal and application of dressings can cause damage to the skin. The skin is an important barrier that protects the body against infection. Less frequent dressing changes may reduce skin damage, but it is unclear whether this practice affects the frequency of catheter-related infections. OBJECTIVES: To assess the effect of the frequency of CVAD dressing changes on the incidence of catheter-related infections and other outcomes including pain and skin damage. SEARCH METHODS: In June 2015 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. We also searched clinical trials registries for registered trials. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: All randomised controlled trials (RCTs) evaluating the effect of the frequency of CVAD dressing changes on the incidence of catheter-related infections on all patients in any healthcare setting. DATA COLLECTION AND ANALYSIS: We used standard Cochrane review methodology. Two review authors independently assessed studies for inclusion, performed risk of bias assessment and data extraction. We undertook meta-analysis where appropriate or otherwise synthesised data descriptively when heterogeneous. MAIN RESULTS: We included five RCTs (2277 participants) that compared different frequencies of CVAD dressing changes. The studies were all conducted in Europe and published between 1995 and 2009. Participants were recruited from the intensive care and cancer care departments of one children's and four adult hospitals. The studies used a variety of transparent dressings and compared a longer interval between dressing changes (5 to15 days; intervention) with a shorter interval between changes (2 to 5 days; control). In each study participants were followed up until the CVAD was removed or until discharge from ICU or hospital. Confirmed catheter-related bloodstream infection (CRBSI)One trial randomised 995 people receiving central venous catheters to a longer or shorter interval between dressing changes and measured CRBSI. It is unclear whether there is a difference in the risk of CRBSI between people having long or short intervals between dressing changes (RR 1.42, 95% confidence interval (CI) 0.40 to 4.98) (low quality evidence). Suspected catheter related bloodstream infection Two trials randomised a total of 151 participants to longer or shorter dressing intervals and measured suspected CRBSI. It is unclear whether there is a difference in the risk of suspected CRBSI between people having long or short intervals between dressing changes (RR 0.70, 95% CI 0.23 to 2.10) (low quality evidence). All cause mortalityThree trials randomised a total of 896 participants to longer or shorter dressing intervals and measured all cause mortality. It is unclear whether there is a difference in the risk of death from any cause between people having long or short intervals between dressing changes (RR 1.06, 95% CI 0.90 to 1.25) (low quality evidence). Catheter site infectionTwo trials randomised a total of 371 participants to longer or shorter dressing intervals and measured catheter-site infection. It is unclear whether there is a difference in risk of catheter-site infection between people having long or short intervals between dressing changes (RR 1.07, 95% CI 0.71 to 1.63) (low quality evidence). Skin damage One small trial (112 children) and three trials (1475 adults) measured skin damage. There was very low quality evidence for the effect of long intervals between dressing changes on skin damage compared with short intervals (children: RR of scoring >= 2 on the skin damage scale 0.33, 95% CI 0.16 to 0.68; data for adults not pooled). PainTwo studies involving 193 participants measured pain. It is unclear if there is a difference between long and short interval dressing changes on pain during dressing removal (RR 0.80, 95% CI 0.46 to 1.38) (low quality evidence). AUTHORS' CONCLUSIONS: The best available evidence is currently inconclusive regarding whether longer intervals between CVAD dressing changes are associated with more or less catheter related infection, mortality or pain than shorter intervals. PMID- 26827712 TI - Keloids: Animal models and pathologic equivalents to study tissue fibrosis. AB - Animal models are crucial for the study of fibrosis. Keloids represent a unique type of fibrotic scarring that occurs only in humans, thus presenting a challenge for those studying the pathogenesis of this disease and its therapeutic options. Here, several animal models of fibrosis currently in use are described, emphasizing recent progress and highlighting encouraging challenges. PMID- 26827715 TI - Effect of mutated defensin NP-1 on sciatic nerve regeneration after transection- A pivot study. AB - Defensins are small cationic peptides that constitute the first line of defense against pathogens and are involved in immune regulation. In this study, their role in peripheral nerve regeneration was investigated. Rat sciatic nerves were transected and the two nerve stumps were bridged by a chitin conduit with a gap of 5mm between the stumps. The animals were injected intramuscularly with mutated rabbit neutrophil peptide 1 (defensin mNP-1), the positive control nerve growth factor (NGF) or the negative control saline, for 7 consecutive days after repair. After 6 weeks, the sciatic functional index (SFI), MNCV (motor nerve conductive velocity) and morphological parameters including myelinated fiber amounts, fiber diameter, axon diameter, myelin thickness and G-ratio were measured. Compared to the SFI of saline group, the NGF and mNP-1 groups had an increase of 18.3% and 18.8%, respectively. The numbers of myelinated fibers in the distal nerve of NGF and mNP-1 groups were 1.45- and 1.32-fold higher than in the saline group. The MNCVs of NGF and mNP-1 groups were 7.3 and 4.4 times of that of saline group. Fiber diameter, axon diameter, myelin thickness and G-ratio in the NGF and mNP-1 groups were also significantly higher than those of saline group. Our results demonstrate that, like NGF, the defensin mNP-1 can promote regeneration after a peripheral nerve cut. PMID- 26827716 TI - Neuroprotective effects of stemazole in the MPTP-induced acute model of Parkinson's disease: Involvement of the dopamine system. AB - Parkinson's disease is a neurodegenerative disorder characterized by a loss of nigrostriata dopaminergic neurons, which has been thought, at least in part, to result from oxidative stress. The present study aims to investigate the neuroprotective effects of stemazole (ST) on the dopamine (DA) system and its possible mechanisms of action in a mouse model of PD. Mice were injected intraperitoneally with MPTP (20mg/kg) four times at 2-h intervals for one day to induce Parkinsonism, and then treated with ST (10, 30 and 50mg/kg) or Madopar (120mg/kg) for 7days. Behavioral analyses were performed with locomotor activity measures and rotarod test. Tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels were detected by immunohistochemistry method. DA and its metabolites were determined by high-performance liquid chromatography with an electrochemical detector. Oxidative stress levels were assessed by measuring the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). Our results demonstrated that ST treatment improved locomotor activity and motor coordination in MPTP mice. There was also a significant increase in TH-positive cells (~24%, P<0.01) and DAT levels (~26%, P<0.01) in MPTP mice treated with ST (50mg/kg) compared with the vehicle group. Madopar treatment showed weaker effects on TH positive cells (~21%, P<0.05) and DAT levels (~21%, P<0.05). DA and its metabolite levels were significantly increased with ST (50mg/kg) treatment (P<0.01, compared with the vehicle group). In addition, SOD and GSH-PX activities were elevated notably in ST treatment groups compared with the vehicle group. In conclusion, these results suggest that ST has neuroprotective effect on the impaired DA system, potentially through enhancement of the cell's anti-oxidative capacity. Hence it may be used as a potential therapeutic agent for Parkinson's disease. PMID- 26827718 TI - Translational otolith-ocular reflex during off-vertical axis rotation in humans. AB - Two characteristics of otolith-ocular responses - linear vestibulo-ocular reflex and vergence - were examined during constant velocity off-vertical axis rotation (OVAR) in the dark. Sixteen subjects were rotated about their longitudinal axis when tilted 30 degrees relative to the direction of gravity. Rotational velocities were 36 and 288/s corresponding to frequencies of 0.1 and 0.8Hz, respectively. Subjects were asked to imagine stationary targets located at 0.5m, 1m, and 2m in the straight-ahead direction. Binocular eye movements were recorded in the dark using infrared videography. The modulation of horizontal slow phase velocity during OVAR was larger at 0.8Hz than at 0.1Hz, and the modulation at the high frequency was larger for the near target than for the mid and far targets. These characteristics confirm that the horizontal slow phase velocity during yaw OVAR represents a translational otolith-ocular reflex in response to acceleration along the inter-aural axis that is dependent on imagined fixation distance. PMID- 26827717 TI - Sulfated polysaccharide isolated from the sea cucumber Stichopus japonicas promotes the SDF-1alpha/CXCR4 axis-induced NSC migration via the PI3K/Akt/FOXO3a, ERK/MAPK, and NF-kappaB signaling pathways. AB - The present study describes a positive regulatory loop between SJP and the SDF 1alpha/CXCR4 axis in NSC migration. The treatment of NSCs with SJP and SDF-1alpha increases the cell migration capacity and promotes cell migration from the neurospheres. These effects are accompanied by the up-regulation of Nestin, N cadherin, TLR4, TNF-alpha, Cyclin D1, EGFR, Alpha 6 integrin, MMP-2, MMP-9, and iNOS, including SDF-1alpha and CXCR4 themselves. However, these effects are blocked by AMD3100, LY294002, U0126, and PDTC. SJP enhances the SDF-1alpha/CXCR4 axis-induced MMP-2 and MMP-9 secretion and NO release. Results demonstrate that interaction of SJP with the SDF-1alpha/CXCR4 axis regulates NSC migration via the PI3K/Akt/FOXO3a, ERK-MAPK, and NF-kappaB signaling pathways. PMID- 26827719 TI - The ventral tegmental area modulates intracortical microstimulation (ICMS)-evoked M1 activity in a time-dependent manner. AB - Intracortical microstimulation (ICMS)-evoked neural activity combined with ventral tegmental area (VTA) stimulation was studied in rat primary motor cortex (M1). We used voltage-sensitive dye (VSD) imaging to analyze the spatiotemporal dynamics of M1 activity following VTA-M1 paired stimulation. VTA stimulation was preceded by M1 ICMS at inter-stimulus intervals (ISIs) of 15-350ms. VSD imaging showed an excitatory-inhibitory sequence of neural activity after composing VTA stimulus- and ICMS-induced M1 neural activity. To evaluate the net ICMS M1 response, the optical response to unpaired VTA stimulation was subtracted from the VTA-M1 paired response. This revealed that the net ICMS-evoked M1 neural activity was inhibited when the ISI was 30-50ms, but highly facilitated when the ISI was 100-350ms. These results suggest that VTA modulates M1 excitability in the order of tens to hundreds of milliseconds and might directly affect the motor command generation process in the M1. PMID- 26827720 TI - The inactivation of extracellular signal-regulated kinase by glucagon-like peptide-1 contributes to neuroprotection against oxidative stress. AB - Glucagon-like peptide-1 (GLP-1), an insulinotropic peptide secreted from enteroendocrine cells, has been known to have a neuroprotective effect. However, it is not fully understood the intracellular mediator of GLP-1 signaling in neuronal cells. In the present study, we examined the change in intracellular signaling of cortical neurons after GLP-1 application and luminal glucose stimulation in vitro and in vivo. GLP-1 receptor was highly expressed in cultured cortical neurons and brain tissues including the prefrontal cortex and hippocampus. The activation of GLP-1 receptor (5min) significantly decreased levels of phosphorylated extracellular signal-regulated kinase (pERK), which is involved in neuronal cell survival and death, in cultured cortical neurons. Oral glucose administration also rapidly reduced pERK levels in the prefrontal cortex, while intraperitoneal glucose injection did not show such an effect. Further, GLP 1 attenuated hydrogen peroxide-induced cell death and hyperactivity of ERK in cultured cortical neurons. It is possible that increased GLP-1 by luminal glucose stimulation affects cortical system including the maintenance of neuronal cell survival. PMID- 26827721 TI - Central anti-fatigue activity of verbascoside. AB - In this study, the effects of verbascoside on treadmill exercise endurance, 5 hydroxytryptamine (5-HT) concentrations, the second isoforms of tryptophan hydroxylase (TPH2) and serotonergic type 1B inhibitory autoreceptors (5-HT1B) protein expression in the caudate putamen of exercised rats were investigated. Sixty Sprague-Dawley male rats were randomly divided into six groups: normal group, exercise group, exercise and verbascoside (0.1mg/kg)-treated group, exercise and verbascoside (1mg/kg)-treated group, exercise and verbascoside (10mg/kg)-treated group, exercise and caffeine (10mg/kg)-treated group. In exercise groups, rats were put on treadmill and forced to run for 30min once a day for 6 consecutive days. On the 7th day of the experiment, the time to exhaustion in treadmill exercise was determined for the trained groups. Immediately after the determination of the exhaustion time, all rats were sacrificed. 5-HT concentrations were detected by HPLC analysis. TPH2 and 5-HT1B protein expression were measured by western blot analysis. We found that verbascoside could prolong the time to exhaustion in treadmill exercise and suppress the exercise-induced increase of 5-HT synthesis and TPH2 protein expression, and prevent the exercise-induced decrease of 5-HT1B protein expression in the caudate putamen. Verbascoside was found as effective as caffeine in these effects. Verbascoside at 10mg/kg improved endurance of exercised rats. The mechanism of verbascoside' s anti-fatigue activity might be related to the inhibition of the exercise-induced synthesis of 5-HT and TPH2 expression, and to the increase of the 5-HT1B expression in the caudate putamen of exercised rats. PMID- 26827722 TI - Rolandic beta-band activity correlates with decision time to move. AB - Research findings link rolandic beta-band activity to voluntary movements, but a linkage with the decision time to move remains unknown. We found that beta-band (16-28Hz) activity shortly before the movement onset is relevant for the decision time to move: the more pronounced the decrease in beta-band synchronization, the earlier the subjective experience of the decision to move. The linkage was relevant regarding 'decision', but not regarding 'intention' timing that has been often applied in the study of free will. Our findings suggest that oscillatory neural activity in the beta-band is an important neural signature pertaining to the subjective experience of making a decision to move. PMID- 26827724 TI - Ribosome Induces a Closed to Open Conformational Change in Release Factor 1. AB - Bacterial translation termination is triggered when a stop codon arrives at the ribosomal A site. Stop codons are recognized by class I release factors (RF1 and RF2 in Escherichia coli), which bind to the ribosome and catalyze the release of the newly synthesized protein. Crystal structures showed that RF1 and RF2 are in an open conformation when bound to the ribosome but are in a closed conformation when not bound to the ribosome. It is not clear whether only the open form of RF1 and RF2 binds to the ribosome. Alternatively, the closed form of RF1 and RF2 may bind to the ribosome and undergo a conformational change to the open state upon binding. We used transition metal ion fluorescence resonance energy transfer experiments to monitor precisely the conformation of RF1 in the absence and presence of the ribosome. Our results indicate that RF1 undergoes a large conformational change from a closed to an open form upon binding to the ribosome. Our results are consistent with the mechanism, in which high termination fidelity is achieved by linking stop codon recognition by RF1 to the change in conformation from closed to open state. PMID- 26827723 TI - Alteration of nuclear factor-kappaB pathway promote neuroinflammation depending on the functions of estrogen receptors in substantia nigra after 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine treatment. AB - The simultaneous role of neuroprotective estrogen and neurodegenerative inflammation during the progression of Parkinson's disease (PD) is still remaining elusive. The novel importance of the present study in MPTP mediated mouse model of Parkinson's disease (PD) is-to investigate the status of neuronal and glial cells in a time chase experiment; to explore which pathway of NF-kappaB exist to proceed the neuroinflammation; to investigate the status of estrogen and the activation pattern of nuclear or cytosolic estrogen receptors in either sexes of Swiss albino mice during MPTP mediated progressive neurodegeneration in the substantia nigra. After MPTP intoxication, the nigral molecular anatomy was changed differently in separate time interval during the progression of neurodegeneration with/without association of glial cells and functional (via its nuclear and cytosolic receptors) estrogen level. Both the canonical and/or non canonical pathways of NF-kappaB exist in the substantia nigra of both the sexes after MPTP treatment that is why inspite of presence of estrogen, neuroinflammation progresses. The homodimeric or heterodimeric form of ER-beta binds with NF-kappaB molecules p65 and RelB differently, but the canonical or non canonical pathways of NF-kappaB molecules could not be stopped or may be promoted. PMID- 26827726 TI - The Era of Synthetic Biology and Genome Engineering: Where No Man Has Gone Before. PMID- 26827727 TI - A Stable Mutant Predisposes Antibody Domains to Amyloid Formation through Specific Non-Native Interactions. AB - The aggregation of mostly antibody light chain variable (VL) domains into amyloid fibrils in various tissues is the main cause of death in systemic amyloid light chain amyloidosis. Point mutations within the domain are important to shift the VL into the fibrillar pathway, but why and how only some site-specific mutations achieve this still remains elusive. We show here that both destabilizing and surprisingly stable mutants readily predispose an amyloid-resistant VL domain to amyloid formation. The decreased thermodynamic stability of the destabilizing mutant results in the accumulation of non-native intermediates that readily populate the amyloid state. Interestingly, the stable mutants establish site specific non-native interactions with especially nearby serine/threonine residues that unexpectedly do not affect the folding behavior of the VL domain but rather readily induce and stabilize the fibril structure, a previously unrecognized mechanism. These findings provide a new concept for the molecular mechanism of amyloid fibril formation. PMID- 26827728 TI - Protein Import by the Mitochondrial Presequence Translocase in the Absence of a Membrane Potential. AB - The highly organized mitochondrial inner membrane harbors enzymes that produce the bulk of cellular ATP via oxidative phosphorylation. The majority of inner membrane protein precursors are synthesized in the cytosol. Precursors with a cleavable presequence are imported by the presequence translocase (TIM23 complex), while other precursors containing internal targeting signals are imported by the carrier translocase (TIM22 complex). Both TIM23 and TIM22 are activated by the transmembrane electrochemical potential. Many small inner membrane proteins, however, do not resemble canonical TIM23 or TIM22 substrates and their mechanism of import is unknown. We report that subunit e of the F1Fo ATP synthase, a small single-spanning inner membrane protein that is critical for inner membrane organization, is imported by TIM23 in a process that does not require activation by the membrane potential. Absence of positively charged residues at the matrix-facing amino-terminus of subunit e facilitates membrane potential-independent import. Instead, engineered positive charges establish a dependence of the import reaction on the electrochemical potential. Our results have two major implications. First, they reveal an unprecedented pathway of protein import into the mitochondrial inner membrane, which is mediated by TIM23. Second, they directly demonstrate the role of the membrane potential in driving the electrophoretic transport of positively charged protein segments across the inner membrane. PMID- 26827729 TI - A nanopatterned cell-seeded cardiac patch prevents electro-uncoupling and improves the therapeutic efficacy of cardiac repair. AB - The heart is an extremely sophisticated organ with nanoscale anisotropic structure, contractility and electro-conductivity; however, few studies have addressed the influence of cardiac anisotropy on cell transplantation for myocardial repair. Here, we hypothesized that a graft's anisotropy of myofiber orientation determines the mechano-electrical characteristics and the therapeutic efficacy. We developed aligned- and random-orientated nanofibrous electrospun patches (aEP and rEP, respectively) with or without seeding of cardiomyocytes (CMs) and endothelial cells (ECs) to test this hypothesis. Atomic force microscopy showed a better beating frequency and amplitude of CMs when cultured on aEP than that from cells cultured on rEP. For the in vivo test, a total of 66 rats were divided into six groups: sham, myocardial infarction (MI), MI + aEP, MI + rEP, MI + CM-EC/aEP and MI + CM-EC/rEP (n >= 10 for each group). Implantation of aEP or rEP provided mechanical support and thus retarded functional aggravation at 56 days after MI. Importantly, CM-EC/aEP implantation further improved therapeutic outcomes, while cardiac deterioration occurred on the CM EC/rEP group. Similar results were shown by hemodynamic and infarct size examination. Another independent in vivo study was performed and electrocardiography and optical mapping demonstrated that there were more ectopic activities and defective electro-coupling after CM-EC/rEP implantation, which worsened cardiac functions. Together these results provide comprehensive functional characterizations and demonstrate the therapeutic efficacy of a nanopatterned anisotropic cardiac patch. Importantly, the study confirms the significance of cardiac anisotropy recapitulation in myocardial tissue engineering, which is valuable for the future development of translational nanomedicine. PMID- 26827725 TI - Various Themes of Myosin Regulation. AB - Members of the myosin superfamily are actin-based molecular motors that are indispensable for cellular homeostasis. The vast functional and structural diversity of myosins accounts for the variety and complexity of the underlying allosteric regulatory mechanisms that determine the activation or inhibition of myosin motor activity and enable precise timing and spatial aspects of myosin function at the cellular level. This review focuses on the molecular basis of posttranslational regulation of eukaryotic myosins from different classes across species by allosteric intrinsic and extrinsic effectors. First, we highlight the impact of heavy and light chain phosphorylation. Second, we outline intramolecular regulatory mechanisms such as autoinhibition and subsequent activation. Third, we discuss diverse extramolecular allosteric mechanisms ranging from actin-linked regulatory mechanisms to myosin:cargo interactions. At last, we briefly outline the allosteric regulation of myosins with synthetic compounds. PMID- 26827731 TI - Letter From the Guest Editor: Radiological Imaging of Alimentary Tract Perforations. PMID- 26827730 TI - Galectin expression in healing wounded skin treated with low-temperature plasma: Comparison with treatment by electronical coagulation. AB - Low-temperature plasma is useful for the care of wounded skin. It accelerates wound healing. However, the mechanism of this effect has not been fully elucidated yet. Galectin-1 is reported to accelerate wound healing via the Smad signaling pathway. In the present study to clarify whether or not galectins were expressed during the process of wound healing in the plasma-treated skin, we examined the effect of low-temperature plasma on galectin expression in the healing skin. We compared the effects of low-temperature plasma on the expression of galectin-1, -2, and -3 in the healing skin with those of electrocoagulation conducted with a high-frequency electrical coagulator. Immediately after the start of low-temperature plasma treatment following the incision made in the skin, a membrane-like structure was formed on the surface of the wound. Immunoelectron microscopy showed that these galectins were localized in the membrane-like structure of the plasma-treated skin. The expressions of these galectins were increased by the low-temperature plasma treatment, whereas they were inhibited by the electrocoagulation. These results suggest that galectins were involved in the wound healing of low-temperature plasma-treated skin. Galectins will thus be good markers for further examination of the effects of low temperature plasma on the healing of wounded skin. PMID- 26827732 TI - Spectrum of Signs of Pneumoperitoneum. AB - Pneumoperitoneum is caused by rupture of a hollow viscus that includes the stomach, small bowel, and large bowel, with the exception of those portions that are retroperitoneal in the duodenum and colon. The causes of pneumoperitoneum are numerous, ranging from iatrogenic and benign causes to more life-threatening conditions. In the absence of a benign cause of pneumoperitoneum, the identification of free intraperitoneal gas usually indicates the need for emergency surgery to repair a perforated bowel. The plain film is the primary diagnostic tool for detecting pneumoperitoneum: multiple signs of free intraperitoneal air can be found especially on supine abdominal radiographs. Computed tomography (CT) examination has been shown to be more sensitive than abdominal radiographs for the detection of free intraperitoneal air. It is important that the radiologist become familiar with the signs of pneumoperitoneum that can be discerned on abdominal radiographs, on CT scout view, and on CT scan. PMID- 26827733 TI - Multidetector Computed Tomography of Pharyngo-Esophageal Perforations. AB - Perforation of the esophagus remains a diagnostic and therapeutic challenge. Currently, the most common cause of perforation is instrumentation of the esophagus, but other conditions such as foreign body, trauma, or spontaneous rupture are possible entities in the clinical practice. Multidetector computed tomography has become the imaging technique of choice in the evaluation of this setting of patients because of its capability to depict all the different signs associated with the degrees of wall impairment. By being aware of the appearance of the various entities that affect the esophagus, the radiologist can play an important role in detecting and staging esophageal injuries. PMID- 26827734 TI - Imaging Assessment of Gastroduodenal Perforations. AB - Gastroduodenal perforation is an emergency situation that usually requires early recognition and well-timed surgical treatment. It can arise from different natural, iatrogenic, or traumatic causes, and it can present with various symptoms especially in the early phase. This article reviews the role of the different imaging techniques in the diagnosis of gastroduodenal perforation, focusing on the direct and indirect signs that are encountered in conventional radiography and computed tomography; our personal experience is also provided. PMID- 26827735 TI - Small Bowel Perforations: What the Radiologist Needs to Know. AB - The incidence of small bowel perforation is low but can develop from a variety of causes including Crohn disease, ischemic or bacterial enteritis, diverticulitis, bowel obstruction, volvulus, intussusception, trauma, and ingested foreign bodies. In contrast to gastroduodenal perforation, the amount of extraluminal air in small bowel perforation is small or absent in most cases. This article will illustrate the main aspects of small bowel perforation, focusing on anatomical reasons of radiological findings and in the evaluation of the site of perforation using plain film, ultrasound, and multidetector computed tomography equipments. In particular, the authors highlight the anatomic key notes and the different direct and indirect imaging signs of small bowel perforation. PMID- 26827736 TI - Perforated Appendicitis: Assessment With Multidetector Computed Tomography. AB - Appendicitis is one of the most common abdominal surgical emergencies. In some cases, the correct diagnosis may be challenging, owing to different conditions that can mimic this pathology. In this context, abdominal computed tomography (CT) is the imaging modality of choice, leading to an accurate diagnosis and to a reduction in unnecessary laparotomies. The diagnosis of perforated appendix is crucial, but the detection of the perforation signs by CT may not be so simple in the early process. The aim of this article is to review the multiple detector CT signs of perforated appendicitis. PMID- 26827737 TI - Acute Perforated Diverticulitis: Assessment With Multidetector Computed Tomography. AB - Colonic diverticulitis is a common condition in the western population. Complicated diverticulitis is defined as the presence of extraluminal air or abscess, peritonitis, colon occlusion, or fistulas. Multidetector row computed tomography (MDCT) is the modality of choice for the diagnosis and the staging of diverticulitis and its complications, which enables performing an accurate differential diagnosis and addressing the patients to a correct management. MDCT is accurate in diagnosing the site of perforation in approximately 85% of cases, by the detection of direct signs (focal bowel wall discontinuity, extraluminal gas, and extraluminal enteric contrast) and indirect signs, which are represented by segmental bowel wall thickening, abnormal bowel wall enhancement, perivisceral fat stranding of fluid, and abscess. MDCT is accurate in the differentiation from complicated colon diverticulitis and colon cancer, often with a similar imaging. The computed tomography-guided classification is recommended to discriminate patients with mild diverticulitis, generally treated with antibiotics, from those with severe diverticulitis with a large abscess, which may be drained with a percutaneous approach. PMID- 26827738 TI - Role of Multidetector Computed Tomography in the Diagnosis of Colorectal Perforations. AB - Colonic perforations can be classified into perforations that occur at the site of a localized pathologic process and cecal perforations that occur secondary to distal colonic obstructions. Rectal perforations may result from foreign bodies inserted into the rectum; moreover, deep rectal biopsies, polypectomy, improper cleansing enema, or thermometer placement may also lead to rectal perforation. Correct identification of the cause and site of the perforation is crucial for appropriate management and surgical planning. Multidetector row computed tomography has a pivot role in planning the type of operative treatment, the prognosis, and in assessing those patients who have clinical symptoms of peritonitis but no radiographic signs of perforation. PMID- 26827739 TI - Gastrointestinal Tract Perforation in the Newborn and Child: Imaging Assessment. AB - Gastrointestinal tract perforation can arise from various underlying etiologies ranging from congenital causes to ingested foreign bodies in the pediatric patient population. Imaging assessment in patients with suspected gastrointestinal tract perforation plays a central role in making the diagnosis and follow-up evaluation. This article reviews the more common etiologies of gastrointestinal tract perforation in pediatric patients, their imaging manifestations, and strategies for imaging assessment to assist the radiologist in arriving at a timely and accurate diagnosis. PMID- 26827740 TI - Imaging Patients With Alimentary Tract Perforation: Literature Review. AB - Alimentary tract perforation is a frequent emergency condition. Imaging plays an important role to make an accurate diagnosis, defining the presence, the level, and the cause of the perforation, essential information to enable the most correct therapeutic choice. Plain radiography is generally performed as the first choice. In case of a clinically suspected bowel perforation, not detected on x ray imaging, the contribution of computed tomography is essential. Magnetic resonance is not yet widely used in diagnostic workup of patients with acute abdominal pain, but it can be useful in the differential diagnosis of acute abdomen in specific patients (pregnancy and pediatric patients). PMID- 26827741 TI - In situ expression of M2 macrophage subpopulation in leprosy skin lesions. AB - The clinical manifestations of the leprosy depend on host immune response and the macrophages are the primary cells involved in this process. M1 and M2 cells exhibited distinct morphology, distinct surface marker profiles, as well as different cytokine and chemokine secretion. Macrophages express receptors such as CD163, CD68, CD206, and costimulatory molecules such as CD80 and CD86, and cytokines that trigger a suppressive or inflammatory response. Thirty-three untreated patients were selected, 17 patients had the tuberculoid leprosy (TT) and 16 had the lepromatous leprosy (LL). We performed immunohistochemistry to detect IL-13, IL-10, TGF-beta, FGF-beta, CD163, CD68, arginase 1. M2 macrophages showed significant differences between the groups studied with increase in the expression of costimulatory molecules (CD68 and CD163), arginase 1 and cytokines (IL-10, IL-13, TGF-beta and FGF-b) in the LL form. Response of M2 macrophages emerge as an alternative for a better understanding of the innate immunity in the polar forms of leprosy, highlighting the role of cytokines, arginase 1 and costimulatory molecules in the repair and suppressive responses in the lepromatous form of the disease. PMID- 26827742 TI - A high throughput analysis of cytokines and chemokines expression during the course of Trypanosoma cruzi experimental oral infection. AB - Trypanosoma cruzi has high biological and biochemical diversity and variable tissue tropism. Here we aimed to verify the kinetics of cytokine and chemokine in situ secretion in animals infected with two distinct T. cruzi strains after oral inoculation. Also, we investigated parasite migration, residence and pathological damage in stomach, heart and spleen. Our results showed that host immune response against T. cruzi infection is an intricate phenomenon that depends on the parasite strain, on the infected organ and on the time point of the infection. We believe that a wide comprehension of host immune response will potentially provide basis for the development of immunotherapeutic strategies in order to clear parasitism and minimize tissue injury. In this context, we find that KC poses as a possible tool to be used. PMID- 26827744 TI - Cardiotoxicity of Anticancer Therapies. AB - Cardiovascular diseases and cancer continue to remain major causes of mortality and morbidity. However, overall cancer death rates have declined 20% from their peak in 1991. These declines reflect changing patterns in smoking, prevention, earlier diagnosis, and better treatment options in chemotherapy. It is recognized that this improved survival with better cancer therapies has put patients at risk for cardiovascular disease later in life; this may be secondary to risk factors for developing cardiovascular disease or the effect of anticancer therapies. Earlier detection, identifying patients at risk of developing cardiotoxicity, and early institution of treatment are paramount to decreasing morbidity associated with cardiotoxicity. Adverse cardiac effects have been observed and reported with a wide variety of chemotherapeutic agents. Herein we review cardiac effects of some of the common agents used in oncology. PMID- 26827745 TI - The Evolution of Coronary Revascularization Appropriateness Use Criteria: From Mandatory to Forgotten. AB - The appropriateness use criteria (AUC) for coronary revascularization have been formulated through the joint efforts of several professional societies. The goals of AUC were to aid in physician decision making and to objectively define the need and context for revascularization. These criteria, developed using a standardized approach, were widely promoted and adopted in many practices. Rigorous use in daily practice and public reporting of adherence to these criteria has exposed some of their deficiencies. Revisions to the original version were made to accommodate public and physician sentiments. Not surprisingly, the recent percutaneous coronary intervention performance measures developed by the same professional societies that have proposed AUC, have suggested that AUC should be used for internal quality improvement only at this time. Therefore, the present role and future application of AUC to cardiology practice is uncertain. The goals of this review are to describe methodology and development of the coronary revascularization AUC, to focus on the strengths and limitations of AUC, and to identify challenges related to application of these criteria in daily practice. PMID- 26827743 TI - BbrzSP-32, the first serine protease isolated from Bothrops brazili venom: Purification and characterization. AB - Snake venom toxins are related not only in detention, death and the promotion of initial digestion of prey but also due to their different biochemical, structural and pharmacological effects they can result in new drugs. Among these toxins snake venom serine proteases (SVSPs) should be highlighted because they are responsible for inducing changes in physiological functions such as blood coagulation, fibrinolysis, and platelet aggregation. This article presents the first serine protease (SP) isolated from Bothrops brazili: BbrzSP-32. The new SP showed 36 kDa of relative molecular mass and its absolute mass was confirmed by mass spectrometry as 32,520 Da. It presents 79.48% identity when compared to other SVSPs and was able to degrade the alpha-chain of fibrinogen, in in vitro models, because of this it is considered a SVTLE-A. It showed dose-dependent activity in the process of degradation of fibrin networks demonstrating greater specificity for this activity when compared to its thrombolytic action. BbrzSP-32 demonstrated proteolytic activity on gelatin and chromogenic substrates for serine proteases and thrombin-like enzymes (S-2288 and S-2238 respectively), besides having coagulant activity on human plasma. After pre-incubation with PMSF and benzamidine the coagulant and proteolytic activities on the S-2288 and S-2238 substrates were reduced. BbrzSP-32 shows stability against pH and temperature variations, demonstrating optimum activity between 30 and 40 degrees C and in the pH range 7.5 to 8.5. A new SP with potential biotechnological application was isolated. PMID- 26827746 TI - Takotsubo Cardiomyopathy: Clinical Characteristics and Outcomes. AB - Takotsubo cardiomyopathy (TC) is a reversible characteristic of left ventricular (LV) ballooning on cardiac imaging without significant coronary artery disease that is precipitated by stress. We performed a retrospective analysis of consecutive patient records to analyze outcomes of patients with TC. Of 100 patients with TC (90% women, mean age 67.7 y, SD = 15.96), 44 patients presented to the emergency room with chest pain, biomarker elevation, and electrocardiographic changes (ST segment elevation in 47%; primary TC) and 56 patients subsequently developed TC after an alternative initial diagnosis (ST segment elevation 27%; secondary TC; P = 0.04). Inciting events differed in those with primary versus secondary TC, with 48% of primary TC patients describing emotional stress; most secondary TC (75%) manifested after a surgical procedure or infection. Average length of hospital stay for primary TC was 6.68 days (SD = 5.32, range 1-28 d) and 18.22 (SD = 20.76, range 3-129 d) for secondary TC (P < .0001). Time to resolution of LV function was equal in both groups. With regard to mortality, eight of nine deaths occurred in secondary TC patients, and all nine deaths were attributable to comorbid medical conditions. Primary TC is frequently related to emotional stress, and carries a benign prognosis. Secondary TC is associated with an acute medical condition and results in a higher death rate. PMID- 26827748 TI - Giant Thoracic Aneurysm Following Valve Replacement for Bicuspid Aortic Valve. AB - Bicuspid aortic valve is a common congenital anomaly associated with aortopathy, which can cause aortic root dilatation, necessitating regular screening if the aortic root is > 4.0 cm. Despite the low absolute incidence of aortic complications associated with bicuspid aortic valve in the general population, the consequences of such complications for an individual patient can be devastating. Herein we propose a balanced algorithm that incorporates recommendations from the three major guidelines for follow-up imaging of the aortic root and ascending thoracic aorta in patients with a bicuspid aortic valve, maintaining the current recommendations with regard to surgical thresholds. PMID- 26827747 TI - News From the California Chapter of The American College of Cardiology. PMID- 26827749 TI - Myocardial Infarction Related to Trauma. AB - Myocardial infarction (MI) secondary to acute coronary occlusion related to trauma is rare. A previously healthy man developed acute MI shortly after a motor vehicle accident. This case illustrates the feasibility of primary percutaneous coronary intervention for acute MI due to complete coronary artery occlusion related to trauma, including the use of manual thrombectomy, stents, and dual antiplatelet therapy. This approach requires the intervention of a multidisciplinary team in a Level 1 trauma center that can rapidly evaluate the patient and rule out other life-threatening injuries that could preclude antiplatelet therapy. PMID- 26827750 TI - Pseudomonas populi sp. nov., an endophytic bacterium isolated from Populus euphratica. AB - A Gram-stain negative, aerobic, non-motile, short-rod-shaped bacterium, designated KBL-4-9T, was isolated from the storage liquid in the stems of Populus euphratica trees in Xinjiang, PR China. Strain KBL-4-9T grew at 4-45 degrees C (optimum 37 degrees C), 1-3 % (w/v) NaCl (optimum 1 %, w/v) and pH 5.5-9.5 (optimum pH 7.5). Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain KBL-4-9T belonged to the genus Pseudomonas and showed the highest 16S rRNA gene sequence similarity of 97.36 % to Pseudomonas pelagia CL AP6T, followed by Pseudomonas xinjiangensis S3-3T (97.16 %), Pseudomonas sabulinigri J64T (97.15 %) and Pseudomonas xiamenensis C10-2T (96.47 %). Analysis of strain KBL-4-9T based on the three housekeeping genes, rpoB, rpoD and gyrB, further confirmed the phylogenetic assignment of the isolates. The DNA G+C content was 61.6 mol% (sd = 2.19). DNA-DNA hybridization with P. pelagia CL-AP6T, P. xinjiangensis S3-3T and P. sabulinigri J64T revealed 49.3 % (sd = 3.04), 41.2 % and 52.5 % (sd = 4.45) relatedness, respectively. The major cellular fatty acids of strain KBL-4-9T were C16 : 0, C12 : 0, summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c) and C17 : 0 cyclo. The major isoprenoid quinone was Q-9. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and phosphatidylcholine. On the basis of phenotypic, chemotaxonomic and phylogenetic properties, strain KBL-4-9T is considered to represents a novel species of the genus Pseudomonas, for which the name Pseudomonas populi sp. nov. is proposed. The type strain is KBL-4-9T ( = JCM 19138T = CCTCC AB 2013069T = NRRL B-59988T). PMID- 26827751 TI - Design and use of silica-containing redox nanoparticles, siRNPs, for high performance peritoneal dialysis. AB - The prevention of encapsulating peritoneal sclerosis (EPS) and the enhancement of dialysis efficiency are two important strategies that can improve the quality of life of patients undergoing peritoneal dialysis. We have thus far developed bionanoparticles that effectively scavenge reactive oxygen species (redox nanoparticles; RNPs). The objective of this study was to apply RNPs as a component of dialysate to reduce oxidative stress. Porous silica nanoparticles were combined with RNPs to enhance the effective adsorption capacity of low molecular weight (LMW) compounds. The silica-containing RNPs (siRNPs) were confirmed to statistically decrease the level of creatinine and blood urea nitrogen in vivo. EPS model rats that underwent an intraperitoneal injection of chlorhexidine gluconate exhibited dysfunction of the peritoneal membrane. siRNP administration did not result in dysfunction of the peritoneal membrane. An LMW nitroxide compound, TEMPOL, also showed a weak peritoneal protective effect, although its efficiency was limited. No blood uptake of siRNPs was observed when they were administered into the peritoneal cavity. However, LMW-TEMPOL diffused into the blood stream, which might have decreased its effective concentration in the peritoneal cavity and led to adverse effects across the entire body. Considering these results, siRNPs are expected to be a new multi-functional nanomaterial for high performance peritoneal dialysis. PMID- 26827752 TI - Pharmacokinetics and transgene expression of implanted polyethylenimine-based pDNA complexes. AB - Locally delivered plasmid DNA (pDNA) is currently pursued as gene-based therapy for regenerative medicine, but important information on in situ pDNA pharmacokinetics and transgene expression is lacking in animal models. To investigate pDNA pharmacokinetics in implants, low molecular weight (2 kDa) polyethylenimine (PEI) and linoleic acid substituted 2 kDa PEI (PEI-LA) were used for pDNA delivery in gelatin sponges. An efficient pDNA extraction method combined with quantitative PCR (qPCR) was found to give equivalent quantitation of naked and polymer-bound pDNA, making it suitable to assess pDNA polyplexes in implants. Naked pDNA implanted in a rat subcutaneous model was >98% lost after 24 hours whereas PEI and PEI-LA delivered pDNA remained intact in implants for 2 and 4 weeks, respectively. Using a plasmid expressing DsRed as a reporter gene, mRNA and protein expression was observed only for PEI-LA despite the extended retention and cellular uptake of PEI complexes. The in vivo data were in agreement with in vitro results showing that only PEI-LA was an effective transfection agent even though both PEI and PEI-LA complexes were internalized by the cells. Dose dependence was observed for mRNA expression, with a 20 MUg dose giving faster onset and higher expression levels compared to a 5 MUg pDNA dose. The mRNA expression after PEI-LA mediated delivery was sustained for at least 4 weeks and a significant correlation between pDNA retention in sponges and mRNA expression was observed. In addition to establishing a promising gene carrier for gene delivery, these studies provided important information about the retention and transgene expression by implanted non-viral carriers. PMID- 26827753 TI - Alkynyl bridged cyclometalated Ir2M2 clusters: impact of the heterometal in the photo- and electro-luminescence properties. AB - We report two unprecedent alkynyl bridging cyclometalated clusters [Ir2M2(ppy)4(MU-C[triple bond, length as m-dash]CC6H4-OMe3)4] where M is Ag (2) and Cu (3), which display distinctive luminescence properties. While 2 features a green phosphorescence/electroluminescence nature located at the ppy ligands ((3)LC), 3 shows an orange emission confined to the metals and alkynyl groups having a mixed (3)L'C/(3)L'MCT/(3)MMCT (L' = alkynyl) nature. PMID- 26827754 TI - A collagen-based corneal stroma substitute with micro-designed architecture. AB - A 3D corneal stroma substitute with micro-level patterns was constructed from a stack of 4 micro patterned collagen or collagen-elastin like recombinamer (Col:ELR) blend layers. The transparency of all of the films was quite high with the uncrosslinked (UXL) films and dehydrothermally treated (150 degrees C, 24 h) Col:ELR films yielding the best results. Human corneal keratocytes (HK) could be attached and proliferated equally well on the single films of Col and Col:ELR. However, for the multilayer constructs the proliferation was higher on Col than on Col:ELR. The cells were found to align along the patterns (microchannels with a 39 MUm groove depth, 8 MUm groove width, 3.3 MUm ridge width, and 54.7 degrees inclination angle) of the films, while no significant alignment was observed on the unpatterned films. The transparency of the seeded Col:ELR films was superior to the Col films over a 30 day incubation period and was quite close to that of a native human cornea. It was concluded that the Col and Col:ELR films and their 3D constructs have significant potential for use as corneal stroma substitutes. PMID- 26827755 TI - Sulfobetaine-terminated PEG improves the qualities of an immunosensing surface. AB - Poly(ethylene glycol) (PEG) possessing a sulfobetaine (SB) moiety at one end and a pentaethylenehexamine (N6) at the other end (SB-PEG-N6) was newly synthesized as a blocking agent for immunosensing surfaces. The N6 moiety strongly coordinates on gold surfaces, facilitating the tethering of the PEG chain to the sensor chip surface, and leaves the SB moiety free. Non-specific adsorption of bovine serum albumin (BSA) was analyzed on the SB-PEG-N6 tethered surface and compared with the methoxy-PEG-N6 (M-PEG-N6) tethered surface using a surface plasmon resonance (SPR) sensor. Non-specific BSA adsorption decreased with decreasing PEG chain length on the SB-PEG tethered chain surface. Non-specific adsorption of BSA decreased as ionic strength increased on SB-PEG-N6 surfaces; this phenomenon was completely opposite to that observed with an M-PEG-N6 tethered chain surface. The results show that SB moieties located close to the gold surface perform well with regard to protein rejection. Actually, low molecular weight alkane thiol SB (SB-SH) showed minimum BSA adsorption. To evaluate protein recognition efficacy on a PEGylated surface, an antibody (IgG) immobilized surface was then constructed on a gold sensor chip using SB-PEG-N6 as the blocking agent. The specific protein recognition efficacy of SB-PEG-N6/IgG co immobilized surfaces was higher than that obtained using SB-SH/IgG co-immobilized surfaces. We conclude that SB-terminated PEG exhibits the optimal qualities of a blocking agent, as it possesses both high suppression efficacy of nonspecific protein adsorption and specific protein recognition ability. PMID- 26827757 TI - Rheology of kappa/iota-hybrid carrageenan from Mastocarpus stellatus: Critical parameters for the gel formation. AB - The sol-gel diagrams of kappa/iota-hybrid carrageenan (KI) extracted from Mastocarpus stellatus powders with two different average particle sizes of the seaweed powders (117.0 MUm and 77.5 MUm) prior to the biopolymer extraction, are reported for the first time, together with rheological properties of obtained KI gels. Extraction yields for KI isolated from algae and average molecular weight of KI, determined by gel permeation chromatography, decreased with increasing the particle size of the powder. Rheological results indicated that tested samples exhibited stable and weak gel properties, except those prepared at 1.5% KI in 1.0 mol/L NaCl where stronger gels were found. Aqueous KI extracts with larger molecular weight led to stronger gels and also formed gels at lower biopolymer concentration in NaCl above 0.15 mol/L. All gels reached stability after 20 min of maturation. The data sets showed a strong temperature dependency. Gel setting temperatures significantly depended on the KI and NaCl content, whereas gel melting temperatures (68.0 +/- 0.7 degrees C) were independent of both salt concentrations. PMID- 26827756 TI - Modeling of polysaccharide extraction from Gossypium arboreum L. seed using central composite rotatable design. AB - The present study investigates the effect of independent variables such as extraction temperature (35-55 degrees C), time (1-5h) and solid-liquid ratio (1:5-1:25 g/ml) over the extraction yield of polysaccharide from Gossypium arboreum L. seeds was investigated and optimized. Aqueous extraction method was opted for the extraction of polysaccharide. Central composite response surface design was utilized for developing the experimental design. A second order polynomial mathematical model was developed from the obtained results. From the results, Significance of process variables over the extraction process can be clearly depicted. At the extraction temperature of 45 degrees C, extraction time of 3h and solid-liquid ratio of 1:15 g/ml maximum yield of polysaccharide (8.67%) from Gossypium arboreum L. seed was obtained. Characteristics of the extracted polysaccharide are analyzed through physico-chemical property analysis and Fourier Transform Infrared Spectroscopy (FTIR). PMID- 26827758 TI - Comparative characterization of three bacterial exo-type alginate lyases. AB - Alginate, a major acidic polysaccharide in brown macroalgae, has attracted attention as a carbon source for production of ethanol and other chemical compounds. Alginate is monomerized by exo-type alginate lyase into an unsaturated uronate; thus, this enzyme is critical for the saccharification and utilization of alginate. Although several exo-type alginate lyases have been characterized independently, their activities were not assayed under the same conditions or using the same unit definition, making it difficult to compare enzymatic properties or to select the most suitable enzyme for saccharification of alginate. In this study, we characterized the three bacterial exo-type alginate lyases under the same conditions: A1-IV of Sphingomonas sp. strain A1, Atu3025 of Agrobacterium tumefaciens, and Alg17c of Saccharophagus degradans. A1-IV had the highest specific activity as well as the highest productivity of uronate, whereas Alg17c had the lowest activity and productivity. Only dialyzed Atu3025 and Alg17c were tolerant to freezing. Alg17c exhibited a remarkable halotolerance, which may be advantageous for monomerization of alginate from marine brown algae. Thus, each enzyme exhibited particular desirable and undesirable properties. Our results should facilitate further utilization of the promising polysaccharide alginate. PMID- 26827759 TI - Swelling behavior of poly(N-cyclohexylacrylamide-co-acrylamide/AMPSNa) gold nanocomposite hydrogels. AB - In this study, poly(N-cyclohexylacrylamide-co-acrylamide/sodium 2-acrylamido-2 methyl propanesulfonate) gold nanocomposite hydrogels were synthesized by free radical copolymerization in methanol/water at 60 degrees C. The gold nanocomposites hydrogels were prepared via in situ polymerization using gold nanoparticle. The weight percentage of N-cyclohexylacrylamide (NCA) and acrylamide (AM) monomers was fixed 50:50 and the weight of sodium 2-acrylamido-2 methylpropanesulfonate (AMPSNa) was varied from 0.1 to 0.5 g. The swelling behavior of gold nanocomposite hydrogels was studied by gravimetric method and it was found that swelling increases as the amount of sodium 2-acrylamido-2 methylpropanesulfonate increases. The surface morphology study indicates the formation of spherical shaped gold nanoparticle in the polymer matrix. PMID- 26827761 TI - Intrathecal Minocycline Suppresses Itch-Related Behavior and Improves Dermatitis in a Mouse Model of Atopic Dermatitis. PMID- 26827762 TI - Development and Validation of the Vitiligo Extent Score (VES): an International Collaborative Initiative. AB - The clinical assessment of vitiligo involves an estimation of the affected body surface area. The most commonly used method is the "palm of hand 1% rule" as integrated in the Vitiligo Area Scoring Index. However, this method can be challenging and time consuming. In this study, we introduce a global Vitiligo Extent Score (VES). In the first part of the study, this measurement instrument was developed and subsequently optimized during a pilot scoring session. In a subsequent stage, the inter- and intrarater reliability of the instrument were tested. Live scoring showed an excellent interrater reliability for the VES (intraclass correlation VES: 0.924 vs. Vitiligo Area Scoring Index: 0.846). Subsequent scoring on pictures was comparable with the live evaluation and demonstrated an excellent intrarater reliability. A high intraclass correlation for the VES (intraclass correlation VES: 0.923 vs. Vitiligo Area Scoring Index: 0.757) was also found in an additional subgroup of patients with extensive vitiligo. Moreover, user-friendliness and timing were scored very favorably. In conclusion, this measurement instrument allows us to monitor accurately and easily the affected body surface area in a standardized way. Moreover, our results provide evidence that the VES can be proposed as a promising tool to measure the vitiligo extent in clinical trials and in daily practice. PMID- 26827760 TI - Phenotypic and Histopathological Tumor Characteristics According to CDKN2A Mutation Status among Affected Members of Melanoma Families. PMID- 26827763 TI - Collagen XVII Shedding Suppresses Re-Epithelialization by Directing Keratinocyte Migration and Dampening mTOR Signaling. AB - Transmembrane collagen XVII is traditionally viewed as an important hemidesmosomal attachment component that promotes stable dermal-epidermal adhesion in the skin. However, its expression is highly elevated at the leading edges of cutaneous wounds or invasive carcinomas, suggesting alternative functions in cell migration. The collagenous ectodomain of collagen XVII is constitutively shed from the cell surface by a disintegrin and metalloproteinases, and this shedding is strongly induced during wound healing. Recently, we investigated the physiological relevance of collagen XVII shedding by generating knock-in mice, which exclusively express a functional non-sheddable collagen XVII mutant. Prevention of ectodomain shedding in these mice caused no spontaneous phenotype in resting skin, but accelerated re-epithelialization on skin wounding. Here, we investigated the mechanistic function of shedding during wound healing. Using the non-shedding collagen XVII mice as a model, we uncovered ectodomain shedding as a highly dynamic modulator of in vivo proliferation and motility of activated keratinocytes through tight coordination of alpha6beta4 integrin-laminin-332 interactions and dampening of mechanistic target of rapamycin signaling at the wound edges. Thus, our studies identify ectodomain shedding of collagen XVII as an interactive platform that translates shedding into a signal for directed cell growth and motility during skin regeneration. PMID- 26827765 TI - Epitope-Dependent Pathogenicity of Antibodies Targeting a Major Bullous Pemphigoid Autoantigen Collagen XVII/BP180. AB - In bullous pemphigoid, the common autoimmune blistering disorder, IgG autoantibodies target various epitopes on hemidesmosomal transmembrane collagen XVII (COL17)/BP180. Antibodies (Abs) targeting the extracellular noncollagenous 16th A domain of COL17 may be pathogenic; however, the pathogenic roles of Abs targeting non-noncollagenous 16th A regions are poorly understood. In this study using a pathogenic and a nonpathogenic monoclonal antibody (mAb) targeting the noncollagenous 16th A domain (mAb TS39-3) and the C-terminus domain (mAb C17-C1), respectively, we show that endocytosis of immune complexes after binding of Abs to cell surface COL17 is a key phenomenon that induces skin fragility. Passive transfer of IgG1 mouse mAb TS39-3 but not mAb C17-C1 induces dermal-epidermal separation in neonatal human COL17-expressing transgenic mice. Interestingly, mAb C17-C1 strongly binds with the dermal-epidermal junction of the recipient mice skin, suggesting that binding of Abs with COL17 is insufficient to induce skin fragility. In cultured normal human epidermal keratinocytes treated with these mAbs, mAb TS39-3 but not mAb C17-C1 internalizes immune complexes after binding with cell surface COL17 via macropinocytosis, resulting in reduced COL17 expression. This study shows that pathogenicity of Abs targeting COL17 is epitope dependent, which is associated with macropinocytosis-mediated endocytosis of immune complexes and finally results in the depletion of COL17 expression in basal keratinocytes. PMID- 26827764 TI - ABCB5-Targeted Chemoresistance Reversal Inhibits Merkel Cell Carcinoma Growth. AB - Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer with profound but poorly understood resistance to chemotherapy, which poses a significant barrier to clinical MCC treatment. Here we show that ATP-binding cassette member B5 (ABCB5) confers resistance to standard-of-care MCC chemotherapeutic agents and provide proof-of-principle that ABCB5 blockade can inhibit human MCC tumor growth through sensitization to drug-induced cell cytotoxicity. ABCB5 expression was detected in both established MCC lines and clinical MCC specimens at levels significantly higher than those in normal skin. Carboplatin- and etoposide-resistant MCC cell lines exhibited increased expression of ABCB5, along with enhanced ABCB1 and ABCC3 transcript expression. ABCB5-expressing MCC cells in heterogeneous cancers preferentially survived treatment with carboplatin and etoposide in vitro and in human MCC xenograft bearing mice in vivo. Moreover, patients with MCC also exhibited enhanced ABCB5 positivity after carboplatin- and etoposide-based chemotherapy, pointing to clinical significance of this chemoresistance mechanism. Importantly, ABCB5 blockade reversed MCC drug resistance and impaired tumor growth in xenotransplantation models in vivo. Our results establish ABCB5 as a chemoresistance mechanism in MCC and suggest utility of this molecular target for improved MCC therapy. PMID- 26827766 TI - Single Amino Acid Deletion in Kindlin-1 Results in Partial Protein Degradation Which Can Be Rescued by Chaperone Treatment. AB - Kindler syndrome, a distinct type of epidermolysis bullosa, is a rare disorder caused by mutations in FERMT1, encoding kindlin-1. Most FERMT1 mutations lead to premature termination codons and absence of kindlin-1. Here we investigated the molecular and cellular consequences of a naturally occurring FERMT1 mutation, c.299_301del resulting in a single amino acid deletion, p.R100del. The mutation led to a 50% reduction of FERMT1 mRNA and 90% reduction of kindlin-1 protein in keratinocytes derived from the patient, as compared with control cells. The misfolded p.R100del kindlin-1 mutant was lysosomally degraded and launched a homeostatic unfolded protein response. Sodium-phenylbutyrate significantly increased kindlin-1 mRNA and protein levels and the area of mutant cells, acting as a chemical chaperone and probably also as a histone deacetylase inhibitor. In a recombinant system, low levels of wild-type or p.R100del mutant kindlin-1 were sufficient to improve the cellular phenotype in respect of spreading and proliferation as compared with kindlin-1 negative keratinocytes. The study of this hypomorphic mutation provides evidence that low amounts of kindlin-1 are sufficient to improve the epidermal architecture and Kindler syndrome cellular phenotype and proposes a personalized chaperone therapy for the patient. PMID- 26827768 TI - Kinetic modeling and docking study of immobilized lipase catalyzed synthesis of furfuryl acetate. AB - The present work deals with the kinetic modeling and docking study for the furfuryl acetate synthesis using immobilized Burkholderia cepacia (BCL) lipase. Initially various lipases were immobilized on hydroxypropyl methyl cellulose (HPMC) and poly vinyl alcohol (PVA) base hybrid polymer matrix. After screening of various immobilized biocatalysts, HPMC:PVA:BCL was found to be a robust biocatalyst. Various reaction conditions were optimized using response surface methodology (RSM) based on a four-factor-three-level Box-Behnken design. The optimal conditions were obtained at molar ratio of 1:2 of furfuryl alcohol to acyl donor, temperature 50 degrees C with catalyst loading of 30mg in 3mL of non aqueous media toluene. Under these conditions 99.98% yield was obtained in 3h. The Arrhenius plot showed that the activation energy for furfuryl acetate synthesis was 10.68kcal/mol. The kinetics of reaction was studied close to optimized conditions which obey order bi-bi model. Molecular docking study was carried out to understand the active site of BCL which is responsible for the reaction. It was observed that the reaction proceeds via acylation of the active serine of BCL and demonstrating strong hydrogen bond between the substrate and histidine site. The catalyst recyclability study was carried up to five cycles. PMID- 26827767 TI - Resveratrol augments therapeutic efficiency of mouse bone marrow mesenchymal stem cell-based therapy in experimental autoimmune encephalomyelitis. AB - Experimental autoimmune encephalitis (EAE) is an inflammatory demyelinating disease, which served as a useful model providing considerable insights into the pathogenesis of multiple sclerosis (MS). Mouse bone marrow mesenchymal stem cells (mBM-MSC) were shown to have neuroprotection capabilities in EAE. Resveratrol is a small polyphenolic compound and possess therapeutic activity in various immune mediated diseases. The sensitivity of mBM-MSCs to resveratrol was determined by an established cell-viability assay. Resveratrol-treated mBM-MSCs were also characterized with flow cytometry using MSC-specific surface markers and analyzed for their multiple differentiation capacities. EAE was induced in C57BL/6 mice by immunization with MOG35-55. Interferon gamma (IFN-gamma)/tumor necrosis factor alpha (TNF-alpha) and interleukin-4 (IL-4)/interleukin-10 (IL-10), the hallmark cytokines that direct T helper type 1 (Th1) and Th2 development, were detected with enzyme-linked immunosorbent assay (ELISA). In vivo efficacy experiments showed that mBM-MSCs or resveratrol alone led to a significant reduction in clinical scores, and combined treatment resulted in even more prominent reduction. The combined treatment with mBM-MSCs and resveratrol enhanced the immunomodulatory effects, showing suppressed proinflammatory cytokines (IFN gamma, TNF-alpha) and increased anti-inflammatory cytokines (IL-4, IL-10). The combination of mBM-MSCs and resveratrol provides a novel potential experimental protocol for alleviating EAE symptoms. PMID- 26827769 TI - Lysine epsilon-aminotransferases: kinetic constants, substrate specificities, and the variation in active site residues. AB - L-Lysine epsilon-aminotransferase (lysAT) is an important enzyme in tailoring the terminal amino group of L-lysine or L-ornithine and can be directed to the synthesis of various value-added chemicals such as adipic acid. Three lysATs, lysAT from Saccharopolyspora erythraea NRRL 2338 (lysAT_Sery), lysAT from Nocardia farcinica IFM 10152, and lysAT from Rhodococcus jostii RHA1, were cloned, and their kinetic values and substrate specificities were investigated. In the reaction using 5mM L-lysine and 10mM alpha-ketoglutarate, lysAT_Sery from S. erythraea NRRL 2338 showed 72% higher specific activity than lysAT from Nocardia farcinica IFM 10152 and 42% higher specific activity than lysAT from R. jostii RHA1. More interesting result was that lysAT Sery, exhibiting the highest activity among three lysATs, did not show any activity to L-ornithine. The alignment of 146 lysAT sequences from RefSeq database was searched by the EC number of lysAT to compare the active site residues among the lysAT sequences. The sequence alignment showed that only two residues, corresponding to Ala129 and Asn328 of lysAT from Mycobacterium tuberculosis H37Rv (lysAT_Mtub), showed variations among the active site residues. All the active site residues except those two residues were completely conserved throughout 145 lysAT sequences. lysAT from S. erythraea NRRL 2338 has A129T and N328S variations (residue numbers are those of the crystal structure of lysAT_Mtub). The structural analysis by the homology model indicate that Thr126 by A129T variation in lysAT_Sery is appeared to interact more tightly with the phosphate group of PLP than alanine (the distance between Thr126 and the phosphate group of PLP was 2.92A). In addition, Ser328 is located at the substrate recognition site of active site and, therefore, N328S variation may be connected to the substrate specificity of lysAT. PMID- 26827770 TI - A biosensor based on gold nanoparticles, dihexadecylphosphate, and tyrosinase for the determination of catechol in natural water. AB - In this work, a biosensor using a glassy carbon electrode modified with gold nanoparticles (AuNPs) and tyrosinase (Tyr) within a dihexadecylphosphate film is proposed. Cystamine and glutaraldehyde crosslinking agents were used as a support for Tyr immobilization. The proposed biosensor was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and cyclic voltammetry in the presence of catechol. The determination of catechol was carried out by amperometry and presented a linear concentration range from 2.5*10(-6) to 9.5*10(-5)molL(-1) with a detection limit of 1.7*10(-7)molL(-1). The developed biosensor showed good repeatability and stability. Moreover, this novel amperometric method was successfully applied in the determination of catechol in natural water samples. The results were in agreement with a 95% confidence level for those obtained using the official spectrophotometric method. PMID- 26827771 TI - A novel metagenome-derived gene cluster from termite hindgut: Encoding phosphotransferase system components and high glucose tolerant glucosidase. AB - Functional screening of a metagenomic library of termite hindgut identified an overlapping gene cluster encoding the phosphotransferase system (PTS) components, which consisted of a glucoside specific PTS enzyme II gene (glu1923) and a glycoside hydrolase gene (glu1392). Hydrolytic experiments revealed that the combined effect of Glu1923 and Glu1392 was responsible for the utilization of glucosidic substrates in recombinant Escherichia coli (E. coli) strains. Yeast two hybrid analysis suggested that there was an interaction between Glu1923 and Glu1392, and the domain EIIA of Glu1923 played an important role for the interaction. In addition, the hydrolase Glu1392 displayed hydrolysis ability toward cellobiose and maltose, and had a very high tolerance to glucose with a Ki value of 2.25M. These properties make Glu1392 an interesting candidate in biotechnology applications after further study. PMID- 26827772 TI - First Novozym 435 lipase-catalyzed Morita-Baylis-Hillman reaction in the presence of amides. AB - The first Novozym 435 lipase-catalyzed Morita-Baylis-Hillman (MBH) reaction with amides as co-catalyst was realized. Results showed that neither Novozym 435 nor amide can independently catalyze the reaction. This co-catalytic system that used a catalytic amount of Novozym 435 with a corresponding amount of amide was established and optimized. The MBH reaction strongly depended on the structure of aldehyde substrate, amide co-catalyst, and reaction additives. The optimized reaction yield (43.4%) was achieved in the Novozym 435-catalyzed MBH reaction of 2, 4-dinitrobenzaldehyde and cyclohexenone with isonicotinamide as co-catalyst and beta-cyclodextrin as additive only in 2 days. Although enantioselectivity of Novozym 435 was not found, the results were still significant because an MBH reaction using lipase as biocatalyst was realized for the first time. PMID- 26827773 TI - Metal-dependent thermal stability of recombinant endo-mannanase (ManB-1601) belonging to family GH 26 from Bacillus sp. CFR1601. AB - A GH 26 endo-mannanase from Bacillus sp. CFR1601 was purified to homogeneity (Mw ~39kDa, specific activity 10,461.5+/-100IU/mg). Endo-mannanase gene (manb-1601, 1083bp, accession No. KM404299) was expressed in Escherichia coli BL21 (DE3) and showed typical fingerprints of alpha/beta proteins in the far-UV CD. A high degree of conservation among amino acid residues involved in metal chelation (His 1, 23 and Glu-336) and internal repeats (122-152 and 181-212) was observed in endo-mannanases reported from various Bacillus sp. Thermal inactivation kinetics suggested that metal ions are quintessential for stabilization of ManB-1601 structure as holoenzyme (Ea 87.4kcal/mol, DeltaH 86.7kcal/mol, DeltaS 186.6cal/k/mol) displayed better values of thermodynamic parameters compared to metal-depleted ManB-1601 (Ea 47kcal/mol, DeltaH 45.7kcal/mol, DeltaS 64.7cal/k/mol). EDTA treatment of ManB-1601 not only lead to transitions in both secondary and tertiary structure but also promulgated the population of conformational state that unfolds at lower temperature. ManB-1601 followed a three-state process for thermal inactivation wherein loss of tertiary structure preceded the concurrent loss of secondary structure and activity. PMID- 26827774 TI - Development of high-affinity single chain Fv against foot-and-mouth disease virus. AB - Foot-and-mouth disease (FMD) is caused by the FMD virus (FMDV) and results in severe economic losses in livestock farming. For rapid FMD diagnostic and therapeutic purposes, an effective antibody against FMDV is needed. Here, we developed a high-affinity antibody against FMDV by FACS-based high throughput screening of a random library. With the FITC-conjugated VP1 epitope of FMDV and high-speed FACS sorting, we screened the synthetic antibody (scFv) library in which antibody variants are displayed in the periplasm of Escherichia coli. After three rounds of sorting, we isolated one antibody fragment (#138-scFv) against the VP1 epitope of FMDV. Next, to improve its affinity, a mutation library of #138-scFV was constructed by error-prone PCR and screened by FACS. After three rounds of sorting, we isolated one antibody (AM-32 scFv), which has a higher binding affinity (KD=42.7nM) than that of the original #138-scFv. We also confirmed that it specifically binds to whole inactivated FMDV. PMID- 26827775 TI - Preparation of a biocatalyst via physical adsorption of lipase from Thermomyces lanuginosus on hydrophobic support to catalyze biolubricant synthesis by esterification reaction in a solvent-free system. AB - Lipase from Thermomyces lanuginosus (TLL) was immobilized on mesoporous hydrophobic poly-methacrylate (PMA) particles via physical adsorption (interfacial activation of the enzyme on the support). The influence of initial protein loading (5-200mg/g of support) on the catalytic properties of the biocatalysts was determined in the hydrolysis of olive oil emulsion and synthesis of isoamyl oleate (biolubricant) by esterification reaction. Maximum adsorbed protein loading and hydrolytic activity were respectively ~100mg/g and ~650 IU/g using protein loading of 150mg/g of support. The adsorption process followed the Langmuir isotherm model (R(2)=0.9743). Maximum ester conversion around 85% was reached after 30min of reaction under continuous agitation (200rpm) using 2500mM of each reactant in a solvent-free system, 45 degrees C, 20%m/v of the biocatalyst prepared using 100mg of protein/g of support. Apparent thermodynamic parameters of the esterification reaction were also determined. Under optimal experimental conditions, reusability tests of the biocatalyst (TLL-PMA) after thirty successive cycles of reaction were performed. TLL-PMA fully retained its initial activity up to twenty two cycles of reaction, followed by a slight decrease around 8.6%. The nature of the product (isoamyl oleate) was confirmed by attenuated total reflection Fourier transform infrared (ATR-FTIR), proton ((1)H NMR) and carbon ((13)C NMR) nuclear magnetic resonance spectroscopy analyses. PMID- 26827776 TI - Dendrimer-like nanoparticles based beta-galactosidase assembly for enhancing its selectivity toward transgalactosylation. AB - Functional nanomaterials have been pursued to assemble nanobiocatalysts since they can provide unique hierarchical nanostructures and localized nanoenvironments for enhancing enzyme specificity, stability and selectivity. Functionalized dendrimer-like hierarchically porous silica nanoparticles (HPSNs) was fabricated for assembling beta-galactosidase nanobiocatalysts for bioconversion of lactose to galacto-oligosaccharides (GOS). The nanocarrier was functionalized with amino (NH2) and carboxyl (COOH) groups to facilitate enzyme binding, benchmarking with non-functionalized HPSNs. Successful conjugation of the functional groups was confirmed by FTIR, TGA and zeta potential analysis. HPSNs-NH2 showed 1.8-fold and 1.1-fold higher beta-galactosidase adsorption than HPSNs-COOH and HPSNs carriers, respectively, with the highest enzyme adsorption capacity of 328mg/g nanocarrier at an initial enzyme concentration of 8mg/ml. The HPSNs-NH2 and beta-galactosidase assembly (HPSNs-NH2-Gal) demonstrated to maintain the highest activity at all tested enzyme concentrations and exhibited activity up to 10 continuous cycles. Importantly, HPSNs-NH2-Gal was simply recycled through centrifugation, overcoming the challenging problems of separating the nanocarrier from the reaction medium. HPSNs-NH2-Gal had distinguished catalytic reaction profiles by favoring transgalactosylation, enhancing GOS production of up to 122g/l in comparison with 56g/l by free beta galactosidase. Furthermore, it generated up to 46g/l GOS at a lower initial lactose concentration while the free counterpart had negligible GOS production as hydrolysis was overwhelmingly dominant in the reaction system. Our research findings show the amino-functionalized HPSNs can selectively promote the enzyme activity of beta-galactosidase for transgalactosylation, which is beneficial for GOS production. PMID- 26827777 TI - Rational design of xylose dehydrogenase for improved thermostability and its application in development of efficient enzymatic biofuel cell. AB - In this paper, the construction of 3D model structure of xylose dehydrogenase (XDH) by using homology modeling to guide the rational design of the enzyme for improving thermostability was reported. Three XDH mutants of NA-1 (+249L), NA-2 (G149P) and NA-3 (+249L/G149P) were designed and displayed on the surface of bacteria. Among them, bacteria displaying NA-1 (NA-1-bacteria) exhibited superior thermostability without compromising its activity and substrate specificity in comparison with its wild-type counterpart. NA-1-bacteria retained its original activity after incubation at room temperature for one-month with the half-life of 9.8 days at 40 degrees C. Finally, the NA-1-bacteria were applied to construct xylose/O2 based biofuel cell with good performance including enhanced operational stability. Thus, the approach described here could be explored for engineering of other enzymes for improving certain characters without three-dimensional structure identified by experimental methods. PMID- 26827778 TI - Cell structure, stiffness and permeability of freeze-dried collagen scaffolds in dry and hydrated states. AB - Scaffolds for tissue engineering applications should be highly permeable to support mass transfer requirements while providing a 3-D template for the encapsulated biological cells. High porosity and cell interconnectivity result in highly compliant scaffolds. Overstraining occurs easily with such compliant materials and can produce misleading results. In this paper, the cell structure of freeze-dried collagen scaffolds, in both dry and hydrated states, was characterised using X-ray tomography and 2-photon confocal microscopy respectively. Measurements have been made of the scaffold's Young's modulus using conventional mechanical testing and a customised see-saw testing configuration. Specific permeability was measured under constant pressure gradient and compared with predictions. The collagen scaffolds investigated here have a coarse cell size (~100-150 MUm) and extensive connectivity between adjacent cells (~10-30 MUm) in both dry and hydrated states. The Young's modulus is very low, of the order of 10 kPa when dry and 1 kPa when hydrated. There is only a single previous study concerning the specific permeability of (hydrated) collagen scaffolds, despite its importance in nutrient diffusion, waste removal and cell migration. The experimentally measured value reported here (5 * 10(-)(10)m(2)) is in good agreement with predictions based on Computational Fluid Dynamics simulation and broadly consistent with the Carman-Kozeny empirical estimate. It is however about three orders of magnitude higher than the single previously-reported value and this discrepancy is attributed at least partly to the high pressure gradient imposed in the previous study. STATEMENT OF SIGNIFICANCE: The high porosity and interconnectivity of tissue engineering scaffolds result in highly compliant structures (ie large deflections under low applied loads). Characterisation is essential if these scaffolds are to be systematically optimised. Scaffold overstraining during characterisation can lead to misleading results. In this study, the stiffness (in dry and hydrated states) and specific permeability of freeze-dried collagen scaffolds have been measured using techniques customised for low stiffness structures. The scaffold cell structure is investigated using X ray computed tomography, which has been applied previously to visualise such materials, without extracting any structural parameters or simulating fluid flow. These are carried out in this work. 2-photon confocal microscopy is used for the first time to study the structure in hydrated state. PMID- 26827779 TI - The effects of ethanol on the size-exclusion characteristics of type I dentin collagen to adhesive resin monomers. AB - During dentin bonding with etch-and-rinse adhesive systems, phosphoric acid etching of mineralized dentin solubilizes the mineral crystallites and replaces them with bound and unbound water. During the infiltration phase of dentin bonding, solvated adhesive resin comonomers are supposed to replace all of the unbound collagen water and polymerize into copolymers. A recently published review suggested that dental monomers are too large to enter and displace water from tightly-packed collagen molecules. Conversely, recent work from the authors' laboratory demonstrated that HEMA and TEGDMA freely equilibrate with water saturated dentin matrices. However, because adhesive blends are solvated in organic solvents, those solvents may remove enough free water to allow collagen molecules to come close enough to exclude adhesive monomer permeation. The present study analyzed the size-exclusion characteristics of dentin collagen, using a gel permeation-like column chromatography technique, filled with dentin powder instead of Sephadex beads as the stationary phase. The elution volumes of different sized test molecules, including adhesive resin monomers, studied in both water-saturated dentin, and again in ethanol-dehydrated dentin powder, showed that adhesive resin monomers can freely diffuse into both hydrated and dehydrated collagen molecules. Under these in vitro conditions, all free and some of the loosely-bound water seems to have been removed by ethanol. These results validate the concept that adhesive resin monomers can permeate tightly-bound water in ethanol-saturated collagen molecules during infiltration by etch-and rinse adhesives. STATEMENT OF SIGNIFICANCE: It has been reported that collagen molecules in dentin matrices are packed too close together to allow permeation of adhesive monomers between them. Resin infiltration, in this view, would be limited to extrafibrillar spaces. Our work suggests that monomers equilibrate with collagen water in both water and ethanol-saturated dentin matrices. PMID- 26827780 TI - Microstructural quantification of collagen fiber orientations and its integration in constitutive modeling of the porcine carotid artery. AB - BACKGROUND: Mechanical characteristics of vascular tissue may play a role in different arterial pathologies, which, amongst others, requires robust constitutive descriptions to capture the vessel wall's anisotropic and non-linear properties.Specifically, the complex 3D network of collagen and its interaction with other structural elements has a dominating effect of arterial properties at higher stress levels.The aim of this study is to collect quantitative collagen organization as well as mechanical properties to facilitate structural constitutive models for the porcine carotid artery.This helps the understanding of the mechanics of swine carotid arteries, being a standard in clinical hypothesis testing, in endovascular preclinical trials for example. METHOD: Porcine common carotid arteries (n=10) were harvested and used to (i) characterize the collagen fiber organization with polarized light microscopy, and (ii) the biaxial mechanical properties by inflation testing.The collagen organization was quantified by the Bingham orientation density function (ODF), which in turn was integrated in a structural constitutive model of the vessel wall.A one-layered and thick-walled model was used to estimate mechanical constitutive parameters by least-square fitting the recorded in vitro inflation test results.Finally, uniaxial data published elsewhere were used to validate the mean collagen organization described by the Bingham ODF. RESULTS: Thick collagen fibers, i.e.the most mechanically relevant structure, in the common carotid artery are dispersed around the circumferential direction.In addition, almost all samples showed two distinct families of collagen fibers at different elevation, but not azimuthal, angles.Collagen fiber organization could be accurately represented by the Bingham ODF (kappa1,2,3=[13.5,0.0,25.2] and kappa1,2,3=[14.7,0.0,26.6]; average error of about 5%), and their integration into a structural constitutive model captured the inflation characteristics of individual carotid artery samples.Specifically, only four mechanical parameters were required to reasonably (average error from 14% to 38%) cover the experimental data over a wide range of axial and circumferential stretches.However, it was critical to account for fibrilar links between thick collagen fibers.Finally, the mean Bingham ODF provide also good approximation to uniaxial experimental data. CONCLUSIONS: The applied structural constitutive model, based on individually measured collagen orientation densities, was able to capture the biaxial properties of the common carotid artery. Since the model required coupling amongst thick collagen fibers, the collagen fiber orientations measured from polarized light microscopy, alone, seem to be insufficient structural information. Alternatively, a larger dispersion of collagen fiber orientations, that is likely to arise from analyzing larger wall sections, could have had a similar effect, i.e. could have avoided coupling amongst thick collagen fibers. STATEMENT OF SIGNIFICANCE: The applied structural constitutive model, based on individually measured collagen orientation densities, was able to capture the biaxial and uniaxial properties of the common carotid artery. Since the model required coupling amongst thick collagen fibers, an effective orientation density that accounts for cross-links between the main collagen fibers has been porposed. The model provides a good approximation to the experimental data. PMID- 26827781 TI - DDPH, a novel antihypertensive agent, is a potential dual inhibitor of hepatic CYP2D and CYP3A. AB - DDPH (1-(2, 6-dimethylphenoxy)-2-(3, 4-dimethoxyphenylethylamino) propane hydrochloride) is a promising novel antihypertensive agent, with potent antihypertensive, neuroprotective and cardioprotective effects. This study aimed to investigate the effects of DDPH on the expression and activity of hepatic cytochrome P450 (CYP) isoforms and evaluate the metabolic drug-drug interactions of DDPH with propafenone. Our results showed that orally administered DDPH (12.5 50 mg/kg/d) for 7 days significantly inhibited CYP2D1 and CYP3A1 activity and mRNA and protein expression but weakly increased CYP1A2 activity and expression in rats. Enzyme kinetics studies showed that DDPH was a competitive inhibitor of CYP2D1 and mixed inhibitor of CYP3A1 in rat liver microsomes with Ki values of 3.70 +/- 0.42 MUM and 4.79 +/- 1.10 MUM respectively. With human liver microsomes, DDPH was a noncompetitive inhibitor of CYP2D6 (Ki = 0.85 +/- 0.06 MUM) and mixed inhibitor of CYP3A (Ki = 2.15 +/- 0.41 MUM). Further in vivo study showed that oral administration of DDPH (12.5-50 mg/kg/d) for 7 days in rats significantly increased the area under the plasma concentration-time curve (AUC) of propafenone by 25.4%-63.9%, with a concomitant decrease in the plasma clearance. In conclusion, the results indicated that DDPH inhibited CYP2D and CYP3A activities and down-regulated their protein expression and mRNA transcription. DDPH might cause metabolic drug-drug interactions through modulation of the activity and expression of CYP2D and CYP3A. This information could be important in the prediction of possible drug-drug interactions as well as for the effective therapy and the limitation of toxicity of DDPH in clinical practice. PMID- 26827782 TI - Phycocyanin ameliorates alloxan-induced diabetes mellitus in mice: Involved in insulin signaling pathway and GK expression. AB - The therapeutic potential and molecular mechanism of phycocyanin from Spirulina on alloxan-induced diabetes mice was investigated. In the experiment, 4-week treatment of phycocyanin at the dose of 100 and 200 mg/kg body weight in alloxan induced diabetes mice resulted in improved metrics in comparison with alloxan induced diabetes group. These metrics include blood glucose levels, glycosylated serum protein (GSP), glycosylated hemoglobin (GHb) and fasting serum insulin (FINS) levels. As its molecular mode of action, phycocyanin leads to the increase of IRS-1 tyrosine phosphorylation and the decrease of IRS-1 serine phosphorylation, also accompany with increased level of Akt phosphorylation on Ser473 in the liver and pancreas in diabetic mice. In addition, phycocyanin treatment enhanced the glucokinase (GK) level in the liver and pancreas, and the glucokinase regulatory protein (GKRP) level in the liver in diabetic mice. The results suggest that phycocyanin ameliorates alloxan-induced diabetes mellitus in mice by activating insulin signaling pathway and GK expression in pancreas and liver in diabetic mice. PMID- 26827783 TI - Successful cryopreservation of spermatogonia in critically endangered Manchurian trout (Brachymystax lenok). AB - Because of the lack of cryopreservation techniques for fish eggs and embryos, cryopreservation of fish spermatogonia and subsequent generation of eggs and sperm would be an exit strategy for the long-term preservation of genetic resources. This study aimed to optimize cryoprotectants, cooling rates, and thawing temperatures for slow freezing of spermatogonia from endangered Manchurian trout (Brachymystax lenok). Whole testes were frozen with a cryomedium containing 1.3 M methanol, 0.2 M trehalose, and 10% egg yolk at a cooling rate of -1 degrees C/min and then stored in liquid nitrogen for 2 days. After thawing at 30 degrees C in a water bath, testicular cells from thawed testes were intraperitoneally transplanted into allogeneic triploid hatchlings. Transplanted spermatogonia migrated toward and were incorporated into recipient gonads, where they underwent gametogenesis. Transplantation efficiency did not significantly differ between frozen and fresh testes, demonstrating that Manchurian trout spermatogonia can be successfully cryopreserved in liquid nitrogen. PMID- 26827784 TI - Amyloid imaging: Past, present and future perspectives. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by the gradual onset of dementia. The pathological hallmarks of the disease are Abeta amyloid plaques, and tau neurofibrillary tangles, along dendritic and synaptic loss and reactive gliosis. Functional and molecular neuroimaging techniques such as positron emission tomography (PET) using functional and molecular tracers, in conjuction with other Abeta and tau biomarkers in CSF, are proving valuable in the differential diagnosis of AD, as well as in establishing disease prognosis. With the advent of new therapeutic strategies, there has been an increasing application of these techniques for the determination of Abeta burden in vivo in the patient selection, evaluation of target engagement and assessment of the efficacy of therapeutic approaches aimed at reducing Abeta in the brain. PMID- 26827785 TI - Neuroimaging biomarkers in Alzheimer's disease and other dementias. AB - In vivo imaging of beta-amyloid (Abeta) has transformed the assessment of Abeta pathology and its changes over time, extending our insight into Abeta deposition in the brain by providing highly accurate, reliable, and reproducible quantitative statements of regional or global Abeta burden in the brain. This knowledge is essential for therapeutic trial recruitment and for the evaluation of anti-Abeta treatments. Although cross sectional evaluation of Abeta burden does not strongly correlate with cognitive impairment, it does correlate with cognitive (especially memory) decline and with a higher risk for conversion to AD in the aging population and MCI subjects. This suggests that Abeta deposition is a protracted pathological process starting well before the onset of symptoms. Longitudinal observations, coupled with different disease-specific biomarkers to assess potential downstream effects of Abeta are required to confirm this hypothesis and further elucidate the role of Abeta deposition in the course of Alzheimer's disease. PMID- 26827786 TI - Brain atrophy in Alzheimer's Disease and aging. AB - Thanks to its safety and accessibility, magnetic resonance imaging (MRI) is extensively used in clinical routine and research field, largely contributing to our understanding of the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). This review aims to provide a comprehensive overview of the main findings in AD and normal aging over the past twenty years, focusing on the patterns of gray and white matter changes assessed in vivo using MRI. Major progresses in the field concern the segmentation of the hippocampus with novel manual and automatic segmentation approaches, which might soon enable to assess also hippocampal subfields. Advancements in quantification of hippocampal volumetry might pave the way to its broader use as outcome marker in AD clinical trials. Patterns of cortical atrophy have been shown to accurately track disease progression and seem promising in distinguishing among AD subtypes. Disease progression has also been associated with changes in white matter tracts. Recent studies have investigated two areas often overlooked in AD, such as the striatum and basal forebrain, reporting significant atrophy, although the impact of these changes on cognition is still unclear. Future integration of different MRI modalities may further advance the field by providing more powerful biomarkers of disease onset and progression. PMID- 26827787 TI - Intervention for persistent atrial fibrillation: Prediction of treatment response. PMID- 26827788 TI - Molecular biomarkers of oxidative stress and role of dietary factors in gasoline station attendants. AB - Exposure to benzene promotes oxidative stress through the production of ROS, which can damage biological structures with the formation of new metabolites which can be used as markers of oxidant/antioxidant imbalance. This study aims to assess modifications in circulating levels of advanced oxidation protein products (AOPP), advanced glycation end-products (AGE) and serum reactive oxygen metabolites (ROMs) in a group of gasoline station attendants exposed to low-dose benzene and to evaluate the influence of antioxidant food intake on these biomarkers of oxidative stress. The diet adopted by the population examined consisted of compounds belonging to the classes of terpenoids, stilbenes and flavonoids, notably resveratrol, lycopene and apigenin. Ninety one gasoline station attendants occupationally exposed to benzene and 63 unexposed male office workers were recruited for this study. Urinary trans, trans-muconic acid (t,t-MA) concentration, determined to assess individual exposure level, resulted significantly higher in exposed workers. In subjects exposed to benzene, we observed a significant increase (p < 0.001) in ROMs and AOPP levels, which were also negatively correlated with fruit and vegetables consumption. By contrast, AGE did not show a significant increase and consequently any relation with antioxidant food intake. Only ROMs, representing a global biomarker of oxidative status, resulted correlated to t,t-MA levels (p < 0.01), probably due to low-dose exposure. Increase of ROS induced by reactive benzene metabolites may promote specific biochemical pathways with a major production of AOPP, which seem to represent a more sensitive biochemical marker of oxidative stress in workers exposed to benzene compared to AGE. Furthermore, this is the first study demonstrating ROMs increment in subject exposed to benzene. These biomarkers may be useful for screening purposes in gasoline station workers and other subjects exposed to low-dose benzene. Moreover, a diet rich in fruits and vegetables demonstrated an inverse association with the levels of oxidative stress markers, suggesting a protective role of antioxidant food intake in workers exposed to oxidant agents. PMID- 26827790 TI - Measuring access to liver transplantation: An overdue metric for center quality and performance. PMID- 26827789 TI - Toxicological evaluation of an Allium-based commercial product in a 90-day feeding study in Sprague-Dawley rats. AB - Proallium AP((r)) is a commercial Allium extract intended to be used in active food packaging as the antibacterial and antioxidant effects of some organosulfur compounds are well known. However, there is little information on its toxicity and the Scientific Committee on Food (UE) requires the safety assessment of substances used in food contact materials. Thus, the aim of this study was to conduct for the first time a subchronic oral toxicity study of Proallium AP((r)) with groups of 10 males and 10 females Sprague-Dawley rats fed a diet containing 0, 25, 100, 400 mg/kg/d for 90 days. No treatment-related clinical signs or mortality were noted. Besides, no treatment-related effects with regard to any of the toxicological biomarkers considered were observed, including biochemical, haematological and histopathology parameters. In conclusion, the non-observed adverse-effect-level (NOAEL) for Proallium AP((r)) in rats was determined to be a dietary dose of 400 mg/kg/d under the present experimental conditions, a value 500-fold higher than the exposure derived from its potential use in active packaging. PMID- 26827791 TI - Assessment of response to beta-blockers by expression of betaArr2 and RhoA/ROCK2 in antrum mucosa in cirrhotic patients. AB - BACKGROUND & AIMS: Non-selective beta-blockers (NSBB) are first choice for prevention of variceal bleeding. But possible deleterious effects in refractory ascites and frequent non-response are clinical drawbacks. Since levels of vasoactive proteins in antrum mucosa reflect vascular dysfunction in cirrhosis, these expression levels might also reflect hemodynamic response to NSBB. METHODS: Biopsies from the gastric and duodenal mucosa of 25 patients with cirrhosis were collected and the hepatic venous pressure gradient (HVPG) was measured before and after an acute propranolol challenge. Transcription and protein expression of Ras homolog family member A (RhoA), Rho-kinase (ROCK)2, beta-arrestin2 (betaArr2), endothelial nitric oxide synthase (eNOS) and the phosphorylation of downstream effectors VASP and moesin were analyzed using PCR and Western blot. Further 21 patients on NSBB were evaluated on their follow up for events of variceal bleeding defined as non-response. RESULTS: Ten patients showed HVPG <10mmHg, further seven patients showed significant hemodynamic response to NSBB, whereas eight patients were non-responders. The mucosal transcription of vasoactive proteins was higher in antrum mucosa compared to corpus and duodenum. The transcriptional levels of vasoactive proteins were higher in patients with HVPG >10mmHg and HVPG >16mmHg. Interestingly, mRNA levels of RhoA and ROCK2 were lower in patients with large varices at endoscopy. Moreover, RhoA and ROCK2 transcription correlated with the decrease of HVPG after acute NSBB challenge. Finally, acute and long-term non-responders showed lower expression of betaArr2 in antrum mucosa. CONCLUSION: This study shows for the first time that the expression of betaArr2 in antrum mucosa biopsies might reflect the hemodynamic response to NSBB and their long-term protective effect. This finding might offer an easy approach at upper endoscopy to facilitate the decision to treat with NSBB if varices are present. PMID- 26827792 TI - Mitochondrial DNA copy number and replication in reprogramming and differentiation. AB - Until recently, it was thought that the role of the mitochondrial genome was confined to encoding key proteins that generate ATP through the process of oxidative phosphorylation in the electron transfer chain. However, with increasing new evidence, it is apparent that the mitochondrial genome has a major role to play in a number of diseases and phenotypes. For example, mitochondrial variants and copy number have been implicated in the processes of fertilisation outcome and development and the onset of tumorigenesis. On the other hand, mitochondrial DNA (mtDNA) haplotypes have been implicated in a variety of diseases and most likely account for the adaptation that our ancestors achieved in order that they were fit for their environments. The mechanisms, which enable the mitochondrial genome to either protect or promote the disease phenotype, require further elucidation. However, there appears to be significant 'crosstalk' between the chromosomal and mitochondrial genomes that enable this to take place. One such mechanism is the regulation of DNA methylation by mitochondrial DNA, which is often perturbed in reprogrammed cells that have undergone dedifferentiation and affects mitochondrial DNA copy number. Furthermore, it appears that the mitochondrial genome interacts with the chromosomal genome to regulate the transcription of key genes at certain stages during development. Additionally, the mitochondrial genome can accumulate a series of mtDNA variants, which can lead to diseases such as cancer. It is likely that a combination of certain mitochondrial variants and aberrant patterns of mtDNA copy number could indeed account for many diseases that have previously been unaccounted for. This review focuses on the role that the mitochondrial genome plays especially during early stages of development and in cancer. PMID- 26827793 TI - Inherited PTEN mutations and the prediction of phenotype. AB - PTEN has been heavily studied due to its role as a tumour suppressor and as a core inhibitory component of the phosphoinositide 3-kinase (PI3K) signalling network. It is a broadly expressed phosphatase which displays complexity and diversity in both its functions and regulation and accordingly, in the laboratory numerous classes of functionally distinct mutations have been generated. Inherited loss of function mutations in the PTEN gene were originally identified in sufferers of Cowden disease, but later shown to associate with more diverse human pathologies, mostly relating to cell and tissue overgrowth, leading to the use of the broader term, PTEN Hamartoma Tumour Syndrome. Recent phenotypic analysis of clinical cohorts of PTEN mutation carriers, combined with laboratory studies of the consequences of these mutations implies that stable catalytically inactive PTEN mutants may lead to the most severe phenotypes, and conversely, that mutants retaining partial function associate more frequently with a milder phenotype, with autism spectrum disorder often being diagnosed. Future work will be needed to confirm and to refine these genotype-phenotype relationships and convert this developing knowledge into improved patient management and potentially treatment with emerging drugs which target the PI3K pathway. PMID- 26827794 TI - Preliminary analysis showed country-specific gut resistome based on 1,267 feces samples. AB - Gut microbiota (GM) plays an important role in drug metabolism and absorption. Ever-increasing antibiotic use could result in high accumulation of antibiotic resistance genes (ARGs) in GM, which will reduce the recovery rate of many infectious diseases. The foci of this study is to unravel ARG distribution in GM of 1267 subjects from four countries in three continents, by annotation with ARDB (Antibiotic Resistance Genes Database) and ARG-ANNOT database. Analysis results showed that all three continents had similar ARG composition, but Chinese had the highest ARG relative abundance, followed by American and European. This is possibly attributed to delayed policies on antibiotic use in China, and restrict legislation in Europe. Delivery time and application scope are proportional to ARG enrichment in GM. Findings in this study indicate that ARG accumulation could be associated with government policies on antibiotic use, and corresponding delivery time and application scope, which will be a significant reference to control antibiotic abuse. PMID- 26827795 TI - Study of microRNAs-21/221 as potential breast cancer biomarkers in Egyptian women. AB - microRNAs (miRNAs) play an important role in cancer prognosis. They are small molecules, approximately 17-25 nucleotides in length, and their high stability in human serum supports their use as novel diagnostic biomarkers of cancer and other pathological conditions. In this study, we analyzed the expression patterns of miR-21 and miR-221 in the serum from a total of 100 Egyptian female subjects with breast cancer, fibroadenoma, and healthy control subjects. Using microarray-based expression profiling followed by real-time polymerase chain reaction validation, we compared the levels of the two circulating miRNAs in the serum of patients with breast cancer (n=50), fibroadenoma (n=25), and healthy controls (n=25). The miRNA SNORD68 was chosen as the housekeeping endogenous control. We found that the serum levels of miR-21 and miR-221 were significantly overexpressed in breast cancer patients compared to normal controls and fibroadenoma patients. Receiver Operating Characteristic (ROC) curve analysis revealed that miR-21 has greater potential in discriminating between breast cancer patients and the control group, while miR-221 has greater potential in discriminating between breast cancer and fibroadenoma patients. Classification models using k-Nearest Neighbor (kNN), Naive Bayes (NB), and Random Forests (RF) were developed using expression levels of both miR-21 and miR-221. Best classification performance was achieved by NB Classification models, reaching 91% of correct classification. Furthermore, relative miR-221 expression was associated with histological tumor grades. Therefore, it may be concluded that both miR-21 and miR-221 can be used to differentiate between breast cancer patients and healthy controls, but that the diagnostic accuracy of serum miR-21 is superior to miR-221 for breast cancer prediction. miR-221 has more diagnostic power in discriminating between breast cancer and fibroadenoma patients. The overexpression of miR-221 has been associated with the breast cancer grade. We also demonstrated that the combined expression of miR-21 and miR-221can be successfully applied as breast cancer biomarkers. PMID- 26827796 TI - Genomic characterization of Pasteurella multocida HB01, a serotype A bovine isolate from China. AB - Pasteurella multocida infects various domestic and feral animals, generally causing clinical disease. To investigate P. multocida disease in cattle, we sequenced the complete genome of P. multocida HB01 (GenBank accession CP006976), a serotype A organism isolated from a cow in China. The genome is composed of a single circular chromosome of 2,416,068 base pairs containing 2212 protein-coding sequences, 6 ribosomal rRNA operons, and 56 tRNA genes. The present study confirms that P. multocida HB01 possesses a more complete metabolic pathway with an intact trichloroacetic acid cycle for anabolism compared with A. pleuropneumoniae and Haemophilus parasuis. This is the first time that this metabolic mechanism of P. multocida has been described. We also identified a full spectrum of genes related to known virulence factors of P. multocida. The differences in virulence factors between strains of different serotypes and origins were also compared. This comprehensive comparative genome analysis will help in further studies of the metabolic pathways, genetic basis of serotype, and virulence of P. multocida. PMID- 26827797 TI - mRNA GPR162 changes are associated with decreased food intake in rat, and its human genetic variants with impairments in glucose homeostasis in two Swedish cohorts. AB - G protein-coupled receptors (GPCRs) are a class of integral membrane proteins mediating intercellular interactions of fundamental physiological importance for survival including regulation of food intake, blood pressure, and hormonal sensing signaling, among other roles. Homeostatic alterations in the physiological status of GPCRs are often associated with underlying causes of disease, and to date, several orphan GPCRs are still uncharacterized. Findings from our previous study demonstrate that the Rhodopsin family protein GPR162 is widely expressed in GABAergic as well as other neurons within the mouse hippocampus, whereas extensive expression is observed in hypothalamus, amygdala, and ventral tegmental area, regions strictly interconnected and involved in the regulation of energy homeostasis and hedonic feeding. In this study, we provide a further anatomical characterization of GPR162 in mouse brain via in situ hybridization as well as detailed mRNA expression in a panel of rat tissues complementing a specie-specific mapping of the receptor. We also provide an attempt to demonstrate a functional implication of GPR162 in food intake-related behavior via antisense knockdown studies. Furthermore, we performed human genetic studies in which for the first time, variants of the GPR162 gene were associated with impairments in glucose homeostasis. PMID- 26827798 TI - A Challenging Case of Splenomegaly and Refractory Thrombocytopenia. PMID- 26827799 TI - Important Study Adds to Understanding of the Pathophysiology of Visceral Hypersensitivity but Raises More Questions Than it Answers. PMID- 26827800 TI - An Unusual Cause of Right Upper Quadrant Pain in a Patient With Prior Liver Transplantation for Primary Sclerosing Cholangitis. PMID- 26827801 TI - An Unusual Cause of Severe Chest Pain. PMID- 26827802 TI - Reply. PMID- 26827803 TI - An Unusual Cause of Chronic Nausea and Abdominal Pain. PMID- 26827804 TI - Unexpected Connection With a Diverticular Abscess. PMID- 26827805 TI - Age-Related Immunoreactivity to Gluten Peptides in Celiac Disease. PMID- 26827806 TI - Epigastric Pain in a Patient With Nodular Regenerative Hyperplasia. PMID- 26827807 TI - Public health perspectives from the biggest human mass gathering on earth: Kumbh Mela, India. AB - Mass gathering events pose critical health challenges, especially for the control of diseases. The rising population, better connectivity, and scope of travel have increased the frequency and magnitude of mass gatherings and underscore the need to shift the discourse from reacting to the public health issues they throw up to taking active steps in preventing them based on evidence through research. The Kumbh Mela is a religious event in India that constitutes the largest number of people gathered at a specific place and at a specific time. It is older than the Hajj by centuries, yet the public health aspects related to this event, which is held every 3 years, have not been fully studied. Understanding the Kumbh Mela can highlight the health challenges faced and provide crucial lessons for the management of mass gatherings. This investigation used the Kumbh Mela in the city of Allahabad as a case study to describe the health problems and the efforts taken to manage them. In-depth studies of the Kumbh Mela in the future are required to generate evidence for context-specific measures to address the complex health challenges of mass gatherings. PMID- 26827809 TI - Distortion products in auditory fMRI research: Measurements and solutions. AB - Nonlinearities in the cochlea can introduce audio frequencies that are not present in the sound signal entering the ear. Known as distortion products (DPs), these added frequencies complicate the interpretation of auditory experiments. Sound production systems also introduce distortion via nonlinearities, a particular concern for fMRI research because the Sensimetrics earphones widely used for sound presentation are less linear than most high-end audio devices (due to design constraints). Here we describe the acoustic and neural effects of cochlear and earphone distortion in the context of fMRI studies of pitch perception, and discuss how their effects can be minimized with appropriate stimuli and masking noise. The amplitude of cochlear and Sensimetrics earphone DPs were measured for a large collection of harmonic stimuli to assess effects of level, frequency, and waveform amplitude. Cochlear DP amplitudes were highly sensitive to the absolute frequency of the DP, and were most prominent at frequencies below 300 Hz. Cochlear DPs could thus be effectively masked by low frequency noise, as expected. Earphone DP amplitudes, in contrast, were highly sensitive to both stimulus and DP frequency (due to prominent resonances in the earphone's transfer function), and their levels grew more rapidly with increasing stimulus level than did cochlear DP amplitudes. As a result, earphone DP amplitudes often exceeded those of cochlear DPs. Using fMRI, we found that earphone DPs had a substantial effect on the response of pitch-sensitive cortical regions. In contrast, cochlear DPs had a small effect on cortical fMRI responses that did not reach statistical significance, consistent with their lower amplitudes. Based on these findings, we designed a set of pitch stimuli optimized for identifying pitch-responsive brain regions using fMRI. These stimuli robustly drive pitch-responsive brain regions while producing minimal cochlear and earphone distortion, and will hopefully aid fMRI researchers in avoiding distortion confounds. PMID- 26827808 TI - Iron depletion suppresses mTORC1-directed signalling in intestinal Caco-2 cells via induction of REDD1. AB - Iron is an indispensable micronutrient that regulates many aspects of cell function, including growth and proliferation. These processes are critically dependent upon signalling via the mammalian or mechanistic target of rapamycin complex 1 (mTORC1). Herein, we test whether iron depletion induced by cell incubation with the iron chelator, deferoxamine (DFO), mediates its effects on cell growth through mTORC1-directed signalling and protein synthesis. We have used Caco-2 cells, a well-established in vitro model of human intestinal epithelia. Iron depletion increased expression of iron-regulated proteins (TfR, transferrin receptor and DMT1, divalent metal transporter, as predicted, but it also promoted a marked reduction in growth and proliferation of Caco-2 cells. This was strongly associated with suppressed mTORC1 signalling, as judged by reduced phosphorylation of mTOR substrates, S6K1 and 4E-BP1, and diminished protein synthesis. The reduction in mTORC1 signalling was tightly coupled with increased expression and accumulation of REDD1 (regulated in DNA damage and development 1) and reduced phosphorylation of Akt and TSC2. The increase in REDD1 abundance was rapidly reversed upon iron repletion of cells but was also attenuated by inhibitors of gene transcription, protein phosphatase 2A (PP2A) and by REDD1 siRNA--strategies that also antagonised the loss in mTORC1 signalling associated with iron depletion. Our findings implicate REDD1 and PP2A as crucial regulators of mTORC1 activity in iron-depleted cells and indicate that their modulation may help mitigate atrophy of the intestinal mucosa that may occur in response to iron deficiency. PMID- 26827810 TI - Is bigger always better? The importance of cortical configuration with respect to cognitive ability. AB - General cognitive ability (GCA) has substantial explanatory power for behavioral and health outcomes, but its cortical substrate is still not fully established. GCA is highly polygenic and research to date strongly suggests that its cortical substrate is highly polyregional. We show in map-based and region-of-interest based analyses of adult twins that a complex cortical configuration underlies GCA. Having relatively greater surface area in evolutionary and developmentally high-expanded prefrontal, lateral temporal, and inferior parietal regions is positively correlated with GCA, whereas relatively greater surface area in low expanded occipital, medial temporal, and motor cortices is negatively correlated with GCA. Essentially the opposite pattern holds for relative cortical thickness. The phenotypic positive-to-negative gradients in our cortical-GCA association maps were largely driven by a similar pattern of genetic associations. The patterns are consistent with regional cortical stretching whereby relatively greater surface area is related to relatively thinner cortex in high-expanded regions. Thus, the typical "bigger is better" view does not adequately capture cortical-GCA associations. Rather, cognitive ability is influenced by complex configurations of cortical development patterns that are strongly influenced by genetic factors. Optimal cognitive ability appears to be driven both by the absolute size and the polyregional configuration of the entire cortex rather than by small, circumscribed regions. PMID- 26827812 TI - Effects of transcranial direct current stimulation on the functional coupling of the sensorimotor cortical network. AB - Transcranial direct current stimulation (tDCS) is well established-among the non invasive brain stimulation techniques-as a method to modulate brain excitability. Polarity-dependent modulations of membrane potentials are detected after the application of anodal and cathodal stimulation, leading to changes in the electrical activity of the neurons. The main aim of the present study was to test the hypothesis that tDCS can affect-in a polarity-specific manner-the functional coupling of the sensorimotor areas during the eyes-open resting condition as revealed by total EEG coherence (i.e., coherence across the average of all combinations of the electrode pairs placed around the stimulation electrode). The changes in the total EEG coherence were evaluated pre-, during, and post-anodal and cathodal tDCS. While no differences were observed in the connectivity characteristics of the two pre-stimulation periods, a connectivity increase was observed in the alpha 2 band in the post-anodal tDCS with respect to pre-anodal and post-cathodal tDCS. The present study suggests that a specific approach based on the analyses of the functional coupling of EEG rhythms might enhance understanding of tDCS-induced effects on cortical connectivity. Moreover, this result suggests that anodal tDCS could possibly modify cortical connectivity more effectively with respect to cathodal tDCS. PMID- 26827811 TI - Predicting haemodynamic networks using electrophysiology: The role of non-linear and cross-frequency interactions. AB - Understanding the electrophysiological basis of resting state networks (RSNs) in the human brain is a critical step towards elucidating how inter-areal connectivity supports healthy brain function. In recent years, the relationship between RSNs (typically measured using haemodynamic signals) and electrophysiology has been explored using functional Magnetic Resonance Imaging (fMRI) and magnetoencephalography (MEG). Significant progress has been made, with similar spatial structure observable in both modalities. However, there is a pressing need to understand this relationship beyond simple visual similarity of RSN patterns. Here, we introduce a mathematical model to predict fMRI-based RSNs using MEG. Our unique model, based upon a multivariate Taylor series, incorporates both phase and amplitude based MEG connectivity metrics, as well as linear and non-linear interactions within and between neural oscillations measured in multiple frequency bands. We show that including non-linear interactions, multiple frequency bands and cross-frequency terms significantly improves fMRI network prediction. This shows that fMRI connectivity is not only the result of direct electrophysiological connections, but is also driven by the overlap of connectivity profiles between separate regions. Our results indicate that a complete understanding of the electrophysiological basis of RSNs goes beyond simple frequency-specific analysis, and further exploration of non-linear and cross-frequency interactions will shed new light on distributed network connectivity, and its perturbation in pathology. PMID- 26827813 TI - Measuring the cortical correlation structure of spontaneous oscillatory activity with EEG and MEG. AB - Power correlations of orthogonalized signals have recently been introduced for MEG as a powerful tool to non-invasively investigate functional connectivity in the human brain. Little is known about the applicability of this approach to EEG, and how compatible the results are between EEG and MEG. To address this, we systematically compared power correlations of simultaneously recorded and source co-registered 64-channel EEG and 275-channel MEG in resting human subjects. For both modalities, connectivity peaked at around 16 Hz. For this frequency range, seed-based correlation maps showed comparable patterns across modalities, with generally more distinct patterns for MEG. A brain-wide pattern correlation analysis also revealed maximum similarity around 16 Hz. Correcting for different signal-to-noise ratio (SNR) across frequencies and modalities revealed pattern correlation between modalities close to one across a broad frequency range from 1 to 32 Hz and only slightly smaller for higher frequencies. The decrease above 32 Hz likely reflected higher susceptibility to muscle artifacts for EEG than for MEG. Our results show that power correlation of orthogonalized signals is feasible for studying functional connectivity with 64-channel EEG. Furthermore, besides differences in SNR, for frequencies from about 8 to 32 Hz, EEG and MEG measure the same correlation patterns across the entire brain. PMID- 26827814 TI - Cue-dependent circuits for illusory contours in humans. AB - Objects' borders are readily perceived despite absent contrast gradients, e.g. due to poor lighting or occlusion. In humans, a visual evoked potential (VEP) correlate of illusory contour (IC) sensitivity, the "IC effect", has been identified with an onset at ~90 ms and generators within bilateral lateral occipital cortices (LOC). The IC effect is observed across a wide range of stimulus parameters, though until now it always involved high-contrast achromatic stimuli. Whether IC perception and its brain mechanisms differ as a function of the type of stimulus cue remains unknown. Resolving such will provide insights on whether there is a unique or multiple solutions to how the brain binds together spatially fractionated information into a cohesive perception. Here, participants discriminated IC from no-contour (NC) control stimuli that were either comprised of low-contrast achromatic stimuli or instead isoluminant chromatic contrast stimuli (presumably biasing processing to the magnocellular and parvocellular pathways, respectively) on separate blocks of trials. Behavioural analyses revealed that ICs were readily perceived independently of the stimulus cue--i.e. when defined by either chromatic or luminance contrast. VEPs were analysed within an electrical neuroimaging framework and revealed a generally similar timing of IC effects across both stimulus contrasts (i.e. at ~90 ms). Additionally, an overall phase shift of the VEP on the order of ~30 ms was consistently observed in response to chromatic vs. luminance contrast independently of the presence/absence of ICs. Critically, topographic differences in the IC effect were observed over the ~110-160 ms period; different configurations of intracranial sources contributed to IC sensitivity as a function of stimulus contrast. Distributed source estimations localized these differences to LOC as well as V1/V2. The present data expand current models by demonstrating the existence of multiple, cue-dependent circuits in the brain for generating perceptions of illusory contours. PMID- 26827815 TI - Individual attentional selection capacities are reflected in interhemispheric connectivity of the parietal cortex. AB - Modelling psychophysical data using the Theory of Visual Attention (TVA) allows for a quantification of attentional sub-processes, such as the resolution of competition amongst multiple stimuli by top-down control signals for target selection (TVA-parameter alpha). This fMRI study investigated the neural correlates of alpha by comparing activity differences and changes of effective connectivity between conditions where a target was accompanied by a distractor or by a second target. Twenty-five participants performed a partial report task inside the MRI scanner. The left angular gyrus (ANG), medial frontal, and posterior cingulate cortex showed higher activity when a target was accompanied by a distractor as opposed to a second target. The reverse contrast yielded activation of a bilateral fronto-parietal network, the anterior insula, anterior cingulate cortex, and left inferior occipital gyrus. A psychophysiological interaction analysis revealed that the connectivity between left ANG and the left and right supramarginal gyrus (SMG), left anterior insula, and right putamen was enhanced in the target-distractor condition in participants with worse attentional top-down control. Dynamic causal modelling suggested that the connection from left ANG to right SMG during distractor presence was modulated by alpha. Our data show that interindividual differences in attentional processing are reflected in changes of effective connectivity without significant differences in activation strength of network nodes. PMID- 26827816 TI - Statistical machine learning to identify traumatic brain injury (TBI) from structural disconnections of white matter networks. AB - Identifying diffuse axonal injury (DAI) in patients with traumatic brain injury (TBI) presenting with normal appearing radiological MRI presents a significant challenge. Neuroimaging methods such as diffusion MRI and probabilistic tractography, which probe the connectivity of neural networks, show significant promise. We present a machine learning approach to classify TBI participants primarily with mild traumatic brain injury (mTBI) based on altered structural connectivity patterns derived through the network based statistical analysis of structural connectomes generated from TBI and age-matched control groups. In this approach, higher order diffusion models were used to map white matter connections between 116 cortical and subcortical regions. Tracts between these regions were generated using probabilistic tracking and mean fractional anisotropy (FA) measures along these connections were encoded in the connectivity matrices. Network-based statistical analysis of the connectivity matrices was performed to identify the network differences between a representative subset of the two groups. The affected network connections provided the feature vectors for principal component analysis and subsequent classification by random forest. The validity of the approach was tested using data acquired from a total of 179 TBI patients and 146 controls participants. The analysis revealed altered connectivity within a number of intra- and inter-hemispheric white matter pathways associated with DAI, in consensus with existing literature. A mean classification accuracy of 68.16%+/-1.81% and mean sensitivity of 80.0%+/-2.36% were achieved in correctly classifying the TBI patients evaluated on the subset of the participants that was not used for the statistical analysis, in a 10-fold cross-validation framework. These results highlight the potential for statistical machine learning approaches applied to structural connectomes to identify patients with diffusive axonal injury. PMID- 26827817 TI - Neural mechanisms of the nucleus accumbens circuit in reward and aversive learning. AB - The basal ganglia are key neural substrates not only for motor function, but also cognitive functions including reward and aversive learning. Critical for these processes are the functional role played by two projection neurons within nucleus accumbens (NAc); the D1- and D2-expressing neurons. Recently, we have developed a novel reversible neurotransmission blocking technique that specifically blocks neurotransmission from NAc D1- and D2-expressing neurons, allowing for in vivo analysis. In this review, we outline the functional dissociation of NAc D1- and D2-expressing neurons of the basal ganglia in reward and aversive learning, as well as drug addiction. These studies have revealed the importance of activation of NAc D1 receptors for reward learning and drug addiction, and inactivation of NAc D2 receptors for aversive learning and flexibility. Based on these findings, we propose a neural mechanism, in which dopamine neurons in the ventral tegmental area that send inputs to the NAc work as a switch between D1- and D2-expressing neurons. These basal ganglia neural mechanisms will give us new insights into the pathophysiology of neuropsychiatric diseases. PMID- 26827818 TI - Pair exposure with conspecific during fear conditioning induces the link between freezing and passive avoidance behaviors in rats. AB - Social factor plays an important role in dealing with posttraumatic stress disorder related to excessive physiological fear response and insufficient fear memory extinction of the brain. However, although social circumstances occurred not only during contextual retrieval but also during fear conditioning, most previous studies focused on the advantageous aspects of social buffering in fear retrieval period. To demonstrate the association between fear responses and fear memory from social stimuli during fear conditioning, pair exposed rats with conspecific as social buffering were subjected to a fear conditioning of passive avoidance test to evaluate memory function and freezing behavior. Whereas single exposed rats showed the significant increase of freezing behaviors and passive avoidance behaviors compared to control rats, pair exposed rats showed significant alleviation of the freezing behaviors and passive avoidance behaviors compared to single exposed rats. Furthermore, we determined a significant correlation between freezing and passive avoidance behavioral alteration in pair exposed rats. Taken together, we suggest that pair exposure with conspecific during fear conditioning helps to cope with both freezing response and fear memory systems and their reciprocal interaction has a crucial potential as a resource for the relief of unreasonable stress responses in posttraumatic stress disorder. PMID- 26827819 TI - Maternal Obesity: Lifelong Metabolic Outcomes for Offspring from Poor Developmental Trajectories During the Perinatal Period. AB - The prevalence of obesity in women of reproductive age is increasing in developed and developing countries around the world. Human and animal studies indicate that maternal obesity adversely impacts both maternal health and offspring phenotype, predisposing them to chronic diseases later in life including obesity, dyslipidemia, type 2 diabetes mellitus, and hypertension. Several mechanisms act together to produce these adverse health effects including programming of hypothalamic appetite-regulating centers, increasing maternal, fetal and offspring glucocorticoid production, changes in maternal metabolism and increasing maternal oxidative stress. Effective interventions during human pregnancy are needed to prevent both maternal and offspring metabolic dysfunction due to maternal obesity. This review addresses the relationship between maternal obesity and its negative impact on offspring development and presents some maternal intervention studies that propose strategies to prevent adverse offspring metabolic outcomes. PMID- 26827820 TI - A redox proteomics approach to investigate the mode of action of nanomaterials. AB - Numbers of engineered nanomaterials (ENMs) are steadily increasing. Therefore, alternative testing approaches with reduced costs and high predictivity suitable for high throughput screening and prioritization are urgently needed to ensure a fast and effective development of safe products. In parallel, extensive research efforts are targeted to understanding modes of action of ENMs, which may also support the development of new predictive assays. Oxidative stress is a widely accepted paradigm associated with different adverse outcomes of ENMs. It has frequently been identified in in vitro and in vivo studies and different assays have been developed for this purpose. Fluorescent dye based read-outs are most frequently used for cell testing in vitro but may be limited due to possible interference of the ENMs. Recently, other assays have been put forward such as acellular determination of ROS production potential using methods like electron spin resonance, antioxidant quantification or the use of specific sensors. In addition, Omics based approaches have gained increasing attention. In particular, redox proteomics can combine the assessment of oxidative stress with the advantage of getting more detailed mechanistic information. Here we propose a comprehensive testing strategy for assessing the oxidative stress potential of ENMs, which combines acellular methods and fast in vitro screening approaches, as well as a more involved detailed redox proteomics approach. This allows for screening and prioritization in a first tier and, if required, also for unraveling mechanistic details down to compromised signaling pathways. PMID- 26827821 TI - Nephron segment specific microRNA biomarkers of pre-clinical drug-induced renal toxicity: Opportunities and challenges. AB - Drug-induced nephrotoxicity is a common drug development complication for pharmaceutical companies. Sensitive, specific, translatable and non-invasive biomarkers of renal toxicity are urgently needed to diagnose nephron segment specific injury. The currently available gold standard biomarkers for nephrotoxicity are not kidney-specific, lack sensitivity for early detection, and are not suitable for renal damage localization (glomerular vs tubulointerstitial injury). MicroRNAs (miRNAs) are increasingly gaining momentum as promising biomarkers of various organ toxicities, including drug induced renal injury. This is mostly due to their stability in easily accessible biofluids, ease of developing nucleic acids detection compared to protein detection assays, as well as their interspecies translatability. Increasing concordance of miRNA findings by standardizing methodology most suitable for their detection and quantitation, as well as characterization of their expression pattern in a cell type specific manner, will accelerate progress toward validation of these miRNAs as biomarkers in pre-clinical, and clinical settings. This review aims to highlight the current pre-clinical findings surrounding miRNAs as biomarkers in two important segments of the nephron, the glomerulus and tubules. PMID- 26827823 TI - Pathophysiologic mechanisms of biomedical nanomaterials. AB - Nanomaterials (NMs) have been widespread used in biomedical fields, daily consuming, and even food industry. It is crucial to understand the safety and biomedical efficacy of NMs. In this review, we summarized the recent progress about the physiological and pathological effects of NMs from several levels: protein-nano interface, NM-subcellular structures, and cell-cell interaction. We focused on the detailed information of nano-bio interaction, especially about protein adsorption, intracellular trafficking, biological barriers, and signaling pathways as well as the associated mechanism mediated by nanomaterials. We also introduced related analytical methods that are meaningful and helpful for biomedical effect studies in the future. We believe that knowledge about pathophysiologic effects of NMs is not only significant for rational design of medical NMs but also helps predict their safety and further improve their applications in the future. PMID- 26827822 TI - Partial contribution of the Keap1-Nrf2 system to cadmium-mediated metallothionein expression in vascular endothelial cells. AB - Cadmium is an environmental electrophile that modifies protein reactive thiols such as Kelch-like ECH-associated protein 1 (Keap1), a negative regulator of nuclear factor-erythroid 2-related factor 2 (Nrf2). In the present study, we investigated a role of the Keap1-Nrf2 system in cellular response to cadmium in vascular endothelial cells. Exposure of bovine aortic endothelial cells to cadmium resulted in modification of Keap1 and Nrf2 activation, thereby up regulating not only its typical downstream proteins but also metallothionein-1/2. Experiments with siRNA-mediated knockdown of Nrf2 or Keap1 supported participation of the Keap1-Nrf2 system in the modulation of metallothionein-1/2 expression. Furthermore, chromatin immunoprecipitation assay showed that Nrf2 was recruited to the antioxidant response element of the promoter region of the bovine metallothionein-2 gene in the presence of cadmium. These results suggest that the transcription factor Nrf2 plays, at least in part, a role in the changes in metallothionein expression mediated by exposure to cadmium. PMID- 26827826 TI - MicroRNA-26b suppresses the metastasis of non-small cell lung cancer by targeting MIEN1 via NF-kappaB/MMP-9/VEGF pathways. AB - MicroRNAs (miRNAs) are involved in tumor initiation and progression. MiR-26b was reported to be significantly downregulated in non-small cell lung cancer (NSCLC). However, the underlying mechanisms of miR-26b involvement in the development and progression of NSCLC remains poorly understood. In the present study, we report that miR-26b suppresses cell metastasis in NSCLC through targeting migration and invasion enhancer 1 (MIEN1). We found that miR-26b was significantly downregulated and MIEN1 was significantly upregulated in both NSCLC tissues and cells lines. The expression levels of miR-26b were negatively related to those of MIEN1 mRNA in clinical NSCLC tissues. Furthermore, MIEN1 was confirmed to be a direct target of miR-26b by dual-luciferase reporter assay and MIEN1 expression was downregulated by miR-26b in NSCLC cells. In terms of function, transwell and wound healing assays demonstrated that the miR-26b remarkably inhibited invasion and migration of NSCLC cells, which was simulated by siRNA knockdown of MIEN1 and reversed by pcDNA/MIEN1 overexpression of MIEN1. Finally, we found that miR-26b could regulate NF-kappaB/MMP-9/VEGF pathway in NSCLC cells. In conclusion, this study revealed that miR-26b suppresses NSCLC metastasis by targeting MIEN1 via NF kappaB/MMP-9/VEGF pathways, implicating a potential prognostic biomarker and therapeutic target for NSCLC treatment. PMID- 26827824 TI - Oxidative stress and proteasome inhibitors in multiple myeloma. AB - Multiple myeloma is a form of plasma cell neoplasm that accounts for approximately 10% of all hematological malignancies. Recently, several novel drugs have been discovered that almost doubled the overall survival of multiple myeloma patients. One of these drugs, the first-in-class proteasome inhibitor bortezomib (Velcade) has demonstrated remarkable response rates in multiple myeloma patients, and yet, currently this disease remains incurable. The major factor undermining the success of multiple myeloma treatment is a rapidly emerging resistance to the available therapy. Thus, the development of stand alone or adjuvant anti-myeloma agents becomes of paramount importance. Overproduction of intracellular reactive oxygen species (ROS) often accompanies malignant transformation due to oncogene activation and/or enhanced metabolism in tumor cells. As a result, these cells possess higher levels of ROS and lower levels of antioxidant molecules compared to their normal counterparts. Unbalanced production of ROS leads to oxidative stress which, if left unchecked, could be toxic for the cell. In multiple myeloma cells where high rates of immunoglobulin synthesis is an additional factor contributing to overproduction of ROS, further induction of oxidative stress can be an effective strategy to cope with this disease. Here we will review the available data on the role of oxidative stress in the cytotoxicity of proteasome inhibitors and the use of ROS-inducing compounds as anti-myeloma agents. PMID- 26827827 TI - iTRAQ-based chromatin proteomic screen reveals CHD4-dependent recruitment of MBD2 to sites of DNA damage. AB - Many DNA repair proteins can be recruited to DNA damage sites upon genotoxic stress. In order to search potential DNA repair proteins involved in cellular response to mitomycin C treatment, we utilized a quantitative proteome to uncover proteins that manifest differentially enrichment in the chromatin fraction after DNA damage. 397 proteins were identified, among which many factors were shown to be involved in chromatin modification and DNA repair by GO analysis. Specifically, methyl-CpG-binding domain protein 2 (MBD2) is revealed to be recruited to DNA damage sites after laser microirradiation, which was mediated through MBD domain and MBD2 C-terminus. Additionally, the recruitment of MBD2 is dependent on poly (ADP-ribose) and chromodomain helicase DNA-binding protein 4 (CHD4). Moreover, knockdown of MBD2 by CRISPR-Cas9 technique results in MMC sensitivity in mammalian cells. PMID- 26827828 TI - Prenatal exposure to dexamethasone disturbs sex-determining gene expression and fetal testosterone production in male embryos. AB - Prenatal stress is known to cause intrauterine fetal growth retardation, and is also associated with various long-term effects in the form of metabolic and neurodevelopmental diseases in adults. Many of the diseases associated with prenatal stress exhibit a sex bias. Perturbations and vulnerability to prenatal stress are often more profound in males, but the mechanisms responsible for this relationship are not clear. We have previously shown that administration of the synthetic glucocorticoid, dexamethasone (Dex), at embryonic days 7.5, 8.5, and 9.5, induces embryonic growth restriction in a sex-dependent manner in a mouse model. Here we examined the effect of prenatal exposure to Dex on gonadal development. During male gonadal development, sex-determining genes, such as Sry, Sox9, and other downstream genes, were found to be dysregulated in response to prenatal Dex, whereas the genes for the ovarian pathway were affected to a lesser degree in females. In addition, fetal testosterone concentrations were decreased by prenatal exposure to Dex, in parallel with reduced numbers of 3beta hydroxysteroid dehydrogenase (3beta-HSD)-positive cells in the embryonic testis. These results show that prenatal exposure to Dex differentially influences male versus female on the gene expression and hormone production during sex determination. We believe these studies provide valuable insights into possible mechanisms responsible for sex-specific responses to prenatal stress. PMID- 26827829 TI - Toward the International Classification of Functioning, Disability and Health (ICF) Rehabilitation Set: A Minimal Generic Set of Domains for Rehabilitation as a Health Strategy. AB - OBJECTIVE: To develop a comprehensive set of the International Classification of Functioning, Disability and Health (ICF) categories as a minimal standard for reporting and assessing functioning and disability in clinical populations along the continuum of care. The specific aims were to specify the domains of functioning recommended for an ICF Rehabilitation Set and to identify a minimal set of environmental factors (EFs) to be used alongside the ICF Rehabilitation Set when describing disability across individuals and populations with various health conditions. DESIGN: Secondary analysis of existing data sets using regression methods (Random Forests and Group Lasso regression) and expert consultations. SETTING: Along the continuum of care, including acute, early postacute, and long-term and community rehabilitation settings. PARTICIPANTS: Persons (N=9863) with various health conditions participated in primary studies. The number of respondents for whom the dependent variable data were available and used in this analysis was 9264. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: For regression analyses, self-reported general health was used as a dependent variable. The ICF categories from the functioning component and the EF component were used as independent variables for the development of the ICF Rehabilitation Set and the minimal set of EFs, respectively. RESULTS: Thirty ICF categories to be complemented with 12 EFs were identified as relevant to the identified ICF sets. The ICF Rehabilitation Set constitutes of 9 ICF categories from the component body functions and 21 from the component activities and participation. The minimal set of EFs contains 12 categories spanning all chapters of the EF component of the ICF. CONCLUSIONS: The identified sets proposed serve as minimal generic sets of aspects of functioning in clinical populations for reporting data within and across heath conditions, time, clinical settings including rehabilitation, and countries. These sets present a reference framework for harmonizing existing information on disability across general and clinical populations. PMID- 26827830 TI - Evaluation of Sexual Dysfunction in Men With Spinal Cord Injury Using the Male Sexual Quotient. AB - OBJECTIVE: To assess different aspects of sexual function in men with spinal cord injury (SCI) using the Male Sexual Quotient (MSQ), a newly developed tool to assess sexual function and satisfaction. DESIGN: Cross-sectional study. SETTING: Tertiary rehabilitation center. PARTICIPANTS: Patients (N=295) older than 18 years (mean age +/- SD, 40.7+/-14.5y) with SCI for more than 1 year (median time since SCI, 3.6y; range, 1.6-7.0y) were assessed from February to August 2012. Patients completed the MSQ questionnaire and the Sexual Health Inventory for Men (SHIM). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Performance in various domains of sexual function was evaluated using the MSQ and SHIM questionnaires. RESULTS: Erectile function, ejaculation, and orgasm were the most severely affected domains. The median MSQ score was 40 (range, 8-66), and the median SHIM score was 5 (range, 0-16). The diagnostic properties of the 2 instruments were similar in the discrimination of sexually active subjects. The area under the receiver operating characteristic curve was .950 (95% confidence interval [CI], .923-.979) for the MSQ and .942 (95% CI, .915-.968) for the SHIM. There was a strong correlation between the 2 instruments (r=.826; 95% CI, .802 .878). CONCLUSIONS: Different domains of sexual function are severely impaired in men with SCI, although their sexual interest remains high. The MSQ and SHIM scores strongly correlate, but the MSQ provides a more comprehensive assessment of sexual dysfunction in male patients with SCI. PMID- 26827831 TI - "Reps" Aren't Enough: Augmenting Functional Electrical Stimulation With Behavioral Supports Significantly Reduces Impairment in Moderately Impaired Stroke. AB - OBJECTIVE: To determine the impact of repetitive task-specific practice (RTP) integrating electrical stimulation and behavioral supports on upper extremity (UE) impairment, gross manual dexterity, and paretic UE amount and quality of use in chronic stroke survivors exhibiting moderate, stable UE deficits. DESIGN: Case series with 3-month follow-up. SETTING: Outpatient rehabilitation hospital. PARTICIPANTS: Persons (N=9) who experienced a stroke >12 months before enrollment and exhibiting chronic, moderate, stable UE impairment. INTERVENTIONS: After administering outcome measures, RTP was administered 3d/wk for 120 minutes with an electrical stimulation neuroprosthesis (60min in a supervised clinical setting; 60min at home) over 8 weeks. Behavioral supports (eg, behavior contract; weekly reviews of UE use) were provided during clinical sessions and integrated into home exercise sessions to increase paretic UE use and maximize carryover to subjects' community environments. MAIN OUTCOME MEASURES: The UE section of the Fugl-Meyer Impairment Scale, the Box and Block Test, and the Motor Activity Log. RESULTS: Subjects exhibited statistically significant (P<.01) increases on all measures at both time-point comparisons (ie, preintervention to postintervention; preintervention to 3mo postintervention). Subjects reported a new ability to perform valued activities they had not performed in months. CONCLUSIONS: Addition of behavioral supports to RTP augmented by electrical stimulation significantly increased paretic UE use and function. Significant motor changes were exhibited across ages and etiologies, and no other intervention was administered to this stable population, making it likely that results were not due to chance and suggests a larger trial is justified. PMID- 26827832 TI - Colonization pattern of C. jejuni isolates of human and avian origin and differences in the induction of immune responses in chicken. AB - Campylobacter jejuni (C. jejuni) is the most frequently reported bacterial food borne pathogen. Poultry is regarded to be the main reservoir for human campylobacteriosis. By some authors C. jejuni is considered as a commensal of the chicken gut, but clinical signs may be observed indicating host-pathogen interaction. Little is known about C. jejuni strain dependent differences in stimulation of the immune response in chicken. Therefore we investigated the colonization pattern as well as humoral and cell-mediated immune parameters in three-week old specific pathogen-free (SPF) layer-type (LT) chicken after inoculation with different human and avian derived C. jejuni isolates between three and 21dpi. In a subsequent experiment we investigated earlier time points and additionally compared commercial broilers with SPF-LT chicken to identify possible differences after inoculation of selected C. jejuni strains from prior experiments. No clinical symptoms were observed during the experiments. The colonization pattern did not correlate with the strain origin or magnitude of circulating C. jejuni specific antibodies. Only minor changes were observed in caecal T cell populations after C. jejuni inoculation compared to non-inoculated controls. Interestingly the mRNA expression of IL-6 and IFN-gamma was down regulated at some time points after inoculation suggesting a possible immunomodulatory effect of some C. jejuni strains in the gut. Furthermore, broilers were colonized to a higher extend and the local immune cell response was different compared to the SPF -LT birds indicating an influence of genotype on C. jejuni colonization pattern. Overall, our study demonstrates that the outcome of C. jejuni infection in chicken is influenced by genotype and partially by the C. jejuni isolate, leading to differences in the early immune response and thereafter the control of colonization and infection. PMID- 26827834 TI - Cancer immunology and canine malignant melanoma: A comparative review. AB - Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current "gold standard" treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics. PMID- 26827833 TI - Structural characterisation of Toll-like receptor 1 (TLR1) and Toll-like receptor 6 (TLR6) in elephant and harbor seals. AB - Pinnipeds are a diverse clade of semi-aquatic mammals, which act as key indicators of ecosystem health. Their transition from land to marine environments provides a complex microbial milieu, making them vulnerable to both aquatic and terrestrial pathogens, thereby contributing to pinniped population decline. Indeed, viral pathogens such as influenza A virus and phocine distemper virus (PDV) have been identified as the cause of several of these mass mortality events. Furthermore, bacterial infection with mammalian Brucella sp. and methicillin-resistant Staphylococcus aureus strains have also been observed in marine mammals, posing further risk to both co-habiting endangered species and public health. During these disease outbreaks, mortality rates have varied amongst different pinniped species. Analyses of innate immune receptors at the host-pathogen interface have previously identified variants which may drive these species-specific responses. Through a combination of both sequence- and structure based methods, this study characterises members of the Toll-like receptor (TLR) 1 superfamily from both harbour and elephant seals, identifying variations which will help us to understand these species-specific innate immune responses, potentially aiding the development of specific vaccine-adjuvants for these species. PMID- 26827835 TI - Development of recombinant BgP12 based enzyme linked immunosorbent assays for serodiagnosis of Babesia gibsoni infection in dogs. AB - Indirect ELISA and dot-ELISA using recombinant BgP12 (rBgP12) were developed for the diagnosis of Babesia gibsoni infected dogs. The complete open reading frame of BgP12 gene (378bp) was cloned in pET-32a(+) expression vector and expressed in Escherichia coli as a soluble thioredoxin (Trx) fusion protein. The purified rBgP12 was used for production of anti-rBgP12 rabbit serum, which recognized a native 12-kDa protein in B. gibsoni infected erythrocyte by Western blot analysis. To evaluate the potential of rBgP12 for the serodiagnosis of B. gibsoni, a panel of serum/plasma samples from dogs infected with B. gibsoni (n=13), uninfected sera (n=13) and sera from dogs infected with other haemoparasites viz., Babesia canis vogeli (n=3), Ehrlichia canis (n=3), Hepatozoon canis (n=1) and Dirofilaria immitis (n=1) were used in ELISA formats. In addition, the performance of rBgP12 based indirect ELISA and dot-ELISA were evaluated using 75 serum/plasma samples collected from suspected dogs, in respect to the nested PCR as reference test. The diagnostic sensitivities of indirect ELISA and dot-ELISA were 94.59% and 89.18%, respectively, while their specificities were 84.21% and 81.57%, respectively. Moreover, both the assays using rBgP12 showed no cross reaction with sera from dogs infected with other common haemoparasites indicating their high specificity. High kappa values of indirect ELISA and dot-ELISA indicated the potentials of these assays with substantial agreement at 95% confidence level. It is concluded that indirect ELISA and dot ELISA using rBgP12 might be used in large scale epidemiological surveys and clinical diagnosis of B. gibsoni infection in dogs. PMID- 26827836 TI - Immunologic progression of canine leishmaniosis following vertical transmission in United States dogs. AB - Canine leishmaniosis (CanL) is caused by Leishmania infantum, an obligate intracellular protozoan parasite, endemic in U.S. hunting dog populations. CanL has been found in dogs in 28 states and two Canadian provinces. Previous studies by our group, (Boggiatto et al., 2011), demonstrated that vertical transmission of Leishmania was the predominant means of transmission within U.S. dogs. Very little is known regarding how this alternative means of transmission, alters the long-term immunity and clinical presentation of leishmaniosis in dogs born to a positive bitch. This study follows the immunological progression of CanL in three pups after birth to an infected bitch. During the course of the study, these dogs were tested every six months over the course of six years. Both immunologic (IFN gamma, T cell proliferation, antibody production) and parasitological parameters (qPCR) of vertically-infected dogs were measured. Within the six years after birth to an L. infantum-infected, oligosymptomatic bitch, all dogs had at least one L. infantum PCR-positive test. Interestingly, despite living in the same location for their entire lives and being full siblings, these pups demonstrate three different disease progression patterns of L. infantum infection. One dog progressed to oligosymptomatic disease, maintaining a positive titer and had intermittent positive PCR results. One asymptomatic dog had positive serological titers and demonstrated a robust CD4(+) immune response to infection. The third dog had a negligible response to L. infantum antigen and was healthy. This work demonstrates the biologic variability associated with vertically-transmitted infection similar to the variety of presentations observed during vector-borne leishmaniosis. PMID- 26827837 TI - Effects of prepartum stocking density on innate and adaptive leukocyte responses and serum and hair cortisol concentrations. AB - Objectives were to evaluate the effects of prepartum stocking density on innate and adaptive leukocyte responses, serum cortisol and haptoglobin concentrations and hair cortisol concentration of Jersey cows. The cows (254 +/- 3d of gestation) were balanced for parity (nulliparous vs. parous) and previous lactation projected 305-d mature equivalent milk yield and assigned to one of two treatments: 80SD=80% stocking density (38 animals/48 headlocks) and 100SD=100% stocking density (48 animals/48 headlocks). Pens (n=4) were identical in size and design and each pen received each treatment a total of 2 times (4 replicates; 80SD: n=338; 100SD: n=418). A sub-group of cows (n=48/treatment per parity) was randomly selected on week 1 of each replicate from which blood was sampled weekly from d -14 to 14 (d 0=calving) to determine polymorphonuclear leukocyte (PMNL) phagocytosis, oxidative burst, and expression of CD18 and L-selectin, and hemogram. The same sub-group of cows was treated with chicken egg ovalbumin on d 21, -7, and 7 and had blood sampled weekly from d -21 to 21 for determination of serum IgG anti-ovalbumin concentration. Blood was sampled weekly from d -21 to 21 to determine glucose, cortisol, and haptoglobin concentrations in serum. Hair samples collected at enrollment and within 24h of calving were analyzed for cortisol concentration. The percentage of leukocytes classified as granulocyte and the granulocyte to the lymphocyte ratio were not affected by treatment. Treatment did not affect the percentage of PMNL positive for phagocytosis and oxidative burst or the intensity of phagocytosis and oxidative burst. Similarly, treatment did not affect the percentage of PMNL expressing CD18 and L-selectin or the intensity of expression of CD18 and L-selectin. Concentration of IgG anti ovalbumin was not affected by treatment. Serum concentrations of haptoglobin and cortisol were not affected by treatment. Similarly, hair cortisol concentration at calving was not affected by treatment. According to the current experiment, a target stocking density of 80% did not improve leukocyte responses compared with 100% target stocking density. PMID- 26827838 TI - Evidence of a pro-apoptotic effect of specific antibodies in a bovine macrophage model of infection with Mycobacterium avium subsp. paratuberculosis. AB - Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne's disease (JD), a chronic granulomatous enteritis in ruminants. Understanding the protective immune response following infection is crucial to improve the diagnosis and the development of vaccines against this disease. The goal of this work was to assess whether specific antibodies were able to modulate the macrophage response to MAP infection by evaluating apoptosis and TNF-alpha secretion in an in vitro model. Sera from healthy (n=2), MAP-infected (n=3) and lipoarabinomannan (LAM)-immunized (n=3) bovines were evaluated. LAM was chosen as immunogen due to its relevant role in mycobacterial pathogenesis. We demonstrated by two different techniques (Acridine Orange/Ethidium Bromide microscopy and Annexin V/7-Amino-Actinomycin D flow cytometry) that the immune sera from both, MAP-infected and LAM-immunized bovines, significantly increased macrophage apoptosis in infected cultures. Comparable levels of apoptosis were detected when MAP was pre-incubated with purified specific antibodies instead of whole serum. Furthermore, this effect was accompanied by a significantly higher secretion of TNF-alpha. These results strongly suggest that specific antibodies could limit the impact of MAP on the apoptosis of bovine cells. This work would contribute to elucidate the role of the specific antibody response in bovine JD and its prevention. PMID- 26827839 TI - The function of feline stimulator of interferon gene (STING) is evolutionarily conserved. AB - Stimulator of interferon gene (STING) mediates the induction of type I IFN responses. In this study, feline STING was cloned. Full-length STING contains 1134bp and encodes a 377 amino acid product that shares the highest similarity with bovine STING. STING is primarily expressed in the spleen, lungs and lymph nodes. An examination of its cellular localization indicated that STING is localized in the endoplasmic reticulum (ER) and contains two ER retention motifs, RPR and KKNF. Overexpressing STING induced the IFN response via the IRF3, NF kappaB and AP-1 pathways. Moreover, the C-terminus of STING was required for the activation of IRF3 and AP-1. Knockdown of STING impaired the IFN-beta response triggered by poly(dA:dT), poly(I:C) or SeV. Finally, STING activated the ISRE promoter and increased the expression of ISG15 and viperin. Collectively, our findings indicate that STING is involved in the regulation of the IFN-beta pathway in felines. PMID- 26827840 TI - Experimental evaluation of inactivated and live attenuated vaccines against Mycoplasma mycoides subsp. mycoides. AB - The current control method for contagious bovine pleuropneumonia (CBPP) in Africa is vaccination with a live, attenuated strain of Mycoplasma mycoides subsp. mycoides (Mmm). However, this method is not very efficient and often causes serious adverse reactions. Several studies have attempted to induce protection using inactivated mycoplasma, but with widely contradictory results. Therefore, we compared the protective capacity of the live T1/44 vaccine with two inactivated preparations of Mmm strain Afade, inoculated with an adjuvant. Protection was measured after a challenge with Afade. The protection levels were 31%, 80.8% and 74.1% for the formalin-inactivated, heat-inactivated and live attenuated preparations, respectively. These findings indicate that low doses of heat-inactivated Mmm can offer protection to a level similar to the current live attenuated (T1/44) vaccine formulation. PMID- 26827841 TI - Field application of immunoassays for the detection of Mycobacterium bovis infection in the African buffalo (Syncerus caffer). AB - The African buffalo (Syncerus caffer) is considered the most important maintenance host of bovine tuberculosis (BTB) in wildlife in Southern Africa. The diagnosis of Mycobacterium bovis infection in this species mostly relies on the single intradermal comparative tuberculin test (SICTT). As an alternative, the BOVIGAM(r) 1G, an interferon-gamma (IFN-gamma) release assay, is frequently used. The test performance of cell-mediated immunity (CMI-) and humoral immunity (HI-) based assays for the detection of M. bovis infections in buffaloes was compared to identify the test or test combination that provided the highest sensitivity in the study. Buffaloes were sampled during the annual BTB SICTT testing in the Hluhluwe-iMfolozi-Park (KwaZulu-Natal, South Africa) during June 2013. A total of 35 animals were subjected to the SICTT, 13 of these tested positive and one showed an inconclusive reaction. CMI-based assays (BOVIGAM(r) 1G (B1G) and BOVIGAM(r) 2G (B2G)) as well as a serological assay (IDEXX TB ELISA) were used to further investigate and compare immune responsiveness. Thirteen SICTT positive buffaloes and one inconclusive reactor were slaughtered and a post-mortem (PM) examination was conducted to confirm BTB. Lesions characteristic of BTB were found in 8/14 animals (57.1%). Test results of individual assays were compared with serial and parallel test interpretation and the sensitivity was calculated as a percentage of test positives out of the number of SICTT positive animals with granulomatous lesions (relative sensitivity). The B1G assay showed the highest individual sensitivity (100%; 8/8) followed by the B2G assay (75%; 6/8) and the IDEXX TB ELISA (37.5%; 3/8). Therefore, using in parallel interpretation, any combination with the B1G showed a sensitivity of 100% (8/8), whereas combinations with the B2G showed a 75% sensitivity (6/8). Out of the 21 SICTT negative animals, 7 animals showed responsiveness in the B2G or IDEXX TB ELISA. In conclusion, this study has shown that the BOVIGAM(r) IFN-gamma assay had the highest test performance. PMID- 26827842 TI - Evaluation of bovine thymic function by measurement of signal joint T-cell receptor excision circles. AB - A signal joint T-cell receptor excision circle (sjTREC) is a circular DNA produced by T-cell receptor alpha gene rearrangement in the thymus. Measurements of sjTREC values have been used to evaluate thymic function. We recently established a quantitative PCR (QPCR) assay of bovine sjTREC. In the present study, we used this QPCR assay to measure the sjTREC value in bovine peripheral blood mononuclear cells and we then evaluated the relationships between sjTREC values and peripheral blood T-cell number, growth stage, gender, and meteorological season. The sjTREC value was highest at the neonatal stage, and its value subsequently decreased with age. On the other hand, the peripheral T cell number increased with age. The sjTREC value in calves up to 50-days old was significantly higher for males than for females, suggesting that thymic function might differ by gender. In addition, the sjTREC value and the peripheral T-cell number were significantly higher in calves in the summer season than in calves in the winter season. These data suggest that bovine thymic function is highly variable and varies according to the growth stage, gender, and environmental factors such as air temperature or the UV index. PMID- 26827843 TI - NCR1+ cells appear early in GALT development of the ovine foetus and acquire a c kit+ phenotype towards the end of gestation. AB - The amount, distribution and phenotype of ovine NCR1+ cells were investigated during developing GALT from day 70 of gestation. Antibodies against CD3 and CD79 were used to identify the compartments of GALT, and the localization of NCR1+ cells were correlated within these structures. Markers CD34 and c-kit, in addition to Ki67, were used to investigate possible origin and the stage of development of the NCR1+ cells. NCR1+ cells were present as single cells in the subepithelial tissue as early as 70 days of gestation, and were predominantly present in the T cell rich IFAs and domes as these intestinal wall compartments developed. While NCR1+ cells proliferated more intensively at mid-gestation (70 104 days), the number of NCR1+ cells also expressing c-kit, increased at the end of gestation. In conclusion, NCR1+ cells appeared early in T cell areas of the gut and displayed a phenotype consistent with intermediate stages of cNK cells and/or a subpopulation of ILC22. PMID- 26827844 TI - Premature Ejaculation and Its Remedies in Medieval Persia. PMID- 26827845 TI - Centralization of Penile Cancer Management in the United States: A Combined Analysis of the American Board of Urology and National Cancer Data Base. AB - OBJECTIVE: To assess the potential benefit of centralization of care in penile cancer. Centralization of care in other disease processes standardizes treatment and improves outcomes. Because penile cancer is a rare malignancy with unchanged mortality rates over the last two decades, we hypothesize that there may be a benefit to centralization. METHODS: We identified surgeon, patient, and hospital characteristics captured by the National Cancer Data Base (1998-2012) and American Board of Urology case logs (2003-2013) for all penile cancer cases and procedures. Differences in patient demographics, stage of disease, referral patterns, and surgical quality indicators were assessed between academic and community hospitals. RESULTS: Using case logs to evaluate the distribution of penile cancer care, we found that only 4.1% of urologists performed a penile surgery and 1.5% performed a lymph node dissection (LND). Academic centers treated higher-stage cancers and saw more cases/year than community centers, suggesting informal centralization. Two guideline-based quality indicators demonstrated no difference in use of penile-sparing surgery but a higher likelihood of having an LND performed at an academic center (48.4% vs 26.6%). The total lymph node yield was significantly greater at academic centers (18.5 vs 12.5). Regression modeling demonstrated a 2.29 increased odds of having an LND at an academic center. CONCLUSION: Our data provide the first evidence for centralization of penile cancer in the US. At the time of diagnosis, equal number of patients is treated with penile-sparing surgery but there is greater use of LND and higher lymph node yield at academic centers. Ultimately, longer follow-up is necessary to determine if this improves survival of patients with penile cancer. PMID- 26827846 TI - The Effect of Urinary Incontinence on Health-related Quality of Life: Is It Similar in Men and Women? AB - OBJECTIVE: To compare the association between self-reported urinary incontinence (UI) and health-related quality of life (HRQoL) in men and women while taking chronic comorbidities into account, on the hypothesis that UI might negatively affect HRQoL differently in each sex. METHODS: In 2006, a total of 10,723 men (aged 57-67 years) and 3777 women (aged 52-67 years) participating in the GAZEL cohort (www.gazel.inserm.fr) completed a self-administered questionnaire including the Nottingham Health Profile to assess HRQoL. UI was defined as self reported involuntary loss of urine in the past 12 months. Adjusted logistic regression models were fitted to estimate the association between impaired HRQoL and UI, taking age, chronic conditions, and other confounders into account. For each QoL dimension, we compared the strength of the associations between UI and HRQoL between the sexes by tests of interaction. RESULTS: Women were more likely than men to report both UI (13.9% vs 2.7%) and impaired HRQoL. UI was associated with impaired HRQoL in both sexes, mainly in the dimensions of energy (OR = 3.17 in men [95% CI 2.49-4.04] and 2.11 in women [1.75-2.54]), social isolation (OR = 2.29 in men [1.74-3.02] and 1.75 in women [1.44-2.12]), and physical mobility (OR = 2.05 in men [1.62-2.60] and 2.27 in women [1.88-2.74]). There were no significant interactions between the sexes after adjustment. CONCLUSION: UI was associated negatively with HRQoL in both sexes, mostly in the dimensions of energy, social isolation, and physical mobility. The association was similar in men and women after we took age, sociodemographic characteristics, and chronic diseases into account. The cross-sectional design of the analysis prevents any conclusion that UI induced an impairment of HRQoL, and no causal relation can be inferred. PMID- 26827848 TI - Editorial Comment. PMID- 26827847 TI - Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. AB - Most patients who undergo surgical procedures experience acute postoperative pain, but evidence suggests that less than half report adequate postoperative pain relief. Many preoperative, intraoperative, and postoperative interventions and management strategies are available for reducing and managing postoperative pain. The American Pain Society, with input from the American Society of Anesthesiologists, commissioned an interdisciplinary expert panel to develop a clinical practice guideline to promote evidence-based, effective, and safer postoperative pain management in children and adults. The guideline was subsequently approved by the American Society for Regional Anesthesia. As part of the guideline development process, a systematic review was commissioned on various aspects related to various interventions and management strategies for postoperative pain. After a review of the evidence, the expert panel formulated recommendations that addressed various aspects of postoperative pain management, including preoperative education, perioperative pain management planning, use of different pharmacological and nonpharmacological modalities, organizational policies, and transition to outpatient care. The recommendations are based on the underlying premise that optimal management begins in the preoperative period with an assessment of the patient and development of a plan of care tailored to the individual and the surgical procedure involved. The panel found that evidence supports the use of multimodal regimens in many situations, although the exact components of effective multimodal care will vary depending on the patient, setting, and surgical procedure. Although these guidelines are based on a systematic review of the evidence on management of postoperative pain, the panel identified numerous research gaps. Of 32 recommendations, 4 were assessed as being supported by high-quality evidence, and 11 (in the areas of patient education and perioperative planning, patient assessment, organizational structures and policies, and transitioning to outpatient care) were made on the basis of low-quality evidence. PERSPECTIVE: This guideline, on the basis of a systematic review of the evidence on postoperative pain management, provides recommendations developed by a multidisciplinary expert panel. Safe and effective postoperative pain management should be on the basis of a plan of care tailored to the individual and the surgical procedure involved, and multimodal regimens are recommended in many situations. PMID- 26827849 TI - Characterization and expression analysis of Lc-Sox4 in large yellow croaker Larimichthys crocea. AB - The characterization and expression of Sox4 in large yellow croaker (Lc-Sox4) were studied in this paper. Lc-Sox4 contains a protein of 371 amino acids with a conserved high mobility group box. Quantitative real-time PCR displayed that the expression of Lc-Sox4 had tissue and gender specificity existing in brain, gonad, heart, intestine, and head kidney with male>female, in eye with female>male. During embryogenesis, Lc-Sox4 was expressed highest in one-day-post-hatching stage, next in formation-of-eye-lens stage. The expression pattern of Lc-Sox4 was different from that of Lc-Sox11a. The expression of Lc-Sox4 was significantly lower than that of Lc-Sox11a in the all tested tissues and embryonic stages except in heart, spleen, mutiple-cell, formation-of-eye-lens, and one-day-post hatching stages (with Lc-Sox4 higher than Lc-Sox11a). There was overlapping expression between Lc-Sox4 and Lc-Sox11a in brain, gill, female eye, testis, formation-of-eye-lens stage and one-day post hatching stage. The whole mount in situ hybridization results indicated that Lc-Sox4 was expressed at all embryonic stages except 2-cell stage. The positive signals were mainly distributed in the central nervous system and notochord at one-day-post-hatching stage. In short, we first identified and analyzed the temporal and spatial expression patterns of Lc Sox4 to elucidate its important influence on the development of nervous system, visual system and heart. We also detected the overlapping expression between Lc Sox4 and Lc-Sox11a which may reveal the functional redundancy of them. These data would shed light on the molecular mechanism of development in large yellow croaker. PMID- 26827851 TI - Ontogeny of osmoregulation in the Pacific blue shrimp, Litopenaeus stylirostris (Decapoda, Penaeidae): Deciphering the role of the Na(+)/K(+)-ATPase. AB - The role of the main ion transporting enzyme Na+/K+-ATPase in osmoregulation processes was investigated in Litopenaeus stylirostris. The development and localization of the osmoregulation sites were studied during ontogenesis by immunodetection of Na(+)K(+)-ATPase using monoclonal antibodies and transmission electron microscopy (TEM). Osmoregulation sites were identified as the pleurae and branchiostegites in the zoeae and mysis stages. In the subsequent post metamorphic stages the osmoregulatory function was mainly located in the epipodites and branchiostegites and osmotic regulation was later detected in the gills. The presence of ionocytes and microvilli in these tissues confirmed their role in ionic processes. The complete open reading frame of the mRNA coding for the alpha-subunit of Na+K+-ATPase was characterized in L. stylirostris. The resulting 3092-bp cDNA (LsNKA) encodes a putative 1011-amino-acid protein with a predicted molecular mass of 112.3kDa. The inferred amino acid sequence revealed that the putative protein possesses the main structural characteristics of the Na+K+-ATPase alpha-subunits. Quantitative RT-PCR analyses indicated that LsNKA transcripts did not significantly vary between the different developmental stages. The number of transcripts was about 2.5-fold higher in the epipodites and gills than in any other tissues tested in juveniles. A reverse genetic approach was finally implemented to study the role of LsNKA in vivo. Knockdown of LsNKA expression by gene-specific dsRNA injection led to an increase of shrimp mortality following an abrupt salinity change compared to control animals. These data strongly suggest that LsNKA plays an important role in osmoregulation when the shrimp are challenged by changing salinities. PMID- 26827852 TI - In vitro growth inhibitory efficacy of some target specific novel drug molecules against Theileria equi. AB - The in vitro growth inhibitory efficacies of five drug molecules against Theileria equi were evaluated in in vitro cultured parasites. A continuous microaerophilic stationary-phase culture (MASP) system was established for propagation of T. equi parasites. This in vitro culture system was used to assess the growth inhibitory effect of harmaline hydrochloride dihydrate (HHD), hexadecyltrimethylammonium bromide (HDTAB), hesparidin methyl chalcone (HMC), andrographolide and imidocarb dipropionate against T. equi. The 50% inhibitory concentration value of HHD, HDTAB, HMC, and imidocarb dipropionate for T. equi growth were 17.42 MUM, 14.00 MUM, 246.34 MUM and 0.279 MUM (equivalent to 0.139 MUg/ml), respectively (P<0.05). The andrographolide was not effective in inhibiting in vitro growth of T. equi in the present study. Furthermore, the in vitro cytotoxicity of these five drugs was evaluated on horse PBMC. At 2000 MUM concentration of HHD, HDTAB, HMC, andrographolide and imidocarb dipropionate were 8.34, 46.44, 58.53, 31.06, 15.14% cytotoxic on PBMC, respectively. Out of our four tested drug molecules, HHD was having low IC50 value along with least cytotoxicity, as compared to reference drug imidocarb dipropionate. The difference in IC50 value of HDTAB and HHD was significant, but HDTAB was moderately more cytotoxic on PBMC cell lines. HHD and HDTAB are selective inhibitor for heat shock protein 90 (Hsp90) and choline kinase pathway. It can be concluded that HHD and HDTAB are potential drug molecules against T. equi parasite by acting on Hsp90 and choline kinase pathway. PMID- 26827850 TI - Myostatin inhibitory region of fish (Paralichthys olivaceus) myostatin-1 propeptide. AB - Myostatin (MSTN) is a potent negative regulator of skeletal muscle growth, and its activity is suppressed by MSTN propeptide (MSTNpro), the N-terminal part of MSTN precursor cleaved during post-translational MSTN processing. The current study examined which region of flatfish (Paralichthys olivaceus) MSTN-1 propeptide (MSTN1pro) is critical for MSTN inhibition. Six different truncated forms of MSTN1pro containing N-terminal maltose binding protein (MBP) as a fusion partner were expressed in Escherichia coli, and partially purified by an affinity chromatography for MSTN-inhibitory activity examination. Peptides covering different regions of flatfish MSTN1pro were also synthesized for MSTN-inhibitory activity examination. A MBP-fused MSTN1pro region consisting of residues 45-100 had the same MSTN-inhibitory potency as the full sequence flatfish MSTN1pro (residues 23-265), indicating that the region of flatfish MSTN1pro consisting of residues 45-100 is sufficient to maintain the full MSTN-inhibitory capacity. A MBP-fused MSTN1pro region consisting of residues 45-80 (Pro45-80) also showed MSTN-inhibitory activity with a lower potency, and the Pro45-80 demonstrated its MSTN binding capacity in a pull-down assay, indicating that the MSTN-inhibitory capacity of Pro45-80 is due to its binding to MSTN. Flatfish MSTN1pro synthetic peptides covering residues 45-65, 45-70, and 45-80 demonstrated MSTN-inhibitory activities, but not the synthetic peptide covering residues 45-54, indicating that residues 45-65 of flatfish MSTN1pro are essential for MSTN inhibition. In conclusion, current study show that like the mammalian MSTNpro, the MSTN inhibitory region of flatfish MSTN1pro resides near its N-terminus, and imply that smaller sizes of MSTNpro can be effectively used in various applications designed for MSTN inhibition. PMID- 26827853 TI - Assessing the risk of bovine fasciolosis using linear regression analysis for the state of Rio Grande do Sul, Brazil. AB - Fasciola hepatica is the causative agent of fasciolosis, a disease that triggers a chronic inflammatory process in the liver affecting mainly ruminants and other animals including humans. In Brazil, F. hepatica occurs in larger numbers in the most Southern state of Rio Grande do Sul. The objective of this study was to estimate areas at risk using an eight-year (2002-2010) time series of climatic and environmental variables that best relate to the disease using a linear regression method to municipalities in the state of Rio Grande do Sul. The positivity index of the disease, which is the rate of infected animal per slaughtered animal, was divided into three risk classes: low, medium and high. The accuracy of the known sample classification on the confusion matrix for the low, medium and high rates produced by the estimated model presented values between 39 and 88% depending of the year. The regression analysis showed the importance of the time-based data for the construction of the model, considering the two variables of the previous year of the event (positivity index and maximum temperature). The generated data is important for epidemiological and parasite control studies mainly because F. hepatica is an infection that can last from months to years. PMID- 26827854 TI - Molecular and morphologic characterization of Sarcocystis felis (Apicomplexa: Sarcocystidae) in South American wild felids from Brazil. AB - Wild felids are thought to share parasites with domestic cats. However, little is known of the coccidian parasites of wild felids. We investigated the presence of Sarcocystis spp. in tissues of 6 species of 90 Neotropical small felids killed in road accidents in the state of Rio Grande do Sul, Brazil by using microscopic and molecular techniques. Formalin-fixed tissues from 28 felids were examined, and Sarcocystis felis-like sarcocysts were detected in 4 wild cats (2 Puma yagouaroundi and 2 Leopardus guttulus). By transmission electron microscopy, sarcocysts from a P. yagouaroundi were identical to S. felis from domestic cats in the USA. Direct sequencing of PCR amplicons resulted the unambiguous sequences of the ITS-1 region from 18 of the 31 PCR positive wild cats; 5 sequences from each P. yagouaroundi, and Leopardus geoffroyi, 4 sequences from L. guttulus, and 2 sequences from each Leopardus wiedii, and Leopardus colocolo. Sequences analysis of ITS-1 region revealed the highest identiy (97-99%) with that of previously describe isolates of S. felis from domestic cats in the USA and identified them as S. felis. Tissues of 1 Leopardus pardalis tested by PCR and histology were negative. The phylogenetic relationship indicated that S. felis is quite different to species which employ opossums as their definitive host. This is the first report of S. felis infection in small wild felids from Brazil. PMID- 26827855 TI - Effect of vacuum packing and temperature on survival and hatching of strongyle eggs in faecal samples. AB - Strongyle eggs of helminths of livestock usually hatch within a few hours or days after deposition with faeces. This poses a problem when faecal sampling is performed in the field. As oxygen is needed for embryonic development, it is recommended to reduce air supply during transport and refrigerate. The present study therefore investigated the combined effect of vacuum packing and temperature on survival of strongyle eggs and their subsequent ability to hatch and develop into L3. Fresh faecal samples were collected from calves infected with Cooperia oncophora, pigs infected with Oesophagostomum dentatum, and horses infected with Strongylus vulgaris and cyathostomins. The samples were allocated into four treatments: vacuum packing and storage at 5 degrees C or 20 degrees C (5 V and 20 V); normal packing in plastic gloves closed with a loose knot and storage at 5 degrees C or 20 degrees C (5 N and 20 N). The number of eggs per gram faeces (EPG) was estimated every fourth day until day 28 post set up (p.s.) by a concentration McMaster-method. Larval cultures were prepared on day 0, 12 and 28 p.s. and the larval yield determined. For C. oncophora, the EPG was significantly higher in vacuum packed samples after 28 days as compared to normal storage, regardless of temperature. However, O. dentatum EPG was significantly higher in samples kept at 5 degrees C as compared to 20 degrees C, irrespective of packing. For the horse strongyles, vacuum packed samples at 5 degrees C had a significantly higher EPG compared to the other treatments after 28 days. The highest larval yield of O. dentatum and horse strongyles were obtained from fresh faecal samples, however, if storage is necessary prior to setting up larval cultures O. dentatum should be kept at room temperature (aerobic or anaerobic). However, horse strongyle coprocultures should ideally be set up on the day of collection to ensure maximum yield. Eggs of C. oncophora should be kept vacuum packed at room temperature for the highest larval yield. PMID- 26827856 TI - Experimental infection of calves with Haemonchus placei and Haemonchus contortus: Assessment of parasitological parameters. AB - The present study evaluated the viability and possible effects of Haemonchus contortus infections in experimentally prime infected calves, comparing them to infections by Haemonchus placei. Ten male Holstein newborns were used. All calves were individually weighed for subsequent group formation, in which two animals were kept as a control group, inoculated with water (GI); four animals were inoculated with 10,000 third stage (L3) Haemonchus contortus larvae (GII); and the remaining four calves were inoculated with 10,000 third stage (L3) H. placei larvae (GIII). All experimental animals were necropsied on the 42nd day after inoculation. Based on results obtained by the present study, it can be concluded that bovine calves were susceptible to infections by both Haemonchus species (placei and contortus). H. contortus presented an inferior pre-patent period when compared to H. placei. No significant difference (P>0.05) was observed between Haemonchus burdens recovered from both infected groups (GII and GIII). Moreover, H. contortus females maintained an egg production rate similar to H. placei females in young animals, which can contribute to pasture contamination by both Haemonchus species. This could possibly lead to negative reflexes on helminth control based on a mixed pasture with bovines and ovines, especially when it involves younglings. PMID- 26827857 TI - Efficacy of afoxolaner plus milbemycin oxime chewable tablets against naturally acquired intestinal nematodes in dogs. AB - The efficacy of oral afoxolaner plus milbemycin oxime combination chewable tablets (NexGard Spectra, Merial) against naturally acquired intestinal nematode infections in dogs was evaluated in six negative control, blinded studies including a total of 114 dogs. Dogs were selected based on a pre-treatment fecal examination indicating patent infections with hookworms (two studies), Toxocara or Toxascaris ascarids (one study each) or Trichuris whipworms (two studies). In each study, dogs were assigned to blocks of two animals each, based on decreasing pre-treatment body weight and were randomly allocated to one of two groups consisting of eight, nine or 10 dogs: untreated (control) or treated with the combination chewable tablet formulation. Chewable tablets were combined to provide doses of actives as close as possible to the minimum effective dose of afoxolaner and milbemycin oxime, i.e., 2.5 mg/kg body weight and 0.5 mg/kg body weight, respectively, once on Day 0. For parasite recovery and count, dogs were euthanized humanely and necropsied seven or eight days after treatment. A single treatment with afoxolaner plus milbemycin oxime chewable tablets provided 94.8% and 90.9% efficacy against adult Ancylostoma braziliense and A. caninum, respectively, 97.8% and 99.4% efficacy against adult Toxocara canis and Toxascaris leonina, respectively, and >=98.3% efficacy against adult Trichuris vulpis. Compared to untreated controls, nematode counts of the treated dogs were significantly reduced (F-test; p<0.002). In addition, analysis of the pooled data across studies revealed that treatment with afoxolaner plus milbemycin oxime chewable tablets reduced adult Uncinaria stenocephala burdens by 74.9% (p=0.002). All dogs tolerated the treatment well based on clinical observations post treatment and daily clinical observations. No adverse experiences or other clinical problems related to the treatment were observed throughout the studies. The results of this series of controlled studies demonstrated high efficacy and excellent acceptability and safety of the afoxolaner plus milbemycin oxime chewable tablets when administered for treatment of a broad range of canine intestinal nematode infections. PMID- 26827858 TI - The incidence and species composition of Gasterophilus (Diptera, Gasterophilidae) causing equine myiasis in northern Xinjiang, China. AB - A survey was conducted on the detection of the larval Gasterophilus species in 90 equines via necropsy or after administering oral ivermectin in Xinjian, China, from 2008 to 2013. All 90 (100%) equines were infested by larval Gasterophilus, and 3723second instar larvae (L2) and 63,778 third instar larvae (L3) were collected from faecal samples and the digestive tract, a ratio of L2:L3=1:17. Over 84.45% of the animals contained <=1500 larvae and 7.78% had >2000 larvae. The highest totals of L2 and L 3 larvae in any one animal were 1208 in Mongolian wild ass (Equus hemionus hemionus), 2491 in Przewalski's horse (Equus ferus przewalskii), and 1785 in the domestic horse (Equus ferus caballus). Six species of Gasterophilus were identified, with the following proportions of overall parasite abundance: Gasterophilus pecorum 88.94%, Gasterophilus nigricornis 4.94%, Gasterophilus nasalis 3.93%, Gasterophilus haemorrhoidalis 1.91%, Gasterophilus intestinalis 0.19%, and Gasterophilus inermis 0.087%. A majority of equines (n=32, 35.57%) was infested with five Gasterophilus species, while 29 animals (32.22%) harboured four species, 13 animals (14.44%) had six, 12 animals (13.33%) had three, three (3.33%) had two, and one (1.11%) had only one species. The percentage of Przewalski's horses infested was higher than local domestic horse or Mongolian wild ass. PMID- 26827859 TI - Detection and molecular characterisation of Cryptosporidium parvum in British European hedgehogs (Erinaceus europaeus). AB - Surveillance was conducted for the occurrence of protozoan parasites of the genus Cryptosporidium in European hedgehogs (Erinaceus europaeus) in Great Britain. In total, 108 voided faecal samples were collected from hedgehogs newly admitted to eight wildlife casualty treatment and rehabilitation centres. Terminal large intestinal (LI) contents from three hedgehog carcasses were also analysed. Information on host and location variables, including faecal appearance, body weight, and apparent health status, was compiled. Polymerase Chain Reaction (PCR) targeting the 18S ribosomal RNA gene, confirmed by sequencing, revealed an 8% (9/111) occurrence of Cryptosporidium parvum in faeces or LI contents, with no significant association between the host or location variables and infection. Archived small intestinal (SI) tissue from a hedgehog with histological evidence of cryptosporidiosis was also positive for C. parvum by PCR and sequence analysis of the 18S rRNA gene. No other Cryptosporidium species were detected. PCR and sequencing of the glycoprotein 60 gene identified three known zoonotic C. parvum subtypes not previously found in hedgehogs: IIdA17G1 (n=4), IIdA19G1 (n=1) and IIdA24G1 (n=1). These subtypes are also known to infect livestock. Another faecal sample contained C. parvum IIcA5G3j which has been found previously in hedgehogs, and for which there is one published report in a human, but is not known to affect livestock. The presence of zoonotic subtypes of C. parvum in British hedgehogs highlights a potential public health concern. Further research is needed to better understand the epidemiology and potential impacts of Cryptosporidium infection in hedgehogs. PMID- 26827860 TI - Lung parasites of the genus Metastrongylus Molin, 1861 (Nematoda: Metastrongilidae) in wild boar (Sus scrofa L., 1758) in Central-Italy: An eco epidemiological study. AB - The respiratory tracts of 57 wild boars (Sus scrofa L. 1758) hunted in central Italy during the 2011/2012 hunting season were examined to detect the presence of lung worms. Fifty-five out of 57 animals (96,5%) were positive. Five species of Metastrongylus were detected and their prevalence was as follows: Metastrongylus asymmetricus Noda, 1973 (91.2%), Metastrongylus confusus Jansen, 1964 and Metastrongylus salmi Gedoelst, 1923 (87.7%), Metastrongylus apri Gmelin, 1790 (80.7%), Metastrongylus pudendotectus Vostokov, 1905 (70.2%). In most cases multi species infection was observed. The highest parasite load was found in young animals (<1 year old). The Metastrongylus genus sex ratio (M/F) had a range from 1:4.8 to 1:1.5 in favor of females. The Simpson and Shannon-Wiener indices showed a moderate uniformity in parasite community composition. The Fager index highlighted a high degree of affinity among all pairs of selected parasites. The whole parasite population showed an aggregate distribution. Our findings confirm that these parasites are widespread in the wild boar population. The establishment of outdoor domestic pig farming in the same area of the game preserve could pose the risk of infection to domestic animals. Further studies will be needed to understand the factors involved in the presence and prevalence of the intermediate host as well as the population dynamics of Metastrongylus spp. PMID- 26827861 TI - In vitro susceptibility of ten Haemonchus contortus isolates from different geographical origins towards acetone:water extracts of two tannin rich plants. AB - The aim of the study was to examine the variation in the in vitro susceptibility of ten Haemonchus contortus isolates from different geographical origins using respective egg hatch assays (EHA) with acetone:water extracts of two tannin containing plants, chimay (Acacia pennatula) and sainfoin (Onobrychis viciifolia). Fresh eggs were incubated in PBS with different concentrations of each extract (0, 600, 1200, 2400, 3600, 5000 and 8000 MUg/ml PBS). Additional concentrations were tested for O. viciifolia (75, 100, 200 and 400 MUg/ml PBS). Effective concentrations 50% (EC50), with the corresponding 95% confidence interval (95% CI), were calculated for every isolate with both extracts. Moreover, a resistance ratio (RR) was calculated to compare the isolates, using the most susceptible isolate for each extract as the respective reference. A second set of incubations were made using polyvinylpolypyrrolidone (PVPP) (0, 5000 MUg/ml, 5000 MUg/ml+PVPP) to determine the influence of polyphenols on the AH effect. The proportion of morulated eggs, eggs with L1 larvae failing eclosion (%LFE), and emerged larvae were estimated at different extract concentrations. Data of each isolate was used to calculate the effective concentration 50% (EC50) for each extract. The EC50 of each isolate was used to determine resistance ratio (RR) for the different isolates. For the 2 extracts, a susceptibility variation in egg hatching was observed for the different H. contortus isolates. The EC50 values for A. pennatula ranged from 2203 to 14106 MUg (RR from 2.01 to 6.40). The O. viciifolia extract showed higher variability with EC50 values ranging from 104 to 4783 MUg (RR from 3.66 to 45.74). The main AH effects of the two extracts tested on the ten isolates consisted in blocking the emergence of L1 larvae (higher% LFE). Additional observations on emerged larvae showed that extract exposure caused alterations in the internal structure, separating the cuticle from the pharynx, bulb and intestinal cells. The use of PVPP revealed that (a) condensed tannins were not the sole plant secondary metabolites responsible for the AH effects, and (b) different H. contortus isolates showed variability in the role of tannins either on the ovicidal effect or the %LFE. PMID- 26827862 TI - First report of Echinococcus granulosus (genotype G6) in a dog in Bamako, Mali. AB - Cystic echinococcosis is one of the most widespread and important helminthic zoonoses, caused by the larval stage of Echinococcus granulosus sensu lato. However, to date there is little information about the disease in West Africa. Faecal and fur samples from 193 dogs, the main final hosts, were collected in 2010 and 2011 in Bamako, Mali. Taeniid eggs were found microscopically in 28/118 (24%) and 80/223 (36%) faecal and fur samples, respectively. One faecal and one fur sample from the same dog were positive for E. granulosus s. l. DNA. In the remaining 27 faecal (96%) and 77 fur samples (96%) only Taenia DNA was detected. Three microscopically positive fur samples were negative by PCR. Sequence analysis of part of the NADH dehydrogenase subunit 1 gene identified the parasite as E. granulosus (genotype G6; Echinococcus canadensis). This is the first study to focus on the final host of E. granulosus s. l. in Mali and the first report of E. canadensis in Mali. PMID- 26827863 TI - Survey of cattle tick, Riphicephalus (Boophilus) microplus, resistance to amitraz and deltamethrin in New Caledonia. AB - The evolution of tick resistance to acaricides in New Caledonia was followed in two ways: through two large scale surveys in 1998 and 2014 and through the routine analysis of samples of ticks with suspected resistance. The results of the two approaches were qualitatively similar though analysis of ticks with suspected resistance gave higher frequencies of resistance, as expected of a biased sample. Resistance tests using a larval packet test have been conducted since 1993 for deltamethrin and 2003 for amitraz. Deltamethrin was used in country-wide control from 1986 to 2003 and amitraz since 1996. This study analyzed the variation of resistance parameters such as lethal concentration 50 (LC50) and the resistance factor over 21 years for deltamethrin and LC99 over 11 years for amitraz. There was an increase in deltamethrin's annual mean LC50 from 1993 to 2004 when it reached 2.9 g/l and then a progressive decrease, reaching a level consistently below 1g/l since 2007. Even though breeders stopped using deltamethrin in New Caledonia in 2003, the percentage of susceptible strains has remained below 30% since 1998. Amitraz's LC99 mean increased significantly from 0.31 g/l in 2003 to 2.96 g/l in 2014. Whereas all tested strains in 2003 were susceptible, only 40% of strains tested at the request of farmers were susceptible in 2014. The recent territory-wide survey showed that 76.7% of strains are still susceptible. This study established that resistance to amitraz has developed slowly in New Caledonia. A reversion phenomenon may have occurred concerning deltamethrin resistance, visible through the decrease of LC50 mean and the decreased proportion of very resistant strains; however the proportion of susceptible strains remains at a low level and there is anecdotal evidence that high resistance can re-emerge rapidly. PMID- 26827864 TI - Giardia duodenalis genotypes in domestic and wild animals from Romania identified by PCR-RFLP targeting the gdh gene. AB - Sixty Giardia duodenalis isolates from domestic (n=49) and wild (n=11) animals (dogs, cats, deers, wolves, raccoon dog and muskrat) were analysed by PCR-RFLP at glutamate dehydrogenase locus (gdh). The isolates were obtained from positive feces samples for Giardia cysts analysed by flotation technique with saturated sodium chloride solution (specific gravity 1.28). Three G. duodenalis genotypes were identified: C (10/60; 16.7%); D (42/60; 70.0%); and E (7/60; 11.7%). In dogs all three genotypes were found, with the following prevalences: 76.9% genotype D (30/39); 23.1% C (9/39); 2.6% genotype E (1/39). One dog was co-infected with C and D genotypes. In cats we identified only G. duodenalis genotype D. Wolves and raccoon dog harbored infection with G. duodenalis genotype D, deers with E type and muskrat C type. This is the first study regarding genotyping of G. duodenalis in cats and wild animals from Romania. To the best of our knowledge, this is the first report of assemblages E in roe deers; assemblage C in wolves and muskrat; and assemblage D in raccoon dog. PMID- 26827865 TI - Use of fluorescent lectin binding to distinguish eggs of gastrointestinal nematode parasites of sheep. AB - The binding of a panel of 19 lectins to carbohydrates on the eggs of economically important nematode parasites of sheep has been assessed as the basis of a rapid test to distinguish parasite eggs, at least at the genus level. A total of six lectins can be used to identify eggs of six nematode parasites: peanut agglutinin (PNA) for Haemonchus contortus; Lens culinaris agglutinin (LCA) for Teladorsagia sp; Aleuria aurantia agglutinin (AAL) for Trichostrongylus sp; Psophocarpus tetragonolobus-II (PTLII) for Nematodirus sp; Lotus tetragonolobus lectin (LTL) for Cooperia sp and wheat germ agglutinin (WGA) for Chabertia ovina. For WGA, LCA and LTL, weak binding was also observed to H. contortus and Teladorsagia sp, Trichostrongylus sp and C. ovina eggs, respectively. Nematode eggs in two faecal samples were identically identified by both lectin binding and PCR, except for PCR identification of the eggs of Nematodirus sp, as these did not lyse. Lectins bound best to H. contortus eggs extracted from fresh faecal samples or after storage at room temperature or 4 degrees C for up to 24 h, but eggs stored at 20 degrees C or -80 degrees C did not bind PNA. PMID- 26827866 TI - An effective in vitro and in vivo antileishmanial activity and mechanism of action of 8-hydroxyquinoline against Leishmania species causing visceral and tegumentary leishmaniasis. AB - The development of new therapeutic strategies to treat leishmaniasis has become a priority. In the present study, the antileishmanial activity of 8 hydroxyquinoline (8-HQN) was investigated against in vitro promastigotes and in vivo intra-macrophage amastigotes of three Leishmania species: Leishmania amazonensis, Leishmania infantum and Leishmania braziliensis. Studies were performed to establish the 50% Leishmania inhibitory concentration (IC50) of 8 HQN, as well as its 50% cytotoxic concentration (CC50) on murine macrophages and in human red blood cells. The inhibition of macrophages infection was also evaluated using parasites that were pre-treated with 8-HQN. The effects of this compound on nitric oxide (NO) production and in the mitochondrial membrane potential were also evaluated. Finally, the therapeutic efficacy of 8-HQN was assessed in a known murine model, L. amazonensis-chronically infected BALB/c mice. Our results showed that 8-HQN was effective against promastigote and amastigote stages of all tested Leishmania species, presenting a selectivity index of 328.0, 62.0 and 47.0 for L. amazonensis, L. infantum and L. braziliensis, respectively. It was effective in treating infected macrophages, as well as in preventing the infection of these cells using pre-treated parasites. In addition, 8-HQN caused an alteration in the mitochondrial membrane potential of the parasites. When administered at 10mg/kg body weight/day by subcutaneous route, this product was effective in reducing the lesion diameter, as well as the parasite load in evaluated tissues and organs of infected animals. The results showed the in vitro and in vivo efficacy of 8-HQN against three different Leishmania species causing tegumentary and/or visceral leishmaniasis, and it could well be used for future therapeutic optimization studies to treat leishmaniasis. PMID- 26827867 TI - Anti-parasitic effects of Leptomycin B isolated from Streptomyces sp. CJK17 on marine fish ciliate Cryptocaryon irritans. AB - The present study was conducted aiming to evaluate the in vitro and in vivo anti parasitic efficacy of an isolated compound against the ciliate Cryptocaryon irritans. The compound was previously isolated from fermentation products of Streptomyces sp. CJK17 and designated as SFrD. Toxicity of the compound SFrD against the fish hosts (Larimichthys crocea) was also tested and its chemical structure was elucidated. The obtained results showed that the compound has potent anti-parasitic efficacy with the 10 min-, 1 h-, 2 h-, 3 h- and 4 h-LC50 (95% Confidence Intervals) of 6.8 (6.5-7.1), 3.9 (2.8-5.0), 3.3 (2.6-4.0), 2.7 (2.3-3.1) and 2.5 (2.2-2.8) mg L(-1) against theronts of C. irritans and the 6h LC50 (95% CI) of 3.0 (2.8-3.2) mg L(-1) against the tomonts, respectively. Exposure of the compound SFrD remarkably reduced the mortality of fish infected with C. Irritans, from 100% in the control group to 61.7% and 38.3% in groups of 3.1 mg L(-1) and 6.3 mg L(-1), respectively. In the test of exposing fish to 40 mg L(-1) compound SFrD for 24h, no visible effects were observed affecting the normal behavior or any macroscopic changes. By spectrum analysis (EI-MS, (1)H NMR and (13)C NMR), the compound SFrD was identified as Leptomycin B. This study firstly demonstrated that Leptomycin B has potent anti-parasitic efficacy against ciliates in cultured marine fish. PMID- 26827868 TI - Plasma disposition, milk excretion and parasitological efficacy of mebendazole in donkeys naturally infected by Cyathostominae. AB - Mebendazole (MBZ) has been licensed for use in horses and donkeys, however there are no data available in the literature regarding its pharmacokinetic disposition and efficacy in donkeys. This study was designed to determine the plasma disposition, milk excretion and anthelmintic efficacy of MBZ in donkeys naturally infected by Cyathostominae. The animals were allocated to three groups, each of six donkeys. One group was untreated control (C-group) and the others were treated using a paste formulation of MBZ administered per os at the manufacturer's recommended horse dosage of 10 mg/kg body weight (MBZ 1) and at the double horse dosage 20 mg/kg body weight (MBZ 2). Blood and milk samples were collected at various times between 1h and 120 h post treatment and analyzed by high performance liquid chromatography with photodiode array detector. Individual FECs (Faecal Egg Counts) were performed on each animal before the treatment (day 3) and weekly from day 7 until day 56 post treatment using a modified McMaster technique. The plasma concentrations and systemic exposure of MBZ in donkeys were relatively lower compared with the other methylcarbamate benzimidazoles. Dose dependent plasma dispositions of MBZ were observed at the increased dosage (10 mg/kg vs 20 mg/kg) in donkeys. MBZ was not detected in any milk samples at a dosage of 10 mg/kg. However, the parent drug reached 0.01 MUg/ml peak milk concentration at 10.66 h and AUCmilk/AUCplasma value was 0.18 +/- 0.02 at a dosage of 20 mg/kg bodyweight. This study indicated that per os administration of MBZ has a minimal disposition rate into the milk and may be used in lactating donkeys with zero milk-withdrawal period. The results of FECRT for both MBZ dosages were efficient (>95% efficacy) until day 28. This trial demonstrates that MBZ oral paste at horse dosage (10 mg/kg B.W.) was effective and safety for the treatment of Cyathostominae in donkeys. Therefore, similar dosage regimens of MBZ could be used for horses and donkeys. PMID- 26827869 TI - Molecular and serological detection of Babesia bovis- and Babesia bigemina infection in bovines and water buffaloes raised jointly in an endemic field. AB - Babesia bovis and Babesia bigemina are causative agents of bovine babesiosis, a tick-borne disease of cattle in tropical and subtropical regions. Babesia spp. infection adversely affects cattle health and can be fatal resulting in considerable economic loss worldwide. Under endemic stability conditions, herds contain high numbers of chronically infected, asymptomatic carrier animals, in which no parasitemia is detected by microscopic blood smear examination. In addition to bovines, also water buffaloes are infected by both Babesia spp. commonly leading to a subclinical infection. The infection rate (by nPCR) and herd exposure (by IFAT) of bovines and water buffaloes reared under similar field conditions in an area of endemic stability were determined and compared. In order to optimize direct parasite detection, highly sensitive nPCR assays were developed and applied, allowing the detection of as little as 0.1 fg DNA of each Babesia pathogen. Significantly lower percentages (p<0.001) of seropositive water buffaloes compared to bovines were observed for B. bovis (71.4% vs. 98%) and B. bigemina (85% vs. 100%). Interestingly, in comparison, differences noticed between water buffaloes and bovines were considerably larger with direct parasite detection by nPCR (16.2% vs. 82.3% and 24% vs. 94.1% for B. bovis and B. bigemina, respectively). As expected, bovines subjected to monthly acaricide applications exhibited a significant lower infection rate as determined by nPCR than bovines not subjected to these measures (B. bovis 33.3% vs. 90.7%, p<0.001; B. bigemina 80% vs. 96.5%, p<0.001, for treated vs. untreated animals). Interestingly no differences between these groups were observed with respect to seropositivity, suggesting similar rates of parasite exposure (B. bovis 100% vs. 97.7%, p<0.001; B. bigemina 100% vs. 100%, p<0.001). Importantly, a significantly higher number of water buffaloes as determined by nPCR were infected when reared jointly with bovines not subjected to tick control than when reared jointly with bovines subjected to tick control (B. bovis 31.6% vs. 9.5%, p<0.01; B. bigemina 42.1% vs. 9.5%, p<0.01, for water buffaloes reared with untreated vs. treated bovines) and/or when reared without bovines (B. bovis 31.6% vs. 11.6%, p<0.01; B. bigemina 42.1% vs. 20%, p<0.01). An accumulation of seropositivity and a decline of infection rates were observed in older animals, while differences observed with regard to gender may warrant further investigation. In summary, our findings suggest that water buffaloes are much more capable to limit or eliminate Babesia infection, possibly due to a more capable immune defense. Furthermore, an increased Babesia spp. parasite reservoir of bovines seems to increase the infection rate of water buffaloes when both are reared on the same pasture. PMID- 26827870 TI - Widespread presence of human-pathogenic Enterocytozoon bieneusi genotypes in chickens. AB - A total of 151 fecal specimens from chickens were randomly collected from local markets in Uberlandia and Belo Horizonte in the state of Minas Gerais, Brazil, to evaluate the presence of Enterocytozoon bieneusi by polymerase chain reaction (PCR). Enterocytozoon bieneusi was identified in 24 fecal samples (15.9%). This represents the first report of E. bieneusi in chickens in Brazil. All PCR positive specimens were sequenced and 4 genotypes were identified, Peru 6, Peru 11, Type IV, and D. All four genotypes have previously been reported as human pathogens and are potentially zoonotic. Our results demonstrate that human pathogenic E. bieneusi genotypes are present in chickens in Brazil, corroborating their potential role as a source of human infection and environmental contamination. PMID- 26827871 TI - Development of a quantitative PCR for the detection of Rangelia vitalii. AB - The aim of this study was to develop and validate a SYBR Green qPCR assay to detect and quantify a fragment of the 18S rRNA gene of Rangelia vitalii in canine blood. Repeatability of the qPCR was determined by the intra- and inter-assay variations. The qPCR showed efficiency of E=101.30 (r(2)=0.996), detecting as few as one copy of plasmid containing the target DNA. Specificity of the assay was performed using DNA samples of Babesia canis, B. gibsoni, Ehrlichia canis, E. ewingii and Leishmania sp. No cross-reactivity was observed. Field samples consisting of blood from 265 dogs from Porto Alegre, Brazil were also tested. A total of 24 (9.05%) samples were positive for R. vitalii. Amplicons of 50% of positive samples were confirmed to be R. vitalii by Sanger sequencing. The positive samples had an average of 3.5*10(5) organisms/mL of blood (range: 1.27*10(3)-1.88*10(6)) based on the plasmid-generated standard curve. In conclusion, the SYBR Green qPCR assay developed herein is sensitive and specific and can be used as a diagnostic tool for detection and quantification of R. vitalii in canine blood samples. PMID- 26827872 TI - IgG and IgM glycosylation patterns in patients undergoing image-guided tumor ablation. AB - BACKGROUND: Image-guided tumor ablation is a technique whereby needle-like applicators are placed directly into solid tumors under guidance typically with computed tomography or ultrasound. Changes in IgG and IgM antibody glycosylation were studied during ablation-induced immune response to cancer, and the use of glycosylation as a biomarker for diagnosis, prognosis and disease treatment was examined. METHODS: Plasma from 27 tumor patients was collected immediately before, after and for 6 months following ablation. IgG and IgM antibodies were isolated by use high-throughput chromatography, and analyzed by hydrophilic liquid chromatography. Thorough identification of glycan structures in each chromatography peak was performed by nano-liquid chromatography electrospray ionization mass spectrometry. RESULTS: Although antibody glycosylation was found to vary with cancer type, discernable patterns of change based on the successful treatment of tumors by ablation were not identified. One patient with renal clear cell carcinoma and poor disease outcome had unexpectedly high amount of oligomannose IgG glycans during the whole period of monitoring. In contrast, IgM antibodies did not follow the same pattern. CONCLUSIONS: These findings suggest that glycosylation patterns are indicative of an immune system that is unable to prevent different types of cancer, rather than products of the immunostimulatory response to the ablation of tumor itself. Analyses of the outcome effect suggested that IgG glycosylation and IgM glycosylation are not associated with tumor ablation. GENERAL SIGNIFICANCE: Present work opens a new way for parallel determination of glycosylation changes of both IgG and IgM antibodies by use of high-throughput methods, and their future use as biomarkers for disease diagnosis and prognosis. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc. PMID- 26827874 TI - Mobilization of hematopoietic stem cells with highest self-renewal by G-CSF precedes clonogenic cell mobilization peak. AB - Harvest of granulocyte colony-stimulating factor (G-CSF)-mobilized hematopoietic stem cells (HSCs) begins at day 5 of G-CSF administration, when most donors have achieved maximal mobilization. This is based on surrogate markers for HSC mobilization, such as CD34(+) cells and colony-forming activity in blood. However, CD34(+) cells or colony-forming units in culture (CFU-C) are heterogeneous cell populations with hugely divergent long-term repopulation potential on transplantation. HSC behavior is influenced by the vascular bed in the vicinity of which they reside. We hypothesized that G-CSF may mobilize sequentially cells proximal and more distal to bone marrow venous sinuses where HSCs enter the blood. We addressed this question with functional serial transplantation assays using blood and bone marrow after specific time points of G-CSF treatment in mice. We found that in mice, blood collected after only 48 hours of G-CSF administration was as enriched in serially reconstituting HSCs as blood collected at 5 days of G-CSF treatment. Similarly, mobilized Lin(-)CD34(+) cells were relatively enriched in more primitive Lin(-)CD34(+)CD38(-) cells at day 2 of G-CSF treatment compared with later points in half of human donors tested (n = 6). This suggests that in both humans and mice, hematopoietic progenitor and stem cells do not mobilize uniformly according to their maturation stage, with most potent HSCs mobilizing as early as day 2 of G-CSF. PMID- 26827873 TI - Fibrinogen Release and Deposition on Urinary Catheters Placed during Urological Procedures. AB - PURPOSE: Catheter associated urinary tract infections account for approximately 40% of all hospital acquired infections worldwide with more than 1 million cases diagnosed annually. Recent data from a catheter associated urinary tract infection animal model has shown that inflammation induced by catheterization releases host fibrinogen, which accumulates on the catheter. Further, Enterococcus faecalis catheter colonization was found to depend on EbpA (endocarditis and biofilm-associated pilus), a fibrinogen binding adhesin. We evaluated this mechanism in a human model. MATERIALS AND METHODS: Urinary catheters were collected from patients hospitalized for surgical or nonsurgical urological procedures. Catheters were subjected to immunofluorescence analyses by incubation with antifibrinogen antibody and then staining for fluorescence. Fluorescence intensity was compared to that of standard catheters. Catheters were incubated with strains of Enterococcus faecalis, Staphylococcus aureus or Candida to assess binding of those strains to fibrinogen laden catheters. RESULTS: After various surgical and urological procedures, 50 catheters were collected. In vivo dwell time ranged from 1 hour to 59 days. All catheters had fibrinogen deposition. Accumulation depended on dwell time but not on surgical procedure or catheter material. Catheters were probed ex vivo with E. faecalis, S. aureus and Candida albicans, which bound to catheters only in regions where fibrinogen was deposited. CONCLUSIONS: Taken together, these data show that urinary catheters act as a binding surface for the accumulation of fibrinogen. Fibrinogen is released due to inflammation resulting from a urological procedure or catheter placement, creating a niche that can be exploited by uropathogens to cause catheter associated urinary tract infections. PMID- 26827875 TI - Atypical twin-to-twin transfusion syndrome: prevalence in a population undergoing fetoscopic laser ablation of communicating placental vessels. AB - BACKGROUND: The diagnosis of twin-to-twin transfusion syndrome (TTTS) usually relies the presence of polyhydramnios in one sac with concomitant oligohydramnios in the other sac in a monochorionic diamniotic twin pregnancy. However, TTTS does not always show a linear progression and may present with cardiac compromise or critically abnormal Doppler velocimetry in either fetus before fluid measurements meet the typically used cutoff. OBJECTIVE: The aim of this study was to investigate the prevalence of atypical presentations of TTTS in a population undergoing laser fetoscopy. STUDY DESIGN: We performed a retrospective review of our database of TTTS laser fetoscopy from 2003 to the present. Our center is the regional referral center in the Pacific Northwest for minimally invasive treatment of complicated monochorionic twin pregnancies. Cases were labeled as "atypical" if fluid discordance did not meet formal TTTS criteria (oligohydramnios defined as maximum vertical pocket [MVP] <2 and polyhydramnios defined as MVP >8 before 20 weeks and >10 after 20 weeks). The rationale for consideration of laser fetoscopy was other evidence of severe TTTS such as significant cardiac compromise, evidence of twin anemia polycythemia sequence (TAPS), or persistent critically abnormal cord Dopplers. RESULTS: Three hundred seventy-nine cases of fetoscopic laser ablation for TTTS and its variants were available for review. Sixteen cases were excluded for a triplet pregnancy, 4 due to septostomy prior to referral to our center, 3 for monoamniotic pregnancy, and 11 for previous laser fetoscopy. Three hundred forty-five cases remained for evaluation. Among these, 25 cases were identified as "atypical," equaling 7.24% of our population. Eleven of these were for stage 3 recipient disease, 3 were for stage 4 recipient disease, 4 were for stage 3 both in recipient and donor, 4 were for stage 3 donor disease, and 3 were for spontaneous TAPS. CONCLUSION: In TTTS, severity of fetal compromise does not consistently correlate with fluid abnormalities meeting established criteria. This may be especially true in rapidly progressing cases. Attempts at rigid diagnostic amniotic fluid criteria may underestimate the severity and incidence of TTTS. This underscores the importance of careful surveillance, including arterial and venous Doppler velocimetry, of all monochorionic pregnancies. PMID- 26827876 TI - Preterm birth and its associations with residence and ambient vehicular traffic exposure. AB - BACKGROUND: Preterm birth (PTB) is a multifactorial disorder, and air pollution has been suggested to increase the risk of occurrence. However, large population studies controlling for multiple exposure measures in high-density settings with established commuter patterns are lacking. OBJECTIVE: We performed a geospatial analysis with the use of a publicly available database to identify whether residence during pregnancy, specifically with regard to exposure to traffic density and mobility in urban and suburban neighborhoods, may be a contributing risk factor for premature delivery. STUDY DESIGN: In our cohort study, we analyzed 9004 pregnancies with as many as 4900 distinct clinical and demographic variables from Harris County, Texas. On the basis of primary residency and occupational zip code information, geospatial analysis was conducted. Data on vehicle miles traveled (VMT) and percentages of inhabitants traveling to work were collected at the zip code level and additionally grouped by the three recognized regional commuter loop high-density thoroughfares resulting from two interstate/highway belts (inner, middle, and outer loops). PTB was categorized as late (34 1/7 to 36 6/7 weeks) and early PTB (22 1/7 to 33 6/7 weeks), and unadjusted odds ratios (OR) and adjusted ORs were ascribed. RESULTS: PTB prevalence in our study population was 10.1% (6.8% late and 3.3% early preterm), which is in accordance with our study and other previous studies. Prevalence of early PTB varied significantly between the regional commuter loop thoroughfares [OR for inner vs outer loop: 0.58 (95% confidence interval, 0.39-0.87), OR for middle vs outer loop, 0.74 (0.57-0.96)]. The ORs for PTB and early PTB were shown to be lower in gravidae from neighborhoods with the highest VMT/acre [OR for PTB, 0.82 (0.68-0.98), OR for early PTB, 0.78 (0.62-0.98)]. Conversely, risk of PTB and early PTB among subjects living in neighborhoods with a high percentage of inhabitants traveling to work over a greater distance demonstrated a contrary tendency [OR for PTB, 1.18 (1.03-1.35), OR for early PTB, 1.48 (1.17-1.86)]. In logistic regression models, the described association between PTB and residence withstood and could not be explained by differences in maternal age, gravidity or ethnicity, tobacco use, or history of PTB. CONCLUSION: While PTB is of multifactorial origin, the present study shows that community-based risk factors (namely urban/suburban location, differences in traffic density exposure, and need for traveling to work along high-vehicle density thoroughfares) may influence risk for PTB. Further research focusing on previously unrecognized community-based risk factors may lead to innovative future prevention measures. PMID- 26827877 TI - Relationship of trimester-specific smoking patterns and risk of preterm birth. AB - BACKGROUND: In 2011, the US national rate of smoking early in pregnancy was 11.5%. Unfortunately, our home state of Ohio had a rate twice as high at 23%. Smoking in pregnancy remains one of the most important modifiable risk factors for pregnancy complications, specifically preterm birth. OBJECTIVE: The objective of the study was to quantify the preterm birth risk to various trimester-specific smoking behaviors. STUDY DESIGN: The study was a population-based, retrospective cohort study of singleton non-anomalous live births, using Ohio birth records 2006 to 2012. Preterm birth rates were compared between non-smokers and women who smoked in the preconception period only, those who quit smoking after the 1st and 2nd trimesters, and those who smoked throughout pregnancy. Multivariate logistic regression quantified the risk of smoking with cessation at various times in pregnancy and preterm birth risk, adjusted for maternal race, education, age, Medicaid use, marital status, and parity. A stratified analysis was performed on the basis of preterm birth subtype: spontaneous preterm birth versus indicated preterm birth. We also performed an additional analysis stratifying for maternal race using the 2 largest categories of race (non-Hispanic white and non-Hispanic black). RESULTS: Of the 913,757 birth records analyzed, nearly 25% of the women reported some smoking behavior on the birth certificate data. Of smokers, less than half quit during pregnancy (38.8% vs 61.2% smoked throughout pregnancy). Early quitters had a similar preterm birth rate compared with non-smokers. Women who smoked through the 1st trimester only did not have a significant increase in their overall preterm birth odds ratio <37 weeks; however, it did increase the odds of extreme preterm birth <28 weeks by 20% (adjusted odds ratio, 1.20; 95% confidence interval [CI], 1.02, 1.40). Quitting late in pregnancy resulted in the highest odds ratio increase: 70% for preterm birth <37 weeks (adjusted odds ratio 1.70; CI, 1.60, 1.80), even after adjustment for the confounding influences. Quitting smoking early in pregnancy after the 1st trimester did not increase the overall risk of spontaneous or indicated preterm birth <37 weeks significantly. However, quitting after the 1st trimester was associated with a significant increase in risk of extreme spontaneous preterm birth <28 weeks, an effect not seen with indicated preterm birth <28 weeks. Delaying cessation until late in pregnancy-after the 2nd trimester-was associated with the highest risk increases, 65% increased odds of spontaneous and 78% increase in odds of indicated preterm births. The rate of preterm births to non-Hispanic black mothers was increased in all categories over those of non-Hispanic white mothers. The relative influence of smoking cessation in pregnancy was similar in black compared with white mothers. The effect modification in the regression model was analyzed and revealed no significant interaction between race and smoking patterns on preterm birth risk. CONCLUSION: Smoking throughout pregnancy is associated with an increased risk of preterm birth. However, quitting early in pregnancy negates this risk. Widespread programs aimed at smoking cessation early in pregnancy could have a significant impact on reducing the rate of preterm birth nationally. PMID- 26827878 TI - The effect of antidepressants on fertility. AB - BACKGROUND: Information on the effects of different pharmaceuticals on fertility is sparse. Human and animal models indicate that antidepressant use could have a negative effect on fertility through alteration of levels of the neurosteroid, allopregnanolone. OBJECTIVE: The objective of this study is to assess the effects of antidepressants on the natural fertility in women. STUDY DESIGN: A secondary analysis of data from Time to Conceive, a prospective cohort study, was conducted. Women ages 30 to 44 years without a history of infertility, early in their attempts to conceive, were followed with standardized pregnancy testing until pregnancy was detected. Medication use was assessed at enrollment, daily for up to 4 months, and then monthly. For this analysis, discrete time regression models were created to calculate the association between antidepressant use and fecundability. Potential confounders-age, body mass index, caffeine, alcohol use, and education-were included in all models. RESULTS: Ninety-two (9.6%) of 957 women reported antidepressant use while attempting to conceive. Women taking antidepressants were more likely to be non-Hispanic Caucasian (91% vs 75%, P < .01) and to consume alcoholic beverages (74% vs 61%, P < .01). Antidepressant use at enrollment had an adjusted fecundability ratio (FR) of 0.86 (95% confidence interval [CI], 0.63-1.20). However, time-varying analyses suggested that antidepressant use in a given cycle is associated with a reduced probability of conceiving in that cycle (adjusted FR, 0.75; 95% CI, 0.53-1.06). After adjusting for history of depression or restricting the analysis to women who reported a history of depression, the association between antidepressant use and decreased fecundability remained [adjusted FR, 0.66 (95% CI, 0.45-0.97) and (adjusted FR, 0.64; 95% CI, 0.43-0.94), respectively]. CONCLUSION: Our data suggest that antidepressants may reduce the probability of a woman with a history of depression to conceive naturally. Future studies are needed to differentiate the extent to which this association is due to the antidepressant itself versus the underlying depression. PMID- 26827879 TI - Association of the quality of interpersonal care during family planning counseling with contraceptive use. AB - BACKGROUND: Health communication and interpersonal skills are increasingly emphasized in the measurement of health care quality, yet there is limited research on the association of interpersonal care with health outcomes. As approximately 50% of pregnancies in the United States are unintended, whether interpersonal communication influences contraceptive use is of public health importance. OBJECTIVE: The aim of this study was to determine whether the quality of interpersonal care during contraceptive counseling is associated with contraceptive use over time. STUDY DESIGN: The Patient-Provider Communication about Contraception study is a prospective cohort study of 348 English-speaking women seen for contraceptive care, conducted between 2009 and 2012 in the San Francisco Bay Area. Quality of communication was assessed using a patient reported interpersonal quality in family planning care measure based on the dimensions of patient-centered care. In addition, the clinical visit was audio recorded and its content coded according to the validated Four Habits Coding Scheme to assess interpersonal communication behaviors of clinicians. The outcome measures were 6-month continuation of the selected contraceptive method and use of a highly or moderately effective method at 6 months. Results were analyzed using mixed effect logistic regression models controlling for patient demographics, the clinic and the provider at which the visit occurred, and the method selected. RESULTS: Patient participants had a mean age of 26.8 years (SD 6.9 years); 46% were white, 26% Latina, and 28% black. Almost two-thirds of participants had an income of <200% of the Federal Poverty Level. Most of the women (73%) were making visits to a provider whom they had not seen before. Of the patient participants, 41% were still using their chosen contraceptive method at 6-month follow-up. Patients who reported high interpersonal quality of family planning care were more likely to maintain use of their chosen contraceptive method (adjusted odds ratio [aOR], 1.8; 95% CI, 1.1-3.0) and to be using a highly or moderately effective method at 6 months (aOR, 2.0; 95% CI, 1.2-3.5). In addition, 2 of the Four Habits were associated with contraceptive continuation; "invests in the beginning" (aOR, 2.3; 95% CI, 1.2-4.3) and "elicits the patient's perspective" (aOR, 1.8; 95% CI, 1.0-3.2). CONCLUSION: Our study provides evidence that the quality of interpersonal care, measured using both patient report and observation of provider behaviors, influences contraceptive use. These results provide support for ongoing attention to interpersonal communication as an important aspect of health care quality. The associations of establishing rapport and eliciting the patient perspective with contraceptive continuation are suggestive of areas of focus for provider communication skills training for contraceptive care. PMID- 26827880 TI - Sequential plasma angiogenic factors levels in women with suspected preeclampsia. AB - BACKGROUND: Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester. OBJECTIVE: Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia. STUDY DESIGN: We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical Center, Boston, Massachusetts, for evaluation of preeclampsia at less than 37 weeks of gestation. Plasma samples were collected on admission and daily for the first 3 days and then weekly until delivery. Doppler ultrasound was performed on admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms-like tyrosine kinase and placental growth factor were measured on automated platform in a single batch after delivery and in a blinded fashion. Data are presented as median (25th to 75th centile), mean, or proportions as appropriate. RESULTS: During the study period, data from 100 women were analyzed for the study, and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, and lower birthweight and placental weight (all P < .01). These patients had higher soluble fms-like tyrosine kinase and soluble fms-like tyrosine kinase/placental growth factor ratio on admission and continued to have an increase in levels throughout hospital course. The median (25th to 75th) soluble fms-like tyrosine kinase/placental growth factor ratio among patients with adverse outcomes was 205.9 (72.5, 453.1) versus 47.5 (9.7, 87.0) among women without adverse outcomes (P < .001). The median (25th to 75th) absolute change per day in soluble fms-like tyrosine kinase levels (pg/mL) was 491.0 pg/mL (120.3, 1587.2) among women with adverse outcomes versus 81.3 pg/mL (-177.9, 449.0) among women without adverse outcomes (P = .01). Similarly the absolute change per day for soluble fms-like tyrosine kinase/placental growth factor ratio was 15.1 (1.8, 58.1) versus 2.7 (-0.6, 8.3) between the two groups (P = .004). The mean (range) days from admission to delivery was 6 (0-35) among subjects with soluble fms-like tyrosine kinase/placental growth factor ratio >=85 and 14 (0-39) below a ratio of 85 (P < .001). The positive predictive value for plasma soluble fms-like tyrosine kinase/placental growth factor ratio >=85 at admission for indicated delivery within 2 weeks was 91% (83-99%). Admission plasma soluble fms-like tyrosine kinase/placental growth factor ratio positively correlated with pre-delivery uterine artery resistive index (r = 0.35; P = .004). CONCLUSION: Among women admitted for evaluation of preeclampsia, women at risk for adverse pregnancy outcomes have higher soluble fms-like tyrosine kinase/placental growth factor ratio on admission, which continued to rise until delivery. Women with high soluble fms-like tyrosine kinase/placental growth factor ratios delivered sooner than women with low soluble fms-like tyrosine kinase/placental growth factor levels. These data support the hypothesis that targeting angiogenic imbalance in preeclampsia may lead to prolongation of pregnancy. PMID- 26827881 TI - Cerclage in twin pregnancy with dilated cervix between 16 to 24 weeks of gestation: retrospective cohort study. AB - BACKGROUND: Cervical dilation in the second trimester is associated with a greater than 90% rate of spontaneous preterm birth and a poor perinatal prognosis. OBJECTIVE: To compare the perinatal outcomes of twin pregnancies with dilated cervix in women who underwent either cerclage or expectant management. STUDY DESIGN: Retrospective cohort study of asymptomatic twin pregnancies identified with cervical dilation of >=1 cm at 16-24 weeks (1997-2014) at 7 institutions. Exclusion criteria were genetic or major fetal anomaly, multifetal reduction at >14 weeks, prior cerclage placement, monochorionic-monoamniotic placentation, active vaginal bleeding, labor, chorioamnionitis, elective termination of pregnancy, or medically indicated preterm birth. The primary outcome was incidence of spontaneous preterm birth at <34 weeks. Secondary outcomes were incidence of spontaneous preterm birth at <32 weeks, <28 weeks, and <24 weeks; perinatal mortality; and composite adverse neonatal outcome (respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and sepsis). RESULTS: A total of 76 women with twin pregnancy with dilated cervix of 1.0-4.5 cm were managed with either cerclage (n = 38) or expectant management (n = 38). Demographic characteristics were not significantly different. Analysis was adjusted for amniocentesis and vaginal progesterone use. In the cerclage group, 29 women (76%) received prophylactic indomethacin and 36 (94%) received prophylactic antibiotics, whereas the expectant management group did not. Interval from time at diagnosis of open cervix to delivery in the cerclage group was 10.46 +/- 5.6 weeks vs 3.7 +/- 3.2 weeks in the expectant management group, with a mean difference of 6.76 weeks (95% confidence interval [CI], 4.71-8.81). There were significant decreases in spontaneous preterm birth at <34 weeks (52.6% vs 94.7%; adjusted odds ratio [aOR], 0.06; 95% CI, 0.03 0.34), at <32 weeks (44.7% vs 89.4%; aOR, 0.08; 95% CI, 0.03-0.34); at <28 weeks (31.6% vs 89.4%; aOR, 0.05; 95% CI, 0.01-0.2); and at <24 weeks (13.1% vs 47.3%; aOR, 0.17; 95% CI, 0.05-0.54). There were also significant reductions in perinatal mortality (27.6% vs 59.2%; aOR, 0.24; 95% CI, 0.11-0.5), neonatal intensive care unit admission (75.9% vs 97.6%; aOR, 0.07; 95% CI, 0.01-0.66), and composite adverse neonatal outcome (33.9% vs 90.5%; aOR, 0.05; 95% CI, 0.01 0.21). CONCLUSION: Cerclage, indomethacin, and antibiotics in twin pregnancies with dilated cervix >=1 cm before 24 weeks were associated with significant longer latency period from diagnosis to delivery (6.7 weeks), decreased incidence of spontaneous preterm birth at any given gestational age, and improved perinatal outcome when compared with expectant management. PMID- 26827882 TI - Sarpagan-Ajmalan-Type Indoles: Biosynthesis, Structural Biology, and Chemo Enzymatic Significance. AB - The biosynthetic pathway of the monoterpenoid indole alkaloid ajmaline in the genus Rauvolfia, in particular Rauvolfia serpentina Benth. ex Kurz, is one of the few pathways that have been comprehensively uncovered. Every step in the progress of plant alkaloid biosynthesis research is due to the endeavors of several generations of scientists and the advancement of technologies. The tissue and cell suspension cultures developed in the 1970s by M.H. Zenk enabled the extraction of alkaloids and crude enzymes for use as experimental materials, thus establishing the foundation for further research on enzymatic reaction networks. In vivo NMR technology was first used in biosynthetic investigations in the 1990s following the invention of high-field cryo-NMR, which allowed the rapid and reliable detection of bioconversion processes within living plant cells. Shortly before, in 1988, a milestone was reached with the heterologous expression of the strictosidine synthase cDNA, which paved the way for the application of "reverse genetics" and "macromolecular crystallography." Both methods allowed the structural analysis of several Rauvolfia enzymes involved in ajmaline biosynthesis and expanded our knowledge of the enzyme mechanisms, substrate specificities, and structure-activity relationships. It also opened the door for rational enzyme engineering and metabolic steering. Today, the research focus of ajmaline biosynthesis is shifting from "delineation" to "utilization." The Pictet Spenglerase strictosidine synthase, strictosidine glucosidase, together with raucaffricine glucosidase, as pioneers in this area, have become useful tools to generate "privileged structures" and "diversity oriented" syntheses, which may help to construct novel scaffolds and to set up libraries of sarpagan-ajmalan type alkaloids in chemo-enzymatic approaches. PMID- 26827884 TI - The Chemistry of the Akuammiline Alkaloids. AB - An update on the literature covering the akuammiline family of alkaloids is presented. This chapter begins with a summary of new akuammiline alkaloids reported since 2000 and is followed by an overview of new reported bioactivities of akuammiline alkaloids since 2000. The remainder of the chapter comprises a comprehensive review of the synthetic chemistry that has been reported in the last 50 years concerning akuammiline alkaloids and their structural motifs. PMID- 26827883 TI - Sarpagine and Related Alkaloids. AB - The sarpagine-related macroline and ajmaline alkaloids share a common biosynthetic origin, and bear important structural similarities, as expected. These indole alkaloids are widely dispersed in 25 plant genera, principally in the family Apocynaceae. Very diverse and interesting biological properties have been reported for this group of natural products. Isolation of new sarpagine related alkaloids and the asymmetric synthesis of these structurally complex molecules are of paramount importance to the synthetic and medicinal chemists. A total of 115 newly isolated sarpagine-related macroline and ajmaline alkaloids, along with their physicochemical properties have been included in this chapter. A general and efficient strategy for the synthesis of these monomeric alkaloids, as well as bisindoles, has been presented, which involves application of the asymmetric Pictet-Spengler reaction (>98% ee) as a key step because of the ease of scale up of the tetracyclic template. Also included in this chapter are the syntheses of the sarpagine-related alkaloids, published since 2000. PMID- 26827885 TI - Monoterpenoid Bisindole Alkaloids. AB - This chapter covers the literature on bisindole alkaloids consisting of monoterpenoid indoles, published up to June 2015. Bisindole alkaloids isolated from plants belonging to the families Apocynaceae and Loganiaceae, including Iboga-vobasine type, Aspidosperma-Aspidosperma type, eburnan-Aspidosperma type, Strychnos-Strychnos type, macroline-macroline type, and so on, are described. Some recent syntheses of monoterpenoid bisindole alkaloids are outlined as well. PMID- 26827886 TI - Reduced germinal center follicular helper T cells but normal follicular regulatory T cells in the tonsils of a patient with a mutation in the PI3KR1 gene. PMID- 26827887 TI - Roles of inositol 1,4,5-trisphosphate receptors in spinocerebellar ataxias. AB - Modulation of the intracellular calcium concentration is a ubiquitous signaling system involved in the control of numerous biological processes in a wide variety of cells. Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), which act as calcium release channels in the ER membrane, play a key role in the regulation of intracellular calcium concentration. IP3R type 1 (IP3R1) is the major neuronal IP3R isoform in the central nervous system and particularly abundant in cerebellar Purkinje cells. Heterozygous deletions or missense mutations in ITPR1, which encodes IP3R1, result in autosomal dominantly inherited spinocerebellar ataxias (SCAs), including SCA types 15 (SCA15) and 29 (SCA29). In addition, homozygous missense mutations in carbonic anhydrase-related protein VIII (CARP), which suppresses the ability of IP3 to bind to IP3R1, cause a recessively inherited ataxia with mild cognitive impairment with/without quadrupedal gait. Moreover, cytosolic calcium overload with excessive IP3R1 activity has been implicated in the pathogenesis of other SCAs, including SCA types 2 (SCA2) and 3 (SCA3). These facts indicate that dysregulation of IP3R-mediated calcium signaling is linked to the pathogenesis of SCAs. Here, we focus on the molecular basis of SCA15 and SCA29, which are caused by mutations in ITPR1. In addition, we discuss other SCAs whose pathogenesis may be linked to aberrant activation of IP3R-mediated Ca(2+) signaling. PMID- 26827889 TI - The role of the microbial environment in Drosophila post-embryonic development. AB - Development, growth and maturation of animals are under genetic and environmental control. Multicellular organisms interact throughout their lives with a variety of environment- and body-associated microorganisms. It has now been appreciated that the very conspicuous and varied microbial population associated with the food and the gastro-intestinal tract is a critical factor that can influence growth. Beyond the phenomenology, the mechanisms underlying the beneficial effects of microbes on development are being revealed from studies in Drosophila melanogaster, a particularly well suited system for a mechanistic understanding of host/microbiota interactions. Association of otherwise germ-free eggs with specific bacterial strains isolated from Drosophila gut samples can accelerate growth in larvae raised on restrictive diets. We review advances made possible by the exploitation of such simplified gnotobiotic systems in the search for the genes, molecules and physiological adaptations responsible for this effect in both host and microbes. Transposon mutagenesis and gene-trait match studies in bacteria can identify the key microbial genes and metabolites required for the beneficial effect, acetic acid being one of them. In the fly, functional genomic analysis, transcriptomics and metabolomics point to the modulation of systemic insulin and steroid hormone signalling as well as the regulation of intestinal physiology, including the enhancement of intestinal protease activity, as crucial mediators of the host's response. PMID- 26827888 TI - Mosquito gut antiparasitic and antiviral immunity. AB - Mosquitoes are responsible for the transmission of diseases with a serious impact on global human health, such as malaria and dengue. All mosquito-transmitted pathogens complete part of their life cycle in the insect gut, where they are exposed to mosquito-encoded barriers and active factors that can limit their development. Here we present the current understanding of mosquito gut immunity against malaria parasites, filarial worms, and viruses such as dengue, Chikungunya, and West Nile. The most recently proposed immune mediators involved in intestinal defenses are discussed, as well as the synergies identified between the recognition of gut microbiota and the mounting of the immune response. PMID- 26827890 TI - Cervical spine evaluation in the bluntly injured patient. AB - BACKGROUND: Cervical spine injuries causing spinal cord trauma are rare in blunt trauma yet lead to devastating morbidity and mortality when they occur. There exists considerable debate in the literature about the best way for clinicians to proceed in ruling out cervical spine injuries in alert or obtunded blunt trauma patients. METHODS: We reviewed the current literature and practice management guidelines to generate clinical recommendations for the detection and clearance of cervical spine injuries in the blunt trauma patient. RESULTS: The NEXUS and Canadian C-Spine Rules are clinical tools to guide in the clearance of the cervical spine of patients who have sustained low risk trauma and who are pain free, with the Canadian C-Spine Rules having superior sensitivity and specificity. In the alert, high risk patient with pain (or without, if over the age of 65 years), follow up imaging is required. The best imaging modality to use is Computerized Tomography (CT) of the cervical spine. In the obtunded trauma patient, CT clearance of c-spine injury is adequate, unless there is soft tissue injury or any non-bony abnormalities detected. At such point, definitive clearance may be obtained with Magnetic Resonance Imaging (MRI). CONCLUSIONS: It is imperative to assume cervical spine injury in the blunt trauma patient. Clinical decision rules for cervical clearance may be used in low risk patients, avoiding imaging. High risk patients require imaging in the form of CT scan of the cervical spine. PMID- 26827891 TI - Anastomic leak in colorectal cancer surgery. Development of a diagnostic index (DIACOLE). AB - BACKGROUND: We have obtained a diagnostic score (DIACOLE) in order to detect anastomotic leakage in the postoperative period of colorectal cancer surgery. METHODS: Systematic review to identify any symptoms and clinical or analytical signs associated with anastomotic leakage after colorectal cancer surgery and a meta-analysis of each of these factors. The DIACOLE score encompasses all factors that reached statistical significance in their respective meta-analyses. The value of each factor in the score was determined depending the Napierian logarithm of the odds ratios. The index was validated using collected data at our institution. RESULTS: We identified 13 potential signs and symptoms of anastomotic leakage to elaborate the DIACOLE score. The predictive power of the DIACOLE was validated in a case-control study, resulting in an Area Under Curve (AUC) of 0.911 and a 95% confidence interval. These values were considered indicative of a very good diagnostic score. CONCLUSIONS: If DIACOLE score is > 3.065, a blood count and re-evaluating the score daily are recommended. If the DIACOLE>5.436, a radiological test is advised. We have developed free software to obtain DIACOLE value. PMID- 26827892 TI - Long-term results of robotic sacral hysteropexy for pelvic organ prolapse in China Single medical center. AB - OBJECTIVE: To evaluate the long-time clinical outcomes of robotic sacral hysteropexy for pelvic organ prolapse (POP). METHODS: Five women who underwent robotic sacral hysteropexy for the treatment for POP. Blood loss, operative time, length of stay, blood transfusion, pulmonary embolus, gastrointestinal or genitourinary tract injury, ileus, bowel obstruction, post-operative fever, and urinary retention were recorded for all patients. RESULTS: All the operative procedures were successfully performed using the robotic approach. In one case with perineal laceration, perineal repair was simultaneously performed, and in one patient with combined leiomyoma, myomectomy was performed first. The other three cases underwent no additional procedures during the surgery. Neither intra nor post-operative complications occurred in all 5 cases. After follow-up one year, all patients declared their satisfaction with the achieved anatomical and functional results. CONCLUSIONS: The robotic sacral hysteropexy is a minimally invasive technique for POP repair. We found low complication rates and high patient satisfaction with a minimum of 1 year followup. Larger series with longer follow-up data are needed to justify its widespread use. PMID- 26827893 TI - The impact of intraoperative vascular occlusion during liver surgery on postoperative peak ALT levels: A systematic review and meta-analysis. AB - BACKGROUND AND AIMS: Intraoperative vascular occlusion techniques during liver surgeries have been performed and refined for decades. However, the impact of these techniques on postoperative peak ALT levels remains uncertain. Thus, we performed a literature review and meta-analysis to determine the impact of intraoperative vascular occlusion during liver surgery on postoperative peak ALT levels. METHODS: A systematic literature search of the PubMed database was conducted to discover relevant controlled clinical trials. Studies that reported postoperative peak ALT values for both an observation group and a control group were included. The Q statistic and the I(2) index statistic were used to assess heterogeneity. Publication bias was evaluated using Egger's test and Orwin's fail safe N test. RESULTS: Of the 281 retrieved articles, 10 articles fulfilled the inclusion criteria. These 10 articles involved 12 randomized controlled trials with a total of 1443 records. The pooled estimation results indicated that intraoperative vascular occlusion significantly elevated postoperative peak ALT levels (test for SMD: Z = 4.09, P < 0.001; 95% CI: 0.59-1.68), with high heterogeneity (I(2) = 93.8%). Subgroup analysis revealed that intermittent inflow occlusion and Pringle's maneuver vascular occlusions may be the potential crucial factors. No obvious publication bias was detected by Egger's test (P = 0.541) or Orwin's fail-safe N test (Nfs0.05 = 2059.19). CONCLUSIONS: Intraoperative vascular occlusion, especially intermittent inflow occlusion and Pringle's maneuver vascular occlusions, may be a potential risk factor that could lead higher postoperative peak ALT values than non-occlusion procedures for liver surgeries. PMID- 26827894 TI - "See one, do one, teach one": Education and training in surgery and the correlation between surgical exposure with patients outcomes. PMID- 26827895 TI - Alcohol Drinking Mediates the Association between Polymorphisms of ADH1B and ALDH2 and Hepatitis B-Related Hepatocellular Carcinoma. AB - BACKGROUND: The role of polymorphisms on ADH1B and ALDH2 in patients with chronic hepatitis B is unclear. This study aims to examine whether alcohol drinking mediates the association between two ADH1B and ALDH2 polymorphisms and the risk of hepatocellular carcinoma among chronic hepatitis B patients. METHODS: A total of 3,824 individuals were enrolled in this study. Two SNPs, rs1229984 (ADH1B) and rs671 (ALDH2), were genotyped using the Affymetrix Axiom Genome-Wide CHB1 Array (Affymetrix, Inc). Multivariate unconditional logistic regression and mediation analyses were used, comparing CT or TT with CC for rs1229984 and GA and AA with GG for rs671. RESULTS: There were 602 cases of hepatocellular carcinoma and 3,222 controls. Frequencies of the rs1229984 (ADH1B) T allele and rs671 (ALDH2) A allele were 72.9% and 28.8%, respectively. Individuals who carried at least one deficient allele for both SNPs were significantly less likely to become habitual alcohol drinkers, with an OR and 95% confidence interval (CI) of 0.24 (0.15 0.40). Alleles for rs1229984 (ADH1B) and rs671 (ALDH2) were not associated with hepatocellular carcinoma in multivariate analyses. However, mediation analyses showed that the rs1229984 T allele, rs671 A allele, and two SNPs combined were significantly associated with decreased hepatocellular carcinoma risk, mediated through alcohol drinking, with an OR (95% CI) of 0.87 (0.79-0.96), 0.70 (0.61 0.82), and 0.73 (0.58-0.88), respectively. CONCLUSIONS: Polymorphisms on ADH1B and ALDH2 had significant indirect effects on hepatocellular carcinoma risk, mediated through alcohol drinking. IMPACT: Future genetic studies of chronic hepatitis B and hepatocellular carcinoma must take mediation effects into consideration. Cancer Epidemiol Biomarkers Prev; 25(4); 693-9. (c)2016 AACR. PMID- 26827897 TI - New insights on pyrimidine signalling within the arterial vasculature - Different roles for P2Y2 and P2Y6 receptors in large and small coronary arteries of the mouse. AB - Extracellular pyrimidines activate P2Y receptors on both smooth muscle cells and endothelial cells, leading to vasoconstriction and relaxation respectively. The aim of this study was to utilize P2Y knock-out (KO) mice to determine which P2Y receptor subtype are responsible for the contraction and relaxation in the coronary circulation and to establish whether P2Y receptors have different functions along the mouse coronary vascular tree. We tested stable pyrimidine analogues on isolated coronary arteries from P2Y2 and P2Y6 receptor KO mice in a myograph setup. In larger diameter segments of the left descending coronary artery (LAD) (lumen diameter~150MUm) P2Y6 is the predominant contractile receptor for both UTP (uridine triphosphate) and UDP (uridine diphosphate) induced contraction. In contrast, P2Y2 receptors mediate endothelial-dependent relaxation. However, in smaller diameter LAD segments (lumen diameter~50MUm), the situation is opposite, with P2Y2 being the contractile receptor and P2Y6 functioning as a relaxant receptor along with P2Y2. Immunohistochemistry was used to confirm smooth muscle and endothelial localization of the receptors. In vivo measurements of blood pressure in WT mice revealed a biphasic response to the stable analogue UDPbetaS. Based on the changes in P2Y receptor functionality along the mouse coronary arterial vasculature, we propose that UTP can act as a vasodilator downstream of its release, after being degraded to UDP, without affecting the contractile pyrimidine receptors. We also propose a model, showing physiological relevance for the changes in purinergic receptor functionality along the mouse coronary vascular tree. PMID- 26827896 TI - Ryanodine receptor sensitivity governs the stability and synchrony of local calcium release during cardiac excitation-contraction coupling. AB - Calcium-induced calcium release is the principal mechanism that triggers the cell wide [Ca(2+)]i transient that activates muscle contraction during cardiac excitation-contraction coupling (ECC). Here, we characterize this process in mouse cardiac myocytes with a novel mathematical action potential (AP) model that incorporates realistic stochastic gating of voltage-dependent L-type calcium (Ca(2+)) channels (LCCs) and sarcoplasmic reticulum (SR) Ca(2+) release channels (the ryanodine receptors, RyR2s). Depolarization of the sarcolemma during an AP stochastically activates the LCCs elevating subspace [Ca(2+)] within each of the cell's 20,000 independent calcium release units (CRUs) to trigger local RyR2 opening and initiate Ca(2+) sparks, the fundamental unit of triggered Ca(2+) release. Synchronization of Ca(2+) sparks during systole depends on the nearly uniform cellular activation of LCCs and the likelihood of local LCC openings triggering local Ca(2+) sparks (ECC fidelity). The detailed design and true SR Ca(2+) pump/leak balance displayed by our model permits investigation of ECC fidelity and Ca(2+) spark fidelity, the balance between visible (Ca(2+) spark) and invisible (Ca(2+) quark/sub-spark) SR Ca(2+) release events. Excess SR Ca(2+) leak is examined as a disease mechanism in the context of "catecholaminergic polymorphic ventricular tachycardia (CPVT)", a Ca(2+)-dependent arrhythmia. We find that that RyR2s (and therefore Ca(2+) sparks) are relatively insensitive to LCC openings across a wide range of membrane potentials; and that key differences exist between Ca(2+) sparks evoked during quiescence, diastole, and systole. The enhanced RyR2 [Ca(2+)]i sensitivity during CPVT leads to increased Ca(2+) spark fidelity resulting in asynchronous systolic Ca(2+) spark activity. It also produces increased diastolic SR Ca(2+) leak with some prolonged Ca(2+) sparks that at times become "metastable" and fail to efficiently terminate. There is a huge margin of safety for stable Ca(2+) handling within the cell and this novel mechanistic model provides insight into the molecular signaling characteristics that help maintain overall Ca(2+) stability even under the conditions of high SR Ca(2+) leak during CPVT. Finally, this model should provide tools for investigators to examine normal and pathological Ca(2+) signaling characteristics in the heart. PMID- 26827899 TI - "Young at heart": Regenerative potential linked to immature cardiac phenotypes. AB - The adult human myocardium is incapable of regeneration; yet, the zebrafish (Danio rerio) can regenerate damaged myocardium. Similar to the zebrafish heart, hearts of neonatal, but not adult mice are capable of myocardial regeneration. We performed a proteomics analysis of adult zebrafish hearts and compared their protein expression profile to hearts from neonatal and adult mice. Using difference in-gel electrophoresis (DIGE), there was little overlap between the proteome from adult mouse (>8weeks old) and adult zebrafish (18months old) hearts. Similarly, there was a significant degree of mismatch between the protein expression in neonatal and adult mouse hearts. Enrichment analysis of the selected proteins revealed over-expression of DNA synthesis-related proteins in the cardiac proteome of the adult zebrafish heart similar to neonatal and 4days old mice, whereas in hearts of adult mice there was a mitochondria-related predominance in protein expression. Importantly, we noted pronounced differences in the myofilament composition: the adult zebrafish heart lacks many of the myofilament proteins of differentiated adult cardiomyocytes such as the ventricular isoforms of myosin light chains and nebulette. Instead, troponin I and myozenin 1 were expressed as skeletal isoforms rather than cardiac isoforms. The relative immaturity of the adult zebrafish heart was further supported by cardiac microRNA data. Our assessment of zebrafish and mammalian hearts challenges the assertions on the translational potential of cardiac regeneration in the zebrafish model. The immature myofilament composition of the fish heart may explain why adult mouse and human cardiomyocytes lack this endogenous repair mechanism. PMID- 26827898 TI - Moderate intensity exercise prevents diabetic cardiomyopathy associated contractile dysfunction through restoration of mitochondrial function and connexin 43 levels in db/db mice. AB - AIMS: Although the cardiovascular benefits of exercise are well known, exercise induced effects and mechanisms in prevention of cardiomyopathy are less clear during obesity associated type-2 diabetes. The current study assessed the impact of moderate intensity exercise on diabetic cardiomyopathy by examining cardiac function and structure and mitochondrial function. METHODS: Obese-diabetic (db/db), and lean control (db/+) mice, were subjected to a 5 week, 300 m run on a tread-mill for 5 days/week at the speeds of 10-11 m/min. Various physiological parameters were recorded and the heart function was evaluated with M-mode echocardiography. Contraction parameters and calcium transits were examined on isolated cardiomyocytes. At the molecular level: connexin 43 and 37 (Cx43 and 37) levels, mitochondrial biogenesis regulators: Mfn2 and Drp-1 levels, mitochondrial trans-membrane potential and cytochrome c leakage were assessed through western blotting immunohistochemistry and flow cytometry. Ability of exercise to reverse oxygen consumption rate (OCR), tissue ATP levels, and cardiac fibrosis were also determined. RESULTS: The exercise regimen was able to prevent diabetic cardiac functional deficiencies: ejection fraction (EF) and fractional shortening (FS). Improvements in contraction velocity and contraction maximum were noted with the isolated cardiomyocytes. Restoration of interstitial and micro-vessels associated Cx43 levels and improved gap junction intercellular communication (GJIC) were observed. The decline in the Mfn2/Drp-1 ratio in the db/db mice hearts was prevented after exercise. The exercise regimen further attenuated transmembrane potential decline and cytochrome c leakage. These corrections further led to improvements in OCR and tissue ATP levels and reduction in cardiac fibrosis. CONCLUSIONS: Moderate intensity exercise produced significant cardiovascular benefits by improving mitochondrial function through restoration of Cx43 networks and mitochondrial trans-membrane potential and prevention of excessive mitochondrial fission. PMID- 26827900 TI - Effect of triclosan, triclocarban, 2,2',4,4'-tetrabromodiphenyl ether, and bisphenol A on the iodide uptake, thyroid peroxidase activity, and expression of genes involved in thyroid hormone synthesis. AB - Triclosan, triclocarban, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), and bisphenol A (BPA) have been reported to disturb thyroid hormone (TH) homeostasis. We have examined the effects of these chemicals on sodium/iodide symporter (NIS) mediated iodide uptake and the expression of genes involved in TH synthesis in rat thyroid follicular FRTL-5 cells, and on the activity of thyroid peroxidase (TPO) using rat thyroid microsomes. All four chemicals inhibited NIS-mediated iodide uptake in a concentration-dependent manner. A decrease in the iodide uptake was also observed in the absence of sodium iodide. Kinetic studies showed that all four chemicals were non-competitive inhibitors of NIS, with the order of Ki values being triclosan300 MUM, respectively. Neither BDE-47 nor BPA affected TPO activity. In conclusion, triclosan, triclocarban, BDE-47, and BPA inhibited iodide uptake, but had differential effects on the expression of TH synthesis-related genes and the activity of TPO. PMID- 26827901 TI - Vaccinia-related kinase 1 is required for early uterine development in Caenorhabditis elegans. AB - Protein kinases regulate a multitude of processes by reversible phosphorylation of target molecules. Induction of cell proliferation and differentiation are fundamental to development and rely on tightly controlled kinase activities. Vaccinia-Related Kinases (VRKs) have emerged as a multifunctional family of kinases with essential functions conserved, from nematodes and fruit flies, to humans. VRK substrates include chromatin and transcription factors, whereas deregulation of VRKs is implicated in sterility, cancer and neurological defects. In contrast to previous observations, we describe here that Caenorhabditis elegans VRK-1 is expressed in all cell types, including proliferating and post mitotic cells. Despite the ubiquitous expression pattern, we find that vrk-1 mutants are particularly impaired in uterine development. Our data show that VRK 1 is required for uterine cell proliferation and differentiation. Moreover, the anchor cell, a specialized uterine cell, fails to fuse with neighboring cells to form the utse syncytium in vrk-1 mutants, thus providing further insight on the role of VRKs in organogenesis. PMID- 26827903 TI - Synthesis, characterization and thermotropic phase behavior of a homologous series of N-acyl-L-alaninols and interaction of N-myristoyl L-alaninol with dimyristoylphosphatidylcholine. AB - N-acylethanolamines (NAEs) and their precursors, N-acylphosphatidylethanolamines are present in the cell membranes of a variety of species and exhibit interesting biological properties. N-acyl-L-alaninols (NAAOHs) are chiral homologues of NAEs and reduced forms of N-acyl-L-alanines (NAAs) and were reported to induce apoptosis in human lymphocytes. In the present study, we have synthesized and characterized a homologous series of N-acyl-L-alaninols (n=9-20). In DSC studies in the dry as well as hydrated states NAAOHs with different chain lengths showed single sharp transitions similar to N-acyl-L-alanines. Transition enthalpies (DeltaHt) and entropies (DeltaSt) of NAAOHs are linearly dependent on the acyl chain length in both dry and hydrated states. Powder X-ray diffraction studies showed that the d-spacings of NAAOHs exhibit linear dependence on the chain length and the incremental increase in the d values suggest that they may be packed in a tilted bilayer pattern. Studies on the interaction of N-myristoyl L alaninol (NMAOH) with DMPC revealed that the two amphiphiles mix well up to 45 mol% of NMAOH, whereas phase separation is observed at higher contents of the alaninol. Transmission electron microscopic studies show that the NMAOH:DMPC (45:55, mol/mol) mixture forms unilamellar vesicles of about 120-150 nm in diameter. PMID- 26827902 TI - Epithelial cell fate in the nephron tubule is mediated by the ETS transcription factors etv5a and etv4 during zebrafish kidney development. AB - Kidney development requires the differentiation and organization of discrete nephron epithelial lineages, yet the genetic and molecular pathways involved in these events remain poorly understood. The embryonic zebrafish kidney, or pronephros, provides a simple and useful model to study nephrogenesis. The pronephros is primarily comprised of two types of epithelial cells: transportive and multiciliated cells (MCCs). Transportive cells occupy distinct tubule segments and are characterized by the expression of various solute transporters, while MCCs function in fluid propulsion and are dispersed in a "salt-and-pepper" fashion within the tubule. Epithelial cell identity is reliant on interplay between the Notch signaling pathway and retinoic acid (RA) signaling, where RA promotes MCC fate by inhibiting Notch activity in renal progenitors, while Notch acts downstream to trigger transportive cell formation and block adoption of an MCC identity. Previous research has shown that the transcription factor ets variant 5a (etv5a), and its closely related ETS family members, are required for ciliogenesis in other zebrafish tissues. Here, we mapped etv5a expression to renal progenitors that occupy domains where MCCs later emerge. Thus, we hypothesized that etv5a is required for normal development of MCCs in the nephron. etv5a loss of function caused a decline of MCC number as indicated by the reduced frequency of cells that expressed the MCC-specific markers outer dense fiber of sperm tails 3b (odf3b) and centrin 4 (cetn4), where rescue experiments partially restored MCC incidence. Interestingly, deficiency of ets variant 4 (etv4), a related gene that is broadly expressed in the posterior mesoderm during somitogenesis stages, also led to reduced MCC numbers, which were further reduced by dual etv5a/4 deficiency, suggesting that both of these ETS factors are essential for MCC formation and that they also might have redundant activities. In epistatic studies, exogenous RA treatment expanded the etv5a domain within the renal progenitor field and RA inhibition blocked etv5a in this populace, indicating that etv5a acts downstream of RA. Additionally, treatment with exogenous RA partially rescued the reduced MCC phenotype after loss of etv5a. Further, abrogation of Notch with the small molecule inhibitor DAPT increased the renal progenitor etv5a expression domain as well as MCC density in etv5a deficient embryos, suggesting Notch acts upstream to inhibit etv5a. In contrast, etv4 levels in renal progenitors were unaffected by changes in RA or Notch signaling levels, suggesting a possible non-cell autonomous role during pronephros formation. Taken together, these findings have revealed new insights about the genetic mechanisms of epithelial cell development during nephrogenesis. PMID- 26827905 TI - Impact of the 2014 Food and Drug Administration Warnings Against Power Morcellation. AB - STUDY OBJECTIVE: To determine whether members of the AAGL Advancing Minimally Invasive Gynecologic Surgery Worldwide (AAGL) and members of the American College of Obstetricians and Gynecologists Collaborative Ambulatory Research Network (ACOG CARN) have changed their clinical practice based on the 2014 Food and Drug Administration (FDA) warnings against power morcellation. DESIGN: A survey study. SETTING: Participants were invited to complete this online survey (Canadian Task Force classification II-2). PATIENTS: AAGL and ACOG CARN members. INTERVENTIONS: An online anonymous survey with 24 questions regarding demographics and changes to clinical practice during minimally invasive myomectomies and hysterectomies based on the 2014 FDA warnings against power morcellation. MEASUREMENTS AND MAIN RESULTS: A total of 615 AAGL members and 54 ACOG CARN members responded (response rates of 8.2% and 60%, respectively). Before the FDA warnings, 85.8% and 86.9%, respectively, were using power morcellation during myomectomies and hysterectomies. After the FDA warnings, 71.1% and 75.8% of respondents reported stopping the use of power morcellation during myomectomies and hysterectomies. The most common reasons cited for discontinuing the use of power morcellation or using it less often were hospital mandate (45.6%), the concern for legal consequences (16.1%), and the April 2014 FDA warning (13.9%). Nearly half of the respondents (45.6%) reported an increase in their rate of laparotomy. Most (80.3%) believed that the 2014 FDA warnings have not led to an improvement in patient outcomes and have led to harming patients (55.1%). CONCLUSION: AAGL and ACOG CARN respondents reported decreased use of power morcellation during minimally invasive gynecologic surgery after the 2014 FDA warnings, the most common reason cited being hospital mandate. Rates of laparotomy have increased. Most members surveyed believe that the FDA warnings have not improved patient outcomes. PMID- 26827904 TI - Maximally asymmetric transbilayer distribution of anionic lipids alters the structure and interaction with lipids of an amyloidogenic protein dimer bound to the membrane surface. AB - We used molecular dynamics simulations to explore the effects of asymmetric transbilayer distribution of anionic phosphatidylserine (PS) lipids on the structure of a protein on the membrane surface and subsequent protein-lipid interactions. Our simulation systems consisted of an amyloidogenic, beta-sheet rich dimeric protein (D42) absorbed to the phosphatidylcholine (PC) leaflet, or protein-contact PC leaflet, of two membrane systems: a single-component PC bilayer and double PC/PS bilayers. The latter comprised of a stable but asymmetric transbilayer distribution of PS in the presence of counterions, with a 1-component PC leaflet coupled to a 1-component PS leaflet in each bilayer. The maximally asymmetric PC/PS bilayer had a non-zero transmembrane potential (TMP) difference and higher lipid order packing, whereas the symmetric PC bilayer had a zero TMP difference and lower lipid order packing under physiologically relevant conditions. Analysis of the adsorbed protein structures revealed weaker protein binding, more folding in the N-terminal domain, more aggregation of the N- and C terminal domains and larger tilt angle of D42 on the PC leaflet surface of the PC/PS bilayer versus the PC bilayer. Also, analysis of protein-induced membrane structural disruption revealed more localized bilayer thinning in the PC/PS versus PC bilayer. Although the electric field profile in the non-protein-contact PS leaflet of the PC/PS bilayer differed significantly from that in the non protein-contact PC leaflet of the PC bilayer, no significant difference in the electric field profile in the protein-contact PC leaflet of either bilayer was evident. We speculate that lipid packing has a larger effect on the surface adsorbed protein structure than the electric field for a maximally asymmetric PC/PS bilayer. Our results support the mechanism that the higher lipid packing in a lipid leaflet promotes stronger protein-protein but weaker protein-lipid interactions for a dimeric protein on membrane surfaces. PMID- 26827906 TI - Long term outcome of patients with low level of cryoglobulin (<0.05g/L). AB - OBJECTIVES: To date, no studies have yet assessed the characteristics of non-HCV patients with low level of cryoglobulin (<=0.05 g/L). The aims of the current study were thus to: 1) determine the prevalence of cryoglobulin <=0.05 g/L in patients with non-HCV cryoglobulin; and 2) compare clinical features and long term outcome, including organ complications and mortality rate, between non-HCV patients with cryoglobulin level <=0.05 g/L and those exhibiting cryoglobulin level >0.05 g/L. METHODS: Among 6379 cryoglobulin testing, cryoglobulin was detected in 618 patients (9.69% of cases); of these 618 patients, 453 non-HCV patients were included in the study. The medical records of these patients were reviewed. RESULTS: Of the 453 non-HCV cryoglobulin-positive patients, 265 (58.6%) exhibited cryoglobulin level <=0.05 g/L. We showed that patients with cryoglobulin level <=0.05 g/L had: 1) less commonly: palpable purpura (p<0.001), digital ulcers (p=0.006), peripheral neurologic involvement (p=0.03) and renal impairment (p=0.03); and 2) lower median values of ESR (p<0.001) and C-reactive protein (p=0.001). The patients with cryoglobulin level <=0.05 g/L less often experienced infections (p=0.04) and hematological malignancies (p=0.01); both groups did not differ regarding prevalence of connective tissue diseases and solid tumors. Mortality rate was as high as 13.6% in patients with cryoglobulin level <=0.05 g/L; death was mainly due to: solid tumors (16.6%), cardiovascular complications (13.8%), hematological malignancies (11.1%), infections (8.3%), pulmonary/renal complications of cryoglobulin (8.3%) and connective tissue diseases (8.3%). CONCLUSION: Our study shows a high prevalence of cryoglobulin level <=0.05 g/L in clinical practice. Our findings further underscore that non HCV cryoglobulin level <=0.05 g/L may be responsible for severe renal and neurological complications, leading to high morbidity and mortality in these patients. Thus, our data suggest that both appropriate therapy and close follow up may be required to improve such patients' outcome. PMID- 26827907 TI - The hidden world of anti-phospholipid antibodies and female infertility: A literature appraisal. AB - Even though the association of anti-phospholipid antibodies (aPL) with infertility is debated, infertile women are commonly screened for aPL. To review evidence, a systematic PubMed search was conducted to retrieve papers addressing (i) the association between aPL and infertility, (ii) the positivity rate of criteria and non-criteria aPL in women with infertility, (iii) the association between aPL and assisted reproduction technologies (ART) outcome, (iv) the efficacy of medical treatments on ART outcome, and (v) the effects of ART on thrombotic risk. A total of 46 papers were considered; several limitations emerged: (i) wide heterogeneity in study populations, (ii) non-prospective design in 90% of studies, and (iii) aPL cutoffs not conforming to international guidelines in more than 75% of studies; aPL positivity not confirmed in 89% of studies. Most studies evinced an association between infertility and anti beta2GPI antibodies and almost all non-criteria aPL. The association rate with infertility was below 50% for lupus anti-coagulant, anti-cardiolipin antibodies (aCL), and anti-phosphatidic acid antibodies. According to our estimates, overall positivity rates of criteria and non-criteria aPL tests are 6% and 3% among infertile women, 1% and 2% among controls, respectively. A significant difference in the positivity rate of patients versus controls emerged for aCL only. Five of 18 studies reported a detrimental effect of aPL on ART outcome. Only one of the six studies assessing the effects of treatment on ART outcome among aPL-positive infertile women reported a benefit. All relevant studies reported no increase in the rate of thrombosis among aPL-positive women undergoing ART. PMID- 26827908 TI - Sjogren's syndrome and multiple sclerosis: Two sides of the same coin? PMID- 26827909 TI - Autoantibody Production in Cancer--The Humoral Immune Response toward Autologous Antigens in Cancer Patients. AB - A link between autoimmune responses and cancer via autoantibodies was first described in the 1950s. Since, autoantibodies have been studied for their potential use as cancer biomarkers, however the exact causes of their production remain to be elucidated. This review summarizes current theories of the causes of autoantibody production in cancer, namely: 1) defects in tolerance and inflammation, 2) changes in protein expression levels, 3) altered protein structure, and 4) cellular death mechanisms. We also highlight the need for further research into this field to improve our understanding of autoantibodies as biomarkers for cancer development and progression. PMID- 26827910 TI - Impairment of object recognition memory by maternal bisphenol A exposure is associated with inhibition of Akt and ERK/CREB/BDNF pathway in the male offspring hippocampus. AB - Bisphenol A (BPA) is a commonly used endocrine-disrupting chemical used as a component of polycarbonates plastics that has potential adverse effects on human health. Exposure to BPA during development has been implicated in memory deficits, but the mechanism of action underlying the effect is not fully understood. In this study, we investigated the effect of maternal exposure to BPA on object recognition memory and the expressions of proteins important for memory, especially focusing on the ERK/CREB/BDNF pathway. Pregnant Sprague-Dawley female rats were orally treated with either vehicle or BPA (0.05, 0.5, 5 or 50 mg/kg BW/day) during days 9-20 of gestation. Male offspring were tested on postnatal day 21 with the object recognition task. Recognition memory was assessed using the object recognition index (index=the time spent exploring the novel object/(the time spent exploring the novel object+the time spent exploring the familiar object)). In the test session performed 90 min after the training session, BPA-exposed male offspring not only spent more time in exploring the familiar object at the highest dose than the control, but also displayed a significantly decreased the object recognition index at the doses of 0.5, 5 and 50 mg/kg BW/day. During the test session performed 24h after the training session, BPA-treated males did not change the time spent exploring the familiar object, but had a decreased object recognition index at 5 and 50 mg/kg BW/day, when compared to control group. These findings indicate that object recognition memory was susceptible to maternal BPA exposure. Western blot analysis of hippocampi from BPA-treated male offspring revealed a decrease in Akt, phospho Akt, p44/42 MAPK and phospho-p44/42 MAPK protein levels, compared to controls. In addition, BPA significantly inhibited the levels of phosphorylation of CREB and BDNF in the hippocampus. Our results show that maternal BPA exposure may full impair object recognition memory, and that impairment may be related to a decrease in Akt activation and an inhibition of the ERK/CREB/BDNF pathway in the hippocampus. This study also adds new evidence that suggests BPA has an antagonistic effect on the action of estrogen in the brain. PMID- 26827911 TI - Challenges in the clinical assessment of novel tuberculosis drugs. AB - To tackle the global TB epidemic effectively, novel treatment strategies are critically needed to shorten the duration of TB therapy and treat drug-resistant TB. Drug development for TB, stymied for decades, has enjoyed a renaissance over the past several years. However, the development of new TB regimens is hindered by the limitations in our understanding and use of preclinical models; the paucity of accurate, early surrogate markers of cure, and challenges in untangling the individual contributions of drugs to multidrug regimens in a complex, multi-compartment disease. Lack of profit motive, advocacy, and imagination has contributed mightily to the dearth of drugs we have on the shelf to treat this ancient disease. Areas that will speed the development of new regimens for TB include novel murine and in vitro pharmacodynamics models, clinical endpoints that are not culture-based, innovative clinical trial designs, and an infusion of much-needed funding. PMID- 26827913 TI - Bronchodilator effects, pharmacokinetics and safety of PSX1002-GB, a novel glycopyrronium bromide formulation, in COPD patients; a randomised crossover study. AB - AIMS: To establish the dose-response relationship for pharmacodynamics (bronchodilatation), safety and pharmacokinetics of a novel particle engineered formulation of Glycopyrronium bromide (PSX1002-GB) in patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients with moderate to severe COPD with bronchodilator reversible lung function were enrolled into this randomized, placebo-controlled, double-blind, dose-ranging, single dose, five way cross-over study (n = 37). Patients received single doses of PSX1002-GB (12.5-100 MUg) via pMDI with one-week washouts between treatments. RESULTS: PSX1002-GB caused a bronchodilator response observed at 5 min post-dose at all doses. Significant improvements in mean change from baseline FEV1 at 24 h were seen at all doses compared with placebo; Mean changes were 0.071L (95% CI 0.041-0.101), 0.087L (95% CI 0.056-0.118), 0.102L (95% CI 0.072-0.133) and 0.120L (95% CI 0.089 0.150) for 12.5, 25, 50 and 100 MUg respectively. PSX1002-GB 50 and 100 mcg caused rapid bronchodilation at 5 min after dosing. PSX1002-GB was well tolerated with similar adverse event rates reported compared to placebo. There were no clinically relevant changes in heart rate, blood pressure or ECG parameters (including QTc interval). CONCLUSION: Single doses of PSX1002-GB (12.5-100 MUg) were well tolerated. PSX1002-GB 50 and 100 mcg delivered by pMDI produced rapid onset bronchodilation that was sustained over a 24 h period. PMID- 26827914 TI - Quantitative and qualitative transcriptome analysis of four industrial strains of Claviceps purpurea with respect to ergot alkaloid production. AB - The fungus Claviceps purpurea is a biotrophic phytopathogen widely used in the pharmaceutical industry for its ability to produce ergot alkaloids (EAs). The fungus attacks unfertilized ovaries of grasses and forms sclerotia, which represent the only type of tissue where the synthesis of EAs occurs. The biosynthetic pathway of EAs has been extensively studied; however, little is known concerning its regulation. Here, we present the quantitative transcriptome analysis of the sclerotial and mycelial tissues providing a comprehensive view of transcriptional differences between the tissues that produce EAs and those that do not produce EAs and the pathogenic and non-pathogenic lifestyle. The results indicate metabolic changes coupled with sclerotial differentiation, which are likely needed as initiation factors for EA biosynthesis. One of the promising factors seems to be oxidative stress. Here, we focus on the identification of putative transcription factors and regulators involved in sclerotial differentiation, which might be involved in EA biosynthesis. To shed more light on the regulation of EA composition, whole transcriptome analysis of four industrial strains differing in their alkaloid spectra was performed. The results support the hypothesis proposing the composition of the amino acid pool in sclerotia to be an important factor regulating the final structure of the ergopeptines produced by Claviceps purpurea. PMID- 26827916 TI - Ventromedial prefrontal damage causes a pervasive impairment of episodic memory and future thinking. AB - The ability to project oneself into the past and future to relive or pre-live personal experiences, known as mental time travel (MTT), is associated with activity in a core network of brain regions involving the ventromedial prefrontal cortex (vmPFC). We investigated whether (1) vmPFC is crucial for MTT, and (2) whether vmPFC is selectively involved in the construction of self-relevant events or also mediates construction of events happening to others. Patients with lesions to vmPFC (vmPFC patients) and healthy controls remembered personal past events and imagined personal future events across different timeframes, and imagined events to happen to a close or a distant other. Compared to the controls, vmPFC patients were impaired at constructing both past and future events, indicating that vmPFC is critical for MTT. vmPFC patients' ability to imagine personal future events was related to patients' temporal discounting rates. Patients, however, were also impaired at imagining other-related events, suggesting that self-relevance may not be a critical factor in explaining vmPFC's involvement in MTT. We suggest that vmPFC is crucial for the imagination of complex experiences alternative to the current reality, which serves construction of both self-relevant and other-relevant events. PMID- 26827917 TI - The neural dynamics of stimulus and response conflict processing as a function of response complexity and task demands. AB - Both stimulus and response conflict can disrupt behavior by slowing response times and decreasing accuracy. Although several neural activations have been associated with conflict processing, it is unclear how specific any of these are to the type of stimulus conflict or the amount of response conflict. Here, we recorded electrical brain activity, while manipulating the type of stimulus conflict in the task (spatial [Flanker] versus semantic [Stroop]) and the amount of response conflict (two versus four response choices). Behaviorally, responses were slower to incongruent versus congruent stimuli across all task and response types, along with overall slowing for higher response-mapping complexity. The earliest incongruency-related neural effect was a short-duration frontally distributed negativity at ~200 ms that was only present in the Flanker spatial conflict task. At longer latencies, the classic fronto-central incongruency related negativity 'N(inc)' was observed for all conditions, but was larger and ~100 ms longer in duration with more response options. Further, the onset of the motor-related lateralized readiness potential (LRP) was earlier for the two vs. four response sets, indicating that smaller response sets enabled faster motor response preparation. The late positive complex (LPC) was present in all conditions except the two-response Stroop task, suggesting this late conflict related activity is not specifically related to task type or response-mapping complexity. Importantly, across tasks and conditions, the LRP onset at or before the conflict-related N(inc), indicating that motor preparation is a rapid, automatic process that interacts with the conflict-detection processes after it has begun. Together, these data highlight how different conflict-related processes operate in parallel and depend on both the cognitive demands of the task and the number of response options. PMID- 26827918 TI - Characterization of basic amino acids-conjugated PAMAM dendrimers as gene carriers for human adipose-derived mesenchymal stem cells. AB - Since mesenchymal stem cells (MSCs) can self-renew and differentiate into multiple cell types, the delivery of genes to this type of cell can be an important tool in the emerging field of tissue regeneration and engineering. However, development of more efficient and safe nonviral vectors for gene delivery to stem cells in particular still remains a great challenge. In this study, we describe a group of nonviral gene delivery vectors, conjugated PAMAM derivatives (PAMAM-H-R, PAMAM-H-K, and PAMAM-H-O), displaying affinity toward human adipose-derived mesenchymal stem cells (AD-MSCs). Transfection efficiency using pDNA encoding for luciferase (Luc) and enhanced green fluorescent protein (EGFP), and cytotoxicity assays were performed in human AD-MSCs. The results show that transfection efficiencies of conjugated PAMAM derivatives are improved significantly compared to native PAMAM dendrimer, and that among PAMAM derivatives, cytotoxicity of PAMAM-H-K and PAMAM-H-O were very low. Also, treatment of human AD-MSCs to polyplex formation in conjugated PAMAM derivatives, their cellular uptake and localization were analyzed by flow cytometry and confocal microscopy. PMID- 26827912 TI - Engineering broadly neutralizing antibodies for HIV prevention and therapy. AB - A combination of advances spanning from isolation to delivery of potent HIV specific antibodies has begun to revolutionize understandings of antibody mediated antiviral activity. As a result, the set of broadly neutralizing and highly protective antibodies has grown in number, diversity, potency, and breadth of viral recognition and neutralization. These antibodies are now being further enhanced by rational engineering of their anti-HIV activities and coupled to cutting edge gene delivery and strategies to optimize their pharmacokinetics and biodistribution. As a result, the prospects for clinical use of HIV-specific antibodies to treat, clear, and prevent HIV infection are gaining momentum. Here we discuss the diverse methods whereby antibodies are being optimized for neutralization potency and breadth, biodistribution, pharmacokinetics, and effector function with the aim of revolutionizing HIV treatment and prevention options. PMID- 26827920 TI - Carbon nanotubes from synthesis to in vivo biomedical applications. AB - Owing to their unique and interesting properties, extensive research round the globe has been carried out on carbon nanotubes and carbon nanotubes based systems to investigate their practical usefulness in biomedical applications. The results from these studies demonstrate a great promise in their use in targeted drug delivery systems, diagnostic techniques and in bio-analytical applications. Although, carbon nanotubes possess quite interesting properties, which make them potential candidates in the biomedical science, but they also have some inherent properties which arise great concern regarding their biosafety. In this comprehensive review, we have discussed different aspects of carbon nanotubes and carbon nanotube based systems related to biomedical applications. In the beginning, a short historical account of these tiny yet powerful particles is given followed by discussion regarding their types, properties, methods of synthesis, large scale production method, purification techniques and characterization aspects of carbon nanotubes. In the second part of the review, the functionalization of carbon nanotubes is reviewed in detail, which is not only important to make them biocompatible and stable in biological systems but also render them a great property of loading various biomolecules, diagnostic and therapeutic moieties resulting in diversified applications. In the final part of the review, emphasis is given on the pharmacokinetic aspects of carbon nanotubes including administration routes, absorption mechanisms, distribution and elimination of carbon nanotubes based systems. Lastly, a comprehensive account about the potential biomedical applications has been given followed by insights into the future. PMID- 26827919 TI - All natural cellulose acetate-Lemongrass essential oil antimicrobial nanocapsules. AB - Nanocapsules and nanoparticles play an essential role in the delivery of pharmaceutical agents in modern era, since they can be delivered in specific tissues and cells. Natural polymers, such as cellulose acetate, are becoming very important due to their availability, biocompatibility, absence of toxicity and biodegradability. In parallel, essential oils are having continuous growth in biomedical applications due to the inherent active compounds that they contain. A characteristic example is lemongrass oil that has exceptional antimicrobial properties. In this work, nanocapsules of cellulose acetate with lemongrass oil were developed with the solvent/anti-solvent method with resulting diameter tailored between 95 and 185nm. Various physico-chemical and surface analysis techniques were employed to investigate the formation of the nanocapsules. These all-natural nanocapsules found to well bioadhere to mucous membranes and to have very good antimicrobial properties at little concentrations against Escherichia coli and Staphylococcus aureus. PMID- 26827921 TI - Copper(II) oxide nanoparticles augment antifilarial activity of Albendazole: In vitro synergistic apoptotic impact against filarial parasite Setaria cervi. AB - Mass treatment of lymphatic filariasis with Albendazole (ABZ), a therapeutic benzimidazole, is fraught with serious limitations such as possible drug resistance and poor macrofilaricidal activity. Therefore, we need to develop new ABZ-based formulations to improve its antifilarial effectiveness. CuO nanoparticles were used as an adjuvant with ABZ to form ABZ-CuO nanocomposite, which was characterized by UV-vis spectroscopy, FT-IR, AFM and SEM. Antifilarial activity of nanocomposite was evaluated using relative motility assay and dye exclusion test in dark and under UV light. ROS generation, antioxidant levels, lipid peroxidation and DNA fragmentation in nanocomposite treated parasites were estimated. Biophysical techniques were employed to ascertain the mode of binding of nanocomposite to parasitic DNA. Nanocomposite increases parasite mortality as compared to ABZ in dark, and its antifilarial effect was increased further under UV light. Elevated ROS production and decline of parasitic-GST and GSH levels were observed in nanocomposite treated worms in dark, and these effects were pronounced further under UV light. Nanocomposite leads to higher DNA fragmentation as compared to ABZ alone. Further, we found that nanocomposite binds parasitic DNA in an intercalative manner where it generates ROS to induce DNA damage. Thus, oxidative stress production due to ROS generation and consequent DNA fragmentation leads to apoptosis in worms. This is the first report supporting CuO nanoparticles as a potential adjuvant with ABZ against filariasis along with enhanced antifilarial activity of nanocomposite under UV light. These findings, thus, indicate that development of ABZ-loaded nanoparticle compounds may serve as promising leads for filariasis treatment. PMID- 26827923 TI - A method for grindability testing using the Scirocco disperser. AB - In the early stages of development of a new Active Pharmaceutical Ingredient (API), insufficient material quantity is available for addressing processing issues, and it is highly desirable to be able to assess processability issues using the smallest possible powder sample quantity. A good example is milling of new active pharmaceutical ingredients. For particle breakage that is sensitive to strain rate, impact testing is the most appropriate method. However, there is no commercially available single particle impact tester for fine particulate solids. In contrast, dry powder dispersers, such as the Scirocco disperser of the Malvern Mastersizer 2000, are widely available, and can be used for this purpose, provided particle impact velocity is known. However, the distance within which the particles can accelerate before impacting on the bend is very short and different particle sizes accelerate to different velocities before impact. As the breakage is proportional to the square of impact velocity, the interpretation of breakage data is not straightforward and requires an analysis of particle velocity as a function of size, density and shape. We report our work using an integrated experimental and CFD modelling approach to evaluate the suitability of this device as a grindability testing device, with the particle sizing being done immediately following dispersion by laser diffraction. Aspirin, sucrose and alpha lactose monohydrate are tested using narrow sieve cuts in order to minimise variations in impact velocity. The tests are carried out at eight different air nozzle pressures. As intuitively expected, smaller particles accelerate faster and impact the wall at a higher velocity compared to the larger particles. However, for a given velocity the extent of breakage of larger particles is larger. Using a numerical simulation based on CFD, the relationship between impact velocity and particle size and density has been established assuming a spherical shape, and using one-way coupling, as the particle concentration is very low. Taking account of these dependencies, a clear unification of the change in the specific surface area as a function of particle size, density and impact velocity is observed, and the slope of the fitted line gives a measure of grindability for each material. The trend of data obtained here matches the one obtained by single particle impact testing. Hence aerodynamic dispersion of solids by the Scirocco disperser can be used to evaluate the ease of grindability of different materials. PMID- 26827922 TI - Application of general multilevel factorial design with formulation of fast disintegrating tablets containing croscaremellose sodium and Disintequick MCC-25. AB - Despite the popularity of orally fast disintegrating tablets (FDTs), their formulation can sometimes be challenging, producing tablets with either poor mechanical properties or high disintegration times. The aim of this research was to enhance the properties of FDTs produced by direct compression to have both sufficient hardness to withstand manual handling, and rapid disintegration time. General multilevel factorial design was applied to optimise and evaluate main and interaction effects of independent variables (i) disintegrant concentration, (ii) % filler (Disintequick MCC-25) to mannitol on the responses hardness, tensile strength and disintegration time. In this experiment mannitol was used as a diluent, Disintequick MCC-25 (to best of our knowledge there is no publication available yet for its use with FDTs) was termed in this study as a filler and croscaremellose sodium was used as the superdisintegrant. Seven formulations were prepared following a progressive two-stage approach. Each stage involved the change in the ratio of excipients (Mannitol:Filler) (1:0), (1:0.25), (1:0.50), (1:1), (0.50:1), (0.25:1), (0:1) w/w and concentration of superdisintegrant (1%, 3%, 5%, 7%, 10% w/w). All FDTs were tested for different parameters such as diameter, hardness, tensile strength, thickness, friability and disintegration time. The results of multiple linear regression analysis show a good degree of correlation between experimental (R(2):0.84, 0.94, 0.91) and predicted response (R(2):0.83, 0.96, 0.95) for hardness, tensile strength and disintegration time respectively. The optimum formulations (regarding disintegration time with acceptable hardness and friability properties) consisted of: (i) 5% w/w disintegrant and 20% w/w filler to mannitol, showing a disintegration time of 30s, a hardness of 66.6N (6.8 kg/cm(2)) and friability of 2.2%; (ii) 7% or 10% w/w disintegrant with 33.33% w/w filler to mannitol, showing disintegration time of 84 s (for 7% disintegrant) and 107 s (for 10% disintegrant), hardness of 73.86N (for 7% disintegrant) and 72.68N (for 10% disintegrant) and friability of 1.44 (for 7% disintegrant) and 1.15% (for 10% disintegrant). PMID- 26827924 TI - The cellular internalization of liposome encapsulated protoporphyrin IX by HeLa cells. AB - The proper lipid composition of liposomes designed to carry drugs determines their surface properties ensuring their accumulation within selected tissue. The electrostatic potential and surface topology of liposomes affect the internalization by single cells. The high-resolution imaging of cancer cells and the distribution of protoporphyrin-loaded liposomes within the cytoplasm and its dependence on the liposome surface properties are presented. In the paper, HeLa cells were used to investigate the uptake of porphyrin-loaded liposomes and liposomes alone by means of confocal and differential interference contrast microscopies. The effect of liposomes surface electrostatic potential and surface topology on their intracellular distribution was evaluated. The time evolution of the intracellular distribution of liposomes labelled with Rhodamine-PE was examined on HeLa cells. These studies allow for the identification of the liposome lipid composition so the efficient delivery of the active substance to cancer cells will be achieved. The obtained results showed that neutral PC liposomes are the most efficiently internalized by HeLa cells. Moreover, results showed that properties of liposomes affect not only the internalization efficiency of the photosensitizer but also its distribution within the cells, as revealed by colocalization measurements. PMID- 26827925 TI - In search of the mutual relationship between the structure, solid-state spectroscopy and molecular dynamics in selected calcium channel blockers. AB - Three isostructural 1,4-dihydropyridines (DHPs), namely, nifedipine, nitrendipine and nimodipine were selected to characterize their structure, intermolecular interactions and molecular dynamics. The studied samples were analyzed using powder X-ray diffraction (XRD), neutron (INS) and infrared spectroscopy (FT-IR) as well as solid-state nuclear magnetic resonance (NMR), where each technique was supported by the state-of-the-art theoretical calculations for solid-state. By combining multiple experimental techniques with advanced theoretical calculations we were able to shed light on the mutual relation between the structure, stabilizing intermolecular interactions and their spectral response. For the first time, unambiguous computationally-supported assignment of the most prominent spectral features in DHPs is presented to give a valuable support for polymorph screening and drug control. Molecular motions were interpreted in details, revealing that a dynamic reservoir of each compound is dominated by intra-molecular reorientations of methyl groups and large-amplitude oscillations in terminal chains. Our study successfully validates the realm of applicability of first-principles solid-state calculations in search of the mutual relation between the structure and spectroscopy in this important class of drugs. Such approach gives a first necessary step to gather combined structure-dynamics data on functionalized DHPs, which are of importance to better understand crystallization and binding tendency. The NMR relaxation experiments reveal that nitro groups significantly hinder the reorientation of methyl rotors and provide the first evidence of low-temperature methyl-group tunneling in DHPs, an intriguing quantum-effect which is to be further explored. PMID- 26827926 TI - Insights into the subunit arrangement and diversity of paradoxin and taipoxin. AB - Paradoxin and taipoxin are neurotoxic phospholipases from the inland and coastal species of Australian taipan. Despite their relatively high sequence homology of 70% and 84% for the acidic and basic chains respectively, they differ substantially in reported assays of neurotoxicity. This study provides the first characterisation of paradoxin, which like taipoxin, is a trimer at physiological pH. More broadly, these toxins were found to be composed of a more diverse range of subunits than previously recognised, including newly discovered gammaTPx isoforms, which give rise to an additional, major conformation of TPx. PMID- 26827927 TI - Psychrobacter glaciei sp. nov., isolated from the ice core of an Arctic glacier. AB - A Gram-stain-negative, non-motile, non-spore-forming, non-pigmented, oxidase- and catalase-positive bacterial strain, designated BIc20019T, was isolated from the ice core of Austre Lovenbreen in Ny-Alesund, Svalbard. The temperature and NaCl ranges for growth were 4-34 degrees C (optimum, 25-29 degrees C) and 0-8% (w/v) (optimum, 2-4%). Analysis of the 16S rRNA gene sequence indicated that strain BIc20019T belonged to the genus Psychrobacter and was closely related to Psychrobacter arcticus 273-4T, Psychrobacter cryohalolentis K5T, 'Psychrobacter fjordensis' BSw21516B, Psychrobacter fozii LMG 21280T, Psychrobacter luti LMG 21276T and Pyschrobacter okhotskensis MD17T at greater than 99% similarity. Phylogenetic analysis based on gyrB gene sequences revealed highest similarity (93.6%) to P. okhotskensis MD17T. However, DNA hybridization experiments revealed a low level of DNA-DNA relatedness (<59%) between strain BIc20019T and its closest relatives. Strain BIc20019T contained ubiquinone-8 (Q-8) as the predominant respiratory quinone, and C18:1omega9c and summed feature 3 (C16:1omega7c and/or iso-C15:0 2-OH) as the major fatty acids. It had a DNA G+C content of 46.3 mol%. The polar lipid profile of strain BIc20019T was mainly composed of phosphatidylglycerol, phosphatidylethanolamine and diphosphatidylglycerol. Owing to the differences in phenotypic and chemotaxonomic characteristics, phylogenetic analysis based on 16S rRNA gene and gyrB gene sequences, and DNA-DNA relatedness data, the isolate merits classification within a novel species for which the name Psychrobacter glaciei sp. nov. is proposed. The type strain is BIc20019T (=KCTC 42280T = CCTCC AB 2014019T). PMID- 26827928 TI - Papiliotrema leoncinii sp. nov. and Papiliotrema miconiae sp. nov., two tremellaceous yeast species from Brazil. AB - Two yeast species, Papiliotrema leoncinii sp. nov. and Papiliotrema miconiae sp. nov., in the family Rhynchogastremataceae of the Tremellales are proposed. The two species are related to six species of the genus Papiliotrema: Papiliotrema aureus, P. flavescens, P. terrestris, P. baii, P. ruineniae and P. wisconsinensis. The novel species are proposed on the basis of the sequence-based phylogenetic species concept with analysis of the D1/D2 region of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) region. A total of 16 strains of Papiliotrema leoncinii sp. nov. were obtained from freshwater and bromeliad leaves collected in Brazil. Papiliotrema leoncinii sp. nov. differs by 11, 12, 16, 14, 11 and 13 substitutions in the D1/D2 domain from the related species P. aureus, P. flavescens, P. terrestris, P. baii, P. ruineniae and P. wisconsinensis, respectively. Differences of 11 substitutions and 21 or more substitutions in ITS regions were found when the sequences of Papiliotrema leoncinii sp. nov. were compared with P. wisconsinensis and its closest relatives. The type strain of Papiliotrema leoncinii sp. nov. is UFMG-CM-Y374T (=CBS 13918T). Papiliotrema miconiae sp. nov. is represented by two strains isolated from a flower of Miconia sp. and a water sample in Brazil. Papiliotrema miconiae sp. nov. differs from the related species P. aureus and P. ruineniae by eight substitutions, from P. flavescens and P. terrestris by 11 substitutions, from P. baii by 10 substitutions and from P. wisconsinensis by 6 substitutions in the D1/D2 domain, and by 7 substitutions from P. wisconsinensis and more than 19 substitutions in the ITS region from its closest relatives. The type strain of Papiliotrema miconiae sp. nov. is CBS 8358T (ML 3666T=DBVPG-4492T). The MycoBank numbers for Papiliotrema leoncinii sp. nov. and Papiliotrema miconiae sp. nov. are MB 813594 and MB 814882, respectively. PMID- 26827929 TI - Modulation of the host transcriptome by Coxiella burnetii nuclear effector Cbu1314. AB - Coxiella burnetii is a Gram-negative, obligate intracellular pathogen that directs the formation of a parasitophorous vacuole derived from the host lysosomal network. Biogenesis and maintenance of this replicative compartment is dependent on bacterial protein synthesis and results in differential expression of specific host genes. However, the mechanisms by which the pathogen induces changes in the host transcriptome is poorly understood. In the current study we identified a Dot/Icm secreted effector, Cbu1314, which encodes two nuclear localization signals that are required for nuclear localization and association with host chromatin. Chromatin immunoprecipitation (ChIP) and deep sequencing revealed that Cbu1314 associated with host genes involved in transcription, cell signaling, and the immune response. RNA sequencing of cells overexpressing Cbu1314 demonstrated that Cbu1314 modulates the host transcriptome and these transcriptional changes required a functional nuclear localization signal. Of the differentially expressed genes, sixteen were also identified as Cbu1314 targets using ChIP sequencing. Collectively these results suggest that Cbu1314 associates with host chromatin and plays a role in modulating the host transcriptome. PMID- 26827930 TI - A new variant of rabbit hemorrhagic disease virus G2-like strain isolated in China. AB - To investigate the genetic variability and evolution of rabbit hemorrhagic disease virus (RHDV) strains in China, VP60 gene sequences of eight new isolates collected from farms with RHD occurrences in China between 2009 and 2014 were analyzed, and compared with the reference sequence of the vaccine strain WF/China/2007. We conducted a comprehensive analysis of the Chinese RHDV strains, including hemagglutination tests, western blot and immunosassays of capsid proteins, and phylogenetic analysis, and identified a new distinct antigenic variant. Specifically, strain HB/2014 collected in North China was identified as a non-hemagglutinating strain, and belongs to the original RHDV (G1-G5) group. The other seven isolates were classified in genogroup G6 (RHDVa), which was widely distributed across China before 2014, and was thought to replace the earlier groups. Antigenic characterization of the VP60 genes revealed a large degree of nucleotide sequence divergence between HB/2014 and the other Chinese strains. However, the current vaccine showed complete cross-protection against HB/2014 challenge in inoculated rabbits. Collectively, these data provide new tools and insight for further understanding the molecular evolution of RHDV in China. PMID- 26827932 TI - Impulsivity, decreased social exploration, and executive dysfunction in a mouse model of frontotemporal dementia. AB - Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder, a major subset of which is characterized by the accumulation of abnormal forms of the protein tau, leading to impairments in motor functions as well as language and behavioral alterations. Tau58-2/B mice express human tau with the P301S mutation found in familial forms of FTLD in neurons. By assessing three age cohorts of Tau58-2/B mice in a comprehensive behavioral test battery, we found that the tauopathy animals showed age-dependent signs of impulsivity, decreased social exploration and executive dysfunction. The deficit in executive function was first limited to decreased spatial working memory, but with aging this was extended to impaired instrumental short-term memory. Tau pathology was prominent in brain regions underlying these behaviors. Thus, Tau-58-2/B mice recapitulate neurological deficits of the behavioral variant of frontotemporal dementia (bvFTD), presenting them as a suitable model to test therapeutic interventions for the amelioration of this variant. PMID- 26827931 TI - A genomics-based framework for identifying biomarkers of human neurodevelopmental toxicity. AB - Human embryonic stem cell (hESC) neural differentiation models have tremendous potential for evaluating environmental compounds in terms of their ability to induce neurodevelopmental toxicity. Genomic based-approaches are being applied to identify changes underlying normal human development (in vitro and in vivo) and the effects of environmental exposures. Here, we investigated whether mechanisms that are shared between hESC neural differentiation model systems and human embryos are candidate biomarkers of developmental toxicities for neurogenesis. We conducted a meta-analysis of transcriptomic datasets with the goal of identifying differentially expressed genes that were common to the hESC-model and human embryos. The overlapping NeuroDevelopmental Biomarker (NDB) gene set contained 304 genes which were enriched for their roles in neurogenesis. These genes were investigated for their utility as candidate biomarkers in the context of toxicogenomic studies focused on the effects of retinoic acid, valproic acid, or carbamazepine in hESC models of neurodifferentiation. The results revealed genes, including 13 common targets of the 3 compounds, that were candidate biomarkers of neurotoxicity in hESC-based studies of environmental toxicants. PMID- 26827933 TI - Laser desorption/ionization mass spectrometry of lipids using etched silver substrates. AB - Silver-assisted laser desorption/ionization mass spectrometry can be used for the analysis of small molecules. For example, adduct formation with silver cations enables the molecular analysis of long-chain hydrocarbons, which are difficult to ionize via conventional matrix-assisted laser desorption ionization (MALDI). Here we used highly porous silver foils, produced by etching with nitric acid, as sample substrates for LDI mass spectrometry. As model system for the analysis of complex lipid mixtures, cuticular extracts of fruit flies (Drosophila melanogaster) and worker bees (Apis mellifera) were investigated. The mass spectra obtained by spotting extract onto the etched silver substrates demonstrate the sensitive detection of numerous lipid classes such as long-chain saturated and unsaturated hydrocarbons, fatty acyl alcohols, wax esters, and triacylglycerols. MS imaging of cuticular surfaces with a lateral resolution of a few tens of micrometers became possible after blotting, i.e., after transferring lipids by physical contact with the substrate. The examples of pheromone producing male hindwings of the squinting bush brown butterfly (Bicyclus anynana) and a fingermark are shown. Because the substrates are also easy to produce, they provide a viable alternative to colloidal silver nanoparticles and other so far described silver substrates. PMID- 26827934 TI - Investigation and optimization of parameters affecting the multiply charged ion yield in AP-MALDI MS. AB - Liquid matrix-assisted laser desorption/ionization (MALDI) allows the generation of predominantly multiply charged ions in atmospheric pressure (AP) MALDI ion sources for mass spectrometry (MS) analysis. The charge state distribution of the generated ions and the efficiency of the ion source in generating such ions crucially depend on the desolvation regime of the MALDI plume after desorption in the AP-to-vacuum inlet. Both high temperature and a flow regime with increased residence time of the desorbed plume in the desolvation region promote the generation of multiply charged ions. Without such measures the application of an electric ion extraction field significantly increases the ion signal intensity of singly charged species while the detection of multiply charged species is less dependent on the extraction field. In general, optimization of high temperature application facilitates the predominant formation and detection of multiply charged compared to singly charged ion species. In this study an experimental set up and optimization strategy is described for liquid AP-MALDI MS which improves the ionization efficiency of selected ion species up to 14 times. In combination with ion mobility separation, the method allows the detection of multiply charged peptide and protein ions for analyte solution concentrations as low as 2fmol/MUL (0.5MUL, i.e. 1fmol, deposited on the target) with very low sample consumption in the low nL-range. PMID- 26827938 TI - Excitation energy transfer between Light-harvesting complex II and Photosystem I in reconstituted membranes. AB - Light-harvesting complex II (LHCII), the major peripheral antenna of Photosystem II in plants, participates in several concerted mechanisms for regulation of the excitation energy and electron fluxes in thylakoid membranes. In part, these include interaction of LHCII with Photosystem I (PSI) enhancing the latter's absorption cross-section - for example in the well-known state 1 - state 2 transitions or as a long-term acclimation to high light. In this work we examined the capability of LHCII to deliver excitations to PSI in reconstituted membranes in vitro. Proteoliposomes with native plant thylakoid membrane lipids and different stoichiometric ratios of LHCII:PSI were reconstituted and studied by steady-state and time-resolved fluorescence spectroscopy. Fluorescence emission from LHCII was strongly decreased in PSI-LHCII membranes due to trapping of excitations by PSI. Kinetic modelling of the time-resolved fluorescence data revealed the existence of separate pools of LHCII distinguished by the time scale of energy transfer. A strongly coupled pool, equivalent to one LHCII trimer per PSI, transferred excitations to PSI with near-unity efficiency on a time scale of less than 10ps but extra LHCIIs also contributed significantly to the effective antenna size of PSI, which could be increased by up to 47% in membranes containing 3 LHCII trimers per PSI. The results demonstrate a remarkable competence of LHCII to increase the absorption cross-section of PSI, given the opportunity that the two types of complexes interact in the membrane. PMID- 26827935 TI - Fixed and live visualization of RNAs in Drosophila oocytes and embryos. AB - The ability to visualize RNA in situ is essential to dissect mechanisms for the temporal and spatial regulation of gene expression that drives development. Although considerable attention has been focused on transcriptional control, studies in model organisms like Drosophila have highlighted the importance of post-transcriptional mechanisms - most notably intracellular mRNA localization - in the formation and patterning of the body axes, specification of cell fates, and polarized cell functions. Our understanding of both types of regulation has been greatly advanced by technological innovations that enable a combination of highly quantitative and dynamic analysis of RNA. This review presents two methods, single molecule fluorescence in situ hybridization for high resolution quantitative RNA detection in fixed Drosophila oocytes and embryos and genetically encoded fluorescent RNA labeling for detection in live cells. PMID- 26827939 TI - Mechanism of inhibition of NiFe hydrogenase by nitric oxide. AB - Hydrogenases reversibly catalyze the oxidation of molecular hydrogen and are inhibited by several small molecules including O2, CO and NO. In the present work, we investigate the mechanism of inhibition by NO of the oxygen-sensitive NiFe hydrogenase from Desulfovibrio fructosovorans by coupling site-directed mutagenesis, protein film voltammetry (PFV) and EPR spectroscopy. We show that micromolar NO strongly inhibits NiFe hydrogenase and that the mechanism of inhibition is complex, with NO targeting several metallic sites in the protein. NO reacts readily at the NiFe active site according to a two-step mechanism. The first and faster step is the reversible binding of NO to the active site followed by a slower and irreversible transformation at the active site. NO also induces irreversible damage of the iron-sulfur centers chain. We give direct evidence of preferential nitrosylation of the medial [3Fe-4S] to form dinitrosyl-iron complexes. PMID- 26827940 TI - BCL-2 family proteins as regulators of mitochondria metabolism. AB - The BCL-2 family proteins are major regulators of apoptosis, and one of their major sites of action are the mitochondria. Mitochondria are the cellular hubs for metabolism and indeed selected BCL-2 family proteins also possess roles related to mitochondria metabolism and dynamics. Here we discuss the link between mitochondrial metabolism/dynamics and the fate of stem cells, with an emphasis on the role of the BID-MTCH2 pair in regulating this link. We also discuss the possibility that BCL-2 family proteins act as metabolic sensors/messengers coming on and off of mitochondria to "sample" the cytosol and provide the mitochondria with up-to-date metabolic information. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. PMID- 26827941 TI - Resveratrol inhibits inflammatory signaling implicated in ionizing radiation induced premature ovarian failure through antagonistic crosstalk between silencing information regulator 1 (SIRT1) and poly(ADP-ribose) polymerase 1 (PARP 1). AB - This study hypothesized that resveratrol, a silencing information regulator 1 (SIRT1) activator, would counteract the inflammatory signaling associated with radiotherapy-induced premature ovarian failure (POF). Immature female Sprague Dawley rats were subjected to a single dose of gamma-radiation to induce POF and treated with resveratrol (25mg/kg) once daily for two weeks before and three days post irradiation. Resveratrol preserves the entire ovarian follicle pool manifested by increasing serum anti-Mullerian hormone (AMH) levels. Radiation triggered inflammatory process in the ovary through enhanced NF-kappaB and poly(ADP-ribose) polymerase (PARP)-1 expression which convinced the expression of inflammatory markers including IL-6, IL-8, and visfatin mRNA levels, as well as inducible nitric oxide synthase and cyclooxygenase-2 protein expression with a concomitant reduction in IL-10 mRNA levels. Resveratrol significantly counteracted the effect of radiation and upregulated the gene expression of peroxisome proliferator-activated receptor gamma (PPAR-gamma) and SIRT1. Resveratrol-activated SIRT1 expression was associated with inhibition of PARP-1 and NF-kappaB expression-mediated inflammatory cytokines. Our findings suggest that resveratrol restored ovarian function through increasing AMH levels, and diminishing ovarian inflammation, predominantly via upregulation of PPAR-gamma and SIRT1 expression leading to inhibition of NF-kappaB provoked inflammatory cytokines. PMID- 26827944 TI - Different contexts, different pains, different experiences. AB - Pain is an ambiguous perception: the same pain stimulation can be perceived differently in different contexts, producing different experiences, ranging from mild to unbearable pain. It can be even experienced as a rewarding sensation within the appropriate context. Overall, placebo and nocebo effects appear to be very good models to understand how the psychosocial context modulates the experience of pain. In this review, we examine the effects of different contexts on pain, with a specific focus on the neurobiological mechanisms. Positive and rewarding contexts inform the patients that an effective treatment is being delivered and are capable of producing pain relief through the activation of specific systems such as opioids, cannabinoids and dopamine. Conversely, a negative context can produce pain exacerbation and clinical worsening through the modulation of different systems, such as the activation of cholecystokinin and the deactivation of opioids and dopamine. In addition, when a therapy is delivered unbeknownst to the patient, its effects are reduced. A better understanding of the neurobiological underpinnings of the context-pain interaction is a challenge both for future pain research and for good clinical practice. PMID- 26827943 TI - Prenylated quinolinecarboxylic acid derivative suppresses immune response through inhibition of PAK2. AB - Development of new immunosuppressing agents is necessary in organ transplantation or immune diseases. Because Ppc-1 exhibits a suppressing effect on interleukin-2 (IL2) production in Jurkat cells, we synthesized and screened Ppc-1 derivatives that preserve prenylated quinolinecarboxylic acid (PQA) structure, and identified compound 18 (PQA-18) as a novel molecule with immunosuppressing effect. PQA-18 suppressed not only IL2 but also IL4, IL6, and tumor necrosis factor-alpha production in human peripheral lymphocytes without affecting cell viability. Two dimensional gel electrophoresis analysis and in vitro kinase assay revealed that PQA-18 inhibits kinase activity of p21-activated kinase 2 (PAK2). Administration of PQA-18 by intraperitoneal injection suppressed the population of a subset of regulatory T cells and the immunoglobulin (Ig) production against T cell dependent antigens in mice. Treatment with the PQA-18 ointment on Nc/Nga mice, a model of human atopic dermatitis, improved skin lesions and serum IgE levels. These results suggest that PQA-18 is a unique PAK2 inhibitor with potent immunosuppressing effects in vitro and in vivo. PQA-18 may be a valuable lead for the development of novel immunosuppressants. PMID- 26827942 TI - Free-fatty acid receptor-4 (GPR120): Cellular and molecular function and its role in metabolic disorders. AB - Over the last decade, a subfamily of G protein-coupled receptors that are agonized by endogenous and dietary free-fatty acids (FFA) has been discovered. These free-fatty acid receptors include FFA2 and FFA3, which are agonized by short-chained FFA, as well as FFA1 and FFA4, which are agonized by medium-to-long chained FFA. Ligands for FFA1 and FFA4 comprise the family of long chain polyunsaturated omega-3 fatty acids including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), suggesting that many of the long-known beneficial effects of these fats may be receptor mediated. In this regard, FFA4 has gathered considerable interest due to its role in ameliorating inflammation, promoting insulin sensitization, and regulating energy metabolism in response to FFA ligands. The goal of this review is to summarize the body of evidence in regard to FFA4 signal transduction, its mechanisms of regulation, and its functional role in a variety of tissues. In addition, recent endeavors toward discovery of small molecules that modulate FFA4 activity are also presented. PMID- 26827945 TI - The role of autophagy in modulation of neuroinflammation in microglia. AB - Microglia have multiple functions in regulating homeostasis in the central nervous system (CNS), and microglial inflammation is thought to play a role in the etiology of the neurodegenerative diseases. When endogenous or exogenous stimuli trigger disorders in microenvironmental homeostasis in CNS, microglia critically determine the fate of other neural cells. Recently, it was reported that autophagy might influence inflammation and activation of microglia. Though the interaction between autophagy and macrophages has been reported and reviewed in length, the role of autophagy in microglia has yet to be reviewed. Herein, we will highlight recent advances on the emerging role of autophagy in microglia, focusing on the regulation of autophagy during microglial inflammation, and the possible mechanism involved. PMID- 26827946 TI - Vitamin D: Historical Overview. AB - A history of vitamin D has been provided, dating from the earliest description of rickets, the disease resulting from vitamin D deficiency, to a current understanding of vitamin D metabolism and the mechanism of action of its hormonal form in regulating gene expression in target organs. Vitamin D is produced in skin by impact of 280-310 nm light on 7-dehydrocholesterol. The vitamin D is then converted in the liver to a circulating form, 25-hydroxyvitamin D that is converted largely, if not exclusively, in the kidney to the final hormone, 1alpha,25-dihydroxyvitamin D. This hormone functions through a nuclear receptor that regulates expression of key genes in target organs. Among its many resulting functions are increased intestinal calcium and phosphate absorption, bone calcium mobilization, and renal reabsorption of calcium. The resultant increase in serum calcium and phosphate supports bone mineralization, curing rickets, and osteomalacia. There are many other functions of vitamin D that remain to be described that contribute to its health supporting role. PMID- 26827947 TI - Genomic Determinants of Vitamin D-Regulated Gene Expression. AB - Insight into mechanisms that link the actions of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to the regulation of gene expression has evolved extensively since the initial discovery of a nuclear protein known as the vitamin D receptor (VDR). Perhaps most important was the molecular cloning of this receptor which enabled its inclusion within the nuclear receptor gene family and further studies of both its structure and regulatory function. Current studies are now refocused on the vitamin D hormone's action at the genome, where VDR together with other transcription factors coordinates the recruitment of chromatin active coregulatory complexes that participate directly in the modification of gene output. These studies highlight the role of chromatin in the expression of genes and the dynamic impact of the epigenetic landscape that contextualizes individual gene loci thus influencing the VDR's transcriptional actions. In this chapter, we summarize advances made over the past few years in understanding vitamin D action on a genome-wide scale, focusing on overarching principles that have emerged at this level. Of particular significance is the finding that dynamic changes that occur to the genome during cellular differentiation at both genetic and epigenetic levels profoundly alter the ability of 1,25(OH)2D3 and its receptor to regulate gene expression. We address the broad impact of differentiation on specific epigenetic histone modifications that occur across the genome and the ability of the VDR to influence this activity at selected gene loci as well. These studies advance our understanding of not only vitamin D action but also of the complex and dynamic role played by the genome itself as a major determinant of VDR activity. PMID- 26827949 TI - Structural Studies of Vitamin D Nuclear Receptor Ligand-Binding Properties. AB - The vitamin D nuclear receptor (VDR) and its natural ligand, 1alpha,25 dihydroxyvitamin D3 hormone (1,25(OH)2D3, or calcitriol), classically regulate mineral homeostasis and metabolism but also much broader range of biological functions, such as cell growth, differentiation, antiproliferation, apoptosis, adaptive/innate immune responses. Being widely expressed in various tissues, VDR represents an important therapeutic target in the treatment of diverse disorders. Since ligand binding is a key step in VDR-mediated signaling, numerous 1,25(OH)2D3 analogs have been synthesized in order to selectively modulate the receptor activity. Most of the synthetic analogs have been developed by modification of a parental compound and some of them mimic 1,25(OH)2D3 scaffold without being structurally related to it. The ability of ligands that have different size and conformation to bind to VDR and to demonstrate biological effects is intriguing, and therefore, ligand-binding properties of the receptor have been extensively investigated using a variety of biochemical, biophysical, and computational methods. In this chapter, we describe different aspects of the structure-function relationship of VDR in complex with natural and synthetic ligands coming from structural analysis. With the emphasis on the binding modes of the most promising compounds, such as secosteroidal agonists and 1,25(OH)2D3 mimics, we also highlight the action of VDR antagonists and the evidence for the existence of an alternative ligand-binding site within the receptor. Additionally, we describe the crystal structures of VDR mutants associated with hereditary vitamin D-resistant rickets that display impaired ligand-binding function. PMID- 26827950 TI - Crystal Structure of the Vitamin D Receptor Ligand-Binding Domain with Lithocholic Acids. AB - The secondary bile acid lithocholic acid (LCA) and its derivatives act as selective modulators of the vitamin D receptor (VDR), although their structures fundamentally differ from that of the natural hormone 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). The complexes of the ligand-binding domain of rat VDR (VDR-LBD) with LCA and its derivatives revealed that the ligands bound to the same ligand binding pocket (LBP) of VDR-LBD that 1,25(OH)2D3 binds to, but in the opposite orientation; their A-ring was positioned at the top of the LBP, whereas their acyclic tail was located at the bottom of the LBP. However, most of the hydrophobic and hydrophilic interactions observed in the complex with 1,25(OH)2D3 were reproduced in the complexes with LCA and its derivatives. Additional interactions between VDR-LBD and the C-3 substituents of the A-ring were also observed in the complexes, probably related to the observed difference in the potency among the LCA-type ligands. Recently, zebrafish VDR has been reported to have the second LBP on the outside of the canonical LBP, although its physiological function is unclear. PMID- 26827952 TI - Analogs of 1alpha,25-Dihydroxyvitamin D3 in Clinical Use. AB - Biologically active metabolites of vitamin D that have been successfully developed for the clinical market are described. Their properties that resulted in their success in the clinic are also provided. Precursors of the metabolically active 1alpha,25-dihydroxyvitamin D have been prepared and successfully marketed not only for renal failure patients but also for a variety of patients having metabolic bone disorders. Finally, successful analogs of 1alpha,25 dihydroxyvitamin D in use in the clinic worldwide are presented including properties that have contributed to their success. PMID- 26827948 TI - Inhibitors for the Vitamin D Receptor-Coregulator Interaction. AB - The vitamin D receptor (VDR) belongs to the superfamily of nuclear receptors and is activated by the endogenous ligand 1,25-dihydroxyvitamin D3. The genomic effects mediated by VDR consist of the activation and repression of gene transcription, which includes the formation of multiprotein complexes with coregulator proteins. Coregulators bind many nuclear receptors and can be categorized according to their role as coactivators (gene activation) or corepressors (gene repression). Herein, different approaches to develop compounds that modulate the interaction between VDR and coregulators are summarized. This includes coregulator peptides that were identified by creating phage display libraries. Subsequent modification of these peptides including the introduction of a tether or nonhydrolyzable bonds resulted in the first direct VDR-coregulator inhibitors. Later, small molecules that inhibit VDR-coregulator inhibitors were identified using rational drug design and high-throughput screening. Early on, allosteric inhibition of VDR-coregulator interactions was achieved with VDR antagonists that change the conformation of VDR and modulate the interactions with coregulators. A detailed discussion of their dual agonist/antagonist effects is given as well as a summary of their biological effects in cell-based assays and in vivo studies. PMID- 26827951 TI - 25-Hydroxyvitamin D3 24-Hydroxylase: A Key Regulator of 1,25(OH)2D3 Catabolism and Calcium Homeostasis. AB - One of the most pronounced effects of the hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is increased synthesis of 25 hydroxyvitamin D3 24-hydroxylase (CYP24A1), the enzyme responsible for the catabolism of 1,25(OH)2D3. Thus, 1,25(OH)2D3 regulates its own metabolism, protecting against hypercalcemia and limiting the levels of 1,25(OH)2D3 in cells. This chapter summarizes the catalytic properties of CYP24A1, the recent data related to the crystal structure of CYP24A1, the findings obtained from the generation of mice deficient for the Cyp24a1 gene as well as recent data identifying a causal role of a genetic defect in CYP24A1 in certain patients with idiopathic infantile hypercalcemia. This chapter also reviews the regulation of renal and placental CYP24A1 as well as the genomic mechanisms, including coactivators, repressors, and epigenetic modification, involved in modulating 1,25(OH)2D3 regulation of CYP24A1. We conclude with future research directions related to this key regulator of 1,25(OH)2D3 catabolism and calcium homeostasis. PMID- 26827953 TI - 1,25-Dihydroxyvitamin D and Klotho: A Tale of Two Renal Hormones Coming of Age. AB - 1,25-Dihydroxyvitamin D3 (1,25D) is the renal metabolite of vitamin D that signals through binding to the nuclear vitamin D receptor (VDR). The ligand receptor complex transcriptionally regulates genes encoding factors stimulating calcium and phosphate absorption plus bone remodeling, maintaining a skeleton with reduced risk of age-related osteoporotic fractures. 1,25D/VDR signaling exerts feedback control of Ca/PO4 via regulation of FGF23, klotho, and CYP24A1 to prevent age-related, ectopic calcification, fibrosis, and associated pathologies. Vitamin D also elicits xenobiotic detoxification, oxidative stress reduction, neuroprotective functions, antimicrobial defense, immunoregulation, anti inflammatory/anticancer actions, and cardiovascular benefits. Many of the healthspan advantages conferred by 1,25D are promulgated by its induction of klotho, a renal hormone that is an anti-aging enzyme/coreceptor that protects against skin atrophy, osteopenia, hyperphosphatemia, endothelial dysfunction, cognitive defects, neurodegenerative disorders, and impaired hearing. In addition to the high-affinity 1,25D hormone, low-affinity nutritional VDR ligands including curcumin, polyunsaturated fatty acids, and anthocyanidins initiate VDR signaling, whereas the longevity principles resveratrol and SIRT1 potentiate VDR signaling. 1,25D exerts actions against neural excitotoxicity and induces serotonin mood elevation to support cognitive function and prosocial behavior. Together, 1,25D and klotho maintain the molecular signaling systems that promote growth (p21), development (Wnt), antioxidation (Nrf2/FOXO), and homeostasis (FGF23) in tissues crucial for normal physiology, while simultaneously guarding against malignancy and degeneration. Therefore, liganded-VDR modulates the expression of a "fountain of youth" array of genes, with the klotho target emerging as a major player in the facilitation of health span by delaying the chronic diseases of aging. PMID- 26827954 TI - Hedgehog and Vitamin D Signaling Pathways in Development and Disease. AB - The classic physiological activity associated with the vitamin D scaffold is the maintenance of calcium and phosphorous homeostasis in the bone. This activity is commonly attributed to direct binding of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3, calcitriol], the hormonally active form of vitamin D, to the vitamin D receptor (VDR). More recently, calcitriol and VDR have been shown to control the expression of genes associated with cellular proliferation and differentiation in a wide variety of cells, suggesting more extensive biological activities for the vitamin D system. Recently, calcitriol and several structurally related members of the vitamin D class of seco-steroids have demonstrated the ability to regulate the hedgehog (Hh) signaling pathway. Hh signaling plays an essential role with respect to tissue differentiation during embryogenesis and maintains stem cell populations in certain adult tissues. Potential mechanisms of cross talk between the two signaling pathways highlight our evolving understanding of the complexities of calcitriol/VDR signaling and suggest a cooperative role during multiple stages of human development and disease. PMID- 26827955 TI - Molecular Approaches for Optimizing Vitamin D Supplementation. AB - Vitamin D can be synthesized endogenously within UV-B exposed human skin. However, avoidance of sufficient sun exposure via predominant indoor activities, textile coverage, dark skin at higher latitude, and seasonal variations makes the intake of vitamin D fortified food or direct vitamin D supplementation necessary. Vitamin D has via its biologically most active metabolite 1alpha,25 dihydroxyvitamin D and the transcription factor vitamin D receptor a direct effect on the epigenome and transcriptome of many human tissues and cell types. Different interpretation of results from observational studies with vitamin D led to some dispute in the field on the desired optimal vitamin D level and the recommended daily supplementation. This chapter will provide background on the epigenome- and transcriptome-wide functions of vitamin D and will outline how this insight may be used for determining of the optimal vitamin D status of human individuals. These reflections will lead to the concept of a personal vitamin D index that may be a better guideline for an optimized vitamin D supplementation than population-based recommendations. PMID- 26827956 TI - The Role of Vitamin D3 in the Development and Neuroprotection of Midbrain Dopamine Neurons. AB - Vitamin D has long been synonymous with bone health. More recently, new health benefits are continually being associated with vitamin D, including a burgeoning field on neuroprotective properties. This has generated a huge explosion of interest in recent years in the potential for vitamin D to be used not only as a therapeutic in neurodegenerative disease, including Parkinson's disease, but also as biomarkers and for risk association. With an emphasis on Parkinson's disease, this chapter will discuss recent evidence supporting the assertion that vitamin D can be a useful therapeutic agent used as an intervention therapy to be combined with existing treatments; and the case for further development of novel treatments utilizing the potential of vitamin D. In addition, we present novel, previously unpublished evidence showing that in a unilateral model of Parkinson's disease, vitamin D can not only reduce the extent of denervation, but that this is also reflected in functional benefit to the animals. The potential of vitamin D is slowly being realized; in the future, it will be widely associated with far more than just bone health and may even contribute to an elusive treatment of neurodegenerative illness. PMID- 26827957 TI - Vitamin D and Cardiac Differentiation. AB - Calcitriol (1,25-dihydroxycholecalciferol or 1,25-D3) is the hormonally active metabolite of vitamin D. Experimental studies of vitamin D receptors and 1,25-D3 establish calcitriol to be a critical regulator of the structure and function of the heart. Clinical studies link vitamin D deficiency with cardiovascular disease (CVD). Emerging evidence demonstrates that calcitriol is highly involved in CVD related signaling pathways, particularly the Wnt signaling pathway. Addition of 1,25-D3 to cardiomyocyte cells and examination of its effects on cardiomyocytes and mainly Wnt11 signaling allowed the specific characterization of the role of calcitriol in cardiac differentiation. 1,25-D3 is demonstrated to: (i) inhibit cell proliferation without promoting apoptosis; (ii) decrease expression of genes related to the regulation of the cell cycle; (iii) promote formation of cardiomyotubes; (iv) induce expression of casein kinase-1-alpha1, a negative regulator of the canonical Wnt signaling pathway; and (v) increase expression of noncanonical Wnt11, which has been recognized to induce cardiac differentiation during embryonic development and in adult cells. Thus, it appears that vitamin D promotes cardiac differentiation through negative modulation of the canonical Wnt signaling pathway and upregulation of noncanonical Wnt11 expression. Future work to elucidate the role(s) of vitamin D in cardiovascular disorders will hopefully lead to improvement and potentially prevention of CVD, including abnormal cardiac differentiation in settings such as postinfarction cardiac remodeling. PMID- 26827958 TI - Vitamin D in Prostate Cancer. AB - Metastatic castration-resistant prostate cancer (mCRPC) is a progressive, noncurable disease induced by androgen receptor (AR) upon its activation by tumor tissue androgen, which is generated from adrenal steroid dehydroepiandrosterone (DHEA) through intracrine androgen biosynthesis. Inhibition of mCRPC and early stage, androgen-dependent prostate cancer by calcitriol, the bioactive vitamin D3 metabolite, is amply documented in cell culture and animal studies. However, clinical trials of calcitriol or synthetic analogs are inconclusive, although encouraging results have recently emerged from pilot studies showing efficacy of a safe-dose vitamin D3 supplementation in reducing tumor tissue inflammation and progression of low-grade prostate cancer. Vitamin D-mediated inhibition of normal and malignant prostate cells is caused by diverse mechanisms including G1/S cell cycle arrest, apoptosis, prodifferentiation gene expression changes, and suppressed angiogenesis and cell migration. Biological effects of vitamin D are mediated by altered expression of a gene network regulated by the vitamin D receptor (VDR), which is a multidomain, ligand-inducible transcription factor similar to AR and other nuclear receptors. AR-VDR cross talk modulates androgen metabolism in prostate cancer cells. Androgen inhibits vitamin D-mediated induction of CYP24A1, the calcitriol-degrading enzyme, while vitamin D promotes androgen inactivation by inducing phase I monooxygenases (e.g., CYP3A4) and phase II transferases (e.g., SULT2B1b, a DHEA-sulfotransferase). CYP3A4 and SULT2B1b levels are markedly reduced and CYP24A1 is overexpressed in advanced prostate cancer. In future trials, combining low-calcemic, potent next-generation calcitriol analogs with CYP24A1 inhibition or androgen supplementation, or cancer stem cell suppression by a phytonutrient such as sulfarophane, may prove fruitful in prostate cancer prevention and treatment. PMID- 26827959 TI - Metabolism and Action of 25-Hydroxy-19-nor-Vitamin D3 in Human Prostate Cells. AB - Since the discovery of 1alpha,25(OH)2D3 in the early 1970s, it has been widely accepted that this metabolite is responsible for the biological actions of vitamin D. Likewise, we have assumed that 25(OH)-19-nor-D3-dependent growth inhibition of human prostate PZ-HPV-7 cells was the result of its subsequent conversion to 1alpha,25(OH)2-19-nor-D3, catalyzed by CYP27B1 within the prostate cells. However, further in vitro studies in a reconstituted system using recombinant CYP27B1 revealed that 25(OH)-19-nor-D3 was hardly converted to 1alpha,25(OH)2-19-nor-D3 by the enzyme. The kinetic analysis of 1alpha hydroxylation of 25(OH)D3 and 25(OH)-19-nor-D3 demonstrated that the k(cat)/K(m) for 25(OH)-19-nor-D3 is less than 0.1% of that for 25(OH)D3. When 25(OH)-19-nor D3 was added to cultured PZ-HPV-7 cells, eight metabolites were detected, while no 1alpha,25(OH)2-19-nor-D3 was found. In addition, the time course of VDR translocation into the nucleus induced by 100 nM 25(OH)-19-nor-D3, and the subsequent transactivation of CYP24A1 gene were almost identical to those induced by 1 nM 1alpha,25(OH)2-19-nor-D3. These results strongly suggest that 25(OH)-19 nor-D3 binds directly to VDR as a ligand to transport VDR into the nucleus to induce CYP24A1 gene transactivation. Furthermore, knockdown of CYP27B1 gene did not affect the antiproliferative activity of 25(OH)-19-nor-D3, whereas VDR knockdown attenuated the effect, suggesting that the antiproliferative activity of 25(OH)-19-nor-D3 is VDR dependent but CYP27B1 independent. Finally, our recent studies using the same cell line demonstrate that 25(OH)D3 can act as a VDR agonist to induce gene transactivation. These findings suggest that vitamin D analogs without 1alpha-hydroxyl group could be developed as drugs for osteoporosis or cancer treatment. PMID- 26827960 TI - Vitamin D Analogs with Nitrogen Atom at C2 Substitution and Effect on Bone Formation. AB - The Arg274 residue of the ligand binding domain of human vitamin D receptor (hVDR) is important for 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) binding as a specific ligand through forming a hydrogen bond with the 1alpha-OH group of the active vitamin D3, 1alpha,25(OH)2D3. An additional pincer-type hydrogen bond formation with Arg274 from a 2alpha-substituent of a synthetic 1alpha,25(OH)2D3 analog would enhance the binding affinity and biological activity. A series of 2alpha-[2-(heteroaryl)ethyl]-, 2alpha-(4-cyanobutyl)-, 2alpha-(omega-cyanoalkoxy) , and 2beta-(3-cyanopropoxy)-1alpha,25(OH)2D3 were designed and synthesized based on our original hVDR super agonists of 2alpha-(3-hydroxypropyl)- and 2alpha-(3 hydroxypropoxy)-1alpha,25(OH)2D3. Their potential biological activities, i.e., hVDR binding affinity, transactivation activity in HOS cells, and therapeutic effect on enhancing the bone mineral density of OVX rats, were studied. PMID- 26827961 TI - Mechanistic Insights of Vitamin D Anticancer Effects. AB - Vitamin D is a secosteroid hormone that regulates many biological functions in addition to its classical role in maintaining calcium homeostasis and bone metabolism. Vitamin D deficiency appears to predispose individuals to increased risk of developing a number of cancers. Compelling epidemiological and experimental evidence supports a role for vitamin D in cancer prevention and treatment in many types of cancers. Preclinical studies show that 1,25D3, the active metabolite of vitamin D, and its analogs have antitumor effects in vitro and in vivo through multiple mechanisms including the induction of cell cycle arrest, apoptosis, differentiation and the suppression of inflammation, angiogenesis, invasion, and metastasis. 1,25D3 also potentiates the effect of chemotherapeutic agents and other agents in the combination treatment. In this review, the antitumor effects of 1,25D3 and the potential underlying mechanisms will be discussed. The current findings support the application of 1,25D3 in cancer prevention and treatment. PMID- 26827963 TI - Preface. PMID- 26827962 TI - Vitamin D Signaling Modulators in Cancer Therapy. AB - The antiproliferative and pro-apoptotic effects of 1alpha,25 dihydroxycholecalciferol (1,25(OH)2D3, 1,25D3, calcitriol) have been demonstrated in various tumor model systems in vitro and in vivo. However, limited antitumor effects of 1,25D3 have been observed in clinical trials. This may be attributed to a variety of factors including overexpression of the primary 1,25D3 degrading enzyme, CYP24A1, in tumors, which would lead to rapid local inactivation of 1,25D3. An alternative strategy for improving the antitumor activity of 1,25D3 involves the combination with a selective CYP24A1 inhibitor. The validity of this approach is supported by numerous preclinical investigations, which demonstrate that CYP24A1 inhibitors suppress 1,25D3 catabolism in tumor cells and increase the effects of 1,25D3 on gene expression and cell growth. Studies are now required to determine whether selective CYP24A1 inhibitors+1,25D3 can be used safely and effectively in patients. CYP24A1 inhibitors plus 1,25D3 can cause dose limiting toxicity of vitamin D (hypercalcemia) in some patients. Dexamethasone significantly reduces 1,25D3-mediated hypercalcemia and enhances the antitumor activity of 1,25D3, increases VDR-ligand binding, and increases VDR protein expression. Efforts to dissect the mechanisms responsible for CYP24A1 overexpression and combinational effect of 1,25D3/dexamethasone in tumors are underway. Understanding the cross talk between vitamin D receptor (VDR) and glucocorticoid receptor (GR) signaling axes is of crucial importance to the design of new therapies that include 1,25D3 and dexamethasone. Insights gained from these studies are expected to yield novel strategies to improve the efficacy of 1,25D3 treatment. PMID- 26827964 TI - Gene-expression signatures in ovarian cancer: Promise and challenges for patient stratification. AB - Microarray-based gene expression studies demonstrate that ovarian cancer is both a clinically diverse and molecularly heterogeneous disease compromising subtypes with distinct gene expression patterns that are each associated with statistically significant different clinical outcomes. The information provided by gene expression based assays is promising and deserves incorporation into clinical decision-making. Further studies are needed to determine which subtype signatures are most appropriate to select patients for a given therapy. This process will require the development of standardized molecular diagnostic assays that can be used for retrospective correlative studies and prospective validations of their clinical utility. Recent advances in assay development for FFPE tissues will facilitate accurate and cost-effective classification of ovarian cancer and help move the evolving molecular classification to clinic. The current review will summarize the development of gene expression based assays in ovarian cancer and will describe how the results of studies to date have expanded our appreciation of the heterogeneity of ovarian cancer. We discuss difficulties in the development and validation of molecular classifications in ovarian cancer and we provide future directions how we may be able to soon classify the disease in a manner that might have greater clinical utility. PMID- 26827965 TI - Primary site assignment in tubo-ovarian high-grade serous carcinoma: Consensus statement on unifying practice worldwide. PMID- 26827966 TI - Awards. PMID- 26827967 TI - Misleading article on palatally displaced canines. PMID- 26827968 TI - Authors' response. PMID- 26827970 TI - Is it for real? PMID- 26827971 TI - Streptococcus mutans counts in patients wearing removable retainers with silver nanoparticles vs those wearing conventional retainers: A randomized clinical trial. AB - INTRODUCTION: The rough surface of Hawley removable appliances provides an environment for plaque accumulation, leading to enamel demineralization. The aim of this study was to evaluate the effect of silver nanoparticles incorporated into acrylic baseplates of orthodontic retainers on Streptococcus mutans colony forming units. METHODS: Sixty-six orthodontic patients at the debonding stage were randomly assigned to 2 sex-matched groups with stratified block randomization: group 1 received conventional removable retainers; group 2 received removable retainers containing silver nanoparticles (about 40 nm in size and 500 ppm in concentration). After comprehensive orthodontic treatment, patients who revealed no clinical evidence of dental caries, periodontal pockets, or systemic disease were considered eligible for this study. Swab samples were taken from the maxillary palatal side from the patient in the dental chair at retainer placement (T1, 1 week after debonding the fixed orthodontic appliance) and T2, 7 weeks later. The main outcome was to compare the number of S mutans colony-forming units between the 2 groups 7 weeks after retainer delivery. The results were analyzed by using analysis of covariance. The participants and the assessors were blinded to the allocation groups. RESULTS: Twenty-nine patients in the control group and 32 in the intervention group were analyzed. At T1, the intervention group had higher S mutans colony counts relative to the control group. The analysis of covariance test showed a significant reduction of colonies in the intervention group after 7 weeks. The mean difference of colony counts between the 2 groups was 40.31 (95% confidence interval, 24.83-55.79; P < 0.001). CONCLUSIONS: Adding silver nanoparticles to the acrylic plate of retainers had a strong antimicrobial effect against S mutans under clinical conditions. REGISTRATION: This study was registered as a clinical trial at the Iranian Clinical Trial Center under the code number IRCT201309239086N2. FUNDING: This trial was supported by Hamadan Dental Research Centre, Hamadan University of Medical Sciences, Hamadan, Iran. PMID- 26827972 TI - Diagnostic accuracy and measurement sensitivity of digital models for orthodontic purposes: A systematic review. AB - INTRODUCTION: Our objective was to assess the accuracy, validity, and reliability of measurements obtained from virtual dental study models compared with those obtained from plaster models. METHODS: PubMed, PubMed Central, National Library of Medicine Medline, Embase, Cochrane Central Register of Controlled Clinical trials, Web of Knowledge, Scopus, Google Scholar, and LILACs were searched from January 2000 to November 2014. A grading system described by the Swedish Council on Technology Assessment in Health Care and the Cochrane tool for risk of bias assessment were used to rate the methodologic quality of the articles. RESULTS: Thirty-five relevant articles were selected. The methodologic quality was high. No significant differences were observed for most of the studies in all the measured parameters, with the exception of the American Board of Orthodontics Objective Grading System. CONCLUSIONS: Digital models are as reliable as traditional plaster models, with high accuracy, reliability, and reproducibility. Landmark identification, rather than the measuring device or the software, appears to be the greatest limitation. Furthermore, with their advantages in terms of cost, time, and space required, digital models could be considered the new gold standard in current practice. PMID- 26827973 TI - Impact of orthosurgical treatment phases on oral health-related quality of life. AB - INTRODUCTION: In this cross-sectional study, we investigated the impact of the orthosurgical treatment phases on the oral health-related and condition-specific quality of life (QoL) of patients with dentofacial deformities. METHODS: Two hundred fifty-four orthognathic patients were allocated into 4 groups according to treatment phase: initial (not yet treated), presurgical orthodontics, postsurgical orthodontics, and retention. Data were collected using the Oral Health Impact Profile to evaluate the oral health-related QoL, the Orthognathic QoL Questionnaire to analyze the condition-specific QoL, and the Index of Orthodontic Treatment Need to assess malocclusion severity and esthetic impairment. Specific malocclusion characteristics were also documented. RESULTS: A negative binomial regression analysis showed that the initial group had a more negative oral health-related QoL than did the postsurgical, presurgical, and retention groups (relative risks, 1, 0.79, 0.74 and 0.25, respectively). The initial group had a more negative condition-specific QoL than did the presurgical, postsurgical, and retention groups (relative risks, 1, 0.77, 0.38 and 0.15, respectively) regardless of age, income, or education; women reported greater negative impacts than men. Certain occlusal traits were related to higher Orthognathic QoL Questionnaire scores (P <0.01). CONCLUSIONS: Patients who completed their orthosurgical treatment had a significantly better oral health related QoL and a more positive esthetic self-perception than did those undergoing treatment and those who were untreated. Crowding, crossbite, open bite, concave profile, edge-to-edge overjet, or Class III malocclusion negatively affected oral health-related QoL. PMID- 26827975 TI - Evaluation of marginal alveolar bone in the anterior mandible with pretreatment and posttreatment computed tomography in nonextraction patients. AB - INTRODUCTION: Our objectives were to evaluate marginal alveolar bone height in the anterior mandible after orthodontic treatment and to assess any correlations between morphologic and treatment changes. METHODS: We used 57 pretreatment and posttreatment cone-beam computed tomography images (17 male and 40 female subjects; 22 Class I, 35 Class II; average age, 18.7 +/- 10.8 years; average treatment time, 22.7 +/- 7.3 months) to measure cortical bone thickness, ridge thickness, distance from the apex to the labial cortical bone, and the distance from the cementoenamel junction to the marginal bone crest. Changes in the cementoenamel junction to the marginal bone crest distance were correlated with pretreatment measurements and treatment changes. RESULTS: Although there were great variations, the average facial and lingual vertical bone losses were 1.16 +/- 2.26 and 1.33 +/- 2.50 mm, respectively. The incisor-mandibular plane angle changes were also highly variable, averaging 2.4 degrees . CONCLUSIONS: Orthodontic treatment causes changes in alveolar bone height and cortical bone thickness around the mandibular incisors. Although pretreatment cortical bone thickness, ridge width thickness, and specific tooth movements all play roles in what happens to the bone during treatment, incisor inclination was not correlated with alveolar bone height changes. PMID- 26827974 TI - Facial morphology in children and adolescents with juvenile idiopathic arthritis and moderate to severe temporomandibular joint involvement. AB - INTRODUCTION: The aims of this study were to (1) assess lateral facial morphology in children and adolescents with juvenile idiopathic arthritis and moderate to severe temporomandibular joint (TMJ) involvement, (2) compare the lateral facial morphology of these subjects with and without TMJ involvement using cephalograms and 3-dimensional (3D) facial photographs, and (3) compare and correlate the results of the 3D photographic and cephalometric analyses. METHODS: Sixty patients with juvenile idiopathic arthritis were included and grouped as follows: group 1, juvenile idiopathic arthritis patients without TMJ involvement; group 2, juvenile idiopathic arthritis patients with moderate to severe unilateral TMJ involvement; and group 3, juvenile idiopathic arthritis patients with moderate to severe bilateral TMJ involvement. Lateral cephalograms were used to assess and compare lateral facial morphologies between the groups. Lateral projections of oriented 3D photographs were superimposed on the lateral cephalograms. The results of the lateral 3D photographic analysis were correlated with those of lateral cephalometric analysis. RESULTS: Group 3 showed the most severe growth disturbances, including more retrognathic mandible and retruded chin, steep occlusal and mandibular planes, and more hyperdivergent type (P <0.01). Group 2 showed similar growth disturbances, but to a lesser extent than did group 3. Photographic variables were significantly correlated with the soft tissue and skeletal variables of cephalograms (0.5 < r < 0.9; P <0.001). CONCLUSIONS: Subjects with juvenile idiopathic arthritis and unilateral or bilateral moderate to severe TMJ involvement had significant growth disturbances. Early intervention is recommended for these patients to prevent unfavorable facial development. Furthermore, with proper orientation, 3D photographs can be used as an alternative to conventional lateral cephalograms and 2-dimensional photographs. PMID- 26827976 TI - Unexpected complications associated with mandibular fixed retainers: A retrospective study. AB - INTRODUCTION: The purposes of this retrospective study were to describe the types of unexpected complications associated with mandibular fixed retainers and to assess their prevalences and possible etiologic causes. METHODS: A total of 3500 consecutive patients (1423 male, 2077 female) treated with fixed appliances and a mandibular fixed retainer as a part of the retention protocol were screened during the retention period (2008-2013) for unexpected complications. Thirty eight subjects (12 male, 26 female; mean age, 20.7 +/- 8.9 years) with unexpected complications were identified and assigned to the unexpected complications group and compared with a randomly selected control group of 105 subjects (43 men, 62 women; mean age, 29.5 +/- 9.7 years) without unexpected complications. Relationships between unexpected complications and cephalometric and clinical variables were evaluated. RESULTS: An opposite inclination of the contralateral canines (twist effect) was found in 21 subjects. In 89.5%, the left canines were tipped buccally. A torque difference of 2 adjacent incisors (X effect) was identified in 12 patients. In 5 subjects, nonspecific complications were noted. Subjects in the unexpected complications group were significantly younger at debonding (P = 0.03) and had higher mandibular plane angles (P <0.0001) and increased pretreatment ventral positions of the mandibular incisors (P = 0.029). No differences were found between the groups with regard to treatment duration, wire type, failure rate, treatment changes in incisor proclination, or intercanine distance. CONCLUSIONS: Unexpected complications of mandibular fixed retainers are relatively rare. Facial divergence was identified as a possible predictor. However, the etiology is most likely multifactorial. Strong asymmetry among the patients with the twist effect suggests that the mechanical properties of retention wires may play a role and should be examined in the future. PMID- 26827977 TI - In-vitro bond strengths and clinical failure rates of metal brackets bonded with different light-emitting diode units and curing times. AB - INTRODUCTION: The purpose of this study was to compare the clinical failure rates and the in-vitro bond strengths of metal brackets bonded with different light emitting diode (LED) devices and curing times. METHODS: Forty patients were included in the clinical part of this study. A split-mouth design was used, with the adhesive in group 1 cured for 10 seconds with an LED unit (Elipar S10; 3M Unitek, Monrovia, Calif), and the adhesive in group 2 cured for 3 seconds with another LED unit (VALO Ortho; Ultradent Products, South Jordan, Utah). Bond failures during 12 months of orthodontic treatment were recorded. In-vitro performance of the brackets was also compared by bonding brackets to extracted premolars and using the same light units and curing times (n = 20 for each group). The adhesive remnant index was used to determine the bond failure interface. RESULTS: Clinical bond failure rates were 2.90% for the Elipar and 3.16% for the VALO curing units. The difference in bracket failure rates between the 2 LED devices was not statistically significant. No statistically significant difference was found between the in-vitro bond strengths of the groups. CONCLUSIONS: Our findings regarding long-term clinical survival rates and in vitro bond strengths indicate that bracket bonding can be safely accomplished in 10 seconds of light-curing with an Elipar LED and 3 seconds of light-curing with a VALO LED. PMID- 26827978 TI - Bone density effects on the success rate of orthodontic microimplants evaluated with cone-beam computed tomography. AB - INTRODUCTION: The purpose of this study was to evaluate the effect of bone densities on the success rate of orthodontic microimplants with cone-beam computed tomography images. METHODS: We examined 127 orthodontic microimplants implanted into the maxillary buccal alveolar bone of 71 patients (53 female, 18 male; mean age, 19.2 years) with malocclusion. The cortical, cancellous, and total bone densities were measured with Simplant Pro 2011 software (version 13; Materialise, Leuven, Belgium), and the correlations between these measurements and the orthodontic microimplant success rates were evaluated with cone-beam computed tomography. RESULTS: The overall success rate was 85.0% (108 of 127). Sex, age, and side of placement were not significant factors for success in the results (P >0.05). The density of the cortical bone increased apically (3, 5, and 7 mm) from the alveolar crest, but in the cancellous bone it decreased. Whereas the orthodontic microimplant success rates significantly increased as cancellous bone density and total bone density increased (P <0.01), cortical bone density did not have a significant effect on the success rate (P >0.05). CONCLUSIONS: The success rate of orthodontic microimplants significantly increased with higher cancellous and total bone densities, whereas cortical bone density did not have a significant effect. PMID- 26827979 TI - Evaluation of facial hard and soft tissue asymmetry using cone-beam computed tomography. AB - INTRODUCTION: The purposes of this study were to (1) evaluate facial asymmetry 3 dimensionally using cone-beam computed tomography (CBCT) and (2) compare the right and left facial hard and soft tissues volumetrically and their interferences on each other. METHODS: The CBCT data of 49 asymmetric (soft tissue menton deviation, >=4 mm; distance from the facial midline) (mean age, 19.9 +/- 5.6 years) and 39 symmetric patients (soft tissue menton deviation, <4 mm) (mean age, 17.8 +/- 5.5 years) were exported to the MIMICS software program (version 13.0; Materialise, Leuven, Belgium). Linear, surface distance, angular, volumetric, and surface area measurements were performed 3 dimensionally to assess and compare intragroup and intergroup differences. RESULTS: In the asymmetry group, linear measurements such as ramus height, mandibular effective and corpus length, and absolute mandibular volumetric measurements were significantly decreased (P <0.001), whereas facial mandibular, and soft and hard tissue volumetric measurements made on 3-dimensional images, and linear measurements on 2-dimensional images were increased (P <0.001) on the deviation side. CONCLUSIONS: Facial hard and soft tissue asymmetries can be precisely quantified using CBCT. However, especially in the gonial region where the surface topography shows alterations caused by asymmetry, many anatomic landmarks should be chosen for the assessment of asymmetry. At the gonial level, the compensation of the soft tissues for the hard tissues was found on 2-dimensional images; nevertheless, 3-dimensional right and left volumetric soft tissue evaluations provide evidence for asymmetry. PMID- 26827980 TI - Caries prevention during orthodontic treatment: In-vivo assessment of high fluoride varnish to prevent white spot lesions. AB - INTRODUCTION: Our objective was to evaluate the efficacy of a fluoridated varnish in preventing white spot lesions in patients with fixed appliances. A laser induced fluorescence device was used to determine any correlations between the degree of demineralization and the length of the observation period, the arch sector, the frequency of varnish application, and the specific tooth site. METHODS: A split-mouth study design was used for 24 orthodontic patients, allocated randomly to 2 subgroups with differing frequencies of Duraphat varnish (Colgate-Palmolive, New York, NY) application. Repeated measures of the degree of demineralization were taken on the vestibular surfaces of 12 teeth (6 varnished and 6 unvarnished controls). Measurements were taken at 4 sites using a DIAGNOdent Pen 2190 laser (KaVo, Biberach an der Riss, Germany) and then subjected to statistical analysis. RESULTS: Generalized linear model and coefficient model analysis showed differences in the degrees of demineralization between treated and untreated teeth, but this was not statistically significant in terms of time point, frequency of application, or specific tooth site. However, when we analyzed the position of the teeth, the varnished anterior teeth showed a statistically significant reduction in demineralization compared with their unvarnished counterparts. CONCLUSIONS: Periodic application of fluoride varnish can offer some protection against white spots, but not to a statistically significant degree if the patients have excellent oral hygiene. PMID- 26827981 TI - Progressive changes in patients with skeletal Class III malocclusion treated by 2 jaw surgery with minimal and conventional presurgical orthodontics: A comparative study. AB - INTRODUCTION: In this study, we aimed to compare treatment efficacy and postsurgical stability between minimal presurgical orthodontics and conventional presurgical orthodontics for patients with skeletal Class III malocclusion. METHODS: Forty patients received minimal presurgical orthodontics (n = 20) or conventional presurgical orthodontics (n = 20). Lateral cephalograms were obtained before treatment, before orthognathic surgery, and at 1 week, 3 months, 6 months, and 12 months after surgery. RESULTS: Changes of overjet and mandibular incisal angle before surgery were greater in the conventional presurgical orthodontics group than in the minimal presurgical orthodontics group. Postsurgical horizontal changes in Points A and B, overjet, and mandibular incisal angle showed significant differences among the time points. Most of the horizontal and vertical relapses in the maxilla and the mandible occurred within the first 6 months in both groups. CONCLUSIONS: Minimal presurgical orthodontics and conventional presurgical orthodontics showed similar extents and directions of skeletal changes in patients with Class III malocclusion. However, orthodontists and surgeons should preoperatively consider the postsurgical counterclockwise rotation of the mandible when using minimal presurgical orthodontics. Close and frequent observations are recommended in the early postsurgical stages. PMID- 26827982 TI - University clinic and private practice treatment outcomes in Class I extraction and nonextraction patients: A comparative study with the American Board of Orthodontics Objective Grading System. AB - INTRODUCTION: The aim of this study was to compare treatment outcomes in university vs private practice settings with Class I patients using the American Board of Orthodontics Objective Grading System. METHODS: A parent sample of 580 Class I patients treated with and without extractions of 4 first premolars was subjected to discriminant analysis to identify a borderline spectrum of 66 patients regarding the extraction modality. Of these patients, 34 were treated in private orthodontic practices, and 32 were treated in a university graduate orthodontic clinic. The treatment outcomes were evaluated using the 8 variables of the American Board of Orthodontics Objective Grading System. RESULTS: The total scores ranged from 10 to 47 (mean, 25.44; SD, 9.8) for the university group and from 14 to 45 (mean, 25.94; SD, 7.7) for the private practice group. The university group achieved better scores for the variables of buccolingual inclination (mean difference, 2.28; 95% confidence interval [CI], 0.59, 3.98; P = 0.01) and marginal ridges (mean difference, 1.32; 95% CI, 0.28, 2.36; P = 0.01), and the private practice group achieved a better score for the variable of root angulation (mean difference, -0.65; 95% CI, -1.26, -0.03; P = 0.04). However, no statistically intergroup differences were found between the total American Board of Orthodontics Objective Grading System scores (mean difference, -0.5; 95% CI, 3.82, 4.82; P = 0.82). CONCLUSIONS: Patients can receive similar quality of orthodontic treatment in a private practice and a university clinic. The orthodontists in the private practices were more successful in angulating the roots properly, whereas the orthodontic residents accomplished better torque control of the posterior segments and better marginal ridges. PMID- 26827983 TI - Preoperative and postoperative examination of occlusal and maxillofacial changes after osteochondroma extirpation. AB - A patient came with left-side temporomandibular arthralgia, limited mandibular opening, frontal facial asymmetry, and a significant anterolateral open bite. Severe alterations in the occlusal and maxillofacial anatomy resulted from an osteochondroma associated with the mandibular condyle. We describe the changes associated with extirpation of the mandibular condylar osteochondroma and subsequent orthodontic treatment. These clinical changes resulted in improved facial symmetry and a satisfactory functional occlusion. PMID- 26827984 TI - Open-bite treatment with vertical control and tongue reeducation. AB - An open-bite malocclusion with a tongue-thrust habit is a challenging type of malocclusion to correct. A 12-year-old girl came for orthodontic treatment with a severe anterior open bite, extruded posterior segments, a tongue-thrust habit, and lip incompetency. Her parents refused surgical treatment, so a nonextraction treatment plan was developed that used palatal temporary skeletal anchorage devices for vertical control and mandibular tongue spurs to reeducate the tongue. Interproximal reduction was also used to address the moderate to severe mandibular crowding. An abnormal Class I occlusion was achieved with proper overbite and overjet, along with a pleasing smile and gingival display. PMID- 26827985 TI - Inadvertent tooth movement with fixed lingual retainers. AB - Fixed retainers are effective in maintaining the alignment of the anterior teeth more than 90% of the time, but they can produce inadvertent tooth movement that in the most severe instances requires orthodontic retreatment managed with a periodontist. This is different from relapse into crowding when a fixed retainer is lost. These problems arise when the retainer breaks but remains bonded to some or all teeth, or when an intact retainer is distorted by function or was not passive when bonded. In both instances, torque of the affected teeth is the predominant outcome. A fixed retainer made with dead soft wire is the least likely to create torque problems but is the most likely to break. Highly flexible twist wires bonded to all the teeth appear to be the most likely to produce inadvertent tooth movement, but this also can occur with stiffer wires bonded only to the canines. Orthodontists, general dentists, and patients should be aware of possible problems with fixed retainers, especially those with all teeth bonded, because the patient might not notice partial debonding. Regular observations of patients wearing fixed retainers by orthodontists in the short term and family dentists in the long term are needed. PMID- 26827986 TI - Dimensional accuracy of digital dental models from cone-beam computed tomography scans of alginate impressions according to time elapsed after the impressions. AB - INTRODUCTION: Our objective was to investigate the dimensional accuracy of digital dental models obtained from the cone-beam computed tomography (CBCT) scans of alginate impressions according to the time elapsed after the impressions were taken. METHODS: Alginate impressions were obtained of 20 adults using 2 alginate materials: Alginoplast (Heraeus Kulzer, Hanau, Germany) and Cavex (Cavex Holland, Haarlem, The Netherlands). These impressions were stored in wet conditions and scanned by CBCT immediately after impression-taking and after storage times of 12, 24, 36, 48, 60, and 72 hours. After reconstruction of the 3 dimensional digital dental models, the models were measured, and the data were analyzed to determine the dimensional changes according to the time elapsed. The changes within the measurement error were regarded as clinically acceptable in this study. RESULTS: The measurement errors ranged from 0.27 to 0.29 mm in the digital dental models obtained from CBCT scans of the alginate impressions. All measurements showed decreasing accuracy with greater elapsed time after the impressions were taken. Changes above the measurement error occurred at 24 and 36 hours for Cavex and Alginoplast, respectively. CONCLUSIONS: Digital dental models can be obtained from CBCT scans of alginate impressions without sending them to a remote laboratory. However, the impressions need to be scanned within 24 hours; otherwise, dimensional changes lead to errors that exceed the error of measurement. PMID- 26827987 TI - Litigation and Legislation. It's irrelevant. PMID- 26827988 TI - Microbial production of bi-functional molecules by diversification of the fatty acid pathway. AB - Fatty acids that are chemically functionalized at their omega-ends are rare in nature yet offer unique chemical and physical properties with wide ranging industrial applications as feedstocks for bio-based polymers, lubricants and surfactants. Two enzymatic determinants control this omega-group functionality, the availability of an appropriate acyl-CoA substrate for initiating fatty acid biosynthesis, and a fatty acid synthase (FAS) variant that can accommodate that substrate in the initial condensation reaction of the process. In Type II FAS, 3 ketoacyl-ACP synthase III (KASIII) catalyses this initial condensation reaction. We characterized KASIIIs from diverse bacterial sources, and identified variants with novel substrate specificities towards atypical acyl-CoA substrates, including 3-hydroxybutyryl-CoA. Using Alicyclobacillus acidocaldarius KASIII, we demonstrate the in vivo diversion of FAS to produce novel omega-1 hydroxy branched fatty acids from glucose in two bioengineered microbial hosts. This study unveils the biocatalytic potential of KASIII for synthesizing diverse omega functionalized fatty acids. PMID- 26827989 TI - Obesity-induced p53 activation in insulin-dependent and independent tissues is inhibited by beta-adrenergic agonist in diet-induced obese rats. AB - AIMS: The purpose of this study was to assay the role of beta-adrenergic receptor signaling in the regulation of obesity-induced p53 in high fat feeding obese rats. MAIN METHODS: The role of beta-adrenergic receptor/cyclic AMP in the regulation of p53 and its downstream mediators was evaluated by western blot and real-time quantitative RT-PCR among diet induced rats. KEY FINDINGS: Beta adrenergic receptor agonist, isoproterenol, and an adenylate cyclase activator, forskolin, at a single dose significantly reduced insulin resistance consistent with a decrease in total and phospho-p53 levels in insulin and non-insulin metabolic target tissues. The decrease of p53 signaling was consistent with the elevation of AKT and subsequent activation. Obese rats exposed to fasting also exhibited improvement in insulin action despite a slight effect on p53 level. SIGNIFICANCE: Results of the present study obviously showed that beta-adrenergic receptor agonist/cAMP prevented obesity-induced p53 activation. Although this effect in metabolic insulin target tissues tempted us to consider them as insulin sensitizers in obesity-related diabetes, p53 inhibition in non-insulin target tissues warned about the impairment of anti-cancer mechanisms in obese subjects. PMID- 26827990 TI - Amygdalin delays cell cycle progression and blocks growth of prostate cancer cells in vitro. AB - AIMS: Despite impressive survival benefits from new agents to treat metastasized prostate cancer (PCa), progressive drug resistance hinders long-term response and restricts the efficacy of subsequent therapy. Due to reported antitumor activity of amygdalin and growing popularity for complementary and alternative medicine the potential of this natural, widely used substance to exert antineoplastic effects on prostate cancer cells has been assessed. MAIN METHODS: LNCaP (castration-sensitive), DU-145 and PC3 cells (castration-resistant) were exposed to different concentrations of amygdalin for 24h or 2weeks. Cell growth was measured by the MTT test, clonal formation by the clonogenic assay. Flow cytometry served to investigate apoptosis and cell cycle phases. Cell cycle regulating proteins and the mTOR-akt signaling axis were analyzed by western blotting. KEY FINDINGS: Amygdalin dose-dependently diminished tumor cell growth with maximum effects at 10mg/ml. Apoptosis of PC3 and LNCaP but not of DU-145 cells was reduced, whereas colony formation was suppressed in all cell lines. A decrease in the number of G2/M- and S-phase cells along with an elevated number of G0/G1-phase cells was recorded. The cell cycle proteins cdk 1, cdk 2 and cdk 4 as well as cyclin A, cyclin B and cyclin D3 were modulated by amygdalin after both 24h and 2weeks. Distinct effects on p19 and p27 expression and on Akt, Rictor and Raptor activation became evident only after 2weeks. SIGNIFICANCE: Amygdalin exhibits significant antitumor activity in both castration-sensitive and castration-resistant PCa cell lines and merits further evaluation for therapeutic purposes. PMID- 26827991 TI - MicroRNA-103/107 is involved in hypoxia-induced proliferation of pulmonary arterial smooth muscle cells by targeting HIF-1beta. AB - AIMS: Activation of hypoxia inducible factor-1 (HIF) is a hallmark in hypoxia induced pulmonary hypertension (HPH). microRNAs play a significant role in regulating proliferation of pulmonary arterial smooth muscle cells (PASMCs) in pulmonary hypertension. Previous studies have shown that HIF-1beta is a target of miR-103/107. In this present study, we aimed to investigate whether miR-103/107 regulate vascular remodeling in HPH via HIF-1beta. MAIN METHODS: The HPH model was built by hypoxia exposure in rats. Real-time PCR and Western blotting were used to determine the expression of miR-103/107 and HIF-1beta. Proliferation of PASMCs was examined by 5-bromo-2'-deoxyuridine (BrdU) incorporation method. The functions of miR-103/107 on PASMCs proliferation, HIF-1alpha and HIF-1beta expression were assessed by transfecting miR-103/107 mimics and inhibitors. KEY FINDINGS: Significant down-regulation of miR-103/107 was observed in remodeled intrapulmonary vascular in HPH rats and hypoxia-exposured PASMCs, whereas HIF 1alpha and HIF-1beta expression were up-regulated. Hypoxia exposure induced significant proliferation of PASMCs, overexpression of miR-103/107 inhibited but miR-103/107 inhibitors exacerbated PASMCs proliferation. Gain-of-function and loss-of-function experiments showed that miR-103/107 expression was inversely correlated with HIF-1beta level. No significant changes of HIF-1alpha expression were observed under miR-103/107 mimic treatment. SIGNIFICANCE: Loss of suppression on HIF-1beta by miR-103/107 may contribute to excess proliferation of PASMCs and vascular remodeling in hypoxic pulmonary hypertension. PMID- 26827992 TI - A high-throughput method for liquid chromatography-tandem mass spectrometry determination of plasma alkylresorcinols, biomarkers of whole grain wheat and rye intake. AB - Plasma alkylresorcinols are increasingly analyzed in cohort studies to improve estimates of whole grain intake and their relationship with disease incidence. Current methods require large volumes of solvent (>10 ml/sample) and have relatively low daily sample throughput. We tested five different supported extraction methods for extracting alkylresorcinols from plasma and improved a normal-phase liquid chromatography coupled to a tandem mass spectrometer method to reduce sample analysis time. The method was validated and compared with gas chromatography-mass spectrometry analysis. Sample preparation with HybridSPE supported extraction was most effective for alkylresorcinol extraction, with recoveries of 77-82% from 100 MUl of plasma. The use of 96-well plates allowed extraction of 160 samples per day. Using a 5-cm NH2 column and heptane reduced run times to 3 min. The new method had a limit of detection and limit of quantification equivalent to 1.1-1.8 nmol/L and 3.5-6.1 nmol/L plasma, respectively, for the different alkylresorcinol homologues. Accuracy was 93-105%, and intra- and inter-batch precision values were 4-18% across different plasma concentrations. This method makes it possible to quantify plasma alkylresorcinols in 100 MUl of plasma at a rate of at least 160 samples per day without the need for large volumes of organic solvents. PMID- 26827994 TI - HRI Rome 2015 - Homeopathy research gathers momentum. PMID- 26827995 TI - Cutting Edge Research in Homeopathy: HRI's second international research conference in Rome. AB - Rome, 3rd-5th June 2015, was the setting for the Homeopathy Research Institute's (HRI) second conference with the theme 'Cutting Edge Research in Homeopathy'. Attended by over 250 delegates from 39 countries, this event provided an intense two and a half day programme of presentations and a forum for the sharing of ideas and the creation of international scientific collaborations. With 35 oral presentations from leaders in the field, the scientific calibre of the programme was high and the content diverse. This report summarises the key themes underpinning the cutting edge data presented by the speakers, including six key note presentations, covering advancements in both basic and clinical research. Given the clear commitment of the global homeopathic community to high quality research, the resounding success of both Barcelona 2013 and Rome 2015 HRI conferences, and the dedicated support of colleagues, the HRI moves confidently forward towards the next biennial conference. PMID- 26827996 TI - Homeopathic Rhus toxicodendron has dual effects on the inflammatory response in the mouse preosteoblastic cell line MC3T3-e1. AB - BACKGROUND: Homeopathic remedy Rhus toxicodendron (Rhus tox) is used for several symptoms including skin irritations, rheumatic pains, mucous membrane afflictions, and typhoid type fever. Previously, we reported that Rhus tox treatment increased the cyclooxygenase-2 (COX-2) mRNA expression in primary cultured mouse chondrocytes. METHODS: A preosteoblastic mouse cell line, MC3T3 e1, was treated with different homeopathic dilutions of Rhus tox and the COX-2 mRNA and protein expression was examined using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblotting. Additionally, nitric oxide (NO) generation was examined in LPS-induced MC3T3-e1 cells using a Griess reaction assay. RESULTS: Stimulation with different concentrations of Rhus tox increased the expression of Cox2 mRNA, with 30X Rhus tox showing the most prominent increase in mRNA expression. In addition, treatment with 30X Rhus tox significantly increased prostaglandin E2 (PGE2) release compared with other homeopathic dilutions. However, the COX-2 protein expression level differed slightly from its mRNA expression, because the 30C Rhus tox treatment increased COX-2 protein to a greater extent compared with other dilutions. NO generation was dramatically decreased in MC3T3-e1 cells after Rhus tox treatment co stimulated with lipopolysaccharide. CONCLUSION: Homeopathic dilution of Rhus tox has a dual activity that increases COX-2 expression and decreases NO generation, thus modulating inflammation. Further study is needed to examine the cellular signaling mechanisms that are associated with inflammatory regulation by Rhus tox treatment in greater detail. PMID- 26827998 TI - Solvatochromic dyes detect the presence of homeopathic potencies. AB - A systematic approach to the design of simple, chemical systems for investigating the nature of homeopathic medicines has led to the development of an experimental protocol in which solvatochromic dyes are used as molecular probes of serially diluted and agitated solutions. Electronic spectroscopy has been used to follow changes in the absorbance of this class of dyes across the visible spectrum in the presence of homeopathic potencies. Evidence is presented using six different solvatochromic dyes in three different solvent systems. In all cases homeopathic potencies produce consistent and reproducible changes in the spectra of the dyes. Results suggest that potencies influence the supramolecular chemistry of solvatochromic dyes, enhancing either dye aggregation or disaggregation, depending upon dye structure. Comparable dyes lacking the intramolecular charge transfer feature of solvatochromic dyes are unaffected by homeopathic potencies, suggesting potencies require the oscillating dipole of solvatochromic dyes for effective interaction. The implications of the results presented, both for an eventual understanding of the nature of homeopathic medicines and their mode of action, together with future directions for research in this area, are discussed. PMID- 26827997 TI - Standardization of homeopathic mother tincture of Toxicodendron pubescens and correlation of its flavonoid markers with the biological activity. AB - BACKGROUND: Standardization and quality control of homeopathic drugs is very challenging. As mother tinctures are derived from complex natural resources, there is a need of systematic evaluation of chemical markers which correlate with the proposed biological activities of mother tinctures. METHODS: In present study, High-Performance Thin-Layer Chromatography (HPTLC) standardization method of homeopathic mother tinctures of Toxicodendron pubescens using quercitrin and rutin as chemical markers is validated and correlations of content of these markers with its anti-inflammatory effects are established. For HPTLC analysis, precoated silica gel plates were used as stationary phase. Two flavonoids, namely quercitrin and rutin were used as markers. Separation was achieved using methylene chloride:methanol:water:glacial acetic acid (15:1.5:1:8 v/v/v) as mobile phase. The developed plates were scanned at 365 nm. RESULTS: It was observed that quercitrin (Rf value 0.63) and Rutin (Rf value 0.41) are well resolved. The minimum detectable concentrations for quercitrin and rutin were 5 ng/spot. The linearity range was between 100 and 2000 ng/spot for both the markers. Subsequently, anti-inflammatory activity of these formulations was determined against carrageenan-induced paw edema in rats, pain threshold determined by electronic Von-Frey apparatus and paw withdrawal latency (PWL) on hot-plate. All the tested formulations of Rhus Tox showed anti-inflammatory and analgesic activity against carrageenan induced paw edema in rats. Quantitative correlation between the content of markers and anti-inflammatory activity of mother tinctures was established. RESULTS: Anti-inflammatory effect as well as effect on paw withdrawal and pain threshold, at third hour after carrageenan injection, correlated with quercitrin and rutin content in the respective formulations. CONCLUSIONS: This study validates a quantitative HPTLC method for standardization of homeopathic mother tincture of Rhus Tox and establishes quercitrin and rutin as markers corresponding its biological activity. Contents of quercitrin and rutin in T. pubescens mother tincture correlates with its anti inflammatory and analgesic actions and the validated HPTLC method can be used in standardization of homeopathic mother tincture of T. pubescens. PMID- 26827999 TI - A randomized controlled trial comparing Pentazocine and Chamomilla recutita for labor pain relief. AB - BACKGROUND: Traditional birth attendants in Pakistan sometimes use a homeopathic remedy, Chamomilla for labor pain relief. Our study compares this homeopathic remedy for pain relief in labor with a commonly used parenteral analgesic in a hospital setting. No systematic study has been conducted previously to study the effect of chamomile, which may be affordable and available in community settings. METHODS: A double blind randomized controlled trial was carried out at Islamic International Medical College Trust. Ninety-nine normal pregnant women were randomly assigned into three groups. Each group received one of the three trial drugs; Chamomile, Pentazocine or placebo. The efficacy of labor analgesia was assessed by using Visual Analogue Scale (VAS) for pain intensity. Indicators of maternal and child health were recorded as were adverse effects of the drugs. RESULTS: Mean pain scores in the three groups were calculated and compared. The difference in mean VAS scores in Pentazocine and Chamomilla recutita group as compared with placebo was not statistically significant. No significant adverse effects were noticed in any group except slight headache and dizziness in three parturients in Pentazocine group. CONCLUSION: Neither Pentazocine, or Chamomilla recutita offer substantial analgesia during labor. PMID- 26828000 TI - Homeopathic medicines for prevention of influenza and acute respiratory tract infections in children: blind, randomized, placebo-controlled clinical trial. AB - BACKGROUND: Influenza and its complications are common at all ages, especially in children. Vaccines and anti-influenza drugs aim to prevent it. Preventative approaches with favorable risk profiles should be considered for flu, particularly since the evidence of the efficacy of anti-viral drugs is debated. METHODS: This pragmatic clinical trial was conducted in the Brazilian Public Health System in Petropolis (BPHSP) with children aged from 1 to 5 years old. The medications used were mainly selected based on in vitro experiments (InfluBio), and in successful qualitative clinical experiences (Homeopathic Complex). Following informed parental consent, subjects were randomly distributed, in a blind manner, to three experimental groups: Homeopathic Complex, Placebo, and InfluBio. BPHSP health agents collected flu and acute respiratory infection symptomatic episodes monthly following the established protocol. The number of these episodes was registered in one year (2009-2010). RESULTS: Out of the 600 children recruited, 445 (74.17%) completed the study (149: Homeopathic complex; 151: Placebo; 145: InfluBio). The number of flu and acute respiratory infection symptomatic episodes detected in this clinical trial was low; however, it was different between homeopathic groups and placebo (p < 0.001). In the first year post-intervention, 46/151 (30.5%) of children in the placebo group developed 3 or more flu and acute respiratory infection episodes, while there was no episode in the group of 149 children who used Homeopathic Complex, and only 1 episode in the group of 145 (1%) children who received InfluBio. CONCLUSION: These results suggested that the use of homeopathic medicines minimized the number of flu and acute respiratory infection symptomatic episodes in children, signalizing that the homeopathic prophylactic potential should be investigated in further studies. PMID- 26828001 TI - Prevalence and likelihood ratio of symptoms in patients with good therapeutic response to Lycopodium clavatum. A retrospective study. AB - BACKGROUND: Assessment of the likelihood ratio (LR) of symptoms has been proposed as a rational means for detecting indicators to homeopathic medicines. AIMS: To investigate the prevalence and LR of symptoms commonly attributed to the homeopathic medicine Lycopodium clavatum (Lyc). Secondarily, to answer the question if experienced homeopaths could intuitively infer which the main symptoms of this medicine are. METHODS: The presence of 35 selected symptoms, prescribed medicines and therapeutic response were assessed retrospectively. The symptoms' prevalence in the Lyc responding population and the LR of the symptoms compared to their prevalence in the remainder of the population were calculated. RESULTS: Two hundred and two Lyc and 550 non Lyc cases (total 752) were included for analysis. Twenty-two symptoms were confirmed as pertaining to Lyc's semiology (prevalence %; LR): contemptuous (3.3; 6.7), urinary stones history (2.7; 5.4), egotism (5.6; 3.6), dictatorial (33.3; 3.4), haughty (8.7; 3.3), sleeps on abdomen (3.3; 3.3), intolerance to clothing in abdomen (12.0; 3.1), reproaches (4.0; 3.0), helplessness (24.0; 2.7), fear of failure (10.7; 2.6), irritability on waking in the morning (16.7; 2.5), constipation alternating with diarrhea (8.7; 2.5), intolerant to contradiction (59.3; 2.3), want of self confidence (30.0; 2.4), abdominal distension after eating (23.3; 2.1); ailments from anticipation (32.0; 1.9), irritability before menses (23.3; 1.8), conscientious (26.0; 1.6), desire of sweets (52.0; 1.6), desire of chocolate (16.7; 1.6), lack of vital heat (41.3; 1.3), and flatterer (1.3; infinity). Surveyed homeopaths' intuitive inferences correlated well with symptoms' prevalence but not with their LR. CONCLUSIONS: Lycopodium's main symptoms are well known by homeopaths, but their knowledge correlates well with the symptoms' prevalence and not with their LR. Retrospective assessment of prevalence and LR of symptoms in good responders might be a means for better selection of symptoms for prospective studies. PMID- 26828002 TI - Open-label observational study of the homeopathic medicine Passiflora Compose for anxiety and sleep disorders. AB - BACKGROUND: Anxiety and sleep disorders (SDS) are frequently treated with psychotropic drugs. Health authorities in France have been advised to improve access to alternative treatments such as homeopathic medicines. Our aim was to describe the socio-demographic characteristics and clinical progression of patients prescribed homeopathic medicine Passiflora Compose (PC) for anxiety and/or SDS. MATERIAL AND METHODS: This was an open-label, observational study. Randomly selected general practitioners (GPs) known to prescribe homeopathic medicines recruited consecutive patients (>=18-years) prescribed PC. The following data were recorded at inclusion by the GP: socio-demographic data and anxiety severity (Hamilton anxiety rating scale or HAM-A); and by the patients: level of anxiety (STAI Spielberger self-assessment questionnaire) and SDS (Jenkins sleep scale or JSS). Anxiety and SDS were reassessed after 4 weeks of treatment using the same scales. RESULTS: A total of 639 patients (mean age: 46.3 +/- 17.5 years; 78.6% female) were recruited by 98 GPs. Anxiety was present in 85.4% (HAM-A) and 93.3% (Spielberger State) at inclusion (mean scores: 17.8 +/- 8.91 and 54.59 +/- 11.69, respectively) and SDS was present in 74.0% (mean score: 15.24 +/- 5.28). A total of 401 (62.7%) patients received PC alone and 167 (26.1%) PC + psychotropics. After 4 weeks, mean anxiety scores decreased by more than 7, 12 and 6 points (HAM-A, Spielberger State and Trait respectively), and SDS score by more than 4 points (JSS). CONCLUSION: Anxiety and/or SDS improved significantly in patients included on this study. PC could be an alternative to the use of psychotropic drugs for first intention treatment of anxiety and SDS. Further studies are needed to confirm those results. PMID- 26828003 TI - Bone computed tomography mineral content evaluation in chickens: effects of substances in homeopathic concentration. AB - METHODS: Ninety-six cobb race chickens were equally divided in 4 groups and randomly assigned to receive a standard treatment feed + homeopathic concentrations of Symphytum (S.) officinalis (9CH), or standard treatment feed + homeopathic concentrations of Tricalcarea (4CH), or standard treatment feed + homeopathic concentrations of Calcarea (C.) carbonica (30CH) or a placebo (the same feed but without any homeopathic compound) in order to assess the ability of the homeopathic compounds to increase the concentration of calcium hydroxyapatite in the sternal spongy bone tissue. We measured the concentration of calcium hydroxyapatite in the sternal spongy bone tissue of all chickens by means of a computed tomography (CT). RESULTS: 30%, 36% and 63% increase of sternum spongy bone mineralization was observed after a 2 years period in the treatment groups with S. officinalis (9CH), Tricalcarea (4CH) (*P < 0.05) and C. carbonica (30CH) (***P < 0.001) respectively. CONCLUSION: Bone mineralization is usually low in battery chickens reared in commercial poultry-sheds, creating a weakness of the whole animal supporting apparatus. Homeopathic preparations with bone-tissue tropism may improve their health quality. PMID- 26828004 TI - Effects of a dragonfly (Anax i.) homeopathic remedy on learning, memory and cell morphology in mice. AB - BACKGROUND: Homeopathy is a form of alternative medicine in which uses highly diluted preparations that are believed to cause healthy people to exhibit symptoms similar to those exhibited by patients. The aim of this study was to investigate the effects of dragonfly (Anax imperator, Anax i.) on learning and memory in naive mice using the Morris water maze (MWM) test; moreover, the effects of dragonfly on MK-801-induced cognitive dysfunction were evaluated. METHODS: Male balb-c mice were treated with dragonfly (30C and 200C) or MK-801 (0.2 mg/kg) alone or concurrently (n = 10). Dragonfly (D) and MK-801 were administered subchronically for 6 days intraperitoneally 60 min and 30 min, respectively, before the daily performance of the MWM test. RESULTS: This study revealed that in the familiarization session and first session of the MWM test, Anax i. D30 significantly decreased escape latency compared to the control group, although MK-801, D30 and D200 significantly increased escape latency at the end of five acquisition sessions. Anax i. combined with dizocilpine maleate (MK-801) also significantly decreased escape latency in the familiarization session and first session of the MWM test, although this combination increased escape latency compared to the MK-801 alone group at the end of the test. Time spent in escape platform's quadrant in the probe trial significantly decreased while mean distance to platform significantly increased in MK-801, D30 and D200 groups. In the MWM test, Anax i. combined with MK-801 significantly decreased speed of the animals compared to the MK-801 alone group. General cell morphology was disturbed in the MK-801 group while D30 and D200 seemed to improve cell damage in the MK 801 group. CONCLUSIONS: These results suggest that the homeopathic Anax i. can impair learning acquisition and reference memory, and it has beneficial effects on disturbed cell morphology. PMID- 26828005 TI - Use of homeopathy in organic dairy farming in Spain. AB - Organic farming principles promote the use of unconventional therapies as an alternative to chemical substances (which are limited by organic regulations), with homeopathy being the most extensive. Traditionally, Spain has had little faith in homeopathy but its use in organic farming is growing. Fifty-six Spanish organic dairy farmers were interviewed to obtain what we believe to be the first data on the use of homeopathy in organic dairy cattle in Spain. Only 32% of farms use some sort of alternative therapy (16.1% homeopathy, 10.7% phytotherapy and 5.3% using both therapies) and interestingly, a clear geographical pattern showing a higher use towards the East (similar to that in the human population) was observed. The main motivation to use homeopathy was the need to reduce chemical substances promoted by organic regulations, and the treatment of clinical mastitis being the principle reason. The number of total treatments was lower in farms using homeopathy compared with those applying allopathic therapies (0.13 and 0.54 treatments/cow/year respectively) and although the bulk SCC was significantly higher (p < 0.001) in these farms (161,826 and 111,218 cel/ml, respectively) it did not have any negative economical penalty for the farmer and milk quality was not affected complying with the required standards; on the contrary homeopathic therapies seems to be an alternative for reducing antibiotic treatments, allowing farmers to meet the organic farming principles. PMID- 26828006 TI - Inhalation therapy with M1 inhibits experimental melanoma development and metastases in mice. AB - BACKGROUND: M1 is a homeopathic medicine with immunostimulatory properties used mainly by cancer patients to complement current therapies. Metastatic melanoma is a skin-originated form of cancer without a single therapy able to produce high rate and sustained responses, which attracts the use of complementary therapies such as M1. However, M1's anti-melanoma effects remain to be pre-clinically demonstrated. Therefore in the present work, we utilized a pulmonary metastatic melanoma model and a subcutaneous melanoma growth model to investigate the potential benefits of treatment with M1. METHODS: C57BL/6 mice were injected intravenously or subcutaneously with B16F10 mouse melanoma cells. After 24 h, mice were treated with either M1 or vehicle (water) for 14 days, euthanized and harvested for multi-parameter pulmonary and tumor analyses. RESULTS: Mice treated with M1 had significantly lower tumor burden in the lungs and subcutaneous tissue than control mice. Furthermore, tumors were impaired in proliferation and tumor related angiogenesis by the inhibition of myeloid derived suppressor cells (MDSC) positive for angiotensin II type 1 receptor (AT1R). CONCLUSION: Altogether these data suggest M1 is an efficient candidate for melanoma therapy to be considered for future clinic studies as this study is the first supporting the idea that melanoma patients may benefit with the treatment. The treatment with M1 provides advantages considering the highly-diluted properties and a cost effective alternative to costly chemotherapeutic approaches with, if any, lower toxicity. PMID- 26828007 TI - Using hetero-isotherapics in cancer supportive care: the fruit of fifteen years of experience. AB - BACKGROUND: Chemotherapy, hormone therapy, and new targeted therapies for cancer lead to adverse effects which are often difficult to relieve using classical homeopathy. Besides diminishing the quality of life of the patient, they can force the oncologist to reduce or even to cease treatment prematurely, which represents a loss of opportunity for the patient. Faced with these recurring problems, would the use of homeopathic dilution of chemotherapy, also called hetero-isotherapy, be a suitable response for improving the tolerance of and the adherence to cancer treatment? METHODS: Based on experiments conducted for over 50 years by many authors, we have offered our patients, since 1998, a protocol of hetero-isotherapy chemotherapy starting the day after each cytotoxic infusion. It involves taking a daily dose of a dilution of the chemotherapy used, using the increased dilution technique from 5c to 15c. RESULTS: We observed a significant decrease in side effects, allergic reactions and late sequelae in the more than 6000 hetero-isotherapic treatments given to some 4000 patients. The better tolerance to chemotherapy and the improvement in quality of life led to an increase in treatment adherence. No interference with chemotherapy was observed. When it was necessary to prescribe another homeopathic medicine, combination with hetero-isotherapy generally improved its effectiveness. CONCLUSION: In a large population, followed for over 15 years, we observed that hetero-isotherapics, well tolerated and easy to use, reduced the side effects of chemotherapy, targeted therapy or hormone therapy, and so improve the quality of life of patients. PMID- 26828008 TI - NHMRC report on homeopathy; mixing apples with oranges. PMID- 26828009 TI - Scissors stab wound to the cervical spinal cord at the craniocervical junction. AB - BACKGROUND CONTEXT: Stab wounds resulting in spinal cord injury of the craniocervical junction are rare. A scissors stab wound to the cervical spinal cord has been reported only once in the literature. PURPOSE: This paper aimed to report a case of Brown-Sequard-plus syndrome in an 8-year-old boy secondary to a scissors stab wound at the craniocervical junction. STUDY DESIGN: Case report and review of the literature. PATIENT SAMPLE: Case report of an 8-year-old boy accidentally stabbed in the neck by scissors, which were thrown as a dart. METHODS: The case study of an 8-year-old boy who was hospitalized because of a scissors stab wound at the craniocervical junction. The patient developed Brown Sequard-plus syndrome on the left side of the body. Magnetic resonance imaging revealed a laceration of the spinal cord at the craniocervical junction with cerebrospinal fluid leakage. Careful cleansing and interrupted sutures of the wounds were performed to prevent cerebrospinal fluid leakage. Rehabilitation therapy was performed 2 days later. RESULTS: A follow-up examination revealed complete recovery of the neurologic deficit 8 months post-injury. CONCLUSION: Treatment of scissors stab wounds to the cervical spinal cord, whether conservative management or thorough surgical exploration, should be individualized based on history, examination, and imaging. As shown in this case report, despite conservative management, complete recovery, which was unexpected, was attributed to the initial mild laceration of the spinal cord and ipsilateral spinal cord functional compensation. PMID- 26828010 TI - Isolated spinal myeloid sarcoma with rapid progression. PMID- 26828011 TI - Where should a laminoplasty start? The effect of the proximal level on post laminoplasty loss of lordosis. AB - BACKGROUND CONTEXT: Open-door laminoplasty is a useful operation in the surgical management of cervical myelopathy with favorable outcomes and relatively low complications. One potential undesirable outcome is a decrease in cervical lordosis postoperatively. It is unknown whether the most proximal level undergoing laminoplasty affects the magnitude of loss of lordosis. PURPOSE: This study aimed to compare the loss of cervical lordosis postoperatively in patients for whom the most proximal level undergoing laminoplasty is C3 versus C4. STUDY DESIGN/SETTING: A retrospective radiographic review at an academic center was carried out. PATIENT SAMPLE: A total of 65 patients at a single institution who underwent plated open door laminoplasty for cervical myelopathy by multiple surgeons over a 5-year period were included. OUTCOME MEASURES: The primary outcome was change in cervical lordosis, which was the difference in C2-T1 Cobb angle between the postoperative and preoperative films. METHODS: Patients were divided into two groups based on the most proximal vertebral level undergoing laminoplasty. There were 49 patients who underwent laminoplasty beginning at C3, whereas 16 patients underwent laminoplasty beginning at C4. The C2-T1 Cobb angle was measured on the preoperative film and on the final postoperative follow-up film. The difference between these values was calculated for each patient, and the mean of the differences for the C3 group was compared with that of the C4 group. RESULTS: When C3 was the proximal plated laminoplasty level, loss of lordosis averaged 9 degrees . In contrast, when C4 was the proximal plated level, loss of lordosis was significantly less and averaged only 3 degrees (p=.047). In the group as a whole, mean preoperative lordosis was 18 degrees compared with 11 degrees postoperatively, for an overall 7 degrees loss of lordosis. CONCLUSIONS: Starting the laminoplasty at C4 led to significantly less loss of lordosis than starting at C3. When the pattern of spinal cord compression does not require laminoplasty at C3, consideration should be given to making C4 the most cephalad laminoplasty level rather than C3 to better preserve lordosis. PMID- 26828012 TI - Cancer Letters special issue hepatobiliary cancer featuring the guest editor. PMID- 26828014 TI - Radiogenomics - current status, challenges and future directions. AB - Radiogenomics designates a scientific field that addresses possible associations between genetic germline alterations and normal tissue toxicity after radiotherapy. The ultimate aim of this research is to establish a gene-based predictive test for normal tissue radiosensitivity. During the last 5 years, substantial progress has been achieved in this field. Several compelling associations for SNPs have been demonstrated in large candidate gene studies as well as genome wide association studies. These findings shed new light on radiobiology and expand our understanding of the processes that lead to side effects after radiotherapy. Despite this, certain fundamental challenges still relate to genomic approaches. Based on the latest insights into complex trait genetics and molecular genetics, we provide an analysis of these challenges and propose putative strategies to further advance the field. These strategies include 'big data approaches' and collaborative research within international consortia. Furthermore, research that combines the study of radiation-induced gene expression and genome-wide SNP genotype may discover genetic alterations that regulate the biological response to ionizing radiation. Thus, such integrative approaches may lead to genetic alterations that affect risk of normal tissue toxicity. PMID- 26828015 TI - mRNA export protein THOC5 as a tool for identification of target genes for cancer therapy. AB - Recent evidence indicates that mRNA export is selective, giving priority to a subset of mRNAs that control diverse biological processes including cell proliferation, differentiation, stress response, and cell survival as well as tumor development. The depletion of a member of the mRNA export complex, the THO complex, impairs the expression of only a subset of genes, but causes dramatic changes in phenotype, such as cell cycle inhibition, abnormal differentiation, and importantly apoptosis of stem cells and cancer cells but not normal epithelial cells, hepatocytes, or fibroblasts. Recent exosome sequence data revealed that over 100 driver gene mutations with a number of signaling pathways are involved in human cancer formation, indicating that multiple signaling pathways will need to be inhibited for cancer therapy. In this review we firstly describe a basic feature and function of the mRNA export complex, THO, secondly, the biological alteration upon depletion of a member of the THO complex in normal and cancer cells, and thirdly, identification of its target genes. Finally we describe our recent data on selection of targeting candidates from THOC5 dependent genes for application in cancer therapy. PMID- 26828013 TI - Regulation of prostate cancer progression by the tumor microenvironment. AB - Prostate cancer remains the most frequently diagnosed cancer in men in North America, and despite recent advances in treatment patients with metastatic disease continue to have poor five-year survival rates. Recent studies in prostate cancer have revealed the critical role of the tumor microenvironment in the initiation and progression to advanced disease. Experimental data have uncovered a reciprocal relationship between the cells in the microenvironment and malignant tumor cells in which early changes in normal tissue microenvironment can promote tumorigenesis and in turn tumor cells can promote further pro-tumor changes in the microenvironment. In the tumor microenvironment, the presence of persistent immune infiltrates contributes to the recruitment and reprogramming of other non-immune stromal cells including cancer-associated fibroblasts and a unique recently identified population of metastasis-initiating cells (MICs). These MICs, which can also be found as part of the circulating tumor cell (CTC) population in PC patients, promote cancer cell transformation, enhance metastatic potential and confer therapeutic resistance. MICs act can on other cells within the tumor microenvironment in part by secreting exosomes that reprogram adjacent stromal cells to create a more favorable tumor microenvironment to support continued cancer growth and progression. We review here the current data on the intricate relationship between inflammation, reactive stroma, tumor cells and disease progression in prostate cancer. PMID- 26828016 TI - MicroRNA-101-3p reverses gemcitabine resistance by inhibition of ribonucleotide reductase M1 in pancreatic cancer. AB - Pancreatic ductal adenocarcinoma (PDA) is among the most lethal malignancies and resistance to chemotherapy prevents the therapeutic outcome. MicroRNAs provide a novel therapeutic strategy. Here, the established and primary human PDA cell lines PANC-1, AsPC-1, MIA-PaCa2, AsanPaCa, BxPC-3 and three gemcitabine-resistant subclones were examined. A gene expression profiling revealed that the ribonucleotide reductase M1 (RRM1) was upregulated in gemcitabine-resistant cells, which was confirmed by qRT-PCR, Western blot analysis and immunostaining. Inhibition of RRM1 by lipotransfection of siRNA reduced its expression and reversed gemcitabine resistance. The expression of RRM1 correlated to gemcitabine resistance in vitro and was higher in malignant patient pancreas tissue compared to non-malignant pancreas tissue. By microRNA expression profiling, we identified microRNA-101-3p as top-downregulated candidate. Lipotransfection of microRNA-101 3p mimics inhibited the expression of RRM1, reduced the luciferase activity of its 3'UTR and sensitized for gemcitabine-induced cytotoxicity. These results underline the relevance of microRNA-101-3p-driven regulation of RRM1 in drug resistance and suggest the co-delivery of microRNA-101-3p and gemcitabine for more effective therapy outcome. PMID- 26828017 TI - Maribacter lutimaris sp. nov., isolated from marine sediment. AB - A Gram-staining-negative, moderately halophilic and strictly aerobic bacterium, designated strain KJ4T, was isolated from marine sediment at Gangjin in South Korea. Cells were catalase- and oxidase-positive long rods with gliding motility. Growth of strain KJ4T was observed at 4-37 degrees C (optimum, 15-25 degrees C), at pH 6.0-9.0 (optimum, pH 7.0-8.5) and in the presence of 1.0-7.0% (w/v) NaCl (optimum, 2.0-5.0%). Menaquinone 6 (MK-6) was the only isoprenoid quinone detected and iso-C15:0, iso-C17:0 3-OH, iso-C15:1 G and summed feature 3 (comprising C16:1omega7c and/or C16:1omega6c) were the major cellular fatty acids. The polar lipids of strain KJ4T consisted of phosphatidylethanolamine, an unidentified aminophospholipid and five unidentified lipids. The G+C content of the genomic DNA was 38.0 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain KJ4T formed a distinct phylogenetic lineage within the genus Maribacter. Strain KJ4T was most closely related to Maribacter orientalis KMM 3947T with 97.4% 16S rRNA gene sequence similarity. On the basis of phenotypic, chemotaxonomic and molecular features, strain KJ4T clearly represents a novel species of the genus Maribacter, for which the name Maribacter lutimaris sp. nov. is proposed. The type strain is KJ4T (=KACC 16438T=JCM 31154T). PMID- 26828018 TI - Host cell interactome of PA protein of H5N1 influenza A virus in chicken cells. AB - Influenza A virus (IAV) heavily depends on viral-host protein interactions in order to replicate and spread. Identification of host factors that interact with viral proteins plays crucial roles in understanding the mechanism of IAV infection. Here we report the interaction landscape of H5N1 IAV PA protein in chicken cells through the use of affinity purification and mass spectrometry. PA protein was expressed in chicken cells and PA interacting complexes were captured by co-immunoprecipitation and analyzed by mass spectrometry. A total of 134 proteins were identified as PA-host interacting factors. Protein complexes including the minichromosome maintenance complex (MCM), 26S proteasome and the coat protein I (COPI) complex associated with PA in chicken cells, indicating the essential roles of these functional protein complexes during the course of IAV infection. Gene Ontology and pathway enrichment analysis both showed strong enrichment of PA interacting proteins in the category of DNA replication, covering genes such as PCNA, MCM2, MCM3, MCM4, MCM5 and MCM7. This study has uncovered the comprehensive interactome of H5N1 IAV PA protein in its chicken host and helps to establish the foundation for further investigation into the newly identified viral-host interactions. BIOLOGICAL SIGNIFICANCE: Influenza A virus (IAV) is a great threat to public health and avian production. However, the manner in which avian IAV recruits the host cellular machinery for replication and how the host antagonizes the IAV infection was previously poorly understood. Here we present the viral-host interactome of the H5N1 IAV PA protein and reveal the comprehensive association of host factors with PA. PMID- 26828019 TI - Physical exercise, reactive oxygen species and neuroprotection. AB - Regular exercise has systemic beneficial effects, including the promotion of brain function. The adaptive response to regular exercise involves the up regulation of the enzymatic antioxidant system and modulation of oxidative damage. Reactive oxygen species (ROS) are important regulators of cell signaling. Exercise, via intensity-dependent modulation of metabolism and/or directly activated ROS generating enzymes, regulates the cellular redox state of the brain. ROS are also involved in the self-renewal and differentiation of neuronal stem cells and the exercise-mediated neurogenesis could be partly associated with ROS production. Exercise has strong effects on the immune system and readily alters the production of cytokines. Certain cytokines, especially IL-6, IL-1, TNF alpha, IL-18 and IFN gamma, are actively involved in the modulation of synaptic plasticity and neurogenesis. Cytokines can also contribute to ROS production. ROS mediated alteration of lipids, protein, and DNA could directly affect brain function, while exercise modulates the accumulation of oxidative damage. Oxidative alteration of macromolecules can activate signaling processes, membrane remodeling, and gene transcription. The well known neuroprotective effects of exercise are partly due to redox-associated adaptation. PMID- 26828020 TI - Effect of the SOD mimetic MnL4 on in vitro and in vivo oxaliplatin toxicity: Possible aid in chemotherapy induced neuropathy. AB - BACKGROUND: One of the most discomfortable dose-limiting adverse reactions of effective drugs for the treatment of solid tumors is a peripheral neuropathy which is the main reason for dose reduction and discontinuation of the therapy. We identified oxidative stress as one target of oxaliplatin toxicity in the search of possible adjuvant therapies to prevent neuropathy and alleviate pain. Therefore, we studied an effective SOD mimetic compound, MnL4, as a possible adjuvant treatment in in vitro cellular cultures and in vivo on a rat model of oxaliplatin-induced neuropathy. METHODS AND RESULTS: All rat manipulations were carried out according to the European Community guidelines for animal care. We performed experiments on SH-SY5Y, HT-29 and primary cortical rat astrocytes. Incubation with 100 uM oxaliplatin increased superoxide anion production and caspase 3/7 activity in the neuronal cell line SH-SY5Y and cortical astrocytes. MnL4 (10 uM) significantly reduced the increase in superoxide anion in both cell types, but prevented caspase 3/7 activity only in astrocytes. MnL4 reduced lipid peroxidation induced by oxaliplatin and normalized the intracellular calcium signal evoked by ATP and acetylcholine in astrocytes, preincubated with oxaliplatin. MnL4 did not interfere with the concentration- and time-dependent cytotoxic effects of oxaliplatin on the cancer cell lines HT-29 and LoVo. In vivo MnL4 reduced the response at mechanical noxious and mechanical and thermal non noxious stimuli in oxaliplatin treated animals. Rat rota-rod performances were improved. CONCLUSION: Since MnL4 exerts its beneficial effects without interfering with the anticancer activity of oxaliplatin, it could be proposed as adjuvant to prevent and reduce oxaliplatin induced neuropathy. PMID- 26828021 TI - Regulation of endothelial dynamics by PGC-1alpha relies on ROS control of VEGF-A signaling. AB - Peroxisome proliferator activated receptor gamma co-activator 1alpha (PGC-1alpha) is a regulator of mitochondrial metabolism and reactive oxygen species (ROS) that is known to play a relevant role in angiogenesis. AIMS: This study aims to investigate the role of ROS on the regulation by PGC-1alpha of angiogenesis. METHODS AND RESULTS: We found that endothelial cells (ECs) from mice deleted for PGC-1alpha display attenuated adhesion to the extracellular matrix, together with slower and reversible spreading. Structural analysis demonstrates unstable formation of focal adhesions, defective cytoskeleton reorganization in response to cellular matrix adhesion, cell migration and cell-cell adhesion. Confluent cultures showed also a reduction of membrane bound VE-cadherin, suggesting defective inter-cellular junction formation. Functional consequences included impaired directional migration, and enhanced tip phenotype in aortic explants sprouting assays. At the molecular level, PGC-1alpha-deleted ECs exhibit a constitutive activation of the vascular endothelial growth factor-A (VEGF-A) signaling pathway and a defective response to VEGF-A. All these alterations are partially reversed by administration of the antioxidant EUK-189. The contribution of mitochondrial ROS and NOX activation was confirmed using a mitochondrial targeted antioxidant (MitoTEMPO) and a NOX inhibitor (VAS-2870). These results indicate that elevated production of ROS in the absence of PGC-1alpha is a key factor in the alteration of the VEGF-A signaling pathway and the capacity of endothelial cells to form stable interactions with other endothelial cells and with the extracellular matrix. Our findings show that PGC-1alpha control of ROS homeostasis plays an important role in the control of endothelial response to VEGF-A. PMID- 26828022 TI - Terasakiella brassicae sp. nov., isolated from the wastewater of a pickle processing factory, and emended descriptions of Terasakiella pusilla and the genus Terasakiella. AB - A Gram-stain-negative, motile, polyhydroxybutyrate-accumulating, aerobic, S shaped bacterium, designated B3T, was isolated from the wastewater of a pickle processing factory. 16S rRNA gene sequence similarity analysis showed that it was most closely related to the type strain, Terasakiella pusilla (96.6% similarity). Strain B3T was able to grow at 4-40 degrees C (optimum 32-37 degrees C), pH 5.5 9.0 (optimum 6.5-7.5) and with 0.5-8% (w/v) NaCl present (optimum 1-2%, w/v). Chemotaxonomic analysis showed that the respiratory quinone was ubiquinone Q-10, the major fatty acids included C16:0, C18:1omega7c and C16:1omega7c and/or iso C15:2-OH. The major polar lipids included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylserine, aminophospholipid and three uncharacterized phospholipids. The genomic DNA G+C content of strain B3T was 42.3 mol%. The DNA-DNA relatedness value between B3T and T. pusilla DSM 9263T was 23.9%. On the basis of the phenotypic, chemotaxonomic and genotypic characteristics of strain B3T, it represents a novel species of the genus Terasakiella, for which the name Terasakiella brassicae sp. nov. is proposed. The type strain is B3T (=KCTC 42652T=CGMCC 1.15254T). Emended descriptions of T. pusilla and the genus Terasakiella are also presented. PMID- 26828023 TI - Dinghuibacter silviterrae gen. nov., sp. nov., isolated from forest soil. AB - A novel Gram-stain negative, non-motile, rod-shaped, aerobic bacterial strain, designated DHOA34T, was isolated from forest soil of Dinghushan Biosphere Reserve, Guangdong Province, China. Comparative 16S rRNA gene sequence analysis showed that it exhibited highest similarity with Flavisolibacter ginsengiterrae Gsoil 492T and Flavitalea populi HY-50RT, at 90.89 and 90.83%, respectively. In the neighbour-joining phylogenetic tree based on 16S rRNA gene sequences, DHOA34T formed an independent lineage within the family Chitinophagaceae but was distinct from all recognized species and genera of the family. The major cellular fatty acids of DHOA34T included iso-C15:0, anteiso-C15:0, iso-C17:0 3-OH and summed feature 3 (C16:1omega6c and/or C16:1omega7c). The DNA G+C content was 51.6 mol% and the predominant quinone was menaquinone 7 (MK-7). Flexirubin pigments were produced. The phenotypic, chemotaxonomic and phylogenetic data demonstrate consistently that strain DHOA34T represents a novel species of a new genus in the family Chitinophagaceae, for which the name Dinghuibacter silviterrae gen. nov., sp. nov. is proposed. The type strain of Dinghuibacter silviterrae is DHOA34T (=CGMCC 1.15023T=KCTC 42632T). PMID- 26828024 TI - Inhibition by blueberries (bilberries) and extract from milk thistle of rat forestomach hyperplasia induced by oral smokeless tobacco (Swedish snus). AB - The aim of this study was to identify palatable additives which have a significant protective action against soft tissue changes in the oral cavity caused by Swedish smokeless tobacco ("snus"), and that satisfy existing legal requirements. Although the cancer risk from snus is extremely low, long term use may result in highly undesirable keratotic lesions and associated epithelial abnormalities in the oral cavity. The rat forestomach, which is vulnerable to the irritative action of non-genotoxic compounds like butylated hydroxyanisole, propionic acid as well as snus, was chosen as an experimental model. Studied toxicological endpoints included histopathology and cellular proliferation based on DNA incorporation of bromodeoxyuridine. After 6 weeks' exposure, blueberries (bilberries) and an extract from the common milk thistle were found to exert a highly significant inhibition of cell proliferation induced by snus in the rat forestomach epithelium, indicating a potential protection with respect soft tissue changes in the human oral cavity. PMID- 26828026 TI - New Year address from Zoological Research. PMID- 26828025 TI - A high dose mode of action for tetrabromobisphenol A-induced uterine adenocarcinomas in Wistar Han rats: A critical evaluation of key events in an adverse outcome pathway framework. AB - TBBPA is a non-genotoxic flame retardant used to improve fire safety in a wide variety of consumer products. Estimated human exposures to TBBPA are very low (<0.000084 mg/kg-day), relative to the doses (500 and 1000 mg/kg-day of TBBPA) administered in a recent bioassay that resulted in uterine tumors in Wistar Han rats following chronic exposure. As part of an effort to characterize the relevance of the uterine tumors to humans, data and biological knowledge relevant to the progression of events associated with TBBPA-induced uterine tumors in female rats were organized in an adverse outcome pathway (AOP) framework. Based on a review of possible MOAs for chemically induced uterine tumors and available TBBPA data sets, a plausible molecular initiating event (MIE) was the ability of TBBPA to bind to and inhibit estrogen sulfotransferases, the enzymes responsible for sulfation of estradiol. Subsequent key events in the AOP, including increased bioavailability of unconjugated estrogens in uterine tissue, would occur as a result of decreased sulfation, leading to a disruption in estrogen homeostasis, increased expression of estrogen responsive genes, cell proliferation, and hyperplasia. Available data support subsequent key events, including generation of reactive quinones from the metabolism of estrogens, followed by DNA damage that could contribute to the development of uterine tumors. Uncertainties associated with human relevance are highlighted by potential strain/species sensitivities to development of uterine tumors, as well as the characterization of a dose-dependent MIE. For the latter, it was determined that the TBBPA metabolic profile is altered at high doses (such as those used in the cancer bioassay), and thus an MIE that is only operative under repeated high dose, administration. The MIE and subsequent key events for the development of TBBPA induced uterine tumors are not feasible in humans given differences in the kinetic and dynamic factors associated with high dose exposures in rats relative to human exposure levels to TBBPA. PMID- 26828027 TI - A new resource for China. PMID- 26828028 TI - Advances in herpetological research emanating from China. PMID- 26828029 TI - The Australasian frog family Ceratobatrachidae in China, Myanmar and Thailand: discovery of a new Himalayan forest frog clade. AB - In an effort to study the systematic affinities and specieslevel phylogenetic relationships of the enigmatic anurans variably assigned to the genera Ingerana or Limnonectes (family Dicroglossidae), we collected new molecular sequence data for five species including four Himalayan taxa, Limnonectes xizangensis, Lim. medogensis, Lim. alpina, [corrected] Ingerana borealis and one southeast Asian species, I. tasanae, and analyzed these together with data from previous studies involving other ostensibly related taxa. Our surprising results demonstrate unequivocally that Lim. xizangensis, Lim. medogensis and Lim. alpina [corrected] form a strongly supported clade, the sister-group of the family Australasian forest frog family Ceratobatrachidae. This discovery requires an expansion of the definition of Ceratobatrachidae and represents the first record of this family in China. These three species are distinguished from the species of Ingerana and Limnonectes by the: (1) absence of interdigital webbing of the foot, (2) absence of terminal discs on fingers and toes, (3) absence of circumarginal grooves on the fingers and toes, and (4) absence of tarsal folds. Given their phylogenetic and morphological distinctiveness, we assign them to the oldest available generic name for this clade, Liurana Dubois 1987, and transfer Liurana from Dicroglossidae to the family Ceratobatrachidae. In contrast, Ingerana tasanae was found to be clustered with strong support with the recently described genus Alcalus (Ceratobatrachidae), a small clade of otherwise Sundaic species; this constitutes a new record of the family Ceratobatrachidae for Myanmar and Thailand. Finally, Ingerana borealis clustered with the "true" Ingerana (family Dicroglossidae), for which the type species is I. tenasserimensis. PMID- 26828030 TI - A new genus and species of treefrog from Medog, southeastern Tibet, China (Anura, Rhacophoridae). AB - A new genus and species of threefrog is described from Medog, southeastern Tibet, China based on morphological and phylogenetic data. The new genus can be distinguished from other treefrog genera by the following combination of characters: (1) body size moderate, 45.0 mm in male; (2) snout rounded; (3) canthus rostralis obtuse and raised prominently, forming a ridge from nostril to anterior corner of eyes; (4) web rudimentary on fingers; (5) web moderately developed on toes; (6) phalange "Y" shaped, visible from dorsal side of fingers and toes; (7) skin of dorsal surfaces relatively smooth, scatted with small tubercles; (8) iris with a pale yellow, "X" shaped pattern of pigmentation. PMID- 26828031 TI - A new species of the genus Scutiger (Anura: Megophryidae) from Medog of southeastern Tibet, China. AB - A new species of Scutiger Theobald, 1868 is described from Medog, southeastern Tibet, China, based on morphological and molecular data. The new species was previously identified as Scutiger nyingchiensis, but it can be differentiated from the latter and all other congeners by the following combination of characters: (1) medium adult body size, SVL 50.5-55.6 mm in males and 53.8-57.2 mm in females; (2) maxillary teeth absent; (3) web rudimentary between toes; (4) prominent, conical-shaped tubercles on dorsal and lateral surfaces of body and limbs; (5) tubercles covered by black spines in both sexes in breeding condition; (6) a pair of pectoral glands and a pair of axillary glands present and covered by black spines in males in breeding condition, width of axillary gland less than 50% of pectoral gland; (7) nuptial spines present on dorsal surface of first and second fingers, and inner side of third finger in males in breeding condition; (8) spines absent on the abdominal region; (9) vocal sac absent. In addition, the distribution and conservation status of the new species are also discussed. PMID- 26828032 TI - A new species of the genus Amolops (Amphibia: Ranidae) from southeastern Tibet, China. AB - A new species of the genus Amolops Cope, 1865 is described from Nyingchi, southeastern Tibet, China, based on morphological and molecular data. The new species, Amolops nyingchiensis sp. nov. is assigned to the Amolops monticola group based on its skin smooth, dorsolateral fold distinct, lateral side of head black, upper lip stripe white extending to the shoulder. Amolops nyingchiensis sp. nov. is distinguished from all other species of Amolops by the following combination of characters: (1) medium body size, SVL 48.5-58.3 mm in males, and 57.6-70.7 mm in females; (2) tympanum distinct, slightly larger than one third of the eye diameter; (3) a small tooth-like projection on anteromedial edge of mandible; (4) the absence of white spine on dorsal surface of body; (5) the presence of circummarginal groove on all fingers; (6) the presence of vomerine teeth; (7) background coloration of dorsal surface brown, lateral body gray with yellow; (8) the presence of transverse bands on the dorsal limbs; (9) the presence of nuptial pad on the first finger in males; (10) the absence of vocal sac in males. Taxonomic status of the populations that were previously identified to A. monticola from Tibet is also discussed. PMID- 26828034 TI - AmphibiaChina: an online database of Chinese Amphibians. AB - AmphibiaChina, an open-access, web-based database, is designed to provide comprehensive and up-to-date information on Chinese amphibians. It offers an integrated module with six major sections. Compared to other known databases including AmphibiaWeb and Amphibian Species of the World, AmphibiaChina has the following new functions: (1) online species identification based on DNA barcode sequences; (2) comparisons and discussions of different major taxonomic systems; and (3) phylogenetic progress on Chinese amphibians. This database offers a window for the world to access available information of Chinese amphibians. AmphibiaChina with its Chinese version can be accessed at http://www.amphibiachina.org. PMID- 26828033 TI - Two new species of Japalura (Squamata: Agamidae) from the Hengduan Mountain Range, China. AB - Until recently, the agamid species, Japalura flaviceps, was recognized to have the widest geographic distribution among members of the genus occurring in China, from eastern Tibet to Shaanxi Province. However, recent studies restricted the distribution of J. flaviceps to the Dadu River valley only in northwestern Sichuan Province, suggesting that records of J. flaviceps outside the Dadu River valley likely represent undescribed diversity. During two herpetofaunal surveys in 2013 and 2015, eight and 12 specimens of lizards of the genus Japalura were collected from the upper Nujiang (=Salween) Valley in eastern Tibet, China, and upper Lancang (=Mekong) Valley in northwestern Yunnan, China, respectively. These specimens display a unique suite of diagnostic morphological characters. Our robust comparisons of phenotype reveal that these populations can be distinguished readily from J. flaviceps and all other recognized congeners. Herein, we describe the two Japalura lineages as new species, Japalura laeviventris sp. nov. and Japalura iadina sp. nov.. In addition, we provide updated conservation assessments for the new species as well as imperiled congeners according to the IUCN criteria for classification, discuss the importance of color patterns in the diagnosis and description of species in the genus Japalura, and discuss directions for future taxonomic studies of the group. PMID- 26828035 TI - Niastella vici sp. nov., isolated from farmland soil. AB - Strain DJ57T is a Gram-reaction-negative, filamentous-shaped, non-flagellated, aerobic bacterium isolated from farmland soil in Hunan province of China. 16S rRNA gene sequence analysis demonstrated that this isolate belonged to the genus Niastella, with 95.83% nucleotide identity to Niastella populi THYL-44T, while the similarities to other type strains of species of the genus Niastella were less than 95.76%. The major isoprenoid quinone was menaquinone-7 and the major fatty acids (>5%) were iso-C15:0, iso-C17:0 3-OH, iso-C15:1 G, anteiso-C15:0 and iso-C16:0. The DNA G+C content was 44 mol%. Polar lipids were phosphatidylethanolamine, three unknown aminophospholipids, three unknown phospholipids and six unknown lipids. The chemotaxonomic, phenotypic and genotypic data indicated that strain DJ57T represents a novel species of the genus Niastella, for which the name Niastella vici sp. nov. is proposed. The type strain is DJ57T (=KCTC 42474T=CCTCC AB 2015052T). PMID- 26828037 TI - Obesity, metabolic profile, and inhibition failure: Young women under scrutiny. AB - BACKGROUND: The prevalence of obesity, as well as evidence about this pathology as a risk factor for cognitive decline and dementia in the elderly, is increasing worldwide. Executive functions have been found to be compromised in most studies, although the specific results are dissimilar. Obese young women constitute an interesting study and intervention group, having been found to be unaffected by age and hormonal negative effects on cognition and considering that their health problems affect not only themselves but their families and offspring. The objective of the present study was to compare the executive performance of obese young women with that of a healthy control group. METHODS: A cross-sectional study was done among premenopausal women from a public hospital in Buenos Aires. The sample comprised 113 participants (32 healthy controls and 81 obese women), who were evaluated for depressive and anxiety symptoms (Beck Depression Inventory II and State-Trait Anxiety Inventory) and executive functioning (Trail-Making Test B, Stroop Color and Word Test, Wisconsin Card Sorting Test, and verbal fluency test). Statistical analysis was done by using the SPSS version 20.0 software. RESULTS: Among executive functions, a significant difference was found between groups in inhibition (p<0.01). No correlation was found between psychopathologic measures and Stroop Test Interference results. We found slight correlations between Stroop Test Interference results, waist circumference, fat mass and HDL-cholesterol. In obese group, there was a negative slightly correlation between this cognitive test and 2h post-load glucose level. CONCLUSIONS: Inhibition was decreased in our obese young women group, and glucose/lipid metabolism may be involved in this association. The cognitive impairment is comparable with that described in addictive conditions. Our conclusions support the concept of multidisciplinary management of obese patients from the time of diagnosis. Detecting and understanding cognitive dysfunction in this population is essential to providing appropriate treatment. PMID- 26828038 TI - Sex-specific effects of daily exposure to sucrose on spatial memory performance in male and female rats, and implications for estrous cycle stage. AB - Excessive consumption of sugar sweetened drinks is proposed to produce functional changes in the hippocampus, leading to perturbations in learning and memory. In this study we examined the impact of 2h daily access to 10% sucrose (or no sucrose in controls) on recognition memory tasks in young male and female rats. In Experiment 1 we tested rats on memory tasks reliant on the hippocampus (place recognition), perirhinal cortex (object recognition), and a combination of hippocampus, prefrontal cortex and perirhinal cortex (object-in-place memory). Exposure to sucrose for 2h a day for 14days prior to behavioral testing did not affect object recognition, but impaired spatial memory to an extent in both male and female rats. Male rats exposed to sucrose were impaired at both place recognition and object-in-place recognition, however female rats showed no impairment in object-in-place performance. Plasticity within the hippocampus is known to increase during the proestrus phase of the estrous cycle and is related to higher levels of circulating estrogens. In Experiment 2 we tested place recognition and object-in-place memory in 10% sucrose exposed or non-exposed control female rats both during the metestrus (low estrogen) and proestrus (high estrogen) phases of their cycle on place recognition and object-in-place memory. Both sucrose exposed and control female rats were able to perform place object-in place recognition correctly during metestrus and proestrus, however sucrose exposed rats were only able to perform place recognition correctly during proestrus. This indicates that when hippocampal function is compromised, endogenous estrogens may boost memory performance in females, and that males may be at more risk of high sugar diet induced cognitive deficits. PMID- 26828039 TI - SOCS3 expression within leptin receptor-expressing cells regulates food intake and leptin sensitivity but does not affect weight gain in pregnant mice consuming a high-fat diet. AB - Pregnancy induces transitory metabolic changes including increases in food intake and body fat deposition, as well as leptin and insulin resistance. Recent findings have suggested that increased hypothalamic expression of suppressor of cytokine signaling-3 (SOCS3) is a key mechanism responsible for triggering those metabolic adaptations. Because obesity is a risk factor for gestational metabolic imbalances, we aimed to study the role of SOCS3 during pregnancy in obese mice. Female mice carrying a deletion of SOCS3 in leptin receptor-expressing cells (SOCS3 KO mice) were exposed to a chronic high-fat diet (HFD), and we then studied their energy balance and glucose homeostasis during pregnancy. SOCS3 deletion did not prevent diet-induced obesity or changes in body weight and adiposity observed during pregnancy. However, the typical increase in food intake during mid- and late-pregnancy was blunted in SOCS3 KO females. We also observed a slight improvement in glucose homeostasis and increased leptin sensitivity in the arcuate nucleus of the hypothalamus in pregnant SOCS3 KO mice on HFD. Despite this, SOCS3 KO mice had an increased number of uterine reabsorptions and fewer fetuses compared to the controls. Compared to control animals, a reduction in proopiomelanocortin and an increase in oxytocin mRNA levels were observed in the hypothalamus of pregnant SOCS3 KO mice. In contrast to previous studies using lean animals, conditional SOCS3 ablation did not prevent major gestational metabolic changes in diet-induced obese mice. Our findings contribute to the understanding of the role of SOCS3 in mediating pregnancy-induced metabolic adaptations. PMID- 26828042 TI - Chronic diseases like asthma and COPD: do they truly exist? PMID- 26828043 TI - Asthma phenotypes in childhood: conceptual thoughts on stability and transition. PMID- 26828044 TI - Stressful sleep. PMID- 26828045 TI - Incidence of venous thromboembolism in COPD: linking inflammation and thrombosis? PMID- 26828046 TI - Optimising treatment for post-operative lung cancer recurrence. PMID- 26828047 TI - Ageing lungs and very elderly COPD: anytime and anywhere. PMID- 26828048 TI - The bronchiectasis severity index and FACED score for bronchiectasis. PMID- 26828049 TI - Treating allergic bronchopulmonary aspergillosis: the way forward. PMID- 26828050 TI - Genetic testing in pulmonary hypertension: how should our clinical practice reflect recent advances? PMID- 26828051 TI - Sex differences in pulmonary hypertension: are we cleaning up the mess? PMID- 26828052 TI - Bedaquiline and multidrug-resistant tuberculosis: a systematic and critical analysis of the evidence. PMID- 26828053 TI - European IPF Patient Charter: an SOS to the world. PMID- 26828054 TI - Prenatal stress and childhood asthma risk: taking a broader view. PMID- 26828055 TI - Treatable traits: toward precision medicine of chronic airway diseases. AB - Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent chronic airway diseases that have a high personal and social impact. They likely represent a continuum of different diseases that may share biological mechanisms (i.e. endotypes), and present similar clinical, functional, imaging and/or biological features that can be observed (i.e. phenotypes) which require individualised treatment. Precision medicine is defined as "treatments targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic, or psychosocial characteristics that distinguish a given patient from other patients with similar clinical presentations". In this Perspective, we propose a precision medicine strategy for chronic airway diseases in general, and asthma and COPD in particular. PMID- 26828056 TI - End TB with precision treatment! PMID- 26828057 TI - beta-blockers in pulmonary arterial hypertension: generation might matter. PMID- 26828058 TI - Cameroon's MDR-TB treatment programme jeopardised by cross-border migration. PMID- 26828059 TI - Cameroon's multidrug-resistant tuberculosis treatment programme jeopardised by cross-border migration. PMID- 26828060 TI - Is there hope of improving the prognosis of pulmonary tumour thrombotic microangiopathy? PMID- 26828062 TI - "Cladribine improves lung cysts and pulmonary function in a child with histiocytosis." Ralph Epaud, Hubert Ducou Le Pointe, Sylvie Fasola, Sandra Ploussard, Celine Delestrain, Chiara Sileo and Jean Donadieu. Eur Respir J 2015; 45: 831-833. PMID- 26828061 TI - Earlier diagnosis and international registries may improve outcomes in pulmonary tumour thrombotic microangiopathy. PMID- 26828063 TI - ERJ February Podcast: precision medicine in chronic airway diseases. PMID- 26828064 TI - Small Intestine but Not Liver Lysophosphatidylcholine Acyltransferase 3 (Lpcat3) Deficiency Has a Dominant Effect on Plasma Lipid Metabolism. AB - Lysophosphatidylcholine acyltransferase 3 (Lpcat3) is involved in phosphatidylcholine remodeling in the small intestine and liver. We investigated lipid metabolism in inducible intestine-specific and liver-specificLpcat3gene knock-out mice. We producedLpcat3-Flox/villin-Cre-ER(T2)mice, which were treated with tamoxifen (at days 1, 3, 5, and 7), to deleteLpcat3specifically in the small intestine. At day 9 after the treatment, we found that Lpcat3 deficiency in enterocytes significantly reduced polyunsaturated phosphatidylcholines in the enterocyte plasma membrane and reduced Niemann-Pick C1-like 1 (NPC1L1), CD36, ATP binding cassette transporter 1 (ABCA1), and ABCG8 levels on the membrane, thus significantly reducing lipid absorption, cholesterol secretion through apoB dependent and apoB-independent pathways, and plasma triglyceride, cholesterol, and phospholipid levels, as well as body weight. Moreover, Lpcat3 deficiency does not cause significant lipid accumulation in the small intestine. We also utilized adenovirus-associated virus-Cre to depleteLpcat3in the liver. We found that liver deficiency only reduces plasma triglyceride levels but not other lipid levels. Furthermore, there is no significant lipid accumulation in the liver. Importantly, small intestine Lpcat3 deficiency has a much bigger effect on plasma lipid levels than that of liver deficiency. Thus, inhibition of small intestine Lpcat3 might constitute a novel approach for treating hyperlipidemia. PMID- 26828065 TI - A Novel Inositol Pyrophosphate Phosphatase in Saccharomyces cerevisiae: Siw14 PROTEIN SELECTIVELY CLEAVES THE beta-PHOSPHATE FROM 5-DIPHOSPHOINOSITOL PENTAKISPHOSPHATE (5PP-IP5). AB - Inositol pyrophosphates are high energy signaling molecules involved in cellular processes, such as energetic metabolism, telomere maintenance, stress responses, and vesicle trafficking, and can mediate protein phosphorylation. Although the inositol kinases underlying inositol pyrophosphate biosynthesis are well characterized, the phosphatases that selectively regulate their cellular pools are not fully described. The diphosphoinositol phosphate phosphohydrolase enzymes of the Nudix protein family have been demonstrated to dephosphorylate inositol pyrophosphates; however, theSaccharomyces cerevisiaehomolog Ddp1 prefers inorganic polyphosphate over inositol pyrophosphates. We identified a novel phosphatase of the recently discovered atypical dual specificity phosphatase family as a physiological inositol pyrophosphate phosphatase. Purified recombinant Siw14 hydrolyzes the beta-phosphate from 5-diphosphoinositol pentakisphosphate (5PP-IP5or IP7)in vitro. In vivo,siw14Delta yeast mutants possess increased IP7levels, whereas heterologousSIW14overexpression eliminates IP7from cells. IP7levels increased proportionately whensiw14Delta was combined withddp1Delta orvip1Delta, indicating independent activity by the enzymes encoded by these genes. We conclude that Siw14 is a physiological phosphatase that modulates inositol pyrophosphate metabolism by dephosphorylating the IP7isoform 5PP-IP5to IP6. PMID- 26828066 TI - Mit1 Transcription Factor Mediates Methanol Signaling and Regulates the Alcohol Oxidase 1 (AOX1) Promoter in Pichia pastoris. AB - The alcohol oxidase 1 (AOX1) promoter (P AOX1) of Pichia pastoris is the most powerful and commonly used promoter for driving protein expression. However, mechanisms regulating its transcriptional activity are unclear. Here, we identified a Zn(II)2Cys6-type methanol-induced transcription factor 1 (Mit1) and elucidated its roles in regulating PAOX1 activity in response to glycerol and methanol. Mit1 regulated the expression of many genes involved in methanol utilization pathway, including AOX1, but did not participate in peroxisome proliferation and transportation of peroxisomal proteins during methanol metabolism. Structural analysis of Mit1 by performing domain deletions confirmed its specific and critical role in the strict repression of P AOX1 in glycerol medium. Importantly, Mit1, Mxr1, and Prm1, which positively regulated P AOX1 in response to methanol, were bound to P AOX1 at different sites and did not interact with each other. However, these factors cooperatively activated P AOX1 through a cascade. Mxr1 mainly functioned during carbon derepression, whereas Mit1 and Prm1 functioned during methanol induction, with Prm1 transmitting methanol signal to Mit1 by binding to the MIT1 promoter (P MIT1), thus increasingly expressing Mit1 and subsequently activating P AOX1. PMID- 26828069 TI - Federal Funding to Address the Health Needs of Persons With Mental Disorders: Why Is This Population a Special Case? PMID- 26828067 TI - Group X Secreted Phospholipase A2 Releases omega3 Polyunsaturated Fatty Acids, Suppresses Colitis, and Promotes Sperm Fertility. AB - Within the secreted phospholipase A2(sPLA2) family, group X sPLA2(sPLA2-X) has the highest capacity to hydrolyze cellular membranes and has long been thought to promote inflammation by releasing arachidonic acid, a precursor of pro inflammatory eicosanoids. Unexpectedly, we found that transgenic mice globally overexpressing human sPLA2-X (PLA2G10-Tg) displayed striking immunosuppressive and lean phenotypes with lymphopenia and increased M2-like macrophages, accompanied by marked elevation of free omega3 polyunsaturated fatty acids (PUFAs) and their metabolites. Studies usingPla2g10-deficient mice revealed that endogenous sPLA2-X, which is highly expressed in the colon epithelium and spermatozoa, mobilized omega3 PUFAs or their metabolites to protect against dextran sulfate-induced colitis and to promote fertilization, respectively. In colitis, sPLA2-X deficiency increased colorectal expression of Th17 cytokines, and omega3 PUFAs attenuated their production by lamina propria cells partly through the fatty acid receptor GPR120. In comparison, cytosolic phospholipase A2(cPLA2alpha) protects from colitis by mobilizing omega6 arachidonic acid metabolites, including prostaglandin E2 Thus, our results underscore a previously unrecognized role of sPLA2-X as an omega3 PUFA mobilizerin vivo, segregated mobilization of omega3 and omega6 PUFA metabolites by sPLA2-X and cPLA2alpha, respectively, in protection against colitis, and the novel role of a particular sPLA2-X-driven PUFA in fertilization. PMID- 26828068 TI - Population and assay thresholds for the predictive value of lipoprotein (a) for coronary artery disease: the EPIC-Norfolk Prospective Population Study. AB - Variable agreement exists between different lipoprotein (a) [Lp(a)] measurement methods, but their clinical relevance remains unclear. The predictive value of Lp(a) measured by two different assays [Randox and University of California, San Diego (UCSD)] was determined in 623 coronary artery disease (CAD) cases and 948 controls in a case-control study within the EPIC-Norfolk Prospective Population Study. Participants were divided into sex-specific quintiles, and by Lp(a) <50 versus ~50 mg/dl, which represents the 80th percentile in northern European subjects. Randox and UCSD Lp(a) levels were strongly correlated; Spearman's correlation coefficients for men, women, and sexes combined were 0.905, 0.915, and 0.909, respectively (P< 0.001 for each). The >80th percentile cutoff values, however, were 36 mg/dl and 24 mg/dl for the Randox and UCSD assays, respectively. Despite this, Lp(a) levels were significantly associated with CAD risk, with odds ratios of 2.18 (1.58-3.01) and 2.35 (1.70-3.26) for people in the top versus bottom Lp(a) quintile for the Randox and UCSD assays, respectively. This study demonstrates that CAD risk is present at lower Lp(a) levels than the currently suggested optimal Lp(a) level of <50 mg/dl. Appropriate thresholds may need to be population and assay specific until Lp(a) assays are standardized and Lp(a) thresholds are evaluated broadly across all populations at risk for CVD and aortic stenosis. PMID- 26828070 TI - A Tribute to Chris Marshall. PMID- 26828071 TI - Can you feel the real paper? PMID- 26828072 TI - Costs and Utilization of Operating Rooms in a Public Hospital in Trinidad, West Indies. AB - CONTEXT: A top-down evaluation of the costs of operating rooms (ORs) is not commonly done because it is relevant mostly in a publicly funded system. OBJECTIVE: This study was conducted to determine the costs and utilization of ORs in a public hospital in Trinidad, West Indies, for two one-year periods using a top-down model. DESIGN: Quantitative observational study.Main Outcome Measures: A "cost-block" model suggested for evaluation of intensive care unit costs was adapted to suit ORs. Data were obtained from personal interviews, records, and surveys from the appropriate hospital departments. Adjusted OR utilization times also were recorded for both years. RESULTS: The total annual costs of 4 ORs for the years 2006 and 2009 were approximately US $2.2 and $3.2 million, respectively. Capital expenditure contributed to 70% of the costs, followed by consumables (15%) and medical staff salary (8%). The daily cost of running the ORs was US $6242 in 2006, which rose to $8873 in 2009. The cost of unutilized OR time was approximately US $298,342 in 2006 and was reduced to $198,315 during 2009. CONCLUSION: The adapted cost-block model was useful to evaluate the costs of ORs in a public hospital in Trinidad and can be used from the government's expenditure perspective. Because the cost of running the ORs was high, efficiency must be improved to minimize waste. PMID- 26828073 TI - An Unusual Presentation of Dengue Fever: Association with Longitudinal Extensive Transverse Myelitis. AB - Association of dengue fever with transverse myelitis in the form of extensive spinal cord involvement is a rare entity described in the literature. We describe a middle-aged man who presented with dengue fever and in whom weakness of the bilateral lower limbs and urinary incontinence developed on the third day of fever. Magnetic resonance imaging confirmed the diagnosis of longitudinally extensive transverse myelitis. Over a four-week course of corticosteroids with supportive management, the patient recovered without any residual neurologic deficit. PMID- 26828074 TI - ECG Diagnosis: Isolated Posterior Wall Myocardial Infarction. PMID- 26828075 TI - Isolated Pancreatic Histoplasmosis: An Unusual Suspect of Pancreatic Head Mass in an Immunocompetent Host. AB - Histoplasmosis is endemic to the Mississippi and Ohio River valley regions in the US. It usually affects patients with underlying immunodeficiency but can also be seen in immunocompetent hosts. Although gastrointestinal involvement is common in the setting of disseminated histoplasmosis, isolated gastrointestinal involvement is uncommon. We report a case of isolated pancreatic histoplasmosis in an immunocompetent patient, presenting as painless jaundice and pancreatic head mass. PMID- 26828076 TI - Caring Science: Transforming the Ethic of Caring-Healing Practice, Environment, and Culture within an Integrated Care Delivery System. AB - In early 2010, leaders within Kaiser Permanente (KP) Northern California's Patient Care Services division embarked on a journey to embrace and embed core tenets of Caring Science into the practice, environment, and culture of the organization. Caring Science is based on the philosophy of Human Caring, a theory articulated by Jean Watson, PhD, RN, AHN-BC, FAAN, as a foundational covenant to guide nursing as a discipline and a profession. Since 2010, Caring Science has enabled KP Northern California to demonstrate its commitment to being an authentic person- and family-centric organization that promotes and advocates for total health. This commitment empowers KP caregivers to balance the art and science of clinical judgment by considering the needs of the whole person, honoring the unique perception of health and healing that each member or patient holds, and engaging with them to make decisions that nurture their well-being. The intent of this article is two-fold: 1) to provide context and background on how a professional practice framework was used to transform the ethic of caring healing practice, environment, and culture across multiple hospitals within an integrated delivery system; and 2) to provide evidence on how integration of Caring Science across administrative, operational, and clinical areas appears to contribute to meaningful patient quality and health outcomes. PMID- 26828077 TI - A Guideline to Fit Them All. PMID- 26828078 TI - Reply: To PMID 24852946. PMID- 26828079 TI - In Memorium, Professor Lester Mitscher. PMID- 26828080 TI - Author's Reply. PMID- 26828081 TI - Author's Reply. PMID- 26828082 TI - Art as an Expression of the Human Condition. PMID- 26828083 TI - [Roux-en-Y gastric bypass in a candidate for kidney transplant]. AB - Obesity is a factor limiting access to kidney transplantation because of the high risk of perioperative complications, worse graft function and patients' survival. We present a case of an obese patient (BMI-38 kg/m2) with hypertension, diabetes and end-stage kidney disease caused by chronic glomerulonephritis treated with hemodialysis, who was excluded from transplantation because of obesity. The patient underwent Roux-en-Y gastric by-pass surgery as a preparation for kidney transplantation. PMID- 26828084 TI - Which was the First Textbook of Anesthesia? PMID- 26828085 TI - Medicine-A Sweeping History: Teaching It or Trashing It? PMID- 26828086 TI - Mafutsuto-Ron: The First Anesthesia Textbook in the World. Bibliographic Review and English Translation. AB - On October 13, 1804, Seishu Hanaoka performed a mastectomy on Kan Aiya in Hirayama, Kii Province Japan, in what is considered to be the first operation under general anesthesia. She was anesthetized with a mixture of herbs known as Mafutsuto. Although Seishu did not record his anesthetic practices, his student, Gendai Kamada, documented the use of Mafutsuto in Mafutsuto-Ron. Written in 1839, Mafutsuto-Ron is 10 pages and covers six topics, including preoperative management, dosing and administering Mafutsuto, induction of general anesthesia, common errors, and postoperative precautions. Mafutsuto-Ron, therefore, meets the requirements to be considered the first extant anesthesia textbook. We present a complete English translation of Mafutsuto-Ron. PMID- 26828087 TI - History of Medicine in US Medical School Curricula. AB - STUDY OBJECTIVE: To determine the extent to which the history of medicine (HOM) and its related topics are included within the curriculum of accredited medical schools in the United States. DESIGN: Survey instrument. SETTING: US allopathic medical schools. MEASUREMENTS: An online survey was sent to officials from every medical school in the US. Respondents were asked to provide institutional identifiers, the presence of an HOM elective offered to medical students, the years during which the elective is offered, the existence of an HOM department, and the contact information for that particular department. Nonresponders were contacted by phone to elicit the same information. History of medicine electives included didactic sessions and seminars with varying degrees of credit offered in different years of medical school. MAIN RESULTS: Based on responses from 119 of 121 contacted medical schools (98%), 45 (37%) included formal lectures or weekly seminars in the medical school curriculum. Five (11%) curricula had or have required HOM, whereas 89% offered elective HOM instruction. Course duration and credit awarded varied. Eighteen (15%) medical schools included departments dedicated to HOM. Providing education in HOM was limited by faculty interest, clinical training hours, and low interest. CONCLUSIONS: Data collected by our study suggest that substantial barriers exist within the academic medical community towards a wider acceptance of the importance of HOM. Causes for such lack of interest include absence of questions on written or oral tests related to HOM, difficulty in publishing articles related to HOM in peer reviewed journals, near absence of research grants in HOM, difficulty in getting academic promotions or recognition for activities related to HOM, and a lack of support from academic chairpersons for activities related to HOM. PMID- 26828088 TI - Accepting Pain Over Comfort: Resistance to the Use of Anesthesia in the Mid-19th Century. AB - News of the successful use of ether anesthesia on October 16, 1846, spread rapidly through the world. Considered one of the greatest medical discoveries, this triumph over man's cardinal symptom, the symptom most likely to persuade patients to seek medical attention, was praised by physicians and patients alike. Incredibly, this option was not accepted by all, and opposition to the use of anesthesia persisted among some sections of society decades after its introduction. We examine the social and medical factors underlying this resistance. At least seven major objections to the newly introduced anesthetic agents were raised by physicians and patients. Complications of anesthesia, including death, were reported in the press, and many avoided anesthesia to minimize the considerable risk associated with surgery. Modesty prevented female patients from seeking unconsciousness during surgery, where many men would be present. Biblical passages stating that women would bear children in pain were used to discourage them from seeking analgesia during labor. Some medical practitioners believed that pain was beneficial to satisfactory progression of labor and recovery from surgery. Others felt that patient advocacy and participation in decision making during surgery would be lost under the influence of anesthesia. Early recreational use of nitrous oxide and ether, commercialization with patenting of Letheon, and the fighting for credit for the discovery of anesthesia suggested unprofessional behavior and smacked of quackery. Lastly, in certain geographical areas, notably Philadelphia, physicians resisted this Boston-based medical advance, citing unprofessional behavior and profit seeking. Although it appears inconceivable that such a major medical advance would face opposition, a historical examination reveals several logical grounds for the initial societal and medical skepticism. PMID- 26828089 TI - The Experiments on Electrical Anesthesia in Italy in the Second Half of the Nineteenth Century. A Dispute Between a Fearless Surgeon Patriot and a Positivist Researcher. AB - Electric anesthesia is the anesthesia, usually general anesthesia, produced by the application of an electrical current. This fascinating issue of the anesthesia history was made possible thanks to the pioneering experiments on electrotherapy and electrophysiology performed by two researchers: the neurologist Guillaume Duchenne (1806-1875) and the biologist Stephane Leduc (1853 1939). The aim of this study is the review of the dispute between two Italian scientists on the effectiveness of electric anesthesia in the second half of the 19th century. One of the two contenders was Rodolfo Rodolfi (1827-1896), an Italian surgeon and patriot who took part in the First Italian War of Independence of 1848, whereas the other protagonist of the dispute was the positivist Plinio Schivardi (1833-1908), a pupil of Duchenne who brought to Italy his knowledge of electrotherapy, collecting these experiences in the Theoretical Practical Manual of Electrotherapy, the first book on the subject written in Italian. PMID- 26828090 TI - End of Life Care during the Holidays? PMID- 26828091 TI - An Avuncular Stereotype Advertises Dr. George Hill's Laughing Gas. PMID- 26828092 TI - Ethereal Kindnesses. PMID- 26828093 TI - Clinical features and antenatal risk factors for postpartum-onset hypertensive disorders. AB - OBJECTIVE: To identify the clinical features and risk factors for diagnosis of a postpartum-onset hypertensive disorder. METHODS: A retrospective cohort study of singleton pregnancies. Clinical features of postpartum-onset hypertensive disorders were evaluated, and prenatal risk factors were also identified with a multivariate logistic regression model. RESULTS: Of 1,964 women, 57 (2.9%) developed hypertensive disorder after delivery. The independent risk factors were assisted reproductive technology, pre-pregnancy body mass index, chronic nephritis, hypothyroidism, high-normal blood pressure before or at delivery, and cesarean section. CONCLUSION: Careful monitoring of blood pressure should be considered for women with the identified risk factors even after delivery. PMID- 26828095 TI - Prognostic factors and survival study in high-grade glioma in the elderly. AB - Background Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumour in adults. Due to the ageing of the population, diagnosis in the elderly is becoming more common. The aim of this study was to analyse different combinations of treatments and to identify preoperative factors, including O6 methylguanine-DNA methyltransferase status, that may be associated with decreased survival among patients older than 70 years. Methods and materials We retrospectively included all patients over 70 years of age, who underwent surgery at the Department of Neurosurgery (HUCA and HUMV) and were diagnosed of GBM by pathological criteria from January 2007 to September 2014. Results Eighty-one patients were analysed, whose mean age was 75 (SD 4) and 48 were male. Karnofsky performance status (KPS) was over 70 in 61 patients and 38.3% presented with motor deficit. Sixty-three patients underwent resection, and 18 had only a diagnostic biopsy. The complication rate was 17.28% and mortality rate was 7.4%. Survival was increased in patients who received radiotherapy (n = 41) or additional chemotherapy (n = 26) (p < 0.001). KPS < 70 was an independent factor associated with low-rate survival. Patients with optimal treatment had a median survival of 8 months compared to patients with suboptimal treatment who had a median survival of 4 months (p < 0.001). Conclusions This study suggests that KPS is the most important preoperative prognostic factor. Maximal safe resection followed by radical radiotherapy and temozolomide might be the optimal treatment of choice since glioblastoma-diagnosed patients over 70 years of age showed a statistically significant survival benefit. PMID- 26828094 TI - Prevalence of qacA/B Genes and Mupirocin Resistance Among Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates in the Setting of Chlorhexidine Bathing Without Mupirocin. AB - OBJECTIVE: We aimed to determine the frequency of qacA/B chlorhexidine tolerance genes and high-level mupirocin resistance among MRSA isolates before and after the introduction of a chlorhexidine (CHG) daily bathing intervention in a surgical intensive care unit (SICU). DESIGN: Retrospective cohort study (2005 2012) SETTING: A large tertiary-care center PATIENTS: Patients admitted to SICU who had MRSA surveillance cultures of the anterior nares METHODS: A random sample of banked MRSA anterior nares isolates recovered during (2005) and after (2006 2012) implementation of a daily CHG bathing protocol was examined for qacA/B genes and high-level mupirocin resistance. Staphylococcal cassette chromosome mec (SCCmec) typing was also performed. RESULTS: Of the 504 randomly selected isolates (63 per year), 36 (7.1%) were qacA/B positive (+) and 35 (6.9%) were mupirocin resistant. Of these, 184 (36.5%) isolates were SCCmec type IV. There was a significant trend for increasing qacA/B (P=.02; highest prevalence, 16.9% in 2009 and 2010) and SCCmec type IV (P<.001; highest prevalence, 52.4% in 2012) during the study period. qacA/B(+) MRSA isolates were more likely to be mupirocin resistant (9 of 36 [25%] qacA/B(+) vs 26 of 468 [5.6%] qacA/B(-); P=.003). CONCLUSIONS: A long-term, daily CHG bathing protocol was associated with a change in the frequency of qacA/B genes in MRSA isolates recovered from the anterior nares over an 8-year period. This change in the frequency of qacA/B genes is most likely due to patients in those years being exposed in prior admissions. Future studies need to further evaluate the implications of universal CHG daily bathing on MRSA qacA/B genes among hospitalized patients. PMID- 26828097 TI - Ecology And The Science Of Psychology. PMID- 26828096 TI - The Transmembrane Domain of HIV-1 gp41 Inhibits T-Cell Activation by Targeting Multiple T-Cell Receptor Complex Components through Its GxxxG Motif. AB - To successfully infect and persist within its host, HIV-1 utilizes several immunosuppressive motifs within its gp41 envelope glycoprotein to manipulate and evade the immune system. The transmembrane domain (TMD) of gp41 downregulates T cell receptor (TCR) signaling through a hitherto unknown mechanism. Interactions between TMDs within the membrane milieu have been shown to be typically mediated by particular amino acids, such as interactions between basic and acidic residues and dimerization motifs as GxxxG. The HIV-1 TMD exhibits both a polar arginine (Arg(696)) residue and a GxxxG motif, making them ideal candidates for mediators of TMD-TCR interaction. Using a primary T-cell activation assay and biochemical and biophysical methods, we demonstrate that the gp41 TMD directly interacts with TMDs of the TCR and the CD3 coreceptors (delta, gamma, and epsilon) within the membrane, presumably leading to impairment of complex assembly. Additionally, we reveal that although Arg(696) does not affect TMD immunosuppression, the GxxxG motif is crucial in mediating gp41's TMD interaction with the CD3 coreceptors of the TCR. These findings suggest that compared with other gp41 immunosuppressive motifs, the gp41 TMD has multiple targets within the TCR complex, suggesting less susceptibility to evolutionary pressure and consequently being advantageous for the virus over the host immune response. Furthermore, as the GxxxG motif mediates interactions of the gp41 TMD with multiple receptors, it emerges as an attractive drug target. This multitarget inhibitory mechanism might be a strategy utilized by HIV to interfere with the function of additional host receptors. PMID- 26828098 TI - Group And Individual Regularities In Trait Inference: A Multidimensional Scaling Analysis. AB - This study concerned regularities in trait inference, the manner in which limited information about another person is used to form a consistent total impression. An individual differences model for multidimensional scaling was appraised as a method for faithfully strong both broad culturally- determined standards, and differently-structured points of view. Judgments of likelihood of joint occurrence of trait pairs and measures of cognition were obtained from 139 subjects. Scaling analyses resulted in two points of view, the largest of which yielded dimensions of interpersonal affectivity, harmfulness, and charitableness. S e w a t e analyses of randomly divided groups yielded indices of dimension stability ranging up to .99. The results support the view that the multidimensional scaling model can serve well to explain and order trait inference data. PMID- 26828099 TI - Personality Consistencies In Judgment : Dimensions Of Role Constructs. AB - Eighty-four males and 79 females judged similarities and differences among 16 dominant figures important in interpersonal functioning, such as mother, self, best friend, or liked -her. The individual differences model of multidimensional sealing, in separate analyses far the two sexes, uncovered six dimensions of viewpoint for females and seven for males. Individual scores on these viewpoint dimensions were found to be significantly correlated with certain cognitive and personality measures. Separate multidimensional scaling spaces were obtained for each viewpoint dimension, and a selected set of these structures were compared and their personality correlates exemplified. PMID- 26828100 TI - The Effect Of Group Psychotherapy On Interpersonal Perceptions Of Psychiatric Patients. AB - Matched groups of psychiatric patients were randomly assigned either to small group psychotherapy or to a control condition. The Revised Inter- personal Check List was administered three times (zero, three, and six weeks from the time therapy began) with five instructional sets (I am, Most People are, etc.). The results were first factor analyzed by item in accordance with a model developed by Horst (1963), then factor scores were computed, and finally the effects of experimental treatments (group, occasion, set) on the factor scores were evaluated by analysis of variance. Two of eighteen group-by-occasion interactions were significant (p < .01) and suggested that group therapy influenced the interpersonal perceptions of participants in the direction of seeing themselves and others as less assertive and pompous, Seven of eighteen main effects of instructional set were significant (p < .01) and suggested that patients tend to see themselves as unassertive and indulgent of others. It was concluded that Horst's new factor analytic approach to assessing change was promising, particularly in view of the failure of previous efforts to yield significant findings. PMID- 26828101 TI - The Equivalence Of Psychotic Syndromes Across Two Media. AB - The study goal was to test the equivalence of ten dimensions of psychotic behavior across two measuring media. The data consisted of ratings of 814 newly admitted schizophrenics made in the interview and on the ward. The factored. A least squares solution of a hypothesis matrix yielded ten clear factors of which eight were defined both by ward and interview measures. PMID- 26828102 TI - The Dimensionality Of The CPI Socialization Scale And An Empirically Derived Typology Among Delinquent And Nondelinquent Boys. AB - The 64 items of the CPI So scale were cluster analyzed in a sample of 318 males into 3 main dimensions: C-1-Stable home and school adjustment versus waywardness and dissatisfaction with family; C-2-Optimism and trust in others versus dysphoria, distrust and alienation; C-3-Observation of convention versus asocial role and attitude. The initial sample was comprised of 84 school disciplinary problems (DP), 75 institutionalized delinquents (D), and 169 nondelinquent (ND) boys. A cross-validational sample included 121 ND versus 121 D boys. Each of the 3 clusters differen- tiated significantly between D and ND subsamples. From an inverse cluster analysis of the initial 318 boys over the 3 cluster dimensions, 11 types were generated. Four of these were diagnostic of delinquency, 6 of nondelinquency, and 1 pertained primarily to the intermediate criterion group of school disciplinary problems. PMID- 26828103 TI - Optimal Stimulus Parameters In Avoidance Conditioning Of Inbred Strains Of Mice. AB - Highly inbred mice of fast and slow conditioning strains (N = 228) were trained in avoidance conditioning and 180 were continued to extinction. The principal goal was to determine optimal stimulus conditions for fast learning, small variances, and maximal strain differences. Conclusions are: a) the major effect of change in CS-US and intertrial intervals occurs, respectively, for intervals less than 3 sec. and 60 sec.; b) change in amperage (150-400 pa) or voltage (250 400 v.) caused no significant differences; c) strain differences in extinction occurred after nearly optimal conditioning, and d) strain differences were altered considerably as stimulus conditions became optimal. Optimal levels of parameters are: 3 sec. CS-US interval, 120-sec. intertrial interval, and 400 v. (220 K ohm impedance circuit). PMID- 26828104 TI - Isolating Change And Invariance In Patterns Of Behavior. AB - General approaches which may be taken in the study of change and in- variance in patterns of behavior are presented and compared. These are classified according to whether data are gathered by "ideal" means, in which the same entities are assessed with the same measuring devices on several occasions, or data are gathered by "less-than-ideal" means, in which change of occasion is confounded with change in the sample of entities or is confounded with change in the sample of measuring devices. Several estimation and hypothesis-testing procedures are presented as appropriate for use with data gathered in one or the other of these ways. These include Tucker's multi-mode factoring technique, his inter-battery factoring procedure, Meredith's methods for rotating to achieve factorial invariance and various techniques of use in evaluating the significance of difference of vectors and matrices. Newly developed least-squares techniques, based in part upon discriminant function principles, are presented in some detail. The various study-design and statistical-method possibilities are evaluated for the amount and kind of information they could provide about stable and dynamic patterns of behavior. PMID- 26828105 TI - Unrestricted Cluster And Factor Analysis, With Applications To The MMPI And Holzinger-Harman Problems. AB - A solution is provided for the problem of large numbers of variables in V analysis and of large numbers of subjects in 0-analysis. The solution is that of estimating the Structure in the total set from the structures found in manageable samples of the total set. The samples are drawn randomly; structures of each are computed by existing BC TRY programs; finally the structures of the random samples are combined using new BC TRY programs. Examples of the complete analyses in two separate studies are given. PMID- 26828106 TI - The Scree Test For The Number Of Factors. PMID- 26828107 TI - Triarchic Psychopathy Measure: Validity in Relation to Normal-Range Traits, Personality Pathology, and Psychological Adjustment. AB - The triarchic model of psychopathy replaces a syndromal view of this pathological personality condition with a tripartite trait-based conception, positing three distinct phenotypic dispositions as building blocks for what theorists have traditionally termed psychopathy. The Triarchic Psychopathy Measure (TriPM) offers an efficient means for measuring the three dimensions to facilitate research on the model's validity. We tested the reliability of the TriPM as well as its convergent and discriminant validity with respect to differing models of personality and other criterion variables reflecting social-emotional adjustment and mental health in an undergraduate participant sample (n = 120). The TriPM evidenced excellent internal consistencies, good test-retest reliability, and strong validity consistent with the triarchic model. We discuss the results with respect to prior research and offer suggestions for future research on the validity of the TriPM and the triarchic model. PMID- 26828108 TI - A Head-to-Head Comparison of the Personality Inventory for DSM-5 (PID-5) With the Personality Diagnostic Questionnaire-4 (PDQ-4) in Predicting the General Level of Personality Pathology Among Community Dwelling Subjects. AB - In order to evaluate if measures of DSM-5 Alternative PD Model domains predicted interview-based scores of general personality pathology when compared to self report measures of DSM-IV Axis II/DSM-5 Section II PD criteria, 300 Italian community adults were administered the Iowa Personality Disorder Screen (IPDS) interview, the Personality Inventory for DSM-5 (PID-5), and the Personality Diagnostic Questionnaire-4+ (PDQ-4+). Multiple regression analyses showed that the five PID-5 domain scales collectively explained an adequate rate of the variance of the IPDS interview total score. This result was slightly lower than the amount of variance in the IPDS total score explained by the 10 PDQ-4+ scales. The PID-5 traits scales performed better than the PDQ-4+, although the difference was marginal. Hierarchical regression analyses revealed that the PID-5 domain and trait scales provided a moderate, but significant increase in the prediction of the general level of personality pathology above and beyond the PDQ-4+ scales. PMID- 26828109 TI - Probing the Role of Ceramide Headgroup Polarity in Short-Chain Model Skin Barrier Lipid Mixtures by 2H Solid-State NMR Spectroscopy. AB - The thermoptropic phase behaviors of two stratum corneum model lipid mixtures composed of equimolar contributions of either Cer[NS18] or Cer[NP18] with stearic acid and cholesterol were compared. Each component of the mixture was specifically deuterated such that the temperature-dependent (2)H NMR spectra allowed disentanglement of the complicated phase polymorphism of these lipid mixtures. While Cer[NS] is based on the sphingosine backbone, Cer[NP] features a phytosphingosine, which introduces an additional hydroxyl group into the headgroup of the ceramide and abolishes the double bond. From the NMR spectra, the individual contributions of all lipids to the respective phases could be determined. The comparison of the two lipid mixtures reveals that Cer[NP] containing mixtures have a tendency to form more fluid phases. It is concluded that the additional hydroxyl group of the phytosphingosine-containing ceramide Cer[NP18] in mixture with chain-matched stearic acid and cholesterol creates a packing defect that destabilizes the orthorhombic phase state of canonical SC mixtures. This steric clash favors the gel phase and promotes formation of fluid phases of Cer[NP] containing lipid mixtures at lower temperature compared to those containing Cer[NS18]. PMID- 26828111 TI - Genetic polymorphisms of human UDP-glucuronosyltransferase (UGT) genes and cancer risk. AB - Identification of genetic polymorphisms that contribute to the risk of developing cancers is important for cancer prevention. The most recent human genome GRCh38/hg38 assembly (2013) reveals thousands of genetic polymorphisms in human uridine diphosphoglucuronosyltransferase (UGT) genes. Among these, a large number of polymorphisms at the UGT1A and UGT2B genes have been shown to modulate UGT gene promoter activity or enzymatic activity. Glucuronidation plays an important role in the metabolism and clearance of endogenous and exogenous carcinogenic compounds, and this reaction is primarily catalyzed by the UGT1A and UGT2B enzymes. Therefore, it has long been hypothesized that UGT polymorphisms that reduce the capacity to glucuronidate carcinogens and other types of cancer promoting molecules (e.g. sex hormones) are associated with an increased risk of developing cancers. A large number of case-control studies have investigated this hypothesis and these studies identified numerous UGT polymorphisms in UGT1A and UGT2B genes as genetic risk factors for a wide variety of cancers, including bladder, breast, colorectal, endometrial, esophageal, head and neck, liver, lung, prostate, and thyroid. These UGT polymorphisms may be cancer causative polymorphisms, or be linked to as yet undefined causative polymorphisms, either in UGT genes or neighboring genes. This article presents a comprehensive review of these case-control studies, discusses current areas of uncertainty, and highlights future research directions in this field. PMID- 26828110 TI - Spatially coordinated dynamic gene transcription in living pituitary tissue. AB - Transcription at individual genes in single cells is often pulsatile and stochastic. A key question emerges regarding how this behaviour contributes to tissue phenotype, but it has been a challenge to quantitatively analyse this in living cells over time, as opposed to studying snap-shots of gene expression state. We have used imaging of reporter gene expression to track transcription in living pituitary tissue. We integrated live-cell imaging data with statistical modelling for quantitative real-time estimation of the timing of switching between transcriptional states across a whole tissue. Multiple levels of transcription rate were identified, indicating that gene expression is not a simple binary 'on-off' process. Immature tissue displayed shorter durations of high-expressing states than the adult. In adult pituitary tissue, direct cell contacts involving gap junctions allowed local spatial coordination of prolactin gene expression. Our findings identify how heterogeneous transcriptional dynamics of single cells may contribute to overall tissue behaviour. PMID- 26828112 TI - Supramolecular structure of enterobacterial wild-type lipopolysaccharides (LPS), fractions thereof, and their neutralization by Pep19-2.5. AB - Lipopolysaccharides (LPS) belong to the strongest immune-modulating compounds known in nature, and are often described as pathogen-associated molecular patterns (PAMPs). In particular, at higher concentrations they are responsible for sepsis and the septic shock syndrome associated with high lethality. Since most data are indicative that LPS aggregates are the bioactive units, their supramolecular structures are considered to be of outmost relevance for deciphering the molecular mechanisms of its bioactivity. So far, however, most of the data available addressing this issue, were published only for the lipid part (lipid A) and the core-oligosaccharide containing rough LPS, representing the bioactive unit. By contrast, it is well known that most of the LPS specimen identified in natural habitats contain the smooth-form (S-form) LPS, which carry additionally a high-molecular polysaccharide (O-chain). To fill this lacuna and going into a more natural system, here various wild-type (smooth form) LPS including also some LPS fractions were investigated by small-angle X-ray scattering with synchrotron radiation to analyze their aggregate structure. Furthermore, the influence of a recently designed synthetic anti-LPS peptide (SALP) Pep19-2.5 on the aggregate structure, on the binding thermodynamics, and on the cytokine-inducing activity of LPS were characterized, showing defined aggregate changes, high affinity binding and inhibition of cytokine secretion. The data obtained are suitable to refine our view on the preferences of LPS for non-lamellar structures, representing the highest bioactive forms which can be significantly influenced by the binding with neutralizing peptides such as Pep19 2.5. PMID- 26828113 TI - Biomineralization pathways in a foraminifer revealed using a novel correlative cryo-fluorescence-SEM-EDS technique. AB - Foraminifera are marine protozoans that are widespread in oceans throughout the world. Understanding biomineralization pathways in foraminifera is particularly important because their calcitic shells are major components of global calcium carbonate production. We introduce here a novel correlative approach combining cryo-SEM, cryo-fluorescence imaging and cryo-EDS. This approach is applied to the study of ion transport processes in the benthic foraminifer genus Amphistegina. We confirm the presence of large sea water vacuoles previously identified in intact and partially decalcified Amphistegina lobifera specimens. We observed relatively small vesicles that were labelled strongly with calcein, and also identified magnesium (Mg)-rich mineral particles in the cytoplasm, as well as in the large sea water vacuoles. The combination of cryo-microscopy with elemental microanalysis and fluorescence imaging reveals new aspects of the biomineralization pathway in foraminifera which are, to date, unique in the world of biomineralization. This approach is equally applicable to the study of biomineralization pathways in other organisms. PMID- 26828114 TI - Pathology in the Medical Profession?: Taking the Pulse of Physician Wellness and Burnout. AB - CONTEXT: -In the past decades, physician wellness has diminished in every aspect of professional life. Burnout symptoms in the United States affect 30% to 68% of physicians overall-exceeding the levels of any other professional group. The ramifications of burnout present an underrecognized crisis in the health care system that carries the consequences of personal, professional, institutional, and societal costs. OBJECTIVE: -To bring to light the elements of current medical practice that contribute to physician professional fulfillment and burnout. Intervention measures, steps toward burnout prevention, and the present limitations thereof are also addressed. DATA SOURCES: -This narrative literature review was performed by using studies in PubMed (National Center for Biotechnology Information) and large online physician surveys, published through December 2015. Because of geographic differences, the review is primarily concentrated on physicians across specialties in the United States. Small studies and those of single disciplines were excluded. CONCLUSIONS: -Many physicians learn to tolerate burnout symptoms despite negative personal consequences. Long term work-related stress, however, may lead to the potential for negative effects on the quality of patient care, and to attrition. Interestingly, the factors that enhance physician fulfillment and those that may precipitate burnout symptoms are distinct. Optimization of physician well-being, therefore, requires tailored approaches in each of these 2 dimensions and is most likely to succeed if it includes approaches that are customized to career phase, physician specialty, and practice setting. Importantly, organization leaders must prioritize this issue and provide sustained support for wellness initiatives, to foster a culture that is conducive to physician well-being. PMID- 26828115 TI - Synthesis of alpha-Aminonaphthalenes via Copper-Catalyzed Aminobenzannulation of (o-Alkynyl)arylketones with Amines. AB - A copper-catalyzed aminobenzannulation of (o-alkynyl)arylketones with amines has been developed. This method features the use of a cheap copper catalyst, the facile annulation involving various amines, and the good functional group tolerance. PMID- 26828116 TI - Pyridyl Directed Catalyst-Free trans-Hydroboration of Internal Alkynes. AB - We report the first examples of straightforward trans-hydroboration of internal alkynes at room temperature with 9-BBN, producing five-membered BN-heterocycles. Contrary to conventional cis-hydroboration, we demonstrate that the introduction of a pyridyl group switches the stereoselectivity of the reaction. A hydride migration mechanism has been proposed and supported by DFT calculations for the trans-hydroboration. This new hydroboration approach allows facile construction of new blue fluorescent BN-heterocyclic compounds. PMID- 26828117 TI - Cloning, expression, and purification of Chlamydomonas reinhardtii CC-503 sedoheptulose 1,7-bisphosphatase in Escherichia coli. AB - Sedoheptulose 1,7-bisphosphatase (SBPase), a nuclear-encoded chloroplastic enzyme, is an important rate-limiting enzyme of the carbon fixation cycle (Calvin cycle). SBPase is unique to only photosynthetic organisms and is involved in the regeneration of ribulose-1,5-bisphosphate. SBPases from several sources have been studied for their induction and regulation. However, SBPase from Chlamydomonas reinhardtii CC-503, the widely studied model microalga, has not been isolated and functionally confirmed to date. In this study, the full-length cDNA for SBPase was isolated from C. reinhardtii CC-503 using anchored oligo(dT)24VGN primer for reverse transcription. The SBPase cDNA was cloned into pET28a expression vector for the production of 6X His-tagged protein in Escherichia coli BL21 (DE3) strain. Although initially most of the enzyme was obtained as insoluble protein aggregates, solubilization of protein was improved by optimization of protein induction with respect to growth temperature and isopropyl beta-D-1 thiogalactopyranoside concentrations. The induced protein was purified by immobilized metal affinity chromatography using nickel-nitrilotriacetic acid resin in a phosphate-free buffer leading to an accurate SBPase activity measurement. The present study demonstrates, for the first time, successful cloning of C. reinhardtii CC-503 SBPase in E. coli leading to the expression of a functionally active enzyme. PMID- 26828118 TI - Arsenic(V) Incorporation in Vivianite during Microbial Reduction of Arsenic(V) Bearing Biogenic Fe(III) (Oxyhydr)oxides. AB - The dissolution of arsenic-bearing iron(III) (oxyhydr)oxides during combined microbial iron(III) and arsenate(V) reduction is thought to be the main mechanism responsible for arsenic mobilization in reducing environments. Besides its mobilization during bioreduction, arsenic is often resequestered by newly forming secondary iron(II)-bearing mineral phases. In phosphate-bearing environments, iron(II) inputs generally lead to vivianite precipitation. In fact, in a previous study we observed that during bioreduction of arsenate(V)-bearing biogenic iron(III) (oxyhydr)oxides in phosphate-containing growth media, arsenate(V) was immobilized by the newly forming secondary iron(II) and iron(II)/iron(III)mineral phases, including vivianite. In the present study, changes in arsenic redox state and binding environment in these experiments were analyzed. We found that arsenate(V) partly replaced phosphate in vivianite, thus forming a vivianite symplesite solid solution identified as Fe3(PO4)1.7(AsO4)0.3.8H2O. Our data suggests that in order to predict the fate of arsenic during the bioreduction of abiogenic and biogenic iron(III) (oxyhydr)oxides in arsenic-contaminated environments, the formation of symplesite-vivianite minerals needs to be considered. Indeed, such mineral phases could contribute to a delayed and slow release of arsenic in phosphate-bearing surface and groundwater environments. PMID- 26828119 TI - Tribological Behavior of Aqueous Copolymer Lubricant in Mixed Lubrication Regime. AB - Although a number of experiments have been attempted to investigate the lubrication of aqueous copolymer lubricant, which is applied widely in metalworking operations, a comprehensive theoretical investigation at atomistic level is still lacking. This study addresses the influence of loading pressure and copolymer concentration on the structural properties and tribological performance of aqueous copolymer solution of poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) (PPO-PEO-PPO) at mixed lubrication using a molecular dynamic (MD) simulation. An effective interfacial potential, which has been derived from density functional theory (DFT) calculations, was employed for the interactions between the fluid's molecules and iron surface. The simulation results have indicated that the triblock copolymer is physisorption on iron surface. Under confinement by iron surfaces, the copolymer molecules form lamellar structure in aqueous solution and behave differently from its bulk state. The lubrication performance of aqueous copolymer lubricant increases with concentration, but the friction reduction is insignificant at high loading pressure. Additionally, the plastic deformation of asperity is dependent on both copolymer concentration and loading pressure, and the wear behavior shows a linear dependence of friction force on the number of transferred atoms between contacting asperities. PMID- 26828120 TI - Inward multivesiculation at the basal membrane of adherent giant phospholipid vesicles. AB - Adherent giant vesicles composed of phosphatidylcholine, phosphatidylserine and biotinylated lipids form clusters of inward spherical buds at their basal membrane. The process is spontaneous and occurs when the vesicles undergo a sequence of osmotic swelling and deswelling. The daughter vesicles have a uniform size (diameter ~ 2-3 MUm), engulf small volumes of outer fluid and remain attached to the region of the membrane from which they generate, even after restoring the isotonicity. A pinning-sealing mechanism of long-wavelength modes of membrane fluctuations is proposed, by which the just-deflated vesicles reduce the surplus of membrane area and avoid excessive spreading and compression via biotin anchors. The work discusses the rationale behind the mechanism that furnishes GUVs with basal endovesicles, and its prospective use to simulate cellular events or to create molecular carriers. PMID- 26828121 TI - Solvent-exposed lipid tail protrusions depend on lipid membrane composition and curvature. AB - The stochastic protrusion of hydrophobic lipid tails into solution, a subclass of hydrophobic membrane defects, has recently been shown to be a critical step in a number of biological processes like membrane fusion. Understanding the factors that govern the appearance of lipid tail protrusions is critical for identifying membrane features that affect the rate of fusion or other processes that depend on contact with solvent-exposed lipid tails. In this work, we utilize atomistic molecular dynamics simulations to characterize the likelihood of tail protrusions in phosphotidylcholine lipid bilayers of varying composition, curvature, and hydration. We distinguish two protrusion modes corresponding to atoms near the end of the lipid tail or near the glycerol group. Through potential of mean force calculations, we demonstrate that the thermodynamic cost for inducing a protrusion depends on tail saturation but is insensitive to other bilayer structural properties or hydration above a threshold value. Similarly, highly curved vesicles or micelles increase both the overall frequency of lipid tail protrusions as well as the preference for splay protrusions, both of which play an important role in driving membrane fusion. In multi-component bilayers, however, the incidence of protrusion events does not clearly depend on the mismatch between tail length or tail saturation of the constituent lipids. Together, these results provide significant physical insight into how system components might affect the appearance of protrusions in biological membranes, and help explain the roles of composition or curvature-modifying proteins in membrane fusion. PMID- 26828123 TI - High Catalytic Activity and Chemoselectivity of Sub-nanometric Pd Clusters on Porous Nanorods of CeO2 for Hydrogenation of Nitroarenes. AB - Sub-nanometric Pd clusters on porous nanorods of CeO2 (PN-CeO2) with a high Pd dispersion of 73.6% exhibit the highest catalytic activity and best chemoselectivity for hydrogenation of nitroarenes to date. For hydrogenation of 4 nitrophenol, the catalysts yield a TOF of ~44059 h(-1) and a chemoselectivity to 4-aminophenol of >99.9%. The superior catalytic performance can be attributed to a cooperative effect between the highly dispersed sub-nanometric Pd clusters for hydrogen activation and unique surface sites of PN-CeO2 with a high concentration of oxygen vacancy for an energetically and geometrically preferential adsorption of nitroarenes via nitro group. The high concentration of surface defects of PN CeO2 and large Pd dispersion contribute to the enhanced catalytic activity for the hydrogenation reactions. The high chemoselectivity is mainly governed by the high Pd dispersion on the support. The catalysts also deliver high catalytic activity and selectivity for nitroaromatics with various reducible substituents into the corresponding aminoarenes. PMID- 26828122 TI - The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. AB - The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. The hTPPT is highly expressed in the colon, but not in other regions of the intestinal tract and is localized exclusively at the apical membrane domain of epithelia. The hTPPT protein is predicted to have multiple TM domains with a number of putative N-glycosylation sites, but it is not known if the protein is actually glycosylated, and if so at which site, and their role in the functionality of the transporter. Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. Glycosylation of hTPPT was shown, by mean of site-directed mutagenesis, to occur at Asn(69), Asn(155), Asn(197), Asn(393), and Asn(416). However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). Results of this study showed, for the first time, that the hTPPT is glycosylated and that N-linked glycosylation occurs at multiple sites with some of them being important for function. The results also provide an indirect support for a membrane topology for hTPPT with 10 transmembrane domains as predicted by the TMHMM transmembrane helixes prediction program. PMID- 26828124 TI - Evaluation of Aqueous Flare Levels Following Intravitreal Ranibizumab Injection for Neovascular Age-related Macular Degeneration. AB - PURPOSE: To evaluate aqueous flare levels following intravitreal ranibizumab injection for neovascular age-related macular degeneration (AMD). METHODS: In total, 81 eyes of 79 patients who underwent intravitreal ranibizumab injection for neovascular AMD were included. Aqueous flare was evaluated before pupillary dilatation with Kowa FM-600 laser flare meter at baseline, and 1 day, and 1 month after intravitreal administration of ranibizumab 0.5 mg (0.05 mL). RESULTS: The mean anterior chamber flare was 10.7 +/- 6.8 (range: 1.5-35.4) ph/ms before the injection, 12.5 +/- 8.9 (range: 0.3-43) ph/ms on the first day, and 9.9 +/- 5.7 (range: 0.2-28.4) ph/ms in the first month. On the first day, a subtle increasing of flare was observed. However, the difference between the mean aqueous flare levels at baseline and postoperative first day and first month was not statistically different (p>0.05). CONCLUSIONS: No significant short-term intraocular inflammation was noted in these eyes receiving ranibizumab for the treatment of neovascular AMD. PMID- 26828125 TI - Health insurance in India: what do we know and why is ethnographic research needed. AB - The percentage of India's national budget allocated to the health sector remains one of the lowest in the world, and healthcare expenditures are largely out-of pocket (OOP). Currently, efforts are being made to expand health insurance coverage as one means of addressing health disparity and reducing catastrophic health costs. In this review, we document reasons for rising interest in health insurance and summarize the country's history of insurance projects to date. We note that most of these projects focus on in-patient hospital costs, not the larger burden of out-patient costs. We briefly highlight some of the more popular forms that government, private, and community-based insurance schemes have taken and the results of quantitative research conducted to assess their reach and cost effectiveness. We argue that ethnographic case studies could add much to existing health service and policy research, and provide a better understanding of the life cycle and impact of insurance programs on both insurance holders and healthcare providers. Drawing on preliminary fieldwork in South India and recognizing the need for a broad-based implementation science perspective (studying up, down and sideways), we identify six key topics demanding more in depth research, among others: (1) public awareness and understanding of insurance; (2) misunderstanding of insurance and how this influences health care utilization; (3) differences in behavior patterns in cash and cashless insurance systems; (4) impact of insurance on quality of care and doctor-patient relations; (5) (mis)trust in health insurance schemes; and (6) health insurance coverage of chronic illnesses, rehabilitation and OOP expenses. PMID- 26828126 TI - A new cembrane-type diterpenoid from Bornean liverwort Chandonanthus hirtellus. AB - A new compound, chandonanol (1), along with four known compounds, chandonanthone (2), iso-chandonanthone (3), anastreptene (4), and (6R,7S)-sesquiphellandrene (5), was isolated from the MeOH extract of Bornean liverwort Chandonanthus hirtellus. The structure of the new metabolite was established by analyses of the spectroscopic data (1D NMR, 2D NMR, HRESIMS, and IR). These compounds were tested for their activity against antibiotic-resistant clinical strains. Chandonanol (1) exhibited potent bactericidal activity against Staphylococcus aureus and Escherichia coli. PMID- 26828129 TI - The Lived Experience of the Adolescent Sex Offender: A Phenomenological Case Study. AB - Treatment for adolescents with sexually maladaptive behaviors is a continuing intervention that is changing and developing as greater understanding about this population of adolescents is obtained. The majority of treatment programs for adolescent sexually maladaptive behavior contain programming components that include cognitive distortions/thinking errors. Interviews including a conceptual mapping exercise were conducted with four adolescents adjudicated to a secure care program for sexual behaviors. All four boys completed an interview and a conceptual map of their perceived experiences as an adolescent with sexual maladaptive behaviors. All interviews were audio recorded. Analysis of the interviews and conceptual mappings yielded five themes present in the boys' experience as well as a consideration of the role early trauma may have in the establishment of cognitive distortion development. Contributing environmental and familial factors also play an important part in sustaining cognitive distortion. Main themes include: loss of responsible father or father figure, inability to regulate emotion, lack of personal and parental boundaries, and early exposure to pornography. The contributing influence of responsible male father figures may play an even greater role in the lives of young males than originally thought. How the adolescent inaccurately perceives his environment--in essence what he tells himself and continues to tell himself to make sense of his world--are building blocks in the development and continuation of thinking errors/cognitive distortions used to commit and justify sexual offending behaviors. PMID- 26828128 TI - Achieving Extreme Utilization of Excitons by an Efficient Sandwich-Type Emissive Layer Architecture for Reduced Efficiency Roll-Off and Improved Operational Stability in Organic Light-Emitting Diodes. AB - It has been demonstrated that the efficiency roll-off is generally caused by the accumulation of excitons or charge carriers, which is intimately related to the emissive layer (EML) architecture in organic light-emitting diodes (OLEDs). In this article, an efficient sandwich-type EML structure with a mixed-host EML sandwiched between two single-host EMLs was designed to eliminate this accumulation, thus simultaneously achieving high efficiency, low efficiency roll off and good operational stability in the resulting OLEDs. The devices show excellent electroluminescence performances, realizing a maximum external quantum efficiency (EQE) of 24.6% with a maximum power efficiency of 105.6 lm W(-1) and a maximum current efficiency of 93.5 cd A(-1). At the high brightness of 5,000 cd m(-2), they still remain as high as 23.3%, 71.1 lm W(-1), and 88.3 cd A(-1), respectively. And, the device lifetime is up to 2000 h at initial luminance of 1000 cd m(-2), which is significantly higher than that of compared devices with conventional EML structures. The improvement mechanism is systematically studied by the dependence of the exciton distribution in EML and the exciton quenching processes. It can be seen that the utilization of the efficient sandwich-type EML broadens the recombination zone width, thus greatly reducing the exciton quenching and increasing the probability of the exciton recombination. It is believed that the design concept provides a new avenue for us to achieve high performance OLEDs. PMID- 26828127 TI - Strontium attenuates rhBMP-2-induced osteogenic differentiation via formation of Sr-rhBMP-2 complex and suppression of Smad-dependent signaling pathway. AB - Strontium (Sr(2+)) has pronounced effects on stimulating bone formation and inhibiting bone resorption in bone regeneration. In this current study, the effect and the underlying mechanism involved of Sr(2+) on the biological activity of bone morphogenetic protein-2 (BMP-2) were studied in detail with pluripotent skeletal muscle myogenic progenitor C2C12 model cell line. The results indicated that Sr(2+) could bind recombinant human BMP-2 (rhBMP-2) rapidly, even in the presence of Ca(2+) and Mg(2+), and inhibited rhBMP-2-induced osteogenic differentiation in vitro and osteogenetic efficiency in vivo. Further studies demonstrated that Sr(2+) treatment undermined the binding capacity of rhBMP-2 with its receptor BMPRIA and thus attenuated Smad 1/5/8 phosphorylation without affecting their dephosphorylation in C2C12 cells. Furthermore, circular dichroism spectroscopy, fluorescence spectroscopy and X-ray photoelectron spectroscopy all revealed that the inhibitory effect of Sr(2+) on the rhBMP-2 osteogenic activity was associated with the formation of Sr-rhBMP-2 complex and ensuing enhancement of beta-sheet structure. Our work suggests the activity of rhBMP-2 to induce osteogenic differentiation was decreased by directly interaction with free Sr ions in solution, which should provide guide and assist for development of BMP-2 based materials for bone regeneration. STATEMENT OF SIGNIFICANCE: Due to easy denaturation and ensuing the reduced activity of rhBMP-2, preserving/enhancing the capacity of rhBMP-2 to induce osteogenic differentiation is of critical importance in developing the protein-based therapy. Cations as effective elements influence the conformation and thereby the bioactivity of protein. Strontium (Sr(2+)), stimulating bone formation and inhibiting bone resorption, has been incorporated into biomaterials/scaffold to improve the bioactivity for bone regeneration applications. However, Sr(2+)-induced changes in the conformation and bioactivity of BMP-2 have never been investigated. In this study, the formation of Sr-rhBMP-2 complex inhibited the osteogenic differentiation in vitro and osteogenetic efficiency in vivo through the inhibition of BMP/Smad signaling pathway, providing guidance for development of Sr-containing BMP-2-based bone scaffold/matrice and other Sr-dopped protein therapy. PMID- 26828130 TI - The short Working Alliance Inventory in parent training: Factor structure and longitudinal invariance. AB - OBJECTIVE: The purposes of the present study were twofold: (a) to examine the factor structure of the Working Alliance Inventory, Short (WAI-S) and (b) to investigate if factor loadings and thresholds fulfilled properties of longitudinal measurement invariance across two waves of data. METHOD: The study sample consisted of 259 Norwegian parents receiving Parent Management Training, the Oregon model. Parents rated alliance at sessions 3 and 12 during the therapy. Confirmatory factor analyses to assess the fit of a one-, two-, and three-factor model were performed using robust weighted least squares estimation for categorical indicators. RESULTS: The results showed that data provided best fit for the three-factor solution with goal, task, and bond. Furthermore, results demonstrated satisfactory invariance for factor loadings and thresholds across time. CONCLUSIONS: Overall, the results indicate that the WAI-S three-factor solution has acceptable psychometric properties for longitudinal measurement comparisons. PMID- 26828131 TI - Surgical resection of pancreatic head cancer: What is the optimal extent of surgery? AB - Extent of surgery should depend on curability. Improvements in surgical techniques have resulted in surgeons seeking to perform more radical surgery. To date, five randomized controlled trials (RCT) have analyzed the benefits of extended lymphadenectomy for pancreatic head cancer, but none has shown that extended lymphadenectomy enhances patient survival. As most patients with pancreatic cancer have microscopic, locally advanced disease that cannot be cured by surgery alone, local tumor control by extended lymphadenectomy cannot overcome the negative aspects of pre-existing lymph node metastasis. The most important factor improving overall survival following pancreatoduodenectomy in patients with pancreatic head cancer is proper systemic control of the disease rather than extensive local control. The long-term survival outcomes following adjuvant treatment in a large multi-center RCT suggest the need for aggressive systemic treatment. More attention must be paid to the benefits of adjuvant treatment, not only focusing on technical R0 resection. Surgical strategies for patients with pancreatic head cancer require more flexibility, with extent of surgery customized to individual patients, depending on tumor location and disease severity. PMID- 26828132 TI - Protein glycosylation in gastric and colorectal cancers: Toward cancer detection and targeted therapeutics. AB - Glycosylation is the most frequent and structurally complex posttranslational modification in cell-surface and secreted proteins. Glycans are major orchestrators of biological processes, namely, by controlling protein folding and key biological functions such as cell adhesion, migration, signaling and immune recognition. Altered glycosylation is considered a hallmark of malignant transformations that decisively contributes to disease outcome. This review comprehensively summarizes the main findings related with gastrointestinal cancers and the decisive impact of aberrant glycosylation on tumor biology toward more aggressive phenotypes. Particular emphasis is given to alterations in O glycosylation, namely, the overexpression of immature O-glycans, and the sialylated Lewis antigens sialyl-LeA and sialyl-LeX, frequently implicated in lymphohematogenous metastasis. We further discuss how recent contributions from glycoproteomics and glycoengineering fields have broadened our understanding of the human O-glycoproteome and its implications for cancer research. Finally, we address the tremendous potential of glycans in the context of targeted therapeutics (selective inhibition of glycosylation pathways, immunotherapy) and discuss the need to include glycomics/glycoproteomics in holistic panomics models toward true precision medicine settings. PMID- 26828134 TI - Patient-derived xenograft models of squamous cell carcinoma of the uterine cervix. AB - Patient-derived xenograft (PDX) models of cancer are considered to reflect the biology and treatment response of human tumors to a larger extent than xenograft models initiated from established cell lines. The characterization of a panel of four novel PDX models of cervical carcinoma of the uterine cervix is described in this communication. The outcome of treatment differed substantially among the donor patients, and the PDX models were found to mirror the histology, aggressiveness, and metastatic propensity of the donor patients' tumors. Two of the models (BK-12 and LA-19) were highly metastatic, one model (ED-15) was poorly metastatic, and one model (HL-16) was non-metastatic. The primary tumors of the two highly metastatic models showed high density of intratumoral lymphatics, whereas the other two models did not develop intratumoral lymphatics. The potential of the models to metastasize to lymph nodes was associated with high expression of both angiogenesis-related genes and cancer stem cell-related genes. The models may be highly valuable for studying mechanisms linking lymph node metastasis to lymphangiogenesis, hemangiogenesis, and the presence of cancer stem cells. PMID- 26828133 TI - Comprehensive molecular tumor profiling in radiation oncology: How it could be used for precision medicine. AB - New technologies enabling the analysis of various molecules, including DNA, RNA, proteins and small metabolites, can aid in understanding the complex molecular processes in cancer cells. In particular, for the use of novel targeted therapeutics, elucidation of the mechanisms leading to cell death or survival is crucial to eliminate tumor resistance and optimize therapeutic efficacy. While some techniques, such as genomic analysis for identifying specific gene mutations or epigenetic testing of promoter methylation, are already in clinical use, other "omics-based" assays are still evolving. Here, we provide an overview of the current status of molecular profiling methods, including promising research strategies, as well as possible challenges, and their emerging role in radiation oncology. PMID- 26828135 TI - Global trends in incidence and mortality of nasopharyngeal carcinoma. AB - Nasopharyngeal carcinoma (NPC) is a rare malignancy with an extraordinarily skewed geographic distribution worldwide. Although decreasing trends in incidence and mortality of NPC have been sporadically reported in some high-risk areas, no comprehensive description of the global trends has ever been made. We accessed incidence (1970-2007) and mortality (1970-2013) data from multiple sources, with the main ones being the Cancer Incidence in Five Continents (CI5) series and the World Health Organization (WHO) cancer mortality database. During the entire period studied, age-standardized incidence rates (ASIRs) of NPC decreased significantly in southern and eastern Asia, north America and Nordic countries with average annual percent changes (AAPCs) of -0.9% to -5.4% in males and -1.1% to -4.1% in females. Declines in age-standardized mortality rates (ASMRs) are even more remarkable and extensive, with AAPCs varying from -0.9% and -0.8% to 3.7% and -6.5% in males and females, respectively. Decreasing trends in NPC incidence are probably due to tobacco control, changes in diets and economic development. Declines in mortality rates are the results of advancements in diagnostic and radiotherapy techniques, as well as decreased incidence rates. PMID- 26828136 TI - A novel cell cycle-associated lncRNA, HOXA11-AS, is transcribed from the 5-prime end of the HOXA transcript and is a biomarker of progression in glioma. AB - The comprehensive lncRNA expression signature in glioma has not yet been fully elucidated. We performed a high-throughput microarray to detect the ncRNA expression profiles of 220 human glioma tissues. Here, we found that a novel lncRNA, HOXA11-AS, was the antisense transcript of the HOX11 gene. It was shown that HOXA11-AS was closely associated with glioma grade and poor prognosis. Multivariate Cox regression analysis revealed that HOXA11-AS was an independent prognostic factor in glioblastoma multiforme patients, and its expression was correlated with the glioma molecular subtypes of the Cancer Genome Atlas. Gene set enrichment analysis indicated that the gene sets most correlated with HOXA11 AS expression were involved in cell cycle progression. Over-expression of the HOXA11-AS transcript promoted cell proliferation in vitro, while knockdown of HOXA11-AS expression repressed cell proliferation via regulation of cell cycle progression. The growth-promoting and growth-inhibiting effects of HOXA11-AS were also demonstrated in a xenograft mouse model. Our data confirms, for the first time, that HOXA11-AS is an important long non-coding RNA that primarily serves as a prognostic factor for glioma patient survival. HOXA11-AS could serve as a biomarker for identifying glioma molecular subtypes and as therapeutic target for glioma patients. PMID- 26828137 TI - Oxidative stress markers are elevated in exhaled breath condensate of workers exposed to nanoparticles during iron oxide pigment production. AB - Markers of oxidative stress and inflammation were analysed in the exhaled breath condensate (EBC) and urine samples of 14 workers (mean age 43 +/- 7 years) exposed to iron oxide aerosol for an average of 10 +/- 4 years and 14 controls (mean age 39 +/- 4 years) by liquid chromatography-electrospray ionization-mass spectrometry/mass spectrometry (LC-ESI-MS/MS) after solid-phase extraction. Aerosol exposure in the workplace was measured by particle size spectrometers, a scanning mobility particle sizer (SMPS) and an aerodynamic particle sizer (APS), and by aerosol concentration monitors, P-TRAK and DustTRAK DRX. Total aerosol concentrations in workplace locations varied greatly in both time and space. The median mass concentration was 0.083 mg m(-3) (IQR 0.063-0.133 mg m(-3)) and the median particle concentration was 66 800 particles cm(-3) (IQR 16,900-86,900 particles cm(-3)). In addition, more than 80% of particles were smaller than 100 nm in diameter. Markers of oxidative stress, malondialdehyde (MDA), 4-hydroxy trans-hexenale (HHE), 4-hydroxy-trans-nonenale (HNE), 8-isoProstaglandin F2alpha (8-isoprostane) and aldehydes C6-C12, in addition to markers of nucleic acid oxidation, including 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8 OHG), 5-hydroxymethyl uracil (5-OHMeU), and of proteins, such as o-tyrosine (o Tyr), 3-chlorotyrosine (3-ClTyr), and 3-nitrotyrosine (3-NOTyr) were analysed in EBC and urine by LC-ESI-MS/MS. Almost all markers of lipid, nucleic acid and protein oxidation were elevated in the EBC of workers comparing with control subjects. Elevated markers were MDA, HNE, HHE, C6-C10, 8-isoprostane, 8-OHdG, 8 OHG, 5-OHMeU, 3-ClTyr, 3-NOTyr, o-Tyr (all p < 0.001), and C11 (p < 0.05). Only aldehyde C12 and the pH of samples did not differ between groups. Markers in urine were not elevated. These findings suggest the adverse effects of nano iron oxide aerosol exposure and support the utility of oxidative stress biomarkers in EBC. The analysis of urine oxidative stress biomarkers does not support the presence of systemic oxidative stress in iron oxide pigment production workers. PMID- 26828138 TI - The two fold role of oxytocin in social developmental disorders: A cause and a remedy? AB - Oxytocin is widely used by obstetricians to induce or facilitate labor. The long lasting consequences of oxytocin administration remain however unknown. Here, we discuss recent evidence suggesting a link between oxytocin labor induction and developmental social impairments such as autism spectrum disorders (ASD). Because these associations are methodologically questionable, we provide a review of animal studies investigating the long term effects of neonatal injection of oxytocin to shed light on the biological mechanisms that mediate the contribution of early oxytocin supplementation on the development of social impairments. In contrast to this potential negative impact on development, oxytocin has been shown to ameliorate social skills of ASD patients. However, results of chronic oxytocin administration from animal experiments are contradictory. We also review recent studies looking at chronic oxytocin effects in animal and in humans. Obstetric and psychiatric uses of exogenous oxytocin both impact on oxytocinergic neurotransmission but the effects may be sharply dissimilar. PMID- 26828139 TI - 18F-FDG PET/CT Diagnosis of Bronchopulmonary Carcinoids Versus Pulmonary Hamartomas. AB - PURPOSE: Radiological characterization of pulmonary tumors may be difficult and invasive. Needle biopsy may produce false-negative results. 18F-FDG PET/CT is an established noninvasive procedure for lung tumor characterization and staging. This study was aimed at differentiating bronchopulmonary carcinoids from hamartomas and typical from atypical bronchopulmonary carcinoids by means of 18F FDG PET/CT. PATIENTS AND METHODS: In a retrospective analysis of 118 patients, with surgically resected pulmonary carcinoid tumors and hamartomas, 87 of those selected had also undergone 18F-FDG PET/CT preoperatively and constituted the study population. To better assess the tracer accumulation, especially in small lesions, the 18F-FDG uptake (SUV) in the tumors was corrected for partial volume effect by applying recovery coefficients corresponding to the respective various specific tumor volumes, as extrapolated from those obtained from experiments in a NEMA phantom. RESULTS: The SUVmax was higher in the pulmonary carcinoids (mean, 3.9) than in the hamartomas (mean, 1.4; P <= 0.00001) and higher in the subgroup of peripheral carcinoids than in hamartomas (P <= 0.00001). The SUVmax was similar for the atypical and typical carcinoids, 5.0 and 3.8, respectively, because of the large variation in the data (P = 0.11). CONCLUSIONS: Using PET measurements of the 18F-FDG uptake (SUVmax) in the tumors, corrected for partial volume effects, it was possible to differentiate the carcinoids from the hamartomas, but the clinically more aggressive atypical carcinoids could not be differentiated from the typical carcinoids. PMID- 26828141 TI - Skeletal Tumor Burden on Baseline 18F-Fluoride PET/CT Predicts Bone Marrow Failure After 223Ra Therapy. AB - PURPOSE: Determine if skeletal tumor burden on 18F-fluoride PET/CT (fluoride PET/CT) predicts the risk of bone marrow failure (BMF) after 223Ra dichloride therapy (223Ra). METHODS: Forty-one metastatic prostate cancer patients (43-89 years old; mean, 71 +/- 9 years.) underwent fluoride PET/CT prior to 223Ra. Bone marrow failure was the primary end point and was defined as (1) development of hematologic toxicity (World Health Organization grade 3 or 4) associated with no recovery after 6 weeks or (2) death due to BMF after the last 223Ra dose. Bone marrow failure was correlated to fluoride PET/CT skeletal tumor burden (TLF10 [total lesion on fluoride PET/CT with SUVmax of 10 or greater]), use of chemotherapy, serum hemoglobin concentration, serum ALP, and serum prostate specific antigen. RESULTS: The number of 223Ra cycles ranged from 2 to 6 (mean, 5). Of the 41 patients, 16 developed BMF (G3 = 12; G4 = 4). A significantly increased risk of developing BMF was observed in patients with TLF10 of 12,000 or greater (hazard ratio [HR], 11.09; P < 0.0001), hemoglobin of less than 10 g/dL (HR, 7.35; P = 0.0002), and AP > 146 UI/L (HR, 4.52; P = 0.0100). Neither concomitant (HR, 0.91; P = 0.88) nor subsequent use of chemotherapy (HR, 0.14; P = 0.84) increased the risk of BMF, nor was prostate-specific antigen greater than 10 MUg/L (HR, 0.90; P = 0.86). Moreover, in a multivariable analysis, TLF10 was the only independent predictor of BMF (HR, 6.66; P = 0.0237). CONCLUSIONS: 223Ra was beneficial and reduced the risk of death even in patients with a high skeletal tumor burden. Fluoride PET/CT is able to determine which patients will benefit from 223Ra and which will develop BMF. PMID- 26828140 TI - Rapidly Growing Chest Wall Mass in a Case of Sporadic Metastatic Paraganglioma: Imaging With 4 Different PET Radiopharmaceuticals. AB - Pheochromocytomas/paragangliomas (PGLs) are rare tumors and mostly benign. We report on a 32-year-old woman with metastatic PGL who was first diagnosed with an abdominal PGL at the age of 12 years. She soon developed metastatic disease and received several treatments including external beam radiation and chemotherapy. When she was referred to our institution in 2014, her major complaint was a rapidly growing chest wall mass on the left side. The patient was imaged at our institution with 4 different PET radiopharmaceuticals. PMID- 26828143 TI - Primary Squamous Cell Carcinoma of Trachea Arising 4 Years After Radioiodine Treatment of Papillary Carcinoma of Thyroid. AB - Primary squamous cell carcinoma (SCC) of the trachea is rare. Here, we presented a rare case of primary SCC of the trachea arising 4 years after radioiodine (RAI) treatment of papillary carcinoma of the thyroid. In this case, concomitant uptake of I-RAI and F-FDG was demonstrated in the thyroidal mass with tracheal invasion, which mimicked mixed well-differentiated and dedifferentiated thyroid carcinoma. The diagnosis of SCC of the trachea was made only after tracheal biopsy. This case illustrates that FDG-avid thyroid bed lesion, in the presence of thyroid carcinoma, may not necessarily be related to the thyroid pathology. PMID- 26828142 TI - Massive Pelvic Lymphadenopathy Due to Recurrent Non-Hodgkin Lymphoma Incidentally Revealed on a 99mTc-MDP Bone Scintigraphy. AB - A 58-year-old man underwent Tc-MDP bone scintigraphy to evaluate the cause of diffuse bone pain. The images did not identify the exact cause of his symptoms. However, a "light bulb"-shaped urinary bladder and diffused increased activity in the scrotal region and left thigh were noted, which suggest a mass effect in the pelvis. A CT scan of the pelvis revealed soft tissue compressing the urinary bladder. A diagnosis of recurrent lymphoma was made. PMID- 26828145 TI - FDG PET/CT Evidence of Effective Treatment of Cardiac Sarcoidosis With Adalimumab. AB - A 53-year-old man with mediastinal lymph node biopsy and cardiac MRI-proven cardiac sarcoidosis (CS) received treatment with pacemaker and steroids. FDG PET/CT showed active CS despite treatment with prednisone and methotrexate. Addition of weekly adalimumab (Humira) injections was introduced for 3 months. Follow-up FDG PET/CT showed complete resolution of CS as well as improvement of other sarcoid lesions in the thoracic lymph nodes. PMID- 26828144 TI - Elevated 68Ga Prostate-Specific Membrane Antigen Activity in Metastatic Non-Small Cell Lung Cancer. AB - A 71-year-old man with a background of treated stage IIIB non-small cell lung cancer was referred for Ga prostate-specific membrane antigen (PSMA) PET/CT for staging of prostate cancer. In addition to the PSMA uptake in the known prostate malignancy, the study also demonstrated increased PSMA uptake in an enlarging left lower lobe lung mass with diffusely increased PSMA uptake in an enlarged thyroid gland and bilateral enlarged supraclavicular lymph nodes. Fine-needle aspiration biopsy of the thyroid gland and a left supraclavicular lymph node demonstrated metastatic adenocarcinoma from a primary lung cancer. PMID- 26828146 TI - Pituitary Prolactinoma Imaged by 99mTc-Sestamibi SPECT/CT in a Multiple Endocrine Neoplasia Type 1 Patient. AB - A 35-year-old woman who had undergone bilateral inferior parathyroidectomy for primary hyperparathyroidism was referred to our hospital to evaluate the cause of irregular menses, galactorrhea, and paroxysmal headache. Multiple endocrine neoplasia type 1 was then suspected for the high levels of plasma prolactin, parathyroid hormone, serum calcium, insulin, and related symptoms. A Tc-sestamibi SPECT/CT acquired to evaluate parathyroid glands unexpectedly revealed an increased accumulation in the pituitary gland, which was further confirmed by enhanced magnetic resonance imaging as a pituitary microadenoma. Bromocriptine treatment gradually reduced the prolactin level. PMID- 26828147 TI - Measurement of Renal Depth in Dynamic Renal Scintigraphy Using Ultralow-Dose CT. AB - PURPOSE: Renal depths predicted using predefined formulas are commonly used for camera-based evaluation of renal function. We investigated the feasibility and utility of renal depth measurement using ultralow-dose CT images acquired in conjunction with dynamic renal scintigraphy. METHODS: Dynamic renal scintigraphy with Tc-MAG3 was performed in 117 patients (225 kidneys) using a SPECT/CT scanner, and ultralow-dose CT (estimated effective dose of 0.17 mSv) was performed during free breathing immediately before tracer injection. The clarity of the renal contour on the CT images was evaluated visually. The renal depths were measured by 2 methods and compared with depths predicted by 2 previously reported methods. The accuracy of camera-based clearance using predicted and measured depths was evaluated using a single-sample method as a standard. RESULTS: The clarity of the renal contour was poor in 18 of 225 kidneys, and 12 of 117 patients were considered ineligible for depth measurement. The measurement for eligible patients showed excellent intraobserver and interobserver repeatabilities. Although mean depths were similar among the 2 CT measurement methods and 2 prediction methods, absolute differences of more than 1 cm were observed in approximately 20% of kidneys between CT measurement and prediction. CT measurement of renal depth failed to improve the accuracy of camera-based clearance evaluation. CONCLUSION: Ultralow-dose CT allowed measurement of renal depth in most patients. Substantial differences in renal depth between prediction and CT measurement indicated potential usefulness of CT measurement, although no actual improvement in the accuracy of clearance estimation was demonstrated in this study. PMID- 26828148 TI - Gangrenous Leg in a Patient With Diabetes on MDP Bone Scintigraphy. AB - Diabetic patients with peripheral arterial disease frequently experience gangrene of the lower limbs. It has been suggested that a bone scan is useful in differentiating viable from nonviable tissues in patients with extensive peripheral gangrene and thus can help determine the appropriate level of amputation in such patients. We present a 68-year-old diabetic woman with right breast cancer, who was referred to our facility for a bone scan as part of her metastatic workup. Bone scan findings revealed absolute photon deficiency in the distal half of her left lower limb. PMID- 26828150 TI - EPR studies on the kinetics of the alpha-hydroxyethyl radical generated by Fenton like chemistry. AB - Flow systems, either stopped or continuous, have long been at the core of kinetic studies of chemical reactions. Such flow systems need to be coupled with appropriate spectroscopic or otherwise techniques for the detection of the chemical species studied. If paramagnetic species are formed or consumed during the investigated reaction, electron paramagnetic resonance (EPR) with its nanomolar sensitivity can be the spectroscopic method of choice. However, not much literature is available on the application of EPR to quantitatively study kinetics of chemical reactions in the liquid state. Herein, we report the characterisation of the commercially available mixing resonator ER 4117 MX from Bruker using the TEMPO-dithionite reaction as a standard. Furthermore, this setup was used to study the kinetics of the Fenton-like system of TiCl3/H2O2 and ethanol forming thealpha-hydroxyethyl radical. Potential contributions of reactions with O2, H2O2, Ti(3+/4+), and self-recombination in the decay of thealpha-hydroxyethyl radical were investigated and the bimolecular decay was shown to be the dominant decay pathway, with a decay rate constant of 6.6*10(8) M(-1) s(-1). This study shows the effectiveness and capabilities of EPR as a direct, sensitive and in-situ method in kinetic studies. PMID- 26828149 TI - Initial Staging of Locally Advanced Rectal Cancer and Regional Lymph Nodes: Comparison of Diffusion-Weighted MRI With 18F-FDG-PET/CT. AB - PURPOSE: The aim of the study was to compare diffusion-weighted MRI (DW-MRI) parameters with 18F-FDG PET/CT in primary locally advanced rectal cancer (LARC). METHODS: From October 2012 to September 2014, 24 patients with histologically confirmed and untreated LARC (T3-T4) prospectively underwent a pelvic 1.5-T DW MRI (b = 0 s/mm, b = 600 s/mm2) and a whole-body 18F-FDG PET/CT, before neoadjuvant therapy. The 2 examinations were performed on the same day. Two readers measured 18F-FDG SUVmax and SUVmean of the rectal tumor and of the pathological regional lymph nodes on PET/CT and compared these with minimum and mean values of the ADC (ADCmin and ADCmean) on maps generated from DW-MRI. The diagnostic performance of ADC values in identifying pathological lymph nodes was also assessed. RESULTS: Regarding tumors (n = 24), we found a significant negative correlation between SUVmean and corresponding ADCmean values (rho = 0.61, P = 0.0017) and between ADCmin and SUVmax (rho = -0.66, P = 0.0005). Regarding the lymph nodes (n = 63), there was a significant negative correlation between ADCmean and SUVmean values (rho = -0.38, P = 0.0021), but not between ADCmin and SUVmax values (rho = -0.11, P = 0.41). Neither ADCmean nor ADCmin values helped distinguish pathological from benign lymph nodes (AUC of 0.24 [confidence interval, 0.10-0.38] and 0.41 [confidence interval, 0.22-0.60], respectively). CONCLUSIONS: The correlations between ADCmean and SUVmean suggest an association between tumor cellularity and metabolic activity in untreated LARC and in regional lymph nodes. However, compared with 18F-FDG PET/CT, ADC values are not reliable for identifying pathological lymph nodes. PMID- 26828151 TI - The maternal brain under stress: Consequences for adaptive peripartum plasticity and its potential functional implications. AB - The peripartum period represents a time during which all mammalian species undergo substantial physiological and behavioural changes, which prepare the female for the demands of motherhood. In addition to behavioural and physiological alterations, numerous brain regions, such as the medial prefrontal cortex, olfactory bulb, medial amygdala and hippocampus are subject to substantial peripartum-associated neuronal, dendritic and synaptic plasticity. These changes, which are temporally- and spatially-distinct, are strongly influenced by gonadal and adrenal hormones, such as estrogen and cortisol/corticosterone, which undergo dramatic fluctuations across this period. In this review, we describe our current knowledge regarding these plasticity changes and describe how stress affects such normal adaptations. Finally, we discuss the mechanisms potentially underlying these neuronal, dendritic and synaptic changes and their functional relevance for the mother and her offspring. PMID- 26828153 TI - A Young Scientist on a Journey of Discovery. PMID- 26828152 TI - Combination of counter current salting-out homogenous liquid-liquid extraction and dispersive liquid-liquid microextraction as a novel microextraction of drugs in urine samples. AB - The counter current salting-out homogenous liquid-liquid extraction (CCSHLLE) joined with the dispersive liquid-liquid microextraction based on solidification of floating organic drop (DLLME-SFO) has been developed as a high preconcentration technique for the determination of different drugs in urine samples. Amphetamines were employed as model compounds to assess the extraction procedure and were determined by high performance liquid chromatography ultraviolet detection (HPLC-UV). In this method, initially, NaCl as a separation reagent is filled into a small column and a mixture of urine and acetonitrile is passed through the column. By passing the mixture, NaCl is dissolved and the fine droplets of acetonitrile are formed due to salting-out effect. The produced droplets go up through the remained mixture and collect as a separated layer. Then, the collected acetonitrile is removed with a syringe and mixed with 30.0MUL 1-undecanol (extraction solvent). In the second step, the 5.00mLK2CO3 solution (2% w/v) is rapidly injected into the above mixture placed in a test tube for further DLLME-SFO. Under the optimum conditions, calibration curves are linear in the range of 1-3000MUgL(-1) and limit of detections (LODs) are in the range of 0.5-2MUgL(-1). The extraction recoveries and enrichment factors ranged from 78 to 84% and 157 to 168, respectively. Repeatability (intra-day) and reproducibility (inter-day) of method based on seven replicate measurements of 100MUgL(-1) of amphetamines were in the range of 3.5-4.5% and 4-5%, respectively. The method was successfully applied for the determination of amphetamines in the actual urine samples. The relative recoveries of urine samples spiked with amphetamine and methamphetamine are 90-108%. PMID- 26828154 TI - Soil in the City: Sustainably Improving Urban Soils. AB - Large tracts of abandoned urban land, resulting from the deindustrialization of metropolitan areas, are generating a renewed interest among city planners and community organizations envisioning the productive use of this land not only to produce fresh food but to effectively manage stormwater and mitigate the impact of urban heat islands. Healthy and productive soils are paramount to meet these objectives. However, these urban lands are often severely degraded due to anthropogenic activities and are generally contaminated with priority pollutants, especially heavy metals and polycyclic aromatic hydrocarbons. Characterizing these degraded and contaminated soils and making them productive again to restore the required ecosystem services was the theme of the "Soil in the City- 2014" conference organized by W-2170 Committee (USDA's Sponsored Multi-State Research Project: Soil-Based Use of Residuals, Wastewater, & Reclaimed Water). This special section of comprises 12 targeted papers authored by conference participants to make available much needed information about the characteristics of urban soils. Innovative ways to mitigate the risks from pollutants and to improve the soil quality using local resources are discussed. Such practices include the use of composts and biosolids to grow healthy foods, reclaim brownfields, manage stormwater, and improve the overall ecosystem functioning of urban soils. These papers provide a needed resource for educating policymakers, practitioners, and the general public about using locally available resources to restore fertility, productivity, and ecosystem functioning of degraded urban land to revitalize metropolitan areas for improving the overall quality of life for a large segment of a rapidly growing urban population. PMID- 26828155 TI - Spatial Patterns of Heavy Metal Contamination by Urbanization. AB - Spatial analysis of heavy metals (HMs) is an important step toward developing predictive models of urban HM contamination. This study assessed the spatial distribution of the enrichment of eight HMs (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in the city of Ghent, Belgium. A database with soil HM concentrations measured at 2194 point observations was collected from the Public Waste Agency of Flanders. The degree of anthropogenic HM enrichment was quantified using an urban pollution index (PI). Enrichment of HMs showed high variations throughout the study area. Observed concentrations of As, Cd, Cr, and Hg did not exceed expected background values for the majority of the sampling locations (PI <= 1 for 76% [As], 64% [Cd], 50% [Cr], and 74% [Hg] of sampling points). Accordingly, predicted PI values of these HMs in Ghent were on average <2. On the other hand, observed median PIs for Cu, Ni, Pb, and Zn surpassed expected background values (PI >1) in 66, 76, 68, and 66% of the cases. The predicted PI means for the entire study area were 3.46 (Cu), 2.06 (Ni), 3.26 (Pb), and 3.28 (Zn). Comparison between various land use types and times since development indicated that HM enrichment was generally highest in urban land uses built up before 1933. Results, however, suggested that spatial patterns of HM contamination are difficult to predict in cities with a long history of industrialization without knowledge on the spatial distribution of (potentially) contaminating historical industrial activities. PMID- 26828156 TI - Soil Quality Assessment Is a Necessary First Step for Designing Urban Green Infrastructure. AB - This paper describes the results of a preliminary project conducted by a team of DePaul University undergraduate students and staff from the Gary Comer Youth Center located on Chicago's South Side. The team assessed soil quality on 116 samples collected among four abandoned residential lots adjacent to the Comer Center. Soil quality data will be used in a follow-up study to determine the suitability of each lot for green infrastructure implementation. Green infrastructure may be a useful approach for providing ecosystem services and mitigating food deserts in inner-city communities. Soil quality on all lots was poor. All soils had pH >8.0, low biological activity, and low N mineralization potential. The soils were rich in available P and had mean total Pb concentrations above the USEPA threshold (400 mg kg) for children's playlots. Mean bioavailable Pb on the largest of the four lots was 12% of total Pb, indicating that most of the total Pb is not bioavailable. This result is encouraging because high bioavailable Pb concentrations are linked with negative health effects, particularly in children. All lots had NO-N concentrations below those considered to be appropriate for plant growth. On the other hand, no significant differences in mean concentrations of the other analytes were found. The poor soil quality in the four lots presents an opportunity to use green infrastructure to enhance ecosystem services, improve community and environmental health, and provide more equitable access to green space. PMID- 26828157 TI - Lead in Urban Soils: A Real or Perceived Concern for Urban Agriculture? AB - Urban agriculture is growing in cities across the United States. It has the potential to provide multiple benefits, including increased food security. Concerns about soil contamination in urban areas can be an impediment to urban agriculture. Lead is the most common contaminant in urban areas. In this paper, direct (soil ingestion via outdoor and indoor exposure) and indirect (consumption of food grown in Pb-contaminated soils) exposure pathways are reviewed. It is highly unlikely that urban agriculture will increase incidences of elevated blood Pb for children in urban areas. This is due to the high likelihood that agriculture will improve soils in urban areas, resulting in reduced bioavailability of soil Pb and reduced fugitive dust. Plant uptake of Pb is also typically very low. The exceptions are low-growing leafy crops where soil-splash particle contamination is more likely and expanded hypocotyl root vegetables (e.g., carrot). However, even with higher bioaccumulation factors, it is not clear that the Pb in root vegetables or any other crops will be absorbed after eating. Studies have shown limited absorption of Pb when ingested with food. Best management practices to assure minimal potential for exposure are also common practices in urban gardens. These include the use of residuals-based composts and soil amendments and attention to keeping soil out of homes. This review suggests that benefits associated with urban agriculture far outweigh any risks posed by elevated soil Pb. PMID- 26828158 TI - Phosphorus Amendment Efficacy for In Situ Remediation of Soil Lead Depends on the Bioaccessible Method. AB - A validated method is needed to measure reductions of in vitro bioaccessible (IVBA) Pb in urban soil remediated with amendments. This study evaluated the effect of in vitro extraction solution pH and glycine buffer on bioaccessible Pb in P-treated soils. Two Pb-contaminated soils (790-1300 mg Pb kg), one from a garden and one from a city lot in Cleveland, OH, were incubated in a bench scale experiment for 1 yr. Six phosphate amendments, including bone meal, fish bone, poultry litter, monoammonium phosphate, diammonium phosphate, and triple superphosphate, were added to containers at two application rates. Lead IVBA was assessed using USEPA Method 1340 and three modified versions of this method. Modifications included using solutions with pH 1.5 and 2.5 as well as using solutions with and without 0.4 mol L glycine. Soil amendments were ineffective in reducing IVBA Pb in these soils as measured by pH 1.5 with glycine buffer. The greatest reductions in IVBA Pb, from 5 to 26%, were found using pH 2.5 extractions. Lead mineral results showed several soil amendments promoted Pb phosphate formation, an indicator of remediation success. A significant negative linear relationship between reduction in IVBA Pb and Pb-phosphate formation was found only for pH 2.5 without glycine extraction solution. A modified USEPA Method 1340 without glycine and using pH 2.5 has the potential to predict P soil treatment efficacy and reductions in bioavailable Pb. PMID- 26828159 TI - Impact of Residential Prairie Gardens on the Physical Properties of Urban Soil in Madison, Wisconsin. AB - Prairie gardens have become a common addition to residential communities in the midwestern United States because prairie vegetation is native to the region, requires fewer resources to maintain than turfgrass, and has been promoted to help remediate urban soil. Although prairie systems typically have deeper and more diverse root systems than traditional turfgrass, no one has tested the effect of this vegetation type on the physical properties of urban soil. We hypothesized that residential prairie gardens would yield lower soil bulk density (BD), lower penetration resistance (PR), greater soil organic matter (SOM), and greater saturated hydraulic conductivity () compared with turfgrass lawns. To test this hypothesis, we examined 12 residential properties in Madison, WI, where homeowners had established a prairie garden within their turfgrass lawn. Despite a consistent trend in the difference between vegetation types, no significant main effects were found (i.e., a difference between vegetation types when averaged over depth) for any of the four soil properties measured in this study. Differences were found with depth and depended on a significant interaction with vegetation type. At the surface depth (0-0.15 m), soil beneath prairie gardens had 10% lower mean BD, 15% lower mean PR, 25% greater level of SOM, and 33% greater compared with soil beneath the adjacent lawns. These differences were not detected at deeper sampling intervals of 0.15 to 0.30 m and 0.30 to 0.45 m. Although not statistically significant, the consistent trend and direction among soil variables suggest that residential prairie gardens had changed the surface soil at a rate that marginally outpaced turfgrass and calls for controlled experiments to identify the mechanisms that might enhance these trends. PMID- 26828160 TI - Greening a Steel Mill Slag Brownfield with Biosolids and Sediments: A Case Study. AB - The former US Steel Corporation's South Works site in Chicago, IL, is a 230-ha bare brownfield consisting of steel mill slag fill materials that will need to be reclaimed to support and sustain vegetation. We conducted a case study to evaluate the suitability of biosolids and dredged sediments for capping the steel mill slag to establish good quality turfgrass vegetation. Eight study plots were established on a 0.4-ha parcel that received biosolids and dredged sediment blends of 0, 25, 50, or 100% biosolids (v/v). Turfgrass was successfully established and was thicker and greener in biosolids-amended sediments than in unamended sediments. Concentrations of N, P, K, and micronutrients in turfgrass tissues increased with increasing biosolids. Soil organic carbon, N, P, and micronutrients increased with increasing biosolids. Cadmium, Cu, Ni, and Zn concentrations in biosolids-amended sediments also increased with increasing biosolids but were far below phytotoxicity limits for turfgrass. Lead and Cr concentrations in biosolids-amended plots were comparable to concentrations in unamended sediments. Groundwater monitoring lysimeters and wells below the study site and near Lake Michigan were not affected by nutrients leaching from the amendments. Overall, the results from this case study demonstrated that blends of biosolids and dredged sediments could be successfully used for capping steel mill slag brownfield sites to establish good quality turfgrass vegetation. PMID- 26828161 TI - Beneficial Use of Dredge Materials for Soil Reconstruction and Development of Dredge Screening Protocols. AB - Upland placement of dredge sediments has the potential to provide beneficial reuse of suitable sediments for agricultural uses or urban soil reconstruction. However, the use of many dredge materials is limited by contaminants, and most established screening protocols focus on limiting major contaminants such as heavy metals and polycyclic aromatic hydrocarbons and generally ignore fundamental agronomic parameters. Since 2001, we have placed over 450,000 m of Potomac River fresh water dredge materials and 250,000 m of saline materials from various locations into monitored confined upland facilities in Charles City, VA, and documented their conversion to agricultural uses. Groundwater and soil quality monitoring has indicated no adverse effects from material placement and outstanding agricultural productivity for the freshwater materials. Once placed, saline materials rapidly leach and ripen with quick declines in pH, electrical conductivity, and sodicity, but potentials for local groundwater impacts must be considered. Our experience to date indicates that the most important primary screening parameter is acid-base accounting (potential acidity or lime demand), which should become a mandatory analytical requirement. Our second level of acceptance screening is based on a combination of federal and state residual waste and soil screening standards and basic agronomic principles. High silt+clay and total organic C may also limit rapid use of many dredge materials due to extended dewatering times and physical limitations. This dredge material screening system separates potential upland placement candidates into three soil quality management categories (unsuitable, suitable, and clean fill) with differing monitoring requirements. Similar use of these sediments in urban soil reconstruction is also recommended. PMID- 26828162 TI - Restoring Ecosystem Function in Degraded Urban Soil Using Biosolids, Biosolids Blend, and Compost. AB - Many soils at former industrial sites are degraded. The objective of this research was to determine the ability of compost, biosolids, and biosolids blends to improve soil ecosystem function with minimal potential impact to surface water. Treatments rototilled into the top 12.5 cm of soil were biosolids at 202 Mg ha; biosolids at 404 Mg ha; compost at 137 Mg ha; or a blend consisting of biosolids applied at 202 Mg ha, drinking water treatment residual, and biochar. Rainfall runoff from experimental plots was collected for 3 yr. One year after soil amendments were incorporated, a native seed mix containing grasses, legumes, and forbs was planted. Soil amendments improved soil quality and nutrient pools, established a dense and high-quality vegetative cover, and improved earthworm reproductive measures. Amendments increased soil enzymatic activities that support soil function. Biosolids treatments increased the Shannon-Weaver Diversity Index for grasses. For the forbs group, control plots had the lowest diversity index and the biosolids blend had the highest diversity index. Biosolids and compost increased the number of earthworm juveniles. In general, biosolids outperformed compost. Biosolids increased N and P in rainfall runoff more than compost before vegetation was established. Several microconstituents (i.e., pharmaceutical and personal care products) were detected in runoff water but at concentrations below the probable no-effect levels and therefore should pose little impact to the aquatic environment. Future restoration design should ensure that runoff control measures are used to control sediment loss from the restored sites at least until vegetation is established. PMID- 26828163 TI - Mass Balance Model for Sustainable Phosphorus Recovery in a US Wastewater Treatment Plant. AB - In response to limited phosphorus (P) reserves worldwide, several countries have demonstrated the prospect of recovering significant amounts of P from wastewater treatment plants (WWTPs). This technique uses enhanced biological P removal (EBPR) to concentrate P in sludge followed by chemical precipitation of P as struvite, a usable phosphate mineral. The present study models the feasibility of this enhanced removal and recovery technique in a WWTP in Arizona with design parameters typical of infrastructure in the United States. A mass balance was performed for existing treatment processes and modifications proposed to estimate the quantity of P that could be recovered under current and future flow conditions. Modeling results show that about 71 to 96% of the P being lost potentially could be recovered as struvite. About 491 +/- 64 t yr of struvite may be recovered after process modification, which corresponds to $150,000 +/- $20,000 yr in P sales to fertilizer industries. The process was projected to be economically feasible, with a payback period of 45 +/- 30 yr in the studied WWTP and a much shorter duration of 3 +/- 1 yr for WWTPs already using an EBPR process. Furthermore, modeling results suggest that P recovery can improve the quality of biosolids by favorably reducing the P:N ratio. Implementation of this strategy at US WWTPs may increase national security by reducing dependence of limited P resources. Considering all aspects of the recovery process with respect to environmental, economic, and social implications, the examined technique is concluded to represent a cost-attractive and sustainable method for P management in US WWTPs. PMID- 26828164 TI - Urban Soil: Assessing Ground Cover Impact on Surface Temperature and Thermal Comfort. AB - The urban population growth, together with the contemporary deindustrialization of metropolitan areas, has resulted in a large amount of available land with new possible uses. It is well known that urban green areas provide several benefits in the surrounding environment, such as the improvement of thermal comfort conditions for the population during summer heat waves. The purpose of this study is to provide useful information on thermal regimes of urban soils to urban planners to be used during an urban transformation to mitigate surface temperatures and improve human thermal comfort. Field measurements of solar radiation, surface temperature (), air temperature (), relative humidity, and wind speed were collected on four types of urban soils and pavements in the city of Florence during summer 2014. Analysis of days under calm, clear-sky condition is reported. During daytime, sun-to-shadow differences for , apparent temperature index (ATI), and were significantly positive for all surfaces. Conversely, during nighttime, differences among all surfaces were significantly negative, whereas ATI showed significantly positive differences. Moreover, was significantly negative for grass and gravel. Relative to the shaded surfaces, was higher on white gravel and grass than gray sandstone and asphalt during nighttime, whereas gray sandstone was always the warmest surface during daytime. Conversely, no differences were found during nighttime for ATI and measured over surfaces that were exposed to sun during the day, whereas showed higher values on gravel than grass and asphalt during nighttime. An exposed surface warms less if its albedo is high, leading to a significant reduction of during daytime. These results underline the importance of considering the effects of surface characteristics on surface temperature and thermal comfort. This would be fundamental for addressing urban environment issues toward the heat island mitigation considering also the impact of urban renovation on microclimate. PMID- 26828165 TI - Stormwater Bioretention Systems: Testing the Phosphorus Saturation Index and Compost Feedstocks as Predictive Tools for System Performance. AB - A replicated column trial was conducted to evaluate the potential for the phosphorus saturation index (PSI) to predict P movement in bioretention soil mixtures (BSMs). The impact of compost feedstock on BSM performance was also evaluated. Three composts (biosolids/yard, yard/food waste, and manure/sawdust) were each brought to PSI values of 0.1, 0.5, and 1.0 through the addition of Fe based water treatment residuals (WTRs) to lower the PSI and P salts to increase the PSI. A synthetic stormwater solution was used for 12 leaching events. The PSI predicted total and dissolved P concentrations in column leachate. All composts removed P at PSI 0.1. All composts were a source of P for the higher PSI values tested, with P concentrations in the leachate decreasing over time. Ammonia and nitrate from all treatments decreased over time, with all treatments showing effective N removal. Copper removal (total and dissolved) was >90% for all treatments, with the highest removal observed at PSI 0.1 for all composts. Zinc removal (total) was also greatest in the 0.1 PSI for all composts. At PSI 0.5 and 1.0, the biosolids/yard compost was less effective than the other materials at removing Zn, with a removal efficiency of approximately 50%. Infiltration rates were similar across all treatments and ranged from 0.44 +/- 0.1 cm min in the manure/sawdust at PSI 0.1 to 3.8 +/- 2.8 cm min in the food/yard at PSI 1.0. Plant growth in the manure/sawdust compost was reduced in comparison to the other composts tested across all PSI levels. The results of this study indicate that the PSI may be an effective tool for predicting P movement in bioretention systems. Compost feedstock does not indicate the ability of composts to filter contaminants filtration, with all composts tested showing high contaminant removal. PMID- 26828166 TI - Elemental Concentrations in Urban Green Stormwater Infrastructure Soils. AB - Green stormwater infrastructure (GSI) is designed to capture stormwater for infiltration, detention, evapotranspiration, or reuse. Soils play a key role in stormwater interception at these facilities. It is important to assess whether contamination is occurring in GSI soils because urban stormwater drainage areas often accumulate elements of concern. Soil contamination could affect hydrologic and ecosystem functions. Maintenance workers and the public may also be exposed to GSI soils. We investigated soil elemental concentrations, categorized as macro and micronutrients, heavy metals, and other elements, at 59 GSI sites in the city of Philadelphia. Non-GSI soil samples 3 to 5 m upland of GSI sites were used for comparison. We evaluated differences in elemental composition in GSI and non GSI soils; the comparisons were corrected for the age of GSI facility, underlying soil type, street drainage, and surrounding land use. Concentrations of Ca and I were greater than background levels at GSI sites. Although GSI facilities appear to accumulate Ca and I, these elements do not pose a significant human health risk. Elements of concern to human health, including Cd, Hg, and Pb, were either no different or were lower in GSI soils compared with non-GSI soils. However, mean values found across GSI sites were up to four times greater than soil cleanup objectives for residential use. PMID- 26828167 TI - The Urban Forest and Ecosystem Services: Impacts on Urban Water, Heat, and Pollution Cycles at the Tree, Street, and City Scale. AB - Many environmental challenges are exacerbated within the urban landscape, such as stormwater runoff and flood risk, chemical and particulate pollution of urban air, soil and water, the urban heat island, and summer heat waves. Urban trees, and the urban forest as a whole, can be managed to have an impact on the urban water, heat, carbon and pollution cycles. However, there is an increasing need for empirical evidence as to the magnitude of the impacts, both beneficial and adverse, that urban trees can provide and the role that climatic region and built landscape circumstance play in modifying those impacts. This special section presents new research that advances our knowledge of the ecological and environmental services provided by the urban forest. The 14 studies included provide a global perspective on the role of trees in towns and cities from five continents. Some studies provide evidence for the cooling benefit of the local microclimate in urban green space with and without trees. Other studies focus solely on the cooling benefit of urban tree transpiration at a mesoscale or on cooling from canopy shade at a street and pedestrian scale. Other studies are concerned with tree species differences in canopy interception of rainfall, water uptake from biofilter systems, and water quality improvements through nutrient uptake from stormwater runoff. Research reported here also considers both the positive and the negative impacts of trees on air quality, through the role of trees in removing air pollutants such as ozone as well as in releasing potentially harmful volatile organic compounds and allergenic particulates. A transdisciplinary framework to support future urban forest research is proposed to better understand and communicate the role of urban trees in urban biogeochemical cycles that are highly disturbed, highly managed, and of paramount importance to human health and well-being. PMID- 26828168 TI - Thermal Influence of a Large Green Space on a Hot Urban Environment. AB - City-scale warming is becoming a serious problem in terms of human health. Urban green spaces are expected to act as a countermeasure for urban warming, and therefore better understanding of the micro-climate benefits of urban green is needed. This study quantified the thermal influence of a large green park in Tokyo, Japan on the surrounding urban area by collecting long-term measurements. Apparent variations in the temperature difference between the park and surrounding town were found at both the diurnal and seasonal scales. Advection by regional-scale wind and turbulent mixing transfers colder air from the park to urban areas in its vicinity. The extent of the park's thermal influence on the town was greater on the downwind side of the park (450 m) than on the upwind side (65 m). The extent was also greater in an area where the terrain slopes down toward the town. Even on calm nights, the extent of the thermal influence extended by the park breeze to an average of 200 m from the park boundary. The park breeze was characterized by its divergent flow in a horizontal plane, which was found to develop well in calm conditions late at night (regional scale wind <1.5 m s and after 02:00 LST). The average magnitude of the cooling effect of the park breeze was estimated at 39 Wm. This green space tempered the hot summer nights on a city block scale. These findings can help urban planners in designing a heat-adapted city. PMID- 26828169 TI - The Bigger, the Better? The Influence of Urban Green Space Design on Cooling Effects for Residential Areas. AB - It is well known that the cooling effect of an urban green space extends into its surroundings, cooling the immediate environment and mitigating urban heat problems. However, the effects of size, shape, and type of an urban green space on cooling remain uncertain. The objectives of our study were to quantify and compare the strength of the cooling effects of urban parks and forests, to determine how far the cooling effects extend into the surrounding residential environment, and to better understand how temperature gradients are driven by physical characteristics of the green space and the surroundings. Mobile air temperature measurements were performed in 62 urban parks and forests in the city of Leipzig, Germany, in the summer of 2013. Three indicators of cooling were calculated: the change in temperature (DeltaT) at the park-width distance, the maximum DeltaT, and the cooling distance. The relationships of these variables to the physical characteristics of the green spaces and their surroundings were examined in multiple regression models. Analyzing all three indicators revealed that cooling effects were greater in urban forests than in parks. Cooling increased with increasing size but in a different manner for forests and parks, whereas the influence of shape was the same for forests and parks. Generally, the characteristics of the green spaces were more important than the characteristics of the residential surroundings. These findings have the potential to assist in better planning and designing of urban green spaces to increase their cooling effects. PMID- 26828170 TI - Modeling Tree Shade Effect on Urban Ground Surface Temperature. AB - There is growing interest in the role that urban forests can play as urban microclimate modifiers. Tree shade and evapotranspiration affect energy fluxes and mitigate microclimate conditions, with beneficial effects on human health and outdoor comfort. The aim of this study was to investigate surface temperature () variability under the shade of different tree species and to test the capability in predicting of a proposed heat transfer model. Surface temperature data on asphalt and grass under different shading conditions were collected in the Cascine park, Florence, Italy, and were used to test the performance of a one dimensional heat transfer model integrated with a routine for estimating the effect of plant canopies on surface heat transfer. Shading effects of 10 tree species commonly used in Italian urban settings were determined by considering the infrared radiation and the tree canopy leaf area index (LAI). The results indicate that, on asphalt, was negatively related to the LAI of trees ( reduction ranging from 13.8 to 22.8 degrees C). On grass, this relationship was weaker probably because of the combined effect of shade and grass evapotranspiration on ( reduction ranged from 6.9 to 9.4 degrees C). A sensitivity analysis confirmed that other factors linked to soil water content play an important role in reduction of grassed areas. Our findings suggest that the energy balance model can be effectively used to estimate of the urban pavement under different shading conditions and can be applied to the analysis of microclimate conditions of urban green spaces. PMID- 26828171 TI - The Urban Tree as a Tool to Mitigate the Urban Heat Island in Mexico City: A Simple Phenomenological Model. AB - The urban heat island (UHI) is mainly a nocturnal phenomenon, but it also appears during the day in Mexico City. The UHI may affect human thermal comfort, which can influence human productivity and morbidity in the spring/summer period. A simple phenomenological model based on the energy balance was developed to generate theoretical support of UHI mitigation in Mexico City focused on the latent heat flux change by increasing tree coverage to reduce sensible heat flux and air temperature. Half-hourly data of the urban energy balance components were generated in a typical residential/commercial neighborhood of Mexico City and then parameterized using easily measured variables (air temperature, humidity, pressure, and visibility). Canopy conductance was estimated every hour in four tree species, and transpiration was estimated using sap flow technique and parameterized by the envelope function method. Averaged values of net radiation, energy storage, and sensible and latent heat flux were around 449, 224, 153, and 72 W m, respectively. Daily tree transpiration ranged from 3.64 to 4.35 Ld. To reduce air temperature by 1 degrees C in the studied area, 63 large would be required per hectare, whereas to reduce the air temperature by 2 degrees C only 24 large trees would be required. This study suggests increasing tree canopy cover in the city cannot mitigate UHI adequately but requires choosing the most appropriate tree species to solve this problem. It is imperative to include these types of studies in tree selection and urban development planning to adequately mitigate UHI. PMID- 26828172 TI - Street Orientation and Side of the Street Greatly Influence the Microclimatic Benefits Street Trees Can Provide in Summer. AB - Maintaining human thermal comfort (HTC) is essential for pedestrians because people outside can be more susceptible to heat stress and heat stroke. Modification of street microclimates using tree canopy cover can provide important benefits to pedestrians, but how beneficial and under what circumstances is not clear. On sunny summer days, microclimatic measures were made in residential streets with low and high percentages of tree canopy cover in Melbourne, Australia. Streets with east-west (E-W) and streets with north-south (N-S) orientation were repeatedly measured for air temperature, relative humidity, wind speed, solar radiation, and mean radiant temperature on both sides of the street between early morning and midafternoon. Physiological equivalent temperature was estimated to indicate HTC throughout the day. In streets with high-percentage canopy cover, air temperature, relative humidity, solar radiation, and mean radiant temperature were significantly lower than in streets with low-percentage canopy cover. The reductions in air temperature under high percentage canopy cover were greater for E-W streets (2.1 degrees C) than for N-S streets (0.9 degrees C). For N-S streets, air temperature, mean radiant temperature, and solar radiation were greater on the east pavement in the early morning and greatest on the west pavement in the midafternoon. The midday thermal benefits are restricted to E-W streets, which are oriented in the same direction as the summer sun's zenith. High-percentage canopy cover reduced wind speeds but not enough to offset the other microclimate benefits. These findings can assist urban planners in designing street tree landscapes for optimal HTC in summer, especially in areas of high pedestrian density. PMID- 26828173 TI - Branch Area Index of Solitary Trees: Understanding Its Significance in Regulating Ecosystem Services. AB - The chief aim of this study was to investigate how different species of solitary trees in temperate urban areas vary in their branch structure during winter by assessing branch area indices (BAIs). The BAI data showed significant differences ( < 0.0001) between species and genotypes. The lowest mean BAI in the dataset was for L., which had a BAI of 0.27. L. 'Fastigiata' represented the largest mean BAI of 2.09. The results from the BAI analysis further indicate that within the same species group differences occur between genotypes. For example, the five genotypes of L. range from a mean BAI of 1.77 for 'Globosum' to a mean BAI of 0.50 for 'Fassen Black'. A further aim was to apply the compiled BAI data in the computational modeling program of ENVI-met 3.1, which simulates the surface-air interaction and microclimates in complex urban settings. The simulations focused on mean radiant temperature and wind speed. Results illustrate how wind speed on the leeward side of the trees gradually decrease with an increasing BAI. With an increasing BAI, the Tmrt decreases to the leeward of the row of trees. The results are further discussed in the perspective of sustainable urban development (i.e., where, why, and how the species studied could be integrated in the urban fabric). This is of particular interest for the design of urban green space in densely built-up urban environments where space may be restricted. PMID- 26828174 TI - Surface Water Storage Capacity of Twenty Tree Species in Davis, California. AB - Urban forestry is an important green infrastructure strategy because healthy trees can intercept rainfall, reducing stormwater runoff and pollutant loading. Surface saturation storage capacity, defined as the thin film of water that must wet tree surfaces before flow begins, is the most important variable influencing rainfall interception processes. Surface storage capacity is known to vary widely among tree species, but it is little studied. This research measured surface storage capacities of 20 urban tree species in a rainfall simulator. The measurement system included a rainfall simulator, digital balance, digital camera, and computer. Eight samples were randomly collected from each tree species. Twelve rainfall intensities (3.5-139.5 mm h) were simulated. Leaf-on and leaf-off simulations were conducted for deciduous species. Stem and foliar surface areas were estimated using an image analysis method. Results indicated that surface storage capacities varied threefold among tree species, 0.59 mm for crape myrtle ( L.) and 1.81 mm for blue spruce ( Engelm.). The mean value across all species was 0.86 mm (0.11 mm SD). To illustrate application of the storage values, interception was simulated and compared across species for a 40-yr period with different rainfall intensities and durations. By quantifying the potential for different tree species to intercept rainfall under a variety of meteorological conditions, this study provides new knowledge that is fundamental to validating the cost-effectiveness of urban forestry as a green infrastructure strategy and designing functional plantings. PMID- 26828175 TI - Tree Species Suitability to Bioswales and Impact on the Urban Water Budget. AB - Water movement between soil and the atmosphere is restricted by hardscapes in the urban environment. Some green infrastructure is intended to increase infiltration and storage of water, thus decreasing runoff and discharge of urban stormwater. Bioswales are a critical component of a water-sensitive urban design (or a low impact urban design), and incorporation of trees into these green infrastructural components is believed to be a novel way to return stored water to the atmosphere via transpiration. This research was conducted in The Morton Arboretum's main parking lot, which is one of the first and largest green infrastructure installations in the midwestern United States. The parking lot is constructed of permeable pavers and tree bioswales. Trees in bioswales were evaluated for growth and condition and for their effects on water cycling via transpiration. Our data indicate that trees in bioswales accounted for 46 to 72% of total water outputs via transpiration, thereby reducing runoff and discharge from the parking lot. By evaluating the stomatal conductance, diameter growth, and condition of a variety of tree species in these bioswales, we found that not all species are equally suited for bioswales and that not all are equivalent in their transpiration and growth rates, thereby contributing differentially to the functional capacity of bioswales. We conclude that species with high stomatal conductance and large mature form are likely to contribute best to bioswale function. PMID- 26828176 TI - The Potential Role of Urban Forests in Removing Nutrients from Stormwater. AB - Biofiltration systems can be used to improve the quality of stormwater by treating runoff using plants grown in a moderately permeable soil. Most biofilters use herbaceous species, but in highly urbanized locations, such as streets, trees may be a more suitable vegetation. Biofilters that use urban woody vegetation are less studied. This experiment investigated the use of four street tree species [ Schauer, (R. Br.) Peter G. Wilson & J.T. Waterh., (Sm.) Colvill ex Sweet, and L.] and an unplanted control in model biofilters. All four tree species are used in urban landscapes in southern Australia and were chosen to investigate potential species differences in biofiltration systems. The trees were grown in mesocosms as a randomized block factorial design in soils with three saturated hydraulic conductivity rates (4, 95, and 170 mm h). The trees were regularly flooded with mains water (tap water) or artificial stormwater. Tree growth and nutrient removal performance of the systems were investigated over 13 mo. All four species grew well in all three soils, including one chosen for its low, and potentially growth-limiting, drainage rate. Tree growth increased significantly, except for , when flooded with stormwater. Unplanted controls were a source of nutrients; however, the presence of trees reduced oxidized nitrogen and filterable reactive phosphorus concentrations in leachate. There was little effect of species on the removal of nutrients from stormwater. Trees have the potential to be effective elements in urban biofiltration systems, but further field-level evaluation of these systems is required to fully assess this potential. PMID- 26828177 TI - Soil Carbon and Carbon/Nitrogen Ratio Change under Tree Canopy, Tall Grass, and Turf Grass Areas of Urban Green Space. AB - Soils in urban green spaces are an important carbon (C) store, but urban soils with a high carbon to nitrogen (C/N) ratio can also buffer N eutrophication from fertilizer use or atmospheric deposition. The influence of vegetation management practices on soil C cycling and C/N ratios in urban green spaces is largely unknown. In 2013, we collected replicate ( = 3) soil samples from tree canopy, tall grass, and short turf grass areas ( = 3) at four random plot locations ( = 4) established in 13 golf courses ( = 13). At each sample point, soil was separated into 0- to 0.1-, 0.1- to 0.2-, and 0.2- to 0.3-m depths (total = 1404). Linear mixed models investigated the relationships between soil properties, vegetation attributes, and green space age. Tree canopy soil was less compacted (1.07 g cm) than grassy areas (1.32 g cm). Similarly, tree canopy soil had mean C/N ratios of 17.2, as compared with between 14.2 and 15.3 in grassy areas. Soil properties in tree canopy areas were best explained by tree basal area and understory vegetation volume. Soil C/N increased with increasing understory vegetation, and the difference in soil C/N between tree canopy and short turf grass areas increased over time. The soil properties in tree canopy areas of urban green space mean they can increasingly buffer the localized use of N fertilizers and atmospheric N deposition. Managers of urban green spaces concerned about N pollution of groundwater and waterways could consider planting trees in suitable topographic locations and promoting understory vegetation and surface litter accumulation. PMID- 26828178 TI - Removal of Ozone by Urban and Peri-Urban Forests: Evidence from Laboratory, Field, and Modeling Approaches. AB - A crucial issue in urban environments is the interaction between urban trees and atmospheric pollution, particularly ozone (O). Ozone represents one of the most harmful pollutants in urban and peri-urban environments, especially in warm climates. Besides the large interest in reducing anthropogenic and biogenic precursors of O emissions, there is growing scientific activity aimed at understanding O removal by vegetation, particularly trees. The intent of this paper is to provide the state of the art and suggestions to improve future studies of O fluxes and to discuss implications of O flux studies to maximize environmental services through the planning and management of urban forests. To evaluate and quantify the potential of O removal in urban and peri-urban forests, we describe experimental approaches to measure O fluxes, distinguishing laboratory experiments, field measurements, and model estimates, including recent case studies. We discuss the strengths and weaknesses of the different approaches and conclude that the combination of the three levels of investigation is essential for estimating O removal by urban trees. We also comment on the implications of these findings for planning and management of urban forests, suggesting some key issues that should be considered to maximize O removal by urban and peri-urban forests. PMID- 26828179 TI - Isoprene Emission Factors for Subtropical Street Trees for Regional Air Quality Modeling. AB - Evaluating the environmental benefits and consequences of urban trees supports their sustainable management in cities. Models such as i-Tree Eco enable decision making by quantifying effects associated with particular tree species. Of specific concern are emissions of biogenic volatile organic compounds, particularly isoprene, that contribute to the formation of photochemical smog and ground level ozone. Few studies have quantified these potential disservices of urban trees, and current models predominantly use emissions data from trees that differ from those in our target region of subtropical Australia. The present study aimed (i) to quantify isoprene emission rates of three tree species that together represent 16% of the inventoried street trees in the target region; (ii) to evaluate outputs of the i-Tree Eco model using species-specific versus currently used, generic isoprene emission rates; and (iii) to evaluate the findings in the context of regional air quality. Isoprene emission rates of (Myrtaceae) and (Proteaceae) were 2.61 and 2.06 ug g dry leaf weight h, respectively, whereas (Sapindaceae) was a nonisoprene emitter. We substituted the generic isoprene emission rates with these three empirical values in i-Tree Eco, resulting in a 182 kg yr (97%) reduction in isoprene emissions, totaling 6284 kg yr when extrapolated to the target region. From these results we conclude that care has to be taken when using generic isoprene emission factors for urban tree models. We recommend that emissions be quantified for commonly planted trees, allowing decision-makers to select tree species with the greatest overall benefit for the urban environment. PMID- 26828180 TI - Characterization of Allergen Emission Sources in Urban Areas. AB - Pollen released by urban flora-a major contributor to airborne allergen content during the pollen season-has a considerable adverse impact on human health. Using aerobiological techniques to sample and characterize airborne biological particulate matter (BPM), we can identify the main species contributing to the pollen spectrum and chart variations in counts and overall pollen dynamics throughout the year. However, given the exponential increase in the number of pollen allergy sufferers in built-up areas, new strategies are required to improve the biological quality of urban air. This paper reports on a novel characterization of the potential allergenicity of the tree species most commonly used as ornamentals in Mediterranean cities. Values were assigned to each species based on a number of intrinsic features including pollination strategy, pollen season duration, and allergenic capacity as reported in the specialist literature. Findings were used to generate a database in which groups of conifers, broadleaves, and palm trees were assigned a value of between 0 and 36, enabling their allergenicity to be rated as nil, low, moderate, high, or very high. The case study presented here focuses on the city of Granada in southern Spain. The major airborne-pollen-producing species were identified and the allergenicity of species growing in urban green zones was estimated. Corrective measures are proposed to prevent high allergen levels and thus improve biological air quality. PMID- 26828181 TI - Anthropogenic and Biogenic Features of Long-Term Measured CO Flux in North Downtown Houston, Texas. AB - Long-term urban carbon cycle studies remain rare despite the importance of carbon for energy, air quality, and climate change. To study spatial and temporal variations of energy and carbon fluxes in a subtropical urban environment, eddy covariance flux measurements were conducted north of downtown Houston, TX, using a tall radio-tower installation. The results of the first 2 yr of measurements show that both concentrations and fluxes of CO display typical seasonal and diurnal variations in urban areas. The seasonal variation of net CO flux is driven by steady anthropogenic emissions dominated by car traffic and human respiration, moderated by the local deciduous tree foliage. Weekday-weekend differences were observed in carbon fluxes, but not concentrations, while diurnal changes were dominated by rush-hour peaks from traffic and vegetation influences. Interestingly, CO and CO concentrations, but not CO flux, exhibited long-term declines, especially comparing pre- and post-Hurricane Ike periods. A directional analysis of CO fluxes revealed that the highest fluxes typically occurred from northwest directions, most likely due to emissions from small industrial sources. Car traffic as carbon source was revealed via correlations of CO with CO during the morning rush hours, and of CO flux with traffic counts during winter time. The influence of urban vegetation on net CO fluxes was identified via correlations with daytime photosynthetically active radiation due to photosynthesis, and with nighttime temperatures due to ecosystem respiration. The study site is a net source of CO throughout all seasons. PMID- 26828182 TI - New York Dairy Manure Management Greenhouse Gas Emissions and Mitigation Costs (1992-2022). AB - Livestock manure can be a significant source of greenhouse gases (GHG) including methane (CH) and nitrous oxide (NO). However, GHG emissions are strongly affected by the type of waste management system (WMS) used. For example, CH emissions increase substantially under anaerobic conditions that occur in many WMSs. There is a need for improved estimates at regional and national scales of the effect of WMSs on GHG emissions and identification of opportunities and associated costs to mitigate these emissions. As New York State is the fourth largest dairy producer in the country, our objectives were to quantify (i) the changes in WMS and associated GHG emissions over time, (ii) a methane conversion factor (MCF) derived from existing data from three covered manure storage units in New York, and (iii) the benefit and cost of installing covers and flares to destroy CH from existing storage units. We found that GHG emissions from changing manure management increased from 0.7 Tg carbon dioxide equivalents per year (COe yr) in 1992 to 1.6 Tg COe yr in 2012. We derived an MCF of 0.61 based on data from dairy manure storage units with covers that captured and flared CH in 2010 and used this MCF to project GHG reductions for a statewide mitigation scenario in year 2022. This scenario, covering and flaring CH from 662 manure storage units, mitigates 1.8 Tg COe annually or 62% of manure GHG (CH and NO) at an estimated cost of $224 million ($0.005 L milk or $13 Mg COe). PMID- 26828183 TI - Magnesium Isotope Variations to Trace Liming Input to Terrestrial Ecosystems: A Case Study in the Vosges Mountains. AB - Liming with Ca and Mg carbonates is commonly used to reduce soil and stream acidity and to improve vegetation growth and nutrition in forests. Ten years ago, dolomite lime was experimentally applied to a forest catchment on granite in the Vosges Mountains (northeast France), which is characterized by acid soils and drained by an acid stream. The average Mg isotope composition of the dolomite lime (-1.750/00) was low compared with that of tree foliage (-0.700/00), granite and deep soil layers (-0.400/00), and stream water (-0.800/00) in the control catchment. After liming, the exchangeable Mg concentrations in surface soil layers, which were initially very low, increased, and the Mg isotope composition decreased (up to -0.600/00). The decrease was smaller in deeper layers but not in proportion to the increase in exchangeable Mg content, suggesting contributions from mineralization of organic matter and/or displacement of exchangeable Mg from surface layers. Before application, Mg concentration in beech and fir leaves was low, and that of 1-yr-old fir needles was lower than that in current needles. Internal Mg translocation within fir needles also resulted in a lower deltaMg of older needles. Three years after dolomite application, the Mg isotope composition of plant leaves was lower than that in the control catchment; this decrease (up to -1.000/00) was attributed to direct uptake of Mg from dissolving dolomite. Liming doubled the concentration of Mg in the stream, whereas the Mg isotope composition decreased correspondingly from -0.80 to -1.200/00, indicating a fast transfer of dolomite Mg to the stream. Our findings indicate that monitoring of deltaMg may be a promising tool to study the fate of dolomitic inputs in terrestrial and aquatic ecosystems. PMID- 26828184 TI - Spatial Scale and Field Management Affect Patterns of Phosphorus Loss in Cranberry Floodwaters. AB - Although cranberries ( Ait.) are indigenous to the northeastern United States, phosphorus (P) fertilizer additions and periodic flooding make commercial cranberry a potential source of P to the region's lakes and streams. In this study, we report values of P export in cranberry floodwaters that range from <0.8 to 4.7 kg P ha, generally reflecting differences in the hydrological, edaphic, and management factors underlying soil P transfer to floodwater. The relatively high P loading rate (4.7 P kg P ha) was associated with harvest flooding of organic-rich soils. Periods of winter flooding and the discharge of harvest floodwater from mineral soils resulted in relatively low P loss (<0.8 kg P ha). Increases in concentrations of total dissolved P (DP) and total particulate P (PP) in floodwater as stage decreased below the surface of the cranberry bed were consistent with the transport of dissolved P in soil porewater and mobilization of particulate P in ditches. Variations in floodwater DP, as well as conservative and reactive tracer concentrations, suggested that the processes by which soil P is released to porewater included desorption of near-surface soil P and anaerobic dissolution of iron-P compounds deeper in the soil profile. At the farm scale, concentrations of DP and PP steadily increased over time, presumably because drainage waters from beds farther upgradient had longer contact times with P-rich sources, such as soil porewater and ditch sediments. Overall, the study illustrates the role that scale-dependent processes impart on patterns of P loss in agricultural production systems. PMID- 26828185 TI - Total and Labile Phosphorus Concentrations as Influenced by Riparian Buffer Soil Properties. AB - Riparian buffers can act as a phosphorus (P) source under active stream bank erosion. Using soil and landscape variables (soil series, drainage class, organic matter, and pH) to index P concentrations could improve P loss risk tools for buffers. The objectives of this study were (i) to determine if soil properties could predict total and labile P concentrations within a 10-ha riparian buffer and (ii) to quantify the degree of spatial dependence of P and related properties. Soil samples were taken in 15-cm increments to a depth of 60 cm using a grid ( = 71) from an established riparian buffer along the Rock River in Vermont. Total soil P (TP), plant-available P determined by Modified Morgan extraction (MM-P), pH, soil organic matter (SOM), soil texture, and select cations were measured. We found that TP (152-1536 mg P kg) and MM-P (0.4-14.6 mg kg) ranged widely, with distinct differences between soil series. Mean TP and MM P were greater in alluvial and glaciolacustrine soils compared with glacial till. Across all samples, MM-P was weakly related to soil properties; however, total labile P (orthophosphate + organic P measured by ICP) and unreactive labile P (ICP-P - colorimetric-P) could both be predicted by SOM ( = 0.59 and 0.73, respectively). Strong spatial dependence was found for P and related properties as revealed by geospatial analyses. Results show that P availability in the buffer was strongly related to soil genesis and support site-specific approaches for P loss risk evaluation in buffers. PMID- 26828186 TI - Lagdo Dam Flood Disaster of 2012: An Assessment of the Concentrations, Sources, and Risks of PAHs in Floodplain Soils of the Lower Reaches of River Niger, Nigeria. AB - The concentrations of the USEPA 16 priority polycyclic aromatic hydrocarbons (PAHs) in soils of the floodplain of the lower reaches of River Niger, Nigeria, were investigated following the Lagdo Dam flood disaster of 2012. The aim was to provide information on the extent of contamination, sources, and risks of PAHs in these soils. The concentrations of Sigma16 PAHs in the floodplain soils ranged from 812 to 10,700 MUg kg. The benzo(a)pyrene (BaP) toxic equivalence and incremental lifetime cancer risk (ILCR) factors were used to evaluate the risk of human exposure to PAHs in these soils. The concentrations of benzo(a)pyrene carcinogenic equivalence (BaP) and benzo(a)pyrene mutagenic equivalence (BaP) ranged from not detected to 4090 MUg kg and not detected to 4150 MUg kg, respectively. The total ILCR for children and adults was calculated as the summation of the individual risks through the three routes of exposure, (ingestion, dermal, and inhalation of vapor or dust). The values obtained indicate that there are 6450 and 4480 chances in one million equally exposed persons to develop the risk of cancer for children and adults, respectively, which were higher than the USEPA acceptable guideline value of one cancer case in one million (10) equally exposed persons. The PAHs source evaluation, using the diagnostic ratios and principal component analysis (PCA), indicated that the major sources of PAHs in these soils were fossil fuel combustion, gas flaring, wood combustion, traffic emissions, and input from petroleum. PMID- 26828187 TI - Fecal Sterol and Runoff Analysis for Nonpoint Source Tracking. AB - Fecal pollution source identification is needed to quantify risk, target installation of source controls, and assess performance of best management practices in impaired surface waters. Sterol analysis is a chemical method for fecal source tracking that allows for differentiation between several fecal pollution sources. The objectives of this study were to use these chemical tracers for quantifying human fecal inputs in a mixed-land-use watershed without point sources of pollution and to determine the relationship between land use and sterol ratios. Fecal sterol analysis was performed on bed and suspended sediment from impaired streams. Human fecal signatures were found at sites with sewer overflow and septic inputs. Different sterol ratios used to indicate human fecal pollution varied in their sensitivity. Next, geospatial data was used to determine the runoff volumes associated with each land-use category in the watersheds. Fecal sterol ratios were compared between sampling locations and correlations were tested between ratio values and percentage of runoff for a given land-use category. Correlation was not observed between percentage of runoff from developed land and any of the five tested human-indicating sterol ratios in streambed sediments, confirming that human fecal inputs were not evenly distributed across the urban landscape. Several practical considerations for adopting this chemical method for microbial source tracking in small watersheds are discussed. Results indicate that sterol analysis is useful for identifying the location of human fecal nonpoint-source inputs. PMID- 26828188 TI - Urea Fertilizer and pH Influence on Sorption Process of Flumetsulam and MCPA Acidic Herbicides in a Volcanic Soil. AB - The aim of this study was to evaluate the influence of urea fertilizer and pH on the sorption process of two acidic herbicides, flumetsulam (2',6'-difluoro-5 methyl[1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonanilide) and MCPA (4-chloro- tolyloxyacetic acid), on an Andisol. Urea reduced the adsorption of MCPA but not that of flumetsulam. The Freundlich parameter of MCPA decreased from 8.5 to 5.1 mg L kg. This finding could be attributed to an increase in dissolved organic C due to an initial increase in soil pH for urea application. The higher acidic character of MCPA compared with that of flumetsulam produced a greater hydrolysis of urea, leading to a further pH increase. A marked effect of pH on the adsorption of both herbicides was observed. The organic C distribution coefficient () values for flumetsulam were in the range of 74 to 10 L kg, while those of MCPA were in the range of 208 to 45 L kg. In the kinetic studies, the pseudo-second-order model appeared to fit the data best ( > 0.994). The initial adsorption rates () ranged from 20.00 to 4.59 mg kg h for flumetsulam and from 125.00 to 25.60 mg kg hfor MCPA. Both herbicides were adsorbed rapidly during the first stage of the sorption process, and the rates of sorption were dependent on pH. The application of the Elovich and Weber-Morris models led us to conclude that mass transfer through the boundary layer and, to a lesser degree, intraparticle diffusion were influenced by the chemical character of the herbicide. These results suggest that urea application could increase leaching of acid herbicides in soils. PMID- 26828189 TI - Electron Donor Substances and Iron Oxides Stimulate Anaerobic Dechlorination of DDT in a Slurry System with Hydragric Acrisols. AB - The interactive effects between electron donor substances and iron (Fe) oxides have significant influence on electron transfer and the growth of Fe-reducing bacteria, which may affect the reductive dechlorination of 1,1,1-trichoro-2,2 bis(p-chlorophenyl)ethane (DDT) in soils. To evaluate the roles of volatile fatty acids and Fe(III) oxide in accelerating the reductive dechlorination of DDT in Hydragric Acrisols, a batch anaerobic incubation experiment was conducted in a slurry system with the following seven treatments: sterile soil, control (DDT contaminated soil), lactic acid, propionic acid, goethite, lactic acid + goethite, and propionic acid + goethite. Results showed that after 20 d of incubation, DDT residues for these treatments decreased by 34, 65, 77, 81, 77, 90, and 92% of the initial quantities, respectively, with 1,1-dichloro-2,2-bis(4 chlorophenyl)-ethane as the dominant metabolite. The application of lactic acid had no significant effect on DDT dechlorination in the first 8 d while the methanogenesis rate increased quickly but accelerated DDT dechlorination after Day 8 while the methanogenesis rate decreased and Fe(II) contents increased. The application of propionic acid enhanced DDT dechlorination rates throughout the incubation. The amendment by goethite stimulated microbial reduction of Fe(III) oxides to generate Fe(II), which was an efficient electron donor, thus accelerating DDT dechlorination significantly in the early incubation period. A synergetic interaction that accelerated DDT dechlorination, either between lactic acid and goethite or between propionic acid and goethite, was obtained. The results will be of great significance to develop efficient in situ remediation technology of DDT-contaminated soil. PMID- 26828190 TI - Chloride Sources and Losses in Two Tile-Drained Agricultural Watersheds. AB - Chloride is a relatively unreactive plant nutrient that has long been used as a biogeochemical tracer but also can be a pollutant causing aquatic biology impacts when concentrations are high, typically from rock salt applications used for deicing roads. Chloride inputs to watersheds are most often from atmospheric deposition, road salt, or agricultural fertilizer, although studies on agricultural watersheds with large fertilizer inputs are few. We used long-term (21 and 17 yr) chloride water quality data in two rivers of east-central Illinois to better understand chloride biogeochemistry in two agricultural watersheds (Embarras and Kaskaskia), the former with a larger urban land use and both with extensive tile drainage. During our sampling period, the average chloride concentration was 23.7 and 20.9 mg L in the Embarras and Kaskaskia Rivers, respectively. Annual fluxes of chloride were 72.5 and 61.2 kg ha yr in the Embarras and Kaskaskia watersheds, respectively. In both watersheds, fertilizer chloride was the dominant input (~49 kg ha yr), with road salt likely the other major source (23.2 and 7.2 kg ha yr for the Embarras and Kaskaskia watersheds, respectively). Combining our monitoring data with earlier published data on the Embarras River showed an increase in chloride concentrations as potash use increased in Illinois during the 1960s and 1970s with a lag of about 2 to 6 yr to changes in potash inputs based on a multiple-regression model. In these agricultural watersheds, riverine chloride responds relatively quickly to potash fertilization as a result of tile-drainage. PMID- 26828191 TI - Urea Hydrolysis Rate in Soil Toposequences as Influenced by pH, Carbon, Nitrogen, and Soluble Metals. AB - A simultaneous increase in the use of urea fertilizer and the incidence of harmful algal blooms worldwide has generated interest in potential loss pathways of urea from agricultural areas. The objective of this research was to study the rate of urea hydrolysis in soil profile toposequences sampled from the Coastal Plain (CP) and Piedmont (PM) regions of Maryland to understand native urea hydrolysis rates (UHRs) as well as the controls governing urea hydrolysis both across a landscape and with depth in the soil profile. A pH-adjustment experiment was conducted to explore the relationship between pH and urea hydrolysis because of the importance of pH to both agronomic productivity and microbial communities. Soils were sampled from both A and B horizons along transects containing an agricultural field (AG), a grassed field border (GB), and a perennially vegetated zone adjacent to surface water. On average, the A-horizon UHRs were eight times greater than corresponding B-horizon rates, and within the CP, the riparian zone (RZ) soils hydrolyzed urea faster than the agricultural soils. The pH adjustment of these soils indicated the importance of organic-matter-related factors (C, N, extractable metals) in determining UHR. These results suggest that organic-matter rich RZ soils may be valuable in mitigating losses of urea from neighboring fields. Additional field-scale urea hydrolysis studies would be valuable to corroborate the mechanisms described herein and to explore the conditions affecting the fate and transport of urea in agroecosystems. PMID- 26828192 TI - Effect of Pine Waste and Pine Biochar on Nitrogen Mobility in Biosolids. AB - Humanity produces ~27 kg of dry matter in biosolids per person per year. Land application of biosolids can improve crop production and remediate soils but may result in excessive nitrate N (NO-N) leaching. Carbonaceous materials can reduce the environmental impact of biosolids application. We aimed to ascertain and compare the potentials for Monterey pine ( D. Don)-sawdust-derived biochars and raw sawdust to reduce NO-N leaching from biosolids. We used batch sorption experiments 1:10 ratio of material to solution (100 mg kg of NH or NO) and column leaching experiments with columns containing biosolids (2.7% total N, 130 mg kg NH and 1350 mg kg NO) mixed with soil, biochar, or sawdust. One type of low temperature (350 degrees C) biochar sorbed 335 mg kg NH, while the other biochars and sawdust sorbed <200 mg kg NH. None of the materials sorbed NO. Biochar added at rates of 20 to 50% reduced NH-N (<1% of total N) leaching from columns by 40 to 80%. Nitrate leaching (<7% of total N) varied little with biochar form or rate but was reduced by sawdust. Incorporating dried sawdust with biosolids showed promise for mitigating NO-N leaching. This effect likely is due to sorption into the pores of the biochar combined with denitrification and immobilization of N rather than chemical sorption onto surfaces. PMID- 26828193 TI - Wetland Soil Carbon in a Watershed Context for the Prairie Pothole Region. AB - Wetland restoration in the Prairie Pothole Region (PPR) often involves soil removal to enhance water storage volume and/or remove seedbanks of invasive species. Consequences of soil removal could include loss of soil organic carbon (SOC), which is important to ecosystem functions such as water-holding capacity and nutrient retention needed for plant re-establishment. We used watershed position and surface flow pathways to classify wetlands into headwater or network systems to address two questions relevant to carbon (C) cycling and wetland restoration practices: (i) Do SOC stocks and C mineralization rates vary with landscape position in the watershed (headwater vs. network systems) and land use (restored vs. native prairie grasslands)? (ii) How might soil removal affect plant emergence? We addressed these questions using wetlands at three large (?200 ha) study areas in the central North Dakota PPR. We found the cumulative amount of C mineralization over 90 d was 100% greater for network than headwater systems, but SOC stocks were similar, suggesting greater C inputs beneath wetlands connected by higher-order drainage lines are balanced by greater rates of C turnover. Land use significantly affected SOC, with greater stocks beneath native prairie than restored grasslands for both watershed positions. Removal of mineral soil negatively affected plant emergence. This watershed-based framework can be applied to guide restoration designs by (i) weighting wetlands based on surface flow connectivity and contributing area and (ii) mapping the effects of soil removal on plant and soil properties for network and headwater wetland systems in the PPR. PMID- 26828194 TI - First microbial encounters. PMID- 26828196 TI - Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. AB - Exposure of newborns to the maternal vaginal microbiota is interrupted with cesarean birthing. Babies delivered by cesarean section (C-section) acquire a microbiota that differs from that of vaginally delivered infants, and C-section delivery has been associated with increased risk for immune and metabolic disorders. Here we conducted a pilot study in which infants delivered by C section were exposed to maternal vaginal fluids at birth. Similarly to vaginally delivered babies, the gut, oral and skin bacterial communities of these newborns during the first 30 d of life was enriched in vaginal bacteria--which were underrepresented in unexposed C-section-delivered infants--and the microbiome similarity to those of vaginally delivered infants was greater in oral and skin samples than in anal samples. Although the long-term health consequences of restoring the microbiota of C-section-delivered infants remain unclear, our results demonstrate that vaginal microbes can be partially restored at birth in C section-delivered babies. PMID- 26828197 TI - Clinical outcomes in patients with T4 laryngeal cancer treated with primary radiotherapy versus primary laryngectomy. AB - BACKGROUND: The purpose of this study was to determine the clinical outcomes of T4 laryngeal cancers. METHODS: T4 laryngeal cancers treated with curative intent from January 2003 to December 2010 were analyzed. Outcomes were evaluated in both primary radiotherapy (+/- chemotherapy) (RT/CRT) and primary surgery cohorts. RESULTS: Among the 65 primary RT/CRT and 42 primary surgery patients included, median follow-up was 4.4 years. There was a trend for improved locoregional control with surgery (74% vs 88%; p = .08). In the RT/CRT group the 3-year laryngectomy-free survival was 67%. The 2-year gastrostomy dependency rate was 23% with RT/CRT versus 6% with primary surgery (p = .07). Overall survival (OS) at 3 years was significantly lower in the RT/CRT versus primary surgery group (41% vs 70%; p < .01). CONCLUSION: Laryngeal preservation is achieved in over two thirds of patients with primary RT/CRT. Patients with low volume minimal cartilage involvement T4 disease may be best suited to RT/CRT. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2035-E2040, 2016. PMID- 26828195 TI - Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition. AB - Although mechanisms of acquired resistance of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here we observe that acquired resistance caused by the EGFR(T790M) gatekeeper mutation can occur either by selection of pre-existing EGFR(T790M) positive clones or via genetic evolution of initially EGFR(T790M)-negative drug tolerant cells. The path to resistance impacts the biology of the resistant clone, as those that evolved from drug-tolerant cells had a diminished apoptotic response to third-generation EGFR inhibitors that target EGFR(T790M); treatment with navitoclax, an inhibitor of the anti-apoptotic factors BCL-xL and BCL-2 restored sensitivity. We corroborated these findings using cultures derived directly from EGFR inhibitor-resistant patient tumors. These findings provide evidence that clinically relevant drug-resistant cancer cells can both pre-exist and evolve from drug-tolerant cells, and they point to therapeutic opportunities to prevent or overcome resistance in the clinic. PMID- 26828198 TI - Pure electrical, highly-efficient and sidelobe free coherent Raman spectroscopy using acousto-optics tunable filter (AOTF). AB - Fast and sensitive Raman spectroscopy measurements are imperative for a large number of applications in biomedical imaging, remote sensing and material characterization. Stimulated Raman spectroscopy offers a substantial improvement in the signal-to-noise ratio but is often limited to a discrete number of wavelengths. In this report, by introducing an electronically-tunable acousto optical filter as a wavelength selector, a novel approach to a broadband stimulated Raman spectroscopy is demonstrated. The corresponding Raman shift covers the spectral range from 600 cm(-1) to 4500 cm(-1), sufficient for probing most vibrational Raman transitions. We validated the use of the new instrumentation to both coherent anti-Stokes scattering (CARS) and stimulated Raman scattering (SRS) spectroscopies. PMID- 26828199 TI - Pharmacological treatment for Buerger's disease. AB - BACKGROUND: Buerger's disease (thromboangiitis obliterans) is a non atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain. OBJECTIVES: To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease. SEARCH METHODS: The Cochrane Vascular Trials Search Co-ordinator searched their Specialised Register (last searched in April 2015) and the Cochrane Register of Studies (Issue 3, 2015). The review authors searched trial registers and the European grey literature; screened reference lists of relevant studies, and contacted study authors and major pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease. DATA COLLECTION AND ANALYSIS: Two review authors, independently assessed the studies, extracted data and performed data analysis. MAIN RESULTS: Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid.Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; one study; moderate quality evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; one study; moderate quality evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; one study; moderate quality evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; two studies; I2 = 0%; very low quality evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; one study; low quality evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; one study; moderate quality evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; one study; moderate quality evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; one study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; one study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low quality evidence).Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study.Overall, the quality of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information regarding for example baseline tobacco exposure. AUTHORS' CONCLUSIONS: Moderate quality evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Verylow and low quality evidence suggests there is no difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very-low quality evidence suggests there is no difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. High quality trials assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed. PMID- 26828200 TI - South to south learning in great ape conservation. AB - Despite evidence that killing of Bornean Orangutan (Pongo pygmaeus) in South-East Asia is a major threat to the species, few researchers and non-governmental conservationists have addressed it in management and research, and there is virtually no implementation of anti-killing strategies. In large parts of the Congo Basin, Central Africa, instead, illegal killing of great apes is acknowledged to be their largest threat, and many conservation strategies have been used to reduce killing pressure. However, since these strategies have not been subject to systematic and comprehensive review, it remains unclear which of them have been successful and why. Knowledge of the success, failure, and practices of common conservation strategies to manage great ape killing is critical to ensure adaptive conservation management in the Congo Basin. Understanding the Congo context also facilitates simultaneously highlighting great ape killing in Borneo and suggesting solutions to manage orangutan killing. Here, we compile and analyze the available literature on great ape conservation strategies for reducing killing rates in the Congo Basin. Through a systematic literature review of 198 publications, we find that the most widely employed conservation strategies in the Congo Basin are legislation and law enforcement, protected area management, community-based conservation, alternatives to bushmeat consumption and trade, ecotourism, education, and capacity building. Despite lack of rigorous post-intervention evaluation of conservation impact, we derive several recommendations for addressing the orangutan killing issue in Borneo. A critical lesson, widely applicable to developing countries for conservationists and not limited to Congo Basin realities, is the need for rigorous post intervention evaluations compared to pre-intervention baselines and over appropriate time frames. Am. J. Primatol. 78:669-678, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26828201 TI - Expression of mRNA Encoding Mcu and Other Mitochondrial Calcium Regulatory Genes Depends on Cell Type, Neuronal Subtype, and Ca2+ Signaling. AB - Uptake of Ca2+ into the mitochondrial matrix controls cellular metabolism and survival-death pathways. Several genes are implicated in controlling mitochondrial Ca2+ uptake (mitochondrial calcium regulatory genes, MCRGs), however, less is known about the factors which influence their expression level. Here we have compared MCRG mRNA expression, in neural cells of differing type (cortical neurons vs. astrocytes), differing neuronal subtype (CA3 vs. CA1 hippocampus) and in response to Ca2+ influx, using a combination of qPCR and RNA seq analysis. Of note, we find that the Mcu-regulating Micu gene family profile differs substantially between neurons and astrocytes, while expression of Mcu itself is markedly different between CA3 and CA1 regions in the adult hippocampus. Moreover, dynamic control of MCRG mRNA expression in response to membrane depolarization-induced Ca2+ influx is also apparent, resulting in repression of Letm1, as well as Mcu. Thus, the mRNA expression profile of MCRGs is not fixed, which may cause differences in the coupling between cytoplasmic and mitochondrial Ca2+, as well as diversity of mitochondrial Ca2+ uptake mechanisms. PMID- 26828202 TI - A Conserved HIV-1-Derived Peptide Presented by HLA-E Renders Infected T-cells Highly Susceptible to Attack by NKG2A/CD94-Bearing Natural Killer Cells. AB - Major histocompatibility class I (MHC-I)-specific inhibitory receptors on natural killer (NK) cells (iNKRs) tolerize mature NK cell responses toward normal cells. NK cells generate cytolytic responses to virus-infected or malignant target cells with altered or decreased MHC-I surface expression due to the loss of tolerizing ligands. The NKG2A/CD94 iNKR suppresses NK cell responses through recognition of the non-classical MHC-I, HLA-E. We used HIV-infected primary T-cells as targets in an in vitro cytolytic assay with autologous NK cells from healthy donors. In these experiments, primary NKG2A/CD94(+) NK cells surprisingly generated the most efficient responses toward HIV-infected T-cells, despite high HLA-E expression on the infected targets. Since certain MHC-I-presented peptides can alter recognition by iNKRs, we hypothesized that HIV-1-derived peptides presented by HLA-E on infected cells may block engagement with NKG2A/CD94, thereby engendering susceptibility to NKG2A/CD94(+) NK cells. We demonstrate that HLA-E is capable of presenting a highly conserved peptide from HIV-1 capsid (AISPRTLNA) that is not recognized by NKG2A/CD94. We further confirmed that HLA-C expressed on HIV infected cells restricts attack by KIR2DL(+) CD56(dim) NK cells, in contrast to the efficient responses by CD56(bright) NK cells, which express predominantly NKG2A/CD94 and lack KIR2DLs. These findings are important since the use of NK cells was recently proposed to treat latently HIV-1-infected patients in combination with latency reversing agents. Our results provide a mechanistic basis to guide these future clinical studies, suggesting that ex vivo-expanded NKG2A/CD94(+) KIR2DL(-) NK cells may be uniquely beneficial. PMID- 26828204 TI - Validation of Cis and Trans Modes in Multistep Phosphotransfer Signaling of Bacterial Tripartite Sensor Kinases by Using Phos-Tag SDS-PAGE. AB - Tripartite sensor kinases (TSKs) have three phosphorylation sites on His, Asp, and His residues, which are conserved in a histidine kinase (HK) domain, a receiver domain, and a histidine-containing phosphotransmitter (HPt) domain, respectively. By means of a three-step phosphorelay, TSKs convey a phosphoryl group from the gamma-phosphate group of ATP to the first His residue in the HK domain, then to the Asp residue in the receiver domain, and finally to the second His residue in the HPt domain. Although TSKs generally form homodimers, it was unknown whether the mode of phosphorylation in each step was intramolecular (cis) or intermolecular (trans). To examine this mode, we performed in vitro complementation analyses using Ala-substituted mutants of the ATP-binding region and three phosphorylation sites of recombinant ArcB, EvgS, and BarA TSKs derived from Escherichia coli. Phosphorylation profiles of these kinases, determined by using Phos-tag SDS-PAGE, showed that the sequential modes of the three-step phosphoryl-transfer reactions of ArcB, EvgS, and BarA are all different: cis trans-trans, cis-cis-cis, and trans-trans-trans, respectively. The inclusion of a trans mode is consistent with the need to form a homodimer; the fact that all the steps for EvgS have cis modes is particularly interesting. Phos-tag SDS-PAGE therefore provides a simple method for identifying the unique and specific phosphotransfer mode for a given kinase, without taking complicated intracellular elements into consideration. PMID- 26828203 TI - The Emotional Gatekeeper: A Computational Model of Attentional Selection and Suppression through the Pathway from the Amygdala to the Inhibitory Thalamic Reticular Nucleus. AB - In a complex environment that contains both opportunities and threats, it is important for an organism to flexibly direct attention based on current events and prior plans. The amygdala, the hub of the brain's emotional system, is involved in forming and signaling affective associations between stimuli and their consequences. The inhibitory thalamic reticular nucleus (TRN) is a hub of the attentional system that gates thalamo-cortical signaling. In the primate brain, a recently discovered pathway from the amygdala sends robust projections to TRN. Here we used computational modeling to demonstrate how the amygdala-TRN pathway, embedded in a wider neural circuit, can mediate selective attention guided by emotions. Our Emotional Gatekeeper model demonstrates how this circuit enables focused top-down, and flexible bottom-up, allocation of attention. The model suggests that the amygdala-TRN projection can serve as a unique mechanism for emotion-guided selection of signals sent to cortex for further processing. This inhibitory selection mechanism can mediate a powerful affective 'framing' effect that may lead to biased decision-making in highly charged emotional situations. The model also supports the idea that the amygdala can serve as a relevance detection system. Further, the model demonstrates how abnormal top-down drive and dysregulated local inhibition in the amygdala and in the cortex can contribute to the attentional symptoms that accompany several neuropsychiatric disorders. PMID- 26828205 TI - Correction: Buruli Ulcer in Cameroon: The Development and Impact of the National Control Programme. PMID- 26828206 TI - A Retrospective Analysis of the Impact of Myomectomy on Survival in Uterine Sarcoma. AB - Laparoscopic myomectomy is a minimally invasive, conservative surgical approach commonly used for the treatment of uterine fibroids. However, there is a lack of effective means to distinguish the nature of uterine tumors prior to surgery. The impact of fibroid morcellation during laparoscopic surgery on the dissemination of cancerous uterine fibroids and long-term survival of patients has gained increasing attention. A retrospective cohort study was conducted to analyze the impact of different surgical approaches on recurrence-free survival (RFS) and overall survival (OS) in patients with a postoperative pathological diagnosis of uterine sarcoma at a single medical center. Patients who underwent the first surgery for uterine fibroids (confined to the uterus) and had a postoperative pathological diagnosis of uterine sarcoma were selected in the Chinese PLA General Hospital from January 2005 to January 2014. Based on the use of fibroid morcellation, the subjects were divided into fibroid morcellation (FM) and total hysterectomy (TH, non-morcellation) groups. Follow-up outcomes, including RFS and OS times, were observed. In total, 59 patients were included, with 30 cases in the FM group and 29 cases in the TH group. There were no significant differences in RFS and OS time between the two groups (RFS: P = 0.16, OS: P = 0.09). Multivariate correlation analysis showed that the impact of a higher grade level on RFS and OS was nearly 2-fold the impact of a lower grade level (RFS: P = 0.04, odds ratio (OR) = 1.97; OS: P = 0.03, OR = 2.29). Intraoperative morcellation, postoperative adjuvant therapy, age, tumor size, FIGO stage, and surgical approach were not risk factors affecting RFS and OS. Fibroid morcellation during laparoscopic surgery (including laparoscopic, transvaginal and transabdominal approaches) had no significant impact on RFS and OS time in patients. However, the 5-year RFS and OS rates were both lower in the FM group than in the TH group. Grade level was a significant risk factor for the prognosis of patients with uterine sarcoma. PMID- 26828207 TI - The Posterior Limb of the Internal Capsule as the Subcortical Transitional Zone of the Anterior and Posterior Circulations: Insights from Human 7T MRI. AB - BACKGROUND: In patients with cerebral infarction, identifying the distribution of infarction and the relevant artery is essential for ascertaining the underlying vascular pathophysiological mechanisms and preventing subsequent stroke. However, visualization of the basal perforating arteries (BPAs) has had limited success, and simultaneous viewing of background anatomical structures has only rarely been attempted in living human brains. Our study aimed at identifying the BPAs with 7T MRI and evaluating their distribution in the subcortical structures, thereby showing the clinical significance of the technique. METHODS: Twenty healthy subjects and 1 patient with cerebral infarction involving the posterior limb of the internal capsule (ICpost) and thalamus underwent 3-dimensional fast spoiled gradient-echo sequence as time-of-flight magnetic resonance angiography (MRA) at 7T with a submillimeter resolution. The MRA was modified to detect inflow signals from BPAs, while preserving the background anatomical signals. BPA stems and branches in the subcortical structures and their origins were identified on images, using partial maximum intensity projection in 3 dimensions. RESULTS: A branch of the left posterior cerebral artery (PCA) in the patient ran through both the infarcted thalamus and ICpost and was clearly the relevant artery. In 40 intact hemispheres in healthy subjects, 571 stems and 1,421 branches of BPAs were detected in the subcortical structures. No significant differences in the numbers of stems and branches were observed between the intact hemispheres. The numbers deviated even less across subjects. The distribution analysis showed that the subcortical structures of the telencephalon, such as the caudate nucleus, anterior limb of the internal capsule, and lenticular nucleus, were predominantly supplied by BPAs from the anterior circulation. In contrast, the thalamus, belonging to the diencephalon, was mostly fed by BPAs from the posterior circulation. However, compared with other subcortical structures, the ICpost, which marks the anatomical boundary between the telencephalon and the diencephalon, was supplied by BPAs with significantly more diverse origins. These BPAs originated from the internal carotid artery (23.1%), middle cerebral artery (38.5%), PCA (17.3%), and the posterior communicating artery (21.1%). CONCLUSIONS: The modified MRI method allowed the detection of the relevant BPA within the infarcted area in the stroke survivor as well as the BPAs in the subcortical structures of living human brains. Based on in vivo BPA distribution analyses, the ICpost is the transitional zone of the anterior and posterior cerebral circulations. PMID- 26828208 TI - Activation of Dll4/Notch Signaling and Hypoxia-Inducible Factor-1 Alpha Facilitates Lymphangiogenesis in Lacrimal Glands in Dry Eye. AB - PURPOSE: By using hypoxia-inducible factor-1 alpha conditional knockout (HIF 1alpha CKO) mice and a dry eye (DE) mouse model, we aimed to determine the role played by delta-like ligand 4 (Dll4)/Notch signaling and HIF-1alpha in the lymphangiogenesis of lacrimal glands (LGs). METHODS: C57BL/6 mice were housed in a controlled-environment chamber for DE induction. During DE induction, the expression level of Dll4/Notch signaling and lymphangiogenesis in LGs was measured by quantitative RT-PCR, immunoblot, and immunofluorescence staining. Next, lymphangiogenesis was measured after Dll4/Notch signal inhibition by anti Dll4 antibody or gamma-secretase inhibitor. Using HIF-1alpha CKO mice, the expression of Dll4/Notch signaling and lymphangiogenesis in LGs of DE-induced HIF 1alpha CKO mice were assessed. Additionally, the infiltration of CD45+ cells in LGs was assessed by immunohistochemical (IHC) staining and flow cytometry for each condition. RESULTS: DE significantly upregulated Dll4/Notch and lymphangiogenesis in LGs. Inhibition of Dll4/Notch significantly suppressed lymphangiogenesis in LGs. Compared to wild-type (WT) mice, DE induced HIF-1alpha CKO mice showed markedly low levels of Dll4/Notch and lymphangiogenesis. Inhibition of lymphangiogenesis by Dll4/Notch suppression resulted in increased CD45+ cell infiltration in LGs. Likewise, CD45+ cells infiltrated more in the LGs of HIF-1alpha CKO DE mice than in non-DE HIF-1alpha CKO mice. CONCLUSIONS: Dll4/Notch signaling and HIF-1alpha are closely related to lymphangiogenesis in DE-induced LGs. Lymphangiogenesis stimulated by Dll4/Notch and HIF-1alpha may play a role in protecting LGs from DE-induced inflammation by aiding the clearance of immune cells from LGs. PMID- 26828210 TI - Missions of Journal of Movement Disorders. PMID- 26828209 TI - Detrended Fluctuation Analysis of Heart Rate Dynamics Is an Important Prognostic Factor in Patients with End-Stage Renal Disease Receiving Peritoneal Dialysis. AB - BACKGROUND AND OBJECTIVES: Patients with severe kidney function impairment often have autonomic dysfunction, which could be evaluated noninvasively by heart rate variability (HRV) analysis. Nonlinear HRV parameters such as detrended fluctuation analysis (DFA) has been demonstrated to be an important outcome predictor in patients with cardiovascular diseases. Whether cardiac autonomic dysfunction measured by DFA is also a useful prognostic factor in patients with end-stage renal disease (ESRD) receiving peritoneal dialysis (PD) remains unclear. The purpose of the present study was designed to test the hypothesis. MATERIALS AND METHODS: Patients with ESRD receiving PD were included for the study. Twenty-four hour Holter monitor was obtained from each patient together with other important traditional prognostic makers such as underlying diseases, left ventricular ejection fraction (LVEF) and serum biochemistry profiles. Short term (DFAalpha1) and long-term (DFAalpha2) DFA as well as other linear HRV parameters were calculated. RESULTS: A total of 132 patients (62 men, 72 women) with a mean age of 53.7+/-12.5 years were recruited from July 2007 to March 2009. During a median follow-up period of around 34 months, eight cardiac and six non cardiac deaths were observed. Competing risk analysis demonstrated that decreased DFAalpha1 was a strong prognostic predictor for increased cardiac and total mortality. ROC analysis showed that the AUC of DFAalpha1 (<0.95) to predict mortality was 0.761 (95% confidence interval (CI). = 0.617-0.905). DFAalpha1? 0.95 was associated with lower cardiac mortality (Hazard ratio (HR) 0.062, 95% CI = 0.007-0.571, P = 0.014) and total mortality (HR = 0.109, 95% CI = 0.033-0.362, P = 0.0003). CONCLUSION: Cardiac autonomic dysfunction evaluated by DFAalpha1 is an independent predictor for cardiac and total mortality in patients with ESRD receiving PD. PMID- 26828211 TI - Clinical Approach to Progressive Supranuclear Palsy. AB - Sixty years ago, Steele, Richardson and Olszewski designated progressive supranuclear palsy (PSP) as a new clinicopathological entity in their seminal paper. Since then, in addition to the classic Richardson's syndrome (RS), different clinical phenotypic presentations have been linked with this four repeat tauopathy. The clinical heterogeneity is associated with variability of regional distribution and severity of abnormal tau accumulation and neuronal loss. In PSP subtypes, the presence of certain clinical pointers may be useful for antemortem prediction of the underlying PSP-tau pathology. Midbrain atrophy on conventional MRI correlates with the clinical phenotype of RS but is not predictive of PSP pathology. Cerebrospinal fluid biomarkers and tau ligand positron emission tomography are promising biomarkers of PSP. A multidisciplinary approach to meet the patients' complex needs is the current core treatment strategy for this devastating disorder. PMID- 26828212 TI - Mechanism of Anti-alpha-Synuclein Immunotherapy. AB - Immunization therapy targeting alpha-synuclein has emerged as a promising approach for Parkinson's disease and perhaps for other synucleinopathies. Several antibodies have shown therapeutic effects in mouse models of synucleinopathies and have alleviated the pathological and behavioral phenotypes of these mice. The mechanisms through which the immunization therapy works were initially puzzling, especially given that alpha-synuclein is a typical cytosolic protein. Recent studies, however, suggested that extracellular alpha-synuclein is an important pathogenic entity, and hence, a target for immunotherapy. Here, we review the literature describing immunization therapy for synucleinopathies in mouse models and provide current thoughts on the potential mechanisms underlying the therapeutic effects of alpha-synuclein immunotherapy. PMID- 26828213 TI - Clinical Heterogeneity of Atypical Pantothenate Kinase-Associated Neurodegeneration in Koreans. AB - OBJECTIVE: Neurodegeneration with brain iron accumulation (NBIA) represents a group of inherited movement disorders characterized by iron accumulation in the basal ganglia. Recent advances have included the identification of new causative genes and highlighted the wide phenotypic variation between and within the specific NBIA subtypes. This study aimed to investigate the current status of NBIA in Korea. METHODS: We collected genetically confirmed NBIA patients from twelve nationwide referral hospitals and from a review of the literature. We conducted a study to describe the phenotypic and genotypic characteristics of Korean adults with atypical pantothenate kinase-associated neurodegeneration (PKAN). RESULTS: Four subtypes of NBIA including PKAN (n = 30), PLA2G6-related neurodegeneration (n = 2), beta-propeller protein-associated neurodegeneration (n = 1), and aceruloplasminemia (n = 1) have been identified in the Korean population. The clinical features of fifteen adults with atypical PKAN included early focal limb dystonia, parkinsonism-predominant feature, oromandibular dystonia, and isolated freezing of gait (FOG). Patients with a higher age of onset tended to present with parkinsonism and FOG. The p.R440P and p.D378G mutations are two major mutations that represent approximately 50% of the mutated alleles. Although there were no specific genotype-phenotype correlations, most patients carrying the p.D378G mutation had a late-onset, atypical form of PKAN. CONCLUSIONS: We found considerable phenotypic heterogeneity in Korean adults with atypical PKAN. The age of onset may influence the presentation of extrapyramidal symptoms. PMID- 26828214 TI - N30 Somatosensory Evoked Potential Is Negatively Correlated with Motor Function in Parkinson's Disease. AB - OBJECTIVE: The aim of this study was to investigate frontal N30 status in Parkinson's disease (PD) and to examine the correlation between the amplitude of frontal N30 and the severity of motor deficits. METHODS: The frontal N30 was compared between 17 PD patients and 18 healthy volunteers. Correlations between the amplitude of frontal N30 and the Unified Parkinson's Disease Rating Scale (UPDRS) motor score of the more severely affected side was examined. RESULTS: The mean latency of the N30 was not significantly different between patients and healthy volunteers (p = 0.981), but the mean amplitude was lower in PD patients (p < 0.025). There was a significant negative correlation between the amplitude of N30 and the UPDRS motor score (r = -0.715, p = 0.013). CONCLUSIONS: The frontal N30 status indicates the motor severity of PD. It can be a useful biomarker reflecting dopaminergic deficits and an objective measurement for monitoring the clinical severity of PD. PMID- 26828215 TI - Reduced Neck Muscle Strength and Altered Muscle Mechanical Properties in Cervical Dystonia Following Botulinum Neurotoxin Injections: A Prospective Study. AB - OBJECTIVE: To evaluate changes in the strength and mechanical properties of neck muscles and disability in patients with cervical dystonia (CD) during a 12-week period following botulinum neurotoxin (BoNT) injections. METHODS: Eight patients with CD volunteered for this prospective clinical cohort study. Patients had received BoNT injections regularly in neck muscles at three-month intervals for several years. Maximal isometric neck strength was measured by a dynamometer, and the mechanical properties of the splenius capitis were evaluated using two myotonometers. Clinical assessment was performed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) before and at 2, 4, 8, and 12 weeks after the BoNT injections. RESULTS: Mean maximal isometric neck strength at two weeks after the BoNT injections decreased by 28% in extension, 25% in rotation of the affected side and 17% in flexion. At four weeks, muscle stiffness of the affected side decreased by 17% and tension decreased by 6%. At eight weeks, the muscle elasticity on the affected side increased by 12%. At two weeks after the BoNT injections, the TWSTRS-severity and TWSTRS-total scores decreased by 4.3 and 6.4, respectively. The strength, muscle mechanical properties and TWSTRS scores returned to baseline values at 12 weeks. CONCLUSIONS: Although maximal neck strength and muscle tone decreased after BoNT injections, the disability improved. The changes observed after BoNT injections were temporary and returned to pre-injection levels within twelve weeks. Despite having a possible negative effect on function and decreasing neck strength, the BoNT injections improved the patients reported disability. PMID- 26828216 TI - Acute Chorea Onset after Hot Food Consumption in a Patient with Moyamoya Disease. PMID- 26828217 TI - 1987 EUROPEAN MEETINGS OF THE PSYCHOMETRIC SOCIETY: Call For Papers. PMID- 26828218 TI - A Cross-Cultural Replication on Elizur's Facets of Work Values. AB - A slightly refined version of Elizur's (1984) 2-facetted theory on the structure of work values is investigated in this study. Two representative samples of West German adults were asked in 1980 and 1982 to rate the importance of various work outcomes. The intercorrelations of the items of each study can be represented with little error in 2-dimensional SSA spaces. Each configuration shows a perfect correspondence to the unordered work-value facet 'modality' and the ordered facet 'performance-system contingency'. Work values that were defined as either affective, cognitive, or instrumental lead to wedge-like regions emanating from an origin, while those that were classified into one of four categories from 'directly contingent on individual performance' to 'almost independent of individual performance, system-contingent' formed concentric bands around this origin. This confirms Elizur's finding of a radex structure. In spite of this structural invariance, Elizur's Israeli samples differ from ours in the distributions of the importance scores attributed to the various work outcomes. PMID- 26828219 TI - Parameter Sensitivity for Discriminant Analysis. AB - The shape of the response surface associated with a discriminant analysis provides useful insight into the value of the derived optimal discriminant variates. If, for a given set of data, the surface is very peaked at the solution point for a specific variate, the variate is relatively unique in fitting the data. If, conversely, the surface is very flat, the associated optimal variate is not unique for practical purposes, with many other linear combinations providing a fit which is nearly as good as the optimal. A procedure for the determination of "indifference regions", presented and illustrated in this article, allows the assessment of the degree of flatness of the response surface for any analysis. Moreover, when the surface is found to be relatively flat, the results from this procedure can be used to identify alternate variates which are preferable to the optimal because of theoretical consistency while still providing an acceptable empirical fit. PMID- 26828220 TI - Disturbance Term Regression Test Procedures for Recursive and Nonrecursive Models: Solution From Intercorrelation Matrices. AB - The logic and procedures underlying a disturbance term regression test of logical consistency for structural models are reviewed for recursive and nonrecursive designs. It is shown that in a simple three-variable, complete mediational case the test procedure is mathematically equivalent to a part correlation. Procedures are outlined that allow researchers to conduct disturbance term regression tests using only the matrix of intercorrelations among structural variables. General procedures are outlined (a) to test mediational hypotheses in recursive designs and (b) to test for omitted cross effects in nonrecursive designs. The relative virtues of the disturbance term regression test and other fit indices are discussed. PMID- 26828221 TI - A Study of the Comparability of External Criteria for Hierarchical Cluster Analysis. AB - Five external criteria were used to evaluate the extent of recovery of the true structure in a hierarchical clustering solution. This was accomplished by comparing the partitions produced by the clustering algorithm with the partition that indicates the true cluster structure known to exist in the data. The five criteria examined were the Rand, the Morey and Agresti adjusted Rand, the Hubert and Arabie adjusted Rand, the Jaccard, and the Fowlkes and Mallows measures. The results of the study indicated that the Hubert and Arabie adjusted Rank index was best suited to the task of comparison across hierarchy levels. Deficiencies with the other measures are noted. PMID- 26828222 TI - A Confirmatory Factoring of the Self-Consciousness Scale. AB - Fenigstein, Scheier, and Buss (1975) developed a three subscale inventory designed to measure self-consciousness. Burnkrant and Page (1984) used confirmatory factor analysis to evaluate the scale and concluded that five items did not belong to their assigned scales and that one of the original subscales really measured two separable traits. Burnkrant and Page's conclusions may simply reflect incidental properties of the item statistics and could weaken the scale if adopted. Fenigstein et al.'s representation fits the data quite well in its original form. However, items on their social anxiety scale also tend to evoke relatively large variability over subjects and items on their public self consciousness scale tend to evoke relatively little variability. In other words, items on their subscales differ nearly as much statistically as they do substantively. PMID- 26828223 TI - Using Categorical Variables in Discriminant Analysis. AB - Three methods of transforming unordered categorical response variables are described. One is a method using dummy variables. The second method, in which all categorical variables are analyzed simultaneously, is based on an eigenanalysis of frequency patterns scaled relative to within-groups variance, jointly developed by J. E. Overall and J. A. Woodward. With the third method, independently developed by R. A. Fisher and H. O. Lancaster, each categorical variable is analyzed separately with scale values generated so that the grouping variable and the categorical variable are maximally correlated. Results from analyzing two real data sets are used to illustrate the application of the three methods. PMID- 26828224 TI - Analysis of how people with intellectual disabilities organize information using computerized guidance. AB - Access to residential settings for people with intellectual disabilities (ID) contributes to their social participation, but presents particular challenges. Assistive technologies can help people perform activities of daily living. However, the majority of the computerized solutions offered use guidance modes with a fixed, unchanging sequencing that leaves little room for self determination to emerge. The objective of the project was to develop a flexible guidance mode and to test it with participants, to describe their information organization methods. This research used a descriptive exploratory design and conducted a comparison between five participants with ID and five participants with no ID. The results showed a difference in the information organization methods for both categories of participants. The people with ID used more diversified organization methods (categorical, schematic, action-directed) than the neurotypical participants (visual, action-directed). These organization methods varied depending on the people, but also on the characteristics of the requested task. Furthermore, several people with ID presented difficulties when switching from virtual to real mode. These results demonstrate the importance of developing flexible guidance modes adapted to the users' cognitive strategies, to maximize their benefits. Studies using experimental designs will have to be conducted to determine the impacts of more-flexible guidance modes Implications for rehabilitation Intervention approaches favouring, self-determination, decision making, action analysis and results anticipation must be promoted with people with intellectual disabilities. Fixed and rigid technological guidance mode, like those currently favoured in interventions, is appropriate for only some people's profiles or may depend on the nature of the task. It seems that people with ID use a wide spectrum of organization strategies and that adapting guidance modes to all these strategies is relevant. PMID- 26828226 TI - Isolation of 1E4 IgM Anti-Fasciola hepatica Rediae Monoclonal Antibody from Ascites: Comparison of Two Purification Protocols. AB - Purification of immunoglobulin M (IgM) antibodies could be challenging, and is often characterized by the optimization of the purification protocol to best suit the particular features of the molecule. Here, two different schemes were compared to purify, from ascites, the 1E4 IgM monoclonal antibody (mAb) previously raised against the stage of redia of the trematode Fasciola hepatica. This immunoglobulin is used as capture antibody in an immunoenzymatic assay to detect parasite ongoing infection in its intermediate hosts. The first purification protocol of the 1E4 mAb involved two chromatographic steps: an affinity chromatography on a Concanavalin A matrix followed by size exclusion chromatography. An immunoaffinity chromatography was selected as the second protocol for one-step purification of the antibody using the crude extract of adult parasites coupled to a commercial matrix. Immunoreactivity of the fractions during purification schemes was assessed by indirect immunoenzymatic assays against the crude extract of F. hepatica rediae, while purity was estimated by protein electrophoresis. Losses on the recovery of the antibody isolated by the first purification protocol occurred due to protein precipitation during the concentration of the sample and to low resolution of the size exclusion molecular chromatography step regarding this particular immunoglobulin. The immunoaffinity chromatography using F. hepatica antigens as ligands proved to be the most suitable protocol yielding a pure and immunoreactive antibody. The purification protocols used are discussed regarding efficiency and difficulties. PMID- 26828227 TI - A facile three-step total synthesis of tanshinone I. AB - A facile synthetic approach for total synthesis of tanshinone I has been accomplished. The key precursor is a novel compound, epoxy phenanthraquinone. And this synthesis of tanshinone I is achieved in only three simple stages, which include Diels-Alder reaction, Delta(2)-Weitz-Scheffer-type epoxidation, and Feist Benary reaction from commercially available styrene. PMID- 26828225 TI - Cellular mRNA recruits the ribosome via eIF3-PABP bridge to initiate internal translation. AB - IRES-mediated translation of key cell fate regulating genes has been implicated in tumorigenesis. Concerted action of canonical eukaryotic initiation factors and IRES transacting factors (ITAFs) was shown to regulate cellular IRES mediated translation; however, the precise molecular mechanism of ribosome recruitment to cellular IRESes remains unclear. Here we show that the X-linked inhibitor of apoptosis (XIAP) IRES operates in an evolutionary conserved viral like mode and the structural integrity, particularly in the vicinity of AUG, is critical for ribosome recruitment. The binding of eIF3 together with PABP potentiates ribosome recruitment to the IRES. Our data support the model in which eIF3 binds directly to the XIAP IRES RNA in a structure-dependent manner and acts as a scaffold for IRES RNA, PABP and the 40S ribosome. PMID- 26828228 TI - Metabolomics of Delta9-tetrahydrocannabinol: implications in toxicity. AB - Cannabis sativa is the most commonly used recreational drug, Delta(9) tetrahydrocannabinol (Delta(9)-THC) being the main addictive compound. Biotransformation of cannabinoids is an important field of xenobiochemistry and toxicology and the study of the metabolism can lead to the discovery of new compounds, unknown metabolites with unique structures and new therapeutic effects. The pharmacokinetics of Delta(9)-THC is dependent on multiple factors such as physical/chemical form, route of administration, genetics, and concurrent consumption of alcohol. This review aims to discuss metabolomics of Delta(9)-THC, namely by presenting all known metabolites of Delta(9)-THC described both in vitro and in vivo, and their roles in the Delta(9)-THC-mediated toxic effects. Since medicinal use is increasing, metabolomics of Delta(9)-THC will also be discussed in order to uncover potential active metabolites that can be made available for this purpose. PMID- 26828229 TI - Development of Polymorphic Microsatellite Loci for Potato Wart from Next Generation Sequence Data. AB - Synchytrium endobioticum is the fungal agent causing potato wart disease. Because of its severity and persistence, quarantine measures are enforced worldwide to avoid the spread of this disease. Molecular markers exist for species-specific detection of this pathogen, yet markers to study the intraspecific genetic diversity of S. endobioticum were not available. Whole-genome sequence data from Dutch pathotype 1 isolate MB42 of S. endobioticum were mined for perfect microsatellite motifs. Of the 62 selected microsatellites, 21 could be amplified successfully and displayed moderate levels of polymorphism in 22 S. endobioticum isolates from different countries. Nineteen multilocus genotypes were observed, with only three isolates from Canada displaying identical profiles. The majority of isolates from Canada clustered genetically. In contrast, most isolates collected in Europe show no genetic clustering associated with their geographic origin. S. endobioticum isolates with the same pathotype displayed highly variable genotypes and none of the microsatellite markers correlated with a specific pathotype. The markers developed in this study can be used to assess intraspecific genetic diversity of S. endobioticum and allow track and trace of genotypes that will generate a better understanding of the migration and spread of this important fungal pathogen and support management of this disease. PMID- 26828230 TI - Shade Effects on the Dispersal of Airborne Hemileia vastatrix Uredospores. AB - Hemileia vastatrix caused a severe epidemic in Central America in 2012-13. The gradual development of that epidemic on nearly a continental scale suggests that dispersal at different scales played a significant role. Shade has been proposed as a way of reducing uredospore dispersal. The effect of shade (two strata: Erythrina poeppigiana below and Chloroleucon eurycyclum above) and full sun on H. vastatrix dispersal was studied with Burkard traps in relation to meteorological records. Annual and daily patterns of dispersal were observed, with peaks of uredospore capture obtained during wet seasons and in the early afternoon. A maximum of 464 uredospores in 1 day (in 14.4 m(3) of air) was recorded in October 2014. Interactions between shade/full sun and meteorological conditions were found. Rainfall, possibly intercepted by tree cover and redistributed by raindrops of higher kinetic energy, was the main driver of uredospore dispersal under shade. Wind gusts reversed this effect, probably by inhibiting water accumulation on leaves. Wind gusts also promoted dispersal under dry conditions in full sun, whereas they had no effect under shaded conditions, probably because the canopy blocked the wind. Our results indicate the importance of managing shade cover differentially in rainy versus dry periods to control the dispersal of airborne H. vastatrix uredospores. PMID- 26828231 TI - Verticillium dahliae Infects, Alters Plant Biomass, and Produces Inoculum on Rotation Crops. AB - Verticillium wilt, caused by Verticillium dahliae, reduces yields of potato and mint. Crop rotation is a potential management tactic for Verticillium wilt; however, the wide host range of V. dahliae may limit the effectiveness of this tactic. The hypothesis that rotation crops are infected by V. dahliae inoculum originating from potato and mint was tested by inoculation of mustards, grasses, and Austrian winter pea with eight isolates of V. dahliae. Inoculum density was estimated from plants and soil. Typical wilt symptoms were not observed in any rotation crop but plant biomass of some crops was reduced, not affected, or increased by infection of specific isolates. Each isolate was host-specific and infected a subset of the rotation crops tested but microsclerotia from at least one isolate were observed on each rotation crop. Some isolates were host-adapted and differentially altered plant biomass or produced differential amounts of inoculum on rotation crops like arugula and Austrian winter pea, which supported more inoculum of specific isolates than potato. Evidence of asymptomatic and symptomatic infection and differential inoculum formation of V. dahliae on rotation crops presented here will be useful in designing rotations for management of Verticillium wilt. PMID- 26828232 TI - Lettuce chlorosis virus P23 Suppresses RNA Silencing and Induces Local Necrosis with Increased Severity at Raised Temperatures. AB - RNA silencing functions as an antivirus defense strategy in plants, one that plant viruses counter by producing viral suppressors of RNA silencing (VSRs). VSRs have been identified in three members of the genus Crinivirus but they do not all share identical suppression mechanisms. Here, we used Agrobacterium co infiltration assays to investigate the suppressor activity of proteins encoded by Lettuce chlorosis virus (LCV). Of 7 LCV proteins (1b, P23, HSP70 homolog, P60, CP, CPm, and P27) tested for the suppression of silencing of green fluorescent protein (GFP) expression in wild-type Nicotiana benthamiana plants, only P23 suppressed the onset of local silencing. Small-interfering (si)RNA accumulation was reduced in leaves co-infiltrated with P23, suggesting that P23 inhibited the accumulation or enhanced the degradation of siRNA. P23 also inhibited the cell-to cell and systemic movement of RNA silencing in GFP-expressing transgenic N. benthamiana plants. Expression of P23 via agroinfiltration of N. benthamiana leaves induced local necrosis that increased in severity at elevated temperatures, a novelty given that a direct temperature effect on necrosis severity has not been reported for the other crinivirus VSRs. These results further affirm the sophistication of crinivirus VSRs in mediating the evasion of host's antiviral defenses and in symptom modulation. PMID- 26828233 TI - Evaluation of Intraocular Inflammation with Laser Flare Photometry in Behcet Uveitis. AB - PURPOSE: To evaluate the association between intraocular inflammation and laser flare photometry measurements in Behcet disease. METHODS: In total, 45 patients were included in the study. The retrospective chart reviews of patients were performed. The flare levels were compared with the grade of anterior chamber cells, the presence of vitreous cells, the complications of uveitis, and fluorescein angiography scores. RESULTS: The attack group had higher flare intensity; the flare levels were higher in both groups compared with the values of healthy controls. The flare levels were related to the grade of the anterior chamber cells, the presence of vitreous cells and the fluorescein angiography scores. Patients with optic atrophy and/or maculopathy also had higher values. Higher flare values were correlated with poor vision. CONCLUSIONS: Laser flare photometry may reduce the necessity of fluorescein angiography in monitoring subclinical inflammation and may be an indicator of posterior segment activity when fluorescein angiography is not applicable. PMID- 26828236 TI - Fear-Avoidance Beliefs and Chronic Pain. AB - Fear-avoidance (FA) beliefs are significantly associated with the experience of pain, especially when the pain becomes chronic in nature. The anticipated threat of intense pain will often result in the constant vigilance and monitoring of pain sensations, which, in turn, can cause even low-intensity sensations of pain to become unbearable for the person. Just the anticipation of increased pain or reinjury can further stimulate avoidance behaviors. A vicious cycle may develop, in which fears of increased pain or reinjury contribute to the avoidance of many activities, leading to inactivity and, ultimately, to greater disability. Anyone who assesses and treats pain-related disability should also be prepared to assess and treat pain-related FA. PMID- 26828234 TI - Evaluation of intra-articular injection of autologous platelet lysate (PL) in horses with osteoarthritis of the distal interphalangeal joint. AB - BACKGROUND: Regenerative medicine has become one of the most promising therapies of equine osteoarthritis. Platelet lysate (PL) is rich in bioactive proteins and growth factors that play a crucial role in tissue healing. OBJECTIVE: To evaluate the efficacy of intra-articularly injected autologous PL in equine athletes with naturally occurring osteoarthritis. ANIMALS AND METHODS: Fifteen warmblood geldings aged 8-19 years with osteoarthritis of the distal interphalangeal joint were included in this study. They were randomly divided into two groups; 10 horses received intra-articular injections of PL and 5 of normal saline (controls). Before treatment, platelet-derived growth factor (PDGF) levels in basal plasma and prepared PL were estimated. Each joint was injected twice within a three-week period. Lameness was evaluated using the American Association of Equine Practitioners grading system, before treatment and 10 days after each intra-articular injection. Horses were examined fortnightly for one year. Radiographic examination was performed six months post-treatment. The generalized estimating equation test was used for statistical analysis. RESULTS: Acceptable levels of PDGF were detected in PLs (mean +/- SD: 258.0 +/- 52.3 pg/ml). The majority of horses (9/10) responded positively to PL treatment presenting lower lameness grades (p < 0.0005) compared to controls 10 days after the second injection, and returned to normal athletic activity. Radiographs revealed no changes in osteoarthritis lesions six months after treatment. One year post injections, however, all horses relapsed to their initial degree of lameness. CONCLUSION: Intra-articularly injected autologous PL is an efficient method for temporarily managing osteoarthritis of the distal interphalangeal joint in athletic horses. PMID- 26828237 TI - Identification of Metastatic Lesions in a Patient With Low Back Pain Following a Motor Vehicle Collision. AB - A 58-year-old man was referred to physical therapy with a primary complaint of intermittent low back pain (LBP) 2 weeks after being in a motor vehicle collision. The absence of red flags justified the initiation of treatment, but when symptoms of unrelenting LBP emerged, he was referred to his primary care physician with a request for further medical workup. Before further imaging work up was performed, the patient presented to the emergency room with a urinary complaint; this, in combination with unrelenting LBP, prompted further imaging follow-up. Lumbar/thoracic spine magnetic resonance imaging revealed multiple compression fractures and diffuse bone marrow heterogeneity consistent with a malignant infiltrative marrow process. The patient underwent additional laboratory testing and a bone marrow aspirate and biopsy that confirmed the diagnosis of multiple myeloma. PMID- 26828238 TI - Analysis of Organic Anionic Surfactants in Fine and Coarse Fractions of Freshly Emitted Sea Spray Aerosol. AB - The inclusion of organic compounds in freshly emitted sea spray aerosol (SSA) has been shown to be size-dependent, with an increasing organic fraction in smaller particles. Here we have used electrospray ionization-high resolution mass spectrometry in negative ion mode to identify organic compounds in nascent sea spray collected throughout a 25 day mesocosm experiment. Over 280 organic compounds from ten major homologous series were tentatively identified, including saturated (C8-C24) and unsaturated (C12-C22) fatty acids, fatty acid derivatives (including saturated oxo-fatty acids (C5-C18) and saturated hydroxy-fatty acids (C5-C18), organosulfates (C2-C7, C12-C17) and sulfonates (C16-C22). During the mesocosm, the distributions of molecules within some homologous series responded to variations among the levels of phytoplankton and bacteria in the seawater. The average molecular weight and carbon preference index of saturated fatty acids significantly decreased within fine SSA during the progression of the mesocosm, which was not observed in coarse SSA, sea-surface microlayer or in fresh seawater. This study helps to define the molecular composition of nascent SSA and biological processes in the ocean relate to SSA composition. PMID- 26828239 TI - Mallotojaponins B and C: Total Synthesis, Antiparasitic Evaluation, and Preliminary SAR Studies. AB - The first total syntheses of mallotojaponin B and C as well as several analogues have been achieved. Biological evaluation of the synthesized compounds against Plasmodium falciparum and Trypanosoma brucei have also been carried out. PMID- 26828240 TI - Increased volume of conducting airways in idiopathic pulmonary fibrosis is independent of disease severity: a volumetric capnography study. AB - Bronchiectasis, bronchiolectasis, and bronchiolisation of alveolar regions are salient features of idiopathic pulmonary fibrosis (IPF). We asked whether IPF was associated with physiological changes consistent with increases in the volume of conducting airways, and whether airway volume was related to the severity of lung fibrosis. Patients with IPF (N = 57, vital capacity-VC: 73 +/- 20%), patients with non-IPF interstitial lung disease (non-IPF ILD, N = 24, VC = 78 +/- 18%) and controls without lung disease (N = 51, VC = 112 +/- 21%) underwent volumetric capnography for the determination of conducting airway volume using Fletcher's equal area method, reported to predicted total lung capacity to control for the effect of lung size (VDaw/TLCp, mL/L). VDaw/TLCp was higher in patients with IPF (45.3 +/- 12.8 ml L(-1)) in comparison with controls (34.2 +/- 11.0 ml L(-1), p < 0.0001) and patients with non-IPF ILD (39.5 +/- 9.2 ml L(-1), p = 0.0496). The same differences were observed when analysis was restricted to subjects with moderate IPF (VC ? 80% predicted). Among IPF patients, VDaw/TLCp was correlated with neither the mMRC dyspnea scale, nor VC, nor carbon monoxide transfer factor, nor computed tomography fibrosis scores. Volumetric capnography showed higher conducting airway volume in IPF patients in comparison with controls and non-IPF ILDs, independent of disease severity. This result is consistent with either anatomical predisposition or dilation/longitudinal growth of conducting airways in IPF. PMID- 26828241 TI - Assessing risk factors of sporadic Campylobacter infection: a case-control study in Arizona. AB - Case-control studies of sporadic Campylobacter infections have predominately been conducted in non-Hispanic populations. In Arizona, rates of campylobacteriosis have been historically higher than the national average, with particularly high rates in Hispanics. In 2010, health departments and a state university collaborated to conduct a statewide case-control study to determine whether risk factors differ in an ethnically diverse region of the United States. Statistically significant risk factors in the final multivariate model were: eating cantaloupe [odds ratio (OR) 7.64], handling raw poultry (OR 4.88) and eating queso fresco (OR 7.11). In addition, compared to non-Hispanic/non travellers, the highest risk group were Hispanic/non-travellers (OR 7.27), and Hispanic/travellers (OR 5.87, not significant). Results of this study suggest Hispanics have higher odds of disease, probably due to differential exposures. In addition to common risk factors, consumption of cantaloupe was identified as a significant risk factor. These results will inform public health officials of the varying risk factors for Campylobacter in this region. PMID- 26828243 TI - The Ineffectiveness of Tacrolimus in an Infant With a Mutation in the IL-10 Receptor. PMID- 26828245 TI - How should occupational anaphylaxis be investigated and managed? AB - PURPOSE OF REVIEW: Anaphylaxis is a systemic allergic reaction that can be life threatening or fatal and can result from work-related exposures. This review study focuses on the assessment, main triggers, and management of occupational anaphylaxis. RECENT FINDINGS: Exposed workers can be sensitized through inhalation and skin contact, and the risks increase with penetration of the allergen through the skin. The main eliciting agents of occupational anaphylaxis include stinging insects and animal bites, natural rubber latex and other vegetable allergens, food products, and drugs. Workers sensitized to occupational allergens may also develop anaphylaxis outside the work environment from exposure to the same or to cross-reacting allergens. Cofactors at work such as exercise may increase the risk. The relevant medical records and laboratory tests (e.g. tryptase) performed during the episode should be reviewed. SUMMARY: It is very important to confirm the diagnosis and to identify the specific trigger of anaphylaxis. Component-resolved diagnosis may help in the identification of primary sensitizers or cross-reactive allergens. Adrenaline must be administered to all patients experiencing anaphylaxis. Removal from exposure is mandatory to prevent further episodes. A written emergency management plan, health and safety education, and training and surveillance should be enforced in occupations at greater risk. PMID- 26828244 TI - Isolated Peripancreatic Necrosis in Acute Pancreatitis Is Infrequent and Leads to Severe Clinical Course Only When Extensive: A Prospective Study From a US Tertiary Center. AB - GOALS: To explore the diagnostic challenges, management, and clinical outcomes of patients with isolated peripancreatic necrosis (PPN), with emphasis on the extent of involvement, and compare them to pancreatic necrosis (PN). BACKGROUND: PPN, a relatively new term, has been included as a separate entity in the Revised Atlanta Classification. STUDY: Clinical data of recruited acute pancreatitis patients were recorded prospectively. Contrast-enhanced computed tomographic scans were reviewed by expert radiologists blinded to clinical outcomes. RESULTS: In total, 271 of the 400 acute pancreatitis patients underwent contrast-enhanced computed tomography, of which 29 (11%) had PPN (14: limited; 15: extensive) and 124 (46%) PN (40: <30%, 16: 30% to 50%, 68: >50% of parenchyma). Patients with PPN were similar to PN in age (56 y), gender (55% male), and body mass index (29 kg/m(2)). Nutritional support was provided in 18 (62%) patients with PPN and 97 (78%) with PN (P=0.12). Drainage/debridement was required in 2 patients (7%) with PPN and 64 (53%) with parenchymal necrosis (P<0.001). Persistent organ failure rates did not differ significantly (34% vs. 51%, P=0.17), but hospital stay was shorter in patients with PPN (15 vs. 20 d, P=0.05). Limited PPN required no intervention and had similar persistent organ failure rates and hospitalization length with interstitial pancreatitis (both P>=0.12). Extensive PPN mainly developed in patients with persistent organ failure (60%) and rarely required drainage (2/15). CONCLUSIONS: PPN prevalence was lower than PN with a ratio of 1:4. PPN rarely required intervention. Utilizing the extent of involvement has the potential to classify PPN and PN with escalating clinical significance and guide management. PMID- 26828246 TI - Predicting outcomes of decompressive craniectomy: use of Rotterdam Computed Tomography Classification and Marshall Classification. AB - BACKGROUND: Data on the evaluation of the Rotterdam Computed Tomography Classification (RCTS) as a predictor of outcomes in patients undergoing decompressive craniectomy (DC) for trauma is limited and lacks clarity. OBJECTIVE: To explore the role of RCTS in predicting unfavourable outcomes, including mortality in patients undergoing DC for head trauma. METHODS: This was an observational cohort study conducted from 1 January 2009 to 31 March 2013. CT scans of adults with head trauma prior to emergency DC were scored according to RCTS. A receiver operating characteristic curve analysis was performed to identify the optimal cut-off RCTS for predicting unfavourable outcomes [Glasgow outcome scale (GOS) = 1-3]. Binary logistic regression analysis was performed to evaluate the relationship between RCTS and unfavourable outcomes including mortality. RESULTS: One hundred ninety-seven patients (mean age: 31.4 +/- 18.7 years) were included in the study. Mean Glasgow coma score at presentation was 8.1 +/- 3.6. RCTS was negatively correlated with GOS (r = -0.370; p < 0.001). The area under the curve was 0.687 (95% CI: 0.595-0.779; p < 0.001) and 0.666 (95% CI: 0.589-0.742; p < 0.001) for mortality and unfavourable outcomes, respectively. RCTS independently predicted both mortality (adjusted odds ratio for RCTS >3 compared with RCTS <=3: 2.792, 95% CI: 1.235-6.311) and other unfavourable outcomes (adjusted odds ratio for RCTS >3 compared with RCTS <=3: 2.063, 95% CI: 1.056-4.031). CONCLUSION: RCTS is an independent predictor of unfavourable outcomes and mortality among patients undergoing emergency DC. PMID- 26828247 TI - Analysis of risk factor and clinical characteristics of angiodysplasia presenting as upper gastrointestinal bleeding. AB - BACKGROUND/AIMS: Angiodysplasia is important in the differential diagnosis of upper gastrointestinal bleeding (UGIB), but the clinical features and outcomes associated with UGIB from angiodysplasia have not been characterized. We aimed to analyze the clinical characteristics and outcomes of angiodysplasia presented as UGIB. METHODS: Between January 2004 and December 2013, a consecutive series of patients admitted with UGIB were retrospectively analyzed. Thirty-five patients with bleeding from angiodysplasia were enrolled. We compared them with an asymptomatic control group (incidental finding of angiodysplasia in health screening, n = 58) and bleeding control group (simultaneous finding of angiodysplasia and peptic ulcer bleeding, n = 28). RESULTS: When patients with UGIB from angiodysplasia were compared with the asymptomatic control group, more frequent rates of nonantral location and large sized lesion (>= 1 cm) were evident in multivariate analysis. When these patients were compared with the bleeding control group, they were older (mean age: 67.94 +/- 9.16 years vs.55.07 +/- 13.29 years, p = 0.03) and received less transfusions (p = 0.03). They also had more frequent rate of recurrence (40.0% vs. 20.7%, p = 0.02). CONCLUSIONS: Non-antral location and large lesions (>= 1 cm) could be risk factors of UGIB of angiodysplasia. UGIB due to angiodysplasia was more common in older patients. Transfusion requirement would be less and a tendency of clinical recurrence might be apparent. PMID- 26828248 TI - Paraneoplastic dermatomyositis presenting myopathy combined with synchronous cervical and sigmoid colon cancer. PMID- 26828249 TI - Ectopic ACTH syndrome caused by pulmonary carcinoid tumor mimicking long-standing sclerosing hemangioma. PMID- 26828250 TI - Widespread intracranial calcifications in a patient with hypoparathyroidism. PMID- 26828251 TI - Rival Hypotheses in Linear Structure Modeling: Factor Rotation in Confirmatory Factor Analysis and Latent Path Analysis. AB - After summarizing Algina's (1980) criteria for factor identification in confirmatory factor analysis (CFA) a procedure is given how to determine rotationally underidentified factors by adding further restrictions and how to carry out the rotation to meet the old restrictions together with the additional ones. As CFA may also be part of a more complex structure, for example, in latent path analysis, where CFA usually is employed as measurement model for the latent variables, the next section considers the effects of rotation in the measurement model on the latent path coefficients in the inner part of a latent path model. A last section presents two illustrative examples. The procedure presented may be used in theory based model building to develop an identified model. If there is not enough prior knowledge to make the whole structure identifiable, the procedure may be used in an exploratory way, adding various sets of identifying restrictions in turn to produce alternative models, which may be subject to further investigation. PMID- 26828252 TI - Computational Formulas for Multivariate Strength of Association from Approximate F and chi(2) Tests. AB - There are numerous occasions, in conducting a priori, prospective power analyses for example, in which a measure of multivariate strength of association is desired but cannot be recovered from published research reports. Measures of multivariate strength of association, defined as a function of the eigenvalues of Q(-1) EQH or (QE + QH)(-1)QH, may be computed in conjunction with any of four multivariate test statistics. A large majority of research publications that perform multivariate analyses do not report a measure of strength of association, nor do they report sufficient information to compute multivariate measures of strength of association. Most manuscripts, however, do typically report F-test or chi(2) approximations with associated degrees of freedom. In this article we develop computational formulas for recovering measures of strength of association from approximate F and chi(2) tests associated with four multivariate test statistics. PMID- 26828253 TI - Cross-Sectional Time Series Designs: A General Transformation Approach. AB - Cross-sectional time series designs assess the generalizability of intervention effects across different units. The general transformation approach to time series analysis was proposed by Velicer and McDonald (1984) to avoid the model identification step. A general transformation matrix is employed for all analyses rather than the specific matrix associated with a particular model. This article extends the general transformation matrix approach to the analysis of multiple unit data by the development of a patterned transformation matrix. A sequence of tests of the parameters permits the assessment of between unit differences. The resulting procedure includes several alternative approaches as special cases and is easily implemented with only minor revisions in existing computer software. PMID- 26828254 TI - A Bootstrap Confidence Interval Based on a Correlation Corrected for Range Restriction. AB - The sample correlation coefficient corrected for range restriction was bootstrapped to obtain a confidence interval on the unrestricted population correlation, rho. The technique was evaluated using a computer simulation under different values of rho and four distributions (normal, mixed, positively skewed and negatively skewed). The corrected correlation coefficient yielded accurate bootstrap intervals over the four distributions. On the average, the size of rho did not affect the accuracy of the confidence interval. However, it did affect stability. The interval behaved rather erratically when rho was small (.1) and sample size was small. Sample size was found to be the most important factor in determining accuracy and stability. Overall, the results suggest that bootstrapping the corrected correlation coefficient is a reliable method for obtaining a confidence interval on rho especially when the sample size is moderate to large (n > 50). PMID- 26828255 TI - The 16PF Related to the Five-Factor Model of Personality: Multiple-Indicator Measurement versus the A Priori Scales. AB - This article examines the Sixteen Personality Factor Inventory (16PF; Cattell, Eber, & Tatsuoka, 1970) in terms of recent methodological and substantive developments: restricted (confirmatory) factor analysis and the five-factor model of personality as operationalized by the NEO-PI (NEO Personality Inventory). A multiple-indicator measurement model of the 16PF was constructed and analyzed with a restricted factor analysis and then cross-validated with a confirmatory analysis on a new sample. The relations of the a priori 16PF scales and the derived scales with the NEO-PI were investigated with comparative canonical correlation analyses. Both the a priori and derived 16PF scales demonstrated strong relationships to the NEO-PI scales, with the canonical correlations for the a priori scales slightly larger. These findings lead to the conclusion that the original 16PF remains robust in the context of these more recent developments. PMID- 26828256 TI - Empirical Bayes Approaches to Multivariate Fuzzy Partitions. AB - In describing high dimensional discrete response data, mathematical and statistical issues arise that require multivariate procedures that are not based on normal distributions, that is, the mathematical representation of high dimensional discrete response data (Event Spaces) requires a representation in lower dimensional parameter spaces consistent with the discrete properties of the Event Space. Mapping discrete responses to latent discrete classes has the limitation of not representing real individual variation within the categories. The use of a fuzzy partition model is proposed which describes individuals in terms of partial membership in multiple latent categories which represents bounded discrete event spaces with significant third and higher order moments. We discuss statistical issues arising in identifying both the deterministic and the stochastic variation of data when applications involve systematic variation due to observed and unobserved variables. We present an empirical Bayes-maximum likelihood estimation scheme for the application of the fuzzy partition models. PMID- 26828257 TI - A Comparison of Pattern Matching Indices. AB - A common problem in multivariate applications is the comparison of pattern matrices obtained from two independent studies. We compared the performance of four pattern matching indices (the coefficient of congruence [c], the s-statistic [s], Pearson's r [r], and kappa [k]) under a variety of experimental conditions. We constructed population pattern matrices by varying (a) saturation or the size of the loadings, (b) sample size, (c) the number of observed variables, and (d) the number of derived variables. Sample patterns were computer generated and matched, employing each index, to their population pattern. With the exception of r, little difference in matching performance between indices was observed. In general, an increase in either saturation or sample size resulted in more accurate index values. PMID- 26828258 TI - Using the Analytic Hierarchy Process to Analyze Multiattribute Decisions. AB - Since its introduction a decade ago, the Analytic Hierarchy Process (AHP) has been used by decision makers in many contexts. The vast majority of these applications has involved allocating resources or making choices from among alternatives. This article discusses how AHP may be used in a different manner: to assist researchers in the analysis of decisions. AHP is briefly compared with other decision-analysis techniques, such as multiattribute utility measurement, conjoint measurement, and general linear models (regression and analysis of variance). Some of the possible insights into decision processes that can be obtained using AHP are illustrated with data gathered from practicing auditors of financial statements. PMID- 26828259 TI - Rater Reliability: A Maximum Likelihood Confirmatory Factor-Analytic Approach. AB - A procedure for evaluating a variety of rater reliability models is presented. A multivariate linear model is utilized to describe and assess a set of ratings. The parameters of such a model are reexpressed in terms of a factor-analytic model. Maximum likelihood methods are employed to estimate and test the parameters in this factor-analytic model. The approach is related to the use of the intraclass correlation coefficient to estimate reliability. Two examples are presented, and the results contrasted to those found with an intraclass correlation approach. Extensions of the procedure to multiple sets of judges, multiple measures, and multiple groups is introduced. PMID- 26828260 TI - Electrotransfer of the tilapia piscidin 3 and tilapia piscidin 4 genes into skeletal muscle enhances the antibacterial and immunomodulatory functions of Oreochromis niloticus. AB - Tilapia piscidin 3 (TP3) and tilapia piscidin 4 (TP4) are antimicrobial peptides recently isolated from Oreochromis niloticus. We previously showed that synthetic TP3 and TP4 possessed antimicrobial activities. Here, we analyzed the bactericidal abilities and immunomodulatory properties of these AMPs following the electroporation of pCMV-GFP-TP3 or pCMV-GFP-TP4 plasmid into tilapia (O. niloticus) muscle and subsequent infection with Vibrio vulnificus or Streptococcus agalactiae. Prior overexpression of TP3 or TP4 in tilapia muscle tissues efficiently reduced bacterial numbers at 24 and 48 h after V. vulnificus infection and reduced bacterial numbers at 24 h after S. agalactiae infection compared to numbers in controls expressing pCMV-GFP (EGFP). Electroporation of pCMV-EGFP-TP3 (TP3) or pCMV-EGFP-TP4 (TP4) significantly increased expression of several immune-related genes in muscle (IL-1beta (12 h, TP3), IL-8 (12 h, TP3), TGFbeta (3 h, TP4), and IkappaB (48 h, TP3, TP4)) and decreased the expression of TLR5 (12 h and 24 h, TP3) after V. vulnificus infection. Following S. agalactiae infection, expression of the following genes was significantly decreased in muscle: IL-1beta (12 h, TP3), IL-8 (12 h, TP3, TP4), TLR5 (3 h-24 h, TP3, TP4), TGFbeta (3 h, TP4; 24 h, TP3, TP4), and IkappaB (3 h, TP3). These data suggest that TP3 and TP4 exert antimicrobial effects after overexpression in the O. niloticus muscle, and also play important roles in the regulation of immune related gene expression. PMID- 26828261 TI - Molecular cloning, characterization and mRNA expression of six peroxiredoxins from Black carp Mylopharyngodon piceus in response to lipopolysaccharide challenge or dietary carbohydrate. AB - Peroxiredoxin (Prx) belongs to a cellular antioxidant protein family that plays important roles in innate immune function and anti-oxidative capability. In the present study, six Prxs were cloned from Black carp Mylopharyngodon piceus (MpPrx) by homology cloning and rapid amplification of cDNA ends (RACE) techniques. There were 199, 197, 250, 260, 189 and 222 amino acids in six MpPrxs, respectively. BLAST analysis reveals that MpPrxs shares high identities and similar characteristics with other known Prxs from animals. The phylogenetic analysis evidenced three major subclasses corresponding to one-Cys-Prx (MpPrx6), typical two-Cys-Prx (MpPrx1-4) and atypical 2-Cys-Prx (MpPrx5) that reflected the present hierarchy of vertebrates and invertebrates. Although six MpPrxs are constitutively expressed in all tissues, relatively higher-level mRNA expression levels of six MpPrxs can be detected in liver, eyes, heart and adipose tissues by real-time PCR assays. The transcriptional patterns of six MpPrxs mRNA in liver were detected by real-time PCR in Black carp after lipopolysaccharide (LPS) challenge and treated with graded levels of dietary carbohydrate (CHO) (106.5, 194.3, 288.4 and 379.1 g kg(-1)), respectively. These results showed that stimulation with LPS could induce up-expression of six MpPrxs mRNA, and the variations of MpPrx4 were more sensitive than these of other MpPrxs in the liver of Black carp. Compared with those in group with 106.5 g kg(-1) dietary CHO, the expression levels of MpPrx2, MpPrx3 and MpPrx6 were significantly down-regulated while MpPrx5 were significantly induced in liver of Black carp fed with adequate dietary CHO (194.3 g kg(-1)). In addition, significant up-regulations of MpPrx2, MpPrx3 and MpPrx6 were observed in Black carp fed with excessive dietary CHO (379.1 g kg(-1)). And MpPrx4 could be constantly induced with increasing dietary CHO contents in this study. These results indicated that MpPrxs were constitutive and inducible proteins and might play important roles in innate immune function after LPS challenge and regulating redox homeostasis in the metabolism of dietary CHO. PMID- 26828262 TI - Accumulation of cells expressing macrophage colony-stimulating factor receptor gene in the ovary of a pregnant viviparous fish, Neoditrema ransonnetii (Perciformes, Embiotocidae). AB - Macrophage colony-stimulating factor receptor (M-CSFR), a member of the group of type III protein tyrosine kinase receptors, is expressed primarily by monocyte/macrophage lineage cells. In order to describe the distribution of macrophages at the maternal-fetal interface in Neoditrema ransonnetii, a viviparous fish species, M-CSFR cDNA was sequenced. Two sequences were obtained: NrM-CSFR1 (4381 bp, encoding 980 amino acids), and NrM-CSFR2 (3573 bp, encoding 1016 amino acids). Both the genes were expressed in the ovary of pregnant females. In situ hybridization revealed that a number of cells that were positive for NrM-CSFR1 and/or NrM-CSFR2 populated the ovigerous lamellae of the ovary during pregnancy. Following parturition, M-CSFR-positive cells disappeared from the subepithelial region of ovigerous lamellae, and were localized in perivascular tissues. These results suggest the role of M-CSFR-positive cells, which appear to be macrophages, in N. ransonnetii during pregnancy. PMID- 26828263 TI - A novel C-type lectin, Nattectin-like protein, with a wide range of bacterial agglutination activity in large yellow croaker Larimichthys crocea. AB - C-type lectins (CTLs) are generally recognized as a superfamily of Ca(2+) dependent carbohydrate-binding proteins, which serve as pattern recognition receptors (PRRs) in innate immunity of vertebrates. In this study, the molecular characterization and immune roles of a novel CTL from Larimichthys crocea (designated as LcNTC) were investigated. LcNTC is a novel protein that shared 33% 49% homology with other teleosts CTLs. The full-length cDNA of LcNTC was composed of 859 bp with a 465 bp open reading frame encoding a putative protein of 154 residues. LcNTC contained a single CRD with four conserved disulfide-bonded cysteine residues (Cys(57)-Cys(148), Cys(126)-Cys(140)) and EPN/AND motifs instead of invariant EPN/WND motifs required for carbohydrate-binding specificity and constructing Ca(2+)-binding sites. LcNTC mRNA was detected in all examined tissues with the most abundant in the gill. After challenged with poly I:C and Vibrio parahaemolyticus, the temporal expression of LcNTC was significantly up regulated in the liver, spleen and head-kidney. LcNTC transcripts were also induced in the gill, skin, spleen and head-kidney post-infection with Cryptocaryon irritans. The recombinant LcNTC (rLcNTC) purified from Escherichia coli BL21 (DE3) exhibited strong agglutination activity against erythrocytes from human, rabbit and large yellow croaker in a Ca(2+)-dependent manner, and the agglutination could be inhibited by D-Mannose, D-Glucose, D-Fructose, alpha Lactose, D-Maltose and LPS. Positive microbial agglutination activities of rLcNTC were observed against all tested bacteria in the presence of Ca(2+), including Gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus and Micrococcus lysoleikticus) and Gram-negative bacteria (E. coli, V. parahaemolyticus, Vibrio alginolyticus and Aeromonas hydrophila). These findings collectively indicated that LcNTC might be involved in the innate immunity of L. crocea as a PRR. PMID- 26828264 TI - Intensity of treadmill walking exercise on acute mood symptoms in persons with multiple sclerosis. AB - BACKGROUND/OBJECTIVES: An acute bout of moderate-intensity treadmill walking exercise has previously been associated with improvements in overall mood disturbance and vigor, without worsening fatigue, among persons with multiple sclerosis (MS).This study examined the effects of light-, moderate-, and high intensity bouts of treadmill walking exercise on immediate and delayed mood states in MS. DESIGN: This was a within-subjects, randomized, and counter balanced study. METHODS: 23 women and 1 man with MS undertook 20-minute bouts of light-, moderate-, and high-intensity treadmill walking, and seated quiet rest. Participants completed the profile of mood states (POMS) questionnaire before, immediately after, and 45 minutes after each condition. Total mood disturbance (TMD) and six subscales of the POMS were analyzed using 2-way, repeated-measures analysis of variance (ANOVA). RESULTS: There was a significant condition-by-time interaction on TMD scores ([Formula: see text]) and vigor scores ([Formula: see text]). The moderate-intensity treadmill walking yielded the largest improvements in TMD and vigor immediately post-condition (p < .05). These improvements were no longer significant at 45 minutes post-condition (p > .05). CONCLUSION: TMD and vigor improved immediately after moderate-intensity walking, but the changes dissipated over time. Fatigue did not worsen after any of the walking conditions. These results indicate that an acute bout of moderate-intensity walking may help with mood management in persons with MS, without worsening fatigue. PMID- 26828265 TI - The oncoprotein HBXIP up-regulates FGF4 through activating transcriptional factor Sp1 to promote the migration of breast cancer cells. AB - We have reported that the oncoprotein hepatitis B X-interacting protein (HBXIP) is able to promote migration of breast cancer cells. Fibroblast growth factor 4 (FGF4) is a multipotent growth factor and is highly expressed in various human cancers. However, the regulatory mechanism of FGF4 in breast cancer remains poorly understood. In the present study, we report that HBXIP is able to up regulate FGF4 to enhance the migration of breast cancer cells. Immunohistochemistry staining showed that HBXIP and FGF4 were highly expressed in clinical metastatic lymph nodes of breast tumor. The expression levels of HBXIP were positively related to those of FGF4 in clinical breast cancer tissues. Then, we validated that HBXIP up-regulated the expression of FGF4 at the levels of promoter, mRNA and protein by luciferase reporter gene assays, reverse transcription-polymerase chain reaction and Western blot analysis. Moreover, we found that HBXIP was able to activate FGF4 promoter through transcriptional factor Sp1 by luciferase reporter gene assays. Chromatin immunoprecipitation assays confirmed that HBXIP coactivated Sp1 to stimulate FGF4 promoter. In function, we showed that HBXIP promoted breast cancer cell migration through FGF4 by wound healing and transwell cell migration assays. Thus, we conclude that the oncoprotein HBXIP up-regulates FGF4 through activating transcriptional factor Sp1 to promote the migration of breast cancer cells. Therapeutically, HBXIP may serve as a novel target in breast cancer. PMID- 26828266 TI - Pathophysiological role of osteopontin and angiotensin II in atherosclerosis. PMID- 26828267 TI - AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo. AB - The AGC kinase family is important cell proliferation and survival. Dysregulation of this family contributes to gastric cancer progression. Here, we evaluated the potential activity of AT13148, a first-in-class multi-AGC kinase inhibitor, against gastric cancer cells. Our results showed that AT13148 exerted potent cytotoxic and anti-proliferative activities against a panel human gastric cancer cell lines (HGC-27, AGS, SNU-601, N87 and MKN-28), possibly via inducing cancer cell apoptotic death. Apoptosis inhibition by the Caspase blockers dramatically attenuated AT13148-caused cytotoxicity against gastric cancer cells. Intriguingly, same AT13148 treatment was not cytotoxic/pro-apoptotic to the non cancerous human gastric epithelial GEC-1 cells. At the signaling level, AT13148 treatment in gastric cancer cells dramatically suppressed activation of multiple AGC kinases, including Akt (at p-Thr-308), p70S6 kinase (p70S6K), glycogen synthase kinase 3beta (GSK-3beta) and p90 ribosomal S6 kinase (RSK). Our in vivo studies demonstrated that daily oral gavage of AT13148 at well-tolerated doses significantly inhibited HGC27 xenograft tumor growth in nude mice. AGC activity was also dramatically decreased in AT13148-administrated HGC27 tumors. Therefore, targeting AGC kinases by AT13148 demonstrates superior anti-gastric cancer activity both in vitro and in vivo. The preclinical results of this study support the progression of this molecule into future evaluation as a valuable anti gastric cancer candidate. PMID- 26828268 TI - Disruption of ATP-sensitive potassium channel function in skeletal muscles promotes production and secretion of musclin. AB - Sarcolemmal ATP-sensitive potassium (KATP) channels control skeletal muscle energy use through their ability to adjust membrane excitability and related cell functions in accordance with cellular metabolic status. Mice with disrupted skeletal muscle KATP channels exhibit reduced adipocyte size and increased fatty acid release into the circulation. As yet, the molecular mechanisms underlying this link between skeletal muscle KATP channel function and adipose mobilization have not been established. Here, we demonstrate that skeletal muscle-specific disruption of KATP channel function in transgenic (TG) mice promotes production and secretion of musclin. Musclin is a myokine with high homology to atrial natriuretic peptide (ANP) that enhances ANP signaling by competing for elimination. Augmented musclin production in TG mice is driven by a molecular cascade resulting in enhanced acetylation and nuclear exclusion of the transcription factor forkhead box O1 (FOXO1) - an inhibitor of transcription of the musclin encoding gene. Musclin production/secretion in TG is paired with increased mobilization of fatty acids and a clear trend toward increased circulating ANP, an activator of lipolysis. These data establish KATP channel dependent musclin production as a potential mechanistic link coupling "local" skeletal muscle energy consumption with mobilization of bodily resources from fat. Understanding such mechanisms is an important step toward designing interventions to manage metabolic disorders including those related to excess body fat and associated co-morbidities. PMID- 26828269 TI - The solution structure of the kallikrein-related peptidases inhibitor SPINK6. AB - Kallikrein-related peptidases (KLKs) are crucial for epidermal barrier function and are involved in the proteolytic regulation of the desquamation process. Elevated KLK levels were reported in atopic dermatitis. In skin, the proteolytic activity of KLKs is regulated by specific inhibitors of the serine protease inhibitor of Kazal-type (SPINK) family. SPINK6 was shown to be expressed in human stratum corneum and is able to inhibit several KLKs such as KLK4, -5, -12, -13 and -14. In order to understand the structural traits of the specific inhibition we solved the structure of SPINK6 in solution by NMR-spectroscopy and studied its interaction with KLKs. Thereby, beside the conserved binding mode, we identified an alternate binding mode which has so far not been observed for SPINK inhibitors. PMID- 26828270 TI - A telomerase-derived peptide regulates reactive oxygen species and hepatitis C virus RNA replication in HCV-infected cells via heat shock protein 90. AB - GV1001, a synthetic peptide derived from human telomerase, has a range of diverse biological activities, including an antioxidant function. Here, we investigated the role of GV1001 in hepatitis C virus (HCV)-infected Huh7.5 (JFH-1) cells. We showed that GV1001 inhibited the production of ROS with decreased MAP kinase signaling. Interestingly, GV1001 lost its antioxidant activity as ROS levels decreased, resulting in a reduction in extracellular heat shock protein 90 (eHSP90) as low-density lipoprotein receptor-related protein 1 (LRP1) was blocked or knocked-down. GV1001 binds to eHSP90 and is delivered into the cell by endocytosis via LRP1. Endocytosed GV1001 finally suppressed ROS generation, presumably by hindering the interaction between eHSP90 and NADPH oxidase (NOX). Importantly, GV1001 suppressed HCV RNA replication in JFH-1 cells by inhibiting the binding of HSP90 to FKBP8, a member of the FK506-binding protein family. We also found that HSP90 expression was high in HCV-infected hepatocytes. Therefore, our data suggest that GV1001 may be a good therapeutic agent by controlling HCV RNA replication, as well as by preferentially targeting cells under conditions of oxidative stress. PMID- 26828272 TI - Gamma-glutamylcyclotransferase promotes the growth of human glioma cells by activating Notch-Akt signaling. AB - Glioma as an aggressive type tumor is rapidly growing and has become one of the leading cause of cancer-related death worldwide. gamma-Glutamylcyclotransferase (GGCT) has been shown as a diagnostic marker in various cancers. To reveal whether there is a correlation between GGCT and human glioma, GGCT expression in human glioma tissues and cell lines was first determined. We found that GGCT expression was up-regulated in human glioma tissues and cell lines. Further, we demonstrate that GGCT knockdown inhibits glioma cell T98G and U251 proliferation and colony formation, whereas GGCT overexpression leads to oppose effects. GGCT overexpression promotes the expression of Notch receptors and activates Akt signaling in glioma cells, and Notch-Akt signaling is activated in glioma tissues with high expression of GGCT. Finally, we show that inhibition of Notch-Akt signaling with Notch inhibitor MK-0752 blocks the effects of GGCT on glioma proliferation and colony formation. In conclusion, GGCT plays a critical role in glioma cell proliferation and may be a potential cancer therapeutic target. PMID- 26828271 TI - GSE1 negative regulation by miR-489-5p promotes breast cancer cell proliferation and invasion. AB - Gse1 coiled-coil protein (GSE1), also known as KIAA0182, is a proline rich protein. However, the function of GSE1 is largely unknown. In this study, we reported that GSE1 is overexpression in breast cancer and silencing of GSE1 significantly suppressed breast cancer cells proliferation, migration and invasion. Furthermore, GSE1 was identified as a direct target of miR-489-5p, which is significantly reduced in breast cancer tissues. In addition, forced expression of miR-489-5p suppressed breast cancer cells proliferation, migration and invasion. Moreover, depletion of GSE1 by siRNAs significantly abrogated the enhanced proliferation, migration and invasion of breast cancer cells consequent to miR-489-5p depletion. Taken together, these findings suggest that GSE1 may function as a novel oncogene in breast cancer and it can be regulated by miR-489 5p. PMID- 26828274 TI - The role of polyaluminum chloride in kaolinite aggregation in the sequent coagulation and flocculation process. AB - The role of polyaluminum chloride (PAC) in kaolinite aggregation is studied in this paper by the aggregation of kaolinite with the single and combined use of PAC and polyethylene oxide (PEO). The sequent coagulation and flocculation pattern with the combined use of PAC and PEO shows higher aggregation efficiency than that with the single use of PAC or PEO. In the sequent coagulation and flocculation pattern, the settling velocity and the Zeta potential of kaolinite steadily increase with the PAC concentration, which indicates that the role of PAC is to render the interaction between kaolinite and PEO rather than charge neutralization. This conclusion is supported by the X-ray photoelectron spectroscopy analysis, which shows steady increase of Al-OH group on kaolinite with the PAC concentration. PMID- 26828273 TI - Polyoxometalate-grafted graphene nanohybrid for electrochemical detection of hydrogen peroxide and glucose. AB - The electrochemical performances of electrochemical biosensors largely depend on electrode characteristics, such as size, composition, surface area, and electron and ion conductivities. Herein, highly efficient electrocatalytic polyoxometalate (POM) was directly deposited on polymeric ionic liquid (PIL)-functionalized reduced graphene oxide (rGO) in a simple manner. The nano-sized POM with PIL functional groups was uniformly distributed on the surface of rGO sheets. The unique nanostructure of the resultant POM-g-rGO nanohybrids enabled well-defined multiple redox reaction of POMs and rapid electron transfer. In particular, as prepared nanohybrids demonstrated high electrocatalytic activity for the electrochemical detection of H2O2 and glucose molecules in flow-injection biosensor device with high sensitivity, rapid response time, and low detection limit. PMID- 26828275 TI - A simple way to prepare reduced graphene oxide nanosheets/Fe2O3-Pd/N-doped carbon nanosheets and their application in catalysis. AB - The catalysts with Pd and gamma-Fe2O3 nanoparticles embedded between reduced graphene oxide nanosheets (rGS) and N-doped carbon nanosheets (NCS) were prepared through a two-step method. Firstly, graphene oxide nanosheets (GS)/prussian blue (PB)-Pd/polypyrrole (PPy) composites were synthesized by using pyrrole monomer as reductant, K3Fe(CN)6 and PdCl2 as oxidants in the presence of GS via a redox reaction. Subsequently, the as-obtained GS/PB-Pd/PPy composites were calcinated in N2 atmosphere. During the heat-treatment, carbonization of PPy to NCS, conversion of nonmagnetic PB to magnetic gamma-Fe2O3 nanoparticles, and reduction of GS to rGS were finished, simultaneously. rGS/Fe2O3-Pd/NCS composites exhibited good catalytic activity toward reduction of 4-nitrophenol. The rate constant k and turnover frequency were calculated and compared with recent reports. Owing to gamma-Fe2O3 nanoparticles, the rGS/Fe2O3-Pd/NCS composites could be quickly separated by magnet and reused without obvious decrease in activity. PMID- 26828276 TI - Fabrication of ordered honeycomb amphiphobic films with extremely low fluorine content. AB - A series of poly(methyl methacrylate)-block-poly(perfluoroalkyl ethyl acrylate) (PMMA-b-PFAEA) with various fluorine content were employed to fabricate honeycomb ordered films via breath figure strategy. The influences of temperature, concentration, relative humidity, fluorine content on the morphology of porous films were investigated. Wetting behavior including hydrophobic property and wetting state of the films was studied. High surface roughness from the porous structure and low surface free energy from the increasing PFAEA fraction led to the enhancement of hydrophobicity. Additionally, fabrication of porous films by the mixture of PMMA and PMMA-b-PFAEA was investigated. Ordered porous film with excellent hydrophobicity and oleophobicity was obtained with only 7 wt% of PMMA-b PFAEA by simultaneous processes of breath figure mechanism and phase separation. This work facilitates our further comprehension of the mechanism of breath figure and contributes to the fabrication of porous film from fluorinated copolymers. Meanwhile, it opens a new route to prepare films possessing excellent hydrophobicity and oleophobicity with extremely low fluorine content. PMID- 26828277 TI - Manipulation the properties of supramolecular hydrogels of alpha cyclodextrin/Tyloxapol/carbon-based nanomaterials. AB - Supermolecular hydrogels were prepared by alpha-cyclodeatrin (alpha-CD) and Tyloxapol, which can be considered as an oligomer of the nonionic surfactant polyoxyethylene tert-octylphenyl ether (TX-100) with a polymerization degree below 7. Two carbon materials, graphene oxide (GO) and graphene, were mixed into the alpha-CD/Tyloxapol hydrogel to adjust the physicochemical properties of hydrogel. In order to get stable graphene dispersion and then mix it with alpha CD/Tyloxapol hydrogel, both TX-100 and Tyloxapol were used to disperse graphene for comparison. Interestingly, it can be found that TX-100 could disperse graphene better than Tyloxapol owing to smaller molecular size of TX-100 compared with Tyloxapol. Then, both the alpha-CD/Tyloxapol/GO and alpha CD/Tyloxapol/graphene hydrogels were characterized by transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, small angle X-ray scattering (SAXS), X ray diffraction (XRD) and rheological measurements. The results revealed that the addition of carbon materials into alpha-CD/Tyloxapol hydrogel can change their microstructures and the rheological properties. Furthermore, it can be confirmed that a little amount of carbon materials could induce fluorescence quenching sharply which could be a promising candidate for optical sensor. PMID- 26828278 TI - Control of crystallite and particle size in the synthesis of layered double hydroxides: Macromolecular insights and a complementary modeling tool. AB - Zinc-aluminum layered double hydroxides with nitrate intercalated (Zn(n)Al-NO3, n=Zn/Al) is an intermediate material for the intercalation of different functional molecules used in a wide range of industrial applications. The synthesis of Zn(2)Al-NO3 was investigated considering the time and temperature of hydrothermal treatment. By examining the crystallite size in two different directions, hydrodynamic particle size, morphology, crystal structure and chemical species in solution, it was possible to understand the crystallization and dissolution processes involved in the mechanisms of crystallite and particle growth. In addition, hydrogeochemical modeling rendered insights on the speciation of different metal cations in solution. Therefore, this tool can be a promising solution to model and optimize the synthesis of layered double hydroxide-based materials for industrial applications. PMID- 26828279 TI - Clouding in fatty acid dispersions for charge-dependent dye extraction. AB - The clouding phenomenon in non-ionic surfactant systems is a common feature that remains rare for ionic detergents. Here, we show that fatty acid (negatively charged) systems cloud upon cooling hot dispersions depending on the concentration or when adding excess guanidine hydrochloride. The clouding of these solutions yields the formation of enriched fatty acid droplets in which they exhibit a polymorphism that depends on the temperature: upon cooling, elongated wormlike micelles transit to rigid stacked bilayers inside droplets. Above this transition temperature, droplets coalesce yielding a phase separation between a fatty acid-rich phase and water, allowing extraction of dyes depending on their charge and lipophilicity. Positively charged and zwitterionic dyes were sequestered within the droplets (and then in the fatty acid-rich upper phase) whereas the negatively charged ones were found in both phases. Our results show an additional case of negatively charged surfactant which exhibit clouding phenomenon and suggest that these systems could be used for extracting solutes depending on their charge and lipophilicity. PMID- 26828280 TI - The elusive quest for RNA knots. AB - Physical entanglement, and particularly knots arise spontaneously in equilibrated polymers that are sufficiently long and densely packed. Biopolymers are no exceptions: knots have long been known to occur in proteins as well as in encapsidated viral DNA. The rapidly growing number of RNA structures has recently made it possible to investigate the incidence of physical knots in this type of biomolecule, too. Strikingly, no knots have been found to date in the known RNA structures. In this Point of View Article we discuss the absence of knots in currently available RNAs and consider the reasons why knots in RNA have not yet been found, despite the expectation that they should exist in Nature. We conclude by singling out a number of RNA sequences that, based on the properties of their predicted secondary structures, are good candidates for knotted RNAs. PMID- 26828281 TI - A protocol for the development of reporting criteria for surgical case reports: The SCARE statement. AB - INTRODUCTION: Case reports have specific relevance within the surgical literature. The Case Report Guidelines (CARE) were developed in 2013 to provide a framework to support accuracy in the publication of case reports. As such, they have been adopted by multiple journals. However, they are not tailored to surgery. The objective of this research is to conduct a Delphi consensus exercise amongst experienced case report reviewers and editors to develop the Surgical CAse REport (SCARE) Guidelines. METHODS AND ANALYSIS: The CARE statement will be used as the basis for this Delphi consensus exercise. The Delphi questionnaire will be administered via SurveyMonkey and conducted using standard Delphi Methodology. Surgeons and others with significant experience in reviewing case reports will be invited to participate. There is no pre-determined number of Delphi rounds, although the expectation is that at least three will be needed. Initially, interested parties will be invited to contribute further items for consideration. Then, in each subsequent round, the participants will rate the importance of reporting each outcome on a nine-point Likert scale as proposed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) working group. This process will also be used to agree standard definitions for the outcomes. DISSEMINATION: This work will be disseminated through publication and will be presented at national and international meetings. The findings will be disseminated to interested parties, and journals will be encouraged to endorse the reporting guideline. PMID- 26828282 TI - Increase of calcium and reduction of lactose concentration in milk by treatment with kefir grains and eggshell. AB - Dairy products are the main source of calcium (Ca), but the loss of the consumption habit contributes to low consumption in adulthood, which leads to osteoporosis and increased fracture risk. Domestic use of kefir is straightforward and the eggshell is a natural discarded source of Ca. This paper proposes the development of an enriched Ca reduced lactose milk using eggshell and kefir. During the in vitro preparation, the pH, Ca and lactose contents were measured. Ca intestinal absorption of untreated milk and milk with kefir was compared. Finally, human volunteers consumed this dairy product and 24-h urine Ca was measured. Results showed that the beverage has lower lactose and higher Ca than untreated milk and milk with kefir. Intestinal Ca absorption was not different between both milks and an increase in urinary Ca excretion was observed in humans. This study provides a methodology to prepare at home a dairy product that could contribute to improve the Ca intake in adults. PMID- 26828283 TI - Recent achievements in colorectal cancer diagnostic and therapy by the use of nanoparticles. AB - Colorectal cancer is a major public health issue, being the third most common cancer in men and the second in women. It is one of the leading causes of cancer deaths. Nanomedicine is an emerging field of interest, many of its aspects being linked to cancer research. Chemotherapy has a well-established role in colorectal cancer management, unfortunately being limited by inability to have a selective distribution, by multidrug resistance and adverse effects. Researches carried out in recent years about nanotechnologies aimed, among others, to resolve the issues mentioned above. Targeted and localized delivery of the chemotherapeutic drugs, using nanoparticles, with selective destruction of cancerous cells would minimize the toxicity on healthy tissues. Also, the use of nanomaterials as contrast agent could improve sensitivity and specificity of diagnosis. The purpose of this review is to highlight the recent achievements of cancer research by use of nanomaterials, in the idea of finding the ideal composite, capable to simultaneous diagnostic and treat cancer. PMID- 26828284 TI - The chemical biology of Cu(II) complexes with imidazole or thiazole containing ligands: Synthesis, crystal structures and comparative biological activity. AB - The synthesis and characterization of two copper(II) complexes containing 2-(2 pyridyl)benzimidazole (PyBIm) are reported with the biological activity of these two complexes and a third Cu(II) complex containing 2-(2-pyridyl)benzothiazole (PyBTh). Complex 1, [Cu(PyBIm)(NO3)(H2O)](NO3), is a four coordinate, distorted square planar species with one ligand (N,N), nitrate and water bound to Cu(II). The [Cu(PyBIm)3](BF4)2 complex (2) has distorted octahedral geometry with a 3:1 Py(BIm) ligand to metal ratio. The distorted trigonal bi-pyramidal geometry of compound 3, [Cu(PyBTh)2(H2O)](BF4)2, is comprised of two PyBTh ligands and one water. Biological activity of 1-3 has been assessed by analyzing DNA interaction, nuclease ability, cytotoxic activity and antibacterial properties. Complex 3 exhibits potent concentration dependent SC-DNA cleavage forming single- and double-nicked DNA in contrast to the weak activity of complexes 1 and 2. Mechanistic studies indicate that all complexes utilize an oxidative mechanism however 1 and 2 employ O2(-) as the principal reactive oxygen species while the highly active 3 utilizes (1)O2. The interaction between 1-3 and DNA was investigated using fluorescence emission spectroscopy and revealed all complexes strongly intercalate DNA with Kapp values of 2.65 * 10(6), 1.85 * 10(6) and 2.72 * 10(6)M(-1), respectively. Cytotoxic effects of 1-3 were examined using HeLa and K562 cells and show cell death in the micromolar range with the activity of 1 ~ 2 and were slightly higher than 3. Similar reactivity was observed in the antibacterial studies with E. coli and S. aureus. A detailed comparative analysis of the three complexes is presented. PMID- 26828285 TI - Synthesis, characterization, in vitro cytotoxicity and anticancer effects of ruthenium(II) complexes on BEL-7402 cells. AB - Four new ruthenium(II) polypyridyl complexes [Ru(dmb)2(DQTT)](ClO4)2 (1) (DQTT=12 (1,4-dihydroquinoxalin-6-yl)-4,5,9,14-tetraazabenzo[b]triphenylene, dmb=4,4' dimethyl-2,2'-bipyridine), [Ru(bpy)2(DQTT)](ClO4)2 (2) (bpy=2,2'-bipyridine), [Ru(phen)2(DQTT)](ClO4)2 (3) (phen=1,10-phenanthroline) and [Ru(dmp)2(DQTT)](ClO4)2 (4) (dmp=2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized by elemental analysis, ESI-MS, (1)H NMR and (13)C NMR. The cytotoxic activity in vitro of the complexes was evaluated against human BEL-7402, A549, HeLa, HepG-2 and MG-63 cancer cell lines by MTT (3-(4,5 dimethylthiazole)-2,5-diphenyltetrazolium bromide) method. The IC50 values of complexes 1-4 against BEL-7402 cells are 31.8 +/- 1.0, 35.8 +/- 1.6, 29.0 +/- 0.8 and 25.0 +/- 0.9 MUM, respectively. The morphological apoptosis was investigated with AO/EB (acridine orange/ethidium bromide) and Hoechst 33258 staining methods. The DNA damage was assayed by comet assay. The inhibition of cell migration was evaluated by the wound healing assay. The levels of ROS (reactive oxygen species) and the changes of mitochondrial membrane potential were studied under fluorescent microscope. The percentages in the cells of apoptotic and necrotic cells and the cell cycle arrest were determined by flow cytometry. The expression of Bcl-2 family proteins was investigated by western blot analysis. The results show that the complexes induce BEL-7402 cells apoptosis through a ROS-mediated mitochondrial dysfunction pathway, which was accompanied by regulation of the expression of Bcl-2 family proteins. PMID- 26828286 TI - Adsorption of the cis-[Pt(NH3)2(P2O7)](2-) (phosphaplatin) on hydroxyapatite nanocrystals as a smart way to selectively release activated cis-[Pt(NH3)2Cl2] (cisplatin) in tumor tissues. AB - The relevant adsorption of cis-[Pt(NH3)2(P2O7)](2-) (phosphaplatin) on hydroxyapatite nanocrystals (nHAP) was observed and studied in water suspension. Phosphaplatin cytotoxicity, which is very low for HeLa, MCF-7 and HS-5 cell lines could be enhanced, reaching that of cisplatin, by interaction with solid nHAP. This effect stems from nHAP ability to catalyze the phosphaplatin hydrolysis, producing the same hydrolytic species responsible for cisplatin antitumor activity. PMID- 26828287 TI - Bovine serum albumin binding, antioxidant and anticancer properties of an oxidovanadium(IV) complex with luteolin. AB - Chemotherapy using metal coordination compounds for cancer treatment is the work of the ongoing research. Continuing our research on the improvement of the anticancer activity of natural flavonoids by metal complexation, a coordination compound of the natural antioxidant flavone luteolin (lut) and the oxidovanadium(IV) cation has been synthesized and characterized. Using different physicochemical measurements some structural aspects of [VO(lut)(H2O)2]Na.3H2O (VOlut) were determined. The metal coordinated to two cis-deprotonated oxygen atoms (ArO(-)) of the ligand and two H2O molecules. Magnetic measurements in solid state indicated the presence of an effective exchange pathway between adjacent vanadium ions. VOlut improved the antioxidant capacity of luteolin only against hydroxyl radical. The antitumoral effects were evaluated on MDAMB231 breast cancer and A549 lung cancer cell lines. VOlut exhibited higher viability inhibition (IC50=17 MUM) than the ligand on MDAMB231 cells but they have the same behavior on A549 cells (ca. IC50=60 MUM). At least oxidative stress processes were active during cancer cell-killing. When metals chelated through the carbonyl group and one adjacent OH group of the flavonoid an effective improvement of the biological properties has been observed. In VOlut the different coordination may be the cause of the small improvement of some of the tested properties of the flavonoid. Luteolin and VOlut could be distributed and transported in vivo. Luteolin interacted in the microenvironment of the tryptophan group of the serum binding protein, BSA, by means of electrostatic forces and its complex bind the protein by H bonding and van der Waals interactions. PMID- 26828288 TI - Functionality study of santalin as tyrosinase inhibitor: A potential depigmentation agent. AB - Excessive melanin production leads to hyperpigmentation disorders which results in distressing aesthetic values. Though there are some synthetic depigmentation agents available it has been reported to possess cytotoxic and mutagenic effects. Hence there is a need for the development of safe and non toxic natural tyrosinase inhibitors. Here we report the role of santalin, the chief constituent of Pterocarpus santalinus in inhibition of tyrosinase and melanin synthesis. Santalin inhibited tyrosinase activity dose dependently. Inhibitory kinetic studies revealed mixed type of inhibition with reversible mechanism. Santalin was found to interact with the fluorophore amino acid residue of tyrosinase. Analysis of circular dichroism spectra showed the binding of santalin to tyrosinase which induced the loss of secondary helical structure. Molecular docking result suggested that santalin interact with the catalytic core of tyrosinase through strong hydrogen and hydrophobic bonding. The results of in vitro studies showed santalin inhibited melanogenesis through down regulation of MITF, tyrosinase, TRP 1 and TRP-2 without any cytotoxic effects towards B16F0 melanoma cells. Therefore, our results suggested that santalin possesses anti-tyrosinase activity, which could be utilized as a safe depigmentation agent in the cosmetic field for the treatment of hyperpigmentation disorder. PMID- 26828289 TI - Neuroprotective effect of fucoidan from Turbinaria decurrens in MPTP intoxicated Parkinsonic mice. AB - Fucoidan is one of the dominant sulfated polysaccharide which was extracted from the brown seaweed Turbinaria decurrens. In the behavioral study mice treated with fucoidan showed better response than the MPTP treated mice. Antioxidants and dopamine level has been increased in the fucoidan treated mice when compared to MPTP induced mice. In Immunohistochemistry, the increase of TH positive cells in the fucoidan treated group is correlated with the TH protein levels in substantia nigra and corpus striatum. The increase is greater than the content of dopamine and DOPAC, which may be explained that the dopaminergic terminals are more sensitive to MPTP toxicity and therefore are more severely damaged than the dopaminergic cell bodies. In immunoblotting TH and DAT was used, both the antibodies expression in MPTP was reduced and reversed in other groups. From the results it was conformed that the fucoidan has a neuroprotective effect without any side effects. PMID- 26828290 TI - Evaluation of the Anterior Segment Parameters of the Patients with Scleroderma. AB - PURPOSE: To evaluate corneal parameters of scleroderma (SC) patients by Pentacam HR. METHODS: Twenty-two eyes of 22 SC patients and 33 eyes of 33 control subjects were enrolled. All participants underwent Pentacam (Pentacam-HR, Oculus, Germany) evaluation. Both SC and control groups were divided into two subgroups as dry eye (DE) (Schirmer test with topical anesthesia (STA) ?5 mm) and without DE (STA ?5 mm). RESULTS: Pachymetric measurements and mean corneal volume (CV) were significantly lower in the SC group than in the control group (p<0.001). Pachymetric measurements and CV of SC patients with DE were significantly lower than all the other subgroups. Control subgroups with or without DE were similar in pachymetric measurements and CV. CONCLUSIONS: The results suggest that SC patients have thinner corneas compared with control subjects. Additionally, coexistence of DE seems to have an additional impact in the thinning of cornea in SC patients. PMID- 26828291 TI - The long-run effect of education on obesity in the US. AB - The proportion of obese population has been gradually increasing in the US over the past few decades. In this study I investigate how education is associated with Body Mass Index (BMI) in later stages of life. BMI, weight(kg)/height(m)(2), is the principle measure used for classifying people as obese. Using sibling data and methods that take account of unobserved endowments and environment shared by siblings, I find that there is large variation in BMI between siblings and that education is negatively associated with BMI. One more year of schooling is associated with an estimated reduction of 0.15 in BMI. When considering different education levels, completing college education is associated with 0.7 reduction in BMI relative to high school graduation only. The significant effect of education on obesity that remains in the long-run has policy implications. PMID- 26828292 TI - Time-course and intensity-based classifications of oxidative stresses and their potential application in biomedical, comparative and environmental research. AB - OBJECTIVE: We propose some clues for classification of oxidative stresses based on their intensity and time-course. BACKGROUND: Oxidative stress is studied for more than three decades and it is clear that it may differ on the parameters of interest. But up to now there is no any system for formal discrimination between different types of the stress. Such approach can provide important benefits at description of experimental data. METHOD: We briefly review information on oxidative stresses and show that the theoretical concept is actually poorly developed since introduction of the first definition in 1985 by H. Sies. We argue that the stresses can differ on their intensities and time-curses, but there was no theoretical basis for discrimination between them. RESULTS: On the basis of these analyses, we propose two systems of classifications of oxidative stresses enabling their description taking into account their intensity and time-course. We analyze essential biomarkers of oxidative stress to be used for classification such as levels of modified by reactive oxygen species proteins, lipids, nucleic acids, and low molecular mass compounds. Finally, we describe potential applications of the proposed classifications to biomedical, comparative and environmental research. CONCLUSION: The proposed classifications of oxidative stress may facilitate description of experimental data and their comparison between different organisms and methods of induction of oxidative stresses. Additionally this work may provide some clues to develop quantitative approaches for formal categorization of oxidative stresses. APPLICATION: Most applications of the classifications proposed are theoretical and applied studies where oxidative stress takes place. PMID- 26828293 TI - Population Health: Curriculum Framework for an Emerging Discipline. AB - "Population health" has come to describe an array of initiatives supporting new care and reimbursement models that reward health outcomes rather than volume of services. However, without a standard definition of population health and a comprehensive inventory of the core competencies and knowledge its practitioners must possess, ongoing efforts to address community health outcomes will be hampered. A literature search of peer-reviewed and gray literature, a curriculum scan of current graduate health programs, and an expert panel of industry stakeholders were conducted to develop a comprehensive curriculum framework that broadly defines population health. The result is a concept map consisting of 6 domains--3 knowledge and 3 skills--based-and subcategories. This article discusses the implications for teaching population health and the need for further scholarship to define the field from the point of view of health system leaders, academics, and others who need to hire health professionals with these skills. PMID- 26828294 TI - The palliative efficacy of modified Mohs paste for controlling canine and feline malignant skin wounds. AB - In veterinary medicine, the management of malignant skin wounds is highly challenging. We conducted a study on seven case animals (four dogs and three cats) which presented with malignant skin wounds. All seven animals had signs and symptoms which were controlled following treatment with a modified Mohs paste. Upon obtaining informed consent from their owners, the animals requiring management of malignant wounds were enrolled in this study. The modified Mohs paste was prepared by mixing zinc chloride, zinc oxide starch powder, glycerin, and distilled water. The modified Mohs paste was topically applied to and left to remain on the malignant wounds for one hour, under controlled conditions. Once the paste was removed, the wounds were irrigated with a solution of sterile saline. At the first examination, the wounds of each animal were observed for signs of exudate, malodor, and bleeding. In every case, visible improvement was observed immediately after the modified Mohs paste treatment. Specifically, the size of the malignant wounds, and the number of times the dressing gauze required changing, significantly decreased (p < 0.05 and p < 0.01, respectively). The open malignant skin wounds caused by mammary gland tumors disappeared in two cases. The Mohs paste has been shown to be a viable option for the palliative treatment in canine and feline malignant skin wound management. PMID- 26828295 TI - Editorial: Centennial Celebration-An Interview With Dr Ellis Levin on 100 Years of Estrogens and Health. PMID- 26828298 TI - Polymorphisms in the receptor for advanced glycation end products gene are associated with susceptibility to drug-resistant epilepsy. AB - Increasing evidence has demonstrated that inflammation plays an important role in epilepsy (EP). As a cell-surface molecule of the immunoglobulin superfamily, the receptor for advanced glycation end products (RAGE) is involved in inflammation related disease. Functional polymorphisms in the regulatory elements and/or ligand-binding regions of RAGE may alter the expression and function of RAGE, thus affecting EP susceptibility. Here, we have identified a novel association between genetic variants in the RAGE G82S locus and EP (p=0.033) using a case control study in a Chinese population. Further analyses showed that the 82S+ genotype and S allele were more common in patients with drug-resistant epilepsy (DRE) than in those with drug-responsive EP compared with controls. The loci 374T/A and -429T/C did not demonstrate any association with EP, but the haplotype T-A-A exhibited significantly different frequencies between DRE patients and controls (OR=1.696, 95% CI: 1.188-2.420, P=0.003). Our study provides preliminary evidence that the G82S polymorphism in RAGE is associated with increased DRE risk and that the GS genotype of the G82S locus is a risk factor for DRE in the Chinese population. PMID- 26828299 TI - Ventral tegmental area muscarinic receptors modulate depression and anxiety related behaviors in rats. AB - Cholinergic and dopaminergic mechanisms within the mesolimbic dopamine system are suggested to play a role in the manifestation of depression and anxiety-related disorders. However, despite the fact that cholinergic mechanisms in the ventral tegmental area (VTA) highly regulate dopamine activity, the role of VTA cholinergic mechanisms in depression-related behaviors is relatively unknown. Here we sought to determine whether enhancing cholinergic tone in the VTA would alter depression and anxiety-related behavior in the forced swim test (FST), elevated plus maze (EPM) and sucrose preference test (SPT). Adult Sprague Dawley male rats received VTA infusion of the acetylcholinesterase inhibitor, physostigmine (0, 1, 2MUg/side), immediately prior to the FST, EPM, or SPT. Physostigmine administration increased immobility time in the FST, decreased time spent on open arms in the EPM, and decreased sucrose preference. We also examined whether activation of VTA muscarinic receptors was sufficient to alter behavior in the FST and EPM. Similar to physostigmine, VTA infusion of the muscarinic receptor agonist, pilocarpine (0, 3, 30MUg/side), increased immobility time in the FST and decreased time spent on open arms in the EPM. These data suggest that enhanced VTA cholinergic tone promotes pro-depressive and anxiogenic-like effects and demonstrate that specific activation of VTA muscarinic receptors is also sufficient to induce pro-depressive and anxiogenic responses. Together, these findings reveal a novel role of VTA cholinergic, and specifically muscarinic receptor, mechanisms in mediating responses to stress and anxiety. PMID- 26828300 TI - Study of breakthrough cancer pain in an animal model induced by endothelin-1. AB - Cancer patients with bone metastases often suffer breakthrough pain. However, little progress has been made in the treatment of breakthrough pain and its associated mechanism(s) in the patient with cancer due to lacking of resembling and predictive animal models. We previously have demonstrated that endothelin-1 plays an important role in breakthrough cancer pain. In the present study, we have established an animal model of breakthrough cancer pain induced by endothelin-1. The animal model of breakthrough cancer pain is strictly followed the definition and meets the characteristics of breakthrough pain. The model is reliable, reproducible and easy to be produced. To our knowledge, this is the first report for establishing such an animal model. In addition, we also found that a selective ETA receptor antagonist BQ-123 could reverse endothelin-1 induced breakthrough pain. We further studied the characteristics of pain behaviors such as hind limb use score and voluntary wheel running as well as the electrophysiology of sciatic nerve fibers with the model. The murine model shows high resemblance compared to the breakthrough cancer pain in the patients with cancer clinically. It provides a platform for further study of the pathogenesis of breakthrough cancer pain and targeted intervention. PMID- 26828301 TI - Clonidine as an adjuvant for propranolol enhances its effect on infiltrative cutaneous analgesia in rats. AB - Clonidine prolongs duration of analgesia when used as an adjunct to local anesthetics for infiltrative cutaneous analgesia, and propranolol produces local anesthesia. The purpose of the experiment was to evaluate clonidine as an adjuvant for propranolol on the quality and duration of cutaneous analgesia. A rat model of cutaneous trunci muscle reflex (CTMR) in response to local skin pinprick was employed to evaluate the cutaneous analgesic effect of propranolol combined with clonidine. The long-lasting local anesthetic bupivacaine was used as control. Cutaneous analgesia elicited by propranolol and bupivacaine was dose dependent, and both propranolol (9.0MUmol) and bupivacaine (1.8MUmol) produced 100% nociceptive blockade. On an 50% effective dose (ED50) basis, the relative potency was bupivacaine [0.48 (0.42-0.55) MUmol] greater than propranolol [2.27 (1.98-2.54) MUmol] (p<0.01). Subcutaneous saline and clonidine (0.12MUmol) did not produce cutaneous analgesia. The mixture of an ineffective-dose clonidine (0.12MUmol) and a drug (propranolol or bupivacaine) at ED50 or ED95 increased the potency and extended the duration at producing cutaneous analgesia. The resulting data demonstrated that propranolol is less potent than bupivacaine as an infiltrative anesthetic. Clonidine as an adjuvant for propranolol or bupivacaine has a significant peripheral action in increasing the depth and duration of action on infiltrative cutaneous analgesia. PMID- 26828302 TI - Socioeconomic status is associated with striatal dopamine D2/D3 receptors in healthy volunteers but not in cocaine abusers. AB - Positron emission tomography (PET) studies in animals and humans have shown that social status is associated with striatal dopamine D2/D3 receptor (D2/D3R) availability. That is, higher social hierarchy and higher scores on questionnaires assessing social status correlated positively with striatal D2/D3R availability in animals and humans respectively. Furthermore, subordinate monkeys were vulnerable to cocaine self-administration, suggesting that alternations in social hierarchy can change D2/D3R availability and vulnerability to cocaine use. Here, we investigated whether socioeconomic status (SES) measured with the Hollingshead scale is associated with striatal D2D/3R availability using [(11)C]raclopride PET in 38 cocaine abusers and 42 healthy controls matched for age and education. Compared to controls, cocaine abusers showed lower D2/D3R availability in the caudate, putamen and ventral striatum (all p<=0.001). Despite matching groups for education, SES scores were lower in cocaine abusers than controls (p<0.001). In the control group only, SES scores significantly correlated with D2/D3R in caudate (r=0.35, p=0.024) and putamen (r=0.39, p=0.011) but not in ventral striatum (p=0.61); all corrected for age. The study confirms that SES is associated with striatal D2/D3R availability in healthy human volunteers. However, reductions in D2/D3R availability in cocaine abusers may be driven by factors other than SES such as chronic cocaine exposure. PMID- 26828303 TI - Meta-analysis of BACE1 gene rs638405 polymorphism and the risk of Alzheimer's disease in Caucasion and Asian population. AB - Recent studies showed the beta-site amyloid precursor protein cleaving enzyme (BACE) is associated with Alzheimer's disease (AD). However, studies investigating the association of single-nucleotide polymorphism (SNP) in exon 5 of BACE1 (rs638405, C786G, Val262) with AD are controversial. Therefore we conducted this meta-analysis to clarify the association. Relevant studies were identified on PubMed, Cochrane library and CNKI from established through July 2015 according to the inclusion criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) and five genetic models were applied to assess the association. A total of 13 studies composed of 2538 AD patients and 3020 controls were included in this study. Significant association of SNP rs638405 with AD was found in overall population among allelic genetic model (G vs. C: OR=1.11, 95%CI=1.02 1.20, P=0.01), codominant genetic model (GG vs. CC: OR=1.22, 95%CI=1.04-1.44, P=0.02) and recessive genetic model (GG vs. GC+ CC: OR=1.25, 95%CI=1.10-1.42, P=0.0008). Besides, subgroup analysis indicated significant association among Asian population (allelic genetic model, G vs. C, OR=1.18, 95%CI=1.04-1.34, P=0.01; codominant genetic model, GG vs. CC, OR=1.43, 95%CI=1.08-1.89, P=0.01 and recessive genetic model, GG vs. GC+ CC, OR=1.40, 95%CI=1.09-1.78, P=0.008) and Caucasion population (recessive genetic model, GG vs. GC+ CC, OR=1.20, 95%CI=1.02 1.39, P=0.02). Our analysis demonstrated that GG genotype and G allele of BACE1 gene rs638405 probably increase the risk of AD. PMID- 26828304 TI - The inhibitory effect of propofol on Kv2.1 potassium channel in rat parietal cortical neurons. AB - Excessive K(+) efflux via activated voltage-gated K(+) channels can deplete intracellular K(+) and lead to long-lasting membrane depolarization which will promote neuronal apoptosis during ischemia/hypoxia injury. The Kv2.1 potassium channel was the major component of delayed rectifier potassium current (Ik) in pyramidal neurons in cortex and hippocampus. The neuronal protective effect of propofol has been proved. Delayed rectifier potassium current (Ik) has been shown to have close relationship with neuronal damage. The study was designed to test the inhibitory effect of propofol on Kv2.1 potassium channel in rat parietal cortical neurons. Whole-cell patch clamp recordings and Western blot analysis were used to investigate the electrophysiological function and protein expression of Kv2.1 in rat parietal cortical neurons after propofol treatment. We found that propofol concentration-dependently inhibited Ik in pyramidal neurons. Propofol also caused a downward shift of the I-V curve of Ik at 30MUM concentration. Propofol significantly inhibited the expression of Kv2.1 protein level at 30MUM, 50MUM, 100MUM concentration. In conclusion, our data showed that propofol could inhibit Ik, probably via depressing the expression of Kv2.1 protein in rat cerebral parietal cortical neurons. PMID- 26828305 TI - Pharmacologic Management Strategies in ALS #301. PMID- 26828306 TI - Nature, Strength, and Cooperativity of the Hydrogen-Bonding Network in alpha Chitin. AB - Chitin is an abundant biopolymer that stabilizes the exoskeleton of insects and gives structure to plants. Its macroscopic properties go back to an intricate network of hydrogen bonds that connect the polymer strands, and these intermolecular links have been under ongoing study. Here, we use atomistic simulations to explore hydrogen bonding in the most abundant form, alpha-chitin. The crystal structure exhibits disorder, and so discrete models are systematically derived as suitable approximants to the macroscopic material. These models then allow us to perform dispersion-corrected density-functional theory (DFT-D) simulations on the three-dimensional crystal network and on lower dimensional fragments. Thereby, we rationalize the nature of hydrogen bonding and the role of crystallographic disorder for the stability of alpha-chitin, and complement previous, larger-scale molecular-dynamics (MD) simulations as well as recent fiber-diffraction experiments. Our results provide new, atomic-level insight into one of Nature's most abundant building materials, and the techniques and concepts are likely transferable to other biopolymers. PMID- 26828307 TI - Divergent Syntheses of Isoquinolines and Indolo[1,2-a]quinazolines by Copper Catalyzed Cascade Annulation from 2-Haloaryloxime Acetates with Active Methylene Compounds and Indoles. AB - A convenient and reliable method for the direct construction of isoquinolines is described. A series of isoquinoline derivatives were synthesized, with high chemo and regioselectivities, via the copper-catalyzed cascade reaction of 2 haloaryloxime acetates with beta-diketones, beta-keto esters, and beta-keto nitriles. This tandem annulation process features inexpensive catalysts, no need for additional ligands, and excellent functional group tolerance, which makes it have potential synthetic applications. Furthermore, this strategy could also be used to enter functionalized indolo[1,2-a]quinazolines by using indoles as the counterpart of the 2-haloaryloxime acetates. PMID- 26828308 TI - Bottom-Up Nanofabrication of Supported Noble Metal Alloy Nanoparticle Arrays for Plasmonics. AB - Mixing different elements at the nanoscale to obtain alloy nanostructures with fine-tuned physical and chemical properties offers appealing opportunities for nanotechnology and nanoscience. However, despite widespread successful application of alloy nanoparticles made by colloidal synthesis in heterogeneous catalysis, nanoalloy systems have been used very rarely in solid-state devices and nanoplasmonics-related applications. One reason is that such applications require integration in arrays on a surface with compelling demands on nanoparticle arrangement, uniformity in surface coverage, and optimization of the surface density. These cannot be fulfilled even using state-of-the-art self assembly strategies of colloids. As a solution, we present here a generic bottom up nanolithography-compatible fabrication approach for large-area arrays of alloy nanoparticles on surfaces. To illustrate the concept, we focus on Au-based binary and ternary alloy systems with Ag, Cu, and Pd, due to their high relevance for nanoplasmonics and complete miscibility, and characterize their optical properties. Moreover, as an example for the relevance of the obtained materials for integration in devices, we demonstrate the superior and hysteresis-free plasmonic hydrogen-sensing performance of the AuPd alloy nanoparticle system. PMID- 26828309 TI - Size and Surface Charge of Engineered Poly(amidoamine) Dendrimers Modulate Tumor Accumulation and Penetration: A Model Study Using Multicellular Tumor Spheroids. AB - An enormous effort has been put into designing nanoparticles (NPs) with controlled biodistributions, prolonged plasma circulation times, and/or enhanced tissue targeting. However, little is known about how to design NPs with precise distributions in the target tissues. In particular, understanding NP tumor penetration and accumulation characteristics is crucial to maximizing the therapeutic potential of drug molecules carried by the NPs. In this study, we employed poly(amidoamine) (PAMAM) dendrimers, given their well-controlled size (<10 nm) and surface charge, to understand how the physical properties of NPs govern their tumor accumulation and penetration behaviors. We demonstrate for the first time that the size and surface charge of PAMAM dendrimers control their distributions in both a 3D multicellular tumor spheroid (MCTS) model and a separate extracellular matrix (ECM) model, which mimics the tumor microenvironment. Smaller PAMAM dendrimers not only diffused more rapidly in the ECM model but also efficiently penetrated to the MCTS core compared to their larger counterparts. Furthermore, cationic, amine-terminated PAMAM dendrimers exhibited the greatest accumulation in MCTS compared to either charge-neutral or anionic dendrimers. Our findings indicate that the size and surface charge of PAMAM dendrimers may tailor their tumor accumulation and penetration behaviors. These results suggest that controlled tumor accumulation and distinct intratumoral distributions can be achieved by simply controlling the size and surface charge of dendrimers, which may also be applicable for other similarly sized NPs. PMID- 26828310 TI - Isoxazole Alters Metabolites and Gene Expression, Decreasing Proliferation and Promoting a Neuroendocrine Phenotype in beta-Cells. AB - Novel strategies are needed to modulate beta-cell differentiation and function as potential beta-cell replacement or restorative therapies for diabetes. We previously demonstrated that small molecules based on the isoxazole scaffold drive neuroendocrine phenotypes. The nature of the effects of isoxazole compounds on beta-cells was incompletely defined. We find that isoxazole induces genes that support neuroendocrine and beta-cell phenotypes and suppresses genes important for proliferation. Isoxazole alters beta-cell metabolites and protects glucose responsive signaling pathways under lipotoxic conditions. Finally, we show that isoxazole improves glycemia in a mouse model of beta-cell regeneration. Isoxazole is a prime candidate to alter cell fate in different contexts. PMID- 26828311 TI - The Interfacial Behavior between Biochar and Soil Minerals and Its Effect on Biochar Stability. AB - In this study, FeCl3, AlCl3, CaCl2, and kaolinite were selected as model soil minerals and incubated with walnut shell derived biochar for 3 months and the incubated biochar was then separated for the investigation of biochar-mineral interfacial behavior using XRD and SEM-EDS. The XPS, TGA, and H2O2 oxidation were applied to evaluate effects of the interaction on the stability of biochar. Fe8O8(OH)8Cl1.35 and AlCl3.6H2O were newly formed on the biochar surface or inside of the biochar pores. At the biochar-mineral interface, organometallic complexes such as Fe-O-C were generated. All the 4 minerals enhanced the oxidation resistance of biochar surface by decreasing the relative contents of C O, C?O, and COOH from 36.3% to 16.6-26.5%. Oxidation resistance of entire biochar particles was greatly increased with C losses in H2O2 oxidation decreasing by 13.4-79.6%, and the C recalcitrance index (R50,bicohar) in TGA analysis increasing from 44.6% to 45.9-49.6%. Enhanced oxidation resistance of biochar surface was likely due to the physical isolation from newly formed minerals, while organometallic complex formation was probably responsible for the increase in oxidation resistance of entire biochar particles. Results indicated that mineral-rich soils seemed to be a beneficial environment for biochar since soil minerals could increase biochar stability, which displays an important environmental significance of biochar for long-term carbon sequestration. PMID- 26828312 TI - Toward Contactless Biology: Acoustophoretic DNA Transfection. AB - Acoustophoresis revolutionized the field of container-less manipulation of liquids and solids by enabling mixing procedures which avoid contamination and loss of reagents due to the contact with the support. While its applications to chemistry and engineering are straightforward, additional developments are needed to obtain reliable biological protocols in a contactless environment. Here, we provide a first, fundamental step towards biological reactions in air by demonstrating the acoustophoretic DNA transfection of mammalian cells. We developed an original acoustophoretic design capable of levitating, moving and mixing biological suspensions of living mammalians cells and of DNA plasmids. The precise and sequential delivery of the mixed solutions into tissue culture plates is actuated by a novel mechanism based on the controlled actuation of the acoustophoretic force. The viability of the contactless procedure is tested using a cellular model sensitive to small perturbation of neuronal differentiation pathways. Additionally, the efficiency of the transfection procedure is compared to standard, container-based methods for both single and double DNA transfection and for different cell types including adherent growing HeLa cancer cells, and low adhesion neuron-like PC12 cells. In all, this work provides a proof of principle which paves the way to the development of high-throughput acoustophoretic biological reactors. PMID- 26828313 TI - Realistic molecular model of kerogen's nanostructure. AB - Despite kerogen's importance as the organic backbone for hydrocarbon production from source rocks such as gas shale, the interplay between kerogen's chemistry, morphology and mechanics remains unexplored. As the environmental impact of shale gas rises, identifying functional relations between its geochemical, transport, elastic and fracture properties from realistic molecular models of kerogens becomes all the more important. Here, by using a hybrid experimental-simulation method, we propose a panel of realistic molecular models of mature and immature kerogens that provide a detailed picture of kerogen's nanostructure without considering the presence of clays and other minerals in shales. We probe the models' strengths and limitations, and show that they predict essential features amenable to experimental validation, including pore distribution, vibrational density of states and stiffness. We also show that kerogen's maturation, which manifests itself as an increase in the sp(2)/sp(3) hybridization ratio, entails a crossover from plastic-to-brittle rupture mechanisms. PMID- 26828314 TI - Approaching theoretical strength in glassy carbon nanolattices. AB - The strength of lightweight mechanical metamaterials, which aim to exploit material-strengthening size effects by their microscale lattice structure, has been limited by the resolution of three-dimensional lithography technologies and their restriction to mainly polymer resins. Here, we demonstrate that pyrolysis of polymeric microlattices can overcome these limitations and create ultra-strong glassy carbon nanolattices with single struts shorter than 1 MUm and diameters as small as 200 nm. They represent the smallest lattice structures yet produced- achieved by an 80% shrinkage of the polymer during pyrolysis--and exhibit material strengths of up to 3 GPa, corresponding approximately to the theoretical strength of glassy carbon. The strength-to-density ratios of the nanolattices are six times higher than those of reported microlattices. With a honeycomb topology, effective strengths of 1.2 GPa at 0.6 g cm(-3) are achieved. Diamond is the only bulk material with a notably higher strength-to-density ratio. PMID- 26828315 TI - Conductance saturation in a series of highly transmitting molecular junctions. AB - Revealing the mechanisms of electronic transport through metal-molecule interfaces is of central importance for a variety of molecule-based devices. A key method for understanding these mechanisms is based on the study of conductance versus molecule length in molecular junctions. However, previous works focused on transport governed either by coherent tunnelling or hopping, both at low conductance. Here, we study the upper limit of conductance across metal-molecule-metal interfaces. Using highly conducting single-molecule junctions based on oligoacenes with increasing length, we find that the conductance saturates at an upper limit where it is independent of molecule length. With the aid of two prototype systems, in which the molecules are contacted by either Ag or Pt electrodes, we find two different possible origins for conductance saturation. The results are explained by an intuitive model, backed by ab initio calculations. Our findings shed light on the mechanisms that constrain the conductance of metal-molecule interfaces at the high-transmission limit. PMID- 26828316 TI - Organically linked iron oxide nanoparticle supercrystals with exceptional isotropic mechanical properties. AB - It is commonly accepted that the combination of the anisotropic shape and nanoscale dimensions of the mineral constituents of natural biological composites underlies their superior mechanical properties when compared to those of their rather weak mineral and organic constituents. Here, we show that the self assembly of nearly spherical iron oxide nanoparticles in supercrystals linked together by a thermally induced crosslinking reaction of oleic acid molecules leads to a nanocomposite with exceptional bending modulus of 114 GPa, hardness of up to 4 GPa and strength of up to 630 MPa. By using a nanomechanical model, we determined that these exceptional mechanical properties are dominated by the covalent backbone of the linked organic molecules. Because oleic acid has been broadly used as nanoparticle ligand, our crosslinking approach should be applicable to a large variety of nanoparticle systems. PMID- 26828317 TI - Engaging Alkenyl Halides with Alkylsilicates via Photoredox Dual Catalysis. AB - Single-electron transmetalation via photoredox/nickel dual catalysis provides the opportunity for the construction of Csp(3)-Csp(2) bonds through the transfer of alkyl radicals under very mild reaction conditions. A general procedure for the cross-coupling of primary and secondary (bis-catecholato)alkylsilicates with alkenyl halides is presented. The developed method allows not only alkenyl bromides and iodides but also previously underexplored alkenyl chlorides to be employed. PMID- 26828318 TI - Volatile organic compounds discriminate between eosinophilic and neutrophilic inflammation in vitro. AB - Inflammation associated oxidative stress leads to peroxidation of polyunsaturated fatty acids thereby generating volatile organic compounds (VOCs). The integrative analysis of the total amount of VOCs released by eosinophils and neutrophils in vitro enables the search for those compounds that discriminates between various inflammatory conditions. The approach comprises isolating eosinophils and neutrophils from 30 ml of blood of healthy non-smoking volunteers by gradient centrifugation, using lymphoprep. Eosinophils are separated from neutrophils by immunomagnetic cell separation using anti-CD16. Cells are activated with phorbol 12-myristate 13-acetate and VOCs from the headspace are collected at time 0', 30', 60' and 90' by introduction of ultra-pure nitrogen in the closed flasks at a flow rate of 200 ml min(-1) during 10 min. The gases are trapped onto a sorption tube and analyzed by gas chromatography-time-of-flight-mass spectometry (GC-TOF MS) in order to identify VOCs released in the headspace by activated neutrophils and eosinophils. Eosinophils and neutrophils were isolated from 26 healthy non smoking volunteers. The average absolute number of eosinophils and neutrophils upon isolation was 3.5 * 10(6) and 19.4 * 10(6), respectively. The volatome in headspace consisted of 2116 compounds and those compounds present in at least 8% of the samples (1123 compounds) were used for further discriminant analysis. Discriminant analysis showed that two VOCs were able to distinguish between eosinophilic and neutrophilic cultures in the unactivated state with 100% correct classification of the entire data set and upon cross validation while five VOCs were able to discriminate between activated eosinophils and neutrophils with 96% correct classification in the original set and upon cross-validation. Analysis of VOCs seems to be a very promising approach in identifying eosinophilic and neutrophilic inflammation but it needs further development and in vivo confirmation. PMID- 26828319 TI - Mean Age of Mothers is on the Rise: United States, 2000-2014. AB - KEY FINDINGS: Data from the National Vital Statistics System. The mean age of mothers has increased from 2000 to 2014 for all birth orders, with age at first birth having the largest increase, up from 24.9 years in 2000 to 26.3 years in 2014. Increases in the average age for all birth orders were most pronounced from 2009 to 2014. In 2014, Asian or Pacific Islander mothers had the oldest average age at first birth (29.5 years), while American Indian or Alaska Native mothers had the youngest (23.1 years). Mean age at first birth increased in all states and the District of Columbia (D.C.) from 2000 to 2014, but D.C. (3.4 years) and Oregon had the largest increases (2.1 years). PMID- 26828321 TI - Apolipoprotein A-I Mimetic Peptide D-4F Reduces Cardiac Hypertrophy and Improves Apolipoprotein A-I-Mediated Reverse Cholesterol Transport From Cardiac Tissue in LDL Receptor-null Mice Fed a Western Diet. AB - Epidemiological studies have suggested that hypercholesterolemia is an independent determinant of increased left ventricular (LV) mass. Because high density lipoprotein and its major protein apolipoprotein A-I (apoA-I) mediate reverse cholesterol transport (RCT) and have cardiac protective effects, we hypothesized that the apoA-I mimetic peptide D-4F could promote RCT in cardiac tissue and decrease cardiac hypertrophy induced by hypercholesterolemia. Low density lipoprotein receptor-null mice were fed by a Western diet for 18 weeks and then randomized to receive water, or D-4F 0.3 mg/mL, or D-4F 0.5 mg/mL added to drinking water for 6 weeks. After D-4F administration, an increase in high density lipoprotein cholesterol and a decrease in low-density lipoprotein cholesterol, total cholesterol, and triglyceride in a trend toward dose responsivity were found in cardiac tissue. Ultrasound biomicroscopy revealed a reduction in LV posterior wall end-diastolic dimension, and an increase in mitral valve E/A ratio and LV ejection fraction. Hematoxylin-eosin staining showed reduced LV wall thickness and myocardial cell diameter. The protein levels of ABCA1 and LXRalpha were elevated in cardiac tissue of D-4F treated mice compared with the controls (P < 0.05). These results demonstrated that D-4F treatment reduced cardiac hypertrophy, and improved cardiac performance in low-density lipoprotein receptor-null mice fed a Western diet, presumably through the LXRalpha-ABCA1 pathway associated with enhanced myocardial RCT. PMID- 26828322 TI - Helix B Surface Peptide Protects Cardiomyocytes Against Hypoxia/Reoxygenation induced Apoptosis Through Mitochondrial Pathways. AB - BACKGROUND: Helix B surface peptide (HBSP), a newly developed tissue-protective erythropoietin derivative, has beneficial effects on myocardial ischemia. This study aimed to investigate the cardio-protective effects of HBSP against hypoxia/reoxygenation (H/R) injury and its possible mechanism. METHODS: A rat derived cardiomyocyte cell line (H9C2 cells) were established and pretreated with HBSP. The pretreated primary cultures were subjected to H/R and monitored for cell viability using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Intracellular reactive oxygen species (ROS) levels, apoptosis, and mitochondrial membrane potential (DeltaPsim) were detected by flow cytometry. The expression of cytochrome C and Bcl-2 family proteins, as well as the activities of caspases 3 and 9 were determined by Western blot analysis and a colorimetric method, respectively. RESULTS: HBSP reduced apoptotic cells in cardiomyocytes subjected to H/R. In HBSP-treated cardiomyocytes, the H/R-induced mitochondrial ROS production, DeltaPsim collapse, and cytochrome C release from mitochondria to the cytosol significantly decreased. Moreover, HBSP inhibited the activation of caspases 9 and 3, as well as the alteration of Bcl-2 family proteins, which were induced by H/R. CONCLUSIONS: These results indicated that HBSP has protective effects against H/R-induced apoptosis by regulating the mitochondrial pathway. This mechanism involves inhibiting mitochondrial ROS generation, inhibiting caspase-3 activity, reducing DeltaPsim collapse, reducing cytochrome release, and balancing anti and proapoptotic Bcl-2 family proteins. PMID- 26828323 TI - Role of Monokine Induced by Interferon Gamma in Discrimination and Prognosis of Patients With Chagas' Disease and Idiopathic Dilated Cardiomyopathy. AB - AIMS: Monokine induced by interferon gamma (MIG) is a chemokine that has been found to increase in the myocardium of mice infected with Trypanosoma cruzi. It is not known whether MIG is regulated in patients with Chagas' disease (CD) and idiopathic dilated cardiomyopathy (DCM). Therefore, we aimed to investigate the possible diagnostic and/or prognostic value of MIG in these patients. METHODS AND RESULTS: In this prospective cohort study, MIG was measured in patients with CD (n = 93) and DCM (n = 47) and in healthy control subjects (n = 24). MIG was found to be significantly increased in patients with CD and advanced heart failure (New York Heart Association III-IV). Although no significant increase in MIG levels was observed in patients with DCM, there was a significant correlation between MIG and left ventricular ejection fraction in patients with DCM. In contrast, despite the significant increase in patients with CD and advanced heart failure, MIG had no significant correlation with any of the echocardiographic parameters in CD. MIG also failed to predict mortality and necessity for heart transplant in patients with CD but showed a clear trend for patients with DCM. CONCLUSIONS: To the best of our knowledge, this is the first study to investigate MIG in patients with CD and DCM. The significant increase of MIG in patients with CD and advanced heart failure, the negative correlation between MIG and left ventricular ejection fraction, and the clear trend in discrimination using a cutoff value found in patients with DCM require further investigation to clarify the diagnostic and prognostic potential of MIG in these patients. PMID- 26828325 TI - Synthesis of strigolactones, a strategic account. PMID- 26828324 TI - Safety and Tolerability of High-dose Inhaled Treprostinil in Pulmonary Hypertension. AB - Pulmonary arterial hypertension (PAH) has emerging therapeutic options including prostacyclin analogs. Inhaled therapy offers advantages compared with alternative routes of administration. We aimed to determine the safety and tolerability of inhaled treprostinil (iTRE) titrated to target maintenance dose higher than the labeled dose for PAH. Our study included 80 consecutive patients (69% female, 70% White) followed at the Duke University Medical Center prescribed iTRE at dose >9 breaths (54 MUg). Etiology of pulmonary hypertension was most frequently PAH (51%) or secondary to lung disease (35%). Median follow-up was 20.3 months (interquartile range 14.2-33.2). Most patients (91%) had titrated iTRE dose to 12 breaths (72 MUg) four times daily. Common side effects reported with drug initiation were cough (41%), headache (28%), and throat irritation (8%); most of the side effects improved at follow-up. Overall, 25% patients discontinued iTRE: 9 transitioned to parenteral therapy, 4 had untolerable side effects, 3 died, and 4 had other reasons. Overall, iTRE taken at a higher dose than approved for use in PAH was safe and well-tolerated in our cohort of pulmonary hypertension patients. PMID- 26828327 TI - Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction 2016 Winter Meeting February 23-27, 2016 The Roosevelt New Orleans, A Waldorf Astoria Hotel New Orleans, Louisiana. PMID- 26828326 TI - Editorial Comment. PMID- 26828328 TI - A Simple Light Stimulation of Caenorhabditis elegans. AB - Response via noxious stimulus can be an important indicator of sensory neuron function and overall health of an organism. If the stimulation is quick and simple, and the animal can be rescued afterwards, such a method not only allows for assays pertaining to changed sensory ability after various treatments, but also increases the reliability of the statistical relationships that are established. This protocol demonstrates a stimulation assay in Caenorhabditis elegans, using blue light from common laboratory equipment: the fluorescent microscope. The nematode detects blue light using a set of amphid ciliary sensory neurons, and blue light is detrimental to its overall health after a prolonged exposure. However, under brief exposure, blue light stimulation provides a rapid and easy method for quantifying sensory functions and health without harming the animal. PMID- 26828331 TI - Evaluation of Toxicity in Mouse Bone Marrow Progenitor Cells. AB - Development of blood cells through hematopoiesis occurs in the bone marrow (BM), and can be adversely impacted by various substances and/or conditions ranging from known therapeutic, intentionally administered xenobiotics to unintentional food additives and exposure to environmental chemicals. The principles underlying the techniques for evaluating toxicity to BM progenitors (erythroid, myeloid, and lymphoid) exploit changes in the normal hematopoietic process, biochemical cell surface and intracellular markers, as well as components of the BM microenvironment. Toxicological investigations following in vivo exposures of mice or in vitro exposures of mouse primary BM cell cultures allow the assessment of the developmental and functional integrity of BM cells, cell population shifts, and adverse biochemical effects due to toxicity. Colony forming unit (CFU) assays and flow cytometry are indispensable techniques in these toxicity studies. PMID- 26828329 TI - The Use of Induced Pluripotent Stem Cells for the Study and Treatment of Liver Diseases. AB - Liver disease is a major global health concern. Liver cirrhosis is one of the leading causes of death in the world and currently the only therapeutic option for end-stage liver disease (e.g., acute liver failure, cirrhosis, chronic hepatitis, cholestatic diseases, metabolic diseases, and malignant neoplasms) is orthotropic liver transplantation. Transplantation of hepatocytes has been proposed and used as an alternative to whole organ transplant to stabilize and prolong the lives of patients in some clinical cases. Although these experimental therapies have demonstrated promising and beneficial results, their routine use remains a challenge due to the shortage of donor livers available for cell isolation, variable quality of those tissues, the potential need for lifelong immunosuppression in the transplant recipient, and high costs. Therefore, new therapeutic strategies and more reliable clinical treatments are urgently needed. Recent and continuous technological advances in the development of stem cells suggest they may be beneficial in this respect. In this review, we summarize the history of stem cell and induced pluripotent stem cell (iPSC) technology in the context of hepatic differentiation and discuss the potential applications the technology may offer for human liver disease modeling and treatment. This includes developing safer drugs and cell-based therapies to improve the outcomes of patients with currently incurable health illnesses. We also review promising advances in other disease areas to highlight how the stem cell technology could be applied to liver diseases in the future. (c) 2016 by John Wiley & Sons, Inc. PMID- 26828330 TI - Associating Changes in the Immune System with Clinical Diseases for Interpretation in Risk Assessment. AB - This overview is an update of the unit originally published in 2004. While the basic tenets of immunotoxicity have not changed in the past 10 years, several publications have explored the application of immunotoxicological data to the risk assessment process. Therefore, the goal of this unit is still to highlight relationships between xenobiotic-induced immunosuppression and risk of clinical diseases progression. In immunotoxicology, this may require development of models to equate moderate changes in markers of immune functions to potential changes in incidence or severity of infectious diseases. For most xenobiotics, exposure levels and disease incidence data are rarely available, and safe exposure levels must be estimated based on observations from experimental models or human biomarker studies. Thus, it is important to establish a scientifically sound framework that allows accurate and quantitative interpretation of experimental or biomarker data in the risk assessment process. PMID- 26828332 TI - PCR-Based Analysis of Mitochondrial DNA Copy Number, Mitochondrial DNA Damage, and Nuclear DNA Damage. AB - Because of the role that DNA damage and depletion play in human disease, it is important to develop and improve tools to assess these endpoints. This unit describes PCR-based methods to measure nuclear and mitochondrial DNA damage and copy number. Long amplicon quantitative polymerase chain reaction (LA-QPCR) is used to detect DNA damage by measuring the number of polymerase-inhibiting lesions present based on the amount of PCR amplification; real-time PCR (RT-PCR) is used to calculate genome content. In this unit, we provide step-by-step instructions to perform these assays in Homo sapiens, Mus musculus, Rattus norvegicus, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Oryzias latipes, Fundulus grandis, and Fundulus heteroclitus, and discuss the advantages and disadvantages of these assays. PMID- 26828333 TI - Comparison of early and late decompressive craniectomy on the long-term outcome in patients with moderate and severe traumatic brain injury: a meta-analysis. AB - BACKGROUND: Several studies have searched whether early decompressive craniectomy (DC) can improve the long-term outcome of patients with moderate and severe traumatic brain injury (TBI). However, the effects of early DC remain unclear. The purpose of this meta-analysis was to assess whether early DC (time to surgery after injury <24 h) is better than late DC (>24 h) after moderate and severe TBI. METHOD: Two reviewers independently searched Pubmed, Embase, ISI web of science, the Cochrane Library and Scopus databases from inception to 4 November 2014. Studies comparing the long-term outcome of patients following early and late DC after TBI were included. The long-term outcomes were evaluated by Glasgow Outcome Score, Extended Glasgow Outcome Score. Newcastle-Ottawa Scale was used to assess the methodological quality of included studies. Characteristics of the selected studies were extracted. Pooled results were presented by odds ratios (ORs) with 95% CIs. I(2) was used to test heterogeneity. Pearson correlation coefficient was used to detect the relationship between bilateral pupil abnormality and unfavourable outcome. RESULTS: Five articles were eligible for this meta analysis. The pooled results of comparison of unfavourable outcome and mortality revealed no significant difference in the early and late groups (ORs: 1.469; 95% CIs: 0.495-4.362; p > 0.05; I(2 )=70.5% and ORs: 1.262; 95% CIs: 0.385-4.137; p > 0.05; I(2 )=77.6%, respectively). Pearson correlation coefficient indicated that bilateral pupil abnormality was positive related to the unfavourable outcomes and mortality (r = 0.833; p < 0.05) (0.829; p < 0.05). CONCLUSION: Bilateral pupil abnormality is positive related to unfavourable outcome and mortality in the patients following DC after moderate and severe TBI. Early DC may be more helpful to improve the long-term outcome of patients with refractory raised intracranial cerebral pressure after moderate and severe TBI. However, more RCTs with better control of patients with bilateral pupil abnormality divided into the early and late groups are needed in the future. PMID- 26828334 TI - Meeting the needs of cancer patients: is there a need for an organizational change? AB - As stated in the literature the most important needs of cancer patients are not adequately meet. Improving information, communication and education provided have not led to incisive changes in the organizational model of the oncology departments. The study contributes to this direction, by planning an "Integrated Operating Point" (I.O.P.) dedicated to cancer patients and their relatives in Italy. 42 Some professionals, patients and relatives were involved and 42 of them participated in focus group/or interviews. Results of thematic content analysis allow us to sketch out some key elements that I.O.P. should have in order to support cancer patients and their families. Integration of services, continuity of care, and cooperation between professionals involved are key elements that might qualify such organizational development. PMID- 26828335 TI - Multi-dimensional nursing form: a novel means of approaching nurse-led secondary cardiology prevention. AB - BACKGROUND AND AIM: Secondary prevention after an acute coronary syndrome (ACS) has proved to be effective in patients with coronary heart disease, and is strongly recommended by the international guidelines. However, there is a lack of widespread secondary preventive programmes in real-world clinical practice, even though it has been shown that these can be successfully conducted by nurses. METHOD AND RESULTS: We have designed a multicentre randomised trial involving patients with ACS in which nurses will fully coordinate secondary prevention in the intervention arm using a multidimensional nursing form after attending ad hoc teaching sessions. PMID- 26828336 TI - A cross selectional survey in a critical care: the job satisfaction and functioning team of the health professionals. AB - BACKGROUND AND AIM OF THE WORK: Health care workers, especially those who are part of the OS core, are essential in the delivery of services, as they represent the institution at the time of the contact with the user and they represent also the image of the organization. Health administrations, therefore, are called to improve the performance through a better motivation and satisfaction of the staff, in view of two strategic aspects: job satisfaction of professionals and team collaboration. METHOD: Between January and September 2014, a survey at the OU (UUOO) intensive care and sub intensive has been made inside three hospitals in Emilia Romagna. It' s been a multicentre cross-sectional quantitative study by administering a self-report questionnaire designed to investigate the different constructs. On 742 questionnaires were spread 454 professionals gave it back (response rate = 73%). Of those, 273 (60.1%) were nurses, 119 (26.2%) were physicians and 62 (13.7%) were healthcare operators. 62 (13.7%) Job Satisfaction was measured with the McCloskey Mueller Satisfaction Scale. Team Functioning was measured with the Index of Interprofessional Team Collaboration. RESULTS: Results from MANOVA indicated that physicians were less satisfied of scheduling than both nurses and healthcare operators. For professional opportunities, instead, healthcare operators showed the lower level of satisfaction. The participants seem to perceive a high level of team effectiveness and therefore the professionals involved in the care of critically ill patients than the two dimensions analysed, (reflection between the processes and interdependent roles), also state a greater tendency to respect the roles interdisciplinary, maintaining their professional autonomy and a lower tendency to use critical thinking to act professionally in order to improve the effectiveness of care provided. CONCLUSION: The study results oriented healthcare administrators, to take paths that feed the job satisfaction and the collaboration of professionals by developing the aspects investigated. Considering the shared perception among the professions studied, compared to the constructs under investigation, it seems to be clear how the routes should be designed in a systematic order to involve, in an integrated way the best professionals (nurses, doctors and OSS) involved in taking managing critical patients. No statistically significant difference have been found between these three professions considered, on most dimensions of job satisfaction investigated (relations between colleagues, 'social interactions, work-family balance, time work organization and working professional opportunity). There is a difference between two specific factors: the work time planning organization and wich is seen less by the nurses, while the job opportunities that are perceived less from the OOS. PMID- 26828337 TI - Analysis of obstetric care variables associated with caesarean section in low risk pregnancy patients. AB - BACKGROUND AND AIM OF THE WORK: The excessive use of caesarean section (CS) is an issue that is at the core of the political and healthcare management debate. This concern is particularly relevant for low-risk pregnancies, which does not theoretically require CS. Indeed, in Robson's classification, group 1 and 3 are considered at low-risk and in these groups, CS rate should be near to zero. The aim of the present work was to evaluate whether the non-compliance with guidelines by WHO is correlated to the increase in the rate of CS in Robson's class 1 and 3 in low-risk pregnancies. METHODS: A retrospective patient record study carried out in two hospitals of the northern Italy was used. RESULTS: Admission in active phase of labour and one-to-one care significantly decreased the likelihood of CS. On the contrary, an unjustified amniorrhexis and oxytocin administration increased the rate of CS. Other considered variables, instead, had not significant effect on CS rate. ROC curve on the computed risk index indicated a discrete sensibility and specificity, and that the better cut-off was up to 1. CONCLUSIONS: This research confirms the importance of one-to-one midwifery in management of low-risk pregnancy and labour. Moreover, it stress the risk that an excessive medicalization of low-risk pregnancy can drive to "unnatural" CS. PMID- 26828338 TI - Nursing students' experiences of and satisfaction with the clinical learning environment: the role of educational models in the simulation laboratory and in clinical practice. AB - BACKGROUND AND AIM OF THE WORK: Student satisfaction is an important element of the effectiveness of clinical placement, but there is little consensus in the literature as to the preferred model of clinical experience for undergraduate nursing students. The aim of this study was assess, for each academic year, students' perception of the roles of nurse teachers (NT) and clinical nurse supervisors (CNS) who perform tutoring in both apprenticeship and laboratories and to identify and evaluate students' satisfaction with the environment of clinical learning. METHOD: This analytic cross-sectional study was conducted in a sample of 173 nursing students in the Northern Italy. The research instrument used is the Clinical learning environment, supervision and nurse teacher (CLES+T) evaluation scale. Data were statistically analysed. RESULTS: 94% of our sample answered questionnaires. Students expressed a higher level of satisfaction with their training experiences. The highest mean value was in the sub-dimension "Pedagogical atmosphere on the ward". Third year students expressed higher satisfaction levels in their relationship with the CNS and lower satisfaction levels in their relationship with the NT. This result may be due to the educational model that is adopted in the course, in which the simulation laboratory didactic activities of the third year are conducted by CNS, who also supervises experiences of clinical learning in the clinical practice. CONCLUSIONS: The main finding in this study was that the students' satisfaction with the supervisory relationship and the role of NT depend on how supervision in the clinical practice and in the simulation laboratory is organized. PMID- 26828339 TI - Peer Tutoring and Clinical Stage: analysis of experience and potential applications in the First Level Degree Course in Nursing, section of Desenzano Del Garda. AB - Among the various methods of learning and experience in the literature, the methodology of Peer Tutoring is particularly important for the formation of the student nurses. The Peer Tutoring identifies a model of cooperative learning, aiming to activate a spontaneous process to transfer knowledge, emotions and experiences from some members of a group to other members of equal status but with a difference in the knowledge and cognitive skills or relational. The First level degree course in Nursing, section of Desenzano del Garda (Brescia, Italy) has been applying a methodology that can be defined as Peer Tutoring for the last four years. The applicability of the method is based on the coupling of an expert student of the 3rd year of the course to a group of students from the 1st or 2nd year. The study has the main objective to analyze the experience in the branch of Desenzano del Garda and see if the learning method of the Peer Tutoring is valid within the context of clinical internship. The study, of descriptive observational type, was conducted in the academic year 2013-2014. The samples in the research are two: the first sample consisted of 53 students in their first year of studies, 46 students of the 2nd year of the course and 30 students of the 3rd year of the course who attended the experience as tutoring students (students tutors), for a total of 129 students; the second sample consisted of 15 students of the 3rd year of the course who attended the experience of the Peer Tutoring applied to the Stage clinical students as tutors (students Tutor). The research allowed important information to be gathered regarding the utility and interventions to improve the quality of the project of Peer tutoring. Peer Tutoring is a learning methodology that works and that can be applied in learning pathways for nursing students. The training of students Tutor is a matter of considerable importance: in fact the students ask to be trained to respect the structure and functions of the organizations in which they are inserted, in the management of the groups, the educational skills and techniques and teaching strategies. PMID- 26828340 TI - Being an overseas student at the Faculty of Medicine and Surgery of the University of Parma: the perceptions of students from Cameroon. AB - There is a steady rise in the number of overseas students taking degree courses at the Medicine and Surgery faculties of Italian Universities. Numerous scholars, mainly from the English speaking world, have testified to the fact that a university teaching organisation aimed at attaining good levels of integration among students of differing cultural appurtenance is a prerequisite for success in the acquisition of good treatment practices. AIM: To explore the experience of students from Cameroon studying on the degree courses in Medicine and Surgery and in Nursing at the University of Parma, in order to discover the strong and weak points of the organisation of the courses so as to achieve a good process of integration. MATERIALS AND METHODS: An ethnographic study plan was adopted. In depth interviews were conducted with 20 students from Cameroon enrolled in the Faculty of Medicine of Parma University: 10 in the Degree Course in Medicine and Surgery and 10 in the Degree Course in Nursing. The interviews were recorded and analysed independently by two researchers, who then pooled their results. The age of the interviewed ranges from 24 to 31, the average age is 26,5. RESULTS: Independently from the attended degree course, most of the students interviewed claim that the process of integration has not been very successful: despite attempts to open up a dialogue with their Italian counterparts in order to get to know them, the latter showed no signs of willingness to integrate. Some students develop a self-critical attitude, maintaining that it would be a good idea to strengthen their awareness of their own cultural identity so as to start from a firm base in the attempt to open up to the host society without defensive attitudes that lead to ostracism. The difficulties of socialisation are compounded by those of learning, which many attribute to the language difficulties and some to the differing academic organisation between country of origin and host country. DISCUSSION: The problem of the difficulties of integration of overseas students is not new. In other geographical locations, changes to syllabuses designed to solve the problem, at least in part, have been proposed and successfully implemented. The Italian situation is a particular one, and this preliminary study yields some ideas for the implementation of changes to the syllabuses of the Italian universities. PMID- 26828341 TI - The dynamics of social capital and health. AB - In the wake of Robert Putnam's arrival in Italy to study regionalization, this review of the literature on social capital aimed to establish whether current knowledge, social or socio-anthropological research have yielded new findings on how social capital is built and maintained or developed in a community and to what extent this influences social well-being. This is particularly important for those working in the health sector to make sure that health-related decision making and behaviour foster rather than destroy the development of social capital. Our literature search was based on specific articles published in scientific journals in the humanist, managerial and medical fields, book titles or subtitles containing references to "social capital or social cooperation or reciprocity". Our findings led us to the conclusion that a complex series of coordinated actions are required for social capital to develop and that, once developed, social capital has a positive impact on social relations, economic results and social stability. In addition, we understood why it is useful to retain three stages, conditioning, development and capitalization, in modelling the development of social capital. Conditioning requires transparency, pragmatism and long-term vision. Development and capitalization require the predominant variables to be chosen. The development of social capital is part of a good strategy for health promotion and prevention. PMID- 26828342 TI - The Effect of Different Forms of Centering in Hierarchical Linear Models. AB - Multilevel models are becoming increasingly used in applied educational social and economic research for the analysis of hierarchically nested data. In these random coefficient regression models the parameters are allowed to differ over the groups in which the observations are nested. For computational ease in deriving parameter estimates, predictors are often centered around the mean. In nested or grouped data, the option of centering around the grand mean is extended with an option to center within groups or contexts. Both are statistically sound ways to improve parameter estimation. In this article we study the effects of these two different ways of centering, in comparison to the use of raw scores, on the parameter estimates in random coefficient models. The conclusion is that centering around the group mean amounts to fitting a different model from that obtained by centering around the grand mean or by using raw scores. The choice between the two options for centering can only be made on a theoretical basis. Based on this study, we conclude that centering rules valid for simple models, such as the fixed coefficients regression model. are no longer applicable to more complicated models, such as the random coefficient model. We think researchers should be made aware of the consequences of the choice of particular centering options. PMID- 26828343 TI - Goodness of Fit in Item Response Models. AB - It is shown that goodness-of-fit criteria developed for the evaluation of multivariate structural models can be applied to assist in evaluating the dimensionality of a test consisting of binary items, and correlative methods regularly employed in factor analysis can be used to diagnose causes of misfit. PMID- 26828344 TI - Testing for Equivalence of Measurement Scales: Simple Structure and Metric Invariance Reconsidered. AB - Most quantitative comparisons of interest are based on scores obtained from multi item scales. In order for such comparisons to be valid and meaningful, conventional thinking dictates that simple structure and metric invariance must be satisfied at the level of individual items. However, it is proposed here that the use of multi-item scales requires only that conditions of simple structure and metric invariance be satisfied at the scale level, that is, for hypothesized sets of items as a whole rather than each item individually. The proposed concepts can be implemented within the context of confirmatory factor analysis (CFA) by imposing constraints on mean factor loadings and intercepts of item sets rather than loadings and intercepts of each individual item. Further, the present method is proposed as a conceptual alternative to the specification of measurement models that is currently predominant in CFA. PMID- 26828345 TI - Relationships Among Measurement Models for Dichotomous Variables and Associated Composites. PMID- 26828346 TI - Some Comments on Labouvie and Ruetsch. PMID- 26828347 TI - Testing for Equivalence of Measurement Scales: A Comment. PMID- 26828348 TI - Two Wrongs May Not Make a Right. PMID- 26828349 TI - "...and expectation fainted, longing for what it had not." Comments on Labouvie and Ruetsch's "Testing for Equivalence...". PMID- 26828350 TI - On Methods for Comparing Apples and Oranges. PMID- 26828351 TI - Apples Aren't Oranges And Squares Aren't Rectangles, But... PMID- 26828352 TI - Not Only But Also. PMID- 26828353 TI - Two Wrongs Still Do Not Make a Right. PMID- 26828354 TI - Further Commentary on Labouvie & Ruetsch's "Testing for Equivalence of Measurement Scales...". PMID- 26828355 TI - Wholes or Parts? PMID- 26828356 TI - Progression of cartilage degeneration and clinical symptoms in obese and overweight individuals is dependent on the amount of weight loss: 48-month data from the Osteoarthritis Initiative. AB - OBJECTIVE: To investigate compositional cartilage changes measured with 3T MRI based T2 values over 48 months in overweight and obese individuals with different degrees of weight loss (WL) and to study whether WL slows knee cartilage degeneration and symptom worsening. DESIGN: We studied participants from the Osteoarthritis Initiative with risk factors or radiographic evidence of mild to moderate knee osteoarthritis with a baseline BMI >=25 kg/m(2). We selected subjects who over 48 months lost a, moderate (BMI change, 5-10%WL, n = 180) or large amount of weight (>=10%WL, n = 78) and frequency-matched these to individuals with stable weight (<3%, n = 258). Right knee cartilage T2 maps of all compartments and grey-level co-occurrence matrix (GLCM) texture analyses were evaluated and associations with WL and clinical symptoms (WOMAC subscales for pain, stiffness and disability) were assessed using multivariable regression models. RESULTS: The amount of weight change was significantly associated with change in cartilage T2 of the medial tibia (beta 0.9 ms, 95% CI 0.4 to 1.1, P = 0.001). Increase of T2 in the medial tibia was significantly associated with increase in WOMAC pain (beta 0.5 ms, 95% CI 0.2 to 0.6, P = 0.02) and disability (beta 0.03 ms, 95% CI 0.003 to 0.05, P = 0.03). GLCM contrast and variance over all compartments showed significantly less progression in the >10%WL group compared to the stable weight group (both comparisons, P = 0.04). CONCLUSIONS: WL over 48 months is associated with slowed knee cartilage degeneration and improved knee symptoms. PMID- 26828357 TI - The contribution of collagen fibers to the mechanical compressive properties of the temporomandibular joint disc. AB - OBJECTIVE: The Temporomandibular Joint (TMJ) disc is a fibrocartilaginous structure located between the mandibular condyle and the temporal bone, facilitating smooth movements of the jaw. The load-bearing properties of its anisotropic collagenous network have been well characterized under tensile loading conditions. However, recently it has also been speculated that the collagen fibers may contribute dominantly in reinforcing the disc under compression. Therefore, in this study, the structural-functional role of collagen fibers in mechanical compressive properties of TMJ disc was investigated. DESIGN: Intact porcine TMJ discs were enzymatically digested with collagenase to disrupt the collagenous network of the cartilage. The digested and non-digested articular discs were analyzed mechanically, biochemically and histologically in five various regions. These tests included: (1) cyclic compression tests, (2) biochemical quantification of collagen and glycosaminoglycan (GAG) content and (3) visualization of collagen fibers' alignment by polarized light microscopy (PLM). RESULTS: The instantaneous compressive moduli of the articular discs were reduced by as much as 50-90% depending on the region after the collagenase treatment. The energy dissipation properties of the digested discs showed a similar tendency. Biochemical analysis of the digested samples demonstrated an average of 14% and 35% loss in collagen and GAG, respectively. Despite the low reduction of collagen content the PLM images showed considerable perturbation of the collagenous network of the TMJ disc. CONCLUSIONS: The results indicated that even mild disruption of collagen fibers can lead to substantial mechanical softening of TMJ disc undermining its reinforcement and mechanical stability under compression. PMID- 26828358 TI - Value of tomosynthesis for lesion evaluation of small joints in osteoarthritic hands using the OARSI score. AB - OBJECTIVE: To determine the diagnostic performance of tomosynthesis in depicting osteoarthritic lesions in comparison to conventional radiographs, with use of computed tomography (CT) as standard-of-reference. METHODS: Imaging of 12 cadaveric hands was performed with tomosynthesis in dorso-palmar (dp) projection, conventional radiographs (dp) and multi-detector CT. Distal interphalangeal joint (DIP)II, DIPIII, proximal interphalangeal joint (PIP)II, PIPIII, first carpometacarpal (CMC) and scaphotrapezotrapezoidal joint (STT) were graded by two independent readers using the Osteoarthritis Research Society International (OARSI) score. The mean score for each feature was calculated for all modalities. Additional wrists were evaluated for presence of calcium pyrophosphate disease (CPPD). CT served as reference-standard. Inter-reader agreement (ICC) was calculated. RESULTS: Comparing tomosynthesis and conventional radiographs to CT, the sensitivity for the presence of osteophytes was 95,7% vs 65,2%; for joint space narrowing 95,8% vs 52,1%; for subchondral sclerosis 61,5% vs 51,3%; for lateral deformity 83.3% vs 83,3%; and for subchondral cysts 45,8% vs 29,2%. Erosions were not present. While tomosynthesis showed no significant difference in OARSI score grading to CT (mean OARSI-score CT: 16.8, SD = 10.6; mean OARSI score Tomosynthesis: 16.3, SD = 9.6; P = 0.84), conventional radiographs had significant lower mean OARSI scores (mean OARSI-score X-ray: 11.1, SD = 8.3; P = 0.04). Inter-reader agreement for OARSI scoring was excellent (ICC = 0.99). CPPD calcifications present in CT, were also visible with tomosynthesis, but not with conventional radiography. CONCLUSION: In conclusion, tomosynthesis depicts more osteoarthritic changes in the small joints of the hand than conventional radiography using the OARSI scoring system and CT as the standard of reference. PMID- 26828359 TI - The Roles of MicroRNA-141 in Human Cancers: From Diagnosis to Treatment. AB - Cancer remains one of the most threatening causes of human health impairment, and the mechanisms underlying tumorigenesis have not been completely characterized. MicroRNAs (miRNAs) are a group of endogenous, small (18~25 nucleotides) non coding RNAs which negatively regulate gene expressions by directly binding to the 3'-untranslated regions (3'-UTRs) of the target messenger RNAs (mRNAs). Increasing evidence has demonstrated abnormal miRNA profiles and confirmed their involvement in tumor initiation and progression. As one important member of the miR-200 family, microRNA (miR)-141 is aberrantly expressed in many human malignant tumors, participating in various cellular processes including epithelial-mesenchymal transition (EMT), proliferation, migration, invasion, and drug resistance. In the present review, we briefly describe the mechanisms underlying miR-141-mediated tumorigenesis and the possible future of miR-141 as a potential diagnostic and prognostic parameter as well as therapeutic target in clinical applications. PMID- 26828361 TI - Correction: Modulation of the Surface Proteome through Multiple Ubiquitylation Pathways in African Trypanosomes. PMID- 26828360 TI - An Evaluation of the Cobas4800 HPV Test on Cervico-Vaginal Specimens in Liquid versus Solid Transport Media. AB - OBJECTIVES: Determine the ability of the Cobas 4800 assay to detect high-risk human papillomavirus (HrHPV) and high-grade cervical lesions when using cervico vaginal samples applied to liquid medium and solid media cards compared to a direct cervical sample. METHODS: Two cervico-vaginal specimens (pseudo self collected) were obtained from 319 women. One was applied to an iFTA Card (FTA) then the brush placed in liquid-based medium (LSELF); the other was applied to a new solid media: POI card (POI). The clinical performance of Cobas4800 assay using the three aforementioned specimens was compared to direct collected endocervical specimens in liquid media (LDOC). RESULTS: The overall agreements of HrHPV detection were 84.2% (LSELF vs. LDOC), 81.0% (FTA vs. LDOC), and 82.3% (POI vs. LDOC). LSELF, FTA and POI identified 98.0%, 79.6%, and 97.5% positive cases of LDOC. Sensitivity to identify CIN2+ were 98.4% (LSELF), 73.8% (FTA), 95.1% (POI), and 93.4% (LDOC) respectively. FTA had 78.1% and 90.4% agreement with the LSELF samples for all HrHPV and HPV16/18 detection respectively, while POI had 91.6% for both. CONCLUSIONS: Cobas4800 HPV test combined with cervico-vaginal specimens applied to both liquid media and POI solid card are accurate to detect HrHPV infection and high-grade cervical lesions as compared with direct endocervical samples in liquid media. PMID- 26828362 TI - Modeling the Role of Networks and Individual Differences in Inter-Group Violence. AB - There is significant heterogeneity within and between populations in their propensity to engage in conflict. Most research has neglected the role of within group effects in social networks in contributing to between-group violence and focused instead on the precursors and consequences of violence, or on the role of between-group ties. Here, we explore the role of individual variation and of network structure within a population in promoting and inhibiting group violence towards other populations. Motivated by ethnographic observations of collective behavior in a small-scale society, we describe a model with differentiated roles for individuals embedded within friendship networks. Using a simple model based on voting-like dynamics, we explore several strategies for influencing group level behavior. When we consider changing population level attitude changes and introducing control nodes separately, we find that a particularly effective control strategy relies on exploiting network degree. We also suggest refinements to our model such as tracking fine-grained information spread dynamics that can lead to further enrichment in using evolutionary game theory models for sociological phenomena. PMID- 26828363 TI - Food Web Assembly Rules for Generalized Lotka-Volterra Equations. AB - In food webs, many interacting species coexist despite the restrictions imposed by the competitive exclusion principle and apparent competition. For the generalized Lotka-Volterra equations, sustainable coexistence necessitates nonzero determinant of the interaction matrix. Here we show that this requirement is equivalent to demanding that each species be part of a non-overlapping pairing, which substantially constrains the food web structure. We demonstrate that a stable food web can always be obtained if a non-overlapping pairing exists. If it does not, the matrix rank can be used to quantify the lack of niches, corresponding to unpaired species. For the species richness at each trophic level, we derive the food web assembly rules, which specify sustainable combinations. In neighboring levels, these rules allow the higher level to avert competitive exclusion at the lower, thereby incorporating apparent competition. In agreement with data, the assembly rules predict high species numbers at intermediate levels and thinning at the top and bottom. Using comprehensive food web data, we demonstrate how omnivores or parasites with hosts at multiple trophic levels can loosen the constraints and help obtain coexistence in food webs. Hence, omnivory may be the glue that keeps communities intact even under extinction or ecological release of species. PMID- 26828364 TI - Correction: The Schistosoma mansoni Cytochrome P450 (CYP3050A1) Is Essential for Worm Survival and Egg Development. PMID- 26828365 TI - First-Person Perspective Virtual Body Posture Influences Stress: A Virtual Reality Body Ownership Study. AB - In immersive virtual reality (IVR) it is possible to replace a person's real body by a life-sized virtual body that is seen from first person perspective to visually substitute their own. Multisensory feedback from the virtual to the real body (such as the correspondence of touch and also movement) can also be present. Under these conditions participants typically experience a subjective body ownership illusion (BOI) over the virtual body, even though they know that it is not their real one. In most studies and applications the posture of the real and virtual bodies are as similar as possible. Here we were interested in whether the BOI is diminished when there are gross discrepancies between the real and virtual body postures. We also explored whether a comfortable or uncomfortable virtual body posture would induce feelings and physiological responses commensurate with the posture. We carried out an experiment with 31 participants in IVR realized with a wide field-of-view head-mounted display. All participants were comfortably seated. Sixteen of them were embodied in a virtual body designed to be in a comfortable posture, and the remainder in an uncomfortable posture. The results suggest that the uncomfortable body posture led to lesser subjective BOI than the comfortable one, but that participants in the uncomfortable posture experienced greater awareness of their autonomic physiological responses. Moreover their heart rate, heart rate variability, and the number of mistakes in a cognitive task were associated with the strength of their BOI in the uncomfortable posture: greater heart rate, lower heart rate variability and more mistakes were associated with higher levels of the BOI. These findings point in a consistent direction--that the BOI over a body that is in an uncomfortable posture can lead to subjective, physiological and cognitive effects consistent with discomfort that do not occur with the BOI over a body in a comfortable posture. PMID- 26828366 TI - Population Size Estimation of Men Who Have Sex with Men in Tbilisi, Georgia; Multiple Methods and Triangulation of Findings. AB - INTRODUCTION: An accurate estimation of the population size of men who have sex with men (MSM) is critical to the success of HIV program planning and to monitoring of the response to epidemic as a whole, but is quite often missing. In this study, our aim was to estimate the population size of MSM in Tbilisi, Georgia and compare it with other estimates in the region. METHODS: In the absence of a gold standard for estimating the population size of MSM, this study reports a range of methods, including network scale-up, mobile/web apps multiplier, service and unique object multiplier, network-based capture recapture, Handcock RDS-based and Wisdom of Crowds methods. To apply all these methods, two surveys were conducted: first, a household survey among 1,015 adults from the general population, and second, a respondent driven sample of 210 MSM. We also conducted a literature review of MSM size estimation in Eastern European and Central Asian countries. RESULTS: The median population size of MSM generated from all previously mentioned methods was estimated to be 5,100 (95% Confidence Interval (CI): 3,243~9,088). This corresponds to 1.42% (95%CI: 0.9%~2.53%) of the adult male population in Tbilisi. CONCLUSION: Our size estimates of the MSM population (1.42% (95%CI: 0.9%~2.53%) of the adult male population in Tbilisi) fall within ranges reported in other Eastern European and Central Asian countries. These estimates can provide valuable information for country level HIV prevention program planning and evaluation. Furthermore, we believe, that our results will narrow the gap in data availability on the estimates of the population size of MSM in the region. PMID- 26828367 TI - Dietary Probiotics Affect Gastrointestinal Microbiota, Histological Structure and Shell Mineralization in Turtles. AB - Probiotics are widely used in nutrition, and their mode of action is intensively studied in mammals and birds; however, it is almost unknown in reptiles. In the present study, Trachemys scripta scripta and Sternotherus odoratus were used to assess the effects of dietary probiotics on chelonian gastrointestinal tract microecology. In the first, 20-week experiment, 40 young T. s. scripta were randomly distributed to four experimental groups: 1st, (CON)--with no additives; 2nd, (SSPA) with Bacillus subtilis PB6; 3rd, (MSP)--with multiple strain probiotic; and 4th, (SSPB) with Bacillus subtilis C-3102. The first study has shown that SSPA and MSP decreased the numbers of total bacteria, Enterobacteriace, Staphylococcus sp. and Streptococcus sp. excreted to water and increased the villous height and mucosa thickness in duodenum. SSPB improved the duodenal microstructure; however, it also increased numbers of kanamycin and vancomycin resistant bacteria, Staphylococcus sp. and Streptococcus sp., in water. In the second, 52-week experiment, 30 S. odoratus were randomly assigned to three dietary treatments. CON, SSPA and MSP groups. The MSP preparation increased the body weight gain, crude ash, Ca and P share in the turtles' shells. Both probiotics affected duodenal histomorphology. SSPA decreased the villous height, while MSP increased the villous height and mucosa thickness, and decreased the crypt depth. SSPA decreased the concentrations of bacteria excreted to water. In the case of intestinal microbiota, bacteria suppressing effects were observed in the case of both probiotics. MSP increased the number of Bifidobacterium sp. and Lactobacillus sp./Enteroccoccus sp., and decreased the number of Clostridium perfringens and Campylobacter sp. in the small intestine. In the large intestine it lowered, amongst others, Bacteroides-Pervotella cluster, Clostridium leptum subgroup and Clostridium perfringens numbers. The above-mentioned results suggest that probiotics are useful in turtle nutrition due to their positive effects on growth performance, shell mineralization, duodenal histomorphology and microbiota. PMID- 26828368 TI - Computed modeling of humeral mid-shaft fracture treated by bundle nailing. AB - Elastic bundle nailing is a method for simple humeral mid-shaft fracture osteosynthesis. The aim of our subsequent numerical simulations was to find out torsional and bending stiffness of an elastic bundle nailed humerus. Parametrical 3D numerical model was developed. The diameter of nails was the varying parameter of 1.8, 2.5, 3 and 4 mm. From our results can be seen that the bending stiffness in bundle nailing technique does not depend on nail diameter. On the contrary the torsional stiffness does highly depend on nail diameter. The dependency of the maximal stress on a nail diameter during bending and torsion of the humerus is non-linear. It can be seen that the higher diameter is used the higher stress occurs. Achieved results allow us for the recommendation of optimal nail diameter for this method, which lies between 2 and 3 mm. PMID- 26828369 TI - Synthesis of 5-(S)-HETE, 5-(S)-HEPE and (+)-zooxanthellactone: Three hydroxylated polyunsaturated fatty acid metabolites. AB - Short and stereoselective syntheses of the two hydroxylated polyunsaturated fatty acid metabolites, namely 5-(S)-HETE and 5-(S)-HEPE, are reported in 23% and 30% overall yields, respectively. In addition, synthesis of the polyunsaturated fatty acid natural product (+)-zooxanthellactone has been achieved in 19% overall yield. The three aforementioned compounds have been conveniently prepared in six steps, starting from the corresponding commercially available polyunsaturated fatty acids arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid, respectively. All three hydroxylated polyunsaturated natural products were prepared using a biomimetic synthesis. PMID- 26828370 TI - Cognitive functioning and deep transcranial magnetic stimulation (DTMS) in major psychiatric disorders: A systematic review. AB - Deep transcranial magnetic stimulation (DTMS) is a non-invasive brain stimulation method mostly utilised in the treatment of major depression. The aim of the current study was to systematically review the literature on the cognitive effects of DTMS applied with the H-coil system in major psychiatric disorders. Following a literature search in PsycInfo and PubMed (any time to December 2015), 13 out of 32 studies on DTMS and cognitive functioning were included in the current review. Three studies included 38 healthy participants, eight studies included 158 unipolar or bipolar depression patients and two studies included 45 schizophrenia patients. Low-frequency DTMS (1-3 sessions) had little effect on cognitive functioning in healthy participants. The most consistent cognitive and clinical improvements were reported in the short-term (after 20 daily sessions of high-frequency DTMS with H1-coil) in studies with major depression patients. There was also a trend towards a short-term cognitive and clinical improvement in studies with schizophrenia patients. High-frequency DTMS might improve cognitive functioning and alleviate clinical symptoms in the short-term, particularly in major depression. However, this conclusion is based on data from mostly uncontrolled, open-label studies with patients receiving concurrent antidepressants or antipsychotics. Randomised, sham-controlled trials are needed to investigate the magnitude of the cognitive outcomes of DTMS in the short-term and beyond the daily stimulation phase in major psychiatric disorders. PMID- 26828371 TI - Effects of context on risk taking and decision times in obsessive-compulsive disorder. AB - Despite the fact that OCD patients show altered decision making in everyday life, few studies have investigated how patients make risky decisions and what contextual factors impact choices. We investigated cognitive context with the use of the "framing effect" task, which investigates decision making based on whether monetarily equivalent choice options are framed in terms of a potential to either lose (lose $20 out of $50) or gain (gain $30 out of $50) money. In addition, we manipulated social context by providing positive or neutral feedback on subjects' choices. Overall, participants were risk taking for options framed in terms of potential loss and risk averse for options framed in terms of potential gain (the classic framing effect). Although OCD patients were generally more risk averse, the effect of the frame on choices did not differ significantly from healthy participants and choices were not impacted by social context. Within OCD patients, greater self-reported indecisiveness was associated with a larger effect of the frame on choices. OCD patients were also significantly slower to make choices in the loss compared to gain frame, an effect that was not observed among healthy participants. Overall, our results suggest that the framing of choice options has a differential effect on decision times but not the actual choices made by OCD patients, and that patients are not sensitive to social feedback when making choices. The correlation between indecisiveness and the framing effect in OCD suggests that further work interrogating the relationship between specific symptoms and decision making among patients may yield new insights into the disorder. PMID- 26828372 TI - Cognitive remediation in schizophrenia: A methodological appraisal of systematic reviews and meta-analyses. AB - OBJECTIVE: Systematic reviews and meta-analyses are a primary source of evidence when evaluating the benefit(s) of cognitive remediation (CR) in schizophrenia. These studies are designed to rigorously synthesize scientific literature; however, cannot be assumed to be of high methodological quality. The aims of this report were to: 1) review the use of systematic reviews and meta-analyses regarding CR in schizophrenia; 2) conduct a systematic methodological appraisal of published reports examining the benefits of this intervention on core outcome domains; and 3) compare the correspondence between methodological and reporting quality. METHOD: Electronic databases were searched for relevant articles. Twenty one reviews met inclusion criteria and were scored according to the AMSTAR checklist-a validated scale of methodological quality. Five meta-analyses were also scored according to PRISMA statement to compare 'quality of conduct' with 'quality of reporting'. RESULTS: Most systematic reviews and meta-analyses shared strengths and fell within a 'medium' level of methodological quality. Nevertheless, there were consistent areas of potential weakness that were not addressed by most reviews. These included the lack of protocol registration, uncertainty regarding independent data extraction and consensus procedures, and the minimal assessment of publication bias. Moreover, quality of conduct may not necessarily parallel quality of reporting, suggesting that consideration of these methods independently may be important. CONCLUSIONS: Reviews concerning CR for schizophrenia are a valuable source of evidence. However, the methodological quality of these reports may require additional consideration. Enhancing quality of conduct is essential for enabling research literature to be interpreted with confidence. PMID- 26828373 TI - U6 snRNA intron insertion occurred multiple times during fungi evolution. AB - U6 small nuclear RNAs are part of the splicing machinery. They exhibit several unique features setting them appart from other snRNAs. Reports of introns in structured non-coding RNAs have been very rare. U6 genes, however, were found to be interrupted by an intron in several Schizosaccharomyces species and in 2 Basidiomycota. We conducted a homology search across 147 currently available fungal genome and identified the U6 genes in all but 2 of them. A detailed comparison of their sequences and predicted secondary structures showed that intron insertion events in the U6 snRNA were much more common in the fungal lineage than previously thought. Their positional distribution across the entire mature snRNA strongly suggests a large number of independent events. All the intron sequences reported here show canonical splice site and branch site motifs indicating that they require the splicesomal pathway for their removal. PMID- 26828374 TI - Venomous extract protein profile of Brazilian tarantula Grammostola iheringi: searching for potential biotechnological applications. AB - Tarantula spiders, Theraphosidae family, are spread throughout most tropical regions of the world. Despite their size and reputation, there are few reports of accidents. However, like other spiders, their venom is considered a remarkable source of toxins, which have been selected through millions of years of evolution. The present work provides a proteomic overview of the fascinating complexity of the venomous extract of the Grammostola iheringi tarantula, obtained by electrical stimulation of the chelicerae. For analysis a bottom-up proteomic approach Multidimensional Protein Identification Technology (MudPIT) was used. Based on bioinformatics analyses, PepExplorer, a similarity-driven search tool that identifies proteins based on phylogenetically close organisms, a total of 395 proteins were identified in this venomous extract. Most of the identifications (~70%) were classified as predicted (21%), hypothetical (6%) and putative (37%), while a small group (6%) had no predicted function. Identified molecules matched with neurotoxins that act on ions channels; proteases, such as serine proteases, metalloproteinases, cysteine proteinases, aspartic proteinases, carboxypeptidases and cysteine-rich secretory enzymes (CRISP) and some molecules with unknown target. Additionally, non-classical venom proteins were also identified. Up to now, this study represents, to date, the first broad characterization of the composition of G. iheringi venomous extract. Our data provides a tantalizing insight into the diversity of proteins in this venom and their biotechnological potential. SIGNIFICANCE: Animal venoms contain a diversity of molecules able to bind to specific cell targets. Due to their biochemical and physiological properties, these molecules are interesting for medical and biotechnological purposes. In this study, a large number of components of the venomous extract of the spider Grammostola iheringi were identified by the MudPIT technique. It was demonstrated that this approach is a sensitive and adequate method to achieve a broad spectrum of information about animal venoms. Using this bottom-up proteomic method, classical and non-classical venom proteins were identified which stimulate new interest in the systematic research of their protein components. PMID- 26828375 TI - FastaHerder2: Four Ways to Research Protein Function and Evolution with Clustering and Clustered Databases. AB - The accelerated growth of protein databases offers great possibilities for the study of protein function using sequence similarity and conservation. However, the huge number of sequences deposited in these databases requires new ways of analyzing and organizing the data. It is necessary to group the many very similar sequences, creating clusters with automated derived annotations useful to understand their function, evolution, and level of experimental evidence. We developed an algorithm called FastaHerder2, which can cluster any protein database, putting together very similar protein sequences based on near-full length similarity and/or high threshold of sequence identity. We compressed 50 reference proteomes, along with the SwissProt database, which we could compress by 74.7%. The clustering algorithm was benchmarked using OrthoBench and compared with FASTA HERDER, a previous version of the algorithm, showing that FastaHerder2 can cluster a set of proteins yielding a high compression, with a lower error rate than its predecessor. We illustrate the use of FastaHerder2 to detect biologically relevant functional features in protein families. With our approach we seek to promote a modern view and usage of the protein sequence databases more appropriate to the postgenomic era. PMID- 26828376 TI - Gender dysphoria in adolescence. AB - Adolescents presenting with gender-related concerns are increasingly seeking support from providers from a variety of disciplines within health care settings across the world. For those treating young people who meet the criteria for the DSM 5 diagnosis of gender dysphoria (GD), complex decisions in clinical care are common. Defining best practice with this population with respect to interventions that span mental health, physical, and surgical domains can be challenging, given a relative dearth of empirical data available; yet practice guidelines have emerged from different professional organizations which can aid with this. For this review paper, a broad literature search was performed to identify relevant studies pertaining to the care of adolescents with GD. In addition, an overview of trends in clinical practice, including shifts in conceptualization of how clinicians and patients define care that is considered affirming when working with this population, is described. This paper explores the characteristics of referral patterns to specialized clinics, provides a brief overview of gender identity development in adolescence, and then describes the phenomenology of known aetiological factors and co-occurring psychiatric issues in adolescents with GD. Additionally, clinical management considerations that detail assessment aims and common treatment interventions across disciplines will be explored. PMID- 26828377 TI - Specific features of pharmacokinetics in children. AB - Human growth and development consist of a continuum of biological events. The impact of these developmental changes in drug disposition is largely related to changes in the body composition (e.g. body water content, plasma protein concentrations) and in the function of organs important in metabolism (e.g. the liver) and excretion (e.g. the kidney). The gastric emptying time during the neonatal period is prolonged, as well as intestinal motility. The ratio of body surface area to body weight is higher in children than in adults, which results in higher absorption of locally applied corticosteroids. Lower plasma protein levels and a higher body water content compared to adults may lead to diminished drug distribution. Phase I drug metabolizing system develops quickly and reaches adult levels between the third and sixth year of age. In newborns up to 3 months, the sulphotransferase activity is more developed than glucuronidation. Glomerular filtration, normalized to body surface area, approaches adult levels by 6 months of age. During the first decade of life, these changes are dynamic and can be non linear and discordant, making standardized dosing inadequate. During rapid phases of growth/development, drug disposition and response may be altered. The main goal is to optimize drug therapy in children. This can be achieved through a fundamental understanding of how ontogeny influences pharmacokinetics. PMID- 26828378 TI - Insights into the regulation of C4 leaf development from comparative transcriptomic analysis. AB - C4 photosynthesis is more efficient than C3 photosynthesis for two reasons. First, C4 plants have evolved a repertoire of C4 enzymes to enhance CO2 fixation. Second, C4 leaves have Kranz anatomy with a high vein density in which the veins are surrounded by one layer of bundle sheath (BS) cells and one layer of mesophyll (M) cells. The BS and M cells are not only functionally well differentiated, but also well-coordinated for rapid transport of photo assimilates between the two types of photosynthetic cells. Recent comparative transcriptomic and anatomical analyses of C3 and C4 leaves have revealed early onset of C4-related processes in leaf development, suggesting that delayed mesophyll differentiation contributes to higher C4 vein density, and have identified some candidate regulators for the higher vein density in C4 leaves. Moreover, comparative transcriptomics of maize husk (C3) and foliar leaves (C4) has identified a cohort of candidate regulators of Kranz anatomy development. In addition, there has been major progress in the identification of transcription factor binding sites, greatly increasing our knowledge of gene regulation in plants. PMID- 26828379 TI - Functional cereals for production in new and variable climates. AB - Adaptation of cereal crops to variable or changing climates requires that essential quality attributes are maintained to deliver food that will be acceptable to human consumers. Advances in cereal genomics are delivering insights into the molecular basis of nutritional and functional quality traits in cereals and defining new genetic resources. Understanding the influence of the environment on expression of these traits will support the retention of these essential functional properties during climate adaptation. New cereals for use as whole grain or ground to flour for other food products may be based upon the traditional species such as rice and wheat currently used in these food applications but may also include new options exploiting genomics tools to allow accelerated domestication of new species. PMID- 26828380 TI - Phosphorylated AMP-activated protein kinase slows down the atrial fibrillation progression by activating Connexin43. PMID- 26828381 TI - Transverse sternotomy for atrioventricular and biventricular pacing lead implantations. PMID- 26828382 TI - Data supporting the use of the radial approach as the default strategy in octogenarians undergoing primary-PCI? AB - BACKGROUND: There is a significant increase in the number of octogenarians undergoing Primary Percutaneous Intervention (PPCI) for ST elevation myocardial infarction Objective: To analyze one year all cause mortality in octogenarians who are admitted with a STEMI and received PPCI in a tertiary cardiac centre in the UK, and to observe the impact of the mode of vascular access on mortality. METHODS: We reviewed registry records of consecutive STEMI patients(N=2951), admitted between 2005 and 2011.Kaplan-Meier and Cox regression analyses were used to compare mortality between OG and Age group (50-79) years. RESULTS: Of the total population, 8.1% (n=241, Mean age: 85.3 yrs. (SD: 3.4)) were OG of whom 53.5% were male. Use of femoral arterial access (63%) was significantly higher among OG (P=0.04) compared to radial route. In univariate analysis, event free survival was significantly lower in OG (log rank test, P=0.001) compared to other age group. All cause mortality was significantly higher among patients who had femoral arterial access compared to radial route (log rank test, P=0.03) in OG. In Cox regression analysis conventional risk factors femoral access remained significantly associated with one year all cause mortality (Beta:-1.9(SE: 0.9, P=0.04). CONCLUSION: In our analysis, OG who received PPCI for STEMI have disproportionately higher one year all cause mortality compared to younger age group. Use of femoral arterial access appears to be independently associated with this excess mortality. Radial access preferred to be the safer and prime option in this high risk population and warrants further investigations. PMID- 26828383 TI - Endoplasmic reticulum stress-induced apoptosis: A possible role in myocardial ischemia-reperfusion injury. PMID- 26828384 TI - Autosomal recessive atrial disease presenting with sick sinus syndrome (SSS), right atrial fibrosis and biatrial dilatation: Clinical impact of genetic diagnosis. PMID- 26828385 TI - Hypophosphatemia as a novel etiology of Brugada Phenocopy. PMID- 26828386 TI - Anticoagulant therapy after venous thromboembolism and 10-year mortality. AB - BACKGROUND: Pulmonary embolism (PE) is associated with a higher long-term mortality than deep vein thrombosis (DVT). This association may be related to inadequate antithrombotic therapy. METHODS: Incident VTE patients during the period 1997-2012 were identified in Danish nationwide registries. Two landmark populations were defined, consisting of patients alive at 30 days (30 d), and at 180 days (180 d) after discharge. Patients were classified according to anticoagulant usage at the landmark (30 d: prescription purchase 0-30 d post discharge; 180 d: prescription purchase in 0-30 d and 90-180 d). Mortality rates were compared using multivariate Cox regression. RESULTS: The 30 d mortality risk among PE patients was high compared to DVT patients (19.9% vs. 4.4%). In the 30 d landmark population (n=62695), 34.9% of DVT patients and 21.3% of PE patients had not redeemed a prescription for anticoagulants. There was no material difference in 10-year mortality between anticoagulated PE patients and anticoagulated DVT patients. There was a higher 10-year mortality rate among non-anticoagulated PE patients compared to anticoagulated DVT patients (MRR: 1.26, 95% CI: 1.20-1.33). Findings in the 180 d-landmark population also indicated materially similar 10 year mortality rates between anticoagulated PE patients and anticoagulated DVT patients. CONCLUSIONS: The 10-year mortality rate of patients surviving the initial 30 d critical period following incident PE was not increased compared to patients with incident DVT, as long as patients initiated and persisted with anticoagulant therapy. Increased focus on antithrombotic therapy in PE patients and reasons for early therapy discontinuation may be warranted. PMID- 26828387 TI - MicroRNA-221 sponge therapy attenuates neointimal hyperplasia and improves blood flows in vein grafts. AB - BACKGROUND: Vein graft failure due to neointimal hyperplasia remains an important and unresolved problem of cardiovascular surgery. MicroRNA-221 (miR-221) has been shown to play a major role in regulating vascular smooth muscle cell (VSMC) proliferation and phenotype transformation. Thus, the purpose of this study is to determine whether adenovirus mediated miR-221 sponge gene therapy could inhibit vein graft neointimal hyperplasia. METHODS: Adenovirus encoding miR-221 sponge (Ad-miR-221-SP) was used to inhibit VSMC proliferation in vitro and neointimal formation in vivo. Expression of miRNA-221 was evaluated in cultured VSMC and in rat vein graft models following transduction with Ad-miR-221-SP, Ad-Control-SP (without miR-221 antisense binding sites), or Ad-GFP (control). To accelerate the transfer of miR-221 sponge gene to the vein grafts, 20% poloxamer F-127 gel was used to extend virus contact time and 0.25% trypsin to increase virus penetration. RESULTS: miR-221 sponges can significantly decrease the expression of miR-221 and proliferation in cultured VSMC. Cellular proliferation rates were significantly reduced in miR-221 sponge treated grafts as compared with controls at 6 weeks after bypass surgery (19.8% versus 43.6%, P=0.0028). miR-221 sponge gene transfer reduced the neointimal area (210.75 +/- 24.13 versus 67.01 +/- 12.02, P<0.0001), neointimal thickness (171.86 +/- 27.87 versus 64.13 +/- 16.23, P<0.0001) and neointima/media ratio (0.74 +/- 0.21 versus 1.95 +/- 0.25, P<0.0001) in vein grafts versus controls. miR-21 sponge treatment was also improved hemodynamics in vein grafts. We have further identified that p27 (Kip1) is a potential target gene of miR-221 in vein grafts. CONCLUSION: miR-221 sponge therapy can significantly reduce miR-221 activity and inhibit neointimal hyperplasia in vein grafts. Locally adventitial delivery of adenoviruses mediated miRNA sponges may be promising gene therapies to prevent vein graft failure. PMID- 26828388 TI - Correlation of Clinical Outcomes with Quantitative Polymerase Chain Reaction DNA Copy Number in Patients with Acute Retinal Necrosis. AB - PURPOSE: To correlate visual acuity outcomes and clinical features with quantitative PCR DNA copy number in patients with acute retinal necrosis (ARN). METHODS: Retrospective, consecutive case series. RESULTS: In total, 14 eyes of 13 patients were diagnosed with ARN, based on the American Uveitis Society criteria, and were followed for a mean of 324.5 days (median 250.5 days, SD +/- 214 days). Anterior chamber fluid analyzed by quantitative PCR identified viral DNA in 11 of 14 eyes (78.5%). Varicella zoster virus (VZV) was identified in seven eyes (50%) and herpes simplex virus (HSV) in four eyes (28.5%). Mean DNA copy number was 7.9 * 106/mL (median 2.10 * 106/mL, range: 0-5.60 * 107/mL). Eyes with quantitative PCR DNA copy number of >=5.0 * 106/mL (n = 6 eyes) had worse baseline visual acuity (logMAR 1.48 +/- 0.71 vs 0.94 +/- 0.76, p = 0.196) and final visual acuity (logMAR 2.10 +/- 0.60 vs 0.82 +/- 0.81, p = 0.007) compared with patients with a DNA copy number <5.0 * 106/mL (n = 8 eyes). Patients with a DNA copy number of >=5.0 * 106/mL were more likely to have at least 5 clock hours of retinitis on funduscopic exam (p = 0.03) and developed retinal detachment more frequently (p = 0.08). CONCLUSIONS: Quantitative DNA copy number of >=5.0 * 106/mL is associated with more extensive retinitis, worse visual acuity, and development of retinal detachment in patients with acute retinal necrosis. PMID- 26828389 TI - Serum amyloid A in marine bivalves: An acute phase and innate immunity protein. AB - Serum amyloid A (SAA) is among the most potent acute phase proteins (APP) in vertebrates. After injury, its early expression can dramatically increase to promote the recruitment of immuno-competent cells, expression of pro-inflammatory proteins and the activation of the innate immune defences. Although APP have been studied in many vertebrates, only recently their search was extended to invertebrates and the finding of SAA-like molecules has opened new questions on the immune-regulatory functions of these soluble proteins in the animal kingdom. Taking advantage of the considerable amount of genomic and transcriptomic data currently available, we retrieved 51 SAA-like proteins in several protostome taxa comprising 21 marine bivalve species and basal metazoans. In addition to vertebrate-like SAAs, we identified a second protein type with peculiar features. In the bivalves Crassostrea gigas and Mytilus galloprovincialis, both digital expression analysis and qPCR data indicated an induction of the classical SAA after bacterial challenge. PMID- 26828390 TI - WSV399, a viral tegument protein, interacts with the shrimp protein PmVRP15 to facilitate viral trafficking and assembly. AB - Viral responsive protein 15 (PmVRP15) has been identified as a highly up regulated gene in the hemocyte of white spot syndrome virus (WSSV)-infected shrimp Penaeus monodon. However, the function of PmVRP15 in host-viral interaction was still unclear. To elucidate PmVRP15 function, the interacting partner of PmVRP15 from WSSV was screened by yeast two-hybrid assay and then confirmed by co-immunoprecipitation (Co-IP). Only WSV399 protein was identified as a PmVRP15 binding protein; however, the function of WSV399 has not been characterized. Localization of WSV399 on the WSSV virion was revealed by immunoblotting analysis (in vitro) and immunoelectron microscopy (in vivo). The results showed that WSV399 is a structural protein of the WSSV virion and is particularly located on the tegument. Gene silencing of wsv399 in WSSV-infected shrimp reduced the percentage of cumulative mortality by 74%, although the expression level of a viral replication marker gene, vp28, was not changed suggesting that WSV399 might not involved in viral replication but viral assembly. Because it has already been known that tegument proteins function in capsid transport during viral trafficking and assembly, interaction between PmVRP15 on hemocyte nuclear membrane and the WSV399 viral tegument protein suggests that PmVRP15 might be required for trafficking and assembly of WSSV during infection. PMID- 26828391 TI - Immunity to gastrointestinal microparasites of fish. AB - Fish intestinal parasites cause direct mortalities and also morbidity, poor growth, higher susceptibility to opportunistic pathogens and lower resistance to stress. This review is focused on microscopic parasites (Protozoa and Metazoa) that invade the gastrointestinal tract of fish. Intracellular parasites (mainly Microsporidia and Apicomplexa) evoke almost no host immune reaction while they are concealed in the cytoplasmic and nuclear compartments, and can even use fish cells (macrophages) as Trojan horses to spread in the host. Inflammatory reaction only appears when the parasite bursts infected cells. Immunity against extracellular parasites is depicted for the myxozoans Ceratonova shasta and Enteromyxum spp. The cellular and humoral innate responses and the production of antibodies are crucial for resolving some of these myxozoonoses, but an excessive inflammatory reaction (concerted by cytokines) can become a fatal pathophysiological consequence. The local immune response plays a key role, with numerous genes more strongly regulated in the intestine than at lymphohaematopoietic organs. PMID- 26828392 TI - Induction of interferon and cell death in response to cytosolic DNA in chicken macrophages. AB - Responses to cytosolic DNA can protect against both infectious organisms and the mutagenic effect of DNA integration. Recognition of invading DNA is likely to be fundamental to eukaryotic cellular life, but has been described only in mammals. Introduction of DNA into chicken macrophages induced type I interferon mRNA via a pathway conserved with mammals, requiring the receptor cGAS and the signalling protein STING. A second pathway of cytosolic DNA recognition in mammalian macrophages, initiated by absent in melanoma 2 (AIM2), results in rapid inflammasome-mediated pyroptotic cell death. AIM2 is restricted to mammals. Nevertheless, chicken macrophages underwent lytic cell death within 15 min of DNA transfection. The mouse AIM2-mediated response requires double stranded DNA, but chicken cell death was maintained with denatured DNA. This appears to be a novel form of rapid necrotic cell death, which we propose is an ancient response rendered redundant in mammalian macrophages by the appearance of the AIM2 inflammasome. The retention of these cytosolic DNA responses through evolution, with both conserved and non-conserved mechanisms, suggests a fundamental importance in cellular defence. PMID- 26828393 TI - Identification and functional characterization of TNF receptor associated factor 3 in the sea cucumber Apostichopus japonicus. AB - TNF receptor associated factors (TRAFs) are a family of proteins primarily involved in both adaptive and innate immunity. In this study, we identified a novel TRAF3 gene in Apostichopus japonicus by transcriptome sequencing and RACE approaches (designated as AjTRAF3). The full-length of AjTRAF3 was of 2796 bp including a 5' untranslated region (UTR) of 83 bp, a 3' UTR of 1066 bp and a putative open reading frame of 1647 bp encoding a polypeptide of 548 amino acid residues. The representative domains such as a RING finger domain (residues 54 96), two TRAF domains with zinc finger structure (residues 141-228), a coiled coil and a meprin and TRAF homology (MATH) domain (residues 396-522) were all detected in the deduced amino acids of AjTRAF3. AjTRAF3 was ubiquitously expressed in all examined tissues with predominant expression in the body wall and slightly weaker in intestine, respiratory tree, tube feet, coelomocytes and longitudinal muscle. Time-course expression analysis in coelomocytes revealed that AjTRAF3 was significantly depressed towards Vibrio splendidus infection with a 0.20-fold decrease at 12 h, compared to control levels. AjTRAF3 silencing could elevate intracellular ROS levels by 2.08-fold and 2.09-fold compared to each control group in vitro and in vivo, respectively. Taken together, all these results suggested that AjTRAF3 may play a crucial role in the processes of anti bacteria response in sea cucumber through regulating ROS production. PMID- 26828395 TI - Outcomes of a Character Strengths-Based Intervention on Self-Esteem and Self Efficacy of Psychiatrically Hospitalized Youths. AB - OBJECTIVE: Mental health treatment approaches based on character strengths can be used to complement the traditional focus on functional impairment. The study tested use of a character strengths-based intervention to enhance the self-esteem and self-efficacy of psychiatrically hospitalized youths. METHODS: Eighty-one hospitalized adolescents were randomly assigned to intervention or comparison groups. The intervention used the Values in Action Inventory of Strengths for Youth to discover character strengths and incorporate them into coping skills. Self-efficacy and self-esteem were measured at baseline, postintervention, two weeks, and three months. RESULTS: Self-esteem and self-efficacy initially increased in both groups, but only the intervention group showed sustained improvement. The intervention was associated with increased self-efficacy at two weeks and increased self-efficacy and self-esteem at three months. CONCLUSIONS: A brief, easily administered character strengths-based intervention may be an adjunctive tool in the treatment of psychiatrically hospitalized youths. PMID- 26828394 TI - Outcomes and reflections on a consensus-building workshop for developing a spinal cord injury-related chronic pain research agenda. AB - : Context/ Objective: Chronic pain following spinal cord injury (SCI) is a prevalent secondary health condition that significantly impacts quality of life (QoL). Although growing, the number of available effective pain management approaches for SCI is limited. Recognizing the need to "kick-start" activity on this topic, a consensus-building workshop on developing a research agenda for SCI related chronic pain was held in 2006 with an expert panel. The present paper describes the processes of the consensus-workshop and its associated outcomes towards advancing the research agenda for SCI-related pain in Canada. A commentary on the current state of knowledge regarding SCI-related pain is also provided. METHODS: Thirty-nine stakeholders (researchers, clinicians, policy makers, SCI advocates, and people with SCI) attended the consensus-workshop. A modified Delphi approach was employed to gain consensus on identifying the top five SCI pain research priorities for improving QoL post-SCI. As well, project planning along with infrastructure support opportunities were discussed. RESULTS: The top five pain research priorities were: 1) pain management and treatment; 2) measurement tools; 3) health services policy and advocacy; 4) knowledge transfer; and 5) mechanisms of pain. Recommendations related to the priorities and related resources were generated, and pilot work was initiated. CONCLUSIONS: The consensus workshop provided an initial roadmap for research on SCI-related chronic pain, and supported five pilot projects on the identified priorities. Reflections on the current research landscape in Canada and abroad suggest increased activity towards addressing pain post-SCI but evidence-based approaches are still lacking. PMID- 26828396 TI - Implementation Status of Assisted Outpatient Treatment Programs: A National Survey. AB - OBJECTIVE: The authors' objective was to determine how assisted outpatient treatment (AOT) has been implemented in actual practice in the 45 states with AOT statutes. METHODS: A national survey of AOT programs was conducted to examine the extent to which AOT programs have been implemented and variations in implementation models. RESULTS: Although 45 states have current AOT statutes, the most active programs were identified in 20 states. These programs varied considerably in style of implementation, criteria applied, agency responsible, use of a treatment plan, monitoring procedures, and numbers of participants involved. Three implementation models were identified: community gateway, hospital transition, and surveillance (or safety net). Common problems included inadequate resources, lack of enforcement power, inconsistent monitoring, and weakness of interagency collaboration. CONCLUSIONS: AOT is a widely applied and much-discussed mechanism for providing treatment to individuals with serious mental illnesses nationally. The uneven implementation of AOT programs within and across states highlights the ambivalence in the community, by judicial officials, and by mental health clinicians about the role and scope of AOT and the difficulties of implementation under existing funding constraints and statutory limitations. PMID- 26828397 TI - An Emergency Department Intervention and Follow-Up to Reduce Suicide Risk in the VA: Acceptability and Effectiveness. AB - OBJECTIVE: Emergency departments (EDs) are often the primary contact point for suicidal individuals. The post-ED visit period is a high suicide risk time. To address the need for support during this time, a novel intervention was implemented in five Department of Veterans Affairs medical center EDs. The intervention combined the Safety Planning Intervention (SPI) with structured follow-up and monitoring (SFU) by telephone for suicidal individuals who did not require hospitalization. This study assessed the intervention's acceptability and perceived usefulness. METHODS: A selected sample of 100 intervention participants completed a semistructured interview consisting of open-ended questions about the intervention's acceptability, usefulness, and helpfulness. Satisfaction with the SPI and SFU was separately evaluated. RESULTS: Nearly all participants found the SAFE VET intervention to be acceptable, reporting that it was helpful in preventing further suicidal behavior and fostering treatment engagement. CONCLUSIONS: The SAFE VET intervention showed promise as an ED intervention for suicidal patients. PMID- 26828398 TI - Use of Mental Health Services by Youths and Young Adults Before and During Correctional Custody: A Population-Based Study. AB - OBJECTIVE: The authors measured use of mental health services among young people before and during incarceration. METHODS: Administrative data were used to describe mental health services received by 13,919 youths and young adults (ages 12-24) while incarcerated in Ontario, Canada, correctional centers (physician visits, April 1, 2010-March 31, 2012) and, for a subset of the population, during the five years prior to incarceration. RESULTS: Forty-two percent had a mental health-related visit during incarceration. Thirty-five percent had no mental health contact for five years before the beginning of the correctional episode. Forty percent of individuals with schizophrenia had a psychiatric hospitalization in the year before entering custody. CONCLUSIONS: For one-third of young people with a mental health visit while incarcerated, the visit was the first mental health contact in at least five years. Yet high use of psychiatric services before entering custody among individuals with schizophrenia may indicate gaps in continuity of mental health care. PMID- 26828399 TI - Permanent Supportive Housing for Transition-Age Youths: Service Costs and Fidelity to the Housing First Model. AB - OBJECTIVE: Permanent supportive housing (PSH) programs are being implemented nationally and on a large scale. However, little is known about PSH for transition-age youths (ages 18 to 24). This study estimated health services costs associated with participation in PSH among youths and examined the relationship between fidelity to the Housing First model and health service outcomes. METHODS: Administrative data were used in a quasi-experimental, difference-in-differences design with a propensity score-matched contemporaneous control group to compare health service costs among 2,609 youths in PSH and 2,609 youths with serious mental illness receiving public mental health services in California from January 1, 2004, through June 30, 2010. Data from a survey of PSH program practices were merged with the administrative data to examine changes in service use among 1,299 youths in 63 PSH programs by level of fidelity to the Housing First model. RESULTS: Total service costs increased by $13,337 among youths in PSH compared with youths in the matched control group. Youths in higher-fidelity programs had larger declines in use of inpatient services and larger increases in outpatient visits compared with youths in lower-fidelity programs. CONCLUSIONS: PSH for youths was associated with substantial increases in costs. Higher-fidelity PSH programs may be more effective than lower-fidelity programs in reducing use of inpatient services and increasing use of outpatient services. As substantial investments are made in PSH for youths, it is imperative that these programs are designed and implemented to maximize their effectiveness and their impact on youth outcomes. PMID- 26828400 TI - Outpatient Mental Health Services in Mozambique: Use and Treatments. AB - To describe current outpatient mental health service use and treatments in Mozambique, the authors reviewed registry entries for 2,071 outpatient psychiatric visits at the Beira Central Hospital in Sofala Province from January 2012 to September 2014. Service use was most common for schizophrenia, followed by epilepsy, delirium, and organic behavioral disorders. Only 3% of consultations for schizophrenia were first-visit patients. Treatment seeking among women was more likely for mood and neurotic disorders and less likely for substance use disorders and epilepsy. First-generation antipsychotics, most often paired with promethazine, dominated treatment regimens. Evidence-based reforms are needed to improve identification of mood disorders and broaden care beyond severe mental disorders. PMID- 26828401 TI - Expansive Phenotypic Landscape of Botrytis cinerea Shows Differential Contribution of Genetic Diversity and Plasticity. AB - The modern evolutionary synthesis suggests that both environmental variation and genetic diversity are critical determinants of pathogen success. However, the relative contribution of these two sources of variation is not routinely measured. To estimate the relative contribution of plasticity and genetic diversity for virulence-associated phenotypes in a generalist plant pathogen, we grew a population of 15 isolates of Botrytis cinerea from throughout the world, under a variety of in vitro and in planta conditions. Under in planta conditions, phenotypic differences between the isolates were determined by the combination of genotypic variation within the pathogen and environmental variation. In contrast, phenotypic differences between the isolates under in vitro conditions were predominantly determined by genetic variation in the pathogen. Using a correlation network approach, we link the phenotypic variation under in vitro experimental conditions to phenotypic variation during plant infection. This study indicates that there is a high level of phenotypic variation within B. cinerea that is controlled by a mixture of genetic variation, environment, and genotype * environment. This argues that future experiments into the pathogenicity of B. cinerea must account for the genetic and environmental variation within the pathogen to better sample the potential phenotypic space of the pathogen. PMID- 26828402 TI - The MU Subunit of Arabidopsis Adaptor Protein-2 Is Involved in Effector-Triggered Immunity Mediated by Membrane-Localized Resistance Proteins. AB - Endocytosis has been suggested to be important in the cellular processes of plant immune responses. However, our understanding of its role during effector triggered immunity (ETI) is still limited. We have previously shown that plant endocytosis, especially clathrin-coated vesicle formation at the plasma membrane, is mediated by the adaptor protein-2 (AP-2) complex and that loss of the MU subunit of AP-2 (AP2M) affects plant growth and floral organ development. Here, we report that AP2M is required for full-strength ETI mediated by the disease resistance (R) genes RPM1 and RPS2 in Arabidopsis. Reduced ETI was observed in an ap2m mutant plant, measured by growth of Pseudomonas syringae pv. tomato DC3000 strains carrying the corresponding effector genes avrRpm1 or avrRpt2 and by hypersensitive cell death response and defense gene expression triggered by these strains. In contrast, RPS4-mediated ETI and its associated immune responses were not affected by the ap2m mutation. While RPM1 and RPS2 are localized to the plasma membrane, RPS4 is localized to the cytoplasm and nucleus. Our results suggest that AP2M is involved in ETI mediated by plasma membrane-localized R proteins, possibly by mediating endocytosis of the immune receptor complex components from the plasma membrane. PMID- 26828403 TI - Gene editing in veterinary pathophysiology. PMID- 26828404 TI - Calcium urolithiasis in a breeding population of southern flounder (Paralichthys lethostigma) housed in a low salinity environment. PMID- 26828405 TI - Reduction of the plastidial phosphorylase in potato (Solanum tuberosum L.) reveals impact on storage starch structure during growth at low temperature. AB - Tubers of potato (Solanum tuberosum L.), one of the most important crops, are a prominent example for an efficient production of storage starch. Nevertheless, the synthesis of this storage starch is not completely understood. The plastidial phosphorylase (Pho1; EC 2.4.1.1) catalyzes the reversible transfer of glucosyl residues from glucose-1-phosphate to the non-reducing end of alpha-glucans with the release of orthophosphate. Thus, the enzyme is in principle able to act during starch synthesis. However, so far under normal growth conditions no alterations in tuber starch metabolism were observed. Based on analyses of other species and also from in vitro experiments with potato tuber slices it was supposed, that Pho1 has a stronger impact on starch metabolism, when plants grow under low temperature conditions. Therefore, we analyzed the starch content, granule size, as well as the internal structure of starch granules isolated from potato plants grown under low temperatures. Besides wild type, transgenic potato plants with a strong reduction in the Pho1 activity were analyzed. No significant alterations in starch content and granule size were detected. In contrast, when plants were cultivated at low temperatures the chain length distributions of the starch granules were altered. Thus, the granules contained more short glucan chains. That was not observed in the transgenic plants, revealing that Pho1 in wild type is involved in the formation of the short glucan chains, at least at low temperatures. PMID- 26828406 TI - Melatonin-induced CBF/DREB1s are essential for diurnal change of disease resistance and CCA1 expression in Arabidopsis. AB - Melatonin (N-acetyl-5-methoxytryptamine) is an important regulator of circadian rhythms and immunity in animals. However, the diurnal changes of endogenous melatonin and melatonin-mediated diurnal change of downstream responses remain unclear in Arabidopsis. Using the publicly available microarray data, we found that the transcript levels of two melatonin synthesis genes (serotonin N acetyltransferase (SNAT) and caffeate O-methyltransferase (COMT)) and endogenous melatonin level were regulated by diurnal cycles, with different magnitudes of change. Moreover, the transcripts of C-repeat-binding factors (CBFs)/Drought response element Binding 1 factors (DREB1s) were co-regulated by exogenous melatonin and diurnal changes, indicating the possible correlation among clock, endogenous melatonin level and AtCBFs expressions. Interestingly, diurnal change of plant immunity against Pst DC3000 and CIRCADIANCLOCK ASSOCIATED 1 (CCA1) expression were largely lost in AtCBFs knockdown line-amiR-1. Taken together, this study identifies the molecular pathway underlying the diurnal changes of immunity in Arabidopsis. Notably, the diurnal changes of endogenous melatonin may regulate corresponding changes of AtCBF/DREB1s expression and their underlying diurnal cycle of plant immunity and AtCCA1. PMID- 26828407 TI - Transcriptome analysis of the Taxodium 'Zhongshanshan 405' roots in response to salinity stress. AB - Taxodium 'Zhongshanshan' is an interspecies hybrid of Taxodium distichum and Taxodium mucronatum, and has been widely planted in southeastern China. It has great ecological and economic potential. However, the scant genomic resources in genus Taxodium have greatly hindered further exploration of its underlying salinity-tolerance mechanism. To understand the genetic basis of its salt tolerance, high-throughput sequencing of mRNA (RNA-Seq) was used to analyze transcriptome changes of 'Zhongshanshan 405' clone roots treated with NaCl stress. After de novo assembly, 70,312 unigenes were achieved, and 41,059 of them were annotated. 9038 differentially expressed genes (DEGs) were identified among the treatments, and 7959 DEGs were found between salt-stressed roots and control, with 489 up-regulated and 570 down-regulated shared by all of the treatments. Genes related to transport, signal transductions as well as undescribed transcripts were among those DEGs in response to salt stress. Gene ontology classification analysis revealed that salt stress-related categories including 'oxidoreductase activity', 'metal ion binding', and 'membrane' were highly enriched among these DEGs. Moreover, the gene expression pattern of 12 unigenes revealed by quantitative real-time polymerase chain reaction (qRT-PCR) confirmed the RNA-Seq data. Our study not only provided the large-scale assessment of transcriptome resources of Taxodium but also guidelines for probing the molecular mechanism underlying 'Zhongshanshan' salt tolerance. PMID- 26828409 TI - Park availability and physical activity, TV time, and overweight and obesity among women: Findings from Australia and the United States. AB - This study examined relationships between three measures of park availability and self-reported physical activity (PA), television viewing (TV) time, and overweight/obesity among women from Australia and the United States. Having more parks near home was the only measure of park availability associated with an outcome. Australian women (n=1848) with more parks near home had higher odds of meeting PA recommendations and lower odds of being overweight/obese. In the US sample (n=489), women with more parks near home had lower odds of watching >4h TV per day. A greater number of parks near home was associated with lower BMI among both Australian and US women. Evidence across diverse contexts provides support to improve park availability to promote PA and other health behaviors. PMID- 26828408 TI - Effects of unilateral stroke on multi-finger synergies and their feed-forward adjustments. AB - We explored the changes in multi-finger synergies in patients after a single cortical stroke with mild motor impairments. We hypothesized that both synergy indices and anticipatory synergy adjustments prior to the initiation of a self paced quick action would be diminished in the patients compared to age-matched controls. The patients with history of cortical stroke, and age-matched controls (n=12 in each group) performed one-finger and multi-finger accurate force production tasks involving both steady-state and quick force pulse production. Finger interdependence (enslaving) and multi-finger synergies stabilizing total force were quantified. The stroke patients showed lower maximal finger forces, in particular in the contralesional hand, which also showed increased enslaving indices. Multi-finger synergies during steady-state force production were, however, unchanged after stroke. In contrast, a drop in the synergy index prior to the force pulse generation was significantly delayed in the stroke patients. Our results show that mild cortical stroke leads to no significant changes in multifinger synergies, but there is impairment in feed-forward adjustments of the synergies prior to a quick action, a drop in the maximal force production, and an increase in enslaving. We conclude that studies of synergies reveal two aspects of synergic control differentially affected by cortical stroke. PMID- 26828411 TI - Nonpharmacologic Management Strategies in ALS #300. PMID- 26828410 TI - High School Football Injury Rates and Services by Athletic Trainer Employment Status. AB - CONTEXT: Reported injury rates and services in sports injury surveillance may be influenced by the employment setting of the certified athletic trainers (ATs) reporting these data. OBJECTIVE: To determine whether injury rates and the average number of AT services per injury in high school football varied by AT employment status. DESIGN: Cross-sectional study. SETTING: We used data from the National Athletic Treatment, Injury and Outcomes Network and surveyed ATs about their employment setting. PATIENTS OR OTHER PARTICIPANTS: Forty-four responding ATs (37.9% of all National Athletic Treatment, Injury and Outcomes Network participants) worked at high schools with football programs and were included in this study. Fourteen ATs were full-time employees of the high school, and 30 ATs were employed as outreach ATs (i.e., full-time and part-time ATs from nearby clinics, hospitals, and graduate school programs). MAIN OUTCOME MEASURE(S): We calculated injury rates per 1000 athlete-exposures and average number of AT services per injury. RESULTS: Reported injury rates and services per injury were greater among full-time school employees compared with outreach ATs. However, injury rates did not differ when restricted to time-loss injuries only. CONCLUSIONS: Our findings suggest that ATs who are full-time school employees may be able to identify and care for more patients with injuries. PMID- 26828412 TI - Class I Hydrophobin Vmh2 Adopts Atypical Mechanisms to Self-Assemble into Functional Amyloid Fibrils. AB - Hydrophobins are fungal proteins whose functions are mainly based on their capability to self-assemble into amphiphilic films at hydrophobic-hydrophilic interfaces (HHI). It is widely accepted that class I hydrophobins form amyloid like structures, named rodlets, which are hundreds of nanometers long, packed into ordered lateral assemblies and do not exhibit an overall helical structure. We studied the self-assembly of the Class I hydrophobin Vmh2 from Pleurotus ostreatus in aqueous solutions by dynamic light scattering (DLS), thioflavin T (ThT), fluorescence assay, circular dichroism (CD), cryogenic trasmission electron microscopy (cryo-TEM), and TEM. Vmh2 does not form fibrillar aggregates at HHI. It exhibits spherical and fibrillar assemblies whose ratio depends on the protein concentration when freshly solubilized at pH >= 7. Moreover, it spontaneously self-assembles into isolated, micrometer long, and twisted amyloid fibrils, observed for the first time in fungal hydrophobins. This process is promoted by acidic pH, temperature, and Ca(2+) ions. A model of self-assembly into amyloid-like structures has been proposed. PMID- 26828413 TI - Synthesis and Cytoxicity of Sempervirine and Analogues. AB - Sempervirine and analogues were synthesized using a route featuring Sonogashira and Larock Pd-catalyzed reactions. Structure-activity relationships were investigated using three human cancer cell lines. 10-Fluorosempervirine is the most potently cytotoxic member of the family yet described. PMID- 26828414 TI - Dopamine/Silica Nanoparticle Assembled, Microscale Porous Structure for Versatile Superamphiphobic Coating. AB - Artificial superamphiphobic surfaces, which could repel both water and low surface tension organic liquids, have been limited to particular kinds of materials or surfaces thus far. In this work, a kind of microscale porous coating was developed. Taking dopamine and hydrophilic fumed silica nanoparticles as initial building blocks, microscale porous coating was constructed via ice templation. Polydopamine bound silica nanoparticles together to form a porous structure network and rendered the coating to have potential for further postfunctionalization. After two-step CVD, the microscale porous coating changes from superhydrophilic to superamphiphobic, exhibiting super-repellency to droplets with surface tension of 73-23 mN/m. The influences of concentration of initial dopamine, hydrophilic fumed silica nanoparticles, and dry conditions on the formation of the porous structure have been studied to optimize the conditions. Coatings with different pore sizes and pore heights have been fabricated to discover the relationship between the structure parameters and the repellency of the porous coatings. Only with optimal pore size and pore height can the porous coating display superamphiphobicity. Compared with nanoscale, the microscale structure favors the achievement of superamphiphobicity. Given the outstanding adhesive ability of polydopamine, the superamphiphobic coatings have been successfully applied to various materials including artificial materials and natural materials. PMID- 26828415 TI - Composite Nanoformulation Therapeutics for Long-Term Ocular Delivery of Macromolecules. AB - The purpose of this investigation is to design and synthesize novel pentablock (PB) copolymer (PB-1: PCL-PLA-PEG-PLA-PCL) based nanoformulations suspended in a thermosensitive gelling copolymer (PB-2: mPEG-PCL-PLA-PCL-PEGm) termed as composite nanoformulation. The composite nanoformulation was prepared to provide a sustained delivery of macromolecules over a longer duration with negligible burst release effect. The delivery system was designed to be utilized for the treatment of posterior segment ocular diseases such as age-related (wet) macular degeneration, diabetic retinopathy, and diabetic macular edema. The novel PB copolymers were characterized for their functional groups by Fourier transform infrared spectroscopy, molecular weight and purity by (1)H NMR spectroscopy, and gel permeation chromatography. X-ray diffraction analysis was used to determine the crystallinity of copolymers. The size distribution of PB-1 nanoparticles (NPs) prepared using emulsification-solvent evaporation method was found to be ~150 nm analyzed by nanoparticle tracking analysis. The % encapsulation efficiency and % drug loading were found to be 66.64% w/w +/- 1.75 and 18.17% w/w +/- 0.39, respectively, (n = 3). Different weight percentages (15 and 20 wt %) of the PB-2 copolymer have been utilized for in vitro release studies of IgG-Fab from composite nanoformulation. A negligible burst release with continuous near zero-order release has been observed from the composite nanoformulation analyzed up to 80 days. In vitro cell viability and biocompatibility studies performed on ocular (human corneal epithelial and retinal pigment epithelium) and mouse macrophage (RAW 264.7) cell lines showed that the synthesized PB copolymer based composite nanoformulations were safe for clinical applications. On the basis of the results observed, it is concluded that PB copolymer based composite nanoformulations can serve as a platform for ocular delivery of therapeutic proteins. In addition, the composite nanoformulation may provide minimal side effects associated with frequent intravitreal injections. PMID- 26828416 TI - Ultrasensitive Speciation Analysis of Mercury in Rice by Headspace Solid Phase Microextraction Using Porous Carbons and Gas Chromatography-Dielectric Barrier Discharge Optical Emission Spectrometry. AB - Rice consumption is a primary pathway for human methylmercury (MeHg) exposure in inland mercury mining areas of Asia. In addition, the use of iodomethane, a common fumigant that significantly accelerates the methylation of mercury in soil under sunlight, could increase the MeHg exposure from rice. Conventional hyphenated techniques used for mercury speciation analysis are usually too costly for most developing countries. Consequently, there is an increased interest in the development of sensitive and inexpensive methods for the speciation of mercury in rice. In this work, gas chromatography (GC) coupled to dielectric barrier discharge optical emission spectrometry (DBD-OES) was developed for the speciation analysis of mercury in rice. Prior to GC-DBD-OES analysis, mercury species were derivatized to their volatile species with NaBPh4 and preconcentrated by headspace solid phase microextraction using porous carbons. Limits of detection of 0.5 MUg kg(-1) (0.16 ng), 0.75 MUg kg(-1) (0.24 ng), and 1.0 MUg kg(-1) (0.34 ng) were obtained for Hg(2+), CH3Hg(+), and CH3CH2Hg(+), respectively, with relative standard deviations (RSDs) better than 5.2% and 6.8% for one fiber or fiber-to-fiber mode, respectively. Recoveries of 90-105% were obtained for the rice samples, demonstrating the applicability of the proposed technique. Owing to the small size, low power, and low gas consumption of DBD-OES as well as efficient extraction of mercury species by porous carbons headspace solid phase micro-extraction, the proposed technique provides several advantages including compactness, cost-effectiveness, and potential to couple with miniature GC to accomplish the field speciation of mercury in rice compared to conventional hyphenated techniques. PMID- 26828417 TI - Nonlinear photomechanics of nematic networks: upscaling microscopic behaviour to macroscopic deformation. AB - A liquid crystal network whose chromophores are functionalized by photochromic dye exhibits light-induced mechanical behaviour. As a result, the micro-scaled thermotropic traits of the network and the macroscopic phase behaviour are both influenced as light alternates the shape of the dyes. In this paper, we present an analysis of this photomechanical behaviour based on the proposed multiscale framework, which incorporates the molecular details of microstate evolution into a continuum-based understanding. The effects of trans-to-cis photoisomerization driven by actinic light irradiation are first examined using molecular dynamics simulations, and are compared against the predictions of the classical dilution model; this reveals certain characteristics of mesogenic interaction upon isomerization, followed by changes in the polymeric structure. We then upscale the thermotropic phase-related information with the aid of a nonlinear finite element analysis; macroscopic deflection with respect to the wide ranges of temperature and actinic light intensity are thereby examined, which reveals that the classical model underestimates the true deformation. This work therefore provides measures for analysing photomechanics in general by bridging the gap between the micro- and macro-scales. PMID- 26828418 TI - TruSPAdes: barcode assembly of TruSeq synthetic long reads. AB - The recently introduced TruSeq synthetic long read (TSLR) technology generates long and accurate virtual reads from an assembly of barcoded pools of short reads. The TSLR method provides an attractive alternative to existing sequencing platforms that generate long but inaccurate reads. We describe the truSPAdes algorithm (http://bioinf.spbau.ru/spades) for TSLR assembly and show that it results in a dramatic improvement in the quality of metagenomics assemblies. PMID- 26828419 TI - Quantification of private information leakage from phenotype-genotype data: linking attacks. AB - Studies on genomic privacy have traditionally focused on identifying individuals using DNA variants. In contrast, molecular phenotype data, such as gene expression levels, are generally assumed to be free of such identifying information. Although there is no explicit genotypic information in phenotype data, adversaries can statistically link phenotypes to genotypes using publicly available genotype-phenotype correlations such as expression quantitative trait loci (eQTLs). This linking can be accurate when high-dimensional data (i.e., many expression levels) are used, and the resulting links can then reveal sensitive information (for example, the fact that an individual has cancer). Here we develop frameworks for quantifying the leakage of characterizing information from phenotype data sets. These frameworks can be used to estimate the leakage from large data sets before release. We also present a general three-step procedure for practically instantiating linking attacks and a specific attack using outlier gene expression levels that is simple yet accurate. Finally, we describe the effectiveness of this outlier attack under different scenarios. PMID- 26828420 TI - Tandem Long Distance Chain-Walking/Cyclization via RuH2(CO)(PPh3)3/Bronsted Acid Catalysis: Entry to Aromatic Oxazaheterocycles. AB - A novel route to 1,3-oxazaheterocycles based on cooperative Ru-H/Bronsted acid catalysis is reported. The use of the commercially available RuH2(CO)(PPh3)3 complex allows for an efficient long distance chain-walking process while the Bronsted acid is responsible for generation of an electrophilic iminium ion which is trapped intramolecularly by an alcohol moiety. The alcohol, besides its nucleophilic function, also plays an important role in the stabilization of the Ru catalyst. PMID- 26828422 TI - Mortality Among Centenarians in the United States, 2000-2014. AB - KEY FINDINGS: Data from the National Vital Statistics System, Mortality. Death rates for centenarians increased from 2000 through 2008 and then decreased through 2014 for both males and females. Death rates for centenarians increased from 2000 through 2006 for the Hispanic population and from 2000 through 2008 for the non- Hispanic white and black populations, and subsequently decreased through 2014 for all racial and ethnic groups examined. The top five causes of death among centenarians in 2014 were heart disease, Alzheimer's disease, stroke, cancer, and influenza and pneumonia. Death rates for Alzheimer's disease increased 119% between 2000 and 2014 among centenarians. PMID- 26828421 TI - Modeling of breath methane concentration profiles during exercise on an ergometer. AB - We develop a simple three compartment model based on mass balance equations which quantitatively describes the dynamics of breath methane concentration profiles during exercise on an ergometer. With the help of this model it is possible to estimate the endogenous production rate of methane in the large intestine by measuring breath gas concentrations of methane. PMID- 26828423 TI - Delivering neurocritical care in resource-challenged environments. AB - PURPOSE OF REVIEW: Resource-challenged environments of low and middle-income countries face a significant burden of neurocritical illness. This review attempts to elaborate on the multiple barriers to delivering neurocritical care in these settings and the possible solutions to overcome such barriers. RECENT FINDINGS: Epidemiology of neurocritical illness appears to have changed over time in low and middle-income countries. In addition to neuro-infection, noncommunicable neurological illnesses like stroke, traumatic brain injury, and traumatic spinal cord injury pose a significant neurocritical burden in resource limited settings. Many barriers that exist hinder effective delivery of neurocritical care in resource-challenged environments. Very little information exists about the neurocritical care capacity. Research and publications are few. Intensive care unit beds and trained personnel are significantly lacking. Awareness about the risk factors of preventable conditions, including stroke, is lacking. Prehospital care and trauma systems are poorly developed. There should be attempts to leverage neurocritical care in these settings with focus on promoting research, local training, capacity building, preventive measures like vaccination, raising awareness, and developing prehospital care. SUMMARY: Considering the disease burden and potentials to improve outcome, attempts should be made to develop neurocritical care in resource-challenged environments. VIDEO ABSTRACT: http://links.lww.com/COCC/A11. PMID- 26828424 TI - Biomimetic Assembly Lines Producing Natural Product Analogs: Strategies from a Versatile Manifold to Skeletally Diverse Scaffolds. AB - Biosynthetic assembly lines have evolved in nature, adopting divergent processes to produce a vast number of secondary metabolites. Inspired by these biogenetic processes, this account introduces recent investigations by my research group to formulate a synthetic strategy for establishing a biomimetic assembly line. With the aim not only to construct natural product-relevant scaffolds within 5-7 steps, but also to systematically diversify skeletal and stereochemical properties and functional groups, divergent synthetic processes exploiting a versatile manifold have been developed. This approach allows for cost-effective production of skeletally diverse and biologically active natural product analogs inaccessible by other means. Discovery of several lead candidates for a neglected tropical disease is a proof-of-concept of this synthetic approach. PMID- 26828425 TI - Stimulation latency and comparison of cycling regimens in women using sacral neuromodulation. AB - AIMS: In this two-part study, we sought to define how long sacral neuromodulation users with overactive bladder should trial a new setting before attributing symptoms to that setting. Subsequently, we evaluated patient preferences of variable stimulation regimens. METHODS: In the initial phase of this prospective pilot study, participants' devices were turned off and later reactivated; time to symptom recurrence and resolution were recorded. In phase two, participants trialed four settings in a masked fashion with random order. After unmasking, participants chose their preferred setting and were followed 1 year. RESULTS: Twelve subjects completed phase one. With the device off, the mean time to symptom recurrence was 11.25 days. Mean time to symptom regression following reactivation was 6.42 days. Combined, the 90th percentile was 15 days for symptoms to reflect the device's new setting. Among 23 women completing part two, the most popular setting at the time of unmasking was a 1-hr on, 2-hr off cycled setting chosen by 7 (30%) participants. According to published estimates of battery longevity, 14 (61%) participants chose a more energy-conserving setting at the time of unmasking. The mean difference in estimated battery longevity between the chosen and baseline regimens was 14.5 months. These gains diminished in the following year with clinical changes in device settings by patients and providers. CONCLUSIONS: Sacral neuromodulation patients should allow a 2-week trial before attributing symptoms to a new setting. With additional information, many opt for energy-conserving settings. A 1-hr on, 2-hr off regimen warrants further study. Neurourol. Urodynam. 36:486-489, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26828426 TI - Patient-reported outcomes, body composition, and nutrition status in patients with head and neck cancer: Results from an exploratory randomized controlled exercise trial. AB - BACKGROUND: Patients with head and neck cancer experience loss of weight and muscle mass, decreased functioning, malnutrition, depression, and declines in quality of life during and after treatment. The purpose of this exploratory randomized study was to determine the optimal timing for the initiation of a lifestyle and progressive resistance exercise training intervention (during or after radiation therapy), as determined by intervention adherence and by comparing between-group outcomes across 24 weeks. METHODS: Sixty patients with head and neck cancer were randomized to engage in a 12-week lifestyle intervention and progressive resistance-training program either during radiation treatment or immediately after completion. The primary outcome of body composition--specifically, lean body mass, body mass index, and body fat--as well as secondary outcomes of fitness, quality of life, depression, and nutrition status were evaluated. RESULTS: The progressive resistance-training intervention carried out during treatment did not significantly influence the primary outcome of body composition, despite a significant increase in weekly physical activity reported by the intervention group. A small-to-medium intervention effect was noted for some secondary outcomes, including fitness, quality of life, and nutrition status. Regardless of whether patients received the immediate or delayed progressive resistance-training intervention, the analysis revealed a main effect of time on body composition, fitness, quality of life, depression, and nutritional scores. CONCLUSIONS: Although the intervention during treatment did not reduce the loss of lean body mass, delaying the exercise program until after treatment completion was associated with improved intervention adherence, a finding with important clinical implications. PMID- 26828427 TI - Use of Wishart Prior and Simple Extensions for Sparse Precision Matrix Estimation. AB - A conjugate Wishart prior is used to present a simple and rapid procedure for computing the analytic posterior (mode and uncertainty) of the precision matrix elements of a Gaussian distribution. An interpretation of covariance estimates in terms of eigenvalues is presented, along with a simple decision-rule step to improve the performance of the estimation of sparse precision matrices and associated graphs. In this, elements of the estimated precision matrix that are zero or near zero can be detected and shrunk to zero. Simulated data sets are used to compare posterior estimation with decision-rule with two other Wishart based approaches and with graphical lasso. Furthermore, an empirical Bayes procedure is used to select prior hyperparameters in high dimensional cases with extension to sparsity. PMID- 26828428 TI - Population Structure of Peronospora effusa in the Southwestern United States. AB - Peronospora effusa is an obligate pathogen that causes downy mildew on spinach and is considered the most economically important disease of spinach. The objective of the current research was to assess genetic diversity of known historical races and isolates collected in 2014 from production fields in Yuma, Arizona and Salinas Valley, California. Candidate neutral single nucleotide polymorphisms (SNPs) were identified by comparing sequence data from reference isolates of known races of the pathogen collected in 2009 and 2010. Genotypes were assessed using targeted sequencing on genomic DNA extracted directly from infected plant tissue. Genotyping 26 historical and 167 contemporary samples at 46 SNP loci revealed 82 unique multi-locus genotypes. The unique genotypes clustered into five groups and the majority of isolates collected in 2014 were genetically closely related, regardless of source location. The historical samples, representing several races, showed greater genetic differentiation. Overall, the SNP data indicate much of the genotypic variation found within fields was produced during asexual development, whereas overall genetic diversity may be influenced by sexual recombination on broader geographical and temporal scales. PMID- 26828429 TI - Quantifying Clonal and Subclonal Passenger Mutations in Cancer Evolution. AB - The vast majority of mutations in the exome of cancer cells are passengers, which do not affect the reproductive rate of the cell. Passengers can provide important information about the evolutionary history of an individual cancer, and serve as a molecular clock. Passengers can also become targets for immunotherapy or confer resistance to treatment. We study the stochastic expansion of a population of cancer cells describing the growth of primary tumors or metastatic lesions. We first analyze the process by looking forward in time and calculate the fixation probabilities and frequencies of successive passenger mutations ordered by their time of appearance. We compute the likelihood of specific evolutionary trees, thereby informing the phylogenetic reconstruction of cancer evolution in individual patients. Next, we derive results looking backward in time: for a given subclonal mutation we estimate the number of cancer cells that were present at the time when that mutation arose. We derive exact formulas for the expected numbers of subclonal mutations of any frequency. Fitting this formula to cancer sequencing data leads to an estimate for the ratio of birth and death rates of cancer cells during the early stages of clonal expansion. PMID- 26828430 TI - Evaluation of Chlorella as a Decorporation Agent to Enhance the Elimination of Radioactive Strontium from Body. AB - BACKGROUND: Release of radionuclides, such as 137Cs and 90Sr, into the atmosphere and the ocean presents an important problem because internal exposure to 137Cs and 90Sr could be very harmful to humans. Chlorella has been reported to be effective in enhancing the excretion of heavy metals; thus, we hypothesized that Chlorella could also enhance the elimination of 137Cs or 90Sr from the body. We evaluated the potential of Chlorella as a decorporation agent in vitro and in vivo, using 85Sr instead of 90Sr. METHODS: In vitro experiments of adsorption of 137Cs and 85Sr to Chlorella were performed under wide pH conditions. The maximum sorption capacity of Chlorella to strontium was estimated using the Langmuir model. A 85Sr solution was orally administrated to mice pretreated with Chlorella. At 48 h after 85Sr administration, the biodistribution of radioactivity was determined. RESULTS: In the in vitro experiments, although 85Sr barely adsorbed to Chlorella at low pH, the 85Sr adsorption ratio to Chlorella increased with increasing pH. The maximum sorption capacity of Chlorella to strontium was 9.06 mg / g. 137Cs barely adsorbed to Chlorella under any pH conditions. In the biodistribution experiments, bone accumulation of radioactivity after 85Sr administration was significantly decreased in the Chlorella pretreatment group compared with the non-treatment control group. CONCLUSIONS: In conclusion, these results indicated that Chlorella could inhibit the absorption of 90Sr into the blood and enhance the elimination of 90Sr from the body through adsorption in intestine. Further studies are required to elucidate the mechanism and the components of Chlorella needed for adsorption to strontium and could promote the development of more effective decorporation agents. PMID- 26828431 TI - Peptide-Based Optical uPAR Imaging for Surgery: In Vivo Testing of ICG-Glu-Glu AE105. AB - Near infrared intra-operative optical imaging is an emerging technique with clear implications for improved cancer surgery by enabling a more distinct delineation of the tumor margins during resection. This modality has the potential to increase the number of patients having a curative radical tumor resection. In the present study, a new uPAR-targeted fluorescent probe was developed and the in vivo applicability was evaluated in a human xenograft mouse model. Most human carcinomas express high level of uPAR in the tumor-stromal interface of invasive lesions and uPAR is therefore considered an ideal target for intra-operative imaging. Conjugation of the flourophor indocyanine green (ICG) to the uPAR agonist (AE105) provides an optical imaging ligand with sufficiently high receptor affinity to allow for a specific receptor targeting in vivo. For in vivo testing, human glioblastoma xenograft mice were subjected to optical imaging after i.v. injection of ICG-AE105, which provided an optimal contrast in the time window 6-24 h post injection. Specificity of the uPAR-targeting probe ICG-AE105 was demonstrated in vivo by 1) no uptake of unconjugated ICG after 15 hours, 2) inhibition of ICG-AE105 tumor uptake by a bolus injection of the natural uPAR ligand pro-uPA, and finally 3) the histological colocalization of ICG-AE105 fluorescence and immunohistochemical detected human uPAR on resected tumor slides. Taken together, our data supports the potential use of this probe for intra-operative optical guidance in cancer surgery to ensure complete removal of tumors while preserving adjacent, healthy tissue. PMID- 26828432 TI - Doxycycline Protects Thymic Epithelial Cells from Mitomycin C-Mediated Apoptosis In Vitro via Trx2-NF-kappaB-Bcl-2/Bax Axis. AB - BACKGROUND/AIMS: Age-associated and stress-induced involution of the thymus is accompanied by reduced numbers of thymic epithelial cells (TECs) and severe reduction in peripheral T cell repertoire specificities. These events seriously affect immune function, but the mechanisms involved are unclear. Our preliminary findings showed that doxycycline (Dox) could drive the proliferation of a TEC line (MTEC1 cells) partially via the MAPK signaling pathway. Dox can also up regulate IL-6 and GM-CSF expression via the NF-kappaB and MAPK/ERK pathways. Herein, we investigate the effects and mechanisms used by Dox that protect against mitomycin C (MMC)-induced MTEC1 cell apoptosis. METHODS: MTEC1 cells were treated with Dox, MMC, and Dox plus MMC for different amounts of time. The expression of Trx2, NF-kappaB, Bcl-2, and Bax proteins were then detected by western blotting. RESULTS: Our findings show that Dox protects MTEC1 cells from MMC-induced apoptosis. Dox up-regulated the expression of Trx2 and promoted NF kappaB phosphorylation. Meanwhile, Dox also increased the expression of Bcl-2, partially reduced the expression of Bax, and normalized the ratio of Bcl-2 to Bax. CONCLUSION: Dox exerts an anti-apoptosis function via the NF-kappaB-Bcl 2/Bax and Trx2-ASK1/JNK pathways in vitro. Therefore, Dox may represent a drug that could be used to attenuate thymic senescence, rescue thymic function, and promote T cell reconstitution. PMID- 26828433 TI - The Salivary Scavenger and Agglutinin (SALSA) in Healthy and Complicated Pregnancy. AB - Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. The etiology is not clear, but an immune attack towards components of placenta or fetus has been indicated. This involves activation of the complement system in the placenta. We have previously described the presence of the complement-regulating protein salivary scavenger and agglutinin (SALSA) in amniotic fluid. In this study we investigated the potential role of SALSA in pregnancy by analyzing its presence in amniotic fluid and placental tissue during healthy and complicated pregnancies. SALSA levels in amniotic fluid increased during pregnancy. Before 20 weeks of gestation the levels were slightly higher in patients who later developed pre-eclampsia than in gestation age-matched controls. In the placenta of pre-eclamptic patients syncytial damage is often followed by the formation of fibrinoid structures. SALSA was found clustered into these fibrinoid structures in partial co-localization with complement C1q and fibronectin. In vitro analysis showed direct protein binding of SALSA to fibronectin. SALSA binds also to fibrin/fibrinogen but did not interfere with the blood clotting process in vitro. Thus, in addition to antimicrobial defense and epithelial differentiation, the data presented here suggest that SALSA, together with fibronectin and C1q, may be involved in the containment of injured placental structures into fibrinoids. PMID- 26828435 TI - Economic Cost of Campylobacter, Norovirus and Rotavirus Disease in the United Kingdom. AB - OBJECTIVES: To estimate the annual cost to patients, the health service and society of infectious intestinal disease (IID) from Campylobacter, norovirus and rotavirus. DESIGN: Secondary data analysis. SETTING: The United Kingdom population, 2008-9. MAIN OUTCOME MEASURES: Cases and frequency of health services usage due to these three pathogens; associated healthcare costs; direct, out-of pocket expenses; indirect costs to patients and caregivers. RESULTS: The median estimated costs to patients and the health service at 2008-9 prices were: Campylobacter L50 million (95% CI: L33m-L75m), norovirus L81 million (95% CI: L63m-L106m), rotavirus L25m (95% CI: L18m-L35m). The costs per case were approximately L30 for norovirus and rotavirus, and L85 for Campylobacter. This was mostly borne by patients and caregivers through lost income or out-of-pocket expenditure. The cost of Campylobacter-related Guillain-Barre syndrome hospitalisation was L1.26 million (95% CI: L0.4m-L4.2m). CONCLUSIONS: Norovirus causes greater economic burden than Campylobacter and rotavirus combined. Efforts to control IID must prioritise norovirus. For Campylobacter, estimated costs should be considered in the context of expenditure to control this pathogen in agriculture, food production and retail. Our estimates, prior to routine rotavirus immunisation in the UK, provide a baseline vaccine cost-effectiveness analyses. PMID- 26828434 TI - A Small Secreted Virulence-Related Protein Is Essential for the Necrotrophic Interactions of Sclerotinia sclerotiorum with Its Host Plants. AB - Small, secreted proteins have been found to play crucial roles in interactions between biotrophic/hemi-biotrophic pathogens and plants. However, little is known about the roles of these proteins produced by broad host-range necrotrophic phytopathogens during infection. Here, we report that a cysteine-rich, small protein SsSSVP1 in the necrotrophic phytopathogen Sclerotinia sclerotiorum was experimentally confirmed to be a secreted protein, and the secretion of SsSSVP1 from hyphae was followed by internalization and cell-to-cell movement independent of a pathogen in host cells. SsSSVP1?SP could induce significant plant cell death and targeted silencing of SsSSVP1 resulted in a significant reduction in virulence. Through yeast two-hybrid (Y2H), coimmunoprecipitation (co-IP) and bimolecular fluorescence complementation (BiFC) assays, we demonstrated that SsSSVP1?SP interacted with QCR8, a subunit of the cytochrome b-c1 complex of mitochondrial respiratory chain in plants. Double site-directed mutagenesis of two cysteine residues (C38 and C44) in SsSSVP1?SP had significant effects on its homo-dimer formation, SsSSVP1?SP-QCR8 interaction and plant cell death induction, indicating that partial cysteine residues surely play crucial roles in maintaining the structure and function of SsSSVP1. Co-localization and BiFC assays showed that SsSSVP1?SP might hijack QCR8 to cytoplasm before QCR8 targeting into mitochondria, thereby disturbing its subcellular localization in plant cells. Furthermore, virus induced gene silencing (VIGS) of QCR8 in tobacco caused plant abnormal development and cell death, indicating the cell death induced by SsSSVP1?SP might be caused by the SsSSVP1?SP-QCR8 interaction, which had disturbed the QCR8 subcellular localization and hence disabled its biological functions. These results suggest that SsSSVP1 is a potential effector which may manipulate plant energy metabolism to facilitate the infection of S. sclerotiorum. Our findings indicate novel roles of small secreted proteins in the interactions between host-non-specific necrotrophic fungi and plants, and highlight the significance to illuminate the pathogenic mechanisms of this type of interaction. PMID- 26828438 TI - DIMENSIONS OF PERSONALITY: II. SEPARATE FACTOR STRUCTURES IN GUILFORD AND CATTELL TRAIT MARKERS. AB - As fully described in the first paper of this series (Sells, Demaree and Will, 1970), this study involves a series of independent factor analyses and .rotations of 300 Guilford items, provided as markers for 15 Guilford source factons and 300 additional items, provided as markers for 17 Cattell source factors. PMID- 26828439 TI - PERSONALITY STRUCTURE CHECKED IN PRIMARY OBJECTIVE TEST FACTORS, FOR A MIXED NORMAL AND PSYCHOTIC SAMPLE. AB - An experiment was undertaken to determine how far the consistent personality structure previously found separately in noma1 and psychotic populations, in terms of factors measured in objective behaviaral perfomance within the age of a joint normal-psychotic population. One hundred variables embodied in 66 types of subjects were chosen to mark 18 known factors measured on 114 adult (men and women) normals and 228 psychotics. The number of-factors measured by the test was 24. They rotated to a very conspicuous simple structure resolution reaching 82% in the hyperplane. By Burt's congruence test 20 of these matched the factors (the 18 intended, plus 2 others) as known in the homogeneous population. PMID- 26828437 TI - Intrinsic GTP hydrolysis is observed for a switch 1 variant of Cdc42 in the presence of a specific GTPase inhibitor. AB - The Ras-related protein Cell division cycle 42 (Cdc42) is important in cell signaling processes. Protein interactions involving Cdc42 occur primarily in flexible "Switch" regions that help regulate effector binding. We studied the kinetics of intrinsic GTP hydrolysis reaction in the absence and presence of a biologically active peptide derivative of a p21-activated kinase effector (PBD46) for wt Cdc42 and compared it to the Switch 1 variant Cdc42(T35A). While the binding of PBD46 to wt Cdc42 results in complete inhibition of GTP hydrolysis, this interaction in Cdc42(T35A) does not. Comparison of the crystal structure of wt Cdc42 in the absence of effector (1AN0.pdb), as well as the NMR structure of wt Cdc42 bound to an effector in the Switch 1 region (1CF4.pdb) ( www.rcsb.org ) suggests that the orientation of T(35) with bound Mg(2+) changes in the presence of effector, resulting in movement of GTP away from the catalytic box leading to the inhibition of GTP hydrolysis. For Cdc42(T35A), molecular dynamics simulations and structural analyses suggest that the nucleotide does not undergo the conformational shift observed for the wt Cdc42-effector interaction. Our data suggest that change in dynamics in the Switch 1 region of Cdc42 caused by the T35A mutation (Chandrashekar, et al. 2011, Biochemistry, 50, p. 6196) fosters a conformation for this Cdc42 variant that allows hydrolysis of GTP in the presence of PBD46, and that alteration of the conformational dynamics could potentially modulate Ras-related over-activity. PMID- 26828436 TI - Mitochondria in human pluripotent stem cell apoptosis. AB - Human pluripotent stem cells (hPSCs) have great potential in regenerative medicine because they can differentiate into any cell type in the body. Genome integrity is vital for human development and for high fidelity passage of genetic information across generations through the germ line. To ensure genome stability, hPSCs maintain a lower rate of mutation than somatic cells and undergo rapid apoptosis in response to DNA damage and additional cell stresses. Furthermore, cellular metabolism and the cell cycle are also differentially regulated between cells in pluripotent and differentiated states and can aid in protecting hPSCs against DNA damage and damaged cell propagation. Despite these safeguards, clinical use of hPSC derivatives could be compromised by tumorigenic potential and possible malignant transformation from failed to differentiate cells. Since hPSCs and mature cells differentially respond to cell stress, it may be possible to specifically target undifferentiated cells for rapid apoptosis in mixed cell populations to enable safer use of hPSC-differentiated cells in patients. PMID- 26828440 TI - Multivariate Analysis of Dichotomous Variables: A General Method. AB - A method for extimating both additive and interactive effects of several independent dichotomous variables on a dichotomous criterion is proposed and related to explicit causal assumptions. Parameters of the stochastic model are estimated by observed conditional probabilities, a procedure that maximally reduces variance. PMID- 26828441 TI - EVALUATING FACTOR INVARIANCE IN OBLIQUE SPACE: BASELINE DATA GENERATED FROM RANDOM NUMBERS. AB - The invariance of oblique factors under random data conditions is investigated as a function of sample size (50, 100, 200), number of variables (15, 30, 45), and number of extracted factors (5, 10). PMID- 26828442 TI - BRIEF REPORT: THE EQUIVALENCE OF TWO MULTIVARIATE CLASSlFICATION SCHEMES. AB - The equivalence of two multivariate classification schemes is shown when the sizes of the samples drawn from the populations to which assignment is required are identical. One scheme is based on posterior probabilities determined from a Bayesian density function; the second scheme is based on likelihood ratio discriminated scores. Both of these procedures involve prior probabilities; if estimates of these priors are obtained from the identical sample sizes, the equivalence follows. PMID- 26828443 TI - Ensuring Health Plans' Compliance With MHPAEA and the ACA. PMID- 26828450 TI - Optimization of Cultured Human Corneal Endothelial Cell Sheet Transplantation and Post-Operative Sheet Evaluation in a Rabbit Model. AB - PURPOSE: To optimize cultured human corneal endothelial cell (cHCEC) sheet transplantation technique for maintenance of cHCEC viability. MATERIALS AND METHODS: cHCEC sheets cultured on a collagen scaffold were covered with or without Viscoat(r) and exposed to humidified air in the incubator. cHCEC sheets with or without Viscoat(r) were transplanted into cadaveric porcine eyes by the DSAEK technique with full air tamponade and incubated for various time periods. Then cell viability was determined by using the live/dead assay kit. cHCEC sheets with Viscoat(r) were transplanted into rabbit eyes and the sheets were histologically evaluated before and 14 days after transplantation. RESULTS: A collagen scaffold and Viscoat(r) were effective for protecting cHCEC from damage due to air exposure in vitro. All cells died after 18 hours of air exposure in porcine eyes in Viscoat(r) untreated control. In contrast, Viscoat(r) treatment sustained full cell viability following 2 hours and could maintain approximately 80% viability after 18 hours. In a rabbit model, transplanted cHCEC sheet with Viscoat(r) maintained cell density at 2803 +/- 229 mm(2) (18% cell loss) and expression of N-cadherin, zonula occludens-1, and actin-filament localized to cell boundary as similar as donor HCEC. CONCLUSION: Viscoat(r) can contribute to cHCEC protection from damage caused by exposure to air. PMID- 26828451 TI - Complexity of nutritional behavior: Capturing and depicting its interrelated factors in a cause-effect model. AB - The aim of this article is to demonstrate the complexity of nutritional behavior and to increase understanding of this complex phenomenon. We developed a cause effect model based on current literature, expert consultation, and instruments dealing with complexity. It presents factors from all dimensions of nutrition and their direct causal relationships with specification of direction, strength, and type. Including the interplay of all relationships, the model reveals cause effect chains, feedback loops, multicausalities, and side effects. Analyses based on the model can further enhance understanding of nutritional behavior and help identify starting points for measures to modify food consumption. PMID- 26828452 TI - A new hexacyclic triterpene acid from the roots of Euscaphis japonica and its inhibitory activity on triglyceride accumulation. AB - A new taraxerene-type hexacyclic triterpene acid named (12R,13S)-3-methoxy-12,13 cyclo-taraxerene-2,14-diene-1-one-28-oic acid (1), together with a known compound 3,7-dihydroxy-5-octanolide (2), was isolated from the roots of Euscaphis japonica. The structure of new compound 1 was elucidated on the basis of NMR, HR ESIMS and X-ray diffraction analysis. It showed promising inhibitory activity on oleic acid induced triglyceride accumulation on HepG2 cells. PMID- 26828453 TI - Preparation and in vitro/pharmacokinetic/pharmacodynamic evaluation of a slow release nano-liposomal form of prednisolone. AB - A nano-liposomal carrier was prepared for the anti-inflammatory drug prednisolone acetate (PA). The drug showed remarkable loading in the nano-carriers. The drug loaded nano-liposmes with average sizes of about 186 nm and zeta potentials of 20 mV were obtained. Our drug release studies showed an apparently zero-order trend with only 18% of the drug released in the first 120 h. Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) analyses showed no chemical interaction between the drug and carrier. Transmission electron microscopy (TEM) imaging showed near-spherical drug containing nano-carriers. The intramuscular (IM) trial of the nanoformulation compared with the free drug showed both pharmacokinetic (lower Cmax, higher area under the curve (AUC)) and pharmacodynamic (higher and longer lasting anti inflammatory effect, both macroscopically and biochemically) superiority for the nano-liposomal drug above the free prednisolone in rats. PMID- 26828454 TI - Zoledronic acid induces dose-dependent increase of antigen-specific CD8 T-cell responses in combination with peptide/poly-IC vaccine. AB - Zoledronic acid (ZA) is used for treating osteoporosis and for preventing skeletal fractures in cancer patients suffering from myeloma and prostate cancer. It is also reported to directly induce cancer cell apoptosis and indirectly modulate T-cell immune response as an antitumor agent. In this study, the effect of ZA following peptide/polyinosinic-polycytidylic acid (poly-IC) vaccination was investigated in a murine tumor model. The combination of ZA with peptide/poly-IC vaccine showed a synergistic effect on the induction of antigen-specific CD8 T cell response. Three consecutive intravenous administrations of ZA was defined to induce the highest CD8 T-cell response. Further, total splenocyte counts and antigen-specific CD8 T-cell response gradually increased depending on the dose of ZA. In tumor-bearing mice, ZA showed a dose-dependent decrease of growth and prolonged survival. Treatment with ZA only decreased the number of CD11b(+)Gr1(+) myeloid cells in blood. Our results demonstrate that the use of ZA could improve antitumor immune responses induced by the peptide/poly-IC vaccine. PMID- 26828455 TI - Cholera toxin B subunit pentamer reassembled from Escherichia coli inclusion bodies for use in vaccination. AB - The cholera toxin B subunit (CTB) is secreted in its pentameric form from Escherichia coli if its leader peptide is replaced with one of E. coli origin. However, the secretion of the pentamer is generally severely impaired when the molecule is mutated or fused to a foreign peptide. Therefore, we attempted to regenerate pentameric CTB from the inclusion bodies (IBs) of E. coli. Stepwise dialysis of the IBs solubilized in guanidine hydrochloride predominantly generated soluble high-molecular-mass (HMM) aggregates and only a small fraction of pentamer. Three methods to reassemble homogeneous pentameric molecules were evaluated: (i) using a pentameric coiled-coil fusion partner, expecting it to function as an assembly core; (ii) optimizing the protein concentration during refolding; and (iii) eliminating contaminants before refolding. Coiled-coil fusion had some effect, but substantial amounts of HMM aggregates were still generated. Varying the protein concentration from 0.05 mg/mL to 5mg/mL had almost no effect. In contrast, eliminating the contaminants before refolding had a robust effect, and only the pentamer was regenerated, with no detectable HMM aggregates. Surprisingly, the protein concentration at refolding was up to 5mg/mL when the contaminants were removed, with no adverse effects on refolding. The regenerated pentamer was indistinguishable in its biochemical and immunological characteristics from CTB secreted from E. coli or choleragenoid from Vibrio cholerae. This study provides a simple but very efficient strategy for pentamerizing CTB with a highly homogeneous molecular conformation, with which it may be feasible to engineer CTB derivatives and CTB fusion antigens. PMID- 26828456 TI - All Plagiarism Is Not Alike. PMID- 26828457 TI - The Fate of Adjacent Segments After Anterior Cervical Discectomy and Fusion: The Influence of an Anterior Plate System. AB - OBJECTIVE: The purpose of this study was to compare anterior cervical discectomy and fusion with cage alone (ACDF-CA) and anterior cervical discectomy and fusion with cage and plate (ACDF-CP) with regard to adjacent segment degeneration (ASD) diagnosed by the use of CT and MRI with retrospective matched cohort design. METHODS: This study enrolled 68 patients who underwent single-level ACDF who were diagnosed with cervical degenerative disc disease and were followed up for at least 2 years with plain radiographs, computed tomography, and magnetic resonance imaging. The patients were divided into 2 groups according to the operation method: ACDF-CA (33 patients) and ACDF-CP (35 patients). RESULTS: ASD occurred in 4 of 33 patients who underwent ACDF-CA and 9 of 35 patients who underwent ACDF-CP as determined by computed tomography and magnetic resonance imaging. The upper segment range of motion and lower segment range of motion increased in both groups postoperatively. The increase was greater in the ACDF-CP group without statistical significance. The upper segment disc height and lower segment disc height gradually decreased in both groups over time. The decrease was significantly greater in the ACDF-CP group at each follow-up visit. Pseudarthrosis and cage subsidence was observed more in the ACDF-CA group. The pain intensity for the neck in the ACDF-CA group was increased 12 and 24 months postoperatively. CONCLUSIONS: The anterior plate system in ACDF tends to increase adjacent segmental motion and decrease adjacent segmental disc height. In addition, irrespective of clinical symptoms, ACDF-CP has a greater tendency to result in ASD than ACDF-CA after 24 months after surgery. PMID- 26828458 TI - Hypothermia not Supported as a Therapeutic Option for Traumatic Brain Injury in Recent Randomized Trial. PMID- 26828459 TI - No Early Mobilization After Stroke: Lessons Learned from the AVERT Trial. PMID- 26828460 TI - Understanding Neurogenesis in the Subventricular Zone and the Capacity for Transcriptional Modulation in Ischemic Brain Injury. PMID- 26828461 TI - Brain Contusions and SUR1 Receptors: Has a New Target Been Born? PMID- 26828462 TI - The Utility of Ankle-Brachial Index as a Predictor of Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage. AB - OBJECTIVE: Delayed cerebral ischemia (DCI) can cause significant morbidity and mortality in patients suffering from aneurysmal subarachnoid hemorrhage (SAH). Because arterial stiffness has been correlated with vascular risk factors, we evaluated whether the ankle-brachial index (ABI), the ratio of the ankle and brachial systolic blood pressures, can predict DCI. METHODS: In a prospective cohort study, we measured the ABIs of 24 patients with aneurysmal SAH during the weeks after SAH. Angiographic vasospasm was evaluated via diagnostic cerebral angiograms. Transcranial Doppler (TCD) was used to assess associations among ABI, DCI, and angiographic vasospasm. RESULTS: Patients were evaluated on the basis of the presence or absence of DCI (days 3-14 after SAH). Demographic and history factors were similar between the DCI and non-DCI groups. Patients in the DCI group had a greater modified Fisher grade (P = 0.029) and were more likely to have been treated via clipping (P = 0.032) and to demonstrate angiographic vasospasm (P = 0.009). Mean TCD values in the 2 groups were significantly different after day 5 in varied arterial distributions (P < 0.05). ABI values in the DCI group were significantly lower on posthemorrhage days 2-13 and when averaged over the 2-week study period (P < 0.05). An average ABI >1.045 on days 2 7 was 85% sensitive and 82% specific for predicting absence of DCI. CONCLUSIONS: In this small single-center study, lower ABI values were strongly associated with SAH-induced DCI, which may provide a tool for managing DCI in aneurysmal SAH. PMID- 26828463 TI - Sparse Inverse Covariance Estimation with L0 Penalty for Network Construction with Omics Data. AB - Constructing coexpression and association networks with omics data is crucial for studying gene-gene interactions and underlying biological mechanisms. In recent years, learning the structure of a Gaussian graphical model from high-dimensional data using L1 penalty has been well-studied and many applications in bioinformatics and computational biology have been found. However, besides the problem of biased estimators with LASSO, L1 does not always choose the true model consistently. Based on our previous work with L0 regularized regression (Liu and Li, 2014), we propose an L0 regularized sparse inverse covariance estimation (L0RICE) for structure learning with the efficient alternating direction (AD) method. The proposed method is robust and has the oracle property. The proposed method is applied to omics data including data, from next-generation sequencing technologies. Novel procedures for network construction and high-order gene-gene interaction detection with omics data are developed. Results from simulation and real omics data analysis indicate that L0 regularized structure learning can identify high-order correlation structure with lower false positive rate and outperform graphical lasso by a large margin. PMID- 26828464 TI - Spatial analysis of volatile organic compounds in South Philadelphia using passive samplers. AB - Select volatile organic compounds (VOCs) were measured in the vicinity of a petroleum refinery and related operations in South Philadelphia, Pennsylvania, USA, using passive air sampling and laboratory analysis methods. Two-week, time integrated samplers were deployed at 17 sites, which were aggregated into five site groups of varying distances from the refinery. Benzene, toluene, ethylbenzene, and xylene isomers (BTEX) and styrene concentrations were higher near the refinery's fenceline than for groups at the refinery's south edge, mid distance, and farther removed locations. The near fenceline group was significantly higher than the refinery's north edge group for benzene and toluene but not for ethylbenzene or xylene isomers; styrene was lower at the near fenceline group versus the north edge group. For BTEX and styrene, the magnitude of estimated differences generally increased when proceeding through groups ever farther away from the petroleum refining. Perchloroethylene results were not suggestive of an influence from refining. These results suggest that emissions from the refinery complex contribute to higher concentrations of BTEX species and styrene in the vicinity of the plant, with this influence declining as distance from the petroleum refining increases. IMPLICATIONS: Passive sampling methodology for VOCs as discussed here is employed in recently enacted U.S. Environmental Protection Agency Methods 325A/B for determination of benzene concentrations at refinery fenceline locations. Spatial gradients of VOC concentration near the refinery fenceline were discerned in an area containing traffic and other VOC related sources. Though limited, these findings can be useful in application of the method at such facilities to ascertain source influence. PMID- 26828466 TI - Preventive and Therapeutic Effects of Chinese Herbal Compounds against Hepatocellular Carcinoma. AB - Traditional Chinese Medicines, unique biomedical and pharmaceutical resources, have been widely used for hepatocellular carcinoma (HCC) prevention and treatment. Accumulated Chinese herb-derived compounds with significant anti cancer effects against HCC have been identified. Chinese herbal compounds are effective in preventing carcinogenesis, inhibiting cell proliferation, arresting cell cycle, inducing apoptosis, autophagy, cell senescence and anoikis, inhibiting epithelial-mesenchymal transition, metastasis and angiogenesis, regulating immune function, reversing drug resistance and enhancing the effects of chemotherapy in HCC. This paper comprehensively reviews these compounds and their effects on HCC. Finally, the perspectives and rational application of herbal compounds for HCC management are discussed. PMID- 26828465 TI - 3B11-N, a monoclonal antibody against MERS-CoV, reduces lung pathology in rhesus monkeys following intratracheal inoculation of MERS-CoV Jordan-n3/2012. AB - Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was identified in 2012 as the causative agent of a severe, lethal respiratory disease occurring across several countries in the Middle East. To date there have been over 1600 laboratory confirmed cases of MERS-CoV in 26 countries with a case fatality rate of 36%. Given the endemic region, it is possible that MERS-CoV could spread during the annual Hajj pilgrimage, necessitating countermeasure development. In this report, we describe the clinical and radiographic changes of rhesus monkeys following infection with 5*10(6) PFU MERS-CoV Jordan-n3/2012. Two groups of NHPs were treated with either a human anti-MERS monoclonal antibody 3B11-N or E410-N, an anti-HIV antibody. MERS-CoV Jordan-n3/2012 infection resulted in quantifiable changes by computed tomography, but limited other clinical signs of disease. 3B11 N treated subjects developed significantly reduced lung pathology when compared to infected, untreated subjects, indicating that this antibody may be a suitable MERS-CoV treatment. PMID- 26828467 TI - Synthesis, Structure and Cytotoxic Activity of Mono- and Dialkoxy Derivatives of 5,8-Quinolinedione. AB - A series of 5,8-quinolinedione derivatives containing one or two alkoxy groups was synthesized and characterized by 1H- and (13)C-NMR, IR and MS spectra. X-ray diffraction was used to investigate the crystal structures of 6-chloro-7-(2 cyjanoethoxy)-5,8-quinolinedione and 6,7-di(2,2,2-trifloroethoxy)-5,8 quinolinedione. All studied compounds were tested in vitro for their antiproliferative activity against three human cancer cell lines and human normal fibroblasts. Most of the compounds showed higher cytotoxicity than the starting compound, 6,7-dichloro-5,8-quinolinedione, and cisplatin, which was used as a reference agent. PMID- 26828468 TI - Chemoinformatics: Achievements and Challenges, a Personal View. AB - Chemoinformatics provides computer methods for learning from chemical data and for modeling tasks a chemist is facing. The field has evolved in the past 50 years and has substantially shaped how chemical research is performed by providing access to chemical information on a scale unattainable by traditional methods. Many physical, chemical and biological data have been predicted from structural data. For the early phases of drug design, methods have been developed that are used in all major pharmaceutical companies. However, all domains of chemistry can benefit from chemoinformatics methods; many areas that are not yet well developed, but could substantially gain from the use of chemoinformatics methods. The quality of data is of crucial importance for successful results. Computer-assisted structure elucidation and computer-assisted synthesis design have been attempted in the early years of chemoinformatics. Because of the importance of these fields to the chemist, new approaches should be made with better hardware and software techniques. Society's concern about the impact of chemicals on human health and the environment could be met by the development of methods for toxicity prediction and risk assessment. In conjunction with bioinformatics, our understanding of the events in living organisms could be deepened and, thus, novel strategies for curing diseases developed. With so many challenging tasks awaiting solutions, the future is bright for chemoinformatics. PMID- 26828469 TI - Antibacterial Activity and Cytotoxicity of Silver(I) Complexes of Pyridine and (Benz)Imidazole Derivatives. X-ray Crystal Structure of [Ag(2,6 di(CH2OH)py)2]NO3. AB - Selected aspects of the biological activity of a series of six nitrate silver(I) complexes with pyridine and (benz)imidazole derivatives were investigated. The present study evaluated the antibacterial activities of the complexes against three Gram-negative strains: Pseudomonas aeruginosa ATCC 15442, Escherichia coli ATCC 25922 and Proteus hauseri ATCC 13315. The results were compared with those of silver nitrate, a silver sulfadiazine drug and appropriate ligands. The most significant antibacterial properties were exerted by silver(I) complexes containing benzimidazole derivatives. The cytotoxic activity of the complexes was examined against B16 (murine melanoma) and 10T1/2 (murine fibroblasts) cells. All of the tested silver(I) compounds were not toxic to fibroblast cells in concentration inhibited cancer cell (B16) viability by 50%, which ranged between 2.44-28.65 uM. The molecular and crystal structure of silver(I) complex of 2,6 di(hydroxymethyl)pyridine was determined by single-crystal X-ray diffraction analysis. The most important features of the crystal packing and intermolecular non-covalent interactions in the Ag(I) complex were quantified via Hirshfeld surface analysis. PMID- 26828470 TI - Design and Characterization of a Novel p1025 Peptide-Loaded Liquid Crystalline System for the Treatment of Dental Caries. AB - Dental caries, mainly caused by the adhesion of Streptococcus mutans to pellicle coated tooth surfaces, is an important public health problem worldwide. A synthetic peptide (p1025) corresponding to residues 1025-1044 of the adhesin can inhibit this binding. Peptides are particularly susceptible to the biological environment; therefore, a p1025 peptide-loaded liquid crystalline system (LCS) consisting of tea tree oil as the oil phase, polyoxypropylene-(5)-polyoxyethylene (20)-cetyl alcohol as the surfactant, and water or 0.5% polycarbophil polymer dispersions as the aqueous phase was employed as a drug delivery platform. This system exhibited anticaries and bioadhesive properties and provided a protective environment to p1025 at the site of action, thereby modulating its action, prolonging its contact with the teeth, and decreasing the frequency of administration. LCSs were characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), and rheological, texture, and bioadhesive tests. PLM and SAXS revealed the presence of hexagonal liquid crystalline phases and microemulsions. Rheological analyses demonstrated that the addition of polymer dispersions favored characteristics such as shear thinning and thixotropy, hence improving buccal application. Bioadhesion tests showed that polymer dispersions contributed to the adhesion onto the teeth. Taken together, LCS could provide a novel pharmaceutical nanotechnology platform for dental caries treatment. PMID- 26828471 TI - Metabolic Profiling and Antioxidant Assay of Metabolites from Three Radish Cultivars (Raphanus sativus). AB - A total of 13 anthocyanins and 33 metabolites; including organic acids, phenolic acids, amino acids, organic compounds, sugar acids, sugar alcohols, and sugars, were profiled in three radish cultivars by using high-performance liquid chromatography (HPLC) and gas chromatography time-of-flight mass spectrometry (GC TOFMS)-based metabolite profiling. Total phenolics and flavonoids and their in vitro antioxidant activities were assessed. Pelargonidins were found to be the major anthocyanin in the cultivars studied. The cultivar Man Tang Hong showed the highest level of anthocyanins (1.89 +/- 0.07 mg/g), phenolics (0.0664 +/- 0.0033 mg/g) and flavonoids (0.0096 +/- 0.0004 mg/g). Here; the variation of secondary metabolites in the radishes is described, as well as their association with primary metabolites. The low-molecular-weight hydrophilic metabolite profiles were subjected to principal component analysis (PCA), hierarchical clustering analysis (HCA), Pearson's correlation analysis. PCA fully distinguished the three radish cultivars tested. The polar metabolites were strongly correlated between metabolites that participate in the TCA cycle. The chemometrics results revealed that TCA cycle intermediates and free phenolic acids as well as anthocyanins were higher in the cultivar Man Tang Hong than in the others. Furthermore; superoxide radical scavenging activities and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging were investigated to elucidate the antioxidant activity of secondary metabolites in the cultivars. Man Tang Hong showed the highest superoxide radical scavenging activity (68.87%) at 1000 MUg/mL, and DPPH activity (20.78%), followed by Seo Ho and then Hong Feng No. 1. The results demonstrate that GC-TOFMS-based metabolite profiling, integrated with chemometrics, is an applicable method for distinguishing phenotypic variation and determining biochemical reactions connecting primary and secondary metabolism. Therefore; this study might provide information on the relationship between primary and secondary metabolites and a synergistic antioxidant ability derived from the secondary metabolites in the radish cultivars. PMID- 26828472 TI - Correction: Rzepecka-Stojko, A., et al. Polyphenols from Bee Pollen: Structure, Absorption, Metabolism and Biological Activity. Molecules 2015, 20, 21732-21749. PMID- 26828473 TI - Naphthalenones and Depsidones from a Sponge-Derived Strain of the Fungus Corynespora cassiicola. AB - Two new naphthalenones, corynenones A and B (1 and 2), and one new depsidone, corynesidone E (3), together with one known depsidone, corynesidone A (4) and two known diphenyl ethers, corynethers A (5) and B (6), were isolated from the sponge derived fungus Corynespora cassiicola XS-20090I7. Their structures including absolute configurations were determined by spectroscopic data and electronic circular dichroism (ECD) spectra. Compounds 4 and 5 showed cytotoxicity against human promyelocytic leukemia HL-60 and human cervical carcinoma HeLa cell lines. PMID- 26828474 TI - Binding between Saikosaponin C and Human Serum Albumin by Fluorescence Spectroscopy and Molecular Docking. AB - Saikosaponin C (SSC) is one of the major active constituents of dried Radix bupleuri root (Chaihu in Chinese) that has been widely used in China to treat a variety of conditions, such as liver disease, for many centuries. The binding of SSC to human serum albumin (HSA) was explored by fluorescence, circular dichroism (CD), UV-vis spectrophotometry, and molecular docking to understand both the pharmacology and the basis of the clinical use of SSC/Chaihu. SSC produced a concentration-dependent quenching effect on the intrinsic fluorescence of HSA, accompanied by a blue shift in the fluorescence spectra. The Stern-Volmer equation showed that this quenching was dominated by static quenching. The binding constant of SSC with HSA was 3.72 * 103 and 2.99 * 103 L.mol(-1) at 26 degrees C and 36 degrees C, respectively, with a single binding site on each SSC and HSA molecule. Site competitive experiments demonstrated that SSC bound to site I (subdomain IIA) and site II (subdomain IIIA) in HSA. Analysis of thermodynamic parameters indicated that hydrogen bonding and van der Waals forces were mostly responsible for SSC-HSA association. The energy transfer efficiency and binding distance between SSC and HSA was calculated to be 0.23 J and 2.61 nm at 26 degrees C, respectively. Synchronous fluorescence and CD measurements indicated that SSC affected HSA conformation in the SSC-HSA complex. Molecular docking supported the experimental findings in conformational changes, binding sites and binding forces, and revealed binding of SSC at the interface between subdomains IIA-IIB. PMID- 26828475 TI - An Update on the Synthesis of Pyrrolo[1,4]benzodiazepines. AB - Pyrrolo[1,4]benzodiazepines are tricyclic compounds that are considered "privileged structures" since they possess a wide range of biological activities. The first encounter with these molecules was the isolation of anthramycin from cultures of Streptomyces, followed by determination of the X-ray crystal structure of the molecule and a study of its interaction with DNA. This opened up an intensive synthetic and biological study of the pyrrolo[2,1 c][1,4]benzodiazepines that has culminated in the development of the dimer SJG 136, at present in Phase II clinical trials. The synthetic efforts have brought to light some new synthetic methodology, while the contemporary work is focused on building trimeric pyrrolo[2,1-c][1,4]benzodiazepines linked together by various heterocyclic and aliphatic chains. It is the broad spectrum of biological activities of pyrrolo[1,2-a][1,4]benzodiazepines that has maintained the interest of researchers to date whereas several derivatives of the even less studied pyrrolo[1,2-d][1,4]benzodiazepines were found to be potent non-nucleoside HIV-1 reverse transcriptase inhibitors. The present review is an update on the synthesis of pyrrolo[2,1-c][1,4]benzodiazepines since the last major review of 2011, while the overview of the synthesis of the other two tricyclic isomers is comprehensive. PMID- 26828476 TI - Acetaminophen Induced Hepatotoxicity in Wistar Rats--A Proteomic Approach. AB - Understanding the mechanism of chemical toxicity, which is essential for cross species and dose extrapolations, is a major challenge for toxicologists. Standard mechanistic studies in animals for examining the toxic and pathological changes associated with the chemical exposure have often been limited to the single end point or pathways. Toxicoproteomics represents a potential aid to the toxicologist to understand the multiple pathways involved in the mechanism of toxicity and also determine the biomarkers that are possible to predictive the toxicological response. We performed an acute toxicity study in Wistar rats with the prototype liver toxin; the acetaminophen (APAP) effects on protein profiles in the liver and its correlation with the plasma biochemical markers for liver injury were analyzed. Three separate groups--control, nontoxic (150 mg/kg) and toxic dose (1500 mg/kg) of APAP--were studied. The proteins extracted from the liver were separated by 2-DE and analyzed by MALDI-TOF. The differential proteins in the gels were analyzed by BIORAD's PDQuest software and identified by feeding the peptide mass fingerprint data to various public domain programs like Mascot and MS-Fit. The identified proteins in toxicity-induced rats were classified based on their putative protein functions, which are oxidative stress (31%), immunity (14%), neurological related (12%) and transporter proteins (2%), whereas in non-toxic dose-induced rats they were oxidative stress (9%), immunity (6%), neurological (14%) and transporter proteins (9%). It is evident that the percentages of oxidative stress and immunity-related proteins were up-regulated in toxicity-induced rats as compared with nontoxic and control rats. Some of the liver drug metabolizing and detoxifying enzymes were depleted under toxic conditions compared with non-toxic rats. Several other proteins were identified as a first step in developing an in-house rodent liver toxicoproteomics database. PMID- 26828477 TI - Regulation of Candida albicans Interaction with Macrophages through the Activation of HOG Pathway by Genistein. AB - The severity of infections caused by Candida albicans, the most common opportunistic human fungal pathogen, needs rapid and effective antifungal treatments. One of the effective ways is to control the virulence factors of the pathogen. Therefore, the current study examined the effects of genistein, a natural isoflavone present in soybeans, on C. albicans. The genistein-treated C. albicans cells were then exposed to macrophages. Although no inhibition effect on the growth rates of C. albicans was noted an enhancement of the immune response to macrophages has been observed, indicated by phagocytosis and release of cytokines TNF-alpha and IL-10. The effect of genistein on the enhanced phagocytosis can be mimicked by the fungicides fludioxonil or iprodione, which inhibit the histidine kinase Cos1p and lead to activation of HOG pathway. The western blot results showed a clear phosphorylation of Hog1p in the wild type strain of C. albicans after incubation with genistein. In addition, effects of genistein on the phosphorylation of Hog1p in the histidine kinase mutants Deltacos1 and Deltasln1 were also observed. Our results thus indicate a new bio activity of genistein on C. albicans by activation of the HOG pathway of the human pathogen C. albicans. PMID- 26828478 TI - Genome-Wide Identification, Characterization and Expression Analysis of the Chalcone Synthase Family in Maize. AB - Members of the chalcone synthase (CHS) family participate in the synthesis of a series of secondary metabolites in plants, fungi and bacteria. The metabolites play important roles in protecting land plants against various environmental stresses during the evolutionary process. Our research was conducted on comprehensive investigation of CHS genes in maize (Zea mays L.), including their phylogenetic relationships, gene structures, chromosomal locations and expression analysis. Fourteen CHS genes (ZmCHS01-14) were identified in the genome of maize, representing one of the largest numbers of CHS family members identified in one organism to date. The gene family was classified into four major classes (classes I-IV) based on their phylogenetic relationships. Most of them contained two exons and one intron. The 14 genes were unevenly located on six chromosomes. Two segmental duplication events were identified, which might contribute to the expansion of the maize CHS gene family to some extent. In addition, quantitative real-time PCR and microarray data analyses suggested that ZmCHS genes exhibited various expression patterns, indicating functional diversification of the ZmCHS genes. Our results will contribute to future studies of the complexity of the CHS gene family in maize and provide valuable information for the systematic analysis of the functions of the CHS gene family. PMID- 26828479 TI - A Common Variant of PROK1 (V67I) Acts as a Genetic Modifier in Early Human Pregnancy through Down-Regulation of Gene Expression. AB - PROK1-V67I has been shown to play a role as a modifier gene in the PROK1-PROKR system of human early pregnancy. To explore the related modifier mechanism of PROK1-V67I, we carried out a comparison study at the gene expression level and the cell function alternation of V67I, and its wild-type (WT), in transiently transfected cells. We, respectively, performed quantitative RT-PCR and ELISA assays to evaluate the protein and/or transcript level of V67I and WT in HTR-8/SV neo, JAR, Ishikawa, and HEK293 cells. Transiently V67I- or WT-transfected HTR 8/SV neo and HEK293 cells were used to investigate cell function alternations. The transcript and protein expressions were down-regulated in all cell lines, ranging from 20% to 70%, compared with WT. There were no significant differences in the ligand activities of V67I and WT with regard to cell proliferation, cell invasion, calcium influx, and tubal formation. Both PROK1 alleles promoted cell invasion and intracellular calcium mobilization, whereas they had no significant effects on cell proliferation and tubal formation. In conclusion, the biological effects of PROK1-V67I on cell functions are similar to those of WT, and the common variant of V67I may act as a modifier in the PROK1-PROKR system through down-regulation of PROK1 expression. This study may provide a general mechanism that the common variant of V67I, modifying the disease severity of PROK1-related pathophysiologies. PMID- 26828480 TI - The Metabolic Fate of ortho-Quinones Derived from Catecholamine Metabolites. AB - ortho-Quinones are produced in vivo through the oxidation of catecholic substrates by enzymes such as tyrosinase or by transition metal ions. Neuromelanin, a dark pigment present in the substantia nigra and locus coeruleus of the brain, is produced from dopamine (DA) and norepinephrine (NE) via an interaction with cysteine, but it also incorporates their alcoholic and acidic metabolites. In this study we examined the metabolic fate of ortho-quinones derived from the catecholamine metabolites, 3,4-dihydroxyphenylethanol (DOPE), 3,4-dihydroxyphenylethylene glycol (DOPEG), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylmandelic acid (DOMA). The oxidation of catecholic substrates by mushroom tyrosinase was followed by UV-visible spectrophotometry. HPLC analysis after reduction with NaBH4 or ascorbic acid enabled measurement of the half-lives of ortho-quinones and the identification of their reaction products. Spectrophotometric examination showed that the ortho-quinones initially formed underwent extensive degradation at pH 6.8. HPLC analysis showed that DOPE quinone and DOPEG-quinone degraded with half-lives of 15 and 30 min at pH 6.8, respectively, and >100 min at pH 5.3. The major product from DOPE-quinone was DOPEG which was produced through the addition of a water molecule to the quinone methide intermediate. DOPEG-quinone yielded a ketone, 2-oxo-DOPE, through the quinone methide intermediate. DOPAC-quinone and DOMA-quinone degraded immediately with decarboxylation of the ortho-quinone intermediates to form 3,4 dihydroxybenzylalcohol (DHBAlc) and 3,4-dihydroxybenzaldehyde (DHBAld), respectively. DHBAlc-quinone was converted to DHBAld with a half-life of 9 min, while DHBAld-quinone degraded rapidly with a half-life of 3 min. This study confirmed the fact that ortho-quinones from DOPE, DOPEG, DOPAC and DOMA are converted to quinone methide tautomers as common intermediates, through proton rearrangement or decarboxylation. The unstable quinone methides afford stable alcoholic or carbonyl products. PMID- 26828481 TI - The Protective Effect of Icariin on Mitochondrial Transport and Distribution in Primary Hippocampal Neurons from 3* Tg-AD Mice. AB - Icariin, a pharmacologically active component isolated from the Chinese herb Epimedium, has been shown to improve spatial learning and memory abilities in Alzheimer's disease (AD) rats through inhibition of Abeta production and tau protein hyperphosphorylation. However, the potential mechanism of icariin-induced protective effects against mitochondrial dysfunctions in AD still remains unclear. In the present study, we investigated the effect of icariin on the modulation of mitochondrial transport and distribution in primary hippocampal cultures from triple-transgenic (3* Tg) AD mice. The results showed that icariin enhanced mitochondrial motility and increased mitochondrial index and mitochondrial length and size in the diseased neurons. Additionally, the expression of the key mitochondrial enzyme, pyruvate dehydrogenase-E1alpha (PDHE1alpha), and the post synaptic density protein 95 (PSD95), was preserved in AD neurons after icariin treatment, accompanied by a downregulation of Abeta and phosphorylated tau expression in the corresponding areas. Further study showed that icariin treatment resulted in a decrease in mitochondrial fission protein dynamin-related protein 1 (Drp1) and an increase in fusion protein Mitofusin 2 (Mfn2). These data indicate that icariin can promote mitochondrial transport, protect mitochondria against fragmentation and preserve the expression of mitochondrial and synaptic functional proteins in AD neurons. Thus, icariin may be a potential therapeutic complement for AD and other mitochondrial malfunction related neuronal degenerative diseases. PMID- 26828483 TI - Usefulness of Intratracheal Instillation Studies for Estimating Nanoparticle Induced Pulmonary Toxicity. AB - Inhalation studies are the gold standard for the estimation of the harmful effects of respirable chemical substances, while there is limited evidence of the harmful effects of chemical substances by intratracheal instillation. We reviewed the effectiveness of intratracheal instillation studies for estimating the hazards of nanoparticles, mainly using papers in which both inhalation and intratracheal instillation studies were performed using the same nanoparticles. Compared to inhalation studies, there is a tendency in intratracheal instillation studies that pulmonary inflammation lasted longer in the lungs. A difference in pulmonary inflammation between high and low toxicity nanoparticles was observed in the intratracheal instillation studies, as in the inhalation studies. Among the endpoints of pulmonary toxicity, the kinetics of neutrophil counts, percentage of neutrophils, and chemokines for neutrophils and macrophages, heme oxygenase-1 (HO-1) in bronchoalveolar lavage fluid (BALF), reflected pulmonary inflammation, suggesting that these markers may be considered the predictive markers of pulmonary toxicity in both types of study. When comparing pulmonary inflammation between intratracheal instillation and inhalation studies under the same initial lung burden, there is a tendency that the inflammatory response following the intratracheal instillation of nanoparticles is greater than or equal to that following the inhalation of nanoparticles. If the difference in clearance in both studies is not large, the estimations of pulmonary toxicity are close. We suggest that intratracheal instillation studies can be useful for ranking the hazard of nanoparticles through pulmonary inflammation. PMID- 26828484 TI - Lingual Epithelial Stem Cells and Organoid Culture of Them. AB - As tongue cancer is one of the major malignant cancers in the world, understanding the mechanism of maintenance of lingual epithelial tissue, which is known to be the origin of tongue cancer, is unquestionably important. However, the actual stem cells that are responsible for the long-term maintenance of the lingual epithelium have not been identified. Moreover, a simple and convenient culture method for lingual epithelial stem cells has not yet been established. Recently, we have shown that Bmi1-positive cells, residing at the second or third layer of the epithelial cell layer at the base of the interpapillary pit (IPP), were slow-cycling and could supply keratinized epithelial cells for over one year, indicating that Bmi1-positive cells are long-term lingual epithelial stem cells. In addition, we have developed a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Here, we discuss current progress in the identification of lingual stem cells and future applications of the lingual culture system for studying the regulatory mechanisms of the lingual epithelium and for regenerative medicine. PMID- 26828482 TI - Aquaporins in Salivary Glands: From Basic Research to Clinical Applications. AB - Salivary glands are involved in saliva secretion that ensures proper oral health. Aquaporins are expressed in salivary glands and play a major role in saliva secretion. This review will provide an overview of the salivary gland morphology and physiology of saliva secretion, and focus on the expression, subcellular localization and role of aquaporins under physiological and pathophysiological conditions, as well as clinical applications involving aquaporins. This review is highlighting expression and localization of aquaporins in human, rat and mouse, the most studied species and is pointing out possible difference between major salivary glands, i.e., parotid, submandibular and sublingual glands. PMID- 26828485 TI - Icaritin Inhibits Collagen Degradation-Related Factors and Facilitates Collagen Accumulation in Atherosclerotic Lesions: A Potential Action for Plaque Stabilization. AB - Most acute coronary syndromes result from rupture of vulnerable atherosclerotic plaques. The collagen content of plaques may critically affect plaque stability. This study tested whether Icaritin (ICT), an intestinal metabolite of Epimedium derived flavonoids, could alter the collagen synthesis/degradation balance in atherosclerotic lesions. Rabbits were fed with an atherogenic diet for four months. Oral administration of ICT (10 mg.kg(-1).day(-1)) was started after two months of an atherogenic diet and lasted for two months. The collagen degradation related parameters, including macrophages accumulation, content and activity of interstitial collagenase-1 (MMP-1), and the collagen synthesis-related parameters, including amount and distribution of smooth muscle cells (SMC) and collagen mRNA/protein levels, were evaluated in the aorta. ICT reduced plasma lipid levels, inhibited macrophage accumulation, lowered MMP-1 mRNA and protein expression, and suppressed proteolytic activity of pro-MMP-1 and MMP-1 in the aorta. ICT changed the distribution of the SMCs towards the fibrous cap of lesions without increasing the amount of SMCs. Higher collagen protein content in lesions and aorta homogenates was observed with ICT treatment compared with the atherogenic diet only, without altered collagen mRNA level. These results suggest that ICT could inhibit the collagen degradation-related factors and facilitate collagen accumulation in atherosclerotic lesions, indicating a new potential of ICT in atherosclerotic plaques. PMID- 26828487 TI - Body-Based Gender Recognition Using Images from Visible and Thermal Cameras. AB - Gender information has many useful applications in computer vision systems, such as surveillance systems, counting the number of males and females in a shopping mall, accessing control systems in restricted areas, or any human-computer interaction system. In most previous studies, researchers attempted to recognize gender by using visible light images of the human face or body. However, shadow, illumination, and time of day greatly affect the performance of these methods. To overcome this problem, we propose a new gender recognition method based on the combination of visible light and thermal camera images of the human body. Experimental results, through various kinds of feature extraction and fusion methods, show that our approach is efficient for gender recognition through a comparison of recognition rates with conventional systems. PMID- 26828486 TI - Mitotic Diversity in Homeostatic Human Interfollicular Epidermis. AB - Despite decades of skin research, regulation of proliferation and homeostasis in human epidermis is still insufficiently understood. To address the role of mitoses in tissue regulation, we utilized human long-term skin equivalents and systematically assessed mitoses during early epidermal development and long-term epidermal regeneration. We now demonstrate four different orientations: (1) horizontal, i.e., parallel to the basement membrane (BM) and suggestive of symmetric divisions; (2) oblique with an angle of 45 degrees -70 degrees ; or (3) perpendicular, suggestive of asymmetric division. In addition, we demonstrate a fourth substantial fraction of suprabasal mitoses, many of which are committed to differentiation (Keratin K10-positive). As verified also for normal human skin, this spatial mitotic organization is part of the regulatory program of human epidermal tissue homeostasis. As a potential marker for asymmetric division, we investigated for Numb and found that it was evenly spread in almost all undifferentiated keratinocytes, but indeed asymmetrically distributed in some mitoses and particularly frequent under differentiation-repressing low-calcium conditions. Numb deletion (stable knockdown by CRISPR/Cas9), however, did not affect proliferation, neither in a three-day follow up study by life cell imaging nor during a 14-day culture period, suggesting that Numb is not essential for the general control of keratinocyte division. PMID- 26828488 TI - A New Void Fraction Measurement Method for Gas-Liquid Two-Phase Flow in Small Channels. AB - Based on a laser diode, a 12 * 6 photodiode array sensor, and machine learning techniques, a new void fraction measurement method for gas-liquid two-phase flow in small channels is proposed. To overcome the influence of flow pattern on the void fraction measurement, the flow pattern of the two-phase flow is firstly identified by Fisher Discriminant Analysis (FDA). Then, according to the identification result, a relevant void fraction measurement model which is developed by Support Vector Machine (SVM) is selected to implement the void fraction measurement. A void fraction measurement system for the two-phase flow is developed and experiments are carried out in four different small channels. Four typical flow patterns (including bubble flow, slug flow, stratified flow and annular flow) are investigated. The experimental results show that the development of the measurement system is successful. The proposed void fraction measurement method is effective and the void fraction measurement accuracy is satisfactory. Compared with the conventional laser measurement systems using standard laser sources, the developed measurement system has the advantages of low cost and simple structure. Compared with the conventional void fraction measurement methods, the proposed method overcomes the influence of flow pattern on the void fraction measurement. This work also provides a good example of using low-cost laser diode as a competent replacement of the expensive standard laser source and hence implementing the parameter measurement of gas-liquid two-phase flow. The research results can be a useful reference for other researchers' works. PMID- 26828489 TI - A Survey on Urban Traffic Management System Using Wireless Sensor Networks. AB - Nowadays, the number of vehicles has increased exponentially, but the bedrock capacities of roads and transportation systems have not developed in an equivalent way to efficiently cope with the number of vehicles traveling on them. Due to this, road jamming and traffic correlated pollution have increased with the associated adverse societal and financial effect on different markets worldwide. A static control system may block emergency vehicles due to traffic jams. Wireless Sensor networks (WSNs) have gained increasing attention in traffic detection and avoiding road congestion. WSNs are very trendy due to their faster transfer of information, easy installation, less maintenance, compactness and for being less expensive compared to other network options. There has been significant research on Traffic Management Systems using WSNs to avoid congestion, ensure priority for emergency vehicles and cut the Average Waiting Time (AWT) of vehicles at intersections. In recent decades, researchers have started to monitor real-time traffic using WSNs, RFIDs, ZigBee, VANETs, Bluetooth devices, cameras and infrared signals. This paper presents a survey of current urban traffic management schemes for priority-based signalling, and reducing congestion and the AWT of vehicles. The main objective of this survey is to provide a taxonomy of different traffic management schemes used for avoiding congestion. Existing urban traffic management schemes for the avoidance of congestion and providing priority to emergency vehicles are considered and set the foundation for further research. PMID- 26828490 TI - A Full Parallel Event Driven Readout Technique for Area Array SPAD FLIM Image Sensors. AB - This paper presents a full parallel event driven readout method which is implemented in an area array single-photon avalanche diode (SPAD) image sensor for high-speed fluorescence lifetime imaging microscopy (FLIM). The sensor only records and reads out effective time and position information by adopting full parallel event driven readout method, aiming at reducing the amount of data. The image sensor includes four 8 * 8 pixel arrays. In each array, four time-to digital converters (TDCs) are used to quantize the time of photons' arrival, and two address record modules are used to record the column and row information. In this work, Monte Carlo simulations were performed in Matlab in terms of the pile up effect induced by the readout method. The sensor's resolution is 16 * 16. The time resolution of TDCs is 97.6 ps and the quantization range is 100 ns. The readout frame rate is 10 Mfps, and the maximum imaging frame rate is 100 fps. The chip's output bandwidth is 720 MHz with an average power of 15 mW. The lifetime resolvability range is 5-20 ns, and the average error of estimated fluorescence lifetimes is below 1% by employing CMM to estimate lifetimes. PMID- 26828492 TI - Improving IMES Localization Accuracy by Integrating Dead Reckoning Information. AB - Indoor positioning remains an open problem, because it is difficult to achieve satisfactory accuracy within an indoor environment using current radio-based localization technology. In this study, we investigate the use of Indoor Messaging System (IMES) radio for high-accuracy indoor positioning. A hybrid positioning method combining IMES radio strength information and pedestrian dead reckoning information is proposed in order to improve IMES localization accuracy. For understanding the carrier noise ratio versus distance relation for IMES radio, the signal propagation of IMES radio is modeled and identified. Then, trilateration and extended Kalman filtering methods using the radio propagation model are developed for position estimation. These methods are evaluated through robot localization and pedestrian localization experiments. The experimental results show that the proposed hybrid positioning method achieved average estimation errors of 217 and 1846 mm in robot localization and pedestrian localization, respectively. In addition, in order to examine the reason for the positioning accuracy of pedestrian localization being much lower than that of robot localization, the influence of the human body on the radio propagation is experimentally evaluated. The result suggests that the influence of the human body can be modeled. PMID- 26828491 TI - Impact of Humidity on Quartz-Enhanced Photoacoustic Spectroscopy Based CO Detection Using a Near-IR Telecommunication Diode Laser. AB - A near-IR CO trace gas sensor based on quartz-enhanced photoacoustic spectroscopy (QEPAS) is evaluated using humidified nitrogen samples. Relaxation processes in the CO-N2-H2O system are investigated. A simple kinetic model is used to predict the sensor performance at different gas pressures. The results show that CO has a ~3 and ~5 times slower relaxation time constant than CH4 and HCN, respectively, under dry conditions. However, with the presence of water, its relaxation time constant can be improved by three orders of magnitude. The experimentally determined normalized detection sensitivity for CO in humid gas is 1.556 * 10(-8) W ? cm (-1)/Hz(1/2). PMID- 26828493 TI - New C4D Sensor with a Simulated Inductor. AB - A new capacitively coupled contactless conductivity detection (C(4)D) sensor with an improved simulated inductor is developed in this work. The improved simulated inductor is designed on the basis of the Riordan-type floating simulated inductor. With the improved simulated inductor, the negative influence of the coupling capacitances is overcome and the conductivity measurement is implemented by the series resonance principle. The conductivity measurement experiments are carried out in three pipes with different inner diameters of 3.0 mm, 4.6 mm and 6.4 mm, respectively. The experimental results show that the designs of the new C(4)D sensor and the improved simulated inductor are successful. The maximum relative error of the conductivity measurement is less than 5%. Compared with the C(4)D sensors using practical inductors, the measurement accuracy of the new C(4)D sensor is comparable. The research results also indicate that the adjustability of a simulated inductor can reduce the requirement for the AC source and guarantee the interchangeableness. Meanwhile, it is recommended that making the potential of one terminal of a simulated inductor stable is beneficial to the running stability. Furthermore, this work indirectly verifies the possibility and feasibility of the miniaturization of the C(4)D sensor by using the simulated inductor technique and lays a good foundation for future research work. PMID- 26828494 TI - Performance Evaluation of the New Compound-Carrier-Modulated Signal for Future Navigation Signals. AB - Navigation Signal based on Compound Carrier (NSCC), is proposed as the potential future global navigation satellite system (GNSS) signal modulation scheme. NSCC, a kind of multi-carrier (MC) signal, is generated by superposition and multi parameter adjustment of sub-carriers. Therefore, a judious choice of parameter configation is needed. The main objective of this paper is to investigate the performance of the NSCC which is influenced by these parameters and to demonstrate its structure characteristics and superiority, employing a comprehensive evaluation system. The results show that the proposed NSCC signal processes full spectral efficiency and limited out of band (OOB) emissions, satisfying the demands of crowed frequency resources. It also presents better performance in terms of spectral separation coefficients (SSCs), tracking accuracy, multipath mitigation capability and anti-jamming reduction compared with the legacy navigation signals. NSCC modulation represents a serious candidate for navigation satellite augmentation systems, especially for signals applied in challenging environments. PMID- 26828495 TI - DeepSurveyCam--A Deep Ocean Optical Mapping System. AB - Underwater photogrammetry and in particular systematic visual surveys of the deep sea are by far less developed than similar techniques on land or in space. The main challenges are the rough conditions with extremely high pressure, the accessibility of target areas (container and ship deployment of robust sensors, then diving for hours to the ocean floor), and the limitations of localization technologies (no GPS). The absence of natural light complicates energy budget considerations for deep diving flash-equipped drones. Refraction effects influence geometric image formation considerations with respect to field of view and focus, while attenuation and scattering degrade the radiometric image quality and limit the effective visibility. As an improvement on the stated issues, we present an AUV-based optical system intended for autonomous visual mapping of large areas of the seafloor (square kilometers) in up to 6000 m water depth. We compare it to existing systems and discuss tradeoffs such as resolution vs. mapped area and show results from a recent deployment with 90,000 mapped square meters of deep ocean floor. PMID- 26828496 TI - An Imaging Sensor-Aided Vision Navigation Approach that Uses a Geo-Referenced Image Database. AB - In determining position and attitude, vision navigation via real-time image processing of data collected from imaging sensors is advanced without a high performance global positioning system (GPS) and an inertial measurement unit (IMU). Vision navigation is widely used in indoor navigation, far space navigation, and multiple sensor-integrated mobile mapping. This paper proposes a novel vision navigation approach aided by imaging sensors and that uses a high accuracy geo-referenced image database (GRID) for high-precision navigation of multiple sensor platforms in environments with poor GPS. First, the framework of GRID-aided vision navigation is developed with sequence images from land-based mobile mapping systems that integrate multiple sensors. Second, a highly efficient GRID storage management model is established based on the linear index of a road segment for fast image searches and retrieval. Third, a robust image matching algorithm is presented to search and match a real-time image with the GRID. Subsequently, the image matched with the real-time scene is considered to calculate the 3D navigation parameter of multiple sensor platforms. Experimental results show that the proposed approach retrieves images efficiently and has navigation accuracies of 1.2 m in a plane and 1.8 m in height under GPS loss in 5 min and within 1500 m. PMID- 26828497 TI - An Online Continuous Human Action Recognition Algorithm Based on the Kinect Sensor. AB - Continuous human action recognition (CHAR) is more practical in human-robot interactions. In this paper, an online CHAR algorithm is proposed based on skeletal data extracted from RGB-D images captured by Kinect sensors. Each human action is modeled by a sequence of key poses and atomic motions in a particular order. In order to extract key poses and atomic motions, feature sequences are divided into pose feature segments and motion feature segments, by use of the online segmentation method based on potential differences of features. Likelihood probabilities that each feature segment can be labeled as the extracted key poses or atomic motions, are computed in the online model matching process. An online classification method with variable-length maximal entropy Markov model (MEMM) is performed based on the likelihood probabilities, for recognizing continuous human actions. The variable-length MEMM method ensures the effectiveness and efficiency of the proposed CHAR method. Compared with the published CHAR methods, the proposed algorithm does not need to detect the start and end points of each human action in advance. The experimental results on public datasets show that the proposed algorithm is effective and highly-efficient for recognizing continuous human actions. PMID- 26828498 TI - A Novel RFID-Based Sensing Method for Low-Cost Bolt Loosening Monitoring. AB - In coal mines, bolt loosening in the cage guide is affected by the harsh environmental factors and cage hoist vibration, leading to significant threats to work safety. It is crucial, to this effect, to successfully detect the status of multipoint bolts of guide structures. This paper proposes a system to monitor bolt status in harsh environments established based on the RFID technique. A proof-of-concept model was demonstrated consisting of a bolt gearing system, passive UHF RFID tags, a reader, and monitoring software. A tinfoil metal film is fixed on the retaining plate and an RFID tag bonded to a large gear, with the bolt to be detected fixed in the center of a smaller gear. The radio-frequency signal cannot be received by the reader if the tag is completely obscured by the tinfoil, and if the bolt is loose, the tag's antenna is exposed when the gear revolves. A radio-frequency signal that carries corresponding bolt's information is transmitted by the RFID tag to the RFID reader due to coil coupling, identifying loose bolt location and reporting them in the software. Confirmatory test results revealed that the system indeed successfully detects bolt loosening and comparative test results (based on a reed switch multipoint bolt loosening monitor system) provided valuable information regarding the strengths and weaknesses of the proposed system. PMID- 26828499 TI - Multi-Target Joint Detection and Estimation Error Bound for the Sensor with Clutter and Missed Detection. AB - The error bound is a typical measure of the limiting performance of all filters for the given sensor measurement setting. This is of practical importance in guiding the design and management of sensors to improve target tracking performance. Within the random finite set (RFS) framework, an error bound for joint detection and estimation (JDE) of multiple targets using a single sensor with clutter and missed detection is developed by using multi-Bernoulli or Poisson approximation to multi-target Bayes recursion. Here, JDE refers to jointly estimating the number and states of targets from a sequence of sensor measurements. In order to obtain the results of this paper, all detectors and estimators are restricted to maximum a posteriori (MAP) detectors and unbiased estimators, and the second-order optimal sub-pattern assignment (OSPA) distance is used to measure the error metric between the true and estimated state sets. The simulation results show that clutter density and detection probability have significant impact on the error bound, and the effectiveness of the proposed bound is verified by indicating the performance limitations of the single-sensor probability hypothesis density (PHD) and cardinalized PHD (CPHD) filters for various clutter densities and detection probabilities. PMID- 26828500 TI - The Study of Cross-layer Optimization for Wireless Rechargeable Sensor Networks Implemented in Coal Mines. AB - Wireless sensor networks deployed in coal mines could help companies provide workers working in coal mines with more qualified working conditions. With the underground information collected by sensor nodes at hand, the underground working conditions could be evaluated more precisely. However, sensor nodes may tend to malfunction due to their limited energy supply. In this paper, we study the cross-layer optimization problem for wireless rechargeable sensor networks implemented in coal mines, of which the energy could be replenished through the newly-brewed wireless energy transfer technique. The main results of this article are two-fold: firstly, we obtain the optimal relay nodes' placement according to the minimum overall energy consumption criterion through the Lagrange dual problem and KKT conditions; secondly, the optimal strategies for recharging locomotives and wireless sensor networks are acquired by solving a cross-layer optimization problem. The cyclic nature of these strategies is also manifested through simulations in this paper. PMID- 26828501 TI - Emergent Sources of Prebiotics: Seaweeds and Microalgae. AB - In recent years, scientists have become aware that human microbiota, in general, and gut microbiota, in particular, play a major role in human health and diseases, such as obesity and diabetes, among others. A large number of evidence has come to light regarding the beneficial effects, either for the host or the gut microbiota, of some foods and food ingredients or biochemical compounds. Among these, the most promising seem to be polysaccharides (PS) or their derivatives, and they include the dietary fibers. Some of these PS can be found in seaweeds and microalgae, some being soluble fibers, such as alginates, fucoidans, carrageenans and exopolysaccharides, that are not fermented, at least not completely, by colonic microbiota. This review gives an overview of the importance of the dietary fibers, as well as the benefits of prebiotics, to human health. The potential of the PS from marine macro- and microalgae to act as prebiotics is discussed, and the different techniques to obtain oligosaccharides from PS are presented. The mechanisms of the benefits of fiber, in general, and the types and benefits of algal fibers in human health are highlighted. The findings of some recent studies that present the potential effects of prebiotics on animal models of algal biomass and their extracts, as well as oligo- and polysaccharides, are presented. In the future, the possibility of using prebiotics to modulate the microbiome, and, consequently, prevent certain human diseases is foreseen. PMID- 26828502 TI - Yessotoxin, a Promising Therapeutic Tool. AB - Yessotoxin (YTX) is a polyether compound produced by dinoflagellates and accumulated in filter feeding shellfish. No records about human intoxications induced by this compound have been published, however it is considered a toxin. Modifications in second messenger levels, protein levels, immune cells, cytoskeleton or activation of different cellular death types have been published as consequence of YTX exposure. This review summarizes the main intracellular pathways modulated by YTX and their pharmacological and therapeutic implications. PMID- 26828503 TI - Patterns of Bacillary Dysentery in China, 2005-2010. AB - Although the incidence of bacillary dysentery in China has been declining progressively, a considerable disease burden still exists. Few studies have analyzed bacillary dysentery across China and knowledge gaps still exist in the aspects of geographic distribution and ecological drivers, seasonality and its association with meteorological factors, urban-rural disparity, prevalence and distribution of Shigella species. Here, we performed nationwide analyses to fill the above gaps. Geographically, we found that incidence increased along an east west gradient which was inversely related to the economic conditions of China. Two large endemically high-risk regions in western China and their ecological drivers were identified for the first time. We characterized seasonality of bacillary dysentery incidence and assessed its association with meteorological factors, and saw that it exhibits north-south differences in peak duration, relative amplitude and key meteorological factors. Urban and rural incidences among China's cities were compared, and disparity associated with urbanization level was invariant in most cities. Balanced decrease of urban and rural incidence was observed for all provinces except Hunan. S. flexneri and S. sonnei were identified as major causative species. Increasing prevalence of S. sonnei and geographic distribution of Shigella species were associated with economic status. Findings and inferences from this study draw broader pictures of bacillary dysentery in mainland China and could provide useful information for better interventions and public health planning. PMID- 26828504 TI - The Cumulative Effect of Gene-Gene and Gene-Environment Interactions on the Risk of Prostate Cancer in Chinese Men. AB - Prostate cancer (PCa) is a multifactorial disease involving complex genetic and environmental factors interactions. Gene-gene and gene-environment interactions associated with PCa in Chinese men are less studied. We explored the association between 36 SNPs and PCa in 574 subjects from northern China. Body mass index (BMI), smoking, and alcohol consumption were determined through self-administered questionnaires in 134 PCa patients. Then gene-gene and gene-environment interactions among the PCa-associated SNPs were analyzed using the generalized multifactor dimensionality reduction (GMDR) and logistic regression methods. Allelic and genotypic association analyses showed that six variants were associated with PCa and the cumulative effect suggested men who carried any combination of 1, 2, or >=3 risk genotypes had a gradually increased PCa risk (odds ratios (ORs) = 1.79-4.41). GMDR analysis identified the best gene-gene interaction model with scores of 10 for both the cross-validation consistency and sign tests. For gene-environment interactions, rs6983561 CC and rs16901966 GG in individuals with a BMI >= 28 had ORs of 7.66 (p = 0.032) and 5.33 (p = 0.046), respectively. rs7679673 CC + CA and rs12653946 TT in individuals that smoked had ORs of 2.77 (p = 0.007) and 3.11 (p = 0.024), respectively. rs7679673 CC in individuals that consumed alcohol had an OR of 4.37 (p = 0.041). These results suggest that polymorphisms, either individually or by interacting with other genes or environmental factors, contribute to an increased risk of PCa. PMID- 26828505 TI - User Perspectives of Characteristics of Improved Cookstoves from a Field Evaluation in Western Kenya. AB - Over half of the world's population uses biomass fuels; these households cook on open fires indoors, increasing their risk of adverse health effects due to household air pollution (HAP) from biomass combustion. This study evaluated six improved cookstoves (ICS) for effectiveness and acceptability in a rural community in Western Kenya. This paper describes women's views on each ICS compared to the traditional three-stone fire. Views on stove characteristics, fuel consumption, health effects and acceptability were assessed through structured interviews and focus group discussions. Data were coded and analyzed using a thematic approach. In total, 262 interviews and 11 focus groups were conducted from 43 women. Overall, women preferred the ICS over the traditional three-stone fire for various reasons including ease of use, efficiency, fuel efficiency and perceived reduction in smoke and improved health. However, there were clear preferences for specific ICS with almost half of women preferring a Philips stove. Despite acceptance and use of ICS, women used multiple stoves to meet their daily needs. Qualitative studies are essential to field evaluations to provide insight into user perspectives and acceptability of ICS and to inform research and development of technologies that are both effective in reducing HAP and practical in use. PMID- 26828507 TI - Seasonal Shifts in Primary Water Source Type: A Comparison of Largely Pastoral Communities in Uganda and Tanzania. AB - Many water-related illnesses show an increase during the wet season. This is often due to fecal contamination from runoff, yet, it is unknown whether seasonal changes in water availability may also play a role in increased illness via changes in the type of primary water source used by households. Very little is known about the dynamic aspects of access to water and changes in source type across seasons, particularly in semi-arid regions with annual water scarcity. The research questions in this study were: (1) To what degree do households in Uganda (UG) and Tanzania (TZ) change primary water source type between wet and dry seasons?; and (2) How might seasonal changes relate to water quality and health? Using spatial survey data from 92 households each in UG and TZ this study found that, from wet to dry season, 26% (UG) and 9% (TZ) of households switched from a source with higher risk of contamination to a source with lower risk. By comparison, only 20% (UG) and 0% (TZ) of households switched from a source with lower risk of contamination to a source with higher risk of contamination. This research suggests that one pathway through which water-related disease prevalence may differ across seasons is the use of water sources with higher risk contamination, and that households with access to sources with lower risks of contamination sometimes choose to use more contaminated sources. PMID- 26828508 TI - Environmental Change in the Agro-Pastoral Transitional Zone, Northern China: Patterns, Drivers, and Implications. AB - Chengde city is located in the agro-pastoral transitional zone in northern China near the capital city of Beijing, which has experienced large-scale ecological construction in the past three decades. This study quantitatively assessed the environmental changes in Chengde through observation records of water resources, water environment, atmospheric environment, and vegetation activity and investigated the possible causes. From the late 1950s to 2002, the streamflow presented a downward trend induced by climate variability and human activities, with contribution ratios of 33.2% and 66.8%, respectively. During 2001-2012, the days of levels I and II air quality presented clear upward trends. Moreover, the air pollutant concentration was relatively low compared with that in the adjacent areas, which means the air quality has improved more than that in the neighboring areas. The water quality, which deteriorated during 1993-2000, began to improve in 2002. The air and water quality changes were closely related to pollutant emissions induced by anthropogenic activities. During 1982-2012, the vegetation in the southeastern and central regions presented restoration trends, whereas that in the northwestern area showed degradation trends. The pixels with obvious degradation trends correlated significantly with annual mean temperature and annual precipitation. Ecological engineering also played a positive role in vegetation restoration. This analysis can be beneficial to environment managers in the active response and adaptation to the possible effects of future climate change, population growth, and industrial development and can be used to ensure sustainable development and environmental safety. PMID- 26828506 TI - Biomarker-Based Approaches for Assessing Alcohol Use Disorders. AB - Although alcohol use disorders rank among the leading public health problems worldwide, hazardous drinking practices and associated morbidity continue to remain underdiagnosed. It is postulated here that a more systematic use of biomarkers improves the detection of the specific role of alcohol abuse behind poor health. Interventions should be initiated by obtaining information on the actual amounts of recent alcohol consumption through questionnaires and measurements of ethanol and its specific metabolites, such as ethyl glucuronide. Carbohydrate-deficient transferrin is a valuable tool for assessing chronic heavy drinking. Activities of common liver enzymes can be used for screening ethanol induced liver dysfunction and to provide information on the risk of co morbidities including insulin resistance, metabolic syndrome and vascular diseases. Conventional biomarkers supplemented with indices of immune activation and fibrogenesis can help to assess the severity and prognosis of ethanol-induced tissue damage. Many ethanol-sensitive biomarkers respond to the status of oxidative stress, and their levels are modulated by factors of life style, including weight gain, physical exercise or coffee consumption in an age- and gender-dependent manner. Therefore, further attention should be paid to defining safe limits of ethanol intake in various demographic categories and establishing common reference intervals for biomarkers of alcohol use disorders. PMID- 26828510 TI - Factors Associated with Relapse among Heroin Addicts: Evidence from a Two-Year Community-Based Follow-Up Study in China. AB - BACKGROUND: Many countries including China are facing a serious opiate dependence problem. Anti-drug work effectiveness was affected by the high relapse rate all over the world. This study aims to analyze the factors influencing heroin addict relapse, and to provide evidence for generating relapse prevention strategies. METHODS: A community-based follow-up study was conducted in China between October 2010 and September 2012. A total of 554 heroin addicts in accordance with the inclusion criteria from 81 streets in 12 districts of Shanghai, China were divided into 4 groups: group 1--daily dosage taken orally of 60 mL of methadone or under combined with psychological counseling and social supports (n = 130); group 2--daily dosage taken orally of over 60 mL of methadone combined with psychological counseling and social supports (n = 50); group 3--JTT (Jitai tablets) combined with psychological counseling and social supports (n = 206); group 4--JTT combined with social supports (n = 168). RESULTS: Log-rank test results showed that the cumulative relapse rate differences among four groups during the two-year follow-up period were not statistically significant (chi2 = 5.889, p = 0.117). Multivariate Cox regression analysis results showed that only three independent variables were still statistically significant, including compliance with participation in psychological counseling (OR = 3.563, p = 0.000), the years of drug use (OR = 1.078, p = 0.001)and intervention model. CONCLUSIONS: Using the detoxification medications combined with appropriate psychological counseling and social support measures will help improve the effectiveness of relapse prevention, which is a kind of alternative community detoxification pattern. Appropriate and standard psychological counseling is very important for anti-drug treatment. The longer the drug addiction lasts, the longer the anti-drug treatment takes. PMID- 26828509 TI - Interactions of Six SNPs in ABCA1gene and Obesity in Low HDL-C Disease in Kazakh of China. AB - OBJECTIVE: To detect the interactions between six functional polymorphisms in ABCA1 and obesity in Kazakhs with low HDL-C levels. METHODS: A total of 204 patients with low HDL-C and 207 health control subjects, which were randomly selected from among 5692 adult Kazakhs, were matched for age and sex. We genotyped ABCA1 single nucleotide polymorphisms of rs2515602, rs3890182, rs2275542, rs2230806, rs1800976, and rs4149313. RESULTS: (1) The genotypic and allelic frequencies of rs2515602, rs2230806 and rs4149313 were different between normal HDL-C and low HDL-C subjects, the genotypic frequency of rs2275542 was also different between normal HDL-C and low HDL-C subjects (p < 0.05); (2) the level of HDL-C (rs2515602 and rs2275542) in normal HDL-C subjects were different among the genotypes (p < 0.05); the levels of TC, LDL-C (rs2515602, rs4149313); TG (rs2515602, rs1800976, rs4149313) in low HDL-C patients were different among the genotypes (p < 0.05); (3) interactions between the rs3890182, rs2275542, rs180096, and rs4149313 polymorphisms in ABCA1 gene and obesity may be associated with low HDL-C disease; (4) the C-C-C-A-A-G, T-C-C-A-A-A, T-C-C-A-A-G, C-C-C-A-A A, C-T-G-G-A-A, and T-T-C-G-A-A haplotypes were significant between the subjects with normal HDL-C and low HDL-C level (p < 0.05). CONCLUSIONS: The differences in serum lipid levels between normal HDL-C and low HDL-C subjects among Kazakhs might partly result from ABCA1 gene polymorphisms; ABCA1 gene polymorphisms may be associated with low HDL-C disease; the low HDL-C disease might partly result from interactions between ABCA1 gene polymorphisms and obesity; the C-C-C-A-A-G, T-C-C-A-A-A, and T-C-C-A-A-G haplotypes may serve as risk factors of low HDL-C disease among Kazakhs, the C-C-C-A-A-A, C-T-G-G-A-A, and T-T-C-G-A-A haplotypes may serve as protective factor of low HDL-C disease among Kazakhs. PMID- 26828511 TI - Association between Floods and Acute Cardiovascular Diseases: A Population-Based Cohort Study Using a Geographic Information System Approach. AB - BACKGROUND: Floods represent a serious threat to human health beyond the immediate risk of drowning. There is few data on the potential link between floods and direct consequences on health such as on cardiovascular health. This study aimed to explore the impact of one of the worst floods in the history of Quebec, Canada on acute cardiovascular diseases (CVD). METHODS: A cohort study with a time series design with multiple control groups was built with the adult population identified in the Quebec Integrated Chronic Disease Surveillance System. A geographic information system approach was used to define the study areas. Logistic regressions were performed to compare the occurrence of CVD between groups. RESULTS: The results showed a 25%-27% increase in the odds in the flooded population in spring 2011 when compared with the population in the same area in springs 2010 and 2012. Besides, an increase up to 69% was observed in individuals with a medical history of CVD. CONCLUSION: Despite interesting results, the association was not statistically significant. A possible explanation to this result can be that the population affected by the flood was probably too small to provide the statistical power to answer the question, and leaves open a substantial possibility for a real and large effect. PMID- 26828512 TI - Child Wasting in Emergency Pockets: A Meta-Analysis of Small-Scale Surveys from Ethiopia. AB - Child undernutrition is a major public health concern in Ethiopia (stunting national prevalence: 44%; wasting: 10%), despite the overall improvement in child health status during the last decade. Hundreds of small-scale surveys are conducted in Ethiopia's emergency pockets under ENCU's supervision. We reviewed the evidence from small-scale surveys conducted between 2008 and 2013 with two objectives: to provide a summary estimate of wasting prevalence from emergency pockets and to examine reasons for variation in prevalence estimates. We created a dataset by combining data from the Complex Emergency Database, the Famine Early Warning System Network and the Armed Conflict Location Event Data. We conducted a meta-analysis of small-scale surveys using a random effects model with known within-study heterogeneity. The influence of survey covariates on estimated prevalence was investigated with meta-regression techniques. We included 158 surveys in the analysis. A high degree of heterogeneity among surveys was observed. The overall estimate of wasting prevalence was 10.6% (95% CI 9.8-11.4), with differences among regions and between residents and refugees. Meta regression results showed that vaccination coverage, child mortality, diarrhea prevalence and food insecurity are significantly associated with wasting prevalence. Child care and displacement status were not. Aggregated analysis of small-scale surveys provides insights into the prevalence of wasting and factors explaining its variation. It can also guide survey planning towards areas with limited data availability. PMID- 26828514 TI - The Autophagic Machinery in Enterovirus Infection. AB - The Enterovirus genus of the Picornaviridae family comprises many important human pathogens, including polioviruses, rhinovirus, enterovirus A71, and enterovirus D68. They cause a wide variety of diseases, ranging from mild to severe life threatening diseases. Currently, no effective vaccine is available against enteroviruses except for poliovirus. Enteroviruses subvert the autophagic machinery to benefit their assembly, maturation, and exit from host. Some enteroviruses spread between cells via a process described as autophagosome mediated exit without lysis (AWOL). The early and late phases of autophagy are regulated through various lipids and their metabolizing enzymes. Some of these lipids and enzymes are specifically regulated by enteroviruses. In the present review, we summarize the current understanding of the regulation of autophagic machinery by enteroviruses, and provide updates on recent developments in this field. PMID- 26828515 TI - Iron-Folic Acid Supplementation During Pregnancy Reduces the Risk of Stunting in Children Less Than 2 Years of Age: A Retrospective Cohort Study from Nepal. AB - The aim of the study was to investigate the effect of antenatal iron-folic acid (IFA) supplementation on child stunting in Nepalese children age <2 years. A retrospective cohort study design was used, in which a pooled cohort of 5235 most recent live births 2 years prior to interview from three Nepal Demographic and Health Surveys (2001, 2006 and 2011) was analysed. The primary outcome was stunting in children age <2 years. The main exposure variable was antenatal IFA supplementation. Multivariate Poisson regression analysis was performed. In our sample, 31% and 10% of Nepalese children age <2 years were stunted and severely stunted, respectively. The adjusted relative risk of being stunted was 14% lower in children whose mothers used IFA supplements compared to those whose mothers did not use (aRR = 0.86, 95% CI = 0.77-0.97). Additionally, the adjusted relative risk of being stunted was significantly reduced by 23% when antenatal IFA supplementation was started <=6 months with >=90 IFA supplements used during pregnancy (aRR = 0.77, 95% CI = 0.64-0.92). Antenatal IFA supplementation significantly reduced the risk of stunting in Nepalese children age <2 years. The greatest impact on the risk reduction of child stunting was when IFA supplements were started <=6 months with >=90 supplements were used. PMID- 26828513 TI - Molecular Studies of HTLV-1 Replication: An Update. AB - Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus discovered. Studies on HTLV-1 have been instrumental for our understanding of the molecular pathology of virus-induced cancers. HTLV-1 is the etiological agent of an adult T-cell leukemia (ATL) and can lead to a variety of neurological pathologies, including HTLV-1-associated-myelopathy/tropical spastic paraparesis (HAM/TSP). The ability to treat the aggressive ATL subtypes remains inadequate. HTLV-1 replicates by (1) an infectious cycle involving virus budding and infection of new permissive target cells and (2) mitotic division of cells harboring an integrated provirus. Virus replication initiates host antiviral immunity and the checkpoint control of cell proliferation, but HTLV-1 has evolved elegant strategies to counteract these host defense mechanisms to allow for virus persistence. The study of the molecular biology of HTLV-1 replication has provided crucial information for understanding HTLV-1 replication as well as aspects of viral replication that are shared between HTLV-1 and human immunodeficiency virus type 1 (HIV-1). Here in this review, we discuss the various stages of the virus replication cycle-both foundational knowledge as well as current updates of ongoing research that is important for understanding HTLV-1 molecular pathogenesis as well as in developing novel therapeutic strategies. PMID- 26828516 TI - Anorexia of Aging: Risk Factors, Consequences, and Potential Treatments. AB - Older people frequently fail to ingest adequate amount of food to meet their essential energy and nutrient requirements. Anorexia of aging, defined by decrease in appetite and/or food intake in old age, is a major contributing factor to under-nutrition and adverse health outcomes in the geriatric population. This disorder is indeed highly prevalent and is recognized as an independent predictor of morbidity and mortality in different clinical settings. Even though anorexia is not an unavoidable consequence of aging, advancing age often promotes its development through various mechanisms. Age-related changes in life-style, disease conditions, as well as social and environmental factors have the potential to directly affect dietary behaviors and nutritional status. In spite of their importance, problems related to food intake and, more generally, nutritional status are seldom attended to in clinical practice. While this may be the result of an "ageist" approach, it should be acknowledged that simple interventions, such as oral nutritional supplementation or modified diets, could meaningfully improve the health status and quality of life of older persons. PMID- 26828518 TI - Total, Free, and Added Sugar Consumption and Adherence to Guidelines: The Dutch National Food Consumption Survey 2007-2010. AB - A high sugar intake is a subject of scientific debate due to the suggested health implications and recent free sugar recommendations by the WHO. The objective was to complete a food composition table for added and free sugars, to estimate the intake of total sugars, free sugars, and added sugars, adherence to sugar guidelines and overall diet quality in Dutch children and adults. In all, 3817 men and women (7-69 years) from the Dutch National Food Consumption Survey 2007 2010 were studied. Added and free sugar content of products was assigned by food composition tables and using labelling and product information. Diet was assessed with two 24-h recalls. Diet quality was studied in adults with the Dutch Healthy Diet-index. Total sugar intake was 22% Total Energy (%TE), free sugars intake 14 %TE, and added sugar intake 12 %TE. Sugar consumption was higher in children than adults. Main food sources of sugars were sweets and candy, non-alcoholic beverages, dairy, and cake and cookies. Prevalence free sugar intake <10 %TE was 5% in boys and girls (7-18 years), 29% in women, and 33% in men. Overall diet quality was similar comparing adults adherent and non-adherent to the sugar guidelines, although adherent adults had a higher intake of dietary fiber and vegetables. Adherence to the WHO free sugar guidelines of <5 %TE and <10 %TE was generally low in the Netherlands, particularly in children. Adherence to the added and free sugar guidelines was not strongly associated with higher diet quality in adults. PMID- 26828519 TI - Association of Body Composition with Curve Severity in Children and Adolescents with Idiopathic Scoliosis (IS). AB - The link between scoliotic deformity and body composition assessed with bioimpedance (BIA) has not been well researched. The objective of this study was to correlate the extent of scoliotic-curve severity with the anthropometrical status of patients with idiopathic scoliosis (IS) based on standard anthropometric measurements and BIA. The study encompassed 279 IS patients (224 girls/55 boys), aged 14.21 +/- 2.75 years. Scoliotic curve severity assessed by Cobb's angle was categorized as moderate (10 degrees -39 degrees ) or severe (>=40 degrees ). Corrected height, weight, waist and hip circumferences were measured and body mass index (BMI), corrected height z-score, BMI Z-score, waist/height ratio (WHtR) and waist/hip ratio (WHR) were calculated for the entire group. Body composition parameters: fat mass (FAT), fat-free mass (FFM) and predicted muscle mass (PMM) were determined using a bioelectrical impedance analyzer. The mean Cobb angle was 19.96 degrees +/- 7.92 degrees in the moderate group and 52.36 degrees +/- 12.54 degrees in the severe group. The corrected body heights, body weights and BMIs were significantly higher in the severe IS group than in the moderate group (p < 0.05). Significantly higher FAT and lower FFM and PMM were observed in the severe IS group (p < 0.05). The corrected heights and weights were significantly higher in patients with severe IS and normal weight (p < 0.01). Normal and overweight patients with a severe IS had significantly higher adiposity levels assessed by FAT, FFM and PMM for normal and BMI, BMI z-score, WHtR, FAT and PMM for overweight, respectively. Overweight IS patients were significantly younger and taller than underweight and normal weight patients. The scoliotic curve severity is significantly related to the degree of adiposity in IS patients. BMI z-score, WHtR and BIA seem to be useful tools for determining baseline anthropometric characteristics of IS children. PMID- 26828517 TI - B Vitamins and the Brain: Mechanisms, Dose and Efficacy--A Review. AB - The B-vitamins comprise a group of eight water soluble vitamins that perform essential, closely inter-related roles in cellular functioning, acting as co enzymes in a vast array of catabolic and anabolic enzymatic reactions. Their collective effects are particularly prevalent to numerous aspects of brain function, including energy production, DNA/RNA synthesis/repair, genomic and non genomic methylation, and the synthesis of numerous neurochemicals and signaling molecules. However, human epidemiological and controlled trial investigations, and the resultant scientific commentary, have focused almost exclusively on the small sub-set of vitamins (B9/B12/B6) that are the most prominent (but not the exclusive) B-vitamins involved in homocysteine metabolism. Scant regard has been paid to the other B vitamins. This review describes the closely inter-related functions of the eight B-vitamins and marshals evidence suggesting that adequate levels of all members of this group of micronutrients are essential for optimal physiological and neurological functioning. Furthermore, evidence from human research clearly shows both that a significant proportion of the populations of developed countries suffer from deficiencies or insufficiencies in one or more of this group of vitamins, and that, in the absence of an optimal diet, administration of the entire B-vitamin group, rather than a small sub-set, at doses greatly in excess of the current governmental recommendations, would be a rational approach for preserving brain health. PMID- 26828521 TI - Molecular Characteristic, Protein Distribution and Potential Regulation of HSP90AA1 in the Anadromous Fish Coilia nasus. AB - Heat shock proteins play essential roles in basic cellular events. Spawning migration is a complex process, with significant structural and biochemical changes taking place in the adult gonad. To date, the molecular mechanisms underlying migration reproductive biology remain undetermined. In this regard, a full length HSP90AA1 comprising 2608 nucleotides from the anadromous fish Coilia nasus was characterized, encoding 742 amino acid (aa) residues with potential phosphorylation sites. HSP90AA1 mRNA transcripts were detected in all organs, especially in the gonad. Furthermore, the greatest transcript levels were found during the developmental phase, while the lowest levels were found during the resting phase. In addition, the strongest immunolabeling positive signal was found in the primary spermatocyte and oocyte, with lower positive staining in secondary germ cells, and a weak or absent level in the mature sperm and oocyte. Interestingly, HSP90AA1 was mainly located in the cytoplasm of germ cells. These results are important for understanding the molecular mechanism of anadromous migration reproductive biology. In combination with data from other fish species, the result of this present study may facilitate further investigations on the spawning migration mechanism. PMID- 26828520 TI - Breast Cancer-Associated Fibroblasts: Where We Are and Where We Need to Go. AB - Cancers are heterogeneous tissues comprised of multiple components, including tumor cells and microenvironment cells. The tumor microenvironment has a critical role in tumor progression. The tumor microenvironment is comprised of various cell types, including fibroblasts, macrophages and immune cells, as well as extracellular matrix and various cytokines and growth factors. Fibroblasts are the predominant cell type in the tumor microenvironment. However, neither the derivation of tissue-specific cancer-associated fibroblasts nor markers of tissue specific cancer-associated fibroblasts are well defined. Despite these uncertainties it is increasingly apparent that cancer-associated fibroblasts have a crucial role in tumor progression. In breast cancer, there is evolving evidence showing that breast cancer-associated fibroblasts are actively involved in breast cancer initiation, proliferation, invasion and metastasis. Breast cancer associated fibroblasts also play a critical role in metabolic reprogramming of the tumor microenvironment and therapy resistance. This review summarizes the current understanding of breast cancer-associated fibroblasts. PMID- 26828522 TI - The Changing Landscape of Molecular Diagnostic Testing: Implications for Academic Medical Centers. AB - Over the last decade, the field of molecular diagnostics has undergone tremendous transformation, catalyzed by the clinical implementation of next generation sequencing (NGS). As technical capabilities are enhanced and current limitations are addressed, NGS is increasingly capable of detecting most variant types and will therefore continue to consolidate and simplify diagnostic testing. It is likely that genome sequencing will eventually serve as a universal first line test for disorders with a suspected genetic origin. Academic Medical Centers (AMCs), which have been at the forefront of this paradigm shift are now presented with challenges to keep up with increasing technical, bioinformatic and interpretive complexity of NGS-based tests in a highly competitive market. Additional complexity may arise from altered regulatory oversight, also triggered by the unprecedented scope of NGS-based testing, which requires new approaches. However, these challenges are balanced by unique opportunities, particularly at the interface between clinical and research operations, where AMCs can capitalize on access to cutting edge research environments and establish collaborations to facilitate rapid diagnostic innovation. This article reviews present and future challenges and opportunities for AMC associated molecular diagnostic laboratories from the perspective of the Partners HealthCare Laboratory for Molecular Medicine (LMM). PMID- 26828523 TI - Novel Strategies in the Prevention and Treatment of Urinary Tract Infections. AB - Urinary tract infections are one of the most common bacterial infections, especially in women and children, frequently treated with antibiotics. The alarming increase in antibiotic resistance is a global threat to future treatment of infections. Therefore, alternative strategies are urgently needed. The innate immune system plays a fundamental role in protecting the urinary tract from infections. Antimicrobial peptides form an important part of the innate immunity. They are produced by epithelial cells and neutrophils and defend the urinary tract against invading bacteria. Since efficient resistance mechanisms have not evolved among bacterial pathogens, much effort has been put into exploring the role of antimicrobial peptides and possibilities to utilize them in clinical practice. Here, we describe the impact of antimicrobial peptides in the urinary tract and ways to enhance the production by hormones like vitamin D and estrogen. We also discuss the potential of medicinal herbs to be used in the prophylaxis and the treatment of urinary tract infections. PMID- 26828524 TI - Importance of B Lymphocytes and the IgG-Binding Protein Sbi in Staphylococcus aureus Skin Infection. AB - Recurrent Staphylococcus aureus infections are common, suggesting that immunity elicited by these infections is not protective. We previously reported that S. aureus skin infection (SSTI) elicited antibody-mediated immunity against secondary SSTI in BALB/c mice. In this study, we investigated the role of humoral immunity and the IgG-binding proteins Sbi and SpA in S. aureus SSTI. We found that B lymphocyte-deficient MUMT mice were highly susceptible to infection, compared with congenic BALB/c mice. Importantly, transfer of immune serum protected MUMT mice, demonstrating an appropriate response to protective antibody. We found that deletion of sbi, but not spa, impaired virulence, as assessed by skin lesion severity, and that Sbi-mediated virulence required B lymphocytes/antibody. Furthermore, neither Sbi nor SpA impaired the elicited antibody response or protection against secondary SSTI. Taken together, these findings highlight a B lymphocyte/antibody-dependent role of Sbi in the pathogenesis of S. aureus SSTI, and demonstrate that neither Sbi nor SpA interfered with elicited antibody-mediated immunity. PMID- 26828525 TI - Proton Conductivity of Nafion/Ex-Situ Sulfonic Acid-Modified Stober Silica Nanocomposite Membranes As a Function of Temperature, Silica Particles Size and Surface Modification. AB - The introduction of sulfonic acid modified silica in Nafion nanocomposite membranes is a good method of improving the Nafion performance at high temperature and low relative humidity. Sulfonic acid-modified silica is bifunctional, with silica phase expected to offer an improvement in membranes hydration while sulfonic groups enhance proton conductivity. However, as discussed in this paper, this may not always be the case. Proton conductivity enhancement of Nafion nanocomposite membranes is very dependent on silica particle size, sometimes depending on experimental conditions, and by surface modification. In this study, Sulfonated Preconcentrated Nafion Stober Silica composites (SPNSS) were prepared by modification of Stober silica particles with mercaptopropyltriethoxysilane, dispersing the particles into a preconcentrated solution of Nafion, then casting the membranes. The mercapto groups were oxidized to sulfonic acids by heating the membranes in 10 wt % hydrogen peroxide for 1 h. At 80 degrees C and 100% relative humidity, a 20%-30% enhancement of proton conductivity was only observed when sulfonic acid modified particle less than 50 nm in diameter were used. At 120 degrees C, and 100% humidity, proton conductivity increased by 22%-42% with sulfonated particles with small particles showing the greatest enhancement. At 120 degrees C and 50% humidity, the sulfonated particles are less efficient at keeping the membranes hydrated, and the composites underperform Nafion and silica-Nafion nanocomposite membranes. PMID- 26828527 TI - Mechanisms Involved in the Improvement of Lipotoxicity and Impaired Lipid Metabolism by Dietary alpha-Linolenic Acid Rich Salvia hispanica L (Salba) Seed in the Heart of Dyslipemic Insulin-Resistant Rats. AB - This study explores the mechanisms underlying the altered lipid metabolism in the heart of dyslipemic insulin-resistant (IR) rats fed a sucrose-rich diet (SRD) and investigates if chia seeds (rich in alpha-linolenic acid 18:3, n-3 ALA) improve/reverse cardiac lipotoxicity. Wistar rats received an SRD-diet for three months. Half of the animals continued with the SRD up to month 6. The other half was fed an SRD in which the fat source, corn oil (CO), was replaced by chia seeds from month 3 to 6 (SRD+chia). A reference group consumed a control diet (CD) all the time. Triglyceride, long-chain acyl CoA (LC ACoA) and diacylglycerol (DAG) contents, pyruvate dehydrogenase complex (PDHc) and muscle-type carnitine palmitoyltransferase 1 (M-CPT1) activities and protein mass levels of M-CPT1, membrane fatty acid transporter (FAT/CD36), peroxisome proliferator activated receptor alpha (PPARalpha) and uncoupling protein 2 (UCP2) were analyzed. Results show that: (a) the hearts of SRD-fed rats display lipotoxicity suggesting impaired myocardial lipid utilization; (b) Compared with the SRD group, dietary chia normalizes blood pressure; reverses/improves heart lipotoxicity, glucose oxidation, the increased protein mass level of FAT/CD36, and the impaired insulin stimulated FAT/CD36 translocation to the plasma membrane. The enhanced M-CPT1 activity is markedly reduced without similar changes in protein mass. PPARalpha slightly decreases, while the UCP2 protein level remains unchanged in all groups. Normalization of dyslipidemia and IR by chia reduces plasma fatty acids (FAs) availability, suggesting that a different milieu prevents the robust translocation of FAT/CD36. This could reduce the influx of FAs, decreasing the elevated M-CPT1 activity and lipid storage and improving glucose oxidation in cardiac muscles of SRD-fed rats. PMID- 26828526 TI - Role of EMT in Metastasis and Therapy Resistance. AB - Epithelial-mesenchymal transition (EMT) is a complex molecular program that regulates changes in cell morphology and function during embryogenesis and tissue development. EMT also contributes to tumor progression and metastasis. Cells undergoing EMT expand out of and degrade the surrounding microenvironment to subsequently migrate from the primary site. The mesenchymal phenotype observed in fibroblasts is specifically important based on the expression of smooth muscle actin (alpha-SMA), fibroblast growth factor (FGF), fibroblast-specific protein-1 (FSP1), and collagen to enhance EMT. Although EMT is not completely dependent on EMT regulators such as Snail, Twist, and Zeb-1/-2, analysis of upstream signaling (i.e., TGF-beta, EGF, Wnt) is necessary to understand tumor EMT more comprehensively. Tumor epithelial-fibroblast interactions that regulate tumor progression have been identified during prostate cancer. The cellular crosstalk is significant because these events influence therapy response and patient outcome. This review addresses how canonical EMT signals originating from prostate cancer fibroblasts contribute to tumor metastasis and recurrence after therapy. PMID- 26828528 TI - Visualization of Microfloral Metabolism for Marine Waste Recycling. AB - Marine biomass including fishery products are precious protein resources for human foods and are an alternative to livestock animals in order to reduce the virtual water problem. However, a large amount of marine waste can be generated from fishery products and it is not currently recycled. We evaluated the metabolism of digested marine waste using integrated analytical methods, under anaerobic conditions and the fertilization of abandoned agricultural soils. Dynamics of fish waste digestion revealed that samples of meat and bony parts had similar dynamics under anaerobic conditions in spite of large chemical variations in input marine wastes. Abandoned agricultural soils fertilized with fish waste accumulated some amino acids derived from fish waste, and accumulation of l arginine and l-glutamine were higher in plant seedlings. Therefore, we have proposed an analytical method to visualize metabolic dynamics for recycling of fishery waste processes. PMID- 26828529 TI - The effects of pre-analysis sample handling on human plasma amino acid concentrations. AB - BACKGROUND: The accurate and reliable quantification of amino acid concentrations in human plasma is important for the investigation of a number of diseases. However, few systematic studies investigating the changes in amino acid concentrations related to blood collection and storage conditions have been completed. METHODS: Blood samples were collected with EDTA-Na2 from 3 healthy volunteers and subjected to a number of different treatments; hemolysis, temperature after blood collection, time from blood collection to cooling, the influence of platelets, long term storage conditions, and repeated freeze-thaw cycles. Changes in the concentrations of 22 amino acids were determined using an Amino Acid Analyzer. RESULTS: Of the conditions influencing sample stability between blood collection and amino acid analysis, hemolysis, temperature after blood collection, and long-term storage at -20 degrees C affected the concentrations of 11 amino acids. Time from blood collection to cooling, platelet contamination and repeated freeze-thaw cycles altered the levels of 4 amino acids. CONCLUSIONS: We observed changes in amino acid concentrations relating to blood collection and storage conditions. If attention is paid to 4 key factors (hemolysis, temperature immediately following blood collection, time from collection to cooling, and long-term storage temperature) 19 amino acids can be reliably quantified. PMID- 26828530 TI - Effects of hemoglobin C, D, E and S traits on measurements of hemoglobin A1c by twelve methods. AB - BACKGROUND: Hemoglobin C, D Punjab, E or S trait can interfere with hemoglobin A1c (HbA1c) results. We assessed whether they affect results obtained with 12 current assay methods. METHODS: Hemoglobin AA (HbAA), HbAC, HbAD Punjab, HbAE and HbAS samples were analyzed on one enzymatic, nine ion-exchange HPLC and two Capillary Electrophoresis methods. Trinity ultra(2) boronate affinity HPLC was the comparative method. An overall test of coincidence of least-squared linear regression lines was performed to determine if HbA1c results were statistically significantly different from those of HbAA samples. Clinically significant interference was defined as >7% difference from HbAA at 6 or 9% HbA1c compared to ultra(2) using Deming regression. RESULTS: All methods showed statistically significant effects for one or more variants. Clinically significant effects were observed for the Tosoh G8 variant mode and GX (all variants), GX V1.22 (all but HbAE) and G11 variant mode (HbAC). All other methods (Abbott Architect c Enzymatic, Bio-Rad D-100, Variant II NU and Variant II Turbo 2.0, Menarini HA 8180T thalassemia mode and HA-8180V variant mode, Sebia Capillarys 2 and Capillarys 3) showed no clinically significant differences. CONCLUSIONS: Several methods showed clinically significant interference with HbA1c results from one or more variants which could adversely affect patient care. PMID- 26828531 TI - Unrecognized myocardial infarctions detected by cardiac magnetic resonance imaging are associated with cardiac troponin I levels. AB - BACKGROUND: Both unrecognized myocardial infarction (UMI) and elevated levels of biomarkers are common in patients with stable coronary artery disease (CAD). The objective of this study was to determine the association between levels of cardiac biomarkers, UMI and extent of CAD in patients with stable CAD. METHODS: A total of 235 patients (median age: 65years; 34% women) with stable CAD without previously known myocardial infarction were examined with late gadolinium enhancement cardiovascular magnetic resonance imaging and coronary angiography. Blood samples were drawn at enrolment and high sensitivity cardiac troponin I (cTnI), NT-proBNP and Galectin-3 were analyzed. RESULTS: UMI was detected in 58 patients (25%). The median levels of cTnI, NT-proBNP and Galectin-3 were significantly higher in patients with UMI compared to those without, (p<0.001, p=0.006 and p=0.033, respectively). After adjustment for cardiovascular risk factors, left ventricular ejection fraction and renal function, cTnI remained independently associated with the presence of UMI (p=0.031) and the extent of CAD (p=0.047). Neither NT-proBNP, nor Galectin-3, was independently associated with UMI or extent of CAD. CONCLUSIONS: The independent association between levels of cTnI and UMI indicates a common pathophysiological pathway for the cTnI elevation and development of UMI. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01257282). PMID- 26828532 TI - Novel large deletion in AVPR2 gene causing copy number variation in a patient with X-linked nephrogenic diabetes insipidus. AB - BACKGROUND: The diagnosis of cranial and nephrogenic diabetes insipidus (DI) can be clinically challenging. The application of molecular genetic analysis can help in resolving diagnostic difficulties. CASE: A 3 month-old boy presented with recurrent polyuria was admitted to Intensive Care Unit and was treated as DI. The patient also had a strong family history of polyuria affecting his maternal uncles. Molecular genetic analysis using Single Nucleotide Polymorphism (SNP) array detected a large deletion located at Xq28 region and the breakpoint was identified using PCR and Sanger sequencing. An 11,535 bp novel deletion affecting the entire APVR2 gene and the last intron and exon of the ARHGAP4 gene was confirmed. This large deletion is likely due to the 7-bp microhomology sequence at the junctions of both 5' and 3' breakpoints. No disease-causing mutation was identified for AQP2. CONCLUSION: We report a novel deletion in a Chinese patient with congenital nephrogenic DI. We suggested that patients with suspected congenital DI should undergo genetic analysis of AVPR2 and AQP2 genes. A definitive diagnosis can benefit patient by treatment of hydrochlorothiazide and amiloride and avoiding unnecessary investigations. PMID- 26828533 TI - Alteration of serum semaphorin 3B levels in preeclampsia. AB - BACKGROUND: Placental Semaphorin 3B (SEMA 3B) expression has been reported changed in preeclampsia and its possible involvement of in the disease proposed. We clarified the alterations of maternal SEMA 3B level in women suffering preeclampsia and pregnant women at gestational weeks of 16-20 before the onset of preeclampsia. METHODS: Serum SEMA 3B concentration was measured with ELISA in preeclamptic women (preeclampsia) and normotensive women (control) in 3rd trimester, and also in pregnant women at gestational weeks of 16-20 who developed preeclampsia or had favorable pregnant outcome. RESULTS: Serum SEMA 3B level was significantly increased in preeclampsia compared with control (P<0.001). There was a significant difference in serum SEMA 3B between mild and severe preeclampsia (P=0.04). Women with severe preeclampsia had significant serum SEMA 3B than women with mild preeclampsia. At gestational weeks of 16-20, serum SEMA 3B was significantly higher in women who developed preeclampsia than women who had normal pregnant outcome (P<0.001). CONCLUSIONS: Maternal SEMA 3B level increased in preeclampsia before the onset of manifestations, indicating that SEMA 3B plays a role in the pathogenesis of preeclampsia. PMID- 26828534 TI - The relationship between cholesterol concentration and carotid intima media thickness differs according to gender and menopausal status in Korean type 2 diabetic patients. AB - BACKGROUND: We investigated the associations between cardiometabolic factors and carotid intima media thickness (IMT) in Korea type 2 diabetes (T2DM) patients, and assessed the possible difference with respect to gender and menopausal status. METHODS: We conducted a cross-sectional study with 1288 T2DM patients from the Department of Endocrinology and Metabolism at Gangnam Severance Hospital. Carotid IMT and various biochemical parameters were measured, and the postmenopausal status was assessed. RESULTS: In partial correlation analysis, total cholesterol (TC) and LDL cholesterol (LDL-C) were positively correlated with right maximum IMT in men. For postmenopausal women, TC and LDL-C were positively correlated with IMT (all p<0.05) while no such correlation was observed in premenopausal women. In regression analysis, age was the most predominant factor for IMT in all 3 groups. For men, insulin and TC were predictive factors for maximum IMT (all p<0.05), and for postmenopausal women, TC and LDL-C were significant factors for mean and maximum IMT (all p<0.01). However, cholesterol concentrations were not related to all types of IMT in premenopausal women. CONCLUSION: The association between LDL-C and carotid IMT seems to differ according to gender and menopausal status in T2DM patients. PMID- 26828535 TI - High-throughput prediction of tablet weight and trimethoprim content of compound sulfamethoxazole tablets for controlling the uniformity of dosage units by NIR. AB - This paper establishes a novel method to simultaneously predict the tablet weight (TW) and trimethoprim (TMP) content of compound sulfamethoxazole tablets (SMZCO) by near infrared (NIR) spectroscopy with partial least squares (PLS) regression for controlling the uniformity of dosage units (UODU). The NIR spectra for 257 samples were measured using the optimized parameter values and pretreated using the optimized chemometric techniques. After the outliers were ignored, two PLS models for predicting TW and TMP content were respectively established by using the selected spectral sub-ranges and the reference values. The TW model reaches the correlation coefficient of calibration (R(c)) 0.9543 and the TMP content model has the R(c) 0.9205. The experimental results indicate that this strategy expands the NIR application in controlling UODU, especially in the high throughput and rapid analysis of TWs and contents of the compound pharmaceutical tablets, and may be an important complement to the common NIR on-line analytical method for pharmaceutical tablets. PMID- 26828538 TI - Matt Briggs: Medical Artists' Association Members Exhibition Award. PMID- 26828537 TI - Delafossite structure of heterogenite polytypes (HCoO2) by Raman and infrared micro-spectroscopy. AB - Heterogenite is commonly referred in mineralogy literature as a cobalt oxy hydroxide CoO(OH). However, detailed analysis of Raman and infrared spectra acquired on particularly well-crystallized natural samples of heterogenite suggests that the mineral can be characterized by a delafossite-type structure, with a general chemical formula ABO2. Indeed, the Raman spectrum of heterogenite, along the one with grimaldiite (HCrO2), lacks visible free OH-group vibrational modes, while the infrared spectrum shows strong hydrogen bond absorption bands. HCoO2 is thus a better formulation of heterogenite that describes more clearly its vibrational behavior and avoids the confusion in literature. Electronic backscattered diffraction (EBSD) is then used to distinguish and map the 2H and 3R heterogenite natural polytypes for the first time. The comparison of EBSD and Raman mappings clearly indicates that the 2H polytype is characterized by an additional peak at 1220 cm(-1). The presence/absence is therefore an efficient tool to distinguish both polytypes. PMID- 26828536 TI - The development of a new optical sensor based on the Mn doped ZnS quantum dots modified with the molecularly imprinted polymers for sensitive recognition of florfenicol. AB - The Mn doped ZnS quantum dots (Mn:ZnS QDs) capped with the florfenicol molecularly imprinted polymer (Mn:ZnS QDs@MIP) were prepared via the sol-gel surface imprinting approach using 3-aminopropyltriethoxysilane (APTES) as the functional monomer and tetraethoxysilane (TEOS) as the cross-linker for the optosensing of the florfenicol. Transmission electron microscopy (TEM), X-ray diffractometer, IR spectroscopy, UV-Vis absorption spectrophotometry, and spectrofluorometry were used to elucidate the formation, morphology, and identification of the products. To illustrate the usefulness of the new imprinted material, the non-imprinted coated Mn:ZnS QDs (Mn:ZnS QDs@NIP) were synthesized without the presence of the florfenicol. It was revealed that the fluorescence (FL) intensity of the Mn:ZnS QDs@MIP increased with increasing the FF concentration. Under the optimal conditions, changes in the FL intensity in the presence of the target molecule showed a linear response in the concentration range of 30-700 MUmol L(-1) with a detection limit of 24 MUmol L(-1). The developed method was finally applied successfully to the determination of FF in different meat samples with satisfactory recoveries. PMID- 26828539 TI - Editorial. PMID- 26828540 TI - Benchmarking clinical photography services in the NHS. AB - Benchmarking is used in services across the National Health Service (NHS) using various benchmarking programs. Clinical photography services do not have a program in place and services have to rely on ad hoc surveys of other services. A trial benchmarking exercise was undertaken with 13 services in NHS Trusts. This highlights valuable data and comparisons that can be used to benchmark and improve services throughout the profession. PMID- 26828541 TI - An introduction to OCT in retinal disease. AB - Ocular coherence tomography (OCT) has been available to ophthalmologists for many years and has had a significant impact on the diagnosis and treatment of many eye conditions. This fast and non-invasive way to image the eye has had a considerable effect on ophthalmic photography services. OCT can be used to assess the structure of the cornea, iris, anterior chamber, optic nerve and retina. This article focuses upon its use in retinal conditions and explores how the technique is used to aid treatment and diagnosis. PMID- 26828542 TI - Prescription play: A primer on innovative use of video games technology in healthcare. AB - As technology evolves it becomes increasingly accessible to the masses to own, develop for, and distribute global healthcare solutions with. In this paper the author presents a series of project case examples exemplifying current medical applications of new media and technology, with suggestions for potential areas of further research and development. The author encourages a multi-disciplinary approach for designing effective and engaging games to optimise delivery of medically useful content and therapeutic strategies. PMID- 26828543 TI - Living with psoriasis: a patient case study. AB - In summary, this patient has had a very positive experience with his UVB phototheapy treatment. The flaking of the skin has stopped which has made him less conscious in social situations and he is much more comfortable around other people. Being able to observe the improvement in his psoriasis through photography has increased the patient's confidence and he hopes that the improvement in his condition will continue. PMID- 26828544 TI - From analogue to apps--developing an app to prepare children for medical imaging procedures. AB - The Royal Children's Hospital (RCH) in Melbourne has launched a world-first app for children that will help reduce anxiety and the need for anesthesia during medical imaging procedures. The free, game-based app, "Okee in Medical Imaging", helps children aged from four to eight years to prepare for all medical imaging procedures--X-ray, CT, MRI, ultrasound, nuclear medicine, and fluoroscopy. The app is designed to reduce anticipatory fear of imaging procedures, while helping to ensure that children attend imaging appointments equipped with the skills required for efficient and effective scans to be performed. This paper describes how the app was developed. PMID- 26828545 TI - Playing with light, business alchemy and the quest for the magic formula: Greg Harding. PMID- 26828547 TI - Mirrors in early clinical photography (1862-1882): a descriptive study. AB - In the mid-nineteenth century, photographers used mirrors to document different views of a patient in the same image. The first clinical photographs were taken by portrait photographers. As conventions for clinical photography were not yet established, early clinical photographs resemble contemporary portraits. The use of mirrors in clinical photography probably originated from the portrait studios, as several renowned photographers employed mirrors in their studio portraits. Clinical photographs taken for the US Army Medical Museum between 1862 and 1882 show different ways of employing this mirror technique. PMID- 26828548 TI - The Adamson Collection: illustrations of mental illness or a testament to spontaneous artistic expression? PMID- 26828549 TI - Antique ophthalmic equipment at Bristol Eye Hospital. PMID- 26828550 TI - Victor Willmott--Britain's first medical photographer. PMID- 26828551 TI - The imaginarium of tears--Maurice Mikkers. PMID- 26828552 TI - Genetic portraits--Ulric Collette. PMID- 26828553 TI - The Hidden Beauty in Biomedical Imaging. AB - Caretakers, researchers and photographers working in a busy academic settings, every day are faced with images that are awe-inspiring for their beauty and for the terror they may represent to patients suffering from disease. Beauty in this context is a relative term. It may be seen as the delicate lacework of cells within the normal human brain reminiscent of a Jackson Pollack masterpiece, or the multitude of colors and textures formed by fungal organisms in a microbiology lab. Herein lies the juxtaposition image makers seek to represent. When contemplated in isolation, each represents a visually interesting image. However, when viewed with an awareness of the context in which the image was obtained, each image takes on the ability to evoke an alternative human emotion. PMID- 26828554 TI - Global perspectives: clinical imaging in Romania. PMID- 26828555 TI - Email solicitation for scholarly work--a single researcher's perspective. AB - INTRODUCTION: Publishing is important for career progression. The traditional journal model results in subscribers bearing publication costs. The eagerness with which researchers seek journals for the publishing of their work, along with the internet, has resulted in the creation of a new model called open access (OA). Author/s or their institution/s pay an actual publication fee. This has in turn resulted in the creation of questionable journals which charge steep publishing fees. METHODS: Emails soliciting publication to one of the authors (VG) were collected for the month of March 2015. Information collected included costs of OA publishing, and whether or not this information was readily available. The appropriateness of said solicitations was also assessed with regard to topics with which the targeted author was familiar. RESULTS: There was a total of 44 solicitations: 3 were duplicates. Out of 41 solicitations, 20 (49%) were appropriate. The open access fee was readily available in 27 out of 41 solicitations (66%). The open access fee averaged $475, ranging from $25 to $1500. The only journal which provided true OA was Medical Principles and Practice, with no fees charged whatsoever. DISCUSSION: Potential authors should carefully investigate OA journals prior to choosing journals wherein to submit their work. PMID- 26828557 TI - Figure 1: An App Review. PMID- 26828558 TI - PicSafe Medi: a clinical photography app review. AB - Medical photographs are used in many clinical settings; however, there are significant risks associated with using the camera feature on mobile devices, namely, breaches of security. PicSafe Medi is an app that allows healthcare professionals to take clinical photographs using smart devices whilst addressing the concerns of patient confidentiality. We review the app to assess its functionality in a UK clinical setting, taking into account UK guidelines such as those offered by the General Medical Council, UK legislation, the Institute of Medical Illustrators and the Department of Health. PMID- 26828561 TI - External quality assessment studies for laboratory performance of molecular and serological diagnosis of Chikungunya virus infection. AB - BACKGROUND: Since the re-emergence of Chikungunya virus (CHIKV) in Reunion in 2005 and the recent outbreak in the Caribbean islands with an expansion to the Americas the CHIK diagnostic became very important. OBJECTIVES: We evaluate the performance of laboratories regarding molecular and serological diagnostic of CHIK worldwide. STUDY DESIGN: A panel of 12 samples for molecular and 13 samples for serology were provided to 60 laboratories in 40 countries for evaluating the sensitivity and specificity of molecular and serology testing. RESULTS: The panel for molecular diagnostic testing was analysed by 56 laboratories returning 60 data sets of results whereas the 56 and 60 data sets were returned for IgG and IgM diagnostic from the participating laboratories. Twenty-three from 60 data sets performed optimal, 7 acceptable and 30 sets of results require improvement. From 50 data sets only one laboratory shows an optimal performance for IgM detection, followed by 9 data sets with acceptable and the rest need for improvement. From 46 IgG serology data sets 20 provide an optimal, 2 an acceptable and 24 require improvement performance. The evaluation of some of the diagnostic performances allows linking the quality of results to the in-house methods or commercial assays used. CONCLUSION: The external quality assurance for CHIK diagnostics provides a good overview on the laboratory performance regarding sensitivity and specificity for the molecular and serology diagnostic required for the quick and reliable analysis of suspected CHIK patients. Nearly half of the laboratories have to improve their diagnostic profile to achieve a better performance. PMID- 26828562 TI - Transition-Metal Hydride Radical Cations. AB - Transition-metal hydride radical cations (TMHRCs) are involved in a variety of chemical and biochemical reactions, making a more thorough understanding of their properties essential for explaining observed reactivity and for the eventual development of new applications. Generally, these species may be treated as the ones formed by one-electron oxidation of diamagnetic analogues that are neutral or cationic. Despite the importance of TMHRCs, the generally sensitive nature of these complexes has hindered their development. However, over the last four decades, many more TMHRCs have been synthesized, characterized, isolated, or hypothesized as reaction intermediates. This comprehensive review focuses on experimental studies of TMHRCs reported through the year 2014, with an emphasis on isolated and observed species. The methods used for the generation or synthesis of TMHRCs are surveyed, followed by a discussion about the stability of these complexes. The fundamental properties of TMHRCs, especially those pertaining to the M-H bond, are described, followed by a detailed treatment of decomposition pathways. Finally, reactions involving TMHRCs as intermediates are described. PMID- 26828563 TI - Development and validation of a prognostic model for recurrent glioblastoma patients treated with bevacizumab and irinotecan. AB - BACKGROUND: Predictive markers and prognostic models are required in order to individualize treatment of recurrent glioblastoma (GBM) patients. Here, we sought to identify clinical factors able to predict response and survival in recurrent GBM patients treated with bevacizumab (BEV) and irinotecan. MATERIAL AND METHODS: A total of 219 recurrent GBM patients treated with BEV plus irinotecan according to a previously published treatment protocol were included in the initial population. Prognostic models were generated by means of multivariate logistic and Cox regression analysis. RESULTS: In multivariate analysis, corticosteroid use had a negative predictive impact on response at first evaluation (OR 0.45; 95% CI 0.22-0.93; p = 0.03) and at best response (OR 0.51; 95% CI 0.26-1.02; p = 0.056). Three significant (p < 0.05) prognostic factors associated with reduced progression-free survival and overall survival (OS) were identified. These factors were included in the final model for OS, namely corticosteroid use (HR 1.70; 95% CI 1.18-2.45; p = 0.004), neurocognitive deficit (HR 1.40; 95% CI 1.04 1.89; p = 0.03) and multifocal disease (HR 1.56; 95% CI 1.15-2.11; p < 0.0001). Based on these results a prognostic index able to calculate the probability for OS at 6 and 12 months for the individual patient was established. The predictive value of the model for OS was validated in a separate patient cohort of 85 patients. DISCUSSION AND CONCLUSION: A prognostic model for OS was established and validated. This model can be used by physicians to risk stratify the individual patient and together with the patient decide whether to initiate BEV relapse treatment. PMID- 26828564 TI - ICU versus Non-ICU Hospital Death: Family Member Complicated Grief, Posttraumatic Stress, and Depressive Symptoms. AB - BACKGROUND: Family members of patients who die in an ICU are at increased risk of psychological sequelae compared to those who experience a death in hospice. OBJECTIVE: This study explored differences in rates and levels of complicated grief (CG), posttraumatic stress disorder (PTSD), and depression between family members of patients who died in an ICU versus a non-ICU hospital setting. Differences in family members' most distressing experiences at the patient's end of life were also explored. METHODS: The study was an observational cohort. Subjects were next of kin of 121 patients who died at a large, Midwestern academic hospital; 77 died in the ICU. Family members completed measures of CG, PTSD, depression, and end-of-life experiences. RESULTS: Participants were primarily Caucasian (93%, N = 111), female (81%, N = 98), spouses (60%, N = 73) of the decedent, and were an average of nine months post-bereavement. Forty percent of family members met the Inventory of Complicated Grief CG cut-off, 31% met the Impact of Events Scale-Revised PTSD cut-off, and 51% met the Center for Epidemiologic Studies Depression Scale depression cut-off. There were no significant differences in rates or levels of CG, PTSD, or depressive symptoms reported by family members between hospital settings. Several distressing experiences were ranked highly by both groups, but each setting presented unique distressing experiences for family members. CONCLUSIONS: Psychological distress of family members did not differ by hospital setting, but the most distressing experiences encountered at end of life in each setting highlight potentially unique interventions to reduce distress post-bereavement for family members. PMID- 26828565 TI - Optimized Cryopreservation and Banking of Human Bone-Marrow Fragments and Stem Cells. AB - Adult mesenchymal stem cells are a promising source for cell therapies and tissue engineering applications. Current procedures for banking of human bone-marrow mesenchymal stem cells (hBM-MSCs) require cell isolation and expansion, and thus the use of large amounts of animal sera. However, animal-derived culture supplements have the potential to trigger infections and severe immune reactions. The aim of this study was to investigate an optimized method for cryopreservation of human bone-marrow fragments for application in cell banking procedures where stem-cell expansion and use are not immediately needed. Whole trabecular fragments enclosing the bone marrow were stored in liquid nitrogen for 1 year in a cryoprotective solution containing a low concentration of dimethyl sulfoxide and a high concentration of human serum (HuS). After thawing, the isolation, colony-forming-unit ability, proliferation, morphology, stemness-related marker expression, cell senescence, apoptosis, and multi-lineage differentiation potential of hBM-MSCs were tested in media containing HuS compared with hBM-MSCs isolated from fresh fragments. Human BM-MSCs isolated from cryopreserved fragments expressed MSC markers until later passages, had a good proliferation rate, and exhibited the capacity to differentiate toward osteogenic, adipogenic, and myogenic lineages similar to hBM-MSCs isolated from fresh fragments. Moreover, the cryopreservation method did not induce cell senescence or cell death. These results imply that minimal processing may be adequate for the banking of tissue samples with no requirement for the immediate isolation and use of hBM-MSCs, thus limiting cost and the risk of contamination, and facilitating banking for clinical use. Furthermore, the use of HuS for cryopreservation and expansion/differentiation has the potential for clinical application in compliance with good manufacturing practice standards. PMID- 26828566 TI - Pancreaticopleural Fistula. PMID- 26828568 TI - A systematic review on heart rate variability in Bulimia Nervosa. AB - Eating disorders are associated with alterations of the autonomic nervous system (ANS). Among other indices, heart rate variability (HRV) provides a readily available index of ANS function. While ANS dysfunction indexed by HRV in Anorexia Nervosa has been addressed in previous reviews, here we aimed to review the current evidence on HRV in Bulimia Nervosa (BN). A systematic literature search in Web of Science, PsycInfo, Scopus, and PubMed identified 17 studies reporting HRV in patients with BN. Studies described (i) differences in resting state HRV in patients compared to controls, (ii) alterations in the stress response in BN indexed by HRV, and (iii) treatment effects on HRV in patients with BN. Despite a number of conflicting results, we conclude that BN is characterized by increased resting state vagally-mediated HRV and an impaired stress-response. Intervention studies suggest that altered ANS-activity in BN is at least partially reversible. Future studies on the complex relation between BN and HRV should investigate the effect of comorbid disorders, subtypes of BN, and mechanisms affecting treatment outcome. PMID- 26828567 TI - Structural characterisation of human galectin-4 N-terminal carbohydrate recognition domain in complex with glycerol, lactose, 3'-sulfo-lactose, and 2' fucosyllactose. AB - Galectin-4 is a tandem-repeat galectin with two distinct carbohydrate recognition domains (CRD). Galectin-4 is expressed mainly in the alimentary tract and is proposed to function as a lipid raft and adherens junction stabilizer by its glycan cross-linking capacity. Galectin-4 plays divergent roles in cancer and inflammatory conditions, either promoting or inhibiting each disease progression, depending on the specific pathological condition. The study of galectin-4's ligand-binding profile may help decipher its roles under specific conditions. Here we present the X-ray structures of human galectin-4 N-terminal CRD (galectin 4N) bound to different saccharide ligands. Galectin-4's overall fold and its core interactions to lactose are similar to other galectin CRDs. Galectin-4N recognises the sulfate cap of 3'-sulfated glycans by a weak interaction through Arg45 and two water-mediated hydrogen bonds via Trp84 and Asn49. When galectin-4N interacts with the H-antigen mimic, 2'-fucosyllactose, an interaction is formed between the ring oxygen of fucose and Arg45. The extended binding site of galectin-4N may not be well suited to the A/B-antigen determinants, alpha GalNAc/alpha-Gal, specifically due to clashes with residue Phe47. Overall, galectin-4N favours sulfated glycans whilst galectin-4C prefers blood group determinants. However, the two CRDs of galectin-4 can, to a less extent, recognise each other's ligands. PMID- 26828569 TI - Transcranial electrical stimulation during sleep enhances declarative (but not procedural) memory consolidation: Evidence from a meta-analysis. AB - This meta-analysis summarizes research examining whether transcranial electrical stimulation (transcranial direct current stimulation with oscillating and constant currents; transcranial alternating current stimulation), administered during sleep, can modulate declarative and procedural memory consolidation. Included in the meta-analysis were 13 experiments that represented data from 179 participants. Study findings were summarized using standardized mean difference (SMD) which is an effect size that summarizes differences in standard deviation units. Results showed electrical stimulation during sleep could enhance (SMD=0.447; p=.003) or disrupt (SMD=-0.476, p=.030) declarative memory consolidation. However, transcranial electric stimulation does not appear to be able to enhance (SMD=0.154, p=.279) or disrupt (SMD=0.076, p=.675) procedural memory consolidation. This meta-analysis provides strong evidence that TES is able to modulate some consolidation processes. Additional research is required to determine the mechanisms by which transcranial electrical stimulation is able to influence declarative memory consolidation. Finally, it is yet to be determined whether transcranial electrical stimulation can modulate procedural memory consolidation. PMID- 26828570 TI - Unsymmetrical Aryl(2,4,6-trimethoxyphenyl)iodonium Salts: One-Pot Synthesis, Scope, Stability, and Synthetic Studies. AB - Diaryliodonium salts have recently attracted significant attention as metal-free arylation reagents in organic synthesis, and efficient access to these salts is critical for advancement of their use in reaction discovery and development. The trimethoxybenzene-derived auxiliary is a promising component of unsymmetrical variants, yet access remains limited. Here, a one-pot synthesis of aryl(2,4,6 trimethoxyphenyl)iodonium salts from aryl iodides, m-CPBA, p-toluenesulfonic acid, and trimethoxybenzene is described. Optimization of the reaction conditions for this one-pot synthesis was enabled by the method of multivariate analysis. The reaction is fast (<1 h), provides a high yield of product (>85% average), and has broad substrate scope (>25 examples) including elaborate aryl iodides. The utility of these reagents is demonstrated in moderate to high yielding arylation reactions with C-, N-, O-, and S-nucleophiles including the synthesis of a liquid crystal molecule. PMID- 26828572 TI - Synthesis of Sodium Complexes Supported with NNO-Tridentate Schiff Base Ligands and Their Applications in the Ring-Opening Polymerization of L-Lactide. AB - A series of sodium complexes bearing NNO-tridentate Schiff base ligands with an N pendant arm were synthesized and used as catalysts for the ring-opening polymerization of L-lactide (L-LA). Electronic effects of ancillary ligands coordinated by sodium complexes substantially influence the catalysis, and ligands with electron-donating groups increase the catalytic activity of the sodium complexes for catalyzing L-LA polymerization. In particular, a sodium complex bearing a 4-methoxy group has the highest activity with conversion up to 95% within 30 s at 0 degrees C and a low polydispersity index of 1.13, whereas the 4-bromo group showed the poorest performance with regard to the catalytic rate of L-LA polymerization in the presence of benzyl alcohol (BnOH). (1)H NMR pulsed-gradient spin-echo diffusion experiments and single-crystal X-ray analyses showed that sodium complexes [L(H)Na(THF)]2 and [L(4-Cl)Na(THF)]2 were dinuclear species in both solution and the solid state. The kinetic results indicated a first-order dependence on each of [[L(4-Cl)Na]2], [l-LA], and [BnOH]. PMID- 26828571 TI - Cognitive Training and Work Therapy for the Treatment of Verbal Learning and Memory Deficits in Veterans With Alcohol Use Disorders. AB - OBJECTIVE: This study focused on the efficacy of cognitive training for verbal learning and memory deficits in a population of older veterans with alcohol use disorders. METHODS: Veterans with alcohol use disorders, who were in outpatient treatment at VA facilities and in early-phase recovery (N = 31), were randomized to receive a three-month trial of daily cognitive training plus work therapy (n = 15) or work therapy alone (n = 16), along with treatment as usual. Participants completed assessments at baseline and at three- and six-month follow-ups; the Hopkins Verbal Learning Task (HVLT) was the primary outcome measure. RESULTS: Participants were primarily male (97%) and in their mid-50s (M = 55.16, SD = 5.16) and had been sober for 1.64 (SD = 2.81) months. Study retention was excellent (91% at three-month follow-up) and adherence to treatment in both conditions was very good. On average, participants in the cognitive training condition had more than 41 hours of cognitive training, and both conditions had more than 230 hours of productive activity. HVLT results at three-month follow-up revealed significant condition effects favoring cognitive training for verbal learning (HVLT Trial-3 T-score, p < .005, Cohen's d = 1.3) and verbal memory (HVLT Total T-score, p < .01, Cohen's d = 1.1). Condition effects were sustained at six-month follow-up. At baseline, 55.9% of participants showed a significant deficit in verbal memory and 58.8% showed a deficit in verbal learning compared with a premorbid estimate of verbal IQ. At three-month follow-up there was a significant reduction in the number of participants in the cognitive training condition with clinically significant verbal memory deficits (p < .01, number needed to treat = 3.0) compared with the work therapy alone condition and a trend toward significance for verbal learning deficits, which was not sustained at six month follow-up. CONCLUSIONS: This National Institute on Drug Abuse-funded pilot study demonstrates that cognitive training within the context of another activating intervention (work therapy) may have efficacy in remediating verbal learning and memory deficits in patients with alcohol use disorder. Findings indicate a large effect for cognitive training in this pilot study, which suggests that further research is warranted. This study is registered on ClinicalTrials.gov (NCT 01410110). PMID- 26828573 TI - Taming Self-Organization Dynamics to Dramatically Control Porous Architectures. AB - We demonstrate templating of functional materials with unexpected and intricate micro- and nanostructures by controlling the condensation, packing, and evaporation of water droplets on a polymer solution. Spontaneous evaporation of a polymer solution induces cooling of the liquid surface and water microdroplet condensation from the ambient vapor. These droplets pack together and act as a template to imprint an entangled polymer film. This breath figure (BF) phenomenon is an example of self-organization that involves the long-range ordering of droplets. Equilibrium-based analysis provides many insights into contact angles and drop stability of individual drops, but the BF phenomenon remains poorly understood thus far, preventing translation to real applications. Here we investigate the dynamics of this phenomenon to separate out the competing influences and then introduce a modulation scheme to ultimately manipulate the water vapor-liquid equilibrium independently from the solvent evaporation. This approach to BF control provides insights into the mechanism, a rationale for microstructure design, and evidence for the benefits of dynamical control of self organization systems. We finally present dramatically different porous architectures from this approach reminiscent of microscale Petri dishes, conical flasks, and test tubes. PMID- 26828574 TI - Gas-Microjet Reactive Scattering: Collisions of HCl and DCl with Cool Salty Water. AB - Liquid microjets provide a powerful means to investigate reactions of gases with salty water in vacuum while minimizing gas-vapor collisions. We use this technique to explore the fate of gaseous HCl and DCl molecules impinging on 8 molal LiCl and LiBr solutions at 238 K. The experiments reveal that HCl or DCl evaporate infrequently if they become thermally accommodated at the surface of either solution. In particular, we observe minimal thermal desorption of HCl following HCl collisions and no distinct evidence for rapid, interfacial DCl->HCl exchange following DCl collisions. These results imply that surface thermal motions are not generally strong enough to propel momentarily trapped HCl or DCl back into the gas phase before they ionize and disappear into solution. Instead, only HCl and DCl molecules that scatter directly from the surface escape entry. These recoiling molecules transfer less energy upon collision to LiBr/H2O than to LiCl/H2O, reflecting the heavier mass of Br(-) than of Cl(-) in the interfacial region. PMID- 26828575 TI - Interaction of peptides with cell membranes: insights from molecular modeling. AB - The investigation of the interaction of peptides with cell membranes is the focus of active research. It can enhance the understanding of basic membrane functions such as membrane transport, fusion, and signaling processes, and it may shed light on potential applications of peptides in biomedicine. In this review, we will present current advances in computational studies on the interaction of different types of peptides with the cell membrane. Depending on the properties of the peptide, membrane, and external environment, the peptide-membrane interaction shows a variety of different forms. Here, on the basis of recent computational progress, we will discuss how different peptides could initiate membrane pores, translocate across the membrane, induce membrane endocytosis, produce membrane curvature, form fibrils on the membrane surface, as well as interact with functional membrane proteins. Finally, we will present a conclusion summarizing recent progress and providing some specific insights into future developments in this field. PMID- 26828577 TI - State Variation in Preventive Care Visits, by Patient Characteristics, 2012. AB - KEY FINDINGS: Data from the National Ambulatory Medical Care Survey, 2012. In 2012, 61.4 preventive care visits were made to office-based physicians per 100 persons. The female rate (76.6 visits per 100 females) exceeded the male rate (45.4 visits per 100 males) by 69%. Among the 34 most populous states, the rate of preventive care visits exceeded the national rate in 1 state (Connecticut) and was lower than the national rate in 11 states (Arkansas, Indiana, Iowa, Michigan, Missouri, North Carolina, Oklahoma, Oregon, Pennsylvania, South Carolina, and Washington). The rate of preventive care visits to primary care physicians in the 34 most populous states exceeded the national rate in 1 state (Connecticut) and was lower than the national rate in 7 states (Arkansas, Indiana, Iowa, Missouri, North Carolina, Pennsylvania, and Washington). PMID- 26828576 TI - Visible Light Photoredox Cross-Coupling of Acyl Chlorides with Potassium Alkoxymethyltrifluoroborates: Synthesis of alpha-Alkoxyketones. AB - A visible-light, single-electron-transfer (SET), photoredox cross-coupling for the synthesis of alpha-alkoxyketones has been developed. In this method, various aliphatic and aromatic acyl chlorides were successfully coupled with structurally diverse potassium alkoxymethyltrifluoroborates, producing the corresponding alpha alkoxyketones with high yields. In this operationally simple and mild cross coupling protocol, the desired ketones are obtained in one step from bench stable starting materials by a bond connection that is unique to both alkylboron chemistry and photoredox/Ni catalysis. PMID- 26828578 TI - Pathway to Best Practice in Spirometry in the Ambulatory Setting. AB - Spirometry performed in the ambulatory setting is an invaluable tool for diagnosis, monitoring, and evaluation of respiratory health in patients with chronic lung disease. If spirometry is not performed according to American Thoracic Society (ATS) guidelines, unnecessary repeated testing, increased expenditure of time and money, and increased patient and family anxiety may result. Two respiratory therapists at Mission Health System in Asheville, NC, identified an increase in patients arriving at the pulmonary function testing (PFT) laboratories with abnormal spirometry results obtained in the ambulatory setting. These abnormal results were due to incorrect testing procedure, not chronic lung disease. Three training methods were developed to increase knowledge of correct spirometry testing procedure in the ambulatory setting. The therapists also created a plan to educate offices that do not perform spirometry on the importance and availability of PFT services at our hospital for the population of patients with chronic lung disease. Notable improvements in posttraining test results were demonstrated. The education process was evaluated by a leading respiratory expert, with improvements suggested and implemented. Next steps are listed. PMID- 26828579 TI - Parenteral nutrition in the ICU setting: need for a shift in utilization. AB - PURPOSE OF REVIEW: The difficulties to feed the patients adequately with enteral nutrition alone have drawn the attention of the clinicians toward the use of parenteral nutrition, although recommendations by the recent guidelines are conflicting. This review focuses on the intrinsic role of parenteral nutrition, its new indication, and modalities of use for the critically ill patients. RECENT FINDINGS: A recent trial demonstrated that selecting either parenteral nutrition or enteral nutrition for early nutrition has no impact on clinical outcomes. However, it must be acknowledged that the risk of relative overfeeding is greater when using parenteral nutrition and the risk of underfeeding is greater when using enteral nutrition because of gastrointestinal intolerance. Both overfeeding and underfeeding in the critically ill patients are associated with deleterious outcomes. Thus, early and adequate feeding according to the specific energy needs can be recommended as the optimal feeding strategy. SUMMARY: Parenteral nutrition can be used to substitute or supplement enteral nutrition, if adequately prescribed. Testing for enteral nutrition tolerance during 2-3 days after ICU admission provides the perfect timing to start parenteral nutrition, if needed. In case of absolute contraindication for enteral nutrition, consider starting parenteral nutrition carefully to avoid overfeeding. PMID- 26828580 TI - Lipid metabolism in critical illness. AB - PURPOSE OF REVIEW: This article describes recent findings regarding lipid metabolism in critical illness as well as in lipid therapy. RECENT FINDINGS: In critical illness, in the presence of a decrease in lipid absorption, adipose tissue lipolysis raises triglyceride levels. High-density lipoprotein and low density lipoprotein are decreased because of impairment of lecithin-cholesterol acyltransferase, mainly in sepsis. In septic patients, lipid profile may be a predictor of survival. Nonsurvivors have lower levels of high-density lipoprotein and low-density lipoprotein. In metabolomic studies, most of the changes from baseline in septic patients were related to lipid metabolism. Lysophosphatidylcholine was also significantly lower in nonsurviving septic patients. SUMMARY: Lipid profile results are too often neglected by the clinician despite increasing knowledge in the modifications related to septic state as well as the importance of these values in the prognosis of the critically ill. Lipid administration (enterally or parenterally) should be guided by better knowledge of the lipid metabolism of the patient. PMID- 26828582 TI - Optimal nutrition in the paediatric ICU. AB - PURPOSE OF REVIEW: This article describes the current best available evidence on optimal nutrition in the paediatric intensive care based on different levels of outcome, which can be divided in surrogate and hard clinical outcome parameters. RECENT FINDINGS: Undernutrition is associated with increased morbidity and mortality, whereas in specific cohorts of critically ill children, such as those with burn injury, obesity is associated with more complications, longer length of stay, and decreased likelihood of survival. There is a relation with adequacy of delivery of enteral nutrition and the amount of protein on length of hospital stay, neurological status, and mortality. Studies relating organ function, other than skin healing after thermal injury, with the nutritional status are scarce. There is also a scarcity of data concerning long-term follow-up and health economics. SUMMARY: Until now, there are no randomized controlled trials which have investigated a causal relation between different feeding regimens on the nutritional status and short and long-term outcome. As a result current optimal nutritional strategies are based on small trials with surrogate outcome parameters. Prospective randomized studies are needed with nutritional and/or metabolic interventions to come to an optimal feeding strategy for critically ill children. PMID- 26828581 TI - Desaturase and elongase-limiting endogenous long-chain polyunsaturated fatty acid biosynthesis. AB - PURPOSE OF REVIEW: Endogenous synthesis of the long-chain polyunsaturated fatty acids (LCPUFAs) is mediated by the fatty acid desaturase (FADS) gene cluster (11q12-13.1) and elongation of very long-chain fatty acids 2 (ELOVL2) (6p24.2) and ELOVL5 (6p12.1). Although older biochemical work identified the product of one gene, FADS2, rate limiting for LCPUFA synthesis, recent studies suggest that polymorphisms in any of these genes can limit accumulation of product LCPUFA. RECENT FINDINGS: Genome-wide association study (GWAS) of Greenland Inuit shows strong adaptation signals within FADS gene cluster, attributed to high omega-3 fatty acid intake, while GWAS found ELOVL2 associated with sleep duration, age and DNA methylation. ELOVL5 coding mutations cause spinocerebellar ataxia 38, and epigenetic marks were associated with depression and suicide risk. Two sterol response element binding sites were found on ELOVL5, a SREBP-1c target gene. Minor allele carriers of a 3 single nucleotide polymorphism (SNP) haplotype in ELOVL2 have decreased 22 : 6n-3 levels. Unequivocal molecular evidence shows mammalian FADS2 catalyzes direct Delta4-desaturation to yield 22 : 6n-3 and 22 : 5n-6. An SNP near FADS1 influences the levels of 5-lipoxygenase products and epigenetic alteration. SUMMARY: Genetic polymorphisms within FADS and ELOVL can limit LCPUFA product accumulation at any step of the biosynthetic pathway. PMID- 26828583 TI - Does feeding induce maximal stimulation of protein balance? AB - PURPOSE OF REVIEW: Muscle wasting is dramatic in critically ill patients and related to worsened outcome. The question is whether this can be prevented or reduced by adequate protein feeding. Recommendations for protein requirements are different between different societies, because of limited and weak evidence. Most studies, on which these recommendations are based, use nitrogen balance as primary outcome. However, nitrogen balance to estimate protein needs over short periods, is not reliable. RECENT FINDINGS: Studies using tracer methodology to assess the effects of feeding on whole-body protein synthesis, breakdown and balance, show that both adult and pediatric critically ill patients can utilize parenterally and enterally given proteins or amino acids to build body protein, and that the extra amino acids are not oxidized. SUMMARY: Recent studies show a positive correlation between protein intake and protein balance, with many patients reaching a positive protein balance. However, many questions remain. Especially whether adult patients should have a constant positive protein balance, whether the route of administration affects utilization, which proteins are synthesized and whether these are beneficial, is more protein better and what is the upper limit, and whether a positive protein balance affects clinical outcome? PMID- 26828584 TI - Indications and contraindications for infusing specific amino acids (leucine, glutamine, arginine, citrulline, and taurine) in critical illness. AB - PURPOSE OF REVIEW: The review assesses the utility of supplementing parenteral or enteral nutrition of ICU patients with each of five specific amino acids that display pharmacological properties. Specifying indications implies also stating contraindications.Combined supplementation of amino acids with omega3-fatty acids and/or trace elements (immune-enhancing diets) will not be considered in this review because these mixtures do not allow the role of amino acids in the effect (positive or negative) of the mixture to be isolated, and so cannot show whether or not supplementation of a given amino acid is indicated. RECENT FINDINGS: After decades of unbridled use of glutamine (GLN) supplementation in critically ill patients, recent large trials have brought a note of caution, indicating for example that GLN should not be used in patients with multiple organ failure. Yet these large trials do not change the conclusions of recent meta-analyses. Arginine (ARG), as a single dietary supplement, is probably not harmful in critical illness, in particular in a situation of ARG deficiency syndrome with low nitric oxide production. Citrulline supplementation strongly improves microcirculation in animal models with gut injury, but clinical studies are lacking. Taurine has a potent protective effect against ischemic reperfusion injury. SUMMARY: Amino acid-based pharmaconutrition has displayed familiar 'big project' stages: enthusiasm (citrulline and taurine), doubt (GLN), hunt for the guilty (ARG), and backpedalling (leucine). Progress in this field is very slow, and sometimes gives way to retreat, as demonstrated by recent large trials on GLN supplementation. PMID- 26828585 TI - Does the use of specialized proresolving molecules in critical care offer a more focused approach to controlling inflammation than that of fish oils? AB - PURPOSE OF REVIEW: The literature regarding the use of fish oils in the critically ill to limit the inflammatory and catabolic response have been inconsistent. The objective of this manuscript is to review a newly discovered class of specialized proresolving molecules (SPMs), which could help elucidate the discrepancies reported in the critical care literature regarding the anti inflammatory benefits of fish oil/omega-3 fatty acids. RECENT FINDINGS: Although use of fish oil has traditionally been thought to reduce or limit the inflammatory process in the critical ill, a new class of endogenously produced highly active lipid mediators derived from arachidonic acid and omega-3 fatty acids (lipoxins, resolvins, protectins, and maresins) have been shown to actively enhance resolution of inflammation. These SPMs stimulate the cardinal signs of resolution of inflammation, which include the cessation of leukocytic infiltration, a countering of the effects of proinflammatory mediators, stimulation of the uptake of apoptotic neutrophils, promotion of the clearance of necrotic cellular debris, and enhancement of the host's ability to eliminate microbial invasion. SUMMARY: By actively turning off inflammation (instead of simply attenuating its natural course), SPMs have shown more consistent effects in decreasing pain and risk of sepsis, increasing epithelialization and wound healing, promoting tissue regeneration, potentiating the effects of antibiotics, and enhancing adaptive immunity. PMID- 26828586 TI - Peripheral Primitive Neuroectodermal Tumor and Neurofibromatosis Type 1 in an Adolescent Male. PMID- 26828587 TI - Treatment of fecal retention is important in the management of overactive bladder in children. AB - AIMS: The investigation of fecal retention using objective and patient-friendly tools, rather than the diagnosis of constipation, might be important in the management of overactive bladder (OAB) in children. The present study aimed to evaluate the incidence and grade of fecal retention in children with OAB and to determine the effectiveness of laxative treatment for fecal retention in the management of OAB in children. METHODS: This study included 88 children with OAB aged 5-15 years. Fecal retention was defined as type 1/2 feces (Bristol stool form scale) or a Leech score above eight points, and constipation was determined according to the ROME III criteria. Among the 88 children, 71 with fecal retention or constipation were treated with oral laxatives (polyethylene glycol 3,350/4,000 or lactulose) for 2 weeks, and the responses to the treatment were assessed. RESULTS: Among the 88 children, 63 (71.6%) had a Leech score above eight points as assessed by plain abdominal radiography, 52 (59.1%) had type 1/2 feces (Bristol stool form scale), 24 (27.3%) had functional constipation and only 6 (6.8%) had none of either. Among the 71 children who received laxative treatment for 2 weeks, 58 (81.7%) reported an improvement in OAB symptoms. Additionally, the number of children with a Leech score above eight points was significantly higher in the good response group than in the poor response group (P = 0.014). CONCLUSION: Investigation of fecal retention with the Leech scoring system and laxative treatment might be helpful in the management of OAB in children. Neurourol. Urodynam. 36:490-494, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26828588 TI - Recommendations for a step-wise comparative approach to the evaluation of new screening tests for colorectal cancer. AB - BACKGROUND: New screening tests for colorectal cancer continue to emerge, but the evidence needed to justify their adoption in screening programs remains uncertain. METHODS: A review of the literature and a consensus approach by experts was undertaken to provide practical guidance on how to compare new screening tests with proven screening tests. RESULTS: Findings and recommendations from the review included the following: Adoption of a new screening test requires evidence of effectiveness relative to a proven comparator test. Clinical accuracy supported by programmatic population evaluation in the screening context on an intention-to-screen basis, including acceptability, is essential. Cancer-specific mortality is not essential as an endpoint provided that the mortality benefit of the comparator has been demonstrated and that the biologic basis of detection is similar. Effectiveness of the guaiac-based fecal occult blood test provides the minimum standard to be achieved by a new test. A 4 phase evaluation is recommended. An initial retrospective evaluation in cancer cases and controls (Phase 1) is followed by a prospective evaluation of performance across the continuum of neoplastic lesions (Phase 2). Phase 3 follows the demonstration of adequate accuracy in these 2 prescreening phases and addresses programmatic outcomes at 1 screening round on an intention-to-screen basis. Phase 4 involves more comprehensive evaluation of ongoing screening over multiple rounds. Key information is provided from the following parameters: the test positivity rate in a screening population, the true-positive and false positive rates, and the number needed to colonoscope to detect a target lesion. CONCLUSIONS: New screening tests can be evaluated efficiently by this stepwise comparative approach. PMID- 26828589 TI - Osteogenic Differentiation of MSC through Calcium Signaling Activation: Transcriptomics and Functional Analysis. AB - The culture of progenitor mesenchymal stem cells (MSC) onto osteoconductive materials to induce a proper osteogenic differentiation and mineralized matrix regeneration represents a promising and widely diffused experimental approach for tissue-engineering (TE) applications in orthopaedics. Among modern biomaterials, calcium phosphates represent the best bone substitutes, due to their chemical features emulating the mineral phase of bone tissue. Although many studies on stem cells differentiation mechanisms have been performed involving calcium-based scaffolds, results often focus on highlighting production of in vitro bone matrix markers and in vivo tissue ingrowth, while information related to the biomolecular mechanisms involved in the early cellular calcium-mediated differentiation is not well elucidated yet. Genetic programs for osteogenesis have been just partially deciphered, and the description of the different molecules and pathways operative in these differentiations is far from complete, as well as the activity of calcium in this process. The present work aims to shed light on the involvement of extracellular calcium in MSC differentiation: a better understanding of the early stage osteogenic differentiation program of MSC seeded on calcium-based biomaterials is required in order to develop optimal strategies to promote osteogenesis through the use of new generation osteoconductive scaffolds. A wide spectrum of analysis has been performed on time dependent series: gene expression profiles are obtained from samples (MSC seeded on calcium-based scaffolds), together with related microRNAs expression and in vivo functional validation. On this basis, and relying on literature knowledge, hypotheses are made on the biomolecular players activated by the biomaterial calcium-phosphate component. Interestingly, a key role of miR-138 was highlighted, whose inhibition markedly increases osteogenic differentiation in vitro and enhance ectopic bone formation in vivo. Moreover, there is evidence that Ca-P substrate triggers osteogenic differentiation through genes (SMAD and RAS family) that are typically regulated during dexamethasone (DEX) induced differentiation. PMID- 26828590 TI - BteA Secreted from the Bordetella bronchiseptica Type III Secetion System Induces Necrosis through an Actin Cytoskeleton Signaling Pathway and Inhibits Phagocytosis by Macrophages. AB - BteA is one of the effectors secreted from the Bordetella bronchiseptica type III secretion system. It has been reported that BteA induces necrosis in mammalian cells; however, the roles of BteA during the infection process are largely unknown. In order to investigate the BteA functions, morphological changes of the cells infected with the wild-type B. bronchiseptica were examined by time-lapse microscopy. L2 cells, a rat lung epithelial cell line, spread at 1.6 hours after B. bronchiseptica infection. Membrane ruffles were observed at peripheral parts of infected cells during the cell spreading. BteA-dependent cytotoxicity and cell detachment were inhibited by addition of cytochalasin D, an actin polymerization inhibitor. Domain analyses of BteA suggested that two separate amino acid regions, 200-312 and 400-658, were required for the necrosis induction. In order to examine the intra/intermolecular interactions of BteA, the amino- and the carboxyl-terminal moieties were purified as recombinant proteins from Escherichia coli. The amino-terminal moiety of BteA appeared to interact with the carboxyl terminal moiety in the pull-down assay in vitro. When we measured the amounts of bacteria phagocytosed by J774A.1, a macrophage-like cell line, the phagocytosed amounts of B. bronchiseptica strains that deliver BteA into the host cell cytoplasm were significantly lower than those of strains that lost the ability to translocate BteA into the host cell cytoplasm. These results suggest that B. bronchiseptica induce necrosis by exploiting the actin polymerization signaling pathway and inhibit macrophage phagocytosis. PMID- 26828591 TI - PSAMM: A Portable System for the Analysis of Metabolic Models. AB - The genome-scale models of metabolic networks have been broadly applied in phenotype prediction, evolutionary reconstruction, community functional analysis, and metabolic engineering. Despite the development of tools that support individual steps along the modeling procedure, it is still difficult to associate mathematical simulation results with the annotation and biological interpretation of metabolic models. In order to solve this problem, here we developed a Portable System for the Analysis of Metabolic Models (PSAMM), a new open-source software package that supports the integration of heterogeneous metadata in model annotations and provides a user-friendly interface for the analysis of metabolic models. PSAMM is independent of paid software environments like MATLAB, and all its dependencies are freely available for academic users. Compared to existing tools, PSAMM significantly reduced the running time of constraint-based analysis and enabled flexible settings of simulation parameters using simple one-line commands. The integration of heterogeneous, model-specific annotation information in PSAMM is achieved with a novel format of YAML-based model representation, which has several advantages, such as providing a modular organization of model components and simulation settings, enabling model version tracking, and permitting the integration of multiple simulation problems. PSAMM also includes a number of quality checking procedures to examine stoichiometric balance and to identify blocked reactions. Applying PSAMM to 57 models collected from current literature, we demonstrated how the software can be used for managing and simulating metabolic models. We identified a number of common inconsistencies in existing models and constructed an updated model repository to document the resolution of these inconsistencies. PMID- 26828592 TI - Melanoma Expressed-CD70 Is Regulated by RhoA and MAPK Pathways without Affecting Vemurafenib Treatment Activity. AB - CD70 is a costimulatory molecule member of the Tumor Necrosis Factor family that is expressed on activated immune cells. Its ectopic expression has been described in several types of cancer cells including lymphomas, renal cell carcinomas and glioblastomas. We have recently described its expression in a part of tumor cells from the vast majority of melanoma biopsies and human melanoma cell lines, and found that CD70 expression decreased over time as the disease progressed. Here, we show that RhoA, BRAF and Mitogen Activating Protein Kinase pathways are involved in the positive transcriptional regulation of CD70 expression in melanomas. Interestingly, the clinical inhibitor of the common BRAF V600E/D variants, Vemurafenib (PLX-4032), which is currently used to treat melanoma patients with BRAF V600E/D-mutated metastatic melanomas, decreased CD70 expression in human CD70+ melanoma cell lines. This decrease was seen in melanoma cells both with and without the BRAFV600E/D mutation, although was less efficient in those lacking the mutation. But interestingly, by silencing CD70 in CD70+ melanoma cell lines we show that PLX-4032-induced melanoma cell killing and its inhibitory effect on MAPK pathway activation are unaffected by CD70 expression. Consequently, our work demonstrates that CD70 ectopic expression in melanomas is not a valuable biomarker to predict tumor cells sensitivity to BRAF V600 inhibitors. PMID- 26828593 TI - The Fdb3 transcription factor of the Fusarium Detoxification of Benzoxazolinone gene cluster is required for MBOA but not BOA degradation in Fusarium pseudograminearum. AB - A number of cereals produce the benzoxazolinone class of phytoalexins. Fusarium species pathogenic towards these hosts can typically degrade these compounds via an aminophenol intermediate, and the ability to do so is encoded by a group of genes found in the Fusarium Detoxification of Benzoxazolinone (FDB) cluster. A zinc finger transcription factor encoded by one of the FDB cluster genes (FDB3) has been proposed to regulate the expression of other genes in the cluster and hence is potentially involved in benzoxazolinone degradation. Herein we show that Fdb3 is essential for the ability of Fusarium pseudograminearum to efficiently detoxify the predominant wheat benzoxazolinone, 6-methoxy-benzoxazolin-2-one (MBOA), but not benzoxazoline-2-one (BOA). Furthermore, additional genes thought to be part of the FDB gene cluster, based upon transcriptional response to benzoxazolinones, are regulated by Fdb3. However, deletion mutants for these latter genes remain capable of benzoxazolinone degradation, suggesting that they are not essential for this process. PMID- 26828595 TI - Elevated Serum Concentration of Chitinase 3-Like 1 is an Independent Prognostic Biomarker for Poor Survival in Lung Cancer Patients. AB - BACKGROUND/AIMS: The chitinase 3-like 1 (CHI3L1) has an important role in cancer progression, and high CHI3L1 expression is associated with the development and progression of cancers. Previous studies had been controversial with respect to the association between CHI3L1 expression and lung cancer prognosis. Thus, we performed a meta-analysis to investigate the prognostic value of CHI3L1 expression in lung cancer. METHODS: We searched Pubmed, Embase, and Wanfang databases to identify eligible studies. Overall survival and disease free survival were collected from included studies. Pooled hazard ratios (HRs) with 95% confidence interval (95%CI) were calculated to estimate the association. Seven studies comprising 911 lung cancer patients were included in this meta analysis. RESULTS: The results showed high CHI3L1 expression was independently associated with poorer overall survival in lung cancer patients (HR = 1.71, 95%CI 1.24-2.37, P = 0.001). Subgroup analysis by histological type showed that high CHI3L1 expression was independently associated with poorer overall survival in both non small-cell lung cancer patients (HR = 2.23,95%CI 1.43-3.47, P < 0.001) and small-cell lung cancer patients (HR = 1.45, 95%CI 1.06-2.00, P = 0.021). In addition, sensitivity analysis by omitting single study by turns did not change the pooled outcomes obviously. CONCLUSION: Our results suggest that elevated serum CHI3L1 concentration is an independent prognostic biomarker for poorer survival in lung cancer patients. PMID- 26828594 TI - Identification of 14-3-3 Proteins Phosphopeptide-Binding Specificity Using an Affinity-Based Computational Approach. AB - The 14-3-3 proteins are a highly conserved family of homodimeric and heterodimeric molecules, expressed in all eukaryotic cells. In human cells, this family consists of seven distinct but highly homologous 14-3-3 isoforms. 14-3 3sigma is the only isoform directly linked to cancer in epithelial cells, which is regulated by major tumor suppressor genes. For each 14-3-3 isoform, we have 1,000 peptide motifs with experimental binding affinity values. In this paper, we present a novel method for identifying peptide motifs binding to 14-3-3sigma isoform. First, we propose a sampling criteria to build a predictor for each new peptide sequence. Then, we select nine physicochemical properties of amino acids to describe each peptide motif. We also use auto-cross covariance to extract correlative properties of amino acids in any two positions. Finally, we consider elastic net to predict affinity values of peptide motifs, based on ridge regression and least absolute shrinkage and selection operator (LASSO). Our method tests on the 1,000 known peptide motifs binding to seven 14-3-3 isoforms. On the 14-3-3sigma isoform, our method has overall pearson-product-moment correlation coefficient (PCC) and root mean squared error (RMSE) values of 0.84 and 252.31 for N-terminal sublibrary, and 0.77 and 269.13 for C-terminal sublibrary. We predict affinity values of 16,000 peptide sequences and relative binding ability across six permutated positions similar with experimental values. We identify phosphopeptides that preferentially bind to 14-3-3sigma over other isoforms. Several positions on peptide motifs are in the same amino acid category with experimental substrate specificity of phosphopeptides binding to 14-3 3sigma. Our method is fast and reliable and is a general computational method that can be used in peptide-protein binding identification in proteomics research. PMID- 26828596 TI - Management and Outcome of Borderline Common Bile Duct with Stones: A Prospective Randomized Study. AB - INTRODUCTION: Management of common bile duct stones (CBDS) in patients with borderline CBD presents a surgical challenge. The aim of this study was to compare conservative treatment with endoscopic stone extraction for the treatment of borderline CBD with stones. PATIENTS AND METHODS: This prospective randomized controlled trial includes patients with CBDS in borderline CBD (CBD <10 mm) associated with gallbladder stones who were treated with conservative treatment or endoscopic stone extraction followed by laparoscopic cholecystectomy (LC) and intraoperative cholangiogram (IOC). The primary outcome was successful CBD clearance. The secondary outcomes were the overall complications, cost, and hospital stay. RESULTS: LC and IOC revealed complete clearance of CBDS in 48 (96%) cases in the endoscopic retrograde cholangiopancreatography (ERCP) group (52% of patients by ERCP, and 44% of patient passed the stone spontaneously), and in the remaining two patients, the CBDS was removed by transcystic exploration. In the conservative group, LC and IOC revealed complete clearance of CBDS in 90% of cases, and in the remaining 10% of patients, the CBDS was removed by transcystic exploration. Post-ERCP pancreatitis (PEP) is noticed significantly in the ERCP group (2 [4%] versus 8 [16%]; P = .04). The average net cost was significantly higher in the ERCP group. Recurrent biliary symptoms developed significantly in the ERCP group after 1 year (10% versus 0%; P = .02) in the form of recurrent cholangititis and recurrent CBDS. CONCLUSIONS: Management of CBDS in patients with borderline CBD represents a surgical challenge. Borderline CBD increases the technical difficulty of ERCP and increases the risk of PEP. Conservative management of CBDS in borderline CBD not only avoids the risks inherent in ERCP and unnecessary preoperative ERCP, but it is also effective in clearing CBDS. The hepatobiliary surgeon should consider a conservative line of treatment in CBDS in borderline CBD in order to decrease the cost and avoid unnecessary ERCP. PMID- 26828598 TI - CONSERVATION OF FLUID PREDICTED FROM STRUCTURE OF INTELLECT AND CONCEPTUAL STYLE. AB - In a translation of Piaget's developmental psychology into psychometric and structure of intellect terms, 133 children of CA 69-87 mos., equally divided by sex, were individually given a six-step conservation of fluid series, scored in points, with 18 psychometric tests and 3 conceptual style tasks. Zero order correlation and stepwise multiple regression analyses were used to determine best predictors of conservation: tests having picture-semantic content (WISC Picture Arrangement, Nebraska-Picture Association), and semantic (WISC Vocabulary, Arithmetic) and which required the convergent production operation. Contrary to hypothesis, tests with purely figural content did not predict, nor did conceptual style. PMID- 26828599 TI - STABLE AND DYNAMIC COMPONENTS OF SELF-REPORT SELF-CONCEPT. AB - Principal components analysis of semmbic differential responses of university freshmen to the concepts MY PAST, MY FUTURE, MY REAL SELF, and MY IDEAL SELF on 15 bipolar adjective scales revealed two types of components. Consktency of response to evaluative scales was found within the stimulus concept, with approximate independence across concepts. Descriptive scales showed consisteney across the four concepts and approximate independence from other descriptive scales. Independent analyses by sex produced striking similarilty of component patterns, with a few additional sex specific components appearing. The synnatic findings suggest that phenomenal self consists of phenomenally stable self descriptions and phenomenally dynamic self-evaluations. PMID- 26828600 TI - ODOUR SIMILARITIES AND THEIR MULTIDIMENSIONAL METRIC REPRESENTATION. AB - Odour qualitative similarities were collected on 18 Ss, using 10 diverse stimuli. Responses were in numerical category scale form, and were analyzed individually and pooled, by a nonmetric multidimensional scaling program TORSCA. It is suggested that the data are consistent with a degenerate metric space configuration here called a reflected simplex. Implications for psycho-physical odour quality typologies are noted. PMID- 26828597 TI - Effect of O. porcinus Tick Salivary Gland Extract on the African Swine Fever Virus Infection in Domestic Pig. AB - African swine fever is a haemorrhagic disease in pig production that can have disastrous financial consequences for farming. No vaccines are currently available and animal slaughtering or area zoning to restrict risk-related movements are the only effective measures to prevent the spread of the disease. Ornithodoros soft ticks are known to transmit the African swine fever virus (ASFV) to pigs in farms, following the natural epidemiologic cycle of the virus. Tick saliva has been shown to modulate the host physiological and immunological responses during feeding on skin, thus affecting viral infection. To better understand the interaction between soft tick, ASFV and pig at the bite location and the possible influence of tick saliva on pig infection by ASFV, salivary gland extract (SGE) of Ornithodoros porcinus, co-inoculated or not with ASFV, was used for intradermal auricular inoculation. Our results showed that, after the virus triggered the disease, pigs inoculated with virus and SGE presented greater hyperthermia than pigs inoculated with virus alone. The density of Langerhans cells was modulated at the tick bite or inoculation site, either through recruitment by ASFV or inhibition by SGE. Additionally, SGE and virus induced macrophage recruitment each. This effect was enhanced when they were co inoculated. Finally, the co-inoculation of SGE and virus delayed the early local spread of virus to the first lymph node on the inoculation side. This study has shown that the effect of SGE was powerful enough to be quantified in pig both on the systemic and local immune response. We believe this model should be developed with infected tick and could improve knowledge of both tick vector competence and tick saliva immunomodulation. PMID- 26828601 TI - SOME DIFFERENCES IN COGNITIVE ABILITIES BETWEEN SELECTED CANADIAN AND FILIPINO STUDENTS. AB - This study was designed to compare both profiles of mean performance and relationships between performances on cognitive tasks in groups of children and adolescents in Canada and The Philippines with similar educational experience. A battery of eighteen tests, including the Raven's Progressive Matrices (1968), the SRA Primary Mental Abilities Tests, and selected tests from the ETS kit, was used. The samples included 219 students from an urban centre in Ontario, boys, and girls in grades 6 and 8 from private, public, and Catholic schools, and 203 students in Manila from similar sources. The results demonstrate the existence of two general factors of intellectual funotioning, one concerned with conceptual or relational thinking and the other with forming associations. There was a marked difference between the profiles of mean factor scores for the Canadian and Filipino groups, but an equally marked similarity within groups. PMID- 26828602 TI - A CASE FOR THE USE OF MULTIVARIATE ANALYSIS IN CONCEPT GROUPING, DOMINANCE LEVEL, AND SEX AS RELATED TO VERBAL RECALL. AB - Effect of concept grouping (A), dominance level (B), and sex (C) on immediate venbal recall was investigated using a univariate and a multivariate analysis of covariance (ANCOV and MANCOV) respectively, with digit span as a concomitant variable. 138 adult Ss, 56 males and 82 females, participated in this experiment. The MANCOV in 23 factorial design showed A, C, and A x B as significant beyond the .05 level. The covariate effect was also significant. The confounding of the variance due to the neglect of sex effecbs and the lack of appropriate analytic technique in t.he previous studies using concept forma4ion materials are proposed to account for the differences in results. PMID- 26828603 TI - ANALYSIS AND REDUCTION OF COMPONENTS OF SYSTEMATIC ERROR IN RATINGS '. AB - A formal model of rating behavior was deveioped in which true and systematic error components of ratings were differentiated. A general error reduction procedure was developed, and the effects of the transformation of ratings on the validity of inter-rater agreement were analyzed within a computer simulation methodology. The method of mathematical mode1 simulation allowed the error reduction procedure to be validated, and the interactive effects of various components of error were demonstrated. Specifically, it was shown that characteristics of both the perceiver (rater) and the perceived person were invalidating sources of error which were reduced by the data reduction procedure. The proposition that the method of mathematical model simulation will prove valuable in the analysis of more complex psychological phenomena was advanced. PMID- 26828604 TI - EVIDENCE ON THE SIMPLE STRUCTURE AND FACTOR INVARIANCE ACHIEVED BY FIVE ROTATIONAL METHODS ON FOUR TYPES OF DATA. AB - Five methods of factor rotation-Maxplane, Oblimax, Promax, Harris- Kaiser, and Varimax-were applied to four types of data-questionnaire, objeckive test, a physical problem, and a plasmode. In addition, the Maxplane procedure was followed in each case by Rotoplot-assisted visual robations. The results were compared with respect to simple structure (hyperplane percentages) and factor invaniance (congruence coefficient). It was concluded that, in general, the oblique methods were superior to Varimax in terms of simple structure although not consistently in terms of factor invariance. Among the oblique methods, the Rotoplot-assisted Maxplane usually resulted in the maximum simple structure at the f .10 hyperplane width but not consistently at either of the other two arbitrarily chosen widths. The unassisted Maxplane was generally excelled by the less expensive oblique methods both wiith respect to hyperplane count and factor invariance. The Harris-Kaiser method was generally more satisfadory in terms of the two criteria combined. PMID- 26828605 TI - MAXIMAL DECOMPOSITION: AN ALTERNATIVE TO FACTOR ANALYSIS. AB - This paper considers the problem of using a subset of variables to account for a maximum amount of variance in the entire set. An approximate solution for the best possible subset of any given size is presented and theorems related to obtaining equivalent solutions are given. A variation on the method is pre- sented as a partial answer to the problem of defining common and unique variance in a solution without communalities. PMID- 26828606 TI - THE PERCEPTION OF PERSONALITY THROUGH TRAIT SORTING: A COMPARISON OF TRAIT SAMPLING TECHNIQUES. AB - This study was designed to extend the work of Rosenberg, Nelson, and Vivekananthan (1968) on the multidimensional structure of personality impressions by replicating their study with one methodologioal change. Namely, instead of allowing subjects to use each trait in only one description, subjects were allowed to use each trait in as many descriptions as they desired. A measure of trait co-occurrence for each pair of traits was used in Kruskal's muItidimentional sealing program. Canonical correlations were used to compare the present configurations with those obtained by Rosenberg et al. (1968). The two solutions were similar. Linear multiple regression was then used to locate axes in both the two- and three-dimensional solutions for each of five independently rated properties of the traits. The nonevduative dimensiom were less orthogonal than in the Rosenberg et al. (1968) study. PMID- 26828607 TI - Impact of Menstrual Cycle on Cardiac Autonomic Function Assessed by Heart Rate Variability and Heart Rate Recovery. AB - OBJECTIVE: The purpose of the present study was to investigate autonomic tone during the follicular and luteal phases of the menstrual cycle using heart rate variability (HRV) and heart rate recovery (HRR) in healthy women. SUBJECTS AND METHODS: Thirty women aged 22-37 years with regular menstrual cycles were included in the study. The HRV and HRR were measured at the follicular and luteal phases. The HRV was obtained using the time domain method with 24-hour long-term recordings. For time domain analysis, the following were obtained: standard deviation of all normal sinus R-R intervals during 24 h (SDNN), mean of the standard deviation of all normal sinus R-R intervals for all 5-min segments (SDNN index), standard deviation of average normal sinus R-R intervals for all 5-min segments (SDANN), root mean square of the successive normal sinus R-R interval difference (rMSSD), and percentage of successive normal sinus R-R intervals longer than 50 ms (pNN50). The HRR was calculated at the first, second, and third minute of recovery after the cessation of peak exercise using a treadmill test. The paired sample t test was used for the comparison of both phases of the menstrual cycle. RESULTS: The SDNN (136 +/- 39 vs. 154 +/- 32 ms; p = 0.015) and SDANN (122 +/- 36 vs. 142 +/- 36 ms; p = 0.004) were significantly lower during the luteal phase than during the follicular phase. The HRR, rMSSD, and pNN50 were not different between the 2 phases. CONCLUSION: Parasympathetic tone markers of HRV and HRR were unaffected by the menstrual phase. Lower SDNN and SDANN during the luteal phase than during the follicular phase could have resulted from enhanced sympathetic activity during the luteal phase. PMID- 26828608 TI - Pentamidine Is Not a Permeant but a Nanomolar Inhibitor of the Trypanosoma brucei Aquaglyceroporin-2. AB - The chemotherapeutic arsenal against human African trypanosomiasis, sleeping sickness, is limited and can cause severe, often fatal, side effects. One of the classic and most widely used drugs is pentamidine, an aromatic diamidine compound introduced in the 1940s. Recently, a genome-wide loss-of-function screen and a subsequently generated trypanosome knockout strain revealed a specific aquaglyceroporin, TbAQP2, to be required for high-affinity uptake of pentamidine. Yet, the underlying mechanism remained unclear. Here, we show that TbAQP2 is not a direct transporter for the di-basic, positively charged pentamidine. Even though one of the two common cation filters of aquaglyceroporins, i.e. the aromatic/arginine selectivity filter, is unconventional in TbAQP2, positively charged compounds are still excluded from passing the channel. We found, instead, that the unique selectivity filter layout renders pentamidine a nanomolar inhibitor of TbAQP2 glycerol permeability. Full, non-covalent inhibition of an aqua(glycero)porin in the nanomolar range has not been achieved before. The remarkable affinity derives from an electrostatic interaction with Asp265 and shielding from water as shown by structure-function evaluation and point mutation of Asp265. Exchange of the preceding Leu264 to arginine abolished pentamidine binding and parasites expressing this mutant were pentamidine-resistant. Our results indicate that TbAQP2 is a high-affinity receptor for pentamidine. Taken together with localization of TbAQP2 in the flagellar pocket of bloodstream trypanosomes, we propose that pentamidine uptake is by endocytosis. PMID- 26828610 TI - Plasma Rich in Growth Factors for the Treatment of Ocular Surface Diseases. AB - PURPOSE: The purpose of this work is to describe and review the technology of plasma rich in growth factors (PRGF), a novel blood derivative product, in the treatment of ocular surface disorders. METHODS: To demonstrate the importance of this technology in the treatment of ocular pathologies, a thorough review of the preclinical and clinical literature results obtained following use of the different therapeutic formulations of PRGF was carried out. A literature search for applications of PGRF plasma in the ophthalmology field was carried out using the PubMed database. RESULTS: PRGF involves the use of patient's own biologically active proteins, growth factors, and biomaterial scaffolds for therapeutic purposes. This procedural technology is gaining interest in regenerative medicine due to its potential to stimulate and accelerate the tissue healing processes. The versatility and biocompatibility of this technology opens the door to a personalized medicine on ocular tissue regeneration. This review discusses the state of the art of the new treatments and technologies developed to promote ocular surface tissue regeneration. The standardized protocol that has been developed to source eye drops from PRGF technology is also described. The preclinical research, together with the most relevant clinical applications are summarized and discussed. CONCLUSIONS: The preliminary results suggest that the use of PRGF to enhance ocular tissue regeneration is safe and efficient. PMID- 26828611 TI - Secoiridoids and other chemotaxonomically relevant compounds in Pedicularis: phytochemical analysis and comparison of Pedicularis rostratocapitata Crantz and Pedicularis verticillata L. from Dolomites. AB - We compared the respective metabolite patterns of two Pedicularis species from Dolomites. Seven phenylethanoid glycosides, i.e., verbascoside (1), echinacoside (2), angoroside A (3), cistantubuloside B1 (4), wiedemannioside C (5), campneoside II (11) and cistantubuloside C1 (12), together with several iridoid glucosides as aucubin (6), euphroside (7), monomelittoside (8), mussaenosidic acid (9) and 8-epiloganic acid (13) were identified. Pedicularis verticillata showed also the presence of greatly unexpected secoiridoids, ligustroside (14) and excelside B (15), very rare compounds in Lamiales. Both PhGs and iridoids are considered of taxonomical relevance in the Asteridae and their occurrence in Pedicularis was discussed. In particular, the exclusive presence of several compounds such as 8-epiloganic acid (13), campneoside II (11), cistantubuloside C1 (12), ligustroside (14) and excelside B (15) in Pedicularis rostratocapitata, and angoroside A (3), cistantubuloside B1 (4) and wiedemannioside C (5) in P. verticillata could be considered specific markers for the two botanical entities. PMID- 26828609 TI - Relationship between Blood Pressure and Outcomes in Acute Ischemic Stroke Patients Administered Lytic Medication in the TIMS-China Study. AB - OBJECTIVE: Increased blood pressure (BP) management following acute ischemic stroke (AIS) remains controversial. This study aimed to identify the association between BP and clinical outcomes in AIS patients administered lytic medication in the TIMS-China (thrombolysis implementation and monitor of acute ischemic stroke in China) database. METHODS: The sample comprised 1128 patients hospitalized within 4.5 hours (h) of AIS for intravenous recombinant tissue plasminogen activator (i.v. rt-PA) thrombolysis. Systolic BP (SBP) and diastolic BP (DBP) at baseline, 2 h and 24 h after treatment, and changes from baseline were analyzed. The study outcomes comprised a favorable outcome (modified Rankin Scale 0-1 at 90 days) and symptomatic intracerebral hemorrhage (SICH), analyzed using logistic regression, with low BP as the reference group. RESULTS: Lower BP (baseline, 2 h, and 24 h) was beneficial in AIS patients and significantly related to a favorable outcome (P<0.05). A substantial BP decrease at 24 h after rt-PA thrombolysis was significantly associated with a favorable outcome compared with a moderate BP decrease (P = 0.0298). A SBP >160 mmHg 2 h after rt-PA thrombolysis was significantly associated with SICH compared with a SBP <140 mmHg (P = 0.0238). An increase or no change (>25 mmHg) in SBP was significantly associated with SICH (P = 0.002) compared with a small SBP decrease (1-9 mmHg). CONCLUSIONS: This study provides novel evidence that lower BP within the first 24 h is associated with a more favorable outcome and less frequent SICH in AIS patients administered lytic medication. Routine BP-lowering treatment should be considered in AIS patients following lytic medication. PMID- 26828612 TI - Cloning, expression and localization of DacaCSP2 and DacaCSP3 during different reproductive stages in Daphnia carinata. AB - Daphnia carinata are unique freshwater crustaceans that undergo both sexual and asexual reproduction, depending on environmental factors. While the molecular mechanism behind the reproductive transformation has been unknown, chemosensory proteins (CSPs) may be involved. We have cloned the cDNA sequences of two CSP genes from D. carinata using primers based on homologous sequences and rapid amplification of cDNA ends (RACE). The full-length cDNA of DacaCSP2 (GenBank accession no: KM624608) was 632 bp, with an ORF (open reading frame) of 330 bp encoding a 12.02 kDa protein; and the full-length cDNA of DacaCSP3 (GenBank accession no: KM624609) was 935 bp, with an ORF of 342 bp encoding a 12.78kDa protein. Both CSPs encoded an N-terminal signal peptide, four conserved cysteines, an OS-D superfamily domain, a 2Fe-2S ferredoxin domain, an anaphylatoxin domain and an EGF-like domain. DaCaCSP2 and DaCaCSP3 proteins were most closely related to CSPs from Daphnia pulex and were more distantly related to CSPs from other insects. Using quantitative PCR, we found expression levels of DaCaCSP2 and DaCaCSP3 mRNA were highest in sexual females, followed by parthenogenetic females, and lowest in males. The expression levels of DaCaCSP2 and DaCaCSP3 mRNA also increased at lower temperatures, which suggested they could respond to environmental cues. Whole mount in situ hybridization (ISH) showed that DaCaCSP2 and DaCaCSP3 were expressed mainly in the ovaries, summer eggs, thoracic limbs, rectum and second antennae in sexual females; while they were expressed mainly in the ovaries, thoracic limbs, rectum and second antennae in parthenogenetic females. Together, these results suggest that DacaCSP2 and DacaCSP3 may respond to environmental cues and control the reproductive switch from sexual to asexual reproduction in D. carinata. PMID- 26828613 TI - Molecular characterization and dietary regulation of aminopeptidase N (APN) in the grass carp (Ctenopharyngodon idella). AB - Aminopeptidase N (APN) is a member of the peptidase M1 family and plays an important role in protein digestion. In the present study, an APN gene was cloned from the intestine of Ctenopharyngodon idellus. The full-length cDNA sequence of APN encodes an 892-amino-acid peptide that includes one helix trans-membrane region. Phylogenetic analysis showed that the APN sequence clustered with Danio rerio as its closest neighbor, sharing a sequence similarity of 81.5%. APN mRNA was differentially expressed in different tissues, with a gradient expression from high to low in the tissues of the fore-intestine, hind-intestine, liver, mid intestine, kidney, muscle, spleen and heart. APN expression in grass carp had a circadian pattern, showing time-dependent higher expression between 06:00 and 18:00 and lower expression between 18:00 and 06:00. In addition, the protein levels and resource in the diet-regulated APN expression suggested that low crude protein (CP) level and fish meal stimulated APN gene expression. Furthermore, the mRNA expression of APN in the intestine was significantly suppressed by high concentrations of glutamine and glutamine dipeptides, respectively. This study may provide valuable knowledge on the regulation of APN expression in teleost, which has potential applications for improving fish dietary formulations. PMID- 26828614 TI - Transcriptome modifications in human gingival fibroblasts exposed to 2 hydroxyethyl methacrylate. AB - 2-Hydroxyethyl methacrylate (HEMA),a tooth filling material, was proven to have toxic effects on different cell types, including human gingival fibroblasts (HGFs), and to be able to influence odontoblast vitality. The aim of the present study was to assess the differential transcriptome modulation induced by low HEMA concentration in cultured HGFs. RNA extracted from cultured HGFs exposed to 3 mmol/l HEMA for 24 or 96 h underwent a whole genome microarray analysis. Data analysis showed the presence of two gene clusters, composed by 310 transcripts differentially expressed after 24- and 96-h HEMA treatment compared to controls. Functional analysis demonstrated that these transcripts are mainly involved in cellular survival and death, and inflammatory response. The study highlighted an overall damage induced by HEMA exposure at both 24 and 96 h, mainly leading to a proliferation impairment. Interestingly, 24-h HEMA treatment seems to induce the cells to trigger repair mechanisms, evidencing an early compensatory response, whereas 96-h incubation appears to cause the occurrence of apoptosis as a consequence of the chronic damage. PMID- 26828615 TI - Isolation, genome sequencing and functional analysis of two T7-like coliphages of avian pathogenic Escherichia coli. AB - Avian pathogenic Escherichia coli (APEC) causes colibacillosis, which results in significant economic losses to the poultry industry worldwide. Due to the drug residues and increased antibiotic resistance caused by antibiotic use, bacteriophages and other alternative therapeutic agents are expected to control APEC infection in poultry. Two APEC phages, named P483 and P694, were isolated from the feces from the farmers market in China. We then studied their biological properties, and carried out high-throughput genome sequencing and homology analyses of these phages. Assembly results of high-throughput sequencing showed that the structures of both P483 and P694 genomes consist of linear and double stranded DNA. Results of the electron microscopy and homology analysis revealed that both P483 and P694 belong to T7-like virus which is a member of the Podoviridae family of the Caudovirales order. Comparative genomic analysis showed that most of the predicted proteins of these two phages showed strongest sequence similarity to the Enterobacteria phages BA14 and 285P, Erwinia phage FE44, and Kluyvera phage Kvp1; however, some proteins such as gp0.6a, gp1.7 and gp17 showed lower similarity (<85%) with the homologs of other phages in the T7 subgroup. We also found some unique characteristics of P483 and P694, such as the two types of the genes of P694 and no lytic activity of P694 against its host bacteria in liquid medium. Our results serve to further our understanding of phage evolution of T7-like coliphages and provide the potential application of the phages as therapeutic agents for the treatment of diseases. PMID- 26828616 TI - A pharmaceutical study on chlorzoxazone orodispersible tablets: formulation, in vitro and in-vivo evaluation. AB - CONTEXT: Muscle spasm needs prompt relief of symptoms. Chlorzoxazone is a centrally muscle relaxant. OBJECTIVES: The aim of this study was to prepare chlorzoxazone orodispersible tablets (ODTs) allowing the drug to directly enter the systemic circulation and bypassing the first-pass metabolism for both enhancing its bioavailability and exerting a rapid relief of muscular spasm. MATERIALS AND METHODS: ODTs were prepared by direct compression method using Pharmaburst(r)500, Starlac(r), Pearlitol flash(r), Prosolv(r) odt and F-melt(r) as co-processed excipients. Three ratios of the drug to the other excipients were used (0.5:1, 1:1 and 2:1). RESULTS AND DISCUSSION: All ODTs were within the pharmacopeial limits for weight and content. ODTs containing Pharmaburst(r)500 showed the shortest wetting time (~45.33 s), disintegration time (DT) (~43.33 s) and dissolution (Q15min 100.63%). By increasing the ratio of CLZ: Pharmaburst(r)500 from 0.5:1 to 1:1 and 2:1, the DT increased from 26.43 to 28.0 and 43.33 s, respectively. By using Prosolv(r) odt, ODTs failed to disintegrate in an acceptable time >180 s. DT of ODTs using different co-processed excipients can be arranged as follows: Pharmaburst(r) 500 < F-melt(r) 3 cm). Decompression was used to release intraluminal pressure and decrease the volume of the lesion. Three-dimensional computed tomography was applied to all patients at the diagnosis stage and at 6 months after decompression. Volumetric analysis was performed using software designed for 3 dimensional measurement of volumes. Other variables, such as age, gender, and rate of decrease, were recorded. RESULTS: There were important differences in rates of decrease between preoperative and 6-month lesion volumes. Statistical analyses showed no significant differences among groups for age, gender, and histologic lesion type (P > .05). CONCLUSION: Decompression of large cystic lesions could be useful for surgical interventions without complications. PMID- 26828618 TI - Zoledronic Acid Treatment After Acute Spinal Cord Injury: Results of a Randomized, Placebo-Controlled Pilot Trial. AB - OBJECTIVE: To determine the effect of intravenous zoledronic acid 5 mg on the extent and course of bone loss after spinal cord injury (SCI). DESIGN: Double blind, randomized, placebo-controlled parallel-group trial. SETTING: Acute in patient, tertiary-care rehabilitation hospital. PARTICIPANTS: Convenience sample of 17 in-patients with SCI <12 weeks before randomization; American Spinal Injury Association Impairment scale A, B, or C and medically stable. Twelve patients were evaluated at the primary endpoint at 6 months. METHODS: Patients meeting study criteria were randomly assigned to zoledronic acid 5 mg or matching placebo. Dual x-ray absorptiometry scan and serum for bone markers (type 1 procollagen amino-terminal propeptide, bone-specific alkaline phosphatase, collagen type 1 cross-linked C-telopeptide) were obtained at baseline and after 3 months, 6 months, and the every 6 months for up to 2 years. MAIN OUTCOME MEASURES: The primary endpoint was change in bone mineral density (BMD) at the total hip after 6 months; secondary endpoints were changes in BMD at other skeletal sites and changes in levels of serum bone markers. RESULTS: The group treated with zoledronic acid had a smaller decrease in BMD at 6 months at the total hip than the placebo group (right: -2.2 +/- 3.4% versus -8.6 +/- 3.5%, respectively, P = .03; left: -3.7 +/- 1.0% versus -12.3 +/- 6.9%, P = .03). Differences in BMD at the femoral neck were similar (right: -5.1 +/- 6.5% versus 20.0 +/- 6.4%, P = .01; left: -1.1 +/- 3.5% versus -11.1 +/- 7.4%, P = .02) with larger bone loss and smaller between group differences at the knee. Zoledronic acid resulted in a decrease in serum levels of both formation and resorption markers. CONCLUSIONS: Zoledronic acid is effective at mitigating bone loss after SCI. Duration of efficacy and activity at different skeletal sites may differ from that observed in able-bodied individuals and needs further study. PMID- 26828619 TI - RASCAL: A Randomized Approach for Coevolutionary Analysis. AB - A popular method for coevolutionary inference is cophylogenetic reconstruction where the branch length of the phylogenies have been previously derived. This approach, unlike the more generalized reconstruction techniques that are NP-Hard, can reconcile the shared evolutionary history of a pair of phylogenetic trees in polynomial time. This approach, while proven to be highly successful, requires a high polynomial running time. This is quickly becoming a limiting factor of this approach due to the continual increase in size of coevolutionary data sets. One existing method that combats this issue proposes a trade-off of accuracy for an asymptotic time complexity reduction. This technique in almost 70% of cases converges on Pareto optimal solutions in linear time. We build on this prior work by proposing an alternate linear time algorithm (RASCAL) that offers a significant accuracy increase, with RASCAL converging on Pareto optimal solutions in 85% of cases and unlike prior methods can ensure, with high probability, that all optimal solutions can be recovered, provided sufficient replicates are performed. PMID- 26828620 TI - Deodorization of pig manure using lignin peroxidase with different electron acceptors. AB - Odor pollution is a big environmental problem caused by large-scale livestock production in China, and developing a practical way to reduce these odors is pressing. In this study, a combination of 0.2-1.0 U/mL lignin peroxidase (LiP) and one of three peroxides (H2O2, CaO2, 2Na3CO3.3H2O2) was examined for its efficiency in reducing the release of eight chemicals (propionic acid, isobutyric acid, isocaproic acid, isovaleric acid, phenol, p-cresol, indole, and skatole), NH3, H2S, and odor intensity from pig manure. The results showed an approximately 90% reduction in p-cresol, 40-60% reduction in odor intensity, 16.5-40% reduction in indolic compounds, and 25-40% reduction in volatile fatty acids. Being the electron acceptors of LiP, 2Na3CO3.3H2O2 and CaO2 performed better than H2O2 in reducing the concentration of eight chemicals, NH3, H2S, and odor intensity from pig manure. The effect of deodorization can last for up to 72 hr. IMPLICATIONS: In China, one of the major environmental problems caused by confined feeding is odor pollution, which brings a major threat to the sustainability, profitability, and growth of the livestock industry. To couple the LiP with the electron acceptors, a low-cost, simple, and feasible method for odor removal was established in this study. Based on the study results, a practical treatment method was provided for odor pollution and supply the farm operators a more flexible time to dispose treated manure. PMID- 26828621 TI - Molecular characterization of soil organic matter from native vegetation-pasture sugarcane transitions in Brazil. AB - Replacing pastures (PA) with sugarcane (SG) has been deemed an agronomically feasible strategy for sugarcane expansion in Brazil. However, there are some uncertainties about the environmental impacts regarding this land use change (LUC), mainly related to soil organic matter (SOM), a key factor of environmental sustainability of Brazilian ethanol. LUC-related losses of SOM can overcome the C savings from biofuels. The molecular composition of SOM was evaluated to understand the C dynamics regarding LUC from PA to SG, using native vegetation (NV) as reference. Our study area was located in the south-central region of Brazil. Soil sampling was performed at three depths (0-0.1m, 0.2-0.3m and 0.9-1m) in three representative sites with known LUC history and management practice since 1970. Pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) was chosen to study SOM chemistry. Content and isotopic composition of soil organic C and N were also determined. The LUC caused decreases on C and N contents and on delta(13)C isotopic values. Depth was the major factor that influenced SOM composition, while the influence of LUC was mainly evident in surface soils and diminished rapidly with depth. The main difference in SOM composition undergoing the conversion PA-SG was a higher contribution from compounds associated to fresh litter inputs. The high contribution from fresh litter, having a relatively low mean residence time and increasing decomposition rates, is probably a major factor that drives C losses in areas undergoing sugarcane expansion. PMID- 26828622 TI - Exposure to lithium through drinking water and calcium homeostasis during pregnancy: A longitudinal study. AB - There is increasing evidence of adverse health effects due to elevated lithium exposure through drinking water but the impact on calcium homeostasis is unknown. This study aimed at elucidating if lithium exposure through drinking water during pregnancy may impair the maternal calcium homeostasis. In a population-based mother-child cohort in the Argentinean Andes (n=178), with elevated lithium concentrations in the drinking water (5-1660MUg/L), blood lithium concentrations (correlating significantly with lithium in water, urine and plasma) were measured repeatedly during pregnancy by inductively coupled plasma mass spectrometry and used as exposure biomarker. Markers of calcium homeostasis included: plasma 25 hydroxyvitamin D3, serum parathyroid hormone (PTH), and calcium, phosphorus and magnesium concentrations in serum and urine. The median maternal blood lithium concentration was 25MUg/L (range 1.9-145). In multivariable-adjusted mixed effects linear regression models, blood lithium was inversely associated with 25 hydroxyvitamin D3 (-6.1nmol/L [95%CI -9.5; -2.6] for a 25MUg/L increment in blood lithium). The estimate increased markedly with increasing percentiles of 25 hydroxyvitamin D3. In multivariable-adjusted mixed-effects logistic regression models, the odds ratio of having 25-hydroxyvitamin D3<30nmol/L (19% of the women) was 4.6 (95%CI 1.1; 19.3) for a 25MUg/L increment in blood lithium. Blood lithium was also positively associated with serum magnesium, but not with serum calcium and PTH, and inversely associated with urinary calcium and magnesium. In conclusion, our study suggests that lithium exposure through drinking water during pregnancy may impair the calcium homeostasis, particularly vitamin D. The results reinforce the need for better control of lithium in drinking water, including bottled water. PMID- 26828623 TI - Occurrence and prenatal exposure to persistent organic pollutants using meconium in Korea: Feasibility of meconium as a non-invasive human matrix. AB - Prenatal exposure to persistent organic pollutants (POPs) is of great concern due to the vulnerability of fetus. Nineteen Polychlorinated biphenyls (PCBs), 18 organochlorine pesticides (OCPs) including DDTs, HCHs, chlordanes, and hexachlorobenzene, and 22 polybrominated diphenyl ethers (PBDEs) were measured in meconium samples from 72 newborn infants using high resolution gas chromatography/mass spectrometry. The median concentrations (on wet weight basis) of PCBs, OCPs, and PBDEs were 26.8pg/g, 66.7pg/g, and 2.32pg/g, respectively. Highly significant correlations were observed among the compounds of PCBs and OCPs, suggesting their similar sources and kinetic behaviors. BDE 47 had significant correlations with PCBs and OCPs, whereas BDE 209 was not correlated with any of the contaminants due to different exposure sources. The concentrations of p,p'-DDE, beta-HCH, and trans-nonaCHL between paired maternal blood-meconium and cord blood-meconium showed significant correlations, while PCBs and PBDEs were not significantly correlated in the paired samples. Maternal age and gestational age were demographic parameters affecting POP levels in meconium. Multiple regression analysis showed that the levels of several OCPs in cord and maternal serum were contributing factors governing the levels of these contaminants in meconium. Our results indicate that meconium can be utilized as a human matrix for prenatal exposure to several OCPs. PMID- 26828624 TI - Low-level arsenic exposure: Nutritional and dietary predictors in first-grade Uruguayan children. AB - Arsenic exposure in children is a public health concern but is understudied in relation to the predictors, and effects of low-level exposure. We examined the extent and dietary predictors of exposure to inorganic arsenic in 5-8 year old children from Montevideo, Uruguay. Children were recruited at school; 357 were enrolled, 328 collected morning urine samples, and 317 had two 24-h dietary recalls. Urinary arsenic metabolites, i.e. inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA), were measured using high-performance liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICP-MS), and the sum concentration (U-As) used for exposure assessment. Proportions of arsenic metabolites (%iAs, %MMA and %DMA) in urine were modelled in OLS regressions as functions of food groups, dietary patterns, nutrient intake, and nutritional status. Exposure to arsenic was low (median U As: 9.9ug/L) and household water (water As: median 0.45ug/L) was not a major contributor to exposure. Children with higher consumption of rice had higher U-As but lower %iAs, %MMA, and higher %DMA. Children with higher meat consumption had lower %iAs and higher %DMA. Higher scores on "nutrient dense" dietary pattern were related to lower %iAs and %MMA, and higher %DMA. Higher intake of dietary folate was associated with lower %MMA and higher %DMA. Overweight children had lower %MMA and higher %DMA than normal-weight children. In summary, rice was an important predictor of exposure to inorganic arsenic and DMA. Higher meat and folate consumption, diet rich in green leafy and red-orange vegetables and eggs, and higher BMI contributed to higher arsenic methylation capacity. PMID- 26828625 TI - The relationship of age and place of delivery with postpartum contraception prior to discharge in Mexico: A retrospective cohort study. AB - OBJECTIVES: To test the association of age (adolescents vs. older women) and place of delivery with receipt of immediate postpartum contraception in Mexico. STUDY DESIGN: Retrospective cohort study, Mexico, nationally representative sample of women 12-39years old at last delivery. We used multivariable logistic regression to test the association of self-reported receipt of postpartum contraception prior to discharge with age and place of delivery (public, employment based, private, or out of facility). We included individual and household-level confounders and calculated relative and absolute multivariable estimates of association. RESULTS: Our analytic sample included 7022 women (population, N=9,881,470). Twenty percent of the population was 12-19years old at last birth, 55% aged 20-29 and 25% 30-39years old. Overall, 43% of women reported no postpartum contraceptive method. Age was not significantly associated with receipt of a method, controlling for covariates. Women delivering in public facilities had lower odds of receipt of a method (Odds Ratio=0.52; 95% Confidence Interval (CI)=0.40-0.68) compared with employment-based insurance facilities. We estimated 76% (95% CI=74-78%) of adolescents (12-19years) who deliver in employment-based insurance facilities leave with a method compared with 59% (95% CI=56-62%) who deliver in public facilities. CONCLUSION: Both adolescents and women ages 20-39 receive postpartum contraception, but nearly half of all women receive no method. Place of delivery is correlated with receipt of postpartum contraception, with lower rates in the public sector. Lessons learned from Mexico are relevant to other countries seeking to improve adolescent health through reducing unintended pregnancy. IMPLICATIONS: Adolescents receive postpartum contraception as often as older women in Mexico, but half of all women receive no method. PMID- 26828627 TI - Minimal energy eMatrix treatment combined with elure application for an expedited response in the treatment of hyperpigmentation and overall facial skin rejuvenation: A case report series. AB - In order to minimize the side effects of the eMatrix Sublative Rejuvenation procedure, the low-energy setting was employed; and to increase the efficacy of this procedure, elure anti-pigment topical was applied immediately after the eMatrix procedure. This combination resulted in significant improvement in facial pigmentation and global rejuvenation with minimal side effects. PMID- 26828626 TI - Gut microbiome as a novel cardiovascular therapeutic target. AB - Over the last two decades, our understanding of gut microbiotal composition and its association with intra-intestinal and extra-intestinal diseases including risk factors of cardiovascular disease (CVD) namely metabolic syndrome and atherosclerosis, have been increased exponentially. A pertinent question which often arises in researchers' community is on how to manipulate the gut microbial ecology to 'cure' the cardiovascular risk factors. Accordingly, in this review we summarized the potential strategies, based on our current knowledge on gut microbiota in modulating CVD, how gut microbiota can be therapeutically exploited by targeting their metabolic activity to alleviate the risk factors of CVD. PMID- 26828628 TI - There and Back Again: Parallel Evolution of Cell Coverings in Centrohelid Heliozoans. AB - Centrohelid heliozoans are non-ciliary axopodial protists of uncertain affinities. Cell coverings (organic spicules, siliceous plate-scales and spine scales) are the main character for their taxonomy. Phylogenetic reconstructions of this group are mostly based on the sequences of 18S rDNA. Here molecular and microscopical data on Raphidiophrys heterophryoidea, R. drakena sp. nov., Spiculophrys agregata gen. et sp. nov. and four strains here referred to as Heterophrys-like organisms (HLOs) are provided. The family Raphidiophryidae is shown to be polyphyletic. The position of Spiculophrys is uncertain, but it probably represents the most basal branch in the order Pterocystida. Three strains of HLOs branch deeply inside the genus Acanthocystis and one strain inside Polyplacocystis, even though they differ considerably in morphology of the cell coverings from other members of these two genera. The possible reasons for this phenomenon are discussed. On the basis of newly obtained sequences and EDX analysis an interpretation of the evolution of cell coverings is proposed. It appears that cell coverings were ancestrally organic, then silicified independently on two occasions and after that multiple cases of desilicification or even complete loss of coverings took place. So, in the two centrohelid orders the evolution includes similar sequences of parallel events. PMID- 26828629 TI - Myofibrillar Myopathy Presenting as Neonatal Intestinal Pseudo-Obstruction: An Extremely Rare Entity. AB - BACKGROUND: Although the most common cause of neonatal intestinal pseudoobstruction (IP) is Hirschprungs disease, rarely myofibrillar myopathy can cause the same. CASE REPORT: This 31+4/7 male infant at autopsy had marked narrowing of the jejunum (0.9 cm long), and colon (7.0 cm long) markedly narrowed segments of the jejunum and large intestine, were noted respectively. Sections from these segments showed eosinophilic periodic acid Schiff stain and desmin positive cytoplasmic inclusion bodies in the myocytes. Transmission electron microscopy performed revealed the presence of abnormal granulofilamentous material around the atrophic sarcomeres, subsarcolemmal rod-shaped and globoid fibrillar inclusions in the intestinal, skeletal, and cardiac myocytes, suggesting a myofibrillar myopathy. CONCLUSION: Pure phenotypic neonatal IP presentation in a myofibrillar myopathy is extremely rare and not reported in the literature. Along with other common causes of neonatal IP, neuromuscular causes should also be investigated. PMID- 26828631 TI - Intramuscular Autotransplantation of Vitrified Rat Ovary Encapsulated with Hyaluronic Acid Hydrogel. AB - Acceleration of revival of ovarian function and maintaining of follicular reserve is mandatory after transplantation of cryopreserved ovarian tissue. In this study, hyaluronic acid hydrogel was used as a scaffold to improve restoration of ovarian estrous cycle and follicular preservation. Mature (~ 8 weeks old) female Wistar rats with normal estrous cycles were divided in two groups: A: autotransplanted vitrified ovarian tissue without hyaluronic acid (HA), and B: autotransplanted vitrified ovarian tissue encapsulated with HA. Bilateral ovariectomy was performed in the diestrus stage; then ovaries were vitrified, warmed, and autotransplanted intramuscularly. Daily vaginal monitoring was performed until re-initiation of first full estrous cycle. Thereafter, follicular preservation, fibrosis, and apoptosis incidence were assessed histologically and immunohistochemically. The serum follicle stimulating hormone (FSH) levels were also accessed and compared for normal and ovariectomized rats. Re-initiation of first full cycle, atretic follicles, apoptotic index, and area of fibrosis in group A were approximately similar to group B. However, the total numbers of intact follicles were significantly lower in group B than group A. Moreover, the level of FSH in both experimental groups and normal rats was similar and in group B reduced significantly compared to the ovariectomized rats. Hyaluronic acid hydrogel did not show any negative effect on restoration of estrous cycle, but could not support follicular preservation after autotransplantation. PMID- 26828630 TI - The Influence of Antenatal Partner Support on Pregnancy Outcomes. AB - BACKGROUND: While there has been considerable attention given to the multitude of maternal factors that contribute to perinatal conditions and poor birth outcomes, few studies have aimed to understand the impact of fathers or partners. We examined associations of antenatal partner support with psychological variables, smoking behavior, and pregnancy outcomes in two socioeconomically distinct prebirth cohorts. MATERIALS AND METHODS: Data were from 1764 women recruited from an urban-suburban group practice (Project Viva) and 877 women from urban community health centers (Project ACCESS), both in the Boston area. Antenatal partner support was assessed by the Turner Support Scale. Multivariable linear and logistic regression analyses determined the impact of low antenatal partner support on the outcomes of interest. RESULTS: In early pregnancy, 6.4% of Viva and 23.0% of ACCESS participants reported low partner support. After adjustment, low partner support was cross-sectionally associated with high pregnancy-related anxiety in both cohorts (Viva AOR 1.8; 95% CI: 1.0-3.4 and ACCESS AOR 1.9; 95% CI: 1.1-3.3) and with depression in ACCESS (AOR 1.9; 95% CI: 1.1-3.3). In Viva, low partner support was also related to depression mid-pregnancy (AOR 3.1; 95% CI: 1.7-5.7) and to smoking (AOR 2.2; 95% CI: 1.3-3.8). Birth weight, gestational age, and fetal growth were not associated with partner support. CONCLUSIONS: This study of two economically and ethnically distinct cohorts in the Boston area highlights higher levels of antenatal anxiety, depression, and smoking among pregnant women who report low partner support. Partner support may be an important and potentially modifiable target for interventions to improve pregnancy outcomes. PMID- 26828632 TI - Identification of novel extracellular protein for PCB/biphenyl metabolism in Rhodococcus jostii RHA1. AB - Rhodococcus jostii RHA1 (RHA1) degrades polychlorinated biphenyl (PCB) via co metabolism with biphenyl. To identify the novel open reading frames (ORFs) that contribute to PCB/biphenyl metabolism in RHA1, we compared chromatin immunoprecipitation chip and transcriptomic data. Six novel ORFs involved in PCB/biphenyl metabolism were identified. Gene deletion mutants of these 6 ORFs were made and were tested for their ability to grow on biphenyl. Interestingly, only the ro10225 deletion mutant showed deficient growth on biphenyl. Analysis of Ro10225 protein function showed that growth of the ro10225 deletion mutant on biphenyl was recovered when exogenous recombinant Ro10225 protein was added to the culture medium. Although Ro10225 protein has no putative secretion signal sequence, partially degraded Ro10225 protein was detected in conditioned medium from wild-type RHA1 grown on biphenyl. This Ro10225 fragment appeared to form a complex with another PCB/biphenyl oxidation enzyme. These results indicated that Ro10225 protein is essential for the formation of the PCB/biphenyl dioxygenase complex in RHA1. PMID- 26828633 TI - Facile Synthesis of Core/Shell-like NiCo2O4-Decorated MWCNTs and its Excellent Electrocatalytic Activity for Methanol Oxidation. AB - The design and development of an economic and highly active non-precious electrocatalyst for methanol electrooxidation is challenging due to expensiveness of the precursors as well as processes and non-ecofriendliness. In this study, a facile preparation of core-shell-like NiCo2O4 decorated MWCNTs based on a dry synthesis technique was proposed. The synthesized NiCo2O4/MWCNTs were characterized by infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and selected area energy dispersive spectrum. The bimetal oxide nanoparticles with an average size of 6 +/ 2 nm were homogeneously distributed onto the surface of the MWCNTs to form a core-shell-like nanostructure. The NiCo2O4/MWCNTs exhibited excellent electrocatalytic activity for the oxidation of methanol in an alkaline solution. The NiCo2O4/MWCNTs exhibited remarkably higher current density of 327 mA/cm(2) and a lower onset potential of 0.128 V in 1.0 M KOH with as high as 5.0 M methanol. The impressive electrocatalytic activity of the NiCo2O4/MWCNTs is promising for development of direct methanol fuel cell based on non-Pt catalysts. PMID- 26828635 TI - PTSD and Daily Co-Occurrence of Drug and Alcohol Use Among Women Experiencing Intimate Partner Violence. AB - OBJECTIVE: People with posttraumatic stress disorder (PTSD) are at high risk for substance use, and PTSD is common among women experiencing intimate partner violence. Considering the effects of both PTSD and substance use, such as poorer treatment outcomes and greater health/behavior problems, women experiencing intimate partner violence are a high-risk, under-researched group. METHODS: We utilized a micro-longitudinal study design to assess daily drug and alcohol use over 21 days among 41 women experiencing intimate partner violence recruited from the community. RESULTS: Participants were about 45 years old (M = 45.1, SD = 8.5) and mostly African American (n = 32, 78%). Co-occurrence of drug and alcohol use was reported on 19.0% of days, while drug use alone occurred on 13.4% of days and alcohol use on 12.1%. Fifteen percent of participants met current PTSD criteria, with a mean symptom severity rating of 15.90 (SD = 10.94, range 0 to 47). Women with PTSD, compared to those without, were nearly 15 times more likely to have days of co-occurrence of drug and alcohol use (p = .037) and nearly 7 times more likely to have days of drug use alone (p = .044). CONCLUSIONS: These findings indicate that the combination of intimate partner violence and PTSD may make women especially prone to daily co-occurring drug and alcohol use or drug use alone. Further research is needed to explore this association and examine the need for integrated programs to support victims' health, prevent the development of substance use problems, and facilitate recovery from PTSD and substance use. PMID- 26828636 TI - Iron-Mediated One-Pot Synthesis of 3,5-Diarylpyridines from beta-Nitrostyrenes. AB - An operationally simple and mild one-pot protocol for the synthesis of a variety of 3,5-diarylpyridines from beta-nitrostyrenes was achieved by using elemental iron. This reaction proceeds via reduction of the nitro group, resulting in in situ imine formation followed by trimolecular condensation with concomitant debenzylative aromatization. By employing this method, a series of symmetrical and unsymmetrical 3,5-diarylpyridines were synthesized with good to excellent yields. In addition, this method was also utilized for the synthesis of Sch 21418, an anti-inflammatory agent on gram scale. PMID- 26828634 TI - Long-term effects of adolescent exposure to bisphenol A on neuron and glia number in the rat prefrontal cortex: Differences between the sexes and cell type. AB - Bisphenol A (BPA), an endocrine disruptor used in a variety of consumer products, has been found to alter the number of neurons in multiple brain areas in rats following exposure in perinatal development. Both the number of neurons and glia also change in the medial prefrontal cortex (mPFC) during adolescence, and this process is known to be influenced by gonadal hormones which could be altered by BPA. In the current study, we examined Long-Evans male and female rats that were administered BPA (0, 4, 40, or 400MUg/kg/day) during adolescent development (postnatal days 27-46). In adulthood (postnatal day 150), the number of neurons and glia in the mPFC were stereologically assessed in methylene blue/azure II stained sections. There were no changes in the number of neurons, but there was a significant dose by sex interaction in number of glia in the mPFC. Pairwise comparisons between controls and each dose showed a significant increase in the number of glia between 0 and 40MUg/kg/day in females, and a significant decrease in the number of glia between 0 and 4MUg/kg/day in males. In order to determine the type of glial cells that were changing in these groups in response to adolescent BPA administration, adjacent sections were labelled with S100beta (astrocytes) and IBA-1 (microglia) in the mPFC of the groups that differed. The number of microglia was significantly higher in females exposed to 40MUg/kg/day than controls and lower in males exposed to 4MUg/kg/day than controls. There were no significant effects of adolescent exposure to BPA on the number of astrocytes in male or females. Thus, adolescent exposure to BPA produced long-term alterations in the number of microglia in the mPFC of rats, the functional implications of which need to be explored. PMID- 26828637 TI - Iridium(III) Mediated Reductive Transformation of Closed-Shell Azo-Oxime to Open Shell Azo-Imine Radical Anion: Molecular and Electronic Structure, Electron Transfer, and Optoelectronic Properties. AB - The hydrogen bonded bis azo-oximato [IrCl2(L(NOH))(L(NO))] 2 and its deprotonated form (Et3NH)[IrCl2(L(NO))2] (Et3NH)(+)3(-) have been isolated in the crystalline state by a facile synthetic method. The azo-oxime frameworks in 3(-) have been conveniently transformed to the azo-imine by reduction with NaBH4 or ascorbic acid. Notably, the coordinated azo-imines accept an extra electron thereby furnishing the azo-imine radical anion complex 4. The underlying reductive transformation can be best described by proton-coupled electron transfer (PCET) process. Both the coordinated ligands (azo-oxime) in 3(-) are typically closed shell monoanion (L(NO-)), but their reduced form (azo-imine) can behave as open shell monoanion (L(NH*-)) owing to the presence of highly stabilized virtual orbitals. Remarkable enhancement of the pi-acidity in azo-imine relative to the precursor azo-oxime has also been reflected from the electrochemical study. The irido complexes display rich optoelectronic properties, and the origin of the transitions has been scrutinized by the TD-DFT method. The molecular geometries of the complexes 2 and 3(-) reveal that the syn orientation of the azo-oximes frameworks is favored because of strong noncovalent H-bonding and pi-pi stacking interactions. In the course of the reduction of 3(-), the sterically encumbered disposition of the azo-oximes is converted to the relaxed anti form in the transformed azo-imines. Diffraction study reveals the electronic structure of 4 as [Ir(III)Cl2{(L(NH))2(*-)}]. The superior stabilization of the unpaired spin on the ligand array rather than metal has also been substantiated from EPR and DFT studies. Theoretical analysis reveals that the odd electron delocalizes primarily over both the azo-imine moieties ([IrCl2(L(NH*-))(L(NH))] <-> ([IrCl2(L(NH))(L(NH*-))]) with no apparent contribution from metal, and this type of ligand-centered mixed valency (LCMV) can be best expressed as Robin-Day class III (fully delocalized) in nature. PMID- 26828638 TI - Correction to Olfactory Impact of Higher Alcohols on Red Wine Fruity Ester Aroma Expression in Model Solution. PMID- 26828639 TI - The stability and electronic properties of Pt-modified Cu(1 1 0) and Cu(1 1 1) in the absence/presence of small molecules: a density-functional theory modeling. AB - Pt-Cu bimetallic alloys, as a key component in many heterogeneous catalysts, have the potential to be used in a range of industrially important reactions. The stability of platinum-modified Cu(1 1 0) and Cu(1 1 1) surfaces in the absence/presence of CO, NO and O has been investigated based on density functional theory. We find that Pt alloyed in the second layer of the Cu (1 1 0) surface, rather than in the bulk, is the most favorable configuration. To relieve the strain, platinum tends to stay in the surface layer of close-packed Cu(1 1 1). Adsorbates can affect the stability of Pt-modified surfaces. Upon the adsorption of CO and NO, Pt segregation to the (1 1 0) surface becomes favorable, while on oxygen adsorption, no segregation occurs. Platinum only prefers to segregate on the Cu (1 1 1) surface when it is exposed to carbon monoxide, it tends to locate in the second layer for the other two adsorbates. Combining the position of d-band center, the d-bandwidth, and the separation between the bonding and antibonding states of the adsorbates, we interpret the results and correlate the relationship between the electronic properties of the substrate and the adsorption energy of the adsorbates, which could shed light on the prediction of bimetallic structures with desirable chemical properties. PMID- 26828640 TI - Problematic drinking, impulsivity, and physical IPV perpetration: A dyadic analysis. AB - Alcohol use and impulsivity are 2 known risk factors for intimate partner violence (IPV). The current study examined the independent and interactive effects of problematic drinking and 5 facets of impulsivity (i.e., negative urgency, positive urgency, sensation seeking, lack of premeditation, and lack of perseverance) on perpetration of physical IPV within a dyadic framework. Participants were 289 heavy drinking heterosexual couples (total N = 578) with a recent history of psychological and/or physical IPV recruited from 2 metropolitan U.S. cities. Parallel multilevel actor partner interdependence models were used and demonstrated actor problematic drinking, negative urgency, and lack of perseverance were associated with physical IPV. Findings also revealed associations between partner problematic drinking and physical IPV as well as significant Partner Problematic Drinking * Actor Impulsivity (Negative Urgency and Positive Urgency) interaction effects on physical IPV. Findings highlight the importance of examining IPV within a dyadic framework and are interpreted using the I3 metatheoretical model. (PsycINFO Database Record PMID- 26828642 TI - Exposure to and engagement with gambling marketing in social media: Reported impacts on moderate-risk and problem gamblers. AB - Digital advertising for gambling and specifically marketing via social media have increased in recent years, and the impact on vulnerable consumers, including moderate-risk and problem gamblers, is unknown. Social media promotions often fall outside of advertising restrictions and codes of conduct and may have an inequitable effect on susceptible gamblers. This study aimed to investigate recall of exposure to, and reported impact on gamblers of, gambling promotions and marketing content on social media, with a focus on vulnerable users currently experiencing gambling problems. Gamblers who use social media (N = 964) completed an online survey assessing their exposure to and engagement with gambling operators on social media, their problem gambling severity, and the impact of social media promotions on their gambling. Gamblers at moderate risk and problem gamblers were significantly more likely to report having been exposed to social media gambling promotions and indicated actively engaging with gambling operators via these platforms. They were more likely to self-report that they had increased gambling as a result of these promotions, and over one third reported that the promotions had increased their problems. This research suggests that gamblers at moderate risk or those experiencing gambling problems are more likely to be impacted by social media promotions, and these may play a role in exacerbating disordered gambling. Future research should verify these self-reported results with behavioral data. However, the potential influence of advertisements via these new platforms should be considered by clinicians and policymakers, given their potential role in the formation of this behavioral addiction. PMID- 26828643 TI - Insurance Coverage for Complementary Health Approaches Among Adult Users: United States, 2002 and 2012. AB - KEY FINDINGS: Data from the 2002 and 2012 National Health Interview Surveys. Between 2002 and 2012, the use of acupuncture, chiropractic, and massage therapy increased among adults who did not have health insurance coverage for these complementary health approaches. No change in use was observed among those who had coverage for these approaches. While 60% of adults who saw a practitioner for chiropractic had at least some health insurance coverage for this approach, far fewer adults seeing a practitioner for acupuncture (25%) or massage therapy (15%) had coverage for these approaches. Adults who saw practitioners for acupuncture and chiropractic-and had health insurance coverage for these approaches-were more likely to have partial than complete coverage. PMID- 26828641 TI - Attempts to stop or reduce daily cannabis use: An intensive natural history study. AB - We attempted to replicate and add to our prior study of attempts to stop or reduce cannabis use among daily cannabis users trying to change on their own, by observing a larger sample and adding further clinically relevant outcomes. Daily users (n = 193) who intended to stop or reduce sometime in the next 3 months called an Interactive Voice Response system each morning for 3 months to report on cannabis use, attempts to stop or reduce, withdrawal symptoms, and so forth, on the prior day. This study replicated our prior findings that (a) cannabis users trying to change make many, and often rapid, transitions among use as usual, reduction, and abstinence; (b) reduction attempts are more common than abstinence attempts; (c) quit and reduction attempts are short-lived and few participants achieve long-term abstinence; (d) alcohol and drug use are not greater on abstinence days; and (e) few users seek treatment. Novel findings included (f) a greater number of days of abstinence or intentional reduction predicted a greater decline in cannabis dependence, (g) most users do not prepare before their quit attempt, (h) coping outcomes during abstinence predict increased duration of abstinence, (i) tobacco use is less common on days of abstinence, and (j) withdrawal symptoms occur even with short quit attempts. Replication tests in more generalizable samples and of longer duration are indicated. Further natural history studies are likely to provide information to help improve the content of psychological treatments for cannabis use. (PsycINFO Database Record PMID- 26828644 TI - Effectiveness of rapid response teams on rates of in-hospital cardiopulmonary arrest and mortality: A systematic review and meta-analysis. AB - BACKGROUND: In 2004, the Institute for Healthcare Improvement's 100,000 Lives Campaign recommended that hospitals implement rapid response teams (RRTs) charged with identifying non-intensive care unit (ICU) patients at risk for rapid deterioration. Although RRTs are now in widespread use, there have been conflicting results regarding the impact of RRTs on hospital mortality and cardiopulmonary arrest. PURPOSE: To assess the effectiveness of RRTs on reducing hospital mortality and non-ICU cardiopulmonary arrest rates. DATA SOURCES: We conducted a systematic review using MEDLINE (1966-2014), Cochrane Central Register of Controlled Trials (1898-2014), Cumulative Index to Nursing and Allied Health Literature (1994-2014), and ClinicalTrials.gov (1997-2014) during October 2014. There were no constraints on language or publication status. DATA EXTRACTION: We included before-after studies, cohort studies, and cluster randomized trials that reported hospital mortality and/or non-ICU cardiopulmonary arrest for adults hospitalized in a non-ICU setting after the implementation of RRTs and/or medical emergency teams (METs). Data were extracted by 2 sets of 2 independent reviewers using a standardized data-collection form. Disagreements were resolved by a third reviewer. Authors were contacted to obtain any missing data. DATA SYNTHESIS: Our search identified 691 studies, of which 30 met criteria for inclusion in the analysis. Implementation of an RRT/MET was associated with a significant decrease in hospital mortality (relative risk [RR] = 0.88, 95% confidence interval [CI]: 0.83-0.93, I(2) = 86%, 3,478,952 admissions) and a significant decrease in the number of non-ICU cardiac arrests (RR = 0.62, 95% CI: 0.55-0.69, I(2) = 71%, 3,045,273 admissions). CONCLUSIONS: Implementation of an RRT/MET is associated with a reduction in both hospital mortality and non-ICU cardiopulmonary arrests. Journal of Hospital Medicine 2016;11:438-445. (c) 2016 Society of Hospital Medicine. PMID- 26828645 TI - Gene expression in the aging human brain: an overview. AB - PURPOSE OF REVIEW: The review aims to provide a summary of recent developments in the study of gene expression in the aging human brain. RECENT FINDINGS: Profiling differentially expressed genes or 'transcripts' in the human brain over the course of normal aging has provided valuable insights into the biological pathways that appear activated or suppressed in late life. Genes mediating neuroinflammation and immune system activation in particular, show significant age-related upregulation creating a state of vulnerability to neurodegenerative and neuropsychiatric disease in the aging brain. Cellular ionic dyshomeostasis and age-related decline in a host of molecular influences on synaptic efficacy may underlie neurocognitive decline in later life. Critically, these investigations have also shed light on the mobilization of protective genetic responses within the aging human brain that help determine health and disease trajectories in older age. There is growing interest in the study of pre and posttranscriptional regulators of gene expression, and the role of noncoding RNAs in particular, as mediators of the phenotypic diversity that characterizes human brain aging. SUMMARY: Gene expression studies in healthy brain aging offer an opportunity to unravel the intricately regulated cellular underpinnings of neurocognitive aging as well as disease risk and resiliency in late life. In doing so, new avenues for early intervention in age-related neurodegenerative disease could be investigated with potentially significant implications for the development of disease-modifying therapies. PMID- 26828646 TI - The relationship between fecal incontinence, constipation and defecatory symptoms in women with pelvic floor disorders. AB - AIMS: To determine if fecal incontinence (FI) is associated with constipation and defecatory symptoms in women with urinary incontinence, fecal incontinence, and pelvic organ prolapse. METHODS: Cross-sectional study of women seeking care for urinary incontinence, fecal incontinence, and pelvic organ prolapse. FI was defined as a positive response to the question, "During the last 4 weeks how often have you leaked or soiled yourself with stool?" Constipation and defecatory symptoms, including straining, sensation of incomplete emptying, and splinting, were measured using the Birmingham Bowel Symptom Questionnaire and the Colorectal Anal Distress Inventory. Prevalence and severity of constipation and defecatory symptoms were compared between women with and without FI. We performed separate multivariable regression analyses for the association of FI and constipation and defecatory symptoms while adjusting for potential confounders. RESULTS: We included 1,015 women: 422 (44%) with and 593 (56%) without FI. Women with FI compared to those without FI were more likely to report constipation (76% vs. 66%) as well as straining (53% vs. 38%), sensation of incomplete emptying (58% vs. 40%) and splinting (30% vs. 20%), all P < 0.001. Women with FI reported greater severity of constipation (4.3 +/- 4.3 vs. 3.1 +/- 3.6, P < 0.001), straining (2.7 +/- 1 vs. 2.5 +/- 0.9, P = 0.02) and sense of incomplete emptying (2.6 +/- 1 vs. 2.4 +/- 0.9, P = 0.02) than women without FI. Even after controlling for potential confounders, the diagnosis of FI was significantly associated with constipation and defecatory symptoms. CONCLUSIONS: In women with urinary incontinence, fecal incontinence, and pelvic organ prolapse, diagnosis of FI is associated with constipation and other defecatory symptoms; which impacts evaluation and management strategies. Neurourol. Urodynam. 36:495-498, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26828647 TI - A systematic review of the cost and cost-effectiveness studies of proton radiotherapy. AB - BACKGROUND: Economic analyses of new technologies, such as proton-beam radiotherapy (PBT), are a public health priority. To date, no systematic review of the cost-effectiveness of PBT has been performed. METHODS: Systematic searches of PubMed, EMBASE, abstracts from American Society for Radiation Oncology and American Society of Clinical Oncology meetings, and the Cost-Effectiveness Analysis Registry were conducted (2000-2015) along with abstracts from the Particle Therapy Co-Operative Group of North America for both years of existence (2014-2015). Eighteen original investigations were analyzed. RESULTS: The cost effectiveness for prostate cancer-the single most common diagnosis currently treated with PBT-was suboptimal. PBT was the most cost-effective option for several pediatric brain tumors. PBT costs for breast cancer were increased but were favorable for appropriately selected patients with left-sided cancers at high risk of cardiac toxicity and compared with brachytherapy for accelerated partial breast irradiation. For non-small cell lung cancer (NSCLC), the greatest cost-effectiveness benefits using PBT were observed for locoregionally advanced but not early stage-tumors. PBT offered superior cost-effectiveness in selected head/neck cancer patients at higher risk of acute mucosal toxicities. Similar cost-effectiveness was observed for PBT, enucleation, and plaque brachytherapy in patients with uveal melanoma. CONCLUSIONS: With greatly limited amounts of data, PBT offers promising cost-effectiveness for pediatric brain tumors, well-selected breast cancers, locoregionally advanced NSCLC, and high-risk head/neck cancers. Heretofore, it has not been demonstrated that PBT is cost-effective for prostate cancer or early stage NSCLC. Careful patient selection is absolutely critical to assess cost-effectiveness. Together with increasing PBT availability, clinical trial evidence, and ongoing major technological improvements, cost-effectiveness data and conclusions from this analysis could change rapidly. Cancer 2016;122:1483-501. (c) 2016 American Cancer Society. PMID- 26828648 TI - Reorganization of Respiratory Descending Pathways following Cervical Spinal Partial Section Investigated by Transcranial Magnetic Stimulation in the Rat. AB - High cervical spinal cord injuries lead to permanent respiratory deficits. One preclinical model of respiratory insufficiency in adult rats is the C2 partial injury which causes unilateral diaphragm paralysis. This model allows the investigation of a particular population of respiratory bulbospinal axons which cross the midline at C3-C6 spinal segment, namely the crossed phrenic pathway. Transcranial magnetic stimulation (TMS) is a non-invasive technique that can be used to study supraspinal descending respiratory pathways in the rat. Interestingly, a lateral C2 injury does not affect the amplitude and latency of the largest motor-evoked potential recorded from the diaphragm (MEPdia) ipsilateral to the injury in response to a single TMS pulse, compared to a sham animal. Although the rhythmic respiratory activity on the contralateral diaphragm is preserved at 7 days post-injury, no diaphragm activity can be recorded on the injured side. However, a profound reorganization of the MEPdia evoked by TMS can be observed. The MEPdia is reduced on the non-injured rather than the injured side. This suggests an increase in ipsilateral phrenic motoneurons excitability. Moreover, correlations between MEPdia amplitude and spontaneous contralateral diaphragmatic activity were observed. The larger diaphragm activity correlated with a larger MEPdia on the injured side, and a smaller MEPdia on the non-injured side. This suggests, for the first time, the occurrence of a functional neuroplasticity process involving changes in motoneuron excitability balance between the injured and non-injured sides at a short post-lesional delay. PMID- 26828651 TI - Comparing Simultaneous and Pointwise Confidence Intervals for Hydrological Processes. AB - Distribution function estimation of the random variable of river flow is an important problem in hydrology. This issue is directly related to quantile estimation, and consequently to return level prediction. The estimation process can be complemented with the construction of confidence intervals (CIs) to perform a probabilistic assessment of the different variables and/or estimated functions. In this work, several methods for constructing CIs using bootstrap techniques, and parametric and nonparametric procedures in the estimation process are studied and compared. In the case that the target is the joint estimation of a vector of values, some new corrections to obtain joint coverage probabilities closer to the corresponding nominal values are also presented. A comprehensive simulation study compares the different approaches, and the application of the different procedures to real data sets from four rivers in the United States and one in Spain complete the paper. PMID- 26828649 TI - Effects of Incretin-Based Therapies on Neuro-Cardiovascular Dynamic Changes Induced by High Fat Diet in Rats. AB - BACKGROUND AND AIMS: Obesity promotes cardiac and cerebral microcirculatory dysfunction that could be improved by incretin-based therapies. However, the effects of this class of compounds on neuro-cardiovascular system damage induced by high fat diet remain unclear. The aim of this study was to investigate the effects of incretin-based therapies on neuro-cardiovascular dysfunction induced by high fat diet in Wistar rats. METHODS AND RESULTS: We have evaluated fasting glucose levels and insulin resistance, heart rate variability quantified on time and frequency domains, cerebral microcirculation by intravital microscopy, mean arterial blood pressure, ventricular function and mitochondrial swelling. High fat diet worsened biometric and metabolic parameters and promoted deleterious effects on autonomic, myocardial and haemodynamic parameters, decreased capillary diameters and increased functional capillary density in the brain. Biometric and metabolic parameters were better improved by glucagon like peptide-1 (GLP-1) compared with dipeptdyl peptidase-4 (DPP-4) inhibitor. On the other hand, both GLP-1 agonist and DPP-4 inhibitor reversed the deleterious effects of high fat diet on autonomic, myocardial, haemodynamic and cerebral microvascular parameters. GLP-1 agonist and DPP-4 inhibitor therapy also increased mitochondrial permeability transition pore resistance in brain and heart tissues of rats subjected to high fat diet. CONCLUSION: Incretin-based therapies improve deleterious cardiovascular effects induced by high fat diet and may have important contributions on the interplay between neuro-cardiovascular dynamic controls through mitochondrial dysfunction associated to metabolic disorders. PMID- 26828650 TI - Kernel Architecture of the Genetic Circuitry of the Arabidopsis Circadian System. AB - A wide range of organisms features molecular machines, circadian clocks, which generate endogenous oscillations with ~24 h periodicity and thereby synchronize biological processes to diurnal environmental fluctuations. Recently, it has become clear that plants harbor more complex gene regulatory circuits within the core circadian clocks than other organisms, inspiring a fundamental question: are all these regulatory interactions between clock genes equally crucial for the establishment and maintenance of circadian rhythms? Our mechanistic simulation for Arabidopsis thaliana demonstrates that at least half of the total regulatory interactions must be present to express the circadian molecular profiles observed in wild-type plants. A set of those essential interactions is called herein a kernel of the circadian system. The kernel structure unbiasedly reveals four interlocked negative feedback loops contributing to circadian rhythms, and three feedback loops among them drive the autonomous oscillation itself. Strikingly, the kernel structure, as well as the whole clock circuitry, is overwhelmingly composed of inhibitory, rather than activating, interactions between genes. We found that this tendency underlies plant circadian molecular profiles which often exhibit sharply-shaped, cuspidate waveforms. Through the generation of these cuspidate profiles, inhibitory interactions may facilitate the global coordination of temporally-distant clock events that are markedly peaked at very specific times of day. Our systematic approach resulting in experimentally testable predictions provides insights into a design principle of biological clockwork, with implications for synthetic biology. PMID- 26828652 TI - High-Fat Diet Changes Hippocampal Apolipoprotein E (ApoE) in a Genotype- and Carbohydrate-Dependent Manner in Mice. AB - Alzheimer's disease is a currently incurable neurodegenerative disease affecting millions of individuals worldwide. Risk factors for Alzheimer's disease include genetic risk factors, such as possession of epsilon4 allele of apolipoprotein E (ApoE4) over the risk-neutral ApoE3 allele, and lifestyle risk factors, such as diet and exercise. The intersection of these two sources of disease risk is not well understood. We investigated the impact of diet on ApoE levels by feeding wildtype, ApoE3, and ApoE4 targeted replacement (TR) mice with chow, high-fat, or ketogenic (high-fat, very-low-carbohydrate) diets. We found that high-fat diet affected both plasma and hippocampal levels of ApoE in an isoform-dependent manner, with high-fat diet causing a surprising reduction of hippocampal ApoE levels in ApoE3 TR mice. Conversely, the ketogenic diet had no effect on hippocampal ApoE. Our findings suggest that the use of dietary interventions to slow the progression AD should take ApoE genotype into consideration. PMID- 26828653 TI - Genomic Alteration During Metastasis of Lung Adenocarcinoma. AB - BACKGROUND/AIMS: Recurrent gene mutation has been identified by the analysis of exonic DNA from lung adenocarcinoma, but its progression has not been extensively profiled. The investigation of the mutational landscape of tumors provides new insights into cancer genome evolution and further discovers the interplay of somatic mutation, adaptation of clones to their environment and natural selection. Cancer development involves cycles of genomic damage, epigenetic deregulation, and increased cellular proliferation that eventually culminate in the carcinoma phenotype. METHODS: Comparative whole exome sequencing of both primary and metastatic tumor tissues from four patients of stage IV lung adenocarcinoma patients with chest wall metastasis was performed. Both primary and metastatic tumors were diagnosed through biopsy followed by surgical resection. All tumor specimens were cut into several pieces to assess potential heterogenic clones within the tumor tissue. Adjacent normal lung tissue was also obtained to provide germline mutation background. RESULTS: By modeling and analyzing progression of the cancer metastasis based on non-synonymous variants, we defined the extent of heterogeneity of cancer genomes and identified similar cancer evolution pattern in the four patients: metastasis was an early event occurring right after the primary cancer formation and evolution in the metastatic tumor was continuously and simultaneously in progression with that in the primary tumor. By characterizing the clonal hierarchy of genetic lesions, we further charted a pathway of oncogenic events along which genes may drive lung adenocarcinoma metastasis, such as TAS2R31 and UMODL1, involving in G-protein coupled receptor protein signaling pathway. CONCLUSION: The candidate genes identified in this study may become targets for the treatment of lung adenocarcinoma metastasis. PMID- 26828655 TI - BASIC UNPREDICTABILITY OF INDIVIDUAL RESPONSES TO DISCRETE STIMULUS PRESENTATIONS. AB - A common assertion of psychologists is that the objeotive of psychology .is to predict and control behavior. The assertion springs from the belief that psychologists will learn enough about general stimulus-raponse laws and underlying factors' of behavior to predict how a given individual will react in a given discrete stim- ulus situation, and we will be able to arrange situations in a fashion that will control what the individual does. PMID- 26828656 TI - GENERALITY AND RELIABILITY OF INDIVIDUAL SITUATIONS DIFFERENCES IN DISCRETE STIMULUS-ITEM. AB - The basic data with which psychologists commonly deal are the dichotomous responses of individuals t o stimulus presentations. The stimulus situations studied range from those presented in psychophysical brass instrument experiments .to items printed in tests of ability and personality. PMID- 26828658 TI - AN ANALYSIS OF SITUATIONAL DIMENSIONS: A REPLICATION. AB - An analysis of individuals' perceptions of situations was performed and confirmed the main results obtained in an earlier study by Magnusson (1971). Ss gave similarity ratings of situakions from a specific domain. A dimensional analysis and a categorization were mad on data. The method showed good agreement. Stability over time in factor structure was high as well as the agreement between individual structures. The analyses gave a clear and subjectively meaningful structure for both individual data and group data. PMID- 26828657 TI - RESPONSE BIASES AND TRAIT DESCRIPTIVE ADJECTIVES. AB - Twenty subject response parameters, including scales to measure re- sponse reliability, content and acquiescence variance, social desirability, yea- and nay saying, and extremeness response style were obtained for 88 college students, based on 89 pairs of adjecCives oppoSrite both in content and in social desirability. Test-retest item reversal methodology was used to evaluate the possible effects of these biases on responses to the trait-descriptive adjectives. Individual differences in response bias propensities were studied among the various subject response parameters, and in relation to scale scores from the 16 PF, MMPI, and CPI. The results supported a content rather than bias interpretation of the subjects' selfdescriptions for the adjectives. Additionally, no useful associations were found between measures of personality characteristics and response biases. PMID- 26828654 TI - Analysis of Genes Involved in Body Weight Regulation by Targeted Re-Sequencing. AB - INTRODUCTION: Genes involved in body weight regulation that were previously investigated in genome-wide association studies (GWAS) and in animal models were target-enriched followed by massive parallel next generation sequencing. METHODS: We enriched and re-sequenced continuous genomic regions comprising FTO, MC4R, TMEM18, SDCCAG8, TKNS, MSRA and TBC1D1 in a screening sample of 196 extremely obese children and adolescents with age and sex specific body mass index (BMI) >= 99th percentile and 176 lean adults (BMI <= 15th percentile). 22 variants were confirmed by Sanger sequencing. Genotyping was performed in up to 705 independent obesity trios (extremely obese child and both parents), 243 extremely obese cases and 261 lean adults. RESULTS AND CONCLUSION: We detected 20 different non synonymous variants, one frame shift and one nonsense mutation in the 7 continuous genomic regions in study groups of different weight extremes. For SNP Arg695Cys (rs58983546) in TBC1D1 we detected nominal association with obesity (pTDT = 0.03 in 705 trios). Eleven of the variants were rare, thus were only detected heterozygously in up to ten individual(s) of the complete screening sample of 372 individuals. Two of them (in FTO and MSRA) were found in lean individuals, nine in extremely obese. In silico analyses of the 11 variants did not reveal functional implications for the mutations. Concordant with our hypothesis we detected a rare variant that potentially leads to loss of FTO function in a lean individual. For TBC1D1, in contrary to our hypothesis, the loss of function variant (Arg443Stop) was found in an obese individual. Functional in vitro studies are warranted. PMID- 26828659 TI - A COMPARISON OF THE PREDICTIVE ACCURACY OF A POOLING AND A SUBGROUPING PREDICTION STRATEGY. AB - The subgrouping strategy has been employed in a number of studies (Fredriksen & Gilbert, 1960; Fredriksen & Melville, 1964; Ghiselli, 1956; Klein, Rock & Evans, 1968; Rock, Evans & Klein, 1969; Malnig, 1969). In each of these studies it was shown that after partitioning a sample into g subgroups and performing a separate regression analysis within each group, one could identify one or more subgroups having a larger multiple correlation than the total sample regression. An important question is whether this type of result will be maintained under cross validation. PMID- 26828660 TI - A METHOD FOR MAXIMIZING THE RATIO OF TWO QUADRATIC FORMS. AB - A method for solving for the largest eigenvalue and associated eigenvector of the eigenequation (A - XB)s = 0 is presented. The method is contrasted with other procedures for the same problem. PMID- 26828661 TI - VARIMAX AND MAXPLANE ROTATIONAL METHODS UNDER DIFFERENT CONDITIONS OF SAMPLING ERROR AND HIERARCHICAL STRUCTURE. AB - The importance of hierarchical factor structure is well recognized in the analysis of both personality and ability factors. The notion of hierarchical factor structure arises logically from the fact that group factors may be almost infinitely subdivisible. Thus a complete factor analysis of a correlation matrix often will imply an hierarchical factor structure, with relatively specific factors descending from more general ones. The common methods for determining hierarchical s.tructure require the original factor solution to be rotated to oblique, rather than to orthogonal, simple structure. Yet the use of oblique factor rotation poses well-known problems. Relaxing the requirement of orthogonality may allow factor axes to be unduly influenced by chance variation, resulting in spuriously high factor loadings. Further, analytical methods for the oblique case, unlike analytical methods for the orthogonal case, are still in a developmental stage. Thus the bulk of currenk factor studies rely on Varimax rotation and emerge with orthogonal fac- tors, and the possibility of hierarchical factor ordering is little explored. PMID- 26828662 TI - PROCEDURES FOR WEIGHTING FACTORS AND VARIABLES IN ORTHOGONAL CONFIRMATORY FACTOR ANALYSIS. AB - Much has been written on the subject of orthogonal confirma- tory factor analysis since Green's (1952) paper-the first dealing with this problem. Using the procrustean or residual least- squares criterion (to be minimized) of the sum of squared discrep- ancies between elements of the target or hypothesis matrix and those of the best fit, Fischer and Roppert (1964) and Kristof (1964) presented solutions essentially the same as Green's, although Green's solution required both the target and the matrix being transformed to be of full column rank. Schonemann's (1966) solution was most general in that it allowed both of these matrices to be of less than full rank. C1iff (1966) arrived at a slightly less general solution than Schonemann's, but one that was, for practical purposes, identical, although Cliff's criterion (to be maximimized) was different, and not least-squares. Cliff's solution, never- theless, satisfied the least-squares criterion. Gibson (1960, 1962) and Johnson (1966) addressed the related problem of obtaining least-squares orthonormalnizations of oblique transformation matrices. Techniques for rotating a given matrix orthogonally to a least-squares fit to an only partially specified target were outlined by Lawley and Maxwell (1964) and Browne (1970). PMID- 26828663 TI - STEP-DOWN ANALYSIS AND SIMULTANEOUS CONFIDENCE INTERVALS IN MANOVA. AB - Two fundamental ways of analyzing a multivariate analysis of variance (MANOVA) problem in more detail are the stepdown analysis (Roy, 1958; Bock, 1963), and the use of simultaneous confidence intervals (Gabriel, 1968; Morrison, 1967). Assuming a global test of significance, such as Wilk's A, has indicated non- ohance association between the independent variable and the set of dependent variables (this paper will limit discussion to the one- way design), the aforementioned methods may be used to deter- mine which of the dependent variables and/or groups are responsible for the global significance. PMID- 26828664 TI - TLR2, TLR4 and Dectin-1 signalling in hematopoietic stem and progenitor cells determines the antifungal phenotype of the macrophages they produce. AB - TLRs represent an attractive target for the stimulation of myeloid cell production by HSPCs. We have previously demonstrated that HSPCs use TLR2 to sense Candida albicans in vivo and induce the production of macrophages. In this work, we used an in vitro model of HSPCs differentiation to investigate the functional consequences for macrophages of exposure of HSPCs to various PAMPs and C. albicans cells. Mouse HSPCs (Lin(-) cells) were cultured with M-CSF to induce macrophage differentiation, in the presence or absence of the following PRR agonists: Pam3CSK4 (TLR2 ligand), LPS (TLR4 ligand), depleted zymosan (which only activates Dectin-1), or C. albicans yeasts (which activate several PRRs, but principally TLR2 and Dectin-1). Our data show that these PAMPs differentially impact the anti-microbial function of the macrophages produced by the exposed HSPCs. Pure TLR2 and TLR4 ligands generate macrophages with a diminished ability to produce inflammatory cytokines. In contrast, HSPCs activation in response to C. albicans leads to the generation of macrophages that are better prepared to deal with the infection, as they produce higher amounts of inflammatory cytokines and have higher fungicidal capacity than control macrophages. Therefore, the tailored manipulation of the differentiation process may help to boost the innate immune response to infection. PMID- 26828665 TI - Biochemical and full genome sequence analyses of clinical Vibrio cholerae isolates in Mexico reveals the presence of novel V. cholerae strains. AB - The first week of September 2013, the National Epidemiological Surveillance System identified two cases of cholera in Mexico City. The cultures of both samples were confirmed as Vibrio cholerae serogroup O1, serotype Ogawa, biotype El Tor. Initial analyses by PFGE and by PCR-amplification of the virulence genes, suggested that both strains were similar, but different from those previously reported in Mexico. The following week, four more cases were identified in a community in the state of Hidalgo, located 121 km northeast of Mexico City. Thereafter a cholera outbreak started in the region of La Huasteca. Genomic analyses of the four strains obtained in this study confirmed the presence of Pathogenicity Islands VPI-1 and -2, VSP-1 and -2, and of the integrative element SXT. The genomic structure of the 4 isolates was similar to that of V. cholerae strain 2010 EL-1786, identified during the epidemic in Haiti in 2010. PMID- 26828666 TI - Morphological Symmetry of Maxillary Anterior Teeth before and after Prosthodontic Planning: Comparison between Conventional and Digital Diagnostic Wax-Ups. AB - OBJECTIVE: The aim of this study was to evaluate the impact of different prosthodontic planning methods on the morphological symmetry of maxillary anterior teeth. MATERIALS AND METHODS: In 13 patients receiving fixed prosthodontic treatment, dental models were obtained from the Oral Health Centre of Western Australia. Two forms of diagnostic prosthodontic planning were executed: conventional wax-up and digital wax-up. The asymmetry was evaluated at two levels: tooth morphological asymmetry (TMA) and anterior segment morphological asymmetry (ASMA). For the TMA, the labial surface of each anterior tooth was superimposed on a mirror image of the contralateral tooth. The ASMA involved superimposition of the combined labial surface of all the anterior teeth on one side on the mirror image of the combined labial surface of the contralateral side. For each asymmetry, the discrepancies in the form of 3D Euclidean distances were calculated and statistically evaluated by the Kruskal Wallis test (p = 0.05). RESULTS: At the TMA level, the digital wax-up models had significantly less asymmetry (p < 0.00) than the pre-treatment and conventional wax-up models. The pre-treatment and conventional wax-up models had similar asymmetry (p = 0.35). However, at the ASMA level, the difference between the models was insignificant (p > 0.05). CONCLUSION: In this study, the single tooth symmetry had improved after the digital wax-up. However, the conventional wax-up had a minimal impact on single tooth symmetry. ASMA was minimally affected by the two wax-ups. PMID- 26828667 TI - SOCS3 is epigenetically up-regulated in steroid resistant nephrotic children. AB - BACKGROUND: The mechanism of steroid resistance in children with the nephrotic syndrome is yet unknown. About 20% of patients demonstrate steroid unresponsiveness and progress to end stage renal disease. Aberrant SOCS3 and SOCS5 expression in steroid resistant and sensitive patients has previously been demonstrated. Here, we investigate genetic and epigenetic mechanisms of regulation of SOCS3 and SOCS5 transcription in nephrotic children. METHODS: 76 patients with the nephrotic syndrome (40 steroid resistant and 36 steroid sensitive) and 33 matched controls were included in this study. We performed genotyping of a total of 34 single nucleotide polymorphisms for SOCS3 and SOCS5 promoters and evaluated their methylation status using MS-PCR and QMSP methods. RESULTS: Steroid resistant patients had a significantly lower methylation of one region of SOCS3 promoter in comparison with steroid sensitive patients and controls (p < 0.0001). However, the relative methylation level in the steroid sensitive patients and controls differed significantly even before the first steroid dose (p = 0.001758). Other SOCS3 and SOCS5 promoter regions displayed no differences in methylation or were fully methylated/unmethylated in all study groups, showing site-specific methylation. The allele and genotype distribution for SOCS3 and SOCS5 markers did not differ statistically between the groups. CONCLUSIONS: We demonstrate an epigenetic mechanism of SOCS3 up-regulation in steroid resistant children with the nephrotic syndrome. The assessment of methylation/unmethylation of SOCS3 promoter might be an early marker for steroid responsiveness in NS patients. PMID- 26828668 TI - Coma in the course of severe poisoning after consumption of red fly agaric (Amanita muscaria). AB - Red fly agaric poisoning is rare. It can be consumed for suicidal purposes or its psychedelic effect. The paper describes the case of a young men, who fell into a coma after ingestion of the red toadstools. Quick identification of the poison, early use of gastric lavage and symptomatic treatment resulted in regression of symptoms and lead to the patient's discharge from the hospital on the third day after intoxication. Authors discussing the poisonous alkaloids contained in the red toadtools: ibotenic acid, muscimol, muscasone and muscarine and theirs properties, responsible for the symptoms of intoxication. PMID- 26828669 TI - Abscisic acid - an overlooked player in plant-microbe symbioses formation? AB - Abscisic acid (ABA) is an ubiquitous plant hormone and one of the foremost signalling molecules, controlling plants' growth and development, as well as their response to environmental stresses. To date, the function of ABA has been extensively investigated as an abiotic stress molecule which regulates the plants' water status. However, in the context of symbiotic associations, ABA is less recognized. In contrast to well-described auxin/cytokinin and gibberellin/strigolactone involvement in symbioses, ABA has long been underestimated. Interestingly, ABA emerges as an important player in arbuscular mycorrhiza and legume-rhizobium symbiosis. The plant's use of stress hormones like ABA in regulation of those interactions directly links the efficiency of these processes to the environmental status of the plant, notably during drought stress. Here we provide an overview of ABA interplay in beneficial associations of plants with microorganisms and propose ABA as a potential factor determining whether the investment in establishing the interaction is higher than the profit coming from it. PMID- 26828670 TI - Synthesis of a bi-functional dendrimer-based nanovehicle co-modified with RGDyC and TAT peptides for neovascular targeting and penetration. AB - The dual-ligand dendritic polyamidoamine-(polyethylene glycol)n-cyclic RGDyC peptide-(TAT peptide) (PPnR(T)) with various supplied molar ratios of polyethylene glycol (PEG) to polyamidoamine (PAMAM) (n=5, 15, 30) were designed as drug-carriers for the treatment of neovascular diseases; their targeting and penetrating effects were subsequently evaluated. (1)H NMR demonstrated PPnR(T) was successfully synthesized. Compared with the unmodified PAMAM, in vitro cytotoxicity of PPnR(T) to alphavbeta3 negative cells (alphavbeta3-) was significantly reduced, whereas the lethality to pathologic neovascular endothelial cells (alphavbeta3+) was efficiently increased compared to PPn. Compared to PP5R(T) and PP15R(T), PP30R(T) exhibited the most selective and efficient cellular uptake by human umbilical vein endothelial cells (HUVECs, alphavbeta3+). Membrane interaction study indicated the cellular uptake process of PP30R(T) of HUVECs mainly involved specific RGD-alphavbeta3 recognition as well as electrostatic interactions. Intracellular localization results confirmed PP30R(T) was distributed in the cytoplasm in HUVECs. 3D tumor spheroids penetration studies demonstrated that PP30R(T) penetrated the A549 cells to reach the depths of the avascular tumor spheroids. In vivo imaging further demonstrated that PP30R(T) achieved profoundly improved distribution in tumor tissues where angiogenesis existed. Therefore, the bi-functional dendrimer PP30R(T) displayed great potential as a nano-carrier for targeted drug delivery both in vitro and in vivo, and had broad prospects as nanocarriers for the targeted treatment of neovascular diseases. PMID- 26828671 TI - Self-assembled nano-architecture liquid crystalline particles as a promising carrier for progesterone transdermal delivery. AB - The study aims to elaborate novel self-assembled liquid crystalline nanoparticles (LCNPs) for management of hormonal disturbances following non-invasive progesterone transdermal delivery. Fabrication and optimization of progesteroneloaded LCNPs for transdermal delivery were assessed via a quality by design approach based on 2(3) full factorial design. The design includes the functional relationships between independent processing variables and dependent responses of particle size, polydispersity index, zeta potential, cumulative drug released after 24h and ex-vivo transdermal steady flux. The developed nanocarrier was subjected to TEM (transmission electron microscope) for morphological elucidation and stability study within a period of three months at different storage temperatures. The cubic phase of LCNPs was successfully prepared using glyceryl monooleate (GMO) via the emulsification technique. Based on the factorial design, the independent operating variables significantly affected the five dependent responses. The cubosomes hydrodynamic diameters were in the nanometric range (101-386 nm) with narrow particle size distribution, high negative zeta potential >=-30 mV and entrapment efficiency >=94%. The LCNPs succeeded in sustaining progesterone release for almost 24h, following a non fickian transport of drug diffusion mechanism. Ex-vivo study revealed a significant enhancement up to 6 folds in the transdermal permeation of progesterone-loaded LCNPs compared to its aqueous suspension. The optimized LCNPs exhibited a high physical stability while retaining the cubic structure for at least three months. Quality by design approach successfully accomplished a predictable mathematical model permitting the development of novel LCNPs for transdermal delivery of progesterone with the benefit of reducing its oral route side effects. PMID- 26828672 TI - Nanoparticle cross-linked collagen shields for sustained delivery of pilocarpine hydrochloride. AB - Glaucoma is a common progressive eye disorder which remains the second leading cause of blindness worldwide. Current therapy involves frequent administration of eye drops which often results in poor patient adherence and therapeutic outcomes. The aim of this study was to overcome these limitations by developing a novel nanoparticle cross-linked collagen shield for sustained delivery of pilocarpine hydrochloride (PHCl). Three metal oxide nanoparticles (NPs); titanium dioxide (TiO2), zinc oxide (ZnO) and polyvinylpyrrolidone (PVP) capped zinc oxide (ZnO/PVP), were evaluated for their cytotoxicity as well as shield transparency before selecting ZnO/PVP NPs as the ideal candidate. Cross-linked collagen shields were then characterized for their mechanical strength, swelling capacity and bioadhesive properties, with ZnO/PVP NP cross-linked shields showing the most favorable characteristics compared to plain films. The shield with the best properties was then loaded with PHCl and in vitro release of zinc ions as well as PHCl was measured without and with further cross-linking by ultraviolet irradiation. The concentration of zinc ions released was well below the IC50 rendering them safe for ocular use. Moreover, collagen shields cross-linked with ZnO/PVP NPs released PHCl over a period of 14 days offering a promising sustained release treatment option for glaucoma. PMID- 26828673 TI - Interdigitation Zone Band Restoration After Treatment of Diabetic Macular Edema. AB - PURPOSE: To investigate whether the integrity of the interdigitation zone band, the ellipsoid zone band, and the external limiting membrane are reliable markers of treatment outcome in diabetic macular edema (DME). METHODS: In this retrospective study, we examined 41 treatment-naive eyes (38 patients) with DME that were treated with laser therapy, pharmacotherapy, and/or vitrectomy. Best corrected visual acuity and the integrity of the interdigitation zone band, the ellipsoid zone band, and the external limiting membrane were assessed before treatment and at 3, 6, and 12 months after DME treatment. RESULTS: One year after treatment, the external limiting membrane, ellipsoid zone band, and interdigitation zone band were completely visible in 30 (73.2%), 24 (58.5%), and 2 (4.9%) eyes, respectively. Interdigitation zone band status improved significantly (P = 0.005) 1 year after treatment. The interdigitation zone did not improve in the absence of the ellipsoid zone band. Likewise, ellipsoid zone status did not improve in the absence of the external limiting membrane at any time after treatment. CONCLUSION: The results of this study show that restoration of the interdigitation zone band constitutes a very sensitive marker of DME treatment outcome when the ellipsoid zone band is visible before treatment. PMID- 26828674 TI - Three new 2,5-diketopiperazines from the fish intestinal Streptomyces sp. MNU FJ 36. AB - The gut actinobacteria of marine-inhabited fish is one of the most important reservoirs of novel natural products. Currently, the Streptomyces sp. MNU FJ-36 was isolated from the intestinal fabric of Katsuwonus sp. and determined by 16S rRNA analysis. From the cultures of the S. sp. MNU FJ-36, three new 2,5 diketopiperazines (2,5-DKPs) were discovered and identified as 3-(3-hydroxy-4 methoxybenzyl)-6-isobutyl-2,5-diketopiperazine (1), 3-(1,3-benzodioxol-5 ylmethyl)-6-isobutyl-2,5-diketopiperazine (2) and 3-(1,3-benzodioxol-5-ylmethyl) 6-isopropyl-2,5-diketopiperazine (3). Their structures were elucidated on the basis of spectroscopic data analysis. All the compounds were also evaluated for their inhibitory activity against P388, A-549 and HCT-116 cell lines with the MTT assay. PMID- 26828675 TI - The Functional Unit of Neisseria meningitidis 3-Deoxy-?-Arabino-Heptulosonate 7 Phosphate Synthase Is Dimeric. AB - Neisseria meningitidis 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (NmeDAH7PS) adopts a homotetrameric structure consisting of an extensive and a less extensive interface. Perturbation of the less extensive interface through a single mutation of a salt bridge (Arg126-Glu27) formed at the tetramer interface of all chains resulted in a dimeric DAH7PS in solution, as determined by small angle X-ray scattering, analytical ultracentrifugation and analytical size exclusion chromatography. The dimeric NmeDAH7PSR126S variant was shown to be catalytically active in the aldol-like condensation reaction between D-erythrose 4-phosphate and phosphoenolpyruvate, and allosterically inhibited by L phenylalanine to the same extent as the wild-type enzyme. The dimeric NmeDAH7PSR126S variant exhibited a slight reduction in thermal stability by differential scanning calorimetry experiments and a slow loss of activity over time compared to the wild-type enzyme. Although NmeDAH7PSR126S crystallised as a tetramer, like the wild-type enzyme, structural asymmetry at the less extensive interface was observed consistent with its destabilisation. The tetrameric association enabled by this Arg126-Glu27 salt-bridge appears to contribute solely to the stability of the protein, ultimately revealing that the functional unit of NmeDAH7PS is dimeric. PMID- 26828676 TI - Expression Profile of microRNAs and Their Targeted Pathways in Human Ovaries Detected by Next-Generation Small RNA Sequencing. AB - Recently, post-transcriptional gene regulation by microRNAs (miRNAs) has been reported to play a key role during ovary development and differentiation. However, there are no published studies identifying miRNA profiles of human ovarian tissues directly using next-generation sequencing technology. In the human ovary, a total of 762 known and 21 novel human miRNAs were detected, indicating that human ovaries have a complex population of small RNAs. To confirm the miRNA profile in human ovaries, quantitative real-time polymerase chain reaction was used to validate the expression of known miRNAs and novel miRNAs. The potential regulating roles of miRNA in physiological function of ovaries were analyzed by gene ontology and Kyoto encyclopedia of genes and genomes pathway annotation, and several important processes were identified to be targeted by the most abundantly expressed miRNAs, for example, antral ovarian follicle growth, ovarian follicle rupture, and fertilization. Our current findings extend the knowledge of the regulatory role of miRNAs and their targeted processes in human ovaries, suggesting that miRNAs play important roles in development and physiological function of ovaries. In this study, we provide a useful resource for further research of the regulatory role of miRNAs in the ovaries, which may also provide novel candidates for molecular biomarkers or treatment targets in the research of female infertility. PMID- 26828677 TI - Impact of an educational program on knowledge and practice of health care staff toward pharmaceutical waste management in Gaza, Palestine. AB - In health care facilities, pharmaceutical waste is generally discharged down the drain or sent to landfill. Poor knowledge about their potential downstream impacts may be a primary factor for improper disposal behavior. The objective of this study was to determine the impact of an intervention program on knowledge and practice of health care staff regarding pharmaceutical waste management. The study was designed as a pre/posttest intervention study. Total sample size was 530 in the pre-intervention phase, and then a subsample of 69 individuals was selected for the intervention and the post-intervention phases. Paired-sample t test was used to assess the difference between pretest and follow-up test results. A statistically significant improvement in knowledge and practice was achieved (P<0.001). Poor knowledge and poor practice levels (scores<50%) were found to improve to satisfactory levels (scores>=75%). Therefore, educational programs could be considered as an effective tool for changing health care staff practice in pharmaceutical waste management. IMPLICATIONS: In health care facilities, pharmaceutical waste is generally discharged down the drain or sent to landfill. A lack of knowledge about the potential impacts of this type of waste may be a leading factor in improper disposal behavior. Following an educational program, statistically significant improvement in knowledge and practice of health care staff as regards to pharmaceutical waste management (PWM) was achieved. It is thus recommended that authorities implement training-of trainers (TOT) programs to educate health care staff on PWM and organize refreshment workshops regularly. PMID- 26828678 TI - Effects of ovariectomy on periodontal tissues following tooth replantation. AB - OBJECTIVES: The aim of the study was to analyze the effects of ovariectomy on periodontal tissues following immediate tooth replantation by histomorphometric, immunohistochemistry, and MUCT analysis. MATERIALS AND METHODS: Eighty wistar rats (Rattus norvegicus albinos) with normal estrous cycles were randomly divided into two groups: ovariectomized (OVX) and Sham. Two months after surgery, the rats' upper right incisor was extracted followed by immediate reimplantation. The animals were sacrificed after 28, 45, and 60 days healing time. Histomorphometric and immunohistochemical analysis were performed by evaluation of PCNA and TRAP straining. RESULTS: The periodontal ligament was reinserted into the bone and cementum in the both groups. The immunohistochemical analysis revealed PCNA positive cells on the periodontal ligament in both groups at 28 days. Root resorption was noted at 45 days with immunoreactive cells for TRAP present in bone and tooth surface however no statistical differences between the groups were noticed. Histomorphometric analysis showed significant difference between groups in the periodontal ligament and root resorption parameters for the sub-items: intensity of chronic inflammatory infiltrate at 60 days (p<0.01), the organization of the periodontal ligament at 28 days (p<0.05), depth of root resorption at 45 days (p<0.05) and at 60 days (p<0.001). The MUCT analysis showed multiple areas of bone resorption in association with OVX at 28 and 60 days with no significant differences between times in vivo. CONCLUSION: The ovariectomy did not have significant influence in periodontal tissue parameters following tooth reimplantation. PMID- 26828679 TI - Early tissue reaction in the tension zone of PDL during orthodontic tooth movement. AB - OBJECTIVE: The aim of the study was to examine the early tissue reaction in the tension zone of periodontal ligament (PDL) during orthodontic tooth movement. DESIGN: Upper first molars of rats were moved buccally with fixed appliances. The PDL in the tension zone was examined histologically, immunohistochemically and at a molecular level after 24h, 3 days and 7 days. RESULTS: After 24h of orthodontic force loading, the periodontal space appeared considerably expanded. The periodontal fibers were stretched between the bone and the root. Three days after loading, the expanded periodontal space had slightly narrowed, the periodontal fiber arrangement was relaxed, and the blood vessels did not appear elongated. A considerable layer of osteoid was formed on the bone surface. The total cross sectional areas of the PDL in experimental groups were significantly larger than control group. The total cross-sectional areas of the blood vessels were not significantly different among the groups. Significantly high expressions of IL 1beta and PTX3 were characteristically observed not only in the endothelial cells and cells around the blood vessel, but also in fibroblasts throughout the PDL of the tension zone 24h after orthodontic force loading. Three and 7 days after loading, these showed tendencies to return to control levels. CONCLUSIONS: The present results suggest that the early reaction in the tension zone of the PDL during tooth movement consists of two phases: first, inflammation and second, rapid recovery and renovation of the PDL with bone formation. PMID- 26828680 TI - Combination strategy of multi-layered surface camouflage using hyperbranched polyethylene glycol and immunosuppressive drugs for the prevention of immune reactions against transplanted porcine islets. AB - This study suggests a novel method of stabilizing fragile porcine islets to prevent the dissociation after isolation and reducing immune cell invasion in a combination therapy of 'surface camouflaging' and immunosuppressive drugs (FK506, Rapamycin, MR-1, anti-CD19 mAb, and Clodrosome((r))) to effectively alleviate overall immune reactions against xenotransplanted porcine islets. The surface camouflage of pancreatic islets using biocompatible materials improved stabilization of pancreatic islet and prevented the infiltration of immune cells. Firstly, the surface of porcine islets was camouflaged by SH-6-arm-PEG-lipid and gelatin-catechol (artificial extracellular matrix) in order to stabilize the fragile isolated islets. Secondly, three different PEG layers (6-arm-PEG-SH, 6 arm-PEG-catechol, and linear PEG-SH) were chemically conjugated onto the surface of the stabilized porcine islets. Both artificial extracellular matrix (artificial ECM) and PEGylation effectively covered the surface of porcine islets without increasing the size of the whole islet. In addition, the viability and functionality of the islets were not affected by this multi-layer surface modification. The multi-layer modification significantly reduced the attachment of human serum albumin, fibronectin, and immunoglobulin G in comparison to the control collagen surface. The combination effect of multi-layer PEGylation and cocktailed immunosuppressive drugs on the survival time of the transplanted islets was assessed in a xenogeneic porcine-to-mouse model. The median survival time (MST) of 'artificial ECM + PEGylation' group was 4-fold increased compared to that of control group. In addition, the MST of 'artificial ECM + PEGylation + drug' group was 2.16-fold increased, compared to the 'control + drug' group. In conclusion, we proposed a novel porcine islet transplantation protocol using surface multi-layer modification and cocktailed immunosuppressive drugs, for stabilization and immunoprotection against xenogeneic immune reactions. PMID- 26828682 TI - Guided bone regeneration is promoted by the molecular events in the membrane compartment. AB - The working hypothesis of guided bone regeneration (GBR) is that the membrane physically excludes non-osteogenic tissues from interfering with bone healing. However, the underlying mechanisms are insufficiently explained. This study aimed to investigate the molecular and structural pattern of bone healing in trabecular bone defects, with and without naturally derived resorbable membrane. Defects were created in rat femurs and treated with the membrane or left empty (sham). After 3d, 6d and 28d, the defect sites and membranes were harvested and analyzed with histology, histomorphometry, quantitative-polymerase chain reaction (qPCR), Western blot (WB) and immunohistochemistry (IHC). Histomorphometry demonstrated that the presence of the membrane promoted bone formation in early and late periods. This was in parallel with upregulation of cell recruitment and coupled bone remodeling genes in the defect. Cells recruited into the membrane expressed signals for bone regeneration (BMP-2, FGF-2, TGF-beta1 and VEGF). Whereas the native membrane contained FGF-2 but not BMP-2, an accumulation of FGF-2 and BMP-2 proteins and immunoreactive cells were demonstrated by WB and IHC in the in vivo implanted membrane. The results provide cellular and molecular evidence suggesting a novel role for the membrane during GBR, by acting as a bioactive compartment rather than a passive barrier. PMID- 26828681 TI - Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain. AB - Strategies to enhance survival and direct the differentiation of stem cells in vivo following transplantation in tissue repair site are critical to realizing the potential of stem cell-based therapies. Here we demonstrated an effective approach to promote neuronal differentiation and maturation of human fetal tissue derived neural stem cells (hNSCs) in a brain lesion site of a rat traumatic brain injury model using biodegradable nanoparticle-mediated transfection method to deliver key transcriptional factor neurogenin-2 to hNSCs when transplanted with a tailored hyaluronic acid (HA) hydrogel, generating larger number of more mature neurons engrafted to the host brain tissue than non-transfected cells. The nanoparticle-mediated transcription activation method together with an HA hydrogel delivery matrix provides a translatable approach for stem cell-based regenerative therapy. PMID- 26828683 TI - Planar and tubular patterning of micro and nano-topographies on poly(vinyl alcohol) hydrogel for improved endothelial cell responses. AB - Poly(vinyl alcohol) hydrogel (PVA) is a widely used material for biomedical devices, yet there is a need to enhance its biological functionality for in vitro and in vivo vascular application. Significance of surface topography in modulating cellular behaviour is increasingly evident. However, hydrogel patterning remains challenging. Using a casting method, planar PVA were patterned with micro-sized features. To achieve higher patterning resolution, nanoimprint lithography with high pressure and temperature was used. In vitro experiment showed enhanced human endothelial cell (EC) density and adhesion on patterned PVA. Additional chemical modification via nitrogen gas plasma on patterned PVA further improved EC density and adhesion. Only EC monolayer grown on plasma modified PVA with 2 MUm gratings and 1.8 MUm concave lens exhibited expression of vascular endothelial cadherin, indicating EC functionality. Patterning of the luminal surface of tubular hydrogels is not widely explored. The study presents the first method for simultaneous tubular molding and luminal surface patterning of hydrogel. PVA graft with 2 MUm gratings showed patency and endothelialization, while unpatterned grafts were occluded after 20 days in rat aorta. The reproducible, high yield and high-fidelity methods enable planar and tubular patterning of PVA and other hydrogels to be used for biomedical applications. PMID- 26828684 TI - Polyurethane scaffold with in situ swelling capacity for nucleus pulposus replacement. AB - Nucleus pulposus (NP) replacement offers a minimally invasive alternative to spinal fusion or total disc replacement for the treatment of intervertebral disc (IVD) degeneration. This study aimed to develop a cytocompatible NP replacement material, which is feasible for non-invasive delivery and tunable design, and allows immediate mechanical restoration of the IVD. A bi-phasic polyurethane scaffold was fabricated consisting of a core material with rapid swelling property and a flexible electrospun envelope. The scaffold was assessed in a bovine whole IVD organ culture model under dynamic load for 14 days. Nucleotomy was achieved by incision through the endplate without damaging the annulus fibrosus. After implantation of the scaffold and in situ swelling, the dynamic compressive stiffness and disc height were restored immediately. The scaffold also showed favorable cytocompatibility for native disc cells. Implantation of the scaffold in a partially nucleotomized IVD down-regulated catabolic gene expression, increased proteoglycan and type II collagen intensity and decreased type I collagen intensity in remaining NP tissue, indicating potential to retard degeneration and preserve the IVD cell phenotype. The scaffold can be delivered in a minimally invasive manner, and the geometry of the scaffold post-hydration is tunable by adjusting the core material, which allows individualized design. PMID- 26828685 TI - Development of a long-acting, protein-loaded, redox-active, injectable gel formed by a polyion complex for local protein therapeutics. AB - Although cancer immunotherapies are attracting much attention, it is difficult to develop bioactive proteins owing to the severe systemic toxicity. To overcome the issue, we designed new local protein delivery system by using a protein-loaded, redox-active, injectable gel (RIG), which is formed by a polyion complex (PIC) comprising three components, viz., cationic polyamine-poly(ethylene glycol) polyamine triblock copolymer possessing ROS-scavenging moieties as side chains; anionic poly(acrylic acid); and a protein. The mixture formed the protein-loaded PIC flower micelles at room temperature, which immediately converted to a gel with high mechanical strength upon exposure to physiological conditions. Because the protein electrostatically interacts with the PIC gel network, RIG provided a sustained release of the protein without a significant initial burst, regardless of the types of proteins in vitro, and much longer retention of the protein at the local injection site in mice than that of the naked protein. Subcutaneous injections of IL-12@RIG in the vicinity of tumor tissue showed remarkable tumor growth inhibition in tumor-bearing mice, compared to that observed with injection of IL-12 alone, suppressing adverse events caused by IL-12-induced ROS. Our results indicate that RIG has potential as a platform technology for an injectable sustained-release carrier for proteins. PMID- 26828686 TI - Amphiphilic macromolecule nanoassemblies suppress smooth muscle cell proliferation and platelet adhesion. AB - While the development of second- and third-generation drug-eluting stents (DES) have significantly improved patient outcomes by reducing smooth muscle cell (SMC) proliferation, DES have also been associated with an increased risk of late-stent thrombosis due to delayed re-endothelialization and hypersensitivity reactions from the drug-polymer coating. Furthermore, DES anti-proliferative agents do not counteract the upstream oxidative stress that triggers the SMC proliferation cascade. In this study, we investigate biocompatible amphiphilic macromolecules (AMs) that address high oxidative lipoprotein microenvironments by competitively binding oxidized lipid receptors and suppressing SMC proliferation with minimal cytotoxicity. To determine the influence of nanoscale assembly on proliferation, micelles and nanoparticles were fabricated from AM unimers containing a phosphonate or carboxylate end-group, a sugar-based hydrophobic domain, and a hydrophilic poly(ethylene glycol) domain. The results indicate that when SMCs are exposed to high levels of oxidized lipid stimuli, nanotherapeutics inhibit lipid uptake, downregulate scavenger receptor expression, and attenuate scavenger receptor gene transcription in SMCs, and thus significantly suppress proliferation. Although both functional end-groups were similarly efficacious, nanoparticles suppressed oxidized lipid uptake and scavenger receptor expression more effectively compared to micelles, indicating the relative importance of formulation characteristics (e.g., higher localized AM concentrations and nanotherapeutic stability) in scavenger receptor binding as compared to AM end group functionality. Furthermore, AM coatings significantly prevented platelet adhesion to metal, demonstrating its potential as an anti-platelet therapy to treat thrombosis. Thus, AM micelles and NPs can effectively repress early stage SMC proliferation and thrombosis through non-cytotoxic mechanisms, highlighting the promise of nanomedicine for next-generation cardiovascular therapeutics. PMID- 26828687 TI - Micellar and structural stability of nanoscale amphiphilic polymers: Implications for anti-atherosclerotic bioactivity. AB - Atherosclerosis, a leading cause of mortality in developed countries, is characterized by the buildup of oxidized low-density lipoprotein (oxLDL) within the vascular intima, unregulated oxLDL uptake by macrophages, and ensuing formation of arterial plaque. Amphiphilic polymers (AMPs) comprised of a branched hydrophobic domain and a hydrophilic poly(ethylene glycol) (PEG) tail have shown promising anti-atherogenic effects through direct inhibition of oxLDL uptake by macrophages. In this study, five AMPs with controlled variations were evaluated for their micellar and structural stability in the presence of serum and lipase, respectively, to develop underlying structure-atheroprotective activity relations. In parallel, molecular dynamics simulations were performed to explore the AMP conformational preferences within an aqueous environment. Notably, AMPs with ether linkages between the hydrophobic arms and sugar backbones demonstrated enhanced degradation stability and storage stability, and also elicited enhanced anti-atherogenic bioactivity. Additionally, AMPs with increased hydrophobicity elicited increased atheroprotective bioactivity in the presence of serum. These studies provide key insights for designing more serum-stable polymeric micelles as prospective cardiovascular nanotherapies. PMID- 26828688 TI - The role of the PI3K/Akt/mTOR pathway in glial scar formation following spinal cord injury. AB - Several studies suggest that glial scars pose as physical and chemical barriers that limit neurite regeneration after spinal cord injury (SCI). Evidences suggest that the activation of the PI3K/Akt/mTOR signaling pathway is involved in glial scar formation. Therefore, inhibition of the PI3K/Akt/mTOR pathway may beneficially attenuate glial scar formation after SCI. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) negatively regulates the PI3K/Akt/mTOR pathway. Therefore, we hypothesized that the overexpression of PTEN in the spinal cord will have beneficial effects after SCI. In the present study, we intrathecally injected a recombinant adenovirus carrying the pten gene (Ad-PTEN) to cause overexpression of PTEN in rats with contusion injured spinal cords. The results suggest overexpression of PTEN in spinal cord attenuated glial scar formation and led to improved locomotor function after SCI. Overexpression of PTEN following SCI attenuated gliosis, affected chondroitin sulfate proteoglycan expression, and improved axon regeneration into the lesion site. Furthermore, we suggest that the activation of the PI3K/Akt/mTOR pathway in astrocytes at 3 days after SCI may be involved in glial scar formation. Because delayed treatment with Ad-PTEN enhanced motor function recovery more significantly than immediate treatment with Ad-PTEN after SCI, the results suggest that the best strategy to attenuate glial scar formation could be to introduce 3 days after SCI. This study's findings thus have positive implications for patients who are unable to receive immediate medical attention after SCI. PMID- 26828689 TI - Intranatal Torsion of Polydactyly: A Rare Event. AB - Polydactyly is one of the most common anomalies of hand and/or foot. Postnatal torsion of pedunculated polydactyly is a well known complication but intranatal torsion has been infrequently described in published literature. Here, we describe a case of pedunculated ulnar polydactyly which was gangrenous at birth due to intranatal torsion. Controversies surrounding the management of narrow pedicled pedunculated polydactyly by traditional method of suture ligation at base are also discussed. PMID- 26828691 TI - Thiamine deficiency to ward off cardiovascular dysfunction and SUDEP: Yay or nay? PMID- 26828690 TI - Neurocognitive outcome following stereotactic laser ablation in two patients with MRI-/PET+ mTLE. AB - The most effective treatment for drug-resistant seizures associated with mesial temporal lobe epilepsy (mTLE) is surgical resection. Neurocognitive sequelae may occur and are especially likely to occur after left temporal lobectomy. Smaller resections observed with selective amygdalohippocampectomy have resulted in a more favorable neurocognitive outcome in some cases when compared to standard anterior temporal lobectomy. Specifically, MRI-guided interstitial laser thermal ablation (MRgLITT) uses a superselective stereotactic amygdalohippocampotomy that has been reported to preserve object recognition and naming abilities compared with standard temporal lobe resection. We report two patients with drug-resistant mTLE and a normal high-resolution 3-T brain MRI who underwent neuropsychological assessment pre- and postleft temporal MRgLITT. Both patients demonstrated preserved visual naming ability following surgery. Semantic verbal fluency declined after surgery, but the magnitude of decline did not reach the statistical threshold for reliable change. Both patients demonstrated statistically significant and clinically meaningful declines in memory, but abilities across other nonmemory neurocognitive domains (i.e., visuospatial ability, attention) were preserved. PMID- 26828692 TI - Evaluating the safety and efficacy of felbamate in the context of a black box warning: A single center experience. AB - INTRODUCTION: Felbamate was approved in 1993 to treat partial seizures with and without secondary generalization in adults and in Lennox-Gastaut Syndrome in children. Its use was later restricted when rare but fatal cases of aplastic anemia and hepatic failure were identified. METHODS: This single center analysis retrospectively evaluated the safety and efficacy of felbamate in a cohort of children, adolescents, and adults with epilepsy. RESULTS: A chart review identified 103 patients taking felbamate. The range of felbamate dose was 300 4500 mg (mean: 1800 +/- 900 mg). The duration of therapy ranged from 1 month to 20 years (mean duration: 35 +/- 45 months). Eighteen (17.5%) subjects experienced adverse events including insomnia, nausea, vomiting, decreased appetite, weight loss, gastric discomfort, diarrhea, mood and behavioral problems, high blood pressure, headache, and elevated liver enzymes. Out of these, 6 (5.9%) patients discontinued the therapy. No hepatic failure or agranulocytosis was observed. Fifty-nine (57.72%) patients achieved >= 50% reduction in seizure frequency, and 30 (29.12%) patients achieved seizure freedom. CONCLUSIONS: These findings suggest that felbamate is safe, well tolerated, and effective in treatment of various types of epilepsy syndromes. PMID- 26828693 TI - Adjunctive retigabine in refractory focal epilepsy: Postmarketing experience at four tertiary epilepsy care centers in Germany. AB - PURPOSE: Retigabine (RTG, ezogabine) is the first potassium channel-opening anticonvulsant drug approved for adjunctive treatment of focal epilepsies. We report on the postmarketing clinical efficacy, adverse events, and retention rates of RTG in adult patients with refractory focal epilepsy. METHODS: Clinical features before and during RTG treatment were retrospectively collected from patients treated at four German epilepsy centers in 2011 and 2012. RESULTS: A total of 195 patients were included. Daily RTG doses ranged from 100 to 1500 mg. Retigabine reduced seizure frequency or severity for 24.6% and led to seizure freedom in 2.1% of the patients but had no apparent effect in 43.1% of the patients. Seizure aggravation occurred in 14.9%. The one-, two-, and three-year retention rates amounted to 32.6%, 7.2%, and 5.7%, respectively. Adverse events were reported by 76% of the patients and were mostly CNS-related. Blue discolorations were noted in three long-term responders. Three possible SUDEP cases occurred during the observation period, equalling an incidence rate of about 20 per 1000 patient years. CONCLUSIONS: Our results are similar to other pivotal trials with respect to the long-term, open-label extensions and recent postmarketing studies. Despite the limitations of the retrospective design, our observational study suggests that RTG leads to good seizure control in a small number of patients with treatment-refractory seizures. However, because of the rather high percentage of patients who experienced significant adverse events, we consider RTG as a drug of reserve. PMID- 26828694 TI - Impairment of thiol-disulfide homeostasis in preeclampsia. AB - AIM: To investigate the effects of severity of preeclampsia on thiol-disulfide homeostasis (TDH). MATERIAL AND METHODS: A total of 108 participants were divided into three groups: Group 1 was composed of pregnant women with no obstetric complications, Group 2 included pregnant women with mild preeclampsia, and Group 3 consisted of pregnant women with severe preeclampsia. TDH parameters were determined, and comparisons of clinical and routine laboratory test findings were made in all groups. RESULTS: The serum native thiol level was 347.9 +/- 27.4 in the control group, 237.2 +/- 44.2 in the mild preeclampsia group, and 227.9 +/- 53.1 in the severe preeclampsia group (p < 0.001). The serum total thiol level was 376.1 +/- 31.9 in the control group, 261.8 +/- 49.4 in the mild preeclampsia group, and 248.3 +/- 57.4 in the severe preeclampsia group (p < 0.001). The disulfide level was 14.1 +/- 5.6 in the control group, 12.3 +/- 5.1 in the mild preeclampsia group, and 10.2 +/- 4.8 in the severe preeclampsia group (p = 0.001). A significant correlation between impairment in degree of TDH and severity of preeclampsia was observed. CONCLUSION: TDH was impaired in women with preeclampsia, and this impairment increased with disease severity. Therefore, impaired TDH may have a role in the etiopathogenesis of the disease. PMID- 26828695 TI - Consideration on the Long Ecological Half-Life Component of (137)Cs in Demersal Fish Based on Field Observation Results Obtained after the Fukushima Accident. AB - Radiocesium concentrations in most marine fish collected off the coast of Fukushima and surrounding prefectures have decreased with time, and four years after the Fukushima Daiichi Nuclear Power Plant accident occurred, radiocesium concentrations have generally fallen below the detectable level (ca. < 10 Bq kg( 1)-raw). Only in some demersal fish species have detectable concentration levels still been found, and even these species have showed slow radiocesium decreases. The food web was considered as the major factor causing this phenomenon; however, slow elimination rates of radiocesium from these fish species also could be the cause. The latter effect was examined by considering that the (137)Cs concentration decreasing trend in fish could be fit with a set of three exponentially decreasing components; that is, having short, intermediate, and long biological half-lives. The long ecological half-life component was calculated using a 400-1500 d period of monitoring results for Japanese rockfish (Sebastes cheni) and compared with previous reported laboratory results for biological half-life. The obtained ecological half-lives ranged from 274-365 d, and these values agreed with the biological half-life of this fish species. This result implied that the long biological half-lives of radiocesium in some demersal fish species made their radiocesium contamination periods longer. PMID- 26828696 TI - Identifying cancer origin using circulating tumor cells. AB - Circulating tumor cells (CTCs) have become an established clinical evaluation biomarker. CTC count provides a good correlation with the prognosis of cancer patients, but has only been used with known cancer patients, and has been unable to predict the origin of the CTCs. This study demonstrates the analysis of CTCs for the identification of their primary cancer source. Twelve mL blood samples were equally dispensed on 6 CMx chips, microfluidic chips coated with an anti EpCAM-conjugated supported lipid bilayer, for CTC capture and isolation. Captured CTCs were eluted to an immunofluorescence (IF) staining panel consisting of 6 groups of antibodies: anti-panCK, anti-CK18, anti-CK7, anti-TTF-1, anti-CK20/anti CDX2, and anti-PSA/anti-PSMA. Cancer cell lines of lung (H1975), colorectal (DLD 1, HCT-116), and prostate (PC3, DU145, LNCaP) were selected to establish the sensitivity and specificity for distinguishing CTCs from lung, colorectal, and prostate cancer. Spiking experiments performed in 2mL of culture medium or whole blood proved the CMx platform can enumerate cancer cells of lung, colorectal, and prostate. The IF panel was tested on blood samples from lung cancer patients (n = 3), colorectal cancer patients (n = 5), prostate cancer patients (n = 5), and healthy individuals (n = 12). Peripheral blood samples found panCK(+) and CK18(+) CTCs in lung, colorectal, and prostate cancers. CTCs expressing CK7(+) or TTF 1(+), (CK20/ CDX2)(+), or (PSA/ PSMA)(+) corresponded to lung, colorectal, or prostate cancer, respectively. In conclusion, we have designed an immunofluorescence staining panel to identify CTCs in peripheral blood to correctly identify cancer cell origin. PMID- 26828697 TI - Evaluating the Safety of Somatic Periosteal Cells by Flow-Cytometric Analysis Monitoring the History of DNA Damage. AB - In preparing cell-based products for regenerative therapy, cell quality should be strictly controlled. Methodologies for evaluating cell viability, identity, and purity are established and used routinely, whereas current methodologies for evaluating cell safety, particularly genetic integrity or tumorigenicity, are time-consuming and relatively insensitive. As part of developing a more practical screening system, the authors previously demonstrated that gamma-H2AX and p53 were useful markers for evaluating the history of DNA damage. To validate these markers further and develop a more quantitative methodology, single cell-based expression of these markers and two additional candidates have now been examined using flow cytometry (FCM). FCM analysis and immunofluorescent staining demonstrated that gamma-ray-irradiation suppressed proliferation, enlarged cells, and cell nuclei, and immediately upregulated gamma-H2AX and p21(waf1) in large numbers of cells for up to 12 days. Gamma-H2AX foci were formed in the nuclei of many affected cells. An initial sharp increase in p53 expression declined slowly over 12 days, while Rb expression increased linearly. The present findings suggest that this high-throughput, cell-based, combinational evaluation of protein markers and cell size enables a small number of cells with a history of DNA damage to be detected quickly and routinely from within a very large cell population. Using this screening methodology will improve the ability to verify the quality of cell-based products used in regenerative therapy. PMID- 26828698 TI - Effect of MTHFR Gene Polymorphism Impact on Atherosclerosis via Genome-Wide Methylation. AB - BACKGROUND: Atherosclerosis seriously threats human health. Homocysteine is an independent risk factor closely related to DNA methylation. MTHFR C667T loci polymorphism is closely associated with homocysteine level. This study aimed to investigate the relationship among MTHFR C667T loci polymorphism, genome-wide methylation, and atherosclerosis. MATERIAL/METHODS: Blood sample was collected from 105 patients with coronary atherosclerosis and 105 healthy controls. Pyrosequencing methylation was used to detect LINE-1 methylation level. Polymerase chain reaction-restriction enzyme fragment length polymorphism (PCR RFLP) was used to test MTHFR. RESULTS: LINE-1 methylation level in the patient group was significantly lower than in the controls (t=5.007, P<0.001). MTHFR C667T genotype distribution presented marked differences in the 2 groups. TT genotype carriers had significantly increased risk of atherosclerosis (OR=3.56, P=0.009). Three different genotypes of MTHFR C667T loci showed different LINE-1 methylation level between the 2 groups (P<0.01). LINE-1 methylation level in TT and CT genotype carriers was obviously lower than in CC genotype carriers (P<0.05). CONCLUSIONS: MTHFR C667T loci polymorphism may affect atherosclerosis by regulating genome methylation level. PMID- 26828699 TI - Effect of pH on structure, function, and stability of mitochondrial carbonic anhydrase VA. AB - Mitochondrial carbonic anhydrase VA (CAVA) catalyzes the hydration of carbon dioxide to produce proton and bicarbonate which is primarily expressed in the mitochondrial matrix of liver, and involved in numerous physiological processes including lipogenesis, insulin secretion from pancreatic cells, ureagenesis, gluconeogenesis, and neuronal transmission. To understand the effect of pH on the structure, function, and stability of CAVA, we employed spectroscopic techniques such as circular dichroism, fluorescence, and absorbance measurements in wide range of pH (from pH 2.0 to pH 11.5). CAVA showed an aggregation at acidic pH range from pH 2.0 to pH 5.0. However, it remains stable and maintains its secondary structure in the pH range, pH 7.0-pH 11.5. Furthermore, this enzyme has an appreciable activity at more than pH 7.0 (7.0 < pH <= 11.5) with maximum activity at pH 9.0. The maximal values of kcat and kcat/Km at pH 9.0 are 3.7 * 106 s-1 and 5.5 * 107 M-1 s-1, respectively. However, this enzyme loses its activity in the acidic pH range. We further performed 20-ns molecular dynamics simulation of CAVA to see the dynamics at different pH values. An excellent agreement was observed between in silico and in vitro studies. This study provides an insight into the activity of CAVA in the pH range of subcellular environment. PMID- 26828700 TI - Targeting miR-155 to Treat Experimental Scleroderma. AB - Scleroderma is a refractory autoimmune skin fibrotic disorder. Alterations of microRNAs in lesional skin could be a new approach to treating the disease. Here, we found that expression of miR-155 was up regulated in lesional skin tissue from patients with either systemic or localized scleroderma, and correlated with fibrosis area. Then we demonstrated the potential of miR-155 as a therapeutic target in pre-clinical scleroderma models. MiR-155(-/-) mice were resistant to bleomycin induced skin fibrosis. Moreover, topical antagomiR-155 could effectively treat mice primed with subcutaneous bleomycin. In primary skin fibroblast, miR-155 silencing could inhibit collagen synthesis function, as well as signaling intensity of two pro-fibrotic pathways, Wnt/beta-catenin and Akt, simultaneously. We further showed that miR-155 could regulate the two pathways via directly targeting casein kinase 1alpha (CK1alpha) and Src homology 2 containing inositol phosphatase-1 (SHIP-1), as previous reports. Mice with miR 155 knockout or topical antagomir-155 treatment showed inhibited Wnt/beta-catenin and Akt signaling in skin upon bleomycin challenge. Together, our data suggest the potential of miR-155 silencing as a promising treatment for dermal fibrosis, especially in topical applications. PMID- 26828701 TI - Discharge criteria for Crimean-Congo haemorrhagic fever in endemic areas. PMID- 26828703 TI - Understanding the Mechanism of the Lewis Acid Promoted [3 + 2] Cycloaddition of Propargylic Alcohol and alpha-Oxo Ketene Dithioacetals. AB - The mechanism and origin of selectivities in BF3.Et2O-catalyzed intermolecular [3 + 2] cycloadditions of propargylic alcohol and alpha-oxo ketene dithioacetals have been studied using density functional theory. Several possible reaction pathways were evaluated on the basis of two possible binding modes between the carbonyl or hydroxyl oxygen of substrates and catalyst. The preferred mechanism initiates dehydroxylation of propargylic alcohol by Lewis acid BF3 and generates active allenic carbocation species to provide the favorable electrophile. It then proceeds via four processes involving nucleophilic addition of C(alpha) on alpha oxo ketene dithioacetals to the C1 of active allenic carbocation intermediate, [1,4]-alkylthio shift, H(alpha)-elimination, and intramolecular cyclization. This reaction sequence is in contrast to the mechanism by a previously published study, that is, [1,4]-alkylthio migration occurs prior to the cyclization. Our calculated results suggested that electrostatic attraction and hydrogen-bonding interactions between substrates and catalyst play a vital role in the [3 + 2] cycloaddition. PMID- 26828704 TI - Improvement in Titanium Complexes Bearing Schiff Base Ligands in the Ring-Opening Polymerization of L-Lactide: A Dinuclear System with Hydrazine-Bridging Schiff Base Ligands. AB - A series of titanium (Ti) complexes bearing hydrazine-bridging Schiff base ligands were synthesized and investigated as catalysts for the ring-opening polymerization (ROP) of L-lactide (LA). Complexes with electron withdrawing or steric bulky groups reduced the catalytic activity. In addition, the steric bulky substituent on the imine groups reduced the space around the Ti atom and then reduced LA coordination with Ti atom, thereby reducing catalytic activity. All the dinuclear Ti complexes exhibited higher catalytic activity (approximately 10 60-fold) than mononuclear L(Cl-H)-TiOPr2 did. The strategy of bridging dinuclear Ti complexes with isopropoxide groups in the ROP of LA was successful, and adjusting the crowded heptacoordinated transition state by the bridging isopropoxide groups may be the key to our successful strategy. PMID- 26828705 TI - Correction to "Glycosylation of Human Plasma Clusterin Yields a Novel Candidate Biomarker of Alzheimer's Disease". PMID- 26828706 TI - Efficient modelling of droplet dynamics on complex surfaces. AB - This work investigates the dynamics of droplet interaction with smooth or structured solid surfaces using a novel sharp-interface scheme which allows the efficient modelling of multiple dynamic contact lines. The liquid-gas and liquid solid interfaces are treated in a unified context and the dynamic contact angle emerges simply due to the combined action of the disjoining and capillary pressure, and viscous stresses without the need of an explicit boundary condition or any requirement for the predefinition of the number and position of the contact lines. The latter, as it is shown, renders the model able to handle interfacial flows with topological changes, e.g. in the case of an impinging droplet on a structured surface. Then it is possible to predict, depending on the impact velocity, whether the droplet will fully or partially impregnate the structures of the solid, or will result in a 'fakir', i.e. suspended, state. In the case of a droplet sliding on an inclined substrate, we also demonstrate the built-in capability of our model to provide a prediction for either static or dynamic contact angle hysteresis. We focus our study on hydrophobic surfaces and examine the effect of the geometrical characteristics of the solid surface. It is shown that the presence of air inclusions trapped in the micro-structure of a hydrophobic substrate (Cassie-Baxter state) result in the decrease of contact angle hysteresis and in the increase of the droplet migration velocity in agreement with experimental observations for super-hydrophobic surfaces. Moreover, we perform 3D simulations which are in line with the 2D ones regarding the droplet mobility and also indicate that the contact angle hysteresis may be significantly affected by the directionality of the structures with respect to the droplet motion. PMID- 26828707 TI - Adoption of Certified Electronic Health Record Systems and Electronic Information Sharing in Physician Offices: United States, 2013 and 2014. AB - KEY FINDINGS: Data from the 2014 National Electronic Health Records Survey. In 2014, 74.1% of office-based physicians had a certified electronic health record (EHR) system, up from 67.5% in 2013. The percentage of physicians who had a certified EHR system ranged from 58.8% in Alaska to 88.6% in Minnesota. In 2014, 32.5% of office-based physicians with a certified EHR system were electronically sharing patient health information with external providers. The percentage of physicians with a certified EHR system electronically sharing patient health information with external providers ranged from 17.7% in New Jersey to 58.8% in North Dakota. PMID- 26828702 TI - Cognitive Function as a Transdiagnostic Treatment Target in Stimulant Use Disorders. AB - Stimulant use disorder is an important public health problem, with an estimated 2.1 million current users in the United States alone. No pharmacological treatments are approved by the U.S. Food and Drug Administration for stimulant use disorder and behavioral treatments have variable efficacy and limited availability. Most individuals with stimulant use disorder have other comorbidities, most with overlapping symptoms and cognitive impairments. The goal of this article is to present a rationale for cognition as a treatment target in stimulant use disorder and to outline potential treatment approaches. Rates of lifetime comorbid psychiatric disorders among people with stimulant use disorders are estimated at 65% to 73%, with the most common being mood disorders (13% to 64%) and anxiety disorders (21% to 50%), as well as non-substance-induced psychotic disorders (<10%). There are several models of addictive behavior, but the dual process model particularly highlights the relevance of cognitive impairments and biases to the development and maintenance of addiction. This model explains addictive behavior as a balance between automatic processes and executive control, which in turn are related to individual (genetics, comorbid disorders, psychosocial factors) and other (craving, triggers, drug use) factors. Certain cognitive impairments, such as attentional bias and approach bias, are most relevant to automatic processes, while sustained attention, response inhibition, and working memory are primarily related to executive control. These cognitive impairments and biases are also common in disorders frequently comorbid with stimulant use disorder and predict poor treatment retention and clinical outcomes. As such, they may serve as feasible transdiagnostic treatment targets. There are promising pharmacological, cognitive, and behavioral approaches that aim to enhance cognitive function. Pharmacotherapies target cognitive impairments associated with executive control and include cholinesterase inhibitors (e.g., galantamine, rivastigmine) and monoamine transporter inhibitors (e.g., modafinil, methylphenidate). Cognitive behavioral therapy and cognitive rehabilitation also enhance executive control, while cognitive bias modification targets impairments associated with automatic processes. Cognitive enhancement to improve treatment outcomes is a novel and promising strategy, but its clinical value for the treatment of stimulant use disorder, with or without other psychiatric comorbidities, remains to be determined in future studies. PMID- 26828708 TI - Assessing risk for aggression in forensic psychiatric inpatients: An examination of five measures. AB - The present study examined risk for inpatient aggression, including treatment related changes in risk, using a battery of 5 forensic instruments. The relative contributions of different types of risk factors to the assessment of risk for inpatient outcomes were also assessed. The Historical-Clinical-Risk Management 20V3, Short-Term Assessment of Risk and Treatability, Violence Risk Scale, Violence Risk Appraisal Guide-Revised, and Psychopathy Checklist-Revised were rated from archival information sources on a sample of 99 adult forensic inpatients from a Canadian psychiatric hospital. Pretreatment and posttreatment ratings were obtained on all dynamic study measures; associations between risk and change ratings with inpatient aggression were examined. Significant pretreatment-posttreatment differences were found on the HCR-20V3, START, and VRS; pretreatment scores on these measures each demonstrated predictive accuracy for inpatient aggression (AUC = .68 to .76) whereas the PCL-R and VRAG-R did not. HCR-20V3, VRS, and START dynamic scores demonstrated incremental predictive validity for inpatient aggression to varying degrees after controlling for static risk factors. Dynamic change scores from these 3 measures also demonstrated incremental concurrent associations with reductions in inpatient aggression after controlling for baseline risk. Several instruments demonstrated predictive validity for inpatient aggression and clinical/dynamic risk and change scores had unique associations with this outcome. The present findings suggest that risk assessments using the HCR-20 V3, START, and VRS may inform the management and reduction of inpatient aggression, as well as assessments of dynamic risk more generally. (PsycINFO Database Record PMID- 26828709 TI - A critical examination of "being Black" in the juvenile justice system. AB - The current study examined the role of race in juvenile court outcomes across 3 decision-making stages. This analysis was conducted with a random sample of all delinquent referrals in a Northeast state from January 2000 through December 2010 (N = 68,188). In addition to traditional logistic regression analysis, a propensity score matching (PSM) approach was utilized to create comparable samples of Black and White youth and provide a more rigorous methodological test of the relationship between race and juvenile court processing. Results indicated that even after the use of PSM techniques, race was still found to influence the likelihood of intake (OR = 1.54; 95% C.I. = 1.48-1.62, p < .001), adjudication (OR = 0.80; 95% C.I. = 0.76-0.84, p < .001), and disposition (OR = 1.64; 95% C.I. = 1.54-1.76, p < .001) outcomes. The findings show that Black youth received disadvantaged court outcomes at 2 of the 3 stages, even after balancing both groups on a number of confounders. Black youth were treated harsher at intake and judicial disposition, but received leniency at adjudication compared with similarly situated Whites. These relationships were the most evident at the stage of judicial disposition. The findings impact both researchers' and policymakers' strategies to more fully understand the complex relationship between race and social control. They also reaffirm the noticeable role that selection bias can play in the research surrounding race differences in juvenile court outcomes, and highlight the importance of utilizing a more stringent statistical model to control for selection bias. (PsycINFO Database Record PMID- 26828710 TI - Duration of Posttraumatic Amnesia Predicts Neuropsychological and Global Outcome in Complicated Mild Traumatic Brain Injury. AB - OBJECTIVES: Examine the effects of posttraumatic amnesia (PTA) duration on neuropsychological and global recovery from 1 to 6 months after complicated mild traumatic brain injury (cmTBI). PARTICIPANTS: A total of 330 persons with cmTBI defined as Glasgow Coma Scale score of 13 to 15 in emergency department, with well-defined abnormalities on neuroimaging. METHODS: Enrollment within 24 hours of injury with follow-up at 1, 3, and 6 months. MEASURES: Glasgow Outcome Scale Extended, California Verbal Learning Test II, and Controlled Oral Word Association Test. Duration of PTA was retrospectively measured with structured interview at 30 days postinjury. RESULTS: Despite all having a Glasgow Coma Scale Score of 13 to 15, a quarter of the sample had a PTA duration of greater than 7 days; half had PTA duration of 1 of 7 days. Both cognitive performance and Extended Glasgow Outcome Scale outcomes were strongly associated with time since injury and PTA duration, with those with PTA duration of greater than 1 week showing residual moderate disability at 6-month assessment. CONCLUSIONS: Findings reinforce importance of careful measurement of duration of PTA to refine outcome prediction and allocation of resources to those with cmTBI. Future research would benefit from standardization in computed tomographic criteria and use of severity indices beyond Glasgow Coma Scale to characterize cmTBI. PMID- 26828711 TI - Effects of Depression and Antidepressant Use on Cognitive Deficits and Functional Cognition Following Severe Traumatic Brain Injury. AB - OBJECTIVE: To use a Rehabilomics framework to evaluate relations hips between post-traumatic brain injury (TBI) depression (PTD) and potential associated factors, including antidepressant use, on cognitive recovery following severe TBI. PARTICIPANTS: Severe TBI survivors (n = 154), recruited from a level 1 trauma center. DESIGN: Prospective cohort study with assessments at 6 and 12 months postinjury. MAIN MEASURES: Patient Health Questionnaire-9 (PTD symptoms); cognitive composite score from a neuropsychological assessment battery (cognitive impairment); and Functional Independence Measure-Cognition (FIM-Cog, self reported functional cognition). RESULTS: Individuals with and without PTD did not differ with respect to cognitive impairment. However, antidepressant use, regardless of PTD status, was associated with cognitive impairment. Individuals with PTD reported lower FIM-Cog scores at both time points compared with those without PTD. In a post hoc longitudinal analysis, individuals with late-onset PTD had worse cognitive impairment. CONCLUSION: These results suggest that antidepressant use impairs cognition among individuals without PTD. Also, PTD did not directly affect cognitive impairment but may affect functional cognitive limitations through self-evaluation and apathy/motivation factors. PMID- 26828712 TI - Algorithm for Symptom Attribution and Classification Following Possible Mild Traumatic Brain Injury. AB - OBJECTIVE: To present a heuristic model of a symptom attribution and classification algorithm (SACA) for mild traumatic brain injury (mTBI). SETTING: VA Polytrauma sites. PARTICIPANTS: 422 Veterans. DESIGN: Cross-sectional. MAIN MEASURES: SACA, Comprehensive TBI Evaluation (CTBIE), Structured TBI Diagnostic Interview, Minnesota Multiphasic Personality Inventory (MMPI-2-RF), Letter Memory Test, Validity-10. RESULTS: SACA and CTBIE diagnoses differ significantly (P < .01). The CTBIE, compared with SACA, attributes 16% to 500% more symptoms to mTBI, behavioral health (BH), mTBI + BH and symptom resolution. Altering SACA criteria indicate that (1) CTBIE determination of cognitive impairment yields 27% to 110% more mTBI, mTBI + BH and symptom resolution diagnoses, (2) ignoring timing of symptom onset yields 32% to 76% more mTBI, mTBI + BH and Other Condition diagnoses, (3) Proportion of sample having questionably valid profiles using structured TBI diagnostic interview and MMPI-2-RF and Letter Memory Test is 26% whereas with CTBIE item number 23 and Validity-10 is 6% to 26%, (4) MMPI-2-RF F-scale is the only measure identifying Veterans with posttraumatic amnesia for more than 24 hours as having questionably valid profiles. CONCLUSIONS: Symptom attribution-based diagnoses differ when using status quo versus the SACA. The MMPI-2-RF F-scale, compared with the Validity-10 and Letter Memory Test, may be more precise in identifying questionably valid profiles for mTBI + BH. The SACA provides a framework to inform clinical practice, resource allocation, and future research. PMID- 26828713 TI - Long-Term School Outcomes of Children and Adolescents With Traumatic Brain Injury. AB - OBJECTIVE: To better understand the impact of age at injury, severity of injury, and time since injury on long-term school outcomes of children with traumatic brain injury (TBI). PARTICIPANTS: Four groups of children: complicated mild/moderate TBI (n = 23), severe TBI (n = 56), orthopedic injury (n = 35), and healthy controls (n = 42). Children with TBI were either 2 years postinjury or 6 years postinjury. DESIGN: Cross-sectional design. MEASURES: School records as well as parental ratings of functional academic skills and school competency. RESULTS: Children with severe TBI had consistently high usage of school services and low school competency ratings than children with orthopedic injuries and healthy controls. In contrast, children with complicated-mild/moderate TBI were significantly more likely to receive school support services and have lower competence ratings at 6 years than at 2 years postinjury. Students injured at younger ages had lower functional academic skill ratings than those injured at older ages. CONCLUSIONS: These findings highlight the increasing academic challenges faced over time by students with complicated-mild/moderate TBI and the vulnerability of younger children to poorer development of functional academic skills. PMID- 26828715 TI - Self-Awareness and Self-Ratings of On-Road Driving Performance After Traumatic Brain Injury. AB - OBJECTIVE: To examine self-rated, clinician-rated, and self-awareness of on-road driving performance in individuals with traumatic brain injury (TBI) deemed fit and unfit to resume driving and healthy controls, and to explore their associations with demographic, injury, cognitive, and mood variables. METHODS: Participants included 37 individuals with moderate to severe TBI, and 49 healthy age, sex, and education-matched controls from Australia and Canada. Participants completed an on-road assessment, the Brain Injury Driving Self-Awareness Measure (BIDSAM), and a comprehensive neuropsychological assessment. RESULTS: Awareness scores on the BIDSAM were significantly different between groups, F(2, 83) = 28.44 (P < .001; eta = 0.41), with post hoc tests indicating TBI participants who failed the on-road assessment had worse scores compared with those who passed and controls. Poor self-awareness was significantly correlated with reduced psychomotor speed (rs = -0.37; P < .01) and attentional switching (rs = 0.28; P < .01). Worse self-ratings of driving were associated with depression (rs = 0.42; P < .01) and anxiety (rs = 0.38; P < .01). CONCLUSIONS: Individuals with TBI who failed an on-road assessment significantly overestimated their driving ability. Impaired cognitive function was associated with reduced self-awareness of driving. These findings suggest impaired awareness of driving may need to be addressed as part of driver rehabilitation programs. PMID- 26828716 TI - Management of localized and advanced prostate cancer in Canada: A lifetime cost and quality-adjusted life-year analysis. AB - BACKGROUND: To the authors' knowledge, the literature to date lacks studies examining lifetime costs and quality-adjusted life-years (QALYs) of prostate cancer (PCa) management strategies that integrate localized and advanced disease. The objective of the current study was to assess lifetime costs and QALYs associated with contemporary PCa management strategies across risk groups by integrating localized and advanced disease. METHODS: The authors' validated Markov chain Monte Carlo model was used to predict lifetime direct costs and QALYs. The health states modeled were active surveillance, initial treatments (radical prostatectomy or radiotherapy), PCa recurrence, PCa recurrence free, metastatic castration-resistant prostate cancer, and death (cause specific/other causes). Data regarding treatment distribution, state transition probabilities, adverse effects of management options, costs, utilities, and disutilities were derived from the published literature. RESULTS: The total cost per patient for the overall cohort increased from $18,503 at 5 years to $28,032 and $39,143, respectively, at 10 years and 15 years. Furthermore, the results indicated the influence of risk group on total cost, with the high-risk group accruing the maximum per patient cost followed by the intermediate-risk and low-risk groups. Active surveillance was found to confer the most QALYs (12.5 years) and was the least costly strategy ($18,452) for individuals at low risk. For all risk groups, radical prostatectomy was less costly and conferred modestly more QALYs compared with intensity-modulated radiotherapy modalities. CONCLUSIONS: Public health care systems in Canada and elsewhere are operating under budget constraints to allocate finite resources. The findings of the current study might inform discussions concerning budget planning to provide health care services. PMID- 26828714 TI - Genetic Variation in the Vesicular Monoamine Transporter: Preliminary Associations With Cognitive Outcomes After Severe Traumatic Brain Injury. AB - INTRODUCTION: Traumatic brain injury (TBI) frequently results in impaired cognition, a function that can be modulated by monoaminergic signaling. Genetic variation among monoaminergic genes may affect post-TBI cognitive performance. The vesicular monoamine transporter-2 (VMAT2) gene may be a novel source of genetic variation important for cognitive outcomes post-TBI given VMAT2's role in monoaminergic neurotransmission. OBJECTIVE: To evaluate associations between VMAT2 variability and cognitive outcomes post-TBI. METHODS: We evaluated 136 white adults with severe TBI for variation in VMAT2 using a tagging single nucleotide polymorphism (tSNP) approach (rs363223, rs363226, rs363251, and rs363341). We show genetic variation interacts with assessed cognitive impairment (cognitive composite [Comp-Cog] T-scores) to influence functional cognition (functional independence measure cognitive [FIM-Cog] subscale] 6 and 12 months postinjury. RESULTS: Multivariate analyses at 6 months postinjury showed rs363226 genotype was associated with Comp-Cog (P = .040) and interacted with Comp-Cog to influence functional cognition (P < .001). G-homozygotes had the largest cognitive impairment, and their cognitive impairment had the greatest adverse effect on functional cognition. DISCUSSION: We provide the first evidence that genetic variation within VMAT2 is associated with cognitive outcomes after TBI. Further work is needed to validate this finding and elucidate mechanisms by which genetic variation affects monoaminergic signaling, mediating differences in cognitive outcomes. PMID- 26828717 TI - l-Theanine inhibits proinflammatory PKC/ERK/ICAM-1/IL-33 signaling, apoptosis, and autophagy formation in substance P-induced hyperactive bladder in rats. AB - AIMS: Upregulation of substance P (SP) and neurokinin-1 receptor (NK1R) activation induces pro-inflammatory bladder hyperactivity through the PKC/ERK/NF kappaB/ICAM-1/IL-33 signaling pathways to increase the leukocyte infiltration and adhesion leading to reactive oxygen species (ROS) production, autophagy, and apoptosis. l-Theanine is a unique non-protein-forming amino acid present in tea (Camellia sinensis [L.] O. Kuntze) with its antioxidant, anti-inflammatory, and relaxation effects to improve cognition, mood, gastric ulcer injury, and cerebral ischemia/reperfusion injury, and posttraumatic stress disorder. We explored the protective effect of l-theanine on SP-induced bladder hyperactivity. METHODS: In urethane-anesthetized female Wistar rats, we explored the transcystometrogram, pelvic nerve activity, proinflammatory PKC/ERK/NF-kappaB/ICAM-1/IL-33 signaling, apoptosis-related Caspase 3/poly-(ADP-ribose)-polymerase (PARP), and autophagy mediated LC3 II expression by Western blot, electrophoretic-mobility shift assay and immunohistochemistry, bladder ROS amount by a ultrasensitive chemiluminescence method, and possible ROS sources from the different leukocytes by specific stains in SP-evoked hyperactive bladder. RESULTS: l-Theanine dose dependently depressed H2 O2 and HOCl activity in vitro. In urethane-anesthetized female Wistar rats, intra-arterial SP through NK1R activation increased voiding frequency (shortened intercontraction intervals) associated with the increase in bladder nerve activity, proinflammatory PKC/ERK/NF-kappaB/ICAM-1/IL-33 signaling, Caspase 3/PARP-mediated apoptosis, LC3 II-mediated autophagy, ROS amount, neutrophils adhesion, CD68 (monocyte/macrophage) infiltration, and mast cells degranulation in the hyperactive bladder. Intragastrical l-theanine (15 mg/kg) twice daily for 2 weeks efficiently ameliorated all the enhanced parameters in the SP-treated hyperactive bladder. CONCLUSIONS: In conclusion, l-theanine through antioxidant and anti-inflammatory actions ameliorates SP-induced bladder hyperactivity via the inhibition of proinflammatory PKC/ERK/NF-kappaB/ICAM-1/IL 33 signaling, oxidative stress, bladder nerve hyperactivity, apoptosis, and autophagy. Neurourol. Urodynam. 36:297-307, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26828718 TI - Neuropathogenicity of Two Saffold Virus Type 3 Isolates in Mouse Models. AB - OBJECTIVE: Saffold virus (SAFV), a picornavirus, is occasionally detected in children with acute flaccid paralysis, meningitis, and cerebellitis; however, the neuropathogenicity of SAFV remains undetermined. METHODS: The virulence of two clinical isolates of SAFV type 3 (SAFV-3) obtained from a patient with aseptic meningitis (AM strain) and acute upper respiratory inflammation (UR strain) was analyzed in neonatal and young mice utilizing virological, pathological, and immunological methods. RESULTS: The polyproteins of the strains differed in eight amino acids. Both clinical isolates were infective, exhibited neurotropism, and were mildly neurovirulent in neonatal ddY mice. Both strains pathologically infected neural progenitor cells and glial cells, but not large neurons, with the UR strain also infecting epithelial cells. UR infection resulted in longer inflammation in the brain and spinal cord because of demyelination, while the AM strain showed more infectivity in the cerebellum in neonatal ddY mice. Additionally, young BALB/c mice seroconverted following mucosal inoculation with the UR, but not the AM, strain. CONCLUSIONS: Both SAFV-3 isolates had neurotropism and mild neurovirulence but showed different cell tropisms in both neonatal and young mouse models. This animal model has the potential to recapitulate the potential neuropathogenicity of SAFV-3. PMID- 26828719 TI - GBStools: A Statistical Method for Estimating Allelic Dropout in Reduced Representation Sequencing Data. AB - Reduced representation sequencing methods such as genotyping-by-sequencing (GBS) enable low-cost measurement of genetic variation without the need for a reference genome assembly. These methods are widely used in genetic mapping and population genetics studies, especially with non-model organisms. Variant calling error rates, however, are higher in GBS than in standard sequencing, in particular due to restriction site polymorphisms, and few computational tools exist that specifically model and correct these errors. We developed a statistical method to remove errors caused by restriction site polymorphisms, implemented in the software package GBStools. We evaluated it in several simulated data sets, varying in number of samples, mean coverage and population mutation rate, and in two empirical human data sets (N = 8 and N = 63 samples). In our simulations, GBStools improved genotype accuracy more than commonly used filters such as Hardy Weinberg equilibrium p-values. GBStools is most effective at removing genotype errors in data sets over 100 samples when coverage is 40X or higher, and the improvement is most pronounced in species with high genomic diversity. We also demonstrate the utility of GBS and GBStools for human population genetic inference in Argentine populations and reveal widely varying individual ancestry proportions and an excess of singletons, consistent with recent population growth. PMID- 26828720 TI - Ionizing Radiation Induces Altered Neuronal Differentiation by mGluR1 through PI3K-STAT3 Signaling in C17.2 Mouse Neural Stem-Like Cells. AB - Most studies of IR effects on neural cells and tissues in the brain are still focused on loss of neural stem cells. On the other hand, the effects of IR on neuronal differentiation and its implication in IR-induced brain damage are not well defined. To investigate the effects of IR on C17.2 mouse neural stem-like cells and mouse primary neural stem cells, neurite outgrowth and expression of neuronal markers and neuronal function-related genes were examined. To understand this process, the signaling pathways including PI3K, STAT3, metabotrophic glutamate receptor 1 (mGluR1) and p53 were investigated. In C17.2 cells, irradiation significantly increased the neurite outgrowth, a morphological hallmark of neuronal differentiation, in a dose-dependent manner. Also, the expression levels of neuronal marker proteins, beta-III tubulin were increased by IR. To investigate whether IR-induced differentiation is normal, the expression of neuronal function-related genes including synaptophysin, a synaptic vesicle forming proteins, synaptotagmin1, a calcium ion sensor, gamma-aminobutyric acid (GABA) receptors, inhibitory neurotransmitter receptors and glutamate receptors, excitatory neurotransmitter receptors was examined and compared to that of neurotrophin-stimulated differentiation. IR increased the expression of synaptophysin, synaptotagmin1 and GABA receptors mRNA similarly to normal differentiation by stimulation of neurotrophin. Interestingly, the overall expression of glutamate receptors was significantly higher in irradiated group than normal differentiation group, suggesting that the IR-induced neuronal differentiation may cause altered neuronal function in C17.2 cells. Next, the molecular mechanism of the altered neuronal differentiation induced by IR was studied by investigating signaling pathways including p53, mGluR1, STAT3 and PI3K. Increases of neurite outgrowth, neuronal marker and neuronal function related gene expressions by IR were abolished by inhibition of p53, mGluR-1, STAT3 or PI3K. The inhibition of PI3K blocked both p53 signaling and STAT3-mGluR1 signaling but inhibition of p53 did not affect STAT3-mGluR1 signaling in irradiated C17.2 cells. Finally, these results of the IR-induced altered differentiation in C17.2 cells were verified in ex vivo experiments using mouse primary neural stem cells. In conclusion, the results of this study demonstrated that IR is able to trigger the altered neuronal differentiation in undifferentiated neural stem-like cells through PI3K-STAT3-mGluR1 and PI3K-p53 signaling. It is suggested that the IR-induced altered neuronal differentiation may play a role in the brain dysfunction caused by IR. PMID- 26828722 TI - Effects of CreERT2, 4-OH Tamoxifen, and Gender on CFU-F Assays. AB - Gene function in stem cell maintenance is often tested by inducing deletion via the Cre-loxP system. However, controls for Cre and other variables are frequently not included. Here we show that when cultured in the presence of 4-OH tamoxifen, bone and marrow cells containing the CreERT2 construct have a reduced colony forming ability. Inactive CreERT2 recombinase, however, has the opposite effect. Young female marrow cells containing the inactive CreERT2 construct grew more colonies than cells lacking the construct altogether. Young female control marrow cells (i.e., negative for CreERT2) also produced significantly greater colony numbers when cultured with 4-OH tamoxifen, compared with the ethanol vehicle control. In conclusion, we report that the use of the Cre-loxP system is inadvisable in combination with CFU-F assays, and that appropriate controls should be in place to extend the future use of Cre-loxP in alternate assays. PMID- 26828724 TI - Degradation of aldrin and endosulfan in rotary drum and windrow composting. AB - Removal efficiencies, kinetics and degradation pathways of aldrin, endosulfan alpha and endosulfan beta in vegetable waste were evaluated during rotary drum and conventional windrow composting. The highest percentage removal of aldrin, endosulfan alpha and endosulfan beta in rotary drum composting was 86.8, 83.3 and 85.3% respectively, whereas in windrow composting, it was 66.6%, 77.7% and 67.2% respectively. The rate constant of degradation of aldrin, endosulfan alpha and endosulfan beta during rotary drum composting ranged from 0.410-0.778, 0.057 0.076 and 0.009-0.061 day(-1) respectively. The pathways of degradation of these pesticides in composting process were proposed. Metabolites dieldrin and 1 hydroxychlorodene formed during composting of aldrin in the vegetable waste indicated the occurrence of epoxidation reaction and oxidation of bridge carbon of aldrin containing the methylene group. Formation of chloroendic acid and chloroendic anhydride during composting of endosulfan containing vegetable waste support the occurrence of endosulfan sulfate and dehydration reaction respectively. PMID- 26828723 TI - Automated Protein Localization of Blood Brain Barrier Vasculature in Brightfield IHC Images. AB - In this paper, we present an objective method for localization of proteins in blood brain barrier (BBB) vasculature using standard immunohistochemistry (IHC) techniques and bright-field microscopy. Images from the hippocampal region at the BBB are acquired using bright-field microscopy and subjected to our segmentation pipeline which is designed to automatically identify and segment microvessels containing the protein glucose transporter 1 (GLUT1). Gabor filtering and k-means clustering are employed to isolate potential vascular structures within cryosectioned slabs of the hippocampus, which are subsequently subjected to feature extraction followed by classification via decision forest. The false positive rate (FPR) of microvessel classification is characterized using synthetic and non-synthetic IHC image data for image entropies ranging between 3 and 8 bits. The average FPR for synthetic and non-synthetic IHC image data was found to be 5.48% and 5.04%, respectively. PMID- 26828721 TI - Lipid peroxidation and apoptotic response in rat brain areas induced by long-term administration of nandrolone: the mutual crosstalk between ROS and NF-kB. AB - The aim of this study was to evaluate the played by oxidative stress in the apoptotic response in different brain areas of rats chronically treated with supra-physiological doses of nandrolone decanoate (ND). Immunohistochemical study and Western blot analysis were performed to evaluate cells' apoptosis and to measure the effects of expression of specific mediators, such as NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells), Bcl-2 (B-cell lymphoma 2), SMAC/DIABLO (second mitochondria-derived activator of caspases/direct IAP-binding protein with low PI) and VMAT2 (vesicular monoamine transporter 2) on apoptosis. The results of the present study indicate that a long-term administration of ND promotes oxidative injury in rat brain specific areas. A link between oxidative stress and NF-kappaB signalling pathways is supported by our results. In addition to high levels of oxidative stress, we consistently observed a strong immunopositivity to NF-kappaB. It has been argued that one of the pathways leading to the activation of NF-kappaB could be under reactive oxygen species (ROS)-mediated control. In fact, growing evidence suggests that although in limited doses, endogenous ROS may play an activating role in NF-kappaB signalling, while above a certain threshold, they may negatively impact upon this signalling. However, a mutual crosstalk between ROS and NF-kappaB exists and recent studies have shown that ROS activity is subject to negative feedback regulation by NF-kappaB, and that this negative regulation of ROS is the means through which NF-kappaB counters programmed cells. PMID- 26828725 TI - Pannexin-1 Deficient Mice Have an Increased Susceptibility for Atrial Fibrillation and Show a QT-Prolongation Phenotype. AB - BACKGROUND/AIMS: Pannexin-1 (Panx1) is an ATP release channel that is ubiquitously expressed and coupled to several ligand-gated receptors. In isolated cardiac myocytes, Panx1 forms large conductance channels that can be activated by Ca2+ release from the sarcoplasmic reticulum. Here we characterized the electrophysiological function of these channels in the heart in vivo, taking recourse to mice with Panx1 ablation. METHODS: Cardiac phenotyping of Panx1 knock out mice (Panx1(-/-)) was performed by employing a molecular, cellular and functional approach, including echocardiography, surface and telemetric ECG recordings with QT analysis, physical stress testing and quantification of heart rate variability. In addition, an in vivo electrophysiological study entailed programmed electrical stimulation using an intracardiac octapolar catheter. RESULTS: Panx1 deficiency results in a higher incidence of AV-block, delayed ventricular depolarisation, significant prolongation of QT- and rate corrected QT interval and a higher incidence of atrial fibrillation after intraatrial burst stimulation. CONCLUSION: Panx1 seems to play an important role in murine cardiac electrophysiology and warrants further consideration in the context of hereditary forms of atrial fibrillation. PMID- 26828727 TI - THE ABILITY TO DELAY GRATIFICATION: A TRAIT-OR NOT A TRAIT? AB - The purpose of this research was (a) to investigate with normal adults the convergence among several delay measures with different rationales and response modes; and (b) to examine the relationships between these variables and other personality measures which are theoretically tied to delay ability but whose relationships have not been empirically established. Study I included 61 undergraduates who were administered a battery of 14 measures. Study 11 included 109 males and females who were administered 22 measures. Data analysis showed (a) little convergence among the delay measures, and (b) little evidence of a. network of personality correlates of delay ability. The results argue for the multidimensionality of the delay construct. PMID- 26828728 TI - GENERALIZED LEARNING CURVES AND THEIR ABILITY AND PERSONALITY CORRELATES. AB - Learning studies have typically been analyzed using the mean learning our across trials. This study was designed to determine if probability learning dab could be described by a family of learning ewes and to identify ability and personality correlates of these curves. One hundred eighteen Ss participated in an 18-trial four-choice probability learning task. The intertribal matrix of intercorrelations was factored to ob6ain three reference lemming curves and the corresponding reference curve scores. Ability and personality variables correlated differentially with these scores. These results and others are discussed. PMID- 26828726 TI - Decreased Expression of a Gene Caused by a T-DNA Insertion in an Adjacent Gene in Arabidopsis. AB - ALADIN is a component of the nuclear pore complex in higher eukaryotes. An Arabidopsis knockout line that had a T-DNA insertion in the ALADIN gene was defective in plant growth and thylakoid development and had reduced photosynthetic activity resulting from lower chlorophyll accumulation. The mutation appeared to decrease the level of chloroplast RuBisCO subunits and PSBA and PGL35 proteins. Unexpectedly, the T-DNA insertion in the ALADIN gene decreased the expression of the neighboring gene PSRP5, which functions in translation in chloroplasts. The mutant phenotype was rescued by expressing PSRP5, but not by expressing ALADIN. The abnormal phenotypes were also detected in an artificial microRNA (amiRNA)-mediated PSRPS5 knockdown, but not in an amiRNA-mediated ALADIN knockdown line. Thus, users of T-DNA insertions should be aware that a T-DNA insertion in one gene can have effects on the expression of neighboring genes. PMID- 26828729 TI - THE RELATIONSHIP OF LIKING AND CHOICE TO ATTRIBUTES OF AN ALTERNATIVE AND THEIR SALIENCY. AB - Evaluations of specific attributes of a subcompact automobile were combined in linear regressions to predict overall liking and purchase intention. Of two forms raw scales and scales weighted by the importance attached to each attribute by each subject-unweighted evaluations proved more consistent and important predictors than did these same evaluations weighted by their saliency. PMID- 26828730 TI - A COMPARISON BETWEEN THE STRUCTURES OF DIVERGENT PRODUCTION ABILITIES OF CHILDREN AT TWO LEVELS OF INTELLECTUAL FUNCTIONINg. AB - Twelve divergent production tests were administered to 46 adolescents whose average WISC full scale IQ was 69.5 and t o a similar group of 48 adolescents whose average WISC full scale IQ was 104.6. Six divergent production factors were extracted in each group and rotated t o a target derived from Guilford's Structure of Intellect Model. In general the subnormal group produced a better fit to the hypothesized structure than the normal group, although the results from the normal group were not considered to be unsupportive of Guilford's theory. PMID- 26828731 TI - A FACTOR ANALYSIS OF SOME MEASURES OF COGNITIVE STYLE. AB - Twenty-six test variables for psychological differentiation and cognitive abilities were factor analyzed with a View towards replication of certain factors of perceptual and conceptual differentiation and relating these factors the cognitive abilities. Eight factors were recovered and interpreted, including Form and Element Articulation, Flexibility of Closure, Speed of Closure, Perceptual Speed, and Conceptual Differentiation in Categorbation. Form Articulation appeared to be more related to Flexibility and Speed of Closure, while Element Articulation was more related to Conceptual Differentiation in Categorization. These findings are briefly discussed. . PMID- 26828732 TI - AN EMPIRICAL COMPARISON OF THE ACCURACY OF SELECTED MULTIVARIATE CLASSIFICATION RULES. AB - This study involved two phases: first, when classification was based on the calibration sample; and second, in a cross-validation setting. Computer generated data were used. Results obtained from rules based on probabilities of group membership were compared for accuracy when classifying in the discriminant space and in the predictor variable spaces. In the first phase accuracy was greater in the predictor variable spaces, while the reverse was true in the second phase. In general, rules based on probabilities of group membership were approximately equally accurate and more accurate than a rule related to a multiple regression analysis. Other findings are also discussed. PMID- 26828734 TI - A GENERALIZED CLASSIFICATION TECHNIQUE USING INTERVAL, ORDINAL, AND NOMINAL VARIABLES. PMID- 26828733 TI - ESTIMATING PROFILE RELIABILITY AND MAXIMALLY RELIABLE COMPOSITES. AB - Two indices of profile reliability (Conger and Lipshitz's canonical reliability, p., and Bock's P) are shown to be equivalent in terms of the individual independent canonical composites; however, because of different weighting procedures, they yield different overall indices of profile reliability. A common formula is provided from which both indices can be derived. Based on Bock's multivariate analysis of variance approach to reliability, sample estimates of profile reliability are derived for Conger and Lipshitz's pp. Because of the frequent lack of parallel forms for profiles, an alternative to the analysis of variance approach is discussed, along with its own inherent problems. In addition, it is shown how maximally reliable independent profile composites can be constructed using either the Bock or Conger and Lipshitz weightings. An example using the WISC for 7 1/2-year olds is provided to illustrate the various techniques. PMID- 26828735 TI - BRIEF REPORT: THE DISTRIBUTION OF PARTIAL CORRELATIONS AND GENERALIZATIONS. AB - The distributional results of regression analysis can be obtained in a simple way through the use of idempotent matrices, as Graybill has shown. An extension of these methods is used to show the relation of the distribution of the partial correlation coefficient to that of the simple correlation. Obvious extensions are given to partial multiple and partial canonical correlations. PMID- 26828741 TI - Decoding four different sound-categories in the auditory cortex using functional near-infrared spectroscopy. AB - The ability of the auditory cortex in the brain to distinguish different sounds is important in daily life. This study investigated whether activations in the auditory cortex caused by different sounds can be distinguished using functional near-infrared spectroscopy (fNIRS). The hemodynamic responses (HRs) in both hemispheres using fNIRS were measured in 18 subjects while exposing them to four sound categories (English-speech, non-English-speech, annoying sounds, and nature sounds). As features for classifying the different signals, the mean, slope, and skewness of the oxy-hemoglobin (HbO) signal were used. With regard to the language-related stimuli, the HRs evoked by understandable speech (English) were observed in a broader brain region than were those evoked by non-English speech. Also, the magnitudes of the HbO signals evoked by English-speech were higher than those of non-English speech. The ratio of the peak values of non-English and English speech was 72.5%. Also, the brain region evoked by annoying sounds was wider than that by nature sounds. However, the signal strength for nature sounds was stronger than that for annoying sounds. Finally, for brain-computer interface (BCI) purposes, the linear discriminant analysis (LDA) and support vector machine (SVM) classifiers were applied to the four sound categories. The overall classification performance for the left hemisphere was higher than that for the right hemisphere. Therefore, for decoding of auditory commands, the left hemisphere is recommended. Also, in two-class classification, the annoying vs. nature sounds comparison provides a higher classification accuracy than the English vs. non-English speech comparison. Finally, LDA performs better than SVM. PMID- 26828740 TI - Bilateral cochlear implants in children: Effects of auditory experience and deprivation on auditory perception. AB - Spatial hearing skills are essential for children as they grow, learn and play. These skills provide critical cues for determining the locations of sources in the environment, and enable segregation of important sounds, such as speech, from background maskers or interferers. Spatial hearing depends on availability of monaural cues and binaural cues. The latter result from integration of inputs arriving at the two ears from sounds that vary in location. The binaural system has exquisite mechanisms for capturing differences between the ears in both time of arrival and intensity. The major cues that are thus referred to as being vital for binaural hearing are: interaural differences in time (ITDs) and interaural differences in levels (ILDs). In children with normal hearing (NH), spatial hearing abilities are fairly well developed by age 4-5 years. In contrast, most children who are deaf and hear through cochlear implants (CIs) do not have an opportunity to experience normal, binaural acoustic hearing early in life. These children may function by having to utilize auditory cues that are degraded with regard to numerous stimulus features. In recent years there has been a notable increase in the number of children receiving bilateral CIs, and evidence suggests that while having two CIs helps them function better than when listening through a single CI, these children generally perform worse than their NH peers. This paper reviews some of the recent work on bilaterally implanted children. The focus is on measures of spatial hearing, including sound localization, release from masking for speech understanding in noise and binaural sensitivity using research processors. Data from behavioral and electrophysiological studies are included, with a focus on the recent work of the authors and their collaborators. The effects of auditory plasticity and deprivation on the emergence of binaural and spatial hearing are discussed along with evidence for reorganized processing from both behavioral and electrophysiological studies. The consequences of both unilateral and bilateral auditory deprivation during development suggest that the relevant set of issues is highly complex with regard to successes and the limitations experienced by children receiving bilateral cochlear implants. This article is part of a Special Issue entitled . PMID- 26828742 TI - Biological Processes Discovered by High-Throughput Sequencing. AB - Advances in DNA and RNA sequencing technologies have completely transformed the field of genomics. High-throughput sequencing (HTS) is now a widely used and accessible technology that allows scientists to sequence an entire transcriptome or genome in a timely and cost-effective manner. Application of HTS techniques has led to many key discoveries, including the identification of long noncoding RNAs, microDNAs, a family of small extrachromosomal circular DNA species, and tRNA-derived fragments, which are a group of small non-miRNAs that are derived from tRNAs. Furthermore, public sequencing repositories provide unique opportunities for laboratories to parse large sequencing databases to identify proteins and noncoding RNAs at a scale that was not possible a decade ago. Herein, we review how HTS has led to the discovery of novel nucleic acid species and uncovered new biological processes during the course. PMID- 26828743 TI - Hypocrol A, a new tyrosol derivative from a sponge-derived strain of the fungus Hypocrea koningii. AB - In continuation of our search for new antibacterial and antioxidant metabolites from sponge-derived fungi, one new tyrosol derivative, hypocrol A (1), together with four known congeners, trichodenol B (2), 4-hydroxyphenethyl acetate (3), 4 hydroxyphenethyl tetradecanoate (4) and 1-oleyltyrosol (5), was isolated from the strain Hypocrea koningii PF04. Their planar structures were unequivocally elucidated by spectroscopic methods and comparison with the literature data. All the compounds displayed weak antibacterial activities against Staphylococcus aureus, methicillin-resistant S. aureus and Escherichia coli, whereas compounds 1 and 2 exhibited a moderate antioxidant efficacy in the DPPH (2,2-diphenyl-1 picrylhydrazyl) radical scavenging assay with IC50 values of 48.5 and 97.4 MUg/mL, respectively. PMID- 26828744 TI - Reply to the Letter by Kaya et al. Entitled "Temperature Control Function of the Choroid May Be the Reason for the Increase in Choroidal Thickness During the Acute Phase of Familial Mediterranean Fever". PMID- 26828745 TI - The Anti-Mullerian Hormone Precursor (proAMH) Is Not Converted to the Receptor Competent Form (AMHN,C) in the Circulating Blood of Mice. AB - Anti-Mullerian hormone (AMH) is a gonadal hormone that regulates aspects of male sexual differentiation and ovarian function. AMH is synthesized as the AMH proprotein precursor (proAMH), which is converted to a receptor-binding form (AMHN,C) by proteolytic cleavage. ProAMH appears to be the predominant species in the ovary, whereas AMHN,C is the prevalent form in circulation. The aim of this study was to determine whether cleavage of proAMH occurs before it is released from the gonad or while in circulation. The individual half-lives of the proAMH and AMHN,C were also determined, as this has important implications for understanding the mechanisms of AMH signaling. Recombinant human (rh)-proAMH or rh-AMHN,C was injected iv into mice. AMH levels were analyzed in a series of repeated blood samples using an assay that detects human, but not murine, AMH. The degree of cleavage of injected proAMH was assessed by immunoprecipitation and Western blotting. The elimination half-life curves were biphasic. The fast-phase elimination was estimated at 6 and 11 minutes for rh-proAMH and rh-AMHN,C, respectively. The slow-phase half-life estimates were 2.4 and 3.8 hours for rh proAMH and rh-AMHN,C, respectively. Immunoprecipitation of rh-proAMH 1 hour after injection determined that no detectable conversion of proAMH to AMHN,C was occurring in circulation. The data suggest that the ratio of proAMH to AMHN,C in the circulation is not altered after it is released from the gonads and that the levels of these 2 circulating forms are likely to reflect AMH activity in the gonad. PMID- 26828746 TI - Persistent cAMP Signaling by Internalized LH Receptors in Ovarian Follicles. AB - A crucial event in female reproduction occurs at midcycle, when a LH peak induces the final maturation of ovarian follicles. LH signals via a G protein-coupled receptor selectively expressed in the outermost follicular cell layers. However, how LH signals are relayed inside these cells and finally to the oocyte is incompletely understood. Here, we monitored LH signaling in intact ovarian follicles of transgenic mice expressing a fluorescent cAMP sensor. We found that LH stimulation induces 2 phases of cAMP signaling in all cell layers surrounding the oocyte. Interfering with LH receptor internalization abolished the second, persistent cAMP phase and partially inhibited oocyte meiosis resumption. These data suggest that persistent cAMP signals from internalized LH receptors contribute to transmitting LH effects inside follicle cells and ultimately to the oocyte. Thus, this study indicates that the recently proposed paradigm of cAMP signaling by internalized G protein-coupled receptors is implicated in receptor function and is physiologically relevant. PMID- 26828747 TI - Cooperation control strategies for China's cross-region pollution in a lake basin based on green reduction cost. AB - The cross-region water pollution issue has always been the widespread concern around the world. It becomes especially critical for China due to the imbalance relates to environmental costs that have accompanied rapid growth of economy. Though the government makes great efforts to improve it, the potential for water pollution conflict is still great. We consider the problem of determining combined control strategies for China's cross-region lake pollution based on the environmental green costs. The problem is first formulated as a generalized bilevel mathematical program where the upper level consists in each region that reduces environmental green costs including three parts: the reduction cost, pollution permit trade cost and cost of environment damage, while the lower level is represented by pollution permit equilibrium market. Finally, we take an empirical analysis in Taihu lake. The numerical study shows that the minimum costs of both total and regional are obviously superior to the current processing costs, which provides theoretical basis for the price of emission permits. IMPLICATIONS: Today, China's rapid gross domestic product (GDP) growth has come at a very high cost, as real estate prices have skyrocketed, the wealth gap has widened, and environmental pollution has worsened. China's central government is urged to correct the GDP-oriented performance evaluation system that is used to judge administrative region leaders. The cross-region water pollution issue has become a troubling issue that urgently needs to be resolved in China. This paper will not only actively aid efforts to govern Lake Taihu and other cross-region valleys, but it will also provide a supplement for theoretical research on cross region pollution issues. PMID- 26828748 TI - Predictive value of Galectin-3 for the occurrence of coronary artery disease and prognosis after myocardial infarction and its association with carotid IMT values in these patients: A mid-term prospective cohort study. AB - OBJECTIVE: The role of Galectin-3(Gal-3) in atherosclerosis progression has not been definitely acknowledged. The aim of the study was to establish the following: whether Gal-3 may act as an independent risk factor of coronary artery disease (CAD) occurrence and its advancement, if Gal-3 has potential relations with classical and new markers of cardiovascular risk (carotid intima-media thickness (cIMT), and whether Gal-3 may be a marker of mortality in the group of patients with myocardial infarction (MI) during mid-term follow-up. PATIENTS AND METHODS: The study group was composed of 233 patients with MI and 100 patients with a stable CAD. Selected risk factors were assessed, Gal-3 concentrations and cIMT were measured. The control group was composed of 100 healthy individuals. RESULTS: In the study group (MI and CAD patients) Gal-3 concentration was significantly higher than in the controls--median 7.9 ng/ml (p = 0.0001) and 10.7 ng/ml (p = 0.00001) vs. 5.5 ng/ml, respectively. Patients with 3-vessel disease had higher levels of Gal-3 than patients with 1-or 2-vessel disease (9.2 ng/ml vs 7.4 ng/ml, p = 0.003). In the group of MI patients who died during the follow-up (average period - 2.8 years), we found a significantly higher concentration of Gal-3 (20.0 ng/ml vs 8.0 ng/ml, p = 0.0005) and cIMT values (common carotid artery(CCA): 1.4 +/- 0.4 mm vs. 1.0 +/- 0.3 mm, p = 0.03; carotid bulb(CB): 2.3 +/- 0.5 mm vs. 1.9 +/- 0.4 mm, p = 0.009). In the model of multivariate logistic regression analysis, the variables influencing the mortality after MI during follow-up were: age>65 years, Gal-3 concentration>8.7 ng/ml, IMT values and plaque occurrence in CB, previous MI and EF<40%. CONCLUSIONS: Gal-3 is an independent risk factor of CAD occurrence, but cIMT values are better markers of CAD advancement. Both Gal-3 concentration>8.7 ng/ml and IMT values in CB were an independent predictive indicators of increased risk of all-cause mortality in patients after MI during mid-term follow up. PMID- 26828749 TI - The effect of statins on valve function and calcification in aortic stenosis: A meta-analysis. AB - BACKGROUND: Aortic calcification has been shown to share the same risk factors as atherosclerosis which suggested a potential benefit from statins therapy. In view of the existing conflicting results, we aimed to provide objective evidence on the effect of statins in aortic stenosis (AS). METHODS AND RESULTS: A meta analysis of eligible studies that used statins in AS was performed. Fourteen studies were identified, 5 randomized controlled trials (RCTs) and 9 observational studies. In the 14 studies as a whole, no significant differences were found in all cause mortality (OR = 0.98, p = 0.91), cardiovascular mortality (OR = 0.80, P = 0.23) or the need for valve replacement (OR = 0.93, p = 0.45) between the statins and the control groups. LDL-cholesterol dropped in the statins groups in both <24 months and >= 24 months follow-up (p < 0.001 for both) but not in controls (p = 0.35 and p = 0.33, respectively). In the <24 months statins group, the annual increase in peak aortic velocity and peak gradient was less (p < 0.0001 and p = 0.004, respectively), but the mean gradient, valve area and calcification score were not different from controls. In the >= 24 months statins group, none of the above parameters was different from controls. CONCLUSIONS: Despite the consistent beneficial effect of statins on LDL cholesterol levels, the available evidence showed no effect on aortic valve structure, function or calcification and no benefit for clinical outcomes. PMID- 26828750 TI - Myeloid interferon-gamma receptor deficiency does not affect atherosclerosis in LDLR(-/-) mice. AB - BACKGROUND AND AIMS: Atherosclerosis is a chronic lipid-driven inflammatory disease of the arterial wall. Interferon gamma (IFNgamma) is an important immunomodulatory cytokine and a known pro-atherosclerotic mediator. However, cell specific targeting of IFNgamma or its signaling in atherosclerosis development has not been studied yet. As macrophages are important IFNgamma targets, we here addressed the involvement of myeloid IFNgamma signaling in murine atherosclerosis. METHODS: Bone marrow was isolated from interferon gamma receptor 2 chain (IFNgammaR2) wildtype and myeloid IFNgammaR2 deficient mice and injected into lethally irradiated LDLR(-/-) mice. After recovery mice were put on a high fat diet for 10 weeks after which atherosclerotic lesion analysis was performed. In addition, the accompanying liver inflammation was assessed. RESULTS: Even though absence of myeloid IFNgamma signaling attenuated the myeloid IFNgamma response, no significant differences in atherosclerotic lesion size or phenotype were found. Also, when examining the liver inflammatory state no effects of IFNgammaR2 deficiency could be observed. CONCLUSION: Overall, our data argue against a role for myeloid IFNgammaR2 in atherosclerosis development. Since myeloid IFNgamma signaling seems to be nonessential throughout atherogenesis, it is important to understand the mechanisms by which IFNgamma acts in atherogenesis. In the future new studies should be performed considering other cell-specific targets. PMID- 26828751 TI - The relation between coronary tortuosity and calcium score in patients with chronic stable angina and normal coronaries by CT angiography. AB - PURPOSE: Coronary tortuosity (CorT) is a phenomenon often noticed by cardiologists and may be associated with stable angina even without significant lesion. We aim to determine the relationship between CorT and coronary artery calcium (CAC) scoring in patients with chronic stable angina and normal or near normal coronaries detected by computed tomography (CT) angiography. METHODS: This is a cross sectional retrospective study included all patients with stable angina underwent CT coronary angiography and calcium scoring that reveals normal or non significant coronary artery lesion. The presence of CorT was revised. CorT is defined as a fixed >= 3 bends during both systole and diastole, with each bend >= 45 degrees . RESULTS: The study involved 83 patients. CT angiography revealed 31 patients (37.3%) with tortuous one or more coronary arteries and 52 patients (62.7%) without any CorT. The patients were divided into 2 groups; those patients with tortuous coronary arteries (CorT group) and those without coronary tortuosity (N CorT group). There was no significant difference between both groups regarding age, presence of DM, and dyslipidemia. However, there was a highly significant difference between both groups regarding hypertension with more hypertension among the CorT group (p value < 0.001). There was a significant difference between both groups in CAC score with high CAC score in the CorT group (p value < 0.05). There was significant correlation between CorT and CAC score (unadjusted p = 0.06); if adjusted for co-variated affecting CorT (p = 0.022). CONCLUSION: CorT is associated with subclinical atherosclerosis and increased CAC score even in the absence of significant obstructive lesion. PMID- 26828752 TI - Why the radial augmentation index is low in patients with diabetes: The J-HOP study. AB - BACKGROUND: Radial augmentation index (rAI), a marker of aortic wave reflection, is usually lower in patients with diabetes (DM) than in non-DM subjects, even though atherosclerotic change is advanced in DM. OBJECTIVE: We sought to explore why rAI in DM is lower than in non-DM. METHODS: We performed radial applanation tonometry in 1787 subjects who had at least one cardiovascular risk factor. The rAI was defined as [late systolic shoulder pressure amplitude (PP2)]/[radial pulse pressure (rPP)]. The late systolic shoulder blood pressure (SBP2) and PP2 of a radial pressure wave were used as estimates of the central SBP and PP (cPP), respectively. RESULTS: The age (65.8 +/- 9.8 vs. 65.8 +/- 12.1 yrs) and mean brachial SBP (141 +/- 16 vs. 141 +/- 17 mmHg) were similar between the DM and non DM groups. The rAI was significantly lower in the DM group (83.3 +/- 14.1 vs. 87.3 +/- 15.7%, p < 0.001), but clinic PP (62 +/- 14 vs. 59 +/- 14 mmHg, p < 0.001) and cPP (51 +/- 15 vs. 49 +/- 15 mmHg, p = 0.019) were significantly greater in the DM group than in the non-DM group. In multivariable analyses adjusting for covariates, the significant determinants of rAI were the estimated glomerular filtration rate (eGFR) (beta = 0.17, p < 0.001) in the DM group, and the log-transformed homeostatic model assessment of insulin resistance (HOMA-IR) (beta = -0.15, p < 0.001) in the non-DM group. The same trends were also seen for central SBP and cPP. CONCLUSIONS: The lower rAI in DM associated with higher cPP compared to non-DM suggests proximal conduit-predominant arterial stiffening causing reduced reflection coefficients at systemic reflection sites. As renal function decreases, a cPP increase may overcome the increase of augmentation pressure in the DM group. PMID- 26828753 TI - Facilitatory effects of fetuin-A on atherosclerosis. AB - OBJECTIVE: Fetuin-A is a circulating glycoprotein that is produced by liver and adipose tissue. Fetuin-A is known to induce insulin resistance and suppress vascular calcification. There are conflicting reports that show increased or decreased serum fetuin-A levels in patients with coronary artery disease (CAD). Since the role of fetuin-A in atherosclerosis remains still controversial, we aimed to clarify it in this study. METHODS: We investigated the expression of fetuin-A in atheromatous plaques in CAD patients and restenosis lesions in balloon-injured rat carotid arteries in vivo. We also assessed in vitro effects of fetuin-A on inflammatory molecules in human umbilical vein endothelial cells (HUVECs), oxidized low-density lipoprotein-induced foam cell formation in human monocyte-derived macrophages, and the migration, proliferation, and extracellular matrix expression in human aortic smooth muscle cells (HASMCs) in a serum-free culture system. RESULTS: Fetuin-A was abundantly expressed in cultured human monocytes, macrophages, fibroblasts, HASMCs, and human coronary artery SMCs, atheromatous plaques in human coronary arteries, and restenosis lesions in rat carotid arteries. In vitro experiments showed that fetuin-A stimulated interleukin-6, monocyte chemotactic protein-1, intercellular adhesion molecule-1, and E-selectin expression in HUVECs. Fetuin-A enhanced macrophage foam cell formation associated with scavenger receptors (CD36 and SR-A) and acyl CoA:cholesterol acyltransferase-1 up-regulation and ATP-binding cassette transporter A1 down-regulation, and increased cell proliferation and collagen-1 and -3 expression via PI3K/AKT/c-Src/NF-kappaB/ERK1/2 pathways in HASMCs. CONCLUSION: Our results indicate that fetuin-A exerts the stimulatory effects on inflammatory responses in HUVECs, macrophage foam cell formation, and proliferation and collagen production in HASMCs, leading to the development of atherosclerosis. PMID- 26828755 TI - Polymorphisms in NRGN are associated with schizophrenia, major depressive disorder and bipolar disorder in the Han Chinese population. AB - BACKGROUND: The NRGN gene locates on 11q24 and encodes a postsynaptic protein kinase substrate that binds calmodulin in the absence of calcium. In a previous genome-wide association study of schizophrenia in the Caucasian population, rs12807809 of NRGN was found to be significantly associated with schizophrenia, moreover, it was further found to be associated with bipolar disorder. METHODS: We recruited 1248 schizophrenia cases, 1344 bipolar disorder cases, 1056 major depressive disorder cases, and 1248 healthy controls from Han Chinese population. Rs12807809 and another two tag SNPs of NRGN were genotyped and analyzed in three diseases respectively. A meta-analysis of rs12807809 was also conducted to verify its association with schizophrenia in Han Chinese population. RESULTS: Rs7113041 was associated with bipolar disorder (odds ratio, 95% confidence interval (OR, 95% CI)=1.194, 1.032-1.383; Pgenotype=0.0126), and rs12278912 was associated with major depressive disorder (OR, 95% CI=0.789, 0.673-0.924; Pallele=0.0102, Pgenotype=0.0399) after Bonferroni correction. The "GA" haplotype of rs7113041 rs12278912 was significantly associated with schizophrenia, major depressive disorder and bipolar disorder (corresponding P values were 2.85E-04, 3.00E-03, and 5.40E-04 after Bonferroni correction). LIMITATIONS: Despite the association between NRGN and psychoses we have found, we failed to validate the positive variant rs12807809, which was reported in the Caucasian genome-wide association study both in our single site association test and the meta-analysis. Functional studies are needed to illuminate the role of NRGN in the pathogenesis of these mental disorders. CONCLUSIONS: Our findings prove that NRGN is a shared susceptibility gene of schizophrenia, major depression and bipolar disorder in Han Chinese, and this might provide a new target for the diagnosis and treatment of these mental disorders. PMID- 26828756 TI - Groups 4 Health: Evidence that a social-identity intervention that builds and strengthens social group membership improves mental health. AB - BACKGROUND: Social isolation and disconnection have profound negative effects on mental health, but there are few, if any, theoretically-derived interventions that directly target this problem. We evaluate a new intervention, Groups 4 Health (G4H), a manualized 5-module psychological intervention that targets the development and maintenance of social group relationships to treat psychological distress arising from social isolation. METHODS: G4H was tested using a non randomized control design. The program was delivered to young adults presenting with social isolation and affective disturbance. Primary outcome measures assessed mental health (depression, general anxiety, social anxiety, and stress), well-being (life satisfaction, self-esteem) and social connectedness (loneliness, social functioning). Our secondary goal was to assess whether mechanisms of social identification were responsible for changes in outcomes. RESULTS: G4H was found to significantly improve mental health, well-being, and social connectedness on all measures, both on program completion and 6-month follow-up. In line with social identity theorizing, analysis also showed that improvements in depression, anxiety, stress, loneliness, and life satisfaction were underpinned by participants' increased identification both with their G4H group and with multiple groups. LIMITATIONS: This study provides preliminary evidence of the potential value of G4H and its underlying mechanisms, but further examination is required in other populations to address issues of generalizability, and in randomized controlled trials to address its wider efficacy. CONCLUSIONS: Results of this pilot study confirm that G4H has the potential to reduce the negative health-related consequences of social disconnection. Future research will determine its utility in wider community contexts. PMID- 26828754 TI - microRNAs in lipoprotein metabolism and cardiometabolic disorders. AB - Circulating levels of low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) are two of the most important risk factors for the development of cardiovascular disease (CVD), the leading cause of death worldwide. Recently, miRNAs have emerged as critical regulators of cholesterol metabolism and promising therapeutic targets for the treatment of CVD. A great deal of work has established numerous miRNAs as important regulators of HDL metabolism. This includes miRNAs that target ABCA1, a critical factor for HDL biogenesis and reverse cholesterol transport (RCT), the process through which cells, including arterial macrophages, efflux cellular cholesterol for transport to and removal by the liver. The most well studied of these miRNAs, miR-33, has been demonstrated to target ABCA1, as well as numerous other genes involved in metabolic function and RCT, and therapeutic inhibition of miR-33 was found to increase HDL levels in mice and non-human primates. Moreover, numerous studies have demonstrated the beneficial effects of miR-33 inhibition or knockout on reducing atherosclerotic plaque burden. Even more recent work has identified miRNAs that regulate LDL cholesterol levels, including direct modulation of LDL uptake in the liver through targeting of the LDL receptor. Among these, inhibition of miR-128-1, miR-148a, or miR-185 was found to reduce plasma LDL levels, and inhibition of miR-185 was further demonstrated to reduce atherosclerotic plaque size in ApoE(-/-) mice. Due to their ability to target many different genes, miRNAs have the ability to mediate complex physiologic changes through simultaneous regulation of multiple interrelated pathways. Of particular importance for CVD, inhibition of miR-148a may prove an important therapeutic approach for combating dyslipidemia, as this has been demonstrated to both raise plasma HDL levels and lower LDL levels in mice by targeting both ABCA1 and LDLR, respectively. In this review we highlight recent advances in our understanding of how miRNAs regulate cholesterol metabolism and the development of atherosclerotic plaques and discuss the potential of anti-miRNA therapies for the treatment and prevention of CVD. PMID- 26828757 TI - Particle Pollution Estimation Based on Image Analysis. AB - Exposure to fine particles can cause various diseases, and an easily accessible method to monitor the particles can help raise public awareness and reduce harmful exposures. Here we report a method to estimate PM air pollution based on analysis of a large number of outdoor images available for Beijing, Shanghai (China) and Phoenix (US). Six image features were extracted from the images, which were used, together with other relevant data, such as the position of the sun, date, time, geographic information and weather conditions, to predict PM2.5 index. The results demonstrate that the image analysis method provides good prediction of PM2.5 indexes, and different features have different significance levels in the prediction. PMID- 26828758 TI - Speech rhythm sensitivity and musical aptitude: ERPs and individual differences. AB - This study investigated the electrophysiological markers of rhythmic expectancy during speech perception. In addition, given the large literature showing overlaps between cognitive and neural resources recruited for language and music, we considered a relation between musical aptitude and individual differences in speech rhythm sensitivity. Twenty adults were administered a standardized assessment of musical aptitude, and EEG was recorded as participants listened to sequences of four bisyllabic words for which the stress pattern of the final word either matched or mismatched the stress pattern of the preceding words. Words with unexpected stress patterns elicited an increased fronto-central mid-latency negativity. In addition, rhythm aptitude significantly correlated with the size of the negative effect elicited by unexpected iambic words, the least common type of stress pattern in English. The present results suggest shared neurocognitive resources for speech rhythm and musical rhythm. PMID- 26828759 TI - Natural history and management of refractory benign esophageal strictures. AB - BACKGROUND AND AIMS: The natural history of refractory benign esophageal strictures (RBES) is unclear, and surgery or percutaneous endoscopic gastrostomy (PEG) may be the only viable long-term options. The aim of the present study was to assess the long-term outcomes of patients with RBES. METHODS: Clinical data of consecutive patients with RBES treated in the previous 15 years in 2 tertiary care referral academic centers with specialized interest in esophageal stricture management were retrospectively analyzed. RBES was defined as the persistence and/or recurrence of dysphagia despite at least 5 dilation sessions and/or cycles with dilation to at least 14 mm. Information regarding the use of dilation or stents and the dysphagia-free period between subsequent interventions and adverse events was collected. Clinical success was defined as no need for endoscopic interventions for at least 6 months; unfavorable outcomes were defined as the need for endoscopic treatment at the end of follow-up, surgery, or percutaneous endoscopic gastrostomy (PEG). Predictors of unfavorable outcomes were assessed by multivariate analysis. A linear mixed-effect model was used to measure dysphagia free period changes over time. RESULTS: Overall, 70 patients with RBES (46 male; mean age 60 years) were followed for a mean of 43.9 months (range 3.7-157 months). Caustic, postradiotherapy, surgical, mixed, and postinflammatory etiology accounted for 10%, 14.3%, 31.4%, 40%, and 4.3% of causes, respectively. All patients underwent sequential sessions of pneumatic or bougie dilation, with a median of 15.5 dilation sessions per patient. Self-expandable metal stents (SEMSs) and biodegradable stents were placed in 18 (25.7%) and 14 (20%) patients, respectively. RBES resolution was achieved in only 22 of 70 (31.4%) patients. Two deaths (3%) were related to RBES. The success rate was lower in those who also were treated with endoprosthetics (odds ratio [OR] 3.7; 95% confidence interval [CI], 1.01-18.0). The mean dysphagia-free period was 3.3 months (95% CI, 2.4-4.1) for patients treated with dilation and 2.4 months (95% CI, 1.2-3.6) for those treated with stents (P = .062). Over time, the total dysphagia-free period increased at a rate of 4.1 days (95% CI, 1.7-6.4) per dilation. There was no difference in the rate of change across groups defined by sex (P = .976), age (P = .633), or endoscopic treatment (P = .267). CONCLUSIONS: Our multicenter series showed a disappointing long-term outcome for RBES, with only 1 of 3 achieving clinical resolution. The dysphagia-free period was relatively short, affecting the quality of life. Endoprosthetics did not appear to affect the natural history of RBES. PMID- 26828761 TI - Endoscopic submucosal multi-tunnel dissection for circumferential superficial esophageal neoplastic lesions (with videos). AB - BACKGROUND AND AIMS: Endoscopic submucosal tunnel dissection (ESTD) has been used for dissection of large esophageal neoplastic lesions, but there are still some technical problems in treating circumferential superficial esophageal neoplastic lesions. This study aimed to assess the efficacy and safety of endoscopic submucosal multi-tunnel dissection (ESMTD) for circumferential superficial esophageal neoplastic lesions in selected patients followed up for 1 to 12 months. METHODS: From July 2014 to February 2015, the first series of 7 consecutive patients with circumferential superficial esophageal neoplastic lesions underwent ESMTD at our endoscopic center. The macroscopic types were classified according to the Paris endoscopic classification of superficial neoplastic lesions. RESULTS: The average length of lesions was 6.1 cm in 7 selected patients. The operative time ranged from 69 to 169 minutes (mean 121 minutes). En bloc dissection with negative basal margins was achieved in all lesions without serious intraoperative adverse events. Esophageal stricture was observed in all patients 1 to 3 months after the operation and was relieved after a retrievable metal stent was placed or esophageal water balloon dilatation was performed; however, one patient died of cerebral infarction 2 months after ESMTD. CONCLUSIONS: ESMTD is feasible, safe, and effective for the treatment of circumferential superficial esophageal neoplastic lesions in select patients. PMID- 26828760 TI - Adverse events after surgery for nonmalignant colon polyps are common and associated with increased length of stay and costs. AB - BACKGROUND AND AIMS: Endoscopic resection (ER) is a safe and effective treatment for nonmalignant complex colorectal polyps (complex polyps). Surgical resection (SR) remains prevalent despite limited outcomes data. We aimed to evaluate SR outcomes for complex polyps and compare SR outcomes to those of ER. METHODS: We performed a single-center, retrospective, cohort study of all patients undergoing SR (2003-2013) and ER (2011-2013) for complex polyps. We excluded patients with invasive carcinoma from the SR cohort. Primary outcomes were 12-month adverse event (AE) rate, length of stay (LOS), and costs. SR outcomes over a 3-year period (2011-2013) were compared with the overlapping ER cohort. RESULTS: Over the 11-year period, 359 patients (mean [+/- SD] age 64 +/- 11 years) underwent SR (58% laparoscopic) for complex polyps. In total, 17% experienced an AE, and 3% required additional surgery; 12-month mortality was 1%. Including readmissions, median LOS was 5 days (IQR 4-7 days), and costs were $14,528. When an AE occurred, costs ($25,557 vs $14,029; P < .0001) and LOS (11 vs 5 days; P < .0001) significantly increased. From 2011 to 2013, 198 patients were referred for ER, and 73 underwent primary SR (70% laparoscopic). There was a lower AE rate for ER versus primary SR (10% vs 18%; P = .09). ER costs (including rescue SR, when required) were lower than those of primary SR ($2152 vs $15,264; P < .0001). CONCLUSIONS: AEs occur in approximately one-sixth of patients after SR for complex polyps. ER-accounting for rescue SR caused by malignancy, AEs, or incomplete resection-is associated with markedly lower costs than SR. These data should be used when counseling patients about treatment options for complex polyps. PMID- 26828762 TI - Biaryl amide compounds reduce the inflammatory response in macrophages by regulating Dectin-1. AB - Macrophages are archetypal innate immune cells that play crucial roles in the recognition and phagocytosis of invading pathogens, which they identify using pattern recognition receptors (PRRs). Dectin-1 is essential for antifungal immune responses, recognizing the fungal cellular component beta-glucan, and its role as a PRR has been of increasing interest. Previously, we discovered and characterized a novel biaryl amide compound, MPS 03, capable of inhibiting macrophage phagocytosis of zymosan. Therefore, in this study we aimed to identify other biaryl amide compounds with greater effectiveness than MPS 03, and elucidate their cellular mechanisms. Several MPS 03 derivatives were screened, four of which reduced zymosan phagocytosis in a similar manner to MPS 03. To establish whether such phagocytosis inhibition influenced the production of inflammatory mediators, pro-inflammatory cytokine and nitric oxide (NO) levels were measured. The production of TNF-alpha, IL-6, IL-12, and NO was significantly reduced in a dose-dependent manner. Moreover, the inflammation-associated MAPK signaling pathway was also affected by biaryl amide compounds. To investigate the underlying cellular mechanism, PRR expression was measured. MPS 03 and its derivatives were found to inhibit zymosan phagocytosis by decreasing Dectin-1 expression. Furthermore, when macrophages were stimulated by zymosan after pretreatment with biaryl amide compounds, downstream transcription factors such as NFAT, AP-1, and NF-kappaB were downregulated. In conclusion, biaryl amide compounds reduce zymosan-induced inflammatory responses by downregulating Dectin 1 expression. Therefore, such compounds could be used to inhibit Dectin-1 in immunological experiments and possibly regulate excessive inflammatory responses. PMID- 26828763 TI - Beneficial effects of ellagic acid against animal models of scopolamine- and diazepam-induced cognitive impairments. AB - Context In a previous study, it has been shown that ellagic acid (EA), a polyphenolic compound found in pomegranate and different berries, prevents cognitive and hippocampal long-term potentiation (LTP) impairments induced by traumatic brain injury in rats through antioxidant and anti-inflammatory mechanisms. Objective The present study was conducted to assess the potential of EA as a memory enhancer. Materials and methods The elevated plus maze (EPM) and passive avoidance (PA) paradigm were used to evaluate learning and memory parameters. Three doses (10, 30 and 100 mg/kg, i.p.) of EA were administered to animals. Memory impairment was induced by scopolamine treatment (0.4 mg/kg, i.p.) and/or diazepam (1 mg/kg, i.p.). Acquisition trials were carried out 30 min after scopolamine treatment and retention trials were performed for 5 min 24 h after the acquisition trials. Results EA at doses 30 and 100 mg/kg significantly reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) in the EPM and PA tests in mice. Also, EA at doses 30 and 100 mg/kg significantly antagonized the amnesia induced by diazepam (1 mg/kg, i.p.) in EPM test in rats. Moreover, chronic administration of EA at dose 30 mg/kg ameliorated the memory deficit induced by diazepam (1 mg/kg, i.p.) in rats. Discussion and conclusion This study demonstrates that ellagic acid is effective in preventing scopolamine- and diazepam-induced cognitive impairments without altering the animals' locomotion. This suggests the potential of EA application as a useful memory restorative agent in the treatment of dementia seen in elderly persons. PMID- 26828764 TI - Armbrust et al. 2015: Randomization questionable. PMID- 26828765 TI - Resisting resistance: Establishing new treatment options for CRPC patients. AB - Overcoming drug resistance in castrate resistant prostate cancer requires improved understanding of mechanisms by which resistance occurs, as well as new treatment options. A recent study published in Nature (Li et al. 2015) examines the mechanism of abiraterone activity, and reveals the bioactivity of a breakdown product with exciting repercussions for therapy regimes. PMID- 26828766 TI - Trends in Biobanking: A Bibliometric Overview. AB - Biobanks have become indispensable tools for a wide array of life and environmental sciences, and biotechnology. To evaluate trends in biobanking, 20,000 bibliographic records were retrieved and analyzed between 1939 and 2014 from the Scopus database using a series of biobank-related search terms within titles and keywords. Since the 1990s, the field of biobanking has been, and still is, experiencing above-average growth in terms of publications, journals, and thematic orientations. Almost two-thirds of all indexed biobanking documents have been published in the last decade, with now >1,000 publications in 600 distinct journals per year. Around 50,000 individual authors can be identified who have so far contributed to the field of biobanking, with an average of 1.5 publications per author. Author affiliations follow an uneven distribution: 42% of the authors are based in Europe, 33% in North America, 13% in Asia, 5% in South America, 4% in Australasia, and 2% in Africa. Analyzing the most common title words revealed (as did the journals) a strong focus on blood banking, but other biospecimen types-especially seeds, cells, and tissues-have been gaining increasing weight recently. Among medical applications, transfusion dominates, followed by transplantation. While a noticeable increase in disease and especially health occurred at the beginning of the millennium, cohort and consent seem to have become high-relevance topics only in this decade. In terms of banked organisms, human dominates, followed by viruses and plants (especially represented through seed banking). A very rough estimate based on subject categories suggests that a third of all publications in biobanking focus on organisms other than humans. However, animal, fungal, and microbial biobanking are still underrepresented, especially when considering their shares in global biodiversity. PMID- 26828767 TI - Long-Term Outcomes of Simultaneous Liver-Kidney Transplant Patients with Hepatitis B Compared to with Liver Transplant Alone. AB - BACKGROUND: The number and survival rate of simultaneous liver-kidney transplant (SLKT) recipients have increased dramatically since 2002. However, the long-term effectiveness of SLKT in patients with hepatitis B is unknown. MATERIAL/METHODS: Forty-six patients who visited the Organ Transplant Center of the Shanghai First People's Hospital between January 2001 and May 2005 had hepatitis B virus infection and renal failure (any degree), and underwent organ transplantation: 21 patients underwent SLKT and 25 patients underwent liver transplant (LT) alone. RESULTS: The 1-, 3-, and 5-year survival rates of SLKT recipients were 90.5%, 81.0%, and 81.0%, respectively. Incidence of acute hepatic allograft rejection between SLKT recipients and LT recipients (33% vs. 16%) did not reach significance (P=0.170). Despite higher infection rate, more prevalent hepatitis B relapse, and longer stay in the intensive care unit, SLKT recipients experienced significantly higher 1-year survival rate (90.5%) compared with LT recipients (60%, P=0.019). Multivariate regression analysis revealed that postoperative renal failure (odds ratio (OR)=48, P=0.003) and Risk/Injury/Failure/Loss/End stage (RIFLE) stage (OR=8, P=0.012) were independent risk factors for postoperative death after LT. CONCLUSIONS: SLKT in patients with hepatitis B had higher early-stage infection rate, but had a higher long-term survival rate compared with the LT group. Although the incidence of postoperative hepatitis B relapse in SLKT recipients was higher, timely and reasonable treatment can ensure long-term survival of patients. Worsening RIFLE stage of recipients can predict high mortality when only given LT. SLKT might be a better choice for RIFLE stage 2 or 3 patients than LT alone. PMID- 26828768 TI - Fatigue limit of polycrystalline zirconium oxide ceramics: Effect of grinding and low-temperature aging. AB - The following study aimed to evaluate the effect of grinding and low-temperature aging on the fatigue limit of Y-TZP ceramics for frameworks and monolithic restorations. Disc specimens from each ceramic material, Lava Frame (3M ESPE) and Zirlux FC (Ivoclar Vivadent) were manufactured according to ISO:6872-2008 and assigned in accordance with two factors: (1) "surface treatment"-without treatment (as-sintered, Ctrl), grinding with coarse diamond bur (181um; Grinding); and (2) "low-temperature aging (LTD)" - presence and absence. Grinding was performed using a contra-angle handpiece under constant water-cooling. LTD was simulated in an autoclave at 134 degrees C under 2-bar pressure for 20h. Mean flexural fatigue limits (20,000 cycles) were determined under sinusoidal loading using stair case approach. For Lava ceramic, it was observed a statistical increase after grinding procedure and different behavior after LTD stimuli (Ctrl= 30 degrees was computed from accelerometer recordings for several consecutive days during work, categorized into long (highest tertile) and short-moderate (remaining tertiles) duration. LBPi was measured on a 0-10 scale and categorized into low (<= 5) and high (>5) pain. Self-reported social support was categorized into low, moderate, and high levels. Multi-adjusted logistic regressions estimated the association between forward bending and LBPi and the effect modification by social support. RESULTS: Forward bending and LBPi were not significantly associated but modified by social support. Workers with low social support and long duration of forward bending had higher likelihood of high LBPi [odds ratio (OR) 2.97, 95% confidence interval (95% CI) 1.11-7.95] compared to workers with high social support and long duration of forward bending. Among workers with low social support, workers with long duration of forward bending had higher likelihood of high LBPi (OR 3.28, 95% CI 0.99-10.90) compared to workers with short-moderate duration of forward bending. Among workers with high social support, workers with long duration of forward bending had reduced likelihood of high LBPi (OR 0.39, 95% CI 0.16-0.95) compared to workers with short-moderate duration of forward bending. CONCLUSIONS: Social support modifies the association between objectively measured forward bending and LBPi among blue collar workers. PMID- 26828771 TI - Linker-Induced Structural Diversity and Photophysical Property of MOFs for Selective and Sensitive Detection of Nitroaromatics. AB - The linker [1,1':3',1"-terphenyl]-4,4',4",6'-tetracarboxylic acid (H4L) was used to construct two three-dimensional (3D) metal-organic frameworks (MOFs), namely, {[Cd2(L)(L1)(DMF)(H2O)](2DMF)(3H2O)}n (1) and {[Cd4(L)2(L2)3(H2O)2](8DMF)(8H2O)}n (2) (DMF = N,N'-dimethylformamide) in the presence of colinkers 4,4'-bipyridine (L1) and 2-amino-4,4'-bipyridine (L2), respectively, under solvothermal condition. A small change in the colinker leads to significant differences in the overall structure of the MOFs. Topological analysis reveals that the framework 1 exhibits 6,4-connected forbidden sub-configuration (FSC) topology, while the framework 2 exhibits twofold interpenetrated and (3,4,4)-connected new network topology with Schlafli point symbol {4.6(2)}{4.6(4).8}{4(2).6(2).8(2)}. The crystallographic investigation reveals the framework 2 having single helix structure, which is further coiled through noncovalent interaction, afforded a double-helix structure similar to DNA. These double helices are further connected through the colinker L2 to form an overall 3D structure. Besides framework 2 exhibits remarkable fluorescence intensity compared to 1. Framework 2 displayed a strong emission at 457 nm when a sample of 2 was dispersed in ethanol and excited at 334 nm. This emission is selectively and completely quenched in the presence of 2,4,6-trinitrophenol (TNP) allowing its detection in the presence of other nitroaromatic compounds. The quenching constant for TNP was found to be 3.89 * 10(4) M(-1), which is 26 times higher than that of TNT demonstrating greater and selective quenching ability. The emission is restored to its original value when the sample after collected by filtration is dispersed in fresh ethanol for 1 d. Interestingly, when solid 2 is exposed to different nitroaromatic compounds, its emission is quenched selectively in the presence of nitrobenzene. In this case, the emission is restored upon heating the sample to 150 degrees C for 2 h. PMID- 26828770 TI - Treatment Attendance Among Veterans With Depression, Substance Use Disorder, and Trauma. AB - OBJECTIVE: Low attendance in psychotherapy, particularly among individuals with comorbid disorders, is a pervasive challenge. The present study examined predictors of treatment attendance in a sample of veterans with depression, substance use disorder, and trauma. METHODS: This is an analysis of data collected as part of a larger clinical trial involving outpatients at a Veterans Administration dual diagnosis clinic. Individuals were excluded if they had significant memory deficits, schizophrenia, bipolar disorder, or substantial travel constraints. Participants (N = 146) received 12 weeks of group-delivered integrated cognitive behavioral therapy for depression and substance use, followed by randomization to 12 additional weeks of individually delivered cognitive behavioral therapy (n = 62) or cognitive processing therapy (n = 61) modified to address substance use and trauma. Participants, therapists, and researchers were not blinded to group assignment. For this study, we included only the 123 participants who were randomized into the second phase, analyzing predictors of treatment attendance categorized into predisposing factors, enabling factors, and need factors. RESULTS: Participants were primarily male (89%) and Caucasian (76%) and averaged 47 years old (SD = 12). Forty-four percent had alcohol use disorder, 16% had drug use disorder, and 40% had polysubstance use disorder. Most met criteria for PTSD (82%), with 44% having combat-related trauma, 33% sexual trauma, and 28% other trauma. Treatment attendance did not differ between groups. More education was associated with increased group (r = .19, p = .04) and individual session attendance (r = .28, p = .002). Individuals with chronic housing problems attended fewer group sessions (r = -.19, p = .04), while individuals with sexual trauma, compared to those with other traumas, attended more individual sessions (r = .23, p = .01). Number of group sessions attended was positively associated with individual session attendance. CONCLUSIONS: Few variables were significantly predictive of treatment attendance, possibly due to the complex nature of comorbid disorders. Including a focus on trauma was not associated with lower attendance. Special consideration may need to be given to education level, homelessness, and trauma when trying to engage and retain patients with comorbid disorders in treatment. This clinical trial is registered at www.clinicaltrials.gov as NCT00958217. PMID- 26828772 TI - The Quorum Sensing Inhibitor Hamamelitannin Increases Antibiotic Susceptibility of Staphylococcus aureus Biofilms by Affecting Peptidoglycan Biosynthesis and eDNA Release. AB - Treatment of Staphylococcus aureus infections has become increasingly challenging due to the rapid emergence and dissemination of methicillin-resistant strains. In addition, S. aureus reside within biofilms at the site of infection. Few novel antibacterial agents have been developed in recent years and their bacteriostatic or bactericidal activity results in selective pressure, inevitably inducing antimicrobial resistance. Consequently, innovative antimicrobials with other modes of action are urgently needed. One alternative approach is targeting the bacterial quorum sensing (QS) system. Hamamelitannin (2',5-di-O-galloyl-d hamamelose; HAM) was previously suggested to block QS through the TraP QS system and was shown to increase S. aureus biofilm susceptibility towards vancomycin (VAN) although mechanistic insights are still lacking. In the present study we provide evidence that HAM specifically affects S. aureus biofilm susceptibility through the TraP receptor by affecting cell wall synthesis and extracellular DNA release of S. aureus. We further provide evidence that HAM can increase the susceptibility of S. aureus biofilms towards different classes of antibiotics in vitro. Finally, we show that HAM increases the susceptibility of S. aureus to antibiotic treatment in in vivo Caenorhabditis elegans and mouse mammary gland infection models. PMID- 26828773 TI - The developmental origins and lineage contributions of endocardial endothelium. AB - Endocardial development involves a complex orchestration of cell fate decisions that coordinate with endoderm formation and other mesodermal cell lineages. Historically, investigations into the contribution of endocardium in the developing embryo was constrained to the heart where these cells give rise to the inner lining of the myocardium and are a major contributor to valve formation. In recent years, studies have continued to elucidate the complexities of endocardial fate commitment revealing a much broader scope of lineage potential from developing endocardium. These studies cover a wide range of species and model systems and show direct contribution or fate potential of endocardium giving rise to cardiac vasculature, blood, fibroblast, and cardiomyocyte lineages. This review focuses on the marked expansion of knowledge in the area of endocardial fate potential. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID- 26828775 TI - New signal transduction paradigms in anthracycline-induced cardiotoxicity. AB - Anthracyclines, such as doxorubicin, are the most potent and widely used chemotherapeutic agents for the treatment of a variety of human cancers, including solid tumors and hematological malignancies. However, their clinical use is hampered by severe cardiotoxic side effects and cancer therapy-related heart disease has become a leading cause of morbidity and mortality among cancer survivors. The identification of therapeutic strategies limiting anthracycline cardiotoxicity with preserved antitumor efficacy thus represents the current challenge of cardio-oncologists. Anthracycline cardiotoxicity has been originally ascribed to the ability of this class of drugs to disrupt iron metabolism and generate excess of reactive oxygen species (ROS). However, small clinical trials with iron chelators and anti-oxidants failed to provide any benefit and suggested that doxorubicin cardiotoxicity is not solely due to redox cycling. New emerging explanations include anthracycline-dependent regulation of major signaling pathways controlling DNA damage response, cardiomyocyte survival, cardiac inflammation, energetic stress and gene expression modulation. This review will summarize recent studies unraveling the complex web of mechanisms of doxorubicin mediated cardiotoxicity, and identifying new druggable players for the prevention of heart disease in cancer patients. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID- 26828776 TI - Intramolecular Interaction, Photoisomerization, and Mechanical C-C Bond Dissociation of 1,2-Di(9-anthryl)benzene and Its Photoisomer: A Fundamental Moiety of Anthracene-Based pi-Cluster Molecules. AB - We report variable and unique properties of 1,2-di(9-anthryl)benzene 1 as a fundamental moiety of anthracene-based pi-cluster molecules. Due to a through space pi-conjugation between anthracene units, excimer emission at room temperature and charge delocalized state in radical cation state of 1 could be observed. Photoirradiation to 1 afforded an intramolecular [4 + 4] cyclized anthracene dimer 1' having a high strain energy with long C-C bond that exceeded 1.68 A, resulting in C-C bond dissociation by simple mechanical grinding. PMID- 26828777 TI - Fast and Reliable Quantitative Peptidomics with labelpepmatch. AB - The use of stable isotope tags in quantitative peptidomics offers many advantages, but the laborious identification of matching sets of labeled peptide peaks is still a major bottleneck. Here we present labelpepmatch, an R-package for fast and straightforward analysis of LC-MS spectra of labeled peptides. This open-source tool offers fast and accurate identification of peak pairs alongside an appropriate framework for statistical inference on quantitative peptidomics data, based on techniques from other -omics disciplines. A relevant case study on the desert locust Schistocerca gregaria proves our pipeline to be a reliable tool for quick but thorough explorative analyses. PMID- 26828778 TI - Ab initio molecular dynamics simulations of short-range order in Zr50Cu45Al5 and Cu50Zr45Al5 metallic glasses. AB - Comparative analysis between Zr-rich Zr50Cu45Al5 and Cu-rich Cu50Zr45Al5 metallic glasses (MGs) is extensively performed to locate the key structural motifs accounting for their difference of glass forming ability. Here we adopt ab initio molecular dynamics simulations to investigate the local atomic structures of Zr50Cu45Al5 and Cu50Zr45Al5 MGs. A high content of icosahedral-related (full and distorted) orders was found in both samples, while in the Zr-rich MG full icosahedrons ?0, 0, 12, 0? is dominant, and in the Cu-rich one the distorted icosahedral orders, especially ?0, 2, 8, 2? and ?0, 2, 8, 1?, are prominent. And the ?0, 2, 8, 2? polyhedra in Cu50Zr45Al5 MG mainly originate from Al-centered clusters, while the ?0, 0, 12, 0? in Zr50Cu45Al5 derives from both Cu-centered clusters and Al-centered clusters. These difference may be ascribed to the atomic size difference and chemical property between Cu and Zr atoms. The relatively large size of Zr and large negative heat of mixing between Zr and Al atoms, enhancing the packing density and stability of metallic glass system, may be responsible for the higher glass forming ability of Zr50Cu45Al5. PMID- 26828774 TI - Carnitine transport and fatty acid oxidation. AB - Carnitine is essential for the transfer of long-chain fatty acids across the inner mitochondrial membrane for subsequent beta-oxidation. It can be synthesized by the body or assumed with the diet from meat and dairy products. Defects in carnitine biosynthesis do not routinely result in low plasma carnitine levels. Carnitine is accumulated by the cells and retained by kidneys using OCTN2, a high affinity organic cation transporter specific for carnitine. Defects in the OCTN2 carnitine transporter results in autosomal recessive primary carnitine deficiency characterized by decreased intracellular carnitine accumulation, increased losses of carnitine in the urine, and low serum carnitine levels. Patients can present early in life with hypoketotic hypoglycemia and hepatic encephalopathy, or later in life with skeletal and cardiac myopathy or sudden death from cardiac arrhythmia, usually triggered by fasting or catabolic state. This disease responds to oral carnitine that, in pharmacological doses, enters cells using the amino acid transporter B(0,+). Primary carnitine deficiency can be suspected from the clinical presentation or identified by low levels of free carnitine (C0) in the newborn screening. Some adult patients have been diagnosed following the birth of an unaffected child with very low carnitine levels in the newborn screening. The diagnosis is confirmed by measuring low carnitine uptake in the patients' fibroblasts or by DNA sequencing of the SLC22A5 gene encoding the OCTN2 carnitine transporter. Some mutations are specific for certain ethnic backgrounds, but the majority are private and identified only in individual families. Although the genotype usually does not correlate with metabolic or cardiac involvement in primary carnitine deficiency, patients presenting as adults tend to have at least one missense mutation retaining residual activity. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. PMID- 26828779 TI - Proposed Framework for Presenting Injury Data Using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) Diagnosis Codes. AB - Frameworks based on the International Classification of Diseases (ICD) provide injury researchers and epidemiologists with standard approaches for presenting and analyzing injury-related mortality and morbidity data. Injury diagnosis frameworks, such as the Barell Matrix for the ICD Ninth Revision, Clinical Modification (ICD-9-CM) and the Injury Mortality Diagnosis Matrix for the ICD Tenth Revision (ICD-10), categorize ICD codes into major body region (e.g., head, chest, abdomen, or extremity) by nature-of-injury (e.g., fracture, laceration, organ injury, or vascular injury) categories. In the United States, morbidity coding transitioned from ICD-9- CM to ICD-10-CM on October 1, 2015. In preparation for the use of ICD-10-CMcoded morbidity data for injury surveillance and data analysis, the National Center for Health Statistics and the National Center for Injury Prevention and Control propose an ICD-10-CM Injury Diagnosis Matrix to provide a standard approach for categorizing injuries by body region and nature of injury. This report provides a brief description of the differences between ICD-9-CM and ICD-10-CM injury diagnosis codes, introduces the proposed framework and the methods used to create it, and provides a list of additional considerations for review and comment by researchers and subjectmatter experts in injury data and surveillance. PMID- 26828780 TI - Population performance of SEM parceling strategies under measurement and structural model misspecification. AB - Previous research has suggested that the use of item parcels in structural equation modeling can lead to biased structural coefficient estimates and low power to detect model misspecification. The present article describes the population performance of items, parcels, and scales under a range of model misspecifications, examining structural path coefficient accuracy, power, and population fit indices. Results revealed that, under measurement model misspecification, any parceling scheme typically results in more accurate structural parameters, but less power to detect the misspecification. When the structural model is misspecified, parcels do not affect parameter accuracy, but they do substantially elevate power to detect the misspecification. Under particular, known measurement model misspecifications, a parceling scheme can be chosen to produce the most accurate estimates. The root mean square error of approximation and the standardized root mean square residual are more sensitive to measurement model misspecification in parceled models than the likelihood ratio test statistic. (PsycINFO Database Record PMID- 26828781 TI - Urinary catecholamines and the relationship with blood pressure and pharmacological therapy. AB - OBJECTIVES: Our aim was to assess the importance of the sympathetic nervous system as assessed by urinary catecholamine measurement in the aetiology of essential hypertension and the importance of antihypertensive therapy in the excretion of urinary catecholamines. METHODS: Twenty-four-hour urinary catecholamine measurement was performed in 1925 patients who were referred for treatment of hypertension and grouped according to the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classification: of the 655 untreated patients, 59 were normotensive individuals (SBP < 140 and DBP < 90 mmHg), n = 219 stage 1 (SBP 140 159 or DBP 90-99 mmHg), n = 236 stage 2 (SBP 160-179 or DBP 100-109 mmHg) and n = 141 stage 3 (SBP >= 180 or DBP >= 110 mmHg). RESULTS: There was a statistically significant positive relationship between 24-h urinary norepinephrine excretion and the severity of hypertension, such that the higher the blood pressure the higher the urinary norepinephrine excretion (mean +/- standard error of mean): normotensive group, 221 +/- 13 nmol/24 h; stage 1, 254 +/- 8 nmol/24 h; stage 2, 263 +/- 7 nmol/24 h and stage 3, 296 +/- 12 nmol/24 h (P < 0.001). The above relationship remained highly significant when corrected for urinary creatinine, weight, age and sex. No differences were found with urinary epinephrine or dopamine excretion. Urinary norepinephrine excretion was increased in those patients taking single-drug therapy with either a long-acting dihydropyridine calcium antagonist or a beta-blocker. CONCLUSION: Our results demonstrate that in untreated hypertensive patients, urinary norepinephrine excretion is increased in proportion to the severity of blood pressure rise and also in patients taking a long-acting dihydropyridine calcium antagonist or a beta-blocker. Sympathetic overactivity may play a role in the aetiology and maintenance of essential hypertension. PMID- 26828782 TI - Accelerometer-determined physical activity and all-cause mortality in a national prospective cohort study of hypertensive adults. AB - OBJECTIVE: Research in the general population suggests an inverse association between physical activity and all-cause mortality. Less research on this topic has been conducted among hypertensive adults, but the limited studies also suggest an inverse association between physical activity and all-cause mortality among hypertensive adults. At this point, sex-specific differences are not well understood, and all of the physical activity-mortality studies among hypertensive adults have employed a self-report measure of physical activity. Therefore, the purpose of this study was to examine the sex-specific association between objectively measured physical activity and all-cause mortality among a national sample of hypertensive adults. METHODS: Data from the 2003 to 2006 National Health and Nutrition Examination Survey, with follow-up through 2011, were employed. Hypertension status was defined using measured blood pressure and use of blood pressure-lowering medication. Physical activity was assessed via accelerometry. RESULTS: After adjustments, for every 60-min increase in physical activity, hypertensive adults had a 19% (hazard rate = 0.81; 95% confidence interval: 0.72-0.91) reduced risk of all-cause mortality. There was also evidence of a dose-response relationship. Compared with those in the lowest tertile, those in the middle and upper tertiles had a 31 and 42% reduced all-cause mortality risk, respectively. There was no evidence of a sex-specific interaction effect. CONCLUSION: Among hypertensive adults, objectively measured physical activity is associated with all-cause mortality risk in a dose-response manner. PMID- 26828783 TI - AT1-receptor blockade, but not renin inhibition, reduces aneurysm growth and cardiac failure in fibulin-4 mice. AB - AIMS: Increasing evidence supports a role for the angiotensin II-AT1-receptor axis in aneurysm development. Here, we studied whether counteracting this axis via stimulation of AT2 receptors is beneficial. Such stimulation occurs naturally during AT1-receptor blockade with losartan, but not during renin inhibition with aliskiren. METHODS AND RESULTS: Aneurysmal homozygous fibulin-4 mice, displaying a four-fold reduced fibulin-4 expression, were treated with placebo, losartan, aliskiren, or the beta-blocker propranolol from day 35 to 100. Their phenotype includes cystic media degeneration, aortic regurgitation, left ventricular dilation, reduced ejection fraction, and fractional shortening. Although losartan and aliskiren reduced hemodynamic stress and increased renin similarly, only losartan increased survival. Propranolol had no effect. No drug rescued elastic fiber fragmentation in established aneurysms, although losartan did reduce aneurysm size. Losartan also increased ejection fraction, decreased LV diameter, and reduced cardiac pSmad2 signaling. None of these effects were seen with aliskiren or propranolol. Longitudinal micro-CT measurements, a novel method in which each mouse serves as its own control, revealed that losartan reduced LV growth more than aneurysm growth, presumably because the heart profits both from the local (cardiac) effects of losartan and its effects on aortic root remodeling. CONCLUSION: Losartan, but not aliskiren or propranolol, improved survival in fibulin-4 mice. This most likely relates to its capacity to improve structure and function of both aorta and heart. The absence of this effect during aliskiren treatment, despite a similar degree of blood pressure reduction and renin-angiotensin system blockade, suggests that it might be because of AT2 receptor stimulation. PMID- 26828784 TI - Beta-cell function is associated with carotid intima-media thickness independently of insulin resistance in healthy individuals. AB - OBJECTIVE: It is a common belief that early atherosclerosis in prediabetes is causally linked to endothelial insulin resistance. Another condition, a low insulin secretion, may be associated with insufficient insulin action on the vascular wall and consequently favor atherosclerosis. Our aim was to test this hypothesis in people without diabetes, taking into account the gold-standard measurement of insulin sensitivity, a major confounder in the relationship between insulin secretion and atherosclerosis. METHODS: We studied the European Relationship between Insulin Sensitivity and Cardiovascular Risk cohort of 451 men and 593 women (44 +/- 8 years, mean +/- SD) who were free of diabetes, hypertension, dyslipidemia, and other known chronic or acute conditions. All underwent an oral glucose tolerance test, a euglycemic-hyperinsulinemic clamp (M/I measured insulin sensitivity), and B-mode carotid ultrasound. RESULTS: Intima-media thickness (IMT) in the common carotid artery was negatively associated with insulin secretion indexes, with Spearman partial correlation coefficients: -0.09, -0.08, -0.06 for respectively, the disposition index, the early insulin response and the beta cell glucose sensitivity, after adjusting for established factors, including clamp-measured insulin sensitivity (all P < 0.05). For quartiles 1 (lowest) to 4 of the disposition index, the covariate-adjusted geometric means of IMT (mm) were 0.605 (95% confidence interval: 0.596-0.614), 0.596 (0.587-0.605), 0.597 (0.587-0.606), and 0.586 (0.577-0.596) (Ptrend = 0.004). Similar results were found for the two other surrogate measures of insulin secretion. No interaction with sex was observed. CONCLUSION: Insulin secretion was associated with early carotid atherosclerosis in nondiabetic individuals, independently of other risk factors, including insulin sensitivity measured by the gold-standard method. PMID- 26828785 TI - Waist circumference modifies the association between serum 25(OH)D and systolic blood pressure: results from NHANES 2001-2006. AB - OBJECTIVE: Results on the association between vitamin D and blood pressure are conflicting and little is known about how their relationship may be affected by obesity. Thus, we explored whether waist circumference modified the association between serum 25-hydroxyvitamin D (25(OH)D) and blood pressure in participants of the U.S. National Health and Nutrition Examination Surveys 2001-2006. METHODS: We included 10 331 nonpregnant participants aged 20 years or older. The association of serum 25(OH)D with systolic and diastolic blood pressure, in the total sample and stratified by waist circumference category (abdominal overweight: 80 to <88 cm in females / 94 to <102 cm in males; abdominal obesity: >=88 cm in females/ >=102 cm in males), was examined using multiple linear regression. Effect modification by waist circumference was assessed through a cross-product interaction term between 25(OH)D category and waist circumference category. RESULTS: Waist circumference significantly modified the inverse association between 25(OH)D and systolic blood pressure (SBP) (P value for interaction: 0.09). A stronger association of 25(OH)D levels below 15 ng/ml (reference: >=30 ng/ml) with SBP was found in abdominally obese (beta = 3.5 mmHg) than in abdominally overweight (beta = 2.0 mmHg) and normal waist participants (beta = 1.2 mmHg), but this interaction was only significant in participants without antihypertensive treatment. No significant effect modification was found for diastolic blood pressure. CONCLUSION: Results from this large, cross-sectional sample suggest that the association between 25(OH)D and SBP is stronger in individuals with abdominal obesity than in those with a normal waist or with abdominal overweight. PMID- 26828786 TI - Doppler indexes of left ventricular systolic and diastolic function in relation to the arterial stiffness in a general population. AB - BACKGROUND: Late-systolic loading of the left ventricular (LV) is determined by arterial wave reflections and central vascular stiffening. We, therefore, investigated the relationship between various Doppler indexes reflecting LV systolic and diastolic function and arterial stiffness in the framework of a large population study of randomly recruited study participants. METHODS: In 1233 study participants (51.7% women; mean age, 48 years; 41.5% hypertensive), using conventional and tissue Doppler imaging, we measured: the transmitral early (E) and late (A) diastolic velocities; tissue Doppler imaging systolic and early (e') and late diastolic mitral annular velocities; and end-systolic longitudinal and radial strain. Using applanation tonometry, we assessed central pulse pressure (cPP), augmentation pressure and carotid-femoral pulse wave velocity. RESULTS: After full adjustment, transmitral E and A peaks increased with augmentation pressure and cPP (P less than 0.0001) and e' was positively associated with cPP (P = 0.013). The E/e' ratio increased significantly with augmentation pressure (P less than 0.0001), cPP (P less than 0.0001) and pulse wave velocity (P = 0.048). Although accounting for covariables, all arterial indexes were on average significantly higher in the diastolic dysfunction group with elevated filling pressure (n = 171) when compared to participants with normal diastolic function (n = 961; P <= 0.0004) or with impaired relaxation (n = 101; P <= 0.008). Longitudinal strain decreased independently with mean arterial pressure (P = 0.03). The correlation between radial strain and the arterial indexes shifted from positive at middle age (50-60 years) to negative at older (P less than 0.0001 for interaction). CONCLUSION: Our study underscored the importance of arterial characteristics as a mediator of LV systolic and diastolic dysfunction. We demonstrated an age-dependent relationship between radial strain and indexes of arterial stiffness. PMID- 26828787 TI - Plasma B-type natriuretic peptide concentration is independently associated with kidney function decline in Japanese patients with chronic kidney disease. AB - BACKGROUND AND OBJECTIVE: The relationship between B-type natriuretic peptide (BNP) concentration and renal outcomes in patients with chronic kidney disease (CKD) remains unclear; therefore, it has not been determined whether BNP is related to renal outcomes, independent of cardiac parameters. This study was designed to clarify whether BNP concentration is associated with renal outcomes in CKD patients, independent of cardiac functional and structural alterations. METHODS: This prospective observational study included 372 consecutive patients with CKD. The renal endpoint was the composite of doubling of serum creatinine concentration and end-stage renal disease requiring dialysis. BNP concentrations were divided into quartiles. A Cox proportional hazards model was utilized to determine the risk factors for poor renal outcomes. RESULTS: During a median follow-up of 23.1 months, the renal endpoint was observed in 124 patients, including 14, 18, 37 and 55 patients in the first through fourth BNP quartiles, respectively. After adjustment for covariates, including cardiac parameters such as left atrial diameter, left ventricular mass index, left ventricular ejection fraction, and left ventricular hypertrophy, the hazard ratios (HRs) for renal outcomes became progressively higher for the second [HR, 1.50; 95% confidence interval (CI), 0.70-3.30), third (HR, 2.29; 95% CI, 1.11-4.91), and fourth (HR, 4.29; 95% CI, 2.05-9.39) BNP quartiles when compared with the lowest BNP quartile. CONCLUSION: Higher BNP levels were associated with adverse renal outcomes, independent of cardiac structure and function, suggesting that BNP may be a useful biomarker for exploring factors associated with kidney disease progression. PMID- 26828788 TI - Bevacizumab beyond disease progression after first-line treatment with bevacizumab plus chemotherapy in advanced nonsquamous non-small cell lung cancer (West Japan Oncology Group 5910L): An open-label, randomized, phase 2 trial. AB - BACKGROUND: Bevacizumab combined with platinum-based chemotherapy has been established as a standard treatment option in the first-line setting for advanced nonsquamous non-small cell lung cancer (NSCLC). However, there has been no evidence to support the use of bevacizumab beyond disease progression in such patients. METHODS: West Japan Oncology Group 5910L was designed as a multicenter, open-label, randomized, phase 2 trial of docetaxel versus docetaxel plus bevacizumab every 3 weeks for patients with recurrent or metastatic nonsquamous NSCLC whose disease had progressed after first-line treatment with bevacizumab plus a platinum-based doublet. The primary endpoint was progression-free survival (PFS). RESULTS: One hundred patients were randomly assigned to receive docetaxel (n = 50) or docetaxel plus bevacizumab (n = 50), and this yielded median PFS times of 3.4 and 4.4 months, respectively, with a hazard ratio (HR) of 0.71 and a stratified log-rank P value of .058, which met the predefined criterion for statistical significance (P < .2). The median overall survival also tended to be longer in the docetaxel plus bevacizumab group (13.1 months; 95% confidence interval [CI], 10.6-21.4 months) versus the docetaxel group (11.0 months; 95% CI, 7.6-16.1 months) with an HR of 0.74 (95% CI, 0.46-1.19; stratified log-rank P = .11). No unexpected or severe adverse events were recorded. CONCLUSIONS: Further evaluation of bevacizumab beyond disease progression is warranted for patients with advanced NSCLC whose disease has progressed after treatment with bevacizumab plus a platinum-based doublet. PMID- 26828789 TI - Exploring biomechanical methods to study the human vaginal wall. AB - AIMS: To critically review studies of the biomechanical properties of connective tissue in the normal and prolapsed human vaginal wall and to identify criteria that are suitable for in vivo measurements which could improve patient management. METHODS: This review covers past and current ex vivo and in vivo instrumentation and analytical methods related to the elastic and viscoelastic properties of vaginal wall connective tissues. RESULTS: Classical methods, including digital evaluation of the vagina, histological and biomechanical studies of fresh and frozen-thawed extracts, and biomechanical cadaveric tissue studies have important limitations and have yielded inconsistent results. Newer biomechanical methods may resolve these inconsistencies. One of the more promising is transient, vacuum-induced tissue expansion and relaxation, via cutometer-like devices. The technique permits noninvasive observation, applicable to longitudinal studies of patients. In vivo and ex vivo biomechanical methods may better match vaginal wall tissue properties to help with the design of surgical mesh materials, thus improving surgical support and healing. CONCLUSION: Methods have been identified to characterize the in vivo biomechanical behavior of the prolapsing vagina which may serve to advance the care of affected women. Neurourol. Urodynam. 36:499-506, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26828790 TI - Maturation of Mechanical Impedance of the Skin-Covered Skull: Implications for Soft Band Bone-Anchored Hearing Systems Fitted in Infants and Young Children. AB - OBJECTIVES: Little is known about the maturational changes in the mechanical properties of the skull and how they might contribute to infant-adult differences in bone conduction hearing sensitivity. The objective of this study was to investigate the mechanical impedance of the skin-covered skull for different skull positions and contact forces for groups of infants, young children, and adults. These findings provide a better understanding of how changes in mechanical impedance might contribute to developmental changes in bone conduction hearing, and might provide insight into how fitting and output verification protocols for bone-anchored hearing systems (BAHS) could be adapted for infants and young children. DESIGN: Seventy-seven individuals participated in the study, including 63 infants and children (ages 1 month to 7 years) and 11 adults. Mechanical impedance magnitude for the forehead and temporal bone was collected for contact forces of 2, 4, and 5.4 N using an impedance head, a BAHS transducer, and a specially designed holding device. Mechanical impedance magnitude was determined across frequency using a stepped sine sweep from 100 to 10,000 Hz, and divided into low- and high-frequency sets for analysis. RESULTS: Mechanical impedance magnitude was lowest for the youngest infants and increased throughout maturation in the low frequencies. For high frequencies, the youngest infants had the highest impedance, but only for a temporal bone placement. Impedance increased with increasing contact force for low frequencies for each age group and for both skull positions. The effect of placement was significant for high frequencies for each contact force and for each age group, except for the youngest infants. CONCLUSIONS: Our findings show that mechanical impedance properties change systematically up to 7 years old. The significant age-related differences in mechanical impedance suggest that infant-adult differences in bone conduction thresholds may be related, at least in part, to properties of the immature skull and overlying skin and tissues. These results have important implications for fitting the soft band BAHS on infants and young children. For example, verification of output force form a BAHS on a coupler designed with adult values may not be appropriate for infants. This may also hold true for transducer calibration when assessing bone conduction hearing thresholds in infants for different skull locations. The results have two additional clinical implications for fitting soft band BAHSs. First, parents should be counseled to maintain sufficient and consistent tightness so that the output from the BAHS does not change as the child moves around during everyday activities. Second, placement of a BAHS on the forehead versus the temporal bone results in changes in mechanical impedance which may contribute to a decrease in signal level at the cochlea as it has been previously demonstrated that bone conduction thresholds are poorer at the forehead compared with a temporal placement. PMID- 26828791 TI - Polymorphisms in the AKT1 and AKT2 genes and oesophageal squamous cell carcinoma risk in an Eastern Chinese population. AB - Ethnic Han Chinese are at high risk of developing oesophageal squamous cell carcinoma (ESCC). Aberrant activation of the AKT signalling pathway is involved in many cancers, including ESCC. Some single nucleotide polymorphisms (SNPs) in genes involved in this pathway may contribute to ESCC susceptibility. We selected five potentially functional SNPs in AKT1 (rs2494750, rs2494752 and rs10138277) and AKT2 (rs7254617 and rs2304186) genes and investigated their associations with ESCC risk in 1117 ESCC cases and 1096 controls in an Eastern Chinese population. None of individual SNPs exhibited an association with ESCC risk. However, the combined analysis of three AKT1 SNPs suggested that individuals carrying one of AKT1 variant genotypes had a decreased ESCC risk [adjusted odds ratio (OR) = 0.60, 95% CI = 0.42-0.87]. Further stratified analysis found that AKT1 rs2294750 SNP was associated with significantly decreased ESCC risk among women (adjusted OR = 0.63, 95% CI = 0.43-0.94) and non-drinkers (OR = 0.79, 95% CI = 0.64-0.99). Similar protective effects on women (adjusted OR = 0.56, 95% CI = 0.37-0.83) and non-drinker (adjusted OR = 0.75, 95% CI = 0.60-0.94) were also observed for the combined genotypes of AKT1 SNPs. Consistently, logistic regression analysis indicated significant gene-gene interactions among three AKT1 SNPs (P < 0.015). A three-AKT1 SNP haplotype (C-A-C) showed a significant association with a decreased ESCC risk (adjusted OR = 0.70, 95% CI = 0.52-0.94). Multifactor dimensionality reduction analysis confirmed a high-order gene-environment interaction in ESCC risk. Overall, we found that three AKT1 SNPs might confer protection against ESCC risk; nevertheless, these effects may be dependent on other risk factors. Our results provided evidence of important gene-environment interplay in ESCC carcinogenesis. PMID- 26828792 TI - Characterization and Inducing Melanoma Cell Apoptosis Activity of Mannosylerythritol Lipids-A Produced from Pseudozyma aphidis. AB - Mannosylerythritol lipids (MELs) are natural glycolipid biosurfactants which have potential applications in the fields of food, cosmetic and medicine. In this study, MELs were produced from vegetable oil by Pseudozyma aphidis. Their structural data through LC/MS, GC/MS and NMR analysis revealed that MEL-A with two acetyls was the major compound and the identified homologs of MEL-A contained a length of C8 to C14 fatty acid chains. This glycolipid exhibited a surface tension of 27.69 mN/m at a critical micelle concentration (CMC), self-assembling into particles in the water solution. It was observed to induce cell growth inhibition and apoptosis of B16 melanoma cells in a dose-dependent manner, as well as cause cell cycle arrest at the S phase. Further quantitative RT-PCR analysis and western blotting revealed an increasing tendency of both mRNA and protein expressions of Caspase-12, CHOP, GRP78 and Caspase-3, and a down regulation of protein Bcl-2. Combined with the up regulation of signaling IRE1 and ATF6, it can be speculated that MEL-A-induced B16 melanoma cell apoptosis was associated with the endoplasmic reticulum stress (ERS). PMID- 26828793 TI - Iterative Usage of Fixed and Random Effect Models for Powerful and Efficient Genome-Wide Association Studies. AB - False positives in a Genome-Wide Association Study (GWAS) can be effectively controlled by a fixed effect and random effect Mixed Linear Model (MLM) that incorporates population structure and kinship among individuals to adjust association tests on markers; however, the adjustment also compromises true positives. The modified MLM method, Multiple Loci Linear Mixed Model (MLMM), incorporates multiple markers simultaneously as covariates in a stepwise MLM to partially remove the confounding between testing markers and kinship. To completely eliminate the confounding, we divided MLMM into two parts: Fixed Effect Model (FEM) and a Random Effect Model (REM) and use them iteratively. FEM contains testing markers, one at a time, and multiple associated markers as covariates to control false positives. To avoid model over-fitting problem in FEM, the associated markers are estimated in REM by using them to define kinship. The P values of testing markers and the associated markers are unified at each iteration. We named the new method as Fixed and random model Circulating Probability Unification (FarmCPU). Both real and simulated data analyses demonstrated that FarmCPU improves statistical power compared to current methods. Additional benefits include an efficient computing time that is linear to both number of individuals and number of markers. Now, a dataset with half million individuals and half million markers can be analyzed within three days. PMID- 26828795 TI - Vermicomposting as an advanced biological treatment for industrial waste from the leather industry. AB - The leather industry (tanneries) generates high amounts of toxic wastes, including solid and liquid effluents that are rich in organic matter and mineral content. Vermicomposting was studied as an alternative method of treating the wastes from tanneries. Vermicompost was produced from the following tannery residues: tanned chips of wet-blue leather, sludge from a liquid residue treatment station, and a mixture of both. Five hundred earthworms (Eisenia fetida) were added to each barrel. During the following 135 days the following parameters were evaluated: pH, total organic carbon (TOC), organic matter (OM), cation exchange capacity (CEC), C:N ratio, and chromium content as Cr (III) and Cr (VI). The results for pH, TOC and OM contents showed decreases in their values during the composting process, whereas values for CEC and total nitrogen rose, indicating that the vermicompost reached maturity. For chromium, at 135 days, all values of Cr (VI) were below the detectable level. Therefore, the Cr (VI) content had probably been biologically transformed into Cr (III), confirming the use of this technique as an advanced biological treatment. The study reinforces the idea that vermicomposting could be introduced as an effective technology for the treatment of industrial tannery waste and the production of agricultural inputs. PMID- 26828794 TI - Crystal Structure of a Ube2S-Ubiquitin Conjugate. AB - Protein ubiquitination occurs through the sequential formation and reorganization of specific protein-protein interfaces. Ubiquitin-conjugating (E2) enzymes, such as Ube2S, catalyze the formation of an isopeptide linkage between the C-terminus of a "donor" ubiquitin and a primary amino group of an "acceptor" ubiquitin molecule. This reaction involves an intermediate, in which the C-terminus of the donor ubiquitin is thioester-bound to the active site cysteine of the E2 and a functionally important interface is formed between the two proteins. A docked model of a Ube2S-donor ubiquitin complex was generated previously, based on chemical shift mapping by NMR, and predicted contacts were validated in functional studies. We now present the crystal structure of a covalent Ube2S ubiquitin complex. The structure contains an interface between Ube2S and ubiquitin in trans that resembles the earlier model in general terms, but differs in detail. The crystallographic interface is more hydrophobic than the earlier model and is stable in molecular dynamics (MD) simulations. Remarkably, the docked Ube2S-donor complex converges readily to the configuration seen in the crystal structure in 3 out of 8 MD trajectories. Since the crystallographic interface is fully consistent with mutational effects, this indicates that the structure provides an energetically favorable representation of the functionally critical Ube2S-donor interface. PMID- 26828796 TI - Oxidation of Phe454 in the Gating Segment Inactivates Trametes multicolor Pyranose Oxidase during Substrate Turnover. AB - The flavin-dependent enzyme pyranose oxidase catalyses the oxidation of several pyranose sugars at position C-2. In a second reaction step, oxygen is reduced to hydrogen peroxide. POx is of interest for biocatalytic carbohydrate oxidations, yet it was found that the enzyme is rapidly inactivated under turnover conditions. We studied pyranose oxidase from Trametes multicolor (TmPOx) inactivated either during glucose oxidation or by exogenous hydrogen peroxide using mass spectrometry. MALDI-MS experiments of proteolytic fragments of inactivated TmPOx showed several peptides with a mass increase of 16 or 32 Da indicating oxidation of certain amino acids. Most of these fragments contain at least one methionine residue, which most likely is oxidised by hydrogen peroxide. One peptide fragment that did not contain any amino acid residue that is likely to be oxidised by hydrogen peroxide (DAFSYGAVQQSIDSR) was studied in detail by LC ESI-MS/MS, which showed a +16 Da mass increase for Phe454. We propose that oxidation of Phe454, which is located at the flexible active-site loop of TmPOx, is the first and main step in the inactivation of TmPOx by hydrogen peroxide. Oxidation of methionine residues might then further contribute to the complete inactivation of the enzyme. PMID- 26828797 TI - Mobile Phone Use Behaviors and Postures on Public Transportation Systems. AB - Mobile phones are common in our daily life, but the users' preferences for postures or screen operating styles have not been studied. This was a cross sectional and observational study. We randomly sampled passengers who used mobile phones on the Mass Rapid Transit (MRT) system in metropolitan Taipei. A checklist was used to observe their body postures and screen operating styles while sitting or standing. As a result, 1,230 subjects from 400 trips were observed. Overall, of all the passengers who were sitting, 41% of them were using mobile phones. The majority of the tasks involved browsing (84%) with their phones in a portrait orientation (93%). Different-hand holding/operating was the most commonly used operating style while sitting (46%) and same-hand holding/operating was the most common while standing (46%). The distribution of screen operating styles was significantly different for those sitting than for those standing and for different genders and age groups. The most frequently observed postures while sitting were having one's trunk against a backrest, feet on the floor and with or without an arm supported (58%). As for the users who were standing, the both- and different-hands groups had a high proportion of arms unsupported, feet on the floor and either their trunk supported or not. In contrast, the same-hand group tended to have their trunk unsupported, were holding a pole or handstrap and had both feet on floor. Further studies are warranted to characterize the ergonomic exposure of these commonly used postures and operating styles, and our results will help guide the selection of experimental conditions for laboratory settings. PMID- 26828798 TI - The Impact of Simulated Weightlessness on Endothelium-Dependent Angiogenesis and the Role of Caveolae/Caveolin-1. AB - BACKGROUND/AIMS: The potential role of caveolin-1 in modulating angiogenesis in microgravity environment is unexplored. METHODS: Using simulated microgravity by clinostat, we measured the expressions and interactions of caveolin-1 and eNOS in human umbilical vein endothelial cells. RESULTS: We found that decreased caveolin 1 expression is associated with increased expression and phosphorylation levels of eNOS in endothelial cells stimulated by microgravity, which causes a dissociation of eNOS from caveolin-1 complexes. As a result, microgravity induces cell migration and tube formation in endothelial cell in vitro that depends on the regulations of caveolin-1. CONCLUSION: Our study provides insight for the important endothelial functions in altered gravitational environments. PMID- 26828799 TI - A Conceptual Framework for Allocation of Federally Stockpiled Ventilators During Large-Scale Public Health Emergencies. AB - Some types of public health emergencies could result in large numbers of patients with respiratory failure who need mechanical ventilation. Federal public health planning has included needs assessment and stockpiling of ventilators. However, additional federal guidance is needed to assist states in further allocating federally supplied ventilators to individual hospitals to ensure that ventilators are shipped to facilities where they can best be used during an emergency. A major consideration in planning is a hospital's ability to absorb additional ventilators, based on available space and staff expertise. A simple pro rata plan that does not take these factors into account might result in suboptimal use or unused scarce resources. This article proposes a conceptual framework that identifies the steps in planning and an important gap in federal guidance regarding the distribution of stockpiled mechanical ventilators during an emergency. PMID- 26828800 TI - Translocation of flexible polymersomes across pores at the nanoscale. AB - Hierarchical biological systems such as tissues and organs are often characterised by highly crowded and packed environments with nanoscopic interconnections between them. Engineering nanovectors that can penetrate and diffuse across these is critical to ensure enhanced delivery and targeting. Here we demonstrate that flexible polymeric vesicles, known as polymersomes, enable the translocation of large macromolecules across both synthetic and biological porous systems. We compare the translocation across narrow pores of different polymersome formulations. We demonstrate that effective translocation depends on the right combination of mechanical properties and surface lubrication. We prove that with the effect of external gradients (e.g. osmotic pressure, capillarity, hydration, etc.) polymersomes can translocate across pores with diameters one order of magnitude smaller without breaking. We demonstrate that these properties are essential to develop effective tissue penetration and show polymersome mediated transdermal delivery of large macromolecules such as dextran and antibodies using human ex vivo skin. PMID- 26828801 TI - Paraspinous Lidocaine Injection for Chronic Nonspecific Low Back Pain: A Randomized Controlled Clinical Trial. AB - In this large, sham-controlled, randomized trial, we examined the efficacy of the combination of standard treatment and paraspinous lidocaine injection compared with standard therapy alone in subjects with chronic low back pain. There is little research-based evidence for the routine clinical use of paraspinous lidocaine injection for low back pain. A total of 378 subjects with nonspecific chronic low back pain were randomized to 3 groups: paraspinous lidocaine injection, analgesics, and exercises (group 1, LID-INJ); sham paraspinous lidocaine injection, analgesics, and exercises (group 2, SH-INJ); and analgesics and exercises (group 3, STD-TTR). A blinded rater assessed the study outcomes at 3 time points: baseline, after treatment, and after 3 months of follow-up. There were increased frequency of pain responses and better low back functional scores in the LID-INJ group compared with the SH-INJ and STD-TTR groups. These effects remained at the 3-month follow-up but differed between all 3 groups. There were significant changes in pain threshold immediately after treatment, supporting the effects of this intervention in reducing central sensitization. Paraspinous lidocaine injection therapy is not associated with a higher risk of adverse effects compared with conventional treatment and sham injection. Its effects on hyperalgesia might correlate with changes in central sensitization. CLINICAL TRIAL REGISTRATION: NCT02387567. PERSPECTIVE: There are few data to support paraspinous lidocaine injection use in patients with nonspecific chronic low back pain. Our results show that this therapy when combined with standard therapy significantly increases the number of responders versus standard treatment alone. Its effects on hyperalgesia might correlate with a change in central sensitization. PMID- 26828802 TI - Trends in Opioid Dosing Among Washington State Medicaid Patients Before and After Opioid Dosing Guideline Implementation. AB - By 2007, opioid-related mortality in Washington state (WA) was 50% higher than the national average, with Medicaid patients showing nearly 6 times the mortality of commercially-insured patients. In 2007, the WA Interagency Guideline on Opioid Dosing for Chronic Non-cancer Pain was released, which recommended caution in prescribing >120 mg morphine-equivalent dose per day for patients not showing clinically meaningful improvement in pain and function. We report on opioid dosing in the WA Medicaid fee-for-service population for 273,200 adults with a paid claim for an opioid prescription between April 1, 2006 and December 31, 2010. Linear regression was used to test for trends in dosing over that time period, with quarter-year as the independent variable and median daily dose as the dependent variable. Prescription opioid use among WA Medicaid adults peaked in 2009, as evidenced by the unique number of opioid users (105,232), the total number of prescriptions (556,712), and the total person-years of prescription opioid use (29,442). Median opioid dose was unchanged from 2006 to 2010 at 37.5 mg morphine-equivalent dose, but doses at the 75th, 90th, 95th, and 99th percentiles declined significantly (P < .001). These results suggest that opioid treatment guidelines with dosing guidance may be able to reduce high-dose opioid use without affecting the median dose used. PERSPECTIVE: Some fear that opioid dosing guidelines might restrict access to opioid therapy for patients who could benefit. However, there is evidence that high-dose opioid therapy entails significant risks without demonstrated benefit. These findings indicate that high dose opioid therapy can be reduced without altering median opioid dose in a Medicaid population. PMID- 26828803 TI - AUI&GIV: Recommendation with Asymmetric User Influence and Global Importance Value. AB - The user-based collaborative filtering (CF) algorithm is one of the most popular approaches for making recommendation. Despite its success, the traditional user based CF algorithm suffers one serious problem that it only measures the influence between two users based on their symmetric similarities calculated by their consumption histories. It means that, for a pair of users, the influences on each other are the same, which however may not be true. Intuitively, an expert may have an impact on a novice user but a novice user may not affect an expert at all. Besides, each user may possess a global importance factor that affects his/her influence to the remaining users. To this end, in this paper, we propose an asymmetric user influence model to measure the directed influence between two users and adopt the PageRank algorithm to calculate the global importance value of each user. And then the directed influence values and the global importance values are integrated to deduce the final influence values between two users. Finally, we use the final influence values to improve the performance of the traditional user-based CF algorithm. Extensive experiments have been conducted, the results of which have confirmed that both the asymmetric user influence model and global importance value play key roles in improving recommendation accuracy, and hence the proposed method significantly outperforms the existing recommendation algorithms, in particular the user-based CF algorithm on the datasets of high rating density. PMID- 26828805 TI - The role of allophony and frequency in the acquisition of the Hebrew rhotic. AB - This article investigates the role of allophonic variation in phoneme acquisition and the clinical implications of this role. Specifically, we investigate the Hebrew rhotic /?/. We analyse its production by Hebrew-acquiring children in various corpora, comparing the deletion, substitution and production in word initial onset, intervocalic and word-final coda positions. The results are compared to the frequency of rhotics in a child-directed speech (CDS) corpus and in a Hebrew lexicon analysis. The study shows rhotics are acquired first in word final codas, then in intervocalic position and finally as word-initial onsets. The order of acquisition, demonstrated by the deletion and substitution patterns, and the actual production of Hebrew rhotics correlate with the degree of allophonic variation. It does not, however, correlate with the frequency patterns observed in CDS and the Hebrew lexicon. Further study of allophonic variation and acquisition should include additional phonemes in Hebrew, as well as other languages. PMID- 26828804 TI - No relationship between lipoprotein-associated phospholipase A2, proinflammatory cytokines, and neopterin in Alzheimer's disease. AB - OBJECTIVE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a reported risk factor for dementia. However, the relationship between Alzheimer's disease (AD) and Lp-PLA2 is still debatable and, to the best of our knowledge, no study has evaluated the associations between levels of Lp-PLA2, proinflammatory cytokines, and neopterin in AD. METHODS: In total, 59 patients with AD and 38 non-demented individuals were included in the case-control study. Fasting serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), neopterin, and Lp-PLA2 were determined using ELISA. The associations between AD and each of the variables were analyzed by logistic regression. RESULTS: The median Lp-PLA2 levels in AD and controls were similar (P=0.29, not significant). Median serum neopterin and IL-6 levels were significantly higher in patients with AD than in controls (P=0.0001 and P=0.03, respectively). In regression analyses, median neopterin levels, a lower level of education, and female gender were significantly associated with AD when compared with controls (OR, 31.44, 95% CI 3.59-275.28, P=0.002; OR, 4.35, 95% CI 1.13-16.61, P=0.032; OR, 7.25, 95% CI 1.88 28.00, P=0.004, respectively). CONCLUSION: In contrast to previous evidence suggesting its role in dementia and AD, Lp-PLA2 enzyme levels were higher in the controls, and no relationship between Lp-PLA2 and either proinflammatory cytokines or neopterin was identified in AD. Elevated neopterin levels may be considered inflammatory markers of AD. PMID- 26828806 TI - A new acylated flavonol from the aerial parts of Asteriscus maritimus (L.) Less (Asteraceae). AB - Phytochemical investigation of the flowering aerial parts of Asteriscus maritimus (L.) Less (Asteraceae) led to the isolation of a new compound: patuletin 7-O-beta D-[(2"'S) 6"(3"'-hydroxy-2"'-methyl-propanoyl)] glucopyranoside, together with five known metabolites; beta-sitosterol 2, chlorogenic acid 3, P-hydroxy methylbenzoate 4, luteolin 5 and protocatechuic acid 6. The structures of the isolated compounds were determined by comprehensive analyses of its 1D and 2D NMR, HRMS and compared with previously known analogues. The ethanolic extract of the flowering aerial parts of A. maritimus was found to be safe (LD50 = 4.6 mg/kg) and possess significant antioxidant and anti-inflammatory activities and this was in accordance with its high phenolic content (107.36 +/- 0.051 mg GAE/g extract). PMID- 26828807 TI - Pancreatic alpha-Cells and Insulin-Deficient Diabetes. PMID- 26828809 TI - Pituitary Regeneration: It'll Knock Your SOX Off! PMID- 26828808 TI - A Bisphenol by Any Other Name... PMID- 26828812 TI - Air quality mapping using GIS and economic evaluation of health impact for Mumbai City, India. AB - Mumbai, a highly populated city in India, has been selected for air quality mapping and assessment of health impact using monitored air quality data. Air quality monitoring networks in Mumbai are operated by National Environment Engineering Research Institute (NEERI), Maharashtra Pollution Control Board (MPCB), and Brihanmumbai Municipal Corporation (BMC). A monitoring station represents air quality at a particular location, while we need spatial variation for air quality management. Here, air quality monitored data of NEERI and BMC were spatially interpolated using various inbuilt interpolation techniques of ArcGIS. Inverse distance weighting (IDW), Kriging (spherical and Gaussian), and spline techniques have been applied for spatial interpolation for this study. The interpolated results of air pollutants sulfur dioxide (SO2), nitrogen dioxide (NO2) and suspended particulate matter (SPM) were compared with air quality data of MPCB in the same region. Comparison of results showed good agreement for predicted values using IDW and Kriging with observed data. Subsequently, health impact assessment of a ward was carried out based on total population of the ward and air quality monitored data within the ward. Finally, health cost within a ward was estimated on the basis of exposed population. This study helps to estimate the valuation of health damage due to air pollution. IMPLICATIONS: Operating more air quality monitoring stations for measurement of air quality is highly resource intensive in terms of time and cost. The appropriate spatial interpolation techniques can be used to estimate concentration where air quality monitoring stations are not available. Further, health impact assessment for the population of the city and estimation of economic cost of health damage due to ambient air quality can help to make rational control strategies for environmental management. The total health cost for Mumbai city for the year 2012, with a population of 12.4 million, was estimated as USD8000 million. PMID- 26828813 TI - Comparison of Histopathological Effects of Thymoquinone and Local Nasal Corticosteroids in Allergic Rhinitis in a Rabbit Model. AB - BACKGROUND/AIMS: In this study, we aimed to evaluate the histopathological effects of thymoquinone treatment of the nasal mucosa in a rabbit model of allergic rhinitis, and we compared its effects with those of nasal mometasone furoate. METHODS: A total of 24 male New Zealand rabbits were used. The animals were randomly assigned to one of four groups. Group 1 received no treatment, while group 2 underwent ovalbumin (OVA) sensitization only. Group 3 was the study group; after OVA sensitization, the rabbits were treated with intranasal thymoquinone. The group 4 rabbits received mometasone furoate for 7 days after OVA sensitization. Mucosal structures were stained with hematoxylin and eosin, while toluidine blue was used to stain mast cells. Apoptosis was evaluated using a TUNEL assay. RESULTS: In the positive control groups, including the thymoquinone and intranasal mometasone furoate groups, intraepithelial and submucosal inflammation and goblet cell hypertrophy were significantly decreased compared to group 2 (p < 0.001). The cilial structure was normal, as was the chondrocyte structure in both treatment groups. CONCLUSION: This is the first study to evaluate the histopathological effects of thymoquinone in an allergic rhinitis model. Thymoquinone reduced allergic inflammation and may be valuable for treating allergic rhinitis. However, additional studies are needed. PMID- 26828814 TI - Influence of cyclopropane fatty acids on heat, high pressure, acid and oxidative resistance in Escherichia coli. AB - Heat and high pressure resistant strains of Escherichia coli are a challenge to food safety. This study investigated effects of cyclopropane fatty acids (CFAs) on stress tolerance in the heat- and pressure-resistant strain E. coli AW1.7 and the sensitive strain E. coli MG1655. The role of CFAs was explored by disruption of cfa coding for CFA synthase with an in-frame, unmarked deletion method. Both wild-type strains consumed all the unsaturated fatty acids (C16:1 and C18:1) that were mostly converted to CFAs and a low proportion to saturated fatty acid (C16:0). Moreover, E. coli AW1.7 contained a higher proportion of membrane C19:0 cyclopropane fatty acid than E. coli MG1655 (P<0.05). The Deltacfa mutant strains did not produce CFAs, and the corresponding substrates C16:1 and C18:1 accumulated in membrane lipids. The deletion of cfa did not alter resistance to H2O2 but increased the lethality of heat, high pressure and acid treatments in E. coli AW1.7, and E. coli MG1655. E. coli AW1.7 and its Deltacfa mutant were more resistant to pressure and heat but less resistant to acid stress than E. coli MG1655. Heat resistance of wild-type strains and their Deltacfa mutant was also assessed in beef patties grilled to an internal temperature of 71 degrees C. After treatment, cell counts of wild type strains were higher than those of the Deltacfa mutant strains. In conclusion, CFA synthesis in E. coli increases heat, high pressure and acid resistance, and increases heat resistance in food. This knowledge on mechanisms of stress resistance will facilitate the design of intervention methods for improved pathogen control in food production. PMID- 26828815 TI - Killer toxin from several food-derived Debaryomyces hansenii strains effective against pathogenic Candida yeasts. AB - Candida yeasts are the dominant fungi in the healthy human microbiome, but are well-known for causing disease following a variety of perturbations. Evaluation of fungal populations from the healthy human gut revealed a significant negative correlation between the foodborne yeast, Debaryomyces hansenii, and Candida species. D. hansenii is reported to produce killer toxins (mycocins) effective against other yeast species. In order to better understand this phenomenon, a collection of 42 D. hansenii isolates was obtained from 22 cheeses and evaluated for killer activity against Candida albicans and Candida tropicalis over a range of temperatures and pH values. Twenty three strains demonstrated killer activity against both C. albicans and C. tropicalis, which was pH- and temperature dependent, with no killer activity observed for any strain at pH6.5 or higher, or at >= 35 degrees C (physiological conditions in the human gastrointestinal tract). A cell-free mycocin preparation showed transient killer activity against C. albicans at 35 degrees C and a cheese sample containing a killer D. hansenii strain demonstrated sustained killer activity against both C. albicans and C. tropicalis. Together, these observations raise the possibility that D. hansenii could influence Candida populations in the gut. PMID- 26828817 TI - Growth hormone in the eye: A comparative update. AB - Comparative studies have previously established that the eye is an extrapituitary site of growth hormone (GH) production and action in fish, amphibia, birds and mammals. In this review more recent literature and original data in this field are considered. PMID- 26828816 TI - Maternal plasma levels of complement Factor H in miscarriage and in normal pregnancy: A cohort study. AB - The incidence of clinically recognizable miscarriage in general population is up to 15%. It has been shown that complement Factor H (CFH) mRNA levels were increased in endometrium of women during early pregnancy, compared to non pregnant women. We hypothesized that patients with miscarriage could have lower protein levels of CFH. The objectives of this prospective cohort is to measure plasma levels of Factor H in pregnancies up to 20 weeks, and to investigated whether there is an association between CFH and miscarriage. Plasma levels of CFH were measured in a cohort of pregnant women, ranging from 3 to 19.6 weeks who attended a gynecologic emergency unit in Brazil. Subjects had a blood sample obtained at the first consultation and were followed up to 24 weeks. After reaching outcome, subjects were divided into 4 groups: (1) miscarriage at entry the study, (2) normal pregnancy, (3) those that evolved to miscarriage, and (4) a control group of 6 non-pregnant, fertile proven women. Kruskal-Wallis test was used for statistical analysis. From 193 eligible women, 4 were excluded due technical problems and 33 were lost to follow-up. Median levels (range) of CFH were 989.2 MUg/mL (372-1644) n=64; 1042 MUg/mL (600.7-1915) n=74; 1089 MUg/mL (813.7-1250) n=12; 1004 MUg/mL (901.7-1335) n=6 in groups 1-3 and control, respectively; p=0.46-Kruskal-Wallis; post-hoc power (1-beta)=31.6%. Therefore, median plasma levels of CFH are not different between women with miscarriage or normal pregnancy up to 19.6 weeks. PMID- 26828818 TI - Stress reactivity, condition, and foraging behavior in zebra finches: effects on boldness, exploration, and sociality. AB - The arid and semi-arid zones of Australia are characterized by highly variable and unpredictable environmental conditions which affect resources for flora and fauna. Environments which are highly unpredictable in terms of both resource access and distribution are likely to select for a variety of adaptive behavioral strategies, intrinsically linked to the physiological control of behavior. How unpredictable resource distribution has affected the coevolution of behavioral strategies and physiology has rarely been quantified, particularly not in Australian birds. We used a captive population of wild-derived zebra finches to test the relationships between behavioral strategies relating to food access and physiological responses to stress and body condition. We found that individuals that were in poorer body condition and had higher peak corticosterone levels entered baited feeders earlier in the trapping sequence of birds within the colony. We also found that individuals in poorer body condition fed in smaller social groups. Our data show that the foraging decisions which individuals make represent not only a trade-off between food access and risk of exposure, but their underlying physiological response to stress. Our data also suggest fundamental links between social networks and physiological parameters, which largely remain untested. These data demonstrate the fundamental importance of physiological mechanisms in controlling adaptive behavioral strategies and the dynamic interplay between physiological control of behavior and life-history evolution. PMID- 26828819 TI - Intracerebroventricular ghrelin treatment affects lipid metabolism in liver of rainbow trout (Oncorhynchus mykiss). AB - We aimed to elucidate in rainbow trout (Oncorhynchus mykiss) the effects of central ghrelin (GHRL) treatment on the regulation of liver lipid metabolism, and the possible modulatory effect of central GHRL treatment on the simultaneous effects of raised levels of oleate. Thus, we injected intracerebroventricularly (ICV) rainbow trout GHRL in the presence or absence of oleate and evaluated in liver variables related to lipid metabolism. Oleate treatment elicited in liver of rainbow trout decreased lipogenesis and increased oxidative capacity in agreement with previous studies. Moreover, as demonstrated for the first time in fish in the present study, GHRL also acts centrally modulating lipid metabolism in liver, resulting in increased potential for lipogenesis and decreased potential for fatty acid oxidation, i.e. the converse effects to those elicited by central oleate treatment. The simultaneous treatment of GHRL and oleate confirmed these counteractive effects. Thus, the nutrient sensing mechanisms present in hypothalamus, particularly those involved in sensing of fatty acid, are involved in the control of liver energy metabolism in fish, and this control is modulated by the central action of GHRL. These results give support to the notion of hypothalamus as an integrative place for the regulation of peripheral energy metabolism in fish. PMID- 26828820 TI - Validation of an enzyme-immunoassay for the non-invasive monitoring of faecal testosterone metabolites in male cheetahs (Acinonyx jubatus). AB - In mammals, the sex hormone testosterone is the major endocrine variable to objectify testicular activity and thus reproductive function in males. Testosterone is involved in the development and function of male reproductive physiology and sex-related behaviour. The development of a reliable androgen enzyme-immunoassay (EIA) to monitor faecal testosterone metabolites (fTM) is a powerful tool to non-invasively assess the gonadal status of males. We validated an epiandrosterone EIA for male cheetahs by performing a testosterone radiometabolism study followed by high-performance liquid chromatography (HPLC) analyses and excluding possible cross-reactivities with androgenic metabolites not derived from testosterone metabolism. The physiological and biological relevance of the epiandrosterone EIA was validated by demonstrating (1) a significant increase in fTM concentrations within one day in response to a testosterone injection, (2) a significant increase in fTM concentrations within one day in response to a gonadotropin-releasing hormone (GnRH) injection, which failed following a placebo injection, and (3) significant differences in fTM concentrations between adult male and adult female cheetahs and between adult and juvenile male cheetahs of a free-ranging population. Finally, we demonstrated stability of fTM concentrations measured in faecal samples exposed to ambient temperatures up to 72h. Our results clearly demonstrate that the epiandrosterone EIA is a reliable non-invasive method to monitor testicular activity in male cheetahs. PMID- 26828821 TI - A test of athletic internalisation as a mediator in the relationship between sociocultural influences and body dissatisfaction in women. AB - The tripartite model has been an important and empirically supported theoretical model positing that the influence of peers, family, and media leads women to internalise the thin societal body ideal. This internalisation in turn leads women to experience body dissatisfaction. Recently, a new societal 'athletic ideal' for women has emerged, which promotes a body frame with pronounced lean muscle mass. This study tested the role of the athletic ideal in the tripartite model of influence with a sample of 421 women aged 17-40 years. Athletic ideal internalisation was neither found to be associated with body dissatisfaction, nor act as a mediator in the relationship between sociocultural influences and body dissatisfaction. Although more research is required, the results of this study suggest that for this cross-sectional sample of women, internalisation of an athletic and muscular, rather than thin ideal, may be less detrimental to body satisfaction. PMID- 26828822 TI - A longitudinal study of 340 young people with or without a visible difference: The impact of teasing on self-perceptions of appearance and depressive symptoms. AB - Previous research in both the general population and in those with a visible facial difference has identified potential associations between teasing, dissatisfaction with appearance and emotional distress. However, most studies are based on cross-sectional and retrospective methodology, restricting the interpretation of findings. The present study explored the longitudinal impact of perceived teasing on satisfaction with appearance and depressive symptoms in young people with and without a visible congenital condition. Routine psychological assessments were conducted at ages 10 and 16 years (N=340). Experiences of teasing after the age of 10 significantly impacted on appearance evaluations and depressive symptoms in adolescent females. The impact of teasing on adolescent males was possibly counteracted by reports of more positive social experiences. Early identification of perceived teasing in all children to prevent the development of emotional problems and dissatisfaction with appearance is of vital importance. PMID- 26828823 TI - Evaluating the Impact of Breastfeeding on Rotavirus Antigenemia and Disease Severity in Indian Children. AB - OBJECTIVES: To evaluate the contribution of breastfeeding to Rotavirus (RV) induced antigenemia and/or RNAemia and disease severity in Indian children (<2 yrs age). METHODS: Paired stool and serum samples were collected from (a) hospitalized infants with diarrhea (n = 145) and (b) healthy control infants without diarrhea (n = 28). Stool RV-antigen was screened in both groups by commercial rapid-test and enzyme immunoassay. The disease severity was scored and real-time-PCR was used for viral-load estimation. Serum was evaluated for RV antigenemia by EIA and RV-RNAemia by RT-PCR. Data was stratified by age-group and breastfeeding status and compared. RESULTS: Presence of RV-antigenemia and RV RNAemia was positively related with presence of RV in stool. Disease severity and stool viral-load was significantly associated with RV-antigenemia [(r = 0.74; CI:0.66 to 0.84; P<0.0001,R2 = 0.59) and (r = -0.55; CI:-0.68 to -0.39; P<0.0001,R2 = 0.31) respectively], but not with RV-RNAemia. There was significant reduction in RV-antigenemiarate in the breast-fed group compared to non-breastfed infants, especially in 0-6 month age group (P<0.001). Non-breastfed infants were at risk for RV-antigenemia with severe disease manifestations in form of high Vesikari scores correlating with high fever, more vomiting episodes and dehydration. CONCLUSION: RV-antigenemia was common in nonbreastfed children with severe RV-diarrhea and correlated with stool RV-load and disease severity. PMID- 26828824 TI - Addressing defeatist beliefs in work rehabilitation. AB - BACKGROUND: Adults with serious mental illness (SMI) may struggle with expectations of failure in vocational rehabilitation. These expectations can be global and trait-like or performance-specific and related to ability. AIMS: To date, it has not been examined whether global or performance-specific defeatist beliefs are related to functional outcomes. METHOD: The Indianapolis Vocational Intervention Program (IVIP) is a CBT intervention used to address expectations of failure and improve work performance. We examined the relationships between defeatist beliefs, self-esteem, social functioning, and work behaviors in 54 adults with SMI who completed IVIP within a work therapy program. RESULTS: Baseline work-specific defeatist beliefs were related to baseline self-esteem, employment attitude, and work behaviors. Decline in work-specific defeatist beliefs was associated with better social functioning, self-esteem, and work behaviors. Decline in global defeatist beliefs was only associated with improvements in social functioning. CONCLUSIONS: Performance-specific expectations about work may be an appropriate therapeutic target to enhance work outcome in SMI. PMID- 26828825 TI - Efficacy of Rosmarinus officinalis leaves extract against cyclophosphamide induced hepatotoxicity. AB - Context Cyclophosphamide (CTX) is used to treat different cancer types, although it causes severe hepatotoxicity due to its oxidative stress effect. Rosmarinus officinalis, L. (Lamiaceae) has a therapeutic potential against hepatotoxicity due to its antioxidant activity. Objective The objective of this study is to investigate the phytochemical analysis of the methanol extract of Rosmarinus officianalis leaves (MEROL) and its efficacy against CTX-induced hepatotoxicity. Materials and methods The phytochemical analyses were assessed spectrophotometericaly. To assess the MEROL efficacy, 72 Swiss albino mice were divided into six groups. Group 1 was control, groups 2 and 3 included mice which were injected intraperitoneally (i.p.) with 100 or 200 mg/kg of MEROL at days 1, 4, 7, 10, 13 and 16; group 4 was injected (i.p.) with CTX (200 mg/kg) at day 17, groups 5 and 6 were injected (i.p.) with MEROL as groups 3 and 4 followed by 200 mg/kg CTX at day 17, respectively. At day 22, six mice from each group were sacrificed and the others were sacrificed at day 37. Results MEROL has a high content of total phenolics, saponins, total antioxidant capacity and DPPH radical scavenging activity. The median lethal dose (LD50) value of MEROL was 4.125 g/kg b.w. The inhibitory concentration 50 (IC50) value for DPPH radical scavenging was 55 MUg/mL. Pretreatment with 100 mg/kg MEROL for 16 d ameliorated CTX-induced hepatotoxicity represented in lowering the levels of the aspartate aminotransferase (AST) and lipid profile and minimizing the histological damage. Conclusions Pretreatment with 100 mg/kg b.w. MEROL mitigated CTX-induced hepatotoxicity due to its antioxidant activity. PMID- 26828827 TI - Detrimental Effect of Phenol Red on the Vitrification of Cat (Felis catus) Ovarian Tissue. AB - The aim of this study was to investigate the effects of different media with or without phenol red or the antioxidant trolox on the successful vitrification of feline ovarian tissue. In a first experiment, ovarian cortical pieces from three cats were vitrified in solutions of Roswell Park Memorial Institute (RPMI)-1640 medium, Minimum Essential Medium, Dulbecco's modified Eagle's medium, or Tissue Culture Medium 199 as basic medium, supplemented or not with 50 MUM of trolox, all containing 40% ethylene glycol (EG) and 1 M of sucrose. RPMI-1640 (phenol red free) without trolox was the only medium that preserved the percentage of morphologically normal preantral follicles similar to control (80%). The main difference between RPMI-1640 and the other media was the absence of phenol red and CaCl2. In a second experiment, ovarian cortical pieces from three cats were vitrified in a solution containing RPMI-1640 as basic medium, 40% EG, 1 M of sucrose, supplemented or not with phenol red or CaCl2 alone, or in combination. It was observed that phenol red supplementation led to follicular degeneration. Finally, to evaluate the interaction between phenol red and the cryoprotectant agent (i.e., EG), ovarian tissue was exposed to RPMI-1640 supplemented with phenol red and EG at different concentrations (10%, 20%, or 40%). There was an inverse relationship between EG concentration and free phenol red in the medium after exposure. It is suggested that vitrification of feline ovarian tissue should be performed in a phenol red-free medium. Medium supplementation with 50 MUM of trolox was deleterious for follicular morphology. PMID- 26828826 TI - Pluripotency markers are differentially induced by MEK inhibition in thyroid and melanoma BRAFV600E cell lines. AB - Oncogenic mutations in BRAF are common in melanoma and thyroid carcinoma and drive constitutive activation of the MAPK pathway. Molecularly targeted therapies of this pathway improves survival compared to chemotherapy; however, responses tend to be short-lived as resistance invariably occursCell line models of melanoma and thyroid carcinoma, +/- BRAF(V600E) activating mutation, were treated with the MEK inhibitor PD0325901. Treated and naive samples were assayed for expression of key members of the MAPK pathway. Global microRNA expression profiling of naive and resistant cells was performed via next generation sequencingand indicated pluripotency pathways in resistance. Parental cell lines were progressed to holoclones to confirm the miRNA stemness profileMembers of the MIR302/373/374/520 family of embryonic stem cell specific cell cycle regulating (ESCC) microRNAs were identified as differentially expressed between resistant BRAF(V600E) melanoma and thyroid cell lines. Upregulated expression of gene and protein stemness markers, upregulated expression of MAPK pathway genes and downregulation of the ESCC MIR302 cluster in BRAF(V600E) melanoma indicated an increased stem-like phenotype in resistant BRAF(V600E) melanoma. Conversely, downregulated expression of gene and protein stemness markers, downregulated expression of MAPK pathway genes, upregulation of the ESCC MIR520 cluster, reeexpression of cell surface receptors, and induced differentiation-associated morphology in resistant BRAF(V600E) indicate a differentiated phenotype associated with MEK inhibitor resistance in BRAF(V600E) thyroid cellsThe differential patterns of resistance observed between BRAF(V600E) melanoma and thyroid cell lines may reflect tissue type or de novo differentiation, but could have significant impact on the response of primary and metastatic cells to MEK inhibitor treatment. This study provides a basis for the investigation of the cellular differentiation/self-renewal access and its role in resistance to MEK inhibition. PMID- 26828828 TI - A response to Mimics of child abuse: Can choking explain abusive head trauma? [35 (2015) 33-37]. AB - In the recently published article in this journal, "Mimics of Child Abuse: Can Choking Explain Abusive Head Trauma?",(1) the author chose to revisit a discussion prompted by a case report from 5 years ago which was inappropriate in his opinion. He went further to suggest that bringing an unvalidated mechanism of injury into the legal setting "obstructs justice", is a "further victimization of the child", and is a "travesty of justice".(1) Given the "Shaken Baby Syndrome: Rotational Cranial Injuries" has always been only an unvalidated hypothesis lacking experimental confirmation, the exploring of alternative injury mechanisms should be entirely appropriate. In 2010, the post publication discussion ended with a challenge to the American Academy of Pediatrics Committee on Child Abuse and Neglect (AAP COCAN) to either support the pure shaking mechanism with quality EBMS or eliminate any positive support for it from any official policy statement until the exact nature of each injury that pure abusive shaking has the potential to cause is clearly defined and supported with quality experimental research.(4) Since this is an area of acknowledged controversy by the AAP, it is appropriate to examine the evidence based experimental literature that has emerged over the last five years that is relevant to the abusive shaking hypothesis and the hypothesis of any primary brain-lethal hypoxic event leading to the findings of retinal hemorrhages, extra-axial bleeding, and brain injury when an infant presents to medical attention after an Acute/Apparent Life Threatening Event. In that light, this review was undertaken. PMID- 26828829 TI - Amyloid-beta-Secondary Structure Distribution in Cerebrospinal Fluid and Blood Measured by an Immuno-Infrared-Sensor: A Biomarker Candidate for Alzheimer's Disease. AB - The misfolding of the Amyloid-beta (Abeta) peptide into beta-sheet enriched conformations was proposed as an early event in Alzheimer's Disease (AD). Here, the Abeta peptide secondary structure distribution in cerebrospinal fluid (CSF) and blood plasma of 141 patients was measured with an immuno-infrared-sensor. The sensor detected the amide I band, which reflects the overall secondary structure distribution of all Abeta peptides extracted from the body fluid. We observed a significant downshift of the amide I band frequency of Abeta peptides in Dementia Alzheimer type (DAT) patients, which indicated an overall shift to beta-sheet. The secondary structure distribution of all Abeta peptides provides a better marker for DAT detection than a single Abeta misfold or the concentration of a specific oligomer. The discrimination between DAT and disease control patients according to the amide I frequency was in excellent agreement with the clinical diagnosis (accuracy 90% for CSF and 84% for blood). The amide I band maximum above or below the decisive marker frequency appears as a novel spectral biomarker candidate of AD. Additionally, a preliminary proof-of-concept study indicated an amide I band shift below the marker band already in patients with mild cognitive impairment due to AD. The presented immuno-IR-sensor method represents a promising, simple, robust, and label-free diagnostic tool for CSF and blood analysis. PMID- 26828830 TI - Electrically driven single photon source at high temperature. AB - We present a theoretical model for an electrically driven single photon source operating at high temperatures. We show that decoherence, which is usually the main obstacle for operating single photon sources at high temperatures, ensures an efficient operation of the presented electrically driven single photon source at high temperatures. The single-photon source is driven by a single electron source attached to a heterostructure semiconductor nanoring. The electron's dynamics in the nanoring and the subsequent recombination with the hole is described by the generalized master equation with a Hamiltonian based on tight binding model, taking into account the electron-LO phonon interaction. As a result of decoherence, an almost 100% single photon emission with a strong antibunching behavior i.e. g(2)(0) << 1 at high temperature up to 300 K is achieved. PMID- 26828831 TI - Similarity in relationships as niche construction: Choice, stability, and influence within dyads in a free choice environment. AB - A series of field studies focused on the role of similarity as niche construction in friendships. Using a free-range dyad harvest method, we collected 11 independent samples with 1,523 interacting pairs, and compared dyad members' personality traits, attitudes, values, recreational activities, and alcohol and drug use. Within-dyad similarity was statistically significant on 86% of variables measured. To determine whether similarity was primarily attributable to niche construction (i.e., selection) or social influence, we tested whether similarity increased as closeness, intimacy, discussion, length of relationship, and importance of the attitude increased. There were no effects on similarity of closeness, relationship length, or discussion of the attitude. There were quite modest effects of intimacy, and a reliable effect of the shared importance of the attitude. Because relationship length, intimacy, closeness, and discussion can all serve as markers of opportunity for, or potency of social influence, these data are consistent with the "niche construction" account of similarity. In 2 follow-up controlled longitudinal field studies, participants interacted with people they did not know from their large lecture classes, and at a later time completed a survey of attitudes, values, and personality traits. Interacting pairs were not more similar than chance, but for the 23% of dyads that interacted beyond the first meeting, there was significant similarity within dyad members. These 2 lines of inquiry converge to suggest that similarity is mainly due to niche construction, and is most important in the early stages of a relationship; its importance to further relationship development wanes. (PsycINFO Database Record PMID- 26828832 TI - The Power of wE--Engaging, Empowering. PMID- 26828833 TI - Leadership and Staff Engagement: An Essential Link. PMID- 26828834 TI - Leader Empowering Behaviours and Work Engagement: The Mediating Role of Structural Empowerment. AB - Reports of poor working conditions persist amid ongoing healthcare restructuring. Simultaneously, nursing shortage threats continue as the nursing population ages. Leadership strategies that create empowering working conditions are likely to retain nurses who are eligible to retire, and attract future nurses to the profession. Several studies have focused on leader behaviours and structural empowerment in recent years and how these impact the work environment and staff engagement. Correlations among leader empowering behaviours, structural empowerment and work engagement have been demonstrated (Laschinger et al. 1999; Peachey 2002); however, there is a gap in the empirical literature as to how leader empowering behaviours influence nurses' work engagement by creating structurally empowering work environments. Kanter's (1977, 1993) structural empowerment theory was used to test this proposition using data from a cross sectional study of 322 Ontario staff nurses. Mediation analysis revealed that structural empowerment partially mediated the influence of leader empowering behaviours on work engagement. The implications for healthcare managers and leaders are discussed with a view to the recruitment and retention of nursing staff, by fostering greater work engagement. PMID- 26828835 TI - Identifying Strategies to Decrease Overtime, Absenteeism and Agency Use: Insights from Healthcare Leaders. AB - INTRODUCTION: Working overtime, absenteeism and agency use can negatively impact working environments, the health of staff and patient outcomes, and increase healthcare costs. The purpose of this study was to explore how healthcare leaders in Ontario hospitals implement and sustain best practices that advance workforce stability within their organization. METHODS: Qualitative study design using semi structured interviews and thematic analysis. RESULTS: Participants included 23 healthcare leaders from 16 hospital sites. Two main themes emerged: (1) enacting proactive human resource practices and (2) having strong, caring and strategic leaders that create learning and supportive work environments. A number of sub themes identified were reported through narratives stratified according to size (small/large) and performance (low/high) of each site. CONCLUSION: Insights gained from this study may offer healthcare leaders strategies to maximize the nursing workforce and minimize overtime, absenteeism and agency use to ensure safe, efficient and quality healthcare. PMID- 26828836 TI - Employee (Dis)Engagement: Learning from Nurses Who Left Organizational Jobs for Independent Practice. AB - Employee engagement is of growing interest in healthcare organizations. Engaged employees give an extra measure of effort to contribute to organization goals, whereas disengaged employees withdraw, have lower performance and are more likely to leave their jobs. The aim of this ethnographic study was, in part, to explore the reasons why high-calibre nurses became disengaged from their work and opted to leave their hospital-based employment in favour of independent practice, as well as to consider the organizational conditions that influenced their desire to leave. The findings revealed that nurses left their hospital-based jobs because of health system change, job characteristics, working conditions and lack of respect, which relate closely to the antecedents of employee engagement. Employee engagement can be fostered through organizational support, trust-building management behaviour and transformational leadership. PMID- 26828837 TI - Creating Engagement through Purpose and Meaning. AB - Nursing engagement is a critical issue facing healthcare organizations today. There is significant evidence linking engagement with both clinical and organizational outcomes. The three papers in this special focus (Cziraki and Laschinger 2015; Jeffs et al. 2015; Stackle-Wall 2015) each raise important points, perspectives and strategies to enhance engagement. PMID- 26828838 TI - A Systematic Review of the Cost-Effectiveness of Clinical Nurse Specialists and Nurse Practitioners in Inpatient Roles. AB - The objective of this systematic review was to synthesize the evidence of the effectiveness and cost-effectiveness of clinical nurse specialists (CNSs) and nurse practitioners (NPs) working in alternative or complementary roles in inpatient settings. Those in alternative roles substitute for another provider and deliver similar services. Those in complementary roles deliver additional services to meet patient health needs. We searched 10 electronic databases, reference lists, pertinent journals and websites from 1980 to July 2012 with no language, publication or geographical restrictions. Study identification and assessment were completed independently by two-member teams. Internal validity was assessed using the Cochrane Risk of Bias tool. The quality of the economic analysis was evaluated using the Quality of Health Economic Studies (QHES) instrument. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess outcome-specific quality of evidence. Three dated trials evaluated CNS and NP inpatient roles; they were conducted in North America and included 488 adults and 821 neonates. In one study, CNSs in complementary provider roles, when compared with usual care, were equally effective with equal resource use (very low-quality evidence). In two studies, NPs in alternative roles, when compared with physicians, were equally effective with equal-to-more resource use and equal costs (low- to moderate quality evidence). The quality of the economic analyses was poor. Only three dated studies were identified. More research is needed to determine cost effectiveness and inform policies and decisions related to the implementation of CNSs and NPs working exclusively in inpatient roles. PMID- 26828840 TI - Optic Atrophy in a Patient With Atypical Pantothenate Kinase-Associated Neurodegeneration. AB - Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive neurodegeneration with brain iron accumulation and characterized by extrapyramidal signs, vision loss, and intellectual decline. PKAN is caused by mutations in the PANK2 gene, which codes for a mitochondrial enzyme that phosphorylates vitamin B5 in the first reaction of the coenzyme A biosynthetic pathway. Visual failure in this disorder is typically due to pigmentary retinopathy. Yet our patient, a 13-year-old girl with PKAN, developed bilateral optic atrophy and the appearance of the retina and electroretinography were normal. Optic atrophy is a rare finding in patients with PKAN. It is important for the clinician to consider PKAN in the differential diagnosis of patients presenting with signs of extrapyramidal dysfunction, cognitive decline, and vision loss because of optic atrophy. PMID- 26828839 TI - Implementation of an Electronic Data Collection Tool to Monitor Nursing-Sensitive Indicators in a Large Academic Health Sciences Centre. AB - BACKGROUND: Monitoring the quality of nursing care is essential to identify patients at risk, measure adherence to hospital policies and evaluate the effectiveness of best practice interventions. However, monitoring nursing sensitive indicators (NSI) is a challenge. Prevalence surveys are one method used by some organizations to monitor NSI, which are patient outcomes that are directly affected by the quantity or quality of nursing care that the patient receives. OBJECTIVE: The aim of this paper is to describe the development of an innovative electronic data collection tool to monitor NSI. METHODS: In the preliminary development work, we designed a mobile computing application with pre populated patient census information to collect the nursing quality data. In subsequent phases, we refined this process by designing an electronic trigger using The Ottawa Hospital's Patient Safety Learning System, which automatically generated a case report form for each inpatient based on the hospital's daily patient census on the day of the prevalence survey. OBSERVATIONS: Both of these electronic data collection tools were accessible on tablet computers, which substantially reduced data collection, analysis and reporting time compared to previous paper-based methods. The electronic trigger provided improved completeness of the data. CONCLUSION: This work leveraged the use of tablet computers combined with a web-based application for patient data collection at point of care. Overall, the electronic methods improved data completeness and timeliness compared to traditional paper-based methods. This initiative has resulted in the ability to collect and report on NSI organization-wide to advance decision-making support and identify quality improvement opportunities within the organization. PMID- 26828841 TI - Nutritional Optic Neuropathy Caused by Copper Deficiency After Bariatric Surgery. AB - A 47-year-old woman developed severe bilateral visual loss 4 years after a Roux en-Y gastric bypass and 24 years after vertical banded gastroplasty. Her serum copper level was 35 MUg/dL (normal, 80-155 MUg/dL). She was prescribed elemental copper tablets. Because her methylmalonic acid was slightly elevated, she received vitamin B12 injections as well. Five weeks later, she reported that her vision had improved and, at 10 months, her vision had recovered from 20/400 bilaterally to 20/25 in each eye. This case highlights the importance of checking copper levels in addition to the "more routine" vitamin levels, such as B1, B6, B12, E, and serum folate in patients with suspected nutritional optic neuropathy after bariatric surgery, particularly if it involved a bypass procedure. PMID- 26828842 TI - Neuro-Ophthalmology of Space Flight. AB - BACKGROUND: To describe the history, clinical findings, and possible pathogenic etiologies of the constellation of neuro-ophthalmic findings discovered in astronauts after long-duration space flight and to discuss the terrestrial implications of such findings. EVIDENCE ACQUISITION: Retrospective review of published observational, longitudinal examination of neuro-ophthalmic findings in astronauts after long-duration space flight; analysis of postflight questionnaires regarding in-flight vision changes in approximately 300 additional astronauts; and hypothesis generating for developing possible future countermeasures and potential implications for neuro-ophthalmic disorders on Earth. Astronauts with neuro-ophthalmic findings, which were not present at the start of a space flight mission and only seen on return from long-duration space missions to the International Space Station, will be discussed. RESULTS: After 6 months of space flight, 7 astronauts had ophthalmic findings consisting of optic disc edema in 5, globe flattening in 5, choroidal folds in 5, cotton-wool spots in 3, nerve fiber layer thickening detected by optical coherence tomography in 6, and decreased near vision in 6. Five of 7 astronauts with near vision complaints had a hyperopic shift >=+0.50 diopters (D) between pre-/post-mission spherical equivalent refraction in 1 or both eyes (range, +0.50 to +1.75 D). These 5 astronauts showed globe flattening on magnetic resonance imaging. A total of 6 lumbar punctures have been performed to date (4 in the originally described cohort) and documented opening pressures of 18, 22, 21, 21.5, 28, and 28.5 cm H2O. These were performed at 8, 66, 19, 7, 12, and 57 days after mission, respectively. The 300 postflight questionnaires documented that approximately 29% and 60% of astronauts on short-duration and long-duration missions, respectively, experienced a degradation in distant and near visual acuity. Some of these vision changes remain unresolved for years after flight. Several possible pathogenic mechanisms, as well as potential countermeasures and discussion of possible terrestrial implications, are described. CONCLUSIONS: We previously hypothesized that the optic nerve and ocular changes that we described in astronauts may be the result of orbital and cranial cephalad fluid shifts brought about by prolonged microgravity exposure. The findings we reported previously and continue to see in astronauts may represent parts of a spectrum of ocular and cerebral responses to extended microgravity exposure. Future investigations hopefully will lead to countermeasures that can be used to eliminate or lessen the magnitude of these potentially harmful findings before long-duration space flight including the possibility of a manned mission to Mars. PMID- 26828843 TI - Visual Deterioration and Herniation of the Anterior Cerebral Artery: Unusual Presentation of an Empty Sella Syndrome Complicating Decompression of a Rathke Cleft Cyst. AB - Clinical manifestations of empty sella syndrome include hypopituitarism cerebrospinal fluid rhinorrhea, headache, and visual abnormalities. A 21-year-old woman reported a 6-month history of worsening vision 3 years after decompression of a sellar-suprasellar Rathke cleft cyst. Her magnetic resonance imaging (MRI) showed a well-defined recurrent cyst in the sellar-suprasellar region causing chiasmatic compression. She underwent an endonasal, endoscopic decompression of the cyst, with subsequent improvement in her vision. A postoperative computed tomography confirmed good decompression of the cyst. Ten days after surgery, she reported sudden loss of vision in both eyes. MRI revealed an empty sella with herniation of both anterior cerebral arteries and optic chiasm into the sella. She underwent transnasal packing of the sellar floor with fat graft and bone plaques, and experienced gradual improvement in vision in her right eye. PMID- 26828844 TI - Are Erectile Dysfunction Medications Causally Related to Nonarteritic Anterior Ischemic Optic Neuropathy? PMID- 26828845 TI - Oxygen-activated growth and bandgap tunability of large single-crystal bilayer graphene. AB - Bernal (AB)-stacked bilayer graphene (BLG) is a semiconductor whose bandgap can be tuned by a transverse electric field, making it a unique material for a number of electronic and photonic devices. A scalable approach to synthesize high quality BLG is therefore critical, which requires minimal crystalline defects in both graphene layers and maximal area of Bernal stacking, which is necessary for bandgap tunability. Here we demonstrate that in an oxygen-activated chemical vapour deposition (CVD) process, half-millimetre size, Bernal-stacked BLG single crystals can be synthesized on Cu. Besides the traditional 'surface-limited' growth mechanism for SLG (1st layer), we discovered new microscopic steps governing the growth of the 2nd graphene layer below the 1st layer as the diffusion of carbon atoms through the Cu bulk after complete dehydrogenation of hydrocarbon molecules on the Cu surface, which does not occur in the absence of oxygen. Moreover, we found that the efficient diffusion of the carbon atoms present at the interface between Cu and the 1st graphene layer further facilitates growth of large domains of the 2nd layer. The CVD BLG has superior electrical quality, with a device on/off ratio greater than 10(4), and a tunable bandgap up to ~100 meV at a displacement field of 0.9 V nm(-1). PMID- 26828846 TI - A reconfigurable waveguide for energy-efficient transmission and local manipulation of information in a nanomagnetic device. AB - Spin-wave-based devices promise to usher in an era of low-power computing where information is carried by the precession of the electrons' spin instead of dissipative translation of their charge. This potential is, however, undermined by the need for a bias magnetic field, which must remain powered on to maintain an anisotropic device characteristic. Here, we propose a reconfigurable waveguide design that can transmit and locally manipulate spin waves without the need for any external bias field once initialized. We experimentally demonstrate the transmission of spin waves in straight as well as curved waveguides without a bias field, which has been elusive so far. Furthermore, we experimentally show a binary gating of the spin-wave signal by controlled switching of the magnetization, locally, in the waveguide. The results have potential implications in high-density integration and energy-efficient operation of nanomagnetic devices at room temperature. PMID- 26828847 TI - Spintronics: Nanomagnonics around the corner. PMID- 26828848 TI - Surface functionalization of two-dimensional metal chalcogenides by Lewis acid base chemistry. AB - Precise control of the electronic surface states of two-dimensional (2D) materials could improve their versatility and widen their applicability in electronics and sensing. To this end, chemical surface functionalization has been used to adjust the electronic properties of 2D materials. So far, however, chemical functionalization has relied on lattice defects and physisorption methods that inevitably modify the topological characteristics of the atomic layers. Here we make use of the lone pair electrons found in most of 2D metal chalcogenides and report a functionalization method via a Lewis acid-base reaction that does not alter the host structure. Atomic layers of n-type InSe react with Ti(4+) to form planar p-type [Ti(4+)n(InSe)] coordination complexes. Using this strategy, we fabricate planar p-n junctions on 2D InSe with improved rectification and photovoltaic properties, without requiring heterostructure growth procedures or device fabrication processes. We also show that this functionalization approach works with other Lewis acids (such as B(3+), Al(3+) and Sn(4+)) and can be applied to other 2D materials (for example MoS2, MoSe2). Finally, we show that it is possible to use Lewis acid-base chemistry as a bridge to connect molecules to 2D atomic layers and fabricate a proof-of-principle dye sensitized photosensing device. PMID- 26828849 TI - Magnetic domain walls as reconfigurable spin-wave nanochannels. AB - In the research field of magnonics, it is envisaged that spin waves will be used as information carriers, promoting operation based on their wave properties. However, the field still faces major challenges. To become fully competitive, novel schemes for energy-efficient control of spin-wave propagation in two dimensions have to be realized on much smaller length scales than used before. In this Letter, we address these challenges with the experimental realization of a novel approach to guide spin waves in reconfigurable, nano-sized magnonic waveguides. For this purpose, we make use of two inherent characteristics of magnetism: the non-volatility of magnetic remanence states and the nanometre dimensions of domain walls formed within these magnetic configurations. We present the experimental observation and micromagnetic simulations of spin-wave propagation inside nano-sized domain walls and realize a first step towards a reconfigurable domain-wall-based magnonic nanocircuitry. PMID- 26828850 TI - Planning Treatment and Assessing Recovery in Participants With Dual Diagnosis: Preliminary Evaluation of a New Clinical Tool. AB - OBJECTIVE: Integrated treatment for people with co-occurring mental illness and substance use disorder would be enhanced by a simple, recovery-oriented instrument to plan treatment and monitor progress toward dual recovery. This paper describes the development of a clinical instrument, the WestBridge Dual Recovery Inventory, and presents a preliminary evaluation of its usability. METHODS: In collaboration with participants in treatment, family members, clinicians, and program leaders, we developed an inventory on dual recovery and then examined its utility through a series of iterative steps. First, we tested the inventory for inter-rater reliability among 10 program participants (rated independently by the first and last author). Second, we examined concordance by having a separate group of 10 program participants and their care managers complete the inventory independently. Third, we observed 3 care managers and 10 participants working together to complete the inventory as part of routine care during the quarterly assessment; we evaluated shared decision making based on the process they used to resolve differences and on a brief survey completed by program participants as the end of the session. Finally, to measure the inventory's capacity to detect change over time, we analyzed the ratings from admission to one year for 43 participants with quarterly assessments available for that time period. RESULTS: The WestBridge Dual Recovery Inventory assesses 14 domains of recovery, each rated on 5-point scales. Inter-rater reliability was high (Kappa = .82 to 1.00); agreement between independent ratings by care managers and participants varied considerably (Kendall's tau = -.83 to +.87); and collaborative ratings demonstrated high scores on shared decision making. Participants improved significantly on 11 of 14 domains during the initial residential treatment phase (admission to six months) and sustained gains during outpatient assertive community treatment (6 to 12 months). CONCLUSIONS: This preliminary assessment of the WestBridge Dual Recovery Inventory suggests that it reliably assesses dual recovery, facilitates shared decision making, and captures changes over time. The inventory appears to be usable, well received by participants and care managers, specific for program goals, and sensitive to changes in the participants. Recovery measures may need to be program-specific. PMID- 26828851 TI - Bevacizumab beyond disease progression for advanced non-small cell lung cancer: Does persistence have its rewards? PMID- 26828852 TI - Alteration of amiloride-sensitive salt taste nerve responses in aldosterone/NaCl induced hypertensive rats. AB - Salt taste sensitivity is related to physiological condition, and declined in hypertensive patients. However, little is known about the mechanism underlying changes in salt taste sensitivity during the development of hypertension. This is largely due to lack of an appropriate animal model which shows the decline of salt taste sensitivity caused by hypertension. Previous studies have suggested that one of main causes of salt-sensitive hypertension is dysfunction of the renin-angiotensin-aldosterone system (RAAS). To examine the involvement of RAAS in modulation of salt taste sensitivity, we utilized aldosterone/NaCl-treated rats as a well-established model of salt-sensitive hypertension caused by RAAS dysfunction. Amount of sodium intake in aldosterone/NaCl-treated rats was higher than that in control rats. In addition to behavioral changes, the amiloride sensitive salt taste nerve responses in aldosterone/NaCl-treated rats were remarkably lower by approximately 90% than those in the other groups. Moreover, alphaENaC mRNA expression in the epithelium of circumvallate papillae was significantly low in aldosterone/NaCl-treated rats. Thus, RAAS modulates salt taste system as is case in hypertensive patients. This report is to our knowledge the first to describe an animal model with decline of amiloride-sensitive salt taste nerve responses by RAAS dysfunction-mediated salt-sensitive hypertension. PMID- 26828853 TI - Nanospherical like reduced graphene oxide decorated TiO2 nanoparticles: an advanced catalyst for the hydrogen evolution reaction. AB - Modification of titanium dioxide (TiO2) for H2 generation is a grand challenge due to its high chemical inertness, large bandgap, narrow light-response range and rapid recombination of electrons and holes. Herein, we report a simple process to prepare nanospherical like reduced graphene oxide (NS-rGO) decorated TiO2 nanoparticles (NS-rGO/TiO2) as photocatalysts. This modified TiO2 sample exhibits remarkably significant improvement on visible light absorption, narrow band gap and efficient charge collection and separation. The photocatalytic H2 production rate of NS-rGO/TiO2 is high as 13996 MUmol g(-1) h(-1), which exceeds that obtained on TiO2 alone and TiO2 with parallel graphene sheets by 3.45 and 3.05 times, respectively. This improvement is due to the presence of NS-rGO as an electron collector and transporter. The geometry of NS-rGO should be effective in the design of a graphene/TiO2 composite for photocatalytic applications. PMID- 26828854 TI - Simulating Human and Environmental Exposure from Hand-Held Knapsack Pesticide Application: Be-WetSpa-Pest, an Integrative, Spatially Explicit Modeling Approach. AB - This paper presents an integrative and spatially explicit modeling approach for analyzing human and environmental exposure from pesticide application of smallholders in the potato-producing Andean region in Colombia. The modeling approach fulfills the following criteria: (i) it includes environmental and human compartments; (ii) it contains a behavioral decision-making model for estimating the effect of policies on pesticide flows to humans and the environment; (iii) it is spatially explicit; and (iv) it is modular and easily expandable to include additional modules, crops, or technologies. The model was calibrated and validated for the Vereda La Hoya and was used to explore the effect of different policy measures in the region. The model has moderate data requirements and can be adapted relatively easily to other regions in developing countries with similar conditions. PMID- 26828855 TI - Fabrication highly dispersed Fe3O4 nanoparticles on carbon nanotubes and its application as a mimetic enzyme to degrade Orange II. AB - Fe3O4 nanoparticles were grown in situ on carbon nanotubes (CNTs) by a solvothermal method. The Fe3O4/CNTs composites were characterised by the Brunauer Emmett-Teller method and transmission electron microscopy. The results indicated that the Fe3O4 nanoparticles were uniformly deposited on CNTs, and the average diameter was approximately 7.0 nm. The Fe3O4/CNTs were applied as an enzyme mimetic to decompose Orange II, and the decomposing conditions were optimised. At 500 mg L(-1) of Fe3O4/CNTs in the presence of 15.0 mmol L(-1) of H2O2, at 30 degrees C, it degraded 94.0% of Orange II (0.25 mmol L(-1), pH = 3.5), showing higher catalytic activity than pure Fe3O4 nanoparticles. The high activity was attributed to the uniform Fe3O4 nanoparticles growing on the side walls of the CNTs and the synergetic effect between Fe3O4 and CNTs. The Fe3O4/CNTs maintained their activity at temperatures as high as 65 degrees C. The Fe3O4/CNTs presented high reusability and stability even after eight uses. These data proved that the Fe3O4/CNTs-catalysed degradation is a promising technique for wastewater treatment. Fe3O4 nanoparticles were grown in situ on carbon nanotubes (CNTs) by a solvothermal method. The Fe3O4/CNTs was applied as a mimetic enzyme to decompose Orange II. The Fe3O4/CNTs were collected after the reaction by applying an external magnetic field and can use repeatedly. PMID- 26828856 TI - N->Sn-Coordinated Stannaoxidoborates Containing a SnB4O6 Unit. AB - We report here the synthesis of new N->Sn-coordinated stannaoxidoborates H[LSnB4O6R4] {L = [2,6-(Me2NCH2)C6H3](-) and R = Ph (6), 4-Br-Ph (7), 3,5-(CF3)2 Ph (8), and 4-CHO-Ph (9)} containing a nonsymmetric SnB4O6 unit. Compounds 6-9 represent new derivatives of the pentaborates [B5O6R4](-) in which the central boron is substituted by a tin atom. Compounds 6-9 were characterized by means of elemental analysis, electrospray ionization mass spectrometry, and NMR spectroscopy and in the case of 6-8 also by single-crystal X-ray diffraction analysis. The structures of N->Sn-coordinated stannaoxidoborates 6-8 consist of a spirobicyclic arrangement, with two six-membered SnB2O3 rings at the tin atom providing the new stannaoxidoborate [LSnB4O6R4](-) motif, which is compensated for by the proton atom coordinated to the Me2N group of the ligand L. The linear and thermal properties of 6-9 were studied with the help of electronic absorption spectra and differential scanning calorimetry. In addition, the presence of the nonsymmetric stannaoxidoborate SnB4O6 unit in 6, 7, and 9 prompted us to investigate their second-order nonlinear-optical properties. PMID- 26828857 TI - Group compositional changes impact the social and feeding behaviors of captive hamadryas baboons (Papio hamadryas hamadryas). AB - The formation and modification of social groups in captivity are delicate management tasks. The ability for personnel to anticipate changes in group dynamics following compositional changes can increase the likelihood of successful management with minimized injury or social instability. Hamadryas baboons (Papio hamadryas hamadryas) have a distinctive multi-level social system comprising of one-male units (OMUs) that can make it difficult to apply knowledge from other primates' multi-female/multi-male social structure to changes imposed onto captive hamadryas baboon groups. We conducted an observational study of the behavioral impacts following the introduction of two females into the group of hamadryas baboons at the Wildlife Conservation Society's Prospect Park Zoo in NY to test hypotheses about the relationships between changes in group composition and social and feeding behavior. Generalized linear mixed models demonstrated that social interactions significantly increased following the compositional changes, even in groups that only experienced member removals. The increase in affiliative social behavior observed suggests that during times of social stress or uncertainty, hamadryas baboons may employ social behavior as a tension reducing mechanism to negotiate relationships as opposed to using aggression to engage in competitions for ranks and resources. The observed response to compositional changes implies that hamadryas baboons may respond with less aggression than do other Old World monkey species and that levels of affiliative behavior may be a more accurate metric for evaluating introduction success in hamadryas baboons. PMID- 26828858 TI - The use of advanced airway management devices in clinical practice. PMID- 26828859 TI - Exogenous pulmonary surfactant prevents the development of intra-abdominal adhesions in rats. AB - Intra-abdominal adhesions are major post-operative complications for which no effective means of prevention is available. We aimed to evaluate the efficacy of exogenous pulmonary surfactant administration in the prevention of post-operative abdominal adhesions. Rats were randomly assigned to undergo laparotomy (L) or gastroenterostomy (GE) and then treated with surfactant (groups L-S and GE-S, respectively). Intra-abdominal adhesions, collagen fibre content, metalloproteinase (MMP)-9, expression of growth factors (TGF-beta, KGF and VEGF), type III procollagen (PCIII) and pro-caspase 3, as well as isolectin B4 and ED1 positive cells expressing MMP-9, were evaluated. Groups treated with surfactant (GE-S and L-S) exhibited fewer adhesions. A significant reduction in collagen fibre content was observed in GE-S compared to GE animals (P < 0.001). In situ and gelatin zymography analysis showed higher MMP-9 expression and activity in the GE-S group compared to the GE group (P < 0.05). ED1-positive cell counts were significantly higher in the GE-S group (P < 0.001) than in the GE group. Virtually all cells positive for ED1 were MMP-9+. Double-labelling of MMP-9 with IB4 showed no significant differences between GE-S and GE groups. TGF-beta, KGF, PCIII and pro-caspase-3 mRNA expression decreased significantly in GE-S compared to GE animals (P < 0.05). Surfactant administration also reduced apoptosis in the GE-S group. These findings suggest that surfactant reduces the intra-abdominal adhesions triggered by laparotomy and gastrointestinal anastomosis, thus preventing fibrosis formation at the peritoneal surfaces. This preclinical study suggests an innovative treatment strategy for intra-abdominal adhesions with surfactant and to endorse its putative mechanism of action. PMID- 26828860 TI - Implication of zinc excess on soil health. AB - This study was undertaken to evaluate zinc's influence on the resistance of organotrophic bacteria, actinomyces, fungi, dehydrogenases, catalase and urease. The experiment was conducted in a greenhouse of the University of Warmia and Mazury (UWM) in Olsztyn, Poland. Plastic pots were filled with 3 kg of sandy loam with pHKCl - 7.0 each. The experimental variables were: zinc applied to soil at six doses: 100, 300, 600, 1,200, 2,400 and 4,800 mg of Zn(2+) kg(-1) in the form of ZnCl2 (zinc chloride), and species of plant: oat (Avena sativa L.) cv. Chwat and white mustard (Sinapis alba) cv. Rota. Soil without the addition of zinc served as the control. During the growing season, soil samples were subjected to microbiological analyses on experimental days 25 and 50 to determine the abundance of organotrophic bacteria, actinomyces and fungi, and the activity of dehydrogenases, catalase and urease, which provided a basis for determining the soil resistance index (RS). The physicochemical properties of soil were determined after harvest. The results of this study indicate that excessive concentrations of zinc have an adverse impact on microbial growth and the activity of soil enzymes. The resistance of organotrophic bacteria, actinomyces, fungi, dehydrogenases, catalase and urease decreased with an increase in the degree of soil contamination with zinc. Dehydrogenases were most sensitive and urease was least sensitive to soil contamination with zinc. Zinc also exerted an adverse influence on the physicochemical properties of soil and plant development. The growth of oat and white mustard plants was almost completely inhibited in response to the highest zinc doses of 2,400 and 4,800 mg Zn(2+) kg( 1). PMID- 26828861 TI - Cx43-Dependent Skeletal Phenotypes Are Mediated by Interactions between the Hapln1a-ECM and Sema3d during Fin Regeneration. AB - Skeletal development is a tightly regulated process and requires proper communication between the cells for efficient exchange of information. Analysis of fin length mutants has revealed that the gap junction protein Connexin43 (Cx43) coordinates cell proliferation (growth) and joint formation (patterning) during zebrafish caudal fin regeneration. Previous studies have shown that the extra cellular matrix (ECM) protein Hyaluronan and Proteoglycan Link Protein1a (Hapln1a) is molecularly and functionally downstream of Cx43, and that hapln1a knockdown leads to reduction of the glycosaminoglycan hyaluronan. Here we find that the proteoglycan aggrecan is similarly reduced following Hapln1a knockdown. Notably, we demonstrate that both hyaluronan and aggrecan are required for growth and patterning. Moreover, we provide evidence that the Hapln1a-ECM stabilizes the secreted growth factor Semaphorin3d (Sema3d), which has been independently shown to mediate Cx43 dependent phenotypes during regeneration. Double knockdown of hapln1a and sema3d reveal synergistic interactions. Further, hapln1a knockdown phenotypes were rescued by Sema3d overexpression. Therefore, Hapln1a maintains the composition of specific components of the ECM, which appears to be required for the stabilization of at least one growth factor, Sema3d. We propose that the Hapln1a dependent ECM provides the required conditions for Sema3d stabilization and function. Interactions between the ECM and signaling molecules are complex and our study demonstrates the requirement for components of the Hapln1a-ECM for Sema3d signal transduction. PMID- 26828863 TI - Proteome-Wide Identification of Lysine Succinylation in the Proteins of Tomato (Solanum lycopersicum). AB - Post-translational modification of proteins through lysine succinylation plays important regulatory roles in living cells. Lysine succinylation was recently identified as a novel post-translational modification in Escherichia coli, yeast, Toxoplasma gondii, HeLa cells, and mouse liver. Interestingly, only a few sites of lysine succinylation have been detected in plants to date. In this study, we identified 347 sites of lysine succinylation in 202 proteins in tomato by using high-resolution mass spectrometry. Succinylated proteins are implicated in the regulation of diverse metabolic processes, including chloroplast and mitochondrial metabolism. Bioinformatic analysis showed that succinylated proteins are evolutionarily conserved and involved in various cellular functions such as metabolism and epigenetic regulation. Moreover, succinylated proteins exhibit diverse subcellular localizations. We also defined six types of definitively conserved succinylation motifs. These results provide the first in depth analysis of the lysine succinylome and novel insights into the role of succinylation in tomato, thereby elucidating lysine succinylation in the context of cellular physiology and metabolite biosynthesis in plants. PMID- 26828862 TI - Extensive Recombination of a Yeast Diploid Hybrid through Meiotic Reversion. AB - In somatic cells, recombination between the homologous chromosomes followed by equational segregation leads to loss of heterozygosity events (LOH), allowing the expression of recessive alleles and the production of novel allele combinations that are potentially beneficial upon Darwinian selection. However, inter-homolog recombination in somatic cells is rare, thus reducing potential genetic variation. Here, we explored the property of S. cerevisiae to enter the meiotic developmental program, induce meiotic Spo11-dependent double-strand breaks genome wide and return to mitotic growth, a process known as Return To Growth (RTG). Whole genome sequencing of 36 RTG strains derived from the hybrid S288c/SK1 diploid strain demonstrates that the RTGs are bona fide diploids with mosaic recombined genome, derived from either parental origin. Individual RTG genome wide genotypes are comprised of 5 to 87 homozygous regions due to the loss of heterozygous (LOH) events of various lengths, varying between a few nucleotides up to several hundred kilobases. Furthermore, we show that reiteration of the RTG process shows incremental increases of homozygosity. Phenotype/genotype analysis of the RTG strains for the auxotrophic and arsenate resistance traits validates the potential of this procedure of genome diversification to rapidly map complex traits loci (QTLs) in diploid strains without undergoing sexual reproduction. PMID- 26828864 TI - Comparative systems genetics view of endometriosis and uterine leiomyoma: Two sides of the same coin? AB - Endometriosis (EM) and uterine leiomyoma (UL) are two most frequent benign tumors of monoclonal origin affecting about 30% of all women in their reproductive age. Modern molecular technologies have made a tremendous impact in understanding both disorders. Here is the first comparative analysis of molecular mechanisms underlying development of EM and UL as it looks from the platform of systems genetics. Similarities and differences of EM and UL at their incipient stages are enlightened with special emphasis on their gene networks, gene expression, and epigenetic regulation, of pathologic development. The analysis substantiates a new hypothesis postulating tumors as outgrowths of the stem cells with mesenchymal commitment lineage (mSC) which migrate from the endometrium/myometrium junctional zone of the uterus. Comparative analysis has revealed basic similarities of molecular pathogenesis of EM and UL suggesting molecular syntropy of both disorders. Peculiarities of the epigenetic landscape determining development of mSC may explain the existence of different clinical forms of EM and UL as well as their unique clinical manifestation. Some perspectives for practical and scientific application in EM and UL studies of this new hypothesis are outlined. PMID- 26828865 TI - Oral Administration of Electron-Beam Inactivated Rhodococcus equi Failed to Protect Foals against Intrabronchial Infection with Live, Virulent R. equi. AB - There is currently no licensed vaccine that protects foals against Rhodococcus equi-induced pneumonia. Oral administration of live, virulent R. equi to neonatal foals has been demonstrated to protect against subsequent intrabronchial challenge with virulent R. equi. Electron beam (eBeam)-inactivated R. equi are structurally intact and have been demonstrated to be immunogenic when administered orally to neonatal foals. Thus, we investigated whether eBeam inactivated R. equi could protect foals against developing pneumonia after experimental infection with live, virulent R. equi. Foals (n = 8) were vaccinated by gavaging with eBeam-inactivated R. equi at ages 2, 7, and 14 days, or gavaged with equal volume of saline solution (n = 4), and subsequently infected intrabronchially with live, virulent R. equi at age 21 days. The proportion of vaccinated foals that developed pneumonia following challenge was similar among the vaccinated (7/8; 88%) and unvaccinated foals (3/4; 75%). This vaccination regimen did not appear to be strongly immunogenic in foals. Alternative dosing regimens or routes of administration need further investigation and may prove to be immunogenic and protective. PMID- 26828866 TI - Photoresponsive hydrogel networks using melanin nanoparticle photothermal sensitizers. AB - Photoreconfigurable and photodegradable polymeric networks have broad utility as functional biomaterials for many applications in medicine and biotechnology. The vast majority of these functional polymers are synthesized using chemical moieties that may be cytotoxic in vivo. Materials synthesized from these substituents also pose unknown risk upon implantation and thus will encounter significant regulatory challenges prior to use in vivo. This work describes a strategy to prepare photodegradable hydrogel networks that are composed of well characterized synthetic polymers and natural melanin pigments found within the human body. Self-assembled networks of poly(l-lactide-co-glycolide)-poly(ethylene glycol) ABA triblock copolymers are doped with melanin nanoparticles to produce reconfigurable networks based on photothermal phase transitions. Self-assembled hydrogel networks with melanin nanoparticles exhibit a storage modulus ranging from 1.5 +/- 0.6 kPa to 8.0 +/- 7.5 kPa as measured by rheology. The rate of UV induced photothermal heating was non-monotonic and varied as a function of melanin nanoparticle loading. A maximum steady state temperature increase of 20.5 +/- 0.30 degrees C was measured. Experimental heating rates were in close agreement with predictions based on attenuation of light in melanins via photothermal absorption and Mie scattering. The implications of melanin nanoparticles on hydrogel network formation and light-induced disintegration were also characterized by rheology and dynamic light scattering. Taken together, this class of photoreconfigurable hydrogels represents a potential strategy for photodegradable polymers with increased likelihood for clinical translation. PMID- 26828867 TI - Metal-Induced Production of a Novel Bioadsorbent Exopolysaccharide in a Native Rhodotorula mucilaginosa from the Mexican Northeastern Region. AB - There is a current need to develop low-cost strategies to degrade and eliminate industrially used colorants discharged into the environment. Colorants discharged into natural water streams pose various threats, including: toxicity, degradation of aesthetics and inhibiting sunlight penetration into aquatic ecosystems. Dyes and colorants usually have complex aromatic molecular structures, which make them very stable and difficult to degrade and eliminate by conventional water treatment systems. The results in this work demonstrated that heavy metal resistant Rhodotorula mucilaginosa strain UANL-001L isolated from the northeast region of Mexico produce an exopolysaccharide (EPS), during growth, which has colorant adsorption potential. The EPS produced was purified by precipitation and dialysis and was then physically and chemically characterized by Scanning Electron Microscopy, Fourier Transform Infrared Spectroscopy, and chemical elemental analysis. Here, the ability of the purified EPS produced to adsorb methylene blue (MB), which served as a model colorant, is studied. MB adsorption by the EPS is found to follow Langmuir Adsorption Isotherm kinetics at 25 degrees C. Further, by calculating the Langmuir constant the adsorption capabilities of the EPS produced by the Rhodotorula mucilaginosa strain UANL-001L is compared to that of other adsorbents, both, microbially produced and from agroindustrial waste. The total adsorption capacity of the EPS, from the Rhodotorula mucilaginosa strain UANL-001L, was found to be two-fold greater than the best bioadsorbents reported in the literature. Finally, apart from determining which heavy metals stimulated EPS production in the strain, the optimal conditions of pH, heavy metal concentration, and rate of agitation of the growing culture for EPS production, was determined. The EPS reported here has the potential of aiding in the efficient removal of colorants both in water treatment plants and in situ in natural water streams. PMID- 26828868 TI - Idiopathic thoracic spinal epidural lipomatosis causing spinal cord compression. PMID- 26828869 TI - Matched-pair cohort study of 1-year patient-reported outcomes following pelvic fixation. AB - BACKGROUND CONTEXT: Pelvic fixation improves fusion and stability for thoracolumbar constructs that extend across the L5-S1 junction. No patient reported outcomes have been published to evaluate patients' functional outcomes following these procedures compared with pelvis-sparing procedures. PURPOSE: The goal of this study is to identify the effect of pelvic fixation on both objective and patient-reported outcomes. STUDY DESIGN/SETTING: This was a retrospective, matched cohort study. PATIENT SAMPLE: The sample comprised adult patients undergoing spine surgery at our institution who had complete 1-year postoperative follow-up. OUTCOME MEASURES: Patient-reported outcome instruments (Oswestry Disability Index [ODI], Short-Form 12-item survey, and EuroQol-5D) and objective measures (length of hospital stay, discharge disposition, postoperative complications, and readmission rates) were considered. METHODS: We identified patients in our outcomes registry undergoing instrumented spinal fusion involving the pelvis between October 2010 and May 2014 who had 1-year follow-up data. Nearest-neighbor 1:1 matched controls were identified using propensity scoring from the cohort of patients undergoing any spinal procedure which extended caudally to the lumbar spine or sacrum. Objective and patient-reported outcomes were compared between cases and controls. RESULTS: There were 44 patients who underwent spinal procedures involving the pelvis and had 1-year follow-up data. An equal number of controls were identified and had similar baseline demographic and clinical characteristics. No significant differences were found among operative variables or objective complication rates. Patients undergoing pelvic fixation had moderately greater improvement at 3 months as measured by ODI, but this difference was not present at 1 year. Other patient-reported outcome measures were equivocal between groups. CONCLUSIONS: This matched cohort study demonstrates that inclusion of the pelvis in spinal hardware constructs is not associated with increased complications and may slightly improve patient disability at 1 year. Given that pelvic fixation may reduce L5-S1 breakdown and improve biomechanics, surgeons should more readily include the pelvis in instrumented fusion procedures. PMID- 26828870 TI - Opportunistic fungi in lake water and fungal infections in associated human population in Dal Lake, Kashmir. AB - Natural habitats of opportunistic fungal pathogens are outside of the host; therefore, it is critically important to understand their ecology and routes of transmission. In this study, we investigated the presence of human pathogenic opportunistic fungi in lake water and incidence of fungal infections in associated population in Kashmir, India. Six hundred forty water samples were taken on seasonal basis from a wide network of sampling stations of the lake for an extended period of two years for screening their occurrence. The samples were inoculated onto rose bengal agar, malt extract agar, potato dextrose agar and other specified culture media supplemented with Chloramphenicol and Streptomycin followed by incubation at 37 degrees C. All the samples were positive for fungi, which were later identified by sequencing the rDNA internal transcribed spacer region aided by classical morphological culture techniques and physiological profiling. The whole process led to the isolation of sixteen species of opportunistic fungal pathogens belonging to genus Aspergillus, Candida, Penicillium, Cryptococcus, Fusarium, Rhizopus and Mucor in decreasing order of prevalence. Furthermore, 20% population (n = 384) of Dal inhabitants was examined for possible fungal infections and it was observed that only 8.07% individuals were positive for fungal infections with 4.68% skin infection cases, 2.34% onychomycosis cases and 1.04% candidiasis cases. Scrapings from onychomycosis and candidiasis patients showed the presence of Aversicolor and Calbicans respectively, resembling exactly the strains isolated from the lake water. However, the skin infection was because of a dermatophyte not isolated for the lake water. Higher prevalence of infection (6.77%) was seen in people using lake water followed by a positive prevalence of 1.30% using tap water. The results of present study suggest that the lake inhabitants are at a greater risk of getting life threatening fungal diseases which may lead to various morbidities. PMID- 26828871 TI - Samples and techniques highlighting the links between obesity and microbiota. AB - The composition of gut microbiota and its relationship to human health, particularly its links with obesity remain an ongoing challenge for scientists. The current gold standard for exploring human gut microbiota consists of using stool samples and only applying next generations sequencing techniques, which sometimes generate contradictory results. Here, we comprehensively describe nutrient absorption, fat digestion, carbohydrate and protein absorption, demonstrating that absorption of these diverse nutrients occurs mainly in the stomach and small intestine. Indeed, bariatric surgery, including Roux-en-Y, removes part of the upper intestine, resulting in weight loss, while colonic surgery is associated with a stable weight. However, most studies only use stool samples rather than small intestine samples because of the easy with which this can be accessed. Metagenomics studies are associated with several biases such as extraction and primer biases and depth bias, including the more modern platforms. High-throughput culture-dependent techniques, such as culturomics, which uses rapid identification methods such as MALDI-TOF, remain time-consuming, but have demonstrated their complementarity with molecular techniques. In conclusion, we believe that a comprehensive analysis of the relationships between obesity and gut microbiota requires large-scale studies coupling metagenomics and culture dependent research, in order to analyse both small intestine and stool samples. PMID- 26828872 TI - Activation of ERK1/2 and TNF-alpha production are regulated by calcium/calmodulin signaling pathway during Penicillium marneffei infection within human macrophages. AB - Previous study have shown that Penicillium marneffei (P. marneffei)-induced TNF alpha production via an extracellular signal-regulated kinase (ERK) mitogen activated protein kinase-dependent mechanism is an important host defence mechanism against P. marneffei in human macrophages. Therefore, we explore signaling pathway that regulates TNF-alpha secretion and activation of ERK1/2 by intracellular signaling mechanisms during P. marneffei infection. We found that ERK1/2 activation was dependent on the calcium/calmodulin/calmodulin kinase II pathway in P. marneffei-infected human macrophages. In contrast, P. marneffei induced p38 MAPK activation was negatively regulated by calcium/calmodulin/calmodulin kinase II signaling pathway. Furthermore, TNF-alpha production in P. marneffei-infected human macrophages was also dependent on Ca(2+)/calmodulin/calmodulin kinase II pathway. These data suggest that Ca(2+)/calmodulin/calmodulin kinase II pathway plays vital regulatory roles in macrophage activation and subsequent cytokine production during P. marneffei infection. PMID- 26828873 TI - The beta3 Adrenergic Receptor Agonist BRL37344 Exacerbates Atrial Structural Remodeling Through iNOS Uncoupling in Canine Models of Atrial Fibrillation. AB - BACKGROUND/AIMS: The role of the beta3-adrenergic receptor (beta3-AR) agonist BRL37344 in atrial fibrillation (AF) structural remodeling and the underlying mechanisms as a therapeutic target were investigated. METHODS: Four groups of dogs were evaluated: sham, pacing, beta3-AR agonist BRL37344 (beta3-AGO), and beta3-AR antagonist L748337 (beta3-ANT) groups. Dogs in the pacing, beta3-AGO and beta3-ANT groups were subjected to rapid atrial pacing for four weeks. Atrial structure and function, AF inducibility and duration, atrial myocyte apoptosis and interstitial fibrosis were assessed. Atrial superoxide anions were evaluated by fluorescence microscopy and colorimetric assays. Cardiac nitrate+nitrite levels were used to assess nitric oxide (NO) production. Protein and mRNA expression of beta3-AR, neuronal NO synthase (nNOS), inducible NO synthase (iNOS), endothelial NO synthase (eNOS) and guanosine triphosphate cyclohydrolase 1 (GCH-1) as well as tetrahydrobiopterin (BH4) levels were measured. RESULTS: beta3-AR was up-regulated in AF. Stimulation of beta3-AR significantly increased atrial myocyte apoptosis, fibrosis and atrial dilatation, resulting in increased AF induction and prolonged duration. These effects were attenuated by beta3-ANT. Moreover, beta3-AGO reduced BH4 and NO production and increased superoxide production, which was inhibited by the specific iNOS inhibitor, 1400w beta3-AGO also increased iNOS but decreased eNOS and had no effect on nNOS expression in AF. CONCLUSIONS: beta3-AR stimulation resulted in atrial structural remodeling by increasing iNOS uncoupling and related oxidative stress. beta3-AR up-regulation and iNOS uncoupling might be underlying AF therapeutic targets. PMID- 26828874 TI - Recent advances in testing of microsphere drug delivery systems. AB - INTRODUCTION: This review discusses advances in the field of microsphere testing. AREAS COVERED: In vitro release-testing methods such as sample and separate, dialysis membrane sacs and USP apparatus IV have been used for microspheres. Based on comparisons of these methods, USP apparatus IV is currently the method of choice. Accelerated in vitro release tests have been developed to shorten the testing time for quality control purposes. In vitro-in vivo correlations using real-time and accelerated release data have been developed, to minimize the need to conduct in vivo performance evaluation. Storage stability studies have been conducted to investigate the influence of various environmental factors on microsphere quality throughout the product shelf life. New tests such as the floating test and the in vitro wash-off test have been developed along with advancement in characterization techniques for other physico-chemical parameters such as particle size, drug content, and thermal properties. EXPERT OPINION: Although significant developments have been made in microsphere release testing, there is still a lack of guidance in this area. Microsphere storage stability studies should be extended to include microspheres containing large molecules. An agreement needs to be reached on the use of particle sizing techniques to avoid inconsistent data. An approach needs to be developed to determine total moisture content of microspheres. PMID- 26828875 TI - A new anthraquinone glycoside from Rhamnus nakaharai and anti-tyrosinase effect of 6-methoxysorigenin. AB - In continual study on the heartwood of Rhamnus nakaharai, a new alaternin-8-O glucoside, namely 1,2,6,8-tetrahydroxy-3-methylanthraquinone-8-O-beta glucopyranoside (1), together with some known compounds were further isolated and characterised by 1-D, 2-D NMR and other spectral evidences. The free radical scavenging and antityrosinase activities of the isolates, including alaternin (1a), emodin (2a), emodin-8-O-beta-glucopyranoside (2), 6-methoxysorigenin-8-O beta-glucopyranoside (3) and 6-methoxysorigenin (3a) were tested. Alaternin (1a) exhibited to be mild DPPH radical scavenger with half as potent as vitamin C, while both alaternin (1a) and emodin-8-O-beta-glucopyranoside (2) exhibited stronger SOD-like activity than that of BHA. 6-Methoxysorigenin (3a), a reported potential antioxidant, and its 8-O-glucoside (3) both performed significant inhibitory effect on mushroom tyrosinase with about twice as potent as kojic acid, the positive control. PMID- 26828876 TI - Prevalence of Primary HIV Drug Resistance in Thailand Detected by Short Reverse Transcriptase Genotypic Resistance Assay. AB - BACKGROUND: HIV drug resistance (HIVDR) is the major cause of treatment failure after scaling up of antiretroviral therapy (ART). HIVDR testing prior to ART initiation is not routinely performed in resource-limited settings. We aimed to assess the prevalence of primary HIVDR by short reverse transcriptase (RT) genotypic resistance assay and evaluate of the impact of the mutations on the treatment outcomes. METHODS: A prospective cohort study was conducted in treatment-naive HIV-infected patients. Fourteen major mutations of codon 99-191 on the RT gene were selected (K103N, V106A/M, V108I, Q151M, Y181C/I, M184V/I, Y188C/L/H, and G190S/A) at a cost of testing of 35 USD. The association between the presence of primary HIVDR and undetectable HIV RNA (<50 copies/mL) after 6 months of ART was determined. RESULTS: A total of 265 HIV-infected patients were included, with a median age of 35.2 (range, 16.8-75.2) years; 62.6% were males. The median (interquartile range) CD4 cell count at ART initiation was 216 (77 381) cells/mm3. The overall prevalence of primary HIVDR was 7.9%. The prevalence of each HIVDR mutation were K103N 6.0%, V106I 1.1%, V108I 0.4%, Y181C 2.3%, Y181I 0.7%, Y181V 0.4%, M184V 3.0%, M184I 1.5%, and G190A 2.3%. No associated factor of having primary HIVDR was determined. By multiple stepwise logistic regression, factors associated with undetectable HIV RNA after 6 months of ART were: having M184V/I (odds ratio [OR] 0.11; 95% confidence interval [CI] 0.02-0.62, p = 0.013), condom use (OR 2.38; 95% CI 1.12-5.06, p = 0.024), and adherence per 5% increase (OR 1.16; 95% CI 1.00-1.35, p = 0.044). CONCLUSIONS: The prevalence of primary HIVDR is approximately 8%; it is associated with detectable HIV RNA at 6 months after ART initiation. Routine "short RT" genotypic resistance assay should be considered in resource-limited settings to maximize treatment outcome. PMID- 26828877 TI - Control of ammonia and urea emissions from urea manufacturing facilities of Petrochemical Industries Company (PIC), Kuwait. AB - Petrochemical Industries Company (PIC) in Kuwait has mitigated the pollution problem of ammonia and urea dust by replacing the melting and prilling units of finished-product urea prills with an environmentally friendly granulation process. PIC has financed a research project conducted by the Coastal and Air Pollution Program's research staff at the Kuwait Institute for Scientific Research to assess the impact of pollution control strategies implemented to maintain a healthy productive environment in and around the manufacturing premises. The project was completed in three phases: the first phase included the pollution monitoring of the melting and prilling units in full operation, the second phase covered the complete shutdown period where production was halted completely and granulation units were installed, and the last phase encompassed the current modified status with granulation units in full operation. There was substantial decrease in ammonia emissions, about 72%, and a 52.7% decrease in urea emissions with the present upgrading of old melting and prilling units to a state-of-the-art technology "granulation process" for a final finished product. The other pollutants, sulfur dioxide (SO2), nitrogen oxides (NOx), and volatile organic compounds (VOCs), have not shown any significant change, as the present modification has not affected the sources of these pollutants. IMPLICATIONS: Petrochemical Industries Company (PIC) in Kuwait has ammonia urea industries, and there were complaints about ammonia and urea dust pollution. PIC has resolved this problem by replacing "melting and prilling unit" of final product urea prills by more environmentally friendly "granulation unit." Environmental Pollution and Climate Program has been assigned the duty of assessing the outcome of this change and how that influenced ammonia and urea dust emissions from the urea manufacturing plant. PMID- 26828878 TI - Introduction: Endoscopic spine surgery. PMID- 26828879 TI - Early experience with endoscopic revision of lumbar spinal fusions. AB - Approximately half a million spinal fusion procedures are performed annually in the US. It is estimated that up to one-third of arthrodesis constructs require revision surgeries. In this study the authors present endoscopic treatment strategies targeting 3 types of complications following arthrodesis surgery: 1) adjacent-level foraminal stenosis; 2) foraminal stenosis at an arthrodesis segment; and 3) stenosis caused by a displaced interbody cage. A retrospective chart review of 11 patients with a mean age of 68 +/- 15 years was performed (continuous variables are shown as the mean +/- SEM). All patients had a history of lumbar arthrodesis surgery and suffered from unilateral radiculopathy. Endoscopic revision surgeries were done as outpatient procedures, and there were no intraoperative or perioperative complications. The cohort included 3 patients with foraminal stenosis at the level of previous arthrodesis. They presented with unilateral radicular leg pain (visual analog scale [VAS] score: 7.3 +/- 2.1) and were severely disabled, as evidenced by an Oswestry Disability Index (ODI) of 46 +/- 4.9. Transforaminal endoscopic foraminotomies were performed, and at a mean follow-up time of 9.0 +/- 2.5 months VAS was reduced by an average of 6.3. The cohort also includes 7 patients suffering unilateral radiculopathy due to adjacent-level foraminal stenosis. Preoperative VAS for leg pain of the symptomatic side was 6.0 +/- 1.6, VAS for back pain was 5.2 +/- 1.7, and ODI was 40 +/- 6.33. Endoscopic decompression led to reduction of the ipsilateral leg VAS score by an average of 5, resulting in leg pain of 1 +/- 0.5 at an average of 8 months of follow-up. The severity of back pain remained stable (VAS 4.2 +/- 1.4). Two of these patients required revision surgery for recurrent symptoms. Finally, this study includes 1 patient who presented with weakness and pain due to retropulsion of an L5/S1 interbody spacer. The patient underwent an endoscopic interlaminar approach with partial resection of the interbody cage, which resulted in complete resolution of her radicular symptoms. Endoscopic surgery may be a useful adjunct for management of certain arthrodesis-related complications. Endoscopic foraminal decompression of previously fused segments and resection of displaced interbody cages appears to have excellent outcomes, whereas decompression of adjacent segments remains challenging and requires further investigation. PMID- 26828881 TI - The anatomic rationale for transforaminal endoscopic interbody fusion: a cadaveric analysis. AB - OBJECTIVE The authors describe a cadaveric analysis to determine the ideal dimensions and trajectory for considering endoscopic transforaminal interbody implantation. METHODS The soft tissues of 8 human cadavers were removed from L-1 to the sacrum, exposing the posterior bony elements. Facetectomies were performed bilaterally at each lumbar level with resection of the pars interarticularis, revealing the pedicles, nerve roots, and interbody disc space. Each level was digitally photographed with a marker for scale and evaluated with digital analysis software. The traversing and exiting nerve roots and pedicle margins were identified, and the distances between these structures and their relationships to the surrounding structures were documented. RESULTS The dimensions of 2 areas were measured: the working triangle and safe zone. The working triangle is the triangle between the exiting and traversing nerve roots above the superior margin of the inferior pedicle. The safe zone is the trapezoid bounded by the widths of the superior and inferior pedicles between the exiting and traversing nerve roots. The mean surface area for the working triangle was 1.83 cm(2), with L5-S1 having the largest area at 2.19 cm(2). The mean surface area of the safe zone was 1.19 cm(2), with L5-S1 having the largest area at 1.26 cm(2). At the medial border of the pedicle extending superiorly, there were no nerve structures within 1.19 cm at any level. On the lateral border of the pedicle, the exiting nerve root was closer superiorly, with the closest being 0.3 cm. CONCLUSIONS The working triangle is a relatively large area. The safe zone, just superior to the pedicle, is free of nerve structures. By utilizing the superior border of the pedicle, the disc space can be accessed within this safe zone without risk of injury to the nerves. A thorough understanding of foraminal anatomy is fundamental for considering how to safely access the disc space, thereby utilizing less invasive endoscopic techniques, and is an important first step in considering what shapes and sizes of interbody implants and retractors are feasible for use in the foramen. PMID- 26828880 TI - The endoscopic transoral approach to the craniovertebral junction: an anatomical study with a clinical example. AB - OBJECTIVE The microscopic transoral, endoscopic transnasal, and endoscopic transoral approaches are used alone and in combination for a variety of craniovertebral junction (CVJ) pathologies. The endoscopic transoral approach provides a more direct exposure that is not restricted by the nasal cavity, pterygoid plates, and palate while sparing the potential morbidities associated with extensive soft-tissue dissection, palatal splitting, or mandibulotomy. Concerns regarding the extent of visualization afforded by the endoscopic transoral approach may be limiting its widespread adoption. METHODS A dissection of 10 cadaver heads was undertaken. CT-based imaging guidance was used to measure the working corridor of the endoscopic transoral approach. Measurements were made relative to the palatal line. The built-in linear measurement tool was used to measure the superior and inferior extents of view. The superolateral extent was measured relative to the midline, as defined by the nasal process of the maxilla. The height of the clivus, odontoid tip, and superior aspect of the C-1 arch were also measured relative to the palatal line. A correlated clinical case is presented with video. RESULTS The CVJ was accessible in all cases. The superior extent of the approach was a mean 19.08 mm above the palatal line (range 11.1 27.7 mm). The superolateral extent relative to the midline was 15.45 mm on the right side (range 9.6-23.7 mm) and 16.70 mm on the left side (range 8.1-26.7 mm). The inferior extent was a mean 34.58 mm below the palatal line (range 22.2-41.6 mm). The mean distances were as follows: palatal line relative to the odontoid tip, 0.97 mm (range -4.9 to 3.7 mm); palatal line relative to the height of the clivus, 4.88 mm (range -1.5 to 7.3 mm); and palatal line relative to the C-1 arch, -2.75 mm (range -5.8 to 0 mm). CONCLUSIONS The endoscopic transoral approach can reliably access the CVJ. This approach avoids the dissections and morbidities associated with a palate-splitting technique (velopharyngeal insufficiency) and the expanded endonasal approach (mucus crusting, sinusitis, and potential lacerum or cavernous-paraclival internal carotid artery injury). For appropriately selected lesions near the palatal line, the endoscopic transoral approach appears to be the preferred approach. PMID- 26828882 TI - Endoscopic minimally invasive transforaminal interbody fusion without general anesthesia: initial clinical experience with 1-year follow-up. AB - OBJECTIVE One of the principal goals of minimally invasive surgery has been to speed postoperative recovery. In this case series, the authors used an endoscopic technique for interbody fusion combined with percutaneous screw fixation to obviate the need for general anesthesia. METHODS The first 10 consecutive patients treated with a minimum of 1 year's follow-up were included in this series. The patients were all treated using endoscopic access through Kambin's triangle to allow for neural decompression, discectomy, endplate preparation, and interbody fusion. This was followed by percutaneous pedicle screw and connecting rod placement using liposomal bupivacaine for long-acting analgesia. No narcotics or regional anesthetics were used during surgery. RESULTS All patients underwent the procedure successfully without conversion to open surgery. The patients' average age was 62.2 +/- 9.0 years (range 52-78 years). All patients had severe disc height collapse, and 60% had a Grade I spondylolisthesis. The mean operative time was 113.5 +/- 6.3 minutes (range 105-120 minutes), and blood loss was 65 +/- 38 ml (range 30-190 ml). The mean length of hospital stay was 1.4 +/- 1.3 nights. There were no intraoperative or postoperative complications. Comparison of preoperative and final clinical metrics demonstrated that the Oswestry Disability Index improved from 42 +/- 11.8 to 13.3 +/- 15.1; the 36-Item Short Form Health Survey (SF-36) Physical Component Summary improved from 47.6 +/- 3.8 to 49.7 +/- 5.4; the SF-36 Mental Component Summary decreased from 47 +/- 3.9 to 46.7 +/- 3.4; and the EQ-5D improved from 10.7 +/- 9.5 to 14.2 +/- 1.6. There were no cases of nonunion identified radiographically on follow-up imaging. CONCLUSIONS Endoscopic fusion under conscious sedation may represent a feasible alternative to traditional lumbar spine fusion in select patients. Larger clinical series are necessary to validate that clinical improvements are sustained and that arthrodesis rates are successful when compared with open surgery. This initial experience demonstrates the possible utility of this procedure. PMID- 26828883 TI - A brief history of endoscopic spine surgery. AB - Few neurosurgeons practicing today have had training in the field of endoscopic spine surgery during residency or fellowship. Nevertheless, over the past 40 years individual spine surgeons from around the world have worked to create a subfield of minimally invasive spine surgery that takes the point of visualization away from the surgeon's eye or the lens of a microscope and puts it directly at the point of spine pathology. What follows is an attempt to describe the story of how endoscopic spine surgery developed and to credit some of those who have been the biggest contributors to its development. PMID- 26828884 TI - Clinical outcomes after percutaneous transforaminal endoscopic discectomy for lumbar disc herniation: a prospective case series. AB - OBJECTIVE Throughout the last decades, full-endoscopic techniques to treat lumbar disc herniation (LDH) have gained popularity in clinical practice. To date, however, no Class I evidence on the efficacy of percutaneous transforaminal endoscopic discectomy (PTED) has been published, and studies describing its safety and short- and long-term efficacy are scarce. In this study the authors aimed to evaluate the clinical outcomes and safety in patients undergoing PTED for LDH. METHODS Patients who underwent PTED for LDH between January 2009 and December 2012 were prospectively followed. The primary outcomes were the visual analog scale (VAS) score for leg pain and the score on the Quebec Back Pain Disability Scale (QBPDS). Secondary outcomes were the perceived experience with the local anesthesia used and satisfaction with the results after 1 year using Likert-type scales. The pretreatment means were compared with the means obtained 6 and 52 weeks after surgery using paired t-tests. RESULTS A total of 166 patients underwent surgery for a total of 167 LDHs. The mean duration of surgery (+/- SD) was 51.0 +/- 9.0 minutes. The 1-year follow-up rate was 95.2%. The mean reported scores on the VAS and QBPDS were 82.5 +/- 17.3 mm and 60.0 +/- 18.4 at baseline, respectively. Six weeks after surgery, the scores on the VAS and QBPDS were significantly reduced to 28.8 +/- 24.5 mm and 26.7 +/- 20.6, respectively (p < 0.001). After 52 weeks of follow-up, the scores were further reduced compared with baseline scores (p < 0.001) to 19.6 +/- 23.5 mm on the VAS and 20.2 +/- 18.1 on the QBPDS. A total of 4 complications were observed, namely 1 dural tear, 1 deficit of ankle dorsiflexion, and 2 cases of transient paresis in the foot due to the use of local anesthetics. CONCLUSIONS PTED appears to be a safe and effective intervention for LDH and has similar clinical outcomes compared to conventional open microdiscectomy. High-quality randomized controlled trials are required to study the efficacy and cost-effectiveness of PTED. PMID- 26828885 TI - Transforaminal endoscopic discectomy to relieve sciatica and delay fusion in a 31 year-old man with pars defects and low-grade spondylolisthesis. AB - Isthmic spondylolisthesis due to pars defects resulting from trauma or spondylolysis is not uncommon. Symptomatic patients with such pars defects are traditionally treated with a variety of fusion surgeries. The authors present a unique case in which such a patient was successfully treated with endoscopic discectomy without iatrogenic destabilization. A 31-year-old man presented with a history of left radicular leg pain along the distribution of the sciatic nerve. He had a disc herniation at L5/S1 and bilateral pars defects with a Grade I spondylolisthesis. Dynamic radiographic studies did not show significant movement of L-5 over S-1. The patient did not desire to have a fusion. After induction of local anesthesia, the patient underwent an awake transforaminal endoscopic discectomy via the extraforaminal approach, with decompression of the L-5 and S-1 nerve roots. His preoperative pain resolved immediately, and he was discharged home the same day. His preoperative Oswestry Disability Index score was 74, and postoperatively it was noted to be 8. At 2-year follow-up he continued to be symptom free, and no radiographic progression of the listhesis was noted. In this case preservation of stabilizing structures, including the supraspinous and interspinous ligaments and the facet capsule, may have reduced the likelihood of iatrogenic instability while at the same time achieving symptom control. This may be a reasonable option for select patient symptoms confined to lumbosacral radiculopathy. PMID- 26828886 TI - Does the microendoscopic technique reduce mortality and major complications in patients undergoing lumbar discectomy? A propensity score-matched analysis using a nationwide administrative database. AB - OBJECTIVE Although minimally invasive spinal surgery has recently gained popularity, few nationwide studies have compared the adverse events that occur during endoscopic versus open spinal surgery. The purpose of this study was to compare perioperative complications associated with microendoscopic discectomy (MED) and open discectomy for patients with lumbar disc herniation. METHODS The authors retrospectively extracted from the Diagnosis Procedure Combination database, a national inpatient database in Japan, data for patients admitted between July 2010 and March 2013. Patients who underwent lumbar discectomy without fusion surgery were included in the analysis, and those with an urgent admission were excluded. The authors examined patient age, sex, Charlson Comorbidity Index, body mass index, smoking status, blood transfusion, duration of anesthesia, type of hospital, and hospital volume (number of patients undergoing discectomy at each hospital). One-to-one propensity score matching between the MED and open discectomy groups was performed to compare the proportions of in-hospital deaths, surgical site infections (SSIs), and major complications, including stroke, acute coronary events, pulmonary embolism, respiratory complications, urinary tract infection, and sepsis. The authors also compared the hospital length of stay between the 2 groups. RESULTS A total of 26,612 patients were identified in the database. The mean age was 49.6 years (SD 17.7 years). Among all patients, 17,406 (65.4%) were male and 6422 (24.1%) underwent MED. A propensity score-matched analysis with 6040 pairs of patients showed significant decreases in the occurrence of major complications (0.8% vs 1.3%, p = 0.01) and SSI (0.1% vs 0.2%, p = 0.02) in patients treated with MED compared with those who underwent open discectomy. Overall, MED was associated with significantly lower risks of major complications (OR 0.62, 95% CI 0.43-0.89, p = 0.01) and SSI (OR 0.29, 95% CI 0.09-0.87, p = 0.03) than open discectomy. There was a significant difference in length of hospital stay (11 vs 15 days, p < 0.001) between the groups. There was no significant difference in in-hospital mortality between MED and open discectomy. CONCLUSIONS The microendoscopic technique was associated with lower risks for SSI and major complications following discectomy in patients with lumbar disc herniation. PMID- 26828887 TI - Early experience with endoscopic foraminotomy in patients with moderate degenerative deformity. AB - OBJECTIVE Asymmetrical degeneration of the disc is one of the most common causes of primary degenerative scoliosis in adults. Coronal deformity is usually less symptomatic than a sagittal deformity because there is less expenditure of energy and hence less effort to maintain upright posture. However, nerve root compression at the fractional curve or at the concave side of the main curve can give rise to debilitating radiculopathy. METHODS This study was a retrospective analysis of 16 patients with coronal deformity of between 10 degrees and 20 degrees . All patients underwent endoscopic foraminal decompression surgery. The pre- and postoperative Cobb angle, visual analog scale (VAS), 36-Item Short Form Health Survey (SF-36), and Oswestry Disability Index scores were measured. RESULTS The average age of the patients was 70.0 +/- 15.5 years (mean +/- SD, range 61-86 years), with a mean followup of 7.5 +/- 5.3 months (range 2-14 months). The average coronal deformity was 16.8 degrees +/- 4.7 degrees (range 10 degrees -41 degrees ). In 8 patients the symptomatic foraminal stenosis was at the level of the fractional curve, and in the remaining patients it was at the concave side of the main curve. One of the patients included in the current cohort had to undergo a repeat operation within 1 week for another disc herniation at the adjacent level. One patient had CSF leakage, which was repaired intraoperatively, and no further complications were noted. On average, preoperative VAS and SF-36 scores showed a tendency for improvement, whereas a dramatic reduction of VAS, by 65% (p = 0.003), was observed in radicular leg pain. CONCLUSIONS Patients with mild to moderate spinal deformity are often compensated and have tolerable levels of back pain. However, unilateral radicular pain resulting from foraminal stenosis can be debilitating. In select cases, an endoscopic discectomy or foraminotomy enables the surgeon to decompress the symptomatic foramen with preservation of essential biomechanical structures, delaying the need for a major deformity correction surgery. PMID- 26828888 TI - Patient radiation exposure during transforaminal lumbar endoscopic spine surgery: a prospective study. AB - OBJECTIVE The aim of this study was to describe patient radiation exposure during single-level transforaminal endoscopic lumbar discectomy procedures at levels L2 5 and L5-S1. METHODS Radiation exposure was monitored in 151 consecutive patients undergoing single-level transforaminal endoscopic lumbar discectomy procedures. Two groups were studied: patients undergoing procedures at the L4-5 level or above and those undergoing an L5-S1 procedure. RESULTS For the discectomy procedures at L4-5 and above, the average duration of fluoroscopy was 38.4 seconds and the mean calculated patient radiation exposure dose was 1.5 mSv. For the L5-S1 procedures, average fluoroscopy time was 54.6 seconds and the mean calculated radiation exposure dose was 2.1 mSv. The average patient radiation exposure dose among these cases represents a 3.5-fold decrease compared with the senior surgeon's first 100 cases. CONCLUSIONS Transforaminal lumbar endoscopic discectomy can be used as a minimally invasive technique for the treatment of lumbar radiculopathy in the setting of a herniated lumbar disc without the significant concern of exposing the patient to harmful doses of radiation. One caveat is that both the surgeon and the patient are likely to be exposed to higher doses of radiation during a surgeon's early experience in minimally invasive endoscopic spine surgery. PMID- 26828889 TI - Transforaminal endoscopic decompression of a postoperative dislocated bone fragment after a 2-level lumbar total disc replacement: case report. AB - The proposed advantages of total disc replacement (TDR) over fusion in the lumbar spine are the preservation of motion and the avoidance of adjacent-level disease. One of the complications inherent in TDR is the possibility of vertebral body fracture due to trauma or a malpositioned implant. The resulting dilemma is that posterior decompression of the displaced bone fragment could then have a destabilizing effect and possibly require fusion, thus obviating the benefit of an arthroplasty procedure. In this study, the authors describe the technical considerations and feasibility of the treatment of a postoperative L-5 paresis that resulted from a dislocated bone fragment at L4-5 during a 2-level lumbar TDR. PMID- 26828890 TI - Technical considerations in transforaminal endoscopic spine surgery at the thoracolumbar junction: report of 3 cases. AB - OBJECTIVE In this study the authors describe the technical considerations and feasibility of transforaminal discectomy and foraminoplasty for the treatment of lumbar radiculopathy in patients who have herniated discs at the thoracolumbar junction. METHODS After institutional review board approval, charts from 3 consecutive patients with lumbar radiculopathy and T12-L1 herniated discs who underwent endoscopic procedures between 2006 and 2014 were reviewed. RESULTS Consecutive cases (n = 1316) were reviewed to determine the incidence and success of surgery performed at the T12-L1 level. Only 3 patients (0.23%) treated with endoscopic surgery for their herniated discs had T12-L1 herniated discs; the rest were lumbar or lumbosacral herniations. For patients with T12-L1 disc herniations, the average preoperative visual analog scale score was 8.3 (indicated in the questionnaire as describing severe and constant pain). The average 1-year postoperative visual analog scale score was 1.7 (indicated in the questionnaire as mild and intermittent pain). CONCLUSIONS Transforaminal endoscopic discectomy and foraminotomy can be used as a safe yet minimally invasive technique for the treatment of lumbar radiculopathy in the setting of a thoracolumbar disc herniation. PMID- 26828891 TI - Who was the Red Dean? PMID- 26828892 TI - Neuroprotective Activity of Curcumin in Combination with Piperine against Quinolinic Acid Induced Neurodegeneration in Rats. AB - AIM: Quinolinic acid (QA) is an excitotoxin that induces Huntington's-like symptoms in animals and humans. Curcumin (CMN) is a well-known antioxidant but the major problem is its bioavailability. Therefore, the present study was designed to investigate the effect of CMN in the presence of piperine against QA induced excitotoxic cell death in rats. MATERIAL AND METHODS: QA was administered intrastriatally at a dose of 200 nmol/2 ul saline, bilaterally. CMN (25 and 50 mg/kg/day, p.o.) and combination of CMN (25 mg/kg/day, p.o.) and with piperine (2.5 mg/kg/day, p.o.) was administered daily for the next 21 days. Body weight and behavioral parameters were observed on 1st, 7th, 14th and 21st day. On the 22nd day, animals were sacrificed and striatum was isolated for biochemical (LPO, nitrite and GSH), neuroinflammatory (interleukin (IL)-1beta, IL-6 and TNF-alpha) and neurochemical (dopamine, norepinephrine, GABA, glutamate, 5-HT, 3,4 dihydroxyphenylacetic acid and homovanillic acid) estimation. RESULTS: CMN treatment showed beneficial effect against QA-induced motor deficit, biochemical and neurochemical abnormalities in rats. Combination of piperine (2.5 mg/kg/day, p.o.) with CMN (25 mg/kg/day, p.o.) significantly enhanced its protective effect as compared to treatment with CMN alone. CONCLUSION: This study has revealed that the combination of CMN and piperine showed strong antioxidant and protective effect against QA-induced behavioral and neurological alteration in rats. PMID- 26828893 TI - Elevated temperatures and long drought periods have a negative impact on survival and fitness of strongylid third stage larvae. AB - In grazing cattle, infections with gastrointestinal nematodes pose some of the most important health threats and subclinical infections result in considerable production losses. While there is little doubt that climate change will affect grazing ruminants directly, mean temperature increases of ~ 3 degrees C and longer drought stress periods in summer may also influence the free-living stages of parasitic nematodes. Hostile climatic conditions reduce the number of L3s on pasture and therefore the refugium, which is expected to result in a higher selection pressure, accelerating development of resistance against anthelmintic drugs. The aim of the current experiments was to investigate the effects of drought stress and different temperature/humidity ranges over time on the survival and fitness of Cooperia oncophora L3s and their distribution in grass and soil under controlled conditions using a climate chamber. Grass containers inoculated with L3s were analysed after 1-6weeks using descriptive statistics as well as linear models. A large proportion of L3s was recovered from soil where fitness was also better preserved than on grass. Numbers and fitness of recovered L3s declined with duration in the climate chamber under both temperature profiles. However, the results of the linear models confirmed that higher temperatures (20-33 degrees C versus 17-22.6 degrees C) significantly impaired survival, distribution and fitness of L3s. Application of drought stress, known as another important factor, had a surprisingly smaller impact than its duration or higher temperatures. The climate chamber enabled exclusion of confounding factors and therefore accurate interpretation of the investigated climatic aspects. The obtained results highlight the relative importance of those factors, and will help to design better models for the population dynamics of L3s on pasture in the future. Additionally, the outcomes of these investigations may offer explanations regarding interdependencies of development of anthelmintic resistance and the presence of hot/dry weather conditions. PMID- 26828894 TI - Avian malaria in a boreal resident species: long-term temporal variability, and increased prevalence in birds with avian keratin disorder. AB - The prevalence of vector-borne parasitic diseases is widely influenced by biological and ecological factors. Environmental conditions such as temperature and precipitation can have a marked effect on haemosporidian parasites (Plasmodium spp.) that cause malaria and those that cause other malaria-like diseases in birds. However, there have been few long-term studies monitoring haemosporidian infections in birds in northern latitudes, where weather conditions can be highly variable and the effects of climate change are becoming more pronounced. We used molecular methods to screen more than 2,000 blood samples collected from black-capped chickadees (Poecile atricapillus), a resident passerine bird. Samples were collected over a 10 year period, mostly during the non-breeding season, at seven sites in Alaska, USA. We tested for associations between Plasmodium prevalence and local environmental conditions including temperature, precipitation, site, year and season. We also evaluated the relationship between parasite prevalence and individual host factors of age, sex and presence or absence of avian keratin disorder. This disease, which causes accelerated keratin growth in the beak, provided a natural study system in which to test the interaction between disease state and malaria prevalence. Prevalence of Plasmodium infection varied by year, site, age and individual disease status but there was no support for an effect of sex or seasonal period. Significantly, birds with avian keratin disorder were 2.6 times more likely to be infected by Plasmodium than birds without the disorder. Interannual variation in the prevalence of Plasmodium infection at different sites was positively correlated with summer temperatures at the local but not statewide scale. Sequence analysis of the parasite cytochrome b gene revealed a single Plasmodium spp. lineage, P43. Our results demonstrate associations between prevalence of avian malaria and a variety of biological and ecological factors. These results also provide important baseline data that will be informative for predicting future changes in Plasmodium prevalence in the subarctic. PMID- 26828895 TI - Triclosan (TCS) exposure impairs lipid metabolism in zebrafish embryos. AB - Triclosan (TCS) is an active antimicrobial ingredient used in many household products, such as skin creams and toothpaste. It is produced in high volumes, and humans are directly exposed to it and dispose it on a daily basis. TCS has been found to contaminate water worldwide. This study aimed to understand the potential developmental and metabolic abnormalities caused by TCS exposure by using zebrafish as the experimental model. Four developmental stages (70-85% epiboly, 10-12 somite, prim-5, and 5dpf) were selected to perform in situ hybridization staining to investigate the effects of TCS on dorsal ventral patterning, segmentation, brain development, and organ formation. Results showed, in terms of developmental toxicology, that neither phenotypic nor molecular changes were found after 5 days of 250MUg/L TCS exposure. However, such dosage of TCS exposure resulted in lipid droplet accumulation in the yolk sac, which might due to the deregulated mRNA expression level of beta-oxidation transcripts. This study showed that 250MUg/L TCS exposure does not affect normal embryogenesis or organogenesis; however, there are concerns regarding possible impairment of lipid metabolism. PMID- 26828896 TI - Colorectal cancer survival by stage of cases diagnosed in Mallorca, Spain, between 2006 and 2011 and factors associated with survival. AB - OBJECTIVES: To establish cause-specific survival by stage of colorectal cancer up to 8 years from diagnosis, and to identify factors which explain and predict the likelihood of survival. METHODOLOGY: Retrospective follow-up study of people diagnosed with invasive colorectal cancer during 2006-2011, identified through the Mallorca Cancer Registry. DCO and lymphomas were excluded. Sex, age, diagnostic method, site, histology, T, N, M, and stage, date of diagnosis, date of follow-up or death, and cause of death were collected. End point of follow-up was 31st December 2013. Multiple imputation (MI) method was performed to obtain stage when unknown. Actuarial and Kaplan-Meier methods were used for survival analysis. Extended Cox models were built to identify factors that explain and predict survival. RESULTS: 2889 cases were identified, 41.7% in women and 58.3% in men, with a mean age of 70.5 years. Unknown stage represented 15.3% of cases. After MI, 15% were in stage I, 26.7% were in II, 32.7% in III, and 25.6% in IV. Survival was 56% at the end of the 5th year. Survival by stage changed significantly after MI and was estimated to 83% at stage I, 73% at II, 62% at III, and 16% at IV. Extended Cox model showed that survival worsened with age, mucinous histology, and stage. Risk of dying was 17.0 times higher in stage IV compared to stage I, 3.7 times in stage III, and 1.6 times in stage II. CONCLUSIONS: More than half of colorectal cancer patients will survive 5 years after diagnosis, but only if diagnosed in stages I-III. PMID- 26828897 TI - Internalized stigma and quality of life domains among people with mental illness: the mediating role of self-esteem. AB - BACKGROUND: People with mental illness who internalize stigma often experience reduced self-esteem and impaired quality of life (QOL). AIMS: To propose a theoretical model in which self-esteem mediates the effects of internalized stigma on the multidimensional domains comprising QOL. METHOD: In 403 inpatients and outpatients (DSM-IV, American Psychiatric Association, 1994), from hospital based and community mental health facilities, self-report measures of internalized stigma (ISMI), self-esteem (RSES) and QOL (WHOQOL-Bref) were administrated. RESULTS: Structural equation modeling results supported the proposed model. Self-esteem fully mediated the relation between internalized stigma and the physical and the social relationships domains, and partially mediated the relationship between internalized stigma and psychological, environment and level of independence QOL domains. Such results provided empirical support and shed light upon previous research. Specifically the results emphasize the mediating role that self-esteem plays in the degree to which internalized stigma exerts a negative effect on specific QOL domains. CONCLUSIONS: Self-esteem appears to be a core element in reducing the negative effects of internalized stigma on aspects of QOL among people with mental illness. These findings suggest there is a crucial impact regarding clinical mental health interventions along with important theoretical implications. PMID- 26828898 TI - Between ideals and reality in home-based rehabilitation. AB - SETTING AND OBJECTIVE: The growing elderly population and the rising number of people with chronic diseases indicate an increasing need for rehabilitation. Norwegian municipalities are required by law to offer rehabilitation. The aim of this study was to investigate how rehabilitation work is perceived and carried out by first-line service providers compared with the guidelines issued by Norway's health authorities. DESIGN AND SUBJECTS: In this action research project, qualitative data were collected through 24 individual interviews and seven group interviews with employees--service providers and managers--in the home-based service of two boroughs in Oslo, Norway. The data were analysed using a systematic text-condensation method. RESULTS: The results show that rehabilitation receives little attention in the boroughs and that patients are seldom rehabilitated at home. There is disagreement among professional staff as to what rehabilitation is and should be. The purchaser-provider organization, high speed of service delivery, and scarcity of resources are reported to hamper rehabilitation work. CONCLUSION AND IMPLICATIONS: A discrepancy exists between the high level of ambitious goals of Norwegian health authorities and the possibilities that practitioners have to achieve them. This situation results in healthcare staff being squeezed by the increasing expectations and demands of the population and the promises and statutory rights coming from politicians and administrators. For the employees in the municipalities to place rehabilitation on the agenda, it is a requirement that authorities understand the clinical aspect of rehabilitation and provide the municipalities with adequate framework conditions for successful rehabilitation work. KEY POINTS: Home-based rehabilitation is documented to be effective, and access to rehabilitation has been established in Norwegian law. The purchaser-provider organization, high rate of speed, and a scarcity of resources in home-based services hamper rehabilitation work. Healthcare providers find themselves squeezed between the health authorities' overarching guidelines and requirements and the possibilities of achieving them. Rehabilitation must be placed on the agenda on the condition that authorities understand the clinical aspect of rehabilitation. PMID- 26828899 TI - Strengthening Agronomy Research for Food Security and Environmental Quality. PMID- 26828900 TI - A novel bispecific antibody, BiSS, with potent anti-cancer activities. AB - One of the most active fields in cancer immunotherapy is the study of bispecific antibodies, which engage immune cells to kill cancer cells. However, a variety of issues are associated with most of current bispecific antibody formats. In this study, we present a novel bispecific antibody, BiSS (Bispecific antibody with Single domain, Single domain antibodies), which was constructed by linking 2 single domain antibodies, anti-CEA and anti-CD16, in tandem. Unlike most other bispecific antibodies, the BiSS antibody can be expressed and purified from E.coli in large quantities. By recruiting natural killer cells (NK cells) to CEA positive cancer cells, BiSS led to cancer cell death in vitro. In xenograft models, the BiSS protein blocked cancer progression. The data suggested that the single domain-based bispecific antibody BiSS was functional and can be potentially applied to a broad range of immunotherapies. PMID- 26828901 TI - Income and Subjective Well-Being: New Insights from Relatively Healthy American Women, Ages 49-79. AB - The interests of economists, psychologists, social scientists and others on the relations of income, demographics, religion and subjective well-being, have generated a vast global literature. It is apparent that biomedical research has focused on white with men. The Women's Health Initiative and Observational Study (WHI OS) was initiated in 1992. The OS represents the scientific need for social priorities to improve the health and welfare of women; it includes 93.676 relatively healthy postmenopausal women, 49 to 79, from diverse backgrounds. The objective of this study is to examine how lifestyle and other factors influence women's health. Data from the WHI OS questionnaire were analyzed. Statistical methods included descriptive statistics square, correlations, linear regression and analyses of covariance (GLM). New findings and insights relate primarily to general health, religion, club attendance, and likelihood of depression. The most important predictor of excellent or very good health is quality of life and general health is a major predictor of quality of life. A great deal of strength and comfort from religion was reported by 62.98% of the women, with little variation by denomination. More from religion related to poorer health, and less likelihood of depression. Religion and lower income are in accord with of across country studies. Attendance at clubs was associated with religion and with all factors associated with religion, except income. Though general health and likelihood of depression are highly correlated, better health is associated with higher income; however, likelihood of depression is not associated with income- contrary to conventional wisdom about socioeconomic disparities and mental health. Subjective well-being variables, with the exception of quality of life, were not associated with income. Social networks--religion and clubs--among a diverse population, warrant further attention from economists, psychologists, sociologists, and others. PMID- 26828902 TI - AC Electric Field Enhances Cryopreservation Efficiency of Sprague-Dawley Rat Liver During a Slow Freezing Procedure. AB - Slow freezing coupled with an AC electric field (ACEF) has been demonstrated to miniaturize the ice crystals of a 0.9% (w/v) NaCl solution in a prior study. The aim of this study was to assess the effect of ACEF on Sprague-Dawley (SD) rat liver in vitro during the slow cooling procedure. SD rat liver exposed to an oscillating electric field was frozen in a programmed freezer initially down to 30 degrees C at a cooling rate of -1 degrees C/min and continuing down to -80 degrees C at a cooling rate of -5 degrees C/min. The cryovials were finally transferred into liquid nitrogen for 7 days. The frequency range was 0-20 MHz, and peak field strength was 1,000 V/m. For the sham and electric-exposed groups, the freezing solution consisted of 0%, 2.5%, 5.0%, 7.5%, or 10% (v/v) dimethyl sulfoxide (DMSO) Dulbecco's modified Eagles' medium culture solution, and fresh tissue was selected as the control group. The changes in cell survival rate, adenosine triphosphate (ATP) content, and morphology of fresh and frozen-thawed liver tissue were examined. Compared with the sham group with 5.0% DMSO, the result showed that slow freezing coupled with 2.45 MHz or 5 MHz ACEF significantly increased the relative survival rate by 43.27% and 26.31% (P < 0.001), respectively. However, ACEF exposure increased the ATP content compared with the sham group. Especially in 5% and 10% DMSO with 2.45 MHz ACEF exposure, the ATP content approximated the fresh group (7.3 +/- 2.7 nmol/piece), corresponding to 94.52% and 80.82%. In addition, the cellular membrane and some organelles (e.g., mitochondria) in the electric-exposed group appeared to be more intact according to the transmission electron microscopy images. The underlying mechanism might be that the ACEF affects the formation and growth of the ice crystallization, and thus inhibits cryoinjury. These results show that ACEF would provide an efficient method for cryopreservation banking with a low concentration of CPA during the slow freezing process. PMID- 26828903 TI - Revealing the challenges of low template DNA analysis with the prototype Ion AmpliSeqTM Identity panel v2.3 on the PGMTM Sequencer. AB - Forensic scientists frequently have to deal with the analysis of challenging sources of DNA such as degraded and low template DNA (LtDNA). The capacity to genotype difficult biological traces has been facilitated by emerging technologies. Massive parallel sequencing (MPS) on microchip among other technologies promises high sensitivity and discrimination power. In this study we evaluated the combined use of the Quantifiler((r)) Trio DNA Quantification Kit with the prototype Ion AmpliSeqTM Identity panel v2.3 and PGMTM platform in LtDNA samples. Coverage, allele balance, allele drop-out/in, consistency and variance were assessed. Overall, the results showed a great level of performance and consistency in terms of genotyping capability even under the most challenging conditions, making it possible to obtain consistent SNP profiles with 31 pg of DNA and partial informative profiles with as little as 5 pg or with severely degraded DNA. In addition, we demonstrated that the stochastic effects observed in some samples are due to the amplification of the library rather than sequencing. Based on our data, we proposed general recommendations for the analysis of casework samples starting from the use of quantification data, which proved to be critical in deciding whether to process the samples via STR (short tandem repeat) analysis or SNP MPS. In our experience, the use of the prototype Ion AmpliSeqTM Identity panel v2.3 has revealed a new applicable solution for processing LtDNAs. This approach provides users with an additional tool for analysis of traces that either would not give informative results with conventional STR-based techniques. PMID- 26828904 TI - A Whole-Cell Surface Plasmon Resonance Sensor Based on a Leucine Auxotroph of Escherichia coli Displaying a Gold-Binding Protein: Usefulness for Diagnosis of Maple Syrup Urine Disease. AB - We developed a whole-cell surface plasmon resonance (SPR) sensor based on a leucine auxotroph of Escherichia coli displaying a gold-binding protein (GBP) in response to cell growth and applied this sensor to the diagnosis of maple syrup urine disease, which is represented by the elevated leucine level in blood. The leucine auxotroph was genetically engineered to grow displaying GBP in a proportion to the concentration of target amino acid leucine. The GBP expressed on the surface of the auxotrophs directly bound to the golden surface of an SPR chip without the need for any additional treatment or reagents, which consequently produced SPR signals used to determine leucine levels in a test sample. Gold nanoparticles (GNPs) were further applied to the SPR system, which significantly enhanced the signal intensity up to 10-fold by specifically binding to GBP expressed on the cell surface. Finally, the diagnostic utility of our system was demonstrated by its employment in reliably determining different statuses of maple syrup urine disease based on a known cutoff level of leucine. This new approach based on an amino acid-auxotrophic E. coli strain expressing a GBP that binds to an SPR sensor holds great promise for detection of other metabolic diseases of newborn babies including homocystinuria and phenylketonuria, which are also associated with abnormal levels of amino acids. PMID- 26828905 TI - Major clinical response to nivolumab in relapsed/refractory Hodgkin lymphoma after allogeneic stem cell transplantation. PMID- 26828906 TI - Prevalence and determinants of fatigue in patients with moderate to severe chronic GvHD. AB - Although fatigue is common after allogeneic hematopoietic cell transplantation, little is known about fatigue in patients with chronic GvHD (cGvHD). The aim of this study was to explore factors associated with fatigue in cGvHD. Data were drawn from a sequentially recruited, cross-sectional study of adults with moderate or severe cGvHD (n=263). Respondents were classified as fatigued or not fatigued based on their response to a single item regarding loss of energy from the Lee cGvHD Symptom Scale. In univariate analysis, factors significantly associated with fatigue included performance status, number of prior cGvHD therapies, cGvHD symptom bother, self-assessed physical and mental health, nutritional status, walk velocity and self-reported physical activity. There were no significant associations between fatigue and disease-related cGvHD variables. Multivariable logistic regression demonstrated that being less active and having pulmonary and/or muscle/joint symptoms were independently associated with fatigue. In conclusion, clinically significant fatigue was prevalent in more than one-third of subjects with cGvHD, and was disabling. Absence of association with measures of cGvHD severity underscores the need to elucidate the pathogenesis of fatigue and its relationship with inflammatory activity. Pulmonary and muscle/joint symptoms and physical inactivity represent potential targets for intervention in clinical studies. PMID- 26828907 TI - Left ventricular mass and ambulatory blood pressure are increased in long-term survivors of childhood cancer after autologous SCT. PMID- 26828908 TI - Erratum to: MR imaging of perianal fistulas in Crohn's disease: sensitivity and specificity of STIR sequences. PMID- 26828909 TI - Armchair-edged nanoribbon as a bottleneck to electronic total transmission through a topologically nontrivial graphene nanojunction. AB - It is currently a promising approach to experimentally realize the topological insulator phase transition of graphene by introducing the extrinsic spin-orbit coupling (SOC). Then, electronic total transmission through various topological nontrivial graphene nanojunctions (GNJs) is obtainable, if the electronic transport is supported by the helical edge states. Though the bulk graphene is a gapless semiconductor, the inter-valley scattering could introduce a topological trivial gap in semiconducting armchair-edged graphene nanoribbon (GNR). The SOC should be strong enough to reopen a topological nontrivial gap before close such a trivial gap. Therefore, our theoretical study indicates that a semiconducting armchair-edged graphene nanoribbon (GNR) can not develop the helical edge states when the SOC strength is lower than a threshold, though the bulk phase is topological nontrivial. This implies a competition between the SOC and the inter valley scattering. However, for a metallic armchair-edged GNR, a small SOC can always open a nontrivial gap. Nevertheless, the helical edge state is much less localized than that in a zigzag-edged GNR of the same width. As a result, and by numerically calculating the electronic transmission spectrum of step- and L shaped GNJs, we conclude that when an armchair-edged GNR is a part of a GNJ, it is the weak point to realize the electronic total transmission even though the bulk phase of graphene is topologically insulating. PMID- 26828910 TI - Attachment-based family therapy and emotion-focused therapy for unresolved anger: The role of productive emotional processing. AB - A growing body of research suggests that emotional processing is a central and common change mechanism across various types of therapies (Diener & Hilsenroth, 2009; Foa, Huppert, & Cahill, 2006; Greenberg, 2011). This study examined whether 10 weeks of attachment-based family therapy (ABFT), characterized by the use of in-session young adult-parent dialogues, were more effective than 10 weeks of individual emotion-focused therapy (EFT), characterized by the use of imaginal dialogues, in terms of facilitating productive emotional processing among a sample of 32 young adults presenting with unresolved anger toward a parent. This study also examined whether greater amounts of productive emotional processing predicted more favorable treatment outcomes. In contrast to our expectations, we found significantly more productive emotional processing in individual EFT than in conjoint ABFT. Results also showed that while both treatments led to significant and equivalent decreases in unresolved anger, state anger, attachment anxiety, and psychological symptoms, only ABFT was associated with decreases in attachment avoidance. Although amount of emotional processing did not explain the unique decrease in attachment avoidance in ABFT, greater amounts of productive emotional processing predicted greater decreases in psychological symptoms (but not other outcome measures) across both treatments. PMID- 26828912 TI - Coping Strategies and Associations With Depression Among 12- to 15-Year-Old Norwegian Adolescents Involved in Bullying. AB - The aim of this study was to examine coping styles among young adolescents involved in bullying, both as victims or aggressors, and the relationships between coping styles and depressive symptom levels. The possible moderating and mediating roles of coping in the relationships between bullying involvement and depression are also investigated. A representative community sample of 2464 adolescents was assessed. Coping styles were measured by the Coping Inventory for Stressful Situations. Depressive symptoms were assessed by the Mood and Feelings Questionnaire. Analysis of variance and standard linear regression methods were applied. Adolescents being bullied or being aggressive toward others both showed more emotional coping than did noninvolved adolescents (p < 0.001). Being bullied and high emotional, low task, and high avoidant coping styles were independently related to more depressive symptoms. The association between being bullied and depressive symptoms was both moderated and partially mediated by emotional coping. PMID- 26828911 TI - Perspectives on the Use of eHealth in the Management of Patients With Schizophrenia. AB - Mobile devices, digital technologies, and web-based applications-known collectively as eHealth (electronic health)-could improve health care delivery for costly, chronic diseases such as schizophrenia. Pharmacologic and psychosocial therapies represent the primary treatment for individuals with schizophrenia; however, extensive resources are required to support adherence, facilitate continuity of care, and prevent relapse and its sequelae. This paper addresses the use of eHealth in the management of schizophrenia based on a roundtable discussion with a panel of experts, which included psychiatrists, a medical technology innovator, a mental health advocate, a family caregiver, a health policy maker, and a third-party payor. The expert panel discussed the uses, benefits, and limitations of emerging eHealth with the capability to integrate care and extend service accessibility, monitor patient status in real time, enhance medication adherence, and empower patients to take a more active role in managing their disease. In summary, to support this technological future, eHealth requires significant research regarding implementation, patient barriers, policy, and funding. PMID- 26828913 TI - Risk Factors for Posttraumatic Stress Symptoms Among Avalanche Survivors: A 16 Year Follow-Up. AB - Few natural disaster studies have assessed factors associated with posttraumatic stress disorder (PTSD) beyond a decade after trauma. Using North's disaster model as a framework, the aim of this study was to identify factors associated with clinically significant posttraumatic stress symptoms (CS-PTSDS) in avalanche survivors (n = 399) 16 years after the disaster. Completed self-report questionnaires were received from 286 (72%) survivors. CS-PTSDS were assessed with the Posttraumatic Diagnostic Scale. Predictors of CS-PTSDS in a multivariate analysis were secondary sequelae factors of lack of social support (adjusted relative risk [RR], 2.90; 95% confidence interval [CI], 1.37-6.13) and financial hardship in the aftermath of the trauma (adjusted RR, 2.47; 95% CI, 1.16-5.26). In addition, the community factor of providing assistance in the aftermath of the avalanche (adjusted RR, 1.95; 95% CI, 1.04-3.64) was inversely associated with CS PTSDS. Screening for these factors may be useful in identifying those most vulnerable to developing chronic PTSD after this unique type of disaster. PMID- 26828918 TI - Gut microbiota in 2015: Prevotella in the gut: choose carefully. AB - Gut microbial communities often contain many Bacteroides or their close relatives, Prevotella, but not both. Prevotella strains are associated with plant rich diets but are also linked with chronic inflammatory conditions. In 2015, papers probed the genomic diversity of Prevotella strains and interactions of Prevotella copri with its host and other bacteria. PMID- 26828919 TI - Are Clinicians Better Than Lay Judges at Recalling Case Details? An Evaluation of Expert Memory. AB - OBJECTIVE: This study examined the role of expertise in clinicians' memory for case details. Clinicians' diagnostic formulations may afford mechanisms for retaining and retrieving information. METHOD: Experts (N = 41; 47.6% males, 23.8% females; 28.6% did not report gender; age: mean [M] = 54.69) were members of the American Board of Professional Psychologists. Lay judges (N = 156; 25.4% males, 74.1% females; age: M = 18.85) were undergraduates enrolled in general psychology. Three vignettes were presented to each group, creating a 2 (group: expert, lay judge) x 3 (vignettes: simple, complex-coherent, complex-incoherent) mixed factorial design. Recall accuracy for vignette details was the dependent variable. RESULTS: Data analyses used multivariate analyses of variance to detect group differences among multiple continuous variables. Experts recalled more information than lay judges, overall. However, experts also exhibited more false memories for the complex-incoherent case because of their schema-based knowledge. CONCLUSIONS: This study supported clinical expertise as beneficial. Nonetheless, negative influences from experts' schema-based knowledge, as exhibited, could adversely affect clinical practices. PMID- 26828920 TI - Highly Tm(3+) doped germanate glass and its single mode fiber for 2.0 MUm laser. AB - Highly Tm(3+) doped optical fibers are urgently desirable for 2.0 MUm compact single-frequency fiber laser and high-repetition-rate mode-locked fiber laser. Here, we systematically investigated the optical parameters, energy transfer processes and thermal properties of Tm(3+) doped barium gallo-germanate (BGG) glasses. Highly Tm(3+) doped BGG glass single mode (SM) fibers were fabricated by the rod-in-tube technique. The Tm(3+) doping concentration reaches 7.6 * 10(20) ions/cm(3), being the reported highest level in Tm(3+) doped BGG SM fibers. Using ultra short (1.6 cm) as-drawn highly Tm(3+) doped BGG SM fiber, a single frequency fiber laser at 1.95 MUm has been demonstrated with a maximum output power of 35 mW when in-band pumped by a home-made 1568 nm fiber laser. Additionally, a multilongitudinal-mode fiber laser at 1.95 MUm has also been achieved in a 10 cm long as-drawn active fiber, yielding a maximum laser output power of 165 mW and a slope efficiency of 17%. The results confirm that the as drawn highly Tm(3+) doped BGG SM fibers are promising in applications that require high gain and high power from a short piece of active optical fiber. PMID- 26828921 TI - Cognitive Enhancement to Improve Substance Abuse Outcomes in Persons With Co Occurring Disorders. PMID- 26828922 TI - Keeping Pace with Your Eating: Visual Feedback Affects Eating Rate in Humans. AB - Deliberately eating at a slower pace promotes satiation and eating quickly has been associated with a higher body mass index. Therefore, understanding factors that affect eating rate should be given high priority. Eating rate is affected by the physical/textural properties of a food, by motivational state, and by portion size and palatability. This study explored the prospect that eating rate is also influenced by a hitherto unexplored cognitive process that uses ongoing perceptual estimates of the volume of food remaining in a container to adjust intake during a meal. A 2 (amount seen; 300 ml or 500 ml) x 2 (amount eaten; 300 ml or 500 ml) between-subjects design was employed (10 participants in each condition). In two 'congruent' conditions, the same amount was seen at the outset and then subsequently consumed (300 ml or 500 ml). To dissociate visual feedback of portion size and actual amount consumed, food was covertly added or removed from a bowl using a peristaltic pump. This created two additional 'incongruent' conditions, in which 300 ml was seen but 500 ml was eaten or vice versa. We repeated these conditions using a savoury soup and a sweet dessert. Eating rate (ml per second) was assessed during lunch. After lunch we assessed fullness over a 60-minute period. In the congruent conditions, eating rate was unaffected by the actual volume of food that was consumed (300 ml or 500 ml). By contrast, we observed a marked difference across the incongruent conditions. Specifically, participants who saw 300 ml but actually consumed 500 ml ate at a faster rate than participants who saw 500 ml but actually consumed 300 ml. Participants were unaware that their portion size had been manipulated. Nevertheless, when it disappeared faster or slower than anticipated they adjusted their rate of eating accordingly. This suggests that the control of eating rate involves visual feedback and is not a simple reflexive response to orosensory stimulation. PMID- 26828923 TI - Silodosin, an alpha(1A)-Adrenoceptor Antagonist, May Ameliorate Ischemia-Induced Bladder Denervation and Detrusor Dysfunction by Improving Bladder Blood Flow. AB - BACKGROUND/AIMS: This study was performed to investigate the detailed mechanism underlying the effects of the selective alpha(1A)-adrenoceptor antagonist, silodosin, on bladder function in a rat model of atherosclerosis-induced chronic bladder ischemia (CBI). METHODS: The CBI model was prepared by balloon endothelial injury of the bilateral iliac arteries in male rats. Using an osmotic pump, the CBI rats received either silodosin or vehicle alone subcutaneously for 8 weeks. Rats received a 2% cholesterol diet throughout the experiment. Bladder blood flow (BBF) was measured. Immunohistochemical staining was performed to determine the nerve distribution and nerve growth factor expression in the bladder. Bladders were used for muscle strip contraction analysis. The expression levels of muscarinic M2 and M3 receptors were measured. RESULTS: Silodosin abrogated the decrease in BBF in CBI rats. Silodosin prevented the decrease in nerve distribution and increase in nerve growth factor expression in the CBI model. Bladder contractile response was reduced in the CBI group. Silodosin ameliorated the effect on the bladder contractile response. The level of muscarinic M3 receptor mRNA present in the bladder of CBI rats was increased by silodosin. CONCLUSION: The results of this study suggest that silodosin ameliorates the denervation of the bladder and effects on detrusor contractile function under ischemic conditions by restoring BBF. PMID- 26828924 TI - OGR1/GPR68 Modulates the Severity of Experimental Autoimmune Encephalomyelitis and Regulates Nitric Oxide Production by Macrophages. AB - Ovarian cancer G protein-coupled receptor 1 (OGR1) is a proton-sensing molecule that can detect decreases in extracellular pH that occur during inflammation. Although OGR1 has been shown to have pro-inflammatory functions in various diseases, its role in autoimmunity has not been examined. We therefore sought to determine whether OGR1 has a role in the development of T cell autoimmunity by contrasting the development of experimental autoimmune encephalomyelitis between wild type and OGR1-knockout mice. OGR1-knockout mice showed a drastically attenuated clinical course of disease that was associated with a profound reduction in the expansion of myelin oligodendrocyte glycoprotein 35-55-reactive T helper 1 (Th1) and Th17 cells in the periphery and a reduced accumulation of Th1 and Th17 effectors in the central nervous system. We determined that these impaired T cell responses in OGR1-knockout mice associated with a reduced frequency and number of dendritic cells in draining lymph nodes during EAE and a higher production of nitric oxide by macrophages. Our studies suggest that OGR1 plays a key role in regulating T cell responses during autoimmunity. PMID- 26828925 TI - Weak Epistasis Generally Stabilizes Phenotypes in a Mouse Intercross. AB - The extent and strength of epistasis is commonly unresolved in genetic studies, and observed epistasis is often difficult to interpret in terms of biological consequences or overall genetic architecture. We investigated the prevalence and consequences of epistasis by analyzing four body composition phenotypes--body weight, body fat percentage, femoral density, and femoral circumference--in a large F2 intercross of B6-lit/lit and C3.B6-lit/lit mice. We used Combined Analysis of Pleiotropy and Epistasis (CAPE) to examine interactions for the four phenotypes simultaneously, which revealed an extensive directed network of genetic loci interacting with each other, circulating IGF1, and sex to influence these phenotypes. The majority of epistatic interactions had small effects relative to additive effects of individual loci, and tended to stabilize phenotypes towards the mean of the population rather than extremes. Interactive effects of two alleles inherited from one parental strain commonly resulted in phenotypes closer to the population mean than the additive effects from the two loci, and often much closer to the mean than either single-locus model. Alternatively, combinations of alleles inherited from different parent strains contribute to more extreme phenotypes not observed in either parental strain. This class of phenotype-stabilizing interactions has effects that are close to additive and are thus difficult to detect except in very large intercrosses. Nevertheless, we found these interactions to be useful in generating hypotheses for functional relationships between genetic loci. Our findings suggest that while epistasis is often weak and unlikely to account for a large proportion of heritable variance, even small-effect genetic interactions can facilitate hypotheses of underlying biology in well-powered studies. PMID- 26828926 TI - Spermine inhibits Endoplasmic Reticulum Stress-induced Apoptosis: a New Strategy to Prevent Cardiomyocyte Apoptosis. AB - BACKGROUND/AIMS: Endoplasmic reticulum stress (ERS) plays an important role in the progression of acute myocardial infarction (AMI), in part by mediating apoptosis. Polyamines, including putrescine, spermidine, and spermine, are polycations with anti-oxidative, anti-aging, and cell growth-promoting activities. This study aimed to determine the mechanisms by which spermine protects against ERS-induced apoptosis in rats following AMI. METHODS AND RESULTS: AMI was established by ligation of the left anterior descending coronary artery (LAD) in rats, and exogenous spermine was administered by intraperitoneal injection (2.5 mg/ml daily for 7 days pre-AMI). Spermine treatment limited infarct size, attenuated cardiac troponin I and creatinine kinase-MB release, improved cardiac function, and decreased ERS and apoptosis related protein expression. Isolated cardiomyocytes subjected to hypoxia showed significant increase in reactive oxygen species (ROS) and the expression of apoptosis and ERS related proteins; these effects occurred through PERK and eIF2alpha phosphorylation. The addition of spermine attenuated cardiomyocyte apoptosis, suppressed the production of ROS, and inhibited ERS related pathways. CONCLUSIONS: Spermine was an effective pre-treatment strategy to attenuate cardiac ERS injury in rats, and the cardioprotective mechanism occurring through inhibition of ROS production and down regulation of the PERK-eIF2alpha pathway. These findings provide a novel target for the prevention of apoptosis in the setting of AMI. PMID- 26828927 TI - Role of Decorin Core Protein in Collagen Organisation in Congenital Stromal Corneal Dystrophy (CSCD). AB - The role of Decorin in organising the extracellular matrix was examined in normal human corneas and in corneas from patients with Congenital Stromal Corneal Dystrophy (CSCD). In CSCD, corneal clouding occurs due to a truncating mutation (c.967delT) in the decorin (DCN) gene. Normal human Decorin protein and the truncated one were reconstructed in silico using homology modelling techniques to explore structural changes in the diseased protein. Corneal CSCD specimens were also examined using 3-D electron tomography and Small Angle X-ray diffraction (SAXS), to image the collagen-proteoglycan arrangement and to quantify fibrillar diameters, respectively. Homology modelling showed that truncated Decorin had a different spatial geometry to the normal one, with the truncation removing a major part of the site that interacts with collagen, compromising its ability to bind effectively. Electron tomography showed regions of abnormal stroma, where collagen fibrils came together to form thicker fibrillar structures, showing that Decorin plays a key role in the maintenance of the order in the normal corneal extracellular matrix. Average diameter of individual fibrils throughout the thickness of the cornea however remained normal. PMID- 26828928 TI - Unraveling the Tissue-Specific Gene Signatures of Gilthead Sea Bream (Sparus aurata L.) after Hyper- and Hypo-Osmotic Challenges. AB - A custom microarray was used for the transcriptomic profiling of liver, gills and hypothalamus in response to hypo- (380/00 -> 50/00) or hyper- (380/00 -> 550/00) osmotic challenges (7 days after salinity transfer) in gilthead sea bream (Sparus aurata) juveniles. The total number of differentially expressed genes was 777. Among them, 341 and 310 were differentially expressed in liver after hypo- and hyper-osmotic challenges, respectively. The magnitude of changes was lower in gills and hypothalamus with around 131 and 160 responsive genes in at least one osmotic stress condition, respectively. Regardless of tissue, a number of genes were equally regulated in either hypo- and hyper-osmotic challenges: 127 out of 524 in liver, 11 out of 131 in gills and 19 out of 160 in hypothalamus. In liver and gills, functional analysis of differentially expressed genes recognized two major clusters of overlapping canonical pathways that were mostly related to "Energy Metabolism" and "Oxidative Stress". The later cluster was represented in all the analyzed tissues, including the hypothalamus, where differentially expressed genes related to "Cell and tissue architecture" were also over represented. Overall the response for "Energy Metabolism" was the up-regulation, whereas for oxidative stress-related genes the type of response was highly dependent of tissue. These results support common and different osmoregulatory responses in the three analyzed tissues, helping to load new allostatic conditions or even to return to basal levels after hypo- or hyper-osmotic challenges according to the different physiological role of each tissue. PMID- 26828930 TI - Assessing Projection Bias in Consumers' Food Preferences. AB - The aim of this study is to test whether projection bias exists in consumers' purchasing decisions for food products. To achieve our aim, we used a non hypothetical experiment (i.e., experimental auction), where hungry and non-hungry participants were incentivized to reveal their willingness to pay (WTP). The results confirm the existence of projection bias when consumers made their decisions on food products. In particular, projection bias existed because currently hungry participants were willing to pay a higher price premium for cheeses than satiated ones, both in hungry and satiated future states. Moreover, participants overvalued the food product more when they were delivered in the future hungry condition than in the satiated one. Our study provides clear, quantitative and meaningful evidence of projection bias because our findings are based on economic valuation of food preferences. Indeed, the strength of this study is that findings are expressed in terms of willingness to pay which is an interpretable amount of money. PMID- 26828929 TI - A Phylogenomic Approach Based on PCR Target Enrichment and High Throughput Sequencing: Resolving the Diversity within the South American Species of Bartsia L. (Orobanchaceae). AB - Advances in high-throughput sequencing (HTS) have allowed researchers to obtain large amounts of biological sequence information at speeds and costs unimaginable only a decade ago. Phylogenetics, and the study of evolution in general, is quickly migrating towards using HTS to generate larger and more complex molecular datasets. In this paper, we present a method that utilizes microfluidic PCR and HTS to generate large amounts of sequence data suitable for phylogenetic analyses. The approach uses the Fluidigm Access Array System (Fluidigm, San Francisco, CA, USA) and two sets of PCR primers to simultaneously amplify 48 target regions across 48 samples, incorporating sample-specific barcodes and HTS adapters (2,304 unique amplicons per Access Array). The final product is a pooled set of amplicons ready to be sequenced, and thus, there is no need to construct separate, costly genomic libraries for each sample. Further, we present a bioinformatics pipeline to process the raw HTS reads to either generate consensus sequences (with or without ambiguities) for every locus in every sample or--more importantly--recover the separate alleles from heterozygous target regions in each sample. This is important because it adds allelic information that is well suited for coalescent-based phylogenetic analyses that are becoming very common in conservation and evolutionary biology. To test our approach and bioinformatics pipeline, we sequenced 576 samples across 96 target regions belonging to the South American clade of the genus Bartsia L. in the plant family Orobanchaceae. After sequencing cleanup and alignment, the experiment resulted in ~25,300 bp across 486 samples for a set of 48 primer pairs targeting the plastome, and ~13,500 bp for 363 samples for a set of primers targeting regions in the nuclear genome. Finally, we constructed a combined concatenated matrix from all 96 primer combinations, resulting in a combined aligned length of ~40,500 bp for 349 samples. PMID- 26828931 TI - Counterfactual Reasoning Deficits in Schizophrenia Patients. AB - BACKGROUND: Counterfactual thinking is a specific type of conditional reasoning that enables the generation of mental simulations of alternatives to past factual events. Although it has been broadly studied in the general population, research on schizophrenia is still scarce. The aim of the current study was to further examine counterfactual reasoning in this illness. METHODS: Forty schizophrenia patients and 40 controls completed a series of tests that assessed the influence of the "causal order effect" on counterfactual thinking, and the ability to generate counterfactual thoughts and counterfactually derive inferences from a hypothetical situation. Socio-demographic and clinical characteristics, as well as neurocognitive variables, were also examined. RESULTS: Compared to controls, the schizophrenia patients generated fewer counterfactual thoughts when faced with a simulated scenario. The pattern of response when assessing the causality effect of the order was also different between the groups, with the patients being more frequently unable to attribute any ordering of events than the control subjects. Additionally, the schizophrenia patients showed more difficulties when deriving normative counterfactual inferences from hypothetical social situations. None of the counterfactual reasoning measures was associated to any of the cognitive functions or clinical and socio-demographic variables assessed. CONCLUSIONS: A global impairment in counterfactual thinking characterizes schizophrenia patients. Because of the potential impact of such deficits on psychosocial functioning, targeting counterfactual reasoning for improvement might be considered in future treatment approaches. PMID- 26828933 TI - Legal Professionals' Knowledge of Eyewitness Testimony in China: A Cross Sectional Survey. AB - PURPOSE: To examine legal professionals' knowledge of a wide range of factors that affect eyewitness accuracy in China. METHODS: A total of 812 participants, including 210 judges, 244 prosecutors, 202 police officers, and 156 defense attorneys, were asked to respond to 12 statements about eyewitness testimony and 3 basic demographic questions (i.e., gender, age, and prior experience). RESULTS: Although the judges and the defense attorneys had a somewhat higher number of correct responses than the other two groups, all groups showed limited knowledge of eyewitness testimony. In addition, the participants' responses to only four items (i.e., weapon focus, attitude and expectations, child suggestibility, and the impact of stress) were roughly unanimous within the four legal professional groups. Legal professionals' gender showed no significant correlations with their knowledge of eyewitness testimony. Prior experiences were significantly and negatively correlated with the item on the knowledge of forgetting curve among judges but positively correlated with two items (i.e., attitudes and exposure time) among defense attorneys and with 4 statements (i.e., the knowledge of attitudes and expectations, impact of stress, child witness accuracy, and exposure time) among prosecutors. CONCLUSIONS: The findings suggest that knowledge of the factors that influence eyewitness accuracy must be more effectively communicated to legal professionals in the future. PMID- 26828932 TI - The Zinc-Finger Protein SOP1 Is Required for a Subset of the Nuclear Exosome Functions in Arabidopsis. AB - Correct gene expression requires tight RNA quality control both at transcriptional and post-transcriptional levels. Using a splicing-defective allele of PASTICCINO2 (PAS2), a gene essential for plant development, we isolated suppressor mutations modifying pas2-1 mRNA profiles and restoring wild-type growth. Three suppressor of pas2 (sop) mutations modified the degradation of mis spliced pas2-1 mRNA species, allowing the synthesis of a functional protein. Cloning of the suppressor mutations identified the core subunit of the exosome SOP2/RRP4, the exosome nucleoplasmic cofactor SOP3/HEN2 and a novel zinc-finger protein SOP1 that colocalizes with HEN2 in nucleoplasmic foci. The three SOP proteins counteract post-transcriptional (trans)gene silencing (PTGS), which suggests that they all act in RNA quality control. In addition, sop1 mutants accumulate some, but not all of the misprocessed mRNAs and other types of RNAs that are observed in exosome mutants. Taken together, our data show that SOP1 is a new component of nuclear RNA surveillance that is required for the degradation of a specific subset of nuclear exosome targets. PMID- 26828934 TI - Experimental Adaptation of Rotaviruses to Tumor Cell Lines. AB - A number of viruses show a naturally extended tropism for tumor cells whereas other viruses have been genetically modified or adapted to infect tumor cells. Oncolytic viruses have become a promising tool for treating some cancers by inducing cell lysis or immune response to tumor cells. In the present work, rotavirus strains TRF-41 (G5) (porcine), RRV (G3) (simian), UK (G6-P5) (bovine), Ym (G11-P9) (porcine), ECwt (murine), Wa (G1-P8), Wi61 (G9) and M69 (G8) (human), and five wild-type human rotavirus isolates were passaged multiple times in different human tumor cell lines and then combined in five different ways before additional multiple passages in tumor cell lines. Cell death caused by the tumor cell-adapted isolates was characterized using Hoechst, propidium iodide, 7-AAD, Annexin V, TUNEL, and anti-poly-(ADP ribose) polymerase (PARP) and -phospho histone H2A.X antibodies. Multiple passages of the combined rotaviruses in tumor cell lines led to a successful infection of these cells, suggesting a gain-of function by the acquisition of greater infectious capacity as compared with that of the parental rotaviruses. The electropherotype profiles suggest that unique tumor cell-adapted isolates were derived from reassortment of parental rotaviruses. Infection produced by such rotavirus isolates induced chromatin modifications compatible with apoptotic cell death. PMID- 26828935 TI - Willingness-to-Pay for Community-Based Health Insurance among Informal Workers in Urban Bangladesh. AB - INTRODUCTION: Reliance on out-of-pocket payment for healthcare may lead poor households to undertake catastrophic health expenditure, and risk-pooling mechanisms have been recommended to mitigate such burdens for households in Bangladesh. About 88% of the population of Bangladesh depends on work in the informal sector. We aimed to estimate willingness-to-pay (WTP) for CBHI and identify its determinants among three categories of urban informal workers rickshaw-pullers, shopkeepers and restaurant workers. METHODS: The bidding game version of contingent valuation method was used to estimate weekly WTP. In three urban locations 557 workers were interviewed using a structured questionnaire during 2010 and 2011. Multiple-regression analysis was used to predict WTP by demographic and household characteristics, occupation, education level and past illness. RESULTS: WTP for a CBHI scheme was expressed by 86.7% of informal workers. Weekly average WTP was 22.8 BDT [Bangladeshi Taka; 95% confidence interval (CI) 20.9-24.8] or 0.32 USD and varied significantly across occupational groups (p = 0.000) and locations (p = 0.003). WTP was highest among rickshaw pullers (28.2 BDT or 0.40 USD; 95% CI: 24.7-31.7), followed by restaurant workers (20.4 BDT 0.29 USD; 95% CI: 17.0-23.8) and shopkeepers (19.2 BDT or 0.27 USD; 95% CI: 16.1-22.4). Multiple regression analysis identified monthly income, occupation, geographical location and educational level as the key determinants of WTP. WTP increased 0.196% with each 1% increase in monthly income, and was 26.9% lower among workers with up to a primary level of education versus those with higher than primary, but less than one year of education. CONCLUSION: Informal workers in urban areas thus are willing to pay for CBHI and socioeconomic differences explain the magnitude of WTP. The policy maker might think introducing community-based model including public-community partnership model for healthcare financing of informal workers. Decision making regarding the implementation of such schemes should consider worker location and occupation. PMID- 26828936 TI - Genital Lichen Sclerosus in Male Patients: A New Treatment with Polydeoxyribonucleotide. AB - Lichen sclerosus (LS) is an inflammatory and chronic disease that causes itching, pain, dysuria, urinary retention, dyspareunia and sexual dysfunction, in both men and women. The first line pharmacological treatment is based on the use of topical steroids, which have proved their efficacy in 60-70% of cases but with a high rate of relapses in time (50-80% of the patients of both sexes). The purpose of our non-randomised prospective pilot study was to evaluate the efficacy and tolerability of a new loco regional therapy with polydeoxyribonucleotides (PDRN) in the treatment of male genital LS. PDRN is an healing and anti-dystrophic drug with anti-inflammatory effects, through the reduction of cytokine. Twenty one male patients suffering from genital LS were recruited. All the patients were submitted to treatment using loco-regional intradermal injections with PDRN. Dermatology Life Quality Index (DLQI), International Index of Erectile Function (IIEF-5) and PGI-I questionnaires were administered at baseline and at the end of treatment in order to evaluate the results of this treatment. The statistical evaluation of the data obtained with the DLQI questionnaire showed a marked improvement of the overall conditions in terms of quality of life, with an average change of scores from 15 to 4 (p < 0.0001). PGI-I questionnaire showed that 80% of the patients treated considered their post-treatment conditions as 'improved'. There was no significant change in terms of sexual function according to the IIEF questionnaire (p = 0.189). The results obtained show the excellent tolerability and the therapeutic efficacy of PDRN, with clear improvement of the local symptoms and of the quality of life. PMID- 26828937 TI - The Effect of Weight Loss on the Muscle Proteome in the Damara, Dorper and Australian Merino Ovine Breeds. AB - Seasonal Weight Loss (SWL) is an important constraint, limiting animal production in the Tropics and the Mediterranean. As a result, the study of physiological and biochemical mechanisms by which domestic animal breeds respond to SWL is important to those interested in animal breeding and the improvement thereof. To that end, the study of the proteome has been instrumental in gathering important information on physiological mechanisms, including those underlying SWL. In spite of that, little information is available concerning physiological mechanisms of SWL in production animals. The objective of this study was to determine differential protein expression in the muscle of three different breeds of sheep, the Australian Merino, the Dorper and the Damara, each showing different levels of tolerance to weight loss (low, medium and high, respectively). Per breed, two experimental groups were established, one labeled "Growth" and the other labeled "Restricted." After forty-two days of dietary treatment, all animals were euthanized. Muscle samples were then taken. Total protein was extracted from the muscle, then quantified and two-dimensional gel electrophoresis were conducted using 24 cm pH 3-10 immobiline dry strips and colloidal coomassie staining. Gels were analyzed using Samespots(r) software and spots of interest were in-gel digested with trypsin. The isolated proteins were identified using MALDI-TOF/TOF. Results indicated relevant differences between breeds; several proteins are suggested as putative biomarkers of tolerance to weight loss: Desmin, Troponin T, Phosphoglucomutase and the Histidine Triad nucleotide-binding protein 1. This information is of relevance to and of possible use in selection programs aiming towards ruminant animal production in regions prone to droughts and weight loss. PMID- 26828938 TI - Apoptosis of THP-1 Macrophages Induced by Pseudohypericin-Mediated Sonodynamic Therapy Through the Mitochondria-Caspase Pathway. AB - BACKGROUND/AIMS: Pseudohypericin (P-HY) and its congener hypericin are the major hydroxylated phenanthroperylenediones present in Hypericum species. Our previous study indicated that hypericin was able to function as a sonosensitizer. The potential use of P-HY as a sonosensitizer for sonodynamic therapy (SDT) requires further exploration. Thus, this study aimed to investigate the effects of P-HY SDT on THP-1 macrophages. METHODS: THP-1 macrophages were incubated with P-HY, and cell viability was measured using a CCK-8 assay. Fluorescence microscopy assessed the intracellular reactive oxygen species (ROS), mitochondrial membrane potential (DeltaPsim ) and mitochondrial permeability transition pore (mPTP) opening. Apoptotic and necrotic cell levels were measured by the flow cytometry analysis. Western blots were employed to assay BAX, Cytochrome C expression and apoptosis-related proteins. RESULTS: P-HY-SDT induced THP-1 macrophage apoptosis. The levels of ROS were significantly increased in the SDT group, resulting in both mPTP opening and DeltaPsim loss, which led to apoptosis. In addition, the translocation of BAX, release of Cytochrome C and the upregulated expression of apoptosis-related proteins after P-HY-SDT were observed, all of which were reversed by N-acetyl cysteine (NAC). CONCLUSION: P-HY-SDT induced THP-1 macrophage apoptosis through the mitochondria-caspase pathway via ROS generation, the translocation of BAX and the release of Cytochrome C to regulate the mPTP opening. PMID- 26828940 TI - Confirmation of Single-Locus Sex Determination and Female Heterogamety in Willow Based on Linkage Analysis. AB - In this study, we constructed high-density genetic maps of Salix suchowensis and mapped the gender locus with an F1 pedigree. Genetic maps were separately constructed for the maternal and paternal parents by using amplified fragment length polymorphism (AFLP) markers and the pseudo-testcross strategy. The maternal map consisted of 20 linkage groups that spanned a genetic distance of 2333.3 cM; whereas the paternal map contained 21 linkage groups that covered 2260 cM. Based on the established genetic maps, it was found that the gender of willow was determined by a single locus on linkage group LG_03, and the female was the heterogametic gender. Aligned with mapped SSR markers, linkage group LG_03 was found to be associated with chromosome XV in willow. It is noteworthy that marker density in the vicinity of the gender locus was significantly higher than that expected by chance alone, which indicates severe recombination suppression around the gender locus. In conclusion, this study confirmed the findings on the single locus sex determination and female heterogamety in willow. It also provided additional evidence that validated the previous studies, which found that different autosomes evolved into sex chromosomes between the sister genera of Salix (willow) and Populus (poplar). PMID- 26828941 TI - Gait Transitions in Human Infants: Coping with Extremes of Treadmill Speed. AB - Spinal pattern generators in quadrupedal animals can coordinate different forms of locomotion, like trotting or galloping, by altering coordination between the limbs (interlimb coordination). In the human system, infants have been used to study the subcortical control of gait, since the cerebral cortex and corticospinal tract are immature early in life. Like other animals, human infants can modify interlimb coordination to jump or step. Do human infants possess functional neuronal circuitry necessary to modify coordination within a limb (intralimb coordination) in order to generate distinct forms of alternating bipedal gait, such as walking and running? We monitored twenty-eight infants (7 12 months) stepping on a treadmill at speeds ranging between 0.06-2.36 m/s, and seventeen adults (22-47 years) walking or running at speeds spanning the walk-to run transition. Six of the adults were tested with body weight support to mimic the conditions of infant stepping. We found that infants could accommodate a wide range of speeds by altering stride length and frequency, similar to adults. Moreover, as the treadmill speed increased, we observed periods of flight during which neither foot was in ground contact in infants and in adults. However, while adults modified other aspects of intralimb coordination and the mechanics of progression to transition to a running gait, infants did not make comparable changes. The lack of evidence for distinct walking and running patterns in infants suggests that the expression of different functional, alternating gait patterns in humans may require neuromuscular maturation and a period of learning post-independent walking. PMID- 26828939 TI - Graded Proteasome Dysfunction in Caenorhabditis elegans Activates an Adaptive Response Involving the Conserved SKN-1 and ELT-2 Transcription Factors and the Autophagy-Lysosome Pathway. AB - The maintenance of cellular proteins in a biologically active and structurally stable state is a vital endeavor involving multiple cellular pathways. One such pathway is the ubiquitin-proteasome system that represents a major route for protein degradation, and reductions in this pathway usually have adverse effects on the health of cells and tissues. Here, we demonstrate that loss-of-function mutants of the Caenorhabditis elegans proteasome subunit, RPN-10, exhibit moderate proteasome dysfunction and unexpectedly develop both increased longevity and enhanced resistance to multiple threats to the proteome, including heat, oxidative stress, and the presence of aggregation prone proteins. The rpn-10 mutant animals survive through the activation of compensatory mechanisms regulated by the conserved SKN-1/Nrf2 and ELT-2/GATA transcription factors that mediate the increased expression of genes encoding proteasome subunits as well as those mediating oxidative- and heat-stress responses. Additionally, we find that the rpn-10 mutant also shows enhanced activity of the autophagy-lysosome pathway as evidenced by increased expression of the multiple autophagy genes including atg-16.2, lgg-1, and bec-1, and also by an increase in GFP::LGG-1 puncta. Consistent with a critical role for this pathway, the enhanced resistance of the rpn-10 mutant to aggregation prone proteins depends on autophagy genes atg-13, atg-16.2, and prmt-1. Furthermore, the rpn-10 mutant is particularly sensitive to the inhibition of lysosome activity via either RNAi or chemical means. We also find that the rpn-10 mutant shows a reduction in the numbers of intestinal lysosomes, and that the elt-2 gene also plays a novel and vital role in controlling the production of functional lysosomes by the intestine. Overall, these experiments suggest that moderate proteasome dysfunction could be leveraged to improve protein homeostasis and organismal health and longevity, and that the rpn-10 mutant provides a unique platform to explore these possibilities. PMID- 26828942 TI - Primary adherence to antidepressant prescriptions in primary health care: a population-based study in Sweden. AB - BACKGROUND: Medical adherence is important in the treatment of depression. Primary medical adherence, i.e. patients collecting their newly prescribed medications from pharmacies, is very different depending on the drug prescribed OBJECTIVE: To assess the rate of primary medical adherence in patients prescribed antidepressants and to identify characteristics that make patients less likely to pick up prescriptions. METHODS: An observational study was performed using primary health care data from Sweden on patients who were prescribed antidepressants. Univariate and multivariate logistic regression was used to determine differences in pick-up rate according to patient characteristics. MAIN OUTCOME: Pick-up rate, defined as collection of a prescription within 30 days. RESULTS: A total of 11 624 patients received an antidepressant prescription during the study period, and the overall pick-up rate was 85.1%. The pick-up rate differed according to country of birth: individuals born in the Middle East and other countries outside Europe had lower primary medical adherence than Swedes, with adjusted odds ratios (ORs) of 0.58 and 0.67, respectively. Patients at ages 64-79 years had a higher pick-up rate compared with those aged 25-44 years (OR 1.71). Divorced patients had a lower rate compared with married patients (OR 0.80). CONCLUSION: Immigrants from the Middle East and other countries outside Europe and younger and divorced patients had lower primary medical adherence, which calls for clinical attention and preventive measures. KEY POINTS Primary medical adherence is important in the treatment of depression. Are patient characteristics associated with primary medical adherence? The overall primary medical adherence rate was 85%. The rate differed by country of birth, age at diagnosis of depression, and marital status. Clinical attention is needed in patients who do not pick up their antidepressants. PMID- 26828943 TI - Mean Platelet Volume May Not Be Related to Benign Prostatic Hyperplasia or Lower Urinary Tract Symptoms. PMID- 26828944 TI - Chest Pain after Aortic Valve Replacement: Rupture of Right Sinus of Valsalva Presenting as Myocardial Infarction. AB - BACKGROUND: A 47-year-old male presented with retrosternal chest pain, which had started 4 days previously and had become excruciating for the past 6 h. He had undergone mechanical aortic valve replacement surgery 4 months previously. INVESTIGATION: Electrocardiography, echocardiography, computed tomography angiography of the aorta. DIAGNOSIS: Rupture of the right sinus of Valsalva and right coronary artery dissection. MANAGEMENT: The defect in the right coronary sinus was closed, and the dissection at the root of the right coronary artery was resected and the right coronary artery bypassed to the root of the aorta. PMID- 26828945 TI - Evidence for the Nucleo-Apical Shuttling of a Beta-Catenin Like Plasmodium falciparum Armadillo Repeat Containing Protein. AB - Eukaryotic Armadillo (ARM) repeat proteins are multifaceted with prominent roles in cell-cell adhesion, cytoskeletal regulation and intracellular signaling among many others. One such ARM repeat containing protein, ARM Repeats Only (ARO), has recently been demonstrated in both Toxoplasma (TgARO) and Plasmodium (PfARO) parasites to be targeted to the rhoptries during the late asexual stages. TgARO has been implicated to play an important role in rhoptry positioning i.e. directing the rhoptry towards the apical end of the parasite. Here, we report for the first time that PfARO exhibits a DNA binding property and a dynamic sub cellular localization between the nucleus (early schizont) and rhoptry (late schizont) during the different stages of the asexual blood-stage life cycle. PfARO possesses a putative nuclear export signal (NES) and the nucleo-apical shuttling was sensitive to Leptomycin B (LMB) suggesting that the nuclear export was mediated by CRM1. Importantly, PfARO specifically bound an A-T rich DNA sequence of the P. falciparum Gyrase A (PfgyrA) gene, suggesting that the DNA binding specificity of PfARO is likely due to the AT-richness of the probe. This is a novel functional characteristic that has not been reported previously for any P. falciparum ARM containing protein and suggests a putative role for PfARO in gene regulation. This study describes for the first time a conserved P. falciparum ARM repeat protein with a high degree of functional versatility. PMID- 26828946 TI - A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy. AB - Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of peripheral neuropathies with diverse genetic causes. In this study, we identified p.I43N mutation in PMP2 from a family exhibiting autosomal dominant demyelinating CMT neuropathy by whole exome sequencing and characterized the clinical features. The age at onset was the first to second decades and muscle atrophy started in the distal portion of the leg. Predominant fatty replacement in the anterior and lateral compartment was similar to that in CMT1A caused by PMP22 duplication. Sural nerve biopsy showed onion bulbs and degenerating fibers with various myelin abnormalities. The relevance of PMP2 mutation as a genetic cause of dominant CMT1 was assessed using transgenic mouse models. Transgenic mice expressing wild type or mutant (p.I43N) PMP2 exhibited abnormal motor function. Electrophysiological data revealed that both mice had reduced motor nerve conduction velocities (MNCV). Electron microscopy revealed that demyelinating fibers and internodal lengths were shortened in both transgenic mice. These data imply that overexpression of wild type as well as mutant PMP2 also causes the CMT1 phenotype, which has been documented in the PMP22. This report might expand the genetic and clinical features of CMT and a further mechanism study will enhance our understanding of PMP2-associated peripheral neuropathy. PMID- 26828947 TI - A Wireless EEG Recording Method for Rat Use inside the Water Maze. AB - With the continued miniaturisation of portable embedded systems, wireless EEG recording techniques are becoming increasingly prevalent in animal behavioural research. However, in spite of their versatility and portability, they have seldom been used inside water-maze tasks designed for rats. As such, a novel 3D printed implant and waterproof connector is presented, which can facilitate wireless water-maze EEG recordings in freely-moving rats, using a commercial wireless recording system (W32; Multichannel Systems). As well as waterproofing the wireless system, battery, and electrode connector, the implant serves to reduce movement-related artefacts by redistributing movement-related forces away from the electrode connector. This implant/connector was able to successfully record high-quality LFP in the hippocampo-striatal brain regions of rats as they undertook a procedural-learning variant of the double-H water-maze task. Notably, there were no significant performance deficits through its use when compared with a control group across a number of metrics including number of errors and speed of task completion. Taken together, this method can expand the range of measurements that are currently possible in this diverse area of behavioural neuroscience, whilst paving the way for integration with more complex behaviours. PMID- 26828948 TI - Robust Metal-Organic Framework Containing Benzoselenadiazole for Highly Efficient Aerobic Cross-dehydrogenative Coupling Reactions under Visible Light. AB - A zirconium(IV)-based UiO-topological metal-organic framework (UiO-68Se) containing benzoselenadiazole was synthesized by an approach of the mixed dicarboxylate struts, which show highly efficient and recycalable photocatalytic activity for aerobic cross-dehydrogenative coupling reactions between tertiary amines and various carbon nucleophiles under visible-light irradiation. PMID- 26828949 TI - [Co5Tp*4(Me2bta)6]: A Highly Symmetrical Pentanuclear Kuratowski Complex Featuring Tris(pyrazolyl)borate and Benzotriazolate Ligands. AB - The pentanuclear Co(II) complex [Co5Tp*4(Me2bta)6] containing N-donor ligands (5,6-dimethyl benzotriazolate; Me2bta6) and N-donor capping ligands (tris(3,5 dimethyl-1-pyrazolyl)borate; Tp*) was prepared by a simple and efficient ligand exchange reaction from [Co5Cl4(Me2bta)6] and tetra-n-butyl ammonium tris(3,5 dimethyl-1-pyrazolyl)borate. Compared to the precursor complex [Co5Cl4(Me2bta)6], which contains one Co(II) ion in octahedral and four Co(II) ions in tetrahedral coordination geometry, the title compound features all five Co(II) ions in an octahedral coordination environment while keeping a high complex symmetry. This results in modified properties including improved solubility and distinct magnetic behavior as compared to the precursor complex. The molecular structure and phase purity of the compound was verified by XRPD, UV-vis, ESI-MS, IR, and NMR measurements. Thermal stability of the compound was determined via TGA. The magnetic properties of here reported novel complex [Co5Tp*4(Me2bta)6] as well as its precursor [Co5Cl4(Me2bta)6] were examined in detail via ESR and SQUID measurements, which indicated weak anti-ferromagnetic exchange interactions between high-spin Co(II) centers at T < 20 and 50 K, respectively. PMID- 26828950 TI - Single-Crystal to Single-Crystal Phase Transition and Segmented Thermochromic Luminescence in a Dynamic 3D Interpenetrated Ag(I) Coordination Network. AB - A new 3D Ag(I)-based coordination network, [Ag2(pz)(bdc).H2O]n (1; pz = pyrazine and H2bdc = benzene-1,3-dicarboxylic acid), was constructed by one-pot assembly and structurally established by single-crystal X-ray diffraction at different temperatures. Upon cooling from 298 to 93 K, 1 undergo an interesting single crystal to single-crystal phase transition from orthorhombic Ibca (Z = 16) to Pccn (Z = 32) at around 148 K. Both phases show a rare 2-fold-interpenetrated 4 connected lvt network but incorporate different [Ag2(COO)2] dimeric secondary building units. It is worth mentioning that complex 1 shows red- and blue-shifted luminescences in the 290-170 and 140-80 K temperature ranges, respectively. The variable-temperature single-crystal X-ray crystallographic studies suggest that the argentophilic interactions and rigidity of the structure dominated the luminescence chromism trends at the respective temperature ranges. Upon being mechanically ground, 1 exhibits a slight mechanoluminescence red shift from 589 to 604 nm at 298 K. PMID- 26828951 TI - Serological and Entomological Study of Dengue in Dang and Chitwan Districts of Nepal. AB - A descriptive cross-sectional study was carried out among 264 suspected dengue patients in two districts (Dang and Chitwan) of Nepal from June 2013 to November 2013. The anti-dengue IgM positivity was found to be (51/264)19.31% by capture ELISA, of which 21 (41.2%) were male and 30 (58.8%) were female. Symptoms of seropositive cases were fever, anorexia, nausea, headache, retro-orbital pain, skin rashes, and myalgia. Hematological features like thrombocytopenia and leucopenia were found to be significantly associated with the dengue fever (DF). Discarded tires were found as the commonest breeding habitats for the dengue vectors. Higher sero-positivity was recorded from the area having higher Breteau index (BI). The pH, chloride ion concentration and the salinity of the water from breeding habitats were found to be ranging from 6.9+/-0.82 to 8, 103.33+/-17.52 mg/L to 140.65 mg/L, and 0.19+/-0.032 ppt to 0.25 ppt respectively. This study may be helpful for the health authorities and public health workers for early diagnosis of DF and for the improved preventive measures to be adopted in the epidemic and possible epidemic areas. PMID- 26828952 TI - Participation of D-serine in the development and reproduction of the silkworm Bombyx mori. AB - The silkworm Bombyx mori contains high concentrations of free D-serine, an optical isomer of L-serine. To elucidate its function, we first investigated the localization of D-serine in various organs of silkworm larvae, pupae, and adult moths. Using immunohistochemical analysis with an anti-D-serine antibody, we found D-serine in the microvilli of midgut goblet and cylindrical cells and in peripheral matrix components of testicular and ovarian cells. By spectrophotometric analysis, D-serine was also found in the hemolymph and fat body. D-Alanine was not detected in the various organs by immunohistochemistry. Serine racemase, which catalyzes the inter-conversion of L- and D-serine, was found to co-localize with D-serine, and D-serine production from L-serine by intrinsic serine racemase was suggested. O-Phospho-L-serine is an inhibitor of serine racemase, and it was administered to the larvae to reduce the D-serine level. This reagent decreased the midgut caspase-3 level and caused a delay in spermatogenesis and oogenesis. The reagent also decreased mature sperm and egg numbers, suggesting D-serine participation in these processes. D-Serine administration induced an increase in pyruvate levels in testis, midgut, and fat body, indicating conversion of D-serine to pyruvate. On the basis of these results, together with our previous investigation of ATP biosynthesis in testis, we consider the possible involvement of D-serine in ATP synthesis for metamorphosis and reproduction. PMID- 26828953 TI - Potentiation of Taishan Pinus massoniana pollen polysaccharide on the immune response and protection elicited by a highly pathogenic porcine reproductive and respiratory syndrome virus glycoprotein 5 subunit in pigs. AB - Porcine reproductive and respiratory syndrome virus (PRRSV) heavily affects the global pork industry. Current available vaccine strategies have inherent drawbacks. In this work, the immune enhancement from Taishan Pinus massoniana pollen polysaccharide (TPPPS) and Freund's adjuvant on the efficacy of a PRRSV subunit vaccine were examined. Titers of specific anti-highly pathogenic PRRSV (HP-PRRSV) ELISA antibody and neutralizing antibody were significantly higher in pigs from the groups inoculated with medium- and high-dose TPPPS (mTPPPS, hTPPPS) adjuvant co-administered with a recombinant HP-PRRSV glycoprotein 5 subunit (GP5) than those from other groups (P < 0.05). Pigs inoculated with GP5 + Freund's adjuvant developed severely delayed humoral immune responses specific to GP5 within 28 days post-inoculation (dpi). The groups treated with mTPPPS and hTPPPS adjuvant exhibited the most potent immune enhancement effects on GP5 inoculation with cellular immunity developing, as shown by the level of T lymphocyte proliferation and the percentage of the CD3(+) T lymphocyte subpopulation. Although complete Freund's adjuvant elicited cell-mediated immune responses, the level of T lymphocyte proliferation in this group decreased quickly and no significant differences were observed compared with other adjuvant-alone groups at 56 dpi (P > 0.05). The ratio between CD3(+)CD4(+) and CD3(+)CD8(+) T lymphocyte subpopulations indicated the inoculums of GP5 + mTPPPS and GP5 + hTPPPS induced consistently higher CD3(+)CD4(+) T lymphocyte subpopulations than other inoculums (P < 0.05). The immune responses caused by complete Freund's adjuvant were mainly mediated by CD3(+)CD8(+) T lymphocyte subpopulation (cytotoxic T lymphocytes) in the early stage of inoculation and had no significant difference compared with other adjuvant-alone groups after 28 dpi (P > 0.05). The low-dose TPPPS (lTPPPS) adjuvant also exhibited enhancement effects on humoral immune and T lymphocyte proliferation responses but these were significantly lower than the mTPPPS and hTPPPS doses (P < 0.05). Pigs challenged with HP-PRRSV from the GP5 + mTPPPS, GP5 + hTPPPS, and GP5 + Freund's adjuvant groups showed lower viremia, fewer clinical signs, and fewer pathological lung lesions compared with the groups of GP5-alone and GP5 + lTPPPS (P < 0.05). There were significant differences between the GP5-alone and GP5 + lTPPPS groups in detection indexes after viral challenge (P < 0.05). In conclusion, moderate doses of TPPPS as an adjuvant with GP5 show promise as a candidate for a HP-PRRSV subunit vaccine to efficiently prevent and control HP-PRRSV. PMID- 26828954 TI - A new furanosteroid from Talaromyces sp. lgt-4, a fungal endophyte isolated from Tripterygium wilfordii. AB - Wortmannolol (1), a new furanosteroid, along with five known compounds, wortmannolone (2), ergosterol (3), p-hydroxyphenyl ethanol (4), trans-6-dodecene (5), (2Z, 4E) -5-(8-hydroxy-1,5-dimethyl-3-oxo-6-oxabicyclo [3.2.1] octan-8-yl) 3-methylpenta-2,4-dienoic acid (6) were isolated from a fungal endophyte Talaromyces sp. lgt-4. Their structures were elucidated by IR, MS, 1D and 2D NMR spectra. Compound 1 show weak monoamine oxidase inhibitory activity. PMID- 26828955 TI - Longitudinal control behaviour: Analysis and modelling based on experimental surveys in Italy and the UK. AB - This paper analyses driving behaviour in car-following conditions, based on extensive individual vehicle data collected during experimental field surveys carried out in Italy and the UK. The aim is to contribute to identify simple evidence to be exploited in the ongoing process of driving assistance and automation which, in turn, would reduce rear-end crashes. In particular, identification of differences and similarities in observed car-following behaviours for different samples of drivers could justify common tuning, at a European or worldwide level, of a technological solution aimed at active safety, or, in the event of differences, could suggest the most critical aspects to be taken into account for localisation or customisation of driving assistance solutions. Without intending to be exhaustive, this paper moves one step in this direction. Indeed, driving behaviour and human errors are considered to be among the main crash contributory factors, and a promising approach for safety improvement is the progressive introduction of increasing levels of driving automation in next-generation vehicles, according to the active/preventive safety approach. However, the more advanced the system, the more complex will be the integration in the vehicle, and the interaction with the driver may sometimes become unproductive, or risky, should the driver be removed from the driving control loop. Thus, implementation of these systems will require the interaction of human driving logics with automation logics and then an enhanced ability in modelling drivers' behaviour. This will allow both higher active-safety levels and higher user acceptance to be achieved, thus ensuring that the driver is always in the control loop, even if his/her role is limited to supervising the automatic logic. Currently, the driving mode most targeted by driving assistance systems is longitudinal driving. This is required in various driving conditions, among which car-following assumes key importance because of the huge number of rear-end crashes. The increased availability of lower-cost information and communication technologies (ICTs) has enhanced the possibility of collecting copious and reliable car-following individual vehicle data. In this work, data collected from three different experiments, two carried out in Italy and one in the UK, are analysed and compared. The experiments involved 146 drivers (105 Italian drivers and 41 UK drivers). Data were collected by two instrumented vehicles. Our analysis focused on inter-vehicular spacing in equilibrium car following conditions. We observed that (i) the adopted equilibrium spacing can be fitted using lognormal distributions, (ii) the adopted equilibrium spacing increases with speed, and (iii) the dispersion between drivers increases with speed. In addition, according to different headway thresholds (up to 1 second) a significant number of potentially dangerous behaviours is observed. Three different car-following paradigms are also applied to each of the experiments, and modelling parameters are calibrated and compared to obtain indirect confirmation about the observed similarities and differences in driving behaviour. PMID- 26828956 TI - A novel transthyretin Lys70Glu (p.Lys90Glu) mutation presenting with vitreous amyloidosis and carpal tunnel syndrome. AB - OBJECTIVE: We describe a novel TTR mutation with vitreous opacities and carpal tunnel syndrome. MATERIALS AND METHODS: A 78 year-old woman with vitreous opacities, her daughter with dry eye syndrome, and brother with carpal tunnel syndrome were tested for a mutation in the TTR gene. The vitreous opacities were removed and stained with Congo red and immunohistochemistry against wild type TTR. Skin and gut biopsies and specimens of soft tissue were examined histopathologically. Leukocyte DNA from the proband was analysed by direct sequencing of exons 1 to 4 of the TTR gene and DNA from her daughter and brother using segregation analysis. RESULTS: A point mutation c.268 A>C, in the TTR gene, leading to a missense mutation p.Lys90Glu was found in all subjects. The vitreous opacities were pearl string-like. Histopathology showed red to green birefringence in Congo red, typical to amyloid, and the specimens were immunoreactive with antibodies against TTR. CONCLUSION: We present a novel autosomally inherited Lys90Glu mutation in the TTR gene. This is the first reported FAP family with this mutation in Finland. PMID- 26828957 TI - The geographic distribution of cardiovascular health in the stroke prevention in healthcare delivery environments (SPHERE) study. AB - BACKGROUND: Community-level factors have been clearly linked to health outcomes, but are challenging to incorporate into medical practice. Increasing use of electronic health records (EHRs) makes patient-level data available for researchers in a systematic and accessible way, but these data remain siloed from community-level data relevant to health. PURPOSE: This study sought to link community and EHR data from an older female patient cohort participating in an ongoing intervention at the Ohio State University Wexner Medical Center to associate community-level data with patient-level cardiovascular health (CVH) as well as to assess the utility of this EHR integration methodology. MATERIALS AND METHODS: CVH was characterized among patients using available EHR data collected May through July of 2013. EHR data for 153 patients were linked to United States census-tract level data to explore feasibility and insights gained from combining these disparate data sources. Analyses were conducted in 2014. RESULTS: Using the linked data, weekly per capita expenditure on fruits and vegetables was found to be significantly associated with CVH at the p<0.05 level and three other community-level attributes (median income, average household size, and unemployment rate) were associated with CVH at the p<0.10 level. CONCLUSIONS: This work paves the way for future integration of community and EHR-based data into patient care as a novel methodology to gain insight into multi-level factors that affect CVH and other health outcomes. Further, our findings demonstrate the specific architectural and functional challenges associated with integrating decision support technologies and geographic information to support tailored and patient-centered decision making therein. PMID- 26828958 TI - Structural Analysis and Deletion Mutagenesis Define Regions of QUIVER/SLEEPLESS that Are Responsible for Interactions with Shaker-Type Potassium Channels and Nicotinic Acetylcholine Receptors. AB - Ly6 proteins are endogenous prototoxins found in most animals. They show striking structural and functional parallels to snake alpha-neurotoxins, including regulation of ion channels and cholinergic signaling. However, the structural contributions of Ly6 proteins to regulation of effector molecules is poorly understood. This question is particularly relevant to the Ly6 protein QUIVER/SLEEPLESS (QVR/SSS), which has previously been shown to suppress excitability and synaptic transmission by upregulating potassium (K) channels and downregulating nicotinic acetylcholine receptors (nAChRs) in wake-promoting neurons to facilitate sleep in Drosophila. Using deletion mutagenesis, co immunoprecipitations, ion flux assays, surface labeling and confocal microscopy, we demonstrate that only loop 2 is required for many of the previously described properties of SSS in transfected cells, including interactions with K channels and nAChRs. Collectively our data suggest that QVR/SSS, and by extension perhaps other Ly6 proteins, target effector molecules using limited protein motifs. Mapping these motifs may be useful in rational design of drugs that mimic or suppress Ly6-effector interactions to modulate nervous system function. PMID- 26828959 TI - Distribution of seven heavy metals among hot pepper plant parts. AB - The main objective of this investigation was to monitor concentrations of seven metals (Cd, Pb, Ni, Mo, Cu, Zn, and Cr) in the fruits, leaves, stem, and roots of Capsicum annuum L. (cv. Xcatic) plants grown under four soil management practices: yard waste (YW), sewage sludge (SS), chicken manure (CM), and no-much (NM) bare soil. Elemental analyses were conducted using inductively coupled plasma mass spectrometer. Pb and Cd concentrations in soil amended with YW, SS, and CM were not significantly different (P < 0.05) compared to NM soil, whereas Mo and Cu concentrations were significantly greater in YW compared to SS, CM, and NM treatments. Concentrations of Cd in the fruits of plants grown in NM soil were greater compared to the fruits of plants grown in other treatments. Total Ni concentration (sum of Ni in all plant parts) in plants grown in NM bare soil was greater than in plants grown in SS-, YW-, and CM-amended soils. Values of the bioaccumulation factor indicated that pepper fruits of plants grown in YW, SS, and CM did not show any tendency to accumulate Pb, Cr, and Ni in their edible fruits. PMID- 26828960 TI - Computational models of populations of bacteria and lytic phage. AB - The use of phages to control and reduce numbers of unwanted bacteria can be traced back to the early 1900s, when phages were explored as a tool to treat infections before the wide scale use of antibiotics. Recently, phage therapy has received renewed interest as a method to treat multiresistant bacteria. Phages are also widely used in the food industry to prevent the growth of certain bacteria in foods, and are currently being explored as a tool for use in bioremediation and wastewater treatment. Despite the large body of biological research on phages, relatively little attention has been given to computational modeling of the population dynamics of phage and bacterial interactions. The earliest model was described by Campbell in the 1960s. Subsequent modifications to this model include partial or complete resistance, multiple phage binding sites, and spatial heterogeneity. This review provides a general introduction to modeling of the population dynamics of bacteria and phage. The review introduces the basic model and relevant concepts and evaluates more complex variations of the basic model published to date, including a model of disease epidemics caused by infectious bacteria. Finally, the shortcomings and potential ways to improve the models are discussed. PMID- 26828961 TI - Feasibility study of recycling cephalosporin C fermentation dregs using co composting process with activated sludge as co-substrate. AB - Composting is a potential alternative for cephalosporin C fermentation dregs (CCFDs) compared with incineration process or landfill because of its advantage of recovering nutrients. In this research, CCFDs and activated sludge (AS) were co-composted to analyze the feasibility of recycling the nutrients in CCFDs. A pilot-scale aerobic composting system with an auto-control system was used in this research, and the maturity and security of the compost product were evaluated. The temperature of the composting mixtures was maintained above 55 degrees C for more than 3 days during the composting, indicating that co composting of CCFDs and AS could reach the compost maturity standard, and the seeds germination index (GI) increased from 17.61% to 68.93% by the end of the composting process (28 days). However, the degradation rate of cephalosporin C (CPC) was only 6.58% during the composting process. Monitoring the quality of antibiotic resistance genes (ARGs) in the composts showed that the log copy of blaTEM in the composts increased from 2.15 in the initial phase to 6.37 after 28 days. Long-term investigation of CPC degradation and ARGs variation was conducted for the composts; CPC could still be detected after the maturity phases. A removal efficiency of 49.10% could be achieved in 110 days, while the log copy of ARGs increased to 7.93. Although a higher GI value (>80.00%) was observed, the risk of recycling the CCFDs compost product into land is still high. PMID- 26828963 TI - The bacterial dicarboxylate transporter VcINDY uses a two-domain elevator-type mechanism. AB - Secondary transporters use alternating-access mechanisms to couple uphill substrate movement to downhill ion flux. Most known transporters use a 'rocking bundle' motion, wherein the protein moves around an immobile substrate-binding site. However, the glutamate-transporter homolog GltPh translocates its substrate binding site vertically across the membrane, through an 'elevator' mechanism. Here, we used the 'repeat swap' approach to computationally predict the outward facing state of the Na(+)/succinate transporter VcINDY, from Vibrio cholerae. Our model predicts a substantial elevator-like movement of VcINDY's substrate-binding site, with a vertical translation of ~15 A and a rotation of ~43 degrees . Our observation that multiple disulfide cross-links completely inhibit transport provides experimental confirmation of the model and demonstrates that such movement is essential. In contrast, cross-links across the VcINDY dimer interface preserve transport, thus revealing an absence of large-scale coupling between protomers. PMID- 26828962 TI - A U1 snRNP-specific assembly pathway reveals the SMN complex as a versatile hub for RNP exchange. AB - Despite equal snRNP stoichiometry in spliceosomes, U1 snRNP (U1) is typically the most abundant vertebrate snRNP. Mechanisms regulating U1 overabundance and snRNP repertoire are unknown. In Sm-core assembly, a key snRNP-biogenesis step mediated by the SMN complex, the snRNA-specific RNA-binding protein (RBP) Gemin5 delivers pre-snRNAs, which join SMN-Gemin2-recruited Sm proteins. We show that the human U1-specific RBP U1-70K can bridge pre-U1 to SMN-Gemin2-Sm, in a Gemin5 independent manner, thus establishing an additional and U1-exclusive Sm core assembly pathway. U1-70K hijacks SMN-Gemin2-Sm, enhancing Sm-core assembly on U1s and inhibiting that on other snRNAs, thereby promoting U1 overabundance and regulating snRNP repertoire. SMN-Gemin2's ability to facilitate transactions between different RBPs and RNAs explains its multi-RBP valency and the myriad transcriptome perturbations associated with SMN deficiency in neurodegenerative spinal muscular atrophy. We propose that SMN-Gemin2 is a versatile hub for RNP exchange that functions broadly in RNA metabolism. PMID- 26828965 TI - Molecularly targeted therapy in acute myeloid leukemia. AB - Acute myeloid leukemia (AML) is molecularly heterogeneous. Formerly categorized cytogenetically and molecularly, AML may be classified by genomic and epigenomic analyses. These genetic lesions provide therapeutic targets. Genes targeted currently include mutated FLT3, NPM1 and KIT with drugs entering Phase III trials. Complete remission can be achieved in relapsed/refractory AML, albeit mostly transient. Mutated epigenetic modifiers, including DNMT3A, IDH1/2 and TET2, can be targeted by small molecule inhibitors, hypomethylating agents and histone deacetylase inhibitors. Other agents include cellular signaling pathway inhibitors and monoclonal antibodies against myeloid-associated antigens. Combinatorial strategies appear logical, mostly involving smaller molecular inhibitors partnering with hypomethylating agents. Currently limited to relapsed/refractory AML, targeted therapies are increasingly tested in frontline treatment with or without standard chemotherapy. PMID- 26828964 TI - Crystal structures reveal the molecular basis of ion translocation in sodium/proton antiporters. AB - To fully understand the transport mechanism of Na(+)/H(+) exchangers, it is necessary to clearly establish the global rearrangements required to facilitate ion translocation. Currently, two different transport models have been proposed. Some reports have suggested that structural isomerization is achieved through large elevator-like rearrangements similar to those seen in the structurally unrelated sodium-coupled glutamate-transporter homolog GltPh. Others have proposed that only small domain movements are required for ion exchange, and a conventional rocking-bundle model has been proposed instead. Here, to resolve these differences, we report atomic-resolution structures of the same Na(+)/H(+) antiporter (NapA from Thermus thermophilus) in both outward- and inward-facing conformations. These data combined with cross-linking, molecular dynamics simulations and isothermal calorimetry suggest that Na(+)/H(+) antiporters provide alternating access to the ion-binding site by using elevator-like structural transitions. PMID- 26828966 TI - Effects of Growth Temperature and Postharvest Cooling on Anthocyanin Profiles in Juvenile and Mature Brassica oleracea. AB - The effects of growth temperatures on anthocyanin content and profile were tested on juvenile cabbage and kale plants. The effects of cold storage time were evaluated on both juvenile and mature plants. The anthocyanin content in juvenile plants ranged from 3.82 mg of cyanidin-3,5-diglucoside equivalent (Cy equiv)/g of dry matter (dm) at 25 degrees C to 10.00 mg of Cy equiv/g of dm at 16 degrees C, with up to 76% diacylated anthocyanins. Cold storage of juvenile plants decreased the total amount of anthocyanins but increased the diacylated anthocyanin content by 3-5%. In mature plants, cold storage reduced the total anthocyanin content from 22 to 12.23 mg/g after 5 weeks of storage in red cabbage, while the total anthocyanin content increased after 2 weeks of storage from 2.34 to 3.66 mg of Cy equiv/g of dm in kale without having any effect on acylation in either morphotype. The results obtained in this study will be useful for optimizing anthocyanin production. PMID- 26828967 TI - Best MRI predictors of complete response to neoadjuvant chemoradiation in locally advanced rectal cancer. AB - OBJECTIVE: To identify the MRI parameters which best predict complete response (CR) to neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC) and to assess their diagnostic performance. METHODS: This was a prospective study of pre- and post-CRT MRI and diffusion-weighted imaging (DWI) of 64 patients with LARC who underwent neoadjuvant CRT and subsequent surgery. Histopathological tumour regression grade was the reference standard. Multivariate regression analysis was performed to identify the best MRI predictors of CR to neoadjuvant CRT, and their diagnostic performance was assessed. RESULTS: The study cohort comprised 48 males and 16 females (n = 64), with mean age of 49.48 +/- 14.3 years, range of 23-74 years. 11 patients had pathological complete response. The following factors predicted CR on univariate analysis: low initial (pre-CRT) tumour volume on T2 weighted high-resolution (HR) images and DWI, tumour volume-reduction rate (TVRR) of >95% on DWI and CR on post CRT DWI (ydwiT0) as assessed by the radiologist. However, the best MRI predictors of CR on multivariate regression analysis were CR on post-CRT DWI (ydwiT0) as assessed by the radiologist and TVRR of >95% on DWI, and these parameters had an area under the curve (95% confidence interval) of 0.881 (0.74-1.0) and 0.843 (0.7 0.98), respectively. The sensitivity, specificity, positive-predictive value, negative-predictive value and accuracy of DWI in predicting CR was 81.8%, 94.3%, 75%, 96.1% and 76%; the sensitivity, specificity and accuracy of TVRR of >95% as a predictor of CR was 80%, 84.1% and 64.1%, respectively; however, this difference was not statistically significant. The interobserver agreement was substantial for ydwiT0. CONCLUSION: Visual assessment of CR on post-CRT DWI and TVRR of >95% on DWI were the best predictors of CR after neoadjuvant CRT in patients with LARC, and the former being more practical can be used in daily practice. ADVANCES IN KNOWLEDGE: In rectal cancer, ydwiT0 as assessed by the radiologist was the best and most practical imaging predictor of CR and scores over standard T2W HR images. PMID- 26828968 TI - Modic changes in lumbar spine: prevalence and distribution patterns of end plate oedema and end plate sclerosis. AB - OBJECTIVE: The purpose of this study is to evaluate the distribution of end plate oedema in different types of Modic change especially in mixed type and to analyze the presence of end plate sclerosis in various types of Modic change. MATERIALS AND METHODS: 276 patients with low back pain were scanned with 1.5-T MRI. Three radiologists assessed the MR images by T1 weighted, T2 weighted and fat saturation T2 weighted sequences and classified them according to the Modic changes. Pure oedematous end plate signal changes were classified as Modic Type I; pure fatty end plate changes were classified as Modic Type II; and pure sclerotic end plate changes as Modic Type III. A mixed feature of both Types I and II with predominant oedematous signal change is classified as Modic I-II, and a mixture of Types I and II with predominant fatty change is classified as Modic II-I. Thus, the mixed types can further be subdivided into seven subtypes: Types I-II, Types II-I, Types I-III, Types III-I, Types II-III, Types III-II and Types I-III. During the same period, 52 of 276 patients who underwent CT and MRI were retrospectively reviewed to determine end plate sclerosis. RESULTS: (1) End plate oedema: of the 2760 end plates (276 patients) examined, 302 end plates showed Modic changes, of which 82 end plates showed mixed Modic changes. The mixed Modic changes contain 92.7% of oedematous changes. The mixed types especially Types I II and Types II-I made up the majority of end plate oedematous changes. (2) End plate sclerosis: 52 of 276 patients were examined by both MRI and CT. Of the 520 end plates, 93 end plates showed Modic changes, of which 34 end plates have shown sclerotic changes in CT images. 11.8% of 34 end plates have shown Modic Type I, 20.6% of 34 end plates have shown Modic Type II, 2.9% of 34 end plates have shown Modic Type III and 64.7% of 34 end plates have shown mixed Modic type. CONCLUSION: End plate oedema makes up the majority of mixed types especially Types I-II and Types II-I. The end plate sclerosis on CT images may not just mean Modic Type III but does exist in all types of Modic changes, especially in mixed Modic types, and may reflect vertebral body mineralization rather than change in the bone marrow. ADVANCES IN KNOWLEDGE: End plate oedema and end plate sclerosis are present in a large proportion of mixed types. PMID- 26828969 TI - Imaging of presacral masses--a multidisciplinary approach. AB - Our objective is to describe an approach for retrorectal/presacral mass evaluation on imaging with attention to imaging features, allowing for refinement of the differential diagnosis of these masses. Elaborate on clinically relevant features that may affect biopsy or surgical approach, of which the radiologist should be aware. A review of current literature regarding the diagnosis and treatment of retrorectal/presacral masses was performed with attention to specific findings, which may lend refinement to the differential diagnosis of these masses. Cases were obtained by searching through a radiology database at a single institution after Institutional Review Board approval. Recent advances in imaging and treatment methods have led to the increased role of radiology in both imaging and tissue diagnosis of retrorectal masses. Surgical philosophies surrounding the treatment of these masses have not significantly changed in recent years, but there are a few key factors of which the radiologist must be aware. The radiologist can offer refinement of the differential diagnosis of retrorectal masses and can elaborate on salient findings which could alter the need for neoadjuvant chemoradiation therapy, pre-surgical tissue diagnosis and surgical approach. This article presents an imaging approach to retrorectal/presacral masses with emphasis on findings which can dictate the ultimate need for neoadjuvant therapy and pre-surgical tissue diagnosis and alter the preferred surgical approach. This article consolidates key findings, so radiologists can become more clinically relevant in the evaluation of these masses. PMID- 26828970 TI - Clinical and imaging features of a subchondral insufficiency fracture of the femoral head after internal fixation of a femoral neck fracture: a comparison with those of post-traumatic osteonecrosis of the femoral head. AB - OBJECTIVE: Recent articles have demonstrated that subchondral insufficiency fractures (SIFs) of the femoral head can occur following internal fixation of femoral neck fractures (FNFs), in addition to post-traumatic osteonecrosis (ON) of the femoral head. The purpose of this study was to determine the clinical and imaging features of SIF after internal fixation of FNFs compared with those of post-traumatic ON. METHODS: We reviewed five hips in five patients, who received internal fixation for the treatment of FNF and were diagnosed as having SIF according to the shape of the low-intensity band on the T1 weighted MR image. Four hips of four patients with post-traumatic ON were compared with the SIF cases. Both the clinical and imaging findings were investigated. RESULTS: There were no significant differences in the age, sex, body mass index, stage of FNF or duration from injury to surgery between SIF and post-traumatic ON. Regarding the prognosis, one of the five cases (20%) with SIF underwent prosthetic replacement owing to a progressive collapse of the femoral head. Two of the four cases (50%) with post-traumatic ON underwent prosthetic replacement. CONCLUSION: The results of this study suggest that SIF should be considered a possible condition following the internal fixation of FNFs, and it is important to differentiate SIF from post-traumatic ON. ADVANCES IN KNOWLEDGE: SIF should be considered a possible condition following the internal fixation of FNFs. PMID- 26828971 TI - Comparison of treatment planning parameters for dose painting head and neck plans delivered with tomotherapy. AB - OBJECTIVE: The aim of this study was to determine which physical delivery parameter changes are most suitable for multiple-level dose-painting treatment plans with helical tomotherapy (HT). METHODS: A total of 96 treatment plans were generated for 12 patients who had undergone fluorine-18 fludeoxyglucose positron emission tomography/CT ((18)F-FDG-PET/CT) scan to plan head and neck cancer treatment. Based on these PET-CT images, the dose was escalated to 96 Gy in 32 fractions as a function of PET intensity values. The intensity-based prescription was converted into seven discrete dose levels. For the same patient, different HT plans were optimized by varying parameters such as field width (FW), pitch (PF) and modulation factor (MF). Dose conformity was evaluated using quality-volume histograms, quality factors (QFs), weighted index of achievement (IOAw), coldness (IOCw) and hotness (IOHw). Moreover, doses to organs at risk (OARs), target volumes and execution time were analyzed. RESULTS: Median QFs were the best for FW = 1.05 cm (QF = 2.10) and the worst for FW = 2.5 cm (QF = 3.04). The same trend was observed for IOAw, IOCw and IOHw. Combination of FW = 1.05 cm and MF = 5 leads to the longest beam-on time (above 25 min), whereas FW = 2.5 cm and MF = 3 lead to the shortest time (below 8 min). Data analyzed based on dose-volume histogram showed that changes in FW had the strongest impact on plan quality, whereas the effect of MF and PF changes was moderate. CONCLUSION: HT is suitable for multiple-level dose-painting treatment plans. ADVANCES IN KNOWLEDGE: Changes in FW and MF had the greatest impact on dose distribution quality and beam-on time. Changes in PF only influenced doses to the OARs. PMID- 26828972 TI - Radiation protection of the eye lens in medical workers--basis and impact of the ICRP recommendations. AB - The aim of this article was to explore the evidence for the revised European Union basic safety standard (BSS) radiation dose limits to the lens of the eye, in the context of medical occupational radiation exposures. Publications in the open literature have been reviewed in order to draw conclusions on the exposure profiles and doses received by medical radiation workers and to bring together the limited evidence for cataract development in medical occupationally exposed populations. The current status of relevant radiation-protection and monitoring practices and procedures is also considered. In conclusion, medical radiation workers do receive high doses in some circumstances, and thus working practices will be impacted by the new BSS. However, there is strong evidence to suggest that compliance with the new lower dose limits will be possible, although education and training of staff alongside effective use of personal protective equipment will be paramount. A number of suggested actions are given with the aim of assisting medical and associated radiation-protection professionals in understanding the requirements. PMID- 26828973 TI - Radiation dose awareness and disclosure practice in paediatric emergency medicine: how far have we come? AB - The past decade has brought increasing coverage in the medical literature and lay media of the potential association between low-level radiation from diagnostic imaging and an increased lifetime cancer risk. Both physician and public opinion increasingly favour a greater discussion of benefit and risk with patients and their families when such imaging is being considered. Particular attention has been directed towards CT, its use in children and the emergency department setting. We will review the evolution of radiation dose awareness and knowledge among emergency physicians (EPs) alongside the parallel increase in public awareness. We will then discuss expectations for risk disclosure and the challenges faced by EPs and radiologists as we strive to provide this in a clinically balanced and meaningful way. PMID- 26828974 TI - Oral pharmacotherapy for overactive bladder in older patients: mirabegron as a potential alternative to antimuscarinics. AB - OBJECTIVE: Overactive bladder (OAB) is a particular challenge to treat in older adults with co-morbid conditions taking multiple medications. Antimuscarinics (e.g., solifenacin, fesoterodine) and beta3-adrenergic receptor agonists (mirabegron) are similarly efficacious; however, antimuscarinics may be associated with side effects that result in poor persistence and contribute to anticholinergic burden, particularly in those taking other medications with anticholinergic properties. With a mechanism of action distinct from antimuscarinics, mirabegron has a different tolerability profile and does not contribute to anticholinergic burden. The objective of this review was to compare and contrast the tolerability profiles of antimuscarinics and mirabegron in older patients to inform practice. METHODS: Prospective trials or retrospective subgroup analyses of antimuscarinics for the treatment of OAB in older patients were identified through a search of PubMed. Tolerability data and results of subgroup analyses of mirabegron in patients aged >=65 and >=75 years from a pooled analysis of three trials each of 12 weeks and a 1 year trial are described. RESULTS: Anticholinergic adverse events (AEs) including dry mouth and constipation were more frequent with antimuscarinics versus mirabegron. In patients aged >=65 years, dry mouth occurred with a six-fold higher incidence with tolterodine extended-release (ER) 4 mg than with mirabegron 25 mg or 50 mg over 12 weeks, and a three-fold higher incidence with tolterodine ER than mirabegron 50 mg over 1 year. Mirabegron had a low incidence of central nervous system effects. A systematic review of the cardiovascular safety profile of mirabegron has not identified any clinically significant effects on blood pressure or pulse rate at therapeutic doses amongst patients aged >=65 years. CONCLUSIONS: Mirabegron has a more favorable tolerability profile than antimuscarinics amongst older patients and may provide an improved benefit-to risk ratio and therefore be considered as an alternative to antimuscarinics for older patients. PMID- 26828976 TI - Who was the Red Dean? PMID- 26828975 TI - Mobilization of lymphatic endothelial precursor cells and lymphatic neovascularization in primary Sjogren's syndrome. AB - Although lymphatic neovascularization may be a key feature of chronic inflammation, it is almost unexplored in primary Sjogren's syndrome (pSS). A recent study revealed a pro-lymphangiogenic function of interleukin (IL)-17, a leading player in pSS pathogenesis. The aims of the study were to investigate lymphangiogenic mediators and lymphatic vasculature in pSS, as well as their possible association with IL-17. Circulating lymphatic endothelial precursor cells (LEPCs) and Th17 cells were enumerated in pSS patients and healthy donors. VEGF-C and IL-17 levels were assessed in paired serum samples. Lymphatic vasculature, VEGF-C/VEGF receptor (VEGFR)-3 and IL-17 were evaluated in pSS minor salivary glands (MSGs) and compared with normal and non-specific chronic sialadenitis (NSCS) MSGs. Circulating LEPCs were expanded in pSS and correlated with circulating Th17 cells, IL-17 and VEGF-C. In pSS MSGs, a newly formed lymphatic capillary network was found within periductal inflammatory infiltrates and the number of interlobular lymphatic vessels was significantly increased compared with normal and NSCS MSGs. Strong VEGF-C expression was detected in pSS ductal epithelial cells and periductal inflammatory cells. Numerous VEGFR-3(+) infiltrating mononuclear cells were exclusively observed in pSS MSGs. VEGFR-3 expression was strongly increased in lymphatic capillaries of pSS MSGs. IL-17(+) inflammatory cells were preferentially observed around lymphatic vessels in pSS MSGs. This study supports the notion that lymphvasculogenesis and lymphangiogenesis are active in pSS, thereby unmasking a novel aspect of disease pathogenesis. In addition, our results suggest another possible pathogenic role of IL-17 in pSS, further supporting its therapeutic targeting in this disease. PMID- 26828977 TI - PTSD symptom course during the first year of college. AB - OBJECTIVES: In this study we examined patterns of transition in posttraumatic stress disorder (PTSD) symptoms over the 1st year of college. We also examined 2 factors that might predict these transitions: trauma exposure and alcohol involvement. METHOD: Matriculating students (N = 944; 65% female) completed assessments of PTSD, trauma exposure, and alcohol use and consequences multiple times in their freshman year. Three symptom classes (no symptoms, moderate symptoms, and severe symptoms) were identified. Examination of transitions from 1 status to another was conducted with latent transition analysis. RESULTS: These models revealed considerable variability in the course of PTSD symptoms. The most common pattern was resolution, yet a significant portion of students showed other patterns. Symptom worsening was more commonly observed in the 2nd semester. Trauma exposure had a deleterious effect on PTSD symptom change trajectories, as did alcohol involvement, though less consistently so. CONCLUSIONS: Interventions that focus on the timing and correlates of symptom progression may benefit college students with posttraumatic distress. (PsycINFO Database Record PMID- 26828979 TI - Association between Helicobacter pylori hopQI genotypes and human gastric cancer risk. AB - The Helicobacter pylori use a number of mechanisms to survive in the stomach lumen and can lead to gastritis and reduction in stomach acid secretion. It has been found that the risk of developing gastric carcinoma is associated to heterogeneity of H. pylori virulence factors such as HopQ. The HopQ is one of the outer membrane proteins involved in bacterial adherence to gastric mucosa and has been suggested to also main role in the virulence of H. pylori. The purpose of the current study was to investigate the association between different H. pylori virulence hopQI (types I) genotyping and patients with gastroduodenal disorders. For this purpose 58 stomach biopsies of the patients with gastric cancer and 100 saliva samples from healthy and H. pylori infected individuals were collected and studied. Then genomic DNA was purified and PCR was done for desired gene via specific primers. The H. pylori infections were diagnosed using PCR for GlmM gene. Then frequencies of hopQI+ and hopQI- genotypes were determined in H. pylori infected cases. Statistical analysis showed that there were not significant differences between healthy and diseased ones for genotypes hopQI+ and hopQI-. Then the hopQI+ cannot be as a risk factor genotype for gastric cancer. PMID- 26828978 TI - Protective effect of Honokiol against endometriosis in Rats via attenuating Survivin and Bcl-2: A mechanistic study. AB - Nearly 10-15% of women in the reproductive age were affected by endometriosis and currently facing the unmet need of effective therapeutic interventions for its management. Concerning this, the present study was intended to investigate the effect of Honokiol (HK) for the treatment of endometrial hyperplasia. The rat endometrial model was established and subsequently administered with a numerous dose of HK. The histopathology of tissues was also investigated. Results showed that, HK effectively inhibit the proliferation of rat edometeriotic tissues in a dose dependent manner. In terminal deoxynucleotidyl transferase (TdT) -mediated dUTP biotin nick end labeling (TUNEL) method, HK was able to bring apoptosis in endometrotic cells. Moreover, it also inhibits the mRNA levels of Survivin gene and Bcl-2 (B-cell lymphoma 2) in qPCR and Western blot analysis together with increases the mRNA level of apoptosis promoting factor Bax. These results clearly suggest that, HK was proficient to provoke apoptosis of rat endometriotic cells. PMID- 26828980 TI - YiQi ChuTan Recipe Inhibits Epithelial Mesenchymal Transition of A549 Cells under Hypoxia. AB - This study aims to investigate mechanism of YiQi ChuTan Recipe (YCR) for inhibiting epithelial mesenchymal transition (EMT) of A549 cells under hypoxia. Flow cytometry was used to optimize YCR dosage by measuring A549 apoptosis, which were subjected to different treatments, including normal condition, hypoxia, hypoxia+YCR. Cell morphology and expression of EMT were measured with differential interference contrast microscopy, real-time PCR and western blot. Optimized condition of 4 mg/ml YCR and 2% O2 for 72 h was used to establish hypoxia. Under hypoxic condition, morphology of A549 cells changed from oblate fusi-form to elongated spindle. E-cadherin expression decreased while vimentin and fibronectin increased. EMT-related genes expression were significantly increased in hypoxia group compared to control group (P<0.05). After treatment with YCR, mesenchymal cells obviously decreased and EMT-related genes expression was significantly decreased (P<0.05). Changes of E-cadherin, vimentin and fibronection were significantly attenuated by YCR when compared to hypoxia group. Expression of proteins GRP78, SRC, MAPK, smad2/3 were significantly increased in hypoxia group compared to control group, but was significantly inhibited by YCR treatment. In conclusion, A549 cells underwent EMT under hypoxia while YCR reversed the EMT through GRP78, smad2/3 and SRC/MAPK signal pathway. PMID- 26828981 TI - DNA Methylation and microRNA patterns are in association with the expression of BRCA1 in ovarian cancer. AB - Ovarian cancer is the sixth most prevalent cancer in women and is considered the most lethal gynecological malignancy. It can be inherited as a familial disease but also has a strong spontaneous occurrence. Although the disease is associated with genome instability brought on by genetics and environmental factors there is evidence that mutations in the gene encoding for the breast cancer type 1 susceptibility protein (BRCA1) or its down-regulation are involved in its development. Down-regulation of BRCA1 expression by hypermethylation of its promoter may account for some cases of ovarian cancer but this does not explain the cause of the majority of the disease. This review explores the role of BRCA1 promoter hypermethylation and micro-RNAs (miRNA) involved in the regulation of BRCA1 and their role in ovarian cancer development as well as some of the exciting discoveries which could lead to targeting miRNA with a view to restoring BRCA1 expression in diseased tissues. PMID- 26828982 TI - Angiotensin II up-regulates monocarboxylate transporters expression in the rat adrenal gland. AB - Angiotensin II (Ang II) is a major regulator of aldosterone secretion in the adrenal zona glomerulosa because it up-regulates the expression of a large number of genes involved in aldosterone biosynthesis. The transport of acetate across adrenocortical cells is a crucial step in the de novo synthesis of cholesterol, the steroid precursor of aldosterone. However, whether Ang II can affect this transport remains unknown. The current study aims to investigate the effect of in vivo infusion of Ang II on monocarboxylate transporters (MCT1, MCT2, and MCT4) gene expression in the rat adrenal gland. Immunohistochemical analysis and real time PCR were used to examine the expression of MCTs at the protein and mRNA levels, respectively. The immunohistochemical analysis showed that higher numbers of cells expressed MCT1, MCT2, and MCT4 proteins in the zona glomerulosa and zona fasiculata of the adrenal cortex of Ang II-infused rats. Furthermore, real-time PCR indicated that in vivo infusion of Ang II increased the mRNA levels of MCT1, MCT2, and MCT4 in the rat adrenal gland. MCT up-regulation might maximize the intracellular transport of acetate in response to the stimulatory effect of Ang II on aldosterone secretion by the adrenal zona glomerulosa.. PMID- 26828983 TI - Losartan sensitizes selectively prostate cancer cell to ionizing radiation. AB - Losartan is an angiotensin II receptor (AT-II-R) blocker that is widely used by human for blood pressure regulation. Also, it has antitumor property. In this study, we investigated the radiosensitizing effect of losartan on cellular toxicity induced by ionizing radiation on prostate cancer and non-malignant fibroblast cells. Human prostate cancer (DU-145) and human non-malignant fibroblast cells (HFFF2) were treated with losartan at different concentrations (0.5, 1, 10, 50 and 100 uM) and then these cells were exposed to ionizing radiation. The cell proliferation was determined using MTT assay. Our results showed that losartan exhibited antitumor effect on prostate cancer cells; it was reduced cell survival to 66% at concentration 1 uM. Losartan showed an additive killing effect in combination with ionizing radiation on prostate cancer cell. The cell proliferation was reduced to 54% in the prostate cancer cells treated with losartan at concentration 1 uM in combination with ionizing radiation. Losartan did not exhibit any toxicity on HFFF2 cell. This result shows a promising effect of losartan on enhancement of therapeutic effect of ionizing radiation in patients during therapy. PMID- 26828984 TI - The E-selectin S149R polymorphisms in breast cancer in a northern Iran population. AB - Breast cancer is a complex polygenic disorder that genetic factors play an important role in disease etiology. E-selectin mediates the adhesion of tumor cells to endothelial cells. This interaction is associated with metastatic dissemination. Expression of E-selectin on the endothelium is a hallmark of inflammation. This study was performed to evaluate the association of E-selectin S149R polymorphisms and the risk of breast cancer. A total of 100 patients with breast cancer and 120 healthy sample donors (controls) were recruited in this study. Genomic DNA was extracted from fresh blood samples and genotyping of the E selectin genes was performed using PCR-restriction fragment length polymorphism (PCR-RFLP). The frequencies of the CC, AC and AA genotypes were 2%, 84%, and 14% in patients and 2%, 12%, and 86% in controls, respectively, while the A and C allelic frequency was 56%, 44% in patients and 92%, 8% in controls, respectively. Statistical analysis showed that there is a significant difference between two groups (P<0.0001). It is concluded that the E-selectin S149R polymorphisms is associated with the oncogenesis of breast cancer in a population in northern Iran. PMID- 26828985 TI - Cell-based evaluation of a novel Dictyophora indusiata polysaccharide against oxidative-induced erythrocyte hemolysis. AB - The protective effect of a polysaccharide from Dictyophora indusiata(DP1)against oxidative hemolysis was comprehensively evaluated. The 2, 2-azobis (2-amidino propane) dihydrochloride (AAPH)-induced erythrocyte hemolysis assay showed that DP1 exhibited excellent anti-hemolytic activity(87.4% hemolysis suppression ratio at 20 nmol/mL). Also, the formation of conjugated diene induced by cupric chloride (CuCl2) in plasma was significantly inhibited by DP1. Besides, DP1 could effectively inhibit AAPH-induced overproduction of reactive oxygen species (81.5% inhibition at 20 nmol/mL) and alleviated the enhancement of intracellular antioxidant enzymes including superoxide dismutase(SOD), glutathione peroxidase (GPX) and catalase (CAT) activities. Also, the malondialdehyde (MDA) formation caused by oxidative stress was suppressed by 57.0% at DP1 concentration of 20 nmol/mL. Taken together, the possible intracellular antioxidant detoxifying mechanism of DP1 was probably via preserving the activities of the antioxidant enzymes (SOD, GPx and CAT) as well as inhibiting lipid peroxidation, and thus alleviated erythrocytes oxidation and plasma oxidation. PMID- 26828986 TI - Signaling lansdscape of prostate cancer. AB - Research over the decades has gradually and sequentially shown that both intratumor heterogeneity and multifocality make prostate cancer difficult to target. Different challenges associated with generation of risk-stratification tools that correlate genomic landscape with clinical outcomes severely influence clinical efficacy of therapeutic strategies. Androgen receptor mediated signaling has gained great appreciation and rewiring of AR induced signaling cascade in absence of androgen, structural variants of AR have provided near complete resolution of genomic landscape and underlying mechanisms of prostate cancer. In this review we have attempted to provide an overview of most recent advancements in our knowledge related to different signaling cascades including TGF, SHH, Notch, JAK-STAT in prostate cancer progression and development. PMID- 26828987 TI - Effects of genetic factors to stent thrombosis due to clopidogrel resistance after coronary stent placement. AB - Stent thrombosis (ST) is considered as a multifactorial problem which is mostly occurs due to clopidogrel resistance. It may be due to some CYP450 enzyme deficiencies which play role in clopidogrel metabolism. Therefore the aim of this study is to detect the mutations in CYP2C19 and CYP2C9 genes which may cause ST, and to investigate the relation between other risk factors and ST. 50 individuals who have stent thrombosis and 50 individuals who haven't got any complication were enrolled as patient and control group respectively. *2,*3,*4,*5,*17 mutations in CYP2C19 gene and *2 ve *3 mutations in CYP2C9 gene were investigated with RT-PCR. Clopidogrel and aspirin resistance were investigated with multiple electrode platelet aggregometry. Results were evaluated statistically. CYP2C19*2 mutation was found statistically higher in patients (% 18), whereas CYP2C19*17 was found statistically higher in controls (% 36)(p<0.05). Additionally, it was found that patients who have clopidogrel and/or aspirin resistance also have CYP2C19*1/*2 or CYPC19*2/*2 genotype. These relations were also found statistically significant. (p=0,000005 for clopidogrel resistance and p=0,000059 for aspirin resistance). In conclusion, it was suggested that there is a relation between CYP2C19*2 mutations and ST due to clopidogrel resistance, and CYP2C19*17 may have a protective role in this process. The use of novel and more potent drug or high clopidogrel maintenance dosing before stent implantation may be beneficial treatment options for antiplatelet therapy in CYP2C19*2 carriers. PMID- 26828988 TI - RT-PCR detection of exotoxin genes expression in multidrug resistant Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa (PA) is an opportunistic pathogen responsible for causing a wide variety of acute and chronic infections with significant levels of morbidity and mortality. These infections are very hard to eradicate because of the expression of numerous virulence factors and the intrinsic resistance against antibiotics. Herein, this study analyzed antimicrobial susceptibility of PA isolated from broiler chickens and cattle as well as expression of five significant exotoxin genes (exoU, exoS, toxA, lasB, and phzM) and ecfX as internal control. Genomic DNA was amplified employing oprL gene for species specific detection of PA. The highest resistance was found to ampicillin, erythromycin, followed by, chloramphenicol, trimethoprim/ sulfamethoxazole and tetracycline, intermediately sensitive to ceftazidime, cefoperazone, and highly sensitive to gentamicin, levofloxacin, imipenem, ciprofloxacin and colistin. It appears that exoU+ and increased resistance to SXT may be co-selected traits. Vast majority of PA isolates expressed exoS (78.6%), exoU (71.4%) and both in more virulent strains. The ubiquity of toxA, lasB, exoU and exoS among PA clinical isolates is consistent with an important role for these virulence factors in chicken respiratory diseases and cattle mastitis that can be highlighted as potential therapeutic targets for treatment of infections caused by heterogeneous and resistant PA strains. PMID- 26828989 TI - All-trans retinoic acid inhibits HOXA7 expression in leukemia cell NB4. AB - Leukemia is a malignant proliferative disease of blood system, which is caused by hyperplasia of white blood cells and infiltration into other tissues and organs with blood flow, leading to a series of clinical manifestations. In this study, we detected the expression of HOXA7 gene in human acute promyelocytic leukemia cell line NB4. The expression level of HOXA7 decreased in the presence of ATRA, which was able to inhibit the proliferation of NB4 cells. Furthermore, ATRA altered the morphology of NB4 cells. The study suggested that HOXA7 might be a new gene candidate that influences the maturation of acute myeloid leukemia, and provided the molecular basis for the treatment for acute promyelocyticleukemia. PMID- 26828990 TI - Hypo/unmethylated promoter status of Cdk2 gene correlates with its over expression in ovarian cancer in north Indian population. AB - Cdk2 has been seen to play crucial roles in cell cycle regulation particularly in G1 to S phase transition and it is known to be involved in cancer progression and cancer cell proliferation. The aim of this study was to evaluate (i) the expression of cdk2 in malignancy of ovarian tumors and (ii) correlation between expression and DNA methylation. Clonal bisulfite sequencing and quantitative PCR analysis was performed for promoter methylation and expression analysis respectively in normal and ovarian tumor tissues. Increased methylation level was observed in normal ovarian tissues than ovarian carcinoma. An inverse relationship was found with expression levels of Cdk2 and DNA methylation. PMID- 26828991 TI - Concentration analysis of hypoxi-inducible factor-1alpha; and vascular endothelial growth factor in patients with aortic aneurysm at different stages and its clinical significance. AB - This study aims to investigate serum concentration of hypoxia inducible factor 1alpha; (HIF-1alpha) and vascular endothelial growth factor (VEGF) in patients with aneurysms at different stages, and to determine critical role in early diagnosis and evaluation of severity. A cohort of 102 cases of patients diagnosed as aneurysms during May 2012 to April 2015 in our hospital were retrospectively analyzed. Patients were divided into early stage group (n=32), mid-term group (n=34), and late stage group (n=36) according to severity of aneurysms. The measurement of concentration of HIF-1alpha and VEGF was detected by Enzyme-linked immunosorbent assays (ELISA). Serum level of HIF-1alpha; and VEGF was compared among different groups. The results showed that serum concentrations of HIF 1alpha (t=25.53, P<0.05) and VEGF (t=12.10, P<0.05) in early stage group were significantly higher than those in normal group. Serum concentrations of HIF 1alpha (t=25.63, P<0.05) and VEGF (t=9.71, P<0.05) in the mid-term group were significantly higher than those in the early stage group. Serum concentrations of HIF-1alpha (t=14.61, P<0.05) and VEGF (t=21.42, P<0.05) in the late stage group were significantly higher than those in the mid-term group. In conclusion, serum HIF-1alpha and VEGF has clinical value of early diagnosis and assessment of disease severity. PMID- 26828992 TI - Increase in oxidative stress and mitochondrial impairment in hypothalamus of streptozotocin treated diabetic rat: Antioxidative effect of Withania somnifera. AB - Hypothalamus, the primary brain region for glucose sensing, is severely affected by oxidative stress in diabetes mellitus. Oxidative stress in this region of brain may cause severe impairment in neuronal metabolic functions. Mitochondria are prominent targets of oxidative stress and the combination of increased oxidative stress and mitochondrial dysfunctions may further decline hypothalamic neuronal functions. In the present study we examined the oxidative damage response, antioxidative responses and mitochondrial membrane permeability transition in hypothalamus of streptozotocin-treated diabetic rats. Our results show that streptozotocin significantly increases hypothalamic lipid peroxidation, protein carbonyl content while glutathione peroxidase and reduced glutathione were declined. Mitochondrial impairment marked by an increase in mitochondrial membrane permeabilization was seen following streptozotocin treatment in the hypothalamus. The oral administration of Withania somnifera root extract stabilized mitochondrial functions and prevented oxidative damage in the hypothalamus of diabetic rat. These findings suggest an increase in the oxidative stress and decline in antioxidative responses in the hypothalamus of streptozotocin treated diabetic rats. Withania somnifera root extract was found useful in reducing oxidative stress and mitochondrial impairment in hypothalamus of diabetic rat. PMID- 26828993 TI - Histamine H4 Receptor mediates interleukin-8 and TNF-alpha release in human mast cells via multiple signaling pathways. AB - Histamine, mainly produced by mast cells, is an important inflammatory mediator in immune response. Recently Histamine H4 Receptor (H4R) was also identified in mast cells, from which pro-inflammatory cytokines and chemokines are released. However, the mechanism of how H4R mediates these cytokines and chemokines release in mast cells was still unclear. To further explore the role of H4R in the immune inflammatory response in mast cells, we tested the release of inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), chemokine interleukin-8 (IL-8) and the relevant signaling pathways activated by H4R on LAD2 cells (a human mast cell line). We found that the release of IL-8 and TNF-alpha were blocked by inhibitors of PI3K, ERK and Ca2+-Calcineurin-NFAT signaling pathways, while the release of these cytokines and chemokines were enhanced by the inhibitor of P38 signaling pathway. However, inhibitors of the JNK and NF-kappaB signaling pathways had little effect on the expression of the pro-inflammatory mediators. Moreover, activation of the H4R could induce phosphorylation of ERK, p38 and AKT in mast cells. In conclusion, we found that H4R mediates the release of inflammatory cytokine TNF-alpha and chemokine IL-8 in human mast cells via PI3K, Ca2+-Calcineurin-NFAT and MAPKs signaling pathways. PMID- 26828994 TI - The synergistic effect of omega3 and Vit D3 on glycemia and TNF-alpha in islet transplantation. AB - The current treatment of type 1 diabetes consists of insulin administration. Transplantation of islets of Langerhans is considered very favorable because the full effect of insulin treatment cannot be obtained in severe cases. Although agents such as omega-3 (omega3) and vitamin D3 (Vit D3) are known to contribute to the success of islet allo-transplantation (ITX), in this study we aimed to experimentally determine their effects on glycemia and TNF-alpha production. Wistar albino rats, which were used as recipients, were given omega3, Vit D3, and islets by gavage, and intraperitoneal- and intraportal injections, respectively. Daclizumab (DAC) was used for immunosuppression. Glycemia levels decreased in rats treated with omega3 and vit D3. TNF-alpha increased in all groups due to application of STZ. After ITX (day +1), the weakest increase was observed in the omega3 + Vit D3 group. In the ITX+DAC group, compared with that of ITX only, DAC was shown to decrease levels of TNF- alpha following ITX, only in control group, however, similar levels of TNF-alpha were observed in other groups. The values in the treated groups were already lower than those of the controls in the ITX group and also remained almost equal in the ITX+DAC group. We suggest that the use of omega3 and Vit D3 together will improve the pro-inflammatory aspect encountered during and after ITXs, and contribute to the reduction of the dose of immunosuppressants in these procedures. PMID- 26828995 TI - Dicliptera Chinensis polysaccharides target TGF-beta/Smad pathway and inhibit stellate cells activation in rats with dimethylnitrosamine-induced hepatic fibrosis. AB - This study aims to study impact of Dicliptera chinensis polysaccharide (DCP) on hepatic fibrosis (HF) and activation of hepatic stellate cells (HSCs). Liver fibrosis model was induced by intraperitoneal injection of dimethyl nitrosamines (DMN) in rat. Rats in treatment group were administrated with different concentrations of DCP (0, 100, 300 mg/kg) by intraperitoneal injection. Hematoxylin and eosin (H&E) and Masson's trichrome staining were used to assess histo-pathological change. alpha-SMA, TGF-beta1 and pSmad 2/3 were assayed by immuno-histochemistry. HSC-T6 cells were stimulated by recombined rat TGF-beta1 (1 ng/mL) to simulate an activating model in vitro and then interfered with DCP (concentration of 0, 25, 50, 100, 200, 400 ug/ml). MTT assay was used to determine cell proliferation and western blotting was used to detect alpha-SMA and pSmad 2/3 expression. Results demonstrated that DCP alleviated DMN-induced liver fibrosis in rat and significantly down-regulated TGF-beta1 expression, pSmad2/3 and alpha-SMA in liver tissue in a dose-dependent way. DCP inhibited proliferation and activation of TGF-beta1-stimulated HSC-T6 in vitro and significantly down-regulated alpha-SMA and pSmad2/3 expression. In conclusion, this study revealed that DCP attenuates progression of liver fibrosis through suppressing TGF-beta/Smad pathway. DCP is a potential botanical polysaccharide to management liver fibrosis. PMID- 26828996 TI - CXCL9 expression and polyomavirus BK infectivity in renal transplant patients with nephropathy. AB - Polyomavirus BK is an important risk factor for nephropathy and renal lose after kidney transplantation. CXCL9 is a key immunoregulatory molecule which participates in stimulation and migration of immune cells to the infected sites. Thus, the main aim of this study was to evaluate the expression levels of CXCL9 mRNA and serum levels in the infected polyomavirus BK infected renal transplant patients with and without nephropathy compared with healthy controls. This cross sectional study was performed on three studied groups including: polyomavirus BK infected vs. non-infected renal transplant patients with nephropathy and healthy controls. The mRNA and serum levels of CXCL9 were evaluated on the studied patient and control samples using an in-house comparative real time PCR and ELISA methods, respectively. The mRNA expression and serum levels of CXCL9 were both increased in polyomavirus BK infected compared with non-infected renal transplant patients and also in comparing with healthy controls. This upregulation was significant in the serum level in polyomavirus BK infected vs. non-infected patients and also in comparing with controls. According to these results, polyomavirus BK can induce renal complications via stimulation of inflammatory biomarkers like chemokine. Confirmation of the increasing of the expression and production of CXCL9 as a pro-inflammatory chemokine in renal transplanted polyomavirus BK infected patients with nephropathy need to confirm in further completed studies with longer follow-up. PMID- 26828997 TI - Protective effect of ferulic acid against 2,2'-azobis(2-amidinopropane) dihydrochloride-induced oxidative stress in PC12 cells. AB - Oxidative stress is closely related to the pathogenesis of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. However, the underlying antioxidant mechanisms of ferulic acid (FA) aganist oxidantive stress are poorly understood. We evaluated the potential protective effects of FA against 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced damage in PC12 cells. Our results indicated that pretreatment with FA prior to AAPH exposure significantly increased PC12 cell survival, and also increased catalase and superoxide dismutase activity. Furthermore, FA treatment reduced cellular lactate dehydrogenase release and malondialdehyde levels. It attenuated AAPH induced apoptosis in PC12 cells, as determined by flow cytometric detection of annexin V. Reductions in mitochondrial membrane potential and accumulation of intracellular Ca2+ were also inhibited by FA treatment. These findings suggested that FA protected PC12 cells against AAPH-induced oxidative stress, and may be a neuroprotective agent. PMID- 26828998 TI - Parenting Coordination: Applying Clinical Thinking to the Management and Resolution of Post-Divorce Conflict. AB - There is a small but significant number of parents who remain stuck in a high level of conflict with each other after the legal conclusion of their divorce. Exposure to chronically high levels of parental conflict is a strong risk factor negatively affecting both children's short- and long-term adjustment. Parenting coordination is a nonadversarial, child-focused dispute-resolution process designed to help divorced parents contain their conflict to protect children from its negative effect. Parenting coordination is a hybrid role combining different skills and conflict-resolution approaches. In high-conflict divorce, each parent's internalization of relationship patterns constructed from past experiences contributes to the intractable nature of the interparent conflict. A case presentation illustrates how this clinical perspective enhances the parenting coordinator's ability to work with parents to manage and contain their parenting conflicts with each other. PMID- 26828999 TI - Metasurface Broadband Solar Absorber. AB - We demonstrate a broadband, polarization independent, wide-angle absorber based on a metallic metasurface architecture, which accomplishes greater than 90% absorptance in the visible and near-infrared range of the solar spectrum, and exhibits low absorptivity (emissivity) at mid- and far-infrared wavelengths. The complex unit cell of the metasurface solar absorber consists of eight pairs of gold nano-resonators that are separated from a gold ground plane by a thin silicon dioxide spacer. Our experimental measurements reveal high-performance absorption over a wide range of incidence angles for both s- and p-polarizations. We also investigate numerically the frequency-dependent field and current distributions to elucidate how the absorption occurs within the metasurface structure. PMID- 26829000 TI - Randomized Controlled Trial of Exercise for ADHD and Disruptive Behavior Disorders. AB - PURPOSE: The objective of this study is to test the feasibility and impact of a 10-wk after-school exercise program for children with attention deficit hyperactivity disorder and/or disruptive behavior disorders living in an urban poor community. METHODS: Children were randomized to an exercise program (n = 19) or a comparable but sedentary attention control program (n = 16). Cognitive and behavioral outcomes were collected pre-/posttest. Intent-to-treat mixed models tested group-time and group-time-attendance interactions. Effect sizes were calculated within and between groups. RESULTS: Feasibility was evidenced by 86% retention, 60% attendance, and average 75% maximum HR. Group-time results were null on the primary outcome, parent-reported executive function. Among secondary outcomes, between-group effect sizes favored exercise on hyperactive symptoms (d = 0.47) and verbal working memory (d = 0.26), and controls on visuospatial working memory (d = -0.21) and oppositional defiant symptoms (d = -0.37). In each group, within-group effect sizes were moderate to large on most outcomes (d = 0.67 to 1.60). A group-time-attendance interaction emerged on visuospatial working memory (F[1,33] = 7.42, P < 0.05), such that attendance to the control program was related to greater improvements (r = 0.72, P < 0.01), whereas attendance to the exercise program was not (r = 0.25, P = 0.34). CONCLUSIONS: Although between-group findings on the primary outcome, parent-reported executive function, were null, between-group effect sizes on hyperactivity and visuospatial working memory may reflect adaptations to the specific challenges presented by distinct formats. Both groups demonstrated substantial within-group improvements on clinically relevant outcomes. Findings underscore the importance of programmatic features, such as routines, engaging activities, behavior management strategies, and adult attention, and highlight the potential for after-school programs to benefit children with attention deficit hyperactivity disorder and disruptive behavior disorder living in urban poverty where health needs are high and services resources few. PMID- 26829001 TI - Concussive Injuries in Rugby 7s: An American Experience and Current Review. AB - PURPOSE: There is a comparative lack of concussion incidence data on the new Olympic sport Rugby 7s. This study aimed to determine the incidence (number of concussions per 1000 playing hours [ph]), mean and median severity (days absence), and cause of concussive injuries. METHODS: This is a prospective epidemiology study, amateur to elite/national candidate, male (9768) and female (3876) players in USA Rugby sanctioned tournaments, compliant with the international consensus statement for studies in rugby union. RESULTS: Concussions in US Rugby 7s were 7.7/1000 ph (n = 67). Women encountered concussions at 8.1/1000 ph, and men at 7.6/1000 ph (risk ratio [RR] = 1.10, P = 0.593). Elite/national-level players encountered concussions at higher rates (18.3/1000 ph) than lower levels (6.4/1000 ph; RR = 5.48, P < 0.001). Nonelite backs had higher concussive injury rates compared with forwards (7.7/1000 ph; 3.6/1000 ph; RR = 1.28, P = 0.024). Women missed 36.7 d absence from play, meanwhile men missed 27.9 d (P = 0.245). Retrospective history recall reflected previous concussive injuries occurred in 43% of the current study's cohort; of these, 57% encountered multiple concussions within 1 yr. The incidence of repetitive concussions was not statistically different between genders (RR = 1.09, P = 0.754). Most concussions occurred from tackles (63%) and collisions (24%) (P = 0.056). CONCLUSIONS: Sports-related concussions occurred with frequency among US amateur Rugby 7s players. US Elite tournament players sustained concussions at much higher rates than international male Rugby 7s counterparts. A substantial portion of US players who sustained a concussion had previous concussion injuries. Given the high rate of concussion, including repetitive concussive injuries, US Rugby 7s may benefit from concussion prevention measures similar to other contact sports such as instruction on proper tackling techniques, in-game and postgame medical assessment, and a standardized return-to-play protocol. PMID- 26829002 TI - Trauma, Technology, and Routine Outcome Measures. PMID- 26829003 TI - Influence of Family Smoking Habits and Passive Smoking on Smoking Status Among Belgrade University Students. AB - BACKGROUND: There are many factors that affect smoking behavior. OBJECTIVE: The aim of our study was to identify the most important risk factors related to smoking in the sample population of students at the University of Belgrade with a special emphasize on the family role. METHODS: The cross-sectional study was conducted in a population of 2,000 students of the Belgrade University. Four faculties (Medicine, Geography, Economics, and Electrical Engineering) from which the students participating in this research were chosen by the method of random choice, conducted in the period April-June 2010. RESULTS: Independent risk factors for smoking in students, assessed by multivariate logistic regression analysis, included: repeating a year (odds ratio (OR) = 1.67, p < .001), the number of hours spent in the rooms where others smoke (OR = 2.86, p < .001), brother smoker (OR = 1.88, p < .001), sister smoker (OR = 2.33, p < .001), knowledge about the association between smoking and lung cancer (OR = 0.31, p < .001), and depression (OR = 1.02, p = .013). CONCLUSION: Bearing in mind the influence of siblings, prevention, and intervention efforts should be focused more on family members than on the broader social environment. The results also indicate the need to develop a conscience on a healthy life style and to educate people to enhance and improve their health control. PMID- 26829004 TI - Identification and comparative analysis of the oriental river prawn (Macrobrachium nipponense) microRNA expression profile during hypoxia using a deep sequencing approach. AB - Hypoxia refers to a state of oxygen deficiency, which is observed frequently in aquaculture ponds. MicroRNAs (miRNAs) are small non-coding RNAs that are important effectors in regulating gene expression through posttranscriptional mechanisms. They are key elements in the response to hypoxia. The oriental river prawn (Macrobrachium nipponense) is an important commercial aquaculture species, and is sensitive to hypoxia. To date, there are no reports describing M. nipponense miRNAs. In this study, Solexa deep sequencing technology was used for high-throughput analysis of miRNAs in a small RNA library isolated from four M. nipponense tissues (gill, hepatopancreas, muscle and hemocytes). In total, 9,227,356 reads were obtained, 4,293,155 of which were related to 267 unique miRNAs, including 203 conserved and 64 prawn-specific miRNAs. Furthermore, miRNA features including length distribution and end variations were characterized. Annotation of targets revealed a broad range of biological processes and signal transduction pathways regulated by M. nipponense miRNAs. In addition, 880 co expressed and 39 specific (25 normoxia-specific and 14 hypoxia-specific) miRNAs that may be involved in the response to hypoxia were confirmed using miRNA microarray analysis from the four prawn tissues combined. Real-time quantitative PCR (qPCR) analysis of eight miRNAs in the normoxia and hypoxia groups showed good concordance between the sequencing and qPCR data. This study provides the first large-scale identification and characterization of M. nipponense miRNAs and their potential targets, and represents a foundation for further characterization of their roles in the regulation of the diversity of hypoxia processes. PMID- 26829005 TI - The "Profiles" document: a modern revision of the objectives of undergraduate medical studies in Switzerland. AB - The Joint Commission of the Swiss Medical Schools (SMIFK/CIMS) decided in 2000 to establish a Swiss Catalogue of Learning Objectives (SCLO) for undergraduate medical training, which was adapted from a similar Dutch blueprint. A second version of the SCLO was developed and launched in 2008. The catalogue is a prerequisite for the accreditation of the curricula of the six Swiss medical faculties and defines the contents of the Federal Licensing Examination (FLE). Given the evolution of the field of medicine and of medical education, the SMIFK/CIMS has decided to embark on a total revision of the SCLO. This article presents the proposed structure and content of Profiles, a new document which, in the future, will direct the format of undergraduate studies and of the FLE. Profiles stands for the Principal Relevant Objectives for Integrative Learning and Education in Switzerland. It is currently being developed by a group of experts from the six Swiss faculties as well as representatives of other institutions involved in these developments. The foundations of Profiles are grounded in the evolution of medical practice and of public health and are based on up-to-date teaching concepts, such as EPAs (entrustable professional activities). An introduction will cover the concepts and a tutorial will be displayed. Three main chapters will provide a description of the seven 2015 CanMEDS roles, a list of core EPAs and a series of ~250 situations embracing the most frequent and current conditions affecting health. As Profiles is still a work in progress, it is hoped that this paper will attract the interest of all individuals involved in the training of medical students. PMID- 26829007 TI - Food policy in the Canadian North: Is there a role for country food markets? AB - Food insecurity is widely reported to be at a crisis level in the Inuit territory of Nunavut, Canada. Various policies, programs, and initiatives have been proposed to tackle the problem, with increasing interest in developing a system of country food markets (CFMs) similar to Greenland. We examine if CFMs offer a feasible, sustainable, and effective model for strengthening food systems in Nunavut, examining the model of Greenland and drawing on semi-structured interviews with key informants (n = 45). The Greenland experience indicates that CFMs can provide access to sufficient, safe, and nutritious food on a regular basis, and can diversify locally available foods. These benefits are transferable to Nunavut, although knowledge gaps, regulatory and institutional conditions, and concerns over how CFMs might affect the cultural basis of food systems, underlies apprehension over their development in the territory. We conclude that Nunavut is not currently in the position to develop CFMs, but the role of such markets in potentially strengthening food systems should not be discounted. Future development would need to solicit community input on CFMs, resolve regulatory issues around wildlife management and harvesting, and study how future risks would affect sustainability and effectiveness. PMID- 26829008 TI - Proportionate universalism in practice? A quasi-experimental study (GoWell) of a UK neighbourhood renewal programme's impact on health inequalities. AB - Recommendations to reduce health inequalities frequently emphasise improvements to socio-environmental determinants of health. Proponents of 'proportionate universalism' argue that such improvements should be allocated proportionally to population need. We tested whether city-wide investment in urban renewal in Glasgow (UK) was allocated to 'need' and whether this reduced health inequalities. We identified a longitudinal cohort (n = 1006) through data linkage across surveys conducted in 2006 and 2011 in 14 differentially disadvantaged neighbourhoods. Each neighbourhood received renewal investment during that time, allocated on the basis of housing need. We grouped neighbourhoods into those receiving 'higher', 'medium' or 'lower' levels of investment. We compared residents' self-reported physical and mental health between these three groups over time using the SF-12 version 2 instrument. Multiple linear regression adjusted for baseline gender, age, education, household structure, housing tenure, building type, country of birth and clustering. Areas receiving higher investment tended to be most disadvantaged in terms of baseline health, income deprivation and markers of social disadvantage. After five years, mean mental health scores improved in 'higher investment' areas relative to 'lower investment' areas (b = 4.26; 95% CI = 0.29, 8.22; P = 0.036). Similarly, mean physical health scores declined less in high investment compared to low investment areas (b = 3.86; 95% CI = 1.96, 5.76; P < 0.001). Relative improvements for medium investment (compared to lower investment) areas were not statistically significant. Findings suggest that investment in housing-led renewal was allocated according to population need and this led to modest reductions in area-based inequalities in health after five years. Study limitations include a risk of selection bias. This study demonstrates how non health interventions can, and we believe should, be evaluated to better understand if and how health inequalities can be reduced through strategies of allocating investment in social determinants of health according to need. PMID- 26829006 TI - Feasibility and efficacy of early lung cancer diagnosis with chest computed tomography in HIV-infected smokers. AB - OBJECTIVE: Lung cancer screening with chest computed tomography (CT) is beneficial in smokers aged 55 to 74 years. We studied the risks, benefits and feasibility of early lung cancer diagnosis with CT in HIV-infected smokers. DESIGN AND SETTING: French, multicentre, single round chest CT study in France, realized between February 2011 and June 2012. PARTICIPANTS: Patients were HIV infected smokers at least 40 years, at least 20 pack-years, with a CD4 T lymphocyte nadir count below 350 cells/MUl. INTERVENTION: Single chest CT with a proposed standardized workup algorithm of positive images. MAIN OUTCOME MEASURE: The outcome was the number of histologically proven lung cancers diagnosed by CT with a 2-year follow-up. RESULTS: Median age of the 442 included patients was 49.8 years, 81.6% were under 55 years, 84% were men, median smoking was 30 pack years, median nadir and last CD4 cell counts were 168 and 574 cells/MUl, respectively, and 90% of patients had a plasma HIV RNA below 50 copies/ml. A positive image at baseline was reported in 94 (21%) patients, and 15 (3.4%) patients had 18 invasive procedures with no serious adverse events. Lung cancer was diagnosed in 10 patients (six at early stages), of which nine (2.0%, 95% confidence interval: 0.9-3.8) were CT detected, and eight in patients below 55 years. CONCLUSION: Early lung cancer diagnosis with CT in HIV-infected smokers was feasible, safe, and yielded a significant number of cancers. Lung cancer screening of HIV-infected smokers with an important history of immunodeficiency revealed a substantial number of cancers at younger ages than the targeted range in the general population. PMID- 26829009 TI - A duck reovirus variant with a unique deletion in the sigma C gene exhibiting high pathogenicity in Pekin ducklings. AB - A novel strain of duck reovirus (DRV) associated with a high mortality in Pekin ducklings in China, 2013, was isolated and characterized. This strain (designated as HN5d) grew well in Vero cells and produced marked cytopathic effects. HN5d contains 10 dsRNA genome segments, a typical feature of avian orthoreovirus. Following cloning, sequencing, and sequence analysis of the genome segments, a unique deletion of 18 amino acids was found in the sigma C protein of HN5d when compared with that of the recent Chinese waterfowl reoviruses (e.g., DRV 091). Phylogenetic analysis of cDNA amplicons of segments encoding for the outer capsid proteins revealed that HN5d is a novel genotype 2 waterfowl reovirus isolate. Inoculation of Pekin ducklings with HN5d resulted in splenic necrosis, a typical feature of "Duck spleen necrosis disease" (DSND) discovered in China in 2006. Unlike the typical DSND, HN5d produced severer hemorrhagic and/or necrotic lesions in livers of experimentally infected ducklings. 20-30% of death was observed during the first 7 day in the experimentally exposed birds. These findings suggest that HN5d is a novel duck reovirus isolate with severer pathogenicity in Pekin ducklings. PMID- 26829010 TI - Au Nanoparticle-Embedded Carbon Films for Electrochemical As(3+) Detection with High Sensitivity and Stability. AB - Au nanoparticle (AuNP)-embedded carbon films were formed with a one-step reproducible process by using unbalanced magnetron (UBM) cosputtering to make it possible to detect As(3+) in water. The sputtered Au components formed NPs (typically 5 nm in diameter) spontaneously in the carbon films, owing to the poor intermiscibility of Au with carbon. The surface contents of embedded AuNPs in the carbon film were widely controllable (Au = 13-21 at %) by regulating the target powers of Au and carbon individually. The obtained film had a flat surface (Ra = 0.1 nm) despite the fact the AuNPs were partially exposed at the surface. By anodic stripping voltammetry (ASV) As(3+) detection, a limit of detection of 0.55 ppb and linear dynamic range of 1-100 ppb were obtained with our electrode. These values meet the requirements imposed by international regulation. Moreover, our electrode structure realized good electrode stability for repetitive ASV measurements (relative standard deviation (RSD) = 11.7%, n = 15) because the partially embedded AuNP structures prevented the AuNPs from detaching from the surface. This result was achieved by the electrode recovery only by a potential scan from 0.1 to 1.5 V. Our electrodes can be stocked for a long time (2 years) with maintaining the electrode performance, which is very attractive for practical electrode. Selectivity test by using Tsukuba tap water added 10 ppb As(3+) and 1000 ppb Cu(2+) was successfully achieved with existence of 0.1 M EDTA (RSD = 2.6%, n = 3). The ASV results with tap water samples agreed well with those by the conventional ICPMS method. PMID- 26829011 TI - Identification of early breast cancer patient cohorts who may benefit from lapatinib therapy. AB - In resource-constrained environments many patients with human epidermal growth factor receptor 2 (HER2)+ early breast cancer are currently not offered adjuvant anti-HER2 therapy. For patients who might be able to receive the tyrosine kinase inhibitor (TKI) lapatinib (e.g. after patent expiration), it is important to identify subgroups of patients for whom anti-HER2 TKI therapy could be beneficial. To do this, we used data from 2489 patients with centrally confirmed HER2+ disease enrolled in the adjuvant Tykerb Evaluation After Chemotherapy (TEACH) trial, investigating the effect of lapatinib in patients with HER2+ early breast cancer not treated with trastuzumab. We performed subgroup analyses and number-needed-to-treat (NNT) calculations using patient and tumour associated predictors. Hormone receptor negative (HR-) patients on lapatinib had a significantly prolonged disease-free survival (DFS) compared to HR- patients on placebo (hazard ratio 0.64, P=0.003). For patients with HR- disease, starting treatment with lapatinib <=1 year from diagnosis improved DFS by 12.1% [2.1-22.1] at 2 years and 15.7% [4.1-27.2] at 5 years. Depending on lymph node status and time since diagnosis the NNT for recurrence (at 5 years) was between 5.9 (node positive patients <1 year from diagnosis) and 15.9. These numbers are in range with numbers reported for up-front adjuvant trastuzumab for HR unselected patients (e.g. 15.6 for DFS at 4 years in HERA). In a subgroup analysis of the adjuvant TEACH trial, we show that anti-HER2 monotherapy with a TKI is beneficial as adjuvant therapy in a subgroup of patients. NNT in HER2+ HR- patients are in range with those reported from up-front adjuvant trastuzumab trials. PMID- 26829012 TI - Severe neutropenia during cabazitaxel treatment is associated with survival benefit in men with metastatic castration-resistant prostate cancer (mCRPC): A post-hoc analysis of the TROPIC phase III trial. AB - BACKGROUND: Cabazitaxel significantly improves overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC) progressing during or after docetaxel, but is associated with a higher rate of grade >=3 neutropenia compared with docetaxel. We thus examined the relationship between cabazitaxel induced grade >=3 neutropenia, baseline neutrophil-lymphocyte ratio (NLR) and treatment outcomes. METHODS: Data from the experimental arm of the TROPIC phase 3 trial which randomly assigned men with mCRPC to cabazitaxel or mitoxantrone every 3 weeks, both combined with daily prednisone, were analysed. The influence on OS (primary end-point) and progression-free survival (PFS) of at least one episode of grade >=3 neutropenia during cabazitaxel therapy was investigated using Cox regression models, adjusted for pain at baseline. The relationships with prostate specific antigen (PSA) responses during cabazitaxel therapy and baseline NLR were also analysed. FINDINGS: The occurrence of grade >=3 neutropenia during cabazitaxel therapy was associated with a prolonged OS (median 16.3 versus 14.0 months, hazard ratio (HR) [95% confidence interval] = 0.65 [0.43-0.97], p = 0.035), a twice longer PFS (median 5.3 versus 2.6 months, HR = 0.56 [0.40-0.79], p = 0.001) and a higher confirmed PSA response >=50% (49.8% versus 24.4%, p = 0.005), as compared with patients who did not develop grade >=3 neutropenia. Grade >=3 neutropenia was more common in case of NLR <3 as compared with NLR >=3 at baseline (88.8% versus 75.3%, p = 0.002). Combining low NLR at baseline and grade >=3 neutropenia during therapy was associated with the longest OS (median 19.2 months) while high NLR at baseline and no grade >=3 neutropenia was associated with a poor OS (median 12.9 months, HR 0.46 [0.28-0.76], p = 0.002). In the subgroup of neutropenic patients the median OS was 19.7 months in those treated with granulocyte colony-stimulating factor (G-CSF) and 16 months on those without G-CSF support. INTERPRETATION: This post-hoc analysis of TROPIC suggests that the occurrence of grade >=3 neutropenia with cabazitaxel is associated with improved OS and PFS. Patients with a low NLR at baseline were more likely to develop grade >=3 neutropenia during cabazitaxel therapy and showed the longest OS. High NLR at baseline and no grade >=3 neutropenia during therapy was associated with poor outcomes which may suggest insufficient drug exposure or a limited impact on the tumour-associated immune response. Primary or secondary prophylactic use of G-CSF had no adverse impact for outcome. If prospectively confirmed, these results would justify maintaining the intended cabazitaxel dose of 25 mg/m(2) whenever possible. PMID- 26829014 TI - Reduced Graphene Oxide-Based Ordered Macroporous Films on a Curved Surface: General Fabrication and Application in Gas Sensors. AB - A new general method for the fabrication of a reduced graphene oxide (rGO)-based ordered monolayer macroporous film composed of a layer of closely arranged pores is introduced. Assisted by the polystyrene microsphere monolayer colloid crystal by a simple solution-heated method, pure rGO, rGO-SnO2, rGO-Fe2O3, and rGO-NiO composite monolayer ordered porous films were examplarily constructed on the curved surface of a ceramic tube widely used in gas sensors. The rGO-oxide composite porous films could exhibit much better sensing performances than those of the corresponding pure oxide films and the composite films without the ordered porous structures in detecting ethanol gas. The enhancement mechanisms induced by distinctive rGO-oxide heterojunctions and porous structures as well as the effects of the rGO content and the pore-size on the sensitivity of the composite films were systematically analyzed and discussed. This study opens up a kind of construction method for an rGO-based composite film gas sensor with uniform surface structures and high performance. PMID- 26829013 TI - Does Effectiveness of Adolescent Smoking-Cessation Intervention Endure Into Young Adulthood? 7-Year Follow-Up Results from a Group-Randomized Trial. AB - BACKGROUND: The Hutchinson Study of High School Smoking was the first randomized trial to show effectiveness of a smoking cessation intervention on 6-months prolonged smoking abstinence at one year post-intervention in a large population based sample of adolescent smokers. An important question remains: Do the positive effects from teen smoking cessation interventions seen at up to 12 months post-intervention endure into young adulthood? This study examines for the first time whether such positive early effects from teen smoking cessation intervention can endure into young adulthood in the absence of additional intervention. METHODS: High school smokers (n = 2,151) were proactively recruited into the trial from fifty randomly selected Washington State high schools randomized to the experimental (Motivational Interviewing + Cognitive Behavioral Skills Training telephone counseling intervention) or control (no intervention) condition. These smokers were followed to 7 years post high school to ascertain rates of six-year prolonged smoking abstinence in young adulthood. All statistical tests are two-sided. RESULTS: No evidence of intervention impact at seven years post high school was observed for the main endpoint of six-year prolonged abstinence, neither among all smokers (14.2% in the experimental condition vs. 13.1% in the control condition, difference = +1.1%, 95% confidence interval (CI) = -3.4 to 5.8, p = .61), nor among the subgroups of daily smokers and less-than-daily smokers, nor among other a priori subgroups. But, observed among males was some evidence of an intervention impact on two endpoints related to progress towards quitting: reduction in number of days smoked in the past month, and increase in the length of the longest quit attempt in the past year. CONCLUSIONS: There was no evidence from this trial among adolescent smokers that positive effectiveness of the proactive telephone intervention for smoking abstinence, observed previously at one year post-intervention, was sustained for the long-term into young adulthood. In light of the positive short-term effectiveness consistently observed from this and other trials for teen smokers, together with the lack of evidence from this study that such short-term impact can endure into young adulthood, sustained interventions that continue into young adulthood should be developed and tested for long-term impact. TRIAL REGISTRATION: ClinicalTrials.gov NCT00115882. PMID- 26829015 TI - Existence of Dirac cones in the Brillouin zone of diperiodic atomic crystals according to group theory. AB - We have considered non-magnetic materials with weak spin-orbit coupling, that are periodic in two non-collinear directions, and finite in the third, orthogonal direction. In some cases, the combined time-reversal and crystal symmetry of such systems, allows the existence of Dirac cones at certain points in the reciprocal space. We have investigated in a systematic way, all points of the Brillouin zone of all 80 diperiodic groups and have found sufficient conditions for the existence of s = 1/2 Dirac fermions, with symmetry-provided band touching at the vertex of the Dirac cones. Conversely, complete linear dispersion is forbidden for orbital wave functions belonging to two-dimensional (2D) irreducible representations (irreps) of little groups that do not satisfy certain group theoretical conditions given in this paper. Our results are illustrated by a tight-binding example. PMID- 26829017 TI - Two new polyhydroxylated triterpenoids from Salvia urmiensis and their cytotoxic activity. AB - Two new polyhydroxylated triterpenoids were isolated from the acetone extract of the aerial parts of Salvia urmiensis Bunge. Their structures were elucidated by 1D and 2D NMR and HR-ESI-MS analyses as olean-12-ene-1beta,3beta,11alpha,22alpha tetraol (1) and urs-12-ene-1beta,3beta,11beta,22alpha-tetraol (2). The effect of these compounds on cell viability of MCF-7 cells was investigated by the MTT assay. Compounds 1 and 2 showed weak cytotoxicity with IC50 values of 110.23 +/- 0.12 and 88.35 +/- 0.09 MUM, respectively. PMID- 26829016 TI - The Biological Effects of Bilirubin Photoisomers. AB - Although phototherapy was introduced as early as 1950's, the potential biological effects of bilirubin photoisomers (PI) generated during phototherapy remain unclear. The aim of our study was to isolate bilirubin PI in their pure forms and to assess their biological effects in vitro. The three major bilirubin PI (ZE- and EZ-bilirubin and Z-lumirubin) were prepared by photo-irradiation of unconjugated bilirubin. The individual photoproducts were chromatographically separated (TLC, HPLC), and their identities verified by mass spectrometry. The role of Z-lumirubin (the principle bilirubin PI) on the dissociation of bilirubin from albumin was tested by several methods: peroxidase, fluorescence quenching, and circular dichroism. The biological effects of major bilirubin PI (cell viability, expression of selected genes, cell cycle progression) were tested on the SH-SY5Y human neuroblastoma cell line. Lumirubin was found to have a binding site on human serum albumin, in the subdomain IB (or at a close distance to it); and thus, different from that of bilirubin. Its binding constant to albumin was much lower when compared with bilirubin, and lumirubin did not affect the level of unbound bilirubin (Bf). Compared to unconjugated bilirubin, bilirubin PI did not have any effect on either SH-SY5Y cell viability, the expression of genes involved in bilirubin metabolism or cell cycle progression, nor in modulation of the cell cycle phase. The principle bilirubin PI do not interfere with bilirubin albumin binding, and do not exert any toxic effect on human neuroblastoma cells. PMID- 26829018 TI - Invasomes of isradipine for enhanced transdermal delivery against hypertension: formulation, characterization, and in vivo pharmacodynamic study. AB - Context Isradipine is an effective calcium channel blocker used in the management of hypertension. It undergoes extensive first pass metabolism and has low oral bioavailability. Hence we attempted to develop isradipine-loaded invasomes. Objective The purpose of this work was to prepare and characterize invasomes carrier for isradipine, and to evaluate the optimized formulation obtained for pharmacodynamic study. Materials and methods Isradipine-loaded invasomes were prepared by conventional thin layer evaporation technique using Phospholipon(r) 90G, beta-citronellene (terpene) and ethanol. Prepared formulations were characterized in terms of size, size distribution, morphology, entrapment efficiency, and antihypertensive activity. Results and discussion It was observed that prepared isradipine-loaded invasomes delivers ameliorated flux, reasonable entrapment efficiency, and more effectiveness for transdermal delivery. The optimized formulation presented the particle size of 194 +/- 18 nm, entrapment efficiency (88.46%), and attained mean transdermal flux of 22.80 +/- 2.10 MUg/cm2/h through rat skin. Confocal laser scanning microscopy revealed an enhanced permeation of Rhodamine-Red-loaded isradipine invasomes to the deeper layers of the rat skin. During antihypertensive study, the treatment group showed a substantial and constant decrease in blood pressure, for up to 24 h. The isradipine invasomes formulation was found to be effective, with a 20% reduction in blood pressure by virtue of better permeation through Wistar rat skin. Conclusion It was concluded that the developed isradipine invasomes accentuate the transdermal flux and the results obtained encouraged the use of the isradipine-loaded invasomes as the formulation for the potential management of hypertension. PMID- 26829019 TI - Urinary nitrite/nitrate ratio measured by isotope-dilution LC-MS/MS as a tool to screen for urinary tract infections. AB - Urinary tract infections (UTIs) are the most common type of nosocomial infection. Traditionally, the presence of white blood cells and microorganisms in the urine provides objective evidence for UTI diagnosis. Here, we describe the use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure the nitrite and nitrate levels in urine and investigate the potential of this method for UTI diagnosis. LC-MS/MS analysis was performed in positive electrospray ionization mode. After adding (15)N-labeled internal standards and derivatizing with 2,3 diaminonaphthalene (DAN), the urinary nitrite content was directly analyzed by LC MS/MS, whereas the urinary nitrate was first reduced to nitrite before derivatization and LC-MS/MS analysis. The derivatization of nitrite and enzymatic reduction of nitrate were optimized. This method was then applied to 241 healthy subjects and 73 UTI patients. Optimization tests revealed that 1 mL of crude urine required at least 6.25 MUmol of DAN to completely derivatize nitrite and 2.5 U of nitrate reductase to completely reduce nitrate to nitrite. Urinary analysis showed that the urinary concentration of nitrite and the nitrite/nitrate ratio were higher in UTI patients than in healthy subjects. Compared with the dipstick-based urinary nitrite test and using LC-MS/MS to determine the nitrite concentration (sensitivity: 23-25%), the nitrite/nitrate ratio was significantly more sensitive (95%) and exhibited a satisfactory specificity (91%) in the screening of UTIs. Taken together, the nitrite/nitrate ratio, which reflects the reducing ability of pathogenic bacteria, could be a better method for the diagnosis of UTIs that is not subject to variations in urine specimen quality. PMID- 26829020 TI - Evaluation of Patient-Oriented, Internet-Based Information on Gender-Affirming Hormone Treatments. AB - PURPOSE: Transgender people have difficulty accessing gender-affirming hormone therapy (HT), a medically necessary treatment, in part due to a lack of provider knowledge. Patients often seek information on gender-affirming medical care using the Internet. Patients who are better informed about their own care may receive better care. This study evaluated the quantity and quality of online information about HT using several existing and novel measures. METHODS: Structured Google searches were conducted. Sites were evaluated using previously described Journal of the American Medical Association (JAMA), DISCERN, and Health On the Net (HON) criteria, for citation of the Endocrine Society Guidelines and the World Professional Association for Transgender Health (WPATH) Standards of Care (SOC), and other topic-specific measures. RESULTS: Forty sites were evaluated. The median JAMA score was 3.5/7, and the median DISCERN score was 51/80. No sites held HON certification. Citation of the Endocrine Society Guidelines and the WPATH SOC was inconsistent. Institutional sites had higher DISCERN scores compared with other sites. The presence of a bibliography was most associated with measures of quality. CONCLUSION: The quality of online information about HT is inconsistent and limited in quantity. Development of reliable online resources on HT for transgender patients is essential. Broadening awareness of key guidelines from the Endocrine Society and WPATH is essential. PMID- 26829021 TI - Impacts of visuomotor sequence learning methods on speed and accuracy: Starting over from the beginning or from the point of error. AB - The present study examined whether sequence learning led to more accurate and shorter performance time if people who are learning a sequence start over from the beginning when they make an error (i.e., practice the whole sequence) or only from the point of error (i.e., practice a part of the sequence). We used a visuomotor sequence learning paradigm with a trial-and-error procedure. In Experiment 1, we found fewer errors, and shorter performance time for those who restarted their performance from the beginning of the sequence as compared to those who restarted from the point at which an error occurred, indicating better learning of spatial and motor representations of the sequence. This might be because the learned elements were repeated when the next performance started over from the beginning. In subsequent experiments, we increased the occasions for the repetitions of learned elements by modulating the number of fresh start points in the sequence after errors. The results showed that fewer fresh start points were likely to lead to fewer errors and shorter performance time, indicating that the repetitions of learned elements enabled participants to develop stronger spatial and motor representations of the sequence. Thus, a single or two fresh start points in the sequence (i.e., starting over only from the beginning or from the beginning or midpoint of the sequence after errors) is likely to lead to more accurate and faster performance. PMID- 26829022 TI - The integration of sequential aiming movements: Switching hand and direction at the first target. AB - Movement times to a single target are typically shorter compared to when movement to a second target is required. This one target movement time advantage has been shown to emerge when participants use a single hand throughout the target sequence and when there is a switch between hands at the first target. Our goal was to investigate the lacuna in the movement integration literature surrounding the interactive effects between switching hands and changing movement direction at the first target. Participants performed rapid hand movements in five conditions; movements to a single target; two target movements with a single hand in which the second target required an extension or reversal in direction; and movements to two targets where the hands were switched at the first target and the second target required an extension or reversal in direction. The significance of including these latter two (multiple hand-multiple direction) movements meant that for the first time research could differentiate between peripheral and central processes within movement integration strategies. Reaction times were significantly shorter in the single task compared to the two target tasks. More importantly, movement times to the first target were significantly shorter in the single target task compared to all two target tasks (reflecting the so-called one target advantage), except when the second movement was a reversal movement with the same hand. These findings demonstrate for the first time the contrasting effects of movement integration at central and peripheral levels. PMID- 26829023 TI - Effects of preparation time and trial type probability on performance of anti- and pro-saccades. AB - Cognitive control optimizes responses to relevant task conditions by balancing bottom-up stimulus processing with top-down goal pursuit. It can be investigated using the ocular motor system by contrasting basic prosaccades (look toward a stimulus) with complex antisaccades (look away from a stimulus). Furthermore, the amount of time allotted between trials, the need to switch task sets, and the time allowed to prepare for an upcoming saccade all impact performance. In this study the relative probabilities of anti- and pro-saccades were manipulated across five blocks of interleaved trials, while the inter-trial interval and trial type cue duration were varied across subjects. Results indicated that inter trial interval had no significant effect on error rates or reaction times (RTs), while a shorter trial type cue led to more antisaccade errors and faster overall RTs. Responses following a shorter cue duration also showed a stronger effect of trial type probability, with more antisaccade errors in blocks with a low antisaccade probability and slower RTs for each saccade task when its trial type was unlikely. A longer cue duration yielded fewer errors and slower RTs, with a larger switch cost for errors compared to a short cue duration. Findings demonstrated that when the trial type cue duration was shorter, visual motor responsiveness was faster and subjects relied upon the implicit trial probability context to improve performance. When the cue duration was longer, increased fixation-related activity may have delayed saccade motor preparation and slowed responses, guiding subjects to respond in a controlled manner regardless of trial type probability. PMID- 26829024 TI - Content validity of workplace-based portfolios: A multi-centre study. AB - BACKGROUND: Portfolios are used as tools to coach and assess students in the workplace. This study sought to evaluate the content validity of portfolios as reflected in their capacity to adequately assess achieved competences of medical students during clerkships. METHODS: We reviewed 120 workplace portfolios at three medical universities (Belgium and the Netherlands). To validate their content, we developed a Validity Inventory for Portfolio Assessment (VIPA) based on the CanMEDS roles. Two raters evaluated each portfolio and indicated for each VIPA item whether the portfolio provided sufficient information to enable satisfactory assessment of the item. We ran a descriptive analysis on the validation data and computed Cohen's Kappa to investigate interrater agreement. RESULTS: The portfolios adequately covered the items pertaining to the communicator (90%) and professional (87%) roles. Coverage of the medical expert, collaborator, scholar and manager roles ranged between 75% and 85%. The health advocate role, covering 59%, was clearly less well represented. This role also exhibited little interrater agreement (Kappa < 0.4). CONCLUSIONS: This study lends further credence to the evidence that portfolios can indeed adequately assess the different CanMEDS roles during clerkships, the health advocate role, which was less well represented in the portfolio content, excepted. PMID- 26829025 TI - Mucosal Healing Is Associated With Improved Long-term Outcomes of Patients With Ulcerative Colitis: A Systematic Review and Meta-analysis. AB - BACKGROUND & AIMS: The paradigm for treatment for ulcerative colitis (UC) is shifting from resolving symptoms toward objective measures such as mucosal healing (MH). However, it is unclear whether MH is associated with improved long term outcomes. We performed a systematic review and meta-analysis to identify and analyze studies comparing long-term outcomes of patients with MH with those without MH. METHODS: We performed a systematic search of 3 large databases to identify prospective studies of patients with active UC that included outcomes of patients found to have MH at the first endoscopic evaluation after initiation of UC therapy (MH1) compared with those without MH1. The primary outcome was clinical remission after at least 52 weeks. Secondary outcomes included proportions of patients who were free of colectomy or corticosteroids and rate of MH after at least 52 weeks. RESULTS: We analyzed 13 studies comprising 2073 patients with active UC. Patients with MH1 had pooled odds ratio of 4.50 for achieving long-term (after at least 52 weeks) clinical remission (95% confidence interval [CI], 2.12-9.52), 4.15 for remaining free of colectomy (95% CI, 2.53 6.81), 8.40 for achieving long-term MH (95% CI, 3.13-22.53), and 9.70 for achieving long-term corticosteroid-free clinical remission (95% CI, 0.94-99.67), compared with patients without MH1. We found no difference in outcomes if patients achieved MH1 while receiving biologic versus non-biologic therapy. CONCLUSIONS: In a meta-analysis, we associated MH with long-term clinical remission, avoidance of colectomy, and corticosteroid-free clinical remission. MH is therefore appropriate goal of UC therapy. PMID- 26829026 TI - Nonselective beta-Blockers and Survival in Patients With Cirrhosis and Ascites: A Systematic Review and Meta-analysis. AB - BACKGROUND & AIMS: Nonselective beta-blockers (NSBBs), given to reduce the risk of variceal bleeding, have been associated with increased mortality in patients with cirrhosis and refractory ascites in some, but not all, studies. We performed a systematic review and meta-analysis to evaluate the effect of NSBBs on all cause mortality in patients with cirrhosis and refractory ascites. METHODS: We performed a comprehensive search of MEDLINE, Embase, Web of Science, and Scopus databases through January 2015, supplemented with a manual search. Trial-specific risk ratios (RRs) were pooled using the random-effects model. RESULTS: Our analysis included 3 randomized control trials and 8 observational studies of propranolol, carvedilol, nadolol, and metoprolol, reporting 1206 deaths among 3145 patients with ascites. The control groups received other interventions to prevent variceal bleeding. NSBB use was not associated with increased all-cause mortality in all patients with ascites (RR, 0.95; 95% confidence interval [CI], 0.67-1.35); nonrefractory ascites alone (RR, 0.96; 95% CI, 0.50-1.82), or refractory ascites alone (RR, 0.95; 95% CI, 0.57-1.61). Results were similar in randomized controlled trials and observational studies. Use of NSBBs was not associated with increased mortality at 6, 12, 18, and 24 months. Overall, the included studies had a medium to high risk of bias, except for 3 clinical trials in which the risk of biased was determined to be low. CONCLUSIONS: The use of NSBBs was not associated with a significant increase in all-cause mortality in patients with cirrhosis and ascites or refractory ascites. Certainty in the available estimates is low; a randomized trial of only patients with ascites is needed to answer this question. This meta-analysis does not support the position that NSBBs routinely be withheld from patients with ascites. PMID- 26829027 TI - Making the Cut: An Isolated Filiform Polyp. PMID- 26829028 TI - The Long Noncoding RNA SPRIGHTLY Regulates Cell Proliferation in Primary Human Melanocytes. AB - The long noncoding RNA SPRIGHTLY (formerly SPRY4-IT1), which lies within the intronic region of the SPRY4 gene, is up-regulated in human melanoma cells compared to melanocytes. SPRIGHTLY regulates a number of cancer hallmarks, including proliferation, motility, and apoptosis. To better understand its oncogenic role, SPRIGHTLY was stably transfected into human melanocytes, which resulted in increased cellular proliferation, colony formation, invasion, and development of a multinucleated dendritic-like phenotype. RNA sequencing and mass spectrometric analysis of SPRIGHTLY-expressing cells revealed changes in the expression of genes involved in cell proliferation, apoptosis, chromosome organization, regulation of DNA damage responses, and cell cycle. The proliferation marker Ki67, minichromosome maintenance genes 2-5, antiapoptotic gene X-linked inhibitor of apoptosis, and baculoviral IAP repeat-containing 7 were all up-regulated in SPRIGHTLY-expressing melanocytes, whereas the proapoptotic tumor suppressor gene DPPIV/CD26 was down-regulated, followed by an increase in extracellular signal-regulated kinase 1/2 phosphorylation, suggesting an increase in mitogen-activated protein kinase activity. Because down-regulation of DPPIV is known to be associated with malignant transformation in melanocytes, SPRIGHTLY-mediated DPPIV down-regulation may play an important role in melanoma pathobiology. Together, these findings provide important insights into how SPRIGHTLY regulates cell proliferation and anchorage-independent colony formation in primary human melanocytes. PMID- 26829029 TI - Interleukin-6 Null Mice Paradoxically Display Increased STAT3 Activity and Wound Induced Hair Neogenesis. PMID- 26829030 TI - Identification of Susceptibility Loci for Cutaneous Squamous Cell Carcinoma. AB - We report a genome-wide association study of cutaneous squamous cell carcinoma conducted among non-Hispanic white members of the Kaiser Permanente Northern California health care system. The study includes a genome-wide screen of 61,457 members (6,891 cases and 54,566 controls) genotyped on the Affymetrix Axiom European array and a replication phase involving an independent set of 6,410 additional members (810 cases and 5,600 controls). Combined analysis of screening and replication phases identified 10 loci containing single-nucleotide polymorphisms (SNPs) with P-values < 5 * 10(-8). Six loci contain genes in the pigmentation pathway; SNPs at these loci appear to modulate squamous cell carcinoma risk independently of the pigmentation phenotypes. Another locus contains HLA class II genes studied in relation to elevated squamous cell carcinoma risk following immunosuppression. SNPs at the remaining three loci include an intronic SNP in FOXP1 at locus 3p13, an intergenic SNP at 3q28 near TP63, and an intergenic SNP at 9p22 near BNC2. These findings provide insights into the genetic factors accounting for inherited squamous cell carcinoma susceptibility. PMID- 26829032 TI - Opposing Roles of JNK and p38 in Lymphangiogenesis in Melanoma. AB - In primary melanoma, the amount of vascular endothelial growth factor C (VEGF-C) expression and lymphangiogenesis predicts the probability of metastasis to sentinel nodes, but conditions boosting VEGF-C expression in melanoma are poorly characterized. By comparative mRNA expression analysis of a set of 22 human melanoma cell lines, we found a striking negative correlation between VEGF-C and microphthalmia-associated transcription factor (MITF) expression, which was confirmed by data mining in GEO databases of human melanoma Affymetrix arrays. Moreover, in human patients, high VEGF-C and low MITF levels in primary melanoma significantly correlated with the chance of metastasis. Pathway analysis disclosed the respective c-Jun N-terminal kinase and p38/mitogen-activated protein kinase activities as being responsible for the inverse regulation of VEGF C and MITF. Predominant c-Jun N-terminal kinase signaling results in a VEGF C(low)/MITF(high) phenotype; these melanoma cells are highly proliferative, show low mobility, and are poorly lymphangiogenic. Predominant p38 signaling results in a VEGF-C(high)/MITF(low) phenotype, corresponding to a slowly cycling, highly mobile, lymphangiogenic, and metastatic melanoma. In conclusion, the relative c Jun N-terminal kinase and p38 activities determine the biological behavior of melanoma. VEGF-C and MITF levels serve as surrogate markers for the respective c Jun N-terminal kinase and p38 activities and may be used to predict the risk of metastasis in primary melanoma. PMID- 26829031 TI - Immunophenotyping of Stage III Melanoma Reveals Parameters Associated with Patient Prognosis. AB - Stage III metastatic melanomas require adequate adjuvant immunotherapy to prevent relapses. Prognostic factors are awaited to optimize the clinical management of these patients. The magnitude of metastatic lymph node invasion and the BRAF(V600) activating mutation have clinical significance. Based on a comprehensive immunophenotyping of 252 parameters per patient in paired blood and metastatic lymph nodes performed in 39 metastatic melanomas, we found that blood markers were as contributive as tumor-infiltrated lymphocyte immunotypes, and parameters associated with lymphocyte exhaustion/suppression showed higher clinical significance than those related to activation or lineage. High frequencies of CD45RA(+)CD4(+) and CD3(-)CD56(-) tumor-infiltrated lymphocytes appear to be independent prognostic factors of short progression-free survival. High NKG2D expression on CD8(+)tumor-infiltrated lymphocytes, low level of regulatory T-cell tumor-infiltrated lymphocytes, and low PD-L1 expression on circulating T cells were retained in the multivariate Cox analysis model to predict prolonged overall survival. Prospective studies are needed to determine whether such immunological markers may guide adjuvant therapies in stage III metastatic melanomas. PMID- 26829033 TI - IL-6 Polymorphism and Susceptibility to Keloid Formation in a Japanese Population. PMID- 26829034 TI - Ectodysplasin A Pathway Contributes to Human and Murine Skin Repair. AB - The highly conserved ectodysplasin A (EDA)/EDA receptor signaling pathway is critical during development for the formation of skin appendages. Mutations in genes encoding components of the EDA pathway disrupt normal appendage development, leading to the human disorder hypohidrotic ectodermal dysplasia. Spontaneous mutations in the murine Eda (Tabby) phenocopy human X-linked hypohidrotic ectodermal dysplasia. Little is known about the role of EDA signaling in adult skin homeostasis or repair. Because wound healing largely mimics the morphogenic events that occur during development, we propose a role for EDA signaling in adult wound repair. Here we report a pronounced delay in healing in Tabby mice, demonstrating a functional role for EDA signaling in adult skin. Moreover, pharmacological activation of the EDA pathway in both Tabby and wild-type mice significantly accelerates healing, influencing multiple processes including re-epithelialization and granulation tissue matrix deposition. Finally, we show that the healing promoting effects of EDA receptor activation are conserved in human skin repair. Thus, targeted manipulation of the EDA/EDA receptor pathway has clear therapeutic potential for the future treatment of human pathological wound healing. PMID- 26829035 TI - Genetic Deletion of Galectin-3 Does Not Impair Full-Thickness Excisional Skin Healing. AB - Galectin-3 has been linked to the regulation of several molecular processes essential during acute cutaneous wound healing, but a comprehensive study of the role of galectin-3 has yet to be performed. With known roles in macrophage polarization, myofibroblast differentiation, re-epithelialization, and angiogenesis, we hypothesized that genetic deletion of galectin-3 would significantly impair healing of excisional skin wounds in mice. In wild-type mice, galectin-3 expression correlated temporally with the inflammatory phase of healing. Conversely, genetic deletion of galectin-3 did not alter gross wound healing kinetics even though it resulted in delayed re-epithelialization. Wound composition was not altered up to 15 days after wounding in knockout mice, and isolated dermal fibroblast function in vitro was unchanged. We further explored, spatially, the expression of galectin-3 in human chronic wound tissue in relation to the immune cell infiltrate. We show a decreased mRNA and protein abundance in the wound edge tissue, whereas markers of neutrophils, M1 and M2 macrophages are expressed abundantly. Both transforming growth factor-beta1 and tumor necrosis factor-alpha decrease galectin-3 mRNA abundance in chronic wound edge dermal fibroblasts in vitro, providing a potential mechanism for this decreased expression in chronic wounds. PMID- 26829036 TI - Age-Dependent Decrease of Mitochondrial Complex II Activity in Human Skin Fibroblasts. AB - The mitochondrial theory of aging remains one of the most widely accepted aging theories and implicates mitochondrial electron transport chain dysfunction with subsequent increasing free radical generation. Recently, complex II of the electron transport chain appears to be more important than previously thought in this process, suggested predominantly by nonhuman studies. We investigated the relationship between complex II and aging using human skin as a model tissue. The rate of complex II activity per unit of mitochondria was determined in fibroblasts and keratinocytes cultured from skin covering a wide age range. Complex II activity significantly decreased with age in fibroblasts (P = 0.015) but not in keratinocytes. This was associated with a significant decline in transcript expression (P = 0.008 and P = 0.001) and protein levels (P = 0.0006 and P = 0.005) of the succinate dehydrogenase complex subunit A and subunit B catalytic subunits of complex II, respectively. In addition, there was a significant decrease in complex II activity with age (P = 0.029) that was specific to senescent skin cells. There was no decrease in complex IV activity with increasing age, suggesting possible locality to complex II. PMID- 26829037 TI - Serum miR-16: A Potential Biomarker for Predicting Melanoma Prognosis. AB - Melanoma is among the most malignant cancers with notorious aggressiveness, and its prognosis is greatly influenced by progression status. Serum microRNAs are small noncoding RNAs with high stability and easy accessibility in human blood. Their expression profiles are frequently dysregulated in cancers; hence, levels of serum microRNAs may reflect progression status and thus predict melanoma prognosis. In a hospital based case-control study, we found a significant reduction of serum miR-16 level in melanoma patients compared with cancer-free controls (P < 0.001). In addition, serum miR-16 level markedly decreased in melanoma patients with increased tumor thickness, occurrence of ulceration, and advanced American Joint Committee on Cancer stages, and was highly correlated with tissue Ki-67 expression (r = -0.521, P < 0.0001). Kaplan-Meier analysis and Cox proportional hazards regression analysis revealed a prognostic role of serum miR-16 (hazard ratio 2.49, 95% confidence interval 1.10-5.63, P = 0.028), which independently evaluated patients' survival outcome. Finally, the suppressive role of miR-16 in melanoma growth was validated both in vitro and in vivo. In conclusion, we demonstrated that serum miR-16 is a potential biomarker for predicting melanoma prognosis. PMID- 26829038 TI - Postzygotic BRAF p.Lys601Asn Mutation in Phacomatosis Pigmentokeratotica with Woolly Hair Nevus and Focal Cortical Dysplasia. PMID- 26829040 TI - The Contribution of Diffusion Tensor Imaging to Quantitative Assessment on Multilevel Cervical Spondylotic Myelopathy. AB - BACKGROUND/AIMS: This study aimed at assessing the feasibility of diffusion tensor imaging (DTI) in multilevel cervical spondylotic myelopathy (MCSM) and quantifying the association between DTI parameters and neuronal status as a whole. METHODS: Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were obtained from 32 patients with MCSM and 21 healthy volunteers at each level. The extent of cervical cord compression was evaluated by maximum spinal cord compression (MSCC). The DTI parameters were correlated with myelopathy severity based on modified Japanese Orthopedic Association (mJOA) score in comparison with anatomic morphological and signal changes on MRI. RESULTS: There were significant differences in the DTI values between the patients and those in the control group (p < 0.001). The general mean FA values correlated with mJOA scores strongly (r = 0.507, p = 0.003), even more than MSCC (r = -0.361, p = 0.042); however, such an association was not detected between ADC values and clinical findings (p > 0.05). CONCLUSION: DTI shows a higher potential to quantitatively evaluate the whole neurological deficits of patients with MCSM. It helps us better understand the minor pathological changes within the spinal cord at an earlier stage than abnormal signal changes on MRI. PMID- 26829039 TI - Skin Microbiome Surveys Are Strongly Influenced by Experimental Design. AB - Culture-independent studies to characterize skin microbiota are increasingly common, due in part to affordable and accessible sequencing and analysis platforms. Compared to culture-based techniques, DNA sequencing of the bacterial 16S ribosomal RNA (rRNA) gene or whole metagenome shotgun (WMS) sequencing provides more precise microbial community characterizations. Most widely used protocols were developed to characterize microbiota of other habitats (i.e., gastrointestinal) and have not been systematically compared for their utility in skin microbiome surveys. Here we establish a resource for the cutaneous research community to guide experimental design in characterizing skin microbiota. We compare two widely sequenced regions of the 16S rRNA gene to WMS sequencing for recapitulating skin microbiome community composition, diversity, and genetic functional enrichment. We show that WMS sequencing most accurately recapitulates microbial communities, but sequencing of hypervariable regions 1-3 of the 16S rRNA gene provides highly similar results. Sequencing of hypervariable region 4 poorly captures skin commensal microbiota, especially Propionibacterium. WMS sequencing, which is resource and cost intensive, provides evidence of a community's functional potential; however, metagenome predictions based on 16S rRNA sequence tags closely approximate WMS genetic functional profiles. This study highlights the importance of experimental design for downstream results in skin microbiome surveys. PMID- 26829041 TI - Induction of Cell Death in Growing Human T-Cells and Cell Survival in Resting Cells in Response to the Human T-Cell Leukemia Virus Type 1 Tax. AB - Tax1 encoded by the human T-cell leukemia virus type 1 (HTLV-1) has been believed to dysregulate the expression of cellular genes involved in cell survival and mortality, leading to the development of adult T-cell leukemia (ATL). The function of Tax1 in ATL development however is still controversial, primarily because Tax1 induces cell cycle progression and apoptosis. To systemically understand cell growth phase-dependent induction of cell survival or cell death by Tax1, we established a single experimental system using an interleukin 2 (IL 2)-dependent human T-cell line Kit 225 that can be forced into resting phase by IL-2 deprivation. Introduction of Tax1 and HTLV-2 Tax (Tax2B) decreased mitochondrial activity alongside apoptosis in growing cells but not in resting cells. Cell cycle profile analysis indicated that Tax1 and Tax2B were likely to perturb the S phase in growing cells. Studies with Tax1 mutants and siRNA for NF kappaB/RelA revealed that Tax1-mediated cell growth inhibition and apoptosis in growing Kit 225 cells depend on RelA. Interestingly, inactivation of the non canonical NF-kappaB and p38 MAPK pathways relieved Tax1-mediated apoptosis, suggesting that the Tax1-NF-kappaB-p38 MAPK axis may be associated with apoptosis in growing cells. Inflammatory mediators such as CCL3 and CCL4, which are involved in oncogene-induced senescence (OIS), were induced by Tax1 and Tax2B in growing cells. In contrast, RelA silencing in resting cells reduced mitochondrial activity, indicating that NF-kappaB/RelA is also critical for Tax1-mediated cell survival. These findings suggest that Tax1-mediated cell survival and death depend on the cell growth phase. Both effects of Tax1 may be implicated in the long latency of HTLV-1 infection. PMID- 26829042 TI - Traditional Aboriginal Preparation Alters the Chemical Profile of Carica papaya Leaves and Impacts on Cytotoxicity towards Human Squamous Cell Carcinoma. AB - Carica papaya leaf decoction, an Australian Aboriginal remedy, has been used widely for its healing capabilities against cancer, with numerous anecdotal reports. In this study we investigated its in vitro cytotoxicity on human squamous cell carcinoma cells followed by metabolomic profiling of Carica papaya leaf decoction and leaf juice/brewed leaf juice to determine the effects imparted by the long heating process typical of the Aboriginal remedy preparation. MTT assay results showed that in comparison with the decoction, the leaf juice not only exhibited a stronger cytotoxic effect on SCC25 cancer cells, but also produced a significant cancer-selective effect as shown by tests on non-cancerous human keratinocyte HaCaT cells. Furthermore, evidence from testing brewed leaf juice on these two cell lines suggested that the brewing process markedly reduced the selective effect of Carica papaya leaf on SCC25 cancer cells. To tentatively identify the compounds that contribute to the distinct selective anticancer activity of leaf juice, an untargeted metabolomic approach employing Ultra High Performance Liquid Chromatography-Quadrupole Time of Flight-Mass Spectrometry followed by multivariate data analysis was applied. Some 90 and 104 peaks in positive and negative mode respectively were selected as discriminatory features from the chemical profile of leaf juice and >1500 putative compound IDs were obtained via database searching. Direct comparison of chromatographic and tandem mass spectral data to available reference compounds confirmed one feature as a match with its proposed authentic standard, namely pheophorbide A. However, despite pheophorbide A exhibiting cytotoxic activity on SCC25 cancer cells, it did not prove to be the compound contributing principally to the selective activity of leaf juice. With promising results suggesting stronger and more selective anticancer effects when compared to the Aboriginal remedy, Carica papaya leaf juice warrants further study to explore its activity on other cancer cell lines, as well as investigation to confirm the identity of compounds contributing to its selective effect, particularly those compounds altered by the long heating process applied during the traditional Aboriginal remedy preparation. PMID- 26829044 TI - Correction: Loss of Resting-State Posterior Cingulate Flexibility Is Associated with Memory Disturbance in Left Temporal Lobe Epilepsy. PMID- 26829043 TI - Arabidopsis WRKY6 Transcription Factor Acts as a Positive Regulator of Abscisic Acid Signaling during Seed Germination and Early Seedling Development. AB - The phytohormone abscisic acid (ABA) plays important roles during seed germination and early seedling development. Here, we characterized the function of the Arabidopsis WRKY6 transcription factor in ABA signaling. The transcript of WRKY6 was repressed during seed germination and early seedling development, and induced by exogenous ABA. The wrky6-1 and wrky6-2 mutants were ABA insensitive, whereas WRKY6-overexpressing lines showed ABA-hypersensitive phenotypes during seed germination and early seedling development. The expression of RAV1 was suppressed in the WRKY6-overexpressing lines and elevated in the wrky6 mutants, and the expression of ABI3, ABI4, and ABI5, which was directly down-regulated by RAV1, was enhanced in the WRKY6-overexpressing lines and repressed in the wrky6 mutants. Electrophoretic mobility shift and chromatin immunoprecipitation assays showed that WRKY6 could bind to the RAV1 promoter in vitro and in vivo. Overexpression of RAV1 in WRKY6-overexpressing lines abolished their ABA hypersensitive phenotypes, and the rav1 wrky6-2 double mutant showed an ABA hypersensitive phenotype, similar to rav1 mutant. Together, the results demonstrated that the Arabidopsis WRKY6 transcription factor played important roles in ABA signaling by directly down-regulating RAV1 expression. PMID- 26829045 TI - Cholestasis Reveals Severe Cortisol Deficiency in Neonatal Pituitary Stalk Interruption Syndrome. AB - OBJECTIVES: Cholestasis has been reported during the course of congenital hypothalamic-pituitary deficiency, but crucial information is lacking regarding both its origin and prognosis. We aimed to characterize the course of cholestasis and factors contributing to it in patients with deficiency due to pituitary stalk interruption syndrome (PSIS). METHODS: We conducted a retrospective single center, case-cohort study including 16 patients with PSIS diagnosed before one year of age. We collected clinical and biological parameters from medical records and compared the characteristics of the endocrine syndrome in PSIS patients with and without cholestasis. RESULTS: 5/16 patients had cholestasis, all with a neonatal onset and multiple hypothalamic-pituitary deficiency. Patients with cholestasis presented with lower Apgar score and higher rate of ophthalmic malformations: 3/5 vs 1/11, p = 0.03 and 5/5 vs 4/11, p = 0.02, respectively. The plasma cortisol level was strongly decreased in patients with cholestasis: 12.4 ng/mL (8-15 ng/mL) vs 79.4 ng/mL (10-210 ng/mL), p = 0.04. Cholestasis resolved within 9 months following hormone supplementation. No development of chronic liver disease was observed during a median follow-up of 9.4 years (range, 1.3 13.3 years). CONCLUSIONS: Cholestasis is a frequent symptom at presentation of PSIS during the neonatal period that may help earlier diagnosis and that indicates a profound cortisol deficiency. PMID- 26829048 TI - Hydrogen sulfide oxidation in novel Horizontal-Flow Biofilm Reactors dominated by an Acidithiobacillus and a Thiobacillus species. AB - Hydrogen Sulfide (H2S) is an odourous, highly toxic gas commonly encountered in various commercial and municipal sectors. Three novel, laboratory-scale, Horizontal-Flow Biofilm Reactors (HFBRs) were tested for the removal of H2S gas from air streams over a 178-day trial at 10 degrees C. Removal rates of up to 15.1 g [H2S] m(-3) h(-1) were achieved, demonstrating the HFBRs as a feasible technology for the treatment of H2S-contaminated airstreams at low temperatures. Bio-oxidation of H2S in the reactors led to the production of H(+) and sulfate (SO(2-)4) ions, resulting in the acidification of the liquid phase. Reduced removal efficiency was observed at loading rates of 15.1 g [H2S] m(-3) h(-1). NaHCO3 addition to the liquid nutrient feed (synthetic wastewater (SWW)) resulted in improved H2S removal. Bacterial diversity, which was investigated by sequencing and fingerprinting 16S rRNA genes, was low, likely due to the harsh conditions prevailing in the systems. The HFBRs were dominated by two species from the genus Acidithiobacillus and Thiobacillus. Nonetheless, there were significant differences in microbial community structure between distinct HFBR zones due to the influence of alkalinity, pH and SO4 concentrations. Despite the low temperature, this study indicates HFBRs have an excellent potential to biologically treat H2S-contaminated airstreams. PMID- 26829049 TI - Bromine and Iodine Contents in Raw and Cooked Shrimp and Its Parts. AB - The concentration of bromine and iodine was determined in shrimp and its parts (tissue and shells), and changes in the analyte concentration were evaluated after the cooking procedure. Bromine and iodine concentrations were determined by a method recently developed by our research group based on microwave-induced combustion for sample preparation and inductively coupled plasma mass spectrometry for analyte determination. The accuracy was evaluated using a reference material (NIST 8414) that was digested using the proposed method. No statistical difference was observed between certified and determined values (Student's t test, 95% confidence level). Suitable limits of detection (Br, 0.02 MUg g(-1) and I, 0.01 MUg g(-1)) were obtained for both analytes. Higher concentrations of both analytes were observed in shrimp shells in comparison to shrimp tissue for raw and cooked samples. Moreover, losses of Br and I (between 24 and 43%) were observed after cooking. PMID- 26829050 TI - Concepts in cardio-oncology: definitions, mechanisms, diagnosis and treatment strategies of cancer therapy-induced cardiotoxicity. AB - There has been considerable improvement in cancer survival rates, primarily through improved preventive strategies and novel anticancer drugs. Cancer is now becoming a chronic illness and as such both short and long-term cardiotoxic effects of cancer therapy are becoming more apparent. This has led to the emergence of a new multidisciplinary specialty known as cardio-oncology, with the purpose of identifying patients who are at a higher risk for developing cardiotoxicity so that appropriate surveillance, treatment and follow-up strategies may be instituted early. The mechanisms of cardiotoxicity caused by commonly used anticancer agents are reviewed, along with the latest advances in diagnostic and preventative strategies, with the overall objective of allowing cancer patients to continue both lifesaving and palliative treatments for their malignancy. PMID- 26829051 TI - Caspases uncouple p27(Kip1) from cell cycle regulated degradation and abolish its ability to stimulate cell migration and invasion. AB - In addition to their role in programmed cell death, caspases exert non-lethal functions in diverse developmental processes including cell differentiation or tissue remodeling. Terminal cell cycle exit and differentiation can be promoted by increased level of the CDK inhibitor p27(Kip1). Activated caspases cause proteolytic processing of p27, and we identified a novel caspase cleavage site in human p27 that removes a C-terminal fragment of 22 amino acids from the CDK inhibitor, including a phosphodegron. Thereby, caspases protect the inhibitor from SCF-Skp2-mediated degradation in S, G2 and M phases of the cell cycle. As a consequence, p27 becomes stabilized and remains an efficient nuclear inhibitor of cell cycle progression. Besides controlling cyclin/CDK kinase activity, p27 also regulates cytoskeletal dynamics, cell motility and cell invasion. Following processing by caspases, p27 fails to bind to RhoA and to inhibit its activation, and thereby abolishes the ability of p27 to stimulate cell migration and invasion. We propose that the stabilization of the CDK inhibitor and elimination of RhoA-induced cytoskeletal remodeling upon caspase processing could contribute to cell cycle exit and cytoskeletal remodeling during non-lethal caspase controlled differentiation processes. PMID- 26829053 TI - ALK(R1275Q) perturbs extracellular matrix, enhances cell invasion and leads to the development of neuroblastoma in cooperation with MYCN. AB - Overexpression of MYCN is a hallmark of neuroblastoma (NB). ALK(R1275Q), an activating mutation of ALK (anaplastic lymphoma kinase), has been found in sporadic and familial NB patients. In this report, we demonstrated that ALK(R1275Q) knock-in, MYCN transgenic compound mice developed NB with complete penetrance. Transcriptome analysis revealed that ALK(R1275Q) globally downregulated the expression of extracellular matrix (ECM)- and basement membrane (BM)-associated genes in both primary neuronal cells and NB tumors. Accordingly, ALK(R1275Q)/MYCN tumors exhibited reduced expression of ECM/BM-related proteins as compared with MYCN tumors. In addition, on MYCN transduction, ALK(R1275Q) expressing neuronal cells exhibited increased migratory and invasive activities. Consistently, enhanced invasion and metastasis were demonstrated in ALK(R1275Q)/MYCN mice. These results collectively indicate that ALK(R1275Q) confers a malignant potential on neuronal cells that overexpress MYCN by impairing normal ECM/BM integrity and enhancing tumor growth and dissemination. Moreover, we found that crizotinib, an ALK inhibitor, almost completely inhibited the growth of ALK(R1275Q)/MYCN tumors in an allograft model. Our findings provided insights into the cooperative mechanism of the mutated ALK and overexpressed MYCN in the pathogenesis of NB and demonstrated the effectiveness of crizotinib on ALK(R1275Q)-positive tumors. PMID- 26829054 TI - Induction Therapy for Lung Transplantation in COPD: Analysis of the UNOS Registry. AB - Although studies demonstrate that induction therapy improves outcomes after lung transplantation, its influence on survival in patients with chronic obstructive pulmonary disease (COPD) is not clear. The United Network for Organ Sharing database was queried to obtain data regarding adult patients with COPD receiving lung transplant between May 2005 and June 2014. Therapies evaluated include anti thymocyte globulin, anti-lymphocyte globulin, thymoglobulin, basiliximab, and alemtuzumab. Data were categorized based on receiving induction (INDUCED) and no induction (NONE). Kaplan-Meier plots, Cox proportional hazards models of patient survival, and competing-risks regression models for secondary endpoints were utilized. A total of 3,405 patients who underwent lung transplantation for COPD were enrolled with 1,761 (52%) receiving induction therapy. Of INDUCED, 1,146 (65%) received basiliximab, 380 (22%) received alemtuzumab, and 235 (13%) received a polyclonal preparation. The hazard ratio for INDUCED vs. NONE was 0.793 (95% CI = 0.693, 0.909; p = 0.001) in the fully adjusted Cox model. A multivariable competing-risks model also found a protective influence of induction therapy with respect to delayed onset of bronchiolitis obliterans syndrome after transplantation (SHR = 0.801; 95% CI = 0.694, 0.925; p = 0.003). In a cohort of recently transplanted patients with COPD, there appears to be a benefit from contemporary induction agents with no concurrent increase in the risk of death due to infection. PMID- 26829055 TI - van der Waals Solids from Self-Assembled Nanoscale Building Blocks. AB - Traditional atomic van der Waals materials such as graphene, hexagonal boron nitride, and transition metal dichalcogenides have received widespread attention due to the wealth of unusual physical and chemical behaviors that arise when charges, spins, and vibrations are confined to a plane. Though not as widespread as their atomic counterparts, molecule-based two-dimensional (2D) layered solids offer significant benefits; their structural flexibility will enable the development of materials with tunable properties. Here we describe a layered van der Waals solid self-assembled from a structure-directing building block and C60 fullerene. The resulting crystalline solid contains a corrugated monolayer of neutral fullerenes and can be mechanically exfoliated. The absorption spectrum of the bulk solid shows an optical gap of 390 +/- 40 meV that is consistent with thermal activation energy obtained from electrical transport measurement. We find that the dimensional confinement of fullerenes significantly modulates the optical and electronic properties compared to the bulk solid. PMID- 26829052 TI - Eukaryotic initiation factor 4E-binding protein 1 (4E-BP1): a master regulator of mRNA translation involved in tumorigenesis. AB - Protein synthesis activity is abnormally enhanced in cancer cells to support their uncontrolled growth. However, this process needs to be tightly restricted under metabolic stress-a condition often found within the tumor microenvironment to preserve cell viability. mTORC1 is critical to link protein synthesis activity to nutrient and oxygen levels, in part by controlling the 4E-BP1-eIF4E axis. Whereas mTORC1 and eIF4E are known pro-tumorigenic factors, whose expression or activity is increased in numerous cancers, the role of 4E-BP1 in cancer is not yet definitive. On the one hand, 4E-BP1 has tumor suppressor activity by inhibiting eIF4E and, thus, blocking mRNA translation and proliferation. This is corroborated by elevated levels of phosphorylated and hence inactive 4E-BP1, which are detected in various cancers. On the other hand, 4E-BP1 has pro tumorigenic functions as it promotes tumor adaptation to metabolic and genotoxic stress by selectively enhancing or preventing the translation of specific transcripts. Here we describe the molecular and cellular functions of 4E-BP1 and highlight the distinct roles of 4E-BP1 in cancer depending on the microenvironmental context of the tumor. PMID- 26829058 TI - Het brein van farao tot fMRI. Een fenomenale ontdekkingsreis [The Brain, From Pharaoh to fMRI. An Extraordinary Journey Through the History of Brain Science], by Kees Brunia. PMID- 26829060 TI - Kurtosis imaging reveals microstructural changes of late-stage alpha-synuclein accumulation in a mouse model of Parkinson's disease. AB - This article is a critique of the paper by Khairnar et al. in the current issue of the Journal of Neurochemistry which describes the use of a sophisticated magnetic resonance imaging technique, diffusion kurtosis imaging, to investigate microstructural changes in the brain of TNWT-61 mice that are over-expressing alpha-synuclein. The importance of alpha-synuclein to Parkinson's disease pathology is considered and the article critically assessed. The steps needed to establish this method as a biomarker in human disease is discussed. Read the highlighted article 'Late-stage alpha-synuclein accumulation in TNWT-61 mouse model of Parkinson's disease detected by diffusion kurtosis imaging' on page 1259. PMID- 26829056 TI - Combination chemoprevention with grape antioxidants. AB - Antioxidant ingredients present in grape have been extensively investigated for their cancer chemopreventive effects. However, much of the work has been done on individual ingredients, especially focusing on resveratrol and quercetin. Phytochemically, whole grape represents a combination of numerous phytonutrients. Limited research has been done on the possible synergistic/additive/antagonistic interactions among the grape constituents. Among these phytochemical constituents of grapes, resveratrol, quercetin, kaempferol, catechin, epicatechin, and anthocyanins (cyanidin and malvidin) constitute more than 70% of the grape polyphenols. Therefore, these have been relatively well studied for their chemopreventive effects against a variety of cancers. While a wealth of information is available individually on cancer chemopreventive/anti proliferative effects of resveratrol and quercetin, limited information is available regarding the other major constituents of grape. Studies have also suggested that multiple grape antioxidants, when used in combination, alone or with other agents/drugs show synergistic or additive anti-proliferative response. Based on strong rationale emanating from published studies, it seems probable that a combination of multiple grape ingredients alone or together with other agents could impart 'additive synergism' against cancer. PMID- 26829059 TI - Identification of a new locus and validation of previously reported loci showing differential methylation associated with smoking. The REGICOR study. AB - Smoking increases the risk of many diseases and could act through changes in DNA methylation patterns. The aims of this study were to determine the association between smoking and DNA methylation throughout the genome at cytosine-phosphate guanine (CpG) site level and genomic regions. A discovery cross-sectional epigenome-wide association study nested in the follow-up of the REGICOR cohort was designed and included 645 individuals. Blood DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip. Smoking status was self-reported using a standardized questionnaire. We identified 66 differentially methylated CpG sites associated with smoking, located in 38 genes. In most of these CpG sites, we observed a trend among those quitting smoking to recover methylation levels typical of never smokers. A CpG site located in a novel smoking-associated gene (cg06394460 in LNX2) was hypomethylated in current smokers. Moreover, we validated two previously reported CpG sites (cg05886626 in THBS1, and cg24838345 in MTSS1) for their potential relation to atherosclerosis and cancer diseases, using several different approaches: CpG site methylation, gene expression, and plasma protein level determinations. Smoking was also associated with higher THBS1 gene expression but with lower levels of thrombospondin-1 in plasma. Finally, we identified differential methylation regions in 13 genes and in four non-coding RNAs. In summary, this study replicated previous findings and identified and validated a new CpG site located in LNX2 associated with smoking. PMID- 26829061 TI - Age-associated deterioration in follicular fluid induces a decline in bovine oocyte quality. AB - Maternal age affects the quality of oocytes. The present study examined whether follicular fluid (FF) is a casual factor for age-associated decline in oocyte quality. First, we measured the concentration of advanced glycation end-products (AGE) in FF derived from young (21-45 months; Young-FF) and aged (>=120 months; Aged-FF) cows and found significantly higher concentrations of AGE in Aged-FF than Young-FF. Second, oocytes were collected from ovaries of young or aged cows and cultured in maturation medium containing 10% FF derived from young or aged cows. Regardless of oocyte origin, Aged-FF accelerated nuclear maturation progression and gap junction closure between oocytes and cumulus cells, increased reactive oxygen species (ROS) content and the rate of abnormal fertilisation of oocytes and decreased blastulation rate compared with Young-FF. Furthermore, supplementation of maturation medium with AGE induced similar age-associated events in oocytes derived from young cows, in that AGE accelerated the progression of nuclear maturation, increased ROS content in oocytes, increased the rate of abnormal fertilisation and decreased blastulation rate. In conclusion, maternal aging increased the concentration of AGE in FF, and both AGE and Aged-FF accelerated nuclear maturation and reduced the developmental competence of oocytes. PMID- 26829062 TI - Ru(bpy)3(2+)/nanoporous silver-based electrochemiluminescence immunosensor for alpha fetoprotein enhanced by gold nanoparticles decorated black carbon intercalated reduced graphene oxide. AB - A highly sensitive sandwich-type electrochemiluminescence (ECL) immunosensor was proposed for the quantitative determination of alpha fetoprotein (AFP) using gold nanoparticles decorated black carbon intercalated reduced graphene oxide (Au rGO@CB) as sensing platform and nanoporous silver (NPS) loaded Ru(bpy)3(2+) as labels. In this work, intercalation of CB inhibited the accumulation of rGO and Au-rGO@CB was firstly used to immobilize primary antibody (Ab1) in ECL system. NPS prepared by the dealloying of binary alloy has high pore volume and surface areas, which was used to load amount of secondary antibodies (Ab2) and Ru(bpy)3(2+), which could greatly enhance the ECL intensity. Under optimal conditions, the designed immunosensor exhibited wider linear range from 0.0001 to 30 ng/mL with a relative lower detection limit of 33 fg/mL for AFP detection. Overall, the designed immunosensor exhibited high sensitivity and selectivity, good repeatability and stability. This proposed method provided a potential application for clinical monitoring of AFP. PMID- 26829064 TI - Alcohol Expectancies, Posttraumatic Stress Disorder, and Alcohol Use in College Students With a History of Childhood Trauma. AB - OBJECTIVE: Prior research has emphasized that the key mediator in the posttraumatic stress disorder (PTSD) symptom-alcohol use relationship is the expectancy of alcohol's tension-reducing properties. This study extends the literature by examining various alcohol outcome expectancies. METHODS: Cross sectional data were obtained from 198 college students who reported experiencing at least one traumatic event in childhood. Participants answered surveys measuring PTSD symptoms, alcohol outcome expectancies, and three measures of alcohol consumption and related problems. RESULTS: Participants included 131 males (mean age = 19.65 years, SD = 1.06, range = 18 to 24) and 67 females (mean age = 19.43 years, SD = 0.82, range = 18 to 23), who were predominantly European American (82%). For males and females, results of the multivariate analyses suggested that self-perception expectancies mediated the effects of PTSD symptoms on alcohol use severity, whereas sociability expectancies mediated the effects of PTSD symptoms on monthly alcohol use. For women, risk and aggression and sexuality expectancies mediated the relationship between PTSD symptoms and alcohol use severity, while risk and aggression expectancies mediated the relationship between PTSD symptoms and alcohol use consequences. For men, sociability expectancies mediated the effects of PTSD symptoms on alcohol use severity. Across genders, tension-reduction expectancies did not mediate the relationship between PTSD symptom and the three alcohol measures. CONCLUSIONS: This study was unable to find support for the self-medication hypothesis via the tension-reduction outcome expectancy pathway. However, other significant findings can be interpreted in light of the self-medication hypothesis. For example, alcohol may aid in coping with social impairments related to PTSD symptoms, particularly in a college sample. This study also highlighted gender differences in the association between PTSD symptoms and alcohol consumption and related problems. PMID- 26829063 TI - Value of serial preablative thyroglobulin measurements: can we address the impact of thyroid remnants? AB - OBJECTIVE: Preablative stimulated thyroglobulin (ps-Tg) is somewhat nonspecific when used as a predictive marker for distant metastases (DM) from differentiated thyroid carcinoma because of the impact of residual tissue postsurgery. The aim of this study was to explore the potential value of serial ps-Tg measurements and assess the clinical value of these measurements in the context of thyroid remnants. MATERIALS AND METHODS: A total of 370 consecutive differentiated thyroid carcinoma patients with serial measurements of ps-Tg, thyrotropin (TSH), and anti-Tg antibody before radioactive iodine ablation were included in the study. Patients were divided into those with DM (n=76) and non-DM with no remnant thyroid (NRT, n=53), moderate remnant thyroid (MRT, n=206), and overt remnant thyroid (ORT, n=35) on the basis of uptake in the thyroid bed on the whole-body I scan. The initial ps-Tg and the last one collected immediately before radioactive iodine ablation were marked as Tg1 and Tg2, respectively, with a median interval of 8 days. The change was marked as DeltaTg. The same was applied for serum TSH values. Both single parameters (Tg1, Tg2) and DeltaTg were compared among different groups. The velocity of ps-Tg change as well as DeltaTg/DeltaTSH was also used to alleviate the impact of time and TSH levels on ps-Tg. RESULTS: Patients with ORT presented with significantly higher single ps-Tg values than those with MRT and NRT (both P<0.01), with the highest initial Tg value of 194.4 ng/ml, which was higher than most patients with DM (median: 104.3 ng/ml). However, no differences were observed among ORT, MRT, and NRT when DeltaTg, velocity of ps-Tg change, or DeltaTg/DeltaTSH was used as an index (both P>0.05), which implies that the change parameters can be used as predictors of DM involvement even in the context of significant residual thyroid tissue. CONCLUSION: In comparison with a single ps-Tg measurement, changes in ps-Tg values even over as short an interval as 8 days can provide clinical guidance for possible metastatic involvement even in the context of significant thyroid remnant tissue. PMID- 26829065 TI - Two-Year Therapeutic Effectiveness of Varenicline for Smoking Cessation in a Real World Setting. AB - BACKGROUND: Varenicline is an effective smoking cessation therapy in clinical trials. However, its effectiveness might vary in a real world setting and its long term effectiveness (2-year) has not been reported yet. OBJECTIVE: The objective was ascertaining the effectiveness of varenicline in the treatment of tobacco consumption in Primary Care settings. METHODS: Observational, multicenter, retrospective study using medical records of smokers followed for 24 months. Sociodemographic characteristics, comorbidity, type of treatment (varenicline with or without group therapy), and smoking characteristics (Fagestrom and Richmond tests, starting age, number of cigarettes, cessation attempts, and initial CO-oximeter measurements) were evaluated. RESULTS: 773 smokers treated with varenicline (72.4%) or varenicline combined with group therapy (27.6%) were included. Mean age was 43.6 years [51.7% male (n = 400)]. Continuous abstinence rate at 24 months was 44.4%, with no significant gender or age differences. Median cessation time was 398 days (95%CI: 376-421). A clear association was detected between the probability of remaining abstinent at 24 months and participation in group therapy (OR: 1.877, 95%CI: 1.362-2.589), as well as treatment adherence (compliance >80%) (OR: 6.556, 95%CI: 5.870-7.242), but not with co-financing of treatment (observed in 77% of patients). For every day that varenicline was taken, abstinence increased by an average of 6.6 days. CONCLUSIONS: This retrospective cohort study suggests that 2-year effectiveness of varenicline might be substantial in a real world setting. The abstinence rate was higher for those who also receive group therapy. PMID- 26829066 TI - Positive effects of egg-derived phospholipids in patients with metabolic syndrome. AB - PURPOSE: Patients with metabolic syndrome (MBS) have an increased risk of all cause mortality, especially from cardiovascular disease. Egg phospholipids (PL) have been shown to exert a positive impact on cholesterol metabolism and inflammation; eggs are an important source of PL. Our study examined potential effects of egg-yolk-derived PL in non-diabetic patients with MBS. METHODS: The study group consisted of 40 patients with MBS diagnosed according to IDF criteria and divided into an experimental group receiving the PL preparation (n-6: n-3 fatty acids ratio: 1.79) and the comparison group receiving an olive oil preparation, for one month (2012/2013year). The studied dosage was 45ml (15ml 3 times per day). It was a randomized, double blinded study. RESULTS: The waist to hip ratio, GGTP levels, plasma platelet concentrations and flow mediated vasodilation of brachial artery (FMD) significantly improved in the experimental group. A significant decrease in daytime ABPM blood pressure was noticed in both groups. CONCLUSIONS: A phospholipid-enriched diet caused a significant improvement of endothelial vasodilatory function and a significant decrease in waist to hip ratio. A significant decrease in daytime systolic blood pressure were observed in both the phospholipid-enriched and oil-olive group. PMID- 26829067 TI - Adipose tissue infiltration in normal-weight subjects and its impact on metabolic function. AB - Discordant phenotypes, metabolically healthy obese and unhealthy normal-weight individuals, are always interesting to provide important insights into the mechanistic link between adipose tissue dysfunction and associated metabolic alterations. Macrophages can release factors that impair the proper activity of the adipose tissue. Thus, studying subcutaneous and visceral adipose tissues, we investigated for the first time the differences in monocyte/macrophage infiltration, inflammation, and adipogenesis of normal-weight subjects who differed in their degree of metabolic syndrome. The study included 92 normal weight subjects who differed in their degree of metabolic syndrome. Their anthropometric and biochemical parameters were measured. RNA from subcutaneous and visceral adipose tissues was isolated, and mRNA expression of monocyte/macrophage infiltration (CD68, CD33, ITGAM, CD163, EMR-1, CD206, MerTK, CD64, ITGAX), inflammation (IL-6, tumor necrosis factor alpha [TNFalpha], IL-10, IL-1b, CCL2, CCL3), and adipogenic and lipogenic capacity markers (PPARgamma, FABP4) were measured. Taken together, our data provide evidence of a different degree of macrophage infiltration between the adipose tissues, with a higher monocyte/macrophage infiltration in subcutaneous adipose tissue in metabolically unhealthy normal-weight subjects, whereas visceral adipose tissue remained almost unaffected. An increased macrophage infiltration of adipose tissue and its consequences, such as a decrease in adipogenesis function, may explain why both the obese and normal-weight subjects can develop metabolic diseases or remain healthy. PMID- 26829068 TI - Influence of pH and media composition on suspension stability of silver, zinc oxide, and titanium dioxide nanoparticles and immobilization of Daphnia magna under guideline testing conditions. AB - In aquatic toxicity testing of engineered nanoparticles (ENPs) the process of agglomeration is very important as it may alter bioavailability and toxicity. In the present study, we aimed to identify test conditions that are favorable for maintaining stable ENP suspensions. We evaluated the influence of key environmental parameters: pH (2-12) and ionic strength using M7, Soft EPA (S EPA) medium, and Very Soft EPA (VS EPA) medium; and observed the influence of these parameters on zeta potential, zeta average, and acute immobilization of Daphnia magna for three different ENPs. Despite being sterically stabilized, test suspensions of silver (Ag) ENPs formed large agglomerates in both VS EPA and M7 media; and toxicity was found to be higher in VS EPA medium due to increased dissolution. Low-agglomerate suspensions for zinc oxide (ZnO) could be obtained at pH 7 in VS EPA medium, but the increase in dissolution caused higher toxicity than in M7 medium. Titanium dioxide (TiO2) ENPs had a point of zero charge in the range of pH 7-8. At pH 7 in VS EPA, agglomerates with smaller hydrodynamic diameters (~200nm) were present compared to the high ionic strength M7 medium where hydrodynamic diameters reached micrometer range. The stable suspensions of TiO2 ENPs caused immobilization of D. magna, 48-h EC50 value of 13.7mgL(-1) (95% CI, 2.4mg-79.1mgL(-1)); whereas no toxicity was seen in the unstable, highly agglomerated M7 medium suspensions, 48-h EC50 >100mgL(-1). The current study provides a preliminary approach for methodology in testing and assessing stability and toxicity of ENPs in aquatic toxicity tests of regulatory relevance. PMID- 26829069 TI - Toxicological and chemical investigation of untreated municipal wastewater: Fraction- and species-specific toxicity. AB - Absence of a municipal wastewater (WW) treatment plant results in the untreated WW discharge into the recipient. The present study investigated toxic effects and chemical composition of water extracts and fractions from untreated WW and recipient Danube River (DR). Samples were prepared by solid-phase extraction and silica gel fractionation and screened for EROD activity and cytotoxicity using aquatic models, comprising of fish liver cells (PLHC-1) and a model of the early development of zebrafish embryos, while rat (H4IIE) and human (HepG2) hepatoma cells served as mammalian models. Polar fraction caused cytotoxicity and increased the EROD activity in PLHC-1 cells, and increased mortality and developmental abnormalities in developing zebrafish embryos. In H4IIE, polar fraction induced inhibition of cell growth and increased EROD activity, whereas HepG2 exerted low or no response to the exposure. Non-polar and medium-polar fractions were ineffective. Tentative identification by GC/MS showed that WW is characterized by the hydrocarbons, alkylphenols, plasticizers, and a certain number of benzene derivatives and organic acids. In DR, smaller number of organic compounds was identified and toxicity was less pronounced than in WW treatments. The present study revealed the potent toxic effect of polar fraction of untreated WW, with biological responses varying in sensitivity across organisms. Obtained results confirmed that fraction- and species-specific toxicity should be considered when assessing health risk of environmental pollution. PMID- 26829071 TI - Puckering Energetics and Optical Activities of [7]Circulene Conformers. AB - The structural preference of [7]circulene is analyzed by taking into account vibronic interactions. DFT calculations reveal that pseudo-Jahn-Teller effects cause the D7h-symmetry structure to relax to C2- and Cs-symmetry structures, which are both ca. 9 kcal/mol lower in energy than the D7h structure. In energy terms, the C2-symmetry structure is 0.05 kcal/mol lower than that of the Cs symmetry. The active vibrations are attributed to low-frequency puckering modes that are coupled with pi-sigma excitation states. The optical activities of the C2-symmetry structure were simulated by configuration interaction calculations, and the simulated CD/ORD spectra were reasonable and consistent with the experimental data. The optical rotatory strengths obeyed the helix rule; that is, the left-handed helix shows negative Cotton effects through the antisymmetric excited states. The calculated spectra will serve as a foundation for further investigation of optical activities of negatively curved structures. PMID- 26829072 TI - Second-Order Peer Reviews of Clinically Relevant Articles for the Physiatrist: What Works for Chronic Whiplash-Associated Disorders: Neck-Specific Exercises With or Without Behavioral Modification? PMID- 26829070 TI - Bioaccumulation, oxidative stress and genotoxicity in fish (Channa punctatus) exposed to a thermal power plant effluent. AB - Metal bioaccumulation and induction of biomarkers such as lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione S transferase (GST), reduced glutathione (GSH) and DNA damage are potential indicators of stress in Channa punctatus exposed to effluents. In canal water, receiving thermal power plant discharges, Fe and Ni concentrations exceeded the recommended guidelines set by the United Nations Environment Programme Global Environment Monitoring System (UNEPGEMS). Fe was highly bioavailable and accumulated in all organs (liver, kidney, muscle and integument). The highest metal pollution index (MPI) value of 41.2 was observed in kidney and the lowest 13.5 in muscle tissue. LPO, SOD, CAT and GST levels were significantly higher in liver and kidney, whereas GSH levels declined significantly compared to fish from the reference site. Concomitant damage to DNA was observed with significantly higher mean tail length in the exposed fish gill cells (26.5um) and in liver (20.8um) compared to reference fish. Therefore, it can be concluded that the thermal power plant effluent had the potential to cause oxidative stress and DNA damage in C. punctatus. PMID- 26829073 TI - Investigation of the Comparative Effects of Red and Infrared Laser Therapy on Skeletal Muscle Repair in Diabetic Rats. AB - OBJECTIVE: The aim of this study was to evaluate the in vivo response of 2 different laser wavelengths (red and infrared) on skeletal muscle repair process in diabetic rats. DESIGN: Forty Wistar rats were randomly divided into 4 experimental groups: basal control-nondiabetic and muscle-injured animals without treatment (BC); diabetic muscle-injured without treatment (DC); diabetic muscle injured, treated with red laser (DCR) and infrared laser (DCIR). The injured region was irradiated daily for 7 consecutive days, starting immediately after the injury using a red (660 nm) and an infrared (808 nm) laser. RESULTS: The histological results demonstrated in both treated groups (red and infrared wavelengths) a modulation of the inflammatory process and a better tissue organization located in the site of the injury. However, only infrared light significantly reduced the injured area and increased MyoD and myogenin protein expression. Moreover, both red and infrared light increased the expression of the proangiogenic vascular endothelial growth factor and reduced the cyclooxygenase 2 protein expression. CONCLUSION: These results suggest that low-level laser therapy was efficient in promoting skeletal muscle repair in diabetic rats. However, the effect of infrared wavelength was more pronounced by reducing the area of the injury and modulating the expression proteins related to the repair. PMID- 26829075 TI - Can Quantification of Biceps Peritendinous Effusion Predict Rotator Cuff Pathologies?: A Retrospective Analysis of 1352 Shoulder Ultrasound. AB - OBJECTIVE: The purposes of this study were to determine the best cutoff value for bicipital peritendinous effusion (BPE) and to test its diagnostic performance as regards shoulders with and without rotator cuff pathology. DESIGN: We reviewed the sonographic reports of 1352 patients with suspected shoulder disorders between January 2011 and June 2012. The associations between BPE and rotator cuff abnormalities were explored by logistic regression and adjusted for age, sex, affected side, and clinical diagnosis of frozen shoulder. The receiver operating characteristic curves were constructed to assess the ability of BPE to discriminate certain rotator cuff pathologies. Maximal Youden indexes were used to define the best cutoff points, which were later applied on the validation data set for its discriminative ability. RESULTS: Sonographic findings of subscapularis tendinopathy, subdeltoid bursitis, supraspinatus full-thickness tear, and supraspinatus articular-sided partial-thickness tear were found to be associated with BPE. The cutoff values of BPE to differentiate those lesions were 1.0, 0.9, 1.5, and 1.5 mm, respectively. Validation of the diagnostic performance of BPE at defined thicknesses yielded good negative predictive values for the aforementioned rotator cuff abnormalities. CONCLUSIONS: Sonographically detected BPE seems to be in association with certain rotator cuff pathologies, and it can be utilized as an adjuvant finding to rule out such rotator cuff abnormalities. PMID- 26829076 TI - Re: Quadriceps Fat Pad Impingement and Synovial Hypertrophy with Mild to Moderate Lipoma Arborescens. PMID- 26829074 TI - Combining Dopaminergic Facilitation with Robot-Assisted Upper Limb Therapy in Stroke Survivors: A Focused Review. AB - Despite aggressive conventional therapy, lasting hemiplegia persists in a large percentage of stroke survivors. The aim of this article is to critically review the rationale behind targeting multiple sites along the motor learning network by combining robotic therapy with pharmacotherapy and virtual reality-based reward learning to alleviate upper extremity impairment in stroke survivors. Methods for personalizing pharmacologic facilitation to each individual's unique biology are also reviewed. At the molecular level, treatment with levodopa was shown to induce long-term potentiation-like and practice-dependent plasticity. Clinically, trials combining conventional therapy with levodopa in stroke survivors yielded statistically significant but clinically unconvincing outcomes because of limited personalization, standardization, and reproducibility. Robotic therapy can induce neuroplasticity by delivering intensive, reproducible, and functionally meaningful interventions that are objective enough for the rigors of research. Robotic therapy also provides an apt platform for virtual reality, which boosts learning by engaging reward circuits. The future of stroke rehabilitation should target distinct molecular, synaptic, and cortical sites through personalized multimodal treatments to maximize motor recovery. PMID- 26829077 TI - Transcutaneous Electrical Nerve Stimulation for Management of Limb Spasticity: A Systematic Review. AB - The purpose of this systematic review was to summarize the effect of transcutaneous electrical nerve stimulation (TENS) for management of limb spasticity. Randomized controlled trials were searched using electronic databases through July 2015. Fourteen randomized controlled trials were included, involving 544 participants. Intervention protocols fit within three categories: 1) TENS vs. no TENS or placebo TENS (n = 7), 2) TENS vs. another TENS protocol or another intervention for spasticity management (n = 7), and 3) TENS as an adjunct to another intervention for spasticity management (n = 4). There was level 1 and 2 evidence for TENS improving spasticity-related outcome measures within the International Classification of Functioning, Disability, and Health domains of body structure and function (e.g., Modified Ashworth Scale) as well as activity (e.g., gait). Better responses in outcome measures in the International Classification of Functioning, Disability, and Health activity domain were seen when TENS was used in combination with active therapy (e.g., exercise and task related training) vs. as a single therapeutic modality. PMID- 26829078 TI - Rehabilitation of Susac Syndrome: A Case Report. AB - A 43-yr-old man presented with headaches, forgetfulness, and personality changes. Based on imaging, there was concern for acute disseminated encephalomyelitis. He improved with steroids and immunoglobulin. When symptoms recurred, magnetic resonance imaging showed new scattered gray and white matter lesions, many within the corpus callosum. Angiogram showed multiple branch retinal artery occlusions, pathognomonic for Susac syndrome. He was treated with steroids, intravenous immunoglobulin, and cytoxan and was sent to acute rehabilitation. Functional Independence Measure score improved from 65 to 108. Follow-up at 6 and 10 mos showed continued improvement, with full return to his premorbid roles at home and work. The adjunct of acute rehabilitation to traditional treatment may have promoted faster recovery than expected based on previous reports. PMID- 26829079 TI - Recovery of the Corticoreticulospinal Tract Injured by a Subfalcine Herniation in a Patient with Traumatic Brain Injury. PMID- 26829080 TI - Authors' Response to a Letter to the Editor: Quadriceps Fat Pad Impingement and Synovial Hypertrophy with Mild-Moderate Lipoma Arborescens. PMID- 26829082 TI - Medial Calcaneal Neuropathy as a Cause of Intractable Heel Pain. PMID- 26829081 TI - A Preliminary Study on the Efficacy of a Community-Based Physical Activity Intervention on Physical Function-Related Risk Factors for Falls Among Breast Cancer Survivors. AB - OBJECTIVE: The aim of this study was to examine the effects of a 6-week community based physical activity (PA) intervention on physical function-related risk factors for falls among 56 breast cancer survivors (BCS) who had completed treatments. DESIGN: This was a single-group longitudinal study. The multimodal PA intervention included aerobic, strengthening, and balance components. Physical function outcomes based on the 4-meter walk, chair stand, one-leg stance, tandem walk, and dynamic muscular endurance tests were assessed at 6-week pre intervention (T1), baseline (T2), and post-intervention (T3). T1 to T2 and T2 to T3 were the control and intervention periods, respectively. RESULTS: All outcomes, except the tandem walk test, significantly improved after the intervention period (P < 0.05), with no change detected after the control period (P > 0.05). Based on the falls risk criterion in the one-leg stance test, the proportion at risk for falls was significantly lower after the intervention period (P = 0.04), but not after the control period. CONCLUSIONS: A community based multimodal PA intervention for BCS may be efficacious in improving physical function-related risk factors for falls, and lowering the proportion of BCS at risk for falls based on specific physical function-related falls criteria. Further larger trials are needed to confirm these preliminary findings. PMID- 26829083 TI - Does 6-Month Home Caregiver-Supervised Physiotherapy Improve Post-Critical Care Outcomes?: A Randomized Controlled Trial. AB - OBJECTIVE: This study aims to determine whether a 6-month home physiotherapy program can improve outcomes in critical care survivors. DESIGN: Forty-eight consecutive patients were randomized. The treatment group underwent 2 sessions/day of breathing retraining and bronchial hygiene, physical activity (mobilization, sit-to-stand gait, limb strengthening), and exercise re conditioning whereas controls underwent standard care. Maximum inspiratory/expiratory pressures (MIP/MEP), forced volumes, blood gases, dyspnea, respiratory rate, disability, peripheral force measurements, perceived health status (Euroquol-5D), patient adherence/satisfaction, safety, and costs were assessed. RESULTS: Outcomes of treatment versus controls: MIP 14 +/- 17 vs. -0.2 +/- 14 cm H2O, MEP 27 +/- 27 vs. 6 +/- 21 cm H2O both P < 0.03; in addition, quality of life (Euroquol-5D) (P = 0.04), FEV1 (P = 0.03), dyspnea (P = 0.002), and respiratory rate (P = 0.009) were significantly improved for treated cardiorespiratory patients only. Eighty-three percent of the treated patients were decannulated versus 14% of controls (P = 0.01). Compliance was high (74 +/- 25%) and there were no side effects. The majority (87.4%) expressed satisfaction with the program. Treatment cost was 459&OV0556;/patient/month. CONCLUSIONS: Carrying over regular bronchial hygiene techniques, physical activity, and exercise into the home after long critical care stays is safe and has a beneficial effect on respiratory muscles, decannulation, pulmonary function, and quality of life. PMID- 26829084 TI - Recovery From Vegetative State to Minimally Conscious State: A Case Report. AB - In this study, we attempted to demonstrate the change of the ascending reticular activating system (ARAS) concurrent with the recovery from a vegetative state (VS) to a minimally conscious state (MCS) in a patient with brain injury. A 54 year-old male patient had suffered from head trauma and underwent cardiopulmonary resuscitation immediately after head trauma. At 10 months after onset, the patient exhibited impaired consciousness, with a Coma Recovery Scale-Revised (CRS R) score of 7 (auditory function: 1, visual function: 2, motor function: 1, verbal function: 1, communication: 0, and arousal: 2) and underwent the ventriculoperitoneal shunt operation for hydrocephalus. After the operation, he began comprehensive rehabilitative therapy. At post-op 2 and 8 weeks, his CRS-R score had recovered to 15 (3/3/4/1/1/3) and 17 (3/3/4/2/2/3), respectively. In terms of configuration on diffusion tensor tractography (DTT), there was no significant change in the lower portion of the ARAS. Regarding the change of neural connectivity of the thalamic intralaminar nucleus, increased neural connectivities to the hypothalamus, basal forebrain, prefrontal cortex, anterior cingulate cortex, and parietal cortex were observed in both hemispheres on post op DTTs compared with pre-op DTT. We report on a patient with brain injury who showed change of the ARAS concurrent with the recovery from a VS and a MCS. PMID- 26829085 TI - Herpetic Brachial Plexopathy: Application of Brachial Plexus Magnetic Resonance Imaging and Ultrasound-Guided Corticosteroid Injection. AB - Herpes zoster, commonly known as shingles, is an infectious viral disease characterized by painful, unilateral skin blisters occurring in specific sensory dermatomes. Motor paresis is reported in 0.5% to 5% of patients. Although the mechanism of zoster paresis is still unclear, the virus can spread from the dorsal root ganglia to the anterior horn cell or anterior spinal nerve roots. It rarely involves the brachial plexus. We report a case of brachial plexitis following herpes zoster infection in which pathological lesions were diagnosed using brachial plexus magnetic resonance imaging and treated with ultrasound guided perineural corticosteroid injection. PMID- 26829086 TI - Postural Instability in Patients With Injury of Corticoreticular Pathway Following Mild Traumatic Brain Injury. AB - OBJECTIVE: We attempted to investigate postural instability in patients with injury of the corticoreticular pathway (CRP) after mild traumatic brain injury. METHODS: The CRP was reconstructed, and the fractional anisotropy value, apparent diffusion coefficient value, and fiber volume of the CRP were measured. For evaluation of postural instability, both the Balance Error Scoring System score and the displacement of center of pressure were measured. RESULT: Significantly lower tract volume of the CRP was observed in the patient group than in the control group with no significant difference in fractional anisotropy and apparent diffusion coefficient values(P > 0.05). The results of the Balance Error Scoring System shown on a firm and foam surface were significantly higher in the patient group than in the control group (P < 0.05). Significant increments in displacement of center of pressure for 3 stances of double-leg, single-leg, and tandem stances in distance, maximum distance, and path length were observed in the patient group compared with the control group (P < 0.05). By contrast, no significant difference in the double stance on the x axis of the distance was observed between the patient and control groups (P > 0.05). CONCLUSION: We demonstrated postural instability in patients with injury of the CRP following mild traumatic brain injury. PMID- 26829087 TI - Smartphone-Based Visual Feedback Trunk Control Training Using a Gyroscope and Mirroring Technology for Stroke Patients: Single-blinded, Randomized Clinical Trial of Efficacy and Feasibility. AB - OBJECTIVE: The purpose of this study was to assess the preliminary efficacy and feasibility of smartphone-based visual feedback trunk control training (SPVFTCT) for improving balance and trunk performance in stroke patients. DESIGN: Twenty four patients who had experienced a stroke more than 6 months previously and could sit and walk independently participated in the study. The participants were allocated to a SPVFTCT (n = 12) or to a control group (n = 12). Both groups completed five 80-minute sessions per week of conventional rehabilitation for 4 weeks. The SPVFTCT group additionally received three 20-minute sessions per week of SPVFTCT for 4 weeks. The outcome was assessed using static balance assessment, the modified functional reach test, the timed up and go test, and the trunk impairment scale. Feasibility of SPVFTCT was evaluated by retention, adherence, acceptability, and safety. RESULTS: The static balance assessment, modified functional reach test, timed up and go test, and trunk impairment scale scores in the SPVFTCT group improved significantly compared to those in the control group (P < 0.05). In the SPVFTCT group, retention and adherence rates were 100% and 97%, respectively. All participants reported that SPVFTCT was enjoyable, easy to use, and helpful for their recovery. CONCLUSIONS: The SPVFTCT approach is a feasible method to improve balance and trunk performance in stroke patients. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES:: Upon completion of this article, the reader should be able to: (1) Understand the role of trunk control in postural stability and functional improvement; (2) Describe the benefits of smartphone-based visual feedback trunk control training (SPVFTCT); and (3)Discuss the feasibility of incorporating smartphone-based visual feedback trunk control training in stroke rehabilitation. LEVEL: Advanced ACCREDITATION: : The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s). Physicians should only claim credit commensurate with the extent of their participation in the activity. PMID- 26829088 TI - Shoulder Function and Bone Mineralization in Children with Obstetric Brachial Plexus Injury After Neuromuscular Electrical Stimulation During Weight-Bearing Exercises. AB - OBJECTIVE: The purpose of this study was to evaluate the effects of neuromuscular electrical stimulation during weight-bearing exercises on shoulder function and bone mineral density (BMD) in children with obstetric brachial plexus injury (OBPI). DESIGN: This study was a randomized controlled trial. Forty-two children with OBPI were recruited. Their ages ranged from 3 to 5 years. They were randomly assigned either to control group (received a selected program) or study group (received the same program as the control group and neuromuscular electrical stimulation during weight bearing). Mallet grading system and dual-energy x-ray absorptiometry were used to evaluate shoulder function and BMD respectively at entry and after intervention (3 months later). RESULTS: No significant differences of the outcome measures were detected at entry. Significant differences were observed within both groups when the pre and post treatment scores within each group were compared. Finally, significant differences favoring the study group were recorded when their post treatment scores were compared. CONCLUSION: Neuromuscular electrical stimulation during weight bearing exercises is an effective and simple method to improve shoulder function and BMD in children with OBPI. PMID- 26829089 TI - Investigation of Biomechanical Characteristics of Intact Supraspinatus Tendons in Subacromial Impingement Syndrome: A Cross-sectional Study with Real-time Sonoelastography. AB - OBJECTIVE: The aim of this work was to evaluate the real-time sonoelastography (RTSE) in the assessment of the supraspinatus tendon in patients with subacromial impingement syndrome (SIS). METHODS: Twenty-five patients with unilateral shoulder pain that was diagnosed as SIS according to magnetic resonance imaging findings were included in the study. Healthy shoulders of the patients comprised the control group. Bilateral shoulder RTSE examinations were performed by a radiologist who was blinded to the involved side of the participants. The RTSE images were recorded and assessed by 2 radiologists individually 1 month later. American Shoulder and Elbow Surgery shoulder index, Quick Disabilities of Arm Shoulder and Hand Questionnaire, and Constant scores were applied to evaluate the disability and functional status. The correlation between strain ratio and functional scores were investigated. RESULTS: Of the 25 participants, 9 (36%) were men and 16 (64%) were women. The RTSE findings were pathologic in tendons of 23 patients (92%) with SIS. The strain ratio was significantly higher in the affected shoulders (P < 0.001). The interobserver agreement was good for image analysis. There was no significant correlation between strain ratio and functional scores. CONCLUSION: Structural changes in the supraspinatus tendon can be demonstrated with RTSE in patients with SIS. PMID- 26829090 TI - New Neural Tracts from Bilateral Fornical Columns to Compensate Bilateral Injury of Fornical Crura. PMID- 26829091 TI - Peroneus Longus Strain Injury Associated with Common Peroneal Nerve Palsy in a Soccer Player. PMID- 26829092 TI - Effect of Hospital Length of Stay on Functional Independence Measure Score in Trauma Patients. AB - OBJECTIVE: The purpose of this study was to determine whether prolonged hospital length of stay (HLOS) and rehabilitation facility length of stay (RLOS) lead to poor functional outcomes, defined as a Functional Independence Measure (FIM) score of less than 76 (LFIM) at rehabilitation facility (RF) discharge. DESIGN: This study analyzed retrospective data collected between 2002 and 2009 on 326 patients in a trauma center and affiliated RF. Factors predicting LFIM at RF discharge were determined using multivariate logistic regression, chi tests, and t tests. RESULTS: Significant multivariate predictors of LFIM included age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.02-1.07; P < 0.0001), spinal cord injury (OR, 7.22; 95% CI, 2.73-19.02; P = 0.000), female sex (OR, 2.34; 95% CI, 1.17-4.65; P = 0.01), and RF admission FIM (OR, 0.93; 95% CI, 0.91-0.95; P < 0.001). An increased risk of LFIM (OR, 2.21; 95% CI, 1.41-3.45; P = 0.001) was observed with an increased ratio of HLOS/RLOS after adjusting for injury severity score. CONCLUSION: An increased ratio of HLOS/RLOS increases the risk of LFIM more than 2-fold after adjusting for injury severity score, spinal cord injury, and FIM upon RF admission. Delays in transfer to an RF negatively affect patient functional outcomes. Studies to identify factors affecting delays in transfer from hospitals to RF should be conducted. PMID- 26829094 TI - Short-Term Effects of Whole-Body Vibration Combined with Task-Related Training on Upper Extremity Function, Spasticity, and Grip Strength in Subjects with Poststroke Hemiplegia: A Pilot Randomized Controlled Trial. AB - OBJECTIVE: The aim of this study was to determine the effect of whole-body vibration training combined with task-related training on arm function, spasticity, and grip strength in subjects with poststroke hemiplegia. DESIGN: Forty-five subjects with poststroke were randomly allocated to 3 groups, each with 15 subjects as follows: control group, whole-body vibration group, and whole body vibration plus task-related training group. Outcome was evaluated by clinical evaluation and measurements of the grip strength before and 4 weeks after intervention. RESULTS: Our results show that there was a significantly greater increase in the Fugl-Meyer scale, maximal grip strength of the affected hand, and grip strength normalized to the less affected hand in subjects undergoing the whole-body vibration training compared with the control group after the test. Furthermore, there was a significantly greater increase in the Wolf motor function test and a decrease in the modified Ashworth spasticity total scores in subjects who underwent whole-body vibration plus task-related training compared with those in the other 2 groups after the test. CONCLUSIONS: The findings indicate that the use of whole-body vibration training combined with task-related training has more benefits on the improvement of arm function, spasticity, and maximal grip strength than conventional upper limb training alone or with whole-body vibration in people with poststroke hemiplegia. PMID- 26829093 TI - Predictors of Altered Upper Extremity Function During the First Year After Breast Cancer Treatment. AB - OBJECTIVE: The purpose of this study was to evaluate trajectories of and predictors for changes in upper extremity (UE) function in women (n = 396) during the first year after breast cancer treatment. DESIGN: Prospective, longitudinal assessments of shoulder range of motion (ROM), grip strength, and perceived interference of function were performed before and for 1 year after surgery. Demographic, clinical, and treatment characteristics were evaluated as predictors of postoperative function. RESULTS: Women had a mean (SD) age of 54.9 (11.6) years, and 64% were white. Small but statistically significant reductions in shoulder ROM were found on the affected side over 12 months (P < 0.001). Predictors of interindividual differences in ROM at the 1-month assessment were ethnicity, neoadjuvant chemotherapy, type of surgery, axillary lymph node dissection, and preoperative ROM. Predictors of interindividual differences in changes over time in postoperative ROM were living alone, type of surgery, axillary lymph node dissection, and adjuvant chemotherapy. Declines in mean grip strength from before through 1 month after surgery were small and not clinically meaningful. Women with greater preoperative breast pain interference scores had higher postoperative interference scores at all postoperative assessments. CONCLUSION: Some of the modifiable risk factors identified in this study can be targeted for intervention to improve UE function in these women. PMID- 26829095 TI - Rehabilitation Nutrition for Possible Sarcopenic Dysphagia After Lung Cancer Surgery: A Case Report. AB - Sarcopenic dysphagia is characterized by the loss of swallowing muscle mass and function associated with generalized loss of skeletal muscle mass and function. In this report, the authors describe a patient with possible sarcopenic dysphagia after lung cancer surgery and was treated subsequently by rehabilitation nutrition. A 71-year-old man with lung cancer experienced complications of an acute myocardial infarction and pneumonia after surgery. He was ventilated artificially, and a tracheotomy was performed. The patient received diagnoses of malnutrition, severe sarcopenia, and possible sarcopenic dysphagia. His dysphagia was improved by a combination of dysphagia rehabilitation including physical and speech therapy and an improvement in nutrition initiated by a nutrition support team. Finally, he no longer had dysphagia and malnutrition. Sarcopenic dysphagia should be considered in patients with sarcopenia and dysphagia. Rehabilitation nutrition using a combination of both rehabilitation and nutritional care management is presumptively useful for treating sarcopenic dysphagia. PMID- 26829096 TI - The "Profiles" profile: "a change in the [medical] teaching and learning paradigm" hopefully scrutinised in the future. PMID- 26829097 TI - UV-Vis Ratiometric Resonance Synchronous Spectroscopy for Determination of Nanoparticle and Molecular Optical Cross Sections. AB - Demonstrated herein is a UV-vis Ratiometric Resonance Synchronous Spectroscopic (R2S2, pronounced as "R-two-S-two" for simplicity) technique where the R2S2 spectrum is obtained by dividing the resonance synchronous spectrum of a NP containing solution by the solvent resonance synchronous spectrum. Combined with conventional UV-vis measurements, this R2S2 method enables experimental quantification of the absolute optical cross sections for a wide range of molecular and nanoparticle (NP) materials that range optically from pure photon absorbers or scatterers to simultaneous photon absorbers and scatterers, simultaneous photon absorbers and emitters, and all the way to simultaneous photon absorbers, scatterers, and emitters in the UV-vis wavelength region. Example applications of this R2S2 method were demonstrated for quantifying the Rayleigh scattering cross sections of solvents including water and toluene, absorption and resonance light scattering cross sections for plasmonic gold nanoparticles, and absorption, scattering, and on-resonance fluorescence cross sections for semiconductor quantum dots (Qdots). On-resonance fluorescence quantum yields were quantified for the model molecular fluorophore Eosin Y and fluorescent Qdots CdSe and CdSe/ZnS. The insights and methodology presented in this work should be of broad significance in physical and biological science research that involves photon/matter interactions. PMID- 26829098 TI - Experimental investigation to evaluate the potential environmental hazards of photovoltaic panels. AB - Recently the potential environmental hazard of photovoltaic modules together with their management as waste has attracted the attention of scientists. Particular concern is aroused by the several metals contained in photovoltaic panels whose potential release in the environment were scarcely investigated. Here, for the first time, the potential environmental hazard of panels produced in the last 30 years was investigated through the assessment of up to 18 releasable metals. Besides, the corresponding ecotoxicological effects were also evaluated. Experimental data were compared with the current European and Italian law limits for drinking water, discharge on soil and landfill inert disposal in order to understand the actual pollution load. Results showed that less than 3% of the samples respected all law limits and around 21% was not ecotoxic. By considering the technological evolutions in manufacturing, we have shown that during the years crystalline silicon panels have lower tendency to release hazardous metals with respect to thin film panels. In addition, a prediction of the amounts of lead, chromium, cadmium and nickel releasable from next photovoltaic waste was performed. The prevision up to 2050 showed high amounts of lead (30t) and cadmium (2.9t) releasable from crystalline and thin film panels respectively. PMID- 26829099 TI - Restoring anti-tumor functions of T cells via nanoparticle-mediated immune checkpoint modulation. AB - The core purpose of cancer immunotherapy is the sustained activation and expansion of the tumor specific T cells, especially tumor-infiltrating cytotoxic T lymphocytes (CTLs). Currently, one of the main foci of immunotherapy involving nano-sized carriers is on cancer vaccines and the role of professional antigen presenting cells, such as dendritic cells (DCs) and other phagocytic immune cells. Besides the idea that cancer vaccines promote T cell immune responses, targeting immune inhibitory pathways with nanoparticle delivered regulatory agents such as small interfering RNA (siRNA) to the difficultly-transfected tumor infiltrating T cells may provide more information on the utility of nanoparticle mediated cancer immunotherapy. In this study, we constructed nanoparticles to deliver cytotoxic T lymphocyte-associated molecule-4 (CTLA-4)-siRNA (NPsiCTLA-4) and showed the ability of this siRNA delivery system to enter T cells both in vitro and in vivo. Furthermore, T cell activation and proliferation were enhanced after NPsiCTLA-4 treatment in vitro. The ability of direct regulation of T cells of this CTLA-4 delivery system was assessed in a mouse model bearing B16 melanoma. Our results demonstrated that this nanoparticle delivery system was able to deliver CTLA-4-siRNA into both CD4(+) and CD8(+) T cell subsets at tumor sites and significantly increased the percentage of anti-tumor CD8(+) T cells, while it decreased the ratio of inhibitory T regulatory cells (Tregs) among tumor infiltrating lymphocytes (TILs), resulting in augmented activation and anti-tumor immune responses of the tumor-infiltrating T cells. These data support the use of potent nanoparticle-based cancer immunotherapy for melanoma. PMID- 26829100 TI - Lauroyl-gemcitabine-loaded lipid nanocapsule hydrogel for the treatment of glioblastoma. AB - The local delivery of chemotherapeutic agents is a very promising strategy for the treatment of glioblastoma (GBM). Gemcitabine is a chemotherapeutic agent that has a different mechanism of action compared to alkylating agents and shows excellent radio-sensitizing properties. So, we developed an injectable gel-like nanodelivery system consisting in lipid nanocapsules loaded with anticancer prodrug lauroyl-gemcitabine (GemC12-LNC) in order to obtain a sustained and local delivery of this drug in the brain. In this study, the GemC12-LNC has been formulated and characterized and the viscoelastic properties of the hydrogel were evaluated after extrusion from 30G needles. This system showed a sustained and prolonged in vitro release of the drug over one month. GemC12 and the GemC12-LNC have shown increased in vitro cytotoxic activity on U-87 MG glioma cells compared to the parent hydrophilic drug. The GemC12-LNC hydrogel reduced significantly the size of a subcutaneous human GBM tumor model compared to the drug and short-term tolerability studies showed that this system is suitable for local treatment in the brain. In conclusion, this proof-of-concept study demonstrated the feasibility, safety and efficiency of the injectable GemC12-LNC hydrogel for the local treatment of GBM. PMID- 26829101 TI - Reformulating cyclosporine A (CsA): More than just a life cycle management strategy. AB - Cyclosporine A (CsA) is a well-known immunosuppressive agent that gained considerable importance in transplant medicine in the late 1970s due to its selective and reversible inhibition of T-lymphocytes. While CsA has been widely used to prevent graft rejection in patients undergoing organ transplant it was also used to treat several systemic and local autoimmune disorders. Currently, the neuro- and cardio-protective effects of CsA (CiCloMulsion(r); NeuroSTAT(r)) are being tested in phase II and III trials respectively and NeuroSTAT(r) received orphan drug status from US FDA and Europe in 2010. The reformulation strategies focused on developing Cremophor(r) EL free formulations and address variable bioavailability and toxicity issues of CsA. This review is an attempt to highlight the progress made so far and the room available for further improvements to realize the maximum benefits of CsA. PMID- 26829102 TI - Micropore closure kinetics are delayed following microneedle insertion in elderly subjects. AB - Transdermal delivery is an advantageous method of drug administration, particularly for an elderly population. Microneedles (MNs) allow transdermal delivery of otherwise skin-impermeable drugs by creating transient micropores that bypass the barrier function of the skin. The response of aging skin to MNs has not been explored, and we report for the first time that micropore closure is delayed in elderly subjects in a manner that is dependent upon MN length, number, and occlusion of the micropores. Twelve control subjects (25.6+/-2.8years) and 16 elderly subjects (77.3+/-6.8years) completed the study. Subjects were treated with MNs of 500MUm or 750MUm length, in arrays containing 10 or 50 MNs. Impedance measurements made at baseline, post-MN insertion, and at predetermined time points demonstrated that restoration of the skin barrier is significantly slower in elderly subjects under both occluded and non-occluded conditions. This was confirmed via calculation of the total permeable area created by the micropores (which would approximate the area available for drug delivery), as well as calculation of the micropore half-life. This pilot study demonstrates that longer timeframes are required to restore the barrier function of aged skin following MN insertion, suggesting that drug delivery windows could be longer following one treatment with a MN array. PMID- 26829104 TI - Photoheat-induced Schottky nanojunction and indirect Mott transition in VO2: photocurrent analysis. AB - In order to elucidate a mechanism of the insulator-to-metal transition (IMT) for a Mott insulator VO2 (3d(1)), we present Schottky nanojunctions and the structural phase transition (SPT) by simultaneous nanolevel measurements of photocurrent and Raman scattering in microlevel devices. The Schottky nanojunction with the monoclinic metallic phase between the monoclinic insulating phases is formed by the photoheat-induced IMT not accompanied with the SPT. The temperature dependence of the Schottky junction reveals that the Mott insulator has an electronic structure of an indirect subband between the main Hubbard d bands. The IMT as reverse process of the Mott transition occurs by temperature induced excitation of bound charges in the indirect semiconductor band, most likely formed by impurities such as oxygen deficiency. The metal band (3d(1)) for the Mott insulator is screened (trapped) by the indirect band (impurities). PMID- 26829103 TI - The application of local hypobaric pressure - A novel means to enhance macromolecule entry into the skin. AB - The local application of controlled hypobaric stress represents a novel means to facilitate drug delivery into the skin. The aims of this work were to understand how hypobaric stress modified the properties of the skin and assess if this penetration enhancement strategy could improve the percutaneous penetration of a macromolecule. Measurements of skin thickness demonstrated that the topical application of hypobaric stress thinned the tissue (p<0.05), atomic force microscopy showed that it shrunk the corneocytes in the stratum corneum (p<0.001) and the imaging of the skin hair follicles using multiphoton microscopy showed that it opened the follicular infundibula (p<0.001). Together, these changes contributed to a 19.6-fold increase in in vitro percutaneous penetration of a 10,000 molecular weight dextran molecule, which was shown using fluorescence microscopy to be localized around the hair follicles, when applied to the skin using hypobaric stress. In vivo, in the rat, a local hemodynamic response (i.e. a significant increase in blood flow, p<0.001) was shown to contribute to the increase in follicular transport of the dextran to produce a systemic absorption of 7.2+/-2.81fg.mL(-1). When hypobaric stress was not applied to the rat there was no detectable absorption of dextran and this provided evidence that this novel penetration enhancement technique can improve the percutaneous penetration of macromolecules after topical application to the skin. PMID- 26829105 TI - Visible-Light-Induced Alkoxyl Radical Generation Enables Selective C(sp(3)) C(sp(3)) Bond Cleavage and Functionalizations. AB - The alkoxyl radical is an important reactive intermediate in mechanistic studies and organic synthesis; however, its current generation from alcohol oxidation heavily relies on transition metal activation under strong oxidative conditions. Here we report the first visible-light-induced alcohol oxidation to generate alkoxyl radicals by cyclic iodine(III) reagent catalysis under mild reaction conditions. The beta-fragmentation of alkoxyl radicals enables selective C(sp(3)) C(sp(3)) bond cleavage and alkynylation/alkenylation reactions with various strained cycloalkanols, and for the first time with linear alcohols. PMID- 26829106 TI - Design, synthesis, and antimicrobial activities of new tanshinone IIA esters. AB - Sixteen new ester derivatives with various partition coefficient (ClogP) values of tanshinone IIA (TSIIA), a major lipophilic component of Salvia miltiorrhiza, were designed and synthesised, including six aliphatic esters (3a-e, 5a), one phosphate ester (4c) and nine aromatic esters (5b-j). Their antimicrobial activities against three Gram-positive bacteria strains, Staphylococcus aureus, Bacillus subtilis, and Bacillus amyloliquefaciens, and two Gram-negative bacteria strains, Pseudomonas aeruginosa and Escherichia coli, as well as two fungi species, Candida albicans and Saccharomyces cerevisiae, were evaluated in vitro by broth microdilution susceptibility tests. The results showed that keeping ClogP values in a certain range is necessary for their antimicrobial activities. For those compounds with ClogP values between 5 and 10, their MIC values showed positive correlations with ClogP values. In particular, compound 3e exhibited fourfold and twofold higher potency than the standard drug amphotericin B against fungi C. albicans and S. cerevisiae with MIC values of 1.95 and 7.81 MUg/mL, respectively. PMID- 26829107 TI - Expansion of CD8+ cells in autoimmune hemolytic anemia. AB - Autoimmune hemolytic anemia (AIHA) is a rare blood disease associated with the production of auto-antibodies and autoimmune hemolysis. A critical role of B cells in the development of AIHA has been demonstrated before. Here, we present the analysis of the clonal T-cell populations in patients with AIHA. Thirty-three patients with AIHA were included in this study. Thirteen patients with other anemias, 14 patients with other autoimmune conditions (SLE - 6, RA - 8) and 20 healthy donors were included in the study as a control group. The clonality of T cell was evaluated by the assessment of the T-cell receptor gamma and beta chain gene rearrangements (TCRG and TCRB). The incidence of T-cell monoclonality detected in patients with AIHA was significantly higher compared to the control group. The persistence of T-cell clones did not correlate with the level of hemoglobin and other signs of remission or relapse and did not disappear after the therapy and clinical improvement (observation period was between 1 and 10 years). There was no correlation between the T-cell clonality and the gender, age, splenectomy, duration or severity of the disease. Fractionation of T lymphocytes (CD4+, CD8+, CD4+25+) revealed that the monoclonal T-cells belonged to the CD8+ sub-population. We assume that besides a possible causative role of the T-cell clones in AIHA to autoimmune process, these clones do not directly participate in the development and maintenance of hemolysis. Most of the AIHA patients (48.5%) demonstrated a T-cell monoclonality, which requires monitoring and should be distinguished from T-cell tumors. PMID- 26829108 TI - Estrogen-Receptor, Progesterone-Receptor and HER2 Status Determination in Invasive Breast Cancer. Concordance between Immuno-Histochemistry and MapQuantTM Microarray Based Assay. AB - BACKGROUND: Hormone receptor status and HER2 status are of critical interest in determining the prognosis of breast cancer patients. Their status is routinely assessed by immunohistochemistry (IHC). However, it is subject to intra laboratory and inter-laboratory variability. The aim of our study was to compare the estrogen receptor, progesterone receptor and HER2 status as determined by the MapQuantTM test to the routine immuno-histochemical tests in early stage invasive breast cancer in a large comprehensive cancer center. PATIENTS AND METHODS: We retrospectively studied 163 invasive early-stage breast carcinoma with standard IHC status. The genomic status was determined using the MapQuantTM test providing the genomic grade index. RESULTS: We found only 4 tumours out of 161 (2.5%) with discrepant IHC and genomic results concerning ER status. The concordance rate between the two methods was 97.5% and the Cohen's Kappa coefficient was 0.89. Comparison between the MapQuantTM PR status and the PR IHC status gave more discrepancies. The concordance rate between the two methods was 91.4% and the Cohen's Kappa coefficient was 0.74. The HER2 MapQuantTM test was classified as " undetermined " in 2 out of 163 cases (1.2%). One HER2 IHC-negative tumour was found positive with a high HER2 MapQuantTM genomic score. The concordance rate between the two methods was 99.3% and the Cohen's Kappa coefficient was 0.86. CONCLUSION: Our results show that the MapQuantTM assay, based on mRNA expression assay, provides an objective and quantitative assessment of Estrogen receptor, Progesterone receptor and HER2 status in invasive breast cancer. PMID- 26829110 TI - Repeated low-dose exposures to sarin, soman, or VX affect acoustic startle in guinea pigs. AB - Chemical warfare nerve agents (CWNAs) are known to cause behavioral abnormalities in cases of human exposures and in animal models. The behavioral consequences of single exposures to CWNAs that cause observable toxic signs are particularly well characterized in animals; however, less is known regarding repeated smaller exposures that may or may not cause observable toxic signs. In the current study, guinea pigs were exposed to fractions (0.1, 0.2, or 0.4) of a medial lethal dose (LD50) of sarin, soman, or VX for two weeks. On each exposure day, and for a post exposure period, acoustic startle response (ASR) was measured in each animal. Although relatively few studies use guinea pigs to measure behavior, this species is ideal for CWNA-related experiments because their levels of carboxylesterases closely mimic those of humans, unlike rats or mice. Results showed that the 0.4 LD50 doses of soman and VX transiently increased peak startle amplitude by the second week of injections, with amplitude returning to baseline by the second week post-exposure. Sarin also increased peak startle amplitude independent of week. Latencies to peak startle and PPI were affected by agent exposure but not consistently among the three agents. Most of the changes in startle responses returned to baseline following the cessation of exposures. These data suggest that doses of CWNAs not known to produce observable toxic signs in guinea pigs can affect behavior in the ASR paradigm. Further, these deficits are transient and usually return to baseline shortly after the end of a two-week exposure period. PMID- 26829109 TI - MPX-004 and MPX-007: New Pharmacological Tools to Study the Physiology of NMDA Receptors Containing the GluN2A Subunit. AB - GluN2A is the most abundant of the GluN2 NMDA receptor subunits in the mammalian CNS. Physiological and genetic evidence implicate GluN2A-containing receptors in susceptibility to autism, schizophrenia, childhood epilepsy and neurodevelopmental disorders such as Rett Syndrome. However, GluN2A-selective pharmacological probes to explore the therapeutic potential of targeting these receptors have been lacking. Here we disclose a novel series of pyrazine containing GluN2A antagonists exemplified by MPX-004 (5-(((3-chloro-4 fluorophenyl)sulfonamido)methyl)-N-((2-methylthiazol-5-yl)methyl)pyrazine-2 carboxamide) and MPX-007 (5-(((3-fluoro-4-fluorophenyl)sulfonamido)methyl)-N-((2 methylthiazol-5-yl)methyl)methylpyrazine-2-carboxamide). MPX-004 and MPX-007 inhibit GluN2A-containing NMDA receptors expressed in HEK cells with IC50s of 79 nM and 27 nM, respectively. In contrast, at concentrations that completely inhibited GluN2A activity these compounds have no inhibitory effect on GluN2B or GluN2D receptor-mediated responses in similar HEK cell-based assays. Potency and selectivity were confirmed in electrophysiology assays in Xenopus oocytes expressing GluN2A-D receptor subtypes. Maximal concentrations of MPX-004 and MPX 007 inhibited ~30% of the whole-cell current in rat pyramidal neurons in primary culture and MPX-004 inhibited ~60% of the total NMDA receptor-mediated EPSP in rat hippocampal slices. GluN2A-selectivity at native receptors was confirmed by the finding that MPX-004 had no inhibitory effect on NMDA receptor mediated synaptic currents in cortical slices from GRIN2A knock out mice. Thus, MPX-004 and MPX-007 offer highly selective pharmacological tools to probe GluN2A physiology and involvement in neuropsychiatric and developmental disorders. PMID- 26829111 TI - Expression and purification of recombinant H5HA1 protein of H5N1 avian influenza virus in E. coli and its application in indirect ELISA. AB - The PCR amplified HA1 fragment of H5N1 (H5HA1) avian influenza virus (AIV) hemagglutinin gene was cloned into pET28a (+) expression vector and expressed in Rosetta Blue (DE3) pLysS cells. The recombinant H5HA1 (rH5HA1) protein purified by passive gel elution after SDS-PAGE of the inclusion bodies reacted specifically with H5N1 serum in Western blot analysis. A subtype specific indirect enzyme linked immunosorbent assay (iELISA) using the rH5HA1 protein as the coating antigen was developed for detecting antibodies to H5 subtype of AIV. The assay had 89.04% sensitivity and 95.95% specificity when compared with haemagglutination inhibition test. The Kappa value of 0.842 indicated a perfect agreement between the tests. The iELISA developed can be used for serosurveillance of avian influenza in chickens. PMID- 26829112 TI - Prolonged repolarization in atrial septal defect: An example of mechanoelectrical feedback due to right ventricular volume overload. AB - BACKGROUND: Prolonged corrected QT (QTc) intervals are frequently observed in children before atrial septal defect (ASD) closure in our department. OBJECTIVE: The aim of the study was to assess the effect of long-term right ventricular volume overload on repolarization. METHODS: QRS, QT, and JT intervals were measured manually in leads II and V5 of a standard 12-lead electrocardiogram in 45 children with an isolated ASD a day before and at least 6 months after ASD closure. QT intervals were corrected for heart rate using the Bazett, Fridericia, Framingham, and Hodges formulas. Each QTc interval calculated using the Bazett formula was compared to sex- and age-matched normal values. RESULTS: Individual QTc intervals shortened significantly (P < .001) using all correction formulas, whereas the QRS duration did not change. The prevalence of prolonged QTc interval decreased from 22.2% to 2.2% after shunt closure (P = .007). CONCLUSION: The QTc interval shortens significantly after the closure of a hemodynamically relevant ASD in childhood. This phenomenon is independent of the used QT correction formula and may reflect a mechanoelectrical feedback associated with right ventricular volume overload. PMID- 26829113 TI - Predictors and clinical relevance of ventricular tachyarrhythmias in ambulatory patients with a continuous flow left ventricular assist device. AB - BACKGROUND: Patients with a left ventricular assist device (LVAD) are at high risk for ventricular tachyarrhythmias (VTAs). OBJECTIVE: We aimed to identify clinical predictors of VTAs and subsequent outcomes after VTA in ambulatory LVAD patients. METHODS: A retrospective study of 149 patients with a continuous flow HeartMate II LVAD who survived to discharge from index hospitalization after LVAD implantation was performed from January 10, 2005, to September 3, 2013. A multivariate Cox model was used to assess clinical predictors of VTAs. RESULTS: During a mean follow-up period of 2.1 +/- 1.2 years, 41 patients (28%) experienced VTAs; 30 of these patients (71%) had ventricular tachycardia, and 11 (29%) had ventricular fibrillation. History of VTAs before LVAD (hazard ratio [HR] 3.06; 95% confidence interval [CI] 1.57-5.96; P = .001) and history of atrial fibrillation (AF) (HR 3.13; 95% CI 1.60-6.11; P = .008) were the most powerful predictors of VTAs after LVAD implantation. There were 19 deaths (46%) among patients with VTAs and 15 deaths (14%) among patients without VTAs (P < .001). In multivariate analysis, time-dependent VTAs after LVAD implantation were associated with a significantly higher risk of all-cause mortality when compared with those without VTAs (HR 7.28; 95% CI 3.50-15.15; P < .001). CONCLUSION: In ambulatory LVAD patients, history of VTAs before LVAD implantation and history of AF predict VTAs after LVAD implantation. VTAs are associated with an increased risk of mortality. In such patients, aggressive measures to control VTAs and AF should be considered. PMID- 26829114 TI - Extraction of chronically implanted coronary sinus leads active fixation vs passive fixation leads. AB - BACKGROUND: The Medtronic model 4195 (StarFix) left ventricular lead is an active fixation lead that provides additional support within the coronary sinus (CS) via deployable lobes. While this lead has been shown to have excellent stability within the CS, concerns about its extractability have been raised. OBJECTIVE: The aim of this study was to compare the safety and efficacy of the extraction of the model 4195 lead vs other Medtronic CS leads in a prospective cohort study. METHODS: Patients undergoing extraction of this and other CS leads for standard indications were prospectively enrolled and studied. The primary outcomes of interest were the removal success rates and associated complication rates. Patients were followed for a month postprocedure. RESULTS: The overall left ventricular lead extraction success rate was 97.6% (n = 205). Among 40 patients with chronic model 4195 leads, there were 37 successful extractions (92.5%) as compared to 98.8% for the 165 non-4195 leads. However, in 2 of the 3 StarFix lead extraction failures, standard extraction techniques were not used. All 10 of the model 4195 leads that had been implanted for less than 6 months were extracted without incident. CONCLUSION: In this largest study of CS lead extractions published to date, the overall success rate of the extraction of chronically implanted CS leads is high and the complication rate is similar in these lead models. The extraction of the model 4195 lead is clearly more challenging, but it can be accomplished in high-volume extraction centers with experienced operators. It is recommended that the model 4195 lead be extracted by experienced operators. PMID- 26829115 TI - High-dose flecainide is the most effective treatment of fetal supraventricular tachycardia. AB - BACKGROUND: Fetal tachyarrhythmia can lead to fetal hydrops due to heart failure. Flecainide is often considered as second-line therapy when digoxin monotherapy fails, which is more likely in hydropic fetuses. Time to conversion to sinus rhythm (SR) is critical in cases presenting with hydrops. OBJECTIVE: The aim of this study was to evaluate the efficacy and time to conversion to SR of transplacental treatment, especially flecainide. METHODS: This is a retrospective observational study of 46 fetuses with fetal tachyarrhythmia. Treatment was either flecainide (n = 28, 60.9%), digoxin+flecainide combination (n = 4, 8.7%), or digoxin (n = 10, 21.7%). In 4 fetuses (8.7%), no treatment was necessary. RESULTS: In our study population, 26 of the 32 fetuses (81.2%) that were treated with flecainide as a first-line therapy (flecainide or digoxin+flecainide) converted to SR. The median time to conversion to SR was 3 days (range 1-7 days) with flecainide monotherapy and 11.5 days (range 3-14 days) with a combination therapy. Seventy-two percent (13/18) of hydropic fetuses and 90% (9/10) of nonhydropic fetuses converted to SR when treated with flecainide monotherapy. There was no statistical difference in rates of conversion to SR in hydropic and nonhydropic fetuses (P = .37) or time to conversion to SR in the 2 groups (P = .9). In the majority of the remaining fetuses, there was a partial response with decreased ventricular heart rates that were well tolerated. CONCLUSION: Flecainide is highly effective in achieving SR in hydropic and nonhydropic fetuses with supraventricular tachycardia in a median time of 3 days. In our opinion, flecainide should be considered as first-line therapy in fetal supraventricular tachycardia with and without hydrops. PMID- 26829116 TI - The effect of electrode density on the interpretation of atrial activation patterns in epicardial mapping of human persistent atrial fibrillation. AB - BACKGROUND: Mechanisms sustaining human persistent atrial fibrillation (AF) remain debated, with significant differences between high-density epicardial and global endocardial mapping studies. A key difference is the density of recording electrodes. OBJECTIVE: We aimed to determine the differences in the prevalence of different atrial activation patterns, and specifically in the prevalence of rotational activations, with varying densities of bipolar electrodes. METHODS: Epicardial mapping was performed in 10 patients undergoing cardiac surgery, with bipolar electrograms recorded using a triangular plaque (6.75 cm(2) area; 117 bipoles; 2.5-mm inter-bipole spacing) applied to the left atrial posterior wall or right atrial free wall. Dynamic wavefront mapping based on the timing of atrial electrograms was applied to 2 discrete 10-second AF segments. The spacing between bipolar electrode locations was increased from 2.5 * 3.5 mm in the horizontal and oblique directions to 5.0 * 3.5, 5.0 * 7.1, and 7.5 * 10.6 mm, with wavefront mapping repeated at each density. RESULTS: As density reduced, there was a significant change in relative proportions of the various activation patterns (F=3.69; P < .001). Simple broad wavefront activations became more prevalent (20% +/- 8% to 54% +/- 8%; P < .05) and complex patterns became less prevalent (48% +/- 8% to 9% +/- 8%; P < .05) with reducing density. The prevalence of rotational activity declined with bipole density, from median 5.0% (range 0.9%-12.1%) to 0% (range 0%-1.5%) (P = .03). The largest change occurred between inter-bipole spacings of 5.0 * 3.5 and 5.0 * 7.1 mm. CONCLUSION: Apparent activation patterns in persistent AF vary significantly with electrode density. Low density underestimates the prevalence of complex and rotational patterns. The largest difference occurs between an inter-bipole spacing of 5.0 * 3.5 and a spacing of 5.0 * 7.1 mm. This may have important implications for mapping technology design. PMID- 26829118 TI - Novel molecular mechanisms and regeneration therapy for heart failure. AB - Heart failure (HF) is one of the leading causes of mortality in the world. Various molecular mechanisms have been proposed for HF, but its precise mechanisms are still largely unknown. In this review, summarizing the "President's Distinguished Lecture Award" of XX World Congress of International Society for Heart Research 2010 in Kyoto, Japan, we introduce recent our studies on HF, including 1) p53-induced suppression of Hif-1-induced angiogenesis as a novel mechanism of HF, 2) angiogenesis as a potential therapeutic strategy for HF, and 3) IGFBP-4 as a novel factor for cardiomyogenesis by inhibiting canonical Wnt signaling. PMID- 26829119 TI - Strokes or Seizures, and Takotsubo Syndrome: A Possibly Underdiagnosed Association. PMID- 26829117 TI - "Canonical and non-canonical actions of GRK5 in the heart". AB - As the average world-wide lifespan continues to increase, heart failure (HF) has dramatically increased in incidence leading to the highest degree of mortality and morbidity of any disease presently studied. G protein-coupled receptors (GPCRs) play a prominent role in regulation of cardiovascular function. GPCRs are effectively "turned off" by GPCR kinases (GRKs) in a process known as "desensitization". GRKs 2 and 5 are highly expressed in the heart, and known to be upregulated in HF. Over the last 20years, the role of GRK2 in HF has been widely studied. However, until recently, the role of GRK5 in cardiac pathophysiology had yet to be elucidated. In the present review, we will focus on GRK5's role in the myocardium in normal physiology, and its apparent critical role in the progression of HF. Further, we will also present potential therapeutic strategies (i.e. small molecule inhibition, gene therapy) that may have potential in combating the deleterious effects of GRK5 in HF. PMID- 26829120 TI - Nuclear Multidrug Resistance-Related Protein 1 Is Highly Associated with Better Prognosis of Human Mucoepidermoid Carcinoma through the Suppression of Cell Proliferation, Migration and Invasion. AB - OBJECTIVES: Multidrug resistance-related protein 1 (MRP1) overexpression is a well acknowledged predictor of poor response to chemotherapy, but MRP1 also correlated to better prognosis in some reports, especially for patients not pretreated with chemotherapy. In our previous study, we found nuclear translocation of MRP1 in mucoepidermoid carcinoma (MEC) for the first time. The purpose of this study was to further investigate the function of nuclear MRP1 in MEC. MATERIALS AND METHODS: Human MEC tissue samples of 125 patients were selected and stained using immunohistochemistry. The expression level of total MRP1/nuclear MRP1 of each sample was evaluated by expression index (EI) which was scored using both qualitative and quantitative analysis. The correlations between the clinicopathologic parameters and the EI of nuclear MRP1 were analyzed using Spearman's rank correlation analysis, respectively. The effects of RNAi-mediated downregulation of nuclear MRP1 on MEC cells were assessed using flow cytometric analysis, MTT assay, plate colony formation assay, transwell invasion assay and monolayer wound healing assay. RESULTS: In this study, we found the EI of nuclear MRP1 was negatively correlated to the pathologic grading (r = -0.498, P<0.01)/clinical staging (r = -0.41, P<0.01)/tumor stage (r = -0.28, P = 0.02)/nodal stage (r = -0.29, P<0.01) of MEC patients. The RNAi-mediated downregulation of nuclear MRP1 further proved that the downregulation of nuclear MRP1 could increase the cell replication, growth speed, colony formation efficiency, migration and invasion ability of MEC cells. CONCLUSION: Our results suggested that nuclear MRP1 is highly associated with better prognosis of human mucoepidermoid carcinoma and further study of its function mechanism would provide clues in developing new treatment modalities of MEC. PMID- 26829122 TI - Multifactorial theory applied to the neurotoxicity of paraquat and paraquat induced mechanisms of developing Parkinson's disease. AB - Laboratory studies involving repeated exposure to paraquat (PQ) in different animal models can induce many of the pathological features of Parkinson's disease (PD), such as the loss of dopaminergic neurons in the nigrostriatal dopamine system. Epidemiological studies identify an increased risk of developing PD in human populations living in areas where PQ exposure is likely to occur and among workers lacking appropriate protective equipment. The mechanisms involved in developing PD may not be due to any single cause, but rather a multifactorial situation may exist where PQ exposure may cause PD in some circumstances. Multifactorial theory is adopted into this review that includes a number of sub cellular mechanisms to explain the pathogenesis of PD. The theory is placed into an environmental context of chronic low-dose exposure to PQ that consequently acts as an oxidative stress inducer. Oxidative stress and the metabolic processes of PQ-inducing excitotoxicity, alpha-synuclein aggregate formation, autophagy, alteration of dopamine catabolism, and inactivation of tyrosine hydroxylase are positioned as causes for the loss of dopaminergic cells. The environmental context and biochemistry of PQ in soils, water, and organisms is also reviewed to identify potential routes that can lead to chronic rates of low-dose exposure that would replicate the type of response that is observed in animal models, epidemiological studies, and other types of laboratory investigations involving PQ exposure. The purpose of this review is to synthesize key relations and summarize hypotheses linking PD to PQ exposure by using the multifactorial approach. Recommendations are given to integrate laboratory methods to the environmental context as a means to improve on experimental design. The multifactorial approach is necessary for conducting valid tests of causal relations, for understanding of potential relations between PD and PQ exposure, and may prevent further delay in solving what has proven to be an evasive etiological problem. PMID- 26829123 TI - Removal of pollutants by enhanced coagulation combined PAC with variable charge soils: flocs' properties and effect of pH. AB - This study investigated the properties of flocs and effects of the solution pH on removal of representative pollutants by enhanced coagulation with variable charge soils of South China and polyaluminum chloride (PAC). The results demonstrated that the removal efficiency of turbidity was larger and the aggregated flocs had a faster growth rate, bigger size, denser structure and faster settling rate than those generated by PAC alone, when variable charge soil was used in conjunction with PAC. Additionally, initial solutions pH had meaningful effects on removal of pollutants. With the increase in the pH of the solution, the removal efficiencies of turbidity, algae and heavy metal ions significantly increased. Besides, charge neutralization together with physical entrapment of colloids was the dominant mechanism in enhanced coagulation, and variable charge soil displayed a great adsorption effect. PMID- 26829121 TI - The Effects of NF-kappaB and c-Jun/AP-1 on the Expression of Prothrombotic and Proinflammatory Molecules Induced by Anti-beta2GPI in Mouse. AB - Our previous data demonstrated that nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) are involved in the process of anti-beta2GPI/beta2GPI induced tissue factor (TF) expression in monocytes. However, the role of NF kappaB and AP-1 in pathogenic mechanisms of antiphospholipid syndrome (APS) in vivo has been rarely studied. This study aimed to investigate whether NF-kappaB and c-Jun/AP-1 are involved in anti-beta2GPI-induced expression of prothrombotic and proinflammatory molecules in mouse. IgG-APS or anti-beta2GPI antibodies were injected into BALB/c mice in the presence or absence of PDTC (a specific inhibitor of NF-kappaB) and Curcumin (a potent inhibitor of AP-1) treatment. Our data showed that both IgG-APS and anti-beta2GPI could induce the activation of NF kappaB and c-Jun/AP-1 in mouse peritoneal macrophages. The anti-beta2GPI-induced TF activity in homogenates of carotid arteries and peritoneal macrophages from mice could significantly decrease after PDTC and/or Curcumin treatment, in which PDTC showed the strongest inhibitory effect, but combination of two inhibitors had no synergistic effect. Furthermore, anti-beta2GPI-induced expression of TF, VCAM-1, ICAM-1 and E-selectin in the aorta and expression of TF, IL-1beta, IL-6 and TNF-alpha in peritoneal macrophages of mice were also significantly attenuated by PDTC and/or Curcumin treatment. These results indicate that both NF kappaB and c-Jun/AP-1 are involved in regulating anti-beta2GPI-induced expression of prothrombotic and proinflammatory molecules in vivo. Inhibition of NF-kappaB and c-Jun/AP-1 pathways may be beneficial for the prevention and treatment of thrombosis and inflammation in patients with APS. PMID- 26829125 TI - Correction: Game Theoretical Analysis on Cooperation Stability and Incentive Effectiveness in Community Networks. PMID- 26829124 TI - Continuous Influx of Genetic Material from Host to Virus Populations. AB - Many genes of large double-stranded DNA viruses have a cellular origin, suggesting that host-to-virus horizontal transfer (HT) of DNA is recurrent. Yet, the frequency of these transfers has never been assessed in viral populations. Here we used ultra-deep DNA sequencing of 21 baculovirus populations extracted from two moth species to show that a large diversity of moth DNA sequences (n = 86) can integrate into viral genomes during the course of a viral infection. The majority of the 86 different moth DNA sequences are transposable elements (TEs, n = 69) belonging to 10 superfamilies of DNA transposons and three superfamilies of retrotransposons. The remaining 17 sequences are moth sequences of unknown nature. In addition to bona fide DNA transposition, we uncover microhomology mediated recombination as a mechanism explaining integration of moth sequences into viral genomes. Many sequences integrated multiple times at multiple positions along the viral genome. We detected a total of 27,504 insertions of moth sequences in the 21 viral populations and we calculate that on average, 4.8% of viruses harbor at least one moth sequence in these populations. Despite this substantial proportion, no insertion of moth DNA was maintained in any viral population after 10 successive infection cycles. Hence, there is a constant turnover of host DNA inserted into viral genomes each time the virus infects a moth. Finally, we found that at least 21 of the moth TEs integrated into viral genomes underwent repeated horizontal transfers between various insect species, including some lepidopterans susceptible to baculoviruses. Our results identify host DNA influx as a potent source of genetic diversity in viral populations. They also support a role for baculoviruses as vectors of DNA HT between insects, and call for an evaluation of possible gene or TE spread when using viruses as biopesticides or gene delivery vectors. PMID- 26829127 TI - Trace Mineral Overload Induced Hepatic Oxidative Damage and Apoptosis in Pigs with Long-Term High-Level Dietary Mineral Exposure. AB - The present study investigated the effects of dietary trace mineral (Cu, Fe, Mn, and Zn) supplemental strategies on liver oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis of pigs. A total of 96 Duroc * Landrace * Yorkshire (DLY) piglets were randomly divided into four groups: considered or not considered the trace mineral concentrations in basal diet, and then added to the requirements proposed by NRC (2012) (+B/NR or -B/NR); and considered or not considered the basal diet's trace mineral concentrations and then added to the level of commercial trace mineral supplement (+B/PL or -B/PL). Pigs were fed from 6.5 to 115 kg. Compared with +B/NR diets, -B/PL diets increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations (P < 0.05), resulted in high levels of Fe, Cu, Mn, and Zn accumulation in liver (P < 0.05), as well as led to hepatic oxidative damage with the high concentrations of thiobarbituric acid reactive substance (TBARS), protein carbonylation (PCO), and 8-hydroxyguanine (8-OHG) in liver (P < 0.05). Furthermore, pigs fed -B/PL diets increased CCAAT/enhancer-binding protein homologous protein (CHOP), eukaryotic initiation factor-2alpha (eIF-2a), interleukin-6(IL-6), B-cell lymphoma leukemia 2-associated X protein (Bax), and caspase-3, caspase-8, and caspase-9 gene expression (P < 0.05) in liver. -B/PL diets also up-regulated hepatic mRNA expression of phosphoenolpyruvate carboxykinase1 (PEPCK1), glucose-6-phosphatase (G6PC), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS) (P < 0.05) and down-regulated hormone-sensitive lipase (HSL) mRNA expression (P < 0.05) when compared with those of the + B/NR diet group. Taken together, the results indicated that long-term dietary mineral exposure with the commercial supplement level could cause harm to the structure and metabolic function of liver in pigs. PMID- 26829126 TI - Analyses of the Binding between Water Soluble C60 Derivatives and Potential Drug Targets through a Molecular Docking Approach. AB - Fullerene C60, a unique sphere-shaped molecule consisting of carbon, has been proved to have inhibitory effects on many diseases. However, the applications of C60 in medicine have been severely hindered by its complete insolubility in water and low solubility in almost all organic solvents. In this study, the water soluble C60 derivatives and the C60 binding protein's structures were collected from the literature. The selected proteins fall into several groups, including acetylcholinesterase, glutamate racemase, inosine monophosphate dehydrogenase, lumazine synthase, human estrogen receptor alpha, dihydrofolate reductase and N myristoyltransferase. The C60 derivatives were docked into the binding sites in the proteins. The binding affinities of the C60 derivatives were calculated. The bindings between proteins and their known inhibitors or native ligands were also characterized in the same way. The results show that C60 derivatives form good interactions with the binding sites of different protein targets. In many cases, the binding affinities of C60 derivatives are better than those of known inhibitors and native ligands. This study demonstrates the interaction patterns of C60 derivatives and their binding partners, which will have good impact on the fullerene-based drug discovery. PMID- 26829129 TI - Frontlines: 'Brain Housing Groups' and BMET Excellence. PMID- 26829128 TI - Low-dose radiotherapy and concurrent FOLFIRI-bevacizumab: a Phase II study. AB - AIMS: Low-dose radiation therapy (LDRT) can increase biological efficacy of chemotherapy. This Phase II trial evaluates LDRT plus FOLFIRI-bevacizumab (FOLFIRI-B) in metastatic colorectal cancer. MATERIALS & METHODS: PRIMARY OBJECTIVE: raising the clinical complete response rate from 5 to 25%. SECONDARY OBJECTIVES: toxicity, progression-free survival. Patients underwent 12 FOLFIRI-B cycles plus two daily LDRT fractions (20 cGy/6 h interval) on each cycle. Statistical analysis was planned on 18 patients. RESULTS: Results on 18 patients are reported. Specifically considering irradiated sites: 15/18 patients had a partial (11/18) or complete (4/18) response. Among 11 partial responders, three became a pathological CR after surgery. Grade 3-4 toxicity was recorded in two patients (11.1%). At median follow-up of 30 months (range: 8-50), 7/18 patients progressed in irradiated sites. CONCLUSION: Seven out of 18 patients (38.9%) had clinical or pathological CR in lesions treated with LDRT. Further studies on this newer treatment modality seem justified. PMID- 26829132 TI - Ten Questions With .... PMID- 26829134 TI - Ask George. PMID- 26829135 TI - BMET Training: What Can the Military Teach Us? PMID- 26829136 TI - Cybersecurity for Medical Device Manufacturers: Ensuring Safety and Functionality. PMID- 26829137 TI - How to Measure Productivity in Sterile Processing. PMID- 26829138 TI - Delivering Team-Focused Technology to the Bedside. PMID- 26829139 TI - Special Series: A Clinical Engineer's Approach to CMS Compliance: Part Three. PMID- 26829140 TI - In Contracts with Device Vendors, Mayo Clinic Emphasizes Security. PMID- 26829142 TI - Blazing New Trails: How Women Are Making Inroads into HTM. PMID- 26829141 TI - A Roundtable Discussion: Enhancing Supportability of Healthcare Technology. PMID- 26829143 TI - Advances in Medical Devices Yield Savings throughout Healthcare, Says Boisier. PMID- 26829144 TI - Improved Automation Helps Group Strengthen End-of-Support Data. PMID- 26829145 TI - When Your Device Loses Track of Time. PMID- 26829147 TI - Pursuing Certification: A Worthwhile Endeavor. PMID- 26829148 TI - Supportability Nirvana. PMID- 26829150 TI - Nanoparticle-blood interactions: the implications on solid tumour targeting. AB - Nanoparticles are suitable platforms for cancer targeting and diagnostic applications. Typically, less than 10% of all systemically administered nanoparticles accumulate in the tumour. Here we explore the interactions of blood components with nanoparticles and describe how these interactions influence solid tumour targeting. In the blood, serum proteins adsorb onto nanoparticles to form a protein corona in a manner dependent on nanoparticle physicochemical properties. These serum proteins can block nanoparticle tumour targeting ligands from binding to tumour cell receptors. Additionally, serum proteins can also encourage nanoparticle uptake by macrophages, which decreases nanoparticle availability in the blood and limits tumour accumulation. The formation of this protein corona will also increase the nanoparticle hydrodynamic size or induce aggregation, which makes nanoparticles too large to enter into the tumour through pores of the leaky vessels, and prevents their deep penetration into tumours for cell targeting. Recent studies have focused on developing new chemical strategies to reduce or eliminate serum protein adsorption, and rescue the targeting potential of nanoparticles to tumour cells. An in-depth and complete understanding of nanoparticle-blood interactions is key to designing nanoparticles with optimal physicochemical properties with high tumour accumulation. The purpose of this review article is to describe how the protein corona alters the targeting of nanoparticles to solid tumours and explains current solutions to solve this problem. PMID- 26829151 TI - Speckle Tracking Echocardiography to Evaluate for Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease. AB - Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD), increasing morbidity and mortality. Current echocardiographic measures have poor predictive value for the diagnosis of PH in COPD. Right ventricular (RV) strain obtained by speckle tracking echocardiography (STE) is a measure of myocardial deformation which correlates with RV function and survival in subjects with pulmonary arterial hypertension. We hypothesized that RV strain measurements would be feasible and correlate with invasive hemodynamic measurements in patients with COPD. Retrospective analysis of RV strain values from subjects with severe COPD with echocardiogram within 48 hours of right heart catheterization was performed. First, 54 subjects were included in the analysis. Right ventricular systolic pressure (RVSP) and RV strain could be estimated in 31% and 57%, respectively. Then, 61% had RV-focused apical views, and of those, RV strain could be obtained for 94%. RV free wall strain correlated with PVR (r = 0.41, p = 0.02). Subjects with pulmonary vascular resistance (PVR) > 3 Wood units (WU) had less negative (worse) RV free wall strain values than those with PVR <= 3 WU, with a median strain of -20 (-23, -12) versus -23 (-29, 15), p < 0.05. A receiver operating characteristic curve demonstrated an RV free wall strain of > -23 to be 92% sensitive and 44% specific for identifying PVR > 3 WU (AUC 0.71). RV strain estimates are feasible in the majority of subjects with severe COPD. RV strain correlates with PVR and may improve screening for PH in subjects with COPD. PMID- 26829152 TI - Community Engagement and Data Disclosure in Environmental Health Research. AB - Federal funding agencies increasingly support stakeholder participation in environmental health studies, and yet there is very little published research on engagement of community members in the development of data disclosure (DD) strategies. The Ohio Environmental Protection Agency reported airborne manganese (Mn) concentrations in East Liverpool, Ohio, 30 times higher than the reference concentration, which led to an academic-community research partnership to address community concern about Mn exposure, particularly among children. Children and their families were recruited to participate in a pilot study. Samples of blood and hair were collected from the children and analyzed for metals. DD mechanisms were developed using an iterative approach between community and academic partners. Individual DD letters were mailed to each participating family, and a community meeting was held. A post-meeting survey was administered to gauge community perception of the DD strategies. The purpose of this article is to demonstrate the effectiveness of engaging community partners in the conduct of environmental health research and in the development of DD strategies for individuals and the community at large. Scientists should include community partners in the development of DD strategies to enhance translation of the research findings and support the right of study participants to know their individual results. PMID- 26829153 TI - Impact of external medium conductivity on cell membrane electropermeabilization by microsecond and nanosecond electric pulses. AB - The impact of external medium conductivity on the efficiency of the reversible permeabilisation caused by pulsed electric fields was investigated. Pulses of 12 ns, 102 ns or 100 MUs were investigated. Whenever permeabilisation could be detected after the delivery of one single pulse, media of lower conductivity induced more efficient reversible permeabilisation and thus independently of the medium composition. Effect of medium conductivity can however be hidden by some saturation effects, for example when pulses are cumulated (use of trains of 8 pulses) or when the detection method is not sensitive enough. This explains the contradicting results that can be found in the literature. The new data are complementary to those of one of our previous study in which an opposite effect of the conductivity was highlighted. It stresses that the conductivity of the medium influences the reversible permeabilization by several ways. Moreover, these results clearly indicate that electropermeabilisation does not linearly depend on the energy delivered to the cells. PMID- 26829154 TI - Frictional Properties of Nanojunctions Including Atomically Thin Sheets. AB - Using nonequilibrium molecular dynamics simulations and a coarse-grained description of a system, we have investigated frictional properties of nanojunctions including atomically thin sheets embedded between metal surfaces. We found that the frictional properties of the junctions are determined by the interplay between the lattice mismatch of the contacting surfaces and out-of plane displacements of the sheet. The simulations provide insight into how and why the frictional characteristics of the nanojunctions are affected by the commensurate-incommensurate transition. We demonstrated that in order to achieve a superlow friction, the graphene sheet should be grown on or transferred to the surface with morphology, which is close to that of the graphene (for instance, Cu), while the second confining surface should be incommensurate with the graphene (e.g., Au). Our results suggest an avenue for controlling nanoscale friction in layered materials and provide insights in the design of heterojunctions for nanomechanical applications. PMID- 26829155 TI - Applicability of linear and nonlinear retention-time models for reversed-phase liquid chromatography separations of small molecules, peptides, and intact proteins. AB - The applicability and predictive properties of the linear solvent strength model and two nonlinear retention-time models, i.e., the quadratic model and the Neue model, were assessed for the separation of small molecules (phenol derivatives), peptides, and intact proteins. Retention-time measurements were conducted in isocratic mode and gradient mode applying different gradient times and elution strength combinations. The quadratic model provided the most accurate retention factor predictions for small molecules (average absolute prediction error of 1.5%) and peptides separations (with a prediction error of 2.3%). An advantage of the Neue model is that it can provide accurate predictions based on only three gradient scouting runs, making tedious isocratic retention-time measurements obsolete. For peptides, the use of gradient scouting runs in combination with the Neue model resulted in better prediction errors (<2.2%) compared to the use of isocratic runs. The applicability of the quadratic model is limited due to a complex combination of error and exponential functions. For protein separations, only a small elution window could be applied, which is due to the strong effect of the content of organic modifier on retention. Hence, the linear retention-time behavior of intact proteins is well described by the linear solvent strength model. Prediction errors using gradient scouting runs were significantly lower (2.2%) than when using isocratic scouting runs (3.2%). PMID- 26829156 TI - Widespread Occurrence of Benzotriazoles and Benzothiazoles in Tap Water: Influencing Factors and Contribution to Human Exposure. AB - Despite the frequent detection of benzotriazoles (BTRs) and benzothiazoles (BTHs) in groundwater and surface-water environments, knowledge on their occurrence and profile in tap water is still scarce. This study demonstrates widespread occurrence of these compounds in tap water from 51 major cities in China, which have ranges of G single nucleotide polymorphism (SNP) at coding nucleotide (c.) 125 in exon 2 defines the FY*01 allele, which encodes the antithetical Fy(a). A C>T SNP at c.265 in the FY*02 allele is associated with weakening of Fy(b) expression on red blood cells (R BCs) (called Fy(x)). until recently, this latter change had not been described on a FY*01 background allele. Phenotype-matched units were desired for a multi transfused Vietnamese fetus with alpha-thalassemia. Genotyping of the fetus using a microarray assay that interrogates three SNPs (c.1-67, c.125, and c.265) in FY yielded indeterminate results for the predicted Duffy phenotype. Genomic sequencing of FY exon 2 showed that the fetal sample had one wild-type FY*01 allele and one new FY*01 allele with the c.265C>T SNP, which until recently had only been found on the FY*02 allele. Genotyping performed on samples from the proband's parents indicated that the father had the same FY genotype as the fetus. Flow cytometry, which has been previously demonstrated as a useful method to study antigen strength on cells, was used to determine if this new FY*01 allele was associated with reduced Fy(a) expression on the father's RBCs. Median fluorescence intensity of the father's RBCs (after incubation with anti-FY(a) and fluorescein-labeled anti-IgG) was similar to known FY*01 heterozygotes. and significantly weaker than known FY*01 homozygotes. In conclusion, the fetus and father both had one normal FY*01 allele and one new FY*01W.01, is associated with weakened expression of Fy(a) on RBCs. PMID- 26829174 TI - A New Self-Consistent Field Model of Polymer/Nanoparticle Mixture. AB - Field-theoretical method is efficient in predicting assembling structures of polymeric systems. However, it's challenging to generalize this method to study the polymer/nanoparticle mixture due to its multi-scale nature. Here, we develop a new field-based model which unifies the nanoparticle description with the polymer field within the self-consistent field theory. Instead of being "ensemble averaged" continuous distribution, the particle density in the final morphology can represent individual particles located at preferred positions. The discreteness of particle density allows our model to properly address the polymer particle interface and the excluded-volume interaction. We use this model to study the simplest system of nanoparticles immersed in the dense homopolymer solution. The flexibility of tuning the interfacial details allows our model to capture the rich phenomena such as bridging aggregation and depletion attraction. Insights are obtained on the enthalpic and/or entropic origin of the structural variation due to the competition between depletion and interfacial interaction. This approach is readily extendable to the study of more complex polymer-based nanocomposites or biology-related systems, such as dendrimer/drug encapsulation and membrane/particle assembly. PMID- 26829176 TI - Clinical and reference lab characteristics of patients with suspected direct antiglobulin test (DAT)-negative immune hemolytic anemia. AB - Clinical evidence of warm autoimmune hemolytic anemia is present in 1 percent to 10 percent of patients whose direct antiglobulin test (DAT) is negative. The clinical underpinnings associated with DAT-negative immune hemolysis are poorly understood, and the current study aimed to further define the clinical characteristics associated with this form of anemia. A 19-question survey, requesting clinical information about each patient, was retrospectively mailed to all referring labs that had sent patient samples for an enhanced DAT evaluation from January 2011 through June 2013. An enhanced DAT evaluation involved a standard DAT and DATs performed using gel, polyethylene glycol, and 4 degrees C low-ionic strength saline wash. We obtained detailed clinical information from 57 patients with an enhanced DAT investigation. Eighteen of these 57 patients (31.6%) were found to have a positive DAT, 11 (19.3%) of which were found to have a positive enhanced DAT (2 were positive by enhanced methods methods and negative by standard methods). The reported mean nadir hemoglobin for all 57 patients was 7.8% g/dL (range 3.2-12.7), and lactate dehydrogenase was 827.8 U/L (range 136 6917). Thirty-seven (18.1%) presented with a haptoglobin <10 mg/dL, and 21 (48.8%) reported spherocytes on peripheral smear. About half of the respondents reported using steroids as treatment for the anemia, and 4 of the 18 DAT-positive respondents (23.5%) changed their treatment plan because of the reference laboratory results. One patient died as a result of the reported hemolytic anemia (2.0%). We conclude that immune hemolysis detected by enhanced DAT methods is relatively common, and enhanced DAT methods are valuable tools in the diagnosis and management of patients with DAT-negative hemolytic anemia. PMID- 26829177 TI - Blocked D phenomenon and relevance of maternal serologic testing. AB - A blood requisition for double-volume exchange transfusion was received for a 2 day-old male child born to a 29-year-old multiparous female (P2002) referred to our institute having neonatal jaundice with encephalopathy; no maternal sample was received. the neonatal blood sample was typed as group A, D-, and the direct antiglobulin test (DAT) was strongly positive (4+) using the gel method. Mono specific DAT showed the presence of IgG antibodies on neonatal red blood cells (RBCs). Acid elution and gentle heat elution (at 56 degrees C) confirmed the presence of anti-D on neonatal RBCs. The baby received two exchange transfusions with group O, D-, packed RBCs compatible with his own serum. Later, on day 3, the neonate's mother was typed as group AB, D-, and her serum revealed the presence of alloanti-D, -C, and -S reactive in the anti-human globulin phase. The anti-D titer was 1024. this report highlights the "blocking" phenomenon caused by maternal anti-D in a case of hemolytic disease of fetus and newborn with a positive DAT. PMID- 26829178 TI - Anti-Jk3 in a Filipino man. AB - A 62-year-old Filipino man with a history of chronic obstructive pulmonary disease, hypertension, and hyperlipidemia was admitted to the emergency department at Hospital A with recurrent fevers, weakness, and jaundice. The patient was evaluated and eventually discharged with a diagnosis of possible drug induced hepatitis. One month later, the patient was admitted to Hospital B for recurrent fevers and weakness. The patient's hemoglobin was 3.8 g/dL. Six units of packed red blood cells (RBCs) were ordered for transfusion. The patient's sample typed as group B, D+, and the antibody screen was negative. All six units of packed RBCs appeared compatible (at immediate spin) and were transfused to the patient. His hemoglobin level 4 days post-transfusion was 9.3 g/dL, and the patient was discharged. The patient returned after a week for follow-up and his hemoglobin was found to have dropped to 8.5 g/dL, which continued to fall until it reached 7.0 g/dL. Additional packed RBCs were ordered for transfusion. during subsequent pre-transfusion compatibility testing, the antibody screen was found to be positive (all screening cells reactive at the antihuman globulin phase). An antibody identification panel was performed.The patient's serum was found to react with all panel cells tested, including the autocontrol tube. A direct antiglobulin test revealed the presence of both anti-IgG and anti-C3 coating the patient's RBCs. The specimen was then sent to a reference laboratory for further testing. Results from the reference lab testing revealed the presence of anti-Jk3 in the patient's serum. the patient was placed on steroids, and his reticulocyte count increased with no further signs of extravascular hemolysis. No additional transfusions were necessary. he was eventually discharged with a hemoglobin of 13.6 g/dL. the purpose of this case study is to report the findings of an extremely rare but clinically significant antibody, anti-Jk3. PMID- 26829179 TI - Case report: Severe hemolytic disease of the fetus and newborn due to anti-C+G. AB - Anti-G is commonly present with anti-D and/or anti-C and can confuse serological investigations. in general, anti-G is not considered a likely cause of severe hemolytic disease of the fetus and newborn (HDFN), but it is important to differentiate it from anti-D in women who should be administered anti-D immunoglobulin prophylaxis. We report one woman with three pregnancies severely affected by anti-C+G requiring intrauterine treatment and a review of the literature. In our case, the identification of the correct antibody was delayed because the differentiation of anti-C+G and anti-D+C was not considered important during pregnancy since the father was D-. In addition, anti-C+G and anti-G titer levels were not found to be reliable as is generally considered in Rh immunization. Severe HDFN occurred at a maternal anti-C+G antibody titer of S and anti-G titer of 1 in comparison with the critical titer level of 16 or more in our laboratory. close collaboration between the immunohematology laboratory and the obstetric unit is essential. In previously affected families, early assessment for fetal anemia is required even when titers are low. PMID- 26829180 TI - CD177/NB1 receptor expression is dynamically regulated in sepsis patients. PMID- 26829181 TI - Alternative to providing ABO-incompatible donors for patients in end-stage renal disease: renal transplant registries, the need of the hour. PMID- 26829182 TI - It's an emergency to them. PMID- 26829183 TI - Adolescent Emotional Pathology and Lifetime History of Alcohol or Drug Use With and Without Comorbid Tobacco Use. AB - OBJECTIVE: Use of drugs and alcohol, including tobacco, is linked to adolescent emotional psychopathology. Given that tobacco use is becoming less common over recent years, its co-use with drugs/alcohol may mark a more severe profile of emotional symptomatology. However, it is unclear whether teens with a lifetime history of using drug/alcohol and tobacco exhibit additional elevations in emotional psychopathology and/or multiple forms of emotional psychopathology compared to teens with lifetime drug/alcohol use without comorbid tobacco use. This cross-sectional study compared emotional disorder symptoms and emotional vulnerability traits among adolescents with varying histories of substance use. METHODS: Ninth-grade students enrolled at two schools in Los Angeles, California, were recruited; 575 met eligibility criteria and provided both student assent and parental consent. Students completed self-report measures of emotional pathology, transdiagnostic, and lifetime substance use. Participants were classified into three groupings: (a) no history of substance use (n = 294); (b) lifetime history of drug/alcohol use without tobacco use (n = 166); and (c) lifetime history of drug/alcohol use with concomitant tobacco use (n = 115). RESULTS: Chi-square results showed that teens with lifetime alcohol/drug use with (vs. without) comorbid tobacco use were more likely to have used 10 of 16 substances assessed in the study. Post-ANOVA pairwise tests revealed that, compared to students with no history of substance use, those with any history of use (alcohol/drugs with and without tobacco use) had higher major depression symptoms and negative affect. Those with lifetime alcohol/drug use with comorbid tobacco use had higher generalized anxiety symptoms and distress, and those with lifetime alcohol/drug use without comorbid tobacco use had higher panic disorder symptoms and anhedonia. There were no significant differences between adolescents with lifetime drug/alcohol use with comorbid tobacco use versus those without tobacco use. CONCLUSIONS: Adolescents with (vs. without) a lifetime history of drug/alcohol use endorse greater emotional symptomatology and trait vulnerabilities, regardless of comorbid lifetime tobacco use. Thus, the extent to which tobacco serves as a gateway to, correlate of, or consequence of other substance use may have little bearing on adolescent emotional health. This study's findings further suggest that emotional vulnerability (in addition to manifest psychopathology) should be considered in adolescent substance use and mental illness prevention. PMID- 26829184 TI - Effect of long chain omega-3 polyunsaturated fatty acids on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial. AB - BACKGROUND: Obesity is a degree of excess weight that predisposes people to metabolic syndromes via an inflammatory mechanism. Hypertensive and diabetic people have higher risks of developing systemic inflammation. Long chain omega-3 polyunsaturated fatty acids (LC omega-3 PUFAs) can reduce the cardiovascular events and help against inflammation. OBJECTIVE: To identify the effects of LC omega-3 PUFAs on reducing the levels of inflammatory markers on hypertensive and/or diabetic obese adults. MATERIALS AND METHODS: Sixty-four patients, who were hypertensive and/or diabetic obese with high levels of inflammatory markers, from primary healthcare centers of Gaza City, Palestine, enrolled in two groups of an open-label, parallel, randomized, controlled trial for 8 weeks. Thirty three patients were in the control group, and 31 patients were in the experimental group. The experimental group was treated with a daily dose of 300 mg eicosapentaenoic acid and 200 mg of docosahexaenoic acid. RESULTS: Treatment with LC omega-3 PUFAs significantly reduced the level of high sensitivity C reactive protein (hs-CRP) [14.78+/-10.7 to 8.49+/-6.69 mg/L, p<0.001], fasting blood glucose (FBG) [178.13+/-58.54 to 157.32+/-59.77 mg/dL, p=0.024], and triglyceride (TG) [209.23+/-108.3 to 167.0+/-79.9 mg/dL, p<0.05] after 8 weeks of treatment, whereas no significant changes appeared in interleukin 6 (IL-6) and total cholesterol (TC). In the control group, significant reduction was detected for FBG [187.15+/-64.8 to 161.91+/-37.9 mg/dL, p<0.05] and TG [202.91+/-107.0 to 183.45+/-95.82 mg/dL, p<0.05], and no changes for hs-CRP, IL-6, or TC. By comparing the experimental group with the changes of control group at the endpoint, LC omega-3 PUFAs did not reach the clinical significance in treating effectiveness for any of the clinical variables. CONCLUSION: LC omega-3 PUFAs have recommended effects on health; the obtained results can improve the role of LC omega-3 PUFAs as a protective factor on inflammation and metabolic dysregulation. The time allowed or the dose used could be insufficient to achieve full treatment affectivity. PMID- 26829185 TI - Effects of maternal mild zinc deficiency and different ways of zinc supplementation for offspring on learning and memory. AB - BACKGROUND: The effect of different ways of zinc supplementation on spatial learning and memory remains unclear. OBJECTIVES: This study aims to assess the effectiveness of two ways of zinc supplementation - oral use and intravenous transfusion - in zinc-deficient offspring rats on learning and memory. DESIGN: Rats were randomly divided into six groups on the first day of pregnancy (n=12): control (CO), pair fed (PF), zinc deprived (ZD), oral zinc supplementation (OZS), injection zinc supplementation (IZS), and injection control. The offspring's spatial learning and memory were tested at postnatal day 35 using Morris water maze (MWM). Maternal rats' serum zinc was measured at postnatal day 21, while pups' serum zinc was measured at postnatal day 35. RESULTS: Compared with the CO and PF groups, pups in ZD group spent more time finding the latent platform and swam longer distances (p<0.05). Compared with ZD groups, pups in OZS group significantly decreased the time used for finding the platform and the swimming distance (p<0.05) and were similar to that of CO and PF groups (p>0.05). However, compared with ZD groups, pups in IZS did not show any improvement in the indexes of MWM (p>0.05) although their zinc serum concentration increased significantly (p<0.05). CONCLUSIONS: These results indicate that mild zinc deficiency during pregnancy and lactation leads to the impairment of learning and memory function in offspring, and that OZS, instead of intravenous transfusion zinc supplementation, can recover the impairment of spatial learning and memory function. PMID- 26829186 TI - Supplementation with a fish protein hydrolysate (Micromesistius poutassou): effects on body weight, body composition, and CCK/GLP-1 secretion. AB - BACKGROUND: Fish protein hydrolysates (FPHs) have been reported as a suitable source of proteins for human nutrition because of their balanced amino acid composition and positive effect on gastrointestinal absorption. OBJECTIVE: Here, we investigated the effect of a FPH, Slimpro((r)), obtained from blue whiting (Micromesistius poutassou) muscle by enzymatic hydrolysis, on body composition and on stimulating cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) secretion. DESIGN: A randomized clinical study was carried out on 120, slightly overweight (25 kg/m(2) <= BMI<30 kg/m(2)), male (25%) and female (75%) subjects. FPH was tested in a food supplement at two doses (1.4 and 2.8 g) to establish if a dose-effect relationship exists. Product use was associated with a mild hypocaloric diet (-300 kcal/day). Body composition (body weight; fat mass; extracellular water; and circumference of waist, thighs, and hips) and CCK/GLP-1 blood levels were measured at the beginning of the study and after 45 and 90 days of product use. CCK/GLP-1 levels were measured since they are involved in controlling food intake. RESULTS: Treated subjects reported an improvement of body weight composition and an increased blood concentration of both CCK and GLP 1. No differences were found between the 1.4 and 2.8 g FPH doses, indicating a plateau effect starting from 1.4 g FPH. CONCLUSIONS: Both 1.4 and 2.8 g of FPH were effective in improving body composition and in increasing CCK and GLP-1 blood levels. PMID- 26829188 TI - State-to-State Inelastic Scattering of O2 with Helium. AB - Molecular oxygen (O2) is extremely important for a wide variety of processes on and outside Earth. Indeed, O2-He collisions are crucial to model O2 abundance in space or to create ultracold O2 molecules. A crossed molecular beam experiment to probe rotational excitation of O2 due to helium collisions at energies of 660 cm 1 is reported. Velocity map imaging was combined with state-selective detection of O2(X3Sigmag-) by (2+1) resonance-enhanced multiphoton ionization. The obtained raw O2+ images were corrected from density to flux and the differential cross sections (DCS) were then extracted for six O2 final states. Exact quantum mechanical calculations were also performed. A very good agreement between experimental and theoretical DCSs was found by using an initial O2 beam population ratio of 80% for the first rotational state and 20% for the first excited state. The agreement demonstrates our ability to model inelastic processes between O2 molecules and rare gas both theoretically and experimentally. PMID- 26829189 TI - Endoscopic reinforcement of the anastomosis followed by targeted endoscopic hemostasis for massive upper gastrointestinal bleeding after Whipple's surgery. PMID- 26829190 TI - Small intestine grasped by over-the-scope-clip during attempt to close an iatrogenic colonic perforation. PMID- 26829187 TI - Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung. AB - Development of a new drug for the treatment of lung disease is a complex and time consuming process involving numerous disciplines of basic and applied sciences. During the 2015 Congress of the International Society for Aerosols in Medicine, a group of experts including aerosol scientists, physiologists, modelers, imagers, and clinicians participated in a workshop aiming at bridging the gap between basic research and clinical efficacy of inhaled drugs. This publication summarizes the current consensus on the topic. It begins with a short description of basic concepts of aerosol transport and a discussion on targeting strategies of inhaled aerosols to the lungs. It is followed by a description of both computational and biological lung models, and the use of imaging techniques to determine aerosol deposition distribution (ADD) in the lung. Finally, the importance of ADD to clinical efficacy is discussed. Several gaps were identified between basic science and clinical efficacy. One gap between scientific research aimed at predicting, controlling, and measuring ADD and the clinical use of inhaled aerosols is the considerable challenge of obtaining, in a single study, accurate information describing the optimal lung regions to be targeted, the effectiveness of targeting determined from ADD, and some measure of the drug's effectiveness. Other identified gaps were the language and methodology barriers that exist among disciplines, along with the significant regulatory hurdles that need to be overcome for novel drugs and/or therapies to reach the marketplace and benefit the patient. Despite these gaps, much progress has been made in recent years to improve clinical efficacy of inhaled drugs. Also, the recent efforts by many funding agencies and industry to support multidisciplinary networks including basic science researchers, R&D scientists, and clinicians will go a long way to further reduce the gap between science and clinical efficacy. PMID- 26829192 TI - Deep enteroscopy diagnosis of obscure overt gastrointestinal bleeding due to intravascular endothelial hyperplasia missed by capsule endoscopy. PMID- 26829191 TI - Endoscopic ultrasound-guided repositioning of a migrated metal hepatogastrostomy stent using foreign body forceps. PMID- 26829193 TI - Endoscopic ultrasound imaging of pancreatic duct ascariasis. PMID- 26829194 TI - Use of a Soehendra stent retriever in dilation of an anastomotic biliary stricture in a post-liver transplant patient. PMID- 26829195 TI - Percutaneous endoscopic gastrostomy assisted by laparoscopy: is it a valid choice? PMID- 26829196 TI - Endoscopic ultrasound-guided transgastric drainage of a complex multiloculated peritoneal fluid collection as rare complication of lupus peritonitis. PMID- 26829197 TI - Endoscopic ultrasound-guided fine needle aspiration of splenic vein thrombosis: a novel approach to the portal venous system. PMID- 26829198 TI - Tulip-bundle technique as rescue hemostatic therapy in a deep Mallory-Weiss tear. PMID- 26829199 TI - Endoscopic ultrasound-guided ERCP in the treatment of a Todani type-III cyst causing acute necrotizing pancreatitis. PMID- 26829200 TI - Endoscopic ultrasound-guided fine needle aspiration of a pericardial mass. PMID- 26829201 TI - Overtube-assisted placement of a capsule endoscope in a patient with a swallowing disorder. PMID- 26829202 TI - Percutaneous laser application using the SpyGlass system in a patient with intrahepatic lithiasis, liver cirrhosis, and surgically altered anatomy. PMID- 26829203 TI - Assays To Detect the Formation of Triphosphates of Unnatural Nucleotides: Application to Escherichia coli Nucleoside Diphosphate Kinase. AB - One frontier in synthetic biology seeks to move artificially expanded genetic information systems (AEGIS) into natural living cells and to arrange the metabolism of those cells to allow them to replicate plasmids built from these unnatural genetic systems. In addition to requiring polymerases that replicate AEGIS oligonucleotides, such cells require metabolic pathways that biosynthesize the triphosphates of AEGIS nucleosides, the substrates for those polymerases. Such pathways generally require nucleoside and nucleotide kinases to phosphorylate AEGIS nucleosides and nucleotides on the path to these triphosphates. Thus, constructing such pathways focuses on engineering natural nucleoside and nucleotide kinases, which often do not accept the unnatural AEGIS biosynthetic intermediates. This, in turn, requires assays that allow the enzyme engineer to follow the kinase reaction, assays that are easily confused by ATPase and other spurious activities that might arise through "site-directed damage" of the natural kinases being engineered. This article introduces three assays that can detect the formation of both natural and unnatural deoxyribonucleoside triphosphates, assessing their value as polymerase substrates at the same time as monitoring the progress of kinase engineering. Here, we focus on two complementary AEGIS nucleoside diphosphates, 6-amino-5-nitro-3-(1'-beta-D-2' deoxyribofuranosyl)-2(1H)-pyridone and 2-amino-8-(1'-beta-D-2' deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one. These assays provide new ways to detect the formation of unnatural deoxyribonucleoside triphosphates in vitro and to confirm their incorporation into DNA. Thus, these assays can be used with other unnatural nucleotides. PMID- 26829204 TI - Metabolic interplay between white, beige, brown adipocytes and the liver. AB - In mammalian evolution, three types of adipocytes have developed, white, brown and beige adipocytes. White adipocytes are the major constituents of white adipose tissue (WAT), the predominant store for energy-dense triglycerides in the body that are released as fatty acids during catabolic conditions. The less abundant brown adipocytes, the defining parenchymal cells of brown adipose tissue (BAT), internalize triglycerides that are stored intracellularly in multilocular lipid droplets. Beige adipocytes (also known as brite or inducible brown adipocytes) are functionally very similar to brown adipocytes and emerge in specific WAT depots in response to various stimuli including sustained cold exposure. The activation of brown and beige adipocytes (together referred to as thermogenic adipocytes) causes both the hydrolysis of stored triglycerides as well as the uptake of lipids and glucose from the circulation. Together, these fuels are combusted for heat production to maintain body temperature in mammals including adult humans. Given that heating by brown and beige adipocytes is a very-well controlled and energy-demanding process which entails pronounced shifts in energy fluxes, it is not surprising that an intensive interplay exists between the various adipocyte types and parenchymal liver cells, and that this influences systemic metabolic fluxes and endocrine networks. In this review we will emphasize the role of hepatic factors that regulate the metabolic activity of white and thermogenic adipocytes. In addition, we will discuss the relevance of lipids and hormones that are secreted by white, brown and beige adipocytes regulating liver metabolism in order to maintain systemic energy metabolism in health and disease. PMID- 26829206 TI - Mimivirus inaugurated in the 21st century the beginning of a reclassification of viruses. AB - Mimivirus and other giant viruses are visible by light microscopy and bona fide microbes that differ from other viruses and from cells that have a ribosome. They can be defined by: giant virion and genome sizes; their complexity, with the presence of DNA and mRNAs and dozens or hundreds of proteins in virions; the presence of translation-associated components; a mobilome including (pro)virophages (and a defence mechanism, named MIMIVIRE, against them) and transpovirons; their monophyly; the presence of the most archaic protein motifs they share with cellular organisms but not other viruses; a broader host range than other viruses. These features show that giant viruses are specific, autonomous, biological entities that warrant the creation of a new branch of microbes. PMID- 26829205 TI - Impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis. AB - BACKGROUND & AIMS: All oral direct acting antivirals (DAAs) effectively treat chronic hepatitis C virus (HCV) infection, but the benefits in advanced liver disease are unclear. We compared outcomes in treated and untreated patients with decompensated cirrhosis. METHODS: Patients with HCV and decompensated cirrhosis or at risk of irreversible disease were treated in an expanded access programme (EAP) in 2014. Treatment, by clinician choice, was with sofosbuvir, ledipasvir or daclatasvir, with or without ribavirin. For functional outcome comparison, untreated patients with HCV and decompensated cirrhosis who were registered on a database 6months before treatment was available were retrospectively studied. Primary endpoint was sustained virological response 12weeks post antiviral treatment (treated cohort) and the secondary endpoint (both cohorts) was adverse outcomes (worsening in MELD score or serious adverse event) within 6months. RESULTS: 467 patients received treatment (409 decompensated cirrhosis). Viral clearance was achieved in 381 patients (81.6%) - 209 from 231 (90.5%) with genotype 1 and 132 from 192 (68.8%) with genotype 3. MELD scores improved in treated patients (mean change -0.85) but worsened in untreated patients (mean+0.75) (p<0.0001). Patients with initial serum albumin <35g/L, aged >65 or with low (<135mmol/L) baseline serum sodium concentrations were least likely to benefit from therapy. CONCLUSIONS: All oral DAAs effectively cured HCV in patients with advanced liver disease. Viral clearance was associated with improvement in liver function within 6months compared to untreated patients. The longer term impact of HCV treatment in patients with decompensated cirrhosis remains to be determined. PMID- 26829207 TI - Enhanced thermoelectric performance in the Rashba semiconductor BiTeI through band gap engineering. AB - Rashba semiconductors are of great interest in spintronics, superconducting electronics and thermoelectrics. Bulk BiTeI is a new Rashba system with a giant spin-split band structure. 2D-like thermoelectric response has been found in BiTeI. However, as optimizing the carrier concentration, the bipolar effect occurs at elevated temperature and deteriorates the thermoelectric performance of BiTeI. In this paper, band gap engineering in Rashba semiconductor BiTeI through Br-substitution successfully reduces the bipolar effect and improves the thermoelectric properties. By utilizing the optical absorption and Burstein-Moss effect analysis, we find that the band gap in Rashba semiconductor BiTeI increases upon bromine substitution, which is consistent with theoretical predictions. Bipolar transport is mitigated due to the larger band gap, as the thermally-activated minority carriers diminish. Consequently, the Seebeck coefficient keeps increasing with a corresponding rise in temperature, and thermoelectric performance can thus be enhanced with a ZT = 0.5 at 570 K for BiTeI0.88Br0.12. PMID- 26829208 TI - Total Synthesis and Biological Evaluation of Natural and Designed Tubulysins. AB - A streamlined total synthesis of N(14)-desacetoxytubulysin H (Tb1) based on a C-H activation strategy and a short total synthesis of pretubulysin D (PTb-D43) are described. Applications of the developed synthetic strategies and technologies to the synthesis of a series of tubulysin analogues (Tb2-Tb41 and PTb-D42) are also reported. Biological evaluation of the synthesized compounds against an array of cancer cells revealed a number of novel analogues (e.g., Tb14), some with exceptional potencies against certain cell lines [e.g., Tb32 with IC50 = 12 pM against MES SA (uterine sarcoma) cell line and 2 pM against HEK 293T (human embryonic kidney) cell line], and a set of valuable structure-activity relationships. The highly potent cytotoxic compounds discovered in this study are highly desirable as payloads for antibody-drug conjugates and other drug delivery systems for personalized targeted cancer chemotherapies. PMID- 26829209 TI - Association Between Three SNPs and Thromboangiitis Obliterans in Xinjiang Uyghur Population. AB - BACKGROUND: Thromboangiitis obliterans (TAO), also called Buerger's disease, is a chronic peripheral vascular occlusive disease. It is an obliterative vasculitis characterized by arterial thrombosis and strongly associated with tobacco exposure. The pathogenesis and etiology of TAO are not well understood, but genetic factors may be important in its development. A case-control study was undertaken to identify genetic factors potentially involved in the pathogenesis of TAO in a Xinjiang Uyghur population of China, where TAO is common. METHODS: We ascertained 177 TAO patients by clinical screening and 86 healthy individuals from the HAPMAP database. The genotypes of single-nucleotide polymorphisms (SNPs) of the participants were identified using the Affymetrix Genome-Wide Human SNP Array 6.0 to perform a genome wide association study (GWAS). The association between the SNPs and incidence of TAO was quantified using race stratification exposure. RESULTS: Through a case-control GWAS study 26 SNPs were significantly associated with incidence of TAO following a Bonferroni correction. However, after genomic control correction for population stratification only three of these SNPS were highly significantly associated with TAO: rs376511 in IL17RC (OR = 24.4, 95% CI:8.68 - 68.62, p < 0.0001), rs7632505 in SEMA5B (OR = 29.47, 95% CI:7.16 - 121.3, p < 0.0001), and rs10178082 (OR = 18.09, 95% CI: 6.56 - 49.92, p < 0.0001) showed a significant risk of TAO in the Uyghur population. CONCLUSIONS: This study shows an association between these 3 SNPs and susceptibility to TAO in the Uyghur population, suggesting that polymorphisms in the IL-17RC and Sema 5B genes may pre-dispose individuals in this population to development of TAO. These findings require replication. PMID- 26829210 TI - Multiparametric flow cytometric analysis of whole blood reveals changes in minor lymphocyte subpopulations of multiple sclerosis patients. AB - OBJECTIVE: The objective of this study is to characterise the functionally relevant minor lymphocyte subpopulations in whole blood of multiple sclerosis (MS) patients and their potential utility as biomarkers for treatment follow up. MATERIAL AND METHODS: Peripheral blood from 40 healthy donors (HD) and 66 MS patients [23 relapsing-remitting (RRMS) without treatment, 27 RRMS undergoing treatment (16 IFN-beta, 11 natalizumab), and 16 progressive forms (eight secondary progressive and eight primary progressive)] was analysed by multiparametric flow cytometry. RESULTS: Untreated MS patients showed a decrease in early effector memory (CD45RA(-)CCR7(-)CD27(+)) CD4(+) and CD8(+) T cells and an increase in Th17 lymphocytes in peripheral blood compared with HD. Regarding the effect of treatment, whereas no differences in relative percentages of cellular subpopulations were observed in patients under IFN-beta treatment, those under treatment with natalizumab had an increased percentage of early effector memory CD4(+) (CD45RA(-)CCR7(-)CD27(+)), central memory CD8(+) (CD45RA( )CCR7(+)CD27(+)) T cells, recent thymic emigrants (CD4(+) CD45RA(+)CCR7(+)CD27(+)CD31(+)PTK7(+)) and transitional B cells (CD19(+)CD27( )CD24(hi)CD38(hi)). CONCLUSIONS: Multiparametric flow cytometry analysis of whole blood is a robust, reproducible, and sensitive technology to monitor the effect of MS treatments even in minor lymphocyte subpopulations that might represent useful biomarkers of treatment response. PMID- 26829211 TI - Position on reproductive donors and smallpox vaccine: a committee opinion. AB - Although there is presently no definitive evidence linking vaccinia virus transmission through reproductive cells, the Society for Assisted Reproductive Technology (SART) and the American Society for Reproductive Medicine (ASRM) accordingly recommend that assisted reproductive technology (ART) practitioners consider deferring individuals who are planning on donating gametes for reproductive use (reproductive donors) who have recently received smallpox vaccine or contracted symptomatic vaccinia virus infection through close contact with a vaccine recipient (until after the vaccine or infectious scab has spontaneously separated). Good donor practice further suggests that reproductive donors who are not in good health, including those with recent complications from smallpox vaccine, should be similarly deferred. This document replaces the previous document of the same name last published in 2012 (Fertil Steril 2012;98:e1-e2). PMID- 26829212 TI - RIG-I inhibits the MAPK-dependent proliferation of BRAF mutant melanoma cells via MKP-1. AB - BACKGROUND: BRAF-mutant melanoma is characterized by aggressive metastatic potential and therapeutic resistance. The innate immune receptor RIG-I has emerged as a potential target in melanoma therapies but the contributing pathways involved in anti-cancer activity are poorly characterized. METHODS: Baseline and ATRA-induced expression of RIG-I in nine (3 wild type and 6 BRAF-mutant) melanoma cell lines was measured with Q-PCR and Western blot. Ligand-specific stimulation of RIG-I was detected by Q-PCR and ELISA. Activation of the RIG-I-coupled IRF3, NF-kappaB and MAPK pathways was tested with protein array and Western blot. Cell proliferation and apoptosis was monitored by flow cytometry and cell counting. Down modulation of MKP-1 expression in melanoma cells was performed by specific siRNA. RESULTS: Short-term ATRA pre-treatment increases the expression of RIG-I in BRAF-mutant melanoma cells. Specific activation of RIG-I by 5'ppp-dsRNA leads to increased activity of the IRF3-IFNbeta pathway but does not influence NF kappaB signaling. RIG-I mediates the targeted dephosphorylation of several MAPKs (p38, RSK1, GSK-3alpha/beta, HSP27) via the endogenous regulator MKP-1 resulting in decreased melanoma cell proliferation. CONCLUSION: RIG-I has the potential to exert anticancer activity in BRAF-mutant melanoma via controlling IFNbeta production and MAPK signaling. This is the first study showing that RIG-I activation results in MKP-1-mediated inhibition of cell proliferation via controlling the p38-HSP27, c-Jun and rpS6 pathways thus identifying RIG-I and MKP 1 as novel and promising therapeutical targets. PMID- 26829213 TI - Notch2 signaling promotes osteoclast resorption via activation of PYK2. AB - Notch signaling plays a central role in various cell fate decisions, including skeletal development. Recently, Notch signaling was implicated in osteoclast differentiation and maturation, including the resorption activity of osteoclasts. However, the specific involvement of notch signaling in resorption activity was not fully investigated. Here, we investigated the roles of Notch signaling in the resorption activity of osteoclasts by use of the gamma-secretase inhibitor dibenzazepine (DBZ). Attenuating Notch signaling by DBZ suppressed the expression of NFATc1, a master transcription factor for osteoclast differentiation. However, overexpression of a constitutively active form of NFATc1 did not fully rescue the effects of DBZ. DBZ suppressed the autophosphorylation of PYK2, which is essential for the formation of the podosome belt and sealing zone, with reduced c Src/PYK2 interaction. We found that RANKL increases PYK2 activation accompanied by increased NICD2 production in osteoclasts. Overexpression of NICD2 in osteoclasts rescued DBZ-mediated suppression of resorption activity with promotion of PYK2 autophosphorylation and microtubule acetylation. Consistent with the in vitro results, DBZ strongly suppressed bone destruction in an interleukin-1-induced bone loss model. Collectively, these results demonstrate that Notch2 in osteoclasts plays a role in the control of resorption activity via the PYK2-c-Src-microtubule signaling pathway. PMID- 26829215 TI - Regulator of G protein signaling 8 inhibits protease-activated receptor 1/Gi/o signaling by forming a distinct G protein-dependent complex in live cells. AB - Activation of seven-transmembrane-domain-possessing G protein-coupled receptors (GPCRs) by extracellular stimuli elicits intracellular responses. One class of GPCRs-protease-activated receptors (PARs)-is activated by endogenous proteases, such as thrombin and trypsin. Members of the regulator of G protein signaling (RGS) family stimulate GTP hydrolysis of G protein alpha (Galpha) subunits, thereby inhibiting GPCR/Galpha-mediated signaling. We previously reported that RGS2 and RGS4 inhibit PAR1/Galpha-mediated signaling by interacting with PAR1 in a Galpha-dependent manner. Here, employing the bioluminescence resonance energy transfer (BRET) technique, we identified RGS8 as a novel PAR1-interacting protein. Very little BRET activity was observed between PAR1-Venus (PAR1-Ven) and RGS8-Luciferase (RGS8-Luc) in the absence of Galpha. However, in the presence of Galphao, BRET activity was specifically and significantly increased. This interaction was confirmed by biochemical and immunofluorescence assays. Notably, RGS8 inhibited PAR1/Galphai/o-mediated adenylyl cyclase and ERK activation, and prevented Galphao-induced neurite outgrowth and activation of Necdin protein, a downstream target of Galphao. Our findings suggest a novel function of RGS8 and reveal cellular mechanisms by which RGS8 mediates PAR1 inhibition. PMID- 26829216 TI - Polymerase specific error rates and profiles identified by single molecule sequencing. AB - DNA polymerases have an innate error rate which is polymerase and DNA context specific. Historically the mutational rate and profiles have been measured using a variety of methods, each with their own technical limitations. Here we used the unique properties of single molecule sequencing to evaluate the mutational rate and profiles of six DNA polymerases at the sequence level. In addition to accurately determining mutations in double strands, single molecule sequencing also captures direction specific transversions and transitions through the analysis of heteroduplexes. Not only did the error rates vary, but also the direction specific transitions differed among polymerases. PMID- 26829214 TI - The importance of non-nuclear AR signaling in prostate cancer progression and therapeutic resistance. AB - The androgen receptor (AR) remains the major oncogenic driver of prostate cancer, as evidenced by the efficacy of androgen deprivation therapy (ADT) in naive patients, and the continued effectiveness of second generation ADTs in castration resistant disease. However, current ADTs are limited to interfering with AR ligand binding, either through suppression of androgen production or the use of competitive antagonists. Recent studies demonstrate 1) the expression of constitutively active AR splice variants that no longer depend on androgen, and 2) the ability of AR to signal in the cytoplasm independently of its transcriptional activity (non-genomic); thus highlighting the need to consider other ways to target AR. Herein, we review canonical AR signaling, but focus on AR non-genomic signaling, some of its downstream targets and how these effectors contribute to prostate cancer cell behavior. The goals of this review are to 1) re-highlight the continued importance of AR in prostate cancer as the primary driver, 2) discuss the limitations in continuing to use ligand binding as the sole targeting mechanism, 3) discuss the implications of AR non-genomic signaling in cancer progression and therapeutic resistance, and 4) address the need to consider non-genomic AR signaling mechanisms and pathways as a viable targeting strategy in combination with current therapies. PMID- 26829218 TI - Accuracy of Hysteroscopic Metroplasty With the Combination of Presurgical 3 Dimensional Ultrasonography and a Novel Graduated Intrauterine Palpator: A Randomized Controlled Trial. AB - STUDY OBJECTIVE: To assess whether the use of a novel graduated intrauterine palpator can improve the accuracy of hysteroscopic metroplasty, introducing objective intraoperative criteria. DESIGN: A prospective randomized study (Canadian Task Force I, evidence obtained from a properly design, randomized, controlled trial). SETTING: University Federico II hysteroscopic clinic. PATIENTS: Ninety women with a uterine septum diagnosed during office hysteroscopy and 3-dimesional transvaginal ultrasound (3D-TVS) were randomized into 2 groups: group T (metroplasty with intrauterine palpator) (n = 45) and group C (metroplasty without intrauterine palpator) (n = 45). INTERVENTIONS: Outpatient hysteroscopic metroplasty under conscious sedation using a 5-mm hysteroscope and miniaturized 5F instruments including a bipolar electrode for the removal of three quarters of the septum, blunt scissors to refine the base of the septum, and an intrauterine palpator to measure the portion of the removed septum (only group T). 3D-TVS and second-look hysteroscopy were used to identify the number of optimal (residual septum <5 mm), suboptimal (residual septum 5-10 mm), and incomplete resections (residual septum >10 mm). In group T, metroplasty was stopped when the intrauterine palpator showed that the resected septum corresponded to presurgical ultrasonographic measurements in order to obtain a fundal notch of 1.0 cm. In group C, metroplasty was interrupted once the tubal ostia were clearly visible on the same line and/or hemorrhage from small myometrial vessels of the fundus was observed. MEASUREMENTS AND MAIN RESULTS: No differences were observed in baseline characteristics between the 2 groups. The proportion of patients with complete septum resection was significantly higher in group T (71.5% vs 41%, chi(2): p = .006; relative risk: 1.684; 95% confidence interval, 1.116-2.506). Suboptimal resection was achieved in 13 cases (28.5%) in group T and 14 cases (20%) in group C, whereas incomplete resection was observed in only 12 patients in group C (27%). CONCLUSION: Presurgical evaluation with 3D TVS together with the use of a graduate intrauterine palpator improves the accuracy of hysteroscopic metroplasty, allowing complete removal of a uterine septum in 1 surgical step. PMID- 26829217 TI - CPEB and miR-15/16 Co-Regulate Translation of Cyclin E1 mRNA during Xenopus Oocyte Maturation. AB - Cell cycle transitions spanning meiotic maturation of the Xenopus oocyte and early embryogenesis are tightly regulated at the level of stored inactive maternal mRNA. We investigated here the translational control of cyclin E1, required for metaphase II arrest of the unfertilised egg and the initiation of S phase in the early embryo. We show that the cyclin E1 mRNA is regulated by both cytoplasmic polyadenylation elements (CPEs) and two miR-15/16 target sites within its 3'UTR. Moreover, we provide evidence that maternal miR-15/16 microRNAs co immunoprecipitate with CPE-binding protein (CPEB), and that CPEB interacts with the RISC component Ago2. Experiments using competitor RNA and mutated cyclin E1 3'UTRs suggest cooperation of the regulatory elements to sustain repression of the cyclin E1 mRNA during early stages of maturation when CPEB becomes limiting and cytoplasmic polyadenylation of repressed mRNAs begins. Importantly, injection of anti-miR-15/16 LNA results in the early polyadenylation of endogenous cyclin E1 mRNA during meiotic maturation, and an acceleration of GVBD, altogether strongly suggesting that the proximal CPEB and miRNP complexes act to mutually stabilise each other. We conclude that miR-15/16 and CPEB co-regulate cyclin E1 mRNA. This is the first demonstration of the co-operation of these two pathways. PMID- 26829220 TI - The MCM Helicase Motor of the Eukaryotic Replisome. AB - The MCM motor of the CMG helicase powers ahead of the eukaryotic replication machinery to unwind DNA, in a process that requires ATP hydrolysis. The reconstitution of DNA replication in vitro has established the succession of events that lead to replication origin activation by the MCM and recent studies have started to elucidate the structural basis of duplex DNA unwinding. Despite the exciting progress, how the MCM translocates on DNA remains a matter of debate. PMID- 26829219 TI - Dlx5 Homeodomain:DNA Complex: Structure, Binding and Effect of Mutations Related to Split Hand and Foot Malformation Syndrome. AB - The Dlx5 homeodomain is a transcription factor related to the Drosophila distal less gene that is associated with breast and lung cancer, lymphoma, Rett syndrome and osteoporosis in humans. Mutations in the DLX5 gene have been linked to deficiencies in craniofacial and limb development in higher eukaryotes, including split hand and foot malformation 1 in humans. Our characterization of a Dlx5 homeodomain:(CGACTAATTAGTCG)2 complex by NMR spectroscopy paved the way for determination of its crystal structure at 1.85A resolution that enabled rationalization of the effects of disease-related mutations on the protein function. A Q186H mutation linked to split hand and foot malformation 1 likely affects affinity of DNA binding by disrupting water-mediated interactions with the DNA major groove. A more subtle effect is implicated for the Q178P mutation, which is not in direct contact with the DNA. Our data indicate that these mutations diminish the ability of the Dlx5 homeodomain to recognize and bind target DNAs, and they likely destabilize the formation of functional complexes. PMID- 26829222 TI - Distribution and microbial community structure analysis of a single-stage partial nitritation/anammox granular sludge bioreactor operating at low temperature. AB - In the last decade, autotrophic nitrogen removal technologies based on anammox metabolism have become state of the art in urban and industrial wastewater treatment systems, due to their advantages over traditional nitrogen removal processes. However, their application is currently limited to the treatment of warm wastewater (25-40 degrees C) mainly due to the low growth rate of the anammox bacteria. The extension of the application field to wastewater characterized by lower temperatures (8-20 degrees C), such as those typical for municipal sewage, allows the design of treatment systems with a net energy production. In this study, the distribution and bacterial community structure of a lab-scale single-stage partial nitritation/anammox (PN/A) granular sludge bioreactor operating at low temperatures was analysed using next-generation sequencing techniques. The presence of ammonium-oxidizing bacteria and anammox bacteria was found, but the appearance of other bacterial species shows a complex microbial ecosystem. Evaluation of ecological roles of representative species inside the single-stage PN/A bioreactor was accomplished. Results obtained will be helpful for the future design and operation of PN/A systems performing at low temperatures. PMID- 26829221 TI - Metronomic Doses of Temozolomide Enhance the Efficacy of Carbon Nanotube CpG Immunotherapy in an Invasive Glioma Model. AB - Even when treated with aggressive current therapies, most patients with glioblastoma survive less than two years. Rapid tumor growth, an invasive nature, and the blood-brain barrier, which limits the penetration of large molecules into the brain, all contribute to the poor tumor response associated with conventional therapies. Immunotherapy has emerged as a therapeutic approach that may overcome these challenges. We recently reported that single-walled carbon nanotubes (SWCNTs) can be used to dramatically increase the immunotherapeutic efficacy of CpG oligonucleotides in a mouse model of glioma. Following implantation in the mouse brain, the tumor cell line used in these previous studies (GL261) tends to form a spherical tumor with limited invasion into healthy brain. In order to evaluate SWCNT/CpG therapy under more clinically-relevant conditions, here we report the treatment of a more invasive mouse glioma model (K-Luc) that better recapitulates human disease. In addition, a CpG sequence previously tested in humans was used to formulate the SWCNT/CpG which was combined with temozolomide, the standard of care chemotherapy for glioblastoma patients. We found that, following two intracranial administrations, SWCNT/CpG is well-tolerated and improves the survival of mice bearing invasive gliomas. Interestingly, the efficacy of SWCNT/CpG was enhanced when combined with temozolomide. This enhanced anti-tumor efficacy was correlated to an increase of tumor-specific cytotoxic activity in splenocytes. These results reinforce the emerging understanding that immunotherapy can be enhanced by combining it with chemotherapy and support the continued development of SWCNT/CpG. PMID- 26829223 TI - Multistage coupling of independent laser-plasma accelerators. AB - Laser-plasma accelerators (LPAs) are capable of accelerating charged particles to very high energies in very compact structures. In theory, therefore, they offer advantages over conventional, large-scale particle accelerators. However, the energy gain in a single-stage LPA can be limited by laser diffraction, dephasing, electron-beam loading and laser-energy depletion. The problem of laser diffraction can be addressed by using laser-pulse guiding and preformed plasma waveguides to maintain the required laser intensity over distances of many Rayleigh lengths; dephasing can be mitigated by longitudinal tailoring of the plasma density; and beam loading can be controlled by proper shaping of the electron beam. To increase the beam energy further, it is necessary to tackle the problem of the depletion of laser energy, by sequencing the accelerator into stages, each powered by a separate laser pulse. Here, we present results from an experiment that demonstrates such staging. Two LPA stages were coupled over a short distance (as is needed to preserve the average acceleration gradient) by a plasma mirror. Stable electron beams from a first LPA were focused to a twenty micrometre radius--by a discharge capillary-based active plasma lens--into a second LPA, such that the beams interacted with the wakefield excited by a separate laser. Staged acceleration by the wakefield of the second stage is detected via an energy gain of 100 megaelectronvolts for a subset of the electron beam. Changing the arrival time of the electron beam with respect to the second stage laser pulse allowed us to reconstruct the temporal wakefield structure and to determine the plasma density. Our results indicate that the fundamental limitation to energy gain presented by laser depletion can be overcome by using staged acceleration, suggesting a way of reaching the electron energies required for collider applications. PMID- 26829224 TI - Observing the Rosensweig instability of a quantum ferrofluid. AB - Ferrofluids exhibit unusual hydrodynamic effects owing to the magnetic nature of their constituents. As magnetization increases, a classical ferrofluid undergoes a Rosensweig instability and creates self-organized, ordered surface structures or droplet crystals. Quantum ferrofluids such as Bose-Einstein condensates with strong dipolar interactions also display superfluidity. The field of dipolar quantum gases is motivated by the search for new phases of matter that break continuous symmetries. The simultaneous breaking of continuous symmetries such as the phase invariance in a superfluid state and the translational symmetry in a crystal provides the basis for these new states of matter. However, interaction induced crystallization in a superfluid has not yet been observed. Here we use in situ imaging to directly observe the spontaneous transition from an unstructured superfluid to an ordered arrangement of droplets in an atomic dysprosium Bose Einstein condensate. By using a Feshbach resonance to control the interparticle interactions, we induce a finite-wavelength instability and observe discrete droplets in a triangular structure, the number of which grows as the number of atoms increases. We find that these structured states are surprisingly long-lived and observe hysteretic behaviour, which is typical for a crystallization process and in close analogy to the Rosensweig instability. Our system exhibits both superfluidity and, as we show here, spontaneous translational symmetry breaking. Although our observations do not probe superfluidity in the structured states, if the droplets establish a common phase via weak links, then our system is a very good candidate for a supersolid ground state. PMID- 26829226 TI - Authors' Reply to the Letter by Madias Entitled 'Stroke or Seizures, and Takotsubo Syndrome: A Possibly Underdiagnosed Association'. PMID- 26829225 TI - Cryo-EM structure of the yeast U4/U6.U5 tri-snRNP at 3.7 A resolution. AB - U4/U6.U5 tri-snRNP represents a substantial part of the spliceosome before activation. A cryo-electron microscopy structure of Saccharomyces cerevisiae U4/U6.U5 tri-snRNP at 3.7 A resolution led to an essentially complete atomic model comprising 30 proteins plus U4/U6 and U5 small nuclear RNAs (snRNAs). The structure reveals striking interweaving interactions of the protein and RNA components, including extended polypeptides penetrating into subunit interfaces. The invariant ACAGAGA sequence of U6 snRNA, which base-pairs with the 5'-splice site during catalytic activation, forms a hairpin stabilized by Dib1 and Prp8 while the adjacent nucleotides interact with the exon binding loop 1 of U5 snRNA. Snu114 harbours GTP, but its putative catalytic histidine is held away from the gamma-phosphate by hydrogen bonding to a tyrosine in the amino-terminal domain of Prp8. Mutation of this histidine to alanine has no detectable effect on yeast growth. The structure provides important new insights into the spliceosome activation process leading to the formation of the catalytic centre. PMID- 26829227 TI - Methylation Markers for the Identification of Body Fluids and Tissues from Forensic Trace Evidence. AB - The identification of body fluids is an essential tool for clarifying the course of events at a criminal site. The analytical problem is the fact that the biological material has been very often exposed to detrimental exogenous influences. Thereby, the molecular substrates used for the identification of the traces may become degraded. So far, most protocols utilize cell specific proteins or RNAs. Instead of measuring these more sensitive compounds this paper describes the application of the differential DNA-methylation. As a result of two genome wide screenings with the Illumina HumanMethylation BeadChips 27 and 450k we identified 150 candidate loci revealing differential methylation with regard to the body fluids venous blood, menstrual blood, vaginal fluid, saliva and sperm. Among them we selected 9 loci as the most promising markers. For the final determination of the methylation degree we applied the SNuPE-method. Because the degree of methylation might be modified by various endogenous and exogenous factors, we tested each marker with approximately 100 samples of each target fluid in a validation study. The stability of the detection procedure is proved in various simulated forensic surroundings according to standardized conditions. We studied the potential influence of 12 relatively common tumors on the methylation of the 9 markers. For this purpose the target fluids of 34 patients have been analysed. Only the cervix carcinoma might have an remarkable effect because impairing the signal of both vaginal markers. Using the Illumina MiSeq device we tested the potential influence of cis acting sequence variants on the methylation degree of the 9 markers in the specific body fluid DNA of 50 individuals. For 4 marker loci we observed such an influence either by sole SNPs or haplotypes. The identification of each target fluid is possible in arbitrary mixtures with the remaining four body fluids. The sensitivity of the individual body fluid tests is in the same range as for the forensic STR-analysis. It is the first forensic body fluid protocol which considers the exogenic and endogenic parameters potentially interfering with the true results. PMID- 26829229 TI - Neuromuscular Effects of Common Krait (Bungarus caeruleus) Envenoming in Sri Lanka. AB - OBJECTIVE: We aimed to investigate neurophysiological and clinical effects of common krait envenoming, including the time course and treatment response. METHODOLOGY: Patients with definite common krait (Bungarus caeruleus) bites were recruited from a Sri Lankan hospital. All patients had serial neurological examinations and stimulated concentric needle single-fibre electromyography (sfEMG) of orbicularis oculi in hospital at 6 wk and 6-9 mth post-bite. PRINCIPAL FINDINGS: There were 33 patients enrolled (median age 35 y; 24 males). Eight did not develop neurotoxicity and had normal sfEMG. Eight had mild neurotoxicity with ptosis, normal sfEMG; six received antivenom and all recovered within 20-32 h. Seventeen patients developed severe neurotoxicity with rapidly descending paralysis, from ptosis to complete ophthalmoplegia, facial, bulbar and neck weakness. All 17 received Indian polyvalent antivenom a median 3.5 h post-bite (2.8-7.2 h), which cleared unbound venom from blood. Despite this, the paralysis worsened requiring intubation and ventilation within 7 h post-bite. sfEMG showed markedly increased jitter and neuromuscular blocks within 12 h. sfEMG abnormalities gradually improved over 24 h, corresponding with clinical recovery. Muscle recovery occurred in ascending order. Myotoxicity was not evident, clinically or biochemically, in any of the patients. Patients were extubated a median 96 h post-bite (54-216 h). On discharge, median 8 days (4-12 days) post bite, patients were clinically normal but had mild sfEMG abnormalities which persisted at 6 wk post-bite. There were no clinical or neurophysiological abnormalities at 6-9 mth. CONCLUSIONS: Common krait envenoming causes rapid onset severe neuromuscular paralysis which takes days to recover clinically consistent with sfEMG. Subclinical neuromuscular dysfunction lasts weeks but was not permanent. Antivenom effectively cleared venom but did not prevent worsening or reverse neuromuscular paralysis. PMID- 26829230 TI - Eventual role of EGFR-tyrosine kinase inhibitors in early-stage non-small-cell lung cancer. AB - Nonadvanced non-small-cell lung cancer (NSCLC) has a poor long-term survival from surgery or definitive radiation that is minimally improved with induction/adjuvant conventional chemotherapy. EGFR-tyrosine kinase inhibitors (TKIs), which provide a significant benefit for molecularly selected EGFR-mutant patients with advanced NSCLC, have been infrequently explored in nonadvanced NSCLC to date. Current published studies reported no significant benefit from adding EGFR-TKI to the induction/adjuvant setting. However, many of them present eventual biases such as unpowered statistics, lack of molecular selection, recruitment of low-risk NSCLC, low sample size or unsuitable control arms. Results, strengths and deficiencies of completed and ongoing trials were fully discussed. Similarly, the selection of patients and control arms, the duration and risks of EGFR-TKI therapies in early-stage NSCLC, the evaluation of response and the diagnosis of EGFR status were considered and analyzed. PMID- 26829228 TI - The Genetic Architecture of Murine Glutathione Transferases. AB - Glutathione S-transferase (GST) genes play a protective role against oxidative stress and may influence disease risk and drug pharmacokinetics. In this study, massive multiscalar trait profiling across a large population of mice derived from a cross between C57BL/6J (B6) and DBA2/J (D2)--the BXD family--was combined with linkage and bioinformatic analyses to characterize mechanisms controlling GST expression and to identify downstream consequences of this variation. Similar to humans, mice show a wide range in expression of GST family members. Variation in the expression of Gsta4, Gstt2, Gstz1, Gsto1, and Mgst3 is modulated by local expression QTLs (eQTLs) in several tissues. Higher expression of Gsto1 in brain and liver of BXD strains is strongly associated (P < 0.01) with inheritance of the B6 parental allele whereas higher expression of Gsta4 and Mgst3 in brain and liver, and Gstt2 and Gstz1 in brain is strongly associated with inheritance of the D2 parental allele. Allele-specific assays confirmed that expression of Gsto1, Gsta4, and Mgst3 are modulated by sequence variants within or near each gene locus. We exploited this endogenous variation to identify coexpression networks and downstream targets in mouse and human. Through a combined systems genetics approach, we provide new insight into the biological role of naturally occurring variants in GST genes. PMID- 26829231 TI - Correction: A New Taxon of Basal Ceratopsian from China and the Early Evolution of Ceratopsia. PMID- 26829232 TI - Antiretroviral adherence and treatment outcomes among adult Ethiopian patients. AB - Developing appropriate strategies to sustain optimal medication adherence among the increasing number of HIV-positive patients taking antiretroviral therapy (ART) in sub-Saharan Africa is a major challenge. The objective of this study was to determine patient, regimen, disease, patient-provider, and healthcare-related factors associated with adherence with ART over a one-year period, and assess the impact of adherence on treatment outcomes. We performed a prospective, observational study among 246 patients who were initiated on ART in Ethiopia. Of 172 who completed follow-up, 130 (75.6%) had >=95% adherence. In the multivariate analyses, a higher baseline BMI (OR, 1.2; 95% CI 1.0, 1.4) and use of reminder devices (OR, 9.1; 95% CI 2.0, 41.6) remained positively associated with adherence, while a higher HIV symptom and adverse drug reaction distress score was an independent negative predictor of adherence (OR, 0.90; 95% CI 0.9, 1.0) CD4 count increase was significantly higher in the adherent patients compared to non-adherent patients at 12 months (159 cells/uL [interquartile range (IQR), 72 324 cells/uL] vs. 132 cells/uL [IQR, 43-190 cells/uL]; p = 0.026). Our findings indicate that interventions aimed at improving adherence and thereby treatment outcomes in patients initiated on ART should promote the use of reminder devices, and monitor HIV symptoms and adverse reaction distress and nutritional status. PMID- 26829233 TI - Development of Real-Time PCR Methods for the Detection of Bacterial Meningitis Pathogens without DNA Extraction. AB - Neisseria meningitidis (Nm), Haemophilus influenzae (Hi), and Streptococcus pneumoniae (Sp) are the lead causes of bacterial meningitis. Detection of these pathogens from clinical specimens using traditional real-time PCR (rt-PCR) requires DNA extraction to remove the PCR inhibitors prior to testing, which is time consuming and labor intensive. In this study, five species-specific (Nm-sodC and -ctrA, Hi-hpd#1 and -hpd#3 and Sp-lytA) and six serogroup-specific rt-PCR tests (A, B, C, W, X, Y) targeting Nm capsular genes were evaluated in the two direct rt-PCR methods using PerfeCTa and 5x Omni that do not require DNA extraction. The sensitivity and specify of the two direct rt-PCR methods were compared to TaqMan traditional rt-PCR, the current standard rt-PCR method for the detection of meningitis pathogens. The LLD for all 11 rt-PCR tests ranged from 6,227 to 272,229 CFU/ml for TaqMan, 1,824-135,982 for 5x Omni, and 168-6,836 CFU/ml for PerfeCTa. The diagnostic sensitivity using TaqMan ranged from 89.2% 99.6%, except for NmB-csb, which was 69.7%. For 5x Omni, the sensitivity varied from 67.1% to 99.8%, with three tests below 90%. The sensitivity of these tests using PerfeCTa varied from 89.4% to 99.8%. The specificity ranges of the 11 tests were 98.0-99.9%, 97.5-99.9%, and 92.9-99.9% for TaqMan, 5x Omni, and PerfeCTa, respectively. PerfeCTa direct rt-PCR demonstrated similar or better sensitivity compared to 5x Omni direct rt-PCR or TaqMan traditional rt-PCR. Since the direct rt-PCR method does not require DNA extraction, it reduces the time and cost for processing CSF specimens, increases testing throughput, decreases the risk of cross-contamination, and conserves precious CSF. The direct rt-PCR method will be beneficial to laboratories with high testing volume. PMID- 26829234 TI - Sympathetic Activation is Associated with Exercise Limitation in COPD. AB - Exercise intolerance, skeletal muscle dysfunction, and reduced daily activity are central in COPD patients and closely related to quality of life and prognosis. Studies assessing muscle exercise have revealed an increase in sympathetic outflow as a link to muscle hypoperfusion and exercise limitation. Our primary hypothesis was that muscle sympathetic nerve activity (MSNA) correlates with exercise limitation in COPD. MSNA was evaluated at rest and during dynamic or static handgrip exercise. Additionally, we assessed heart rate, blood pressure, CO2 tension, oxygen saturation (SpO2), and breathing frequency. Ergospirometry was performed to evaluate exercise capacity. We assessed MSNA of 14 COPD patients and 8 controls. In patients, MSNA was negatively correlated with peak oxygen uptake (VO2% pred) (r = -0.597; p = 0.040). During dynamic or static handgrip exercise, patients exhibited a significant increase in MSNA, which was not observed in the control group. The increase in MSNA during dynamic handgrip was highly negatively correlated with peak exercise capacity in Watts (w) and peak oxygen uptake (VO2/kg) (r = -0.853; p = 0.002 and r = -0.881; p = 0.002, respectively). Our study reveals an association between increased MSNA and limited exercise capacity in patients with COPD. Furthermore, we found an increased sympathetic response to moderate physical exercise (handgrip), which may contribute to exercise intolerance in COPD. PMID- 26829235 TI - Comment on "Exposure to Road Traffic Noise and Behavioral Problems in 7-Year-Old Children: A Cohort Study". PMID- 26829237 TI - Formation of free and protein-bound carboxymethyllysine and carboxyethyllysine in meats during commercial sterilization. AB - The effect of commercial sterilization treatments on the levels of advanced glycation endproducts (AGEs) in meats was investigated. The amounts of both free and protein-bound N(epsilon)-carboxymethyllysine (CML) and N(epsilon) carboxyethyllysine (CEL) in beef (rump, ribeye, short plate), pork (hind leg, tenderloin, belly), and chicken (chicken breasts, drumsticks) were determined using an HPLC-MS/MS method. Beef and pork had a small proportion (raw <15%; sterilized <8%) of free AGEs compared to the total AGEs, but raw chicken breasts had very high levels of free CEL (7.12+/-9.98 mg/kg; n=13) with large biological variation compared to pork (0.19+/-0.09 mg/kg; n=9) and beef (0.44+/-0.19 mg/kg; n=9). Commercial sterilization (121 degrees C for 10 min) did not significantly affect the amounts of free CML or CEL, but led to about 0.6- to 3.6-fold increase of protein-bound CML and CEL. The amounts of protein and fat content in beef or pork had very little effect on the formation of protein-bound AGEs during sterilization process. PMID- 26829238 TI - Blended Linear Models for Reduced Compliant Mechanical Systems. AB - We present a method for the simulation of compliant, articulated structures using a plausible approximate model that focuses on modeling endpoint interaction. We approximate the structure's behavior about a reference configuration, resulting in a first order reduced compliant system, or FORK (-1) S. Several levels of approximation are available depending on which parts and surfaces we would like to have interactive contact forces, allowing various levels of detail to be selected. Our approach is fast and computation of the full structure's state may be parallelized. Furthermore, we present a method for reducing error by combining multiple FORK (-1)S models at different linearization points, through twist blending and matrix interpolation. Our approach is suitable for stiff, articulate grippers, such as those used in robotic simulation, or physics-based characters under static proportional derivative control. We demonstrate that simulations with our method can deal with kinematic chains and loops with non-uniform stiffness across joints, and that it produces plausible effects due to stiffness, damping, and inertia. PMID- 26829236 TI - ClC-7 Deficiency Impairs Tooth Development and Eruption. AB - CLCN7 gene encodes the voltage gated chloride channel 7 (ClC-7) in humans. The mutations in CLCN7 have been associated with osteopetrosis in connection to the abnormal osteoclasts functions. Previously, we found that some osteopetrosis patients with CLCN7 mutations suffered from impacted teeth and root dysplasia. Here we set up two in vivo models under a normal or an osteoclast-poor environment to investigate how ClC-7 affects tooth development and tooth eruption. Firstly, chitosan-Clcn7-siRNA nanoparticles were injected around the first maxillary molar germ of newborn mice and caused the delay of tooth eruption and deformed tooth with root dysplasia. Secondly, E13.5 molar germs infected with Clcn7 shRNA lentivirus were transplanted under the kidney capsule and presented the abnormal changes in dentin structure, periodontal tissue and cementum. All these teeth changes have been reported in the patients with CLCN7 mutation. In vitro studies of ameloblasts, odontoblasts and dental follicle cells (DFCs) were conducted to explore the involved mechanism. We found that Clcn7 deficiency affect the differentiation of these cells, as well as the interaction between DFCs and osteoclasts through RANKL/OPG pathway. We conclude that ClC-7 may affect tooth development by directly targeting tooth cells, and regulate tooth eruption through DFC mediated osteoclast pathway. PMID- 26829239 TI - Diminished Reality Based on Image Inpainting Considering Background Geometry. AB - Diminished reality aims to remove real objects from video images and fill in the missing regions with plausible background textures in real time. Most conventional methods based on image inpainting achieve diminished reality by assuming that the background around a target object is almost planar. This paper proposes a new diminished reality method that considers background geometries with less constraints than the conventional ones. In this study, we approximate the background geometry by combining local planes, and improve the quality of image inpainting by correcting the perspective distortion of texture and limiting the search area for finding similar textures as exemplars. The temporal coherence of texture is preserved using the geometries and camera pose estimated by visual simultaneous localization and mapping (SLAM). The mask region that includes a target object is robustly set in each frame by projecting a 3D region, rather than tracking the object in 2D image space. The effectiveness of the proposed method is successfully demonstrated using several experimental environments. PMID- 26829240 TI - Medial Meshes - A Compact and Accurate Representation of Medial Axis Transform. AB - The medial axis transform has long been known as an intrinsic shape representation supporting a variety of shape analysis and synthesis tasks. However, for a given shape, it is hard to obtain its faithful, concise and stable medial axis, which hinders the application of the medial axis. In this paper, we introduce the medial mesh, a new discrete representation of the medial axis. A medial mesh is a 2D simplicial complex coupled with a radius function that provides a piecewise linear approximation to the medial axis. We further present an effective algorithm for computing a concise and stable medial mesh for a given shape. Our algorithm is quantitatively driven by a shape approximation error metric, and progressively simplifies an initial medial mesh by iteratively contracting edges until the approximation error reaches a predefined threshold. We further demonstrate the superior efficiency and accuracy of our method over existing methods for medial axis simplification. PMID- 26829241 TI - Sticky Projections-A Model-Based Approach to Interactive Shader Lamps Tracking. AB - Shader lamps can augment physical objects with projected virtual replications using a camera-projector system, provided that the physical and virtual object are well registered to each other. Precise registration and tracking has been a cumbersome and intrusive process in the past. In this paper, we present a new method for tracking complex-shaped physical objects interactively. In contrast to previous approaches our system is mobile and makes solely use of the projection of the virtual replication to track the physical object and "stick" the projection to it. Our method consists of two stages, a fast pose initialization based on structured light patterns and a non-intrusive frame-by-frame tracking based on features detected in the projection. During the tracking phase, a radiometrically corrected virtual camera view based on the current pose prediction is rendered and compared to the captured image. Matched features are triangulated providing a sparse set of surface points that is robustly aligned to the virtual model. The alignment transformation serves as an input for the new pose prediction. Detailed experiments including the evaluation of the overlay accuracy show that our approach can accurately and robustly track complex objects at interactive rates. PMID- 26829242 TI - Visualizing and Interacting with Kernelized Data. AB - Kernel-based methods have experienced a substantial progress in the last years, tuning out an essential mechanism for data classification, clustering and pattern recognition. The effectiveness of kernel-based techniques, though, depends largely on the capability of the underlying kernel to properly embed data in the feature space associated to the kernel. However, visualizing how a kernel embeds the data in a feature space is not so straightforward, as the embedding map and the feature space are implicitly defined by the kernel. In this work, we present a novel technique to visualize the action of a kernel, that is, how the kernel embeds data into a high-dimensional feature space. The proposed methodology relies on a solid mathematical formulation to map kernelized data onto a visual space. Our approach is faster and more accurate than most existing methods while still allowing interactive manipulation of the projection layout, a game-changing trait that other kernel-based projection techniques do not have. PMID- 26829243 TI - Self-Assembly of Graphene Nanoblisters Sealed to a Bare Metal Surface. AB - The possibility to intercalate noble gas atoms below epitaxial graphene monolayers coupled with the instability at high temperature of graphene on the surface of certain metals has been exploited to produce Ar-filled graphene nanosized blisters evenly distributed on the bare Ni(111) surface. We have followed in real time the self-assembling of the nanoblisters during the thermal annealing of the Gr/Ni(111) interface loaded with Ar and characterized their morphology and structure at the atomic scale. The nanoblisters contain Ar aggregates compressed at high pressure arranged below the graphene monolayer skin that is decoupled from the Ni substrate and sealed only at the periphery through stable C-Ni bonds. Their in-plane truncated triangular shapes are driven by the crystallographic directions of the Ni surface. The nonuniform strain revealed along the blister profile is explained by the inhomogeneous expansion of the flexible graphene lattice that adjusts to envelop the Ar atom stacks. PMID- 26829244 TI - Separation and determination of flavonoids in three traditional chinese medicines by capillary electrophoresis with amperometric detection. AB - Flavonoids are important active ingredients in many traditional Chinese medicines. In this paper, capillary electrophoresis with amperometric detection was employed to separate and detect eight flavonoids, rutin, quercetrin, quercetin, kaempferol, kaempferide, catechin, apigenin, and luteolin, in a home made capillary electrophoresis device. Under the separation voltage of 2000 V, the eight flavonoids could be completely separated within 33 min in 18 mM borax running buffer at pH 10.2. Good linear relationships were obtained for all analytes and the detection limits for flavonoids ranged from 0.46 to 0.85 MUM. Then, the method was applied to separate and determine the flavonoids in three traditional Chinese medicines, hippophae rhamnoides, hypericum perforatum, and cacumen platycladi. Finally, rutin, kaempferol, quercetin, and quercetrin were discovered in these medicines and the concentrations ranged from 0.28 to 9.94 mg/g. The recoveries of flavonoids ranged from 84.7 to 113%, which showed the high reliability of this method. PMID- 26829245 TI - Evaluation of the Genotoxic and Physiological Effects of Decabromodiphenyl Ether (BDE-209) and Dechlorane Plus (DP) Flame Retardants in Marine Mussels (Mytilus galloprovincialis). AB - Dechlorane Plus (DP) is a proposed alternative to the legacy flame retardant decabromodiphenyl ether (BDE-209), a major component of Deca-BDE formulations. In contrast to BDE-209, toxicity data for DP are scarce and often focused on mice. Validated dietary in vivo exposure of the marine bivalve (Mytilus galloprovincialis) to both flame retardants did not induce effects at the physiological level (algal clearance rate), but induced DNA damage, as determined by the comet assay, at all concentrations tested. Micronuclei formation was induced by both DP and BDE-209 at the highest exposure concentrations (100 and 200 MUg/L, respectively, at 18% above controls). DP caused effects similar to those by BDE-209 but at lower exposure concentrations (5.6, 56, and 100 MUg/L for DP and 56, 100, and 200 MUg/L for BDE-209). Moreover, bioaccumulation of DP was shown to be concentration dependent, in contrast to BDE-209. The results described suggest that DP poses a greater genotoxic potential than BDE-209. PMID- 26829246 TI - Tourniquet Use During Knee Replacement Surgery May Contribute to Muscle Atrophy in Older Adults. AB - Muscle atrophy after total knee arthroplasty (TKA) occurs at a rate of 1% per day for the first 2 wk. Our hypothesis is that tourniquet-induced ischemia reperfusion injury occurring during TKA influences metabolism and may contribute to atrophy. Identifying pathways that are upregulated during this critical "14-d window" after surgery may help us delineate therapeutic approaches to avoid muscle loss. PMID- 26829247 TI - Fiber Type-Specific Effects of Dietary Nitrate. AB - Dietary nitrate supplementation increases circulating nitrite concentration, and the subsequent reduction of nitrite to nitric oxide is promoted in hypoxic environments. Given that PO2 is lower in Type II compared with Type I muscle, this article examines the hypothesis that the ergogenicity of nitrate supplementation is linked to specific effects on vascular, metabolic, and contractile function in Type II muscle. PMID- 26829248 TI - Targeted Health Behavior Interventions Promoting Physical Activity: A Conceptual Model. AB - This article presents a conceptual model illustrating a targeted approach to the design and delivery of health behavior interventions that focus on physical activity promotion. We hypothesize that researchers who i) enhance the sociocultural relevance of their core intervention components and ii) recognize the unique contributions of both intervention design and delivery will experience greater intervention engagement and improved outcomes. PMID- 26829249 TI - Focal effector accumulation in a biotrophic interface at the primary invasion sites of Colletotrichum orbiculare in multiple susceptible plants. AB - We identified virulence-related effectors of a hemibiotrophic fungal pathogen Colletotrichum orbiculare, and found that a novel interface was generated by a biotrophic interaction between C. orbiculare and the host cucumber, in which the effectors secreted from the pathogen accumulated preferentially. The interface was located around the biotrophic primary hyphal neck. Here, we showed that C. orbiculare also developed this interface in a biotrophic interaction with melon, which belongs to Cucurbitaceae. Furthermore, C. orbiculare developed interface in the interaction with a susceptible plant, Nicotiana benthamiana, which is distantly related to Cucurbitaceae, suggesting that the spatial regulation strategy for effectors in C. orbiculare is not specific to cucumber; rather, it is conserved among the various plants that are susceptible to this pathogen. PMID- 26829250 TI - Emulsification-Induced Homohelicity in Racemic Helical Polymer for Preparing Optically Active Helical Polymer Nanoparticles. AB - Optically active nano- and microparticles have constituted a significant category of advanced functional materials. However, constructing optically active particles derived from synthetic helical polymers still remains as a big challenge. In the present study, it is attempted to induce a racemic helical polymer (containing right- and left-handed helices in equal amount) to prefer one predominant helicity in aqueous media by using emulsifier in the presence of chiral additive (emulsification process). Excitingly, the emulsification process promotes the racemic helical polymer to unify the helicity and directly provides optically active nanoparticles constructed by chirally helical polymer. A possible mechanism is proposed to explain the emulsification-induced homohelicity effect. The present study establishes a novel strategy for preparing chirally helical polymer-derived optically active nanoparticles based on racemic helical polymers. PMID- 26829251 TI - Nifedipine GITS/Candesartan Combination Therapy Lowers Blood Pressure Across Different Baseline Systolic and Diastolic Blood Pressure Categories: DISTINCT Study Subanalyses. AB - DISTINCT was an 8-week, double-blind, randomized study to investigate the antihypertensive efficacy and safety of various nifedipine gastrointestinal treatment system (GITS)/candesartan cilexetil (N/C) dose combinations, vs respective monotherapies or placebo, in patients with diastolic blood pressure (DBP) >=95 to <110 mm Hg. The current prespecified analysis compared BP reduction in participants with mild vs moderate baseline hypertension (ie, systolic [S]BP <160 mm Hg vs >=160 mm Hg and DBP <100 mm Hg vs >=100 mm Hg). A total of 1362 patients were analyzed by descriptive statistics. In all patient subgroups investigated, the NC combinations (ie, N: 20, 30, or 60 mg; C: 4, 8, 16, or 32 mg daily) provided greater SBP and DBP lowering and higher rates of BP control (defined as BP <140/90 mm Hg) than respective monotherapies or placebo, with greatest absolute BP reductions observed in the moderately elevated SBP or DBP subgroups. A trend to dose-response relationship was observed in each subgroup. In each SBP and DBP subgroup, treatment-related vasodilatory events (flushing, headache, or edema) were less frequent for patients receiving NC combination therapy than N monotherapy. These analyses support the use of calcium antagonist and angiotensin receptor blocker combination therapy in patients with both mild and moderate hypertension, for whom effective BP normalization and good drug tolerance would greatly reduce the risk of cardiovascular events. PMID- 26829252 TI - Bt proteins Cry1Ah and Cry2Ab do not affect cotton aphid Aphis gossypii and ladybeetle Propylea japonica. AB - Plant varieties expressing the Bt (Bacillus thuringiensis) insecticidal proteins Cry1Ah and Cry2Ab have potential commercialization prospects in China. However, their potential effects on non-target arthropods (NTAs) remain uncharacterized. The cotton aphid Aphis gossypii is a worldwide pest that damages various important crops. The ladybeetle Propylea japonica is a common and abundant natural enemy in many cropping systems in East Asia. In the present study, the effects of Cry1Ah and Cry2Ab proteins on A. gossypii and P. japonica were assessed from three aspects. First, neither of the Cry proteins affected the growth or developmental characteristics of the two test insects. Second, the expression levels of the detoxification-related genes of the two test insects did not change significantly in either Cry protein treatment. Third, neither of the Cry proteins had a favourable effect on the expression of genes associated with the amino acid metabolism of A. gossypii and the nutrition utilization of P. japonica. In conclusion, the Cry1Ah and Cry2Ab proteins do not appear to affect the cotton aphid A. gossypii or the ladybeetle P. japonica. PMID- 26829253 TI - To Use a Rectal Microbicide, First Insert the Applicator: Gel and Applicator Satisfaction Among Young Men Who Have Sex With Men. AB - We examined how experiences with a rectal placebo gel and applicator used with receptive anal intercourse (RAI) related to young men who have sex with men's (YMSM) likelihood of using a rectal microbicide gel and applicator in the future. An ethnically diverse sample of 95 YMSM (aged 18 to 30 years) were asked to insert hydroxyethylcellulose (HEC) placebo gel rectally before RAI during 12 weeks and report the product's acceptability (i.e., satisfaction with applicator and gel, respectively; perceived gel side effects; and sexual satisfaction when gel was used) and likelihood of future microbicide use. Main and interaction effects predicting future use intentions were tested using linear regression. We found a positive association between future use intentions and applicator satisfaction (b = .33, p < .001). In a subsequent interaction effects model, we found that greater gel satisfaction was associated with increased future use intentions; however, the strength of this relationship was magnified when YMSM reported greatest satisfaction with the rectal applicator. Applicator satisfaction may be a salient factor in YMSM's decision-making to use a rectal microbicide in the future. Although the importance of developing a satisfactory rectal microbicide gel for YMSM is undeniable for its future use, our results also emphasize the importance of developing strategies that increase YMSM's comfort and skill when using a rectal applicator. Future research examining how to optimize the design, properties, and characteristics of a rectal applicator as a strategy to promote greater satisfaction and use among YMSM is merited. PMID- 26829254 TI - Assessing Collectivism in Latino, Asian/Pacific Islander, and African American Men Who Have Sex With Men: A Psychometric Evaluation. AB - The study of collectivism has implications for HIV prevention research, especially in studies that use a social networking or community mobilization approach. However, research on collectivism in race/ethnicity and sexual minority groups is limited. We psychometrically evaluated a brief version of the Individualism-Collectivism Interpersonal Assessment Inventory (ICIAI) in a chain referral sample of 400 Latino, 393 Asian/Pacific Islander, and 403 African American men who have sex with men (MSM). Data were collected via a one-time survey on demographics, the ICIAI, acculturation, and ethnicity identity. We conducted a multiple groups confirmatory factor analysis to assess for measurement invariance across the three groups of MSM, as well as tested its reliability and validity. The ICIAI evidenced good psychometric properties and was invariant across all groups. We highlight implications for how this measure of collectivism can be applied toward the study of HIV prevention and in lesbian, gay, bisexual and transgender communities. PMID- 26829255 TI - Association of Situational and Environmental Factors With Last Episode of Unprotected Anal Intercourse Among MSM in Hong Kong: A Case-Crossover Analysis. AB - This study investigates event-specific factors that differentiate the last episodes of unprotected anal intercourse (UAI) from protected anal intercourse (PAI) with regular partner (RP) among 213 men who have sex with men (MSM) who did not use condoms consistently using case-crossover analysis. Factors positively associated with the last episode of UAI with RP included: two situational factors (i.e., participant's suggestion to have UAI, alcohol use) and three environmental/setting factors (i.e., sex took place overseas, during a weekday and not at home). Negative associations with an episode of UAI with RP included: five situational factors (i.e., discussion about condom use prior to sex, RP's suggestion to have PAI, participant's suggestion to have PAI, perception that RP would like to use a condom, participant's planning to use a condom) and two environmental/setting factors (i.e., condoms placed at the venue where sex took place, partner possessed a condom). Thus, these significant event-specific factors explained under which circumstances some MSM would use and would not use condoms during anal sex with RP. PMID- 26829256 TI - Another Way to Talk: Exploring Photovoice as a Strategy to Support Safe Disclosure Among Men and Women With HIV. AB - HIV status disclosure can reduce stigma and facilitate medication adherence and safer sex among people living with HIV (PLH). Effective disclosure interventions are limited, however, and new strategies are necessary. We conducted a pilot Photovoice-based project with 38 PLH in four cities in the Midwest and Northeast U.S. and explored how the project affected disclosure perspectives and experiences. Participants attended three group Photovoice sessions, one individual session, and an optional photo exhibit. Qualitative strategies of theme and narrative analysis of photos and session transcripts revealed that participants discussed three categories of disclosures to others: fearful, reluctant, and open. The project supported all disclosure types, helping fearful participants manage their emotions, reluctant participants plan for more effective disclosures, and open participants share their HIV status. Pilot findings suggest that Photovoice should be further developed and studied as a safe and powerful strategy to improve disclosure and subsequent health and prevention outcomes among PLH. PMID- 26829258 TI - Gender Differences in HIV/AIDS Preventive Self-Efficacy Among Taiwanese Adolescents. AB - The aim of the cross-sectional study was to understand gender differences in HIV/AIDS preventive self-efficacy among Taiwanese adolescents. Self-administered questionnaires were used to measure HIV/AIDS preventive self-efficacy and covariates (age, substance use, and sexual experiences). Data were collected from 734 Taiwanese high school adolescents aged 16 to 18 years. Descriptive statistic analyses, t-test, and ANCOVA were utilized to analyze data. The results indicate significant differences exist between genders in HIV/AIDS preventive self efficacy among Taiwanese adolescents. Compared to the males, female adolescents were found having significantly higher HIV/AIDS preventive self-efficacy related to refusing sexual intercourse, condom use, and questioning potential sexual partners than those who are males. While controlling age, sexual experience, and substance use, female Taiwanese adolescents also had higher HIV/AIDS preventive self-efficacy than those who are males. The findings suggest the importance of addressing gender differences in HIV/AIDS preventive self-efficacy when developing HIV reduction programs for Taiwanese adolescents. PMID- 26829257 TI - Concurrency and Other Sexual Risk Behaviors Among Black Young Adults in a Southeastern City. AB - Black Americans continue to have higher rates of HIV disease than other races/ethnicities. Conventional individual-level risk behaviors do not fully account for these racial/ethnic disparities. Sexual concurrency may help explain them. Respondent-driven sampling (RDS) was used to enroll 508 sexually active 18- to 30-year-old Black men and women in Durham, North Carolina in a cross-sectional survey on HIV-related topics. Consistent condom use was low for all participants, especially with steady partners. Concurrent partnerships in the past 6 months were relatively common for both men (38%) and women (25%). In general, men involved in concurrent relationships engaged in more risk behaviors than other men (e.g., inconsistent condom use and alcohol and drug use). A majority of concurrent partnerships involved steady partners. HIV-prevention programs should address the risks of concurrency and factors that discourage condom use, especially with steady partners with whom condom use is particularly low. PMID- 26829259 TI - Health Care Neglect, Perceived Discrimination, and Dignity-Related Distress Among Chinese Patients With HIV. AB - Dignity-related distress is overlooked in patients with HIV (PHIV). The dignity model, which elucidates the key features of dignity-related distress, has not been applied to the context of stigmatized diseases. By targeting the stigmatized disease of HIV among a Chinese sample, the present study examined the roles of health care neglect and perceived discrimination in dignity-related distress. In this cross-sectional study, 119 Chinese PHIV completed measures of dignity related distress, psychological symptoms, physical symptoms, health care neglect, and perceived discrimination. The results showed that psychological symptoms, physical symptoms, and health care neglect not only independently predicted dignity-related distress, but also moderated with each other to show a three-way interaction. Perceived discrimination also explained the variance in dignity related distress. Our findings contribute to the dignity model by providing evidence for factors associated with dignity-related distress, with focus on HIV. Suggestions to advocate for fair treatment for PHIV and reduce HIV-related discrimination are given. PMID- 26829260 TI - The Role of External Features in Face Recognition with Central Vision Loss. AB - PURPOSE: We evaluated how the performance of recognizing familiar face images depends on the internal (eyebrows, eyes, nose, mouth) and external face features (chin, outline of face, hairline) in individuals with central vision loss. METHODS: In experiment 1, we measured eye movements for four observers with central vision loss to determine whether they fixated more often on the internal or the external features of face images while attempting to recognize the images. We then measured the accuracy for recognizing face images that contained only the internal, only the external, or both internal and external features (experiment 2) and for hybrid images where the internal and external features came from two different source images (experiment 3) for five observers with central vision loss and four age-matched control observers. RESULTS: When recognizing familiar face images, approximately 40% of the fixations of observers with central vision loss was centered on the external features of faces. The recognition accuracy was higher for images containing only external features (66.8 +/- 3.3% correct) than for images containing only internal features (35.8 +/- 15.0%), a finding contradicting that of control observers. For hybrid face images, observers with central vision loss responded more accurately to the external features (50.4 +/- 17.8%) than to the internal features (9.3 +/- 4.9%), whereas control observers did not show the same bias toward responding to the external features. CONCLUSIONS: Contrary to people with normal vision who rely more on the internal features of face images for recognizing familiar faces, individuals with central vision loss show a higher dependence on using external features of face images. PMID- 26829264 TI - Letters to the Editor. PMID- 26829261 TI - Posttraumatic Stress Symptoms and Nonmedical Prescription Drug Use Among College Students With Trauma Exposure. AB - OBJECTIVE: Nonmedical prescription drug use, defined as using the drug without a prescription or in ways for which it is not prescribed, and traumatic event exposure are highly prevalent among college students. Despite evidence that posttraumatic stress symptoms could place college students at risk for nonmedical prescription drug problems, no studies have examined this relationship. This study was a preliminary examination of posttraumatic stress symptoms, lifetime nonmedical prescription drug use, hazardous use, and dependence symptoms among college students with trauma exposure. METHODS: Participants were students attending a rural college in Virginia, recruited through psychology classes, flyers, LISTSERVs, and announcements at student events. All students who reported experiencing at least one traumatic event were included (N = 119); participants' mean age was 19.7 years (SD = 1.90), about half were women (n = 63, 53%), and most were Caucasian (n = 103, 87%). RESULTS: Nearly 60% of participants (n = 71) reported using nonmedical prescription drugs at least once during their lifetime and were more likely than those with no use to report hazardous alcohol use (p < .01) and depressive symptoms (p < .05). There were no other significant differences between those who did and did not report use of nonmedical prescription drugs. Regression analyses showed that posttraumatic stress symptom frequency was positively associated with hazardous nonmedical prescription drug use, after controlling for gender, depressive symptoms, and hazardous alcohol use (p < .001). Posttraumatic stress symptom frequency was higher for those with any nonmedical prescription drug dependence symptoms (p < .001), but was unrelated to whether the student had ever engaged in nonmedical prescription drug use. CONCLUSIONS: Findings suggest that consideration of the types of behaviors and problems a college student is experiencing related to nonmedical prescription drug use may be more relevant to posttraumatic stress symptom frequency than dichotomous measures of nonmedical prescription drug use alone. Further, the association between the frequency of posttraumatic stress symptoms and both hazardous nonmedical prescription drug use and dependence symptoms among college students with a trauma history deserves further investigation due to the resulting vulnerability to increasingly negative outcomes. PMID- 26829265 TI - The role of the US veterinary profession in improving livestock health and productivity and reducing poverty in the developing world. PMID- 26829266 TI - What Is Your Diagnosis?: Neoplasia, intussusception, abscess, granuloma, hematoma, and cyst. PMID- 26829267 TI - Pathology in Practice: severe, multifocal-to-coalescing, histiocytic and lymphoplasmacytic, necrotizing meningoencephalomyelitis. PMID- 26829268 TI - Pathology in Practice: mediastinal lymphoma with hemorrhagic pleural effusion and pulmonary atelectasis in a cat. PMID- 26829270 TI - Factors associated with recovery from paraplegia in dogs with loss of pain perception in the pelvic limbs following intervertebral disk herniation. AB - OBJECTIVE: To investigate associations between recovery of locomotion and putative prognostic factors in dogs with loss of deep pain perception in the pelvic limbs caused by intervertebral disk herniation (IVDH). DESIGN: Prospective cohort study. ANIMALS: 78 client-owned dogs evaluated for IVDH that underwent spinal decompression surgery. PROCEDURES: Dogs with complete loss of deep pain perception in the pelvic limbs and tail underwent routine examinations, advanced imaging, and spinal decompression surgery in accordance with standards of practice and owner consent. For each dog, information was prospectively collected on duration of clinical signs prior to onset of paraplegia; delay between onset of paraplegia and initial referral evaluation; date of recovery of locomotion, death, or euthanasia (3-month follow-up period); and whether dogs had received corticosteroid drugs before surgery. Severity of spinal cord compression at the lesion epicenter was measured via CT or MRI. RESULTS: 45 of 78 (58%) of dogs recovered the ability to ambulate independently within 3 months after spinal decompression surgery. No evidence of prognostic value was identified for any of the investigated factors; importantly, a greater delay between onset of paraplegia and referral evaluation was not associated with a poorer prognosis. CONCLUSIONS AND CLINICAL RELEVANCE: In this group of dogs with IVDH, immediacy of surgical treatment had no apparent association with outcome. The prognosis for recovery may instead be strongly influenced by the precise nature of the initiating injury. PMID- 26829271 TI - Comparison of the efficacy of prednisone and cyclosporine for treatment of dogs with primary immune-mediated polyarthritis. AB - OBJECTIVE: To compare efficacy between cyclosporine and prednisone for treatment of primary immune-mediated polyarthritis (IMPA) in dogs. DESIGN: Randomized controlled clinical trial. ANIMALS: 20 client-owned dogs with primary IMPA. PROCEDURES: Dogs were randomly assigned to receive prednisone (starting at 1 mg/kg [0.45 mg/lb], PO, q 12 h; n = 10) or cyclosporine (5 mg/kg [2.3 mg/lb], PO, q 12 h; 10) for 90 days. Cyclosporine-treated dogs also received carprofen, tramadol, or both for the first 7 days for analgesia. Data collection, physical examination, and cytologic analysis of synovial fluid samples were performed on days 0, 14, 45, and 90. Trough whole blood cyclosporine concentrations were determined on days 7 to 17 for cyclosporine-treated dogs. Treatment failure was defined as lack of clinical improvement by day 14, lack of cytologic improvement by day 45, or need to change treatment because of adverse effects. RESULTS: Treatment was successful for 7 prednisone-treated dogs and 7 cyclosporine-treated dogs. Absence of synovial fluid cytologic abnormalities on day 45 was identified for 5 prednisone-treated dogs and 8 cyclosporine-treated dogs. Prednisone-treated dogs were more likely to develop polyuria, polydipsia, and polyphagia than were cyclosporine-treated dogs. Opportunistic infections (ie, demodicosis or Erysipelothrix bacteremia) were identified in 2 cyclosporine-treated dogs and 0 prednisone-treated dogs, and diarrhea developed in 1 cyclosporine-treated dog, requiring treatment discontinuation. CONCLUSIONS AND CLINICAL RELEVANCE: Although the number of dogs evaluated was small, limiting generalizability, results of this study suggested that cyclosporine offers promise as a suitable alternative to prednisone for treatment of IMPA in dogs. PMID- 26829272 TI - Clinical characterization of thoracolumbar and lumbar intervertebral disk extrusions in English Cocker Spaniels. AB - OBJECTIVE: To assess the anatomic distribution of thoracolumbar and lumbar intervertebral disk extrusions (IVDEs) in English Cocker Spaniels as compared with findings in Dachshunds and to characterize clinical findings in English Cocker Spaniels with thoracolumbar or lumbar IVDEs affecting various regions of the vertebral column. DESIGN: Retrospective observational study. ANIMALS: 81 English Cocker Spaniels and 81 Dachshunds with IVDEs. PROCEDURES: Signalment, clinical signs, neurologic examination findings, and affected intervertebral disk spaces (IVDSs) were recorded for both breeds. Management methods and outcomes were recorded for English Cocker Spaniels. Lesions were categorized as thoracolumbar (IVDSs T9-10 through L1-2), midlumbar (L2-3 through L4-5), or caudal lumbar (L5-6 through L7-S1). RESULTS: Midlumbar and caudal lumbar IVDEs were significantly more common in English Cocker Spaniels than in Dachshunds. English Cocker Spaniels with caudal lumbar IVDEs had a longer median duration of clinical signs before evaluation and more commonly had unilateral pelvic limb lameness or spinal hyperesthesia as the predominant clinical sign than did those with IVDEs at other sites. Those with caudal lumbar IVDEs less commonly had neurologic deficits and had a higher median neurologic grade (indicating lesser severity), shorter mean postoperative hospitalization time, and faster mean time to ambulation after surgery than those with other sites affected. These variables did not differ between English Cocker Spaniels with thoracolumbar and midlumbar IVDEs. CONCLUSIONS AND CLINICAL RELEVANCE: Caudal and midlumbar IVDEs were more common in English Cocker Spaniels than in Dachshunds. English Cocker Spaniels with caudal lumbar IVDE had clinical signs and posttreatment responses that differed from those in dogs with midlumbar or thoracolumbar IVDE. PMID- 26829273 TI - Correction: Pathology in Practice: canine distemper virus infection in a puppy. PMID- 26829274 TI - Ultrasonographic findings and outcomes of dogs with suspected migrating intrathoracic grass awns: 43 cases (2010-2013). AB - OBJECTIVE: To describe ultrasonographic findings and outcomes for dogs with suspected migrating intrathoracic grass awns. DESIGN: Retrospective case series. ANIMALS: 43 client-owned dogs. PROCEDURES: Records for dogs with suspected migrating intrathoracic grass awns examined between 2010 and 2013 were reviewed. Ultrasonographic images and additional information such as signalment and pleural fluid analysis, radiographic, bronchoscopic, and CT findings were collected. Surgical treatments and outcomes were also reviewed. RESULTS: Transthoracic or transesophageal ultrasonography revealed grass awns in the pleural space (n = 13) or pulmonary parenchyma (10) of 23 dogs. Surgical removal of grass awns was successful on the first attempt in 21 of these 23 dogs (including 11/23 that had intraoperative ultrasonography performed to aid localization and removal of the awn). In the remaining 2 dogs, a second surgery was required. Twenty dogs with evidence of migrating intrathoracic grass awns had no foreign body identified on initial ultrasonographic evaluation and were treated medically; 16 developed draining fistulas, and awns identified ultrasonographically at follow-up visits were subsequently removed from the sublumbar region (n = 10) or thoracic wall (6). The remaining 4 dogs had no grass awn visualized. Clinical signs resolved in all dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Transthoracic, transesophageal, and intraoperative ultrasonography were useful for localization and removal of migrating intrathoracic grass awns. Ultrasonography may be considered a valuable and readily available diagnostic tool for monitoring dogs with suspected migrating intrathoracic grass awns. PMID- 26829275 TI - Effect of intraoperative constant rate infusion of lidocaine on short-term survival of dogs with septic peritonitis: 75 cases (2007-2011). AB - OBJECTIVE: To investigate whether intraoperative administration of a lidocaine infusion to dogs with septic peritonitis was associated with short-term (48 hours) survival after surgery. DESIGN: Retrospective case series. ANIMALS: 75 dogs with septic peritonitis. PROCEDURES: Medical records of dogs with septic peritonitis that underwent laparotomy between January 2007 and December 2011 at the Royal Veterinary College were reviewed. Select variables during the preoperative, intraoperative, and postoperative periods and short-term survival after surgery were compared between dogs that received an opioid only (group O; n = 33) and dogs that received lidocaine (50 MUg/kg/min [22.7 MUg/kg/min], IV; group L; 42) in addition to an opioid during surgery. RESULTS: The proportion of dogs that survived for 48 hours after surgery was significantly greater for group L (35/42) than for group O (20/33). Intraoperative infusion of lidocaine increased the odds of short-term survival (OR, 8.77; 95% CI, 1.94 to 39.57). No significant differences were observed between the 2 treatment groups for variables assessed during the preoperative and postoperative periods. During the intraoperative period, more dogs in group L received an IV bolus of a synthetic colloid than did dogs in group O, but the number of IV boluses administered was not associated with short-term survival. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that IV infusion of lidocaine might improve the short-term survival of dogs with septic peritonitis. Prospective clinical trials are necessary to determine the efficacy of lidocaine as a supportive treatment for dogs with septic peritonitis. PMID- 26829276 TI - Ventricular pneumocephalus, cervical subarachnoid pneumorrhachis, and meningoencephalitis in a dog following rhinotomy for chronic fungal rhinitis. AB - CASE DESCRIPTION: A 5-year-old 35.8-kg (78.8-lb) neutered male Labrador Retriever was evaluated for chronic nasal discharge associated with a fungal infection. The dog had previously been prescribed antimicrobials and antifungal treatment, but owner compliance was lacking. CLINICAL FINDINGS: Bilateral mucopurulent nasal discharge, mild ulceration of the left nasal commissure, and hyperkeratosis of the dorsal nasal planum were present. Computed tomography revealed destruction of the intranasal structures, focal lysis of the cribriform plate, and invasion of a soft-tissue mass into the frontal cortex. Rhinoscopy revealed a large pale mass in the caudal aspect of the right nasal passage; a biopsy sample was consistent with Aspergillus sp on histologic evaluation. TREATMENT AND OUTCOME: Initial treatment included medical management with an antifungal agent. Approximately 3 months later, a large fungal granuloma in the right frontal sinus was removed and debridement was performed via dorsal rhinotomy. One month after surgery, the dog was evaluated for signs of cervical pain and altered mentation. An MRI and CSF analysis were performed; diagnoses of ventricular pneumocephalus, subarachnoid pneumorrhachis, and meningoencephalitis were made. Management included oxygen therapy and administration of antimicrobials, analgesics, and antifungal medications. On follow-up 9 months after initial evaluation, neurologic deficits were reportedly resolved, and the dog was doing well. CONCLUSIONS AND CLINICAL RELEVANCE: This report emphasizes the importance of prompt, appropriate treatment of fungal rhinitis in dogs. Although rare, pneumocephalus and pneumorrhachis should be included as differential diagnoses for neurologic signs following treatment for this condition. In this dog, the complications were not considered severe and improved over time with supportive care. PMID- 26829277 TI - Pertinent parameters in photo-generation of electrons: Comparative study of anatase-based nano-TiO2 suspensions. AB - In the field of solar fuel cells, the development of efficient photo-converting semiconductors remains a major challenge. A rational analysis of experimental photocatalytic results obtained with material in colloidal suspensions is needed to access fundamental knowledge required to improve the design and properties of new materials. In this study, a simple system electron donor/nano-TiO2 is considered and examined via spin scavenging electron paramagnetic resonance as well as a panel of analytical techniques (composition, optical spectroscopy and dynamic light scattering) for selected type of nano-TiO2. Independent variables (pH, electron donor concentration and TiO2 amount) have been varied and interdependent variables (aggregate size, aggregate surface vs. volume and acid/base groups distribution) are discussed. This work shows that reliable understanding involves thoughtful combination of interdependent parameters, whereas the specific surface area seems not a pertinent parameter. The conclusion emphasizes the difficulty to identify the key features of the mechanisms governing photocatalytic properties in nano-TiO2. PMID- 26829278 TI - Neuropsychological performance of Finnish and Egyptian children with autism spectrum disorder. AB - BACKGROUND: Previous studies investigating neuropsychological functioning of children with autism spectrum disorder (ASD) have only analysed certain abilities, such as executive functions or language. While comprehensive assessment of the neuropsychological profile of children with ASD has been the focus of recent research, most of the published evidence originates from single centres. Though studies on differences in neuropsychological features of children with ASD across countries are essential for identifying different phenotypes of ASD, such studies have not been conducted. OBJECTIVE: Our goal was to assess the neuropsychological abilities of children with ASD in northern Finland and Egypt and to examine the effect of age and intelligence quotient (IQ) on these abilities. DESIGN: Selected verbal and non-verbal subtests of the neuropsychological assessment NEPSY were used to examine 88 children with ASD in northern Finland (n=54, age M=11.2, IQ M=117.1) and Egypt (n=34, age M=8.4, IQ M=96.6). RESULTS: Finnish ASD children scored significantly higher than their Egyptian counterparts on the verbal NEPSY subtests Comprehension of Instructions (p<0.001), Comprehension of Sentence Structure (p<0.01), Narrative Memory (p<0.001) and Verbal Fluency (p<0.05) and on the non-verbal NEPSY subtest Design Fluency (p<0.01). Finnish and Egyptian ASD children did not differ on the subtests Memory for Faces, Object Recognition and Object Memory. In addition, we found that age and verbal IQ can have significant influence on neuropsychological performance. CONCLUSIONS: Our results suggest a possible cultural impact on verbal and visuomotor fluency. However, the ability to recognize and memorize objects and the disability to remember faces appear to be typical for ASD and culturally independent. PMID- 26829279 TI - A cohort study of chronic diseases for Mongolian people: Outline with baseline data of the Moncohort study. AB - Many Mongolian people suffer from non-communicable chronic diseases. In order to plan preventive strategies against such diseases, we designed a community-based prospective cohort study of chronic diseases, called the Moncohort study, in Mongolia. This is the first nationwide large-scale cohort study of chronic diseases. This paper describes the study's rationale, design and methods with baseline data. Mongolian residents aged ?40years were selected nationwide from many geographic regions in 2009. Data were collected on demographics, socioeconomic status, lifestyle, and anthropometric and biochemical measurements. In total, 2280 Mongolian residents were registered in the survey. Socioeconomic, lifestyle, anthropometric and biochemical characteristics were differentiated by gender and geographical area in descriptive data. Aging, low social class, physical inactivity and infrequent fruits intake were positively associated with histories of chronic disease in men, while aging was positively associated with histories of chronic disease in women. Factors associated with chronic diseases reveal gender-oriented strategies might be needed for their prevention. Detailed prospective analyses will illustrate the impact of risk factors on chronic diseases and lead to evidence for designing programs aimed at preventing chronic diseases and related disorders in Mongolia. PMID- 26829280 TI - Novel 4-anilinoquinazoline derivatives featuring an 1-adamantyl moiety as potent EGFR inhibitors with enhanced activity against NSCLC cell lines. AB - With the aim of overcoming gefitinib resistance, a series of novel quinazoline derivatives bearing an adamantyl group on the aniline ring were synthesized as potent epidermal growth factor receptor (EGFR) inhibitors. Most of these analogues are comparable to gefitinib in their ability to inhibit non-small cell lung cancer (NSCLC) cell lines, and several also exhibited significantly enhanced anti-tumor potency. Specifically, compound 3d, with an IC50 value of 2.06 MUM against A431 cells with the wild-type EGFR and of 0.009 MUM against the gefitinib sensitive cells, displayed approximately 5-fold higher potency than the lead compound to inhibit the cells harboring the EGFR(T790M) mutant. In addition, the molecular simulation and Western blot analysis results also indicated that these compounds effectively interfered with the EGFR(T790M) activity, and may serve as a new alternative structure to develop more effective antitumor agents. PMID- 26829281 TI - Foetal and neonatal intracranial haemorrhage in term newborn infants: Hacettepe University experience. AB - In this study, we aimed to evaluate the incidence, risk factors, causes and clinical management of intracranial haemorrhage (ICH) diagnosed during foetal life or in the first month of life in term neonates with a discussion of the role of haematological risk factors. This study included term neonates (gestational age 37-42 weeks) with ICH diagnosed, treated and followed up in the Neonatal Intensive Care Unit of Hacettepe University, Ankara, Turkey, between January 1994 and January 2014. Medical follow-up was obtained retrospectively from hospital files and prospectively from telephonic interviews and/or clinical visits. During the study period, 16 term neonates were identified as having ICH in our hospital. In six (37.5%) neonates, ICH was diagnosed during foetal life by obstetric ultrasonography, and in 10 (62.5%) neonates, it has been diagnosed after birth. Haemorrhage types included intraventricular haemorrhage (IVH) in eight (50.0%), intraparenchymal haemorrhage in six (37.5%), subarachnoid haemorrhage in one (6.2%) and subdural haemorrhage in one (6.2%) neonate. IVH was the most common (n = 5/6, 83.3%) haemorrhage type among neonates diagnosed during foetal life. Overall, haemorrhage severity was determined as mild in three (18.7%) neonates, moderate in three (18.75%) neonates and severe in 10 (62.5%) neonates. During follow-up, one infant was diagnosed as afibrinogenemia, one diagnosed as infantile spasm, one cystic fibrosis, one orofaciodigital syndrome and the other diagnosed as Friedrich ataxia. Detailed haematological investigation and search for other underlying diseases are very important to identify the reason of ICH in term neonates. Furthermore, early diagnosis, close monitoring and prompt surgical interventions are significant factors to reduce disabilities. PMID- 26829282 TI - Coagulation, thrombophilia and patency of arteriovenous fistula in children undergoing haemodialysis compared with healthy volunteers: a prospective analysis. AB - This study aimed to assess whether markers of coagulation, fibrinolysis or thrombophilia are increased in children on haemodialysis compared with controls and whether measurement of any of these factors could help to identify patients at an increased risk of arteriovenous fistula (AVF) occlusion. Blood samples were taken from 55 children immediately before a session of haemodialysis and from 20 healthy volunteers. Thrombin-antithrombin (TAT), D-dimer, plasmin-antiplasmin (PAP) and anticardiolipin immunoglobulin G (ACA-Ig G) were measured by ELISA. Factor V Leiden mutation (G1691A) was determined by gene polymorphism [restriction fragment length polymorphism (RFLP)]. Determination of the patency of the AVF was prospectively followed up for a minimum of 4 years or until the AVF was nonfunctioning. Fifty-five patients were studied with a median follow-up of 659 days (range 30-1670 days). A significant increase was found in the levels of D-dimer, PAP and ACA-Ig G in haemodialysis patients with thrombosed and nonthrombosed native AVFs vs. CONTROLS: There was a significant difference between both chronic haemodialysis patients with thrombosed and nonthrombosed native AVF with regard to ACA-IgG levels. At 1 year follow-up, primary patency was 61.4% (27 patients). In multivariate analysis, D-dimer was inversely associated with secondary patency.Thrombophilia may predispose children with end stage renal disease to access failure. The promising finding is that in children on haemodialysis, D-dimer levels were increased and inversely correlated with secondary patency. Further evaluation is required into the possible role of D dimer as a biomarker of AVF occlusion. PMID- 26829283 TI - Assessment of rotation thromboelastometry parameters in patients with essential thrombocythemia at diagnosis and after hydroxyurea therapy. AB - Patients with essential thrombocythemia suffer from thrombotic complications that are the main source of mortality. Due to its complex pathogenesis, no existing single laboratory method is able to identify the patients at highest risk for developing thrombosis. Twenty patients with essential thrombocythemia at diagnosis, 15 healthy volunteers and 20 patients treated with hydroxyurea were compared with regard to certain rotation thromboelastometry parameters. Clotting time (CT), clot formation time (CFT), alpha-angle, and maximum clot firmness (MCF) were assessed by using the INTEM, EXTEM, FIBTEM, and NATEM tests. Patients with essential thrombocythemia at diagnosis demonstrated significantly higher mean platelet count and markedly lower mean red blood count than controls. CT and CFT readings were found to be markedly lower in essential thrombocythemia patients at diagnosis than in the control group according to the EXTEM test. Patients at diagnosis had markedly lower CT values (EXTEM, FIBTEM) than patients on hydroxyurea therapy. Alpha angle values were markedly higher in essential thrombocythemia patients at diagnosis than in controls, according to the EXTEM, FIBTEM and NATEM tests. MCF readings were significantly higher in essential thrombocythemia patients at diagnosis than in controls according to EXTEM, INTEM, FIBTEM, and NATEM tests. Patients on hydroxyurea therapy had markedly lower MCF values according to EXTEM test than patients at diagnosis. Patients with essential thrombocythemia demonstrate a prothrombotic state at the time of diagnosis, which is reflected in changes by certain rotation thromboelastometry parameters. The hydroxyurea therapy induces downregulation of the prothrombotic features seen in essential thrombocythemia patients at diagnosis. PMID- 26829284 TI - The Role of Impulsivity in the Relation Between Negative Affect and Risky Sexual Behaviors. AB - While risky sexual behavior associates with negative affect, and impulsivity often increases during negative affective states, little is known about the interrelations of these factors. This study examined whether impulsivity explained the relation between negative affect and risky sex among college students. Negative affect exhibited an indirect effect via impulsivity on number of sexual partners for both males and females, and on inconsistent condom use for females, but not males. Results suggest risky sex may serve to regulate negative affect, proposing the importance of negative affect in future strategies to reduce risky sex among young adults. PMID- 26829286 TI - Corynebacterium glutamicum Metabolic Engineering with CRISPR Interference (CRISPRi). AB - Corynebacterium glutamicum is an important organism for the industrial production of amino acids. Metabolic pathways in this organism are usually engineered by conventional methods such as homologous recombination, which depends on rare double-crossover events. To facilitate the mapping of gene expression levels to metabolic outputs, we applied CRISPR interference (CRISPRi) technology using deactivated Cas9 (dCas9) to repress genes in C. glutamicum. We then determined the effects of target repression on amino acid titers. Single-guide RNAs directing dCas9 to specific targets reduced expression of pgi and pck up to 98%, and of pyk up to 97%, resulting in titer enhancement ratios of l-lysine and l glutamate production comparable to levels achieved by gene deletion. This approach for C. glutamicum metabolic engineering, which only requires 3 days, indicates that CRISPRi can be used for quick and efficient metabolic pathway remodeling without the need for gene deletions or mutations and subsequent selection. PMID- 26829288 TI - Nanomedicine in the development of anti-HIV microbicides. AB - Prevention plays an invaluable role in the fight against HIV/AIDS. The use of microbicides is considered an interesting potential approach for topical pre exposure prophylaxis of HIV sexual transmission. The prospects of having an effective product available are expected to be fulfilled in the near future as driven by recent and forthcoming results of clinical trials. Different dosage forms and delivery strategies have been proposed and tested for multiple microbicide drug candidates presently at different stages of the development pipeline. One particularly interesting approach comprises the application of nanomedicine principles to the development of novel anti-HIV microbicides, but its implications to efficacy and safety are not yet fully understood. Nanotechnology-based systems, either presenting inherent anti-HIV activity or acting as drug nanocarriers, may significantly influence features such as drug solubility, stability of active payloads, drug release, interactions between active moieties and virus/cells, intracellular drug delivery, drug targeting, safety, antiviral activity, mucoadhesive behavior, drug distribution and tissue penetration, and pharmacokinetics. The present manuscript provides a comprehensive and holistic overview of these topics as relevant to the development of vaginal and rectal microbicides. In particular, recent advances pertaining inherently active microbicide nanosystems and microbicide drug nanocarriers are discussed. PMID- 26829289 TI - Microbicide vaginal rings: Technological challenges and clinical development. AB - Vaginal rings (VRs) are flexible, torus-shaped, polymeric devices designed to sustain delivery of pharmaceutical drugs to the vagina for clinical benefit. Following first report in a 1970 patent application, several steroid-releasing VR products have since been marketed for use in hormone replacement therapy and contraception. Since 2002, there has been growing interest in the use of VR technology for delivery of drugs that can reduce the risk of sexual acquisition of human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS). Although no vaginally-administered product has yet been approved for HIV reduction/prevention, extensive research efforts are continuing and a number of VR devices offering sustained release of so-called 'HIV microbicide' compounds are currently being evaluated in late-stage clinical studies. This review article provides an overview of the published scientific literature within this important field of research, focusing primarily on articles published within peer-reviewed journal publications. Many important aspects of microbicide-releasing VR technology are discussed, with a particular emphasis on the technological, manufacturing and clinical challenges that have emerged in recent years. PMID- 26829287 TI - Targeted pulmonary delivery of inducers of host macrophage autophagy as a potential host-directed chemotherapy of tuberculosis. AB - One of the promising host-directed chemotherapeutic interventions in tuberculosis (TB) is based on inducing autophagy as an immune effector. Here we consider the strengths and weaknesses of potential autophagy-based pharmacological intervention. Using the existing drugs that induce autophagy is an option, but it has limitations given the broad role of autophagy in most cells, tissues, and organs. Thus, it may be desirable that the agent being used to modulate autophagy is applied in a targeted manner, e.g. delivered to affected tissues, with infected macrophages being an obvious choice. This review addresses the advantages and disadvantages of delivering drugs to induce autophagy in M. tuberculosis-infected macrophages. One option, already being tested in models, is to design particles for inhalation delivery to lung macrophages. The choice of drugs, drug release kinetics and intracellular residence times, non-target cell exposure and feasibility of use by patients is discussed. We term here this (still experimental) approach, of compartment-targeting, autophagy-based, host directed therapy as "Track-II antituberculosis chemotherapy." PMID- 26829290 TI - Genistein ameliorated endothelial nitric oxidase synthase uncoupling by stimulating sirtuin-1 pathway in ox-LDL-injured HUVECs. AB - Endothelial nitric oxidase synthase (eNOS) uncoupling plays a causal role in endothelial dysfunction in atherosclerosis. Genistein consumption has been associated with the prevention of atherosclerosis. However, the effect of genistein on eNOS uncoupling has not been reported. A model of oxidized low density lipoprotein (ox-LDL)-induced injury on human umbilical vein endothelial cells (HUVECs) was established to evaluate the effect of genistein on eNOS uncoupling. We investigated the effect of genistein on NADPH oxidase-dependent superoxide production, NOX4 expression, BH4 synthesis and oxidation, the expression of GTP cyclohydrolase 1 (GCH1) and dihydrofolate reductase (DHFR). The results showed that genistein decreased superoxide production and NOX4 expression, enhanced the ratio of BH4/BH2, augmented the expressions of GCH1 and DHFR. Accompanied with genistein ameliorating eNOS uncoupling, genistein elevated the expression of sirtuin-1; furthermore, the effects of genistein on eNOS uncoupling were blunted with sirtuin-1 siRNA. The present study indicated that genistein ameliorated eNOS uncoupling was concerned with sirtuin-1 pathway in ox LDL-injured HUVECs. PMID- 26829291 TI - Coupling Hollow Fe3O4-Fe Nanoparticles with Graphene Sheets for High-Performance Electromagnetic Wave Absorbing Material. AB - We developed a strategy for coupling hollow Fe3O4-Fe nanoparticles with graphene sheets for high-performance electromagnetic wave absorbing material. The hollow Fe3O4-Fe nanoparticles with average diameter and shell thickness of 20 and 8 nm, respectively, were uniformly anchored on the graphene sheets without obvious aggregation. The minimal reflection loss RL values of the composite could reach 30 dB at the absorber thickness ranging from 2.0 to 5.0 mm, greatly superior to the solid Fe3O4-Fe/G composite and most magnetic EM wave absorbing materials recently reported. Moreover, the addition amount of the composite into paraffin matrix was only 18 wt %. PMID- 26829292 TI - Mongolians in the Genetic Landscape of Central Asia: Exploring the Genetic Relations among Mongolians and Other World Populations. AB - Genetic data on North and Central Asian populations are underrepresented in the literature, especially for autosomal markers. In the present study we used 812 single nucleotide polymorphisms (SNPs) distributed across all the human autosomes and extensively studied at Yale to examine the affinities of two recently collected samples of populations: rural and cosmopolitan Mongolians from Ulaanbaatar and nomadic, Turkic-speaking Tsaatan from Mongolia near the Siberian border. We compare these two populations with each other and with a global set of populations and discuss their relationships to New World populations. Specifically, we analyze data on 521 autosomal loci (single SNPs and multi-SNP haplotypes) studied in 57 populations representing all the major geographical regions of the world. We conclude that these North and Central Asian populations are genetically distinct from all other populations in our study and may be close to the ancestral lineage leading to the New World populations. PMID- 26829293 TI - Evolution and Otitis Media: A Review, and a Model to Explain High Prevalence in Indigenous Populations. AB - Otitis media (OM; inflammation of the middle ear) comprises a group of disorders that are among the most common disorders of childhood. OM is also heritable and has effects on fecundity. This means that OM is subject to evolution, yet the evolutionary forces that may determine susceptibility to OM have not been adequately explored. Here I analyze evolutionary forces that may determine susceptibility to middle ear inflammation. These forces include those affecting function of the middle ear, host immunity, or colonization by and pathogenicity of bacteria. I review existing evolutionary models of host-pathogen interaction and coevolution and apply these to better understand the complex evolutionary landscape of middle ear infection and inflammation in humans, including factors determining transition between stable evolutionary strategies for host and bacteria. This understanding is then applied to an analysis of OM in indigenous populations to devise a new theory for OM prevalence in Australian Aborigine, Native American, Inuit, and Maori populations. I suggest that high prevalence in such groups may have resulted from encounters of these previously isolated populations with European immigrants in the 15th and 16th centuries. This exposed them to new strains of bacteria to which their immune system had not evolved immunity, perturbing a previously stable host-pathogen coevolutionary state. PMID- 26829294 TI - Origins of an Unmarked Georgia Cemetery Using Ancient DNA Analysis. AB - Determining the origins of those buried within undocumented cemeteries is of incredible importance to historical archaeologists and, in many cases, the nearby communities. In the case of Avondale Burial Place, a cemetery in Bibb County, Georgia, in use from 1820 to 1950, all written documentation of those interred within it has been lost. Osteological and archaeological evidence alone could not describe, with confidence, the ancestral origins of the 101 individuals buried there. In the present study, we used ancient DNA extraction methods in well preserved skeletal fragments from 20 individuals buried in Avondale Burial Place to investigate the origins of the cemetery. Through examination of hypervariable region I (HVR1) in the mitochondrial genome (mtDNA), we determined haplotypes for all 20 of these individuals. Eighteen of these individuals belong to the L or U haplogroups, suggesting that Avondale Burial Place was most likely used primarily as a resting place for African Americans. After the surrounding Bibb County community expressed interest in investigating potential ancestral relationships to those within the cemetery, eight potential descendants provided saliva to obtain mtDNA HVR1 information. Three individuals from Avondale Burial Place matched three individuals with oral history ties to the cemetery. Using the online tool EMPOP, we calculated the likelihood of these exact matches occurring by chance alone (< 1%). The present findings exhibit the importance of genetic analysis of cemetery origins when archaeological and osteological data are inconclusive for estimating ancestry of anonymous historical individuals. PMID- 26829295 TI - Influence of Changes in Political Barriers and of Geographic Distance on Kinship Inferred from Surnames and Migration Data in Olivenza, Spain, and Surrounding Portuguese Areas. AB - The existing relationship between human populations is a function of their migratory and genetic exchange, which will be inversely proportional to the distance separating them. The effect of geographic distance on population structure may be estimated by means of isonymic methods that use information on the surnames present in a territory as an approximation to the distribution of allele frequencies. The objective of this study was to analyze whether the 1801 modification of the political border in an area surrounding the town of Olivenza, which experienced a change of sovereignty from Portugal to Spain, has had a noticeable influence on the migration pattern and isolation by distance in that region. For this purpose, data from marriage records of Olivenza and the neighboring Portuguese municipalities of Alandroal, Juromenha, Elvas, Vila Boim (and Terrugem), Terena, Monsaraz, and Vila Vicosa were analyzed. Rates of diversity and inbreeding coefficients were determined to analyze the population structure before (1775-1801) and after (1802-1825) the change of domain. The results show that after the border modification the migration matrices changed differently according to sex, therefore altering the relationship between the various localities of the territory. In Olivenza inbreeding declined slightly and surnames became more heterogeneous. Moreover, after the change of domain the isolation-by-distance models illustrate a temporal reduction in the relative weight of geographical distance on interpopulation kinship. The political border acted as a factor in population differentiation in the Iberian Peninsula (Spain and Portugal). PMID- 26829296 TI - Genome of the Ancient One (a.k.a. Kennewick Man). PMID- 26829298 TI - Idiopathic granulomatous mastitis: Long-discussed but yet-to-be-known. AB - Idiopathic granulomatous mastitis (IGM) is a chronic benign inflammatory disease of the breast with unknown etiology. It is an important diagnostic and therapeutic challenge, as most patients were initially misdiagnosed by their primary care physicians, leading to diagnostic confusion and heightened anxiety. Although several triggers have been proposed for development of IGM, the etiologic association of neither of them has been documented. Three main hypotheses about the possible causes of IGM have been suggested, including autoimmune response, infectious disease, and hormonal disruption. Here, we discuss a hypothetical perspective of IGM to explain the possible role of autoinflammation in the pathogenesis of the disease. We also reviewed the previously published literature on pathogenesis of IGM. PMID- 26829300 TI - A Rare Cause of Recurrent Hematochezia. PMID- 26829301 TI - Pancreatic Cyst After Trauma in a Young Female. PMID- 26829302 TI - An Uncommon Destination of Routine Esophagogastroduodenoscopy. PMID- 26829303 TI - A Patient With Left Upper Abdominal Pain Who Had Petit Sac. PMID- 26829304 TI - A Rare Cause of Multiple Intestinal Mass Lesions. PMID- 26829305 TI - Comparative proteomics of Acidithiobacillus ferrooxidans grown in the presence and absence of uranium. AB - Acidithiobacillus ferrooxidans is an acidophile that thrives in metal contaminated environments and tolerates high levels of uranium. To gain a better understanding of the processes involved in U(VI) resistance, comparative proteomics was used. The proteome of A. ferrooxidans was grown in the presence and absence of 0.5 mM U(VI); expression of 17 proteins was upregulated and one was downregulated. Most proteins with increased expression are part of the general stress response or are involved in reactive oxygen species detoxification. Four novel proteins showed increased expression in the presence of U(VI) and may contribute to U(VI) resistance via thiol homoeostasis and U(VI) binding. PMID- 26829306 TI - Elucidation of the functional role of flagella in virulence and ecological traits of Pseudomonas cichorii using flagella absence (DeltafliJ) and deficiency (DeltafliI) mutants. AB - Understanding the infection mechanisms of pathogens will lead to better management of the associated diseases. The flagella of these pathogens play significant roles not only in bacterial motility, but also in virulence. In the present study, two genes involved in flagella construction, fliJ and fliI of Pseudomonas cichorii, were analyzed. The results revealed that these genes are vital for flagella formation and play significant roles not only in motility, but also in virulence. When we inoculated host plants with fliI- and fliJ-defective mutants (DeltafliJ and DeltafliI) through the dipping method, the degree of disease severity caused by both mutants was significantly reduced compared to those of the wild-type. However, the virulence of DeltafliI was stronger than that of DeltafliJ. Electron microscope observation, and swarming and leaf attachment assays indicated a reduced number of flagella in DeltafliI, but not complete absence, because of the presence of another copy of fliI. Furthermore, a vacuum infiltration assay revealed that flagella are indispensable in the pre- and post-penetration stages for complete virulence. Overall, we created semi defective (DeltafliI) and completely defective (DeltafliJ) mutants and elucidated the fact that flagella play significant roles in virulence of the pathogen at different stages of the infection process. PMID- 26829307 TI - Assessment of health risk from organochlorine xenobiotics in goat milk for consumers in Poland. AB - The occurrence of organochlorine xenobiotics in goat milk is a one of bioindicators of environmental pollution, and, consequently, food contamination. This study estimates contamination level of goat milk produced at two organic farms in years 2009-2013. Analysis covered determination of 18 organochlorine pesticides, including HCH isomers (alpha, beta, gamma, delta), DDT and its metabolites, endosulfan and its derivatives, and methoxychlor. Pesticide content was determined using GCMS method. The detected levels of organochlorine residues in goat milk were low, in most cases below 8 ng g(-1) lipids. Among HCH isomers, gamma- and beta-HCH occurred in the highest concentrations, up to 4.85 ng g(-1) lipids. While among DDT metabolites p,p'-DDD dominated, up to 7.86 ng g(-1) lipids. The detected residues were below the current maximum residue limits (MRLs) for the pesticides. Considering the average milk consumption in Poland, the goat milk from both farms was safe for consumers' health. The lifetime average daily dose (LADD) for the sum of the compounds under study ranged within 1.73 * 10(-5)-1.06 * 10(-4) mg kg bw(-1) d(-1) and were well below the acceptable daily intake (ADI) for particular compounds. This was also confirmed by the values of hazard quotient (HQ), which were very low and ranged within 3.42 * 10( 3)-5.55 * 10(-2). PMID- 26829308 TI - Feasibility of enhancing the DEnitrifying AMmonium OXidation (DEAMOX) process for nitrogen removal by seeding partial denitrification sludge. AB - The recently proposed DEnitrifying AMmonium OXidation (DEAMOX) process combined anaerobic ammonia oxidation (ANAMMOX) with denitrification to convert nitrate to nitrite, which was a promising way for treating wastewater containing nitrate and ammonia. This study investigated the feasibility of establishing DEAMOX process by seeding partial denitrification sludge (NO3(-) -> NO2(-)) using sodium acetate as an electron donor in a sequencing batch reactor. Results showed that the DEAMOX process was established successfully and operated stably in 114-days operation. The average effluent total nitrogen concentration was below 5 mg L(-1) and TN removal efficiency reached up to 97% at COD/NO3(-) ratio of 3.0 under initial NH4(+) concentration of 25 mg L(-1) and NO3(-) of 30 mg L(-1). It suggested that the presence of NO2(-) in the system supplied for ANAMMOX and the relatively long sludge retention time (SRT) for denitrifiers were attributed to commendable coexistence of ANAMMOX and denitrifying bacteria. PMID- 26829309 TI - Children with health impairments by heavy metals in an e-waste recycling area. AB - E-waste recycling has become a global environmental health issue. Pernicious chemicals escape into the environment due to informal and nonstandard e-waste recycling activities involving manual dismantling, open burning to recover heavy metals and open dumping of residual fractions. Heavy metals derived from electronic waste (e-waste), such as, lead (Pb), cadmium (Cd), chromium (Cr), manganese (Mn), nickel (Ni), mercury (Hg), arsenic (As), copper (Cu), zinc (Zn), aluminum (Al) and cobalt (Co), differ in their chemical composition, reaction properties, distribution, metabolism, excretion and biological transmission. Our previous studies showed that heavy metal exposure have adverse effects on children's health including lower birth weight, lower anogenital distance, lower Apgar scores, lower current weight, lower lung function, lower hepatitis B surface antibody levels, higher prevalence of attention-deficit/hyperactivity disorder, and higher DNA and chromosome damage. Heavy metals influence a number of diverse systems and organs, resulting in both acute and chronic effects on children's health, ranging from minor upper respiratory irritation to chronic respiratory, cardiovascular, nervous, urinary and reproductive disease, as well as aggravation of pre-existing symptoms and disease. These effects of heavy metals on children's health are briefly discussed. PMID- 26829310 TI - Cerebrovascular reactivity and neurovascular coupling in patients with obstructive sleep apnea. AB - AIM: Obstructive sleep apnea syndrome (OSAS) has been implicated as an independent risk factor for stroke. There are data suggesting the presence of lower cerebrovascular reactivity (CVR) as determined by transcranial Doppler (TCD) in patients with OSAS. We concurrently investigated neurovascular coupling (NVC) with visual stimulation, and CVR using breath-holding (BH) test on TCD in patients with OSAS. MATERIALS AND METHODS: Data were collected in 49 patients with moderate to severe OSAS, and compared to 15 healthy subjects matched for age and risk factors. The CVR to hypercapnia was measured by BH test, and the NVC was performed with visual stimulation. RESULTS: There were no significant differences in baseline characteristics of patients and controls, except for BMI, which was significantly higher in patients with OSAS (p = 0.036). OSAS patients showed significantly lower reactivity during BH in comparison to controls (36.9% +/- 14.0% vs. 46.6% +/- 20.1%; p = 0.019). The reactivity time was also significantly shorter in the OSAS group (8.0 +/- 4.2 s) when compared to controls (10.1 +/- 4.3 s; p = 0.015). The visual stimulation produced similar reactivity in patients (27.7% +/- 9.4%) and controls (29.1 +/- 13.9; p > 0.05). CONCLUSIONS: Our data demonstrate a diminished vasodilator response capacity only to a strong stimulator such as hypercapnia in OSAS patients. However, the NVC, as shown by the TCD, is quite normal, suggesting that a weak or mild stimulation produces a proper reactivity among OSAS patients. PMID- 26829311 TI - KRAS and NKX2-1 Mutations in Invasive Mucinous Adenocarcinoma of the Lung. AB - INTRODUCTION: Mucinous differentiation is observed in a subset of lung adenocarcinomas with unique clinical and pathological features, but the biology of these neoplasms is poorly understood. METHODS: We apply targeted next generation sequencing to characterize the mutational profiles of 21 invasive mucinous adenocarcinomas, mixed mucinous/nonmucinous adenocarcinomas, and adenocarcinomas with mucinous features of the lung and validate key findings on 954 additional lung adenocarcinomas from our institution and 514 lung adenocarcinomas from The Cancer Genome Atlas. RESULTS: Sequencing identifies pathogenic mutations in the oncogenes Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), erb-b2 receptor tyrosine kinase 2 (ERBB2), and anaplastic lymphoma receptor tyrosine kinase (ALK) and recurrent mutations in tumor protein p53 (TP53), serine/threonine kinase 11 (STK11), NK2 homeobox 1 (NKX2-1), and SET domain containing 2 (SETD2). In the combined discovery and validation cohorts, we identify nine neoplasms with distinct molecular and pathological features. All are invasive mucinous adenocarcinomas or mixed mucinous/nonmucinous adenocarcinomas with mutations of KRAS and frameshift or nonsense mutations of NKX2-1. Immunohistochemical analysis shows that these neoplasms are associated with altered differentiation states, including loss of expression of the pulmonary marker thyroid transcription factor 1 (also called Nkx2.1) and expression of gastrointestinal markers. CONCLUSIONS: These findings describe recurrent NKX2-1 mutations in invasive mucinous adenocarcinomas of the lung and support NKX2-1 as a lineage-specific tumor suppressor gene in lung carcinogenesis. PMID- 26829313 TI - The impacts of simultaneous disease intervention decisions on epidemic outcomes. AB - Mathematical models of the interplay between disease dynamics and human behavioural dynamics can improve our understanding of how diseases spread when individuals adapt their behaviour in response to an epidemic. Accounting for behavioural mechanisms that determine uptake of infectious disease interventions such as vaccination and non-pharmaceutical interventions (NPIs) can significantly alter predicted health outcomes in a population. However, most previous approaches that model interactions between human behaviour and disease dynamics have modelled behaviour of these two interventions separately. Here, we develop and analyze an agent based network model to gain insights into how behaviour toward both interventions interact adaptively with disease dynamics (and therefore, indirectly, with one another) during the course of a single epidemic where an SIRV infection spreads through a contact network. In the model, individuals decide to become vaccinated and/or practice NPIs based on perceived infection prevalence (locally or globally) and on what other individuals in the network are doing. We find that introducing adaptive NPI behaviour lowers vaccine uptake on account of behavioural feedbacks, and also decreases epidemic final size. When transmission rates are low, NPIs alone are as effective in reducing epidemic final size as NPIs and vaccination combined. Also, NPIs can compensate for delays in vaccine availability by hindering early disease spread, decreasing epidemic size significantly compared to the case where NPI behaviour does not adapt to mitigate early surges in infection prevalence. We also find that including adaptive NPI behaviour strongly mitigates the vaccine behavioural feedbacks that would otherwise result in higher vaccine uptake at lower vaccine efficacy as predicted by most previous models, and the same feedbacks cause epidemic final size to remain approximately constant across a broad range of values for vaccine efficacy. Finally, when individuals use local information about others' behaviour and infection prevalence, instead of population-level information, infection is controlled more efficiently through ring vaccination, and this is reflected in the time evolution of pair correlations on the network. This model shows that accounting for both adaptive NPI behaviour and adaptive vaccinating behaviour regarding social effects and infection prevalence can result in qualitatively different predictions than if only one type of adaptive behaviour is modelled. PMID- 26829314 TI - An estimator for local analysis of genome based on the minimal absent word. AB - This study presents an alternative alignment-free relative feature analysis method based on the minimal absent word, which has potential advantages over the local alignment method in local analysis. Smooth-local-analysis-curve and similarity-distribution are constructed for a fast, efficient, and visual comparison. Moreover, when the multi-sequence-comparison is needed, the local analysis-curves can illustrate some interesting zones. PMID- 26829315 TI - The "chi" of the Matter: Testing the Relationship between Paleoenvironments and Three Theropod Clades. AB - The view of spinosaurs as dinosaurs of semi-aquatic habits and strongly associated with marginal and coastal habitats are deeply rooted in both scientific and popular knowledge, but it was never statistically tested. Inspired by a previous analysis of other dinosaur clades and major paleoenvironmental categories, here we present our own statistical evaluation of the association between coastal and terrestrial paleoenvironments and spinosaurids, along with other two theropod taxa: abelisaurids and carcharodontosaurids. We also included a taphonomic perspective and classified the occurrences in categories related to potential biases in order to better address our interpretations. Our main results can be summarized as follows: 1) the taxon with the largest amount of statistical evidence showing it positively associated to coastal paleoenvironments is Spinosauridae; 2) abelisaurids and carcharodontosaurids had more statistical evidence showing them positively associated with terrestrial paleoenvironments; 3) it is likely that spinosaurids also occupied spatially inland areas in a way somehow comparable at least to carcharodontosaurids; 4) abelisaurids may have been more common than the other two taxa in inland habitats. PMID- 26829316 TI - A plant-wide energy model for wastewater treatment plants: application to anaerobic membrane bioreactor technology. AB - The aim of this study is to propose a detailed and comprehensive plant-wide model for assessing the energy demand of different wastewater treatment systems (beyond the traditional activated sludge) in both steady- and unsteady-state conditions. The proposed model makes it possible to calculate power and heat requirements (W and Q, respectively), and to recover both power and heat from methane and hydrogen capture. In order to account for the effect of biological processes on heat requirements, the model has been coupled to the extended version of the BNRM2 plant-wide mathematical model, which is implemented in DESSAS simulation software. Two case studies have been evaluated to assess the model's performance: (1) modelling the energy demand of two urban wastewater treatment plants based on conventional activated sludge and submerged anaerobic membrane bioreactor (AnMBR) technologies in steady-state conditions and (2) modelling the dynamics of reactor temperature and heat requirements in an AnMBR plant in unsteady-state conditions. The results indicate that the proposed model can be used to assess the energy performance of different wastewater treatment processes and would thus be useful, for example, WWTP design or upgrading or the development of new control strategies for energy savings. PMID- 26829312 TI - Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes? PMID- 26829317 TI - A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice. AB - Many genetic liver diseases in newborns cause repeated, often lethal, metabolic crises. Gene therapy using nonintegrating viruses such as adeno-associated virus (AAV) is not optimal in this setting because the nonintegrating genome is lost as developing hepatocytes proliferate. We reasoned that newborn liver may be an ideal setting for AAV-mediated gene correction using CRISPR-Cas9. Here we intravenously infuse two AAVs, one expressing Cas9 and the other expressing a guide RNA and the donor DNA, into newborn mice with a partial deficiency in the urea cycle disorder enzyme, ornithine transcarbamylase (OTC). This resulted in reversion of the mutation in 10% (6.7-20.1%) of hepatocytes and increased survival in mice challenged with a high-protein diet, which exacerbates disease. Gene correction in adult OTC-deficient mice was lower and accompanied by larger deletions that ablated residual expression from the endogenous OTC gene, leading to diminished protein tolerance and lethal hyperammonemia on a chow diet. PMID- 26829318 TI - Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo. AB - The combination of Cas9, guide RNA and repair template DNA can induce precise gene editing and the correction of genetic diseases in adult mammals. However, clinical implementation of this technology requires safe and effective delivery of all of these components into the nuclei of the target tissue. Here, we combine lipid nanoparticle-mediated delivery of Cas9 mRNA with adeno-associated viruses encoding a sgRNA and a repair template to induce repair of a disease gene in adult animals. We applied our delivery strategy to a mouse model of human hereditary tyrosinemia and show that the treatment generated fumarylacetoacetate hydrolase (Fah)-positive hepatocytes by correcting the causative Fah-splicing mutation. Treatment rescued disease symptoms such as weight loss and liver damage. The efficiency of correction was >6% of hepatocytes after a single application, suggesting potential utility of Cas9-based therapeutic genome editing for a range of diseases. PMID- 26829321 TI - Solving the Border Control Problem: Evidence of Enhanced Face Matching in Individuals with Extraordinary Face Recognition Skills. AB - Photographic identity documents (IDs) are commonly used despite clear evidence that unfamiliar face matching is a difficult and error-prone task. The current study set out to examine the performance of seven individuals with extraordinary face recognition memory, so called "super recognisers" (SRs), on two face matching tasks resembling border control identity checks. In Experiment 1, the SRs as a group outperformed control participants on the "Glasgow Face Matching Test", and some case-by-case comparisons also reached significance. In Experiment 2, a perceptually difficult face matching task was used: the "Models Face Matching Test". Once again, SRs outperformed controls both on group and mostly in case-by-case analyses. These findings suggest that SRs are considerably better at face matching than typical perceivers, and would make proficient personnel for border control agencies. PMID- 26829320 TI - Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain. AB - Recombinant adeno-associated viruses (rAAVs) are commonly used vehicles for in vivo gene transfer. However, the tropism repertoire of naturally occurring AAVs is limited, prompting a search for novel AAV capsids with desired characteristics. Here we describe a capsid selection method, called Cre recombination-based AAV targeted evolution (CREATE), that enables the development of AAV capsids that more efficiently transduce defined Cre-expressing cell populations in vivo. We use CREATE to generate AAV variants that efficiently and widely transduce the adult mouse central nervous system (CNS) after intravenous injection. One variant, AAV-PHP.B, transfers genes throughout the CNS with an efficiency that is at least 40-fold greater than that of the current standard, AAV9 (refs. 14,15,16,17), and transduces the majority of astrocytes and neurons across multiple CNS regions. In vitro, it transduces human neurons and astrocytes more efficiently than does AAV9, demonstrating the potential of CREATE to produce customized AAV vectors for biomedical applications. PMID- 26829323 TI - Erratum. PMID- 26829322 TI - Impact of Alzheimer's Disease in Nine Asian Countries. AB - BACKGROUND: Asia will soon have the majority of demented patients in the world. OBJECTIVE: To assess dementia using a uniform data system to update the current status of dementia in Asia. METHODS: A uniformed data set was administered in Taiwan, China, Hong Kong, Korea, Japan, Philippines, Thailand, Singapore, and Indonesia to gather data with regard to Alzheimer's disease (AD) and its related issues for these countries. RESULTS: In total, 2,370 AD patients and their caregivers were recruited from 2011 to 2014. The demographic characteristics of these patients and the relationships between patients and caregivers were different among individuals in these countries (p < 0.001). Of note, the family history for having dementia was 8.2% for females in contrast to 3.2% for males. CONCLUSION: Our study highlighted the differences in dementia assessment and care in developing versus developed countries. Greater effort with regard to studying dementia, especially in developing countries, is necessary. PMID- 26829319 TI - Haplotyping germline and cancer genomes with high-throughput linked-read sequencing. AB - Haplotyping of human chromosomes is a prerequisite for cataloguing the full repertoire of genetic variation. We present a microfluidics-based, linked-read sequencing technology that can phase and haplotype germline and cancer genomes using nanograms of input DNA. This high-throughput platform prepares barcoded libraries for short-read sequencing and computationally reconstructs long-range haplotype and structural variant information. We generate haplotype blocks in a nuclear trio that are concordant with expected inheritance patterns and phase a set of structural variants. We also resolve the structure of the EML4-ALK gene fusion in the NCI-H2228 cancer cell line using phased exome sequencing. Finally, we assign genetic aberrations to specific megabase-scale haplotypes generated from whole-genome sequencing of a primary colorectal adenocarcinoma. This approach resolves haplotype information using up to 100 times less genomic DNA than some methods and enables the accurate detection of structural variants. PMID- 26829324 TI - Rhinitis, Ocular, Throat and Dermal Symptoms, Headache and Tiredness among Students in Schools from Johor Bahru, Malaysia: Associations with Fungal DNA and Mycotoxins in Classroom Dust. AB - There are few studies on rhinitis and sick building syndrome (SBS) among students in tropical countries. We studied associations between levels of five fungal DNA sequences, two mycotoxins (sterigmatocystin and verrucarol) and cat allergen (Fel d 1) levels in schools and rhinitis and other weekly SBS symptoms in the students. Fungal DNA was measured by quantitative PCR and cat allergen by ELISA. Pupils (N = 462) from eight randomly selected schools in Johor Bahru, Malaysia participated (96%). Dust samples were collected by cotton swabs and Petri dishes exposed for one week. None of the schools had a mechanical ventilation system, but all classrooms had openable windows that were kept open during lectures and indoor CO2 levels were low (mean 492 ppm; range 380-690 ppm). Weekly nasal symptoms (rhinitis) (18.8%), ocular (11.6%), throat (11.1%), dermal symptoms, headache (20.6%) and tiredness (22.1%) were common. Total fungal DNA in swab samples was associated with rhinitis (p = 0.02), ocular symptoms (p = 0.009) and tiredness (p = 0.001). There were positive associations between Aspergillus versicolor DNA in Petri dish samples, ocular symptoms (p = 0.02) and tiredness (p = 0.001). The level of the mycotoxin verrucarol (produced by Stachybotrys chartarum) in swab samples was positively associated with tiredness (p = 0.04). Streptomyces DNA in swab samples (p = 0.03) and Petri dish samples (p = 0.03) were negatively associated with tiredness. In conclusion, total fungal contamination, measured as total fungal DNA) in the classrooms, Aspergillus versicolor and verrucarol can be risk factors for rhinitis and SBS symptoms among students in the tropical country Malaysia. PMID- 26829326 TI - Maintaining the continuity of HIV-care records for patients transferring care between centers: challenges, workloads, needs and risks. AB - With improved life expectancy, the medical records of HIV-infected patients are likely to be transferred repeatedly between HIV caregivers. The challenges, and risk for introducing medical error from incomplete record transfers are poorly understood. We measured number of requests for record transfer, the workload incurred, and explore, using genotypic antiretroviral resistance testing results (GART), the potential risk of incomplete records. Using retrospective database and chart review, we examined all patients followed at the Southern Alberta Clinic between 1 January 2004 and 1 January 2015, and determined how many patients transferred care into and out our program, the associated requests and the workload for record transfer. Using a complete record of all GART tests, the potential importance of absent historic records in current treatment decisions was analyzed. The annual churn rate was 22 +/- 3.4%. We received requests for only 70% of patient records who had left our care. Median time for receipt of incoming medical records was 28 days; average clerical time for processing data was 2 hours/record. Of all GART results, 25% exhibited resistance. Of 111 patients with potentially misleading GART results (i.e., documented historical resistance not visible on more recent GART), 34 (30.6%) had moved in from elsewhere. Rigorous maintenance of the continuity of the HIV record is not universally practiced. Resources, costs and logistic challenges as well as a lack of appreciation of risks clearly shown by GART testing, may be relevant barriers. Addressing such issues is pressing as aging and transfers of care are increasingly common. PMID- 26829325 TI - Cerebral Apolipoprotein-D Is Hypoglycosylated Compared to Peripheral Tissues and Is Variably Expressed in Mouse and Human Brain Regions. AB - Recent studies have shown that cerebral apoD levels increase with age and in Alzheimer's disease (AD). In addition, loss of cerebral apoD in the mouse increases sensitivity to lipid peroxidation and accelerates AD pathology. Very little data are available, however, regarding the expression of apoD protein levels in different brain regions. This is important as both brain lipid peroxidation and neurodegeneration occur in a region-specific manner. Here we addressed this using western blotting of seven different regions (olfactory bulb, hippocampus, frontal cortex, striatum, cerebellum, thalamus and brain stem) of the mouse brain. Our data indicate that compared to most brain regions, the hippocampus is deficient in apoD. In comparison to other major organs and tissues (liver, spleen, kidney, adrenal gland, heart and skeletal muscle), brain apoD was approximately 10-fold higher (corrected for total protein levels). Our analysis also revealed that brain apoD was present at a lower apparent molecular weight than tissue and plasma apoD. Utilising peptide N-glycosidase-F and neuraminidase to remove N-glycans and sialic acids, respectively, we found that N-glycan composition (but not sialylation alone) were responsible for this reduction in molecular weight. We extended the studies to an analysis of human brain regions (hippocampus, frontal cortex, temporal cortex and cerebellum) where we found that the hippocampus had the lowest levels of apoD. We also confirmed that human brain apoD was present at a lower molecular weight than in plasma. In conclusion, we demonstrate apoD protein levels are variable across different brain regions, that apoD levels are much higher in the brain compared to other tissues and organs, and that cerebral apoD has a lower molecular weight than peripheral apoD; a phenomenon that is due to the N-glycan content of the protein. PMID- 26829328 TI - Correction: Structural and Functional Similarity of Amphibian Constitutive Androstane Receptor with Mammalian Pregnane X Receptor. PMID- 26829327 TI - Assessment of the Geographic Distribution of Ornithodoros turicata (Argasidae): Climate Variation and Host Diversity. AB - BACKGROUND: Ornithodoros turicata is a veterinary and medically important argasid tick that is recognized as a vector of the relapsing fever spirochete Borrelia turicatae and African swine fever virus. Historic collections of O. turicata have been recorded from Latin America to the southern United States. However, the geographic distribution of this vector is poorly understood in relation to environmental variables, their hosts, and consequently the pathogens they transmit. METHODOLOGY: Localities of O. turicata were generated by performing literature searches, evaluating records from the United States National Tick Collection and the Symbiota Collections of Arthropods Network, and by conducting field studies. Maximum entropy species distribution modeling (Maxent) was used to predict the current distribution of O. turicata. Vertebrate host diversity and GIS analyses of their distributions were used to ascertain the area of shared occupancy of both the hosts and vector. CONCLUSIONS AND SIGNIFICANCE: Our results predicted previously unrecognized regions of the United States with habitat that may maintain O. turicata and could guide future surveillance efforts for a tick capable of transmitting high-consequence pathogens to human and animal populations. PMID- 26829329 TI - Response to "Comment on 'Exposure to Road Traffic Noise and Behavioral Problems in 7-Year-Old Children: A Cohort Study'". PMID- 26829330 TI - Trajectory Pathways for Depressive Symptoms and Their Associated Factors in a Chinese Primary Care Cohort by Growth Mixture Modelling. AB - BACKGROUND: The naturalistic course for patients suffering from depressive disorders can be quite varied. Whilst some remit with little or no intervention, others may suffer a more prolonged course of symptoms. The aim of this study was to identify trajectory patterns for depressive symptoms in a Chinese primary care cohort and their associated factors. METHODS AND RESULTS: A 12-month cohort study was conducted. Patients recruited from 59 primary care clinics across Hong Kong were screened for depressive symptoms using the Centre for Epidemiologic Studies Depression Scale (CES-D) and monitored over 12 months using the Patient Health Questionnaire-9 items (PHQ-9) administered at 12, 26 and 52 weeks. 721 subjects were included for growth mixture modelling analysis. Using Akaike Information Criterion, Bayesian Information Criterion, Entropy and Lo-Mendell-Rubin adjusted likelihood ratio test, a seven-class trajectory path model was identified. Over 12 months, three trajectory groups showed improvement in depressive symptoms, three remained static, whilst one deteriorated. A mild severity of depressive symptoms with gradual improvement was the most prevalent trajectory identified. Multivariate, multinomial regression analysis was used to identify factors associated with each trajectory. Risk factors associated with chronicity included: female gender; not married; not in active employment; presence of multiple chronic disease co-morbidities; poor self-rated general health; and infrequent health service use. CONCLUSIONS: Whilst many primary care patients may initially present with a similar severity of depressive symptoms, their course over 12 months can be quite heterogeneous. Although most primary care patients improve naturalistically over 12 months, many do not remit and it is important for doctors to be able to identify those who are at risk of chronicity. Regular follow-up and greater treatment attention is recommended for patients at risk of chronicity. PMID- 26829332 TI - Determination of phenobarbital in hair matrix by liquid phase microextraction (LPME) and gas chromatography-mass spectrometry (GC-MS). AB - A method for identification and quantification of phenobarbital in hair samples by liquid phase microextraction (LPME) and gas chromatography-mass spectrometry (GC-MS) has been presented. Drug-free hair specimens were collected and separated in 50mg aliquots. Each aliquot was washed with 2.0mL of dichloromethane for 15min at 37 degrees C. Standards and deuterated internal standards for calibration and quality control samples were added to the washed hair aliquot and the sample was submitted to complete digestion with sodium hydroxide (NaOH) 1.0mol/L for 15min at 70 degrees C. The dissolved sample was submitted to LPME. After extraction, the residue was derivatized with tetramethylammonium hydroxide (TMAH) and analyzed by GC-MS. The limit of detection (LOD) was 0.1ng/mg and the limit of quantification (LOQ) was 0.25ng/mg. The calibration curve was linear over a concentration range of 0.25ng/mg to 10ng/mg (r(2)>0.99). The intra- and inter assay precisions, given by RSD, were less than 6% for phenobarbital. Fortified samples of secobarbital and pentobarbital were also submitted to the validated method. The method was successfully applied to hair samples collected from three volunteers who reported regular use of phenobarbital (clinical treatment). The concentrations found were 9.5, 15.1 and 16.3ng/mg of phenobarbital. To contemplate the concentrations found, dilution integrity tests were also validated. The LPME and GC-MS method showed to be suitable for the detection of phenobarbital in hair samples and can be promptly used for different purposes whenever required. PMID- 26829331 TI - Resveratrol analogue 4,4'-dihydroxy-trans-stilbene potently inhibits cancer invasion and metastasis. AB - We investigated the preventive effects of resveratrol analogue 4,4'-dihydroxy trans-stilbene (DHS) on cancer invasion and metastasis. Two different in vivo approaches of mouse and zebrafish lung cancer invasion models were employed in our study. The in vitro results showed that DHS displays potent inhibition on anchorage-dependent or -independent cell growth of LLC cells, leading to impairment of the cell cycle progression with reduction of cell numbers arresting at the G1 phase, an evident accumulation of pre-G1 events correlated with apoptotic behaviour. In addition, DHS induces a marked inhibition of LLC cell migration and matrigel invasion. In a murine lung cancer model, tumour volume, cell proliferation, and tumour angiogenesis were significantly inhibited by DHS. Importantly, liver metastatic lesions were significantly reduced in DHS-treated mice. Similarly, DHS significantly inhibits lung cancer cell dissemination, invasion and metastasis in a zebrafish tumour model. These findings demonstrate that DHS could potentially be developed as a novel therapeutic agent for treatment of cancer and metastasis. PMID- 26829333 TI - Determination of glyphosate and its metabolite in emergency room in Korea. AB - The number of glyphosate intoxication cases has been increased after the regulation of paraquat. Unfortunately, there are no reports on the potential concentration of glyphosate for those acute intoxicated patients admitted to emergency rooms and the correlation between the concentration of glyphosate and clinical symptoms in Korea up to our knowledge. As a nonselective herbicide, analysis of glyphosate requires derivatization because of its amphoteric and strongly polar nature. In order to develop a method to determine the concentration of glyphosate and its metabolite, aminomethylphosphonic acid (AMPA) in blood samples without derivatization, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was utilized with a hydrophilic interaction chromatography (HILIC) column. The validation of this method showed that the limits of detection (LODs) and limits of quantitation (LOQs) for glyphosate and AMPA were 50 and 100ng/mL, respectively. In addition, matrix effect, recovery rate, and accuracy and precision in intra and inter-day were evaluated during the validation study of this method. Blood samples acquired from five glyphosate intoxicated patients were analyzed to investigate the correlation between the concentration of glyphosate and clinical symptoms. These patients were previously admitted to the emergency room at a University Hospital in Korea after glyphosate was self-administered in suicide attempts or by accident. As results of blood sample study, the concentration of glyphosate and AMPA were found in the range of 1.0-171.1 and 0.2-2.6MUg/mL, respectively. The concentration ratio of glyphosate to AMPA was 55-71. According to the clinical reports for those patients, they were in the age between 47 and 82 years old and administered about 50-400mL. The blood samples were collected within 2-5h after administration of glyphosate. Among the intoxicated patients, the most common clinical symptom was metabolic acidosis, identified in four patients. The comparison between the concentration of glyphosate and administered dosage did not show the correlation, which suggests further investigation on the effects of surfactants in glyphosate from different vendors. PMID- 26829334 TI - Amphetamines and cannabinoids testing in hair: Evaluation of results from a two year period. AB - This paper presents an overview of a set of amphetamines and cannabinoids tests performed on head hair samples from the Medico-Legal sector at the Madrid Department of the Spanish National Institute of Toxicology and Forensic Sciences during the years 2013 and 2014. The hair samples were tested for five stimulant phenylalkylamine derivatives -amphetamine (AP), methamphetamine (MA), 3,4 methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxy-amphetamine (MDA), and 3,4-methylenedioxy-N-ethylamphetamine (MDEA)- and/or two cannabinoids-Delta(9) tetrahydrocannabinol (THC) and cannabinol (CBN)- by gas chromatography equipped with mass spectrometry detection in selected-ion monitoring mode, applying a method accredited to ISO/IEC 17025 standards. The test results were interpreted according to the confirmation cut-offs proposed by the Society of Hair Testing (SoHT) to identify chronic drug use. The ratios of positive results were studied in relation to gender, age, hair colour, dyeing and length of the tested samples to assess the independence from these variables or the association with them. Low, medium and high ranges of concentration were also estimated for each drug. 21.94% of the 2954 hair samples tested for phenylalkylamine derivatives were positive for one or more substances. 16.38% of the samples were positive for AP, 12.09% for MDMA and only 0.44% for MA. 6.60% of the tested samples were positive for AP/MDMA combination. A total of 3178 samples were tested for cannabinoids, resulting in 53.40% positive for THC and CBN. Simultaneous tests for phenylalkylamine derivatives and cannabinoids were performed in 2931 of the samples; 14.94% of them were positive for THC, CBN, and one or more amphetamines. According to the results from the statistical analysis, the use of THC and MDMA vary with age and gender among the Medico-Legal sector in an extended area of Spain, while the use of AP appears to be independent of these variables. On the other hand, the results of THC in hair could be influenced by the length of the tested segment; therefore, a consensus regarding the hair length between 3.0 and 5.5cm for THC testing should be reached. PMID- 26829335 TI - A study to model the post-mortem stability of 4-MMC, MDMA and BZP in putrefying remains. AB - There is currently limited data available on the stabilities of the three stimulants 4-methylmethcathinone (4-MMC), 3,4-methylenedioxymethamphetamine (MDMA) and N-benzylpiperazine (BZP) in a putrefying matrix. A Gas Chromatography Mass Spectrometry (GC-MS) method to determine the concentration of the three drugs in putrefying porcine liver over a three month period was developed and validated. Both 4-MMC and BZP were found to be unstable, becoming undetectable and having an average recovery of 52% respectively after one month at ambient room temperature (20 degrees C). MDMA was found to be moderately stable, with an average recovery of 74% after three months at room temperature. This study indicated that the putrefaction process could have a significant impact on concentrations of 4-MMC and BZP in post-mortem cases involving putrefied remains. PMID- 26829336 TI - Formation and inhibition of ethyl glucuronide and ethyl sulfate. AB - Ethyl glucuronide (EtG) und ethyl sulfate (EtS) are widely accepted biomarkers in forensic and clinical settings. Even though, levels of EtG and EtS in blood and urine increase with increasing doses of alcohol, a high inter-individual variability in their production has been noticed. Therefore, we investigated the influence of dietary plant phenols on the formation of EtG and EtS and tentatively estimated the magnitude of in vivo inhibitory interactions from our in vitro results. To address these issues, formation of EtS and EtG was investigated using recombinant glucuronosyl- and sulfotransferases as well as human liver microsomes and liver cytosol. After respective kinetics had been established, inhibition experiments using quercetin, kaempferol and resveratrol were performed. These polyphenols are subject to extensive glucuronidation and/or sulfonation. EtG and EtS were determined by LC-MS/MS following solid phase extraction for EtG due to severe matrix effects and by direct injection for EtS. All enzymes investigated were involved in the conjugation of ethanol. Maximal EtG and EtS formation rates were observed with HLM and SULT1A1, respectively. All kinetics could best be described by Michaelis-Menten kinetics. Resveratrol was a competitive inhibitor of UGT1A1, UGT1A9 and HLM; quercetin and kaempferol were inhibitors of all transferases under investigation except UGT2B15. Findings for quercetin with regard to UGT2B7 and SULT2A1 and for kaempferol with regard to SULT1E1 and SULT2A1 suggested a mechanism based inhibition. Competitive inhibition of the glucuronidation and sulfonation of ethanol was estimated as weak to negligible and as moderate to weak, respectively. Beside the known polymorphisms of the transferases involved in EtG and EtS formation, prediction of the inhibitory potential indicates that polyphenols may contribute to the variable formation rate of EtG and EtS. PMID- 26829337 TI - Interference of anesthetics in blood alcohol analysis by HS-GC-FID: A case report. AB - One of the techniques most widely used in ethanol analysis in forensic laboratories is undoubtedly the headspace gas chromatography with flame ionization detection (HS-GC-FID) since the determination of this substance is carried out directly, without the need for additional purification procedures, which leads to increased productivity. This is a very important factor due to the high number of alcohol analysis requested to these laboratories. The presence of other volatile substances can cause a problem given the fact that they can be interferents in ethanol analysis by HS-GC-FID, which can have legal consequences related with driving under the influence of alcohol. The authors report a case of a routine analysis by HS-GC-FID for the determination of ethanol of a driver who has suffered an accident in which the use of two chromatographic columns with different polarities was essential to obtain an unequivocally identification of this substance in presence of an interfering volatile anesthetic administered in the hospital. The method was validated according to international recommendations before being introduced into routine laboratory in terms of selectivity, limits of detection (LOD), limits of quantification (LOQ), linearity, repeatability, intermediate precision, accuracy, robustness and carryover. PMID- 26829338 TI - Seven fatalities associated with ethylphenidate. AB - Ethylphenidate is a stimulant novel psychoactive substance that is an analogue of the prescription drug methylphenidate (Ritalin((r))). Methylphenidate is used commonly for the treatment of attention deficit hyperactivity disorder. Due to its stimulant effects ethylphenidate is being abused. There is a single case report of a death associated with ethylphenidate in Germany, and a case series of 19 deaths in the East of Scotland, but otherwise, the contribution of ethylphenidate to death is poorly documented. We report the analytical results of 7 cases (between February 2013 and January 2015) in which ethylphenidate was detected and quantitated with a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The individuals (all male) ranged in age from 23 to 49 years (median 25 years). The concentration of ethylphenidate in the cases ranged from 0.026mg/L to 2.18mg/L in unpreserved post-mortem femoral blood. Only one case had ethylphenidate present as a sole drug. All other cases had at least 2 other drug classes present (benzodiazepines, heroin, methadone antipsychotics, other new psychoactive compounds). Ethylphenidate toxicity was the sole contribution to the cause of death in one case. Hanging was the cause of death in 2 cases, with the other 4 cases being reported as having occurred due to mixed drug toxicity. These data will further help with the interpretation of post mortem ethylphenidate levels. PMID- 26829339 TI - Orthogonally Substituted Benzimidazole-Carbazole Benzene As Universal Hosts for Phosphorescent Organic Light-Emitting Diodes. AB - The novel ambipolar hosts of o-CbzBz and o-DiCbzBz contain carbazole and benzimidazole through an ortho-connection. The orthogonal conformations cause the triplet state to be confined at the carbazole units to secure efficient energy transfer. The phosphorescent organic light-emitting diodes (PhOLEDs) show a high current efficiency, power efficiency, and low efficiency roll-off. o-DiCbzBz can be used as a host for sky-blue, green, and orange-red PhOLEDs, giving 57.5, 78.4, and 60.3 cd/A, respectively. PMID- 26829340 TI - Analysis of protamine peptides in insulin pharmaceutical formulations by capillary electrophoresis. AB - Protamines are a group of highly basic peptides that are sometimes added to insulin formulations to prolong the pharmacological action. In this study, different methods were investigated to identify protamine in insulin formulations. Capillary electrophoresis in aqueous and non-aqueous media was tested to separate these peptides with very close amino acid sequences. Different buffers (phosphate or formate, both acidified) and various additives (principally negatively charged and neutral surfactants) were investigated to optimize peptide separation. Finally, a micellar electrokinetic capillary chromatography method using a capillary of 120 cm effective length and an aqueous background electrolyte made up of 100 mM phosphate buffer (pH 2) and 50 mM Thesit(r) gave the best results, providing the separation of the four major protamine peptides within 25 min. PMID- 26829341 TI - Tracking the Spatial Fate of PCDD/F Emissions from a Cement Plant by Using Lichens as Environmental Biomonitors. AB - In an area with multiple sources of air pollution, it is difficult to evaluate the spatial impact of a minor source. Here, we describe the use of lichens to track minor sources of air pollution. The method was tested by transplanting lichens from a background area to the vicinity of a cement manufacturing plant that uses alternative fuel and is located in a Natural Park in an area surrounded by other important sources of pollution. After 7 months of exposure, the lichens were collected and analyzed for 17 PCDD/F congeners. The PCDD/F profiles of the exposed lichens were dominated by TCDF (50%) and OCDD (38%), which matched the profile of the emissions from the cement plant. The similarity in the profiles was greatest for lichens located northeast of the plant (i.e., in the direction of the prevailing winds during the study period), allowing us to evaluate the spatial impact of this source. The best match was found for sites located on the tops of mountains whose slopes faced the cement plant. Some of the sites with highest influence of the cement plant were the ones with the highest concentrations, whereas others were not. Thus, our newly developed lichen-based method provides a tool for tracking the spatial fate of industrially emitted PCDD/Fs regardless of their concentrations. The results showed that the method can be used to validate deposition models for PCDD/F industrial emissions in sites with several sources and characterized by complex orography. PMID- 26829342 TI - Does Pelvic Organ Prolapse Quantification Examination D Point Predict Uterosacral Ligament Suspension Outcomes? AB - OBJECTIVES: The best predictors for postoperative anatomic apical success after transvaginal uterosacral ligament suspension remain unknown. The aim of this study was to determine if there is a correlation between the preoperative D point and anatomic outcomes for apical prolapse after 1 year. METHODS: This retrospective cohort study included subjects undergoing transvaginal uterosacral ligament suspension from 2008 through 2013 who had at least 1 year follow-up. Demographic information, preoperative and postoperative Pelvic Organ Prolapse Quantification (POPQ) examination measurements, need for retreatment or repeat surgery, and assessment of pelvic floor symptoms were reviewed. Postoperative apical success was defined as C point descent no more than one third into the vaginal canal. RESULTS: One hundred twenty-five women met inclusion criteria and had follow-up at 1 year or more. Concomitant procedures included anterior/posterior repair and midurethral sling. Mean follow-up time was 22.8 months (range, 12-63 months). At last follow-up, 96% met criteria for apical success. A more negative preoperative D point was significantly related to improved postoperative apical support, with each 1-cm descent in preoperative D point resulting in a postoperative C point that was 0.21 cm lower (P = 0.0005). Based on the receiver operating characteristic curve, a "cutoff" D point value of -4.25 (sensitivity, 0.8; specificity, 0.65) was determined to be a predictor of postoperative apical success at 1 year or more. CONCLUSIONS: The preoperative D point correlates with postoperative apical support, and a clinically meaningful relationship exists between the preoperative D point and anatomic apical success. PMID- 26829343 TI - Impact of Pelvic Floor Physical Therapy on Quality of Life and Function After Obstetric Anal Sphincter Injury: A Randomized Controlled Trial. AB - OBJECTIVES: There is no standard of care for women sustaining an obstetric anal sphincter injury (OASIS). We sought to determine whether pelvic floor physical therapy (PFPT) would improve the quality of life and function in women 12 weeks after OASIS. METHODS: This institutional review board-approved randomized trial enrolled primiparous women 2 weeks after delivery complicated by OASIS. After informed consent, all subjects underwent vaginal electromyography and anorectal manometry and completed validated questionnaires; measures were repeated for all subjects at 12 weeks after delivery. The intervention arm completed 4 PFPT sessions. The primary outcome was a change in the Fecal Incontinence Quality of Life. RESULTS: Three hundred four women were screened; 250 were excluded, and 54 were randomized. After four were lost to follow-up, analysis included 27 in the intervention arm and 23 in the control arm. Overall, mean age was 29.8 +/- 4.7 years, and there were no demographic differences between groups.Fecal Incontinence Quality of Life domain scores showed improvement for both groups from baseline to 12 weeks for coping (P = 0.006) and depression (P = 0.009); however, there was no difference in domain scores between groups. For the secondary outcome of anorectal manometry, squeezing pressure improved for all subjects (P = 0.035) from baseline to 12 weeks. Vaginal EMG strength (microvolts) increased for all subjects in measures of rest average (P < 0.000), rapid peak (P = 0.006), and work average (P < 0.000), with no difference based on therapeutic arm. CONCLUSIONS: All women showed improvements in quality of life and function at 12 weeks after delivery, regardless of treatment allocation. Further study is needed to determine whether PFPT provides a significant benefit to women having OASIS. PMID- 26829344 TI - The Pelvic Floor Disorders Registry: Purpose and Development. AB - Pelvic organ prolapse (POP) is a common problem that negatively impacts women's quality of life. A variety of surgeries exist for POP treatment, including procedures performed with and without mesh augmentation. The growing use of mesh in prolapse surgeries in the 2000s was associated with increasing reports of complications, resulting in Food and Drug Administration (FDA) Safety Notifications, and in 2012, the FDA ordered transvaginal mesh manufacturers to conduct prospective studies to evaluate longer-term outcomes. These requirements provided incentives and an environment conducive to collaboration. American Urogynecologic Society leaders collaborated with device manufacturers, the FDA, and other professional organizations to establish the Pelvic Floor Disorders Registry (PFDR), a collection of interrelated registries, which could meet manufacturers' needs but also allow surgeons to track individual and aggregate outcomes for quality improvement. The PFDR was developed and launched by American Urogynecologic Society with objectives of (1) collecting, storing, and analyzing clinical data related to POP treatment; (2) establishing common data elements and quality metrics; and (3) providing a framework for external stakeholders to conduct POP research. The PFDR includes industry-sponsored studies, as well as 2 options for volunteer registry participation, the PFDR-Quality Improvement and PFDR-Research. The PFDR promotes quality improvement and national benchmarking and will provide real-world comparative safety and effectiveness data for prolapse surgeries. The PFDR can serve as a model for collaboration between medical practitioners, researchers, industry, and federal agencies and may allow progress toward our similar goal of high-quality surgical care of women with prolapse. PMID- 26829345 TI - A Novel Cystometric Model of Pelvic Floor Dysfunction After Rabbit Pelvic Floor Noxious Electrical Stimulation. AB - OBJECTIVES: Although a relationship between pelvic floor dysfunction and lower urinary tract symptoms is described in the literature, the mechanism and pathways need further characterization. We developed an animal model of pelvic floor dysfunction after noxious stimulation of the pubococcygeus (PC) muscle. METHODS: Fifteen female adult rabbits were evaluated with cystometry (CMG) and electromyography (EMG) recordings from the PC muscle. Cystometry/EMG was performed before and after treatment animal (n = 11) received noxious pelvic floor electrical stimulation through the PC EMG electrode, and controls (n = 4) underwent sham needle placement. Two animals underwent S3 dorsal rhizotomy to demonstrate that the observed results required afferent innervation. RESULTS: Voiding changes were demonstrated in 9 of 11 rabbits after stimulation. Most of the rabbits (7/9) exhibited a prolonged-dysfunctional voiding pattern with larger capacity (mean, 17 mL [SEM, +/-8 mL]), longer intercontractile interval (227% [SEM, +/-76%]) and duration (163% [SEM, +/-20%]), and increased postvoid residual (24 mL [SEM, +/-6 mL]). The remaining dysfunctional rabbits (2/9) exhibited an overactive-dysfunctional voiding pattern with lower capacity (-26 mL [SEM, +/-6 mL]), shortened intercontractile interval (16% [SEM, +/-9%]) and duration (56% [SEM, +/-30%]), and decreased postvoid residual (-27 mL [SEM, +/-6 mL]). Nonresponder rabbits (2/11) were relatively unchanged in their micturition cycles after stimulation. Rhizotomy animals were acontractile and filled until overflow incontinence occurred. CONCLUSIONS: Using noxious electrical stimulation of the pelvic musculature, we were able to produce an animal model of pelvic floor dysfunction in most rabbits as hallmarked by a larger bladder capacity, an increased intercontractile interval, and prolonged contraction duration. PMID- 26829346 TI - Defining Patient Knowledge and Perceptions of Vaginal Pessaries for Prolapse and Incontinence. AB - OBJECTIVE: The aim of this study was to define patient knowledge and perceptions of pessaries to identify barriers to care and inform physician counseling efforts. METHODS: An anonymous survey was distributed to a convenience sample of new patients presenting to the urogynecology clinic at a single academic medical center. Data analysis was performed using standard bivariate and logistic regression models. RESULTS: A total of 254 women completed the survey. Only half of respondents indicated prior knowledge of pessaries. The most common source of prior knowledge was a physician or other health care provider (100/130, 76.9%); comparatively few women had heard about pessaries from any other source. Patients presented with a negative view of pessaries, 3.6 +/- 2.2 on a 0- to 10-point Likert scale, and only a third of patients indicated they would consider pessary use as a treatment option for their condition. On multivariable logistic regression, having previously seen a gynecologist (P = 0.03) and a lower level of education (P = 0.05) independently predicted aversion to pessary use. CONCLUSIONS: Only half of patients presenting to a referral-based practice had previous knowledge of vaginal pessaries. Few patients had heard about pessaries from any source other than a physician or other health care provider. Patients presented with a negative impression of pessaries and a high level of aversion to pessary use. Patients who indicated they would decline pessary use reported a lower level of education and were more likely to have previously seen a gynecologist for evaluation of their condition. These data may inform physician counseling efforts. PMID- 26829347 TI - Vaginal Expression of LOXL1 in Premenopausal and Postmenopausal Women With Pelvic Organ Prolapse. AB - OBJECTIVES: This study aimed to compare cellular expression of lysyl oxidase-like 1 (LOXL1), a key enzyme in elastin metabolism, of premenopausal women with pelvic organ prolapse (POP) compared with premenopausal controls without POP and postmenopausal women with POP. In addition, we examined whether variation of LOXL1 expression was dependent on biopsy site. METHODS: A standardized protocol was utilized to obtain vaginal biopsies from 30 women (10 premenopausal POP, 10 postmenopausal POP, and 10 premenopausal non-POP). Expression levels of messenger RNA (mRNA) and protein of LOXL1 were determined using real-time quantitative polymerase chain reactions and enzyme-linked immunosorbant assays. Analysis was performed to determine if there were differences between group or biopsy site. RESULTS: Significant differences in LOXL1 mRNA expression were found between patient groups (P = 0.0033). LOXL1 mRNA expression (relative to 18S) was upregulated in the postmenopausal POP group (54.5 +/- 14.7) compared with the premenopausal POP group (5.2 +/- 14.7, P = 0.0034) and the premenopausal non-POP group (23 +/- 18, P = 0.0359). No significant differences in LOXL1 protein expression (nanogram/milliliter per microgram total protein) were seen between groups (premenopausal POP, 3.2 * 10 +/- 6.3 * 10; postmenopausal POP, 4.3 * 10 +/ 6.3 * 10; premenopausal non-POP, 5.0 * 10 +/- 7.7 * 10; P = 0.15). No differences in mRNA expression were seen between sites (P = 0.74), but significant variation was noted in protein expression (P = 0.001). CONCLUSIONS: Premenopausal and postmenopausal women with POP exhibit differential expression of LOXL1 suggesting different pathways in the pathogenesis of POP. The role of biopsy location on LOXL1 expression requires further investigation. PMID- 26829349 TI - Ultrasound Evaluation of the Urethra and Bladder Neck Before and After Transurethral Bulking. AB - OBJECTIVES: The aims of the study were to describe ultrasound findings in women with stress urinary incontinence (SUI) after transurethral injection of Coaptite, to describe symptoms 3 months after injection, and to determine whether there was an association between degree of improvement and sonographic findings. METHODS: This is a prospective cohort study of women with SUI undergoing transurethral Coaptite injection. Subjects completed the Urinary Distress Inventory and Incontinence Severity Index preinjection and 3 months postinjection. Translabial ultrasound was performed immediately after and 3 months postinjection. Two- and three-dimensional images were captured to measure the dimensions and location of Coaptite in relation to the bladder neck as well as degree of coaptation. Change in volume of injection over time was calculated using these measurements. RESULTS: Twenty subjects were enrolled in the study. At 3 months, 45% of subjects had 90% or greater improvement, 45% had 50% to 75% improvement, and 10% had less than 30% improvement. Mean distance of Coaptite from the bladder neck at 3 months was not statistically different from the distance immediately after injection. There was a 40.9% to 45.8% mean reduction in volume at 3 months as well as a 39.5% reduction in coaptation. Degree of improvement was associated with mean change in volume over time: those with the least improvement had the greatest reduction in volume. Volume of initial injection, percent coaptation, and number of vials used to perform the injection were not associated with patient symptoms. CONCLUSIONS: In this series, 90% of patients who underwent Coaptite injection for SUI reported 50% or greater improvement. The volume of Coaptite decreased by 40% over time, and the degree of shrinkage correlated with clinical outcomes. PMID- 26829348 TI - A Randomized Controlled Trial of Patient-Controlled Valve Catheter and Indwelling Foley Catheter for Short-term Bladder Drainage. AB - OBJECTIVE: The purpose of this study was to compare catheter-related pain and quality-of-life scores between 2 catheters used after failed voiding trials following urogynecologic surgery. METHODS: Women failing an inpatient voiding trial requiring short-term catheterization after urogynecologic surgery were randomized to receive either a standard FC or a patient-controlled VC. Subjects completed a 6-item, visual analog scale-based postoperative questionnaire (POQ) and an outpatient voiding trial 3 to 7 days after surgery. Baseline demographic, surgical data, and results of the outpatient voiding trial were recorded. The primary outcome was the difference in mean score for catheter-related pain on the POQ, based on intent to treat. Secondary outcomes included between-group differences in means for individual POQ items and a calculated composite satisfaction score. The statistician was blinded to group assignment. RESULTS: Forty-nine subjects were randomized to FC (n = 24) and VC (n = 25). Two subjects, one in each group, were excluded from the primary analysis because of missing data. Mean age was 60.6 (SD, 12.5) years. Baseline characteristics were similar. Valve catheter users had a lower median catheter-related pain score (1.25 vs 2.3), but not significantly (P = 0.153). Valve catheter users had significantly lower median scores for frustration (1.2 vs 3.8; P = 0.018) and limitation on social activities (0 vs 7.6; P < 0.001). Mean composite satisfaction score was statistically significantly lower for the VC group (2.23 [SD, 1.83] vs 3.62 [SD, 1.95]; P < 0.01), suggesting greater satisfaction. CONCLUSIONS: Valve catheter and FC users report similar catheter-related pain. Valve catheter users scored better in overall satisfaction, frustration, and limitations on social activities. PMID- 26829350 TI - The Role of Chronic Mesh Infection in Delayed-Onset Vaginal Mesh Complications or Recurrent Urinary Tract Infections: Results From Explanted Mesh Cultures. AB - OBJECTIVES: Vaginal mesh complications necessitating excision are increasingly prevalent. We aim to study whether subclinical chronically infected mesh contributes to the development of delayed-onset mesh complications or recurrent urinary tract infections (UTIs). METHODS: Women undergoing mesh removal from August 2013 through May 2014 were identified by surgical code for vaginal mesh removal. Only women undergoing removal of anti-incontinence mesh were included. Exclusion criteria included any women undergoing simultaneous prolapse mesh removal. We abstracted preoperative and postoperative information from the medical record and compared mesh culture results from patients with and without mesh extrusion, de novo recurrent UTIs, and delayed-onset pain. RESULTS: One hundred seven women with only anti-incontinence mesh removed were included in the analysis. Onset of complications after mesh placement was within the first 6 months in 70 (65%) of 107 and delayed (>=6 months) in 37 (35%) of 107. A positive culture from the explanted mesh was obtained from 82 (77%) of 107 patients, and 40 (37%) of 107 were positive with potential pathogens. There were no significant differences in culture results when comparing patients with delayed-onset versus immediate pain, extrusion with no extrusion, and de novo recurrent UTIs with no infections. CONCLUSIONS: In this large cohort of patients with mesh removed for a diverse array of complications, cultures of the explanted vaginal mesh demonstrate frequent low-density bacterial colonization. We found no differences in culture results from women with delayed-onset pain versus acute pain, vaginal mesh extrusions versus no extrusions, or recurrent UTIs using standard culture methods. Chronic prosthetic infections in other areas of medicine are associated with bacterial biofilms, which are resistant to typical culture techniques. Further studies using culture-independent methods are needed to investigate the potential role of chronic bacterial infections in delayed vaginal mesh complications. PMID- 26829351 TI - The cellulose synthase companion proteins act non-redundantly with CELLULOSE SYNTHASE INTERACTING1/POM2 and CELLULOSE SYNTHASE 6. AB - Cellulose is a cell wall constituent that is essential for plant growth and development, and an important raw material for a range of industrial applications. Cellulose is synthesized at the plasma membrane by massive cellulose synthase (CesA) complexes that track along cortical microtubules in elongating cells of Arabidopsis through the activity of the protein CELLULOSE SYNTHASE INTERACTING1 (CSI1). In a recent study we identified another family of proteins that also are associated with the CesA complex and microtubules, and that we named COMPANIONS OF CELLULOSE SYNTHASE (CC). The CC proteins protect the cellulose synthesising capacity of Arabidopsis seedlings during exposure to adverse environmental conditions by enhancing microtubule dynamics. In this paper we provide cell biology and genetic evidence that the CSI1 and the CC proteins fulfil distinct functions during cellulose synthesis. We also show that the CC proteins are necessary to aid cellulose synthesis when components of the CesA complex are impaired. These data indicate that the CC proteins have a broad role in aiding cellulose synthesis during environmental changes and when core complex components are non-functional. PMID- 26829352 TI - Descending necrotizing mediastinitis: Systematic review on its treatment in the last 6 years, 75 years after its description. AB - BACKGROUND: Descending necrotizing mediastinitis is a serious infection involving the neck and the chest, in which an odontogenic, pharyngeal, or cervical infection spreads rapidly to the thoracic cavity, with a high death rate by sepsis and organic failure if not treated quickly and properly. METHODS: A systematic search in the electronic database PubMed was conducted using the keywords "mediastinitis" and "descending necrotizing mediastinitis" resulting in 2560 items, filters were activated (systematic review, meta-analysis, and clinical trial) resulting in 60 articles, from which we selected relevant articles on the topic. RESULTS: The best available evidence we could obtain was from 26 case series with evidence level III. The overall mortality in this period was 17.5%. CONCLUSION: For mediastinitis limited to the upper part of the mediastinum, transcervical drainage may be sufficient; cases that extended below the tracheal carina may require cervical and transthoracic drainage. A multidisciplinary therapeutic approach has allowed a reduction in its mortality. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2275-E2283, 2016. PMID- 26829354 TI - Education Considerations: Communication Curricula, Simulated Resuscitation, and Duty Hour Restrictions. PMID- 26829353 TI - Phosphorylation of serine residue modulates cotton Di19-1 and Di19-2 activities for responding to high salinity stress and abscisic acid signaling. AB - Di19 (drought-induced protein 19) family is a novel type of Cys2/His2 zinc-finger proteins. In this study, we demonstrated that cotton Di19-1 and Di19-2 (GhDi19-1/ 2) proteins could be phosphorylated in vitro by the calcium-dependent protein kinase (CDPK). Mutation of Ser to Ala in N-terminus of GhDi19-1/-2 led to the altered subcellular localization of the two proteins, but the constitutively activated form (Ser was mutated to Asp) of GhDi19-1/-2 still showed the nuclear localization. GhDi19-1/-2 overexpression transgenic Arabidopsis seedlings displayed the hypersensitivity to high salinity and abscisic acid (ABA). However, Ser site-mutated GhDi19-1(S116A) and GhDi19-2(S114A), and Ser and Thr double sites-mutated GhDi19-1(S/T-A/A) and GhDi19-2(S/T-A/A) transgenic Arabidopsis did not show the salt- and ABA-hypersensitive phenotypes. In contrast, overexpression of Thr site-mutated GhDi19-1(T114A) and GhDi19-2(T112A) in Arabidopsis still resulted in salt- and ABA-hypersensitivity phenotypes, like GhDi19-1/-2 transgenic lines. Overexpression of GhDi19-1/-2 and their constitutively activated forms in Atcpk11 background could recover the salt- and ABA-insensitive phenotype of the mutant. Thus, our results demonstrated that Ser phosphorylation (not Thr phosphorylation) is crucial for functionally activating GhDi19-1/-2 in response to salt stress and ABA signaling during early plant development, and GhDi19-1/-2 proteins may be downstream targets of CDPKs in ABA signal pathway. PMID- 26829356 TI - A Qualitative Study of Client-Clinician Text Exchanges in a Mobile Health Intervention for Individuals With Psychotic Disorders and Substance Use. AB - OBJECTIVE: Mobile health (mHealth) approaches have the potential to transform prevention, wellness, and illness management for people with dual diagnosis consisting of co-occurring mental illness and substance use disorders by providing timely and cost-effective interventions in clients' natural environments. However, little is known about how clients interact with mHealth interventions to manage their illness. This qualitative study explored the content of mobile phone text messages between clients with dual diagnosis and a clinician who engaged them in daily assessment and intervention text exchanges. METHODS: Seventeen participants with psychotic disorders and substance use were enrolled in a 12-week single-arm trial of an mHealth intervention focusing on illness management. The clinician (i.e., mobile interventionist) sent daily text messages to participants' privately owned mobile phones to assess their medication adherence and clinical status. The clinician provided other illness management and wellness suggestions flexibly, in response to participants' needs and preferences. In this qualitative study we conducted a thematic analysis of the client-clinician text exchanges that occurred over the course of the intervention. RESULTS: Seven major content themes in client-clinician text message exchanges were identified: mental health symptoms; mental health coping strategies; mental health treatment and management; lifestyle behaviors; social relationships and leisure activities; motivation and personal goal setting; and independent living. Participants were interested in discussing strategies for coping with mental health symptoms (e.g., cognitive restructuring, social support) and health behavior change (e.g., increased physical activity, dietary changes). CONCLUSIONS: Our findings suggest that client-centered text messaging has the potential to be an important component of illness management for people with dual diagnosis. This approach is able to offer coping strategies that are tailored to clients' needs and preferences in real time when help is needed. PMID- 26829357 TI - The role of biomarkers and imaging in Parkinson's disease. AB - The diagnosis of Parkinson's disease (PD) currently relies on the appearance of certain clinical features. However, these features appear only years after the loss of nigral dopaminergic neurons. The progression of PD may be measured using clinical rating scales that are subjective and that have a variable inter-rater consistency. There is a growing need for a biomarker that will allow for early detection of the disease as well as provide a measure of disease progression. In this article, we review different biomarkers, with a focus on functional imaging techniques, which while imperfect, currently provide the best approach to this problem. We also discuss the use of structural imaging and emerging progress in other biochemical and molecular markers. While there is no single biomarker that will satisfy all requirements, a combination is likely to be of great use in identifying those subjects most likely to benefit from neuroprotective therapies, as well as in monitoring the effects of any interventions. PMID- 26829358 TI - Wild fauna as a carrier of Salmonella in Reunion Island: Impact on pig farms. AB - Salmonellosis is an economic burden to the livestock industry in Reunion Island. In this study, we wanted to improve our understanding of Salmonella epidemiology by studying the wild fauna of Reunion Island. We assessed Salmonella diversity in small non-flying mammals, birds and cockroaches in order to evaluate their potential role in the epidemiology of Salmonella. A total of 268 samples were collected from cockroaches, small mammals and birds. The bacteriological analyses revealed that 11.7% of non-flying mammals and 25% of cockroaches tested were Salmonella infected; two wild bird species were also detected positive. The 128 Salmonella isolates were distributed in fifteen serotypes and the most predominant were S. 4,[5],12:i:- (21.9% of positive samples) followed by S. Enteritidis (15.6%), S. Typhimurium (15.6%), S. Infantis (12.5%) and S. Weltevreden (12.5%). A total of 27 XbaI profiles were identified using pulsed field gel electrophoresis. Comparison of these Salmonella strains with our collection of Salmonella isolated from pigs and pig farm environments at the same period revealed 14 strains in common between wild fauna and pigs, especially for cockroaches. Our results suggest that wild fauna of Reunion Island could be infected by strains of Salmonella also isolated from pigs or pig environment. They may play a role in both persistence and spreading of Salmonella and therefore, could be a source of infection in pig farms. Pest control against cockroaches could be a helpful tool in the reduction of Salmonella infection of pigs, limiting contacts between wild fauna and both pigs and pig environment. Special attention should be paid to S. 4,[5],12:i:- since it was predominant in Reunion Island's wild fauna and pigs and was the third most frequently reported serotype in human salmonellosis in Europe. PMID- 26829359 TI - Detection of Culex flavivirus and Aedes flavivirus nucleotide sequences in mosquitoes from parks in the city of Sao Paulo, Brazil. AB - The dengue viruses are widespread in Brazil and are a major public health concern. Other flaviviruses also cause diseases in humans, although on a smaller scale. The city of Sao Paulo is in a highly urbanized area with few green spaces apart from its parks, which are used for recreation and where potential vertebrate hosts and mosquito vectors of pathogenic Flavivirus species can be found. Although this scenario can contribute to the transmission of Flavivirus to humans, little is known about the circulation of members of this genus in these areas. In light of this, the present study sought to identify Flavivirus infection in mosquitoes (Diptera: Culicidae) collected in parks in the city of Sao Paulo. Seven parks in different sectors of the city were selected. Monthly mosquito collections were carried out in each park from March 2011 to February 2012 using aspiration and traps (Shannon and CD C-CO2). Nucleic acids were extracted from the mosquitoes collected and used for reverse-transcriptase and real-time polymerase chain reactions with genus-specific primers targeting a 200 nucleotide region in the Flavivirus NS5 gene. Positive samples were sequenced, and phylogenetic analyses were performed. Culex and Aedes were the most frequent genera of Culicidae collected. Culex flavivirus (CxFV)-related and Aedes flavivirus (AEFV)- related nucleotide sequences were detected in 17 pools of Culex and two pools of Aedes mosquitoes, respectively, among the 818 pools of non engorged females analyzed. To the best of our knowledge, this is the first report of CxFV and AEFV in the city of Sao Paulo and Latin America, respectively. Both viruses are insect- specific flaviviruses, a group known to replicate only in mosquito cells and induce a cytopathic effect in some situations. Hence, our data suggests that CxFV and AEFV are present in Culex and Aedes mosquitoes, respectively, in parks in the city of Sao Paulo. Even though Flavivirus species of medical importance were not detected, surveillance is recommended in the study areas because of the presence of vertebrates and mosquitoes that could act as amplifying hosts and vectors of flaviviruses, providing the required conditions for circulation of these viruses. PMID- 26829361 TI - Efficacy of a modified coagulation factor substitution for total hip arthroplasty in patients with end-stage haemophilic arthropathy. AB - Total hip arthroplasty (THA) is an effective treatment for end-stage haemophilic arthropathy, and substitution therapy plays a key role in the success of THA. The aim of this study was to evaluate the efficacy of a modified coagulation factor substitution regime in THA. Nineteen haemophiliac patients (20 hips) who received primary cementless THA were enrolled. Based on World Federation of Haemophilia (WFH) guideline, a modified coagulation factor substitution regime was adopted. Blood loss, implant survival rates and complications were reviewed, retrospectively. The mean age at surgery was 29.7 years (15-49 years) and the mean follow-up period was 91 months (43-151 months). Mean total blood loss, external blood loss and hidden blood loss were 3543 (1494-7576), 1435 (600-3440), and 2110 ml (534-4402), respectively. Mean intraoperative blood loss and postoperative drainage were 715 (300-2000) and 713 ml (200-2950), respectively. Mean red blood cell transfusion used was 5 U (0-14). All prostheses were found to have bony ingrowth. One patient had hematoma formation in the thigh and one with a lower limb deep vein thrombosis, postoperatively. Other complications included one skin ulcer, one femur splitting fracture, and one transient neuropraxia. Intraoperative blood loss and wound drainage, in our study, were similar to that in haemophiliac patients and nonhaemophilic patients in literature. This supports the efficacy of the modified coagulation factor substitution strategy in our study. PMID- 26829362 TI - Pulmonary embolism in congenital bleeding disorders: intriguing discrepancies among different clotting factors deficiencies. AB - Pulmonary embolism is a complication of deep vein thrombosis. It occurs in the population with a normal clotting mechanism, but it may also occur in patients with congenital bleeding conditions. Here, we report on all cases of pulmonary embolism in congenital hemorrhagic disorders. All reported cases of pulmonary embolism in congenital coagulation disorders have been gathered by a time unlimited PubMed search. Cross-checking of the references listed at the end of the single papers was carried out to avoid omissions. Seventy-two patients had an objectively demonstrated pulmonary embolism. The event occurred in patients with fibrinogen, factor V, factor VIII (FVII), FVIII, FIX, and FXI deficiency, and in those with von Willebrand's disease. No embolism was reported in FII, factor X, and FXIII deficiency. Thirty were women and 28 were men, whereas in the remaining 14 cases, sex was not reported. Age varied from 6 to 81 years (mean age 34.3 years). The management varied from only supportive to the administration of unfractionated heparin, low-molecular-weight heparin, and anti-vitamin K medications, accompanied by adequate replacement therapy. Evolution was fair or good in the majority of cases, but there were 10 fatalities. Risk factors were present in 61 patients. The most frequent of these were replacement therapy (35 cases), surgery (34), and old age (13). Some patients had more than one risk factor. Eleven patients had no risk factors. There are discrepancies in the prevalence of pulmonary embolism among different clotting disorders. The conditions most frequently affected are FVII deficiency and fibrinogen defects. The significance of the findings is discussed. PMID- 26829360 TI - Long-term immune responses and comparative effectiveness of one or two doses of 7 valent pneumococcal conjugate vaccine (PCV7) in HIV-positive adults in the era of combination antiretroviral therapy. AB - INTRODUCTION: HIV infection impairs maintenance of immunological memory, yet few studies of HIV-positive adults receiving 7-valent pneumococcal conjugate vaccine (PCV7) have followed them beyond the first year. We determined and compared the durability of serological responses and the clinical outcomes of HIV-positive adults annually for five years following vaccination with one or two doses of PCV7. METHODS: In this non-randomized clinical trial, 221 pneumococcal vaccine naive HIV-positive adults receiving one (n = 109) or two doses four weeks apart (n = 112) of PCV7 between 2008 and 2010 were longitudinally followed for evaluation of significant serological response and for episodes of pneumonia and invasive pneumococcal disease. RESULTS: At the time of vaccination, the two groups were well matched for age, risk factors, combination antiretroviral therapy (cART) coverage, CD4 count and plasma HIV RNA load (PVL). At the end of five years, the CD4 counts for the one- and two-dose groups had increased from 407 and 406 to 550 and 592 cells/uL, respectively, and 82.4 and 81.6% of the participants had fully suppressed PVL. Significant immune responses to >= 2 serotypes persisted for 67.9 vs 78.6%, 64.2 vs 71.4%, 66.1 vs 71.4%, 57.8 vs 69.6% in the second, third, fourth and fifth years after one and two doses of PCV7 in the intention-to-treat analysis, respectively. In multivariate analysis, immunization with two doses of PCV7 (odds ratio (OR) 1.71, 95% confidence interval (CI) 1.10 to 2.65, p = 0.016), concurrent cART (OR 2.16, 95% CI 1.16 to 4.00, p = 0.015) and CD4 proliferation (OR 1.12, 95% CI 1.01 to 1.27, p = 0.031) were predictive of persistent serological responses in the fifth year. Only one patient in the one-dose group had documented pneumococcal pneumonia (non bacteraemic) and none had invasive pneumococcal disease in the 6.5 years of follow-up. CONCLUSIONS: One or two doses of PCV7 achieve durable seroprotective responses in HIV-treated participants; however, two doses may be more robust than one dose in a larger study population or in real-world populations with less cART coverage. PMID- 26829363 TI - Platelet abnormalities in adults with severe pulmonary arterial hypertension related to congenital heart defects (Eisenmenger syndrome). AB - Patients with severe pulmonary arterial hypertension suffer from life-threatening thrombotic and bleeding complications. The aim of this study was to compare selected platelet, endothelial, and coagulation parameters in healthy volunteers and patients with severe pulmonary arterial hypertension because of congenital heart defects. The study included healthy volunteers (n = 50) and patients with cyanotic congenital heart defects classified as Eisenmenger syndrome (n = 41). We investigated platelet count, mean platelet volume, and platelet aggregation - spontaneous and induced by various concentrations of five agonists. Von Willebrand factor (vWF), fibrinogen, factor VIII and XII, plasminogen activator inhibitor, antithrombin, D-dimer, and antiphospholipid antibodies were also investigated. We found a decreased platelet count [190 (147-225) vs. 248 (205 295) 10 l, P < 0.0001], higher mean platelet volume [10.9 (10.1-12.0) vs. 10.2 (9.4-10.4) fl, P < 0.0001], and significantly decreased platelet aggregation (induced by five agonists, in various concentrations) in patients with Eisenmenger syndrome compared with controls. These changes were accompanied by an increase of plasma vWF antigen [141.6 (108.9-179.1) vs. 117.4 (9.2-140.7) IU/dl, P = 0.022] and serum anti-beta2-glycoprotein [2.07 (0.71-3.41) vs. 0.47 (0.18 0.99) U/ml, P < 0.0001]. Eisenmenger syndrome is accompanied by platelet abnormalities. Thrombocytopenia with increased platelet size is probably due to a higher platelet turnover associated with platelet activation. Impaired platelet aggregation can reflect specific platelet behaviour in patients with Eisenmenger syndrome. These changes can be related both to bleeding and to thrombotic events. A higher vWF antigen may be a consequence of endothelial damage in Eisenmenger syndrome, but the cause for an increase of anti-beta2-glycoprotein is unknown. PMID- 26829364 TI - Stimulatory effect of an algal fucoidan on the release of vascular endothelial tissue-type plasminogen activator as a mechanism of fucoidan-mediated thrombolysis. AB - Identifying a pharmacological means for increasing the production of tissue-type plasminogen activator (t-PA) is always desirable to cure impaired production of this enzyme. An algal fucoidan has been shown to exhibit both novel thrombolytic and synergistic stimulatory effects in a mouse thrombosis model. The plasma levels of active t-PA were measured in mouse arterial thrombus models that were treated with various fucoidans to investigate the mechanism of thrombolysis. The mean plasma level of active t-PA after the infusion of fucoidan was 2.136 +/- 0.231 ng/ml for nonthrombolytic Fucus fucoidan and 3.917 +/- 0.0.529 ng/ml for thrombolytic Undaria fucoidan, which resulted in a 1.56-2.29-fold increase compared with the healthy control group (1.706 +/- 0.194 ng/ml) and the untreated thrombus group (2.506 +/- 0.301 ng/ml) (P < 0.01). An algal fucoidan has demonstrated to exert a thrombolytic and stimulatory effect via the induction of t-PA release in a dose-dependent manner in an arterial thrombosis model. PMID- 26829365 TI - Ascorbate inhibits platelet-endothelial adhesion in an in-vitro model of sepsis via reduced endothelial surface P-selectin expression. AB - Plugging of the capillary bed can lead to organ failure and mortality in sepsis. We have reported that intravenous ascorbate injection reduces platelet adhesion to the capillary wall and capillary plugging in septic mice. Both platelet adhesion and capillary plugging require P-selectin, a key adhesion molecule. To elucidate the beneficial effect of ascorbate, we hypothesized that ascorbate reduces platelet-endothelial adhesion by reducing P-selectin surface expression in endothelial cells. We used mouse platelets, and monolayers of cultured microvascular endothelial cells (mouse skeletal muscle origin) stimulated with lipopolysaccharide, to examine platelet-endothelial adhesion. P-selectin mRNA expression in endothelial cells was determined by real-time PCR and P-selectin protein expression at the surface of these cells by immunofluorescence. Secretion of von Willebrand factor from cells into the supernatant (a measure of P-selectin containing granule exocytosis) was determined by ELISA. Lipopolysaccharide (10 MUg/ml, 1 h) increased platelet-endothelial adhesion. P-selectin-blocking antibody inhibited this adhesion. Lipopolysaccharide also increased P-selectin mRNA in endothelial cells, P-selectin expression at the endothelial surface, and von Willebrand factor secretion. Ascorbate pretreatment (100 MUmol/l, 4 h) inhibited the increased platelet adhesion, surface expression of P-selectin, and von Willebrand factor secretion, but not the increase in P-selectin mRNA. The lipopolysaccharide-induced increase in platelet-endothelial adhesion requires P selectin presence at the endothelial surface. Ascorbate's ability to reduce this presence could be important in reducing both platelet adhesion to the capillary wall and capillary plugging in sepsis. PMID- 26829366 TI - Global Post-Authorization Safety Surveillance Study: real-world data on prophylaxis and on-demand treatment using FEIBA (an activated prothrombin complex concentrate). AB - This prospective, Post-Authorization Safety Surveillance (PASS) study was carried out in patients with hemophilia A or B and inhibitors treated with FEIBA for 1 year to collect real-world data on safety and effectiveness of FEIBA. The study followed a cohort design and did not make stipulations on treatment or observation schedule, as it was designed to observe routine medical practices based on physicians' treatment decisions, including whether patients received on demand or prophylaxis with FEIBA. The attending physician maintained documentation, including medical records, laboratory reports, adverse event reports, and so on and a subject diary was used. Eighty-one patients were treated with FEIBA at 40 sites in 10 countries over a 4-year period. Sixty-nine patients (85.2%) had hemophilia A, two had (2.5%) hemophilia B, and ten (12.3%) had acquired hemophilia A. At baseline 45 patients (55.6%) were prescribed prophylaxis and 36 (44.6%) on-demand treatment. This study was novel in following safety and effectiveness in 'real world' on-demand and prophylactic use of FEIBA, and was able to collect data in these rare patients under routine clinical practice. PMID- 26829367 TI - Tic Disorders and Tourette Syndrome: Current Concepts of Etiology and Treatment in Children and Adolescents. AB - Tic disorders (TD), including chronic/persistent TD (CTD) and Tourette syndrome, have been described and studied for many years. Within the last two decades, intensified study efforts led to more specific assumptions about genesis and influences of both hereditary and environmental factors. TD in children and adolescents are very often accompanied by attention-deficit/hyperactivity disorders and obsessive-compulsive disorders (OCD) as comorbid disorders. Comorbidities are aggravating factors concerning prognosis and treatment opportunities. Therefore, etiological considerations and treatment strategies have to take associated psychiatric disorders into account. Treatment approaches are symptom targeted and include behavioral treatments and/or medication and show positive outcomes concerning tic symptomatology, global functioning, and associated psychopathology. This review presents an update of the research, definitions, and classification according to ICD-10 and DSM-5 and summarizes the diagnostic procedures and most effective clinical strategies. PMID- 26829368 TI - Characterization and Higher-Order Structure Assessment of an Interchain Cysteine Based ADC: Impact of Drug Loading and Distribution on the Mechanism of Aggregation. AB - The impact of drug loading and distribution on higher order structure and physical stability of an interchain cysteine-based antibody drug conjugate (ADC) has been studied. An IgG1 mAb was conjugated with a cytotoxic auristatin payload following the reduction of interchain disulfides. The 2-D LC-MS analysis shows that there is a preference for certain isomers within the various drug to antibody ratios (DARs). The physical stability of the unconjugated monoclonal antibody, the ADC, and isolated conjugated species with specific DAR, were compared using calorimetric, thermal, chemical denaturation and molecular modeling techniques, as well as techniques to assess hydrophobicity. The DAR was determined to have a significant impact on the biophysical properties and stability of the ADC. The CH2 domain was significantly perturbed in the DAR6 species, which was attributable to quaternary structural changes as assessed by molecular modeling. At accelerated storage temperatures, the DAR6 rapidly forms higher molecular mass species, whereas the DAR2 and the unconjugated mAb were largely stable. Chemical denaturation study indicates that DAR6 may form multimers while DAR2 and DAR4 primarily exist in monomeric forms in solution at ambient conditions. The physical state differences were correlated with a dramatic increase in the hydrophobicity and a reduction in the surface tension of the DAR6 compared to lower DAR species. Molecular modeling of the various DAR species and their conformers demonstrates that the auristatin-based linker payload directly contributes to the hydrophobicity of the ADC molecule. Higher order structural characterization provides insight into the impact of conjugation on the conformational and colloidal factors that determine the physical stability of cysteine-based ADCs, with implications for process and formulation development. PMID- 26829369 TI - Validation of the Spanish version of the Drive for Muscularity Scale (DMS) among males: Confirmatory factor analysis. AB - Drive for Muscularity (DM) has been shown to be a relevant construct for measuring and understanding male body image. For this reason, it is important to have reliable and valid instruments with which to measure DM, and to date no such instruments exist in Spain. This study analyzes the psychometric and structural properties of the Drive for Muscularity Scale (DMS) in a sample of Spanish adolescent males (N=212), with the aim of studying the structural validity of the scale by using a confirmatory factor analysis (CFA), as well as analyzing the internal consistency and construct (convergent and discriminant) and concurrent validity of the instrument. After testing three models, results indicated that the best structure was a two-dimensional model, with the factors of muscularity oriented body image (MBI) and muscularity behavior (MB). The scale showed good internal consistency (alpha=.90) and adequate construct validity. Furthermore, significant associations were found between DM and increased difficulties in emotional regulation (rho=.37) and low self-esteem (rho=-.19). Findings suggest that the two-factor structure may be used when assessing drive for muscularity among adolescent males in Spain. PMID- 26829370 TI - Internalized weight stigma moderates eating behavior outcomes in women with high BMI participating in a healthy living program. AB - Weight stigma is a significant socio-structural barrier to reducing health disparities and improving quality of life for higher weight individuals. The aim of this study was to examine the impact of internalized weight stigma on eating behaviors after participating in a randomized controlled trial comparing the health benefits of a weight-neutral program to a conventional weight-management program for 80 community women with high body mass index (BMI > 30, age range: 30 45). Programs involved 6 months of facilitator-guided weekly group meetings using structured manuals. Assessments occurred at baseline, post-intervention (6 months), and 24-months post-randomization. Eating behavior outcome measurements included the Eating Disorder Examination-Questionnaire and the Intuitive Eating Scale. Intention-to-treat linear mixed models were used to test for higher-order interactions between internalized weight stigma, group, and time. Findings revealed significant 3-way and 2-way interactions between internalized weight stigma, group, and time for disordered and adaptive eating behaviors, respectively. Only weight-neutral program participants with low internalized weight stigma improved global disordered eating scores. Participants from both programs with low internalized weight stigma improved adaptive eating at 6 months, but only weight-neutral program participants maintained changes at follow up. Participants with high internalized weight stigma demonstrated no changes in disordered and adaptive eating, regardless of program. In order to enhance the overall benefit from weight-neutral approaches, these findings underscore the need to incorporate more innovative and direct methods to reduce internalized weight stigma for women with high BMI. PMID- 26829371 TI - Weight stigma and eating behavior: A review of the literature. AB - Weight stigma is a pervasive social problem, and this paper reviews the evidence linking weight stigma to eating behavior. Correlational studies consistently find that experiences with weight stigma are associated with unhealthy eating behaviors and eating pathology (such as binge eating, skipping meals), although results vary somewhat depending on the sample being studied and the specific stigma/eating constructs being assessed. Experimental studies consistently find that manipulations such as priming overweight stereotypes, exposure to stigmatizing content, and social exclusion all lead to increased food intake, but whether or not those manipulations capture the impact of weight stigma experiences per se is less clear. Finally, studies of stigma experiences in daily life show that more frequent stigma experiences are associated with decreased motivation to diet and with less healthy eating behaviors. Overall, this research highlights the potential for weight stigma to negatively impact individuals' eating behavior, which in turn could have consequences for their overall health and well-being. PMID- 26829372 TI - Mimicking the Humidity Response of the Plant Cell Wall by Using Two-Dimensional Systems: The Critical Role of Amorphous and Crystalline Polysaccharides. AB - Of the composite materials occurring in nature, the plant cell wall is among the most intricate, consisting of a complex arrangement of semicrystalline cellulose microfibrils in a dissipative matrix of lignin and hemicelluloses. Here, a biomimetic, two-dimensional cellulose system of the cell wall structure is introduced where cellulose nanocrystals compose the crystalline portion and regenerated amorphous cellulose composes the dissipative matrix. Spectroscopic ellipsometry and QCM-D are used to study the water vapor uptake of several two layer systems. Quantitative analysis shows that the vapor-induced swelling of these ultrathin films can be controlled by varying ratios of the chemically identical ordered and unordered cellulose components. Intriguingly, increasing the share of crystalline cellulose appeared to increase the vapor uptake but only in cases for which the interfacial area between the crystalline and amorphous area was relatively large and the thickness of an amorphous overlayer was relatively small. The results show that a biomimetic approach may occasionally provide answers as to why certain native structures exist. PMID- 26829373 TI - Antibacterial Effects of Biosynthesized Silver Nanoparticles on Surface Ultrastructure and Nanomechanical Properties of Gram-Negative Bacteria viz. Escherichia coli and Pseudomonas aeruginosa. AB - Understanding the interactions of silver nanoparticles (AgNPs) with the cell surface is crucial for the evaluation of bactericidal activity and for advanced biomedical and environmental applications. Biosynthesis of AgNPs was carried out through in situ reduction of silver nitrate (AgNO3) by cell free protein of Rhizopus oryzae and the synthesized AgNPs was characterized by UV-vis spectroscopy, high resolution transmission electron microscopy (HRTEM), dynamic light scattering (DLS), zeta-potential analysis, and FTIR spectroscopy. The HRTEM measurement confirmed the formation of 7.1 +/- 1.2 nm AgNPs, whereas DLS study demonstrated average hydrodynamic size of AgNPs as 9.1 +/- 1.6 nm. The antibacterial activity of the biosynthesized AgNPs (zeta = -17.1 +/- 1.2 mV) was evaluated against Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa. The results showed that AgNPs exhibited concentration dependent antibacterial activity and 100% killing of E. coli and P. aeruginosa achieved when the cells were treated with 4.5 and 2.7 MUg/mL AgNPs, respectively for 4 h. Furthermore, the intracellular reactive oxygen species (ROS) production suppressed the antioxidant defense and exerted mechanical damage to the membrane. AgNPs also induced surface charge neutralization and altered of the cell membrane permeability causing nonviability of the cells. Atomic force microscopy (AFM) studies depicted alteration of ultrastructural and nanomechanical properties of the cell surface following interaction with AgNPs, whereas FTIR spectroscopic analysis demonstrated that cell membrane of the treated cells underwent an order to-disorder transition during the killing process and chemical composition of the cell membrane including fatty acids, proteins, and carbohydrates was decomposed following interaction with AgNPs. PMID- 26829374 TI - Management of nipple-areolar complex complications in skin-sparing mastectomy with prosthetic reconstruction A case report. AB - INTRODUCTION AND OBJECCTIVES: Venous congestion of the NAC (Nipple-Areola Complex) is not an uncommon complication of Skin-Reducing Mastectomy (SRM). The correct and prompt evaluation of the NAC's vitality in the first hours after surgery is important for the survival of the same, in fact the possibility of early intervention allows avoiding the use of invasive and radicals techniques to the advantage of simpler rapid procedures. MATERIALS AND METHODS: DM, 57yr, multiple invasive ductal carcinoma of the right breast, underwent a SRM and immediate reconstruction with implant in August 2014 In the immediate post operative appeared a venous stasis of the NAC. Treatment started with Negative Pressure Wound Therapy (NWPT) through VAC-Systems to 75 mmHg. RESULTS: The use of the VAC-Therapy was in total 12 days and allowed the partial rescue of the NAC (85%). the vacuum pump is put into a portable bag so the patient's mobility is not limited. DISCUSSION: NWPT permitted a rapid resolution of NAC's complication in SRM in order to guarantee an optimal timing for the start of adjuvant chemotherapy. The VAC-Therapy is a cost effective and simple to use in cases of suffering venous NAC in patients undergoing breast surgery. KEY WORDS: NAC, NWPT, Skin-Reducing Mastectomy, VAC-Therapy. PMID- 26829375 TI - Accounting for the Dynamic Oxidative Behavior of Nickel Anodes. AB - The dynamic behavior of the anodic peak for amorphous nickel oxy/hydroxide (a NiOx) films in basic media was investigated. Chronocoulometry of films with known nickel concentrations reveals that a total of four electrons per nickel site comprise the signature anodic peak at 1.32 V during the first oxidative scan, and two electrons are passed through the associated cathodic peak on the reverse scan. The anodic and cathodic signals each contain two electrons on the successive scans. Catalytic oxygen evolution reaction (OER) was detected within the anodic peak, which is at a lower potential than is widely assumed. In order to rationalize these experimental results, we propose that the four-electron oxidation event is the conversion of the film from nickel(II) hydroxide ([Ni(II) OH](-)) to a higher valent nickel peroxide species (e.g., Ni(IV)-OO or Ni(III) OO.). The subsequent reduction of the nickel peroxide species is confined by a chemical step resulting in the accumulation of [Ni(II)-OOH](-), which is then oxidized by two electrons to form Ni(IV)-OO during the subsequent oxidative scan on the time scale of a cyclic voltammetric experiment. Our proposed mechanism and the experimental determination that each nickel site is oxidized by four electrons helps link the myriad of seemingly disparate literature data related to OER catalysis by nickel electrodes. The faster catalysis that occurs at higher oxidative potentials is derived from a minority species and is not elaborated here. PMID- 26829376 TI - Memorable Experiences in Therapeutic Assessment: Inviting the Patient's Perspective Following a Pretreatment Randomized Controlled Trial. AB - Accumulating evidence documents the efficacy of Therapeutic Assessment (TA) in terms of symptom reduction and other outcomes, but only minimal data speak to the patient's perspective of what is memorable, or potentially important, about this intervention. In line with the humanistic and phenomenological philosophy of TA, we solicited patient input by asking personality disorder (PD) patients who participated in a recent randomized controlled trial (De Saeger et al., 2014 ) about their experiences. We report on 10 PD patients who were administered semistructured interviews designed to assess an in-depth perspective of undergoing TA. Our methodological approach can be described as phenomenological and integrative, approximating guidelines provided by the Consensual Qualitative Research paradigm (Hill, 2012 ). Four core content domains emerged from the transcribed and coded interview protocols: (a) relationship aspects, (b) new insight into personal dynamics, (c) sense of empowerment, and (d) validation of self. Novel experiences were mostly of a relational nature, and pertained to feeling of being treated like an equal and essential partner in a highly individualized venture. Research and clinical implications of these patient reports of TA participation are discussed. PMID- 26829377 TI - Unfolded protein response gene GADD34 is overexpressed in rheumatoid arthritis and related to the presence of circulating anti-citrullinated protein antibodies. AB - Growth arrest and DNA damage-inducible gene 34 (GADD34) is an inducible cofactor of protein phosphatase 1, which has an important role in the unfolded protein response. GADD34 has been shown to be necessary for type I interferon and proinflammatory cytokine production in response to viral infection in murine models. We investigate the expression of GADD34 in rheumatoid arthritis (RA), in which proinflammatory cytokines have an important pathogenic role. The objective of this study was to evaluate the potential of GADD34 expression as a biomarker in RA patients. We report a case-control study on GADD34 gene expression in peripheral blood mononuclear cells of patients (n = 75) with RA and age- and sex matched healthy controls (n = 25). The study was approved by the relevant local ethics committees. GADD34 gene expression level in peripheral blood mononuclear cells was measured by quantitative PCR and analyzed with Mann-Whitney test. The relation between GADD34 gene overexpression and clinical or biological characteristics was analyzed with univariate and multivariate analysis. GADD34 gene expression was significantly higher in RA patients compared with healthy controls (p <= 0.001). Interestingly, GADD34 overexpression in PBMC of patients was related to the presence of circulating anti-citrullinated protein antibodies (p = 0.030). Data of this study strengthen the evidence of an unfolded protein response during the course of RA and provide an insight of the potential interest in GADD34 as a relevant marker for RA. PMID- 26829378 TI - Co-milling of telmisartan with poly(vinyl alcohol)--An alkalinizer free green approach to ensure its bioavailability. AB - The aim of this study was to enhance the dissolution and bioavailability of telmisartan (TLM), a poorly water soluble drug by co-milling approach. Physical mixtures of TLM and poly(vinyl alcohol) (PVA) were co-milled in a planetary micro mill in a dry condition by varying process parameters such as drug to polymer weight ratio, ball-to-powder weight ratio, and rotational speed. The co-milled products offered cumulative percentage dissolution of TLM above 75% in 30 min (CG 1 and CG2). These samples were characterized using field emission scanning electron microscopy (FE-SEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and Raman spectra analysis. Well-dispersed acicular shaped particles of TLM were observed in co-milled products. A mixture of crystalline and amorphous TLM with a particle size less than 1 MUm was present in CG1. The particle size of TLM observed in CG2 was less than 2 MUm. In addition to crystalline and amorphous form of TLM, defective/disordered crystals of TLM were also present in CG 2. Therefore, CG2 tablets exhibited poor stability. CG 1 tablets were found to be stable under accelerated stability test conditions. The relative bioavailability of TLM of CG 1 containing tablets in comparison with Micardis(r) was 93.92+/-12.84% (in rabbits). Thus, co-milling of TLM with PVA proves to be a promising "alkalinizer free green approach" to ensure the dissolution and bioavailability of poorly water soluble TLM. PMID- 26829379 TI - Effect of polymer microstructure on the docetaxel release and stability of polyurethane formulation. AB - PurSil(r)AL20 (PUS), a copolymer of 4,4'-dicyclohexylmethane diisocyanate (HMDI), 1,4-butane diol (BD), poly-tetramethylene oxide (PTMO) and poly-dimethyl siloxane (PDMS) was investigated for stability as a vehicle for Docetaxel (DTX) delivery through oesophageal drug eluting stent (DES). On exposure to stability test conditions, it was found that DTX release rate declined at 4 and 40 degrees C. In order to divulge reasons underlying this, changes in DTX solid state as well as PUS microstructure were followed. It was found that re-crystallization of DTX in PDMS rich regions was reducing the drug release at both 4 degrees C and 40 degrees C samples. So far microstructural features have not been correlated with stability and drug release, and in this study we found that at 40 degrees C increase in microstructural domain sizes and the inter-domain distances (from ~85 A to 129 A) were responsible for hindering the DTX release in addition to DTX re crystallization. PMID- 26829380 TI - Trehalose phosphate synthase overexpression in Parachlorella kessleri improves growth and photosynthetic performance under high light conditions. AB - Parachlorella kessleri is a promising oil-bearing marine alga which shows decreased growth under high light stress. Osmolytes are known to relieve stress by protecting the cell membrane, proteins, and enzymes. Enhanced production of osmolyte (trehalose) was thus used to relieve stress in P. kessleri by overexpression of trehalose phosphate synthase (TPS) gene. Transformed P. kessleri was grown under different light regimes to study the effect of trehalose overproduction on growth. Study of one of the TPS transformants showed increased trehalose as well as increased biomass and decreased pigments, reactive oxygen species, and lipid peroxidation of cell membrane. The improved photosynthetic performance of the transformant was also signified by pulse-amplitude-modulated fluorometric analysis. All of these factors reveal improved stress tolerance under high light conditions by increased trehalose accumulation due to TPS overexpression in P. kessleri. PMID- 26829381 TI - Functional genomics of candidate genes derived from genome-wide association studies for five common neurological diseases. AB - AIM: Recent genome-wide association studies (GWAS) are identifying novel candidate genes for several neurological diseases (NDs). However, a global functional analysis of those genes derived from GWAS for NDs is missing. We explored the genomic and functional features of novel candidate genes for five common NDs: Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke and migraine. MATERIALS AND METHODS: A functional enrichment analysis was performed for GWAS-derived genes, for categories such as Kyoto Encyclopedia of Genes and Genomes pathways, gene expression, InterPro domains, transcription factor binding sites, gene ontology (GO) terms and microRNA (miRNA) targets. An analysis of protein-protein interactions was carried out. RESULTS: Six hundred and forty-two unique single nucleotide polymorphisms (SNPs) were identified for the five NDs and 2.3% of them were non-synonymous SNPs. There were no common SNPs for all five NDs and eight genes were associated with more than one ND. The enrichment analysis showed significant values for several GO categories, such as cell-cell adhesion and location in neurites and for expression in prefrontal cortex. An analysis of protein-protein interactions showed the evidence of a large component. Fifty-one of these GWAS-derived genes are known to be potentially druggable and twelve are known to harbor mutations for neuropsychiatric disorders. CONCLUSIONS: Our results suggest that there is little overlap between the genes identified in GWAS for the five common NDs. Identification of functional categories in the GWAS-derived candidate genes for common NDs could lead to a better understanding of their functional consequences and could be useful for the future discovery of additional genetic risk factors for those diseases. PMID- 26829383 TI - Adaptation of influenza A(H1N1)pdm09 virus in experimental mouse models. AB - In the present study, three mouse-adapted variants of influenza A(H1N1)pdm09 virus were obtained by lung-to-lung passages of BALB/c, C57BL/6z and CD1 mice. The significantly increased virulence and pathogenicity of all of the mouse adapted variants induced 100% mortality in the adapted mice. Genetic analysis indicated that the increased virulence of all of the mouse-adapted variants reflected the incremental acquisition of several mutations in PB2, PB1, HA, NP, NA, and NS2 proteins. Identical amino acid substitutions were also detected in all of the mouse-adapted variants of A(H1N1)pdm09 virus, including PB2 (K251R), PB1 (V652A), NP (I353V), NA (I106V, N248D) and NS1 (G159E). Apparently, influenza A(H1N1)pdm09 virus easily adapted to the host after serial passages in the lungs, inducing 100% lethality in the last experimental group. However, cross-challenge revealed that not all adapted variants are pathogenic for different laboratory mice. Such important results should be considered when using the influenza mice model. PMID- 26829382 TI - The -308 bp TNF gene polymorphism influences tumor necrosis factor expression in leprosy patients in Bahia State, Brazil. AB - Leprosy or Hansen's disease is a debilitating chronic granulomatous disease caused by Mycobacterium leprae, with high incidence and prevalence in Brazil. The -308 bp G/A single nucleotide polymorphism (SNP rs1800629) in the tumor necrosis factor (TNF) gene promoter is a proposed risk factor for leprosy. In Brazil, Northern India, Egypt and Nepal, the common G allele was associated with leprosy. In Eastern India, Thailand and Malawi the minor A allele was the risk factor. Allele A was previously associated with high TNF. We genotyped rs1800629 in 326 leprosy cases from Bahia State, Brazil, including 72 paucibacillary (PB) and 47 multibacillary (MB) without reactions, and 69 reversal reaction (RR) and 78 erythema nodosum leprosum (ENL) with reactions. Logistic regression was used to compare patient groups with 331 healthy controls. Relative TNF mRNA was determined in peripheral blood leukocytes by QRTPCR, and serum TNF levels measured by ELISA. We found that TNF mRNA expression was higher (P=0.03) in leprosy patients compared to endemic controls, but did not differ significantly between clinical subgroups. Carriage of the minor A allele was associated (P=0.003) with low TNF mRNA across leprosy patients. Nevertheless, we found no evidence for either allele at this SNP as a risk factor for leprosy per se (OR=1.12, 95% CI 0.79-1.60, P=0.52), PB (OR=0.99, 95% CI 0.54-1.81, P=0.97), MB (OR=0.86, 95% CI 0.40-1.83, P=0.70), RR (OR=1.37, 95% CI 0.79-2.38, P=0.27) or ENL (OR=0.76, 95% CI 0.40-1.45, P=0.42) when compared to endemic controls. Further studies are required to determine whether the influence of the minor A allele on TNF mRNA levels determines response to treatment, particularly in the context of ENL reaction treatment with anti-TNF therapies and RR reactions where treatment with prednisolone is known to reduce TNF levels. Our findings contribute to understanding TNF as an important determinant of leprosy immunopathology in Brazil. PMID- 26829385 TI - MiR-20a and miR-20b negatively regulate autophagy by targeting RB1CC1/FIP200 in breast cancer cells. AB - AIMS: RB1CC1/FIP200 was essential for autophagosome formation. Therefore, RB1CC1/FIP200 cellular levels are critical for the activation of the autophagy pathways. Following the screen of miRNAs affecting RB1CC1/FIP200 level and rapamycin-induced autophagy, we discovered miR-20a and miR-20b could regulate autophagy by targeting RB1CC1/FIP200. MAIN METHODS: Inhibitory effect of miR-20a and 20b on basal and rapamycin-stimulated autophagy was demonstrated using various autophagic tests including GFP-LC3 puncta analysis, LC3II/LC3I gel shift and TEM observation. KEY FINDINGS: We discovered RB1CC1/FIP200 as cellular targets of miR-20a and miR-20b. Upon miR-20a and miR-20b overexpression, both mRNA and protein levels of RB1CC1/FIP200 decreased. miR-20a and miR-20b target sequences present in the 3' UTR of RB1CC1/FIP200 mRNAs and introduction of mutations abolished the miR-20a and miR-20b responsiveness. In MCF7 and MDA-MB 231 breast cancer cells, miR-20a and miR-20b over-expression attenuated basal and rapamycin-induced autophagy; while suppression of miR-20a or miR-20b by specific antagomir showed normal rapamycin-induced autophagic activity. SIGNIFICANCE: To our knowledge, this is the first study showing the significance of miR-20a and miR-20b regulating autophagy by targeting RB1CC1/FIP200. PMID- 26829384 TI - Characterization of parasite-specific indels and their proposed relevance for selective anthelminthic drug targeting. AB - Insertions and deletions (indels) are important sequence variants that are considered as phylogenetic markers that reflect evolutionary adaptations in different species. In an effort to systematically study indels specific to the phylum Nematoda and their structural impact on the proteins bearing them, we examined over 340,000 polypeptides from 21 nematode species spanning the phylum, compared them to non-nematodes and identified indels unique to nematode proteins in more than 3000 protein families. Examination of the amino acid composition revealed uneven usage of amino acids for insertions and deletions. The amino acid composition and cost, along with the secondary structure constitution of the indels, were analyzed in the context of their biological pathway associations. Species-specific indels could enable indel-based targeting for drug design in pathogens/parasites. Therefore, we screened the spatial locations of the indels in the parasite's protein 3D structures, determined the location of the indel and identified potential unique drug targeting sites. These indels could be confirmed by RNA-Seq data. Examples are presented illustrating the close proximity of some indels to established small-molecule binding pockets that can potentially facilitate selective targeting to the parasites and bypassing their host, thus reducing or eliminating the toxicity of the potential drugs. This study presents an approach for understanding the adaptation of pathogens/parasites at a molecular level, and outlines a strategy to identify such nematode-selective targets that remain essential to the organism. With further experimental characterization and validation, it opens a possible channel for the development of novel treatments with high target specificity, addressing both host toxicity and resistance concerns. PMID- 26829386 TI - Effect of ipragliflozin, an SGLT2 inhibitor, on progression of diabetic microvascular complications in spontaneously diabetic Torii fatty rats. AB - AIMS: We investigated the effect of the selective sodium-dependent glucose cotransporter 2 inhibitor ipragliflozin on the simultaneous progression of diabetic microvascular complications of retinopathy, nephropathy and neuropathy in individual Spontaneously Diabetic Torii (SDT) fatty rats. MAIN METHODS: Ipragliflozin was administered to male SDT fatty rats for 12weeks. Male Sprague Dawley rats of the same age were used as non-diabetic controls. Non-fasting plasma glucose and glycated hemoglobin levels were measured every 4weeks. Cataract formation was monitored once a week, and the electroretinogram was measured after 6weeks of treatment. After the treatment period, motor nerve conduction velocity was measured and urinalysis was conducted. Tissue samples were then dissected for histopathological examination. KEY FINDINGS: Treatment with ipragliflozin reduced glycated hemoglobin levels, inhibited the progression of cataract formation, prevented the prolongation of oscillatory potential peaks in the electroretinogram, ameliorated the slowing of motor nerve conduction velocity, and reduced the severity of glomerulosclerosis in SDT fatty rats. SIGNIFICANCE: These results suggest that the control of hyperglycemia with ipragliflozin slows the progression of the diabetic complications of retinopathy, nephropathy, and neuropathy. PMID- 26829387 TI - Evaluation of extraction methods for ochratoxin A detection in cocoa beans employing HPLC. AB - Cocoa is an important ingredient for the chocolate industry and for many food products. However, it is prone to contamination by ochratoxin A (OTA), which is highly toxic and potentially carcinogenic to humans. In this work, four different extraction methods were tested and compared based on their recoveries. The best protocol was established which involves an organic solvent-free extraction method for the detection of OTA in cocoa beans using 1% sodium hydrogen carbonate (NaHCO3) in water within 30 min. The extraction method is rapid (as compared with existing methods), simple, reliable and practical to perform without complex experimental set-ups. The cocoa samples were freshly extracted and cleaned-up using immunoaffinity column (IAC) for HPLC analysis using a fluorescence detector. Under the optimised condition, the limit of detection (LOD) and limit of quantification (LOQ) for OTA were 0.62 and 1.25 ng ml(-1) respectively in standard solutions. The method could successfully quantify OTA in naturally contaminated samples. Moreover, good recoveries of OTA were obtained up to 86.5% in artificially spiked cocoa samples, with a maximum relative standard deviation (RSD) of 2.7%. The proposed extraction method could determine OTA at the level 1.5 ug kg(-)(1), which surpassed the standards set by the European Union for cocoa (2 ug kg(-1)). In addition, an efficiency comparison of IAC and molecular imprinted polymer (MIP) column was also performed and evaluated. PMID- 26829388 TI - beta-Arrestin drives MAP kinase signalling from clathrin-coated structures after GPCR dissociation. AB - beta-Arrestins critically regulate G-protein-coupled receptor (GPCR) signalling, not only 'arresting' the G protein signal but also modulating endocytosis and initiating a discrete G-protein-independent signal through MAP kinase. Despite enormous recent progress towards understanding biophysical aspects of arrestin function, arrestin cell biology remains relatively poorly understood. Two key tenets underlie the prevailing current view: beta-arrestin accumulates in clathrin-coated structures (CCSs) exclusively in physical complex with its activating GPCR, and MAP kinase activation requires endocytosis of formed GPCR beta-arrestin complexes. We show here, using beta1-adrenergic receptors, that beta-arrestin-2 (arrestin 3) accumulates robustly in CCSs after dissociating from its activating GPCR and transduces the MAP kinase signal from CCSs. Moreover, inhibiting subsequent endocytosis of CCSs enhances the clathrin- and beta arrestin-dependent MAP kinase signal. These results demonstrate beta-arrestin 'activation at a distance', after dissociating from its activating GPCR, and signalling from CCSs. We propose a beta-arrestin signalling cycle that is catalytically activated by the GPCR and energetically coupled to the endocytic machinery. PMID- 26829390 TI - Correction to Hybrid Mesoporous Silica-Based Drug Carrier Nanostructures with Improved Degradability by Hydroxyapatite. PMID- 26829389 TI - DNA damage signalling targets the kinetochore to promote chromatin mobility. AB - In budding yeast, chromatin mobility increases after a DNA double-strand break (DSB). This increase is dependent on Mec1, the yeast ATR kinase, but the targets responsible for this phenomenon are unknown. Here we report that the Mec1 dependent phosphorylation of Cep3, a kinetochore component, is required to stimulate chromatin mobility after DNA breaks. Cep3 phosphorylation counteracts a constraint on chromosome movement imposed by the attachment of centromeres to the spindle pole body. A second constraint, imposed by the tethering of telomeres to the nuclear periphery, is also relieved after chromosome breakage. A non phosphorylatable Cep3 mutant that impairs DSB-induced chromatin mobility is proficient in DSB repair, suggesting that break-induced chromatin mobility may be dispensable for homology search. Rather, we propose that the relief of centromeric constraint promotes cell cycle arrest and faithful chromosome segregation through the engagement of the spindle assembly checkpoint. PMID- 26829391 TI - Associations between Cognition, Gender and Monocyte Activation among HIV Infected Individuals in Nigeria. AB - The potential role of gender in the occurrence of HIV-related neurocognitive impairment (NCI) and associations with markers of HIV-related immune activity has not been previously examined. In this study 149 antiretroviral-naive seropositive subjects in Nigeria (SP, 92 women and 57 men) and 58 seronegative (SN, 38 women and 20 men) were administered neuropsychological testing that assessed 7 ability domains. From the neuropsychological test scores was calculated a global deficit score (GDS), a measure of overall NCI. Percentages of circulating monocytes and plasma HIV RNA, soluble CD163 and soluble CD14 levels were also assessed. HIV SP women were found to be younger, more educated and had higher CD4+ T cell counts and borderline higher viral load measures than SP men. On the neuropsychological testing, SP women were more impaired in speed of information processing and verbal fluency and had a higher mean GDS than SN women. Compared to SP men, SP women were also more impaired in speed of information processing and verbal fluency as well as on tests of learning and memory. Numbers of circulating monocytes and plasma sCD14 and sCD163 levels were significantly higher for all SP versus all SN individuals and were also higher for SP women and for SP men versus their SN counterparts. Among SP women, soluble CD14 levels were slightly higher than for SP men, and SP women had higher viral load measurements and were more likely to have detectable virus than SP men. Higher sCD14 levels among SP women correlated with more severe global impairment, and higher viral load measurements correlated with higher monocyte numbers and sCD14 and sCD14 levels, associations that were not observed for SP men. These studies suggest that the risk of developing NCI differ for HIV infected women and men in Nigeria and, for women, may be linked to effects from higher plasma levels of HIV driving activation of circulating monocytes. PMID- 26829392 TI - Variation in chemical composition and physical characteristics of cereal grains from different genotypes. AB - Genotypes of cereal grains, including winter barley (n = 21), maize (n = 27), oats (n = 14), winter rye (n = 22), winter triticale (n = 21) and winter wheat (n = 29), were assayed for their chemical composition and physical characteristics as part of the collaborative research project referred to as GrainUp. Genotypes of one grain species were grown on the same site, except maize. In general, concentrations of proximate nutrients were not largely different from feed tables. The coefficient of variation (CV) for the ether extract concentration of maize was high because the data pool comprised speciality maize bred for its high oil content. A subset of 8 barley, 20 rye, 20 triticale and 20 wheat samples was analysed to differ significantly in several carbohydrate fractions. Gross energy concentration of cereal grains could be predicted from proximate nutrient concentration with good accuracy. The mean lysine concentration of protein was the highest in oats (4.2 g/16 g N) and the lowest in wheat (2.7 g/16 g N). Significant differences were also detected in the concentrations of macro elements as well as iron, manganese, zinc and copper. Concentrations of arsenic, cadmium and lead were below the limit of detection. The concentration of lower inositol phosphates was low, but some inositol pentaphosphates were detected in all grains. In barley, relatively high inositol tetraphosphate concentration also was found. Intrinsic phytase activity was the highest in rye, followed by triticale, wheat, barley and maize, and it was not detectable in oats. Substantial differences were seen in the thousand seed weight, test weight, falling number and extract viscoelasticity characteristics. The study is a comprehensive overview of the composition of different cereal grain genotypes when grown on the same location. The relevance of the variation in composition for digestibility in different animal species will be subject of other communications. PMID- 26829393 TI - Role of Platelet Parameters on Sudden Sensorineural Hearing Loss: A Case-Control Study in Iran. AB - Sudden sensorineural hearing loss (SSNHL) is a common otological disorder characterized by a hearing loss greater than 30 dB over three consecutive frequencies, in less than 72 hours. It has been established that platelet parameters, such as mean platelet volume, are associated with ischemic heart events, whose clinical manifestations are similar to those of SSNHL. Hence, we aimed to determine if the platelet count, mean platelet volume and platelet distribution width are related to the occurrence and severity of sudden sensorineural hearing loss. A case-control prospective study was conducted in a teaching hospital in Iran. One hundred-eight patients with SSNHL and an equal number of healthy, age- and sex-matched controls were enrolled in the study. Peripheral venous blood samples were collected from the subjects, and the platelet count, mean platelet volume and platelet distribution width were measured with an automated blood cell counter. Analysis of the audiometry and hematological test results using SPSS22 software showed no statistical correlation between the platelet parameters and the occurrence of SSNHL, but correlation coefficients showed a significant correlation between PDW and hearing loss severity in patients group. However, further investigation is required to unequivocally establish the absence of correlation between the platelet parameters and occurrence of SSNHL. PMID- 26829394 TI - Androgen Receptor Genotype in Humans and Susceptibility to Endocrine Disruptors. AB - Although animal studies have raised concern that the influence of endocrine disrupting compounds would obstruct the development of the male reproductive system, in general, exposure levels far above those found in humans have been needed to induce reproductive toxicity in animal models. Human data are inconclusive and have evoked the question whether endocrine-disrupting compounds can have any impact on hormonal function and thus health consequences when natural hormones are present. Indeed, many contaminants with hormone-like activity are much less potent than endogenous hormones themselves: 17beta oestradiol was, for instance, estimated to be 17,000 times more potent than o,p' DDT. However, humans are exposed to a multitude of agents, and when present in sufficient number and concentration, they might in principle act collected on the actions of endogenous hormones. Whether such effects will be physiologically relevant is still not known. Nevertheless, in the worst-case scenario, there are no threshold levels below which there are no effects at all, and one target molecule is the androgen receptor. This mini review focuses on the androgen receptor gene, its link with classical endocrine disruptors and smoking, and how common genetic variants in the androgen receptor gene may influence physiological outcomes. PMID- 26829395 TI - Psychological functioning among vertically infected HIV-positive children and their primary caregivers. AB - The current study sought to explore the association between primary caregiver depressive symptoms and the psychological functioning in children vertically infected with human immunodeficiency virus (HIV) living in Eastern Cape, South Africa. A cross-sectional data were collected using the Beck Depression Inventory and Strength and Difficulties Questionnaire in a sample of 152 caregiver/child dyads. The results revealed that poorer psychological functioning in children was significantly associated with depressive symptoms in caregivers. This relationship existed whether or not the child was raised by a biological or non biological caregiver as well as for both genders. Younger children's psychological functioning was more negatively influenced than that of older children raised by a caregiver with depressive symptoms. In the context of a large treatment gap for common mental disorders in South Africa, there is a need for interventions to address maternal mental health in families infected and affected by the HIV/AIDS pandemic as a mental health promotion strategy given that HIV-infected children are a particularly vulnerable population for poor mental and behavioural health outcomes. PMID- 26829396 TI - Toward Understanding the Catalytic Mechanism of Human Paraoxonase 1: Site Specific Mutagenesis at Position 192. AB - Human paraoxonase 1 (h-PON1) is a serum enzyme that can hydrolyze a variety of substrates. The enzyme exhibits anti-inflammatory, anti-oxidative, anti atherogenic, anti-diabetic, anti-microbial and organophosphate-hydrolyzing activities. Thus, h-PON1 is a strong candidate for the development of therapeutic intervention against a variety conditions in human. However, the crystal structure of h-PON1 is not solved and the molecular details of how the enzyme hydrolyzes different substrates are not clear yet. Understanding the catalytic mechanism(s) of h-PON1 is important in developing the enzyme for therapeutic use. Literature suggests that R/Q polymorphism at position 192 in h-PON1 dramatically modulates the substrate specificity of the enzyme. In order to understand the role of the amino acid residue at position 192 of h-PON1 in its various hydrolytic activities, site-specific mutagenesis at position 192 was done in this study. The mutant enzymes were produced using Escherichia coli expression system and their hydrolytic activities were compared against a panel of substrates. Molecular dynamics simulation studies were employed on selected recombinant h PON1 (rh-PON1) mutants to understand the effect of amino acid substitutions at position 192 on the structural features of the active site of the enzyme. Our results suggest that, depending on the type of substrate, presence of a particular amino acid residue at position 192 differentially alters the micro environment of the active site of the enzyme resulting in the engagement of different subsets of amino acid residues in the binding and the processing of substrates. The result advances our understanding of the catalytic mechanism of h PON1. PMID- 26829398 TI - Correction: Extraction and Identification of the Pigment in the Adductor Muscle Scar of Pacific Oyster Crassostrea gigas. PMID- 26829397 TI - Proteomics Study on Nonallergic Hypersensitivity Induced by Compound 4880 and Ovalbumin. AB - Nonallergic hypersensitivity reaction (NHR) accounts for more than 77% of all immune-mediated immediate hypersensitivity reactions and has become a serious threat to public health. Here, proteomics was used to study the NHR mechanism of two typical substances, the compound 4880 and ovalbumin. Twelve different proteins were suggested as potential biomarkers for examining the NHR mechanism, and our results revealed that the mechanism mainly encompassed 2 processes, i.e., generation and effect processes. The generation process could be classified as direct stimulation, complement (classical and alternative), coagulation, kallikrein-kinin, and integrated pathways. Thus glutathione peroxidase 1, terminal complement complex (complement factor 4d and Bb), coagulation 13, kininogen-1, and IgE could be used as candidate biomarkers for the indication of the corresponding pathways respectively, the proteins were further confirmed by ELISA. And the effect process was mainly composed of histamine as well as proteins such as DCD and MYLPF, which could be used as important indices for the symptoms of NHR. Our study differs from previous studies in that C4880 was found to not only be involved in the direct stimulation pathway, but also in the activated complement and kallikrein-kinin pathways through the coagulation pathway. We also report for the first time that ovalbumin-induced NHR could be a combination of the coagulation, classical complement, and integrated pathways. PMID- 26829399 TI - Disease Risk Perception and Safety Practices: A Survey of Australian Flying Fox Rehabilitators. AB - Interactions with flying foxes pose disease transmission risks to volunteer rehabilitators (carers) who treat injured, ill, and orphaned bats. In particular, Australian bat lyssavirus (ABLV) can be transmitted directly from flying foxes to humans in Australia. Personal protective equipment (PPE) and rabies vaccination can be used to protect against lyssavirus infection. During May and June 2014, active Australian flying fox carers participated in an online survey (SOAR: Survey Of Australian flying fox Rehabilitators) designed to gather demographic data, assess perceptions of disease risk, and explore safety practices. Responses to open-ended questions were analysed thematically. A logistic regression was performed to assess whether rehabilitators' gender, use of PPE, threat perception, and years of experience predicted variation in their odds of being bitten or scratched. Eligible responses were received from 122 rehabilitators located predominantly on the eastern coast of Australia. Eighty-four percent of respondents were female. Years of experience ranged from <1 to 30 years (median 5 years). Respondents were highly educated. All rehabilitators were vaccinated against rabies and 94% received a rabies titre check at least every two years. Sixty-three percent of carers did not perceive viruses in flying foxes as a potential threat to their health, yet 74% of carers reported using PPE when handling flying foxes. Eighty-three percent of rehabilitators had received a flying fox bite or scratch at some point during their career. Carers provide an important community service by rescuing and rehabilitating flying foxes. While rehabilitators in this study have many excellent safety practices, including a 100% vaccination rate against rabies, there is room for improvement in PPE use. We recommend 1) the establishment of an Australia-wide set of guidelines for safety when caring for bats and 2) that the responsible government agencies in Australia support carers who rescue potentially ABLV-infected bats by offering compensation for PPE. PMID- 26829400 TI - Utility of histogram analysis of ADC maps for differentiating orbital tumors. AB - PURPOSE: We aimed to evaluate the role of histogram analysis of apparent diffusion coefficient (ADC) maps for differentiating benign and malignant orbital tumors. METHODS: Fifty-two patients with orbital tumors were enrolled from March 2013 to November 2014. Pretreatment diffusion-weighted imaging was performed on a 3T magnetic resonance scanner with b factors of 0 and 800 s/mm2, and the corresponding ADC maps were generated. Whole-tumor regions of interest were drawn on all slices of the ADC maps to obtain histogram parameters, including ADCmean, ADCmedian, standard deviation (SD), skewness, kurtosis, quartile, ADC10, ADC25, ADC75, and ADC90. Histogram parameter differences between benign and malignant orbital tumors were compared. The diagnostic value of each significant parameter in predicting malignant tumors was established. RESULTS: Age, ADCmean, ADCmedian, quartile, kurtosis, ADC10, ADC25, ADC75, and ADC90 parameters were significantly different between benign and malignant orbital tumor groups, while gender, location, SD, and skewness were not significantly different. The best diagnostic performance in predicting malignant orbital tumors was achieved at the threshold of ADC10=0.990 (AUC, 0.997; sensitivity, 96.2%; specificity, 100%). CONCLUSION: Histogram analysis of ADC maps holds promise for differentiating benign and malignant orbital tumors. ADC10 has the potential to be the most significant parameter for predicting malignant orbital tumors. PMID- 26829402 TI - Meta-analysis of quality of life in children and adolescents with ADHD: By both parent proxy-report and child self-report using PedsQLTM. AB - Attention deficit hyperactivity disorder (ADHD) is a prevalent developmental disorder that seriously and negatively impacts a child's health-related quality of life (HRQOL). However, no meta-analysis has been conducted to examine the magnitude of impact, domains affected and factors moderating the impact. This review included nine studies that compared HRQOL of children or adolescents with ADHD with those with typical development using both child self-reports and parent proxy-reports. Seven among nine studies were meta-analytically synthesized to examine the degree of impact of ADHD on children and adolescents, parent-child discrepancy, and the moderators. The results indicate that ADHD impact a child's or adolescent's HRQOL negatively with a moderate effect in physical and a severe effect in psychosocial (i.e., emotional, social, and school) domains. Parental ratings of overall HRQOL in children or adolescents with ADHD were not significantly different from child's ratings when compared with typically developing children and adolescents. Age was negatively associated with all domains of HRQOL in children and adolescents with ADHD both by parent- and child ratings, and the strongest effect was found in parental ratings of child's emotional HRQOL, with a moderate correlation. This meta-analysis suggests that HRQOL may be assessed in children and adolescents with ADHD both by parent proxy- and child self-reports, and that interventions may be planned accordingly. Future meta-analysis may explore how measures of HRQOL and other factors including child, parental, familiar and school characteristics influence the impact of ADHD and the parent-child agreement in children and adolescents. PMID- 26829403 TI - Iterative Approximation of Basic Belief Assignment Based on Distance of Evidence. AB - In the theory of belief functions, the approximation of a basic belief assignment (BBA) is for reducing the high computational cost especially when large number of focal elements are available. In traditional BBA approximation approaches, a focal element's own characteristics such as the mass assignment and the cardinality, are usually used separately or jointly as criteria for the removal of focal elements. Besides the computational cost, the distance between the original BBA and the approximated one is also concerned, which represents the loss of information in BBA approximation. In this paper, an iterative approximation approach is proposed based on maximizing the closeness, i.e., minimizing the distance between the approximated BBA in current iteration and the BBA obtained in the previous iteration, where one focal element is removed in each iteration. The iteration stops when the desired number of focal elements is reached. The performance evaluation approaches for BBA approximations are also discussed and used to compare and evaluate traditional BBA approximations and the newly proposed one in this paper, which include traditional time-based way, closeness-based way and new proposed ones. Experimental results and related analyses are provided to show the rationality and efficiency of our proposed new BBA approximation. PMID- 26829401 TI - Broad and potent antiviral activity of the NAE inhibitor MLN4924. AB - In terms of infected human individuals, herpesviruses range among the most successful virus families. Subclinical herpesviral infections in healthy individuals contrast with life-threatening syndromes under immunocompromising and immunoimmature conditions. Based on our finding that cytomegaloviruses interact with Cullin Roc ubiquitin ligases (CRLs) in the context of interferon antagonism, we systematically assessed viral dependency on CRLs by utilizing the drug MLN4924. CRL activity is regulated through the conjugation of Cullins with the ubiquitin-like molecule Nedd8. By inhibiting the Nedd8-activating Enzyme (NAE), MLN4924 interferes with Nedd8 conjugation and CRL activity. MLN4924 exhibited pronounced antiviral activity against mouse and human cytomegalovirus, herpes simplex virus (HSV)- 1 (including multi-drug resistant clinical isolates), HSV-2, adeno and influenza viruses. Human cytomegalovirus genome amplification was blocked at nanomolar MLN4924 concentrations. Global proteome analyses revealed that MLN4924 blocks cytomegaloviral replication despite increased IE1 amounts. Expression of dominant negative Cullins assigned this IE regulation to defined Cullin molecules and phenocopied the antiviral effect of MLN4924. PMID- 26829404 TI - Synthesis of N-Sulfonyl Arylaldimines Developed by Retesting an Old Process. AB - By simply heating the mixture of an arylaldehyde and a sulfonylisocyanate in a solvent or in neat form under catalyst- and additive-free conditions, the desired N-sulfonylimine was produced with the release of carbon dioxide. The method is characterized by its unique clean efficiency, convenience, and scalability, but it was reported to fail half a century ago. PMID- 26829405 TI - Deficient visuospatial working memory functions and neural correlates of the default-mode network in adolescents with autism spectrum disorder. AB - In addition to the essential features of autism spectrum disorder (ASD), namely social communication deficits and repetitive behaviors, individuals with ASD may suffer from working memory deficits and an altered default-mode network (DMN). We hypothesized that an altered DMN is related to working memory deficits in those with ASD. A total of 37 adolescents with ASD and 36 age- and IQ-matched typically developing (TD) controls were analyzed. Visuospatial working memory performance was assessed using pattern recognition memory (PRM), spatial recognition memory (SRM), and paired-associates learning (PAL) tasks. The intrinsic functional connectivity (iFC) of the DMN was indexed by the temporal correlations between the resting-state functional magnetic resonance imaging signals of pairs of DMN regions, including those between the posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC) and between the PCC and parahippocampi (PHG). The corresponding structural connectivity of the DMN was indexed by the generalized fractional anisotropy (GFA) of the dorsal and ventral cingulum bundles on the basis of diffusion spectrum imaging data. The results showed that ASD adolescents exhibited delayed correct responses in PRM and SRM tasks and committed more errors in the PAL task than the TD controls did. The delayed responses during the PRM and SRM tasks were negatively correlated with bilateral PCC-mPFC iFCs, and PAL performance was negatively correlated with right PCC-PHG iFC in ASD adolescents. Furthermore, ASD adolescents showed significant lower GFA in the right cingulum bundles than the TD group did; the GFA value was negatively correlated with SRM performance in ASD. Our results provide empirical evidence for deficient visuospatial working memory and corresponding neural correlates within the DMN in adolescents with ASD. Autism Res 2016, 9: 1058-1072. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 26829406 TI - Determination of 1,4-Dioxane in the Cape Fear River Watershed by Heated Purge-and Trap Preconcentration and Gas Chromatography-Mass Spectrometry. AB - Recent U.S. Environmental Protection Agency data show that 1,4-dioxane is frequently detected in U.S. drinking water derived from both groundwater and surface water. 1,4-Dioxane is a likely human carcinogen, and an excess 10(-6) cancer risk is associated with a drinking water concentration of 0.35 MUg/L. To support 1,4-dioxane occurrence investigations, source identification and exposure assessment, a rapid and sensitive analytical method capable of quantifying 1,4 dioxane over a wide concentration range in a broad spectrum of aqueous matrices was developed. The fully automated method is based on heated purge-and-trap preconcentration and gas chromatography/mass spectrometry with selected-ion storage and has a reporting limit of 0.15 MUg/L. Quantification of 1,4-dioxane was accomplished by isotope dilution using mass-labeled 1,4-dioxane-d8 as internal standard. Matrix spikes yielded recoveries of 86-115% in drinking water, groundwater, surface water, and wastewater treatment plant (WWTP) effluent. Also, 1,3-dioxane can be distinguished from 1,4-dioxane. The method was applied to investigate 1,4-dioxane occurrence and sources in the Cape Fear River watershed of North Carolina. 1,4-Dioxane concentrations ranged from <0.15 MUg/L in nonimpacted surface water to 436 MUg/L downstream of a WWTP discharge. In WWTP effluent, 1,4-dioxane concentrations varied widely, with a range of 1.3-2.7 MUg/L in one community and 105-1,405 MUg/L in another. Discharges from three municipal WWTPs were primarily responsible for elevated 1,4-dioxane concentrations in the Cape Fear River watershed. PMID- 26829407 TI - Triple Disease Combination: Familial Mediterranean Fever, Crohn's Disease, and Chronic Idiopathic Urticaria with Angioedema. PMID- 26829408 TI - Low Fecal Calprotectin Correlates with Histological Remission and Mucosal Healing in Ulcerative Colitis and Colonic Crohn's Disease. AB - BACKGROUND: Data regarding the correlation of histologic and endoscopic healing with fecal calprotectin (FC) are conflicting. We examined how FC levels correlate with histological and endoscopic remission in colonic inflammatory bowel disease. METHODS: Fifty-eight patients (23 with colonic Crohn's disease [CD] and 35 with ulcerative colitis [UC]) were included. Clinical activity was assessed by Harvey Bradshaw index (CD) and Mayo score (UC). Inflammatory activity was assessed by ileocolonoscopy, C-reactive protein, and FC. Clinical remission was defined as Harvey-Bradshaw index <= 4 or Mayo score <= 2 and mucosal healing as Mayo endoscopic subscore = 0 (UC), and Simple Endoscopic Score-CD <3 (CD). Histologic activity was assessed in 27 patients (15 CD, 12 UC). Histological remission was defined as absence of active inflammation (Geboes score <3.1) and absence of basal plasmacytosis. RESULTS: In UC, FC correlated with clinical Mayo score (r = 0.63, P < 0.0001). This correlation was strengthened by adding the endoscopic subscore (r = 0.90, P < 0.0001). The endoscopic subscore also independently correlated with FC (r = 0.96, P < 0.0001). In Crohn's colitis, endoscopic activity correlated with FC (r = 0.61, P < 0.001). FC levels were lower overall for patients with endoscopic remission compared with active endoscopic disease (median 100 versus 1180 MUg/g, P < 0.0001). FC also correlated with histological remission (Geboes score < 3.1) and absence of basal plasmacytosis in CD (r = 0.77, r = 0.80, respectively; P < 0.01). Area under the curve for FC as a predictor of histological remission (Geboes score <3.1) was 0.95 (95% CI, 0.82 1). CONCLUSIONS: Low FC correlates well with histological remission and mucosal healing in colonic inflammatory bowel disease and is thus a clinically useful surrogate for inflammatory activity. PMID- 26829409 TI - Does Crohn's Disease with Concomitant Orofacial Granulomatosis Represent a Distinctive Disease Subtype? AB - BACKGROUND: Although orofacial granulomatosis (OFG) may present as a separate clinical entity, it often seems in conjunction with various systemic diseases, of which Crohn's disease (CD) is one of the most common. The aim of this study was to investigate whether CD with concomitant OFG represents a distinctive disease subtype. METHODS: Twenty-one patients with CD and concomitant OFG (CD+OFG group) were included in the study. As the reference group, a cohort of 39 patients with CD but without OFG (CD-R group) was used. Demographic data and clinical characteristics were recorded at the time of diagnosis. The 2 groups were compared using multivariate analyses. RESULTS: The percentage of patients with intestinal inflammation in the upper gastrointestinal tract was significantly higher in the CD+OFG group, as compared with the CD-R group (81% versus 33%; P < 0.001). Furthermore, ileocolonic inflammation was significantly more common in the CD+OFG patients (81% versus 46%; P = 0.013). In addition, perianal disease was more frequently observed in the CD+OFG group (48% versus 18%; P = 0.033). Significantly more patients showed evidence of granulomas in the primary endoscopy in the CD+OFG group than in the CD-R group (81% versus 38%; P = 0.003). CONCLUSION: The data from this study suggest that the presence of CD in conjunction with OFG represents a distinctive subphenotype of CD that is characterized by extensive inflammation, perianal disease, and pronounced granuloma formation in the intestine. PMID- 26829410 TI - Risk Factors and Clinical Outcomes Associated with Cytomegalovirus Colitis in Patients with Acute Severe Ulcerative Colitis. AB - BACKGROUND: Cytomegalovirus (CMV) colitis can contribute to an unfavorable outcome of acute severe ulcerative colitis (ASUC). The purpose of this study was to evaluate the clinical outcomes of ASUC according to the CMV status and identify risk factors for CMV colitis in patients with ASUC. METHODS: We retrospectively analyzed patients with ASUC from 2011 to 2014 according to the criteria of Truelove and Witts. CMV colitis was diagnosed by histopathological and/or immunohistochemical analysis of tissue samples. The risk factors for CMV colitis were investigated and clinical outcomes were assessed using the rate of rescue therapy and colectomy. RESULTS: Of 149 patients with ASUC, 50 (33.6%) were diagnosed with CMV colitis. During admission, 16 of 149 patients (10.7%) underwent colectomy: 7 of 50 (14.0%) in the ASUC-CMV group versus 9 of 99 (9.1%) in the ASUC-only group (P = 0.364). The need for rescue therapy was 2.28-fold higher in the ASUC-CMV group than in the ASUC-only group in multivariate analysis (95% confidence interval, 1.10-4.72). Multivariate analysis also revealed that recent use of high-dose steroids (odds ratio, 3.30; 95% confidence interval, 1.33 8.19) and a higher Mayo score (odds ratio, 1.58; 95% confidence interval, 1.05 2.38) were risk factors for CMV colitis. CONCLUSIONS: CMV colitis often occurs in ASUC, particularly in patients who have recently been treated with high-dose steroids and have a higher Mayo score on admission. Patients with ASUC and CMV colitis seem to have a poorer prognosis, as indicated by the greater need for rescue therapy. PMID- 26829411 TI - The Maxillary Sinus Floor Elevation Using a Poly-L-Lactic Acid Device to Create Space Without Bone Graft: Case Series Study of Five Patients. AB - Maxillary sinus floor elevation using autologous or alloplastic bone grafting is often performed for implant treatment of maxillary molars; however, issues related to the donor site and complications such as infection have been reported. We performed maxillary sinus floor elevation using poly-L-lactic acid (PLLA) as a space-making material in patients with an insufficient bone mass (<3 mm) for simultaneous implantation between the alveolar crest and floor of the maxillary sinus and evaluated the newly formed bone. Conventional antrostomy of the maxillary sinus from the lateral wall was performed, and PLLA was placed on the floor of the maxillary sinus after elevating the sinus membrane. Six months after surgery, the bone mass and density were measured using quantitative computed tomography, and histological evaluation was performed. No complications were recorded. Radiological findings showed a bone-like radiopaque appearance, and histological examination revealed new bone formation in all patients. In cases with insufficient bone mass prior to simultaneous implant placement, this method of maxillary sinus augmentation allows for sufficient bone augmentation without bone grafting. PMID- 26829412 TI - Cardiac arrest with vagal stimulation during intraoperative nerve monitoring. AB - BACKGROUND: Intraoperative neuromonitoring (IONM) is widely used during thyroid surgery. During both intermittent and continuous IONM stimulation of the vagus nerve is performed. This has previously been reported to be safe. METHODS: We present our findings based on the case reports of 2 patients. RESULTS: IONM of the recurrent laryngeal nerve (RLN), following the standards of the International Neuromonitoring Study Group, was conducted in 2 patients, one undergoing thyroid surgery and the second parathyroid surgery. In both cases, after dissection and stimulation of the vagus nerve on 1 mAmp, the patients became asystolic. Resuscitation efforts were successful in both patients. CONCLUSION: These 2 cases demonstrate that stimulation of the vagus nerve during IONM can lead to profound cardiac events. Consideration should be given to these potential complications when utilizing IONM. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2419-E2420, 2016. PMID- 26829413 TI - 29th Congress of the Italian Society of Neonatology - Lombardy section | Bergamo, 29-30 January 2016. AB - This abstract book contains the abstracts presented at the 29th Congress of the Italian Society of Neonatology - Lombardy section | Bergamo, 29-30 January 2016. PMID- 26829414 TI - Light-mediated modulation of helix angle and rate of seminal root tip movement determines root morphology of young rice seedlings. AB - Seminal root growth is one of the factors to determine rice seedling establishment. Our previous reports showed light can induce Z-type wavy root and coiling root morphology in several rice (Oryza sativa L.) varieties, and the regulated Z-type and unregulated coil seminal roots were resulted by different circumnutational trajectories. Moreover, the light-induced seminal root waving was conducted by an NO-dependent signaling pathway. In order to further reveal the difference of root tip movement between straight and wavy seminal roots; here, the root tip movement trajectories of Tainung 67 variety (TNG67; presented straight root in light conditions) and Taichung Native 1 (TCN1; presented Z-type wavy root in light) were recorded and analyzed in both white light and dark (dim far-red light was applied in dark for taking time-lapse photography) conditions. The results showed the root tip movement of both rice varieties in low intensity of dim far-red light conditions were followed the circumnutation path. However, the stimuli of high intensity of white light would increase the root helix angle in TCN1 seedlings but not in TNG67. In addition, slowing down the rate of root helix was induced by white light treatment in TCN1 but not in TNG67 seedlings. In conclusion, changes of TCN1 rice seminal root morphology from straight to wavy type stimulated by light was resulted by both helix angle increasing and circumnutation rate slowing of root tip movement. PMID- 26829416 TI - Chronic Obstructive Pulmonary Disease and Stroke. Strange Bedfellows. PMID- 26829415 TI - Impact of Mandatory HIV Screening in the Emergency Department: A Queuing Study. AB - To improve HIV screening rates, New York State in 2010 mandated that all persons 13-64 years receiving health care services, including care in emergency departments (EDs), be offered HIV testing. Little attention has been paid to the effect of screening on patient flow. Time-stamped ED visit data from patients eligible for HIV screening, 7,844 of whom were seen by providers and 767 who left before being seen by providers, were retrieved from electronic health records in one adult ED. During day shifts, 10% of patients left without being seen, and during evening shifts, 5% left without being seen. All patients seen by providers were offered testing, and 6% were tested for HIV. Queuing models were developed to evaluate the effect of HIV screening on ED length of stay, patient waiting time, and rate of leaving without being seen. Base case analysis was conducted using actual testing rates, and sensitivity analyses were conducted to evaluate the impact of increasing the testing rate. Length of ED stay of patients who received HIV tests was 24 minutes longer on day shifts and 104 minutes longer on evening shifts than for patients not tested for HIV. Increases in HIV testing rate were estimated to increase waiting time for all patients, including those who left without being seen. Our simulation suggested that incorporating HIV testing into ED patient visits not only adds to practitioner workload but also increases patient waiting time significantly during busy shifts, which may increase the rate of leaving without being seen. PMID- 26829417 TI - The Global Epidemiology of Sepsis. Does It Matter That We Know So Little? PMID- 26829418 TI - Apneic Oxygenation for Intubation in the Critically Ill. Let's Not Give Up! PMID- 26829419 TI - Treating Acute Kidney Injury. One Less Weapon in the Armamentarium? PMID- 26829420 TI - Gene Therapy with Adeno-associated Virus for Cystic Fibrosis. PMID- 26829421 TI - Dyspnea Intensity: A Patient-reported Measure of Respiratory Drive and Disease Severity. PMID- 26829422 TI - Is Continuous Positive Airway Pressure an Effective and Practical Antihypertensive Agent? PMID- 26829423 TI - "We Understand the Prognosis, but We Live with Our Heads in the Clouds": Understanding Patient and Family Outcome Expectations and Their Influence on Shared Decision Making. PMID- 26829424 TI - Liver Dysfunction Is Associated with Long-Term Mortality in Septic Shock. PMID- 26829425 TI - Delamanid and Bedaquiline Resistance in Mycobacterium tuberculosis Ancestral Beijing Genotype Causing Extensively Drug-Resistant Tuberculosis in a Tibetan Refugee. PMID- 26829426 TI - An Important Step Forward, but Still a Way to Go. PMID- 26829427 TI - Idiopathic Pulmonary Fibrosis and Prothrombotic State. PMID- 26829428 TI - Reply to "An Important Step Forward, but Still a Way to Go". PMID- 26829429 TI - Reply to "An Important Step Forward, but Still a Way to Go" and "Idiopathic Pulmonary Fibrosis and Prothrombotic State". PMID- 26829430 TI - Retraction: Decline in NRF2-regulated Antioxidants in Chronic Obstructive Pulmonary Disease Lungs Due to Loss of Its Positive Regulator, DJ-1; Heightened Endoplasmic Reticulum Stress in the Lungs of Patients with Chronic Obstructive Pulmonary Disease: The Role of Nrf2-Regulated Proteasomal Activity. PMID- 26829431 TI - Assessing the risk factors for difficult-to-treat depression and treatment resistant depression. AB - Depression is the leading cause of disability among people across the globe, according to the World Health Organization. Among those who have been diagnosed, many fail to achieve remission after following recommended antidepressant medication and psychosocial therapies. In particular, difficult-to-treat and treatment-resistant depression may cause severe impairments for patients, including diminished cognitive functioning, increased medical bills, and decreased workplace performance, as well as an increased risk of developing comorbid illnesses. However, many tools are available to clinicians for identifying treatment-resistant depression, including rating scales such as the 9 question Patient Health Questionnaire (PHQ-9) and the Quick Inventory of Depressive Symptomatology (QIDS-SR16), as well as clinical evidence related to risk factors for difficult-to-treat or treatment-resistant depression. Accurately identifying treatment-resistant depression is the first step toward changing treatment regimens to help patients achieve remission. PMID- 26829432 TI - Implementing treatment strategies for different types of depression. AB - Diagnosing and treating major depressive disorder (MDD) accurately and efficiently is challenging for many clinicians. Recent additions to the Diagnostic and Statistical Manual of Mental Disorders (DSM) as well as potential moderators of antidepressant response such as pretreatment phenomenological characteristics (eg, body mass index, drug metabolism markers) may help physicians to better stratify patients and make informed decisions on the best course of treatment to obtain remission. The evidence base suggests that combining traditional antidepressant therapy with atypical antipsychotics may increase the chance for remission. Other strategies that may help include switching to another antidepressant as monotherapy or combining lithium, thyroid hormone, or psychotherapy. Moreover, in some cases, a manualized-based psychotherapeutic approach may be an appropriate first-line or alternative treatment avenue for adults with MDD. PMID- 26829433 TI - Identifying patients with depression who require a change in treatment and implementing that change. AB - Creating an effective treatment regimen for patients diagnosed with major depressive disorder (MDD) can be a challenge for clinicians. With each treatment trial, only 20% to 30% of patients achieve remission, and many of those who do reach remission experience residual symptoms. Patients with treatment-resistant depression or with residual symptoms are candidates for a change in treatment. Other patients requiring treatment changes are those who experience intolerable adverse effects and those who experience an illness recurrence. Because early detection can lead to improved outcomes, clinicians must be vigilant about assessing patients to identify when one or more of these situations occur. Clinicians must also communicate effectively with their patients to ensure that they understand the treatment strategies, goals, and potential adverse effects; have realistic expectations of treatment; and express their treatment preferences. Timely and appropriate treatment adjustment is necessary to help patients with MDD achieve recovery. PMID- 26829434 TI - Managing medical comorbidities in patients with depression to improve prognosis. AB - Medical comorbidities contribute to poor antidepressant response, treatment resistance, and poor outcomes in many patients with depression. Depression can co occur with thyroid conditions, chronic pain conditions, central nervous system disorders, and more. Inflammatory conditions such as diabetes and obesity are also associated with depression, and the connection between inflammation and depression may lead to testing that could better match patients to specific antidepressant treatment. Interventions for patients with depression and a comorbid medical condition include careful selection of antidepressant therapy as well as psychotherapy and adjunctive agents. PMID- 26829435 TI - An Uncommon Cause of Recurrent Venous Thromboembolism. PMID- 26829436 TI - Recognizing Quality Improvement and Patient Safety Activities in Academic Promotion in Departments of Medicine: Innovative Language in Promotion Criteria. PMID- 26829437 TI - A Break in the Wall: Stercoral Colitis. PMID- 26829438 TI - Examining the Reading Level of Internet Medical Information for Common Internal Medicine Diagnoses. AB - BACKGROUND: The National Institutes of Health (NIH) recommend that health materials be written at a grade 6-7 reading level, which has generally not been achieved in online reading materials. Up to the present time, there have not been any assessments focused on the reading level of online educational materials across the most popular consumer Web sites for common internal medicine diagnoses. In this study, we examined the readability of open-access online health information for 9 common internal medicine diagnoses. METHODS: Nine of the most frequently encountered inpatient and ambulatory internal medicine diagnoses were selected for analysis. In November and December 2014, these diagnoses were used as search terms in Google, and the top 5 Web sites across all diagnoses and a diagnosis-specific site were analyzed across 5 validated reading indices. RESULTS: On average, the lowest reading grade-level content was provided by the NIH (10.7), followed by WebMD (10.9), Mayo Clinic (11.3), and diagnosis-specific Web sites (11.5). Conversely, Wikipedia provided content that required the highest grade-level readability (14.6). The diagnoses with the lowest reading grade levels were chronic obstructive pulmonary disease (10.8), followed by diabetes (10.9), congestive heart failure (11.7), osteoporosis (11.7) and hypertension (11.7). Depression had the highest grade-level readability (13.8). DISCUSSION: Despite recommendations for patient health information to be written at a grade 6-7 reading level, our examination of online educational materials pertaining to 9 common internal medicine diagnoses revealed reading levels significantly above the NIH recommendation. This was seen across both diagnosis specific and general Web sites. There is a need to improve the readability of online educational materials made available to patients. These improvements have the potential to greatly enhance patient awareness, engagement, and physician patient communication. PMID- 26829439 TI - Density Functional Theory Calculation of the Band Alignment of (1010) In(x)Ga(1 x)N/Water Interfaces. AB - Conduction band edge (CBE) and valence band edge (VBE) positions of InxGa1-xN photoelectrodes were computed using density functional theory methods. The band edges of fully solvated GaN and InN model systems were aligned with respect to the standard hydrogen electrode using a molecular dynamics hydrogen electrode scheme applied earlier to TiO2/water interfaces. Similar to the findings for TiO2, we found that the Purdew-Burke-Ernzerhof (PBE) functional gives a VBE potential which is too negative by 1 V. This cathodic bias is largely corrected by application of the Heyd-Scuseria-Ernzerhof (HSE06) hybrid functional containing a fraction of Hartree-Fock exchange. The effect of a change of composition was investigated using simplified model systems consisting of vacuum slabs covered on both sides by one monolayer of H2O. The CBE was found to vary linearly with In content. The VBE, in comparison, is much less sensitive to composition. The data show that the band edges straddle the hydrogen and oxygen evolution potentials for In fractions less than 47%. The band gap was found to exceed 2 eV for an In fraction less than 54%. PMID- 26829441 TI - Impaired Insulin Suppression of VLDL-Triglyceride Kinetics in Nonalcoholic Fatty Liver Disease. AB - CONTEXT: Nonalcoholic fatty liver disease (NAFLD) is associated with glucose and lipid metabolic abnormalities. However, insulin suppression of very low-density lipoprotein-triglyceride (VLDL-TG) kinetics is not fully understood. OBJECTIVE: The objective of the study was to determine VLDL-TG, glucose, and palmitate kinetics during fasting and hyperinsulinemia in men with (NAFLD+) and without NAFLD (NAFLD-). DESIGN: Twenty-seven nondiabetic, upper-body obese (waist to hip ratio > 0.9, body mass index > 28 kg/m2) men, 18 NAFLD+, and nine NAFLD- determined by magnetic resonance spectroscopy were enrolled.14C-labeled VLDL-TG and 3H-labeled glucose and palmitate tracers were applied in combination with indirect calorimetry and breath samples to assess kinetics and substrate oxidations postabsorptively and during a hyperinsulinemic-euglycemic clamp. Dual X-ray absorptiometry and magnetic resonance imaging assessed body composition. RESULTS: Liver fat content was greater in NAFLD+ than NAFLD- men (21.0% vs 3.7%), even though body composition, metabolites (except triglycerides), and insulin were similar in the groups. Insulin suppression of VLDL-TG secretion (P = .0001), oxidation (P = .0003), and concentration (P= .008) as well as percentage decreases were lower in NAFLD+ than NAFLD- men (secretion: 31.9% +/- 17.2% vs 64.7% +/- 19.9%; oxidation: -9.0% +/- 24.7% vs 46.5% +/- 36.6%; concentration: 11.9% +/- 20.7% vs 56.2% +/- 22.9%, all P < .001). Likewise, lower insulin suppression of very low-density lipoprotein particle size was present in NAFLD+ than NAFLD- men (P = .0002). Conversely, insulin suppression of endogenous glucose production was similar in the groups. CONCLUSIONS: Compared with endogenous glucose production, the inability of NAFLD+ men to suppress VLDL-TG kinetics to compensate for the increased liver fat content seems to be an early pathophysiological manifestation of male NAFLD+. These data suggest therapeutic targets reducing liver fat content may ameliorate metabolic abnormalities associated with NAFLD and presumably diabetes. PMID- 26829440 TI - Obesity-associated Inflammation Induces microRNA-155 Expression in Adipocytes and Adipose Tissue: Outcome on Adipocyte Function. AB - CONTEXT: Obesity alters adipose tissue's metabolic and endocrine functions and causes a chronic local and systemic low-grade inflammatory state to develop, generating obesity-associated complications. In the last decade, many entities contributing to and regulating this inflammatory state have been identified, among which are microRNAs. OBJECTIVE: This study aimed to identify microRNA regulated in inflamed adipocytes and adipose tissue, and its effect on adipocyte biology. DESIGN AND RESULTS: We screened the expression profile of TNFalpha treated adipocytes (a major pro-inflammatory protein expressed in obese adipose tissue), and identified miR-155 as the most responsive microRNA. The involvement of TNFalpha on the basal miR-155 expression was confirmed in the adipose tissue of Tnfa-/- mice where miR-155 was significantly reduced. Also, mice overexpressing p65 or invalidated for p65 in adipose tissue respectively increased and decreased miR-155 expression, in line with the involvement of the nuclear factor kappaB (NF-kappaB) pathway in miR-155 induction. miR-155 expression was higher in obese subjects' adipose tissue than in that of normal weight subjects, and correlated with TNFalpha expression and body mass index. Gain and loss of function of miR-155 showed its effect on adipocyte function, probably via its ability to target PPARgamma mRNA 3'UTR. Interestingly, miR-155 overexpression also resulted in an increased inflammatory state in adipocytes. CONCLUSION: Altogether, these data are evidence of a proinflammatory loop mediated by NF-kappaB and miR-155 that could participate in the amplification of inflammatory status in adipocytes. PMID- 26829442 TI - beta-cell Mass in Nondiabetic Autoantibody-Positive Subjects: An Analysis Based on the Network for Pancreatic Organ Donors Database. AB - CONTEXT: Little information is available about beta-cell mass in antibody positive (Ab+) nondiabetic subjects. OBJECTIVE: We have investigated whether the publicly available virtual slides of the Network for Pancreatic Organ Donors with Diabetes (nPOD) project can be used to assess beta-cell mass and distribution in nondiabetic antibody-negative (Ab-) and antibody-positive (Ab+) subjects and in patients with recent-onset type 1 diabetes (T1D). SUBJECTS AND METHODS: We developed a semi-automated quantification method and applied it to 415 insulin stained slides from 69 Ab- subjects, 101 slides from 18 Ab+ subjects, and 46 slides from eight recent-onset (<3 y) T1D subjects. Among these subjects, 48, 17, and seven had an available pancreatic mass, respectively, and were used for the quantification of beta-cell mass. RESULTS: In Ab- subjects, the beta-cell and endocrine mass were 0.66 +/- 0.42 and 1.0 +/- 0.65 g, respectively. Nonexocrine tissue represented 29% of pancreatic area, a proportion that increased with age. Proportional beta-cell area relative to total pancreatic area was higher in the tail compared with head (0.83 vs 0.71%; P < .001). In Ab+ subjects, beta-cell mass and beta-cell area were similar to those of Ab- individuals, whereas these parameters were dramatically decreased in recent-onset T1D patients. CONCLUSION: The virtual slides of the nPOD project can be used for quantification projects. In Ab+ nondiabetic subjects, the beta-cell mass was not decreased. However, as this cohort is largely composed of donors from the general population, with a single autoantibody, future studies with a larger number of donors with multiple autoantibodies and predisposing human leucocyte antigen genes are required to better define the dynamics of beta-cell destruction in the preclinical phases of T1D. PMID- 26829443 TI - Vitamin D 20,000 IU per Week for Five Years Does Not Prevent Progression From Prediabetes to Diabetes. AB - CONTEXT: Vitamin D deficiency is associated with insulin resistance and risk of future diabetes. OBJECTIVE: The objective of the study was to test whether supplementation with vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes mellitus (T2DM). DESIGN: This was a randomized controlled trial performed in 2008 through 2015. SETTING: The study was conducted at the clinical research unit at a teaching hospital. PATIENTS: Five hundred eleven subjects (mean age 62 y, 314 males) with prediabetes diagnosed with an oral glucose tolerance test as part of the Tromso Study 2007-2008 were included. A total of 256 were randomized to vitamin D and 255 to placebo. Twenty-nine subjects in the vitamin D and 24 in the placebo group withdrew because of adverse events. INTERVENTIONS: Interventions included vitamin D (cholecalciferol) 20 000 IU/wk vs placebo for 5 years. Annual oral glucose tolerance tests were performed. MAIN OUTCOME MEASURE: Progression to T2DM was the main outcome measure. Secondary outcomes were change in glucose levels, insulin resistance, serum lipids, and blood pressure. RESULTS: The mean baseline serum 25-hydroxyvitamin D level was 60 nmol/L (24 ng/mL). One hundred three in the vitamin D and 112 in the placebo group developed T2DM (hazard risk 0.90; 95% confidence interval 0.69-1.18, Cox regression, P = .45, intention to treat analysis). No consistent significant effects on the other outcomes were seen. Subgroup analyses in subjects with low baseline 25-hydroxyvitamin D yielded similar results. No serious side effects related to the intervention were recorded. CONCLUSIONS: In subjects without vitamin D deficiency, vitamin D supplementation is unlikely to prevent progression from prediabetes to diabetes. Very large studies with inclusion of vitamin D-deficient subjects will probably be needed to show such a putative effect. This study tested if supplementation with vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes (T2DM). PMID- 26829444 TI - Specific Metabolic Profiles and Their Relationship to Insulin Resistance in Recent-Onset Type 1 and Type 2 Diabetes. AB - CONTEXT: Insulin resistance reflects the inadequate insulin-mediated use of metabolites and predicts type 2 diabetes (T2D) but is also frequently seen in long-standing type 1 diabetes (T1D) and represents a major cardiovascular risk factor. OBJECTIVE: We hypothesized that plasma metabolome profiles allow the identification of unique and common early biomarkers of insulin resistance in both diabetes types. DESIGN, SETTING, AND PATIENTS: Two hundred ninety-five plasma metabolites were analyzed by mass spectrometry from patients of the prospective observational German Diabetes Study with T2D (n = 244) or T1D (n = 127) and known diabetes duration of less than 1 year and glucose-tolerant persons (CON; n = 129). Abundance of metabolites was tested for association with insulin sensitivity as assessed by hyperinsulinemic-euglycemic clamps and related metabolic phenotypes. MAIN OUTCOMES MEASURES: Sixty-two metabolites with phenotype-specific patterns were identified using age, sex, and body mass index as covariates. RESULTS: Compared with CON, the metabolome of T2D and T1D showed similar alterations in various phosphatidylcholine species and amino acids. Only T2D exhibited differences in free fatty acids compared with CON. Pairwise comparison of metabolites revealed alterations of 28 and 49 metabolites in T1D and T2D, respectively, when compared with CON. Eleven metabolites allowed differentiation between both diabetes types and alanine, alpha-amino-adipic acid, isoleucin, and stearic acid showed an inverse association with insulin sensitivity in both T2D and T1D combined. CONCLUSION: Metabolome analyses from recent-onset T2D and T1D patients enables identification of defined diabetes type specific differences and detection of biomarkers of insulin sensitivity. These analyses may help to identify novel clinical subphenotypes diabetes. PMID- 26829445 TI - The use of coenzyme Q10 and DHEA during IUI and IVF cycles in patients with decreased ovarian reserve. AB - OBJECTIVE: The objective of this study is to compare the combination of dehydroepiandrosterone (DHEA) and coenzyme Q10 (CoQ10) (D + C) with DHEA alone (D) in intrauterine insemination (IUI) and in vitro fertilization (IVF) cycles among patients with decreased ovarian reserve. METHODS: We retrospectively extracted data from patients charts treated by DHEA with/without CoQ10 during IUI or IVF between February 2006 and June 2014. Prestimulation parameters included age, BMI, day 3 FSH and antral follicular count (AFC). Ovarian response parameters included total gonadotropins dosage, peak serum estradiol, number of follicles > 16 mm and fertilization rate. Clinical outcomes included clinical and ongoing pregnancy rates. RESULTS: Three hundred and thirty IUI cycles involved D + C compared with 467 cycles of D; 78 IVF cycles involved D + C and 175 D. In both IUI and IVF, AFC was higher with D + C compared with D (7.4 +/- 5.7 versus 5.9 +/- 4.7, 8.2 +/- 6.3 versus 5.2 +/- 5, respectively, p < 0.05). D + C resulted in a more follicles > 16 mm during IUI cycles (3.3 +/- 2.3 versus 2.9 +/ 2.2, respectively, p = 0.01), while lower mean total gonadotropin dosage was administered after D + C supplementation compared with D (3414 +/- 1141 IUs versus 3877 +/- 1143 IUs respectively, p = 0.032) in IVF cycles. Pregnancy and delivery rates were similar for both IUI and IVF. CONCLUSION: D + C significantly increases AFC and improves ovarian responsiveness during IUI and IVF without a difference in clinical outcome. PMID- 26829446 TI - RUPTURED RETINAL ARTERIAL MACROANEURYSM ON THE OPTIC DISK. AB - PURPOSE: To describe multimodal imaging findings in a patient presenting with an occult optic disk macroaneurysm. METHODS: A 54-year-old woman presented with decreased vision in the right eye secondary to preretinal, intraretinal, and optic disk hemorrhage. RESULTS: Ancillary fluorescein angiography revealed evidence of an occult optic disk macroaneurysm that was not realized on fundoscopic examination. Subsequent optical coherence tomography obtained once the hemorrhage resolved demonstrated a thrombosed macroaneurysm with an adjacent ring of exudate. CONCLUSION: Detection of optic disk macroaneurysms at the time of initial presentation can be difficult because of concurrent overlying hemorrhage, but should nevertheless be kept in the differential when macular hemorrhage in multiple retinal layers is observed. PMID- 26829447 TI - SUCCESSFUL REPAIR OF RECURRENT OPTIC DISK PIT MACULOPATHY WITH AUTOLOGOUS PLATELET RICH PLASMA: REPORT OF A SURGICAL TECHNIQUE. AB - PURPOSE: To describe vitreoretinal surgical technique of using autologous platelet-rich plasma to aid in surgical repair of optic pit maculopathy refractive to previous vitrectomy. METHODS: A case of an 18-year-old woman presenting with serous macular detachment secondary to optic pit is reported. Patient had previously undergone vitrectomy and peripapillary laser, but had recurrence of subretinal fluid and worsening visual acuity. Autologous platelet rich plasma was harvested from the patient's blood and purified using Arthrex ACP kit (Arthrex, Inc, Naples, FL). Repeat pars plana vitrectomy was performed with internal limiting membrane peeling extending to the optic nerve. Platelet-rich plasma was layered over the pit and long-acting gas tamponade performed with face down positioning. RESULTS: At 8 months of follow-up, subretinal fluid was resolved, the connection between optic pit and subretinal space collapsed and the ellipsoid zone near completely reconstituted on optical coherence tomography. The patient's vision improved significantly from 20/100 to 20/50, which is largely limited by posterior subcapsular cataract. CONCLUSION: Platelet-rich plasma can augment anatomical and visual outcomes in surgical repair of optic pit maculopathy. PMID- 26829448 TI - COTTON-WOOL SPOTS AFTER USE OF MACITENTAN FOR PULMONARY ARTERIAL HYPERTENSION. AB - PURPOSE: To report a case of transient, bilateral cotton spots after initiation of macitentan, an endothelin receptor antagonist used for the treatment of pulmonary arterial hypertension. METHODS: Case report. RESULTS: A 76-year-old woman with WHO Class IIIb pulmonary arterial hypertension was referred for evaluation of bilateral cotton-wool spots 1 week after starting macitentan therapy. The patient was asymptomatic and visual acuity was 20/25 in each eye. Fluorescein angiography and optical coherence tomography were completed. Given lack of symptoms and alternative treatment options, the patient was observed closely. The cotton-wool spots resolved 8 weeks after presentation and visual acuity remained stable at 20/25. Throughout the observation period, average mean arterial pressure was within normal limits at 84.8. CONCLUSION: In patients using endothelin receptor antagonists, medication side effect should be considered in the differential diagnosis of cotton-wool spots. PMID- 26829449 TI - Varicella immunization requirements for US colleges: 2014-2015 academic year. AB - OBJECTIVE: To obtain information on varicella prematriculation requirements in US colleges for undergraduate students during the 2014-2015 academic year. PARTICIPANTS: Health care professionals and member schools of the American College Health Association (ACHA). METHODS: An electronic survey was sent to ACHA members regarding school characteristics and whether schools had policies in place requiring that students show proof of 2 doses of varicella vaccination for school attendance. RESULTS: Only 27% (101/370) of schools had a varicella prematriculation requirement for undergraduate students. Only 68% of schools always enforced this requirement. Private schools, 4-year schools, northeastern schools, those with <5,000 students, and schools located in a state with a 2-dose varicella vaccine mandate were significantly more likely to have a varicella prematriculation requirement. CONCLUSIONS: A small proportion of US colleges have a varicella prematriculation requirement for varicella immunity. College vaccination requirements are an important tool for controlling varicella in these settings. PMID- 26829450 TI - Energy balance of biofuel production from biological conversion of crude glycerol. AB - Crude glycerol, a by-product of biodiesel production, has gained significant attention as a carbon source for biofuel production. This study evaluated the energy balance of biodiesel, hydrogen, biogas, and ethanol production from 3.48 million L of crude glycerol (80% w/v). The conversion efficiency (energy output divided by energy invested) was 1.16, 0.22, 0.27, and 0.40 for the production of biodiesel, hydrogen, biogas, and ethanol respectively. It was found that the use of crude glycerol for biodiesel production was an energy gain process, with a positive energy balance and conversion efficiency of greater than 1. The energy balance revealed a net energy gain of 5226 GJ per 1 million kg biodiesel produced. Production of hydrogen, biogas and ethanol from crude glycerol were energy loss processes. Therefore, the conversion of crude glycerol to lipids and subsequently to biodiesel is suggested to be a better option compared to hydrogen, biogas, or ethanol production with respect to energy balance. PMID- 26829451 TI - Conflict resolution in the zoning of eco-protected areas in fast-growing regions based on game theory. AB - Zoning eco-protected areas is important for ecological conservation and environmental management. Rapid and continuous urban expansion, however, may exert negative effects on the performance of practical zoning designs. Various methods have been developed for protected area zoning, but most of them failed to consider the conflicts between urban development (for the benefit of land developers) and ecological protection (local government). Some real-world zoning schemes even have to be modified occasionally after the lengthy negotiations between the government and land developers. Therefore, our study has presented a game theory-based method to deal with this problem. Future urban expansion in the study area will be predicted by a logistic regression cellular automaton, while eco-protected areas will be delimitated using multi-objective optimization algorithm. Then, two types of conflicts between them can be resolved based on game theory, a theory of decision-making. We established a two-person dynamic game for each conflict zone. The ecological compensation mechanism was taken into account by simulating the negotiation processes between the government and land developers. A final zoning scheme can be obtained when the two sides reach agreements. The proposed method is applied to the eco-protected area zoning in Guangzhou, a fast-growing city in China. The experiments indicate that the conflicts between eco-protection and urban development will inevitably arise when using only traditional zoning methods. Based on game theory, our method can effectively resolve those conflicts, and can provide a relatively reasonable zoning scheme. This method is expected to support policy-making in environmental management and urban planning. PMID- 26829452 TI - An overview of principles of odor production, emission, and control methods in wastewater collection and treatment systems. AB - Odorous gases are the most important reason that people register complaints with organizations responsible for wastewater collection and treatment systems (WCTS). Although several studies have been conducted for prevention and control of odorous gases, no comprehensive research exists about recent achievements in this area. The aim of the present study is to collect and categorize the new achievements in preventing and controlling odorous gases in WCTS. Two strategies for controlling odor emissions from WCTS are (1) prevention of odor production and (2) removal of odorous compounds from emissions of WCTS. Between the two, priority goes to preventing odorous compounds' production. Several methods have been developed to prevent odor production, such as increasing oxidation reduction potential; inhibiting the activity of sulfide reducing bacteria; chemical removal of hydrogen sulfide; applying formaldehyde and paraformaldehyde to prevent hydrogen sulfide production; and using fuel cells in hydrogen sulfide inhibition and gradual release of oxygen in gas phase by using MgO2 or CaO2. In addition to preventing odorous compounds in WCTS, many other methods have been introduced to remove odorous compounds from emissions of WCTS, such as biofilters; bioscrubbers; biotrickling filters; suspended growth reactors; and membrane bioreactors and scrubbers. Through this review, responsible organizations can find new, effective, and economical strategies to prevent and control odorous gases in WCTS. PMID- 26829453 TI - Risk of Injury According to Attention Deficit Hyperactivity Disorder, Comorbid Mental Illness, and Medication Therapy. AB - INTRODUCTION: We identify the risk of selected types of injuries among patients with ADHD or ADHD and comorbid mental illness. We also assess whether selected medications used by patients with ADHD increase the risk of comorbid mental illness or influence the association between ADHD and injury. METHODS: A retrospective cohort study design was conducted using medical claims data from the Deseret Mutual Benefit Administrators (DMBA). ADHD diagnosis, injury, medication, and demographic data were extracted from claims files during 2001 2013. Rate ratios were adjusted for age, sex, and calendar year. RESULTS: Patients with ADHD were 7.9 (95% CI 7.6-8.2) times more likely to have psychosis, 5.5 (3.9-7.8) times more likely to have alcohol- or drug-induced psychosis, and 6.0 (5.9-6.2) times more likely to have neurotic or personality disorder. Therapy with amphetamine was positively associated with neurotic or personality disorder (rate ratio=1.08, 1.02-1.15); methylphenidate was negatively associated with neurotic or personality disorder (0.90, 0.84-0.97); and atomoxetine was positively associated with psychosis (1.33, 1.21-1.46), alcohol- or drug-induced psychosis (2.38, 1.04-5.43), and neurotic or personality disorder (2.38, 1.04 5.43). ADHD was associated with an increased risk of injury, with ADHD and comorbid mental illness having a stronger increased risk of injury. Psychostimulants ameliorated the increased risk of injury for patients with ADHD. CONCLUSION: Patients with ADHD have an increased risk of injury, significantly more so for those with ADHD and comorbid mental illness. Psychostimulants can lower the risk of injury among patients with ADHD. PMID- 26829454 TI - The elite scholar in Coronary Artery Disease. PMID- 26829455 TI - Drug-eluting balloon: early enthusiasm being tempered by growing uncertainty. PMID- 26829456 TI - Novel sirolimus-eluting stents: back to the future with third-generation drug eluting stents? PMID- 26829457 TI - Measuring and Suppressing the Oxidative Damage to DNA During Cu(I)-Catalyzed Azide-Alkyne Cycloaddition. AB - We have used the quantitative polymerase chain reaction (qPCR) to measure the extent of oxidative DNA damage under varying reaction conditions used for copper(I)-catalyzed click chemistry. We systematically studied how the damage depends on a number of key reaction parameters, including the amounts of copper, ascorbate, and ligand used, and found that the damage is significant under nearly all conditions tested, including those commonly used for bioconjugation. Furthermore, we discovered that the addition of dimethyl sulfoxide, a known radical scavenger, into the aqueous mixture dramatically suppresses DNA damage during the reaction. We also measured the efficiency of cross-linking two short synthetic oligonucleotides via click chemistry, and found that the reaction could proceed reasonably efficiently even with DMSO present. This approach for screening both DNA damage and reactivity under a range of reaction conditions will be valuable for improving the biocompatibility of click chemistry, and should help to extend this powerful synthetic tool for both in vitro and in vivo applications. PMID- 26829458 TI - Adoptive cell therapy: a highly successful individualized therapy for melanoma with great potential for other malignancies. AB - Adoptive cell therapy (ACT) by infusion of autologous or redirected tumor specific T-cells has had a major impact on the treatment of several metastasized malignancies that were until now hardly treatable. Recent findings provide a more profound knowledge on the underlying mechanisms of success and allow the optimization of the ACT protocol with respect to (1) the treatment related side effects, (2) the quality and specificity of infused T-cells, and (3) the immunosuppressive phenotype of the tumor environment. In this review, the results and insights in the success of ACT as well as the possibilities to improve ACT and its exploitation as treatment option for various metastatic cancer types, will be discussed. PMID- 26829460 TI - A case of hypopharyngeal cancer with stenosis, perforation, and pyogenic spondylitis development after chemoradiotherapy. AB - INTRODUCTION: Chemoradiotherapy plays an important role in preserving function and morphology in head and neck cancer. However, in a few cases, chemoradiotherapy has been shown to result in late complications, such as hypopharyngeal perforation, which is very rare. PRESENTATION OF CASE: A 65-year old man, who had undergone chemoradiotherapy for hypopharyngeal cancer 30 months previously, presented with high fever and neck pain. He subsequently developed hypopharyngeal stenosis, hypopharyngeal perforation, and a retropharyngeal abscess followed by pyogenic spondylitis. He underwent surgical treatment (resection with reconstruction) and was administered an antibacterial agent and steroids for an extended period. This treatment regimen was successful, and the patient has survived disease-free without symptoms. DISCUSSION: Chemoradiotherapy induced hypopharyngeal perforation is an extremely rare condition. In the present case, the perforation was large (2cm), and the hypopharyngeal cavity was originally constricted. Pharyngeal reconstruction with a jejunal autograft was therefore necessary. Through the present case, we reconfirmed that although the primary purpose of chemoradiotherapy is organ preservation, it can also lead to organ destruction and fatal complications. It is important that physicians be aware of the possibility of hypopharyngeal perforation so as to avoid delayed diagnosis and treatment of similar rare cases. CONCLUSION: Hypopharyngeal perforation can sometimes be fatal because it can lead to pyogenic spondylitis. Suitable surgical techniques and appropriate doses of antibacterial agents for long-term use were appropriate treatments for the patient in this case. PMID- 26829459 TI - Nesfatin-1 improves oxidative skin injury in normoglycemic or hyperglycemic rats. AB - Hyperglycemia is one of the major causes of suppressed angiogenesis and impaired wound healing leading to chronic wounds. Nesfatin-1 a novel peptide was reported to have antioxidant and anti-apoptotic properties. This study is aimed to investigate the potential healing-promoting effects of nesfatin-1 in non-diabetic or diabetic rats with surgical wounds. In male Sprague-Dawley rats, hyperglycemia was induced by intraperitoneal (ip) injection of streptozotocin (55 mg/kg). Under anesthesia, dorsum skin tissues of normoglycemic (n=16) and hyperglycemic rats were excised (2 * 2 cm, full-thickness), while control rats (n=16) had neither hyperglycemia nor wounds. Half of the rats in each group were treated ip with saline, while the others were treated with nesfatin-1 (2 MUg/kg/day) for 3 days until they were decapitated. Plasma interleukin-1-beta (IL-1beta), transforming growth factor-beta (TGF-beta-1), IL-6 levels, and dermal tissue malondialdehyde (MDA), glutathione (GSH) levels, myeloperoxidase (MPO) and caspase-3 activity were measured. For histological examination, paraffin sections were stained with hematoxylin-eosin or Masson's trichrome and immunohistochemistry for vascular endothelial growth factor (VEGF) was applied. ANOVA and Student's t-tests were used for statistical analysis. Compared to control rats, skin MPO activity, MDA and caspase-3 levels were increased similarly in saline-treated normo- and hyperglycemic rats. Nesfatin-1 depressed MDA, caspase-3, MPO activity and IL 1beta with concomitant elevations in dermal GSH and plasma TGF-beta-1 levels. Histopathological examination revealed regeneration of epidermis, regular arrangement of collagen fibers in the dermis and a decrease in VEGF immunoreactivity in the epidermal keratinocytes of nesfatin-1-treated groups. Nesfatin-1 improved surgical wound healing in both normo- and hyperglycemic rats via the suppression of neutrophil recruitment, apoptosis and VEGF activation. PMID- 26829461 TI - pH-Mediated Fluorescent Polymer Particles and Gel from Hyperbranched Polyethylenimine and the Mechanism of Intrinsic Fluorescence. AB - We report that fluorescence properties and morphology of hyperbranched polyethylenimine (hPEI) cross-linked with formaldehyde are highly dependent on the pH values of the cross-linking reaction. Under acidic and neutral conditions, water-soluble fluorescent copolymer particles (CPs) were produced. However, under basic conditions, white gels with weak fluorescence emission would be obtained. The water-soluble hPEI-formaldehyde (hPEI-F) CPs show strong intrinsic fluorescence without the conjugation to any classical fluorescent agents. By the combination of spectroscopy and microscopy techniques, the mechanism of fluorescence emission was discussed. We propose that the intrinsic fluorescence originates from the formation of a Schiff base in the cross-linking process between hPEI and formaldehyde. Schiff base bonds are the fluorescence-emitting moieties, and the compact structure of hPEI-F CPs plays an important role in their strong fluorescence emission. The exploration on fluorescence mechanism may provide a new strategy to prepare fluorescent polymer particles. In addition, the investigation shows that the hPEI-F CPs hold potential as a fluorescent probe for the detection of copper ions in aqueous media. PMID- 26829462 TI - A new perspective on the treatment of complicated giant emphysematous bulla A case report. AB - We report a case of 31 years-old female suffering from complicated giant bulla in the right upper pulmonary lobe. The patient was admitted to our hospital with a radiologic diagnosis of hydro - pneumothorax treated by chest tube in a first time, and later, for prolonged air leaks, by uniportal VATS with a single 4-cm skin incision. We have observed a giant ruptured bulla in right upper lobe, so we have performed bullectomy and mechanical pleurodesis. This case, in our knowledge, represents the first giant bulla resection performed by uniportal VATS. KEY WORDS: Giant bulla, Giant bullous emphysema, Uniportal VATS. PMID- 26829463 TI - The Effects of Using the International Versus Comprehensive System Rorschach Norms For Children, Adolescents, and Adults. AB - Currently, there is some debate about whether to use Comprehensive System norms (CS; Exner, 2003 ) or the Composite International Reference Values (CIRV; Meyer, Erdberg, & Shaffer, 2007 ) when interpreting Rorschach Inkblot Method (RIM; Rorschach, 1921 ) protocols administered with the CS method. The goal of this study is to assist clinicians in making this decision by providing information about the effects of choosing one option or the other. Accordingly, this research evaluates the effects of using the CS versus CIRV norms with children, adolescents, and adults. First, we identified 43 variables for which the CS and the CIRV for children and adolescents differ from each other by at least a Cohen's d value of .50. Next, we evaluated whether these divergent variables are the same as those previously identified as divergent for the adult population. Results showed that for both children and adolescents, as well as for adults, relying on CS norms versus CIRV would result in interpretations that are more pathological in terms of (a) perception and thinking, (b) psychological resources and cognitive and emotional abilities, and (c) representations of human relationships. A discussion on the clinical effects of using one versus the other set of norms follows. PMID- 26829464 TI - Design of In Situ Poled Ce(3+)-Doped Electrospun PVDF/Graphene Composite Nanofibers for Fabrication of Nanopressure Sensor and Ultrasensitive Acoustic Nanogenerator. AB - We report an efficient, low-cost in situ poled fabrication strategy to construct a large area, highly sensitive, flexible pressure sensor by electrospun Ce(3+) doped PVDF/graphene composite nanofibers. The entire device fabrication process is scalable and enabling to large-area integration. It can able to detect imparting pressure as low as 2 Pa with high level of sensitivity. Furthermore, Ce(3+)-doped PVDF/graphene nanofiber based ultrasensitive pressure sensors can also be used as an effective nanogenerator as it generating an output voltage of 11 V with a current density ~6 nA/cm(2) upon repetitive application of mechanical stress that could lit up 10 blue light emitting diodes (LEDs) instantaneously. Furthermore, to use it in environmental random vibrations (such as wind flow, water fall, transportation of vehicles, etc.), nanogenerator is integrated with musical vibration that exhibits to power up three blue LEDs instantly that promises as an ultrasensitive acoustic nanogenerator (ANG). The superior sensing properties in conjunction with mechanical flexibility, integrability, and robustness of nanofibers enabled real-time monitoring of sound waves as well as detection of different type of musical vibrations. Thus, ANG promises to use as an ultrasensitive pressure sensor, mechanical energy harvester, and effective power source for portable electronic and wearable devices. PMID- 26829465 TI - Treatment of vertical heterophoria ameliorates persistent post-concussive symptoms: A retrospective analysis utilizing a multi-faceted assessment battery. AB - PRIMARY OBJECTIVE: To examine the effectiveness of neutralizing prismatic lenses for reduction of headache, dizziness and anxiety in patients with persistent post concussive symptoms and vertical heterophoria (VH). BACKGROUND: Approximately 5 10% of patients with traumatic brain injury (TBI) develop persistent post concussive symptoms. Many rehabilitation/treatment modalities are tried, but are largely unsuccessful, indicating a need for more effective treatment. DESIGN AND METHOD: This retrospective study included 38 patients with persistent post concussive symptoms, who were diagnosed by an optometric binocular vision sub specialist with VH (a sub-set of binocular vision dysfunction [BVD] that manifests as vertical eye and image misalignment). Data was collected both before and after prism application and included validated survey instruments for headache, dizziness, anxiety and BVD symptom burden; subjective rating (0-10 scale) of headache, dizziness and anxiety severity; and a sub-analysis of the BVD survey instrument questions that pertain specifically to headache, dizziness and anxiety. Upon conclusion of treatment, subjective assessment of overall improvement of heterophoria symptoms was obtained utilizing a 10 cm visual analogue scale. OUTCOMES: Results demonstrated marked reduction in all measures of headache, dizziness and anxiety (19.1-60.8%) and an overall subjective improvement of VH symptoms of 80.2%. CONCLUSIONS: Neutralizing prismatic lenses are an effective treatment of headache, dizziness and anxiety in patients with persistent post-concussive symptoms and VH. PMID- 26829467 TI - Optimization of a recombinant human growth hormone purification process using quality by design. AB - This work describes a strategy to optimize a downstream processing of a recombinant human growth hormone (rhGH) by incorporating a quality by design approach toward meeting higher quality specifications. The optimized process minimized the presence of impurities and degradation by-products during manufacturing by the establishment of in-process controls. Capillary zone electrophoresis, reverse phase, and size-exclusion chromatographies were used as analytical techniques to establish new critical process parameters for the solubilization, capture, and intermediate purification steps aiming to maintain rhGH quality by complying with pharmacopeial specifications. The results indicated that the implemented improvements in the process allowed the optimization of the specific recovery and purification of rhGH without compromising its quality. In addition, this optimization facilitated the stringent removal of the remaining impurities in further polishing stages, as demonstrated by the analysis of the obtained active pharmaceutical ingredient. PMID- 26829466 TI - Structural characterization of twisted gastrulation provides insights into opposing functions on the BMP signalling pathway. AB - Twisted gastrulation (Tsg) and chordin are secreted glycoproteins that function together as BMP (bone morphogenetic protein) antagonists to regulate BMP growth factor signalling. Chordin binds to BMPs, preventing them from interacting with their receptors and Tsg is known to strengthen this inhibitory complex. Tsg also acts as a BMP agonist by promoting cleavage of chordin by tolloid-family proteinases. Here we explore the structural mechanism through which Tsg exerts this dual activity. We have characterized the nanoscale structure of human Tsg using in-solution biomolecular analysis and show that Tsg is a globular monomer with a flattened cross shape. Tsg has a high proportion of N-linked glycans, in relation to its molecular weight, which supports a role in solubilising BMPs. Tsg binds with high affinity to the C-terminal region of chordin and was also able to inhibit BMP-7 signalling directly but did not have an effect on BMP-4 signalling. Although both Tsg and mammalian tolloid are involved in chordin cleavage, no interaction could be detected between them using surface plasmon resonance. Together these data suggest that Tsg functions as a BMP-agonist by inducing conformational change in chordin making it more susceptible to tolloid cleavage and as a BMP-antagonist either independently or via a chordin-mediated mechanism. Following single cleavage of chordin by tolloids, Tsg continues to strengthen the inhibitory complex, supporting a role for partially cleaved chordin in BMP regulation. PMID- 26829468 TI - Outcomes of Primary Transconjunctival 23-Gauge Vitrectomy in the Diagnosis and Treatment of Presumed Endogenous Fungal Endophthalmitis. AB - PURPOSE: To report the outcomes of primary transconjunctival 23-gauge (23-G) vitrectomy in the diagnosis and treatment of presumed endogenous fungal endophthalmitis (EFE). METHODS: Retrospective analysis of patients with EFE who underwent diagnostic transconjunctival 23-G vitrectomy at a tertiary referral center. RESULTS: Nineteen eyes of 15 patients with EFE were included in the study. Four patients had bilateral and 11 patients unilateral disease. Sixteen eyes of 15 patients underwent 23-G vitrectomy to confirm the diagnosis using vitreous culture, polymerase chain reaction, and histopathologic examinations. All affected eyes were treated with intravitreal amphotericin B 5 ug/0.1 mL. Fourteen patients received additional systemic antifungal therapy. Diagnostic 23 G vitrectomy confirmed the diagnosis of EFE in 75% of the eyes (12/16). Candida was found to be a causative agent in 62.5% and Aspergillus in 12.5% of the eyes. Retinal detachment was the most common complication (42% of eyes). CONCLUSIONS: EFE can be easily confirmed using primary 23-G vitrectomy. PMID- 26829469 TI - Opportunities and challenges in developing relevant animal models for Alzheimer's disease. AB - A major impediment to the development of safe and effective therapeutics in Alzheimer's disease (AD) lies in difficulties in translating research findings across species: therapies that work in rodents often do not translate to humans. A route to bridge the gap between promising rodent research and the human clinical condition consists in using non-human primates (NHPs), which are phylogenetically much closer to humans. In this article, we discuss the importance of investigating disease mechanisms from cell culture, through different animal models of disease. We highlight that developing a viable, validated NHP AD model will likely be a key step toward understanding AD-relevant pathogenic mechanisms and for developing therapies that will effectively translate to the human disease condition. PMID- 26829470 TI - Activation of mGluR1 contributes to neuronal hyperexcitability in the rat anterior cingulate cortex via inhibition of HCN channels. AB - Neuronal hyperexcitability in the anterior cingulate cortex (ACC) is considered as one of the most important pathological changes responsible for the chronification of neuropathic pain. However, the underlying mechanisms remain elusive. In the present study, we investigated the possible mechanisms using a rat model of chronic constriction injury (CCI) to the sciatic nerve. We found a substantial decrease in hyperpolarization-activated/cyclic nucleotide-gated (HCN) currents in layer 5 pyramidal neurons (L5 PNs) in ACC slices, which dramatically increased the excitability of these neurons. This effect could be mimicked in sham slices by activating group 1 metabotropic glutamate receptors, and be blocked in CCI slices by inhibiting metabotropic glutamate receptor subtype 1 (mGluR1). Next, the inhibition of HCN currents was reversed by a protein kinase C (PKC) inhibitor, followed by a reduced neuronal hyperexcitability. Furthermore, HCN channel subtype 1 (HCN1) level was significantly reduced after CCI, whereas mGluR1 level increased. These changes were mainly observed in L5 of the ACC, where HCN1 and mGluR1 were highly colocalized. For behavioral tests, intra-ACC microinjection of mGluR1-shRNA suppressed the CCI-induced behavioral hypersensitivity, particularly thermal hyperalgesia, but not aversive behavior, and this effect was attenuated by the pre-blockade of HCN channels. Taken together, the neuronal hyperexcitability of ACC L5 PNs likely results from an upregulation of mGluR1 and a downstream pathway involving PKC activation and a downregulation of HCN1 in the early phase of neuropathic pain. These alterations may at least in part contribute to the development of behavioral hypersensitivity in CCI rats. PMID- 26829471 TI - Current Advances in the Use of Therapeutic Hypothermia. PMID- 26829472 TI - Discovery of tumor-specific irreversible inhibitors of stearoyl CoA desaturase. AB - A hallmark of targeted cancer therapies is selective toxicity among cancer cell lines. We evaluated results from a viability screen of over 200,000 small molecules to identify two chemical series, oxalamides and benzothiazoles, that were selectively toxic at low nanomolar concentrations to the same 4 of 12 human lung cancer cell lines. Sensitive cell lines expressed cytochrome P450 (CYP) 4F11, which metabolized the compounds into irreversible inhibitors of stearoyl CoA desaturase (SCD). SCD is recognized as a promising biological target in cancer and metabolic disease. However, SCD is essential to sebocytes, and accordingly SCD inhibitors cause skin toxicity. Mouse sebocytes did not activate the benzothiazoles or oxalamides into SCD inhibitors, providing a therapeutic window for inhibiting SCD in vivo. We thus offer a strategy to target SCD in cancer by taking advantage of high CYP expression in a subset of tumors. PMID- 26829473 TI - Assembly and clustering of natural antibiotics guides target identification. AB - Antibiotics are essential for numerous medical procedures, including the treatment of bacterial infections, but their widespread use has led to the accumulation of resistance, prompting calls for the discovery of antibacterial agents with new targets. A majority of clinically approved antibacterial scaffolds are derived from microbial natural products, but these valuable molecules are not well annotated or organized, limiting the efficacy of modern informatic analyses. Here, we provide a comprehensive resource defining the targets, chemical origins and families of the natural antibacterial collective through a retrobiosynthetic algorithm. From this we also detail the directed mining of biosynthetic scaffolds and resistance determinants to reveal structures with a high likelihood of having previously unknown modes of action. Implementing this pipeline led to investigations of the telomycin family of natural products from Streptomyces canus, revealing that these bactericidal molecules possess a new antibacterial mode of action dependent on the bacterial phospholipid cardiolipin. PMID- 26829475 TI - Changing ligand number and type within nanocylindrical domains through kinetically constrained self-assembly - impacts of ligand 'redundancy' on human mesenchymal stem cell adhesion and morphology. AB - In this paper, we firstly describe a facile method by which sequential attachment of different adhesion peptides to a nanotopographical, self-assembled block copolymer cell culture surface is made possible through orthogonal click chemistry. Functionalization of polystyrene-b-polyethylene oxide block copolymers (PS-PEO) with azide (PS-PEO-N3) and aminooxy (PS-PEO-ONH2) moieties permitted the use of orthogonal click chemistry protocols to sequentially add desired bioactive moieties. Thereafter, we show that co-self-assembly of non-functionalised PS-PEO with different amounts of these functionalized PS-PEOs produces polymer films having well-defined, hexagonally arrayed PEO nanocylinder domains, of near constant diameter (~17 nm diameter) and lateral spacing (~35 nm). The invariant diameters and lateral spacing of the nanodomains with changes in the amounts of PS-PEO-N3 and PS-PEO-ONH2 confirmed our ability to tune the number density of these functional groups locally within each PEO nanodomain. Stepwise conjugation of alkyne-terminated IKVAV or aldehyde-terminated RGD to the azide and aminooxy decorated nanodomains produced a series of substrates with increasing local number density of grafted adhesion peptides in each nanodomain. We then systematically investigated the impacts of ligand affinity and availability (leading to differing levels of redundancy) on cell integrin binding and adhesion behaviours. We show that with increasing numbers of single peptides (IKVAV or RGD) or with changes in the ratio of IKVAV and RGD peptides within each of the ~17 nm nanodomains of these films, there was significant changes in the number of hMSCs adhered and substantial modulation of cell morphology, cytoskeletal actin stress fibres and focal adhesion maturation. We observed that increases in the ratio of RGD to IKVAV peptides within the constrained surface nanodomains greatly enhanced hMSC adhesion, and effectively modulated hMSC morphology, cytoskeletal actin structures and focal adhesion number and maturity between the two extremes noted for the single peptides. The results presented suggest that these self assembled block copolymer substrates regulate hMSC adhesion and morphology through modulation of ligand affinity and ligand redundancy, and hence the effectiveness of integrin binding and mechanotransduction signalling. These novel 2D polymer substrates offer encoded and defined cues for cell adhesion at length scales previously unrealised and the results of this investigation expose a new parameter set by which the surfaces of biomaterials may be tailored for stem cell culture, selection and fate. PMID- 26829476 TI - Effects of grape seed extract as a natural antioxidant on growth performance, carcass characteristics and antioxidant status of rabbits during heat stress. AB - The present study aimed to investigate the effects of different levels of dietary supplementation of grape seed extract (GSE) on growth performance, carcass traits and antioxidant status of rabbits under heat stress conditions (temperature humidity index 87.5-93.5). Weaned male New Zealand White (NZW) rabbits about 6 weeks old (n = 144, mean body weight 705 g) were randomly allotted to four dietary groups. The Control group was fed a basal diet without GSE; the experimental groups received the basal diet with 100, 200 and 300 mg GSE/kg (Groups 100 GSE, 200 GSE and 300 GSE, respectively). The experimental period lasted for 8 weeks. Compared with other groups, rabbits of Group 300 GSE had the best body weight gain and feed conversion ratio and the lowest mortality. Dietary GSE improved carcass weight, percentage of hot carcass, intestine and edible giblets, while total non-edible parts were reduced (p <= 0.05) in comparison with the Control group. In Groups 200 GSE and 300 GSE, plasma total protein, albumin and globulin were increased (p <= 0.05). In contrast, all supplementation levels of GSE reduced (p <= 0.05) the plasma concentrations of total lipids, total cholesterol, triglycerides and low-density lipoproteins. Antioxidant enzymes of rabbits (superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase) and total antioxidant capacity in blood were increased (p <= 0.05) by adding dietary GSE. However, malondialdehyde was reduced (p <= 0.001) with increasing GSE levels. Generally, grape seeds can be considered as rich source of phenolic and flavonoid compounds. The results of the study revealed that all tested levels of GSE were useful as a natural protection against heat stress to maintain performance, carcass traits and antioxidant status and could reduce the negative effects of heat stress in rabbits. PMID- 26829474 TI - Acetylation of Aurora B by TIP60 ensures accurate chromosomal segregation. AB - Faithful segregation of chromosomes in mammalian cells requires bi-orientation of sister chromatids, which relies on the sensing of correct attachments between spindle microtubules and kinetochores. Although the mechanisms underlying cyclin dependent kinase 1 (CDK1) activation, which triggers mitotic entry, have been extensively studied, the regulatory mechanisms that couple CDK1-cyclin B activity to chromosome stability are not well understood. Here, we identified a signaling axis in which Aurora B activity is modulated by CDK1-cyclin B via the acetyltransferase TIP60 in human cell division. CDK1-cyclin B phosphorylates Ser90 of TIP60, which elicits TIP60-dependent acetylation of Aurora B and promotes accurate chromosome segregation in mitosis. Mechanistically, TIP60 acetylation of Aurora B at Lys215 protects Aurora B's activation loop from dephosphorylation by the phosphatase PP2A to ensure a robust, error-free metaphase-anaphase transition. These findings delineate a conserved signaling cascade that integrates protein phosphorylation and acetylation with cell cycle progression for maintenance of genomic stability. PMID- 26829477 TI - Mental health first aid for the elderly: A pilot study of a training program adapted for helping elderly people. AB - OBJECTIVES: Epidemiological studies have shown a high prevalence of mental illness among the elderly. Clinical data however indicate both insufficient detection and treatment of illnesses. Suggested barriers to treatment include conceptions that mental health symptoms belong to normal aging and lack of competence among staff in elderly care in detecting mental illness. A Mental Health First Aid (MHFA) training program for the elderly was developed and provided to staff in elderly care. The aim of this study was to investigate changes in knowledge in mental illness, confidence in helping a person, readiness to give help and attitudes towards persons with mental illness. METHOD: Single group pre-test-post-test design. RESULTS: The study group included staff in elderly care from different places in Sweden (n = 139). Significant improvements in knowledge, confidence in helping an elderly person with mental illness and attitudes towards persons with mental illness are shown. Skills acquired during the course have been practiced during the follow-up. CONCLUSIONS: The adaption of MHFA training for staff working in elderly care gives promising results. Improvements in self-reported confidence in giving help, attitudes towards persons with mental illness and actual help given to persons with mental illness are shown. However, the study design allows no firm conclusions and a randomized controlled trail is needed to investigate the effectiveness of the program. Outcomes should include if the detection and treatment of mental illness among the elderly actually improved. PMID- 26829480 TI - Chikungunya Virus Infection Alters Expression of MicroRNAs Involved in Cellular Proliferation, Immune Response and Apoptosis. AB - OBJECTIVE(S): Chikungunya virus (CHIKV) is a reemerging virus of significant importance that has caused large-scale outbreaks in the countries with a temperate climate. CHIKV causes debilitating arthralgia which can persist for weeks and up to a year. Fibroblast cells are the main target of CHIKV infection. In this study, we analyzed microRNA (miRNA) modulation in the fibroblast cells infected with CHIKV at an early stage of infection. METHODS: 760 miRNAs were analyzed for modulation following infection with CHIKV at 6 h after infection. Bioinformatic analysis was done to identify the signaling pathway that may be targeted by the significantly modulated miRNAs. Validation of the miRNAs was done using a singleplex miRNA assay and protein target validation of modulated miRNAs was done by Western blot analysis. RESULTS: Computational analysis of the significantly modulated miRNAs indicated their involvement in signaling pathways such as Toll-like receptor, mTOR, JAK-STAT and Pi3-Akt pathways, which have been shown to play important roles during CHIKV infection. Topoisomerase IIbeta, a target of two of the modulated miRNAs, was downregulated upon CHIKV infection. CONCLUSION(S): We identified several miRNAs that may play important roles in early events after CHIKV infection and can be potential therapeutic targets against CHIKV infection. PMID- 26829479 TI - Oral Administration of Polymyxin B Modulates the Activity of Lipooligosaccharide E. coli B against Lung Metastases in Murine Tumor Models. AB - INTRODUCTION: Polymyxin B (PmB) belongs to the group of cyclic peptide antibiotics, which neutralize the activity of LPS by binding to lipid A. The aim of this study was to analyze the effect of PmB on the biological activity of lipooligosaccharide (LOS E. coli B,rough form of LPS) in vitro and in experimental metastasis models. RESULTS: Cultures of murine macrophage J774A.1 cells and murine bone marrow-derived dendritic cells (BM-DC) stimulated in vitro with LOS and supplemented with PmB demonstrated a decrease in inflammatory cytokine production (IL-6, IL-10, TNF-alpha) and down-regulation of CD40, CD80, CD86 and MHC class II molecule expression. Additionally, PmB suspended in drinking water was given to the C57BL/6 mice seven or five days prior to the intravenous injection of B16 or LLC cells and intraperitoneal application of LOS. This strategy of PmB administration was continued throughout the duration of the experiments (29 or 21 days). In B16 model, statistically significant decrease in the number of metastases in mice treated with PmB and LOS (p<0.01) was found on the 14th day of the experiments, whereas the most intensive changes in surface antigen expression and ex vivo production of IL-6, IL-1beta and TNF-alpha by peritoneal cells were observed 7 days earlier. By contrast, antigen expression and ex vivo production of IL-6, IL-10, IFN-gamma by splenocytes remained relatively high and stable. Statistically significant decrease in LLC metastases number was observed after the application of LOS (p<0.01) and in the group of mice preconditioned by PmB and subsequently treated with LOS (LOS + PmB, p<0.01). CONCLUSIONS: In conclusion, prolonged in vivo application of PmB was not able to neutralize the LOS-induced immune cell activity but its presence in the organism of treated mice was important in modulation of the LOS-mediated response against the development of metastases. PMID- 26829478 TI - Assessment of a Standardized Pre-Operative Telephone Checklist Designed to Avoid Late Cancellation of Ambulatory Surgery: The AMBUPROG Multicenter Randomized Controlled Trial. AB - OBJECTIVES: To assess the impact of a standardized pre-operative telephone checklist on the rate of late cancellations of ambulatory surgery (AMBUPROG trial). DESIGN: Multicenter, two-arm, parallel-group, open-label randomized controlled trial. SETTING: 11 university hospital ambulatory surgery units in Paris, France. PARTICIPANTS: Patients scheduled for ambulatory surgery and able to be reached by telephone. INTERVENTION: A 7-item checklist designed to prevent late cancellation, available in five languages and two versions (for children and adults), was administered between 7 and 3 days before the planned date of surgery, by an automated phone system or a research assistant. The control group received standard management alone. MAIN OUTCOME MEASURES: Rate of cancellation on the day of surgery or the day before. RESULTS: The study population comprised 3900 patients enrolled between November 2012 and September 2013: 1950 patients were randomized to the checklist arm and 1950 patients to the control arm. The checklist was administered to 68.8% of patients in the intervention arm, 1002 by the automated phone system and 340 by a research assistant. The rate of late cancellation did not differ significantly between the checklist and control arms (109 (5.6%) vs. 113 (5.8%), adjusted odds ratio [95% confidence interval] = 0.91 [0.65-1.29], (p = 0.57)). Checklist administration revealed that 355 patients (28.0%) had not undergone tests ordered by the surgeon or anesthetist, and that 254 patients (20.0%) still had questions concerning the fasting state. CONCLUSIONS: A standardized pre-operative telephone checklist did not avoid late cancellations of ambulatory surgery but enabled us to identify several frequent causes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01732159. PMID- 26829481 TI - Soil Communities Promote Temporal Stability and Species Asynchrony in Experimental Grassland Communities. AB - BACKGROUND: Over the past two decades many studies have demonstrated that plant species diversity promotes primary productivity and stability in grassland ecosystems. Additionally, soil community characteristics have also been shown to influence the productivity and composition of plant communities, yet little is known about whether soil communities also play a role in stabilizing the productivity of an ecosystem. METHODOLOGY/PRINCIPAL FINDINGS: Here we use microcosms to assess the effects of the presence of soil communities on plant community dynamics and stability over a one-year time span. Microcosms were filled with sterilized soil and inoculated with either unaltered field soil or field soil sterilized to eliminate the naturally occurring soil biota. Eliminating the naturally occurring soil biota not only resulted in lower plant productivity, and reduced plant species diversity, and evenness, but also destabilized the net aboveground productivity of the plant communities over time, which was largely driven by changes in abundance of the dominant grass Lolium perenne. In contrast, the grass and legumes contributed more to net aboveground productivity of the plant communities in microcosms where soil biota had been inoculated. Additionally, the forbs exhibited compensatory dynamics with grasses and legumes, thus lowering temporal variation in productivity in microcosms that received the unaltered soil inocula. Overall, asynchrony among plant species was higher in microcosms where an unaltered soil community had been inoculated, which lead to higher temporal stability in community productivity. CONCLUSIONS/SIGNIFICANCE: Our results suggest that soil communities increase plant species asynchrony and stabilize plant community productivity by equalizing the performance among competing plant species through potential antagonistic and facilitative effects on individual plant species. PMID- 26829482 TI - Studies on Transcriptional Incorporation of 5'-N-Triphosphates of 5'-Amino-5' Deoxyribonucleosides. AB - In this study, several RNA polymerases were used for the first time to examine the possibility of transcriptional incorporation of 5'-N-triphosphates of 5' amino-5'-deoxyribonucleosides (5'NH NTPs). The T3, T7, Sp6 and T7 Y639F RNA polymerases were employed to show that the full-length transcript cannot be synthesized. The results suggest that the application of 5'NH NTPs could decrease transcription reaction rates. What is more, the modification of transcription conditions had no influence on the rate of 5'NH NTPs incorporation. Based on experimental data it is postulated that 5'NH NTPs can be used as potential transcription inhibitors. Our findings expand the knowledge on suitable uses of the 5'-N-triphosphates of 5'-amino-5'-deoxyribonucleoside and the exact mechanism of transcriptional inhibition. PMID- 26829483 TI - Attenuation of genotoxicity, oxidative stress, apoptosis and inflammation by rutin in benzo(a)pyrene exposed lungs of mice: plausible role of NF-kappaB, TNF alpha and Bcl-2. AB - BACKGROUND: Benzo(a)pyrene [B(a)P] is an environmental contaminant and potential carcinogenic agent that causes lung injuries which leads to lung cancer. Rutin, a well-known flavonoid present in various natural sources, possesses biological activities such as anti-oxidative and anti-inflammatory properties. The aim of this study was to evaluate the protective effects of rutin against B(a)P-induced genotoxicity, oxidative stress, apoptosis and inflammation in Swiss albino mice. METHODS: Pretreatment of rutin was given by oral gavage at doses of 40 and 80 mg/kg body weight (b.wt.) for 7 days before the administration of a single oral dose of B(a)P (125 mg/kg b.wt.). The ameliorative effect of rutin on oxidative stress, apoptotic and inflammatory markers in lung tissues and genotoxicity was studied using an alkaline unwinding assay and DNA fragmentation. RESULTS: B(a)P enhanced lipid peroxidation, xanthine oxidase, H2O2 generation and lactate dehydrogenase (LDH) activity; depleted activities of anti-oxidant enzymes and glutathione content; induced DNA strand breaks and fragmentation; disrupted normal histopathological architecture and also showed abnormal expression of NF kappaB, COX-2, IL-6, TNF-alpha and Bcl-2. Rutin pretreatment caused a significant reduction in lipid peroxidation and LDH activity; increased glutathione content; restored antioxidant enzyme activity; reduced DNA strand breaks and fragmentation; modulated the expression of inflammatory, and apoptotic markers and restored the histopathological structure. CONCLUSIONS: The findings of the present study supported the protective effect of rutin against B(a)P-induced lung toxicity and genotoxicity. PMID- 26829484 TI - Correction: Physical Activity Counselling during Pulmonary Rehabilitation in Patients with COPD: A Randomised Controlled Trial. PMID- 26829485 TI - Structural and functional attributes of malaria parasite diadenosine tetraphosphate hydrolase. AB - Malaria symptoms are driven by periodic multiplication cycles of Plasmodium parasites in human red blood corpuscles (RBCs). Malaria infection still accounts for ~600,000 annual deaths, and hence discovery of both new drug targets and drugs remains vital. In the present study, we have investigated the malaria parasite enzyme diadenosine tetraphosphate (Ap4A) hydrolase that regulates levels of signalling molecules like Ap4A by hydrolyzing them to ATP and AMP. We have tracked the spatial distribution of parasitic Ap4A hydrolase in infected RBCs, and reveal its unusual localization on the infected RBC membrane in subpopulation of infected cells. Interestingly, enzyme activity assays reveal an interaction between Ap4A hydrolase and the parasite growth inhibitor suramin. We also present a high resolution crystal structure of Ap4A hydrolase in apo- and sulphate- bound state, where the sulphate resides in the enzyme active site by mimicking the phosphate of substrates like Ap4A. The unexpected infected erythrocyte localization of the parasitic Ap4A hydrolase hints at a possible role of this enzyme in purinerigic signaling. In addition, atomic structure of Ap4A hydrolase provides insights for selective drug targeting. PMID- 26829487 TI - Molecular clustering in the cell: from weak interactions to optimized functional architectures. AB - Molecular components of the cell, such as lipids, proteins or RNA molecules, can associate through weak interactions and form clusters. A growing number of studies have shown that clustering of molecules is crucial for cell functions such as signal optimization and polarization. Clustering provides an intermediate level of organization between the molecular and cellular scales. Here we review recent studies focusing on how molecular clustering functions in different biological contexts, the potential importance of clustering for information processing, as well as the physical nature of cluster formation. We mainly refer to literature focusing on clusters within cell membranes, but also report findings on clusters in the cytosol, emphasizing their ubiquitous role. PMID- 26829486 TI - Feeding Behavior Modulates Biofilm-Mediated Transmission of Yersinia pestis by the Cat Flea, Ctenocephalides felis. AB - BACKGROUND: The cat flea, Ctenocephalides felis, is prevalent worldwide, will parasitize animal reservoirs of plague, and is associated with human habitations in known plague foci. Despite its pervasiveness, limited information is available about the cat flea's competence as a vector for Yersinia pestis. It is generally considered to be a poor vector, based on studies examining early-phase transmission during the first week after infection, but transmission potential by the biofilm-dependent proventricular-blocking mechanism has never been systematically evaluated. In this study, we assessed the vector competence of cat fleas by both mechanisms. Because the feeding behavior of cat fleas differs markedly from important rat flea vectors, we also examined the influence of feeding behavior on transmission dynamics. METHODOLOGY/PRINCIPAL FINDINGS: Groups of cat fleas were infected with Y. pestis and subsequently provided access to sterile blood meals twice-weekly, 5 times per week, or daily for 4 weeks and monitored for infection, the development of proventricular biofilm and blockage, mortality, and the ability to transmit. In cat fleas allowed prolonged, daily access to blood meals, mimicking their natural feeding behavior, Y. pestis did not efficiently colonize the digestive tract and could only be transmitted during the first week after infection. In contrast, cat fleas that were fed intermittently, mimicking the feeding behavior of the efficient vector Xenopsylla cheopis, could become blocked and regularly transmitted Y. pestis for 3-4 weeks by the biofilm-mediated mechanism, but early-phase transmission was not detected. CONCLUSIONS: The normal feeding behavior of C. felis, more than an intrinsic resistance to infection or blockage by Y. pestis, limits its vector competence. Rapid turnover of midgut contents results in bacterial clearance and disruption of biofilm accumulation in the proventriculus. Anatomical features of the cat flea foregut may also restrict transmission by both early-phase and proventricular biofilm-dependent mechanisms. PMID- 26829488 TI - Actomyosin-driven left-right asymmetry: from molecular torques to chiral self organization. AB - Chirality or mirror asymmetry is a common theme in biology found in organismal body plans, tissue patterns and even in individual cells. In many cases the emergence of chirality is driven by actin cytoskeletal dynamics. Although it is well established that the actin cytoskeleton generates rotational forces at the molecular level, we are only beginning to understand how this can result in chiral behavior of the entire actin network in vivo. In this review, we will give an overview of actin driven chiralities across different length scales known until today. Moreover, we evaluate recent quantitative models demonstrating that chiral symmetry breaking of cells can be achieved by properly aligning molecular scale torque generation processes in the actomyosin cytoskeleton. PMID- 26829490 TI - Divergent Reactivity via Cobalt Catalysis: An Epoxide Olefination. AB - Cobalt salts exert an unexpected and profound influence on the reactivity of epoxides with dimethylsulfoxonium methylide. In the presence of a cobalt catalyst, conditions for epoxide to an oxetane ring expansion instead deliver homoallylic alcohol products, corresponding to a two-carbon epoxide homologation/ring-opening tandem process. The observed reactivity change appears to be specifically due to cobalt salts and is broadly applicable to a variety of epoxides, retaining the initial stereochemistry. This transformation also provides operationally simple access to enantiopure homoallylic alcohols from chiral epoxides without use of organometallic reagents. Tandem epoxidation homologation of aldehydes in a single step is also demonstrated. PMID- 26829489 TI - Data-Limited Population-Status Evaluation of Two Coastal Fishes in Southern Angola Using Recreational Catch Length-Frequency Data. AB - Excessive truncation of a population's size structure is often identified as an important deleterious effect of exploitation, yet the effect on population persistence of size-structure truncation caused by exploitation is often not quantified due to data limitations. In this study, we estimate changes in eggs per recruit (EPR) using annual length-frequency samples over a 9 year period to assess persistence of the two most important recreational fishes in southern Angola: west coast dusky kob (Argyrosomus coronus) and leerfish (Lichia amia). Using a length- and age-structured model, we improve on an existing method to fit this type of model to length-frequency data and estimate EPR. The objectives of the methodological changes are to add flexibility and robustness to the approach for assessing population status in data-limited situations. Results indicate that dusky kob presents very low levels of EPR (5%-10% of the per recruit reproductive capacity in the absence of fishing) in 2013, whereas large inter-annual variability in leerfish estimates suggest caution must be applied when drawing conclusions about its exploitation status. Using simulated length frequency data with known parameter values, we demonstrate that recruitment decline due to overexploitation leads to overestimation of EPR values. Considering the low levels of EPR estimated for the study species, recruitment limitation is not impossible and true EPR values may be even lower than our estimates. It is, therefore, likely that management action, such as the creation of Marine Protected Areas, is needed to reconstitute the west coast dusky kob population. PMID- 26829491 TI - Accelerating Mineral Carbonation Using Carbonic Anhydrase. AB - Carbonic anhydrase (CA) enzymes have gained considerable attention for their potential use in carbon dioxide (CO2) capture technologies because they are able to catalyze rapidly the interconversion of aqueous CO2 and bicarbonate. However, there are challenges for widespread implementation including the need to develop mineralization process routes for permanent carbon storage. Mineral carbonation of highly reactive feedstocks may be limited by the supply rate of CO2. This rate limitation can be directly addressed by incorporating enzyme-catalyzed CO2 hydration. This study examined the effects of bovine carbonic anhydrase (BCA) and CO2-rich gas streams on the carbonation rate of brucite [Mg(OH)2], a highly reactive mineral. Alkaline brucite slurries were amended with BCA and supplied with 10% CO2 gas while aqueous chemistry and solids were monitored throughout the experiments (hours to days). In comparison to controls, brucite carbonation using BCA was accelerated by up to 240%. Nesquehonite [MgCO3.3H2O] precipitation limited the accumulation of hydrated CO2 species, apparently preventing BCA from catalyzing the dehydration reaction. Geochemical models reproduce observed reaction progress in all experiments, revealing a linear correlation between CO2 uptake and carbonation rate. Data demonstrates that carbonation in BCA-amended reactors remained limited by CO2 supply, implying further acceleration is possible. PMID- 26829492 TI - In Vitro Evaluation of the Effects of Multiple Oral Factors on Dental Implants Surfaces. AB - Presence of metal ions and debris resulting from corrosion processes of dental implants in vivo can elicit adverse tissue reactions, possibly leading to peri implant bone loss and eventually implant failure. This study hypothesized that the synergistic effects of bacterial biofilm and micromotion can cause corrosion of dental implants and release of metal ions in vivo. The goal is to simulate the oral environment where an implant will be exposed to a combination of acidic electrochemical environment and mechanical forces. Four conditions were developed to understand the individual and synergistic effects of mechanical forces and bacterial biofilm on the surface of dental implants; In condition 1, it was found that torsional forces during surgical insertion did not generate wear particle debris or metal ions. In condition 2, fatigue tests were performed in a wet environment to evaluate the effect of cyclic occlusal forces. The mechanical forces applied on the implants were able to cause implant fracture as well as surface corrosion features such as discoloration, delamination, and fatigue cracks. Immersion testing (condition 3) showed that bacteria ( Streptococcus mutans ) were able to create an acidic condition that triggered surface damage such as discoloration, rusting, and pitting. A novel testing setup was developed to understand the conjoint effects of micromotion and bacterial biofilm (condition 4). Surface damage initiated by acidic condition due to bacteria (condition 3), can be accelerated in tandem with mechanical forces through fretting-crevice corrosion. Permanent damage to surface layers can affect osseointegration and deposition of metal ions in the surrounding tissues can trigger inflammation. PMID- 26829493 TI - Hydrogel with Aligned and Tunable Pore Via "Hot Ice" Template Applies as Bioscaffold. AB - An aligned hydrogel with tunable macropore size via hot ice template is described, which exhibits a high porosity, large pore size, easily modified surface, high survival rate as well as a linear arrangement of NIH3T3 cells. PMID- 26829494 TI - Intraoperative goal-directed hemodynamic management in free tissue transfer for head and neck cancer. AB - BACKGROUND: The purpose of this study was to determine the effect of algorithmic physiologic management on patients undergoing head and neck free tissue transfer and reconstruction. METHODS: Ninety-four adult patients were randomized to treatment and control groups. The blood pressure of the control group was managed consistent with contemporary standards. The treatment group was managed using an algorithm based on blood pressure and calculated physiologic values derived from arterial waveform analysis. Primary outcome was intensive care unit (ICU) length of stay. RESULTS: ICU length of stay was decreased in the treatment group (33.7 vs 58.3 hours; p = .026). The complication rate was not increased in the treatment group. CONCLUSION: The goal-directed hemodynamic management algorithm decreased the ICU length of stay. Judicious use of vasoactive drugs and goal directed fluid administration has a role in improving perioperative outcomes for patients undergoing head and neck free tissue transfer. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1974-E1980, 2016. PMID- 26829495 TI - Mitral Valve Repair via a Minithoracotomy in a Patient With Pectus Excavatum. AB - Cardiac surgery in patients with pectus excavatum is challenging because of the difficulty associated with achieving optimal surgical exposure and postoperative sternal fixation by using standard instruments. To solve these problems, mitral valve repair was performed via a right minithoracotomy in a 48-year-old man with severe mitral valve regurgitation and pectus excavatum. With the use of conventional median sternotomy, an optimal surgical field was difficult to achieve because of his thoracic deformity. Therefore, surgical fixation via right minithoracotomy using particular equipment was performed. Using right minithoracotomy, we could obtain an optimal surgical field better than that with median sternotomy, and the patient's mitral valve regurgitation was fixed properly. This approach provides mitral valve exposure advantages as well as cosmetic satisfaction. PMID- 26829496 TI - Possible role of plant volatiles in tolerance against huanglongbing in citrus. AB - Volatile organic compounds (VOC) play an important role in protecting plants from insect and pathogen attack. In this study, we investigated the leaf volatile profiles of 14 citrus varieties. The VOC in citrus leaves were extracted with n hexane and analyzed using gas chromatography-mass spectrometry (GC-MS). Overall, 4six volatile compounds were identified in the n-hexane extract from citrus leaves. Most of the detected compounds belonged to 3 main groups (monoterpenes, sesquiterpenes, and aliphatic aldehydes). Principle component analysis was used to examine the relative distribution of the studied varieties to each other. Interestingly, volatile profiles of varieties that are tolerant to Candidatus Liberibacter asiaticus (CLas) were different from those of the susceptible ones. Tolerant and moderately-tolerant cultivars contained relatively higher amounts of volatiles than susceptible varieties. In addition, tolerant varieties were also higher in specific compounds which are known for their antimicrobial activities. These compounds include Aldehydes (undecanal, neral, geranial, and citronellal) and some monoterpenes such as linalool, d-limonene, myrcene, alpha- and beta- phellandrene. In addition, some sesquiterpene compounds including t caryophellene, gamma-elemene, beta-elemene, germacrene D, and geranyl acetate were higher in tolerant and moderately tolerant cultivars. Severinia buxifolia which is known for its tolerance to CLas and many other pathogens contained higher levels of santalenes and coumarins. Our results indicated that citrus leaf volatiles might play a role in citrus tolerance to CLas. The results of this study may help in understanding of the mechanism of citrus tolerance against CLas. PMID- 26829497 TI - ClassTR: Classifying Within-Host Heterogeneity Based on Tandem Repeats with Application to Mycobacterium tuberculosis Infections. AB - Genomic tools have revealed genetically diverse pathogens within some hosts. Within-host pathogen diversity, which we refer to as "complex infection", is increasingly recognized as a determinant of treatment outcome for infections like tuberculosis. Complex infection arises through two mechanisms: within-host mutation (which results in clonal heterogeneity) and reinfection (which results in mixed infections). Estimates of the frequency of within-host mutation and reinfection in populations are critical for understanding the natural history of disease. These estimates influence projections of disease trends and effects of interventions. The genotyping technique MLVA (multiple loci variable-number tandem repeats analysis) can identify complex infections, but the current method to distinguish clonal heterogeneity from mixed infections is based on a rather simple rule. Here we describe ClassTR, a method which leverages MLVA information from isolates collected in a population to distinguish mixed infections from clonal heterogeneity. We formulate the resolution of complex infections into their constituent strains as an optimization problem, and show its NP completeness. We solve it efficiently by using mixed integer linear programming and graph decomposition. Once the complex infections are resolved into their constituent strains, ClassTR probabilistically classifies isolates as clonally heterogeneous or mixed by using a model of tandem repeat evolution. We first compare ClassTR with the standard rule-based classification on 100 simulated datasets. ClassTR outperforms the standard method, improving classification accuracy from 48% to 80%. We then apply ClassTR to a sample of 436 strains collected from tuberculosis patients in a South African community, of which 92 had complex infections. We find that ClassTR assigns an alternate classification to 18 of the 92 complex infections, suggesting important differences in practice. By explicitly modeling tandem repeat evolution, ClassTR helps to improve our understanding of the mechanisms driving within-host diversity of pathogens like Mycobacterium tuberculosis. PMID- 26829498 TI - Using Zebrafish to Implement a Course-Based Undergraduate Research Experience to Study Teratogenesis in Two Biology Laboratory Courses. AB - A course-based undergraduate research experience (CURE) spanning three semesters was introduced into freshman and sophomore biology classes, with the hypothesis that participation in a CURE affects skills in research, communication, and collaboration, which may help students persist in science. Student research projects were centered on the hypothesis that nicotine and caffeine exposure during early development affects gastrulation and heart development in zebrafish. First, freshmen generated original data showing distinct effects of embryonic nicotine and caffeine exposure on zebrafish heart development and function. Next, Cell Biology laboratory students continued the CURE studies and identified novel teratogenic effects of nicotine and caffeine during gastrulation. Finally, new freshmen continued the CURE research, examining additional toxicant effects on development. Students designed new protocols, made measurements, presented results, and generated high-quality preliminary data that were studied in successive semesters. By implementing this project, the CURE extended faculty research and provided a scalable model to address national goals to involve more undergraduates in authentic scientific research. In addition, student survey results support the hypothesis that CUREs provide significant gains in student ability to (1) design experiments, (2) analyze data, and (3) make scientific presentations, translating into high student satisfaction and enhanced learning. PMID- 26829499 TI - Reply: Secreted Brain-Derived Neurotrophic Factor and Asthma Severity. PMID- 26829500 TI - Secreted Brain-Derived Neurotrophic Factor and Asthma Severity. PMID- 26829502 TI - Characterization of a Squaraine/Chitosan System for Photodynamic Therapy of Cancer. AB - In this work, a squaraine dye CS5 was characterized and evaluated for its potential in photodynamic therapy. The studies were performed in ethanol and also in a powdered biopolymer, in this case chitosan. Ground state absorption, absolute fluorescence quantum yields, fluorescence lifetimes, and transient absorption were determined in order to evaluate the advantage of adsorbing the dye onto a biopolymer. Several concentrations of the dye, adsorbed onto chitosan, were prepared in order to evaluate the concentration effect on the photophysical parameters under study. A remarkable increase in the fluorescence quantum yield and lifetimes was detected when compared with the dye in solution. Also, a very clear dependence of the fluorescence quantum yield on the concentration range was found. A lifetime distribution analysis of these systems fluorescence evidenced the entrapment of the dye onto the chitosan environment with a monoexponential decay which corresponds to the monomer emission in slightly different environments. The transient absorption spectrum was obtained without sensitization indicating the existence of a triplet state which takes special importance in the generation of phototoxic species namely singlet oxygen. The subcellular localization of a photosensitizer is critical for efficient photoinduced cell death, in this way, colocalization studies were performed within HeLa cell line (human cervical carcinoma) through confocal microscopy. Toxicity in the dark and phototoxicity of CS5 were also evaluated for the same cellular model. PMID- 26829503 TI - Predictive factors of relapse in low-risk gestational trophoblastic neoplasia patients successfully treated with methotrexate alone. AB - BACKGROUND: Patients with 2000 FIGO low-risk gestational trophoblastic neoplasia are commonly treated with single-agent chemotherapy. Methotrexate is widely used in this indication in Europe. Analysis of relapse after treatment and identification of factors associated with relapse would help understand their potential impacts on 2000 FIGO score evolution and chemotherapy management of gestational trophoblastic neoplasia patients. OBJECTIVE: This retrospective study analyzes the predictive factors of relapse in low-risk gestational trophoblastic neoplasia patients whose hormone chorionic gonadotropin (hCG) normalized with methotrexate alone. STUDY DESIGN: Between 1999 and 2014, 993 patients with gestational trophoblastic neoplasia were identified in the French Trophoblastic Disease Reference Center database, of which 465 were low-risk patients whose hCG normalized with methotrexate alone. Using univariate and multivariate analysis we identified significant predictive factors for relapse after methotrexate. The Kaplan-Meier method was used to plot the outcome of patients. RESULTS: The 5-year recurrence rate of low-risk gestational trophoblastic neoplasia patients whose hCG normalized with methotrexate alone was 5.7% (confidence interval [IC], 3.86 8.46). Univariate analysis identified an antecedent pregnancy resulting in a delivery (HR = 5.96; 95% CI, 1.40-25.4, P = .016), a number of methotrexate courses superior to 5 courses (5-8 courses vs 1-4: HR = 6.19; 95% CI, 1.43-26.8, P = .015; 9 courses and more vs 1-4: HR = 6.80; 95% CI, 1.32-35.1, P = .022), and hCG normalization delay centered to the mean as predictive factors of recurrence (HR = 1.27; 95% CI, 1.09-1.49, P = .003). Multivariate analysis confirmed the type of antecedent pregnancy and the number of methotrexate courses as independent predictive factors of recurrence. A low-risk gestational trophoblastic neoplasia arising after a normal delivery had an 8.66 times higher relapse risk than that of a postmole gestational trophoblastic neoplasia (95% CI, 1.98-37.9], P = .0042). A patient who received 5-8 courses of methotrexate had a 6.7 times higher relapse risk than a patient who received 1-4 courses (95% CI, 1.54-29.2, P = .011). A patient who received 9 courses or more had an 8.1 times higher relapse risk than a patient who received 1-4 courses of methotrexate (95% CI, 1.54-42.6, P = .014). CONCLUSION: Low-risk gestational trophoblastic neoplasia following a delivery and patients who need more than 4 courses of methotrexate to normalization are at a higher risk of relapse than other low-risk patients. Allotting a higher score to the "antecedent pregnancy" FIGO item should be considered for postdelivery gestational trophoblastic neoplasia. Further analysis of the need for consolidation courses is warranted. PMID- 26829504 TI - Severe maternal morbidity in a large cohort of women with acute severe intrapartum hypertension. AB - BACKGROUND: Hypertensive diseases of pregnancy are associated with severe maternal morbidity and remain common causes of maternal death. Recently, national guidelines have become available to aid in recognition and management of hypertension in pregnancy to reduce morbidity and mortality. The increased morbidity related to hypertensive disorders of pregnancy is presumed to be associated with the development of severe hypertension. However, there are few data on specific treatment or severe maternal morbidity in women with acute severe intrapartum hypertension as opposed to severe preeclampsia. OBJECTIVE: The study aimed to characterize maternal morbidity associated with women with acute severe intrapartum hypertension, and to determine whether there was an association between various first-line antihypertensive agents and posttreatment blood pressure. STUDY DESIGN: This retrospective cohort study of women delivering between July 2012 and August 2014 at 15 hospitals participating in the California Maternal Quality Care Collaborative compared women with severe intrapartum hypertension (systolic blood pressure >160 mm Hg or diastolic blood pressure >105 mm Hg) to women without severe hypertension. Hospital Patient Discharge Data and State of California Birth Certificate Data were used. Severe maternal morbidity using the Centers for Disease Control and Prevention criteria based on International Classification of Diseases-9 codes was compared between groups. The efficacy of different antihypertensive medications in meeting the 1-hour posttreatment goal was determined. Statistical methods included distribution appropriate univariate analyses and multivariate logistic regression. RESULTS: There were 2252 women with acute severe intrapartum hypertension and 93,650 women without severe hypertension. Severe maternal morbidity was significantly more frequent in the women with severe hypertension (8.8%) compared to the control women (2.3%) (P < .0001). Severe maternal morbidity rates did not increase with increasing severity of blood pressures (P = .90 for systolic and .42 for diastolic). There was no difference in severe maternal morbidity between women treated (8.6%) and women not treated (9.5%) (P = .56). Antihypertensive treatment rates were significantly higher in hospitals with a level IV neonatal intensive care unit (85.8%) compared to a level III neonatal intensive care unit (80.2%) (P < .001), and in higher-volume hospitals (84.5%) compared to lower-volume hospitals (69.1%) (P < .001). Severe maternal morbidity rates among severely hypertensive women were significantly higher in hospitals with level III neonatal intensive care unit level compared to hospitals with a level IV neonatal intensive care unit (10.6% vs 5.7%, respectively; P < .001), and significantly higher in low-delivery volume hospitals compared to high-delivery volume hospitals (15.5% vs 7.6%, respectively; P < .001). Only 53% of women treated with oral labetalol as first-line medication met the posttreatment goal of nonsevere hypertension, significantly less than those treated with intravenous hydralazine, intravenous labetalol, or oral nifedipine (68%, 71%, and 82%, respectively) (P = .001). Severe intrapartum hypertension remained untreated in 17% of women. CONCLUSION: Women with acute severe intrapartum hypertension had a significantly higher risk of severe maternal morbidity compared to women without severe hypertension. Significantly lower antihypertensive treatment rates and higher severe maternal morbidity rates were seen in lower-delivery volume hospitals. PMID- 26829505 TI - Reply. PMID- 26829506 TI - Prenatal stress and newborn telomere length. AB - BACKGROUND: The developmental origin of the health and disease hypothesis is based on the premise that many chronic diseases have their roots in fetal development. Specifically, maternal stress during pregnancy is associated with altered fetal development and many adverse long-term health outcomes. Although the mechanisms underlying this effect are currently unclear, at the cellular level 1 possible mediator is the regulation of telomere length. Telomere dynamics appear to play a role in disease progression, and an adverse intrauterine environment may contribute in the establishment of short telomeres in newborns. In accordance with this, it was recently reported that prenatal stress is significantly associated with shorter mean newborn telomere length. However, this finding has yet to be replicated, and currently we know nothing about whether different size classes of telomeres within the telomere length distribution are differentially affected by prenatal stress. Examining telomere length frequency distributions is important, because the shortest telomeres in the distribution appear to be the most indicative of telomere dysfunction and thus the best predictors of mortality and morbidity in humans. OBJECTIVE: We investigated the effects of intrauterine exposure to maternal stress over the whole course of gestation on newborn mean telomere length and telomere length frequency distributions. STUDY DESIGN: We conducted a prospective cohort study of 24 mother newborn dyads at an urban teaching hospital. Pregnant women with nonanomalous, uncomplicated pregnancies were recruited and assessed in the third trimester of gestation. Maternal psychosocial stress was quantified using the Holmes and Rahe Stress Scale and categorized as high stress (>=300 points) or low stress (<=299 points) exposure. Newborn telomere length was measured from cord blood at delivery using the Telomere Restriction Fragment assay. RESULTS: We found a significant negative association between maternal stress and newborn telomere length (beta = -0.463, P = 0.04). Newborns whose mothers experienced a high level of stress during pregnancy had significantly shorter telomere length (6.98 +/- 0.41 kb) compared to newborns of mothers with low stress (8.74 +/- 0.24 kb; t = 3.99, P = .003). Moreover, the difference in newborn telomere length between high stress and low-stress mothers was due to a shift in the telomere length distribution, with the high-stress group showing an underrepresentation of longer telomeres and an over-representation of shorter telomeres. CONCLUSION: Our findings replicate those of other recent studies and also show, for the first time, that the prenatal stress-associated difference in newborn mean telomere length is due to a shift in the overall telomere distribution. PMID- 26829507 TI - Obesity and endometrial hyperplasia and cancer in premenopausal women: A systematic review. AB - OBJECTIVE: To systematically review the literature on the association between obesity and endometrial hyperplasia or cancer in premenopausal women. DATA SOURCES: We searched the bibliographic databases MEDLINE, EMBASE, PubMed, and CINAHL (inception to May 5, 2015), and checked reference lists of included studies and systematic reviews. STUDY ELIGIBILITY CRITERIA: Studies of more than 50 women with endometrial pathology diagnosed during premenopause that reported on obesity as a risk factor were eligible. STUDY APPRAISAL AND SYNTHESIS METHODS: Study identification and data extraction were independently performed by 2 authors. Where possible, data were pooled in a generic inverse variance forest plot. Heterogeneity was reported using the I(2) statistic. RESULTS: Nine case control studies of moderate quality were included. Quantitative analysis of 5 studies showed a dose-response relationship of body mass index and increased risk of endometrial cancer. For studies of women with body mass index of >=25, the pooled odds ratio was 3.85 (95% confidence interval 2.53-5.84); body mass index of >=30 was 5.25 (4.00-6.90); and body mass index of >=40 was 19.79 (11.18 35.03). CONCLUSION: Body mass index is a consistent and leading risk factor for endometrial complex hyperplasia or cancer in premenopausal women. Body mass index should be considered when deciding to assess the endometrium in symptomatic premenopausal women. PMID- 26829508 TI - 17-Hydroxyprogesterone caproate (17OHP-C) coverage among eligible women delivering at 2 North Carolina hospitals in 2012 and 2013: A retrospective cohort study. AB - BACKGROUND: Although a weekly injection of 17-hydroxyprogestone caproate is recommended for preventing recurrent preterm birth, clinical experience in North Carolina suggested that many eligible patients were not receiving the intervention. OBJECTIVE: Our study sought to assess how well practices delivering at 2 major hospitals were doing in providing access to 17-hydroxyprogesterone caproate treatment for eligible patients. STUDY DESIGN: This retrospective cohort analysis studied all deliveries occurring between January 1, 2012, and December 31, 2013, at 2 large hospitals in North Carolina. Women were included if they had a singleton pregnancy and history of a prior spontaneous preterm birth. We extracted demographic, payer, and medical information on each pregnancy, including whether women had been offered, accepted, and received 17 hydroxyprogesterone caproate. Our outcome of 17-hydroxyprogesterone caproate coverage was defined as documentation of >=1 injection of the drug. RESULTS: Over the 2-year study period, 1216 women with history of a prior preterm birth delivered at the 2 study hospitals, of which 627 were eligible for 17 hydroxyprogesterone caproate eligible after medical record review. Only 296 of the 627 eligible women (47%; 95% confidence interval, 43-51%) received >=1 dose of the drug. In multivariable analysis, hospital of delivery, later presentation for prenatal care, fewer prenatal visits, later gestation of prior preterm birth, and having had a term delivery immediately before the index pregnancy were all associated with failed coverage. Among those women who were "covered," the median number of 17-hydroxyprogesterone caproate injections was 9 (interquartile range, 4-15), with 84 of 296 charts (28%) not having complete information on the number of doses. CONCLUSION: Even under our liberal definition of coverage, less than half of eligible women received 17-hydroxyprogesterone caproate in this sample. Low overall use suggests that there is opportunity for improvement. Quality improvement strategies, including population-based measurement of 17 hydroxyprogesterone caproate coverage, are needed to fully implement this evidence-based intervention to decrease preterm birth. PMID- 26829509 TI - Anti-hemorrhagic effect of prophylactic tranexamic acid in benign hysterectomy-a double-blinded randomized placebo-controlled trial. AB - BACKGROUND: Hysterectomy is one of the most frequently performed major gynecological surgical procedures. Even when the indication for the procedure is benign, relatively high complication rates have been reported. Perioperative bleeding seems to represent the most common cause of complications and in 2004, 8% of all women in Denmark undergoing benign hysterectomy experienced a bleeding complication. Tranexamic acid is an antifibrinolytic agent that has shown to effectively reduce bleeding complications within other surgical and medical areas. However, knowledge about the drug's effect in relation to benign hysterectomy is still missing. OBJECTIVE: To investigate the antihemorrhagic effect of prophylactic tranexamic acid in elective benign hysterectomy. STUDY DESIGN: A double-blinded randomized placebo-controlled trial was conducted at 4 gynecological departments in Denmark from April 2013 to October 2014. A total of 332 women undergoing benign abdominal, laparoscopic, or vaginal hysterectomy were included in the trial, randomized to either 1 g of intravenous tranexamic acid or placebo at start of surgery. Chi-square test and Student t test statistical analyses were applied. RESULTS: The primary outcome of intraoperative total blood loss was reduced in the group treated with tranexamic acid compared to the placebo group when estimated both subjectively by the surgeon and objectively by weight (98.4 mL vs 134.8 mL, P = .006 and 100.0 mL vs 166.0 mL, P = .004). The incidence of blood loss >=500 mL was also significantly reduced (6 vs 21, P = .003), as well as the use of open-label tranexamic acid (7 vs 18, P = .024). Furthermore, the risk of reoperations owing to postoperative hemorrhage was significantly reduced in the tranexamic acid group compared to the placebo group (2 vs 9, P = .034). This corresponds to an absolute risk reduction of 4.2% and number needed to treat of 24. No incidence of thromboembolic events or death was observed in any of the groups. CONCLUSION: The results support the hypothesis that prophylactic treatment with tranexamic acid reduces the overall total blood loss, the incidence of substantial blood loss, and the need for reoperations owing to postoperative hemorrhage in relation to benign hysterectomy. No incidences of serious adverse events occurred. Thus, tranexamic acid should be considered as a prophylactic treatment prior to elective benign hysterectomy. PMID- 26829511 TI - Cerebral palsy: Causes, pathways, and the role of genetic variants. PMID- 26829510 TI - Obesogens: an emerging threat to public health. AB - Endocrine disrupting chemicals (EDCs) are defined as exogenous chemicals, or mixtures of chemicals, that can interfere with any aspect of hormone action. The field of endocrine disruption is historically rooted in wildlife biology and reproductive endocrinology where EDCs are demonstrated contributors to infertility, premature puberty, endometriosis, and other disorders. Recently, EDCs have been implicated in metabolic syndrome and obesity. Adipose tissue is a true endocrine organ and, therefore, an organ that is highly susceptible to disturbance by EDCs. A subset of EDCs, called "obesogens," promote adiposity by altering programming of fat cell development, increasing energy storage in fat tissue, and interfering with neuroendocrine control of appetite and satiety. Obesity adds more than $200 billion to US healthcare costs and the number of obese individuals continues to increase. Hence, there is an urgent, unmet need to understand the mechanisms underlying how exposures to certain EDCs may predispose our population to be obese. In this review, we discuss the history of obesogen discovery from its origins in reproductive biology to its latest role in the transgenerational inheritance of obesity in mice. We discuss the development of adipose tissue in an embryo, maintenance of adipocyte number in adults, how EDC disruption programs stem cells to preferentially make more adipocytes, the mechanisms by which chemicals can permanently alter the germline epigenome, and whether there are barriers to EDCs in the gametes. PMID- 26829512 TI - Cytokines in noninvasively obtained amniotic fluid as predictors of fetal inflammatory response syndrome. AB - BACKGROUND: In patients with preterm premature rupture of membranes, intrauterine inflammation and/or infection is frequently present, can lead to fetal inflammatory response syndrome, and is associated with adverse neonatal outcome. Clinical decision making requires balancing the potential benefits of pregnancy prolongation against the risk of intrauterine infection. Diagnostic tests in maternal serum are of moderate prediction value and amniocentesis is an invasive procedure. Therefore, markers obtained noninvasively would be helpful in patients with expectant management. OBJECTIVES: To determine the predictive values of amniotic fluid interleukin-6 and tumor necrosis factor-alpha in vaginal secretions for fetal inflammatory response syndrome and/or histologic funisitis and for adverse neonatal outcome in patients with preterm premature rupture of membranes. STUDY DESIGN: In this prospective multicenter case-control study, vaginal secretions were sampled daily with a noninvasive method from 99 women with preterm premature rupture of membranes and expectant management. Amniotic fluid interleukin-6 and tumor necrosis factor-alpha were measured by 2 different immunoassays (an automated chemiluminescent enzyme immunoassay and a lateral flow immunoassay). After delivery, patients were divided into a control or a fetal inflammatory response syndrome group according to neonatal interleukin-6 in cord plasma and/or the presence of funisitis. Univariate and multivariate regression analyses were performed and prediction models were developed by calculating receiver operating characteristic curves. RESULTS: Gestational age at delivery was lower and latency period was longer in the fetal inflammatory response syndrome group compared to the control group. The strongest risk factor for composite adverse neonatal outcome was fetal inflammatory response syndrome (odds ratio, 2.48; confidence interval, 1.40-4.38). The median concentrations of amniotic fluid interleukin-6 and tumor necrosis factor-alpha in vaginal secretions were significantly higher in the fetal inflammatory response group compared to the control group in both immunoassays (P < .001). The area under the curve of the clinical reference model (including common clinical parameters) was 0.66. Adding interleukin-6 and tumor necrosis factor-alpha into the model improved the area under the curve to 0.92 (in both assays, interleukin-6 IMMULITE and QuickLine); 0.87 (tumor necrosis factor-alpha IMMULITE) and 0.94 (tumor necrosis factor-alpha QuickLine), respectively. CONCLUSION: The strongest risk factor for worse neonatal outcome (composite neonatal outcome) was fetal inflammatory response syndrome. Amniotic fluid interleukin-6 and tumor necrosis factor-alpha seem to be good predictors for fetal inflammatory response syndrome and for histologic funisitis and may improve the clinical management of patients with preterm premature rupture of membranes. The noninvasive technique of sampling amniotic fluid from vaginal secretions facilitates daily measurements and bedside assessment of cytokines and is in this respect preferable to invasive amniocentesis. PMID- 26829513 TI - Bangle (Zingiber purpureum) Improves Spatial Learning, Reduces Deficits in Memory, and Promotes Neurogenesis in the Dentate Gyrus of Senescence-Accelerated Mouse P8. AB - Bangle (Zingiber purpureum) is a tropical ginger that is used as a spice in Southeast Asia. Phenylbutenoid dimers isolated from Bangle have exhibited neurotrophic effects in primary cultured rat cortical neurons and PC12 cells. Furthermore, chronic treatment with phenylbutenoid dimers enhances hippocampal neurogenesis in olfactory bulbectomized mice. In this study, we investigated the effects of Bangle extract on behavior and hippocampal neurogenesis in vivo. SAMP8 mice, which are an established model for accelerated aging, with age-related learning and memory impairments, were given a Bangle-containing diet for 1 month, and subsequent behavioral tests and immunohistochemistry for Ki67, a proliferating cell marker, were performed. We found that the Bangle-containing diet improved spatial learning and memory deficits in the Morris water maze and significantly increased the numbers of Ki67-positive cells in the dentate gyrus of the SAMP8 mice. In addition, the Bangle extract exhibited a neurotrophin-like activity as indicated by the induction of neurite sprouting in PC12 cells. Our results suggest that Bangle is beneficial for the prevention of age-related progression of cognitive impairment. PMID- 26829514 TI - Weight-related and analytical maternal factors in gestational diabetes to predict birth weight and cord markers of diabetic fetopathy. AB - OBJECTIVE: The objective was to determine the value of clinical and analytical maternal factors to predict birth weight and umbilical cord biochemical markers of diabetic fetopathy. METHODS: Prospective evaluation of gestational diabetes pregnancies (n = 50). Maternal weight-related clinical and analytical factors were collected during pregnancy. After birth, an umbilical cord sample was taken. RESULTS: Univariate linear regression analysis showed relationship between maternal weight, glycated hemoglobin (HbA1c) and insulin-like growth factor 1 (IGF1) with birth weight percentile. A significant association was found between maternal weight and cord insulin and C-peptide. Maternal HbA1c, leptin and insulin during pregnancy showed a positive linear association to cord leptin, insulin and C-peptide. In multivariate analysis models, final maternal BMI showed an independent positive association with cord C-peptide. CONCLUSIONS: Maternal weight-related and analytical parameters show diagnostic value to birth weight and cord markers. PMID- 26829515 TI - Hookah and Cigarette Smoking Among African American College Students: Implications for Campus Risk Reduction And Health Promotion Efforts. AB - OBJECTIVE: To identify individual and institutional risks and protections for hookah and cigarette smoking among African American (AA) college students. PARTICIPANTS: AA college students (N = 1,402; mean age = 20, range = 18-24 years; 75% female) who completed the Fall 2012 American College Health Association National College Health Assessment II. METHODS: Respondents were stratified into 4 mutually exclusive groups by last-30-day smoking status: cigarette-only use (5.1%), hookah-only use (5.9%), dual use (2.4%), and nonuse (86.6%). Multinomial logistic regression models identified the relative odds of exclusive and dual hookah and cigarette smoking. RESULTS: Current hookah and cigarette smoking rates were comparably low. Age, gender identity, current substance use, interest in tobacco use information, and student population prevailed as risks and protections for hookah and cigarette smoking. CONCLUSIONS: Campus health promotion campaigns may need to tailor messages to AA students, particularly those who use substances, to underscore the health risks of hookah and cigarette smoking. PMID- 26829516 TI - A new method to identify hydrolytic degradants in drug substances with UPLC-MS using 18O-labelled water. AB - Drug substances are susceptible to many different degradation pathways due to diverse nature of the molecule structures. Hydrolysis is one of the most common reactions seen for drug substances and drug products since water is ubiquitously present either as moisture or included in some formulations such as parenteral products. The hydrolytic degradation of fluticasone propionate, duloxetine and amlodipine was studied in this work using (18)O-labelled water with UPLC-MS. The structural proposals of the degradants are based solely on the molecular mass of the degradants with enhanced certainty by corresponding results from (18)O labeling experiments. The advantage of using (18)O labeling experiments is the extra information from knowing whether a water molecule is incorporated into a degradant or not, therefore enabling either confirmation or rejection of a proposed molecular structure. PMID- 26829517 TI - Application of an intracellular assay for determination of tenofovir-diphosphate and emtricitabine-triphosphate from erythrocytes using dried blood spots. AB - This communication describes the application of an existing intracellular methodology to the quantitation of tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) from erythrocytes using dried blood spots (DBS). Concentrations were determined from a 3mm DBS punch extracted into a 70:30 methanol:water solution (lysed cellular matrix). This extraction solution was then subjected to a previously validated analytical procedure for lysed cellular matrix. Experiments for DBS validation used replicate samples from study participants to demonstrate acceptable reproducibility with spot volumes ranging from 10-50 MUL and punch location either from the edge or center of the spot. Analysis of paired DBS with purified red blood cells showed that a 3mm DBS punch contained an average of 11.9 million cells for the observed hematocrit range of the participants (35-50%). Numerous stability tests were completed showing that whole blood in an EDTA vacutainer could sit for 24h at room temperature prior to spotting, and DBS could remain at room temperature for up to five days including shipment at ambient using 2-days delivery. DBS stability in storage was acceptable up to 18 months at -20 degrees C or -80 degrees C and DBS could undergo 4 Freeze/Thaw cycles. The described method was applied to HIV prophylaxis studies, demonstrating powerful associations with HIV acquisition through its ability to discriminate gradients of adherence. PMID- 26829518 TI - Caffeic acid phenethyl ester exhibiting distinctive binding interaction with human serum albumin implies the pharmacokinetic basis of propolis bioactive components. AB - Caffeic acid phenethyl ester (CAPE), as one of the major bioactive components present in propolis, exhibits versatile bioactivities, especially for its potent cytotoxic effects on several cancer cell models. To understand the pharmacokinetic characteristics of CAPE, the binding interaction between CAPE and human serum albumin (HSA) was investigated in vitro using multiple spectroscopic methods and molecular docking. The results reveal that CAPE exhibits a distinctive binding interaction with HSA comparing with other propolis components. The association constant K(A) (L mol(-1)) of the binding reaches 10(6) order of magnitude, which is significantly stronger than the other components of propolis. Based on the theory of fluorescence resonance energy transfer, the binding distance was calculated as 5.7 nm, which is longer than that of the other components of propolis. The thermodynamic results indicate that the binding is mainly driven by hydrogen bonds and van der Waals force. The docking and drugs (warfarin and ibuprofen) competitive results show that CAPE is located in the subdomain IIA (Sudlow's site I, FA7) of HSA, and Gln196 and Lys199 contribute to the hydrogen bonds. Circular dichroism spectra suggest an alteration of the secondary structure of HSA due to its partial unfolding in the presence of CAPE. PMID- 26829519 TI - In Vitro and In Vivo Antileishmanial Activities of Pistacia vera Essential Oil. AB - This study aims to evaluate the in vitro and in vivo antileishmanial activities of Pistacia vera essential oil and compare their efficacy with a reference drug, meglumine antimoniate (Glucantime(r)). This essential oil (0-100 ug/mL) was evaluated in vitro against the intracellular amastigote forms of Leishmania tropica (MHOM/IR/2002/Mash2) and then tested on cutaneous leishmaniasis of male BALB/c mice by Leishmania major (MRHO/IR/75/ER). In the in vitro assay, it could be observed that P. vera essential oil significantly (p < 0.05) inhibited the growth rate of amastigote forms (IC50 of 21.3 +/- 2.1 ug/mL) in a dose-dependent response compared with the control drug. Meglumine antimoniate also demonstrated antileishmanial effects with an IC50 value of 44.6 +/- 2.5 ug/mL for this clinical stage. In the in vivo assay, the results indicated that 30 mg/mL of the essential oil had potent suppression effects on cutaneous leishmaniasis in BALB/c mice (87.5% recovery), while 10 and 20 mg/mL of the essential oil represented the suppression effects as weak to intermediate. The mean diameter of the lesions decreased about 0.11 and 0.27 cm after the treatment of the subgroups with the essential oil concentrations of 10 and 20 mg/mL, respectively. In contrast, in the subgroup treated with the essential oil concentration of 30 mg/mL, the mean diameter of the lesions decreased about 0.56 cm. In the control subgroups, the mean diameter of the lesions increased to 1.01 cm. The main components of P. vera essential oil were limonene (26.21%), alpha-pinene (18.07%), and alpha-thujene (9.31%). It was also found that P. vera essential oil had no significant cytotoxic effect on J774 cells. The present study found that P. vera essential oil showed considerable in vitro and in vivo effectiveness against L. tropica and L. major compared to the reference drug. These findings also provided the scientific evidence that natural plants could be used in traditional medicine for the prevention and treatment of cutaneous leishmaniasis. PMID- 26829520 TI - Characterization of the Anticoagulative Constituents of Angelicae Sinensis Radix and Their Metabolites in Rats by HPLC-DAD-ESI-IT-TOF-MSn. AB - Angelicae Sinensis Radix is commonly used in traditional Chinese medicine. Pharmacological studies show that Angelicae Sinensis Radix has clear anticoagulant activity. Therefore, in this study, the anticoagulant activity of crude Angelicae Sinensis Radix extracts was investigated by measuring the thrombin times of the extracts. The results revealed that the petroleum ether soluble fraction of Angelicae Sinensis Radix exhibited significant anticoagulant activity in vitro, and 26 compounds were characterized by high-performance liquid chromatography with diode array detection combined with electrospray ionization ion trap time-of-flight multistage mass spectrometry. In addition, 5 prototype constituents, 24 in vivo metabolites in rat urine and 7 prototype constituents, and 9 in vitro metabolites in the rat hepatic S9 incubation system of the petroleum ether-soluble fraction were tentatively identified. All metabolites were found from Angelicae Sinensis Radix for the first time. Among them, 13 (three ferulic acid-related constituents, six senkyunolide D-related constituents, and four senkyunolide F-related constituents) were identified as new metabolites (new compounds). This study is the first to qualitatively characterize the chemical constituents of the potent anticoagulative extract of Angelicae Sinensis Radix and to explore its metabolism. The result is a notable improvement in the discovery of Angelicae Sinensis Radix metabolites, and it provides the chemical basis for the effective forms and pharmacodynamic substances (prototypes, metabolites, or both) of the anticoagulant activity of Angelicae Sinensis Radix. PMID- 26829521 TI - Patient Satisfaction With Electronic Health Record Use by Primary Care Nurse Practitioners. AB - The purpose of this research study was to determine if satisfaction and communication between the patient and the nurse practitioner are affected by allowing patients to view their electronic health records during the history portion of the primary care office visit compared with patients who do not view their records. A cross-sectional, experimental design was utilized for this study. The intervention group was shown several components of the electronic health record during the history portion of the nurse practitioner assessment. This group's scores on a patient satisfaction survey were compared with those of the control group, who were not shown the electronic health record. The study findings suggest that the introduction of the electronic health record does not affect patients' satisfaction related to the office visit by the nurse practitioner. PMID- 26829522 TI - Development of the Computerized Model of Performance-Based Measurement System to Measure Nurses' Clinical Competence. AB - Critical thinking skills and clinical competence are for providing quality patient care. The purpose of this study is to develop the Computerized Model of Performance-Based Measurement system based on the Clinical Reasoning Model. The system can evaluate and identify learning needs for clinical competency and be used as a learning tool to increase clinical competency by using computers. The system includes 10 high-risk, high-volume clinical case scenarios coupled with questions testing clinical reasoning, interpersonal, and technical skills. Questions were sequenced to reflect patients' changing condition and arranged by following the process of collecting and managing information, diagnosing and differentiating urgency of problems, and solving problems. The content validity and known-groups validity was established. The Kuder-Richardson Formula 20 was 0.90 and test-retest reliability was supported (r = 0.78). Nursing educators can use the system to understand students' needs for achieving clinical competence, and therefore, educational plans can be made to better prepare students and facilitate their smooth transition to a future clinical environment. Clinical nurses can use the system to evaluate their performance-based abilities and weakness in clinical reasoning. Appropriate training programs can be designed and implemented to practically promote nurses' clinical competence and quality of patient care. PMID- 26829523 TI - Thickness of the Meniscal Lamellar Layer: Correlation with Indentation Stiffness and Comparison of Normal and Abnormally Thick Layers by Using Multiparametric Ultrashort Echo Time MR Imaging. AB - Purpose To determine the relationship between lamellar layer thickness on ultrashort echo time (UTE) magnetic resonance (MR) images and indentation stiffness of human menisci and to compare quantitative MR imaging values between two groups with normal and abnormally thick lamellar layers. Materials and Methods This was a HIPAA-compliant, institutional review board-approved study. Nine meniscal pieces were obtained from seven donors without gross meniscal pathologic results (mean age, 57.4 years +/- 14.5 [standard deviation]). UTE MR imaging and T2, UTE T2*, and UTE T1rho mapping were performed. The presence of abnormal lamellar layer thickening was determined and thicknesses were measured. Indentation testing was performed. Correlation between the thickness and indentation stiffness was assessed, and mean quantitative MR imaging values were compared between the groups. Results Thirteen normal lamellar layers had mean thickness of 232 MUm +/- 85 and indentation peak force of 1.37 g +/- 0.87. Four abnormally thick lamellar layers showed mean thickness of 353.14 MUm +/- 98.36 and peak force 0.72 g +/- 0.31. In most cases, normal thicknesses showed highly positive correlation with the indentation peak force (r = 0.493-0.912; P < .001 to .05). However, the thickness in two abnormal lamellar layers showed highly negative correlation (r = -0.90, P < .001; and r = -0.23, P = .042) and no significant correlation in the others. T2, UTE T2*, and UTE T1rho values in abnormally thick lamellar layers were increased compared with values in normal lamellar layers, although only the UTE T2* value showed significant difference (P = .010). Conclusion Variation of lamellar layer thickness in normal human menisci was evident on two-dimensional UTE images. In normal lamellar layers, thickness is highly and positively correlated with surface indentation stiffness. UTE T2* values may be used to differentiate between normal and abnormally thickened lamellar layers. ((c)) RSNA, 2016. PMID- 26829524 TI - White Matter Injuries in Mild Traumatic Brain Injury and Posttraumatic Migraines: Diffusion Entropy Analysis. AB - Purpose To determine the performance of Shannon entropy (SE) as a diagnostic tool in patients with mild traumatic brain injury (mTBI) with posttraumatic migraines (PTMs) and those without PTMs on the basis of analysis of fractional anisotropy (FA) maps. Materials and Methods The institutional review board approved this retrospective study, with waiver of informed consent. FA maps were obtained and neurocognitive testing was performed in 74 patients with mTBI (57 with PTM, 17 without PTM). FA maps were obtained in 22 healthy control subjects and in 20 control patients with migraine headaches. Mean FA and SE were extracted from total brain FA histograms and were compared between patients with mTBI and control subjects and between patients with and those without PTM. Mean FA and SE were correlated with clinical variables and were used to determine the areas under the receiver operating characteristic curve (AUCs) and likelihood ratios for mTBI and development of PTM. Results Patients with mTBI had significantly lower SE (P < .001) and trended toward lower mean FA (P = .07) compared with control subjects. SE inversely correlated with time to recovery (TTR) (r = 0.272, P = .02). Patients with mTBI with PTM had significantly lower SE (P < .001) but not mean FA (P = .15) than did other patients with mTBI. SE provided better discrimination between patients with mTBI and control subjects than mean FA (AUC = 0.92; P = .01), as well as better discrimination between patients with mTBI with PTM and those without PTM (AUC = 0.85; P < .001). SE of less than 0.751 resulted in a 16.1 increased likelihood of having experienced mTBI and a 3.2 increased likelihood of developing PTM. Conclusion SE more accurately reveals mTBI than mean FA, more accurately reveals those patients with mTBI who develop PTM, and inversely correlates with TTR. ((c)) RSNA, 2016. PMID- 26829525 TI - Long-Time Plasma Membrane Imaging Based on a Two-Step Synergistic Cell Surface Modification Strategy. AB - Long-time stable plasma membrane imaging is difficult due to the fast cellular internalization of fluorescent dyes and the quick detachment of the dyes from the membrane. In this study, we developed a two-step synergistic cell surface modification and labeling strategy to realize long-time plasma membrane imaging. Initially, a multisite plasma membrane anchoring reagent, glycol chitosan-10% PEG2000 cholesterol-10% biotin (abbreviated as "GC-Chol-Biotin"), was incubated with cells to modify the plasma membranes with biotin groups with the assistance of the membrane anchoring ability of cholesterol moieties. Fluorescein isothiocyanate (FITC)-conjugated avidin was then introduced to achieve the fluorescence-labeled plasma membranes based on the supramolecular recognition between biotin and avidin. This strategy achieved stable plasma membrane imaging for up to 8 h without substantial internalization of the dyes, and avoided the quick fluorescence loss caused by the detachment of dyes from plasma membranes. We have also demonstrated that the imaging performance of our staining strategy far surpassed that of current commercial plasma membrane imaging reagents such as DiD and CellMask. Furthermore, the photodynamic damage of plasma membranes caused by a photosensitizer, Chlorin e6 (Ce6), was tracked in real time for 5 h during continuous laser irradiation. Plasma membrane behaviors including cell shrinkage, membrane blebbing, and plasma membrane vesiculation could be dynamically recorded. Therefore, the imaging strategy developed in this work may provide a novel platform to investigate plasma membrane behaviors over a relatively long time period. PMID- 26829526 TI - Nomenclature for factors of the HLA system, update December 2015. PMID- 26829527 TI - Nomenclature for factors of the HLA system, update November 2015. PMID- 26829528 TI - Nomenclature for factors of the HLA system, update October 2015. PMID- 26829529 TI - Extracellular polymeric substances, microbial activity and microbial community of biofilm and suspended sludge at different divalent cadmium concentrations. AB - The differences between biofilm and suspended sludge (S-sludge) in extracellular polymeric substances (EPS), microbial activity, and microbial community in an anoxic-aerobic sequencing batch biofilm reactor (SBBR) at different concentrations of divalent cadmium (Cd(II)) were investigated. As the increase of Cd(II) concentration from 0 to 50mgL(-1), the specific ammonium oxidation rate (SAOR), specific nitrite oxidation rate (SNOR), and specific nitrate reduction rate (SNRR) of biofilm decreased from 4.85, 5.22 and 45mgNg(-1) VSSh(-1) to 1.54, 2.38 and 26mgNg(-1)VSSh(-1), respectively, and the SAOR, SNOR and SNRR of S sludge decreased from 4.80, 5.02 and 34mgNg(-1)VSSh(-1) to 1.46, 2.20 and 17mgNg( 1)VSSh(-1), respectively. Biofilm had higher protein (PN) content in EPS than S sludge. Contrast to S-sludge, biofilm could provide Nitrobacter vulgaris, beta proteobacterium INBAF015, and Pseudoxanthomonas mexicana with the favorable conditions of growth and reproduction. PMID- 26829530 TI - Kinetics of co-pyrolysis of sawdust, coal and tar. AB - Two coals, sawdust and coal tar were selected to prepare briquettes. Thermogravimetric analyses at three heating rates (i.e. 10, 20 and 30 degrees C/min) and up to 1000 degrees C were carried out with the briquette components. Four blends were prepared and the experimental decomposition profiles were compared with the calculated data taking into account the amount of each component in the blend. No interaction was found when comparing the experimental and calculated decomposition profiles of the blends. Isoconversional models OFW (Ozawa-Flynn-Wall) and KAS (Kissinger-Akahira-Sunose) were used to obtain the activation energies of the blend components. The activation energies obtained were introduced in the Coats-Redfern (CR) model to derive the pre-exponential factors. The thermal decomposition profiles calculated using the kinetic parameters were in good agreement with the experimental results in the case of the briquette components, but worse results were obtained in the case of the blends due to their greater complexity. PMID- 26829531 TI - Molecular Lifting, Twisting, and Curling during Metal-Assisted Polycyclic Hydrocarbon Dehydrogenation. AB - The atomistic understanding of the dissociation mechanisms for large molecules adsorbed on surfaces is still a challenge in heterogeneous catalysis. This is especially true for polycyclic aromatic hydrocarbons, which represent an important class of organic compounds used to produce novel graphene-based architectures. Here, we show that coronene molecules adsorbed on Ir(111) undergo major conformational changes during dissociation. They first tilt upward with respect to the surface, still keeping their planar configuration, and subsequently experience a rotation, which changes the molecular axis orientation. Upon lifting, the internal C-C strain is initially relieved; as the dehydrogenation proceeds, the molecules experience a progressive increase in the average interatomic distance and gradually settle to form dome-shaped nanographene flakes. Our results provide important insight into the complex mechanism of molecular breakup, which could have implications in the synthesis of new carbon-based nanostructured materials. PMID- 26829532 TI - Fostering prevention and care delivery services capability on HIV pandemic and Ebola outbreak symbiosis in Africa. AB - Human immunodeficiency virus (HIV) and the re-emerging Ebola virus disease (EVD) are closely intertwined and remain a persistent public health threat and global challenge. Their origin and rapid transmission and spread have similar boundaries and share overlapping impact characteristics, including related symptoms and other interactions. The controversies and global threat of these viruses require rapid response policy and evidence-based implementation findings. The constraints and dual burden inflicted by Ebola and HIV infections are highly characterized by similar socio-demographics, socio-economic and political factors. EVD has similar effects and burdens to HIV infection. This study seeks to understand EVD in the context of HIV epidemic despite the challenges in developing an effective vaccine against HIV and EVD. Our findings show that early understanding, prevention and treatment of these diseases a global health threat mainly in Africa is important and valuable. The lessons learned so far from HIV and Ebola epidemics are crucial in health programming and execution of rapid response interventions and continued vigilance against EVD before it become another worldwide health menace. Therefore, the current regional West Africa EVD requires strengthening healthcare systems and building preparedness and response capacity. Importantly, appropriate community participation, health education and resilience coupled with deployment of effective novel diagnostic approaches in early warning and surveillance of threats and emerging diseases. Therefore, there is an urgent need to develop novel key strategies are crucial in curbing the constant viral resurgence, persistence transmission dynamics and spread, as well in accelerating Ebola vaccines regimen (immunization) development and national implementation plans in achieving sustained control, and eventual elimination. PMID- 26829533 TI - Influenza in Brazil: surveillance pathways. AB - Influenza is a viral disease of global concern that has demanded the attention of health authorities. Since 1947, as a preventive measure, the World Health Organization monitors viral circulation to define the annual vaccine through a worldwide network of laboratories. This article presents the structuring of influenza surveillance in Brazil and highlights virological surveillance and the role of diagnostic laboratories as well as the expansion of actions to improve detection and expedite responses. The model set corresponds to sentinel surveillance complemented by the universal notification of severe acute respiratory syndrome investigating outbreaks, deaths, and unusual events and monitoring hospitalization and mortality in an expanded surveillance. In this review, we address aspects of influenza surveillance in animals, the need for interagency integration, and the sharing of information in many surveillance systems. PMID- 26829534 TI - Concomitant outbreaks of yellow fever and hepatitis E virus in Darfur States, Sudan, 2012. AB - INTRODUCTION: Yellow fever (YF) is a vector-borne disease transmitted to humans by infected Aedes mosquitoes, while hepatitis E virus (HEV) is a waterborne disease that is transmitted through the fecal-oral route. Both diseases have very close clinical presentation, namely fever, jaundice, malaise, and dark urine; they differ in severity and outcome. METHODOLOGY: In this cross-sectional, laboratory-based study, an attempt was made to measure the correlation of concomitant YF and HEV infection in Darfur States during the previous YF outbreak in 2012. RESULTS: Results found concomitant outbreaks of YF and HEV at the same time with very weak statistical correlation between the two infections during the outbreak period, with Cramer's V correlation 0.05 and insignificant p value of 0.86. CONCLUSIONS: This correlation indicates that clinicians and care providers in tropical areas have to deal with clinical case definitions used for disease surveillance very carefully since prevalence of HEV infection is relatively common and this increases the possibility of misclassification and missing YF cases, particularly initial index cases, in a season or outbreak. PMID- 26829535 TI - Clinico-epidemiological profile of fever of unknown origin in an Egyptian setting: A hospital-based study (2009-2010). AB - INTRODUCTION: Fever of unknown origin (FUO) is one of the most challenging diagnostic dilemmas in the field of infectious diseases and tropical medicine. Clinicians should use the frequency distribution of disorders causing FUO to guide their diagnostic approach in patients with prolonged, unexplained fevers meeting the definition of FUO. METHODOLOGY: The present study was undertaken to examine the etiologies, clinico-epidemiologic profile, and prognosis of classical FUO in patients reporting to the Alexandria Fever Hospital in Egypt. Records of 979 patients admitted to the fever hospital (from January 2009 to January 2010) and diagnosed as having FUO were examined carefully. FUO was defined as three outpatient visits or three days in the hospital without elucidation of cause of fever. RESULTS: A total of 979 cases (57.0% males and 43.0% females), with ages ranging from 0.2 to 90 years, were investigated. The mean duration of fever before hospitalization was 31 +/- 10 days. The etiology of FUO was delineated in 97% of cases, and only 3% remained undiagnosed. Diagnoses were grouped into five major categories. Infectious causes of FUO were strongly associated with better outcome (73.7% improved). Smoking, contact with animals or birds, drug addiction, and HIV seropositivity were important risk factors associated with infections. CONCLUSIONS: Infections are the most common cause of FUO, followed by collagen vascular diseases, in our region. A three-step diagnostic work-up approach is recommended to be applied in Egypt in order to improve the quality of medical service provided to FUO patients. PMID- 26829536 TI - Extended-spectrum beta-lactamases, transferable quinolone resistance, and virulotyping in extra-intestinal E. coli in Uruguay. AB - INTRODUCTION: To characterize extended-spectrum beta-lactamases (ESBLs) and plasmid-mediated quinolone resistance (PMQR) genes in Escherichia coli isolates obtained from extra-intestinal samples in three Uruguayan hospitals. METHODOLOGY: Fifty-five ESBL-producing E. coli isolates were studied. Virulence genes, ESBLs, and PMQR genes were detected by polymerase chain reaction. ESBL-producing isolates were compared by pulsed-field gel electrophoresis. Multi-locus sequence typing was also performed on 13 selected isolates. RESULTS: Thirty-seven isolates harbored blaCTX-M-15 (67.3%), eight blaCTX-M-2 (14.6%), five blaCTX-M-14 (9.1%), three carried both blaCTX-M-2 and blaCTX-M-14, one blaCTX-M-9, and one blaCTX-M 8. Among the CTX-M-15 producers, 92% belonged to sequence types ST131 and ST405, and carried aac(6')Ib-cr as well. Isolates harboring blaCTX-M-2, blaCTX-M-14, blaCTX-M-9, or blaCTX-M-8 were found to be genetically unrelated. CONCLUSIONS: The successful dissemination of CTX-M-15-producing E.coli isolates seems to be linked to the spreading of high-risk clones and horizontal gene transfer. A trade off between carrying more antibiotic resistance and less virulence-related genes could partially account for the evolutionary advantages featured by successful clones. PMID- 26829537 TI - A duplex real-time PCR for the detection of Streptococcus pneumoniae and Neisseria meningitidis in cerebrospinal fluid. AB - INTRODUCTION: Acute bacterial meningitis is one of the most severe infectious diseases. Rapid, accurate, and inexpensive diagnosis of bacterial meningitis is crucial for patient management. This study describes a duplex real-time (RT) PCR assay for detection of Neisseria meningitidis and Streptococcus pneumoniae in the cerebrospinal fluid (CSF) for meningitis diagnosis using SYBR Green-based RT-PCR method coupled with melting curve analysis. METHODOLOGY: We used SYBR Green-based RT-PCR method coupled with melting curve analysis to detect S. pneumoniae and N. meningitidis in CSF samples. The sensitivity, specificity, and limit of detection were determined. The gold standard for routine tests of CSF analysis is direct examination, culture, and/or latex agglutination. The assay was evaluated on 132 CSF samples to measure clinical sensitivity. RESULTS: A duplex RT-PCR assay for N. meningitidis and S. pneumoniae detection in CSF was evaluated. Two peaks at different melting temperatures (87.5 degrees C and 85.5 degrees C) for N. meningitidis and S. pneumoniae, respectively, were obtained. The sensitivity of RT-PCR was 100% (95% confidence limits [CI] = 82.4-100) for N. meningitidis and 100% (95% CI = 85.1-100) for S. pneumoniae. Specificity was the same (100%) for the bacteria (95% CI = 88.6-100). The percentage of cases accurately diagnosed with meningitis caused by N. meningitidis and S. pneumoniae increased to 50.7% and 28.6%, respectively, when RT-PCR was added to the standard microbiologic methods. CONCLUSIONS: Duplex RT-PCR and melting curve analysis with SYBR Green is an inexpensive, sensitive, and specific method to rapidly diagnose bacterial meningitis. Accurate identification of the bacterial causative agents will improve patient management and epidemiological investigations. PMID- 26829538 TI - A multi-laboratory comparison of two molecular methods for the detection of toxigenic Clostridium difficile. AB - INTRODUCTION: Diarrheal disease due to toxigenic Clostridium difficile (CD) accounts for an increased number of hospitalizations and deaths each year. Published guidelines recommend reflex testing of CD antigen-positive samples to molecular testing or testing samples directly by a molecular assay. This multicenter study was designed to compare the accuracy of two different molecular methods targeting different CD genes: Xpert C. difficile Epi RUO RT-PCR assay (XPCR) which targets toxin B (Cepheid, Sunnyvale, CA) and a laboratory-developed PCR (LDPCR) which targets mutations in the tcdC regulatory gene. METHODOLOGY: Two molecular methods for toxigenic CD detection, the Xpert C. difficile Epi RUO RT PCR assay (XPCR) [Cepheid, Sunnyvale, CA] and a laboratory-developed PCR assay (LDPCR) were compared to a consensus gold standard (CGS) or toxigenic culture (TC) as the reference method. A subset of specimens was subjected to additional molecular characterization of toxigenic CD. RESULTS: Both molecular methods were >90% sensitive for CD detection. Discordant results were noted when molecular test results were compared to non-molecular methods. Supplemental molecular characterization illustrated inherent difficulties in comparisons using different molecular methods for CD. CONCLUSION: Laboratories may consider using multiple CD detection methods or combinations of methods, including molecular detection for rapid and accurate diagnosis of CD, as driven by best practices for the respective healthcare environment. Laboratories must be aware of intrinsic differences when comparing performance characteristics of different molecular assays. PMID- 26829539 TI - Characterization and horizontal transfer of class 1 integrons in Escherichia coli isolates from cooked meat products. AB - INTRODUCTION: Escherichia coli is a commensal bacterium in humans, animals, and the environment that is one of the microorganisms commonly resistant to antimicrobials. Cooked meat products, which are popular in China, are easily contaminated by E. coli during processing and storage. METHODOLOGY: In this study, a total of 75 E. coli isolates from cooked meat products in Henan province, China, were assayed for the presence of and horizontal transfer of class 1 integrons. RESULTS: Class 1 integrons were detected in 11 (14.7%) of these isolates, and contained four groups of resistance gene cassettes, including dfrA17-aadA5, dfrA1-aadA1, dfrA12-orfF-aadA2, and an uncommon array of aacA4 catB8-aadA1. The transfer frequency of selected integron-positve donors ranged from 10(-6) to 10(-4) transconjugants per recipient cell, and the integron containing DNA from the donors could be transferred to E. coli J53Azr with the transformation frequency of 10(-7) to 10(-5). CONCLUSIONS: Class 1 integrons could be transferred to recipient E. coli J53 by conjugation and natural transformation. These findings suggest the role of commensal E. coli isolates from cooked meats as an important reservoir for integrons and the possible transfer of antimicrobial resistance genes to humans via the food chain. PMID- 26829540 TI - Molecular analysis of the adaptive response in Salmonella Typhimurium after starvation in salty conditions. AB - INTRODUCTION: The pathogenic bacterium Salmonella enterica serovar Typhimurium elicits a variety of genetic programs to adapt to stress conditions encountered within hostile environments such as host phagocytes and preserved food. METHODOLOGY: In this work, differential display (DD) methodology was used to investigate the effect of one month starvation in a salty microcosm (0.5 M NaCl) on transcript profiling in a Salmonella Typhimurium LT2 strain. cDNA fragments resulting from differentially expressed mRNA were eluted from the gel, re amplified, cloned, and then sequenced. RESULTS: A total of 21 differentially expressed bands were detected by DD reverse transcription-polymerase chain reaction (RT-PCR). However, only 12 of them were successfully identified as upregulated genes in stressed cells. Based on the sequencing data and BLAST analysis, these genes were sopA, ssaD, yhhK, gmK, cspC, uspA, ompR, phoP, stcC, fimA, acrA,and yehZ. As a confirmation of the differential expression, RT-PCR was carried out using a set of specific primers. Remarkably, the expression levels of these genes were significantly increased in starved bacteria compared to standard laboratory conditions. CONCLUSIONS: Our results indicate that the starvation of Salmonella Typhimurium over one month in a salty microcosm changes the expression of stress proteins, response regulator in a two-component system, outer membrane proteins, effector proteins translocated by Salmonella pathogenicity island SPI1 and SPI2 type III secretion systems (TTSS), several metabolic enzymes, efflux pumps, and transport proteins. This suggests that the expression of the identified genes is important for the response of this pathogen to starvation in salt. PMID- 26829541 TI - Efficient attractants and simple odor-baited sticky trap for surveillance of Anopheles arabiensis Patton mosquito in Ethiopia. AB - INTRODUCTION: Many efforts have been made to ease the burden of malaria through vector control, among whichis the development of odor-baited traps and evaluation of efficient attractants that could replace host odor. However, most traps and evaluated attractants are expensive, which poor communities cannot afford. This study was conductedwith the aim to devise asimple and affordable odor-baited trap and to investigate effective but affordable attractants for trapping Anopheles arabiensis. METHODOLOGY: First, an odor-baited sticky trap was developed; next, an experimental study with randomized design was conducted to evaluate the efficacy of selected attractants for trapping Anopheles arabiensis using the designed trap from June to August 2014. Laboratory strain Anopheles arabiensis were obtainedfrom the Adama Malaria Research and Training Center Insectary. Wild Anopheline mosquito larvae were collected from a temporary breeding site, reared in Asendabo Vector Biology Laboratory, and tested. RESULTS: A simple odor-baited sticky trap was designed. Selected attractants were tested for attracting efficiency using the designed trap. Among the evaluated attractants, cow urine, which was kept for four days, attracted significantly more wild population and laboratory strains of the Anopheles arabiensisthan a worn sock alone and the combination of cow urine and a worn sock. CONCLUSIONS: Although further comparison studies with other standard traps are needed, the designed trap in conjunction with efficient attractant is shown to be effective for mosquito surveillance. Of the tested attractants, cow urine was anefficient attractant both for the wild population and the laboratory strain of Anohpeles arabiensis. PMID- 26829542 TI - Comparing immunological and molecular tests with conventional methods in diagnosis of acute invasive fungal rhinosinusitis. AB - INTRODUCTION: This study compared immunological and molecular testswith conventional methods in the diagnosis of acute invasive fungal rhinosinusitis. METHODOLOGY: All tissue samples from maxillary sinuses were cultured and stained using periodic acid-Schiff. Two blood samples were cultured by bedside inoculation into BACTEC medium. Diagnostic tests were used: enzyme-linked immunosorbent assay for detection of galactomannan and mannan in serum samples, real-time PCR assays for Aspergillus spp. and Candida spp., and nested PCR for the Mucoraceae family. RESULTS: Among 31 immunocompromised patients, based on host factors, clinical, radiological and mycological findings, 18 patients were diagnosed with documented infection. By direct smear examination, 9 patients (50%) had positive results for Mucoraceae family, but only 5 samples showed growth in the culture (55.5%). Nested PCR results for species in this family were negative in all serum samples from patients. In addition, 9 patients had positive direct microscopic findings, of which 7 specimens produced positive growth for Aspergillus flavus (77.7%). The galactomannan test was positive in 6/9 (66.6%), and Aspergillus PCR were positive in 6 patients (66.6%). The isolated agent was C. albicans in one patient. The mannan antigen test to detect Candida was negative. None of the blood cultures was positive for fungal infection. CONCLUSIONS: The efficient method to diagnose fungal rhinosinusitis was direct microscopic examination of tissue samples. Immunological and molecular methods, which are available for some important fungi, can help clinicians with the diagnosis and management of infections in patients in critical condition when tissue sampling is not available. PMID- 26829543 TI - Extensively drug-resistant Acinetobacter baumannii isolated in a university hospital: Role of inter-hospital transmission. AB - INTRODUCTION: Acinetobacter baumannii causes severe infections that primarily affect intensive care unit (ICU) patients. It has a high prevalence of multidrug resistance, including carbapenems, and a high potential for intra-hospital and inter-hospital transmission. The aim of this study was to determine the origin of extensively drug-resistant (XDR) A. baumannii isolates in our hospital during 2009. METHODOLOGY: This was an observational retrospective study. Isolates of A. baumannii were obtained from patients hospitalized during 2009. XDR isolates were defined using criteria published by Magiorakos et al.. The isolates were classified as community acquired, hospital acquired, and inter-hospital transmission. RESULTS: A total of 48 isolates of A. baumannii were isolated during 2009, corresponding to 34 patients. Of these, 18 (53%) were susceptible, 6 (18%) were multidrug resistant (MDR), and 10 (29%) were XDR. Of the 10 XDR isolates, 9 were isolated from patients transferred from other hospitals. The median time of hospitalization in origin hospitals was 17 days, while the median time of hospitalization in the study hospital, previous to isolation of A. baumannii, was 1 day. A total of 6 out of 10 patients had a positive culture taken on the day of admission. None of the patients shared a clinical ward or time during hospitalization. Genotypic characterization demonstrated the existence of two clones (A and B) which were geographically associated with patients transferred from two different regions of the country. CONCLUSIONS: During 2009, all XDR A. baumannii isolates were recovered from patients coming from other hospitals, indicative of inter-hospital transmission. PMID- 26829544 TI - Necrotizing fasciitis due to Streptococcus mitis caused by accidental human bite. AB - Human bite wounds are more prone to infection than animal bites, which may cause necrotizing soft tissue infections such as myositis, fasciitis. Both aerobic and anaerobic microorganisms may be responsible, including Streptococcus spp., Staphylococcus aureus, Peptostreptococcus spp. Necrotizing fasciitis is characterized by serious tissue destruction and systemic toxicity with high morbidity and mortality. We report a patient with Streptococcus mitis associated necrotizing fasciitis on the upper extremity resulting from an accidental human bite, which caused nearly fatal infection. Prophylactic antibiotic treatment should be given after a human bite to prevent infection. If the infection signs and symptoms develop, rapid diagnosis, appropriate antibiotic and surgical therapy should be administered immediately. Streptococcus mitis is a viridans streptococcus, usually known as a relatively benign oral streptococcus. To our knowledge, this is the first necrotizing fasciitis case due to Streptococcus mitis after human bite. PMID- 26829545 TI - Hemophagocytic lymphohistiocytosis and visceral leishmaniasis in children: case report and systematic review of literature. AB - Hemophagocytic lymphohistiocytosis is a potentially fatal disorder resulting from excessive activation and non-malignant proliferation of T lymphocytes and macrophages. Neoplasms, autoimmune disorders and systemic infections can cause secondary hemophagocytic syndrome. The association of hemophagocytic syndrome and visceral leishmaniasis is rarely found in childhood. We report a case of an infant affected by hemophagocytic lymphohistiocytosis secondary to visceral leishamniasis and describe all cases of hemophagocytic syndrome associated with visceral leishamniasis in childhood reported in literature, focusing on clinical manifestation, diagnosis and treatment. PMID- 26829546 TI - Comparative in-vitro activity of ceftaroline against Staphylococcus aureus isolates from India. PMID- 26829547 TI - Cobalt-Based Layered Metal-Organic Framework as an Ultrahigh Capacity Supercapacitor Electrode Material. AB - Metal-organic frameworks (MOFs) have recently received increasing interest due to their potential application in the energy storage and conversion field. Herein, cobalt-based layered MOF ({[Co(Hmt)(tfbdc)(H2O)2].(H2O)2}n, Co-LMOF; Hmt = hexamethylenetetramine; H2tfbdc = 2,3,5,6-tetrafluoroterephthalic acid) has been evaluated as an electrode material for supercapacitors. The Co-LMOF electrode exhibits a high specific capacitance and excellent cycling stability. Its maximum specific capacitance is 2474 F g(-1) at a current density of 1 A g(-1), and the specific capacitance retention is about 94.3% after 2000 cycles. The excellent electrochemical property may be ascribed to the intrinsic nature of Co-LMOF, enough space available for the storage and diffusion of the electrolyte, and the particles of nanoscale size. PMID- 26829548 TI - Solvent-Directed Assembly of a Pyridinium-Tailored Methyl Oleanolate Amphiphile: Stepwise Growth of Microrods and Nanofibers. AB - Although a few architectures have been fabricated by the self-assembly of natural triterpenoids, the precise control of shape and size is rarely studied. Herein, a methyl oleanolate-bearing amphiphile, 1-[2-(methyl oleanolate)-2 oxoethyl]pyridinium bromide (MOP), has been designed and its assembly behavior was investigated. It was found that the morphologies of MOP assemblies ranged from nanoparticles to rigid microrods and flexible nanofibers in chloroform/p xylene and methanol/water, respectively. During the assembly process, the systematical variational solvophobic/solvophilic effect resulted in the formation of spherical nanoparticles with opposite dipoles and converse bilayer structures. Moreover, such opposite molecular orientations lead to the inversion of supramolecular chirality and distinct mechanical properties. The driving forces and packing patterns of MOP in each solvent system were clearly demonstrated by the combination of NMR, UV-vis, Fourier transform infrared spectroscopy (FTIR), X ray diffraction (XRD), theoretical computation, and contact angle experiments, which revealed the roles of triterpenoids and pyridinium cations in the assembly process. This work provides a facile strategy to control the supramolecular structures in triterpenoid-based assemblies by adjusting the solvent polarity and composition. PMID- 26829549 TI - Depleted uranium induces sex- and tissue-specific methylation patterns in adult zebrafish. AB - We examined the effects of chronic exposure to different concentrations (2 and 20 MUg L(-)(1)) of environmentally relevant waterborne depleted uranium (DU) on the DNA methylation patterns both at HpaII restriction sites (5'-CCGG-3') and across the whole genome in the zebrafish brain, gonads, and eyes. We first identified sex-dependent differences in the methylation level of HpaII sites after exposure. In males, these effects were present as early as 7 days after exposure to 20 MUg L(-)(1) DU, and were even more pronounced in the brain, gonads, and eyes after 24 days. However, in females, hypomethylation was only observed in the gonads after exposure to 20 MUg L(-)(1) DU for 24 days. Sex-specific effects of DU were also apparent at the whole-genome level, because in males, exposure to 20 MUg L(-)(1) DU for 24 days resulted in cytosine hypermethylation in the brain and eyes and hypomethylation in the gonads. In contrast, in females, hypermethylation was observed in the brain after exposure to both concentrations of DU for 7 days. Based on our current knowledge of uranium toxicity, several hypotheses are proposed to explain these findings, including the involvement of oxidative stress, alteration of demethylation enzymes and the calcium signaling pathway. This study reports, for the first time, the sex- and tissue-specific epigenetic changes that occur in a nonhuman organism after exposure to environmentally relevant concentrations of uranium, which could induce transgenerational epigenetic effects. PMID- 26829551 TI - Molecular Characterization of the Recently Emerged Poultry Pathogen Ornithobacterium rhinotracheale by Multilocus Sequence Typing. AB - Ornithobacterium rhinotracheale (ORT) is an economically important bacterial pathogen of turkeys and chickens worldwide. Since its first detection, a variety of typing methods have been used to gain basic knowledge about the bacterial population structure, an issue that still needs to be addressed. Serological characterization revealed at least 18 different serotypes (A-R) with ORT of serotype A to be predominate among poultry. This study aimed to establish a multilocus sequence typing (MLST) scheme for ORT that could easily be used by other laboratories and allows for worldwide comparison of sequence data. For this purpose, 87 ORT strains from different poultry hosts, geographical origins, years of isolation and serotypes were included in the analysis to identify correlations. Fourteen different sequence types (ST) were found. The most common ST1 was identified in 40 ORT strains from turkeys and chickens on 4 continents and in 3 different European countries. Together with ST9, both STs represented over three quarters (77%) of ORT strains used in the MLST analysis and included strains of frequently cross-reacting ORT serotypes A, E and I. Nine STs were only represented by one ORT strain and might indicate possible avian host, disease or serotype-specific relationships. In contrast, discrepancies between serotype and phylogenetic relatedness were clearly demonstrated by ORT strains that belonged to identical serotypes but differed in their ST. The overall identified low genetic diversity among strains isolated from turkeys and chickens independent of host and geographical origins suggests that ORT has only recently been introduced into domestic poultry and dispersed worldwide. PMID- 26829550 TI - The Chlamydia trachomatis Protease CPAF Contains a Cryptic PDZ-Like Domain with Similarity to Human Cell Polarity and Tight Junction PDZ-Containing Proteins. AB - The need for more effective anti-chlamydial therapeutics has sparked research efforts geared toward further understanding chlamydial pathogenesis mechanisms. Recent studies have implicated the secreted chlamydial serine protease, chlamydial protease-like activity factor (CPAF) as potentially important for chlamydial pathogenesis. By mechanisms that remain to be elucidated, CPAF is directed to a discrete group of substrates, which are subsequently cleaved or degraded. While inspecting the previously solved CPAF crystal structure, we discovered that CPAF contains a cryptic N-terminal PSD95 Dlg ZO-1 (PDZ) domain spanning residues 106-212 (CPAF106-212). This PDZ domain is unique in that it bears minimal sequence similarity to canonical PDZ-forming sequences and displays little sequence and structural similarity to known chlamydial PDZ domains. We show that the CPAF106-212 sequence is homologous to PDZ domains of human tight junction proteins. PMID- 26829552 TI - Recombinant Mouse beta-Defensin 3 Protects against Coxsackievirus B3-Induced Myocarditis in Mice. AB - OBJECTIVES: To investigate the protective effect of recombinant mouse beta defensin 3 (rMBD3) against coxsackievirus B3 (CVB3)-induced myocarditis in mice. METHODS: CVB3-infected HeLa cells were treated with rMBD3, and the titer of CVB3 and the proliferative activities of the cells were determined. CBV3-infected BALB/c mice were divided into five groups: rMBD3 high (5 mg/kg/day, q.d.), rMBD3 low (2.5 mg/kg/day, q.d.), ribavirin (10 mg/kg/day, q.d.), normal control, and myocarditis control. On days 5 and 12 after treatment, 3 mice from each group were sacrificed and serum lactate dehydrogenase, creatine kinase-MB isozyme, and tumor necrosis factor-alpha levels were determined. The heart index and the inflammation of myocardial tissue were also assessed. On day 5, the CVB3 50% tissue culture infective dose (TCID50) values of heart tissues were measured. RESULTS: rMBD3 inhibited the replication of CVB3 and protected HeLa cells from infection. rMBD3 reduced the CVB3 titer markedly and inhibited the pathological reaction of cardiac myocytes to viral myocarditis. Treatment with rMBD3 improved the cell survival rate and reduced the cardiac index. CONCLUSION: rMBD3 was demonstrated to possess anti-CVB3 activity in vivo and in vitro. PMID- 26829553 TI - Genome-Wide Analysis of the Lysine Biosynthesis Pathway Network during Maize Seed Development. AB - Lysine is one of the most limiting essential amino acids for humans and livestock. The nutritional value of maize (Zea mays L.) is reduced by its poor lysine content. To better understand the lysine biosynthesis pathway in maize seed, we conducted a genome-wide analysis of the genes involved in lysine biosynthesis. We identified lysine biosynthesis pathway genes (LBPGs) and investigated whether a diaminopimelate pathway variant exists in maize. We analyzed two genes encoding the key enzyme dihydrodipicolinate synthase, and determined that they contribute differently to lysine synthesis during maize seed development. A coexpression network of LBPGs was constructed using RNA-sequencing data from 21 developmental stages of B73 maize seed. We found a large set of genes encoding ribosomal proteins, elongation factors and zein proteins that were coexpressed with LBPGs. The coexpressed genes were enriched in cellular metabolism terms and protein related terms. A phylogenetic analysis of the LBPGs from different plant species revealed different relationships. Additionally, six transcription factor (TF) families containing 13 TFs were identified as the Hub TFs of the LBPGs modules. Several expression quantitative trait loci of LBPGs were also identified. Our results should help to elucidate the lysine biosynthesis pathway network in maize seed. PMID- 26829554 TI - Induction of IL-10 and TGFbeta from CD4+CD25+FoxP3+ T Cells Correlates with Parasite Load in Indian Kala-azar Patients Infected with Leishmania donovani. AB - BACKGROUND: Visceral leishmaniasis (VL) is distinguished by a complex interplay of immune response and parasite multiplication inside host cells. However, the direct association between different immunological correlates and parasite numbers remains largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We examined the plasma levels of different disease promoting/protective as well as Th17 cytokines and found IL-10, TGFbeta and IL-17 to be significantly correlated with parasite load in VL patients (r = 0.52, 0.53 and 0.51 for IL-10, TGFbeta and IL-17, respectively). We then extended our investigation to a more antigen-specific response and found leishmanial antigen stimulated levels of both IL-10 and TGFbeta to be significantly associated with parasite load (r = 0.71 and 0.72 for IL-10 and TGFbeta respectively). In addition to cytokines we also looked for different cellular subtypes that could contribute to cytokine secretion and parasite persistence. Our observations manifested an association between different Treg cell markers and disease progression as absolute numbers of CD4+CD25+ (r = 0.55), CD4+CD25hi (r = 0.61) as well as percentages of CD4+CD25+FoxP3+ T cells (r = 0.68) all correlated with parasite load. Encouraged by these results, we investigated a link between these immunological components and interestingly found both CD4+CD25+ and CD4+CD25+FoxP3+ Treg cells to secrete significantly (p<0.05) higher amounts of not only IL-10 but also TGFbeta in comparison to corresponding CD25- T cells. CONCLUSIONS/SIGNIFICANCE: Our findings shed some light on source(s) of TGFbeta and suggest an association between these disease promoting cytokines and Treg cells with parasite load during active disease. Moreover, the direct evidence of CD4+CD25+FoxP3+ Treg cells as a source of IL-10 and TGFbeta during active VL could open new avenues for immunotherapy towards cure of this potentially fatal disease. PMID- 26829555 TI - Leptin and Pro-Inflammatory Stimuli Synergistically Upregulate MMP-1 and MMP-3 Secretion in Human Gingival Fibroblasts. AB - INTRODUCTION: Gingival fibroblast-mediated extracellular matrix remodelling is implicated in the pathogenesis of periodontitis, yet the stimuli that regulate this response are not fully understood. The immunoregulatory adipokine leptin is detectable in the gingiva, human gingival fibroblasts express functional leptin receptor mRNA and leptin is known to regulate extracellular matrix remodelling responses in cardiac fibroblasts. We therefore hypothesised that leptin would enhance matrix metalloproteinase secretion in human gingival fibroblasts. METHODS AND RESULTS: We used in vitro cell culture to investigate leptin signalling and the effect of leptin on mRNA and protein expression in human gingival fibroblasts. We confirmed human gingival fibroblasts expressed cell surface leptin receptor, found leptin increased matrix metalloproteinase-1, -3, -8 and 14 expression in human gingival fibroblasts compared to unstimulated cells, and observed that leptin stimulation activated MAPK, STAT1/3 and Akt signalling in human gingival fibroblasts. Furthermore, leptin synergised with IL-1 or the TLR2 agonist pam2CSK4 to markedly enhance matrix metalloproteinase-1 and -3 production by human gingival fibroblasts. Signalling pathway inhibition demonstrated ERK was required for leptin-stimulated matrix metalloproteinase-1 expression in human gingival fibroblasts; whilst ERK, JNK, p38 and STAT3 were required for leptin+IL 1- and leptin+pam2CSK4-induced matrix metalloproteinase-1 expression. A genome wide expression array and gene ontology analysis confirmed genes differentially expressed in leptin+IL-1-stimulated human gingival fibroblasts (compared to unstimulated cells) were enriched for extracellular matrix organisation and disassembly, and revealed that matrix metalloproteinase-8 and -12 were also synergistically upregulated by leptin+IL-1 in human gingival fibroblasts. CONCLUSIONS: We conclude that leptin selectively enhances the expression and secretion of certain matrix metalloproteinases in human gingival fibroblasts, and suggest that gingival fibroblasts may have an ECM-degrading phenotype during conditions of hyperleptinaemia (e.g., obesity, type 2 diabetes mellitus, exogenous leptin therapy). PMID- 26829556 TI - Methods of assessing associated reactions of the upper limb in stroke and traumatic brain injury: A systematic review. AB - OBJECTIVE: To determine the assessment methods for upper limb (UL) associated reactions (ARs) in people with acquired brain injury (ABI). METHODS: A systematic search of 10 databases was performed for Stage 1 to identify methods that quantify ARs of the hemiplegic UL. Stage 2 searched four databases to examine the clinimetric properties and clinical utility of these methods. Two independent reviewers identified relevant articles, extracted data, assessed study methodological quality and rated the clinimetric properties and clinical utility. RESULTS: Eighteen articles were included. The methods used to evaluate ARs were surface electromyography (11), goniometry (5), dynamometry (5), electrogoniometry (1), subjective clinician (2) and patient rating forms (2). Electromyography, electrogoniometry and dynamometry implemented stationary, seated positions using maximal voluntary contractions of the less impaired UL as the provocative task. Standard goniometry most frequently tested ARs dynamically, using a mobility task to provoke the AR. There was limited clinimetric data available. Only half of the assessment methods were deemed clinically feasible. The most common methods were laboratory-based. CONCLUSION: There were a limited number of methods used to assess ARs in people with ABI and the measurement properties of these outcomes were largely unreported. No gold standard was identified. PMID- 26829558 TI - Vitamin D3 and calcidiol are not equipotent. AB - Despite the discussion on the optimal threshold of 25-hydroxyvitamin D serum level continues, there is now consensus on the fact that post-menopausal and elderly populations have inadequate Vitamin D serum levels worldwide. The adjustment of these levels is necessary to improve both bone and general health, as it is to optimize bone response to antiresortive treatments. It is recommended, as endorsed by international clinical guides, to use Vitamin D3, the physiological form of Vitamin D, in a dose range between 600-2000IU. It should be administered on a daily basis or on its weekly or monthly equivalents. In Spain, the use of calcidiol (25(OH)D3) at the same dose than Vitamin D3 is the most extended prescription, notwithstanding the available evidence stating that they are not equipotent. This may lead to over-dosage. In order to provide evidence on this circumstance, a convenience study was performed. Four groups of ten post menopausal osteoporotic women each (average age 67), deficient in Vitamin D ((25(OH)D 37.5+/-10 nmol/L)) were enrolled. Each group followed a different treatment regimen: (G1) vitamin D3 20MUg/day [800IU/day]; (G2) 25 (OH)D3 20MUg/day; (G3) 25(OH)D3 266MUg/week and (G4) 25(OH)D3 0.266mg every two weeks. 25(OH)D levels were measured for each group at 0, 6 and 12 months, with the following results: G1 (40.5+/-4.7;80.0+/-2; 86.2+/-23.7), G2 (37,2+/-4.2; 161+/ 21.7;188.0+/-24.0), G3 (38+/-3.7;213.5+/-80.0; 233.0+/-81.2), G4 (39.5+/ 4;164.5+/-41,7;210.5+/-22.2). These data reveal that both metabolites are not equipotent. Calcidiol is faster and 3-6 times more potent to obtain serum levels of 25(OH)D in the medium to long term. This circumstance must be assessed and included in the therapeutic prescription guides for Osteoporosis, since it should be of concern when planning and prescribing treatments to normalize serum levels of 25(OH)D3 and avoid potential adverse impacts. PMID- 26829559 TI - Corticosteroid-binding globulin (CBG) reactive centre loop antibodies and surface plasmon resonance interrogate the proposed heat dependent "flip-flop" mechanism of human CBG. AB - Corticosteroid-binding globulin (CBG) is the predominant carrier of cortisol in circulation and is a non-inhibitory member of the serpin superfamily of serine protease inhibitors. In the stressed or "S" conformation, CBG possesses an intact exposed reactive centre loop (RCL) that can be irreversibly cleaved by elastase released from activated human neutrophils whereupon it adopts a relaxed or "R" conformation. The latter conformation has decreased affinity for cortisol, allowing the release of the majority of cortisol at sites of inflammation. Recently there has been speculation that mild increments in heat such as found in pyrexia (39-40 degrees C) may also induce a reversible "flip-flop" of the RCL into the body of the protein structure, without cleavage, facilitating a reversible temperature-dependent release of cortisol. Here we raised a new monoclonal antibody to the RCL of human CBG and used this in concert with an existing RCL antibody and show by surface plasma resonance that, at temperatures up to 40 degrees C, the RCL of purified CBG and the RCL of CBG in intact plasma is accessible to these two antibodies. Together, the epitopes of these antibodies span 11 consecutive amino acids (STGVTLNLTSK) of the 18 residues of the RCL. This adequate antibody cover of the RCL sequence leads to the conclusion that the proposed temperature-dependent "flip-flop" of the RCL of CBG is doubtful. PMID- 26829557 TI - IFNs Modify the Proteome of Legionella-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid. AB - Macrophages can be niches for bacterial pathogens or antibacterial effector cells depending on the pathogen and signals from the immune system. Here we show that type I and II IFNs are master regulators of gene expression during Legionella pneumophila infection, and activators of an alveolar macrophage-intrinsic immune response that restricts bacterial growth during pneumonia. Quantitative mass spectrometry revealed that both IFNs substantially modify Legionella-containing vacuoles, and comparative analyses reveal distinct subsets of transcriptionally and spatially IFN-regulated proteins. Immune-responsive gene (IRG)1 is induced by IFNs in mitochondria that closely associate with Legionella-containing vacuoles, and mediates production of itaconic acid. This metabolite is bactericidal against intravacuolar L. pneumophila as well as extracellular multidrug-resistant Gram positive and -negative bacteria. Our study explores the overall role IFNs play in inducing substantial remodeling of bacterial vacuoles and in stimulating production of IRG1-derived itaconic acid which targets intravacuolar pathogens. IRG1 or its product itaconic acid might be therapeutically targetable to fight intracellular and drug-resistant bacteria. PMID- 26829560 TI - Editorial Comment. PMID- 26829561 TI - Reply by Authors. PMID- 26829563 TI - Re: Application of quantitative PCR assays for diagnosing Ikeda and other Theileria orientalis types to examine associations between severity of anaemia and parasitaemia in bovine anaemia outbreaks. PMID- 26829562 TI - Specific cellular accumulation of photofrin-II in EC cells promotes photodynamic treatment efficacy in esophageal cancer. AB - Photodynamic therapy (PDT), which uses a light-sensitive compound and laser irradiation, is a light-based oncological treatment modality. PDT offers an alternative, less invasive treatment for various malignant tumors, such as esophageal cancer (EC), through a photochemical reaction induced by photofrin-II or other oncotropic photosensitizers without severe complications. Previous studies has shown that cancerous tissues accumulated more photosensitizers than paired normal tissues, however, whether it is cellular or vascular mechanisms remains unknown. Herein, in vivo and in vitro examinations were performed to study the mechanisms by which photofrin-II effectively and specifically killed EC cells. In this study, EC tissue of patients treated with photofrin-II, human ESCC cellline SHEEC and parental normal cellline SHEE, primary culture cells of EC tissue were used. The concentration of photofrin-II in cells were evaluated by high-performance liquid chromatography (HPLC). The results exhibited that accumulation of photofrin-II in cancerous cells were significantly higher than that in non-cancerous cells (p<0.05) under certain dose and time period of incubation of photofrin-II. In summary, our study showed that, photofrin-II specifically accumulated in EC cells in vivo and in vitro after controlling for vascular factors, which provided strong evidence that maybe the cellular factor is the main mechanism by which photofrin-II-mediated PDT selectively caused EC cells death. PMID- 26829564 TI - Optical Coherence Tomography Angiography of Choroidal Neovascularization Associated with Tuberculous Serpiginous-like Choroiditis. AB - Choroidal neovascularization secondary to tuberculous serpiginous-like choroiditis (Tb-SLC) is uncommon and requires further invasive imaging, such as fluorescein and indocyanine green angiography. We evaluate the optical coherence tomography angiography (OCTA) findings in a patient with a Tb-SLC and present the use of this investigation as a non-invasive diagnostic and follow-up clinical tool in this disease. PMID- 26829566 TI - Fractionation of an ECM hydrogel into structural and soluble components reveals distinctive roles in regulating macrophage behavior. AB - Extracellular matrix (ECM) derived from mammalian tissues has been utilized to repair damaged or missing tissue and improve healing outcomes. More recently, processing of ECM into hydrogels has expanded the use of these materials to include platforms for 3-dimensional cell culture as well as injectable therapeutics that can be delivered by minimally invasive techniques and fill irregularly shaped cavities. At the cellular level, ECM hydrogels initiate a multifaceted host response that includes recruitment of endogenous stem/progenitor cells, regional angiogenesis, and modulation of the innate immune response. Unfortunately, little is known about the components of the hydrogel that drive these responses. We hypothesized that different components of ECM hydrogels could play distinctive roles in stem cell and macrophage behavior. Utilizing a well-characterized ECM hydrogel derived from urinary bladder matrix (UBM), we separated the soluble and structural components of UBM hydrogel and characterized their biological activity. Perivascular stem cells migrated toward and reduced their proliferation in response to both structural and soluble components of UBM hydrogel. Both components also altered macrophage behavior but with different fingerprints. Soluble components increased phagocytosis with an IL 1RA(high), TNFalpha(low), IL-1beta(low), uPA(low) secretion profile. Structural components decreased phagocytosis with a PGE2(high), PGF2alpha(high), TNFalpha(low), IL-1beta(low), uPA(low), MMP2(low), MMP9(low), secretion profile. The biologic activity of the soluble components was mediated by Notch and PI3K/Akt signaling, while the biologic activity of the structural components was mediated by integrins and MEK/ERK signaling. Collectively, these findings demonstrate that soluble and structural components of ECM hydrogels contribute to the host response but through different mechanisms. PMID- 26829565 TI - Effect of 3'UTR RET Variants on RET mRNA Secondary Structure and Disease Presentation in Medullary Thyroid Carcinoma. AB - BACKGROUND: The RET S836S variant has been associated with early onset and increased risk for metastatic disease in medullary thyroid carcinoma (MTC). However, the mechanism by which this variant modulates MTC pathogenesis is still open to discuss. Of interest, strong linkage disequilibrium (LD) between RET S836S and 3'UTR variants has been reported in Hirschsprung's disease patients. OBJECTIVE: To evaluate the frequency of the RET 3'UTR variants (rs76759170 and rs3026785) in MTC patients and to determine whether these variants are in LD with S836S polymorphism. METHODS: Our sample comprised 152 patients with sporadic MTC. The RET S836S and 3'UTR (rs76759170 and rs3026785) variants were genotyped using Custom TaqMan Genotyping Assays. Haplotypes were inferred using the phase 2.1 program. RET mRNA structure was assessed by Vienna Package. RESULTS: The mean age of MTC diagnosis was 48.5+/-15.5 years and 57.9% were women. The minor allele frequencies of RET polymorphisms were as follows: S836S, 5.6%; rs76759170, 5.6%; rs3026785, 6.2%. We observed a strong LD among S836S and 3'UTR variants (|D'| = 1, r2 = 1 and |D'| = -1, r2 = 0,967). Patients harboring the S836S/3'UTR variants presented a higher percentage of lymph node and distant metastasis (P = 0.013 and P<0.001, respectively). Accordingly, RNA folding analyses demonstrated different RNA secondary structure predictions for WT(TCCGT), S836S(TTCGT) or 3'UTR(GTCAC) haplotypes. The S836S/3'UTR haplotype presented a greater number of double helices sections and lower levels of minimal free energy when compared to the wild-type haplotype, suggesting that these variants provides the most thermodynamically stable mRNA structure, which may have functional consequences on the rate of mRNA degradation. CONCLUSION: The RET S836S polymorphism is in LD with 3'UTR variants. In silico analysis indicate that the 3'UTR variants may affect the secondary structure of RET mRNA, suggesting that these variants might play a role in posttranscriptional control of the RET transcripts. PMID- 26829567 TI - Ultra-high gain diffusion-driven organic transistor. AB - Emerging large-area technologies based on organic transistors are enabling the fabrication of low-cost flexible circuits, smart sensors and biomedical devices. High-gain transistors are essential for the development of large-scale circuit integration, high-sensitivity sensors and signal amplification in sensing systems. Unfortunately, organic field-effect transistors show limited gain, usually of the order of tens, because of the large contact resistance and channel length modulation. Here we show a new organic field-effect transistor architecture with a gain larger than 700. This is the highest gain ever reported for organic field-effect transistors. In the proposed organic field-effect transistor, the charge injection and extraction at the metal-semiconductor contacts are driven by the charge diffusion. The ideal conditions of ohmic contacts with negligible contact resistance and flat current saturation are demonstrated. The approach is general and can be extended to any thin-film technology opening unprecedented opportunities for the development of high performance flexible electronics. PMID- 26829568 TI - Modification with polysialic acid-PEG copolymer as a new method for improving the therapeutic efficacy of proteins. AB - A new protein derivatization method was developed with a block copolymer to reduce the immunogenicity of therapeutic proteins. The block copolymer consisted of polyethylene glycol (PEG) and polysialic acid (PSA), a nonimmunogenic and biodegradable biopolymer. Uricase was used as a model protein. Molecular weight analysis results indicated that the uricase-PEG-PSA conjugate was linked with 2.5 copolymers for each uricase unit. The residual enzyme activity of the uricase with modification by the PEG-PSA copolymer was 72.4%. The tolerance and stability to heat, acid, alkaline, and trypsin treatments significantly improved compared with the native uricase. The immunogenicity of uricase modified with PEG-PSA copolymer was remarkably reduced. The transmission electron microscopy results of the uricase-PEG-PSA conjugate showed a spherical hydrated shell with a larger particle size. These findings proved that the PSA-PEG-protein conjugate is a formulation that can potentially be used to deliver the protein and peptide-based drugs. PMID- 26829569 TI - Stevens-Johnson syndrome: The role of an ophthalmologist. AB - Stevens-Johnson syndrome (SJS) is an acute blistering disease of the skin and mucous membranes. Acute SJS leads to the acute inflammation of the ocular surface and chronic conjunctivitis. If not properly treated, it causes chronic cicatricial conjunctivitis and cicatricial lid margin abnormalities. Persistent inflammation and ulceration of the ocular surface with cicatricial complications of the lids leads to chronic ocular sequelae, ocular surface damage, and corneal scarring. The destruction of the glands that secrete the tear film leads to a severe form of dry eye that makes the management of chronic SJS difficult. The option that is routinely used for corneal visual rehabilitation, keratoplasty, is best avoided in such cases. We describe the management strategies that are most effective during the acute and chronic stages of SJS. Although treatments for acute SJS involve immunosuppressive and immunomodulatory therapies, amniotic membrane transplantation is also useful. The options for visual rehabilitation in patients with chronic SJS are undergoing radical change. We describe the existing literature regarding the management of SJS and highlight recent advances in the management of this disorder. PMID- 26829570 TI - Direct Observation of Defect Range and Evolution in Ion-Irradiated Single Crystalline Ni and Ni Binary Alloys. AB - Energetic ions have been widely used to evaluate the irradiation tolerance of structural materials for nuclear power applications and to modify material properties. It is important to understand the defect production, annihilation and migration mechanisms during and after collision cascades. In this study, single crystalline pure nickel metal and single-phase concentrated solid solution alloys of 50%Ni50%Co (NiCo) and 50%Ni50%Fe (NiFe) without apparent preexisting defect sinks were employed to study defect dynamics under ion irradiation. Both cross sectional transmission electron microscopy characterization (TEM) and Rutherford backscattering spectrometry channeling (RBS-C) spectra show that the range of radiation-induced defect clusters far exceed the theoretically predicted depth in all materials after high-dose irradiation. Defects in nickel migrate faster than in NiCo and NiFe. Both vacancy-type stacking fault tetrahedra (SFT) and interstitial loops coexist in the same region, which is consistent with molecular dynamics simulations. Kinetic activation relaxation technique (k-ART) simulations for nickel showed that small vacancy clusters, such as di-vacancies and tri vacancies, created by collision cascades are highly mobile, even at room temperature. The slower migration of defects in the alloy along with more localized energy dissipation of the displacement cascade may lead to enhanced radiation tolerance. PMID- 26829571 TI - Factors that bring meaning to mementos created by elders. AB - OBJECTIVES: Reminiscing activity groups are commonly seen in various elder care settings This study addresses the impact of reminiscence activity groups, specifically a program where group members create their own mementos, on healthy Jewish elders' sense of satisfaction and meaning. In particular, this research focused on the specific factors involved in creating the mementos themselves. METHOD: In this mixed methods study, occupational therapy graduate students synthesized relevant aspects of commonly used activity analysis forms into a matrix to analyze the activities. From a pool of 30 activities, students chose seven representing many factors and levels of complexity. With a matrix composed of a Likert scale and open-ended questions, students and Jewish elders explored the elders' perceptions of factors significantly related to their experiences when creating the seven mementos. RESULTS: Memento-making was most satisfying when elders were replicated in some way, such as with hand casting. Least satisfying activities were those that could lead to talents being appraised, such as painted self-portraits. Unanticipated factors such as social participation and educating others appeared to be as important as making the mementos themselves. CONCLUSION: While the research questions were partially answered, factors such as meaning and creativity were difficult constructs to measure because they lacked clear definitions. However, this preliminary exploration supports the concept that the use of an activity analysis matrix can enable activities directors and occupational therapists to systematically ascertain which factors positively impact well-being and social participation to meet the unique needs of aging client populations. PMID- 26829572 TI - The place of Homo floresiensis in human evolution. AB - Two main evolutionary scenarios have been proposed to explain the presence of the small-bodied and small-brained Homo floresiensis species on the remote Indonesian island of Flores in the Late Pleistocene. According to these two scenarios, H. floresiensis was a dwarfed descendent of H. erectus or a late-surviving remnant of a older lineage, perhaps descended from H. habilis. Each scenario has interesting and important implications for hominin biogeography, body size evolution, brain evolution and morphological convergences. Careful evaluation reveals that only a small number of characters support each of these scenarios uniquely. H. floresiensis exhibits a cranial shape and many cranial characters that appear to be shared derived traits with H. erectus, but postcranial traits are more primitive and resemble those of early Homo or even australopiths. Mandibular and dental traits show a mix of derived and primitive features. Unfortunately, many traits cannot be used to assess these two hypotheses because their distribution in H. erectus, early Homo (e.g., H. habilis), or both is unknown. H. erectus ancestry implies evolutionary convergence on a postcranial configuration similar to australopiths and early Homo, which could be explained by a return to more climbing behaviors. Body size reduction as well as brain size reduction on a scale only rarely documented in mammals would also accompany the origin of H. floresiensis from a H. erectus ancestor. H. habilis ancestry implies parallel evolution of numerous cranial characters, as well as a few dentognathic traits. A pre-H. erectus ancestry also suggests an early migration to Southeast Asia that is as yet undocumented in mainland Asia, but minimal body and brain size reduction. PMID- 26829573 TI - Make it clear: molds, transparent casts and lightning techniques for stereomicroscopic analysis of taphonomic modifications on bone surfaces. AB - This paper provides detailed description of a non-destructive, low-cost, and low time consuming technique for producing high-resolution casts for the observation of taphonomic modifications on bone surfaces. The aim of the whole process is to obtain molds that accurately replicate the original bone surface at both the macro- and microscopic levels. The high quality transparent epoxy casts produced are analyzed by light microscopy and used to produce detailed microphotographs of bone surfaces. After describing each step of the process, we present some examples of its application in the case of anthropic activity, carnivores, or other post-depositional modifications. PMID- 26829574 TI - Visuospatial integration and human evolution: the fossil evidence. AB - Visuospatial integration concerns the ability to coordinate the inner and outer environments, namely the central nervous system and the outer spatial elements, through the interface of the body. This integration is essential for every basic human activity, from locomotion and grasping to speech or tooling. Visuospatial integration is even more fundamental when dealing with theories on extended mind, embodiment, and material engagement. According to the hypotheses on extended cognition, the nervous system, the body and the external objects work as a single integrated unit, and what we call "mind" is the process resulting from such interaction. Because of the relevance of culture and material culture in humans, important changes in such processes were probably crucial for the evolution of Homo sapiens. Much information in this sense can be supplied by considering issues in neuroarchaeology and cognitive sciences. Nonetheless, fossils and their anatomy can also provide evidence according to changes involving physical and body aspects. In this article, we review three sources of morphological information concerning visuospatial management and fossils: evolutionary neuroanatomy, manipulative behaviors, and hand evolution. PMID- 26829575 TI - Multi-level human evolution: ecological patterns in hominin phylogeny. AB - Evolution is a process that occurs at many different levels, from genes to ecosystems. Genetic variations and ecological pressures are hence two sides of the same coin; but due both to fragmentary evidence and to the influence of a gene-centered and gradualistic approach to evolutionary phenomena, the field of paleoanthropology has been slow to take the role of macro-evolutionary patterns (i.e. ecological and biogeographical at large scale) seriously. However, several very recent findings in paleoanthropology stress both climate instability and ecological disturbance as key factors affecting the highly branching hominin phylogeny, from the earliest hominins to the appearance of cognitively modern humans. Allopatric speciation due to geographic displacement, turnover-pulses of species, adaptive radiation, mosaic evolution of traits in several coeval species, bursts of behavioral innovation, serial dispersals out of Africa, are just some of the macro-evolutionary patterns emerging from the field. The multilevel approach to evolution proposed by paleontologist Niles Eldredge is adopted here as interpretative tool, and has yielded a larger picture of human evolution that integrates different levels of evolutionary change, from local adaptations in limited ecological niches to dispersal phenotypes able to colonize an unprecedented range of ecosystems. Changes in global climate and Earth's surface most greatly affected human evolution. Precisely because it is cognitively hard for us to appreciate the long-term common destiny we share with the whole biosphere, it is particularly valuable to highlight the accumulating evidence that human evolution has been deeply affected by global ecological changes that transformed our African continent of origin. PMID- 26829576 TI - Prevalence of Gastrointestinal Parasites in Civets of Fragmented Rainforest Patches in Anamalai Hills, Western Ghats, India. AB - : Parasitism, driven by anthropogenic habitat modifications, is being increasingly recognized as a major threat to wildlife. Unfortunately, even baseline parasite data for most wildlife species are lacking in India, including the civets, which are particularly vulnerable due to their proximity to human habitations. Civet fecal samples were collected from 10 forest fragments that vary in size and disturbance level in Anamalai Hills, Western Ghats, India. These samples were screened for the presence of gastrointestinal parasites using fecal floatation and fecal sedimentation techniques. From a total of 180 civet fecal samples, 15 gastrointestinal parasite taxa were recovered, and these species are also known to infect domesticated animals. Additionally, small, disturbed forest fragments recorded higher mean gastrointestinal parasite taxa and greater prevalence when compared to large, undisturbed forest fragments, indicating a potential relationship between anthropogenic activities and gastrointestinal parasitism of civets in the Anamalai Hills. PMID- 26829577 TI - The effect of dietary methionine levels on fattening performance and selected blood and tissue parameters of turkeys. AB - A total of 490 eight-week-old female Hybrid Converter turkeys (body weight 4.11 +/- 0.03 kg) were divided into 5 groups with 7 replicates of 14 birds each. For 8 weeks, basal diets were supplemented with methionine (Met) at following levels (weeks 9-12/weeks 13-16 of age): Group 1 - 0.34/0.29%, Group 2 - 0.39/0.34%, Groups 3 and 4 - 0.45/0.38% and 0.51/0.41%, respectively, Group 5 - 0.58/0.47%. Only in the first feeding phase the body weight gain (BWG) was affected by Met levels with the significantly highest BWG in Group 3. No treatment effects were found for feed conversion ratio, carcass yield, carcass composition and meat colour. The blood superoxide dismutase activity was significantly highest in Groups 2 and 3. The concentrations of reduced glutathione in the liver were linearly increased (p = 0.018), whereas the ratio of reduced glutathione to oxidised glutathione was highest in Group 3 (quadratic contrast, p = 0.004). It can be concluded that turkeys from Group 3 (Met levels age depending 15% and 10% above recommendations by NRC) were characterised by a well-balanced physiological response. Attention should be paid to the immune response of birds to higher dietary Met levels: plasma IgA concentrations decreased, whereas IL-6 and TNF alpha levels increased in turkeys fed diets with the highest Met content. PMID- 26829578 TI - A droplet-based microfluidic immunosensor for high efficiency melamine analysis. AB - We report a droplet-based microfluidic immunosensor for the rapid and accurate detection of melamine, an organic base that has been implicated in widescale adulteration of food products such as milk. Our melamine assay is based on the competitive reaction between native melamine and a melamine-fluorescein isothiocyanate (FITC) conjugate against an anti-hapten antibody. The adoption of fluorescence polarization, allows the quantification of melamine in a more direct and rapid manner than established heterogeneous methods based on liquid chromatography, mass spectrometry, and enzyme-linked immunosorbent assay (ELISA). The detection protocol provides a limit of detection of 300 ppb, which is below the maximum allowable melamine levels (2.5 ppm) defined by the U.S. Food and Drug Administration and the European Commission to a significant extent. PMID- 26829579 TI - Detection of KRAS mutations using double-stranded toehold-exchange probes. AB - Detection of KRAS mutations in cancer tissues is immensely valuable for the identification of personalized genotype-based therapy. Here, we employed a double stranded toehold-exchange probe, which is labeled with fluorescent molecules (FAM) and quenchers (Dabcyl), to detect KRAS mutations in cancer tissues. This probe was able to differentiate the intended mutation in a sample containing as little as 5% mutant alleles in a background of wild-type DNA. This probe also performed robustly at a wide range of conditions, for examples, from 4 degrees C to 37 degrees C, from 200 mM Na(+) to 1M Na(+), and from 200 mM K(+) to 500 mM K(+). Furthermore, we validated the practicality of this probe in a clinical setting using 8 pairs of cancer tissue samples and their NT (corresponding adjacent nontumorous tissue) samples. All the results generated from the probe detection agreed with those from direct sequencing. Combining features of extreme high specificity and robustness, this probe is a valuable tool for reliable diagnosis of cancer-related mutations. PMID- 26829580 TI - Stereoselective Synthesis of Substituted Oxocene Cores by Lewis Acid Promoted Cyclization. AB - Substituted oxocene derivatives have been synthesized by Lewis acid catalyzed reactions of epsilon-hydroxyalkene and substituted aromatic aldehydes. The Cu(OTf)2-bis-phosphine catalyzed reaction typically provides substituted dihydropyran derivatives through an olefin migration followed by a Prins cyclization. The corresponding reaction catalyzed by TMSOTf or BF3.OEt2 provided eight-membered cyclic ethers (oxocenes), selectively. This methodology provides convenient access to a variety of 2,4,8-trisubstituted oxocenes in good yields and excellent diastereoselectivities. PMID- 26829581 TI - A systematic review of fractional exhaled nitric oxide in the routine management of childhood asthma. AB - BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker of eosinophilic inflammation which may be used to guide the management of asthma in childhood. OBJECTIVES: To synthesise the available evidence on the efficacy of FeNO-guided management of childhood asthma. METHODS: Databases including MEDLINE and the Cochrane Library were searched, and randomised controlled trials (RCTs) comparing FeNO-guided management with any other monitoring strategy were included. Study quality was assessed using the Cochrane risk of bias tool for RCTs, and a number of outcomes were examined, including: exacerbations, medication use, quality of life, adverse events, and other markers of asthma control. Meta-analyses were planned if multiple studies with suitable heterogeneity were available. However, due to wide variations in study characteristics, meta-analysis was not possible. RESULTS: Seven RCTs were identified. There was some evidence that FeNO-guided monitoring results in improved asthma control during the first year of management, although few results attained statistical significance. The impact on severe exacerbations was unclear. Similarly, the impact on use of anti-asthmatic drugs was unclear, and appears to depend on the step up/down protocols, and the clinical characteristics of patients. CONCLUSIONS: The potential benefit of FeNO monitoring is equivocal. Trends toward reduced exacerbation and increased medication use were seen, but typically failed to reach statistical significance. There are a number of issues that complicate data interpretation, including differences in the likely severity of included cohorts and variations in treatment algorithms. Further work is needed to systematically explore the impact of these parameters. PMID- 26829582 TI - Oncocytic carcinoma of the major salivary glands: A population-based study of 278 cases. AB - BACKGROUND: Oncocytic carcinomas of the major salivary glands are extremely rare, with <100 cases reported. METHODS: A retrospective review of the National Cancer Database was performed from 1998 to 2012. RESULTS: We found 278 cases of major salivary oncocytic carcinoma. Most patients were men (61.9%), white (84.8%), with parotid disease (88.5%). Median age was 67 years (range, 16-90 years). Regional and distant metastases were found in 36.4% and 4.7% of cases. Overall survival at 5 and 10-years was 64% and 39%, respectively. Distant metastasis (hazard ratio [HR] = 13.87; 95% confidence interval [CI] = 2.98-64.52; p = .0010) and regional metastasis (HR = 3.01; 95% CI = 1.20-7.55; p = .019) are significant negative predictors, whereas positive margins approached significance (HR = 3.01; 95% CI = 1.20-7.55; p = .074). CONCLUSION: Oncocytic carcinoma has a poor long-term prognosis and lymph node metastases are common. Distant and regional metastases are significant predictors of decreased survival. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1981-E1986, 2016. PMID- 26829583 TI - Environmental Applications of Interfacial Materials with Special Wettability. AB - Interfacial materials with special wettability have become a burgeoning research area in materials science in the past decade. The unique surface properties of materials and interfaces generated by biomimetic approaches can be leveraged to develop effective solutions to challenging environmental problems. This critical review presents the concept, mechanisms, and fabrication techniques of interfacial materials with special wettability, and assesses the environmental applications of these materials for oil-water separation, membrane-based water purification and desalination, biofouling control, high performance vapor condensation, and atmospheric water collection. We also highlight the most promising properties of interfacial materials with special wettability that enable innovative environmental applications and discuss the practical challenges for large-scale implementation of these novel materials. PMID- 26829584 TI - Research highlights: impacts of microplastics on plankton. AB - Each year, millions of metric tons of the plastic produced for food packaging, personal care products, fishing gear, and other human activities end up in lakes, rivers, and the ocean. The breakdown of these primary plastics in the environment results in microplastics, small fragments of plastic typically less than 1-5 mm in size. These synthetic particles have been detected in all of the world's oceans and also in many freshwater systems, accumulating in sediment, on shorelines, suspended in surface waters, and being ingested by plankton, fish, birds, and marine mammals. While the occurrence of plastics in surface waters has been surveyed in a number of studies, the impacts of microplastics on marine organisms are still being elucidated. This highlight features three recent publications that explore the interactions of microplastics with planktonic organisms to clarify the effects of these pollutants on some of the ocean's smallest and most important inhabitants. PMID- 26829585 TI - Tibiotalocalcaneal Fusion for Severe Deformity and Bone Loss. AB - Tibiotalocalcaneal fusion is an effective salvage procedure for combined end stage ankle and subtalar arthrosis and for the management of severe planar deformities of the ankle and hindfoot. Although the procedure results in a rigid ankle and hindfoot, it is often the only means of providing patients with a stable and painless foot and ankle for ambulation. Some patients who require the procedure have substantial bone loss that can be managed with a variety of autograft and allograft options. Options for tibiotalocalcaneal fixation include both internal and external devices, the selection of which depends on the underlying pathology, amount of bone loss, and type of bone graft selected. Relatively high complication rates associated with tibiotalocalcaneal fusion have been reported, with complications ranging from superficial infection to ultimate amputation; however, proper patient selection and careful graft and fixation planning can minimize the postoperative complications of the procedure. PMID- 26829586 TI - New perspective of the bHLH-MYB complex in jasmonate-regulated plant fertility in arabidopsis. AB - Jasmonates (JAs) are a class of plant hormones, essential in plant development and defense. JA induces the interaction of the JA receptor Coronatine Insensitive 1 with jasmonate ZIM-domain (JAZ) proteins, and promotes subsequent JAZs degradation, leading to the release of downstream factors and activation of diverse plant development and defense processes. We recently revealed that the IIIe bHLH transcription factors MYC2, MYC3, MYC4 and MYC5 interact with the MYB transcription factors MYB21 and MYB24 to form the bHLH-MYB complex, and JAZs repress the bHLH-MYB complex to regulate JA-mediated stamen development. Here, we further discuss the different properties of the components of the bHLH-MYB complex in expression pattern and stamen regulation. PMID- 26829587 TI - Cytogenetic Diversity and the Evolutionary Dynamics of rDNA Genes and Telomeric Sequences in the Ancistrus Genus (Loricariidae: Ancistrini). AB - The Ancistrus genus differs from other Ancistrini due to its wide karyotypic diversity, varied diploid numbers, differences in sex chromosomes, and large number of species, as well as its tendency to form small populations with low vagility. This study investigated the role of 5S and 18S rDNA and telomeric repetitive sequences in the evolution of the karyotypic macrostructure of seven species of the genus Ancistrus from the Central Amazon. The results indicate a strong correlation between the location of ribosomal sites and fragile sites in the genome, particularly of 5S rDNA sequences, which are associated, in some species, with telomeric sequences at the sites of chromosomal healing. Moreover, the occurrence of two lineages was observed with regard to the synteny of ribosomal genes. The species of the genus Ancistrus showed high chromosomal lability associated with breakpoints, which was characterized by the presence of repetitive DNA sequences and this process is suggested to be an evolutionary model for the rapid fixation of structural rearrangements. PMID- 26829588 TI - Implementation of Complex Biological Logic Circuits Using Spatially Distributed Multicellular Consortia. AB - Engineered synthetic biological devices have been designed to perform a variety of functions from sensing molecules and bioremediation to energy production and biomedicine. Notwithstanding, a major limitation of in vivo circuit implementation is the constraint associated to the use of standard methodologies for circuit design. Thus, future success of these devices depends on obtaining circuits with scalable complexity and reusable parts. Here we show how to build complex computational devices using multicellular consortia and space as key computational elements. This spatial modular design grants scalability since its general architecture is independent of the circuit's complexity, minimizes wiring requirements and allows component reusability with minimal genetic engineering. The potential use of this approach is demonstrated by implementation of complex logical functions with up to six inputs, thus demonstrating the scalability and flexibility of this method. The potential implications of our results are outlined. PMID- 26829590 TI - A common mechanism underlies changes of mind about decisions and confidence. AB - Decisions are accompanied by a degree of confidence that a selected option is correct. A sequential sampling framework explains the speed and accuracy of decisions and extends naturally to the confidence that the decision rendered is likely to be correct. However, discrepancies between confidence and accuracy suggest that confidence might be supported by mechanisms dissociated from the decision process. Here we show that this discrepancy can arise naturally because of simple processing delays. When participants were asked to report choice and confidence simultaneously, their confidence, reaction time and a perceptual decision about motion were explained by bounded evidence accumulation. However, we also observed revisions of the initial choice and/or confidence. These changes of mind were explained by a continuation of the mechanism that led to the initial choice. Our findings extend the sequential sampling framework to vacillation about confidence and invites caution in interpreting dissociations between confidence and accuracy. PMID- 26829591 TI - A new view of transcriptome complexity and regulation through the lens of local splicing variations. AB - Alternative splicing (AS) can critically affect gene function and disease, yet mapping splicing variations remains a challenge. Here, we propose a new approach to define and quantify mRNA splicing in units of local splicing variations (LSVs). LSVs capture previously defined types of alternative splicing as well as more complex transcript variations. Building the first genome wide map of LSVs from twelve mouse tissues, we find complex LSVs constitute over 30% of tissue dependent transcript variations and affect specific protein families. We show the prevalence of complex LSVs is conserved in humans and identify hundreds of LSVs that are specific to brain subregions or altered in Alzheimer's patients. Amongst those are novel isoforms in the Camk2 family and a novel poison exon in Ptbp1, a key splice factor in neurogenesis. We anticipate the approach presented here will advance the ability to relate tissue-specific splice variation to genetic variation, phenotype, and disease. PMID- 26829592 TI - The Melanocortin Receptor Accessory Protein 2 promotes food intake through inhibition of the Prokineticin Receptor-1. AB - The Melanocortin Receptor Accessory Protein 2 (MRAP2) is an important regulator of energy homeostasis and its loss causes severe obesity in rodents. MRAP2 mediates its action in part through the potentiation of the MC4R, however, it is clear that MRAP2 is expressed in tissues that do not express MC4R, and that the deletion of MRAP2 does not recapitulate the phenotype of Mc4r KO mice. Consequently, we hypothesized that other GPCRs involved in the control of energy homeostasis are likely to be regulated by MRAP2. In this study we identified PKR1 as the first non-melanocortin GPCR to be regulated by MRAP2. We show that MRAP2 significantly and specifically inhibits PKR1 signaling. We also demonstrate that PKR1 and MRAP2 co-localize in neurons and that Mrap2 KO mice are hypersensitive to PKR1 stimulation. This study not only identifies new partners of MRAP2 but also a new pathway through which MRAP2 regulates energy homeostasis. PMID- 26829593 TI - Sonochemical enzyme-catalyzed regioselective acylation of flavonoid glycosides. AB - This work compares a highly efficient and alternative method of sonication assisted lipase catalyzed acylation of quercetin-3-O-glucoside and phloretin-2' glucoside, using Candida antarctica lipase B (Novozyme 435((r))), with a range of fatty acids. In this study, sonication-assisted irradiation coupled with stirring has been found to be more efficient and economical than conventional reaction conditions. Sonication-assisted acylation accelerated the reactions and reduced the time required by 4-5 folds. PMID- 26829594 TI - Enhanced Depth Imaging Optical Coherence Tomography in Uveitis: An Intravisit and Interobserver Reproducibility Study. AB - PURPOSE: To determine the intravisit and interobserver reproducibility of subfoveal choroidal thickness (SFCT) measurements in patients with noninfectious uveitis. DESIGN: Reliability analysis. METHODS: Two consecutive enhanced depth imaging optical coherence tomography (EDI-OCT) scans were obtained at a single clinic visit for 97 uveitic eyes from patients >=16 years of age with noninfectious anterior (n = 10), intermediate (n = 11), posterior (n = 26), and panuveitis (n = 13) at the National Eye Institute. SFCT was manually measured by 2 ophthalmologists using manufacturer's software. Intravisit and interobserver reproducibility of SFCT measurements were assessed by using the Bland-Altman method to determine the estimate of bias (mean difference in SFCT measurements), 95% limits of agreement, and coefficients of repeatability. The reproducibility of these measurements was also compared between groups by anatomic location and clinical activity. RESULTS: Of 97 eyes, 65 (67.0%) were clinically quiet, 18 (18.6%) were minimally active, and 14 (14.4%) were active at the time the scans were obtained. Manual SFCT measurements were reproducible within 32.4 +/- 3.8 MUm between sessions for the same observer and 51.4 +/- 8.5 MUm between observers for the same session. Coefficients of repeatability did not differ significantly by anatomic location or disease activity. CONCLUSIONS: Manual SFCT measurements obtained by EDI-OCT are reproducible in uveitis patients, with coefficients of repeatability that are nearly comparable to those published for normal eyes. This study provides guidance for using manual SFCT measurements in clinical practice, but further studies are still needed to determine their utility in clinical trials. PMID- 26829595 TI - Visual Outcomes and Accommodative Response of the Lumina Accommodative Intraocular Lens. AB - PURPOSE: To compare visual acuity, accommodation, and contrast sensitivity of the AkkoLens Lumina accommodative intraocular lens (AkkoLens Clinical b.v., Breda, The Netherlands) with a standard monofocal intraocular lens (IOL). DESIGN: Randomized clinical trial. METHODS: The study enrolled 86 eyes with cataract that all required cataract surgery and IOL implantation. The study group included 61 eyes that were implanted with the Lumina. The control group included 25 eyes that were implanted with an Acrysof SA60AT (Alcon, Fort Worth, TX, USA) monofocal IOL. The distance and near visual acuities, contrast sensitivity, and accommodation were measured over a 1-year follow-up period. Accommodation was measured subjectively, using defocus curves, and objectively, with an open-field autorefractor. RESULTS: Uncorrected (UDVA) and corrected (CDVA) distance visual acuities did not differ significantly between the groups (P >= .21) over the 12 months. However, the uncorrected near visual acuity (UNVA) was 0.07 +/- 0.08 logRAD for the Lumina group and 0.37 +/- 0.19 logRAD for the control group (P < .01) and the corrected distance near visual acuity (CDNVA) was 0.11 +/- 0.12 LogRAD for the Lumina group and 0.41 +/- 0.15 LogRAD for the control group (P < .01). Defocus curves showed a statistically significant difference between groups for defocus ranging from -4.50 to -0.50 diopters (D) (P < .01) with significantly higher visual acuities for the Lumina group. Subjective accommodation, as determined from defocus curves, was 3.05 +/- 1.06, 3.87 +/- 1.27, and 5.59 +/- 1.02 D for the Lumina group and 1.46 +/- 0.54, 2.00 +/- 0.52, and 3.67 +/- 0.75 D for the control group at visual acuities of 0.10, 0.20, and 0.4 logMAR for both groups, respectively. The objective accommodation, measured by an open-field autorefractor, was 0.63 +/- 0.41, 0.69 +/- 0.45, 0.91 +/- 0.51, and 1.27 +/- 0.76 D for the Lumina group and 0.10 +/- 0.15, 0.12 +/- 0.15, -0.06 +/- 0.09 and 0.07 +/- 0.10 D for the control group at accommodation stimuli of 2.0, 2.5, 3.0, and 4.0 D, respectively. Contrast sensitivity was the same for both groups (P >= .26). CONCLUSIONS: The Lumina accommodative IOL effectively restores the visual function, accommodation, and contrast sensitivity after cataract surgery with no influence on the postoperative contrast sensitivity. PMID- 26829596 TI - A Lack of Significant Effect of POR*28 Allelic Variant on Tacrolimus Exposure in Kidney Transplant Recipients. AB - BACKGROUND: POR*28 is a recently newly described allelic variant of the cytochrome P450 oxidoreductase (POR), which might be associated with an increased metabolic activity of P450 cytochromes (CYP) 3A5 and 3A4. Consequently, carriers of at least 1 allele of this polymorphism could require increased calcineurin inhibitors doses to reach the target residual concentrations (C0). The objective of this study was to test whether the allelic variant of POR, which is associated with an increased metabolic activity of CYP3A, impacts tacrolimus (Tac) pharmacokinetics. METHODS: We tested this hypothesis in a population of 229 kidney transplant recipients (KTR) from a large, multicenter, prospective and randomized study. We have analyzed the association between POR*28 genotype and the proportion of individuals reaching the target Tac residual concentration (Tac C0) 10 days after transplantation. We have also measured the association between POR*28 and the Tac C0, and adjusted Tac C0 (Tac C0/Tac dose) over time using generalized mixed linear models. RESULTS: Ten days after transplantation, there was no difference of frequencies of KTR within the target range of Tac C0 (C0 10 15 ng/mL) according to the POR*28 genotype (P = 0.8). The mean Tac C0 at day 10 in the POR*1/*1 group was 15.3 +/- 9.7 ng/mL compared with 15.7 +/- 7.8 ng/mL in the POR*1/*28 group and 14.2 +/- 6.8 ng/mL, in the POR*28/*28 group, P = 0.8. The adjusted Tac C0 was not associated with POR*28 genotype over time (random effects model, P = 0.9). When restricted to KTR expressing CYP3A5, POR*28 genotype did not impact the proportion of individuals within the Tac C0 target range neither the adjusted Tac C0 (random effects model, P = 0.1). CONCLUSIONS: POR*28 does not significantly influence Tac pharmacokinetic parameters in a large cohort of KTR. This study does not confirm recent findings indicating that POR*28 carriers require more Tac to reach target C0. PMID- 26829597 TI - Prediction of an Optimal Dose of Lamotrigine for Augmentation Therapy in Treatment-Resistant Depressive Disorder From Plasma Lamotrigine Concentration at Week 2. AB - BACKGROUND: The authors have previously shown that an early therapeutic response to lamotrigine augmentation therapy is dependent on its plasma concentration and that a plasma lamotrigine concentration of 12.7 MUmol/L may be a threshold for a good therapeutic response in treatment-resistant depressive disorder. The present study investigated whether or not an optimal dose of lamotrigine could be predicted from plasma lamotrigine concentration at week 2. METHODS: The subjects were 37 depressed patients who had already shown insufficient response to at least 3 psychotropics including antidepressants, mood stabilizers, and atypical antipsychotics. The diagnoses were major depressive disorder (n = 15), bipolar I disorder (n = 6), and bipolar II disorder (n = 16). They received augmentation therapy with lamotrigine for 8 weeks. The final doses of lamotrigine were 100 mg/d for 16 subjects who were not taking valproate and 75 mg/d for 21 subjects taking valproate, respectively. Blood sampling was performed at weeks 2 and 8. Plasma concentrations of lamotrigine were measured by high-performance liquid chromatography. RESULTS: There were significant linear relationships between the plasma lamotrigine concentrations at week 2 (x) and those at week 8 (y) for subjects who were not taking valproate (P < 0.01) and those taking valproate (P < 0.01). Regression equations were y = 2.032x + 2.549 for the former and y = 3.599x + 5.752 for the latter, respectively. Based on the equations, a nomogram to estimate an optimal dose of lamotrigine could be calculated. CONCLUSIONS: The present study suggests that an optimal dose of lamotrigine for augmentation therapy in treatment-resistant depressive disorder can be predicted from a plasma lamotrigine concentration at week 2. PMID- 26829598 TI - Evaluation of Limited Sampling Methods for Oral Busulfan Pharmacokinetic Monitoring in Adult Patients Undergoing Hematopoietic Stem Cell Transplantation. AB - BACKGROUND: Monitoring busulfan area under the plasma concentration-time curve (AUC) to establish the dose regimen for stem cell transplantation desirable to achieve efficacy while avoiding toxicity. OBJECTIVE: Our objective was to compare AUCs calculated by 18 limited sampling methods (LSMs) from 2 to 5 samples to reference AUCs determined from 10 samples in a retrospective study of 103 adult patients receiving oral busulfan. LSMs using 2 or 3 samples were ineffective. METHODS: Four LSMs using 4 or 5 blood samples that accurately characterized busulfan AUC were identified. The best 2 methods were obtained with sampling at 0.5, 1, 2, 4, and 6 hours and after 1, 1.5, 2, 4, and 6 hours postdose. For these LSMs, the incidence of 20% difference between AUCs from LSMs and reference AUCs was less than 1.3%. CONCLUSIONS: Effective and safe determination of AUC for oral busulfan can be made with strategies using only 4 or 5 concentration timepoints. PMID- 26829599 TI - Pharmacokinetic Analysis of Mycophenolate Mofetil and Enteric-Coated Mycophenolate Sodium in Calcineurin Inhibitor-Free Renal Transplant Recipients. AB - BACKGROUND: Considerable interest exists in identifying calcineurin inhibitor (CNI)-free and thus, less-toxic immunosuppressive regimens, with mycophenolic acid (MPA)-based treatments being a suitable approach. Because pharmacokinetic analyses of MPA treatments in stable CNI-free renal transplant recipients are lacking, the authors aimed at comparing the steady-state pharmacokinetic characteristics of MPA in patients on stable treatment with mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS) plus prednisone (<=5 mg/d). METHODS: In the prospective, nonrandomized, open-label study, patients with stable transplant function since >=6 months received their routine single dose of either MMF (n = 12) or EC-MPS (n = 11). The MPA plasma concentration was recorded over 12 hours. Parameters assessed were predose MPA concentration (C0), postdose minimum and maximum concentration (Cmin and Cmax), time to maximum concentration (Tmax), and area under the concentration-time curve (AUC) for the 12-hours of exposure (AUC0-12). RESULTS: Baseline characteristics were comparable between both the groups. Consistent with enteric coating, the mean Tmax was significantly longer after the intake of EC-MPS compared with MMF (2.2 versus 0.8 hours; P = 0.0002). The exposure measures Cmin, Cmax, and AUC0-12 were not significantly different despite the higher mean MPA equivalent dose in patients receiving MMF compared with those receiving EC-MPS (85% versus 64% of the recommended single dose, respectively). Exposures as reflected by the median AUC0-12 values were 50.7 and 58.7 mg.h.L with MMF and EC-MPS, respectively (P = 0.340). All patients achieved a target AUC of >30 mg.h.L, and 61% had an AUC of >50 mg.h.L. CONCLUSIONS: The study provides first results on the steady-state pharmacokinetics of the 2 MPA drugs in CNI-free immunosuppressant regimens. Pharmacokinetic parameters measured in this study under real-life conditions were comparable in patients receiving MMF or EC-MPS. PMID- 26829601 TI - Population pharmacokinetics of sirolimus in pediatric patients with neurofibromatosis type 1-Erratum. PMID- 26829600 TI - Accurately Achieving Target Busulfan Exposure in Children and Adolescents With Very Limited Sampling and the BestDose Software. AB - BACKGROUND: Busulfan dose adjustment is routinely guided by plasma concentration monitoring using 4-9 blood samples per dose adjustment, but a pharmacometric Bayesian approach could reduce this sample burden. METHODS: The authors developed a nonparametric population model with Pmetrics. They used it to simulate optimal initial busulfan dosages, and in a blinded manner, they compared dosage adjustments using the model in the BestDose software to dosage adjustments calculated by noncompartmental estimation of area under the time-concentration curve at a national reference laboratory in a cohort of patients not included in model building. RESULTS: Mean (range) age of the 53 model-building subjects was 7.8 years (0.2-19.0 years) and weight was 26.5 kg (5.6-78.0 kg), similar to nearly 120 validation subjects. There were 16.7 samples (6-26 samples) per subject to build the model. The BestDose cohort was also diverse: 10.2 years (0.25-18 years) and 46.4 kg (5.2-110.9 kg). Mean bias and imprecision of the 1 compartment model-predicted busulfan concentrations were 0.42% and 9.2%, and were similar in the validation cohorts. Initial dosages to achieve average concentrations of 600-900 ng/mL were 1.1 mg/kg (<=12 kg, 67% in the target range) and 1.0 mg/kg (>12 kg, 76% in the target range). Using all 9 concentrations after dose 1 in the Bayesian estimation of dose requirements, the mean (95% confidence interval) bias of BestDose calculations for the third dose was 0.2% (-2.4% to 2.9%, P = 0.85), compared with the standard noncompartmental method based on 9 concentrations. With 1 optimally timed concentration 15 minutes after the infusion (calculated with the authors' novel MMopt algorithm) bias was -9.2% ( 16.7% to -1.5%, P = 0.02). With 2 concentrations at 15 minutes and 4 hours bias was only 1.9% (-0.3% to 4.2%, P = 0.08). CONCLUSIONS: BestDose accurately calculates busulfan intravenous dosage requirements to achieve target plasma exposures in children up to 18 years of age and 110 kg using only 2 blood samples per adjustment compared with 6-9 samples for standard noncompartmental dose calculations. PMID- 26829602 TI - Aberrant expression of angiopoietin-like proteins 1 and 2 in cumulus cells is potentially associated with impaired oocyte developmental competence in polycystic ovary syndrome. AB - Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder associated with obesity, insulin resistance, hyperandrogenism, alterations in ovarian angiogenesis and impaired oocyte competence. Emerging evidence demonstrates that angiopoietin-like protein 1 (ANGPTL1) and angiopoietin-like protein 2 (ANGPTL2) have an important influence on angiogenesis, androgen biosynthesis, insulin resistance and adipocytes function. In this study, we set out to determine the potential relationship between ANGPTL1, ANGPTL2 and oocyte competence in PCOS through analyzing the expression levels and dynamic pattern of the two genes in cumulus cells (CCs) during different phases of nuclear maturation of PCOS patients and control groups undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer. We found that the relative abundance of ANGPTL1 and ANGPTL2 transcripts in CCs from patients with PCOS showed dynamic changes during oocyte maturation. Specifically, their expressions were increased significantly at the Metaphase II stage. In summary, the present novel evidence indicates that the expression patterns of ANGPTL1 and ANGPTL2 mRNAs are disordered during oocyte maturation in PCOS, which were potentially related to aberrant oocyte quality and developmental potency, at least in part, via pathological angiogenesis and metabolism. PMID- 26829603 TI - Pinning cluster synchronization in an array of coupled neural networks under event-based mechanism. AB - Cluster synchronization is a typical collective behavior in coupled dynamical systems, where the synchronization occurs within one group, while there is no synchronization among different groups. In this paper, under event-based mechanism, pinning cluster synchronization in an array of coupled neural networks is studied. A new event-triggered sampled-data transmission strategy, where only local and event-triggering states are utilized to update the broadcasting state of each agent, is proposed to realize cluster synchronization of the coupled neural networks. Furthermore, a self-triggered pinning cluster synchronization algorithm is proposed, and a set of iterative procedures is given to compute the event-triggered time instants. Hence, this will reduce the computational load significantly. Finally, an example is given to demonstrate the effectiveness of the theoretical results. PMID- 26829604 TI - Effects of self-coupling and asymmetric output on metastable dynamical transient firing patterns in arrays of neurons with bidirectional inhibitory coupling. AB - Metastable dynamical transient patterns in arrays of bidirectionally coupled neurons with self-coupling and asymmetric output were studied. First, an array of asymmetric sigmoidal neurons with symmetric inhibitory bidirectional coupling and self-coupling was considered and the bifurcations of its steady solutions were shown. Metastable dynamical transient spatially nonuniform states existed in the presence of a pair of spatially symmetric stable solutions as well as unstable spatially nonuniform solutions in a restricted range of the output gain of a neuron. The duration of the transients increased exponentially with the number of neurons up to the maximum number at which the spatially nonuniform steady solutions were stabilized. The range of the output gain for which they existed reduced as asymmetry in a sigmoidal output function of a neuron increased, while the existence range expanded as the strength of inhibitory self-coupling increased. Next, arrays of spiking neuron models with slow synaptic inhibitory bidirectional coupling and self-coupling were considered with computer simulation. In an array of Class 1 Hindmarsh-Rose type models, in which each neuron showed a graded firing rate, metastable dynamical transient firing patterns were observed in the presence of inhibitory self-coupling. This agreed with the condition for the existence of metastable dynamical transients in an array of sigmoidal neurons. In an array of Class 2 Bonhoeffer-van der Pol models, in which each neuron had a clear threshold between firing and resting, long lasting transient firing patterns with bursting and irregular motion were observed. PMID- 26829605 TI - A Fast Reduced Kernel Extreme Learning Machine. AB - In this paper, we present a fast and accurate kernel-based supervised algorithm referred to as the Reduced Kernel Extreme Learning Machine (RKELM). In contrast to the work on Support Vector Machine (SVM) or Least Square SVM (LS-SVM), which identifies the support vectors or weight vectors iteratively, the proposed RKELM randomly selects a subset of the available data samples as support vectors (or mapping samples). By avoiding the iterative steps of SVM, significant cost savings in the training process can be readily attained, especially on Big datasets. RKELM is established based on the rigorous proof of universal learning involving reduced kernel-based SLFN. In particular, we prove that RKELM can approximate any nonlinear functions accurately under the condition of support vectors sufficiency. Experimental results on a wide variety of real world small instance size and large instance size applications in the context of binary classification, multi-class problem and regression are then reported to show that RKELM can perform at competitive level of generalized performance as the SVM/LS SVM at only a fraction of the computational effort incurred. PMID- 26829606 TI - [Diffuse Pulmonary Ossification]. AB - Diffuse pulmonary ossification (DPO) represents an uncommon condition usually associated with different underlying pulmonary and extrapulmonary diseases. In this work, we discuss eleven patients of our clinic with the diagnosis of a diffuse pulmonary ossification. We focus on histological changes in the surrounding lung tissue. Clinical and radiological findings were analysed. The aim of the study is to collect data for a better understanding of this condition, especially in association with interstitial lung disease.Three patients with interstitial lung disease had histological findings of UIP. The follow-up data of these patients showed a benign course of the disease.The analysis of the clinical data yielded a very heterogenous group. Regarding these fact we assume, that DPO is not an own entity, but a pathological epiphenomenon in the context of different conditions, possibly with pathogenetic overlap. PMID- 26829607 TI - Hamstring-and-Lower-Back Flexibility in Male Amateur Soccer Players. AB - OBJECTIVE: This study investigated the hamstring-and-lower-back flexibility (HLBF) of male adult amateur soccer players, using the sit-and-reach test (SRT), with a view to obtaining population-based reference values and to determining whether SRT scores are associated with player characteristics. DESIGN: Cross sectional cohort study. SETTING: Teams from high-level Dutch amateur soccer competitions were recruited for participation. PARTICIPANTS: Dutch male high level amateur field soccer players (n = 449) of age 18 to 40 years. Players with a hamstring injury at the moment of SRT-measurement or any other injury that prevented them from following the SRT protocol were excluded. MAIN OUTCOME MEASURES: Sit-and-reach test scores were measured and then population-based reference values were calculated as follows: >2SD below mean (defining "very low" HLBF), 1SD-2SD below mean ("low" HLBF), 1SD below mean to 1SD above mean ("normal" HLBF), 1SD-2SD above mean ("high" HLBF), and >2SD above mean ("very high" HLBF). Whether SRT scores were correlated with player characteristics was determined using a Pearson correlation coefficient or Spearman rho. RESULTS: Sit and-reach test scores ranged from 0 to 43.5 cm (mean 22.0 cm, SD 9.2). The cutoff points for population-based reference values were <3.5 cm for "very low", 3.5 to 13.0 cm for "low", 13.0 to 31.0 cm for "normal", 31.0 to 40.5 cm for "high", and >40.5 cm for "very high". Sit-and-reach test scores were significantly associated with players' height (rho = -0.132, P = 0.005), body mass index (r = 0.114, P = 0.016), and history of anterior cruciate ligament surgery (P < 0.001). CONCLUSIONS: This study is the first to describe the HLBF of amateur soccer players. The SRT reference values with cutoff points may facilitate evidence based decision making regarding HLBF, and the SRT might be a useful tool to assess injury risk, performance, or for diagnostic purposes. PMID- 26829608 TI - Injury Prevention Exercise Programs for Professional Soccer: Understanding the Perceptions of the End-Users. AB - OBJECTIVE: To evaluate the perceptions of professional soccer players and staff members toward injury prevention exercise programs (IPEPs). DESIGN: Self-report survey. SETTING: Four professional soccer teams in 4 different countries. PARTICIPANTS: 126 players, coaches, physiotherapists, and fitness coaches were invited to participate, with 72 respondents. MAIN OUTCOME MEASURES: Web-based survey detailing perceptions of lower limb (LL) injury susceptibility and seriousness, the value of IPEPs in general, and more specifically the International Federation of Association Football (FIFA) 11+. RESULTS: The vast majority of the respondents believed that professional soccer players are at high risk of LL injuries (93%) and that players should perform evidence-based injury prevention exercises (98%). They also agreed that LL injuries can shorten a player's career (85%), cause physical problems later in life (82%), and negatively impact on team performance (77%). However, perceptions varied across teams regarding which types of injury prevention exercises are effective, who holds responsibility for injury prevention, and when IPEPs should be performed. Specific knowledge of the FIFA 11+ was very low and 47% of respondents believed the program would need modification for use in their team. CONCLUSIONS: Players and staff members in professional soccer teams strongly support the use of evidence-based IPEPs. However, perceptions vary considerably between teams regarding which exercises can prevent injuries, who holds the responsibility for injury prevention, and when preventive exercises should be performed. Enhancing the ultimate impact of IPEPs in professional soccer requires a detailed understanding of each team's specific implementation context. PMID- 26829609 TI - Impact of Patellar Tendinopathy on Knee Proprioception: A Cross-Sectional Study. AB - OBJECTIVE: To determine whether high-level athletes with patellar tendinopathy have diminished knee proprioceptive acuity. DESIGN: Cross-sectional study. SETTING: University research laboratory (institutional). PARTICIPANTS: Twenty-one basketball and volleyball players with patellar tendinopathy (13 men and 8 women; mean age 24.5 +/- 3.6; body mass index = 22.5 +/- 2.0 kg/m) and an equal number of athletes without symptoms of patellar tendinopathy injury were included in this study. ASSESSMENTS: Participants underwent knee proprioception assessments on a single day. Furthermore, age, sex, height, weight, VISA-P (Victorian Institute of Sport Assessment) questionnaire sports participation, medical history, knee injuries, previous treatment, and medication were obtained. MAIN OUTCOME MEASURES: Knee proprioception was evaluated by assessing sense of resistance, using a weight discrimination protocol, and joint position sense (JPS). RESULTS: No significant differences were observed in JPS at 30 and 60 degrees of knee flexion between groups (P = 0.165 and 0.481, respectively). In regard to the ability to discriminate weight, significant differences between the 2 groups were found with the tendinopathy group showing a higher percentage of error (P = 0.009), namely when the set of incremental weights varied by 10% from the standard weight. CONCLUSIONS: Athletes with patellar tendinopathy have a diminished perception of force signals required for weight discrimination, whereas JPS remains unaffected in these athletes. PMID- 26829610 TI - Peroneal Nerve Dysfunction due to Multiligament Knee Injury: Patient Characteristics and Comparative Outcomes After Posterior Tibial Tendon Transfer. AB - OBJECTIVE: To objectively compare outcomes of nonoperative management and posterior tibial tendon (PTT) transfer for peroneal nerve injury due to multiligament knee injury (MLI). DESIGN: Retrospective cohort study with prospective follow-up. SETTING: Tertiary care institution. PATIENTS: Ten patients with peroneal nerve injury due to MLI (5 managed nonoperatively, 5 with PTT transfer) were evaluated and a control group of 4 patients without peroneal nerve injury. INTERVENTIONS: Clinical examination, subjective questionnaires, and 3-D motion capture gait analysis during flat-ground walking and stair descent. MAIN OUTCOME MEASURES: The primary outcome measure was the result of gait analysis. The results of subjective questionnaires were a secondary outcome measure. RESULTS: Dorsiflexion was significantly reduced at initial contact and mid-late swing phase in the nonoperative cohort. The PTT transfer cohort demonstrated increased dorsiflexion at each of these time intervals compared with patients managed nonoperatively, restoring symmetry between limbs. The PTT transfer cohort demonstrated similar gait patterns to controls but tended to be more everted. Ground reaction force was increased in the uninvolved limb in the PTT transfer group during gait and step down. There were no statistically significant differences in AOFAS, FAAM, IKDC, or Lysholm results. CONCLUSIONS: Posterior tibial tendon transfer is an option to restore dorsiflexion and eliminate the need for an orthosis in patients with foot drop due to MLI. Gait analysis demonstrates a significant improvement in sagittal plane ankle kinematics after PTT transfer. The trade-off is subtle instability, highlighting the dynamic stability that the PTT provides. PMID- 26829611 TI - Reliability Testing of the Balance Error Scoring System in Children Between the Ages of 5 and 14. AB - OBJECTIVE: Pediatric concussion is an extensive public health concern with a complex clinical presentation. Balance assessment has been well-studied in the adult population, but has been limited in children. We aimed to assess the reliability and minimum detectable change (MDC) of the Balance Error Scoring System (BESS) in healthy children. DESIGN: This prospective observational study included 373 healthy children aged 5 to 14. Interrater reliability was assessed by having 4 assessors review videos of 50 random subjects distributed evenly by age and sex across the entire cohort. Intrarater reliability was performed by having assessors review videos of other assessors' live evaluations. Test-retest reliability was obtained by comparing BESS scores as recorded live at the 2 separate time points by the same rater. SETTING: Local elementary and junior high schools. PARTICIPANTS: Three hundred and seventy three healthy children between the ages of 5 and 14. INTERVENTIONS: The BESS was performed on all children. MAIN OUTCOME MEASURES: Intraclass Correlation Coefficients (ICCs) and MDC Scores. RESULTS: The overall interrater ICC was determined to be 0.93 [95% confidence interval (CI), 0.79-0.97] and intrarater ICC was 0.96 (95% CI, 0.95-0.97) with individual intrarater ICCs ranging between 0.69 and 0.99. The test-retest reliability was 0.90 (95% CI, 0.88-0.92). The MDCs were 9.6, 4.6, and 7.3 points at the 95% CIs for interrater, intrarater, and test-retest comparisons, respectively. No learning effect was seen. CONCLUSIONS: The BESS demonstrates excellent reliability in the pediatric population without evidence of a learning effect. PMID- 26829612 TI - Examining Radiation-Induced In Vivo and In Vitro Gene Expression Changes of the Peripheral Blood in Different Laboratories for Biodosimetry Purposes: First RENEB Gene Expression Study. AB - The risk of a large-scale event leading to acute radiation exposure necessitates the development of high-throughput methods for providing rapid individual dose estimates. Our work addresses three goals, which align with the directive of the European Union's Realizing the European Network of Biodosimetry project (EU RENB): 1. To examine the suitability of different gene expression platforms for biodosimetry purposes; 2. To perform this examination using blood samples collected from prostate cancer patients (in vivo) and from healthy donors (in vitro); and 3. To compare radiation-induced gene expression changes of the in vivo with in vitro blood samples. For the in vitro part of this study, EDTA treated whole blood was irradiated immediately after venipuncture using single X ray doses (1 Gy/min(-1) dose rate, 100 keV). Blood samples used to generate calibration curves as well as 10 coded (blinded) samples (0-4 Gy dose range) were incubated for 24 h in vitro, lysed and shipped on wet ice. For the in vivo part of the study PAXgene tubes were used and peripheral blood (2.5 ml) was collected from prostate cancer patients before and 24 h after the first fractionated 2 Gy dose of localized radiotherapy to the pelvis [linear accelerator (LINAC), 580 MU/min, exposure 1-1.5 min]. Assays were run in each laboratory according to locally established protocols using either microarray platforms (2 laboratories) or qRT-PCR (2 laboratories). Report times on dose estimates were documented. The mean absolute difference of estimated doses relative to the true doses (Gy) were calculated. Doses were also merged into binary categories reflecting aspects of clinical/diagnostic relevance. For the in vitro part of the study, the earliest report time on dose estimates was 7 h for qRT-PCR and 35 h for microarrays. Methodological variance of gene expression measurements (CV <=10% for technical replicates) and interindividual variance (<=twofold for all genes) were low. Dose estimates based on one gene, ferredoxin reductase (FDXR), using qRT-PCR were as precise as dose estimates based on multiple genes using microarrays, but the precision decreased at doses >=2 Gy. Binary dose categories comprising, for example, unexposed compared with exposed samples, could be completely discriminated with most of our methods. Exposed prostate cancer blood samples (n = 4) could be completely discriminated from unexposed blood samples (n = 4, P < 0.03, two-sided Fisher's exact test) without individual controls. This could be performed by introducing an in vitro-to-in vivo correction factor of FDXR, which varied among the laboratories. After that the in vitro-constructed calibration curves could be used for dose estimation of the in vivo exposed prostate cancer blood samples within an accuracy window of +/-0.5 Gy in both contributing qRT-PCR laboratories. In conclusion, early and precise dose estimates can be performed, in particular at doses <=2 Gy in vitro. Blood samples of prostate cancer patients exposed to 0.09-0.017 Gy could be completely discriminated from pre-exposure blood samples with the doses successfully estimated using adjusted in vitro constructed calibration curves. PMID- 26829614 TI - Prediction of the metabolic clearance of benzophenone-2, and its interaction with isoeugenol and coumarin using cryopreserved human hepatocytes in primary culture. AB - Benzophenone-2 (BP2) is widely used as a UV screen in both industrial products and cosmetic formulations, where it is frequently found associated with fragrance compounds, such as isoeugenol and coumarin. BP2 is now recognized as an endocrine disruptor, but to date, no information has been reported on its fate in humans. The intrinsic clearance (Clint) and metabolic interactions of BP2 were explored using cryopreserved human hepatocytes in primary cultures. In vitro kinetic experiments were performed to estimate the Michaelis-Menten parameters. The substrate depletion method demonstrated that isoeugenol was cleared more rapidly than BP2 or coumarin (Clint = 259, 94.7 and 0.40 MUl/min/10(6) cells respectively). This vitro model was also used to study the metabolic interactions between BP2 and isoeugenol and coumarin. Coumarin exerted no effects on either isoeugenol or BP2 metabolism, because of its independent metabolic pathway (CYP2A6). Isoeugenol appeared to be a potent competitive substrate inhibitor of BP2 metabolism, equivalent to the specific UGT1A1 substrate: estradiol. Despite the fact that inhibition of UGT by xenobiotics is not usually considered to be a major concern, the involvement of UGT1A1 in BP2 metabolism may have pharmacokinetic and pharmacological consequences, due to the its polymorphisms in humans and its pure estrogenic effect. PMID- 26829613 TI - Characterization of the C-Terminal Nuclease Domain of Herpes Simplex Virus pUL15 as a Target of Nucleotidyltransferase Inhibitors. AB - The natural product alpha-hydroxytropolones manicol and beta-thujaplicinol inhibit replication of herpes simplex viruses 1 and 2 (HSV-1 and HSV-2, respectively) at nontoxic concentrations. Because these were originally developed as divalent metal-sequestering inhibitors of the ribonuclease H activity of HIV-1 reverse transcriptase, alpha-hydroxytropolones likely target related HSV proteins of the nucleotidyltransferase (NTase) superfamily, which share an "RNase H-like" fold. One potential candidate is pUL15, a component of the viral terminase molecular motor complex, whose C-terminal nuclease domain, pUL15C, has recently been crystallized. Crystallography also provided a working model for DNA occupancy of the nuclease active site, suggesting potential protein-nucleic acid contacts over a region of ~ 14 bp. In this work, we extend crystallographic analysis by examining pUL15C-mediated hydrolysis of short, closely related DNA duplexes. In addition to defining a minimal substrate length, this strategy facilitated construction of a dual-probe fluorescence assay for rapid kinetic analysis of wild-type and mutant nucleases. On the basis of its proposed role in binding the phosphate backbone, studies with pUL15C variant Lys700Ala showed that this mutation affected neither binding of duplex DNA nor binding of small molecule to the active site but caused a 17-fold reduction in the turnover rate (kcat), possibly by slowing conversion of the enzyme-substrate complex to the enzyme-product complex and/or inhibiting dissociation from the hydrolysis product. Finally, with a view of pUL15-associated nuclease activity as an antiviral target, the dual-probe fluorescence assay, in combination with differential scanning fluorimetry, was used to demonstrate inhibition by several classes of small molecules that target divalent metal at the active site. PMID- 26829615 TI - Modulating effect of simvastatin on the DNA damage induced by doxorubicin in somatic cells of Drosophila melanogaster. AB - Simvastatin is an antilipemic drug that promotes inhibition of HMG-CoA reductase. Simvastatin can also inhibit the formation of other products, such as isoprenoids, conferring additional benefits to this drug, which include antiproliferative, anti-invasive and pro-apoptotic effects. This study was carried out with the aim of evaluating the mutagenic/recombinogenic effect of simvastatin as well as the possible modulatory effects of this statin on the DNA damage induced by doxorubicin (DXR). This analysis was performed using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. To study these effects, larvae descendants of both crosses (ST and HB) were chronically treated with five concentrations of simvastatin, separately and in association with DXR. The results revealed no mutagenic/recombinogenic effect of simvastatin for any of the concentrations tested. A modulating effect of simvastatin was also observed on DNA damage induced by DXR. The reduction of total mutant frequency was observed for spots from descendants of both crosses, but the inhibition was more effective in descendants from the standard cross (ST). It is believed that this modulating effect is mainly associated with the antioxidant activity of this class of drugs, although this parameter has not been directly assessed in this study. PMID- 26829617 TI - Highly Selective and Efficient Removal of Heavy Metals by Layered Double Hydroxide Intercalated with the MoS4(2-) Ion. AB - The MoS4(2-) ion was intercalated into magnesium-aluminum layered double hydroxide (MgAl-NO3-LDH) to produce a single phase material of Mg0.66Al0.34(OH)2(MoS4)0.17.nH2O (MgAl-MoS4-LDH), which demonstrates highly selective binding and extremely efficient removal of heavy metal ions such as Cu(2+), Pb(2+), Ag(+), and Hg(2+). The MoS4-LDH displays a selectivity order of Co(2+), Ni(2+), Zn(2+) < Cd(2+) ? Pb(2+) < Cu(2+) < Hg(2+) < Ag(+) for the metal ions. The enormous capacities for Hg(2+) (~500 mg/g) and Ag(+) (450 mg/g) and very high distribution coefficients (Kd) of ~10(7) mL/g place the MoS4-LDH at the top of materials known for such removal. Sorption isotherm for Ag(+) agrees with the Langmuir model suggesting a monolayer adsorption. It can rapidly lower the concentrations of Cu(2+), Pb(2+), Hg(2+), and Ag(+) from ppm levels to trace levels of <=1 ppb. For the highly toxic Hg(2+) (at ~30 ppm concentration), the adsorption is exceptionally rapid and highly selective, showing a 97.3% removal within 5 min, 99.7% removal within 30 min, and ~100% removal within 1 h. The sorption kinetics for Cu(2+), Ag(+), Pb(2+), and Hg(2+) follows a pseudo-second order model suggesting a chemisorption with the adsorption mechanism via M-S bonding. X-ray diffraction patterns of the samples after adsorption demonstrate the coordination and intercalation structures depending on the metal ions and their concentration. After the capture of heavy metals, the crystallites of the MoS4-LDH material retain the original hexagonal prismatic shape and are stable at pH ~ 2-10. The MoS4-LDH material is thus promising for the remediation of heavy metal polluted water. PMID- 26829616 TI - RIFM fragrance ingredient safety assessment, alpha-Methylbenzyl acetate, CAS Registry Number 93-92-5. AB - The use of this material under current use conditions is supported by the existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity, skin sensitization potential, as well as, environmental safety. Developmental toxicity was determined to have the most conservative systemic exposure derived NO[A]EL of 100 mg/kg/day. A gavage developmental toxicity study conducted in rats on a suitable read across analog resulted in aMOE of 3571 while considering 78.7% absorption from skin contact and 100% from inhalation. A MOE of >100 is deemed acceptable. PMID- 26829618 TI - Separation of [(99m)Tc]pertechnetate and molybdate using polyethylene glycol coated C18 and C30 resins. AB - Hydrophobic adsorbents such as C18 and C30 were coated with PEG and subsequently used for the separation of Mo/Tc. The most effective resin for adsorbing PEG was the C18-U resin, which demonstrated a coating capacity of 97.6+/-2.8mg PEG per g of resin. The ability to adsorb pertechnetate was proportional to the amount of PEG coated on the hydrophobic resin. The [(99m)Tc]pertechnetate recovery during the separation of cyclotron produced (99m)Tc from (100)Mo was 91.8+/-0.3% (n=2). The resultant product met relevant USP monograph specifications. PMID- 26829619 TI - Naphthalene Tetracarboxydiimide-Based n-Type Polymers with Removable Solubility via Thermally Cleavable Side Chains. AB - Multilayer solution-processed devices in organic electronics show the tendency of intermixing of subsequently deposited layers. Here, we synthesize naphthalene tetracarboxydiimide (NDI)-based n-type semiconducting polymers with thermally cleavable side chains which upon removal render the polymer insoluble. Infrared and photoelectron spectroscopy were performed to investigate the pyrolysis process. Characterization of organic field-effect transistors provides insight into charge transport. After the pyrolysis homogeneous films could be produced which are insoluble in the primary solvent. By varying curing temperature and time we show that these process parameters govern the amount of side chains in the film and influence the device performance. PMID- 26829620 TI - PM-IRRAS Studies of DMPC Bilayers Supported on Au(111) Electrodes Modified with Hydrophilic Monolayers of Thioglucose. AB - A phospholipid bilayer composed of 1,2-dimyristoyl-d54-sn-glycero-3 phosphocholine (d54-DMPC) was deposited onto the Au(111) electrode modified with a self-assembled monolayer of 1-thio-beta-d-glucose (beta-Tg) via the Langmuir Blodgett and Langmuir-Schaefer (LB-LS) techniques. Polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) measurements were used to characterize structural and orientational changes in this model biological membrane on a hydrophilic surface modified gold electrode. The results of the spectroscopic measurements showed that the tilt angle of acyl chains obtained for deuterated DMPC bilayers supported on the beta-Tg-modified gold is significantly lower than that reported previously for DMPC bilayers deposited directly on Au(111) electrodes. Moreover, tilt angles of ~18 degrees were obtained for d54 DMPC bilayers on beta-Tg self-assembled monolayers (SAMs) at positive potentials, which are similar to the values calculated for h-DMPC deposited on bare gold in the desorbed state and to those observed for a stack of hydrated DMPC bilayers. This data confirms that the beta-thioglucose SAM promotes the formation of a water cushion that separates the phospholipid bilayer from the metal surface. As a result, the DMPC polar heads are not in direct contact with the electrode and can adopt a zigzag configuration, which strengthens the chain-chain interactions and allows for an overall decrease in the tilt of the acyl chains. These novel supported model membranes may be especially useful in studies pertaining to the incorporation of peptides and proteins into phospholipid bilayers. PMID- 26829621 TI - Training the next generation of biomedical investigators in glycosciences. AB - This position statement originated from a working group meeting convened on April 15, 2015, by the NHLBI and incorporates follow-up contributions by the participants as well as other thought leaders subsequently consulted, who together represent research fields relevant to all branches of the NIH. The group was deliberately composed not only of individuals with a current research emphasis in the glycosciences, but also of many experts from other fields, who evinced a strong interest in being involved in the discussions. The original goal was to discuss the value of creating centers of excellence for training the next generation of biomedical investigators in the glycosciences. A broader theme that emerged was the urgent need to bring the glycosciences back into the mainstream of biology by integrating relevant education into the curricula of medical, graduate, and postgraduate training programs, thus generating a critical sustainable workforce that can advance the much-needed translation of glycosciences into a more complete understanding of biology and the enhanced practice of medicine. PMID- 26829622 TI - Recent developments in the effort to cure HIV infection: going beyond N = 1. AB - Combination antiretroviral therapy (ART) can suppress plasma HIV to undetectable levels, allowing HIV-infected individuals who are treated early a nearly normal life span. Despite the clear ability of ART to prevent morbidity and mortality, it is not curative. Even in individuals who have full suppression of viral replication on ART, there are resting memory CD4+ T cells that harbor stably integrated HIV genomes, which are capable of producing infectious virus upon T cell activation. This latent viral reservoir is considered the primary obstacle to the development of an HIV cure, and recent efforts in multiple areas of HIV research have been brought to bear on the development of strategies to eradicate or develop a functional cure for HIV. Reviews in this series detail progress in our understanding of the molecular and cellular mechanisms of viral latency, efforts to accurately assess the size and composition of the latent reservoir, the characterization and development of HIV-targeted broadly neutralizing antibodies and cytolytic T lymphocytes, and animal models for the study HIV latency and therapeutic strategies. PMID- 26829623 TI - In vivo platforms for analysis of HIV persistence and eradication. AB - HIV persistence in patients undergoing antiretroviral therapy is a major impediment to the cure of HIV/AIDS. The molecular and cellular mechanisms underlying HIV persistence in vivo have not been fully elucidated. This lack of basic knowledge has hindered progress in this area. The in vivo analysis of HIV persistence and the implementation of curative strategies would benefit from animal models that accurately recapitulate key aspects of the human condition. This Review summarizes the contribution that humanized mouse models of HIV infection have made to the field of HIV cure research. Even though these models have been shown to be highly informative in many specific areas, their great potential to serve as excellent platforms for discovery in HIV pathogenesis and treatment has yet to be fully developed. PMID- 26829626 TI - Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice. PMID- 26829624 TI - The role of HIV integration in viral persistence: no more whistling past the proviral graveyard. AB - A substantial research effort has been directed to identifying strategies to eradicate or control HIV infection without a requirement for combination antiretroviral therapy (cART). A number of obstacles prevent HIV eradication, including low-level viral persistence during cART, long-term persistence of HIV infected cells, and latent infection of resting CD4+ T cells. Mechanisms of persistence remain uncertain, but integration of the provirus into the host genome represents a central event in replication and pathogenesis of all retroviruses, including HIV. Analysis of HIV proviruses in CD4+ lymphocytes from individuals after prolonged cART revealed that a substantial proportion of the infected cells that persist have undergone clonal expansion and frequently have proviruses integrated in genes associated with regulation of cell growth. These data suggest that integration may influence persistence and clonal expansion of HIV-infected cells after cART is introduced, and these processes may represent key mechanisms for HIV persistence. Determining the diversity of host genes with integrants in HIV-infected cells that persist for prolonged periods may yield useful information regarding pathways by which infected cells persist for prolonged periods. Moreover, many integrants are defective, and new studies are required to characterize the role of clonal expansion in the persistence of replication-competent HIV. PMID- 26829625 TI - Measuring the latent reservoir in vivo. AB - Current efforts toward achieving a cure for HIV are focused on developing strategies to eliminate latently infected CD4+ T cells, which represent the major barrier to virus eradication. Sensitive, precise, and practical assays that can reliably characterize and measure this HIV reservoir and can reliably measure the impact of a candidate treatment strategy are essential. PCR-based procedures for detecting integrated HIV DNA will overestimate the size of the reservoir by detecting replication-incompetent proviruses; however, viral outgrowth assays underestimate the size of the reservoir. Here, we describe the attributes and limitations of current procedures for measuring the HIV reservoir. Characterizing their relative merits will require rigorous evaluation of their performance characteristics (sensitivity, specificity, reproducibility, etc.) and their relationship to the results of clinical studies. PMID- 26829627 TI - Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production. PMID- 26829628 TI - Serum amyloid A impairs the antiinflammatory properties of HDL. PMID- 26829629 TI - MULTIMETHOD FACTOR ANALYSIS: A REFORMULATION. AB - A method is proposed for the evaluation of the degree to which trait measures show stability across diverse methods of measurement. Each mono method block is separately factored and orthogonally rotated so that only one trait measure is highly loaded on a given dimension. The component score intercorrelation matrix is computed implicitly, and this matrix is re-factored and rotated by varimax. The technique is illustrated using multitrait-multimethod matrices from personality assessment, which yield trait-specific factors. By reversing the procedure and separately factoring monotrait-heteromethod blocks followed by the re-factoring of implicit component scores, it is demonstrated that method factors may be isolated. PMID- 26829630 TI - Between, Within, and Total Group Factor Analyses of Student Ratings of Instruction. AB - The purpose of this study was to compare the factor structures of student ratings of instruction resulting from total group, between group, and within group analyses. Six factors obtained from responses by 9700 students to 31 items were used to approximate the between group covariance matrix based on 43'7 classroom means and the pooled within classroom covariance matrix. A good approximation to both the between and within group covariance matrices was obtained. PMID- 26829631 TI - On the Empirical Relation Between Spatial Ability and Sex Differences in Other Aspects of Cognitive Performance. AB - The hypothesis that sex differences in field independence and mental arithmetic can be accounted for by sex differences in spatial ability was supported for a group of 46 female and 35 male undergraduates. Sex-typing does not appear to be strongly related to spatial ability for either sex. There is a possibility of the existence of a field-independence trait independent of spatial ability, particularly among females; however, if such a trait does exist there do not appear to be significant sex differences with respect to it. Factor analysis indicates that tests of spatial ability, field independence, and mental arithmetic emerge together in a spatial ability factor. Sex differences in the factor structure of nine measures, most of which typically display sex differences (spatial ability, field independence, mental arithmetic, vocabulary, verbal and nonverbal creativity, femininity, and achievement motivation) were largely the result of differences with respect to a spatial factor. PMID- 26829632 TI - Detection Of Faking on the Comrey Personality Scales. AB - The ability of subjects to fake responses on personality tests under various experimental conditions has been established in several studies, including those involving the Comrey Personality Scales (CPS). Evidence is presented in this study regarding the potential of several techniques for detecting faked CPS test records, along with a further demonstration of the extent to which the CPS can be faked. Five groups of test records were used: four were from two sets of university student subjects, with one test record completed under normal conditions and the other under instructions to deliberately "fake good." The final group of CPS records was from a set of police officer candidates. Several possible faking predictor scores were related to a continuously measured index of faking based on differences between "faked" and "normal" records and also to a dichotomous criterion of faking. Results of a correlational analysis show that the best predictor of faking on the Comrey Personality Scales is a total summary score obtained by adding up all ten CPS scale scores. PMID- 26829633 TI - Empirical Sampling Distributions of the Product Moment Correlation Coefficient When Bivariate Observations are Correlated. AB - In some correlational studies it is not reasonable to assume that bivariate observations are uncorrelated. An example would be a configural analysis in which two individuals are correlated across several variables (e.g. Q-technique). The present study was a Monte Carlo investigation of the robustness of techniques used in judging the magnitude of a sample correlation coefficient when observations are correlated. Empirical distributions of r, t, and Fisher's x were generated. Patterns of correlation were found which caused error rates to be as high as .20 when the nominal alpha was .05. A technique for controlling error rates in certain situations is suggested. PMID- 26829634 TI - Validation of the State-Trait Distinction in Anxiety Research. AB - High school and university students were given Sarason's Test Anxiety Scale for Children, an intelligence test, and the A-State and A-Trait Scales of Spielberger's State-Trait Anxiety Inventory (STAI). The STAI A-Stake Scale was administered under one non-stress and two stress conditions to both groups of subjects. A factor analysis of the data for the high school students identified six factors: trait anxiety; t h e e separate state anxiety factors, corresponding to each of the three administrations of the A-State Scale; a reversed-item factor; and an ability factor. A similar factor pattern emerged for the university students. The results were interpreted as providing evidence of the importance of situational stress in evoking anxiety states, and strong support for the slate-trait distinction in anxiety research. PMID- 26829635 TI - Simultaneous Contrast Testing Procedures for Multivariate Experiments. AB - Simultaneous test procedures associated with multivariate analysis of variance provide very little power for tests of contrasts written on individual variates or on planned linear combinations of variates. Generalizations of the Scheffe, Tukey, and Bonferroni-t techniques are presented, each of which controls the experimentwise error rate for a particular type of partially or fully planned analysis. All three procedures provide more power than MANOVA tests. PMID- 26829636 TI - A Monte Carlo Study of the Stability of Canonical Correlations, Canonical Weights and Canonical Variate-Variable Correlations. AB - A Monte Carlo study was run to check the stability of canonical correlations, canonical weights, and canonical variate-variable correlations. Eight data matrices were selected from the literature for the canonical analyses, with the number of variables ranging from 7 to 41. The results showed that the canonical correlations are very stable upon replication. The results also indicated that there is no solid evidence for concluding that the components are superior to the coefficients, a t least not in terms of being more reliable. However, the number of subjects per variable necessary to achieve re1i:tbility in detecting the most important variables, using components or coefficients, was quite large, ranging from 42/1 to 68/1. PMID- 26829637 TI - An Inferential Strategy for Determining Factor Invariance Across Different Individuals and Different Variables. AB - Different methods for indirectly establishing factor invariance across two situations both involving different individuals and different situations are out- lined. The procedures involve a planned data gathering strategy consisting of a t least two different groups, each receiving two different test batteries. The recommended strategy involves a combination of Tucker's interbattery technique and congruence measures. Some of the limitations of the concept of factor invariance are briefly discussed. It is concluded that statistical measures of factor invariance are a necessary but not a sufficient condition for the psycho- logical invariance of constructs accounting for individual differences. PMID- 26829638 TI - Regions of Significance in Multiple Regression Analysis. AB - There has been frequent confusion about the meaning of the various possible tests of significance in multiple regression, and this has led to discussions of "apparent contradictions" in regression. This paper considers the case of two predictor variables, and figures are obtained which show the regions of significance of joint regression coefficients, regression coefficients considered separately, and the multiple correlation. The intersection of these regions of significance and non-significance illustrates how the various "apparent contra- dictions" and anomalies may occur. PMID- 26829639 TI - Travel Time Estimation Using Freeway Point Detector Data Based on Evolving Fuzzy Neural Inference System. AB - Travel time is an important measurement used to evaluate the extent of congestion within road networks. This paper presents a new method to estimate the travel time based on an evolving fuzzy neural inference system. The input variables in the system are traffic flow data (volume, occupancy, and speed) collected from loop detectors located at points both upstream and downstream of a given link, and the output variable is the link travel time. A first order Takagi-Sugeno fuzzy rule set is used to complete the inference. For training the evolving fuzzy neural network (EFNN), two learning processes are proposed: (1) a K-means method is employed to partition input samples into different clusters, and a Gaussian fuzzy membership function is designed for each cluster to measure the membership degree of samples to the cluster centers. As the number of input samples increases, the cluster centers are modified and membership functions are also updated; (2) a weighted recursive least squares estimator is used to optimize the parameters of the linear functions in the Takagi-Sugeno type fuzzy rules. Testing datasets consisting of actual and simulated data are used to test the proposed method. Three common criteria including mean absolute error (MAE), root mean square error (RMSE), and mean absolute relative error (MARE) are utilized to evaluate the estimation performance. Estimation results demonstrate the accuracy and effectiveness of the EFNN method through comparison with existing methods including: multiple linear regression (MLR), instantaneous model (IM), linear model (LM), neural network (NN), and cumulative plots (CP). PMID- 26829640 TI - Caregiver burden in Danish family members of patients with severe brain injury: The chronic phase. AB - OBJECTIVE: To investigate caregiver burden and factors associated with caregiver burden among family members of patients with severe brain injury in the chronic phase. Additionally, the study aimed at investigating differences in burden between parents and spouses. METHODS: Forty-four Danish caregivers of patients with severe brain injury were contacted 3-6 years post-injury and asked to complete a measure of caregiver burden. RESULTS: Medium, high and low levels of burden were observed in 45%, 16% and 39% of family members, respectively. Higher burden was seen in caregivers of patients with more severe injuries, who spent more time on caregiving and reported more unmet needs. Overall, spouses spent significantly more time taking care of their family member than parents and reported higher levels of burden. CONCLUSIONS: The findings emphasized the continuing consequences of brain injury on not only the individual with the brain injury, but also on the surrounding family. Spouses, caregivers of patients with more severe injuries, who spent more time on caregiving and reported more unmet needs experienced higher levels of burden in the chronic phase. Future intervention programmes should target such specific caregivers, who might need more support and long-lasting help. PMID- 26829641 TI - Veterans' Perspectives on Interventions to Improve Retention in HIV Care. AB - Poor retention in HIV medical care is associated with increased mortality among patients with HIV/AIDS. Developing new interventions to improve retention in HIV primary care is needed. The Department of Veteran Affairs (VA) is the largest single provider of HIV care in the US. We sought to understand what veterans would want in an intervention to improve retention in VA HIV care. We conducted 18 one-on-one interviews and 15 outpatient focus groups with 46 patients living with HIV infection from the Michael E. DeBakey VAMC (MEDVAMC). Analysis identified three focus areas for improving retention in care: developing an HIV friendly clinic environment, providing mental health and substance use treatment concurrent with HIV care and encouraging peer support from other Veterans with HIV. PMID- 26829642 TI - Decreased Bone Formation Explains Osteoporosis in a Genetic Mouse Model of Hemochromatosiss. AB - Osteoporosis may complicate iron overload diseases such as genetic hemochromatosis. However, molecular mechanisms involved in the iron-related osteoporosis remains poorly understood. Recent in vitro studies support a role of osteoblast impairment in iron-related osteoporosis. Our aim was to analyse the impact of excess iron in Hfe-/- mice on osteoblast activity and on bone microarchitecture. We studied the bone formation rate, a dynamic parameter reflecting osteoblast activity, and the bone phenotype of Hfe-/- male mice, a mouse model of human hemochromatosis, by using histomorphometry. Hfe-/- animals were sacrificed at 6 months and compared to controls. We found that bone contains excess iron associated with increased hepatic iron concentration in Hfe-/- mice. We have shown that animals with iron overload have decreased bone formation rate, suggesting a direct impact of iron excess on active osteoblasts number. For bone mass parameters, we showed that iron deposition was associated with bone loss by producing microarchitectural impairment with a decreased tendency in bone trabecular volume and trabecular number. A disorganization of trabecular network was found with marrow spaces increased, which was confirmed by enhanced trabecular separation and star volume of marrow spaces. These microarchitectural changes led to a loss of connectivity and complexity in the trabecular network, which was confirmed by decreased interconnectivity index and increased Minkowski's fractal dimension. Our results suggest for the first time in a genetic hemochromatosis mouse model, that iron overload decreases bone formation and leads to alterations in bone mass and microarchitecture. These observations support a negative effect of iron on osteoblast recruitment and/or function, which may contribute to iron-related osteoporosis. PMID- 26829643 TI - Biology of GDNF and its receptors - Relevance for disorders of the central nervous system. AB - A targeted effort to identify novel neurotrophic factors for midbrain dopaminergic neurons resulted in the isolation of GDNF (glial cell line-derived neurotrophic factor) from the supernatant of a rat glial cell line in 1993. Over two decades and 1200 papers later, the GDNF ligand family and their different receptor systems are now recognized as one of the major neurotrophic networks in the nervous system, important for the development, maintenance and function of a variety of neurons and glial cells. The many ways in which the four members of the GDNF ligand family can signal and function allow these factors to take part in the control of multiple types of processes, from neuronal survival to axon guidance and synapse formation in the developing nervous system, to synaptic function and regenerative responses in the adult. In this review, we will briefly summarize basic aspects of GDNF signaling mechanisms and receptor systems and then review our current knowledge of the physiology of GDNF activities in the central nervous system, with an eye to its relevance for neurodegenerative and neuropsychiatric diseases. PMID- 26829645 TI - EDISON-WMW: Exact Dynamic Programing Solution of the Wilcoxon-Mann-Whitney Test. AB - In many research disciplines, hypothesis tests are applied to evaluate whether findings are statistically significant or could be explained by chance. The Wilcoxon-Mann-Whitney (WMW) test is among the most popular hypothesis tests in medicine and life science to analyze if two groups of samples are equally distributed. This nonparametric statistical homogeneity test is commonly applied in molecular diagnosis. Generally, the solution of the WMW test takes a high combinatorial effort for large sample cohorts containing a significant number of ties. Hence, P value is frequently approximated by a normal distribution. We developed EDISON-WMW, a new approach to calculate the exact permutation of the two-tailed unpaired WMW test without any corrections required and allowing for ties. The method relies on dynamic programing to solve the combinatorial problem of the WMW test efficiently. Beyond a straightforward implementation of the algorithm, we presented different optimization strategies and developed a parallel solution. Using our program, the exact P value for large cohorts containing more than 1000 samples with ties can be calculated within minutes. We demonstrate the performance of this novel approach on randomly-generated data, benchmark it against 13 other commonly-applied approaches and moreover evaluate molecular biomarkers for lung carcinoma and chronic obstructive pulmonary disease (COPD). We found that approximated P values were generally higher than the exact solution provided by EDISON-WMW. Importantly, the algorithm can also be applied to high-throughput omics datasets, where hundreds or thousands of features are included. To provide easy access to the multi-threaded version of EDISON-WMW, a web-based solution of our algorithm is freely available at http://www.ccb.uni saarland.de/software/wtest/. PMID- 26829644 TI - Loss of Function of Intestinal IL-17 and IL-22 Producing Cells Contributes to Inflammation and Viral Persistence in SIV-Infected Rhesus Macaques. AB - In HIV/SIV-infected humans and rhesus macaques (RMs), a severe depletion of intestinal CD4(+) T-cells producing interleukin IL-17 and IL-22 associates with loss of mucosal integrity and chronic immune activation. However, little is known about the function of IL-17 and IL-22 producing cells during lentiviral infections. Here, we longitudinally determined the levels and functions of IL-17, IL-22 and IL-17/IL-22 producing CD4(+) T-cells in blood, lymph node and colorectum of SIV-infected RMs, as well as how they recover during effective ART and are affected by ART interruption. Intestinal IL-17 and IL-22 producing CD4(+) T-cells are polyfunctional in SIV-uninfected RMs, with the large majority of cells producing four or five cytokines. SIV infection induced a severe dysfunction of colorectal IL-17, IL-22 and IL-17/IL-22 producing CD4(+) T-cells, the extent of which associated with the levels of immune activation (HLA DR(+)CD38(+)), proliferation (Ki-67+) and CD4(+) T-cell counts before and during ART. Additionally, Th17 cell function during ART negatively correlated with residual plasma viremia and levels of sCD163, a soluble marker of inflammation and disease progression. Furthermore, IL-17 and IL-22 producing cell frequency and function at various pre, on, and off-ART experimental points associated with and predicted total SIV-DNA content in the colorectum and blood. While ART restored Th22 cell function to levels similar to pre-infection, it did not fully restore Th17 cell function, and all cell types were rapidly and severely affected -both quantitatively and qualitatively--after ART interruption. In conclusion, intestinal IL-17 producing cell function is severely impaired by SIV infection, not fully normalized despite effective ART, and strongly associates with inflammation as well as SIV persistence off and on ART. As such, strategies able to preserve and/or regenerate the functions of these CD4(+) T-cells central for mucosal immunity are critically needed in future HIV cure research. PMID- 26829646 TI - The impact of psychotherapy treatments of different length and type on health behaviour during a five-year follow-up. AB - OBJECTIVE: The aim of this study was to investigate the influence of psychotherapy treatments of different lengths, number of sessions, and type on health behaviour. METHOD: A total of 367 patients were monitored for their health behaviour (alcohol consumption, body mass index), serum cholesterol (total and HDL), smoking and exercise) for five years from the start of the therapy. The effectiveness of solution-focused therapy, short-term psychodynamic psychotherapy, and long-term psychodynamic psychotherapy (LPP) was examined in a randomized clinical trial, while the LPP group and the non-randomized psychoanalysis (PA) group were compared in a naturalistic design. RESULTS: During the follow-up, an improvement was seen with regard to alcohol consumption, serum HDL cholesterol, and smoking in the LPP and PA groups. No notable differences in health behaviour between the two groups were found, however. During the last two years of the follow-up, changes towards higher alcohol consumption and higher total serum cholesterol levels were observed in the short-term therapy groups. CONCLUSIONS: The impact of PA and LPP on health behaviour did not differ, whereas the changes were less health promoting in short-term psychotherapy. Large-scale studies are needed to confirm these findings. PMID- 26829647 TI - Safety and Efficacy of Gevokizumab in Patients with Behcet's Disease Uveitis: Results of an Exploratory Phase 2 Study. AB - PURPOSE: To evaluate the safety and efficacy of gevokizumab for the treatment of Behcet's disease uveitis in a prospective, open-label, randomized phase 2 trial. METHODS: Behcet's disease patients with new acute ocular exacerbation or at risk of exacerbation received 30 or 60 mg gevokizumab every 4 weeks intravenously or subcutaneously, on top of a stable regimen of immunosuppressives and corticosteroids (<=20 mg/day equivalent prednisolone). Patients withdrew in cases of ocular exacerbation. RESULTS: A total of 21 patients were included (17 acute and 4 at-risk; mean duration of uveitis 45.6 +/- 37.4 months). There were no serious adverse events related to gevokizumab. Recorded adverse events were mostly associated with exacerbation of uveitis or its complications. Response was evaluated for 14 acute patients and all showed rapid control of acute ocular exacerbation, mostly within 1 week, without any increase in corticosteroid dosage. CONCLUSIONS: Gevokizumab was well tolerated and rapidly controlled acute ocular exacerbations of Behcet's disease uveitis without the need for high-dose corticosteroid. PMID- 26829648 TI - Mycobacterium tuberculosis AtsG (Rv0296c), GlmU (Rv1018c) and SahH (Rv3248c) Proteins Function as the Human IL-8-Binding Effectors and Contribute to Pathogen Entry into Human Neutrophils. AB - Mycobacterium tuberculosis is an extremely successful intracellular pathogen that has evolved a broad spectrum of pathogenic mechanisms that enable its manipulation of host defense elements and its survival in the hostile environment inside phagocytes. Cellular influx into the site of mycobacterial entry is mediated by a variety of chemokines, including interleukin-8 (IL-8), and the innate cytokine network is critical for the development of an adaptive immune response and infection control. Using affinity chromatography, liquid chromatography electrospray ionization tandem mass spectrometry and surface plasmon resonance techniques, we identified M. tuberculosis AtsG arylsulphatase, bifunctional glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1 phosphate uridyl transferase (GlmU) and S-adenosyl-L-homocysteine hydrolase (SahH) as the pathogen proteins that bind to human IL-8. The interactions of all of the identified proteins (AtsG, GlmU and SahH) with IL-8 were characterized by high binding affinity with KD values of 6.83x10-6 M, 5.24x10-6 M and 7.14x10-10 M, respectively. Furthermore, the construction of Mtb mutant strains overproducing AtsG, GlmU or SahH allowed determination of the contribution of these proteins to mycobacterial entry into human neutrophils. The significantly increased number of intracellularly located bacilli of the overproducing M. tuberculosis mutant strains compared with those of "wild-type" M. tuberculosis and the binding interaction of AtsG, GlmU and SahH proteins with human IL-8 may indicate that these proteins participate in the modulation of the early events of infection with tubercle bacilli and could affect pathogen attachment to target cells. PMID- 26829650 TI - Enhanced poly(L-malic acid) production from pretreated cane molasses by Aureobasidium pullulans in fed-batch fermentation. AB - Poly(L-malic acid) (PMA) is a natural polyester with many attractive properties for biomedical application. However, the cost of PMA production is high when glucose is used as a carbon source. To solve this problem, cane molasses as a low cost feedstock was applied for the production of PMA. Six pretreatment methods were applied to cane molasses before fermentation. Pretreatment with combined tricalcium phosphate, potassium ferrocyanide, and sulfuric acid (TPFSA) removed significant amounts of metal ions from cane molasses. The PMA concentration increased from 5.4 g/L (untreated molasses) to 36.9 g/L (TPFSA-pretreated molasses) after fermentation in shake flasks. A fed-batch fermentation strategy was then developed. In this method, TPFSA-pretreated cane molasses solution was continuously fed into the fermentor to maintain the total sugar concentration at 20 g/L. This technique generated approximately 95.4 g/L PMA with a productivity of 0.57 g/L/hr. The present study indicated that fed-batch fermentation using pretreated cane molasses is a feasible technique for producing high amounts of PMA. PMID- 26829649 TI - Engineering microdeletions and microduplications by targeting segmental duplications with CRISPR. AB - Recurrent, reciprocal genomic disorders resulting from non-allelic homologous recombination (NAHR) between near-identical segmental duplications (SDs) are a major cause of human disease, often producing phenotypically distinct syndromes. The genomic architecture of flanking SDs presents a challenge for modeling these syndromes; however, the capability to efficiently generate reciprocal copy number variants (CNVs) that mimic NAHR would represent a valuable modeling tool. We describe here a CRISPR/Cas9 genome engineering method, single-guide CRISPR/Cas targeting of repetitive elements (SCORE), to model reciprocal genomic disorders and demonstrate its capabilities by generating reciprocal CNVs of 16p11.2 and 15q13.3, including alteration of one copy-equivalent of the SDs that mediate NAHR in vivo. The method is reproducible, and RNA sequencing reliably clusters transcriptional signatures from human subjects with in vivo CNVs and their corresponding in vitro models. This new approach will provide broad applicability for the study of genomic disorders and, with further development, may also permit efficient correction of these defects. PMID- 26829651 TI - Identification of gymnodimine D and presence of gymnodimine variants in the dinoflagellate Alexandrium ostenfeldii from the Baltic Sea. AB - Gymnodimines are lipophilic toxins produced by the marine dinoflagellates Karenia selliformis and Alexandrium ostenfeldii. Currently four gymnodimine analogues are known and characterized. Here we describe a novel gymnodimine and a range of gymnodimine related compounds found in an A. ostenfeldii isolate from the northern Baltic Sea. Gymnodimine D (1) was extracted and purified from clonal cultures, and characterized by liquid chromatography-tandem mass spectrometry (LC MS/MS), nuclear magnetic resonance (NMR) spectroscopy, and liquid chromatography high resolution mass spectrometry (LC-HRMS) experiments. The structure of 1 is related to known gymnodimines (2-5) with a six-membered cyclic imine ring and several other fragments typical of gymnodimines. However, the carbon chain in the gymnodimine macrocyclic ring differs from the known gymnodimines in having two tetrahydrofuran rings in the macrocyclic ring. PMID- 26829652 TI - Human scFv antibodies (Afribumabs) against Africanized bee venom: Advances in melittin recognition. AB - Africanized Apis mellifera bees, also known as killer bees, have an exceptional defensive instinct, characterized by mass attacks that may cause envenomation or death. From the years 2000-2013, 77,066 bee accidents occurred in Brazil. Bee venom comprises several substances, including melittin and phospholipase A2 (PLA2). Due to the lack of antivenom for bee envenomation, this study aimed to produce human monoclonal antibody fragments (single chain fragment variable; scFv), by using phage display technology. These fragments targeted melittin and PLA2, the two major components of bee venom, to minimize their toxic effects in cases of mass envenomation. Two phage antibody selections were performed using purified melittin. As the commercial melittin is contaminated with PLA2, phages specific to PLA2 were also obtained during one of the selections. Specific clones for melittin and PLA2 were selected for the production of soluble scFvs, named here Afribumabs: prefix: afrib- (from Africanized bee); stem/suffix: -umab (fully human antibody). Afribumabs 1 and 2 were tested in in vitro and in vivo assays to assess their ability to inhibit the toxic actions of purified melittin, PLA2, and crude bee venom. Afribumabs reduced hemolysis caused by purified melittin and PLA2 and by crude venom in vitro and reduced edema formation in the paws of mice and prolonged the survival of venom-injected animals in vivo. These results demonstrate that Afribumabs may contribute to the production of the first non heterologous antivenom treatment against bee envenomation. Such a treatment may overcome some of the difficulties associated with conventional immunotherapy techniques. PMID- 26829653 TI - Efficient simultaneous adsorption-biodegradation of high-concentrated N,N dimethylformamide from water by Paracoccus denitrificans-graphene oxide microcomposites. AB - Water contamination becomes one of the most pervasive environmental issues all over the world in recent years. In this paper, the functionalization of graphene oxide (GO) with copolymers containing methacrylic acid (MAA) and butyl methacrylate (BMA) was investigated to prepare a new microcomposite material (PGO) via free radical solution polymerization. PGO was used for the adsorption of N,N-dimethylformamide (DMF) from aqueous solution by utilizing the characteristics of ultralarge surface and the Van der Waals force between DMF molecules and polymers on the surface of PGO. Besides, PGO was used not only a high-capable adsorbent but also a carrier for the immobilization of Paracoccus denitrificans cells in the treatment of high-concentrated DMF. Bacterial cells could immobilized on the PGO (PGO@P. denitrificans) stably by covalent coupling process after acclimatization and high-concentrated DMF (2000 mg/L) could be removed completely and relatively rapidly from aqueous solutions by the simultaneous adsorption-biodegradation (SAB) process of PGO@P. denitrificans. Furthermore, the excellent recycle performance of PGO@P. denitrificans made the whole process more economical and practical. PMID- 26829654 TI - Health, coping and subjective well-being: results of a longitudinal study of elderly Israelis. AB - OBJECTIVES: The aim of this study was to test a conceptual model designed to promote the understanding of factors influencing subjective well-being (SWB) in old age. Within this framework, we evaluated the relative influences on elderly Israelis' SWB of health and/or function, personal resources, coping behaviors (reactive and proactive), and changes in all of these factors over time. METHOD: At baseline, 1216 randomly selected elderly persons (75+) were interviewed at home (T1) and 1019 one year later (T2). The conceptual model was evaluated by Structural Equation Modeling (SEM) analysis using AMOS 18. RESULTS: After one year, a relatively high percentage of participants reported decline in health/function (DHF) and in personal resources. The effects of the study variables on T2-SWB were evaluated by a SEM analysis, resulting in a satisfying fit: chi2 = 279.5 (df = 102), p < .001, CFI = .970, NFI = .954, TLI = .955, RMSEA = .046. In addition to significant direct effects of health/function on T2-SWB, health/function was found to indirectly influence T2-SWB. Our analysis showed that health/function had a negative influence on the positive effects of personal resources (function self-efficacy, social support) and the diverse effects of the coping patterns (goal-reengagement - positive; expectations for future care needs - negative; having concrete plans for future care - positive). CONCLUSION: Personal resources and use of appropriate coping behaviors enable elderly people to control their well-being even in the presence of DHF. Evidence-based interventions can help older people to acquire and/or strengthen effective personal resources and coping patterns, thus, promoting their SWB. PMID- 26829655 TI - Maladaptive emotion regulation strategies and stress sensitivity mediate the relation between adverse life events and attenuated positive psychotic symptoms. AB - INTRODUCTION: There is now solid evidence for a relation between adverse life events (ALE) and psychotic symptoms in patients with psychosis and in the general population. A recent study has shown that this relation may be partially mediated by stress sensitivity, suggesting the influence of other factors. The aim of this study was to assess the mediation effect of emotion regulation strategies and stress sensitivity in the relation between ALE and attenuated positive psychotic symptoms (APPS) in the general population. METHODS: Hundred and twelve healthy volunteers were evaluated with measures of APPS, emotion regulation strategies, ALE and stress sensitivity. RESULTS: Results demonstrated that the relation between ALE, hallucination and delusion proneness was completely mediated by maladaptive emotion regulation strategies, but not by stress sensitivity. However, in addition to maladaptive emotion regulation strategies, stress sensitivity demonstrated a mediation effect between ALE and attenuated positive psychotic positive symptoms when positive psychotic symptoms were grouped together. CONCLUSIONS: There are probably several possible trajectories leading to the formation of positive psychotic symptoms and the results of the present study reveal that one such trajectory may involve the maladaptive regulation of negative emotions alongside a certain general vulnerability after experiencing ALE. PMID- 26829656 TI - Morusin Induces TRAIL Sensitization by Regulating EGFR and DR5 in Human Glioblastoma Cells. AB - Glioblastoma is one of the most malignant primary tumors, and the prognosis for glioblastoma patients remains poor. Tumor-necrosis-factor-related apoptosis inducing ligand (TRAIL) is considered a promising anticancer agent due to its remarkable ability to selectively kill tumor cells. However, since many cancers are resistant to TRAIL, strategies to overcome resistance are required for the successful use of TRAIL in the clinic. In the present study, the potential of morusin as a TRAIL sensitizer in human glioblastoma cells was evaluated. Treatment with TRAIL or morusin alone showed weak cytotoxicity in human glioblastoma cells. However, combination treatment of TRAIL with morusin synergistically decreased cell viability and increased apoptosis compared with single treatment. Morusin induced expression of death receptor 5 (DR5), but not DR4 or decoy receptors (DcR1 and DcR2). Furthermore, morusin significantly decreased anti-apoptotic molecules survivin and XIAP. In addition, morusin reduced expression of EGFR and PDFGR as well as phosphorylation of STAT3, possibly mediating down-regulation of survivin and XIAP. Together these results suggest that morusin enhances TRAIL sensitivity in human glioblastoma cells through regulating expression of DR5 and EGFR. Therefore, the combination treatment of TRAIL and morusin may be a new therapeutic strategy for malignant glioma patients. PMID- 26829657 TI - Doping Doctors: The Influence of the Marketing Departments of Pharmaceutical Companies on Physician and Researcher Behavior in Japan. PMID- 26829658 TI - Correction to "Sulfur-Mediated Allylic C-H Alkylation of Tri- and Disubstituted Olefins". PMID- 26829659 TI - Colloid Mobilization in a Fractured Soil: Effect of Pore-Water Exchange between Preferential Flow Paths and Soil Matrix. AB - Exchange of water and solutes between contaminated soil matrix and bulk solution in preferential flow paths has been shown to contribute to the long-term release of dissolved contaminants in the subsurface, but whether and how this exchange can affect the release of colloids in a soil are unclear. To examine this, we applied rainfall solutions of different ionic strength on an intact soil core and compared the resulting changes in effluent colloid concentration through multiple sampling ports. The exchange of water between soil matrix and the preferential flow paths leading to each port was characterized on the basis of the bromide (conservative tracer) breakthrough time at the port. At individual ports, two rainfalls of a certain ionic strength mobilized different amounts of colloids when the soil was pre-exposed to a solution of lower or higher ionic strength. This result indicates that colloid mobilization depended on rainfall solution history, which is referred as colloid mobilization hysteresis. The extent of hysteresis was increased with increases in exchange of pore water and solutes between preferential flow paths and matrix. The results indicate that the soil matrix exchanged the old water from the previous infiltration with new infiltrating water during successive infiltration and changed the pore water chemistry in the preferential flow paths, which in turn affected the release of soil colloids. Therefore, rainfall solution history and soil heterogeneity must be considered to assess colloid mobilization in the subsurface. These findings have implications for the release of colloids, colloid-associated contaminants, and pathogens from soils. PMID- 26829660 TI - Isolated Hepatitis B Core Antibody is Associated With Advanced Hepatic Fibrosis in HIV/HCV Infection But Not in HIV Infection Alone. PMID- 26829661 TI - Brief Report: A Randomized, Double-Blind Comparison of Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate, Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine for Initial HIV-1 Treatment: Week 96 Results. AB - In 2 double-blinded Phase 3 trials, 1733 antiretroviral-naive participants were randomized to tenofovir alafenamide (TAF), a tenofovir prodrug versus tenofovir disoproxil fumarate (TDF), each coformulated with elvitegravir/cobicistat/emtricitabine (E/C/F). At 96 weeks, 86.6% in the TAF arm and 85.2% in the TDF arm had HIV-1 RNA <50 c/mL [difference 1.5%; (95% CI: -1.8% to 4.8%)]. With TAF, there are smaller declines in bone mineral density and more favorable changes in proteinuria, albuminuria, and tubular proteinuria, and no cases of proximal tubulopathy compared with 2 for TDF. These longer-term data support E/C/F/TAF as a safe, well-tolerated, and durable regimen for initial HIV 1 treatment. PMID- 26829662 TI - Adherence to guideline-recommended process measures for squamous cell carcinoma of the head and neck in Ontario: Impact of surgeon and hospital volume. AB - BACKGROUND: The purpose of this study was to measure adherence rates to guideline recommended process measures in patients with head and neck cancer. METHODS: A total of 5720 patients who underwent surgery for head and neck cancer in Ontario between 1993 and 2010 were identified from administrative databases. Adherence to 4 guideline-recommended processes of care was measured and stratified by hospital and physician case volume. RESULTS: Seventy-two percent of patients received preoperative head and neck imaging, 83% received preoperative chest imaging, 58% received preoperative multidisciplinary consultation, and 77% had appropriate follow-up visits. Higher surgeon and hospital surgical volumes were associated with higher adherence rates. CONCLUSION: Adherence rates to guideline-recommended processes of care in the surgical management of patients with head and neck cancer in Ontario were moderate and should be improved. Although adherence rates seem proportional to surgical volume, even the highest volume centers have room to improve. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1987-E1992, 2016. PMID- 26829663 TI - Seedling stage low temperature response in tolerant and susceptible rice genotypes suggests role of relative water content and members of OsSNAC gene family. AB - Low temperature (LT) severely affects rice growth and grain yield. Recently, we reported contrasting genotypes including ARR 09 and Takyer for seedling stage long duration low temperature response. Here we show that susceptible rice genotypes show an increase in lipid peroxide levels and decrease in relative water content (RWC) to a higher extent in comparison to tolerant genotypes in response to 3 h LT. Stress induced NAC family members (OsNAC1, OsNAC2, OsNAC3, and OsNAC5) showed a higher transcript accumulation in tolerant genotypes than in sensitive genotypes after LT treatment suggesting stress tolerance might be due to higher expression of stress-responsive transcription factors. Furthermore, ARR 09 can be used as an important genetic resource to better understand LT tolerance mechanism. PMID- 26829664 TI - Molecular disassembly of rice and lotus starches during thermal processing and its effect on starch digestibility. AB - The molecular disassembly of starch during thermal processing is a major determinant for the susceptibility of starch to enzymatic digestion. In the present study, the effects of thermal processing on the disassembly of the granular structure and the in vitro enzymatic digestibility of rice and lotus starches were investigated. After heating at 50 degrees C, rice and lotus starches did not show significant changes in granular morphology, long-range crystallinity and short-range molecular order. As the temperature increased to 60 degrees C, rice starch underwent a partial gelatinization followed by an incomplete disruption of granular morphology, crystallites and molecular order. In contrast, lotus starch was almost completely gelatinized at 60 degrees C. At 70 degrees C or higher, both starches were fully gelatinized with complete disruption of the micro and macro structures. Our results show that gelatinization greatly increased the in vitro enzymatic digestibility of both starches, but that the degree of disassembly of the starch structure during thermal processing was not a major determinant of the digestibility of gelatinized starch. PMID- 26829665 TI - Best practices for scholarly authors in the age of predatory journals. AB - 'Continuous effort, not strength or intelligence, is the key to understanding our potential.' Margaret J Wheatley. The focus of any academic or research author is to share his or her findings, and to gain respect and reward for publishing. The ideal journal is one that not only publishes an article quickly but also helps the author to improve the article before publication through peer review, selects only the best research so that the author's article lies alongside other high quality articles, and provides maximum (and long-term) visibility and access to the article. Unfortunately, in the real world, authors need to make tradeoffs between high quality journals, those that work quickly, those that are willing to accept the article and those that provide the best access. Into this mix has come the potential of open access as a means of increasing visibility: journals publish the article without a subscription barrier so anyone, anywhere, can read the article. However, the growth of open access (pushed by institutions, grant bodies and governments as a means of improving human health and knowledge) has come with some unforeseen consequences. In this article, Jeffrey Beall discusses one recent phenomenon that has arisen from the open access movement: that of 'predatory publishers'. These are individuals or companies that use the open access financial system (author pays, rather than library subscribes) to defraud authors and readers by promising reputable publishing platforms but delivering nothing of the sort. They frequently have imaginary editorial boards, do not operate any peer review or quality control, are unclear about payment requirements and opaque about ownership or location, include plagiarised content and publish whatever somebody will pay them to publish. Predatory publishers generally make false promises to authors and behave unethically. They also undermine the scholarly information and publishing environment with a deluge of poor quality, unchecked and invalidated articles often published on temporary sites, thus losing the scholarly record. Jeffrey Beall, a librarian in Denver, US, has watched the rise of such fraudulent practice, and manages a blog site that names publishers and journals that he has identified as predatory. While Beall's lists can provide librarians and knowledgeable authors with information on which journals and publishers to be cautious about, several legitimate publishers, library groups and others have joined forces to educate and inform authors in what to look for when selecting journals to publish in (or read). This initiative, called Think. Check. Submit. (http://thinkchecksubmit.org/), was launched in the latter half of 2015 and hopes to raise awareness of disreputable journals while clearly separating them from valid, high quality, open access journals (of which there are many). PIPPA SMART Guest Editor. PMID- 26829666 TI - Decision making on timing of surgery for hip fracture patients on clopidogrel. AB - Patients taking clopidogrel who sustain a fractured neck of femur pose a challenge to orthopaedic surgeons. The aim of this study was to determine whether delay to theatre for these patients affects drop in haemoglobin levels, need for blood transfusion, length of hospital stay and 30-day mortality. A retrospective review of all neck of femur patients admitted at two centres in the North East of England over 3 years revealed 85 patients. Patients were divided into two groups depending on whether they were taking clopidogrel alone (C) or with aspirin (CA). Haemoglobin drop was significantly different in the CA group that was operated on early (CA1) versus the group for which surgery was delayed by over 48 hours (CA2): 3.3g/dl and 1.9g/dl respectively (p=0.01). The mean inpatient stay in group C was 35.9 days while in group CA it was 19.9 days (p=0.002). The mean length of stay in group CA2 (26.7 days) was significantly longer than for CA1 patients (14.1 days) (p=0.01). There were no significant differences in mortality or wound complications. Hip fracture patients on clopidogrel can be safely operated on early provided they are medically stable. Bleeding risk should be borne in mind in those patients on dual therapy with aspirin. PMID- 26829667 TI - Assessment of penetration of dorsal screws after fixation of the distal radius using ultrasound: cadaveric study. AB - INTRODUCTION: Volar locking plates are used to treat unstable and displaced fractures of the distal radius. Potential advantages of stable anatomical reduction (eg early mobilisation) can be limited by penetration of dorsal screws, leading to synovitis and potential rupture of extensor tendons. Despite intraoperative imaging, penetration of dorsal screws continues to be a problem in volar plating of the distal radius. Ultrasound is a well recognised, readily available, diagnostic tool used to assess soft-tissue impingement by orthopaedic hardware. In this cadaveric study, we wished to ascertain the sensitivity and specificity of ultrasound for identification of protrusion of dorsal screws after volar plating of the distal radius. METHODS: Four adult, unpaired phenol-embalmed cadaveric distal radii were used. A VariAxTM Distal Radius Volar Locking Plate system (Stryker, Kalamazoo, MI, USA) was employed for instrumented fixation. A portable SIUI CTS 900 ultrasound machine (Providian Medical, Eastlake, OH, USA) was used to image the dorsal cortex to ascertain screw penetration. RESULTS: Specificity and sensitivity of ultrasound for detection of screw protrusion through the dorsal cortex was 100%. CONCLUSIONS: Ultrasound was found to be a safe and accurate method for assessment of dorsal-screw penetration through the dorsal cortex of the radius after volar plating of the distal radius. It also aids diagnosis of associated tendon disorders (eg tenosynovitis) that might cause pain and limit wrist function. PMID- 26829668 TI - Day surgery for achalasia cardia: Time for consensus? AB - INTRODUCTION: Laparoscopic Heller's myotomy (LHM) is the most effective therapy for achalasia of the oesophagus. Most case series of LHM report a length of hospital stay (LOS) >1 day. We present 14 years of experience of LHM to examine the safety and feasibility of LHM as a day case procedure. METHODS: We retrospectively examined patients undergoing elective LHM for achalasia at our institution between 2000 and 2014. Demographics, episode statistics, prior investigations and interventions were collated. Outcomes, including LOS, complications and re-interventions, were compared for the periods before and after a consensus decision at our institution in 2008 to perform LHM as a day case procedure. RESULTS: Sixty patients with a mean age of 41 +/- 13 years were included, of whom 58% were male. The median LOS for all patients was 1 day (interquartile range [IQR] 0-2.25). Overall, LHM was performed as a day case in 27 (45%) cases, at 2/26 (7.7%) in the first period versus 25/34 (73.5%) in the second (p<0.01). There were no significant differences in age, gender or previous interventions between day surgery and non-day surgery groups. One patient required subsequent unplanned surgery, while six (10%) needed endoscopic treatment of recurrent symptoms within 12 months. CONCLUSIONS: LHM can be performed safely as a day case procedure. Complication rates are low, with only a small proportion of patients requiring endoscopic treatment for symptom recurrence within 1 year. PMID- 26829669 TI - Fresh osteochondral allograft with soft tissue reconstruction for open knee trauma: A 20-year follow-up. PMID- 26829670 TI - External signals shape the epigenome. AB - A new study shows how a single cytokine, interleukin-4, regulates hematopoietic lineage choice by activating the JAK3-STAT6 pathway, which causes dendritic-cell specific DNA demethylation. PMID- 26829671 TI - Graphene oxide-SiO2 hybrid nanostructure as coating material for capillary electrochromatography. AB - Graphene oxide (GO) has been considered as a promising stationary phase for chromatographic separation. However, the very strong adsorption of the analytes on the GO surface lead to the severe peak tailing, which in turn resulting in decreased separation performance. In this work, GO and silica nanoparticles hybrid nanostructures (GO/SiO2 NPs@column) were coated onto the capillary inner wall by passing the mixture of GO and silica sol through the capillary column. The successful of coating of GO/SiO2 NPs onto the capillary wall was confirmed by SEM and electroosmotic flow mobilities test. By partially covering the GO surface with silica nanoparticles, the peak tailing was decreased greatly while the unique high shape selectivity arises from the surface of remained GO was kept. Consequently, compared with the column modified with GO (GO@column), the column modified with GO and silica nanoparticles through layer-by-layer method (GO-SiO2 NPs@column), or the column modified with silica nanoparticles (SiO2 NPs@column), GO/SiO2 NPs@column possessed highest resolutions. The GO/SiO2 NPs@column was applied to separate egg white and both acidic and basic proteins as well as three glycoisoforms of ovalbumin were separated in a single run within 36 min. The intra-day, inter-day, and column-to-column reproducibilities were evaluated by calculating the RSDs of the retention of naphthalene and biphenyl in open-tubular capillary electrochromatography. The RSD values were found to be less than 7.1%. PMID- 26829672 TI - Analysis of the ecological conservation behavior of farmers in payment for ecosystem service programs in eco-environmentally fragile areas using social psychology models. AB - Studies on the ecological conservation behavior of farmers usually focus on individual and socio-economic characteristics without consideration of the underlying psychological constructs, such as farmers' intention and perceptions. This study uses the theory of planned behavior (TPB), a typical social psychology construct, to analyze the factors affecting the intention and behavior of farmers for conserving the ecological achievements from payment for ecosystem service (PES) programs in eco-environmentally fragile areas. Questionnaires based on TPB were administered to 1004 farmers from the Grain to Green Program area in the Loess Plateau, China, with the resulting dataset used to identify the underlying factors determining farmers' intention and behavior based on the structural equation model. The results show that the farmers' intention and behavior toward conserving ecological achievements were explained well by TPB. The farmers'behavior was significantly positively affected by their intention toward conserving ecological achievements, and their intention was significantly influenced by their attitude (positive or negative value of performance), the subjective norm (social pressure in engaging behavior), and perceived behavioral control (perceptions of their ability). The farmers' degree of support for PES programs and their recognition of environmental effects were the factors that most influenced the farmers' attitude. Pressure from neighbors was the most potent driver of the subjective norm. Meanwhile, perceptions of their ability to perform the behavior were the most potent factors affecting intention and it was mostly driven by the farmers' feelings toward environmental improvement and perceived ability (time and labor) to participate in ecological conservation. The drivers of attitude, subjective norm, and perceived behavioral control can be used by policy makers to direct farmers' intention and behavior toward conserving ecological achievements in fragile eco-environmentally areas through PES programs. Thus, this strategy can improve the sustainability of ecological and environmental restoration programs. PMID- 26829673 TI - Recovery of Dynamics and Function in Spiking Neural Networks with Closed-Loop Control. AB - There is a growing interest in developing novel brain stimulation methods to control disease-related aberrant neural activity and to address basic neuroscience questions. Conventional methods for manipulating brain activity rely on open-loop approaches that usually lead to excessive stimulation and, crucially, do not restore the original computations performed by the network. Thus, they are often accompanied by undesired side-effects. Here, we introduce delayed feedback control (DFC), a conceptually simple but effective method, to control pathological oscillations in spiking neural networks (SNNs). Using mathematical analysis and numerical simulations we show that DFC can restore a wide range of aberrant network dynamics either by suppressing or enhancing synchronous irregular activity. Importantly, DFC, besides steering the system back to a healthy state, also recovers the computations performed by the underlying network. Finally, using our theory we identify the role of single neuron and synapse properties in determining the stability of the closed-loop system. PMID- 26829674 TI - Role of dietary flavonoids in amelioration of sugar induced cataractogenesis. AB - Sugar induced cataractogenesis and visual impairment is more prominent ophthalmic problem in humans suffering from diabetes. Flavonoids have been identified as one of the therapeutically important class of phytochemicals possessing myriad of biological activities. Analyzing the anti-cataract effects of flavonoids from natural sources is an important aspect owing to their bioavailability in variety of dietary sources. In the present study a panel of ten dietary flavonoids like 3, 6-dihydroxy flavone, 3, 7-dihydroxy flavone, chrysin, 3-hydroxy-7-methoxy flavone, apigenin, genistein, baicalein, galangin, Biochanin-A, and diosmin were evaluated for their anti-cataract effects in sugar induced lens model studies. Series of parameters like role of flavonoids in glycation induced lens opacity, protein aggregation measurements, carbonyl group formation: a biochemical marker of glycation reaction, non-tryptophan fluorescence: a marker of formation of advanced glycation end products (AGEs) and assessment of (experimental and in silico) aldose reductase inhibition: a key enzyme of polyol pathway involved in cataractogenesis. The results of the study clearly demonstrated the impressive anti-cataract activity of chrysin followed by significant activity by apigenin, baicalein and genistein. The results of the present study may find applications in formulation of functional foods and neutraceuticals for the management of diabetic cataract. PMID- 26829675 TI - Value of first-trimester serum lipid profile in early prediction of preeclampsia and its severity: A prospective cohort study. AB - STUDY OBJECTIVE: The purpose of this study was to evaluate the association of first-trimester serum lipid profile with preeclampsia (PE) and if so, its association with the severity of the disease. STUDY: Prospective cohort study. PATIENT AND METHODS: A total of 251 pregnant women participated in this study in their first trimester. Maternal blood samples were collected between 4 and 12 weeks of gestation. Fasting serum triglycerides (TGs), total cholesterol (TC), HDL-cholesterol, and low-density lipoprotein cholesterol (LDL-C) were drawn and measured by ELISA. From the cohort, 26 women developed PE (16 mild and 10 severe) and 174 remained normotensive and used as control subjects. RESULTS: There was a significant rise in fasting serum TGs, TC, and LDL-C and a significant decrease in HDL-C in women who developed PE than in those who remained normotensive and more significantly evident in severe preeclamptic cases compared to mild cases of PE (p < 0.05). CONCLUSION: Early pregnancy dyslipidemia, particularly hypertriglyceridemia and hypercholesterolemia, may help in predicting women who later develop PE and may help in prediction of its severity. PMID- 26829676 TI - Minimally Invasive In Situ Cubital Tunnel Decompression. AB - The purpose of this study is to describe a modified technique for a minimally invasive approach to in situ ulnar nerve decompression and to provide long-term follow-up. Thirty-one patients were included. DASH and MHQ scores were measured. Mean postoperative DASH score was 10. Eighty percent of patients achieved a postoperative DASH score under 10. Average postoperative MHQ scores were as follows: overall hand function 89, activities of daily living 93, work 92, pain 7, esthetics 95, and satisfaction 84. There were no postoperative neurological complications. No patient required open decompression or transposition. There were no wound complications. This technique addresses all points of possible compression, results in outcomes similar to those reported in the literature, and results in excellent cosmesis. It is a simple and safe technique that avoids the complexities of endoscopy and transposition and has proven to be successful. PMID- 26829677 TI - Physician liability issues and telemedicine: Part 3 of 3. PMID- 26829678 TI - Laryngitis obscuring an anterior glottic mass. PMID- 26829679 TI - Clival lesion: Atypical osteomyelitis vs. a neoplastic process. PMID- 26829680 TI - Hemangioma. PMID- 26829681 TI - Four cystic parathyroid adenomas in a 71-year-old man. PMID- 26829682 TI - Management of sinonasal undifferentiated carcinoma with intracerebral invasion: Clinical experience at a single institution and review of the literature. AB - Sinonasal undifferentiated carcinoma (SNUC) represents less than 1% of all malignancies. Most of the tumors are diagnosed at an advanced stage, when they have already invaded neighboring tissue structures. We describe the cases of 2 patients with a substantial intracerebral extension of SNUC who were treated at our institution. One was treated with surgery followed by chemoradiotherapy. The other was primarily treated with induction chemotherapy with a combination of docetaxel, cisplatin, and 5-fluorouracil followed by concurrent chemo- and radiotherapy. In view of the rarity of SNUC, no prospective clinical trials have been performed and a gold standard for treatment has not yet been established. Therefore, treatment recommendations are based on level IV evidence. These recommendations are diverse and controversial. In our 2 cases, the patient who was treated with induction chemotherapy had a better outcome. In cases of intracerebral extension, radical surgery is necessary and induction chemotherapy should be considered. PMID- 26829683 TI - Laryngotracheal mucormycosis: Report of a case. AB - Airway mucormycosis is a deadly opportunistic infection that affects immunocompromised persons, particularly diabetics and those undergoing chemotherapy. Although it is typically a pulmonary or sinonasal infection, mucormycosis can affect the larynx and trachea, with devastating results. We report the case of a 46-year-old man with human immunodeficiency virus infection, hepatitis C infection, neurosyphilis, and recently diagnosed Burkitt lymphoma who presented with dysphonia and stridor after receiving one dose of intrathecal chemotherapy. Flexible laryngoscopy detected the presence of fibrinous material that was obstructing nearly the entire glottis. Surgical debridement revealed a firm mucosal attachment; there was little bleeding when it was removed. After debridement, the patient's dyspnea improved only to recur 2 days later. After an awake tracheotomy, laryngoscopy and bronchoscopy identified necrosis extending from the supraglottic area to the carina tracheae. Biopsies demonstrated hyphal architecture consistent with mucormycosis. Despite continued debridements, the fibrinous material reaccumulated. The patient was placed in hospice care; his airway remained patent, but he died from other causes several weeks after presentation. The management of airway mucormycosis is challenging and complex. Fungal airway infections should be considered in the differential diagnosis of an immunosuppressed patient who presents with dyspnea, dysphonia, and vocal fold immobility. Timely diagnosis and management are critical for a successful outcome, although the prognosis is poor if the infection is widespread, even with the best of efforts. PMID- 26829684 TI - Vocal fold immobility after finger sweep self-extrusion of impacted food in a choking victim with resolution following laryngeal mask ventilation. AB - We report a case of unilateral vocal fold immobility in a 57-year-old woman that occurred subsequent to a choking episode, which she resolved by removing impacted food with a finger sweep. Other than the unilateral immobility, no abnormality of the laryngeal mucosa or framework was detected on physical examination, laryngoscopy, and computed tomography. Weeks later, the patient underwent an unrelated surgical procedure necessitating laryngeal mask airway ventilation. When she emerged from the procedure, she noted full resolution of her voice symptoms. Office laryngoscopy confirmed the full return of vocal fold function. We discuss possible explanations for the return of function in the context of this unusual onset and resolution. We also review the literature regarding unilateral vocal fold immobility, including its etiology, presentation, workup, and treatment. PMID- 26829685 TI - Granular cell (Abrikossoff) tumor in the head and neck: A series of 5 cases. AB - We evaluated a series of 5 patients-3 men and 2 women, aged 39 to 70 years (mean: 54.4)-with a granular cell tumor (GCT) of the head and neck in an effort to better define the clinical presentation, imaging characteristics, and surgical management of this type of tumor. In all cases, the diagnosis was established by pathologic analysis. There were 2 cases of laryngeal GCT and 1 case each of GCT arising in the nostril, hypopharynx, and the tongue base. The clinical findings were variable, depending on the location and extent of each lesion. Four of these patients underwent endoscopic examination, and in 2 cases computed tomography was performed. Treatment included wide surgical excision of the lesion in all cases. Otolaryngologists should be familiar with this unusual tumor. Although an accurate preoperative diagnosis is extremely difficult to make, appropriate therapeutic intervention is associated with a cure rate that is quite high. PMID- 26829687 TI - Retained crossbow bolt after penetrating facial trauma. AB - We present an unusual case of a retained crossbow bolt in the maxillofacial area of a 31-year-old man. While crossbow injuries are rare, this case is of interest because otolaryngologists are often faced with treating retained foreign objects after penetrating facial trauma. These cases are difficult to manage because of the complexity and variety of injuries that can occur during both the initial trauma and the removal. We focus on the management of the bolt's removal and provide a brief discussion of the relevant literature on crossbow injuries to the head and neck. PMID- 26829688 TI - Urbach-Wiethe disease in a young woman: A case report. AB - Urbach-Wiethe disease (lipoid proteinosis) is an autosomal recessive disorder that is characterized by a general thickening of the skin and mucous membranes. We report the case of a 22-year-old woman with lipoid proteinosis who presented with hoarseness, poor dentition, and skin lesions, and we discuss the management of this rare disease. PMID- 26829689 TI - A useful technique for adjusting nasal tip projection in Asian rhinoplasty: Trapezoidal caudal extension cartilage grafting. AB - The purpose of this article is to present our experience with Asian patients in (1) using a trapezoidal caudal extension cartilage graft to adjust the tip projection in tip refinement for augmentation rhinoplasty, especially for the correction of short nose, and (2) avoiding complications of augmentation rhinoplasty with alloplastic implants. We conducted a retrospective chart review of 358 rhinoplasties that were performed by the corresponding author from January 2004 through July 2009. Patients were included in this study if they had undergone open rhinoplasty with a trapezoidal caudal extension cartilage graft as the only tip-modifying procedure. Patients in whom any additional grafting was performed that might have altered the nasal tip position were excluded. The surgical results were analyzed in terms of the degree of satisfaction judged separately by investigators and by patients. A total of 84 patients-46 males and 38 females, all Asians, aged 13 to 61 years (mean: 29.3)-met our eligibility criteria. Postoperative follow-up for 24 months was achieved in 62 patients. At the 24-month follow-up, the surgeons judged the results to be good or very good in 57 of the 62 patients (91.9%); at the same time, 56 patients (90.3%) said they were satisfied or very satisfied with their aesthetic outcome. Good nasal tip projection, a natural columellar appearance, and improvement in the nasolabial angle were achieved for most patients. Two patients required revision rhinoplasty to correct an insufficient augmentation and migration of the onlay graft. No severe complications were observed during the 2-year follow-up. We have found that trapezoidal caudal extension cartilage grafting in nasal tip refinement is an easy technique to learn and execute, its results are predictable, and it has been associated with no major complications. We recommend trapezoidal caudal extension cartilage grafting for Asian patients as a good and reliable alternative for managing tip projection and support. PMID- 26829690 TI - A study of language development and affecting factors in children aged 5 to 27 months. AB - We conducted a study to assess the factors that affect language development in infants and toddlers using data obtained during developmental screening. Our study group consisted of 505 children-244 (48.3%) boys and 261 (51.7%) girls, aged 5 to 27 months. The children were divided into four age groups: group 1, which we designated as the "6 months" group (age range: 5 to 7 mo); group 2, designated as the "12 months" group (11 to 13 mo); group 3, designated as the "18 months" group (17 to 19 mo); and group 4, designated as the "24 months" group (23 to 27 mo). In addition to demographic data, we compiled data using the Denver II Developmental Screening Test, as well as neurologic examination findings and medical histories. At 6 months, the social item "Works for toy out of reach" was positively related to all language development items. Two gross motor development items-"Pull to sit, no head lag" and "Lifts chest with arm support"-were related to the "Turns to sound" and "Turns to voice" items, respectively. Overall, children whose mothers had higher education levels and who were living in higher socioeconomic areas showed significantly greater language development, as did boys, specifically. At 12 months, higher maternal ages, some gross motor development items, and some social items were related to better language development, and children living in higher socioeconomic areas had a significantly increased ability to pass the "4 words other than mama/dada" item. At 18 months, the ability of girls to pass the "4 words other than mama/dada" item increased, and children who passed the "4 words other than mama/dada" item did not pass the "Throws ball" gross motor item. At 24 months, children whose mothers were older had better "Combines 2 words" and "Speech half intelligible" items, girls had better "Comprehends prepositions (such as under/above)" skills, and boys had better "Shows 4 parts of doll" skills. We conclude that language items appear to change together with gross motor items and social development, and that they can be influenced by a family's socioeconomic level. However, as children get older, language development diverges from gross motor development. PMID- 26829691 TI - Intratonsillar metastasis of EBV-positive nasopharyngeal carcinoma. AB - We present the case of a 47-year-old man with a history of Epstein-Barr-virus positive nasopharyngeal carcino- ma who developed a metastasis to the palatine tonsil. To the best of our knowledge, this is the first reported case of an intratonsillar metastasis of a nasopharyngeal carcinoma. The aim of this report is to emphasize the importance of vigilant surveillance in patients with nasopharyngeal carcinoma. This case also demonstrates that an atypical metastatic pattern can raise suspicion of a local disease recurrence. PMID- 26829692 TI - Case series: Internal jugular vein ectasia in pediatric patients. AB - Jugular vein ectasia is a dilation of the vein without tortuosity. This finding can easily be misdiagnosed or overlooked. Because of its rarity, many pediatricians, otolaryngologists, and pediatric surgeons are unfamiliar with this diagnosis and how to manage it. We report a series of 2 cases of internal jugular vein ectasia in pediatric patients and discuss its clinical findings, simple and noninvasive method of diagnosis, and treatment. PMID- 26829693 TI - Management of a cocaine-induced palatal perforation with a nasal septal button. AB - A cocaine-induced midline destructive lesion (CIMDL) is a rare consequence of cocaine insufflation that involves the nose, sinuses, and occasionally the palate. Palatal perforations compromise swallowing, mastication, and speech. An obturator prosthesis can be used to overcome these complications. In selected cases, a nasal septal button is a good alternative for the sealing of a palatal perforation, especially when surgery is not indicated, such as in cases of persistent cocaine abuse. Abstinence from cocaine is the most effective long-term management option for patients with a CIMDL, and surgical correction of the defect should be postponed until the patient stops sniffing cocaine and the lesion becomes stable. We describe the case of a 39-year-old cocaine abuser whose oronasal communication was plugged with a nasal septal button, which resulted in an immediate alleviation of his oronasal reflux. PMID- 26829694 TI - Slag injury to the tympanic membrane. PMID- 26829695 TI - Pneumatization of all three nasal turbinates. PMID- 26829696 TI - Congenital choristoma (hairy polyp) of the eustachian tube: Surgical management of a rare clinical entity. PMID- 26829697 TI - A case of lipoma arising in the eustachian tube. AB - We report a case of a lipoma inside the eustachian tube, an extremely rare location for this lesion. To the best of our knowledge, this is only the second such case that has been described in the literature. The patient was a 47-year old man, a fighter pilot, who was referred to our hospital with a 3-year history of (1) fullness in the right ear secondary to recurrent serous otitis media and (2) right ear pain, which was especially acute during flights. Nasopharyngeal endoscopy, computed tomography, and magnetic resonance imaging detected the presence of a well-encapsulated lesion inside the eustachian tube; macroscopic and radiologic findings identified the mass as a lipoma. The lesion was completely removed via transnasal endoscopy. Histopathologic evaluation confirmed the diagnosis of lipoma. The patient's postoperative course was favorable, and he was able to fly again without any ear complaints. Radiologic examination is useful for the diagnosis and preoperative evaluation of this benign tumor. Lesions located in the lower part of the eustachian tube can be easily removed via a transnasal endoscopic approach. PMID- 26829699 TI - ERRATA. PMID- 26829698 TI - Huge lipoma of the right parotid gland: Case report and review of 42 cases. AB - Lipomas are rarely found in the parotid gland region. Because of their rarity at this site, they are not often considered in the differential diagnosis of parotid tumors. The parotid lipoma is a slowly growing, asymptomatic, freely movable, soft mass. Preoperative diagnosis is generally difficult. We present a case of a slowly enlarging mass of the parotid region in a 44-year-old man that proved to be a lipomatous tumor of the parotid gland. We also review 42 other cases from the literature. Our patient's huge tumor was located in the superficial lobe of the gland, and a parotidectomy with preservation of the facial nerve was performed. There was no complication or recurrence of the tumor after a follow-up of 1 year. PMID- 26829700 TI - Changes in atropine use for out-of-hospital cardiac arrest patients with non shockable rhythm between 2002 and 2012. PMID- 26829701 TI - Can serial focussed echocardiographic evaluation in life support (FEEL) predict resuscitation outcome or termination of resuscitation (TOR)? A pilot study. AB - AIM OF THE STUDY: This study aimed to evaluate the correlation between serial echocardiography findings and return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA) and to examine whether echocardiographic cardiac standstill duration can be used to predict ROSC. METHODS: This was a prospective observational study of non-consecutive non-trauma adult patients with OHCA. Echocardiography was performed every 2 min during a pulse check for <10s throughout the resuscitation effort managed according to advanced life support treatment guidelines. Echocardiography findings were recorded as video clips. RESULTS: Forty-eight patients were enrolled in the study. Serial echocardiographic cardiac standstill duration in the ROSC and no ROSC groups were 2.86 +/- 2.07 min versus 20.30 +/- 8.42 min, respectively (p<0.001). Cardiac standstill duration >=10 min predicted non-ROSC with a sensitivity of 90.0%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 93.3%. A receiver operating characteristic curve was generated to determine the accuracy of serial echocardiographic cardiac standstill duration for predicting no ROSC. The area under the curve was 0.991 (p<0.000). CONCLUSIONS: In all patients with serial echocardiographic cardiac standstill >=10 min, no patients had ROSC. These results displayed compelling test performance and discrimination ability for subjects with and without ROSC. Our study is suggestive, and it warrants further study. PMID- 26829702 TI - Description of life-threatening events occurring in workplaces and requiring dispatch Advanced Life Support Ambulances in an urban area. PMID- 26829703 TI - Reply to: 'What initial oxygen is best for preterm infants in the delivery room? A response to the 2015 neonatal resuscitation guidelines.'. PMID- 26829704 TI - Valence Band Dependent Charge Transport in Bulk Molecular Electronic Devices Incorporating Highly Conjugated Multi-[(Porphinato)Metal] Oligomers. AB - Molecular electronics offers the potential to control device functions through the fundamental electronic properties of individual molecules, but realization of such possibilities is typically frustrated when such specialized molecules are integrated into a larger area device. Here we utilize highly conjugated (porphinato)metal-based oligomers (PM(n) structures) as molecular wire components of nanotransfer printed (nTP) molecular junctions; electrical characterization of these "bulk" nTP devices highlights device resistances that depend on PM(n) wire length. Device resistance measurements, determined as a function of PM(n) molecular length, were utilized to evaluate the magnitude of a phenomenological beta corresponding to the resistance decay parameter across the barrier; these data show that the magnitude of this beta value is modulated via porphyrin macrocycle central metal atom substitution [beta(PZn(n); 0.065 A(-1)) < beta(PCu(n); 0.132 A(-1)) < beta(PNi(n); 0.176 A(-1))]. Cyclic voltammetric data, and ultraviolet photoelectron spectroscopic studies carried out at gold surfaces, demonstrate that these nTP device resistances track with the valence band energy levels of the PM(n) wire, which were modulated via porphyrin macrocycle central metal atom substitution. This study demonstrates the ability to fabricate "bulk" and scalable electronic devices in which function derives from the electronic properties of discrete single molecules, and underscores how a critical device function--wire resistance--may be straightforwardly engineered by PM(n) molecular composition. PMID- 26829705 TI - Detection of small bowel tumor based on multi-scale curvelet analysis and fractal technology in capsule endoscopy. AB - Wireless capsule endoscopy (WCE) has been a revolutionary technique to noninvasively inspect gastrointestinal (GI) tract diseases, especially small bowel tumor. However, it is a tedious task for physicians to examine captured images. To develop a computer-aid diagnosis tool for relieving the huge burden of physicians, the intestinal video data from 89 clinical patients with the indications of potential tumors was analyzed. Out of the 89 patients, 15(16.8%) were diagnosed with small bowel tumor. A novel set of textural features that integrate multi-scale curvelet and fractal technology were proposed to distinguish normal images from tumor images. The second order textural descriptors as well as higher order moments between different color channels were computed from images synthesized by the inverse curvelet transform of the selected scales. Then, a classification approach based on support vector machine (SVM) and genetic algorithm (GA) was further employed to select the optimal feature set and classify the real small bowel images. Extensive comparison experiments validate that the proposed automatic diagnosis scheme achieves a promising tumor classification performance of 97.8% sensitivity and 96.7% specificity in the selected images from our clinical data. PMID- 26829706 TI - Parallel scheme for real-time detection of photosensitive seizures. AB - The production and distribution of videos and animations on gaming and self authoring websites are booming. However, given this rise in self-authoring, there is increased concern for the health and safety of people who suffer from a neurological disorder called photosensitivity or photosensitive epilepsy. These people can suffer seizures from viewing video with hazardous content. This paper presents a spatiotemporal pattern detection algorithm that can detect hazardous content in streaming video in real time. A tool is developed for producing test videos with hazardous content, and then those test videos are used to evaluate the proposed algorithm, as well as an existing post-processing tool that is currently being used for detecting such patterns. To perform the detection in real time, the proposed algorithm was implemented on a dual core processor, using a pipelined/parallel software architecture. Results indicate that the proposed method provides better detection performance, allowing for the masking of seizure inducing patterns in real time. PMID- 26829707 TI - High-Performance Microchanneled Asymmetric Gd(0.1)Ce(0.9)O(1.95-delta) La(0.6)Sr(0.4)FeO(3-delta)-Based Membranes for Oxygen Separation. AB - A microchanneled asymmetric dual phase composite membrane of 70 vol % Gd(0.1)Ce(0.9)O(1.95-delta)-30 vol % La(0.6)Sr(0.4)FeO(3-delta) (CGO-LSF) was fabricated by a "one step" phase-inversion tape casting. The sample consists of a thin dense membrane (100 MUm) and a porous substrate including "finger-like" microchannels. The oxygen permeation flux through the membrane with and without catalytic surface layers was investigated under a variety of oxygen partial pressure gradients. At 900 degrees C, the oxygen permeation flux of the bare membrane was 1.6 (STP) ml cm(-2) min(-1) for the air/He-case and 10.10 (STP) ml cm(-2) min(-1) for the air/CO-case. Oxygen flux measurements as well as electrical conductivity relaxation show that the oxygen flux through the bare membrane without catalyst is limited by the oxygen surface exchange. The surface exchange can be enhanced by introduction of catalyst on the membrane surface. An increase of the oxygen flux of ~1.49 (STP) mL cm(-2) min(-1) at 900 degrees C was observed when catalyst is added for the air/He-case. Mass transfer polarization through the finger-like support was confirmed to be negligible, which benefits the overall performance. A stable flux of 7.00 (STP) ml cm(-2) min(-1) was observed between air/CO/CO2 over 200 h at 850 degrees C. Partial surface decomposition was observed on the permeate side exposed to CO, in line with predictions from thermodynamic calculations. In a mixture of CO, CO2, H2, and H2O at similar oxygen activity the material will according to the calculation not decompose. The microchanneled asymmetric CGO-LSF membranes show high oxygen permeability and chemical stability under a range of technologically relevant oxygen potential gradients. PMID- 26829708 TI - Interactions and Translational Dynamics of Phosphatidylinositol Bisphosphate (PIP2) Lipids in Asymmetric Lipid Bilayers. AB - Phosphatidylinositol phosphate (PIP) lipids are critical to many cell signaling pathways, in part by acting as molecular beacons that recruit peripheral membrane proteins to specific locations within the plasma membrane. Understanding the biophysics of PIP-protein interactions is critical to developing a chemically detailed model of cell communication. Resolving such interactions is challenging, even in model membrane systems, because of the difficulty in preparing PIP containing membranes with high fluidity and integrity. Here we report on a simple, vesicle-based protocol for preparing asymmetric supported lipid bilayers in which fluorescent PIP lipid analogues are found only on the top leaflet of the supported membrane facing the bulk solution. With this asymmetric distribution of lipids between the leaflets, the fluorescent signal from the PIP lipid analogue reports directly on interactions between the peripheral molecules and the top leaflet of the membrane. Asymmetric PIP-containing bilayers are an ideal platform to investigate the interaction of PIP with peripheral membrane proteins using fluorescence-based imaging approaches. We demonstrate their usefulness here with a combined fluorescence correlation spectroscopy and single particle tracking study of the interaction between PIP2 lipids and a polycationic polymer, quaternized polyvinylpyridine (QPVP). With this approach we are able to quantify the microscopic features of the mobility coupling between PIP2 lipids and polybasic QPVP. With single particle tracking we observe individual PIP2 lipids switch from Brownian to intermittent motion as they become transiently trapped by QPVP. PMID- 26829709 TI - Glucocorticoid mediated regulation of inflammation in human monocytes is associated with depressive mood and obesity. AB - Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is observed in various conditions, including depression and obesity, which are also often related. Glucocorticoid (GC) resistance and desensitization of peripheral GC receptors (GRs) are often the case in HPA dysregulation seen in depression, and GC plays a critical role in regulation of inflammation. Given the growing evidence that inflammation is a central feature of some depression cases and obesity, we aimed to investigate the immune-regulatory role of GC-GR in relation to depressive mood and obesity in 35 healthy men and women. Depressive mood and level of obesity were assessed, using Beck Depression Inventory (BDI-Ia) and body mass index (BMI), respectively. We measured plasma cortisol levels via enzyme linked immunosorbent assay and lipopolysaccharide-stimulated intracellular tumor necrosis factor (TNF) production by monocytes, using flow cytometry. Cortisol sensitivity was determined by the difference in monocytic TNF production between the conditions of 1 and 0 MUM cortisol incubation ("cortisol-mediated inflammation regulation, CoMIR"). GR vs. mineralocorticoid receptor (MR) antagonism for CoMIR was examined by using mifepristone and spironolactone. A series of multiple regression analyses were performed to investigate independent contribution of depressive mood vs. obesity after controlling for age, gender, systolic blood pressure (SBP), and plasma cortisol in predicting CoMIR. CoMIR was explained by somatic subcomponents of depressive mood (BDI-S: beta=-0.499, p=0.001), or BMI (beta=-0.466, p<0.01) in separate models. The effects of BMI disappeared when BDI-S was controlled for in the model, while BDI-S remained a significant independent predictor for CoMIR (beta=-0.369, p<0.05). However, BMI remained the only independent predictor when BDI-T or BDI-C were controlled for in the model. Mediation analyses also revealed that the relationship between BMI and CoMIR was mediated by BDI-S. The exploratory findings of the relative GR vs. MR roles in CoMIR, using GR and MR blockers, indicated that CoMIR in our cellular model was predominantly mediated by GRs at the higher cortisol dose (1 MUM). There was initial indication that greater obesity and somatic depressive symptoms were associated with smaller efficacy of the blockers, which warrants further investigation. Our findings, although in a preclinical sample, signify the shared pathophysiology of immune dysregulation in depression and obesity and warrant further mechanistic investigation. PMID- 26829710 TI - Behavioral and self-reported sensitivity to reward are linked to stress-related differences in positive affect. AB - Despite the high prevalence of stress exposure healthy adaptation or resilience is a common response. Theoretical work and recent empirical evidence suggest that a robust reward system, in part, supports healthy adaptation by preserving positive emotions even under exceptionally stressful circumstances. We tested this prediction by examining empirical relations among behavioral and self reported measures of sensitivity to reward, trait resilience, and measures of affect in the context of experimentally induced stress. Using a quasi experimental design we obtained measures of sensitivity to reward (self-report and behavioral), as well as affective and physiological responses to experimental psychosocial stress in a sample of 140 healthy college-age participants. We used regression-based moderation and mediational models to assess associations among sensitivity to reward, affect in the context of stress, and trait resilience and found that an interaction between exposure to experimental stress and self reported sensitivity to reward predicted positive affect following experimental procedure. Participants with high sensitivity to reward reported higher positive affect following stress. Moreover, positive affect during or after stress mediated the relation between sensitivity to reward and trait resilience. Consistent with the prediction that a robust reward system serves as a protective factor against stress-related negative outcomes, our results found predictive associations among sensitivity to reward, positive affect, and resilience. PMID- 26829711 TI - Chemopreventive Effects of Alpha Lipoic Acid on Obesity-Related Cancers. AB - BACKGROUND: It has been generally accepted that being overweight or obese is a risk factor for several types of cancers, including breast, thyroid, colon, pancreatic and liver. In fact, people who are obese have more fat tissues that can produce hormones, such as insulin or estrogen, which may cause cancer cells to grow. Alpha lipoic acid (ALA) is anorganosulfur compound derived from octanoic acid, which is produced in animals normally, and is essential for aerobic metabolism. SUMMARY: Studies in both in vitro cells and in vivo animal models have shown that ALA inhibits the initiation and promotion stages of carcinogenesis, suggesting that ALA has considerable attention as a chemopreventive agent. This brief review collects the scattered data available in the literature concerning ALA and highlights its anti-cancer properties, intermediary metabolism and exploratory implications. KEY MESSAGES: Based on scientific evidences so far, ALA might be useful agents in the management or chemoprevention of obesity-related cancers. PMID- 26829712 TI - Forebrain-specific loss of synaptic GABAA receptors results in altered neuronal excitability and synaptic plasticity in mice. AB - Mutations that result in the defective trafficking of gamma2 subunit containing GABAA receptors (gamma2-GABAARs) are known to reduce synaptic inhibition. Whether perturbed clustering of non-mutated GABAARs similarly reduces synaptic inhibition in vivo is less clear. In this study we provide evidence that the loss of postsynaptic gamma2-GABAARs upon postnatal ablation of gephyrin, the major scaffolding protein of inhibitory postsynapses, from mature principal neurons within the forebrain results in reduced induction of long-term potentiation (LTP) and impaired network excitability within the hippocampal dentate gyrus. The preferential reduction in not only synaptic gamma2-GABAAR cluster number at dendritic sites but also the decrease in gamma2-GABAAR density within individual clusters at dendritic inhibitory synapses suggests that distal synapses are more sensitive to the loss of gephyrin expression than proximal synapses. The fact that these mice display behavioural features of anxiety and epilepsy emphasises the importance of postsynaptic gamma2-GABAAR clustering for synaptic inhibition. PMID- 26829713 TI - Is Knowledge Regarding Tuberculosis Associated with Stigmatising and Discriminating Attitudes of General Population towards Tuberculosis Patients? Findings from a Community Based Survey in 30 Districts of India. AB - BACKGROUND: Stigmatising and discriminating attitudes may discourage tuberculosis (TB) patients from actively seeking medical care, hide their disease status, and discontinue treatment. It is expected that appropriate knowledge regarding TB should remove stigmatising and discriminating attitudes. In this study we assessed the prevalence of stigmatising and discriminating attitudes towards TB patients among general population and their association with knowledge regarding TB. METHOD: A cross-sectional knowledge, attitude and practice survey was conducted in 30 districts of India in January-March 2011. A total of 4562 respondents from general population were interviewed using semi-structured questionnaires which contained items to measure stigma, discrimination and knowledge on TB. RESULT: Of the 4562 interviewed, 3823 were eligible for the current analysis. Of these, 73% (95% CI 71.4-74.2) had stigmatising and 98% (95% CI 97.4-98.3) had discriminating attitude towards TB patients. Only 17% (95% CI 15.6-18.0) of the respondents had appropriate knowledge regarding TB with even lower levels observed amongst females, rural areas and respondents from low income groups. Surprisingly stigmatising (adjusted OR 1.31 (0.78-2.18) and discriminating (adjusted OR 0.79 (0.43-1.44) attitudes were independent of knowledge regarding TB. CONCLUSION: Stigmatising and discriminating attitudes towards TB patients remain high among the general population in India. Since these attitudes were independent of the knowledge regarding TB, it is possible that the current disseminated knowledge regarding TB which is mainly from a medical perspective may not be adequately addressing the factors that lead to stigma and discrimination towards TB patients. Therefore, there is an urgent need to review the messages and strategies currently used for disseminating knowledge regarding TB among general population and revise them appropriately. The disseminated knowledge should include medical, psycho-social and economic aspects of TB that not only informs people about medical aspects of TB disease, but also removes stigma and discrimination. PMID- 26829714 TI - Convergence in patient-therapist therapeutic alliance ratings and its relation to outcome in chronic depression treatment. AB - OBJECTIVE: This study tested whether discrepancy between patients' and therapists' ratings of the therapeutic alliance, as well as convergence in their alliance ratings over time, predicted outcome in chronic depression treatment. METHOD: Data derived from a controlled trial of partial or non-responders to open label pharmacotherapy subsequently randomized to 12 weeks of algorithm-driven pharmacotherapy alone or pharmacotherapy plus psychotherapy. The current study focused on the psychotherapy conditions (N = 357). Dyadic multilevel modeling was used to assess alliance discrepancy and alliance convergence over time as predictors of two depression measures: one pharmacotherapist-rated (Quick Inventory of Depressive Symptoms-Clinician; QIDS-C), the other blind interviewer rated (Hamilton Rating Scale for Depression; HAMD). RESULTS: Patients' and therapists' alliance ratings became more similar, or convergent, over the course of psychotherapy. Higher alliance convergence was associated with greater reductions in QIDS-C depression across psychotherapy. Alliance convergence was not significantly associated with declines in HAMD depression; however, greater alliance convergence was related to lower HAMD scores at 3-month follow-up. CONCLUSIONS: The results partially support the hypothesis that increasing patient therapist consensus on alliance quality during psychotherapy may improve treatment and longer term outcomes. PMID- 26829715 TI - Inactivation of Mitochondrial Complex I Induces the Expression of a Twin Cysteine Protein that Targets and Affects Cytosolic, Chloroplastidic and Mitochondrial Function. AB - At12Cys-1 (At5g64400) and At12Cys-2 (At5g09570) are two closely related isogenes that encode small, twin cysteine proteins, typically located in mitochondria. At12Cys-2 transcript is induced in a variety of mutants with disrupted mitochondrial proteins, but an increase in At12Cys protein is only detected in mutants with reduced mitochondrial complex I abundance. Induction of At12Cys protein in mutants that lack mitochondrial complex I is accompanied by At12Cys protein located in mitochondria, chloroplasts, and the cytosol. Biochemical analyses revealed that even single gene deletions, i.e., At12cys-1 or At12cys-2, have an effect on mitochondrial and chloroplast functions. However, only double mutants, i.e., At12cys-1:At12cys-2, affect the abundance of protein and mRNA transcripts encoding translation elongation factors as well as rRNA abundance. Blue native PAGE showed that At12Cys co-migrated with mitochondrial supercomplex I + III. Likewise, deletion of both At12cys-1 and At12cys-2 genes, but not single gene deletions, results in enhanced tolerance to drought and light stress and increased anti-oxidant capacity. The induction and multiple localization of At12Cys upon a reduction in complex I abundance provides a mechanism to specifically signal mitochondrial dysfunction to the cytosol and then beyond to other organelles in the cell. PMID- 26829716 TI - Development of an Analysis Pipeline Characterizing Multiple Hypervariable Regions of 16S rRNA Using Mock Samples. AB - OBJECTIVES: There is much speculation on which hypervariable region provides the highest bacterial specificity in 16S rRNA sequencing. The optimum solution to prevent bias and to obtain a comprehensive view of complex bacterial communities would be to sequence the entire 16S rRNA gene; however, this is not possible with second generation standard library design and short-read next-generation sequencing technology. METHODS: This paper examines a new process using seven hypervariable or V regions of the 16S rRNA (six amplicons: V2, V3, V4, V6-7, V8, and V9) processed simultaneously on the Ion Torrent Personal Genome Machine (Life Technologies, Grand Island, NY). Four mock samples were amplified using the 16S Ion Metagenomics KitTM (Life Technologies) and their sequencing data is subjected to a novel analytical pipeline. RESULTS: Results are presented at family and genus level. The Kullback-Leibler divergence (DKL), a measure of the departure of the computed from the nominal bacterial distribution in the mock samples, was used to infer which region performed best at the family and genus levels. Three different hypervariable regions, V2, V4, and V6-7, produced the lowest divergence compared to the known mock sample. The V9 region gave the highest (worst) average DKL while the V4 gave the lowest (best) average DKL. In addition to having a high DKL, the V9 region in both the forward and reverse directions performed the worst finding only 17% and 53% of the known family level and 12% and 47% of the genus level bacteria, while results from the forward and reverse V4 region identified all 17 family level bacteria. CONCLUSIONS: The results of our analysis have shown that our sequencing methods using 6 hypervariable regions of the 16S rRNA and subsequent analysis is valid. This method also allowed for the assessment of how well each of the variable regions might perform simultaneously. Our findings will provide the basis for future work intended to assess microbial abundance at different time points throughout a clinical protocol. PMID- 26829717 TI - Laser Vaporization of the Prostate With the 180-W XPS-Greenlight Laser in Patients With Ongoing Platelet Aggregation Inhibition and Oral Anticoagulation. AB - OBJECTIVE: To characterize the safety and efficacy of the 180-W XPS-Greenlight laser in patients on systemic anticoagulation. MATERIALS AND METHODS: A retrospective analysis of 384 patients who underwent photoselective vaporization of the prostate with the 180-W XPS-laser between 2010 and 2013 at two centers in the United States and Switzerland was performed. The primary outcome was the intraoperative and postoperative complication rates for those on anticoagulation undergoing photoselective vaporization of the prostate. The secondary outcome was International Prostate Symptom Scores, postvoid residual, maximum flow rate, and prostate-specific antigen levels. RESULTS: Of 384 patients, aspirin, clopidogrel, and warfarin were used in 146 (38%), 34 (8.9%), and 57 (14.8%) patients, respectively. Single-drug, two-drug, and three-drug combinations were used in 142 (35.5%), 37 (9.3%), and 7 (1.7%) of the cases. Median lasing time (39 min vs 36 min; P = .99) and number of fibers used (1.0 vs 1.0; P = .63) were comparable between patients on vs off systemic anticoagulation. Postoperatively, urinary symptoms (International Prostate Symptom Score, quality of life) and objective voiding parameters (maximum flow rate, postvoid residual) improved in both groups of patients. During a maximum follow-up of 2 years, patients on vs off systemic anticoagulation did not show any significant differences in the rate of postoperative urinary tract infection (3.8% vs 5.1%; P = .71), retention (5.1% vs 5.9%; P = .71), urethral stricture (1.5% vs none, P = .05), and reoperation (2.2% vs 1.5%; P = .49). The primary limitation is the retrospective nature of the study. CONCLUSION: Photovaporization of the prostate with the 180-W XPS-laser is a safe and effective minimal-invasive treatment option for patients on systemic anticoagulation. PMID- 26829718 TI - Solifenacin and Tamsulosin Combination Therapy Decreases Urine Nerve Growth Factor/Creatinine Levels in Men. AB - OBJECTIVE: To evaluate urinary nerve growth factor (NGF)/creatinine (Cr) levels from men with symptomatic lower urinary tract symptoms (LUTS) and measure the effect of combination therapy with solifenacin and tamsulosin. MATERIALS AND METHODS: From January 2012 to February 2014, all male patients referred for evaluation and management of LUTS were screened for enrollment. In all subjects, urinary NGF and Cr levels were measured and normalized to the urinary Cr concentrations (NGF/Cr). Uroflow, postvoid residual, and symptom questionnaires were measured at baseline, 4 weeks, 8 weeks, and 12 weeks after starting combination therapy with solifenacin 5 mg and tamsulosin 0.4 mg. The primary endpoint was urinary NGF and NGF/Cr change from baseline compared with week 12. RESULTS: Ten patients were recruited into the study. Peak urine flow at baseline 20.3 +/- 2.5 ml/s and postvoid residual 45.3 +/- 13.6 ml did not significantly change with 3 months of combination treatment 14.9 +/- 1.8 ml/s and 58.5 +/- 23.9 ml. However, urine NGF/Cr (pg/mg) levels were significantly reduced following treatment with levels of 39.7 +/- 6.6 at baseline to 17.9 +/- 5.1 at 3 months (P value <.05). The decrease in urine NGF/Cr levels correlated with significant decreases in patient reported outcomes. CONCLUSION: Male patients with LUTS had decreased urinary NGF/Cr levels after treatment with combination solifenacin and tamsulosin in this novel pilot study. This corresponded with improvement in patient reported outcomes. PMID- 26829719 TI - Coccidioidomycosis in infants: A retrospective case series. AB - INTRODUCTION: In contrast to adults, coccidioidomycosis is a rare disease in infants and the mechanisms of disease acquisition are not well described in infants. The purpose of this study was to describe the clinical presentation, treatment, and outcome of pulmonary coccidioidomycosis in infants in an endemic area. METHODS: We performed a retrospective observational study of all patients less than 12 months of age admitted to a tertiary free standing children's hospital from 2003-2012 diagnosed with coccidioidomycosis. RESULTS: Thirteen infants were hospitalized during the study period. The majority of the patients presented with upper and/or lower respiratory tract infection. The most common presenting symptoms included fever (77%), cough (61%), and respiratory distress (38%). Disseminated disease, included pericardial effusion, neck abscess, and lesions in the cerebellum, basal ganglia and left temporoparietal skull. Fluconazole was the initial, antifungal agent used. Amphotericin B was reserved for significant lung disease and disseminated cases. Failed response to fluconazole and amphotericin B were treated with a combination of voriconazole and caspofungin. Average length of treatment was 4 years. All patients survived to hospital discharge. The majority of the patients had resolution of chest radiograph and coccidiodal complement fixing antibody titers. DISCUSSION: Infant coccidioidomycosis has a non-specific presentation and can mimic common infant respiratory illnesses. In endemic areas, coccidioidomycosis should be considered in the differential diagnosis of infants with pulmonary symptoms unresponsive to conventional treatment. Pediatr Pulmonol. 2016;51:858-862. (c) 2016 Wiley Periodicals, Inc. PMID- 26829721 TI - Correction to Real-Time In Situ HRTEM-Resolved Resistance Switching of Ag2S Nanoscale Ionic Conductor. PMID- 26829720 TI - Investigating the Consequences of Interference between Multiple CD8+ T Cell Escape Mutations in Early HIV Infection. AB - During early human immunodeficiency virus (HIV) infection multiple CD8+ T cell responses are elicited almost simultaneously. These responses exert strong selective pressures on different parts of HIV's genome, and select for mutations that escape recognition and are thus beneficial to the virus. Some studies reveal that the later these escape mutations emerge, the more slowly they go to fixation. This pattern of escape rate decrease(ERD) can arise by distinct mechanisms. In particular, in large populations with high beneficial mutation rates interference among different escape strains--an effect that can emerge in evolution with asexual reproduction and results in delayed fixation times of beneficial mutations compared to sexual reproduction--could significantly impact the escape rates of mutations. In this paper, we investigated how interference between these concurrent escape mutations affects their escape rates in systems with multiple epitopes, and whether it could be a source of the ERD pattern. To address these issues, we developed a multilocus Wright-Fisher model of HIV dynamics with selection, mutation and recombination, serving as a null-model for interference. We also derived an interference-free null model assuming initial neutral evolution before immune response elicitation. We found that interference between several equally selectively advantageous mutations can generate the observed ERD pattern. We also found that the number of loci, as well as recombination rates substantially affect ERD. These effects can be explained by the underexponential decline of escape rates over time. Lastly, we found that the observed ERD pattern in HIV infected individuals is consistent with both independent, interference-free mutations as well as interference effects. Our results confirm that interference effects should be considered when analyzing HIV escape mutations. The challenge in estimating escape rates and mutation associated selective coefficients posed by interference effects cannot simply be overcome by improved sampling frequencies or sizes. This problem is a consequence of the fundamental shortcomings of current estimation techniques under interference regimes. Hence, accounting for the stochastic nature of competition between mutations demands novel estimation methodologies based on the analysis of HIV strains, rather than mutation frequencies. PMID- 26829722 TI - [Preimplantation genetic diagnosis for carriers of thalassemia and chromosomal abnormality]. AB - OBJECTIVE: To provide preimplantation genetic diagnosis(PGD) for two couples carrying thalassemia mutations and chromosomal abnormalities. METHODS: Couple 1 were both carriers of beta 41/42 thalassemia mutations, while the husband has carried a reciprocal translocation with a karyotype of 46,XY,inv(9)(p11;q13),t(11;22)(q25;q13). Couple 2 were both carriers of alpha ( SEA) thalassemia mutation. Their chromosome karyotypes were both normal, but had two spontaneous abortions. The couples had received 1 and 3 blastocysts respectively through in vitro fertilization(IVF) cycles. Following the biopsy, the cells underwent whole genome amplification, and the amplified DNA from each embryo was subjected to genetic testing and a 23-chromosome single nucleotide polymorphism(SNP) microarray assay. RESULTS: The embryo of couple 1 was diagnosed as carrier of beta 41/42 thalassemia with euploid chromosomes. The embryo was transferred and resulted in intrauterine pregnancy. Similarly, an embryo of couple 2 was verified as carrier of alpha (-SEA) thalassemia with euploid chromosomes. CONCLUSION: PGD for aneuploidy coupled with testing for single gene disorders via trophectoderm biopsy and whole genome amplification is feasible. The approach can attain diagnosis with minimal damage with sound clinical outcome. PMID- 26829723 TI - [Application of fluorescent in situ hybridization in primary diagnosis of aplastic anemia by morphology]. AB - OBJECTIVE: To investigate the clinical application of fluorescent in situ hybridization (FISH) for the differential diagnosis of myelodysplastic syndromes (MDS) and aplastic anemia (AA). METHODS: A FISH kit capable of detecting the chromosomal abnormalities related to MDS was used to analyze 94 patients who were suspected to have AA by bone marrow morphology. RESULTS: Cytogenetic abnormalities were detected in 11 of the 94 patients, which included trisomy 8 (5 cases), 20q- (1 case) and -Y (1 case). There were 4 cases related to MDS, which included 3 cases of 5q-, in which 1 case carry 20q- at the same time, and 7q- (1 case). No significant difference was found between the MDS and AA groups in terms of age, sex or routine blood examination including absolute neutrophil count, hemoglobin content and platelet count. CONCLUSION: FISH can detect certain cytogenetic abnormalities related to MDS in patients morphologically diagnosed as AA. PMID- 26829724 TI - [Application of eight-probe fluorescence in situ hybridization and R-banding karyotype analysis for the diagnosis of acute lymphoblastic leukemia]. AB - OBJECTIVE: To assess the value of eight-probe fluorescence in situ hybridization (FISH) and R-banding karyotype analysis for the diagnosis of acute lymphoblastic leukemia (ALL). METHODS: With the eight-probe FISH (using probes for MYC, P16, E2A, CHIC2/D10Z1/D17Z1, TEL/AMLl, MLL, BCR/ABL1, and IGH) and R-banding karyotype analysis, 237 cases of ALL were analyzed. RESULTS: Cytogenetic changes were detected in 135 (56.96%) of all cases, which have involved MYC, P16, E2A, CHIC2/D10Z1/D17Z1, TEL/AMLl, MLL, BCR/ABL1, and IGH polyploidies. R-banding karyotype analysis has only detected abnormalities in 48 of such cases, in addition with 14 abnormalities missed by the FISH probes, which have given a total positive rate of 26.16%. The detection rate of the two methods has differed significantly(P<0.05). CONCLUSION: Compared with the R-banding karyotype analysis, the eight-probe FISH is more accurate and efficient. Diagnosis of cytogenetic abnormalities for children with ALL using the combined method can provide a basis for evaluation of prognosis as well as personalized therapy. PMID- 26829725 TI - [Clinical significance of detecting t(11;14) by fluorescence in situ hybridization for the diagnosis of 7 patients with atypical mantle cell lymphoma]. AB - OBJECTIVE: To study the clinical features and diagnosis of 7 patients with atypical mantle cell lymphoma (MCL). METHODS: The 7 MCL patients were misdiagnosed as chronic lymphocytic leukemia (CLL) due to a score of 4 for their immunophenotypes. The clinical features and diagnosis of such patients were retrospectively analyzed. RESULTS: Six patients had superficial lymphadenectasis but their lymph nodes could not be palpated. All 7 patients were as stage IV considering bone marrow infiltration. Scores of immunophenotype of CLL were 4, and interphase fluorescence in situ hybridization (FISH) for t(11;14) were positive in all patients. CONCLUSION: Some MCL patients have clinical features similar to CLL. Interphase FISH can play an important role in the diagnosis of MCL. PMID- 26829726 TI - [Study of in vitro expression of human platelet ITGB3 gene nonsense mutation c.1476G>A]. AB - OBJECTIVE: To explore the function of a novel nonsense mutation c.1476G>A of ITGB3 gene using an in vitro expression system. METHODS: An eukaryotic expression vector containing ITGB3 c.1476G>A cDNA was generated by site-directed mutagenesis and transformed into E.coli. Plasmid DNA was extracted and sequenced to confirm the target mutations. Wild-type and mutant recombination plasmids were transfected into Chinese hamster ovarian cancer (CHO) cells by nonliposome method, and the stable expression cells were harvested by G418 screening. The ITGB3 gene mRNA transcription and GPIIIa expression level in CHO cells were detected with real-time quantitative PCR, Western blotting and flow cytometry, respectively. RESULTS: The eukaryotic expression vectors of wild ITGB3 cDNA and c.1476G>A mutant were successfully constructed. CHO cells with stable expression were obtained after transfection and screening. Compared with the wild-type transfected cells, the amount of CD61 antigen expression was 37% and mRNA transcription level was only 6% in the mutant-transfected cells. Full length GPIIIa protein was found only in the stably wild-type-transfected cells, but not in mutant-transfected cells by Western blotting analysis. CONCLUSION: The ITGB3 c.1476G>A mutation can decrease the transcription level and further affect GPIIIa synthesis and CD61 antigen expression. PMID- 26829727 TI - [Calibration of false positive result in detection of BCR/ABL using fluorescence in situ hybridization]. AB - OBJECTIVE: To explore the effect of false positive signals during detection of BCR/ABL fusion gene by fluorescence in situ hybridization (FISH), and develop a method for calibration. METHODS: Normal specimens were mixed with BCR/ABL positive specimens in which presented signal pattern of 1-red-2-green-1-fusion (1R2G1F) using dual color dual fusion (DCDF) probes and 1-red-1-green-1-fusion (1R1G1F) using extra signal (ES) probes in different proportions. Mixed samples were detected using DCDF and ES probes. Results of DCDF probes, ES probe before calibration, ES probes after calibration and theoretical results were compared by binomial distribution in different proportions. RESULTS: The rate of false positive signals has risen with increase of negative rate. A significant difference was found between theoretical proportion and results without calibration in negative level, 5%, 10% and 25% positive level (P<0.05). There was no significant difference between theoretical proportion and results without calibration in 50% and 90% positive level (P>0.05). Also there was no significant difference between theoretical proportion and calibrated results (P>0.05). CONCLUSION: Calibration of FISH result can delimitate the effect of false positives, and can provide more reliable results in cases with low level positive rates. PMID- 26829728 TI - [Molecular epidemiology of G6PD deficiency in Chaozhou area of eastern Guangdong Province]. AB - OBJECTIVE: To determine the incidence and molecular characteristics of G6PD deficiency in Chaozhou region of eastern Guangdong Province. METHODS: G6PD enzyme activity was assayed with an auto-bioanalyzer. Reverse dot blotting (RDB) was used for detecting 6 common G6PD mutations. Samples with no mutation detected by RDB were further sequenced for unknown mutations. RESULTS: The rate of G6PD deficiency was 3.36% (142/4224). 2.33% (47/2013) of males and 4.3% (95/2208) of females were affected. 12 mutations were detected among the 142 patients, which included c.1376G>T, c.1388G>A, c.1024C>T, c.392G>T, c.871G>A, c.95A>G, c.517T>C, c.131C>G, c.1376G>T/c.517T>C, c.871G>A/IVS-1193T>C/c.1311C>T, c.1376G>T/IVS-11, 93T>C/c.1311C>T and c.1376G>T/c.486_34delT (rs3216174). CONCLUSION: The incidence of G6PD deficiency in Chaozhou region was lower than that of the Hakka population of Guangdong Province, and the mutation types were diversely distributed in this region. c.1376G>T, c.1388G>A and c.1024C>T were the most common mutations, which was followed by c.517T>C. In addition, c.131C>G has been first discovered in the Chinese population. c.1376G>T/c.517T>C and c.1376G>T/c.486_34delT(rs3216174) were new types of compound heterozygous mutations in females. PMID- 26829729 TI - [Mutation analysis of 35 Wilson's disease pedigrees]. AB - OBJECTIVE: To analyze the features of genetic mutations underlying Wilson's disease and provide prenatal and presymptomatic diagnosis. METHODS: For 35 pedigrees affected with the disease, the exons and exon-intron boundaries of the ATP7B gene were amplified with polymerase chain reaction and subjected to Sanger sequencing. After the genotypes of parents of the probands were determined, prenatal diagnosis were performed through chorionic villus sampling. RESULTS: The overall rate for mutation detection was 92.9%. A total of 24 distinct mutations were detected, which included 7 novel mutations, i.e., c.3871G>A(p.A1291T), c.2593_2594insGTCA, c.2790_2792delCAT, c.3661_3663delGGG, c.3700delG, c.4094_4097delCTGT, and IVS6+1G>A. Three mutations, including R778L (c.2333G>T)(45.7%), A874V (c.2621C>T)(7.1%) and P992L (c.2975C>T)(7.1%), were relatively common. Two presymptomatic patients were detected through familial screening, for whom treatment was initiated. Prenatal genetic diagnosis has verified three healthy fetuses and one carrier. CONCLUSION: In this study the most popular mutation ofATP7B gene is R778L and 7 novel mutations have been identified in this gene. For pedigrees of Wilson's disease, genetic counseling in addition with prenatal and presymptomatic diagnosis should be provided through Sanger sequencing and haplotype analysis. PMID- 26829730 TI - [Identification of a novel mutation of DSPP gene in a Chinese family affected with dentinogenesis imperfecta shields type II]. AB - OBJECTIVE: To identify the causative mutation in a Chinese family affected with dentinogenesis imperfecta shields type II (DGI-II). METHODS: With informed consent obtained from all participants, peripheral blood or chorionic villi samples were collected from the family members. Genomic DNA was extracted using a standard SDS-proteinase K-phenol/chloroform method. The whole coding region and exon/intron boundaries of the DSPP gene were amplified with polymerase chain reaction (PCR) and subjected to Sanger sequencing. To confirm the pathogenicity of the identified mutation, an Alu I recognition sequence was introduced into the mutant allele using mismatch primers by semi-nested PCR. Restriction fragment length polymorphism (RFLP) analysis was then carried out for all family members and 60 unrelated healthy controls. Meanwhile, mini-DSPP constructs were conducted to confirm the effect of the mutation in vitro. RESULTS: A splicing site mutation, c.52-1G>A, which was located upstream of exon 3, was found in all three patients and the fetus of the proband. Restriction analysis confirmed that all unaffected individuals and the 60 healthy controls did not carry the same mutation. The expression of minigene showed that the exon 3 of the DSPP gene was skipped during the transcription. CONCLUSION: A novel pathogenic splicing mutation c.52-1G>A has been detected in a Chinese family affected with DGI-II, which enabled prenatal diagnosis for the fetus of the proband. PMID- 26829731 TI - [Analysis of genetic mutations and pathogenesis for two children with Omenn syndrome]. AB - OBJECTIVE: To explore the clinical characteristics and genetic mutations in two children with Omenn syndromes. METHODS: Peripheral venous blood samples were collected from 2 children suspected with severe combined immunodeficiency (SCID) and their family members. The samples were subjected to RAG1 and RAG2 gene sequencing and TCR Vbeta subclone analysis. RESULTS: Both patients had recurrent infections, erythroderma rashes and alopecia baldness. One patient has fit with immunophenotype T-B-NK+, while another was consistent with typical Omenn syndrome combined with T+B-NK+ immunophenotype, IgE and eosinophil increase. Both children have carried compound heterozygous mutations of the RAG1 gene. The first patient carried c.1328 G>A (p.R443K) and c.2486-2490delGGAAA (p.R829fsX869) mutations, both were of de novel type. The second patient has carried c.1209C>T (p.R403W) and c.2892delT (p.ASN964LYSfs*14), with c.2892delT (p.ASN964LYSfs*14) being a de novel mutation. The parents of both patients were heterozygous carriers. The same mutations were not found in 100 healthy children. Both patients' 24 TCR Vbeta subfamilies have presented monoclonal or oligoclonal peaks, with TCR Vbeta polymorphism being severely disrupted. CONCLUSION: Three novel mutations have been identified in two children with Omenn syndrome, which featured early onset and rapid progression. Early recognition of the disease and prompt treatment may reduce the mortality. PMID- 26829732 TI - [Identification of a novel ANK1 gene mutation in a newborn with hereditary spherocytosis]. AB - OBJECTIVE: To determine the disease-causing mutation in a newborn with hereditary spherocytosis. METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and her parents. Next-generation sequencing was used to analyze the related genes. Suspected pathogenic mutation was verified with polymerase chain reaction and Sanger sequencing. RESULTS: An insertional mutation g.834_833insC was identified in the coding region of ankyrin-1 (ANK1) gene, which has caused a frame shift, resulting premature termination of protein translation. CONCLUSION: The hereditary spherocytosis in the neonate was probably due to the g.834_833insC mutation of the ANK1 gene. PMID- 26829733 TI - [Analysis of L2HGDH gene mutation in a patient with 2-hydroxyglutaric aciduria]. AB - OBJECTIVE: To explore pathogenic mutation in a family affected with 2 hydroxyglutaric aciduria. METHODS: Exons of 3 candidate genes, including L2HGDH, D2HGDH and SLC25A1, were amplified with polymerase chain reaction and subjected to direct sequencing. RESULTS: DNA sequencing has found that the proband and his affected younger brother have both carried a heterozygous mutation c.845G>A (p.R282Q) in the exon 7 of the L2HGDH gene. The same mutation was not detected in the his sister who was healthy. Pedigree analysis has confirmed that the above mutation was inherited from the mother. No mutation was detected in exons and flanking sequences of the D2HGDH and SLC25A1 genes. CONCLUSION: Mutation of the L2HGDH gene probably underlies the 2-hydroxyglutaric aciduria in this family. PMID- 26829734 TI - [Analysis and prenatal diagnosis of PKLR gene mutations in a family with pyruvate kinase deficiency]. AB - OBJECTIVE: To evaluate the feasibility of genetic and prenatal diagnosis for a family affected with pyruvate kinase deficiency (PKD). METHODS: Targeted sequence capture and high-throughput sequencing technology was used to detect the exons and exon-intron boundaries of the PKLR gene in a clinically suspected PKD patient. Meanwhile, the genotype of the pedigree was validated by Sanger sequencing. Prenatal genetic diagnosis was performed by amniotic fluid sampling after genotype of the mother of the proband was determined. RESULTS: The proband was found to harbor double heterozygous mutations, c.661G>A (Asp221Asn) and c.1528C>T (Arg510Ter), which resulted in amino acid substitution Asp221Asn and Arg510Ter. Such mutations were confirmed by Sanger sequencing. The mother and father of the proband were detected to have respectively carried c.1528C>T (Arg510Ter) and c.661G>A (Asp221Asn) mutation. The fetus was found to have carried the same mutations as the proband. Following selected abortion, analysis of fetal tissue was consistent with the result of prenatal diagnosis. CONCLUSION: The compound mutations of c.661G>A and c.1528C>T of PKLR gene probably underlie the PKD in the family. Prenatal diagnosis of the mutations analysis can facilitate detection of affected fetus in time. PMID- 26829735 TI - [Mutation analysis for a family affected with Charcot-Marie-Tooth disease type 4C]. AB - OBJECTIVE: To identify potential mutation in a Chinese family affected with Charcot-Marie-Tooth disease(CMT). METHODS: Clinical data of the family was collected, and genomic DNA was extracted from peripheral blood samples of the family members. Seventy-two candidate genes of the proband were captured and sequenced by targeted next-generation sequencing, and the results were confirmed by Sanger sequencing. The protein structure was predicted with PyMOL-1 software. RESULTS: A homozygous missense mutation c.1894G>A(p.E632K) was identified in the exon 11 of the SH3TC2 gene in the proband. Heterozygous c.1894G>A mutation was also detected in the proband's father, mother and daughter, but not in the healthy family members and 300 normal controls. Retrieval of the NCBI, HGMD and 1000 genome databases has verified the c.1894G>A to be as a novel mutation. Computer simulation has suggested that the mutation has altered the 3D structure of the SH3TC2 protein. CONCLUSION: The proband was diagnosed as CMT4C, for which the underlying gene was SH3TC2. This finding has expanded the spectrum of SH3TC2 mutation in association with CMT4C. PMID- 26829736 TI - [Analysis of PRRT2 gene mutations in a Chinese family affected with paroxysmal kinesigenic dyskinesia]. AB - OBJECTIVE: To screen potential mutations of PRRT2 gene in a Chinese family affected with paroxysmal kinesigenic dyskinesia (PKD). METHODS: Polymerase chain reaction, DNA sequencing and restriction endonuclaese analysis were used to analyze all members of the family. RESULTS: A heterozygous mutation c.649dupC was identified in the PRRT2 gene in all patients, while no similar mutation was found in healthy members from the family. CONCLUSION: The c.649dupC mutation of the PRRT2 gene probably underlies the PKD in this family. Prenatal diagnosis can reduce the risk for further birth of affected children for this family. PMID- 26829738 TI - [Genotype and phenotype analysis of two patients with Williams syndrome]. AB - OBJECTIVE: To perform genetic analysis for two patients with supravalvular aortic stenosis and unusual facial features. METHODS: Cytogenetic and molecular genetic methods including chromosome karyotyping, multiplex ligation-dependent probe amplification (MLPA) and single nucleotide polymorphism array (SNP-array) were performed to detect potential mutation in the patients. RESULTS: No abnormal karyotype was detected in either patient. Deletions in 7q11.23 region (1.36 Mb and 1.73 Mb, respectively) were discovered by SNP-array for the two patients. In both patients, de novo heterozygous deletion of ELN and LIMK1 genes was confirmed by MLPA analysis. CONCLUSION: The genotypes of the two patients were identified by molecular genetic analysis, which has facilitated interpretation of the phenotypes of these patient. According to the deletion mutation, prenatal diagnosis for the family could be performed in the future. PMID- 26829737 TI - [A novel homozygous mutation in PLA2G6 gene causes infantile neuroaxonal dystrophy in a case]. AB - OBJECTIVE: To investigate the clinical symptoms and potential mutations in the PLA2G6 gene for a child with infantile neuroaxonal dystrophy. METHODS: Clinical data of the patient was collected. The coding regions of PLA2G6 gene was subjected to Sanger sequencing using blood DNA from the patient and her parents. RESULTS: The patient has presented with psychomotor regression and hypotonia, followed by development of tetraparesis. A novel homozygous mutation G68A in the PLA2G6 gene was found by DNA sequencing, while her parents were both heterozygous carriers. CONCLUSION: The psychomotor regression and tetraparesis of the patient was caused by infantile neuroaxonal dystrophy due to a novel homozygous mutation in the PLA2G6 gene, which was inherited from her parents. PMID- 26829739 TI - [Analysis of genetics mechanism for the phenotypic diversity in a patient carrying a rare ring chromosome 9]. AB - OBJECTIVE: To explore the genetics mechanism for the phenotypic variability in a patient carrying a rare ring chromosome 9. METHODS: The karyotype of the patient was analyzed with cytogenetics method. Presence of sex chromosome was confirmed with fluorescence in situ hybridization. The SRY gene was subjected to PCR amplification and direct sequencing. Potential deletion and duplication were detected with array-based comparative genomic hybridization (array-CGH). RESULTS: The karyotype of the patient has comprised 6 types of cell lines containing a ring chromosome 9. The SRY gene sequence was normal. By array-CGH, the patient has carried a hemizygous deletion at 9p24.3-p23 (174 201-9 721 761) encompassing 30 genes from Online Mendelian Inheritance in Man. CONCLUSION: The phenotypic variability of the 9p deletion syndrome in conjunct with ring chromosome 9 may be attributable to multiple factors including loss of chromosomal material, insufficient dosage of genes, instability of ring chromosome, and pattern of inheritance. PMID- 26829740 TI - [Cytogenetic and molecular genetic analysis of a case with mosaic marker chromosomes]. AB - OBJECTIVE: To explore the source of small supernumerary marker chromosome in a case. METHODS: G-banded karyotyping, fluorescence in situ hybridization, multiple sequence tagged sites (STS) of the Y chromosome, and Illumima Human Cyto SNP-12 Beadchip analysis were carried out. RESULTS: The karyotype was mos 46,X,+mar1[21]/46,X,+mar2[78]. Y chromosome STS analysis has displayed the presence of sy84, sY86, USP9Y and DDX3Y genes from the AZFa region, and sY1227 of the AZFb region, while sY1228, sY1015, sY127, sY134 from the AZFb region, and sY254 and sY255 from the AZFc region were missing. FISH analysis has verified both of the marker chromosomes to be Y chromosome fragments. Mar1 was ish.idic(Y)(q11.2)(SRY++,DXZ1+,DYZ3++,DYZ1-), while mar2 was ish.del(Y)(q11.2)(SRY+,DXZ1+,DYZ3+,DYZ1-). Single nucleotide polymorphism (SNP) microarray analysis showed that the Yq11.2-Yq12 has lost a 10.81 Mb fragment. CONCLUSION: The marker chromosomes were verified to be aberrant Y chromosomes, with the breakage and recombination occurring in Yq11.2. Mar 1 was an isodicentric Y chromosome (idic(Y)pter to q11.2::q11.2 to pter), and mar2 was del(Y)(q11.2). The karyotype was mos 46,X,ish idic(Y)(q11.2)(DYZ3++,SRY++,DXZ1+,DYZ1-)[21]/46,X,ish del(Y)(q11.2)(DYZ3+,SRY+,DXZ1+,DYZ1-)[78]. Combined FISH, Y chromosome STS analysis, SNP microarray analysis and other technologies can facilitate determination of the nature of marker chromosomes. PMID- 26829741 TI - [Analysis of the association of human leukocyte antigen DQ gene polymorphisms with unexplained recurrent spontaneous abortion among ethnic Han Chinese from Wenzhou region]. AB - OBJECTIVE: To assess the association of human leukocyte antigen DQ gene polymorphisms with unexplained recurrent spontaneous abortion (URSA) among ethnic Han Chinese from Wenzhou region. METHODS: Fifty couples with URSA (URSA group) and 66 couples with normal pregnancy history (control group) were recruited. The alleles of HLA-DQA1 and HLA-DQB1 were analyzed by polymerase chain reaction with specific sequence primers (PCR-SSP) in all subjects. The frequency distribution of HLA-DQ alleles, odds ratios (OR) between each group and sharing of HLA-DQ alleles were calculated. RESULTS: The frequency distribution of HLA-DQB1*03:03 allele in the females with URSA was significantly higher than that healthy females (21.00% vs. 9.85%, OR=2.433, 95%CI: 1.232-4.894, chi(2)=5.657, P<0.05). The HLA-DQB1*05:03 allele was present among the healthy females with a frequency of 3.03%, and was not detected among females with URSA. For both males and females, the HLA-DQB1*05:02 allele were only typed in control group with frequencies of 6.06% and 5.30%, respectively. The sharing of HLA-DQA1 alleles in couples with URSA was increased compared with the control group (70.27% vs. 44.64%, OR=2.931, 95%CI: 1.216-7.067, P<0.05). CONCLUSION: The increased sharing of HLA-DQA1 alleles may contribute to the susceptibility of URSA among ethnic Han Chinese from Wenzhou region. The allele of HLA-DQB1*03:03 in the females may be predisposing factor for URSA. However, the HLA-DQB1*05:02 allele in both gender and HLA-DQB1*05:03 allele in females may confer a protective effect. PMID- 26829742 TI - [Interaction of MIF gene -173G/C polymorphism and GPX1 gene 594C/T polymorphism with high-fat diet in ulcerative colitis]. AB - OBJECTIVE: To investigate the interaction of single nucleotide polymorphisms of macrophage migration inhibitory factor (MIF) gene -173G/C and glutathione peroxidase 1(GPX1) gene 594C/T polymorphisms and high-fat diet in ulcerative colitis (UC). METHODS: The genetic polymorphisms of MIF -173G/C and GPX1 594C/T were determined with a polymorphism-polymerase chain reaction (PCR)-endonuclease method in peripheral blood leukocytes derived from 1500 UC cases and 1500 healthy controls. RESULTS: The frequencies of MIF -173CC and GPX1 594TT were 55.60% and 55.73% in the UC cases and 16.67% and 16.47% in the healthy controls, respectively. Statistical tests also showed a significant difference in the frequencies between the two groups (P<0.01; P<0.01, respectively). Individuals carrying MIF -173CC also had a significantly higher risk of UC compared with those with MIF -173GG (OR=6.8662, 95%CI: 4.5384-9.6158). Individuals carrying GPX1 594TT had a high risk of UC (OR=7.0854, 95%CI: 4.4702-10.5283). Combined analysis showed that the percentages of MIF -173CC/GPX1 594TT in the UC and control groups were 31.00% and 2.73%, respectively (P<0.01). Individuals carrying MIF -173CC/GPX1 594TT had a high risk of UC (OR=49.0113, 95%CI: 31.7364-61.8205). The high-fat diet rate of the case group was significantly higher than that of the control group (OR=3.3248, 95%CI: 1.9461-5.0193, P<0.01), and statistic analysis suggested an interaction between high-fat diet and MIF -173CC and GPX1 594TT which increase risk of UC (gamma =6.9293; gamma =6.9942). CONCLUSION: MIF 173CC and GPX1 594TT and high-fat diet are the risk factors for UC, and the significant interactions between genetic polymorphisms of MIF -173G/C, GPX1 594C/T and high-fat diet may increase the risk for UC. PMID- 26829743 TI - [Association of CETP gene I405V/D442G polymorphisms with cerebral hemorrhage and serum lipid profile in ethnic Han population from Changsha]. AB - OBJECTIVE: To assess the association between I405V and D442G polymorphisms of the CETP gene with cerebral hemorrhage (CH) and a related lipid profile among ethnic Han Chinese from Changsha. METHODS: A case-control study was carried out, which enrolled 170 cerebral hemorrhage patients and 191 ethnicity-, age- and sex matched health controls. Polymerase chain reaction-restricted fragments length polymorphism (PCR-RFLP) was used to determine the polymorphisms. Lipid profile was determined by means of oxidase method. Statistic analyses were performed with SPSS 16.0. RESULTS: No significant difference was found in the CETP gene I405V and D442G genotypes and allelic distribution between the CH patients and controls (P>0.05). There was no association between CETP gene I405V polymorphism and lipid profile in both groups (P>0.05). CH patients with DG genotype of the D442G polymorphism had higher TC and low density lipoprotein-cholesterol (LDL-C) levels than those with a DD genotype(P<0.05). CONCLUSION: CETP gene I405V polymorphism may not be associated with CH among ethnic Han Chinese from Changsha, while the D442G polymorphism of the CETP gene may be associated with TC and LDL levels in the same population. PMID- 26829744 TI - [Association of copy number variation of exon 11 of IL-23 receptor gene with susceptibility to tuberculosis among Chinese Uygurs]. AB - OBJECTIVE: To assess the association of copy number variations (CNVs) of exon 11 of IL-23 receptor gene with susceptibility to active pulmonary tuberculosis among Chinese Uygurs. METHODS: In this study, 250 subjects with active pulmonary tuberculosis (PTB) and 250 normal controls were recruited. A paired case-control study was conducted in the Chinese Uygur population in Xinjiang and the CNV of IL 23R was analyzed using Taqman real-time PCR. RESULTS: The study showed that the frequencies of different copy number in exon 11 of IL-23R between PTB and control groups were statistically significant (chi(2)=13.35, P<0.01). There were significant difference in CNV of exon 11 in IL-23R between PTB patients and controls (chi(2)=14.95, P<0.01, OR=2.875, 95%CI: 1.655-4.994). The increase of copy number in exon 11 of IL-23R showed significantly different between PTB and control groups (chi(2)=10.475, P=0.0012, OR=2.611, 95%CI: 1.437-4.744). CONCLUSION: The CNV of exon 11 in IL-23R is associated with PTB in the Chinese Uygur population. The increase of the copy number in exon 11 of IL-23R may be a risk factor for PTB in Chinese Uygurs. PMID- 26829745 TI - [Progress in research on defective protein trafficking and functional restoration in HERG-associated long QT syndrome]. AB - The human ether-a-go-go related gene (HERG) encodes the alpha -subunit of the rapid component of the delayed rectifier K(+) channel, which is essential for the third repolarization of the action potential of human myocardial cells. Mutations of the HERG gene can cause type II hereditary long QT syndrome (LQT2), characterized by prolongation of the QT interval, abnormal T wave, torsade de pointes, syncope and sudden cardiac death. So far more than 300 HERG mutations have been identified, the majority of which can cause LQT2 due to HERG protein trafficking defect. It has been reported that certain drugs can induce acquired long QT syndrome through directly blocking the pore and/or affecting the HERG trafficking. The trafficking defects and K(+) currents can be restored with low temperature and certain drugs. However, the mechanisms underlying defective trafficking caused by HERG mutations and the inhibition/restoration of HERG trafficking by drugs are still unknown. This review summarizes the current understanding of the molecular mechanisms including HERG trafficking under physiological and pathological conditions, and the effects of drugs on the HERG trafficking, in order to provide theoretical evidence for the diagnosis and treatment of long QT syndrome. PMID- 26829746 TI - [Progress in genetic research on pachydermoperiostosis]. AB - Pachydermoperiostosis is a rare genetic disease characterized by finger clubbing, periostosis, cutis verticis gyrata and pachydermia accompanied by acroosteolysis and hyperhidrosis. Recently, two susceptibility genes, HPGD and SLCO2A1, have been identified, whose protein products are involved in the transportation of prostaglandin and metabolism underlying pachydermoperiostosis. Here the genetic basis of pachydermoperiostosis and its correlation with its clinical phenotype are reviewed, which may provide a reference for basic research and clinic diagnosis for the disease. PMID- 26829747 TI - [Preaxial polydactyly in a pedigree]. PMID- 26829748 TI - Dietary Micronutrient Intake and Micronutrient Status in Patients With Chronic Stable Heart Failure: An Observational Study. AB - BACKGROUND: Observational studies suggest that patients with heart failure have a tendency to a reduced status of a number of micronutrients and that this may be associated with an adverse prognosis. A small number of studies also suggest that patients with heart failure may have reduced dietary intake of micronutrients, a possible mechanism for reduced status. OBJECTIVE: The aims of this study were to assess dietary micronutrient intake and micronutrient status in a group of patients with heart failure. METHODS: Dietary intake was assessed in 79 outpatients with chronic stable heart failure with a reduced ejection fraction using a validated food frequency questionnaire. Blood concentrations of a number of micronutrients, including vitamin D, were measured in fasting blood samples, drawn at the time of food frequency questionnaire completion. RESULTS: More than 20% of patients reported intakes less than the reference nutrient intake or recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, and iodine. More than 5% of patients reported intakes less than the lower reference nutrient intake or minimum recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, selenium, and iodine. Vitamin D deficiency (plasma total 25-hydroxy-vitamin D concentration <50 nmol/L) was observed in 75.6% of patients. CONCLUSIONS: Vitamin D deficiency was common in this group of patients with heart failure. Based on self-reported dietary intake, a substantial number of individuals may not have been consuming enough vitamin D and a modest number of individuals may not have been consuming enough riboflavin, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, or iodine to meet their dietary needs. PMID- 26829749 TI - HLA class II sequence variants influence tuberculosis risk in populations of European ancestry. AB - Mycobacterium tuberculosis infections cause 9 million new tuberculosis cases and 1.5 million deaths annually. To identify variants conferring risk of tuberculosis, we tested 28.3 million variants identified through whole-genome sequencing of 2,636 Icelanders for association with tuberculosis (8,162 cases and 277,643 controls), pulmonary tuberculosis (PTB) and M. tuberculosis infection. We found association of three variants in the region harboring genes encoding the class II human leukocyte antigens (HLAs): rs557011[T] (minor allele frequency (MAF) = 40.2%), associated with M. tuberculosis infection (odds ratio (OR) = 1.14, P = 3.1 * 10(-13)) and PTB (OR = 1.25, P = 5.8 * 10(-12)), and rs9271378[G] (MAF = 32.5%), associated with PTB (OR = 0.78, P = 2.5 * 10(-12))--both located between HLA-DQA1 and HLA-DRB1--and a missense variant encoding p.Ala210Thr in HLA DQA1 (MAF = 19.1%, rs9272785), associated with M. tuberculosis infection (P = 9.3 * 10(-9), OR = 1.14). We replicated association of these variants with PTB in samples of European ancestry from Russia and Croatia (P < 5.9 * 10(-4)). These findings show that the HLA class II region contributes to genetic risk of tuberculosis, possibly through reduced presentation of protective M. tuberculosis antigens to T cells. PMID- 26829750 TI - An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma. AB - Translocation events are frequent in cancer and may create chimeric fusions or 'regulatory rearrangements' that drive oncogene overexpression. Here we identify super-enhancer translocations that drive overexpression of the oncogenic transcription factor MYB as a recurrent theme in adenoid cystic carcinoma (ACC). Whole-genome sequencing data and chromatin maps highlight distinct chromosomal rearrangements that juxtapose super-enhancers to the MYB locus. Chromosome conformation capture confirms that the translocated enhancers interact with the MYB promoter. Remarkably, MYB protein binds to the translocated enhancers, creating a positive feedback loop that sustains its expression. MYB also binds enhancers that drive different regulatory programs in alternate cell lineages in ACC, cooperating with TP63 in myoepithelial cells and a Notch program in luminal epithelial cells. Bromodomain inhibitors slow tumor growth in ACC primagraft models in vivo. Thus, our study identifies super-enhancer translocations that drive MYB expression and provides insight into downstream MYB functions in alternate ACC lineages. PMID- 26829752 TI - A single three-dimensional chromatin compartment in amphioxus indicates a stepwise evolution of vertebrate Hox bimodal regulation. AB - The HoxA and HoxD gene clusters of jawed vertebrates are organized into bipartite three-dimensional chromatin structures that separate long-range regulatory inputs coming from the anterior and posterior Hox-neighboring regions. This architecture is instrumental in allowing vertebrate Hox genes to pattern disparate parts of the body, including limbs. Almost nothing is known about how these three dimensional topologies originated. Here we perform extensive 4C-seq profiling of the Hox cluster in embryos of amphioxus, an invertebrate chordate. We find that, in contrast to the architecture in vertebrates, the amphioxus Hox cluster is organized into a single chromatin interaction domain that includes long-range contacts mostly from the anterior side, bringing distant cis-regulatory elements into contact with Hox genes. We infer that the vertebrate Hox bipartite regulatory system is an evolutionary novelty generated by combining ancient long range regulatory contacts from DNA in the anterior Hox neighborhood with new regulatory inputs from the posterior side. PMID- 26829751 TI - MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism. AB - Angiocentric gliomas are pediatric low-grade gliomas (PLGGs) without known recurrent genetic drivers. We performed genomic analysis of new and published data from 249 PLGGs, including 19 angiocentric gliomas. We identified MYB-QKI fusions as a specific and single candidate driver event in angiocentric gliomas. In vitro and in vivo functional studies show that MYB-QKI rearrangements promote tumorigenesis through three mechanisms: MYB activation by truncation, enhancer translocation driving aberrant MYB-QKI expression and hemizygous loss of the tumor suppressor QKI. To our knowledge, this represents the first example of a single driver rearrangement simultaneously transforming cells via three genetic and epigenetic mechanisms in a tumor. PMID- 26829755 TI - Hydrogen-Transfer-Mediated Direct beta-Alkylation of Aryl-1,8-naphthyridines with Alcohols under Transition Metal Catalyst Free Conditions. AB - By employing abundant and sustainable alcohols as the alkylating reagents, a new and direct alkylation method has been demonstrated. This method enables the selective alkylation of the less substituted pyridyl ring at the beta-site of aryl-1,8-naphthyridines, affording the desired products in moderate to excellent yields upon isolation. The method proceeds under transition-metal-free conditions in an atom- and step-economic fashion and liberates water as the sole byproduct. Mechanistic investigations suggest the reaction undergoes a hydrogen-transfer mediated alkylation mode. PMID- 26829754 TI - Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity. AB - Microbial pathogenesis studies are typically performed with reference strains, thereby overlooking within-species heterogeneity in microbial virulence. Here we integrated human epidemiological and clinical data with bacterial population genomics to harness the biodiversity of the model foodborne pathogen Listeria monocytogenes and decipher the basis of its neural and placental tropisms. Taking advantage of the clonal structure of this bacterial species, we identify clones epidemiologically associated either with food or with human central nervous system (CNS) or maternal-neonatal (MN) listeriosis. The latter clones are also most prevalent in patients without immunosuppressive comorbidities. Strikingly, CNS- and MN-associated clones are hypervirulent in a humanized mouse model of listeriosis. By integrating epidemiological data and comparative genomics, we have uncovered multiple new putative virulence factors and demonstrate experimentally the contribution of the first gene cluster mediating L. monocytogenes neural and placental tropisms. This study illustrates the exceptional power in harnessing microbial biodiversity to identify clinically relevant microbial virulence attributes. PMID- 26829753 TI - The genomic basis of parasitism in the Strongyloides clade of nematodes. AB - Soil-transmitted nematodes, including the Strongyloides genus, cause one of the most prevalent neglected tropical diseases. Here we compare the genomes of four Strongyloides species, including the human pathogen Strongyloides stercoralis, and their close relatives that are facultatively parasitic (Parastrongyloides trichosuri) and free-living (Rhabditophanes sp. KR3021). A significant paralogous expansion of key gene families--families encoding astacin-like and SCP/TAPS proteins--is associated with the evolution of parasitism in this clade. Exploiting the unique Strongyloides life cycle, we compare the transcriptomes of the parasitic and free-living stages and find that these same gene families are upregulated in the parasitic stages, underscoring their role in nematode parasitism. PMID- 26829756 TI - Clay mineralogy indicates a mildly warm and humid living environment for the Miocene hominoid from the Zhaotong Basin, Yunnan, China. AB - Global and regional environmental changes have influenced the evolutionary processes of hominoid primates, particularly during the Miocene. Recently, a new Lufengpithecus cf. lufengensis hominoid fossil with a late Miocene age of ~6.2 Ma was discovered in the Shuitangba (STB) section of the Zhaotong Basin in Yunnan on the southeast margin of the Tibetan Plateau. To understand the relationship between paleoclimate and hominoid evolution, we have studied sedimentary, clay mineralogy and geochemical proxies for the late Miocene STB section (~16 m thick; ca. 6.7-6.0 Ma). Our results show that Lufengpithecus cf. lufengensis lived in a mildly warm and humid climate in a lacustrine or swamp environment. Comparing mid to late Miocene records from hominoid sites in Yunnan, Siwalik in Pakistan, and tropical Africa we find that ecological shifts from forest to grassland in Siwalik are much later than in tropical Africa, consistent with the disappearance of hominoid fossils. However, no significant vegetation changes are found in Yunnan during the late Miocene, which we suggest is the result of uplift of the Tibetan plateau combined with the Asian monsoon geographically and climatically isolating these regions. The resultant warm and humid conditions in southeastern China offered an important refuge for Miocene hominoids. PMID- 26829758 TI - State-of-the-art technologies for rapid and high-throughput sample preparation and analysis of N-glycans from antibodies. AB - Glycosylation is a PTM that occurs during production of many protein-based biologic drugs and can have a profound impact on their biological, clinical, and pharmacological properties. Quality by design, process optimization, and advance in manufacturing technology create a demand for robust, sensitive, and accurate profiling and quantification of antibody glycosylation. Potential drawbacks in antibody glycosylation profiling include the high hands-on time required for sample preparation and several hours for data acquisition and analysis. Rapid and high-throughput (HTP) N-glycan profiling and characterization along with automation for sample preparation and analysis are essential for extensive antibody glycosylation analysis due to the substantial improvement of turnaround time. The first part of this review article will focus on the recent progress in rapid and HTP sample preparation and analysis of antibody glycosylation. Subsequently, the article will cover a brief overview of various separation and mass spectrometric methods for the rapid and HTP analysis of N-glycans in antibodies. Finally, we will discuss the recent developments in process analytical technologies for the screening and quantification of N-glycans in antibodies. PMID- 26829757 TI - SPLINTS: small-molecule protein ligand interface stabilizers. AB - Regulatory protein-protein interactions are ubiquitous in biology, and small molecule protein-protein interaction inhibitors are an important focus in drug discovery. Remarkably little attention has been given to the opposite strategy stabilization of protein-protein interactions, despite the fact that several well known therapeutics act through this mechanism. From a structural perspective, we consider representative examples of small molecules that induce or stabilize the association of protein domains to inhibit, or alter, signaling for nuclear hormone, GTPase, kinase, phosphatase, and ubiquitin ligase pathways. These SPLINTS (small-molecule protein ligand interface stabilizers) drive interactions that are in some cases physiologically relevant, and in others entirely adventitious. The diverse structural mechanisms employed suggest approaches for a broader and systematic search for such compounds in drug discovery. PMID- 26829759 TI - Determinants of Admission to Inpatient Rehabilitation Among Acute Care Survivors of Hypoxic-Ischemic Brain Injury: A Prospective Population-Wide Cohort Study. AB - OBJECTIVE: To investigate demographic and acute care clinical determinants of admission to inpatient rehabilitation (IR) among patients with hypoxic-ischemic brain injury (HIBI) who survive the initial acute care episode. DESIGN: Population-wide prospective cohort study using Canadian Institutes for Health Information administrative health data from Ontario, Canada. All patients who survived their HIBI acute care episode during the study period remained eligible for the outcome, admission to IR, for 1 year postacute care discharge. SETTING: Inpatient rehabilitation. PARTICIPANTS: We included all patients with HIBI using International Classification of Diseases, Tenth Revision, Canadian Enhancement codes recorded at acute care admission who were >=20 years old (N=599) and discharged from acute care between the 2002 and 2010 fiscal years, inclusive. Six patients were excluded from analyses because of missing data. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Admission to IR. RESULTS: Of HIBI survivors admitted to IR within 1 year of acute care discharge (n=169), most (56.2%) had an IR admitting diagnosis indicating anoxic brain damage. Younger age, being a man, lower comorbidity burden, longer length of stay of preceding acute care episode, and shorter duration in special care were most predictive of admission to IR in multivariable regression models. Women had an almost 2-fold lower incidence of admission to IR (risk ratio, .62; 95% confidence interval, .46-.84). CONCLUSIONS: Older age, higher comorbidity burden, and shorter lengths of stay and delayed discharge from acute care are associated with lower incidence of IR admission for patients with HIBI. That women are almost 2-fold less likely to receive rehabilitation requires further investigation. PMID- 26829760 TI - Effect of Manual Lymphatic Drainage After Total Knee Arthroplasty: A Randomized Controlled Trial. AB - OBJECTIVE: To evaluate the effects of manual lymphatic drainage (MLD) on knee swelling and the assumed consequences of swelling after total knee arthroplasty (TKA). DESIGN: Randomized controlled trial. SETTING: Primary care hospital. PARTICIPANTS: Two groups of 30 patients were randomized before TKA surgery (N=60; 65% women [39]; mean age, 70.7+/-8.8y; weight, 77.8+/-11.3kg; size, 1.64+/-0.08m; body mass index, 29.9+/-4.1kg/m(2)). INTERVENTIONS: Participants received either 5 MLD treatments or a placebo, added to rehabilitation, in between the second day and the seventh day after surgery. MAIN OUTCOME MEASURES: Swelling was measured by blinded evaluators before surgery and at second day, seventh day, and 3 months using bioimpedance spectroscopy and volume measurement. Secondary outcomes were active and passive range of motion, pain, knee function, and gait parameters. RESULTS: At seventh day and 3 months, no outcome was significantly different between groups, except for the knee passive flexion contracture at 3 months, which was lower and less frequent in the MLD group (-2.6 degrees ; 95% confidence interval, -5.0 degrees to -0.21 degrees ; P=.04; absolute risk reduction, 26.6%; 95% confidence interval, 0.9%-52.3%; number needed to treat, 4). The mean pain level decreased between 5.8 and 8.2mm on the visual analog scale immediately after MLD, which was significant after 4 of 5 MLD treatments. CONCLUSIONS: MLD treatments applied immediately after TKA surgery did not reduce swelling. It reduced pain immediately after the treatment. Further studies should investigate whether the positive effect of MLD on knee extension is replicable. PMID- 26829761 TI - Manual Tactile Test Predicts Sensorimotor Control Capability of Hands for Patients With Peripheral Nerve Injury. AB - OBJECTIVES: To comprehend the merits of a Manual Tactile Test (MTT) in assessing hand sensorimotor functions by exploring the relations among 3 subtests along with the precision pinch performances for patients with peripheral nerve injuries (PNIs); and to understand the accuracy of the MTT by constructing the sensitivity and specificity of the test for patients with PNI. DESIGN: Case-control study. SETTING: Hospital and local community. PARTICIPANTS: Patients with PNI (n=28) were recruited along with age-, sex-, and handedness-matched healthy controls (n=28) (N=56). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Semmes Weinstein monofilament, moving and static 2-point discrimination, roughness differentiation, stereognosis and barognosis subtests of the MTT, and precision pinch performance were used to examine the sensory and sensorimotor status of the hand. RESULTS: The worst results in all sensibility tests were found for the patients with PNI (P<.001) in comparison with the controls. Multiple linear regression analysis showed the MTT was a better indicator for predicting the sensorimotor capacity of hands in the patients with PNI (r(2)=.189, P=.003) than the traditional test (r(2)=.088, P=.051). The results of the receiver operating characteristic curve estimation show that the area under the curve was .968 and .959 for the roughness differentiation and stereognosis subtests, respectively, and .853 for the barognosis subtest, therefore revealing the accuracy of the MTT in assessing sensorimotor status for patients with PNI. CONCLUSIONS: This study indicates that the MTT is highly accurate and a significant predictor of sensorimotor performance in hands of patients with PNI. The MTT could therefore help clinicians obtain a better understanding of the sensorimotor and functional status of the hand with nerve injuries. PMID- 26829762 TI - Distinguishing the influence of task difficulty on error-related ERPs using surface Laplacian transformation. AB - Electrophysiologically, errors are characterized by a negative deflection, the error related negativity (ERN), which is followed by the error positivity (Pe). However, it has been suggested that this latter component consists of two subcomponents, with an early frontocentral Pe reflecting a continuation of the ERN, and a centro-parietal Pe reflecting error awareness. Using Laplacian transformed averages, a correct-related negativity (CRN; similar to the ERN), can be found on correct trials. As this technique allows for the decomposition of the recorded scalp potentials resulting in a better dissociation of the underlying brain activities, Laplacian transformation was used in the present study to differentiate between both the ERN/CRN and both Pe components. Additionally, task difficulty was manipulated. Our results show a clearly distinguishable early and late Pe. Both the ERN/CRN and the early Pe varied with task difficulty, showing decreased ERN/early Pe in the difficult condition. However, the late Pe was not influenced by our difficulty manipulation. This suggests that the early and the late Pe reflect qualitatively different processes. PMID- 26829763 TI - Intermittent intraoperative nerve monitoring in thyroid reoperations: Preliminary results of a randomized, single-surgeon study. AB - BACKGROUND: The purpose of this study was to evaluate whether intermittent intraoperative nerve monitoring (IONM) could reduce the incidence of recurrent laryngeal nerve (RLN) paralysis in thyroid reoperations. METHODS: Enrolled patients were randomly assigned into the nerve integrity monitor (NIM) group and the control group. RESULTS: The incidence of temporary RLN paralysis and permanent RLN paralysis was 12.2% and 4.9% in the NIM group compared with 7.0% and 2.3% in the control group (p = .658 and p = .966, respectively). The incidence of surgeon-related paralysis, tumor-related paralysis, and scar-related paralysis was 4.9%, 7.3%, and 4.9% in the NIM group compared with 4.7%, 2.3%, and 2.3% in the control group, respectively (p = 1, p = .575, and p = .966, respectively). CONCLUSION: Intermittent IONM could not provide additional benefits to reduce the incidence of temporary RLN paralysis and permanent RLN paralysis in thyroid reoperations. It could not reduce the incidence of paralysis caused by unintentional injuries. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1993-E1997, 2016. PMID- 26829764 TI - Quantifying the impact of traffic-related air pollution on the indoor air quality of a naturally ventilated building. AB - Improper natural ventilation practices may deteriorate indoor air quality when in close proximity to roadways, although the intention is often to reduce energy consumption. In this study, we employed a CFD-based air quality model to quantify the impact of traffic-related air pollution on the indoor air quality of a naturally ventilated building. Our study found that the building envelope restricts dispersion and dilution of particulate matter. The indoor concentration in the baseline condition located 10m away from the roadway is roughly 16-21% greater than that at the edge of the roadway. The indoor flow recirculation creates a well-mixed zone with little variation in fine particle concentration (i.e., 253nm). For ultrafine particles (<100nm), a noticeable decrease in particle concentrations indoors with increasing distance from the road is observed due to Brownian and turbulent diffusion. In addition, the indoor concentration strongly depends on the distance between the roadway and building, particle size, wind condition, and window size and location. A break-even point is observed at D'~2.1 (normalized distance from the roadway by the width of the road). The indoor particle concentration is greater than that at the highway where D'<2.1, and vice versa. For new building planning, the distance from the roadway and the ambient wind condition need to be considered at the early design stage whereas the size and location of the window openings, the interior layout, and the placement of fresh air intakes are important to the indoor air quality of existing buildings adjacent to roadways. PMID- 26829765 TI - Prefrontal white matter pathology in air pollution exposed Mexico City young urbanites and their potential impact on neurovascular unit dysfunction and the development of Alzheimer's disease. AB - Millions of urban children are chronically exposed to high concentrations of air pollutants, i.e., fine particulate matter (PM2.5) and ozone, associated with increased risk for Alzheimer's disease. Compared with children living with clear air those in Mexico City (MC) exhibit systemic, brain and intrathecal inflammation, low CSF Abeta42, breakdown of the BBB, attention and short-term memory deficits, prefrontal white matter hyperintensities, damage to epithelial and endothelial barriers, tight junction and neural autoantibodies, and Alzheimer and Parkinson's hallmarks. The prefrontal white matter is a target of air pollution. We examined by light and electron microscopy the prefrontal white matter of MC dogs (n: 15, age 3.17+/-0.74 years), children and teens (n: 34, age: 12.64+/-4.2 years) versus controls. Major findings in MC residents included leaking capillaries and small arterioles with extravascular lipids and erythrocytes, lipofuscin in pericytes, smooth muscle and endothelial cells (EC), thickening of cerebrovascular basement membranes with small deposits of amyloid, patchy absence of the perivascular glial sheet, enlarged Virchow-Robin spaces and nanosize particles (20-48nm) in EC, basement membranes, axons and dendrites. Tight junctions, a key component of the neurovascular unit (NVU) were abnormal in MC versus control dogs (chi(2)<0.0001), and white matter perivascular damage was significantly worse in MC dogs (p=0.002). The integrity of the NVU, an interactive network of vascular, glial and neuronal cells is compromised in MC young residents. Characterizing the early NVU damage and identifying biomarkers of neurovascular dysfunction may provide a fresh insight into Alzheimer pathogenesis and open opportunities for pediatric neuroprotection. PMID- 26829766 TI - CD4(+) T cell anergy prevents autoimmunity and generates regulatory T cell precursors. AB - The role of anergy, an acquired state of T cell functional unresponsiveness, in natural peripheral tolerance remains unclear. In this study, we found that anergy was selectively induced in fetal antigen-specific maternal CD4(+) T cells during pregnancy. A naturally occurring subpopulation of anergic polyclonal CD4(+) T cells, enriched for self antigen-specific T cell antigen receptors, was also present in healthy hosts. Neuropilin-1 expression in anergic conventional CD4(+) T cells was associated with hypomethylation of genes related to thymic regulatory T cells (Treg cells), and this correlated with their ability to differentiate into Foxp3(+) Treg cells that suppressed immunopathology. Thus, our data suggest that not only is anergy induction important in preventing autoimmunity but also it generates the precursors for peripheral Treg cell differentiation. PMID- 26829767 TI - SHARPIN controls regulatory T cells by negatively modulating the T cell antigen receptor complex. AB - SHARPIN forms a linear-ubiquitin-chain-assembly complex that promotes signaling via the transcription factor NF-kappaB. SHARPIN deficiency leads to progressive multi-organ inflammation and immune system malfunction, but how SHARPIN regulates T cell responses is unclear. Here we found that SHARPIN deficiency resulted in a substantial reduction in the number of and defective function of regulatory T cells (Treg cells). Transfer of SHARPIN-sufficient Treg cells into SHARPIN deficient mice considerably alleviated their systemic inflammation. SHARPIN deficient T cells displayed enhanced proximal signaling via the T cell antigen receptor (TCR) without an effect on the activation of NF-kappaB. SHARPIN conjugated with Lys63 (K63)-linked ubiquitin chains, which led to inhibition of the association of TCRzeta with the signaling kinase Zap70; this affected the generation of Treg cells. Our study therefore identifies a role for SHARPIN in TCR signaling whereby it maintains immunological homeostasis and tolerance by regulating Treg cells. PMID- 26829769 TI - Computational power and generative capacity of genetic systems. AB - Semiotic characteristics of genetic sequences are based on the general principles of linguistics formulated by Ferdinand de Saussure, such as the arbitrariness of sign and the linear nature of the signifier. Besides these semiotic features that are attributable to the basic structure of the genetic code, the principle of generativity of genetic language is important for understanding biological transformations. The problem of generativity in genetic systems arises to a possibility of different interpretations of genetic texts, and corresponds to what Alexander von Humboldt called "the infinite use of finite means". These interpretations appear in the individual development as the spatiotemporal sequences of realizations of different textual meanings, as well as the emergence of hyper-textual statements about the text itself, which underlies the process of biological evolution. These interpretations are accomplished at the level of the readout of genetic texts by the structures defined by Efim Liberman as "the molecular computer of cell", which includes DNA, RNA and the corresponding enzymes operating with molecular addresses. The molecular computer performs physically manifested mathematical operations and possesses both reading and writing capacities. Generativity paradoxically resides in the biological computational system as a possibility to incorporate meta-statements about the system, and thus establishes the internal capacity for its evolution. PMID- 26829768 TI - Glutamylation of the DNA sensor cGAS regulates its binding and synthase activity in antiviral immunity. AB - Cyclic GMP-AMP synthase (cGAS) senses cytosolic DNA during viral infection and catalyzes synthesis of the dinucleotide cGAMP, which activates the adaptor STING to initiate antiviral responses. Here we found that deficiency in the carboxypeptidase CCP5 or CCP6 led to susceptibility to DNA viruses. CCP5 and CCP6 were required for activation of the transcription factor IRF3 and interferons. Polyglutamylation of cGAS by the enzyme TTLL6 impeded its DNA-binding ability, whereas TTLL4-mediated monoglutamylation of cGAS blocked its synthase activity. Conversely, CCP6 removed the polyglutamylation of cGAS, whereas CCP5 hydrolyzed the monoglutamylation of cGAS, which together led to the activation of cGAS. Therefore, glutamylation and deglutamylation of cGAS tightly modulate immune responses to infection with DNA viruses. PMID- 26829770 TI - Human olfactory stem cells for injured facial nerve reconstruction in a rat model. AB - BACKGROUND: The purpose of this study was to show the efficacy of olfactory stem cells for injured facial nerve reconstruction in a rat model. METHODS: Olfactory stem cells were isolated from the olfactory mucosa of human participants. A 2-mm excision was performed on the right facial nerve of all rats. Reconstruction was performed with a conduit in group 1 (n = 9); a conduit and phosphate-buffered saline in group 2 (n = 9); and a conduit and labeled olfactory stem cell in group 3 (n = 9). Rats were followed for whisker movements and electroneuronography (ENoG) analyses. RESULTS: The whisker-movement scores for group 3 were significantly different from other groups (p < .001). ENoG showed that the amplitude values for group 3 were significantly different from group 1 and group 2 (p = .030; p < .001). Group 3 showed marked olfactory stem cell under a fluorescence microscope. CONCLUSION: This study suggests that olfactory stem cells may be used as a potent cellular therapy for accelerating the regeneration of peripheral nerve injuries. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2011-E2020, 2016. PMID- 26829771 TI - Characterization and Use of a Fiber Optic Sensor Based on PAH/SiO2 Film for Humidity Sensing in Ventilator Care Equipment. AB - OBJECTIVE: To develop a compact probe that can be used to monitor humidity in ventilator care equipment. A mesoporous film of alternate layers of Poly(allylamine hydrochloride) (PAH) and silica (SiO2) nanoparticles (bilayers), deposited onto an optical fibre was used. The sensing film behaves as a Fabry Perot cavity of low-finesse where the absorption of water vapour changes the optical thickness and produces a change in reflection proportional to humidity. METHODS: The mesoporous film was deposited upon the cleaved tip of an optical fibre using the layer-by-layer method. The sensor was calibrated in a bench model against a commercially available capacitive sensor. The sensitivity and response time were assessed in the range from 5 % relative humidity (RH) to 95%RH for different numbers of bilayers up to a maximum of nine. RESULTS: The sensitivity increases with the number of bilayers deposited; sensitivity of 2.28 mV/%RH was obtained for nine bilayers. The time constant of the response was 1.13 s +/- 0.30 s which is faster than the commercial device (measured as 158 s). After calibration, the optical fibre humidity sensor was utilised in a bench top study employing a mechanical ventilator. The fast response time enabled changes in humidity in individual breaths to be resolved. CONCLUSION: Optical fibre sensors have the potential to be used to monitor breath to breath humidity during ventilator care. SIGNIFICANCE: Control of humidity is an essential part of critical respiratory care and the developed sensor provides a sensitive, compact and fast method of humidity monitoring. PMID- 26829772 TI - Iterative Covariance-Based Removal of Time-Synchronous Artifacts: Application to Gastrointestinal Electrical Recordings. AB - OBJECTIVE: The aim of this study was to develop, validate, and apply a fully automated method for reducing large temporally synchronous artifacts present in electrical recordings made from the gastrointestinal (GI) serosa, which are problematic for properly assessing slow wave dynamics. Such artifacts routinely arise in experimental and clinical settings from motion, switching behavior of medical instruments, or electrode array manipulation. METHODS: A novel iterative Covariance-Based Reduction of Artifacts (COBRA) algorithm sequentially reduced artifact waveforms using an updating across-channel median as a noise template, scaled and subtracted from each channel based on their covariance. RESULTS: Application of COBRA substantially increased the signal-to-artifact ratio (12.8 +/- 2.5 dB), while minimally attenuating the energy of the underlying source signal by 7.9% on average ( -11.1 +/- 3.9 dB). CONCLUSION: COBRA was shown to be highly effective for aiding recovery and accurate marking of slow wave events (sensitivity = 0.90 +/- 0.04; positive-predictive value = 0.74 +/- 0.08) from large segments of in vivo porcine GI electrical mapping data that would otherwise be lost due to a broad range of contaminating artifact waveforms. SIGNIFICANCE: Strongly reducing artifacts with COBRA ultimately allowed for rapid production of accurate isochronal activation maps detailing the dynamics of slow wave propagation in the porcine intestine. Such mapping studies can help characterize differences between normal and dysrhythmic events, which have been associated with GI abnormalities, such as intestinal ischemia and gastroparesis. The COBRA method may be generally applicable for removing temporally synchronous artifacts in other biosignal processing domains. PMID- 26829773 TI - An Implantable Wireless Interstitial Pressure Sensor With Integrated Guyton Chamber: in vivo Study in Solid Tumors. AB - A wireless implantable interstitial fluid pressure (IFP) sensor with an integrated Guyton chamber is presented. This implantable device enables noninvasive and continuous measurements of IFP. The Guyton chamber allows for an accurate measurement of IFP without the interference from various cellular/tissue components. The sensor consists of a coil, an air chamber, a silicone membrane embedded with a nickel plate, and a Guyton chamber. The fabricated device is 3 mm in diameter and 1 mm in thickness. The sensor shows a linear response to the pressure with a sensitivity of 60 kHz/mmHg and a resolution of 1 mmHg. Experiments in human prostate cancer tumors grown in mice confirm the sensor's capability to operate in vivo and provide continuous wireless measurement of IFP, a surrogate parameter indicating the "window of opportunity" for delivering chemo and radio-therapeutic agents. PMID- 26829774 TI - Human Pose Estimation from Video and IMUs. AB - In this work, we present an approach to fuse video with sparse orientation data obtained from inertial sensors to improve and stabilize full-body human motion capture. Even though video data is a strong cue for motion analysis, tracking artifacts occur frequently due to ambiguities in the images, rapid motions, occlusions or noise. As a complementary data source, inertial sensors allow for accurate estimation of limb orientations even under fast motions. However, accurate position information cannot be obtained in continuous operation. Therefore, we propose a hybrid tracker that combines video with a small number of inertial units to compensate for the drawbacks of each sensor type: on the one hand, we obtain drift-free and accurate position information from video data and, on the other hand, we obtain accurate limb orientations and good performance under fast motions from inertial sensors. In several experiments we demonstrate the increased performance and stability of our human motion tracker. PMID- 26829775 TI - Learning to Diffuse: A New Perspective to Design PDEs for Visual Analysis. AB - Partial differential equations (PDEs) have been used to formulate image processing for several decades. Generally, a PDE system consists of two components: the governing equation and the boundary condition. In most previous work, both of them are generally designed by people using mathematical skills. However, in real world visual analysis tasks, such predefined and fixed-form PDEs may not be able to describe the complex structure of the visual data. More importantly, it is hard to incorporate the labeling information and the discriminative distribution priors into these PDEs. To address above issues, we propose a new PDE framework, named learning to diffuse (LTD), to adaptively design the governing equation and the boundary condition of a diffusion PDE system for various vision tasks on different types of visual data. To our best knowledge, the problems considered in this paper (i.e., saliency detection and object tracking) have never been addressed by PDE models before. Experimental results on various challenging benchmark databases show the superiority of LTD against existing state-of-the-art methods for all the tested visual analysis tasks. PMID- 26829776 TI - Comments on the "Kinship Face in the Wild" Data Sets. AB - The Kinship Face in the Wild data sets, recently published in TPAMI, are currently used as a benchmark for the evaluation of kinship verification algorithms. We recommend that these data sets are no longer used in kinship verification research unless there is a compelling reason that takes into account the nature of the images. We note that most of the image kinship pairs are cropped from the same photographs. Exploiting this cropping information, competitive but biased performance can be obtained using a simple scoring approach, taking only into account the nature of the image pairs rather than any features about kin information. To illustrate our motives, we provide classification results utilizing a simple scoring method based on the image similarity of both images of a kinship pair. Using simply the distance of the chrominance averages of the images in the Lab color space without any training or using any specific kin features, we achieve performance comparable to state-of the-art methods. We provide the source code to prove the validity of our claims and ensure the repeatability of our experiments. PMID- 26829777 TI - Person Re-Identification by Discriminative Selection in Video Ranking. AB - Current person re-identification (ReID) methods typically rely on single-frame imagery features, whilst ignoring space-time information from image sequences often available in the practical surveillance scenarios. Single-frame (single shot) based visual appearance matching is inherently limited for person ReID in public spaces due to the challenging visual ambiguity and uncertainty arising from non-overlapping camera views where viewing condition changes can cause significant people appearance variations. In this work, we present a novel model to automatically select the most discriminative video fragments from noisy/incomplete image sequences of people from which reliable space-time and appearance features can be computed, whilst simultaneously learning a video ranking function for person ReID. Using the PRID 2011, iLIDS-VID, and HDA+ image sequence datasets, we extensively conducted comparative evaluations to demonstrate the advantages of the proposed model over contemporary gait recognition, holistic image sequence matching and state-of-the-art single-/multi shot ReID methods. PMID- 26829779 TI - Surface Regions of Interest for Viewpoint Selection. AB - While the detection of the interesting regions in images has been extensively studied, relatively few papers have addressed surfaces. This paper proposes an algorithm for detecting the regions of interest of surfaces. It looks for regions that are distinct both locally and globally and accounts for the distance to the foci of attention. It is also shown how this algorithm can be adopted to saliency detection in point clouds. Many applications can utilize these regions. In this paper we explore one such application-viewpoint selection. The most informative views are those that collectively provide the most descriptive presentation of the surface. We show that our results compete favorably with the state-of-the-art results. PMID- 26829782 TI - 3D Reconstruction of Human Laryngeal Dynamics Based on Endoscopic High-Speed Recordings. AB - Standard laryngoscopic imaging techniques provide only limited two-dimensional insights into the vocal fold vibrations not taking the vertical component into account. However, previous experiments have shown a significant vertical component in the vibration of the vocal folds. We present a 3D reconstruction of the entire superior vocal fold surface from 2D high-speed videoendoscopy via stereo triangulation. In a typical camera-laser set-up the structured laser light pattern is projected on the vocal folds and captured at 4000 fps. The measuring device is suitable for in vivo application since the external dimensions of the miniaturized set-up barely exceed the size of a standard rigid laryngoscope. We provide a conservative estimate on the resulting resolution based on the hardware components and point out the possibilities and limitations of the miniaturized camera-laser set-up. In addition to the 3D vocal fold surface, we extended previous approaches with a G2-continuous model of the vocal fold edge. The clinical applicability was successfully established by the reconstruction of visual data acquired from 2D in vivo high-speed recordings of a female and a male subject. We present extracted dynamic parameters like maximum amplitude and velocity in the vertical direction. The additional vertical component reveals deeper insights into the vibratory dynamics of the vocal folds by means of a non invasive method. The successful miniaturization allows for in vivo application giving access to the most realistic model available and hence enables a comprehensive understanding of the human phonation process. PMID- 26829783 TI - Multiple-Instance Learning for Anomaly Detection in Digital Mammography. AB - This paper describes a computer-aided detection and diagnosis system for breast cancer, the most common form of cancer among women, using mammography. The system relies on the Multiple-Instance Learning (MIL) paradigm, which has proven useful for medical decision support in previous works from our team. In the proposed framework, breasts are first partitioned adaptively into regions. Then, features derived from the detection of lesions (masses and microcalcifications) as well as textural features, are extracted from each region and combined in order to classify mammography examinations as "normal" or "abnormal". Whenever an abnormal examination record is detected, the regions that induced that automated diagnosis can be highlighted. Two strategies are evaluated to define this anomaly detector. In a first scenario, manual segmentations of lesions are used to train an SVM that assigns an anomaly index to each region; local anomaly indices are then combined into a global anomaly index. In a second scenario, the local and global anomaly detectors are trained simultaneously, without manual segmentations, using various MIL algorithms (DD, APR, mi-SVM, MI-SVM and MILBoost). Experiments on the DDSM dataset show that the second approach, which is only weakly-supervised, surprisingly outperforms the first approach, even though it is strongly supervised. This suggests that anomaly detectors can be advantageously trained on large medical image archives, without the need for manual segmentation. PMID- 26829784 TI - Deformable Graph Model for Tracking Epithelial Cell Sheets in Fluorescence Microscopy. AB - We propose a novel method for tracking cells that are connected through a visible network of membrane junctions. Tissues of this form are common in epithelial cell sheets and resemble planar graphs where each face corresponds to a cell. We leverage this structure and develop a method to track the entire tissue as a deformable graph. This coupled model in which vertices inform the optimal placement of edges and vice versa captures global relationships between tissue components and leads to accurate and robust cell tracking. We compare the performance of our method with that of four reference tracking algorithms on four data sets that present unique tracking challenges. Our method exhibits consistently superior performance in tracking all cells accurately over all image frames, and is robust over a wide range of image intensity and cell shape profiles. This may be an important tool for characterizing tissues of this type especially in the field of developmental biology where automated cell analysis can help elucidate the mechanisms behind controlled cell-shape changes. PMID- 26829785 TI - A CNN Regression Approach for Real-Time 2D/3D Registration. AB - In this paper, we present a Convolutional Neural Network (CNN) regression approach to address the two major limitations of existing intensity-based 2-D/3-D registration technology: 1) slow computation and 2) small capture range. Different from optimization-based methods, which iteratively optimize the transformation parameters over a scalar-valued metric function representing the quality of the registration, the proposed method exploits the information embedded in the appearances of the digitally reconstructed radiograph and X-ray images, and employs CNN regressors to directly estimate the transformation parameters. An automatic feature extraction step is introduced to calculate 3-D pose-indexed features that are sensitive to the variables to be regressed while robust to other factors. The CNN regressors are then trained for local zones and applied in a hierarchical manner to break down the complex regression task into multiple simpler sub-tasks that can be learned separately. Weight sharing is furthermore employed in the CNN regression model to reduce the memory footprint. The proposed approach has been quantitatively evaluated on 3 potential clinical applications, demonstrating its significant advantage in providing highly accurate real-time 2-D/3-D registration with a significantly enlarged capture range when compared to intensity-based methods. PMID- 26829786 TI - White Matter MS-Lesion Segmentation Using a Geometric Brain Model. AB - Brain magnetic resonance imaging (MRI) in patients with Multiple Sclerosis (MS) shows regions of signal abnormalities, named plaques or lesions. The spatial lesion distribution plays a major role for MS diagnosis. In this paper we present a 3D MS-lesion segmentation method based on an adaptive geometric brain model. We model the topological properties of the lesions and brain tissues in order to constrain the lesion segmentation to the white matter. As a result, the method is independent of an MRI atlas. We tested our method on the MICCAI MS grand challenge proposed in 2008 and achieved competitive results. In addition, we used an in-house dataset of 15 MS patients, for which we achieved best results in most distances in comparison to atlas based methods. Besides classical segmentation distances, we motivate and formulate a new distance to evaluate the quality of the lesion segmentation, while being robust with respect to minor inconsistencies at the boundary level of the ground truth annotation. PMID- 26829787 TI - A New High-Temperature Ultrasonic Transducer for Continuous Inspection. AB - A novel design of piezoelectric ultrasonic transducer is introduced, suitable for operation at temperatures of up to 700 degrees C-800 degrees C. Lithium niobate single crystal is chosen as the piezoelectric element primarily due to the high Curie temperature of 1200 degrees C. A backing element based on a porous ceramic is designed for which the pore volume fraction and average pore diameter in the ceramic matrix can be controlled in the manufacturing process; this enables the acoustic impedance and attenuation to be selected to match their optimal values as predicted by a one-dimensional transducer model of the entire transducer. Porous zirconia is selected as the ceramic matrix material of the backing element to obtain an ultrasonic signal with center frequency of 2.7-3 MHz, and 3-dB bandwidth of 90%-95% at the targeted operating temperature. Acoustic coupling of the piezocrystal to the backing element and matching layer is investigated using commercially available high-temperature adhesives and brazing alloys. The performance of the transducer as a function of temperature is studied. Stable bonding and clear signals were obtained using an aluminum brazing alloy as the bonding agent. PMID- 26829788 TI - Oscillator PM Noise Reduction From Correlated AM Noise. AB - We demonstrate a novel technique for reducing the phase modulation (PM) noise of an oscillator in a steady-state condition as well as under vibration. It utilizes correlation between PM noise and amplitude modulation (AM) noise that can originate from the oscillator's loop components. A control voltage proportional to the correlated AM noise is generated and utilized in a feedforward architecture to correct for the steady state as well as the vibration-induced PM noise. An improvement of almost 10-15 dB in PM noise is observed over one decade of offset frequencies for a 635-MHz quartz-MEMS oscillator. This corresponds to more than a factor of five reductions in vibration sensitivity. PMID- 26829789 TI - Geometry-Aware Neighborhood Search for Learning Local Models for Image Superresolution. AB - Local learning of sparse image models has proved to be very effective to solve inverse problems in many computer vision applications. To learn such models, the data samples are often clustered using the K-means algorithm with the Euclidean distance as a dissimilarity metric. However, the Euclidean distance may not always be a good dissimilarity measure for comparing data samples lying on a manifold. In this paper, we propose two algorithms for determining a local subset of training samples from which a good local model can be computed for reconstructing a given input test sample, where we consider the underlying geometry of the data. The first algorithm, called adaptive geometry-driven nearest neighbor search (AGNN), is an adaptive scheme, which can be seen as an out-of-sample extension of the replicator graph clustering method for local model learning. The second method, called geometry-driven overlapping clusters (GOCs), is a less complex nonadaptive alternative for training subset selection. The proposed AGNN and GOC methods are evaluated in image superresolution and shown to outperform spectral clustering, soft clustering, and geodesic distance-based subset selection in most settings. PMID- 26829790 TI - Probability Distribution Estimation for Autoregressive Pixel-Predictive Image Coding. AB - Pixelwise linear prediction using backward-adaptive least-squares or weighted least-squares estimation of prediction coefficients is currently among the state of-the-art methods for lossless image compression. While current research is focused on mean intensity prediction of the pixel to be transmitted, best compression requires occurrence probability estimates for all possible intensity values. Apart from common heuristic approaches, we show how prediction error variance estimates can be derived from the (weighted) least-squares training region and how a complete probability distribution can be built based on an autoregressive image model. The analysis of image stationarity properties further allows deriving a novel formula for weight computation in weighted least-squares proofing and generalizing ad hoc equations from the literature. For sparse intensity distributions in non-natural images, a modified image model is presented. Evaluations were done in the newly developed C++ framework volumetric, artificial, and natural image lossless coder (Vanilc), which can compress a wide range of images, including 16-bit medical 3D volumes or multichannel data. A comparison with several of the best available lossless image codecs proofs that the method can achieve very competitive compression ratios. In terms of reproducible research, the source code of Vanilc has been made public. PMID- 26829791 TI - Median Robust Extended Local Binary Pattern for Texture Classification. AB - Local binary patterns (LBP) are considered among the most computationally efficient high-performance texture features. However, the LBP method is very sensitive to image noise and is unable to capture macrostructure information. To best address these disadvantages, in this paper, we introduce a novel descriptor for texture classification, the median robust extended LBP (MRELBP). Different from the traditional LBP and many LBP variants, MRELBP compares regional image medians rather than raw image intensities. A multiscale LBP type descriptor is computed by efficiently comparing image medians over a novel sampling scheme, which can capture both microstructure and macrostructure texture information. A comprehensive evaluation on benchmark data sets reveals MRELBP's high performance robust to gray scale variations, rotation changes and noise-but at a low computational cost. MRELBP produces the best classification scores of 99.82%, 99.38%, and 99.77% on three popular Outex test suites. More importantly, MRELBP is shown to be highly robust to image noise, including Gaussian noise, Gaussian blur, salt-and-pepper noise, and random pixel corruption. PMID- 26829792 TI - Learning a Combined Model of Visual Saliency for Fixation Prediction. AB - A large number of saliency models, each based on a different hypothesis, have been proposed over the past 20 years. In practice, while subscribing to one hypothesis or computational principle makes a model that performs well on some types of images, it hinders the general performance of a model on arbitrary images and large-scale data sets. One natural approach to improve overall saliency detection accuracy would then be fusing different types of models. In this paper, inspired by the success of late-fusion strategies in semantic analysis and multi-modal biometrics, we propose to fuse the state-of-the-art saliency models at the score level in a para-boosting learning fashion. First, saliency maps generated by several models are used as confidence scores. Then, these scores are fed into our para-boosting learner (i.e., support vector machine, adaptive boosting, or probability density estimator) to generate the final saliency map. In order to explore the strength of para-boosting learners, traditional transformation-based fusion strategies, such as Sum, Min, and Max, are also explored and compared in this paper. To further reduce the computation cost of fusing too many models, only a few of them are considered in the next step. Experimental results show that score-level fusion outperforms each individual model and can further reduce the performance gap between the current models and the human inter-observer model. PMID- 26829793 TI - The Use of Empirical Mode Decomposition-Based Algorithm and Inertial Measurement Units to Auto-Detect Daily Living Activities of Healthy Adults. AB - he use of inertial measurement units (IMUs) in motion analysis for clinical purpose is relatively recent. However, the use of such system in free environment remains sparse. This is in part due the lack of robust algorithms to handle large volumes of data for performance evaluation and patient diagnosis. The present work examines the ability of using Empirical Mode Decomposition and discrete-time detection of events to automatically detect and segment tasks associated with activities of daily living (ADL) using IMUs. Seven healthy older adults (73+/- 4 years old) performed ADL tasks in a simulated apartment during trials of different durations (3, 4, and 5-min). They wore a suit (Synertial-IGS180) comprised of 17-IMUs positioned strategically on body segments to capture full body motion. After a systematic process examining time series of each sensor, it was determined that 6-IMUs were sufficient to detect the 9 tasks at hand (such as walking, sit to stand, stand to sit, reaching to the ground to pick or to put down objects on the floor, step an obstacle and turning). The proposed method automatically identified the proper set of template waveforms associated to ADL tasks based on kinematic data acquired from the selected IMUs. The ground truth on timing of tasks was established by visual segmentation of recordings using the system's software. Despite the variation in the occurrences of the performed tasks (freely moving), the proposed algorithm exhibited high global accuracy under unscripted conditions of motion, for both Se. and Sp. of 97% (Nevents=1999), using a few features and without learning process. This work will eventually allow for the assessment of mobility performance within the segmented signals; specifically how well the person is moving in his/her environment. PMID- 26829794 TI - State of the Art and Future Directions for Lower Limb Robotic Exoskeletons. AB - Research on robotic exoskeletons has rapidly expanded over the previous decade. Advances in robotic hardware and energy supplies have enabled viable prototypes for human testing. This review paper describes current lower limb robotic exoskeletons, with specific regard to common trends in the field. The preponderance of published literature lacks rigorous quantitative evaluations of exoskeleton performance, making it difficult to determine the disadvantages and drawbacks of many of the devices. We analyzed common approaches in exoskeleton design and the convergence, or lack thereof, with certain technologies. We focused on actuators, sensors, energy sources, materials, and control strategies. One of the largest hurdles to be overcome in exoskeleton research is the user interface and control. More intuitive and flexible user interfaces are needed to increase the success of robotic exoskeletons. In the last section, we discuss promising future solutions to the major hurdles in exoskeleton control. A number of emerging technologies could deliver substantial advantages to existing and future exoskeleton designs. We conclude with a listing of the advantages and disadvantages of the emerging technologies and discuss possible futures for the field. PMID- 26829795 TI - Children With Dystonia Can Learn a Novel Motor Skill: Strategies That are Tolerant to High Variability. AB - Children with dystonia are characterized by highly variable and seemingly uncontrolled movements. An important question for any rehabilitative effort is whether these children can learn and improve their performance. This study compared children with dystonia due to cerebral palsy, typically developing children, and healthy adults in their ability to acquire a novel sensorimotor skill. Using a virtual setup, subjects threw a virtual ball tethered to a post to hit a virtual target. Multiple combinations of release angle and velocity of the arm at ball release could achieve a target hit-the task was redundant and afforded solutions with different sensitivity to variability. Subjects performed 200 trials for two target locations that presented different types of redundancy. We hypothesized that children with dystonia develop strategies that are tolerant to their high variability. Estimating this variability highlighted the insufficiency of traditional outcome measures. Therefore, additional analyses of data distributions and of ball release timing were applied. Results showed that: 1) children with dystonia reduced their performance error despite their high variability; 2) this improvement was brought about by finding error-tolerant solutions; and 3) they generated arm trajectories that created time windows for ball release that were tolerant to timing variability. While reduced in magnitude, the performance improvements in children with dystonia paralleled those in healthy children and adults. These findings demonstrate that children with dystonia are able to adapt their behavior to their high variability, an important basis for any rehabilitative intervention. PMID- 26829796 TI - Design and Evaluation of a Soft and Wearable Robotic Glove for Hand Rehabilitation. AB - In the modern world, due to an increased aging population, hand disability is becoming increasingly common. The prevalence of conditions such as stroke is placing an ever-growing burden on the limited fiscal resources of health care providers and the capacity of their physical therapy staff. As a solution, this paper presents a novel design for a wearable and adaptive glove for patients so that they can practice rehabilitative activities at home, reducing the workload for therapists and increasing the patient's independence. As an initial evaluation of the design's feasibility the prototype was subjected to motion analysis to compare its performance with the hand in an assessment of grasping patterns of a selection of blocks and spheres. The outcomes of this paper suggest that the theory of design has validity and may lead to a system that could be successful in the treatment of stroke patients to guide them through finger flexion and extension, which could enable them to gain more control and confidence in interacting with the world around them. PMID- 26829797 TI - Quantifying Spasticity With Limited Swinging Cycles Using Pendulum Test Based on Phase Amplitude Coupling. AB - Parameters derived from the goniometer measures in the Pendulum test are insufficient in describing the function of abnormal muscle activity in the spasticity. To explore a quantitative evaluation of muscle activation-movement interaction, we propose a novel index based on phase amplitude coupling (PAC) analysis with the consideration of the relations between movement and surface electromyography (SEMG) activity among 22 hemiplegic stroke patients. To take off trend and noise, we use the empirical mode decomposition (EMD) to obtain intrinsic mode functions (IMFs) of the angular velocity due to its superior decomposing ability in nonlinear oscillations. Shannon entropy based on angular velocity (phase)-envelope of EMG (amplitude) distribution was calculated to demonstrate characteristics of the coupling between SEMG activity and joint movement. We also compare our results with those from traditional methods such as the normalized relaxation index derived from the Pendulum test and the mean root mean square (RMS) of the SEMG signals in the study. Our results show effective discrimination ability between spastic and nonaffected limbs using our method . This study indicates the feasibility of using the novel indices based on the PAC in evaluation the spasticity among the hemiplegic stroke patients with less than three swinging cycles. PMID- 26829798 TI - Swing Phase Control of Semi-Active Prosthetic Knee Using Neural Network Predictive Control With Particle Swarm Optimization. AB - In recent years, intelligent prosthetic knees have been developed that enable amputees to walk as normally as possible when compared to healthy subjects. Although semi-active prosthetic knees utilizing magnetorheological (MR) dampers offer several advantages, they lack the ability to generate active force that is required during some states of a normal gait cycle. This prevents semi-active knees from achieving the same level of performance as active devices. In this work, a new control algorithm for a semi-active prosthetic knee during the swing phase is proposed to reduce this gap. The controller uses neural network predictive control and particle swarm optimization to calculate suitable command signals. Simulation results using a double pendulum model show that the generated knee trajectory of the proposed controller is more similar to the normal gait than previous open-loop controllers at various ambulation speeds. Moreover, the investigation shows that the algorithm can be calculated in real time by an embedded system, allowing for easy implementation on real prosthetic knees. PMID- 26829800 TI - In-Body Network Biomedical Applications: From Modeling to Experimentation. AB - Innovative diagnostic approaches and therapies are more and more based on the use of injections or oral delivery of nanoparticle sized substances. For a better understanding of the overall phenomena, aiming to facilitate a safe application at large scale, the development of accurate models and analysis techniques are required. These techniques take into consideration different aspects of the overall process: accurate numerical modeling of the different phases of the nanoparticles in the body, and knowledge of the local environment, that can be varying very fast within a short-range in the body itself. Such aspects should be taken into account to correctly predict the amount of drug and its timely release for the specific disease. Deep and accurate analysis of the interaction between the nanoparticles and the biological fluid where the nanoparticles are immersed is mandatory for an efficient correlation of all these aspects. Because of their biocompatibility, in this paper, we focus our attention on systems of Titanium (Ti), and its oxide (e.g., TiO2), given their specific features in terms of density, lack of cytotoxic effects, etc. Specifically, we present the study and design of an in-body system by characterizing each of the emission, diffusion, and reception processes with a proper realistic model. The theoretical investigation is further supported by experimental study of the morphology and other important characteristics (e.g., the pH of the particles, and thermal stability) of TiO2 systems when immersed in a Ringer solution, in order to derive important information related to their potential toxicity inside the human body. PMID- 26829799 TI - Scale of Carbon Nanomaterials Affects Neural Outgrowth and Adhesion. AB - Carbon nanomaterials have become increasingly popular microelectrode materials for neuroscience applications. Here we study how the scale of carbon nanotubes and carbon nanofibers affect neural viability, outgrowth, and adhesion. Carbon nanotubes were deposited on glass coverslips via a layer-by-layer method with polyethylenimine (PEI). Carbonized nanofibers were fabricated by electrospinning SU-8 and pyrolyzing the nanofiber depositions. Additional substrates tested were carbonized and SU-8 thin films and SU-8 nanofibers. Surfaces were O2-plasma treated, coated with varying concentrations of PEI, seeded with E18 rat cortical cells, and examined at 3, 4, and 7 days in vitro (DIV). Neural adhesion was examined at 4 DIV utilizing a parallel plate flow chamber. At 3 DIV, neural viability was lower on the nanofiber and thin film depositions treated with higher PEI concentrations which corresponded with significantly higher zeta potentials (surface charge); this significance was drastically higher on the nanofibers suggesting that the nanostructure may collect more PEI molecules, causing increased toxicity. At 7 DIV, significantly higher neurite outgrowth was observed on SU-8 nanofiber substrates with nanofibers a significant fraction of a neuron's size. No differences were detected for carbonized nanofibers or carbon nanotubes. Both carbonized and SU-8 nanofibers had significantly higher cellular adhesion post-flow in comparison to controls whereas the carbon nanotubes were statistically similar to control substrates. These data suggest a neural cell preference for larger-scale nanomaterials with specific surface treatments. These characteristics could be taken advantage of in the future design and fabrication of neural microelectrodes. PMID- 26829801 TI - Identifying Disease Associated miRNAs Based on Protein Domains. AB - MicroRNAs (miRNAs) are a class of small endogenous non-coding genes, acting as regulators in the post-transcriptional processes. Recently, the miRNAs are found to be widely involved in different types of diseases. Therefore, the identification of disease associated miRNAs can help understand the mechanisms that underlie the disease and identify new biomarkers. However, it is not easy to identify the miRNAs related to diseases due to its extensive involvements in various biological processes. In this work, we present a new approach to identify disease associated miRNAs based on domains, the functional and structural blocks of proteins. The results on real datasets demonstrate that our method can effectively identify disease related miRNAs with high precision. PMID- 26829803 TI - Magnetic Surgical Instruments for Robotic Abdominal Surgery. AB - This review looks at the implementation of magnetic-based approaches in surgical instruments for abdominal surgeries. As abdominal surgical techniques advance toward minimizing surgical trauma, surgical instruments are enhanced to support such an objective through the exploration of magnetic-based systems. With this design approach, surgical devices are given the capabilities to be fully inserted intraabdominally to achieve access to all abdominal quadrants, without the conventional rigid link connection with the external unit. The variety of intraabdominal surgical devices are anchored, guided, and actuated by external units, with power and torque transmitted across the abdominal wall through magnetic linkage. This addresses many constraints encountered by conventional laparoscopic tools, such as loss of triangulation, fulcrum effect, and loss/lack of dexterity for surgical tasks. Design requirements of clinical considerations to aid the successful development of magnetic surgical instruments, are also discussed. PMID- 26829802 TI - An Annotation Agnostic Algorithm for Detecting Nascent RNA Transcripts in GRO Seq. AB - We present a fast and simple algorithm to detect nascent RNA transcription in global nuclear run-on sequencing (GRO-seq). GRO-seq is a relatively new protocol that captures nascent transcripts from actively engaged polymerase, providing a direct read-out on bona fide transcription. Most traditional assays, such as RNA seq, measure steady state RNA levels which are affected by transcription, post transcriptional processing, and RNA stability. GRO-seq data, however, presents unique analysis challenges that are only beginning to be addressed. Here, we describe a new algorithm, Fast Read Stitcher (FStitch), that takes advantage of two popular machine-learning techniques, hidden Markov models and logistic regression, to classify which regions of the genome are transcribed. Given a small user-defined training set, our algorithm is accurate, robust to varying read depth, annotation agnostic, and fast. Analysis of GRO-seq data without a priori need for annotation uncovers surprising new insights into several aspects of the transcription process. PMID- 26829804 TI - Single-Grasp Object Classification and Feature Extraction with Simple Robot Hands and Tactile Sensors. AB - Classical robotic approaches to tactile object identification often involve rigid mechanical grippers, dense sensor arrays, and exploratory procedures (EPs). Though EPs are a natural method for humans to acquire object information, evidence also exists for meaningful tactile property inference from brief, non exploratory motions (a 'haptic glance'). In this work, we implement tactile object identification and feature extraction techniques on data acquired during a single, unplanned grasp with a simple, underactuated robot hand equipped with inexpensive barometric pressure sensors. Our methodology utilizes two cooperating schemes based on an advanced machine learning technique (random forests) and parametric methods that estimate object properties. The available data is limited to actuator positions (one per two link finger) and force sensors values (eight per finger). The schemes are able to work both independently and collaboratively, depending on the task scenario. When collaborating, the results of each method contribute to the other, improving the overall result in a synergistic fashion. Unlike prior work, the proposed approach does not require object exploration, re grasping, grasp-release, or force modulation and works for arbitrary object start positions and orientations. Due to these factors, the technique may be integrated into practical robotic grasping scenarios without adding time or manipulation overheads. PMID- 26829806 TI - Manifold-Based Reinforcement Learning via Locally Linear Reconstruction. AB - Feature representation is critical not only for pattern recognition tasks but also for reinforcement learning (RL) methods to solve learning control problems under uncertainties. In this paper, a manifold-based RL approach using the principle of locally linear reconstruction (LLR) is proposed for Markov decision processes with large or continuous state spaces. In the proposed approach, an LLR based feature learning scheme is developed for value function approximation in RL, where a set of smooth feature vectors is generated by preserving the local approximation properties of neighboring points in the original state space. By using the proposed feature learning scheme, an LLR-based approximate policy iteration (API) algorithm is designed for learning control problems with large or continuous state spaces. The relationship between the value approximation error of a new data point and the estimated values of its nearest neighbors is analyzed. In order to compare different feature representation and learning approaches for RL, a comprehensive simulation and experimental study was conducted on three benchmark learning control problems. It is illustrated that under a wide range of parameter settings, the LLR-based API algorithm can obtain better learning control performance than the previous API methods with different feature representation schemes. PMID- 26829805 TI - Simulations of a Vibrissa Slipping along a Straight Edge and an Analysis of Frictional Effects during Whisking. AB - During tactile exploration, rats sweep their whiskers against objects in a motion called whisking. Here, we investigate how a whisker slips along an object's edge and how friction affects the resulting tactile signals. First, a frictionless model is developed to simulate whisker slip along a straight edge and compared with a previous model that incorporates friction but cannot simulate slip. Results of both models are compared to behavioral data obtained as a rat whisked against a smooth, stainless steel peg. As expected, the frictionless model predicts larger magnitudes of vertical slip than observed experimentally. The frictionless model also predicts forces and moments at the whisker base that are smaller and have a different direction than those predicted by the model with friction. Estimates for the friction coefficient yielded values near 0.48 (whisker/stainless steel). The present work provides the first assessments of the effects of friction on the mechanical signals received by the follicle during active whisking. It also demonstrates a proof-of-principle approach for reducing whisker tracking requirements during experiments and demonstrates the feasibility of simulating a full array of vibrissae whisking against a peg. PMID- 26829807 TI - Machine Learning Capabilities of a Simulated Cerebellum. AB - This paper describes the learning and control capabilities of a biologically constrained bottom-up model of the mammalian cerebellum. Results are presented from six tasks: 1) eyelid conditioning; 2) pendulum balancing; 3) proportional integral-derivative control; 4) robot balancing; 5) pattern recognition; and 6) MNIST handwritten digit recognition. These tasks span several paradigms of machine learning, including supervised learning, reinforcement learning, control, and pattern recognition. Results over these six domains indicate that the cerebellar simulation is capable of robustly identifying static input patterns even when randomized across the sensory apparatus. This capability allows the simulated cerebellum to perform several different supervised learning and control tasks. On the other hand, both reinforcement learning and temporal pattern recognition prove problematic due to the delayed nature of error signals and the simulator's inability to solve the credit assignment problem. These results are consistent with previous findings which hypothesize that in the human brain, the basal ganglia is responsible for reinforcement learning, while the cerebellum handles supervised learning. PMID- 26829808 TI - A Maximum Entropy Framework for Semisupervised and Active Learning With Unknown and Label-Scarce Classes. AB - We investigate semisupervised learning (SL) and pool-based active learning (AL) of a classifier for domains with label-scarce (LS) and unknown categories, i.e., defined categories for which there are initially no labeled examples. This scenario manifests, e.g., when a category is rare, or expensive to label. There are several learning issues when there are unknown categories: 1) it is a priori unknown which subset of (possibly many) measured features are needed to discriminate unknown from common classes and 2) label scarcity suggests that overtraining is a concern. Our classifier exploits the inductive bias that an unknown class consists of the subset of the unlabeled pool's samples that are atypical (relative to the common classes) with respect to certain key (albeit a priori unknown) features and feature interactions. Accordingly, we treat negative log- p -values on raw features as nonnegatively weighted derived feature inputs to our class posterior, with zero weights identifying irrelevant features. Through a hierarchical class posterior, our model accommodates multiple common classes, multiple LS classes, and unknown classes. For learning, we propose a novel semisupervised objective customized for the LS/unknown category scenarios. While several works minimize class decision uncertainty on unlabeled samples, we instead preserve this uncertainty [maximum entropy (maxEnt)] to avoid overtraining. Our experiments on a variety of UCI Machine learning (ML) domains show: 1) the use of p -value features coupled with weight constraints leads to sparse solutions and gives significant improvement over the use of raw features and 2) for LS SL and AL, unlabeled samples are helpful, and should be used to preserve decision uncertainty (maxEnt), rather than to minimize it, especially during the early stages of AL. Our AL system, leveraging a novel sample-selection scheme, discovers unknown classes and discriminates LS classes from common ones, with sparing use of oracle labeling. PMID- 26829809 TI - Identification of Boolean Networks Using Premined Network Topology Information. AB - This brief aims to reduce the data requirement for the identification of Boolean networks (BNs) by using the premined network topology information. First, a matching table is created and used for sifting the true from the false dependences among the nodes in the BNs. Then, a dynamic extension to matching table is developed to enable the dynamic locating of matching pairs to start as soon as possible. Next, based on the pseudocommutative property of the semitensor product, a position-transform mining is carried out to further improve data utilization. Combining the above, the topology of the BNs can be premined for the subsequent identification. Examples are given to illustrate the efficiency of reducing the data requirement. Some excellent features, such as the online and parallel processing ability, are also demonstrated. PMID- 26829810 TI - Cross-Modality Feature Learning Through Generic Hierarchical Hyperlingual-Words. AB - Recognizing facial images captured under visible light has long been discussed in the past decades. However, there are many impact factors that hinder its successful application in real-world, e.g., illumination, pose variations. Recent work has concentrated on different spectrals, i.e., near infrared, that can only be perceived by specifically designed device to avoid the illumination problem. However, this inevitably introduces a new problem, namely, cross-modality classification. In brief, images registered in the system are in one modality, while images that captured momentarily used as the tests are in another modality. In addition, there could be many within-modality variations-pose and expression leading to a more complicated problem for the researchers. To address this problem, we propose a novel framework called hierarchical hyperlingual-words (Hwords) in this paper. First, we design a novel structure, called generic Hwords, to capture the high-level semantics across different modalities and within each modality in weakly supervised fashion, meaning only modality pair and variations information are needed in the training. Second, to improve the discriminative power of Hwords, we propose a novel distance metric through the hierarchical structure of Hwords. Extensive experiments on multimodality face databases demonstrate the superiority of our method compared with the state-of the-art works on face recognition tasks subject to pose and expression variations. PMID- 26829811 TI - Movement Path Tortuosity in Free Ambulation: Relationships to Age and Brain Disease. AB - Ambulation is defined by duration, distance traversed, number and size of directional changes, and the interval separating successive movement episodes; more complex measures of ambulation can be created by aggregating these features. This review article of published findings defines random changes in direction during movement as "movement path tortuosity" and relates tortuosity to the understanding of cognitive impairments of persons of all ages. Path tortuosity is quantified by subjecting tracking data to fractal analysis, specifically Fractal Dimension (Fractal D), which ranges from a value of 1 when the movement path is perfectly straight to a value of 2 when the movement path is random, resembling the "drunkard's walk." The review elucidates the mathematical assumptions underlying Fractal D, its use in the analysis of movements of free ranging animals, and its application to the study of cognitive impairment and the prediction of falls in older adults. We conclude Fractal D offers a reliable, valid, sensitive, and easily interpreted real-time longitudinal measure of unrestricted movement path tortuosity unaffected by mobility aid use. PMID- 26829812 TI - Rate and Distortion Optimization for Reversible Data Hiding Using Multiple Histogram Shifting. AB - Histogram shifting (HS) embedding as a typical reversible data hiding scheme is widely investigated due to its high quality of stego-image. For HS-based embedding, the selected side information, i.e., peak and zero bins, usually greatly affects the rate and distortion performance of the stego-image. Due to the massive solution space and burden in distortion computation, conventional HS based schemes utilize some empirical criterion to determine those side information, which generally could not lead to a globally optimal solution for reversible embedding. In this paper, based on the developed rate and distortion model, the problem of HS-based multiple embedding is formulated as the one of rate and distortion optimization. Two key propositions are then derived to facilitate the fast computation of distortion due to multiple shifting and narrow down the solution space, respectively. Finally, an evolutionary optimization algorithm, i.e., genetic algorithm is employed to search the nearly optimal zero and peak bins. For a given data payload, the proposed scheme could not only adaptively determine the proper number of peak and zero bin pairs but also their corresponding values for HS-based multiple reversible embedding. Compared with previous approaches, experimental results demonstrate the superiority of the proposed scheme in the terms of embedding capacity and stego-image quality. PMID- 26829813 TI - Superimposed Sparse Parameter Classifiers for Face Recognition. AB - In this paper, a novel classifier, called superimposed sparse parameter (SSP) classifier is proposed for face recognition. SSP is motivated by two phase test sample sparse representation (TPTSSR) and linear regression classification (LRC), which can be treated as the extended of sparse representation classification (SRC). SRC uses all the train samples to produce the sparse representation vector for classification. The LRC, which can be interpreted as L2-norm sparse representation, uses the distances between the test sample and the class subspaces for classification. TPTSSR is also L2-norm sparse representation and uses two phase to compute the distance for classification. Instead of the distances, the SSP classifier employs the SSPs, which can be expressed as the sum of the linear regression parameters of each class in iterations, is used for face classification. Further, the fast SSP (FSSP) classifier is also suggested to reduce the computation cost. A mass of experiments on Georgia Tech face database, ORL face database, CVL face database, AR face database, and CASIA face database are used to evaluate the proposed algorithms. The experimental results demonstrate that the proposed methods achieve better recognition rate than the LRC, SRC, collaborative representation-based classification, regularized robust coding, relaxed collaborative representation, support vector machine, and TPTSSR for face recognition under various conditions. PMID- 26829814 TI - Adaptive Fuzzy Control Design for Stochastic Nonlinear Switched Systems With Arbitrary Switchings and Unmodeled Dynamics. AB - This paper deals with the problem of adaptive fuzzy output feedback control for a class of stochastic nonlinear switched systems. The controlled system in this paper possesses unmeasured states, completely unknown nonlinear system functions, unmodeled dynamics, and arbitrary switchings. A state observer which does not depend on the switching signal is constructed to tackle the unmeasured states. Fuzzy logic systems are employed to identify the completely unknown nonlinear system functions. Based on the common Lyapunov stability theory and stochastic small-gain theorem, a new robust adaptive fuzzy backstepping stabilization control strategy is developed. The stability of the closed-loop system on input state-practically stable in probability is proved. The simulation results are given to verify the efficiency of the proposed fuzzy adaptive control scheme. PMID- 26829815 TI - Erratum: "Ethical Issues in Environmental Health Research Related to Public Health Emergencies: Reflections on the GuLF STUDY". PMID- 26829816 TI - Healthy Ground, Healthy Atmosphere: Recarbonizing the Earth's Soils. PMID- 26829817 TI - Arsenic and Latent Disease Risk: What's the Mechanism of Action? PMID- 26829818 TI - Variable Effectiveness: Assessing Methods to Adjust for Covariates in Biomonitoring. PMID- 26829819 TI - A Clearer Picture of China's Air: Using Satellite Data and Ground Monitoring to Estimate PM2.5 over Time. PMID- 26829820 TI - Arsenic Exposure and the Western Diet: A Recipe for Metabolic Disorders? PMID- 26829821 TI - Evidence-based review and discussion points. PMID- 26829822 TI - Preface. PMID- 26829823 TI - U.S. Dental School Applicants and Enrollees, 2014 Entering Class. AB - This report analyzes data collected annually by the American Dental Education Association (ADEA) on the characteristics of applicants to and first-year enrollees in dental schools. Among the key findings this year are that, since 2010, there has been a gradual decline in the number of individuals taking the Dental Admission Test (DAT), while the number applying to dental schools has remained relatively flat. During the same five-year time period, the number of first-year dental students has continuously increased. The result is an increasing rate of enrollment among applicants. While the overwhelming majority of dental schools utilize some aspect of a holistic admissions process, the DAT scores and grade point averages of applicants and enrollees continue to rise. Unlike a decade ago, women now account for nearly half of all applicants and enrollees. At least part of the gain has come from a decline in the number of men applicants, rather than a change in the enrollment rate. Among underrepresented minorities, there remains a relatively low number of applicants and a lower than average enrollment rate. Overall, by analyzing data about individuals applying to and matriculating in dental schools, this report provides a window into the future dental workforce. PMID- 26829824 TI - The Authors Respond. PMID- 26829825 TI - Global Advisory Committee on Vaccine Safety, 2-3 December 2015. PMID- 26829828 TI - Dr. Fleming Becomes President: Music's Loss Is Medicine's Gain. PMID- 26829827 TI - PECOS Confusion: Who Has to Enroll? Don't Ask. PMID- 26829826 TI - Malaria vaccine: WHO position paper-January 2016. PMID- 26829829 TI - Post-Tsunami Medical Care: Health Problems Encountered in the International Committee of the Red Cross Hospital in Banda Aceh, Indonesia. AB - INTRODUCTION: When the Tsunami struck Asia on 26 December 2004, Aceh, Indonesia suffered more damage than did any other region. After the Tsunami, many humanitarian organizations provided aid in Aceh. For example, the International Committee of the Red Cross (ICRC), along with the Indonesian and Norwegian Red Cross opened a field hospital in Banda Aceh on 16 January 2005. This study describes the illnesses seen in the out-patient department/casualty department (OPD/CD) of the ICRC hospital nine weeks after die Tsunami. It describes the percentage of people seen for problems directly related to the Tsunami, and includes a basic screening for depression and post-traumatic stress disorder (PTSD). METHODS: A prospective, five-day study was performed from 01-05 March 2005. Patients registering in the ICRC field hospital in Banda Aceh were considered for the study. Data collected included: (1) age; (2) gender; (3) diagnosis in the OPD/CD; and (4) whether or not the problem was related directly to the Tsunami. Seven basic questions were asked to screen for depression and PTSD symptoms. RESULTS: Twelve percent of the problems seen in the OPD/CD nine weeks after the Tsunami still were related directly to die Tsunami. Sixty-three percent of patients in the study were male. The medical problems included: (1) urological (19%); (2) digestive (16%); (3) respiratory (12%); and (4) musculoskeletal (12%). Although <2% of patients were diagnosed with a mental health problem, 24% had at least four or more of the seven depression/PTSD symptoms addressed in the study. CONCLUSIONS: Post-earthquake and post-tsunami health problems and medical needs differ from those found in conflict zones. After the Tsunami, both surgical and primary healthcare teams were needed. Many problems were chronic medical problems, which may be indicative of the lack of healthcare infrastructure before the Tsunami. The findings suggest that mental health issues must be taken into consideration for future planning. The ethical issues of performing research in complex emergencies also need further development at the international level. PMID- 26829830 TI - Barriers to Disaster Coordination: Health Sector Coordination in Banda Aceh following the South Asia Tsunami. AB - Ecological disasters impact large populations every year, and hundreds of nongovernmental organizations, thousands of aid workers, and billions of dollars are sent in response. Yet, there have been recurring problems with coordination, leading to wasted efforts and funds. The humanitarian response to the December 2004 Earthquake and Tsunami in Asia was one of the largest ever, and coordination problems were apparent. The coordination processes and attempts at coordination are discussed in this paper. Specific barriers to cooperation are discussed, such as weak leadership, the absence of accountability, the lack of credentialing, the diverse goals of the responding agencies, and the weaknesses in the coordination process itself. PMID- 26829831 TI - Team Echo: Observations and Lessons Learned in the Recovery Phase of the 2004 Asian Tsunami. AB - The 26 December 2004 Tsunami resulted in a death toll of >270,000 persons, making it the most lethal tsunami in recorded history. This article presents performance data observations and the lessons learned by a civilian team dispatched by the Australian government to "provide clinical and surgical functions and to make public health assessments". The team, prepared and equipped for deployment four days after the event, arrived at its destination 13 days after the Tsunami. Aspiration pneumonia, tetanus, and extensive soft tissue wounds of the lower extremities were the prominent injuries encountered. Surgical techniques had to be adapted to work in the austere environment. The lessons learned included: (1) the importance of team member selection; (2) strategies for self-sufficiency; (3) personnel readiness and health considerations; (4) race-to-face handover; (5) coordination and liaison; (6) the characteristics of injuries; (7) the importance of protocols for patient discharge and hospital staffing; and (8) requirements for interpreter services. Whereas disaster medical relief teams will be required in the future, the composition and equipment needs will differ according to the nature of the disaster. National teams should be on standby for international response. PMID- 26829832 TI - Central System of Psychosocial Support to the Czech Victims Affected by the Tsunami in Southeast Asia. AB - The Tsunami disaster affected several countries in Southeast Asia in December 2004 and killed or affected many tourists, most of them from Europe. Eight Czech citizens died, and about 500 Czechs were seriously mentally traumatized. The psychosocial needs of tourists included: (1) protection; (2) treatment; (3) safety; (4) relief; (5) psychological first aid; (6) connecting with family members; (7) transportation home; (8) information about possible mental reactions to trauma; (9) information about the normality of their reaction; (10) procedural and environmental orientation; (11) reinforcement of personal competencies; and (12) psycho-trauma therapy. The Ministry of Foreign Affairs of the Czech Republic was in charge of general emergency management. General coordination of psychosocial support was coordinated under the Ministry of Interior of the Czech Republic, which is connected to the Central Crisis Staff of the Czech Government. The major cooperative partners were: the Ministry of Foreign Affairs, the Ministry of Defence, the Ministry of Health, Czech Airlines, psychosocial intervention teams of the Czech Republic, and the Czech Association of Clinical Psychologists. The main goals of relief workers were: (1) to bring back home the maximum number of Czech citizens; (2) to provide relevant information to the maximum number of affected Czech citizens; (3) to provide relevant information to rescue workers and professionals; and (4) to prepare working psychosocial support regional network. Major activities of the Ministry of Interior (psychology section) included: (1) establishing a psychological helpline; (2) running a team of psychological assistance (assistance in the Czech airports, psychological monitoring of tourists, crisis intervention, psychological first aid, assistance in the collection of DNA material from relatives); (3) drafting and distributing specific information materials (brochures, leaflets, address lists, printed and electronic instructions); (4) communicating via the media and advertising; and (5) providing analysis and research studies. Central coordination of psychosocial support has been found as successful in the first phase after the disaster. The plans must be built for preferable cooperation in the psychosocial field in the Czech Republic. Better collaborates with journalists must exist in order to reduce secondary psycho-trauma. There is a need for intensive international cooperation in the psychosocial field and to build the network at the global level. PMID- 26829833 TI - Response of Thai Hospitals to the Tsunami Disaster. AB - The disaster caused by the Tsunami of 26 December 2004 was one of the worst that medical systems have faced. The aim of this study was to learn about the medical response of the Thai hospitals to this disaster and to establish guidelines that will help hospitals prepare for future disasters. The Israeli Defense Forces (IDF) Home Front Command (HFC) Medical Department sent a research delegation to Thai hospitals to study: (1) pre-event hospital preparedness; (2) patient evacuation and triage; (3) personnel and equipment reinforcement; (4) modes used for alarm and recruitment of hospital personnel; (5) internal reorganization of hospitals; and (6) admission, discharge, and secondary transfer (forward management) of patients. Thai hospitals were prepared for and drilled for a general mass casualty incident (MCI) involving up to 50 casualties. However, a control system to measure the success of these drills was not identified, and Thai hospitals were not prepared to deal with the unique aspects of a tsunami or to receive thousands of victims. Modes of operation differed between provinces. In Phang Nga and Krabi, many patients were treated in the field. In Phuket, most patients were evacuated early to secondary (district) and tertiary (provincial) hospitals. Hospitals recalled staff rapidly and organized the emergency department for patient triage, treatment, and transfer if needed. Although preparedness was deficient, hospital systems performed well. Disaster management should focus on field-based first aid and triage, and rapid evacuation to secondary hospitals. Additionally, disaster management should reinforce and rely on the existing and well-trusted medical system. PMID- 26829834 TI - [ANTIMICROBIAL ACTION OF NOCARDIA VACCINII IMV B-7405 SURFACTANTS]. AB - AIM: To study the effect of Nocardia vaccinii IMV B-7405 surfactants on some bacteria (including pathogens of genera Proteus, Staphylococcus, Enterobacter), yeast of Candida species and fungi (Aspergillus niger R-3, Fusarium culmorum T 7). METHODS: The antimi- crobial properties of surfactant were determined in suspension culture by Koch method and also by index of the minimum inhibitory concentration. Surfactants were extracted from supernatant of cultural liquid by mixture of chloroform and methanol (2:1). RESULTS: It is shown that the antimicrobial properties of N. vaccinii IMV B-7405 surfactant depended on the degree of purification (supernatant, solution of surfactant), concentration and exposure. Survival of Escherichia coli IEM-1 and Bacillus subtilis BT-2 (both vegetative cells and spores) after treatment for 1-2 hours with surfactants solution and the supernatant (the surfactant concentration 21 ug/ml) was 3-28%. Minimum inhibitory concentrations of N. vaccinii IMV B-7405 surfactants on studied bacteria, yeast and micromycetes were 11.5-85.0; 11.5-22.5 and 165.0 325.0 u/ml respectively. CONCLUSIONS: Minimum inhibitory concentrations of N. vaccinii IMV B-7405 surfactants are comparable to those of the known microbial surfactants. The possibility of using the supernatant of culture liquid as an effective antimicrobial agent noticeably simplifies and reduces the cost of the technology of its obtaining. PMID- 26829835 TI - [SEROLOGICAL PROPERTIES AND BIOLOGICAL ACTIVITY OF PANTOEA AGGLOMERANS LIPOPOLYSACCHARIDES]. AB - The serological and phytotoxic properties of lipopolysaccharide (LPS) of plant pathogens--Pantoea agglomerans were studied. It is known that the thin variations in the structure of the O-specific polysaccharides determining serological specificity of gram- negative bacteria and used as a molecular basis of serological classification schemes. For P. agglomerans still does not exist a classification scheme based on serology specificity of their LPS. The results of cross serological tests demonstrate immunochemical heterogeneity of species P agglomerans. Only three strains of the 8488, 8490 and 7969 according to the agglutination of O-antigens and direct hemagglutination and inhibition direct hemagglutination can be attributed to a single serogroup. Other strains--each separate group, although some have a relationship. Compared with control plants under the influence of seed treatment of LPS in plants may be reduced, and in some cases increased root length, height and weight sprout, depending on the strain from which the selected LPS. Dive seedlings of tomatoes in the solutions of the studied preparations FSC caused the loss, and after some time, restore turgor. PMID- 26829836 TI - [SYNTHESIS OF PHYTOHORMONES BY NOCARDIA VACCINII IMV B-7405--PRODUCER OF SURFACTANTS]. AB - AIM: To study the synthesis of phytohormones (auxins, cytokinins, abscisic acid) under cultivation of Nocardia vaccinii IMV B-7405 (surfactants producer) in media containing different carbon sources (glycerol, refined sunflower oil, as well as waste oil after frying potatoes and meat). METHODS: Phytohormones were extracted from supernatants of culture liquid (before or after surfactant separation) by ethylacetate (auxins, abscisic acid) and n-butanol (cytokinins), concentrated and purified by thin-layer chromatography, then quantitative determination was performed using a scanning Sorbfil spectrodensitometer. RESULTS: While growing in medium with refined oil IMV B-7405 strain synthesized 1.8 +/- 0.09 g/l extracellular surfactant, also maximum amount of auxins (245-770 u/l) and cytokinins (134-348 ul). Cultivation of N. vaccini LMV B-7405 on waste oil was accompanied by decreasing amount of phytohormones to 23-84 u/l (auxins) and 16-90 u/l (cytokinins) and increasing surfactant concentration to 2.3-2.6 g/l. The level of abscisic acid synthesis was practically not dependent on the nature of growth substrate, was substantially lower than that of auxins and cytokinins and ranged from 2 to 12 u/l. CONCLUSIONS: Obtained data demonstrate the possibility of using oil-containing industrial waste for the simultaneous synthesis of both surfactants and phytohormones, and indicate the need for studies of the effect of producer cultivation conditions on the biological properties of the target products of microbial synthesis. PMID- 26829837 TI - PHYLOGENETIC ANALYSIS AND AUTECOLOGY OF SPORE-FORMING BACTERIA FROM HYPERSALINE ENVIRONMENTS. AB - Multi-resistant to extreme factors spore-forming bacteria of Bacillus genus are isolated from hypersaline environments of the Crimea (Ukraine) and the Dead Sea (Israel). Phylogenetic analysis showed distinction of dominating extremophilic culturable species in studied regions. In Crimean environments they are B. mojavensis and B. simplex, in the Dead Sea ecosystem--B. subtilis subsp. spizizenii, B. subtilis subsp. subtilis, B. licheniformis and B. simplex. Isolates are simultaneously halotolerant and resistant to UV radiation. Strains isolated from the Dead Sea and the Crimea environments were resistant to UV: LD90 and LD99.99 made 100-170 J/m2 and 750-1500 J/m2 respectively. Spores showed higher UV-resistance (LD99.99-2500 J/m2) than the vegetative cells. However the number of spores made 0.02-0.007% of the whole cell population, and should not significantly affect the UV LD99.99 value. Isolates of both environments were halotolerant in the range of 0.1-10% NaCl and thermotolerant in the range of 20 50 degrees C, and didn't grow at 15 degrees C. Survival strategy of spore forming bacteria from hypersaline environments under high UV radiation level can be performed by spore formation which minimize cell damage as well as efficient DNA-repair systems that remove damages. PMID- 26829838 TI - [SPECIES COMPOSITION OF INFECTIOUS FACTORS THAT CAUSE THE REACTIVE ARTHRITIS DEVELOPMENT AND THEIR EFFECT ON ARGINASE-NO-SYNTHASE REGULATORY SYSTEM OF PERIPHERAL BLOOD LYMPHOCYTES]. AB - The own observations results of urogenital, gastrointestinal and nasopharyngeal infectious factors that cause the development of reactive arthritis (PeA) are being presented. The greatest contribution to the development of this disease make Chlamidia trachomatis (36%), Streptococcus haemolyticus (pyogenes) (19%) and hepatitis viruses B and C (10%). As a result of the research a number of kinetic parameters of arginase and NO-synthase reactions in peripheral blood lymphocytes of patients with reactive arthritis was identified. The authentic increase of arginase activity in 3.3 times and eNO-synthase activity decrease by 1,9 times in peripheral blood lymphocytes of patients with PeA, compared to practically healthy donors were determined. Increased activity of arginase and iNO-synthase of lymphocytes indicates changes in immune cells functional activity, which may be due to impaired metabolic and regulatory processes in these cells caused by a bacterial or viral infection. PMID- 26829839 TI - [BACILLUS STRAINS'S SCREENING--ACTIVE ANTAGONISTS OF BACTERIAL AND FUNGAL PHYTOPATHOGENS]. AB - Antagonistic activity 100 strains of Bacillus bacteria towards to museum and actual strains of phytopathogenic bacteria and fungy was defined. Relation between level of antagonistic activity to phytopathogenic bacteria and genus accessory of the last was shown. The medium level of antagonism to fungal phytopathogens at 30% of the studied strains of Bacillus bacteria was shown. 5 strains of Bacillus sp. with high and medium levels of antagonism to phytopathogens bacterial and fungy nature was selected and considered as perspective for creation of biological preparations for plant protection. PMID- 26829840 TI - [EFFECT OF MYCOPLASMA INFECTION TO FATTY ACID COMPOSITION OF CALLUS CULTURE SUGAR BEET]. AB - It was studied the effect of Acholeplasma laidlawii var. granulum str. 118 to fatty acid composition of sugar beet calluses. It was established that acting of acholeplasma results to changes in the quantitative content of the individual fatty acids and in the qualitative composition of fatty acids in the lipids of calluses. The changing of the fatty acid composition of calluses lipids of sugar beet infected by A. laidlawii vargranulum str. 118 is observed as nonspecific response to biotic stress. PMID- 26829841 TI - [THE SENSITIVITY OF PHYTOPATHOGENIC BACTERIA TO STREPTOMYCIN UNDER THE INFLUENCE OF PESTICIDES]. AB - The results of the streptomycin sensitivity changes of phytopathogenic Pseudomonas syringae and Xanthomonas translucens bacteria under the action of pesticides are pre- sented. It is demonstrated that phytopathogenic strains show greater changes of strepto- mycin sensitivity compared to epiphytic Pantoea agglomerans strain under the pesticides influence. Granstar herbicide, Tviks and Alpha Super insecticides increase the number of streptomycin resistant cells of Xanthomonas translucens 3164, P syringae pv. syringae YKM B-1027 and P syringae pv. atrofaciens YKM B-1011. This fact indicates mutagenic action of these pesticides against researched phytopathogenic bacteria. PMID- 26829842 TI - [MICROBIAL DESTRUCTION MINERAL (OIL) MOTOR OIL]. AB - In a review information is presented about composition of mineral motor oils and their negative impact on the environment and the ability of microorganisms, in particular actinobacteria, to assimilate hydrocarbon oil components. The role of bacteria is described in the process of cleaning up polluted environments motor oils and the prospect of their use in biotechnology, environmental clean-up of these pollutants. PMID- 26829843 TI - Early Detection of Autism (ASD) by a Non-invasive Quick Measurement of Markedly Reduced Acetylcholine & DHEA and Increased beta-Amyloid (1-42), Asbestos (Chrysotile), Titanium Dioxide, Al, Hg & often Coexisting Virus Infections (CMV, HPV 16 and 18), Bacterial Infections etc. in the Brain and Corresponding Safe Individualized Effective Treatment. AB - A brief historical background on Autism & some of the important symptoms associated with Autism are summarized. Using strong Electro Magnetic Field Resonance Phenomenon between 2 identical molecules with identical weight (which received U.S. Patent) non-invasively & rapidly we can detect various molecules including neurotransmitters, bacteria, virus, fungus, metals & abnormal molecules. Simple non- invasive measurement of various molecules through pupils & head of diagnosed or suspected Autism patients indicated that in Autism patients following changes were often found: 1) Acetylcholine is markedly reduced; 2) Alzheimer's disease markers (i.e. beta-Amyloid (1-42), Tau Protein, Apolipoprotein (Apo E4)) are markedly increased; 3) Chrysotile Asbestos is increased; 4) Titanium Dioxide (TiO2) is moderately increased; 5) Al is moderately increased; 6) Hg is moderately increased; 7) Dopamine, Serotonin & GABA are significantly reduced (up to about 1/10 of normal); 8) Often viral infections (such as CMV, HHV-6, HPV-16, HPV-18, etc.), and Bacterial infections (such as Chlamydia trachomatis, Mycobacterium TB, Borrelia Burgdorferi, etc.) coexist. Research by others on Autism spectrum disorder (ASD) shows that it is a group of complex neurodevelopmental disorders, with about 70% of ASD patients also suffering from gastro-intestinal problems. While Alzheimer disease (AD) is characterized by formation of 1) Amyloid plaques, 2) Neurofibrillary tangles inside of neurons, and 3) Loss of connections between neurons. More than 90% of AD develops in people over the age of 65. These 3 characteristics often progressively worsen over time. Although Autism Spectrum Disorder and Alzheimer's disease are completely different diseases they have some similar biochemical changes. Eight examples of such measurement & analysis are shown for comparison. Most of Autism patients improved significantly by removing the source or preventing intake of Asbestos, TiO2, Al & Hg or enhancing urinary output of above abnormal substances & coexisting infections, if treatment is given early. When HPV-16 & HPV-18 coexist, at triangular central area of the top of head, in addition to inability to talk, severe neuromuscular problems of lower extremity were found to also exist. However, if treatment is given 3-4 years after onset of Autism symptoms, even when successful biochemical reduction of above abnormal substances occurs, clinical improvement is less significant, since permanent damage in brain tissue seems to already exist. Therefore, early diagnosis & early treatment is very important for both Autism & Alzheimer's disease. In addition the optimal doses of Vitamin D3 and Taurine may play an important role in the future treatment of Autism, Alzheimer's Disease and memory disturbances by significantly increasing Acetylcholine and DHEA levels, enhancing the excretion of toxic substances in the urine, as well as having an anticancer effect. PMID- 26829844 TI - A New Theory on the Evaluation of Traditional Chinese Acupuncture Mechanisms from the Latest Medical Scientific Point of View. AB - Acupuncture is a key component of traditional Chinese medicine involving the insertion of needles through the skin at specific points on the body to achieve therapeutic effects and is an ancient Chinese art of healing. Using ancient scientific principles, acupuncture treats illnesses by bringing a person's body into harmony and regulating the balance of Yin and Yang. Balancing Yin and Yang is one basic principle of Chinese medicine, and balancing methods for combination of meridians and acupoints have been described throughout the history of Chinese medicine. Clinical observations and principal research on acupuncture focus on the adjustment of the Zang-Fu organ and have shown that the adjustment by acupuncture relied largely on the effective components in different organs. What does this effectiveness mean? In fact, is acupuncture a treatment that shows its effects with signals to the autocrine, paracrine and endocrine pathways? What role does embryology play in this area? Furthermore, molecular biology has opened avenues to newer methods for the study of embryology and to enhance our understanding of growth and development. Can evaluation of acupuncture with these branches of science be more scientific? We discuss this interesting topic in this original article. After all this time, it is reasonable that different therapeutic techniques and approaches are developed for acupuncture. PMID- 26829845 TI - Beneficial Acupuncture Treatment For Systemic Sclerosis which was Non-Responsive To Medications. AB - Although various drugs have been used in the treatment of systemic sclerosis, a disease-modifying drug that can be a gold standard is yet to be defined. The effects of acupuncture treatment used in inflammatory diseases on systemic sclerosis patients are not clearly known. This report presents the successful outcome of acupuncture treatment applied to two female systemic sclerosis patients who had suffered from the disease for seven years (aged 54 years) and 30 years (aged 65 years), despite the use of various drugs. PMID- 26829846 TI - [MORPHO-FUNCTIONAL CHARACTERISTIC OF ENTEROBACTERIA ADHESIVE ACTIVITY]. AB - AIM: Study adhesive activity of enterobacteria in the model of hemagglutination reaction with animal and avian erythrocytes and clarify structures responsible for adhesion in enterobacteria. MATERIALS AND METHODS: 58 cultures of enterobacteria were used, of which: 21 Escherichia coli strains, 13 Citrobacter spp., 11 Morganella morganii, 9 Proteus spp., 4 Hafnia alvei. Erythrocytes of various animals and birds were used in hemagglutination reaction. Electron microscopical studies were carried out in JEM-100B (Japan) electron microscope. RESULTS: Use of avian erythrocytes as a target of adhesion determination, compared with animal erythrocytes, has shown that bacteria can cause D-mannose sensitive hemagglutination reaction, linked with the presence of 110 - 420 nm long and 5.0 - 5.4 nm wide cilia in the microorganisms. CONCLUSION: Adhesion of enterobacteria was shown to be a complex process, depending on the presence of certain fimbrial structures, use of those results in specific interaction of the microbe with certain host cell receptors. Avian erythrocytes are a model target cells. PMID- 26829847 TI - [EFFECT OF TEMPERATURE ON THE VIABILITY OF PLANKTON CELLS AND MODEL LEGIONELLA PNEUMOPHILA BIOFILMS IN WATER]. AB - AIM: Study the effect of water temperature from 40 to 70 degrees C on viability of plankton forms and model Legionella pneumophila under experimental conditions. MATERIALS AND METHODS: Monospecies legionella biofilms, obtained in plates for enzyme immunoassay during 96 hours at 28 degrees C, and water suspension of BCYE agar cultivated cells of L. pneumophila at a concentration of 10(3) - 10(5) CFU per liter were used in the study for evaluation of bactericidal effect of temperature on various legionella forms. RESULTS: Analysis of effects of various temperature regimens on plankton forms and model legionella biofilms has shown that at a temperature range from 50 to 60 degrees C a significant reduction of quantity of viable legionella cells occurs. Model legionella biofilms have partially conserved viability at a temperature of 60 degrees C and only exposition to a temperature of 70 degrees C resulted in death of legionella biofilms and plankton forms of bacteria. A dependence of viability conservation of legionella from the initial concentration of the causative agent in water and duration of exposition at varying temperature was shown. CONCLUSION: Short-term heating at a temperature of at least 70 degrees C has the most pronounced bactericidal effect on plankton forms and model L. pneumophila biofilms under experimental conditions. Such temperature regimen could be used as one of the prophylaxis approaches during maintenance of especially dangerous water system and, fist of all, systems of hot water supply. PMID- 26829848 TI - [UNIVERSALITY OF CHANGES IN EPIDEMIC PROCESS MANIFESTATIONS OF ANTHROPONOSIS INFECTIONS IN RECENT DECADES]. AB - AIM: Detection of main regularities of anthroponosis infections with various degrees of manageability and factors that determine them in contemporary social demographic conditions. MATERIALS AND METHODS: A comparative retrospective epidemiologic analysis of morbidity of the population with viral hepatitis A, Sonnei and Flexneri shigellae, rotavirus infection, pertussis, diphtheria, varicella, rubella, pneumococcal infection and possible risk factors by 47 European countries and territories of Russian Federation was carried out, the maximum depth of search was 89 years. RESULTS: Common epidemiologic regularities were shown to be characteristic for anthroponosis infection regardless of the degree of their manageability, that are manifested by the presence of large and small cycles in the multi-year dynamics of morbidity changes of age-related morbidity structure and its pronounced territorial non-uniformity. Intensity of epidemic process of anthroponosis infections and features of its manifestation were established to be determined largely by demographic conditions, size of the child population, including those attending child preschool establishments, number of child preschool establishments and the degree of their admission. A decrease of morbidity with many child infections took place against the background of reduction of the child population in the age structure. CONCLUSION: Universality of changes in the manifestations of epidemiologic process of anthroponosis infections is largely determined by features of the demographic situation. PMID- 26829849 TI - [SPECIFIC IMMUNE RESPONSE TO CERTAIN CAPSULE POLYSACCHARIDES OF STREPTOCOCCUS PNEUMONIAE IN HEALTHY BLOOD DONORS AND INDIVIDUALS IMMUNIZED WITH PNEUMOCOCCAL VACCINES]. AB - AIM: Evaluate humoral immune IgG response to 13 specific capsule polysaccharides in healthy blood donors and individuals immunized with pneumococcal vaccines. MATERIALS AND METHODS: A solid-phase EIA method was used with sorption on polystyrol of pneumococcal CPS isolated by us (1, 3, 4, 6A, 6B, 7F, 9N, 9V, 14, 18C, 19A, 19F, 23F). Blood sera of 140 healthy donors, 42 conscripts (young males) vaccinated with Pneumo-23 and 5 adults that are frequently ill with various bronchial-lung diseases for a long time and vaccinated with Prevenar-13 preparation were analyzed. IgG level was expressed in conventional units. RESULTS: The mean level of antibodies against pneumococcal CPS in donors was at the level of 70. c.u.; in conscripts during the prevaccination period--50 c.u.; in frequently ill for a long time--90 c.u. In 14 of 140 donors increased antibody levels against one or several CPS simultanously were observed. During post vaccinal period in vaccinated with Pneumo-23 an increase of antibody levels against 12 - 13 CPS varying by specificity was observed only in 9 of 42 individuals; 1 individual did no have an increase of antibody levels against any of the 13 CPS; in 32 of 42--the antibody levels against 1 or several CPS did not increase. In 5 individuals vaccinated with Prevenar-13 a rise of antibody levels against 1 - 9 CPS, that are included in the vaccine, was not detected. CONCLUSION: Thus, clinical trials during registration of newly developed vaccines should, in our opinion, include evaluation of the initial levels of specific antibodies against each polysaccharide component of the vaccine in blood sera of all groups of volunteers. This would allow to evaluate the effectiveness of the vaccination. PMID- 26829850 TI - [COLD-ADAPTED A/KRASNODAR/101/35/59 (H2N2) STRAIN--A PROMISING STRAIN-DONOR OF ATTENUATION FOR PROCURATION OF LIVE INFLUENZA VACCINES]. AB - AIM: Study of ts, ca, att phenotype, immunogenicity and protective effectiveness of reassortants obtained by a way of recombination of a new influenza cold adapted (ca) strain donor of attenuation A/Krasnodar/101/35/59 (H2N2) and virulent strain of influenza virus. MATERIALS AND METHODS: Viruses were used: ca strain A/Krasnodar/101/35.59 (H2N2), virulent strains: A/Kumamoto/102/02 (H3N2) and A/Bern/07/95. For determination of ts and ca phenotype, titration of viruses in chicken embryos was carried out simultaneously at optimal, decreased and increased temperature. Protective effect of immunization was evaluated during intranasal infection of mice with a virulent strain of influenza virus. RESULTS: All the obtained reassortants possessed 6 internal genes from strain-donor of attenuation and 2 genes, coding HA and NA-proteins from virulent strains. Ca reassortants were characterized by ts and ca phenotype, had antigenic specificity and good immunogenicity, had high protective effectiveness. CONCLUSION: The data obtained indicate on the perspectiveness of ca strain A/Krasnodar/101/35/59 (H2N2)as a donor of attenuation for live influenza vaccines. PMID- 26829851 TI - [EFFECTIVENESS OF FULLERENE-(TRIS-AMINOCAPRONIC ACID) HYDRATE IN THE MODEL OF EXPERIMENTAL VIRAL-BACTERIAL PNEUMONIA OF MICE]. AB - AIM: Study the effectiveness of the substance and various drug formulations of fullerene-(tris-aminocapronic acid) hydrate (FTAAH onwards) in the model of experimental viral-bacterial pneumonia of mice. MATERIALS AND METHODS: BALB/c mice were infected with influenza virus A/California/04/2009 and subsequently infected with Staphylococcus aureus. The animals were treated after viral infection with the substance and various drug forms of FTAAH, as well as comparative preparations--oseltamivir and arbidol. Therapy effectiveness was evaluated by clinical indicators (survival, lifespan, animal mass decrease reduction), virological (virus titer), microbiological (density of bacteria in lungs) parameters, confirmed by pathomorphological characteristics of lungs. RESULTS: FTAAH therapy in injectable form was effective in the model of a combined viral-bacterial pneumonia of mice by all the studied criteria: treatment increased mice survival, reduced the decrease of their body weight, resulted in a reduction of virus titers and density of bacteria in lungs, that correlated with the data from morphological study and signs of bronchopneumonia resolution in mice. FTAAH therapy in rectal form depended on animal infection schemes, as well as preparation dose, increasing with its increase. CONCLUSION: FTAAH substance is effective in the model of experimental viral-bacterial pneumonia of mice. PMID- 26829852 TI - [A PERSPECTIVE CULTURAL MODEL FOR CONTROL OF BIOLOGICAL ACTIVITY OF HUMAN INTERFERONS]. AB - AIM: Study species specificity of human lymphocyte interferon alpha in vitro in cell cultures of swine origin for expansion of cell line spectrum for interferon titration and control of newly created interferons and interferon-like preparations in vivo in mini-pig model. MATERIALS AND METHODS: Cell cultures of various species origin were used: Vero (monkey kidney), MDBK (bull kidney), HEK 293T (human embryo kidney), PK-15 (swine kidney), SPEV(swine embryo kidney), PTP (swine testicles), MDCK (canine kidney), RK-13 (rabbit kidney). Human lymphocyte interferon alpha (hINF-alpha) from Biomed company (1000 IU/ml), established in MDBK cells, was tested. Vesicular stomatitis virus (Indiana strain) was used. Human plasma was obtained from heparin-treated venous blood in the process of human peripheral blood lymphocyte isolation in medium for lymphocyte separation (Ficoll with a density of 1.077 g/cm3). RESULTS: Vesicular stomatitis virus, adapted to Vero cells, was established to have the least active reproduction in Vero and MDBK and reproduces more actively in cell of swine origin by 0.25 - 0.75 lg TCD50. At the same time, virus, adapted to cells of swine origin, reproduces more actively by 2 - 3 lg TCD50 in both cells of swine origin and Vero and MDBK. CONCLUSION: A possibility of titration of hINF-alpha in cells of swine origin was shown for both 100 doses of the indicator virus and low virus doses (5 and 10). This allows to determine low titers of hINF-alpha in blood plasma as one of the important indicators of interferon status--sera hINF-alpha. PMID- 26829853 TI - [EFFECT OF LACTOBACILLI EXOPOLYSACCHARIDES ON PHAGOCYTE AND CYTOKINE ACTIVITY IN VITRO AND IN ANIMAL ORGANISM DURING INFECTIOUS PROCESS MODELING]. AB - AIM: Study the effect of lactobacilli exopolysaccharides (EPS)on cytokine and phagocyte activity in vitro and in mice organism during modelling of an infectious process. MATERIALS AND METHODS: Lactobacillus delbrueckii subsp. delbrueckii B-1596 (laksaran 1596), L. delbrueckii B-1936 (laksaran 1936) and L. delbrueckii ssp. bulgaricus (laksaran Z) were used in the study. EPS were administered into white mice 1 hour after the Staphylococcus aureus 209-P infection. Index of phagocyte completion and index of killing activation (IKA) were calculated during phagocyte activity study. IL-1alpha, TNF-alpha, IFN-gamma and IL-4 cytokine content was determined in blood sera and macrophage supernatants. RESULTS: Laksaran 1596, 1936 and Z had ambiguous effect on cytokine production. Laksaran: Z and 1936, 6 hours after mice infection increased IL-1 content in blood sera. Laksaran Z had the most pronounced effect on macrophages, resulting in an increase of active macrophages, facilitating increased digestion of S. aureus 209-P and IKA increase, stimulated cytokine production. CONCLUSION: The results obtained allow to speak about a possibility of using laksaran Z as a prophylaxis immune modulating preparation for correction of animal cytokine status. PMID- 26829854 TI - [ADENOVIRUSES IN THE ETIOLOGICAL STRUCTURE OF ACUTE RESPIRATORY VIRAL INFECTION IN MOSCOW IN 2004 - 2014]. AB - AIM: Study prevalence of adenovirus species and serotypes that had caused acute respiratory viral infection (ARVI) in Moscow in 2004 - 2014. MATERIALS AND METHODS: Material from respiratory tract of 4731 patients with ARVI and 663 conditionally healthy children and adults was used. ARVI causative agents were detected by PCR with real-time detection using AmpliSens reagent kits (CRIE, Moscow). Membership of adenoviruses to a certain serotype was determined by sequencing of hexon gene segment. Adenoviruses that had caused ARD in servicemen in 2010 - 2014 were also studied. RESULTS: ARVI causative agents were detected in 64.6% ill children and 58% of adults. Respiratory-syncytial and rhinoviruses prevailed in children, influenza A virus--in adults. Adenoviruses were detected in 6.9% of ill children and 2.9% of adults during the whole year, with a rise in October-December. B and C species occurred at an equal frequency, E species was found less often. Serotypes 3 and 2 prevailed in 34% and 21% of cases of adenovirus mono-infection, respectively, serotypes 7, 6 and 4 occurred less often. 4 out of 5 outbreaks of adenovirus infection in servicemen were caused by serotype 7. Adenoviruses were absent in the group of healthy adults, in conditionally healthy children were detected in 0.4% of cases and were attributed to serotypes 1 and 2. CONCLUSION: Etiological structure of ARVI was studied for the last decade. Adenovirus infection ranked 5th in children and 7th in adults. 9 serotypes of 3 species of respiratory adenoviruses were identified. Varying prevalence of species and serotypes depending in season, clinical diagnosis and patient age was demonstrated. PMID- 26829855 TI - [STUDY OF HUMORAL IMMUNE RESPONSE FEATURES BASED ON MODELLING OF ANTIGEN DETERMINANTS OF HEPATITIS C VIRUS BY SYNTHETIC PEPTIDES AND GENETICALLY ENGINEERED POLYPEPTIDES]. AB - AIM: Study of humoral immune response features in patients with acute hepatitis C (AHC) with various disease outcomes based on modelling of antigen determinants of hepatitis C virus (HCV) by synthetic peptides and genetically engineered polypeptides. MATERIALS AND METHODS: 20 patients with icteric form of AHC based on clinical-biochemical presentation and HCV RNA detection by PCR in blood sera during 12 months from the disease onset were included into the study. Antibody seroconversion study was carried out by EIA. Genetically engineered proteins and synthetic peptides were used as antigens. RESULTS: Similarity and differences of humoral immune response against the HCV antigens used in this study depending on the disease outcome (convalescence or chronicity) were shown. Significant difference of the humoral immune response to both HCV core protein and various fragments of the immune dominant region of this protein were detected, that indicates on a link of these features of immune response with perspectives of a more or less favorable disease development. CONCLUSION: The regularities of seroconversion detected allow to consider anti-NS5 IgG as a prognostic marker of the disease chronicity. Such marker, as anti-NS3 IgG, is important for diagnostics, but not for disease outcome prognosis. PMID- 26829856 TI - [STUDY OF COLONIZATION PROCESSES AND PERSISTENCE OF MICROORGANISMS IN ARTIFICIAL MATERIALS FOR MEDICAL USE]. AB - AIM: Study processes of microbial colonization and persistence of microorganisms in polymer materials for medical use. MATERIALS AND METHODS: Samples (1 x 1 cm plates) of polymer plastics for production of removable dental prosthesis based on polyurethane and acryl were used, that were incubated with clinical isolates of Pseudomonas aeuruginosa, Staphylococcus aureus in Luria-Bertani broth nutrient media for 24, 48 hours and 7, 14 days and for 1, 5 and 3 months at a temperature of 37 degrees C. Dynamics of interaction process of microorganisms with polymer materials were studied using scanning electron microscope Quanta 200 3D (FEI Company, USA). The samples were fixated after incubation with 10% of neutral formaldehyde, dehydration with alcohols or acetone, typical for SEM, was not carried out, that allowed to conserve the native structure of the samples, including exo-cell matrix of biofilms. RESULTS: Electron-microscopical data on stages of interaction of bacteria with the surface of medical plastics were obtained. Biofilms were shown to be formed on abiotic surfaces and biodestructive changes of plastics appeared. A question on the possibility of prolonged persistence of pathogenic for human microorganisms in artificial prosthesis is discussed. CONCLUSION: The developed experimental model of formation of biofilm on abiotic surfaces could be the basis for carrying out studies directed on the fight with biofilms, by using SEM. PMID- 26829857 TI - [USE OF LASER RAMAN-LUMINESCENT TECHNOLOGIES FOR EVALUATION OF QUALITY OF MEAT PRODUCTS AND DETERMINATION OF THE DEGREE OF THEIR BACTERIAL CONTAMINATION]. AB - AIM: Determination of the effect of microorganisms on spoilage of meat products during various temperature regimes of storage by integral indexes of luminescent lines in their spectra and development of an algorithm of microorganism indication by an express method using laser Raman-luminescent spectroscopy. MATERIALS AND METHODS: Minced meat from beef and pork was used. Determination of quantity of mesophilic aerobic and opportunistic-anaerobic microorganisms was carried out by serial 10-fold dilutions with subsequent parallel seeding into Rida count total 24 plates and Petri dishes with 5% blood agar. Sample study was carried out in luminescent software-hardware complex Enspectr L405 (a variant of Enspectr M software-hardware complexes). RESULTS: Meat spoilage was established to be caused to a large degree by Pseudomonas genus (P. fluorescens, P. putida, P. fragi et al.) bacterial growth. Raman-luminescent spectra of bacteria that compose microflora, characterizing and accompanying beef and pork spoilage, were measured and recorded into a database. CONCLUSION: The results obtained will allow to use this technique in the future for both express-indication and differentiation of microorganisms and express-evaluation of quality of meat products at all stages of their manufacturing, storage, transport and realization. PMID- 26829858 TI - [RATIONAL ASPECTS OF BACTERIOPHAGES USE]. AB - AIM: Analysis of existing aspects of bacteriophage use and study features of their lytic activity by using various techniques. MATERIALS AND METHODS: Effect of monophages and associated bacteriophages (staphylococci, piopolyvalent and piocombined, intestiphage, pneumonia klebsiella and polyvalent klebsiella produced by "Microgen") was studied with 380 strains of Staphylococcus aureus and 279 cultures of Klebsiella pneumoniae in liquid and solid nutrient media. From patients with intestinal disorder, sensitivity was analyzed to 184 strains of Salmonella genus bacteria 18 serological variants to salmonella bacteriophages, 137 strains of Escherichia coli (lactose-negative, hemolytic), as well as some members of OKA groups (21 serovars) to coli-proteic and piopolyvalent bacteriophages. Lytic ability of the piobacteriophage against Klebsiella and Proteus genus bacteria was determined. RESULTS: Staphylococcus aureus was sensitive to staphylococcus bacteriophage in 71.6% of cases and to piobacteriophage--in 86.15% of cases. A 100% lytic ability of salmonella bacteriophage against Salmonella spp. was established. Sensitivity of E. coli of various serogroups to coli-proteic and piobacteriophage was 66 - 100%. Klebsiella, Proteus genus bacteria were sensitive to piobacteriophage in only 35% and 43.15% of cases, respectively. CONCLUSION: A more rational use of bacteriophages is necessary: development of a technique, evaluation of sensitivity of bacteria to bacteriophage, introduction of corrections into their production (expansion of bacteriophage spectra, determination and indication of their concentration in accompanying documents). PMID- 26829859 TI - [EFFECT OF INTACT BIONANOSTRUCTURES--LIPOSOMES ON BIOCHEMICAL AND IMMUNOLOGICAL STATUS OF THE ORGANISM]. AB - Due to features of its structure and biological properties, liposomes became not only a useful model for study of cell membranes of various organs and tissues, but also unique transporters of drugs and vaccines in the organism. At the same time, biological effect on humans and animals of the preparations included into them significantly increases. An increasingly wider use of liposomes in medicine, biology and certain adjacent specialties necessitates further studies of their effect on macroorganism, generalization, systematization and analysis of already available data. Questions of effect of intact and "empty" liposomes on biochemical and immunological parameters of the organism are examined in the review. Analysis of the ability of liposomes to render biological effect depending on their composition, preparation method and administration route is carried out. These data should be taken into consideration during creation of liposome drugs and vaccines. PMID- 26829860 TI - [ADJUVANTED INFLUENZA VACCINES: DATA FROM DIRECT COMPARATIVE STUDIES]. AB - Vaccines are the cornerstone of influenza control, however available vaccines are subject to certain limitations. Adjuvanted vaccines are a promising approach, however available adjuvants have a suboptimal effectiveness and safety profile. Data from direct comparative trials are necessary for selection of optimal adjuvants among currently available and search for novel safe and effective adjuvants for next generation influenza vaccines. Data from published direct comparative studies of adjuvants for influenza vaccines are summarized, a lack of such studies is noted, especially those using adequate methods and designs and comparing adjuvants of major groups (nature/source and mechanism of action). Several promising approaches of adjuvant research and development could be identified: chitosan-based adjuvants, oil-in-water emulsions and multi-component formulations (depot + immune modulating components). PMID- 26829861 TI - [EPIDEMIOLOGIC ANALYSIS OF OUTBREAKS OF DISEASES CAUSED BY AMERICAN EQUINE ENCEPHALITIS CAUSATIVE AGENTS IN ENDEMIC REGIONS]. AB - Epidemiologic analysis of epidemic outbreaks caused by American equine encephalitis causative agents is carried out in the review. Eastern equine encephalomyelitis (EEE), Western equine encephalomyelitis (WEE) and Venezuela equine encephalomyelitis (VEE) viruses are etiologic agents of dangerous transmissive diseases that are usually accompanied by fever and neurologic symptoms. Among the New World alphaviruses, VEE virus has the most potential danger for humans and domestic animals. Currently, enzootic strains of VEE play an increasing role as etiologic agents of human diseases. Most of the VEE cases in humans in endemic regions during inter-epidemic period are caused by infection with VEE subtype ID virus. A possibility of emergence of novel epidemic outbreaks of VEE is determined by mutations of ID subtype strains into IC subtype, and those currently pose a potential threat as an etiologic agent of the disease. Despite low morbidity, EEE and WEE are a problem for healthcare due to a relatively high frequency of lethal outcomes of the disease. PMID- 26829862 TI - [SOME ASPECTS OF NON-SPECIFIC PROPHYLAXIS AND THERAPY OF ESPECIALLY DANGEROUS INFECTIONS]. AB - Recently, due to spread of dangerous and especially dangerous infections much attention is given to development of complex approaches to their prophylaxis and therapy. Data on use of immune modulators, cytokines, probiotics, preparations of plant origin for non-specific prophylaxis of especially dangerous infections are analyzed in the review, and expediency of their combined use with specific and emergency prophlaxis of these diseases is evaluated. PMID- 26829863 TI - [USING MODERN INFORMATION TECHNOLOGY IN THE PRACTICE OF THE SANITARY EPIDEMIOLOGICAL SURVEILLANCE DURING THE XXVII WORDWIDE YEARS UNIVERSITY GAME OF 2013 IN KAZAN]. PMID- 26829864 TI - [Personal e-cards for military personnel and military-medical information system]. AB - The article presents main directions of activities of the medical service, dealing with implementation of personal electronic cards for military personnel, organizing the process of automation of medical service management, military and medical organizations and health care departments. The given article, reveals the on-going activity, concerning creation of the military-medical information system, which will unite all medical units, organizations, and governments into one information space. PMID- 26829865 TI - [Consequences learned from the use of chemical weapons during the First World War for the modern military medicine]. AB - The article describes the way medical service dealed with problems resulted from the use of chemical weapons during the First World War (1914-1918). It was revealed that many of the abovementioned problems remain unsolved up to the present moment. It is stated the existence of the threat of use of chemical weapons in modem military conflicts, which expands the area of responsibility for medical chemical protection. The authors proved necessity and algorithm of the training system, considered as a part of medical protection in case of adverse factors of chemical nature. PMID- 26829866 TI - [Plastic reconstruction of soft tissue defects of extremities resulted from gunshot with the help of triangular flap]. AB - Plastic reconstruction of soft tissue defects of extremities' resulted from gunshot with the help of triangular flap. The authors suggested an original technique of plastic surgery of round and oval-shaped gunshot wounds of soft tissues with the use. of triangular flap. The core of technique is to move triangular skin flap in the form of the letter <> and <>. By moving this flap, as well as stretching and displacement of surrounding tissue. It is possible to close the occured defect. The authors describe 32 surgical interventions on the upper and lower limbs in 21 wounded, defect size ranged from 2x2 cm to 12x18 cm. Closure of defects was performed during the period from 5 to 22 days after injury. As a result of the treatment the primary wound healing was observed in 87,5% of cases. In 12,5% of the wounded was observed marginal necrosis that healed after the second intervention. and didn't require repeated plastic reconstruction. Patients didn't get rough tightening scars affecting joint movement after the .plastic reconstruction. All patients achieved good cosmetic and functional results. The proposed method-has several advantages over dermatomal plastic reconstruction, and before transplanting islet skin-facial flap in free and non-free versions. It is technically easier and does not require special software and tools. PMID- 26829867 TI - [New approaches to the diagnosis, treatment and rehabilitation of military personnel, military pensioners and their family members with arterial hypertension]. AB - The article considers new approaches to diagnosis, treatment and rehabilitation of patients with arterial hypertension (AH) applied to the Ministry of Defence contingent. For the medical service of the Armed Forces the problem is relevant because of the significant labor losses, high level of dismission, morbidity and mortality of this disease. In the assessment of the patients limitation of life should be considered a variant AH, the stage, availability and seventy of the organ damage, severity and reversibility of complications, the incidence and severity of hypertensive crises, the effectiveness of treatment, comorbidity, education, occupation, the presence of contra-types and conditions of military service or labor. Military medical expertise of soldiers with AH uses the classification of degrees of arterial hypertension of 2010 and a three-stage classification hypertonic disease created by the World Health Organization, 1996. PMID- 26829868 TI - [The complex of neurological symptoms of substance abuse]. AB - Standard neurological examination was performed in 85 patients of military service age (the average age was 32,6+/-5,3 years - from 19 to 44 years) with a confirmed diagnosis of substance abuse, caused by the use of narcotic drugs and psychotropic substances: cocaine and amphetamine in 12 patients, opioids - in 73 patienls. Some symptoms of nervous system damage had statistically characteristic peculiarities for different forms of substance abuse. Mydriasis, signs a bilateral pyramidal insufficiency, hyperkinetic disorder are often characteristic for cocaine and amphetamine abuse. Opioid abuse is characterised by more severe symptoms of nervous system damage, disseminated neurologic symptomatic and polyneurotic disorders. Symptoms of neurasthenia and vegetative-vascular dystonia, which are usually accompanied by the; symptoms of organic lesions of the central and peripheral nervous system, were observed in all patients with substance abuse. In order to detect the symptoms of nervous system damage in patients, which are supposed to be conscribe, it is necessary to take medical history. PMID- 26829869 TI - [New technologies in diagnostics and health-resort treatment of movement disorder in children with cerebral palsy]. AB - The study analyses results of treatment of 196 patients, with cerebral palsy, which underwent a course of health-resort treatment is performed. Past medical history of patients for the last 10 years was also analysed. It was found that the use of botulin toxin <> (BT-A) <> as a part of complex rehabilitation of the patients significantly improved the effectiveness of the treatment. It was determined that the reasons of the lack of spasticity reduce are caused by degeneration of the muscles. The developed technique of ultrasound exam muscles allowed objectively evaluates the degree of muscle degeneration. PMID- 26829870 TI - [Prospects of computer-assisted assessment of functional health status of military personnel]. AB - The article is devoted to the development of:an integrated system for remote assessment of the functional state of the military serivcemen. A review of domestic and foreign literature concerning this problem is presented and proposed a new look and approach to monitoring the combat capability of the military servicemen. The authors carried out analysis of the possibility of using accumulated experience and the use of high-tech means to solve an assigned task at the level <> and gave a concrete way to solve this task at the current stage to improve the quality of health care and the efficiency of professional activity of servicemen. PMID- 26829871 TI - [International legal aspects of responsibility of states and international organizations for the spread of epidemics, pandemics and mass disease]. AB - The present article deals with international legal issues that arise in case when various mass diseases go beyond any national jurisdiction. The emphasis is made on the problem of international responsibility, which different actors have to bear in such cases. The authors also examine the implementation of responsibility mechanism, including the indentication of the relevant international court, authorized to establish such liability and identify the specific forms of its realization. PMID- 26829872 TI - [Medical Service of the Latvian National Armed Forces]. AB - The article is a brief description of the current state of the Latvian National Armed Forces medical service and is based on the study of the open access foreign sources. At the beginning, the general information about Latvia, its Armed Forces, and their medical service is presented. Then the medical service particular features are described with more detail, namely, the organization of inpatient and outpatient treatment, medical supply, scientific research, combat medicine, medical staff education and training, medical service personnel income. PMID- 26829873 TI - [Who was the head of the General Military Medical Department in 1917-1918]. AB - The article describes the history of the central governing body of the Russian military medicine - the General Military Medical-Department (GMMD) - during the most difficult period of its history - 1917-1918. There is still no clear evidence about the head of GMMD of those times in historical literature. The authors tried to reconstruct the history of GMMD during the revolution, gave the list of chiefs in chronological order on the basis of primary documents of the central military archives. The authors provide some biographical information about professors V.A. Yurevich and N.N. Burdenko, and also about A. Ya.Evdokimov, A.A. Tsvetaev and others, who headed GMMD, etc. for the first time. PMID- 26829874 TI - [The General Military Medical Department during the Great Patriotic War]. AB - The article is devoted to the contribution of the General Military Medical Department of the Red Army (GMMD) to organisation of health care support during the Great Patriotic War of 1941-1945. In the summary you may follow the main ways of activity of the central governing body of medical (health) services of the Red. Army. The main focus of the article is made on conditions under which GMMD had to organize medical support of the Red. Army at the beginning of the war, the most difficult period of the Great Patriotic War. The authors payed attention to the forms and methods of the work of the head of GMMD and its subordinate departments under the conditions of rapidly changing environment of combat and rear situation, as well as interaction with GMMD People Commissariat of Health. The authors tried to highlight not well known but not less important moments in the activities of the Red Army GMMD. PMID- 26829875 TI - [Legal regulation of the personnel issues of military medicine during the reign of Paul I]. AB - The article describes laws and regulations concerning the Russian army and navy, and accordingly its medical services accepted during the reign of Paul I. During this period different decrees aimed to improve medical personnel training in order to admit students to medical and surgical schools, reorganization of educational medical institutions, improving of professional skills of medical workers. Other decrees, aimed to improvement of recruitment of medical personnel of troops: the best students of <> had to be sent to troops instead physician assistant, medical staff increase and additional funding, countering the reduce of physicians' social welfare due to the inhumane attitude of the authorities, to regulate of the military medical service rotation order as well as assessment of their professional, moral, and psychological qualities. PMID- 26829876 TI - Modular Total Syntheses of the Alkaloids Discoipyrroles A and B, Potent Inhibitors of the DDR2 Signaling Pathway. AB - The title natural product 1 has been synthesized by treating the 1,2,3,5 tetrasubstituted pyrrole 23 with oxoperoxymolybdenum(pyridine) (hexamethylphosphoric triamide) (MoOPH). Compound 23 was itself prepared in seven steps from parent pyrrole using Ullmann-Goldberg and Suzuki-Miyaura cross coupling, Vilsmeier-Haack formylation, electrophilic bromination, and Wittig olefination reactions as key steps. Related chemistry has been used to prepare discoipyrrole B (2). PMID- 26829877 TI - Persistence of the immune response after MenACWY-CRM vaccination and response to a booster dose, in adolescents, children and infants. AB - Persistence of bactericidal antibodies following vaccination is extremely important for protection against invasive meningococcal disease, given the epidemiology and rapid progression of meningococcal infection. We present an analysis of antibody persistence and booster response to MenACWY-CRM, in adolescents, children and infants, from 7 clinical studies. Immunogenicity was assessed using the serum bactericidal assay with both human and rabbit complement. Post-vaccination hSBA titers were high, with an age- and serogroup specific decline in titers up to 1 y and stable levels up to 5 y The waning of hSBA titers over time was more pronounced among infants and toddlers and the greatest for serogroup A. However, rSBA titers against serogroup A were consistently higher and showed little decline over time, suggesting that protection against this serogroup may be sustained. A single booster dose of MenACWY-CRM administered at 3 to 5 y induced a robust immune response in all age groups. PMID- 26829878 TI - Neurologic findings caused by ossification of ligamentum flavum at the thoracolumbar junction. AB - OBJECTIVE: To evaluate neurologic findings caused by a single ossification of ligamentum fravum (OLF) and identify the level of the lumbar segment of spinal cord. DESIGN: Retrospective study. METHODS: Subjects were 28 patients with a single OLF at T10-11 level (15 patients), T11-12 (11), and T12-L1 (2). The tip of the conus medullaris was assessed using computed tomographic myelography or magnetic resonance imaging. Neurologic evaluations were performed for patellar tendon reflex (PTR), sensory disturbance, and motor weakness. RESULTS: The tip of the conus medullaris was located at the L1 vertebral body level. At the T10-11 level, all patients showed hyperreflexia of PTR. Sensory disturbance was observed for L1 dermatome and weakness of the iliopsoas was noted. At the T11-12 level, 8 of 11 patients didn't show hyperreflexia of PTR. Sensory disturbance was observed for L5 dermatome and weakness of the tibialis anterior was noted. At the T12-L1 level, all patients showed normal reflex of PTR, sensory disturbance of L5 dermatome, and weakness of the tibialis anterior. CONCLUSION: With regard to the relationship between PTR and OLF level, all patients at the T10-11 level showed involvement of the L3 segment of spinal cord proximally. On the other hand, most patients at the T11-12 level showed involvement of the L4 segment of spinal cord distally. From all neurologic findings, we confirmed the presence of the L4 segment of spinal cord from the lower third of T11 vertebral body to the T11-12 intervertebral disc level. PMID- 26829879 TI - Toward a Boron-Doped Ultrananocrystalline Diamond Electrode-Based Dielectrophoretic Preconcentrator. AB - This paper presents results on immunobeads-based isolation of rare bacteria and their capture at a boron-doped ultrananocrystalline diamond (BD-UNCD) electrode in a microfluidic dielectrophoretic preconcentrator. We systematically vary the bead surface chemistry and the BD-UNCD surface chemistry and apply dielectrophoresis to improve the specific and the nonspecific capture of bacteria or beads. Immunobeads were synthesized by conjugating antibodies to epoxy /sulfate, aldehyde-/sulfate, or carboxylate-modified beads with or without poly(ethylene glycol) (PEG) coimmobilization. The carboxylate-modified beads with PEG provided the highest capture efficiency (~65%) and selectivity (~95%) in isolating live Escherichia coli O157:H7 from cultures containing 1000 E. coli O157:H7 colony-forming units (cfu)/mL, or ~500 E. coli O157:H7 and ~500 E. coli K12 cfu/mL. Higher specificity was achieved with the addition of PEG to the antibody-functionalized bead surface, highest with epoxy-/sulfate beads (85-86%), followed by carboxylate-modified beads (76-78%) and aldehyde-/sulfate beads (74 76%). The bare BD-UNCD electrodes of the preconcentrator successfully withstood 240 kV/m for 100 min that was required for the microfluidic dielectrophoresis of 1 mL of sample. As expected, the application of dielectrophoresis increased the specific and the nonspecific capture of immunobeads at the BD-UNCD electrodes; however, the capture specificity remained unaltered. The addition of PEG to the antibody-functionalized BD-UNCD surface had little effect on the specificity in immunobeads capture. These results warrant the fabrication of electrical biosensors with BD-UNCD so that dielectrophoretic preconcentration can be performed directly at the biosensing electrodes. PMID- 26829880 TI - Does the type of parenteral lipids matter? A clinical hint in critical illness. AB - BACKGROUND & AIMS: An altered lipid profile is common among intensive care unit (ICU) patients, but evidence regarding the impact of different fatty acid (FA) emulsions administered to patients requiring parenteral nutrition (PN) is scarce. This study aimed to compare the plasma triglycerides (TG) response to two types of commercial lipid emulsions: a structured mixture of long- and medium-chain triglycerides (LCT/MCT) or LCTs with n-9 FA (LCT+) in ICU patients. METHODS: In this retrospective observational study conducted in a multidisciplinary ICU: two groups were defined by the type of emulsion used. Inclusion criteria were: consecutive patients on PN staying >=4 days with one TG determination before commencing PN and at least one during PN. Recorded variables included energy intake, amount and type of nutritional lipids, propofol dose, glucose and protein intake, laboratory parameters, and all drugs received. Hypertriglyceridemia (hyperTG) was defined as TG >2 mmol/L. RESULTS: The dynamic impact of the emulsion was analyzed in 187/757 patients completing the inclusion criteria (112 LCT/MCT and 75 LCT+). The demographic variables, severity indices, diagnostic categories, and outcomes did not differ between the two groups. Seventy-seven patients (41%) presented hyperTG. Both groups received similar daily energy (1604 versus 1511 kcal/day), lipids (60 versus 61 g/day), and glucose intake (233 versus 197 g/day). There was no increase of TG concentration in those receiving the LCT/MCT emulsion compared to those receiving the LCT+ emulsion (0 and 0.2 mmol/L, respectively, p < 0.05). CONCLUSION: LCT/MCT emulsions are associated with a less pronounced increase of plasma TG levels than LCT+ emulsions. PMID- 26829881 TI - [One-staged surgical technique for scrotal calcinosis]. AB - INTRODUCTION: Idiopathic calcinosis cutis is a rare condition involving the development of scrotal nodules in the skin and subcutaneous tissue. Although it is a benign disease, patient's quality of life can be importantly impaired. OBJECTIVE: We report herein our experience and surgical management of diffuse scrotal calcinosis. MATERIAL AND METHODS: From 2012 and 2015, 7 patients who suffered of diffuse scrotal calcinosis cutis were included in this study. We performed a one-staged resection of the lesions by an elliptic resection centered on the scrotal median raphe as a scrotal lift shape. Outcomes including sexual quality of life and patient's satisfaction were assessed with a questionnaire. RESULTS: No postoperative complication occurred. Aesthetic result was high and sexual quality of life was importantly improved. No recurrence was observed in a 2-year follow-up. DISCUSSION: This disease is a pathological condition of unknown origin and hence is idiopathic. Multi-staged resection of the nodules are often performed despite being a time-consuming and expensive approach. Our one-staged treatment increased the patient's quality of life and self-esteem. CONCLUSION: We present a one-staged treatment of scrotal calcinosis cutis that is simple and effective. Aesthetic and functional results were achieved. LEVEL OF EVIDENCE: 5. PMID- 26829882 TI - The activation of the NF-kappaB-JNK pathway is independent of the PI3K-Rac1-JNK pathway involved in the bFGF-regulated human fibroblast cell migration. AB - BACKGROUND: Skin wound healing is a complex process that repairs multiple organ tissues. Fibroblasts are key players of skin cells, whose migration is important during wound healing process. bFGF has shown a great efficacy to promote cell migration, but the precise mechanism by which bFGF regulates cell migration remains elusive. OBJECTIVE: The aim of this study was to find bFGF-regulated gene pools and further identify target molecules that participated in human fibroblast cell migration. METHODS: Skin primary fibroblasts and rat skin wound model were used to demonstrate the novel mechanism of bFGF regulating cell migration to accelerate wound healing. Cell migration was determined using the wound healing scratch assay. The differentially expressed genes and numerous biochemical pathways after bFGF treatment were identified by RNA-Seq analysis, and differentially expressed genes were further verified by qRT-PCR. siRNA duplex target to interfering the expression of PI3-kinase (p110alpha) was transformed into NIH/3T3 cells. Western blotting analysis was used to determine marker protein expressions. The invasive activity of fibroblasts was measured using 3D spheroid cell invasion assay. RESULTS: RNA-Seq analysis identified numerous biochemical pathways including the NF-kappaB pathway under the control of FGF signaling. bFGF negatively regulates the phosphorylation of IkappaB-alpha, the most well studied NF-kappaB signaling regulator while bFGF induces JNK phosphorylation. Application of Bay11-7082, a representative NF-kappaB inhibitor promoted cell migration, invasion and enhanced the JNKs phosphorylation. However, inhibition of JNKs blocked cell migration when NF-kappaB is inhibited. Moreover, application of the PI3K inhibitor LY294002 together with Bay11-7082 maintained normal cell migration and knocking-down PI3K (p110alpha) by a specific siRNA inhibited JNKs phosphorylation while maintaining normal IkappaBalpha phosphorylation, indicating that PI3K and NF-kappaB signaling independently regulate JNKs activation. In addition, administration of bFGF or Bay11-7082 promoted rat skin wound repair and accelerated the invasion of fibroblasts. CONCLUSION: This study sheds light on the mode of action of bFGF and identifies that the NF-kappaB-JNKs pathway is independent of the PI3K-JNKs pathway to accelerate fibroblast migration. In addition, bFGF and the relief of inflammation could be a favorable therapeutic approach for skin wound healing. PMID- 26829884 TI - Maternal high-fat feeding in pregnancy programs atherosclerotic lesion size in the ApoE*3 Leiden mouse. AB - Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high-fat diet in utero, programed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28 days postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (P<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol; however, transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared with wild-type controls (P=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R 2=0.563, P<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol two-fold higher than in chow-fed mothers, P=0.011). The data strongly suggest that maternal hypercholesterolemia programs later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models. PMID- 26829883 TI - Exposure to viral and bacterial pathogens among Soay sheep (Ovis aries) of the St Kilda archipelago. AB - We assessed evidence of exposure to viruses and bacteria in an unmanaged and long isolated population of Soay sheep (Ovis aries) inhabiting Hirta, in the St Kilda archipelago, 65 km west of Benbecula in the Outer Hebrides of Scotland. The sheep harbour many metazoan and protozoan parasites but their exposure to viral and bacterial pathogens is unknown. We tested for herpes viral DNA in leucocytes and found that 21 of 42 tested sheep were infected with ovine herpesvirus 2 (OHV-2). We also tested 750 plasma samples collected between 1997 and 2010 for evidence of exposure to seven other viral and bacterial agents common in domestic Scottish sheep. We found evidence of exposure to Leptospira spp., with overall seroprevalence of 6.5%. However, serological evidence indicated that the population had not been exposed to border disease, parainfluenza, maedi-visna, or orf viruses, nor to Chlamydia abortus. Some sheep tested positive for antibodies against Mycobacterium avium subsp. paratuberculosis (MAP) but, in the absence of retrospective faecal samples, the presence of this infection could not be confirmed. The roles of importation, the pathogen-host interaction, nematode co infection and local transmission warrant future investigation, to elucidate the transmission ecology and fitness effects of the few viral and bacterial pathogens on Hirta. PMID- 26829885 TI - Discriminating Multiple Emotional States from EEG Using a Data-Adaptive, Multiscale Information-Theoretic Approach. AB - A multivariate sample entropy metric of signal complexity is applied to EEG data recorded when subjects were viewing four prior-labeled emotion-inducing video clips from a publically available, validated database. Besides emotion category labels, the video clips also came with arousal scores. Our subjects were also asked to provide their own emotion labels. In total 30 subjects with age range 19 70 years participated in our study. Rather than relying on predefined frequency bands, we estimate multivariate sample entropy over multiple data-driven scales using the multivariate empirical mode decomposition (MEMD) technique and show that in this way we can discriminate between five self-reported emotions (p < 0.05). These results could not be obtained by analyzing the relation between arousal scores and video clips, signal complexity and arousal scores, and self reported emotions and traditional power spectral densities and their hemispheric asymmetries in the theta, alpha, beta, and gamma frequency bands. This shows that multivariate, multiscale sample entropy is a promising technique to discriminate multiple emotional states from EEG recordings. PMID- 26829886 TI - D-Allose Inhibits Cancer Cell Growth by Reducing GLUT1 Expression. AB - Glucose is a major energy source for mammalian cells and is transported into cells via cell-specific expression of various glucose transporters (GLUTs). Especially, cancer cells require massive amounts of glucose as an energy source for their dysregulated growth and thus over-express GLUTs. d-allose, a C-3 epimer of d-glucose, is one of rare sugars that exist in small quantities in nature. We have shown that d-allose induces the tumor suppressor gene coding for thioredoxin interacting protein (TXNIP) and inhibits cancer cell growth by G1 cell cycle arrest. It has also been reported that GLUTs including GLUT1 are over-expressed in many cancer cell lines, which may contribute to larger glucose utilization. Since d-allose suppresses the growth of cancer cells through the upregulation of TXNIP expression, our present study focused on whether d-allose down-regulates GLUT1 expression via TXNIP expression and thus suppresses cancer cell growth. Western blot and real-time PCR analyses revealed that d-allose significantly induced TXNIP expression and inhibited GLUT1 expression in a dose-dependent manner in three human cancer cell lines: hepatocellular carcinoma (HuH-7), Caucasian breast adenocarcinoma (MDA-MB-231), and neuroblastoma (SH-SY5Y). In these cell lines, d-allose treatment inhibited cell growth. Importantly, d-allose treatment decreased glucose uptake, as measured by the uptake of 2-deoxy d glucose. Moreover, the reporter assays showed that d-allose decreased the expression of luciferase through the hypoxia response element present in the tested promoter region. These results suggest that d-allose may cause the inhibition of cancer growth by reducing both GLUT1 expression and glucose uptake. PMID- 26829888 TI - Observing mesoscale eddy effects on mode-water subduction and transport in the North Pacific. AB - While modelling studies suggest that mesoscale eddies strengthen the subduction of mode waters, this eddy effect has never been observed in the field. Here we report results from a field campaign from March 2014 that captured the eddy effects on mode-water subduction south of the Kuroshio Extension east of Japan. The experiment deployed 17 Argo floats in an anticyclonic eddy (AC) with enhanced daily sampling. Analysis of over 3,000 hydrographic profiles following the AC reveals that potential vorticity and apparent oxygen utilization distributions are asymmetric outside the AC core, with enhanced subduction near the southeastern rim of the AC. There, the southward eddy flow advects newly ventilated mode water from the north into the main thermocline. Our results show that subduction by eddy lateral advection is comparable in magnitude to that by the mean flow--an effect that needs to be better represented in climate models. PMID- 26829887 TI - Digital detection of endonuclease mediated gene disruption in the HIV provirus. AB - Genome editing by designer nucleases is a rapidly evolving technology utilized in a highly diverse set of research fields. Among all fields, the T7 endonuclease mismatch cleavage assay, or Surveyor assay, is the most commonly used tool to assess genomic editing by designer nucleases. This assay, while relatively easy to perform, provides only a semi-quantitative measure of mutation efficiency that lacks sensitivity and accuracy. We demonstrate a simple droplet digital PCR assay that quickly quantitates a range of indel mutations with detection as low as 0.02% mutant in a wild type background and precision (<=6%CV) and accuracy superior to either mismatch cleavage assay or clonal sequencing when compared to next-generation sequencing. The precision and simplicity of this assay will facilitate comparison of gene editing approaches and their optimization, accelerating progress in this rapidly-moving field. PMID- 26829889 TI - Topological nodal-line fermions in spin-orbit metal PbTaSe2. AB - Topological semimetals can support one-dimensional Fermi lines or zero dimensional Weyl points in momentum space, where the valence and conduction bands touch. While the degeneracy points in Weyl semimetals are robust against any perturbation that preserves translational symmetry, nodal lines require protection by additional crystalline symmetries such as mirror reflection. Here we report, based on a systematic theoretical study and a detailed experimental characterization, the existence of topological nodal-line states in the non centrosymmetric compound PbTaSe2 with strong spin-orbit coupling. Remarkably, the spin-orbit nodal lines in PbTaSe2 are not only protected by the reflection symmetry but also characterized by an integer topological invariant. Our detailed angle-resolved photoemission measurements, first-principles simulations and theoretical topological analysis illustrate the physical mechanism underlying the formation of the topological nodal-line states and associated surface states for the first time, thus paving the way towards exploring the exotic properties of the topological nodal-line fermions in condensed matter systems. PMID- 26829890 TI - Precursor and mature NGF live tracking: one versus many at a time in the axons. AB - The classical view of nerve growth factor (NGF) action in the nervous system is linked to its retrograde axonal transport. However, almost nothing is known on the trafficking properties of its unprocessed precursor proNGF, characterized by different and generally opposite biological functions with respect to its mature counterpart. Here we developed a strategy to fluorolabel both purified precursor and mature neurotrophins (NTs) with a controlled stoichiometry and insertion site. Using a single particle tracking approach, we characterized the axonal transport of proNGF versus mature NGF in living dorsal root ganglion neurons grown in compartmentalized microfluidic devices. We demonstrate that proNGF is retrogradely transported as NGF, but with a lower flux and a different distribution of numbers of neurotrophins per vesicle. Moreover, exploiting a dual color labelling technique, we analysed the transport of both NT forms when simultaneously administered to the axon tips. PMID- 26829891 TI - Integration or separation in the processing of facial properties--a computational view. AB - A face recognition system ought to read out information about the identity, facial expression and invariant properties of faces, such as sex and race. A current debate is whether separate neural units in the brain deal with these face properties individually or whether a single neural unit processes in parallel all aspects of faces. While the focus of studies has been directed toward the processing of identity and facial expression, little research exists on the processing of invariant aspects of faces. In a theoretical framework we tested whether a system can deal with identity in combination with sex, race or facial expression using the same underlying mechanism. We used dimension reduction to describe how the representational face space organizes face properties when trained on different aspects of faces. When trained to learn identities, the system not only successfully recognized identities, but also was immediately able to classify sex and race, suggesting that no additional system for the processing of invariant properties is needed. However, training on identity was insufficient for the recognition of facial expressions and vice versa. We provide a theoretical approach on the interconnection of invariant facial properties and the separation of variant and invariant facial properties. PMID- 26829893 TI - A comprehensive review of the diagnosis and management of prosthetic joint infections in the absence of positive cultures. AB - The diagnosis and management of prosthetic joint infections (PJI) with negative cultures remains an enigma without clear definitions and guidelines for its management. In contrast, the literature offers guidelines to the diagnosis and management of culture positive prosthetic joint infections as noted in both the infectious disease literature and the orthopedic literature. This paper outlines the current state of knowledge of PJI with negative cultures and summarizes the recommendations for the work up and management of this condition. In addition, we propose a simple algorithm that clinicians may find useful for the management of PJI with negative cultures. This algorithm has not been validated with data at this point, but can be applied to practice to help direct the management and diagnosis of prosthetic joint infections in the absence of positive cultures. PMID- 26829892 TI - Urinary tract infection in children after cardiac surgery: Incidence, causes, risk factors and outcomes in a single-center study. AB - Nosocomial urinary tract infection (UTI) increases hospitalization, cost and morbidity. In this cohort study, we aimed to determine the incidence, risk factors, etiology and outcomes of UTIs in post-operative cardiac children. To this end, we studied all post-operative patients admitted to the Pediatric Cardiac Intensive Care Unit (PCICU) in 2012, and we divided the patients into two groups: the UTI (UTI group) and the non-UTI (control group). We compared both groups for multiple peri-operative risk factors. We included 413 children in this study. Of these, 29 (7%) had UTIs after cardiac surgery (UTI group), and 384 (93%) were free from UTIs (control group). All UTI cases were catheter-associated UTIs (CAUTIs). A total of 1578 urinary catheter days were assessed in this study, with a CAUTI density rate of 18 per 1000 catheter days. Multivariate logistic regression analysis demonstrated the following risk factors for CAUTI development: duration of urinary catheter placement (p<0.001), presence of congenital abnormalities of kidney and urinary tract (CAKUT) (p<0.0041) and the presence of certain syndromes (Down, William, and Noonan) (p<0.02). Gram-negative bacteria accounted for 63% of the CAUTI. The main causes of CAUTI were Klebsiella (27%), Candida (24%) and Escherichia coli (21%). Resistant organisms caused 34% of CAUTI. Two patients (7%) died in the UTI group compared with the one patient (0.3%) who died in the control group (p<0.05). Based on these findings, we concluded that an increased duration of the urinary catheter, the presence of CAKUT, and the presence of syndromes comprised the main risk factors for CAUTI. Gram-negative organisms were the main causes for CAUTI, and one-third of them found to be resistant in this single-center study. PMID- 26829894 TI - Incidence and economic burden of prosthetic joint infections in a university hospital: A report from a middle-income country. AB - In this study, we aimed to evaluate the incidence and economic burden of prosthetic joint infections (PJIs) in a university hospital in a middle-income country. Surveillance data between April 2011 and April 2013 in the Orthopedic Surgery Department was evaluated. Patients (>16 years old) who had primary arthroplasty in Erciyes University were included in the study, and patients with preoperative infection were excluded. Patients were followed up during their stay in the hospital and during readmission to the hospital for PJI by a trained Infection Control Nurse. During the study period, 670 patients were followed up. There were 420 patients (62.7%) with total hip arthroplasty (THA), 241 (36.0%) with total knee arthroplasty (TKA) and 9 (1.3%) with shoulder arthroplasty (SA). The median age was 64, and 70.6% were female. The incidence of PJI was 1.2% (5/420) in THA, 4.6% (11/241) in TKA and 0% (0/9) in SA. PJI was significantly more prevalent in TKA (p=0.029). All of the PJIs showed early infection, and the median time for the development of PJI was 23.5 days (range 7-120 days). The median total length of the hospital stay was seven times higher in PJI patients than patients without PJI (49 vs. 7 days, p=0.001, retrospectively). All hospital costs were 2- to 24-fold higher in patients with PJI than in those without PJI (p=0.001). In conclusion, the incidence and economic burden of PJI was high. Implementing a national surveillance system and infection control protocols in hospitals is essential for the prevention of PJI and a cost-effective solution for the healthcare system in low-middle-income countries. PMID- 26829895 TI - Role of radiation therapy in melanomas: Systematic review and best practice in 2016. AB - Radiotherapy has been used for skin cancers since early after the discovery of X rays. The introduction of sophisticated surgery techniques and information of the general population on potential late radiation-induced toxicity and carcinogenesis have led to limiting indications in the dermatologist community. However, radiotherapy (RT) has undergone considerable developments, essentially including technological advances, to sculpt radiation delivery, with demonstration of the benefit either alone or after adding concomitant cytotoxic agents or targeted therapies. Although side effects due to high doses and/or the use of old RT techniques have been significantly decreased, the risk of atrophic scars, ulcerations or secondary cancers persist. In this systematic review, we aim to discuss indications for RT in melanomas with focus on new advances that may lead to rehabilitating this treatment option according to the tumor radiosensitivity and clinical benefit/risk ratio. Melanomas have been considered as radioresistant tumors for many years. PMID- 26829897 TI - Pentamethylcyclopentadienyl-rhodium and iridium complexes containing (N^N and N^O) bound chloroquine analogue ligands: synthesis, characterization and antimalarial properties. AB - The synthesis and characterization of twenty new pentamethylcyclopentadienyl rhodium and iridium complexes containing N^N and N^O-chelating chloroquine analogue ligands are described. The in vitro antimalarial activity of the new ligands as well as the complexes was evaluated against the chloroquine sensitive (CQS) NF54 and the chloroquine resistant (CQR) Dd2 strains of Plasmodium falciparum. The antimalarial activity was found to be good to moderate; although all complexes are less active than artesunate, some of the ligands and complexes showed better activity than chloroquine (CQ). In particular, rhodium complexes were found to be considerably more active than iridium complexes against the CQS NF54 strain. Salicylaldimine Schiff base ligands having electron-withdrawing groups (F, Cl, Br, I and NO2) in para position of the salicyl moiety and their rhodium complexes showed good antiplasmodial activity against both the CQS-NF54 and the CQR-Dd2 strains. The crystal structures of (eta(5) pentamethylcyclopentadienyl){N(1)-(7-chloroquinolin-4-yl)-N(2)-(pyridin-2 ylmethyl)ethane-1,2-diamine)} chlororhodium(III) chloride and (eta(5) pentamethylcyclopentadienyl){(4-chloro-2-(((2-((7-chloroquinolin-4 yl)amino)ethyl)imino)methyl)phenolate)}chlororhodium(III) chloride are reported. The crystallization of the amino-pyridyl complex (eta(5) pentamethylcyclopentadienyl){(N(1)-(7-chloroquinolin-4-yl)-N(2)-(pyridin-2 ylmethyl)ethane-1,2-diamine)}chloroiridium(III) chloride in acetone resulted in the formation of the imino-pyridyl derivative (eta(5) pentamethylcyclopentadienyl){(N1-(7-chloroquinolin-4-yl)-N2-(pyridin-2 ylmethylene)ethane-1,2-diamine)}chloroiridium(III) chloride, the crystal structure of which is also reported. PMID- 26829896 TI - Improving nucleoside analogs via lipid conjugation: Is fatter any better? AB - In the past few decades, nucleoside analog drugs have been used to treat a large variety of cancers. These anti-metabolite drugs mimic nucleosides and interfere with chain lengthening upon incorporation into the DNA or RNA of actively replicating cells. However, efficient delivery of these drugs is limited due to their pharmacokinetic properties, and tumors often develop drug resistance. In addition, nucleoside analogs are generally hydrophilic, resulting in poor bioavailability and impaired blood-brain barrier penetration. Conjugating these drugs to lipids modifies their pharmacokinetic properties and may improve in vivo efficacy. This review will cover recent advances in the field of conjugation of phospholipids to nucleoside analogs. This includes conjugation of myristic acid, 12-thioethyldodecanoic acid, 5-elaidic acid esters, phosphoramidate, and self emulsifying formulations. Relevant in vitro and in vivo data will be discussed for each drug, as well as any available data from clinical trials. PMID- 26829898 TI - Monocular perceptual learning of contrast detection facilitates binocular combination in adults with anisometropic amblyopia. AB - Perceptual learning in contrast detection improves monocular visual function in adults with anisometropic amblyopia; however, its effect on binocular combination remains unknown. Given that the amblyopic visual system suffers from pronounced binocular functional loss, it is important to address how the amblyopic visual system responds to such training strategies under binocular viewing conditions. Anisometropic amblyopes (n = 13) were asked to complete two psychophysical supra threshold binocular summation tasks: (1) binocular phase combination and (2) dichoptic global motion coherence before and after monocular training to investigate this question. We showed that these participants benefited from monocular training in terms of binocular combination. More importantly, the improvements observed with the area under log CSF (AULCSF) were found to be correlated with the improvements in binocular phase combination. PMID- 26829899 TI - Continuous Magnetoelectric Control in Multiferroic DyMnO3 Films with Twin-like Domains. AB - The magnetic control of ferroelectric polarization is currently a central topic in the multiferroic researches, owing to the related gigantic magnetoelectric coupling and fascinating physics. Although a bunch of novel magnetoelectric effect have been discovered in multiferroics of magnetic origin, the manipulation of polarization was found to be fundamentally determined by the microscopic origin in a certain multiferroic phase, hindering the development of unusual magnetoelectric control. Here, we report emergent magnetoelectric control in DyMnO3/Nb:SrTiO3 (001) films showing twin-like domain structure. Our results demonstrate interesting magnetically induced partial switch of polarization due to the coexistence of polarizations along both the a-axis and c-axis enabled by the twin-like domain structure in DyMnO3 films, despite the polarization-switch was conventionally believed to be a one-step event in the bulk counterpart. Moreover, a continuous and periodic control of macroscopic polarization by an in plane rotating magnetic field is evidenced in the thin films. This distinctive magnetic manipulation of polarization is the consequence of the cooperative action of the twin-like domains and the dual magnetic origin of polarization, which promises additional applications using the magnetic control of ferroelectricity. PMID- 26829901 TI - The carbonic anhydrase domain of plant mitochondrial complex I. AB - The mitochondrial NADH dehydrogenase complex (complex I) consists of several functional domains which independently arose during evolution. In higher plants, it contains an additional domain which includes proteins resembling gamma-type carbonic anhydrases. The Arabidopsis genome codes for five complex I-integrated gamma-type carbonic anhydrases (gammaCA1, gammaCA2, gammaCA3, gammaCAL1, gammaCAL2), but only three copies of this group of proteins form an individual extra domain. Biochemical analyses revealed that the domain is composed of one copy of either gammaCAL1 or gammaCAL2 plus two copies of the gammaCA1/gammaCA2 proteins. Thus, the carbonic anhydrase domain can have six distinct subunit configurations. Single and double mutants with respect to the gammaCA/gammaCAL proteins were employed to genetically dissect the function of the domain. New insights into complex I biology in plants will be reviewed and discussed. PMID- 26829900 TI - ALDH18A1-related cutis laxa syndrome with cyclic vomiting. AB - Cutis laxa (CL) syndromes are connective tissue disorders characterized by redundant, sagging, inelastic and wrinkled skin, with organ involvement. Here, we describe a patient with ALDH18A1-related CL who developed cyclic vomiting. The patient was a 12-year-old boy who presented with poor postnatal growth, hypotonia, short stature, joint hyperlaxity, microcephaly, strabismus, bilateral cataracts, facial dysmorphism and severe mental retardation. Bone radiographs showed osteopenia and osteoporosis, and magnetic resonance angiography showed marked kinking and tortuosity of the brain vessels. These findings were clinically compatible with ALDH18A1-related CL. Molecular analysis revealed a de novo heterozygous mutation (p.R138Q) in ALDH18A1. No mutations were found in PYCR1 gene. The patient developed cyclic vomiting with decreased blood levels of ornithine, citrulline, arginine and proline without hyperammonemia and other hypoaminoacidemias were also found. ALDH18A1 encodes Delta(1)-pyrroline-5 carboxylate synthase, which is related to the biosynthesis of ornithine, citrulline, arginine, and proline. Cyclic vomiting has never been reported in other ALDH18A1-related CL patients. This is the first case report of ALDH18A1 related CL with cyclic vomiting associated with amino acid abnormalities. PMID- 26829902 TI - Uncertainty principle for experimental measurements: Fast versus slow probes. AB - The result of a physical measurement depends on the time scale of the experimental probe. In solid-state systems, this simple quantum mechanical principle has far-reaching consequences: the interplay of several degrees of freedom close to charge, spin or orbital instabilities combined with the disparity of the time scales associated to their fluctuations can lead to seemingly contradictory experimental findings. A particularly striking example is provided by systems of adatoms adsorbed on semiconductor surfaces where different experiments--angle-resolved photoemission, scanning tunneling microscopy and core level spectroscopy--suggest different ordering phenomena. Using most recent first principles many-body techniques, we resolve this puzzle by invoking the time scales of fluctuations when approaching the different instabilities. These findings suggest a re-interpretation of ordering phenomena and their fluctuations in a wide class of solid-state systems ranging from organic materials to high temperature superconducting cuprates. PMID- 26829903 TI - Enhanced recovery protocols for major upper gastrointestinal, liver and pancreatic surgery. AB - BACKGROUND: 'Fast-track surgery' or 'enhanced recovery protocol' or 'fast-track rehabilitation', incorporating one or more elements of preoperative education, pain relief, early mobilisation, enteral nutrition and growth factors, may improve health-related quality of life and reduce length of hospital stay and costs. The role of enhanced recovery protocols in major upper gastrointestinal, liver and pancreatic surgery is unclear. OBJECTIVES: To assess the benefits and harms of enhanced recovery protocols compared with standard care (or usual practice) in major upper gastrointestinal, liver and pancreatic surgery. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane Library; 2015, Issue 3), MEDLINE, EMBASE and Science Citation Index Expanded until March 2015 to identify randomised trials. We also searched the references of included trials to identify further trials. SELECTION CRITERIA: We considered only randomised controlled trials (RCTs) performed in people undergoing major upper gastrointestinal, liver and pancreatic surgery, irrespective of language, blinding or publication status for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials and independently extracted data. We calculated the risk ratio (RR), mean difference (MD), or standardised mean difference (SMD) with 95% confidence intervals (CIs) using both fixed-effect and random-effects models using Review Manager 5, based on available case analysis. MAIN RESULTS: Ten studies met the inclusion criteria for the review, and nine studies provided information on one or more outcomes for the review. A total of 1014 participants were randomly assigned to the enhanced recovery protocol (499 participants) or standard care (515 participants) in the nine RCTs. Most of the trials included low anaesthetic risk participants with high performance status undergoing different upper gastrointestinal, liver and pancreatic surgeries. Eight trials incorporated more than one element of the enhanced recovery protocol. All of the trials were at high risk of bias. The overall quality of evidence was low or very low.None of the trials reported long-term mortality, medium-term health-related quality of life(three months to one year), time to return to normal activity, or time to return to work. The difference between the enhanced recovery protocol and standard care were imprecise for short-term mortality (enhanced recovery protocol: 4/425 (adjusted proportion = 0.6%); standard care: 1/443 (0.2%); seven trials; 868 participants; RR 2.79; 95% CI 0.44 to 17.73; very low quality evidence), proportion of people with serious adverse events (enhanced recovery protocol: 4/157 (adjusted proportion = 0.6%); standard care: 0/184 (0.0%); two trials; 341 participants; RR 5.57; 95% CI 0.68 to 45.89; very low quality evidence), number of serious adverse events (enhanced recovery protocol: 34/421 (8 per 100 participants); standard care: 46/438 (11 per 100 participants); seven trials; 859 participants; rate ratio 0.72; 95% CI 0.45 to 1.13; very low quality evidence), health-related quality of life (four trials; 373 participants; SMD 0.29; 95% CI -0.04 to 0.62; very low quality evidence) and hospital readmissions (enhanced recovery protocol: 14/355 (adjusted proportion = 3.3%); standard care: 9/378 (2.4%); seven trials; 733 participants; RR 1.4; 95% CI 0.69 to 2.87; very low quality evidence). The enhanced recovery protocol group had a lower proportion of people with mild adverse events (enhanced recovery protocol: 31/254 (adjusted proportion = 10.9%); standard care: 51/271 (18.8%); four trials; 525 participants; RR 0.58; 95% CI 0.39 to 0.85; low quality evidence), fewer number of mild adverse events (enhanced recovery protocol: 69/499 (13 per 100 participants); standard care: 128/515 (25 per 100 participants); nine trials; 1014 participants; rate ratio 0.52; 95% CI 0.39 to 0.70; low quality evidence), shorter length of hospital stay (nine trials; 1014 participants; MD -2.19 days; 95% CI -2.53 to -1.85; low quality evidence) and lower costs (four trials; 282 participants; MD USD -6300; 95% CI -8400 to -4200; low quality evidence) than standard care group. AUTHORS' CONCLUSIONS: Based on low quality evidence, enhanced recovery protocols may reduce length of hospital stay and costs (primarily because of reduction in hospital stay) in people undergoing major upper gastrointestinal, liver and pancreatic surgeries. However, the validity of the results is uncertain because of the risk of bias in the trials and the way the outcomes were measured. Future RCTs should be conducted with low risk of bias, and measure clinically important outcomes for including the three months to one year period. PMID- 26829905 TI - Seroprevalence of Ehrlichia ruminantium antibodies and its associated risk factors in indigenous goats of South Africa. AB - The present study investigated the seroprevalence of antibodies to Ehrlichia ruminantium and the associated risk factors in goats from five different farming provinces of South Africa. Sera collected from 686 goats of the commercial meat type (n=179), mohair type (n=9), non-descript indigenous goats from Eastern Cape (n=56), KwaZulu-Natal (n=209), Limpopo (n=111), North West (n=61) and Northern Cape (n=11) provinces and a feral Tankwa goat (n=50) were tested for the presence of immunoglobulin G (IgG) antibodies to antigens of E. ruminantium using the indirect fluorescent-antibody test (IFAT). Fifty two percent of these goats had ticks. The overall seroprevalence of antibodies to E. ruminantium was 64.87% (445/686) with the highest seroprevalence reported for Limpopo (95.50%) and lowest for Northern Cape (20.29%). Highest seroprevalence for antibodies to E. ruminantium was observed in goats from endemic regions (76.09%), and from smallholder production systems (89.54%). High seroprevalence was also observed in non-descript indigenous goats (85.04%), adult goat (69.62%), in does (67.46%) and goats infested with ticks (85.79%). The logistic model showed a gradient of increasing risk for commercial meat type Savanna (OR=3.681; CI=1.335-10.149) and non-descript indigenous (OR=3.466; CI=1.57-7.645) compared to Boer goats and for goats from the smallholder production system (OR=2.582; CI=1.182-5.639) and those with ticks (OR=3.587; CI=2.105-6.112). Results from this study showed that E. ruminantium infections were prevalent but were widely and unevenly distributed throughout South Africa. Findings from the study facilitate identification and mapping of risk areas for heartwater and its endeminicity in South Africa and should be taken into consideration for future disease control strategies and local goat improvement programs. PMID- 26829906 TI - The impact of event vividness, event severity, and prior paranormal belief on attributions towards a depicted remarkable coincidence experience: Two studies examining the misattribution hypothesis. AB - Two studies examine the impact event vividness, event severity, and prior paranormal belief has on causal attributions for a depicted remarkable coincidence experience. In Study 1, respondents (n = 179) read a hypothetical vignette in which a fictional character accurately predicts a plane crash 1 day before it occurs. The crash was described in either vivid or pallid terms with the final outcome being either severe (fatal) or non-severe (non-fatal). Respondents completed 29 causal attribution items, one attribution confidence item, nine scenario perception items, a popular paranormal belief scale, and a standard demographics questionnaire. Principal axis factoring reduced the 29 attribution items to four attribution factors which were then subjected to a 2 (event vividness) * 2 (event severity) * 2 (paranormal belief) MANCOVA controlling for respondent gender. As expected, paranormal believers attributed the accurate crash prediction less to coincidence and more to both paranormal and transcendental knowing than did paranormal sceptics. Furthermore, paranormal (psychokinesis) believers deemed the prediction more reflective of paranormal knowing to both (1) a vivid/non-fatal and (2) a pallid/fatal crash depiction. Vividness, severity, and paranormal belief types had no impact on attribution confidence. In Study 2, respondents (also n = 179) generated data that were a moderately good fit to the previous factor structure and replicated several differences across attributional pairings albeit for paranormal non-believers only. Corresponding effects for event severity and paranormal belief were not replicated. Findings are discussed in terms of their support for the paranormal misattribution hypothesis and the impact of availability biases in the form of both vividness and severity effects. Methodological issues and future research ideas are also discussed. PMID- 26829904 TI - Reproductive factors, hormone use and gastric cancer risk: The Singapore Chinese Health Study. AB - Gastric cancer incidence varies greatly worldwide, but is consistently twice as high in men than in women. The hormone-related factors hypothesized to be associated with lower risk of gastric cancer in women have not been fully explored in populations with a high background risk of gastric cancer. The Singapore Chinese Health Study (SCHS) is a prospective cohort study in which 34,022 of the participants enrolled between 1993 and 1998 were women between 45 and 74 years of age. Information on reproductive histories, hormone replacement therapy (HRT) and oral contraceptive (OC) use was collected through in-person interviews at baseline. As of December 31, 2013, 269 incident gastric cancer cases were identified. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate gastric cancer risk associations. Older age at natural menopause (>=55 versus <45 years: HR = 0.50, 95% CI: 0.25-0.99), type of menopause (other versus natural: HR = 0.48, 95% CI: 0.27-0.87) and greater years of menstrual cycling (fourth versus first quartile: HR = 0.67, 95% CI: 0.46-0.96) were associated with a decreased risk of gastric cancer. Ever use of OCs and HRT was also associated with reduced risk of gastric cancer; the multivariable-adjusted HRs (95% CIs) were 0.40 (0.17-0.90) for use of HRT >3 years and 0.67 (0.47-0.94) for ever use of OCs, compared with never use. Reproductive factors associated with a longer window of fertility and the use of exogenous hormones were shown to reduce gastric cancer development in a cohort of Chinese women with a high background risk of gastric cancer. PMID- 26829907 TI - Green synthesis of silver nanoparticles and characterization of their inhibitory effects on AGEs formation using biophysical techniques. AB - Advanced glycation end-products (AGEs) resulting from non-enzymatic glycation are one of the major factors implicated in secondary complications of diabetes. Scientists are focusing on discovering new compounds that may be used as potential AGEs inhibitors without affecting the normal structure and function of biomolecules. A number of natural and synthetic compounds have been proposed as AGE inhibitors. In this study, we investigated the inhibitory effects of AgNPs (silver nanoparticles) in AGEs formation. AgNPs (~30.5 nm) synthesized from Aloe Vera leaf extract were characterized using UV-Vis spectroscopy, energy-dispersive X-ray spectroscopy (EDX), high resolution-transmission electron microscopy, X-ray diffraction and dynamic light scattering (DLS) techniques. The inhibitory effects of AgNPs on AGEs formation were evaluated by investigating the degree of reactivity of free amino groups (lysine and arginine residues), protein-bound carbonyl and carboxymethyl lysine (CML) content, and the effects on protein structure using various physicochemical techniques. The results showed that AgNPs significantly inhibit AGEs formation in a concentration dependent manner and that AgNPs have a positive effect on protein structure. These findings strongly suggest that AgNPs may play a therapeutic role in diabetes-related complications. PMID- 26829910 TI - Helicopters and Hospitalizations: Getting the Primary Care That We Invest In. PMID- 26829909 TI - Dusky-like is required for epidermal pigmentation and metamorphosis in Tribolium castaneum. AB - Dusky-like (Dyl) is associated with the morphogenesis of embryonic denticle, adult sensory bristle and wing hair in Drosophila melanogaster. And whether Dyl involved in insect post-embryonic development and its signal transduction are poorly understood. Here, phylogenetic analysis revealed that dyl displayed one-to one orthologous relationship among insects. In Tribolium castaneum, dyl is abundantly expressed at the late embryonic stage. Tissue-specific expression analysis at the late adult stage illustrated high expression of dyl in the fat body and ovary. Knockdown of dyl resulted in the defects in larval epidermal pigmentation and completely blocked the transitions from larval to pupal and pupal to adult stages of T. castaneum. We further discovered that dyl RNAi phenotypes were phenocopied by blimp-1 or shavenbaby (svb) silencing, and dyl was positively regulated by blimp-1 through svb in T. castaneum. These results suggest that Dyl functions downstream of Blimp-1 through Svb for larval epidermal pigmentation and metamorphosis. Moreover, ftz-f1 was down-regulated after RNA interference (RNAi) suppressing any of those three genes, indicating that Ftz-f1 works downstream of Dyl to mediate the effects of Blimp-1, Svb and Dyl on metamorphosis in T. castaneum. This study provides valuable insights into functions and signaling pathway of insect Dyl. PMID- 26829911 TI - Should Patients Have Periodic Health Examinations?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center. AB - Physicians and patients have come to expect that periodic health examinations (PHEs) are a standard part of comprehensive ongoing medical care. However, considerable research has not demonstrated a substantial benefit of the PHE. Given this lack of benefit and the high total cost of PHE to the health care system, the American Board of Internal Medicine (ABIM) Foundation and the Society of General Internal Medicine (SGIM) have identified "routine health checks in asymptomatic patients" as something of low value that physicians and patients should question, as a part of the Choosing Wisely campaign. Two discussants review the debate about PHE and consider the value of PHE for a healthy 70-year old woman who appreciates seeing her physician annually. PMID- 26829913 TI - Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older: United States, 2016. PMID- 26829914 TI - Hepatitis C Virus Treatment and Persons Who Inject Drugs. PMID- 26829915 TI - Hepatitis C Virus Treatment and Persons Who Inject Drugs. PMID- 26829916 TI - Correction: Alexander Technique Lessons or Acupuncture Sessions for Persons With Chronic Neck Pain. PMID- 26829917 TI - Annals for Educators - 2 February 2016. PMID- 26829918 TI - Epilepsy. AB - This issue provides a clinical overview of epilepsy, focusing on diagnosis, prevention, treatment, and further considerations. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers. PMID- 26829919 TI - Web Exclusives. Annals Graphic Medicine: Atrial Flutter. PMID- 26829920 TI - MU-'Diving suit' for liquid-phase high-Q resonant detection. AB - A resonant cantilever sensor is, for the first time, dressed in a water-proof 'diving suit' for real-time bio/chemical detection in liquid. The MU-'diving suit' technology can effectively avoid not only unsustainable resonance due to heavy liquid-damping, but also inevitable nonspecific adsorption on the cantilever body. Such a novel technology ensures long-time high-Q resonance of the cantilever in solution environment for real-time trace-concentration bio/chemical detection and analysis. After the formation of the integrated resonant micro-cantilever, a patterned photoresist and hydrophobic parylene thin film are sequentially formed on top of the cantilever as sacrificial layer and water-proof coat, respectively. After sacrificial-layer release, an air gap is formed between the parylene coat and the cantilever to protect the resonant cantilever from heavy liquid damping effect. Only a small sensing-pool area, located at the cantilever free-end and locally coated with specific sensing material, is exposed to the liquid analyte for gravimetric detection. The specifically adsorbed analyte mass can be real-time detected by recording the frequency-shift signal. In order to secure vibration movement of the cantilever and, simultaneously, reject liquid leakage from the sensing-pool region, a hydrophobic parylene made narrow slit structure is designed surrounding the sensing-pool. The anti-leakage effect of the narrow slit and damping limited resonance Q-factor are modelled and optimally designed. Integrated with electro thermal resonance excitation and piezoresistive frequency readout, the cantilever is embedded in a micro-fluidic chip to form a lab-chip micro-system for liquid phase bio/chemical detection. Experimental results show the Q-factor of 23 in water and longer than 20 hours liquid-phase continuous working time. Loaded with two kinds of sensing-materials at the sensing-pools, two types of sensing chips successfully show real-time liquid-phase detection to ppb-level organophosphorous pesticide of acephate and E.coli DH5alpha in PBS, respectively. The proposed method fundamentally solves the long-standing problem of being unable to operate a resonant micro-sensor in liquid well. PMID- 26829921 TI - Cicca acida L.: phytochemistry and pharmacological studies. AB - OBJECTIVES: Cicca acida L., is reported with traditional and pharmacological uses, and a good number of pure compounds have been isolated from its different parts. But published information is sporadic and fragmentary in nature. Therefore, it is imperative to have a comprehensive account of all of its medicinal potentialities with critical analysis. In this review, the traditional reports, phytochemical and pharmacology studies associated with Cicca acida have been compiled to figure out the net possibilities for its application in modern medicine. KEY FINDINGS: Careful scrutiny reveals that the plant possesses a huge range of medicinal properties, but published report analysis suggests that the plant is effectively used as antibacterial, hepatoprotective, anticonceptive and antidiabetic purposes. The published papers revealed the bioactivity of only 04 compounds. This indicates that a good number of isolated major compounds of this plant are yet to be pharmacologically investigated. CONCLUSION: Intensive study of Cicca acida showed that despite of its plentiful isolated molecules, the effort leading to final product stage seems to be less. Therefore, the plant and its compounds need concentrated effort towards establishment of its therapeutic potentialities. PMID- 26829922 TI - Microbial glycolipoprotein-capped silver nanoparticles as emerging antibacterial agents against cholera. AB - BACKGROUND: With the increased number of cholera outbreaks and emergence of multidrug resistance in Vibrio cholerae strains it has become necessary for the scientific community to devise and develop novel therapeutic approaches against cholera. Recent studies have indicated plausibility of therapeutic application of metal nano-materials. Among these, silver nanoparticles (AgNPs) have emerged as a potential antimicrobial agent to combat infectious diseases. At present nanoparticles are mostly produced using physical or chemical techniques which are toxic and hazardous. Thus exploitation of microbial systems could be a green eco friendly approach for the synthesis of nanoparticles having similar or even better antimicrobial activity and biocompatibility. Hence, it would be worth to explore the possibility of utilization of microbial silver nanoparticles and their conjugates as potential novel therapeutic agent against infectious diseases like cholera. RESULTS: The present study attempted utilization of Ochrobactrum rhizosphaerae for the production of AgNPs and focused on investigating their role as antimicrobial agents against cholera. Later the exopolymer, purified from the culture supernatant, was used for the synthesis of spherical shaped AgNPs of around 10 nm size. Further the exopolymer was characterized as glycolipoprotein (GLP). Antibacterial activity of the novel GLP-AgNPs conjugate was evaluated by minimum inhibitory concentration, XTT reduction assay, scanning electron microscopy (SEM) and growth curve analysis. SEM studies revealed that AgNPs treatment resulted in intracellular contents leakage and cell lysis. CONCLUSION: The potential of microbially synthesized nanoparticles, as novel therapeutic agents, is still relatively less explored. In fact, the present study first time demonstrated that a glycolipoprotein secreted by the O. rhizosphaerae strain can be exploited for production of AgNPs which can further be employed to treat infectious diseases. Although this type of polymer has been obtained earlier from marine fungi and bacteria, none of these reports have studied the role of this polymer in AgNPs synthesis and its application in cholera therapy. Interestingly, the microbial GLP-capped AgNPs exhibited antibacterial activity against V. cholerae comparable to ciprofloxacin. Thus the present study may open up new avenues for development of novel therapeutic agents for treatment of infectious diseases. Graphical abstract Development of novel therapeutic agents for treatment of cholera. PMID- 26829923 TI - Efficacy and safety of Maekmoondong-tang for chronic dry cough: a study protocol for a randomized controlled trial. AB - BACKGROUND: Chronic cough, defined it lasts more than 8 weeks. The symptom is common, but highly troublesome, and it reduces quality of life. Despite much effort to develop a protocol for diagnosis and treatment of chronic cough, it remains problematic to determine its cause. As a result, treatment is often unsuccessful. Thus, there is much interest regarding the use of symptomatic drugs to control chronic cough. Maekmoondong-tang is widely used in East Asian countries to treat chronic dry cough. Several experimental studies have reported that the herbal medicine has immunomodulatory and antitussive effects. Clinical studies involving Maekmoondong-tang have also been carried out; however, these studies have involved treating various diseases as a whole rather than chronic cough itself. Thus, we aim to evaluate the efficacy and safety of Maekmoondong tang in chronic dry cough patients with a randomized controlled trial. METHODS/DESIGN: This study is designed as an exploratory, single-center, placebo controlled, double-blind, randomized, parallel group clinical trial. Patients with dry cough that has lasted more than 8 weeks will be recruited, after a 1 week run-in period, and randomly allocated to either the Maekmoondong-tang treatment group or the placebo group. The patients will receive Maekmoondong-tang or placebo granules 3 times daily for 4 weeks, with a 2-week follow-up. The primary outcome is a 10-point cough diary that will be recorded on a daily basis. The secondary outcomes comprise a cough visual analog scale, the Leicester Cough Questionnaire (Korean version), the Pattern Identification for Chronic Cough Questionnaire, biomarkers, safety testing, etc. Adverse events will also be reported. DISCUSSION: This trial will assess the efficacy and safety of Maekmoondong-tang in chronic dry cough. TRIAL REGISTRATION: Korean Clinical Trial Registry ( http://cris.nih.go.kr ; registration number: KCT0001646). Date of registration: October 5 2015. PMID- 26829924 TI - Trends in genital warts by socioeconomic status after the introduction of the national HPV vaccination program in Australia: analysis of national hospital data. AB - BACKGROUND: Human papillomavirus (HPV) vaccination targeting females 12-13 years commenced in Australia in 2007, with catch-up of females 13-26 years until the end of 2009. No analyses of HPV vaccination program impact by either socioeconomic or geographic factors have been reported for Australia. METHODS: Hospital admissions between July 2004-June 2011 involving a diagnosis of genital warts were obtained from a comprehensive national database. We compared sex- and age-specific admission rates in July 2006-June 2007 (pre-vaccination period) and July 2010-June 2011 (post-vaccination period) according to Index of Relative Socio-economic Disadvantage, nationally and stratified by remoteness area relating to the individual's area of residence, using Poisson/ negative binomial models. RESULTS: Admission rates per 100,000 population in females aged 10-19 years (predominantly vaccinated at school), reduced from 42.2 to 6.0 (rate reduction 86.7 %; 95 % CI:82.2-90.0 %) in more disadvantaged areas and from 26.8 to 4.0 (85.0 %; 95 % CI:79.7-88.9 %) in less disadvantaged areas. In females aged 20-29 years (predominantly vaccinated in the community), the decreases were from 73.9 to 26.4 (66.0 %; 95 % CI:57.7-72.6 %) and from 61.9 to 23.8 (61.6 %; 95 % CI:52.9-68.7 %) in more and less disadvantaged areas, respectively. The reductions were similar in more vs less disadvantaged areas both inside major cities (88.6 %; 95 % CI: 82.2-92.7 % vs 87.9 %; 95 % CI:82.6-91.6 % in females aged 10-19 years; 64.0 %; 95 % CI:57.0-69.9 % vs 63.8 %; 95 % CI:52.9-72.1 % for females aged 20-29 years) and outside major cities (88.8 %; 95 % CI: 83.7-92.3 % vs 85.8 %; 95 % CI:73.5-92.4 % in females aged 10-19 years; 71.1 %; 95 % CI:58.8 79.7 % vs 67.6 %; 95 % CI:48.2-79.8 % for females aged 20-29 years). Admission rates in males aged 20-29 years also reduced, by 23.0 % (95 % CI:4.8-37.8 %) and 39.4 % (95 % CI:28.9-48.3 %) in more versus less disadvantaged areas respectively. CONCLUSIONS: The relative reduction in genital warts appears similar in young females across different levels of disadvantage, including within and outside major cities, both for females predominantly vaccinated at school and in the community. PMID- 26829925 TI - Testicular length as an indicator of the onset of sperm production in alpacas under Swedish conditions. AB - BACKGROUND: The popularity of alpacas (Vicugna pacos) is increasing in Sweden as well as in other countries; however, knowledge about optimal management practices under Swedish conditions is still limited. The wide age range reported when the onset of puberty can occur, between 1 and 3 years of age, makes management decisions difficult and may be influenced by the conditions under which the alpacas are kept. The aim of this study was to find out when Swedish alpacas can be expected to start producing sperm, by using testicular length and body condition score as a more precise indirect indicator than age. RESULTS: This study suggests that animals with a testicular length >=3.8 cm would be producing sperm; however, if it is crucial to know that there is no sperm production for management purposes, the threshold level for testicular length used to differentiate between sperm-producing and non-sperm producing animals should be <=1.6 cm instead. If only one variable is considered, testicular length appears to better than age alone to predict sperm production. Body condition score together with testicular length explains the individual onset of puberty and better guide management recommendations. CONCLUSIONS: Using a combination of these parameters (testicular length, body condition score and age) as a tool for decision making for alpaca husbandry under Swedish conditions is suggested. PMID- 26829926 TI - Cochlear implant and congenital cholesteatoma. AB - BACKGROUND: The occurence of cholesteatoma and cochlear implant is rare. Secondary cholesteatomas may develop as a result of cochlear implant surgery. Primarily acquired cholesteatoma is not typically associated with congenital sensorineural hearing loss or cochlear implant in children. The occurrence of congenital cholesteatoma during cochlear implant surgery has never been reported before, partly because all patients are preoperatively submitted to imaging studies which can theoretically exclude the disease. CASE PRESENTATION: We have reported a rare case of congenital cholesteatoma, found during sequential second side cochlear implantation in a 3-year-old child. The child underwent a computed tomography (CT) scan and magnetic resonance imaging (MRI) at 12 months of age, before the first cochlear implant surgery, which excluded middle ear pathology. The mass was removed as an intact pearl, without visible or microscopic violation of the cholesteatoma capsule. All the areas where middle ear structures were touching the cholesteatoma were vaporized with a laser and the cochlear implant was inserted uneventfully. Further follow-up excluded residual disease. CONCLUSION: We believe that primary, single stage placement of a cochlear implant (CI) with simultaneous removal of the congenital cholesteatoma can be performed safely. However, to prevent recurrence, the capsule of the cholesteatoma must not be damaged and complete laser ablation of the surface, where suspicious epithelial cells could remain, is recommended. In our opinion, cholesteatoma removal and cochlear implantation should be staged if these conditions are not met, and/or the disease is at a more advanced stage. It is suspected, that the incidence of congenital cholesteatoma in pediatric CI candidates is much higher that in average pediatric population. PMID- 26829927 TI - A needs assessment of people living with diabetes and diabetic retinopathy. AB - BACKGROUND: The Kilimanjaro Diabetic Programme was initiated in response to the needs of people living with diabetes (PWLD) to identify barriers to uptake of screening for diabetic retinopathy, to improve management of diabetes, and establish an affordable, sustainable eye screening and treatment programme for diabetic retinopathy. Intervention Mapping was used as the framework for the needs assessment. METHODS: A mixed methods approach was used. Five psychometric measures, Diabetes Knowledge Questionnaire, Diabetes Health Beliefs, Self Efficacy scale, Problem Areas in Diabetes scale, and Hopkins Scale Checklist-25 and a structured interview relating to self-efficacy, addressing disclosure of living with diabetes and life-style changes were used to triangulate the quantitative findings. These were administered to 26 PWLD presenting to rural district hospitals. RESULTS: The interviewees demonstrated low levels of perceived stigma regarding disclosure of living with diabetes and high levels of self-efficacy in raising community awareness of diabetes, seeking on going treatment from Western medicine over traditional healers and in seeking care on sick days. Self-efficacy was high for adjusting diet, although comprehensive dietary knowledge was poor. Negative emotions expressed at diagnosis, changes in life style and altered quality of life were reflected in high levels of anxiety and depression. CONCLUSIONS: Low levels of stigma surrounding living with diabetes were linked to a desire to raise community awareness of diabetes, help others live with diabetes and to secure social support to access hospital services. Confusion over what constituted a healthy diet showed the importance of comprehensive, accessible diabetes education, essential to ensuring good glycaemic control, and preventing diabetic complications, including diabetic retinopathy. Low levels of self-efficacy along with high levels of anxiety and depression may have a negative impact on the uptake of screening for Diabetic Retinopathy. The findings of this needs assessment led to the planning and delivery of a comprehensive health intervention programme for PLWD in Kilimanjaro Region. The programme has provided them with support, resources, education, and screening for diabetic retinopathy at the regional hospital and at district level with mobile digital retinal cameras, an electronic diabetic database and computerised follow up to ensure continuity of care. PMID- 26829928 TI - Latin American Study of Nutrition and Health (ELANS): rationale and study design. AB - BACKGROUND: Obesity is growing at an alarming rate in Latin America. Lifestyle behaviours such as physical activity and dietary intake have been largely associated with obesity in many countries; however studies that combine nutrition and physical activity assessment in representative samples of Latin American countries are lacking. The aim of this study is to present the design rationale of the Latin American Study of Nutrition and Health/Estudio Latinoamericano de Nutricion y Salud (ELANS) with a particular focus on its quality control procedures and recruitment processes. METHODS/DESIGN: The ELANS is a multicenter cross-sectional nutrition and health surveillance study of a nationally representative sample of urban populations from eight Latin American countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru and Venezuela). A standard study protocol was designed to evaluate the nutritional intakes, physical activity levels, and anthropometric measurements of 9000 enrolled participants. The study was based on a complex, multistage sample design and the sample was stratified by gender, age (15 to 65 years old) and socioeconomic level. A small-scale pilot study was performed in each country to test the procedures and tools. DISCUSSION: This study will provide valuable information and a unique dataset regarding Latin America that will enable cross-country comparisons of nutritional statuses that focus on energy and macro- and micronutrient intakes, food patterns, and energy expenditure. TRIAL REGISTRATION: Clinical Trials NCT02226627. PMID- 26829929 TI - Complex Care Options for Patients With Advanced Heart Failure Approaching End of Life. AB - Care for patients with advanced cardiac disease continues to evolve in a complex milieu of therapeutic options, advanced technological interventions, and efforts at improving patient-centered care and shared decision-making. Despite improvements in quality of life and survival with these interventions, optimal supportive care across the advanced illness trajectory remains diverse and heterogeneous. Herein, we outline challenges in prognostication, communication, and caregiving in advanced heart failure and review the unique needs of patients who experience frequent hospitalizations, require chronic home inotropic support, and who have implantable cardioverter-defibrillators and mechanical circulatory support in situ, to name a few. PMID- 26829931 TI - Gene expression profiling of the green seed problem in Soybean. AB - BACKGROUND: Due to the climate change of the past few decades, some agricultural areas in the world are now experiencing new climatic extremes. For soybean, high temperatures and drought stress can potentially lead to the "green seed problem", which is characterized by chlorophyll retention in mature seeds and is associated with lower oil and seed quality, thus negatively impacting the production of soybean seeds. RESULTS: Here we show that heat and drought stress result in a "mild" stay-green phenotype and impaired expression of the STAY-GREEN 1 and STAY GREEN 2 (D1, D2), PHEOPHORBIDASE 2 (PPH2) and NON-YELLOW COLORING 1 (NYC1_1) genes in soybean seeds of a susceptible soybean cultivar. We suggest that the higher expression of these genes in fully mature seeds of a tolerant cultivar allows these seeds to cope with stressful conditions and complete chlorophyll degradation. CONCLUSIONS: The gene expression results obtained in this study represent a significant advance in understanding chlorophyll retention in mature soybean seeds produced under stressful conditions. This will open new research possibilities towards finding molecular markers for breeding programs to produce cultivars which are less susceptible to chlorophyll retention under the hot and dry climate conditions which are increasingly common in the largest soybean production areas of the world. PMID- 26829930 TI - Comorbidities in Heart Failure: Are There Gender Differences? AB - Compared to men, women with heart failure (HF) are often older, smoke less, and have more preserved ejection fraction (EF) and hypertensive HF rather than HF of ischemic etiology. Gender-stratified outcomes on comorbidities data in HF are scarce. Women have traditionally been underrepresented in HF trials. Although data suggest that overall prognosis may be better in women, they experience lower quality of life with greater functional impairment from HF compared to men. Gender differences have been reported for comorbid diabetes, chronic obstructive pulmonary disease, renal dysfunction, anemia, and depression and may explain gender disparity in outcomes. However, possible confounding of comorbidities with known prognostic determinants in HF (such as EF) as well as gender differences in the utilization of medical therapies obscures interpretation. In this review, we will explore the evidence for gender differences in non-cardiovascular comorbidities in HF. Our findings may guide clinicians to individualize HF care, according to best practice, in the hope of improving prognosis for this chronic and debilitating condition. PMID- 26829933 TI - Stereotactic versus conventional radiotherapy for pain reduction and quality of life in spinal metastases: study protocol for a randomized controlled trial. AB - BACKGROUND: Painful spinal metastases have been treated with conventional radiotherapy for decades, but one-third of the patients have insufficient pain relief after treatment and one-fifth need retreatment. Stereotactic radiotherapy is a method to increase the dose in the spinal metastases with a potentially longer lasting palliative effect without increasing the side effects of the treatment and thereby is expected to improve the quality of life significantly. METHODS/DESIGN: This study is a multicenter prospective randomized clinical trial comparing conventional radiotherapy (1 x 8 Gy) with stereotactic radiotherapy (1 x 20 Gy) for pain reduction and quality of life in patients with painful spinal metastases. A total of 386 patients will be randomized between the two treatment groups. Besides pain measured by the Dutch Brief Pain Inventory, quality of life and cost-effectiveness also will be measured. The primary outcome is pain reduction at 6 weeks after treatment. Secondary outcomes will be the time to pain response, duration of pain relief, health-related quality of life and toxicity, as well as cost-effectiveness. DISCUSSION: This study investigates whether stereotactic radiotherapy with dose escalation for symptomatic spinal metastases can lead to improved pain reduction as compared to conventional radiotherapy without an increase of treatment-related side effects. These results will contribute to the optimization and individualization of the treatment for the patient. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02407795 (March 31, 2015). PMID- 26829932 TI - Emerging Trends in Epigenetic Regulation of Nutrient Deficiency Response in Plants. AB - Diverse environmental stimuli largely affect the ionic balance of soil, which have a direct effect on growth and crop yield. Details are fast emerging on the genetic/molecular regulators, at whole-genome levels, of plant responses to mineral deficiencies in model and crop plants. These genetic regulators determine the root architecture and physiological adaptations for better uptake and utilization of minerals from soil. Recent evidence also shows the potential roles of epigenetic mechanisms in gene regulation, driven by minerals imbalance. Mineral deficiency or sufficiency leads to developmental plasticity in plants for adaptation, which is preceded by a change in the pattern of gene expression. Notably, such changes at molecular levels are also influenced by altered chromatin structure and methylation patterns, or involvement of other epigenetic components. Interestingly, many of the changes induced by mineral deficiency are also inheritable in the form of epigenetic memory. Unravelling these mechanisms in response to mineral deficiency would further advance our understanding of this complex plant response. Further studies on such approaches may serve as an exciting interaction model of epigenetic and genetic regulations of mineral homeostasis in plants and designing strategies for crop improvement. PMID- 26829934 TI - A comparative study of the amount of alpha-synuclein in ischemic stroke and Parkinson's disease. AB - In the present study, we detected the level of oligomeric form of alpha-synuclein in the red blood cells of ischemic stroke, Parkinson's disease, and normal people and compared the differences to assess the diagnosis potential of alpha-synuclein in ischemic stroke patients. 86 ischemic stroke, 100 PD, and 102 healthy cases were enrolled in the present study. Total protein amount in the red blood cells were quantified by BCA assay using spectrophotometer. Levels of oligomeric form of alpha-synuclein were characterized by a sandwich ELISA. Analysis of correlation analysis and receiver operating characteristic curve were conducted. Significant differences were detected in the levels of oligomeric forms of alpha synuclein in different samples' blood cells (P < 0.05); the levels of total protein in (188.1 +/- 33.9 mmol/L) healthy people were significantly higher than that of PD (147.7 +/- 45.0 mmol/L) and ischemic stroke groups (142.9 +/- 43.0 mmol/L) (P < 0.05). There was no correlation between the age of patients and level of alpha-synuclein (R (2) = 0.216 in ischemic stroke group and -0.104 in PD group) and the receiver operating characteristic curve analysis showed a high sensitivity of alpha-synuclein in discriminating ischemic stroke (sensitivity was 63.7 % and specificity was 9.6 %) and PD (sensitivity was 44.1 % and specificity was 12.5 %) patients from the controls. The levels of oligomeric form of alpha synuclein of red blood cells in ischemic stroke and Parkinson's disease patients were both significant higher than normal people. And the level of oligomeric form alpha-synuclein showed a potential for diagnosis of ischemic stroke in clinic. PMID- 26829935 TI - Neuroprotective effect of lignans extracted from Eucommia ulmoides Oliv. on glaucoma-related neurodegeneration. AB - Glaucoma is a progressive neurodegenerative disease, characterized by retinal ganglion cells (RGCs) and axon degeneration. The development of neuroprotective drug is required for improving the efficiency of glaucoma treatment. Eucommia ulmoides Oliv. has been used as a source of traditional medicine and as a beneficial health food. Lignans is one of the main bioactive components of Eucommia ulmoides. Here, we show that lignans protects RGCs against oxidative stress-induced injury in vitro. Moreover, lignans exerts neuroprotective effect on glaucoma-associated optic neuropathy in glaucomatous rats. Lignans treatment could improve oxidative stress response in RGCs and retinas of glaucomatous rats. Lignans plays an anti-oxidative stress role via the activation of AMPK signaling. This study provides evidence that lignans possesses protective effect on glaucoma associated optic neuropathy. Lignans might be an alternative for the prevention and treatment of glaucomatous neurodegeneration. PMID- 26829937 TI - Vanillic aldehydes for the one-pot synthesis of novel 2-oxo-1,2,3,4 tetrahydropyrimidines. AB - A small library of novel 2-oxo-1,2,3,4-tetrahydropyrimidines was synthesized via a one-pot multicomponent Biginelli reaction. Copper complex [Formula: see text] which was used for the first time as a homogeneous and heterogeneous catalyst, makes this a facile and efficient reaction at room temperature. All the obtained products fall out of the solution in pure form and are easily isolated via filtration in good-to-excellent yields. The molecular structure of one of the products, ethyl 6-methyl-2-oxo-4-(4[Formula: see text]-isopropoxy-3[Formula: see text]-methoxyphenyl) - 1,2,3,4 - tetrahydropyrimidine-5- carboxylate, has been determined by X-ray crystallography. All non-hydrogen atoms in the heterocyclic, six-membered ring are determined to be approximately coplanar. PMID- 26829936 TI - Antioxidative-oxidative balance in epilepsy patients on antiepileptic therapy: a prospective case-control study. AB - Oxidative stress has been implicated in various disorders, including epilepsy. The aim of this study was to investigate the oxidant and antioxidant status of patients with epilepsy using antiepileptic drugs regularly and to compare them with healthy subjects. We investigated serum catalase (CAT), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and xanthine oxidase (XO) levels in 58 epilepsy patients and 25 healthy controls. Patients were divided into polytherapy (n = 17) and monotherapy (n = 41) groups, and antioxidant status was compared between the two groups and controls. There was no significant difference between the patient and control groups in terms of age or gender (p > 0.05). The mean duration of illness in the patients was 14.8 years, and the mean duration of treatment was 11.4 years. Comparison of the patient and control groups in terms of oxidative stress and antioxidant defence parameters revealed significantly higher MDA, GSH-Px, XO and lower level of CAT, SOD levels (p < 0.05). There were no differences in CAT, MDA, GSH-Px or SOD levels between the monotherapy and polytherapy groups; but the XO level was higher in the monotherapy group (p < 0.05). Although the XO level was decreased by polytherapy, it was higher than in controls. Our study found significantly low level of antioxidants in patients with epilepsy as compared to control. Thus, antiepileptic treatment did not improve oxidative stress parameters. Furthermore, our results show that polytherapy does not change the situation as compared with monotherapy. Antioxidant replacement therapy may benefit these patients. PMID- 26829938 TI - Synthesis of multi-functionalized benzofurans through the condensation of ninhydrin and phenols using SSA as a recyclable heterogeneous acid catalyst. AB - A simple and efficient one-pot methodology has been developed for the synthesis of biologically important multi-functionalized 3-(2[Formula: see text] hydroxyaryl)-2-(2[Formula: see text]-carboxyphenyl)benzofurans using silica sulfuric acid (SSA) as a heterogeneous acid catalyst in DMF medium. The significant advantages of this methodology are the use of SSA as a recyclable solid acid catalyst, operational simplicity, easy availability of the starting materials, and good yield of the products with high atom-economy. PMID- 26829939 TI - Activity landscape analysis of novel 5alpha-reductase inhibitors. AB - Inhibitors of the enzyme 5[Formula: see text]-reductase (5aR) are promising therapeutic agents for the treatment of benign prostatic hyperplasia (BPH) and prostate cancer. The lack of structural data of the enzyme 5aR prompts the application of ligand-based approaches to systematically explore the activity landscape of 5aR inhibitors. As part of an effort to develop inhibitors of this enzyme for the treatment of BPH, herein we discuss a chemoinformatic-based analysis of the activity landscape of a novel set of 53 novel pregnane and androstene compounds. It was found that, in general, for each pair of compounds in the set, as the structure similarity of the compounds increases the corresponding potency difference decreases. These results are in agreement with an overall smooth activity landscape. However, two potent activity cliff generators were identified pointing to specific small structural changes that have a large impact on the inhibition of 5aR. PMID- 26829940 TI - LPS alters pattern of sickness behavior but does not affect glutathione level in aged male rats. AB - Behavioral symptoms of sickness, such as fever and motor activity are a coordinated set of changes that develop during infection. The aim of study was to compare the sickness behaviour (SB) in healthy old and young rats treated with pyrogenic dose of endotoxin and to check their glutathione level. Before experimentation male Wistar rats were selected according to standard body mass, motor activity, and white blood cells count. Intraperitoneal injection of lipopolysaccharide (LPS) from E. coli was used to provoke SB. The level of liver glutathione, interleukin (IL) -6, deep body temperature (Tb) and motor activity were measured. Glutathione level in old and young rats did not differ significantly. In both young and old rats LPS administration provoked fever (the mean value of Tb was 38.06 +/- 0.01 degrees C in old rats, and 38.19 +/- 0.06 degrees C in young rats). LPS injection affected night-time activity in both groups (12 h averages were 1.56 +/- 0.40 counts in old LPS-treated rats vs 2.74 +/- 0.53 counts in not-treated old rats and 3.44 +/- 0.60 counts for young LPS treated vs 4.28 +/- 0.57 counts for young not-treated rats). The injection of LPS provoked an elevation of plasma IL-6 concentration (from values below the lowest detectable standard in not-treated groups of animals to 6322.82 +/- 537.00 pg/mL in old LPS-treated rats and 7415.62 +/- 451.88 pg/mL in young LPS-treated rats). Based on these data, we conclude that good health of aged rats prevents decrease in the glutathione level. Old rats are still able to develop SB in response to pyrogenic dose of LPS, although its components have changed pattern compared to young animals. PMID- 26829941 TI - Microcavity arrays as an in vitro model system of the bone marrow niche for hematopoietic stem cells. AB - In previous studies human mesenchymal stromal cells (MSCs) maintained the "stemness" of human hematopoietic progenitor cells (HPCs) through direct cell cell contact in two-dimensional co-culture systems. We establish a three dimensional (3D) co-culture system based on a custom-made chip, the 3(D)-KITChip, as an in vitro model system of the human hematopoietic stem cell niche. This array of up to 625 microcavities, with 300 MUm size in each orientation, was inserted into a microfluidic bioreactor. The microcavities of the 3(D)-KITChip were inoculated with human bone marrow MSCs together with umbilical cord blood HPCs. MSCs used the microcavities as a scaffold to build a complex 3D mesh. HPCs were distributed three-dimensionally inside this MSC network and formed beta catenin- and N-cadherin-based intercellular junctions to the surrounding MSCs. Using RT(2)-PCR and western blots, we demonstrate that a proportion of HPCs maintained the expression of CD34 throughout a culture period of 14 days. In colony-forming unit assays, the hematopoietic stem cell plasticity remained similar after 14 days of bioreactor co-culture, whereas monolayer co-cultures showed increasing signs of HPC differentiation and loss of stemness. These data support the notion that the 3D microenvironment created within the microcavity array preserves vital stem cell functions of HPCs more efficiently than conventional co-culture systems. PMID- 26829942 TI - Exploring Uncertainty in Economic Evaluations of Drugs and Medical Devices: Lessons from the First Review of Manufacturers' Submissions to the French National Authority for Health. AB - OBJECTIVES: The objective of this paper was to evaluate how uncertainty has been accounted for in the cost-effectiveness analyses (CEAs) submitted by manufacturers to the French National Authority for Health (HAS) and to identify recurring concerns in these submissions. METHODS: We used a cross-sectional design to evaluate manufacturers' submissions from the beginning of the evaluation process in October 2013 to the end of May 2015 (n = 28). The sources of uncertainty attached to these CEAs were categorized and assessed. Relevant data were extracted independently by two assessors. RESULTS: Adherence to the HAS reference case was generally considered to be acceptable. Methodological uncertainty and parameter uncertainty were the sources of uncertainty that were most frequently explored by manufacturers. The quality of reporting of deterministic sensitivity analysis and probabilistic sensitivity analysis varied substantially across submissions, with a frequent lack of justification of the plausible range of parameter point estimates in 12 submissions (43 %). Structural uncertainty was explored much less frequently. Concerns related to omission of either important clinical events or relevant health states or extrapolation of the effects of the technology beyond the time horizon of the clinical trials were identified in 16 submissions (57 %). CONCLUSIONS: This study presented a characterization of the treatment of uncertainty for the first 28 manufacturers' submissions to the HAS. This work identified important concerns regarding the exploration of sources of uncertainty. The findings may help manufacturers to improve the quality of their submissions and may provide useful insights for extending guidelines on uncertainty analysis in CEAs submitted to the HAS. PMID- 26829943 TI - Reply to the critics on "binge drinking and alcohol prices". PMID- 26829945 TI - Fetal and neonatal imaging minisymposium--2015 executive summary. PMID- 26829946 TI - Guidelines for scanning twins and triplets with US and MRI. AB - Multiple-fetus gestations have an increased risk of discordant anomalies, aneuploidy and growth restriction compared to singleton pregnancies. In addition, twins sharing the same placenta are at risk for developing specific conditions that are potentially amenable to surgical management. In those scenarios, patients might need to be evaluated not only with US but with fetal MRI as well. This paper outlines basic guidelines to consider when imaging complicated multiple-fetus gestations during the 2nd and 3rd trimesters. PMID- 26829944 TI - Neuropsychological, Neurovirological and Neuroimmune Aspects of Abnormal GABAergic Transmission in HIV Infection. AB - The prevalence of HIV-associated neurocognitive disorders (HAND) remains high in patients with effective suppression of virus replication by combination antiretroviral therapy (cART). Several neurotransmitter systems were reported to be abnormal in HIV-infected patients, including the inhibitory GABAergic system, which mediates fine-tuning of neuronal processing and plays an essential role in cognitive functioning. To elucidate the role of abnormal GABAergic transmission in HAND, the expression of GABAergic markers was measured in 449 human brain specimens from HIV-infected patients with and without HAND. Using real-time polymerase chain reaction, immunoblotting and immunohistochemistry we found that the GABAergic markers were significantly decreased in most sectors of cerebral neocortex, the neostriatum, and the cerebellum of HIV-infected subjects. Low GABAergic expression in frontal neocortex was correlated significantly with high expression of endothelial cell markers, dopamine receptor type 2 (DRD2L), and preproenkephalin (PENK) mRNAs, and with worse performance on tasks of verbal fluency. Significant associations were not found between low GABAergic mRNAs and HIV-1 RNA concentration in the brain, the history of cART, or HIV encephalitis. Pathological evidence of neurodegeneration of the affected GABAergic neurons was not present. We conclude that abnormally low expression of GABAergic markers is prevalent in HIV-1 infected patients. Interrelationships with other neurotransmitter systems including dopaminergic transmission and with endothelial cell markers lend added support to suggestions that synaptic plasticity and cerebrovascular anomalies are involved with HAND in virally suppressed patients. PMID- 26829947 TI - Why do we need more data on MR volumetric measurements of the fetal lung? AB - Fetal lung hypoplasia is associated with a series of congenital anomalies, particularly the congenital diaphragmatic hernia. Evaluation of the severity of the lung hypoplasia is important for parental counseling, assessment of prognosis and planning of postnatal management. Although a large number of studies have been performed to measure fetal lung volumes in order to predict outcome, there are little data on fetuses younger than 24 weeks of gestation, the age when parental counseling is crucial if termination is considered. Few studies have evaluated prognosis of lung hypoplasia in fetuses with congenital chest anomalies other than congenital diaphragmatic hernia. We review the studies on measurements of the fetal lung volumes by MRI. PMID- 26829948 TI - Prenatal counseling tools for the pediatric radiologist as part of a multidisciplinary team. AB - Fetal abnormalities are present in 3-5% of all pregnancies, leading to increased anxiety and the need for important discussions between patients and their care providers. Regardless of the severity of the anomaly, receiving the information can be traumatic for the pregnant patient and her partner. Most physicians who aren't trained to provide prenatal counseling understandably feel uncomfortable with the uncertainty and complex issues that arise in such high-stress counseling sessions. Genetic counselors are specifically trained to counsel patients in the setting of a fetal abnormality; however additional input from pediatric radiologists and other pediatric specialists is invaluable to parents in these situations and such input is an essential part of a team approach to prenatal counseling. The goal of this article is to provide a basic approach to counseling in the prenatal setting for pediatric radiologists and other specialists. PMID- 26829952 TI - [OR minute myth : Guidelines for calculation of DRG revenues per OR minute]. AB - The economic situation in German Hospitals is tense and needs the implementation of differentiated controlling instruments. Accordingly, parameters of revenue development of different organizational units within a hospital are needed. This is particularly necessary in the revenue and cost-intensive operating theater field. So far there are only barely established productivity data for the control of operating room (OR) revenues during the year available. This article describes a valid method for the calculation of case-related revenues per OR minute conform to the diagnosis-related groups (DRG).For this purpose the relevant datasets from the OR information system and the S 21 productivity report (DRG grouping) of the University Medical Center Gottingen were combined. The revenues defined in the DRG browser of the Institute for Hospital Reimbursement (InEK) were assigned to the corresponding process times--incision-suture time (SNZ), operative preparation time and anesthesiology time--according to the InEK system. All full time stationary DRG cases treated within the OR were included and differentiated according to the surgical department responsible. The cost centers "OR section" and "anesthesia" were isolated to calculate the revenues of the operating theater. SNZ clusters and cost type groups were formed to demonstrate their impact on the revenues per OR minute. A surgical personal simultaneity factor (GZF) was calculated by division of the revenues for surgeons and anesthesiologists. This factor resembles the maximum DRG financed personnel deployment for surgeons in German hospitals.The revenue per OR minute including all cost types and DRG was 16.63 ?/min. The revenues ranged from 10.45 to 24.34 ?/min depending on the surgical field. The revenues were stable when SNZ clusters were analyzed. The differentiation of cost type groups revealed a revenue reduction especially after exclusion of revenues for implants and infrastructure. The calculated GZF over all surgical departments was 2.2 (range 1.9-3.6). A calculation of this factor at the DRG level can give economically relevant information about the case-related personnel deployment.This analysis shows for the first time the DRG-conform calculation of revenues per OR minute. There is a strong dependency on the considered cost type and the performing surgical field. Repetitive analyses are necessary due to the lack of reference values and are a suitable tool to monitor the revenue development after measures for process optimization. Comparative analyses within different surgical fields on this data base should be avoided. The demonstrated method can be used as a guideline for other hospitals to calculate the DRG revenues within the OR. This enables pursuing cost-effectiveness analysis by comparing these revenues with cost data from the cost unit accounting at a DRG or case level. PMID- 26829949 TI - Three-dimensional ultrasound of the fetus: how does it help? AB - Three-dimensional ultrasonography (3-D US) was introduced to the field of fetal imaging in the early 1990s. Since then several publications have described potential applications for the diagnosis of congenital malformations as well as organ volumetry. This article reviews basic principles of 3-D US as well as its clinical applicability to prenatal diagnosis of abnormalities involving the face, spine and skeletal system, as well as potential applications of 3-D US for fetal cardiovascular and neuroimaging. Limitations related to motion artifacts, acoustic shadowing and barriers to clinical implementation of 3-D US in clinical practice are addressed. PMID- 26829954 TI - Attenuation correction in stress-only myocardial perfusion imaging. PMID- 26829953 TI - [Anesthesiological management of elderly trauma patients]. AB - BACKGROUND: The demographic change is accompanied by an increasing number of elderly trauma patients. Geriatric patients with trauma often show several comorbidities and as a result have a high perioperative risk to develop postoperative morbidity and mortality. The 30-day mortality is high. AIM: This article presents an overview of the perioperative management of elderly trauma patients in order to improve the perioperative outcome of these high risk patients. MATERIAL AND METHODS: A literature search was carried out focusing on the latest developments in the field of elderly trauma patients in order to present guidance on preoperative, intraoperative and postoperative anesthesiological management. RESULTS: Elderly trauma patients should undergo operative interventions as soon as possible. Many of these patients have a high risk profile. This can be estimated using risk scores in order to allow a prognosis for the outcome of patients. The informed consent needs to be discussed accordingly. The perioperative management is ideally addressed in a multidisciplinary approach. An array of questions in perioperative management, such as the mode of anesthesia, the ideal individual transfusion trigger and fluid management have not yet been adequately addressed in studies. CONCLUSION: The level of evidence in the perioperative management of elderly trauma patients is poor; therefore, there is an urgent need for large prospective studies in order to define uniform standards and guidelines. PMID- 26829955 TI - Cardiovascular disease in the literature: A selection of recent original research papers. PMID- 26829957 TI - Zika vaccine could be in production by year's end, says maker. PMID- 26829956 TI - Vasodilator stress agents for myocardial perfusion imaging. PMID- 26829958 TI - Assessment of Possible Drug Interactions in Patients with Psoriasis and Associated Comorbid Medical Conditions: An Observational Study. AB - BACKGROUND: Associated co-morbidities with psoriasis are treated with concomitant medications apart from the antipsoriatic therapy and the resulting Drug-Drug Interactions (DDI) may affect therapeutic outcome. OBJECTIVE: To assess the DDI in psoriatic patients with co-morbidities. METHOD: In this prospective observational analysis, 150 prescriptions of psoriatic patients, receiving two or more drugs were analysed using drug interaction checker software. DDI was classified into minor, moderate, major and pharmacokinetic & pharmacodynamic. RESULT: Of 150 patients, 77.3% (n=116) had cardiovascular comorbities; diabetes mellitus (49.3%), psoriatic arthritis (20.7%), hyperlipidemia (46%), infections (28.7%), neurologic conditions (24.7%) and dermatologic conditions (37.3%) were other reported comorbidities. Of these, 138 (92%) patients had 612 DDI (4.49 interactions/patient). More number of interactions were seen in 45-60 yrs (n=311, 50.8%). Moderate DDI (79.9%) were higher; 306 (50%) were pharmacokinetic interactions. Frequent interactions were due to non-steroidal anti-inflammatory drugs (n=229, 37.4%) and antibiotics (n=176, 28.8%). Monitoring of the signs & symptoms was the advised intervention in 67.2% of patients. Mean DDI per patient was more in those who received >10 drugs (9.67). There was an increased number of DDI with an increase in the number of medications which was statistically significant (p<0.01), with greater number of (n=458, 74.8%) interactions seen in those who received 5-10 drugs. CONCLUSION: There was an increased number of DDI in those who received more number of drugs. Careful monitoring with appropriate timely laboratory investigations, and a rational drug prescription for the comorbid conditions can prevent the occurrence of harmful DDIs. PMID- 26829960 TI - Refractory Otitis Media and Sinonasal Disease in a Child. PMID- 26829959 TI - Management of Infectious Aspects of Atopic Dermatitis in Primary Care: A Resident Survey. AB - Atopic dermatitis (AD) is the most common skin disease encountered by pediatric primary care providers. To describe the knowledge, attitudes, and practices of primary care residents in the management of infectious aspects of pediatric AD, an anonymous web-based survey was offered to all residents in the pediatric and family medicine departments at 3 New York City hospitals. Eighty residents responded. Most (62%) reported seeing 5 to 14 patients with AD monthly. Twenty seven percent reported obtaining cultures prior to prescribing oral antibiotics most of the time, while 8% reported doing so before giving topical antibiotics. Most respondents (60%) reported never/rarely recommending dilute bleach baths, and family medicine residents were significantly more likely to report never doing so (67% vs 16%, P < .001). Greater education on the use of cultures to guide treatment and potential benefits of dilute bleach baths is needed, especially given increasing antibiotic resistance. PMID- 26829962 TI - A rare medley: concurrent ipsilateral femur head and neck fracture without hip dislocation. AB - Simultaneous post-traumatic ipsilateral fracture of femur head and subcapital femur neck without hip dislocation is a rare presentation and easily missed on X ray imaging. A 48 years old male, with a history of high-energy road traffic accident, presented to us with severe pain in the left hip region and inability to ambulate. Preliminary X-ray showed impacted subcapital fracture with varus angulation between femur head and neck. Further computed tomography (CT) scan imaging showed ipsilateral fracture of femur head and subcapital femur neck without hip dislocation. Primary total hip arthroplasty was performed. Presently patient is 5 years post-surgery and can ambulate without support. In conclusion, this fracture pattern, though rare, should be suspected in high-energy road traffic accident patients with shear forces acting at femur neck. It can best be diagnosed using 3D CT scan imaging. Primary total hip arthroplasty is an appropriate treatment in such patients. PMID- 26829961 TI - Jejunal diverticulosis: a rare case of intestinal obstruction. AB - Small bowel diverticulosis represents an uncommon pathology that is often misdiagnosed, since it causes non-specific gastrointestinal symptoms. It is defined by the existence of multiple diverticula, which are located most frequently in the jejunum. Diagnosis often occurs following the presentation of related complications such as diverticulitis, haemorrhage, perforation or obstruction. Intestinal obstruction can be caused by inflammatory stenosis due to repeated episodes of diverticulitis, volvulus, intussusception or the presence of enteroliths. Here, we report a case of multiple jejunal diverticula causing acute intestinal obstruction. PMID- 26829963 TI - Arteriovenous fistula of the groin in a drug abuser with endocarditis. AB - Intravenous drug abusers commonly develop endocarditis due to injection of particulate matter that can cause endothelial damage to the valves. The frequent need to access the venous system can result in vascular traumas with potential complications including arteriovenous (AV) fistulas. Here, we present the case of an intravenous drug abuser with endocarditis and an unusually large AV fistula in the groin. The patient was successfully operated for endocarditis. However, the AV fistula was at the time not acknowledged. The combination of ileofemoral vein thrombosis and a large AV fistula led to pulmonary septic embolism and life threating, right-sided heart failure. Computed tomography scan did not reveal the AV fistula, but suspicion was raised. Ultrasound diagnosed and revealed the magnitude of the AV fistula, and the patient was treated with a minimally invasive percutaneous technique. PMID- 26829964 TI - Immune response to PCV2 vaccination in PRRSV viraemic piglets. PMID- 26829965 TI - NetF-positive Clostridium perfringens in neonatal foal necrotising enteritis in Kentucky. PMID- 26829966 TI - Axillary temperature measurement: a less stressful alternative for hospitalised cats? AB - Rectal temperature measurement (RTM) can promote stress and defensive behaviour in hospitalised cats. The aim of this study was to assess if axillary temperature measurement (ATM) could be a reliable and less stressful alternative for these animals. In this prospective study, paired rectal and axillary temperatures were measured in 42 cats, either by a veterinarian or a student. To assess the impact of these procedures on the cat's stress state, their heart rate was checked and a cat stress score (CSS) was defined and graded from 1 (relaxed) to 5 (terrified). A moderate correlation was found between RTM and ATM (r=0.52; P<0.0001). RTM was on average 0.9 degrees C (1.6 degrees F) higher than ATM (P<0.0001), although a wide variation was found in the difference between these two measurements (-2.1 degrees C to 3.6 degrees C (-3.8 degrees F to 6.5 degrees F)). ATM failed to identify hypothermia in 25 per cent of the cases and hyperthermia in 19 per cent of the cases but may be considered less stressful than RTM. Indeed, RTM induced a mildly greater increase in heart rate (+6 bpm; P=0.01) and in CSS (+0.2; P=0.001) than ATM. The results were not affected by operator type. In conclusion, RTM should remain the standard method to obtain accurate temperatures in cats. PMID- 26829967 TI - Effect upon biocompatibility and biocorrosion properties of plasma electrolytic oxidation in trisodium phosphate electrolytes. AB - Surface modification to improve the corrosion resistance and biocompatibility of the Mg-Al-Zn-Ca alloy was conducted via plasma electrolytic oxidation (PEO) in an electrolyte that included phosphate. Calcium phosphate can be easily induced on the surface of a PEO coating that includes phosphate in a physiological environment because Ca(2+) ions in body fluids can be combined with PO4 (3-). Cytotoxicity of the PEO coating formed in electrolytes with various amounts of Na3PO4 was identified. In particular, the effects that PEO films have upon oxidative stress and differentiation of osteoblast activity were studied. As the concentration of Na3PO4 in the electrolyte increased, the oxide layer was found to become thicker, which increased corrosion resistance. However, the PEO coating formed in electrolytes with over 0.2 M of added Na3PO4 exhibited more microcracks and larger pores than those formed in smaller Na3PO4 concentrations owing to a large spark discharge. A nonuniform oxide film that included more phosphate caused more cytotoxicity and oxidative stress, and overabundant phosphate content in the oxide layer interrupted the differentiation of osteoblasts. The corrosion resistance of the magnesium alloy and the thickness of the oxide layer were increased by the addition of Na3PO4 in the electrolyte for PEO treatment. However, excessive phosphate content in the oxide layer led to oxidative stress, which resulted in reduced cell viability and activity. PMID- 26829968 TI - Changes in the molecular ion yield and fragmentation of peptides under various primary ions in ToF-SIMS and matrix-enhanced ToF-SIMS. AB - Time of flight secondary ion mass spectrometry (ToF-SIMS) is a powerful technique for the nanoanalysis of biological samples, but improvements in sensitivity are needed in order to detect large biomolecules, such as peptides, on the individual cell level at physiological concentrations. Two promising options to improve the sensitivity of SIMS to large peptides are the use of cluster primary ions to increase desorption of intact molecules or the use of matrix-assisted laser desorption/ionization (MALDI) matrices to increase the ionization probability. In this paper, the authors have combined these two approaches in order to improve understanding of the interaction between ionization and fragmentation processes. The peptides bradykinin and melittin were prepared as neat monolayers on silicon, in a Dextran-40 matrix and in two common MALDI matrices, 2,5-dihydroxybenzoic acid (DHB) and alpha-cyano-4-hydroxy cinnamic acid (HCCA). ToF-SIMS spectra of these samples were collected using a range of small Bi cluster primary ions and large Ar cluster primary ions. The trends observed in the molecular ion yield and the [M+H](+)/C4H8N(+) ratio with primary ion cluster size were sample system dependent. The molecular ion yield of the bradykinin was maximized by using 30 keV Bi3 (+) primary ions in a DHB matrix but in the HCCA matrix, the maximum molecular ion yield was obtained by using 30 keV Bi7 (+) primary ions. In contrast, the molecular ion yield for melittin in both matrices was greatest using 20 keV Ar2000 (+) primary ions. Improvements in the molecular ion yield were only loosely correlated with a decrease in small fragment ions. The data indicate a complex interplay between desorption processes and ion formation processes which mean that the optimal analytical conditions depend on both the target analyte and the matrix. PMID- 26829969 TI - Substituent-Controlled Chemoselective Cleavage of C?C or Csp(2)-C(CO) Bond in alpha,beta-Unsaturated Carbonyl Compounds with H-Phosphonates Leading to beta Ketophosphonates. AB - An unprecedented substituent-controlled chemoselective cleavage of C?C double bond or C(sp(2))-C(CO) bond along with aerobic phosphorylation of alpha,beta unsaturated carbonyl compounds with H-phosphonates through a radical process has been disclosed. The current strategy provides an access to beta-ketophosphonates under mild conditions with a wide substrate scope. PMID- 26829970 TI - Family-to-work spillover and appraisals of caregiving by employed women caring for their elderly parents in Japan. AB - We examined the differences in family-to-work spillover between employed women who did and did not have caregiving responsibilities for elderly parents and the relationship between family-to-work spillover and negative and positive appraisals of caregiving using moderation analysis. A cross-sectional survey was conducted with middle-aged employed women (age >=40 years) from four large companies. Negative and positive family-to-work spillover (FWNS and FWPS, respectively) and negative and positive appraisals of caregiving were measured. Data from 386 non-caregivers and 82 caregivers were analyzed using Fisher's exact tests, Welch's t-tests, and hierarchical multiple regression. Results showed that FWNS was higher in caregivers than in non-caregivers, while there was no significant difference in FWPS. Caregiver "fulfillment from the caregiving role" (a subscale of positive appraisal) buffered the effects of caregiver "feelings of social restriction" (a subscale of negative appraisal) on FWNS. On the other hand, caregiver "commitment to caregiving tasks" (another positive subscale) intensified the effects of "feelings of social restriction" on FWNS. However, there was no relationship between negative and positive appraisals of caregiving and FWPS. These findings suggest that both negative and positive appraisals of caregiving are important contributors to FWNS among employed women caring for their parents. PMID- 26829971 TI - The influence of vibration on seated human drowsiness. AB - Although much is known about human body vibration discomfort, there is little research data on the effects of vibration on vehicle occupant drowsiness. A laboratory experimental setup has been developed. Vibration was applied to the volunteers sitting on the vehicle seat mounted on the vibration platform. Seated volunteers were exposed to a Gaussian random vibration, with 1-15 Hz frequency bandwidth at 0.2 ms(-2) r.m.s., for 20-minutes. Two drowsiness measurement methods were used, Psychomotor Vigilance Test (PVT) and Karolinska Sleepiness Scale (KSS). Significant changes in PVT (p<0.05) and KSS (p<0.05) were detected in all eighteen volunteers. Furthermore, a moderate correlation (r>0.4) was observed between objective measurement (PVT) and subjective measurement (KSS). The results suggest that exposure to vibration even for 20-minutes can cause significant drowsiness impairing psychomotor performance. This finding has important implications for road safety. PMID- 26829972 TI - Psychological detachment from work during non-work time: linear or curvilinear relations with mental health and work engagement? AB - This study examined whether a higher level of psychological detachment during non work time is associated with better employee mental health (Hypothesis 1), and examined whether psychological detachment has a curvilinear relation (inverted U shaped pattern) with work engagement (Hypothesis 2). A large cross-sectional Internet survey was conducted among registered monitors of an Internet survey company in Japan. The questionnaire included scales for psychological detachment, employee mental health, and work engagement as well as for job characteristics and demographic variables as potential confounders. The hypothesized model was tested with moderated structural equation modeling techniques among 2,234 respondents working in the tertiary industries with regular employment. Results showed that psychological detachment had curvilinear relations with mental health as well as with work engagement. Mental health improved when psychological detachment increased from a low to higher levels but did not benefit any further from extremely high levels of psychological detachment. Work engagement showed the highest level at an intermediate level of detachment (inverted U-shaped pattern). Although high psychological detachment may enhance employee mental health, moderate levels of psychological detachment are most beneficial for his or her work engagement. PMID- 26829973 TI - Cultural leisure activities, recovery and work engagement among hospital employees. AB - This study explored the relationship between cultural leisure activities, recovery experiences and two outcomes among hospital workers. The differences in recovery experiences (detachment, relaxation, mastery and control) and outcomes (work engagement and subjective recovery state) among hospital personnel (N=769) were analysed by the type (receptive or creative) and frequency of cultural activities. The cross-sectional data were collected by a digital questionnaire. Employees who reported both receptive and creative cultural leisure activities on a weekly basis had the highest relaxation, mastery and control experiences during off-job time. In addition, those with weekly creative activities had beneficial mastery experiences. There were no differences in recovery outcomes after adjustment for age, except in work engagement. Cultural leisure activities, and creative activities in particular, play an important role in certain aspects of recovery. PMID- 26829974 TI - Potential risk factors for onset of severe neck and shoulder discomfort (Katakori) in urban Japanese workers. AB - Katakori is a Japanese word, and there is no clear English translation. Katakori consists of two terms, Kata means neck and shoulder, kori means stiffness. Consequently, Katakori is defined as neck and shoulder discomfort or dull pain. Katakori is a major somatic complaint and has a large impact on workers. To examine the association between onset of severe Katakori and potential risk factors in Japanese workers, a prospective cohort study, entitled "Cultural and Psychosocial Influence on Disability (CUPID)", was conducted. Self-administered questionnaires were distributed twice: at baseline and 1 year after baseline. Logistic regression was used to explore the risk factors of onset of severe Katakori. Of those 1,398, the incidence of severe Katakori onset after 1 year was 3.0% (42 workers). Being female (adjusted odds ratio: 2.39, 95% confidence interval: 1.18-4.86), short sleep duration (adjusted odds ratio: 2.86, 95% confidence interval: 1.20-6.82) and depressed mood with some issues at work (adjusted odds ratio: 3.11, 95% confidence interval: 1.38-7.03) were significantly associated with onset of severe Katakori. Psychosocial factors as well as gender difference were associated with onset of severe Katakori. We suggest that mental health support at the workplace is important to prevent severe Katakori. PMID- 26829975 TI - Failure of the human lumbar motion-segments resulting from anterior shear fatigue loading. AB - An in-vitro experiment was designed to investigate the mode of failure following shear fatigue loading of lumbar motion-segments. Human male lumbar motion segments (age 32-42 years, n=6) were immersed in Ringer solution at 37 degrees C and repeatedly loaded, using a modified materials testing machine. Fatigue loading consisted of a sinusoidal shear load from 0 N to 1,500 N (750 N+/-750 N) applied to the upper vertebra of the motion-segment, at a frequency of 5 Hz. During fatigue experiments, several failure events were observed in the dynamic creep curves. Post-test x-ray, CT and dissection revealed that all specimens had delamination of the intervertebral disc. Anterior shear fatigue predominantly resulted in fracture of the apophyseal processes of the upper vertebrae (n=4). Exposure to the anterior shear fatigue loading caused motion-segment instability and resulted in vertebral slip corresponding to grade I and 'mild' grade II spondylolisthesis, as observed clinically. PMID- 26829976 TI - Mechanical intervention for reducing dust concentration in traditional rice mills. AB - A huge number of workers are employed in traditional rice mills where they are potentially exposed to dust. In this study a dust collection system was developed to capture the airborne dust in the rice mill. The feeding and sieving section of the mill was identified as major dust creating zone. The dust was captured by creating suitable air stream at feeding and sieving sections of the mill and collected in cyclone dust collector. The air stream was created by blower which was selected on the basis to get minimum air speed of 0.5 m/s in the working zones of workers. It was observed that the developed system is successfully collects the significant amount of dust and able to reduce the dust concentration up to 58%. Further, the respirable dust concentration reduced to below 5 mg/m(3) throughout the mill which is within the recommended limit of dust exposure. PMID- 26829977 TI - Test-retest reliability at the item level and total score level of the Norwegian version of the Spinal Cord Injury Falls Concern Scale (SCI-FCS). AB - OBJECTIVES: Translation of the Spinal Cord Injury Falls Concern Scale (SCI-FCS), and investigation of test-retest reliability on item-level and total-score-level. DESIGN: Translation, adaptation and test-retest study. SETTING: A specialized rehabilitation setting in Norway. PARTICIPANTS: Fifty-four wheelchair users with a spinal cord injury. The median age of the cohort was 49 years, and the median number of years after injury was 13. Interventions/measurements: The SCI-FCS was translated and back-translated according to guidelines. Individuals answered the SCI-FCS twice over the course of one week. We investigated item-level test-retest reliability using Svensson's rank-based statistical method for disagreement analysis of paired ordinal data. For relative reliability, we analyzed the total score-level test-retest reliability with intraclass correlation coefficients (ICC2.1), the standard error of measurement (SEM), and the smallest detectable change (SDC) for absolute reliability/measurement-error assessment and Cronbach's alpha for internal consistency. RESULTS: All items showed satisfactory percentage agreement (>=69%) between test and retest. There were small but non-negligible systematic disagreements among three items; we recovered an 11-13% higher chance for a lower second score. There was no disagreement due to random variance. The test-retest agreement (ICC2.1) was excellent (0.83). The SEM was 2.6 (12%), and the SDC was 7.1 (32%). The Cronbach's alpha was high (0.88). CONCLUSION: The Norwegian SCI-FCS is highly reliable for wheelchair users with chronic spinal cord injuries. PMID- 26829978 TI - Evidence-based vaccination strategies in obstetrics and gynecology settings: Current practices and methods for assessment. AB - Obstetrician-gynecologists have the potential to play an important role in the delivery of immunizations to women. However, despite national recommendations, immunization rates among pregnant women and adults in general remain low. Pragmatic immunization delivery trials are needed to demonstrate how best to deliver vaccines in such settings. We report the development and implementation of 2 novel methodologies for immunization delivery research and quality improvement in such settings. The first was the development and application of a 47-point Immunization Delivery Scale that formally assessed variability among practices in their engagement in a variety of evidence-based practices for improving immunization rates. The second was a covariate-constrained randomization technique - a method for achieving balance between study arms in cluster-randomized trials that is especially applicable to pragmatic trials.. To best achieve meaningful and interpretable findings, we recommend use of these or similar techniques in future immunization research and quality improvement projects in OB/GYN settings. PMID- 26829979 TI - The DELLA Protein SLR1 Integrates and Amplifies Salicylic Acid- and Jasmonic Acid Dependent Innate Immunity in Rice. AB - Gibberellins are a class of tetracyclic plant hormones that are well known to promote plant growth by inducing the degradation of a class of nuclear growth repressing proteins, called DELLAs. In recent years, GA and DELLAs are also increasingly implicated in plant responses to pathogen attack, although our understanding of the underlying mechanisms is still limited, especially in monocotyledonous crop plants. Aiming to further decipher the molecular underpinnings of GA- and DELLA-modulated plant immunity, we studied the dynamics and impact of GA and DELLA during infection of the model crop rice (Oryza sativa) with four different pathogens exhibiting distinct lifestyles and infection strategies. Opposite to previous findings in Arabidopsis (Arabidopsis thaliana), our findings reveal a prominent role of the DELLA protein Slender Rice1 (SLR1) in the resistance toward (hemi)biotrophic but not necrotrophic rice pathogens. Moreover, contrary to the differential effect of DELLA on the archetypal defense hormones salicylic acid (SA) and jasmonic acid (JA) in Arabidopsis, we demonstrate that the resistance-promoting effect of SLR1 is due at least in part to its ability to boost both SA- and JA-mediated rice defenses. In a reciprocal manner, we found JA and SA treatment to interfere with GA metabolism and stabilize SLR1. Together, these findings favor a model whereby SLR1 acts as a positive regulator of hemibiotroph resistance in rice by integrating and amplifying SA- and JA-dependent defense signaling. Our results highlight the differences in hormone defense networking between rice and Arabidopsis and underscore the importance of GA and DELLA in molding disease outcomes. PMID- 26829980 TI - AtKC1 and CIPK23 Synergistically Modulate AKT1-Mediated Low-Potassium Stress Responses in Arabidopsis. AB - In Arabidopsis (Arabidopsis thaliana), the Shaker K(+) channel AKT1 conducts K(+) uptake in root cells, and its activity is regulated by CBL1/9-CIPK23 complexes as well as by the AtKC1 channel subunit. CIPK23 and AtKC1 are both involved in the AKT1-mediated low-K(+) (LK) response; however, the relationship between them remains unclear. In this study, we screened suppressors of low-K(+) sensitive [lks1 (cipk23)] and isolated the suppressor of lks1 (sls1) mutant, which suppressed the leaf chlorosis phenotype of lks1 under LK conditions. Map-based cloning revealed a point mutation in AtKC1 of sls1 that led to an amino acid substitution (G322D) in the S6 region of AtKC1. The G322D substitution generated a gain-of-function mutation, AtKC1(D), that enhanced K(+) uptake capacity and LK tolerance in Arabidopsis. Structural prediction suggested that glycine-322 is highly conserved in K(+) channels and may function as the gating hinge of plant Shaker K(+) channels. Electrophysiological analyses revealed that, compared with wild-type AtKC1, AtKC1(D) showed enhanced inhibition of AKT1 activity and strongly reduced K(+) leakage through AKT1 under LK conditions. In addition, phenotype analysis revealed distinct phenotypes of lks1 and atkc1 mutants in different LK assays, but the lks1 atkc1 double mutant always showed a LK sensitive phenotype similar to that of akt1 This study revealed a link between CIPK-mediated activation and AtKC1-mediated modification in AKT1 regulation. CIPK23 and AtKC1 exhibit distinct effects; however, they act synergistically and balance K(+) uptake/leakage to modulate AKT1-mediated LK responses in Arabidopsis. PMID- 26829981 TI - Nitric Oxide, Ethylene, and Auxin Cross Talk Mediates Greening and Plastid Development in Deetiolating Tomato Seedlings. AB - The transition from etiolated to green seedlings involves the conversion of etioplasts into mature chloroplasts via a multifaceted, light-driven process comprising multiple, tightly coordinated signaling networks. Here, we demonstrate that light-induced greening and chloroplast differentiation in tomato (Solanum lycopersicum) seedlings are mediated by an intricate cross talk among phytochromes, nitric oxide (NO), ethylene, and auxins. Genetic and pharmacological evidence indicated that either endogenously produced or exogenously applied NO promotes seedling greening by repressing ethylene biosynthesis and inducing auxin accumulation in tomato cotyledons. Analysis performed in hormonal tomato mutants also demonstrated that NO production itself is negatively and positively regulated by ethylene and auxins, respectively. Representing a major biosynthetic source of NO in tomato cotyledons, nitrate reductase was shown to be under strict control of both phytochrome and hormonal signals. A close NO-phytochrome interaction was revealed by the almost complete recovery of the etiolated phenotype of red light-grown seedlings of the tomato phytochrome-deficient aurea mutant upon NO fumigation. In this mutant, NO supplementation induced cotyledon greening, chloroplast differentiation, and hormonal and gene expression alterations similar to those detected in light exposed wild-type seedlings. NO negatively impacted the transcript accumulation of genes encoding phytochromes, photomorphogenesis-repressor factors, and plastid division proteins, revealing that this free radical can mimic transcriptional changes typically triggered by phytochrome-dependent light perception. Therefore, our data indicate that negative and positive regulatory feedback loops orchestrate ethylene-NO and auxin-NO interactions, respectively, during the conversion of colorless etiolated seedlings into green, photosynthetically competent young plants. PMID- 26829982 TI - LLM-Domain Containing B-GATA Factors Control Different Aspects of Cytokinin Regulated Development in Arabidopsis thaliana. AB - Leu-Leu-Met (LLM)-domain B-GATAs are a subfamily of the 30-membered GATA transcription factor family from Arabidopsis. Only two of the six Arabidopsis LLM domain B-GATAs, i.e. GATA, NITRATE-INDUCIBLE, CARBON METABOLISM-INVOLVED (GNC) and its paralog GNC-LIKE/CYTOKININ-RESPONSIVE GATA FACTOR1 (GNL), have already been analyzed with regard to their biological function. Together, GNC and GNL control germination, greening, flowering time, and senescence downstream from auxin, cytokinin (CK), gibberellin (GA), and light signaling. Whereas overexpression and complementation analyses suggest a redundant biochemical function between GNC and GNL, nothing is known about the biological role of the four other LLM-domain B-GATAs, GATA15, GATA16, GATA17, and GATA17L (GATA17-LIKE), based on loss-of-function mutant phenotypes. Here, we examine insertion mutants of the six Arabidopsis B-GATA genes and reveal the role of these genes in the control of greening, hypocotyl elongation, phyllotaxy, floral organ initiation, accessory meristem formation, flowering time, and senescence. Several of these phenotypes had previously not been described for the gnc and gnl mutants or were enhanced in the more complex mutants when compared to gnc gnl mutants. Some of the respective responses may be mediated by CK signaling, which activates the expression of all six GATA genes. CK-induced gene expression is partially compromised in LLM-domain B-GATA mutants, suggesting that B-GATA genes play a role in CK responses. We furthermore provide evidence for a transcriptional cross regulation between these GATAs that may, in at least some cases, be at the basis of their apparent functional redundancy. PMID- 26829984 TI - Anti-C1q Autoantibodies from Systemic Lupus Erythematosus Patients Induce a Proinflammatory Phenotype in Macrophages. AB - Anti-C1q autoantibodies (anti-C1q) are frequently found in patients with systemic lupus erythematosus (SLE) and correlate with the occurrence of proliferative lupus nephritis. A previous study of anti-C1q in experimental lupus nephritis demonstrated an important role for FcgammaRs in the pathogenesis of lupus nephritis, suggesting a direct effect on phagocytes. Therefore, we developed an in vitro model to study the effect of SLE patient-derived anti-C1q bound to immobilized C1q (imC1q) on human monocyte-derived macrophages (HMDMs) obtained from healthy donors and SLE patients. HMDMs were investigated by analyzing the cell morphology, LPS-induced cytokine profile, surface marker expression, and phagocytosis rate of apoptotic Jurkat cells. Morphologically, bound anti-C1q induced cell aggregations of HMDMs compared with imC1q or IgG alone. In addition, anti-C1q reversed the effect of imC1q alone, shifting the LPS-induced cytokine release toward a proinflammatory response. FcgammaR-blocking experiments revealed that the secretion of proinflammatory cytokines was mediated via FcgammaRII. The anti-C1q-induced inflammatory cytokine profile was accompanied by a downregulation of CD163 and an upregulation of LPS-induced CD80, CD274, and MHC class II. Finally, HMDMs primed on bound anti-C1q versus imC1q alone displayed a significantly lower phagocytosis rate of early and late apoptotic cells accompanied by a reduced Mer tyrosine kinase expression. Interestingly, anti-C1q dependent secretion of proinflammatory cytokines was similar in SLE patient derived cells, with the exception that IL-10 was slightly increased. In conclusion, anti-C1q induced a proinflammatory phenotype in HMDMs reversing the effects of imC1q alone. This effect might exacerbate underlying pathogenic mechanisms in lupus nephritis. PMID- 26829983 TI - LLT1 and CD161 Expression in Human Germinal Centers Promotes B Cell Activation and CXCR4 Downregulation. AB - Germinal centers (GCs) are microanatomical structures critical for the development of high-affinity Abs and B cell memory. They are organized into two zones, light and dark, with coordinated roles, controlled by local signaling. The innate lectin-like transcript 1 (LLT1) is known to be expressed on B cells, but its functional role in the GC reaction has not been explored. In this study, we report high expression of LLT1 on GC-associated B cells, early plasmablasts, and GC-derived lymphomas. LLT1 expression was readily induced via BCR, CD40, and CpG stimulation on B cells. Unexpectedly, we found high expression of the LLT1 ligand, CD161, on follicular dendritic cells. Triggering of LLT1 supported B cell activation, CD83 upregulation, and CXCR4 downregulation. Overall, these data suggest that LLT1-CD161 interactions play a novel and important role in B cell maturation within the GC in humans. PMID- 26829985 TI - Dectin-1 Controls TLR9 Trafficking to Phagosomes Containing beta-1,3 Glucan. AB - Dectin-1 and TLR9 play distinct roles in the recognition and induction of innate immune responses to Aspergillus fumigatus and Candida albicans. Dectin-1 is a receptor for the major fungal cell wall carbohydrate beta-1,3 glucan that induces inflammatory cytokines and controls phagosomal maturation through spleen tyrosine kinase activation. TLR9 is an endosomal TLR that also modulates the inflammatory cytokine response to fungal pathogens. In this study, we demonstrate that beta 1,3 glucan beads are sufficient to induce dynamic redistribution and accumulation of cleaved TLR9 to phagosomes. Trafficking of TLR9 to A. fumigatus and C. albicans phagosomes requires Dectin-1 recognition. Inhibition of phagosomal acidification blocks TLR9 accumulation on phagosomes containing beta-1,3 glucan beads. Dectin-1-mediated spleen tyrosine kinase activation is required for TLR9 trafficking to beta-1,3 glucan-, A. fumigatus-, and C. albicans-containing phagosomes. In addition, Dectin-1 regulates TLR9-dependent gene expression. Collectively, our study demonstrates that recognition of beta-1,3 glucan by Dectin-1 triggers TLR9 trafficking to beta-1,3 glucan-containing phagosomes, which may be critical in coordinating innate antifungal defense. PMID- 26829987 TI - Intratumorally Establishing Type 2 Innate Lymphoid Cells Blocks Tumor Growth. AB - A long-standing question in the field of tumor immunotherapy is how Th2 cytokines block tumor growth. Their antitumor effects are particularly prominent when they are secreted continuously in tumors, suggesting that Th2 cytokines may create a tumor microenvironment unfavorable for tumor growth independently of adaptive immunity. In this study, we show that local production of IL-33 establishes a high number of type 2 innate lymphoid cells (ILC2s) with potent antitumor activity. IL-33 promotes secretion of a massive amount of CXCR2 ligands from ILC2s but creates a tumor microenvironment where tumor cells express CXCR2 through a dysfunctional angiogenesis/hypoxia/reactive oxygen species axis. These two signaling events converge to reinforce tumor cell-specific apoptosis through CXCR2. Our results identify a previously unrecognized antitumor therapeutic pathway wherein ILC2s play a central role. PMID- 26829986 TI - Calcitonin Gene-Related Peptide-Exposed Endothelial Cells Bias Antigen Presentation to CD4+ T Cells toward a Th17 Response. AB - Calcitonin gene-related peptide (CGRP) is a neuropeptide with well-established immunomodulatory functions. CGRP-containing nerves innervate dermal blood vessels and lymph nodes. We examined whether CGRP regulates the outcome of Ag presentation by Langerhans cells (LCs) to T cells through actions on microvascular endothelial cells (ECs). Exposure of primary murine dermal microvascular ECs (pDMECs) to CGRP followed by coculture with LCs, responsive CD4(+) T cells and Ag resulted in increased production of IL-6 and IL-17A accompanied by inhibition of IFN-gamma, IL-4, and IL-22 compared with wells containing pDMECs treated with medium alone. Physical contact between ECs and LCs or T cells was not required for this effect and, except for IL-4, we demonstrated that IL-6 production by CGRP-treated pDMECs was involved in these effects. CD4(+) cells expressing cytoplasmic IL-17A were increased, whereas cells expressing cytoplasmic IFN-gamma or IL-4 were decreased by the presence of CGRP-treated pDMECs. In addition, the level of retinoic acid receptor-related orphan receptor gammat mRNA was significantly increased, whereas T-bet and GATA3 expression was inhibited. Immunization at the site of intradermally administered CGRP led to a similar bias in CD4(+) T cells from draining lymph node cells toward IL-17A and away from IFN-gamma. Actions of nerve-derived CGRP on ECs may have important regulatory effects on the outcome of Ag presentation with consequences for the expression of inflammatory skin disorders involving Th17 cells. PMID- 26829990 TI - [Editorial]. PMID- 26829989 TI - Racial and ethnic disparities in use of 17-alpha hydroxyprogesterone caproate for prevention of preterm birth. AB - BACKGROUND: Racial/ethnic disparities in preterm birth remain a major public health challenge in the United States. While 17-alpha hydroxyprogesterone caproate (17OHP-C) is recommended for preterm birth prevention in women with a prior preterm birth, non-Hispanic black women continue to experience higher rates of recurrent preterm birth than white women receiving the same treatment. Further investigation of disparities in 17OHP-C use and adherence is warranted. OBJECTIVE: We sought to evaluate whether racial and ethnic disparities exist in the use of and adherence to 17OHP-C within a population of eligible women. STUDY DESIGN: This was a retrospective cohort study of women with a prior spontaneous, singleton preterm birth who were eligible for 17OHP-C for preterm birth prevention and received care at a single institution from 2010 through 2014. Associations between self-identified race/ethnicity (non-Hispanic black vs women in all other racial/ethnic groups) and documented counseling about 17OHP-C, receipt of any 17OHP-C, and adherence to 17OHP-C administration were each estimated by bivariable analysis and multivariable logistic regression. Adherence to 17OHP-C was defined as not >1 missed dose, initiation <20 weeks' gestational age, and continuation until 37 weeks or delivery. RESULTS: Of 472 women who were clinically eligible for 17OHP-C, 72% (N = 296) had documented 17OHP-C counseling and 48.9% (N = 229) received 17OHP-C. There were no differences in likelihood of 17OHP-C counseling or receipt of 17OHP-C based on race/ethnicity. While overall 83% (N = 176) of women were adherent to 17OHP-C, only 70% (N = 58) of non Hispanic black women were adherent, compared to 91% (N = 118) of all other women (P < .001). Non-Hispanic black women had more missed doses (2.4 vs 0.4 doses, P < .001) and later initiation of care (12.0 vs 10.2 weeks, P < .001) than women in other racial/ethnic groups. After adjustment for potential confounders, non Hispanic black women were significantly less likely to be adherent to 17OHP-C (adjusted odds ratio, 0.16; 95% confidence interval, 0.04-0.65). A significant interaction between non-Hispanic black race/ethnicity and public insurance was identified (adjusted odds ratio, 0.16; 95% confidence interval, 0.05-0.52). CONCLUSION: In a diverse cohort of women eligible for preterm birth prevention, non-Hispanic black women are at an increased risk of nonadherence to 17OHP-C. Non Hispanic black women with public insurance are at a particularly increased risk of nonadherence. PMID- 26829988 TI - PcpA Promotes Higher Levels of Infection and Modulates Recruitment of Myeloid Derived Suppressor Cells during Pneumococcal Pneumonia. AB - We used two different infection models to investigate the kinetics of the PcpA dependent pneumococcal disease in mice. In a bacteremic pneumonia model, we observed a PcpA-dependent increase in bacterial burden in the lungs, blood, liver, bronchoalveolar lavage, and spleens of mice at 24 h postinfection. This PcpA-dependent effect on bacterial burden appeared earlier (within 12 h) in the focal pneumonia model, which lacks bacteremia or sepsis. Histological changes show that the ability of pneumococci to make PcpA was associated with unresolved inflammation in both models of infection. Using our bacteremic pneumonia model we further investigated the effects of PcpA on recruitment of innate immune regulatory cells. The presence of PcpA was associated with increased IL-6 levels, suppressed production of TRAIL, and reduced infiltration of polymorphonuclear cells. The ability of pneumococci to make PcpA negatively modulated both the infiltration and apoptosis of macrophages and the recruitment of myeloid-derived suppressor-like cells. The latter have been shown to facilitate the clearance and control of bacterial pneumonia. Taken together, the ability to make PcpA was strongly associated with increased bacterial burden, inflammation, and negative regulation of innate immune cell recruitment to the lung tissue during bacteremic pneumonia. PMID- 26829991 TI - Incidence of West Nile virus infection in the Dallas-Fort Worth metropolitan area during the 2012 epidemic. AB - The 2012 West Nile virus (WNV) epidemic was the largest since 2003 and the North Texas region was the most heavily impacted. We conducted a serosurvey of blood donors from four counties in the Dallas-Fort Worth area to characterize the epidemic. Blood donor specimens collected in November 2012 were tested for WNV specific antibodies. Donors positive for WNV-specific IgG, IgM, and neutralizing antibodies were considered to have been infected in 2012. This number was adjusted using a multi-step process that accounted for timing of IgM seroreversion determined from previous longitudinal studies of WNV-infected donors. Of 4971 donations screened, 139 (2.8%) were confirmed WNV IgG positive, and 69 (1.4%) had IgM indicating infection in 2012. After adjusting for timing of sampling and potential seroreversion, we estimated that 1.8% [95% confidence interval (CI) 1.5-2.2] of the adult population in the Dallas-Fort Worth area were infected during 2012. The resulting overall estimate for the ratio of infections to reported WNV neuroinvasive disease (WNND) cases was 238:1 (95% CI 192-290), with significantly increased risk of WNND in older age groups. These findings were very similar to previous estimates of infections per WNND case, indicating no change in virulence as WNV evolved into an endemic infection in the United States. PMID- 26829992 TI - Cutaneous Collagenous Vasculopathy: A Case Report and Review of the Literature. PMID- 26829993 TI - Evaluation of Collision Tumors by Confocal Microscopy. PMID- 26829994 TI - A Familial Form of Primary Essential Cutis Verticis Gyrata. PMID- 26829995 TI - Distribution of virulence associated traits among urine Escherichia coli isolates from patients in onco-hematology. AB - Escherchia coli is the most common etiological agent of urinary tract infections. In this study we had two goals: First of all, to find out if urine stains isolated from our patients--having the particularity of being immunocompromised- would have a virulence genes distribution different from the one observed in strains isolated from ordinary patients. Second, we wanted to identify a common virulence profile associated to these particular strains. The prevalence of virulence factors (VF)-encoding genes was analyzed by PCR. Of the tested VF encoding genes, malX (80%), ompT (79%), fyuA (74%), usp (67%), chuA (66%), iroN (59%), iutA (56%), papC (36%), pap AH (30%), papEF (28%), hlyA (28%), papG allele II (25%), cnf1 (21%), focG (20%),cvaC (20%) and papG allele III (7%) were significantly associated to urinary strains. Virulence genes distribution of urinary strains isolated from onco-hematology patients and the one observed in strains isolated from ordinary patients are almost the same. The virulence profiles containing adhesins type 1, S and F1C fimbriae, siderophore genes and three individual genes ompT, usp and malX were present in half of the urinary strains and were significantly associated to them. Two virulence signatures occurred significantly in UTI-causing strains (12%). These findings provide first insight into the virulence of UTI-causing E. coli strains isolated in onco hematology patients. PMID- 26829996 TI - Bacteremia secondary to Alloscardovia omnicolens urinary tract infection. AB - A 70-year-old woman was admitted to our hospital with malaise, bilateral leg edema, and oliguria. She had a history of advanced uterine cancer. Bilateral double-J catheters were inserted because growth of intra-abdominal metastases led to bilateral ureteral stricture and hydronephrosis. Two days later, she suddenly developed high fever. Thin gram-positive bacilli of moderate length were detected in the anaerobic blood culture bottles. We performed 16S ribosomal RNA analysis of the isolate and it showed 100% match with Alloscardovia omnicolens DSM 21503(T). She was successfully treated with cefmetazole in addition to percutaneous nephrostomy. PMID- 26829997 TI - Chondrogenic differentiation of human mesenchymal stem cells on fish scale collagen. AB - Fish collagen has recently been reported to be a novel biomaterial for cell and tissue culture as an alternative to conventional mammalian collagens such as bovine and porcine collagens. Fish collagen could overcome the risk of zoonosis, such as from bovine spongiform encephalopathy. Among fish collagens, tilapia collagen, the denaturing temperature of which is near 37 degrees C, is appropriate for cell and tissue culture. In this study, we investigated chondrogenic differentiation of human mesenchymal stem cells (hMSCs) cultured on tilapia scale collagen fibrils compared with porcine collagen and non-coated dishes. The collagen fibrils were observed using a scanning electronic microscope. Safranin O staining, glycosaminoglycans (GAG) expression, and real time PCR were examined to evaluate chondrogenesis of hMSCs on each type of collagen fibril. The results showed that hMSCs cultured on tilapia scale collagen showed stronger Safranin O staining and higher GAG expression at day 6. Results of real-time PCR indicated that hMSCs cultured on tilapia collagen showed earlier SOX9 expression on day 4 and higher AGGRECAN and COLLAGEN II expression on day 6 compared with on porcine collagen and non-coated dishes. Furthermore, low mRNA levels of bone gamma-carboxyglutamate, a specific marker of osteogenesis, showed that tilapia collagen fibrils specifically enhanced chondrogenic differentiation of hMSCs in chondrogenic medium, as well as porcine collagen. Accordingly, tilapia scale collagen may provide an appropriate collagen source for hMSC chondrogenesis in vitro. PMID- 26829998 TI - Mental health and psychosocial wellbeing of Syrians affected by armed conflict. AB - AIMS: This paper is based on a report commissioned by the United Nations High Commissioner for Refugees, which aims to provide information on cultural aspects of mental health and psychosocial wellbeing relevant to care and support for Syrians affected by the crisis. This paper aims to inform mental health and psychosocial support (MHPSS) staff of the mental health and psychosocial wellbeing issues facing Syrians who are internally displaced and Syrian refugees. METHODS: We conducted a systematic literature search designed to capture clinical, social science and general literature examining the mental health of the Syrian population. The main medical, psychological and social sciences databases (e.g. Medline, PubMed, PsycInfo) were searched (until July 2015) in Arabic, English and French language sources. This search was supplemented with web-based searches in Arabic, English and French media, and in assessment reports and evaluations, by nongovernmental organisations, intergovernmental organisations and agencies of the United Nations. This search strategy should not be taken as a comprehensive review of all issues related to MHPSS of Syrians as some unpublished reports and evaluations were not reviewed. RESULTS: Conflict affected Syrians may experience a wide range of mental health problems including (1) exacerbations of pre-existing mental disorders; (2) new problems caused by conflict related violence, displacement and multiple losses; as well as (3) issues related to adaptation to the post-emergency context, for example living conditions in the countries of refuge. Some populations are particularly vulnerable such as men and women survivors of sexual or gender based violence, children who have experienced violence and exploitation and Syrians who are lesbian, gay, bisexual, transgender or intersex. Several factors influence access to MHPSS services including language barriers, stigma associated with seeking mental health care and the power dynamics of the helping relationship. Trust and collaboration can be maximised by ensuring a culturally safe environment, respectful of diversity and based on mutual respect, in which the perspectives of clients and their families can be carefully explored. CONCLUSIONS: Sociocultural knowledge and cultural competency can improve the design and delivery of interventions to promote mental health and psychosocial wellbeing of Syrians affected by armed conflict and displacement, both within Syria and in countries hosting refugees from Syria. PMID- 26830000 TI - The range and nature of effective interactions in hard-sphere solids. AB - Colloidal systems observed in video microscopy are often analysed using the displacements correlation matrix of particle positions. In non-thermal systems, the inverse of this matrix can be interpreted as a pair-interaction potential between particles. If the system is thermally agitated, however, only an effective interaction is accessible from the correlation matrix. We show how this effective interaction differs from the non-thermal case by comparing with high statistics numerical data from hard-sphere crystals. PMID- 26829999 TI - The GyrA encoded gene: A pertinent marker for the phylogenetic revision of Helicobacter genus. AB - Phylogeny of Epsilonproteobacteria is based on sequencing of the 16S rRNA gene. However, this gene is not sufficiently discriminatory in Helicobacter species and alternative markers would be useful. In this study, the 16S rRNA, gyrA, hsp60, gyrB, and ureA-ureB gene sequences, as well as GyrA, HSP60 and GyrB protein sequences were analyzed as tools to support Helicobacter species phylogeny: 72 Helicobacter strains, belonging to 41 species of which 36 are validated species, were included. Results of the phylogenetic reconstructions of the GyrA gene encoded protein (approximately 730 residues) indicated the most stable trees to bootstrap resampling with a good separation of Helicobacter taxa, especially between gastric and enterohepatic species. Moreover, the GyrA tree revealed high similarity with that of the gyrB and ureA-ureB genes (restricted to urease positive Helicobacter species). However, some differences in clustering were observed when compared to the hsp60 and 23S rRNA gene trees. Altogether, these revised phylogenies (except the 16S rRNA gene for enterohepatic Helicobacters) enabled reliable clustering of Helicobacter cinaedi and 'Flexispira' strains, determined a reliable position for Helicobacter mustelae (except the hsp60 gene) and for novel Helicobacter species proposed such as 'Helicobacter sanguini', 'Helicobacter apodemus' or 'Helicobacter winghamensis', and suggest that Helicobacter species MIT 09-6949 and MIT 05-5293 isolated from rodents constitute novel species. Although they are not commonly used to study the phylogeny of Epsilonproteobacteria, protein sequences and, in particular, the GyrA protein sequence may constitute pertinent phylogenetic markers for Helicobacter genus. PMID- 26830001 TI - Are the Oxford((r)) medial unicompartmental knee arthroplasty new instruments reducing the bearing dislocation risk while improving components relationships? A case control study. AB - INTRODUCTION: The recently introduced Microplasty((r)) system is an upgrade of conventional phase III instrumentation. However, little is known of its impact on the position of the implant following the Oxford((r)) mobile-bearing unicompartmental knee arthroplasty (UKA). This study investigated whether the Microplasty((r)) instrumentation system can improve the positioning of the implant and reduce the rate of early failure. HYPOTHESIS: Microplasty((r)) provides a better positioning and decreases the rate of dislocation. MATERIALS AND METHODS: The medical records and radiographs of 82 consecutive Oxford((r)) UKAs were reviewed retrospectively. The radiographic parameters and prevalence of early failure of 41 UKAs performed with the Microplasty((r)) system and 41 UKAs using the conventional instrumentation system were compared. Both groups were comparable in terms of demographics and preoperative status. RESULTS: The femoral components in the Microplasty((r)) group were more contiguously placed and more convergent in relation to the tibial components compared to the conventional instrumentation system (P<0.01). The frequency of bearing dislocation was lower in the Microplasty((r)) group (P=0.04). A wide gap and the angle between components were associated with an increased risk of bearing dislocation. CONCLUSION: The Microplasty((r)) instrumentation system consistently placed the femoral and tibial components in more contiguous and convergent positions. Such changes in position decreased the risk of bearing dislocations by reducing the space available for bearing rotation. LEVEL OF EVIDENCE: Level III, case control study. PMID- 26830002 TI - MTPA control of mechanical sensorless IPMSM based on adaptive nonlinear control. AB - In this paper, an adaptive nonlinear control scheme has been proposed for implementing maximum torque per ampere (MTPA) control strategy corresponding to interior permanent magnet synchronous motor (IPMSM) drive. This control scheme is developed in the rotor d-q axis reference frame using adaptive input-output state feedback linearization (AIOFL) method. The drive system control stability is supported by Lyapunov theory. The motor inductances are online estimated by an estimation law obtained by AIOFL. The estimation errors of these parameters are proved to be asymptotically converged to zero. Based on minimizing the motor current amplitude, the MTPA control strategy is performed by using the nonlinear optimization technique while considering the online reference torque. The motor reference torque is generated by a conventional rotor speed PI controller. By performing MTPA control strategy, the generated online motor d-q reference currents were used in AIOFL controller to obtain the SV-PWM reference voltages and the online estimation of the motor d-q inductances. In addition, the stator resistance is online estimated using a conventional PI controller. Moreover, the rotor position is detected using the online estimation of the stator flux and online estimation of the motor q-axis inductance. Simulation and experimental results obtained prove the effectiveness and the capability of the proposed control method. PMID- 26830003 TI - Learning from adaptive neural network output feedback control of a unicycle-type mobile robot. AB - This paper studies learning from adaptive neural network (NN) output feedback control of nonholonomic unicycle-type mobile robots. The major difficulties are caused by the unknown robot system dynamics and the unmeasurable states. To overcome these difficulties, a new adaptive control scheme is proposed including designing a new adaptive NN output feedback controller and two high-gain observers. It is shown that the stability of the closed-loop robot system and the convergence of tracking errors are guaranteed. The unknown robot system dynamics can be approximated by radial basis function NNs. When repeating same or similar control tasks, the learned knowledge can be recalled and reused to achieve guaranteed stability and better control performance, thereby avoiding the tremendous repeated training process of NNs. PMID- 26830004 TI - Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum. AB - DNA methylation (DNAm) levels lend themselves for defining an epigenetic biomarker of aging known as the 'epigenetic clock'. Our genome-wide association study (GWAS) of cerebellar epigenetic age acceleration identifies five significant (P<5.0 * 10(-8)) SNPs in two loci: 2p22.1 (inside gene DHX57) and 16p13.3 near gene MLST8 (a subunit of mTOR complex 1 and 2). We find that the SNP in 16p13.3 has a cis-acting effect on the expression levels of MLST8 (P=6.9 * 10( 18)) in most brain regions. In cerebellar samples, the SNP in 2p22.1 has a cis effect on DHX57 (P=4.4 * 10(-5)). Gene sets found by our GWAS analysis of cerebellar age acceleration exhibit significant overlap with those of Alzheimer's disease (P=4.4 * 10(-15)), age-related macular degeneration (P=6.4 * 10(-6)), and Parkinson's disease (P=2.6 * 10(-4)). Overall, our results demonstrate the utility of a new paradigm for understanding aging and age-related diseases: it will be fruitful to use epigenetic tissue age as endophenotype in GWAS. PMID- 26830005 TI - Phylogenomic and biogeographic reconstruction of the Trichinella complex. AB - Trichinellosis is a globally important food-borne parasitic disease of humans caused by roundworms of the Trichinella complex. Extensive biological diversity is reflected in substantial ecological and genetic variability within and among Trichinella taxa, and major controversy surrounds the systematics of this complex. Here we report the sequencing and assembly of 16 draft genomes representing all 12 recognized Trichinella species and genotypes, define protein coding gene sets and assess genetic differences among these taxa. Using thousands of shared single-copy orthologous gene sequences, we fully reconstruct, for the first time, a phylogeny and biogeography for the Trichinella complex, and show that encapsulated and non-encapsulated Trichinella taxa diverged from their most recent common ancestor ~21 million years ago (mya), with taxon diversifications commencing ~10-7 mya. PMID- 26830007 TI - Targeting autophagy as a potential therapeutic approach for immune thrombocytopenia therapy. AB - Autophagy involves the sequestration and lysosomal degradation of various cytoplasmic structures, including damaged organelles and invading microorganisms. Autophagy is not only an essential cell-intrinsic mechanism for protecting against internal and external stress conditions but is also key in the cellular response against microbes, in antigen processing for major histocompatibility complex (MHC) presentation, and in lymphocyte development, survival, and proliferation. In recent years, perturbations in autophagy have been implicated in a number of diseases, including autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). Immune thrombocytopenia (ITP) is a multifactorial disease characterized by autoimmune responses to self-platelet membrane proteins. Recently, our unpublished original data demonstrated aberrant expression of molecules in the autophagy pathway in ITP patients compared with controls, and we found a close correlation between the pathogenesis of ITP and the autophagy pathway. The potential of targeting the autophagy pathway in ITP as a novel therapeutic approach has been discussed. PMID- 26830006 TI - Implication of retinoic acid receptor selective signaling in myogenic differentiation. AB - Signaling molecules are important for committing individual cells into tissue specific lineages during early vertebrate development. Retinoic acid (RA) is an important vertebrate morphogen, in that its concentration gradient is essential for correct patterning of the vertebrate embryo. RA signaling is mediated through the activation of retinoic acid receptors (RARs), which function as ligand dependent transcription factors. In this study, we examined the molecular mechanisms of RAR-selective signaling in myogenic differentiation. We found that just like natural ligand RA, a RAR-selective ligand is an effective enhancer in the commitment of skeletal muscle lineage at the early stage of myogenic differentiation. Interestingly, the kinetics and molecular basis of the RAR selective ligand in myogenic differentiation are similar to that of natural ligand RA. Also similar to natural ligand RA, the RAR-selective ligand enhances myogenic differentiation through beta-catenin signaling pathway while inhibiting cardiac differentiation. Furthermore, while low concentrations of natural ligand RA or RAR-selective ligand regulate myogenic differentiation through RAR function and coactivator recruitment, high concentrations are critical to the expression of a model RA-responsive gene. Thus our data suggests that RAR-mediated gene regulation may be highly context-dependent, affected by locus-specific interaction or local chromatin environment. PMID- 26830008 TI - Do the smoking intensity and duration, the years since quitting, the methodological quality and the year of publication of the studies affect the results of the meta-analysis on cigarette smoking and Acute Myeloid Leukemia (AML) in adults? AB - BACKGROUND: The aim was to perform a systematic review and meta-analysis on the relationship between tobacco smoking and the onset of acute myeloid leukemia (AML) in adults. METHODS: PubMed and Scopus databases were systematically searched. In the meta-analysis, random or fixed effects models were used according to the presence of heterogeneity. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Twenty-seven articles were included. Case control and cohort meta-analyses show that current, ever and former smokers have a significant increased risk to develop AML compared to never smokers [current: OR=1.36 (1.11-1.66) and RR=1.52 (1.10-2.14); ever: OR=1.25 (1.14-1.38) and RR=1.45 (1.10-1.90); former: OR=1.21 (1.03-1.41) and RR=1.45 (1.08-1.94)]. Moreover, increasing smoking intensity and duration is associated with an increase of the risk, OR shift from 1.14 (1-20 pack/years) to 2.36 (>40 pack/years). DISCUSSION AND CONCLUSION: Smoking may have a significant role in AML onset in a multistep pathogenesis. PMID- 26830009 TI - Therapeutic options in recurrent glioblastoma--An update. AB - INTRODUCTION: Standards of care are not yet defined in recurrent glioblastoma. METHODS: We reviewed the literature on clinical trials for recurrent glioblastoma available in PubMed and American Society of Clinical Oncology (ASCO) abstracts until June 2015. RESULTS: Evidence is limited due to the paucity of randomized controlled studies. Second surgery or re-irradiation are options for selected patients. Alkylating chemotherapy such as nitrosoureas or temozolomide and the vascular endothelial growth factor (VEGF) antibody, bevacizumab, exhibit comparable single agent activity. Phase III data exploring the benefit of combining bevacizumab and lomustine are emerging. Novel approaches in the fields of targeted therapy, immunotherapy, and tumor metabolism are coming forward. Several biomarkers are being explored, but, except for O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation, none has assumed a role in clinical practice. CONCLUSION: Proper patient selection, development of predictive biomarkers and randomized controlled studies are required to develop evidence-based concepts for recurrent glioblastoma. PMID- 26830010 TI - Evaluation of the relationship between major dietary patterns and uninvestigated reflux among Iranian adults. AB - OBJECTIVES: The etiology of uninvestigated reflux is largely unknown. Although diet has been associated with uninvestigated reflux, the role of dietary patterns is not clear yet. The aim of this study was to investigate dietary patterns in relation to uninvestigated reflux among Iranian adults. METHODS: This cross sectional study was carried out within the framework of SEPAHAN (Study on the Epidemiology of Psychological, Alimentary Health and Nutrition) among Iranian adults. Dietary data were collected using a self-administered, 106-item, dish based, semiquantitative food frequency questionnaire. Uninvestigated reflux was considered to be present when an individual reported to be suffering from heartburn sometimes or frequently in the preceding 3 mo. Specific dietary patterns were identified using factor analysis. RESULTS: Complete information from 3846 individuals was available for statistical analysis. We identified four major dietary patterns: fast food, traditional, vegetarian, and Western. After controlling for potential confounders, no overall significant associations were found between these dietary patterns and uninvestigated reflux. However, participants in the third quintile of the traditional dietary pattern had greater odds of uninvestigated reflux, either in the crude (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.09-1.74) or the adjusted (OR, 1.52; 95% CI, 1.16 2.00) model taking into account different confounders. After controlling for age, men in the second (OR, 1.64; 95% CI, 1.10-2.45) and women in the fourth (OR, 1.47; 95% CI, 1.02-2.11) quintiles of the fast food dietary pattern were more likely to have uninvestigated reflux. Moreover, in the age-adjusted model, men in the second (OR, 1.72; 95% CI, 1.14-2.59) and fourth (OR, 1.56; 95% CI, 1.03-2.35) quintiles, and women in the second (OR, 1.48; 95% CI, 1.08-2.04) quintile of the traditional dietary pattern were at higher risk for being diagnosed with uninvestigated reflux. CONCLUSION: Although the present study showed no statistically significant associations between major dietary patterns and the risk for uninvestigated reflux, relative positive associations were found between uninvestigated reflux and adherence to either fast food or traditional dietary patterns, suggesting that these contribute to the risk for developing reflux. PMID- 26830011 TI - Dietary flavonoid intake, total antioxidant capacity and lipid oxidative damage: A cross-sectional study of Iranian women. AB - OBJECTIVES: Although strong evidence supports the antioxidant potential of flavonoids in vitro, the effect of flavonoids at physiological concentrations on the overall antioxidant status in humans is inconsistent. The aim of this study was to examine cross-sectional associations between total flavonoid consumption, serum total antioxidant capacity (TAC), and malondialdehyde (MDA) levels in apparently healthy women. METHODS: Through a multistage cluster sampling, 170 women ages 20 to 48 y were recruited. The usual dietary flavonoid intake was estimated using a semiquantitive food frequency questionnaire (FFQ) by matching food items with the US Department of Agriculture flavonoid databases. General linear models were used to compare the biochemical parameters across tertiles of flavonoid intakes. RESULTS: As dietary anthocyanin intake rose from the lowest to the highest tertile, the multivariate-adjusted mean TAC concentrations significantly increased from 1.08 to 1.28 (Ptrend = 0.01). This association was still significant after adjustment for fruit and vegetable intake and antioxidant vitamins (Ptrend = 0.03). The highest tertile of total flavonoid intake and theaflavins had higher mean concentrations of TAC than did the lowest tertile, but there was no linear trend (P < 0.05). There were statistically significant positive relationships between dietary intake of grapes and eggplant as main food sources of anthocyanins and serum TAC (P = 0.02 and 0.04, respectively). No significant associations were found between MDA and flavonoids intakes (P > 0.05). CONCLUSIONS: The findings of the present study support the attribution of anthocyanins to overall antioxidant status. However, further research is needed to confirm these observed associations. PMID- 26830012 TI - A novel combined glucocorticoid-mineralocorticoid receptor selective modulator markedly prevents weight gain and fat mass expansion in mice fed a high-fat diet. AB - BACKGROUND: We have previously shown that antagonism of the mineralocorticoid receptor (MR) results in a potent antiadipogenic activity, in vitro and in vivo. Excessive glucocorticoid exposure is associated with obesity and related disorders in humans and mice. METHODS: In this study, responses to a novel combined glucocorticoid receptor (GR)/MR antagonist were investigated in a model of diet-induced obesity. Female 10-week-old C57BL/6J mice were fed with normal chow or a high-fat diet (HFD) for 9 weeks. Mice fed a HFD were concomitantly treated for 9 weeks with the GR antagonist mifepristone (80 mg kg(-1) per day) or the novel combined GR/MR antagonist CORT118335 (80 mg kg(-1) per day). Male, juvenile 6-week-old C57BL/6J mice fed HFD were treated with CORT118335 for 4 weeks. RESULTS: Mice fed a HFD showed a significant increase in total body weight and white fat mass, with impaired glucose tolerance and increased fat infiltration in livers. Interestingly, only CORT118335 completely prevented the HFD-induced weight gain and white fat deposition, whereas mifepristone showed no effect on body weight and modestly increased subcutaneous fat mass. Importantly, food intake was not affected by either treatment, and CORT118335 dramatically increased PGC-1alpha protein expression in adipose tissue, without any effect on UCP1. Both CORT118335 and mifepristone produced metabolic benefit, improving glucose tolerance, increasing adiponectin plasma levels, decreasing leptin and reducing mean adipocyte size. When tested in vitro, CORT118335 markedly reduced 3T3-L1 differentiation and reversed MR-mediated pro-adipogenic effects of aldosterone; differently, GR-mediated effects of dexamethasone were not antagonized by CORT118335, suggesting that it mostly acts as an antagonist of MR in cultured preadipocytes. CONCLUSIONS: Combined GR/MR pharmacological antagonism markedly reduced HFD-driven weight gain and fat mass expansion in mice through the increase in adipose PGC-1alpha, suggesting that both receptors represent strategic therapeutic targets to fight obesity. The effects of CORT118335 in adipocytes seem predominantly mediated by MR antagonism. PMID- 26830013 TI - Crosstalk between miRNAs and their regulated genes network in stroke. AB - In recent years, more and more studies focus on the roles of genes or miRNAs in stroke. However, the molecular mechanism connecting miRNAs and their targetgenes remains unclear. The aim of this study was to determine the differential regulation and correlations between miRNAs and their targetgenes in human stroke. Stroke-related miRNAs were obtained from the Human MicroRNA Disease Database (HMDD) and their targetgenes were generated from three independent sources. Kappa score was used to create the network and the functional modules. A total of 11 stroke-related miRNAs were identified from the HMDD and 441 overlapping targetgenes were extracted from the three databases. By network construction and GO analysis, 13 functional modules, 186 biological processes, and 21 pathways were found in the network, of which functional module 8 was the largest module, cellular-related process and phosphate-related process were the most important biological processes, and MAPK signaling pathway was the most significant pathway. In our study, all miRNAs regulate the stroke modular network by their targetgenes. After the validation of miRNAs, we found that miR-605 and miR-181d were highly expressed in the blood of stroke patients which never reported before may supply novel target for treatment. PMID- 26830014 TI - Installing amino acids and peptides on N-heterocycles under visible-light assistance. AB - Readily available natural alpha-amino acids are one of nature's most attractive and versatile building blocks in synthesis of natural products and biomolecules. Peptides and N-heterocycles exhibit various biological and pharmaceutical functions. Conjugation of amino acids or peptides with N-heterocycles provides boundless potentiality for screening and discovery of diverse biologically active molecules. However, it is a great challenge to install amino acids or peptides on N-heterocycles through formation of carbon-carbon bonds under mild conditions. In this article, eighteen N-protected alpha-amino acids and three peptides were well assembled on phenanthridine derivatives via couplings of N-protected alpha-amino acid and peptide active esters with substituted 2-isocyanobiphenyls at room temperature under visible-light assistance. Furthermore, N-Boc-proline residue was successfully conjugated with oxindole derivatives using similar procedures. The simple protocol, mild reaction conditions, fast reaction, and high efficiency of this method make it an important strategy for synthesis of diverse molecules containing amino acid and peptide fragments. PMID- 26830015 TI - Changes in intestinal microflora of Caenorhabditis elegans following Bacillus nematocida B16 infection. AB - The effect of pathogenic bacteria on a host and its symbiotic microbiota is vital and widespread in the biotic world. The soil-dwelling opportunistic bacterium Bacillus nematocida B16 uses a "Trojan horse" mechanism to kill Caenorhabditis elegans. The alterations in the intestinal microflora that occur after B16 infection remain unknown. Here, we analyzed the intestinal bacteria presented in normal and infected worms. The gut microbial community experienced a complex change after B16 inoculation, as determined through marked differences in species diversity, structure, distribution and composition between uninfected and infected worms. Regardless of the worm's origin (i.e., from soil or rotten fruits), the diversity of the intestinal microbiome decreased after infection. Firmicutes increased sharply, whereas Proteobacteria, Actinobacteria, Cyanobacteria and Acidobacteria decreased to different degrees. Fusobacteria was only present 12 h post-infection. After 24 h of infection, 1228 and 1109 bacterial species were identified in the uninfected and infected groups, respectively. The shared species reached 21.97%. The infected group had a greater number of Bacillus species but a smaller number of Pediococcus, Halomonas, Escherichia and Shewanella species (P < 0.01). Therefore, this study provides the first evaluation of the alterations caused by pathogenic bacteria on symbiotic microbiota using C. elegans as the model species. PMID- 26830016 TI - Plutonium, 137Cs and uranium isotopes in Mongolian surface soils. AB - Plutonium (238Pu and 239,240Pu), 137Cs and plutonium activity ratios (238Pu/239,240Pu) as did uranium isotope ratio (235U/238U) were measured in surface soil samples collected in southeast Mongolia. The 239,240Pu and 137Cs concentrations in Mongolian surface soils (<53 MUm of particle size) ranged from 0.42 +/- 0.03 to 3.53 +/- 0.09 mBq g-1 and from 11.6 +/- 0.7 to 102 +/- 1 mBq g 1, respectively. The 238Pu/239,240Pu activity ratios in the surface soils (0.013 0.06) coincided with that of global fallout. The 235U/238U atom ratios in the surface soil show the natural one. There was a good correlation between the 239,240Pu and 137Cs concentrations in the surface soils. We introduce the migration depth to have better understanding of migration behaviors of anthropogenic radionuclides in surface soil. We found a difference of the migration behavior between 239,240Pu and 137Cs from 137Cs/239,240Pu - 137Cs plots for the Mongolian and Tsukuba surface soils; plutonium in surface soil is migrated easier than 137Cs. PMID- 26830018 TI - Absolute 3D reconstruction of thin films topography in microfluidic channels by interference reflection microscopy. AB - The travel of droplets, bubbles, vesicles, capsules, living cells or small organisms in microchannels is a hallmark in microfluidics applications. A full description of the dynamics of such objects requires a quantitative understanding of the complex hydrodynamic and interfacial interactions between objects and channel walls. In this paper, we present an interferometric method that allows absolute topographic reconstruction of the interspace between an object and channel walls for objects confined in microfluidic channels. Wide field microscopic imaging in reflection interference contrast mode (RICM) is directly performed at the bottom wall of microfluidic chips. Importantly, we show that the reflections at both the lower and upper surface of the microchannel have to be considered in the quantitative analysis of the optical signal. More precisely, the contribution of the reflection at the upper surface is weighted depending on the light coherence length and channel height. Using several wavelengths and illumination apertures, our method allows reconstructing the topography of thin films on channel walls in a range of 0-500 nm, with a precision as accurate as 2 nm for the thinnest films. A complete description of the protocol is exemplified for oil in water droplets travelling in channels of height 10-400 MUm at a speed up to 5 mm s(-1). PMID- 26830017 TI - Subgroup J avian leukosis virus infection of chicken dendritic cells induces apoptosis via the aberrant expression of microRNAs. AB - Subgroup J avian leukosis virus (ALV-J) is an oncogenic retrovirus that causes immunosuppression and enhances susceptibility to secondary infection. The innate immune system is the first line of defense in preventing bacterial and viral infections, and dendritic cells (DCs) play important roles in innate immunity. Because bone marrow is an organ that is susceptible to ALV-J, the virus may influence the generation of bone marrow-derived DCs. In this study, DCs cultured in vitro were used to investigate the effects of ALV infection. The results revealed that ALV-J could infect these cells during the early stages of differentiation, and infection of DCs with ALV-J resulted in apoptosis. miRNA sequencing data of uninfected and infected DCs revealed 122 differentially expressed miRNAs, with 115 demonstrating upregulation after ALV-J infection and the other 7 showing significant downregulation. The miRNAs that exhibited the highest levels of upregulation may suppress nutrient processing and metabolic function. These results indicated that ALV-J infection of chicken DCs could induce apoptosis via aberrant microRNA expression. These results provide a solid foundation for the further study of epigenetic influences on ALV-J-induced immunosuppression. PMID- 26830019 TI - The phylogeny and evolutionary history of tyrannosauroid dinosaurs. AB - Tyrannosauroids--the group of carnivores including Tyrannosaurs rex--are some of the most familiar dinosaurs of all. A surge of recent discoveries has helped clarify some aspects of their evolution, but competing phylogenetic hypotheses raise questions about their relationships, biogeography, and fossil record quality. We present a new phylogenetic dataset, which merges published datasets and incorporates recently discovered taxa. We analyze it with parsimony and, for the first time for a tyrannosauroid dataset, Bayesian techniques. The parsimony and Bayesian results are highly congruent, and provide a framework for interpreting the biogeography and evolutionary history of tyrannosauroids. Our phylogenies illustrate that the body plan of the colossal species evolved piecemeal, imply no clear division between northern and southern species in western North America as had been argued, and suggest that T. rex may have been an Asian migrant to North America. Over-reliance on cranial shape characters may explain why published parsimony studies have diverged and filling three major gaps in the fossil record holds the most promise for future work. PMID- 26830020 TI - Vagus Nerve Stimulation Improves Cardiac Function by Preventing Mitochondrial Dysfunction in Obese-Insulin Resistant Rats. AB - Long-term high-fat diet (HFD) consumption leads to not only obese-insulin resistance, but also impaired left ventricular (LV) function. Vagus nerve stimulation (VNS) has been shown to exert cardioprotection. However, its effects on the heart and metabolic parameters under obese-insulin resistant condition is not known. We determined the effects of VNS on metabolic parameters, heart rate variability (HRV) and LV function in obese-insulin resistant rats. Male Wistar rats were fed with HFD for 12 weeks, and were randomly divided into sham and VNS groups. VNS was applied for the next 12 weeks. Echocardiography, blood pressure and HRV were examined. Blood samples were collected for metabolic parameters. At the end, the heart was removed for determination of apoptosis, inflammation, oxidative stress, and cardiac mitochondrial function. VNS for 12 weeks significantly decreased plasma insulin, HOMA index, total cholesterol, triglyceride, LDL and visceral fat. Serum adiponectin was significantly increased in the VNS group. VNS also significantly decreased blood pressure, improved HRV and LV function, decreased cardiac MDA, TNF-alpha and Bax levels, and improved cardiac mitochondrial function. VNS improves metabolic and hemodynamic parameters, and the LV function via its ability against apoptosis, inflammation and oxidative stress, and preserved cardiac mitochondrial function in obese insulin resistant rats. PMID- 26830022 TI - Upper airway obstruction due to a change in altitude: first report in fifty years. AB - BACKGROUND: Air travel mostly causes minor ear, nose and throat complaints. We describe a second report in literature of airway obstruction caused by a drop in atmospheric pressure during a routine commercial flight. CASE PRESENTATION: A 54 year-old male was referred to a head and neck surgeon with a 2 cm left submandibular mass that would enlarge during commercial flights. As the plane gained elevation, the mass would grow and cause him to become stridorous and short of breath. The shortness of breath and stridor would only resolve upon landing of the plane. A CT scan showed a large air sac extending from the larynx at the level of the true vocal cords up to the angle of the mandible. Based on the history and the CT findings a diagnosis of a laryngocele was made. The laryngocele was excised using an external approach, resolving the patient's difficulty with flying. CONCLUSION: This article reports a rare case of upper airway obstruction caused by atmospheric pressure changes during air travel. The reported case is of significance as only a few uncomplicated laryngoceles have been reported to cause airway distress in the literature. This report highlights the epidemiology, presentation, complication and management of laryngoceles. PMID- 26830021 TI - Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1. AB - Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features multiple autoimmune disease manifestations. It is caused by mutations in the Autoimmune regulator (AIRE) gene, which promote thymic display of thousands of peripheral tissue antigens in a process critical for establishing central immune tolerance. We here used proteome arrays to perform a comprehensive study of autoimmune targets in APS1. Interrogation of established autoantigens revealed highly reliable detection of autoantibodies, and by exploring the full panel of more than 9000 proteins we further identified MAGEB2 and PDILT as novel major autoantigens in APS1. Our proteome-wide assessment revealed a marked enrichment for tissue-specific immune targets, mirroring AIRE's selectiveness for this category of genes. Our findings also suggest that only a very limited portion of the proteome becomes targeted by the immune system in APS1, which contrasts the broad defect of thymic presentation associated with AIRE-deficiency and raises novel questions what other factors are needed for break of tolerance. PMID- 26830023 TI - Metabolic engineering of Saccharomyces cerevisiae to produce 1-hexadecanol from xylose. AB - BACKGROUND: An advantageous but challenging approach to overcome the limited supply of petroleum and relieve the greenhouse effect is to produce bulk chemicals from renewable materials. Fatty alcohols, with a billion-dollar global market, are important raw chemicals for detergents, emulsifiers, lubricants, and cosmetics production. Microbial production of fatty alcohols has been successfully achieved in several industrial microorganisms. However, most of the achievements were using glucose, an edible sugar, as the carbon source. To produce fatty alcohols in a renewable manner, non-edible sugars such as xylose will be a more appropriate feedstock. RESULTS: In this study, we aim to engineer a Saccharomyces cerevisiae strain that can efficiently convert xylose to fatty alcohols. To this end, we first introduced the fungal xylose utilization pathway consisting of xylose reductase (XR), xylitol dehydrogenase (XDH), and xylulose kinase (XKS) into a fatty alcohol-producing S. cerevisiae strain (XF3) that was developed in our previous studies to achieve 1-hexadecanol production from xylose at 0.4 g/L. We next applied promoter engineering on the xylose utilization pathway to optimize the expression levels of XR, XDH, and XKS, and increased the 1-hexadecanol titer by 171 %. To further improve the xylose-based fatty alcohol production, two optimized S. cerevisiae strains from promoter engineering were evolved with the xylose as the sole carbon source. We found that the cell growth rate was improved at the expense of decreased fatty alcohol production, which indicated 1-hexadecanol was mainly produced as a non-growth associated product. Finally, through fed-batch fermentation, we successfully achieved 1-hexadecanol production at over 1.2 g/L using xylose as the sole carbon source, which represents the highest titer of xylose-based 1-hexadecanol reported in microbes to date. CONCLUSIONS: A fatty alcohol-producing S. cerevisiae strain was engineered in this study to produce 1-hexadecanol from xylose. Although the xylose pathway we developed in this study could be further improved, this proof of-concept study, for the first time to our best knowledge, demonstrated that the xylose-based fatty alcohol could be produced in S. cerevisiae with potential applications in developing consolidated bioprocessing for producing other fatty acid-derived chemicals. PMID- 26830024 TI - Assessing Chikungunya risk in a metropolitan area of Argentina through satellite images and mathematical models. AB - BACKGROUND: Chikungunya fever is a viral disease that recently invaded the American continent. In America, it is transmitted mainly by the mosquito Aedes aegypti, but Aedes albopictus is the main vector in other regions of the world. This work estimates the risk of disease emergence and the corresponding population at risk for the case of a naive population in the metropolitan area of Buenos Aires, the capital city of Argentina. METHODS: A classic metapopulation epidemiological model, that considers human and mosquito populations, was extended in order to include different environmental signals. First, the vital rates of the mosquitoes were affected by local temperature. Second, habitat availability estimated from satellite images was used to determine the carrying capacity for local mosquito populations. Disease invasion was proposed to occur at different moments of the year. For each scenario, Monte Carlo simulations were used to estimate the risk of disease invasion and the population at risk. RESULTS: The risk of a Chikungunya outbreak displays strong temporal (seasonal) patterns as well as spatial variability at the level of neighborhoods in the study area. According to the model, Summer and Fall display high risk for a Chikungunya invasion. The population at risk displays less variation over the year underlying the importance of preventive actions. CONCLUSIONS: The ability of mapping habitat quality for vector-borne diseases allows developing risk analysis at scales that are easily manageable for public health officers. For this location, the correlation of disease risk with the season of the year and the habitat availability could provide information to develop efficient control strategies. This also underlines the importance of involving the whole community when developing control measures for Chikungunya fever and other recently invading vector-borne diseases such as Zika fever. PMID- 26830025 TI - The intestinal distribution pattern of appetite- and glucose regulatory peptides in mice, rats and pigs. AB - BACKGROUND: Mice, rats, and pigs are the three most used animal models when studying gastrointestinal peptide hormones; however their distribution from the duodenum to the distal colon has not been characterized systematically across mice, rats and pigs. We therefore performed a comparative distribution analysis of the tissue content of the major appetite- and glucose regulatory peptides: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP 1), glucagon-like peptide-1 (GLP-2), oxyntomodulin/glicentin, neurotensin, and peptide YY (PYY) from the duodenum to distal colon in mice (n = 9), rats (n = 9) and pigs (n = 8), using validated radioimmunoassays. RESULTS: GLP-1, GLP-2 and oxyntomodulin/glicentin show similar patterns of distribution within the respective species, but for rats and pigs the highest levels were found in the distal small intestine, whereas for the mouse the highest level was found in the distal colon. In rats and pigs, neurotensin was predominantly detected in mid and lower part of the small intestine, while the mouse showed the highest levels in the distal small intestine. In contrast, the distribution of GIP was restricted to the proximal small intestine in all three species. Most surprisingly, in the pig PYY was found in large amounts in the proximal part of the small intestine whereas both rats and mice had undetectable levels until the distal small intestine. CONCLUSIONS: In summary, the distribution patterns of extractable GIP, GLP-1, GLP-2, oxyntomodulin/glicentin, neurotensin are preserved across species whereas PYY distribution showed marked differences. PMID- 26830027 TI - Insecticide treated nets use and its determinants among settlers of Southwest Ethiopia. AB - BACKGROUND: Ethiopia is rapidly increasing insecticide-treated nets (ITNs) coverage to combat malaria, but adequate follow-up and factors affecting use of ITNs is lacking. The aim of this study was to assess determinants of the use of ITNs in a southwest area of Ethiopia. METHODS: This cross-sectional survey was conducted in the Chewaka district settlement area of southwest Oromia from March to May, 2013. Kebeles were stratified by degree of urbanization (rural, peri urban, or urban). Randomly selected households, which had been freely supplied with at least one ITN, were surveyed using a pre-tested, structured questionnaire administered through household interviews. Logistic regression analysis was used to examine the association between use of ITNs and determinant factors. RESULTS: Of 574 households surveyed, 72.6 % possessed ITNs and 80 % of these had been used the night before the survey. The most common reasons for the absence ITNs in the household identified in this study were ITNs were old and therefore discarded and that households use ITNs for purposes other than their intended use. The multivariate analysis found that knowledge of malaria transmission by mosquito bites (Adjusted OR = 3.44, 95 % CI: 1.80-6.59), and washing of ITNs at least once by households (Adjusted OR = 2.66, 95 % CI: 1.35-5.26) were significantly associated with an ITN being used by households. The mean possession was 1.59 ITN per household (3.57 persons per an ITN). One hundred fifty four (36.9 %) of ITNs had at least one hole/tear. Among these, 108 (70.1 %) ITNs had at least one hole/tear with greater than 2 cm and 29 (18.8 %) had greater than seven holes/tears. CONCLUSIONS: This study in Southwest Ethiopia showed a high proportion of net ownership compared to a household survey from Ethiopia which included in the World Malaria Report. Despite somewhat high percentages ITN ownership, the study demonstrated there was still a gap between ownership and use of ITNs. Use of ITNs was affected by knowledge of malaria transmission by mosquito bite and washing of ITNs at least once by households. Intensive health education and community mobilization efforts should be employed to attempt to influence these factors that significantly affect ITN use. PMID- 26830026 TI - Promoting and maintaining physical activity in the transition to retirement: a systematic review of interventions for adults around retirement age. AB - It has been argued that transition points in life, such as the approach towards, and early years of retirement present key opportunities for interventions to improve the health of the population. Research has also highlighted inequalities in health status in the retired population and in response to interventions which should be addressed. We aimed to conduct a systematic review to synthesise international evidence on the types and effectiveness of interventions to increase physical activity among people around the time of retirement. A systematic review of literature was carried out between February 2014 and April 2015. Searches were not limited by language or location, but were restricted by date to studies published from 1990 onwards. Methods for identification of relevant studies included electronic database searching, reference list checking, and citation searching. Systematic search of the literature identified 104 papers which described study populations as being older adults. However, we found only one paper which specifically referred to their participants as being around the time of retirement. The intervention approaches for older adults encompassed: training of health care professionals; counselling and advice giving; group sessions; individual training sessions; in-home exercise programmes; in-home computer-delivered programmes; in-home telephone support; in-home diet and exercise programmes; and community-wide initiatives. The majority of papers reported some intervention effect, with evidence of positive outcomes for all types of programmes. A wide range of different measures were used to evaluate effectiveness, many were self-reported and few studies included evaluation of sedentary time. While the retirement transition is considered a significant point of life change, little research has been conducted to assess whether physical activity interventions at this time may be effective in promoting or maintaining activity, or reducing health inequalities. We were unable to find any evidence that the transition to retirement period was, or was not a significant point for intervention. Studies in older adults more generally indicated that a range of interventions might be effective for people around retirement age. PMID- 26830028 TI - CD10 expression in the neuroendocrine carcinoma component of endometrial mixed carcinoma: association with long survival. AB - BACKGOUND: Endometrial mixed carcinoma with the neuroendocrine carcinoma (NEC) component is rare and is believed to have a poor prognosis. CD10 expression is reported to be a favorable prognostic marker for some tumors such as B lymphoblastic leukemia/lymphoma, but unfavorable for others. Here, we report the case of a 33-year-old woman diagnosed with endometrial mixed carcinoma with the NEC component expressing CD10 who showed a favorable outcome. CASE PRESENTATION: The patient presented with lumbago and brownish discharge from the genitals. Imaging modalities revealed a large exophytic mass in the uterine corpus, and a small one in the uterine cervix. Radical hysterectomy with bilateral salpingo oophorectomy was performed. Microscopic examination of the endometrial and cervical masses revealed that the NEC component accounted for the maximum area in both masses. However, small areas in both lesions showed well differentiated endometrioid adenocarcinoma (WDEA) components, and histological transition between the two components was also observed. In addition to CD56 and synaptophysin expression, the NEC component was positive for CD10 but negative for estrogen receptor (ER), progesterone receptor (PgR), and carcinoembryonic antigen (CEA). In contrast, the WDEA component expressed both ER and PgR, but neither CD10 nor neuroendocrine markers were demonstrated. The CD10 and neuroendocrine markers clearly distinguished between the NEC and WDEA components. Furthermore, retained expression of phosphatase and tensin homolog (PTEN) and weak phosphorylated Akt expression were found, which were assumed to suppress the aggressive behavior of the tumor. The patient received postoperative chemotherapy and has survived without recurrence for 6 years after the operation. CONCLUSION: This is the first case of endometrial mixed carcinoma with the NEC component expressing CD10 that showed a long survival. PMID- 26830029 TI - Assessing the effectiveness of enhanced psychological care for patients with depressive symptoms attending cardiac rehabilitation compared with treatment as usual (CADENCE): study protocol for a pilot cluster randomised controlled trial. AB - BACKGROUND: Around 17% of people eligible for UK cardiac rehabilitation programmes following an acute coronary syndrome report moderate or severe depressive symptoms. While maximising psychological health is a core goal of cardiac rehabilitation, psychological care can be fragmented and patchy. This study tests the feasibility and acceptability of embedding enhanced psychological care, composed of two management strategies of proven effectiveness in other settings (nurse-led mental health care coordination and behavioural activation), within the cardiac rehabilitation care pathway. METHODS/DESIGN: This study tests the uncertainties associated with a large-scale evaluation by conducting an external pilot trial with a nested qualitative study. We aim to recruit and randomise eight comprehensive cardiac rehabilitation teams (clusters) to intervention (embedding enhanced psychological care into routine cardiac rehabilitation programmes) or control (routine cardiac rehabilitation programmes alone) arms. Up to 64 patients (eight per team) identified with depressive symptoms upon initial assessment by the cardiac rehabilitation team will be recruited, and study measures will be administered at baseline (before starting rehabilitation) and at 5 months and 8 months post baseline. Outcomes include depressive symptoms, cardiac mortality and morbidity, anxiety, health-related quality of life and service resource use. Trial data on cardiac team and patient recruitment, and the retention and flow of patients through treatment will be used to assess intervention feasibility and acceptability. Qualitative interviews will be undertaken to explore trial participants' and cardiac rehabilitation nurses' views and experiences of the trial methods and intervention, and to identify reasons why patients declined to take part in the trial. Outcome data will inform a sample size calculation for a definitive trial. DISCUSSION: The pilot trial and qualitative study will inform the design of a fully powered cluster randomised controlled trial to evaluate the effectiveness and cost effectiveness of the provision of enhanced psychological care within cardiac rehabilitation programmes. TRIAL REGISTRATION: ISRCTN34701576 (Registered 29 May 2014). PMID- 26830030 TI - Accounting for dominance to improve genomic evaluations of dairy cows for fertility and milk production traits. AB - BACKGROUND: Dominance effects may contribute to genetic variation of complex traits in dairy cattle, especially for traits closely related to fitness such as fertility. However, traditional genetic evaluations generally ignore dominance effects and consider additive genetic effects only. Availability of dense single nucleotide polymorphisms (SNPs) panels provides the opportunity to investigate the role of dominance in quantitative variation of complex traits at both the SNP and animal levels. Including dominance effects in the genomic evaluation of animals could also help to increase the accuracy of prediction of future phenotypes. In this study, we estimated additive and dominance variance components for fertility and milk production traits of genotyped Holstein and Jersey cows in Australia. The predictive abilities of a model that accounts for additive effects only (additive), and a model that accounts for both additive and dominance effects (additive + dominance) were compared in a fivefold cross validation. RESULTS: Estimates of the proportion of dominance variation relative to phenotypic variation that is captured by SNPs, for production traits, were up to 3.8 and 7.1 % in Holstein and Jersey cows, respectively, whereas, for fertility, they were equal to 1.2 % in Holstein and very close to zero in Jersey cows. We found that including dominance in the model was not consistently advantageous. Based on maximum likelihood ratio tests, the additive + dominance model fitted the data better than the additive model, for milk, fat and protein yields in both breeds. However, regarding the prediction of phenotypes assessed with fivefold cross-validation, including dominance effects in the model improved accuracy only for fat yield in Holstein cows. Regression coefficients of phenotypes on genetic values and mean squared errors of predictions showed that the predictive ability of the additive + dominance model was superior to that of the additive model for some of the traits. CONCLUSIONS: In both breeds, dominance effects were significant (P < 0.01) for all milk production traits but not for fertility. Accuracy of prediction of phenotypes was slightly increased by including dominance effects in the genomic evaluation model. Thus, it can help to better identify highly performing individuals and be useful for culling decisions. PMID- 26830031 TI - A Droplet Microfluidic Platform for Automating Genetic Engineering. AB - We present a water-in-oil droplet microfluidic platform for transformation, culture and expression of recombinant proteins in multiple host organisms including bacteria, yeast and fungi. The platform consists of a hybrid digital microfluidic/channel-based droplet chip with integrated temperature control to allow complete automation and integration of plasmid addition, heat-shock transformation, addition of selection medium, culture, and protein expression. The microfluidic format permitted significant reduction in consumption (100-fold) of expensive reagents such as DNA and enzymes compared to the benchtop method. The chip contains a channel to continuously replenish oil to the culture chamber to provide a fresh supply of oxygen to the cells for long-term (~5 days) cell culture. The flow channel also replenished oil lost to evaporation and increased the number of droplets that could be processed and cultured. The platform was validated by transforming several plasmids into Escherichia coli including plasmids containing genes for fluorescent proteins GFP, BFP and RFP; plasmids with selectable markers for ampicillin or kanamycin resistance; and a Golden Gate DNA assembly reaction. We also demonstrate the applicability of this platform for transformation in widely used eukaryotic organisms such as Saccharomyces cerevisiae and Aspergillus niger. Duration and temperatures of the microfluidic heat-shock procedures were optimized to yield transformation efficiencies comparable to those obtained by benchtop methods with a throughput up to 6 droplets/min. The proposed platform offers potential for automation of molecular biology experiments significantly reducing cost, time and variability while improving throughput. PMID- 26830032 TI - Synthesis and Cytotoxicity of Two Active Metabolites of Larotaxel. AB - Two epimeric metabolites of Larotaxel were synthesized in eight steps from 10-DAB III as a commercial material and their structures were characterized using NMR and MS spectral data. The cytotoxicity of two metabolites was performed on breast cancer cell lines MCF-7, MX-1 and MDA-MB-231. It is remarkable that both of these two desired taxanes showed great potent cytotoxic effect. PMID- 26830033 TI - The role of local estrogen therapy in the management of pelvic floor disorders. AB - Pelvic floor disorders are common and bothersome problems that include a variety of conditions. These conditions greatly affect the performance of daily activities and social function such as work, traveling, physical exercise, sleep and sexual function. Aging is a well-known factor affecting the pelvic floor and lower urinary tract anatomy and function. It is clear that the pelvic organs and their surrounding muscular and connective tissue support are estrogen-responsive. Treatment of pelvic floor disorders requires significant health-care resources and their impact is likely to increase in the near future. This literature review aims to provide an overview of both research and clinical aspects of the pathophysiology of urogenital estrogen deficiency and the role of local estrogen therapy as part of the management strategy of different pelvic floor disorders. The safety and risk concerns regarding the use of local estrogen therapy are addressed as well. PMID- 26830034 TI - Region-specific differences in colorectal cancer: Slovakia and Hungary have highest incidence in Europe. AB - Epidemiological data on colorectal cancer (CRC) exhibit high incidence in Central East Europe. Hungary, Slovakia and Croatia represent the lead. For decades it was the Czech Republic but it attained the fourth rank after the mid-2000. Remarkably, the Ashkenazi Jews who imigrated to the USA from Central Europe have the highest incidence of CRC among US minorities. They also have high incidence of inflammatory bowel disease, a risk for CRC. Notably, countries surrounding the Central European focus of CRC, Austria, Germany, Poland, Romania, Ukraine and Russia have substantially lower incidence. CRC in Central Europe has higher incidence than CRC among the highest at-risk cohort in the USA, the elderly blacks. Research and the genome wide screening identified genetic mutations associated with CRC in Ashkenazis from Central Europe. Some risk factors for CRC are non genotypic as evidenced by wide variation in CRC incidence in the course of only a few decades. Recent trends offer hope that identification of the non innate pathogenic mechanisms would potentially reduce the burden of this third most lethal malignancy (Tab. 1, Fig. 4, Ref. 40). PMID- 26830035 TI - Stenting of stenotic aortopulmonary collaterals in non-surgically treated adolescent or adult patients with pulmonary atresia, ventricular septal defect and multiple aortopulmonary collaterals. AB - OBJECTIVES: To present our experience with stent implantations in non-surgically treated patients with pulmonary atresia, ventricular septal defect and stenotic aortopulmonary collaterals. METHODS: Between April 2007 and June 2009, 6 stents in 4 patients were implanted into stenosed segments of MAPCAs. The median age and weight of patients at stent implantation were 24 years (range 13-34 years) and 58.5 kg (range 56-70 kg), respectively. RESULTS: All implantations were successfully performed; there were no procedure associated complications. The median diameter increase of stenosed MAPCAs was 107%. The mean arterial blood saturation increased from mean 78% to 84%. An early increase in the median exercise duration measured by 6MWT was 36%. Neointimal in-stent fibroproliferation in 4/6 stents and stent fracture in 1/6 patients occured in mid-term follow-up. CONCLUSION: Percutaneous catheterizational stent implantation into stenosed segments of MAPCAs is a palliative procedure, that might improve quality of life of non-surgically treated patients with PA, VSD, MAPCAs. Neointimal in-stent fibroproliferation and stent fracture can be expected as complications in mid-term follow-up. CT-angiography is recommended to confirm these complications in progressive satO2 decrease (Fig. 3, Ref. 12). PMID- 26830036 TI - Lack of serum antineuronal antibodies in children with autism. AB - OBJECTIVE: Autism spectrum disorders (ASDs) are a severe group of neurodevelopmental disorders that are characterized by impairment in social communication, and imagination and social interaction. The aetiology of autism is complex, but some studies suggest autoimmunity to the central nervous system in the pathogenesis. The aim of this study is to investigate the positivity of antineuronal antibodies including anti-glutamic acid decarboxylase antibodies (anti-GAD), anti-glutamate receptor (anti-GluR) antibodies and seven types of anti-ganglioside antibodies, in children with autism. METHODS: We conducted the study over a period of one year from May 2012 to December 2013. Human anti-GAD in serum were investigated with ELISA; human autoantibodies against the N-methyl-D aspartate subtype of GluR were investigated with indirect immunofluorescence test; class IgG antibodies against the seven gangliosides were investigated with immunoblot assay. RESULTS: Serum antineuronal antibodies were measured in 42 children (24 male, 18 female) with autism in comparison to 21 (13 male, 8 female) healthy-matched children aged between 2-12 years. There was no seropositivity of antineuronal antibodies in either of the groups. CONCLUSION: There is no evidence to support an association between autism and antibodies positivity of anti-GAD, anti-GluR and anti-gangliosides (Ref. 26). PMID- 26830037 TI - Genetic variation in vascular endothelial growth factor gene and its association with recurrent spontaneous abortion. AB - BACKGROUND: Vascular endothelial growth factor (VEGF) plays a main role in fetal and placental angiogenesis and is secreted by different cells of endometrium and placenta. OBJECTIVE: In the present study we investigated the association of VEGF gene polymorphisms with recurrent spontaneous abortion (RSA). METHODS: A case control study of 100 women with at least two consecutive pregnancy losses before 20 weeks of gestational age and 100 fertile controls was performed to evaluate four VEGF gene polymorphisms including +936C/T (rs3025039), -154G>A (rs1570360), rs3025010 and +5092A/C (rs2146323). Genotyping was performed by PCR based restriction fragment length polymorphism (PCR-RFLP) analysis. Haplotype frequency was estimated for three SNPs' genotypes. Analysis of genetic STRUCTURE and K means clustering were performed to estimate genetic variation. RESULTS: We found an association between -154G/A heterozygous genotype (GA) and RSA. The VEGF single nucleotide polymorphism (SNP) in intron region (rs3025010) in different inheritance models was also associated with RSA. Linkage disequilibrium analysis revealed that VEGF SNP in intron 5 (rs3025010) was linked to promoter region SNP (rs1570360). Cluster analysis including Neighbor Joining and K-means clustering supported genetic differentiation of women with RSA and controls. CONCLUSION: Allelic polymorphisms in common VEGF SNPs was associated with RSA samples and haplotypes with at least one minor allele showing an association with RSA pathogenesis (Tab. 8, Fig. 2, Ref. 35). PMID- 26830038 TI - Immune-mediated cochleovestibular disease. AB - OBJECTIVE: The aim of this study is to prove the involvement of the immune response in the etiopathogenesis of some cochleovestibular disorders by a demonstration of antibodies against inner ear antigens and identify the benefits of immunosuppressive therapy. BACKGROUND: McCabe in 1979 postulated the hypothesis of autoimmune inner ear disease. METHODS: Sodium dodecyl sulfate polyacrylamid gel electrophoresis and immunoblotting were used to examine the serum of 74 subjects for the presence of antibodies against inner ear antigens. The subjects were divided into three groups: A--subjects with idiopathic progressive sensorineural hearing loss, B--subjects with Meniere's disease, C- healthy subjects. Individuals with proven antibodies received immunosuppressive therapy. RESULTS: We detected antibodies against inner ear antigens with molecular weight of 30, 50, 60, 80, 100 kDa. In group A they were found in 52% of 25 subjects, in group B in 44% of 25 subjects and they were not detected in group C. An improvement of hearing was recorded in 69% of subjects in group A. An improvement of hearing was observed in 72%, significant relief of vertigo in 81% of subjects in group B. CONCLUSION: The present study supports the hypothesis of immune-mediated cochleovestibular disease (Tab. 3, Ref. 15). PMID- 26830039 TI - Tumor aggressiveness risk factors in the differentiated thyroid carcinoma. AB - BACKGROUND: The differentiated thyroid carcinoma (DTC) is the most frequent malignancy in endocrinology (95%). Our aim was to retrospectively compare risk factors of tumor aggressiveness and history of thyroid disease in patients with conventional DTC and differentiated thyroid microcarcinoma (DTMC). METHODS: Retrospective analysis of 167 patients after total thyroidectomy with a histologically confirmed DTC, of which 83 patients with conventional DTC (> 1 cm) and 84 with DTMC (<= 1 cm). The analyzed factors were tumor size, its aggressiveness (i.e. multifocal or bilateral occurrence, angioinvasion, extracapsular growth, presence of cervical lymph node metastases, distant metastases, and early local relapse) and medical history of thyroid diseases. RESULTS: In the DTMC group, there were 80/84 (95.2%) papillary carcinomas compared with 58/83 (69.9%) in the conventional DTC group (p=0.001). Patients with DTMC were significantly older than those with conventional DTC (p=0.006). In the conventional DTC group, there was a significantly higher occurrence of angioinvasion and extracapsular growth (p=0.001), cervical lymph node metastases (p=0.013), relapse (p=0.018), and distant metastases (p=0.007), compared with the DTMC group. CONCLUSION: In patients with DTMC, there was a significantly lower presence of risk factors of tumor aggressiveness, compared with the conventional DTC group (Tab. 2, Ref. 17). PMID- 26830040 TI - Exercise improves hippocampal estrogen and spatial memory of ovariectomized rats. AB - OBJECTIVE: The present study aimed at examining the effects of regular exercise on hippocampal estrogen and estrogen receptor beta (ERbeta) levels, as well as the spatial memory of ovariectomized rats. BACKGROUND: A decrease of estrogen levels leads to dysfunctions of hippocampus, including spatial learning and memory. Studies have shown that physical exercise improved spatial memory of ovariectomized rats and was associated with an increased extragonadal aromatization. This in turn affects the expression of estrogen receptors. METHODS: Ovariectomized Sprague Dawley rats were randomly assigned into the two groups, i.e. exercise and control groups. Rats of the exercise group were trained to run on a treadmill. The exercise was performed five times per week for 12 weeks. The spatial memory of rats was measured using the Morris water maze. The hippocampal estrogen and ERbeta levels of rats were determined using ELISA. RESULTS: The spatial memory retention of the exercise group was significantly better than that of the control group. The hippocampal estrogen level of the exercise group was significantly higher than that of the control group. CONCLUSION: Regular exercise increases hippocampal estrogen levels and improves spatial memory retention of ovariectomized rats (Tab. 1, Fig. 4, Ref. 53). PMID- 26830041 TI - Antidiabetic and hypolipidemic effects of adropinin streoptozotocin-induced type 2 diabetic rats. AB - BACKGROUND: To examine the effects of adropin on glucose and lipid metabolism in a rat model of Type 2 diabetes mellitus (T2DM). METHODS: T2DM were established using high-fat diet and streptozocin (STZ; 35 mg/kg/b.w.). Seven days after STZ induction, diabetic rats were randomly treated with adropin (2.1 MUg/kg/day intraperitonealy) for 10 days. The study involved the evaluation of biochemical parameters, including blood glucose, total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) activities. Additionally, Tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and inducible nitric oxide synthase (iNOS) mRNA gene expressions in pancreas tissue were determined by reverse transcription-polymerase chain reaction. RESULTS: The serum levels of insulin and adropin were determined by ELISA. Treatment with adropin showed a significant reduction in blood glucose levels, HbA1c (%), HOMA-IR and increase in HOMA-beta, serum insulin levels. In addition, intraperitoneal adropin application can reduce serum levels of TC, TG, LDL-C, and increase level of HDL C. Adropin also effectively ameliorated the alterations in TNF-alpha, IL-6 and iNOS mRNA expression. CONCLUSION: The present study indicates that the adropin possesses antidiabetic and antidyslipidemic effects in T2DM (Tab. 2, Fig. 3, Ref. 32). PMID- 26830042 TI - Co-administration of cisplatin and curcumin does not alter mood-associated behaviors. AB - OBJECTIVES: Cisplatin (cis-diamminedichloroplatinum (II)) is a widely-used platinum-based chemotherapeutic agent which has dose-limiting side-effects. Also, the drug resistance is another instance that decreases treatment success in cisplatin chemotherapy. The growing body of evidence suggests that curcumin, a polyphenolic compound extracted from the spice turmeric, may exert synergistic effects and sensitize malign cells to cisplatin, while alleviating cytotoxicity related side-effects. The present study was aimed to investigate mood-associated interactions between cisplatin and curcumin. MATERIALS AND METHODS: Thirty-four adult male Wistar albino rats were randomly assigned to four groups as control, curcumin (300 mg/kg/day, p.o. for 5 weeks), cisplatin (5 mg/kg/week, i.p. for 5 weeks), and curcumin plus cisplatin (same doses as above). The open field, elevated plus maze, and forced swim tests were engaged to evaluate mood associated behaviors. RESULTS: We demonstrated that depression- and anxiety-like behaviors were not altered by the administration of curcumin along with the chronic cisplatin treatment. CONCLUSION: According to the results of the present study, we concluded that curcumin might be regarded as a safe adjuvant in cisplatin chemotherapy in terms of the mood-associated behaviors (Fig. 4, Ref. 41). PMID- 26830044 TI - Spontaneous regression of multiple pulmonary aneurysms in a patient with midaortic syndrome and arterial hypertension. PMID- 26830043 TI - Clonninger's temperament and character inventory profiles of anatomists: is there a relation with specialty choice? AB - Career psychologists have argued that the career choice and personality interfere with each other. There have been lots of investigations aimed at seeking the relationships between career interests and personality characteristics. There is limited knowledge on personality profiles of the anatomists and on how they are related with their specialty choices. AIM: In this research we aimed to explore the relationship between personality and career interests of anatomists. METHOD: Out of 279 anatomists who had been asked to complete the survey via e-mail including three questionnaires, 79 (53 male, 26 female) responded in the present study. Personality was assessed using the Cloninger's Temperament and Character Inventory (TCI). The career interest was determined by Holland's Theme Codes. RESULTS: The order of high frequency Holland's Codes was as follows: social (44.3%), realistic (35.4%), investigative (27.8%), conventional (19.0%), artistic (7.6%), and enterprising (5.1%). With regard to temperament components of TCI was as follows: novelty seeking (mean=17.7+/-4.7), harm avoidance (mean=13.9+/-6.1), reward dependence (mean=13.2+/-3.4), and persistence (mean=5.4+/-2.1). Character profiles are as follows: self-directedness (mean=33.1+/-6.3), self-transcendence (mean=17.9+/-7.6), and cooperativeness (mean=30.6+/-5.9). According to the last questionnaire, the most important cause for choosing anatomy is the interest in anatomy since medical study time. CONCLUSION: These results in part support Holland's theory, which takes the career as a function of personality and the personality profiles of anatomists have affected the motivation to select their specialty choice partially (Tab. 3, Fig. 1, Ref. 10). PMID- 26830045 TI - Integrated assessment of ceria nanoparticle impacts on the freshwater bivalve Dreissena polymorpha. AB - Exposures in realistic environmental conditions are essential to properly assess the effects of emerging pollutants on ecosystems. While ceria nanoparticles (nCeO2) production and use are expanding quickly, ecotoxicity studies remain very scarce. In this study, we set up experimental systems reproducing a simplified ecosystem to assess the effects of a chronic exposure to citrate-coated nCeO2 (ci CeO2) and bare nCeO2 (ba-CeO2) on the freshwater mussel Dreissena polymorpha using an integrated multibiomarker approach. The fate of nanoparticles was tightly monitored to properly characterize the exposure. Organisms were exposed for 3 weeks and sampled weekly for biomarker analysis. Mussel filter-feeding activity resulted in significant removal of nCeO2 from the water column. At the same time, bioaccumulation was low, reaching its maximum in the first week. Mussels bioaccumulated ci-CeO2 three times more than ba-CeO2, probably due to coating-related differences in their behavior in the water column and in organisms. Meanwhile, biomarker results were integrated and synthesized using linear discriminant analysis, highlighting that pi-glutathione-S-transferase (piGST) mRNA, catalase (CAT) activity and lysosomal system were the most impacted of the seven biomarkers singled out by the discriminant analysis. These biomarker responses indicated that mussels exposed to both forms of nCeO2 were stressed and differentiate from the controls. Moreover, they responded differently to ba-CeO2 and ci-CeO2 exposure. However, biomarkers used in the experimental conditions of this study did not indicate severe nCeO2 toxicity on mussels, as cellular damage biomarkers and mussel filtering activity were left unimpaired. However, further studies are needed to investigate if the slight perturbations observed could lead to populational impacts in the long term. PMID- 26830046 TI - Optimization and evaluation of silk fibroin-chitosan freeze-dried porous scaffolds for cartilage tissue engineering application. AB - Silk fibroin/chitosan blend has been reported to be an attractive biomaterial that provides a 3D porous structure with controllable pore size and mechanical property suitable for tissue engineering applications. However, there is no systematic study for optimizing the ratio of silk fibroin (SF) and chitosan (CS) which seems to influence the scaffold property to a great extent. The present research, therefore, investigates the effect of blend ratio of SF and CS on scaffold property and establishes the optimum value of blend ratio. Among the various blends, the scaffolds with blend ratio of SF/CS (80:20) were found to be superior. The scaffold possesses pore size in the range 71-210 MUm and porosity of 82.2 +/- 1.3%. The compressive strength of the scaffold was measured as 190 +/ 0.2 kPa. The cell supportive property of the scaffold in terms of cell attachment, cell viability, and proliferation was confirmed by cell culture study using mesenchymal stem cells derived from umbilical cord blood. Furthermore, the assessment of glycosaminoglycan secretion on the scaffolds indicates its potentiality toward cartilage tissue regeneration. PMID- 26830048 TI - Corrigendum. PMID- 26830047 TI - Sympathetic-mediated activation versus suppression of the immune system: consequences for hypertension. AB - It is generally well-accepted that the immune system is a significant contributor in the pathogenesis of hypertension. Specifically, activated and pro-inflammatory T-lymphocytes located primarily in the vasculature and kidneys appear to have a causal role in exacerbating elevated blood pressure. It has been proposed that increased sympathetic nerve activity and noradrenaline outflow associated with hypertension may be primary contributors to the initial activation of the immune system early in the disease progression. However, it has been repeatedly demonstrated in many different human and experimental diseases that sympathoexcitation is immunosuppressive in nature. Moreover, human hypertensive patients have demonstrated increased susceptibility to secondary immune insults like infections. Thus, it is plausible, and perhaps even likely, that in diseases like hypertension, specific immune cells are activated by increased noradrenaline, while others are in fact suppressed. We propose a model in which this differential regulation is based upon activation status of the immune cell as well as the resident organ. With this, the concept of global immunosuppression is obfuscated as a viable target for hypertension treatment, and we put forth the concept of focused organ-specific immunotherapy as an alternative option. PMID- 26830049 TI - Erratum. PMID- 26830050 TI - Interventions for sexual dysfunction following treatments for cancer in women. AB - BACKGROUND: The proportion of people living with and surviving cancer is growing. This has led to increased awareness of the importance of quality of life, including sexual function, in those affected by cancer. Sexual dysfunction is a potential long-term complication of many cancer treatments. This includes treatments that have a direct impact on the pelvic area and genitals, and also treatments that have a more generalised (systemic) impact on sexual function.This is an update of the original Cochrane review published in Issue 4, 2007, on interventions for treating sexual dysfunction following treatments for cancer for men and women. Since publication in 2007, there has been an increase in the number of trials for both men and women and this current review critiques only those for women. A review in press will present those for men. OBJECTIVES: To evaluate the effectiveness of interventions for treating sexual dysfunction in women following treatments for cancer. To assess adverse events associated with interventions. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 9), MEDLINE, EMBASE, PsycINFO, AMED, CINAHL, Dissertation Abstracts and the NHS Research Register. The searches were originally run in January 2007 and we updated these to September 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that assessed the effectiveness of a treatment for sexual dysfunction. The trial participants were women who had developed sexual dysfunction as a consequence of a cancer treatment. We sought evaluations of interventions that were pharmaceutical, mechanical, psychotherapeutic, complementary or that involved physical exercise. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data and assessed trial quality. We considered meta-analysis for trials with comparable key characteristics. MAIN RESULTS: Since the original version of this review we have identified 11 new studies in women. The one study identified in the earlier version of this review was excluded in this update as it did not meet our narrower inclusion criteria to include only interventions for the treatment, not prevention, of sexual dysfunction.In total 1509 female participants were randomised across 11 trials. All trials explored interventions following treatment either for gynaecological or breast cancer. Eight trials evaluated a psychotherapeutic or psycho-educational intervention. Two trials evaluated a pharmaceutical intervention and one pelvic floor exercises. All involved heterosexual women. Eight studies were at a high risk of bias as they involved a sample of fewer than 50 participants per trial arm. The trials varied not only in intervention content but in outcome measurements, thereby restricting combined analysis. In the trials evaluating a psychotherapeutic intervention the effect on sexual dysfunction was mixed; in three trials benefit was found for some measures of sexual function and in five trials no benefit was found. Evidence from the other three trials, two on different pharmaceutical applications and one on exercise, differed and was limited by small sample sizes. Only the trial of a pH balanced vaginal gel found significant improvements in sexual function. The trials of pharmaceutical interventions measured harm: neither reported any. Only one psychological intervention trial reported that no harm occurred because of the intervention; the other trials of psychological support did not measure harm. AUTHORS' CONCLUSIONS: Since the last version of this review, the new studies do not provide clear information on the impact of interventions for sexual dysfunction following treatments for cancer in women. The sexual dysfunction interventions in this review are not representative of the range that is available for women, or of the wider range of cancers in which treatments are known to increase the risk of sexual problems. Further evaluations are needed. PMID- 26830051 TI - Atrazine degradation by fungal co-culture enzyme extracts under different soil conditions. AB - This investigation was undertaken to determine the atrazine degradation by fungal enzyme extracts (FEEs) in a clay-loam soil microcosm contaminated at field application rate (5 MUg g(-1)) and to study the influence of different soil microcosm conditions, including the effect of soil sterilization, water holding capacity, soil pH and type of FEEs used in atrazine degradation through a 2(4) factorial experimental design. The Trametes maxima-Paecilomyces carneus co culture extract contained more laccase activity and hydrogen peroxide (H2O2) content (laccase = 18956.0 U mg protein(-1), H2O2 = 6.2 mg L(-1)) than the T. maxima monoculture extract (laccase = 12866.7 U mg protein(-1), H2O2 = 4.0 mg L( 1)). Both extracts were able to degrade atrazine at 100%; however, the T. maxima monoculture extract (0.32 h) achieved a lower half-degradation time than its co culture with P. carneus (1.2 h). The FEE type (p = 0.03) and soil pH (p = 0.01) significantly affected atrazine degradation. The best degradation rate was achieved by the T. maxima monoculture extract in an acid soil (pH = 4.86). This study demonstrated that both the monoculture extracts of the native strain T. maxima and its co-culture with P. carneus can efficiently and quickly degrade atrazine in clay-loam soils. PMID- 26830052 TI - blaCTX-M-15 carried by IncF-type plasmids is the dominant ESBL gene in Escherichia coli and Klebsiella pneumoniae at a hospital in Ghana. AB - Escherichia coli and Klebsiella pneumoniae producing extended-spectrum beta lactamases (ESBLs) are among the most multidrug-resistant pathogens in hospitals and are spreading worldwide. Horizontal gene transfer and spread of high-risk clones are involved in ESBL dissemination. Investigation of the resistance phenotypes of 101 consecutive clinical E. coli (n=58) and K. pneumoniae (n=43) isolated at the Komfo Anokye Teaching Hospital in Ghana over 3 months revealed 63 (62%) with an ESBL phenotype. All 63 had a blaCTX-M gene, and sequence analysis showed that 62 of these were blaCTX-M-15. blaCTX-M-15 was linked to ISEcp1 and orf477Delta in all isolates, and most isolates also carried blaTEM, aac(3)-II, aacA4cr, and/or blaOXA-30 genes on IncF plasmids. XbaI/pulsed-field electrophoresis showed heterogeneity among isolates of both species, suggesting that blaCTX-M-15 dissemination is caused by horizontal gene transfer rather than clonal spread of these species in Ghana. PMID- 26830053 TI - Proposal of a new method for subtyping of Mycobacterium kansasii based upon PCR restriction enzyme analysis of the tuf gene. AB - Within this study, a new, rapid method for subtyping of Mycobacterium kansasii was developed based on the sequence analysis of the tuf gene coding for the Tu (thermo-unstable) elongation factor (EF-Tu). The method involves PCR amplification of ca. 740-bp tuf gene fragment, followed by digestion with the MvaI restriction endonuclease. PMID- 26830054 TI - Establishing the validity of different susceptibility testing methods to evaluate the in vitro activity of amoxicillin-clavulanate against Escherichia coli. AB - Amoxicillin-clavulanate MICs of 160 Escherichia coli isolates with characterized resistance mechanisms were obtained by 2 MIC gradient strip brands, 3 automated systems, and reference ISO microdilution method using EUCAST (fixed 2MUg/mL clavulanate) and CLSI (2:1 ratio) criteria. Discrepancies, mainly obtained with gradient strips, lead to an essential agreement range of 76.2-92.5. PMID- 26830055 TI - Comparative Effect of Contrast Media Type on the Incidence of Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis. AB - BACKGROUND: Iodine contrast media are essential components of many imaging procedures. An important potential side effect is contrast-induced nephropathy (CIN). PURPOSE: To compare CIN risk for contrast media within and between osmolality classes in patients receiving diagnostic or therapeutic imaging procedures. DATA SOURCES: PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and Scopus through June 2015. STUDY SELECTION: Randomized, controlled trials that reported CIN-related outcomes in patients receiving low-osmolar contrast media (LOCM) or iso-osmolar contrast media for imaging. DATA EXTRACTION: Independent study selection and quality assessment by 2 reviewers and dual extraction of study characteristics and results. DATA SYNTHESIS: None of the 5 studies that compared types of LOCM reported a statistically significant or clinically important difference among study groups, but the strength of evidence was low. Twenty-five randomized, controlled trials found a slight reduction in CIN risk with the iso-osmolar contrast media agent iodixanol compared with a diverse group of LOCM that just reached statistical significance in a meta-analysis (pooled relative risk, 0.80 [95% CI, 0.65 to 0.99]; P = 0.045). This comparison's strength of evidence was moderate. In a meta regression of randomized, controlled trials of iodixanol, no relationship was found between route of administration and comparative CIN risk. LIMITATIONS: Few studies compared LOCM. Procedural details about contrast administration were not uniformly reported. Few studies specified clinical indications or severity of baseline renal impairment. CONCLUSION: No differences were found in CIN risk among types of LOCM. Iodixanol had a slightly lower risk for CIN than LOCM, but the lower risk did not exceed a criterion for clinical importance. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. PMID- 26830056 TI - The Ahmed Baerveldt Comparison (ABC) Study: Long-Term Results, Successes, Failures, and Complications. PMID- 26830057 TI - Terrien Marginal Degeneration: Clinical Characteristics and Outcomes. PMID- 26830058 TI - Associations between animal characteristic and environmental risk factors and bovine respiratory disease in Australian feedlot cattle. AB - A prospective longitudinal study was conducted in a population of Australian feedlot cattle to assess associations between animal characteristic and environmental risk factors and risk of bovine respiratory disease (BRD). Animal characteristics were recorded at induction, when animals were individually identified and enrolled into study cohorts (comprising animals in a feedlot pen). Environmental risk factors included the year and season of induction, source region and feedlot region and summary variables describing weather during the first week of follow-up. In total, 35,131 animals inducted into 170 cohorts within 14 feedlots were included in statistical analyses. Causal diagrams were used to inform model building and multilevel mixed effects logistic regression models were fitted within the Bayesian framework. Breed, induction weight and season of induction were significantly and strongly associated with risk of BRD. Compared to Angus cattle, Herefords were at markedly increased risk (OR: 2.0, 95% credible interval: 1.5-2.6) and tropically adapted breeds and their crosses were at markedly reduced risk (OR: 0.5, 95% credible interval: 0.3-0.7) of developing BRD. Risk of BRD declined with increased induction weight, with cattle in the heaviest weight category (>=480kg) at moderately reduced risk compared to cattle weighing <400kg at induction (OR: 0.6, 95% credible interval: 0.5-0.7). Animals inducted into feedlots during summer (OR: 2.4, 95% credible interval: 1.4-3.8) and autumn (OR: 2.1, 95% credible interval: 1.2-3.2) were at markedly increased risk compared to animals inducted during spring. Knowledge of these risk factors may be useful in predicting BRD risk for incoming groups of cattle in Australian feedlots. This would then provide the opportunity for feedlot managers to tailor management strategies for specific subsets of animals according to predicted BRD risk. PMID- 26830059 TI - Cytotoxic activity against human neuroblastoma and melanoma cells mediated by IgM antibodies derived from peripheral blood of healthy donors. AB - A small percentage of healthy donors identified in the Western population carry antibodies in their peripheral blood which convey cytotoxic activity against certain human melanoma and neuroblastoma cell lines. We measured the cytotoxic activity of sera and plasmas from healthy donors on the human neuroblastoma cell line Kelly and various melanoma cell lines. Antibodies of IgM isotype, presumably belonging to the class of naturally occurring antibodies, exerted cytotoxic activity in a complement-dependent fashion. Apart from complement-dependent tumor cell lysis, we observed C3 opsonization in all tumor cell lines upon treatment with cytotoxic plasmas. Cell lines tested primarily expressed membrane complement regulatory proteins (mCRP) CD46, CD55 and CD59 to various extents. Blocking of mCRPs by monoclonal antibodies enhanced cell lysis and opsonization, though some melanoma cells remained resistant to complement attack. Epitopes recognized by cytotoxic antibodies were represented by gangliosides such as GD2 and GD3, as evidenced by cellular sialidase pretreatment and enhanced expression of distinct gangliosides. It remains to be clarified why only a small fraction of healthy persons carry these antitumor cytotoxic antibodies. PMID- 26830060 TI - Effective case/infection ratio of poliomyelitis in vaccinated populations. AB - Recent polio outbreaks in Syria and Ukraine, and isolation of poliovirus from asymptomatic carriers in Israel have raised concerns that polio might endanger Europe. We devised a model to calculate the time needed to detect the first case should the disease be imported into Europe, taking the effect of vaccine coverage - both from inactivated and oral polio vaccines, also considering their differences - on the length of silent transmission into account by deriving an 'effective' case/infection ratio that is applicable for vaccinated populations. Using vaccine coverage data and the newly developed model, the relationship between this ratio and vaccine coverage is derived theoretically and is also numerically determined for European countries. This shows that unnoticed transmission is longer for countries with higher vaccine coverage and a higher proportion of IPV-vaccinated individuals among those vaccinated. Assuming borderline transmission (R = 1.1), the expected time to detect the first case is between 326 days and 512 days in different countries, with the number of infected individuals between 235 and 1439. Imperfect surveillance further increases these numbers, especially the number of infected until detection. While longer silent transmission does not increase the number of clinical diseases, it can make the application of traditional outbreak response methods more complicated, among others. PMID- 26830061 TI - Microparticle image velocimetry approach to flow measurements in isolated contracting lymphatic vessels. AB - We describe the development of an optical flow visualization method for resolving the flow velocity vector field in lymphatic vessels in vitro. The aim is to develop an experimental protocol for accurately estimating flow parameters, such as flow rate and shear stresses, with high spatial and temporal resolution. Previous studies in situ have relied on lymphocytes as tracers, but their low density resulted in a reduced spatial resolution whereas the assumption that the flow was fully developed in order to determine the flow parameters of interest may not be valid, especially in the vicinity of the valves, where the flow is undoubtedly more complex. To overcome these issues, we have applied the time resolved microparticle image velocimetry (MU -PIV) technique, a well-established method that can provide increased spatial and temporal resolution that this transient flow demands. To that end, we have developed a custom light source, utilizing high-power light-emitting diodes, and associated control and image processing software. This paper reports the performance of the system and the results of a series of preliminary experiments performed on vessels isolated from rat mesenteries, demonstrating, for the first time, the successful application of the MU -PIV technique in these vessels. PMID- 26830062 TI - Meta-analysis of antegrade continence enema in adults with faecal incontinence and constipation. AB - BACKGROUND: Faecal incontinence and constipation affects up to 20 per cent of the general population, and can be a significant source of distress. The antegrade continence enema (ACE) procedure has been shown to be an effective alternative treatment option for children, but its use in adults requires clarification. A systematic review and meta-analysis was performed to determine outcomes of the ACE procedure in adults with faecal incontinence and constipation. METHODS: PubMed, MEDLINE and the Cochrane Library (from January 1990 to January 2015) were searched for studies that reported outcomes of ACE in adults with faecal incontinence and constipation. The primary outcome measure was successful use of ACE in the management of symptoms, as determined by continued use at follow-up. RESULTS: Seventeen observational studies involving 426 patients (265 female patients; median age 42 (range 17-84) years) with faecal incontinence (165 patients), constipation (209) or both (52), who had undergone the ACE procedure, were analysed. At a median follow-up of 39 months, the pooled success rate was 74.3 (95 per cent c.i. 66.1 to 82.6) per cent (P < 0.001). For patients with faecal incontinence the pooled success rate was 83.6 (75.0 to 92.1) per cent, compared with 67.7 (55.1 to 80.3) per cent in patients with constipation (both P < 0.001). CONCLUSION: The ACE procedure is an effective long-term treatment option in patients with faecal incontinence and constipation, and should be considered before performing a definitive colostomy. Patients with faecal incontinence appear to respond better than those with constipation. PMID- 26830063 TI - Predicted effect of selectively testing female donors for HLA antibodies to mitigate transfusion-related acute lung injury risk from apheresis platelets. AB - BACKGROUND: The use of male-donor-predominant plasma has reduced the risk of transfusion-related acute lung injury (TRALI), but the possible benefit of different mitigation strategies for other components is unknown. We evaluated the risk of TRALI from apheresis platelets (PLTs) to predict the effect of selectively testing female plateletpheresis donors who have been pregnant for HLA antibodies. STUDY DESIGN AND METHODS: The American Red Cross hemovigilance program classified TRALI cases from apheresis PLTs or red blood cells (RBCs) in 2006 to 2013 or from predominantly male-donor (>95%) plasma in 2008 to 2013 and compared the component-specific TRALI rates. RESULTS: The overall rate of TRALI was significantly higher for apheresis PLTs (6.2 cases per 10(6) units; OR [95% CI], 3.3 [2.3-4.8]) or plasma (3.8 cases per 10(6) units; OR [95% CI], 2.0 [1.4 2.9]) compared to RBCs (1.9 per 10(6) units). Twenty-nine of the 41 apheresis PLT cases involved female donors; 28 had been pregnant, and one had not been pregnant and was not tested. Twenty-five (61%) of the apheresis PLT TRALI cases had female donors with HLA Class I or Class II antibodies. In five of six cases that implicated specific HNA antibodies, the female parous donors also had multiple HLA antibodies. CONCLUSIONS: TRALI was more likely after transfusion of apheresis PLTs than male-donor-predominant plasma or RBCs. A selective strategy to test all female plateletpheresis donors who have been pregnant for HLA antibodies might reduce the risk of TRALI by approximately 60% and prevent some cases from coexisting HNA antibodies. PMID- 26830064 TI - Responses to hyperthermia. Optimizing heat dissipation by convection and evaporation: Neural control of skin blood flow and sweating in humans. AB - Under normothermic, resting conditions, humans dissipate heat from the body at a rate approximately equal to heat production. Small discrepancies between heat production and heat elimination would, over time, lead to significant changes in heat storage and body temperature. When heat production or environmental temperature is high the challenge of maintaining heat balance is much greater. This matching of heat elimination with heat production is a function of the skin circulation facilitating heat transport to the body surface and sweating, enabling evaporative heat loss. These processes are manifestations of the autonomic control of cutaneous vasomotor and sudomotor functions and form the basis of this review. We focus on these systems in the responses to hyperthermia. In particular, the cutaneous vascular responses to heat stress and the current understanding of the neurovascular mechanisms involved. The available research regarding cutaneous active vasodilation and vasoconstriction is highlighted, with emphasis on active vasodilation as a major responder to heat stress. Involvement of the vasoconstrictor and active vasodilator controls of the skin circulation in the context of heat stress and nonthermoregulatory reflexes (blood pressure, exercise) are also considered. Autonomic involvement in the cutaneous vascular responses to direct heating and cooling of the skin are also discussed. We examine the autonomic control of sweating, including cholinergic and noncholinergic mechanisms, the local control of sweating, thermoregulatory and nonthermoregulatory reflex control and the possible relationship between sudomotor and cutaneous vasodilator function. Finally, we comment on the clinical relevance of these control schemes in conditions of autonomic dysfunction. PMID- 26830065 TI - Foregut duplication cyst of the floor of mouth in a neonate: case report. AB - Congenital oral masses may interfere with vital functions such as respiration and deglutition in neonates. We report a congenital heterotopic oral gastrointestinal cyst that caused failure to thrive. A working knowledge of the differential diagnosis and pathophysiology of this can guide the clinician in its evaluation and management. PMID- 26830066 TI - Radioprotective effects of lycopene and curcumin during local irradiation of parotid glands in Sprague Dawley rats. AB - Radiotherapy effectively treats cancers of the head and neck. We investigated the possible protective effects of lycopene and curcumin on the parotid glands of 40 female Sprague Dawley rats during irradiation. The study followed European Union regulations 86/609/EEC, 2010/63/EU for animal experimentation. The animals were divided into 4 groups: those treated with curcumin and radiation, those treated with lycopene and radiation, those treated with dimethyl sulphoxide (DMSO) and radiation, and those treated with radiation alone. All compounds were given intraperitoneally the day before irradiation. The total dose of radiation was 20Gy. Morphological and histopathological analyses showed less cell necrosis in the group treated with curcumin than in the other groups, but the difference was not significant. Analysis of structural damage to the parotid ducts and vacuolisation showed significant differences among all groups (p=0.023, p<0.01). Lycopene and curcumin given 24 hours before irradiation reduced the structural damage to the salivary glands. Further studies are needed to confirm these findings. PMID- 26830067 TI - Modification to facilitate the wearing of spectacles by patient after reconstruction with a paramedian forehead pedicled flap. PMID- 26830068 TI - Cervical silicone lymphadenopathy. AB - A patient presented to the department of oral and maxillofacial surgery with a rare case of cervical silicone lymphadenopathy. She had a painless ovoid mass in the left side of her neck and had had cosmetic breast augmentation 10 years before. Radiological imaging and core biopsy examination were consistent with silicone lymphadenopathy. PMID- 26830070 TI - Regarding: Advances in hepatectomy technique: Toward zero transfusions in the modern era of liver surgery. PMID- 26830069 TI - Hospital-skilled nursing facility referral linkage reduces readmission rates among Medicare patients receiving major surgery. AB - BACKGROUND: In the health reform era, rehospitalization after discharge may result in financial penalties to hospitals. The effect of increased hospital skilled nursing facility (SNF) linkage on readmission reduction after surgery has not been explored. METHODS: To determine whether enhanced hospital-SNF linkage, as measured by the proportion of surgical patients referred from a hospital to a particular SNF, would result in reduced 30-day readmission rates for surgical patients, we used national Medicare data (2011-2012) and evaluated patients who underwent 1 of 5 operative procedures (coronary artery bypass grafting [CABG], hip fracture repair, total hip arthroplasty, colectomy, or lumbar spine surgery). Initial evaluation was performed using regression modeling. Patient choice in SNF referral was adjusted for using instrumental variable (IV) analysis with distance between an individuals' home and the SNF as the IV. RESULTS: A strong negative correlation (P < .001) was observed between the proportion of selected surgical discharges received by a SNF and the rate of hospital readmission. Increasing the proportion of surgical discharges decreased the likelihood of rehospitalization (regression coefficient, -0.04; 95% CI, -0.07 to -0.02). These findings were preserved in IV analysis. Increasing hospital-SNF linkage was found to reduce significantly the likelihood of readmission for patients receiving lumbar spine surgery, CABG, and hip fracture repair. CONCLUSION: The benefits of increased hospital-SNF linkage seem to include meaningful reductions in hospital readmission after surgery. Overall, a 10% increase in the proportion of surgical referrals to a particular SNF is estimated to decrease readmissions by 4%. This may impact hospital-SNF networks participating in risk-based reimbursement models. PMID- 26830071 TI - Mesenchymal stem cells enhance lung recovery after injury, shock, and chronic stress. AB - BACKGROUND: Normal lung healing is impaired when lung contusion (LC) is followed by hemorrhagic shock (HS), and chronic stress (CS). Mesenchymal stem cells (MSCs) are immunomodulatory, pluripotent cells that are under investigation for use in wound healing and tissue regeneration. We hypothesized that treatment with MSCs can reverse the impaired healing seen after LC combined with HS and CS (LCHS/CS). METHODS: Male Sprague-Dawley rats (n = 6/group) underwent LCHS with or without a single intravenous dose of 5 * 10(6) Sprague-Dawley rat MSCs after resuscitation. Thereafter, rats were subjected to 2 hours of CS daily on days 1-6 and were humanely killed on day 7. Lung histology was scored according to a well established lung injury score (LIS) that included interstitial and pulmonary edema, alveolar integrity, and inflammatory cells. Scoring ranges from 0 (normal lung) to 11 (most severely injured). Whole blood was analyzed for the presence of CD4(+)CD25(+)FoxP3(+) T-regulatory cells (Treg) by flow cytometry. RESULTS: Seven days after isolated LC, LIS had returned to 0.8 +/- 0.4; however, after LCHS/CS healing is significantly delayed (7.2 +/- 2.2; P < .05). Addition of MSC to LCHS/CS decreased LIS to 2.0 +/- 1.3 (P < .05) and decreased all subgroup scores (inflammatory cells, interstitial and pulmonary edema, and alveolar integrity) significantly compared with LCHS/CS (P < .05). The percentage of Tregs found in the peripheral blood of animals undergoing LCHS/CS did not change from LC alone (10.5 +/- 3.3% vs 6.7 +/- 1.7%; P > .05). Treatment with MSCs significantly increased the Treg population compared with LCHS/CS alone (11.7 +/- 2.7% vs 6.7 +/- 1.7%; P < .05) CONCLUSION: In this model, severe impairment of wound healing observed 1 week after LCHS/CS is reversed by a single treatment with MSCs immediately after resuscitation. This improvement in lung healing is associated with a decrease in the number of inflammatory cells and lung edema and a significant increase in peripheral Tregs. Further study into the timing of administration and mechanisms by which cell-based therapy using MSCs modulate the immune system and improve wound healing is warranted. PMID- 26830072 TI - Suturing the gender gap: Income, marriage, and parenthood among Japanese Surgeons. AB - BACKGROUND: In Japan, gender inequality between males and females in the medical profession still exists. We examined gender gaps in surgeons' incomes. METHODS: Among 8,316 surgeons who participated in a 2012 survey by the Japan Surgical Society, 546 women and 1,092 men within the same postgraduation year were selected randomly with a female-to-male sampling ratio of 1:2 (mean age, 36 years; mean time since graduation, 10.6 years). RESULTS: Average annual income was 9.2 million JPY for women and 11.3 million JPY for men (P < .0001). A general linear regression model showed that the average income of men remained 1.5 million JPY greater after adjusting for gender, age, marital status, number of children, number of beds, current position, and working hours (Model 1). In Model 2, in which 2 statistical interaction terms between annual income and gender with marital status and number of children were added together with variables in Model 1, both interactions became significant, and the gender effect became nonsignificant. For men, average annual income increased by 1.1 million JPY (P < .0001) when they were married and by 0.36 million JPY per child (P = .0014). In contrast, for women, annual income decreased by 0.73 million JPY per child (P = .0005). CONCLUSIONS: Male surgeons earn more than female surgeons, even after adjusting for other factors that influenced a surgeon's salary. In addition, married men earn more than unmarried men, but no such trend is observed for women. Furthermore, as the number of children increases, annual income increases for men but decreases for women. PMID- 26830073 TI - [Comparison between patients undergoing Fontan operation with or without cardiopulmonary bypass]. AB - Fontan operation is the final palliative stage of patients with univentricular hearts. Cardiopulmonary bypass (CPB) decreases ventricular performance and increases pulmonary artery pressures in the post operative recovery period. It seems that Fontan operation performed without CPB decreases short term morbidity and intra hospitalary length of stay. OBJETIVE: Compare outcome in Fontan patients who have undergone surgery with or without CPB. METHOD: This is a retrospective review of patients undergoing Fontan operation from january 2009 to december 2012. Patients were grouped according to CPB use and comparative analyses were done. RESULTS: Ten patients were operated without CPB use. There was a discrepancy between age in both groups, being younger in the no CPB group. Around 80% of patients in both groups had a staged procedure. A 18mm graft was used in half of the cases; a fenestration was created in all cases. Length of stay was equal in both groups, there was less need of pharmacologic support and nitric oxide use in patients without CPB use. No deaths were reported also in this group. At folllow up, most patients had a class i functional status. CONCLUSIONS: In our experience, Fontan operation without CPB has similar outcomes compared with CPB use. PMID- 26830074 TI - Strategies for glucose control in a study population with diabetes, renal disease and anemia (Treat study). AB - Glucose lowering medication use among patients with type 2 diabetes and advanced renal disease (eGFR<60) in a large multinational outcome trial (TREAT) is assessed. We demonstrate statistically significant differences regionally in use of metformin at lower eGFR and increasing reliance upon insulin with/without other medications at low eGFR. INTRODUCTION: As renal disease advances, most of the oral anti-diabetic agents requiring renal clearance must be reduced or discontinued. The potential for prolonged hypoglycemia, fluid/volume overload and congestive heart failure may complicate medication choices. In order to evaluate patterns of glycemia management we describe glucose lowering medication use among patients with advanced renal disease and type 2 diabetes in a large multinational outcome trial designed to focus on patients with eGFR<60 in order to commence a dialog on best practices. We felt that analysis of this data would be able to describe regional variations in treatment within a multinational trial in order to understand potential outcome differences attributed to complications. RESULTS: The patients entering this study had moderate glycemic control. Insulin therapy either alone (32%) or in combination with other agents (17%) reflected a shift towards insulin use in those subjects with decreased renal function when compared with standard populations with normal kidney function. The use of multiple oral agents, or oral agents plus insulin was quite common. While gender did not appear to play a role in medication choices, there were significant regional variations. For example, oral agents were used more in North America compared with other regions (Latin America, Australia/Western Europe, Russia/Eastern Europe). Patients enrolled at more advanced ages were less likely to be on a regimen of rapid-acting insulin alone consistent with recommendations that suggest a preference for longer-acting preparations in the geriatric population (1). Higher degrees of obesity were associated more complex treatment regimens. Despite this population being at high risk for cardiovascular events, the use of beta blockers (50%), statins (64%) and aspirin (48%) were relatively low, especially in the group that did not require medications to achieve adequate glycemic control. CONCLUSIONS: Current attempts to compare strategies for diabetes therapy must control for baseline demographic group differences influencing treatment choice. Future recommendations for glycemic control in patients with Grade 3 or higher chronic kidney disease require additional studies, with matched populations. We suggest that evaluation of studies similar to TREAT will assist in determining the optimal therapeutic regimens for populations with moderate to severe renal dysfunction, a condition in which repeated hospitalizations for fluid overload/heart failure add to the high cost of diabetes care. PMID- 26830075 TI - Trends in type 2 diabetes prevalence according to income levels in Korea (1998 2012). AB - There was no significant association between diabetes prevalence and income levels for either sex in 1998. However, the high income level in men and the low income level in women positively related to the odds of diabetes in 2011-2012. Preventive strategies for diabetes should consider the gender-specific economic discrepancy. PMID- 26830076 TI - Genetic risk of type 2 diabetes in populations of the African continent: A systematic review and meta-analyses. AB - BACKGROUND: Type 2 diabetes (T2D) is growing faster in Africa than anywhere else, driven by the dual effects of genetic and environmental factors. We conducted a systematic review and meta-analyses of published studies on genetic markers of T2D in populations within Africa. METHODS: Multiple databases were searched for studies of genetic variants associated with T2D in populations living in Africa. Studies reporting on the association of a genetic marker with T2D or indicators of glycaemia were included. Data were extracted on study design and characteristics, genetic determinants, effect estimates of associations with T2D. FINDINGS: Overall, 100 polymorphisms in 57 genes have been investigated in relation with T2D in populations within Africa, in 60 studies. Almost all studies used the candidate gene approach, with >88% published during 2006-2014 and 70% (42/60) originating from Tunisia and Egypt. Polymorphisms in ACE, AGRP, eNOS, GSTP1, HSP70-2, MC4R, MTHFR, PHLPP, POL1, TCF7L2, and TNF-alpha gene were found to be associated with T2D, with overlapping effect on various cardiometabolic traits. The polymorphisms investigated in multiple studies mostly had consistent effects across studies, with only modest or no statistical heterogeneity. Effect sizes were modestly significant [e.g., odd ratio 1.49 (95%CI 1.33-1.66) for TCF7L2 (rs7903146)]. Underpowered genome-wide studies revealed no diabetes risk loci specific to African populations. INTERPRETATION: Current evidence on the genetic markers of T2D in African populations mostly originate from North African countries, is overall scanty and largely insufficient to reliably inform the genetic architecture of T2D across Africa. PMID- 26830077 TI - Dynamic interfacial properties of human tear-lipid films and their interactions with model-tear proteins in vitro. AB - This review summarizes the current state of knowledge regarding interfacial properties of very complex biological colloids, specifically, human meibum and tear lipids, and their interactions with proteins similar to the proteins found in aqueous part of human tears. Tear lipids spread as thin films over the surface of tear-film aqueous and play crucial roles in tear-film stability and overall ocular-surface health. The vast majority of papers published to date report interfacial properties of meibum-lipid monolayers spread on various aqueous sub phases, often containing model proteins, in Langmuir trough. However, it is well established that natural human ocular tear lipids exist as multilayered films with a thickness between 30 and 100nm, that is very much disparate from 1 to 2nm thick meibum monolayers. We employed sessile-bubble tensiometry to study the dynamic interfacial and rheological properties of reconstituted multilayered human tear-lipid films. Small amounts (0.5-1MUg) of human tear lipids were deposited on an air-bubble surface to produce tear-lipid films in thickness range 30-100nm corresponding to ocular lipid films. Thus, we were able to overcome major Langmuir-trough method limitations because ocular tear lipids can be safely harvested only in minute, sub-milligram quantities, insufficient for Langmuir through studies. Sessile-bubble method is demonstrated to be a versatile tool for assessing conventional synthetic surfactants adsorption/desorption dynamics at an air-aqueous solution interface. (Svitova T., Weatherbee M., Radke C.J. Dynamics of surfactant sorption at the air/water interface: continuous-flow tensiometry. J. Colloid Interf. Sci. 2003;261:1170-179). The augmented flow-sessile-bubble setup, with step-strain relaxation module for dynamic interfacial rheological properties and high-precision syringe pump to generate larger and slow interfacial area expansions-contractions, was developed and employed in our studies. We established that this method is uniquely suitable for examination of multilayered lipid-film interfacial properties. Recently it was compellingly proven that chemical composition of human tear lipids extracted from whole tears is substantially different from that of meibum lipids. To be exact, healthy human tear lipids contain 8-16% of polar lipids, similar to lung lipids, and they are mostly double-tailed phospholipids, with C16 and longer alkyl chains. Rationally, one would assume that the results obtained for meibum lipids, devoid of surface active components such as phospholipids, and, above all, in a form of monolayers, are not pertinent or useful for elucidating behavior and stability of an averaged 60-nm thick ocular tear-lipid films in vivo. The advantage of sessile-bubble technique, specifically, using a small amount of lipids required to attain multilayered films, unlocks the prospect of evaluating and comparing the interfacial properties of human tear lipids collected from a single individual, typically 100-150MUg. This is in sharp contrast with several milligrams of lipids that would be required to build equally thick films for Langmuir-trough experiments. The results of our studies provided in-depth understanding of the mechanisms responsible for properties and stability of human tear-lipid films in vivo. Here we summarize recent publications and our latest findings regarding human tear-lipid interfacial properties, their chemical composition, and their interaction with model proteins mimicking the proteins found in human tear aqueous phase. PMID- 26830078 TI - Correlation of UGT1A1(*)28 and (*)6 polymorphisms with irinotecan-induced neutropenia in Thai colorectal cancer patients. AB - UDP-glucuronosyltransferase1A1 (UGT1A1) polymorphisms have been related with irinotecan toxicity. The purpose of this study was to determine the associations between UGT1A1(*)28 and (*)6 polymorphisms and irinotecan toxicity in Thai patients with metastatic colorectal cancer. 44 metastatic colorectal cancer patients received irinotecan-based chemotherapy. Hematologic toxicities were determined in the first and second cycles of treatment. The genotypes of UGT1A1(*)28 and (*)6 were analyzed by pyrosequencing technique. The frequencies of genetic testing for UGT1A1(*)28 and (*)6 polymorphisms were 22.8% (TA6/TA7; 20.5%, TA7/TA7; 2.3%) and 15.9% (GA), respectively. No patients had the homozygous UGT1A1(*)6 (AA). Neither UGT1A1(*)28 nor UGT1A1(*)6 polymorphisms were significantly associated with severe hematologic toxicities. However, analysis of UGT1A1(*)28 and (*)6 in combination revealed an association with severe neutropenia in the first and second cycles (P = 0.044, P = 0.017, respectively). Both UGT1A1(*)28 and (*)6 polymorphisms may have an increased risk of irinotecan induced neutropenia in Thai colorectal cancer patients. PMID- 26830079 TI - Fully validated LCMS bioanalysis of Bevacizumab in human plasma using nano surface and molecular-orientation limited (nSMOL) proteolysis. AB - The chemistry of nano-surface and molecular-orientation limited (nSMOL) proteolysis is the Fab-selective limited proteolysis by making use the difference of protease nanoparticle diameter (200 nm) and antibody resin pore diameter (100 nm). In this report, we have demonstrated that the full validation for Bevacizumab bioanalysis in human plasma using nSMOL. The immunoglobulin fraction was collected by Protein A resin from plasma, then nSMOL reaction was performed using the FG nanoparticle-immobilized trypsin under the nondenaturing physiological condition at 50 degrees C for 6 h. After removal of resin and nanoparticles, the signature peptide of Bevacizumab complementarity-determining region (CDR) and internal standard P14R were simultaneously quantified by LCMS multiple reaction monitoring (MRM). This nSMOL method quantification of Bevacizumab showed sensitivity of 0.146 MUg/ml and linearity of 0.146-300 MUg/ml. The intra- and inter-assay precision of lower limit of quantification (LLOQ), low quality control (LQC), middle quality control (MQC), and high quality control (HQC) was 7.94-15.2% and 14.6%, 7.15-13.5% and 11.7%, 2.63-6.47% and 5.83%, and 3.09-4.35% and 4.45%, respectively. These results indicate that nSMOL is also significant method for Bevacizumab bioanalysis in human plasma. PMID- 26830080 TI - Investigation of utility of cerebrospinal fluid drug concentration as a surrogate for interstitial fluid concentration using microdialysis coupled with cisternal cerebrospinal fluid sampling in wild-type and Mdr1a(-/-) rats. AB - In drug discovery, the cerebrospinal fluid (CSF) drug concentration (CCSF) has been used as a surrogate for the interstitial fluid (ISF) concentration (CISF). However, the CCSF-to-CISF gradient suggested for P-glycoprotein (P-gp) substrates in rodents causes uncertainty in CISF estimations and subsequent pharmacokinetic pharmacodynamic analyses. To evaluate the utility of CCSF as a surrogate for CISF, this study directly compared the CCSF with the CISF of 12 compounds, including P-gp substrates, under steady-state conditions in wild-type and Mdr1a( /-) rats using microdialysis coupled with cisternal CSF sampling. In wild-type rats, the ISF-to-unbound plasma (Kp,uu,ISF) and CSF-to-unbound plasma (Kp,uu,CSF) concentration ratios of the P-gp substrates, except for metoclopramide, were lower than those of the non-P-gp substrates, and the Kp,uu,CSF values were within or close to 3-fold of the Kp,uu,ISF values for all the compounds examined. The Kp,uu,CSF values of the selected P-gp substrates increased in Mdr1a(-/-) rats with a similar magnitude to the Kp,uu,ISF values, resulting in the Kp,uu,CSF-to Kp,uu,ISF ratios being unchanged. These results suggested that P-gp-mediated active efflux at the blood-brain barrier is a major determinant not only for CISF, but also for CCSF, and that CCSF can be used as a surrogate for CISF even for P-gp substrates in rats. PMID- 26830081 TI - Pharmacokinetics of catechols in human subjects intravenously receiving XueBiJing injection, an emerging antiseptic herbal medicine. AB - XueBiJing injection, prepared from a five-herb combination, is extensively used as add-on therapy in routine sepsis care in China. Catechols, derived from the component herb Salvia miltiorrhiza roots (Danshen), are probably important because of their reported antiseptic properties. This study was designed to characterize pharmacokinetics of major circulating Danshen catechols in human subjects intravenously receiving the injection at the label doses. A total of 17 Danshen catechols were detected in XueBiJing injection (content level, 0.1-139.3 MUmol/L). After dosing, tanshinol and salvianolic acid B exhibited relatively high levels of systemic exposure with mean elimination half-lives of 0.38 and 0.29 h, respectively. The total plasma clearance and apparent volume of distribution at steady state of tanshinol were 1.07 L/h/kg and 0.40 L/kg, respectively, whereas those of salvianolic acid B were 0.43 L/h/kg and 0.13 L/kg, respectively. Protocatechuic acid and five other catechols were also detected in plasma but at low exposure levels. Although protocatechuic aldehyde had the highest content level in the injection, like the remaining eight catechols, it was undetected in plasma. Protocatechuic aldehyde was extensively converted into protocatechuic acid and other metabolites. The information gained here facilitates understanding the roles of Danshen catechols in therapeutic actions of XueBiJing injection. PMID- 26830082 TI - Functional expression of nicotine influx transporter in A549 human alveolar epithelial cells. AB - Nicotine is a potent addictive alkaloid, and is rapidly absorbed through the alveoli of the lung. However, the transport mechanism of nicotine at the human alveolar epithelial barrier has not been investigated in great detail. In the present study, the transport mechanism of nicotine across alveolar epithelium was investigated in vitro using A549 cells, a human adenocarcinoma-derived cell line with an alveolar epithelial cell like phenotype. Nicotine uptake by A549 cells exhibited time-, temperature-, and concentration-dependence with a Km of 50.4 MUM. These results suggest that a carrier-mediated transport process is involved in nicotine transport in human alveolar epithelial cells. Nicotine uptake by A549 cells was insensitive to change in extracellular pH. Moreover, nicotine uptake by A549 cells could be inhibited by organic cations such as verapamil and pyrilamine, but not typical substrates of organic cation transporters and beta2 agonist. These results suggest that a novel, not yet molecularly identified, organic cation transporter plays a role in nicotine transport which is unlikely to interact with beta2-agonist transport. This nicotine influx transporter in human alveolar epithelium might have implications for the rapid absorption of nicotine into the systemic circulation. PMID- 26830083 TI - The determination of elements in herbal teas and medicinal plant formulations and their tisanes. AB - Elemental analysis of herbal teas and their tisanes is aimed at assessing their quality and safety in reference to specific food safety regulations and evaluating their nutritional value. This survey is dedicated to atomic spectroscopy and mass spectrometry element detection methods and sample preparation procedures used in elemental analysis of herbal teas and medicinal plant formulations. Referring to original works from the last 15 years, particular attention has been paid to tisane preparation, sample matrix decomposition, calibration and quality assurance of results in elemental analysis of herbal teas by different atomic and mass spectrometry methods. In addition, possible sources of elements in herbal teas and medicinal plant formulations have been discussed. PMID- 26830084 TI - Initial [18F]FDG PET/CT in high-risk DTC patients. A three-year follow-up. AB - In a previous paper, we published the impact of initial [18F]FDG PET/CT (FDG PET/CT) in high-risk patients with differentiated thyroid cancer (DTC) and described the changes in therapy management. The aim of the present study was to evaluate the prognostic impact of the initial FDG-PET/CT on a patient's follow-up over three years and the rate of complete remission. PATIENTS, METHODS: This study included 109 DTC patients who underwent radioiodine treatment (RIT), including post-therapeutic whole-body scintigraphy with FDG-PET/CT and a follow up over three years. The follow-up included high-resolution sonography of the neck and determination of serum Tg as well as Tg antibodies every six months. The results of initial FDG-PET/CT and whole-body scintigraphy were compared with the status after three years of follow-up. RESULTS: 24/109 patients (22%) presented FDG-positive lesions, 22/109 patients (20%) only iodine-positive lesions, and 63/109 patients (58%) neither FDG-positive nor iodine-positive lesions. After three years, 83/109 patients (76%) revealed full remission, 15/109 patients (14%) tumour persistence and 11/109 patients (10%) a progressive disease. The negative predictive value (NPV) was calculated for patients without FDG-positive lesions (NPV 85%) and patients without any lesions (NPV 91%) regarding full remission in the follow-up. CONCLUSION: FDG-PET/CT has a high NPV (85% to 91%) in DTC patients regarding recurrence-free follow-up after three years. The change in patient management in patients with iodine-negative lesions can lead to a higher rate of full remissions in the follow-up after additional surgery. Therefore, FDG-PET/CT should be performed in all high-risk DTC patients in the context of the first RIT to improve patient management and risk stratification. PMID- 26830085 TI - CD47: a potential immunotherapy target for eliminating cancer cells. AB - The relationship between the immune system and cancer growth and aggravation has been discussed over a century. A number of molecules have been shown to participate in this process. CD47, a normal universally expressed member of the immunoglobulin superfamily, plays multiple functions in immune system. Researches demonstrated that CD47 was also highly expressed on the surface of tumor cells as well as cancer stem cells (CSCs). Whether the highly expressed CD47 was associated with tumor growth, metastasis, recurrence, or drug resistance has become the hotspot. Besides the roles of CD47 in tumor immunoregulation, the monoclonal antibodies targeting CD47 used in acute myelogenous leukemia (AML) and bladder CSCs were reported, which shed new light on tumor treatment. CSCs have been recognized as the root of tumor drug resistance and recurrence. Whether CD47 on CSCs could serve as a potential target for future anti-cancer treatment forms the focus of our review. Here we highlight the potential roles of CD47 in immune system, and discuss the promising therapeutic application of anti-CD47 antibodies for eliminating tumor cells. PMID- 26830087 TI - The ecological assessment of unilateral neglect. AB - Conventional paper-and-pencil tests of unilateral neglect are of limited ecological validity. To address this issue, a number of assessment procedures have been proposed to provide clinicians and researchers with more ecologically valid assessments of unilateral neglect, which may be useful to plan rehabilitation and to measure the generalization of the effects of rehabilitation to daily life. We present here an overview of the different assessment measures available in the literature. The most widely used scales are the Behavioural Inattention Test (BIT), the semi-structured scales for assessment of personal and extra-personal neglect, the Subjective Neglect Questionnaire, the Baking Tray Task, the wheelchair obstacle course, the ADL-based neglect battery, and the Catherine Bergego Scale (CBS). The CBS is probably, to date, the most widely used behavioural assessment instrument for unilateral neglect. It has been found to be reliable, valid, and sensitive to change during rehabilitation. It also enables the assessment of awareness of the consequences of unilateral neglect in daily life skills. PMID- 26830086 TI - Richter Syndrome in Chronic Lymphocytic Leukemia. AB - The term Richter syndrome (RS) indicates the transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma. RS is a rare complication with an aggressive clinical course, bearing an unfavorable prognosis. In the majority of cases, CLL transforms into RS as diffuse large B cell lymphoma (DLBCL), and a clonal relation between the two processes can be found. However, clonally unrelated RS can occur and transformations to other histologies beside DLBCL have been described. Recent data have shed some light on genetic characteristics that can influence and drive the transformation from CLL to RS. This molecular information has not been translated yet into significant treatment advances, and currently the therapy regimens for RS continue to rely on intensive chemotherapy combinations followed by stem cell transplant in suitable candidates. Based on the rapid pace of discoveries in the field of hematological malignancies and on the recent revolution in the therapeutic landscape for CLL and B cell lymphomas, new therapeutic options for RS might be available in the upcoming years. PMID- 26830088 TI - Enhancing tumor apparent diffusion coefficient histogram skewness stratifies the postoperative survival in recurrent glioblastoma multiforme patients undergoing salvage surgery. AB - Objective To determine the value of apparent diffusion coefficient (ADC) histogram parameters for the prediction of individual survival in patients undergoing surgery for recurrent glioblastoma (GBM) in a retrospective cohort study. Methods Thirty-one patients who underwent surgery for first recurrence of a known GBM between 2008 and 2012 were included. The following parameters were collected: age, sex, enhancing tumor size, mean ADC, median ADC, ADC skewness, ADC kurtosis and fifth percentile of the ADC histogram, initial progression free survival (PFS), extent of second resection and further adjuvant treatment. The association of these parameters with survival and PFS after second surgery was analyzed using log-rank test and Cox regression. Results Using log-rank test, ADC histogram skewness of the enhancing tumor was significantly associated with both survival (p = 0.001) and PFS after second surgery (p = 0.005). Further parameters associated with prolonged survival after second surgery were: gross total resection at second surgery (p = 0.026), tumor size (0.040) and third surgery (p = 0.003). In the multivariate Cox analysis, ADC histogram skewness was shown to be an independent prognostic factor for survival after second surgery. Conclusion ADC histogram skewness of the enhancing lesion, enhancing lesion size, third surgery, as well as gross total resection have been shown to be associated with survival following the second surgery. ADC histogram skewness was an independent prognostic factor for survival in the multivariate analysis. PMID- 26830089 TI - In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue. AB - High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflexTM Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining. PMID- 26830090 TI - Is a modification of the radiotherapeutic target volume necessary after resection of glioblastomas with opening of the ventricles? AB - Extensive surgical resection of centrally localized, newly diagnosed glioblastoma can lead to opening ventricles and therefore carries a potential risk of spreading tumor cells into the cebrospinal fluid. However, whether ventricle opening consequently implies a greater frequency of distant tumor recurrence after radiation therapy-and, therefore, reduced survival-remains unknown. Therefore, is an adaption of target volumes in radiation therapy necessary to account for a potential tumor cell spread into the ventricle system? The present study assessed the resection statuses of 311 primary-glioblastoma patients who underwent radiation therapy. Overall, in 78 cases (25.1 %) the ventricle system was opened during surgical resection. This study assessed the connection between ventricle opening and progression-free survival, overall survival, and distant and multifocal recurrence. OS rates of patients that underwent gross total resection were superior to patients with subtotal resection (p = 0.002). PFS (p = 0.53) and OS (p = 0.18) did not differ due to ventricle opening during surgical resection. However, in a subsample of STR cases increased survival was observed when the ventricle system was opened (16.8 vs. 14.3 months; p = 0.03). The occurrence of distant (p = 0.75) and contralateral recurrence (p = 0.87) was not influenced by ventricle opening. Newly diagnosed glioblastoma patients whose ventricle systems were opened during microsurgical resection did not experience decreased survival or show increased likelihoods of distant and contralateral progressions following radiation therapy. In short, patients profit from surgical resections that are as extensive as reasonably possible, even if this entails ventricle opening. Thus, additional inclusion of the ventricles in the radiation therapy target volume after ventricle opening does not seem to be indicated. PMID- 26830091 TI - Long-term exposure to irinotecan reduces cell migration in glioma cells. AB - In spite of considerable research into the therapies for glioblastoma multiforme this tumour type remains very difficult to treat. As well as having a tendency to be inherently resistant to chemotherapy, glioblastoma multiforme also displays local invasion. Cell line studies have a continued and important role to play in understanding the mechanisms associated with both chemotherapy resistance and invasion. In the current study we have utilized the C6 glioma cell line to investigate the response to long-term, clinically relevant application of topoisomerase I and II inhibitors. Treatment with etoposide resulted in an increase in resistance to this topoisomerase II inhibitor. By contrast, the continuous exposure to a topoisomerase I inhibitor did not result in increased drug resistance, but was associated with a reduction in cell migration. This data supports further investigation of topoisomerase I inhibition as a means to inhibit glioma invasion without the development of parallel chemoresistance. PMID- 26830092 TI - Cognitive screening in patients with intracranial tumors: validation of the BCSE. AB - This study presents the first validation of the Brief Cognitive Status Exam (BCSE) against two other screening tools for cognitive impairment in patients with intracranial tumors. 58 patients and 22 matched healthy controls completed the BCSE, the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Patients were additionally tested with a comprehensive neuropsychological battery. Based on this assessment, they were classified as cognitively impaired or unimpaired on five cognitive domains. Analyses revealed a comparable feasibility of the BCSE relative to the MoCA and the MMSE, but a smaller range of assessed functions (e.g., no correlation with the domain visual spatial functions). The ability to separate patients and healthy controls was extremely poor for BCSE and MMSE (sensitivity of 38.6 % and less), but moderate for MoCA (sensitivity 68.97 %). Detection of cognitive impairment in patients was worst with BCSE (sensitivity 37 %; MoCA 92.9 %, MMSE 44.4 %) as compared to neuropsychological testing. Moreover, prediction of cognitive outcome was also worst for the BCSE (AUC = .713, NPV = 50 %). An optimal cut-off of 50.5 increased the results slightly. In summary, the BCSE showed good feasibility but no sufficient results in separating healthy individuals from patients or detecting cognitive impairment in patients. Consequently, as a screening measure, we would recommend the MoCA instead of the BCSE. However, since even the MoCA failed to detect cognitive impairment, our study supports the view that reliable results could only be obtained with a comprehensive neuropsychological battery. PMID- 26830093 TI - Valproic acid, compared to other antiepileptic drugs, is associated with improved overall and progression-free survival in glioblastoma but worse outcome in grade II/III gliomas treated with temozolomide. AB - Valproic acid (VPA) is an anti-epileptic drug with properties of a histone deacetylase inhibitor (HDACi). HDACi play a key role in epigenetic regulation of gene expression and have been increasingly used as anticancer agents. Recent studies suggest that VPA is associated with improved survival in high-grade gliomas. However, effects on lower grade gliomas have not been examined. This study investigates whether use of VPA correlates with tumor grade, histological progression, progression-free and overall survival (OS) in grade II, III, and IV glioma patients. Data from 359 glioma patients (WHO II-IV) treated with temozolomide plus an antiepileptic drug (VPA or another antiepileptic drug) between January 1997 and June 2013 at the Massachusetts General Hospital was analyzed retrospectively. After confounder adjustment, VPA was associated with a 28 % decrease in hazard of death (p = 0.031) and a 28 % decrease in the hazard of progression or death (p = 0.015) in glioblastoma. Additionally, VPA dose correlated with reduced hazard of death by 7 % (p = 0.002) and reduced hazard of progression or death by 5 % (p < 0.001) with each 100 g increase in total dose. Conversely, in grade II and III gliomas VPA was associated with a 118 % increased risk of tumor progression or death (p = 0.014), and every additional 100 g of VPA raised the hazard of progression or death by 4 %, although not statistically significant (p = 0.064). Moreover, grade II and III glioma patients taking VPA had 2.17 times the risk of histological progression (p = 0.020), although this effect was no longer significant after confounder adjustment. In conclusion, VPA was associated with improved survival in glioblastoma in a dose-dependent manner. However, in grade II and III gliomas, VPA was linked to histological progression and decrease in progression-free survival. Prospective evaluation of VPA treatment for glioma patients is warranted to confirm these findings. PMID- 26830094 TI - Production of a therapeutic protein by fusing it with two fragments of the carboxyl-terminal peptide of human chorionic gonadotropin beta-subunit in Pichia pastoris. AB - OBJECTIVE: To produce a therapeutic protein (endostatin) by fusion with two fragments of the carboxyl-terminal peptide (CTP) of the human chorionic gonadotropin beta-subunit in Pichia pastoris. RESULTS: Two CTP sequences were fused to the C-terminal of human endostatin, and the fusion protein (endo-CTP) was expressed by P. pastoris. Endo-CTP inhibited proliferation of endothelial cells with an IC50 of 7 MUg ml(-1), and 30 % of cells were annexin V-positive after treatment with 20 MUg endo-CTP ml(-1) for 48 h. Migration of endothelial cells was inhibited by endo-CTP in a concentration-dependent manner. The half life of endo-CTP in Sprague-Dawley rats was much longer than that of its commercial counterpart (Endostar). CONCLUSION: A long-acting endostatin can be produced using CTP technology. PMID- 26830095 TI - Production of an oligosaccharide-specific cellobiohydrolase from the thermophilic fungus Thielavia terrestris. AB - OBJECTIVES: To express and determine the hydrolytic activity of a cellobiohydrolase (TTCBH6B) from the thermophilic fungus Thielavia terrestris in Pichia pastoris. RESULTS: Ttcbh6B encodes a protein of 507 amino acid residues with a predicted molecular mass of 54 kDa. TTCBH6B contains a familial 6-glycosyl hydrolase catalytic domain and a type I carbohydrate-binding module. TTCBH6B was expressed and purified to homogeneity but the purified enzyme was inactive against Avicel. It could, however, digest Celluclast-treated Avicel producing cellobiose (0.27 MUmol min(-1) mg(-1)). To determine the substrate preferences of TTCBH6B, oligosaccharides of varying numbers of subunits were generated by acid hydrolysis of Avicel and fluorescently tagged. Peaks corresponding to oligosaccharides containing three to six glucose units were reduced to cellobiose after addition of TTCBH6B. CONCLUSION: TTCBH6B is active against shorter oligosaccharides rather than polysaccharides. PMID- 26830096 TI - Prognosis of eyelid sebaceous gland carcinoma based on the tumor (T) category of the American Joint Committee on Cancer (AJCC) classification. AB - The purpose of this study was to evaluate the clinical features and prognosis of eyelid sebaceous gland carcinoma (SGC) based on the T category of the American Joint Committee on Cancer (AJCC) classification (7th edition). This is a retrospective interventional case series study. Based on the T category of the AJCC classification, 191 patients with eyelid sebaceous gland carcinoma were classified as T1 (n = 1, 1 %), T2 (n = 111, 58 %), T3 (n = 76, 40 %), and T4 (n = 3, 2 %). Based on multivariate analysis, the factors predictive of regional lymph node metastasis included duration of symptoms >6 months (p = 0.04) and orbital tumor extension (p < 0.001). The factors predictive of systemic metastasis included orbital tumor extension (p < 0.001) and perivascular invasion (p = 0.007). The factor predictive of death due to systemic metastasis included orbital tumor extension (p < 0.001). Kaplan-Meier estimates of regional lymph node metastasis at 5 and 10 years, respectively, were 0 and 0 % for T1, 11 and 11 % for T2, 44 and 59 % for T3, and 100 and 100 % for T4 (p < 0.001). Kaplan-Meier estimates of systemic metastasis at 5 and 10 years, respectively, were 0 and 0 % for T1, 6 and 6 % for T2, 35 and 35 % for T3, and 100 and 100 % for T4 (p < 0.001). Kaplan-Meier estimates of death due to metastasis at 5 and 10 years, respectively, were 0 and 0 % for T1, 3 and 3 % for T2, 30 and 50 % for T3, and 100 and 100 % for T4 (p < 0.001). Primary tumor (T) category of the AJCC classification predicts the prognosis of patients with eyelid SGC. The risk of systemic metastasis and death increases with increasing tumor category. PMID- 26830097 TI - In-hospital outcome of transcatheter vs. surgical aortic valve replacement in patients with aortic valve stenosis: complete dataset of patients treated in 2013 in Germany. AB - BACKGROUND: Transvascular (TV-AVI) or transapical (TA-AVI) aortic valve implantation (TAVI) is a treatment option for patients with aortic stenosis being at high or prohibitive risk for surgical aortic valve implantation (SAVR). Randomized data demonstrated that these subgroups can safely been treated with TAVI. However, a comparison of SAVR and TAVI in intermediate and low-risk patients is missing. Therefore, the aim of the analysis was to compare TAVI and SAVR in all patients who were treated for aortic valve stenosis in Germany throughout 1 year. METHODS: The mandatory quality assurance collects data on the in-hospital outcome from all patients (n = 20,340) undergoing either SAVR or TAVI in Germany. In order to compare the different treatment approaches patients were categorized into four risk groups using the logistic EuroScore I (ES). In hospital mortality and peri- and postprocedural complications were analyzed. RESULTS: The in-hospital mortality did not differ between TV-AVI and SAVR in the low risk group (ES <10 %: TV-AVI 2.4 %, SAVR 2.0 %, p = 0.302) and was significantly higher for SAVR in all other risk groups (ES 10-20 %: TV-AVI 3.5 %, SAVR 5.3 %; p = 0.025; ES 20-30 %: TV-AVI 5.5 %, SAVR 12.2 %, p < 0.001; ES >30 %: TV-AVI 6.5 %, SAVR 12.9 %, p = 0.008). TA-AVI had a significantly higher mortality in all risk groups compared to TV-AVI. In comparison to SAVR, TA-AVI had a higher mortality in patients with ES <10, comparable mortality in ES 10-20 %, and lower mortality in patients with an ES >20 %. The overall stroke rate was 2.3 %. It occurred more frequently in patients with an ES <10 % treated with a transapical approach (SAVR 1.8 %, TV-AVI 1.9 %, TA-AVI 3.1 %, p < 0.01). There were no statistically significant differences in all other comparisons. CONCLUSIONS: This study demonstrates that TAVI provides excellent outcomes in all risk categories. Compared with SAVR, TV-TAVI yields similar in-hospital mortality among low-risk patients and lower in-hospital mortality among intermediate and high-risk patient populations. PMID- 26830099 TI - An update on polysaccharide-based nanomaterials for antimicrobial applications. AB - Scientific community has made a lot of efforts to combat the infectious diseases using antimicrobial agents, but these are associated with problems of development of multi-drug resistance and their adverse side effects. To tackle these challenges, nanocarrier-based drug delivery system using polysaccharides has received enormous attention in the past few years. These antimicrobial agents can become more efficacious when adsorbed, entrapped, or linked to polysaccharides. In addition, these nanocarrier-based systems provide an increase in the surface area of the drug and are able to achieve the targeted drug delivery as well as used for the synthesis of packaging materials with improved mechanical strength, barrier, and antimicrobial properties. This review focuses on potential therapeutic applications of nanocarrier-based drug delivery systems using polysaccharides for antimicrobial applications. PMID- 26830098 TI - Influence of exercise training on proangiogenic TIE-2 monocytes and circulating angiogenic cells in patients with peripheral arterial disease. AB - BACKGROUND: Inflammation is the driving force in atherosclerosis. One central strategy in the treatment of peripheral arterial disease (PAD) is the promotion of angiogenesis. Here, proangiogenic Tie-2 expressing monocytes (TEM) and circulating angiogenic cells (CAC) play a crucial role. Exercise training (ET) is recommended in PAD patients at Fontaine stage II to promote angiogenesis. METHODS: 40 patients with intermittend claudication (IC) [2 groups: supervised ET (SET) vs. non-supervised ET (nSET), each n = 20] and 20 healthy controls were included in the study. Analysis of TEM and CAC was performed from whole blood by flow-cytometry. TEM were identified via CD45, CD86, CD14, CD16 and analysed for the expression of Tie-2. CAC were identified via their expression of CD45 (CD45dim), CD34 and VEGF-R2 (CD309/KDR). Follow up was performed after mean of 7.65 +/- 1.62 months. RESULTS: In comparison to healthy controls, we found increased proportions of CAC (p < 0.0001) and similar TEM numbers in both ET groups. At follow-up (FU) TEM poroportions increased (p < 0.001) and CAC proportions decreased (p < 0.01), but both more significantly in SET (p < 0.001) than nSET (p = 0.01). Only in SET fibrinogen levels decreased and VEGF-A increased (both p < 0.05). Finally, we found in both ET groups a significant increase in absolute walking distance but with a higher individual increase in SET (p < 0.01). TEM and CAC proportions correlated inversely with the absolute walking distance (CAC: r = -0.296, p = 0.02; TEM: r = -0.270, p = 0.04) as well as with ABI (CAC: r = -0.394, p < 0.01; TEM: r = -0.382, p < 0.01). CONCLUSIONS: ET influences the distribution of CAC and TEM proportions. nSET, although still effective in regard to an improved walking distance, is less effective in the influence of proangiogenic cells and inflammatory burden than SET. Our results indicate SET to be a more preferential exercise form, supporting the necessity to establish more SET programs. PMID- 26830100 TI - 2,3-Butanediol production from cellobiose using exogenous beta-glucosidase expressing Bacillus subtilis. AB - We engineered efficient 2,3-butanediol (23BD) production from cellobiose using Bacillus subtilis. First, we found that B. subtilis harboring an empty vector could produce 23BD from cellobiose. However, productivity using cellobiose as a carbon source was lower than that when using glucose. This lower productivity was improved by adding purified beta-glucosidase from Thermobifida fusca YX (Tfu_0937) in the fermentation. Encouraged by these findings, we found that hydrolysis of cellobiose to glucose was an important reaction of 23BD biosynthesis in B. subtilis using cellobiose. Hence, we created efficient 23BD production from cellobiose using exogenous Tfu_0937-expressing B. subtilis. Using the engineered strain, 21.2 g L(-1) of 23BD was produced after 72 h of cultivation. The productivity and yield were 0.294 g L(-1) h(-1) and 0.35 g 23BD/g cellobiose, respectively. We successfully demonstrated efficient 23BD production from cellobiose by using BGL-expressing B. subtilis. PMID- 26830101 TI - Enhanced butanol production by increasing NADH and ATP levels in Clostridium beijerinckii NCIMB 8052 by insertional inactivation of Cbei_4110. AB - Clostridium beijerinckii is identified as a promising Clostridium strain for industrialization of acetone and butanol (AB) fermentation. It has been reported that high reducing power levels are associated with high butanol yield. In this study, we regulated reducing power by blocking NAD(P)H consumption in C. beijerinckii NCIMB 8052. Gene Cbei_4110, encoding NADH-quinone oxidoreductase (nuoG), is a subunit of the electron transport chain complex I. After inactivation of gene Cbei_4110, the generated mutant strain exhibited a remarkable increase in glucose utilization ratio and enhanced butanol production to 9.5 g/L in P2 medium containing 30 g/L of glucose. NAD(P)H and ATP levels were also increased by one to two times and three to five times, respectively. Furthermore, a comparative transcriptome analysis was carried out in order to determine the mechanism involved in the enhanced activity of the Cbei_4110 inactivated mutant strain. This strategy may be extended for making industrial bio-butanol more economically attractive. PMID- 26830102 TI - Effects of multiple inhibitory components on anaerobic treatment processes in municipal solid waste incineration leachate. AB - This study served to investigate the comparative and combined effects of calcium, ammonia nitrogen, and aquatic humic substances (AHS) on specific methanogenic activity (SMA) in municipal solid waste leachate at mesophilic conditions. Using orthogonal experiments, anaerobic granular sludge was cultured with different concentrations combinations of the three added components for 13 days. The combination of 6000 mg/L calcium, 400 mg/L ammonia nitrogen, and 4000 mg/L AHS was the most inhibitory combination on the SMA of granular sludge, with a calculated 4.49 mL (standard temperature and atmospheric pressure) (STP) CH4/(gVSS.d) of SMA. The SMA with the addition of the inhibitory components was much lower than the control group's (1000 mg/L calcium, 200 mg/L ammonia nitrogen and 2000 mg/L AHS) with a calculated 12.97 mL (STP) CH4/(gVSS.d) of SMA. Calcium was the major inhibitor among the three components followed by AHS. High concentrations of calcium significantly inhibited the utilization of propionate and butyrate in the substrate and further affected the methanogenic process. PMID- 26830103 TI - Microbial degradation of fluorinated drugs: biochemical pathways, impacts on the environment and potential applications. AB - Since the discovery over 60 years ago of fluorocortisone's biological properties (9-alpha-Fluoro derivatives of cortisone and hydrocortisone; Fried J and Sabo EF, J Am Chem Soc 76: 1455-1456, 1954), the number of fluorinated drugs has steadily increased. With the improvement in synthetic methodologies, this trend is likely to continue and will lead to the introduction of new fluorinated substituents into pharmaceutical compounds. Although the biotransformation of organofluorine compounds by microorganisms has been well studied, specific investigations on fluorinated drugs are relatively few, despite the increase in the number and variety of fluorinated drugs that are available. The strength of the carbon fluorine bond conveys stability to fluorinated drugs; thus, they are likely to be recalcitrant in the environment or may be partially metabolized to a more toxic metabolite. This review examines the research done on microbial biotransformation and biodegradation of fluorinated drugs and highlights the importance of understanding how microorganisms interact with this class of compound from environmental, clinical and biotechnological perspectives. PMID- 26830104 TI - Development of SCAR markers for rapid and specific detection of Pseudomonas syringae pv. morsprunorum races 1 and 2, using conventional and real-time PCR. AB - Specific primers were developed to detect the causal agent of stone fruit bacterial canker using conventional and real-time polymerase chain reaction (PCR) methods. PCR melting profile (PCR MP) used for analysis of diversity of Pseudomonas syringae strains, allowed to pinpoint the amplified fragments specific for P. syringae pv. morsprunorum race 1 (Psm1) and race 2 (Psm2), which were sequenced. Using obtained data, specific sequence characterised amplified region (SCAR) primers were designed. Conventional and real-time PCRs, using genomic DNA isolated from different bacterial strains belonging to the Pseudomonas genus, confirmed the specificity of selected primers. Additionally, the specificity of the selected DNA regions for Psm1 and Psm2 was confirmed by dot blot hybridisation. Conventional and real-time PCR assays enabled accurate detection of Psm1 and Psm2 in pure cultures and in plant material. For conventional PCR, the detection limits were the order of magnitude ~10(0) cfu/reaction for Psm1 and 10(1) cfu/reaction for Psm2 in pure cultures, while in plant material were 10(0)-10(1) cfu/reaction using primers for Psm1 and 3 * 10(2) cfu/reaction using primers for Psm2. Real-time PCR assays with SYBR Green I showed a higher limit of detection (LOD) - 10(0) cfu/reaction in both pure culture and in plant material for each primer pairs designed, which corresponds to 30-100 and 10-50 fg of DNA of Psm1 and Psm2, respectively. To our knowledge, this is the first PCR-based method for detection of the causal agents of bacterial canker of stone fruit trees. PMID- 26830105 TI - CHADS2 score predicts risk of contrast-induced nephropathy in stable coronary artery disease patients undergoing percutaneous coronary interventions. AB - BACKGROUND/PURPOSE: To investigate the correlation between the CHADS2 score and risk of contrast-induced nephropathy (CIN), we conducted a retrospective study in patients who underwent elective percutaneous coronary intervention (PCI) and compared its accuracy with previous scoring systems. METHODS: A total of 539 patients who underwent elective PCI were enrolled. Based on their underlying diseases, such as hypertension, diabetes, and kidney disease, CHADS2 score, R2CHADS2 score, and Mehran's risk score were calculated for each patient. Incidence of CIN was defined as a rise in serum creatinine >0.5 mg/dL or >25% increase in baseline within 48 hours after PCI. All study participants were followed up until October 2014, or until the occurrence of major adverse cardiovascular events (MACEs). RESULTS: Overall, 55 cases (10.2%) of CIN and 90 cases (16.7%) of MACEs were identified after participants were followed up for 1.57 +/- 1.46 years. The study cohort was divided into three groups according to CHADS2 scores: score 0, score 1-2, and score 3-6. In multivariate analysis, an increase of 1 point in the CHADS2 score was independently associated with a 37% increase in the risk of CIN (odds ratio, 1.37; 95% confidence interval, 1.00 1.87; p = 0.048) and a 49% increase in MACEs (hazard ratio, 1.49; 95% confidence interval, 1.18-1.88, p = 0.001). In pairwise comparison, the discriminatory performance of CHADS2 score was not inferior to either R2CHADS2 score (p = 0.226) or Mehran's risk score (p = 0.075). CONCLUSION: CHADS2 score could be a simple and useful predictor for CIN in patients undergoing elective PCI. PMID- 26830106 TI - [Centralized biobanks: a basis for medical research]. AB - Biobanks are the basis for a substantial part of biomedical research. The development, establishment and operation of biobanks are connected to a broad range of aspects, mainly concerning the preparation, storage, usage and dissemination of samples and associated data, in addition to the social and public involvement of these processes. These complex requirements can often only be managed in large centralized biobanks. In recent years, centralized clinical biobanks have been established in several university clinics in Germany. Similar activities take place in other European countries and worldwide. This article highlights the requirements and main tasks of centralized clinical biobanks: high quality pre-analytics and sample storage, the creation of professional IT structures, data protection, ethical issues, in addition to quality and project management. PMID- 26830107 TI - Restriction of pelvic lateral and rotational motions alters lower limb kinematics and muscle activation pattern during over-ground walking. AB - Restriction of pelvic lateral and rotational motions caused by robotic gait assistive devices can hinder satisfactory functional outcomes as it alters normal gait patterns. However, the effect of pelvic motion restriction caused by assistive devices on human locomotion is still unclear; thus, we empirically evaluated the influences of pelvic lateral and rotational motions on gait during over-ground walking by inhibiting the respective pelvic motions. The pelvic motions were restricted through a newly developed over-ground walking device. Variations in gait descriptive parameters as well as joint kinematics and muscle activation patterns were measured to indicate gait difference caused by pelvic restrictions. The results showed that pelvic lateral and rotational restriction significantly reduced the stride and step length as well as gait velocity and increased ratio of stance phase. It was also observed that the restriction caused a significant reduction in the range of motion of the ankle, knee, and hip joints. In addition, significantly higher muscle activations and prolonged patterns were observed in the tibialis anterior, gastrocnemius, and biceps femoris muscles, as compared to the normal patterns when the pelvis was restricted. We concluded that the pelvic restriction significantly altered normal gait dynamics, thus inhibiting the efficacy of gait rehabilitation. PMID- 26830108 TI - Towards understanding microvillus inclusion disease. AB - Microvillus inclusion disease (MVID) is characterised by onset of intractable life-threatening watery diarrhoea during infancy. Transmission electron microscopy demonstrates shortening or absence of apical microvilli, pathognomonic microvillus inclusions in mature enterocytes and subapical accumulation of periodic acid-Schiff-positive granules or vesicles confirming diagnosis. Mutations in MYO5B have been found to cause MVID. In two patients with MVID, whole-exome sequencing of DNA revealed homozygous truncating mutations in STX3. Mutations in these genes disrupt trafficking between apical cargo vesicles and the apical plasma membrane. Thus, disturbed delivery of certain brush border membrane proteins is a common defect in MVID. PMID- 26830109 TI - Milk glucosidase activity enables suckled pup starch digestion. AB - ?: Starch requires six enzymes for digestion to free glucose: two amylases (salivary and pancreatic) and four mucosal maltase activities; sucrase-isomaltase and maltase-glucoamylase. All are deficient in suckling rodents. OBJECTIVE: The objective of this study is to test (13)C-starch digestion before weaning by measuring enrichment of blood (13)C-glucose in maltase-glucoamylase-null and wild type mice. METHODS: Maltase-glucoamylase gene was ablated at the N-terminal. Dams were fed low (13)C-diet and litters kept on low (13)C-diet. Pups were weaned at 21 days. Digestion was tested at 13 and 25 days by intragastric feeding of amylase predigested (13)C-alpha-limit dextrins. Blood (13)C-glucose enrichment was measured by gas chromatography combustion isotope ratio mass spectrometry (GCRMS) using penta-acetate derivatives. RESULTS: Four hours after feeding, blood (13)C-glucose was enriched by 26 * 10(3) in null and 18 * 10(3) in wild-type mice at 13 days and 0.3 * 10(3) and 0.2 * 103 at 25 days (vs. fasting p = 0.045 and p = 0.045). By jejunal enzyme assay, immunohistochemistry, or Western blots, there was no maltase activity or brush border staining with maltase-glucoamylase antibodies at 13 days, but these were fully developed in the wild-type mice by 25 days. In 13-day null mice, luminal contents were stained by maltase-glucoamylase antibodies. Lactating the mammary gland revealed maltase-glucoamylase antibody staining of alveolar cells. Reverse transcription/polymerase chain reaction (RT/PCR) of lactating glands revealed a secreted form of maltase-glucoamylase. CONCLUSIONS: (1) (13)C-alpha-limit dextrins were rapidly digested to (13)C glucose in 13-day mice independent of maltase-glucoamylase genotype or mucosal maltase activity. (2) This experiment demonstrates that a soluble maltase activity is secreted in mouse mother's milk which enables suckling pup starch digestion well before brush border enzyme development. (3) This experiment with (13)C-alpha-limit dextrins needs to be repeated in human breast fed infants. PMID- 26830110 TI - Empathy Impairments in Intimate Partner Violence Perpetrators With Antisocial and Borderline Traits: A Key Factor in the Risk of Recidivism. AB - Antisocial, borderline, and narcissistic personality traits have been described as characteristics of intimate partner violence (IPV) perpetrators. Furthermore, deficits in cognitive empathy and impairments in emotional decoding processes may at least partially explain conduct disorders and social dysfunction in general. However, previous research has not explored potential associations between empathy deficits and the aforementioned traits or whether they are reflected in recidivism in IPV perpetrators. Accordingly, the main aim of this study was to explore associations between empathy deficits, antisocial, borderline, and narcissistic traits and the risk of recidivism in this population. The sample consisted of 144 IPV perpetrators (mean age = 41 years). High antisocial and borderline personality traits in this sample were associated with a high risk of recidivism, these relationships being moderated by poor empathy skills. Moreover, in IPV perpetrators with both antisocial and borderline personality traits, the risk of recidivism was higher than in those with only one of these traits. In contrast, narcissistic traits were unrelated to the risk of recidivism and impairments in empathy. The results of our study highlight the importance of empathy deficits and may help professionals to develop specific intervention programs focusing on improving empathy skills in antisocial and borderline IPV perpetrators. PMID- 26830111 TI - Trajectories of ADHD severity over 10 years from childhood into adulthood. AB - The study examined unique trajectories of ADHD severity from childhood (7-16 yo at baseline) through adulthood in a sample of ADHD, bipolar and healthy subjects. Comorbid disorders and temperament were examined as correlates of course of ADHD. N = 81 participants with an ADHD diagnosis, ascertained as a comparison group in a study of bipolar disorder (BP-I), were followed over a 10-year period. Growth mixture modeling (GMM) of ADHD severity was used to investigate trajectories of ADHD severity over 10 years. GMM revealed four trajectories in the N = 251 participants included in these analyses. A persisting high ADHD trajectory had the highest rates of comorbid major depressive disorder and oppositional defiant disorder. This persisting high ADHD group also had higher fantasy and lower persistence and self-directedness compared with those who displayed a pattern of decreasing ADHD symptoms over time. Psychopathologic features that characterize divergent trajectories of ADHD into adulthood are elucidated, and additional, larger studies are warranted. PMID- 26830112 TI - An observational study of adult admissions to a medical ICU due to adverse drug events. AB - BACKGROUND: The objectives of the study were to estimate the incidence of intensive care unit (ICU) admissions due to adverse drug events (ADEs), to assess preventability, severity and costs of the corresponding ADE and to determine the leading causes of preventable ADEs. METHODS: An observational study was conducted in a medical ICU of a teaching hospital from February 2013 to February 2014. RESULTS: A total of 743 consecutive admissions were included, and they involved 701 different patients. The included admissions were categorized into three groups (admissions due to preventable ADE, admissions due to unpreventable ADE and the control group). Among the 743 ICU admissions included during the study period, 173 (23.3 %) were due to ADE, with 102 (13.7 %) related to preventable ADE and 71 (9.6 %) to unpreventable ADE, yielding a preventability rate of ADE of 0.59 (102/173). Admissions due to unpreventable ADE concerned patients with more comorbidities, a greater number of drugs and higher Simplified Acute Physiology Score II than admissions due to preventable ADE and the control group admissions (n = 570). Hospital mortality rates, corresponding costs and length of stay were all similar in the preventable ADE and control groups, whereas they were always significantly higher in the unpreventable ADE group. ICU mortality, length of stay and the corresponding costs were similar in the three groups. Non-compliance was the principal leading cause of preventable ADE (n = 31/102). The 102 preventable ADE-related admissions accounted for a total of 528 days of hospitalization in the ICU, requiring a mean of 1.4 ICU beds per day over the one year period, with an associated total cost amounting to 747,651 ?. CONCLUSIONS: ADE was a major cause of admission in the studied ICU, and in 59 % of the cases, ADEs were preventable. The reported burden of ICU admissions due to ADE advocates for further investigations to explore how the rate of such admissions could be decreased. PMID- 26830114 TI - Thymic stromal lymphopoietin and IL-33 promote skin inflammation and vaccinia virus replication in a mouse model of atopic dermatitis. PMID- 26830113 TI - Rett Syndrome: Crossing the Threshold to Clinical Translation. AB - Lying at the intersection between neurobiology and epigenetics, Rett syndrome (RTT) has garnered intense interest in recent years, not only from a broad range of academic scientists, but also from the pharmaceutical and biotechnology industries. In addition to the critical need for treatments for this devastating disorder, optimism for developing RTT treatments derives from a unique convergence of factors, including a known monogenic cause, reversibility of symptoms in preclinical models, a strong clinical research infrastructure highlighted by an NIH-funded natural history study and well-established clinics with significant patient populations. Here, we review recent advances in understanding the biology of RTT, particularly promising preclinical findings, lessons from past clinical trials, and critical elements of trial design for rare disorders. PMID- 26830115 TI - Variants near the HLA complex group 22 gene (HCG22) confer increased susceptibility to late-onset asthma in Japanese populations. PMID- 26830117 TI - The (kinetic) theory of active particles applied to learning dynamics: Comment on "Collective learning modeling based on the kinetic theory of active particles" by D. Burini et al. PMID- 26830116 TI - Filaggrin genotype does not determine the skin's threshold to UV-induced erythema. PMID- 26830118 TI - Phonology in the mirror: Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael A. Arbib. PMID- 26830119 TI - Information on living systems: A kinetic approach: Comment on the paper "Collective learning modeling based on the kinetic theory of active particles" by D. Burini et al. PMID- 26830120 TI - Surgical approaches to intramedullary nailing of the tibia: Comparative analysis of knee pain and functional outcomes. AB - INTRODUCTION: Post-operative knee pain is common following intramedullary nailing of the tibia, regardless of surgical approach, though the exact source is controversial. Historically, the most common surgical approaches position the knee in hyperflexion, including patellar tendon splitting (PTS) and medial parapatellar (MPP). A novel technique, the semi-extended lateral parapatellar approach simplifies patient positioning, fracture reduction, fluoroscopic assessment, and implant insertion. It also avoids violation of the knee joint capsule. However, this approach has not yet been directly compared against the historical standards. We hypothesised that in a comparison of patient outcomes, the semi-extended approach would be associated with decreased knee pain and better function relative to knee hyperflexion approaches. METHODS: A trauma patient database from a Level I centre was queried for patients who underwent intramedullary nailing of the tibia between 2009 and 2013. Patients were surveyed for knee pain severity (NRS scale 1 to 10) and location, and completion of the Lysholm Knee Scale (LKS). Data was compared between the semi-extended lateral parapatellar, medial parapatellar, and tendon splitting groups regarding knee pain severity, location, total LKS, and individual knee function scores from the Lysholm questionnaire. Pre-hoc power analysis determined the necessary sample size (n=34). Post-hoc analysis utilised two-way ANOVA analysis with a significance threshold of p<0.05. RESULTS: Comparison of knee pain severity between the groups found no significant difference (p=0.69), with average ratings of: semi-extended (3.26), PTS (3.59), and MPP (3.63). Analysis found no significant differences in total LKS score (p=0.33), with average sums of: semi extended (75.97), MPP (77.53), and PTS (81.68). Individual knee function scores from the LKS were similar between the groups, except for limping, with MPP being significantly worse (p=0.04). There was no significant difference in knee pain location (p=0.45). CONCLUSION: In this adequately-powered study, at minimum 1 year follow-up there were no significant differences between the 3 approaches in knee pain severity, location, or overall function. The three were significantly different in post-operative limping, with medial parapatellar having the lowest score. The semi-extended lateral parapatellar approach vastly simplifies many technical aspects of nailing compared to knee hyperflexion approaches, and does not violate the knee joint. PMID- 26830121 TI - Prehospital use of hemostatic dressings in emergency medical services in the Netherlands: A prospective study of 66 cases. AB - BACKGROUND: Uncontrolled haemorrhage is the leading cause of potentially preventable death in both civilian and military trauma patients. Animal studies and several case series have shown that hemostatic dressings reduce haemorrhage and might improve survival. One of these products is HemCon ChitoGauze((r)). The objective of this study was to determine the effectiveness and safety of ChitoGauze in achieving hemostasis in massive traumatic bleeding in civilian emergency medical services. METHODS: From June 2012 to December 2014, all ambulances of two emergency medical services in the Netherlands were equipped with ChitoGauze. The dressing was used according to protocol; if conventional treatment (gauze dressing with manual pressure) failed to control external traumatic bleeding or if conventional treatment was unlikely to achieve hemostasis. The ambulance personnel filled in an evaluation form after each use. RESULTS: A total of 66 patients were treated with ChitoGauze during the study period. Twenty-one patients were taking anticoagulants or suffered from a clotting disorder. The injuries were located in the extremities (n=29), the head and face (n=29), or the neck, thorax and groin (n=8). In 46/66 patients, the use of ChitoGauze resulted in cessation of haemorrhage. In 13/66 patients, Chitogauze application reduced haemorrhage. ChitoGauze failed to control haemorrhage in 7/66 patients, whereby user error was a contributing factor in 3 of these failures. No side effects have been observed during treatment or transport of the patients and no adverse effects have been reported in discharge letters. CONCLUSION: This is the largest prospective study in civilian healthcare and the second largest case series with prehospital use of hemostatic dressings. It demonstrated that ChitoGauze is an effective and safe adjunct in the prehospital treatment of massive external traumatic haemorrhage. PMID- 26830122 TI - The prevalence of alcohol-related trauma recidivism: A systematic review. AB - OBJECTIVE: Recurrent admission to a hospital or trauma centre for separate incidents of traumatic injury is known as trauma recidivism. Although use of alcohol is a known risk factor for injury and associated with trauma recidivism, the scale of alcohol-related trauma recidivism has not been well described. The purpose of this review was to search the published literature for studies that evaluated the prevalence of alcohol use among trauma recidivists. Our primary objective was to determine the proportion of trauma recidivism related to alcohol use. The association between alcohol and trauma recidivism was evaluated as a secondary objective. METHODS: Four electronic databases (MEDLINE, Embase, CINAHL, Web of Science) were searched from inception until December 2015 for all articles that might provide evidence on the proportion of trauma recidivism related to use of alcohol. After removal of duplicates, the search strategy yielded 2470 records for screening. Only primary studies that reported on repeated admissions to a hospital or trauma centre for traumatic injuries specifically related to alcohol use were included. Descriptive statistics were used to assess study characteristics and the prevalence of trauma recidivism related to alcohol use. An aggregate weighted estimate of alcohol-related trauma recidivism was calculated. RESULTS: A total of 12 studies met all inclusion criteria. Studies were published between 1989 and 2014. Overall, there were 3386 trauma recidivists among included studies. The proportion of trauma recidivists with evidence of alcohol use on admission ranged from 26.7% to 76.9% (median 46.4%). The aggregated sample produced a weighted estimate of 41.0% (1388/3386) for alcohol related trauma recidivism. In four studies, the association between alcohol and trauma recidivism was examined; all four found a positive association between alcohol use and repeated admission for traumatic injury. Studies varied considerably in design, trauma populations, periods for evaluating recidivism, definitions for positive alcohol on admission, and methods used to determine alcohol use. CONCLUSION: Evidence from current literature suggests that 41.0% of trauma recidivism is related to use of alcohol. Due to methodological limitations among the studies included for review, this may underestimate the actual prevalence of alcohol-related trauma recidivism. PMID- 26830123 TI - Treating patients with diabetes and cardiovascular disease--Does the glucose matter? PMID- 26830124 TI - Evidence that ubiquitylated H2B corrals hDot1L on the nucleosomal surface to induce H3K79 methylation. AB - Ubiquitylation of histone H2B at lysine 120 (H2B-Ub), a post-translational modification first discovered in 1980, plays a critical role in diverse nuclear processes including the regulation of transcription and DNA damage repair. Herein, we use a suite of protein chemistry methods to explore how H2B-Ub stimulates hDot1L-mediated methylation of histone H3 on lysine 79 (H3K79me). By using semisynthetic 'designer' chromatin containing H2B-Ub bearing a site specifically installed photocrosslinker, here we report an interaction between a functional hotspot on ubiquitin and the N-terminus of histone H2A. Our biochemical studies indicate that this interaction is required for stimulation of hDot1L activity and leads to a repositioning of hDot1L on the nucleosomal surface, which likely places the active site of the enzyme proximal to H3K79. Collectively, our data converge on a possible mechanism for hDot1L stimulation in which H2B-Ub physically 'corrals' the enzyme into a productive binding orientation. PMID- 26830125 TI - The limits of precision monomer placement in chain growth polymerization. AB - Precise control over the location of monomers in a polymer chain has been described as the 'Holy Grail' of polymer synthesis. Controlled chain growth polymerization techniques have brought this goal closer, allowing the preparation of multiblock copolymers with ordered sequences of functional monomers. Such structures have promising applications ranging from medicine to materials engineering. Here we show, however, that the statistical nature of chain growth polymerization places strong limits on the control that can be obtained. We demonstrate that monomer locations are distributed according to surprisingly simple laws related to the Poisson or beta distributions. The degree of control is quantified in terms of the yield of the desired structure and the standard deviation of the appropriate distribution, allowing comparison between different synthetic techniques. This analysis establishes experimental requirements for the design of polymeric chains with controlled sequence of functionalities, which balance precise control of structure with simplicity of synthesis. PMID- 26830126 TI - 40 years of terrorist bombings - A meta-analysis of the casualty and injury profile. AB - INTRODUCTION: Terrorists have used the explosive device successfully globally, with their effects extending beyond the resulting injuries. Suicide bombings, in particular, are being increasingly deployed due to the devastating effect of a combination of high lethality and target accuracy. The aim of this study was to identify trends and analyse the demographics and casualty figures of terrorist bombings worldwide. METHODS: Analysis of the Global Terrorism Database (GTD) and a PubMed/Embase literature search (keywords "terrorist", and/or "suicide", and/or "bombing") from 1970 to 2014 was performed. RESULTS: 58,095 terrorist explosions worldwide were identified in the GTD. 5.08% were suicide bombings. Incidents per year are increasing (P<0.01). Mean casualty statistics per incidents was 1.14 deaths and 3.45 wounded from non-suicide incidents, and 10.16 and 24.16 from suicide bombings (p<0.05). The kill:wounded ratio was statistically higher in suicide attacks than non-suicide attacks, 1:1.3 and 1:1.24 respectively (p<0.05). The Middle East witnessed the most incidents (26.9%), with Europe (13.2%) ranked 4th. The literature search identified 41 publications reporting 167 incidents of which 3.9% detailed building collapse (BC), 60.8% confined space (CS), 23.5% open space (OS) and 11.8% semi-confined space (SC) attacks. 60.4% reported on suicide terrorist attacks. Overall 32 deaths and 180 injuries per incident were seen, however significantly more deaths occurred in explosions associated with a BC. Comparing OS and CS no difference in the deaths per incident was seen, 14.2(SD+/ 17.828) and 15.63 (SD+/-10.071) respectively. However OS explosions resulted in significantly more injuries, 192.7 (SD+/-141.147), compared to CS, 79.20 (SD+/ 59.8). Extremity related wounds were the commonest injuries seen (32%). DISCUSSION/CONCLUSION: Terrorist bombings continue to be a threat and are increasing particularly in the Middle East. Initial reports, generated immediately at the scene by experienced coordination, on the type of detonation (suicide versus non-suicide), the environment of detonation (confined, open, building collapse) and the number of fatalities, and utilising the Kill:Wounded ratios found in this meta-analysis, can be used to predict the number of casualties and their likely injury profile of survivors to guide the immediate response by the medical services and the workload in the coming days. PMID- 26830127 TI - Classifying, measuring and improving the quality of data in trauma registries: A review of the literature. AB - INTRODUCTION: Globally, injury is a major cause of death and disability. Improvements in trauma care have been driven by trauma registries. The capacity of a trauma registry to inform improvements in the quality of trauma care is dependent upon the quality of data. The literature on data quality in disease registries is inconsistent and ambiguous; methods used for classifying, measuring, and improving data quality are not standardised. The aim of this study was to review the literature to determine the methods used to classify, measure and improve data quality in trauma registries. METHODS: A scoping review of the literature was performed. Databases were searched using the term "trauma registry" and its synonyms, combined with multiple terms denoting data quality. There was no restriction on year. Full-length manuscripts were included if the classification, measurement or improvement of data quality in one or more trauma registries was a study objective. Data were abstracted regarding registry demographics, study design, data quality classification, and the reported methods used to measure and improve the pre-defined data quality dimensions of accuracy, completeness and capture. RESULTS: Sixty-nine publications met the inclusion criteria. Four publications classified data quality. The most frequently described methods for measuring data accuracy (n=47) were checks against other datasets (n=18) and checks of injury coding (n=17). The most frequently described methods for measuring data completeness (n=47) were the percentage of included cases, for a given variable or list of variables, for which there was an observation in the registry (n=29). The most frequently described methods for measuring data capture (n=37) were the percentage of cases in a linked reference dataset that were also captured in the primary dataset being evaluated (n=24). Most publications dealing with the measurement of a dimension of data quality did not specify the methods used; most publications dealing with the improvement of data quality did not specify the dimension being targeted. CONCLUSION: The classification, measurement and improvement of data quality in trauma registries is inconsistent. To maintain confidence in the usefulness of trauma registries, the metrics and reporting of data quality need to be standardised. PMID- 26830128 TI - Titanium and steel fracture fixation plates with different surface topographies: Influence on infection rate in a rabbit fracture model. AB - INTRODUCTION: Implant-related infection is a challenging complication in musculoskeletal trauma surgery. In the present study, we examined the role of implant material and surface topography as influencing factors on the development of infection in an experimental model of plating osteosynthesis in the rabbit. METHODS: The implants included in this experimental study were composed of: standard Electropolished Stainless Steel (EPSS), standard titanium (Ti-S), roughened stainless steel (RSS) and surface polished titanium (Ti-P). Construct stability and load-to-failure of Ti-P implants was compared to that of Ti-S implants in a rabbit cadaveric model. In an in vivo study, a rabbit humeral fracture model was used. Each rabbit received one of three Staphylococcus aureus inocula, aimed at determining the infection rate at a low, medium and high dose of bacteria. Outcome measures were quantification of bacteria on the implant and in the surrounding tissues, and determination of the infectious dose 50 (ID50). RESULTS: No significant differences were observed between Ti-S and Ti-P regarding stiffness or failure load in the cadaver study. Of the 72 rabbits eventually included in the in vivo study, 50 developed an infection. The ID50 was found to be: EPSS 3.89*10(3) colony forming units (CFU); RSS 8.23*10(3) CFU; Ti-S 5.66*10(3) CFU; Ti-P 3.41*10(3) CFU. Significantly lower bacterial counts were found on the Ti-S implants samples compared with RSS implants (p<0.001) at the high inoculum. Similarly, lower bacterial counts were found in the bone samples of animals in the Ti-S group in comparison with both RSS and EPSS groups, again at the high inoculation dose (p<0.005). CONCLUSION: No significant differences were seen in susceptibility to infection when comparing titanium and steel implants with conventional or modified topographies. Ti-P implants, which have previously been shown in preclinical studies to reduce complications associated with tissue adherence, do not affect infection rate in this preclinical fracture model. Therefore, Ti-P implants are not expected to affect the infection rate, or influence implant stability in the clinical situation. PMID- 26830129 TI - Krypton oxides under pressure. AB - Under high pressure, krypton, one of the most inert elements is predicted to become sufficiently reactive to form a new class of krypton compounds; krypton oxides. Using modern ab-initio evolutionary algorithms in combination with Density Functional Theory, we predict the existence of several thermodynamically stable Kr/O species at elevated pressures. In particular, our calculations indicate that at approx. 300 GPa the monoxide, KrO, should form spontaneously and remain thermo- and dynamically stable with respect to constituent elements and higher oxides. The monoxide is predicted to form non-molecular crystals with short Kr-O contacts, typical for genuine chemical bonds. PMID- 26830130 TI - Ventricular myocyte injury by high-intensity electric field: Effect of pulse duration. AB - Although high-intensity electric fields (HEF) application is currently the only effective therapy available to terminate ventricular fibrillation, it may cause injury to cardiac cells. In this study we determined the relation between HEF pulse length and cardiomyocyte lethal injury. We obtained lethality curves by survival analysis, which were used to determine the value of HEF necessary to kill 50% of cells (E50) and plotted a strength-duration (SxD) curve for lethality with 10 different durations: 0.1, 0.2, 0.5, 1, 3, 5, 10, 20, 35 and 70 ms. For the same durations we also obtained an SxD curve for excitation and established an indicator for stimulatory safeness (stimulation safety factor - SSF) as the ratio between the SxD curve for lethality and one for excitation. We found that the lower the pulse duration, the higher the HEF intensity required to cell death. Contrary to expectations, the highest SSF value does not correspond to the lowest pulse duration but to the one of 0.5 ms. As defibrillation threshold has been described as duration-dependent, our results imply that the use of shorter stimulus duration - instead of the one typically used in the clinic (10 ms) - might increase defibrillation safeness. PMID- 26830131 TI - Apoptosis and electroretinogram after intravitreal injection of methotrexate in an experimental rabbit model. AB - The aim of this study was to explore the changes in electroretinogram of rabbit retina and apoptosis in methotrexate-induced toxicity. Rabbits were divided into 5 groups. Group I served as control in which saline solutions was injected intravitreally. Methotrexate (800 MUg, 1.76 MUmol) was injected into the vitreous of both eyes of rabbits groups II, III, IV and V by an insulin injector with a 26 gauge needle under general anesthesia. Retinal function was assessed by electroretinogram (ERG) after 2, 4, 10 days and one month then animals were decapitated. The eyes were enucleated and processed for DNA fragmentation studies by gel electrophoresis to retinae and measurement of caspase-3 activities. The results indicated a significant reduction (p ? 0.05) in a- and b-wave, a time dependent appearance of the typical ladder pattern of internucleosomal fragmentation, a characteristic of apoptosis and increase of relative caspase-3 activity after methotrexate intravitreal injection. Methotrexate lead to apoptosis, increase of caspase-3 and affect retinal function. PMID- 26830132 TI - The cytoprotective effect of isorhamnetin against oxidative stress is mediated by the upregulation of the Nrf2-dependent HO-1 expression in C2C12 myoblasts through scavenging reactive oxygen species and ERK inactivation. AB - This study was designed to confirm the protective effects of isorhamnetin against oxidative stress-induced cellular damage. Our results indicated that isorhamnetin inhibited the hydrogen peroxide (H2O2)-induced growth inhibition and exhibited scavenging activity against the intracellular reactive oxygen species (ROS) in mouse-derived C2C12 myoblasts. Isorhamnetin also significantly attenuated H2O2 induced DNA damage and apoptosis, and increased the levels of the nuclear factor erythroid 2-related factor 2 (Nrf2) and its phosphorylation associated with the induction of heme oxygenase-1 (HO-1). However, the protective effects of isorhamnetin on H2O2-induced ROS and growth inhibition were significantly abolished by an HO-1 competitive inhibitor. Moreover, the potential of isorhamnetin to mediate HO-1 induction and protect against H2O2-mediated growth inhibition was abrogated by transient transfection with Nrf2-specific small interfering RNA. Additionally, isorhamnetin induced the activation of mitogen activated protein kinases (MAPKs), such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. However, the specific inhibitor of ERK, but not JNK and p38 MAPK, was able to abolish the HO-1 upregulation and the Nrf2 phosphorylation. Collectively, these results demonstrate that isorhamnetin augments the cellular antioxidant defense capacity by activating the Nrf2/HO-1 pathway involving the activation of the ERK pathway, thus protecting the C2C12 cells from H2O2-induced cytotoxicity. PMID- 26830133 TI - Myocardial connexin-43 and PKC signalling are involved in adaptation of the heart to irradiation-induced injury: Implication of miR-1 and miR-21. AB - Intercellular connexin-43 (Cx43) channels are essential for electrical coupling and direct cardiac cell to cell communication to ensure heart function. Expression of Cx43 is altered due to stressful conditions and also affected by the alterations in extracellular matrix. We aimed to explore the effect of chest irradiation on myocardial expression of Cx43 and miR-1 which regulates GJA1 gene transcription for Cx43. Implication of miR-21 that regulates expression of extracellular matrix proteins and PKC signalling that may affect Cx43-mediated coupling was examined as well. Western blot and real-time PCR analyses revealed that six weeks after the exposure of healthy Wistar rats chest to single irradiation of 25 Gy significant myocardial alterations were observed: 1)/ increase of total Cx43 protein expression and its functional phosphorylated forms; 2) suppressed levels of miR-1; 3) enhanced expression of PKCepsilon which phosphorylates Cx43; 4) increase of miR-21 levels; 5) increase of PKCdelta expression. These results suggest that irradiation causes post-transcriptional regulation of myocardial Cx43 expression by miR-1 possibly through miR-21 and PKC signalling. We conclude that single dose of irradiation has the potential to enhance myocardial intercellular communication that might be beneficial for the heart that needs to be investigated in details in further studies. PMID- 26830134 TI - Role of acid sphingomyelinase in the age-dependent dysregulation of sphingolipids turnover in the tissues of rats. AB - Old age-associated pathologies usually coincide with altered sphingolipid metabolism. In the present article, the role of acid sphingomyelinase (ASMase) in the age-dependent changes of sphingomyelin (SM) and ceramide contents in the tissues has been investigated by means of ASMase inhibitors, imipramine and zoledronic acid. It has been determined that ceramide content and ceramide/SM ratio increased, while SM level decreased in the heart, liver, blood serum and skeletal muscles of 24-month old rats in contrast to 3-month old animals. Injections of imipramine or zoledronic acid to 24-month old rats resulted in significant downregulation of ASMase in the liver and skeletal and heart muscles. The both inhibitors decreased the ceramide content and ceramide/SM ratio and increased the SM content in all tissues studied, except the heart, of old rats to the levels close to those observed in the young animals. Long-term treatment of rats by inhibitors, which have different mechanisms of action on ASMase, exerts the similar, but not equal effects on enzyme activity and SM turnover. In summary, the data above strongly suggest that the age-dependent up-regulation of ASMase plays an important role in the modulation of ceramide and SM contents in rat tissues and that imipramine and zoledronic acid are useful tools for SM turnover manipulation at old age. PMID- 26830135 TI - Entrapment of soft tissue: a new technique to improve the stability of malar augmentation with hydroxyapatite. PMID- 26830136 TI - Raman-Enhanced Phase-Sensitive Fibre Optical Parametric Amplifier. AB - Phase-sensitive amplification is of great research interest owing to its potential in noiseless amplification. One key feature in a phase-sensitive amplifier is the gain extinction ratio defined as the ratio of the maximum to the minimum gains. It quantifies the capability of the amplifier in performing low noise amplification for high phase-sensitive gain. Considering a phase-sensitive fibre optical parametric amplifier for linear amplification, the gain extinction ratio increases with the phase-insensitive parametric gain achieved from the same pump. In this work, we use backward Raman amplification to increase the phase insensitive parametric gain, which in turn improves the phase-sensitive operation. Using a 955 mW Raman pump, the gain extinction ratio is increased by 9.2 dB. The improvement in the maximum phase-sensitive gain is 18.7 dB. This scheme can significantly boost the performance of phase-sensitive amplification in a spectral range where the parametric pump is not sufficiently strong but broadband Raman amplification is available. PMID- 26830137 TI - Co-expression of truncated and full-length tau induces severe neurotoxicity. AB - Abundant tau inclusions are a defining hallmark of several human neurodegenerative diseases, including Alzheimer's disease. Protein fragmentation is a widely observed event in neurodegenerative proteinopathies. The relevance of tau fragmentation for the neurodegenerative process in tauopathies has yet remained unclear. Here we found that co-expression of truncated and full-length human tau in mice provoked the formation of soluble high-molecular-weight tau, the failure of axonal transport, clumping of mitochondria, disruption of the Golgi apparatus and missorting of synaptic proteins. This was associated with extensive nerve cell dysfunction and severe paralysis by the age of 3 weeks. When the expression of truncated tau was halted, most mice recovered behaviorally and functionally. In contrast, co-expression of full-length tau isoforms did not result in paralysis. Truncated tau thus induces extensive but reversible neurotoxicity in the presence of full-length tau through the formation of nonfilamentous high-molecular-weight tau aggregates, in the absence of tau filaments. Targeting tau fragmentation may provide a novel approach for the treatment of human tauopathies. PMID- 26830138 TI - Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3. AB - The genetic basis of Alzheimer's disease (AD) is complex and heterogeneous. Over 200 highly penetrant pathogenic variants in the genes APP, PSEN1, and PSEN2 cause a subset of early-onset familial AD. On the other hand, susceptibility to late onset forms of AD (LOAD) is indisputably associated to the E4 allele in the gene APOE, and more recently to variants in more than two-dozen additional genes identified in the large-scale genome-wide association studies (GWAS) and meta analyses reports. Taken together however, although the heritability in AD is estimated to be as high as 80%, a large proportion of the underlying genetic factors still remain to be elucidated. In this study, we performed a systematic family-based genome-wide association and meta-analysis on close to 15 million imputed variants from three large collections of AD families (~3500 subjects from 1070 families). Using a multivariate phenotype combining affection status and onset age, meta-analysis of the association results revealed three single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with AD risk: rs7609954 in the gene PTPRG (P-value=3.98 * 10-8), rs1347297 in the gene OSBPL6 (P-value=4.53 * 10-8), and rs1513625 near PDCL3 (P value=4.28 * 10-8). In addition, rs72953347 in OSBPL6 (P-value=6.36 * 10-7) and two SNPs in the gene CDKAL1 showed marginally significant association with LOAD (rs10456232, P-value=4.76 * 10-7; rs62400067, P-value=3.54 * 10-7). In summary, family-based GWAS meta-analysis of imputed SNPs revealed novel genomic variants in (or near) PTPRG, OSBPL6, and PDCL3 that influence risk for AD with genome-wide significance. PMID- 26830139 TI - Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1. AB - Caloric restriction (CR) is known to retard aging and delay functional decline as well as the onset of diseases in most organisms. Ghrelin is secreted from the stomach in response to CR and regulates energy metabolism. We hypothesized that in CR ghrelin has a role in protecting aging-related diseases. We examined the physiological mechanisms underlying the ghrelin system during the aging process in three mouse strains with different genetic and biochemical backgrounds as animal models of accelerated or normal human aging. The elevated plasma ghrelin concentration was observed in both klotho-deficient and senescence-accelerated mouse prone/8 (SAMP8) mice. Ghrelin treatment failed to stimulate appetite and prolong survival in klotho-deficient mice, suggesting the existence of ghrelin resistance in the process of aging. However, ghrelin antagonist hastened death and ghrelin signaling potentiators rikkunshito and atractylodin ameliorated several age-related diseases with decreased microglial activation in the brain and prolonged survival in klotho-deficient, SAMP8 and aged ICR mice. In vitro experiments, the elevated sirtuin1 (SIRT1) activity and protein expression through the cAMP-CREB pathway was observed after ghrelin and ghrelin potentiator treatment in ghrelin receptor 1a-expressing cells and human umbilical vein endothelial cells. Furthermore, rikkunshito increased hypothalamic SIRT1 activity and SIRT1 protein expression of the heart in the all three mouse models of aging. Pericarditis, myocardial calcification and atrophy of myocardial and muscle fiber were improved by treatment with rikkunshito. Ghrelin signaling may represent one of the mechanisms activated by CR, and potentiating ghrelin signaling may be useful to extend health and lifespan. PMID- 26830140 TI - Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons. AB - Abnormalities in prefrontal gamma aminobutyric acid (GABA)ergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders, including schizophrenia, bipolar disorder, anxiety disorders and depression. While primarily histological abnormalities have been observed in patients and in animal models of psychiatric disease, evidence for abnormalities in functional neurotransmission at the level of specific interneuron populations has been lacking in animal models and is difficult to establish in human patients. Using an animal model of a psychiatric disease risk factor, prenatal maternal immune activation (MIA), we found reduced functional GABAergic transmission in the medial prefrontal cortex (mPFC) of adult MIA offspring. Decreased transmission was selective for interneurons expressing PV, resulted from a decrease in release probability and was not observed in calretinin expressing neurons. This deficit in PV function in MIA offspring was associated with increased anxiety-like behavior and impairments in attentional set shifting, but did not affect working memory. Furthermore, cell-type specific optogenetic inhibition of mPFC PV interneurons was sufficient to impair attentional set shifting and enhance anxiety levels. Finally, we found that in vivo mPFC gamma oscillations, which are supported by PV interneuron function, were linearly correlated with the degree of anxiety displayed in adult mice, and that this correlation was disrupted in MIA offspring. These results demonstrate a selective functional vulnerability of PV interneurons to MIA, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders. PMID- 26830141 TI - Midbrain functional connectivity and ventral striatal dopamine D2-type receptors: link to impulsivity in methamphetamine users. AB - Stimulant use disorders are associated with deficits in striatal dopamine receptor availability, abnormalities in mesocorticolimbic resting-state functional connectivity (RSFC) and impulsivity. In methamphetamine-dependent research participants, impulsivity is correlated negatively with striatal D2-type receptor availability, and mesocorticolimbic RSFC is stronger than that in controls. The extent to which these features of methamphetamine dependence are interrelated, however, is unknown. This question was addressed in two studies. In Study 1, 19 methamphetamine-dependent and 26 healthy control subjects underwent [18F]fallypride positron emission tomography to measure ventral striatal dopamine D2-type receptor availability, indexed by binding potential (BPND), and functional magnetic resonance imaging (fMRI) to assess mesocorticolimbic RSFC, using a midbrain seed. In Study 2, an independent sample of 20 methamphetamine dependent and 18 control subjects completed the Barratt Impulsiveness Scale in addition to fMRI. Study 1 showed a significant group by ventral striatal BPND interaction effect on RSFC, reflecting a negative relationship between ventral striatal BPND and RSFC between the midbrain and striatum, orbitofrontal cortex and insula in methamphetamine-dependent participants, but a positive relationship in the control group. In Study 2, an interaction of the group with RSFC on impulsivity was observed. Methamphetamine-dependent users exhibited a positive relationship of midbrain RSFC to the left ventral striatum with cognitive impulsivity, whereas a negative relationship was observed in healthy controls. The results indicate that ventral striatal D2-type receptor signaling may affect the system-level activity within the mesocorticolimbic system, providing a functional link that may help explain high impulsivity in methamphetamine dependent individuals. PMID- 26830144 TI - Partitioned airs at microscale and nanoscale: thermal diffusivity in ultrahigh porosity solids of nanocellulose. AB - High porosity solids, such as plastic foams and aerogels, are thermally insulating. Their insulation performance strongly depends on their pore structure, which dictates the heat transfer process in the material. Understanding such a relationship is essential to realizing highly efficient thermal insulators. Herein, we compare the heat transfer properties of foams and aerogels that have very high porosities (97.3-99.7%) and an identical composition (nanocellulose). The foams feature rather closed, microscale pores formed with a thin film-like solid phase, whereas the aerogels feature nanoscale open pores formed with a nanofibrous network-like solid skeleton. Unlike the aerogel samples, the thermal diffusivity of the foam decreases considerably with a slight increase in the solid fraction. The results indicate that for suppressing the thermal diffusion of air within high porosity solids, creating microscale spaces with distinct partitions is more effective than directly blocking the free path of air molecules at the nanoscale. PMID- 26830143 TI - Comparative three-dimensional connectome map of motor cortical projections in the mouse brain. AB - The motor cortex orchestrates simple to complex motor behaviors through its output projections to target areas. The primary (MOp) and secondary (MOs) motor cortices are known to produce specific output projections that are targeted to both similar and different target areas. These projections are further divided into layer 5 and 6 neuronal outputs, thereby producing four cortical outputs that may target other areas in a combinatorial manner. However, the precise network structure that integrates these four projections remains poorly understood. Here, we constructed a whole-brain, three-dimensional (3D) map showing the tract pathways and targeting locations of these four motor cortical outputs in mice. Remarkably, these motor cortical projections showed unique and separate tract pathways despite targeting similar areas. Within target areas, various combinations of these four projections were defined based on specific 3D spatial patterns, reflecting anterior-posterior, dorsal-ventral, and core-capsular relationships. This 3D topographic map ultimately provides evidence for the relevance of comparative connectomics: motor cortical projections known to be convergent are actually segregated in many target areas with unique targeting patterns, a finding that has anatomical value for revealing functional subdomains that have not been classified by conventional methods. PMID- 26830145 TI - The neglected refugee crisis. PMID- 26830142 TI - Prenatal beta-catenin/Brn2/Tbr2 transcriptional cascade regulates adult social and stereotypic behaviors. AB - Social interaction is a fundamental behavior in all animal species, but the developmental timing of the social neural circuit formation and the cellular and molecular mechanisms governing its formation are poorly understood. We generated a mouse model with mutations in two Disheveled genes, Dvl1 and Dvl3, that displays adult social and repetitive behavioral abnormalities associated with transient embryonic brain enlargement during deep layer cortical neuron formation. These phenotypes were mediated by the embryonic expansion of basal neural progenitor cells (NPCs) via deregulation of a beta-catenin/Brn2/Tbr2 transcriptional cascade. Transient pharmacological activation of the canonical Wnt pathway during this period of early corticogenesis rescued the beta catenin/Brn2/Tbr2 transcriptional cascade and the embryonic brain phenotypes. Remarkably, this embryonic treatment prevented adult behavioral deficits and partially rescued abnormal brain structure in Dvl mutant mice. Our findings define a mechanism that links fetal brain development and adult behavior, demonstrating a fetal origin for social and repetitive behavior deficits seen in disorders such as autism. PMID- 26830146 TI - High Resolution Quantitative Angle-Scanning Widefield Surface Plasmon Microscopy. AB - We describe the construction of a prismless widefield surface plasmon microscope; this has been applied to imaging of the interactions of protein and antibodies in aqueous media. The illumination angle of spatially incoherent diffuse laser illumination was controlled with an amplitude spatial light modulator placed in a conjugate back focal plane to allow dynamic control of the illumination angle. Quantitative surface plasmon microscopy images with high spatial resolution were acquired by post-processing a series of images obtained as a function of illumination angle. Experimental results are presented showing spatially and temporally resolved binding of a protein to a ligand. We also show theoretical results calculated by vector diffraction theory that accurately predict the response of the microscope on a spatially varying sample thus allowing proper quantification and interpretation of the experimental results. PMID- 26830147 TI - Facilitating or getting in the way? The effect of clinicians' knowledge, values and beliefs on referral and participation. AB - BACKGROUND: Despite the compelling evidence of the benefits of cardiac rehabilitation (CR) on risk factor modification, quality of life and mortality reduction, a significant proportion of eligible patients are not referred or do not participate. Factors influencing CR referral and participation are complex and are likely patient, referral system and clinician-related. Little is known about clinician-related factors, which include attitudes, values and beliefs towards CR, or how these factors affect patient referral and attendance. This review examines the current evidence in the literature in relation to clinicians' attitudes, values and beliefs about CR. METHODS: A review of the literature was conducted on studies in relation to clinicians' attitudes, values and beliefs toward CR. An expert consensus methodology was used to develop the concepts presented in this paper. RESULTS: Besides guidelines, a range of other factors influence clinicians' view about CR. This review suggests that clinicians lacking cardiac qualifications may have limited knowledge and awareness of CR and its benefits. Low agreement among clinicians on who is more likely to benefit from CR was also identified. Clinicians' personal lifestyle and health belief, the availability and quality of local the CR programme, and the lack of a standard administrative process of referral can also hinder the referral of patients to CR. CONCLUSIONS: Clinician-related factors are important to consider in relation to CR referral and participation. Education for clinicians, discussion of local services and the support of an efficacious system at programme and organisation levels are essential. PMID- 26830148 TI - Compression-only cardiopulmonary resuscitation in improving bystanders' cardiopulmonary resuscitation performance: a literature review. AB - BACKGROUND: Compression-only cardiopulmonary resuscitation (CPR) has been advocated as a preferable approach for bystanders in an out-of-hospital cardiac arrest (OHCA) event as it has been associated with an increased chance of survival. The elimination of mouth-to-mouth ventilation also addresses some of the barriers to performing CPR. The aim of this study is to undertake a literature review investigating the effectiveness of compression-only CPR in improving rescuers' CPR performance when compared with standard CPR. METHODS: A literature search was conducted in the following databases: Cumulative Index to Nursing and Allied Health Literature, Science Direct, Scopus and PubMed from January 2003 to January 2014, to include research studies that compared compression-only CPR with standard CPR on participants above the age of 21, and reported quality of CPR performance as the primary outcome. FINDINGS: Of the 3004 articles retrieved, 16 met the inclusion criteria. The reviewed studies revealed that compression-only CPR requires a shorter time to initiate CPR and delivers a higher number of total compressions. The depth of compressions in compression only CPR performed may be shallower than that of standard CPR due to greater rescuer fatigue. It therefore remains inconclusive if compression-only CPR can deliver a higher number of adequate compressions over extended periods of time. It is also unclear if simplified CPR can improve skill retention level in the long run. CONCLUSIONS: More studies are needed to determine whether compression only CPR can indeed help improve rescuers' CPR performance. Future research efforts, together with resuscitation policy and practice implications, are needed to further improve rescuers' CPR performance with the ultimate goal to enhance OHCA survival rates. PMID- 26830149 TI - Nifuroxazide exerts potent anti-tumor and anti-metastasis activity in melanoma. AB - Melanoma is a highly malignant neoplasm of melanocytes with considerable metastatic potential and drug resistance, explaining the need for new candidates that inhibit tumor growth and metastasis. The signal transducer and activator of the transcription 3 (Stat3) signaling pathway plays an important role in melanoma and has been validated as promising anticancer target for melanoma therapy. In this study, nifuroxazide, an antidiarrheal agent identified as an inhibitor of Stat3, was evaluated for its anti-melanoma activity in vitro and in vivo. It had potent anti-proliferative activity against various melanoma cell lines and could induce G2/M phase arrest and cell apoptosis. Moreover, nifuroxazide markedly impaired melanoma cell migration and invasion by down-regulating phosphorylated Src, phosphorylated-FAK, and expression of matrix metalloproteinase (MMP) -2, MMP 9 and vimentin. It also significantly inhibited tumor growth without obvious side effects in the A375-bearing mice model by inducing apoptosis and reducing cell proliferation and metastasis. Notably, nifuroxazide significantly inhibited pulmonary metastases, which might be associated with the decrease of myeloid derived suppressor cells (MDSCs). These findings suggested that nifuroxazide might be a potential agent for inhibiting the growth and metastasis of melanoma. PMID- 26830151 TI - What is the Asian Consensus Statement on NCCN clinical practice guidelines in oncology (NCCN-ACS)? AB - Cancer treatment guidelines are compiled on the basis of established evidence. Such evidence is obtained from epidemiological, pathological and pharmacological study and, most importantly of all, the information gained from clinical trials. However, very little of the kind of evidence that is required for the compilation of treatment guidelines is actually obtained from Asian countries. When one considers the ethnic differences and disparities in medical care, coupled with the tremendous cultural diversity that characterize the Asian region, it would be difficult to conclude that there is currently sufficient evidence that could form the basis for the formulation of guidelines that would be relevant and applicable to all Asian countries. An urgent issue that needs to be addressed in order to achieve a breakthrough in this difficult situation is to build up a body of evidence at an advanced level that is specific to the Asian region and Asian ethnicities. For the interim, however, it is also necessary to efficiently incorporate evidence that has been obtained in Western countries. Furthermore, an effective method of utilizing guidelines that have already been compiled in Western countries is considered to be not by simply translating them into local languages, but rather to engage in a process of adaptation, whereby the guidelines are adjusted or modified to match the circumstances of a particular country or region. The NCCN Clinical Practice Guidelines-Asian Consensus Statement (NCCN-ACS) documents have been compiled with this intention in mind, utilizing the NCCN guidelines that are widely used internationally. PMID- 26830150 TI - Inter-institutional survival heterogeneity in chemoradiation therapy for esophageal cancer: exploratory analysis of the JCOG0303 study. AB - It is important to examine variation in the treatment effects of patients with esophageal cancer in order to generalize treatment outcomes. We aimed to investigate the range of prognostic differences among hospitals in the treatment of locally advanced esophageal cancer. The JCOG0303 study compared the efficacy of radiotherapy plus low-dose cisplatin and 5-fluorouracil with that of high-dose cisplatin and 5-fluorouracil for unresectable esophageal cancer. Of 32 institutions participating in the JCOG0303 study, the 18 institutions that enrolled three or more patients were included in this study. We predicted the 1 year survival in each institution by using a mixed-effect model. We found that the predicted 1-year survival in the 18 institutions with three or more patients was a median of 60.9%, with a range of 60.9-60.9%. This study is the first to investigated heterogeneity of survival in patients who received definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma. PMID- 26830152 TI - Influence of void-free perovskite capping layer on the charge recombination process in high performance CH3NH3PbI3 perovskite solar cells. AB - The stunning rise of methylammonium lead iodide perovskite material as a light harvesting material in recent years has drawn much attention in the photovoltaic community. Here, we investigated in detail the uniform and void-free perovskite capping layer in the mesoscopic perovskite devices and found it to play a critical role in determining device performance and charge recombination process. Compared to the rough surface with voids of the perovskite layer, surface of the perovskite capping layer obtained from sequential deposition process is much more uniform with less void formation and distribution within the TiO2 mesoscopic scaffold is more homogeneous, leading to much improved photovoltaic parameters of the devices. The impact of void free perovskite capping layer surface on the charge recombination processes within the mesoscopic perovskite solar cells is further scrutinized via charge extraction measurement. Modulation of precursor solution concentrations in order to further improve the perovskite layer surface morphology leads to higher efficiency and lower charge recombination rates. Inhibited charge recombination in these solar cells also matches with the higher charge density and slower photovoltage decay profiles measured. PMID- 26830154 TI - Cell wall as a target for bacteria inactivation by pulsed electric fields. AB - The integrity and morphology of bacteria is sustained by the cell wall, the target of the main microbial inactivation processes. One promising approach to inactivation is based on the use of pulsed electric fields (PEF). The current dogma is that irreversible cell membrane electro-permeabilisation causes the death of the bacteria. However, the actual effect on the cell-wall architecture has been poorly explored. Here we combine atomic force microscopy and electron microscopy to study the cell-wall organization of living Bacillus pumilus bacteria at the nanoscale. For vegetative bacteria, exposure to PEF led to structural disorganization correlated with morphological and mechanical alterations of the cell wall. For spores, PEF exposure led to the partial destruction of coat protein nanostructures, associated with internal alterations of cortex and core. Our findings reveal for the first time that the cell wall and coat architecture are directly involved in the electro-eradication of bacteria. PMID- 26830155 TI - Collaborative study for the calibration of the Ph. Eur. prekallikrein activator in albumin BRP batches 4, 5 and 6. AB - An international collaborative study was organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM, Council of Europe) to calibrate replacement batches for the current European Pharmacopoeia (Ph. Eur.) prekallikrein activator (PKA) in albumin biological reference preparation (BRP), whose stocks were dwindling. The study was run in the framework of the Biological Standardisation Programme (BSP) of the Council of Europe and the European Union (EU) Commission. Twenty three laboratories from official medicines control authorities and manufacturers in Europe and outside Europe took part in the study. Three candidate replacement batches were produced from the same material as the one used for the World Health Organization (WHO) 2(nd) International Standard (IS) for PKA in albumin (02/168) and the Ph. Eur. PKA in albumin BRP batches 1, 2 and 3. Participants were requested to evaluate the candidate batches against the current WHO IS using their routine assay method. The Ph. Eur. PKA in albumin BRP batch 3 (BRP3) was also included in the test panel to ensure the continuity of the consecutive BRP batches. The study confirmed the stability of the PKA content of the current BRP3. The candidate batches were found to be comparable. Previous data on the starting material support its high stability. Thermal stress study on the candidate batches confirmed the stability of their PKA activity. The Commission of the Ph. Eur. officially adopted in November 2013 the 3 candidate batches as Ph. Eur. PKA in albumin BRP batches 4, 5 and 6 with an assigned content of 38 IU/vial. The activity of the 3 new batches of Ph. Eur. PKA in albumin BRP will be regularly monitored. PMID- 26830156 TI - Determination of the purity of valine by isocratic liquid chromatography coupled with charged aerosol detection (CAD). AB - A liquid chromatography coupled with charged aerosol detection (LC-CAD) procedure; capable of separating and quantifying the most common impurities of valine at levels as low as 0.05 per cent (m/m), has been developed. The procedure is simple (isocratic), rapid, linear, sensitive and repeatable. It employs a widely available and inexpensive stationary phase (C18). PMID- 26830157 TI - Quantification of low levels of methionine oxidation in erythropoietin drug substance. AB - A pharmacopoeial monograph under development for recombinant human erythropoietin (rhEPO) drug substance is likely to contain a specification limit for the proportion of the methionine-oxidised variant. Methionine oxidation has no effect on the folded structure and global thermodynamic stability of rhEPO but can decrease biological activity [1]. We describe here the development of a reference standard, a calibrated mixture of the native and oxidised tryptic peptides which contain methionine-54, and an optimised peptide mapping procedure to support this assay. The approach may be developed for analysis of drug product or generalised for other assays in which product-related impurities are quantified by peptide mapping. PMID- 26830158 TI - The vaccines consistency approach project: an EPAA initiative. AB - The consistency approach for release testing of established vaccines promotes the use of in vitro, analytical, non-animal based systems allowing the monitoring of quality parameters during the whole production process. By using highly sensitive non-animal methods, the consistency approach has the potential to improve the quality of testing and to foster the 3Rs (replacement, refinement and reduction of animal use) for quality control of established vaccines. This concept offers an alternative to the current quality control strategy which often requires large numbers of laboratory animals. In order to facilitate the introduction of the consistency approach for established human and veterinary vaccine quality control, the European Partnership for Alternatives to Animal Testing (EPAA) initiated a project, the "Vaccines Consistency Approach Project", aiming at developing and validating the consistency approach with stakeholders from academia, regulators, OMCLs, EDQM, European Commission and industry. This report summarises progress since the project's inception. PMID- 26830159 TI - EDQM biological reference preparation for rabies vaccine (inactivated) for veterinary use. AB - Rabies is a deadly zoonotic disease. Control of rabies in animals by vaccination is an important strategy to protect humans from infection and control the spread of the disease. Requirements for the quality control of rabies vaccines (inactivated) for veterinary use include an in vivo quantitative potency determination as outlined in the Ph. Eur. monograph 0451. Performance of this assay requires a reference preparation calibrated in International Units (IU). A European Pharmacopeia (Ph. Eur.) Biological Reference Preparation (BRP) for rabies vaccines (inactivated) for veterinary use, calibrated in IU, has been established for this purpose. Due to the dwindling stocks of the current batch (batch 4) of Ph. Eur. BRP for rabies vaccines (inactivated) for veterinary use, a collaborative study was run as part of the EDQM Biological Standardisation Programme to establish BRP batch 5. Ten laboratories, including Official Medicines Control Laboratories and manufacturers, participated. The candidate BRP5 was assayed against the 6(th) International Standard for rabies vaccine using the in vivo vaccination-challenge assay (monograph 0451) to assign a potency value. The candidate was also compared to BRP batch 4 to establish continuity. Taking into account the results from the comparisons a potency of 10 IU/vial was assigned and in March 2015 the Ph. Eur. Commission adopted the material as Ph. Eur. BRP for rabies vaccines (inactivated) for veterinary use batch 5. In addition to the in vivo assay 3 laboratories tested the candidate material using their in-house in vitro assays for information. PMID- 26830160 TI - Collaborative study for the establishment of the WHO 3(rd) International Standard for Endotoxin, the Ph. Eur. endotoxin biological reference preparation batch 5 and the USP Reference Standard for Endotoxin Lot H0K354. AB - An international collaborative study was organised jointly by the World Health Organization (WHO)/National Institute for Biological Standards and Control (NIBSC), the United States Pharmacopeia (USP) and the European Directorate for the Quality of Medicines & HealthCare (EDQM/Council of Europe) for the establishment of harmonised replacement endotoxin standards for these 3 organisations. Thirty-five laboratories worldwide, including Official Medicines Control Laboratories (OMCLs) and manufacturers enrolled in the study. Three candidate preparations (10/178, 10/190 and 10/196) were produced with the same material and same formulation as the current reference standards with the objective of generating a new (3(rd)) International Standard (IS) with the same potency (10 000 IU/vial) as the current (2(nd)) IS, as well as new European Pharmacopoeia (Ph. Eur.). and USP standards. The suitability of the candidate preparations to act as the reference standard in assays for endotoxin performed according to compendial methods was evaluated. Their potency was calibrated against the WHO 2(nd) IS for Endotoxin (94/580). Gelation and photometric methods produced similar results for each of the candidate preparations. The overall potency estimates for the 3 batches were comparable. Given the intrinsic assay precision, the observed differences between the batches may be considered unimportant for the intended use of these materials. Overall, these results were in line with those generated for the establishment of the current preparations of reference standards. Accelerated degradation testing of vials stored at elevated temperatures supported the long-term stability of the 3 candidate preparations. It was agreed between the 3 organisations that batch 10/178 be shared between WHO and EDQM and that batches 10/190 and 10/196 be allocated to USP, with a common assigned value of 10 000 IU/vial. This value maintains the continuity of the global harmonisation of reference materials and unitage for the testing of endotoxins in parenteral pharmaceutical products. Based on the results of the collaborative study, batch 10/178 was established by the European Pharmacopoeia Commission as the Ph. Eur. Endotoxin Biological Reference Preparation (BRP) batch 5. The same batch was also established by the Expert Committee on Biological Standardisation (ECBS) of WHO as the WHO 3(rd) IS for Endotoxin. Batch 10/190 was adopted as the USP Endotoxin Reference Standard, lot H0K354 and vials from this same batch (10/190) will serve as the United States Food and Drug Administration (USFDA) Endotoxin Standard, EC-7. PMID- 26830161 TI - Establishment of the Ph. Eur. erythropoietin chemical reference substance batch 1. AB - The Erythropoietin (EPO) European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) batch 3 was calibrated in 2006 by in vivo bioassay and was used as a reference preparation for these assays as well as for the physicochemical methods in the Ph. Eur. monograph Erythropoietin concentrated solution (1316). In order to avoid the frequent replacement of this standard and thus reduce the use of animals, a new EPO Chemical Reference Substance (CRS) was established to be used solely for the physicochemical methods. Here we report the outcome of a collaborative study aimed at demonstrating the suitability of the candidate CRS (cCRS) as a reference for the physicochemical methods in the Ph. Eur. monograph. Results from the study demonstrated that for the physicochemical methods currently required in the monograph (capillary zone electrophoresis (CZE), polyacrylamide gel electrophoresis (PAGE)/immunoblotting and peptide mapping), the cCRS is essentially identical to the existing BRP. However, data also indicated that, for the physicochemical methods under consideration for inclusion in a revised monograph (test for oxidised forms and glycan mapping), the suitability of the cCRS as a reference needs to be confirmed with additional work. Further to completion of the study, the Ph. Eur. Commission adopted the cCRS as "Erythropoietin for physicochemical tests CRS batch 1" to be used for CZE, PAGE/immunoblotting and peptide mapping. PMID- 26830162 TI - Establishment of hepatitis A vaccine (inactivated, non-adsorbed) BRP batches 2 and 3. AB - The current hepatitis A vaccine (HAV), inactivated, non-adsorbed, European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) is used for the in vitro potency assay of HAV as prescribed by the Ph. Eur. general chapter 2.7.14 Assay of hepatitis A vaccine. This reference preparation was calibrated in 2008 through an international collaborative study and was assigned a potency of 12 IU/mL. During use of this BRP it appeared to be inapplicable in certain cases due to a low nominal antigen content. Consequently, the European Directorate for the Quality of Medicines and HealthCare (EDQM) established replacement batches for this BRP, calibrated against the 1(st) WHO International Standard (IS) for HAV (inactivated), using the standard in vitro ELISA (enzyme-linked immunosorbent assay) method validated previously. The results of the study showed that the candidate BRPs were suitable for the intended purpose, and following completion of the study, they were adopted in November 2014 by the Ph. Eur. Commission as HAV (inactivated, non-adsorbed) BRP batches 2 and 3, with an assigned potency of 1350 IU/mL, for in vitro antigen content determination by ELISA. As the amount of material in each vial largely exceeds the amount required for the performance of a single assay, the BRPs are to be aliquoted by users as single-use aliquots and refrozen below -50 degrees C prior to their use as reference preparations. PMID- 26830163 TI - Pesticide residues in essential oils: evaluation of a database. AB - In the context of a revision of the European Pharmacopoeia (Ph. Eur.) general monograph Essential oils (2098), the need to include a test for pesticides is being discussed. According to published literature, some oils, mainly those produced by cold pressing (e.g. citrus oils), can contain relevant amounts of pesticide residues, whereas distilled oils showed positive findings in only a few cases. Recent evaluation of a database containing 127 517 sets of data compiled over 8 years, showed positive results in 1 150 cases (0.90 per cent), and the limits of Ph. Eur. general chapter 2.8.13 Pesticide residues or Regulation (EC) 396/2005, both applicable to herbal drugs, were exceeded in 392 cases (0.31 per cent, equivalent to 34.1 per cent of the positive results), particularly in cases of oils produced by cold pressing. From these results, it can be concluded that a general test on pesticides in the Ph. Eur. general monograph on essential oils is not required for most oils used in medicinal products. Therefore, it is proposed to limit the testing of essential oils for pesticide residues to those cases where potential residues are more of a concern, either due to the type of production process or to those processes where pesticides are actively used during cultivation of the plant (e.g. as documented according to Good Agricultural and Collection Practice (GACP)). Furthermore, in order to assess any potential risk, an approach using the Acceptable Daily Intake (ADI) can be made. PMID- 26830164 TI - The heavy metals cadmium, lead and mercury in raw materials of animal origin: evaluation of data from practice. AB - Raw materials from animal origin are widely used in homoeopathy. Due to the lack of dedicated limits, the quality requirements for herbal drugs of the European Pharmacopoeia (Ph. Eur.) and/or the German Homoeopathic Pharmacopoeia (Homoopathisches Arzneibuch, HAB), including limits for heavy metals such as cadmium, lead and mercury, have been applied. A recent database evaluation shows that for some raw materials of animal origin the Ph. Eur. limits for herbal drugs cannot be met in practice. For this reason proposals for new limits for cadmium, lead and mercury are made based on recent experiences from the companies' daily practice. These specific limits are suggested to be included in the individual monographs of the Ph. Eur. or at least the German HAB, respectively, for Ambra grisea, Euspongia officinalis, Formica rufa and Sepia officinalis. PMID- 26830165 TI - Rationale for the update of the European Pharmacopoeia general chapter 2.2.48. Raman spectroscopy. AB - Raman spectroscopy technique is widely used for the identification and characterisation of materials in the laboratory environment and, increasingly, for off-line, at-line, in-line and online Process Analytical Technologies (PAT) applications. The wide range of currently available Raman technologies had led to the requirement to update the existing General Chapter 2.2.48. The purpose of this reflection paper is to explain the rationale behind the establishment of the new wavenumber scale standards and peak position tolerances resulting from a multi-site, multi-instrument, inter-laboratory study of standards and, in particular, to discuss the results obtained with microscopes (including multi point calibration) by the PAT Working Party. PMID- 26830166 TI - Establishment of the human albumin for electrophoresis Ph. Eur. BRP batches 3 and 4. AB - Due to the diminished stocks of the 2nd batch of the European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for human albumin for electrophoresis, the European Directorate for the Quality of Medicines & HealthCare (EDQM) initiated in 2014 an international collaborative study for the establishment of two replacement batches. The study was run under the aegis of the Biological Standardisation Programme (BSP). Thirteen laboratories participated in the collaborative study to verify the suitability of the candidate reference preparations according to the Ph. Eur. monograph 0255 using the zone electrophoresis (ZE) method with either cellulose acetate and/or agarose as the testing medium. The candidate preparations were found suitable for the intended purpose and were subsequently adopted in June 2015 by the Ph. Eur. Commission as human albumin for electrophoresis BRP batches 3 and 4 with an assigned range for albumin of 93.8 per cent to 98.3 per cent of the total protein content. PMID- 26830167 TI - Collaborative study for the establishment of the 4(th) International Standard for Streptomycin. AB - An international collaborative study was organised to establish the 4(th) World Health Organization (WHO) International Standard (IS) for Streptomycin. Fourteen laboratories from different countries participated. Potencies of the candidate material were estimated by microbiological assays with sensitive micro-organisms. To ensure continuity between consecutive batches, the 3(rd) IS for Streptomycin was used as a reference. Based on the results of the study, the 4(th) IS for Streptomycin was adopted at the meeting of the WHO Expert Committee for Biological Standardization (ECBS) in 2015 with an assigned potency of 76 000 International Units (IU) per vial. The 4(th) IS for Streptomycin is available from the European Directorate for the Quality of Medicines & HealthCare (EDQM). PMID- 26830168 TI - Collaborative study for the establishment of the 2(nd) International Standard for Bleomycin Complex A2/B2. AB - Organization (WHO) International Standard (IS) for bleomycin complex A2/B2. Eight laboratories from different countries participated. Potencies of the candidate material were estimated by microbiological assays with sensitive micro-organisms. To ensure continuity between consecutive batches, the 1(st) IS for bleomycin complex A2/B2 was used as a reference. Based on the results of the study, the 2(nd) IS for bleomycin complex A2/B2 was adopted at the meeting of the WHO Expert Committee for Biological Standardization (ECBS) in 2014 with an assigned potency of 12 500 International Units (IU) per vial. The 2(nd) IS for bleomycin complex A2/B2 is available from the European Directorate for the Quality of Medicines & HealthCare (EDQM). PMID- 26830169 TI - Establishment of hepatitis A detection antibodies set BRR batch 3 for antigen content determination by ELISA. AB - The current batch of the European Pharmacopoeia (Ph. Eur.) Biological Reference Reagents (BRRs) used for the in vitro potency assay of hepatitis A vaccines (HAV) by ELISA (enzymelinked immunosorbent assay) was established in 2012 for use in conjunction with Ph. Eur. general chapter 2.7.14 Assay of hepatitis A vaccine. It is composed of a coating reagent and a set of detection antibodies. As stocks of the latter are running low, the European Directorate for the Quality of Medicines & HealthCare (EDQM) organised a collaborative study to qualify replacement batches. The candidate BRR antibodies (primary monoclonal antibody and labelled secondary antibody) were prepared under appropriate conditions from starting materials similar to those used for the current batches. The new batches of antibodies were tested alongside previous batches of BRRs to ensure continuity, and the results confirmed that they were suitable for use in the potency assay of hepatitis A vaccines by ELISA using the standard method referenced in Ph. Eur. general chapter 2.7.14 at the same final concentrations as the previous batches, i.e. 1:500 for the primary monoclonal antibody and 1:400 for the secondary conjugated antibody. The outcome of the study allowed their establishment by the Ph. Eur. Commission in March 2015 as anti-hepatitis A virus primary detection antibody BRR batch 3 and conjugated secondary detection antibody BRR batch 3 respectively. They are available from the EDQM as hepatitis A vaccine ELISA detection antibodies set BRR batch 3. PMID- 26830170 TI - Collaborative study for the establishment of erythropoietin BRP batch 4. AB - The European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for erythropoietin (EPO) is used as a working standard for potency determination of EPO preparations by in vivo bioassay as prescribed in the Ph. Eur. monograph Erythropoietin concentrated solution (1316). The BRP batch 3 was calibrated in 2006 and its stocks are depleted. The European Directorate for the Quality of Medicines & HealthCare (EDQM) thus initiated a project to calibrate a replacement batch in International Units against the WHO 3(rd) International Standard (IS) for Erythropoietin, recombinant, for bioassay (11/170). A Ph. Eur. Chemical Reference Substance (CRS) was established recently for use as reference in some of the physicochemical tests prescribed in the monograph. Therefore, the EPO BRP batch 4 was only calibrated for the normocythaemic and polycythaemic mouse in vivo bioassays described in the Assay section of the Ph. Eur. monograph (1316). The collaborative study involved seven laboratories from Europe, the USA and South America. The results confirmed that the candidate BRP (cBRP) is suitable for use as a reference preparation in the potency determination of EPO medicinal products by bioassay (using the normocythaemic or polycythaemic mouse methods). The outcome of the study enabled the Ph. Eur. Commission to establish the proposed standard as erythropoietin BRP batch 4 in November 2014 for use as a reference preparation solely for the polycythaemic and normocythaemic mouse bioassay, with an assigned potency of 13 000 IU/vial. Furthermore, the potency of BRP3 was confirmed during the study, thus warranting a good continuity of the IU. PMID- 26830171 TI - Phenanthrene exposure induces cardiac hypertrophy via reducing miR-133a expression by DNA methylation. AB - Growing evidence indicates that there is an emerging link between environmental pollution and cardiac hypertrophy, while the mechanism is unclear. The objective of this study was to examine whether phenanthrene (Phe) could cause cardiac hypertrophy, and elucidate the molecular mechanisms involved. We found that: 1) Phe exposure increased the heart weight and cardiomyocyte size of rats; 2) Phe exposure led to enlarged cell size, and increased protein synthesis in H9C2 cells; 3) Phe exposure induced important markers of cardiac hypertrophy, such as atrial natriuretic peptide, B-type natriuretic peptide, and c-Myc in H9C2 cells and rat hearts; 4) Phe exposure perturbed miR-133a, CdC42 and RhoA, which were key regulators of cardiac hypertrophy, in H9C2 cells and rat hearts; 5) Phe exposure induced DNA methyltransferases (DNMTs) in H9C2 cells and rat hearts; 6) Phe exposure led to methylation of CpG sites within the miR-133a locus and reduced miR-133a expression in H9C2 cells; 7) DNMT inhibition and miR-133a overexpression could both alleviate the enlargement of cell size and perturbation of CdC42 and RhoA caused by Phe exposure. These results indicated that Phe could induce cardiomyocyte hypertrophy in the rat and H9C2 cells. The mechanism might involve reducing miR-133a expression by DNA methylation. PMID- 26830172 TI - Erratum to: Adjuvant Radioactive iodine 131 ablation in papillary microcarcinoma of thyroid: Saudi Arabian experience. PMID- 26830175 TI - When It's Your Time, Will It Be Your Way? PMID- 26830176 TI - Corrections. AB - In the October In Our Unit article by Cooper et al, "Against All Odds: Preventing Pressure Ulcers in High-Risk Cardiac Surgery Patients" (Crit Care Nurse. 2015;35[5]:76-82), there was an error in the reference citation on page 82. At the top of that page, reference 18 cited on the second line should be reference 23, which also should be added to the References list: 23. AHRQ website. Prevention and treatment program integrates actionable reports into practice, significantly reducing pressure ulcers in nursing home residents. November 2008. https://innovations.ahrq.gov/profiles/prevention-and-treatment-program-integrates actionable-reports-practice-significantly. Accessed November 18, 2015 PMID- 26830173 TI - Risk factors for intensive care unit admission in patients with severe leptospirosis: a comparative study according to patients' severity. AB - BACKGROUND: The aim of this study is to investigate predictive factors for intensive care unit (ICU) admission among patients with severe leptospirosis. METHODS: This is a retrospective study with all patients with severe leptospirosis admitted to a tertiary hospital. Patients were divided in ICU and ward groups. Demographical, clinical and laboratory data of the groups were compared as well as acute kidney injury (AKI) severity, according to the RIFLE criteria (R = Risk, I = Injury, F = Failure, L = Loss, E = End-stage kidney disease). RESULTS: A total of 206 patients were included, 83 admitted to ICU and 123 to ward. Mean age was 36 +/- 15.8 years, with 85.9% males. Patients in ICU group were older (38.8 +/- 15.7 vs. 34.16 +/- 15.9 years, p = 0.037), had a shorter hospital stay (4.13 +/- 3.1 vs. 9.5 +/- 5.2 days, p = 0.0001), lower levels of hematocrit (29.6 +/- 6.4 vs. 33.1 +/- 8.6%, p = 0.003), hemoglobin (10.2 +/- 2.4 vs. 11.6 +/- 1.9 g/dL, p < 0.0001), and platelets (94,427 +/- 86,743 vs. 128,896 +/- 137,017/mm(3), p = 0.035), as well as higher levels of bilirubin (15.0 +/- 12.2 vs. 8.6 +/- 9.5 mg/dL, p = 0.001). ICU group also had a higher frequency of severe AKI (RIFLE-"Failure": 73.2% vs. 54.2%, p < 0.0001) and a higher prevalence of dialysis requirement (57.3% vs. 27.6%, p < 0.0001). Mortality was higher among ICU patients (23.5% vs. 5.7%, p < 0.0001). Independent predictors for ICU admission were tachypnea (p = 0.027, OR = 13, CI = 1.3-132), hypotension (p = 0.009, OR = 5.27, CI = 1.5-18) and AKI (p = 0.029, OR = 14, CI = 1.3-150). Ceftriaxone use was a protective factor (p = 0.001, OR = 0.13, CI = 0.04-0.4). CONCLUSIONS: Independent risk factors for ICU admission in leptospirosis include tachypnea, hypotension and AKI. Ceftriaxone was a protective factor for ICU admission, suggesting that its use may prevent severe forms of the disease. PMID- 26830177 TI - Acute Coronary Syndrome: Focus on Antiplatelet Therapy. AB - The American Heart Association/American College of Cardiology in 2014 published a focused update of the 2007 and 2012 guidelines for non-ST-segment elevation acute coronary syndrome (NSTE-ACS). The management of ST-segment elevation myocardial infarction (STEMI) is described in a separate guideline published in 2013. The focused updates to the guidelines contain updated recommendations for dual antiplatelet therapy, including use of the P2Y12 inhibitor ticagrelor, which was recently approved by the Food and Drug Administration. Nurses caring for patients with acute coronary syndrome must have a good understanding of the current treatment guidelines for such patients, to help ensure delivery of evidence-based care. This review article uses a case study-based approach to describe how the new guidelines affect clinical decision making when choosing appropriate antiplatelet therapy for patients with NSTE-ACS or STEMI, depending on the patient's clinical history and presenting characteristics. PMID- 26830178 TI - Alcohol Withdrawal Syndrome in Critically Ill Patients: Identification, Assessment, and Management. AB - Management of alcohol withdrawal in critically ill patients is a challenge. The alcohol consumption histories of intensive care patients are often incomplete, limiting identification of patients with alcohol use disorders. Abrupt cessation of alcohol places these patients at risk for alcohol withdrawal syndrome. Typically benzodiazepines are used as first-line therapy to manage alcohol withdrawal. However, if patients progress to more severe withdrawal or delirium tremens, extra adjunctive medications in addition to benzodiazepines may be required. Sedation and mechanical ventilation may also be necessary. Withdrawal assessment scales such as the Clinical Institute of Withdrawal Assessment are of limited use in these patients. Instead, general sedation-agitation scales and delirium detection tools have been used. The important facets of care are the rapid identification of at-risk patients through histories of alcohol consumption, management with combination therapies, and ongoing diligent assessment and evaluation. (Critical Care Nurse. 2016;36[1]:28-39). PMID- 26830179 TI - Control of Traumatic Extremity Hemorrhage. AB - Although most extremity hemorrhage from trauma can be controlled with direct pressure and/or pressure dressings, the occasional uncontrolled hemorrhage can be life threatening. Tools that may be able to control such life-threatening extremity hemorrhage include hemostatic dressings, tourniquets, and several new devices that have recently become available. Hemostatic dressings, a relatively new concept, incorporate materials that increase coagulation into a dressing that is applied directly to the wound. Although the use of tourniquets has a long history, recent military conflicts have provided numerous studies that supported and refined their use. The novel extremity hemorrhage control devices effectively control bleeding in one of several ways: direct compression, arterial compression above the level of injury, and sealing the wounds' edges, creating a hematoma. PMID- 26830180 TI - Preoperative Stabilization of Infants With Hypoplastic Left Heart Syndrome Before Stage I Palliation. AB - Hypoplastic left heart syndrome is a severe form of congenital heart disease that results in single-ventricle physiology. Although surgical palliation in infants with this syndrome is widely agreed on in practice, variation occurs in both surgical and medical management. Perinatal factors that affect preoperative management include the subtype of the syndrome and the patient's birth weight, gestational age, and genetic abnormalities. The general aspects of perioperative stabilization and management are monitoring, use of vasoactive infusions, ventilatory support, and nutrition. Management strategies for balancing single ventricle physiology are aimed at addressing the 3 major causes of desaturation: diminished pulmonary blood flow, low mixed venous oxygen saturation, and pulmonary venous desaturation. PMID- 26830181 TI - Implementing Electronic Tablet-Based Education of Acute Care Patients. AB - Poor education-related discharge preparedness for patients with heart failure is believed to be a major cause of avoidable rehospitalizations. Technology-based applications offer innovative educational approaches that may improve educational readiness for patients in both inpatient and outpatient settings; however, a number of challenges exist when implementing electronic devices in the clinical setting. Implementation challenges include processes for "on-boarding" staff, mediating risks of cross-contamination with patients' device use, and selling the value to staff and health system leaders to secure the investment in software, hardware, and system support infrastructure. Strategies to address these challenges are poorly described in the literature. The purpose of this article is to present a staff development program designed to overcome challenges in implementing an electronic, tablet-based education program for patients with heart failure. PMID- 26830182 TI - Palliative Care in Critical Rural Settings. AB - The United States has 1332 critical access hospitals. These hospitals have fewer than 25 beds each and a mean daily census of 4.2 patients. Critical access hospitals are located in rural areas and provide acute inpatient services, ambulatory care, labor and delivery services, and general surgery. Some, but not all, critical access hospitals offer home care services; a few have palliative care programs. Because of the millions of patients living with serious and life threatening conditions, the need for palliative care is increasing. As expert generalists, rural nurses are well positioned to provide care close to home for patients of all ages and the patients' families. A case report illustrates the role that nurses and critical access hospitals play in meeting the need for high quality palliative care in rural settings. Working together, rural nurses and their urban nursing colleagues can provide palliative care across all health care settings. PMID- 26830183 TI - Certification: A C edential of Competence. PMID- 26830184 TI - Administering Medications During Targeted Temperature Management. PMID- 26830186 TI - I Am a Critical Care Nurse. PMID- 26830185 TI - Rapid Response Teams Decreasing Intubation and Code Blue Rates Outside the Intensive Care Unit. PMID- 26830187 TI - A Bedside Decision Tree for Use of Saline With Endotracheal Tube Suctioning in Children. AB - BACKGROUND: Endotracheal tube suctioning is necessary for patients receiving mechanical ventilation. Studies examining saline instillation before suctioning have demonstrated mixed results. METHODS: A prospective study to evaluate whether saline instillation is associated with an increased risk of suctioning-related adverse events in patients 18 years old or younger requiring mechanical ventilation through an endotracheal tube for at least 48 hours when suctioned per protocol using a bedside decision tree. RESULTS: A total of 1986 suctioning episodes (1003 with saline) were recorded in 69 patients. The most common indication for use of saline was thick secretions (87% of episodes). In 586 suctioning episodes, at least 1 adverse event occurred with increased frequency in the saline group (P < .001). Normal saline was more likely to be associated with hemodynamic instability (P = .04), bronchospasm (P < .001), and oxygen desaturation (P < .001). Patient factors associated with adverse events include younger age (P < .001), a cuffed endotracheal tube (P = .001), endotracheal tube diameter of 4.0 mm or less (P < .001), respiratory or hemodynamic indication for intubation (P < .001), underlying respiratory disease (P < .001), and longer duration of mechanical ventilation (P < .001). Saline instillation (P < .001), endotracheal tube size of 4.0 mm or less (P = .03), and comorbid respiratory diseases (P = .03) were associated with an increased risk of adverse events. CONCLUSIONS: Saline instillation before endotracheal tube suctioning is associated with hemodynamic instability, bronchospasm, and transient hypoxemia. Saline should be used cautiously, especially in children with a small endotracheal tube and comorbid respiratory disease. PMID- 26830188 TI - Family Presence During Resuscitation and Invasive Procedures. PMID- 26830189 TI - Family Visitation in the Adult Intensive Care Unit. PMID- 26830190 TI - Prevention of Aspiration in Adults. PMID- 26830191 TI - Research participation after terrorism: an open cohort study of survivors and parents after the 2011 Utoya attack in Norway. AB - BACKGROUND: Reliable estimates of treatment needs after terrorism are essential to develop an effective public health response. More knowledge is required on research participation among survivors of terrorism to interpret the results properly and advance disaster research methodology. This article reports factors associated with participation in an open cohort study of survivors of the Utoya youth camp attack and their parents. METHODS: Overall, 490 survivors were invited to two semi-structured interviews that were performed 4-5 and 14-15 months after the attack. The parents of 482 survivors aged 13-32 years were eligible for a complementary study. The study had an open cohort design in which all of the eligible survivors were invited to both waves. Pearson's Chi squared tests (categorical variables) and independent t tests (continuous variables) were used to compare survivors by participation. RESULTS: Altogether, 355 (72.4 %) survivors participated: 255 in both waves, 70 in wave 1 only, and 30 in wave 2 only. Compared with the two-wave participants, wave-1-only participants were more often non-Norwegian and reported higher exposure, whereas wave-2-only participants reported more posttraumatic stress, anxiety/depression, and somatic symptoms. In total, 331 (68.7 %) survivors had >=1 participating parents, including 311 (64.5 %) with maternal and 243 (50.4 %) with paternal participation. Parental non-participation was associated with non-Norwegian origin, somatic symptoms and less social support. Additionally, paternal non participation was associated with having divorced parents, and maternal non participation was associated with higher age, not living with parents, posttraumatic stress and anxiety/depression symptoms. CONCLUSIONS: Survivors with initial non-participation had more symptoms than did the other participants. Thus, an open cohort design in post-terrorism studies might improve the participation among survivors with higher morbidity. Because the factors associated with maternal and paternal participation differed, it is important to consider potential disparities in the selection of mothers and fathers when interpreting parental data. PMID- 26830192 TI - Metallic Fabrics as the Current Collector for High-Performance Graphene-Based Flexible Solid-State Supercapacitor. AB - Flexible solid-state supercapacitors attract more and more attention as the power supply for wearable electronics. To fabricate such devices, the flexible and economical current collectors are needed. In this paper, we report the stainless steel fabrics as the current collector for high-performance graphene-based supercapacitors. The stainless steel fabrics have superior properties compared with the widely used flexible current collectors. The flexible supercapacitors show large specific capacitance of 180.4 mF/cm(2), and capacitance retention of 96.8% after 7500 charge-discharge cycles. Furthermore, 96.4% of the capacitance is retained after 800 repeating stretching-bending cycles. The high performance is related to the excellent conductivity, good mechanical flexibility, and high electrochemical stability of the stainless steel fabrics. The achievement of such high-performance and flexible supercapacitor can open up exciting opportunities for wearable electronics and energy storage applications. PMID- 26830193 TI - In-hospital free fatty acids levels predict the severity of myocardial ischemia of acute coronary syndrome. AB - BACKGROUND: We aimed to assess whether the levels of FFAs (free fatty acids) in ACS (acute coronary syndrome) patients depend on the extent of myocardial ischemia during the subacute phase of ACS attack. METHODS: A total of 892 consecutive CAD (coronary artery disease) subjects undergoing coronary angiography were enrolled. The FFAs contents were measured based on enzymatic assay. The relationship between FFAs and Gensini score and ACS susceptibility was assessed. RESULTS: In the overall population, the upper FFAs quartile was accompanied with higher ischemia parameters and increased occurrence of ACS and STEMI (ST-segment elevation myocardial infarction) (P < 0.05). The FFAs concentrations were approximately 1.5-fold higher in ACS than in stable CAD patients, roughly 1.3-fold higher in STEMI than non-STEMI ACS patients and probably 1.3-fold higher in non-STEMI ACS than in stable CAD patients. After adjusted for traditional cardiovascular risk factors, the FFAs level remained a risk factor for a higher Gensini score with more than 40 (P < 0.001) and prevalent ACS (P < 0.001). After adjusted for traditional risk factors, FFAs levels after natural logarithm transformation were associated with hs-CRP and WBC counts in ACS patients. A multiplicative interaction was found between hs-CRP, WBC counts and FFAs in incident ACS and higher Gensini score (P < 0.001). CONCLUSIONS: Higher in-hospital levels of FFAs persist and may reflect the severity of ischemia and necrosis during the subacute phase of ACS attack. PMID- 26830194 TI - Prevalence, correlates and patterns of waterpipe smoking among secondary school students in southeast London: a cross-sectional study. AB - BACKGROUND: Waterpipe smoking is growing worldwide, but little is known of its epidemiology in the UK due to its absence from national health surveys. We sought to address this by calculating the prevalence of waterpipe smoking among secondary school students in southeast London. METHODS: We conducted a pooled secondary analysis of routine health surveillance surveys among 11-17 year olds in convenience-sampled secondary schools from three ethnically-diverse areas of southeast London. We calculated ever (lifetime) waterpipe use, and compared its sociodemographic correlates to ever (lifetime) cigarette use. In one area we collected data on patterns of waterpipe use. RESULTS: Of 2,098 respondents (mean age 14.1 +/- 1.7 years, 55.7 % male, 46.6 % of black ethnicity), ever waterpipe use was 39.6 % (95 % CI 37.6-41.7 %) and was higher than that for ever cigarette use (32.4 %; 95 % CI 30.5-34.4). While waterpipe users were significantly and independently more likely to be male and of non-white ethnicities, at least 30 % of all age, gender and ethnic sub-groups had tried waterpipe smoking. In contrast, cigarette users were more likely to be older and of white ethnicity. In one of the three areas, over a quarter of waterpipe users were occasional or regular waterpipe smokers, and most were introduced to and currently used waterpipe in waterpipe-serving premises or friends' homes. CONCLUSIONS: Waterpipe smoking prevalence was high in southeast London, and users exhibited a different sociodemographic profile to cigarette users. Waterpipe should be included in national health surveys of young people. National surveillance is warranted to help develop suitable interventions to prevent uptake and promote cessation. PMID- 26830195 TI - Depression and postoperative complications: an overview. AB - BACKGROUND: The interaction of depression and anesthesia and surgery may result in significant increases in morbidity and mortality of patients. Major depressive disorder is a frequent complication of surgery, which may lead to further morbidity and mortality. LITERATURE SEARCH: Several electronic data bases, including PubMed, were searched pairing "depression" with surgery, postoperative complications, postoperative cognitive impairment, cognition disorder, intensive care unit, mild cognitive impairment and Alzheimer's disease. REVIEW OF THE LITERATURE: The suppression of the immune system in depressive disorders may expose the patients to increased rates of postoperative infections and increased mortality from cancer. Depression is commonly associated with cognitive impairment, which may be exacerbated postoperatively. There is evidence that acute postoperative pain causes depression and depression lowers the threshold for pain. Depression is also a strong predictor and correlate of chronic post surgical pain. Many studies have identified depression as an independent risk factor for development of postoperative delirium, which may be a cause for a long and incomplete recovery after surgery. Depression is also frequent in intensive care unit patients and is associated with a lower health-related quality of life and increased mortality. Depression and anxiety have been widely reported soon after coronary artery bypass surgery and remain evident one year after surgery. They may increase the likelihood for new coronary artery events, further hospitalizations and increased mortality. Morbidly obese patients who undergo bariatric surgery have an increased risk of depression. Postoperative depression may also be associated with less weight loss at one year and longer. The extent of preoperative depression in patients scheduled for lumbar discectomy is a predictor of functional outcome and patient's dissatisfaction, especially after revision surgery. General postoperative mortality is increased. CONCLUSIONS: Depression is a frequent cause of morbidity in surgery patients suffering from a wide range of conditions. Depression may be identified through the use of Patient Health Questionnaire-9 or similar instruments. Counseling interventions may be useful in ameliorating depression, but should be subject to clinical trials. PMID- 26830196 TI - Probiotic (Enterococcus faecium) induced responses of the hepatic proteome improves metabolic efficiency of broiler chickens (Gallus gallus). AB - BACKGROUND: The liver plays important roles in nutrient metabolism, detoxification and immunity. Enterococcus faecium (E. faecium) is a probiotic that has been shown to have positive effects on broiler production. However, its molecular effects on liver metabolism have not been characterized. This study aims to further identify the biological roles of E. faecium by characterizing the hepatic proteomic changes of broilers (Gallus gallus) fed E. faecium using two dimensional fluorescence difference gel electrophoresis (2-D DIGE) and mass spectrometry (MS). RESULTS: Thirty-three proteins (50 protein spots) involved in nutrient metabolism, immunity and the antioxidant system were shown to be differentially expressed in the liver of broilers fed E. faecium than from birds not fed the probiotic. The biological processes of sulphur amino acids, vitamin and cellular hormone metabolism, sulphur compound biosynthesis and protein tetramerization were enhanced in the liver of broilers fed E. faecium. However, proteins involved in calcium ion flux, cell redox homeostasis and platelet activation related to hepatic immune responses were down-regulated in broilers fed E. faecium. These results indicate that the supplementation of poultry feed with E. faecium may alter the partitioning of nutrients and promote optimal nutrient utilization. CONCLUSIONS: This study assists in unraveling the molecular effects of the dietary probiotic, E. faecium, in the liver of broiler chickens. It shows that the probiotic improves the metabolism of nutrients and decreases inflammatory responses. Our findings extend previous knowledge of the mechanism of dietary probiotic action and provide new findings for research and future probiotic development. PMID- 26830197 TI - Effects of a home-based intervention on diet and physical activity behaviours for rural adults with or at risk of metabolic syndrome: a randomised controlled trial. AB - BACKGROUND: This study aimed to determine whether a home-based 6-month lifestyle intervention program complemented by motivational interviewing could improve diet and physical activity behaviours in 50-69 year olds with or at risk of metabolic syndrome, residing in a disadvantaged rural Western Australian community. METHODS: Participants from the City of Albany and surrounding towns (n = 401) were recruited into a 6 month randomised controlled trial. They were screened for metabolic syndrome and randomly allocated to intervention (n = 201) or control group (n = 200). Baseline and post-test data collection for both groups included a self-report questionnaire which incorporated the Fat and Fibre Barometer and the International Physical Activity Questionnaire Short Form. The intervention group received the program materials at baseline and the control group was waitlisted. Generalised estimating equation models assessed repeated outcome measures over time. RESULTS: A total of 151 (75.1%) intervention and 159 (79.5%) control group participants completed post-test and were included in the analysis. After controlling for confounders, the intervention group achieved a marginally significant increase in their metabolic equivalent (MET) minutes of moderate intensity physical activity per week (p = 0.049), and significantly improved fibre intake (p < 0.001), fat intake (p = 0.003), and vegetable serves per day (p = 0.002) from baseline to post-test relative to the control group. CONCLUSION: A home-based, low-cost intervention with motivational support can effectively improve the physical activity and dietary behaviours of adults aged 50-69 years with or at risk of metabolic syndrome residing in a disadvantaged rural area. TRIAL REGISTRATION: Anzctr.org.au Identifier: ACTRN12614000512628. PMID- 26830199 TI - Two Equilibria of (N-Methyl-3-pyridinium)chlorocarbene, a Cationic Carbene. AB - Equilibrium constants and the associated thermodynamic parameters are reported for the equilibria established between the cationic carbene (N-methyl-3 pyridinium)chlorocarbene tetrafluoroborate (MePyr(+)CCl BF4(-), 3) and 1,3,5 trimethoxybenzene (TMB) to form a carbene-TMB complex, as well as between carbene 3 and chloride ion to form the zwitterion, N-methyl-3-pyridinium dichloromethide (10). These equilibrium constants and thermodynamic parameters are contrasted with analogous data for several related carbenes, and the influence of the pyridinium unit in carbene 3 is thereby highlighted. Computational studies augment and elucidate the experimental results. PMID- 26830198 TI - LOng-term follow-up after liVE kidney donation (LOVE) study: a longitudinal comparison study protocol. AB - BACKGROUND: The benefits of live donor kidney transplantation must be balanced against the potential harm to the donor. Well-designed prospective studies are needed to study the long-term consequences of kidney donation. METHODS: The "LOng term follow-up after liVE kidney donation" (LOVE) study is a single center longitudinal cohort study on long-term consequences after living kidney donation. We will study individuals who have donated a kidney from 1981 through 2010 in the Erasmus University Medical Center in Rotterdam, The Netherlands. In this time period, 1092 individuals donated a kidney and contact information is available for all individuals. Each participating donor will be matched (1:4) to non-donors derived from the population-based cohort studies of the Rotterdam Study and the Study of Health in Pomerania. Matching will be based on baseline age, gender, BMI, ethnicity, kidney function, blood pressure, pre-existing co-morbidity, smoking, the use of alcohol and highest education degree. Follow-up data is collected on kidney function, kidney-related comorbidity, mortality, quality of life and psychological outcomes in all participants. DISCUSSION: This study will provide evidence on the long-term consequences of live kidney donation for the donor compared to matched non-donors and evaluate the current donor eligibility criteria. TRIAL REGISTRATION: Dutch Trial Register NTR3795 . PMID- 26830200 TI - HMGB1Modulates the Treg/Th17 Ratio in Atherosclerotic Patients. AB - AIM: Atherosclerosis (AS) characterized as a chronic inflammatory disease. Multiple immune cells and inflammatory cytokines, such as high mobility group protein (HMGB1), regulatory T (Treg) cells, T helper (Th17) cells, and inflammation-related cytokines, play a key role in its pathophysiology. A large number of studies report that HMGB1 and Th17 cells may promote atherosclerosis progression, whereas Treg cells may play a protective role in atherosclerosis; thus, alterations in the Treg/Th17 ratio may exist in atherosclerosis diseases. Up till now, the relationships between HMGB1 levels and the Treg/Th17 ratio remain incompletely understood. The major purpose of this study was to investigate the relationship between HMGB1 levels and the Treg/Th17 ratio in patients with coronary artery atherosclerotic plaques. METHODS: We enrolled patients with coronary atherosclerosis and normal coronary artery as the research subjects. Flow cytometry was used to analyze the Treg cells, the Th17 cells frequency, and the Treg/Th17 ratio. Otherwise, real-time polymerase chain reaction was used for assays the mRNA expressions of HMGB1, retinoic acid-related orphan nuclear receptor C (RORC), and forkhead-winged helix transcription factor (Foxp3). Moreover, enzyme-linked immunosorbent assays were used to detect the level of protein and cytokines, such as HMGB1, IL-10, TGF-beta1, IL-17A, and IL 23. RESULTS: Using flow cytometry, we observed a significantly increased of Th17 cell frequency, whereas Treg cell frequency significantly decreased in atherosclerotic patients. Consistently, the levels of RORC mRNA were significantly increased in coronary atherosclerosis (AS) group compared to normal coronary artery (NCA) group (P<0.01). In contrast, the expression of Foxp3 mRNA was markedly lower in the AS group than in the NCA group (P<0.01). Furthermore, we observed the serum concentrations of HMGB1, IL-17A, and IL-23 were significantly higher in the AS group than in the NCA group (P<0.01, respectively), whereas the concentrations of serum IL-10 and TGF-beta1 were significantly lower in the AS group than in the NCA group (P<0.01, respectively). In addition, we also found that HMGB1 levels showed negative correlation with the Treg/Th17 ratio in the two groups (r=-0.6984, P<0.01). CONCLUSIONS: The data in our study indicated that HMGB1 may promote atherosclerosis progression via modulating the imbalance in the Treg/Th17 ratio. PMID- 26830201 TI - High-Density Lipoprotein Mimetics: a Therapeutic Tool for Atherosclerotic Diseases. AB - Clinical trials and epidemiological studies have revealed a negative correlation between serum high-density lipoprotein (HDL) cholesterol levels and the risk of cardiovascular events. Currently, statin treatment is the standard therapy for cardiovascular diseases, reducing plasma low-density lipoprotein (LDL) cholesterol levels. However, more than half of the patients have not been able to receive the beneficial effects of this treatment.The reverse cholesterol transport pathway has several potential anti-atherogenic properties. An important approach to HDL-targeted therapy is the optimization of HDL cholesterol levels and function in the blood to enhance the removal of circulating cholesterol and to prevent or mitigate inflammation that causes atherosclerosis. Cholesteryl ester transfer protein inhibitors increase HDL cholesterol levels in humans, but whether they reduce the risk of atherosclerotic diseases is unknown. HDL therapies using HDL mimetics, including reconstituted HDL, apolipoprotein (Apo) A IMilano, ApoA-I mimetic peptides, or full-length ApoA-I, are highly effective in animal models. In particular, the Fukuoka University ApoA-I-mimetic peptide (FAMP) effectively removes cholesterol via the ABCA1 transporter and acts as an anti-atherosclerotic agent by enhancing the biological functions of HDL without elevating HDL cholesterol levels.Our literature review suggests that HDL mimetics have significant atheroprotective potential and are a therapeutic tool for atherosclerotic diseases. PMID- 26830202 TI - In Search of an Optimal Target Level of Low Density Lipoprotein Cholesterol for Secondary Prevention Among the Japanese Population. PMID- 26830203 TI - Distribution of Angiostrongylus vasorum and its gastropod intermediate hosts along the rural-urban gradient in two cities in the United Kingdom, using real time PCR. AB - BACKGROUND: Angiostrongylus vasorum is a highly pathogenic metastrongylid nematode affecting dogs, which uses gastropod molluscs as intermediate hosts. The geographical distribution of the parasite appears to be heterogeneous or patchy and understanding of the factors underlying this heterogeneity is limited. In this study, we compared the species of gastropod present and the prevalence of A. vasorum along a rural-urban gradient in two cities in the south-west United Kingdom. METHODS: The study was conducted in Swansea in south Wales (a known endemic hotspot for A. vasorum) and Bristol in south-west England (where reported cases are rare). In each location, slugs were sampled from nine sites across three broad habitat types (urban, suburban and rural). A total of 180 slugs were collected in Swansea in autumn 2012 and 338 in Bristol in summer 2014. A 10 mg sample of foot tissue was tested for the presence of A. vasorum by amplification of the second internal transcribed spacer (ITS-2) using a previously validated real-time PCR assay. RESULTS: There was a significant difference in the prevalence of A. vasorum in slugs between cities: 29.4% in Swansea and 0.3% in Bristol. In Swansea, prevalence was higher in suburban than in rural and urban areas. Comparing the sampled slug fauna, Arion rufus was found in greater numbers in Swansea than Bristol, and was commonly infected (prevalence 41%). This, alongside the timing of slug collections in summer rather than autumn, could explain low infection prevalence in the Bristol sample. In the absence of Ar. rufus as a preferred host for A. vasorum, Ar. flagellus and Limacus maculatus appear to act as versatile hosts that are present in suburban and urban areas in Swansea (prevalence in Ar. flagellus 33%; in L. maculatus 44%) and in Bristol (prevalence in Ar. flagellus 0.9%). These slug species might provide A. vasorum with an alternative vehicle to reach the final host, when the main host Ar. rufus is scarce or absent. CONCLUSION: We conclude that the composition of the slug fauna varies spatially, and that this could help explain patchiness in the prevalence of A. vasorum. A suburban peak was found in the prevalence of infection in intermediate hosts, perhaps explained by a higher density of competent intermediate and/or definitive hosts. PMID- 26830204 TI - Understanding the Association Between Chronic Obstructive Pulmonary Disease and Current Anxiety: A Population-Based Study. AB - This study's objectives were to investigate the independent relationship between COPD and past-year Generalized Anxiety Disorder (GAD) in a population-based sample of adult Canadians and to identify significant correlates of GAD among COPD patients. A series of logistic regression analyses were conducted with a sample of 11,163 respondents aged 50+ from the 2012 Canadian Community Health Survey-Mental Health to determine the degree to which the direct association between COPD and GAD was attenuated by socio-demographic factors, social support, health behaviors, sleep problems, pain, functional limitations, and early childhood adversities. Additional analyses were completed using the sub-sample of those diagnosed with COPD (n = 746) to determine predictors of GAD. One in 17 (5.8%) of older individuals with COPD had past-year GAD, in comparison to 1.7% of those without (p < .001). The age-sex-race adjusted odds of GAD were four times higher for those with COPD compared to those without COPD (OR = 3.90, 95%CI: 2.64, 5.77). After full adjustment for 18 characteristics, these odds declined to 1.72 (95%CI: 1.10, 2.71). Factors associated with GAD among those with COPD include not having a confidant (OR = 7.85, 95%CI: 3.47, 17.75), exposure to parental domestic violence (OR = 5.63, 95% CI: 2.07, 15.34) and lifetime depressive disorders (OR = 3.59, 95% CI:1.61,7.98). Those with COPD have substantially higher odds of GAD even after most known risk factors for GAD are accounted for. These findings have implications for targeted outreach and screening, particularly for patients with pain and functional limitations. The importance of a multidisciplinary healthcare team is underscored by the multiple issues that may impact GAD among COPD patients. PMID- 26830205 TI - The Epidemic Dynamics of Four Major Lineages of HIV-1 CRF01_AE Strains After Their Introduction into China. AB - The epidemic of HIV-1 CRF01_AE in China was driven by multiple lineages of HIV-1 viruses introduced in the 1990s and increasing; it is important to investigate their epidemic status in China. In this study, we download all available CRF01_AE sequences (n = 2,931) from China and their associated epidemiological information in the Los Alamos HIV database for our analysis to explore their epidemic status in China. The results showed there were 11 distinct clusters of CRF01_AE strains in China, and 4 major clusters that accounted for 80.0% (1,793/2,241) of Chinese CRF01_AE strains in total had led a real epidemic. Clusters 1 and 2 were epidemic among heterosexuals and injecting drug users in southern and southwestern China, while Clusters 3 and 4 were predominant among homosexuals in eastern and central China and northeastern China, respectively. HIV-1 CRF01_AE strains detected in heterosexuals had the most complex characteristic, underscoring its important role in the occurrence of multiple CRF01_AE lineages. Furthermore, epidemic history reconstruction analysis using the birth-death susceptible-infected removed package revealed that the four clusters had gone through varying epidemic stages. Clusters 2 and 3 were near the peak of the local epidemic, while Clusters 1 and 4 were just in the very early stage of their epidemic. The epidemic status of CRF01_AE clusters in the future is mainly determined by the effect of prevention and control. Our study provides new insights into the understanding of the epidemic dynamics of CRF01_AE in China. PMID- 26830206 TI - Integrative functional transcriptomic analyses implicate specific molecular pathways in pulmonary toxicity from exposure to aluminum oxide nanoparticles. AB - Gene expression profiling has developed rapidly in recent years and it can predict and define mechanisms underlying chemical toxicity. Here, RNA microarray and computational technology were used to show that aluminum oxide nanoparticles (Al2O3 NPs) were capable of triggering up-regulation of genes related to the cell cycle and cell death in a human A549 lung adenocarcinoma cell line. Gene expression levels were validated in Al2O3 NPs exposed A549 cells and mice lung tissues, most of which showed consistent trends in regulation. Gene-transcription factor network analysis coupled with cell- and animal-based assays demonstrated that the genes encoding PTPN6, RTN4, BAX and IER play a role in the biological responses induced by the nanoparticle exposure, which caused cell death and cell cycle arrest in the G2/S phase. Further, down-regulated PTPN6 expression demonstrated a core role in the network, thus expression level of PTPN6 was rescued by plasmid transfection, which showed ameliorative effects of A549 cells against cell death and cell cycle arrest. These results demonstrate the feasibility of using gene expression profiling to predict cellular responses induced by nanomaterials, which could be used to develop a comprehensive knowledge of nanotoxicity. PMID- 26830207 TI - Promoting Endochondral Bone Repair Using Human Osteoarthritic Articular Chondrocytes. AB - INTRODUCTION: Current tissue engineering strategies to heal critical-size bone defects through direct bone formation are limited by incomplete integration of grafts with host bone and incomplete graft vascularization. An alternative strategy for bone regeneration is the use of cartilage grafts that form bone through endochondral ossification. Endochondral cartilages stimulate angiogenesis and are remodeled into bone, but are found in very small quantities in growth plates and healing fractures. We sought to develop engineered endochondral cartilage grafts using osteoarthritic (OA) articular chondrocytes as a cell source. Such chondrocytes often undergo hypertrophy, which is a characteristic of endochondral cartilages. MATERIALS AND METHODS: We compared the ability of unmodified human OA (hOA) cartilage and cartilage grafts formed in vitro from hOA chondrocytes to undergo endochondral ossification in mice. Scaffold-free engineered chondrocyte grafts were generated by pelleting chondrocytes, followed by culture with transforming growth factor-beta1 (TGF-beta1) and bone morphogenetic protein 4. Samples derived from either primary or passaged chondrocytes were implanted subcutaneously into immunocompromised mice. Grafts derived from passaged chondrocytes from three patients were implanted into critical-size tibial defects in mice. Bone formation was assessed with histology after 4 weeks of implantation. The composition of tibial repair tissue was quantified with histomorphometry. RESULTS: Engineered cartilage grafts generated from passaged OA chondrocytes underwent endochondral ossification after implantation either subcutaneously or in bone. Cartilage grafts integrated with host bone at 15 out of 16 junctions. Grafts variably remodeled into woven bone, with the proportion of bony repair tissue in tibial defects ranging from 22% to 85% (average 48%). Bony repair tissue bridged the tibial defects in half of the animals. In contrast, unmodified OA cartilage and engineered grafts formed from primary chondrocytes did not undergo endochondral ossification in vivo. CONCLUSIONS: hOA chondrocytes can adopt an endochondral phenotype after passaging and TGF-beta superfamily treatment. Engineered endochondral cartilage grafts can integrate with host bone, undergo ossification, and heal critical-size long-bone defects in a mouse model. However, additional methods to further enhance ossification of these grafts are required before the clinical translation of this approach. PMID- 26830208 TI - Genomic prediction of breeding values for carcass traits in Nellore cattle. AB - BACKGROUND: The objective of this study was to evaluate the accuracy of genomic predictions for rib eye area (REA), backfat thickness (BFT), and hot carcass weight (HCW) in Nellore beef cattle from Brazilian commercial herds using different prediction models. METHODS: Phenotypic data from 1756 Nellore steers from ten commercial herds in Brazil were used. Animals were offspring of 294 sires and 1546 dams, reared on pasture, feedlot finished, and slaughtered at approximately 2 years of age. All animals were genotyped using a 777k Illumina Bovine HD SNP chip. Accuracy of genomic predictions of breeding values was evaluated by using a 5-fold cross-validation scheme and considering three models: Bayesian ridge regression (BRR), Bayes C (BC) and Bayesian Lasso (BL), and two types of response variables: traditional estimated breeding value (EBV), and phenotype adjusted for fixed effects (Y*). RESULTS: The prediction accuracies achieved with the BRR model were equal to 0.25 (BFT), 0.33 (HCW) and 0.36 (REA) when EBV was used as response variable, and 0.21 (BFT), 0.37 (HCW) and 0.46 (REA) when using Y*. Results obtained with the BC and BL models were similar. Accuracies increased for traits with a higher heritability, and using Y* instead of EBV as response variable resulted in higher accuracy when heritability was higher. CONCLUSIONS: Our results indicate that the accuracy of genomic prediction of carcass traits in Nellore cattle is moderate to high. Prediction of genomic breeding values from adjusted phenotypes Y* was more accurate than from EBV, especially for highly heritable traits. The three models considered (BRR, BC and BL) led to similar predictive abilities and, thus, either one could be used to implement genomic prediction for carcass traits in Nellore cattle. PMID- 26830209 TI - 3D-QSAR Studies on the Biological Activity of Imidazolidinylpiperidinylbenzoic Acids as Chemokine Receptor Antagonists. AB - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) infection ultimately leading to acquired immunodeficiency syndrome (AIDS), remains a significant problem. CCR5 is a member of the chemokine receptor family that is utilized in the early stage of the replication cycle by the most commonly transmitted M tropic strains of HIV-1. In this study, we developed 3D-QSAR models using CoMFA and CoMSIA methods on a series of 71 imidazolidinylpiperidinylbenzoic acid CCR5 antagonists, in order to better understand the substituent requirements and get more potent antagonists of CCR5. METHODS: The research of 3D-QSAR modeling of imidazolidinylpiperidinylbenzoic acids as chemokine receptor 5 (CCR5) antagonists was conducted using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). RESULTS: For this study, a dataset containing 71 imidazolidinyl-piperidinyl-benzoic acids was divided into a training set of 22 compounds and a test set of 49 compounds. The results obtained from the CoMFA/CoMSIA model exhibited a statistical significance r(2) of 0.996 (0.984) with an estimated standard error of 0.109 (0.209). CONCLUSION: Both CoMFA and CoMSIA models provided valuable insight into the structural requirements for improving the activity of then CCR5 antagonists. PMID- 26830210 TI - Perpetuation of torsade de pointes in heterogeneous hearts: competing foci or re entry? AB - KEY POINTS: The underlying mechanism of torsade de pointes (TdP) remains of debate: perpetuation may be due to (1) focal activity or (2) re-entrant activity. The onset of TdP correlates with action potential heterogeneities in different regions of the heart. We studied the mechanism of perpetuation of TdP in silico using a 2D model of human cardiac tissue and an anatomically accurate model of the ventricles of the human heart. We found that the mechanism of perpetuation TdP depends on the degree of heterogeneity. If the degree of heterogeneity is large, focal activity alone can sustain a TdP, otherwise re-entrant activity emerges. This result can help to understand the relationship between the mechanisms of TdP and tissue properties and may help in developing new drugs against it. ABSTRACT: Torsade de pointes (TdP) can be the consequence of cardiac remodelling, drug effects or a combination of both. The mechanism underlying TdP is unclear, and may involve triggered focal activity or re-entry. Recent work by our group has indicated that both cases may exist, i.e. TdPs induced in the chronic atrioventricular block (CAVB) dog model may have a focal origin or are due to re-entry. Also it was found that heterogeneities might play an important role. In the current study we have used computational modelling to further investigate the mechanisms involved in TdP initiation and perpetuation, especially in the CAVB dog model, by the addition of heterogeneities with reduced repolarization reserve in comparison with the surrounding tissue. For this, the TNNP computer model was used for computations. We demonstrated in 2D and 3D simulations that ECGs with the typical TdP morphology can be caused by both multiple competing foci and re-entry circuits as a result of introduction of heterogeneities, depending on whether the heterogeneities have a large or a smaller reduced repolarization reserve in comparison with the surrounding tissue. Large heterogeneities can produce ectopic TdP, while smaller heterogeneities will produce re-entry-type TdP. PMID- 26830211 TI - The role of targeted treatment in mantle cell lymphoma: is transplant dead or alive? AB - Based on the profound biological insights of the last years into the molecular pathogenesis of mantle cell lymphoma and the clinical introduction of new targeted drugs, with high efficacy and a good safety profile, the therapeutic scenario for this tumor has been shown to be thoroughly favourable. No longer characterized by a uniformly dismal prognosis, mantle cell lymphoma has been revealed as a spectrum of different diseases, ranging from very indolent cases to highly aggressive and refractory ones. Thus, there is an urgent need to adapt therapy to accommodate the diverse presentations of the disease. High-dose chemotherapy, followed by autologous stem cell transplantation is the current standard of care for younger patients, generally providing high responses and long survival rates, but hampered by acute and long-term toxicity. In addition, some patients may be overtreated, while others could benefit from targeted approaches, based on the new, molecular-directed compounds. Such a personalized treatment based on the specific characteristics of individual patients may be guided by validated prognostic tools, such as the Mantle Cell Lymphoma International Prognostic Index and the Ki-67 Proliferative Index, as well as by early predictors of treatment response, like minimal residual disease analysis. Moreover, mutation screening of distinctive genomic alterations may provide new, predictive biomarkers, with an additional impact on clinical practice. Only after tailoring treatment according to the clinical and biological heterogeneity of the disease the role of transplantation and modern therapeutic options will be redefined in mantle cell lymphoma. PMID- 26830213 TI - Fluid management in the critically ill: science or invention? PMID- 26830212 TI - Iron deficiency anemia in cyclic GMP kinase knockout mice. PMID- 26830214 TI - Intraoperative factors associated with delayed recovery of liver function after hepatectomy: analysis of 1969 living donors. AB - BACKGROUND: The safety of healthy living donors who are undergoing hepatic resection is a primary concern. We aimed to identify intraoperative anaesthetic and surgical factors associated with delayed recovery of liver function after hepatectomy in living donors. METHODS: We retrospectively analysed 1969 living donors who underwent hepatectomy for living donor liver transplantation. Delayed recovery of hepatic function was defined by increases in international normalised ratio of prothrombin time and concomitant hyperbilirubinaemia on or after post operative day 5. Univariate and multivariate logistic regression analyses were performed to determine the factors associated with delayed recovery of hepatic function after living donor hepatectomy. RESULTS: Delayed recovery of liver function after donor hepatectomy was observed in 213 (10.8%) donors. Univariate logistic regression analysis showed that sevoflurane anaesthesia, synthetic colloid, donor age, body mass index, fatty change and remnant liver volume were significant factors for prediction of delayed recovery of hepatic function. Multivariate logistic regression analysis showed that independent factors significantly associated with delayed recovery of liver function after donor hepatectomy were sevoflurane anaesthesia (odds ratio = 3.514, P < 0.001), synthetic colloid (odds ratio = 1.045, P = 0.033), donor age (odds ratio = 0.970, P = 0.003), female gender (odds ratio = 1.512, P = 0.014) and remnant liver volume (odds ratio = 0.963, P < 0.001). CONCLUSIONS: Anaesthesia with sevoflurane was an independent factor in predicting delayed recovery of hepatic function after donor hepatectomy. Although synthetic colloid may be associated with delayed recovery of hepatic function after donor hepatectomy, further study is required. These results can provide useful information on perioperative management of living liver donors. PMID- 26830215 TI - Pharmacokinetics and pharmacodynamics of piperacillin/tazobactam during high volume haemodiafiltration in patients with septic shock. AB - BACKGROUND: The purpose of the study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of piperacillin and tazobactam during high-volume haemodiafiltration (HVHDF). METHODS: A single dose of piperacillin/tazobactam (4/0.5 g) was administered as 30 minute infusion during HVHDF to 10 patients with acute kidney injury due to septic shock. Arterial blood samples were collected before and at 30 or 60 min intervals over 8 h (12 samples) after study drug administration. Concentrations of piperacillin and tazobactam were determined by HPLC-MS/MS. R software was used for population PK analysis and Monte Carlo Simulation of probability of PK/PD target attainment (PTA) in 1000 subjects. RESULTS: A total of 101 samples were collected during HVHDF. The median (IQR) estimated glomerular filtration rate of the patients was 16 (11.25-27.5) ml/min/1.73 m(2) and HVHDF effluent rate was 208 (146.3-298.3) ml/kg/h. A final two-compartment population PK model predicted mean (%SE) total piperacillin clearance on HVHDF was 6.9 (6.4) l/h, volume of distribution of central compartment 9.0 (10.1) l and of peripheral compartment 11.2 (12.2) l. The PTA of 50% fT>MIC for piperacillin 4 g/tazobactam 0.5 g dosed every 8 h as 0.5-h and 4-h infusion was 84.3% and 100% for MIC of 16 mg/l respectively. Aiming 100% fT>MIC of 16 mg/l, the PTA values were 88.6% and 61.0%, for piperacillin 4 g/tazobactam 0.5 g 4-h infusion every 6 and 8 h respectively. CONCLUSIONS: For bactericidal PK/PD target attainment piperacillin/tazobactam doses of 4/0.5 g every 8 h appear appropriate in septic shock patients with minimal residual renal function during HVHDF. PMID- 26830216 TI - Artemisinin protects mice against burn sepsis through inhibiting NLRP3 inflammasome activation. AB - BACKGROUND: NLRP3 inflammasome activation is recently reported to be linked to the pathogenesis of sepsis. Artemisinin is shown to play beneficial effects in sepsis. However, the impacts of artemisinin on burn sepsis have not been investigated. This study is designed to investigate the role of artemisinin in burn sepsis and the involvement of NLRP3 inflammasome activation. METHODS: Male BALB/c mice were randomly divided into sham burn, burn, burn sepsis, and artemisinin treated groups. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Adhesion molecules and neutrophil infiltration in lung and heart were detected by real-time polymerase chain reaction. Mortality rates were monitored. Artemisinin was added to Raw 264.7 cells that were stimulated with burn sepsis serum in the presence/absence of an inhibitor of NLRP3 inflammasome, 3, 4-methylenedioxy-beta-nitrostyrene. Interleukin (IL) 1beta and IL-18 messenger RNA expression as well as NLRP3 and caspase 1 protein were measured. RESULTS: Production of inflammatory cytokines in serum, levels of adhesion molecules and neutrophil infiltration in lung and heart, and mortality rate of burn septic mice were significantly higher than those of control. These effects were attenuated by artemisinin. Artemisinin down-regulated protein levels of NLRP3 and caspase 1 and inhibited the increases of IL-1beta and IL-18 messenger RNA expression from Raw 264.7 cells that were stimulated with burn sepsis serum. These effects of artemisinin were not further strengthened in the presence of 4-methylenedioxy beta-nitrostyrene. CONCLUSION: Artemisinin protects mice from burn sepsis by attenuating the inflammatory response and alleviating inflammatory infiltration in vital organs, likely through inhibiting the activation of NLRP3 inflammasome. PMID- 26830217 TI - Treatment of septic hip in a pediatric ED: a retrospective case series analysis. AB - BACKGROUND: A pediatric septic hip is a serious condition that must be recognized and treated as early as possible. We describe the clinical course of children with septic hip that were treated with aspiration of the hip joint in the emergency department (AHED). METHODS: This was a retrospective case series analysis. RESULTS: Between January 1, 2007, and December 31, 2014, 17 children with septic hip were diagnosed by emergency physicians using point-of-care ultrasonography. All were treated with AHED. During hospital admission, a median of 2 (interquartile range [IQR], 2-3) follow-up sonographic examinations per patient was performed; 10 (59%) patients did not have another hip aspiration, and 7 (41%) had a median of 1 (IQR, 1-3) hip joint aspiration under sedation. Median length of antibiotic treatment was 28 days (IQR, 21-40). No patient underwent arthrotomy, and all recovered without disability in up to 4 years of follow-up. CONCLUSIONS: The results of this cohort suggest that AHED with repeated aspirations as needed is an effective treatment for children with septic hip. PMID- 26830218 TI - Effects of long axis in-plane vs short axis out-of-plane techniques during ultrasound-guided vascular access. AB - BACKGROUND: Currently, whether long-axis in-plane (LA-IP) is superior to short axis out-of-plane (SA-OOP) during ultrasound-guided vascular access remains inconclusive. We, therefore, conducted a meta-analysis of randomized controlled trials to compare the effects of LA-IP vs SA-OOP techniques in patients undergoing ultrasound-guided vascular access (USGVA). METHODS: A computer-based literature search of PubMed, Embase, and the Cochrane Library (up to October 2015) was performed to identify randomized controlled trials that evaluated the effects of LA-IP compared with SA-OOP in patients undergoing USGVA. The primary end point was the first-pass success rate. Secondary end points included mean time to success, mean attempts to success, and incidence of the complication of hematoma. Weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs) were calculated by random-effects model. RESULTS: Five eligible studies with a total of 470 patients satisfied the inclusion criteria. There was no significant difference for the first-pass success rate (RR, 1.06; 95% CI, 0.91-1.23; P = .44), mean time to success (WMD, 4.78seconds; 95% CI, 4.43 to 13.99; P = .31), mean attempts to success (WMD, 0.06 times; 95% CI, -0.23 to 0.35; P = .69), and incidence of the complication of hematoma (RR, 2.86; 95% CI, 0.32-25.42; P = .35) between the LA-IP and SA-OOP groups. CONCLUSIONS: There is insufficient evidence to definitively choose either LA-IP or SA-OOP in patients undergoing USGVA. Further robustly well-designed trials are warranted to investigate the appropriate technique in patients receiving USGVA. PMID- 26830219 TI - beta Agonist-induced lactic acidosis, an evidence-based approach to a critical question. PMID- 26830220 TI - Sling and swathe modification for immobilization of posterior glenohumeral dislocations. PMID- 26830221 TI - Effectiveness of Prevention Strategies for Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis. AB - BACKGROUND: N-acetylcysteine, sodium bicarbonate, statins, and ascorbic acid have been studied for reducing contrast-induced nephropathy (CIN). PURPOSE: To evaluate the comparative effectiveness of interventions to reduce CIN in adults receiving contrast media. DATA SOURCES: MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and Scopus databases through June 2015. Risk of bias and overall strength of evidence (SOE) of studies were assessed. STUDY SELECTION: Randomized, controlled trials of N-acetylcysteine, sodium bicarbonate, statins, or ascorbic acid that used intravenous (IV) or intra-arterial contrast media and defined CIN with enough data for meta-analysis. DATA EXTRACTION: Two reviewers independently extracted data and assessed study quality. DATA SYNTHESIS: Low-dose N-acetylcysteine plus IV saline compared with IV saline (risk ratio [RR], 0.75 [95% CI, 0.63 to 0.89]; low SOE), N-acetylcysteine plus IV saline compared with IV saline in patients receiving low-osmolar contrast media (RR, 0.69 [CI, 0.58 to 0.84]; moderate SOE), and statins plus N-acetylcysteine plus IV saline versus N acetylcysteine plus IV saline (RR, 0.52 [CI, 0.29 to 0.93]; low SOE) had clinically important and statistically significant benefits. The following 3 comparisons suggested a clinically important difference that was not statistically significant: sodium bicarbonate versus IV saline in patients receiving low-osmolar contrast media (RR, 0.65 [CI, 0.33 to 1.25]; low SOE), statins plus IV saline versus IV saline (RR, 0.68 [CI, 0.39 to 1.20]; low SOE), and ascorbic acid versus IV saline (RR, 0.72 [CI, 0.48 to 1.01]; low SOE). Strength of evidence was generally insufficient for comparisons of the need for renal replacement, cardiac events, and mortality. LIMITATION: Too few studies were done in patients receiving IV contrast media. CONCLUSION: The greatest reduction in CIN was seen with N-acetylcysteine plus IV saline in patients receiving LOCM and with statins plus N-acetylcysteine plus IV saline. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. PMID- 26830222 TI - Prosthesis-Patient Mismatch After Transcatheter Aortic Valve Implantation. AB - BACKGROUND: We reviewed currently available studies that investigated prosthesis patient mismatch (PPM) in transcatheter aortic valve implantation (TAVI) with a systematic literature search and meta-analytic estimates. METHODS: To identify all studies that investigated PPM in TAVI, MEDLINE and EMBASE were searched through August 2015. Studies considered for inclusion met the following criteria: the study population included patients undergoing TAVI and outcomes included at least post-procedural PPM prevalence. We performed three quantitative meta analyses about (1) PPM prevalence after TAVI, (2) PPM prevalence after TAVI versus surgical aortic valve replacement (SAVR), and (3) late all-cause mortality after TAVI in patients with PPM versus patients without PPM. RESULTS: We identified 21 eligible studies that included data on a total of 4,000 patients undergoing TAVI. The first meta-analyses found moderate PPM prevalence of 26.7%, severe PPM prevalence of 8.0%, and overall PPM prevalence of 35.1%. The second meta-analyses of six studies, including 745 patients, found statistically significant reductions in moderate (p = 0.03), severe (p = 0.0003), and overall (p = 0.02) PPM prevalence after TAVI relative to SAVR. The third meta-analyses of five studies, including 2,654 patients, found no statistically significant differences in late mortality between patients with severe PPM and patients without PPM (p = 0.44) and between patients with overall PPM and patients without PPM (p = 0.97). CONCLUSIONS: Overall, moderate, and severe PPM prevalence after TAVI was 35%, 27%, and 8%, respectively, which may be less than that after SAVR. In contrast to PPM after SAVR, PPM after TAVI may not impair late survival. PMID- 26830223 TI - Surgical Treatment of Renal Cell Carcinoma With Cavoatrial Involvement: A Systematic Review of the Literature. AB - The treatment of renal cell carcinoma (RCC) with cavoatrial involvement represents a major surgical challenge. To date, many surgical strategies have been proposed. However, general agreement on the best approach does not yet exist. Deep hypothermic circulatory arrest (DHCA) is the most commonly used method and allows complete tumor resection without increasing operative risk. Cardiopulmonary bypass (CPB) without circulatory arrest and methods using no CBP were also proposed, without a clear evidence of superiority of 1 technique over the others. Further studies are needed to evaluate the possible role of alternative techniques compared with deep hypothermic circulatory arrest. PMID- 26830224 TI - Aggressive Patch Augmentation May Reduce Growth Potential of Hypoplastic Branch Pulmonary Arteries After Tetralogy of Fallot Repair. AB - BACKGROUND: Potential surgical strategies for hypoplastic branch pulmonary arteries (BPAs) during tetralogy of Fallot repair include (1) extensive patch augmentation to the hilum (PATCH), (2) limited extension arterioplasty to the proximal pulmonary artery (EXTENSION), or (3) leaving the native vessels unaugmented (NATIVE). We explored the effect of these strategies on reintervention and BPA growth. METHODS: From 2000 to 2012, 434 children underwent complete tetralogy of Fallot repair. Risk-adjusted parametric models were used to analyze the risk of BPA reintervention for (1) all children, (2) children with BPAs of 4 mm or smaller, and (3) children with BPAs of 3 mm or smaller. Repeated measures analysis of more than 2,000 echocardiograms was used to characterize postoperative BPA growth and right ventricular pressure by using nonlinear mixed models. RESULTS: Overall survival (99% [3 deaths]) was excellent. The 10-year freedom from BPA reintervention was 84%. In risk-adjusted models (including baseline BPA z-score), PATCH had a decreased freedom from reintervention (73%; p < 0.01) vs EXTENSION (87%) or NATIVE (91%). For children with BPAs of 4 mm or smaller (28 PATCH, 60 EXTENSION, 75 NATIVE), baseline characteristics were similar. The risk-adjusted 5-year freedom from reintervention was 68% for PATCH, 76% for EXTENSION, and 85% for NATIVE. PATCH trended toward an increased risk of reintervention (p = 0.07). For children with BPAs of 4 mm or smaller left in their NATIVE state, only ~15% required reintervention. After adjustment for baseline BPA z-score, the time-related BPA growth was decreased (p < 0.014) and right ventricular pressure was increased (p = 0.03) for the PATCH group. CONCLUSIONS: Aggressive PATCH augmentation of hypoplastic BPAs improves the short term geometry but may lead to late stenosis and higher rates of reintervention. Hypoplastic BPAs in tetralogy of Fallot tend (~85%) to grow well without instrumentation. PMID- 26830225 TI - Testing for changes in the SES-mortality gradient when the distribution of education changes too. AB - We develop a flexible test for changes in the SES-mortality gradient that accounts for changes in the distribution of education, the most commonly used marker of SES. We implement the test for the period between 1984 and 2006 in the United States using microdata from the Census and other surveys linked to death records. Using our flexible test, we find that the evidence for a change in the SES-mortality gradient is not as strong as previous research has suggested. Our results indicate that the gradient increased for females during this time period, but we cannot rule out that the gradient among males has not changed. Informally, the results suggest that the changes for females are mainly driven by the bottom of the education distribution. PMID- 26830226 TI - A Minor Subset of Super Elongation Complexes Plays a Predominant Role in Reversing HIV-1 Latency. AB - Promoter-proximal pausing by RNA polymerase II (Pol II) is a key rate-limiting step in HIV-1 transcription and latency reversal. The viral Tat protein recruits human super elongation complexes (SECs) to paused Pol II to overcome this restriction. Despite the recent progress in understanding the functions of different subsets of SECs in controlling cellular and Tat-activated HIV transcription, little is known about the SEC subtypes that help reverse viral latency in CD4(+) T cells. Here, we used the CRISPR-Cas9 genome-editing tool to knock out the gene encoding the SEC subunit ELL2, AFF1, or AFF4 in Jurkat/2D10 cells, a well-characterized HIV-1 latency model. Depletion of these proteins drastically reduced spontaneous and drug-induced latency reversal by suppressing HIV-1 transcriptional elongation. Surprisingly, a low-abundance subset of SECs containing ELL2 and AFF1 was found to play a predominant role in cooperating with Tat to reverse latency. By increasing the cellular level/activity of these Tat friendly SECs, we could potently activate latent HIV-1 without using any drugs. These results implicate the ELL2/AFF1-SECs as an important target in the future design of a combinatorial therapeutic approach to purge latent HIV-1. PMID- 26830227 TI - Aquaporin-3 Controls Breast Cancer Cell Migration by Regulating Hydrogen Peroxide Transport and Its Downstream Cell Signaling. AB - Most breast cancer mortality is due to clinical relapse associated with metastasis. CXCL12/CXCR4-dependent cell migration is a critical process in breast cancer progression; however, its underlying mechanism remains to be elucidated. Here, we show that the water/glycerol channel protein aquaporin-3 (AQP3) is required for CXCL12/CXCR4-dependent breast cancer cell migration through a mechanism involving its hydrogen peroxide (H2O2) transport function. Extracellular H2O2, produced by CXCL12-activated membrane NADPH oxidase 2 (Nox2), was transported into breast cancer cells via AQP3. Transient H2O2 accumulation was observed around the membrane during CXCL12-induced migration, which may be facilitated by the association of AQP3 with Nox2. Intracellular H2O2 then oxidized PTEN and protein tyrosine phosphatase 1B (PTP1B) followed by activation of the Akt pathway. This contributed to directional cell migration. The expression level of AQP3 in breast cancer cells was related to their migration ability both in vitro and in vivo through CXCL12/CXCR4- or H2O2-dependent pathways. Coincidentally, spontaneous metastasis of orthotopic xenografts to the lung was reduced upon AQP3 knockdown. These findings underscore the importance of AQP3-transported H2O2 in CXCL12/CXCR4-dependent signaling and migration in breast cancer cells and suggest that AQP3 has potential as a therapeutic target for breast cancer. PMID- 26830228 TI - SREBP-1c/MicroRNA 33b Genomic Loci Control Adipocyte Differentiation. AB - White adipose tissue (WAT) is essential for maintaining metabolic function, especially during obesity. The intronic microRNAs miR-33a and miR-33b, located within the genes encoding sterol regulatory element-binding protein 2 (SREBP-2) and SREBP-1, respectively, are transcribed in concert with their host genes and function alongside them to regulate cholesterol, fatty acid, and glucose metabolism. SREBP-1 is highly expressed in mature WAT and plays a critical role in promoting in vitro adipocyte differentiation. It is unknown whether miR-33b is induced during or involved in adipogenesis. This is in part due to loss of miR 33b in rodents, precluding in vivo assessment of the impact of miR-33b using standard mouse models. This work demonstrates that miR-33b is highly induced upon differentiation of human preadipocytes, along with SREBP-1. We further report that miR-33b is an important regulator of adipogenesis, as inhibition of miR-33b enhanced lipid droplet accumulation. Conversely, overexpression of miR-33b impaired preadipocyte proliferation and reduced lipid droplet formation and the induction of peroxisome proliferator-activated receptor gamma (PPARgamma) target genes during differentiation. These effects may be mediated by targeting of HMGA2, cyclin-dependent kinase 6 (CDK6), and other predicted miR-33b targets. Together, these findings demonstrate a novel role of miR-33b in the regulation of adipocyte differentiation, with important implications for the development of obesity and metabolic disease. PMID- 26830230 TI - De Novo RNA Synthesis by RNA-Dependent RNA Polymerase Activity of Telomerase Reverse Transcriptase. AB - RNA-dependent RNA polymerase (RdRP) plays key roles in RNA silencing to generate double-stranded RNAs. In model organisms, such as Caenorhabditis elegans and Neurospora crassa, two types of small interfering RNAs (siRNAs), primary siRNAs and secondary siRNAs, are expressed; RdRP produces secondary siRNAs de novo, without using either Dicer or primers, while primary siRNAs are processed by Dicer. We reported that human telomerase reverse transcriptase (TERT) has RdRP activity and produces endogenous siRNAs in a Dicer-dependent manner. However, de novo synthesis of siRNAs by human TERT has not been elucidated. Here we show that the TERT RdRP generates short RNAs that are complementary to template RNAs and have 5'-triphosphorylated ends, which indicates de novo synthesis of the RNAs. In addition, we confirmed short RNA synthesis by TERT in several human carcinoma cell lines and found that TERT protein levels are positively correlated with RdRP activity. PMID- 26830229 TI - Arrested Hematopoiesis and Vascular Relaxation Defects in Mice with a Mutation in Dhfr. AB - Dihydrofolate reductase (DHFR) is a critical enzyme in the folate metabolism pathway and also plays a role in regulating nitric oxide (NO) signaling in endothelial cells. Although both coding and noncoding mutations with phenotypic effects have been identified in the human DHFR gene, no mouse model is currently available to study the consequences of perturbing DHFR in vivo In order to identify genes involved in definitive hematopoiesis, we performed a forward genetic screen and produced a mouse line, here referred to as Orana, with a point mutation in the Dhfr locus leading to a Thr136Ala substitution in the DHFR protein. Homozygote Orana mice initiate definitive hematopoiesis, but expansion of progenitors in the fetal liver is compromised, and the animals die between embryonic day 13.5 (E13.5) and E14.5. Heterozygote Orana mice survive to adulthood but have tissue-specific alterations in folate abundance and distribution, perturbed stress erythropoiesis, and impaired endothelium-dependent relaxation of the aorta consistent with the role of DHFR in regulating NO signaling. Orana mice provide insight into the dual roles of DHFR and are a useful model for investigating the role of environmental and dietary factors in the context of vascular defects caused by altered NO signaling. PMID- 26830231 TI - A Novel Allosteric Mechanism of NF-kappaB Dimerization and DNA Binding Targeted by an Anti-Inflammatory Drug. AB - The NF-kappaB family plays key roles in immune and stress responses, and its deregulation contributes to several diseases. Therefore its modulation has become an important therapeutic target. Here, we used a high-throughput screen for small molecules that directly inhibit dimerization of the NF-kappaB protein p65. One of the identified inhibitors is withaferin A (WFA), a documented anticancer and anti inflammatory compound. Computational modeling suggests that WFA contacts the dimerization interface on one subunit and surface residues E285 and Q287 on the other. Despite their locations far from the dimerization site, E285 and Q287 substitutions diminished both dimerization and the WFA effect. Further investigation revealed that their effects on dimerization are associated with their proximity to a conserved hydrophobic core domain (HCD) that is crucial for dimerization and DNA binding. Our findings established NF-kappaB dimerization as a drug target and uncovered an allosteric domain as a target of WFA action. PMID- 26830232 TI - Lycopene, tomato products and prostate cancer-specific mortality among men diagnosed with nonmetastatic prostate cancer in the Cancer Prevention Study II Nutrition Cohort. AB - While dietary lycopene and tomato products have been inversely associated with prostate cancer incidence, there is limited evidence for an association between consumption of lycopene and tomato products and prostate-cancer specific mortality (PCSM). We examined the associations of prediagnosis and postdiagnosis dietary lycopene and tomato product intake with PCSM in a large prospective cohort. This analysis included men diagnosed with nonmetastatic prostate cancer between enrollment in the Cancer Prevention Study II Nutrition Cohort in 1992 or 1993 and June 2011. Prediagnosis dietary data, collected at baseline, were available for 8,898 men, of whom 526 died of prostate cancer through 2012. Postdiagnosis dietary data, collected on follow-up surveys in 1999 and/or 2003, were available for 5,643 men, of whom 363 died of prostate cancer through 2012. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for PCSM. Neither prediagnosis nor postdiagnosis dietary lycopene intake was associated with PCSM (fourth vs. first quartile HR = 1.00, 95% CI 0.78-1.28; HR = 1.22, 95% CI 0.91-1.64, respectively). Similarly, neither prediagnosis nor postdiagnosis consumption of tomato products was associated with PCSM. Among men with high-risk cancers (T3-T4 or Gleason score 8 10, or nodal involvement), consistently reporting lycopene intake >= median on both postdiagnosis surveys was associated with lower PCSM (HR = 0.41, 95% CI 0.17 0.99, based on ten PCSM cases consistently >= median intake) compared to consistently reporting intake < median. Future studies are needed to confirm the potential inverse association of consistently high lycopene intake with PCSM among men with high-risk prostate cancers. PMID- 26830233 TI - A longitudinal study of risk factors for shedding of VTEC O157 by young cattle in herds with known E. coli O157 carriage. AB - A longitudinal study in England and Wales of two dairy, five beef-fattener and three beef-suckler herds was carried out to identify risk factors for young cattle excreting verocytotoxin-producing Escherichia coli O157 (VTEC O157). A total of 1383 cattle, selected into cohorts at 0-24 months were sampled between March 2000 and February 2001. Mixed-effects logistic regression was employed to identify significant associations between VTEC O157 isolation from rectal faecal samples and explanatory factors (P < 0.001 unless shown). The results revealed a positive association with feeding root crops and a negative association with animals fed silage, milk (P = 0.001) or grain (P = 0.027). Cattle in suckler herds (P = 0.001) and those changing group between sampling visits were identified as negatively associated with VTEC O157 presence. The recovery of VTEC O157 varied throughout the year. However, the winter period from December to February was a risk factor in the multivariable analysis. Cattle in pens were 4.7 times more likely to shed VTEC O157 than those group-housed or at pasture. VTEC O157 detected in pooled environmental faecal pats and biofilm of the water supply within a group's enclosure were positively associated with an animal's VTEC O157 status in the multivariable logistic regression, as was detection of VTEC O157 in the pooled faecal pats at the previous visit. PMID- 26830237 TI - Spiritual Care Providers and Goals-of-Care Discussions. PMID- 26830238 TI - Proposed Guidelines for Future Vitamin D Studies. PMID- 26830239 TI - Spiritual Care Providers and Goals-of-Care Discussions--Reply. PMID- 26830240 TI - Proposed Guidelines for Future Vitamin D Studies. PMID- 26830241 TI - Proposed Guidelines for Future Vitamin D Studies. PMID- 26830242 TI - Proposed Guidelines for Future Vitamin D Studies--Reply. PMID- 26830243 TI - Finding the Balance of Less Is More. PMID- 26830244 TI - Finding the Balance of Less Is More. PMID- 26830245 TI - Biomarkers in the Diagnosis of ST-Segment Elevation Myocardial Infarction. PMID- 26830246 TI - Finding the Balance of Less is More--Reply. PMID- 26830247 TI - Incorrect Sentences in Discussion. PMID- 26830248 TI - Error in Wording in the Abstract and Methods Section and Reworded Figure 2 Title and Caption. PMID- 26830249 TI - Correction to Introduction and Figure. PMID- 26830250 TI - Errors in Sex Distribution. PMID- 26830251 TI - Factors impacting on patient perception of procedural success and satisfaction following treatment for varicose veins. AB - BACKGROUND: Patient-reported outcome measures (PROMs) have been collected from patients undergoing varicose vein treatments in the National Health Service since 2009. The aim of this retrospective cohort study was to examine PROMs for varicose vein interventions, characterizing factors that might predict patient reported perception of procedural success and satisfaction. METHODS: Centrally compiled PROMs data for varicose vein procedures carried out from 2009 to 2011 were obtained from the Hospital Episode Statistics data warehouse for England. As data were not distributed normally, non-parametric statistical tests were employed. RESULTS: Data for 35 039 patient episodes (62.8 per cent women) were available for analysis. Some 23.4 per cent of patients reported a degree of anxiety or depression before treatment; a formal diagnosis of depression was present in 7.8 per cent. Quality of life, measured by generic EQ-5D-3LTM index and the Aberdeen Varicose Vein Questionnaire (AVVQ) improved after intervention by 11.7 per cent (0.77 to 0.86) and 40.1 per cent (18.95 to 11.36) respectively. No significant improvement was found in EQ-5DTM visual analogue scale scores. There was a significant improvement in self-perceived anxiety or depression after the intervention (P < 0.001, McNemar-Bowker test). Both preoperative and postoperative depression or anxiety had a statistically significant relationship with self-reported success and satisfaction (both P < 0.001, chi(2) test). CONCLUSION: This analysis of PROMs is evidence that treatment of varicose veins improves quality of life, and anxiety or depression. Preoperative and postoperative anxiety or depression scores impact on patient-perceived success and satisfaction rates. PMID- 26830252 TI - Assessing productive efficiency and operating scale of community blood centers. AB - BACKGROUND: In recent years demand for blood products has decreased, and as a result, the blood product marketplace has become much more competitive. Reducing inefficiency in the procurement and processing of blood products at blood centers can reduce costs while assuring that demand for blood products is met. STUDY DESIGN AND METHODS: This study uses data envelopment analysis to compare the productive efficiency of 65 community blood centers to determine to what extent efficiency can be improved, what cost savings and increases in platelet (PLT) production may be obtained by eliminating inefficiency, and what scales of operation are the most efficient from a budgetary and staffing standpoint. Data were collected from the 2012 to 2013 AABB Directory of Community Blood Centers and Hospital Blood Banks. RESULTS: The study found that 27 of 65 blood centers are efficient. The remaining 38 blood centers can reduce budget and staff levels and may be able to expand output. If inefficient centers were to eliminate all inefficiency, the total savings would be $671 million, approximately 20% of the aggregated budget ($3.45 billion) of all centers in the study. In addition, the centers would also see a 36% increase in PLT production. Inefficiency of some large blood centers stems from operating at too large a scale, while inefficiency of most small blood centers is scale independent. CONCLUSION: The results suggest that reducing inefficiency in blood procurement may be a good strategy to maximize competitiveness in the blood product marketplace. These findings further suggest that the trend of blood center consolidation may be ill advised from a cost containment perspective. PMID- 26830253 TI - Galectin-3 and Soluble ST2 and Kidney Function Decline in Older Adults: The Cardiovascular Health Study (CHS). PMID- 26830254 TI - Thiazide Responsiveness Testing in Patients With Renal Magnesium Wasting and Correlation With Genetic Analysis: A Diagnostic Test Study. PMID- 26830255 TI - Estimated GFR Decline Following Sodium Phosphate Enemas Versus Polyethylene Glycol for Screening Colonoscopy: A Retrospective Cohort Study. AB - BACKGROUND: Associations between sodium phosphate enemas and nephropathy have raised concerns about the safety of use as part of a bowel-cleansing regimen administered prior to colonoscopies. The objectives of this analysis are to evaluate the impact of sodium phosphate enema versus polyethylene glycol powder for oral solution (PEG) use prior to colonoscopy screening on estimated glomerular filtration rate (eGFR) decline in Veterans Affairs (VA) patients and identify other risk factors contributing to eGFR decline. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 70,499 VA patients receiving sodium phosphate enemas (with or without PEG) or PEG alone prior to colonoscopy screenings. PREDICTOR: Use of either sodium phosphate or PEG. OUTCOMES: A 50% increase in serum creatinine level over a 15-month, over a 6-week, and between a 9- and 15-month period was used to define any, acute, or long-term eGFR decline, respectively. MEASUREMENTS: Multivariable logistic regressions estimated the likelihood of eGFR decline conditional on the use of sodium phosphate enemas versus PEG alone, controlling for potential confounders. RESULTS: A greater proportion of patients using sodium phosphate enemas versus PEG had any (P<0.001) or long-term (P=0.003) eGFR declines, whereas similar proportions had acute eGFR declines (P=0.9). In the adjusted analyses, use of sodium phosphate enemas (+/- PEG was associated with an increased likelihood of having any (OR, 1.3; 95% CI, 1.2-1.5) or long-term (OR, 1.4; 95% CI, 1.1-1.8) eGFR decline, but not acute eGFR decline (OR, 1.0; 95% CI, 0.6-1.7). Other risk factors for eGFR decline included diabetes and non-iron deficient anemia. LIMITATIONS: Unobserved heterogeneity due to volume depletion and potential selection bias due to higher-risk patients preferentially prescribed sodium phosphate enemas. CONCLUSIONS: Use of sodium phosphate enemas versus PEG alone prior to colonoscopy screening increases the risk for VA patients having long-term eGFR decline. Patients with non-iron deficient anemia are at particularly high risk for eGFR decline. These findings motivate the need to re-examine prescribing practices for sodium phosphate enemas as part of a bowel-cleansing regimen. PMID- 26830256 TI - Acute Kidney Injury in Low-Resource Settings: Barriers to Diagnosis, Awareness, and Treatment and Strategies to Overcome These Barriers. AB - Acute kidney injury (AKI) is increasingly recognized as a major health problem worldwide, responsible for an estimated 1.4 million deaths per year. The occurrence of and approach to AKI in low-resource settings (LRS) present special challenges due to often limited health care resources, including insufficient numbers of trained personnel, diagnostic tools, and treatment options. Although the International Society of Nephrology set a goal of eliminating preventable deaths from AKI by 2025, implementation of this program in LRS presents major challenges not only because of the lack of resources, but also because of the lack of awareness of the impact of AKI on patient outcomes, factors that are complicated by the challenge of cognitively dissociating the care of patients with AKI from the care of patients with chronic kidney failure. To better understand how to increase the awareness of AKI and develop strategies to improve the identification and treatment of patients with AKI in LRS, we administered an 18-item web-based questionnaire to physicians actively engaged in providing nephrology care in LRS. A checklist was then developed of meaningful and targeted approaches for implementation, with focus on engaging local and regional stakeholders, developing education programs and appropriate guidelines, enhancing training of health care workers, expanding health care resources, linking with other regional health care projects, and broadening research opportunities. PMID- 26830257 TI - Water-soluble, luminescent ZnTe quantum dots: supersaturation-controlled synthesis and self-assembly into nanoballs, nanonecklaces and nanowires. AB - A supersaturation-controlled aqueous synthesis route has been developed for ZnTe quantum dots (QDs) with high monodispersity, size tunability, stability, band edge luminescence (full-width at half-maximum (FWHM) 10-12 nm) and negligibly small Stokes' shift (2-4 nm). The degree of supersaturation of the initial reaction mixture was varied by increasing the reagent concentration, but keeping the molar ratio Zn(2+) : thioglycolic acid : Te(2-) constant at 1 : 2.5 : 0.5. For a 10* increase in supersaturation, the photoluminescence (PL) peak underwent a 50 nm blue shift from 330 to 280 nm at pH 6. The effect was more pronounced at pH 12, where the PL peak blue-shifted by 100 nm from 327 to 227 nm. Concomitantly, the FWHM was also reduced to a low value of 10 nm, indicating high monodispersity. For a 10* change in supersaturation, the particle size decreased by 63% (from 2.2 to 0.8 nm) at pH 12, whereas it changed by 19% (from 2.1 to 1.7 nm) at pH 6. High-resolution transmission electron microscopy and selected area electron diffraction data further revealed that the QDs synthesized at higher supersaturation had a better crystallinity. These QDs exhibited the unique property of undergoing isotropic and anisotropic self-assembly, which resulted in a blue shift and a red shift in the absorption and PL spectra, respectively. Isotropic assembly into spherical nanoballs (100 nm diameter, 1 nm inter-QD separation) occurred when the QDs were stored at pH 12 for 3 weeks at room temperature. The nanoballs further self-assembled into a 'pearl necklace' arrangement. On the partial removal of the capping agents, the QDs self-organized anisotropically into nanowires (1.3 MUm long and 4.6 nm in diameter). The self assembled nanostructures showed exciton-exciton coupling and excellent PL properties, which may be useful in enhanced optoelectronics, photovoltaics and biochemical sensing. PMID- 26830258 TI - Autism and Cancer Share Risk Genes, Pathways, and Drug Targets. AB - Autism is a neurodevelopmental disorder, diagnosed behaviorally by social and communication deficits, repetitive behaviors, and restricted interests. Recent genome-wide exome sequencing has revealed extensive overlap in risk genes for autism and for cancer. Understanding the genetic commonalities of autism(s) and cancer(s), with a focus on mechanistic pathways, could lead to repurposed therapeutics. PMID- 26830259 TI - Effect of Early Intervention With Positive Airway Pressure Therapy for Sleep Disordered Breathing on Six-Month Readmission Rates in Hospitalized Patients With Heart Failure. AB - Rehospitalization for congestive heart failure (CHF) is high within 6 months of discharge. Sleep disordered breathing (SDB) is common and underdiagnosed condition in patients with CHF. We hypothesized that early recognition and treatment of SDB in hospitalized patients with CHF will reduce hospital readmissions and emergency room visits. Patients admitted for CHF underwent overnight polysomnography within 4 weeks of discharge. Patients diagnosed with SDB were provided therapy with positive airway pressure therapy. Patients were identified as having good compliance if the device use was for a minimum of 4 hours 70% of the time for a minimum of 4 weeks during the first 3 months of therapy. Hospital admissions for 6 months before therapy were compared with readmission within 6 months after therapy in patients with good and poor compliance. A total of 70 patients were diagnosed with SDB after discharge. Of the 70 patients, 37 (53%) were compliant with positive airway pressure therapy. Compliant patients were more likely to be older (64 +/- 12 vs 58 +/- 11 years) and women (54% vs 33%) and less likely to be patient with diabetes (40% vs 67%) versus noncompliant patients. Although both groups experienced a decrease in total readmissions, compliant patients had a significant reduction (mean +/- SE: 1.5 +/- 0.2 clinical events vs -0.2 +/- 0.3; p <0.0001). In this single-center analysis, identification and treatment of SDB in admitted patients with CHF with SDB is associated with reduced readmissions over 6 months after discharge. Adherence to the treatment was associated with a greater reduction in clinical events. PMID- 26830261 TI - Role of Perfusion at Rest in the Diagnosis of Myocardial Infarction Using Vasodilator Stress Cardiovascular Magnetic Resonance. AB - In clinical practice, perfusion at rest in vasodilator stress single-photon emission computed tomography is commonly used to confirm myocardial infarction (MI) and ischemia and to rule out artifacts. It is unclear whether perfusion at rest carries similar information in cardiovascular magnetic resonance (CMR). We sought to determine whether chronic MI is associated with abnormal perfusion at rest on CMR. We compared areas of infarct and remote myocardium in 31 patients who underwent vasodilator stress CMR (1.5 T), had MI confirmed by late gadolinium enhancement (LGE scar), and coronary angiography within 6 months. Stress perfusion imaging during gadolinium first pass was followed by reversal with aminophylline (75 to 125 mg), rest perfusion, and LGE imaging. Resting and peak stress time-intensity curves were used to obtain maximal upslopes (normalized by blood pool upslopes), which were compared between infarcted and remote myocardial regions of interest. At rest, there was no significant difference between the slopes in the regions of interest supplied by arteries with and without stenosis >70% (0.31 +/- 0.16 vs 0.26 +/- 0.15 1/s), irrespective of LGE scar. However, at peak stress, we found significant differences (0.20 +/- 0.11 vs 0.30 +/- 0.22 1/s; p <0.05), reflecting the expected stress-induced ischemia. Similarly, at rest, there was no difference between infarcted and remote myocardium (0.27 +/- 0.14 vs 0.30 +/- 0.17 1/s), irrespective of stenosis, but significant differences were seen during stress (0.21 +/- 0.16 vs 0.28 +/- 0.18 1/s; p <0.001), reflecting inducible ischemia. In conclusion, abnormalities in myocardial perfusion at rest associated with chronic MI are not reliably detectable on CMR images. Accordingly, unlike single-photon emission computed tomography, normal CMR perfusion at rest should not be used to rule out chronic MI. PMID- 26830260 TI - Comparison of Insulin Resistance to Coronary Atherosclerosis in Human Immunodeficiency Virus Infected and Uninfected Men (from the Multicenter AIDS Cohort Study). AB - The relation between insulin resistance (IR) and coronary artery disease in patients with human immunodeficiency virus (HIV) infection remains incompletely defined. Fasting serum insulin and glucose measurements from 448 HIV-infected and 306 uninfected men enrolled in the Multicenter AIDS Cohort Study were collected at semiannual visits from 2003 to 2013 and used to compute the homeostatic model assessment of IR (HOMA-IR). Coronary computed tomographic angiography (CTA) was performed at the end of the study period to characterize coronary pathology. Associations between HOMA-IR (categorized into tertiles and assessed near the time of the CTA and over the 10-year study period) and the prevalence of coronary plaque or stenosis >=50% were assessed with multivariate logistic regression. HOMA-IR was higher in HIV-infected men than HIV-uninfected men when measured near the time of CTA (3.2 vs 2.7, p = 0.002) and when averaged over the study period (3.4 vs 3.0, p <0.001). The prevalence of coronary stenosis >=50% was similar between both groups (17% vs 15%, p = 0.41). Both measurements of HOMA-IR were associated with greater odds of coronary stenosis >=50% in models comparing men with values in the highest versus the lowest tertiles, although the effect of mean HOMA-IR was stronger than the single measurement of HOMA-IR before CTA (odds ratio 2.46, 95% CI 1.95 to 3.11, vs odds ratio 1.43, 1.20 to 1.70). This effect was not significantly modified by HIV serostatus. In conclusion, IR over nearly a decade was greater in HIV-infected men than HIV-uninfected men, and in both groups, was associated with significant coronary artery stenosis. PMID- 26830262 TI - Introduction. PMID- 26830264 TI - Educational Preparation of Nurses Caring for Older People with Cancer: An International Perspective. AB - OBJECTIVES: To review the education available in Europe and the US for nurses caring for older people with cancer. DATA SOURCES: Nursing literature, published guidelines, and professional nursing organizations Websites. CONCLUSION: The educational needs of nurses caring for older cancer patients have not been well defined to date, resulting in a mixed international picture of preparation. IMPLICATION FOR NURSING PRACTICE: As the number of older people with cancer grows, the resulting complexities of patient and family care needs have significant implications for the role of nursing. PMID- 26830265 TI - Models of Care in Geriatric Oncology Nursing. AB - OBJECTIVES: To review models of care for older adults with cancer, with a focus on the role of the oncology nurse in geriatric oncology care. International exemplars of geriatric oncology nursing care are discussed. DATA SOURCE: Published peer reviewed literature, Web-based resources, professional society materials, and the authors' experience. CONCLUSION: Nursing care for older patients with cancer is complex and requires integrating knowledge from multiple disciplines that blend the sciences of geriatrics, oncology, and nursing, and which recognizes the dimensions of quality of life. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses can benefit from learning key skills of comprehensive geriatric screening and assessment to improve the care they provide for older adults with cancer. PMID- 26830263 TI - The Evolution of Gero-Oncology Nursing. AB - OBJECTIVES: This article summarizes the evolution of gero-oncology nursing and highlights key educational initiatives, clinical practice issues, and research areas to enhance care of older adults with cancer. DATA SOURCES: Peer-reviewed literature, position statements, clinical practice guidelines, Web-based materials, and professional organizations' resources. CONCLUSION: Globally, the older adult cancer population is rapidly growing. The care of older adults with cancer requires an understanding of their diverse needs and the intersection of cancer and aging. Despite efforts to enhance competence in gero-oncology and to develop a body of evidence, nurses and health care systems remain under-prepared to provide high-quality care for older adults with cancer. IMPLICATIONS FOR NURSING PRACTICE: Nurses must take a leadership role in integrating gerontological principles into oncology settings. Working closely with interdisciplinary team members, nurses should utilize available resources and continue to build evidence through gero-oncology nursing research. PMID- 26830266 TI - The Role of the Advanced Practice Nurse in Geriatric Oncology Care. AB - OBJECTIVES: To describe how the Advanced Practice Nurse (APN) is uniquely suited to meet the needs of older adults throughout the continuum of cancer, to explore the progress that APNs have made in gero-oncology care, and make suggestions for future directions. DATA SOURCE: Google Scholar, PubMed, and CINAHL. Search terms included: "gero-oncology," "geriatric oncology," "Advanced Practice Nurse," "Nurse Practitioner," "older adult," "elderly," and "cancer." CONCLUSION: Over the last decade, APNs have made advances in caring for older adults with cancer by playing a role in prevention, screening, and diagnosis; through evidence-based gero-oncology care during cancer treatment; and in designing tailored survivorship care models. APNs must combat ageism in treatment choice for older adults, standardize comprehensive geriatric assessments, and focus on providing person-centered care, specifically during care transitions. IMPLICATIONS FOR NURSING PRACTICE: APNs are well-positioned to help understand the complex relationship between risk factors, geriatric syndromes, and frailty and translate research into practice. Palliative care must expand beyond specialty providers and shift toward APNs with a focus on early advanced care planning. Finally, APNs should continue to establish multidisciplinary survivorship models across care settings, with a focus on primary care. PMID- 26830267 TI - Geriatric Oncology Program Development and Gero-Oncology Nursing. AB - OBJECTIVES: To provide a critical analysis of current approaches to the care of older adults with cancer, outline priority areas for geriatric oncology program development, and recommend strategies for improvement. DATA SOURCES: Published articles and reports between 1999 and 2015. CONCLUSION: Providing an interdisciplinary model that incorporates a holistic geriatric assessment will ensure the delivery of patient-centered care that is responsive to the comprehensive needs of older patients. IMPLICATIONS FOR NURSING PRACTICE: Nursing administrators and leaders have both an opportunity and responsibility to shape the future of geriatric oncology. Preparations include workforce development and the creation of programs that are designed to meet the complex needs of this population. PMID- 26830268 TI - A Research Agenda for Gero-Oncology Nursing. AB - OBJECTIVES: The global challenge of accessible, affordable cancer care for all older adults requires a new research agenda for gero-oncology nursing to guide investigator skill development, identify priority areas for investigation, and direct resource distribution. DATA SOURCES: Published peer-reviewed literature and web-based resources. CONCLUSION: A cross-cutting theme of the research agenda is the need to determine the gero-oncology nursing care that will preserve economic resources, promote function, provide symptom management, and incorporate patient preferences. IMPLICATIONS FOR NURSING PRACTICE: In partnership with interprofessional colleagues, gero-oncology nurse scientists are poised to conduct global research that improves access to quality cancer care. PMID- 26830269 TI - The Future of Gero-Oncology Nursing. AB - OBJECTIVES: To project the future of gero-oncology nursing as a distinct specialty, framed between analysis of current challenges and explication of prospective solutions. DATA SOURCES: Peer-reviewed literature, policy directives, web-based resources, and author expertise. CONCLUSION: Oncology nursing faces several challenges in meeting the needs of older people living with cancer. Realigning cancer nursing education, practice, and research to match demographic and epidemiological realities mandates redesign. Viewing geriatric oncology as an optional sub-specialty limits oncology nursing, where older people represent the majority of oncology patients and cancer survivors. The future of gero-oncology nursing lies in transforming oncology nursing itself. IMPLICATIONS FOR NURSING PRACTICE: Specific goals to achieve transformation of oncology nursing into gero oncology nursing include assuring integrated foundational aging and cancer content across entry-level nursing curricula; assuring a gero-competent oncology nursing workforce with integrated continuing education; developing gero-oncology nurse specialists in advanced practice roles; and cultivating nurse leadership in geriatric oncology program development and administration along with expanding the scope and sophistication of gero-oncology nursing science. PMID- 26830270 TI - Sensorized pacifier to evaluate non-nutritive sucking in newborns. AB - We developed a device for an objective measurement of non-nutritive sucking (NNS). NNS is newborns' spontaneous action that is a predictor of their neural system development and can be adopted as an intervention to train oral feeding skills in preterms. Two miniaturized digital pressure sensors were embedded into a commercial pacifier and the two signals were simultaneously acquired using the Inter-Integrated circuit (I2C) interface. This solution traced a complete pressures profile of the sucking pattern in order to better understand the functional aspects of the two NNS phases, the suction and the expression. Experimental tests with nine newborns confirmed that the sensorized pacifier is an adequate tool for measuring NNS burst-pause patterns. The identified parameters related to the suction/expression rhythmicity could be used as indicators of the NNS ability. This device might be used both for exploring the possible diagnostic data contained in NNS pattern and for monitoring the sucking skills of premature infants. PMID- 26830271 TI - Evaluation of molecular and culture methods to determine the optimum testing strategy for verotoxigenic Escherichia coli in faecal specimens. AB - We evaluated 5 methods for the detection of verotoxogenic Escherichia coli (VTEC) from faecal specimens to determine the most sensitive and specific method(s) and to advise an optimum testing strategy. A total of 681 stool specimens were examined using up to 5 diagnostic molecular and phenotypic methods that are used routinely in the VTEC Reference laboratory, Dublin. A testing strategy incorporating a 2-step approach that included a single Real Time-PCR and 1 culture-based method yielded the highest sensitivity, specificity, positive predictive value, and negative predictive value of 98.21%, 100%, 100%, and 99.43%, respectively. PMID- 26830272 TI - A comparison of molecular assays for Mycoplasma pneumoniae in pediatric patients. AB - Three commercial molecular assays for detecting Mycoplasma pneumoniae were evaluated for their relative performances and hands-on time. They performed comparably well in clinical sensitivity and specificity. PMID- 26830273 TI - Shell-vial culture, coupled with real-time PCR, applied to Rickettsia conorii and Rickettsia massiliae-Bar29 detection, improving the diagnosis of the Mediterranean spotted fever. AB - Rickettsia conorii and Rickettsia massiliae-Bar29 are related to Mediterranean spotted fever (MSF). They are intracellular microorganisms. The Shell-vial culture assay (SV) improved Rickettsia culture but it still has some limitations: blood usually contains low amount of microorganisms and the samples that contain the highest amount of them are non-sterile. The objectives of this study were to optimize SV culture conditions and monitoring methods and to establish antibiotic concentrations useful for non-sterile samples. 12 SVs were inoculated with each microorganism, incubated at different temperatures and monitored by classical methods and real-time PCR. R. conorii was detected by all methods at all temperatures since 7th day of incubation. R. massiliae-Bar29 was firstly observed at 28 degrees C. Real-time PCR allowed to detected it 2-7 days earlier (depend on temperature) than classical methods. Antibiotics concentration needed for the isolation of these Rickettsia species from non-sterile samples was determined inoculating SV with R. conorii, R. massiliae-Bar29, biopsy or tick, incubating them with different dilutions of antibiotics and monitoring them weekly. To sum up, if a MSF diagnosis is suspected, SV should be incubated at both 28 degrees C and 32 degrees C for 1-3 weeks and monitored by a sensitive real-time PCR. If the sample is non-sterile the panel of antibiotics tested can be added. PMID- 26830274 TI - De novo assembly and annotation of the salivary gland transcriptome of Rhipicephalus appendiculatus male and female ticks during blood feeding. AB - Tick secretory proteins modulate haemostasis, inflammation and immune responses of the host and are attractive recombinant anti-tick vaccine candidates. Yet, many of the proteins have not been characterised due to the limited sequence availability for ticks and other arthropods for homology-based annotation. To address this limitation, we sequenced the salivary glands of the economically important adult male and female Rhipicephalus appendiculatus ticks during feeding. The quality-filtered Illumina sequencing reads were de novo assembled to generate a R. appendiculatus sialotranscriptome of 21,410 transcripts. A non redundant set of 12,761 R. appendiculatus proteins was predicted from the transcripts, including 2134 putative secretory and 8237 putative housekeeping proteins. Secretory proteins accounted for most of the expression in the salivary gland transcriptome (63%). Of the secretory protein class, the Glycine-rich superfamily contributed 66% and the Lipocalin family 12% of the transcriptome expression. Differential expression analysis identified 1758 female and 2346 male up-regulated transcripts, suggesting varying blood-feeding mechanisms employed between female and male ticks. The sialotranscriptome assembled in this work, greatly improves on the sequence information available for R. appendiculatus and is a valuable resource for potential future vaccine candidate selection. PMID- 26830275 TI - Ultrasound characteristics of thyroid nodules diagnosed as follicular neoplasms by fine-needle aspiration cytology. A prospective study with histological correlation. AB - Cytopathological evaluation has been proven useful in the diagnostic work-up of "cold" nodules. The cytological diagnosis of follicular neoplasm usually requires histology to exclude malignancy. The objective of this prospective study was to test the hypothesis that ultrasound examinations show distinct characteristics in a subgroup of nodules which may attest the benign nature of a follicular neoplasm. PATIENTS, METHODS: 56 patients (45 women, 11 men) were included in the study. All patients had a "cold" nodule which was diagnosed as follicular neoplasm. Consecutive histology revealed follicular adenomas (FTAs) (n = 44), follicular carcinomas (FTCs) (n = 7) and papillary carcinomas (PTCs) (n = 5), including follicular variant papillary carcinomas (fv PTCs) (n = 4). Ultrasound examinations were performed preoperatively. The ultrasound examinations were evaluated with respect to seven characteristics. RESULTS: In 21 % of patients a follicular neoplasm was associated with a malignant and in 79 % of patients with a benign tumor as compared with histology. The ultrasound characteristics size <= 2 ml, round shape and homogeneous structure revealed significant differences for FTAs, FTCs and PTCs with p < 0.001, p = 0.003 and p = 0.027, resp. With respect to the benign nature of a follicular neoplasm maximum values for sensitivity and specificity were 0.75 and 0.83. Multivariate discriminant analysis revealed that ultrasound criteria were suitable to discriminate between benign vs. malignant nodules and among FTAs, FTCs and PTCs with correlation coefficients of r = 0.53 and r = 0.74, resp. CONCLUSIONS: in selected patients with higher operative risks and cytological diagnosis of follicular neoplasm ultrasound parameters may be helpful to assume a benign nature of the neoplasm and thus avoid the necessity of a histological work-up. PMID- 26830276 TI - Prevalence of Hyperparathyroidism, Mineral and Bone Disorders in Children with Advanced Chronic Kidney Disease. AB - OBJECTIVE: To identify the prevalence and risk factors for secondary hyperparathyroidism in children with advanced stages of chronic kidney disease (CKD). METHODS: A retrospective cross-sectional observational study of clinical and laboratory data of pediatric patients with CKD stage 3, 4 was conducted from 2005 through 2013 at a single center in the Kingdom of Saudi Arabia. RESULTS: One hundred nineteen children (60.5 % boys) with mean age of 10.1 +/- 5.1 y were included in the study. The mean eGFR (estimated Glomerular Filtration Rate) was 18.3 +/- 15.4 ml/min/1.73m(2) and the mean intact parathyroid hormone (iPTH) level was 62.2 +/- 89.4 pmol/L. Patients with a high iPTH had lower eGFR than those who were euparathyroid (16 +/- 13.4 vs. 29.7 +/- 19 ml/min/1.73m(2), respectively; p = 0.006), had lower calcium levels (2.2 +/- 0.3 vs. 2.4 +/- 0.3 mmol/L; p = 0.03) and a lower bicarbonate level (21.2 +/- 4.2 vs. 23.3 +/- 3.2 mmol/L; p = 0.04). Three children with hyperparthyrodism (4.9 %) had fractures, 16 (26.2 %) had bone deformities compared to 5 in the euoparathyroid group (p = 0.012). Parathyroid hormone negatively correlated with the patient's eGFR (r = 0.55), serum calcium (r = -0.43), and positively correlated with serum phosphate (r = 0.38). CONCLUSIONS: The single most important predictor of hyperparathyroidism in children in the present sample was eGFR. PMID- 26830277 TI - A Child with Recurrent Abdominal Pain: A Cross-road between Pediatrics, Neurology and Psychiatry. PMID- 26830278 TI - Cartilage Hair Hypoplasia: Two Unrelated Cases with g.70 A > G Mutation in RMRP Gene. AB - Cartilage-hair hypoplasia is an autosomal recessive disorder, characterized by short stature, metaphyseal dysplasia, hypotrichosis and immunodeficiency. More than 90 different biallelic mutations in RMRP gene have been identified to cause this condition. Three cases previously reported from India showed novel mutations in RMRP gene. The authors report two unrelated cases with the more common g.70A > G mutation, stressing the need to screen for this mutation in Indian population having features of cartilage-hair hypoplasia. PMID- 26830279 TI - Intravenous Colistimethate Sodium in Neonatal Sepsis. PMID- 26830280 TI - Ultrasound Examination of Pediatric Musculoskeletal Diseases and Neonatal Spine. AB - Ultrasound (US) is a simple, non-invasive imaging modality which allows high resolution imaging of the musculoskeletal (MSK) system. Its increasing popularity in pediatrics is due to the fact that it does not involve radiation, has an ability to visualize non-ossified cartilaginous and vascular structures, allows dynamic imaging and quick contralateral comparison. US is the primary imaging modality in some pediatric MSK conditions like infant hip in developmental dysplasia (DDH), hip joint effusion, epiphyseal trauma and evaluation of the neonatal spine. US is the modality of choice in infants with DDH, both in the initial evaluation and post-treatment follow-up. US has a sensitivity equivalent to MRI in evaluation of the neonatal spine in experienced hands and is a good screening modality in neonates with suspected occult neural tube defects. In other MSK applications, it is often used for the initial diagnosis or in addition to other imaging modalities. In trauma and infections, US can often detect early and subtle soft tissue abnormalities and a quick comparison with the contralateral side aids in diagnoses. Dynamic imaging is crucial in evaluating congenital instabilities and dislocations, soft tissue and ligamentous injuries, epiphyseal injuries and fracture separations. High-resolution imaging along with color Doppler (CD) is useful in the characterization of soft tissue masses. This article reviews the applications of US in pediatric MSK with emphasis on conditions where it is a primary modality. Limitations of US include inability to penetrate bone, hence, limited diagnosis of intraosseous pathology and operator dependency. PMID- 26830281 TI - Celiac Disease Presenting with Biotinidase Deficiency and Paraplegia. PMID- 26830282 TI - Lysosomal Storage Disorders in Egyptian Children. AB - OBJECTIVE: To describe the spectrum, relative prevalence and molecular background of lysosomal storage disorders in Egypt. METHODS: The authors evaluated the selective screening program for the diagnosis of lysosomal storage disorders in Egyptian children presenting to the inherited metabolic disease unit at Cairo University Children's Hospital, the largest tertiary care pediatric hospital in Egypt, over a six-year period (April 2008 through April 2014). During this period, 1,065 suspected children were assessed clinically, biochemically and some genetically. RESULTS: Two hundred and eleven children (aged 44 +/- 32 mo; 56 % boys, 82 % with consanguineous parents) were confirmed with 21 different lysosomal disorders. The diagnostic gap ranged between 2 mo and 14 y (average 25 mo). Mucopolysaccharidoses were the most common group of diseases diagnosed (44.5 %), while Maroteaux-Lamy, Gaucher and nephropathic cystinosis were the most commonly detected syndromes (17.1, 14.7 and 13.7 %, respectively). Eighty mutant alleles and 17 pathogenic mutations were detected in 48 genetically assessed confirmed patients (30 Gaucher, 16 cystinosis and two Niemann-Pick type C patients). CONCLUSIONS: This report is the first to describe relative frequency and spectrum of clinical and molecular data in a large cohort of Egyptian lysosomal patients. The crude estimate denotes that over 80 % of Egyptian lysosomal patients do not have access to optimal diagnosis. Upgrading diagnostic and genetic services for lysosomal storage disorders in Egypt is absolutely necessary. PMID- 26830283 TI - Modeling and Cost-Effectiveness in HIV Prevention. AB - With HIV funding plateauing and the number of people living with HIV increasing due to the rollout of life-saving antiretroviral therapy, policy makers are faced with increasingly tighter budgets to manage the ongoing HIV epidemic. Cost effectiveness and modeling analyses can help determine which HIV interventions may be of best value. Incidence remains remarkably high in certain populations and countries, making prevention key to controlling the spread of HIV. This paper briefly reviews concepts in modeling and cost-effectiveness methodology and then examines results of recently published cost-effectiveness analyses on the following HIV prevention strategies: condoms and circumcision, behavioral- or community-based interventions, prevention of mother-to-child transmission, HIV testing, pre-exposure prophylaxis, and treatment as prevention. We find that the majority of published studies demonstrate cost-effectiveness; however, not all interventions are affordable. We urge continued research on combination strategies and methodologies that take into account willingness to pay and budgetary impact. PMID- 26830285 TI - Novel Imaging Methods for Analysis of Tissue Resident Cells in HIV/SIV. AB - The use of advanced tissue-imaging methodologies has greatly facilitated the study of molecular mechanisms and cellular interactions in humans and animal models of disease. Particularly, in HIV research, there is an ever-increasing demand for a comprehensive analysis of immune cell dynamics at tissue level stemming from the need to advance our understanding of those interactions that regulate the generation of adaptive antigen-specific immune responses. The latter is critical for the development of vaccines to elicit broadly neutralizing antibodies as well as for the discovery of novel targets for immuno-therapies to strengthen the cytolytic arm of the immune system at local level. In this review, we focus on current and emerging imaging technologies, discuss their strengths and limitations, and examine how such technologies can inform the development of new treatments and vaccination strategies. We also present some perspective on the future of the technology development. PMID- 26830286 TI - From complex questionnaire and interviewing data to intelligent Bayesian network models for medical decision support. AB - OBJECTIVES: (1) To develop a rigorous and repeatable method for building effective Bayesian network (BN) models for medical decision support from complex, unstructured and incomplete patient questionnaires and interviews that inevitably contain examples of repetitive, redundant and contradictory responses; (2) To exploit expert knowledge in the BN development since further data acquisition is usually not possible; (3) To ensure the BN model can be used for interventional analysis; (4) To demonstrate why using data alone to learn the model structure and parameters is often unsatisfactory even when extensive data is available. METHOD: The method is based on applying a range of recent BN developments targeted at helping experts build BNs given limited data. While most of the components of the method are based on established work, its novelty is that it provides a rigorous consolidated and generalised framework that addresses the whole life-cycle of BN model development. The method is based on two original and recent validated BN models in forensic psychiatry, known as DSVM-MSS and DSVM-P. RESULTS: When employed with the same datasets, the DSVM-MSS demonstrated competitive to superior predictive performance (AUC scores 0.708 and 0.797) against the state-of-the-art (AUC scores ranging from 0.527 to 0.705), and the DSVM-P demonstrated superior predictive performance (cross-validated AUC score of 0.78) against the state-of-the-art (AUC scores ranging from 0.665 to 0.717). More importantly, the resulting models go beyond improving predictive accuracy and into usefulness for risk management purposes through intervention, and enhanced decision support in terms of answering complex clinical questions that are based on unobserved evidence. CONCLUSIONS: This development process is applicable to any application domain which involves large-scale decision analysis based on such complex information, rather than based on data with hard facts, and in conjunction with the incorporation of expert knowledge for decision support via intervention. The novelty extends to challenging the decision scientists to reason about building models based on what information is really required for inference, rather than based on what data is available and hence, forces decision scientists to use available data in a much smarter way. PMID- 26830284 TI - Fat Matters: Understanding the Role of Adipose Tissue in Health in HIV Infection. AB - More than one-third of adults in the USA are obese and obesity-related disease accounts for some of the leading causes of preventable death. Mid-life obesity may be a strong predictor of physical function impairment later in life regardless of body mass index (BMI) in older age, highlighting the benefits of obesity prevention on health throughout the lifespan. Adipose tissue disturbances including lipodystrophy and obesity are prevalent in the setting of treated and untreated HIV infection. This article will review current knowledge on fat disturbances in HIV-infected persons, including therapeutic options and future directions. PMID- 26830287 TI - Topological characteristics of target genes regulated by abiotic-stress responsible miRNAs in a rice interactome network. AB - A great number of microRNAs (miRNAs) have been identified in responding and acting in gene regulatory networks associated with plant tolerance to abiotic stress conditions, such as drought, salinity, and high temperature. The topological exploration of target genes regulated by abiotic-stress-responsible miRNAs (ASRmiRs) in a network facilitates to discover the molecular basis of plant abiotic stress response. This study was based on the staple food rice (Oryza sativa) in which ASRmiRs were manually curated. After having compared the topological properties of target genes (stress-miR-targets) with those (non stress-miR-targets) not regulated by ASRmiRs in a rice interactome network, we found that stress-miR-targets exhibited distinguishable topological properties. The interaction probability analysis and k-core decomposition showed that stress miR-targets preferentially interacted with non-stress-miR-targets and located at the peripheral positions in the network. Our results indicated an obvious topological distinction between the two types of genes, reflecting the specific mechanisms of action of stress-miR-targets in rice abiotic stress response. Also, the results may provide valuable clues to elucidate molecular mechanisms of crop response to abiotic stress. PMID- 26830288 TI - 40 Year Anniversary Issue of Neurochemical Research. PMID- 26830289 TI - Inhibiting Matrix Metalloproteinase 3 Ameliorates Neuronal Loss in the Ganglion Cell Layer of Rats in Retinal Ischemia/Reperfusion. AB - It has been demonstrated that matrix metalloproteinase 3 (MMP3) is integrally involved in the neuronal degeneration of the central nervous system by promoting glial activation, neuronal apoptosis and damage to the brain-blood barrier. However, whether MMP3 also contributes to the neuronal degeneration induced by retinal ischemia/reperfusion is still uncertain. In the present study, we detected the cellular localization of MMP3 in adult rat retinae and explored the relationship of its expression with neuronal loss in the ganglion cell layer (GCL) in retinal ischemia/reperfusion. We found that MMP3 was widely expressed in many cells throughout the layers of the rat retinae, including Vertebrate neuron specific nuclear protein (NeuN)-, parvalbumin-, calbindin-, protein kinase C alpha-, glial fibrillary acidic protein-, glutamine synthetase- and CD11b positive cells. Furthermore, all rats were treated with high intraocular pressure (HIOP) for 1 h (h) and sacrificed at 6 h, 1 day (d), 3 d, and 7 d after HIOP. Compared to the normal control, the expression of both proenzyme MMP3 and active MMP3 were significantly up-regulated after HIOP treatment without alteration of the laminar distribution pattern. Moreover, inhibiting MMP3 ameliorated the loss of NeuN-positive cells in the GCL following HIOP. In summary, our data demonstrates that MMP3 is expressed in multiple types of neurons and glial cells in normal rat retinae. Simultaneously, the up-regulation of its expression and activity are closely involved in neuronal loss in the GCL in retinal ischemia/reperfusion. PMID- 26830290 TI - Effect of the Anti-depressant Sertraline, the Novel Anti-seizure Drug Vinpocetine and Several Conventional Antiepileptic Drugs on the Epileptiform EEG Activity Induced by 4-Aminopyridine. AB - Seizures are accompanied by an exacerbated activation of cerebral ion channels. 4 aminopyridine (4-AP) is a pro-convulsive agent which mechanism of action involves activation of Na(+) and Ca(2+) channels, and several antiepileptic drugs control seizures by reducing these channels permeability. The antidepressant, sertraline, and the anti-seizure drug vinpocetine are effective inhibitors of cerebral presynaptic Na(+) channels. Here the effectiveness of these compounds to prevent the epileptiform EEG activity induced by 4-AP was compared with the effectiveness of seven conventional antiepileptic drugs. For this purpose, EEG recordings before and at three intervals within the next 30 min following 4-AP (2.5 mg/kg, i.p.) were taken in anesthetized animals; and the EEG-highest peak amplitude values (HPAV) calculated. In control animals, the marked increase in the EEG-HPAV observed near 20 min following 4-AP reached its maximum at 30 min. Results show that this epileptiform EEG activity induced by 4-AP is prevented by sertraline and vinpocetine at a dose of 2.5 mg/kg, and by carbamazepine, phenytoin, lamotrigine and oxcarbazepine at a higher dose (25 mg/kg). In contrast, topiramate (25 mg/kg), valproate (100 mg/kg) and levetiracetam (100 mg/kg) failed to prevent the epileptiform EEG activity induced by 4-AP. It is concluded that 4 AP is a useful tool to elicit the mechanism of action of anti-seizure drugs at clinical meaningful doses. The particular efficacy of sertraline and vinpocetine to prevent seizures induced by 4-AP is explained by their high effectiveness to reduce brain presynaptic Na(+) and Ca(2+) channels permeability. PMID- 26830291 TI - Morphine Inhibited the Rat Neural Stem Cell Proliferation Rate by Increasing Neuro Steroid Genesis. AB - Up to present, a large number of reports unveiled exacerbating effects of both long- and short-term administration of morphine, as a potent analgesic agent, on opium-addicted individuals and a plethora of cell kinetics, although contradictory effect of morphine on different cells have been introduced until yet. To address the potent modulatory effect of morphine on neural multipotent precursors with emphasis on endogenous sex-related neurosteroids biosynthesis, we primed the rat neural stem cells isolated from embryonic rat telencephalon to various concentrations of morphine including 10, 20, 50 and 100 uM alone or in combination with naloxone (100 uM) over period of 72 h. Flow cytometric Ki-67 expression and Annexin-V/PI based necrosis and apoptosis of exposed cells were evaluated. The total content of dihydrotestosterone and estradiol in cell supernatant was measured by ELISA. According on obtained data, both concentration and time-dependent decrement of cell viability were orchestrated thorough down regulation of ki-67 and simultaneous up-regulation of Annexin-V. On the other hand, the addition of naloxone (100 uM), as Mu opiate receptor antagonist, could blunt the morphine-induced adverse effects. It also well established that time course exposure of rat neural stem cells with morphine potently could accelerate the endogenous dihydrotestosterone and estradiol biosynthesis. Interestingly, naloxone could consequently attenuate the enhanced neurosteroidogenesis time dependently. It seems that our results discover a biochemical linkage between an accelerated synthesis of sex-related steroids and rat neural stem cells viability. PMID- 26830292 TI - Relative contribution of soil, management and traits to co-variations of multiple ecosystem properties in grasslands. AB - Ecological intensification promotes the better use of ecosystem functioning for agricultural production and as a provider of additional regulation and cultural services. We investigated the mechanisms underpinning potential ecological intensification of livestock production in the Vercors mountains (France). We quantified the variations in seven ecosystem properties associated with key ecosystem services: above-ground biomass production at first harvest, fodder digestibility, plant species richness, soil organic matter content, soil carbon content, total microbial biomass and soil bacteria:fungi ratio across 39 grassland plots representing varying management types and intensity. Our analyses confirmed joint effects of management, traits and soil abiotic parameters on variations in ecosystem properties, with the combination of management and traits being most influential. The variations explained by traits were consistent with the leaf economics spectrum model and its implications for ecosystem functioning. The observed independence between ecosystem properties relevant to production (forage biomass, digestibility and nutrient turnover) on the one hand and soil stocks (organic matter, carbon and microbial stocks) on the other hand suggests that an intensification of fodder production might be compatible with the preservation of the soil capital. We highlight that appropriate choices regarding various practices, such as the first date of grazing or mowing being dependent on soil moisture, have important consequences on a number of ecosystem properties relevant for ecosystem services and may influence biodiversity patterns. Such avenues for ecological intensification should be considered as part of further landscape- and farm-scale analyses of the relationships between farm functioning and ecosystem services. PMID- 26830293 TI - An invasive slug exploits an ant-seed dispersal mutualism. AB - Plant-animal mutualisms, such as seed dispersal, are often vulnerable to disruption by invasive species. Here, we show for the first time how a non-ant invasive species negatively affects seed dispersal by ants. We examined the effects of several animal species that co-occur in a temperate deciduous forest including native and invasive seed-dispersing ants (Aphaenogaster rudis and Myrmica rubra, respectively), an invasive slug (Arion subfuscus), and native rodents-on a native myrmecochorous plant, Asarum canadense. We experimentally manipulated ant, slug, and rodent access to seed depots and measured seed removal. We also video-recorded depots to determine which other taxa interact with seeds. We found that A. rudis was the main disperser of seeds and that A. subfuscus consumed elaiosomes without dispersing seeds. Rodent visitation was rare, and rodent exclusion had no significant effect on seed or elaiosome removal. We then used data obtained from laboratory and field mesocosm experiments to determine how elaiosome robbing by A. subfuscus affects seed dispersal by A. rudis and M. rubra. We found that elaiosome robbing by slugs reduced seed dispersal by ants, especially in mesocosms with A. rudis, which picks up seeds more slowly than M. rubra. Taken together, our results show that elaiosome robbing by an invasive slug reduces seed dispersal by ants, suggesting that invasive slugs can have profound negative effects on seed dispersal mutualisms. PMID- 26830296 TI - [CD22 and CD72 are inhibitory receptors dominantly expressed in B lymphocytes and regulate systemic autoimmune diseases. German version]. PMID- 26830294 TI - Incremental and Predictive Validity of the Antisocial Process Screening Device in a Community Sample of Male and Female Ethnic Minority and Caucasian Youth. AB - The Antisocial Process Screening Device (APSD) is a well-supported tool for assessing psychopathic features in youth. However, most research with the APSD has been derived from clinical and forensic samples comprised mainly of male Caucasian and African American adolescents. In this prospective study, the incremental and predictive validity of the self-report APSD for violent and non violent offending was examined in an ethnically diverse community sample of male and female youth (N = 335) aged 12 to 14. High-school students from a moderate sized city in Western Canada completed the self-report APSD and then completed the Self-Report of Offending 6 months later. Receiver Operating Characteristics analysis indicated that APSD total and subscale scores were predictive of violent and non-violent offending at 6-month follow-up with moderate to large effect sizes. In addition, total scores on the APSD added incremental predictive utility above and beyond traditional criminogenic predictors of youth offending (i.e., prior offending, delinquent peer affiliation, poor school achievement, substance use, low parental monitoring). Although sex differences emerged in the predictive utility of the Impulsivity subscale of the APSD vis-a-vis violent offending, sex did not moderate the relationship between APSD total, Narcissism, or Callous/Unemotional scores and offending. In addition, the predictive utility of the APSD did not vary as a function of the youth's ethnic background. These findings suggest that: (1) the self-report APSD may have utility for risk or threat assessment with normative school populations, (2) APSD findings from higher risk samples generalize to a lower risk sample of high-school youth, and (3) predictive utility of APSD total scores do not differ across male and female Caucasian and ethnic minority youth. PMID- 26830297 TI - Violence and Victimization During Incarceration: Relations to Psychosocial Adjustment During Reentry to the Community. AB - We surveyed male ex-offenders (N = 100) about their experiences during and prior to incarceration to assess the role of these factors in psychosocial adjustment postrelease. Participants completed measures of preincarceration mental health problems and severe victimization and feelings of safety during incarceration; they also self-reported emotional distress, antisocial behavior, and posttraumatic stress (PTS). Moderator analyses of PTS outcomes revealed two key interactions between preincarceration mental health problems and severe victimization during incarceration as well as preincarceration mental health problems by feelings of safety during incarceration. In those without preincarceration mental health problems, victimization and PTS were significantly positively related; this was not the case for those with preexisting mental problems. Furthermore, the positive relation between feeling unsafe and PTS was stronger among those with preexisting mental problems. Findings are discussed with respect to implications for reentry services. PMID- 26830298 TI - [(123)]FP-CIT SPECT scans initially rated as normal became abnormal over time in patients with probable dementia with Lewy bodies. AB - PURPOSE: Decreased striatal dopamine transporter (DAT) binding on SPECT imaging is a strong biomarker for the diagnosis of dementia with Lewy bodies (DLB). There is still a lot of uncertainty about patients meeting the clinical criteria for probable DLB who have a normal DAT SPECT scan (DLB/S-). The aim of this study was to describe the clinical and imaging follow-up in these patients, and compare them to DLB patients with abnormal baseline scans (DLB/S+). METHODS: DLB patients who underwent DAT imaging ([(123)I]FP-CIT SPECT) were selected from the Amsterdam Dementia Cohort. All [(123)I]FP-CIT SPECT scans were evaluated independently by two nuclear medicine physicians and in patients with normal scans follow-up imaging was obtained. We matched DLB/S-- patients for age and disease duration to DLB/S+ patients and compared their clinical characteristics. RESULTS: Of 67 [(123)I]FP-CIT SPECT scans, 7 (10.4 %) were rated as normal. In five DLB/S- patients, a second [(123)I]FP-CIT SPECT was performed (after on average 1.5 years) and these scans were all abnormal. No significant differences in clinical characteristics were found at baseline. DLB/S- patients could be expected to have a better MMSE score after 1 year. CONCLUSION: This study was the first to investigate DLB patients with the initial [(123)I]FP-CIT SPECT scan rated as normal and subsequent scans during disease progression rated as abnormal. We hypothesize that DLB/S- scans could represent a relatively rare DLB subtype with possibly a different severity or spread of alpha-synuclein pathology ("neocortical predominant subtype"). In clinical practice, if an alternative diagnosis is not imminent in a DLB/S- patient, repeating [(123)I]FP-CIT SPECT should be considered. PMID- 26830300 TI - White Paper on studying the safety of the childhood immunization schedule in the Vaccine Safety Datalink. AB - While the large majority of parents in the U.S. vaccinate their children according to the recommended immunization schedule, some parents have refused or delayed vaccinating, often citing safety concerns. In response to public concern, the U.S. Institute of Medicine (IOM) evaluated existing research regarding the safety of the recommended immunization schedule. The IOM concluded that although available evidence strongly supported the safety of the currently recommended schedule as a whole, additional observational research was warranted to compare health outcomes between fully vaccinated children and those on a delayed or alternative schedule. In addition, the IOM identified the Vaccine Safety Datalink (VSD) as an important resource for conducting this research. Guided by the IOM findings, the Centers for Disease Control and Prevention (CDC) commissioned a White Paper to assess how the VSD could be used to study the safety of the childhood immunization schedule. Guided by subject matter expert engagement, the resulting White Paper outlines a 4 stage approach for identifying exposure groups of undervaccinated children, presents a list of health outcomes of highest priority to examine in this context, and describes various study designs and statistical methods that could be used to analyze the safety of the schedule. While it appears feasible to study the safety of the recommended immunization schedule in settings such as the VSD, these studies will be inherently complex, and as with all observational studies, will need to carefully address issues of confounding and bias. In light of these considerations, decisions about conducting studies of the safety of the schedule will also need to assess epidemiological evidence of potential adverse events that could be related to the schedule, the biological plausibility of an association between an adverse event and the schedule, and public concern about the safety of the schedule. PMID- 26830299 TI - FDG PET/CT texture analysis for predicting the outcome of lung cancer treated by stereotactic body radiation therapy. AB - INTRODUCTION: With (18)F-FDG PET/CT, tumor uptake intensity and heterogeneity have been associated with outcome in several cancers. This study aimed at investigating whether (18)F-FDG uptake intensity, volume or heterogeneity could predict the outcome in patients with non-small cell lung cancers (NSCLC) treated by stereotactic body radiation therapy (SBRT). METHODS: Sixty-three patients with NSCLC treated by SBRT underwent a (18)F-FDG PET/CT before treatment. Maximum and mean standard uptake value (SUVmax and SUVmean), metabolic tumoral volume (MTV), total lesion glycolysis (TLG), as well as 13 global, local and regional textural features were analysed. The predictive value of these parameters, along with clinical features, was assessed using univariate and multivariate analysis for overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). Cutoff values were obtained using logistic regression analysis, and survivals were compared using Kaplan-Meier analysis. RESULTS: The median follow up period was 27.1 months for the entire cohort and 32.1 months for the surviving patients. At the end of the study, 25 patients had local and/or distant recurrence including 12 who died because of the cancer progression. None of the clinical variables was predictive of the outcome, except age, which was associated with DFS (HR 1.1, P = 0.002). None of the (18)F-FDG PET/CT or clinical parameters, except gender, were associated with OS. The univariate analysis showed that only dissimilarity (D) was associated with DSS (HR = 0.822, P = 0.037), and that several metabolic measurements were associated with DFS. In multivariate analysis, only dissimilarity was significantly associated with DSS (HR = 0.822, P = 0.037) and with DFS (HR = 0.834, P < 0.01). CONCLUSION: The textural feature dissimilarity measured on the baseline (18)F-FDG PET/CT appears to be a strong independent predictor of the outcome in patients with NSCLC treated by SBRT. This may help selecting patients who may benefit from closer monitoring and therapeutic optimization. PMID- 26830301 TI - French Health Technology Assessment of Antineoplastic Drugs Indicated in the Treatment of Solid Tumours: Perspective for Future Trends. AB - BACKGROUND: France is one of the European countries that spend the most on oncology drugs. To keep pharmaceutical expenditure under control, Health Authorities highly scrutinize market access of costly medicines. OBJECTIVE: To assess current and future trends in French health technology assessment (HTA) of antineoplastic drugs indicated in the treatment of solid tumours. METHODS: A review of the SMR and ASMR drivers of the Transparency Committee (CT) opinions issued for antineoplastic drugs indicated in the treatment of solid tumours and approved between 2009 and 2014 was performed to assess current trends in French health technology assessment (HTA), complemented by an expert board consultation to capture the critical issues on the future of antineoplastic drugs HTA. RESULTS: Thirty-one drugs indicated for the treatment of solid tumours were identified (77 % targeted therapies). Initial CT assessments were available for 26 drugs. Four key items in the CT assessment were identified: 1) Clinical trial methodology; 2) Acceptance of progression-free survival (PFS) as a valuable endpoint; 3) Transferability of clinical trials in clinical practice; 4) Unpredictability of CT decisions. Experts raised the important development of personalised medicines in oncology and key challenges for oncology products to generate information expected from HTA perspective. CONCLUSION: The French system remains committed to its values and philosophy (access of all innovations for everybody) which are threatened by the increasing launch of innovative therapies and budget constraint. Both HTA decision framework evolution and revision of the current pricing process should be considered in France to cope with these new challenges. PMID- 26830302 TI - Use of Aloe vera-based extender for chilling and freezing collared peccary (Pecari tajacu) semen. AB - As an alternative for the conservation of collared peccary semen, this research aims at evaluating the use of Aloe vera (AV) extract as a cryoprotectant for semen chilling and freezing. Five ejaculates were divided in two aliquots that were diluted in Tris plus egg yolk (EY; 20%) or AV extract (20%) and chilled at 5 degrees C. In both treatments, an adequate semen conservation was achieved and values closer to 40% motile sperm with viability and osmotic response ranging from 20% to 40%, and normal morphology of 80% were found after 36 hours of storage. Moreover, 12 other ejaculates were diluted in Tris plus EY (20%) or AV extract (5, 10, or 20%) and glycerol (3%). Samples were frozen in liquid nitrogen and thawed after 1 week. After thawing, all the treatments containing EY or AV provided similar values for sperm morphology, viability, osmotic response, membrane integrity, sperm motility, amplitude of lateral head, beat cross frequency, and rapid, low, and static subpopulations, but the highest values for straightness and the lowest values for curvilinear velocity were found using 20% AV (P < 0.05). In conclusion, we found that AV extract at a 20% concentration could be used as an alternative substitute to EY in the formulation of Tris extenders for collared peccaries' semen chilling or freezing. PMID- 26830304 TI - European Academy of Paediatric Dentistry guideline production. PMID- 26830303 TI - [Diagnostics and treatment strategies for multiple trauma patients]. AB - Severe trauma is still one of the leading causes of death worldwide. The initial treatment and diagnostics are of immense importance in polytraumatized patients. The initial approach mainly focuses on the advanced trauma life support (ATLS) concept. This includes the identification of life-threatening conditions and application of life-saving interventions. Depending on the physiological condition of the patient, the surgical treatment strategies of early total care (ETC) or damage control orthopedics (DCO) can be chosen. Appropriate surgical management can reduce the incidence of associated delayed systemic complications. This review summarizes the most commonly used definitions of polytrauma (including the Berlin polytrauma definition) and classification systems of severely injured patients. Moreover, the recently introduced treatment strategy of the safe definitive surgery concept for severely injured patients is also discussed in this article. PMID- 26830305 TI - Gloves, gowns and masks for reducing the transmission of methicillin-resistant Staphylococcus aureus (MRSA) in the hospital setting (Review). PMID- 26830306 TI - Feasibility and efficacy of gentamicin for treating neonatal sepsis in community based settings: a systematic review. AB - BACKGROUND: Neonatal sepsis is a leading cause of neonatal deaths in developing countries. The current recommended in-hospital treatment is parenteral ampicillin (or penicillin) and gentamicin in young infants for 10- 14 days; however, very few could access and afford. The current review is to evaluate the feasibility of gentamicin in community based settings. METHODS: Both observational and randomized controlled trials were included. Medline, Embase, Cochrane Central Register of Controlled Trials and Central Trial Register of India were searched until September 2013. We assessed the risk of bias by Cochrane Collaboration's "risk of bias" tool. RESULTS: Two observational studies indicated feasibility ensuring coverage of population, decrease in case fatality rate in the group treated by community health workers. In an RCT, no significant difference was observed in the treatment failure rates [odds ratio (OR)=0.88], and the mortality in the first and second week (OR=1.53; OR=2.24) between gentamicin and ceftriaxone groups. Within the gentamicin group, the combination of penicillin and gentamicin showed a lower rate of treatment failure (OR=0.44) and mortality at second week of life (OR=0.17) as compared to the combination of gentamicin and oral cotrimoxazole. CONCLUSION: Gentamicin for the treatment of neonatal sepsis is both feasible and effective in community-based settings and can be used as an alternative to the hospitalbased care in resource compromised settings. But there was less evidence in the management of neonatal sepsis in hospitals as was seen in this review in which we included only one RCT and three observational studies. PMID- 26830307 TI - Establishing a relationship between clinical features and one specific type of chromosome abnormality. PMID- 26830308 TI - Prevalence of metabolic syndrome in children aged 5-9 years from southwest colombia: a cross-sectional study. AB - BACKGROUND: Exploration of cardiometabolic alterations in the pre-adolescent stage is necessary to characterize possible patterns for matabolic syndrome (MetS) in the earliest stages of the life. However, defining specific cutoff points for metabolic and vascular markers represents a complex task in pre adolescent populations. This study aimed to estimate the prevalence of MetS and its components in children aged 5-9 years old by using the MetS definition for adolescents with the lowest cut-off points, and evaluate its relationship with overweight and socio-demographic determinants. METHODS: A total of 494 children were evaluated. Multivariate models with filtered variables in preliminary univarite analyses were built to find predictive factors of MetS and its components. RESULTS: The prevalence of MetS was 8.7% in the studied children. Multivariate models showed that age, overweight and low socioeconomic stratum were associated with MetS; low high-density lipoprotein cholesterol was not significantly associated with any variable; high triglycerides were positively associated with age, overweight and inversely associated with kilocalories/day; female gender was the only variable significantly associated with high fasting glucose (inverse association); and age, gender and overweight were significant factors for increased waist circumference. In the case of high blood pressure, no variable was classified to the multivariate analysis. CONCLUSION: This study showed disturbing figures regarding cardiometabolic risk in the children based on comparisons with studies in adolescents. Further studies are needed to confirm the utility of the de Ferranti Mets definition in children. PMID- 26830309 TI - The Health Consequences of Obesity in Young Adulthood. AB - Young adults are gaining weight faster than any age group. This weight gain and the appearance of obesity-related comorbidities often commence in adolescence. Psychosocial distress and mental health issues are common and debilitating, and treatment approaches are likely to be similar to those for adolescents. At the same time, young adults may have physical morbidities which will continue and worsen throughout adulthood, such as hypertension, diabetes and polycystic ovarian syndrome. Health consequences of obesity are challenging to manage in young adults as their symptoms may be minimal, they are less likely to engage with healthcare due to other life priorities and their neurocognitive developmental stage makes therapy adherence difficult. Clinicians who manage young adults with obesity need to be aware of these age-specific challenges, as well as the sexual and reproductive health concerns that are present in this age group. PMID- 26830310 TI - A light-driven three-dimensional plasmonic nanosystem that translates molecular motion into reversible chiroptical function. AB - Nature has developed striking light-powered proteins such as bacteriorhodopsin, which can convert light energy into conformational changes for biological functions. Such natural machines are a great source of inspiration for creation of their synthetic analogues. However, synthetic molecular machines typically operate at the nanometre scale or below. Translating controlled operation of individual molecular machines to a larger dimension, for example, to 10-100 nm, which features many practical applications, is highly important but remains challenging. Here we demonstrate a light-driven plasmonic nanosystem that can amplify the molecular motion of azobenzene through the host nanostructure and consequently translate it into reversible chiroptical function with large amplitude modulation. Light is exploited as both energy source and information probe. Our plasmonic nanosystem bears unique features of optical addressability, reversibility and modulability, which are crucial for developing all-optical molecular devices with desired functionalities. PMID- 26830311 TI - Mitotic catastrophe and cancer drug resistance: A link that must to be broken. AB - An increased tendency of genomic alterations during the life cycle of cells leads to genomic instability, which is a major driving force for tumorigenesis. A considerable fraction of tumor cells are tetraploid or aneuploid, which renders them intrinsically susceptible to mitotic aberrations, and hence, are particularly sensitive to the induction of mitotic catastrophe. Resistance to cell death is also closely linked to genomic instability, as it enables malignant cells to expand even in a stressful environment. Currently it is known that cells can die via multiple mechanisms. Mitotic catastrophe represents a step preceding apoptosis or necrosis, depending on the expression and/or proper function of several proteins. Mitotic catastrophe was proposed to be an onco-suppressive mechanism and the evasion of mitotic catastrophe constitutes one of the gateways to cancer development. Thus, stimulation of mitotic catastrophe appears to be a promising strategy in cancer treatment. Indeed, several chemotherapeutic drugs are currently used at concentrations that induce apoptosis irrespective of the cell cycle phase, yet are very efficient at triggering mitotic catastrophe at lower doses, significantly limiting side effects. In the present review we summarize current data concerning the role of mitotic catastrophe in cancer drug resistance and discuss novel strategies to break this link. PMID- 26830312 TI - Treatment strategies for advanced hormone receptor-positive and human epidermal growth factor 2-negative breast cancer: the role of treatment order. AB - Although survival rates among patients with breast cancer have improved in recent years, those diagnosed with advanced disease with distant metastasis face a 5 year survival rate of less than 25%, making the management of these patients an area still in significant need of continued research. Selecting the optimal treatment order from among the variety of currently available therapy options presents a relevant challenge for medical oncologists. With the understanding that the majority of patients with breast cancer and those who succumb to this disease have HR-positive disease, this review will focus on treatment options and treatment order in patients with HR-positive advanced breast cancer. While endocrine therapy is considered the preferred treatment for first-line therapy in HR-positive/HER2-negative breast cancer, selection of the specific agent depends on the menopausal status of the patient. Palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, is also recommended as first-line treatment in patients with ER-positive/HER2-negative disease. In patients with endocrine therapy-resistant disease, specific strategies include sequencing of other antiestrogen receptor agents, or agents that target other molecular pathways. Future treatment strategies for patients with primary or secondary resistance to endocrine therapy for advanced disease are discussed. These strategies include first-line therapy with high-dose fulvestrant or everolimus (in combination with exemestane or letrozole or with other endocrine therapies), use of the PI3K inhibitors (e.g., buparlisib, alpelisib, pictilisib, taselisib), entinostat, CDK 4/6 inhibitors (e.g., palbociclib, ribociclib, abemaciclib), and novel selective estrogen receptor degradation agents that may enhance the targeting of acquired mutations in the ESR1 gene. PMID- 26830313 TI - Lysosomes as mediators of drug resistance in cancer. AB - Drug resistance remains a leading cause of chemotherapeutic treatment failure and cancer-related mortality. While some mechanisms of anticancer drug resistance have been well characterized, multiple mechanisms remain elusive. In this respect, passive ion trapping-based lysosomal sequestration of multiple hydrophobic weak-base chemotherapeutic agents was found to reduce the accessibility of these drugs to their target sites, resulting in a markedly reduced cytotoxic effect and drug resistance. Recently we have demonstrated that lysosomal sequestration of hydrophobic weak base drugs triggers TFEB-mediated lysosomal biogenesis resulting in an enlarged lysosomal compartment, capable of enhanced drug sequestration. This study further showed that cancer cells with an increased number of drug-accumulating lysosomes are more resistant to lysosome sequestered drugs, suggesting a model of drug-induced lysosome-mediated chemoresistance. In addition to passive drug sequestration of hydrophobic weak base chemotherapeutics, other mechanisms of lysosome-mediated drug resistance have also been reported; these include active lysosomal drug sequestration mediated by ATP-driven transporters from the ABC superfamily, and a role for lysosomal copper transporters in cancer resistance to platinum-based chemotherapeutics. Furthermore, lysosomal exocytosis was suggested as a mechanism to facilitate the clearance of chemotherapeutics which highly accumulated in lysosomes, thus providing an additional line of resistance, supplementing the organelle entrapment of chemotherapeutics away from their target sites. Along with these mechanisms of lysosome-mediated drug resistance, several approaches were recently developed for the overcoming of drug resistance or exploiting lysosomal drug sequestration, including lysosomal photodestruction and drug induced lysosomal membrane permeabilization. In this review we explore the current literature addressing the role of lysosomes in mediating cancer drug resistance as well as novel modalities to overcome this chemoresistance. PMID- 26830314 TI - Mechanisms of cisplatin resistance and targeting of cancer stem cells: Adding glycosylation to the equation. AB - Cisplatin-based chemotherapeutic regimens are the most frequently used (neo)adjuvant treatments for the majority of solid tumors. While platinum-based chemotherapeutic regimens have proven effective against highly proliferative malignant tumors, significant relapse and progression rates as well as decreased overall survival are still observed. Currently, it is known that sub-populations of chemoresistant cells share biological properties with cancer stem cells (CSC), which are believed to be responsible for tumor relapse, invasion and ultimately disease dissemination through acquisition of mesenchymal cell traits. In spite of concentrated efforts devoted to decipher the mechanisms underlying CSC chemoresistance and to design targeted therapeutics to these cells, proteomics has failed to unveil molecular signatures capable of distinguishing between malignant and non-malignant stem cells. This has hampered substantial developments in this complex field. Envisaging a novel rationale for an effective therapy, the current review summarizes the main cellular and molecular mechanisms underlying cisplatin resistance and the impact of chemotherapy challenge in CSC selection and clinical outcome. It further emphasizes the growing amount of data supporting a role for protein glycosylation in drug resistance. The dynamic and context-dependent nature of protein glycosylation is also comprehensively discussed, hence highlighting its potentially important role as a biomarker of CSC. As the paradigm of cancer therapeutics shifts towards precision medicine and patient-tailored therapeutics, we bring into focus the need to introduce glycomics and glycoproteomics in holistic pan-omics models, in order to integrate diverse, multimodal and clinically relevant information towards more effective cancer therapeutics. PMID- 26830315 TI - Studying platinum sensitivity and resistance in high-grade serous ovarian cancer: Different models for different questions. AB - High-grade serous ovarian cancer (HGSOC) has the highest mortality rate among all gynecological cancers. Patients are generally diagnosed in an advanced stage with the majority of cases displaying platinum resistant relapses. Recent genomic interrogation of large numbers of HGSOC patient samples indicated high complexity in terms of genetic aberrations, intra- and intertumor heterogeneity and underscored their lack of targetable oncogenic mutations. Sub-classifications of HGSOC based on expression profiles, termed 'differentiated', 'immunoreactive', 'mesenchymal' and 'proliferative', were shown to have prognostic value. In addition, in almost half of all HGSOC patients, a deficiency in homologous recombination (HR) was found that potentially can be targeted using PARP inhibitors. Developing precision medicine requires advanced experimental models. In the current review, we discuss experimental HGSOC models in which resistance to platinum therapy and the use of novel therapeutics can be carefully studied. Panels of better-defined primary cell lines need to be established to capture the full spectrum of HGSOC subtypes. Further refinement of cell lines is obtained with a 3-dimensional culture model mimicking the tumor microenvironment. Alternatively, ex vivo ovarian tumor tissue slices are used. For in vivo studies, larger panels of ovarian cancer patient-derived xenografts (PDXs) are being established, encompassing all expression subtypes. Ovarian cancer PDXs grossly retain tumor heterogeneity and clinical response to platinum therapy is preserved. PDXs are currently used in drug screens and as avatars for patient response. The role of the immune system in tumor responses can be assessed using humanized PDXs and immunocompetent genetically engineered mouse models. Dynamic tracking of genetic alterations in PDXs as well as patients during treatment and after relapse is feasible by sequencing circulating cell-free tumor DNA and analyzing circulating tumor cells. We discuss how various models and methods can be combined to delineate the molecular mechanisms underlying platinum resistance and to select HGSOC patients other than BRCA1/2-mutation carriers that could potentially benefit from the synthetic lethality of PARP inhibitors. This integrated approach is a first step to improve therapy outcomes in specific subgroups of HGSOC patients. PMID- 26830316 TI - Complex Greenland outlet glacier flow captured. AB - The Greenland Ice Sheet is losing mass at an accelerating rate due to increased surface melt and flow acceleration in outlet glaciers. Quantifying future dynamic contributions to sea level requires accurate portrayal of outlet glaciers in ice sheet simulations, but to date poor knowledge of subglacial topography and limited model resolution have prevented reproduction of complex spatial patterns of outlet flow. Here we combine a high-resolution ice-sheet model coupled to uniformly applied models of subglacial hydrology and basal sliding, and a new subglacial topography data set to simulate the flow of the Greenland Ice Sheet. Flow patterns of many outlet glaciers are well captured, illustrating fundamental commonalities in outlet glacier flow and highlighting the importance of efforts to map subglacial topography. Success in reproducing present day flow patterns shows the potential for prognostic modelling of ice sheets without the need for spatially varying parameters with uncertain time evolution. PMID- 26830317 TI - Serum Calcium and Phosphate Levels and Short- and Long-Term Outcomes in Acute Intracerebral Hemorrhage Patients. AB - BACKGROUND: We investigated whether admission serum calcium and phosphate levels are associated with short- and long-term outcomes in patients with acute intracerebral hemorrhage. METHODS: A total of 365 patients with acute intracerebral hemorrhage were enrolled in this study. Participants were classified into 4 subgroups according to serum calcium or phosphate quartiles. Demographic characteristics, lifestyle risk factors, medical history, and other clinical characteristics were recorded for all the participants. Excellent outcome was defined as discharge or 3-month modified Rankin scale scores of 0-1. RESULTS: Univariate analysis comparing the highest and lowest quartiles indicated that an elevated calcium level was associated with 2.26- and 2.28-fold increases in the odds for discharge and 3-month excellent outcome, respectively. After adjustment for age, sex, and other potential risk factors, patients in the highest quartile still had significantly increased odds of discharge and 3-month excellent outcome; the corresponding odds ratios (ORs) were 3.43 (95% confidence interval [[CI], 1.03-11.44) and 5.36 (95% CI, 1.69-16.98). When calcium was divided into two groups, the ORs of higher calcium were 2.9 (95% CI, 1.1-7.62) and 2.8 (95% CI, 1.15-6.82) for discharge and 3-month excellent outcome, respectively. However, no significant association was observed between serum phosphate and excellent outcome. CONCLUSIONS: Elevated admission serum calcium level but not phosphate level is positively associated with excellent outcome at discharge or 3 months in acute intracerebral hemorrhage patients. PMID- 26830318 TI - The association between cognitive deficits and prefrontal hemodynamic responses during performance of working memory task in patients with schizophrenia. AB - Schizophrenia-associated cognitive deficits are resistant to treatment and thus pose a lifelong burden. The Brief Assessment of Cognition in Schizophrenia (BACS) provides reliable and valid assessments across cognitive domains. However, because the prefrontal functional abnormalities specifically associated with the level of cognitive deficits in schizophrenia have not been examined, we explored this relationship. Patients with schizophrenia (N=87) and matched healthy controls (N=50) participated in the study. Using near-infrared spectroscopy (NIRS), we measured the hemodynamic responses in the prefrontal and superior temporal cortical surface areas during a working memory task. Correlation analyses revealed a relationship between the hemodynamics and the BACS composite and domain scores. Hemodynamic responses of the left dorsolateral prefrontal cortex (DLPFC) and left frontopolar cortex (FPC) in the higher-level-of-cognitive function schizophrenia group were weaker than the responses of the controls but similar to those of the lower-level-of-cognitive-function schizophrenia group. However, hemodynamic responses in the right DLPFC, bilateral ventrolateral PFC (VLPFC), and right temporal regions decreased with increasing cognitive deficits. In addition, the hemodynamic response correlated positively with the level of cognitive function (BACS composite scores) in the right DLPFC, bilateral VLPFC, right FPC, and bilateral temporal regions in schizophrenia. The correlation was driven by all BACS domains. Our results suggest that the linked functional deficits in the right DLPFC, bilateral VLPFC, right FPC, and bilateral temporal regions may be related to BACS-measured cognitive impairments in schizophrenia and show that linking the neurocognitive deficits and brain abnormalities can increase our understanding of schizophrenia pathophysiology. PMID- 26830319 TI - Maternal immune activation alters glutamic acid decarboxylase-67 expression in the brains of adult rat offspring. AB - Activation of the maternal innate immune system, termed "maternal immune activation" (MIA), represents a common environmental risk factor for schizophrenia. Whereas evidence suggests dysregulation of GABA systems may underlie the pathophysiology of schizophrenia, a role for MIA in alteration of GABAergic systems is less clear. Here, pregnant rats received either the viral mimetic polyriboinosinic-polyribocytidilic acid or vehicle injection on gestational day 14. Glutamic acid decarboxylase-67 (GAD67) mRNA expression was examined in male offspring at postnatal day (P)14, P30 and P60. At P60, GAD67 mRNA was elevated in hippocampus and thalamus and decreased in prefrontal cortex of MIA offspring. MIA-induced alterations in GAD expression could contribute to the pathophysiology of schizophrenia. PMID- 26830320 TI - Lack of association between IL-10 and IL-18 gene promoter polymorphisms and Parkinson's disease with cognitive impairment in a Chinese population. AB - Inflammatory processes have been implicated in the pathogenesis of Parkinson's disease (PD), including the development of PD-associated cognitive impairment. Whether genetic variants of inflammatory cytokine genes influence the risk of cognitive impairment in PD is unknown. In this study, we investigated single nucleotide polymorphisms (SNPs) in the IL-10 promoter (rs1800871 and rs1800872) and in the IL-18 promoter (rs1946518 and rs187238) in a Han Chinese cohort (N = 933). PD patients (N = 460) and controls (N = 473) were genotyped. Additionally, 268 PD patients were divided into three subgroups [cognitively normal (PD-NC), mild cognitive impairment (PD-MCI), and with dementia (PD-D)] on the basis of their performance on a battery of neuropsychological tests. No associations were found between the aforementioned polymorphisms and cognitive impairment in PD; thus no confirmatory evidence for the hypothesis of IL-10 and IL-18 alleles modulating the risk of cognitive impairment in Chinese PD patients was obtained. PMID- 26830321 TI - To senesce or not to senesce: how primary human fibroblasts decide their cell fate after DNA damage. AB - Excessive DNA damage can induce an irreversible cell cycle arrest, called senescence, which is generally perceived as an important tumour-suppressor mechanism. However, it is unclear how cells decide whether to senesce or not after DNA damage. By combining experimental data with a parameterized mathematical model we elucidate this cell fate decision at the G1-S transition. Our model provides a quantitative and conceptually new understanding of how human fibroblasts decide whether DNA damage is beyond repair and senesce. Model and data imply that the G1-S transition is regulated by a bistable hysteresis switch with respect to Cdk2 activity, which in turn is controlled by the Cdk2/p21 ratio rather than cyclin abundance. We experimentally confirm the resulting predictions that to induce senescence i) in healthy cells both high initial and elevated background DNA damage are necessary and sufficient, and ii) in already damaged cells much lower additional DNA damage is sufficient. Our study provides a mechanistic explanation of a) how noise in protein abundances allows cells to overcome the G1-S arrest even with substantial DNA damage, potentially leading to neoplasia, and b) how accumulating DNA damage with age increasingly sensitizes cells for senescence. PMID- 26830323 TI - Universal anyons at the irradiated surface of topological insulator. AB - Anyons have recently received great attention due to their promising application in topological quantum computation. The best validated system that enjoys the anyonic excitations are the Laughlin states. The quasi-particles in Laughlin states are neither fermions nor bosons but possess the discrete statistical angle theta = pi/m, with m being an integer. Here we report a possible realization of the universal Abelian anyons, whose statistical angle can be tuned continuously by external parameters and can take any arbitrary values interpolating theta = 0 and theta = pi. The proposed setup is the surface state of a three dimensional topological insulator driven by an amplitude-modulated circularly-polarized light. It is found that the external field leads to a particular Floquet phase, which is a two-spatial-dimensional analogy of the Weyl semimetal phase in the Floquet first Brillouin zone. The chiral anomaly of this phase results in a U(1) Chern-Simons gauge theory with a tunable Floquet Chern number. Owing to this underlying gauge field theory, the irradiated surface of topological insulator constitutes a promising platform for the observation of the universal anyons. PMID- 26830322 TI - The promoter methylomes of monochorionic twin placentas reveal intrauterine growth restriction-specific variations in the methylation patterns. AB - Intrauterine growth restriction (IUGR) affects the foetus and has a number of pathological consequences throughout life. Recent work has indicated that variations in DNA methylation might cause placental dysfunction, which may be associated with adverse pregnancy complications. Here, we investigated the promoter methylomes of placental shares from seven monochorionic (MC) twins with selective intrauterine growth restriction (sIUGR) using the healthy twin as an ideal control. Our work demonstrated that the IUGR placental shares harboured a distinct DNA hypomethylation pattern and that the methylation variations preferentially occurred in CpG island shores or non-CpG island promoters. The differentially methylated promoters could significantly separate the IUGR placental shares from the healthy ones. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) further confirmed the genome wide DNA hypomethylation and the lower level of hydroxymethylation statuses in the IUGR placental shares. The methylation variations of the LRAT and SLC19A1 promoters, which are involved in vitamin A metabolism and folate transportation, respectively, and the EFS promoter were further validated in an additional 12 pairs of MC twins with sIUGR. Although the expressions of LRAT, SLC19A1 and EFS were not affected, we still speculated that DNA methylation and hydroxymethylation might serve a functional role during in utero foetal development. PMID- 26830324 TI - Knockin of Cre Gene at Ins2 Locus Reveals No Cre Activity in Mouse Hypothalamic Neurons. AB - The recombination efficiency and cell specificity of Cre driver lines are critical for exploring pancreatic beta cell biology with the Cre/LoxP approach. Some commonly used Cre lines are based on the short Ins2 promoter fragment and show recombination activity in hypothalamic neurons; however, whether this stems from endogenous Ins2 promoter activity remains controversial. In this study, we generated Ins2-Cre knockin mice with a targeted insertion of IRES-Cre at the Ins2 locus and demonstrated with a cell lineage tracing study that the Ins2 gene is not transcriptionally active in the hypothalamus. The Ins2-Cre driver line displayed robust Cre expression and activity in pancreatic beta cells without significant alterations in insulin expression. In the brain, Cre activity was mainly restricted to the choroid plexus, without significant recombination detected in the hippocampus or hypothalamus by the LacZ or fluorescent tdTomato reporters. Furthermore, Ins2-Cre mice exhibited normal glucose tolerance and insulin secretion upon glucose stimulation in vivo. In conclusion, this Ins2-Cre driver line allowed high-fidelity detection of endogenous Ins2 promoter activity in vivo, and the negative activity in the hypothalamus demonstrated that this system is a promising alternative tool for studying beta cell biology. PMID- 26830325 TI - Nonvolatile modulation of electronic structure and correlative magnetism of L10 FePt films using significant strain induced by shape memory substrates. AB - Tuning the lattice strain (epsilonL) is a novel approach to manipulate the magnetic, electronic, and transport properties of spintronic materials. Achievable epsilonL in thin film samples induced by traditional ferroelectric or flexible substrates is usually volatile and well below 1%. Such limits in the tuning capability cannot meet the requirements for nonvolatile applications of spintronic materials. This study answers to the challenge of introducing significant amount of elastic strain in deposited thin films so that noticeable tuning of the spintronic characteristics can be realized. Based on subtle elastic strain engineering of depositing L10-FePt films on pre-stretched NiTi(Nb) shape memory alloy substrates, steerable and nonvolatile lattice strain up to 2.18% has been achieved in the L10-FePt films by thermally controlling the shape memory effect of the substrates. Introduced strains at this level significantly modify the electronic density of state, orbital overlap, and spin-orbit coupling (SOC) strength in the FePt film, leading to nonvolatile modulation of magnetic anisotropy and magnetization reversal characteristics. This finding not only opens an efficient avenue for the nonvolatile tuning of SOC based magnetism and spintronic effects, but also helps to clarify the physical nature of pure strain effect. PMID- 26830326 TI - A universal probe design for colorimetric detection of single-nucleotide variation with visible readout and high specificity. AB - Single-nucleotide variation (SNV) is a crucial biomarker for drug resistance related detection in cancer and bacterial infection. However, the unintended binding of DNA probes limits the specificity of SNV detection, and the need for redesigned sequences compromise the universality of SNV assay. Herein, we demonstrated a universal and low-cost assay for the colorimetric discrimination of drug-resistance related point mutation. By the use of a universal DNA probe and a split G-quadruplex, the signal could be recognized by naked eye at room temperature. The DNA probe was used as a signal reporter which not only improved the universality, but also enabled high specificity of probe hybridization. This assay was successfully applied in the detection of cancer-related SNV in the epidermal growth factor receptor (EGFR) gene, kirsten rat sarcoma viral oncogene homologue (KRAS), and tuberculosis drug-resistance related point mutation in RNA polymerase beta subunit gene (rpoB) with high specificity and visible readout. This method was simple, rapid, high-throughput and effective, which was suitable for point-of-care applications. PMID- 26830327 TI - John Delwyn Thomas. PMID- 26830328 TI - Obstructive lung function decline and IPF: The dark face of the moon. PMID- 26830329 TI - Characterization of human follicular thyroid cancer cell lines in preclinical mouse models. AB - Follicular thyroid cancer (FTC) is the second most common type of thyroid cancers. In order to develop more effective personalized therapies, it is necessary to thoroughly evaluate patient-derived cell lines in in vivo preclinical models before using them to test new, targeted therapies. This study evaluates the tumorigenic and metastatic potential of a panel of three human FTC cell lines (WRO, FTC-238, and TT1609-CO2) with defined genetic mutations in two in vivo murine models: an orthotopic thyroid cancer model to study tumor progression and a tail vein injection model to study metastasis. All cell lines developed tumors in the orthotopic model, with take rates of 100%. Notably, WRO derived tumors grew two to four times faster than tumors arising from the FTC-238 and TT2609-CO2 cell lines. These results mirrored those of a tail vein injection model for lung metastasis: one hundred percent of mice injected with WRO cells in the tail vein exhibited aggressive growth of bilateral lung metastases within 35 days. In contrast, tail vein injection of FTC-238 or TT2609-CO2 cells did not result in lung metastasis. Together, our work demonstrates that these human FTC cell lines display highly varied tumorigenic and metastatic potential in vivo with WRO being the most aggressive cell line in both orthotopic and lung metastasis models. This information will be valuable when selecting cell lines for preclinical drug testing. PMID- 26830330 TI - Tinselenidene: a Two-dimensional Auxetic Material with Ultralow Lattice Thermal Conductivity and Ultrahigh Hole Mobility. AB - By means of extensive ab initio calculations, a new two-dimensional (2D) atomic material tin selenide monolayer (coined as tinselenidene) is predicted to be a semiconductor with an indirect gap (~1.45 eV) and a high hole mobility (of order 10000 cm(2)V(-1)S(-1)), and will bear an indirect-direct gap transition under a rather low strain (<0.5 GPa). Tinselenidene has a very small Young's modulus (20 40 GPa) and an ultralow lattice thermal conductivity (<3 Wm(-1)K(-1) at 300 K), making it probably the most flexible and most heat-insulating material in known 2D atomic materials. In addition, tinseleniden has a large negative Poisson's ratio of -0.17, thus could act as a 2D auxetic material. With these intriguing properties, tinselenidene could have wide potential applications in thermoelectrics, nanomechanics and optoelectronics. PMID- 26830331 TI - Loop replacements with gut-binding peptides in Cry1Ab domain II enhanced toxicity against the brown planthopper, Nilaparvata lugens (Stal). AB - Bacillus thuringiensis (Bt) Cry toxins have been used widely in pest managements. However, Cry toxins are not effective against sap-sucking insects (Hemiptera), which limits the application of Bt for pest management. In order to extend the insecticidal spectrum of Bt toxins to the rice brown planthopper (BPH), Nilaparvata lugens, we modified Cry1Ab putative receptor binding domains with selected BPH gut-binding peptides (GBPs). Three surface exposed loops in the domain II of Cry1Ab were replaced with two GBPs (P2S and P1Z) respectively. Bioassay results showed that toxicity of modified toxin L2-P2S increased significantly (~9 folds) against BPH nymphs. In addition, damage of midgut cells was observed from the nymphs fed with L2-P2S. Our results indicate that modifying Cry toxins based on the toxin-gut interactions can broaden the insecticidal spectrum of Bt toxin. This method provides another approach for the development of transgenic crops with novel insecticidal activity against hemipteran insects and insect populations resistant to current Bt transgenic crops. PMID- 26830332 TI - Non-T cell activation linker (NTAL) proteolytic cleavage as a terminator of activatory intracellular signals. AB - Non-T cell activation linker is an adaptor protein that is tyrosine phosphorylated upon cross-linking of immune receptors expressed on B lymphocytes, NK cells, macrophages, basophils, or mast cells, allowing the recruitment of cytosolic mediators for downstream signaling pathways. Fas receptor acts mainly as a death receptor, and when cross-linked with Fas ligand, many proteins are proteolytically cleaved, including several signaling molecules in T and B cells. Fas receptor triggering also interferes with TCR intracellular signals, probably by means of proteolytic cleavage of several adaptor proteins. We have previously found that the adaptor linker for activation of T cells, evolutionarily related to non-T cell activation linker, is cleaved upon proapoptotic stimuli in T lymphocytes and thymocytes, in a tyrosine phosphorylation-dependent fashion. Here, we describe non-T cell activation linker proteolytic cleavage triggered in human B cells and monocytes by Fas cross-linking and staurosporine treatment. Non T cell activation linker is cleaved, producing an N-terminal fragment of ~22 kDa, and such cleavage is abrogated in the presence of caspase 8/granzyme B and caspase 3 inhibitors. Moreover, we have identified an aspartic acid residue at which non-T cell activation linker is cleaved, which similar to linker for activation of T cells, this aspartic acid residue is located close to tyrosine and serine residues, suggesting an interdependence of phosphorylation and proteolytic cleavage. Consistently, induction of non-T cell activation linker phosphorylation by pervanadate inhibits its cleavage. Interestingly, the truncated isoform of non-T cell activation linker, generated after cleavage, has a decreased signaling ability when compared with the full-length molecule. Altogether, our results suggest that cleavage of transmembrane adaptors constitutes a general mechanism for signal termination of immune receptors. PMID- 26830333 TI - Aged garlic extract and S-allylcysteine prevent apoptotic cell death in a chemical hypoxia model. AB - BACKGROUND: Aged garlic extract (AGE) and its main constituent S-allylcysteine (SAC) are natural antioxidants with protective effects against cerebral ischemia or cancer, events that involve hypoxia stress. Cobalt chloride (CoCl2) has been used to mimic hypoxic conditions through the stabilization of the alpha subunit of hypoxia inducible factor (HIF-1alpha) and up-regulation of HIF-1alpha dependent genes as well as activation of hypoxic conditions such as reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential and apoptosis. The present study was designed to assess the effect of AGE and SAC on the CoCl2-chemical hypoxia model in PC12 cells. RESULTS: We found that CoCl2 induced the stabilization of HIF-1alpha and its nuclear localization. CoCl2 produced ROS and apoptotic cell death that depended on hypoxia extent. The treatment with AGE and SAC decreased ROS and protected against CoCl2-induced apoptotic cell death which depended on the CoCl2 concentration and incubation time. SAC or AGE decreased the number of cells in the early and late stages of apoptosis. Interestingly, this protective effect was associated with attenuation in HIF-1alpha stabilization, activity not previously reported for AGE and SAC. CONCLUSIONS: Obtained results show that AGE and SAC decreased apoptotic CoCl2 induced cell death. This protection occurs by affecting the activity of HIF 1alpha and supports the use of these natural compounds as a therapeutic alternative for hypoxic conditions. PMID- 26830334 TI - Measurement of ex vivo ELISpot interferon-gamma recall responses to Plasmodium falciparum AMA1 and CSP in Ghanaian adults with natural exposure to malaria. AB - BACKGROUND: Malaria eradication requires a concerted approach involving all available control tools, and an effective vaccine would complement these efforts. An effective malaria vaccine should be able to induce protective immune responses in a genetically diverse population. Identification of immunodominant T cell epitopes will assist in determining if candidate vaccines will be immunogenic in malaria-endemic areas. This study therefore investigated whether class I restricted T cell epitopes of two leading malaria vaccine antigens, Plasmodium falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1), could recall T cell interferon-gamma responses from naturally exposed subjects using ex vivo ELISpot assays. METHODS: Thirty-five subjects aged between 24 and 43 years were recruited from a malaria-endemic urban community of Ghana in 2011, and their peripheral blood mononuclear cells (PBMCs) were tested in ELISpot IFN gamma assays against overlapping 15mer peptide pools spanning the entire CSP and AMA1 antigens, and 9-10mer peptide epitope mixtures that included previously identified and/or predicted human leukocyte antigen (HLA) class 1-restricted epitopes from same two antigens. RESULTS: For CSP, 26 % of subjects responded to at least one of the nine 15mer peptide pools whilst 17 % responded to at least one of the five 9-10mer HLA-restricted epitope mixtures. For AMA1, 63 % of subjects responded to at least one of the 12 AMA1 15mer peptide pools and 51 % responded to at least one of the six 9-10mer HLA-restricted epitope mixtures. Following analysis of data from the two sets of peptide pools, along with bioinformatics predictions of class I-restricted epitopes and the HLA supertypes expressed by a subset of study subjects, peptide pools that may contain epitopes recognized by multiple HLA supertypes were identified. Collectively, these results suggest that natural transmission elicits ELISpot IFN-gamma activities to class 1-restricted epitopes that are largely HLA-promiscuous. CONCLUSIONS: These results generally demonstrate that CSP and AMA1 peptides recalled ELISpot IFN gamma responses from naturally exposed individuals and that both CSP and AMA1 contain diverse class 1-restricted epitopes that are HLA-promiscuous and are widely recognized in this population. PMID- 26830335 TI - Lessons from a French collaborative case-control study in cystic fibrosis patients during the 2009 A/H1N1 influenza pandemy. AB - BACKGROUND: Viral infections such as influenza are thought to impact respiratory parameters and to promote infection with Pseudomonas aeruginosa in patients with cystic fibrosis (CF). However, the real morbidity of the influenza virus in CF needs to be further investigated because previous studies were only observational. METHODS: CF patients were included in a case-control study (n = 44 cases and n = 371 controls) during the 2009 pandemic A/H1N1 influenza. Cases were patients with polymerase reaction chain-confirmed influenza A/H1N1 infection. Controls did not report any influenza symptoms during the same period. Sputum colonization and lung function were monitored during 1 year after inclusion. RESULTS: Cases were significantly younger than controls (mean(SD) 14.9 years(11) versus 20.1 years (13.2) and significantly less frequently colonized with P. aeruginosa (34 % versus 53 %). During influenza infection, 74 % of cases had pulmonary exacerbation, 92 % had antibiotics adapted to their usual sputum colonization and 82 % were treated with oseltamivir. Two cases required lung transplantation after A/H1N1 infection (one had not received oseltamivir and the other one had been treated late). The cases received a mean number of antibiotic treatments significantly higher during the year after the influenza infection (mean(SD) 2.8 (2.4) for cases versus 1.8(2.1) for controls; p = 0.002). An age matched comparison did not demonstrate any significant modification of bronchopulmonary bacterial colonization during the year after influenza infection nor any significant change in FEV1 at months 1, 3 and 12 after A/H1N1 infection. CONCLUSIONS: Our results do not demonstrate any change in sputum colonization nor significant lung disease progression after pandemic A/H1N1 influenza. TRIAL REGISTRATION: Clinical Trials.gov registration number: NCT01499914. PMID- 26830336 TI - Hospital admissions from a pediatric HIV care and treatment program in Malawi. AB - BACKGROUND: The scale up of pediatric antiretroviral treatment programs across Sub-Saharan Africa over the last decade has brought increasing numbers of children into HIV care. This patient population requiring life-long care presents new challenges in the outpatient and inpatient settings. We sought to describe hospitalizations from a large pediatric HIV treatment facility to better understand the scope of the situation and identify areas for improved care delivery. METHODS: We conducted a retrospective case series of all HIV-infected and exposed patients <18 years enrolled at Baylor College of Medicine Children's Foundation Malawi, from October 2004-October 2010. Patients admitted to the hospital on or after the day of enrollment were included. Data were extracted from electronic clinic records. Analysis was done at the patient and admission level, as some patients had multiple admissions. RESULTS: Of 5062 patients enrolled in care, 877 (17.3 %) had 1137 admissions at median age 24 months (IQR: 12-62). 191 (21.8 %) patients had multiple admissions. A high proportion of admissions occurred in patients under two years (49.4 %), those within one month of clinic enrollment (32.9 %), those with severe immune suppression (44.0 %), and those not on ART (48.5 %). The frequency of primary admission diagnoses varied across these same variables, with malnutrition, pneumonia, and malaria being the most common. CONCLUSIONS: Illness requiring hospitalization is common in HIV infected and exposed children and these results reinforce the need for a comprehensive care package with special attention to nutrition. Strengthened programs for malaria prevention and expanded access to pneumococcal vaccine are also needed. The high burden of admissions in children under 24 months and those newly enrolled in care suggests a need for continued improvement of early infant diagnosis and provider-initiated testing programs to link patients to care before they are symptomatic. Similarly, the high proportion of admissions in those not yet started on ART emphasizes the importance of rapid initiation of ART for eligible pediatric patients. PMID- 26830337 TI - Could university training and a proactive attitude of coworkers be associated with influenza vaccination compliance? A multicentre survey among Italian medical residents. AB - BACKGROUND: Although influenza vaccination has been demonstrated to be safe and effective, vaccination coverage rates among health care workers and among medical residents appear generally low. Several investigations have been performed worldwide to analyze the healthcare workers' educational deficiencies. This multicentre survey aimed to investigate at a nationwide level training quality and work environment associated with seasonal influenza vaccination uptake among Italian medical residents. METHODS: A retrospective cohort study was carried out from April 2012 to June 2012 on medical residents regularly attending the post graduate medical schools of 18 Italian Universities via an anonymous, self administered, web-based questionnaire. Data have been analyzed by using the R statistical software package. RESULTS: A total of 2506 out of 10,854 medical residents (23.1%) have been recruited. The quality of training on influenza and influenza vaccination was reported as "fair" or "poor" during both pre-graduate (40.7% of respondents) and post-graduate medical school (59.6% of respondents). Vaccination uptake was associated with adherence to seasonal 2011/2012 influenza vaccination of medical school tutors (adjusted OR = 4.4; 95% CI = 1.35-14.26) and other medical residents (adjusted OR = 2.2; 95% CI = 1.14-4.23). Moreover, influenza vaccination uptake was also associated with correct knowledge about the virus composition of 2011/2012 influenza vaccine (adjusted OR = 2.43; 95% CI = 1.64-2.58) and consultation of scientific sources or Institutional recommendations on influenza vaccination (adjusted OR = 6.96; 95% CI = 3.38 214.36). CONCLUSIONS: Medical residency represents an opportunity to implement educational and training interventions aiming to promote appropriate professional behaviors and skills. Our study suggest that appropriate training, adequate education and proactive coworkers feelings can improve influenza vaccination attitudes towards young doctor. PMID- 26830338 TI - Quantitatively Predict the Potential of MnO2 Polymorphs as Magnesium Battery Cathodes. AB - Despite tremendous efforts denoted to magnesium battery research, the realization of magnesium battery is still challenged by the lack of cathode candidate with high energy density, rate capability and good recyclability. This situation can be largely attributed to the failure to achieve sustainable magnesium intercalation chemistry. In current work we explored the magnesiation of distinct MnO2 polymorphs using first-principles calculations, focusing on providing quantitative analysis about the feasibility of magnesium intercalation. Consistent with experimental observations, we predicted that ramsdellite-MnO2 and alpha-MnO2 are conversion-type cathodes while nanosized spinel-MnO2 and MnO2 isostructual to CaFe2O4 are better candidates for Mg intercalation. Key properties that restrict Mg intercalation include not only sluggish Mg migration but also stronger distortion that damages structure integrity and undesirable conversion reaction. We demonstrate that by evaluating the reaction free energy, structural deformation associated with the insertion of magnesium, and the diffusion barriers, a quantitative evaluation about the feasibility of magnesium intercalation can be well established. Although our current work focuses on the study of MnO2 polymorphs, the same evaluation can be applied to other cathode candidates, thus paving the road to identify better cathode candidates in future. PMID- 26830339 TI - Letter to the editor: Angiotensin quantification by mass spectrometry. PMID- 26830340 TI - Reply to "Letter to the editor: Angiotensin quantification by mass spectrometry". PMID- 26830341 TI - Screening for rheumatic heart disease: quality and agreement of focused cardiac ultrasound by briefly trained health workers. AB - BACKGROUND: Echocardiographic screening for rheumatic heart disease (RHD) has the potential to detect subclinical cases for secondary prevention, but is constrained by inadequate human resources in most settings. Training non-expert health workers to perform focused cardiac ultrasound (FoCUS) may enable screening at a population-level. We aimed to evaluate the quality and agreement of FoCUS for valvular regurgitation by briefly trained health workers. METHODS: Seven nurses participated in an eight week training program in Fiji. Nurses performed FoCUS on 2018 children aged five to 15 years, and assessed any valvular regurgitation. An experienced pediatric cardiologist assessed the quality of ultrasound images and measured any recorded regurgitation. The assessment of the presence of regurgitation and measurement of the longest jet by the nurse and cardiologist was compared, using the Bland-Altman method. RESULTS: The quality of FoCUS overall was adequate for diagnosis in 96.6%. There was substantial agreement between the cardiologist and the nurses overall on the presence of mitral regurgitation (kappa = 0.75) and aortic regurgitation (kappa = 0.61) seen in two views. Measurements of mitral regurgitation by nurses and the cardiologist were similar (mean bias 0.01 cm; 95% limits of agreement -0.64 to 0.66 cm). CONCLUSIONS: After brief training, health workers with no prior experience in echocardiography can obtain adequate quality images and make a reliable assessment on the presence and extent of valvular regurgitation. Further evaluation of the imaging performance and accuracy of screening by non-expert operators is warranted, as a potential population-level screening strategy in high prevalence settings. PMID- 26830342 TI - Fabrication of a Micellar Supramolecular Hydrogel for Ocular Drug Delivery. AB - In this paper, we describe a simple method for constructing a micellar supramolecular hydrogel, composed of a low-molecular-weight methoxy poly(ethylene glycol) (Mn = 2000 Da) block polymer and alpha-cyclodextrin (alpha-CD), for topical ocular drug delivery. Adding aqueous block polymer micelles into an alpha CD aqueous solution resulted in the formation of a micellar supramolecular hydrogel through host-guest inclusion. The effects of the drug payload, block polymer, and alpha-CD concentrations as well as the block polymer structure on gelation time were investigated. The resultant micellar supramolecular hydrogels were thoroughly characterized by X-ray diffraction, rheological studies, and scanning electron microscopy. The hydrogels exhibited thixotropic properties, which are beneficial to ocular drug delivery. In vitro release studies indicated that the alpha-CD concentration strongly influenced the release rate of diclofenac (DIC) from supramolecular hydrogel. The hydrogels showed relatively low cytotoxicity toward L-929 and HCEC cells and did not significantly affect the migration of the latter after 24 h incubation. The hydrogel was nonirritant toward the rabbit eye, as indicated by the Draize test, fluorescein staining, and histological observation. Nile Red-labeled micellar supramolecular hydrogel showed that it could significantly extend the retention time on the corneal surface in rabbits, compared with a plain micellar formulation. In vivo pharmacokinetics indicated that the hydrogel could greatly improve ocular drug bioavailability, compared with that of micellar formulation. Our results suggest that the micellar supramolecular hydrogel is a promising system for ocular drug delivery. PMID- 26830343 TI - Missouri K-12 school collection and reporting of school-based syndromic surveillance data: a cross sectional study. AB - BACKGROUND: School participation in collecting and reporting syndromic surveillance (SS) data to public health officials and school nurses' attitudes regarding SS have not been assessed. METHODS: An online survey was sent to Missouri Association of School Nurses members during the 2013/2014 school year to assess whether K-12 schools were collecting and reporting SS data. Z-scores were used to assess collection versus reporting of SS indicators. Logistic regressions were used to describe factors predicting nurses' collection and reporting of SS indicators: all-cause absenteeism, influenza-like illness and gastrointestinal illness. Univariate predictors were assessed with Chi-Squares. RESULTS: In total, 133 school nurses participated (33.6 % response rate). Almost all (90.2 %, n = 120) collect at least one SS indicator; half (49.6 %, n = 66) report at least one. Schools are collecting more SS data than they are reporting to the health department (p < .05 for all comparisons). Determinants of school nurses' collection of SS data included perceived administrative support, and knowledge of collecting and analyzing SS data. The strongest predictive factors for reporting SS data were the perception that the health department was interested in SS data and being approached by the health department to collect SS data. CONCLUSION: Schools are collecting SS indicators at a relatively high rate, yet less than half of the data is reported to public health officials. Findings from this study indicate that public health officials can increase access to school-based SS data by approaching schools about collecting and reporting this important data. PMID- 26830344 TI - Interaction network of tobacco etch potyvirus NIa protein with the host proteome during infection. AB - BACKGROUND: The genomes of plant viruses have limited coding capacity, and to complete their infectious cycles, viral factors must target, direct or indirectly, many host elements. However, the interaction networks between viruses and host factors are poorly understood. The genus Potyvirus is the largest group of plus-strand RNA viruses infecting plants. Potyviral nuclear inclusion a (NIa) plays many roles during infection. NIa is a polyprotein consisting of two domains, viral protein genome-linked (VPg) and protease (NIaPro), separated by an inefficiently utilized self-proteolytic site. To gain insights about the interaction between potyviral NIa and the host cell during infection, we constructed Tobacco etch virus (TEV, genus Potyvirus) infectious clones in which the VPg or the NIaPro domains of NIa were tagged with the affinity polypeptide Twin-Strep-tag and identified the host proteins targeted by the viral proteins by affinity purification followed by mass spectrometry analysis (AP-MS). RESULTS: We identified 232 different Arabidopsis thaliana proteins forming part of complexes in which TEV NIa products were also involved. VPg and NIaPro specifically targeted 89 and 76 of these proteins, respectively, whereas 67 proteins were targeted by both domains and considered full-length NIa targets. Taking advantage of the currently known A. thaliana interactome, we constructed a protein interaction network between TEV NIa domains and 516 host proteins. The most connected elements specifically targeted by VPg were G-box regulating factor 6 and mitochondrial ATP synthase delta subunit; those specifically targeted by NIaPro were plasma membrane aquaporin PIP2;7 and actin 7, whereas those targeted by full-length NIa were heat shock protein 70-1 and photosystem protein LHCA3. Moreover, a contextualization in the global A. thaliana interactome showed that NIa targets are not more connected with other host proteins than expected by chance, but are in a position that allows them to connect with other host proteins in shorter paths. Further analysis of NIa-targeted host proteins revealed that they are mainly involved in response to stress, metabolism, photosynthesis, and localization. Many of these proteins are connected with the phytohormone ethylene. CONCLUSIONS: Potyviral NIa targets many host elements during infection, establishing a network in which information is efficiently transmitted. PMID- 26830345 TI - Hydrodynamic loading in concomitance with exogenous cytokine stimulation modulates differentiation of bovine mesenchymal stem cells towards osteochondral lineages. AB - BACKGROUND: Mesenchymal stem cells (MSCs) are viewed as a having significant potential for tissue engineering and regenerative medicine therapies. Clinical implementation of MSCs, however, demands that their preparation be stable and reproducible. Given that environmental and bioprocessing parameters such as substrate stiffness, seeding densities, culture medium composition, and mechanical loading can result in undirected differentiation of the MSC population, the objective of this study was to systematically investigate how hydrodynamic loading influences the differentiation of bone marrow-derived mesenchymal stem cells (MSCs) towards the osteochondral lineages both in the presence and absence of exogenous, inductive factors. METHODS: Expanded bovine MSCs were suspended in 2.5 % agarose, cast in a custom mold, and placed into either static or one of two dynamic culture environments consisting of "high" and "low" magnitude shear conditions. Constructs were supplemented with varying concentrations (0, 1, 10, 100 ng/mL) of either TGF-beta3 or BMP-2 throughout cultivation with tissue samples being collected following each week of culture. RESULTS: In the absence of exogenous supplementation, hydrodynamic loading had little effect on cell phenotype at either magnitude of stimulation. When cultures were supplemented with BMP-2 and TGF-beta3, MSCs gene expression progressed towards the osteogenic and chondrogenic pathways, respectively. This progression was enhanced by the presence of hydrodynamic loading, particularly under high shear conditions, but may point the chondrogenic cultures down a hypertrophic path toward osteogenesis reminiscent of endochondral ossification if TGF-beta3 supplementation is insufficient. CONCLUSIONS: Moving forward, these results suggest bioprocessing conditions which minimize exposure of chondrogenic cultures to fluid shear stress to avoid undesirable differentiation of the MSC population. PMID- 26830346 TI - Compensatory Actions of Ldb Adaptor Proteins During Corticospinal Motor Neuron Differentiation. AB - Although many genes that specify neocortical projection neuron subtypes have been identified, the downstream effectors that control differentiation of those subtypes remain largely unknown. Here, we demonstrate that the LIM domain-binding proteins Ldb1 and Ldb2 exhibit dynamic and inversely correlated expression patterns during cerebral cortical development. Ldb1-deficient brains display severe defects in proliferation and changes in regionalization, phenotypes resembling those of Lhx mutants. Ldb2-deficient brains, on the other hand, exhibit striking phenotypes affecting layer 5 pyramidal neurons: Immature neurons have an impaired capacity to segregate into mature callosal and subcerebral projection neurons. The analysis of Ldb2 single-mutant mice reveals a compensatory role of Ldb1 for Ldb2 during corticospinal motor neuron (CSMN) differentiation. Animals lacking both Ldb1 and Ldb2 uncover the requirement for Ldb2 during CSMN differentiation, manifested as incomplete CSMN differentiation, and ultimately leading to a failure of the corticospinal tract. PMID- 26830348 TI - Poor Oral Health and Diet in Relation to Weight Loss, Stable Underweight, and Obesity in Community-Dwelling Older Adults: A Cross-Sectional Study From the JAGES 2010 Project. AB - BACKGROUND: Involuntary weight loss and underweight increase the risks of mortality and disability in older people. However, the association and interaction of poor oral health and dietary intake with body mass index (BMI) have not been elucidated. METHODS: Data were analyzed for 96 794 respondents aged >65 years who were randomly selected from 31 Japanese municipalities in the Japan Gerontological Evaluation Study. Weight loss was defined as >=2-3 kg of loss over the preceding 6 months. BMI was evaluated in respondents without weight loss. Multiple logistic regression analysis was performed with weight loss, underweight, and obesity as dependent variables and having fewer teeth (<20) and infrequent food intake as independent variables, with adjustment for potential confounders. RESULTS: Weight loss was associated with having fewer teeth (men: odds ratio [OR] 1.3; 95% confidence interval [CI], 1.2-1.3; women: OR 1.2; 95% CI, 1.1-1.3) and infrequent fruit/vegetable intake (men: OR 1.1; 95% CI, 1.1-1.2; women: OR 1.4; 95% CI, 1.3-1.5) and fish/meat intake (OR 1.2; 95% CI, 1.1-1.3 for both sexes). No interaction was observed between having fewer teeth and food intake. Obesity was associated with the same factors: having fewer teeth (ORs 1.2 and 1.3 for men and women, respectively) and infrequent intake of fruit/vegetables (ORs 1.1 and 1.2 for men and women, respectively) and fish/meat (OR 1.1 for both sexes). Infrequent fruit/vegetable intake showed a higher OR for underweight in women with fewer teeth than for others. CONCLUSIONS: Having fewer teeth and infrequent food intake were associated with both weight loss and obesity. A significant interaction was observed in the associations of having fewer teeth and infrequent food intake with underweight in women. PMID- 26830347 TI - Effects of the BDNF Val66Met Polymorphism on Gray Matter Volume in Typically Developing Children and Adolescents. AB - The Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) is associated with psychiatric disorders and regional gray matter volume (rGMV) in adults. However, the relationship between BDNF and rGMV in children has not been clarified. In this 3-year cross-sectional/longitudinal (2 time points) study, we investigated the effects of BDNF genotypes on rGMV in 185 healthy Japanese children aged 5.7-18.4 using magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) analyses. We found that the volume of the right cuneus in Met homozygotes (Met/Met) was greater than in Val homozygotes (Val/Val) in both exams, and the left insula and left ventromedial prefrontal cortex volumes were greater in Val homozygotes versus Met homozygotes in Exam l. In addition, Met homozygous subjects exhibited higher processing speed in intelligence indices than Val homozygotes and Val/Met heterozygotes at both time points. Longitudinal analysis showed that the left temporoparietal junction volume of Val/Met heterozygotes increased more substantially over the 3-year study period than in Val homozygotes, and age-related changes were observed for the Val/Met genotype. Our findings suggest that the presence of 2 Met alleles may have a positive effect on rGMV at the developmental stages analyzed in this study. PMID- 26830349 TI - Higher Body Mass Index and Increased Prevalence of Paranasal Sinus Disease. AB - BACKGROUND: We hypothesized that higher body mass index (BMI) was associated with increased prevalence of paranasal sinus disease and examined the hypothesis in Japanese adults. METHODS: This was a cross-sectional study including 1350 Japanese adults aged 40 years or more who participated in a health check-up program focusing on brain diseases and metabolic syndrome. Participants were divided into quartiles of BMI levels. Paranasal sinus disease was confirmed by a head MRI scan. The association between BMI and paranasal sinus disease was examined using logistic regression analysis, which was adjusted for age, sex, waist:hip ratio, hemoglobin A1c, systolic blood pressure, smoking status, alcohol intake, and white blood cell count. RESULTS: Of the 1350 participants, 151 (11.2%) had paranasal sinus disease. In relation to those in the lowest quartile of BMI, the odds ratios of having the disease among those in the 2nd, 3rd, and 4th quartiles of BMI were 1.89 (95% confidence interval [CI], 1.03-3.48), 2.26 (95% CI, 1.20-4.23) and 2.26 (95% CI, 1.14-4.51), respectively. When BMI was analysed as a continuous variable, an increase of one unit in BMI was significantly associated with increased odds of having the disease, with an OR of 1.08 (95% CI, 1.01-1.16). CONCLUSIONS: The present study suggests that patients with higher BMI are more likely to have paranasal sinus disease. PMID- 26830350 TI - Investigation of the Relationship Between Chronic Stress and Insulin Resistance in a Chinese Population. AB - BACKGROUND: Chronic stress may facilitate the development of metabolic diseases. Insulin resistance is present long before the clinical manifestations of individual metabolic abnormalities. To explore whether chronic stress is an independent risk factor of insulin resistance, we investigated the relationship between the stress system, selected parameters of energy homeostasis, and insulin resistance in a Chinese population. METHODS: We recruited 766 workers employed at four companies in Beijing. The degree of insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). The highest quartile of HOMA-IR among all study subjects was further defined as insulin resistance in our study. The short standard version of the Copenhagen Psychosocial Questionnaire (COPSOQ) was used to assess job-related psychosocial stress. Pearson's correlation coefficients were calculated between cortisol level and HOMA-IR and components of metabolic syndrome, with stratification by gender. The relationship between cortisol and HOMA-IR independent of obesity was analyzed using a linear mixed model with company as a cluster unit. RESULTS: The values of the two scales of COPSOQ, including "demands at work" and "insecurity at work", were significantly associated with insulin resistance and cortisol concentration (P < 0.05). Cortisol was significantly positively correlated with glucose, HOMA IR, and waist circumference in males and females (P < 0.05). After adjusting for potential confounders, cortisol was an independent positive predictor for HOMA-IR (P < 0.05). CONCLUSIONS: These findings showed that chronic stress was associated with insulin resistance and may contribute to the development of insulin resistance. PMID- 26830351 TI - Prognostic Value of HIV-1 RNA on CD4 Trajectories and Disease Progression Among Antiretroviral-Naive HIV-Infected Adults in Botswana: A Joint Modeling Analysis. AB - Although HIV-1 RNA levels are measured at the time of initial diagnosis, the results are not used for the clinical follow-up of the patients. This study evaluates the prognostic value of the baseline HIV-1 RNA levels (above or below 10,000 copies/ml) on rate of disease progression, among antiretroviral therapy (ART)-naive patients in Botswana. A prospective cohort of 436 HIV-infected ART naive adults with baseline CD4 > 400 cells/mm(3) were followed quarterly for 5 years in an urban clinic in Botswana. Baseline HIV-1 RNA levels and longitudinal CD4(+) T-cell count data were analyzed, using mixed-effects regression jointly modeled with the times to a composite endpoint defined by AIDS-defining clinical conditions or death. During 1,547 person-years (PYs) follow-up time, 106 individuals became eligible for ART initiation (incidence rate: 0.07 PYs) and 6 participants died of AIDS-related illness. There were 203 (47%) individuals with baseline HIV-1 RNA <10,000 copies/ml and 233 (53%) individuals with baseline RNA >10,000 copies/ml. The slope of the predicted CD4 trajectory for individuals with baseline HIV-1 RNA >10,000 copies/ml is 30% steeper than that for those with baseline RNA <10,000. The hazard of reaching the composite endpoint for the individuals with baseline HIV-1 RNA >10,000 copies/ml was 2.3 (95% confidence interval: 1.5-3.0) times higher than that for those with baseline HIV-1 RNA <10,000 copies/ml. CD4 decline in individuals with HIV-1 RNA >10,000 copies/ml is much faster than that in those with RNA <10,000. The elevated HIV-1 RNA can be used as a marker to identify individuals at risk of faster disease progression. PMID- 26830352 TI - Warfarin related nephropathy: a case report and review of the literature. AB - BACKGROUND: Warfarin related nephropathy is one of the potential complications of warfarin therapy. Despite the well described histological entity, the clinical course and approach to warfarin related nephropathy in patients requiring life long anticoagulation is however not well described in the literature. CASE PRESENTATION: We report the clinical course of a 56 years old Chinese lady who presented with over anti-coagulation and acute kidney injury while on warfarin therapy for permanent atrial fibrillation and mechanical valve replacement. Renal biopsy was performed as the acute kidney injury was persistent despite normalization of the International Normalized Ratio and the diagnosis of warfarin related nephropathy was made. Temporary interruption of anti-coagulation, in combination with oral N-acetylcysteine resulted in subsequent stabilization of renal function. CONCLUSION: The diagnosis of warfarin induced nephropathy should be considered in patients presenting with unexplained acute kidney injury and over anti-coagulation. Awareness of this clinical entity is important for clinician managing anti-coagulation therapy and renal function should be monitored regularly in patients who are on warfarin therapy. PMID- 26830353 TI - Association between Prehospital CPR Quality and End-Tidal Carbon Dioxide Levels in Out-of-Hospital Cardiac Arrest. AB - INTRODUCTION: International Guidelines recommend measurement of end-tidal carbon dioxide (EtCO2) to enhance cardiopulmonary resuscitation (CPR) quality and optimize blood flow during CPR. Numerous factors impact EtCO2 (e.g., ventilation, metabolism, cardiac output), yet few clinical studies have correlated CPR quality and EtCO2 during actual out-of-hospital cardiac arrest (OHCA) resuscitations. The purpose of this study was to describe the association between EtCO2 and CPR quality variables during OHCA. METHODS: This is an observational study of prospectively collected CPR quality and capnography data from two EMS agencies participating in a statewide resuscitation quality improvement program. CPR quality and capnography data from adult (>=18 years) cardiac resuscitation attempts (10/2008-06/2013) were collected and analyzed on a minute-by-minute basis using RescueNetTM Code Review. Linear mixed effect models were used to evaluate the association between (log-transformed) EtCO2 level and CPR variables: chest compression (CC) depth, CC rate, CC release velocity (CCRV), ventilation rate. RESULTS: Among the 1217 adult OHCA cases of presumed cardiac etiology, 925 (76.0%) had a monitor-defibrillator file with CPR quality data, of which 296 (32.0%) cases had >1 minute of capnography data during CPR. After capnography quality review, 66 of these cases (22.3%) were excluded due to uninterpretable capnography, resulting in a final study sample of 230 subjects (mean age 68 years; 69.1% male), with a total of 1581 minutes of data. After adjustment for other CPR variables, a 10 mm increase in CC depth was associated with a 4.0% increase in EtCO2 (p < 0.0001), a 10 compression/minute increase in CC rate with a 1.7% increase in EtCO2 (p = 0.02), a 10 mm/second increase in CCRV with a 2.8% increase in EtCO2 (p = 0.03), and a 10 breath/minute increase in ventilation rate with a 17.4% decrease in EtCO2 (p < 0.0001). CONCLUSION: When controlling for known CPR quality variables, increases in CC depth, CC rate and CCRV were each associated with a statistically significant but clinically modest increase in EtCO2. Given the small effect sizes, the clinical utility of using EtCO2 to guide CPR performance is unclear. Further research is needed to determine the practicality and impact of using real-time EtCO2 to guide CPR delivery in the prehospital environment. PMID- 26830354 TI - Generation of Homogenous Three-Dimensional Pancreatic Cancer Cell Spheroids Using an Improved Hanging Drop Technique. AB - In vitro characterization of tumor cell biology or of potential anticancer drugs is usually performed using tumor cell lines cultured as a monolayer. However, it has been previously shown that three-dimensional (3D) organization of the tumor cells is important to provide insights on tumor biology and transport of therapeutics. Several methods to create 3D tumors in vitro have been proposed, with hanging drop technique being the most simple and, thus, most frequently used. However, in many cell lines this method has failed to form the desired 3D tumor structures. The aim of this study was to design and test an easy-to-use and highly reproducible modification of the hanging drop method for tumor sphere formation by adding methylcellulose polymer. Most pancreatic cancer cells do not form cohesive and manageable spheres when the original hanging drop method is used, thus we investigated these cell lines for our modified hanging drop method. The spheroids produced by this improved technique were analyzed by histology, light microscopy, immunohistochemistry, and scanning electron microscopy. Results show that using the proposed simple method; we were able to produce uniform spheroids for all five of the tested human pancreatic cancer cell lines; Panc-1, BxPC-3, Capan-1, MiaPaCa-2, and AsPC-1. We believe that this method can be used as a reliable and reproducible technique to make 3D cancer spheroids for use in tumor biology research and evaluation of therapeutic responses, and for the development of bio-artificial tissues. PMID- 26830356 TI - Host-parasite association in trombiculid mites (Actinotrichida: Trombiculidae) of temperate zone - the case of Hirsutiella zachvatkini (Schluger, 1948); are we dealing with prolonged contact with the host? AB - BACKGROUND: The time-extended contact of trombiculid larvae with hosts poses a question of its ecological determinants. The phenomenon, which may facilitate the overwintering of larvae in the temperate zone, was previously observed in few parasitengone taxa, but not confirmed for mammal-associated trombiculids. The study aims at tracing the phenology of larvae of Hirsutiella zachvatkini and at verifying the hypothesis of contact with the host, extending beyond the parasitic phase. METHODS: Apodemus agrarius, Apodemus flavicollis and Myodes glareolus, trapped during 2-year studies, were checked for the presence of trombiculid larvae. Larvae of H. zachvatkini served for the studies. The degree of mites' engorgement was checked over time in order to estimate the duration of feeding phase and to measure the maximum size increase. The experimental rearing aimed at ascertaining the relations between the level of engorgement and successful transformation of larva into subsequent instar. RESULTS: The mass appearance of larvae on hosts fell on autumn and winter, with a decrease observed in spring, leading to an almost total absence in early and mid summer. The highest intensity, attained in late autumn or in winter, was not followed by further increase in the number of host-associated larvae. The percentage of unengorged larvae on hosts was disproportionately small, irrespective of the season. The size increase of larva was 12.6-fold at maximum. Engorged or partly engorged larvae, observed from the beginning of mass appearance over the entire period of host-parasite association in the field, transformed into subsequent instar when removed from host. CONCLUSIONS: An increase in intensity observed from the onset of appearance of larvae on hosts, through autumn and winter months, at rarity of observations of unengorged larvae and absence of engorged larvae off-host, indicates a prolonged contact with hosts, aimed at synchronisation of life cycle, conditioned by food resources available for active postlarval forms and constitutes a strategy enabling larvae to survive the unfavourable winter conditions. The proportion of engorged and partly engorged vs. unfed larvae, observed over the survey, along with their ability to transform into subsequent instars, indicates a relatively short feeding phase. The lack of continuous increase in abundance and intensity towards spring and summer suggests a gradual detachment of partly and fully engorged larvae which attained the readiness to subsequent development. The size increase of larvae during their parasitic phase does not corroborate the neosomy in H. zachvatkini. Host-associated differences in topic preferences of the chiggers become less obvious at maximum infection rates. Quantitative descriptors of parasite population place M. glareolus among the most infected hosts of H. zachvatkini in contrast to Apodemus mice collected in the same habitat. PMID- 26830355 TI - Inositol 1,4,5-trisphosphate receptors and their protein partners as signalling hubs. AB - Inositol 1,4,5-trisphosphate receptors (IP3 Rs) are expressed in nearly all animal cells, where they mediate the release of Ca(2+) from intracellular stores. The complex spatial and temporal organization of the ensuing intracellular Ca(2+) signals allows selective regulation of diverse physiological responses. Interactions of IP3 Rs with other proteins contribute to the specificity and speed of Ca(2+) signalling pathways, and to their capacity to integrate information from other signalling pathways. In this review, we provide a comprehensive survey of the proteins proposed to interact with IP3 Rs and the functional effects that these interactions produce. Interacting proteins can determine the activity of IP3 Rs, facilitate their regulation by multiple signalling pathways and direct the Ca(2+) that they release to specific targets. We suggest that IP3 Rs function as signalling hubs through which diverse inputs are processed and then emerge as cytosolic Ca(2+) signals. PMID- 26830357 TI - Revealing new candidate genes for reproductive traits in pigs: combining Bayesian GWAS and functional pathways. AB - BACKGROUND: Reproductive traits such as number of stillborn piglets (SB) and number of teats (NT) have been evaluated in many genome-wide association studies (GWAS). Most of these GWAS were performed under the assumption that these traits were normally distributed. However, both SB and NT are discrete (e.g. count) variables. Therefore, it is necessary to test for better fit of other appropriate statistical models based on discrete distributions. In addition, although many GWAS have been performed, the biological meaning of the identified candidate genes, as well as their functional relationships still need to be better understood. Here, we performed and tested a Bayesian treatment of a GWAS model assuming a Poisson distribution for SB and NT in a commercial pig line. To explore the biological role of the genes that underlie SB and NT and identify the most likely candidate genes, we used the most significant single nucleotide polymorphisms (SNPs), to collect related genes and generated gene-transcription factor (TF) networks. RESULTS: Comparisons of the Poisson and Gaussian distributions showed that the Poisson model was appropriate for SB, while the Gaussian was appropriate for NT. The fitted GWAS models indicated 18 and 65 significant SNPs with one and nine quantitative trait locus (QTL) regions within which 18 and 57 related genes were identified for SB and NT, respectively. Based on the related TF, we selected the most representative TF for each trait and constructed a gene-TF network of gene-gene interactions and identified new candidate genes. CONCLUSIONS: Our comparative analyses showed that the Poisson model presented the best fit for SB. Thus, to increase the accuracy of GWAS, counting models should be considered for this kind of trait. We identified multiple candidate genes (e.g. PTP4A2, NPHP1, and CYP24A1 for SB and YLPM1, SYNDIG1L, TGFB3, and VRTN for NT) and TF (e.g. NF-kappaB and KLF4 for SB and SOX9 and ELF5 for NT), which were consistent with known newborn survival traits (e.g. congenital heart disease in fetuses and kidney diseases and diabetes in the mother) and mammary gland biology (e.g. mammary gland development and body length). PMID- 26830359 TI - High Throughput Screening for Colorectal Cancer Specific Compounds. AB - The development of new anti-cancer therapeutic agents is necessary to improve antitumor efficacy and reduce toxicities. Here we report using a systematic anticancer drug screening approach we developed previously, to concurrently screen colon and glioma cancer cell lines for 2000 compounds with known bioactivity and 1920 compounds with unknown activity. The hits specific to each tumor cell line were then selected, and further tested with the same cells transfected with EGFP (Enhanced Green Fluorescent Protein) alone. By comparing the percentage of signal reduction from the same cells transfected with the sensor-conjugated reporter system; hits preferably causing apoptosis were identified. Among the known lead compounds, many cardiac glycosides used as cardiotonic drugs were found to effectively and specifically kill colon cancer cells, while statins (hypolipidemic agents) used as cholesterol lowering drugs were relatively more effective in killing glioma cells. PMID- 26830358 TI - Probenecid and N-Acetylcysteine Prevent Loss of Intracellular Glutathione and Inhibit Neuronal Death after Mechanical Stretch Injury In Vitro. AB - Probenecid and N-acetylcysteine (NAC) can preserve intracellular levels of the vital antioxidant glutathione (GSH) via two distinct biochemical pathways. Probenecid inhibits transporter-mediated GSH efflux and NAC serves as a cysteine donor for GSH synthesis. We hypothesized that probenecid and NAC alone would maintain intracellular GSH concentrations and inhibit neuronal death after traumatic stretch injury, and that the drugs in combination would produce additive effects. Sex-segregated rat primary cortical neurons were treated with probenecid (100 MUM) and NAC (50 MUM), alone and in combination (Pro-NAC), then subjected to mechanical stretch (10s-1 strain rate, 50% membrane deformation). At 24 h, both probenecid and NAC inhibited trauma-induced intracellular GSH depletion, lactate dehydrogenase (LDH) release, and propidium iodide (PI) uptake in both XY- and XX-neurons. Combined Pro-NAC treatment was superior to probenecid or NAC alone in maintenance of intracellular GSH and neuronal death assessed by PI uptake. Interestingly, caspase 3 activity 24 h after mechanical trauma was more prominent in XX-neurons, and treatment effects (probenecid, NAC, and Pro NAC) were observed in XX- but not XY-neurons; however, XY-neurons were ultimately more vulnerable to mechanical stretch-induced injury than their XX counterparts, as was evidenced by more neuronal death detected by LDH release and PI uptake. In addition, after stretch injury in HT22 hippocampal cells, both NAC and probenecid were highly effective at reducing oxidative stress detected by dichlorofluorescein fluorescence. These in vitro data support further testing of this drug combination in models of traumatic neuronal injury in vivo. PMID- 26830360 TI - An Efficient Four-Step Approach Toward Fused Triazino[1,6-a] Quinazolines. AB - Herein, we describe a simple, four-step process for the preparation of 1,2,3 triazino[1,6- a]quinazolin-13-ones. This method involves ring-opening, quinazoline-forming condensation, reduction, diazotization accompanied by rapid intramolecular cyclization in the last step afforded the desired products with structurally complex heterocyclic core in excellent to high yields. PMID- 26830361 TI - Evaluation of the Aortic Arch from the Suprasternal Notch View Using Focused Cardiac Ultrasound. AB - BACKGROUND: The suprasternal notch view (SSNV) is an additional echocardiographic view not routinely used by emergency physicians (EPs) performing focused cardiac ultrasound (FOCUS). OBJECTIVE: This pilot study determined the ease and self perceived accuracy of the SSNV as performed by EPs. Additionally, we assessed the accuracy of FOCUS including the SSNV in thoracic aortic measurements compared to chest CT angiography (CTA). METHODS: This was a prospective, observational, pilot study of adult patients undergoing chest CTA. Thoracic aortic measurements were recorded at the sinus of Valsalva, sinotubular junction, and ascending aorta at its widest diameter in the parasternal long axis (PSL) view and SSNV. EPs rated ease of acquisition and self-perceived accuracy of thoracic aorta measurements. Two blinded radiologists performed thoracic aortic CTA measurements at predefined locations corresponding to the ultrasound measurements. RESULTS: Of the 79 patients (median age 57 years) enrolled, the SSNV was obtained in 97% of cases. EPs rated the ease of obtaining the SSNV as "easy" in 64.5% of cases and "very difficult" in 7.6% of cases. The mean difference between ultrasound (FOCUS plus SSNV) and CTA measurements were 1.2 mm (95% limits of agreement -2.9 to 5.3) at the sinus of Valsalva, 1.0 mm (95% limits of agreement -5.5 to 3.6 mm) at the sinotubular junction, 0.8 mm (95% limits of agreement -6.2 to 4.6 mm) at the proximal ascending aorta, and 0.6 mm (95% limits of agreement -2.8 to 4.0) at the aortic arch. CONCLUSIONS: Our findings suggest that the SSNV is an easily attainable and accurate view of the thoracic aorta that can be obtained by EPs in the majority of ED patients. PMID- 26830362 TI - Drowning in a Sea of Paperwork: Toward a More Patient-Centered Billing System in the United States. PMID- 26830363 TI - Progress in increasing affordability of medicines for non-communicable diseases since the introduction of mandatory health insurance in the Republic of Moldova. AB - BACKGROUND: To assess progress in improving affordability of medicines since the introduction of mandatory health insurance in the Republic of Moldova. METHOD: Using data from national health insurance, we estimate affordability of partially reimbursed medicines for the treatment of non-communicable diseases, and analyse which factors contributed to changes in affordability. RESULTS: Affordability of subsidized medicines improved over time. In 2013, it took a median of 0.84 days of income for the lowest income quintile (ranging from 0 to 3.32 days) to purchase 1 month of treatment for cardiovascular conditions in comparison to 1.85 days in 2006. This improvement however was mainly driven by higher incomes rather than deeper coverage through the reimbursement list. CONCLUSION: If mandatory health insurance is to improve affordability of medicines for the Moldovan population, more funds need to be (re-)allocated to enable higher percentage coverage of essential medicines and efficiencies need to be generated within the health system. These should include a budget reallocation between secondary and primary care, strengthening primary care to manage chronic conditions and raise population awareness, implementation of evidence-based selection and quality use of medicines in both outpatient and inpatient settings, improving monitoring and regulation of prices and the supply chain; and alignment of national treatment guidelines and clinical practice with international best practices and evidence based medicine. PMID- 26830364 TI - Workplace violence against nursing staff in a Saudi university hospital. AB - BACKGROUND: Violence against nurses is a major challenge for healthcare administrators. It is gaining more attention because it has a negative impact on nurses, the quality of health care and health organization. Common types of violence include physical harassment, sexual abuse, aggression, mobbing and bullying. Patients, their relatives and co-workers are considered the main perpetrators. AIM: To determine the prevalence rate of workplace violence against nursing professionals in a university hospital in Riyadh, Saudi Arabia, most frequent type and perpetrators as well as the contributing factors. METHODS: This quantitative cross-sectional study adapted a survey questionnaire from the Massachusetts Nurses Association Survey on Workplace Violence/Abuse to collect data from a quota sample of 370 nursing personnel. RESULTS: Almost half of the participants had experienced violence in the professional setting during the 12 months prior to the study. The majority of subjects perceived workplace violence as verbal abuse. Nearly all nursing professionals identified patients as the leading cause. Slightly more than half mentioned understaffing, misunderstandings, long waits for service and lack of staff training and policies for preventing crisis as contributing factors. CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: The prevalence rate is extremely high among nurses in the targeted Saudi university hospital. Saudi health as well as university hospitals' administration and policy makers should adopt and introduce a 'zero tolerance policy', set standards and develop practical measures for preventing the incidence and for controlling the prevalence of violence against nurses. Besides, healthcare organizations, particularly hospitals, can fulfil their obligations to provide both staff and patients with more secure environment. Further research on the topic is needed. PMID- 26830365 TI - An outbreak of norovirus infection associated with fermented oyster consumption in South Korea, 2013. AB - An acute gastroenteritis (AGE) outbreak was reported in May 2013 in Gyeonggi Province, South Korea. Eight students who had eaten breakfast on 21 May 2013 at a high-school restaurant exhibited AGE symptoms. Our case-control study showed that a strong association was observed between AGE symptoms and fermented oyster consumption. Virological studies also indicated that noroviruses (NoVs) were detected from both clinical samples and fermented oyster samples, and multiple different genotypes (genogroups GII.4, GII.11 and GII.14) of NoVs were present in both samples. The nucleotide sequence similarity between the strains found in the clinical samples and those in the fermented oysters was more than 99.5%. Therefore, to prevent further outbreaks, proper management of raw oysters is necessary and the food industry should be aware of the risk of viral gastroenteritis posed by fermented oysters contaminated with NoVs. PMID- 26830366 TI - Association Between Serum Levels of Testosterone and Estradiol With Meibomian Gland Assessments in Postmenopausal Women. AB - PURPOSE: The aims of this analysis were to determine if there is an association between serum levels of testosterone and estradiol with meibomian gland (MG) morphology and lipid layer thickness. METHODS: The data used for this analysis were collected from postmenopausal women with and without dry eye disease. Meibography was used to assess MG dropout on the central two-thirds of the eyelid and biomicroscopy was used for assessing MG expressibility and meibum quality. Venous blood samples were drawn for serum hormone level analysis. The Kruskal Wallis test and Spearman correlations were used for statistical analysis. RESULTS: One hundred ninety-eight postmenopausal women with an average age of 61.2 (+/- 9.1) years were included in this analysis. Testosterone levels showed significant differences between MG dropout grades 1 and 4 (P = 0.002) and grades 2 and 4 (P = 0.01), whereas estradiol levels were different based on MG dropout (P = 0.53). No significant correlations were found between testosterone (r = 0.10, P = 0.17) or estradiol (r = 0.05, P = 0.45) and lipid layer thickness. CONCLUSIONS: Testosterone levels were increased with MG dropout, which was significant between the mild and severe dropout groups, whereas no significant differences were found with estradiol and any MG assessment. Although the literature suggests an association of serum hormone levels and pathogenesis of dry eye disease in postmenopausal women, analysis of active sex steroid precursors and local tissue hormone levels may prove more useful. PMID- 26830367 TI - The Role of Sphingosine-1-Phosphate in Adipogenesis of Graves' Orbitopathy. AB - PURPOSE: To investigate the action of sphingosine-1-phosphate (S1P) in adipocyte differentiation of orbital fibroblasts and determine its putative role in the pathogenesis of Graves' orbitopathy (GO). METHODS: Primary preadipocyte orbital fibroblast cultures were stimulated for adipogenesis. Real-time PCR was performed to evaluate the expression of S1P receptor mRNA. To evaluate the effect of S1P and S1P receptor blockers (W146 and FTY720) on adipocyte differentiation, cultures were exposed to each receptor blocker for the first 4 days of the differentiation period. Differentiated cells were stained with Oil Red O, and the production of peroxisome proliferator activator gamma (PPARgamma) and CCAAT enhancer-binding proteins (C/EBP) alpha and beta were determined by Western blot analysis. RESULTS: Sphingosine-1-phosphate receptor 1, 2, and 3 mRNA expression levels were significantly higher in GO tissue samples than non-GO. Sphingosine-1 phosphate receptor 1 through 5 mRNA expression was significantly increased during the 10 days of adipogenesis. Sphingosine-1-phosphate treatment increased the size and number of adipocytes, and increased the expression of adipogenic transcriptional regulators. Treatment with S1P1 receptor inhibitor (W146) for 4 days after induction of adipogenesis attenuated adipocyte differentiation. Sphingosine-1-phosphate receptor blocker also decreased reactive oxygen species (ROS) production in GO orbital fibroblasts and H2O2-stimulated HO-1 production in GO orbital fibroblasts. S1P1 receptor inhibitor reduced the number of adipocytes and suppressed the accumulation of lipid droplets induced by 10 MUM H2O2 or 2% cigarette smoke extract (CSE) treatment. CONCLUSIONS: Sphingosine-1-phosphate could play a role in orbital adipocyte differentiation of GO. Modulation of S1P actions may provide a therapeutic target for the treatment of GO. PMID- 26830368 TI - Interleukin-17A Induces IL-1beta Secretion From RPE Cells Via the NLRP3 Inflammasome. AB - PURPOSE: Inflammasome activation and IL-1beta production have been proposed to have an important role in age-related macular degeneration (AMD). Growing evidence is emerging for involvement of interleukin-17A (IL-17A) in AMD pathogenesis. We investigated the effects of IL-17A on the activation of inflammasome and production of IL-1beta in primary human RPE cells. METHODS: Primary human RPE cells were isolated and cultured for the following experiments. Expression patterns of IL-17 receptor A (IL-17RA), IL-17 receptor C (IL-17RC), and ACT1 were analyzed by RT-PCR, flow cytometry, and immunofluorescence. IL-17A was added to the cell cultures, and cytokine expression, signaling pathways, and inflammasome machinery were investigated using real-time RT-PCR, ELISA, Western blot, flow cytometry, and small interfering RNA. RESULTS: Retinal pigment epithelial cells constitutively expressed IL-17RA, IL-17RC, and ACT1. IL-17A upregulated the mRNA levels of pro-IL-1beta, IL-8, CCL2, and CCL20, as well as the protein level of IL-1beta. IL-17A induced the phosphorylation of Akt, Erk1/2, p38 MAPK, and NF-kappaB p65 in RPE cells. Blocking NF-kappaB attenuated IL-17A induced expression of pro-IL-1beta mRNA. IL-17A enhanced pro-caspase-1 and NLRP3 mRNA expression. Inhibiting caspase-1 activity and silencing NLRP3 decreased IL 1beta secretion, confirming NLRP3 as the IL-17A-responsive inflammasome on the posttranscriptional level. The mechanism of IL-17A-triggered NLRP3 activation and subsequent IL-1beta secretion was found to involve the generation of reactive oxygen species. CONCLUSIONS: Our results suggest that IL-17A triggers a key inflammatory mediator, IL-1beta, from RPE cells, via NLRP3 inflammasome activation, holding therapeutic potential for AMD. PMID- 26830369 TI - Palisade Endings Are a Constant Feature in the Extraocular Muscles of Frontal Eyed, But Not Lateral-Eyed, Animals. AB - PURPOSE: To test whether palisade endings are a general feature of mammalian extraocular muscles (EOMs). METHODS: Thirteen species, some frontal-eyed (human, monkey, cat, and ferret), and others lateral-eyed (pig, sheep, calf, horse, rabbit, rat, mouse, gerbil, and guinea pig) were analyzed. Palisade endings were labeled by using different combinations of immunofluorescence techniques. Three dimensional reconstructions of immunolabeled palisade endings were done. RESULTS: In all frontal-eyed species, palisade endings were a consistent feature in the rectus EOMs. Their total number was high and they exhibited an EOM-specific distribution. In particular, the number of palisade endings in the medial recti was significantly higher than in the other rectus muscles. In the lateral-eyed animals, palisade endings were infrequent and, when present, their total number was rather low. They were only found in ungulates (sheep, calf, pig, and horse) and in rabbit. In rodents (rat, guinea pig, mouse, and gerbil) palisade endings were found infrequently (e.g., rat) or were completely absent. Palisade endings in frontal-eyed species and in some lateral-eyed species (pig, sheep, calf, and horse) had a uniform morphology. They generally lacked alpha-bungarotoxin staining, with a few exceptions in primates. Palisade endings in other lateral eyed species (rabbit and rat) exhibited a simplified morphology and bound alpha bungarotoxin. CONCLUSIONS: Palisade endings are not a universal feature of mammalian EOMs. So, if they are proprioceptors, not all species require them. Because in frontal-eyed species, the medial rectus muscle has the highest number of palisade endings, they likely play a special role in convergence. PMID- 26830370 TI - Structure/Psychophysical Relationships in X-Linked Retinoschisis. AB - PURPOSE: To compare structural properties from spectral-domain optical coherence tomography (SDOCT) and psychophysical measures from a subset of patients enrolled in a larger multicenter natural history study of X-linked retinoschisis (XLRS). METHODS: A subset of males (n = 24) participating in a larger natural history study of XLRS underwent high-resolution SDOCT. Total retina (TR) thickness and outer segment (OS) thickness were measured manually. Shape discrimination hyperacuity (SDH) and contour integration perimetry (CIP) were performed on an iPad with the myVisionTrack application. Sensitivity was measured with fundus guided perimetry (4-2 threshold testing strategy; 10-2 grid, spot size 3, 68 points). Correlation was determined with Pearson's r correlation. Values are presented as the mean +/- SD. RESULTS: Mean macular OS thickness was less in XLRS patients (17.2 +/- 8.1 MUm) than in controls (37.1 +/- 5.7 MUm; P < 0.0001) but mean TR thickness was comparable (P = 0.5884). For patients, total sensitivity was lower (13.2 +/- 6.6 dB) than for controls (24.2 +/- 2.4 dB; P = 0.0008) and had a strong correlation with photoreceptor OS (R(2) = 0.55, P = 0.0001) and a weak correlation with TR thickness (R(2) = 0.22, P = 0.0158). The XLRS subjects had a logMAR best corrected visual acuity (BCVA) of 0.5 +/- 0.3 that was associated with OS (R(2) = 0.79, P < 0.0001) but not TR thickness (R(2) = 0.01, P = 0.6166). Shape DH and CIP inner ring correlated with OS (R(2) = 0.33, P = 0.0085 and R(2) = 0.47, P = 0.0001, respectively) but not TR thickness (R(2) = 0.0004, P = 0.93; R(2) = 0.0043, P = 0.75, respectively). CONCLUSIONS: When considered from a single visit, OS thickness within the macula is more closely associated with macular function than TR thickness within the macula in patients with XLRS. PMID- 26830371 TI - The phagocytic fitness of leucopatches may impact the healing of chronic wounds. AB - Chronic non-healing wounds are significantly bothersome to patients and can result in severe complications. In addition, they are increasing in numbers, and a challenging problem to the health-care system. Handling of chronic, non-healing wounds can be discouraging due to lack of improvement, and a recent explanation can be the involvement of biofilm infections in the pathogenesis of non-healing wounds. Therefore, new treatment alternatives to improve outcome are continuously sought-after. Autologous leucopatches are such a new, adjunctive treatment option, showing promising clinical effects. However, the beneficial effect of the patches are not understood fully, although a major contribution is believed to be from the release of stimulating growth factors from activated thrombocytes within the leucopatch. Because the leucopatches also contain substantial numbers of leucocytes, the aim of the present study was to investigate the activity of the polymorphonuclear neutrophils (PMNs) within the leucopatch. By means of burst assay, phagocytosis assay, migration assay, biofilm killing assay and fluorescence in-situ hybridization (FISH) assay we showed significant respiratory burst in PMNs, active phagocytosis and killing of Pseudomonas aeruginosa by the leucopatch. In addition, bacterial-induced migration of PMNs from the leucopatch was shown, as well as uptake of P. aeruginosa by PMNs within the leucopatch. The present study substantiated that at least part of the beneficial clinical effect in chronic wounds by leucopatches is attributed to the activity of the PMNs in the leucopatch. PMID- 26830372 TI - Improving first-time donor attendance rates through the use of enhanced donor preparation materials. AB - BACKGROUND: Many nondonors are positive about blood donation and this motivates booking an appointment to donate. However, as their appointment approaches barriers to donating-such as anxiety-may become salient and deter attendance. Building on research of France and colleagues demonstrating the positive effect of enhanced preparation materials on donor recruitment, this study sought to determine whether these materials could effectively boost first donation appointment attendance. STUDY DESIGN AND METHODS: A field study comprising a 3 (brochure: none, e-mail, hard copy) * 2 (national call center [NCC] contact: none, call) between-subjects design was conducted with 3646 nondonors who had scheduled their first appointment. Participants in the brochure conditions received either a hard copy or an e-mailed link to electronic materials modeled on the donor preparation research of France and colleagues. Participants in the NCC call condition also received a call scripted in line with these preparation materials. The key outcome was new donor attendance rate. RESULTS: Although first appointment attendance rates were high in the control (no additional contact) condition at 85.07% of those not canceling in advance, dual exposure to the preparation materials through a NCC call and an electronic brochure boosted attendance. The relative risk of attending in the NCC call and electronic brochure condition was 1.0836 (95% confidence interval, 1.0352-1.1343; p = 0.0006), with attendance 8.36% higher than in the control. This gain in attendance came at a relative increase in recruitment costs of 2%. CONCLUSION: The use of tailored communication to address new donors' concerns and prepare them for donating bolsters attendance rates. PMID- 26830373 TI - Benign tracheal stenosis should never be stented with metallic devices. PMID- 26830374 TI - B-site ordered double perovskite LaBa1-xSrxZnSbO6 (0 <= x <= 1): Sr(2+)-doping induced symmetry evolution and structure-luminescence correlations. AB - The study of perovskites has been active for a long time. Here, we rationally designed and prepared a double perovskite, LaBaZnSbO6, by selecting Zn(2+) and Sb(5+) with large size and charge differences, and, indeed, complete B-site ordering can be achieved. Careful study using powder X-ray diffraction data pinpointed its space group to be I2/m, which has rarely been seen in double perovskites. Thereafter, an interesting observation of Sr(2+)-doping-induced symmetry evolution from I2/m to P21/n was confirmed in the complete solid solutions LaBa1-xSrxZnSbO6, where the tilting system also transferred from a(-)a( )c(0) to a(-)a(-)c(+). The transition boundary is around x = 0.4. It can also be visualized by the variation of theta (defined as c/[(a + b)/2]), which is associated with the anisotropic shrinkage of the unit cell lattice and indeed shows a minimum at x = 0.4. Such a successive modulation of both the structural symmetry and the average La/Ba/Sr-O bond distances (revealed by Rietveld refinements) motivated us to study the Eu(3+) luminescence in La0.95Eu0.05Ba1 xSrxZnSbO6. Interestingly, the maximum of charge transfer absorption of Eu(3+) shows a precise changing tendency with the A-O bond distances along with the Sr(2+) doping, clearly revealing the structure-luminescence correlations. PMID- 26830375 TI - Nanoscale zerovalent iron (nZVI) at environmentally relevant concentrations induced multigenerational reproductive toxicity in Caenorhabditis elegans. AB - Nanoscale zerovalent iron (nZVI) is widely used with large scale for environmental remediation for in situ or ex situ applications. The potential impact of nZVI on biota at environmentally relevant concentrations needs to be elucidated. In this study, the reproductive toxicities of three irons species: carboxymethyl cellulose (CMC)-stabilized nZVI, nanoscale iron oxide (nFe3O4), and ferrous ion (Fe(II)aq) in the soil-dwelling nematode Caenorhabditis elegans were examined. In addition, the generational transfer of reproductive toxicity of CMC nZVI on C. elegans was investigated. The results showed that CMC-nZVI, nFe3O4, and Fe(II)aq did not cause significant mortality after 24 h exposure at the examined concentrations. Reproductive toxicity assays revealed that CMC-nZVI, nFe3O4, and Fe(II)aq significantly decreased offsprings in parental generation (F0) in accompany with the increased intracellular reactive oxygen species (ROS). Furthermore, the reproductive toxicity of CMC-nZVI at environmentally relevant concentrations was transferrable from the F0 to the F1 and F2 generations, but then recovered in the F3 and F4 generations. Further evidence showed that total irons were accumulated in the F0 and F1 generations of C. elegans after CMC-nZVI parental exposure. This study demonstrated that environmentally relevant concentrations of CMC-nZVI induced multigenerational reproductive toxicity which can be ascribed to its high production of ROS in F0 generation, toxicity of Fe(II)aq, and iron accumulation in C. elegans. Since nZVI is widely used for environmental remediation, considering the multigenerational toxicity, this study thus implicates a potential environmental risk of nZVI-induced nanotoxicity in the environment. PMID- 26830376 TI - Proton therapy for paediatric medulloblastoma. PMID- 26830378 TI - Computer-aided diagnosis of psoriasis skin images with HOS, texture and color features: A first comparative study of its kind. AB - Psoriasis is an autoimmune skin disease with red and scaly plaques on skin and affecting about 125 million people worldwide. Currently, dermatologist use visual and haptic methods for diagnosis the disease severity. This does not help them in stratification and risk assessment of the lesion stage and grade. Further, current methods add complexity during monitoring and follow-up phase. The current diagnostic tools lead to subjectivity in decision making and are unreliable and laborious. This paper presents a first comparative performance study of its kind using principal component analysis (PCA) based CADx system for psoriasis risk stratification and image classification utilizing: (i) 11 higher order spectra (HOS) features, (ii) 60 texture features, and (iii) 86 color feature sets and their seven combinations. Aggregate 540 image samples (270 healthy and 270 diseased) from 30 psoriasis patients of Indian ethnic origin are used in our database. Machine learning using PCA is used for dominant feature selection which is then fed to support vector machine classifier (SVM) to obtain optimized performance. Three different protocols are implemented using three kinds of feature sets. Reliability index of the CADx is computed. Among all feature combinations, the CADx system shows optimal performance of 100% accuracy, 100% sensitivity and specificity, when all three sets of feature are combined. Further, our experimental result with increasing data size shows that all feature combinations yield high reliability index throughout the PCA-cutoffs except color feature set and combination of color and texture feature sets. HOS features are powerful in psoriasis disease classification and stratification. Even though, independently, all three set of features HOS, texture, and color perform competitively, but when combined, the machine learning system performs the best. The system is fully automated, reliable and accurate. PMID- 26830377 TI - Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: a phase 2 single-arm study. AB - BACKGROUND: Compared with traditional photon radiotherapy, proton radiotherapy irradiates less normal tissue and might improve health outcomes associated with photon radiotherapy by reducing toxic effects to normal tissue. We did a trial to assess late complications, acute side-effects, and survival associated with proton radiotherapy in children with medulloblastoma. METHODS: In this non randomised, open-label, single-centre, phase 2 trial, we enrolled patients aged 3 21 years who had medulloblastoma. Patients had craniospinal irradiation of 18-36 Gy radiobiological equivalents (GyRBE) delivered at 1.8 GyRBE per fraction followed by a boost dose. The primary outcome was cumulative incidence of ototoxicity at 3 years, graded with the Pediatric Oncology Group ototoxicity scale (0-4), in the intention-to-treat population. Secondary outcomes were neuroendocrine toxic effects and neurocognitive toxic effects, assessed by intention-to-treat. This study is registered at ClinicalTrials.gov, number NCT00105560. FINDINGS: We enrolled 59 patients from May 20, 2003, to Dec 10, 2009: 39 with standard-risk disease, six with intermediate-risk disease, and 14 with high-risk disease. 59 patients received chemotherapy. Median follow-up of survivors was 7.0 years (IQR 5.2-8.6). All patients received the intended doses of proton radiotherapy. The median craniospinal irradiation dose was 23.4 GyRBE (IQR 23.4-27.0) and median boost dose was 54.0 GyRBE (IQR 54.0-54.0). Four (9%) of 45 evaluable patients had grade 3-4 ototoxicity according to Pediatric Oncology Group ototoxicity scale in both ears at follow-up, and three (7%) of 45 patients developed grade 3-4 ototoxicity in one ear, although one later reverted to grade 2. The cumulative incidence of grade 3-4 hearing loss at 3 years was 12% (95% CI 4-25). At 5 years, it was 16% (95% CI 6-29). Pediatric Oncology Group hearing ototoxicity score at a follow-up of 5.0 years (IQR 2.9-6.4) was the same as at baseline or improved by 1 point in 34 (35%) of 98 ears, worsened by 1 point in 21 (21%), worsened by 2 points in 35 (36%), worsened by 3 points in six (6%), and worsened by 4 points in two (2%). Full Scale Intelligence Quotient decreased by 1.5 points (95% CI 0.9-2.1) per year after median follow-up up of 5.2 years (IQR 2.6-6.4), driven by decrements in processing speed and verbal comprehension index. Perceptual reasoning index and working memory did not change significantly. Cumulative incidence of any neuroendocrine deficit at 5 years was 55% (95% CI 41-67), with growth hormone deficit being most common. We recorded no cardiac, pulmonary, or gastrointestinal late toxic effects. 3-year progression free survival was 83% (95% CI 71-90) for all patients. In post-hoc analyses, 5 year progression-free survival was 80% (95% CI 67-88) and 5-year overall survival was 83% (95% CI 70-90). INTERPRETATION: Proton radiotherapy resulted in acceptable toxicity and had similar survival outcomes to those noted with conventional radiotherapy, suggesting that the use of the treatment may be an alternative to photon-based treatments. FUNDING: US National Cancer Institute and Massachusetts General Hospital. PMID- 26830379 TI - Multilevel principal component analysis (mPCA) in shape analysis: A feasibility study in medical and dental imaging. AB - BACKGROUND AND OBJECTIVE: Methods used in image processing should reflect any multilevel structures inherent in the image dataset or they run the risk of functioning inadequately. We wish to test the feasibility of multilevel principal components analysis (PCA) to build active shape models (ASMs) for cases relevant to medical and dental imaging. METHODS: Multilevel PCA was used to carry out model fitting to sets of landmark points and it was compared to the results of "standard" (single-level) PCA. Proof of principle was tested by applying mPCA to model basic peri-oral expressions (happy, neutral, sad) approximated to the junction between the mouth/lips. Monte Carlo simulations were used to create this data which allowed exploration of practical implementation issues such as the number of landmark points, number of images, and number of groups (i.e., "expressions" for this example). To further test the robustness of the method, mPCA was subsequently applied to a dental imaging dataset utilising landmark points (placed by different clinicians) along the boundary of mandibular cortical bone in panoramic radiographs of the face. RESULTS: Changes of expression that varied between groups were modelled correctly at one level of the model and changes in lip width that varied within groups at another for the Monte Carlo dataset. Extreme cases in the test dataset were modelled adequately by mPCA but not by standard PCA. Similarly, variations in the shape of the cortical bone were modelled by one level of mPCA and variations between the experts at another for the panoramic radiographs dataset. Results for mPCA were found to be comparable to those of standard PCA for point-to-point errors via miss-one-out testing for this dataset. These errors reduce with increasing number of eigenvectors/values retained, as expected. CONCLUSIONS: We have shown that mPCA can be used in shape models for dental and medical image processing. mPCA was found to provide more control and flexibility when compared to standard "single-level" PCA. Specifically, mPCA is preferable to "standard" PCA when multiple levels occur naturally in the dataset. PMID- 26830381 TI - Laparoscopic single port pseudo-continent perineal colostomy. PMID- 26830380 TI - Twin Birth Study: 2-year neurodevelopmental follow-up of the randomized trial of planned cesarean or planned vaginal delivery for twin pregnancy. AB - BACKGROUND: The Twin Birth Study randomized women with uncomplicated pregnancies, between 32(0/7)-38(6/7) weeks' gestation where the first twin was in cephalic presentation, to a policy of either a planned cesarean or planned vaginal delivery. The primary analysis showed that planned cesarean delivery did not increase or decrease the risk of fetal/neonatal death or serious neonatal morbidity as compared with planned vaginal delivery. OBJECTIVE: This study presents the secondary outcome of death or neurodevelopmental delay at 2 years of age. STUDY DESIGN: A total of 4603 children from the initial cohort of 5565 fetuses/infants (83%) contributed to the outcome of death or neurodevelopmental delay. Surviving children were screened using the Ages and Stages Questionnaire with abnormal scores validated by a clinical neurodevelopmental assessment. The effect of planned cesarean vs planned vaginal delivery on death or neurodevelopmental delay was quantified using a logistic model to control for stratification variables and using generalized estimating equations to account for the nonindependence of twin births. RESULTS: Baseline maternal, pregnancy, and infant characteristics were similar. Mean age at assessment was 26 months. There was no significant difference in the outcome of death or neurodevelopmental delay: 5.99% in the planned cesarean vs 5.83% in the planned vaginal delivery group (odds ratio, 1.04; 95% confidence interval, 0.77-1.41; P = .79). CONCLUSION: A policy of planned cesarean delivery provides no benefit to children at 2 years of age compared with a policy of planned vaginal delivery in uncomplicated twin pregnancies between 32(0/7)-38(6/7)weeks' gestation where the first twin is in cephalic presentation. PMID- 26830382 TI - The role of lymphatics in portal biliopathy. PMID- 26830383 TI - A Journal of Visceral Surgery with international standing that enhances the recognition of authors, clearly states all links of interest and is plagiarism free--we owed you this much. PMID- 26830384 TI - Conservation of the left colic artery during laparoscopic left-hemicolectomy for cancer. PMID- 26830385 TI - Successful treatment of Juvenile parkinsonism with bilateral subthalamic deep brain stimulation in a 14-year-old patient with parkin gene mutation. PMID- 26830386 TI - [Role of the poultry red mite (Dermanyssus gallinae) in the transmission of avian influenza A virus]. AB - OBJECTIVE: The aim of this study was to investigate the role of the poultry red mite (Dermanyssus [D.] gallinae) in the horizontal transmission of avian influenza A virus (AIV) to chickens. This mite is the most common ectoparasite in poultry worldwide, and may play a role in the spread of infectious agents including AIV. Currently, the control of mites is difficult due to frequently developed resistance to many acaricides, their nocturnality and their ability to survive hidden without feeding for months. MATERIALS AND METHODS: D. gallinae were collected in a commercial layer farm and housed in self-made fibreboard boxes. SPF chickens were intravenously infected with AIV strain A/turkey/Ontario/7732/1966 (H5N9). The viraemia in chickens was monitored and at an appropriate time point about 1000 mites were allowed to suck on the AIV infected chickens. Re-isolation of the virus from blood-filled mites was tried daily for 14 days using chicken embryo fibroblast cultures and embryonated chicken eggs. Subsequently, the virus containing mites were placed into boxes that contained naive SPF chickens to enable virus transmission from mites to chickens. Possible transmission to the chickens was examined using clinical signs, serology, gross lesions, histopathology and immunohistochemistry. RESULTS: Chickens developed a dose-dependent viraemia one day after infection, therefore this day was chosen for the bloodmeal of the mites. AIV was detected in mites after bloodsucking on AIV-infected chickens over a 10-day period. Naive SPF chickens were infected during bloodsucking of AIV carrying mites. AIV isolates in mites and in chickens were undistinguishable from the original AIV inoculum by RT PCR. CONCLUSIONS: D. gallinae ingested AIV during bloodmeals on AIV infected chickens and are able to transmit AIV to SPF chickens. Therefore, mites serve as mechanical vector of AIV and may play a major role in the circulation of AIV within a facility or area although the life span of infectious virus in the mite is limited. CLINICAL RELEVANCE: The proven transmission requires more than ever a systematic control of this ectoparasite in order to maintain poultry health and productivity. The demonstrated vector function of this mite is of great significance for poultry flocks all over the world. PMID- 26830387 TI - Incidence and patterns of hemolytic anemia in acute dapsone overdose. AB - BACKGROUND: Hemolytic anemia is one of the complications related to the chronic consumption of dapsone. However, in acute dapsone overdose, there have been few case reports regarding hemolytic anemia. Herein, we reported the prevalence and patterns of hemolytic anemia in acute dapsone overdose, and compared clinical features including mortality in the non-hemolytic anemia and the hemolytic anemia groups. METHODS: We conducted a retrospective review of 43 consecutive acute dapsone overdose cases that were diagnosed and treated at the emergency department of the Wonju Severance Christian Hospital between January 2006 and January 2014. RESULTS: There were 13 male patients (30.2%) and the ages of all patients ranged from 18 to 93 years with a median of 67 years. The ingested dose varied from a minimum of two 100-mg tablet to a maximum of twenty five 100-mg tablets. All patients had methemoglobinemia irrespective of the presence of hemolytic anemia. Among 43 patients, 30 patients (69.8%) were shown to have hemolytic anemia and hemolytic anemia developed the day after admission and persisted for more than 6 days after admission. Even though mortality rate was not significantly higher in the hemolytic anemia group, the hemolytic anemia group had significantly longer total admission and intensive care unit admission stays than the non-hemolytic group. CONCLUSIONS: A significant proportion of the patients with acute dapsone overdose is associated with occurrence of hemolytic anemia. Hemolytic anemia may be developed the day after admission and persisted for more than 6 days after admission. Therefore, monitoring of serum hemoglobin level is necessary. PMID- 26830388 TI - May-Thurner syndrome as the cause of phlegmasia cerulea dolens. PMID- 26830389 TI - Advanced intravenous access: technique choices, pain scores, and failure rates in a local registry. AB - BACKGROUND: When an intravenous (IV) catheter is needed and the common approach of inspection and palpation fails, an advanced access technique becomes necessary. Our objectives were to estimate pain scores, operator times, success rates, and complication rates when advanced techniques are used in a clinical setting. METHODS: We enrolled patients who had a need for advanced IV access and were able to give informed consent to participate in our study. We collected data on operator type, technique, initial success, number of attempts, skin punctures, operator time, pain scores, and complications. We estimated confidence intervals for proportions using normal binomial approximation or exact calculation. RESULTS: The registry documented 154 attempts in 116 patients. The median time from triage to establishment of an IV line was 203 minutes; multiple advanced attempts were required in 24% of cases. Most attempts (95%) used either ultrasound-guided cannulation of a peripheral vein (PUG) (108) or cannulated the external jugular vein (EJ) (38). These 2 methods yielded similar pain scores (4.3 4.5), but PUG required more skin punctures (1.6 vs 1.2) and longer operator time (17.7 vs 11.9 minutes). The only complication was IV line failure, occurring in 6% (95% confidence interval, 0%-18%) of EJ approaches and 27% (95% confidence interval, 18%-38%) of the PUG scenarios. CONCLUSION: Most attempts to establish IV access used PUG or the EJ. External jugular vein cannulation was achieved more quickly, with fewer skin punctures and a lower rate of postinsertion failure, than PUG. PMID- 26830390 TI - Axillary artery laceration after an anterior shoulder dislocation presenting as hypovolemic shock. PMID- 26830391 TI - Achieving ventricular rate control using metoprolol in beta-blocker-naive patients vs patients on chronic beta-blocker therapy. AB - STUDY OBJECTIVE: The objective of the study is to evaluate the difference in ventricular rate control using an intravenous (IV) metoprolol regimen commonly used in clinical practice in patients receiving chronic beta-blocker therapy compared to patients considered beta-blocker naive admitted to the emergency department (ED) for atrial fibrillation (AF) with rapid ventricular rate. METHODS: A single-center retrospective cohort study of adult ED patients who were admitted with a rapid ventricular rate of 120 beats per minute (bpm) or greater and treated with IV metoprolol was performed. Rate control was defined as either a decrease in ventricular rate to less than 100 bpm or a 20% decrease in heart rate to less than 120 bpm after metoprolol administration. Patient demographics, differences in length of stay, and adverse events were recorded. RESULTS: A total of 398 patients were included in the study, with 79.4% (n=316) receiving chronic beta-blocker therapy. Patients considered to be beta-blocker naive were more likely to achieve successful rate control with IV metoprolol compared to patients on chronic beta-blocker therapy (56.1% vs 42.4%; P=.03). beta-Blocker-naive status was associated with a shorter length of stay in comparison to patients receiving chronic beta-blocker therapy (1.79 vs 2.64 days; P<.01). CONCLUSION: Intravenous metoprolol for the treatment of atrial fibrillation with rapid ventricular rate was associated with a higher treatment response in patients considered beta-blocker naive compared to patients receiving chronic beta-blocker therapy. PMID- 26830392 TI - Obesity, ultrasound indexes of fat depots and lipid goal attainment in patients with high and very high cardiovascular risk: A novel approach towards better risk reduction. AB - AIM: Our aim was to assess the attainment of primary (low density lipoprotein cholesterol; LDL-C) and secondary (non-high density lipoprotein cholesterol; non HDL-C) lipid therapeutic goals in relation to obesity, clinical measures of adiposity and ultrasound indexes of fat depots, including the novel index of periarterial adipose tissue (PAT): carotid artery extra media thickness (EMT). METHODS AND RESULTS: High and very high cardiovascular (CV) risk patients (n = 420; F/M: 34/66%; age: 61.2 +/- 7 years) with prior statin treatment (>= 18 months) were enrolled into this cross-sectional study. All patients had a detailed assessment with several anthropometric measures and ultrasound indexes of fat depots indexed to BMI: abdominal (Intra-abdominal Fat Thickness; IAT and Pre-peritoneal Fat Thickness; PreFT), paracardial (Epicardial Fat Thickness; EFT and Pericardial Fat Thickness; PFT) and the new index corresponding to PAT (carotid EMT). Lipid goals attainment in the study group was as follows: 34% (LDL C goal), 39% (non-HDL-C goal) and 35% (both LDL and non-HDL-C goals). Among ultrasound indexes, patients with both lipid goals attainment revealed significantly lower carotid EMT/BMI (LDL-C goal: 25.2 +/- 4.2 vs 27.5 +/- 4.1, p < 0.01 and non-HDL-C goal: 26.1 +/- 4 vs 27.7 +/- 4.2, p < 0.01) and IAT/BMI (LDL C goal: 2.35 +/- 0.66 vs 2.51 +/- 0.71, p = 0.02 and non-HDL-C goal: p = ns) compared to individuals without goals achievement. Moreover, lipid goals attainment was associated with both measures: carotid EMT/BMI (LDL-C goal: r = 0.2, p < 0.05 and non-HDL-C goal: r = -0.2, p < 0.05) and IAT/BMI (LDL-C goal: r = -0.2, p < 0.05 and non-HDL-C goal: r = -0.2, p < 0.05). Multivariable regression analysis showed also independent association between carotid EMT/BMI and both goals achievement: LDL-C (p = 0.01) and non-HDL-C goal (p = 0.01). Other fat depots indexes (EFT, PFT and PreFT) failed to provide additional data. CONCLUSION: Contrary to overall obesity and most clinical measures of adiposity, carotid EMT and abdominal IAT, but not other ultrasound indexes of fat depots revealed associations independent from BMI with lipid goal attainment and may help identify patients requiring more aggressive lipid management. PMID- 26830393 TI - Modeling the course and outcomes of multiple sclerosis is statistical twaddle- Yes. PMID- 26830394 TI - Modeling the course and outcomes of MS is statistical twaddle--No. PMID- 26830395 TI - Modeling the course and outcomes of MS is statistical twaddle--Commentary. PMID- 26830396 TI - Detection of Helicobacter pylori in Nasal Polyps. AB - To detect the presence of Helicobacter pylori in nasal polyps. A case-control study was conducted enrolling 35 patients with nasal polyps (cases) and patients undergoing septoplasty (controls). Fresh tissue samples were used for urea broth test and imprint cytology, while formalin fixed tissue sections were used for morphology, special stains and immunohistochemistry for H. pylori. Fresh stool samples from both groups were tested to correlate the gastrointestinal status. H. pylori was detected in 40.0 % (14/35) of cases and 8.5 % of controls (3/35) (p = 0.004) by immunohistochemistry. Amongst cases, eight were positive with urea broth test, six with imprint cytology (Giemsa stain), three with H & E, and nine with modified McMullen's stain. Hyperplasia of the lining epithelium and lymphoid aggregates were significantly noticed in nasal polyps positive for H. pylori. Stool antigen test was positive in subjects who were positive for H. pylori in the nasal mucosa. There appears to be an association between H. pylori and nasal polyps. Immunohistochemistry is more sensitive and specific method to detect H. pylori. H. pylori induced inflammatory tissue reaction pattern indicates a possible causal association. Further studies are needed to prove the causal relationship between H. pylori and nasal polyps. PMID- 26830397 TI - Hematolymphoid Lesions of the Sinonasal Tract. AB - Hematolymphoid neoplasms of the sinonasal tract are rare and the majority represents non-Hodgkin lymphomas. This review will focus on morphologic, immunophenotypic, and genetic characteristics of the most common types of non Hodgkin lymphoma, namely diffuse large B cell lymphoma and extranodal natural killer/T-cell lymphoma, nasal type, but also include the discussion of less frequent other hematolymphoid entities, such as extranodal plasmacytomas and Rosai-Dorfman disease. PMID- 26830398 TI - Update on Select Benign Mesenchymal and Meningothelial Sinonasal Tract Lesions. AB - Several benign and malignant mesenchymal and meningothelial lesions may preferentially affect or extend into the sinonasal tract. Glomangiopericytoma (GPC, formerly sinonasal-type hemangiopericytoma) is a specific tumor with a predilection to the sinonasal tract. Sinonasal tract polyps with stromal atypia (antrochoanal polyp) demonstrate unique histologic findings in the sinonasal tract. Juvenile nasopharyngeal angiofibroma (JNA) arises from specialized tissue in this location. Meningioma may develop as direct extension from its intracranial counterpart or as an ectopic tumor. Selected benign mesenchymal tumors may arise in the sinonasal tract and pose a unique differential diagnostic consideration, such as solitary fibrous tumor and GPC or lobular capillary hemangioma and JNA. Although benign and malignant vascular, fibrous, fatty, skeletal muscle, and nerve sheath tumors may occur in this location, this paper focuses on a highly select group of rare benign sinonasal tract tumors with their clinicopathological and molecular findings, and differential diagnosis. PMID- 26830399 TI - Sinonasal Adenocarcinoma: Update on Classification, Immunophenotype and Molecular Features. AB - Adenocarcinomas of the sinonasal tract may originate from respiratory surface epithelium or the underlying seromucinous glands. These malignancies are divided into salivary-type adenocarcinomas and non-salivary-type adenocarcinomas. The latter are further divided into intestinal-type and nonintestinal-type adenocarcinomas. This review provides an update on tumor classification, differential diagnostic considerations and molecular features, as well as new adenocarcinoma entities in the sinonasal area. PMID- 26830400 TI - Neuroendocrine Neoplasms of the Sinonasal Tract: Neuroendocrine Carcinomas and Olfactory Neuroblastoma. AB - Neuroendocrine neoplasms (NENs) can occur in organs or tissues that do not contain neuroendocrine cells normally and do not necessarily imply embryologic derivation from the neuroectoderm; but rather reflect a shared phenotype characterized by the expression of multiple genes encoding both endocrine and neuronal features. NENs are rare in the sinonasal tract and are subdivided into epithelial and neural subtypes based on the presence of keratins or neurofilaments, respectively. Although relatively rare, neuroendocrine carcinomas (NECs) and olfactory neuroblastoma (ONB) are the most common neuroendocrine neoplasms of the sinonasal tract. The focus of this review is to highlight recent developments in the pathology of sinonasal NECs and ONB in light of the upcoming update of the World Health Organization (WHO) 2005 classification of tumors of the head and neck. PMID- 26830401 TI - An Update on Sinonasal Round Cell Undifferentiated Tumors. AB - The sinonasal cavities host a wide variety of undifferentiated malignancies with round cell morphology, including neoplasms of epithelial, mesenchymal, neuroectodermal, and hematolymphoid lineage. The differential diagnosis may be difficult, especially in small biopsy material, due to overlapping morphology, but their correct classification is clinically relevant. The aim of this review is to provide practical guidelines for the differential diagnosis of these malignancies, with emphasis on recently described entities and special reference to the role of ancillary techniques. PMID- 26830402 TI - Sinonasal Squamous Cell Carcinoma: A Review with Emphasis on Emerging Histologic Subtypes and the Role of Human Papillomavirus. AB - The sinonasal tract is one of the least frequent sites for squamous cell carcinoma in the head and neck. However, it is still a complex tumor type for pathologists because there are numerous histologic variants with unusual morphologic features, several non-squamous carcinomas in the differential diagnosis that can have similar morphology and even squamous differentiation, and because of the increasing recognition of human papillomavirus (HPV) in a subset of the tumors. In addition, the unique and complex anatomy of the sinonasal tract can make proper staging and management of patients' tumors quite challenging. This article reviews sinonasal tract squamous cell carcinoma in depth and provides the latest data on Schneiderian papillomas and HPV in their pathogenesis. PMID- 26830403 TI - Low-Grade Epithelial Proliferations of the Sinonasal Tract. AB - Low-grade epithelial proliferations of the sinonasal tract include Schneiderian papillomas, respiratory epithelial adenomatoid hamartoma, seromucinous hamartoma and low-grade non-intestinal adenocarcinoma. There is considerable overlap in their clinical presentation, endoscopic appearance, and imaging features. Although well-described diagnostic criteria exist, a definitive diagnosis may be difficult to reach on a small biopsy. Schneiderian papillomas are divided into fungiform, inverted, and oncocytic types, each with characteristic clinical and morphological features. The latter two may progress to malignancy. The majority are still considered to be HPV-related. Two lesions are designated as hamartomas, but their pathogenesis remains uncertain, with inflammatory and neoplastic origins proposed. Respiratory epithelial adenomatoid hamartoma is increasingly being recognized for its association with chronic rhinosinusitis and olfactory cleft site of origin. Seromucinous hamartoma has gained attention in recent years and overlaps with both respiratory epithelial adenomatoid hamartoma and low-grade non-intestinal adenocarcinoma. Controversy surrounds their distinction, particularly from low-grade adenocarcinoma. The latter generally is cured by complete excision, with a 26 % risk of recurrence but rare metastases and deaths from disease. PMID- 26830404 TI - Pathology of Fungal Rhinosinusitis: A Review. AB - Fungal rhinosinusitis (FRS) comprises a spectrum of disease processes that vary in clinical presentation, histologic appearances, and biological significance. FRS can be acute or chronic and is most commonly classified as non-invasive or invasive based on whether fungi have invaded into tissue. This manuscript will review the pathologic classification of FRS. PMID- 26830405 TI - Non-infectious Inflammatory Lesions of the Sinonasal Tract. AB - This review covers the histopathology and pathogenesis of non-infectious inflammatory diseases of the sinonasal tract, in particular, sarcoidosis, granulomatous vasculitides Wegener, Churg-Strauss), relapsing polychondritis, eosinophilic angiocentric fibrosis, chronic rhinosinusitis and nasal perforations. Molecular associations and mechanisms are emphasised to assist pathologists to put their observations into the context of clinical, genetic and environmental influences on patients' diseases. PMID- 26830406 TI - Newly Described Tumor Entities in Sinonasal Tract Pathology. AB - Surgical pathology of the sinonasal tract (nasal cavity and paranasal sinuses) is extremely challenging due in part to the tremendous diversity of tumor types that may arise in this region. Compounding the difficulty, a number of new sinonasal tumor entities have been recently described, and pathologists may not yet be familiar with these neoplasms. This manuscript will review the clinicopathologic features of some of the newly described sinonasal tumor types: NUT midline carcinoma, HPV-related carcinoma with adenoid cystic-like features, SMARCB1 (INI 1) deficient sinonasal carcinoma, biphenotypic sinonasal sarcoma, and renal cell like adenocarcinoma. PMID- 26830407 TI - Endonasal Endoscopic Surgery in the Management of Sinonasal and Anterior Skull Base Malignancies. AB - Sinonasal malignancies represent a rare subset of tumors with a wide variety of histopathologic diagnoses and overall poor prognosis. These tumors tend to have an insidious onset with non-specific symptoms which often leads to delayed diagnosis and advanced local disease at presentation. The principal goal of surgery is to obtain a negative margin resection. Open craniofacial techniques are well established in the management of sinonasal malignancies and remain the treatment of choice for many advanced tumors. Over the past couple of decades, there has been tremendous application of endoscopic techniques to skull base pathologies including sinonasal malignancies. For selected cases, endonasal endoscopic techniques can be performed with curative intent and reduced surgical morbidity and mortality. Here we discuss principles of surgical management of sinonasal malignancies, review the techniques of endonasal endoscopic resection of sinonasal malignancies, and highlight the importance of pathology in the multi disciplinary management of patients with these complex lesions. PMID- 26830408 TI - Radiologic Features of Sinonasal Tumors. AB - Imaging evaluation of sinonasal tumors is most often conducted with computed tomography, which excels at identifying the effects of these masses on adjacent osseous structures, and magnetic resonance imaging that is ideal for distinguishing pathologic masses from mucosal thickening and fluid that are common in the sinonasal spaces and depicting extension into the surrounding soft tissues, orbits, and intracranial compartment. Accordingly, the two studies are complementary exams and both are commonly utilized in the assessment of these masses. Less commonly, positron emission tomography can provide additional metabolic evaluation of potential metastatic disease in patients with malignant disease. While these imaging modalities are excellent for the portrayal of an abnormality, there is considerable overlap in the imaging appearance of these tumors and specific imaging manifestations linked to a particular tumor are frequently lacking. Therefore, while the mass may be readily identified, narrowing the differential diagnosis to a single specific entity is rare. Nevertheless, cross-sectional imaging plays an essential role in patient management and valuable guidance for successful biopsy or surgical resection in virtually all cases. This review emphasizes essential imaging manifestations that correlate with sinonasal tumors in general and highlight certain features that may implicate a specific disease process. PMID- 26830409 TI - Management of perianal extramammary Paget's disease involving the dentate line without abdominoperineal resection. PMID- 26830410 TI - Electrochemical and in vitro neuronal recording characteristics of multi electrode arrays surface-modified with electro-co-deposited gold-platinum nanoparticles. AB - In order to complement the high impedance electrical property of gold nanoparticles (Au NPs) we have performed electro-co-deposition of gold-platinum nanoparticles (Au-Pt NPs) onto the Au multi-electrode array (MEA) and modified the Au-Pt NPs surface with cell adhesive poly-D-lysine via thiol chemistry based covalent binding. The Au-Pt NPs were analyzed to have bimetallic nature not the mixture of Au NPs and Pt NPs by X-ray diffraction analysis and to have impedance value (4.0 * 10(4) Omega (at 1 kHz)) comparable to that of Pt NPs. The performance of Au-Pt NP-modified MEAs was also checked in relation to neuronal signal recording. The noise level in Au-Pt NP-modified MEAs was lower than in that of Au NP-modified MEA. PMID- 26830411 TI - Influence of CYP2B6 and CYP2C19 polymorphisms on sertraline metabolism in major depression patients. AB - BACKGROUND: Genetic polymorphisms in CYP2B6 and CYP2C19 may cause variability in the metabolism of sertraline, a widely used antidepressant in major depressive disorder treatment. OBJECTIVE: This study investigates the impact of CYP2B6*4 (785A > G), CYP2B6*9 (516G > T), CYP2B6*6 (516G > T + 685G > A) CYP2C19*2 (685G > A), CYP2C19*17 (-3402C > T) polymorphisms on plasma concentrations of sertraline and N-desmethyl sertraline in major depression patients treated with sertraline [n = 50]. SETTING: Participants were patients who admitted to an adult psychiatry outpatient unit at a university hospital. These were DSM-IV major depression diagnosed patients with a stable sertraline medication regimen [for at least one month]. METHODS: CYP2B6*4 (rs 2279343; 785A > G), CYP2B6*9 (516G > T; rs 3745274), CYP2B6*6 (516G > T + 685G > A) CYP2C19*2 (rs 4244285; 685G > A), CYP2C19*17 (rs 11188072; -3402C > T), polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymorphism. Plasma concentrations were measured by high-performance liquid chromatography in patients treated with SERT. MAIN OUTCOME MEASURE: The distribution of CYP2B6*4, *6, *9 and CYP2C19*2, *17 among patient group and the association between genotype and sertraline metabolism. RESULTS: Sertraline, N-desmethyl sertraline, N-desmethyl sertraline/sertraline and dose-adjusted plasma concentrations were statistically compared between individuals with wild-type and variant alleles both for CYP2B6 and CYP2C19 enzymes. The mean N-desmethyl sertraline/sertraline value, was significantly lower in all subgroups with *6 and *9 variant alleles (p < 0.05). Sertraline/C values were significantly higher (p < 0.05) and N-desmethyl sertraline/C values were lower in all subgroups with *6 and *9 variant alleles compared to wild-type subgroup. CONCLUSION: CYP2B6*6 and *9 variant alleles had a significant decreasing effect on sertraline metabolism in major depression patients which might result as variations in sertraline therapy. PMID- 26830412 TI - Information on actual medication use and drug-related problems in older patients: questionnaire or interview? AB - BACKGROUND: Information on medication use and drug-related problems is important in the preparation of clinical medication reviews. Critical information can only be provided by patients themselves, but interviewing patients is time-consuming. Alternatively, patient information could be obtained with a questionnaire. OBJECTIVE: In this study the agreement between patient information on medication use and drug-related problems in older patients obtained with a questionnaire was compared with information obtained during an interview. SETTING: General practice in The Netherlands. METHOD: A questionnaire was developed to obtain information on actual medication use and drug-related problems. Two patient groups >=65 years were selected based on general practitioner electronic medical records in nine practices; I. polypharmacy and II. >=1 predefined general geriatric problems. Eligible patients were asked to complete the questionnaire and were interviewed afterwards. MAIN OUTCOME MEASURE: Agreement on information on medication use and drug-related problems collected with the questionnaire and interview was calculated. RESULTS: Ninety-seven patients participated. Of all medications used, 87.6 % (95 % CI 84.7-90.5) was reported identically in the questionnaire and interview. Agreement for the complete medication list was found for 45.4 % (95 % CI 35.8-55.3) of the patients. On drug-related problem level, agreement between questionnaire and interview was 75 %. Agreement tended to be lower in vulnerable patients characterized by >=4 chronic diseases, >=10 medications used and low health literacy. CONCLUSION: Information from a questionnaire showed reasonable agreement compared with interviewing. The patients reported more medications and drug-related problems in the interview than the questionnaire. Taking the limitations into account, a questionnaire seems a suitable tool for medication reviews that may replace an interview for most patients. PMID- 26830413 TI - Bile duct reconstruction following laparoscopic cholecystectomy in England. AB - OBJECTIVES: To determine the incidence of bile duct reconstruction (BDR) following laparoscopic cholecystectomy (LC) and to identify associated risk factors. BACKGROUND: Major bile duct injury (BDI) requiring reconstruction is a serious complication of cholecystectomy. METHODS: All LC and attempted LC operations in England between April 2001 and March 2013 were identified. Patients with malignancy, a stone in bile duct or those who underwent bile duct exploration were excluded. This cohort of patients was followed for 1 year to identify those who underwent BDR as a surrogate marker for major BDI. Logistic regression was used to identify factors associated with the need for reconstruction. RESULTS: In total, 572,223 LC and attempted LC were performed in England between April 2001 and March 2013. Five hundred (0.09 %) of these patients underwent BDR. The risk of BDR is lower in patient that do not have acute cholecystitis [odds ratio (OR) 0.48 (95 % CI 0.30-0.76)]. The regular use of on-table cholangiography (OTC) [OR 0.69 (0.54-0.88)] and high consultant caseload >80 LC/year [OR 0.56 (0.39-0.54)] reduced the risk of BDR. Patients who underwent BDR were 10 times more likely to die within a year than those who did not require further surgery (6 vs. 0.6 %). CONCLUSIONS: The rate of BDR following laparoscopic cholecystectomy in England is low (0.09 %). The study suggests that OTC should be used more widely and provides further evidence in support of the provision of LC services by specialised teams with an adequate caseload (>80). PMID- 26830414 TI - Mechanism of Developmental Change in the PLAY Project Home Consultation Program: Evidence from a Randomized Control Trial. AB - This investigation is a secondary analysis of data from a randomized control trial of the PLAY Home Consultation Intervention Program which was conducted with 112 preschool children with Autism Spectrum Disorders and their parents (Solomon et al. in J Dev Behav Pediatr 35:475-485, 2014). Subjects were randomly assigned to either a community standard (CS) treatment group or to the PLAY Project plus CS Treatment (PLAY). PLAY subjects received monthly parent-child intervention sessions for 1 year during which parents learned how to use the rationale and interactive strategies of the Developmental, Individual-differences, Relationship based (DIR) intervention model (Greenspan and Weider in The child with special needs: encouraging intellectual and emotional growth. DeCapo Press, Cambridge, MA, 1998) to engage in more responsive, affective and less directive interactions with their children. This investigation examined whether PLAY intervention effects on parents' style of interacting with their children as well as on children's social engagement mediated the effects of PLAY on children's autism severity as measured by ADOS calibrated severity scores. Regression procedures were used to test for mediation. There were two main findings. First the effects of PLAY on children's social engagement were mediated by the increases in parental responsiveness and affect that were promoted by PLAY. Second, the effects of PLAY on the severity children's Social Affect disorders were mediated by changes in parental responsiveness and affect; however, the effects of Responsive/Affect were mediated by the impact these variables had on children's social engagement. Results are discussed in terms of contemporary models of developmental change including the developmental change model that is the foundation for DIR. PMID- 26830415 TI - Effect of oleic acid on store-operated calcium entry in immune-competent cells. AB - PURPOSE: To study the mechanism by which oleic acid (OA) (C18:1) exerts its beneficial effects on immune-competent cells. Since store-operated Ca2+ entry (SOCE) is a Ca2+ influx pathway involved in the control of multiple physiological processes including cell proliferation, we studied the effect of OA in Ca2+ signals of Jurkat T cells and THP-1 monocytes, paying particular attention to SOCE. METHODS: Changes in [Ca2+]i were measured using the Fura-2 fluorescence dye. Mn2+ uptake was monitored as a rate of quenching of Fura-2 fluorescence measured at the Ca2+-insensitive wavelengths. Thapsigargin was used to induce SOCE in Fura-2-loaded cells. RESULTS: We showed a clear dose-dependent SOCE inhibitory effect of OA in both cell lines. Such an inhibitory effect was PKC independent and totally restored by albumin, suggesting that OA exerts its effect somewhere in the membrane. We also demonstrated that OA induces increases in [Ca2+]i partly mediated by an extracellular Ca2+ influx through econazole insensitive channels. Finally, we compared the effect of OA with stearic acid (C18:0), assuming the emerged evidence concerning the link between saturated fats and inflammation disorders. Stearic acid failed to inhibit SOCE, independently on the concentration tested, thus intensifying the physiological relevance of our findings. CONCLUSION: We suggest a physiological pathway for the beneficial effects of OA in inflammation. PMID- 26830416 TI - Resistant starch for modulation of gut microbiota: Promising adjuvant therapy for chronic kidney disease patients? AB - The gut microbiota has been extensively studied in all health science fields because its imbalance is linked to many disorders, such as inflammation and oxidative stress, thereby contributing to cardiovascular disease, obesity, diabetes and chronic kidney disease (CKD) complications. Novel therapeutic strategies that aim to reduce the complications caused by this imbalance have increased in recent years. Studies have shown that prebiotic supplementation can beneficially modulate the gut microbiota in CKD patients. Prebiotics consist of non-digestible dietary soluble fiber, which acts as a substrate for the gut microbiota. Resistant starch (RS) is a type of dietary fiber that can reach the large bowel and act as a substrate for microbial fermentation; for these reasons, it has been considered to be a prebiotic. Few studies have analyzed the effects of RS on the gut microbiota in CKD patients. This review discusses recent information about RS and the potential role of the gut microbiota, with a particular emphasis on CKD patients. PMID- 26830418 TI - Current update on primary pancreatic lymphoma. AB - OBJECTIVE: This article reviews the computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) CT findings of primary and secondary pancreatic lymphomas and discusses the role of endoscopic ultrasound guided fine needle aspiration in diagnosis and management. CONCLUSION: Pancreatic lymphoma has certain characteristic imaging features which may help distinguish it from the more common pancreatic adenocarcinoma. It is critical to make an accurate diagnosis, as the management of these two conditions is vastly different. PMID- 26830417 TI - Down-regulation of NF-kappaB expression by n-3 fatty acid-rich linseed oil is modulated by PPARgamma activation, eicosanoid cascade and secretion of cytokines by macrophages in rats fed partially hydrogenated vegetable fat. AB - PURPOSE: The industrially produced partially hydrogenated vegetable fat (PHVF) contains trans fatty acid mostly comprising of elaidic acid (18:1 ?9t). PHVF is used as a cooking medium in Southeast Asian countries. The purpose of this study is to evaluate the effects of dietary PHVF on inflammatory mediators and possible ameliorative effects of n-3 fatty acid (alpha-linolenic acid, ALA)-rich linseed oil (LSO) on the inflammatory mediators. METHODS: Male Wistar weaning rats were fed AIN-93-purified diet supplemented with one of the following lipids for 60 days, groundnut oil (GNO, 10 wt%), PHVF (10 wt%), LSO (10 wt%), PHVF blended with LSO at 2.5, 5.0 and 7.5 wt% levels. The final fat level in the diet was maintained at 10 wt%. RESULTS: The macrophages from rats fed PHVF showed higher levels of total cholesterol and free cholesterol as compared to those from rats fed GNO and LSO. Macrophages from rats fed PHVF down-regulated the expression of PPARgamma and up-regulated the expressions of cytosolic phospholipase A2, cyclooxygenase-2, 5-lipoxygenase and nuclear factor-kappa B p65. The macrophages from rats fed PHVF secreted higher levels of pro-inflammatory eicosanoids and cytokines. The rats fed PHVF blended with LSO at incremental amounts showed a significant reduction in the expressions of pro-inflammatory markers in dose dependent manner. CONCLUSION: Detrimental effects of dietary PHVF in enhancing pro-inflammatory agents in rats could be significantly reduced by providing ALA (n-3 PUFA)-rich LSO. PMID- 26830419 TI - Determination of a cutoff attenuation value on single-phase contrast-enhanced CT for characterizing adrenal nodules via chemical shift MRI. AB - PURPOSE: This study aims to determine the optimal cutoff attenuation value on single-phase contrast-enhanced CT (CECT) at which chemical shift MRI (CSMRI) yields sufficient accuracy to replace the standard CT adrenal protocol for the diagnosis of adrenal adenomas. METHODS: Between January 2010 and December 2014, a total of 49 patients (age: 20-81 years; 23 men and 26 women) with 60 adrenal tumors (48 adenomas and 12 non-adenomas) who underwent both CECT in portal venous phase and CSMRI were included in the study. Attenuation on portal venous phase CECT, adrenal-to-spleen chemical shift ratio (ASR), and signal-intensity index (SII) were obtained for each adrenal mass. RESULTS: Among different cutoff values on CECT (from <70 to <120 HU), the diagnostic accuracies for those lesions measuring <80 HU were the highest and most similar to dedicated adrenal CT. The sensitivities and specificities of SII were up to 96% (25/26) and 100% (7/7) for those measuring <80 HU, but reduced to 73% (16/22) and 80% (4/5) for those >=80 HU. The overall sensitivities and specificities for diagnosing adrenal adenoma using SII vs. ASR were 85% (41/48) and 92% (11/12) vs. 71% (34/48) and 100% (12/12), respectively. CONCLUSIONS: CSMRI may replace CT adrenals in the work-up of patients with adrenal nodules below 80 HU on single-phase CECT, hence reducing radiation exposure and iodinated contrast administration. Adrenal nodules greater than 80 HU cannot be accurately diagnosed by CSMRI. CT adrenal protocol remains the appropriate investigative modality in those cases. PMID- 26830420 TI - Complementary value of pre-treatment apparent diffusion coefficient in rectal cancer for predicting tumor recurrence. AB - PURPOSE: To assess the complementary prognostic value of pre-treatment tumor apparent diffusion coefficient (ADC) for the prediction of tumor recurrence in patients with rectal cancer. METHODS: From March 2012 to March 2013, a total of 128 patients with mid/lower rectal cancer who underwent pre-treatment rectal MRI were enrolled in this retrospective study. Two radiologists in consensus evaluated conventional imaging features (Cimg) in pre-treatment rectal MRI: tumor height from anal verge (<=5 cm vs. >5 cm), T stage (high vs. low), the presence or absence of lymph node metastasis, mesorectal fascia invasion, and extramural venous invasion. The mean tumor ADC values (TumorADC) based on high b-value (0, 1000 * 10(-3) mm(2)/s) diffusion weight images were extracted. A multivariate Cox proportional hazard (CPH) regression was performed to evaluate the association of Cimg and TumorADC with the 3-year local recurrence (LR) rate. Predictive performance of two multivariate CPH models (Cimg only vs. Cimg + TumorADC) was compared using Harrell's c index (HCI). RESULTS: TumorADC (Adjusted HR, 7.830; 95% CI 3.937-15.571) and high T stage (Adjusted HR, 8.039; 95% CI 2.405-26.874) were independently associated with the 3-year LR rate. The CPH model generated with T stage + TumorADC (HCI, 0.820; 95% CI 0.708-0.932) showed significantly higher HCI than that with T stage only (HCI, 0.742; 95% CI 0.594-0.889) (P = 0.009). CONCLUSIONS: In patients with mid/lower rectal cancer, integrating TumorADC to Cimg increases predictive performance of the CPH model than that with Cimg alone for the prediction of LR within 3 years after surgery. PMID- 26830421 TI - Diagnostic performance of MDCT in identifying closed loop small bowel obstruction. AB - PURPOSE: To assess the diagnostic performance of MDCT in the diagnosis of closed loop small bowel obstruction. MATERIALS AND METHODS: One hundred fifty patients with CT reports including "small bowel obstruction (SBO)" between 1/30/2011 and 12/4/2012 were included (65 men, 85 women, mean age 63 years). CT examinations were independently and blindly reviewed by five radiologists to determine the presence of closed loop obstruction (CL-SBO) and to assess findings of bowel ischemia. Clinical records were reviewed to determine management and operative findings. Using operative findings as a gold standard, reader agreement for the diagnosis of and the CT findings associated with CLO was analyzed using Pearson's correlation (r). Positive predictive value (PPV) and negative predictive value for the diagnosis of CL-SBO and CT signs of bowel ischemia were analyzed. RESULTS: Eighty-eight of 150 patients underwent operative intervention for SBO and 24/88 were considered CL-SBO operatively. Average reader sensitivity and specificity for CL-SBO was 53 % (95 % CI 44-63 %) and 83 % (95 % CI 79-87 %). Reader agreement on CL-SBO was poor to moderate (K = 0.39-0.63). Reader agreement for CT signs of bowel ischemia resulting in a diagnosis of CL-SBO was weak (r = 0.19-0.32). CONCLUSION: The CT diagnosis of CL-SBO is complex and associated imaging findings have variable sensitivity for predicting a closed loop operative diagnosis. CT can be helpful in excluding a closed loop component in patients with SBO. PMID- 26830423 TI - First Steps in Initiating an Effective Maternal, Neonatal, and Child Health Program in Urban Slums: the BRAC Manoshi Project's Experience with Community Engagement, Social Mapping, and Census Taking in Bangladesh. AB - The processes for implementing effective programs at scale in low-income countries have not been well-documented in the peer-reviewed literature. This article describes the initial steps taken by one such program--the BRAC Manoshi Project, which now reaches a population of 6.9 million. The project has achieved notable increases in facility births and reductions in maternal and neonatal mortality. The focus of the paper is on the initial steps--community engagement, social mapping, and census taking. Community engagement began with (1) engaging local leaders, (2) creating Maternal, Neonatal, and Child Health Committees for populations of approximately 10,000 people, (3) responding to advice from the community, (4) social mapping of the community, and (5) census taking. Social mapping involved community members working with BRAC staff to map all important physical features that affect how the community carries out its daily functions- such as alleys, lanes and roads, schools, mosques, markets, pharmacies, health facilities, latrine sites, and ponds. As the social mapping progressed, it became possible to conduct household censuses with maps identifying every household and listing family members by household. Again, this was a process of collaboration between BRAC staff and community members. Thus, social mapping and census taking were also instrumental for advancing community engagement. These three processes community engagement, social mapping, and census taking--can be valuable strategies for strengthening health programs in urban slum settings of low-income countries. PMID- 26830422 TI - Economic, Legal, and Social Hardships Associated with HIV Risk among Black Men who have Sex with Men in Six US Cities. AB - We assessed whether economic, legal, and social hardships were associated with human immunodeficiency virus (HIV) risk among a sample of Black men who have sex with men (MSM) and whether associations were moderated by city of residence. The study analyzed baseline and follow-up data from HIV Prevention Trials Network 061 (N = 1553). Binary logistic regression assessed associations between hardships and HIV risk indicators. Multivariate regressions were used to test if city of residence had a moderating effect for hardships and HIV risks. Adjusted analyses showed that Black MSM with recent job loss were more likely to engage in condomless insertive anal intercourse (adjusted odds ratios (AOR) = 1.37, 95% CI 1.01-1.87) and that those with recent financial crisis were more likely to have had two or more male sexual partners in the past 6 months (AOR = 1.65; 95% CI 1.18-2.29). Black MSM with recent convictions were more likely to have a sexually transmitted infection at 6 months (AOR = 3.97; 95% CI 1.58-9.94), while those who were unstably housed were more likely to have a sexually transmitted infection at 12 months (AOR = 1.71; 95%CI 1.02 = 2.86). There were no city of residence and hardship interaction effects on HIV risks. Hardships are important factors that influence HIV risk for Black MSM. Integrating strategies that address structural factors that influence HIV risk may enhance HIV prevention interventions implementation efforts. PMID- 26830424 TI - [Personalized drug therapy based on genetics. Possibilities and examples from clinical practice]. AB - BACKGROUND: Pharmacogenetics are an important component in the individualization of treatment; however, pharmacogenetic diagnostics have so far not been used to any great extent in clinical practice. A consistent consideration of individual patient factors, such as pharmacogenetics may help to improve drug therapy and increase individual safety and efficacy aspects. OBJECTIVE: A brief summary of structures and effects of genetic variations on drug efficacy is presented. Some frequently prescribed pharmaceuticals are specified. Furthermore, the feasibility of pharmacogenetic diagnostics and dose recommendations in the clinical practice are described. CURRENT DATA: The European Medicines Agency (EMA) as the European approval authority has already extended the drug labels of more than 70 pharmaceuticals by information on pharmacogenetic biomarkers and the U.S. Food and Drug Administration (FDA) more than 150. This is a crucial step towards targeted medicine. Guidelines on dose and therapy adjustments are provided by the Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. CONCLUSION: It is fundamental to consider individual patient factors for successful drug therapy. Dose and therapy recommendations based on pharmacogenetic diagnostics are highly important for individualization as well as improvement of safety and efficiency of drug therapy. PMID- 26830425 TI - [Waldenstrom's macroglobulinemia. Current developments in diagnostics and therapy]. AB - Waldenstrom's macroglobulinemia (WM) is a rare subclass of the group of indolent B-cell lymphomas representing only 1-2 % of all hematological neoplasms. Genetic characterization of the disease allows a subdivision of WM into genotypes. The combination of rituximab and chemotherapy is still the backbone of treatment. The proteasome inhibitor bortezomib is another effective treatment option. The newly introduced oral Bruton's tyrosine kinase inhibitor ibrutinib provides an effective chemotherapy-free therapy for WM. PMID- 26830426 TI - Does Para-chloroaniline Really Form after Mixing Sodium Hypochlorite and Chlorhexidine? AB - INTRODUCTION: Mixing sodium hypochlorite (NaOCl) with chlorhexidine (CHX) forms a brown-colored precipitate. Previous studies are not in agreement whether this precipitate contains para-chloroaniline (PCA). Tests used for analysis may demonstrate different outcomes. Purpose of this study was to determine whether PCA is formed through the reaction of mixing NaOCl and CHX by using high performance liquid chromatography, proton nuclear magnetic resonance spectroscopy, gas chromatography, thin layer chromatography, infrared spectroscopy, and gas chromatography/mass spectrometry. METHODS: To obtain a brown precipitate, 4.99% NaOCl was mixed with 2.0% CHX. This brown precipitate was analyzed and compared with signals obtained from commercially available 4.99% NaOCl, 2% solutions, and 98% PCA in powder form. RESULTS: Chromatographic and spectroscopic analyses showed that brown precipitate does not contain free PCA. CONCLUSIONS: This study will be a cutoff proof for the argument on PCA formation from reaction of CHX and NaOCl. PMID- 26830427 TI - Ultrasound Stimulation of Different Dental Stem Cell Populations: Role of Mitogen activated Protein Kinase Signaling. AB - INTRODUCTION: Mesenchymal stem cells (MSCs) from dental tissues may respond to low-intensity pulsed ultrasound (LIPUS) treatment, potentially providing a therapeutic approach to promoting dental tissue regeneration. This work aimed to compare LIPUS effects on the proliferation and MAPK signaling in MSCs from rodent dental pulp stem cells (DPSCs) compared with MSCs from periodontal ligament stem cells (PDLSCs) and bone marrow stem cells (BMSCs). METHODS: Isolated MSCs were treated with 1-MHz LIPUS at an intensity of 250 or 750 mW/cm2 for 5 or 20 minutes. Cell proliferation was evaluated by 5-bromo-2-deoxyuridine (BrdU) staining after 24 hours of culture following a single LIPUS treatment. Specific ELISAs were used to determine the total and activated p38, ERK1/2, and JNK MAPK signaling proteins up to 4 hours after treatment. Selective MAPK inhibitors PD98059 (ERK1/2), SB203580 (p38), and SP600125 (JNK) were used to determine the role of activation of the particular MAPK pathways. RESULTS: The proliferation of all MSC types was significantly increased after LIPUS treatment. LIPUS at a 750 mW/cm2 dose induced the greatest effects on DPSCs. BMSC proliferation was stimulated in equal measures by both intensities, whereas 250 mW/cm2 LIPUS exposure exerted maximum effects on PDLSCs. ERK1/2 was activated immediately in DPSCs after treatment. Concomitantly, DPSC proliferation was specifically modulated by ERK1/2 inhibition, whereas p38 and JNK inhibition exerted no effects. In BMSCs, JNK MAPK signaling was LIPUS activated, and the increase in proliferation was blocked by specific inhibition of the JNK pathway. In PDLSCs, JNK MAPK signaling was activated immediately after LIPUS, whereas p-p38 MAPK increased significantly in these cells 4 hours after exposure. Correspondingly, JNK and p38 inhibition modulated LIPUS-stimulated PDLSC proliferation. CONCLUSIONS: LIPUS promoted MSC proliferation in an intensity and cell-specific dependent manner via activation of distinct MAPK pathways. PMID- 26830428 TI - Effectiveness of Different Disinfection Protocols on the Reduction of Bacteria in Enterococcus faecalis Biofilm in Teeth with Large Root Canals. AB - INTRODUCTION: This study compared the effectiveness of different disinfection protocols in reducing bacteria in an Enterococcus faecalis biofilm in teeth with large root canals. METHODS: Fifty-five roots were prepared from human mandibular premolars with large single root canals, and 50 roots were infected with E. faecalis for 21 days. Four roots were observed using scanning electron microscopy to verify biofilm formation. The remaining specimens were assigned into 5 experimental groups and a sterile control group: mechanical instrumentation using files size 60-90 and 2.5% sodium hypochlorite (NaOCl) (MI-N), irrigation with 2.5% NaOCl (IR-N), irrigation with 2.5% NaOCl using intermittent passive ultrasonic irrigation (PUI-N), irrigation with normal saline, and no intervention (initial). After root canal disinfection, dentin specimens were collected for microbial analysis. Mean colony forming units were determined and compared between groups using 1-way analysis of variance. RESULTS: The lowest number of intracanal bacteria (24.5 colony-forming units/mL) was recovered from the MI-N group followed by the PUI-N and IR-N groups. The irrigation with normal saline group did not show a significant reduction compared with the initial group. However, there were significant differences between groups (P < .01). The remaining bacteria in the PUI-N group was 4.5-fold lower compared with the IR-N group; however, it was 1862-fold higher compared with the MI-N group. CONCLUSIONS: MI-N was the most effective method to disinfect large root canals. Although ultrasonic activation enhanced the efficacy of root canal irrigation, it could not substitute for mechanical instrumentation even in large root canals with unlimited irrigant access to the apical portion. PMID- 26830429 TI - Increased ferritin levels in patients with anorexia nervosa: impact of weight gain. AB - PURPOSE: A few recent studies have found elevated ferritin levels in patients with anorexia nervosa (AN), indicating ferritin as a potential biomarker of disease severity. The purpose of this study was to study how body mass index (BMI) and changes in BMI affect plasma ferritin concentrations in Swedish patients with eating disorders. MATERIALS AND METHODS: In a retrospective computer search from 2009 to 2014, 662 patients with an eating disorder were identified from more than 200,000 individuals with electronic medical records. Three hundred and eighty-nine patients (374 females and 15 males) were found to have at least one p-ferritin value with a corresponding BMI value. Patients with AN were compared to a combined group consisting of patients with bulimia nervosa (BN) and patients with an eating disorder not otherwise specified (EDNOS). RESULTS: Patients with AN had lower BMI compared to the combined group of patients with other eating disorders (BMI = 16.5 +/- 1.5, n = 77 vs. 21.0 +/- 4.7, n = 312, p < 0.001). Patients with AN also had higher plasma ferritin levels (median 42 MUg/L (range 3.3-310) vs. 31 MUg/L (range 2.8-280); p < 0.001). As BMI increased in patients with AN, ferritin levels decreased (from a median of 40 MUg/L (7-400) to 26 (4-170), n = 47; p < 0.001). DISCUSSION: Measuring ferritin in patients with AN could be valuable in monitoring improvements of nutritional status, but the full clinical value of following ferritin in individual patients has yet to be determined. The study also shows how research can benefit from electronically captured clinical data using electronic health records. PMID- 26830430 TI - Psychotropic medications in adult and adolescent eating disorders: clinical practice versus evidence-based recommendations. AB - AIM: The current study examined the frequency of psychotropic prescriptions in a clinical sample of eating disorder (ED) patients confirming earlier research indicating their use is very common but inconsistent with evidence-based recommendations. METHODS: The sample consisted of 501 ED patients admitted to an adult partial hospitalization or adolescent residential program. Patients were divided into two diagnostic groups: anorexia nervosa (AN = 287) and bulimia nervosa (BN = 214), as well as two age groups: adults (age >=18; N = 318) and adolescents (age <18; N = 183). RESULTS: Forty-one different psychotropic medications (891 prescriptions in all) were prescribed for 429 patients. Overall, 85.6 % of the total sample reported using one or more psychotropic medications. Of 429 patients using any medications, 46.9 % were on two or more, 25.3 % on three or more, and 11.0 % four or more. Antidepressants were most commonly prescribed (89.5 % of those on medication) with no significant differences in usage patterns based on diagnosis. However, there was greater medication use among adults (89.6 %) compared to adolescents (78.7 %). Results indicate psychotropic medication prescription is more widespread in a clinical sample than in an earlier report screening for osteoporosis in AN women. DISCUSSION: Treatment recommendations suggest medication should not be the primary treatment for EDs and empirical evidence demonstrates their ineffectiveness in AN. Nevertheless, there were no differences in frequency found between diagnostic groups, confirming little relationship between evidence-based recommendations and actual clinical use for those referred to a specialized ED treatment facility. This study adds new evidence regarding age-based comparisons of psychotropic prescription frequency in clinical EDs and comparison between AN and BN which has not been examined in earlier studies. PMID- 26830431 TI - Microcirculation alterations in experimentally induced gingivitis in dogs. AB - The present study aimed to morphologically examine the gingival microvascular network using a microvascular resin cast (MRC) technique, and to investigate how inflammatory disease functionally affects gingival microcirculation using laser Doppler flowmetry (LDF). We used four beagle dogs with healthy periodontal tissue as experimental animals. To cause periodontal inflammation, dental floss was placed around the cervical neck portions of the right premolars. The unmanipulated left premolars served as controls, and received plaque control every 7 days. After 90 days, gingivitis was induced in the experimental side, while the control side maintained healthy gingiva. To perform morphological examinations, we used an MRC method involving the injection of low-viscosity synthetic resin into the blood vessels, leading to peripheral soft-tissue dissolution and permitting observation of the bone, teeth, and vascular cast. Gingival blood flow was estimated using an LDF meter. The control gingival vasculature showed hairpin-loop-like networks along the tooth surface. The blood vessels had diameters of 20-40 MUm and were regularly arranged around the cervical portion. On the other hand, the vasculature in the experimental group was twisted and gathered into spiral forms, with blood vessels that had uneven surfaces and smaller diameters of 8-10 MUm. LDF revealed reduced gingival blood flow in the group with experimentally induced gingivitis compared to controls. The actual measurements of gingival blood flow by LDF were in agreement with the alterations that would be expected based on the gingivitis-induced morphological alterations observed with the MRC technique. PMID- 26830432 TI - Pyrrolizidine Alkaloids Negatively Affect a Generalist Herbivore Feeding on the Chemically Protected Legume Crotalaria pallida. AB - Plant secondary metabolites can have opposing effects on adapted specialist and non-adapted, generalist herbivores. In this study, we used Heliothis virescens (Fabricius) (Lepidoptera: Noctuidae) as a generalist, non-adapted model herbivore to test the possible effects of Crotalaria pallida (Fabaceae: Papilionoideae) defenses on herbivore performance. Neonate H. virescens larvae were able to consume C. pallida leaves and fruits and grow for a few instars, but none of them survived to pupation. We added isolated pyrrolizidine alkaloids (PAs) to an artificial diet at different concentrations, and PA concentration significantly affected the number of larvae that achieved pupation. Larval survival was not reduced at a PA concentration similar to the concentration on green seeds of C. pallida, but it was significantly reduced at PA concentration 5 and 100 times higher. These results suggest that PAs in isolation are not the defense responsible for the mortality in fresh C. pallida plants, indicating the importance of other possible defenses. The negative effect of PAs on fitness of the non-adapted, generalist herbivore is in agreement with few previous studies, but it is in clear contrast to a previous study on the effects of PAs on the adapted specialist herbivore Utetheisa ornatrix (L.) that were able to sequester PAs with no fitness costs. PMID- 26830433 TI - Functional Process Zones Characterizing Aquatic Insect Communities in Streams of the Brazilian Cerrado. AB - Stream ecology studies see to understand ecological dynamics in lotic systems. The characterization of streams into Functional Process Zones (FPZ) has been currently debated in stream ecology because aquatic communities respond to functional processes of river segments. Therefore, we tested if different functional process zones have different number of genera and trophic structure using the aquatic insect community of Neotropical streams. We also assessed whether using physical and chemical variables may complement the approach of using FPZ to model communities of aquatic insects in Cerrado streams. This study was conducted in 101 streams or rivers from the central region of the state of Goias, Brazil. We grouped the streams into six FPZ associated to size of the river system, presence of riparian forest, and riverbed heterogeneity. We used Bayesian models to compare number of genera and relative frequency of the feeding groups between FPZs. Streams classified in different FPZs had a different number of genera, and the largest and best preserved rivers had an average of four additional genera. Trophic structure exhibited low variability among FPZs, with little difference both in the number of genera and in abundance. Using functional process zones in Cerrado streams yielded good results for Ephemeroptera, Plecoptera, and Trichoptera communities. Thus, species distribution and community structure in the river basin account for functional processes and not necessarily for the position of the community along a longitudinal dimension of the lotic system. PMID- 26830434 TI - Branch Width and Height Influence the Incorporation of Branches into Foraging Trails and Travel Speed in Leafcutter Ants Atta cephalotes (L.) (Hymenoptera: Formicidae). AB - Fallen branches are often incorporated into Atta cephalotes (L.) foraging trails to optimize leaf tissue transport rates and economize trail maintenance. Recent studies in lowlands show laden A. cephalotes travel faster across fallen branches than on ground, but more slowly ascending or descending a branch. The latter is likely because (1) it is difficult to travel up or downhill and (2) bottlenecks occur when branches are narrower than preceding trail. Hence, both branch height and width should determine whether branches decrease net travel times, but no study has evaluated it yet. Laden A. cephalotes were timed in relation to branch width and height across segments preceding, accessing, across, and departing a fallen branch in the highlands of Costa Rica. Ants traveled faster on branches than on cleared segments of trunk-trail, but accelerated when ascending or descending the branch-likely because of the absence of bottlenecks during the day in the highlands. Branch size did not affect ant speed in observed branches; the majority of which (22/24) varied from 11 to 120 mm in both height and width (average 66 mm in both cases). To determine whether ants exclude branches outside this range, ants were offered the choice between branches within this range and branches that were taller/wider than 120 mm. Ants strongly preferred the former. Our results indicate that A. cephalotes can adjust their speed to compensate for the difficulty of traveling on branch slopes. More generally, branch size should be considered when studying ant foraging efficiency. PMID- 26830435 TI - Characterization of Feeding Injuries Caused by Ceresa nigripectus Remes Lenicov (Hemiptera: Membracidae) on Alfalfa Stems. AB - Piercing-sucking insects cause mechanical and physiological injury to plants. Ceresa nigripectus Remes Lenicov is a pest of alfalfa in subtropical regions of South America and a carrier of the ArAWB phytoplasma. The aim of this study was to determine the feeding habits of this treehopper and to describe the effects of the feeding injuries on stem vascular tissues in alfalfa. Adults and nymphs of C. nigripectus inserted their stylets repeatedly girdling the stem. One week after feeding, alfalfa stems exhibited numerous feeding canals with salivary deposits, most of which reached the phloem. Two weeks after feeding, cortex and phloem cells next to the salivary sheath collapsed, mature tracheal elements became sparse and appeared with an increased cross-section area, and phenolic compounds increased in cells and cell walls compared to undamaged plants. Three weeks after feeding, an annular callus, formed by abnormal cell division and hypertrophy of preexisting cortex and vascular cambium cells, appeared immediately above the stem girdle. Parenchyma cells from the outer layers of the callus differentiated to form secondary anomalous amphicribal bundles in the wound. The aerial parts above the stem girdle eventually withered and died. PMID- 26830436 TI - Stem cells of the suture mesenchyme in craniofacial bone development, repair and regeneration. AB - The suture mesenchyme serves as a growth centre for calvarial morphogenesis and has been postulated to act as the niche for skeletal stem cells. Aberrant gene regulation causes suture dysmorphogenesis resulting in craniosynostosis, one of the most common craniofacial deformities. Owing to various limitations, especially the lack of suture stem cell isolation, reconstruction of large craniofacial bone defects remains highly challenging. Here we provide the first evidence for an Axin2-expressing stem cell population with long-term self renewing, clonal expanding and differentiating abilities during calvarial development and homeostastic maintenance. These cells, which reside in the suture midline, contribute directly to injury repair and skeletal regeneration in a cell autonomous fashion. Our findings demonstrate their true identity as skeletal stem cells with innate capacities to replace the damaged skeleton in cell-based therapy, and permit further elucidation of the stem cell-mediated craniofacial skeletogenesis, leading to revealing the complex nature of congenital disease and regenerative medicine. PMID- 26830437 TI - Camurati-Engelmann disease. PMID- 26830438 TI - Is obesity in psoriatic arthritis associated with a poorer therapeutic response and more adverse effects of treatment with an anchor drug? AB - OBJECTIVES: To assess the association between obesity, control of inflammatory activity and increased adverse effects in psoriatic arthritis (PsA) with disease modifying anti-inflammatory drugs (DMARD). METHODS: A systematic literature review was performed using MEDLINE and EMBASE databases following the guidelines of the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) consensus statement. Studies were selected if they included patients with PsA, obesity was studied as a predictive factor, and the outcome was adverse effects, including efficacy failure. Quality was assessed using an ad hoc risk of bias tool. A qualitative analysis was carried out by type of study and study population, quality and specific results. RESULTS: We found 1043 articles, discarding most of them on the basis of title and abstract. Ten articles were studied in detail and finally excluded three. The majority concluded, with statistically significant results, that in patients with PsA and treated with TNFalpha inhibitors (TNFalphai), obesity is associated with poorer chances of achieving and maintaining a minimal disease activity, higher treatment discontinuation rates, and lower skin response. Regarding conventional synthetic DMARD, a trend toward a moderate increase in transaminases with methotrexate (MTX) was observed in obese patients with PsA. CONCLUSIONS: Obesity is a negative predictor of clinical response in patients with PsA being treated with TNFalphai. Except MTX hepatotoxicity, no other adverse effects, either with TNFalphai or other drugs, were found in relation to obesity in PsA. PMID- 26830439 TI - A computational analysis of nasal vestibule morphologic variabilities on nasal function. AB - Although advances in computational modeling have led to increased understanding of nasal airflow, not much is known about the effects of normal sinonasal anatomic variabilities on nasal function. In this study, three distinct variations in the human nasal vestibule airspace that have not been previously described were identified. Computational fluid dynamics modeling of nasal airflow profile in each identified variation of nasal vestibule phenotype was conducted to assess the role of these phenotypes on nasal physiology. Three-dimensional reconstructions of the nasal geometry in sixteen subjects with normal radiographic sinonasal images were created and each respective unilateral nasal cavity was classified as Notched, Standard, or Elongated phenotype based nasal vestibule morphology. Steady state, laminar and incompressible flow simulations were performed in the nasal geometries under physiological, pressure-driven conditions with constant inspiratory pressure. Results showed that at localized regions of the unilateral nasal cavity, average resistance was significantly different among nasal vestibule phenotypes. However, global comparison from nostril to choana showed that average resistance was not significantly different across phenotypes; suggesting that with normal anatomic variations, the nose has a natural compensatory mechanism that modulates localized airflow in order to achieve a desired amount of global airflow. PMID- 26830440 TI - Anticipatory kinematics and muscle activity preceding transitions from level ground walking to stair ascent and descent. AB - The majority of fall-related accidents are during stair ambulation-occurring commonly at the top and bottom stairs of each flight, locations in which individuals are transitioning to stairs. Little is known about how individuals adjust their biomechanics in anticipation of walking-stair transitions. We identified the anticipatory stride mechanics of nine able-bodied individuals as they approached transitions from level ground walking to stair ascent and descent. Unlike prior investigations of stair ambulation, we analyzed two consecutive "anticipation" strides preceding the transitions strides to stairs, and tested a comprehensive set of kinematic and electromyographic (EMG) data from both the leading and trailing legs. Subjects completed ten trials of baseline overground walking and ten trials of walking to stair ascent and descent. Deviations relative to baseline were assessed. Significant changes in mechanics and EMG occurred in the earliest anticipation strides analyzed for both ascent and descent transitions. For stair descent, these changes were consistent with observed reductions in walking speed, which occurred in all anticipation strides tested. For stair ascent, subjects maintained their speed until the swing phase of the latest anticipation stride, and changes were found that would normally be observed for decreasing speed. Given the timing and nature of the observed changes, this study has implications for enhancing intent recognition systems and evaluating fall-prone or disabled individuals, by testing their abilities to sense upcoming transitions and decelerate during locomotion. PMID- 26830441 TI - Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma. AB - Transdifferentiation (TD) is a recent advancement in somatic cell reprogramming. The direct conversion of TD eliminates the pluripotent intermediate state to create cells that are ideal for personalized cell therapy. Here we provide evidence that TD-derived induced neural stem cells (iNSCs) are an efficacious therapeutic strategy for brain cancer. We find that iNSCs genetically engineered with optical reporters and tumouricidal gene products retain the capacity to differentiate and induced apoptosis in co-cultured human glioblastoma cells. Time lapse imaging shows that iNSCs are tumouritropic, homing rapidly to co-cultured glioblastoma cells and migrating extensively to distant tumour foci in the murine brain. Multimodality imaging reveals that iNSC delivery of the anticancer molecule TRAIL decreases the growth of established solid and diffuse patient derived orthotopic glioblastoma xenografts 230- and 20-fold, respectively, while significantly prolonging the median mouse survival. These findings establish a strategy for creating autologous cell-based therapies to treat patients with aggressive forms of brain cancer. PMID- 26830443 TI - Association between Admission Serum 25-Hydroxyvitamin D Levels and Functional Outcome of Thrombolyzed Stroke Patients. AB - BACKGROUND: 25-Hydroxyvitamin D (25(OH)D) deficiency is a frequent condition in patients who suffer a stroke, and several studies suggested that it may be associated with a poorer prognosis. The aim of this study was to investigate specifically the association between 25(OH)D levels and functional outcome at 3 months in ischemic stroke patients treated with intravenous thrombolysis. METHODS: Consecutive ischemic stroke patients who received intravenous thrombolysis were enrolled between 2010 and 2013. Baseline characteristics were collected, and serum concentrations of 25(OH)D were measured within the first 24 hours after admission and were analyzed according to the quartiles of their distribution (<25 nmol/L versus >= 25 nmol/L). Multivariable ordinal logistic regression was used to evaluate the association between 25(OH)D and 3-month functional outcome assessed by the modified Rankin score. RESULTS: Three hundred fifty-two patients were included (mean age 68.6 +/- 15.8, 50.7% women, mean 25(OH)D level 45 +/- 25 nmol/L). The characteristics of the patients only differed with regard to higher premorbid functional impairment in patients with low 25(OH)D. In univariate analysis, the risk of functional impairment in patients with low 25(OH)D levels was greater than that in patients with higher 25(OH)D levels (odds ratio [OR] 2.10, 95% confidence interval [CI]: 1.35-3.27, P = .001). This association was still observed after adjustment for confounding variables (OR 1.70, 95% CI: 1.06-2.71, P = .027). CONCLUSION: A low serum 25(OH)D level is associated with worse functional outcome in patients with acute ischemic stroke treated with intravenous thrombolysis. Further investigations are required to understand the underlying mechanisms of this association. PMID- 26830444 TI - Repeated amphetamine injections alter behavior and induce a delayed behavioral sensitization modulated by reactivity to novelty: Similarities and differences with trauma consequences. AB - Supporting our hypothesis of common biological bases for post-traumatic stress disorder (PTSD) and addiction, we recently reported that rats exposed to a single prolonged stress (SPS), a PTSD model, develop a delayed behavioral sensitization of the noradrenergic system, similar to that observed in mice after four repeated drug administrations. However, sensitization after trauma was modulated by reactivity to novelty, and this aspect that had not been explored in the addiction model. The first aim of the paper was thus to investigate the influence of reactivity to novelty on delayed behavioral sensitization in rats after four repeated amphetamine injections. Injections were either distributed over 4 days, as conducted in mouse models of addiction, or massed during a single session, reproducing SPS conditions. The second aim was to investigate whether repeated amphetamine injections have similar behavioral consequences to those induced by PTSD. Our results showed that massed amphetamine injections induced more anxiety than distributed injections, and led to avoidance of drug-associated cues avoidance, while distributed injections somewhat reduced the startle response, such as is seen in SPS. In addition, massed amphetamine injections induced a delayed behavioral sensitization clearly affected by the reactivity to novelty, reproducing results observed following exposure to traumatic events. Finally, all rats receiving repeated amphetamine injections exhibited a behavioral sensitization in response to exposure to drug-associated cues. Taken together, these data strengthen the position that drug addiction and PTSD share some common mechanisms that we tried to clarify in this paper. PMID- 26830442 TI - Withdrawal of Antithrombotic Agents and the Risk of Stroke. AB - BACKGROUND AND PURPOSE: Antithrombotic medications are effective for ischemic stroke prevention, but stoppage of these medications is associated with an increased risk of thromboembolism. The frequency of antithrombotic withdrawal in the general population is unknown. METHODS: We conducted a random phone sample of 2036 households in the Greater Cincinnati metropolitan area, representative of the stroke population by age, sex, and race, to determine the frequency of antithrombotic medication use and stoppage by physicians for medically indicated procedures. RESULTS: Sixty-two percent of survey respondents reported that they were on an antithrombotic medication. Ten percent of participants reported that they had stopped taking their medication within the past 60 days for a medically indicated intervention. Of those who stopped taking the medication, it was more common for persons taking an anticoagulant to stop their medication (20%) than those taking an antiplatelet agent (9%). Colonoscopies and orthopedic surgeries were the most common reasons for withdrawal of antiplatelet agents, whereas orthopedic and vascular surgeries were the most common reason for withdrawal of anticoagulants. CONCLUSIONS: Recommended discontinuation of antithrombotic medication for surgical or diagnostic procedures is common practice for persons in the community representative of a stroke population. Because stoppage of these medications is associated with an increased risk of thromboembolic stroke, further clinical trials are needed to determine best management practices in this setting. PMID- 26830445 TI - Validity and Reliability of the Achillometer((r)): An Ankle Dorsiflexion Measurement Device. AB - Limited ankle dorsiflexion is closely related to important foot and ankle pathologies. Various measurement devices and methods have been examined, but these have demonstrated limited validity and reliability. The purpose of the present study was to assess the validity and intra- and interobserver reliability of the Achillometer((r)). A total of 22 consecutive subjects with ankle or foot pathologies and 39 healthy participants were included. All participants were measured using the goniometer and the Achillometer((r)), a portable device used to assess ankle dorsiflexion in the weightbearing position with knee in extension. The intraclass correlation coefficient, standard error of the mean, and minimal detectable change were determined. The goniometer and Achillometer((r)) revealed high intraobserver reliability coefficients with an intraclass correlation coefficient of 0.88 (standard error of the mean 1.49, minimal detectable change 4.12) and 0.85 (standard error of the mean 1.57, minimal detectable change 4.34), respectively. The interobserver reliability of both measurement techniques ranged from 0.63 to 0.67. The Achillometer((r)) showed a strong correlation with the goniometer for both observers. In conclusion, the Achillometer((r)) is a valid measurement device to assess ankle dorsiflexion range of motion in the weightbearing position with an extended knee in a heterogeneous population. The device has good intraobserver and moderate interobserver reliability and measurement properties comparable to those of the goniometer. PMID- 26830446 TI - Graph theoretical analysis of brain connectivity in phantom sound perception. AB - Tinnitus is a phantom sound commonly thought of to be produced by the brain related to auditory deafferentation. The current study applies concepts from graph theory to investigate the differences in lagged phase functional connectivity using the average resting state EEG of 311 tinnitus patients and 256 healthy controls. The primary finding of the study was a significant increase in connectivity in beta and gamma oscillations and a significant reduction in connectivity in the lower frequencies for the tinnitus group. There also seems to be parallel processing of long-distance information between delta, theta, alpha1 and gamma frequency bands that is significantly stronger in the tinnitus group. While the network reorganizes into a more regular topology in the low frequency carrier oscillations, development of a more random topology is witnessed in the high frequency oscillations. In summary, tinnitus can be regarded as a maladaptive 'disconnection' syndrome, which tries to both stabilize into a regular topology and broadcast the presence of a deafferentation-based bottom-up prediction error as a result of a top-down prediction. PMID- 26830448 TI - Population-Attributable Fractions of Modifiable Lifestyle Factors for CKD and Mortality in Individuals With Type 2 Diabetes: A Cohort Study. AB - BACKGROUND: We quantified the impact of lifestyle and dietary modifications on chronic kidney disease (CKD) by estimating population-attributable fractions (PAFs). STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Middle aged adults with type 2 diabetes but without severe albuminuria from the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET; n=6,916). FACTORS: Modifiable lifestyle/dietary risk factors, such as physical activity, size of social network, alcohol intake, tobacco use, diet, and intake of various food items. OUTCOMES: The primary outcome was CKD, ascertained as moderate to severe albuminuria or >=5% annual decline in estimated glomerular filtration rate (eGFR) after 5.5 years. The competing risk for death was considered. PAF was defined as the proportional reduction in CKD or mortality (within 5.5 years) that would occur if exposure to a risk factor was changed to an optimal level. RESULTS: At baseline, median urinary albumin-creatinine ratio and eGFR were 6.6 (IQR, 2.9-25.0) mg/mmol and 71.5 (IQR, 58.1-85.9) mL/min/1.73m(2), respectively. After 5.5 years, 704 (32.5%) participants developed albuminuria, 1,194 (55.2%) had a >=5% annual eGFR decline, 267 (12.3%) had both, and 1,022 (14.8%) had died. Being physically active every day has PAFs of 5.1% (95% CI, 0.5%-9.6%) for CKD and 12.3% (95% CI, 4.9%-19.1%) for death. Among food items, increasing vegetable intake would have the largest impact on population health. Considering diet, weight, physical activity, tobacco use, and size of social network, exposure to less than optimum levels gives PAFs of 13.3% (95% CI, 5.5%-20.9%) for CKD and 37.5% (95% CI, 27.8%-46.7%) for death. For the 17.8 million middle-aged Americans with diabetes, improving 1 of these lifestyle behaviors to the optimal range could reduce the incidence or progression of CKD after 5.5 years by 274,000 and the number of deaths within 5.5 years by 405,000. LIMITATIONS: Ascertainment of changes in kidney measures does not precisely match the definitions for incidence or progression of CKD. CONCLUSIONS: Healthy lifestyle and diet are associated with less CKD and mortality and may have a substantial impact on population kidney health. PMID- 26830447 TI - Abrupt Decline in Kidney Function Before Initiating Hemodialysis and All-Cause Mortality: The Chronic Renal Insufficiency Cohort (CRIC) Study. AB - BACKGROUND: It is not clear whether the pattern of kidney function decline in patients with chronic kidney disease (CKD) may relate to outcomes after reaching end-stage renal disease (ESRD). We hypothesize that an abrupt decline in kidney function prior to ESRD predicts early death after initiating maintenance hemodialysis therapy. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: The Chronic Renal Insufficiency Cohort (CRIC) Study enrolled men and women with mild to moderate CKD. For this study, we studied 661 individuals who developed chronic kidney failure that required hemodialysis therapy initiation. PREDICTORS: The primary predictor was the presence of an abrupt decline in kidney function prior to ESRD. We incorporated annual estimated glomerular filtration rates (eGFRs) into a mixed-effects model to estimate patient-specific eGFRs at 3 months prior to initiation of hemodialysis therapy. Abrupt decline was defined as having an extrapolated eGFR>=30mL/min/1.73m(2) at that time point. OUTCOMES: All-cause mortality within 1 year after initiating hemodialysis therapy. MEASUREMENTS: Multivariable Cox proportional hazards. RESULTS: Among 661 patients with CKD initiating hemodialysis therapy, 56 (8.5%) had an abrupt predialysis decline in kidney function and 69 died within 1 year after initiating hemodialysis therapy. After adjustment for demographics, cardiovascular disease, diabetes, and cancer, abrupt decline in kidney function was associated with a 3-fold higher risk for death within the first year of ESRD (adjusted HR, 3.09; 95% CI, 1.65-5.76). LIMITATIONS: Relatively small number of outcomes; infrequent (yearly) eGFR determinations; lack of more granular clinical data. CONCLUSIONS: Abrupt decline in kidney function prior to ESRD occurred in a significant minority of incident hemodialysis patients and predicted early death in ESRD. PMID- 26830449 TI - RACK1 promotes maintenance of morphine-associated memory via activation of an ERK CREB dependent pathway in hippocampus. AB - Existence of long-term drug-associated memories may be a crucial factor in drug cravings and relapse. RACK1 plays a critical role in morphine-induced reward. In the present study, we used conditioned place preference (CPP) to assess the acquisition and maintenance of morphine conditioned place preference memory. The hippocampal protein level of RACK1 and synaptic quantitation were evaluated by Western blotting, immunohistochemistry and electron microscopy, respectively. Additionally, shRACK1 (shGnb2l1) was used to silence RACK1 in vivo to evaluate the role and the underlying mechanism of RACK1 in maintenance of morphine CPP memory. We found that morphine induced CPP was maintained for at least 7 days after the last morphine treatment, which indicated a positive correlation with hippocampal RACK1 level, and was accompanied simultaneously by increases in the synapse density and hippocampal expression of synaptophysin (SYP), phosphorylation of extracellular signal-regulated kinase1/2 (pERK1/2) and the phosphorylation of cyclic adenosine monophosphate response element-binding (pCREB). ShGnb2l1 icv injection significantly suppressed the expression of all above proteins, decreased the synapse density in the hippocampus and attenuated the acquisition and maintenance of morphine CPP. Our present study highlights that RACK1 plays an important role in the maintenance of morphine CPP, likely via activation of ERK-CREB pathway in hippocampus. PMID- 26830450 TI - Leukotriene E4 is a full functional agonist for human cysteinyl leukotriene type 1 receptor-dependent gene expression. AB - Leukotriene E4 (LTE4) the most stable of the cysteinyl leukotrienes (cysLTs) binds poorly to classical type 1 (CysLT1) and 2 (CysLT2) receptors although it induces potent responses in human airways in vivo, such as bronchoconstriction, airway hyperresponsiveness and inflammatory cell influx suggesting the presence of a novel receptor that preferentially responds to LTE4. To identify such a receptor two human mast cell lines, LAD2 and LUVA, were selected that differentially responded to LTE4 when analysed by intracellular signalling and gene expression. Comparative transcriptome analysis and recombinant gene overexpression experiments revealed CysLT1 as a receptor responsible for potent LTE4-induced response in LAD2 but not in LUVA cells, an observation confirmed further by gene knockdown and selective inhibitors. Lentiviral overexpression of CysLT1 in LUVA cells augmented intracellular calcium signalling induced by LTE4 but did not restore full agonist responses at the gene expression level. Our data support a model where both an increased expression of Galphaq-coupled CysLT1, and sustained intracellular calcium mobilisation and extracellular signal-regulated kinase (Erk) activation, are required for LTE4-mediated regulation of gene expression in human cells. Our study shows for the first time that CysLT1 expression is critically important for responsiveness to LTE4 within a human cell system. PMID- 26830451 TI - DNA damage markers in dermal fibroblasts in vitro reflect chronological donor age. AB - The aging process is accompanied by an accumulation of cellular damage, which compromises the viability and function of cells and tissues. We aim to further explore the association between in vitro DNA damage markers and the chronological age of the donor, as well as long-lived family membership and presence of cardiovascular diseases. Therefore, numbers of 53BP1 foci, telomere-associated foci (TAF) and micronuclei were measured in cultured dermal fibroblasts obtained from three age groups of donors (mean age 22, 63 and 90 years). Fibroblasts were cultured without a stressor and with 0.6 MUM rotenone for 3 days. We found that 53BP1 foci and TAF were more frequently present in fibroblasts of old donors compared to middle-aged and young donors. No association between micronuclei and donor age was found. Within the fibroblasts of the middle-aged donors we did not find associations between DNA damage markers and long-lived family membership or cardiovascular disease. Results were comparable when fibroblasts were stressed in vitro with rotenone. In conclusion, we found that DNA damage foci of cultured fibroblasts are significantly associated with the chronological age, but not biological age, of the donor. PMID- 26830452 TI - Multiple exciton generation induced enhancement of the photoresponse of pulsed laser-ablation synthesized single-wall-carbon-nanotube/PbS-quantum-dots nanohybrids. AB - The pulsed laser deposition method was used to decorate appropriately single wall carbon nanotubes (SWCNTs) with PbS quantum dots (QDs), leading to the formation of a novel class of SWCNTs/PbS-QDs nanohybrids (NHs), without resorting to any ligand engineering and/or surface functionalization. The number of laser ablation pulses (NLp) was used to control the average size of the PbS-QDs and their coverage on the SWCNTs' surface. Photoconductive (PC) devices fabricated from these SWCNTs/PbS-QDs NHs have shown a significantly enhanced photoresponse, which is found to be PbS-QD size dependent. Wavelength-resolved photocurrent measurements revealed a strong photoconductivity of the NHs in the UV-visible region, which is shown to be due to multiple exciton generation (MEG) in the PbS QDs. For the 6.5 nm-diameter PbS-QDs (with a bandgap (Eg) = 0.86 eV), the MEG contribution of the NHs based PC devices was shown to lead to a normalized internal quantum efficiency in excess of 300% for photon energies >=4.5Eg. While the lowest MEG threshold in our NHs based PC devices is found to be of ~2.5Eg, the MEG efficiency reaches values as high as 0.9 +/- 0.1. PMID- 26830453 TI - Study design requirements for RNA sequencing-based breast cancer diagnostics. AB - Sequencing-based molecular characterization of tumors provides information required for individualized cancer treatment. There are well-defined molecular subtypes of breast cancer that provide improved prognostication compared to routine biomarkers. However, molecular subtyping is not yet implemented in routine breast cancer care. Clinical translation is dependent on subtype prediction models providing high sensitivity and specificity. In this study we evaluate sample size and RNA-sequencing read requirements for breast cancer subtyping to facilitate rational design of translational studies. We applied subsampling to ascertain the effect of training sample size and the number of RNA sequencing reads on classification accuracy of molecular subtype and routine biomarker prediction models (unsupervised and supervised). Subtype classification accuracy improved with increasing sample size up to N = 750 (accuracy = 0.93), although with a modest improvement beyond N = 350 (accuracy = 0.92). Prediction of routine biomarkers achieved accuracy of 0.94 (ER) and 0.92 (Her2) at N = 200. Subtype classification improved with RNA-sequencing library size up to 5 million reads. Development of molecular subtyping models for cancer diagnostics requires well-designed studies. Sample size and the number of RNA sequencing reads directly influence accuracy of molecular subtyping. Results in this study provide key information for rational design of translational studies aiming to bring sequencing-based diagnostics to the clinic. PMID- 26830454 TI - A micro-scale simulation of red blood cell passage through symmetric and asymmetric bifurcated vessels. AB - Blood exhibits a heterogeneous nature of hematocrit, velocity, and effective viscosity in microcapillaries. Microvascular bifurcations have a significant influence on the distribution of the blood cells and blood flow behavior. This paper presents a simulation study performed on the two-dimensional motions and deformation of multiple red blood cells in microvessels with diverging and converging bifurcations. Fluid dynamics and membrane mechanics were incorporated. Effects of cell shape, hematocrit, and deformability of the cell membrane on rheological behavior of the red blood cells and the hemodynamics have been investigated. It was shown that the blood entering the daughter branch with a higher flow rate tended to receive disproportionally more cells. The results also demonstrate that red blood cells in microvessels experienced lateral migration in the parent channel and blunted velocity profiles in both straight section and daughter branches, and this effect was influenced by the shape and the initial position of the cells, the hematocrit, and the membrane deformability. In addition, a cell free region around the tip of the confluence was observed. The simulation results are qualitatively consistent with existing experimental findings. This study may provide fundamental knowledge for a better understanding of hemodynamic behavior of micro-scale blood flow. PMID- 26830455 TI - A review of the interactions between acrylamide, microorganisms and food components. AB - Acrylamide (AA) and its metabolites have been recognized as potential carcinogens, but also they can cause other negative symptoms in human or animal organisms and therefore this class of chemical compounds has attracted a lot of attention. These substances are usually formed when heating asparagine in the presence of compounds that have alpha-hydroxycarbonyl groups, alpha,beta,gamma,delta-diunsaturated carbonyl groups or alpha-dicarbonyl groups. The acrolein pathway and enzymatic decarboxylation of asparagine, as well as endogenic processes, are other alternative routes to AA formation. It has been demonstrated that the animal model used for examining AA toxicity may not be sufficient to investigate these changes in humans, therefore it is necessary to design an in vitro model, which could provide more accurate insights into the direction of these processes in human organisms. Acrylamide can be metabolized through both oxidative and reductive pathways; moreover, there is also a chance that some representatives of intestinal microbiota are able to transform acrylamide. It was shown that there are various microorganisms, mostly bacteria, that produce amidases, i.e. enzymes decomposing AA. Lactic acid bacteria also appear to demonstrate the ability to use acrylamide as a carbon source, but this still requires further investigation. Another way to prevent AA toxicity is related to the presence of some food compounds, such as certain proteins or polyphenols. There are still lot of gaps in the current knowledge related to AA toxicity, so future potential research directions are presented in this review as well. PMID- 26830456 TI - Surprising impact of remote groups on the folding--unfolding and dimer-chain equilibria of bifunctional H-bonding unimers. AB - Oligoamide 1, consisting of two H-bonding units linked by a trimethylene linker, was previously found to form a very stable, folded dimer. In this work, replacing the side chains and end groups of 1 led to derivatives that show the surprising impact of end groups on the folding and dimer-chain equilibria of the resultant molecules. PMID- 26830457 TI - Universal conformational properties of polymers in ionic nanogels. AB - Polyelectrolyte gels are known to undergo significant conformational changes in response to external stimuli such as pH, temperature, or the dielectric constant. Specifically, an increase of the degree of ionization associated with an increasing number of counterions leads to swelling of the network. For a macroscopically large gel, which is electrostatically neutral in its interior, swelling is no longer governed by electrostatic interactions, but rather by the osmotic pressure of counterions. However, this electrostatic neutrality is typically violated for nanogels, because counterions are free to leave a gel particle. Although nanogel-swelling exhibits similar features as swelling of micro- and macrogels, another mechanism has to be relevant. Here, we use molecular dynamics simulations and scaling theory to unravel the structural properties of nanogels upon changing the electrostatic interactions. We demonstrate that the swelling of nanogels is governed by screened electrostatic interactions without a relevant contribution by the counterion osmotic pressure. PMID- 26830458 TI - New approaches to evaluating complex health and care systems. PMID- 26830459 TI - Sprouty1 haploinsufficiency accelerates pheochromocytoma development in Pten+/- mice. PMID- 26830460 TI - Correlated magnetic resonance imaging and ultramicroscopy (MR-UM) is a tool kit to assess the dynamics of glioma angiogenesis. AB - Neoangiogenesis is a pivotal therapeutic target in glioblastoma. Tumor monitoring requires imaging methods to assess treatment effects and disease progression. Until now mapping of the tumor vasculature has been difficult. We have developed a combined magnetic resonance and optical toolkit to study neoangiogenesis in glioma models. We use in vivo magnetic resonance imaging (MRI) and correlative ultramicroscopy (UM) of ex vivo cleared whole brains to track neovascularization. T2* imaging allows the identification of single vessels in glioma development and the quantification of neovessels over time. Pharmacological VEGF inhibition leads to partial vascular normalization with decreased vessel caliber, density, and permeability. To further resolve the tumor microvasculature, we performed correlated UM of fluorescently labeled microvessels in cleared brains. UM resolved typical features of neoangiogenesis and tumor cell invasion with a spatial resolution of ~5 um. MR-UM can be used as a platform for three dimensional mapping and high-resolution quantification of tumor angiogenesis. PMID- 26830461 TI - A mathematical model explains saturating axon guidance responses to molecular gradients. AB - Correct wiring is crucial for the proper functioning of the nervous system. Molecular gradients provide critical signals to guide growth cones, which are the motile tips of developing axons, to their targets. However, in vitro, growth cones trace highly stochastic trajectories, and exactly how molecular gradients bias their movement is unclear. Here, we introduce a mathematical model based on persistence, bias, and noise to describe this behaviour, constrained directly by measurements of the detailed statistics of growth cone movements in both attractive and repulsive gradients in a microfluidic device. This model provides a mathematical explanation for why average axon turning angles in gradients in vitro saturate very rapidly with time at relatively small values. This work introduces the most accurate predictive model of growth cone trajectories to date, and deepens our understanding of axon guidance events both in vitro and in vivo. PMID- 26830462 TI - Dopamine regulates stimulus generalization in the human hippocampus. AB - The ability to generalize previously learned information to novel situations is fundamental for adaptive behavior. However, too wide or too narrow generalization is linked to neuropsychiatric disorders. Previous research suggests that interactions between the dopaminergic system and the hippocampus may play a role in generalization, but whether and how the degree of generalization can be modulated via these pathways is currently unknown. Here, we addressed this question in humans using pharmacology, functional magnetic resonance imaging, and computational modeling. Blocking dopamine D2-receptors (D2R) altered generalization behavior as revealed by an increased kurtosis of the generalization gradient, and a decreased width of model-derived generalization parameters. Moreover, D2R-blockade modulated similarity-based responses in the hippocampus and decreased midbrain-hippocampal connectivity, which in turn correlated with individual differences in generalization. These results suggest that dopaminergic activity in the hippocampus may relate to the degree of generalization and highlight a potential target for treatment. PMID- 26830464 TI - Enhanced waste activated sludge digestion using a submerged anaerobic dynamic membrane bioreactor: performance, sludge characteristics and microbial community. AB - Anaerobic digestion (AD) plays an important role in waste activated sludge (WAS) treatment; however, conventional AD (CAD) process needs substantial improvements, especially for the treatment of WAS with low solids content and poor anaerobic biodegradability. Herein, we propose a submerged anaerobic dynamic membrane bioreactor (AnDMBR) for simultaneous WAS thickening and digestion without any pretreatment. During the long-term operation, the AnDMBR exhibited an enhanced sludge reduction and improved methane production over CAD process. Moreover, the biogas generated in the AnDMBR contained higher methane content than CAD process. Stable carbon isotopic signatures elucidated the occurrence of combined methanogenic pathways in the AnDMBR process, in which hydrogenotrophic methanogenic pathway made a larger contribution to the total methane production. It was also found that organic matter degradation was enhanced in the AnDMBR, thus providing more favorable substrates for microorganisms. Pyrosequencing revealed that Proteobacteria and Bacteroidetes were abundant in bacterial communities and Methanosarcina and Methanosaeta in archaeal communities, which played an important role in the AnDMBR system. This study shed light on the enhanced digestion of WAS using AnDMBR technology. PMID- 26830465 TI - The occurrence of the filarial nematode Dirofilaria repens in canine hosts from Maio Island, Cape Verde. AB - The prevalence of canine Dirofilaria infection in Maio Island (Cape Verde) was analysed by serology, morphological and molecular identification of the parasite species. Blood and sera were collected from 150 dogs and 80 cats aged over 6 months from various localities of the island. DNA was extracted from blood and samples were screened by polymerase chain reaction (PCR) using microfilaria specific primers. No Dirofilaria immitis was found in dogs while D. repens microfilariae were found in 5.3% of dogs and 6% were positive by PCR. The species identity was confirmed by sequencing of PCR products, which showed almost 100% homology with D. repens European sequences published in GenBank. No difference in Dirofilaria infection was observed between males and females or in dogs with different weights. However, older dogs and those from the western part of Maio Island were more frequently infected. No Dirofilaria was found in cats. This study represents the first evidence of D. repens in Cape Verde (West Africa) and highlights the need for implementing control measures and for a better surveillance of dirofilariosis in Africa. PMID- 26830463 TI - Fibroblastic reticular cell-derived lysophosphatidic acid regulates confined intranodal T-cell motility. AB - Lymph nodes (LNs) are highly confined environments with a cell-dense three dimensional meshwork, in which lymphocyte migration is regulated by intracellular contractile proteins. However, the molecular cues directing intranodal cell migration remain poorly characterized. Here we demonstrate that lysophosphatidic acid (LPA) produced by LN fibroblastic reticular cells (FRCs) acts locally to LPA2 to induce T-cell motility. In vivo, either specific ablation of LPA producing ectoenzyme autotaxin in FRCs or LPA2 deficiency in T cells markedly decreased intranodal T cell motility, and FRC-derived LPA critically affected the LPA2-dependent T-cell motility. In vitro, LPA activated the small GTPase RhoA in T cells and limited T-cell adhesion to the underlying substrate via LPA2. The LPA LPA2 axis also enhanced T-cell migration through narrow pores in a three dimensional environment, in a ROCK-myosin II-dependent manner. These results strongly suggest that FRC-derived LPA serves as a cell-extrinsic factor that optimizes T-cell movement through the densely packed LN reticular network. PMID- 26830466 TI - One-Step Fabrication of Stretchable Copper Nanowire Conductors by a Fast Photonic Sintering Technique and Its Application in Wearable Devices. AB - Copper nanowire (CuNW) conductors have been considered to have a promising perspective in the area of stretchable electronics due to the low price and high conductivity. However, the fabrication of CuNW conductors suffers from harsh conditions, such as high temperature, reducing atmosphere, and time-consuming transfer step. Here, a simple and rapid one-step photonic sintering technique was developed to fabricate stretchable CuNW conductors on polyurethane (PU) at room temperature in air environment. It was observed that CuNWs were instantaneously deoxidized, welded and simultaneously embedded into the soft surface of PU through the one-step photonic sintering technique, after which highly conductive network and strong adhesion between CuNWs and PU substrates were achieved. The CuNW/PU conductor with sheet resistance of 22.1 Ohm/sq and transmittance of 78% was achieved by the one-step photonic sintering technique within only 20 MUs in air. Besides, the CuNW/PU conductor could remain a low sheet resistance even after 1000 cycles of stretching/releasing under 10% strain. Two flexible electronic devices, wearable sensor and glove-shaped heater, were fabricated using the stretchable CuNW/PU conductor, demonstrating that our CuNW/PU conductor could be integrated into various wearable electronic devices for applications in food, clothes, and medical supplies fields. PMID- 26830467 TI - Endothelial activation, haemostasis and thrombosis biomarkers in Ugandan children with severe malaria participating in a clinical trial. AB - BACKGROUND: Malaria is a major cause of morbidity and mortality in sub-Saharan Africa, and poor outcomes have been associated with endothelial activation. In this study, biomarkers of endothelial activation, haemostasis, and thrombosis were measured in Ugandan children with severe malaria who participated in a clinical trial, in order to investigate associations between these processes. METHODS: Serum and plasma were collected from participants at baseline (day 1), and on days 2, 3, 4, and 14. Von Willebrand factor (VWF) antigen was measured in stored plasma samples from all trial participants, and its association with mortality and changes over time were analysed. VWF multimer patterns were evaluated in baseline serum samples by gel electrophoresis followed by Western blotting. Levels of angiopoietins 1 and 2, VWF antigen, total active VWF, ADAMTS13, platelet counts, apolipoprotein A1, and syndecan-1 were measured in stored serum samples from 12 survivors at baseline and day 4. RESULTS: VWF antigen levels were associated with mortality, and decreased over time in survivors. Baseline VWF antigen and total active VWF levels were elevated, and very large multimers were present in the baseline serum of several patients. Higher platelet counts were associated with higher angiopoietin-1 and apolipoprotein A1 levels, while lower platelet counts were associated with higher syndecan-1, a marker of endothelial damage. Higher angiopoietin-2 to angiopoietin 1 ratio and higher syndecan-1 levels were correlated with lower apolipoprotein A1 levels. There were no correlations between total active VWF, VWF antigen, or ADAMTS13 levels and the other biomarkers at baseline. Changes in biomarker levels between baseline and day 4 were not correlated. CONCLUSIONS: These results confirm that severe malaria is associated with endothelial activation, and suggest that endothelial activation contributes to microvascular thrombosis and endothelial damage. PMID- 26830468 TI - A phase 1 randomized, double-blind, placebo-controlled, crossover trial of DAS181 (Fludase(r)) in adult subjects with well-controlled asthma. AB - BACKGROUND: Influenza virus (IFV) infection is associated with increased morbidity and mortality in people with underlying lung disease. Treatment options for IFV are currently limited and antiviral resistance is a growing concern. DAS181, an inhaled antiviral with a unique mechanism of action, has shown promise in early clinical trials involving generally healthy human subjects. This study was undertaken to assess the safety and tolerability of DAS181 in individuals with underlying reactive airway disease. METHODS: This was a randomized, double blind, placebo-controlled, crossover phase 1 study of DAS181-F02. Dry particle inhaler administration of 10 mg was done on 3 consecutive days in ten adult volunteers with well-controlled asthma. The primary outcome was the frequency of adverse events (AEs), grade 1 or higher that occurred during each study period. RESULTS: There were 280 AEs among ten evaluable subjects (56.8 % active; 43.2 % placebo); 90.7 % were grade 1. No grade 3 or higher AEs occurred. A statistically significant association between exposure to DAS181 and experiencing any AE, a grade 1 AE, or a grade 2 AE was not detected. Overall, the majority of AEs were classified as possibly related (35.7 %), unlikely related (38.9 %), or unrelated (15.4 %) to study drug administration. However, there was a statistically significant association between exposure to DAS181 and experiencing a definitely or probably related AE. Respiratory effects, including dyspnea, dry cough, and chest discomfort related to respirations, accounted for all of the definitely related AEs and one of the most common probably related AEs. CONCLUSIONS: DAS181 was safe in this small study of otherwise healthy subjects with well-controlled asthma. However, the generalizability of these results is limited by the small sample size and generally mild nature of the subjects' asthma at baseline. The increased association of respiratory events classified as probably or definitely related to DAS181 administration suggests caution may need to be employed when administering DAS181 to individuals with less stable reactive airway disease. Further investigation in a controlled setting of the safety and efficacy of DAS181 in a larger population of asthmatic subjects with varying disease activity is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT01113034 Trial Registration Date: April 27, 2010. PMID- 26830469 TI - Influence of Nanomaterial Compatibilization Strategies on Polyamide Nanocomposites Properties and Nanomaterial Release during the Use Phase. AB - The incorporation of small amounts of nanofillers in polymeric matrices has enabled new applications in several industrial sectors. The nanofiller dispersion can be improved by modifying the nanomaterial (NM) surface or predispersing the NMs to enhance compatibility. This study evaluates the effect of these compatibilization strategies on migration/release of the nanofiller and transformation of polyamide-6 (PA6), a thermoplastic polymer widely used in industry during simulated outdoors use. Two nanocomposites (NCs) containing SiO2 nanoparticles (NPs) with different surface properties and two multiwalled carbon nanotube (MWCNT) NCs obtained by different addition methods were produced and characterized, before and after accelerated wet aging conditions. Octyl-modified SiO2 NPs, though initially more aggregated than uncoated SiO2 NPs, reduced PA6 hydrolysis and, consequently, NM release. Although no clear differences in dispersion were observed between the two types of MWCNT NCs (masterbatch vs direct addition) after manufacture, the use of the MWCNT masterbatch reduced PA6 degradation during aging, preventing MWCNT accumulation on the surface and further release or potential exposure by direct contact. The amounts of NM released were lower for MWCNTs (36 and 108 mg/m(2)) than for SiO2 NPs (167 and 730 mg/m(2)), being lower in those samples where the NC was designed to improve the nanofiller-matrix interaction. Hence, this study shows that optimal compatibilization between NM and matrix can improve NC performance, reducing polymer degradation and exposure and/or release of the nanofiller. PMID- 26830470 TI - A qualitative study in parental perceptions and understanding of SIDS-reduction guidance in a UK bi-cultural urban community. AB - BACKGROUND: Differences in both Sudden Infant Death Syndrome (SIDS) rates and infant care practices between white British and South Asians in UK are well known, but research has not yet examined how these two groups understand and implement SIDS-reduction guidance. This study aimed to discover how white British and Pakistani mothers in Bradford recall, understand and interpret SIDS-reduction guidance, and to explore whether and how they implement this guidance in caring for their infants. METHODS: In-depth narrative interviews with 46 mothers (25 white British origin and 21 Pakistani origin) of 8-12 week old infants recruited from the pool of participants enrolled in the 'Born in Bradford' (BiB) cohort study. RESULTS: All mothers were aware of UK SIDS-reduction guidance from leaflets presented to them during antenatal or postnatal interactions with health care providers. Pakistani mothers tended to dismiss the guidance in toto as being irrelevant to their cultural practices; white British mothers dismissed, adapted and adopted aspects of the guidance to suit their preferred parenting decisions and personal circumstances. Many mothers misunderstood or misinterpreted the guidance given and explained their infant care behaviour according to their social and cultural circumstances. CONCLUSIONS: Current SIDS reduction information in the UK does not meet the needs of immigrant families, and is easily misinterpreted or misunderstood by mothers from all sections of the community. Tailored information acknowledging cultural differences in infant care practices is vital, as is greater discussion with all mothers about the reasons for SIDS reduction guidance. PMID- 26830471 TI - The paediatric change laboratory: optimising postgraduate learning in the outpatient clinic. AB - BACKGROUND: This study aimed to analyse and redesign the outpatient clinic in a paediatric department. The study was a joint collaboration with the doctors of the department (paediatric residents and specialists) using the Change Laboratory intervention method as a means to model and implement change in the outpatient clinic. This study was motivated by a perceived failure to integrate the activities of the outpatient clinic, patient care and training of residents. The ultimate goal of the intervention was to create improved care for patients through resident learning and development. METHODS: We combined the Change Laboratory intervention with an already established innovative process for residents, 3-h meetings. The Change Laboratory intervention method consists of a well-defined theory (Cultural-historical activity theory) and concrete actions where participants construct a new theoretical model of the activity, which in this case was paediatric doctors' workplace learning modelled in order to improve medical social practice. The notion of expansive learning was used during the intervention in conjunction with thematic analysis of data in order to fuel the process of analysis and intervention. RESULTS: The activity system of the outpatient clinic can meaningfully be analysed in terms of the objects of patient care and training residents. The Change Laboratory sessions resulted in a joint action plan for the outpatient clinic structured around three themes: (1) Before: Preparation, expectations, and introduction; (2) During: Structural context and resources; (3) After: Follow-up and feedback. The participants found the Change Laboratory method to be a successful way of sharing reflections on how to optimise the organisation of work and training with patient care in mind. CONCLUSIONS: The Change Laboratory approach outlined in this study succeeded to change practices and to help medical doctors redesigning their work. Participating doctors must be motivated to uncover inherent contradictions in their medical activity systems of which care and learning are both part. Facilitators must be willing to spend time analysing both historical paediatric practice, current data on practice, and steer clear of organisational issues that might hamper a transformative learning environment. To ensure long-term success, economical and organisational resources, participant buy-in and department leadership support play a major role. PMID- 26830472 TI - Epitelial-to-mesenchimal transition and invasion are upmodulated by tumor expressed granzyme B and inhibited by docosahexaenoic acid in human colorectal cancer cells. AB - BACKGROUND: Granzyme B (GrB) is a serine protease, traditionally known as expressed by cytotoxic lymphocytes to induce target cell apoptosis. However, it is emerging that GrB, being also produced by a variety of normal and neoplastic cells and potentially acting on multiple targets, might represent a powerful regulator of a wide range of fundamental biological processes. We have previously shown that GrB is expressed in urothelial carcinoma tissues and its expression is associated to both pathological tumor spreading and EMT. We have also shown that docosahexaenoic acid (DHA), a dietary omega-3 polyunsaturated fatty acid with anti-tumor activity, while inhibiting urothelial and pancreatic carcinoma cell invasion also inhibited their GrB expression in vitro. In this study, we characterized a panel of colorectal carcinoma (CRC) cells, with different invasive capabilities, for GrB expression and for the contribution of GrB to their EMT and invasive phenotype. In addition, we investigated the effect of DHA on CRC cell-associated GrB expression, EMT and invasion. METHODS: The expression levels of GrB and EMT-related markers were evaluated by Western blotting. GrB knockdown was performed by Stealth RNAi small interfering RNA silencing and ectopic GrB expression by transfection of human GrB vector. Cell invasion was determined by the BioCoat Matrigel invasion chamber test. RESULTS: GrB was produced in 57.1% CRC cell lines and 100% CRC-derived Cancer Stem Cells. Although GrB was constitutive expressed in both invasive and noninvasive CRC cells, GrB depletion in invasive CRC cells downmodulated their invasion in vitro, suggesting a contribution of GrB to CRC invasiveness. GrB loss or gain of function downmodulated or upmodulated EMT, respectively, according to the analysis of cancer cell expression of three EMT biomarkers (Snail1, E-cadherin, N-cadherin). Moreover, TGF-beta1-driven EMT was associated to the enhancement of GrB expression in CRC cell lines, and GrB depletion led to downmodulation of TGF beta1-driven EMT. In addition, DHA inhibited GrB expression, EMT and invasion in CRC cells in vitro. CONCLUSIONS: These findings present a novel role for GrB as upmodulator of EMT in CRC cells. Moreover, these results support the use of DHA, a dietary compound without toxic effects, as adjuvant in CRC therapy. PMID- 26830474 TI - Use of the GlideScope(r)-Ranger for pre-hospital intubations by anaesthesia trained emergency physicians - an observational study. AB - BACKGROUND: Pre-hospital endotracheal intubation is more difficult than in the operating room (OR). Therefore, enhanced airway management devices such as video laryngoscopes may be helpful to improve the success rate of pre-hospital intubation. We describe the use of the Glidescope(r)-Ranger (GS-R) as an alternative airway tool used at the discretion of the emergency physician (EP) in charge. METHODS: During a 3.5 year period, the GS-R was available to be used either as the primary or backup tool for pre-hospital intubation by anaesthesia trained EP with limited expertise using angulated videolaryngoscopes. RESULTS: During this period 672 patients needed pre-hospital intubation of which the GS-R was used in 56 cases. The overall GS-R success rate was 66 % (range of 34-100 % among EP). The reasons for difficulties or failure included inexperience of the EP with the GS-R, impaired view due to secretion, vomitus, blood or the inability to see the screen in very bright environment due to sunlight. CONCLUSION: Special expertise and substantial training is needed to successfully accomplish tracheal intubation with the GS-R in the pre-hospital setting. Providers inexperienced with DL as well as video-assisted intubation should not expect to be able to perform tracheal intubation easily just because a videolaryngoscope is available. Additionally, indirect laryngoscopy might be difficult or even impossible to achieve in the pre-hospital setting due to impeding circumstances such as blood, secretions or bright sun-light. Therefore, videolaryngoscopes, here the GS-R, should not be considered as the "Holy Grail" of endotracheal intubation, neither for the experts nor for inexperienced providers. PMID- 26830473 TI - BET protein inhibitor JQ1 inhibits growth and modulates WNT signaling in mesenchymal stem cells. AB - BACKGROUND: Efficacy and safety of anticancer drugs are traditionally studied using cancer cell lines and animal models. The thienodiazepine class of BET inhibitors, such as JQ1, has been extensively studied for the potential treatment of hematological malignancies and several small molecules belonging to this class are currently under clinical investigation. While these compounds are well known to inhibit cancer cell growth and cause apoptosis, their effects on stem cells, particularly mesenchymal stem cells (MSCs), which are important for regeneration of damaged cells and tissues, are unknown. In this study we employed umbilical cord derived MSCs as a model system to evaluate the safety of JQ1. METHODS: Cord derived MSCs were treated with various doses of JQ1 and subjected to cell metabolic activity, apoptosis, and cell cycle analyses using MTT assay, Annexin V/FITC and PI staining, and flow cytometry, respectively. The effect of JQ1 on gene expression was determined using microarray and quantitative real-time reverse transcriptase polymerase chain reaction analysis. Furthermore, protein expression of apoptotic and neuronal markers was carried out using western blot and immunostaining, respectively. RESULTS: Our results showed that JQ1 inhibited cell growth and caused cell cycle arrest in G1 phase but did not induce apoptosis or senescence. JQ1 also down-regulated genes involved in self-renewal, cell cycle, DNA replication, and mitosis, which may have negative implications on the regenerative potential of MSCs. In addition, JQ1 interfered with signaling pathways by down regulating the expression of WNT, resulting in limiting the self renewal. These results suggest that anticancer agents belonging to the thienodiazepine class of BET inhibitors should be carefully evaluated before their use in cancer therapy. CONCLUSIONS: This study revealed for the first time that JQ1 adversely affected MSCs, which are important for repair and regeneration. JQ1 specifically modulated signal transduction and inhibited growth as well as self-renewal. These findings suggest that perinatal MSCs could be used to supplement animal models for investigating the safety of anticancer agents and other drugs. PMID- 26830475 TI - DNA Distortion Caused by Uracil-Containing Intrastrand Cross-Links. AB - Four uracil-containing intrastrand cross-links have been detected in human cells upon UV irradiation of 5-bromouracil-containing DNA, namely 5'-G[8-5]U-3', 5'-U[5 8]G-3', 5'-A[8-5]U-3', and 5'-A[2-5]U-3'. These lesions feature unique composition and connectivity compared with other intrastrand cross-links reported in the literature. For the first time, structural information obtained using molecular dynamics (MD) simulations reveal that all four lesions distort the DNA helix, which can involve an extrahelical location of the cross-link, changes in the helical interactions of the complementary nucleotides, or disruption of hydrogen bonding in the flanking base pairs up to two positions from the cross linked site; however, the degree of distortion varies between the cross-links, being affected by the sequence, nucleobase-nucleobase connectivity, and the purine involved. Most importantly, the relative distortion of the damaged DNA provides the first structural explanation for the observed abundances of the four uracil-containing cross-links. Furthermore, the highly distorted conformations suggest that these lesions will likely have severe implications for DNA replication and repair processes in cells. PMID- 26830476 TI - The Roles of EP4 Prostanoid Receptors in Cancer Malignancy Signaling. AB - The lipid mediator prostanoids consist of prostaglandins and thromboxanes, and are synthesized from arachidonic acid by the action of cyclooxygenase. There are five major prostanoids, including prostaglandin E2 (PGE2), and they are involved in a variety of biological responses such as inflammation, allergy, parturition, and tumorigenesis. These prostanoids exert their effects via activation of their cognate G protein coupled receptors, e.g., E-type prostanoid (EP) receptors for PGE2. The EP receptors are composed of four subtypes, namely EP1 to EP4. Here, breakthroughs in the last dozen years of research are introduced, with a special focus on some important findings of EP4 receptor-mediated signaling and the signaling associated with cancer development, particularly in colon cancer. PMID- 26830477 TI - Plant Lysophosphatidic Acids: A Rich Source for Bioactive Lysophosphatidic Acids and Their Pharmacological Applications. AB - Lysophosphatidic acid (1-acyl-2-lyso-sn-glycero-3-phosphatidic acid; LPA) is a simple and minor phospholipid in plants. Plant LPAs are merely metabolic intermediates in de novo lipid synthesis in plant cell membranes or for glycerophospholipid storage. The production and metabolisms of LPAs in animals are also well characterized and LPAs have diverse cellular effects in animal systems; i.e., from brain development to wound healing through the activation of G protein-coupled LPA receptors. Recent studies show that various foodstuffs such as soybean, cabbage and seeds such as sesame and sunflower contain bioactive LPAs. Some LPAs are produced from phosphatidic acid during the digestion of foodstuff. In addition, herbal medicines such as corydalis tuber, and especially ginseng, contain large amounts of LPAs compared to foodstuffs. Herbal LPAs bind to cell surface LPA receptors in animal cells and exert their biological effects. Herbal LPAs elicit [Ca(2+)]i transient and are coupled to various Ca(2+) dependent ion channels and receptor regulations via the activation of LPA receptors. They also showed beneficial effects of in vitro wound healing, in vivo anti-gastric ulcer, anti-Alzheimer's disease, autotaxin inhibition and anti metastasis activity. Thus, herbal LPAs can be useful agents for human health. Humans can utilize exogenous plant-derived LPAs for preventive or therapeutic purposes if plant-derived LPAs are developed as functional foods or natural medicine targeting LPA receptors. This brief review article introduces the known rich sources of herbal LPAs and herbal LPA binding protein, describes their biological effects, and further addresses possible clinical applications. PMID- 26830478 TI - Intermolecular Interactions and the Release Pattern of Electrospun Curcumin Polyvinyl(pyrrolidone) Fiber. AB - An electrospun fiber of polyvinyl(pyrrolidone) (PVP)-Tween 20 (T20) with curcumin as the encapsulated drug has been developed. A study of intermolecular interactions was performed using Raman spectroscopy, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The Raman and FT-IR studies showed that curcumin preferrably interacted with T20 and altered PVP chain packing, as supported by XRD and physical stability data. The hydroxyl stretching band in PVP shifted to a lower wavenumber with higher intenstity in the presence of curcumin and PVP, indicating that hydrogen bond formation is more intense in a curcumin or curcumin-T20 containing fiber. The thermal pattern of the fiber did not indicate phase separation. The conversion of curcumin into an amorphous state was confirmed by XRD analysis. An in vitro release study in phosphate buffer pH 6.8 showed that intermolecular interactions between each material influenced the drug release rate. However, low porosity was found to limit the hydrogen bond-mediated release. PMID- 26830479 TI - Neuroprotective Effect of Ocular Hypotensive Drugs: Latanoprost/Timolol in Combination Are More Effective than Each as Monotherapy in RGC-5. AB - The combination of timolol and latanoprost, which are ocular hypotensive agents, has a greater ocular hypotensive effect than each as monotherapy. However, the protective effect of the combination is not well understood. In the present study, we investigated whether latanoprost/timolol in combination has an additive or synergistic cytoprotective effect on neuro retinal cells (RGC-5). To investigate the protective effects of timolol/latanoprost in combination, cultured RGC-5 were treated with various concentrations of these two agents, singly or together, after which the cells were exposed to oxidative stress, serum deprivation, or endoplasmic reticulum (ER) stress in vitro. Cells were also treated with an Akt inhibitor, LY294002, to examine the mechanism of the protective effect. Latanoprost, timolol, and the two in combination reduced cell death induced by oxidative stress, serum deprivation, or ER stress. The latanoprost/timolol combination reduced cell death to a greater extent than monotherapy with latanoprost or timolol on serum deprivation only, and LY294002 inhibited the protective effect of their combination. These findings suggest that timolol/latanoprost in combination have a protective effect against serum deprivation only by activation of Akt signaling. Furthermore, this combination has not only an ocular hypotensive effect but also a neuroprotective effect. PMID- 26830481 TI - Hepatic Tumor Metastases Cause Enhanced PEGylated Liposome Uptake by Kupffer Cells. AB - Kupffer cells in livers bearing tumor metastases were found to have promoted tumor invasion and exacerbated the metastasis. This implies that the function of Kupffer cells might differ between animals bearing hepatic metastases and those that are healthy. Kupffer cells are considered responsible for the accumulation of liposomes in the liver. In this study, we hypothesized that the alteration in the function of Kupffer cells by hepatic metastasis would also affect the biodistribution of liposomes following intravenous administration. The hepatic accumulation and the blood concentration of PEGylated liposomes were compared between healthy mice and tumor-bearing mice. We noted that hepatic accumulation and elimination from the blood were significantly accelerated in tumor-bearing mice, indicating that our hypothesis was correct. In the tumor-bearing mice, the proportion of Kupffer cells taking up liposomes was significantly increased. Intravenous injection of oxaliplatin (l-OHP) containing PEGylated liposomes decreased the fraction of Kupffer cells, but this administration caused no injury to the hepatocytes. These results suggest that PEGylated liposomes containing l OHP may have the potential to treat metastatic hepatic cancer-not only via the direct killing of the cancer cells but also via a reduction in tumor-supportive Kupffer cells. PMID- 26830480 TI - Effects of Glycated Whey Protein Concentrate on Pro-inflammatory Cytokine Expression and Phagocytic Activity in RAW264.7 Macrophages. AB - The aim of this study was to determine the stimulatory effects of Maillard reaction, a non-enzymatic browning reaction on the expression of pro-inflammatory cytokines and phagocytic activity induced by whey protein concentrate (WPC). Glycated WPC (G-WPC) was prepared by a reaction between WPC and the lactose it contained. The fluorescence intensity of G-WPC dramatically increased after one day, and high molecular weight complexes formed via the Maillard reaction were also observed in the sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles. G-WPC demonstrated immunomodulatory effects, including stimulation of increased nitric oxide production and cytokine expressions (i.e., tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-6), compared to WPC. Furthermore, the phagocytic activity of RAW264.7 cells was significantly increased upon treatment with G-WPC, compared to WPC. Therefore, we suggest that G-WPC can be utilized as an improved dietary source for providing immune modulating activity. PMID- 26830482 TI - Proteomic Profiling in the Spinal Cord and Sciatic Nerve in a Global Cerebral Ischemia-Induced Mechanical Allodynia Mouse Model. AB - Central post-stroke pain (CPSP) is one of the complications of cerebral ischemia and neuropathic pain syndrome. At present, there are few studies of pain in regions such as the spinal cord or sciatic nerve in cerebral ischemic animal models. To identify proteomic changes in the spinal cord and sciatic nerve in global cerebral ischemic model mice, in the present study we performed an investigation using proteomic methods. In a comparison between the intensity of protein spots obtained from a sham and that from a bilateral carotid artery occulusion (BCAO) in spinal cord and sciatic nerve, the levels of 10 (spinal cord) and 7 (sciatic nerve) protein spots were altered. The protein levels in the spinal cord were significantly increased in N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 (DDAH1), 6-phosphogluconolactonase isoform 1, and precursor apoprotein A-I and decreased in dihydropyrimidinase-related protein 2 (CRMP-2), enolase 1B, rab guanosine 5'-diphosphate (GDP) dissociation inhibitor beta, septin-2 isoform a, isocitrate dehydrogenase subunit alpha, cytosolic malate dehydrogenase, and adenosine triphosphate synthase. The protein levels in the sciatic nerve were significantly increased in a mimecan precursor, myosin light chain 1/3, and myosin regulatory light chain 2 (MLC2), and decreased in dihydropyrimidinase-related protein 3 (CRMP-4), protein disulfide-isomerase A3, 3 hydroxy-3-methylglutaryl-coenzyme A synthase 1, and B-type creatine kinase. In addition, CRMP-2 and CRMP-4 protein levels were decreased, and DDAH1 and MLC2 protein levels were increased on day 1 after BCAO using Western blotting. These results suggested that changes in these proteins may be involved in the regulation of CPSP. PMID- 26830483 TI - Design and Synthesis of New Phthalazinone Derivatives Containing Benzyl Moiety with Anticipated Antitumor Activity. AB - The acetohydrazide derivative reacted with carbon electrophiles such as acid chlorides, acetylacetone, ethyl acetoacetate and aromatic aldehydes to give some interesting heterocyclic compounds. The hydrazide derivative reacted with acetophenone which in turn underwent Vielsmeier-Haack reaction. Also, the phthalazinethione has been synthesized and its behavior towards hydrazine hydrate, oxidizing agent and ethyl chloroacetate has been investigated. The newly synthesized compounds were characterized by spectroscopic data. The antimicrobial, the cytotoxic, and the antioxidant activities of some of the synthesized products were evaluated. Some of the tested compounds showed very strong cytotoxic activity with respect to the standard. PMID- 26830484 TI - High Expression Levels of NADPH Oxidase 3 in the Cerebrum of Ten-Week-Old Stroke Prone Spontaneously Hypertensive Rats. AB - We previously demonstrated that the high levels of oxidative stress in the brains of ten-week-old stroke-prone hypertensive rats (SHRSP) were attributable to intrinsic, not extrinsic factors (Biol. Pharm. Bull., 33, 2010, Michihara et al.). The aim of the present study was to determine whether increases in the enzymes producing reactive oxygen species (ROS), reductions in the enzymes and proteins removing ROS, or increases in an enzyme and transporter removing antioxidants promoted oxidative stress in the SHRSP cerebrum. No significant decreases were observed in the mRNA levels of enzymes that remove ROS between SHRSP and normotensive Wistar Kyoto rats. The activity of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and the protein and mRNA levels of NOX3, an enzyme that produces ROS, were significantly increased in the SHRSP cerebrum. These results suggested that the high expression levels of NOX3 increased oxidative stress in the SHRSP cerebrum. PMID- 26830485 TI - Maackiapterocarpan B from Sophora tonkinensis Suppresses Inflammatory Mediators via Nuclear Factor-kappaB and Mitogen-Activated Protein Kinase Pathways. AB - Maackiapterocarpan B, one of the pterocarpan analogs found in Sophora tonkinensis, is known to display pharmacological activities. However, the anti inflammatory effects of maackiapterocarpan B and its molecular mechanism have yet to be clearly elucidated. In the present study, the effects of maackiapterocarpan B on macrophage-mediated inflammation in vitro were assessed. Maackiapterocarpan B inhibited the production of nitric oxide, the expression of tumor necrosis factor alpha, colony stimulating factor 2, interleukin-1beta and interleukin-6, and the activation of nuclear factor-kappaB and mitogen-activated protein kinases in lipopolysaccharide-stimulated macrophages. These observations suggest the potential of maackiapterocarpan B in the treatment of inflammatory diseases. PMID- 26830486 TI - Effect of N-Phenylanthranilic Acid Scaffold Nonsteroidal Anti-inflammatory Drugs on the Mitochondrial Permeability Transition. AB - Hepatotoxicity is a known side effect of nonsteroidal anti-inflammatory drugs (NSAIDs). In the present study, the effects of N-phenylanthranilic acid (NPA) scaffold NSAIDs on rat liver mitochondria were examined. Mefenamic acid (MEF, 200 uM) induced mitochondrial swelling, which was inorganic phosphate (Pi)-dependent and suppressed by cyclosporin A (CsA, 2.5 uM), similar to calcium-induced swelling. Mitochondrial swelling was also observed following the addition of 200 uM flufenamic acid (FLU), meclofenamic acid (MCL), and tolfenamic acid (TOL). Less swelling was observed with the addition of 200 uM diclofenac (DIC) or NPA. Diphenylamine (DPA)-induced swelling occurred in a Pi-independent manner and was not sensitive to CsA. The mechanism by which DPA interacted with the mitochondrial inner membrane differed from those of the other NPA scaffold NSAIDs. The addition of 50 uM MEF, MCL, TOL, and FLU had uncoupling effects in mitochondrial inner membrane. These NSAIDs dose-dependently obstructed electron transport in the respiratory chain. NSAIDs are known to have various dynamic structures, and the solvation free energies (dGWs: an index of stereo hydrophobicity) of the conformers obtained were determined using a molecular orbital analysis. The relationship between the dynamic structures and swelling induced by NPA scaffold NSAIDs was also examined. PMID- 26830487 TI - Eculizumab Dosing Intervals Longer than 17 Days May Be Associated with Greater Risk of Breakthrough Hemolysis in Patients with Paroxysmal Nocturnal Hemoglobinuria. AB - Eculizumab given bi-weekly is widely recommended for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). We undertook a retrospective analysis on the medical records of 763 dosings of 14 PNH patients to investigate whether a threshold would exist in dosing intervals associated with breakthrough hemolysis. We identified 12 events of breakthrough hemolysis in 4 patients. Multivariate logistic regression and receiver operating characteristics (ROC) analysis revealed a significant association between increased risk of breakthrough hemolysis and prolonged dosing intervals of 17 days or more and concomitant inflammation: odds ratios (OR) and 95% confidence intervals (CIs) were 1.6 (1.3 2.0, p<0.01) and 5.5 (1.3-22.8, p=0.02), respectively. ROC analysis showed that the best cut-off dosing interval discriminating breakthrough hemolysis was 16.5 days. We consider that eculizumab dosing intervals longer than 17 days may be associated with an increased risk for developing breakthrough hemolysis in patients with PNH. PMID- 26830488 TI - Kamikihito Ameliorates Lipopolysaccharide-Induced Sickness Behavior via Attenuating Neural Activation, but Not Inflammation, in the Hypothalamic Paraventricular Nucleus and Central Nucleus of the Amygdala in Mice. AB - Sickness behavior is a series of behavioral and psychological changes that develop in those stricken with cancers and inflammatory diseases. The etiological mechanism of sickness behavior is not known in detail, and consequently there are no established standard therapies. Kamikihito (KKT), a Kampo (traditional Japanese herbal) medicine composed of 14 herbs, has been used clinically to treat psychiatric dysfunction. Previously, we found that KKT ameliorated sickness behavior in mice inoculated with murine colon 26 adenocarcinoma cells. In this study, we examined the effects of KKT on bacterial endotoxin lipopolysaccharide (LPS)-induced sickness behavior in mice. The administration of LPS caused the emotional aspects of sickness behavior, such as loss of object exploration, social interaction deficit, and depressive-like behavior. LPS also induced mRNA expression for cyclooxygenase (COX)-2, interleukin (IL)-1beta and IL-6, and increased the number of c-Fos immunopositive cells in the hypothalamus and amygdala. KKT ameliorated the behavioral changes and reversed the increases in c Fos immunopositive cells in the two brain regions, but did not influence the mRNA expression. These results suggest that KKT ameliorates sickness behavior via the suppression of neural activation without anti-inflammatory effects, and that KKT has the potential to treat sickness behavior. PMID- 26830489 TI - Clinical Evaluation of Pharmacist Interventions in Patients Treated with Anti methicillin-Resistant Staphylococcus aureus Agents in a Hematological Ward. AB - The therapeutic effects of anti-methicillin-resistant Staphylococcus aureus (MRSA) agents, vancomycin (VCM), teicoplanin (TEIC), and arbekacin (ABK), depend on their concentrations in blood. Therefore, therapeutic drug monitoring (TDM) is important when these antibiotics are used. In the hematological ward at Tokushima University Hospital, pharmacists have ordered the measurement of blood VCM, TEIC, and ABK concentrations to promote the use of TDM in accordance with an agreed protocol since 2013. Moreover, the infection control team includes several medical disciplines and has advised on the optimal treatment using VCM, TEIC, and ABK since 2013. This study aimed to investigate the clinical effectiveness of these pharmacist interventions. We retrospectively studied 145 cases in which patients were treated with VCM, TEIC, or ABK between January 2012 and December 2013 in the hematological ward at Tokushima University Hospital. The patients were divided into a control group (71 cases) and an intervention group (74 cases), and their clinical outcomes were compared. The rate of achievement of effective drug concentrations significantly increased in the intervention group (74%), compared to the rate in the control group (55%). Moreover, univariate and multivariate Cox proportional hazard regression revealed that pharmacist intervention and appropriate concentrations of anti-MRSA agents were independent factors associated with reduced hospitalization periods in patients with lymphoma. Our study revealed that proactive pharmacist intervention may improve the therapeutic effect of anti-MRSA agents in hematology ward patients. PMID- 26830490 TI - A New Method to Assess Asymmetry in Fingerprints Could Be Used as an Early Indicator of Type 2 Diabetes Mellitus. AB - BACKGROUND: Inexpensive screening tools are needed to identify individuals predisposed to developing diabetes mellitus (DM). Such early identification coupled with an effective intervention could help many people avoid the substantial health costs of this disease. We investigated the hypothesis that fluctuating asymmetry (FA) in fingerprints is an indicator of type 2 diabetes mellitus (T2DM). METHODS: Participants with T2DM, with T1DM, and without any indication or known family history of diabetes were fingerprinted with a Crossmatch Verifier 320 LC scanner. Asymmetry scores for each finger pair were assessed using both pattern analysis (ridge counts), and a wavelet-based analysis. RESULTS: Both methods for scoring asymmetry predicted risk of T2DM for finger pair IV, controlling for gender and age. AUC scores were significantly greater than the null for pattern asymmetry scores (finger IV AUC = 0.74), and wavelet asymmetry scores for finger pair IV (AUC = 0.73) and finger pair V (AUC = 0.73), for predicting T2DM. In addition, wavelet asymmetry scores for finger pair IV (AUC = 0.80) and finger pair V (AUC = 0.85) significantly predicted risk of T1DM. CONCLUSIONS: A diagnostic tool based on FA in the fingerprints of finger pair IV, measured using a wavelet analysis could be developed for predicting risk prior to associated health problems for both T2DM and T1DM. In addition, given that that the prints for fingers IV and V develop during the 14-17 weeks of gestation, we predict that interventions during this time period of pregnancy will be most successful. PMID- 26830491 TI - Retinal Imaging Techniques for Diabetic Retinopathy Screening. AB - Due to the increasing prevalence of diabetes mellitus, demand for diabetic retinopathy (DR) screening platforms is steeply increasing. Early detection and treatment of DR are key public health interventions that can greatly reduce the likelihood of vision loss. Current DR screening programs typically employ retinal fundus photography, which relies on skilled readers for manual DR assessment. However, this is labor-intensive and suffers from inconsistency across sites. Hence, there has been a recent proliferation of automated retinal image analysis software that may potentially alleviate this burden cost-effectively. Furthermore, current screening programs based on 2-dimensional fundus photography do not effectively screen for diabetic macular edema (DME). Optical coherence tomography is becoming increasingly recognized as the reference standard for DME assessment and can potentially provide a cost-effective solution for improving DME detection in large-scale DR screening programs. Current screening techniques are also unable to image the peripheral retina and require pharmacological pupil dilation; ultra-widefield imaging and confocal scanning laser ophthalmoscopy, which address these drawbacks, possess great potential. In this review, we summarize the current DR screening methods using various retinal imaging techniques, and also outline future possibilities. Advances in retinal imaging techniques can potentially transform the management of patients with diabetes, providing savings in health care costs and resources. PMID- 26830493 TI - Concerns about covert HIV testing are associated with delayed presentation in Ethiopian adults with suspected malaria: a cross-sectional study. AB - BACKGROUND: Although early diagnosis and prompt treatment is important in preventing mortality from malaria, presentation of symptomatic individuals is often relatively late. One possible contributing factor is that fear of covert human immunodeficiency virus (HIV) testing delays presentation in adults. We aimed to survey the magnitude of such concerns and their association with delayed presentation with suspected malaria. METHODS: The study design was a health facility-based cross-sectional survey. The study population consisted of adults with suspected malaria who presented to health centres in central Ethiopia. Data were collected on attitudes to HIV testing and the duration between onset of symptoms and treatment seeking for suspected malaria. RESULTS: Eight hundred and ten individuals provided data. Of these, 406 (50 %) perceived that HIV testing was routinely done on blood donated for malaria diagnosis, and 327 (40 %) considered that community members delayed seeking medical advice because of these concerns. Concerns about HIV testing were associated with delays in attending for malaria diagnosis and treatment, with 117 individuals (29 %) of those with concerns about covert HIV testing waiting for 4 days or more, compared to 89 (22 %) of those who did not have any such concerns (p = 0.03). One hundred and twenty nine (16 %) individuals stated that concern about HIV testing was the main reason for the delay in seeking treatment, and 46 % of these individuals presented after experiencing symptoms of malaria infection for three days or more compared to 22 % of the 681 individuals who had no such concerns (p < 0.001). Analysis stratified by health centre demonstrated that these associations were a consequence of Meki health centre (odds ratio for duration of symptoms greater than 3 days if patient has concerns about HIV testing was 8.72; 95 % confidence intervals 3.63 to 20.97). CONCLUSIONS: In adults living in central Ethiopia, the perception that HIV testing accompanied the investigation of suspected malaria was common. This is likely to impede presentation for early medical treatment in some areas and represents a reversible risk factor that deserves further study. PMID- 26830494 TI - Genomic and proteomic evidence supporting the division of the plant pathogen Ralstonia solanacearum into three species. AB - BACKGROUND: The increased availability of genome sequences has advanced the development of genomic distance methods to describe bacterial diversity. Results of these fast-evolving methods are highly correlated with those of the historically standard DNA-DNA hybridization technique. However, these genomic based methods can be done more rapidly and less expensively and are less prone to technical and human error. They are thus a technically accessible replacement for species delineation. Here, we use several genomic comparison methods, supported by our own proteomic analyses and metabolic characterization as well as previously published DNA-DNA hybridization analyses, to differentiate members of the Ralstonia solanacearum species complex into three species. This pathogen group consists of diverse and widespread strains that cause bacterial wilt disease on many different plants. RESULTS: We used three different methods to compare the complete genomes of 29 strains from the R. solanacearum species complex. In parallel we profiled the proteomes of 73 strains using Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). Proteomic profiles together with genomic sequence comparisons consistently and comprehensively described the diversity of the R. solanacearum species complex. In addition, genome-driven functional phenotypic assays excitingly supported an old hypothesis (Hayward et al. (J Appl Bacteriol 69:269-80, 1990)), that closely related members of the R. solanacearum could be identified through a simple assay of anaerobic nitrate metabolism. This assay allowed us to clearly and easily differentiate phylotype II and IV strains from phylotype I and III strains. Further, genomic dissection of the pathway distinguished between proposed subspecies within the current phylotype IV. The assay revealed large scale differences in energy production within the R. solanacearum species complex, indicating coarse evolutionary distance and further supporting a repartitioning of this group into separate species. CONCLUSIONS: Together, the results of these studies support the proposed division of the R. solanacearum species complex into three species, consistent with recent literature, and demonstrate the utility of proteomic and genomic approaches to delineate bacterial species. PMID- 26830492 TI - The Evolution of Teleophthalmology Programs in the United Kingdom: Beyond Diabetic Retinopathy Screening. AB - Modern ophthalmic practice in the United Kingdom is faced by the challenges of an aging population, increasing prevalence of systemic pathologies with ophthalmic manifestations, and emergent treatments that are revolutionary but dependent on timely monitoring and diagnosis. This represents a huge strain not only on diagnostic services but also outpatient management and surveillance capacity. There is an urgent need for newer means of managing this surge in demand and the socioeconomic burden it places on the health care system. Concurrently, there have been exponential increases in computing power, expansions in the strength and ubiquity of communications technologies, and developments in imaging capabilities. Advances in imaging have been not only in terms of resolution, but also in terms of anatomical coverage, allowing new inferences to be made. In spite of this, image analysis techniques are still currently superseded by expert ophthalmologist interpretation. Teleophthalmology is therefore currently perfectly placed to face this urgent and immediate challenge of provision of optimal and expert care to remote and multiple patients over widespread geographical areas. This article reviews teleophthalmology programs currently deployed in the United Kingdom, focusing on diabetic eye care but also discussing glaucoma, emergency eye care, and other retinal diseases. We examined current programs and levels of evidence for their utility, and explored the relationships between screening, teleophthalmology, disease detection, and monitoring before discussing aspects of health economics pertinent to diabetic eye care. The use of teleophthalmology presents an immense opportunity to manage the steadily increasing demand for eye care, but challenges remain in the delivery of practical, viable, and clinically proven solutions. PMID- 26830495 TI - Complete clinical course of envenomation by Protobothrops mangshanensis: delayed coagulopathy and response to Trimeresurus albolabris antivenom. AB - INTRODUCTION: Protobothrops mangshanensis, the Mangshan pit viper, is a rare pit viper native to the area surrounding Mount Mang in China's Hunan province. Toxicity from envenomation is not well characterized. CASE DETAILS: A 33-year-old male presented to an emergency department (ED) after being bitten on the forearm by his P. mangshanensis. He complained of mild swelling and pain at the bite site. He was admitted for observation and toxicology consultation. Following initially normal coagulation studies including platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer, fibrinogen decreased to 121 mg/dL and D-dimer concurrently rose to 377 ng/mL over 24 h. On hospital day 2 fibrinogen stabilized at 109 mg/dL and he was discharged with outpatient laboratory monitoring. Three days later, he returned with bruising to the contralateral arm. Fibrinogen was undetectable (<40 mg/dL) and PT was 14.6 s. He declined admission but returned 2 d later with bruising to the nose. Bloodwork revealed immeasurably prolonged PT, aPTT, and thrombin time, but he eloped. Late that evening he returned and was treated with three vials of Green pit viper (Trimeresurus albolabris) antivenom. Within 24 h coagulopathy improved markedly; at five days, coagulation abnormalities resolved. DISCUSSION: Mangshan pit viper envenomations may cause isolated hemotoxicity, despite molecular studies suggesting additional neurotoxicity and myotoxicity. T. albolabris antivenom appears effective in treating the resultant coagulopathy. CONCLUSION: We report the natural history of envenomation by the Mangshan pit viper. A delayed coagulopathy, apparently fibrinolytic in nature, is unaccompanied by local tissue destruction and responsive to Green pit viper antivenom. PMID- 26830496 TI - Optimal methods for fitting probability distributions to propagule retention time in studies of zoochorous dispersal. AB - BACKGROUND: Propagule retention time is a key factor in determining propagule dispersal distance and the shape of "seed shadows". Propagules dispersed by animal vectors are either ingested and retained in the gut until defecation or attached externally to the body until detachment. Retention time is a continuous variable, but it is commonly measured at discrete time points, according to pre established sampling time-intervals. Although parametric continuous distributions have been widely fitted to these interval-censored data, the performance of different fitting methods has not been evaluated. To investigate the performance of five different fitting methods, we fitted parametric probability distributions to typical discretized retention-time data with known distribution using as data points either the lower, mid or upper bounds of sampling intervals, as well as the cumulative distribution of observed values (using either maximum likelihood or non-linear least squares for parameter estimation); then compared the estimated and original distributions to assess the accuracy of each method. We also assessed the robustness of these methods to variations in the sampling procedure (sample size and length of sampling time-intervals). RESULTS: Fittings to the cumulative distribution performed better for all types of parametric distributions (lognormal, gamma and Weibull distributions) and were more robust to variations in sample size and sampling time-intervals. These estimated distributions had negligible deviations of up to 0.045 in cumulative probability of retention times (according to the Kolmogorov-Smirnov statistic) in relation to original distributions from which propagule retention time was simulated, supporting the overall accuracy of this fitting method. In contrast, fitting the sampling-interval bounds resulted in greater deviations that ranged from 0.058 to 0.273 in cumulative probability of retention times, which may introduce considerable biases in parameter estimates. CONCLUSIONS: We recommend the use of cumulative probability to fit parametric probability distributions to propagule retention time, specifically using maximum likelihood for parameter estimation. Furthermore, the experimental design for an optimal characterization of unimodal propagule retention time should contemplate at least 500 recovered propagules and sampling time-intervals not larger than the time peak of propagule retrieval, except in the tail of the distribution where broader sampling time-intervals may also produce accurate fits. PMID- 26830498 TI - Associations between CD36 gene polymorphisms and metabolic response to a short term endurance-training program in a young-adult population. AB - Recent studies have shown that CD36 gene variants are associated with an increased prevalence of chronic disease. Although a genetic component to trainability has been proven, no data are available specifically on the influence of CD36 on training response. Two single nucleotide polymorphisms (SNPs) (rs1527479 and rs1984112) were assessed for associations with whole-body substrate oxidation, response to a 75-g dextrose oral glucose tolerance test, fasting plasma lipids, and cardiovascular disease risk factors in a young healthy cohort, both using cross-sectional analysis and following a 4-week endurance exercise training program. Genotyping was performed using real-time polymerase chain reaction. Cross-sectional data were collected in 34 individuals (age, 22.7 +/- 3.5 years), with 17 completing the training program. At baseline, TT SNP carriers at rs1527479 and wild-type GG carriers at rs1984112 were associated with significantly greater whole-body rate of fat oxidation (Fatox) during submaximal exercise (P < 0.05), whilst AA carriers at the same position were associated with elevated triglyceride (TG) levels. A significant genotype * time interaction in Fatox at SNP rs1984112 was identified at rest. Significant genotype * time interactions were present at rs1527479, with TT carriers exhibiting a favourable response to training when compared with C-allele carriers for fasting TG, diastolic blood pressure (DBP), and mean arterial pressure (MAP). In conclusion, cross-sectional assessment identified associations with Fatox and TG. Training response at both SNPs identified "at-risk" genotypes responding favourably to the training stimulus in Fatox, TG, DBP, and MAP. Although these data show potential pleiotropic influence of CD36 SNPs, assessment in a larger cohort is warranted. PMID- 26830497 TI - A multiplex immunoassay for the non-invasive detection of bladder cancer. AB - BACKGROUND: Urine based assays that can non-invasively detect bladder cancer (BCa) have the potential to reduce unnecessary and invasive procedures. The purpose of this study was to develop a multiplex immunoassay that can accurately and simultaneously monitor ten diagnostic urinary protein biomarkers for application as a non-invasive test for BCa detection. METHODS: A custom electrochemiluminescent multiplex assay was constructed (Meso Scale Diagnostics, LLC, Rockville, MD, USA) to detect the following urinary proteins; IL8, MMP9, MMP10, ANG, APOE, SDC1, A1AT, PAI1, CA9 and VEGFA. Voided urine samples from two cohorts were collected prior to cystoscopy and samples were analyzed blinded to the clinical status of the participants. Means (+/-SD) and receiver operating characteristic (ROC) curve analysis were used to compare assay performance and to assess the diagnostic accuracy of the diagnostic signature. RESULTS: Comparative diagnostic performance analyses revealed an AUROC value of 0.9258 for the multiplex assay and 0.9467 for the combination of the single-target ELISA assays (p = 0.625), so there was no loss of diagnostic utility for the MSD multiplex assay. Analysis of the independent 200-sample cohort using the multiplex assay achieved an overall diagnostic sensitivity of 0.85, specificity of 0.81, positive predictive value 0.82 and negative predictive value 0.84. CONCLUSIONS: It is technically feasible to simultaneously monitor complex urinary diagnostic signatures in a single assay without loss of performance. The described protein based assay has the potential to be developed for the non-invasive detection of BCa. PMID- 26830499 TI - Flavor Identification and Intensity: Effects of Stimulus Context. AB - Two experiments presented oral mixtures containing different proportions of the gustatory flavorant sucrose and an olfactory flavorant, either citral (Experiment 1) or lemon (Experiment 2). In 4 different sessions of each experiment, subjects identified each mixture as "mostly sugar" or "mostly citrus/lemon" or rated the perceived intensities of the sweet and citrus components. Different sessions also presented the mixtures in different contexts, with mixtures containing relatively high concentrations of sucrose or citral/lemon presented more often (skew sucrose or skew citral/lemon). As expected, in both experiments, varying stimulus context affected both identification and perceived intensity: Skewing to sucrose versus citral/lemon decreased the probability of identifying the stimuli as "mostly sugar" and reduced the ratings of sweet intensity relative to citrus intensity. Across both contextual conditions of both experiments, flavor identification associated closely with the ratio of the perceived sweet and citrus intensities. The results accord with a model, extrapolated from signal-detection theory, in which sensory events are represented as multisensory-multidimensional distributions in perceptual space. Changing stimulus context can shift the locations of the distributions relative to response criteria, Decision rules guide judgments based on both sensory events and criteria, these rules not necessarily being identical in tasks of identification and intensity rating. PMID- 26830501 TI - Sixty Minutes of Physical Activity per Day Included Within Preschool Academic Lessons Improves Early Literacy. AB - BACKGROUND: The effects of increases in physical activity (PA) on early literacy skills in preschool children are not known. METHODS: Fifty-four African-American preschool children from a low socioeconomic urban Head Start participated over 8 months. A 2-group, quasi-experimental design was used with one preschool site participating in the PA intervention and a second site participating as the control site. The PA program was designed to promote 300 minutes/week of moderate to vigorous PA academic lessons. Academic achievement related to early literacy and phonological awareness in the areas of rhyming and alliteration were assessed at baseline, 4 and 8 months. RESULTS: Over 8 months, rhyming significantly (p < .01) improved in the PA group (173 +/- 12%) compared with the controls (28 +/- 8%) resulting in between group differences at 8 months (p < .01). Alliteration significantly (p < .01) improved in the PA group (52 +/- 16%) compared with controls (13 +/- 5%), resulting in between group differences at 8 months (p < .01). As minutes of exposure to moderate to vigorous PA increased, the change in picture naming (R(2) = .35, p < .05), alliteration (R(2) = .38, p < .05), and rhyming (R(2) = .42, p < .05), increased. CONCLUSION: A teacher-directed PA program is effective at increasing PA and improving early literacy. PMID- 26830500 TI - Physiologically Low Oxygen Enhances Biomolecule Production and Stemness of Mesenchymal Stem Cell Spheroids. AB - Multicellular human mesenchymal stem cell (hMSC) spheroids have been demonstrated to be valuable in a variety of applications, including cartilage regeneration, wound healing, and neoangiogenesis. Physiological relevant low oxygen culture can significantly improve in vitro hMSC expansion by preventing cell differentiation. We hypothesize that hypoxia-cultured hMSC spheroids can better maintain the regenerative properties of hMSCs. In this study, hMSC spheroids were fabricated using hanging drop method and cultured under 2% O2 and 20% O2 for up to 96 h. Spheroid diameter and viability were examined, as well as extracellular matrix (ECM) components and growth factor levels between the two oxygen tensions at different time points. Stemness was measured among the spheroid culture conditions and compared to two-dimensional cell cultures. Spheroid viability and structural integrity were studied using different needle gauges to ensure no damage would occur when implemented in vivo. Spheroid attachment and integration within a tissue substitute were also demonstrated. The results showed that a three-dimensional hMSC spheroid cultured at low oxygen conditions can enhance the production of ECM proteins and growth factors, while maintaining the spheroids' stemness and ability to be injected, attached, and potentially be integrated within a tissue. PMID- 26830502 TI - The Relationship Among School Safety, School Liking, and Students' Self-Esteem: Based on a Multilevel Mediation Model. AB - BACKGROUND: Perceptions of school safety have an important effect on students' development. Based on the model of "context-process-outcomes," we examined school safety as a context variable to explore how school safety at the school level affected students' self-esteem. METHODS: We used hierarchical linear modeling to examine the link between school safety at the school level and students' self esteem, including school liking as a mediator. The data were from the National Children's Study of China (NCSC), in which 6618 fourth- to fifth-grade students in 79 schools were recruited from 100 counties in 31 provinces in China. RESULTS: Multilevel mediation analyses showed that the positive relationship between school safety at the school level and self-esteem was partially mediated by school liking, controlling for demographics at both student and school levels. Furthermore, a sex difference existed in the multilevel mediation model. For boys, school liking fully mediated the relationship between school safety at the school level and self-esteem. However, school liking partially mediated the relationship between school safety at the school level and self-esteem among girls. CONCLUSION: School safety should receive increasing attention from policymakers because of its impact on students' self-esteem. PMID- 26830503 TI - Class Average Score for Teacher Support and Relief of Depression in Adolescents: A Population Study in Japan. AB - BACKGROUND: Factors contributing to the relief of depression among adolescents have not been sufficiently revealed. The aim of this study was to assess the effect of teacher support on depression in adolescent students. METHODS: We conducted a self-rating questionnaire survey among 2862 junior high school students and 93 homeroom teachers in Japan. We employed binary logistic regression models, with teacher support averaged for each class as an explanatory variable and depression as an objective variable. To examine the interaction terms of class average score for teacher support by economic status, by student sex, and by grade satisfaction were estimated. RESULTS: Higher class average scores for teacher support were independently associated with lower levels of depression among adolescents (odds ratio [OR], 0.739; 95% confidence interval [CI], 0.575-0.948). Furthermore, the interaction of class average scores for teacher support with grade satisfaction was significant (p = .025). The interaction of class average score for teacher support with economic status and with student sex was not significant. CONCLUSIONS: Our findings suggest that higher class average scores for teacher support were significantly associated with lower depression. These results can help homeroom teachers enhance interventions and promote the health of their homeroom students. PMID- 26830504 TI - Rebound Body Mass Index Growth in Year-Round Elementary Education Students of Largely Hispanic Descent Undergoing Obesity Interventions. AB - BACKGROUND: Body mass index (BMI) increases when students are away on summer vacation. Evaluation of serial BMI measurements on year-round students allows new insight into the reasons children gain weight seasonally. METHODS: The 206 first and second graders of 2-year-round elementary schools with obesity intervention programs were weighed and measured every 6 months from April 2011 until April 2013. BMI and BMI percentiles were recorded. RESULTS: Children <50th, 50th to 85th, and 85th to 95th BMI percentiles showed significant accelerated winter gains in BMI (p = 2.6 * 10(-7), p = 6.8 * 10(-10), and p = .0007, respectively) compared with the previous summers. Accelerated BMI growth of the second summer was absent when compared with the previous winter BMI changes in children <95th percentile (p = .48, p = .81, and p = .93). For children >95th percentile, BMI gain continued without significant changes year-round. CONCLUSIONS: School-wide interventions to induce BMI growth limitations are associated with significant rebound BMI gain with possible wintertime augmentation in nonobese children of year-round education programs. Obese children do not display rebound BMI gain, BMI seasonal change, or BMI limitations in response to school-based interventions. School weight control programs should consider off-campus sources of weight gain and be vigilant for rebound and delayed seasonal BMI gains. PMID- 26830505 TI - Barriers, Benefits, and Behaviors Related to Breakfast Consumption Among Rural Adolescents. AB - BACKGROUND: We sought to determine if perceived barriers, benefits, and modifiable behaviors support or interfere with breakfast consumption in a racially and economically diverse rural high school population. METHODS: The participants were 832 Minnesota adolescents from 16 rural high schools. We used baseline data from a group randomized trial aimed at increasing school breakfast participation through policy and environmental-level school changes. Students completed an online survey asking about demographics, breakfast eating behaviors, and the barriers and benefits of eating as it relates to school performance. Bivariate and multivariate logistic regression, accounting for clustering by school, was performed using SAS. Each scale was modeled independently. RESULTS: Participants were 9th and 10th grade students, 36% free/reduced-price lunch (FRL), 30% non-White, and 55% female. Breakfast skippers compared to nonbreakfast skippers reported fewer school related benefits and beliefs and more barriers to eating breakfast (p < .01). Adjusted models revealed students reported more positive beliefs (OR = 0.78, 95% CI = 0.73-0.83), more benefits (OR = 0.95, 95% CI = 0.93-0.97) and fewer barriers (OR = 0.85, 95% CI = 0.82-0.87) and were less likely to skip breakfast. CONCLUSIONS: Future intervention research should focus on alleviating barriers and enhancing education around the school related benefits of eating breakfast. PMID- 26830506 TI - Emotional Arousal and Regulation: Further Evidence of the Validity of the "How I Feel" Questionnaire for Use With School-Age Children. AB - BACKGROUND: The ability to understand and manage emotional experience is critical to children's health. This study confirmed the validity of the How I Feel (HIF) Questionnaire, a measure of children's emotional arousal and regulation, exploring its associations with measures of emotional and social functioning. METHODS: The sample was comprised of 1379 Italian students (aged 8 to 12 years) who attended schools interested in the study aims. Participants completed the 30 item HIF scale, and measures of emotional self-efficacy and social desirability (SD). Factor structures were assessed using confirmatory factor analysis. Invariance by age and gender, internal consistency, temporal stability, and concurrent validity were also tested. RESULTS: A 3-factor model was identified: frequency and intensity of (1) positive emotion--PE (8 items, alpha = .82), (2) negative emotion--NE (12 items, alpha = .86), and (3) positive and negative emotion control--EC (10 items, alpha = .77). This factor structure was invariant across age and gender groups. The HIF displayed moderate longitudinal stability over a 15-month period and a low social desirability effect. Positive emotion was positively associated with social acceptance and visibility, and negatively with social withdrawal. CONCLUSIONS: The HIF is a reliable and valid measure for research and school intervention promoting students' emotional and mental health. PMID- 26830507 TI - A School-Level Proxy Measure for Individual-Level Poverty Using School-Level Eligibility for Free and Reduced-Price Meals. AB - BACKGROUND: Socioeconomic status (SES) impacts health outcomes. The Youth Risk Behavior Survey (YRBS), like many school-based data sources, lacks individual level poverty information. We propose using school-level percentages of student eligibility for free/reduced-price meals (%FRPM) as a proxy for individual-level poverty. METHODS: Using the New York City (NYC) 2009 YRBS, we created school level poverty quartiles to append to individual YRBS records by ranking schools by %FRPM. We compared this with 2 other school-level poverty measures using students' home and school neighborhood-level poverty and measured the association of these 3 school-level proxies with individual's household income. Last, we evaluated health outcomes by race/ethnicity and poverty to demonstrate the importance of accounting for poverty. RESULTS: The school-level measure that used %FRPM had the strongest association with household income. When the school-level individual poverty proxy was included in illustrative analyses using YRBS data, patterns by poverty within race/ethnicity emerged that were not seen when looking at race/ethnicity alone. CONCLUSIONS: Using a poverty measure to analyze school based data will provide a better understanding of the impact of SES on health outcomes. Based on our evaluation, when individual-level information is not available, we propose using school-level %FRPM, which are publicly available throughout the United States. PMID- 26830508 TI - Biological and Sociocultural Factors During the School Years Predicting Women's Lifetime Educational Attainment. AB - BACKGROUND: Lifetime educational attainment is an important predictor of health and well-being for women in the United States. In this study, we examine the roles of sociocultural factors in youth and an understudied biological life event, pubertal timing, in predicting women's lifetime educational attainment. METHODS: Using data from the National Longitudinal Survey of Youth 1997 cohort (N = 3889), we conducted sequential multivariate linear regression analyses to investigate the influences of macro-level and family-level sociocultural contextual factors in youth (region of country, urbanicity, race/ethnicity, year of birth, household composition, mother's education, and mother's age at first birth) and early menarche, a marker of early pubertal development, on women's educational attainment after age 24. RESULTS: Pubertal timing and all sociocultural factors in youth, other than year of birth, predicted women's lifetime educational attainment in bivariate models. Family factors had the strongest associations. When family factors were added to multivariate models, geographic region in youth, and pubertal timing were no longer significant. CONCLUSION: Our findings provide additional evidence that family factors should be considered when developing comprehensive and inclusive interventions in childhood and adolescence to promote lifetime educational attainment among girls. PMID- 26830509 TI - Applying the Social Ecological Model to Creating Asthma-Friendly Schools in Louisiana. AB - BACKGROUND: In 2010, the Louisiana Asthma Management and Prevention Program (LAMP) implemented the Asthma-Friendly Schools Initiative in high-risk Louisiana populations. The social ecological model (SEM) was used as a framework for an asthma program implemented in 70 state K-12 public schools over 2 years. METHODS: Activities included a needs assessment, identification of students with asthma, individualized asthma action plans (AAP), staff trainings, environmental quality improvement, and school system policy changes to address the asthma burden. RESULTS: There were 522 new or existing asthma cases recognized. Asthma knowledge/awareness was measurably improved among school personnel. School indoor air quality was improved across all locations. School-level policies were adopted that improved AAP collection, compliance to bus-idling restrictions, and asthma medication self-carry. CONCLUSIONS: The SEM framework can be used for school based programs to address successfully and improve asthma-related issues from the individual through policy levels. PMID- 26830510 TI - Evidence for interspecific interactions in the ectoparasite infracommunity of a wild mammal. AB - BACKGROUND: Co-infection with multiple parasite species is commonly observed in nature and interspecific interactions are likely to occur in parasite infracommunities. Such interactions may affect the distribution of parasites among hosts but also the response of infracommunities to perturbations. However, the response of infracommunities to perturbations has not been well studied experimentally for ectoparasite communities of small mammal hosts. METHODS: In the current study we used experimental perturbations of the ectoparasite infracommunity of sengis from Africa. We suppressed tick recruitment by applying an acaride and monitored the effects on the ectoparasite community. RESULTS: Our treatment affected the target as well as two non-target species directly. The experimental removal of the dominant tick (Rhipicephalus spp.) resulted in increases in the abundance of chiggers and lice. However, while these effects were short-lived in chiggers, which are questing from the environment, they were long-lasting for lice which spend their entire life-cycle on the host. In addition, the recruitment rates of some ectoparasite species were high and did not always correspond to total burdens observed. CONCLUSION: These findings indicate that infracommunity interactions may contribute to patterns of parasite burdens. The divergent responses of species with differing life-history traits suggest that perturbation responses may be affected by parasite life-history and that the ectoparasite infracommunity of sengis may lack resilience to perturbations. The latter observation contrasts with the high resilience reported previously for endoparasite communities and also suggests that anti-parasite treatments can affect the distribution of non-target species. PMID- 26830511 TI - Transfers to hospital in planned home birth in four Nordic countries - a prospective cohort study. AB - INTRODUCTION: Women planning a home birth are transferred to hospital in case of complications or elevated risk for adverse outcomes. The aim of the present study was to describe the indications for transfer to hospital in planned home births, and the proportion of cases in which this occurs. MATERIAL AND METHODS: Women in Norway, Sweden, Denmark and Iceland who had opted for, and were accepted for, home birth at the onset of labor, were included in the study. Data from 3068 women, 572 nulliparas and 2446 multiparas, were analyzed for proportion of transfers during labor and within 72 h after birth, indications for transfer, how long before or after birth the transfer started, time from birth to start of transfer, duration and mode of transfer, and whether the transfer was classified as potentially urgent. Analyses were stratified for nulliparity and multiparity. RESULTS: One-third (186/572) of the nulliparas were transferred to hospital, 137 (24.0%) during labor and 49 (8.6%) after the birth. Of the multiparas, 195/2446 (8.0%) were transferred, 118 (4.8%) during labor and 77 (3.2%) after birth. The most common indication for transfers during labor was slow progress. In transfers after birth, postpartum hemorrhage, tears and neonatal respiratory problems were the most common indications. A total of 116 of the 3068 women had transfers classified as potentially urgent. CONCLUSIONS: One-third of all nulliparous and 8.0% of multiparous women were transferred during labor or within 72 h of the birth. The proportion of potentially urgent transfers was 3.8%. PMID- 26830512 TI - Production of Dopamine by Aromatic l-Amino Acid Decarboxylase Cells after Spinal Cord Injury. AB - Aromatic l-amino acid decarboxylase (AADC) cells are widely distributed in the spinal cord, and their functions are largely unknown. We have previously found that AADC cells in the spinal cord could increase their ability to produce serotonin (5-hydroxytryptamine) from 5-hydroxytryptophan after spinal cord injury (SCI). Because AADC is a common enzyme catalyzing 5-hydroxytryptophan to serotonin and l-3,4-dihydroxyphenylalanine (l-dopa) to dopamine (DA), it seems likely that the ability of AADC cells using l-dopa to synthesize DA is also increased. To prove whether or not this is the case, a similar rat sacral SCI model and a similar experimental paradigm were adopted as that which we had used previously. In the chronic SCI rats (> 45 days), no AADC cells expressed DA if there was no exogenous l-dopa application. However, following administration of a peripheral AADC inhibitor (carbidopa) with or without a monoamine oxidase inhibitor (pargyline) co-application, systemic administration of l-dopa resulted in ~94% of AADC cells becoming DA-immunopositive in the spinal cord below the lesion, whereas in normal or sham-operated rats none or very few of AADC cells became DA-immunopositive with the same treatment. Using tail electromyography, spontaneous tail muscle activity was increased nearly fivefold over the baseline level. When pretreated with a central AADC inhibitor (NSD-1015), further application of l-dopa failed to increase the motoneuron activity although the expression of DA in the AADC cells was not completely inhibited. These findings demonstrate that AADC cells in the spinal cord below the lesion gain the ability to produce DA from its precursor in response to SCI. This ability also enables the AADC cells to produce 5-HT and trace amines, and likely contributes to the development of hyperexcitability. These results might also be implicated for revealing the pathological mechanisms underlying l-dopa-induced dyskinesia in Parkinson's disease. PMID- 26830513 TI - What does theory-driven evaluation add to the analysis of self-reported outcomes of diabetes education? A comparative realist evaluation of a participatory patient education approach. AB - OBJECTIVE: To explore the effects of the Next Education (NEED) patient education approach in diabetes education. METHODS: We tested the use of the NEED approach at eight intervention sites (n=193). Six additional sites served as controls (n=58). Data were collected through questionnaires, interviews and observations. We analysed data using descriptive statistics, logistic regression and systematic text condensation. RESULTS: Results from logistic regression demonstrated better overall assessment of education program experiences and enhanced self-reported improvements in maintaining medications correctly among patients from intervention sites, as compared to control sites. Interviews and observations suggested that improvements in health behavior could be explained by mechanisms related to the education setting, including using person-centeredness and dialogue. However, similar mechanisms were observed at control sites. Observations suggested that the quality of group dynamics, patients' motivation and educators' ability to facilitate participation in education, supported by the NEED approach, contributed to better results at intervention sites. CONCLUSION: The use of participatory approaches and, in particular, the NEED patient education approach in group-based diabetes education improved self-management skills and health behavior outcomes among individuals with diabetes. PRACTICE IMPLICATIONS: The use of dialogue tools in diabetes education is advised for educators. PMID- 26830514 TI - Health literacy is independently associated with self-care behavior in patients with heart failure. AB - OBJECTIVE: Health literacy (HL) has been recognized as an important concept in patient education and disease management for heart failure (HF). However, previous studies on HL have focused predominantly on the relationships between functional HL (the ability to read and write), comprehensive HL including the ability to access information (communicative HL), and the ability to critically evaluate information (critical HL). Self-care behavior has not been evaluated. This study determined the relationship between functional, communicative, and critical HL and self-care behavior in HF patients. METHODS: Cross-sectional analysis of the data was completed for HL, HF-related knowledge, and HF-related self-care behaviors. Sociodemographic and clinical characteristics were also assessed. Multivariate linear regression analysis was used to estimate the associations between literacy and self-care behavior. RESULTS: 249 patients with HF were assessed (mean age, 67.7+/-13.9years). Patients with low HL had poorer knowledge and self-care behavior than those with high HL. Critical HL was an independent determinant of self-care behavior (sbeta=-0.154, P=0.027). CONCLUSIONS: Critical HL was independently associated with self-care behavior in HF patients. PRACTICE IMPLICATIONS: Effective intervention should be developed to improve patient skills for critically analyzing information and making decisions. PMID- 26830515 TI - The critical role of communications in a multilevel obesity-prevention intervention: Lessons learned for alcohol educators. AB - OBJECTIVE: Multilevel interventions to prevent underage drinking are more effective than individual-level strategies, and messaging campaigns are key to such approaches. Recognizing the benefits of translating best practices across public health domains, this paper details the communications campaign from Shape Up Somerville (SUS), an exemplar for multilevel community-based approaches to address pediatric obesity, highlighting lessons learned for alcohol educators. METHODS: All elements of SUS, including the communications strategy, were developed collaboratively with local partners. Communication initiatives included community-engaged brand development to unify diverse intervention components; school-based communications to promote new opportunities for healthy eating and physical activity; and media partnerships to promote healthy behaviors community wide. RESULTS: The overall SUS intervention was effective in reducing prevalence of overweight/obesity among first- to third-graders in Somerville relative to control communities. Process evaluation showed that communications successfully reached diverse community segments and raised awareness of and receptivity to changes. CONCLUSIONS AND PRACTICE IMPLICATIONS: Communications campaigns are essential components of multilevel interventions addressing public health challenges including obesity and underage drinking. Such communications should be developed collaboratively with the target audience and stakeholders, designed to engage community members at multiple levels through multiple channels within a systems framework, and sustained through local partnerships. PMID- 26830517 TI - Stop Predatory Publishers Now: Act Collaboratively. PMID- 26830516 TI - A questionnaire identifying four key components of patient satisfaction with physician communication. AB - OBJECTIVE: To improve efficiency and retain the 4 factors of a reliable, valid interview satisfaction questionnaire (ISQ). METHOD: 105 residents conducted 301 patient-centered interviews with 10 simulated patients (SP). SPs portrayed three scenarios for each resident and completed the ISQ and the Communication Assessment Tool (CAT) after each. A confirmatory factor analysis (CFA) of the ISQ and CAT determined which items had >0.5 factor loadings and <0.1 error, criteria for retaining items in a shortened scale. RESULTS: After the CFA, 13 items were deleted resulting in a 12-item scale (RMSE=0.06) that confirmed the initial 4 factor structure of satisfaction with: open-endedness, empathy, confidence in the resident, and general. Scale reliability of each factor was high (Cronbach's alpha ranged from .74 to .93). Demonstrating concurrent validity, all four factors of the ISQ correlated highly with the one-factor CAT (r>.7, p<.001), and the second order unidimensional ISQ scale also correlated highly with the CAT (r=.83, p<.001). CONCLUSIONS: The ISQ is an efficient, reliable, and valid instrument that uniquely deconstructs satisfaction with the patient-physician interaction into 4 key components. PRACTICE IMPLICATIONS: The 4 components provide a means for better understanding poor satisfaction results. PMID- 26830518 TI - Nursing education in Bangladesh: a social business model. AB - INTRODUCTION AND AIM: The aim of this project was to develop a quality nurse education programme in Bangladesh. A sustainable social business financial model was used. The project is a collaboration between Glasgow Caledonian University and the Grameen Health Care Trust. It contributes to the UN development agenda, eradication of poverty, sustainability and the development of global partnerships. BACKGROUND: There is an acute shortage of nurses in Bangladesh but many young women who wish to become nurses are unable to do so. Women are discriminated against, have few leadership opportunities and poverty affects large proportions of rural society. DEVELOPMENT: The collaboration between the University and the Trust provides the necessary input to ensure a quality nursing programme. A business plan was developed, competency-based teaching introduced, infrastructure and financial management processes were set-up and an evaluation framework was put in place. EVALUATION: The systems evaluation framework monitors the financial status of the College and the effects of the programme on students. The social business model, providing access to educational loans, has enabled 118 students to graduate into employment. The College is currently on target to be financially sustainable by 2016. DISCUSSION: This project outlines a business model that tackles poverty, gender equality and contributes to the human resource deficit. Young women are equipped as change agents and leaders. CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: The social business model provides a mechanism for releasing funds for education to those who are impoverished. It provides a viable option for increasing the number of well-educated nurse leaders in developing countries. PMID- 26830519 TI - When Nutraceuticals Reinforce Drugs Side Effects: A Case Report. AB - INTRODUCTION: Nutraceutical is a term applied for a plethora of products ranging from isolated nutrients, herbal products to dietary supplements and recently, the interest for a nutraceutical approach to lipid and metabolic disorders is growing. Patients with metabolic conditions seem to appreciate a therapeutic management that does not involve drug treatment, particularly for the side effects due to statins, a class of drug used for lipid disorders. Statins directly induce skeletal muscle injury and in the elderly patients, under polytherapy treatments, this risk relies to an increase in adverse drug reactions due to drug interactions. CASE DESCRIPTION: Herein we report a 70-year-old woman under polytherapy who developed rhabdomyolysis after starting the administration of a dietary supplement containing monacolin K. Using the Drug Interaction Probability Scale, we postulated that rhabdomyolysis was possibly related to a drug interaction between sertraline, rosuvastatin and monacolin K. These treatments were discontinued leading to a remission of both clinical symptoms and biochemical parameters. CONCLUSION: This case report highlights how pharmacological treatment must be periodically reassessed, since elderly people could take drugs by themselves when they donot need. PMID- 26830520 TI - Anxiety symptoms during hospitalization of elderly are associated with increased risk of post-discharge falls. AB - BACKGROUND: The aim of this study was to test the association between anxiety at the time of hospitalization and falls occurring within one month of discharge, and to offer potential mechanisms for this association. METHODS: One-month, prospective cohort study of 556 older adults in two medical centers in Israel. Anxiety and functional decline were assessed during hospitalization and falls were assessed one month post-discharge. RESULTS: A total of 72 (12.9%) participants reported at least one fall during the 30-day post-discharge period. Controlling for demographics, functional decline and pre-morbid functional status, the odds of falls between discharge, and 1-month follow-up were almost twice as high among patients with anxiety symptoms (OR = 1.89, 95% CI: 1.04-3.48) compared with those who screened negative for anxiety. After accounting for in hospital functional decline, the relationship between anxiety symptoms and falls decreased by 11% (from OR = 2.13 to 1.89), indicating that the relationship between anxiety and falls was partially mediated by functional decline during hospitalization. CONCLUSIONS: Anxiety at time of hospitalization is associated with falls 30-days post-discharge, controlling for several well-known confounders. This relationship is partially mediated by functional decline. Identifying patients with anxiety for inclusion in targeted rehabilitation interventions may be an important component of fall prevention strategies. PMID- 26830521 TI - Single Accreditation System for Graduate Medical Education: An Opportunity for Lesbian, Gay, Bisexual, and Transgender Health Education Integration in Osteopathic Medicine. PMID- 26830523 TI - Effectiveness of the Complete Health Improvement Program in Reducing Risk Factors for Cardiovascular Disease in an Appalachian Population. AB - CONTEXT: In 11 counties in Appalachian Ohio, the self-reported prevalence of diabetes mellitus (11.3%) is higher than the state (7.8%) or national (7.2%) average. Direct medical costs for diabetes in the United States are estimated at $176 billion annually. Indirect costs from disability, work loss, and premature death add up to another $69 billion. OBJECTIVE: To determine the effectiveness of the Complete Health Improvement Program (CHIP) in reducing cardiovascular disease (CVD) risk factors in a sample of Appalachian participants with elevated fasting blood glucose (FBG) levels or a diagnosis of type 2 diabetes mellitus (T2DM). METHODS: In a retrospective study, data from 6 CHIP cohorts conducted in Appalachian Ohio from 2011 to 2012 were combined and analyzed for short-term changes in CVD risk factors from baseline. This study focused on a subsample of the overall CHIP, whose participants had elevated FBG levels or T2DM. Statistical analysis was completed by calculating means and SDs and using paired t tests to compare differences in variables. RESULTS: After the CHIP intervention, 110 participants with baseline elevated FBG levels showed notable reductions in FBG levels, total cholesterol, low-density lipoprotein cholesterol, body mass index, and systolic blood pressure (all P values <.001). Likewise, participants in the subsample with T2DM experienced reductions in all CVD risk factors (all P values <.05). CONCLUSION: The CHIP lifestyle intervention was effective in reducing CVD risk factors in this Appalachian population with elevated FBG levels or with T2DM. PMID- 26830524 TI - Osteopathic Physicians on the Editorial Boards of Major Medical Journals Over the Past 30 Years. AB - CONTEXT: With the recent merger of the American Osteopathic Association and the Accreditation Council for Graduate Medical Education, new standards may be established for scholarly activity criteria and designation for each specialty. OBJECTIVE: To determine the percentage of osteopathic physicians on editorial boards in general and specialty medical journals and to compare the participation of osteopathic vs allopathic physicians and other health care researchers in editorial activities. METHODS: The number of osteopathic and allopathic physicians and other health care professionals serving as editor in chief, associate editor, editorial board member, emeritus editor, or in other editorial positions was examined in 8 major medical journals (New England Journal of Medicine, JAMA, Annals of Internal Medicine, Annals of Surgery, Annals of Emergency Medicine, Annals of Family Medicine, Obstetrics and Gynecology, and Pediatrics) published during the past 30 years. RESULTS: The number of editorial board positions increased during the past 30 years, with Annals of Surgery adding the most positions (64). When compared with allopathic physicians in all fields of medicine, the number of osteopathic physicians serving on an editorial board of a medical journal was significantly less (P<.001). When all editorial positions were combined, osteopathic physicians occupied 0.15% of all positions. CONCLUSION: A disparity exists between the numbers of osteopathic vs allopathic physicians in editorial positions in the core disciplines of medicine. Further investigation into the reasons why few osteopathic physicians serve in editorial roles is needed. PMID- 26830525 TI - How to Monitor and Advise Vegans to Ensure Adequate Nutrient Intake. PMID- 26830526 TI - Burnout Among Osteopathic Residents: A Cross-sectional Analysis. AB - CONTEXT: Burnout is a known problem among physicians in training but has not been extensively studied in osteopathic residents. OBJECTIVE: To evaluate the relationship of burnout to sex, age, marital status, and residency program type (surgical vs nonsurgical) and length (3, 4, 5, or 6 years) across 12 residency programs at Doctors Hospital in Columbus, Ohio. METHODS: An anonymous, voluntary questionnaire was given to residents in their 10th month of residency. Thirty questions were provided, including general background questions and the Maslach Burnout Inventory Human Services Survey to assess burnout. RESULTS: A total of 131 of 180 residents (72.8%) returned the questionnaire, and 129 provided complete responses in most categories. Of the 129 respondents, 89 (69.0%) reported emotional exhaustion and 96 (74.4%) reported depersonalization at a moderate or high level. In addition, 70 respondents (54.4%) experienced a moderate or high level of burnout in relation to personal accomplishment. No statistically significant association was found between the burnout factors (emotional exhaustion, depersonalization, and personal accomplishment) and sex, age, marital status, and residency program type and length. CONCLUSIONS: The majority of the osteopathic residents surveyed reported experiencing burnout. More data on burnout among osteopathic residents and associated factors are needed. PMID- 26830527 TI - Establishing a Professionalism Score in an Osteopathic Manipulative Medicine Curriculum. AB - As osteopathic medical education shifts to competency-based learning, course curriculums must adapt to measure behavioral milestones in addition to traditional knowledge and technical skills. Of the core competencies, medical professionalism or lack thereof has been shown to correlate with future state disciplinary board action; therefore, early identification of poor professionalism and intervention is imperative. However, performance indicators, such as humanistic behavior and primacy of patient need, are difficult to measure in most first- and second-year medical school courses. Therefore, A.T. Still University-Kirksville College of Osteopathic Medicine developed a rubric to objectively measure professionalism within the first- and second-year osteopathic manipulative medicine curriculum. The rubric assesses such measures as timeliness and professional appearance. In the present article, the author describes the grading rubric and the methods for implementing a professionalism score within an osteopathic manipulative medicine curriculum. PMID- 26830528 TI - Abdominal Trigger Points and Psychological Function. AB - Myofascial trigger points (TPs) are a poorly understood phenomenon involving the myofascial system and its related neural, lymphatic, and circulatory elements. Compression or massage of a TP causes localized pain and may cause referred pain and autonomic phenomena. The authors describe a 58-year-old woman who experienced precipitation of substantial psychological symptoms directly related to her treatment for a lower abdominal TP. Her symptoms resolved after 2 weeks of receiving high-velocity, low-amplitude manipulation and soft tissue massage. Particularly in the abdomen, TPs may be associated with psychological reactions as well as physical aspects of bodily function. PMID- 26830530 TI - The Man in Room 7218. PMID- 26830529 TI - Pneumorrhachis. PMID- 26830531 TI - Interrelationship of Structure and Function in Maxillofacial Fractures. AB - Surgical fixation of maxillofacial fractures can be associated with a myriad of surgical complications. Specific complications correlate with the type of fracture. The authors present a case of multiple maxillofacial fractures, briefly review various types of fractures, and discuss the operative decision-making process. This case report serves as an important reminder that the operative decision-making process should take into account a patient's entire clinical condition. PMID- 26830532 TI - Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis. AB - The aim of this study was to describe the mutational characteristics in Korean hereditary spherocytosis (HS) patients. Relevant literatures including genetically confirmed cases with well-documented clinical summaries and relevant information were also reviewed to investigate the mutational gene- or domain specific laboratory and clinical association. Twenty-five HS patients carried one heterozygous mutation of ANK1 (n = 13) or SPTB (n = 12) but not in SPTA1, SLC4A1, or EPB42. Deleterious mutations including frameshift, nonsense, and splice site mutations were identified in 91% (21/23), and non-hotspot mutations were dispersed across multiple exons. Genotype-phenotype correlation was clarified after combined analysis of the cases and the literature review; anemia was most severe in HS patients with mutations on the ANK1 spectrin-binding domain (p < 0.05), and SPTB mutations in HS patients spared the tetramerization domain in which mutations of hereditary elliptocytosis and pyropoikilocytosis are located. Splenectomy (17/75) was more frequent in ANK1 mutant HS (32%) than in HS with SPTB mutation (10%) (p = 0.028). Aplastic crisis occurred in 32.0% of the patients (8/25; 3 ANK1 and 5 SPTB), and parvovirus B19 was detected in 88%. The study clarifies ANK1 or SPTB mutational characteristics in HS Korean patients. The genetic association of laboratory and clinical aspects suggests comprehensive considerations for genetic-based management of HS. PMID- 26830533 TI - Blood donation and risk of polycythemia vera. AB - BACKGROUND: It has been suggested that blood donors could have an increased risk of polycythemia vera (PV). However, no study has assessed whether frequent donors have a higher PV risk than less frequent donors. STUDY DESIGN AND METHODS: From the Scandinavian Donations and Transfusions (SCANDAT2) database, we established a cohort of blood donors who had donated whole blood at least once between 1980 and 2012. Within this cohort we first assessed the risk of PV, comparing the donors to the general population using standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs). To assess the association between frequency of blood donation and risk of PV we then conducted a case-control study nested within the cohort, where we compared prior donation activity among donors who were diagnosed with PV and matched controls. Here odds ratios (ORs) were used as measures of relative risk comparing donors with different donation frequency. RESULTS: Among 1.4 million donors in the cohort a total of 271 donors developed PV, yielding a SIR of 1.00 (95% CI, 0.89-1.13) compared to the general population. The nested case-control study showed no association between donation frequency and risk of PV. The OR of PV comparing donors who had made at least 33 donations in the period from 3 to 22 years before diagnosis of the case, to donors with one to eight donations in the same period was 1.01 (95% CI, 0.51 1.97). CONCLUSIONS: We find no evidence of excess risk of PV among blood donors or of an association between donation frequency and PV risk. PMID- 26830534 TI - Evidence by chromatography and mass spectrometry that inorganic nitrite induces S glutathionylation of hemoglobin in human red blood cells. AB - Previously we found by HPLC with fluorescence detection that inorganic nitrite induces oxidation of glutathione (GSH) to its disulfide (GSSG) in intact and more abundantly in lyzed red blood cells (RBCs) from healthy humans. In the present work, we performed MS-based protein analysis and observed that nitrite (range, 0 20mM) induces formation of S-glutathionyl hemoglobin (HbSSG) at cysteine (Cys) beta93 and beta112 of oxyhemoglobin (HbO2) in lyzed human RBCs (range, 6-8mM HbO2). Hemoglobin species were isolated from incubation mixtures of nitrite in lyzed RBCs by ultrafiltration or affinity chromatography and analyzed by HPLC and LC-MS/MS. The mechanism likely involves inhibition of catalase activity by nitrite (IC50, 9 MUM), which allows H2O2 to accumulate and oxidize Cys moieties of oxyhemoglobin and erythrocytic GSH to form HbSSG in addition to GSSG. In freshly prepared hemolysate samples, nitrite induced release of superoxide and molecular oxygen. In the presence of paracetamol and nitrite in hemolysate samples, 3-nitro-paracetamol was detected. Nitrite also induced S-nitroso hemoglobin (HbSNO) formation in low yield (i.e., 0.1%). Synthetic cysteine (Cys), glutathione (GSH), N-acetylcysteine (NAC) and N-acetylcysteine ethyl ester (NACET) inhibited nitrite-induced modifications of oxyhemoglobin including methemoglobin, HbSSG (CysSH >> NACET >> GSH ~ NAC; thiol concentration, 50 MUM) and HbSNO. Nitrite-induced oxidative modifications may alter physiological hemoglobin functions and may require alternative treatments for conditions associated with oxidized hemoglobin like in nitrite-induced methemoglobinemia. Accumulation of soluble Cys in RBCs via oral administration of NACET could be a new promising strategy to prevent nitrite-induced methemoglobinemia by nitrite and other oxidants. PMID- 26830535 TI - The pharmacokinetic characters of simvastatin after co-administration with Shexiang Baoxin Pill in healthy volunteers' plasma. AB - To investigate the effect of Shexiang Baoxin Pill (SBP), a tranditional Chinese medicine, on the pharmacokinetic (PK) parameters of simvastatin in healthy volunteers' plasma, a quantitative method was developed using an Agilent G6410A rapid performance liquid chromatography (RPLC) coupled with triple quadrupole mass spectrometry system. The established method was rapid with high extraction recovery and successfully applied for the determination of simvastatin in plasma of 16 healthy volunteers. The results demonstrated that the MRT(0-infinity), T1/2 and Tmax value of simvastatin were significantly decreased, while the AUC(0-t) and Cmax values of smivastatin were increased by SBP. The pharmacokinetic study demonstrated that the metabolism parameters of simvastatin could be affected by SBP and the potential drug-drug interaction should be noted in the future clinical practice. PMID- 26830536 TI - Routes to improve binding capacities of affinity resins demonstrated for Protein A chromatography. AB - Protein A chromatography is a well-established platform in downstream purification of monoclonal antibodies. Dynamic binding capacities are continuously increasing with almost every newly launched Protein A resin. Nevertheless, binding capacities of affinity chromatography resins cannot compete with binding capacities obtained with modern ion exchange media. Capacities of affinity resins are roughly 50% lower. High binding capacities of ion exchange media are supported by spacer technologies. In this article, we review existing spacer technologies of affinity chromatography resins. A yet known effective approach to increase the dynamic binding capacity of Protein A resins is oligomerization of the particular Protein A motifs. This resembles the tentacle technology used in ion exchange chromatography. Dynamic binding capacities of a hexameric ligand are roughly twice as high compared to capacities obtained with a tetrameric ligand. Further capacity increases up to 130mg/ml can be realized with the hexamer ligand, if the sodium phosphate buffer concentration is increased from 20 to 100mM. Equilibrium isotherms revealed a BET shape for the hexamer ligand at monoclonal antibody liquid phase concentrations higher than 9mg/ml. The apparent multilayer formation may be due to hydrophobic forces. Other quality attributes such as recovery, aggregate content, and overall purity of the captured monoclonal antibody are not affected. PMID- 26830537 TI - Affinity approaches in RNAi-based therapeutics purification. AB - The recent investigation on RNA interference (RNAi) related mechanisms and applications led to an increased awareness of the importance of RNA in biology. Nowadays, RNAi-based technology has emerged as a potentially powerful tool for silencing gene expression, being exploited to develop new therapeutics for treating a vast number of human disease conditions, as it is expected that this technology can be translated onto clinical applications in a near future. This approach makes use of a large number of small (namely short interfering RNAs, microRNAs and PIWI-interacting RNAs) and long non-coding RNAs (ncRNAs), which are likely to have a crucial role as the next generation therapeutics. The commercial and biomedical interest in these RNAi-based therapy applications have fostered the need to develop innovative procedures to easily and efficiently purify RNA, aiming to obtain the final product with high purity degree, good quality and biological activity. Recently, affinity chromatography has been applied to ncRNAs purification, in view of the high specificity. Therefore, this article intends to review the biogenesis pathways of regulatory ncRNAs and also to discuss the most significant and recent developments as well as applications of affinity chromatography in the challenging task of purifying ncRNAs. In addition, the importance of affinity chromatography in ncRNAs purification is addressed and prospects for what is forthcoming are presented. PMID- 26830538 TI - Erratum for Rattenbacher et al., Analysis of CUGBP1 Targets Identifies GU-Repeat Sequences That Mediate Rapid mRNA Decay. PMID- 26830540 TI - T Cell Vaccinology: Beyond the Reflection of Infectious Responses. AB - Inducing sustained, robust CD8(+) T cell responses is necessary for therapeutic intervention in chronic infectious diseases and cancer. Unfortunately, most adjuvant formulations fail to induce substantial cellular immunity in humans. Attenuated acute infectious agents induce strong CD8(+) T cell immunity, and are thought to therefore represent a good road map for guiding the development of subunit vaccines capable of inducing the same. However, recent evidence suggests that this assumption may need reconsideration. Here we provide an overview of subunit vaccine history as it pertains to instigating T cell responses. We argue that in light of evidence demonstrating that T cell responses to vaccination differ from those induced by infectious challenge, research in pursuit of cellular immunity-inducing vaccine adjuvants should no longer follow only the infection paradigm. PMID- 26830541 TI - Humoral Fingerprinting of Immune Responses: 'Super-Resolution', High-Dimensional Serology. AB - In a recent study, Chung et al. report the development of a high-dimensional approach to assess humoral responses to immune perturbation that goes beyond antibody neutralization and titers. This approach enables the identification of potentially novel correlates and mechanisms of protective immunity to HIV vaccination, thus offering a glimpse of how dense phenotyping of serological responses coupled with bioinformatics analysis could lead to much-sought-after markers of protective vaccination responses. PMID- 26830542 TI - Optical Coherence Tomography Angiography of Shallow Irregular Pigment Epithelial Detachments in Pachychoroid Spectrum Disease. PMID- 26830543 TI - [Time point and methods for emergency killing in cattle]. AB - Emergency killing is defined as the killing of injured or ill animals to avoid excessive pain or harm. Decision-making for emergency killing or a prolonged therapy can be difficult and has to be based on the case history and results of the clinical examination contributing to the prognosis, particularly in downer cows. Evaluation of enzyme activities and total bilirubin can be used as additional factors pointing to a guarded prognosis; however, none of these parameters provides a clear cut-off value indicating a poor prognosis and mandatory emergency killing. Euthanasia by intravenous drug application is seen as the least stressful method of killing and should therefore always be the first method of choice for emergency killing in cattle. Drugs containing pentobarbital as well as a combination of three different drugs (T61-Injektionslosung, MSD Animal Health) are available for euthanasia in cattle. All drugs must be administered by a veterinarian. Before application of pentobarbital, an animal should be deeply sedated. The administration of T61 requires anaesthesia of the animal and it is not licensed for use in pregnant animals. Alternative methods for emeragency killing, including captive bolt stunning and the use of firearms, although not regularly performed by veterinarians, should be assessed concerning their correct application and performance. When captive bolt stunning or emergency killing using firearms is performed, the correct position of the device is crucial as well as a quick exsanguination or the application of a pithing rod for the actual killing of the animal after captive bolt stunning. In addition to medical considerations, economic and personal factors contribute to the decision about emergency killing in cattle. Therefore, veterinarians should aim to evaluate each case thoroughly based on personal knowledge and experience, case history, clinical findings and laboratory parameters to avoid prolonged suffering of the animal. PMID- 26830544 TI - The relationship between physician humility, physician-patient communication, and patient health. AB - OBJECTIVE: Cultural portrayals of physicians suggest an unclear and even contradictory role for humility in the physician-patient relationship. Despite the social importance of humility, however, little empirical research has linked humility in physicians with patient outcomes or the characteristics of the doctor patient visit. The present study investigated the relationship between physician humility, physician-patient communication, and patients' perceptions of their health during a planned medical visit. METHODS: Primary care physician-patient interactions (297 patients across 100 physicians) were rated for the physician's humility and the effectiveness of the physician-patient communication. Additionally, patients reported their overall health and physicians and patients reported their satisfaction with the interaction. RESULTS: Within-physician fluctuations in physician humility and self-reported patient health positively predicted one another, and mean-level differences in physician humility predicted effective physician-patient communication, even when controlling for the patient's and physician's satisfaction with the visit and the physician's frustration with the patient. CONCLUSIONS: The results suggest that humble, rather than paternalistic or arrogant, physicians are most effective at working with their patients. PRACTICE IMPLICATIONS: Interventions to improve physician humility may promote better communication between health care providers and patients, and, in turn, better patient outcomes. PMID- 26830545 TI - Spontaneously occurring lymphohematopoietic tumors in three young Sprague Dawley rats. AB - To assess the toxicological and pharmacological effects of chemicals, it is important to know what kinds of neoplasms naturally occur in the early life of laboratory animals. In the present study, we identified three spontaneous hematopoietic tumors in three of 52 young female Sprague-Dawley rats used in a pharmacological study. These cases included two rats (Case 1 and 2) from a sesame oil-treated group and one rat (Case 3) from a chemical-treated group in the same single gavage study. Case 1 rapidly lost body weight at 13 weeks of age without any clinical signs and died. Round lymphoid tumor cells were found in the spleen, liver, bone marrow, and pancreas. The tumor cells were immunohistochemically positive for CD3 and PCNA, which is suggestive of malignant T-cell lymphoma. Cases 2 and 3 had rapid body weight loss at 14 and 16 weeks of age, respectively, exhibited severe anemia, hypolocomotion, and decreased body temperature, and were euthanized due to a poor prognosis based on severe clinical signs. Pleomorphic large tumor cells were found in the spleen, liver, bone marrow, lymph nodes, heart, kidneys, lung, pancreas, adrenal glands, pituitary gland, ovaries, Harderian gland, and/or eyes. The tumor cells were immunoreactive for CD34, lysozyme, and PCNA, which is suggestive of myeloid leukemia. These cases might provide useful historical control information for rat toxicity studies. PMID- 26830546 TI - Fluorine-18-fluorodeoxyglucose positron emission tomography to evaluate recurrent gastric cancer after surgical resection: a systematic review and meta-analysis. AB - We aimed to explore the diagnostic accuracy of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) for detection of gastric cancer recurrence after surgical resection through a systematic review and meta-analysis. "PubMed", EMBASE, Web of Knowledge and Springer, from the beginning of 2002 to Feb 2015, were searched for studies evaluating the diagnostic performance of 18F-FDG PET in detecting recurrent gastric cancer. We calculated sensitivities, specificities, diagnostic odds ratios and likelihood ratios, and constructed summary receiver operating characteristic curves. Fourteen studies (828 patients) were included. On a per-patient basis, the forest plots showed that the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of (18)F-FDG PET or PET/CT were 0.85 [95 % confidence interval (CI) 0.75-0.92], 0.78 (95 % CI 0.72-0.84), 3.9 (95 % CI 2.9-5.4), 0.19 (95 % CI 0.11 0.34), and 21 (95 % CI 9-47), respectively. On a per-lesion basis, the pooled sensitivity was 0.75 (95 % CI 0.61-0.86). The area under the SROC curve of PET/CT on the basis of per-patient was 0.86. (18)F-FDG PET had great value in the detection of gastric cancer recurrence after surgical resection. The sensitivities of (18)F-FDG PET were 85 and 75 %, respectively, on per-patient basis and on per-lesion basis. PMID- 26830547 TI - Circulating antibodies to alpha-enolase and phospholipase A2 receptor and composition of glomerular deposits in Japanese patients with primary or secondary membranous nephropathy. AB - BACKGROUND: Phospholipase A2 receptor (PLA2R) is recognized as a target antigen in primary membranous nephropathy (MN); Anti-alpha-enolase antibody in primary and secondary MN has been proposed, however, little is known about the potential contribution of alpha-enolase to the pathogenesis of MN. METHODS: We evaluated circulating antibodies to alpha-enolase by a dot blotting system and PLA2R by indirect immunofluorescence, and glomerular deposition of these proteins in 25 patients with primary MN, 20 patients with secondary MN, 44 patients with collagen disease or severe infection, 60 patients with nephritis (each ten patients of IgA nephropathy, focal segmental gloemrulosclerosis, minimal change nephrotic syndrome, membranoproliferative glomeurlonephritis, diabetic glomerulosclerosis, and tubulointerstitial nephritis) as disease control, and 20 healthy subjects. RESULTS: In primary MN, 18 of 25 sera (72 %) showed anti-alpha enolase antibody (IgG1 and IgG4, 11 pts; IgG4 alone, six pts; IgG1 alone, one pt). In secondary MN, 15 of 20 sera (75 %) contained anti-alpha-enolase antibody (IgG1 and IgG3, 13 pts; IgG3 alone, two pts). No circulating anti-alpha-enolase antibody was found in 44 collagen diseases or septic patients, 60 nephritis without MN, and 20 healthy subjects. Twelve of 25 sera (48 %) from patients with primary MN were positive for anti-PLA2R antibody, whereas all patients with secondary MN were negative. Eight of the 12 PLA2R-positive patients (67 %) with primary MN also had anti alpha-enolase antibody. Although PLA2R antigen was present in a subepithelial pattern in 10 of 19 (52 %) patients with primary MN, alpha-enolase was never detected in glomerular deposits in 19 and ten patients with primary and secondary MN, respectively. CONCLUSIONS: Circulating anti-alpha enolase antibodies are highly present in both primary and secondary MN (about 70 %, respectively), while anti-PLA2R antibodies are specific for primary MN (48 %) with a prevalence apparently lower in the Japanese population than in Chinese and Caucasian populations. The absence of alpha-enolase from subepithelial immune deposits suggests that anti-alpha-enolase antibodies do not contribute directly to immune-deposit formation, although they may have other pathogenic effects. PMID- 26830549 TI - Incidence of hypocalcemia in patients receiving denosumab for prevention of skeletal-related events in bone metastasis. AB - Background Denosumab therapy is commonly used for the prevention of skeletal related events in patients with bone metastasis. However, a common side effect of denosumab is hypocalcemia. Objective The aim of the study is to determine the incidence of hypocalcemia in patients receiving denosumab for prevention of skeletal-related events in bone metastasis and evaluate risk factors for developing hypocalcemia. Methods This was a retrospective medication use evaluation reviewing the incidence of hypocalcemia in patients receiving outpatient denosumab for prevention of skeletal-related events at Yale-New Haven Hospital. Additionally, various risk factors were reviewed to determine their risk of developing hypocalcemia. Results As per Common Terminology Criteria for Adverse Events v4.03, of the 106 patients included in the study population, 37 (35%) patients had an incidence of hypocalcemia within 30 days of denosumab administration. Fourteen patients (13.2%) had an incidence of grade 1, 13 patients (12.3%) had an incidence of grade 2 hypocalcemia, and 7 patients (6.6%) had an incidence of grade 3 hypocalcemia. Grade 4 hypocalcemia occurred in three (2.8%) patients. Calcium supplementation did not decrease the risk of developing hypocalcemia. Patients who had one or more episodes of acute kidney insufficiency were at a higher risk of developing hypocalcemia (odds ratio = 7.5 (95% confidence interval = 1.8-36.3), p = 0.001). Conclusion This study found that the overall incidence of hypocalcemia and severe hypocalcemia was higher than reported in clinical trials. Additionally, calcium supplementation did not have an effect on incidence of hypocalcemia, while patients who experienced acute kidney insufficiency while on denosumab had a higher likelihood of developing hypocalcemia. PMID- 26830548 TI - Reduction of proteinuria by therapeutic intervention improves the renal outcome of elderly patients with IgA nephropathy. AB - BACKGROUND: The number of elderly patients with IgA nephropathy (IgAN) is increasing in parallel with the increased longevity in the general population. However, information is limited regarding the characteristics of such patients. METHODS: IgAN patients who were >=60 years of age at diagnosis were retrospectively analyzed. The clinicopathological features at biopsy, therapies during the follow-up period, renal outcomes and extrarenal complications were evaluated. RESULTS: The characteristics of a total of 87 patients were as follows (mean values): 65 years of age, an eGFR of 47 mL/min/1.73 m2, and urinary protein excretion (UPE) of 1.9 g/day. In the initial 1-year follow-up period, UPE decreased from 2.4 to 0.4 g/day in patients treated with corticosteroids and 1.4 to 0.8 g/day in patients treated with conservative therapies, including renin angiotensin system blockade. During the observation period, 26 % of the patients who received corticosteroids and 38 % of the patients treated with conservative therapies showed a >=30 % decrease in their eGFR or reached end-stage renal disease. In the analysis of all patients, UPE at 1 year after the diagnosis was identified to be an independent predictor of the subsequent loss of renal function. However, neither corticosteroid therapy nor conservative therapies was identified to be an independent valuable. There was no significant difference in the incidence of the extrarenal complications between patients treated with corticosteroids and those with conservative therapies. CONCLUSION: In elderly IgAN patients, the reduction of proteinuria by therapeutic interventions may lead to better renal outcomes without causing severe extrarenal complications. PMID- 26830551 TI - Intracranial arterial abnormalities in patients with late onset Pompe disease (LOPD). AB - BACKGROUND AND OBJECTIVES: Pompe disease is a rare metabolic disorder due to lysosomal alpha-glucosidase (GAA) deficiency. It is considered as a multi systemic disease since, although glycogen accumulation is largely prominent in heart, skeletal and respiratory muscles, other organs can also be affected. As regards the vascular system, few reports have documented cerebrovascular malformations in Pompe patients. The aim of this study was to define the presence and type of intracranial arterial abnormalities in a cohort of late onset Pompe disease (LOPD) patients. METHODS: We have studied 21 LOPD patients with cerebral CT angiography (CTA), using maximum intensity projection and volume rendering technique for 3D-image reconstruction. RESULTS: We found intracranial arterial abnormalities in 13/21 patients (62 %), of whom: 2/21 patients (9.5 %) showed an unruptured intracranial aneurysm (respectively 2 and 4 mm), 10/21 (47 %) had a vertebrobasilar dolichoectasia (VBD) and 1/21 a basilar artery fenestration. Signs of lacunar encephalopathy (insular, capsular and frontal subcortical lesions) were detected in 13/21 patients (62 %) and this correlated with the presence of respiratory impairment (p = 0.017). CONCLUSIONS: These findings differ from what has been previously observed in healthy, aged-matched populations and confirm that cerebral arteries abnormalities, mainly involving the posterior circle, are not so rare in LOPD patients and are often accompanied by a lacunar encephalopathy that might represent a hypoxic-ischemic origin. A CTA or an MRA is recommended, in LOPD patients, for early detection of cerebrovascular malformations as they could lead to life-threatening events such as sub-arachnoid haemorrhage or brainstem compression. PMID- 26830550 TI - Mildly compromised tetrahydrobiopterin cofactor biosynthesis due to Pts variants leads to unusual body fat distribution and abdominal obesity in mice. AB - Tetrahydrobiopterin (BH4) is an essential cofactor for the aromatic amino acid hydroxylases, alkylglycerol monooxygenase, and nitric oxide synthases (NOS). Inborn errors of BH4 metabolism lead to severe insufficiency of brain monoamine neurotransmitters while augmentation of BH4 by supplementation or stimulation of its biosynthesis is thought to ameliorate endothelial NOS (eNOS) dysfunction, to protect from (cardio-) vascular disease and/or prevent obesity and development of the metabolic syndrome. We have previously reported that homozygous knock-out mice for the 6-pyruvolytetrahydropterin synthase (PTPS; Pts-ko/ko) mice with no BH4 biosynthesis die after birth. Here we generated a Pts-knock-in (Pts-ki) allele expressing the murine PTPS-p.Arg15Cys with low residual activity (15% of wild-type in vitro) and investigated homozygous (Pts-ki/ki) and compound heterozygous (Pts-ki/ko) mutants. All mice showed normal viability and depending on the severity of the Pts alleles exhibited up to 90% reduction of PTPS activity concomitant with neopterin elevation and mild reduction of total biopterin while blood L-phenylalanine and brain monoamine neurotransmitters were unaffected. Yet, adult mutant mice with compromised PTPS activity (i.e., Pts-ki/ko, Pts-ki/ki or Pts-ko/wt) had increased body weight and elevated intra-abdominal fat. Comprehensive phenotyping of Pts-ki/ki mice revealed alterations in energy metabolism with proportionally higher fat content but lower lean mass, and increased blood glucose and cholesterol. Transcriptome analysis indicated changes in glucose and lipid metabolism. Furthermore, differentially expressed genes associated with obesity, weight loss, hepatic steatosis, and insulin sensitivity were consistent with the observed phenotypic alterations. We conclude that reduced PTPS activity concomitant with mildly compromised BH4-biosynthesis leads to abnormal body fat distribution and abdominal obesity at least in mice. This study associates a novel single gene mutation with monogenic forms of obesity. PMID- 26830553 TI - Microwave-assisted isomerisation of lactose to lactulose and Maillard conjugation of lactulose and lactose with whey proteins and peptides. AB - Lactose was isomerised to lactulose by microwave heating and purified by a methanolic procedure to a product with approximately 72% lactulose content. Afterwards, lactose and the lactulose-rich product (PLu) were conjugated with either whey protein isolate (WPI) or its antioxidant hydrolysate (WPH) through microwaving. Lactose had a higher Maillard reactivity than PLu, and WPH was more reactive than WPI. The browning intensity of WPI-sugar systems was however higher than that of WPH-sugar pairs. Atomic force microscopy showed larger (up to ~103 nm) particles for WPI-PLu conjugates compared to WPH-PLu counterparts (up to ~39 nm). The Maillard conjugation progressively increased the radical-scavenging activity of WPI/WPH-sugar pairs with increasing conjugation time and improved the foaming properties of WPI and WPH. The WPI/WPH-sugar conjugates showed higher solubility and emulsification index than unreacted counterpart pairs. For native WPI, beta-lactoglobulin was not degraded by in vitro gastric digestion, whereas for WPH-PLu conjugates degraded completely. PMID- 26830552 TI - Withdrawal of dopamine agonist therapy in prolactinomas: In which patients and when? AB - PURPOSE: The aim of the study was to assess the effect of dopamine agonist (DA) withdrawal, the current recurrence rate of hyperprolactinemia, and possible factors that predict recurrence in patients with prolactinoma. METHODS: We evaluated DA withdrawal in 67 patients with prolactinoma (50 female/17 male) who received DA treatment for at least 2 years and showed normalization of prolactin (PRL) levels and tumor disappearance or >=50 % tumor shrinkage, retrospectively. Accordingly, patients were divided into two groups as remission and recurrence groups, and factors that predict recurrence were evaluated. RESULTS: The overall remission rate was 46 %; the remission ratios were 65 % in microprolactinomas and 36 % in macroprolactinomas. Remission rates were 39 % in the bromocriptine withdrawal group and 55 % in the cabergoline withdrawal group. The maximum tumor diameter and baseline PRL levels were significantly higher in the recurrence group (p = 0.001 and p = 0.003, respectively). The mean duration of DA therapy was significantly longer in the remission group (88.7 +/- 48.1 and 66.7 +/- 30.4 months, respectively, p = 0.026).The mean time to recurrence was 5.3 +/- 3.2 months. The mean PRL levels at recurrence time were significantly lower than baseline PRL levels (p = 0.001). CONCLUSION: The most important predictors of recurrence were maximum tumor diameter and baseline PRL levels in this study. The remission rate in our study group was higher, which was thought to be associated with the longer duration of DA treatment and that our patients were selected according to certain criteria. Despite these positive results, close monitoring is necessary for detection of early and late recurrence, especially within the first year after DA withdrawal. PMID- 26830554 TI - Magnetic solid phase extraction using ionic liquid-coated core-shell magnetic nanoparticles followed by high-performance liquid chromatography for determination of Rhodamine B in food samples. AB - Three hydrophobic ionic liquids (ILs) (1-butyl-3-methylimidazole hexafluorophosphate ([BMIM]PF6), 1-hexyl-3-methyl-imidazole hexafluoro-phosphate ([HMIM]PF6), and 1-octyl-3-methylimidazole hexafluorophosphate ([OMIM]PF6)) were used to coat Fe3O4@SiO2 nanoparticles (NPs) with core-shell structures to prepare magnetic solid phase extraction (MSPE) agents (Fe3O4@SiO2@IL). A novel method of MSPE coupled with high-performance liquid chromatography for the separation/analysis of Rhodamine B was then established. The results showed that Rhodamine B was adsorbed rapidly on Fe3O4@SiO2@[OMIM]PF6 and was released using ethanol. Under optimal conditions, the pre-concentration factor for the proposed method was 25. The linear range, limit of detection (LOD), correlation coefficient (R), and relative standard deviation (RSD) were found to be 0.50 150.00 MUgL(-1), 0.08 MUgL(-1), 0.9999, and 0.51% (n=3, c=10.00 MUgL(-1)), respectively. The Fe3O4@SiO2 NPs could be re-used up to 10 times. The method was successfully applied to the determination of Rhodamine B in food samples. PMID- 26830555 TI - Synthesis of tubular nanostructures from wheat bran albumins during proteolysis with V8 protease in the presence of calcium ions. AB - There are very few reports on the self-assembly of peptides derived from proteins of agro industrial byproducts origin. Although it has been claimed that purity is a determining factor in peptide self-assembly, whether proteins extracted using water along with other components also form self-assembled structures is not known. The results of this work prove that albumins from wheat bran, a byproduct obtained from the milling industry, can form tubular nanostructures during their hydrolysis with the V8 protease in the presence of Ca(2+). Electron microscopy of the hydrolysate revealed that under specific conditions, long filaments are formed, which are nanotubes of several microns in length, with inner and outer diameters of 100 and 200 nm, respectively. The infrared analysis of the hydrolysate identified (-)OOC-Ca(2+) interactions and changes in beta sheet content in response to variations in protein/V8/Ca(2+) molar ratios. A model that explains the probable mechanism of the observed self-assembly is discussed. PMID- 26830556 TI - Comparison of flavour qualities of three sourced Eriocheir sinensis. AB - Flavour qualities of three edible parts of three types of Chinese mitten crab from different areas were examined. The flavour profiles detected by E-tongue and E-nose showed that differences existed in tastes and odours among wild-caught crabs (WC), Yangcheng crabs (YC) and Chongming crabs (CM). The total free amino acids contents of WC were all at the highest level in meat, gonads and hepatopancreas. Ovaries had the highest nucleotides content and equivalent umami concentration (EUC) than other tissues in both female and male. The EUC was the highest in all parts of WC, followed by YC and CM. The total content of nine key volatile compounds was the highest for WC in the gonads and hepatopancreas; in the muscle, they were the highest in female YC and male CM, but the lowest for WC. PMID- 26830557 TI - Determination of malachite green in aquatic products based on magnetic molecularly imprinted polymers. AB - Magnetic molecularly imprinted polymers (MMIPs) were synthesized through precipitation polymerization using malachite green (MG) as template, methacrylic acid as monomer, ethylene dimethacrylate as crosslinker, and Fe3O4 magnetite as magnetic component. MMIPs were characterized by scanning electron microscopy, Fourier transform infrared spectrometry, and vibrating sample magnetometry. Under the optimum condition, the MMIPs obtained exhibited quick binding kinetics and high affinity to MG in the solution. Scatchard plot analysis revealed that the MMIPs contained only one type of binding site with dissociation constant of 24.0 MUg mL(-1). The selectivity experiment confirmed that the MMIPs exhibited higher selective binding capacity for MG than its structurally related compound (e.g., crystal violet). As a sorbent for the extraction of MG in sample preparation, MMIPs together with the absorbed analytes could easily be separated from the sample matrix with an external magnet. After elution with methanol/acetic acid (9:1, v/v), MG in the eluent was determined by high-performance liquid chromatography coupled with UV detector with recoveries of 94.0-115%. Results indicated that the as-prepared MMIPs are promising materials for MG analysis in aquatic products. PMID- 26830558 TI - Influence of polysaccharides on wine protein aggregation. AB - Polysaccharides are the major high-molecular weight components of wines. In contrast, proteins occur only in small amounts in wine, but contribute to haze formation. The detailed mechanism of aggregation of these proteins, especially in combination with other wine components, remains unclear. This study demonstrates the different aggregation behavior between a buffer and a model wine system by dynamic light scattering. Arabinogalactan-protein, for example, shows an increased aggregation in the model wine system, while in the buffer system a reducing effect is observed. Thus, we could show the importance to examine the behavior of wine additives under conditions close to reality, instead of simpler buffer systems. Additional experiments on melting points of wine proteins reveal that only some isoforms of thaumatin-like proteins and chitinases are involved in haze formation. We can confirm interactions between polysaccharides and proteins, but none of these polysaccharides is able to prevent haze in wine. PMID- 26830559 TI - Plant polyphenols to enhance the nutritional and sensory properties of chocolates. AB - A relatively unexplored method to enhance the sensory and nutritional properties of chocolate is to use plant polyphenols. In this study, a low cost agricultural waste product - mangosteen (Garcinia mangostana Linn.) pericarp - was added as powder in graded amounts (1%, 2% and 3%w/w) to dark and compound chocolates during the mixing stage and evaluated. The particle size distributions of the chocolates were mostly within 30 MUm and the chocolates displayed a homogeneous morphology. The polyphenols (procyanidins and xanthones) in mangosteen pericarp powder were also stable to simulated chocolate processing. The 3% pericarp powder concentration significantly expanded the bioactive profile and total phenolic content (13% in dark chocolates and 50% in compound chocolates) compared to their plain counterparts without affecting sensory qualities. Such low cost plant polyphenols could enhance the bioactive and flavor profile of chocolates, especially in low cocoa content compound chocolates. PMID- 26830560 TI - Coacervation of beta-conglycinin, glycinin and isoflavones induced by propylene glycol alginate in heated soymilk. AB - This study investigated the propylene glycol alginate (PGA)-induced coacervation of beta-conglycinin (7S), glycinin (11S) and isoflavones in heated soymilk. The addition of 0.9% PGA caused 7S, 11S, daidzein and genistein to coacervate following a 1h incubation period. SDS-PAGE showed that the protein bands corresponding to the 7S alpha', 7S alpha, 7S beta, 11S A3, and 11S acidic subunits and the 11S basic proteins in the soymilk supernatant fraction (SSF) decreased to 37.7 +/- 12.7%, 24.7 +/- 3.9%, 4.9 +/- 1.8%, 8.5 +/- 2.7%, 18.1 +/- 1.8% and 6.0 +/- 1.6%, respectively. In addition, isoflavones including daidzein and genistein were also coacervated from the SSF into the soymilk pellet fraction (SPF) following incubation with 0.9% PGA for 1h. The amounts of daidzein and genistein in the SSF decreased to 8.6 +/- 1.6% and 2.0 +/- 1.0%, respectively. HPLC analysis suggested that daidzein and genistein were bound to the 7S and 11S proteins. These results suggested that daidzein and genistein were co precipitated with the 7S and 11S proteins into the SPF by 0.9% PGA. Our results demonstrated that PGA is a potent coagulant for the coacervation of 7S, 11S, daidzein and genistein. PMID- 26830561 TI - Chemical composition and nutritional evaluation of the seeds of Acacia tortilis (Forssk.) Hayne ssp. raddiana. AB - Chemical composition and nutritional evaluation as well as physicochemical and functional properties of seed flour of Acacia tortilis (Forssk.) Hayne ssp. raddiana were studied. The results indicated that seeds contained 5.30% moisture, 3.99% ash, 9.19% fat, 14.31% fiber, 27.21% protein and 45.30% carbohydrates. Potassium was the predominant element followed by calcium and then phosphorous. Phytic acid, tannins and trypsin inhibitor as antinutrients were detected. The amino acid profile compared well with FAO/WHO recommended pattern except for cystine/methionine, isoleucine, tyrosine/phenylalanine, lysine and threonine. Also, the first limiting amino acid was lysine. Fatty acid composition showed that linoleic acid was the major fatty acid, followed by palmitic, stearic, oleic and arachidic acids. The seed oil showed absorbance in the ultraviolet ranges, thus it can be used as a broad spectrum UV protectant. For physicochemical and functional properties, acacia seeds flour had excellent water holding index, swelling index, foaming capacity and foam stability. PMID- 26830563 TI - Immobilized rennin in TC/SG composite in cheese production. AB - The object of the current study was to develop a new process for continuous Feta type cheese production using a biocatalyst consisting of immobilized rennin on a tubular cellulose/starch gel (TC/SG) composite, which has been proven to be an appropriate carrier for enzyme immobilization. Different methodologies were used in order to prepare four biocatalysts. The most effective was selected for cheese production in a 1L continuous system, providing two economically useful results for the dairy industries: (i) increase of productivity by the continuous coagulation of milk, and (ii) saving of the rennin enzyme expenses of the batch coagulation of milk. The criteria used to choose the appropriate biocatalyst was based on the time of coagulation in successive batches, the concentration of immobilized rennin combined with the filter efficiency and its application in the continuous system. Physicochemical analyses of the cheeses at various stages of the ripening were performed. No significant differences compared to cheeses prepared with the traditional method were found. Aroma compounds were determined by SPME GC-MS. PMID- 26830562 TI - Encapsulation of lactase (beta-galactosidase) into kappa-carrageenan-based hydrogel beads: Impact of environmental conditions on enzyme activity. AB - Encapsulation of enzymes in hydrogel beads may improve their utilization and activity in foods. In this study, the potential of carrageenan hydrogel beads for encapsulating beta-galactosidase was investigated. Hydrogel beads were fabricated by injecting an aqueous solution, containing beta-galactosidase (26 U) and carrageenan (1 wt%), into a hardening solution (5% potassium chloride). Around 63% of the beta-galactosidase was initially encapsulated in the hydrogel beads. Encapsulated beta-galactosidase had a higher activity than that of the free enzyme over a range of pH and thermal conditions, which was attributed to the stabilization of the enzyme structure by K(+) ions within the carrageenan beads. Release of the enzyme from the beads was observed during storage in aqueous solutions, which was attributed to the relatively large pore size of the hydrogel matrix. Our results suggest that carrageenan hydrogel beads may be useful encapsulation systems, but further work is needed to inhibit enzyme leakage. PMID- 26830564 TI - Evaluation of raw soapstone (steatite) as adsorbent of trace elements present in Brazilian spirits. AB - The impact of soapstone (steatite) upon inorganic element contaminant concentrations in alcoholic beverages was investigated. Concentrations of As, Cd, Cu, Ni and Pb levels in 8 Brazilian spirits plus an alcoholic simulant were initially measured, and then measured following each 24h cycle of exposure to raw soapstone cups, for a total of 4 cycles/sample. The results were compared to the levels established by Brazilian and German regulations. The contact between the spirits and the soapstone reduced the Cu content by up to 50.4% and increased the Ni content by up to 622.2%, especially in the first contact cycle. The exposure of spirits to the soapstone exhibits a linear reduction in the Pb content (18.3 54.5%) while As and Cd levels remained unaltered throughout the experiments. In conclusion, crude soapstone in contact with alcoholic solutions acts as an adsorbent of trace elements (Cu and Pb) while releasing Ni. PMID- 26830565 TI - Characterization of milk proteins-lutein complexes and the impact on lutein chemical stability. AB - In this study, the interaction of WPI (whey protein isolate) and SC (sodium caseinate) with hydrophobic lutein was investigated through UV-vis spectroscopy and circular dichroism (CD) as well as fluorescence. The effects on lutein's chemical stability were also examined. The decrease of turbidity of lutein suggested that lutein's aqueous solubility was improved after binding with milk proteins. CD analysis indicated lutein had little impact on the secondary structures of both proteins. Different preparation methods have significant impacts on the binding constant. Fluorescence results indicated that WPI and SC interact with lutein by hydrophobic contacts. Milk proteins have protective effects on lutein against oxidation and decomposition, and SC showed better capability in protecting lutein from oxidation than WPI during 16 days storage. The lutein's chemical stability was increased with increasing of proteins concentration. The results indicated that milk proteins may act as effective carriers for lipophilic nutraceuticals. PMID- 26830566 TI - Novel multiresidue method for determination of pesticides in red wine using gas chromatography-mass spectrometry and solid phase extraction. AB - A new multiresidue method was developed for determination of 25 pesticide residues in red wine by gas chromatography coupled to mass spectrometry with a single run of 23.63 min. Samples were extracted from wine with solid phase extraction using Oasis HLB. Mixture of methanol and water was used for rinsing, while acetonitrile and n-hexane were used as elution solvents. Method was validated according to SANCO/12571/2013 criteria in wide linearity range (limit of quantification - 400 MUg L(-1)). Limits of quantification (LOQ) were well below 10 MUg L(-1) for most pesticides and recoveries at 2*LOQ and 10*LOQ concentration levels were in range 70-120%. Precision, expressed as a relative standard deviation, was always under 14%. The method was applied to 32 red wine samples from Croatia. Pesticides were detected in 30 samples with a total of 15 pesticides found, 7 of which were at a high concentration. PMID- 26830567 TI - High pressure homogenization processing, thermal treatment and milk matrix affect in vitro bioaccessibility of phenolics in apple, grape and orange juice to different extents. AB - The effects of high pressure homogenization processing (HPHP), thermal treatment (TT) and milk matrix (soy, skimmed and whole milk) on the phenolic bioaccessibility and the ABTS scavenging activity of apple, grape and orange juice (AJ, GJ and OJ) were investigated. HPHP and soy milk diminished AJ's total phenolic bioaccessibility 29.3%, 26.3%, respectively, whereas TT and bovine milk hardly affected it. HPHP had little effect on GJ's and OJ's total phenolic bioaccessibility, while TT enhanced them 27.3-33.9%, 19.0-29.2%, respectively, and milk matrix increased them 26.6-31.1%, 13.3-43.4%, respectively. Furthermore, TT (80 degrees C/30 min) and TT (90 degrees C/30 s) presented the similar influences on GJ's and OJ's phenolic bioaccessibility. Skimmed milk showed a better enhancing effect on OJ's total phenolic bioaccessibility than soy and whole milk, but had a similar effect on GJ's as whole milk. These results contribute to promoting the health benefits of fruit juices by optimizing the processing and formulas in the food industry. PMID- 26830568 TI - Impact of water extractable arabinoxylan from rye bran on the frozen steamed bread dough quality. AB - Impact of water extractable arabinoxylan from rye bran on frozen steamed bread dough quality was investigated in terms of the bread characteristics, ice crystallization, yeast activity as well as the gluten molecular weight distribution and glutenin macropolymer content in the present study. Results showed that water extractable arabinoxylan significantly improved bread characteristics during the 60-day frozen storage. Less water was crystallized in the water extractable arabinoxylan dough during storage, which could explain the alleviated yeast activity loss. For all the frozen dough samples, more soluble high molecular weight (Mw ~ 91,000-688,000) and low molecular weight (Mw ~ 91,000 16,000) proteins were derived from glutenin macropolymer depolymerization. Nevertheless, water extractable arabinoxylan dough developed higher glutenin macropolymer content with lowered level of soluble low molecular weight proteins throughout the storage. This study suggested water extractable arabinoxylan from rye bran had great potential to be served as an effective frozen steamed bread dough improver. PMID- 26830569 TI - Effects of pH on protein components of extracted oil bodies from diverse plant seeds and endogenous protease-induced oleosin hydrolysis. AB - Plant seeds are used to extract oil bodies for diverse applications, but oil bodies extracted at different pH values exhibit different properties. Jicama, sunflower, peanut, castor bean, rapeseed, and sesame were selected to examine the effects of pH (6.5-11.0) on the protein components of oil bodies and the oleosin hydrolysis in pH 6.5-extracted oil bodies. In addition to oleosins, many extrinsic proteins (globulins, 2S albumin, and enzymes) were present in pH 6.5 extracted oil bodies. Globulins were mostly removed at pH 8.0, whereas 2S albumins were removed at pH 11.0. At pH 11.0, highly purified oil bodies were obtained from jicama, sunflower, peanut, and sesame, whereas lipase remained in the castor bean oil bodies and many enzymes in the rapeseed oil bodies. Endogenous protease-induced hydrolysis of oleosins occurred in all selected plant seeds. Oleosins with larger sizes were hydrolysed more quickly than oleosins with smaller sizes in each plant seed. PMID- 26830570 TI - Comparison of major taste compounds and antioxidative properties of fruits and flowers of different Sambucus species and interspecific hybrids. AB - Differences in the content of sugars, organic acids, total phenolics and antioxidative activity have been evaluated among three different elderberry species (Sambucus nigra, Sambucus cerulea, Sambucus javanica) and seven interspecific hybrids. The highest content of sugars has been determined in the fruits of JA*CER hybrid and the lowest in fruits of (JA*NI)*cv. Black Beauty hybrid. S. nigra berries contained highest levels of total organic acids. S. nigra and (JA*NI)*CER flower extracts were characterized by 1.3- to 2.8-fold higher content of total sugars compared to other species/hybrids analyzed. Total phenolic content (TPC) in berries ranged from 3687 to 6831 mg GAE per kg FW. The highest TPC has been determined in S. nigra fruits and flowers. The ABTS scavenging activity differed significantly among species and hybrids and ranged from 3.2 to 39.59 mM trolox/kgF W in fruits and 44.87-118.26 mM trolox/kg DW in flowers. PMID- 26830571 TI - Novel characterisation of minor alpha-linolenic acid isomers in linseed oil by gas chromatography and covalent adduct chemical ionisation tandem mass spectrometry. AB - Discrimination between polyunsaturated fatty acid isomers with three double bonds is a great challenge, due to structural similarities and similar polarities. In this study, we report the identification of four minor geometrical isomers of alpha-linolenic acid (ALA) present in linseed oil samples: (9E,12Z,15E)-, (9Z,12Z,15E)-, (9Z,12E,15Z)- and (9E,12Z,15Z)-octadeca-9,12,15-trienoic acids, chromatographically resolved by gas chromatography (GC) using a new and highly polar ionic phase column (SLB-IL111). Gas chromatography-electron ionisation mass spectrometry (GC-EIMS) determined that the four unknown compounds were C18:3 n-3 isomers. The positional 9-12-15 C18:3 configuration was achieved by covalent adduct chemical ionisation tandem mass spectrometry (CACI-MS/MS) while geometrical configuration was established with analytical standards based on relative retention. We hypothesised that these isomers are formed during linseed oil deodorisation and postulate preferred and unfavoured isomerisation pathways of ALA. PMID- 26830572 TI - Effects of buffer additives and thermal processing methods on the solubility of shrimp (Penaeus monodon) proteins and the immunoreactivity of its major allergen. AB - This study examines the potential of two buffer additives (Tween 20 and DTT) to improve the solubility of proteins from shrimp subjected to different heat treatments and the allergenicity of tropomyosin in the extracts. The concentration of soluble proteins extracted by all the buffers from processed shrimp was significantly reduced compared with untreated samples. The concentration of total soluble proteins from heat treated shrimp increased significantly when phosphate buffer containing both surfactant and reducing agent was used as the extraction buffer. However, the concentrations of heat-stable proteins in the buffers were mostly similar. The electrophoretic profile of extracted proteins showed that tropomyosin is very stable under the different heat treatment methods used in this study except for high pressure steaming where the intensity of tropomyosin band was reduced. Competitive inhibition ELISA showed that high pressure steaming reduced the allergenicity of tropomyosin compared with other heat treatments methods. PMID- 26830573 TI - Synthesis of rebaudioside-A by enzymatic transglycosylation of stevioside present in the leaves of Stevia rebaudiana Bertoni. AB - Rebaudioside-A is the second most abundant sweet diterpene glycoside (1-3%) present in the leaves of Stevia rebaudiana Bertoni, and is now being considered as a possible sucrose substitute due to its pleasant organoleptic properties and associated health benefits. In the present study, a novel in situ enzymatic transglycosylation of stevioside has been developed by pre-treating the stevia leaves with cellulase and adding soluble starch as the glucosyl donor. The results confirm that the transglycosylation of stevioside led to an enrichment in the rebaudioside-A content from 4% to 66%. This was further purified by multiple column chromatography to obtain 95% pure rebaudioside-A. The isolated rebaudioside-A showed concentration-dependent alpha-glucosidase inhibitory activity with IC50=35.01 MUg/ml. Thus the study highlights the biotransformation of stevioside present in stevia leaves to rebaudioside-A by a simple, inexpensive and eco-friendly process that has commercial potential. PMID- 26830574 TI - Green extraction of grape skin phenolics by using deep eutectic solvents. AB - Conventional extraction techniques for plant phenolics are usually associated with high organic solvent consumption and long extraction times. In order to establish an environmentally friendly extraction method for grape skin phenolics, deep eutectic solvents (DES) as a green alternative to conventional solvents coupled with highly efficient microwave-assisted and ultrasound-assisted extraction methods (MAE and UAE, respectively) have been considered. Initially, screening of five different DES for proposed extraction was performed and choline chloride-based DES containing oxalic acid as a hydrogen bond donor with 25% of water was selected as the most promising one, resulting in more effective extraction of grape skin phenolic compounds compared to conventional solvents. Additionally, in our study, UAE proved to be the best extraction method with extraction efficiency superior to both MAE and conventional extraction method. The knowledge acquired in this study will contribute to further DES implementation in extraction of biologically active compounds from various plant sources. PMID- 26830575 TI - Fast analysis of curcuminoids from turmeric (Curcuma longa L.) by high performance liquid chromatography using a fused-core column. AB - The recent development of fused-core technology in HPLC columns is enabling faster and highly efficient separations. This technology was evaluated for the development of a fast method for the analysis of main curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) present in extracts of turmeric (Curcuma longa L.). A step-by-step strategy was used to optimize temperature (40 55 degrees C), flow rate (1.0-2.5 mL min(-1)), mobile phase composition and equilibration time (1-5 min). A gradient method was developed using acidified water and acetonitrile combined with high column temperature (55 degrees C) and flow rate (2.5 mL min(-1)). Optimized conditions provided a method for the separation of these three curcuminoids in approximately 1.3 min with a total analysis time (sample-to-sample) of 7 min, including the clean-up and the re equilibration of the column. Evaluation of chromatographic performance revealed excellent intraday and interday reproducibility (>99%), resolution (>2.23), selectivity (>1.12), peak symmetry (1.24-1.42) while presenting low limits of detection (<0.40 mg L(-1)) and quantification (<1.34 mg L(-1)). The robustness of the method was calculated according to the concentration/dilution of the sample and the injection volume. Several combinations of methanol and ethanol with water as sample solvents were evaluated and the best chromatographic results and extraction rate were obtained using 100% methanol. Finally, the developed method was validated with different extracts of turmeric rhizome and products that use turmeric in their formulation. PMID- 26830576 TI - Reconstitution baking tests with defatted wheat flour are suitable for determining the functional effects of lipase-treated wheat lipids. AB - A microscale reconstitution baking test, using wheat flour defatted with 2 propanol at 20 degrees C, was established to determine the functional effects of lipids isolated from lipase-treated wheat dough. Proper selection of solvent and extraction temperature was of major importance to maintain the functionality of defatted flour. Dough and gluten from flour defatted with water-saturated 1 butanol (WSB; extracted at 20 degrees C) and 2-propanol (extracted at 75 degrees C) had inferior extensibility and loaf volume compared to control flour extracted with 2-propanol at 20 degrees C. Quantitation of gluten proteins showed that defatting with WSB (20 degrees C) or 2-propanol (75 degrees C) decreased the gliadin and increased the glutenin content. Possible reasons were thiol-disulfide interchange reactions, caused either by heat (2-propanol, 75 degrees C) or by the solvent WSB, which affected gluten proteins. Confocal laser scanning microscopy showed that regular, interconnected gluten structures were only present in dough from flour defatted with 2-propanol at 20 degrees C. PMID- 26830577 TI - Identification of furan fatty acids in the lipids of common carp (Cyprinus carpio L.). AB - Fatty acid (FA) composition was analyzed in muscle and gonad tissues of marketed common carp (Cyprinus carpio). The extracted lipids were separated into four fractions: polar lipids (PL), diacylglycerols, free fatty acids and triacylglycerols (TAG) using thin layer chromatography. FA content within the lipid fractions was determined by gas chromatography with flame ionization detector (GC/FID). The muscle lipids consisted primarily of TAG (96.9% of total FA), while PL were the major component of both male (67.6%) and female gonad (58.6%) lipids. Polyunsaturated fatty acids predominated in PL of all tissues (52.2-55.8% of total FA); monounsaturated fatty acids were the most abundant FA group in TAG of muscle (51.8%) and female gonads (47.8%) whereas high proportion of furan fatty acids (F-acids) (38.2%) was detected in TAG of male gonads. Eight F-acids were identified by gas chromatography-mass spectrometry (GC/MS) in male gonad samples, including less common 12,15-epoxy-13,14-dimethylnonadeca-12,14 dienoic acid with even-numbered alkyl moiety. PMID- 26830578 TI - Flavonol glycosides in berries of two major subspecies of sea buckthorn (Hippophae rhamnoides L.) and influence of growth sites. AB - Flavonol glycosides of wild sea buckthorn (Hippophae rhamnoides ssp. sinensis) berries from China and cultivated berries (H. rhamnoides ssp. mongolica) from Finland and Canada were identified and quantified. Twenty-six flavonol glycosides were found with isorhamnetin and quercetin as the major aglycones. The contents of flavonol glycosides ranged 23-250 mg/100 g fresh berries and were significantly higher in the berries of ssp. sinensis than in those of ssp. mongolica. Among the cultivars of ssp. mongolica, the berries of 'Oranzhevaya' had the lowest (23 mg/100 g) content, and those of 'Prevoshodnaya' the highest content of flavonol glycosides (80 mg/100 g). Within the ssp. mongolica, the samples from Kittila (Northern Finland) had higher levels of most flavonol glycosides than those from Turku (Southern Finland) and Quebec. Among the ssp. sinensis berries of different growth sites, increasing trends were detected in the contents of most of the compounds as the altitude increased and as the latitude decreased. The wild berries (ssp. sinensis) from Sichuan had remarkably high contents and unique profiles of flavonol glycosides. PMID- 26830579 TI - Effect of pre-treatment on physicochemical and structural properties, and the bioaccessibility of beta-carotene in sweet potato flour. AB - The aim of this research was to evaluate the effect of microwave or steam pre treatment of raw sweet potato on physicochemical and microstructural properties, and the bioaccessibility of beta-carotene in sweet potato flour. This is the first report on using the in vitro digestion model suitable for food, as proposed in a consensus paper, to assess the bioaccessibility of beta-carotene in sweet potato flour. The pre-treatments produced a rearrangement of the flour matrix (starch, protein and non-starch polysaccharides), which was greater by using microwaves (M6) conducting to a greater increase in the phase transition temperatures up to 4.14 degrees C, while the enthalpy presented the higher reduction (4.49 J/g), both parameters in respect to the control. The resistant starch fraction was not modified, with about 3% in all samples. Microwave (M6) and all the steam pre-treatments showed the higher bioaccessibility of beta carotene. This flour can be used in the development of new products with high beta-carotene content. PMID- 26830580 TI - Metallic elements (Ca, Hg, Fe, K, Mg, Mn, Na, Zn) in the fruiting bodies of Boletus badius. AB - The aim of this study was to investigate and compare the levels of eight metallic elements in the fruiting bodies of Bay Bolete (Boletus badius; current name Imleria badia) collected from ten sites in Poland to understand better the value of this popular mushroom as an organic food. Bay Bolete fruiting bodies were collected from the forest area near the towns and villages of Ketrzyn, Poniatowa, Bydgoszcz, Pelplin, Wloclawek, Zuromin, Chelmno, Elk and Wilkow communities, as well as in the Augustow Primeval Forest. Elements such as Ca, Fe, K, Mg, Mn, Na and Zn were analyzed by inductively coupled plasma atomic emission spectroscopy (ICP-OES), and mercury by cold vapor atomic absorption spectrometry (CV-AAS). This made it possible to assess the nutritional value of the mushroom, as well as possible toxicological risks associated with its consumption. The results were subjected to statistical analysis (Kruskal-Wallis test, cluster analysis, principal component analysis). PMID- 26830581 TI - Selective extraction and determination of chlorogenic acid in fruit juices using hydrophilic magnetic imprinted nanoparticles. AB - In this paper, the novel hydrophilic magnetic molecularly imprinted nanoparticles were developed for selective separation and determination of chlorogenic acid in aqueous fruit juices. The polymers were prepared by using amino-functionalized magnetic nanoparticles as carriers, branched polyethyleneimine as functional monomer, and chlorogenic acid as template molecule. Branched polyethyleneimine with abundant active amino groups could react with template sufficiently, and its unique dendritic structure may amplify the number of the imprinted cavities. Meanwhile, it would improve the hydrophilicity of imprinted materials for attaining high extraction efficiency. The resulted polymers exhibit fast kinetics, high adsorption capacity, and favorable selectivity. In addition, the obtained nanoparticles were used as solid-phase extraction sorbents for selective isolation and determination of chlorogenic acid in peach, apple, and grape juices (0.92, 4.21, and 0.75 MUg mL(-1), respectively). PMID- 26830582 TI - An iodine supplementation of tomato fruits coated with an edible film of the iodide-doped chitosan. AB - In general, the risk of numerous thyroid cancers inevitably increases among people with iodine deficiencies. An iodide-doped chitosan (CT-I) solution was prepared for dipping tomatoes to coat the fresh surface with an edible film (1.5 MUm), thereby providing iodine-rich fruits for daily intake. Characterisation of the thin film was conducted by FTIR and SEM. Stability of the CT-I film was studied via water immersion at various time intervals, and no residual iodide leached out due to intrinsic interactions between the cationic amino group of chitosan and iodide ions. Moreover, the iodide supplement exhibited no effect on the antioxidant activity of tomatoes. The iodine content in the film-coated tomato was determined by ICP-OES. The tomato coating with 1.5% (w/v) CT-I contained approximately 0.4 MUg iodide per gram fresh weight. In addition, the freshness and storability of iodine-doped tomatoes were also maintained for shelf life concerns. PMID- 26830583 TI - Functional constituents and antioxidant activities of eight Chinese native goji genotypes. AB - We quantified the levels of polyphenols, carotenoids and polysaccharides in fruits of the eight Chinese native goji genotypes, antioxidant activities of these fruit extracts were also evaluated by DPPH, ABTS and FRAP methods. Quercetin-rhamno-di-hexoside (435-1065 MUg/g) and quercetin-3-O-rutinoside (159 629 MUg/g) were found to be the predominant flavonoids. Chlorogenic acid was the most abundant phenolic acid (113-526 MUg/g), while zeaxanthin (17-9306 MUg/g) was the major carotenoid. The total antioxidant activities (TAA) of the berry extracts were significantly correlated with the total polysaccharide and phenolic contents, but not with total carotenoid (TC) levels. Overall, fruits of the Ningxia goji (Lycium barbarum L.) genotypes, DM (Damaye), NJ1 (Ningji No.1), BH (Baihua) and NH (Ningxiahuangguo) were not only rich in polyphenols, carotenoids and polysaccharides, but had significantly higher TAA than those of the other genotypes, suggesting that they represent an excellent source of antioxidants for human nutrition. PMID- 26830584 TI - In-depth glycoproteomic characterisation of grape berry vacuolar invertase using a combination of mass spectrometry-based approaches. AB - Vacuolar invertase is a key enzyme of sugar metabolism in grape berries. A full characterisation of this highly N-glycosylated protein is required to help understand its biological and biochemical significance in grapes. We have developed a mass spectrometry (MS)-based glycoproteomic approach wherein deglycosylated peptides are analysed by LC-MS/MS, while intact glycopeptides are characterised using a dedicated MS method to determine the attachment sites and micro-heterogeneity. For grape invertase, in parallel with deglycosylated peptides analysis, different enzymatic digestions were performed and glycopeptide detection was improved by enrichment method, nanoLC-MS and oxonium glycan ions. This MS-based glycoproteomic approach demonstrates that vacuolar invertase is glycosylated at all twelve potential N-glycosylation sites. Glycosylation is heterogeneous, with twelve glycoforms identified at six of the sites. The identification of several types of N-glycans is a major result to correlate with the surface and foaming properties of wine, the solubility, allergenicity, and protease resistance of wine proteins. PMID- 26830585 TI - Method development for the determination of calcium, copper, magnesium, manganese, iron, potassium, phosphorus and zinc in different types of breads by microwave induced plasma-atomic emission spectrometry. AB - A novel method was developed for the determination of calcium, magnesium, potassium, iron, copper, zinc, and manganese and phosphorous in various kinds of breads samples sold in Turkey by microwave plasma-atomic emission spectrometry (MIP-AES). Breads were dried at 100 degrees C for one day, ground thoroughly and then digested using nitric acid/hydrogen per oxide (3:1). The analytes in certified reference wheat flour and maize flour samples were determined in the uncertainty limits of the certified values as well as the analytes added to the mixture of ground bread and acid mixture prior to digestion were recovered quantitatively (>90%). Therefore, all determinations were made by linear calibration technique using aqueous standards. The LOD values for Ca, Cu, Fe, K, Mg, Mn, P and Zn were 13.1, 0.28, 4.47, 118, 1.10, 0.41, 7550 and 3.00 ng mL(-1), respectively. No spectral interference was detected at the working wavelengths of the analytes. PMID- 26830586 TI - Determination of synthetic phenolic antioxidants in edible oils using microvial insert large volume injection gas-chromatography. AB - Three synthetic phenolic antioxidants, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and tert-butyl hydroquinone (TBHQ), were determined in different edible vegetable oil samples. The analyses were carried out by gas chromatography-mass spectrometry (GC-MS) using microvial insert large volume injection (LVI). Several parameters affecting this sample introduction step, such as temperatures, times and gas flows, were optimised. Quantification was carried out by the matrix-matched calibration method using carvacrol as internal standard, providing quantification limits between 0.08 and 0.10 ng g(-1), depending on the compound. The three phenolic compounds were detected in several of the samples, BHT being the most frequently found. Recovery assays for oil samples spiked at two concentration levels, 2.5 and 10 ng g(-1), provided recoveries in the 86-115% range. PMID- 26830587 TI - Monitoring the phenolic compounds of Greek extra-virgin olive oils during storage. AB - Extra virgin olive oil (EVOO) samples, of five Greek olive varieties, were stored in dark glass bottles (headspace 0.5%) in a basement without central heating for 24 months. Quantitative variations of the phenolic compounds and their degradation products were monitored over time. The differences observed in the initial total phenolic compounds concentration (ranging between 250.77 and 925.75 mg/kg) were attributed to extraction system, olive variety, and maturity stage. Even after 24 months, the degree of reduction in total phenolic compounds did not exceed 31%. The reduction was more pronounced in dialdehydic forms of oleuropein and ligstroside aglycones (DAFOA and DAFLA), indicating a more active participation in the hydrolysis and oxidation processes of the more polar secoiridoids. The initial total phenolic content was the main factor correlated to the degradation rate of the phenolic compounds. The decrease in secoiridoid derivatives, gave rise to hydroxytyrosol and tyrosol content and to the formation of four oxidized products. PMID- 26830588 TI - Impact of light-exposure on the metabolite balance of transgenic potato tubers with modified glycoalkaloid biosynthesis. AB - Metabolite profiling (liquid chromatography-mass spectrometry (LC-MS) and gas chromatography (GC-MS)) was used to assess the impact of light on the composition of transgenic potato (Solanum tuberosum L. cv. Desiree) with reduced glycoalkaloid content via the down-regulation of the SGT1 gene. Transgenic tubers exhibited an almost complete knock-out of alpha-solanine production and light had little impact on its accumulation. Levels of alpha-chaconine increased significantly in the peel of both the control and transgenic lines when exposed to light, particularly in the transgenic line. Major differences in metabolite profiles existed between outer and inner tuber tissues, and between light and dark-treated tubers. Many of the light-induced changes are explicable in terms of pathways known to be affected by stress responses. The impact of transgenesis on profiles was much less than that of tissue type or light and most differences were explicable in terms of the modification to the glycoalkaloid pathway. PMID- 26830589 TI - Carotenoids, carotenoid esters, and anthocyanins of yellow-, orange-, and red peeled cashew apples (Anacardium occidentale L.). AB - Pigment profiles of yellow-, orange-, and red-peeled cashew (Anacardium occidentale L.) apples were investigated. Among 15 identified carotenoids and carotenoid esters, beta-carotene, and beta-cryptoxanthin palmitate were the most abundant in peels and pulp of all samples. Total carotenoid concentrations in the pulp of yellow- and red-peeled cashew apples were low (0.69-0.73 mg/100g FW) compared to that of orange-peeled samples (2.2mg/100g FW). The color difference between the equally carotenoid-rich yellow and red colored samples indicated the presence of a further non-carotenoid pigment type in red peels. Among four detected anthocyanins, the major anthocyanin was unambiguously identified as 7-O methylcyanidin 3-O-beta-D-galactopyranoside by NMR spectroscopy. Red and yellow peel color was chiefly determined by the presence and absence of anthocyanins, respectively, while the orange appearance of the peel was mainly caused by increased carotenoid concentrations. Thus, orange-peeled fruits represent a rich source of provitamin A (ca. 124 MUg retinol-activity-equivalents/100g pulp, FW). PMID- 26830590 TI - Fish gelatin combined with chitosan coating inhibits myofibril degradation of golden pomfret (Trachinotus blochii) fillet during cold storage. AB - Coating of gelatin and chitosan can improve fish fillet's quality, but the mechanism is not clear. Chitosan/gelatin coatings significantly prevented deterioration of golden pomfret fillet at 4 degrees C. Chitosan with 7.2% gelatin group showed the best effect on preserving the length of myofibril, which remained greater than 15 MUm at day 17 of storage, while for control, chitosan and chitosan combined with 3.6% gelatin group, it was 5.03, 10.04 and 9.02 MUm, respectively. The MALDI-TOF MS result revealed that the coatings slowed down the protein deterioration of fillet. On days 13 and 17, the myosin light chain and myoglobin in control group degraded, while the two proteins still existed in chitosan/gelatin coated groups. Overall, the chitosan with 7.2% gelatin coating had the best effect on preserving fillet's quality during storage. The coating may exert its protective effect via inhibiting myofibril degradation within fillet. PMID- 26830591 TI - Identification of red pepper powder irradiated with different types of radiation using luminescence methods: A comparative study. AB - The purpose of this study was to verify the reliability of photostimulated luminescence (PSL) and thermoluminescence (TL) methods for identifying irradiated foods, described in the European standards EN 13751:2002 and EN 1788:2001, respectively, which were established solely through interlaboratory studies on gamma-irradiated food. Red pepper powder samples irradiated with electron-beams (e-beams), gamma rays and high-energy X-rays were used as model foods. Samples irradiated with each radiation type at ?4 kGy could be correctly identified by the PSL method, whereas samples irradiated at ?0.5 kGy with each radiation type could be correctly recognized by the TL method when e-beams, gamma rays, or high energy X-rays were used as normalization sources. However, different TL intensities were observed for minerals separated from red pepper powder for different irradiation sources, which was confirmed using pure quartz and K feldspar minerals. Further interlaboratory studies are required to verify this phenomenon. PMID- 26830592 TI - Evaluation of non-volatile metabolites in beer stored at high temperature and utility as an accelerated method to predict flavour stability. AB - Flavour stability is vital to the brewing industry as beer is often stored for an extended time under variable conditions. Developing an accelerated model to evaluate brewing techniques that affect flavour stability is an important area of research. Here, we performed metabolomics on non-volatile compounds in beer stored at 37 degrees C between 1 and 14 days for two beer types: an amber ale and an India pale ale. The experiment determined high temperature to influence non-volatile metabolites, including the purine 5-methylthioadenosine (5-MTA). In a second experiment, three brewing techniques were evaluated for improved flavour stability: use of antioxidant crowns, chelation of pro-oxidants, and varying plant content in hops. Sensory analysis determined the hop method was associated with improved flavour stability, and this was consistent with reduced 5-MTA at both regular and high temperature storage. Future studies are warranted to understand the influence of 5-MTA on flavour and aging within different beer types. PMID- 26830593 TI - Low-field NMR determination of water distribution in meat batters with NaCl and polyphosphate addition. AB - The objective was to elucidate the influence of NaCl and polyphosphates in the stage of protein swelling on the water-holding capacity (WHC) of meat batter. The meat batters were formulated with salt in different ways by adding established amounts of only NaCl, only polyphosphates, jointly adding NaCl and polyphosphates, and a control without any salt. An increase (p<0.05) in water retention was found when a combination of NaCl and polyphosphates was used. A high textural parameter was observed in the two treatments with NaCl, but not in the group with only polyphosphate. For the polyphosphate group, T22 was lower (p<0.05) than in the other three before heating; however, after heating, T21 and T22 were both significantly decreased, and a new component emerged, T23, which was significantly lower than the others. For the NaCl treatment, heated or not, T22 was always the highest. It was revealed that NaCl had affected the WHC by increasing the mobility and distribution of water, particularly with polyphosphate, but polyphosphate could not be an equal substitute for NaCl given its resulting lowest textural properties and poor microstructure. By presenting different hydration states in the protein swelling stage, the meat batter qualities were differentiated. PMID- 26830594 TI - Identification of different domains of calpain and calpastatin from chicken blood and their role in post-mortem aging of meat during holding at refrigeration temperatures. AB - The aim of this study was to develop a simple, specific and rapid analytical method for accurate identification of calpain and calpastatin from chicken blood and muscle samples. The method is based on liquid-liquid extraction technique followed by casein Zymography detection. The target compounds were extracted from blood and meat samples by tris buffer, and purified and separated on anion exchange chromatography. It has been observed that buffer (pH 6.7) containing 50 mM tris-base appears to be excellent extractant as activity of analytes was maximum for all samples. The concentrations of MU-, m-calpain and calpastatin detected in the extracts of blood, breast and thigh samples were 0.28-0.55, 1.91 2.05 and 1.38-1.52 Unit/g, respectively. For robustness, the analytical method was applied to determine the activity of calpains (MU and m) in eighty postmortem muscle samples. It has been observed that MU-calpain activity in breast and thigh muscles declined very rapidly at 48 h and 24 h, respectively while activity of m calpain remained stable. Shear force values were also declined with the increase of post-mortem aging showing the presence of ample tenderness of breast and thigh muscles. Finally, it is concluded that the method standardized for the detection of calpain and calpastatin has the potential to be applied to identify post mortem aging of chicken meat samples. PMID- 26830595 TI - In vitro antioxidant and anti-inflammatory properties of Limonium algarvense flowers' infusions and decoctions: A comparison with green tea (Camellia sinensis). AB - This work reports the in vitro antioxidant and anti-inflammatory activities and toxicity of infusions and decoctions of Limonium algarvense flowers, and green tea. The total contents in different phenolic groups and the quantification of individual phenolics by HPLC are also reported. L. algarvense and green tea had similar antioxidant properties, except for hydroxyl radical-scavenging activity, higher on green tea, and iron chelating potential, higher on L. algarvense. The later species also had the uppermost anti-inflammatory potential. Green tea decoction had the highest content of phenolic groups, but the infusion of L. algarvense had higher amounts of salicylic, gallic and coumaric acids. L. algarvense was not toxic, whereas green tea was toxic for S17 cells. Under our experimental conditions, infusions and decoctions of L. algarvense flowers had similar or higher antioxidant and anti-inflammatory properties than green tea, and thus, may be useful for alleviating symptoms associated with oxidative and inflammatory-related diseases. PMID- 26830596 TI - Synthetic musk in seafood products from south Europe using a quick, easy, cheap, effective, rugged and safe extraction method. AB - This study aims at developing a method for the determination of 9 synthetic musk compounds in seafood products by combining the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method and determination by gas chromatography mass spectrometry (GC-EI-MS). Method detection limits (MDL) ranging between 0.001 and 1.94 ng g(-1) were obtained. The linearity is higher than 0.9899 in the range MDL - 100 ng g(-1) with precision below 18% and recoveries between 46% and 120% were obtained. The method was applied to quantify musk compounds in seafood products from the European southwest coast (oysters, mussels, salmon organs, glass eels). Galaxolide and Tonalide exhibited the highest concentration levels ranging between MDL - 96.4 ng g(-1) and MDL - 6.85 ng g(-1), respectively. Contamination levels observed for the two nitro musks (musk xylene and musk ketone) are significantly lower ranging between MDL - 0.6 ng g(-1) and MDL - 0.09 ng g(-1), respectively. Analysis of different organs of salmons showed higher concentrations in liver and gonad than in muscle tissues. PMID- 26830597 TI - A simple and selective method for determination of phthalate biomarkers in vegetable samples by high pressure liquid chromatography-electrospray ionization tandem mass spectrometry. AB - In the present study, solid-phase extraction cartridges including silica reversed phase Isolute C18, polymeric reversed-phase Oasis HLB and mixed-mode anion exchange Oasis MAX, and liquid-liquid extractions with ethyl acetate, n-hexane, dichloromethane and its mixtures were compared for clean-up of phthalate monoesters from vegetable samples. Best recoveries and minimised matrix effects were achieved using ethyl acetate/n-hexane liquid-liquid extraction for these target compounds. A simple and selective method, based on sample preparation by ultrasonic extraction and liquid-liquid extraction clean-up, for the determination of phthalate monoesters in vegetable samples by liquid chromatography/electrospray ionisation-tandem mass spectrometry was developed. The method detection limits for phthalate monoesters ranged from 0.013 to 0.120 ng g(-1). Good linearity (r(2)>0.991) between MQLs and 1000* MQLs was achieved. The intra- and inter-day relative standard deviation values were less than 11.8%. The method was successfully used to determine phthalate monoester metabolites in the vegetable samples. PMID- 26830598 TI - Monitoring changes in whiting (Merlangius merlangus) fillets stored under modified atmosphere packaging by front face fluorescence spectroscopy and instrumental techniques. AB - Quality assessment of whiting (Merlangius merlangus) fillets stored in normal air (control group) and modified atmosphere packaging (MAP1: 50% N2/50% CO2 and MAP2: 80% N2/20% CO2) for up to 15 days at 4 degrees C was performed. The physico chemical [pH, drip loss, moisture content, total volatile basic nitrogen (TVB-N), thiobarbituric acid reactive substances (TBARS) and peroxide value (PV)], textural (i.e., hardness, fragility, gumminess, chewiness, springiness, cohesiveness), and color (i.e., L(*), a(*), b(*)) parameters were determined. Front face fluorescence spectroscopy (FFFS) emission spectra were also scanned on the same samples with excitation set at 290 and 360 nm. The results indicated that MAP treatment, particularly MAP1 had an obvious preservative effect on fish quality by reducing pH value, TBARS and TVB-N contents, and retarding the softening of fish texture compared to control samples. Principal component analysis (PCA) applied to physico-chemical and instrumental data sets showed a clear discrimination of fish samples according to both their storage time and condition. A complete (100%) of correct classification was obtained by the concatenation of spectral, physico-chemical, and instrumental data sets. The results demonstrated that storage under MAP can be recommended to improve quality of whiting fillets, which in turn, can be evaluated by FFFS as a rapid and non destructive technique. PMID- 26830599 TI - Improving quantitative structure-activity relationship models using Artificial Neural Networks trained with dropout. AB - Dropout is an Artificial Neural Network (ANN) training technique that has been shown to improve ANN performance across canonical machine learning (ML) datasets. Quantitative Structure Activity Relationship (QSAR) datasets used to relate chemical structure to biological activity in Ligand-Based Computer-Aided Drug Discovery pose unique challenges for ML techniques, such as heavily biased dataset composition, and relatively large number of descriptors relative to the number of actives. To test the hypothesis that dropout also improves QSAR ANNs, we conduct a benchmark on nine large QSAR datasets. Use of dropout improved both enrichment false positive rate and log-scaled area under the receiver-operating characteristic curve (logAUC) by 22-46 % over conventional ANN implementations. Optimal dropout rates are found to be a function of the signal-to-noise ratio of the descriptor set, and relatively independent of the dataset. Dropout ANNs with 2D and 3D autocorrelation descriptors outperform conventional ANNs as well as optimized fingerprint similarity search methods. PMID- 26830600 TI - Geometry optimization method versus predictive ability in QSPR modeling for ionic liquids. AB - Computational techniques, such as Quantitative Structure-Property Relationship (QSPR) modeling, are very useful in predicting physicochemical properties of various chemicals. Building QSPR models requires calculating molecular descriptors and the proper choice of the geometry optimization method, which will be dedicated to specific structure of tested compounds. Herein, we examine the influence of the ionic liquids' (ILs) geometry optimization methods on the predictive ability of QSPR models by comparing three models. The models were developed based on the same experimental data on density collected for 66 ionic liquids, but with employing molecular descriptors calculated from molecular geometries optimized at three different levels of the theory, namely: (1) semi empirical (PM7), (2) ab initio (HF/6-311+G*) and (3) density functional theory (B3LYP/6-311+G*). The model in which the descriptors were calculated by using ab initio HF/6-311+G* method indicated the best predictivity capabilities ([Formula: see text] = 0.87). However, PM7-based model has comparable values of quality parameters ([Formula: see text] = 0.84). Obtained results indicate that semi empirical methods (faster and less expensive regarding CPU time) can be successfully employed to geometry optimization in QSPR studies for ionic liquids. PMID- 26830601 TI - [In time: vitamin D deficiency: who needs supplementation?]. PMID- 26830602 TI - [Waist circumference as a marker for screening nonalcoholic fatty liver disease in obese adolescents]. AB - OBJECTIVE: To assess the relationship between the degree of waist circumference (WC) and nonalcoholic fatty liver disease (NAFLD) in obese adolescents of both genders, analyzed according to quartiles of WC. METHODS: Cross-sectional study that involved 247 obese adolescents aged 12-19 years. Mean values of the nutritional parameters and serum analyses were compared with the groups using the independent t-test. Pearson correlation coefficient was used to determine the relationship of the parameters studied. Chi-square test for trend was used to determine the relationship between the prevalence of the NAFLD and WC quartile by gender. RESULTS: NAFLD were presented in 60% of the study participants. Obese adolescents in the 3rd and 4th quartiles of WC presented higher prevalence of NAFLD when compared with that in the 1st quartile in both genders. The NAFLD patients had significantly higher values for body weight, BMI (body mass index), BAZ-score (BMI-for-age z-scores), total fat (% and kg), WC, visceral fat, insulin, insulin resistance index (HOMA-IR), aspartate aminotransferase and alanine aminotransferase, when compared with non-NAFLD obese adolescents. CONCLUSIONS: The results presented here suggest that an increase in WC can reliably predict the risk of NAFLD in obese adolescents. This is a low cost and easy-to-use tool that can help in screening in adolescents. PMID- 26830603 TI - Cells and extracellular matrix interplay in cardiac valve disease: because age matters. AB - Cardiovascular aging is a physiological process affecting all components of the heart. Despite the interest and experimental effort lavished on aging of cardiac cells, increasing evidence is pointing at the pivotal role of extracellular matrix (ECM) in cardiac aging. Structural and molecular changes in ECM composition during aging are at the root of significant functional modifications at the level of cardiac valve apparatus. Indeed, calcification or myxomatous degeneration of cardiac valves and their functional impairment can all be explained in light of age-related ECM alterations and the reciprocal interplay between altered ECM and cellular elements populating the leaflet, namely valvular interstitial cells and valvular endothelial cells, is additionally affecting valve function with striking reflexes on the clinical scenario. The initial experimental findings on this argument are underlining the need for a more comprehensive understanding on the biological mechanisms underlying ECM aging and remodeling as potentially constituting a pharmacological therapeutic target or a basis to improve existing prosthetic devices and treatment options. Given the lack of systematic knowledge on this topic, this review will focus on the ECM changes that occur during aging and on their clinical translational relevance and implications in the bedside scenario. PMID- 26830605 TI - Diffusion-weighted magnetic resonance imaging in the depiction of gastric cancer: initial experience. AB - The aim of the study was to explore the feasibility of diffusion-weighted magnetic resonance imaging (DW-MRI) in the depiction of gastric cancer and to investigate the signal characteristics and apparent diffusion coefficient (ADC) of gastric cancer. An institutional review board-approved protocol was developed for this prospective study. DW-MRI was performed on 101 patients with gastric cancer that was detected by gastroscopy biopsy. The optimal number of excitations (NEX) for DW-MRI was determined, and the signal characteristics of gastric cancer on DW-MRI were analyzed. The ADC of gastric cancer was measured by two experienced radiologists independently, and the reproducibility of measurement was investigated by the Bland-Altman analysis. When DW-MRI was used with four NEXs, areas of gastric cancer showed a good contrast and contrast-to-noise ratio. Four kinds of signal characteristics of gastric cancer were observed on DW-MRI: uniformly high signal, inner high signal, and outer low signal (two-layer type), high-low-high signal (three-layer sandwich type), and mixed type. The mean ADC of gastric cancer measured by two observers was (1.18 +/- 0.29) * 10(-3) mm(2)/s and (1.20 +/- 0.31) * 10(-3) mm(2)/s respectively, which showed good agreement with Bland-Altman analysis (95% limits of agreement: -0.16 to +0.19 * 10(-3) mm(2)/s). Gastric cancers have various signal characteristics on DW-MRI and the reproducibility of ADC measurement is satisfactory. DW-MRI is helpful in the depiction of gastric cancer. PMID- 26830606 TI - CT colonography after incomplete optical colonoscopy: bowel preparation quality at same-day vs. deferred examination. AB - PURPOSE: To objectively compare the volume, density, and distribution of luminal fluid for same-day oral-contrast-enhanced CTC following incomplete optical colonoscopy (OC) vs. deferred CTC on a separate day utilizing a dedicated CTC bowel preparation. METHODS: HIPAA-compliant, IRB-approved retrospective study compared 103 same-day CTC studies after incomplete OC (utilizing 30 mL oral diatrizoate) against 151 CTC examinations performed on a separate day after failed OC using a dedicated CTC bowel preparation (oral magnesium citrate/dilute barium/diatrizoate the evening before). A subgroup of 15 patients who had both same-day CTC and separate-day routine CTC was also identified and underwent separate analysis. CTC exams were analyzed for opacified fluid distribution within the GI tract, as well as density and volume. Data were analyzed utilizing Kruskal-Wallis and Wilcoxon Signed Rank tests. RESULTS: Opacified luminal fluid extended to the rectum in 56% (58/103) of same-day CTC vs. 100% (151/151) of deferred separate-day CTC (p < 0.0001). For same-day CTC, contrast failed to reach the colon in 11% (11/103) and failed to reach the left colon in 26% (27/103). Volumetric colonic fluid segmentation for fluid analysis (successful in 80 same-day and 147 separate-day cases) showed significantly more fluid in the same-day cohort (mean, 227 vs. 166 mL; p < 0.0001); the actual difference is underestimated due to excluded cases. Mean colonic fluid attenuation was significantly lower in the same-day cohort (545 vs. 735 HU; p < 0.0001). Similar findings were identified in the smaller cohort with direct intra-patient CTC comparison. CONCLUSIONS: Dedicated CTC bowel preparation on a separate day following incomplete OC results in a much higher quality examination compared with same-day CTC. PMID- 26830607 TI - Neuroendocrine carcinoma of the stomach: clinical features and CT findings. AB - PURPOSE: The purpose of the study is to investigate the computed tomographic characteristic and clinical findings of gastric neuroendocrine carcinoma (G-NEC) to increase awareness of this disease. METHODS: Twenty-two patients with a diagnosis of G-NEC were identified through the PACS of our hospital from August 2010 to November 2014. The clinical data, computed tomography (CT) features, and pathology records were analyzed. RESULTS: Among the 22 patients, 21 were male (95.45%), and 1 was female (4.55%). The mean age was 63.5 years old. Positive rates of neuroendocrine markers were 77.28% for chromogranin A staining, 86.36% for synaptophysin staining. All cases were single lesions including 16 (72.73%) in the gastric fundus, 3 (13.64%) in the gastric body and 1 (4.55%) in the gastric angle. Additionally 2 (9.09%) were found in the gastric antrum. Gastric wall was local thickening in 15 cases, and mass formation in 7 cases, with the stenosis and deformation of the adjacent gastric cavity. The long-axis diameter of the lesions ranged from 1.2 to7.4 cm (mean diameter, 2.47 cm), and the long axis diameter was <2 cm in 12 case, 2-7.4 cm in 10 cases. The radiodensity values of the lesions were homogeneous density in 15 cases ranging from 22 to 47 HU (mean 34 HU). An ulcer with an irregular base and slightly raised borders located in the stomach was seen in 19 cases. The CT images showed homogeneous enhancement in 15 cases and heterogeneous enhancement in 7 cases. Obvious enhancement was seen in two cases, moderate enhancement was seen in sixteen cases, and mildly enhancement was seen in four cases. The peak value occurred in the arterial phase in 5 cases and the peak value was seen in 17 cases in the portal phase. Eleven lesions invaded the gastric serosa, and lymphatic metastasis was observed in 21 cases, 8 of which were combined with liver metastasis. CT images revealed 2 cases of the liver metastasis had obvious enhancement. CONCLUSION: The CT features regarding location, incidence rates of ulcer and enhancement pattern described in our findings are common in all malignant gastric tumors. Therefore, the diagnosis of G-NEC must be confirmed with pathological test. PMID- 26830608 TI - Prevalence of benign focal liver lesions: ultrasound investigation of 45,319 hospital patients. AB - PURPOSE: The aim of the study was to determine the sonographic prevalence of benign focal liver lesions on the basis of a population of hospital patients. METHODS: The ultrasound results in a population of (n = 45,319) hospital patients over a period of 10 years were examined retrospectively and evaluated for the diagnosis of benign focal liver lesions [hepatic cysts, hepatic hemangioma, focal nodular hyperplasia (FNH), hepatic adenoma, and focal fatty sparing]. Results that were incomplete or ambiguous were excluded from this study. RESULTS: At least one of the lesions to be investigated was diagnosed in 15.1% (n = 6839) of the patients of the total population. The most commonly recorded lesion, with a total prevalence of 6.3% (n = 2839), was focal fatty sparing, followed by hepatic cysts with 5.8% (n = 2631). The prevalence of hepatic hemangioma was 3.3% (n = 1640), while that of FNH was 0.2% (n = 81) and that of hepatic adenoma was 0.04% (n = 19). An association between the occurrence of benign focal liver lesions and age was observed. CONCLUSIONS: The calculated prevalence of benign focal liver lesions shows that on the fortuitous discovery of space-occupying lesions of the liver, first consideration should be given to focal fatty sparing, simple hepatic cysts and hemangiomas. The finding of a FNH or an adenoma is rarely a random discovery. PMID- 26830609 TI - Prognostic significance of parameters from pretreatment (18)F-FDG PET in hepatocellular carcinoma: a meta-analysis. AB - PURPOSE: The prognostic value of (18)F-deoxyglucose positron emission tomography ((18)F-FDG PET) on hepatocellular carcinoma (HCC) remains inconclusive. This study aims to investigate the prognostic role of pretreatment (18)F-FDG PET on HCC patients by meta-analysis. METHODS: PubMed, Embase, Cochrane library, and Wanfang databases were searched until June 2015. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were synthesized by Stata 10.0, and the combined results were used as effective values. RESULTS: Twenty-two studies containing a total of 1721 patients were identified. According to random-effect model, meta-analysis results showed that high Tumor SUV/Liver SUV (Tsuv/Lsuv) ratio was significantly associated with poorer overall survival (OS) (HR = 2.04; 95% CI 1.50-2.79; P = 0.000) and poorer disease-free survival (HR = 7.17; 95% CI 3.58-14.36; P = 0.000); and high Tumor SUV (Tsuv) value was also correlated with poor OS (HR = 1.53; 95% CI 1.26-1.87; P = 0.000). Meanwhile, subgroup analysis results showed that the significant association above was not altered by study sample size, parameter cutoff value, analytic method, and follow-up period, but there was no significant association between Tsuv/Lsuv ratio and OS in patients who underwent resection (HR = 1.71; 95% CI 1.00-2.92; P = 0.052). CONCLUSIONS: Both high Tsuv/Lsuv ratio and high Tsuv value are associated with poor prognosis in HCC patients. Therefore, pretreatment (18)F-FDG PET is a useful tool in predicting the prognosis of HCC patients. More studies with explicit treatment modalities are required to investigate the prognostic value of pretreatment (18)F FDG PET on HCC patients. PMID- 26830610 TI - Non-invasive prediction of portal pressures using CT and MRI in chronic liver disease. AB - PURPOSE: To assess the diagnostic value of a fast scoring system based on non invasive cross-sectional imaging to predict portal hypertension (PH) in patients with liver disease. METHODS: In this retrospective study, we included patients who underwent contrast-enhanced CT or MRI within 3 months of hepatic venous pressure gradient (HVPG) measurements. Two independent observers provided an imaging-based scoring system (max of 9): number of variceal sites, volume of ascites, and spleen size. ROC analysis was performed to predict the presence of PH (HVPG >= 5 mmHg) and clinically significant PH (HVPG >= 10 mmHg). RESULTS: Our cohort consists of 143 patients with mean HVPG of 13.1 +/- 2.0 mmHg. Mean PH scores from the two observers were 3.9 +/- 2.7 and 3.2 +/- 2.5. There was a significant correlation between PH score and HVPG (r = 0.58, p < 0.001 for both observers) with high inter-observer agreement (kappa 0.71). AUCs of 0.78-0.76 and 0.83-0.81 were observed for diagnosing HVPG >= 5 mmHg and HVPG >= 10 mmHg, respectively, for observers 1 and 2. CONCLUSIONS: We have developed a fast PH imaging-based composite score, which could be used for non-invasive detection of clinically significant PH. PMID- 26830612 TI - Diffusion-weighted imaging (DWI) of the liver in assessing chronic liver disease: effects of the presence and the degree of ascites on ADC values. AB - PURPOSE: The aim of this study was to determine the correlation between the liver and spleen apparent diffusion coefficient (ADC) values of patients with chronic liver disease and the presence and the degree of ascites. MATERIALS AND METHOD: In this retrospective study, we assessed 107 patients with chronic liver disease and 39 control subjects who underwent upper abdominal MR imaging including echo planar diffusion-weighted imaging (DWI). Among the 107 cirrhotic patients, 56 were classified as group 1, 25 as group 2, and 26 as group 3 according to the absence, the presence of minimal, and the presence of massive ascites, respectively. The scores of model for end-stage liver disease (MELD) were matched between groups as the standard reference. The liver ADC, spleen ADC, and normalized liver ADC values were compared between the control group and patients' groups. RESULTS: Patients with massive ascites had significantly higher MELD score compared with the other groups. The MELD score was also significantly higher in patient groups than in control group. The liver and normalized liver ADCs of patients' groups were significantly lower than that of the control group. With some overlap among groups, the measured ADC values decreased as the amount of the ascites increased, and these relationships were statistically significant. Furthermore, compared to control group, patients with massive ascites had significantly higher spleen ADCs. CONCLUSION: Our results indicate that the ADC value of the liver and spleen correlates with the presence and the degree of ascites in patients with chronic liver disease, and merits further study. PMID- 26830611 TI - Inter-observer agreement on the assessment of relative liver lesion signal intensity on hepatobiliary phase imaging with gadoxetate (Gd-EOB-DTPA). AB - PURPOSE: The purpose of the study was to assess the inter-observer agreement on the qualitative and quantitative evaluation of relative signal intensity of liver lesions on delayed hepatobiliary phase (HBP) MRI with gadoxetate (Gd-EOB-DTPA). METHODS: 105 patients with liver lesions, who had delayed HPB MRI using gadoxetate were reviewed retrospectively. For each patient, four readers (two fellows in training and two attending radiologists) qualitatively assessed the relative SI of the largest representative lesion on a five point scale, and quantitatively measured the relative SI of the lesion to adjacent liver parenchyma using region of interests (ROI). Intra-class correlation (ICC) and kappa statistics with quadratic weights (k) analysis, and maximally selected rank statistic were performed. RESULTS: Substantial agreement between fellows (k = 0.719; ICC = 0.705) and almost perfect agreement between attending radiologists (k = 0.853; ICC = 0.849) were found for both qualitative and quantitative assessments of relative SI on delayed HPB imaging. A cut-off ratio to differentiate between hypointense and iso- to hyperintense lesions by ROI was calculated to be 0.90. CONCLUSION: Inter-observer agreement of liver lesion relative SI on delayed HBP imaging is high and may improve with radiologist experience. A cut-off ratio of relative SI at 0.90 may be useful to quantitatively distinguish hypointense from iso- to hyperintense liver lesions. PMID- 26830613 TI - Hypovascular hepatic nodules at gadoxetic acid-enhanced MRI: whole-lesion hepatobiliary phase histogram metrics for prediction of progression to arterial enhancing hepatocellular carcinoma. AB - PURPOSE: To explore whole-lesion histogram analysis of the hepatobiliary phase (HBP) defect in indeterminate hypovascular liver lesions for predicting progression to arterial-enhancing hepatocellular carcinoma (HCC). METHODS: Twenty patients undergoing gadoxetic acid-enhanced MRI for HCC screening with 12 degrees and 25 degrees flip angle (FA) HBP acquisitions demonstrating an indeterminate lesion showing HBP hypointensity but no arterial enhancement were included. Volumes-of-interest were placed on HBP defects, from which histogram metrics were obtained. Associations between these metrics and progression to arterial enhancing HCC on follow-up imaging were investigated. Lesions were also assessed for the presence of a signal abnormality on conventional sequences. RESULTS: 40% of lesions progressed to arterial-enhancing HCC; 60% were stable at >=6 months follow-up. Neither T2-hyperintensity increased diffusion signal nor portal/equilibrium phase washout was different between progressing and nonprogressing lesions (p = 1.0). Among direct signal intensity-based measures (overall mean; mean of bottom 10th, 10-25th, and 25-50th percentiles), area-under the-curve (AUC) for prediction of progression to arterial-enhancing HCC was consistently higher at 25 degrees (range 0.619-0.657) than at 12 degrees (range 0.512-0.548). However, at both FAs, the four measures with highest AUC were measures related to lesion texture and heterogeneity [standard deviation (SD), coefficient of variation (CV), skewness, and entropy], having AUC of 0.655-0.750 at 12 degrees and 0.686-0.800 at 25. The metric with highest AUC at 12 degrees was SD (AUC = 0.750) and at 25 degrees was CV (AUC = 0.800). CONCLUSION: Whole lesion histogram HBP measures of indeterminate hypovascular liver lesions may help predict progression to arterial-enhancing HCC by reflecting greater lesion heterogeneity, particularly at higher FA. Larger studies are therefore warranted. PMID- 26830614 TI - Comparative 13-year meta-analysis of the sensitivity and positive predictive value of ultrasound, CT, and MRI for detecting hepatocellular carcinoma. AB - PURPOSE: To compare the per-lesion sensitivity and positive predictive value (PPV) of ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) for the diagnosis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The meta-analysis of sensitivity included 242 studies (15,713 patients); 116 studies (7492 patients) allowed calculation of PPV. Pooled per-lesion sensitivity and PPV for HCC detection were compared using empirical Bayes estimates of a beta-binomial model. RESULTS: The pooled per-lesion sensitivity and PPV of contrast-enhanced CT (73.6%, 85.8%) and gadolinium-enhanced MRI (77.5%, 83.6%) are not significantly different (P = 0.08, P = 0.2). However, if the hepatobiliary agent gadoxetate is used, MRI has significantly higher pooled per-lesion sensitivity and PPV (85.6%, 94.2%) than CT (P < 0.0001) or than MRI with other agents (P < 0.0001). Non-contrast-enhanced US has the lowest overall sensitivity and PPV (59.3%, 77.4%). Pooled per-lesion sensitivity and PPV of contrast-enhanced US (84.4%, 89.3%) are relatively high, but no contrast-enhanced US study used the most rigorous reference standards. CONCLUSION: MRI utilizing the hepatobiliary agent gadoxetate has the highest overall sensitivity and PPV, and may be the single optimal method for diagnosis of HCC. Non-contrast-enhanced US has the lowest sensitivity and PPV. More rigorous reference standards are needed to compare the performance of contrast-enhanced US with CT and MRI. Differences in sensitivity and PPV between CT and conventional gadolinium enhanced MRI are not statistically significant overall. PMID- 26830615 TI - Risk of contrast-induced nephropathy for patients receiving intravenous vs. intra arterial iodixanol administration. AB - PURPOSE: To compare the incidence of contrast-induced nephropathy (CIN) for intravenous vs. intra-arterial administration of iodixanol, compared to non administration. METHODS: We retrospectively identified 650 patients who had intravenous iodixanol-enhanced CT, 695 with intra-arterial iodixanol cardiac catheterization, 651 with unenhanced CT, and those who also had baseline and follow-up serum creatinine within 5 days of the exam. From the medical records, we recorded the gender, age, baseline and follow-up serum creatinine/eGFR; underlying renal injury risk factors; indication for imaging; contrast material administration volume, concentration, and route of administration; and use of pre imaging prophylactic measures for CIN. Univariate and multivariate models were used to determine predictors of CIN. RESULTS: Baseline eGFR was lower for patients undergoing unenhanced CT than intravenous or intra-arterial patients (68 vs. 74.6 and 72.2, respectively, p < 0.01) and not different between intravenous and intra-arterial patients (p = 0.735). Simple logistic regression did not show a difference in the rate of CIN in patients who received intravenous vs. intra arterial iodixanol (28 of 650, 4%, vs. 28 of 695, 4%, respectively, p = 0.798), nor a higher rate of CIN than seen with unenhanced CT (45 of 651, 7%, p = 0.99 and p = 0.98 by one-sided t test). Multivariate regression modeling showed that only elevated baseline creatinine or decreased eGFR and low hematocrit/hemoglobin were associated with CIN incidence (odds ratio 1.28 and 2.5; p < 0.023 and <0.006, respectively). CONCLUSIONS: Elevation in serum creatinine due to intravenous and intra-arterial iodixanol administration is infrequent and is not more common than after unenhanced CT scans. PMID- 26830616 TI - Readout-segmented echo-planar imaging in diffusion-weighted imaging of the kidney: comparison with single-shot echo-planar imaging in image quality. AB - OBJECTIVE: The purpose of this study was to compare the image quality of readout segmented echo-planar imaging (RS-EPI) and that of standard single-shot echo planar imaging (SS-EPI) in the kidney in a rat model. MATERIALS AND METHODS: Twelve Wistar rats undergoing MRI examinations were imaged with two diffusion weighted (DW) imaging protocols: a standard SS-EPI and a new RS-EPI protocol, both with a 1.0 * 1.0 * 3.0 mm voxel. The two groups of diffusion-weighted images were independently scored on geometric distortion, image blurring, signal dropout, and the overall image quality by two radiologists. Signal-to-noise ratio (SNR) and apparent diffusion coefficient (ADC) were measured on both sequences. Inter-rater agreement (IRA) was evaluated by Fleiss kappa (kappa) and inter-class correlation coefficient (ICC) statistics. Comparisons of image qualities were made by Wilcoxon signed-rank test and paired-sample t test. RESULTS: Both RS-EPI and SS-EPI had good IRAs in scoring image qualities (kappa = 0.607-0.833) and measuring renal ADCs (ICC = 0.828-0.945). Compared to SS-EPI, RS-EPI produced less geometric distortion (median score 1.5 versus 2.5, p < 0.0001), less image blurring (1.75 versus 2.0, p = 0.0003), less signal dropout (1.0 versus 3.0, p = 0.0001), and a lower score in overall image artifacts (4.25 versus 7.25; p < 0.0001). RS-EPI had higher SNR of renal DW images than SS-EPI (p < 0.001). The intra-variability of ADCs in cortex, outer medulla, and inner medulla ranged from 9.6% to 11.1% (Pearson correlation coefficient rho = 0.675-0.729; p < 0.001) between the two protocols. CONCLUSION: We showed that for DWI of the kidney at 1.0 * 1.0 * 3.0 mm(3) voxel sizes, the new protocol provided better image quality than standard SS-EPI protocol. PMID- 26830617 TI - PET/CT imaging of renal cell carcinoma with (18)F-VM4-037: a phase II pilot study. AB - BACKGROUND: Carbonic anhydrase IX (CA-IX) is a potential imaging biomarker of clear cell renal cell carcinoma (ccRCC). Here, we report the results of a phase II clinical trial of a small molecule radiotracer targeting CA-IX ((18)F-VM4-037) in ccRCC. METHODS: Between October 2012 and May 2013, 11 patients with kidney masses underwent (18)F-VM4-037 PET/CT prior to surgery. Dynamic imaging was performed for the first 45 min post injection and whole-body imaging was obtained at 60 min post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging. RESULTS: All patients tolerated the radiotracer well with no adverse events. Ten of the 11 patients had histologically confirmed malignancy. One patient had a Bosniak Type 3 cyst with no tumor found at surgery. Two patients had extrarenal disease and 9 had tumors only in the kidney. Primary ccRCC lesions were difficult to visualize on PET alone due to high uptake of the tracer in the adjacent normal kidney parenchyma, however when viewed in conjunction with CT, the tumors were easily localized. Metastatic lesions were clearly visible on PET. Mean SUV for primary kidney lesions was 2.55 in all patients; in patients with histologically confirmed ccRCC, the mean SUV was 3.16. The time-activity curves (TAC) are consistent with reversible ligand binding with peak activity concentration at 8 min post injection followed by washout. Distribution Volume Ratio (DVR) of the lesions was measured using the Logan graphical analysis method. The mean DVR value across the 9 kidney lesions was 5.2 +/- 2.8, (range 0.68-10.34). CONCLUSION: 18F-VM4-037 is a well-tolerated PET agent that allows same day imaging of CA-IX expression. The agent demonstrated moderate signal uptake in primary tumors and excellent visualization of CA-IX positive metastases. While the evaluation of primary ccRCC lesions is challenging due to high background activity in the normal kidney parenchyma, 18F-VM4-037 may be most useful in the evaluation of metastatic ccRCC lesions. PMID- 26830618 TI - Optimization of non-contrast-enhanced MR angiography of the renal artery with three-dimensional balanced steady-state free-precession and time-spatial labeling inversion pulse (time-SLIP) at 3T MRI, in relation to age and blood velocity. AB - PURPOSE: To determine the optimal inversion time (TI) value of three-dimensional (3D) balanced steady-state free-precession time-spatial labeling inversion pulse (time-SLIP) technique for visualization of the renal artery at 3T MRI, and to assess whether the optimal TI is affected by the subject's age and blood velocity. MATERIALS AND METHODS: Forty-two healthy volunteers (range 20-67 years) were enrolled in the study and subjected to non-contrast-enhanced renal MR angiography. Five different TI values (1200, 1400, 1600, 1800, and 2000 ms) were selected for evaluation. For quantitative evaluation, the relative signal intensity (SI) of the main renal artery was compared with that of the renal medulla (Vessel-to-Kidney ratio; VKR). Blood velocity of the abdominal aorta was measured using 2D phase contrast technique. For qualitative evaluation, two radiologists scored the depiction of the renal pelvis and the quality of visualization of the renal artery. RESULTS: VKR is the highest at TI = 1600 ms. A strong negative correlation between age and blood velocity was demonstrated. Regarding the qualitative evaluation, the overall image scores of renal arteries were the highest at a TI = 1800 ms for both readers. The optimal TI values in subjects below 50 years of age were 1600 and 1800 ms, whereas in subjects above 50 years of age, the optimal TI value was 1800 ms. CONCLUSION: The optimal TI value for the visualization of renal arteries using time-SLIP technique at 3T MRI was 1800 ms. Subjects' age affected optimal TI and this is likely due to differences in the blood velocity of the abdominal aorta. PMID- 26830619 TI - MR assessment of myometrial invasion in women with endometrial cancer: discrepancy between T2-weighted imaging and contrast-enhanced T1-weighted imaging. AB - PURPOSE: The purpose of the study was to investigate how frequently discrepant imaging findings are encountered between T2-weighted imaging and contrast enhanced T1-weighted imaging in the preoperative magnetic resonance (MR) assessment of myometrial invasion in women with endometrial cancer. METHODS: Seventy-one consecutive women (mean age, 59 years; age range 35-86 years) with endometrial cancer who underwent preoperative MR imaging were included in this single-institution, retrospective study. Depth of myometrial invasion was separately assessed on T2-weighted imaging and contrast-enhanced T1-weighted imaging, and the assessment was considered discrepant, when the two imaging sequences did not match each other. The image analysis also included potential pitfalls responsible for discrepant imaging findings, including the absence of the junctional zone, disruption of the junctional zone, extension to the uterine cornu, presence of leiomyoma and presence of adenomyosis. The results were correlated with histopathologic findings. RESULTS: Of the 71 women, 19 (26.8%) showed discrepant imaging findings between T2-weighted imaging and contrast enhanced T1-weighted imaging. Histopathologic findings revealed that contrast enhanced T1-weighted imaging correctly depicted endometrial cancers in all women with discrepant MR imaging findings. Among the analyzed potential pitfalls, only disruption of the junctional zone showed a significant difference between women with concordant MR imaging findings (29.5%, 13/44) and women with discordant MR imaging findings (93.8%, 15/16) (p = 0.000). CONCLUSION: In the preoperative MR assessment of myometrial invasion in women with endometrial cancer, discrepant imaging findings between T2-weighted imaging and contrast-enhanced T1-weighted imaging are frequently encountered, especially when the junctional zone is disrupted. PMID- 26830620 TI - Multimodality approach for imaging of non-traumatic acute abdominal emergencies. AB - "Acute abdomen" includes spectrum of medical and surgical conditions ranging from a less severe to life-threatening conditions in a patient presenting with severe abdominal pain that develops over a period of hours. Accurate and rapid diagnosis of these conditions helps in reducing related complications. Clinical assessment is often difficult due to availability of over-the-counter analgesics, leading to less specific physical findings. The key clinical decision is to determine whether surgical intervention is required. Laboratory and conventional radiographic findings are often non-specific. Thus, cross-sectional imaging plays a pivotal role for helping direct management of acute abdomen. Computed tomography is the primary imaging modality used for these cases due to fast image acquisition, although US is more specific for conditions such as acute cholecystitis. Magnetic resonance imaging or ultrasound is very helpful in patients who are particularly sensitive to radiation exposure, such as pregnant women and pediatric patients. In addition, MRI is an excellent problem-solving modality in certain conditions such as assessment for choledocholithiasis in patients with right upper quadrant pain. In this review, we discuss a multimodality approach for the usual causes of non-traumatic acute abdomen including acute appendicitis, diverticulitis, cholecystitis, and small bowel obstruction. A brief review of other relatively less frequent but important causes of acute abdomen, such as perforated viscus and bowel ischemia, is also included. PMID- 26830621 TI - MRI of common and uncommon pathologies involving the periportal space: a pictorial essay. AB - Imaging detection and differential diagnoses of pathology involving the periportal space can be challenging. MRI is a useful technique for assessment of the periportal space since it readily distinguishes normal and abnormal vascular and biliary anatomy, and the excellent soft tissue discrimination allows for detection of subtle lesions. This pictorial essay describes the anatomy of the periportal space and illustrates the MRI appearance of a variety of pathologies that can affect this region. PMID- 26830622 TI - Regenerative liver surgeries: the alphabet soup of emerging techniques. AB - New surgical procedures taking advantage of the regenerative abilities of the liver are being introduced as potential curative therapies to these patients either to provide auxiliary support while the native liver recovers or undergoes hypertrophy. For patients with hepatocellular carcinoma outside of the Milan criteria or bilobar colorectal metastases liver transplantation is not an option. Fulminant hepatic failure can be treated but requires life-long immunosuppression. These complex surgical procedures require high quality and directed imaging. PMID- 26830623 TI - Multidetector CT imaging of bariatric surgical complications: a pictorial review. AB - The prevalence of obesity is increasing, along with the number of bariatric surgical procedures performed to treat obesity. Laparoscopic sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and laparoscopic gastric banding (GB) comprise the vast majority of procedures with SG now the dominant procedure in the USA. Although multidetector computed tomography (MDCT) is not always the examination of choice for a particular suspected complication, many of these patients present with non-specific abdominal symptoms and undergo MDCT evaluation as an initial diagnostic test. This pictorial essay will review and discuss the normal post-surgical bariatric appearance on MDCT, and the appearance of common and uncommon complications associated with the common bariatric procedures on MDCT with correlative imaging. SG complications include leak/abscess, hemorrhage, splenic injury, and portomesenteric thrombosis. RYGB complications include leak/abscess, gastrogastric fistula, small bowel obstruction, internal hernia, and intussusception. Although GB is waning in popularity, radiologists continue to see the legacy of these patients and complications include gastric prolapse, band erosion, and port/tubing mechanical failures. Awareness of the characteristic findings of bariatric complications on MDCT is critical, allowing for earlier recognition and prompt intervention. PMID- 26830624 TI - Technical advancements and protocol optimization of diffusion-weighted imaging (DWI) in liver. AB - An area of rapid advancement in abdominal MRI is diffusion-weighted imaging (DWI). By measuring diffusion properties of water molecules, DWI is capable of non-invasively probing tissue properties and physiology at cellular and macromolecular level. The integration of DWI as part of abdominal MRI exam allows better lesion characterization and therefore more accurate initial diagnosis and treatment monitoring. One of the most technical challenging, but also most useful abdominal DWI applications is in liver and therefore requires special attention and careful optimization. In this article, the latest technical developments of DWI and its liver applications are reviewed with the explanations of the technical principles, recommendations of the imaging parameters, and examples of clinical applications. More advanced DWI techniques, including Intra-Voxel Incoherent Motion (IVIM) diffusion imaging, anomalous diffusion imaging, and Diffusion Kurtosis Imaging (DKI) are discussed. PMID- 26830625 TI - The perianal "horseshoe". PMID- 26830627 TI - 15d-Prostaglandin J2 induced reactive oxygen species-mediated apoptosis during experimental visceral leishmaniasis. AB - 15-Deoxy-delta (12,14)-prostaglandin J2 (15d-PgJ2) is a potent bioactive lipid mediator, known to possess several roles in cell regulation and differentiation along with antimicrobial efficacy against different bacterial and viral infections. In the present study, we investigated the therapeutic efficacy and mechanism of action of 15d-PgJ2 in vitro in Leishmania donovani promastigotes and infected J774 macrophages, and in vivo in Balb/c mice/golden hamster model of experimental visceral leishmaniasis. 15d-PgJ2 effectively killed L. donovani promastigotes and amastigotes in vitro with IC50 of 104.6 and 80.09 nM, respectively. At 2 mg/kg (mice) and 4 mg/kg (hamster) doses, 15d-PgJ2 decreased >90 % spleen and liver parasite burden. It significantly reduced interleukin (IL) 10 and transforming growth factor (TGF)-beta synthesis in infected macrophages and splenocytes. 15d-PgJ2 induced reactive oxygen species (ROS)-dependent apoptosis of promastigotes by triggering phosphatidyl serine externalization, mitochondrial membrane damage and inducing caspase-like activity. In vitro drug interaction studies revealed an indifference to the synergistic association of 15d-PgJ2 with Miltefosine and Amphotericin-B (Amp-B). Moreover, when combined with sub-curative doses of Miltefosine and Amphotericin-B, 15d-PgJ2 resulted in >95 % parasite removal. Our results suggested that 15d-PgJ2 induces mitochondria dependent apoptosis of L. donovani and is a good therapeutic candidate for adjunct therapy against experimental visceral leishmaniasis. KEY MESSAGE: 15d PgJ2 effectively eliminated both promastigotes and amastigotes form of L. donovani. 15d-PgJ2 decreased parasite burden from infected mice and hamsters with reduced Th2 cytokines. 15d-PgJ2 induced ROS-mediated mitochondrial apoptosis of L. donovani promastigotes. 15d-PgJ2 is a good therapeutic candidate for adjunct therapy with Miltefosine and Amp-B. PMID- 26830629 TI - Engineering of frustration in colloidal artificial ices realized on microfeatured grooved lattices. AB - Artificial spin ice systems, namely lattices of interacting single domain ferromagnetic islands, have been used to date as microscopic models of frustration induced by lattice topology, allowing for the direct visualization of spin arrangements and textures. However, the engineering of frustrated ice states in which individual spins can be manipulated in situ and the real-time observation of their collective dynamics remain both challenging tasks. Inspired by recent theoretical advances, here we realize a colloidal version of an artificial spin ice system using interacting polarizable particles confined to lattices of bistable gravitational traps. We show quantitatively that ice selection rules emerge in this frustrated soft matter system by tuning the strength of the pair interactions between the microscopic units. Via independent control of particle positioning and dipolar coupling, we introduce monopole-like defects and strings and use loops with defined chirality as an elementary unit to store binary information. PMID- 26830628 TI - Low ambient oxygen prevents atherosclerosis. AB - Large population studies have shown that living at higher altitudes, which lowers ambient oxygen exposure, is associated with reduced cardiovascular disease mortality. However, hypoxia has also been reported to promote atherosclerosis by worsening lipid metabolism and inflammation. We sought to address these disparate reports by reducing the ambient oxygen exposure of ApoE-/- mice. We observed that long-term adaptation to 10% O2 (equivalent to oxygen content at ~5000 m), compared to 21% O2 (room air at sea level), resulted in a marked decrease in aortic atherosclerosis in ApoE-/- mice. This effect was associated with increased expression of the anti-inflammatory cytokine interleukin-10 (IL-10), known to be anti-atherogenic and regulated by hypoxia-inducible transcription factor-1alpha (HIF-1alpha). Supporting these observations, ApoE-/- mice that were deficient in IL-10 (IL10-/- ApoE-/- double knockout) failed to show reduced atherosclerosis in 10% oxygen. Our study reveals a specific mechanism that can help explain the decreased prevalence of ischemic heart disease in populations living at high altitudes and identifies ambient oxygen exposure as a potential factor that could be modulated to alter pathogenesis. Key messages: Chronic low ambient oxygen exposure decreases atherosclerosis in mice. Anti-inflammatory cytokine IL-10 levels are increased by low ambient O2. This is consistent with the established role of HIF-1alpha in IL10 transactivation. Absence of IL-10 results in the loss of the anti-atherosclerosis effect of low O2. This mechanism may contribute to decreased atherosclerosis at high altitudes. PMID- 26830630 TI - Aggressive cavernous sinus dural arteriovenous fistula: Angioarchitecture analysis and embolization by various approaches. AB - BACKGROUND: Most cavernous sinus dural arteriovenous fistulas (CSDAVFs) present with benign neuro-ophthalmic symptoms. CSDAVFs manifesting with aggressive neurologic symptoms are rare. The purpose of this study was to analyze the different angioarchitectures of aggressive CSDAVFs and to report our experiences of embolization. METHODS: Over the past 10 years, a total of 118 CSDAVFs were managed by embolization. From the databases containing such patient information, nine patients (7.6%) were found to have aggressive CSDAVFs presenting with neurologic deficits. There were seven women and two men, ranging in age from 51 years to 78 years (mean, 66 years). We retrospectively analyzed the angioarchitectures of aggressive CSDAVFs, further reviewing patient and angiographic as well clinical outcomes after embolization. RESULTS: The cause of clinically aggressive CSDAVFs was insufficient fistula drainage because of occlusion (n = 6) or stenosis (n = 1) of the inferior petrous sinus (IPS) or compartment of IPS-cavernous sinus (n = 2) with fistula flow reflux to the veins of brainstem (n = 7) leading to brainstem ischemia, while two fistula flow reflux to the cortical vein leading to cerebral infarction. Transvenous embolization via IPS to fistula was achieved in one case; six patients underwent transorbital access, while transarterial embolization was performed in two cases. Total fistula occlusion was achieved in eight CSDAVFs. All patients had total (n = 7) or partial (n = 2) resolution of their symptoms gradually within 6 months. One patient undergoing transarterial embolization had limb weakness because of inadvertent pial artery occlusion. Their overall mean clinical follow-up period was 17 months. CONCLUSION: Aggressive CSDAVFs are associated with occlusion/stenosis of the IPS or compartment of IPS-cavernous sinus with leptomeningeal reflux. In this limited case series, aggressive CSDAVFs most presented with brainstem ischemia, followed by nonhemorrhagic/hemorrhagic stroke in the cerebrum. Embolization through various access routes is a feasible method to manage these aggressive CSDAVFs, with an acceptable level of periprocedural risks. PMID- 26830631 TI - A CBPR Study to Test the Impact of a Church-Based Health Empowerment Program on Health Behaviors and Health Outcomes of Black Adult Churchgoers. AB - Black adults in the United States are disproportionately affected by health disparities, such as overweight and obesity. Research suggests that Black adults engage in fewer health-promoting behaviors (e.g., physical activity and healthy eating) than their non-Hispanic White counterparts. These health-promoting behaviors are known protective factors against overweight/obesity and related health concerns. This community-based participatory research study employed a waitlist control design and a university-church partnership approach to test the impact of a church-based health-empowerment program designed to increase health promoting behaviors (called health-smart behaviors) and improve health indicators (e.g., reduce weight) among overweight/obese Black adult churchgoers. Results indicate that the intervention group (n = 37) experienced a significant increase in levels of healthy eating and physical activity and a significant decrease in weight compared to the waitlist control group (n = 33). Results from this study have implications for the design of church-based, culturally sensitive health promotion interventions to increase health-smart behaviors and ultimately prevent and reduce obesity and related diseases in Black communities. PMID- 26830632 TI - Continuous recovery of valine in a model mixture of amino acids and salt from Corynebacterium bacteria fermentation using a simulated moving bed chromatography. AB - The economical efficiency of valine production in related industries is largely affected by the performance of a valine separation process, in which valine is to be separated from leucine, alanine, and ammonium sulfate. Such separation is currently handled by a batch-mode hybrid process based on ion-exchange and crystallization schemes. To make a substantial improvement in the economical efficiency of an industrial valine production, such a batch-mode process based on two different separation schemes needs to be converted into a continuous-mode separation process based on a single separation scheme. To address this issue, a simulated moving bed (SMB) technology was applied in this study to the development of a continuous-mode valine-separation chromatographic process with uniformity in adsorbent and liquid phases. It was first found that a Chromalite PCG600C resin could be eligible for the adsorbent of such process, particularly in an industrial scale. The intrinsic parameters of each component on the Chromalite-PCG600C adsorbent were determined and then utilized in selecting a proper set of configurations for SMB units, columns, and ports, under which the SMB operating parameters were optimized with a genetic algorithm. Finally, the optimized SMB based on the selected configurations was tested experimentally, which confirmed its effectiveness in continuous separation of valine from leucine, alanine, ammonium sulfate with high purity, high yield, high throughput, and high valine product concentration. It is thus expected that the developed SMB process in this study will be able to serve as one of the trustworthy ways of improving the economical efficiency of an industrial valine production process. PMID- 26830633 TI - A simple, comprehensive, and miniaturized solvent extraction method for determination of particulate-phase polycyclic aromatic compounds in air. AB - The method allowed simultaneous characterization of PAHs, nitro-PAHs and quinones in atmospheric particulate matter. This method employs a miniaturized micro extraction step that uses 500 MUL of an acetonitrile-dichloromethane mix and instrumental analysis by means of a high-resolution GC-MS. The method was validated using the SRM1649b NIST standard reference material as well as deuterated internal standards. The results are in good agreement with the certified values and show recoveries between 75% and 145%. Limit of detection (LOD) values for PAHs were found to be between 0.5 pg (benzo[a]pyrene) to 2.1 pg (dibenzo[a,h]anthracene), for nitro-PAHs ranged between 3.2 pg (1 nitrobenzo[e]pyrene) and 22.2 pg (3-nitrophenanthrene), and for quinones ranged between 11.5 pg (1,4-naphthoquinone) and 458 pg (9,10-phenanthraquinone). The validated method was applied to real PM10 samples collected on quartz fiber filters. Concentrations in the PM10 samples ranged from 0.06 to 15 ng m(-3) for PAHs, from0.99) for the isomers, with limits of detection ranging from 1.62 to 3.33ng/mL. The average recovery values that were obtained from analyzing the spiked samples were calculated to be in the range of 87.04-105.20%. Moreover, the trace MSPD method required less reagents and a shorter extraction time in comparison with the traditional pharmacopoeia method and other reported approaches. The developed method was successfully applied for the determination of three real honeysuckle samples that were collected from different cultivated areas. PMID- 26830638 TI - Chemometrics-assisted high performance liquid chromatography-diode array detection strategy to solve varying interfering patterns from different chromatographic columns and sample matrices for beverage analysis. AB - This work reports a chemometrics-assisted high performance liquid chromatography diode array detection (HPLC-DAD) strategy to solve varying interfering patterns from different chromatographic columns and sample matrices for the rapid simultaneous determination of six synthetic colorants in five kinds of beverages with little sample pretreatment. The investigation was performed using two types of LC columns under the same elution conditions. Although analytes using different columns have different co-elution patterns that appear more seriously in complex backgrounds, all colorants were properly resolved by alternating trilinear decomposition (ATLD) method and accurate chromatographic elution profiles, spectral profiles as well as relative concentrations were obtained. The results were confirmed by those obtained from traditional HPLC-UV method at a particular wavelength and the results of both methods were consistent with each other. All results demonstrated that the proposed chemometrics-assisted HPLC-DAD method is accurate, economical and universal, and can be promisingly applied to solve varying interfering patterns from different chromatographic columns and sample matrices for the analysis of complex food samples. PMID- 26830639 TI - Successful inter-hospital transfer for extracorporeal membrane oxygenation after an amniotic fluid embolism induced cardiac arrest. PMID- 26830640 TI - Local anesthetic systemic toxicity: Continuing Professional Development. AB - PURPOSE: Regional anesthesia is enjoying a renaissance due in part to the advent of ultrasound guidance and the development of new techniques such as tissue plane blocks and local infiltration analgesia. The purpose of this Continuing Professional Development module is to provide practitioners with an understanding of the current state of knowledge surrounding local anesthetic systemic toxicity (LAST) in order to help them prevent and manage this complication more effectively. PRINCIPAL FINDINGS: The causes of LAST are multifactorial, but recognized risks include patient factors, drug doses, pharmacokinetics, and choice of regional anesthetic technique. Local anesthetic systemic toxicity produces a biphasic course of clinical events that generally begin with central nervous system excitation followed by inhibition. At the same time, it causes cardiovascular compromise due to dysrhythmias, myocardial depression, and reduced systemic vascular resistance. Clinical presentation can be highly variable, however, and atypical presentations are not uncommon. Local anesthetic systemic toxicity is prevented by careful choice and dosing of drugs, aspiration before injection, dose fractionation, use of intravascular markers and ultrasound guidance. The management of LAST includes adequate oxygenation and ventilation, seizure termination, maintenance of circulation, and intravenous lipid emulsion therapy. CONCLUSIONS: Local anesthetic systemic toxicity is a potentially lethal condition with protean manifestations, and anesthesiologists must understand its risks, prevention, and safe management. PMID- 26830641 TI - A "VL tube" for endotracheal intubation using video laryngoscopy. PMID- 26830642 TI - Dexmedetomidine during total knee arthroplasty performed under spinal anesthesia decreases opioid use: a randomized-controlled trial. AB - BACKGROUND: It remains unclear whether the opioid-sparing effects of dexmedetomidine seen in patients undergoing general anesthesia are reproducible in patients undergoing spinal anesthesia. We hypothesized that the administration of intravenous dexmedetomidine for sedation during total knee arthroplasty under spinal anesthesia would decrease postoperative morphine consumption in the first 24 hr following surgery. METHODS: We conducted this prospective double-blind randomized-controlled trial in 40 patients (American Society of Anesthesiologists physical status I-III) undergoing total knee arthroplasty with a standardized spinal anesthetic. Patients were randomized to receive either a dexmedetomidine loading dose of 0.5 ug.kg(-1) over ten minutes, followed by an infusion of 0.5 ug.kg.hr(-1) for the duration of the surgery, or a normal saline loading dose and an infusion of an equivalent volume. The primary outcome was the consumption of morphine delivered via patient-controlled analgesia in the first 24 hr following surgery. RESULTS: The mean (SD) cumulative morphine at 24 hr in the dexmedetomidine group was 29.2 (11.2) mg compared with 61.2 (17.2) mg in the placebo group (mean difference, 32.0 mg; 95% confidence interval, 22.7 to 41.2; P < 0.001). In the dexmedetomidine group, there was a delay in the time to first analgesic request (P = 0.003) and a reduction in the mean morphine use at six and 12 hr following surgery (both P < 0.001). CONCLUSIONS: Dexmedetomidine was associated with a significant decrease in morphine use in the first 24 hr following total knee arthroplasty. Our study shows that an intraoperative infusion of dexmedetomidine for sedation in patients receiving spinal anesthesia can produce postoperative analgesic effects. This offers another potential adjunct in the multimodal pain management of these patients. This trial was registered at ClinicalTrials.gov (identifier NCT02026141). PMID- 26830643 TI - Impact of thoracic epidural catheter threading distance on analgesia during the first 24 hours following thoracotomy: a randomized controlled trial. AB - PURPOSE: The purpose of this prospective randomized controlled trial was to determine the impact of thoracic epidural catheter threading distance on analgesia quality after thoracotomy. METHODS: We randomly assigned 120 elective thoracotomy patients to a thoracic epidural catheter threading distance of 3, 5, or 7 cm (groups 3CM, 5CM, and 7CM, respectively). Epidural bupivacaine 0.1% with fentanyl 2 ug.mL(-1) was administered according to a standardized protocol. Epidural analgesia quality was assessed at 60 min and 24 hr postoperatively for four measures: incidence of non-functioning epidurals; numerical rating score (NRS) < 4 at rest, while coughing, and during wound palpation; cold perception at the wound site; and cumulative dose of analgesic medication used. Our primary hypothesis was that, compared to threading distances of 3 and 5 cm, a threading distance of 7 cm was not inferior at providing an NRS < 4 while coughing at 60 min postoperatively, with a non-inferiority margin of 25% (absolute value) being significant. RESULTS: The incidence of NRS < 4 while coughing at 60 min was 74% (29/39) in group 7CM compared with 68% (54/80) in the combined 3CM and 5CM groups (absolute difference 7%; 95% confidence interval -11 to 23; P = 0.29). At both 60 min and 24 hr, differences between groups were similar regarding the number of non-functioning epidurals, NRS < 4, and suppressed cold sensation. Analgesic doses were similar in the three groups. CONCLUSIONS: This study found that a thoracic epidural catheter threading distance of 7 cm in the epidural space was not inferior to distances of 3 cm and 5 cm with respect to pain scores at 60 min postoperatively. This study was not powered to examine differences that could have clinical significance that were less than our a priori 25% non-inferiority margin. PMID- 26830644 TI - Falling after epidural analgesia: lessons from obstetric anesthesia. PMID- 26830645 TI - The effect of sevoflurane versus desflurane on postoperative catheter-related bladder discomfort in patients undergoing transurethral excision of a bladder tumour: a randomized controlled trial. AB - PURPOSE: Catheter-related bladder discomfort (CRBD) due to an indwelling urinary catheter can cause postoperative distress, and the mechanism underlying CRBD is linked to the activation of muscarinic receptors. Inhalation of anesthetic agents, such as sevoflurane and desflurane, has differential inhibitory effects on muscarinic receptors. We aimed to compare the effect of intraoperative sevoflurane vs desflurane inhalation on postoperative CRBD. METHODS: Eighty-nine patients undergoing transurethral resection of a bladder tumour (TURBT) were randomly allocated to two groups. The sevoflurane group (n = 45) and the desflurane group (n = 44) received the respective inhalational agents for maintenance of general anesthesia. The incidence and severity (mild/moderate/severe) of CRBD were assessed at zero, one, six, and 24 hr postoperatively. RESULTS: Catheter-related bladder discomfort during the first 24 hr postoperatively occurred in 34/45 (76%) patients receiving sevoflurane compared with 41/44 (93%) patients receiving desflurane [absolute difference 18%; 95% confidence interval [CI], 2 to 33; P = 0.039]. The differences in the rate of CRBD between the sevoflurane and desflurane groups at zero, one, and six hours postoperatively were 24% (95% CI, 7 to 40; P = 0.012), 33% (95% CI, 15 to 49; P = 0.001), and 26% (95% CI, 6 to 43; P = 0.019), respectively. The incidence of moderate to severe CRBD and the number of patients treated with tramadol for CRBD were comparable between the two groups. CONCLUSIONS: As a maintenance agent of general anesthesia, sevoflurane reduced the incidence of early postoperative CRBD in patients undergoing TURBT when compared with desflurane. The protocol for this clinical trial was registered at ClinicalTrials.gov (NCT02096224). PMID- 26830646 TI - Lipomatous meningioma: a rare subtype of the meningioma. PMID- 26830647 TI - Case report: absence-status as late reexacerbation of genetic epilepsy of adolescence. PMID- 26830648 TI - Unexplicated hyperammonemic encephalopathy: remember the old urinary diversions! PMID- 26830649 TI - Injury of the Papez circuit in a patient with provoked confabulation following subarachnoid hemorrhage: a diffusion tensor tractography study. PMID- 26830650 TI - Transesophageal Echocardiographic Measurement of Cardiac Index by the Prosthetic Mitral Valve Method Is Not Similar to the Continuous Thermodilution Method Via a Pulmonary Artery Catheter. AB - OBJECTIVE: To compare the agreement of cardiac index measurements between transesophageal echocardiography across the prosthetic mitral valve and the continuous thermodilution method through a pulmonary artery catheter (PAC-TD) in patients undergoing double-valve replacement. DESIGN: Observational prospective study. SETTING: University hospital. PARTICIPANTS: Twenty-five patients undergoing double-valve replacement (12 men and 13 women, age 25-78 years, ASA III-IV, NYHA II-III, LVEF>=45%). Patients were grouped according to their prosthesis (mechanical prosthesis v bioprosthesis). INTERVENTIONS: All patients underwent cardiac index assessment during double-valve replacement. MEASUREMENTS AND MAIN RESULTS: Cardiac index across the prosthetic mitral valve was measured simultaneously using transesophageal echocardiography (CI(MV)) and PAC-TD (CI(PAC)) at 15, 30, 45, and 60 minutes after weaning from cardiopulmonary bypass, and at 0, 15, and 30 minutes after incision closure. A correlation was present between CI(MV) and CI(PAC) in both groups (mechanical prosthesis: r = 0.47, p<0.01; bioprosthesis: r = 0.60, p<0.01). In the mechanical prosthesis group, the bias between techniques (CI(PAC) v CI(MV)) was-0.5 L/min/m(2) (95% CI: 1.97 to 0.97), and error was 55%. In the bioprosthesis group, the bias between both techniques was-1.3 L/min/m(2) (95% CI:-3.1 to 0.5), and error was 56%. CONCLUSIONS: A relatively weak correlation and lack of agreement between values of CI(PAC) and CI(MV) were observed in patients undergoing double-valve replacement. Therefore, transesophageal echocardiography might not be interchangeable with PAC-TD for measuring cardiac output or cardiac index. A regression equation is needed to correct the probable value of CI(PAC). CI(MV) might be useful as a quantitative or semi-quantitative cardiac output measurement. PMID- 26830651 TI - Exceptional damage-tolerance of a medium-entropy alloy CrCoNi at cryogenic temperatures. AB - High-entropy alloys are an intriguing new class of metallic materials that derive their properties from being multi-element systems that can crystallize as a single phase, despite containing high concentrations of five or more elements with different crystal structures. Here we examine an equiatomic medium-entropy alloy containing only three elements, CrCoNi, as a single-phase face-centred cubic solid solution, which displays strength-toughness properties that exceed those of all high-entropy alloys and most multi-phase alloys. At room temperature, the alloy shows tensile strengths of almost 1 GPa, failure strains of ~70% and KJIc fracture-toughness values above 200 MPa m(1/2); at cryogenic temperatures strength, ductility and toughness of the CrCoNi alloy improve to strength levels above 1.3 GPa, failure strains up to 90% and KJIc values of 275 MPa m(1/2). Such properties appear to result from continuous steady strain hardening, which acts to suppress plastic instability, resulting from pronounced dislocation activity and deformation-induced nano-twinning. PMID- 26830654 TI - Are neighborhoods causal? Complications arising from the 'stickiness' of ZNA. AB - Are neighborhoods causal? The answer remains elusive. Armed with new multilevel methods, enthusiasm for neighborhoods research surged at the turn of the century. However, a wave of skepticism has arisen based on the difficulty of drawing causal inferences from observational studies in which selection to neighborhoods is non-random. Researchers have sought answers from experimental and quasi experimental studies of movers vs. stayers. We develop two related concepts in this essay in the hopes of shedding light on this problem. First, the inceptive environment into which persons are born (which we term ZNA for Zip code Nativity Area) exerts a potentially powerful causal impact on health. Detecting that causal effect is challenging for reasons similar that obtain in other fields (including genetics). Second, we explicate the problem of neighborhood 'stickiness' in terms of the persistence of neighborhood treatment assignment, and argue that under-appreciation of stickiness has led to systematic bias in causal estimates of neighborhoods proportional to the degree of stickiness. In sticky contexts, failure to account for the lasting influences of ZNA by adjusting for intermediate individual socioeconomic and health variables on the causal pathway can result in neighborhood effects estimates that are biased toward the null. We follow with an example drawn from evidence of neighborhood 'stickiness' and obesity. The stickiness of ZNA cautions us that experimental evidence may be insufficient or misleading as a solution to causal inference problems in neighborhood research. PMID- 26830652 TI - Under the hood of statistical learning: A statistical MMN reflects the magnitude of transitional probabilities in auditory sequences. AB - Within the framework of statistical learning, many behavioural studies investigated the processing of unpredicted events. However, surprisingly few neurophysiological studies are available on this topic, and no statistical learning experiment has investigated electroencephalographic (EEG) correlates of processing events with different transition probabilities. We carried out an EEG study with a novel variant of the established statistical learning paradigm. Timbres were presented in isochronous sequences of triplets. The first two sounds of all triplets were equiprobable, while the third sound occurred with either low (10%), intermediate (30%), or high (60%) probability. Thus, the occurrence probability of the third item of each triplet (given the first two items) was varied. Compared to high-probability triplet endings, endings with low and intermediate probability elicited an early anterior negativity that had an onset around 100 ms and was maximal at around 180 ms. This effect was larger for events with low than for events with intermediate probability. Our results reveal that, when predictions are based on statistical learning, events that do not match a prediction evoke an early anterior negativity, with the amplitude of this mismatch response being inversely related to the probability of such events. Thus, we report a statistical mismatch negativity (sMMN) that reflects statistical learning of transitional probability distributions that go beyond auditory sensory memory capabilities. PMID- 26830655 TI - Erratum: Griffiths phase behaviour in a frustrated antiferromagnetic intermetallic compound. PMID- 26830653 TI - Age-dependent inverse correlations in CSF and plasma amyloid-beta(1-42) concentrations prior to amyloid plaque deposition in the brain of 3xTg-AD mice. AB - Amyloid-beta (Abeta) plays a critical role as a biomarker in Alzheimer's disease (AD) diagnosis. In addition to its diagnostic potential in the brain, recent studies have suggested that changes of Abeta level in the plasma can possibly indicate AD onset. In this study, we found that plasma Abeta(1-42) concentration increases with age, while the concentration of Abeta(1-42) in the cerebrospinal fluid (CSF) decreases in APPswe, PS1M146V and TauP301L transgenic (3xTg-AD) mice, if measurements were made before formation of ThS-positive plaques in the brain. Our data suggests that there is an inverse correlations between the plasma and CSF Abeta(1-42) levels until plaques form in transgenic mice's brains and that the plasma Abeta concentration possesses the diagnostic potential as a biomarker for diagnosis of early AD stages. PMID- 26830656 TI - Graphene field-effect transistor array with integrated electrolytic gates scaled to 200 mm. AB - Ten years have passed since the beginning of graphene research. In this period we have witnessed breakthroughs both in fundamental and applied research. However, the development of graphene devices for mass production has not yet reached the same level of progress. The architecture of graphene field-effect transistors (FET) has not significantly changed, and the integration of devices at the wafer scale has generally not been sought. Currently, whenever an electrolyte-gated FET (EGFET) is used, an external, cumbersome, out-of-plane gate electrode is required. Here, an alternative architecture for graphene EGFET is presented. In this architecture, source, drain, and gate are in the same plane, eliminating the need for an external gate electrode and the use of an additional reservoir to confine the electrolyte inside the transistor active zone. This planar structure with an integrated gate allows for wafer-scale fabrication of high-performance graphene EGFETs, with carrier mobility up to 1800 cm(2) V(-1) s(-1). As a proof of principle, a chemical sensor was achieved. It is shown that the sensor can discriminate between saline solutions of different concentrations. The proposed architecture will facilitate the mass production of graphene sensors, materializing the potential of previous achievements in fundamental and applied graphene research. PMID- 26830659 TI - Corrigendum: Direct Observation of Long Electron-Hole Diffusion Distance in CH3NH3PbI3 Perovskite Thin Film. PMID- 26830657 TI - Glutamatergic axon-derived BDNF controls GABAergic synaptic differentiation in the cerebellum. AB - To study mechanisms that regulate the construction of inhibitory circuits, we examined the role of brain-derived neurotrophic factor (BDNF) in the assembly of GABAergic inhibitory synapses in the mouse cerebellar cortex. We show that within the cerebellum, BDNF-expressing cells are restricted to the internal granular layer (IGL), but that the BDNF protein is present within mossy fibers which originate from cells located outside of the cerebellum. In contrast to deletion of TrkB, the cognate receptor for BDNF, deletion of Bdnf from cerebellar cell bodies alone did not perturb the localization of pre- or postsynaptic constituents at the GABAergic synapses formed by Golgi cell axons on granule cell dendrites within the IGL. Instead, we found that BDNF derived from excitatory mossy fiber endings controls their differentiation. Our findings thus indicate that cerebellar BDNF is derived primarily from excitatory neurons--precerebellar nuclei/spinal cord neurons that give rise to mossy fibers--and promotes GABAergic synapse formation as a result of release from axons. Thus, within the cerebellum the preferential localization of BDNF to axons enhances the specificity through which BDNF promotes GABAergic synaptic differentiation. PMID- 26830660 TI - E-H (E = B, Si, Ge) bond activation of pinacolborane, silanes, and germanes by nucleophilic palladium carbene complexes. AB - The reactivity of two nucleophilic palladium carbenes, [PC(sp(2))P]Pd(PMe3) and [PC(sp(2))P]Pd(PPh3), where [PC(sp(2))P] = bis[2-(di-iso propylphosphino)phenyl]methylene, toward the E-H bond activation of Ph4-nEHn (E = Si, Ge; n = 1-3) and pinacolborane (HBpin) is discussed. Unlike previous reports, both types of isomer species, hydride [PC(EHn-1Ph4-n)P]PdH or [PC(Bpin)P]PdH and silyl/germyl [PC(H)P]Pd(EHn-1Ph4-n), were observed depending on the substrate and the phosphine ligand, showing that the polarity of the Pd-C bond can be tuned by the phosphine substituents. PMID- 26830658 TI - Additive enhancement of wound healing in diabetic mice by low level light and topical CoQ10. AB - Diabetes, a highly prevalent disease that affects 9.3% of Americans, often leads to severe complications and slow wound healing. Preclinical studies have suggested that low level light therapy (LLLT) can accelerate wound healing in diabetic subjects, but significant improvements must be made to overcome the absence of persuasive evidence for its clinical use. We demonstrate here that LLLT can be combined with topical Coenzyme Q10 (CoQ10) to heal wounds in diabetic mice significantly faster than LLLT alone, CoQ10 alone, or controls. LLLT followed by topical CoQ10 enhanced wound healing by 68~103% in diabetic mice in the first week and more than 24% in the second week compared with untreated controls. All wounds were fully healed in two weeks following the dual treatment, in contrast to only 50% wounds or a fewer being fully healed for single or sham treatment. The accelerated healing was corroborated by at least 50% higher hydroxyproline levels, and tripling cell proliferation rates in LLLT and CoQ10 treated wounds over controls. The beneficial effects on wound healing were probably attributed to additive enhancement of ATP production by LLLT and CoQ10 treatment. The combination of LLLT and topical CoQ10 is safe and convenient, and merits further clinical study. PMID- 26830661 TI - Short-term memory trace mediated by termination kinetics of olfactory receptor. AB - Odorants activate receptors in the peripheral olfactory neurons, which sends information to higher brain centers where behavioral valence is determined. Movement and airflow continuously change what odor plumes an animal encounters and little is known about the effect one plume has on the detection of another. Using the simple Drosophila melanogaster larval model to study this relationship we identify an unexpected phenomenon: response to an attractant can be selectively blocked by previous exposure to some odorants that activates the same receptor. At a mechanistic level, we find that exposure to this type of odorant causes prolonged tonic responses from a receptor (Or42b), which can block subsequent detection of a strong activator of that same receptor. We identify naturally occurring odorants with prolonged tonic responses for other odorant receptors (Ors) as well, suggesting that termination-kinetics is a factor for olfactory coding mechanisms. This mechanism has implications for odor-coding in any system and for designing applications to modify odor-driven behaviors. PMID- 26830662 TI - Low stress resilience in late adolescence and risk of hypertension in adulthood. AB - OBJECTIVE: Greater blood pressure reactivity to psychological stress has been associated with higher risk of developing hypertension. We hypothesised that low stress resilience based on psychological assessment early in life is associated with hypertension in adulthood. METHODS: National cohort study of 1,547,182 military conscripts in Sweden during 1969-1997 (97-98% of all 18-year-old males) without prior history of hypertension, who underwent standardised psychological assessment by trained psychologists for stress resilience (1-9 scale), and were followed up for hypertension identified from outpatient and inpatient diagnoses during 1969-2012 (maximum age 62). RESULTS: 93,028 men were diagnosed with hypertension in 39.4 million person-years of follow-up. Adjusting for body mass index (BMI), family history and socioeconomic factors, low stress resilience at age 18 was associated with increased risk of hypertension in adulthood (lowest vs highest quintile: HR 1.43; 95% CI 1.40 to 1.46; p < 0.001; incidence rates, 278.7 vs 180.0 per 100,000 person-years), including a strong linear trend across the full range of stress resilience (p(trend) < 0.0001). We also found a positive additive interaction between stress resilience and BMI (p < 0.001), indicating that low stress resilience accounted for more hypertension cases among those with high BMI. Men with a combination of low stress resilience and high BMI had a more than threefold risk of hypertension. CONCLUSIONS: These findings suggest that low stress resilience may contribute to etiological pathways for hypertension and accounts for more cases among those with high BMI. If confirmed, this knowledge may help inform better preventive interventions by addressing psychosocial risk factors and stress management across the lifespan. PMID- 26830663 TI - Cardiovascular effects and safety of long-term colchicine treatment: Cochrane review and meta-analysis. AB - Colchicine is an old anti-inflammatory drug that has shown substantial cardiovascular benefits in recent trials. We systematically reviewed cardiovascular benefits and harms of colchicine in any population and specifically in patients with high cardiovascular risk. We evaluated randomised controlled trials comparing colchicine over at least 6 months versus any control in any adult population. Primary outcomes were all-cause mortality, myocardial infarction and adverse events. Cardiovascular mortality was a secondary outcome. We included 39 trials with 4992 patients. The quality of evidence for mortality outcomes and myocardial infarction was moderate but lower for adverse events. Colchicine had no effect on all-cause mortality (RR 0.94, 95% CI 0.82 to 1.09; I(2)=27%; 30 trials). Cardiovascular mortality was reduced in some but not all meta-analytical models (random-effects RR 0.34, 0.09 to 1.21, I(2)=9%; Peto's OR 0.24, 0.09 to 0.64, I(2)=15%; Mantel-Haenszel fixed-effect RR 0.20, 0.06 to 0.68, I(2)=0%; 7 trials). The risk for myocardial infarction was reduced (RR 0.20, 0.07 to 0.57; 2 trials). There was no effect on total adverse events (RR 1.52, 0.93 to 2.46, I(2)=45%; 11 trials) but gastrointestinal intolerance was increased (RR 1.83, 1.03 to 3.26, I(2)=74%; 11 trials). Reporting of serious adverse events was inconsistent; no event occurred over 824 patient-years (4 trials). Effects in high cardiovascular risk populations were similar (4 trials; 1230 patients). We found no evidence supporting colchicine doses above 1 mg/day. Colchicine may have substantial cardiovascular benefits; however, there is sufficient uncertainty about its benefit and harm to indicate the need for large-scale trials to further evaluate this inexpensive, promising treatment in cardiovascular disease. PMID- 26830664 TI - Pulmonary artery growth after arterial duct stenting in completely duct-dependent pulmonary circulation. AB - OBJECTIVE: Significant and balanced pulmonary artery (PA) growth following arterial duct (AD) stenting has already been reported in literature. However, no data are so far available about the role of this percutaneous approach in promoting PA growth in the case of congenital heart disease (CHD) with completely duct-dependent pulmonary blood flow (CDD-PBF). Aim of this study was to evaluate the effect of AD stenting in this pathophysiological setting. METHODS: PA growth was evaluated as Nakata index and McGoon ratio as well as individual PA z-score changes in 49 patients submitted to neonatal AD stenting according to their pathophysiology (CDD-PBF (n=15) versus multiple PBF sources (n=34)). RESULTS: Control angiography was performed 7.2+/-6.4 months (range 1-8, median 6) after AD stenting. In the whole population, significant and balanced PA growth was recorded (Nakata index+122+/-117%; left pulmonary artery (LPA) z-score +84+/-52%; right pulmonary artery (RPA) z-score +92+/-53% versus preprocedure, p<0.0001 for all comparisons). Percentage increase of global and branch vessel size was not significantly different in patients with CDD-PBF compared with those with multiple PBF sources (Nakata index 89+/-90% vs 144+/-124%; LPA z-score 63+/-40% vs 89+/-58%; RPA z-score 74+/-35% vs 100+/-57%, p=NS for all comparisons) as was final absolute PA size (Nakata index 237+/-90 vs 289+/-80 mm(2)/m(2), p=NS). CONCLUSIONS: Percutaneous AD stenting was associated with significant and balanced PA growth in CHD with completely duct-dependent pulmonary circulation over a short-term follow-up. Thus, it may be considered as an alternative to surgical palliation in this subset of patients. PMID- 26830665 TI - Prognostic implication of relative regional strain ratio in cardiac amyloidosis. AB - OBJECTIVE: Cardiac amyloidosis (CA) is a rapidly progressive disease that portends poor prognosis. Our objective was to evaluate the prognostic impact of relative regional strain ratio (RRSR, a measure of the relative apical sparing of longitudinal strain (LS)) in CA. METHODS: This is a retrospective study evaluating 97 patients with CA from 2004 to 2013. Patients were included if they met criteria for CA based on endomyocardial biopsy or advanced imaging criteria coupled with either extracardiac biopsy or genetic analysis. Baseline clinical and imaging data were collected and compared between light-chain amyloidosis (AL) (n=59) and transthyretin amyloidosis (ATTR) (n=38) subtypes. RRSR was defined as the average apical LS divided by the sum of the average mid and basal LS values. A Cox proportional hazards model was used to assess the effects of clinical and echocardiographic characteristics, including RRSR, on the outcome of time to death or heart transplantation. RESULTS: Despite younger age, the AL subtype had a statistically significant association with the composite outcome as compared with ATTR (p=0.022). Log-transformed RRSR was independently associated with the composite outcome at 5 years (HR 2.45 (1.36 to 4.40), p=0.003). Patients with low ejection fraction and high RRSR had the worst prognosis. In multivariable analysis, RRSR remained predictive of the primary outcome (p=0.018). Addition of covariates related to systolic function (global LS and ejection fraction) to the model attenuated this effect. CONCLUSIONS: High RRSR is adversely prognostic in patients with cardiac amyloid. This novel tool is both diagnostic and prognostic and may have implications in management and suitability for treatment. PMID- 26830667 TI - Comparison of the protective effects of intratympanic dexamethasone and methylprednisolone against cisplatin-induced ototoxicity. AB - OBJECTIVE: This study aimed to compare the efficacies of intratympanic dexamethasone and methylprednisolone in preventing in cisplatin-induced ototoxicity in rats. METHODS: Experimental groups of rats (n = 8 each) received intratympanic isotonic saline, intraperitoneal cisplatin and intratympanic isotonic saline, intraperitoneal cisplatin and intratympanic dexamethasone, or intraperitoneal cisplatin and intratympanic methylprednisolone. Distortion product otoacoustic emission thresholds were compared on days 0 and 10 in all rats, and correlations between drug effects and changes in cochlear histology were evaluated. RESULTS: Distortion product otoacoustic emission thresholds were comparable in groups III and IV (p > 0.05). Significant protection against cisplatin-induced ototoxicity was seen in groups III and IV compared with group II (p < 0.05). Dexamethasone and, to a lesser extent, methylprednisolone protected against cellular apoptosis in cisplatin-induced ototoxicity. CONCLUSION: Dexamethasone (and possibly methylprednisolone) may be clinically useful as an intratympanic chemopreventive agent to treat cisplatin ototoxicity. Future clinical studies should investigate the use of dexamethasone for this purpose in adult patients. PMID- 26830666 TI - LIPUS promotes spinal fusion coupling proliferation of type H microvessels in bone. AB - Low-intensity pulsed ultrasound (LIPUS) has been found to accelerate spinal fusion. Type H microvessels are found in close relation with bone development. We analyzed the role of type H vessels in rat spinal fusion model intervened by LIPUS. It was found LIPUS could significantly accelerate bone fusion rate and enlarge bone callus. Osteoblasts were specifically located on the bone meshwork of the allograft, and were surrounded by type H microvessels. LIPUS could significantly increase the quantity of osteoblasts during spine fusion, which process was coupled with elevated angiogenesis of type H microvessels. Our results suggest that LIPUS may be a noninvasive adjuvant treatment modality in spinal fusion for clinical use. The treatment is recommended for usage for at least one month. PMID- 26830668 TI - PRISMA harms checklist: improving harms reporting in systematic reviews. AB - INTRODUCTION: For any health intervention, accurate knowledge of both benefits and harms is needed. Systematic reviews often compound poor reporting of harms in primary studies by failing to report harms or doing so inadequately. While the PRISMA statement (Preferred Reporting Items for Systematic reviews and Meta Analyses) helps systematic review authors ensure complete and transparent reporting, it is focused mainly on efficacy. Thus, a PRISMA harms checklist has been developed to improve harms reporting in systematic reviews, promoting a more balanced assessment of benefits and harms. METHODS: A development strategy, endorsed by the EQUATOR Network and existing reporting guidelines (including the PRISMA statement, PRISMA for abstracts, and PRISMA for protocols), was used. After the development of a draft checklist of items, a modified Delphi process was initiated. The Delphi consisted of three rounds of electronic feedback followed by an in-person meeting. RESULTS: The PRISMA harms checklist contains four essential reporting elements to be added to the original PRISMA statement to improve harms reporting in reviews. These are reported in the title ("Specifically mention 'harms' or other related terms, or the harm of interest in the review"), synthesis of results ("Specify how zero events were handled, if relevant"), study characteristics ("Define each harm addressed, how it was ascertained (eg, patient report, active search), and over what time period"), and synthesis of results ("Describe any assessment of possible causality"). Additional guidance regarding existing PRISMA items was developed to demonstrate relevance when synthesising information about harms. CONCLUSION: The PRISMA harms checklist identifies a minimal set of items to be reported when reviewing adverse events. This guideline extension is intended to improve harms reporting in systematic reviews, whether harms are a primary or secondary outcome. PMID- 26830669 TI - Explaining Anomalies in Enamine Catalysis: "Downstream Species" as a New Paradigm for Stereocontrol. AB - Enantioselective organocatalysis by diarylprolinol ethers is remarkably selective and efficient for a wide range of transformations involving a number of different activation modes, including HOMO activation via enamines. A simple steric model based on facial discrimination in the attack of an enamine on an electrophile has been invoked to rationalize high enantioselectivity. In a number of reactions, however, experimental observations have persistently left us with mechanistic puzzles that fail to fit neatly into this simple picture. Further studies involving both kinetic profiling of reaction networks and NMR spectroscopic characterization of the structures of intermediate species helped us to address these puzzles. This work led to the proposal of a new paradigm for stereocontrol in asymmetric aminocatalysis, demonstrating that the ultimate stereochemical outcome may not, in fact, be determined solely in the stereogenic bond-forming step between enamine and electrophile. The identification of stable species occurring downstream from the addition of an electrophile to an enamine, and the discovery of kinetic features that are diagnostic of the presence of such species, allows development of a new mechanistic framework that reveals a hierarchical selection. Both kinetic and thermodynamic processes associated with downstream intermediates can exert an influence on the ultimate enantioselectivity. Interestingly, the role of these species may be either to enhance or to erode selectivity established at the enamine-electrophile step. The reversibility of steps preceding and subsequent to the stereogenic bond-forming step is an important factor, as are reaction parameters that may stabilize or destabilize intermediates, including the nature of the electrophile counterion and the solvent. These concepts hold implications for the future design and optimization of asymmetric catalytic processes, because such design does not necessarily feature the same parameters at the second hierarchical level as it does at the first. Examples presented to highlight these issues include the conjugate addition of aldehydes to nitroalkenes and the alpha-chlorination and alpha-selenylation of aldehdyes using diarylprolinol ether catalysts commonly assumed to follow a steric model for enantioselectivity. While the new paradigm for stereocontrol involving downstream intermediates is developed here for enamine catalysis, the same concepts may hold for other organocatalytic modes of activation. PMID- 26830670 TI - Highly Oxidized RO2 Radicals and Consecutive Products from the Ozonolysis of Three Sesquiterpenes. AB - The formation of highly oxidized multifunctional organic compounds (HOMs) from the ozonolysis of three sesquiterpenes, alpha-cedrene, beta-caryophyllene, and alpha-humulene, was investigated for the first time. Sesquiterpenes contribute 2.4% to the global carbon emission of biogenic volatile organic compounds (BVOCs) and can be responsible for up to 70% of the regional BVOC emissions. HOMs were detected with chemical ionization-atmospheric pressure interface-time-of-flight mass spectrometry and nitrate and acetate ionization. Acetate ions were more sensitive toward highly oxidized RO2 radicals containing a single hydroperoxide moiety. Under the chosen reaction conditions, product formation was dominated by highly oxidized RO2 radicals which react with NO, NO2, HO2, and other RO2 radicals under atmospheric conditions. The ozonolysis of sesquiterpenes resulted in molar HOM yields of 0.6% for alpha-cedrene (acetate), 1.8% for beta caryophyllene (acetate), and 1.4% for alpha-humulene (nitrate) afflicted with an uncertainty factor of 2. Molar yields of highly oxidized RO2 radicals were identical with HOM yields measuring the corresponding closed-shell products. HOM formation from ozonolysis of alpha-cedrene was explained by an autoxidation mechanism initiated by ozone attack at the double bond similar to that found in the ozonolysis of cyclohexene and limonene. PMID- 26830671 TI - Increased adhesion of Plasmodium falciparum infected erythrocytes to ICAM-1 in children with acute intestinal injury. AB - BACKGROUND: Children with severe malaria are at increased risk of invasive bacterial disease particularly infection with enteric gram-negative organisms. These organisms are likely to originate from the gut, however, how and why they breach the intestinal interface in the context of malaria infection remains unclear. One explanation is that accumulation of infected red blood cells (iRBCs) in the intestinal microvasculature contributes to tissue damage and subsequent microbial translocation which can be addressed through investigation of the impact of cytoadhesion in patients with malaria and intestinal damage. METHODS: Using a static adhesion assay, cytoadhesion of iRBCs was quantified in 48 children with malaria to recombinant proteins constitutively expressed on endothelial cell surfaces. Cytoadhesive phenotypes between children with and without biochemical evidence of intestinal damage [defined as endotoxemia or elevated plasma intestinal fatty acid binding protein (I-FABP)] was compared. RESULTS: The majority of parasites demonstrated binding to the endothelial receptors CD36 and to a lesser extent to ICAM-1. Reduced adhesion to CD36 but not adhesion to ICAM-1 or rosetting was associated with malarial anaemia (p = 0.004). Increased adhesion of iRBCs to ICAM-1 in children who had evidence of elevated I FABP (p = 0.022), a marker of intestinal ischaemia was observed. There was no correlation between the presence of endotoxemia and increased adhesion to any of the recombinant proteins. CONCLUSION: Increased parasite adhesion to ICAM-1 in children with evidence of intestinal ischaemia lends further evidence to a link between the cytoadherence of iRBCs in gut microvasculature and intestinal damage. PMID- 26830672 TI - Geniposide Suppresses Hepatic Glucose Production via AMPK in HepG2 Cells. AB - Geniposide is one of the main compounds in Gardenia jasminoides ELLIS and has many pharmacological activities, but its anti-hyperglycemic activity has not yet been fully explored. This study was designed to determine, for the first time, how geniposide from G. jasminoides regulates hepatic glucose production, and the underlying mechanisms. During in vitro study, we found the inhibitory effect of geniposide on the hepatic glucose production is partly through AMP-activated protein kinase (AMPK) activation in HepG2 cells. Geniposide significantly inhibited hepatic glucose production in a dose-dependent manner. AMPK, acetyl coenzyme A synthetase (ACC) and forkhead box class O1 (FoxO1) phosphorylation were stimulated by different concentrations of geniposide. In addition, the enzyme activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6 phosphatase (G6Pase) were all significantly suppressed. What is important is that these effects were partly reversed by (1) inhibition of AMPK activity by compound C, a selective AMPK inhibitor, and by (2) suppression of AMPKalpha expression by small interfering RNA (siRNA). In summary, geniposide potentially ameliorates hyperglycemia through inhibition of hepatic gluconeogenesis by modulation of the AMPK-FoxO1 signaling pathway. Geniposide or geniposide-containing medicinal plants could represent a promising therapeutic agent to prevent type 2 diabetes on gluconeogenesis. PMID- 26830673 TI - Hepatitis B and C prevalence among hemodialysis patients in the West Bank hospitals, Palestine. AB - BACKGROUND: Hepatitis B and C virus infection is a lead cause of morbidity and mortality among hemodialysis patients. Yet, little research has focused on the morbidity measures of these serious disorders in low and middle income countries. The study aims to estimate the prevalence of hepatitis B and C among hemodialysis patients in the West Bank hospitals in Palestine. METHODS: A retrospective medical records review design was performed for all governmental and private hospitals in the West Bank which provide hemodialysis services for the patients. Data was retrieved from the patients' medical files and from the computerized health information system in some hemodialysis centers. SPSS software version 16 was used for data entry and analysis. RESULTS: In overall, 868 hemodialysis patients attending nine hemodialysis hospitals in the West Bank was recruited. The overall prevalence of hepatitis B virus was found to be 3.8% (33 cases) with a range from 0.0% (in Jericho and Qalqelia districts) to 11.8% (in Bethlehem district). Regarding hepatitis C virus, the overall prevalence was estimated around 7.4% (64 cases) with a range from 2.9% (in Nablus district) to 15.9% (in Qalqelia district). CONCLUSIONS: Although relatively low prevalence of both hepatitis B and C virus was found in a couple of hemodialysis hospitals, some higher prevalence values urge for the implementation of stricter infection prevention measures and more effective follow up procedures. PMID- 26830675 TI - Case-based learning and multiple choice questioning methods favored by students. AB - BACKGROUND: Investigating and understanding how students learn on their own is essential to effective teaching, but studies are rarely conducted in this context. A major aim within medical education is to foster procedural knowledge. It is known that case-based questioning exercises drive the learning process, but the way students deal with these exercises is explored little. METHODS: This study examined how medical students deal with case-based questioning by evaluating 426 case-related questions created by 79 fourth-year medical students. The subjects covered by the questions, the level of the questions (equivalent to United States Medical Licensing Examination Steps 1 and 2), and the proportion of positively and negatively formulated questions were examined, as well as the number of right and wrong answer choices, in correlation to the formulation of the question. RESULTS: The evaluated case-based questions' level matched the United States Medical Licensing Examination Step 1 level. The students were more confident with items aiming on diagnosis, did not reject negatively formulated questions and tended to prefer handling with right content, while keeping wrong content to a minimum. CONCLUSION: These results should be taken into consideration for the formulation of case-based questioning exercises in the future and encourage the development of bedside teaching in order to foster the acquisition of associative and procedural knowledge, especially clinical reasoning and therapy-oriented thinking. PMID- 26830674 TI - Co-overexpression of TGF-beta and SOX9 via rAAV gene transfer modulates the metabolic and chondrogenic activities of human bone marrow-derived mesenchymal stem cells. AB - BACKGROUND: Articular cartilage has a limited potential for self-healing. Transplantation of genetically modified progenitor cells like bone marrow-derived mesenchymal stem cells (MSCs) is an attractive strategy to improve the intrinsic repair capacities of damaged articular cartilage. METHODS: In this study, we examined the potential benefits of co-overexpressing the pleiotropic transformation growth factor beta (TGF-beta) with the cartilage-specific transcription factor SOX9 via gene transfer with recombinant adeno-associated virus (rAAV) vectors upon the biological activities of human MSCs (hMSCs). Freshly isolated hMSCs were transduced over time with separate rAAV vectors carrying either TGF-beta or sox9 in chondrogenically-induced aggregate cultures to evaluate the efficacy and duration of transgene expression and to monitor the effects of rAAV-mediated genetic modification upon the cellular activities (proliferation, matrix synthesis) and chondrogenic differentiation potency compared with control conditions (lacZ treatment, sequential transductions). RESULTS: Significant, prolonged TGF-beta/sox9 co-overexpression was achieved in chondrogenically-induced hMSCs upon co-transduction via rAAV for up to 21 days, leading to enhanced proliferative, biosynthetic, and chondrogenic activities relative to control treatments, especially when co-applying the candidate vectors at the highest vector doses tested. Optimal co-administration of TGF-beta with sox9 also advantageously reduced hypertrophic differentiation of the cells in the conditions applied here. CONCLUSION: The present findings demonstrate the possibility of modifying MSCs by combined therapeutic gene transfer as potent future strategies for implantation in clinically relevant animal models of cartilage defects in vivo. PMID- 26830676 TI - Protocol: simulation training to improve 9-1-1 dispatcher identification of cardiac arrest. AB - BACKGROUND: 9-1-1 dispatchers are often the first contact for bystanders witnessing an out-of-hospital cardiac arrest. In the time before Emergency Medical Services arrives, dispatcher identification of the need for, and provision of Telephone-CPR (T-CPR) can improve survival. Our study aims to evaluate the use of phone-based standardized patient simulation training to improve identification of the need for T-CPR and shorten time to start of T-CPR instructions. METHODS/DESIGN: The STAT-911 study is a randomized controlled trial. We will recruit 160 dispatchers from 9-1-1 call-centers in the Pacific Northwest; they are randomized to an intervention or control group. Intervention participants complete four telephone simulation training sessions over 6-8 months. Training sessions consist of three mock 9-1-1 calls, with a standardized patient playing a caller witnessing a medical emergency. After the mock calls, an instructor who has been listening in and scoring the dispatcher's call management, connects to the dispatcher and provides feedback on select call processing skills. After the last training session, all participants complete the simulation test: a call session that includes two mock 9-1-1 calls of medium complexity. During the study, audio from all actual cardiac arrest calls handled by the dispatchers will be collected. All dispatchers complete a baseline survey, and after the intervention, a follow-up survey to measure confidence. Primary outcomes are proportion of calls where dispatchers identify the need for T-CPR, and time to start of T-CPR, assessed by comparing performance on two calls in the simulation test. Secondary outcomes are proportion of actual cardiac arrest calls in which dispatchers identify the need for T-CPR and time to start of T-CPR; performance on call-taking skills during the simulation test; self-reported confidence in the baseline and follow-up surveys; and calculated costs of the intervention training sessions and projected costs for field implementation of training sessions. DISCUSSION: The STAT-911 study will evaluate if over-the-phone simulation training with standardized patients can improve 9-1-1 dispatchers' ability identify the need for, and promptly begin T-CPR. Furthermore, it will advance knowledge on the effectiveness of simulation training for health services phone-operators interacting with clients, patients, or bystanders in diagnosis, triage, and treatment decisions. TRIAL REGISTRATION: ClinicalTrials.gov REGISTRATION NUMBER: NCT01972087 . Registered 23 October 2013. PMID- 26830679 TI - Strengthening partnerships between Black Churches and HIV service providers in the United States. AB - Across the United States, Black Churches play a significant role among the Black community and are increasingly being used to deliver Human Immunodeficiency Virus (HIV) prevention services. This study sought to investigate HIV service providers' strategies for strengthening partnerships with churches to deliver HIV prevention services. Using a community-based participatory research approach, an HIV coalition and an academic institution formed a partnership to address the study aim. Individual interviews (n = 16) were conducted with providers from medical institutions and HIV social support agencies. A thematic analysis focusing on recommendations for addressing the challenges and benefits of partnership with churches for HIV services was conducted. Participants' interest in and intention to work with churches, as well as their comfort level discussing sexual health-related topics with religious congregations, was high. Four themes emerged to highlight the different perspectives of service providers' recommendations for addressing challenges and strengthening partnerships with churches to deliver HIV services including: (1) carefully selecting churches and HIV services to provide, (2) gaining "buy-in" and support of church leadership, (3) taking advantage of conflict with church doctrine, and (4) choosing appropriate delivery strategies. Study findings demonstrate that although challenges exist, heath service providers in this region of the United States may be interested in addressing HIV among faith communities. Study findings also provide concrete solutions to previously documented barriers to HIV prevention in Black Churches. Such information will benefit researchers and practitioners seeking to expand effective HIV prevention efforts with Black Churches in communities who bear a disproportionate burden of HIV infections. PMID- 26830678 TI - No differences in clinical outcomes with the addition of viral load testing to CD4 cell count monitoring among HIV infected participants receiving ART in rural Uganda: Long-term results from the Home Based AIDS Care Project. AB - BACKGROUND: We compared clinical outcomes among HIV-infected participants receiving ART who were randomized to viral load (VL) and CD4 cell count monitoring in comparison to CD4 cell count monitoring alone in Tororo, Uganda. METHODS: Beginning in May 2003, participants with CD4 cell counts <250 cells/MUL or WHO stage 3 or 4 disease were randomized to clinical monitoring alone, clinical monitoring plus quarterly CD4 cell counts (CD4-only); or clinical monitoring, quarterly CD4 cell counts and quarterly VL testing (CD4-VL). In 2007, individuals in clinical monitoring arm were re-randomized to the other two arms and all participants were followed until March 31, 2009. We used Cox Proportional Hazard models to determine if study arm was independently associated with the development of opportunistic infections (OIs) or death. RESULTS: We randomized 1211 participants to the three original study arms and 331 surviving participants in the clinical monitoring arm were re-randomized to the CD4-VL and CD4 only arms. At enrolment the median age was 38 years and the median CD4 cell count was 134 cells/MUL. Over a median of 5.2 years of follow-up, 37 deaths and 35 new OIs occurred in the VL-CD4 arm patients, 39 deaths and 42 new OIs occurred in CD4 only patients. We did not observe an association between monitoring arm and new OIs or death (AHR =1.19 for CD4-only vs. CD4-VL; 95 % CI 0.82-1.73). CONCLUSION: We found no differences in clinical outcomes associated with the addition of quarterly VL monitoring to quarterly CD4 cell count monitoring. PMID- 26830677 TI - Targeting autophagy to sensitive glioma to temozolomide treatment. AB - Temozolomide (TMZ), an alkylating agent, is widely used for treating primary and recurrent high-grade gliomas. However, the efficacy of TMZ is often limited by the development of resistance. Recently, studies have found that TMZ treatment could induce autophagy, which contributes to therapy resistance in glioma. To enhance the benefit of TMZ in the treatment of glioblastomas, effective combination strategies are needed to sensitize glioblastoma cells to TMZ. In this regard, as autophagy could promote cell survival or autophagic cell death, modulating autophagy using a pharmacological inhibitor, such as chloroquine, or an inducer, such as rapamycin, has received considerably more attention. To understand the effectiveness of regulating autophagy in glioblastoma treatment, this review summarizes reports on glioblastoma treatments with TMZ and autophagic modulators from in vitro and in vivo studies, as well as clinical trials. Additionally, we discuss the possibility of using autophagy regulatory compounds that can sensitive TMZ treatment as a chemotherapy for glioma treatment. PMID- 26830681 TI - Effect of centrifugation time on growth factor and MMP release of an experimental platelet-rich fibrin-type product. AB - Platelet-rich fibrin (PRF) has a controlled release of growth factors due to the fibrin matrix structure. Different centrifugation protocols were suggested for PRF preparation. Since the derivation method of PRF can alter its contents, in the present study it is aimed to investigate the cell contents and transforming growth factor beta-1 (TGF-beta1), platelet-derived growth factor (PDGF-AB), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-1 and-8 release from experimental PRF-type membranes obtained with different centrifugation times at 400 gravity. Three blood samples were collected from 20 healthy non-smoker volunteers. One tube was used for whole blood analyses. The other two tubes were centrifuged at 400 g for 10 minutes (group A) or 12 minutes (group B). Each experimental PRF-type membrane was placed in Dulbecco's Modified Eagle's Medium (DMEM)and at 1, 24 and 72 hours, TGF-beta1, PDGF-AB, VEGF, MMP-1 and -8 release amounts were analysed by enzyme-linked immunosorbent assay (ELISA). The blood cell count of membranes was determined by subtracting plasma supernatant and red blood cell (RBC) mixture from the whole blood cell counts. At 72 hours, the VEGF level of group B was statistically higher than that of group A (p = 0.040). The centrifugation time was not found to influence the release of other growth factors, enzymes and cell counts. Within the limits of the present study, it might be suggested that centrifugation time at a constant gravity has a significant effect on the VEGF levels released from experimental PRF-type membrane. It can be concluded that due to the importance of VEGF in the tissue healing process, membranes obtained at 12-minute centrifugation time may show a superior potential in wound healing. PMID- 26830680 TI - Structure, phylogeny, allelic haplotypes and expression of sucrose transporter gene families in Saccharum. AB - BACKGROUND: Sugarcane is an economically important crop contributing to about 80% of the world sugar production. Increasing efforts in molecular biological studies have been performed for improving the sugar yield and other relevant important agronomic traits. However, due to sugarcane's complicated genomes, it is still challenging to study the genetic basis of traits, such as sucrose accumulation. Sucrose transporters (SUTs) are critical for both phloem loading in source tissue and sucrose uptaking in sink tissue, and are considered to be the control points for regulating sucrose storage. However, no genomic study for sugarcane sucrose transporter (SsSUT) families has been reported up to date. RESULTS: By using comparative genomics and bacterial artificial chromosomes (BACs), six SUT genes were identified and characterized in S. spontaenum. Phylogenetic analyses revealed that the two pairs SsSUTs (SsSUT1/SsSUT3 and SsSUT5/SsSUT6) could be clustered together into two separate monocot specific SUT groups, while SsSUT2 and SsSUT4 were separated into the other two groups, with members from both dicot and monocot species. Gene structure comparison demonstrated that the number and position of exons/introns in SUTs were highly conserved among the close orthologs; in contrast, there were variations among the paralogous SUTs in Sacchuarm. Though with the high polyploidy level, gene allelic haplotype comparative analysis showed that the examined four SsSUT members exhibited conservations of gene structures and amino acid sequences among the allelic haplotypes accompanied by variations of intron sizes. Gene expression analyses were performed for tissues from seedlings under drought stress and mature plants of three Saccharum species (S.officinarnum, S.spotaneum and S.robustum). Both SUT1 and SUT4 expressed abundantly at different conditions. SUT2 had similar expression level in all of the examined tissues, but SUT3 was undetectable. Both of SUT5 and SUT6 had lower expression level than other gene member, and expressed stronger in source leaves and are likely to play roles in phloem loading. In the seeding plant leave under water stress, four genes SUT1, SUT2, SUT4 and SUT5 were detectable. In these detectable genes, SUT1 and SUT4 were down regulated, while, SUT2 and SUT5 were up regulated. CONCLUSIONS: In this study, we presented the first comprehensive genomic study for a whole gene family, the SUT family, in Saccharum. We speculated that there were six SUT members in the S. spotaneum genome. Out of the six members, SsSUTs, SsSUT5 and SsSUT6 were recent duplication genes accompanied by rapid evolution, while, SsSUT2 and SsSUT4 were the ancient members in the families. Despite the high polypoidy genome, functional redundancy may not exist among the SUTs allelic haplotypes supported by the evidence of strong purifying selection of the gene allele. SUT3 could be a low active member in the family because it is undetectable in our study, but it might not be a pseudogene because it harbored integrated gene structure. SUT1 and SUT4 were the main members for the sucrose transporter, while, these SUTs had sub-functional divergence in response to sucrose accumulation and plant development in Saccharum. PMID- 26830682 TI - Efficacy of proline in the treatment of menopause. AB - The amino acids in the placenta have multiple functions; however, the therapeutic effects of proline remain poorly for relief postmenopausal symptoms. The aim of present study was to evaluate the effects of proline in the treatment of menopause using in vitro and in vivo models. We assessed the therapeutic effects and regulatory mechanisms of proline by using MCF-7 estrogen-dependent cells, MG63 osteoblast cells, and ovariectomized mice model. An in vivo study was carried out in eight-week-old sham and ovariectomized group. The ovariectomized mouse was further subdivided into two groups administered orally with 17beta estradiol or proline (10 mg/kg/day) for eight weeks. Proline significantly increased cell proliferation and Ki-67 levels in MCF-7 cells and enhanced cell proliferation, alkaline phosphatase activity, extracellular signal-regulated kinase phosphorylation, and glutamyl-prolyl-tRNA synthetase activation in MG63 cells. The estrogen receptor-beta and estrogen-response elements luciferase activity were significantly increased by proline in MCF-7 and MG63 cells. In ovariectomized mice, oral administration of proline (10 mg/kg/day) for eight weeks significantly reduced body and vaginal weights. Proline also significantly increased serum estradiol and alkaline phosphatase levels, whereas serum luteinizing hormone was decreased by proline. In addition, detailed microcomputed tomography analysis showed that the proline notably enhanced bone mineral density, trabecular bone volume, and trabecular number in ovariectomized mice. Those findings implied that proline can be a promising candidate for the treatment of menopause. PMID- 26830683 TI - Magnetically Responsive Bone Marrow Mesenchymal Stem Cell-Derived Smooth Muscle Cells Maintain Their Benefits to Augmenting Elastic Matrix Neoassembly. AB - Abdominal aortic aneurysms (AAA) represent abnormal aortal expansions that result from chronic proteolytic breakdown of elastin and collagen fibers by matrix metalloproteases. Poor elastogenesis by adult vascular smooth muscle cells (SMCs) limits regenerative repair of elastic fibers, critical for AAA growth arrest. Toward overcoming these limitations, we recently demonstrated significant elastogenesis by bone marrow mesenchymal stem cell-derived SMCs (BM-SMCs) and their proelastogenesis and antiproteolytic effects on rat aneurysmal SMCs (EaRASMCs). We currently investigate the effects of super paramagnetic iron oxide nanoparticle (SPION) labeling of BM-SMCs, necessary to magnetically guide them to the AAA wall, on their functional benefits. Our results indicate that SPION labeling is noncytotoxic and does not adversely impact the phenotype and elastogenesis by BM-SMCs. In addition, SPION-BM-SMCs showed no changes in the ability of the BM-SMCs to stimulate elastin regeneration and attenuate proteolytic activity by EaRASMCs. Together, our results are promising toward the utility of SPIONs for magnetic targeting of BM-SMCs for in situ AAA regenerative repair. PMID- 26830684 TI - CD24 associates with EGFR and supports EGF/EGFR signaling via RhoA in gastric cancer cells. AB - BACKGROUND: CD24, a mucin-like membrane glycoprotein, plays a critical role in carcinogenesis, but its role in human gastric cancer and the underlying mechanism remains undefined. METHODS: The contents of CD24 and epidermal growth factor receptor (EGFR) in gastric cancer cells (SGC-7901 and BGC-823) and non-malignant gastric epithelial cells (GES-1) were evaluated by Western blotting assay. Cellular EGFR staining was examined by immunofluorescence assay. Cell migration rate was measured by wound healing assay. The effects of depletion/overexperssion of CD24 on EGFR expression and activation of EGF/EGFR singaling pathways were evaluated by immunofluorescence, qPCR, Western blotting and flow cytometry techniques. RhoA activity was assessed by pulldown assay. CD24 and EGFR expression patterns in human gastric tumor samples were also investigated by immunohistochemistry staining. RESULTS: CD24 was overexpressed in human gastric cancer cells. Ectopic expression of CD24 in gastric epithelial cells augmented the expression of EGFR, while knockdown of CD24 in gastric cancer cells decreased the level of EGFR and cell migration velocity. To further explore the mechanisms, we investigated the effect of CD24 expression on EGF/EGFR signaling. We noticed that this effect of CD24 on EGFR expression was dependent on promoting EGFR internalization and degradation. Lower ERK and Akt phosphorylations in response to EGF stimulation were observed in CD24-depleted cells. In addition, we noticed that the effect of CD24 on EGFR stability was mediated by RhoA activity in SGC 7901 gastric cancer cells. Analysis of gastric cancer specimens revealed a positive correlation between CD24 and EGFR levels and an association between CD24 expression and worse prognosis. CONCLUSION: Thus, these findings suggest for the first time that CD24 regulates EGFR signaling by inhibiting EGFR internalization and degradation in a RhoA-dependent manner in gastric cancer cells. PMID- 26830686 TI - Inhalative steroids as an individual treatment in symptomatic lung cancer patients with radiation pneumonitis grade II after radiotherapy - a single-centre experience. AB - PURPOSE: To assess efficacy of our single-centre experience with inhalative steroids (IS) in lung cancer patients with symptomatic radiation pneumonitis (RP) grade II. MATERIAL AND METHODS: Between 05/09 and 07/10, 24 patients (female, n = 8; male, n = 16) with lung cancer (non-small cell lung carcinoma [NSCLC]: n = 19; small cell lung cancer [SCLC]: n = 3; unknown histology: n = 2) and good performance status (ECOG <=1) received definitive radiotherapy to the primary tumour site and involved lymph nodes with concurrent chemotherapy (n = 18), sequential chemotherapy (n = 2) or radiation only (n = 4) and developed symptomatic RP grade II during follow-up. No patient presented with oxygen requiring RP grade III. The mean age at diagnosis was 66 years (range: 50-82 years). Nine patients suffered from chronic obstructive pulmonary disease (COPD) before treatment, and 18 patients had a smoking history (median pack years: 48). The mean lung dose was 15.5 Gy (range: 3.0-23.1 Gy). All patients were treated with IS. If a patient's clinical symptoms did not significantly improve within two weeks of IS therapy initiation, their treatment was switched to oral prednisolone. RESULTS: All 24 patients were initially treated with a high dose IS (budesonide 800 MUg 1-0-1) for 14 days. Of the patients, 18 showed a significant improvement of clinical symptoms and 6 patients did not show significant improvement of clinical symptoms and were classified as non-responders to IS. Their treatment was switched to oral steroids after two weeks (starting with oral prednisolone, 0.5 mg/kg bodyweight; at least 50 mg per day). All of these patients responded to the prednisolone. None of non-responders presented with increased symptoms of RP and required oxygen and / or hospitalization (RP grade III). The median follow-up after IS treatment initiation was 18 months (range: 4 66 months). The median duration of IS treatment and prednisolone treatment was 8.2 months (range: 3.0-48.3 months) and 11.4 months (range: 5.0-44.0 months), respectively. Of the 18 IS treatment responders, 2 (11.1 %) patients with pre existing grade 2 COPD still required IS (400 MUg twice a day) 45.0 and 48.3 months after radiotherapy, respectively. For the remaining 16 responders (88.9 %), IS therapy was stopped after 7.7 months (range: 3.0-18.2 months). None of the patients treated with IS developed any specific IS-related side effects such as oral candidiasis. CONCLUSION: This single-centre experience shows that high-dose IS is an individual treatment option for radiation-induced pneumonitis grade II in patients with a good performance status. PMID- 26830685 TI - Updated long-term survival for patients with metastatic colorectal cancer treated with liver resection followed by hepatic arterial infusion and systemic chemotherapy. AB - BACKGROUND AND OBJECTIVES: Patients who undergo liver resection for metastatic colorectal cancer (mCRC) have reported 5-year survivals ranging from 25% to 50%. The current study updated long-term survival for patients with resected liver metastases treated with adjuvant hepatic arterial infusion (HAI) and systemic (SYS) chemotherapy. METHODS: Updated survival and recurrence free survival for patients treated on four consecutive adjuvant protocols with HAI and SYS from 1991 to 2009. Patients were divided into two groups: those treated on protocols before 2003 and after 2003. Median follow-up for all patients was 11 years. RESULTS: All 287 patients enrolled in four prospective protocols after liver resection are included. Patients treated before 2003 had a median follow-up of 15 years, 5 and 10-year survivals of 56% [95%CI: 49-64%] and 40% [95%CI: 32-47%], respectively, and median survival of 71 months. Patients treated after 2003 had a median follow-up of 9 years, 5 and 10-year survivals of 78% [95%CI: 70-84%] and 61% [95%CI: 51-70%], respectively, and median survival has not been reached. CONCLUSIONS: Survival is improving for patients with mCRC who undergo liver resection. These data support the durability of long-term survival in patients who undergo resection followed by adjuvant HAI and SYS therapy. J. Surg. Oncol. 2016;113:477-484. (c) 2016 Wiley Periodicals, Inc. PMID- 26830687 TI - Increased pain relief with remifentanil does not improve the success rate of external cephalic version: a randomized controlled trial. AB - INTRODUCTION: Our objective was to compare the effect of two pain relief methods (remifentanil vs. nitrous oxide) on the success rate of external cephalic version. MATERIAL AND METHODS: We conducted a randomized open label parallel group controlled single-center clinical trial with sequential design, at Cruces University Hospital, Spain. Singleton pregnancies in noncephalic presentation at term that were referred for external cephalic version were assigned according to a balanced (1:1) restricted randomization scheme to analgesic treatment with remifentanil or nitrous oxide during the procedure. The primary endpoint was external cephalic version success rate. Secondary endpoints were adverse event rate, degree of pain, cesarean rate and perinatal outcomes. RESULTS: The trial was stopped early after the second interim analysis due to a very low likelihood of finding substantial differences in efficacy (futility). The external cephalic version success rate was the same in the two arms (31/60, 51.7%) with 120 women recruited, 60 in each arm. The mean pain score was significantly lower in the remifentanil group (3.2 +/- 2.4 vs. 6.0 +/- 2.3; p < 0.01). No differences were found in external cephalic version-related complications. There was a trend toward a higher frequency of adverse effects in the remifentanil group (18.3% vs. 6.7%, p = 0.10), with a significantly higher incidence rate (21.7 events/100 women vs. 6.7 events/100 women with nitrous oxide, p = 0.03). All reported adverse events were mild and reversible. CONCLUSIONS: Remifentanil for analgesia decreased external cephalic version-related pain but did not increase the success rate of external cephalic version at term and appeared to be associated with an increased frequency of mild adverse effects. PMID- 26830688 TI - Transient spurious intrathecal immunoglobulin synthesis in neurological patients after therapeutic apheresis. AB - BACKGROUND: The analysis of cerebrospinal fluid (CSF) is usually done under steady-state conditions, when proteins (e.g., immunoglobulins) reach diffusion equilibrium between blood and CSF. However, little data has been published on CSF analysis under non-steady-state conditions after therapeutic apheresis. By reducing serum proteins (e.g., immunoglobulins), while leaving CSF unchanged, therapeutic apheresis might cause spuriously altered intrathecal immunoglobulin fractions. METHODS: Based on the incidental finding of plasma exchange-induced increased intrathecal immunoglobulin fractions in a cohort of 12 unsystematically selected patients with various neurological disorders, we retrospectively investigated CSF results that had been raised during routine diagnostic work-up from 41 consecutive neurological patients (predominantly Guillain-Barre syndrome and autoimmune encephalitis) treated with plasmapheresis or immunoadsorption in a tertiary care university hospital in whom lumbar puncture (LP) was performed after a varying number of treatments of therapeutic apheresis. RESULTS: Only when LP was performed 1 day after therapeutic apheresis, spurious quantitative intrathecal immunoglobulin (Ig) synthesis of at least one subclass (IgG, IgA and/or IgM) was found in 68.4 % of the patients, irrespective of the number of treatments, in all age groups and independent of other previous immunotherapies (e.g., steroids). This phenomenon occurred only transiently and was almost always accompanied by an elevation of the IgG index. In one patient, an elevated IgG index was noticed even 2 days after plasmapheresis. Neither quantitative Ig synthesis, nor elevated IgG index was observed when the LP was performed three or more days after therapeutic apheresis. CONCLUSIONS: Spurious quantitative intrathecal Ig synthesis and increased IgG index are common findings shortly after plasmapheresis or immunoadsorption due to altered serum immunoglobulin levels. Knowledge of this phenomenon is needed for clinicians to prevent false interpretations leading to unnecessary diagnostic and therapeutic procedures. Misdiagnoses can be avoided by considering the characteristic CSF constellation including absence of oligoclonal bands and the close temporal relation to therapeutic apheresis. PMID- 26830689 TI - Species composition of sand flies and bionomics of Phlebotomus papatasi and P. sergenti (Diptera: Psychodidae) in cutaneous leishmaniasis endemic foci, Morocco. AB - BACKGROUND: Cutaneous Leishmaniasis (CL) is one of the most neglected tropical diseases in Morocco. Leishmania major and L. tropica are the main culprits identified in all endemic foci across the country. These two etiological agents are transmitted by Phlebotomus papatasi and P. sergenti, the two most prevalent sand fly species in Morocco. Previous studies reflected gaps of knowledge regarding the environmental fingerprints that affect the distribution of these two potential vectors across Morocco. METHODS: The sand flies were collected from 48 districts across Morocco using sticky paper traps. Collected specimens were preserved in 70% ethanol for further processing and identification. Male and female densities were calculated in each site to examine their relations to the environmental conditions across these sites. The study used 19 environmental variables including precipitation, aridity, elevation, soil variables and a composite representing maximum, minimum and mean of day- and night-time Land Surface Temperature (LST), and Normalized Difference Vegetation Index (NDVI). RESULTS: A total of 11,717 specimens were collected during this entomological survey. These specimens represented 11 species of two genera; Phlebotomus and Sergentomyia. Correlations of the sand fly densities with the environmental variables were estimated to identify the variables which influence the distribution of the two potential vectors, Phlebotomus papatasi and P. sergenti, associated with all CL endemic foci across the country. The density of P. papatasi was most affected by temperature changes. The study showed a significant positive correlation between the densities of both sexes of P. papatasi and night time temperatures. Both P. papatasi and P. sergenti showed a negative correlation with aridity, but, such correlation was only significant in case of P. papatasi. NDVI showed a positive correlation only with densities of P. sergenti, while, soil PH and soil water stress were negatively correlated with the densities of both males and females of only P. papatasi. CONCLUSIONS: Our results identified the sand fly species across all CL endemic sites and underlined the influences of night-time temperature, soil water stress and NDVI as the most important variables affecting the sand fly distribution in all sampled sites. This preliminary study considered the importance of these covariates to anticipate the potential distribution of P. papatasi and P. sergenti in Morocco. PMID- 26830690 TI - Comparison of open and endovascular treatment of patients with critical limb ischemia in the Vascular Quality Initiative. AB - OBJECTIVE: There is significant controversy in the management of critical limb ischemia (CLI) arising from infrainguinal peripheral arterial disease. We sought to compare practice patterns and perioperative and long-term outcomes for patients undergoing lower extremity bypass (LEB) and percutaneous vascular interventions (PVIs) for CLI in the Vascular Quality Initiative (VQI). METHODS: The prospectively collected VQI (2010-2013) LEB and PVI databases were retrospectively queried. Demographics, comorbidities, and perioperative outcomes were recorded. We evaluated all patients (cohort 1), those without comorbidities known to increase surgical risk (cohort 2) to control for patient factors, and patients with treatment anatomically limited to the superficial femoral artery (cohort 3) to control for anatomic factors. Multivariable analyses were performed to identify predictors of outcomes. RESULTS: There were 7897 patients with CLI and infrainguinal peripheral arterial disease, 4838 treated with PVI and 3059 with LEB. PVI patients had more comorbidities across all cohorts, whereas those undergoing LEB were more likely to have had a previous revascularization procedure. Follow-up at 1 year was 45.8% for PVI and 53.5% for LEB. After adjustment for comorbidities, cohort 1 patients treated with PVI vs LEB had lower odds of in-hospital or 30-day mortality (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.43-0.81; P = .001). This difference was not seen for the lower risk (cohort 2) patients (OR, 0.66; 95% CI, 0.39-1.14; P = .134) or the superficial femoral artery-only (cohort 3) patients (OR, 1.25; 95% CI, 0.53-2.96; P = .604). The 3-year mortality was higher with PVI in cohort 1 (HR, 1.23; 95% CI, 1.07-1.42; P = .003) and cohort 2 (HR, 1.63; 95% CI, 1.32-2.02; P < .001) but not cohort 3 (HR, 1.18; 95% CI, 0.82-1.71; P = .368). Amputation or death at 1 year was similar for PVI vs LEB in cohort 1 (HR, 0.98; 95% CI, 0.82-1.16; P = .816), cohort 2 (HR, 0.89; 95% CI, 0.7-1.15; P = .37), and cohort 3 (HR, 1.67; 95% CI, 0.86-3.2; P = .13). Major adverse limb event or death was lower for PVI at 1 year in cohort 1 (HR, 0.81; 95% CI, 0.72-0.91; P < .001) and cohort 2 (HR, 0.83; 95% CI, 0.71-0.97; P = .02) but not in cohort 3 (HR, 1.25; 95% CI, 0.85 1.84; P = .259). Length of stay for PVI was lower in all cohorts. CONCLUSIONS: In the VQI, PVI was more frequently offered to patients who were older and had more comorbidities, and LEB patients were more likely to have a history of previous interventions. Patients treated with PVI had lower perioperative mortality overall, although this benefit was not seen when treating patients with fewer comorbidities or less advanced disease. However, PVI patients had higher adjusted 3-year mortality in the overall sample and in lower-risk patients. Limitations to this study, especially the follow-up, hamper meaningful interpretation of reinterventions and further reinforce the need for large, randomized, clinical studies with better long-term follow-up. PMID- 26830691 TI - Simvastatin pretreatment enhances ischemia-induced neovascularization and blood flow recovery in streptozotocin-treated mice. AB - OBJECTIVE: In contrast to statins, ezetimibe belongs to a new class of cholesterol-lowering agent not known to mediate pleiotropic effects. Here we investigate whether ezetimibe or simvastatin can help recover blood flow and reduce tissue damage after hindlimb ischemia surgery in diabetic mice. METHODS: Diabetic mice were created by intraperitoneal streptozotocin injection in male FVB/NJ mice. All diabetic mice were subsequently divided into three groups: diabetic control, diabetic with simvastatin (0.2 mg/kg), and diabetic with ezetimibe (0.1 mg/kg). All experimental mice received hindlimb ischemia surgery after 2 weeks of drug treatment. Circulating endothelial progenitor cell number was determined by flow cytometry (Sca-1+/C-kit+/Flk-1+) in peripheral blood. RESULTS: In comparison to the mice in the diabetic control group (n = 6), wild type mice (n = 6) and diabetic mice that received simvastatin (n = 6) had significantly increased ischemic/nonischemic limb blood perfusion ratio, higher capillary density (P < .05, respectively), and reduced ischemic limb damage (diabetic control, 80%; diabetic with simvastatin, 40%; diabetic with ezetimibe, 80%). However, these proangiogenic effects were not observed in diabetic mice that had been treated with ezetimibe. In addition, the number of ischemia triggered endothelial progenitor cells in peripheral blood was significantly enhanced in the wild-type mice and in the diabetic mice being treated with simvastatin, but not in those being treated with ezetimibe, after ischemic surgery. Endothelial nitric oxide synthase activity as determined by acetylcholine-stimulated vasorelaxation recovered notably in diabetic mice that were treated with simvastatin but was not improved by ezetimibe (n = 6, each group). Moreover, simvastatin led to a significant upregulation of endothelial nitric oxide synthase phosphorylation; vascular endothelial growth factor protein levels in ischemic tissues were also increased. By contrast, administration of ezetimibe did not produce these effects. CONCLUSIONS: Simvastatin helped recover blood flow and reduce tissue damage in ischemic hindlimbs and also promoted new vessel formation in streptozotocin-treated mice, whereas ezetimibe did not. These results may help explain why statins and ezetimibe decrease cholesterol levels, whereas their pleiotropic effects on vasoprotective functions independent of low density lipoprotein cholesterol lowering are different. PMID- 26830692 TI - The Financial Associations of Public Speakers at Meetings of Federal Health Advisory Committees. PMID- 26830693 TI - Impact of imputation methods on the amount of genetic variation captured by a single-nucleotide polymorphism panel in soybeans. AB - BACKGROUND: Success in genome-wide association studies and marker-assisted selection depends on good phenotypic and genotypic data. The more complete this data is, the more powerful will be the results of analysis. Nevertheless, there are next-generation technologies that seek to provide genotypic information in spite of great proportions of missing data. The procedures these technologies use to impute genetic data, therefore, greatly affect downstream analyses. This study aims to (1) compare the genetic variance in a single-nucleotide polymorphism panel of soybean with missing data imputed using various methods, (2) evaluate the imputation accuracy and post-imputation quality associated with these methods, and (3) evaluate the impact of imputation method on heritability and the accuracy of genome-wide prediction of soybean traits. The imputation methods we evaluated were as follows: multivariate mixed model, hidden Markov model, logical algorithm, k-nearest neighbor, single value decomposition, and random forest. We used raw genotypes from the SoyNAM project and the following phenotypes: plant height, days to maturity, grain yield, and seed protein composition. RESULTS: We propose an imputation method based on multivariate mixed models using pedigree information. Our methods comparison indicate that heritability of traits can be affected by the imputation method. Genotypes with missing values imputed with methods that make use of genealogic information can favor genetic analysis of highly polygenic traits, but not genome-wide prediction accuracy. The genotypic matrix captured the highest amount of genetic variance when missing loci were imputed by the method proposed in this paper. CONCLUSIONS: We concluded that hidden Markov models and random forest imputation are more suitable to studies that aim analyses of highly heritable traits while pedigree-based methods can be used to best analyze traits with low heritability. Despite the notable contribution to heritability, advantages in genomic prediction were not observed by changing the imputation method. We identified significant differences across imputation methods in a dataset missing 20 % of the genotypic values. It means that genotypic data from genotyping technologies that provide a high proportion of missing values, such as GBS, should be handled carefully because the imputation method will impact downstream analysis. PMID- 26830694 TI - Multi-criteria optimization achieves superior normal tissue sparing in a planning study of intensity-modulated radiation therapy for RTOG 1308-eligible non-small cell lung cancer patients. AB - PURPOSE: In this planning study, we studied the benefit of intensity-modulated radiation therapy (IMRT) with multi-criteria optimization (MCO) in locally advanced non-small cell lung carcinoma (NSCLC). METHODS: We selected 10 consecutive patients with gross tumor within 1cm of the esophagus eligible for RTOG 1308, randomized phase II trial of 70 Gy protons vs photons. Planning was performed per protocol. In addition, a novel approach for esophagus sparing was applied by making the contralateral esophagus (CE) an avoidance structure. MCO and non-MCO plans underwent double-blinded review. Plan differences in dose volume histogram parameters were analyzed. RESULTS: Median plan differences were mean lung dose=0.8 Gy (p=0.01), lung V20=1.1% (p=0.06), heart V30=1.0% (p=0.03), heart V45=0.6% (p=0.03), esophagus V60=1.2% (p=0.04), and CE V45=3.2% (p=0.01), all favoring MCO over non-MCO. PTV coverage with 95% dose was ?98.0% for both plans. There were 5 minor protocol deviations with non-MCO plans and 2 with MCO. Median improvement of active planning time with MCO was 88 min (p<0.01). Physicians preferred 8 MCO and 2 non-MCO plans (p=0.04). CONCLUSIONS: MCO plans yielded significant improvements in organ-at-risk sparing without compromising target coverage, consumed less dosimetrist time, and were preferred by physicians. We suggest incorporating MCO into prospective clinical trials. PMID- 26830695 TI - Clinical impact of combined transarterial chemoembolization and radiotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: An external validation study. AB - PURPOSE: To evaluate the relationship between portal vein tumor thrombosis (PVTT) response and clinical outcomes in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization followed by radiotherapy (TACE-RT). MATERIALS AND METHODS: The study enrolled 329 patients in the training set and 179 patients in the validation set. All patients who were treated with TACE-RT from 2002 to 2008 and satisfied the inclusion criteria were enrolled in the study. The median follow-up period was 11.7 months (range, 1.6-108.6) in the training set and 11.9 months (range, 1.7-105.1) in the validation set. RESULTS: After TACE-RT, PVTT response was complete or partial in 32 (9.7%) and 134 (40.7%) patients of the training set and in 18 (10.1%) and 96 (53.6%) patients in the validation set, respectively. Failure to obtain PVTT response was significantly related with elevated post-treatment Child-Pugh score (P<0.001). Furthermore, progression-free survival was significantly related with PVTT response (P<0.001, hazard ratio 0.33, 95% confidence interval 0.25-0.42) in multivariate analysis. In receiver-operating characteristics analysis of 1-year progression prediction, the PVTT response showed an area under the curve of 0.74. Most of the findings were successfully reproduced in the independent external validation set. CONCLUSIONS: Positive PVTT response was closely associated with favorable clinical outcomes. The PVTT response to TACE-RT reduces metastasis and makes it possible to maintain normal liver function and achieve longer survival. PMID- 26830696 TI - Quantification of respiration-induced esophageal tumor motion using fiducial markers and four-dimensional computed tomography. AB - BACKGROUND AND PURPOSE: Respiration-induced tumor motion is an important geometrical uncertainty in esophageal cancer radiation therapy. The aim of this study was to quantify this motion using fiducial markers and four-dimensional computed tomography (4DCT). MATERIALS AND METHODS: Twenty esophageal cancer patients underwent endoscopy-guided marker implantation in the tumor volume and 4DCT acquisition. The 4DCT data were sorted into 10 breathing phases and the end of-inhalation phase was selected as reference. We quantified for each visible marker (n=60) the motion in each phase and derived the peak-to-peak motion magnitude throughout the breathing cycle. The motion was quantified and analyzed for four different regions and in three orthogonal directions. RESULTS: The median(interquartile range) of the peak-to-peak magnitudes of the respiration induced marker motion (left-right/anterior-posterior/cranial-caudal) was 1.5(0.5)/1.6(0.5)/2.9(1.4) mm for the proximal esophagus (n=6), 1.5(1.4)/1.4(1.3)/3.7(2.6) mm for the middle esophagus (n=12), 2.6(1.3)/3.3(1.8)/5.4(2.9) mm for the distal esophagus (n=25), and 3.7(2.1)/5.3(1.8)/8.2(3.1) mm for the proximal stomach (n=17). CONCLUSIONS: The variations in the results between the three directions, four regions, and patients suggest the need of individualized region-dependent anisotropic internal margins. Therefore, we recommend using markers with 4DCT to patient-specifically adapt the internal target volume (ITV). Without 4DCT, 3DCTs at the end-of inhalation and end-of-exhalation phases could be alternatively applied for ITV individualization. PMID- 26830698 TI - Is an unhealthy work environment in nursing home care for people with dementia associated with the prescription of psychotropic drugs and physical restraints? AB - BACKGROUND: Research showed that long-term care facilities differ widely in the use of psychotropic drugs and physical restraints. The aim of this study is to investigate whether characteristics of an unhealthy work environment in facilities for people with dementia are associated with more prescription of psychotropic drugs and physical restraints. METHODS: Data were derived from the first wave (2008-2009) of a national monitoring study in the Netherlands. This paper used data on prescription of psychotropic drugs and physical restraints from 111 long-term care facilities, residing 4,796 residents. Survey data of a sample of 996 staff and 1,138 residents were considered. The number of residents with prescribed benzodiazepines and anti-psychotic drugs, and physical restraints were registered. Work environment was assessed using the Leiden Quality of Work Questionnaire (LQWQ). RESULTS: Logistic regression analyses showed that more supervisor support was associated with less prescription of benzodiazepines. Coworker support was found to be related to less prescription of deep chairs. Job demands and decision authority were not found to be predictors of psychotropic drugs and physical restraints. CONCLUSIONS: Staff's job characteristics were scarcely related to the prescription of psychotropic drugs and physical restraints. This finding indicates that in facilities with an unhealthy work environment for nursing staff, one is not more likely to prescribe drugs or restraints. Further longitudinal research is needed with special attention for multidisciplinary decision making - especially role of physician, staff's knowledge, philosophy of care and institutional policy to gain further insight into factors influencing the use of psychotropic drugs and restraints. PMID- 26830697 TI - Magnetic resonance imaging of swallowing-related structures in nasopharyngeal carcinoma patients receiving IMRT: Longitudinal dose-response characterization of quantitative signal kinetics. AB - BACKGROUND: We aim to characterize serial (i.e., acute and late) MRI signal intensity (SI) changes in dysphagia-associated structures as a function of radiotherapy (RT) in nasopharyngeal cancer (NPC) patients. MATERIALS AND METHODS: We retrospectively extracted data on 72 patients with stage III-IV NPC treated with intensity-modulated RT (IMRT). The mean T1- and T2-weighted MRI SIs were recorded for the superior pharyngeal constrictor (SPC) and soft palate (SP) at baseline, early-after IMRT, and last follow up, with normalization to structures receiving <5 Gy. RESULTS: All structures had a significant increase in T2 SIs early after treatment, irrespective of the mean dose given. At last follow-up, the increase in T2 SI subsided completely for SPC and partially for SP. The T1 SI did not change significantly in early follow-up images of both structures; on late follow-up, patients with mean doses >62.25 Gy had a significant decrease in the corresponding T1 SI for SPC (1.6 +/- 0.4 vs. 1.3 +/- 0.4, P=0.007) but decreased non-significantly for SP. CONCLUSIONS: Serial MRI acquisitions enable the identification of both early and late radiation-induced changes in swallowing structures after definitive IMRT for NPC. Dose dependent decrease in late T1 SI is associated with higher RT doses to the superior pharyngeal constrictor muscle; while dose independent increase in SI for both structures in early post-RT T2 images is observed and subsides after therapy. Further efforts will seek to elucidate the relationship between dose-dependent muscle SI changes and functional alteration of swallowing muscles. PMID- 26830699 TI - Reconsidering great ape imitation and pantomime: Comment on "Towards a Computational Comparative Neuroprimatology: framing the language-ready brain" by Michael A. Arbib. PMID- 26830700 TI - Accommodating 'unaccustomed pragmatic spaces' in Arbib's model Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael A. Arbib. PMID- 26830701 TI - Boltzmann equation modelling of Learning Dynamics: Comment on "Collective learning modeling based on the kinetic theory of active particles" by D. Burini et al. PMID- 26830702 TI - Engineered embodiment: Comment on "The embodiment of assistive devices-from wheelchair to exoskeleton" by M. Pazzaglia and M. Molinari. PMID- 26830703 TI - The cultural evolution of language and brain: Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael A. Arbib. PMID- 26830704 TI - Embodying prostheses - how to let the body welcome assistive devices: Comment on "The embodiment of assistive devices-from wheelchair to exoskeleton" by M. Pazzaglia and M. Molinari. PMID- 26830705 TI - Dual-stream accounts bridge the gap between monkey audition and human language processing: Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael Arbib. PMID- 26830707 TI - Smooth pursuit eye movements in patients with macular degeneration. AB - Currently, there are no quantitative studies of smooth pursuit, a behavior attributed to the fovea, in individuals with macular degeneration (MD). We hypothesize that pursuit in MD patients depends on the relative positions of the scotoma and target trajectory. We tested this hypothesis with a scanning laser ophthalmoscope (SLO), which allows for direct visualization of the target on the damaged retina. Monocular microperimetry and eye movements were assessed in eleven individuals with differing degrees of MD. Observers were asked to visually track a 1.7 degrees target that moved in one of eight radial directions at 5 degrees /s-6 degrees /s. Consistent with our hypothesis, pursuit metrics depended on whether the target moved into or out of scotoma. Pursuit gains decreased with increasing scotoma extent in the target's heading direction (p = 0.017). Latencies were higher when the scotoma was present along the target trajectory (in either starting or heading directions, p < 0.001). Furthermore, an analysis of retinal position shows that targets fell on the fixational locus nearly 50% of the time. The results suggest that MD patients are capable of smooth pursuit eye movements, but are limited by target trajectory and scotoma characteristics. PMID- 26830708 TI - Gaze-dependent phoria and vergence adaptation. AB - Incomitance is a condition with gaze-dependent deviations of ocular alignment and is common in strabismus patients. The physiological mechanisms that maintain equal horizontal ocular alignment in all gaze directions (concomitance) in healthy individuals are poorly explored. We investigate adaptive processes in the vergence system that are induced by horizontal incomitant vergence stimuli (stimuli that require a gaze-dependent vergence response in order to re-establish binocular single vision). We measured horizontal vergence responses elicited after healthy subjects shifted their gaze from a position that required no vergence to a position that required convergence. Repetitive saccades into a position with a convergence stimulus rapidly decreased phoria (defined as the deviation of ocular alignment in the absence of a binocular stimulus). This change of phoria was present in all viewing directions (from 0 degrees to 0.86 degrees +/- 0.40 degrees , p < 0.001) but was more pronounced in the gaze direction with a convergence stimulus (from 0.26 degrees +/- 0.13 degrees to 1.39 degrees +/- 0.33 degrees , p < 0.001). We also found that vergence velocity rapidly increased (p = 0.015) and vergence latency promptly decreased (p < 0.001). We found gaze-dependent modulation of phoria in combined saccade-vergence eye movements and also in pursuit-vergence eye movements. Thus, acute horizontal, gaze-dependent changes of vergence, such as may be encountered in new onset strabismus due to paralysis, can rapidly increase vergence velocity and decrease latency. Gaze-specific (concomitant) and gaze-independent (incomitant) phoria levels will adapt. These early adaptive processes increase the efficacy of binocular vision and maintain good ocular alignment in all directions of gaze. PMID- 26830709 TI - Incidental statistical summary representation over time. AB - Information taken in by the human visual system allows individuals to form statistical representations of sets of items. One's knowledge of natural categories includes statistical information, such as average size of category members and the upper and lower boundaries of the set. Previous research suggests that when subjects attend to a particular dimension of a set of items presented over an extended duration, they quickly learn about the central tendency of the set. However, it is unclear whether such learning can occur incidentally, when subjects are not attending to the relevant dimension of the set. The present study explored whether subjects could reproduce global statistical properties of a set presented over an extended duration when oriented to task-irrelevant properties of the set. Subjects were tested for their memory of its mean, its smallest and largest exemplars, the direction of its skew, and the relative distribution of the items. Subjects were able to accurately recall the average size circle, as well as the upper and lower boundaries of a set of 4,200 circles displayed over an extended period. This suggests that even without intending to do so, they were encoding and updating a statistical summary representation of a task-irrelevant attribute of the circles over time. Such incidental encoding of statistical properties of sets is thus a plausible mechanism for establishing a representation of typicality in category membership. PMID- 26830706 TI - Contextualising primate origins--an ecomorphological framework. AB - Ecomorphology - the characterisation of the adaptive relationship between an organism's morphology and its ecological role - has long been central to theories of the origin and early evolution of the primate order. This is exemplified by two of the most influential theories of primate origins: Matt Cartmill's Visual Predation Hypothesis, and Bob Sussman's Angiosperm Co-Evolution Hypothesis. However, the study of primate origins is constrained by the absence of data directly documenting the events under investigation, and has to rely instead on a fragmentary fossil record and the methodological assumptions inherent in phylogenetic comparative analyses of extant species. These constraints introduce particular challenges for inferring the ecomorphology of primate origins, as morphology and environmental context must first be inferred before the relationship between the two can be considered. Fossils can be integrated in comparative analyses and observations of extant model species and laboratory experiments of form-function relationships are critical for the functional interpretation of the morphology of extinct species. Recent developments have led to important advancements, including phylogenetic comparative methods based on more realistic models of evolution, and improved methods for the inference of clade divergence times, as well as an improved fossil record. This contribution will review current perspectives on the origin and early evolution of primates, paying particular attention to their phylogenetic (including cladistic relationships and character evolution) and environmental (including chronology, geography, and physical environments) contextualisation, before attempting an up to-date ecomorphological synthesis of primate origins. PMID- 26830710 TI - Molecular and phenotypic characteristics of seven novel mutations causing branched-chain organic acidurias. AB - Specific mitochondrial enzymatic deficiencies in the catabolism of branched-chain amino acids cause methylmalonic aciduria (MMA), propionic acidemia (PA) and maple syrup urine disease (MSUD). Disease-causing mutations were identified in nine unrelated branched-chain organic acidurias (BCOA) patients. We detected eight previously described mutations: p.Asn219Tyr, p.Arg369His p.Val553Glyfs*17 in MUT, p.Thr198Serfs*6 in MMAA, p.Ile144_Leu181del in PCCB, p.Gly288Valfs*11, p.Tyr438Asn in BCKDHA and p.Ala137Val in BCKDHB gene. Interestingly, we identified seven novel genetic variants: p.Leu549Pro, p.Glu564*, p.Leu641Pro in MUT, p.Tyr206Cys in PCCB, p.His194Arg, p.Val298Met in BCKDHA and p.Glu286_Met290del in BCKDHB gene. In silico and/or eukaryotic expression studies confirmed pathogenic effect of all novel genetic variants. Aberrant enzymes p.Leu549Pro MUT, p.Leu641Pro MUT and p.Tyr206Cys PCCB did not show residual activity in activity assays. In addition, activity of MUT enzymes was not rescued in the presence of vitamin B12 precursor in vitro which was in accordance with non-responsiveness or partial responsiveness of patients to vitamin B12 therapy. Our study brings the first molecular genetic data and detailed phenotypic characteristics for MMA, PA and MSUD patients for Serbia and the whole South Eastern European region. Therefore, our study contributes to the better understanding of molecular landscape of BCOA in Europe and to general knowledge on genotype-phenotype correlation for these rare diseases. PMID- 26830711 TI - Catch me if you can...early simulation efforts affect fundamental surgical skill assessment scores. AB - BACKGROUND: We evaluated whether early exposure to a simulation curriculum enhances acquired surgical skills. METHODS: The "Surgical Olympics" evaluates interns on basic surgical skills and knowledge. After the Summer Olympics (July), interns were randomly divided into groups: "A" participated in a 7-week curriculum once a week, whereas "B" attended 7 weeks of lectures once a week. All interns then participated in the October Olympics. The 2 groups then switched. Finally, all interns completed a January Olympics. RESULTS: Scores were tabulated for the July, October, and January Olympics. Mean scores (A = 182 +/- 42, Group B = 188 +/- 34; P = .70) were similar in July; in October, group A (mean score = 237 +/- 31) outperformed group B (mean score = 200 +/- 32; P = .01). Mean total scores in January (A = 290 +/- 34, B = 276 +/- 34; P = .32) were similar. CONCLUSIONS: Early exposure to a surgical simulation curriculum enhances surgical intern performance in our Surgical Olympics. Subsequent simulation experience helps learners close this gap. PMID- 26830712 TI - Intraductal papillary mucinous neoplasm of the pancreas, one manifestation of a more systemic disease? AB - BACKGROUND: Several studies have demonstrated a high prevalence of extrapancreatic malignancies, and an association with autoimmune pancreatitis in patients with intraductal papillary mucinous neoplasm (IPMN). We hypothesized that IPMNs were associated with an increase rate of systemic diseases. METHODS: From 1996 to 2013, a retrospective analysis of a prospectively collected database was performed and supplemented with electronic medical charts review. RESULTS: Two hundred twenty extrapancreatic malignancies were found in 185 patients (22%) compared with expected 5% in the general population. Colorectal, lung, and renal cell carcinoma had significant observed/expected ratios (P < .0001). One hundred ten synchronous autoimmune diseases were found in 96 patients (11%). Systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease showed statistically significant observed/expected ratios (P < .0001, .01, and <.0001, respectively). There was no impact of immunosuppressive treatment on the IPMN subtype and malignancy rate. CONCLUSIONS: IPMN are associated with surprisingly high rates of autoimmune diseases suggesting that IPMN might be 1 manifestation of a more systemic disease. PMID- 26830713 TI - Surgery clerkship orientation: evaluating temporal changes in student orientation needs. AB - BACKGROUND: Surgery clerkship students at our institution receive a standardized orientation covering objectives, requirements, grading, and expectations. Limited data exist regarding the student perceptions of this approach. METHODS: Surveys were provided to students to rate the importance of orientation topics and their satisfaction with topic conclusion. Scores between student groupings over the clerkship year were analyzed with Student t tests and analysis of variance with Scheffe adjustments. RESULTS: Significant differences in the mean importance rating between topics exists (P < .0001) as well as among satisfaction scores for topics (P < .0005). Early clerkship students value course expectations higher than later students (P = .03). Early clerkship students want more time devoted to hospital tours and expectations compared with later students (31% vs 8%). CONCLUSIONS: Orientation needs for students change over the clerkship year. Beginning students prefer basic direction for time spent on the ward. Later students prefer information regarding shelf preparation. Surgery course directors can adapt the orientation based on the experience of clerkship students. PMID- 26830714 TI - Postdischarge complications following nonoperative management of blunt splenic injury. AB - BACKGROUND: Nonoperative management (NOM) is the standard of care in majority of blunt splenic injuries. However, little is known about the postdischarge complications. METHODS: Patients admitted for blunt splenic injury were identified in the California State Inpatient Database (2007 to 2011). We examined patterns and risk factors for postdischarge complications among these patients. RESULTS: In total, 2,704 (61.45%) patients had NOM without splenic artery embolization (SAE) and 257 (5.84%) had NOM with adjunct SAE. Thirty-day readmission rate was higher in those who had adjunct SAE (12.84% vs 7.36%, P = .002). Subsequent operations during readmission were seen in 18.10% of readmitted patients and 38.10% of all patients were readmitted at nonindex hospitals. Major diagnoses on readmission were spleen injury (36.2%) and respiratory complications (9.05%). Adjunct SAE was an independent risk factor for readmission (adjusted odds ratio 1.82, 95% confidence interval 1.19 to 2.78). CONCLUSIONS: Nearly one fifth of readmitted patients initially managed nonoperatively required an operative intervention. Improving predischarge assessments and postdischarge follow-up may reduce readmissions among these patients. PMID- 26830715 TI - Is fear for postoperative cardiopulmonary complications after bariatric surgery in patients with obstructive sleep apnea justified? A systematic review. AB - BACKGROUND: To evaluate the influence of obstructive sleep apnea (OSA) on postoperative cardiopulmonary complications in bariatric surgery patients. METHODS: PubMed, Embase, and the Cochrane central register databases were searched. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was used for reviewing. RESULTS: Thirteen studies were included (n = 98,935). OSA was documented in 36,368 (37%) patients. The cardiopulmonary complication rate varied between .0% and 25.8%; no clear association with OSA was found (rate .0% to 18%), possibly because of optimized situations such as continuous positive airway pressure. OSA appeared to be no independent risk factor for intensive care unit (ICU) admission, death, or longer length of stay in most studies. CONCLUSIONS: Overall, presented data showed no clear association of OSA with cardiopulmonary morbidity, ICU admissions, mortality, and length of stay after bariatric surgery. Although this questions the justification of admitting OSA patients to the ICU, future studies are required investigating the effect of monitoring strategies and optimizing treatments including continuous positive airway pressure use. PMID- 26830716 TI - Spindle cell carcinoma of the breast: a comprehensive analysis. AB - BACKGROUND: Breast spindle cell malignancies are rare. No standard treatment exists. METHODS: The Surveillance, Epidemiology, and End Results database was used to identify patients with breast spindle cell malignancies, 1992 to 2011. Descriptive statistical analysis and survival analysis were performed. RESULTS: A total of 286 patients were identified (98.6% female). Approximately, 15% had estrogen receptor-positive tumors and 12.5% had progesterone receptor-positive tumors. Nearly 38% underwent partial mastectomy, whereas 55.5% underwent mastectomy. The frequency of partial mastectomy has increased in more recent years. One-third received radiation. Lymph node metastases were infrequent (9.3%) and distant metastases were uncommon (6.1%). Ten-year survival rates for patients with early-stage (I and II) disease were 83.9% after partial mastectomy, 86.7% after partial mastectomy plus radiation, and 71.6% after complete mastectomy. Three-year survival rates for patients with late-stage (III and IV) disease were low with 40.0% after complete mastectomy and 0% after complete mastectomy plus radiation. CONCLUSIONS: This nationally representative analysis demonstrates that early-stage spindle cell carcinoma of the breast is adequately treated by partial mastectomy. Radiation may be considered for small, potentially early survival benefit. For late stage disease, complete mastectomy is appropriate; however, survival is poor, and radiation contributes no significant additional benefit. PMID- 26830717 TI - Postoperative outcomes of major lower extremity amputations in patients with diabetes and peripheral artery disease: analysis using the Diagnosis Procedure Combination database in Japan. AB - BACKGROUND: The purpose of the present study was to investigate 30-day postoperative outcomes after lower extremity amputation in patients with diabetes mellitus (DM) alone, peripheral artery disease (PAD) alone, or both. METHODS: Eight thousand five hundred sixty-five patients with DM alone (n = 2,700), PAD alone (n = 2,919), and both (n = 2,946) who had above-knee amputation or below knee amputation during 2007 to 2012 from the Japanese Diagnosis Procedure Combination inpatient database were retrospectively analyzed. RESULTS: Overall 30 day mortality was 6.4% (5.1%, 8.5%, and 5.6% in DM alone, PAD alone and both group, respectively). Multivariable regression analysis showed no significant differences in 30-day mortality or overall postoperative complication rates among the 3 groups. Patients with both PAD and DM had a significantly higher proportion of cardiac events than those with DM alone (6.9% vs 3.0%; odds ratio = 2.27; 95% confidence interval = 1.73 to 2.98). CONCLUSIONS: Patients with both DM and PAD were more likely to have postoperative cardiac events. PMID- 26830718 TI - Procedural volume and survival after lung transplantation in the United States: the need to look beyond volume in the establishment of quality metrics. AB - BACKGROUND: We sought to evaluate the effect of center volume on patient survival. METHODS: We performed a retrospective analysis on nationwide data from the Scientific Registry of Transplant Recipients provided by United Network for Organ Sharing pertaining to lung transplantation (LT) recipients transplanted between 2005 and 2013. Centers were categorized into 4 groups based on their annual volume as follows: less than 20, 20 to 29, 30 to 39, and greater than or equal to 40 LTs. Baseline characteristics were compared and Kaplan-Meier analysis was used to estimate survival. RESULTS: A total of 13,506 adult recipients underwent LT during the study period. Of these, 2,491 (18.4%) patients were transplanted in centers with volume less than 20, 2,562 (19.0%) in centers with volume 20 to 29, 2,998 (22.2%) in centers with volume 30 to 39, and 5,455(40.4%) in centers with volume greater than or equal to 40. Survival was poorest in the lowest volume centers (1-year 81.4% vs 85.5% and 5-year 49.7% vs 56.5%, respectively). CONCLUSIONS: Post-LT survival in low volume centers is significantly lower than in high volume centers but the explanatory power of volume as a predictor of survival is low. PMID- 26830719 TI - Patency of the Viabahn stent graft for the treatment of outflow stenosis in hemodialysis grafts. AB - BACKGROUND: To evaluate arteriovenous graft patency when failing grafts are treated with Viabahn covered stents vs percutaneous angioplasty (PTA) alone. METHODS: A retrospective review of all patients that underwent endovascular interventions for failing grafts at a single institution between January 2010 and July 2013 was performed. Forty-four patients were identified who were treated with PTA alone (11) and with Viabahn stent grafts (33) for stenoses in the venous to graft anastomoses. Patient demographics, procedural success, and intraoperative complications were recorded as well as graft patency at 3, 6, and 12 months. Graft patency was reviewed and compared with PTA alone. RESULTS: There was no statistically significant difference between the 2 groups regarding gender, frequency of diabetes, hypertension, coronary artery disease, or peripheral arterial disease. Primary technical success defined as residual stenosis 10% or less was achieved in 100% of the cases. Follow-up was determined by flow velocities during dialysis and ultrasound imaging in the vascular laboratory. At 12 months 87.8% (29/33) grafts with stents were functional vs 36.4% (4/11) of those with PTA alone. Primary patency of the stent group was 61%, 52%, and 42% at 3, 6, and 12 months respectively vs the PTA group 64%, 45%, and 9%. CONCLUSIONS: Grafts treated with Viabahn covered stents for outflow stenosis have a superior patency to PTA alone, 12 months after treatment; although earlier post treatment results are comparable. PMID- 26830721 TI - Echocardiographic Diagnosis of Ventricular Tachycardia: Is There a Problem With Clinical and Electrocardiographic Diagnostic Criteria? Response. PMID- 26830720 TI - Survival and Neurologic Outcome After Out-of-hospital Cardiac Arrest. Results of the Andalusian Out-of-hospital Cardiopulmonary Arrest Registry. AB - INTRODUCTION AND OBJECTIVES: There is a paucity of data on prehospital cardiac arrest in Spain. Our aim was to describe the incidence, patient characteristics, and outcomes of out-of-hospital emergency care for this event. METHODS: We conducted a retrospective analysis of a prospective registry of cardiopulmonary arrest handled by an out-of-hospital emergency service between January 2008 and December 2012. The registry included all patients considered to have a cardiac etiology as the cause of arrest, with a descriptive analysis performed of general patient characteristics and factors associated with good neurologic outcome at hospital discharge. RESULTS: A total of 4072 patients were included, with an estimated incidence of 14.6 events per 100000 inhabitants and year; 72.6% were men. The mean age was 62.0 +/- 15.8 years, 58.6% of cases occurred in the home, 25% of patients had initial defibrillable rhythm, 28.8% of patients arrived with a pulse at the hospital (58.3% of the group with defibrillable rhythm), and 10.2% were discharged with good neurologic outcome. The variables associated with this recovery were: witnessed arrest (P=.04), arrest witnessed by emergency team (P=.005), previous life support (P=.04), initial defibrillable rhythm (P=.0001), and performance of a coronary interventional procedure (P=.0001). CONCLUSIONS: More than half the cases of sudden cardiac arrest occur at home, and the population was found to be relatively young. Although recovery was satisfactory in 1 out of every 10 patients, there is a need for improvement in the phase prior to emergency team arrival. Coronary interventional procedures had an impact on patient prognosis. PMID- 26830722 TI - Subcutaneous Defibrillator: Role in the Prevention of Sudden Cardiac Death in the Setting of Mechanical Tricuspid Prosthesis. PMID- 26830723 TI - Echocardiographic Diagnosis of Ventricular Tachycardia: Is There a Problem With Clinical and Electrocardiographic Diagnostic Criteria? PMID- 26830724 TI - Role of Hydrogen Sulfide in Systemic and Pulmonary Hypertension: Cellular Mechanisms and Therapeutic Implications. AB - There is increasing interest in the possible therapeutic benefits of the gasotransmitter hydrogen sulfide (H2S sulfide), and drugs which release sulfide are currently being evaluated in both preclinical and clinical studies as treatments for conditions ranging from cancer to cardiovascular disease to inflammation. Sulfide is generally considered to act as a vasodilator, and it is therefore not surprising that the effects of sulfide donors on both systemic and pulmonary hypertension are being examined. In this review, we provide a critical evaluation of both the evidence that H2S may be of benefit in treating systemic and pulmonary hypertension, and of current hypotheses regarding the cellular mechanisms underlying sulfide's effects on the systemic and pulmonary vascular systems. PMID- 26830725 TI - [Negative Pressure Wound Therapy (NPWT) in small animal medicine. Mechanisms of action, applications and indications]. AB - The treatment of open wounds is a daily challenge in veterinary medicine. During the past years, a special treatment option, the Negative Pressure Wound Therapy (NPWT), has been developed. Usage of this therapy significantly increases the healing rate of open wounds as well as free skin grafts in small animals. This review describes the mechanisms of action, indications as well as the known complications associated with this therapy. PMID- 26830727 TI - Myxozoa + Polypodium: A Common Route to Endoparasitism. AB - Recent evidence places the problematic Polypodium, a parasite of fish eggs, firmly as sister taxon to Myxozoa within the Cnidaria. This resolution suggests a single route to endoparasitism in Cnidaria, with larval stages of a common ancestor exploiting fish as first hosts. It also enables new interpretations and insights regarding evolutionary transitions associated with endoparasitism. PMID- 26830726 TI - All For One and One For All on the Tick-Host Battlefield. AB - The saliva of ixodid ticks contains a mixture of bioactive molecules that target a wide spectrum of host defense mechanisms to allow ticks to feed on the vertebrate host for several days. Tick salivary proteins cluster in multigenic protein families, and individual family members display redundancy and pluripotency in their action to ameliorate or evade host immune responses. It is now clear that members of different protein families can target the same cellular or molecular pathway of the host physiological response to tick feeding. We present and discuss our hypothesis that redundancy and pluripotency evolved in tick salivary immunomodulators to evade immune recognition by the host while retaining the immunomodulatory potential of their saliva. PMID- 26830728 TI - Editorial: Preventing postoperative ileus with n-3 PUFA. PMID- 26830729 TI - Editorial: Fish neutrophils meet proresolving eicosanoids. PMID- 26830730 TI - Does the Hippocampus Map Out the Future? AB - Decades of research have established two central roles of the hippocampus--memory consolidation and spatial navigation. Recently, a third function of the hippocampus has been proposed: simulating future events. However, claims that the neural patterns underlying simulation occur without prior experience have come under fire in light of newly published data. PMID- 26830731 TI - Associating liver partition and portal vein ligation for staged hepatectomy in patients with colorectal liver metastases--Intermediate oncological results. AB - BACKGROUND: Colorectal liver metastases (CRLM) not amenable for resection have grave prognosis. One limiting factor for surgery is a small future liver remnant (FLR). Early data suggests that associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) effectively increases the volume of the FLR allowing for resection in a larger fraction of patients than conventional two stage hepatectomy (TSH) with portal vein occlusion (PVO). Oncological results of the treatment are lacking. The aim of this study was to assess the intermediate oncological outcomes after ALPPS in patients with CRLM. MATERIAL AND METHODS: Retrospective analysis of all patients with CRLM operated with ALPPS at the participating centres between December 2012 and May 2014. RESULTS: Twenty-three patients (16 male, 7 female), age 67 years (28-80) were operated for 6.5 (1-38) metastases of which the largest was 40 mm (14-130). Six (27.3%) patients had extra-hepatic metastases, 16 (72.7%) synchronous presentation. All patients received chemotherapy, 6 cycles (3-25) preoperatively and 16 (70%) postoperatively. Ten patients (43%) were rescue ALPPS after failed PVO. Severe complications occurred in 13.6% and one (4.5%) patient died within 90 days of surgery. After a median follow-up of 22.5 months from surgery and 33.5 months from diagnosis of liver metastases estimated 2 year overall survival was 59% (from surgery) and 73% (from diagnosis). Liver only recurrences (n = 8), were treated with reresection/ablation (n = 7) while lung recurrences were treated with chemotherapy. CONCLUSION: The overall survival, rate of severe complications and perioperative mortality associated with ALPPS for patients with CRLM is comparable to TSH. PMID- 26830732 TI - Three-dimensional porous carbon composites containing high sulfur nanoparticle content for high-performance lithium-sulfur batteries. AB - Sulfur is a promising cathode material for lithium-sulfur batteries because of its high theoretical capacity (1,675 mA h g(-1)); however, its low electrical conductivity and the instability of sulfur-based electrodes limit its practical application. Here we report a facile in situ method for preparing three dimensional porous graphitic carbon composites containing sulfur nanoparticles (3D S@PGC). With this strategy, the sulfur content of the composites can be tuned to a high level (up to 90 wt%). Because of the high sulfur content, the nanoscale distribution of the sulfur particles, and the covalent bonding between the sulfur and the PGC, the developed 3D S@PGC cathodes exhibit excellent performance, with a high sulfur utilization, high specific capacity (1,382, 1,242 and 1,115 mA h g( 1) at 0.5, 1 and 2 C, respectively), long cycling life (small capacity decay of 0.039% per cycle over 1,000 cycles at 2 C) and excellent rate capability at a high charge/discharge current. PMID- 26830733 TI - A comparison of fresh, pasta filata, and aged Hispanic cheeses using sensory, chemical, functional, and microbiological assessments. AB - Anecdotal information suggests that some Hispanic consumers may consider US-made Hispanic cheeses as having a general lack of authenticity compared with those made in their countries of origin. To characterize the potential differences, samples of fresh, pasta filata, and aged Hispanic cheeses were acquired from both the United States (total n=39) and countries of origin (total n=30) purchased from Mexico, Central America (Costa Rica and El Salvador), and the Caribbean (Puerto Rico). The proximate composition, microbial counts, melt profile, and sensory characteristics were evaluated and compared in country-of-origin cheeses and the US-made counterparts. The presence of Listeria spp. was confirmed for 1 Mexican aged cheese sample and 6 cheese samples from Central America (3 fresh, 2 pasta filata, and 1 aged). The chemical composition, melt profile, and sensory characteristics of fresh and pasta filata US Hispanic cheeses were not significantly different from their Mexican counterparts. Likewise, the chemical composition and melt profile of US aged Hispanic cheeses was not significantly different from the aged Mexican cheeses, but sensory characteristics varied among all aged cheeses. These results demonstrate the similarities and differences among US fresh, pasta filata, and aged Hispanic cheeses relative to their counterparts made in the countries of origin. PMID- 26830734 TI - Management practices on organic and conventional dairy herds in Minnesota. AB - The objective of this study was to describe and compare husbandry practices on organic and conventional dairy farms of similar sizes in Minnesota. Organic (ORG, n=35), same-sized conventional (SC, n=15, <200 cows) and medium-sized conventional (MC, n=13, >=200 cows) dairy herds were visited in 2012, and farmers were interviewed once about their farm, herd demographics, and herd management practices concerning nutrition, housing, and reproductive programs. Organic farms had been established as long as conventional farms, and ORG producers had most commonly selected ORG farming because of a negative perception of pesticides for human health. The distribution of cattle breeds and ages differed across farm types. Organic farms had more crossbred cows and a greater number of older cows than conventional farms, who had mainly Holstein cattle. Organic farms did not dock tails, were more likely to use breeding bulls, and were less likely to conduct pregnancy diagnoses in cattle. All conventional farmers fed corn, corn silage, and hay, but no forage or feed supplement was fed by all ORG farms with the exception of pasture. Kelp was supplemented on most ORG farms but on none of the conventional farms. In summary, although there were differences across farm types regarding the use of pasture, feeds, and feed additives, breed and age distribution, reproductive management, and the use of tail docking, observations in other management areas showed large overlap across herd types. PMID- 26830735 TI - Short communication: Lactic acid bacteria from the honeybee inhibit the in vitro growth of mastitis pathogens. AB - Despite the increasing knowledge of prevention and control strategies, bovine mastitis remains one of the most challenging diseases in the dairy industry. This study investigated the antimicrobial activity of 13 species of lactic acid bacteria (LAB), previously isolated from the honey crop of the honeybee, on several mastitis pathogens. The viable LAB were first reintroduced into a sterilized heather honey matrix. More than 20 different bovine mastitis isolates were tested against the mixture of the 13 LAB species in the honey medium using a dual-culture overlay assay. The mastitis isolates were identified through bacteriological culturing, followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Additionally, the mastitis isolates were subjected to antimicrobial susceptibility testing through disk diffusion. Growth of all tested mastitis pathogens, including the ones displaying antimicrobial resistance to one or more antimicrobial compounds, were inhibited to some extent by the honey and LAB combination. The antibacterial effect of these LAB opens up new perspectives on alternative treatment and prevention of bovine mastitis. PMID- 26830736 TI - Interaction between bovine-associated coagulase-negative staphylococci species and strains and bovine mammary epithelial cells reflects differences in ecology and epidemiological behavior. AB - Bacteria adherence seems to be an essential first stage for the internalization of bacteria into the cytoplasm of the host cell, which is considered an important virulence strategy enabling bacteria to occupy a microenvironment separated from host defense mechanisms. Thus, this study aimed to explore the difference in the capacity of 4 bovine-associated staphylococci species or strains to adhere to and internalize into bovine mammary epithelial cells (MEC). Three different isolates of coagulase-negative staphylococci (CNS) were used: one strain of Staphylococcus fleurettii isolated from sawdust and considered an environmental opportunistic bacterium, and 2 dissimilar Staphylococcus chromogenes isolates, one cultured from a heifer's teat apex (Staph. chromogenes TA) and the other originating from a chronic intramammary infection (Staph. chromogenes IM). Also, one well characterized strain of Staphylococcus aureus (Newbould 305) was used for comparison with a major mastitis pathogen. The CNS species and strains adhered to and internalized into MEC slower than did Staph. aureus. Still, we observed high variation in adhesion and internalization capacity among the different CNS, with Staph. chromogenes IM showing a greater ability to adhere to and internalize into MEC than the 2 CNS strains isolated from extramammary habitats. In conclusion, the 3 well-characterized bovine-associated CNS species and strains originating from distinct habitats showed clear differences in their capacity to adhere to and internalize into MEC. The observed differences might be related to their diversity in ecology and epidemiological behavior. PMID- 26830737 TI - Characterizing individual differences in animal responses to a nutritional challenge: Toward improved robustness measures. AB - The aim of this paper was to explore the variation between individuals in the response to and recovery from a nutritional challenge, the repeatability of responses between lactation stages, and the use of shape-clustering methods to classify similar individuals. Sixteen dairy goats were exposed to a 2-d nutritional challenge (underfeeding) at 2 different stages of lactation. Each challenge consisted of a 7-d control period with standard total mixed ration (TMR), 2d of straw-only feeding, and a 10-d recovery period on the TMR. All feeds were offered ad libitum, as was water. The first challenge was in late lactation on primiparous goats (mean days in milk=249), and the second challenge was carried out on the same goats early in the following lactation (mean days in milk=28). The main energetic response traits dry matter intake (DMI), milk yield, body weight, milk fat and protein contents, and plasma glucose, fatty acids (NEFA), beta-hydroxybutyrate (BHB), urea, and insulin, were measured daily throughout. A clustering procedure linked to a piecewise mixed model was used to characterize different types of response. As expected, straw feeding caused a large decline in DMI and milk yield, and substantial increases in milk fat and milk protein composition, relative to the prechallenge period on the control TMR. For both DMI and milk yield, the slope of the response, and hence the size of the drop, was strongly related to the prechallenge values, indicating that these 2 measures were tightly constrained by the challenge. Regression slopes between lactation stages for responses to the same nutritional challenge were significant for DMI, milk protein content, plasma BHB and urea, and body weight, indicating that within-animal responses in late and early lactation were repeatable. The clustering procedure generally performed well, classifying both scaling differences and differences in shape. The extent of reranking of cluster designations between late lactation and the following early lactation period was examined. For milk yield, DMI, body weight, and urea, relatively little reranking occurred; the numbers of goats not changing class number were 10, 12, 10, and 13, respectively. In contrast, for milk contents of fat and protein, and also for BHB, no clear association was found between late and early lactation class numbers. For NEFA and glucose, these comparisons were not relevant because either the vast majority of goats were in 1 cluster (NEFA) or because an outlier goat skewed the cluster designation (glucose in late lactation). For insulin, 9 out of 16 goats kept the same rank. PMID- 26830738 TI - Invited review: Artisanal Mexican cheeses. AB - The objective of this review is to present an overview of some of the most commonly consumed artisanal Mexican cheeses, as well as those cheeses that show potential for a protected designation of origin. A description is given for each of these cheeses, including information on their distinguishing characteristics that makes some of them potential candidates for achieving a protected designation of origin status. This distinction could help to expand their frontiers and allow them to become better known and appreciated in other parts of the world. Due to the scarcity of scientific studies concerning artisanal Mexican cheeses, which would ultimately aid in the standardization of manufacturing processes and in the establishment of regulations related to their production, more than 40 varieties of artisanal cheese are in danger of disappearing. To preserve these cheeses, it is necessary to address this challenge by working jointly with government, artisanal cheesemaking organizations, industry, academics, and commercial partners on the implementation of strategies to protect and preserve their artisanal means of production. With sufficient information, official Mexican regulations could be established that would encompass and regulate the manufacture of Mexican artisanal cheeses. Finally, as many Mexican artisanal cheeses are produced from raw milk, more scientific studies are required to show the role of the lactic acid bacteria and their antagonistic effect on pathogenic microorganisms during aging following cheese making. PMID- 26830739 TI - Short communication: Serum composition of milk subjected to re-equilibration by dialysis at different temperatures, after pH adjustments. AB - The objective of this work was to investigate the properties of casein micelles after pH adjustment and their re-equilibration to the original pH and serum composition. Re-equilibration was carried out by dialyzing against skim milk at 2 different temperatures (4 or 22 degrees C). Turbidity, the average radius of the casein micelles, and the composition of the soluble phase were measured at different pH values, ranging between 5.5 and 8. Acidification led to the solubilization of colloidal calcium phosphate and decrease of the average radius of the micelles. With re-equilibration, casein dissociation occurred. In milk with pH values greater than 6.0, the average radius was recovered after re equilibration. At pH values greater than neutral, an increase of the radius of casein micelles and increased dissociation of the casein were found. After re equilibration, the radius of micelles and soluble protein in the serum decreased. The results were not affected by the temperature of re-equilibration. The changes to the calcium phosphate equilibrium and the dissociation of the micelles will have important consequences to the functionality of casein micelles. PMID- 26830740 TI - Nutritional strategies to optimize dairy cattle immunity. AB - Dairy cattle are susceptible to increased incidence and severity of both metabolic and infectious diseases during the periparturient period. A major contributing factor to increased health disorders is alterations in bovine immune mechanisms. Indeed, uncontrolled inflammation is a major contributing factor and a common link among several economically important infectious and metabolic diseases including mastitis, retained placenta, metritis, displaced abomasum, and ketosis. The nutritional status of dairy cows and the metabolism of specific nutrients are critical regulators of immune cell function. There is now a greater appreciation that certain mediators of the immune system can have a reciprocal effect on the metabolism of nutrients. Thus, any disturbances in nutritional or immunological homeostasis can provide deleterious feedback loops that can further enhance health disorders, increase production losses, and decrease the availability of safe and nutritious dairy foods for a growing global population. This review will discuss the complex interactions between nutrient metabolism and immune functions in periparturient dairy cattle. Details of how either deficiencies or overexposure to macro- and micronutrients can contribute to immune dysfunction and the subsequent development of health disorders will be presented. Specifically, the ways in which altered nutrient metabolism and oxidative stress can interact to compromise the immune system in transition cows will be discussed. A better understanding of the linkages between nutrition and immunity may facilitate the design of nutritional regimens that will reduce disease susceptibility in early lactation cows. PMID- 26830741 TI - Vacuum levels and milk-flow-dependent vacuum drops affect machine milking performance and teat condition in dairy cows. AB - Different levels of claw vacuum during machine milking may influence milking performance and teat condition. The claw vacuum acts on the teat and is responsible for removal and transport of milk but is also causing potential effects on the teat tissue. In the absence of milk flow, the claw vacuum is similar as the system vacuum. During milk flow, the claw vacuum drops to lower levels depending on lifting height and tube length and diameter, which may influence milking performance and the mechanical load on the teat tissue. The goal of the present study was to investigate the effects of high system vacuum and extremely low claw vacuum during milk flow on milking performance and teat condition after milking recorded by ultrasound. Treatments were control (treatment 1) with a system vacuum of 42 and a minimum claw vacuum during milk flow of 33 kPa; treatment 2 representing a system vacuum of 50 kPa, with a minimum claw vacuum almost similar as treatment 1 (34 kPa); and treatment 3 with the same system vacuum as treatment 1 but a claw vacuum drop during milk flow down to 24 kPa. Total milk yield was similar in all treatments, but strip yield was lower in treatment 3 than in the other treatments. Milk flow was similar in treatment 1 and treatment 2, but was reduced in treatment 3, thus causing a prolonged milking time in treatment 3. Teat wall thickness was increased and teat cistern diameter was decreased in treatment 2 as compared with the other treatments. The results demonstrate that the minimum claw vacuum had the main influence on milking performance independent of the level of the system vacuum and related vacuum drops and a low minimum claw vacuum caused low milk flow and long milking times. Teat condition at the end of milking, however, was mainly dependent on the system vacuum, and the load on the teat tissue was obviously increased at a system vacuum of 50 kPa. This effect was obviously occurring toward the end of milking when milk flow decreased and hence the milk flow dependent vacuum drop disappeared. Therefore, an early cluster detachment should be considered to avoid an increased effect on the teat tissue. Estimates of simulated early detachment levels in the present study of up to 1,000g/min lead to the assumption of minimal milk loss at simultaneously shorter machine-on time through the avoidance of lowest milk flow at the end of milking. PMID- 26830742 TI - Prediction of individual milk proteins including free amino acids in bovine milk using mid-infrared spectroscopy and their correlations with milk processing characteristics. AB - The aim of this study was to evaluate the effectiveness of mid-infrared spectroscopy in predicting milk protein and free amino acid (FAA) composition in bovine milk. Milk samples were collected from 7 Irish research herds and represented cows from a range of breeds, parities, and stages of lactation. Mid infrared spectral data in the range of 900 to 5,000 cm(-1) were available for 730 milk samples; gold standard methods were used to quantify individual protein fractions and FAA of these samples with a view to predicting these gold standard protein fractions and FAA levels with available mid-infrared spectroscopy data. Separate prediction equations were developed for each trait using partial least squares regression; accuracy of prediction was assessed using both cross validation on a calibration data set (n=400 to 591 samples) and external validation on an independent data set (n=143 to 294 samples). The accuracy of prediction in external validation was the same irrespective of whether undertaken on the entire external validation data set or just within the Holstein-Friesian breed. The strongest coefficient of correlation obtained for protein fractions in external validation was 0.74, 0.69, and 0.67 for total casein, total beta lactoglobulin, and beta-casein, respectively. Total proteins (i.e., total casein, total whey, and total lactoglobulin) were predicted with greater accuracy then their respective component traits; prediction accuracy using the infrared spectrum was superior to prediction using just milk protein concentration. Weak to moderate prediction accuracies were observed for FAA. The greatest coefficient of correlation in both cross validation and external validation was for Gly (0.75), indicating a moderate accuracy of prediction. Overall, the FAA prediction models overpredicted the gold standard values. Near-unity correlations existed between total casein and beta-casein irrespective of whether the traits were based on the gold standard (0.92) or mid-infrared spectroscopy predictions (0.95). Weaker correlations among FAA were observed than the correlations among the protein fractions. Pearson correlations between gold standard protein fractions and the milk processing characteristics of rennet coagulation time, curd firming time, curd firmness, heat coagulating time, pH, and casein micelle size were weak to moderate and ranged from -0.48 (protein and pH) to 0.50 (total casein and a30). Pearson correlations between gold standard FAA and these milk processing characteristics were also weak to moderate and ranged from -0.60 (Val and pH) to 0.49 (Val and K20). Results from this study indicate that mid-infrared spectroscopy has the potential to predict protein fractions and some FAA in milk at a population level. PMID- 26830743 TI - Antagonistics against pathogenic Bacillus cereus in milk fermentation by Lactobacillus plantarum ZDY2013 and its anti-adhesion effect on Caco-2 cells against pathogens. AB - Lactobacillus plantarum ZDY2013 is a potential probiotic isolated from fermented bean acid. In this study, we aimed to evaluate the in vitro antimicrobial activity of this organism against Bacillus cereus in milk fermentation, the antiadhesion ability on intestinal epithelial cells, as well as its ability to abrogate the cytotoxic effect and expression levels of genes. We found no antimicrobial activity produced by L. plantarum once the pH was adjusted to 6.0 and 7.0. The pH decreased continuously when L. plantarum and B. cereus were co incubated during milk fermentation, which caused a decrease in the B. cereus counts. Antiadhesion assays showed that L. plantarum can significantly inhibit the adhesion of enterotoxin-producing B. cereus ATCC14579 and pathogenic B. cereus HN001 by inhibition, competition, and displacement. The supernatants of B. cereus, either alone or in conjunction with L. plantarum, caused damage to the membrane integrity of Caco-2 cells to release lactate dehydrogenase. In addition, L. plantarum tended to attenuate proinflammatory cytokine and oxidative stress gene expression on Caco-2 cells, inducing with B. cereus HN001 supernatants. This study provided systematic insights into the antagonistic effect of L. plantarum ZDY2013, and the information may be helpful to explore potential control measures for preventing food poisoning by lactic acid bacteria. PMID- 26830744 TI - Effect of sand and rubber surface on the lying behavior of lame dairy cows in hospital pens. AB - Housing lame cows in designated hospital pens with a soft surface may lessen the pain the animals feel when lying and changing position. This study investigated the effect of the lying surface on the behavior of lame cows in hospital pens. Thirty-two lame dairy cows were kept in individual hospital pens, provided with either 30-cm deep-bedded sand or 24-mm rubber mats during 24 h in a crossover design. On each surface, the lying behavior of each cow was recorded during 18 h. On deep-bedded sand, cows lay down more and changed position more often than when housed on the rubber surface. Furthermore, a shorter duration of lying down and getting up movements and a shorter duration of lying intention movements were observed. These results suggest that lame dairy cows are more reluctant to change position on rubber compared with sand, and that sand is more comfortable to lie on. Thus, deep bedding such as sand may provide better lying comfort for lame cows than an unbedded rubber surface. PMID- 26830745 TI - Reproductive management strategies to improve the fertility of cows with a suboptimal response to resynchronization of ovulation. AB - The objective was to compare the reproductive performance of lactating Holstein cows managed with a strategy that included the Ovsynch protocol with exogenous progesterone (P4) supplementation or presynchronization with GnRH 7d before Ovsynch to treat cows without a corpus luteum (CL), a CL <15 mm, or cystic at the time of the PGF2alpha injection of Resynch (GnRH-7 d-PGF2alpha-56 h-GnRH-16 to 20 h-TAI). In a preliminary study, blood collection and transrectal ovarian ultrasonography were conducted (n=555) at the PGF2alpha of Resynch [coincident with nonpregnancy diagnosis (NPD)] to define a cutoff value for CL size that better predicted fertility after timed artificial insemination (TAI). A CL size of 15 mm was selected based on statistical differences in pregnancies per AI (P/AI) [33.2 vs. 10.3 P/AI for CL >=15 mm (n=497) vs. no CL >=15 mm (n=58; no CL, CL <15 mm, or cystic)]. Subsequently, in a completely randomized experiment, cows were enrolled in a management strategy that used Ovsynch with P4 supplementation [Ovsynch+P4; GnRH and controlled internal drug release device (CIDR)-7 d PGF2alpha and CIDR removal-56 h-GnRH-16 to 20 h-TAI] or a PreG-Ovsynch protocol [PreG-Ovsynch; GnRH-7 d-GnRH-7 d-PGF2alpha-56 h-GnRH-16 to 20 h-TAI] to treat cows without a CL, a CL <15 mm, or cystic at NPD and the PGF2alpha of Resynch. Cows with a CL >=15 mm at the PGF2alpha of Resynch completed the protocol and received TAI. Data were available from 212, 192, and 1,797 AI services after Ovsynch+P4, PreG-Ovsynch, and Resynch, respectively. At 39d after AI, P/AI tended to be greater for Ovsynch+P4 and PreG-Ovsynch combined (35.1%) than for Resynch cows (31.1%), whereas P/AI were similar for Ovsynch+P4 (34.4%) and PreG-Ovsynch (35.9%). The hazard of pregnancy for cows that received the experimental treatments at least once was similar for cows in the Ovsynch+P4 (n=124) and the PreG-Ovsynch (n=132) group (hazard ratio 1.15; 95% confidence interval: 0.87 to 1.53). Median days to pregnancy were 52 and 59 for cows in the Ovsynch+P4 and the PreG-Ovsynch groups, respectively. The presynchronizing GnRH injection of PreG Ovsynch induced ovulation in 86.0% of the cows. At the first GnRH of Ovsynch, the proportion of cows with a CL based on ultrasound (86.6 vs. 15.0%), P4 >1 ng/mL (82.8 vs. 31.8%), a follicle >= 10 mm (98.0 vs. 84.4%), and P4 concentrations (3.7 vs. 1.1 ng/mL) was greater in PreG-Ovsynch than in Ovsynch+P4. Conversely, more cows ovulated in response to the first GnRH of Ovsynch in Ovsynch+P4 (71.9%) than PreG-Ovsynch (58.3%). At the PGF2alpha before TAI, more cows had a CL based on ultrasound (92.1 vs. 77.0%) and P4 concentrations were greater in PreG-Ovsynch than in Ovsynch+P4 (4.1 vs. 2.6 ng/mL); however, a similar proportion of cows had P4 >1 ng/mL (79.1 vs. 82.7%). We conclude that the Ovsynch+P4 and PreG-Ovsynch treatments for cows without a CL, a CL <15 mm, or cystic at the PGF2alpha injection of Resynch led to P/AI similar to that of cows with a CL >=15 mm, and that both management strategies resulted in similar time to pregnancy. PMID- 26830746 TI - Detection and quantification of viable Bacillus cereus group species in milk by propidium monoazide quantitative real-time PCR. AB - The Bacillus cereus group includes important spore-forming bacteria that present spoilage capability and may cause foodborne diseases. These microorganisms are traditionally evaluated in food using culturing methods, which can be laborious and time-consuming, and may also fail to detect bacteria in a viable but nonculturable state. The purpose of this study was to develop a quantitative real time PCR (qPCR) combined with a propidium monoazide (PMA) treatment to analyze the contamination of UHT milk by B. cereus group species viable cells. Thirty micrograms per milliliter of PMA was shown to be the most effective concentration for reducing the PCR amplification of extracellular DNA and DNA from dead cells. The quantification limit of the PMA-qPCR assay was 7.5 * 10(2) cfu/mL of milk. One hundred thirty-five UHT milk samples were analyzed to evaluate the association of PMA to qPCR to selectively detect viable cells. The PMA-qPCR was able to detect B. cereus group species in 44 samples (32.6%), whereas qPCR without PMA detected 78 positive samples (57.8%). Therefore, the PMA probably inhibited the amplification of DNA from cells that were killed during UHT processing, which avoided an overestimation of bacterial cells when using qPCR and, thus, did not overvalue potential health risks. A culture-based method was also used to detect and quantify B. cereus sensu stricto in the same samples and showed positive results in 15 (11.1%) samples. The culture method and PMA-qPCR allowed the detection of B. cereus sensu stricto in quantities compatible with the infective dose required to cause foodborne disease in 3 samples, indicating that, depending on the storage conditions, even after UHT treatment, infective doses may be reached in ready-to-consume products. PMID- 26830747 TI - Identification and molecular phylogeny of coagulase-negative staphylococci isolates from Minas Frescal cheese in southeastern Brazil: Superantigenic toxin production and antibiotic resistance. AB - Minas Frescal is a typical Brazilian fresh cheese and one of the most popular dairy products in the country. This white soft, semiskimmed, nonripened cheese with high moisture content is obtained by enzymatic coagulation of cow milk using calf rennet or coagulants, usually in industrial dairy plants, but is also manufactured in small farms. Contamination of Minas Frescal by several staphylococci has been frequently reported. Coagulase-negative staphylococci (CNS) strains are maybe the most harmful, as they are able to produce heat-stable enterotoxins with super antigenic activities in food matrices, especially in dairy products such as soft cheeses. The aim of the present study was to investigate the presence of CNS strains in Minas Frescal marketed in southeastern Brazil concerning the risk of staphylococci food poisoning by the consumption of improperly manufactured cheese and the possibility of these food matrices being a reservoir of staphylococcal resistance to antimicrobials. Ten distinct CNS strains were found in 6 cheeses from distinct brands. The most frequent species were Staphylococcus saprophyticus (40%), Staphylococcus xylosus (30%), Staphylococcus sciuri (20%), and Staphylococcus piscifermentans (10%). Three strains were identified to the Staphylococcus genera. Three major species groups composed of 3 refined clusters were grouped by phylogenetic analyses with similarities over to 90%. All CNS strains carried multiple enterotoxin genes, with high incidence of sea and seb (90 and 70%, respectively), followed by sec/see, seh/sei, and sed with intermediate incidence (60, 50, and 40%, respectively), and, finally, seg/selk/selq/selr and selu with the lowest incidence (20 and 10%, respectively). Real-time reverse transcription PCR and ELISA assays confirmed the enteroxigenic character of the CNS strains, which expressed and produced the enterotoxins in vitro. The CNS strains showed multiresistance to antimicrobial agents such as beta-lactams, vancomycin, and linezolid, which have therapeutic importance in both human and veterinarian medicines. The risk of staphylococci food poisoning by the consumption of improperly manufactured Minas Frescal was emphasized, in addition to the possibility of these food matrices being a reservoir for antibiotic resistance. More effective control measures concerning the presence and typing of staphylococci in raw milk and dairy derivatives should be included to prevent the spread of pathogenic strains. PMID- 26830748 TI - Invited review: Carryover effects of early lactation feeding on total lactation performance in dairy cows. AB - In comparison with the intensive research on the direct effects of energy supply on dairy cow lactation performance, little attention has been paid to the effect of early lactation feeding on subsequent production. The present paper reviews 9 studies carried out with the aim of quantifying the immediate and subsequent responses in milk production and body weight to early lactation feeding. Most results showed that a more generous feeding in early lactation caused a positive carryover effect on subsequent production, whereas an inadequate level of feed in early lactation has been shown to reduce subsequent milk yield. The carryover periods ranged from 3 to 12 wk and the difference in milk yield between cows in the carryover periods ranged between 1.5 and 4.5kg of milk/cow per day. When calculated as a percentage of the immediate effect, the carryover effect ranged from 22 to 63%. In 2 of the 9 papers reviewed, the authors found no carryover effect, probably due to the long post-treatment periods in these studies. This is supported by the other studies in which the carryover effect was only significant in a limited period after end of treatment. The magnitude of the carryover effect seems to be determined by several factors including duration of the treatment and post-treatment feeding level. The most important factor though appears to be the magnitude of over- or underfeeding (i.e., a strong relationship between the treatment period feeding level and the subsequent response in production). PMID- 26830749 TI - Conjugated linoleic acids influence fatty acid metabolism in ovine ruminal epithelial cells. AB - Conjugated linoleic acids (CLA), particularly cis-9,trans-11 (c9t11) and trans 10,cis-12 (t10c12), are used as feed additives to adapt to constantly increasing demands on the performance of lactating cows. Under these feeding conditions, the rumen wall, and the rumen epithelial cells (REC) in particular, are directly exposed to high amounts of CLA. This study determined the effect of CLA on the fatty acid (FA) metabolism of REC and expression of genes known to be modulated by FA. Cultured REC were incubated with c9t11, t10c12, and the structurally similar FA linoleic acid (LA), oleic acid (OA), and trans-vaccenic acid (TVA) for 48 h at a concentration of 100 uM. Cellular FA levels were determined by gas chromatography. Messenger RNA expression levels of stearoyl-CoA desaturase (SCD) and monocarboxylate transporter (MCT) 1 and 4 were quantified by reverse transcription-quantitative PCR. Fatty acid evaluation revealed significant effects of CLA, LA, OA, and TVA on the amount of FA metabolites of beta-oxidation and elongation and of metabolites related to desaturation by SCD. The observed changes in FA content point (among others) to the ability of REC to synthesize c9t11 from TVA endogenously. The mRNA expression levels of SCD identified a decrease after CLA, LA, OA, or TVA treatment. In line with the changes in mRNA expression, we found reduced amounts of C16:1n-7 cis-9 and C18:1n-9 cis-9, the main products of SCD. The expression of MCT1 mRNA increased after c9t11 and t10c12 treatment, and CLA c9t11 induced an upregulation of MCT4. Application of peroxisome proliferator-activated receptor (PPAR) alpha antagonist suggested that activation of PPARalpha is involved in the changes of MCT1, MCT4, and SCD mRNA expression induced by c9t11. Participation of PPARgamma in the changes of MCT1 and SCD mRNA expression was shown by the application of the respective antagonist. The study demonstrates that exposure to CLA affects both FA metabolism and regulatory pathways within REC. PMID- 26830750 TI - Contribution to the production of lactulose-rich whey by in situ electro isomerization of lactose and effect on whey proteins after electro-activation as confirmed by matrix-assisted laser desorption/ionization time-of-flight-mass spectrometry and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. AB - Cheese-whey, a major co-product of the dairy industry, has recently been the subject of many technological applications. We studied the bioconversion of whey into valuable bio-products such as a potential lactulose prebiotic and compounds with antioxidant properties. This paper examines efficiency, safety, and economics of electro-activation as an eco-friendly technology for a maximum valorization of whey. Thus, a bottom-up approach was therefore addressed. The effect of 4 experimental parameters--low working temperatures (0, 10, and 25 degrees C), current intensities (400, 600, and 800 mA), volume conditions (100, 200, and 300 mL), and feed concentrations [7, 14, and 28% (wt/vol)]--on lactose whey isomerization to lactulose under electro-activation process were studied. Structural characteristics of whey proteins and antioxidant functionality were also investigated. The results showed a compromise to be reached between both parameters. Therefore, the maximum yield of 35% of lactulose was achieved after 40 min of reaction at the working temperature of 10 degrees C under 400 mA electric current field and 100-mL volume conditions with using feed solution at 7% (wt/vol). The isomerization of lactose to lactulose is accomplished by subsequent degradation to galactose, but only at a very small amount. Additionally, whey electro-activation showed significantly elevated antioxidant capacity compared with the untreated samples. The enhancement of antioxidant functionality of whey electro-activation resulted from the synergistic effect of its partial hydrolysis and the formation of antioxidant components that were able to scavenge free radicals. In conclusion, the findings of this study reveal that the whey treated by the safety electro-activation technology has both lactulose prebiotic and antioxidant properties and could have a substantial application in the manufacture of pharmaceutical and functional foods. PMID- 26830751 TI - Effect of short- and long-term heat stress on the conception risk of dairy cows under natural service and artificial insemination breeding programs. AB - The objectives of this retrospective study were to examine the effect of heat stress on natural service and artificial insemination (AI) breeding methods. We investigated the influence of short- and long-term heat stress on the conception risk (CR) of dairy cows bred by natural service or by AI with frozen-thawed or fresh semen. In addition, the relationship between breeding method and parity was determined. Cows bred by AI with frozen-thawed semen exposed to long-term heat stress (mean temperature-humidity index >=73 in the period 21d before breeding) were 63% less likely to get pregnant compared with cows not exposed to heat stress. Cows bred by AI with fresh semen were 80% less likely to get pregnant during periods of short-term heat stress than during periods without heat stress. Furthermore, multiparous cows bred by AI with frozen-thawed or fresh semen were 22 and 67% less likely to get pregnant, respectively, than primiparous cows. No influence of heat stress or parity was noted on the CR of cows bred by natural service. The present study indicates that the likelihood of dairy cows becoming pregnant is reduced by short- and long-term heat stress depending on the type of semen employed. In particular, CR of cows inseminated with fresh semen is negatively affected by short-term heat stress and CR of cows inseminated with frozen-thawed semen is negatively affected by long-term heat stress. PMID- 26830753 TI - Editor's perspectives - January 2016. PMID- 26830752 TI - Pancreatic cancer. AB - Pancreatic cancer is a highly lethal disease, for which mortality closely parallels incidence. Most patients with pancreatic cancer remain asymptomatic until the disease reaches an advanced stage. There is no standard programme for screening patients at high risk of pancreatic cancer (eg, those with a family history of pancreatic cancer and chronic pancreatitis). Most pancreatic cancers arise from microscopic non-invasive epithelial proliferations within the pancreatic ducts, referred to as pancreatic intraepithelial neoplasias. There are four major driver genes for pancreatic cancer: KRAS, CDKN2A, TP53, and SMAD4. KRAS mutation and alterations in CDKN2A are early events in pancreatic tumorigenesis. Endoscopic ultrasonography and endoscopic ultrasonography-guided fine-needle aspiration offer high diagnostic ability for pancreatic cancer. Surgical resection is regarded as the only potentially curative treatment, and adjuvant chemotherapy with gemcitabine or S-1, an oral fluoropyrimidine derivative, is given after surgery. FOLFIRINOX (fluorouracil, folinic acid [leucovorin], irinotecan, and oxaliplatin) and gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) are the treatments of choice for patients who are not surgical candidates but have good performance status. PMID- 26830754 TI - Supercurrent in van der Waals Josephson junction. AB - Supercurrent flow between two superconductors with different order parameters, a phenomenon known as the Josephson effect, can be achieved by inserting a non superconducting material between two superconductors to decouple their wavefunctions. These Josephson junctions have been employed in fields ranging from digital to quantum electronics, yet their functionality is limited by the interface quality and use of non-superconducting material. Here we show that by exfoliating a layered dichalcogenide (NbSe2) superconductor, the van der Waals (vdW) contact between the cleaved surfaces can instead be used to construct a Josephson junction. This is made possible by recent advances in vdW heterostructure technology, with an atomically flat vdW interface free of oxidation and inter-diffusion achieved by eliminating all heat treatment during junction preparation. Here we demonstrate that this artificially created vdW interface provides sufficient decoupling of the wavefunctions of the two NbSe2 crystals, with the vdW Josephson junction exhibiting a high supercurrent transparency. PMID- 26830755 TI - Global spatially explicit CO2 emission metrics for forest bioenergy. AB - Emission metrics aggregate climate impacts of greenhouse gases to common units such as CO2-equivalents (CO2-eq.). Examples include the global warming potential (GWP), the global temperature change potential (GTP) and the absolute sustained emission temperature (aSET). Despite the importance of biomass as a primary energy supplier in existing and future scenarios, emission metrics for CO2 from forest bioenergy are only available on a case-specific basis. Here, we produce global spatially explicit emission metrics for CO2 emissions from forest bioenergy and illustrate their applications to global emissions in 2015 and until 2100 under the RCP8.5 scenario. We obtain global average values of 0.49 +/- 0.03 kgCO2-eq. kgCO2(-1) (mean +/- standard deviation) for GWP, 0.05 +/- 0.05 kgCO2 eq. kgCO2(-1) for GTP, and 2.14.10(-14) +/- 0.11.10(-14) degrees C (kg yr(-1))( 1) for aSET. We explore metric dependencies on temperature, precipitation, biomass turnover times and extraction rates of forest residues. We find relatively high emission metrics with low precipitation, long rotation times and low residue extraction rates. Our results provide a basis for assessing CO2 emissions from forest bioenergy under different indicators and across various spatial and temporal scales. PMID- 26830756 TI - Soluble neprilysin retains catalytic activity in heart failure. PMID- 26830757 TI - Variations of characteristic time scales in rotating stratified turbulence using a large parametric numerical study. AB - We study rotating stratified turbulence (RST) making use of numerical data stemming from a large parametric study varying the Reynolds, Froude and Rossby numbers, Re, Fr and Ro in a broad range of values. The computations are performed using periodic boundary conditions on grids of 1024(3) points, with no modeling of the small scales, no forcing and with large-scale random initial conditions for the velocity field only, and there are altogether 65 runs analyzed in this paper. The buoyancy Reynolds number defined as R(B) = ReFr2 varies from negligible values to ~ 10(5), approaching atmospheric or oceanic regimes. This preliminary analysis deals with the variation of characteristic time scales of RST with dimensionless parameters, focusing on the role played by the partition of energy between the kinetic and potential modes, as a key ingredient for modeling the dynamics of such flows. We find that neither rotation nor the ratio of the Brunt-Vaisala frequency to the inertial frequency seem to play a major role in the absence of forcing in the global dynamics of the small-scale kinetic and potential modes. Specifically, in these computations, mostly in regimes of wave turbulence, characteristic times based on the ratio of energy to dissipation of the velocity and temperature fluctuations, T(V) and T(P), vary substantially with parameters. Their ratio gamma=T(V)/T(P) follows roughly a bell-shaped curve in terms of Richardson number Ri. It reaches a plateau - on which time scales become comparable, gamma~0.6 - when the turbulence has significantly strengthened, leading to numerous destabilization events together with a tendency towards an isotropization of the flow. PMID- 26830758 TI - Method to disperse lipids as aggregates in oil for bilayers production. AB - Several techniques to assemble artificial lipid bilayers involve the zipping of monolayers. Their efficiency is determined by the renewal of the saturated monolayers to be zipped and this proceeds by adsorption of lipids dispersed in oil as aggregates. The size of these lipids aggregates is a key parameter to ensure both the stability of the suspension and a fast release of lipids at the interface. We propose a new method inspired from the solvent-shifting nucleation process allowing to control and tune the lipid aggregates size and that improves the production of artificial membranes. It is simpler and faster than current methods starting from a dry lipid film, which are highly sensitive to environmental conditions. This method opens the route to bilayer production processes with new potentialities in membrane composition. PMID- 26830759 TI - Water jet indentation for local elasticity measurements of soft materials. AB - We present a novel elastography method for soft materials (100Pa-100kPa) based on indentation by a MUm-sized water jet. We show that the jet creates a localized deformation ("cavity") of the material that can be easily visualized. We study experimentally how cavity width and depth depend on jet speed, height, incidence angle and sample elasticity. We describe how to calibrate the indenter using gels of known stiffness. We then demonstrate that the indenter yields quantitative elasticity values within 10% of those measured by shear rheometry. We corroborate our experimental findings with fluid-solid finite-element simulations that quantitatively predict the cavity profile and fluid flow lines. The water jet indenter permits in situ local stiffness measurements of 2D or 3D gels used for cell culture in physiological buffer, is able to assess stiffness heterogeneities with a lateral resolution in the range 50-500MUm (at the tissue scale) and can be assembled at low cost with standard material from a biology laboratory. We therefore believe it will become a valuable method to measure the stiffness of a wide range of soft, synthetic or biological materials. PMID- 26830760 TI - Discrete-continuous reaction-diffusion model with mobile point-like sources and sinks. AB - In many applications in soft and biological physics, there are multiple time and length scales involved but often with a distinct separation between them. For instance, in enzyme kinetics, enzymes are relatively large, move slowly and their copy numbers are typically small, while the metabolites (being transformed by these enzymes) are often present in abundance, are small in size and diffuse fast. It seems thus natural to apply different techniques to different time and length levels and couple them. Here we explore this possibility by constructing a stochastic-deterministic discrete-continuous reaction-diffusion model with mobile sources and sinks. Such an approach allows in particular to separate different sources of stochasticity. We demonstrate its application by modelling enzyme catalysed reactions with freely diffusing enzymes and a heterogeneous source of metabolites. Our calculations suggest that using a higher amount of less active enzymes, as compared to fewer more active enzymes, reduces the metabolite pool size and correspondingly the lag time, giving rise to a faster response to external stimuli. The methodology presented can be extended to more complex systems and offers exciting possibilities for studying problems where spatial heterogeneities, stochasticity or discreteness play a role. PMID- 26830761 TI - Quantitative phospho-proteomics reveals the Plasmodium merozoite triggers pre invasion host kinase modification of the red cell cytoskeleton. AB - The invasive blood-stage malaria parasite - the merozoite - induces rapid morphological changes to the target erythrocyte during entry. However, evidence for active molecular changes in the host cell that accompany merozoite invasion is lacking. Here, we use invasion inhibition assays, erythrocyte resealing and high-definition imaging to explore red cell responses during invasion. We show that although merozoite entry does not involve erythrocyte actin reorganisation, it does require ATP to complete the process. Towards dissecting the ATP requirement, we present an in depth quantitative phospho-proteomic analysis of the erythrocyte during each stage of invasion. Specifically, we demonstrate extensive increased phosphorylation of erythrocyte proteins on merozoite attachment, including modification of the cytoskeletal proteins beta-spectrin and PIEZO1. The association with merozoite contact but not active entry demonstrates that parasite-dependent phosphorylation is mediated by host-cell kinase activity. This provides the first evidence that the erythrocyte is stimulated to respond to early invasion events through molecular changes in its membrane architecture. PMID- 26830762 TI - Detecting O2 binding sites in protein cavities. AB - Internal cavities are important elements in protein structure, dynamics, stability and function. Here we use NMR spectroscopy to investigate the binding of molecular oxygen (O2) to cavities in a well-studied model for ligand binding, the L99A mutant of T4 lysozyme. On increasing the O2 concentration to 8.9 mM, changes in (1)H, (15)N, and (13)C chemical shifts and signal broadening were observed specifically for backbone amide and side chain methyl groups located around the two hydrophobic cavities of the protein. O2-induced longitudinal relaxation enhancements for amide and methyl protons could be adequately accounted for by paramagnetic dipolar relaxation. These data provide the first experimental demonstration that O2 binds specifically to the hydrophobic, and not the hydrophilic cavities, in a protein. Molecular dynamics simulations visualized the rotational and translational motions of O2 in the cavities, as well as the binding and egress of O2, suggesting that the channel consisting of helices D, E, G, H, and J could be the potential gateway for ligand binding to the protein. Due to strong paramagnetic relaxation effects, O2 gas-pressure NMR measurements can detect hydrophobic cavities when populated to as little as 1%, and thereby provide a general and highly sensitive method for detecting oxygen binding in proteins. PMID- 26830763 TI - Voltage divider effect for the improvement of variability and endurance of TaO(x) memristor. AB - The impact of a series resistor (R(S)) on the variability and endurance performance of memristor was studied in the TaO(x) memristive system. A dynamic voltage divider between the R(S) and memristor during both the set and the reset switching cycles can suppress the inherent irregularity of the voltage dropped on the memristor, resulting in a greatly reduced switching variability. By selecting the proper resistance value of R(S) for the set and reset cycles respectively, we observed a dramatically improved endurance of the TaO(x) memristor. Such a voltage divider effect can thus be critical for the memristor applications that require low variability, high endurance and fast speed. PMID- 26830764 TI - Reversible cardiac hypertrophy induced by PEG-coated gold nanoparticles in mice. AB - Gold nanoparticles (GNPs) are attracting more and more attention for their great potential value in biomedical application. Currently, no study has been reported on the chronic cardiac toxicity of GNPs after repeated administration. Here we carried out a comprehensive evaluation of the chronic cardiac toxicity of GNPs to the heart. Polyethylene glycol (PEG) -coated GNPs at three different sizes (10, 30 and 50 nm) or PBS was administrated to mice via tail vein for 14 consecutive days. Then the mice were euthanized at 2 weeks, 4 weeks or 12 weeks after the first injection. The accumulation of GNPs in the mouse heart and their effects on cardiac function, structure, fibrosis and inflammation were analysized. GNPs with smaller size showed higher accumulation and faster elimination. None of the three sizes of GNPs affected cardiac systolic function. The LVIDd (left ventricular end diastolicinner-dimension), LVMass (left ventricular mass) and HW/BW (heart weight/body weight) were significantly increased in the mice receiving 10 nm PEG GNPs for 2 weeks, but not for 4 weeks or 12 weeks. These results indicated that the accumulation of small size GNPs can induce reversible cardiac hypertrophy. Our results provide the basis for the further biomedical applications of GNPs in cardiac diseases. PMID- 26830765 TI - SOXC Genes and the Control of Skeletogenesis. AB - The SOXC group of transcription factors, composed of SOX4, SOX11, and SOX12, has evolved to fulfill key functions in cell fate determination. Expressed in many types of progenitor/stem cells, including skeletal progenitors, SOXC proteins potentiate pathways critical for cell survival and differentiation. As skeletogenesis unfolds, SOXC proteins ensure cartilage primordia delineation by amplifying canonical WNT signaling and antagonizing the chondrogenic action of SOX9 in perichondrium and presumptive articular joint cells. They then ensure skeletal elongation by inducing growth plate formation via enabling non-canonical WNT signaling. Human studies have associated SOX4 with bone mineral density and fracture risk in osteoporotic patients, and SOX11 with Coffin-Siris, a syndrome that includes skeletal dysmorphism. Meanwhile, in vitro and mouse studies have suggested important cell-autonomous roles for SOXC proteins in osteoblastogenesis. We here review current knowledge and gaps in understanding of SOXC protein functions, with an emphasis on the skeleton and possible links to osteoporosis. PMID- 26830766 TI - Enhanced renoprotective effect of IGF-1 modified human umbilical cord-derived mesenchymal stem cells on gentamicin-induced acute kidney injury. AB - The therapeutic action of umbilical cord-derived mesenchymal stem cells (UC-MSCs) against acute kidney injury (AKI) has been demonstrated by several groups. However, how to further enhance the renoprotective effect of UC-MSCs and improve the therapy effect, are still unclear. In this study, we mainly investigated whether insulin-like growth factor-1 (IGF-1)-modified UC-MSCs hold an enhanced protective effect on gentamicin-induced AKI in vivo. Our results indicated that the IGF-1 overexpression could enhance the therapeutic action of human UC-MSCs, and the AKI rats treated with IGF-1-overexpressed UC-MSCs (UC-MSCs-IGF-1) showed better recovery of biochemical variables in serum or urine associated with renal function, histological injury and renal apoptosis, compared with AKI rats treated with normal UC-MSCs. RNA microarray analysis indicated that some key genes in the signal pathways associated with anti-oxidation, anti-inflammatory, and cell migratory capacity were up-regulated in UC-MSCs-IGF-1, and the results were further confirmed with qPCR. Furthermore, a series of detection in vitro and in vivo indicated that the UC-MSCs-IGF-1 hold better anti-oxidation, anti inflammatory, and cell migratory capacity for IGF-1 overexpression. Thus, our study indicated that enhancement of UC-MSCs bioactivities with IGF-1 overexpression could increase the UC-MSCs therapeutic potential and further developed a new therapeutic strategy for the treatment of AKI. PMID- 26830768 TI - Alternative Stimulation Intensities for Mapping Cortical Motor Area with Navigated TMS. AB - Navigated transcranial magnetic stimulation (nTMS) is becoming a popular tool in pre-operative mapping of functional motor areas. The stimulation intensities used in the mapping are commonly suprathreshold intensities with respect to the patient's resting motor threshold (rMT). There is no consensus on which suprathreshold intensity should be used nor on the optimal criteria for selecting the appropriate stimulation intensity (SI). In this study, the left motor cortices of 12 right-handed volunteers (8 males, age 24-61 years) were mapped using motor evoked potentials with an SI of 110 and 120 % of rMT and with an upper threshold (UT) estimated by the Mills-Nithi algorithm. The UT was significantly lower than 120 % of rMT (p < 0.001), while no significant difference was observed between UT and 110 % of rMT (p = 0.112). The representation sizes followed a similar trend, i.e. areas computed based on UT (5.9 cm(2)) and 110 % of rMT (5.0 cm(2)) being smaller than that of 120 % of rMT (8.8 cm(2)) (p <= 0.001). There was no difference in representation sizes between 110 % of rMT and UT. The variance in representation size was found to be significantly lower with UT compared to 120 % of rMT (p = 0.048, uncorrected), while there was no difference between 110 % of rMT and UT or 120 % of rMT. Indications of lowest inter-individual variation in representation size were observed with UT; this is possibly due to the fact that it takes into account the individual input-output characteristics of the motor cortex. Therefore, the UT seems to be a good option for SI in motor mapping applications to outline functional motor areas with nTMS and it could potentially reduce the inter individual variation caused by the selection of SI in motor mapping in pre surgical applications and radiosurgery planning. PMID- 26830767 TI - Detection and Magnetic Source Imaging of Fast Oscillations (40-160 Hz) Recorded with Magnetoencephalography in Focal Epilepsy Patients. AB - We present a framework to detect fast oscillations (FOs) in magnetoencephalography (MEG) and to perform magnetic source imaging (MSI) to determine the location and extent of their generators in the cortex. FOs can be of physiologic origin associated to sensory processing and memory consolidation. In epilepsy, FOs are of pathologic origin and biomarkers of the epileptogenic zone. Seventeen patients with focal epilepsy previously confirmed with identified FOs in scalp electroencephalography (EEG) were evaluated. To handle data deriving from large number of sensors (275 axial gradiometers) we used an automatic detector with high sensitivity. False positives were discarded by two human experts. MSI of the FOs was performed with the wavelet based maximum entropy on the mean method. We found FOs in 11/17 patients, in only one patient the channel with highest FO rate was not concordant with the epileptogenic region and might correspond to physiologic oscillations. MEG FOs rates were very low: 0.02-4.55 per minute. Compared to scalp EEG, detection sensitivity was lower, but the specificity higher in MEG. MSI of FOs showed concordance or partial concordance with proven generators of seizures and epileptiform activity in 10/11 patients. We have validated the proposed framework for the non-invasive study of FOs with MEG. The excellent overall concordance with other clinical gold standard evaluation tools indicates that MEG FOs can provide relevant information to guide implantation for intracranial EEG pre-surgical evaluation and for surgical treatment, and demonstrates the important added value of choosing appropriate FOs detection and source localization methods. PMID- 26830769 TI - Abnormal Functional Connectivity Density in Post-traumatic Stress Disorder. AB - Post-traumatic stress disorder (PTSD) is a psychiatric disorder that occurs in individuals who have experienced life-threatening mental traumas. Previous neuroimaging studies have indicated that the pathology of PTSD may be associated with the abnormal functional integration among brain regions. In the current study, we used functional connectivity density (FCD) mapping, a novel voxel-wise data-driven approach based on graph theory, to explore aberrant FC through the resting-state functional magnetic resonance imaging of the PTSD. We calculated both short- and long-range FCD in PTSD patients and healthy controls (HCs). Compared with HCs, PTSD patients showed significantly increased long-range FCD in the left dorsolateral prefrontal cortex (DLPFC), but no abnormal short-range FCD was found in PTSD. Furthermore, seed-based FC analysis of the left DLPFC showed increased connectivity in the left superior parietal lobe and visual cortex of PTSD patients. The results suggested that PTSD patients experienced a disruption of intrinsic long-range functional connections in the fronto-parietal network and visual cortex, which are associated with attention control and visual information processing. PMID- 26830770 TI - Reaction Time in a Visual 4-Choice Reaction Time Task: ERP Effects of Motor Preparation and Hemispheric Involvement. AB - Reaction time (RT), the most common measure of CNS efficiency, shows intra- and inter-individual variability. This may be accounted for by hemispheric specialization, individual neuroanatomy, and transient functional fluctuations between trials. To explore RT on these three levels, ERPs were measured in a visual 4-choice RT task with lateralized stimuli (left lateral, left middle, right middle, and right lateral) in 28 healthy right-handed subjects. We analyzed behavioral data, ERP microstates (MS), N1 and P3 components, and trial-by-trial variance. Across subjects, the N1 component was contralateral to the stimulation side. N1-MSs were stronger over the left hemisphere, and middle stimulation evoked stronger activation than lateral stimulation in both hemispheres. The P3 was larger for the right visual field stimulation. RTs were shorter for the right visual hemifield stimulation/right hand responses. Within subjects, covariance analysis of single trial ERPs with RTs showed consistent lateralized predictors of RT over the motor cortex (MC) in the 112-248 ms interval. Decreased RTs were related to negativity over the MC contralateral to the stimulation side, an effect that could be interpreted as the lateralized readiness potential (LRP), and which was strongest for right side stimulation. The covariance analysis linking individual mean RTs and individual mean ERPs showed a frontal negativity and an occipital positivity correlating with decreased RTs in the 212-232 ms interval. We concluded that a particular RT is a composite measure that depends on the appropriateness of the motor preparation to a particular response and on stimulus lateralization that selectively involves a particular hemisphere. PMID- 26830771 TI - Tailoring interventional arrhythmia therapy to individual patients: seeking the Art and the Science of Cardiac Electrophysiology in 2016. PMID- 26830773 TI - [Resuscitation: What's new, what's important, what's to be done?]. PMID- 26830772 TI - Natural genetic variation in Arabidopsis for responsiveness to plant growth promoting rhizobacteria. AB - The plant growth-promoting rhizobacterium (PGPR) Pseudomonas simiae WCS417r stimulates lateral root formation and increases shoot growth in Arabidopsis thaliana (Arabidopsis). These plant growth-stimulating effects are partly caused by volatile organic compounds (VOCs) produced by the bacterium. Here, we performed a genome-wide association (GWA) study on natural genetic variation in Arabidopsis for the ability to profit from rhizobacteria-mediated plant growth promotion. To this end, 302 Arabidopsis accessions were tested for root architecture characteristics and shoot fresh weight in response to exposure to WCS417r. Although virtually all Arabidopsis accessions tested responded positively to WCS417r, there was a large variation between accessions in the increase in shoot fresh weight, the extra number of lateral roots formed, and the effect on primary root length. Correlation analyses revealed that the bacterially mediated increase in shoot fresh weight is related to alterations in root architecture. GWA mapping for WCS417r-stimulated changes in root and shoot growth characteristics revealed 10 genetic loci highly associated with the responsiveness of Arabidopsis to the plant growth-promoting activity of WCS417r. Several of the underlying candidate genes have been implicated in important plant growth-related processes. These results demonstrate that plants possess natural genetic variation for the capacity to profit from the plant growth-promoting function of a beneficial rhizobacterium in their rhizosphere. This knowledge is a promising starting point for sustainable breeding strategies for future crops that are better able to maximize profitable functions from their root microbiome. PMID- 26830774 TI - [Worldwide experience with automated external defibrillators: What have we achieved? What else can we expect?]. AB - INTRODUCTION: In Germany approximately 70,000-100,000 SCD patients die from sudden cardiac death (SCD). SCD is not caused by a single factor but is a multifactorial problem. In 50 % of SCD victims, sudden cardiac death is the first manifestation of heart disease. SCD is caused by ventricular tachyarrhythmias in approximately 90 % of patients, whereas SCD is caused by bradyarrhythmias in 5-10 % of the patients. METHODS: Risk stratification is not possible in the majority of them prior to the fatal event. Early defibrillation is the method of choice to terminate ventricular fibrillation. Therefore, it is mandatory to install automatic external defibrillators (AED) in places with many people. There is general agreement that early defibrillation with automated external defibrillators (AED) is an effective tool to treat patients with ventricular fibrillation and will improve survival. CONCLUSION: It seems necessary to teach cardiocompression and AED use, also to children and adolescents. AED therapy "at home" did not improve survival in patients with cardiac arrest and can not be recommended. PMID- 26830775 TI - [Mismanagement in the arrhythmia recognition algorithm of the LifeVest(r) with consecutive fatal outcome]. AB - We describe for the first time the misinterpretation of a wearable cardioverter defibrillator in the arrhythmia recognition algorithm with subsequent fatal outcome of a multi-morbid patient with an ischemic cardiomyopathy and a highly reduced left ventricular pump function (30 %). The patient's death was preceded by a life-threatening shockable rhythm which was repeatedly documented, but ultimately not correctly recognized by the system and therefore not treated. PMID- 26830776 TI - [Transseptal puncture after device closure of patent foramen ovale: Is it feasible?]. AB - CASE REPORT: The case of a 40-year-old woman with paroxysmal symptomatic atrial fibrillation and implanted occluder of a patent foramen ovale (PFO; AMPLATZERTM Septal Occluder, St. Jude Medical) is reported. Due to the symptomic atrial fibrillation, pulmonary vein isolation was planned. METHODS: Under transesophageal, echocardiographic control the transseptal puncture was performed posterior inferior of the occluder without any complications. The pulmonary vein was successfully isolatedusing radiofrequency energy. CONCLUSION: This case demonstrates that transseptal puncture in pulmonary vein isolation with an inserted PFO occluder under additional transesophageal, echocardiographic monitoring is safe and feasible. PMID- 26830777 TI - Higher Insulin Resistance Level is Associated with Worse Clinical Response in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis. AB - Insulin resistance is linked to atherosclerotic cardiovascular diseases and stroke. We investigated whether there is a relationship between insulin resistance and clinical findings and outcomes of acute ischemic stroke patients treated with intravenous thrombolysis. In our study, 180 acute ischemic stroke non-diabetic patients treated with intravenous recombinant tissue-type plasminogen activator (iv rt-PA) were evaluated for insulin resistance assessed by homeostasis model assessment insulin resistance (HOMA-IR). The threshold for HOMA-IR was determined as 2.7. Patients were grouped as HOMA-IR > 2.7 and HOMA-IR <= 2.7. Clinical features at baseline, 24th hour, and 3rd month were examined. Computed tomography (CT) findings for hemorrhagic transformation were also assessed. Patients with HOMA-IR > 2.7 had significantly higher National Institutes of Health Stroke Scale (NIHSS) scores at 24th hour (p = 0.005) and higher modified Rankin Scale (mRS) scores at 3rd month (p = 0.011). Logistic regression analysis displayed that the presence of HOMA-IR > 2.7 increases the likelihood of poor outcome 2.93 times (confidence interval [CI] 1.001-1.079) (p = 0.003). There was no statistically significant difference between baseline clinical features, hemorrhagic transformation (p = 1.000), and mortality (p = 0.350) rates. Insulin resistance at higher levels seems to be associated with poor clinical courses and outcomes in patients who received iv rt-PA. PMID- 26830780 TI - [Efficacy, tolerability and safety of cannabinoids for chronic neuropathic pain: A systematic review of randomized controlled studies]. AB - BACKGROUND: Recently published systematic reviews came to different conclusions with respect to the efficacy, tolerability and safety of cannabinoids for treatment of chronic neuropathic pain. MATERIAL AND METHODS: A systematic search of the literature was carried out in MEDLINE, the Cochrane central register of controlled trials (CENTRAL) and clinicaltrials.gov up until November 2015. We included double-blind randomized placebo-controlled studies (RCT) of at least 2 weeks duration and with at least 9 patients per treatment arm comparing medicinal cannabis, plant-based or synthetic cannabinoids with placebo or any other active drug treatment in patients with chronic neuropathic pain. Clinical endpoints of the analyses were efficacy (more than 30 % or 50 % reduction of pain, average pain intensity, global improvement and health-related quality of life), tolerability (drop-out rate due to side effects, central nervous system and psychiatric side effects) and safety (severe side effects). Using a random effects model absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables. The methodological quality of RCTs was rated by the Cochrane risk of bias tool. RESULTS: We included 15 RCTs with 1619 participants. Study duration ranged between 2 and 15 weeks. Of the studies 10 used a plant-derived oromucosal spray with tetrahydrocannabinol/cannabidiol, 3 studies used a synthetic cannabinoid (2 with nabilone and 1 with dronabinol) and 2 studies used medicinal cannabis. The 13 studies with parallel or cross-over design yielded the following results with 95 % confidence intervals (CI): cannabinoids were superior to placebo in the reduction of mean pain intensity with SMD - 0.10 (95 % CI - 0.20- - 0.00, p = 0.05, 13 studies with 1565 participants), in the frequency of at least a 30 % reduction in pain with an RD of 0.10 [95 % CI 0.03-0.16, p = 0.004, 9 studies with 1346 participants, number needed to treat for additional benefit (NNTB) 14, 95 % CI 8-45] and in the frequency of a large or very large global improvement with an RD of 0.09 (95 % CI 0.01-0.17, p = 0.009, 7 studies with 1092 participants). There were no statistically significant differences between cannabinoids and placebo in the frequency of at least a 50 % reduction in pain, in improvement of health-related quality of life and in the frequency of serious adverse events. Patients treated with cannabinoids dropped out more frequently due to adverse events with an RD of 0.04 [95 % CI 0.01-0.07, p = 0.009, 11 studies with 1572 participants, number needed to treat for additional harm (NNTH) 19, 95 % CI 13-37], reported central nervous system side effects more frequently with an RD of 0.38 (95 % CI 0.18-0.58, p = 0.0003, 9 studies with 1304 participants, NNTH 3, 95 % CI 2-4) and psychiatric side effects with an RD of 0.11 (95 % CI 0.06-0.16, p < 0.0001, 9 studies with 1304 participants, NNTH 8, 95 % CI 7-12). CONCLUSION: Cannabinoids were marginally superior to placebo in terms of efficacy and inferior in terms of tolerability. Cannabinoids and placebo did not differ in terms of safety during the study period. Short-term and intermediate-term therapy with cannabinoids can be considered in selected patients with chronic neuropathic pain after failure of first-line and second line therapies. PMID- 26830781 TI - The pattern of a specimen of Pycnogonum litorale (Arthropoda, Pycnogonida) with a supernumerary leg can be explained with the "boundary model" of appendage formation. AB - A malformed adult female specimen of Pycnogonum litorale (Pycnogonida) with a supernumerary leg in the right body half is described concerning external and internal structures. The specimen was maintained in our laboratory culture after an injury in the right trunk region during a late postembryonic stage. The supernumerary leg is located between the second and third walking legs. The lateral processes connecting to these walking legs are fused to one large structure. Likewise, the coxae 1 of the second and third walking legs and of the supernumerary leg are fused to different degrees. The supernumerary leg is a complete walking leg with mirror image symmetry as evidenced by the position of joints and muscles. It is slightly smaller than the normal legs, but internally, it contains a branch of the ovary and a gut diverticulum as the other legs. The causes for this malformation pattern found in the Pycnogonum individual are reconstructed in the light of extirpation experiments in insects, which led to supernumerary mirror image legs, and the "boundary model" for appendage differentiation. PMID- 26830778 TI - The Importance of Considering Sex Differences in Translational Stroke Research. AB - Stroke is the second leading cause of death worldwide, and differences between men and women have been documented in incidence, prevalence, and outcome. Here, we reviewed the literature on sex differences in stroke severity, mortality, functional outcome, and response to therapies after ischemic stroke. Many of the sex differences in stroke severity and mortality are explained by differences in baseline demographics such as older age in women. However, women account for more stroke deaths, consistently suffer from worse stroke outcomes, and are more often institutionalized and permanently disabled than men. These sex differences in functional outcome are equalized after treatment with tissue plasminogen activator (tPA) and women may benefit more from treatment than men. However, this may depend on race, as African-American women have less of a response to tPA than other groups. Regarding endovascular treatments, the few existing studies that have investigated sex differences in stroke outcome point to equal benefit in both sexes; however, many clinical trials are relatively underpowered to detect sex differences. Further, we considered sex-specific effects in animal models of stroke and present recommendations for the performance of stroke studies in female animals. The male-biased use of research animals is distinguished from the clinical situation where there is a disproportionate and growing female stroke population. Stroke in women is greatly understudied, and including both sexes is especially important in both preclinical and clinical studies that evaluate potential stroke therapies. PMID- 26830782 TI - Revision total hip arthroplasty in the United States: national trends and in hospital outcomes. AB - PURPOSE: With the increasing number of primary total hip arthroplasties (THA) being performed, the frequency of revision surgery is also expected to increase. We analysed the immediate in-hospital complications and epidemiologic data of 3,469 revision and 18,186 primary THA cases. METHODS: The National Hospital Discharge Survey (NHDS) was evaluated between 2001 and 2010 for patients who underwent revision and primary THA. Patients were identified and included in our retrospective study based on ICD-9 procedure codes. RESULTS: The number of primary and revision THAs increased steadily from 2001 to 2010. The revision burden decreased for the same studied period (r = -0.92) to reach 13.9 % in 2010. The South region had higher revision burden of 17.4 % (p < 0.001). The primary THA group was more likely to be obese, morbidly obese, and have hypertension (p < 0.001). The revision THA group had an increased rate of blood transfusions (p < 0.001), deep venous thrombosis (p = 0.008), post-operative sepsis (p < 0.001), and wound complications (p < 0.001). The in-hospital mortality rate was also higher for the revision THA group (0.6 % versus 0.2 %, p < 0.001). CONCLUSIONS: The revision burden has undergone a steady decrease over the ten years studied and the reason for this is likely multifactorial. The South region had a significantly higher revision burden when compared to the rest of the United States. Larger hospitals tend to perform relatively more revisions. Revision THA patients are associated with longer hospital stay, higher complications rate, and higher in-hospital mortality rate. PMID- 26830784 TI - Fullerene-like MoSe2 nanoparticles-embedded CNT balls with excellent structural stability for highly reversible sodium-ion storage. AB - Three-dimensional (3D) porous-structured carbon nanotube (CNT) balls embedded with fullerene-like MoSe2 nanocrystals were successfully prepared by the spray pyrolysis process and subsequent selenization process. The MoO2-CNT composite balls prepared by spray pyrolysis transformed into the fullerene-like MoSe2/CNT (F-MoSe2/CNT) composite balls by the selenization process. The F-MoSe2/CNT composite balls exhibited superior sodium-ion storage properties to bare MoSe2 and MoSe2/CNT with a filled structure (N-MoSe2/CNT), both of which were prepared as comparison samples. The 250(th) discharge capacities of bare MoSe2, N MoSe2/CNT composite balls, and F-MoSe2/CNT composite balls were 144, 200, and 296 mA h g(-1), respectively, at a high current density of 1.0 A g(-1), and their capacity retentions measured from the second cycle were 37%, 66%, and 83%, respectively. The 10(th) discharge capacities of the F-MoSe2/CNT composite balls were 382, 346, 310, 280, and 255 mA h g(-1) at current densities of 0.2, 0.5, 1.5, 3.0, and 5.0 A g(-1), respectively. The synergetic effect of the fullerene like MoSe2 nanocrystals with ultrafine sizes and the CNT balls with a tangled and 3D porous structure and high electrical conductivity resulted in excellent sodium ion storage properties of the F-MoSe2/CNT composite balls. PMID- 26830783 TI - Comparing the early efficacies of autologous bone grafting and interbody fusion cages for treating degenerative lumbar instability in patients of different ages. AB - PURPOSE: The aim of this study was to compare the early efficacies of interbody fusion using autologous bone graft or an interbody fusion cage in a modified transforaminal lumbar interbody fusion (TLIF) in patients of different ages with degenerative lumbar instability. METHODS: Data from 33 patients with double segment degenerative lumbar instability treated with a modified TLIF combined with a posterior fixation system from December 2008 to June 2014 were retrospectively analyzed. The two segments separately received an interbody bone graft fusion and an interbody fusion cage. Patients were divided by age into group A (middle-aged and elderly group, age >= 55 years, n = 13) and group B (young adult group, age < 55 years, n = 20). The clinical efficacy of the modified TLIF combined with a posterior fixation system was assessed using the Japanese Orthopaedic Association (JOA), Oswestry Disability Index (ODI), and Visual Analogue Scale (VAS) scores obtained before and after surgery, and at final follow-up. We measured the mean intervertebral space height, intervertebral foramen height, lumbar lordosis angle, and inter-technique differences in the mean intervertebral space height and intervertebral foramen height. Interbody fusion was evaluated using the Suk standard. RESULTS: Patients in group A followed-up for 19.15 +/- 8.01 months. Patients in group B followed-up for 14.80 +/- 5.47 months. The post-operative JOA, ODI, VAS, and lumbar lordosis angle were improved significantly. Moreover, the early clinical follow-up effect was good. In group A, significant differences in the intervertebral foramen height post surgery and at final follow-up, and the mean intervertebral space height at final follow-up were noted. The intervertebral foramen and space heights were increased in the interbody cage group. In group B, a significant difference in the intervertebral foramen height at final follow-up was noted. The mean intervertebral space height post-surgery and at final follow-up was significantly increased between the two fusion methods. Bony fusion was achieved in all cases. The fusion time of autologous bone graft and interbody fusion cage was 5.46 +/- 1.20 months and 6.77 +/- 1.01 months respectively in group A, and 5.50 +/- 1.28 months and 6.35 +/- 1.76 months respectively in group B, the difference in fusion time between techniques was significant. CONCLUSION: At different ages, the interbody fusion cages can better preserve the intervertebral space and the intervertebral foramen height. However, autologous bone graft can rapidly achieve a bony fusion. Interbody fusion cages are therefore ideal for young adults, while autologous bone grafting is ideal for middle-aged and elderly patients who receive a modified TLIF. PMID- 26830785 TI - Fever of unknown origin (FUO) in a renal transplant recipient due to drug fever from sirolimus. AB - INTRODUCTION: A variety of medications may cause drug fever. Drug fevers may persist for days to weeks until diagnosis is considered. The diagnosis of drug fever is confirmed when there is resolution of fever within 3 days after the medication is discontinued. Only rarely do undiagnosed drug fevers persist for over 3 weeks to meet fever of unknown origin (FUO) criteria. FUOs due to drug fever are uncommon, and drug fevers due to immunosuppressive drugs are very rare. CASE REPORT: This is a case of a 58-year-old female renal transplant recipient who presented with FUO that remained undiagnosed for over 8 weeks. DISCUSSION: We believe this is the first reported case of an FUO due to drug fever from sirolimus in a renal transplant recipient. PMID- 26830786 TI - The rationale for third trimester testing of vertical HIV transmission in neonates with CMV infection. AB - We report on a late-preterm neonate with severe congenital cytomegalovirus (CMV) infection, refractory to antiviral therapy with ganciclovir. Subsequent immune diagnostics led to the finding of HIV infection at day 69, even though the mother tested negative for HIV in early pregnancy. Thus, in congenital CMV infection, HIV testing should be performed to elucidate maternal HIV seroconversion during late pregnancy. Our case strongly supports third trimester screening of HIV infection acquired during pregnancy, yet recommended only for women with traditional risk factors for HIV or living in an area of high HIV prevalence. PMID- 26830787 TI - How Well Does LCA Model Land Use Impacts on Biodiversity?--A Comparison with Approaches from Ecology and Conservation. AB - The modeling of land use impacts on biodiversity is considered a priority in life cycle assessment (LCA). Many diverging approaches have been proposed in an expanding literature on the topic. The UNEP/SETAC Life Cycle Initiative is engaged in building consensus on a shared modeling framework to highlight best practice and guide model application by practitioners. In this paper, we evaluated the performance of 31 models from both the LCA and the ecology/conservation literature (20 from LCA, 11 from non-LCA fields) according to a set of criteria reflecting (i) model completeness, (ii) biodiversity representation, (iii) impact pathway coverage, (iv) scientific quality, and (v) stakeholder acceptance. We show that LCA models tend to perform worse than those from ecology and conservation (although not significantly), implying room for improvement. We identify seven best-practice recommendations that can be implemented immediately to improve LCA models based on existing approaches in the literature. We further propose building a "consensus model" through weighted averaging of existing information, to complement future development. While our research focuses on conceptual model design, further quantitative comparison of promising models in shared case studies is an essential prerequisite for future informed model choice. PMID- 26830788 TI - A calixpyridinium-based supramolecular tandem assay for alkaline phosphatase and its application to ATP hydrolysis reaction. AB - We have successfully implemented the supramolecular tandem assay principle for the real-time, continuous, direct, and label-free monitoring of alkaline phosphatase activity through a fluorescence "switch-off" assay based on a novel calixpyridinium/dye reporter pair. Because several diseases can be preliminarily diagnosed in light of an abnormal level of alkaline phosphatase in serum, the application of tandem assays to selectively monitor alkaline phosphatase activity has feasible implications in disease diagnosis. PMID- 26830789 TI - Added value of lung window in detecting drug mules on non-contrast abdominal computed tomography. AB - We evaluated the added value of lung window in non-contrast computed tomography (CT) of suspected body packers or stuffers. Forty suspected drug mules who were referred to our tertiary toxicology center were included. The final diagnosis of drug mule was based on the detection of packs in stool examination or surgery. Non-contrast CT scans were retrospectively interpreted by two blinded radiologists in consensus before and after reviewing the lung window images. The diagnostic performance of abdominal window scans alone and scans in both abdominal and lung windows were subsequently compared. Seven body packers and 21 body stuffers were identified. The sensitivity, negative predictive value (NPV), and diagnostic accuracy of scans in detection of drug mules (either drug packers or stuffers) raised from 60.7, 52.1, and 72.5 to 64.2, 54.5, and 75.0 %, respectively, with a more number of packs being detected (114 vs. 105 packs). In the body packers group, the diagnostic performance of both abdominal windows scans and combined abdominal and lung windows scans were 100 %. In the body stuffers group, the sensitivity, NPV, and diagnostic accuracy of scans increased from 47.6, 52.1, and 55.0 to 52.3, 54.5, and 57.5 %, respectively, after the addition of lung windows. Reviewing the lung window on non-contrast abdominal CT can be helpful in detection of drug mules. PMID- 26830790 TI - ERCP in potentially resectable malignant biliary obstruction is frequently unsuccessful when performed outside of a comprehensive pancreaticobiliary center. AB - BACKGROUND AND OBJECTIVES: ERCP prior to pancreaticoduodenectomy is unnecessary in select patients. When performed, it should be in conjunction with endoscopic ultrasound (EUS) to increase diagnostic sensitivity and allow for metal stent placement. The aim of this study was to determine differences in endoscopic practice patterns at community medical centers (CMC) and a comprehensive pancreaticobiliary referral center (PBRC). METHODS: Retrospective cohort study of all patients seen at a PBRC for endoscopic and/or surgical management of potentially resectable malignant distal biliary obstruction from 1/2011 to 6/2014. RESULTS: Of 75 patients, 30 underwent endoscopic management at a CMC and 45 were initially managed at our PBRC. ERCP was attempted in 92% of patients. EUS was performed more frequently (100% vs. 13.3 %, P < 0.0001), ERCP was more successful (93% vs. 69%, P = 0.02), and metal stent placement more likely (41% vs. 5%, P = 0.005) at our PBRC compared to a CMC. The majority (81%) of patients undergoing initial endoscopy at a CMC required repeat endoscopy at our PBRC. CONCLUSIONS: Patients who are candidates for pancreaticoduodenectomy frequently undergo ERCP. At a CMC, ERCP is often unsuccessful, is rarely accompanied by EUS, and often requires repeat endoscopy. Our findings support regionalizing the management of suspected pancreatic malignancy into dedicated specialty centers. J. Surg. Oncol. 2016;113:647-651. (c) 2016 Wiley Periodicals, Inc. PMID- 26830791 TI - Polarization in RMnO3 multiferroics. AB - Some comments on the review by Sim et al. [(2016). Acta Cryst. B72, 3-19] are given. The review is devoted to hexagonal multiferroics RMnO3, in which there are ferroelectric and magnetic orders. Strong interaction between these orders causes a series of interesting properties of multiferroics. PMID- 26830792 TI - Hexagonal RMnO3: a model system for two-dimensional triangular lattice antiferromagnets. AB - The hexagonal RMnO3(h-RMnO3) are multiferroic materials, which exhibit the coexistence of a magnetic order and ferroelectricity. Their distinction is in their geometry that both results in an unusual mechanism to break inversion symmetry and also produces a two-dimensional triangular lattice of Mn spins, which is subject to geometrical magnetic frustration due to the antiferromagnetic interactions between nearest-neighbor Mn ions. This unique combination makes the h-RMnO3 a model system to test ideas of spin-lattice coupling, particularly when both the improper ferroelectricity and the Mn trimerization that appears to determine the symmetry of the magnetic structure arise from the same structure distortion. In this review we demonstrate how the use of both neutron and X-ray diffraction and inelastic neutron scattering techniques have been essential to paint this comprehensive and coherent picture of h-RMnO3. PMID- 26830793 TI - Salt screening and characterization of ciprofloxacin. AB - With the aim of improving the solubility of ciprofloxacin, polybasic organic acids were utilized to react with ciprofloxacin in different stoichiometric proportions. The use of the solvent drop grinding (SDG) method, as well as the solvent evaporation method, resulted in the crystalline salts ciprofloxacin/fumaric acid (1:1, 2:1), ciprofloxacin/maleic acid (1:1) and ciprofloxacin/citric acid (2:1). The solubilities of these salts in pure water (pH 7.0) were determined using high-performance liquid chromatography (HPLC) at 310 K, with the salts showing considerably greater solubility than ciprofloxacin itself and, interestingly, ciprofloxacin/fumaric acid (2:1) being more soluble than ciprofloxacin/fumaric acid (1:1). Intrigued by this phenomenon, we undertook a comparison of the crystal structures of the salts: the three-dimensional sandwich-like structure observed in the 2:1 salt indicates that the preferred stacking may be a factor in increasing the solubility of ciprofloxacin. PMID- 26830794 TI - Determining europium compositional fluctuations in partially stabilized zirconia nanopowders: a non-line-broadening-based method. AB - A method is reported for assessing the compositional fluctuations in a ceramic sample, based only on the determination of the crystalline lattice parameters. Pure tetragonal phase partially stabilized zirconia powders are synthesized through the co-precipitation method by incorporating 4% Eu(3+). The powder is subjected to compression cycles to promote the tetragonal-to-monoclinic transformation. The Rietveld analysis of the X-ray powder diffraction patterns, recorded after each compression cycle, gives information about the lattice parameters and monoclinic phase content. The determination of europium content in the residual tetragonal phase is accomplished considering the unit cell volume of t-ZrO2 using Vegard's law. Using this information the compositional fluctuations over the sample were determined by considering two possible distributions of lanthanide ion content in the powders: a Gaussian and a Log-normal one. It was found that the Gaussian distribution better fits the experimental data. It was eventually demonstrated that these results are physically meaningful. PMID- 26830795 TI - Electron density, disorder and polymorphism: high-resolution diffraction studies of the highly polymorphic neuralgic drug carbamazepine. AB - Analysis of neutron and high-resolution X-ray diffraction data on form (III) of carbamazepine at 100 K using the atoms in molecules (AIM) topological approach afforded excellent agreement between the experimental results and theoretical densities from the optimized gas-phase structure and from multipole modelling of static theoretical structure factors. The charge density analysis provides experimental confirmation of the partially localized pi-bonding suggested by the conventional structural formula, but the evidence for any significant C-N pi bonding is not strong. Hirshfeld atom refinement (HAR) gives H atom positional and anisotropic displacement parameters that agree very well with the neutron parameters. X-ray and neutron diffraction data on the dihydrate of carbemazepine strongly indicate a disordered orthorhombic crystal structure in the space group Cmca, rather than a monoclinic crystal structure in space group P2(1)/c. This disorder in the dihydrate structure has implications for both experimental and theoretical studies of polymorphism. PMID- 26830796 TI - Charge distribution as a tool to investigate structural details. IV. A new route to heteroligand polyhedra. AB - A new route to apply the charge distribution (CHARDI) method to structures based on heteroligand coordination polyhedra is presented. The previous algorithm used scale factors computed in an iterative way based on the assumption (which turned out to be not always correct) that a real over-under bonding effect affects mainly the anionic charges of each single anion, without grossly modifying the total charge of each type of anion. The new, more general approach is not based on any a priori assumption but treats separately the homoligand sub-polyhedra and attributes to each type of atom a fraction of the charge of the atom coordinated to it, computed in a self-consistent iterative way. The distinction between the bonding and non-bonding contact is also redefined in terms of the mean fictive ionic radii (MEFIR), without the need of an empirical parameter, used in the previous algorithm. CHARDI equations are generalized in terms of the new approach and a series of examples is presented. PMID- 26830797 TI - Identifying the multiplicity of crystallographically equivalent variants generated by iterative phase transformations in Ti. AB - This work describes phase transformations in Ti from a purely crystallographic perspective. Iterative heating and cooling above and below 1155 K induce phase transitions between a low-temperature h.c.p. (hexagonal close packed) (6/m mm) and a high-temperature b.c.c. (body centred cubic) (m3m) structure. The crystallography of the two phases has been found to be related by the Burgers Orientation Relationship (Burgers OR). The transitions are accompanied by changes in texture, as an ever-increasing number of crystallographically equivalent variants occur with every cycle. Identifying their multiplicity is important to relate the textures before and after the transformation, in order to predict the resultant one and refine its microstructure. The four-dimensional Frank space was utilized to describe both h.c.p. and b.c.c. structures within the same orthogonal framework, and thus allow for their easy numerical manipulation through matrix algebra. Crystallographic group decomposition showed that the common symmetry maintained in both groups was that of group 2/m; therefore, the symmetry operations that generated the variants were of groups 3m and 23 for cubic and hexagonal generations, respectively. The number of all potential variants was determined for the first three variant generations, and degeneracy was indeed detected, reducing the number of variants from 72 to 57 and from 432 to 180 for the second and third generations, respectively. Degeneracy was attributed on some special alignments of symmetry operators, as a result of the Burgers OR connecting the relative orientation of the two structures. PMID- 26830798 TI - Experimental and theoretical charge-density analysis of 1,4-bis(5-hexyl-2 thienyl)butane-1,4-dione: applications of a virtual-atom model. AB - The experimental and theoretical charge densities of 1,4-bis(5-hexyl-2 thienyl)butane-1,4-dione, a precursor in the synthesis of thiophene-based semiconductors and organic solar cells, are presented. A dummy bond charges spherical atom model is applied besides the multipolar atom model. The results show that the dummy bond charges model is accurate enough to calculate electrostatic-derived properties which are comparable with those obtained by the multipolar atom model. The refinement statistics and the residual electron density values are found to be intermediate between the independent atom and the multipolar formalisms. PMID- 26830799 TI - Crystal engineering: co-crystals of cinnamic acid derivatives with a pyridyl derivative co-crystallizer. AB - A number of hydrogen-bonded co-crystals, consisting of a cinnamic acid derivative and a pyridyl co-crystallizer, have been synthesized and their properties investigated by X-ray diffraction. Samples were prepared by recrystallization or solvent drop grinding of trans-cinnamic acid (1), 4-methylcinnamic acid (2), 4 methoxy cinnamic acid (3) or 3,4-methoxy cinnamic acid (4), with 4,4-dipyridyl (A), iso-nicotinamide (B) or nicotinamide (C). The X-ray single-crystal structures of seven novel co-crystals, obtained through recrystallization, are examined and the hydrogen-bonding interactions discussed. Consistent hydrogen bonding motifs were observed for samples prepared when using 4,4-dipyridyl (A) or iso-nicotinamide (B) as the co-crystallizing agent. Powder X-ray diffraction analysis of the samples prepared by solvent drop grinding suggests the formation of ten co-crystals. PMID- 26830800 TI - Crystal structure of monoclinic calcium pyrophosphate dihydrate (m-CPPD) involved in inflammatory reactions and osteoarthritis. AB - Pure monoclinic calcium pyrophosphate dihydrate (m-CPPD) has been synthesized and characterized by synchrotron powder X-ray diffraction and neutron diffraction. Rietveld refinement of complementary diffraction data has, for the first time, allowed the crystal structure of m-CPPD to be solved. The monoclinic system P2(1)/n was confirmed and unit-cell parameters determined: a = 12.60842 (4), b = 9.24278 (4), c = 6.74885 (2) A and beta = 104.9916 (3) degrees . Neutron diffraction data especially have allowed the precise determination of the position of H atoms in the structure. The relationship between the m-CPPD crystal structure and that of the triclinic calcium pyrophosphate dihydrate (t-CPPD) phase as well as other pyrophosphate phases involving other divalent cations are discussed by considering the inflammatory potential of these phases and/or their involvement in different diseases. These original structural data represent a key step in the understanding of the mechanisms of crystal formation involved in different types of arthritis and to improve early detection of calcium pyrophosphate (CPP) phases in vivo. PMID- 26830801 TI - A double stranded metal-organic assembly accommodating a pair of water trimers in the host cavity and catalysing Glaser coupling. AB - A supramolecular compound, catena-poly{[Cu2(1,3-MU2-(1a))2(MU2 ter)2(H2O)2]n.(6H2O)n} (1) has been synthesized using (1a) [(1a = N(1),N(3),N(5) trimethyl-N(1),N(3),N(5)-tris((pyridin-4-yl)methyl)-1,3,5-benzene tricarboxamide] and terephthalate (ter) as the pillaring unit by self-assembly. The terephthalate units are connected by copper(II) ions forming a single strand, while a pair of such strands are then linked by (1a) via two pyridyl terminal arms bound to copper(II) nodes on either side forming a one-dimensional double stranded assembly propagating along the c axis. The compound crystallizes in the Fdd2 space group. The cavity created in the interior of this double strand assembly trap six water molecules and are stabilized by hydrogen bonding with the host. The arrangement of the pair of acyclic water trimers in isolated cavities of (1) is such that it resembles a closed-bracket-like formation. The Hirshfeld surface analysis of (1) reveals the presence of strong intermolecular hydrogen-bonding interactions between one-dimensional ladder-like units and with the water trimer in the host cavity. The copper(II)-containing coordination polymer also acts as an efficient catalyst for the Glaser-Hay homo-coupling reaction. PMID- 26830802 TI - (3+1)-Incommensurately modulated crystal structure of Cs3ScSi6O15. AB - Single-crystal X-ray diffraction of Cs3ScSi6O15 shows the presence of main reflections and satellite reflections up to the fourth order along the c* direction. The (3+1)-dimensional incommensurately modulated structure was solved in superspace group X3m1(00gamma)0s0 [a = 13.861 (1), c = 6.992 (1) A, V = 1163.4 (2) A(3)] with a modulation wavevector q = 0.14153 (2)c*. Refinement of three modulation waves for positional and anisotropic displacement parameter values for all atoms converged to R(obs) values for all, main and satellite reflections of first, second and third order of 0.0200, 0.0166, 0.0181, 0.0214 and 0.0303, respectively. Cs3ScSi6O15 forms a mixed tetrahedral-octahedral framework with prominent six-membered rings of [SiO4]-tetrahedra interconnected by [ScO6] octahedra. Apart from Sc, all atoms are strongly affected by positional modulation with maximum atomic displacements of up to 0.93 A causing rigid polyhedral arrangements to perform tilt and twist movements relative to each other, such as a rotation of the Sc-octahedra around the 3-axis by over 38 degrees . Cs has an irregular coordination environment; however, considering distances up to 3.5 A, the bond-valence sum changes by no more than 0.02 as a function of t and thus overall kept at a level of ca 1.075. PMID- 26830803 TI - Reversible chair <-> skew conformational interconversion of 1,3,2 dioxaphosphorinane ring in the solid state. AB - beta-NH4[(MeO)2cDHAP] (where cDHAP is cyclic dihydroxyacetone phosphate) has been investigated by X-ray crystallography in the temperature range 350-100 K. Three reversible single-crystal-to-single-crystal phase transitions have been examined and four phases (high-, room-, medium- and low-temperature phase, HTP, RTP, MTP and LTP, respectively) have been structurally determined: HTP (at 350 K, P2(1)/a, Z = 24), RTP (290 K, P1, Z = 12), MTP (205 K, P2(1)/a, Z = 4) and LTP (100 K, P1, Z = 24). Various puckering modes of the 1,3,2-dioxaphosphorinane ring of the organic cyclic phosphate anion have been revealed in the crystal: chair and skew. The chair <-> skew ring flipping, which has been shown to take place during the phase transitions, results in various populations of skew and chair conformers in different phases. The flexibility in the coordination geometry of ammonium cations is considered to assist in the conformational flexibility of the dioxaphosphorinane ring. PMID- 26830804 TI - The low-temperature crystal structure of the multiferroic melilite Ca2CoSi2O7. AB - In the antiferromagnetic ground state, below TN ? 5.7 K, Ca2CoSi2O7 exhibits strong magnetoelectric coupling. For a symmetry-consistent theoretical description of this multiferroic phase, precise knowledge of its crystal structure is a prerequisite. Here we report the results of single-crystal neutron diffraction on Ca2CoSi2O7 at temperatures between 10 and 250 K. The low temperature structure at 10 K was refined assuming twinning in the orthorhombic space group P2(1)2(1)2 with a 3 * 3 * 1 supercell [a = 23.52 (1), b = 23.52 (1), c = 5.030 (3) A] compared with the high-temperature normal state [tetragonal space group P42(1)m, a = b ? 7.86, c ? 5.03 A]. The precise structural parameters of Ca2CoSi2O7 at 10 K are presented and compared with the literature X-ray diffraction results at 130 and 170 K (low-temperature commensurate phase), as well as at ~ 500 K (high-temperature normal phase). PMID- 26830805 TI - MmHn(XO4)(m + n)/2 crystals: structure, phase transitions, hydrogen bonds, conductivity. II. Structure and properties of Cs3(HSO4)2(H2PO4) and Cs4(HSO4)3(H2PO4) single crystals. AB - Cs3(HSO4)2(H2PO4) and Cs4(HSO4)3(H2PO4) single crystals were obtained for the first time based on a systematic study of the phase diagram of the CsHSO4-CsH2PO4 H2O ternary system. To reveal the structural conditionality for anomalies in physical properties, including dielectric and optical properties, diffraction studies of the crystal structure of Cs3(HSO4)2(H2PO4) and Cs4(HSO4)3(H2PO4) were performed, and their common structural features and differences were analyzed. PMID- 26830806 TI - Charge density of the biologically active molecule (2-oxo-1,3-benzoxazol-3(2H) yl)acetic acid. AB - (2-Oxo-1,3-benzoxazol-3(2H)-yl)acetic acid is a member of a biologically active class of compounds. Its molecular structure in the crystal has been determined by X-ray diffraction, and its gas phase structure was obtained by quantum chemical calculations at the B3LYP/6-311++G(d,p) level of theory. In order to understand the dynamics of the molecule, two presumably soft degrees of freedom associated with the relative orientation of the planar benzoxazolone system and its substituent at the N atom were varied systematically. Five conformers have been identified as local minima on the resulting two-dimensional potential energy surface within an energy window of 27 kJ mol(-1). The energetically most favourable minimum closely matches the conformation observed in the crystal. Based on high-resolution diffraction data collected at low temperature, the experimental electron density of the compound was determined. Comparison with the electron density established by theory for the isolated molecule allowed the effect of intermolecular interactions to be addressed, in particular a moderately strong O-H...O hydrogen bond with a donor...acceptor distance of 2.6177 (9) A: the oxygen acceptor is clearly polarized in the extended solid. The hydrogen bond connects consecutive molecules to chains, and the pronounced charge separation leads to stacking between neighburs with antiparallel dipole moments perpendicular to the chain direction. PMID- 26830807 TI - Variable-temperature single-crystal X-ray diffraction study of tetragonal and cubic perovskite-type barium titanate phases. AB - A variable-temperature single-crystal X-ray diffraction study of a synthetic BaTiO3 perovskite has been performed over the temperature range 298-778 K. A transition from a tetragonal (P4mm) to a cubic (Pm3m) phase has been revealed near 413 K. In the non-centrosymmetric P4mm symmetry group, both Ti and O atoms are displaced along the c-axis in opposite directions with regard to the Ba position fixed at the origin, so that Ti(4+) and Ba(2+) cations occupy off-center positions in the TiO6 and BaO12 polyhedra, respectively. Smooth temperature dependent changes of the atomic coordinates become discontinuous with the phase transition. Our observations imply that the cations remain off-center even in the high-temperature cubic phase. The temperature dependence of the mean-square displacements of Ti in the cubic phase includes a significant static component which means that Ti atoms are statistically distributed in the off-center positions. PMID- 26830808 TI - Structure-forming units of amino acid maleates. Case study of L-valinium hydrogen maleate. AB - A new salt of L-valinium hydrogen maleate was used as an example to study structure-forming units in amino acid maleates. This compound was crystallized, its structure solved from single-crystal X-ray diffraction data, and the phase purity of the bulk powder sample confirmed by X-ray powder diffraction and FT-IR spectra. The stability of the new salt was analyzed using density functional theory and PIXEL calculations with focus on the C(2)2(12) structure-forming crystallographic motif. This motif was of particular interest as it is common for almost all maleates. The exceptionally high ability of maleic acid to form salts with various amino acids was rationalized. PMID- 26830810 TI - Reduced withdrawal and failure rates of accelerated nursing students enrolled in pharmacology is associated with a supportive intervention. AB - BACKGROUND: To reduce nursing shortages, accelerated nursing programs are available for domestic and international students. However, the withdrawal and failure rates from these programs may be different than for the traditional programs. The main aim of our study was to improve the retention and experience of accelerated nursing students. METHODS: The academic background, age, withdrawal and failure rates of the accelerated and traditional students were determined. Data from 2009 and 2010 were collected prior to intervention. In an attempt to reduce the withdrawal of accelerated students, we set up an intervention, which was available to all students. The assessment of the intervention was a pre-post-test design with non-equivalent groups (the traditional and the accelerated students). The elements of the intervention were a) a formative website activity of some basic concepts in anatomy, physiology and pharmacology, b) a workshop addressing study skills and online resources, and c) resource lectures in anatomy/physiology and microbiology. The formative website and workshop was evaluated using questionnaires. RESULTS: The accelerated nursing students were five years older than the traditional students (p < 0.0001). The withdrawal rates from a pharmacology course are higher for accelerated nursing students, than for traditional students who have undertaken first year courses in anatomy and physiology (p = 0.04 in 2010). The withdrawing students were predominantly the domestic students with non-university qualifications or equivalent experience. The failure rates were also higher for this group, compared to the traditional students (p = 0.05 in 2009 and 0.03 in 2010). In contrast, the withdrawal rates for the international and domestic graduate accelerated students were very low. After the intervention, the withdrawal and failure rates in pharmacology for domestic accelerated students with non university qualifications were not significantly different than those of traditional students. CONCLUSIONS: The accelerated international and domestic graduate nursing students have low withdrawal rates and high success rates in a pharmacology course. However, domestic students with non-university qualifications have higher withdrawal and failure rates than other nursing students and may be underprepared for university study in pharmacology in nursing programs. The introduction of an intervention was associated with reduced withdrawal and failure rates for these students in the pharmacology course. PMID- 26830811 TI - Characterization of Cyclooxygenase-2 and its induction pathways in response to high lipid diet-induced inflammation in Larmichthys crocea. AB - The present study was conducted to investigate the effects of a high-lipid diet (HLD) on cyclooxygenase (Cox)-2 expression and the signalling pathways related to low-grade inflammation in the large yellow croaker (Larmichthys crocea). An isolated 2508 bp cDNA clone of cox-2 contained an open reading frame spanning 1827 bp encoding a protein with 608 amino acid residues. The over-expression of cox-2 was consistent with the activation of c-Jun N-terminal kinases (JNKs) and p38 mitogen-activated protein kinase (MAPK) in HLD-fed fish. The activation of the activator protein-1 (AP-1) and the nuclear transcription factor kappa-B (NF kappaB) signalling pathways in HLD-fed fish and the significant increase of cox-2 promoter-luciferase activity in vitro indicated that AP-1 and NF-kappaB could combine cox-2 promoter to promote its transcription, respectively. Together, HLD induced inflammation up-regulates cox-2 expression via JNKs and p38 MAPK dependent NF-kappaB and AP-1 pathways. The present study provides important insight into the signal transduction pathways involved in HLD-induced inflammation, which is detrimental to the health and production of fish as well as to the health of fish consumers. PMID- 26830812 TI - Tracking of autologous adipose tissue-derived mesenchymal stromal cells with in vivo magnetic resonance imaging and histology after intralesional treatment of artificial equine tendon lesions--a pilot study. AB - BACKGROUND: Adipose tissue-derived mesenchymal stromal cells (AT-MSCs) are frequently used to treat equine tendinopathies. Up to now, knowledge about the fate of autologous AT-MSCs after intralesional injection into equine superficial digital flexor tendons (SDFTs) is very limited. The purpose of this study was to monitor the presence of intralesionally injected autologous AT-MSCs labelled with superparamagnetic iron oxide (SPIO) nanoparticles and green fluorescent protein (GFP) over a staggered period of 3 to 9 weeks with standing magnetic resonance imaging (MRI) and histology. METHODS: Four adult warmblood horses received a unilateral injection of 10 * 10(6) autologous AT-MSCs into surgically created front-limb SDFT lesions. Administered AT-MSCs expressed lentivirally transduced reporter genes for GFP and were co-labelled with SPIO particles in three horses. The presence of AT-MSCs in SDFTs was evaluated by repeated examinations with standing low-field MRI in two horses and post-mortem in all horses with Prussian blue staining, fluorescence microscopy and with immunofluorescence and immunohistochemistry using anti-GFP antibodies at 3, 5, 7 and 9 weeks after treatment. RESULTS: AT-MSCs labelled with SPIO particles were detectable in treated SDFTs during each MRI in T2*- and T1-weighted sequences until the end of the observation period. Post-mortem examinations revealed that all treated tendons contained high numbers of SPIO- and GFP-labelled cells. CONCLUSIONS: Standing low-field MRI has the potential to track SPIO-labelled AT-MSCs successfully. Histology, fluorescence microscopy, immunofluorescence and immunohistochemistry are efficient tools to detect labelled AT-MSCs after intralesional injection into surgically created equine SDFT lesions. Intralesional injection of 10 * 10(6) AT-MSCs leads to the presence of high numbers of AT-MSCs in and around surgically created tendon lesions for up to 9 weeks. Integration of injected AT-MSCs into healing tendon tissue is an essential pathway after intralesional administration. Injection techniques have to be chosen deliberately to avoid reflux of the cell substrate injected. In vivo low field MRI may be used as a non-invasive tool to monitor homing and engraftment of AT-MSCs in horses with tendinopathy of the SDFT. PMID- 26830813 TI - Prevalence and associated factors of knee osteoarthritis in a rural Chinese adult population: an epidemiological survey. AB - BACKGROUND: The exact pathogenic mechanism of knee osteoarthritis (OA) is still unknown. With the exception of clinical treatment to alleviate symptoms, or total knee replacement, there is currently no effective treatment method. Consequently, an in-depth etiological and epidemiological study of knee OA can provide clues for diagnosis, treatment and scientific research, and will ultimately have a beneficial effect on public health. METHODS: A cross-sectional community study in the rural village of Gaoyou was conducted in 3428 Chinese adults (aged >= 40 years). Subjects completed an interviewer-administered questionnaire, evaluating knee pain and associated disability, analgesia, use of health services, past medical history, walking, income, smoking, and use of oral contraceptives, and standardized weight-bearing knee radiographs were obtained. Patient demographic characteristics and biochemical parameters were recorded. RESULTS: Single-factor regression analysis indicated that age, overweight, central adiposity, high low density lipoprotein cholesterol (LDLC), high total cholesterol (TC), high triglycerides (TG), dyslipidemia, hypertension and low income were the associated factors for knee OA in females; age, high LDLC, hypertension, low income and frequent walking were the associated factors for knee OA in males. Interestingly, male heavy smokers were less likely to develop severe knee OA compared with non smokers. Stepwise logistic regression analysis indicated that age and overweight were the associated factors for knee OA for all individuals. Although central adiposity, high LDLC, high TC, high TG, dyslipidemia, hypertension and low income appeared to be related to knee OA in females according to univariate analysis, these factors were not identified in stepwise logistic regression analysis. In addition although age, high LDLC, hypertension and frequent walking were also the associated factors for knee OA in males by stepwise logistic regression analysis, smoking as a protective factor was not identified in this analysis. CONCLUSIONS: In this study, aging, obesity, frequent walking, low income and relevant multiple metabolic disorders were the associated factors for knee OA. Smoking might be associated with a lower prevalence of OA in male smokers according to univariate analysis. A retrospective association of smoking with OA may constitute an important etiologic clue, but further well-designed, large-scale prospective controlled trials are required to confirm these findings. PMID- 26830815 TI - GP leaders vow to secure more money for general practice. PMID- 26830814 TI - The quality and diagnostic value of open narratives in verbal autopsy: a mixed methods analysis of partnered interviews from Malawi. AB - BACKGROUND: Verbal autopsy (VA), the process of interviewing a deceased's family or caregiver about signs and symptoms leading up to death, employs tools that ask a series of closed questions and can include an open narrative where respondents give an unprompted account of events preceding death. The extent to which an individual interviewer, who generally does not interpret the data, affects the quality of this data, and therefore the assigned cause of death, is poorly documented. We aimed to examine inter-interviewer reliability of open narrative and closed question data gathered during VA interviews. METHODS: During the introduction of VA data collection, as part of a larger study in Mchinji district, Malawi, we conducted partner interviews whereby two interviewers independently recorded open narrative and closed questions during the same interview. Closed questions were collected using a smartphone application (mobile InterVA) and open narratives using pen and paper. We used mixed methods of analysis to evaluate the differences between recorded responses to open narratives and closed questions, causes of death assigned, and additional information gathered by open narrative. RESULTS: Eighteen partner interviews were conducted, with complete data for 11 pairs. Comparing closed questions between interviewers, the median number of differences was 1 (IQR: 0.5-3.5) of an average 65 answered; mean inter-interviewer concordance was 92% (IQR: 92-99%). Discrepancies in open narratives were summarized in five categories: demographics, history and care-seeking, diagnoses and symptoms, treatment and cultural. Most discrepancies were seen in the reporting of diagnoses and symptoms (e.g., malaria diagnosis); only one pair demonstrated no clear differences. The average number of clinical symptoms reported was 9 in open narratives and 20 in the closed questions. Open narratives contained additional information on health seeking and social issues surrounding deaths, which closed questions did not gather. CONCLUSIONS: The information gleaned during open narratives was subject to inter-interviewer variability and contained a limited number of symptom indicators, suggesting that their use for assigning cause of death is questionable. However, they contained rich information on care-seeking, healthcare provision and social factors in the lead-up to death, which may be a valuable source of information for promoting accountable health services. PMID- 26830816 TI - A prospective, open-label, single arm, multicentre study to evaluate efficacy, safety and acceptability of pericoital oral contraception using levonorgestrel 1.5 mg. AB - STUDY QUESTION: Will the use of levonorgestrel (LNG) 1.5 mg taken at each day of coitus by women who have relatively infrequent sex be an efficacious, safe and acceptable contraceptive method? SUMMARY ANSWER: Typical use of LNG 1.5 mg taken pericoitally, before or within 24 h of sexual intercourse, provides contraceptive efficacy of up to 11.0 pregnancies per 100 women-years (W-Y) in the primary evaluable population and 7.1 pregnancies per 100 W-Y in the evaluable population. WHAT IS KNOWN ALREADY: LNG 1.5 mg is an effective emergency contraception following unprotected intercourse. Some users take it repeatedly, as their means of regular contraception. STUDY DESIGN, SIZE, DURATION: This was a prospective, open-label, single-arm, multicentre Phase III trial study with women who have infrequent coitus (on up to 6 days a month). Each woman had a follow-up visit at 2.5, 4.5 and 6.5 months after admission or until pregnancy occurs if sooner, or she decided to interrupt participation. The study was conducted between 10 January 2012 and 15 November 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 330 healthy fertile women aged 18-45 years at risk of pregnancy who reported sexual intercourse on up to 6 days a month, were recruited from four university centres located in Bangkok, Thailand; Campinas, Brazil; Singapore and Szeged, Hungary to use LNG 1.5 mg pericoitally (24 h before or after coitus) as their primary method of contraception. The participants were instructed to take one tablet every day she had sex, without taking more than one tablet in any 24-h period, and to maintain a paper diary for recording date and time for every coital act and ingestion of the study tablet, use of other contraceptive methods and vaginal bleeding patterns. Anaemia was assessed by haemoglobin evaluation. Pregnancy tests were performed monthly and pregnancies occurring during product use were assessed by ultrasound. At the 2.5-month and final visit at 6.5 months, acceptability questions were administered. MAIN RESULTS AND THE ROLE OF CHANCE: There were 321 women included in the evaluable population (which includes all eligible women enrolled), with 141.9 woman-years (W-Y) of observation and with a rate (95% confidence interval [CI]) of 7.1 (3.8; 13.1) pregnancies per 100 W-Y of typical use (which reflects use of the study drug as main contraceptive method, but also includes possible use of other contraceptives from admission to end of study) and 7.5 (4.0; 13.9) pregnancies per 100 W-Y of sole use. In the primary evaluable population (which includes only eligible enrolled women <35 years old), the rate was 10.3 (5.4; 19.9) pregnancies per 100 W-Y of typical use, and 11.0 (5.7; 13.1) pregnancies per 100 W-Y of sole use. There were three reported severe adverse events and 102 other mild adverse events (most common were headache, nausea, abdominal and pelvic pain), with high recovery rate. The vaginal bleeding patterns showed a slight decrease in volume of bleeding and the number of bleeding-free days increased over time. There was only one case of severe anaemia, found at the final visit (0.4%). The method was considered acceptable, as over 90% of participants would choose to use it in the future or would recommend it to others. LIMITATIONS, REASONS FOR CAUTION: This was a single-arm study with small sample size, without a control group, designed as a proof of concept study to explore the feasibility of this type of contraception. WIDER IMPLICATIONS OF THE FINDINGS: A larger clinical study evaluating pericoital contraception with LNG is feasible and our data show that this method would be acceptable to many women. STUDY FUNDING/COMPETING INTERESTS: This study received partial financial support from the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR) and the World Health Organization. Gynuity and the Bill and Melinda Gates Foundation (BMGF) provided financial support for project monitoring. HRA Pharma donated the LNG product. N.K. was the initial project manager when she was with WHO/HRP and was employed by HRA Pharma, which distributes LNG for emergency contraception. The other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: This study was registered on ANZCTR, Trial ID ACTRN12611001037998. TRIAL REGISTRATION DATE: 4 October 2011. DATE OF FIRST PATIENT'S ENROLMENT: 10 January 2012. PMID- 26830817 TI - UK Biobank's cardiovascular magnetic resonance protocol. AB - BACKGROUND: UK Biobank's ambitious aim is to perform cardiovascular magnetic resonance (CMR) in 100,000 people previously recruited into this prospective cohort study of half a million 40-69 year-olds. METHODS/DESIGN: We describe the CMR protocol applied in UK Biobank's pilot phase, which will be extended into the main phase with three centres using the same equipment and protocols. The CMR protocol includes white blood CMR (sagittal anatomy, coronary and transverse anatomy), cine CMR (long axis cines, short axis cines of the ventricles, coronal LVOT cine), strain CMR (tagging), flow CMR (aortic valve flow) and parametric CMR (native T1 map). DISCUSSION: This report will serve as a reference to researchers intending to use the UK Biobank resource or to replicate the UK Biobank cardiovascular magnetic resonance protocol in different settings. PMID- 26830819 TI - Current status of direct pulp-capping materials for permanent teeth. AB - Direct pulp-capping is a method for treating exposed vital pulp with dental material to facilitate the formation of reparative dentin and to maintain vital pulp. Two types of pulp-capping materials, calcium hydroxide and mineral trioxide aggregate, have been most commonly used in clinics, and an adhesive resin has been considered a promising capping material. However, until now, there has been no comprehensive review of these materials. Therefore, in this paper, the composition, working mechanisms and clinical outcome of these types of pulp capping materials are reviewed. PMID- 26830820 TI - Surface effects after a combination of dental bleaching and enamel microabrasion: An in vitro and in situ study. AB - This study evaluated the effects of combining enamel microabrasion and dental bleaching on the physical properties of enamel, using in vitro and in situ conditions and evaluating surface roughness, enamel microhardness and scanning electron microscopy images. One hundred sound bovine teeth were sectioned and cut into discs and randomly divided into 10 study groups (n=10). The results were submitted to Analysis of Variance (ANOVA) for repeated measures, followed by the Tukey test, with significance at 5%. Enamel surface roughness was significantly influenced by microabrasion, regardless of being combined with dental bleaching, for both HS (Human Saliva) or AS (Artificial Saliva) condition. Enamel microhardness was significantly decreased in the groups in which enamel microabrasion was performed, regardless its combination with dental bleaching; although storage in HS reestablished the initial enamel microhardness. It was concluded that dental bleaching does not cause major damage to microabraided enamel, and that only human saliva recovered the initial enamel microhardness. PMID- 26830818 TI - Challenges in the retrospective assessment of trauma: comparing a checklist approach to a single item trauma experience screening question. AB - BACKGROUND: Research on trauma and its impact on mental health typically relies on self-reports which can be influenced by recall bias and an individual's subjective interpretation of events. This study aims to compare responses on a checklist of life events with a trauma experience screening question, both of which assessed trauma experience retrospectively. METHODS: A community sample of adults were asked about life events from a checklist before asking them whether they ever had a trauma experience, i.e. "an event that either puts them or someone close to them at risk of serious harm or death". RESULTS: Less than half of the sample who reported at least one life event on the checklist that qualified as a trauma reported a trauma experience that they perceived put them or close others at risk of serious harm. Women responders, those reporting early life traumas, and a greater number of lifetime trauma events were more likely to report a trauma experience. Current symptoms of Common Mental Disorder did not account for differences in reporting of trauma experiences. CONCLUSIONS: Epidemiological approaches which require participants to make subjective judgement on the severity of the trauma experience will capture individual differences that we have shown are influenced by gender and previous trauma experience. PMID- 26830821 TI - Bonding effectiveness of self-adhesive and conventional-type adhesive resin cements to CAD/CAM resin blocks. Part 1: Effects of sandblasting and silanization. AB - The present study assessed the effect of sandblasting and silanization on resin cement bond strengths to CAD/CAM resin blocks. Twenty four blocks (KATANA AVENCIA BLOCK) were divided into two resin cement groups (PANAVIA V5 [PV5] and PANAVIA SA CEMENT HANDMIX [PSA]), and further divided into four subgroups representing different surface treatment methods: no treatment (Ctl), silanization (Si), sandblasting (Sb), and Sb+Si. After resin application, microtensile bond strengths (MUTBSs) were measured immediately, 1, 3 and 6 months after water storage. In addition, surfaces resulting from each of the treatment methods were analyzed by scanning electron microscopy (SEM). Three-way analysis of variance revealed a statistically significant effect for the parameters 'surface treatment' (p<0.001, F=370), 'resin cement' (p<0.001, F=103, PSA0.05) whereas the mean KIC from indentation techniques rarely agreed with those of the standard technique. The KIC determination is sensitive to the methods used that affect accuracy. Consequently, test selection should be based on a sound understanding and inherent limitations of each technique. PMID- 26830827 TI - Effect of dentin laser irradiation at different pulse settings on microtensile bond strength of flowable resin. AB - The aim of this study was to compare the effect of Er:YAG laser irradiation and adhesive systems on the microtensile bond strength (MUTBS) of flowable resin to dentin. The flat dentin surfaces of 30 wisdom molar teeth were randomly divided into 3 groups (n=10): no laser etching (control), laser etching using QSP and MSP modes. After the application of the flowable and the composite resin, and 5,000 thermal aging, the MUTBS results were analyzed with two-way analysis of variance and Tukey's honest standard of difference (HSD) tests. There were no significant differences between the MUTBS of the self-etch group and the total-etch groups for MSP (p>0.05). MSP mode is a useful pulse mode for dentin surface treatment due to elimination of the acid-etching step. PMID- 26830828 TI - Environmental SEM and dye penetration observation on resin-tooth interface using different light curing method. AB - The aim of this study was the effects of different light curing methods on marginal sealing and resin composite adaptation to the cavity wall using the dye penetration test and environmental scanning electron microscope (SEM) observations. Cylindrical cavities were prepared on cervical regions. The teeth were restored with Clearfil Liner Bond 2 V adhesive and filled with Clearfil Photo Bright or Palfique Estelite resin composites. These resins were cured with a conventional light-curing method or a slow-start curing method. After thermal cycling, the specimens were subjected to the dye penetration test to evaluate marginal sealing and adaptation of the resin composites to the cavity walls. These resin-tooth interfaces were then observed using environmental SEM. The light-cured resin composite, which exhibited increased contrast ratios during polymerization, suggests high compensation for polymerization stress using the slow-start curing method. There was a high correlation between dye penetration test and environmental SEM observation. PMID- 26830829 TI - Time-related surface modification of denture base acrylic resin treated by atmospheric pressure cold plasma. AB - The changes of denture base acrylic resin surface properties under cold plasma and the relationships with time were investigated. Cold plasma treated the specimens for 30 s, 60 s, 90 s, and 120 s, respectively. Water contact angles were measured immediately after the treatment, 48 h, 15 days and 30 days later. Surface roughness was measured with 3-D laser scanning microscope. Candida albicans adherence was evaluated by CFU counting. Chemical composition was monitored by X-ray photoelectron spectroscopy analysis. Water contact angle reduced after treated for 30 s. No changes were observed with time prolonged, except the durability. There were no differences in roughness among all groups. However, treatment groups showed significantly lower C. albicans adherence. XPS demonstrated a decrease in C/O, and this reduction was affected by treatment time. Cold plasma was an effective means of increasing hydrophilicity of acrylic resin and reducing C. albicans adherence without affecting physical properties. PMID- 26830830 TI - In vivo analyses of the effects of polyamidoamine dendrimer on dentin biomineralization and dentinal tubules occlusion. AB - This study evaluated the biomineralization and dentinal tubules occlusion abilities of the carboxyl-terminated polyamidoamine dendrimer (PAMAM-COOH) on human demineralized dentin in vivo at different time points. Demineralization dentin model with and without treated with PAMAM-COOH were sutured to the interior side of the rat's cheeks, that was incubated in the rats' saliva for 2, 4 and 6 weeks respectively. Finally, the newly formed precipitates were characterized by SEM, EDS, XRD and microhardness test. The hydroxyapatite (HA) on the dentin treated with PAMAM-COOH were formed gradually with the time going by, and the regenerated HA has a similar crystal structure with natural dentin, whereas the crystallites did not exist on the control group. The microhardness of PAMAM-COOH-applied specimens had a significantly higher than those without application. These results suggest that the PAMAM-COOH promoted the biomineralization of demineralized dentin and displayed favourable effects on blocking the open dentinal tubules. PMID- 26830831 TI - Chemical and morphological characteristics of mineral trioxide aggregate and Portland cements. AB - The purpose of this study was to investigate the chemical composition and particle morphology of white mineral trioxide aggregate (WMTA) and two white Portland cements (CEM 1 and CEM 2). Compositional analysis was performed by energy dispersive X-ray spectroscopy, X-ray fluorescence spectrometry and X-ray diffraction whereas, morphological characteristics were analyzed by scanning electron microscope and Laser scattering particle size distribution analyzer. The elemental composition of WMTA, CEM 1 and CEM 2 were similar except for the presence of higher amounts of bismuth in WMTA. Calcium oxide and silicon oxide constitute the major portion of the three materials whereas, tricalcium silicate was detected as the major mineral phase. The particle size distribution and morphology of WMTA was finer compared to CEM 1 and CEM 2. The three tested materials had relatively similar chemical composition and irregular particle morphologies. PMID- 26830832 TI - Bioactive treatment promotes osteoblast differentiation on titanium materials fabricated by selective laser melting technology. AB - Selective laser melting (SLM) technology is useful for the fabrication of porous titanium implants with complex shapes and structures. The materials fabricated by SLM characteristically have a very rough surface (average surface roughness, Ra=24.58 um). In this study, we evaluated morphologically and biochemically the specific effects of this very rough surface and the additional effects of a bioactive treatment on osteoblast proliferation and differentiation. Flat-rolled titanium materials (Ra=1.02 um) were used as the controls. On the treated materials fabricated by SLM, we observed enhanced osteoblast differentiation compared with the flat-rolled materials and the untreated materials fabricated by SLM. No significant differences were observed between the flat-rolled materials and the untreated materials fabricated by SLM in their effects on osteoblast differentiation. We concluded that the very rough surface fabricated by SLM had to undergo a bioactive treatment to obtain a positive effect on osteoblast differentiation. PMID- 26830833 TI - Efficacy of Twisted File Adaptive, Reciproc and ProTaper Universal Retreatment instruments for root-canal-filling removal: A cone-beam computed tomography study. AB - The aim of this study was to evaluate the efficacy of Twisted File (TF) Adaptive, Reciproc, and ProTaper Universal Retreatment (UR) System instruments for removing root-canal-filling. Sixty single rooted teeth were decoronated, instrumented and obturated. Preoperative CBCT scans were taken and the teeth were retreated with TF Adaptive, Reciproc, ProTaper UR, or hand files (n=15). Then, the teeth were rescanned, and the percentage volume of the residual root-canal-filling material was established. The total time for retreatment was recorded, and the data was statistically analyzed. The statistical ranking of the residual filling material volume was as follows: hand file=TF Adaptive>ProTaper UR=Reciproc. The ProTaper UR and Reciproc systems required shorter periods of time for retreatment. Root canal filling was more efficiently removed by using Reciproc and ProTaper UR instruments than TF Adaptive instruments and hand files. The TF Adaptive system was advantageous over hand files with regard to operating time. PMID- 26830834 TI - The effect of zirconia thickness and curing time on shear bond strength of dualcure resin cement. AB - This study evaluated how zirconia thickness affects shear bond strength (SBS) between zirconia and dual-cure resin cement. Eighty specimens (40 blocks of 1 mm thickness zirconia and 20 of each 1.5 and 2 mm) were divided into 8 groups according to zirconia thickness and light-curing time. Group A, B, C, and D were light-polymerized during 20 s and group E, F, G, and H were light-cured during 40 s. Self-adhesive dual-cure resin cement was placed onto the zirconia surfaces and then light-polymerized. The mean SBS of the 40 s curing time group was statistically higher than that of the 20 s curing time group. However, curing time did not affect the SBS significantly in the 2 mm thickness groups. The mean SBS of the 1.5 and 2 mm groups were statistically lower than those 1 mm groups. Therefore, zirconia thickness significantly affected the SBS of self-adhesive dual-cure resin cement. PMID- 26830835 TI - Effects of metal- and fiber-reinforced composite root canal posts on flexural properties. AB - The aim of this study was to observe the effects of different test conditions on the flexural properties of root canal post. Metal- and fiber-reinforced composite root canal posts of various diameters were measured to determine flexural properties using a threepoint bending test at different conditions. In this study, the span length/post diameter ratio of root canal posts varied from 3.0 to 10.0. Multiple regression models for maximum load as a dependent variable were statistically significant. The models for flexural properties as dependent variables were statistically significant, but linear regression models could not be fitted to data sets. At a low span length/post diameter ratio, the flexural properties were distorted by occurrence of shear stress in short samples. It was impossible to obtain high span length/post diameter ratio with root canal posts. The addition of parameters or coefficients is necessary to appropriately represent the flexural properties of root canal posts. PMID- 26830836 TI - Antibacterial capacity of cavity disinfectants against Streptococcus mutans and their effects on shear bond strength of a self-etch adhesive. AB - We evaluated the antibacterial properties of three disinfectants [2% chlorhexidine (CHX), 6% sodium hypochlorite (NaOCl), and 0.01% urushiol)] against Streptococcus mutans and their effects on bond strength of Scotchbond(TM) Universal. The reduction in bacterial growth was evaluated by the colony counting method. Total 105 specimens were assigned to seven groups, according to surface pretreatment: control group (C) without pretreatment; chlorhexidine gluconate with rinse (CR) or without rinse (CD); NaOCl with rinse (NR) or without rinse (ND); and urushiol with rinse (UR) or without rinse (UD). The shear bond test was performed at a cross-head speed of 0.5 mm/min. None of the disinfected specimens had viable microbes after a 30 min incubation. The control group exhibited the strongest bond; however, no significant difference was detected with the disinfectant-treated groups, except weak bonding with ND group. These findings suggest that all disinfectants tested had strong antibacterial capacity and may better be rinsed away. PMID- 26830837 TI - Mechanical versus manual chest compressions for cardiac arrest: a systematic review and meta-analysis. AB - BACKGROUND: The aim of this paper was to conduct a systematic review of the published literatures comparing the use of mechanical chest compression device and manual chest compression during cardiac arrest (CA) with respect to short term survival outcomes and neurological function. METHODS: Databases including MEDLINE, EMBASE, Web of Science and the ClinicalTrials.gov registry were systematically searched. Further references were gathered from cross-references from articles by handsearch. The inclusion criteria for this review must be human prospective controlled studies of adult CA. Random effects models were used to assess the risk ratios and 95% confidence intervals for return of spontaneous circulation (ROSC), survival to admission and discharge, and neurological function. RESULTS: Twelve trials (9 out-of-hospital and 3 in-hospital studies), involving 11,162 participants, were included in the review. The results of this meta-analysis indicated no differences were found in Cerebral Performance Category (CPC) scores, survival to hospital admission and survival to discharge between manual cardiopulmonary resuscitation (CPR) and mechanical CPR for out-of hospital CA (OHCA) patients. The data on achieving ROSC in both of in-hospital and out-of-hospital setting suggested poor application of the mechanical device (RR 0.71, [95% CI, 0.53, 0.97] and 0.87 [95% CI, 0.81, 0.94], respectively). OHCA patients receiving manual resuscitation were more likely to attain ROSC compared with load-distributing bands chest compression device (RR 0.88, [95% CI, 0.80, 0.96]). The in-hospital studies suggested increased relative harm with mechanical compressions for ratio of survival to hospital discharge (RR 0.54, [95% CI 0.29, 0.98]). However, the results were not statistically significant between different kinds of mechanical chest compression devices and manual resuscitation in survival to admission, discharge and CPC scores for OHCA patients and survival to discharge for in-hospital CA patients. CONCLUSIONS: The ability to achieve ROSC with mechanical devise was inferior to manual chest compression during resuscitation. The use of mechanical chest compression cannot be recommended as a replacement for manual CPR, but rather a supplemental treatment in an overall strategy for treating CA patients. PMID- 26830838 TI - Methicillin-resistant Staphylococcal periprosthetic joint infections can be effectively controlled by systemic and local daptomycin. AB - BACKGROUND: Methicillin-resistant Staphylococcus remains a serious problem in the treatment of periprosthetic joint infection (PJI). Higher failure rates were reported when vancomycin was used in 2-stage exchange arthroplasty. Therefore a better therapeutic drug is needed to treat PJI caused by methicillin-resistant organisms. The purpose of the study was to evaluate the safety and efficacy of daptomycin when administered in bone cement combined with systemic use for methicillin-resistant Staphylococci PJI. METHODS: We conducted a retrospective study from January 2010 to December 2012. Twenty-two patients (10 knees and 12 hips) with PJI caused by methicillin-resistant Staphylococcus species underwent 2 stage revision arthroplasty. In the first stage, 10% daptomycin (weight daptomycin per weight bone cement) was incorporated into polymethylmethacrylate bone cement, and systemic daptomycin (6 mg/kg) was administered postoperatively for 14 days. In the second stage, 2.5% w/w daptomycin was used in the bone cement. The minimum follow-up was 2 years or until recurrence of infection. RESULTS: The infecting organisms included methicillin-resistant Staphylococcus aureus in 10 patients, methicillin-resistant Staphylococcus epidermidis in 8 patients and methicillin-resistant coagulase-negative Staphylococci in 4 patients. The mean follow-up duration was 33.7 months (range, 24-51 months). The treatment success rate was 100%. Only one patient developed asymptomatic transient elevation of the creatine phosphokinase level. No patient experienced any adverse effects related to daptomycin such as myositis, rhabdomyolysis, peripheral neuropathy, derangement of liver function, or eosinophilic pneumonia. CONCLUSIONS: In this series, no serious adverse events occurred. Our protocol, using daptomycin-impregnated cement combined with short duration of systemic daptomycin, appears to be an effective and safe treatment for methicillin resistant Staphylococcus PJI. PMID- 26830839 TI - Predictors of Postoperative Wound Necrosis Following Primary Wound Closure of Open Ankle Fractures. AB - BACKGROUND: Most open malleolar ankle fracture wounds can be closed primarily after meticulous debridement. However, the development of wound necrosis following operative treatment of open malleolar ankle fractures can have catastrophic consequences. The aim of this study was to identify risk factors predisposing to postoperative wound necrosis following primary wound closure of open malleolar ankle fractures. METHODS: A total of 137 patients with open malleolar ankle fractures were identified. The open fracture wound was primarily closed in 110 of 137 (80%) patients, and postoperative wound necrosis occurred in 18 (16%) of these patients. These patients were compared to the open fracture patients without wound necrosis. Twenty possible risk factors for the development of wound necrosis were studied with logistic regression analysis. RESULTS: The variables that were independently associated with an increased risk for postoperative wound necrosis included ASA class >=2, Gustilo grade III open injury, and the use of pulsatile lavage at index surgery. CONCLUSIONS: Our study showed that ASA class >=2, Gustilo grade III open injury, and the use of pulsatile lavage at index surgery were the most important factors predisposing to postoperative wound necrosis following primary wound closure of open malleolar ankle fractures. The findings warrant a further study specifically comparing primary and delayed wound closure in patients with Gustilo grade III open malleolar ankle fractures and different ASA classes. Also, the role of pulsatile lavage should be re-evaluated. LEVEL OF EVIDENCE: Level III, retrospective comparative series. PMID- 26830840 TI - Virucidal activity of Haemaphysalis longicornis longicin P4 peptide against tick borne encephalitis virus surrogate Langat virus. AB - BACKGROUND: Longicin is a defensin-like peptide, identified from the midgut epithelium of hard tick Haemaphysalis longicornis. Several studies have already shown the antimicrobial and parasiticidal activities of longicin peptide and one of its synthetic partial analogs, longicin P4. In this study, longicin peptides were tested for potential antiviral activity against Langat virus (LGTV), a tick borne flavivirus. METHODS: Longicin P1 and P4 peptides were chemically synthesized. Antiviral activity of the longicin peptides against LGTV was evaluated through in vitro virucidal assays, wherein the antiviral efficacy was determined by reduction in number of viral foci and virus yield. Additionally, longicin P4 was also tested for its activity against human adenovirus, a non enveloped virus. Lastly, to assess the importance of longicin on the innate antiviral immunity of H. longicornis ticks, gene silencing through RNAi was performed. RESULTS: Longicin P4 produced significant viral foci reduction and lower virus yield against LGTV, while longicin P1 failed to demonstrate the same results. Conversely, both longicin partial analogs (P1 and P4) did not show significant antiviral activity when tested on adenovirus. In addition, longicin silenced ticks showed significantly higher virus titer after 7 days post infection but a significantly lower titer was detected after an additional 14 days of observation as compared to the Luc dsRNA-injected ticks. Mortality in both groups did not show any significant difference. CONCLUSION: Our results suggest that longicin P4 has in vitro antiviral activity against LGTV but not against a non-enveloped virus such as adenovirus. Likewise, though most cationic antimicrobial peptides like longicin act directly on target membranes, the exact mechanism of membrane targeting of longicin P4 in enveloped viruses, such as LGTV, requires further investigation. Lastly, while the in vitro virucidal capacity of longicin P4 was confirmed in this study, the role of the endogenous tick longicin in the antiviral defense of H. longicornis against LGTV still remains to be demonstrated. PMID- 26830841 TI - Apolipoprotein E polymorphism and the risk of intracranial aneurysms in a Chinese population. AB - BACKGROUND: The relationship between the apolipoprotein E (APOE) polymorphism and intracranial aneurysms has previously only been studied in Russia and Japan but not in Chinese populations. The purpose of this study was to investigate the association between APOE polymorphism and the risk of intracranial aneurysms in a Chinese population. METHODS: The study population consisted of 150 intracranial aneurysms patients and 150 matched control subjects. The APOE gene polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Patients with intracranial aneurysms had a significantly higher frequency of APOE E2/E2 genotype [odds ratio (OR) = 9.51, 95% confidence interval (CI) = 1.19, 76.04; P = 0.03] and APOE E2/E3 genotype (OR = 1.87, 95% CI = 1.03, 3.40; P = 0.04) than healthy controls. The APOE E4/E4 genotype frequencies (OR = 0.09, 95% CI = 0.01, 0.74; P = 0.03) in the intracranial aneurysms group were significantly lower than those in the controls group. When stratified by the site, shape, size and the Fisher Grade of intracranial aneurysms, no statistically significant result was observed. CONCLUSION: Our study suggested that APOE polymorphism might be associated with intracranial aneurysms in Chinese population. Additional studies are needed to confirm this finding. PMID- 26830842 TI - Persistent oral health disparity in 12-year-old Hispanics: a cross-sectional study. AB - BACKGROUND: Dental caries is the most prevalent chronic illness worldwide. In the US dental caries has been described as a "silent epidemic", affecting 58.2 % of 12-15 year-olds, particularly in minority and immigrant groups. Caries is associated with complex yet preventable biological and behavioral factors such as dental plaque and diet, as well as social determinants of health. In developed nations, a higher risk caries has been associated with populations of low socio economic status (SES), especially in areas with greater income disparity. An island-wide study conducted in Puerto Rico in 1997 revealed a high prevalence of dental caries in 12-year-olds and a significant health disparity between children attending private and public schools. The purpose of the present study was twofold: 1) to estimate caries levels of 12-year-old school Puerto Ricans in 2011; and 2) compare results to data obtained in 1997 to explore any possible change in caries outcomes after a government health insurance (GHI) reform was implemented. METHODS: In this cross-sectional study, a probability sample of 133 out of 1,843 schools was selected proportional to enrollment size, and stratified by 1997 GHI regions, school type, and gender. Calibrated examiners conducted oral soft tissue and caries examinations. Dental caries prevalence was estimated. Mean Decayed Missing Filled Tooth/Surface (DMFT/S) indices and mean Significant Caries Index (SiC) were calculated and compared retrospectively to data obtained in 1997. RESULTS: The final sample included 1,587 school-enrolled children. About 53 % of participants were female and 77 % attended public schools. Between 1997 and 2011, reductions were observed in caries prevalence (81 to 69 %), mean DMFT scores (3.8 to 2.5), mean DMFS scores (6.5 to 3.9), and mean SiC index (7.3 to 5.6) in both private and public schools, with a more prominent decrease in private schools. Between 1997 and 2011, overall the filled component increased (50 to 67 %), while decayed and missing component decreased (42 to 30 %) and (8 to 3 %), respectively. CONCLUSIONS: Among 12-year-old schoolchildren in Puerto Rico between 1997 and 2011, caries prevalence, extent, and severity decreased as well as the DMFT missing component, while the filled component increased. Dental caries prevalence was high and the health disparity persists between children enrolled in public and private schools after more than a decade of the GHI implementation. The relationship between GHI implementation and other potentially relevant co-factors for caries warrants further research, as does the seemingly entrenched disparity across groups. PMID- 26830843 TI - Comparison of breast sequential and simultaneous integrated boost using the biologically effective dose volume histogram (BEDVH). AB - PURPOSE: A method is presented to radiobiologically compare sequential (SEQ) and simultaneously integrated boost (SIB) breast radiotherapy. METHODS: The method is based on identically prescribed biologically effective dose (iso-BED) which was achieved by different prescribed doses due to different fractionation schemes. It is performed by converting the calculated three-dimensional dose distribution to the corresponding BED distribution taking into consideration the different number of fractions for generic alpha/beta ratios. A cumulative BED volume histogram (BEDVH) is then derived from the BED distribution and is compared for the two delivery schemes. Ten breast cancer patients (4 right-sided and 6 left-sided) were investigated. Two tangential intensity modulated whole breast beams with two other oblique (with different gantry angles) beams for the boost volume were used. The boost and the breast target volumes with either alpha/beta = 10 or 3 Gy, and ipsi-lateral and contra-lateral lungs, heart, and contra-lateral breast as organs at risk (OARs) with alpha/beta = 3 Gy were compared. RESULTS: Based on the BEDVH comparisons, the use of SIB reduced the biological breast mean dose by about 3 %, the ipsi-lateral lung and heart by about 10 %, and contra-lateral breast and lung by about 7 %. CONCLUSION: BED based comparisons should always be used in comparing plans that have different fraction sizes. SIB schemes are dosimetrically more advantageous than SEQ in breast target volume and OARs for equal prescribed BEDs for breast and boost. PMID- 26830844 TI - New and emerging medical therapies in Parkinson's disease. AB - INTRODUCTION: Parkinson's disease (PD) is one of the most challenging neurodegenerative disorders to treat as it manifests with a large variety of troublesome, and often disabling, motor and non-motor symptoms. Despite limitations, such as motor and other complications, levodopa remains the most effective drug in the treatment of PD. AREAS COVERED: In this review, we focus on phase 2 and 3 studies describing new and emerging medical therapies in PD. We discuss new formulations of levodopa, medications that prolong levodopa response and ameliorate levodopa-induced dyskinesias, and innovative delivery methods that are currently being evaluated in clinical trials or are in development with the promise of better efficacy and tolerability. We also describe novel non dopaminergic drugs that have been identified for treatment of motor and non-motor symptoms. A specific section is designated for potential disease modifying therapies. EXPERT OPINION: Alternative formulations of levodopa appear to be promising especially to help with the motor fluctuations either by providing sustained benefits with controlled released formulations or ameliorate sudden OFF by formulations such as inhaled levodopa. Several different medications affecting non-dopaminergic pathways are being evaluated which may aide levodopa. As the understanding of the disease grows further, numerous novel neuroprotective or disease modifying therapies have been suggested. This along with development of medications to treat various non-motor symptoms will help improve quality of life of patients with PD. PMID- 26830846 TI - NEAT: a framework for building fully automated NGS pipelines and analyses. AB - BACKGROUND: The analysis of next generation sequencing (NGS) has become a standard task for many laboratories in the life sciences. Though there exists several tools to support users in the manipulation of such datasets on various levels, few are built on the basis of vertical integration. Here, we present the NExt generation Analysis Toolbox (NEAT) that allows non-expert users including wet-lab scientists to comprehensively build, run and analyze NGS data through double-clickable executables without the need of any programming experience. RESULTS: In comparison to many publicly available tools including Galaxy, NEAT provides three main advantages: (1) Through the development of double-clickable executables, NEAT is efficient (completes within <24 hours), easy to implement and intuitive; (2) Storage space, maximum number of job submissions, wall time and cluster-specific parameters can be customized as NEAT is run on the institution's cluster; (3) NEAT allows users to visualize and summarize NGS data rapidly and efficiently using various built-in exploratory data analysis tools including metagenomic and differentially expressed gene analysis. To simplify the control of the workflow, NEAT projects are built around a unique and centralized file containing sample names, replicates, conditions, antibodies, alignment-, filtering- and peak calling parameters as well as cluster-specific paths and settings. Moreover, the small-sized files produced by NEAT allow users to easily manipulate, consolidate and share datasets from different users and institutions. CONCLUSIONS: NEAT provides biologists and bioinformaticians with a robust, efficient and comprehensive tool for the analysis of massive NGS datasets. Frameworks such as NEAT not only allow novice users to overcome the increasing number of technical hurdles due to the complexity of manipulating large datasets, but provide more advance users with tools that ensure high reproducibility standards in the NGS era. NEAT is publically available at https://github.com/pschorderet/NEAT. PMID- 26830847 TI - Altered rainfall patterns increase forb abundance and richness in native tallgrass prairie. AB - Models predict that precipitation variability will increase with climate change. We used a 15-year precipitation manipulation experiment to determine if altering the timing and amount of growing season rainfall will impact plant community structure in annually burned, native tallgrass prairie. The altered precipitation treatment maintained the same total growing season precipitation as the ambient precipitation treatment, but received a rainfall regime of fewer, larger rain events, and longer intervals between events each growing season. Although this change in precipitation regime significantly lowered mean soil water content, overall this plant community was remarkably resistant to altered precipitation with species composition relatively stable over time. However, we found significantly higher forb cover and richness and slightly lower grass cover on average with altered precipitation, but the forb responses were manifest only after a ten-year lag period. Thus, although community structure in this grassland is relatively resistant to this type of altered precipitation regime, forb abundance in native tallgrass prairie may increase in a future characterized by increased growing season precipitation variability. PMID- 26830848 TI - Age-related effects of chronic restraint stress on ethanol drinking, ethanol induced sedation, and on basal and stress-induced anxiety response. AB - Adolescents are sensitive to the anxiolytic effect of ethanol, and evidence suggests that they may be more sensitive to stress than adults. Relatively little is known, however, about age-related differences in stress modulation of ethanol drinking or stress modulation of ethanol-induced sedation and hypnosis. We observed that chronic restraint stress transiently exacerbated free-choice ethanol drinking in adolescent, but not in adult, rats. Restraint stress altered exploration patterns of a light-dark box apparatus in adolescents and adults. Stressed animals spent significantly more time in the white area of the maze and made significantly more transfers between compartments than their non-stressed peers. Behavioral response to acute stress, on the other hand, was modulated by prior restraint stress only in adults. Adolescents, unlike adults, exhibited ethanol-induced motor stimulation in an open field. Stress increased the duration of loss of the righting reflex after a high ethanol dose, yet this effect was similar at both ages. Ethanol-induced sleep time was much higher in adult than in adolescent rats, yet stress diminished ethanol-induced sleep time only in adults. The study indicates age-related differences that may increase the risk for initiation and escalation in alcohol drinking. PMID- 26830850 TI - Human embryonic cardiovascular function. AB - INTRODUCTION: This review presents an overview of descriptive knowledge on human embryonic cardiovascular physiology mostly based on noninvasive assessment by Doppler ultrasonography. Our objective was to identify and analyze published studies on embryonic cardiovascular function, and summarize available knowledge in this field. MATERIAL AND METHODS: Citations related to human embryonic cardiovascular function were searched in PubMed, EMBASE, CINAHL and Web of Science using keywords and MeSH terms without any time limitation. The search was restricted to English language articles. Abstracts were screened and full texts of relevant articles were obtained. All articles that reported on physiological aspects of human embryonic cardiovascular function were included. Studies reporting on cardiovascular function after 10 weeks of gestation were excluded. Data were synthesized and presented narratively. RESULTS: We identified 10 studies that had evaluated cardiovascular function and/or hemodynamics in human embryos at <=10 weeks of gestation. All of these reported only certain aspects of embryonic cardiovascular function. Embryonic heart rate is associated significantly with gestational age and increases from 6 to 10 weeks of gestation. Cardiac inflow is monophasic during the embryonic period and atria appear to generate higher force during contraction compared with ventricles. Both ventricular inflow and outflow velocities increase with advancing gestation, whereas the Tei index decreases significantly. During the embryonic period, placental blood flow increases with gestation, but absent umbilical artery diastolic flow and umbilical venous pulsations are normal phenomena. CONCLUSION: There are important differences in normal cardiovascular function between the embryonic and fetal stages of human in utero development. PMID- 26830849 TI - MicroRNA-181b Improves Glucose Homeostasis and Insulin Sensitivity by Regulating Endothelial Function in White Adipose Tissue. AB - RATIONALE: The pathogenesis of insulin resistance involves dysregulated gene expression and function in multiple cell types, including endothelial cells (ECs). Post-transcriptional mechanisms such as microRNA-mediated regulation of gene expression could affect insulin action by modulating EC function. OBJECTIVE: To determine whether microRNA-181b (miR-181b) affects the pathogenesis of insulin resistance by regulating EC function in white adipose tissue during obesity. METHODS AND RESULTS: MiR-181b expression was reduced in adipose tissue ECs of obese mice, and rescue of miR-181b expression improved glucose homeostasis and insulin sensitivity. Systemic intravenous delivery of miR-181b robustly accumulated in adipose tissue ECs, enhanced insulin-mediated Akt phosphorylation at Ser473, and reduced endothelial dysfunction, an effect that shifted macrophage polarization toward an M2 anti-inflammatory phenotype in epididymal white adipose tissue. These effects were associated with increased endothelial nitric oxide synthase and FoxO1 phosphorylation as well as nitric oxide activity in epididymal white adipose tissue. In contrast, miR-181b did not affect insulin-stimulated Akt phosphorylation in liver and skeletal muscle. Bioinformatics and gene profiling approaches revealed that Pleckstrin homology domain leucine-rich repeat protein phosphatase, a phosphatase that dephosphorylates Akt at Ser473, is a novel target of miR-181b. Knockdown of Pleckstrin homology domain leucine-rich repeat protein phosphatase increased Akt phosphorylation at Ser473 in ECs, and phenocopied miR 181b's effects on glucose homeostasis, insulin sensitivity, and inflammation of epididymal white adipose tissue in vivo. Finally, ECs from diabetic subjects exhibited increased Pleckstrin homology domain leucine-rich repeat protein phosphatase expression. CONCLUSIONS: Our data underscore the importance of adipose tissue EC function in controlling the development of insulin resistance. Delivery of miR-181b or Pleckstrin homology domain leucine-rich repeat protein phosphatase inhibitors may represent a new therapeutic approach to ameliorate insulin resistance by improving adipose tissue endothelial Akt-endothelial nitric oxide synthase-nitric oxide signaling. PMID- 26830852 TI - New oral anticoagulants - a guide for ENT surgeons. AB - BACKGROUND: New oral anticoagulants have been developed to overcome the perceived disadvantages of more traditional anticoagulants such as heparin and warfarin, and their use amongst ENT patients have been increasing. OBJECTIVES: This review article aims to discuss the mechanism of action of new oral anticoagulants, when they should be used and a protocol for their use, in both the bleeding patient and in the peri-operative setting. CONCLUSION: It is important that ENT surgeons are aware of the use of new oral anticoagulants, and have a departmental- and trust-based policy on their use and reversal in bleeding and surgical patients. PMID- 26830851 TI - Current indications for hip resurfacing arthroplasty in 2016. AB - Hip resurfacing arthroplasty (HRA) is an alternative to conventional, stemmed total hip arthroplasty (THA). The best reported results are young, active patients with good bone stock and a diagnosis of osteoarthritis. Since the 1990s, metal-on-metal (MoM) HRA has achieved excellent outcomes when used in the appropriate patient population. Concerns regarding the metal-on-metal bearing surface including adverse local tissue reaction (ALTR) to metal debris have recently lead to a decline in the use of this construct. The current paper aims to provide an updated review on HRA, including a critical review of the most recent literature on HRA. PMID- 26830853 TI - Diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) in the treatment of irritable bowel syndrome: indications and design. AB - In recent years, there has been growing interest in diet low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) as an important mainstay in the treatment of irritable bowel syndrome (IBS). This model of diet was developed by a multidisciplinary team from the Monash University in Melbourne and became well-known after the publication of a study in 2008 showing that dietary FODMAPs acted as causing factors in patients with IBS. Since then there have been several randomized controlled trials which, although with small sample sizes, have again shown the benefits of this dietary pattern. PMID- 26830854 TI - Baseline ALT levels as a marker of glycemic response to treatment with GLP-1 receptor agonists. AB - BACKGROUND AND OBJECTIVES: This study aimed to assess if ALT levels, as a marker of non-alcoholic fatty liver disease, may predict HbA1c response to treatment with GLP-1 receptor agonists (GLP-1 RAs). PATIENTS AND METHODS: A retrospective, longitudinal, analytical study was conducted including patients with type 2 diabetes mellitus continuously treated with GLP-1 agonists (85% with liraglutide) for one year. Patients were divided into two groups according to baseline ALT levels, with 24 U/L (the median of the distribution) as the cut-off point. The dependent variable was HbA1c change (one-year follow-up minus baseline). The predictive value of ALT levels above 24 U/L and ALT change was analyzed using multivariate linear regression adjusted to age, gender, diabetes duration, type and dose of GLP-1 RA, baseline HbA1c, baseline body mass index (BMI), and change in BMI. RESULTS: A total of 117 patients (48% females) aged 58.6 (SD 9.6) years were enrolled into the study. Treatment was associated with a change in ALT of 4.3 U/L (p=0.041) and a change in HbA1c of -1.1% (p<0.0001). Decreases in HbA1c ( 1.41% vs -0.76%; p=0.045) and ALT (-9.25 vs 0.46 U/L; p=0.002) were significantly higher in patients with ALT levels above the median. In the multivariate analysis, both ALT>24 U/L (b=-0.74; 95%CI: -1.31 to -0.18; p=0.011) and ALT change (b=0.028; 95%CI: 0.010 to 0.046; p=0.003), were significant response predictors. CONCLUSIONS: Elevated baseline transaminase values and decreased transaminase levels during follow-up are associated to a favorable glycemic response to GLP-1 RAs. PMID- 26830856 TI - Type 2 diabetes mellitus disease risk genes identified by genome wide copy number variation scan in normal populations. AB - AIMS: To identify the role of copy number variations (CNVs) on disease risk genes and its effect on disease phenotypes in type 2 diabetes mellitus (T2DM) in 12 random populations using high throughput arrays. METHODS: CNV analysis was carried out on a total of 1715 individuals from 12 populations, from ArrayExpress Archive of the European Bioinformatics Institute along with our subjects using Affymetrix Genome Wide SNP 6.0 array. CNV effect on T2DM genes were analyzed using several bioinformatics tools and a molecular protein interaction network was constructed to identify the disease mechanism altered by the CNVs. RESULTS: Analysis showed 34.4% of the total population to be under CNV burden for T2DM, with 83 disease causal and associated genes being under CNV influence. Hotspots were identified on chromosomes 22, 12, 6, 19 and 11.Overlap studies with case cohorts revealed significant disease risk genes such as EGFR, E2F1, PPP1R3A, HLA and TSPAN8. CONCLUSIONS: CNVs play a significant role in predisposing T2DM in normal cohorts and contribute to the phenotypic effects. Thus, CNVs should be considered as one of the major contributors in predisposition of the disease. PMID- 26830855 TI - NerveCheck: An inexpensive quantitative sensory testing device for patients with diabetic neuropathy. AB - AIMS: Sensory neuropathy is central to the development of painful neuropathy, and foot ulceration in patients with diabetes. Currently, available QST devices take considerable time to perform and are expensive. NerveCheck is the first inexpensive ($500), portable QST device to perform both vibration and thermal testing and hence evaluate diabetic peripheral neuropathy (DPN). This study was undertaken to establish the reproducibility and diagnostic validity of NerveCheck for detecting neuropathy. METHODS: 130 subjects (28 with DPN, 46 without DPN and 56 control subjects) underwent QST assessment with NerveCheck; vibration perception and thermal testing. DPN was defined according to the Toronto criteria. RESULTS: NerveCheck's intra correlation coefficient for vibration, cold and warm sensation testing was 0.79 (95% LOA: -4.20 to 6.60), 0.86 (95% LOA: 1.38 to 2.72) and 0.71 (95% LOA: -2.36 to 3.83), respectively. The diagnostic accuracy (AUC) for vibration, cold and warm sensation testing was 86% (SE: 0.038, 95% CI 0.79-0.94), 79% (SE: 0.058, 95% CI 0.68-0.91) and 72% (SE: 0.058, 95% CI 0.60-0.83), respectively. CONCLUSIONS: This study shows that NerveCheck has good reproducibility and comparable diagnostic accuracy to established QST equipment for the diagnosis of DPN. PMID- 26830857 TI - Health related quality of life and family impact of type 1 diabetes among adolescents in Saudi Arabia. AB - AIM: To measure the health related quality of life (HRQoL) among Saudi Arabian adolescents with type 1 diabetes mellitus (T1DM) and the impact the disease has on the family. METHODOLOGY: A cross sectional study was conducted involving 315 adolescent patients (12-18 years) and their caregivers. Adolescent HRQoL was assessed by adolescents and their parents completing the Peds QLTM Diabetes Module 3.0. Family impact was assessed by the parent completing the Peds QLTM Family Impact module (FIM). RESULTS: Adolescents reported a cumulative mean HRQoL score of 64.8, while parents reported significantly lower scores of 60.3 (p=0.003). The lowest scores reported by both adolescents and parents were for "Worry". Female gender and late adolescent age were predictors of lower HRQoL for adolescents with T1DM. The FIM showed low scores for "Emotional functioning" (59.8) and high scores for "Family relationships" (80.9). CONCLUSION: These findings emphasize the importance of an interdisciplinary, biopsychosocial and family centered care approach to adolescents with a chronic disease. Future work could assess the effectiveness of direct care involvement of adolescent and mental health experts in improving the HRQoL for this population. PMID- 26830858 TI - Ulcero-osteolytic lesions in a woman with type 2 diabetes and carpal tunnel syndrome: A case report and literature review. AB - We describe the case of a 73-year-old woman with type 2 diabetes presenting with ulcers and ostelytic lesions on distal phalanges of left hand, who was diagnosed with the rare "ulcero-mutilating" variant of carpal tunnel syndrome. A review of literature on cutaneous manifestations associated with the syndrome is also presented. PMID- 26830859 TI - Novel flow cytometric approach for the detection of adipocyte subpopulations during adipogenesis. AB - The ability of mesenchymal stromal cells (MSCs) to differentiate into adipocytes provides a cellular model of human origin to study adipogenesis in vitro. One of the major challenges in studying adipogenesis is the lack of tools to identify and monitor the differentiation of various subpopulations within the heterogeneous pool of MSCs. Cluster of differentiation (CD)36 plays an important role in the formation of intracellular lipid droplets, a key characteristic of adipocyte differentiation/maturation. The objective of this study was to develop a reproducible quantitative method to study adipocyte differentiation by comparing two lipophilic dyes [Nile Red (NR) and Bodipy 493/503] in combination with CD36 surface marker staining. We identified a subpopulation of adipose derived stromal cells that express CD36 at intermediate/high levels and show that combining CD36 cell surface staining with neutral lipid-specific staining allows us to monitor differentiation of adipose-derived stromal cells that express CD36(intermediate/high)during adipocyte differentiation in vitro. The gradual increase of CD36(intermediate/high/)NR(positive)cells during the 21 day adipogenesis induction period correlated with upregulation of adipogenesis associated gene expression. PMID- 26830861 TI - Variability in Endogenous Perfusion Recovery of Immunocompromised Mouse Models of Limb Ischemia. AB - Immunocompromised hind limb ischemia (HLI) murine models are essential for preclinical evaluation of human cell-based therapy or biomaterial-based interventions. These models are used to generate proof of principle that the approach is effective and also regulatory preclinical data required for translation to the clinic. However, surgical variations in creation of HLI models reported in the literature introduce variability in the pathological manifestation of the model, in consequence affecting therapeutic endpoints. This study aims to compare the extent of vascular regeneration in HLI-induced immunocompromised murine models to obtain a stable and more reproducible injury model for testing. Athymic and Balb/C nude mice underwent HLI surgery with single and double ligation of femoral artery (FA). The recovery from surgery was observed over a period of 2 weeks with respect to ischemia reperfusion using laser Doppler and clinical signs of necrosis and ambulatory impairment. Double ligation of the FA results in a more severe response to ischemia in Balb/C with endogenous perfusion recovery up to 50% +/- 10% compared with 75% +/- 20% in athymic nude mice. Single iliac artery (IA) and FA lead to creation of mild ischemia compared with femoral artery-vein (FAV) pair ligation in Balb/C. Microcirculatory parameters indicate significantly lower capillary numbers (26 +/ 3/mm(2)) and functional capillary density (203 +/- 5 cm/cm(2)) in the FAV group. In this study, we demonstrate a reproducible, arterial double ligation in an immunocompromised Balb/C nude mouse model that exhibits characteristic pathological signs of ischemia with impaired endogenous recovery. PMID- 26830860 TI - A novel lysophosphatidylcholine acyl transferase activity is expressed by peroxiredoxin 6. AB - The phospholipase A2(PLA2) activity of peroxiredoxin (Prdx)6 has important physiological roles in the synthesis of lung surfactant and in the repair of peroxidized cell membranes. These functions require the activity of a lysophospholipid acyl transferase as a critical component of the phospholipid remodeling pathway. We now describe a lysophosphatidylcholine acyl transferase (LPCAT) activity for Prdx6 that showed a strong preference for lysophosphatidylcholine (LPC) as the head group and for palmitoyl CoA in the acylation reaction. The calculated kinetic constants for acylation wereKm18 MUM andVmax30 nmol/min/mg protein; theVmaxwas increased 25-fold by phosphorylation of the protein whileKmwas unchanged. Study of recombinant protein in vitro and in mouse pulmonary microvascular endothelial cells infected with a lentiviral vector construct indicated that amino acid D31 is crucial for LPCAT activity. A linear incorporation of labeled fatty acyl CoA into dipalmitoyl phosphatidylcholine (PC) indicated that LPC generated by Prdx6 PLA2activity remained bound to the enzyme for the reacylation reaction. Prdx6 is the first LPCAT enzyme with demonstrated cytoplasmic localization. Thus, Prdx6 is a complete enzyme comprising both PLA2and LPCAT activities for the remodeling pathway of PC synthesis or for repair of membrane lipid peroxidation. PMID- 26830862 TI - Comparison of half- and standard-dose ticagrelor in Chinese patients with NSTE ACS. AB - Ticagrelor is a novel direct-acting P2Y12 receptor antagonist used for preventing atherothrombotic events in patients with acute coronary syndromes (ACS). The current recommended dose is 90 mg bid, but a low dose of ticagrelor has not been previously studied in Chinese ACS patients. Therefore, we performed this study to observe the different effects of half- and standard-dose ticagrelor on platelet aggregation in Chinese patients with NSTE-ACS. Sixty-two NSTE-ACS subjects were assigned to half-dose ticagrelor (n = 20), standard-dose ticagrelor (n = 22) and clopidogrel (n = 20) groups. Five days after drug administration, VerifyNow P2Y12 assay was performed to test P2Y12 reaction units (PRU) and inhibition of platelet aggregation (IPA). High-platelet reactivity (HPR) was defined as a PRU > 208. The adverse events, including bleeding events and dyspnoea, were monitored throughout the study. PRU values in the half-dose (44.55 +/- 32.88) and standard-dose (39.10 +/- 40.02) ticagrelor were dramatically lower than those in the clopidogrel group (189.20 +/- 65.22; P < 0.0001). The half-dose (84% +/- 10%) and standard-dose (86% +/- 13%) ticagrelor both showed greater IPA than clopidogrel (33% +/- 20%; P < 0.0001). There were no significant differences in PRU and IPA between the two ticagrelor groups (P = 0.3085 and 0.4028, respectively). HPR rates were significantly lower in the two ticagrelor groups (0% for both) than those in the clopidogrel group (35%). In conclusion, half-dose ticagrelor had a similar inhibitory effect on platelet aggregation as standard-dose ticagrelor in Chinese patients with NSTE-ACS, which was significantly stronger than that of clopidogrel. PMID- 26830863 TI - Right fronto-insular white matter tracts link cognitive reserve and pain in migraine patients. AB - BACKGROUND: Structural white matter abnormalities in pain-modulating, regions are present in migraine. Whether they are associated with pain chronification and with cognitive reserve is unclear. METHODS: Prospective, cohort, six-month study of adult patients with episodic or chronic migraine, and controls. Cognitive reserve, quality of life, impact of pain on daily living, depression and anxiety were assessed. Participants underwent a diffusion-tensor MRI to establish the integrity of white matter tracts of three regions of interest (ROIs) implicated in pain modulation, emotion, cognition and resilience (anterior insula, anterior cingulate gyrus, and uncinate fasciculus). RESULTS: Fifty-two individuals were enrolled: 19 episodic migraine patients, 18 chronic migraine patients, and 15 controls. The analysis of the fractional anisotropy in the ROIs showed that those patients with the poorest prognosis (i.e., those with chronic migraine despite therapy at six months--long-term chronic migraneurs) had a significantly lower fractional anisotropy in the right ROIs. Participants with higher cognitive reserve also had greater fractional anisotropy in the right anterior insula and both cingulate gyri. Multivariate analysis showed a significant association between cognitive reserve, migraine frequency, and fractional anisotropy in the right-sided regions of interest. CONCLUSIONS: Long-term chronic migraine patients show abnormalities in anterior white matter tracts, particularly of the right hemisphere, involved in pain modulation emotion, cognition and resilience. Robustness in these areas is associated with a higher cognitive reserve, which in turn might result in a lower tendency to migraine chronification. PMID- 26830864 TI - Clustering of autoimmune diseases in patients with rosacea. AB - BACKGROUND: Rosacea is a common inflammatory skin condition that shares genetic risk loci with autoimmune diseases such as type 1 diabetes mellitus (T1DM) and celiac disease. A recent genomewide association study identified 90 genetic regions associated with T1DM, celiac disease, multiple sclerosis, and/or rheumatoid arthritis, respectively. However, a possible association with rosacea was not investigated. OBJECTIVE: We evaluated the association between rosacea and T1DM, celiac disease, multiple sclerosis, and rheumatoid arthritis, respectively. METHODS: We performed a population-based case-control study. A total of 6759 patients with rosacea were identified and matched with 33,795 control subjects on age, sex, and calendar time. We used conditional logistic regression to calculate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: After adjustment for smoking and socioeconomic status, patients with rosacea had significantly increased ORs for T1DM (OR 2.59, 95% CI 1.41-4.73), celiac disease (OR 2.03, 95% CI 1.35-3.07), multiple sclerosis (OR 1.65, 95% CI 1.20-2.28), and rheumatoid arthritis (OR 2.14, 95% CI 1.82-2.52). The association was mainly observed in women. LIMITATIONS: We were unable to distinguish between the different subtypes and severities of rosacea. CONCLUSIONS: Rosacea is associated with T1DM, celiac disease, multiple sclerosis, and rheumatoid arthritis, respectively, in women, whereas the association in men only reached statistical significance for rheumatoid arthritis. PMID- 26830865 TI - High azathioprine dose and lip cancer risk in liver, heart, and lung transplant recipients: A population-based cohort study. AB - BACKGROUND: Iatrogenic immunosuppression is a risk factor for lip cancer but the determinants are unknown. OBJECTIVE: We sought to quantify the association between the type, dose, and duration of iatrogenic immunosuppression and lip cancer risk in solid organ transplant recipients. METHODS: We conducted a population-based cohort study of all adult Australian liver, heart, and lung transplant recipients from 1984 to 2006 (n = 4141). We abstracted longitudinal data from medical records and ascertained incident lip cancer (n = 58) and deaths (n = 1434) by linkage with national registries. We estimated multivariable hazard ratios (HR) for lip cancer using the Fine and Gray proportional subdistribution hazards model, accounting for death as a competing risk. RESULTS: Lip cancer risk (n = 58) increased with high mean daily dose of azathioprine (HR 2.28, 95% confidence interval [CI] 1.18-4.38), longer duration of immunosuppression (HR 9.86, 95% CI 2.10-46.3), increasing year of age at transplantation (HR 1.14, 95% CI 1.04-1.25), earlier transplantation era (HR 8.73, 95% CI 1.11-68.7), and history of smoking (HR 2.71, 95% CI 1.09-6.70). LIMITATIONS: Data on potential confounders such as personal solar ultraviolet radiation exposure were not available. CONCLUSION: Higher doses of azathioprine increase lip cancer risk, with implications for managing immunosuppressed populations and our understanding of the relationship between solar ultraviolet radiation and lip cancer. PMID- 26830866 TI - Diagnostic criteria for and clinical review of melanonychia in Korean patients. AB - BACKGROUND: Melanonychia may be the presenting sign of ungual melanoma. However, there are insufficient basic clinical data for melanonychia in Korean patients. OBJECTIVE: We sought to identify basic clinical data and devise a classification algorithm for melanonychia. METHODS: In all, 275 patients with melanonychia who visited our clinic from January 2002 to August 2014 were included in this study. We reviewed medical records, clinical and dermoscopic photographs, and histopathologic findings and we assessed demographics (eg, age); medical (eg, systemic diseases), family, and trauma (eg, nail biting) history; and physical findings (eg, affected number and site). RESULTS: The 5 most common causes of melanonychia in Korean patients were subungual hemorrhage (29.1%), nail matrix nevus (21.8%), trauma-induced pigmentation (14.5%), nail apparatus lentigo (11.6%), and ethnic-type nail pigmentation (8.0%). Melanoma was diagnosed in 6.2% of patients. Ethnic-type nail pigmentation was commonly identified. LIMITATIONS: This is a retrospective study from a single center. CONCLUSION: We propose a revised diagnostic algorithm for melanonychia to assist in the evaluation of this condition. PMID- 26830867 TI - Follicular vitiligo: A report of 8 cases. AB - BACKGROUND: Follicular vitiligo, a recently proposed new subtype of vitiligo, has primary involvement of the hair follicle melanocytic reservoir. OBJECTIVE: We sought to characterize follicular vitiligo through a case series of 8 patients. METHODS: Patients with features of follicular vitiligo who were seen at the vitiligo clinic in the National Center for Rare Skin Disorders in Bordeaux, France, were recruited. A retrospective review of case records and clinical photographs was carried out. RESULTS: There were 8 male patients with a mean age of 48 years. All patients reported significant whitening of their body and, in some, scalp hairs before cutaneous depigmentation. Examination revealed classic generalized depigmented lesions of vitiligo and an impressive presence of leukotrichia, not only in the vitiliginous areas, but also in areas with clinically normal-appearing skin. Punch biopsy specimen of the leukotrichia and vitiligo lesions demonstrated loss of melanocytes and precursors in the basal epidermis and hair follicle. LIMITATIONS: This was a cross-sectional study based on a single-center experience. CONCLUSION: Follicular vitiligo is a distinct entity within the spectrum of vitiligo. This entity may serve as the missing link between alopecia areata and vitiligo, with probable physiopathological similarities between these conditions. PMID- 26830870 TI - Three-Day-Old Boy With Palmar Pustules. PMID- 26830871 TI - Supporting Child Play. PMID- 26830873 TI - Children Exposed to Abuse in Youth-Serving Organizations: Results From National Sample Surveys. AB - IMPORTANCE: Protecting children in youth-serving organizations is a national concern. OBJECTIVE: To provide clinicians, policymakers, and parents with estimates of children's exposure to abuse in youth-serving organizations. DESIGN, SETTING, AND PARTICIPANTS: Telephone survey data from the 3 National Surveys of Children's Exposure to Violence (2008, 2011, and 2014) were combined to create a sample of 13,052 children and youths aged 0 to 17 years. The survey participants included youths aged 10 to 17 years and caregivers of children aged 0 to 9 years. MAIN OUTCOMES AND MEASURES: Items from the Juvenile Victimization Questionnaire. RESULTS: In the combined sample of 13 052 children and youths aged 0 to 17 years, the rate of abuse by persons in youth-serving organizations was 0.4% (95% CI, 0.2 0.7) for the past year and 0.8% (95% CI, 0.5-1.1) over the lifetime. Most of the maltreatment (63.2%) was verbal abuse and only 6.4% was any form of sexual violence or assault. CONCLUSIONS AND RELEVANCE: Abuse in youth-serving organizations was a relatively rare form of abuse, dwarfed by abuse by family members and other adults. PMID- 26830874 TI - Optimization of the management of platelet concentrate stocks in the Basque Country using mathematical simulation. AB - BACKGROUND AND OBJECTIVES: The management of platelet concentrate (PC) stocks is not simple given their short shelf life and variable demand. In general, managers decide on PC production based on personal experience. The objective of this study was to provide a tool to help decide how many PC units to produce each day in a more rational and objective way. MATERIALS AND METHODS: From the historical data on PCs produced, transfused and discarded in the Basque Country in 2012, a mathematical model was built, based on the normality of the time series of the transfusions performed on each day of the week throughout the year. This model was implemented in an easy-to-use Excel spreadsheet and validated using real production data from 2013. RESULTS: Comparing with real 2013 data, in the best scenario, the number of PC units that expired was 87.7% lower, PC production, 14.3% lower and the age of the PCs transfused nearly 1-day younger in the simulation. If we want to ensure a minimum stock at the end of each day, the outdating rate and average age of the transfused PCs progressively increase. CONCLUSION: The practical application of the designed tool can facilitate decision-making about how many PC units to produce each day, resulting in very significant reductions in PC production and wastage and corresponding cost savings, together with an almost 1 day decrease in the mean age of PCs transfused. PMID- 26830872 TI - Polygenic Risk, Appetite Traits, and Weight Gain in Middle Childhood: A Longitudinal Study. AB - IMPORTANCE: Genome-wide association studies have identified genetic risks for obesity. These genetic risks influence development of obesity partly by accelerating weight gain in childhood. Research is needed to identify mechanisms to inform intervention. Cross-sectional studies suggest appetite traits as a candidate mechanism. Longitudinal studies are needed to test whether appetite traits mediate genetic influences on children's weight gain. OBJECTIVE: To test whether genetic risk for obesity predicts accelerated weight gain in middle childhood (ages 4-8 years) and whether genetic association with accelerated weight gain is mediated by appetite traits. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal study of a representative birth cohort at the Trondheim Early Secure Study, Trondheim, Norway, enrolled at age 4 years during 2007 to 2008, with follow-ups at ages 6 and 8 years. Participants were sampled from all children born in 2003 or 2004 who attended regular community health checkups for 4-year olds (97.2% attendance; 82.0% consent rate, n = 2475). Nine hundred ninety-five children participated at age 4 years, 795 at age 6 years, and 699 at age 8 years. Analyses included 652 children with genotype, adiposity, and appetite data. MAIN OUTCOMES AND MEASURES: Outcomes were body mass index and body-fat phenotypes measured from anthropometry (ages 4, 6, and 8 years) and bioelectrical impedance (ages 6 and 8 years). Genetic risk for obesity was measured using a genetic risk score composed of 32 single-nucleotide polymorphisms previously discovered in genome-wide association studies of adult body mass index. Appetite traits were measured at age 6 years with the Children's Eating Behavior Questionnaire. RESULTS: Of the 652 genotyped child participants, 323 (49.5%) were female, 58 (8.9%) were overweight, and 1 (0.2%) was obese. Children at higher genetic risk for obesity had higher baseline body mass index and fat mass compared with lower genetic risk peers, and they gained weight and fat mass more rapidly during follow-up. Each SD increase in genetic risk score was associated with a 0.22 point increase in BMI at age-4 baseline (for the intercept, unstandardized path coefficient B = 0.22 [95% CI, 0.06-0.38]; P = .008. Children with higher genetic risk scores also gained BMI points more rapidly from ages 4 to 6 years (B = 0.11 [95% CI, 0.03-0.20]; P = .01 ; beta = 0.12) and from 6 to 8 years (B = 0.09 [95% CI, 0.00-0.19]; P = .05; beta = 0.10), compared with their lower genetic risk peers. Children at higher genetic risk had higher levels of alleged obesogenic appetite traits than peers with lower genetic risk at age 6 years, but appetite traits did not mediate genetic associations with weight gain. The sum of the 5 indirect effects was B = -0.001 (95% CI, -0.02 -0.01); P = .86; beta = 0.00. CONCLUSIONS AND RELEVANCE: Genetic risk for obesity is associated with accelerated childhood weight gain. Interventions targeting childhood weight gain may provide one path to mitigating genetic risk. However, middle childhood appetite traits may not be a promising target for such interventions. Studies of early-childhood samples are needed to test whether appetite traits explain how genetic risks accelerate growth earlier in development. PMID- 26830875 TI - Research and Evaluations of the Health Aspects of Disasters, Part VI: Interventional Research and the Disaster Logic Model. AB - Disaster-related interventions are actions or responses undertaken during any phase of a disaster to change the current status of an affected community or a Societal System. Interventional disaster research aims to evaluate the results of such interventions in order to develop standards and best practices in Disaster Health that can be applied to disaster risk reduction. Considering interventions as production functions (transformation processes) structures the analyses and cataloguing of interventions/responses that are implemented prior to, during, or following a disaster or other emergency. Since currently it is not possible to do randomized, controlled studies of disasters, in order to validate the derived standards and best practices, the results of the studies must be compared and synthesized with results from other studies (ie, systematic reviews). Such reviews will be facilitated by the selected studies being structured using accepted frameworks. A logic model is a graphic representation of the transformation processes of a program [project] that shows the intended relationships between investments and results. Logic models are used to describe a program and its theory of change, and they provide a method for the analyzing and evaluating interventions. The Disaster Logic Model (DLM) is an adaptation of a logic model used for the evaluation of educational programs and provides the structure required for the analysis of disaster-related interventions. It incorporates a(n): definition of the current functional status of a community or Societal System, identification of needs, definition of goals, selection of objectives, implementation of the intervention(s), and evaluation of the effects, outcomes, costs, and impacts of the interventions. It is useful for determining the value of an intervention and it also provides the structure for analyzing the processes used in providing the intervention according to the Relief/Recovery and Risk-Reduction Frameworks. PMID- 26830876 TI - Atypical presentation of painful vesicles on the hands and feet in an immunocompromised adult. PMID- 26830877 TI - Actin Dynamics Regulates Dendritic Cell-Mediated Transfer of HIV-1 to T Cells. AB - Whereas human dendritic cells (DCs) are largely resistant to productive infection with HIV-1, they have a unique ability to take up the virus and transmit it efficiently to T lymphocytes through a process of trans-infection or trans enhancement. To elucidate the molecular and cell biological mechanism for trans enhancement, we performed an shRNA screen of several hundred genes involved in organelle and membrane trafficking in immature human monocyte-derived dendritic cells (MDDCs). We identified TSPAN7 and DNM2, which control actin nucleation and stabilization, as having important and distinct roles in limiting HIV-1 endocytosis and in maintaining virus particles on dendrites, which is required for efficient transfer to T lymphocytes. Further characterization of this process may provide insights not only into the role of DCs in transmission and dissemination of HIV-1 but also more broadly into mechanisms controlling capture and internalization of pathogens. PMID- 26830878 TI - Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors. AB - The Notch protein is one of the most mechanistically direct transmembrane receptors-the intracellular domain contains a transcriptional regulator that is released from the membrane when engagement of the cognate extracellular ligand induces intramembrane proteolysis. We find that chimeric forms of Notch, in which both the extracellular sensor module and the intracellular transcriptional module are replaced with heterologous protein domains, can serve as a general platform for generating novel cell-cell contact signaling pathways. Synthetic Notch (synNotch) pathways can drive user-defined functional responses in diverse mammalian cell types. Because individual synNotch pathways do not share common signaling intermediates, the pathways are functionally orthogonal. Thus, multiple synNotch receptors can be used in the same cell to achieve combinatorial integration of environmental cues, including Boolean response programs, multi cellular signaling cascades, and self-organized cellular patterns. SynNotch receptors provide extraordinary flexibility in engineering cells with customized sensing/response behaviors to user-specified extracellular cues. PMID- 26830880 TI - Stochastic detection and characterisation of individual ferrocene derivative tagged graphene nanoplatelets. AB - Graphene nanoplatelets (GNPs) are 'tagged' with 1-(biphen-4-yl)ferrocene. Chronoamperometry is then utilised to observe single particle impacts when GNPs suspended in solution collide with a carbon fibre micro wire electrode held at an oxidising potential, resulting in current/time transient "spikes". The impacts are associated with two types of charge transfer: Faradaic due to oxidation of the 'tag' and capacitative due to disruption of the double layer. Analysis of the spikes suggests approximate monolayer coverage of 1-(biphen-4-yl)ferrocene on the GNP surfaces, with a surface coverage of (2.2 +/- 0.3) * 10(-10) mol cm(-2). In contrast non-derivatised ferrocene does not exhibit any significant adsorption on the GNP material. PMID- 26830879 TI - Precision Tumor Recognition by T Cells With Combinatorial Antigen-Sensing Circuits. AB - T cells can be re-directed to kill cancer cells using chimeric antigen receptors (CARs) or T cell receptors (TCRs). This approach, however, is constrained by the rarity of tumor-specific single antigens. Targeting antigens also found on bystander tissues can cause life-threatening adverse effects. A powerful way to enhance ON-target activity of therapeutic T cells is to engineer them to require combinatorial antigens. Here, we engineer a combinatorially activated T cell circuit in which a synthetic Notch receptor for one antigen induces the expression of a CAR for a second antigen. These dual-receptor AND-gate T cells are only armed and activated in the presence of dual antigen tumor cells. These T cells show precise therapeutic discrimination in vivo-sparing single antigen "bystander" tumors while efficiently clearing combinatorial antigen "disease" tumors. This type of precision dual-receptor circuit opens the door to immune recognition of a wider range of tumors. VIDEO ABSTRACT. PMID- 26830881 TI - Long-Term Pharmacological Treatments of Anxiety Disorders: An Updated Systematic Review. AB - Many aspects of long-term pharmacological treatments for anxiety disorders (AnxDs) are still debated. We undertook an updated systematic review of long-term pharmacological studies on panic disorder (PD), generalized anxiety disorder (GAD), and social anxiety disorder (SAD). Relevant studies dating from January 1, 2012 to August 31, 2015 were identified using the PubMed database and a review of bibliographies. Of 372 records identified in the search, five studies on PD and 15 on GAD were included in the review. No studies on SAD were found. Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy. Paroxetine, escitalopram, and clonazepam can be effective for long-term treatment of PD. However, further studies are needed to draw conclusions about the long-term benzodiazepine use in PD, particularly for the possible cognitive side-effects over time. Pregabalin and quetiapine can be effective for long-term treatment of GAD, while preliminary suggestions emerged for agomelatine and vortioxetine. We did not find any evidence for determining the optimal length and/or dosage of medications to minimize the relapse risk. Few investigations have attempted to identify potential predictors of long-term treatment response. Personalized treatments for AnxDs can be implemented using predictive tools to explore those factors affecting treatment response/tolerability heterogeneity, including neurobiological functions/clinical profiles, comorbidity, biomarkers, and genetic features, and to tailor medications according to each patient's unique features. PMID- 26830882 TI - Maternal Affective Illness in the Perinatal Period and Child Development: Findings on Developmental Timing, Mechanisms, and Intervention. AB - Maternal mental illness is one of the most reliable risks for clinically significant child adjustment difficulties. The research literature in this area is very large and broad and dates back decades. In this review, we consider recent research findings on maternal mental illness and child development by focusing particularly on affective illness the perinatal period. We do this because maternal affective illness in the perinatal period is common; recent evidence suggests that pre- and postpartum maternal depression may have lasting effects on child behavioral and somatic health; research in the perinatal period raises acute and compelling questions about mechanisms of transmission and effect; and perinatal-focused interventions may offer distinct advantages for benefitting mother and child and gaining insights into developmental mechanisms. Throughout the review, we attend to the increasing integration of psychological and biological models and the trans-disciplinary approach now required for clinical investigation. PMID- 26830884 TI - The Importance of Military Cultural Competence. AB - Military cultural competence has recently gained national attention. Experts have posited that limited outcomes in the treatment of posttraumatic stress disorder and depression in the military may be related to limited familiarity with the military. National surveys have indicated low military cultural competence among providers and limited educational efforts on military culture or pertinent military pathology in medical schools and residency training programs. Military families, with their own unique military cultural identity, have been identified as a population with increased risks associated with deployment. In response to these findings, several curricula regarding military culture have been established and widely distributed. Assessments of military cultural competence have also been developed. The clinical impact of enhanced cultural competence in general has thus far been limited. The military, however, with its highly prescribed cultural identity, may be a model culture for further study. PMID- 26830883 TI - New Developments in Cognitive-Behavioral Therapy for Social Anxiety Disorder. AB - Social anxiety disorder (SAD) is a highly prevalent and chronic disorder that causes considerable psychosocial impairment. This article reviews recent changes in the definition of SAD in DSM-5 and summarizes the current evidence for effective cognitive-behavioral treatments in adults, children, and adolescents. Current data suggests that cognitive-behavioral therapy (CBT) is efficacious in the treatment of this condition. Among different CBT approaches, individual cognitive therapy may be associated with the largest effect sizes. In this review, interventions targeting dysfunctional cognitive processes that contribute to the effective treatment of SAD are discussed. Some recent findings from neuroimaging research and studies on the augmentation of CBT using neuroenhancers indicate that changes in emotion regulation as well as fear extinction are important psychological mediators of positive outcome. Furthermore, internet delivered CBT is a promising field of technological innovation that may improve access to effective treatments. Despite the availability of effective treatments, treatment-resistant SAD remains a common problem in clinical practice that requires more research efforts. Finally, potential areas for further development of CBT as well as its dissemination in health care are summarized. PMID- 26830885 TI - The Prevalence and Diagnostic Validity of Short-Duration Hypomanic Episodes and Major Depressive Episodes. AB - Current diagnostic criteria for a hypomanic episode, as outlined in both the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV and DSM-5), require a minimum duration of four consecutive days of symptoms of mood elevation. The 4-day criterion for duration of hypomania has been challenged as arbitrary and lacking empirical support, with many arguing that shorter-duration hypomanic episodes are highly prevalent and that those experiencing these episodes are clinically more similar to patients with bipolar disorder than to those with unipolar major depressive disorder. We review the current evidence regarding the prevalence, diagnostic validity, and longitudinal illness correlates of shorter-duration hypomanic episodes and summarize the arguments for and against broadening the diagnostic criteria for hypomania to include shorter-duration variants. Accumulating findings suggest that patients with major depressive episodes and shorter-duration hypomanic episodes represent a complex clinical phenotype, perhaps best conceptualized as being on the continuum between those with unipolar depressive episodes alone and those with DSM-5-defined bipolar II disorder. Further investigation is warranted, ideally involving large prospective, controlled studies, to elucidate the diagnostic and treatment implications of depression with shorter-duration hypomanic episodes. PMID- 26830886 TI - Sexual Function Across Aging. AB - Women experience multiple changes in social and reproductive statuses across the life span which can affect sexual functioning. Various phases of the sexual response cycle may be impacted and can lead to sexual dysfunction. Screening for sexual problems and consideration of contributing factors such as neurobiology, reproductive life events, medical problems, medication use, and depression can help guide appropriate treatment and thereby improve the sexual functioning and quality of life of affected women. Treatment options include psychotropic medications, hormone therapy, and psychotherapy. PMID- 26830888 TI - Can resuscitation run like a fine Swiss timepiece? PMID- 26830887 TI - Avoidant Personality Disorder: a Current Review. AB - This review focuses on recent research on diagnostic aspects, etiology, and treatment of avoidant personality disorder (AVPD). Current studies stress the close relation between AVPD and social anxiety disorder, the influence of genetic factors in the development of AVPD, and the relative stability of symptoms. Treatment approaches should target the pervasive patterns of social inhibition, feelings of inadequacy, and hypersensitivity to negative evaluation. Empirical evidence for cognitive-behavior and schema therapy is promising. Few other therapeutic approaches have been developed, but until now, these have only been investigated in case studies. We conclude that AVPD qualifies as a neglected disorder and that more research specifically on avoidant personality disorder symptoms and its treatment is needed. PMID- 26830889 TI - Multiple leadless pacemakers implanted in the right ventricle of swine. AB - AIMS: The miniaturized leadless pacemaker has recently emerged as a bradycardia therapy in humans, and many patients may need at least two pacemakers in their lifetime. Thus, the present study assessed the effect of two leadless pacemakers in the right ventricle (RV) on cardiac function in a swine model. METHODS AND RESULTS: Fourteen mini pigs were chronically studied. Each animal received two sequential leadless pacemakers in the RV with 1 month between two separate implantations. All animals were then followed for 6 months. Cardiac function was assessed with echocardiography at baseline, the second implantation, and the end of the 6-month follow-up. A necropsy at the end of the study was performed to measure the length of the fibrous tissue covering the devices and assess tricuspid valve integrity. Four animals died during the surgical procedure, and one animal died of infection during the follow-up period. In the remaining nine animals, there were no significant changes in left ventricular ejection fraction, aortic time integral, cardiac output, and left ventricular size from baseline to the end of the study. The mean length of fibrous tissue covering Micra devices was 14.3 +/- 7.8 mm. No tricuspid valve injury was observed. CONCLUSION: Multiple leadless pacemakers implanted in the RV do not appear to impact cardiac function. Therefore, it appears safe to implant multiple leadless pacemakers in the same heart. PMID- 26830890 TI - Significance and mechanisms of the electrocardiographic pattern of early repolarization. PMID- 26830891 TI - Real-world persistence and adherence to oral anticoagulation for stroke risk reduction in patients with atrial fibrillation. AB - AIM: To assess persistence and adherence to rivaroxaban, dabigatran, and vitamin K antagonist (VKA) treatment in primary care patients with non-valvular atrial fibrillation (AF) newly starting anticoagulant therapy. METHODS AND RESULTS: Prescription data for oral anticoagulants were obtained from 7265 eligible patients from primary care practices across Germany. Persistence with and adherence to anticoagulation were assessed in anticoagulant-naive patients with AF newly treated with dabigatran, rivaroxaban, or VKA during follow-up periods of at least 180 days, respectively 360 days after the prescription date. Persistence probabilities after 180 days were 66.0% for rivaroxaban, 60.3% for dabigatran, and 58.1% for VKA (P < 0.001 for rivaroxaban vs. VKA and P = 0.008 for rivaroxaban vs. dabigatran). After 360 days, persistence probabilities were 53.1, 47.3, and 25.5%, respectively (P < 0.001 for rivaroxaban and dabigatran vs. VKA). Considering the development over 360 days rivaroxaban demonstrated a better persistence compared with dabigatran (P = 0.026). Male gender and the presence of diabetes mellitus were associated with increased persistence, while renal impairment and antiplatelet drug use decreased persistence. High adherence (MPR >=0.80) was observed in 61.4% of rivaroxaban users and in 49.5% of dabigatran users, with means of 0.76 [95% confidence interval (CI) 0.74-0.78] for rivaroxaban and 0.67 (95% CI 0.65-0.69) for dabigatran (P < 0.001). CONCLUSIONS: Rivaroxaban and dabigatran demonstrated better persistence than VKA at Day 360. Furthermore, rivaroxaban was associated with better persistence and adherence than dabigatran. Further studies are needed to identify factors responsible for this difference and evaluate the impact on outcomes. PMID- 26830892 TI - P2X7R large pore is partially blocked by pore forming proteins antagonists in astrocytes. AB - The ATP-gated P2X7R (P2X7R) is a channel, which is involved in events, such as inflammation, cell death, and pain. The most intriguing event concerning P2X7R functions is the phenomenon of pore dilation. Once P2X7R is activated, the permeability of the plasma membrane becomes higher, leading to the permeation of 1000 Da-weight solutes. The mechanisms involved in this process remain unclear. Nevertheless, this event is not exclusively through P2X7R, as other proteins may form large pores in the plasma membrane. Recent evidence concerning pore formation reveals putative P2X7R and other pores-associated protein complexes, revealing cross-interactive pharmacological and biophysical issues. In this work, we showed results that corroborated with cross-interactive aspects with P2X7R and pores in astrocytes. These cells expressed most of the pores, including P2X7R. We discovered that different pore types open with peculiar characteristics, as both anionic and cationic charged solutes permeate the plasma membrane, following P2X7R activation. Moreover, we showed that both synergic and additive relationships are found within P2X7, cationic, and anionic large pores. Therefore, our data suggest that other protein-related pores are assembled following the formation of P2X7R pore. PMID- 26830893 TI - Prevention of Depression in At-Risk Adolescents: Moderators of Long-term Response. AB - In a randomized controlled trial, we found that a cognitive behavioral program (CBP) was significantly more effective than usual care (UC) in preventing the onset of depressive episodes, although not everyone benefitted from the CBP intervention. The present paper explored this heterogeneity of response. Participants were 316 adolescents (M age = 14.8, SD = 1.4) at risk for depression due to having had a prior depressive episode or having current subsyndromal depressive symptoms and having a parent with a history of depression. Using a recursive partitioning approach to baseline characteristics, we (Weersing et al. 2016) previously had identified distinct risk clusters within conditions that predicted depressive episodes through the end of the continuation phase (month 9). The present study used the same risk clusters that had been derived in the CBP group through month 9 to reclassify the UC group and then to examine group differences in depression through month 33. We found that in this overall very high-risk sample, the CBP program was superior to UC among youth in the low-risk cluster (n = 33), characterized by higher functioning, lower anxiety, and parents not depressed at baseline, but not in the middle (n = 95) and high-risk (n = 25) clusters. Across conditions, significantly more depression-free days were found for youth in the low-risk cluster (M = 951.9, SD = 138.8) as compared to youth in the high-risk cluster (M = 800.5, SD = 226.7). Identification of moderators, based on purely prognostic indices, allows for more efficient use of resources and suggests possible prevention targets so as to increase the power of the intervention. PMID- 26830895 TI - [La penurie de serums antivenimeux]. PMID- 26830896 TI - [Identification of anopheles breeding sites in the residual foci of low malaria transmission "hotspots" in Central and Western Senegal]. AB - Malaria incidence has markedly declined in the Mbour, Fatick, Niakhar and Bambey districts (central and western Senegal) thanks to a scaling up of effective control measures namely LLINs (Long Lasting Insecticide Treated Net), ACTs (Artesunate Combination Therapy) and promoting care seeking. However malaria cases are now maintained by foci of transmission called hotspots. We evaluate the role of anopheles breeding sites in the identification of malaria hotspots in the health districts of Mbour, Fatick, Niakhar and Bambey. Surveys of breeding sites were made in 6 hotspot villages and 4 non-hotspot villages. A sample was taken in each water point with mosquito larvae by dipping method and the collected specimens were identified to the genus level. Additional parameters as name of the village and breeding sites, type of collection, original water turbidity, presence of vegetation, proximity to dwellings, geographic coordinates, sizes were also collected. Sixty-two water collections were surveyed and monitored between 2013 and 2014. Temporary natural breeding sites were predominant regardless of the epidemiological status of the village. Among the 31 breeding sites located within 500 meters of dwellings in hotspots villages, 70% carried Anopheles larvae during the rainy season while 43% of the 21 breeding sites located at similar distances in non-hotspot villages carried Anopheles larvae during the same period (P = 0.042). At the end of the rainy season, the trend is the same with 27% of positive breeding sites in hotspots and 14% in non-hotspots villages. The breeding sites encountered in hotspots villages are mostly small to medium size and are more productive by Anopheles larvae than those found in non hotspot area. This study showed that the high frequency of smallest and productive breeding sites around and inside the villages can create conditions of residual transmission. PMID- 26830898 TI - Residential mobility and the risk of childhood leukemia. AB - PURPOSE: An infective origin of childhood leukemia has been postulated, with leukemia developing as a rare response to an infection. Population mixing can result in increased contacts between infected and susceptible individuals and may increase the risk of leukemia. The objective of this study was to investigate the association between residential mobility as an indicator of population mixing at individual level and the risk of leukemia in children (<15 years). METHODS: We conducted a population-based case-control study using Finnish register data. Cases (n = 1,093) were all children diagnosed with leukemia (M9800-M9948 in ICD-O 3) at <15 years of age in Finland in 1990-2011. We chose randomly three controls per case (n = 3,279), free of cancer and alive in the end of the index year (diagnosis of the case). Controls were matched by sex and age. A comprehensive history of residential mobility was constructed from the population registry including overall migration, moving to a larger municipality (more inhabitants), and moving to a municipality with low, intermediate, or high migration intensity. The association between residential mobility and the risk of childhood leukemia was evaluated using conditional logistic regression. RESULTS: We did not observe consistently increased or decreased risks of childhood leukemia associated with different migration patterns. Overall, residential mobility showed odds ratios nonsignificantly below unity, and no elevated risks were found. CONCLUSION: Our results do not indicate that higher residential mobility or moving to municipalities with more inhabitants is associated with risk of childhood leukemia. PMID- 26830897 TI - [Non-heart-beating donors are ineligible]. AB - The death of the donor is a mandatory prerequisite for organ transplantation (dead donor rule) worldwide. It is a medical, legal and ethical consensus to accept the concept of brain death, as first proposed in 1968 by the ad hoc committee of the Harvard Medical School, as a certain criterion of death. In isolated cases where the diagnosis of brain death was claimed to be wrong, it could be demonstrated that the diagnostic procedure for brain death had not been correctly performed. In March 2014 a joint statement by the German neuromedical societies emphasized that 1) the diagnosis of brain death is one of the safest diagnoses in medicine if performed according to accepted medical standards and criteria and 2) the concept of non-heart-beating donors (NHBD, i. e. organ donation after an arbitrarily defined duration of circulatory and cardiac arrest) practiced in some European countries must be absolutely rejected because it implicates a high risk of diagnostic error. According to the current literature it is unclear at what time cardiac and circulatory arrest is irreversible and leads to irreversible cessation of all functions of the entire brain including the brainstem, even though clinical signs of cessation of brain functions are always found after 10 min. Furthermore, is it often an arbitrary decision to exactly define the duration of cardiac arrest if continuous echocardiographic monitoring has not been carried out from the very beginning. Last but not least there are ethical concerns against the concept of NHBD because it might influence therapeutic efforts to resuscitate a patient with cardiac arrest. Therefore, the German Medical Council (BAK) has repeatedly rejected the concept of NHBD for organ transplantation since 1995. PMID- 26830899 TI - Dietary total antioxidant capacity in relation to endometrial cancer risk: a case control study in Italy. AB - PURPOSE: To investigate the role of the overall antioxidant activity of diet, we estimated the relation between three dietary indices of total antioxidant capacity (TAC) and endometrial cancer risk METHODS: We analyzed data from an Italian case-control study including 454 women with incident, histologically confirmed endometrial cancer, and 908 frequency-matched controls admitted to the same hospitals as cases for acute non-neoplastic conditions. A reproducible and valid food frequency questionnaire was used to assess subjects' habitual diet. TAC was measured using Italian food composition tables in terms of Ferric reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC), and total radical-trapping antioxidant parameter (TRAP). We computed odds ratios (OR) and corresponding 95 % confidence intervals (CIs) using conditional multiple logistic regression models, including terms for recognized endometrial cancer risk factors and total energy intake. RESULTS: TAC was inversely related to endometrial cancer risk with ORs for the highest versus the lowest quartile of 0.69 (95 % CI 0.47-1.00) for FRAP, 0.68 (95 % CI 0.46-0.99) for TEAC, and 0.68 (95 % CI 0.47-0.98) for TRAP. The relations appeared consistent in strata of selected risk factors and decreased when considering TAC without the contribution of coffee. CONCLUSIONS: Our findings suggest a favorable role of a diet high in TAC on endometrial cancer risk, which can be partially driven by coffee consumption. PMID- 26830900 TI - Racial disparities in endometrial cancer mortality-to-incidence ratios among Blacks and Whites in South Carolina. AB - PURPOSE: Endometrial cancer (EC) exhibits striking racial disparities with higher mortality in Blacks compared to Whites. The mortality-to-incidence ratio (MIR) provides a population-based measure of survival which accounts for incidence. The objective of this study was to map EC MIRs by race for eight health regions within South Carolina (SC) and chart EC incidence by race and grade across the four cancer stages. METHODS: Cancer incidence and mortality data were obtained from the SC Community Access Network (SCAN), the online data query system provided by the SC Department of Health and Environmental Control (DHEC). The underlying data for SCAN were generated from the SC Central Cancer Registry and SC DHEC Vital Records and used to construct MIRs. ArcGIS 10.1 was used to map EC MIRs by race for eight health regions within SC. Four categories of MIR were derived using the national MIR for EC among Whites as the reference category. RESULTS: Blacks had higher levels of poorly differentiated tumors across all stages and higher incidence and mortality rates. In all eight health regions, Blacks were in the highest MIR category. By contrast, the MIRs for Whites were more evenly represented over the four categories. CONCLUSIONS: The MIR proved useful for identifying disparities in EC incidence and mortality among Black and White women in SC. Cancer surveillance programs may use the MIR to monitor disparities across racial/ethnic groups and geographic regions going forward. MIRs have the potential to serve as an indicator of the long-term success of cancer surveillance programs. PMID- 26830901 TI - Alcohol intake from early adulthood to midlife and mammographic density. AB - PURPOSE: Moderate alcohol consumption (15 g/day) has been consistently associated with increased breast cancer risk; however, the association between alcohol and mammographic density, a strong marker of breast cancer risk, has been less consistent. Less is known about the effect of patterns of alcohol intake across the lifecourse. METHODS: Using the Early Determinants of Mammographic Density study, an adult follow-up of women born in two US birth cohorts (n = 697; Collaborative Perinatal Project in Boston and Providence sites and the Childhood Health and Development Studies in California), we examined the association between alcohol intake in early adulthood (ages 20-29 years) and at time of interview and mammographic density (percent density and total dense area). We report the difference between nondrinkers and three levels of alcohol intake. We considered confounding by age at mammogram, body mass index, geographic site, race/ethnicity, and reproductive characteristics. RESULTS: Seventy-nine percent of women reported ever consuming alcohol. Compared to nondrinkers in early adulthood, we observed an inverse association between >7 servings/week and percent density in fully adjusted models (beta = -5.1, 95% CI -8.7, -1.5; p for trend = <0.01). Associations with dense area were inverse for the highest category of drinking in early adulthood but not statistically significant (p for trend = 0.15). Compared to noncurrent drinkers, the association for current intake of >7 servings/week and percent density was also inverse (beta = -3.1, 95% CI -7.0, 0.8; p for trend = 0.01). In contrast, moderate alcohol intake (>0-<=7 servings/week) in either time period was positively associated with dense area; but associations were not statistically significant in fully adjusted models. CONCLUSIONS: Our study does not lend support to the hypothesis that the positive association between alcohol intake and breast cancer risk is through increasing mammographic density. PMID- 26830902 TI - A case of tubulocystic carcinoma of the kidney with aggressive features. AB - Tubulocystic carcinoma of the kidney is rare and typically indolent. Our case involved an aggressive tubulocystic carcinoma as well as the radiological confirmation of its relation to papillary renal cell carcinoma. A 46-year-old male presented with renal multiloculated cysts with a solid part. On computed tomography and magnetic resonance imaging, the solid part showed the characteristics of papillary renal cell carcinoma. Contrast enhancement of the solid part was fluffy and sparse because of the coexistence of cysts. Perirenal fat invasion resulted in exophytic cysts, and renal-hilar cystic lymph node metastasis existed. The histopathological diagnosis was tubulocystic carcinoma associated with areas of papillary renal cell carcinoma and poorly differentiated carcinoma with metastasis. Our case suggests that the solid part enhancement of tubulocystic carcinoma tends to be fluffy and sparse, and exophytic cysts and cystic lymph nodes may show radiologically aggressive findings. PMID- 26830903 TI - The high incidence of anti-Ro/SSA and anti-p200 antibodies in female patients with connective tissue diseases confirms the importance of screening for congenital heart block-associated autoantibodies during pregnancy. AB - It is known that anti-Ro/SSA positivity leads to higher risk of miscarriage and fetal cardiac malformations. Particularly, anti-p200 antibodies against a finer specificity of the Ro/SSA antigen, have been associated with congenital heart block. The aim of the study was to assess the frequency of anti-p200 among female patients with different connective tissue diseases and, among these, the relevance of anti-p200 values in patients with cutaneous diseases compared to systemic diseases. Anti-p200 were investigated in 110 anti-Ro/SSA positive female sera, sent to our laboratory between 2008 and 2014 with suspect of connective disease, by using ELISA testing. Positivity was found in 40.9 % samples, 34 of them showed a strong positivity (values >= 1.0, cut off = 0.7). Patients with systemic diseases were anti-p200 positive in the 45.9 % of cases while patients with cutaneous diseases were positive in the 24.0 % of cases. Positivity for anti p200 antibodies was revealed in 24.0 % of patients with discoid lupus erythematosus; 100 % of patients with dermatomyositis; 40.0 % of patients with mixed connective tissue disease; 25.0 % of patients with rheumatoid arthritis; 100 % of patients with Sjogren's syndrome; 33.3 % of patients with subacute cutaneous lupus erythematosus; 42.9 % of patients with systemic lupus erythematosus; 80.0 % of patients with systemic sclerosis. No significant difference in anti-p200 prevalence was found between systemic and cutaneous involvement, nevertheless, considering only positive sera, the antibody titer was higher in systemic diseases rather than in cutaneous diseases (2.6 +/- 1.7 and 1.7 +/- 1.9; p = 0.041). The authors think screenings for anti-Ro/SSA and anti p200 antibodies should be included in the laboratory checklist for pregnancy. PMID- 26830905 TI - 4-HNE expression in diabetic rat kidneys and the protective effects of probucol. AB - PURPOSE: To investigate 4-HNE expression in diabetic rat kidneys and the protective effect of probucol. METHODS: Diabetic rat models were established. Diabetic rats with successful modeling were randomly divided into the diabetic group (group D) and probucol treated group (group P). Normal rats were put into the control group (group C). Rats in group P were treated with probucol (110 mg/kg day), and rats in groups D and C were given equal volume of water instead. Serum creatinine (SCr), urea nitrogen (BUN), triglyceride (TG), total cholesterol (TC), and 24-h urinary protein were measured at the 4th, 8th, and 12th weeks. Periodic acid-schiff (PAS) staining and hematoxylin-eosin (HE) staining were used to evaluate the renal pathological changes. The immunohistochemistry and Western blot were used to detect 4-HNE expression in renal tissue. RESULTS: The SCr, BUN, TG, TC, and 24-h urinary protein in group D increased in the 4th, 8th, and 12th weeks and were higher than those in group C (P < 0.05). The SCr, BUN, TG, TC, and 24-h urinary protein in group P decreased compared to group D (P < 0.05). Pathological kidney changes in group D were more serious than those in group P. The level of 4-HNE expression in group D significantly increased at the 4th, 8th, and 12th weeks and were higher than those in group C (P < 0.05). In the kidneys treated with probucol, the level of 4-HNE significantly decreased compared to group D (P < 0.05). CONCLUSIONS: Probucol can protect the diabetic kidney by decreasing 4-HNE expression and lipid peroxidation levels. PMID- 26830904 TI - Association of Toll-like receptor 4 (TLR4) with chronic plaque type psoriasis and psoriatic arthritis. AB - Family studies have provided overwhelming evidence for an underlying genetic component to psoriasis. Toll-like receptors (TLRs) are key transmembrane proteins in both the innate and adaptive immune responses which are known to be integral processes in psoriasis. Recent functional studies support this notion having suggested a role for TLR4 in the pathogenesis of psoriasis. Furthermore a missense polymorphism in the TLR4 gene has been associated with a number of autoimmune conditions, including Crohn diseases, making TLR4 a viable candidate gene for investigation. The aim of this study was to investigate polymorphisms across the TLR4 region with a high-density single nucleotide polymorphism (SNP) panel in a large cohort of patients with chronic plaque type psoriasis. Twenty SNPs were successfully genotyped using Sequenom iPLEX Gold platform in 2826 UK chronic plaque type psoriasis patients including subgroup data on presence of confirmed psoriatic arthritis (n = 1839) and early-onset psoriasis (n = 1466) was available. Allele frequencies for psoriasis patients were compared against imputed Wellcome Trust Case Control Consortium controls (n = 4861). Significant association was observed between a missense variant rs4986790 of TLR4 (Asp229Gly) and plaque type psoriasis (p = 2 * 10(-4)) which was also notable in those with psoriatic arthritis (p = 2 * 10(-4)) and early-onset psoriasis (p = 8 * 10(-4)). We present data suggestive of an association between a functional variant and an intronic variant of TLR4 and chronic plaque type psoriasis and psoriatic arthritis. However, validation of this association in independent cohorts will be necessary. PMID- 26830906 TI - Systemic Review of the Feasibility and Advantage of Minimally Invasive Pancreaticoduodenectomy. AB - BACKGROUND: Minimally invasive pancreaticoduodenectomy (MIPD), which includes laparoscopic pancreaticoduodenectomy (LPD) and robotic pancreaticoduodenectomy (RPD), is a complex procedure that needs to be performed by experienced surgeons. However, the safety and oncologic performance have not yet been conclusively determined. METHODS: A systematic literature search was performed using the Embase, Medline, and PubMed databases to identify all studies published up to March 2015. Articles written in English containing the keywords: "pancreaticoduodenectomy" or "Whipple operation" combined with "laparoscopy," "laparoscopic," "robotic," "da vinci," or "minimally invasive surgery" were selected. Furthermore, to increase the power of evidence, articles describing more than ten MIPDs were selected for this review. RESULTS: Twenty-six articles matched the review criteria. A total of 780 LPDs and 248 RPDs were included in the current review. The overall conversion rate to open surgery was 9.1 %. The weighted average operative time was 422.6 min, and the weighted average blood loss was 321.1 mL. The weighted average number of harvested lymph nodes was 17.1, and the rate of microscopically positive tumor margins was 8.4 %. The cumulative morbidity was 35.9 %, and a pancreatic fistula was reported in 17.0 % of cases. The average length of hospital stay was 12.4 days, and the mortality rate was 2.2 %. CONCLUSIONS: In conclusion, after reviewing one-thousand cases in the current literature, we conclude that MIPD offers a good perioperative, postoperative, and oncologic outcome. MIPD is feasible and safe in well-selected patients. PMID- 26830907 TI - In Situ Hypothermic Perfusion of the Liver for Complex Hepatic Resection: Surgical Refinements. AB - INTRODUCTION: While total vascular exclusion (TVE) with veno-venous bypass and hypothermia may be undertaken to increase liver tolerance for complex liver resection, these procedures are still associated with elevated rates of postoperative complications and mortality. In particular, one of the main issues of this strategy is the management of bleeding after declamping, which is enhanced by both hypothermic state and acidosis. To overcome this high risk of morbidity, several technical refinements might be undertaken and here described (with video). METHODS: All patients, requiring TVE >60 min and liver cooling during hepatectomy, were retrospectively included in this study. Technical key points as (a) patient selection, (b) anesthetic management, (c) two-surgeon's technique, (d) preparation for clamping, (e) veno-venous bypass, (f) cooling of the liver, and (g) parenchymal transection, rewarming, and declamping are described and detailed. RESULTS: From 2011 to 2013, we included 8 cases of liver resection with TVE, veno-venous bypass, and hypothermia for malignant disease. Due to the technical refinements, median observed overall blood loss of 550 ml (300-900) including 200 ml (50-300) at declamping and transfusion of packed red blood cell (PRBC) units was required in 5 patients with a mean of 1.25 PRBC/patient. CONCLUSION: The association of TVE, veno-venous bypass, and liver cooling can reduce the time of transection, and blue dye injection and liver rewarming before declamping can reduce blood loss and coagulopathy. Altogether, limited blood loss can be achieved for these complex procedures and may allow to decreasing morbidity. PMID- 26830908 TI - Video-Assisted Thoracoscopic Pulmonary Metastasectomy in Patients with Colorectal Cancer: A Recent 10-Year Single-Institution Experience. AB - INTRODUCTION: The purpose of this study was to identify independent unfavorable prognostic factors for patients who underwent video-assisted thoracoscopic surgery for resection of pulmonary metastases from colorectal cancer (CRC). METHODS: Between January 2004 and December 2013, 131 patients with pulmonary metastases from CRC underwent the aforementioned procedure for the first time at our institution. Kaplan-Meier survival curves and log-rank tests were used to analyze the survival rates. Multivariate analyses were performed using the Cox proportional hazards regression model. RESULTS: The 5-year disease-free survival (DFS) rate of these 131 patients was 34 %. Multivariate analyses showed two variables to be independent significant unfavorable prognostic factors for DFS: preoperative high serum carcinoembryonic antigen (CEA) level and a greater number of pulmonary metastases. According to subgroup analyses that combined these two risk factors, the 5-year DFS rates were 58, 25, and 12 % for patients with 0, 1, or 2 risk factors, respectively. CONCLUSION: In patients who underwent video assisted thoracoscopic surgery for pulmonary metastases from CRC, we identified two independent unfavorable prognostic factors for DFS: a high CEA level before metastasectomy and a greater number of pulmonary metastases. These factors can be used to identify higher- and lower-risk subgroups, which may help with selecting patients who would benefit the most from video-assisted thoracoscopic pulmonary metastasectomy. PMID- 26830909 TI - Abdominal Compartment Syndrome and Intra-abdominal Ischemia in Patients with Severe Acute Pancreatitis. AB - INTRODUCTION: Severe acute pancreatitis may be complicated by intra-abdominal hypertension (IAH), abdominal compartment syndrome (ACS), and intestinal ischemia. The aim of this retrospective study is to describe the incidence, treatment, and outcome of patients with severe acute pancreatitis and ACS, in particular the occurrence of intestinal ischemia. METHODS: The medical records of all patients admitted with severe acute pancreatitis admitted to the ICU of a tertiary referral center were reviewed. The criteria proposed by the World Society of the Abdominal Compartment Syndrome (WSACS) were used to determine whether patients had IAH or ACS. RESULTS: Fifty-nine patients with severe acute pancreatitis were identified. Intra-abdominal pressure (IAP) measurements were performed in 29 patients (49.2 %). IAH was present in all patients (29/29). ACS developed in 13/29 (44.8 %) patients. Ten patients with ACS underwent decompressive laparotomy. A large proportion of patients with ACS had intra abdominal ischemia upon laparotomy: 8/13 (61.5 %). Mortality was high in both the ACS group and the IAH group. CONCLUSION: This study confirms that ACS is common in severe acute pancreatitis. Intra-abdominal ischemia occurs in a large proportion of patients with ACS. Swift surgical intervention may be indicated when conservative measures fail in patients with ACS. National and international guidelines need to be updated so that routine IAP measurements become standard of care for patients with severe acute pancreatitis in the ICU. PMID- 26830910 TI - Virtual patients to explore and develop clinical case summary statement skills amongst Japanese resident physicians: a mixed methods study. AB - BACKGROUND: In Western clinical training, formulation of a summary statement (SS) is a core exercise for articulation, evaluation, and improvement of clinical reasoning (CR). In Japanese clinical training, structured guidance in developing CR, including opportunity for SS practice, is uncommon, and the present status of case summarization skills is unclear. We used Virtual Patients (VPs) to explore Japanese junior residents' SS styles and the effectiveness of VPs on improving SS quality. METHODS: All first-year junior resident physicians at 4 residency programs (n = 54) were assigned randomized sequences of 5 VP modules, rolled out at 6 day intervals. During each module, participants free-texted a case summary and then reviewed a model summary. Thematic analysis was used to identify SS styles and each SS was categorized accordingly. Frequency of SS styles, and SS CR quality determined by 1) an internally developed Key Feature rubric and 2) demonstration of semantic qualification, were compared across modules. RESULTS: Four SS styles were identified: numbered features matched to differential diagnoses, differential diagnoses with supportive comments, feature listing, and narrative summarization. From module #1 to #5, significant increases in the narrative summarization SS style (p = 0.016), SS CR quality score (p = 0.021) and percentage of semantically driven SS (p = 0.003) were observed. CONCLUSIONS: Our study of Japanese junior residents identified distinct clinical case summary statement styles, and observed adoption of the narrative summarization style and improvement in the CR quality of summary statements during a series of VP cases. PMID- 26830911 TI - Predicting analysis times in randomized clinical trials with cancer immunotherapy. AB - BACKGROUND: A new class of immuno-oncology agents has recently been shown to induce long-term survival in a proportion of treated patients. This phenomenon poses unique challenges for the prediction of analysis time in event-driven studies. If the phenomenon of long-term survival is not accounted for properly, the accuracy of the prediction based on the existing methods may be substantially compromised. METHODS: Parametric mixture cure rate models with the best fit to empirical clinical trial data were proposed to predict analysis times in immuno oncology studies during the course of the study. The proposed prediction procedure also accounts for the mechanism of action introduced by cancer immunotherapies, such as delayed and long-term survival effects. RESULTS: The proposed methodology was retrospectively applied to a randomized phase III immuno oncology clinical trial. Among various parametric mixture cure rate models, the Weibull cure rate model was found to be the best-fitting model for this study. The unique survival kinetics of cancer immunotherapy was captured in the longitudinal predictions of the final analysis times. CONCLUSIONS: Parametric mixture cure rate models, along with estimated long-term survival rates, probabilities of study incompletion, and expected statistical powers over time, provide immuno-oncology clinical trial researchers with a useful tool for continuous event monitoring and prediction of analysis times, such that informed decisions with quantifiable risks can be made for better resource and logistic planning. PMID- 26830912 TI - Trends in childhood pneumococcal vaccine coverage in Shanghai, China, 2005-2011: a retrospective cohort study. AB - BACKGROUND: In China, the pneumococcal conjugate vaccine (PCV7) and the pneumococcal polysaccharide vaccine (PPSV23) are not offered under the government's Expanded Program on Immunization and are instead administered for a fee. PCV7 is more effective and covers more serotypes associated with invasive disease in children, but is also more expensive, than PPSV23. Because of their expense, there is concern that these vaccines, especially PCV7, have low uptake particularly among non-locals, migrants from outside of Shanghai. This paper characterizes the differential coverage of PCV7 and PPSV23 between locals and non locals in Shanghai, and illustrates coverage trends over time. METHODS: In this retrospective cohort study, children born between 2005 and 2011 were sampled from the Shanghai Immunization Program Information System. Bivariate and multivariable analyses examined the relationships between demographic characteristics, residency status (non-locals vs locals), and vaccination coverage. RESULTS: PPSV23 coverage (29.8 %) among children over 2 years of age was higher than PCV7 coverage (10.1 %) for locals and non-locals. Uptake of PCV7 increased substantially after children were 2 years of age. Overall, non-local populations had higher PPSV23 coverage (OR: 1.34; 98 % CI: 1.22, 1.46) but lower PCV7 coverage (OR: 0.617, 98 % CI: 0.547, 0.695) than locals. CONCLUSIONS: There is a need for increasing overall pneumococcal coverage in Shanghai children, particularly with the more effective PCV7 vaccine. Morbidity and mortality due to invasive pneumococcal disease for children <1 year of age are unlikely to be mitigated if the current age-related vaccination patterns are not improved. PMID- 26830913 TI - Measurement of wrist flexion and extension torques in different forearm positions. AB - BACKGROUND: Forceful activities of the wrist were considered to be a risk factor for the epicondylitis. However, there are still conflicting evidence concerning work-relatedness of epicondylitis. The main problem is that there is little information about which forearm postures are capable of withstanding higher torque loads and the extent of the differences in the torques generated by different forearm postures. The objective of this study was to investigate the differences in wrist flexion and extension torques among different forearm positions in healthy subjects. METHODS: Twenty wrists of 10 asymptomatic volunteers were evaluated. The apparatus to measure the wrist torque consisted of a handle with a force sensor and a table to place the forearm in different positions. The direction of the handle can change when measuring different forearm positions. The forearm of the examinee was secured to the table. The participants were asked to exert themselves in maximal isometric contraction for wrist flexion or extension, and to maintain it for 5 s. Each evaluation of the flexion and extension torque was conducted twice. Three forearm positions were evaluated: neutral, pronation, and supination. The intra-class correlation coefficients between first and second measurements were evaluated for the maximum torque. The maximum torques and flexion/extension ratio were compared among the positions. In addition, the agility and endurance for the wrist extension/flexion torques were compared among the positions. RESULTS: The intra-class correlation coefficients between first and second measurements were 0.928 and 0.866 for the wrist flexion and extension measurements, respectively. The highest torques for the wrist flexion and extension were observed in the supination and pronation positions, respectively (P < 0.01). There was a higher extension/flexion ratio in the supination position compared to the other positions (P < 0.05). There was a superior agility for the wrist flexion in the supination position compared to the pronation position. CONCLUSIONS: The normal balance of the wrist flexion extension torques in different forearm positions were characterized. This information might aid the provision of advice regarding the optimal positions for performing specific tasks and could help to elucidate the pathophysiology of epicondylitis. PMID- 26830914 TI - Comparison of the pathogen species-specific immune response in udder derived cell types and their models. AB - The outcome of an udder infection (mastitis) largely depends on the species of the invading pathogen. Gram-negative pathogens, such as Escherichia coli often elicit acute clinical mastitis while Gram-positive pathogens, such as Staphylococcus aureus tend to cause milder subclinical inflammations. It is unclear which type of the immune competent cells residing in the udder governs the pathogen species-specific physiology of mastitis and which established cell lines might provide suitable models. We therefore profiled the pathogen species specific immune response of different cell types derived from udder and blood. Primary cultures of bovine mammary epithelial cells (pbMEC), mammary derived fibroblasts (pbMFC), and bovine monocyte-derived macrophages (boMdM) were challenged with heat-killed E. coli, S. aureus and S. uberis mastitis pathogens and their immune response was scaled against the response of established models for MEC (bovine MAC-T) and macrophages (murine RAW 264.7). Only E. coli provoked a full scale immune reaction in pbMEC, fibroblasts and MAC-T cells, as indicated by induced cytokine and chemokine expression and NF-kappaB activation. Weak reactions were induced by S. aureus and none by S. uberis challenges. In contrast, both models for macrophages (boMdM and RAW 264.7) reacted strongly against all the three pathogens accompanied by strong activation of NF-kappaB factors. Hence, the established cell models MAC-T and RAW 264.7 properly reflected key aspects of the pathogen species-specific immune response of the respective parental cell type. Our data imply that the pathogen species-specific physiology of mastitis likely relates to the respective response of MEC rather to that of professional immune cells. PMID- 26830915 TI - Design of the PROUD study: PCR faeces testing in outpatients with diarrhoea. AB - BACKGROUND: Infectious intestinal disease (IID) is an important cause of morbidity in developed countries and a frequent reason for general practitioner (GP) consultation. In recent years polymerase chain reaction (PCR) based techniques have gradually replaced conventional enteropathogen detection techniques like microscopy and culture in primary care patients suspected of IID. PCR features testing of multiple enteropathogens in a single faecal sample with shorter turnaround times and greater sensitivity compared to conventional techniques. However, the associated costs and benefits have not been quantified. Furthermore, primary care incidence and prevalence estimates of enteropathogens associated with IID are sparsely available and predominantly based on conventional techniques. The PROUD-study (PCR diagnostics in Outpatients with Diarrhoea) determines: 1) health (care) effects and 2) cost-effectiveness of PCR introduction in primary care patients suspected of IID; 3) occurrence of major enteropathogens in primary care patients suspected of IID. METHODS: A before after cohort study will be performed of patients with suspected IID consulting a GP in the Utrecht General Practitioner Network (UGPN), covering the before period (2010-2011) with conventional testing and the after period (2013-2014) with PCR testing. Prospective study data on patient characteristics and primary outcome measures (i.e. healthcare use and disease outcome) will be collected from electronic patient and laboratory records in 2015 and 2016. The effect of PCR introduction is investigated by comparing the primary outcome measures and their associated healthcare costs between the conventional period and the PCR period, and is followed by a cost-effectiveness analysis. To determine the occurrence of enteropathogens associated with IID in primary care, routine care faeces samples from the year 2014 will be screened using PCR. DISCUSSION: The PROUD-study will quantify the costs and effects of the introduction of PCR techniques for enteropathogens in primary care patients suspected of IID and generate up-to-date and sensitive estimates of enteropathogen occurrence among primary care patients. PMID- 26830916 TI - The mentoring experiences of new graduate midwives working in midwifery continuity of care models in Australia. AB - The aim of this paper was to explore the mentoring experiences of new graduate midwives working in midwifery continuity of care models in Australia. Most new graduates find employment in hospitals and undertake a new graduate program rotating through different wards. A limited number of new graduate midwives were found to be working in midwifery continuity of care. The new graduate midwives in this study were mentored by more experienced midwives. Mentoring in midwifery has been described as being concerned with confidence building based through a personal relationship. A qualitative descriptive study was undertaken and the data were analysed using continuity of care as a framework. We found having a mentor was important, knowing the mentor made it easier for the new graduate to call their mentor at any time. The new graduate midwives had respect for their mentors and the support helped build their confidence in transitioning from student to midwife. With the expansion of midwifery continuity of care models in Australia mentoring should be provided for transition midwives working in this way. PMID- 26830917 TI - India sees progress in child health but rising obesity, shows health survey. PMID- 26830918 TI - The effect of the duration of intravenous zolendronate medication on the success of non-surgical endodontic therapy: a retrospective study. AB - BACKGROUND: Aim of this study is to compare the clinical and radiographic success of non-surgical endodontic therapy in patients receiving intravenous zolendronate less than 1 year and more than 1 year. METHODS: The clinical and radiographic follow-up data of 24 patients who were receiving IV zolendronate with 37 teeth were retrieved from the archives to evaluate clinical and radiographic healing at the end of 12 months after non-surgical endodontic therapy. The clinical and radiographic scores of teeth treated with non-surgical endodontic therapy were analyzed. RESULTS: The amount of non-healed and incomplete healed teeth in patients receiving zolendronate more than 1 year were more than the amount of teeth of non-healed and incomplete healed in patients receiving bisphosphonates less than 1 year (p <0.05). CONCLUSIONS: There was a strong relationship between the duration of the bisphosphonate medication and endodontic success. PMID- 26830919 TI - Reliability of timed walking tests and temporo-spatial gait parameters in youths with neurological gait disorders. AB - BACKGROUND: The 10-Meter Walk Tests (10MWT) and the 6-Minute Walk Test (6MinWT) are applied to assess gait capacity in paediatric patients. To better objectify changes in qualitative aspects of gait, temporo-spatial parameters like stride length or step symmetry could be simultaneously assessed with a GAITRite system. Reliability has not yet been evaluated in a heterogeneous sample of children with various neurological gait disorders such as is representative for paediatric neuro-rehabilitation. The aim of this study was to assess test-retest reliability of the 10MWT, the 6MinWT and simultaneously recorded gait parameters captured with the GAITRite system in children with neurological gait disorders. METHODS: This is a cross-sectional study with two measurement time-points. Thirty participants (9 females; mean (standard deviation) age 13.0 (3.6) years, 10 with cerebral palsy, 6 after stroke, among other diagnoses) performed the 10MWT at preferred (10MWTpref) and maximum speed (10MWTmax) and the 6MinWT on two occasions (mean time interval: 7.0 (1.9) days). Relative reliability was quantified with an intra-class correlation coefficient (ICC); the measurement error reflecting absolute reliability was quantified with the standard error of measurement and the smallest real difference. RESULTS: ICCs of timed walking tests (time measured with a stopwatch, step count for the 10MWT and walking distance for the 6MinWT) ranged from 0.89-0.97. ICCs of temporo-spatial gait parameters ranged from 0.81-0.95 (10MWTpref), from 0.61-0.90 (10MWTmax) and from 0.88-0.97 (6MinWT). In general, absolute reliability was greatest in the 6MinWT. CONCLUSION: Timed walking tests and temporo-spatial gait parameters obtained from the GAITRite system appear reliable in children with neurological gait disorders. However, especially in children with poorer walking ability, the reliability of temporo-spatial parameters might have been positively influenced, as unclear steps had to be removed using the GAITRite software. As absolute reliability is rather low, the responsiveness of these measures needs to be further evaluated. PMID- 26830920 TI - [Familial acute ascending paralysis recurring with fever]. PMID- 26830921 TI - A hemophagocytosis syndrome attributed to phenobarbital. PMID- 26830922 TI - [Ultra-low dose chest CT: The end of chest radiograph?]. AB - Ultra-low dose chest CT (ULD-CT) is acquired at a radiation dose lowered to that of a PA and lateral chest X-ray. Its image quality is degraded, yet remains diagnostic in many clinical indications. Technological improvements, with iterative reconstruction at the foreground, allowed a strong increase in the image quality obtained with this examination, which is achievable on most recent (<5 years) scanner. Established clinical indications of ULD-CT are increasing, and its non-inferiority compared to the reference "full dose" chest CT are currently demonstrated for the detection of solid nodules, for asbestos-related pleural diseases screening and for the monitoring of infectious pneumonia. Its current limitations are the obese patients (BMI>35) and the interstitial pneumonia, situations in which their performances are insufficient. PMID- 26830923 TI - Transient global amnesia revealing multiple sclerosis. PMID- 26830924 TI - [Primary muscle hydatid cyst: About 3 cases]. PMID- 26830925 TI - [Crohn's disease: Vulvar edema and swelling]. PMID- 26830926 TI - ClinQC: a tool for quality control and cleaning of Sanger and NGS data in clinical research. AB - BACKGROUND: Traditional Sanger sequencing has been used as a gold standard method for genetic testing in clinic to perform single gene test, which has been a cumbersome and expensive method to test several genes in heterogeneous disease such as cancer. With the advent of Next Generation Sequencing technologies, which produce data on unprecedented speed in a cost effective manner have overcome the limitation of Sanger sequencing. Therefore, for the efficient and affordable genetic testing, Next Generation Sequencing has been used as a complementary method with Sanger sequencing for disease causing mutation identification and confirmation in clinical research. However, in order to identify the potential disease causing mutations with great sensitivity and specificity it is essential to ensure high quality sequencing data. Therefore, integrated software tools are lacking which can analyze Sanger and NGS data together and eliminate platform specific sequencing errors, low quality reads and support the analysis of several sample/patients data set in a single run. RESULTS: We have developed ClinQC, a flexible and user-friendly pipeline for format conversion, quality control, trimming and filtering of raw sequencing data generated from Sanger sequencing and three NGS sequencing platforms including Illumina, 454 and Ion Torrent. First, ClinQC convert input read files from their native formats to a common FASTQ format and remove adapters, and PCR primers. Next, it split bar-coded samples, filter duplicates, contamination and low quality sequences and generates a QC report. ClinQC output high quality reads in FASTQ format with Sanger quality encoding, which can be directly used in down-stream analysis. It can analyze hundreds of sample/patients data in a single run and generate unified output files for both Sanger and NGS sequencing data. Our tool is expected to be very useful for quality control and format conversion of Sanger and NGS data to facilitate improved downstream analysis and mutation screening. CONCLUSIONS: ClinQC is a powerful and easy to handle pipeline for quality control and trimming in clinical research. ClinQC is written in Python with multiprocessing capability, run on all major operating systems and is available at https://sourceforge.net/projects/clinqc. PMID- 26830927 TI - The Future of General Surgery: Evolving to Meet a Changing Practice. AB - PURPOSE: Similar to other countries, the practice of General Surgery in Canada has undergone significant evolution over the past 30 years without major changes to the training model. There is growing concern that current General Surgery residency training does not provide the skills required to practice the breadth of General Surgery in all Canadian communities and practice settings. PROCEDURE: Led by a national Task Force on the Future of General Surgery, this project aimed to develop recommendations on the optimal configuration of General Surgery training in Canada. A series of 4 evidence-based sub-studies and a national survey were launched to inform these recommendations. MAIN FINDINGS: Generalized findings from the multiple methods of the project speak to the complexity of the current practice of General Surgery: (1) General surgeons have very different practice patterns depending on the location of practice; (2) General Surgery training offers strong preparation for overall clinical competence; (3) Subspecialized training is a new reality for today's general surgeons; and (4) Generation of the report and recommendations for the future of General Surgery. A total of 4 key recommendations were developed to optimize General Surgery for the 21st century. CONCLUSIONS: This project demonstrated that a high variability of practice dependent on location contrasts with the principles of implementing the same objectives of training for all General Surgery graduates. The overall results of the project have prompted the Royal College to review the training requirements and consider a more "fit for purpose" training scheme, thus ensuring that General Surgery residency training programs would optimally prepare residents for a broad range of practice settings and locations across Canada. PMID- 26830929 TI - Can Multiple Object Tracking Predict Laparoscopic Surgical Skills? AB - OBJECTIVE: The purpose of this study was to examine the relationship between multiple object tracking (MOT) and simulated laparoscopic surgery skills. METHODS: A total of 29 second-year medical students were recruited for this study. The participants completed 3 rounds of a three-dimensional MOT and a simulated laparoscopic surgery task. Averages of the performance on the tasks were calculated. Descriptive variables (i.e., age, hours of sleep, caffeine, and video game use) were measured via questionnaires. Data were analyzed using hierarchical regression models with surgical performance as the outcome variable. Predictor variable was the multiple objects tracking score and the descriptive variables. RESULTS: The regression models revealed a significant prediction of simulated laparoscopic surgical skills by the multiple objects tracking score. In particular, 29% of the variance of time to completion and 28% of the average surgical arm movement were explained. In both regressions, the MOT score was the only significant predictor. CONCLUSION: This study demonstrates the potential implications of perceptual-cognitive training for future surgeons. Along with motor skill practice, MOT may aid to better prepare health care professionals for the complex cognitive demands of surgery. PMID- 26830928 TI - Analysis of Orthopedic Resident Ability to Apply Levels of Evidence Criteria to Scientific Articles. AB - OBJECTIVE: In the era of evidence-based medicine, understanding study design and levels of evidence (LoE) criteria is an important component of resident education and aids practicing surgeons in making informed clinical decisions. The purpose of this study is to analyze the ability of orthopedic residents to accurately determine LoE criteria for published articles compared with medical students. DESIGN: Basic science article. SETTING: Geisinger Medical Center (Danville, PA), tertiary referral center. PARTICIPANTS: Overall, 25 U.S. orthopedic residents and 15 4th year medical students interviewing for a residency position in orthopedic surgery voluntarily participated and provided baseline demographic information. A total of 15 articles from the American Volume of Journal of Bone and Joint Surgery were identified. Study participants were provided with the article title, the abstract, and the complete methods section. The assigned LoE designation was withheld and access to the LoE criteria used by Journal of Bone and Joint Surgery was provided. Each participant was assigned a study type and LoE designation for each article. RESULTS: There were more correct responses regarding the article type (67%) than for LoE designation (39%). For LoE, the intraclass correlation coefficient was 0.30. The percentage of correct responses for article type and LoE increased with more years of training (p = 0.005 and p = 0.002). Although residents had a higher proportion of correct LoE responses overall than medical students, this difference did not reach statistical significance (42% vs. 35%, p = 0.07). CONCLUSIONS: Although improvements in accurately determining both article type and LoE were seen among residents with increasing years of training, residents were unable to demonstrate a statistically significant improvement for determining LoE or article type when compared with medical students. Strategies to improve resident understanding of LoE guidelines need to be incorporated into orthopedic residencies, especially when considering the increased emphasis on evidence-based medicine. PMID- 26830930 TI - Understanding and meeting information needs for patients with posttraumatic stress disorder. AB - BACKGROUND: Posttraumatic Stress Disorder (PTSD) is a commonly occurring mental illness. There are multiple treatments for PTSD that have similar effectiveness, but these treatments differ substantially in other ways. It is desirable to have well-informed patients involved in treatment choices. A patient decision aid (PtDA) is one method to achieve this goal. This manuscript describes the rationale and development of a patient decision aid (PtDA) designed for patients with PTSD. METHODS: We conducted an informational needs assessment of veterans (n = 19) to obtain their baseline information needs prior to the development of the PtDA. We also conducted a literature review of effective PTSD treatments, and we calculated respective effective sizes. A PtDA prototype was developed according to the guidelines from the International Patient Decision Aid Standards. These standards guided our development of both content and format for the PtDA. In accordance with the standards, we gathered feedback from patients (n = 20) and providers (n = 7) to further refine the PtDA. The information obtained from patients and the literature review was used to develop a decision aid for patients with PTSD. RESULTS: Patients with PTSD reported a strong preference to receive information about treatment options. They expressed interest in also learning about PTSD symptoms. The patients preferred information presented in a booklet format. From our literature review several treatments emerged as effective for PTSD: Cognitive Therapy, Exposure Therapy, Eye Movement Desensitization Therapy, Selective Serotonin Reuptake Inhibitors, venlafaxine, and risperidone. CONCLUSION: It appears that the criteria set forth to develop decision aids can effectively be applied to PTSD. The resultant PTSD patient decision aid is a booklet that describes the causes, symptoms, and treatments for PTSD. Future work will examine the effects of use of the PTSD decision aid in clinical practice. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00908440. Registered May 20, 2009. PMID- 26830931 TI - Knock-down and speed of kill of a combination of fipronil and permethrin for the prevention of Ctenocephalides felis flea infestation in dogs. AB - BACKGROUND: A topical combination of fipronil + permethrin (Frontline Tri Act/Frontect, Merial) has recently been developed to control fleas, ticks, mosquitoes, sandflies and stable flies on dogs. Two studies were conducted to assess its speed of kill and knock-down effect on Ctenocephalides felis fleas. The combination was compared to either fipronil alone or to a combination of permethrin, dinotefuran, and pyriproxyfen, METHODS: In each study, 18 dogs were randomly allocated to one of three groups: (Group 1: untreated dog; Group 2: treated once on D0 with the combination of fipronil and permethrin; Group 3: treated once on D0 either with fipronil alone (study 1) or with a combination of permethrin, dinetofuran and pyriproxyfen (study 2)). Each dog was infested with 100 unfed adult C. felis fleas on Days 2 (study 2), 7, 14, 21 and 28. Fleas were collected from dogs at 1 h and 12 h post- infestations (PI) (study 1) or at 2 h and 6 h PI (study 2) to assess efficacy and from collection pans underneath cages 1 h (study 1) or 5 min (study 2) PI to assess knock-down effect. RESULTS: All treated dogs had significantly (p <= 0.01) lower flea counts than untreated dogs at every time point in both studies. For a whole month, a significant knock-down effect against infesting fleas is obtained in five minutes PI with the combination of permethrin and fipronil. Complete efficacy (>95%) was achieved in 1 h (study 1) or 2 h (study 2) PI for 14 days and by 6 h PI for all challenges conducted throughout the month. Efficacy remains >85% at 2 h PI for the whole month. A significantly higher efficacy of the fipronil + permethrin combination compared to other treatments was demonstrated at the earliest time points for the month (1 h knock-down effect and insecticidal efficacy compared to fipronil alone; 5 min knock-down effect compared to the combination of permethrin + dinetofuran + pyriproxyfen). CONCLUSIONS: The rapid flea knock-down effect and speed of kill demonstrated by the spot on combination of fipronil + permethrin provide a reliable strategy against flea infestations in dogs. PMID- 26830932 TI - A novel HYLS1 homozygous mutation in living siblings with Joubert syndrome. AB - The p.Asp211Gly homozygous HYLS1 mutation is so far known to cause only hydrolethalus syndrome, a lethal malformation syndrome. We report living sibling patients with a homozygous no-stop mutation in exon 4 of HYLS1, NM_145014.2:c.900A>C (p.Ter300TyrextTer11) in the second decade of life. The proband has Joubert syndrome (JS). The younger brother also has JS and an enlarged posterior fossa that was initially diagnosed as Dandy-Walker malformation. The present mutation is unique as it affects the stop codon. The product protein HYLS1 plays an essential role in the formation of the primary cilium. This report provides insight into the spectrum of disorders involving midline brain defects closely related to cilium dysfunction or ciliopathy. PMID- 26830933 TI - Putting Gino's lesson to work: Actor-network theory, enacted humanity, and rehabilitation. AB - This article argues that rehabilitation enacts a particular understanding of "the human" throughout therapeutic assessment and treatment. Following Michel Callon and Vololona Rabeharisoa's "Gino's Lesson on Humanity," we suggest that this is not simply a top-down process, but is cultivated in the application and response to biomedical frameworks of human ability, competence, and responsibility. The emergence of the human is at once a materially contingent, moral, and interpersonal process. We begin the article by outlining the basics of the actor network theory that underpins "Gino's Lesson on Humanity." Next, we elucidate its central thesis regarding how disabled personhood emerges through actor-network interactions. Section "Learning Gino's lesson" draws on two autobiographical examples, examining the emergence of humanity through rehabilitation, particularly assessment measures and the responses to them. We conclude by thinking about how rehabilitation and actor-network theory might take this lesson on humanity seriously. PMID- 26830934 TI - Genotypic and phenotypic analysis of clinical isolates of Staphylococcus aureus revealed production patterns and hemolytic potentials unlinked to gene profiles and source. AB - BACKGROUND: Nosocomial infections caused by the bacterial pathogen Staphylococcus aureus can lead to serious complications due to the varying presence of secreted toxins. Comparative studies of genomic information and production rates are needed to assess the pathogenic potential of isolated strains. Genotypic and phenotypic profiling of clinical and colonising isolates of S. aureus was used to characterise the release of exotoxins. Blood isolates were compared with colonisation strains to determine similarities and differences of single strains and clusters. RESULTS: Fifty-one fresh isolates obtained from colonised individuals (n = 29) and S. aureus bacteremia (SAB) patients (n = 22) were investigated. The prevalence of genes encoding for three cytolysins (alpha/beta/gamma toxin) and twenty-four superantigens (SEA-SElX) was determined. Isolates exhibited eighteen distinct combinations of superantigens. Sequence analysis identified mutated open reading frames in hla in 13.7% of all strains, in selw (92.2%) and in selx (15.7%). All corrupted genes were associated with specific clonal complexes. Functional assessment of alpha toxin activity by a rabbit erythrocyte lysis assay revealed that supernatants lacking alpha toxin still displayed hemolysis. This was due to the presence of gamma toxin, as proven by inhibition experiments using antisera raised against the respective recombinant proteins. Alpha toxin, SEC, and TSST1 production was quantified by enzyme-linked immunosorbent assays on supernatants of all hla, sec, and tst positive isolates. Blood isolates and colonising strains showed comparable amounts of secreted proteins within a wide range. Agr types I to IV were identified, but did not allow a prediction of high or low production rates. In contrast, alpha toxin production rates between distinct clonal complexes clearly differed. Spa typing was performed and revealed thirty-two unique spa gene patterns and eight small clusters comprising nineteen isolates. Recognised spa typing clusters displayed highly similar production rates. CONCLUSION: Production rates of the three most prevalent exotoxins varied within both groups of blood isolates and colonising strains. By comparing genotypes and secretion, we found that identical complex gene patterns did not allow predictions of toxin production and function. However, identification of spa typing clusters was suitable to predict similar quantities of released exotoxins. PMID- 26830935 TI - Feasibility of Three-Dimensional MR Angiography Image Fusion Guidance for Endovascular Abdominal Aortic Aneurysm Repair. AB - Magnetic resonance (MR) angiography image fusion (IF) with live fluoroscopy guidance was used while performing endovascular repair of abdominal aortic aneurysm (EVAR) in five patients with a history of chronic renal disease or severe contrast allergy. Intraprocedural technical success was 100%. Median procedure time was 120 minutes (range, 60-180 min), fluoroscopy time was 40 minutes (range, 17-65 min), dose-area product was 245,867 mGy * cm(2) (range, 68,435-690,053 mGy * cm(2)), and iodinated contrast volume injected was 15 mL (range, 0-40 mL). Technical success was achieved in four of five patients (80%); one case was complicated by a type 1 endoleak on follow-up MR angiography, which was successfully treated. EVAR with MR angiography IF guidance was technically feasible and safe in five patients and reduced or eliminated the use of iodinated contrast media. PMID- 26830936 TI - Transcatheter Embolization of Type IA Endoleak after Nellix Endovascular Aortic Aneurysm Sealing with N-Butyl Cyanoacrylate: Technique in Three Patients. AB - The successful transcatheter treatment of a type IA endoleak after endovascular aortic aneurysm sealing with the Nellix EndoVascular Aneurysm Sealing system (Endologix Inc, Irvine, California) using proximal covered stent extension and transarterial N-butyl cyanoacrylate sac embolization is described. Three patients were treated using the same technique with a mean interval between the index procedure and reintervention of 9.3 months (range, 3-15 mo). No complications or endoleaks were seen on follow-up imaging. The mean follow-up time after reintervention was 10.3 months (range, 7-13 mo). PMID- 26830937 TI - Translumbar Tunneled Hemodialysis Line Placement through the Left Gonadal Vein. PMID- 26830938 TI - Microwave Ablation for the Treatment of Hepatic Adenomas. AB - Microwave (MW) ablation was used to treat 12 hepatocellular adenomas in six patients (five women and one man; mean age, 39.6 y). Mean treated tumor size was 2.7 cm +/- 2.0. Tumor response was evaluated with serial cross-sectional imaging for a mean follow-up of 12.6 months +/- 7.1. Primary treatment effectiveness and local tumor control were 100%. There were no instances of hemorrhage, malignant transformation, new hepatic tumors, or extrahepatic metastases. This early experience of treatment of hepatic adenomas by MW ablation demonstrates it to be a safe and feasible treatment modality at short-term follow-up. Continued investigation, including comparison with other treatment modalities, is warranted. PMID- 26830939 TI - Splenic Arteriogastric Fistula. PMID- 26830940 TI - Feasibility of Confocal Laser Microscopy in CT-Guided Needle Biopsy of Pulmonary and Mediastinal Tumors: A Proof-of-Concept Pilot Study. AB - This report describes the use of confocal laser microscopy (CLM) with CT-guided transthoracic needle biopsy (TTNB) for the diagnosis of heterogeneous large mediastinal and lung tumors. The procedure was performed in five patients diagnosed with a mediastinal mass and five patients diagnosed with a lung mass. CLM was used before CT-guided TTNB. Fluorescein administration allowed for the identification of blood vessels in both locations. Malignant cells were identified in mediastinal masses. Complications included one case of pneumothorax. In large tumors, CLM allows vascularized tissue to be differentiated from necrotic and fibrotic areas before biopsy. PMID- 26830941 TI - Ready or Not: Are Medical Students Prepared to Decide between Diagnostic Radiology and IR? PMID- 26830942 TI - Balloon-Assisted Flow Diversion and Selective Catheterization of Target Vessels for Hepatic Transarterial Embolization. PMID- 26830943 TI - Blood Flow Redistribution Using the AMPLATZER Vascular Plug 4 before Distal Pancreatectomy with en Bloc Celiac Axis Resection. PMID- 26830944 TI - Perigraft Injection of N-Butyl 2-Cyanoacrylate to Treat a Persistent Type I Endoleak Occurring after Covered Stent Implantation for a Mycotic Hepatic Artery Aneurysm: A Case Report. PMID- 26830945 TI - Neuroendocrine Malignancy Diagnosed via CT-Guided Percutaneous Biopsy of an Isolated Abnormal Cardiophrenic Lymph Node: Case Report. PMID- 26830946 TI - Treatment of an Infrarenal Aneurysm with an Eccentric Calcified Lesion in the Infrarenal Neck Using the Nellix Endoprosthesis. PMID- 26830947 TI - Transhepatic Embolization of Bilateral Pulmonary Artery Aneurysm with N-Butyl Cyanoacrylate and Coils in Behcet Disease. PMID- 26830948 TI - Crossing a Prostatic Artery Chronic Total Occlusion to Perform Prostatic Arterial Embolization. PMID- 26830949 TI - Comments on: Intrahepatic Activity Distribution in Radioembolization with Yttrium 90-Labeled Resin Microspheres Using the Body Surface Area Method--A Less than Perfect Model. PMID- 26830950 TI - Drs. Grosser et al respond. PMID- 26830951 TI - The Place of Neuroimaging in the Assessment of Cerebral Small Vessel Disease. PMID- 26830952 TI - Risk of hormonotherapy in transgender people: Literature review and data from the French Database of Pharmacovigilance. AB - OBJECTIVE: After the diagnosis of transsexualism, hormone therapy is an established stage of gender identity disorder treatment for inducing secondary sex characteristic development of the target gender while reducing that of the birth sex. The aim of this study was to review existing data about the risk of hormone therapy in transsexual people. METHODS: A PubMed search was done to identify relevant data about adverse drug reactions (ADRs) and mortality associated to hormones exposure. Furthermore, case reports of hormonal therapy induced ADRs were identified in the French Pharmacovigilance DataBase (FPDB). RESULTS: Review of currently available data showed an increase of thromboembolic effects and hyperprolactinemia with oestrogens. Both oestrogens and testosterone derivatives could induce hepatic effects. Currently, there is no significant association between hormone exposure and cancer or mortality in transsexual people. Five ADRs were found in FPDB, and two of them were related to misuse (voluntary overdose and prescription error). CONCLUSION: Potential for under reporting and under-identification in the FPDB of hormonal therapy-induced ADRs in transsexual people should be underlined. Technical improvement of the FPDB could facilitate further identification of reports concerning the risk associated with hormonal therapy in transsexual subjects. PMID- 26830953 TI - Thyroid side effects prophylaxis in front of nuclear power plant accidents. AB - The better knowledge of the mechanisms of nuclear incidents and lessons learned from accidents in the recent past to improve the effectiveness of measures taken following a nuclear accident exposure to fallout of radioactive iodine isotopes. Thus, immediate, passive measures, such as containment, and stopping consumption of contaminated products are paramount. The earliest possible administration of stable iodine as potassium iodide (KI) reduces significantly (up to 90% if taken at the same time of the accident) thyroid radioactive contamination. These tablets should be given in priority to children and pregnant women. The side effects are minor. KI is not recommended for persons aged over 60 years, or for adults suffering from cardiovascular disorders. PMID- 26830955 TI - [Vertebral collapse revealing primary hyperparathyroidism in a 14-year-old girl]. AB - Primary hyperparathyroidism, widely prevalent in women after menopause, remains rare in children and adolescents. Sporadic forms are the most frequent. Clinical manifestations are general, renal, gastrointestinal, cardiac, or bony. Diagnosis is biological and radiological. The imaging modalities allow assessment of the disease impact and identification of the parathyroid adenoma. PMID- 26830954 TI - A practical review of magnetic resonance imaging for the evaluation and management of cervical cancer. AB - Cervical cancer is a leading cause of mortality in women worldwide. Staging and management of cervical cancer has for many years been based on clinical exam and basic imaging such as intravenous pyelogram and x-ray. Unfortunately, despite advances in radiotherapy and the inclusion of chemotherapy in the standard plan for locally advanced disease, local control has been unsatisfactory. This situation has changed only recently with the increasing implementation of magnetic resonance image (MRI)-guided brachytherapy. The purpose of this article is therefore to provide an overview of the benefits of MRI in the evaluation and management of cervical cancer for both external beam radiotherapy and brachytherapy and to provide a practical approach if access to MRI is limited. PMID- 26830956 TI - [Nutritional status in pediatric intermediate care: Assessment at admission, progression during the stay and after discharge]. AB - INTRODUCTION: Malnutrition, known as a cause of morbidity, has not been studied in children admitted to pediatric intermediate care units. This study aimed to describe the association between patients' nutritional status and the relative severity of illness that characterizes this population. PATIENTS AND METHODS: In this prospective longitudinal study, a dedicated nutrition support team assessed the nutritional status of all children, aged 5 days to 18 years, admitted to our university pediatric intermediate care unit (Hopital Femme-Mere-Enfants, Lyon, France) over one year (2012-2013). Weight, height, body mass index, weight-for age ratio, height-for-age ratio, and the analysis of growth curves were collected at admission. We monitored patients' weight, which allowed us to detect malnutrition occurrence during the stay, and its progression up to 3 months after discharge. RESULTS: A total of 459 patients were enrolled. Based on the analysis integrating all nutritional indices and the progression of growth curves, malnutrition at admission was detected in 23.8% of children (20.5% and 6.8% suffered from acute and chronic malnutrition, respectively). Based only on the body mass index, malnutrition was detected in 15.5% of children. Chronic disease appeared as a risk factor for malnutrition at admission (P=0.0001) and young age for acute malnutrition (P=0.04). The incidence of acquired malnutrition during the stay (in children with a length of stay > 5 days) was up to 26%, and dyspnea was the only risk factor identified. This population recovered with a normal nutritional status late (66% after 2 months and 16% after 3 months). CONCLUSIONS: The prevalence of malnutrition is high in our pediatric intermediate care unit. The occurrence of acquired malnutrition during the stay is frequent. All children should benefit from systematic nutritional assessment at admission as well as careful monitoring during the stay and after discharge, to adapt early and individualized nutritional support. PMID- 26830957 TI - [Evaluation of pre-travel prevention and morbidity in child travelers]. AB - International travel is growing, but few data exist on prevention for children traveling. The aim of this study was to describe a population of children traveling from France to countries outside Europe and to evaluate the quality of prevention and healthcare services provided for these travelers. MATERIALS AND METHODS: We conducted a retrospective epidemiological study in three pediatric emergency departments in Paris from August to October 2009 and 2012. Data were collected retrospectively from anonymous questionnaires proposed to families consulting emergency services, irrespective of their reason, who had recently traveled (in the year preceding travel outside the European Union). RESULTS: Of the 166 children included, who for the most part had traveled to visit relatives and friends in Sub-Saharan Africa and North Africa, 76% of their families were from the destination countries, 78% had received prevention counseling, mostly with their doctor. They had been vaccinated against yellow fever, but the hepatitis A vaccine was neglected. The preventive measures had been difficult to achieve in practice. During travel, 54% of children had health problems (39% diarrhea, 29% vomiting, 31% fever) prompting medical care in 28%, 5% were admitted to a hospital, and 4% had return to France earlier than planned. In epidemic areas, 13% of children had malaria. CONCLUSION: There is poor counseling on basic prevention (hygiene, diarrhea, malaria, immunization). Time constraints in pediatricians and competing priorities could explain this problem. The challenge for healthcare providers to reduce these pathologies is to provide services of sufficient quality and clarity. All medical stakeholders have an important role to play. PMID- 26830958 TI - Long-term Marijuana Use and Cognitive Impairment in Middle Age. PMID- 26830959 TI - Systematic review: the influence of nasal obstruction on sleep apnea. AB - INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a common disorder that can lead to cardiovascular morbidity and mortality, as well as to metabolic, neurological, and behavioral consequences. It is currently believed that nasal obstruction compromises the quality of sleep when it results in breathing disorders and fragmentation of sleep. However, recent studies have failed to objectively associate sleep quality and nasal obstruction. OBJECTIVE: The aim of this systematic review is to evaluate the influence of nasal obstruction on OSAS and polysomnographic indices associated with respiratory events. METHODS: Eleven original articles published from 2003 to 2013 were selected, which addressed surgical and non-surgical treatment for nasal obstruction, performing polysomnography type 1 before and after the intervention. RESULTS/CONCLUSIONS: In most trials, nasal obstruction was not related to the apnea-hypopnea index (AHI), indicating no improvement in OSAS with reduction in nasal resistance. However, few researchers evaluated other polysomnography indices, such as the arousal index and rapid eye movement (REM) sleep percentage. These could change with nasal obstruction, since it is possible that the nasal obstruction does not completely block the upper airways, but can increase negative intrathoracic pressure, leading to sleep fragmentation. PMID- 26830960 TI - Perturbations in Effort-Related Decision-Making Driven by Acute Stress and Corticotropin-Releasing Factor. AB - Acute stress activates numerous systems in a coordinated effort to promote homeostasis, and can exert differential effects on mnemonic and cognitive functions depending on a myriad of factors. Stress can alter different forms of cost/benefit decision-making, yet the mechanisms that drive these effects, remain unclear. In the present study, we probed how corticotropin-releasing factor (CRF) may contribute to stress-induced alterations in cost/benefit decision-making, using an task where well-trained rats chose between a low effort/low reward lever (LR; two pellets) and a high effort/high reward lever (HR; four pellets), with the effort requirement increasing over a session (2, 5, 10, and 20 presses). One hour restraint stress markedly reduced preference for the HR option, but this effect was attenuated by infusions of the CRF antagonist, alpha-helical CRF. Conversely, central CRF infusion mimicked the effect of stress on decision making, as well as increased decision latencies and reduced response vigor. CRF infusions did not alter preference for larger vs smaller rewards, but did reduce responding for food delivered on a progressive ratio, suggesting that these treatments may amplify perceived effort costs that may be required to obtain rewards. CRF infusions into the ventral tegmental area recapitulated the effect of central CRF treatment and restraint on choice behavior, suggesting that these effects may be mediated by perturbations in dopamine transmission. These findings highlight the involvement of CRF in regulating effort-related decisions and suggest that increased CRF activity may contribute to motivational impairments and abnormal decision-making associated with stress-related psychiatric disorders such as depression. PMID- 26830962 TI - Sixteen-month-olds can use language to update their expectations about the visual world. AB - The capacity to use language to form new representations and to revise existing knowledge is a crucial aspect of human cognition. Here we examined whether infants can use language to adjust their representation of a recently encoded scene. Using an eye-tracking paradigm, we asked whether 16-month-old infants (N=26; mean age=16;0 [months;days], range=14;15-17;15) can use language about an occluded event to inform their expectation about what the world will look like when the occluder is removed. We compared looking time to outcome scenes that matched the language input with looking time to those that did not. Infants looked significantly longer at the event outcome when the outcome did not match the language input, suggesting that they generated an expectation of the outcome based on that input alone. This effect was unrelated to infants' vocabulary size. Thus, using language to adjust expectations about the visual world is present at an early developmental stage even when language skills are rudimentary. PMID- 26830961 TI - Moderate Stress-Induced Social Bonding and Oxytocin Signaling are Disrupted by Predator Odor in Male Rats. AB - In times of stress, social support can serve as a potent buffering mechanism that enhances resilience. In humans, stress can promote protective affiliative interactions and prosocial behavior. Yet, stress also precipitates psychopathologies characterized by social withdrawal such as post-traumatic stress disorder (PTSD) and depression. The factors that drive adaptive vs maladaptive social responses to stress are not yet clear. Rodent studies have focused on pair-bonded, opposite-sex mates and suggest that a variety of stressors can induce social support-like behaviors. However, between same-sex conspecifics-particularly males-stress effects on social bonding are less understood and often associated with aggression and social unrest. We thus sought to investigate if a moderate stressor-3 h of acute immobilization-impacts social support behaviors differently when experienced in a neutral vs more innately threatening context (ie, paired with predator odor). We found that moderate stress increased social support-seeking behavior in rat cagemates and facilitated long-term sharing of a limited water resource, decreased aggression, and strongly defined dominance ranks (an indicator of home cage stability). In contrast, experiencing the same stressor in the presence of predator odor eliminated the positive behavioral effects of moderate stress. Importantly, hypothalamic oxytocin (OT) signaling increased coincident with stress in a neutral-but not a predator odor-context. Our results define a novel rodent model of divergent stress effects on social affiliation and OT signaling dependent on odor context with particularly strong relevance to stress-related disorders such as PTSD, which are characterized by a disrupted ability to seek and maintain social bonds. PMID- 26830963 TI - Multiple Non-Equivalent Interfaces Mediate Direct Activation of GABAA Receptors by Propofol. AB - BACKGROUND: Propofol is a sedative agent that at clinical concentrations acts by allosterically activating or potentiating the gamma-aminobutyric acid type A (GABAA) receptor. Mutational, modeling, and photolabeling studies with propofol and its analogues have identified potential interaction sites in the transmembrane domain of the receptor. At the "+" of the beta subunit, in the beta-alpha interface, meta-azipropofol labels the M286 residue in the third transmembrane domain. Substitution of this residue with tryptophan results in loss of potentiation by propofol. At the "-" side of the beta subunit, in the alpha-beta interface (or beta-beta interface, in the case of homomeric beta receptors), ortho-propofol diazirine labels the H267 residue in the second transmembrane domain. Structural modeling indicates that the beta(H267) residue lines a cavity that docks propofol with favorable interaction energy. METHOD: We used two-electrode voltage clamp to determine the functional effects of mutations to the "+" and "-" sides of the beta subunit on activation of the alpha1beta3 GABAA receptor by propofol. RESULTS: We found that while the individual mutations had a small effect, the combination of the M286W mutation with tryptophan mutations of selected residues at the alpha-beta interface leads to strong reduction in gating efficacy for propofol. CONCLUSION: We conclude that alpha1beta3 GABAA receptors can be activated by propofol interactions with the beta-beta, alpha-beta, and beta-alpha interfaces, where distinct, non-equivalent regions control channel gating. Any interface can mediate activation, hence substitutions at all interfaces are required for loss of activation by propofol. PMID- 26830966 TI - Early eradication of factor VIII inhibitor in patients with congenital hemophilia A by immune tolerance induction with a high dose of immunoglobulin. AB - The production of factor VIII (FVIII) inhibitory antibodies is a serious problem in patients with hemophilia A. Immune tolerance induction (ITI) is the only strategy proven to eradicate persistent inhibitors and has been shown to be successful in 70 % of patients with hemophilia A. However, a minority of hemophilia patients present life-long inhibitors. To eliminate such inhibitors, we designed an intravenous immunoglobulin (IVIG) strategy in combination with high dose recombinant FVIII for ITI in hemophilia A children with inhibitors. Four previously untreated patients produced inhibitors within 16 exposures to FVIII. The peak inhibitor titers in these patients ranged from 3 to 14 BU/mL. The patients received ITI combined with IVIG within 1.5 months after the inhibitors were detected. All patients showed a negative titer for inhibitors by 28 days, with no anamnestic responses. The recovery of FVIII in the plasma concentration was normalized within three months after initiation of ITI. An additional course of IVIG administration led to induction of complete tolerance by 20 months after initiation of ITI therapy in all patients. ITI treatment with high-dose FVIII combined with IVIG may be effective for the early elimination of inhibitors. PMID- 26830964 TI - Synaptic Plasticity, Metaplasticity and Depression. AB - The development of a persistent depressive affective state has for some time been thought to result from persistent alterations in neurotransmitter-mediated synaptic transmission. While the identity of those transmitters has changed over the years, the literature has lacked mechanistic connections between the neurophysiological mechanisms they regulate, and how these mechanisms alter neuronal function, and, hence, affective homeostasis. This review will examine recent work that suggests that both long-term activity-dependent changes in synaptic strength ("plasticity"), and shifting set points for the ease of induction of future long-term changes ("metaplasticity"), may be critical to establishing and reversing a depressive behavioral state. Activitydependent long term synaptic plasticity involves both strengthening and weakening of synaptic connections associated with a dizzying array of neurochemical alterations that include synaptic insertion and removal of a number of subtypes of AMPA, NMDA and metabotropic glutamate receptors, changes in presynaptic glutamate release, and structural changes in dendritic spines. Cellular mechanisms of metaplasticity are far less well understood. Here, we will review the growing evidence that long term synaptic changes in glutamatergic transmission, in brain regions that regulate mood, are key determinants of affective homeostasis and therapeutic targets with immense potential for drug development. PMID- 26830967 TI - Genetic variations in complement factors in patients with congenital thrombotic thrombocytopenic purpura with renal insufficiency. AB - The congenital form of thrombotic thrombocytopenic purpura (TTP) is caused by genetic mutations in ADAMTS13. Some, but not all, congenital TTP patients manifest renal insufficiency in addition to microangiopathic hemolysis and thrombocytopenia. We included 32 congenital TTP patients in the present study, which was designed to assess whether congenital TTP patients with renal insufficiency have predisposing mutations in complement regulatory genes, as found in many patients with atypical hemolytic uremic syndrome (aHUS). In 13 patients with severe renal insufficiency, six candidate complement or complement regulatory genes were sequenced and 11 missense mutations were identified. One of these missense mutations, C3:p.K155Q mutation, is a rare mutation located in the macroglobulin-like 2 domain of C3, where other mutations predisposing for aHUS cluster. Several of the common missense mutations identified in our study have been reported to increase disease-risk for aHUS, but were not more common in patients with as compared to those without renal insufficiency. Taken together, our results show that the majority of the congenital TTP patients with renal insufficiency studied do not carry rare genetic mutations in complement or complement regulatory genes. PMID- 26830968 TI - TLc-A, the leading nanochelating-based nanochelator, reduces iron overload in vitro and in vivo. AB - Iron chelation therapy is an effective approach to the treatment of iron overload conditions, in which iron builds up to toxic levels in the body and may cause organ damage. Treatments using deferoxamine, deferasirox and deferiprone have been introduced and despite their disadvantages, they remain the first-line therapeutics in iron chelation therapy. Our study aimed to compare the effectiveness of the iron chelation agent TLc-A, a nano chelator synthetized based on the novel nanochelating technology, with deferoxamine. We found that TLc A reduced iron overload in Caco2 cell line more efficiently than deferoxamine. In rats with iron overload, very low concentrations of TLc-A lowered serum iron level after only three injections of the nanochelator, while deferoxamine was unable to reduce iron level after the same number of injections. Compared with deferoxamine, TLc-A significantly increased urinary iron excretion and reduced hepatic iron content. The toxicity study showed that the intraperitoneal median lethal dose for TLc-A was at least two times higher than that for deferoxamine. In conclusion, our in vitro and in vivo studies indicate that the novel nano chelator compound, TLc-A, offers superior performance in iron reduction than the commercially available and widely used deferoxamine. PMID- 26830969 TI - Short sleep duration and serum copper. PMID- 26830970 TI - Vasopressin-induced Ca(2+) signals in human adipose-derived stem cells. AB - Intracellular Ca(2+) signals are essential for stem cell differentiation due to their ability to control signaling pathways involved in this process. Arginine vasopression (AVP) is a neurohypophyseal hormone that increases intracellular Ca(2+) concentration during adipogenesis via V1a receptors, Gq-proteins and the PLC-IP3 pathway in human adipose-derived stromal/stem cells (hASCs). These Ca(2+) signals originate through calcium release from pools within the endoplasmic reticulum and the extracellular space. AVP supplementation to the adipogenic media inhibits adipogenesis and key adipocyte marker genes. This review focuses on the intersection between AVP, Ca(2+) signals and ASC differentiation. PMID- 26830972 TI - Erratum: The assembly dynamics of the cytolytic pore toxin ClyA. PMID- 26830971 TI - Severe impairment of male reproductive organ development in a low SMN expressing mouse model of spinal muscular atrophy. AB - Spinal muscular atrophy (SMA) is caused by low levels of survival motor neuron (SMN), a multifunctional protein essential for higher eukaryotes. While SMN is one of the most scrutinized proteins associated with neurodegeneration, its gender-specific role in vertebrates remains unknown. We utilized a mild SMA model (C/C model) to examine the impact of low SMN on growth and development of mammalian sex organs. We show impaired testis development, degenerated seminiferous tubules, reduced sperm count and low fertility in C/C males, but no overt sex organ phenotype in C/C females. Underscoring an increased requirement for SMN expression, wild type testis showed extremely high levels of SMN protein compared to other tissues. Our results revealed severe perturbations in pathways critical to C/C male reproductive organ development and function, including steroid biosynthesis, apoptosis, and spermatogenesis. Consistent with enhanced apoptosis in seminiferous tubules of C/C testes, we recorded a drastic increase in cells with DNA fragmentation. SMN was expressed at high levels in adult C/C testis due to an adult-specific splicing switch, but could not compensate for low levels during early testicular development. Our findings uncover novel hallmarks of SMA disease progression and link SMN to general male infertility. PMID- 26830974 TI - Plasmon-enhanced two-photon-induced isomerization for highly-localized light based actuation of inorganic/organic interfaces. AB - Two-photon initiated photo-isomerization of an azobenzene moiety adsorbed on silver nanoparticles (Ag NPs) is demonstrated. The azobenzene is linked to a materials-binding peptide that brings it into intimate contact with the Ag NP surface, producing a dramatic enhancement of its two-photon absorbance. An integrated modeling approach, combining advanced conformational sampling with Quantum Mechanics/Capacitance Molecular Mechanics and response theory, shows that charge transfer and image charges in the Ag NP generate local fields that enhance two-photon absorption of the cis isomer, but not the trans isomer, of adsorbed molecules. Moreover, dramatic local field enhancement is expected near the localized surface plasmon resonance (LSPR) wavelength, and the LSPR band of the Ag NPs overlaps the azobenzene absorbance that triggers cis to trans switching. As a result, the Ag NPs enable two-photon initiated cis to trans isomerization, but not trans to cis isomerization. Confocal anti-Stokes fluorescence imaging shows that this effect is not due to local heating, while the quadratic dependence of switching rate on laser intensity is consistent with a two-photon process. Highly localized two-photon initiated switching could allow local manipulation near the focal point of a laser within a 3D nanoparticle assembly, which cannot be achieved using linear optical processes. PMID- 26830973 TI - The influence of genetic variants of sorafenib on clinical outcomes and toxic effects in patients with advanced renal cell carcinoma. AB - The purpose of the present study was to investigate whether genetic variants that influence angiogenesis and sorafenib pharmacokinetics are associated with clinical outcomes and toxic effects in advanced renal cell carcinoma patients treated with this drug. One hundred patients with advanced renal cell carcinoma were enrolled. Forty-two polymorphisms in 15 genes were selected for genotyping and analyzed for associations with progression-free survival, overall survival, and toxic effects. We found that rs1570360 in VEGF and rs2239702 in VEGFR2 were significantly associated with progression-free. Specifically, patients carrying the variant genotypes (AG + AA) of these two polymorphisms both had an unfavorable progression-free. In addition, compared with those with the rs2239702 GG genotype, patients with the AG + AA genotype suffered an unfavorable OS. We found that the VEGF rs2010963 CG + GG genotypes had a significantly increased risk of hand-foot syndrome, and the ABCB1 rs1045642 CT + TT genotypes had an increased risk of high blood pressure. Our results suggest that polymorphisms in VEGF and VEGFR2 are associated with sorafenib clinical outcomes, and polymorphisms in VEGF and ABCB1 are associated with sorafenib-related toxicities. Larger studies are warranted to validate our findings. PMID- 26830975 TI - Will delayed release metformin provide better management of diabetes type 2? PMID- 26830976 TI - Does Sex Matter in the Clinical Presentation of Eating Disorders in Youth? AB - PURPOSE: Eating disorders (EDs) impact both males and females, but little is known about sex differences in ED psychopathology and overall clinical presentation. This study compared demographic and clinical characteristics of child and adolescent males and females who presented for ED treatment. METHODS: Participants included 619 youth (59 males and 560 females) ages 6-18 years who presented for treatment between 1999 and 2011. RESULTS: Males presented for ED treatment at a significantly younger age (p < .001), earlier age of onset (p = .004), and were more likely to be nonwhite (p = .023). Females showed more severe ED pathology across the Eating Disorder Examination subscales (weight concern: p < .001; eating concern: p < .001; restraint: p = .001; and shape concern: p = .019) and global score (p < .001). Males were more likely to present with an ED other than anorexia nervosa or bulimia nervosa (p = .002). Females presented with significantly higher rates of mood disorders (p = .027) and had a lower average percent of expected body weight (p = .020). Males and females did not differ in duration of illness, prior hospitalization or treatment, binging and purging episodes, anxiety disorders, behavioral disorders, or self-esteem. All analyses were controlled for age. CONCLUSIONS: Results indicate that further exploration into why the sexes present differently may be warranted. Developing ED psychopathology assessments that better capture nuances particular to males and reevaluating criteria to better categorize male ED diagnoses may allow for more targeted treatment. PMID- 26830977 TI - Bacterial Muramyl Dipeptide (MDP) Restricts Human Cytomegalovirus Replication via an IFN-beta-Dependent Pathway. AB - We recently reported that induction of NOD2 by human Cytomegalovirus (HCMV) resulted in virus inhibition and upregulation of antiviral and inflammatory cytokines. Here we investigated the effects of muramyl dipeptide (MDP), a bacterial cell wall component that activates NOD2, on HCMV replication and antiviral responses. HCMV infection of human foreskin fibroblasts induced NOD2, the downstream receptor-interacting serine/threonine-protein kinase 2 (RIPK2), resulting in phosphorylation of TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3). MDP treatment following infection at low multiplicity (MOI = 0.1 PFU/cell) inhibited HCMV in a dose-dependent manner and further induced phosphorylation of TBK1, IRF3 and expression of IFN-beta. None of these effects of MDP were observed following infection at multiplicity of 1. In infected NOD2 knocked-down cells MDP did not induce IFN-beta, irrespective of MOI. Treatment with MDP before infection also inhibited HCMV, an effect augmented with treatment duration. Treatment with an IFN-beta receptor blocking antibody or knockdown of IFN-beta significantly attenuated the inhibitory effect of MDP on HCMV. MDP treatment before or after infection with herpesvirus 1 did not inhibit its replication. Summarized, NOD2 activation exerts anti-HCMV activities predominantly via IFN-beta. Since MDP is a bacterial cell wall component, ongoing microbial exposure may influence HCMV replication. PMID- 26830978 TI - Resistance switching behavior of atomic layer deposited SrTiO3 film through possible formation of Sr2Ti6O13 or Sr1Ti11O20 phases. AB - Identification of microstructural evolution of nanoscale conducting phase, such as conducting filament (CF), in many resistance switching (RS) devices is a crucial factor to unambiguously understand the electrical behaviours of the RS based electronic devices. Among the diverse RS material systems, oxide-based redox system comprises the major category of these intriguing electronic devices, where the local, along both lateral and vertical directions of thin films, changes in oxygen chemistry has been suggested to be the main RS mechanism. However, there are systems which involve distinctive crystallographic phases as CF; the Magneli phase in TiO2 is one of the very well-known examples. The current research reports the possible presence of distinctive local conducting phase in atomic layer deposited SrTiO3 RS thin film. The conducting phase was identified through extensive transmission electron microscopy studies, which indicated that oxygen-deficient Sr2Ti6O13 or Sr1Ti11O20 phase was presumably present mainly along the grain boundaries of SrTiO3 after the unipolar set switching in Pt/TiN/SrTiO3/Pt structure. A detailed electrical characterization revealed that the samples showed typical bipolar and complementary RS after the memory cell was unipolar reset. PMID- 26830980 TI - Sharing Clinical Trial Data: A Proposal from the International Committee of Medical Journal Editors. PMID- 26830979 TI - Microbial profiles at baseline and not the use of antibiotics determine the clinical outcome of the treatment of chronic periodontitis. AB - Antibiotics are often used in the treatment of chronic periodontitis, which is a major cause of tooth loss. However, evidence in favour of a microbial indication for the prescription of antibiotics is lacking, which may increase the risk of the possible indiscriminate use of antibiotics, and consequent, microbial resistance. Here, using an open-ended technique, we report the changes in the subgingival microbiome up to one year post-treatment of patients treated with basic periodontal therapy with or without antibiotics. Antibiotics resulted in a greater influence on the microbiome 3 months after therapy, but this difference disappeared at 6 months. Greater microbial diversity, specific taxa and certain microbial co-occurrences at baseline and not the use of antibiotics predicted better clinical treatment outcomes. Our results demonstrate the predictive value of specific subgingival bacterial profiles for the decision to prescribe antibiotics in the treatment of periodontitis, but they also indicate the need for alternative therapies based on ecological approaches. PMID- 26830981 TI - Efficacy and Safety of "URSA Complex" in Subjects with Physical Fatigue: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial. AB - BACKGROUND: Fatigue is a common symptom both in diseases status and in healthy subjects. Various supplements and nutraceuticals for relieving of fatigue have been used. However, there are a few studies to evaluate the efficacy and the safety of the drug for fatigue alleviation, we conducted using URSA Complex to evaluate the efficacy on physical fatigue via score changes in the checklist individual strength (CIS). METHODS: The study was designed as a multicenter, randomized, double-blind, placebo-controlled trial, with subjects randomized to one of the two arms, receiving either placebo or URSA Complex administered as identical capsules. The primary efficacy endpoints of this clinical trials are the ratio of improving CIS scores < 76 points in patients at the end (4 weeks). Secondary efficacy variables are as follows one is an improvement of fatigue and the other is an improvement of the liver enzyme. RESULTS: The fatigue recovery rate in who had improved CIS scores of < 76 points were 70.0%, 50.9% in the therapy group and placebo group, respectively (P = 0.019). The fatigue recovery rate in CIS score was higher in URSA Complex therapy group than placebo group. The difference between therapy group and placebo group was statistically significant at 4 weeks later, but not 2 weeks. CONCLUSIONS: Our results provided that the URSA Complex was effective in alleviating physical fatigue. The adverse event frequency in the therapy groups was similar to that in the placebo group. PMID- 26830982 TI - Impact of Clinical Guideline Recommendations on the Application of Coronary Computed Tomographic Angiography in Patients with Suspected Stable Coronary Artery Disease. AB - BACKGROUND: Coronary computed tomographic angiography (CCTA) has been widely used in patients who are at intermediate risk for having stable coronary artery disease (SCAD), and 2013 European Society of Cardiology Guidelines on the Management of SCAD (2013G) recommended the appropriate application of CCTA. However, 2013G has not been subjected to systematic analyses for subsequent impact on clinical practice. METHODS: A total of 5320 patients suspected with SCAD were enrolled and scheduled for CCTA from March 2013 to September 2014. For each patient, pretest probability of SCAD was calculated according to updated Diamond-Forrester model (UDFM). Appropriate CCTA or appropriate stress test was determined as described in the 2013G. A generalized estimating equation model was used to determine the trends in the half-monthly rate of appropriate CCTA. RESULTS: Overall, only 61.37% of patients received appropriate CCTA, and there was insignificant change over time (P = 0.8701). The application of CCTA in patients who should have had a stress test accounted for most of the inappropriate CCTA before (22.29%) or after (19.98%) the publication of the 2013G. In all patients or any subgroup, no significant change in the adjusted half-monthly rate of appropriate CCTA was found after the publication of the 2013G (odds ratio, 1.002; 95% confidence interval, 0.982-1.021; P = 0.8678). CONCLUSIONS: These findings suggest that the 2013G have not, to date, been fully incorporated into clinical practice, and the clinical utilization of CCTA remains unreasonable to some extent. PMID- 26830983 TI - A Historical Cohort Study on the Efficacy of Glucocorticoids and Riboflavin Among Patients with Late-onset Multiple Acyl-CoA Dehydrogenase Deficiency. AB - BACKGROUND: Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common type of lipid storage myopathies in China. Most patients with late onset MADD are well responsive to riboflavin. Up to now, these patients are often treated with glucocorticoids as the first-line drug because they are misdiagnosed as polymyositis without muscle biopsy or gene analysis. Although glucocorticoids seem to improve the fatty acid metabolism of late-onset MADD, the objective evaluation of their rationalization on this disorder and comparison with riboflavin treatment are unknown. METHODS: We performed a historical cohort study on the efficacy of the two drugs among 45 patients with late-onset MADD, who were divided into glucocorticoids group and riboflavin group. Detailed clinical information of baseline and 1-month follow-up were collected. RESULTS: After 1 month treatment, a dramatic improvement of muscle strength was found in riboflavin group (P < 0.05). There was no significant difference in muscle enzymes between the two groups. Significantly, the number of patients with full recovery in glucocorticoids group was less than the number in riboflavin group (P < 0.05). On the other hand, almost half of the patients in riboflavin group still presented high-level muscle enzymes and weak muscle strength after 1-month riboflavin treatment, meaning that 1-month treatment duration maybe insufficient and patients should keep on riboflavin supplement for a longer time. CONCLUSIONS: Our results provide credible evidences that the overall efficacy of riboflavin is superior to glucocorticoids, and a longer duration of riboflavin treatment is necessary for patients with late-onset MADD. PMID- 26830984 TI - The Hug-up Test: A New, Sensitive Diagnostic Test for Supraspinatus Tears. AB - BACKGROUND: The supraspinatus tendon is the most commonly affected tendon in rotator cuff tears. Early detection of a supraspinatus tear using an accurate physical examination is, therefore, important. However, the currently used physical tests for detecting supraspinatus tears are poor diagnostic indicators and involve a wide range of sensitivity and specificity values. Therefore, the aim of this study was to establish a new physical test for the diagnosis of supraspinatus tears and evaluate its accuracy in comparison with conventional tests. METHODS: Between November 2012 and January 2014, 200 consecutive patients undergoing shoulder arthroscopy were prospectively evaluated preoperatively. The hug-up test, empty can (EC) test, full can (FC) test, Neer impingement sign, and Hawkins-Kennedy impingement sign were used and compared statistically for their accuracy in terms of supraspinatus tears, with arthroscopic findings as the gold standard. Muscle strength was precisely quantified using an electronic digital tensiometer. RESULTS: The prevalence of supraspinatus tears was 76.5%. The hug-up test demonstrated the highest sensitivity (94.1%), with a low negative likelihood ratio (NLR, 0.08) and comparable specificity (76.6%) compared with the other four tests. The area under the receiver operating characteristic curve for the hug-up test was 0.854, with no statistical difference compared with the EC test (z = 1.438, P = 0.075) or the FC test (z = 1.498, P = 0.067). The hug-up test showed no statistical difference in terms of detecting different tear patterns according to the position (chi2 = 0.578, P = 0.898) and size (Fisher's exact test, P > 0.999) compared with the arthroscopic examination. The interobserver reproducibility of the hug-up test was high, with a kappa coefficient of 0.823. CONCLUSIONS: The hug-up test can accurately detect supraspinatus tears with a high sensitivity, comparable specificity, and low NLR compared with the conventional clinical tests and could, therefore, improve the diagnosis of supraspinatus tears in clinical settings. PMID- 26830985 TI - Effect of Right Heart Systolic Function on Outcomes in Patients with Constrictive Pericarditis Undergoing Pericardiectomy. AB - BACKGROUND: To determine the influence of right ventricular function in patients with constrictive pericarditis (CP) undergoing surgery and to compare the outcomes of patients who received surgery with those managed medically. METHODS: Patients with the diagnosis of CP and healthy volunteers were recruited from January 2006 to November 2011. Patients with CP chose to either receive pericardiectomy or medical management. Echocardiographic measurements were performed to evaluate heart function, and survival was recorded. RESULTS: A total of 58 patients with CP (36 received pericardiectomy, 22 managed medically), and 43 healthy volunteers were included. CP patients who received surgery had a higher survival rate than those managed medically (P = 0.003), and higher survival was also seen in the subgroup of CP patients with severely impaired right systolic function. Albumin level, left ventricular end-diastolic dimension, and tricuspid regurgitation velocity were associated with survival in CP patients who received surgery. CONCLUSIONS: Preoperative right heart function does not affect surgical outcomes. Patients with severely impaired preoperative right systolic function obtain a greater survival advantage with surgery than with medical treatment. PMID- 26830986 TI - Computer Navigation-aided Resection of Sacral Chordomas. AB - BACKGROUND: Resection of sacral chordomas is challenging. The anatomy is complex, and there are often no bony landmarks to guide the resection. Achieving adequate surgical margins is, therefore, difficult, and the recurrence rate is high. Use of computer navigation may allow optimal preoperative planning and improve precision in tumor resection. The purpose of this study was to evaluate the safety and feasibility of computer navigation-aided resection of sacral chordomas. METHODS: Between 2007 and 2013, a total of 26 patients with sacral chordoma underwent computer navigation-aided surgery were included and followed for a minimum of 18 months. There were 21 primary cases and 5 recurrent cases, with a mean age of 55.8 years old (range: 35-84 years old). Tumors were located above the level of the S3 neural foramen in 23 patients and below the level of the S3 neural foramen in 3 patients. Three-dimensional images were reconstructed with a computed tomography-based navigation system combined with the magnetic resonance images using the navigation software. Tumors were resected via a posterior approach assisted by the computer navigation. Mean follow-up was 38.6 months (range: 18-84 months). RESULTS: Mean operative time was 307 min. Mean intraoperative blood loss was 3065 ml. For computer navigation, the mean registration deviation during surgery was 1.7 mm. There were 18 wide resections, 4 marginal resections, and 4 intralesional resections. All patients were alive at the final follow-up, with 2 (7.7%) exhibiting tumor recurrence. The other 24 patients were tumor-free. The mean Musculoskeletal Tumor Society Score was 27.3 (range: 19-30). CONCLUSIONS: Computer-assisted navigation can be safely applied to the resection of the sacral chordomas, allowing execution of preoperative plans, and achieving good oncological outcomes. Nevertheless, this needs to be accomplished by surgeons with adequate experience and skill. PMID- 26830987 TI - Comparison of Clinical and Ultrasonographic Features of Poorly Differentiated Thyroid Carcinoma and Papillary Thyroid Carcinoma. AB - BACKGROUND: The clinical behavior and management of poorly differentiated thyroid carcinoma (PDTC) are very different from papillary thyroid carcinoma (PTC). By comparing the clinical and ultrasonographic features between the two tumors, we proposed to provide more possibilities for recognizing PDTC before treatment. METHODS: The data of 13 PDTCs and 39 age- and gender-matched PTCs in Peking Union Medical College Hospital between December 2003 and September 2013 were retrospectively reviewed. The clinical and ultrasonic features between the two groups were compared. RESULTS: The frequencies of family history of carcinoma, complication with other thyroid lesions, lymph node metastases, recurrent laryngeal nerve injuries, and distant metastases were higher in PDTCs (30.8%, 61.6%, 69.2%, 23.1%, and 46.2%, respectively) than those in PTCs (2.6%, 23.1%, 25.6%, 2.6%, and 2.6%, respectively) (P < 0.05). The mortality rate of PDTCs was greatly higher than PTCs (P < 0.01). Conventional ultrasound showed that the size of PDTCs was larger than that of PTCs (3.1 +/- 1.9 cm vs. 1.7 +/- 1.0 cm). Clear margins and rich and/or irregular blood flow were found in 92.3% of PDTCs, which differed substantially from PTCs (51.7% and 53.8%, respectively) (P < 0.05). CONCLUSIONS: PDTC is more aggressive and its mortality rate is higher than PTCs. Accordingly, more attention should be given to suspicious thyroid cancer nodules that show large size, regular shape, and rich blood flow signals on ultrasound to exclude the possibility of PDTCs. PMID- 26830988 TI - Study of Clinical and Genetic Risk Factors for Aspirin-induced Gastric Mucosal Injury. AB - BACKGROUND: Current knowledge about clinical and genetic risk factors for aspirin induced gastric mucosal injury is not sufficient to prevent these gastric mucosal lesions. METHODS: We recruited aspirin takers as the exposed group and healthy volunteers as the control group. The exposed group was categorized into two subgroups such as subgroup A as gastric mucosal injury diagnosed by gastroscopy, including erosion, ulcer or bleeding of the esophagus, stomach, or duodenum; subgroup B as no injury of the gastric mucosa was detected by gastroscopy. Clinical information was collected, and 53 single nucleotide polymorphisms were evaluated. RESULTS: Among 385 participants, 234 were in the aspirin-exposed group. According to gastroscopy, 82 belonged to subgroup A, 91 belonged to subgroup B, and gastroscopic results of 61 participants were not available. Using the Chi-square test and logistic regression, we found that peptic ulcer history (odds ratio [OR] = 5.924, 95% confidence intervals [CI]: 2.115-16.592), dual anti platelet medication (OR = 3.443, 95% CI: 1.154-10.271), current Helicobacter pylori infection (OR = 2.242, 95% CI: 1.032-4.870), male gender (OR = 2.211, 95% CI: 1.027-4.760), GG genotype of rs2243086 (OR = 4.516, 95% CI: 1.180-17.278), and AA genotype of rs1330344 (OR = 2.178, 95% CI: 1.016-4.669) were more frequent in subgroup A than subgroup B. In aspirin users who suffered from upper gastrointestinal bleeding, the frequency of the TT genotype of rs2238631 and TT genotype of rs2243100 was higher than in those without upper gastrointestinal bleeding. CONCLUSIONS: Peptic ulcer history, dual anti-platelet medication, H. pylori current infection, and male gender were possible clinical risk factors for aspirin-induced gastric mucosal injury. GG genotype of rs2243086 and AA genotype of rs1330344 were possible genetic risk factors. TT genotype of rs2238631 and TT genotype of rs2243100 may be risk factors for upper gastrointestinal bleeding in aspirin users. PMID- 26830989 TI - A Pilot Study of Quantitative Loop-mediated Isothermal Amplification-guided Target Therapies for Hospital-acquired Pneumonia. AB - BACKGROUND: It is important to achieve the definitive pathogen identification in hospital-acquired pneumonia (HAP), but the traditional culture results always delay the target antibiotic therapy. We assessed the method called quantitative loop-mediated isothermal amplification (qLAMP) as a new implement for steering of the antibiotic decision-making in HAP. METHODS: Totally, 76 respiratory tract aspiration samples were prospectively collected from 60 HAP patients. DNA was isolated from these samples. Specific DNA fragments for identifying 11 pneumonia related bacteria were amplified by qLAMP assay. Culture results of these patients were compared with the qLAMP results. Clinical data and treatment strategies were analyzed to evaluate the effects of qLAMP results on clinical data. McNemar test and Fisher's exact test were used for statistical analysis. RESULTS: The detection of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Stenotrophomonas maltophilia, Streptococcus pneumonia, and Acinetobacter baumannii by qLAMP was consistent with sputum culture (P > 0.05). The qLAMP results of 4 samples for Haemophilus influenzae, Legionella pneumophila, or Mycoplasma pneumonia (MP) were inconsistent with culture results; however, clinical data revealed that the qLAMP results were all reliable except 1 MP positive sample due to the lack of specific species identified in the final diagnosis. The improvement of clinical condition was more significant (P < 0.001) in patients with pathogen target-driven therapy based on qLAMP results than those with empirical therapy. CONCLUSION: qLAMP is a more promising method for detection of pathogens in an early, rapid, sensitive, and specific manner than culture. PMID- 26830990 TI - Comparison of Serum Adiponectin in Smoke-induced Pulmonary Emphysema Rats Fed Different Diets. AB - BACKGROUND: Smoking and body mass index (BMI) are the key risk factors for chronic obstructive pulmonary disease (COPD). Adiponectin with both anti inflammatory and pro-inflammatory properties is a vital modulator of inflammatory processes, which is expressed in epithelial cells in the airway in COPD emphysema. The aim of this study was to examine the effects of adiponectin on tobacco smoke-induced emphysema in rats, which were fed different diets. METHODS: Seventy-six adult (6-8 weeks old) male Sprague-Dawley rats (average weight 220 +/ 20 g) were exposed to smoke or smoke-free room atmosphere and fed different diets (regular, high-fat, or low-fat diets) for 6 months. The rats were randomly divided into six groups. They are nonsmoke-exposed regular diet (n = 10), nonsmoke-exposed high-fat diet (n = 14), nonsmoke-exposed low-fat diet (n = 14), smoke-exposed regular diet (n = 10), smoke-exposed high-fat diet (n = 14), and smoke-exposed low-fat diet groups (n = 14). A full 2 3 factorial design was used to evaluate the effect of independent variables on smoke exposure and different rearing methods. Serum adiponectin and inflammatory cytokines were measured by the enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum adiponectin levels in rats fed low-fat and regular diets exposed to smoke exposure were remarkably higher than that of rats exposed to room air while serum adiponectin levels of fat-rich diet rats exposed to tobacco smoke were lower than that of rats exposed to room air. Compared with regular diet or low-fat diet group, serum adiponectin levels in high-fat diet rats exposed to tobacco smoke were lower (t = 6.932, 11.026; all P < 0.001). BMI was inversely correlated with serum adiponectin levels (r = -0.751, P = 0.012). Serum interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and 4-hydroxy 2-nonenal (HNE) levels in rats exposed to low fat or fat-rich diets were remarkably higher than that of rats exposed to normal diets (IL-6, t = 4.196, 3.480; P < 0.01, P = 0.001; TNF-alpha, t = 4.286, 3.521; P < 0.01, P = 0.001; 4-HNE, t = 4.298, 4.316; all P < 0.001). In nonhigh-fat diet rats exposed to tobacco smoke, serum adiponectin levels correlated positively with serum IL-6, TNF-alpha, and 4-HNE, bronchoalveolar lavage cell count, and mean linear intercept. In contrast, in high-fat diet rats, serum adiponectin levels correlated inversely with these parameters. CONCLUSIONS: In smoke-induced emphysema and fat-rich diet rat model, serum adiponectin level was decreased, and the anti-inflammatory effect was attenuated. By contrast, nonhigh-fat diet elevated serum adiponectin and enhanced the role of pro-inflammatory. PMID- 26830991 TI - Biosafety of the Novel Vancomycin-loaded Bone-like Hydroxyapatite/Poly-amino Acid Bony Scaffold. AB - BACKGROUND: Recently, local sustained-release antibiotics systems have been developed because they can increase local foci of concentrated antibiotics without increasing the plasma concentration, and thereby effectively decrease any systemic toxicity and side effects. A vancomycin-loaded bone-like hydroxyapatite/poly-amino acid (V-BHA/PAA) bony scaffold was successfully fabricated with vancomycin-loaded poly lactic-co-glycolic acid microspheres and BHA/PAA, which was demonstrated to exhibit both porosity and perfect biodegradability. The aim of this study was to systematically evaluate the biosafety of this novel scaffold by conducting toxicity tests in vitro and in vivo. METHODS: According to the ISO rules for medical implant biosafety, for in vitro tests, the scaffold was incubated with L929 fibroblasts or rabbit noncoagulant blood, with simultaneous creation of positive control and negative control groups. The growth condition of L929 cells and hemolytic ratio were respectively evaluated after various incubation periods. For in vivo tests, a chronic osteomyelitis model involving the right proximal tibia of New Zealand white rabbits was established. After bacterial identification, the drug-loaded scaffold, drug-unloaded BHA/PAA, and poly (methyl methacrylate) were implanted, and a blank control group was also set up. Subsequently, the in vivo blood drug concentrations were measured, and the kidney and liver functions were evaluated. RESULTS: In the in vitro tests, the cytotoxicity grades of V-BHA/PAA and BHA/PAA based on the relative growth rate were all below 1. The hemolysis ratios of V BHA/PAA and BHA/PAA were 2.27% and 1.42%, respectively, both below 5%. In the in vivo tests, the blood concentration of vancomycin after implantation of V-BHA/PAA was measured at far below its toxic concentration (60 mg/L), and the function and histomorphology of the liver and kidney were all normal. CONCLUSION: According to ISO standards, the V-BHA/PAA scaffold is considered to have sufficient safety for clinical utilization. PMID- 26830992 TI - Expression of Potassium Channels in Uterine Smooth Muscle Cells from Patients with Adenomyosis. AB - BACKGROUND: Adenomyosis (AM) has impaired contraction. This study aimed to explore the expression of potassium channels related to contraction in myometrial smooth muscle cells (MSMCs) of AM. METHODS: Uterine tissue samples from 22 patients (cases) with histologically confirmed AM and 12 (controls) with cervical intraepithelial neoplasia were collected for both immunohistochemistry and real time polymerase chain reaction to detect the expression of large conductance calcium- and voltage-sensitive K + channel (BKCa)-alpha/beta subunits, voltage gated potassium channel (Kv) 4.2, and Kv4.3. Student's t-test was used to compare the expression. RESULTS: The BKCa-alpha/beta subunits, Kv4.2, and Kv4.3 were located in smooth muscle cells, glandular epithelium, and stromal cells. However, BKCa-beta subunit expression in endometrial glands of the controls was weak, and Kv4.3 was almost undetectable in the controls. The expression of BKCa-alpha messenger RNA (mRNA) (0.62 +/- 0.19-fold decrease, P < 0.05) and Kv4.3 mRNA (0.67 +/- 0.20-fold decrease, P < 0.05) decreased significantly in the MSMCs of the control group compared with the AM group. However, there were no significant differences in BKCa-beta subunit mRNA or Kv4.2 mRNA. CONCLUSIONS: The BKCa-alpha mRNA and the Kv4.3 mRNA are expressed significantly higher in AM than those in the control group, that might cause the abnormal uterus smooth muscle contractility, change the microcirculation of uterus to accumulate the inflammatory factors, impair the endometrium further, and aggravate the pain. PMID- 26830993 TI - Surface Modification of Intraocular Lenses. AB - OBJECTIVE: This paper aimed to review the current literature on the surface modification of intraocular lenses (IOLs). DATA SOURCES: All articles about surface modification of IOLs published up to 2015 were identified through a literature search on both PubMed and ScienceDirect. STUDY SELECTION: The articles on the surface modification of IOLs were included, but those on design modification and surface coating were excluded. RESULTS: Technology of surface modification included plasma, ion beam, layer-by-layer self-assembly, ultraviolet radiation, and ozone. The main molecules introduced into IOLs surface were poly (ethylene glycol), polyhedral oligomeric silsesquioxane, 2-methacryloyloxyethyl phosphorylcholine, TiO 2 , heparin, F-heparin, titanium, titanium nitride, vinyl pyrrolidone, and inhibitors of cytokines. The surface modification either resulted in a more hydrophobic lens, a more hydrophilic lens, or a lens with a hydrophilic anterior and hydrophobic posterior surface. Advances in research regarding surface modification of IOLs had led to a better biocompatibility in both in vitro and animal experiments. CONCLUSION: The surface modification is an efficient, convenient, economic and promising method to improve the biocompatibility of IOLs. PMID- 26830996 TI - Intestinal Duplication Cyst Misdiagnosed as Meckel's Diverticulum. PMID- 26830997 TI - Experience in Clinical Assessment of a Suspected Ebola Patient Manifesting with Acute Abdomen. PMID- 26830995 TI - Malposition of Central Venous Catheter: Presentation and Management. PMID- 26830994 TI - Carotid Intima-media Thickness Measurements: Relations with Atherosclerosis, Risk of Cardiovascular Disease and Application in Randomized Controlled Trials. AB - Advances in the field of carotid ultrasound have been incremental, resulting in a steady decrease in measurement variability. Improvements in edge detection algorithms point toward increasing automation of CIMT measurements. The major advantage of CIMT is that it is completely noninvasive and can be repeated as often as required. It provides a continuous measure since all subjects have a measurable carotid wall. It is also relatively inexpensive to perform, and the technology is widely available. A graded relation between raising LDL cholesterol and increased CIMT is apparent. Increased CIMT has been shown consistently to relate the atherosclerotic abnormalities elsewhere in the arterial system. Moreover, increased CIMT predicts future vascular events in both populations from Caucasian ancestry and those from Asian ancestry. Furthermore, lipid-lowering therapy has been shown to affect CIMT progression within 12-18 months in properly designed trials with results congruent with clinical events trials. In conclusion, when one wants to evaluate the effect of a pharmaceutical intervention that is to be expected to beneficially affect atherosclerosis progression and to reduce CV event risk, the use of CIMT measurements over time is a valid, suitable, and evidence-based choice. PMID- 26830998 TI - Coronary Computed Tomographic Angiography for Suspected Stable Coronary Artery Disease: Gap Between the 2013 European Society of Cardiology Guideline Recommendations and Clinical Practice. PMID- 26830999 TI - Psychiatric Symptoms in Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation Syndrome and its Treatment: A Case Report. PMID- 26831000 TI - Leukemia Study in Sulaymaniyah Province, Kurdistan, Iraq. PMID- 26831001 TI - Massive Hematochezia Following Blunt Trauma in a Patient with Crohn's Disease: Intraluminal Bleeding without Hemoperitoneum. PMID- 26831002 TI - Rasmussen's Encephalitis with Faciobrachial Dystonic Attacks and Bilateral Hemispheric Involvement. PMID- 26831003 TI - A Case of Juxtaglomerular Cell Tumor of the Kidney Treated with Retroperitoneal Laparoscopy Partial Nephrectomy. PMID- 26831004 TI - Obstructive Sleep Apnea Hypopnea Syndrome and Pulmonary Embolism: Warfarin Versus Positive Airway Pressure as Determinant. PMID- 26831005 TI - Obstructive Sleep Apnea Hypopnea Syndrome: An Incognito Player Contributing to Repeated Pulmonary Embolism? PMID- 26831006 TI - The predictive power of serum S-100B for non-sentinel node positivity in melanoma patients. AB - BACKGROUND: Completion lymph node dissection (CLND) in sentinel node (SN) positive melanoma patients leads to substantial morbidity and costs, while only approximately 20% have a metastasis in non-sentinel nodes (NSNs). The aim of this study was to investigate if the biomarkers S-100B and Lactate Dehydrogenase (LDH) are associated with NSN positivity, to identify patients in whom CLND could safely be omitted. METHODS: All SN positive patients who underwent CLND at the University Medical Centre Groningen between January 2004 and January 2015 were analysed. Patient and tumor characteristics, and serum S-100B and LDH values measured the day before CLND were statistically tested for their association with NSN positivity. RESULTS: NSN positivity was found in 20.6% of the 107 patients undergoing CLND. Univariate analysis revealed male gender (p = 0.02), melanoma of the lower extremity (p = 0.05), Breslow thickness (p = 0.004), ulceration (p = 0.04), proportion of involved SNs (p = 0.045) and S-100B value (p = 0.01) to be associated with NSN positivity. LDH level was not significantly associated with positive NSNs (p = 0.39). In multivariable analysis, S-100B showed to have the strongest association with NSN positivity, within its reference interval of 0.20 MUg/l (p = 0.02, odds ratio 5.71, 95% confidence interval 1.37-23.87). CONCLUSION: In this study, the preoperatively measured S-100B value is the strongest predictor for NSN positivity in patients planned for CLND. Fluctuations of the S-100B level within the reference interval might give important clues about residual tumor load. Although further validation will be needed, this new closer look of S-100B could be of value in patient selection for CLND in the future. PMID- 26831007 TI - Whole-body magnetic resonance imaging in myxoid liposarcoma: A useful adjunct for the detection of extra-pulmonary metastatic disease. AB - Myxoid liposarcomas (MLS) are a subgroup of soft-tissue sarcomas which have a propensity for extra-pulmonary metastases. Conventional radiological staging of soft-tissue sarcomas consists of chest radiographs (CXR) and thoracic computed tomography (CT) for possible chest metastases, supplemented by magnetic resonance imaging (MRI) for local disease. The optimal radiological modality to detect extra-pulmonary metastases for systemic staging has not been proven. We reviewed the efficacy of Whole-Body MRI (WBMRI) for this purpose. 33 WBMRI and simultaneous CT scans were performed in 28 patients suffering from MLS between 2007 and 2015. 38 metastases were identified in seven patients via WBMRI. Osseous lesions predominated (spine, pelvis, chest-wall and long bones), followed by soft tissue and abdominal lesions. Of the 29 soft-tissue or osseous metastases that were within the field-of-view of the simultaneous CT scans, five soft-tissue and zero osseous metastases were identified using CT. Metastatic disease was detected in three patients solely using WBMRI, which directly influenced their management. WBMRI is a useful adjunct in the detection of extra-pulmonary metastatic disease, which directly alters patient management. WBMRI has demonstrated an ability to identify more sites of metastatic disease compared to CT. WBMRI should be used in two situations. Firstly, at diagnosis where ablative treatment will be required e.g. amputation, when the diagnosis of occult metastasis would change treatment planning. Secondly, at diagnosis of relapse to confirm if it is a solitary site of relapse prior to consideration of metastectomy. PMID- 26831008 TI - Effect of physical activity on levels of homocysteine, folate, and vitamin B12 in the elderly. AB - OBJECTIVES: Homocysteine (Hcy) has emerged as a risk factor for cardiovascular diseases (CVD). However the relationship of physical activity (PA) with Hcy levels in the elderly is controversial. Accordingly, the current study examined the effect of low and high participation in PA on serum Hcy in young (n = 77; 18 50 years) and old (n = 207; > 65 years) males (n = 141) and females (n = 142). METHODS: Level of PA was obtained in a 1-to-1 interview and participants divided into low and high groups. Serum Hcy, folate, and vitamin B12 were obtained after 12 hour fast drawn by venipuncture. RESULTS: Levels of Hcy correlated with folate (r = -0. 5; p = 0.000) and vitamin B12 (r = -0.3; p = 0.000). The ANOVA revealed a main effect of PA for Hcy (p = 0.04) but not for folate (p = 0.2) and vitamin B12 (p = 0.2). Main effects were found also of age for Hcy (p = 0.000) and folate (p = 0.005) as well as of gender for Hcy (p = 0.000) and vitamin B12 (p = 0.000). Subsequent ANCOVA showed lower levels of Hcy in the participants with greater versus lower PA even after controlling for B12 vitamin. CONCLUSION: These results confirm the importance of the vitamins for regulating Hcy levels. Additionally, the data suggests that PA affects Hcy levels without affecting and independent of B vitamins in the elderly. PMID- 26831009 TI - SncRNA (microRNA &snoRNA) opposite expression pattern found in multiple sclerosis relapse and remission is sex dependent. AB - Multiple sclerosis (MS) is a common inflammatory and degenerative disease that causes neurological disability. It affects young adults and its prevalence is higher in women. The most common form is manifested as a series of acute episodes of neurological disability (relapses) followed by a recovery phase (remission). Recently, non-coding RNAs have emerged as new players in transcriptome regulation, and in turn, they could have a significant role in MS pathogenesis. In this context, our aim was to investigate the involvement of microRNAs and snoRNAs in the relapse-remission dynamics of MS in peripheral blood leucocytes, to shed light on the molecular and regulatory mechanisms that underlie this complex process. With this approach, we found that a subset of small non-coding RNAs (sncRNA) is altered in relapse and remission, revealing unexpected opposite changes that are sex dependent. Furthermore, we found that a relapse-related miRNA signature regulated general metabolism processes in leucocytes, and miRNA altered in remission are involved in the regulation of innate immunity. We observed that sncRNA dysregulation is different in relapse and remission leading to differences in transcriptome regulation, and that this process is sex dependent. In conclusion, relapse and remission have a different molecular background in men and women. PMID- 26831011 TI - Teaching children with autism to tell socially appropriate lies. AB - This study used a nonconcurrent multiple baseline across participants design to evaluate the use of rules, role-play, and feedback for teaching 3 children with autism spectrum disorder to tell socially appropriate lies when (a) presented with an undesired gift and (b) someone's appearance changed in an undesired way. The intervention was effective in teaching use of socially appropriate lies, and generalization to untrained people and gifts or appearances was observed. PMID- 26831010 TI - Identification of two novel Chlorotoxin derivatives CA4 and CTX-23 with chemotherapeutic and anti-angiogenic potential. AB - Brain tumors are fast proliferating and destructive within the brain microenvironment. Effective chemotherapeutic strategies are currently lacking which combat this deadly disease curatively. The glioma-specific chloride ion channel represents a specific target for therapy. Chlorotoxin (CTX), a peptide derived from scorpion venom, has been shown to be specific and efficacious in blocking glioma Cl(-) channel activity. Here, we report on two new derivatives (termed CA4 and CTX-23) designed and generated on the basis of the peptide sequence alignments of CTX and BmKCT. The novel peptides CA4 and CTX-23 are both effective in reducing glioma cell proliferation. In addition, CTX, CA4 and CTX-23 impact on cell migration and spheroid migration. These effects are accompanied by diminished cell extensions and increased nuclear sizes. Furthermore, we found that CA4 and CTX-23 are selective with low toxicity against primary neurons and astrocytes. In the ex vivo VOGiM, which maintain the entire brain tumor microenvironment, both CTX and CA4 display anti-tumor activity and reduce tumor volume. Hence, CTX and CA4 reveal anti-angiogenic properties with endothelial and angiogenic hotspots disrupting activities. These data report on the identification of two novel CTX derivatives with multiple anti-glioma properties including anti-angiogenesis. PMID- 26831012 TI - The vomeronasal organ - incidence in a Bulgarian population. AB - BACKGROUND: The vomeronasal organ is an accessory olfactory organ found in vertebrates that specialises in the chemoreception of pheromones. This study aimed to explore the existence and occurrence of the vomeronasal organ in adult humans. METHODS: A total of 966 consecutive video recordings of out-patient nasopharyngolaryngoscopies performed at the St Marina University Hospital, Varna, Bulgaria, were retrospectively reviewed. RESULTS: Data analysis showed that from the evaluable cases, the organ was evident on the left side of the nasal septum in 14.93 per cent, on the right side in 21.15 per cent and bilaterally in 2.35 per cent of cases. The vomeronasal organ was present in a total of 26.83 per cent of the investigated subjects. CONCLUSION: More research should be focused on revealing the incidence and functionality of the organ, and on its preservation in surgical manipulations that affect the nasal septum and other nearby structures. PMID- 26831013 TI - Serum Autotaxin Levels Are Associated with Proteinuria and Kidney Lesions in Japanese Type 2 Diabetic Patients with Biopsy-proven Diabetic Nephropathy. AB - Objective We evaluated the relationships between the serum autotaxin (ATX) levels and the clinical and pathological parameters, as well as the long-term renal outcome, in type 2 diabetic patients with biopsy-proven diabetic nephropathy. Methods In this retrospective single-center cohort study, serum samples were collected from 38 Japanese type 2 diabetic patients with biopsy-proven diabetic nephropathy at the time of renal biopsy. The serum ATX levels were measured using a specific sandwich enzyme immunoassay. Results A multivariate linear regression analysis revealed the urinary protein excretion to be independently associated with the serum ATX levels. In addition, patients with serum ATX levels above the median showed more advanced diffuse lesions, nodular lesions and arteriolar hyalinosis compared to those with serum ATX levels below the median. However, high serum ATX levels were not associated with any increase in the number of renal composite events [a need for dialysis or a 50% decline in the estimated glomerular filtration rate (eGFR) from baseline]. Conclusion The serum ATX levels in type 2 diabetic patients with diabetic nephropathy were associated with proteinuria and diabetic kidney lesions, although the serum ATX levels were not identified to be a predictive indicator for the renal outcome. PMID- 26831014 TI - The Neutrophil to Lymphocyte Ratio Is Related to Disease Severity and Exacerbation in Patients with Chronic Obstructive Pulmonary Disease. AB - Objective Although chronic obstructive pulmonary disease (COPD) is characterized by systemic inflammation, the association between the neutrophil to lymphocyte ratio (NLR; an indicator of inflammation) and the clinical status of COPD has not been well studied. We hypothesized that the NLR is associated with disease severity and exacerbation in COPD patients. Methods We performed blood testing, pulmonary function testing, chest computed tomography, a body composition analysis, and a 6-minute walk test and applied the modified Medical Research Council (MMRC) dyspnea scale for 141 stable COPD patients. In addition, we calculated the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index to evaluate the disease severity. Finally, we examined the association between the NLR and clinical parameters in stable COPD patients, and we further investigated changes in the NLR between exacerbation and the stable state. Results The NLR was positively correlated with the BODE index, extent of emphysema, and MMRC score (p<0.001 for all), while inversely correlated with airflow obstruction (p<0.001), body mass index (p<0.001), fat-free mass index (p=0.001), and the 6-minute walk distance (p<0.001). We obtained the NLR during exacerbation from 49 patients. The NLR was significantly higher at exacerbation compared to the stable state (p<0.001). Conclusion The NLR was associated with disease severity and exacerbation in COPD patients. Therefore, the usefulness of the NLR in COPD patients should be elucidated in clinical settings in future investigations. PMID- 26831015 TI - Beneficial Effects of Ramelteon on Rapid Eye Movement Sleep Behavior Disorder Associated with Parkinson's Disease - Results of a Multicenter Open Trial. AB - Objective Melatonin is effective for treating patients with rapid eye movement sleep behavior disorder (RBD). Ramelteon, a novel hypnotic, acts as a melatonin receptor agonist. In the current study, we investigated the effects of ramelteon on sleep disorders, including RBD, in patients with Parkinson's disease (PD). Methods We evaluated 35 patients from multiple centers with idiopathic PD accompanied by sleep disturbances (age: 69.1+/-11.1 years; 17 men, 18 women; PD morbidity: 6.9+/-5.7 years; Hoehn & Yahr stage: 2.5+/-0.8; levodopa dose equivalent: 561+/-401 mg/day). The patients received 8 mg of ramelteon before sleep once daily for 12 weeks. Motor and sleep symptoms were evaluated both before and after ramelteon administration. Results Of the 35 patients enrolled in this study, 24 (68.6%) were diagnosed with probable RBD (pRBD) using the Japanese version of the RBD screening questionnaire. Ramelteon administration reduced the severity of sleep disturbances in patients with PD. It also lowered scores on the Japanese version of the RBD questionnaire in patients with PD and pRBD. Conclusion Ramelteon may have beneficial effects on sleep disturbances, especially on RBD in patients with PD. PMID- 26831016 TI - Detection of Left Ventricular Regional Dysfunction and Myocardial Abnormalities Using Complementary Cardiac Magnetic Resonance Imaging in Patients with Systemic Sclerosis without Cardiac Symptoms: A Pilot Study. AB - Objective We sought to detect the presence of left ventricular regional dysfunction and myocardial abnormalities in systemic sclerosis (SSc) patients without cardiac symptoms using a complementary cardiac magnetic resonance (CMR) imaging approach. Methods Consecutive patients with SSc without cardiac symptoms and healthy controls underwent CMR on a 1.5 T scanner. The peak systolic regional function in the circumferential and radial strain (Ecc, % and Err, %) were calculated using a feature tracking analysis on the mid-left ventricular slices obtained with cine MRI. In addition, we investigated the myocardial characteristics by contrast MRI. Pharmacological stress and rest perfusion scans were performed to assess perfusion defect (PD) due to micro- or macrovascular impairment, and late gadolinium enhancement (LGE) images were obtained for the assessment of myocarditis and/or fibrosis. Results We compared 15 SSc patients with 10 healthy controls. No statistically significant differences were observed in the baseline characteristics between the patients and healthy controls. The mean peak Err and Ecc of all segments was significantly lower in the patients than the controls (p=0.011 and p=0.003, respectively). Four patients with LGE (28.6%) and seven patients with PD (50.0%) were observed. PD was significantly associated with digital ulcers (p=0.005). Utilizing a linear regression model, the presence of myocardial LGE was significantly associated with the peak Ecc (p=0.024). After adjusting for age, the association between myocardial LGE and the peak Ecc was strengthened. Conclusion A subclinical myocardial involvement, as detected by CMR, was prevalent in the SSc patients without cardiac symptoms. Regional dysfunction might predict the myocardial abnormalities observed in SSc patients without cardiac symptoms. PMID- 26831017 TI - Malignant Peripheral Nerve Sheath Tumor of the Liver. AB - Malignant peripheral nerve sheath tumor (MPNST) of the liver is rare. Most cases of MPNST are accompanied by neurofibromatosis 1 (NF-1, von Recklinghausen's disease). We herein report an autopsy case of MPNST without NF-1 and review the pertinent literature. The tumor occupied the entire lobe of the liver, and was 18 cm in maximum diameter. The tumor revealed necrosis and cystic changes with hemorrhage and it had also metastasized to the peritoneum. Microscopically, the tumor was composed of pleomorphic spindle cells with hyperchromatic nuclei and mitogenic figures. The spindle cells stained positive for both S-100 and vimentin antibodies. PMID- 26831018 TI - Postcardiac Injury Syndrome Following Acute Myocardial Infarction Related to Blunt Chest Trauma. AB - Blunt chest trauma can cause acute myocardial infarction, which may also be associated with pericarditis. However, such cases are rare. We herein report a case of a 57-year-old man suffering from acute myocardial infarction due to a blunt chest trauma and postcardiac injury syndrome after discharge with spontaneous resolution of a total coronary occlusion. PMID- 26831019 TI - First Case Report of the Antemortem Diagnosis of Nonbacterial Thrombotic Endocarditis of a Mechanical Prosthetic Valve. AB - A 67-year-old man with a history of aortic mechanical valve replacement exhibited an abnormal mass on the sewing ring of the prosthesis on echocardiography. Despite receiving strong anticoagulation, he developed acute cerebral infarction due to the formation of emboli resulting from the thrombus and underwent urgent re-aortic valve replacement. Based on the microscopic findings of the resected mass, he was finally diagnosed as having nonbacterial thrombotic endocarditis (NBTE) of the mechanical prosthetic valve, which was thought to be associated with colorectal cancer. We herein report the first known case of an antemortem diagnosis of NBTE on a mechanical heart valve. PMID- 26831020 TI - Multigenerational Inheritance of Long QT Syndrome Type 2 in a Japanese Family. AB - Congenital long QT syndrome (LQTS) is an important cause of sudden cardiac death in young people without any other structural disease. Mutations in the genes encoding the cardiac ion channels or associated proteins have been shown to result in ion channel dysfunction and thereby causing LQTS. We investigated a Japanese family with LQTS for four generations, with the female family members showing severe symptoms. We performed genetic tests for LQTS-related genes and identified a heterozygous KCNH2 mutation (p.K638del). In the family, the KCNH2 mutation had a very high multigenerational inheritance, and female genotype positives showed more severe phenotypes. PMID- 26831021 TI - Bence-Jones Protein lambda-type Multiple Myeloma Patient Withdrawn from Maintenance Hemodialysis after Long-term Bortezomib and Dexamethasone Therapy. AB - The effectiveness of bortezomib treatment for multiple myeloma (MM) is well established. However, the protocol by which maintenance therapy using bortezomib should be continued for myeloma patients requiring regular hemodialysis remains to be established. We herein report a case of MM with severe renal insufficiency requiring hemodialysis for nearly 30 months which was finally withdrawn from renal replacement therapy during monthly maintenance treatment with bortezomib and dexamethasone for two years. The details of this case are essential for establishing clinical guidelines for applying intermittent low-frequency bortezomib therapy in dialysis-dependent myeloma patients. PMID- 26831022 TI - Long-Term Success with Adhesiolysis in Post-Transplant Encapsulating Peritoneal Sclerosis: A Retrospective Case Series of 4 Patients and Review of the Literature. AB - Encapsulating peritoneal sclerosis (EPS) is an occasional and serious complication for peritoneal dialysis (PD) patients for whom no evidence-based management strategies have yet been established. Encapsulating peritoneal sclerosis could appear after kidney transplantation in patients who previously underwent long-term PD. In this report, we present our experience in four PD patients diagnosed with EPS after kidney transplantation. Adhesiolysis provided improvement in their acute clinical conditions and allograft functions, despite the long-term follow-up. Surgical intervention may be a safe modality for this specific group of patients. PMID- 26831023 TI - Coexistence of Autoantibodies against the Golgi Complex and Ro52 Antigen in a Patient with Nonspecific Interstitial Pneumonia. AB - Nonspecific interstitial pneumonia (NSIP) is often associated with connective tissue diseases (CTD). The diagnosis of NSIP was confirmed in a 63-year-old man by high-resolution computed tomography and an open lung biopsy. Anti-Golgi complex autoantibodies (AGA) and anti-Ro52 antibodies were simultaneously detected at high concentrations. Autoantibodies to aminoacyl-tRNA synthetases (ARS) were negative. The patient was treated with corticosteroids for six months. During the seven-year follow-up, NSIP had a slow progression and patient had not developed the clinical features of CTD. The present study potentially demonstrates that the autoimmune process elicited by AGA and/or Ro/SSA may play a role in promoting idiopathic NSIP independently of the typical ARS routes, which has not been reported thus far. PMID- 26831024 TI - Familial Summer-type Hypersensitivity Pneumonitis: A Review of 25 Families and 50 Cases in Japan. AB - Summer-type hypersensitivity pneumonitis (SHP) is the most common form of pneumonitis in Japan; it accounts for 74% of all cases. It has been reported that 19.5-23.8% of SHP cases occur in families who live in the same house. We present our SHP cases and review 50 familial cases in 23 families that were reported in Japan (including our own) and 48 cases that were previously described in 22 articles published between January 1982 and October 2011. To the best of the authors' knowledge, this is the first review article in English to document the familial occurrence of SHP in Japan. PMID- 26831025 TI - A Newly Characterized Hemoglobin Variant with a High Oxygen Affinity, Hb Fuchu II, Presenting with Acute Myocardial Infarction. AB - A 65-year-old Japanese man presented with acute myocardial infarction (AMI) and polycythemia. Biochemical studies of the patient's hemoglobin (Hb) and the sequencing of his globin genes revealed that the polycythemia was secondary to a high oxygen affinity Hb variant, Hb Fuchu-II. Hb variants with high oxygen affinity can be an additional thrombotic risk factor in older patients and/or those with other risk factors. The patient was diagnosed with hemoglobinopathy after the development of AMI and exemplifies the importance of recognizing such conditions and of taking appropriate prophylactic interventions. PMID- 26831026 TI - Acute Myeloid Leukemia Complicated by Giant Cell Arteritis. AB - Giant cell arteritis (GCA), a type of systemic arteritis, is rare in Japan. We herein report a case of acute myeloid leukemia (AML) complicated by GCA that manifested during chemotherapy for AML. A 77-year-old woman with severe back pain was diagnosed with AML. She achieved complete remission with the resolution of her back pain following induction chemotherapy. However, she developed a headache and fever after consolidation chemotherapy. A diagnosis of GCA was made based on a biopsy of the temporal artery and arterial imaging. GCA should therefore be included in the differential diagnosis in AML patients complicated with a headache and fever of unknown origin. PMID- 26831027 TI - Carotid Body Tumor as a Cause of Stroke. AB - We herein report a case of a 78-year-old woman who was admitted to our hospital due to a stroke with left-sided hemiparesis. Ultrasound of the carotid arteries showed a carotid body tumor on the bifurcation of the right common carotid artery, which was subsequently confirmed by a further neuroradiological investigation. Magnetic resonance imaging of the head confirmed an acute ischemic lesion located in the right periventricular region. The carotid body tumor (CBT) was surgically removed and confirmed on histopathology. Our case reveals the role of carotid ultrasound in the diagnosis of a CBT, which may be a potential cause of stroke. PMID- 26831029 TI - Early-onset Parkinson's Disease Associated with Chromosome 22q11.2 Deletion Syndrome. AB - We herein report the case of a 43-year-old man with a 4-year history of resting tremor and akinesia. His resting tremor and rigidity were more prominent on the left side. He also presented retropulsion. His symptoms responded to the administration of levodopa. The patient also had a cleft lip and palate, cavum vergae, and hypoparathyroidism. A chromosome analysis disclosed a hemizygous deletion in 22q11.2, and he was diagnosed with early-onset Parkinson's disease associated with 22q11.2 deletion syndrome. However, the patient lacked autonomic nerve dysfunction, and his cardiac uptake of (123)I-metaiodobenzylguanidine was normal, indicating an underlying pathological mechanism that differed to that of sporadic Parkinson's disease. PMID- 26831028 TI - Cardiac Sympathetic Hyperactivity in a Patient with Guillain-Barre Syndrome: An Analysis Using Cardiac [(123)I] Metaiodobenzylguanidine (MIBG) Scintigraphy. AB - A 31-year-old woman gradually developed weakness in the lower extremities and gait disturbance. Subsequently, the patient developed severe constipation and hypertension with tachycardia. Nerve conduction studies revealed demyelinating polyneuropathy. Serum anti-GQ1b IgG antibody was detected. The levels of plasma noradrenaline and dopamine and urinary noradrenaline were elevated. Cardiac [(123)I] metaiodobenzylguanidine (MIBG) scintigraphy showed a normal H/M rate at the early phase and an elevated washout rate. According to these findings, the patient was diagnosed with Guillain-Barre syndrome with cardiac sympathetic hyperactivity. During convalescence, the plasma and urine catecholamine levels fell within the reference ranges, and MIBG scintigraphy showed a decreased washout rate. PMID- 26831030 TI - A Chronic Respiratory Pasteurella multocida Infection Is Well-Controlled by Long Term Macrolide Therapy. AB - A 57-year-old woman with severe bronchiectasis frequently received antibiotics, including penicillin, for acute exacerbations due to Pasteurella multocida. Although the bacteria showed a decrease in antibiotic susceptibility, her symptoms and X-ray findings became stable, and severe exacerbations were not observed for the last few years after a low-dose erythromycin treatment was started. The development of a respiratory infection with Pasteurella multocida is relatively uncommon, but it can be controlled by immunomodulation which is associated with long-term macrolide therapy. PMID- 26831031 TI - Vertigo by Breast Cancer Metastasis 33 Years after Treatment. AB - A 76-year-old woman complained of vertigo for two years. She manifested left deafness, loss of caloric response, and right-beaten nystagmus. An imaging study revealed a tumorous lesion located from the clivus to the left temporal bone with inner ear destruction. A tumor biopsy was performed endonasally and the patient was diagnosed with adenocarcinoma mimicking breast cancer. She had undergone surgery for breast cancer 33 years previously, and the current biopsy specimen showed identical pathology. Breast cancer may metastasize to the skull base; however, metastasis 33 years after surgery is very rare. PMID- 26831032 TI - Bare Metal Stent for a Coronary Artery Aneurysm. PMID- 26831033 TI - Primary Mediastinal Amyloidosis Diagnosed by Transbronchial Needle Aspiration. PMID- 26831034 TI - Bilateral Foot Acrocyanosis in an Interferon-beta-treated MS Patient. PMID- 26831035 TI - Persistent Excessive Electrocardiogram ST-segment Elevation in a Patient with a Takotsubo Syndrome: What Could be the Cause? PMID- 26831036 TI - Persistent Excessive Electrocardiogram ST-segment Elevation in a Patient with a Takotsubo Syndrome: What Could be the Cause? PMID- 26831037 TI - Change of paradigm in thoracic radionecrosis management. AB - Classically, muscular or omental flaps are the gold standard in the management of thoracic defects following radionecrosis debridement. Their vascular supply and antibacterial property was supposed to enhance healing compared with cutaneous flaps. The evolution of reconstructive surgery allowed us to challenge this dogma. Therefore, we present five consecutive cases of thoracic radionecrosis reconstructed with cutaneous perforator flaps. In four patients, we performed a free deep inferior epigastric perforator (DIEP) flap and one patient had a thoracodorsal perforator (TDAP) flap. Median time healing was 22.6 days with satisfactory cutaneous covering and good aesthetic results. There were no flap necrosis, no donor site complications. We believe that perforator flaps are a new alternative, reliable and elegant option that questions the dogma of muscular flaps in the management of thoracic radionecrosis. PMID- 26831038 TI - Harvest date effects on aroma compounds in aged Riesling icewines. AB - BACKGROUND: Riesling icewine is an important product of the Ontario wine industry. The objective of this study was to characterize concentrations in aroma compounds in aged icewines associated with three harvest dates (H1, H2, H3) using stir bar sorptive extraction-gas chromatography-mass spectrometry and to make inferences, where appropriate, with respect to their roles in potential wine quality. RESULTS: Delaying harvest decreased concentrations of many odorants, but increased many critical odor-active compounds; e.g. 1-octen-3-ol, ethyl benzoate, ethyl octanoate, cis-rose oxide, and beta-ionone. H1 wines had higher concentrations of four aldehydes, three alcohols, nine esters, seven terpenes, gamma-nonalactone, p-vinylguaiacol, beta-damascenone, and 2-furanmethanol. However, many of these compounds, with some exceptions, have relatively high odor thresholds. Fourteen compounds were above their odor thresholds, including decanal, 1-octen-3-ol, phenylethyl alcohol, four ethyl esters, cis-rose oxide, linalool, gamma-nonalactone, p-vinylguaiacol, ethyl cinnamate, beta-damascenone, and 1,1,6-trimethyl-1,2-dihydronaphthalene. H3 wines contained higher concentrations of highly odor-active compounds, e.g. 1-octen-3-ol, cis-rose oxide, and beta-ionone. Only phenylethyl alcohol [H3 odor activity value (OAV) = 0.33 (honey, spice, rose)] and linalool [H3 OAV = 0.92 (floral, lavender)] had H3 OAVs < 1. CONCLUSIONS: Early harvest increased many esters and aliphatic compounds, but delayed harvest appeared to substantially increase concentrations of several highly odor-active compounds. (c) 2016 Society of Chemical Industry. PMID- 26831039 TI - Developing a composite index of spatial accessibility across different health care sectors: A German example. AB - The evolving lack of ambulatory care providers especially in rural areas increasingly challenges the strict separation between ambulatory and inpatient care in Germany. Some consider allowing hospitals to treat ambulatory patients to tackle potential shortages of ambulatory care in underserved areas. In this paper, we develop an integrated index of spatial accessibility covering multiple dimensions of health care. This index may contribute to the empirical evidence concerning potential risks and benefits of integrating the currently separated health care sectors. Accessibility is measured separately for each type of care based on official data at the district level. Applying an Improved Gravity Model allows us to factor in potential cross-border utilization. We combine the accessibilities for each type of care into a univariate index by adapting the concept of regional multiple deprivation measurement to allow for a limited substitutability between health care sectors. The results suggest that better health care accessibility in urban areas persists when taking a holistic view. We believe that this new index may provide an empirical basis for an inter-sectoral capacity planning. PMID- 26831040 TI - Public satisfaction with the healthcare system performance in South Korea: Universal healthcare system. AB - BACKGROUND: An awareness of the public's level of satisfaction with health professionals is becoming more important as steps are being taken to improve quality, reduce costs, and implement reform. The purpose of this study is to assess public satisfaction with the healthcare system and to examine the relationship between satisfaction and socio-demographic factors in the context of the health care environment in the Republic of Korea. METHODS: The data were obtained from 1573 adults aged 20-69 in three major areas - Seoul, Gyeonggi, and Busan - by the Ministry of Health and Welfare during June and July 2011 in South Korea. Satisfaction with the healthcare system was evaluated by using 13 items in three sections: access to care, cost of care, and quality of care. A confirmatory factor analysis (CFA) was conducted to examine the validity of satisfaction with a healthcare system performance questionnaire. A structural equation model (SEM) was estimated to assess the relative impact of demographic and socio-economic variables on satisfaction. RESULTS: The study proposed a comprehensive three factor model of healthcare system performance satisfaction. Among the three factors, the quality of care had the largest impact on satisfaction with the healthcare system, suggesting that is the most important determinant of consumers' satisfaction with their healthcare system. Regarding the relationships between public satisfaction and demographic and socio-economic variables, residence and marital status were significant predictors of the satisfaction level. CONCLUSIONS: It is important to be aware of the potential significance of background variables in determining satisfaction with the healthcare system. An understanding of the characteristics of the sample enables healthcare managers and/or policymakers to inform targeted follow-up actions. PMID- 26831042 TI - Is Passive Leg Raise an Accurate Diagnostic Method for Assessing Fluid Responsiveness in Adults? PMID- 26831041 TI - A Self-Folding Hydrogel In Vitro Model for Ductal Carcinoma. AB - A significant challenge in oncology is the need to develop in vitro models that accurately mimic the complex microenvironment within and around normal and diseased tissues. Here, we describe a self-folding approach to create curved hydrogel microstructures that more accurately mimic the geometry of ducts and acini within the mammary glands, as compared to existing three-dimensional block like models or flat dishes. The microstructures are composed of photopatterned bilayers of poly (ethylene glycol) diacrylate (PEGDA), a hydrogel widely used in tissue engineering. The PEGDA bilayers of dissimilar molecular weights spontaneously curve when released from the underlying substrate due to differential swelling ratios. The photopatterns can be altered via AutoCAD designed photomasks so that a variety of ductal and acinar mimetic structures can be mass-produced. In addition, by co-polymerizing methacrylated gelatin (methagel) with PEGDA, microstructures with increased cell adherence are synthesized. Biocompatibility and versatility of our approach is highlighted by culturing either SUM159 cells, which were seeded postfabrication, or MDA-MB-231 cells, which were encapsulated in hydrogels; cell viability is verified over 9 and 15 days, respectively. We believe that self-folding processes and associated tubular, curved, and folded constructs like the ones demonstrated here can facilitate the design of more accurate in vitro models for investigating ductal carcinoma. PMID- 26831043 TI - Observed Benefits to On-site Medical Services during an Annual 5-day Electronic Dance Music Event with Harm Reduction Services. AB - BACKGROUND: With increasing attendance and media attention, large-scale electronic dance music events (EDMEs) are a subset of mass gatherings that have a unique risk profile for attendees and promoters. Shambhala Music Festival (Canada) is a multi-day event in a rural setting with a recognized history of providing harm reduction (HR) services alongside medical care. Study/Objective This manuscript describes the medical response at a multi-day electronic music festival where on-site HR interventions and dedicated medical care are delivered as parallel public health measures. METHODS: This study was a descriptive case report. Medical encounters and event-related data were documented prospectively using an established event registry database. RESULTS: In 2014, Shambhala Music Festival had 67,120 cumulative attendees over a 7-day period, with a peak daily attendance of 15,380 people. There were 1,393 patient encounters and the patient presentation rate (PPR) was 20.8 per one thousand. The majority of these (90.9%) were for non-urgent complaints. The ambulance transfer rate (ATR) was 0.194 per one thousand and 0.93% of patient encounters were transferred by ambulance. No patients required intubation and there were no fatalities. Harm reduction services included mobile outreach teams, distribution of educational materials, pill checking facilities, a dedicated women's space, and a "Sanctuary" area that provided non-medical peer support for overwhelmed guests. More than 10,000 encounters were recorded by mobile and booth-based preventive and educational services, and 2,786 pills were checked on-site with a seven percent discard rate. CONCLUSION: Dedicated medical and HR services represent two complementary public health strategies to minimize risk at a multi-day electronic music festival. The specific extent to which HR strategies reduce the need for medical care is not well understood. Incorporation of HR practices when planning on-site medical care has the potential to inform patient management, reduce presentation rates and acuity, and decrease utilization and cost for local, community-based health services. PMID- 26831044 TI - Increased serum microRNAs are closely associated with the presence of microvascular complications in type 2 diabetes mellitus. AB - Circulating microRNAs (miRNAs) are emerging biomarkers for type 2 diabetes mellitus (T2DM). However, a comprehensive characterization of the serum miRNA profile in patients with T2DM-associated microvascular disease (T2DMC) has rarely been reported. In this study, we obtained serum samples from 184 T2DM patients (92 with microvascular complications and 92 free of complications) and 92 age/gender-matched controls. The levels of 754 miRNAs were initially analyzed using a TaqMan Low Density Array (TLDA) in three pooled samples from 24 T2DM patients, 24 T2DMC patients and 24 controls. Markedly upregulated miRNAs in the patients' groups were subsequently validated individually by quantitative reverse transcription PCR (RT-qPCR) in the same samples used for TLDA and further confirmed in another larger cohort consisting of 68 patients with T2DM, 68 patients with T2DMC and 68 controls. Five miRNAs were significantly upregulated in T2DM patients (p < 0.05) including miR-661, miR-571, miR-770-5p, miR-892b and miR-1303. Moreover, the levels of the five miRNAs were higher in patients with complications than in those without complications. Regression analyses revealed the five miRNAs were significantly correlated with microvascular complications (p < 0.05). The five serum miRNAs identified in our study hold potential as auxiliary biomarkers and novel risk factors for T2DM-associated microvascular complications. PMID- 26831045 TI - Competition in the Dutch hospital sector: an analysis of health care volume and cost. AB - This paper evaluates the impact of market competition on health care volume and cost. At the start of 2005, the financing system of Dutch hospitals started to be gradually changed from a closed-end budgeting system to a non-regulated price competitive prospective reimbursement system. The gradual implementation of price competition is a 'natural experiment' that provides a unique opportunity to analyze the effects of market competition on hospital behavior. We have access to a unique database, which contains hospital discharge data of diagnosis treatment combinations (DBCs) of individual patients, including detailed care activities. Difference-in-difference estimates show that the implementation of market-based competition leads to relatively lower total costs, production volume and number of activities overall. Difference-in-difference estimates on treatment level show that the average costs for outpatient DBCs decreased due to a decrease in the number of activities per DBC. The introduction of market competition led to an increase of average costs of inpatient DBCs. Since both volume and number of activities have not changed significantly, we conclude that the cost increase is likely the result of more expensive activities. A possible explanation for our finding is that hospitals look for possible efficiency improvements in predominantly outpatient care products that are relatively straightforward, using easily analyzable technologies. The effects of competition on average cost and the relative shares of inpatient and outpatient treatments on specialty level are significant but contrary for cardiology and orthopedics, suggesting that specialties react differently to competitive incentives. PMID- 26831046 TI - Safety of lumbar punctures in patients with thrombocytopenia. AB - BACKGROUND: American Association of Blood Banks guidelines recommend a minimum platelet count of 50 * 10(9) /l for LPs (lumbar puncture), but evidence is lacking. The objective of this study was to describe the range of platelet counts at which LPs are performed, and the rate of traumatic taps and haemorrhagic complications in an adult oncology population. METHODS: A retrospective cohort study of patients receiving LPs over a 2-year period was carried out. Bleeding risk factors captured included anticoagulants, antiplatelets, end-stage renal disease, and other bleeding disorders. Pre-LP platelet counts were those collected <=24 h from the time of the LP. Traumatic tap was defined as 500 or more red blood cells per high-power field in cerebrospinal fluid. RESULTS: One hundred and thirty-five patients underwent 369 LPs. Twenty-eight (7.6%) LPs were performed at a platelet count <= 50 * 10(9) /l; 18 patients received a platelet transfusion prior to the LP, with post-transfusion count available prior to LP in only one patient. Traumatic taps occurred in 16 of 113 (14.2%) LPs in patients with thrombocytopenia (platelet count < 150 * 10(9) /l) compared to 27 of 242 (11.1%) LPs in patients with a normal platelet count (P = 0.48). The presence of bleeding risk factors did not increase the incidence of traumatic taps. There were no haemorrhagic complications. CONCLUSIONS: Among this cohort of adult oncology patients, there were no haemorrhagic complications. Traumatic taps were not increased in patients with thrombocytopenia. The effects of platelet transfusions were rarely assessed prior to LP. Further studies should be pursued to assess whether platelet count thresholds lower than 50 * 10(9) /l are safe for lumbar puncture. PMID- 26831047 TI - Risk of exacerbations in COPD and asthma patients living in the neighbourhood of livestock farms: Observational study using longitudinal data. AB - OBJECTIVE: Living in an area with a high density of livestock farms has been associated with adverse respiratory health effects in some studies. As patients with COPD and asthma already have a compromised respiratory function and chronic airway inflammation, they are expected to be at increased risk for adverse respiratory health effects. The objective of this study was to assess the association between livestock exposure and exacerbations in COPD and asthma. METHODS: 899 COPD and 2546 asthma patients from 15 general practices in a rural area with a high livestock density and 933 COPD and 2310 asthma patients from 15 practices in a control area in the Netherlands were included. Occurrence of exacerbations was based on the pharmaceutical treatment of exacerbations in COPD and asthma patients using 2006-2012 prescription data of electronic medical records. Farm exposure was assessed by comparing the study area with the control area, and with individual exposure estimates in the study area using Geographic Information System data. RESULTS: The exacerbation rate was higher in the study area compared with the control area in COPD (IRR: 1.28; 95%CI: 1.06-1.55), but not in asthma patients (IRR: 0.87; 95%CI: 0.72-1.05). In general, individual exposure estimates in the study area were not associated with exacerbations. COPD patients living within a 500m radius of up to12,499 chickens had a 36% higher exacerbation rate (IRR: 1.36; 95%CI: 1.03-1.79). CONCLUSIONS: Living in an area with a high livestock density is a risk factor for exacerbations in COPD patients. The environmental exposure responsible for this increased risk remains to be elucidated. PMID- 26831048 TI - Anesthetic Success of an Inferior Alveolar Nerve Block and Supplemental Articaine Buccal Infiltration for Molars and Premolars in Patients with Symptomatic Irreversible Pulpitis. AB - INTRODUCTION: The purpose of this retrospective study was to determine the anesthetic success of the inferior alveolar nerve (IAN) block, and supplemental articaine buccal infiltration after a failed IAN block, in first and second molars and premolars in patients presenting with symptomatic irreversible pulpitis. METHODS: As part of 6 studies, 375 emergency patients presenting with symptomatic irreversible pulpitis received 2% lidocaine with 1:100,000 epinephrine via an IAN block. After profound lip numbness, endodontic access and instrumentation were initiated. If the patient felt moderate to severe pain, a supplemental buccal infiltration of a cartridge of 4% articaine with 1:100,000 epinephrine was administered (204 patients), and endodontic treatment continued. Success was defined as the ability to access and instrument the tooth without pain (visual analogue scale rating of 0) or mild pain (visual analogue scale rating less than or equal to 54 mm). RESULTS: IAN block success was 28% for the first molars, 25% for the second molars, and 39% for the premolars. There were no significant differences when comparing molars with premolars. For the supplemental articaine buccal infiltration, success was 42% for the first molars, 48% for the second molars, and 73% for the premolars. There were no significant differences when comparing the molars, but there was a significant difference when comparing the premolars with the molars. CONCLUSIONS: For patients presenting with symptomatic irreversible pulpitis, the success rates for the IAN block and supplemental buccal infiltration of articaine of the molars and premolars would not be high enough to ensure profound pulpal anesthesia. PMID- 26831049 TI - Complex Apical Intraradicular Infection and Extraradicular Mineralized Biofilms as the Cause of Wet Canals and Treatment Failure: Report of 2 Cases. AB - This article describes 2 cases that showed persistent intracanal exudation (wet canal) even after several visits of antimicrobial endodontic treatment. Histologic and histobacteriologic investigation was conducted for determination of the cause. The 2 cases involved teeth with apical periodontitis lesions, which presented persistent exudation refractory to treatment after several visits. In case 1, it was not possible to achieve a dry canal, and surgery had to be performed. In case 2, attempts to dry the canal succeeded and the canal was filled, but follow-up examination showed an enlarged apical periodontitis lesion and extraction was performed. Biopsy specimens consisting of the root apex and apical periodontitis lesion for case 1 and the whole root for case 2 were subjected to histologic and histobacteriologic analyses. Both cases showed complex bacterial infection in the apical root, affecting both the intraradicular space and the outer root surface. Case 1 showed bacterial biofilms in ramifications, on untouched walls, and extending to the external root surface to form a thick and partially mineralized structure with high bacterial density. Different bacterial morphotypes were evidenced. Case 2 had a ledge on the apical canal wall created during instrumentation, which was filled with necrotic debris, filling material, and bacteria. The walls of the apical portion of the canal were covered by a bacterial biofilm, which was continuous with a thick extraradicular biofilm covering the cementum and dentin in resorptive defects. The extraradicular biofilm showed areas of mineralization and was dominated by filamentous bacteria. The 2 cases with wet canals and treatment failure were associated with complex persistent infection in the apical part of the root canal system extending to form thick and partially mineralized biofilm structures (calculus) on the outer apical root surface. PMID- 26831050 TI - Evaluation of Time to Fracture and Vertical Forces Applied by a Novel Gentlefile System for Root Canal Preparation in Simulated Root Canals. AB - INTRODUCTION: A great number of studies performed in the last 3 decades have shown the superior mechanical features of nickel-titanium files as compared with stainless steel files. A novel file system recently developed, Gentlefile, defies these findings and claims to have superior qualities despite the fact it is made from stainless steel. METHODS: Three file systems were used in this experiment: ProTaper Next (X1, X2, and X3), RevoS (SC2, SC3, and AS30), and Gentlefile (GF1, GF2, and GF3). Time to fracture, rotations to fracture, and vertical forces applied to a simulated root canal, which was fabricated from a metal block with a Plexiglas cover, were measured. RESULTS: The GF system required significantly longer time and more rotations to fracture compared with the ProTaper and RevoS systems (P < .001). The GF system applied significantly less vertical force to the canal in comparison with the ProTaper and RevoS systems (P < .01). CONCLUSIONS: Under the limitations of this study the GF system showed better mechanical properties in comparison with the ProTaper and RevoS systems. Further investigation is needed to assess the clinical meaning of these findings. PMID- 26831051 TI - Pathophysiologic Insights into Heart Rate Reduction in Heart Failure: Implications in the Use of Beta-Blockers and Ivabradine. AB - OPINION STATEMENT: In patients with heart failure, an elevated heart rate is associated with worse cardiovascular outcomes and is increasingly recognized as a modifiable risk factor. Beta-blockers are the mainstay of therapy for heart failure. However, up-titration of beta-blockers in response to persistently elevated heart rate can be associated with increased risk of adverse reactions besides negative chronotropism. Recently, the specific heart rate-lowering agent, ivabradine, which acts by directly and selectively inhibiting the I f current in the sinoatrial node, generated renewed interest in potential benefits of pharmacologic modification of heart rate in heart failure. Several placebo controlled, multicenter clinical trials showed the benefits of ivabradine in patients with angina and heart failure, which is largely confined to those with left ventricular systolic dysfunction. In addition, the other potential effects of ivabradine have been proposed. PMID- 26831052 TI - Health-related quality of life among Indigenous Australians diagnosed with cancer. AB - PURPOSE: Health-related quality of life (HRQoL) and associated factors were assessed among 155 Indigenous Australian adult cancer patients 6 months post diagnosis. METHODS: The Assessment of Quality of Life-4D Questionnaire was used to assess HRQoL. Differences in the median utility score among subgroups of interest were examined using nonparametric tests. Factors associated with excellent HRQoL were assessed through logistic regression. RESULTS: Participants' mean age was 52 years (range 20-78), and the majority were female (60 %), unemployed (72 %), and recruited from outpatients clinics (64 %). Breast cancer (27 %) was the most common diagnosis. The median HRQoL score was 0.62; 14 % of participants reported excellent HRQoL (>0.90). After adjusting for age, admission status, and treatment, excellent HRQoL was more likely among participants of Torres Strait Islander origin [adjusted odds ratio (AOR) 3.68; 95 % CI 1.23 11.01], those living in regional areas (AOR 5.59; 95 % CI 1.42-22.06), and those whose main language spoken at home was not English (AOR 3.60; 95 % CI 1.08-11.99) and less likely among those reporting less contact with Indigenous people (AOR 0.23; 95 % CI 0.68-0.81). CONCLUSION: Assessing HRQoL is important to identifying and improving the length and quality of cancer survivorship, especially in groups that have significantly poorer cancer outcomes, such as Indigenous Australians. Acknowledging the study's observational nature, we found HRQoL was lower than reported for other Australians, and we identified some socio-demographic factors that were associated with excellent HRQoL. Such assessments are an important component of identifying and evaluating appropriate interventions to improve the health and well-being of Indigenous cancer patients. PMID- 26831053 TI - A synthesis of meta-analytic evidence of behavioral interventions to reduce HIV/STIs. AB - To identify the mode of delivery, communicator, and content dimensions that make STI/HIV prevention interventions most successful at increasing condom use/protected sex or reducing STI/HIV incidence. A literature search for published meta-analyses of STI/HIV prevention interventions yielded 37 meta analyses that had statistically tested the moderating effects of the dimensions. Significant and non-significant moderators from the coded dimensions were extracted from each meta-analysis. The most consistently significant moderators included matching the gender or ethnicity of the communicator to the intervention recipients, group targeting or tailoring of the intervention, use of a theory to underpin intervention design, providing factual information, presenting arguments designed to change attitudes, and providing condom skills and intrapersonal skills training. The absence of significant effects for intervention duration and expert delivery are also notable. The success of HIV/STI prevention interventions may be enhanced not only by providing skills training and information designed to change attitudes, but also by ensuring that the content is tailored to the target group and delivered by individuals of the same gender and ethnicity as the recipients. PMID- 26831054 TI - Case Files of the University of Massachusetts Toxicology Fellowship: Does This Smoke Inhalation Victim Require Treatment with Cyanide Antidote? AB - Cyanide toxicity is common after significant smoke inhalation. Two cases are presented that provide framework for the discussion of epidemiology, pathogenesis, presenting signs and symptoms, and treatment options of inhalational cyanide poisoning. An evidence-based algorithm is proposed that utilizes point-of-care testing to help physicians identify patients who benefit most from antidotal therapy. PMID- 26831055 TI - [Active surveillance for low-risk prostate cancer]. AB - Autopsy studies have confirmed the high prevalence of latent prostate cancer; however, only a certain portion of patients require definite treatment. Active surveillance is one of the treatment options which, according to national and international guidelines, should be offered to patients with newly diagnosed low risk prostate cancer. Prostate cancer-specific survival is high in these patients; therefore, curative treatment, such as radical prostatectomy, external beam radiotherapy and brachytherapy may be initially deferred in order to avoid therapy-related side effects. In order to qualify for active surveillance, strict inclusion criteria have to be met; nevertheless, the reliable identification of low-risk prostate cancer patients is not always possible. Patients under active surveillance are followed up regularly with prostate-specific antigen (PSA) testing, digital rectal examination (DRE) and repeat prostate biopsies. Due to the heterogeneity of primary prostate tumors precise molecular diagnostic techniques could allow individualized treatment strategies in the future. PMID- 26831056 TI - Relationship of hepatic steatosis severity and coronary artery disease characteristics assessed by coronary CT angiography. AB - The objective of this study was to investigate the relationship between the severity of hepatic steatosis and coronary artery disease characteristics assessed by coronary computed tomography (CT) angiography. This retrospective analysis consisted of 2028 patients. Hepatic steatosis was evaluated by liver attenuation on unenhanced CT and the patients were divided into four groups (>=60 HU, 54-59 HU, 43-53 HU, <=42 HU). Coronary calcification was calculated using the Agatston method. Obstructive disease was defined as >=50 % stenosis assessed by CT. A high-risk plaque was defined by a remodeling index >1.1 and low attenuation (<30 HU). Patients with a segment involvement score >4 were determined to have extensive disease. Logistic regression analysis was performed to study multivariate associations. Severity of hepatic steatosis was associated with coronary calcification (p = 0.02), obstructive disease (p < 0.0001), presence of a high-risk plaque (p = 0.0001) and extensive disease (p = 0.001) in the univariate analysis. However, the relationships were attenuated in the multivariate analysis with the exception of obstructive disease (p = 0.04). Liver attenuation of <54 HU was significantly associated with obstructive coronary artery disease independent of conventional risk factors such as age, sex, diabetes mellitus, hypertension, dyslipidemia and smoking (hepatic attenuation 43 53 HU, odds ratio 1.52, 95 % confidence interval 1.11-2.10, p = 0.01; <=42 HU, odds ratio 1.65, 95 % confidence interval 1.10-2.45, p = 0.02). Although conventional risk factors were stronger predictors of coronary calcification and plaque formation, the severity of hepatic steatosis remained an independent risk factor for obstructive coronary artery disease. Coronary CT angiography may play a potential role in risk stratification for patients with hepatic steatosis. PMID- 26831057 TI - Detecting cardiac involvement with magnetic resonance in patients with active eosinophilic granulomatosis with polyangiitis. AB - Cardiac involvement is the most important prognostic factor in eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). The aims of this study were to describe findings of cardiac magnetic resonance (CMR) in patients with active EGPA and to find factors associated with cardiac involvement detected by CMR that could help identify patients who would benefit from the examination. Medical records and CMR images in 16 consecutive EGPA patients (8 women and 8 men, median age of 47 years ranging from 34 to 68 years) were reviewed. Clinical features and results of laboratory tests were compared according to the presence of myocardial late gadolinium enhancement (LGE) on CMR images. The patients were followed for the development of cardiac symptoms and signs (mean follow up duration, 40.5 +/- 12.8 months). Among the total of 16 patients, 8 (50 %) had myocardial LGE according to CMR, located in the subendocardial layer in 7 of them (87.5 %). The extent of LGE had a significant negative correlation with left ventricular ejection fraction (LVEF, rho = -0.723, p = 0.043). The presence of LGE was associated with larger end-systolic left ventricle internal dimension (34 vs. 28 mm, p = 0.027) and presence of diastolic dysfunction (75 vs. 0 %, p = 0.008) on echocardiography, elevated NT-proBNP (75 vs. 12.5 %, p = 0.012), and elevated CK-MB (62.5 vs. 0 %, p = 0.010) compared to the group without LGE. Only one patient (6.3 %) had cardiac symptoms before CMR and another patient (6.3 %) developed heart failure 4 years later during remission. The other 14 patients remained free from cardiac signs and symptoms during the follow-up period. In patients with active EGPA, CMR enables detection of cardiac involvement when cardiac symptoms are not present. Echocardiographic diastolic dysfunction and elevated NT-proBNP or CK-MB may help identify active EGPA patients who can benefit from CMR to detect cardiac involvement without cardiac symptoms. PMID- 26831058 TI - Ileocecal Intussusception Caused by an Appendiceal Neoplasm. AB - Mucinous appendiceal neoplasm occurs in less than 1% of appendicectomies. Majority of what is known in the literature is about pseudomyxoma peritonei, which exists as its disseminated form. Pictorial imagery of its pre-disseminated form is rarely observed. We present in a case report form a case of low-grade mucinous neoplasm of the appendix resulting in focal intussusception including images captured from this unique case that will become a learning case for readers of the journal. PMID- 26831059 TI - Dynamic Change of Total Bilirubin after Portal Vein Embolization is Predictive of Major Complications and Posthepatectomy Mortality in Patients with Hilar Cholangiocarcinoma. AB - OBJECTIVES: This study aims to evaluate the role of dynamic change in total bilirubin after portal vein embolization (PVE) in predicting major complications and 30-day mortality in patients with hilar cholangiocarcinoma (HCCA). METHODS: Retrospective analysis of prospectively maintained data of 64 HCCA patients who underwent PVE before hepatectomy in our institution was used. Total bilirubin and other parameters were measured daily in peri-PVE period. The difference between them and the baseline value from days 0-5 to day -1 (?D1) and days 5-14 to day -1 (?D2) were calculated. The relationship between ?D1 and ?D2 of total bilirubin and major complications as well as 30-day mortality was analyzed. RESULTS: Out of 64 patients, 10 developed major complications (15.6 %) and 6 patients (9.3 %) had died within 30 days after surgery. The ?D2 of total bilirubin after PVE was most significantly associated with major complications (P < 0.001) and 30-day mortality (P = 0.002). In addition, it was found to be an independent predictor of major complications after PVE (odds ratio (OR) = 1.050; 95 % CI 1.017-1.084). ASA >3 (OR = 12.048; 95 % CI 1.019-143.321), ?D2 of total bilirubin (OR = 1.058; 95 % CI 1.007-1.112), and ?D2 of prealbumin (OR = 0.975; 95 % CI 0.952-0.999) were associated with higher risk of 30-day mortality after PVE. Receiver operating characteristic curves showed that ?D2 of total bilirubin were better predictors than ?D1 for major complications (AUC (?D2) 0.817; P = 0.002 vs. AUC (?D1) 0.769; P = 0.007) and 30-day mortality (ACU(?D2) 0.868; P = 0.003 vs. AUC(?D1) 0.721;P = 0.076). CONCLUSION: Patients with increased total bilirubin in 5-14 days after PVE may indicate a higher risk of major complications and 30-day mortality if the major hepatectomy were performed. PMID- 26831060 TI - Assessment of the Double-Staple Technique for Esophagoenteric Anastomosis in Gastric Cancer. AB - INTRODUCTION: Reports on outcomes after double-staple technique (DST) for total and proximal gastrectomy are limited, originating mostly from Asian centers. Our objective was to examine anastomotic leak and stricture with DST for esophagoenteric anastomosis in gastric cancer patients. METHODS: A single institution review was performed for patients who underwent total/proximal gastrectomy with DST between 2006 and 2015. DST was performed using transoral anvil delivery (OrVil) with end-to-end anastomosis. Clinical characteristics and outcomes, including anastomotic leak and stricture, were recorded. RESULTS: Overall, DST was performed in 60 patients [total gastrectomy (81.7%, n = 49/60), proximal gastrectomy (10.0%, n = 6/60), and completion gastrectomy (8.3%, n = 5/60)]. Neoadjuvant chemotherapy was administered to 21 patients (35.0%), and 6 patients (10.0%) received external beam radiation therapy prior to completion gastrectomy. Operative approach was open (51.7%, n = 31/60), laparoscopic (43.3%, n = 26/60), or robotic (5.0%, n = 3/60). Anastomotic leak occurred in 6.7% (n = 4/60), while stricture independent of leak was identified in 19.0% (n = 11/58) of patients. Complications occurred in 38.3% (n = 23/60) of patients, of which 52% were classified as Clavien-Dindo grades III-V complications. CONCLUSION: In the largest Western series of DST for esophagoenteric anastomoses in gastric cancer surgery, our experience demonstrates that DST is safe and effective with low rates of leak and stricture. PMID- 26831061 TI - Current Status of Minimally Invasive Surgery for Rectal Cancer. AB - Recent randomized controlled data have shown possible limitations to laparoscopic treatment of rectal cancer. The retrospective data, used as the basis for designing the trials, and which showed no problems with the technique, are discussed. The design of the randomized trials is discussed relative to the future meta-analysis of the recent data. The implications of the current findings on practice are discussed as surgeons try to adjust their practice to the new findings. The possible next steps for clinical and research innovations are put into perspective as new technology is considered to compensate for newly identified limitations in the laparoscopic treatment of rectal cancer. PMID- 26831063 TI - Correction for Giuggioli et al., Stigmergy, collective actions, and animal social spacing. PMID- 26831062 TI - Cardia and Non-Cardia Gastric Cancer Have Similar Stage-for-Stage Prognoses After R0 Resection: a Large-Scale, Multicenter Study in China. AB - Although the clinicopathological features of cardia gastric cancer (GC) differ from those of non-cardia GC, it is unclear whether the former has poorer prognosis than the latter. The aim of this study was to compare clinicopathological characteristics and prognosis between cardia and non-cardia GC. From December 2009 to December 2011, 1633 patients who had undergone R0 resection of GC at four Chinese centers were enrolled in this study. Their clinicopathological features and survival outcomes were evaluated. Compared with non-cardia GC, cardia GC was associated with a significantly higher proportion of male patients, older age, more advanced pathological stage, and less-favorable clinicopathological features at diagnosis. The 5-year survival rate was significantly lower in the cardia GC group than in the non-cardia GC group. However, no significant difference in overall survival (OS) was observed between the two groups at any pathological TNM stage. Pathological stage was confirmed as an independent prognostic factor of OS. More advanced disease represents most of the cases in this Chinese population. Compared with patients with non-cardia GC, patients with cardia GC were diagnosed at a more advanced stage and had worse prognosis after undergoing R0 resection. However, cardia and non-cardia GCs have similar stage-for-stage prognoses. PMID- 26831064 TI - CHK2-BRCA1 tumor-suppressor axis restrains oncogenic Aurora-A kinase to ensure proper mitotic microtubule assembly. AB - BRCA1 (breast cancer type 1 susceptibility protein) is a multifunctional tumor suppressor involved in DNA damage response, DNA repair, chromatin regulation, and mitotic chromosome segregation. Although the nuclear functions of BRCA1 have been investigated in detail, its role during mitosis is little understood. It is clear, however, that loss of BRCA1 in human cancer cells leads to chromosomal instability (CIN), which is defined as a perpetual gain or loss of whole chromosomes during mitosis. Moreover, our recent work has revealed that the mitotic function of BRCA1 depends on its phosphorylation by the tumor-suppressor kinase Chk2 (checkpoint kinase 2) and that this regulation is required to ensure normal microtubule plus end assembly rates within mitotic spindles. Intriguingly, loss of the positive regulation of BRCA1 leads to increased oncogenic Aurora-A activity, which acts as a mediator for abnormal mitotic microtubule assembly resulting in chromosome missegregation and CIN. However, how the CHK2-BRCA1 tumor suppressor axis restrains oncogenic Aurora-A during mitosis to ensure karyotype stability remained an open question. Here we uncover a dual molecular mechanism by which the CHK2-BRCA1 axis restrains oncogenic Aurora-A activity during mitosis and identify BRCA1 itself as a target for Aurora-A relevant for CIN. In fact, Chk2-mediated phosphorylation of BRCA1 is required to recruit the PP6C-SAPS3 phosphatase, which acts as a T-loop phosphatase inhibiting Aurora-A bound to BRCA1. Consequently, loss of CHK2 or PP6C-SAPS3 promotes Aurora-A activity associated with BRCA1 in mitosis. Aurora-A, in turn, then phosphorylates BRCA1 itself, thereby inhibiting the mitotic function of BRCA1 and promoting mitotic microtubule assembly, chromosome missegregation, and CIN. PMID- 26831065 TI - Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD. AB - Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. Aberrant platelet-derived growth factor receptor beta (PDGFRbeta) signaling in cancer has motivated the development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib. The discovery of a novel ligand for PDGFRbeta, platelet-derived growth factor (PDGF)-DD, opened the possibility of a previously unidentified signaling pathway involved in tumor development. However, the precise function of PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly, ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous malignant cell clones, some of which expressed PDGFRbeta. The presence of a subclonal population of tumor cells characterized by PDGFRbeta expression was further validated in a cohort of human PanNET. In conclusion, we demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the PDGF-DD/PDGFRbeta axis. PMID- 26831066 TI - Role of growth hormone-releasing hormone in dyslipidemia associated with experimental type 1 diabetes. AB - Dyslipidemia associated with triglyceride-rich lipoproteins (TRLs) represents an important residual risk factor for cardiovascular and chronic kidney disease in patients with type 1 diabetes (T1D). Levels of growth hormone (GH) are elevated in T1D, which aggravates both hyperglycemia and dyslipidemia. The hypothalamic growth hormone-releasing hormone (GHRH) regulates the release of GH by the pituitary but also exerts separate actions on peripheral GHRH receptors, the functional role of which remains elusive in T1D. In a rat model of streptozotocin (STZ)-induced T1D, GHRH receptor expression was found to be up-regulated in the distal small intestine, a tissue involved in chylomicron synthesis. Treatment of T1D rats with a GHRH antagonist, MIA-602, at a dose that did not affect plasma GH levels, significantly reduced TRL, as well as markers of renal injury, and improved endothelial-dependent vasorelaxation. Glucagon-like peptide 1 (GLP-1) reduces hyperglucagonemia and postprandial TRL, the latter in part through a decreased synthesis of apolipoprotein B-48 (ApoB-48) by intestinal cells. Although plasma GLP-1 levels were elevated in diabetic animals, this was accompanied by increased rather than reduced glucagon levels, suggesting impaired GLP-1 signaling. Treatment with MIA-602 normalized GLP-1 and glucagon to control levels in T1D rats. MIA-602 also decreased secretion of ApoB-48 from rat intestinal epithelial cells in response to oleic acid stimulation in vitro, in part through a GLP-1-dependent mechanism. Our findings support the hypothesis that antagonizing the signaling of GHRH in T1D may improve GLP-1 function in the small intestine, which, in turn, diminishes TRL and reduces renal and vascular complications. PMID- 26831067 TI - Decision-related perturbations of decision-irrelevant eye movements. AB - It is well established that ongoing cognitive functions affect the trajectories of limb movements mediated by corticospinal circuits, suggesting an interaction between cognition and motor action. Although there are also many demonstrations that decision formation is reflected in the ongoing neural activity in oculomotor brain circuits, it is not known whether the decision-related activity in those oculomotor structures interacts with eye movements that are decision irrelevant. Here we tested for an interaction between decisions and instructed saccades unrelated to the perceptual decision. Observers performed a direction discrimination decision-making task, but made decision-irrelevant saccades before registering their motion decision with a button press. Probing the oculomotor circuits with these decision-irrelevant saccades during decision making revealed that saccade reaction times and peak velocities were influenced in proportion to motion strength, and depended on the directional congruence between decisions about visual motion and decision-irrelevant saccades. These interactions disappeared when observers passively viewed the motion stimulus but still made the same instructed saccades, and when manual reaction times were measured instead of saccade reaction times, confirming that these interactions result from decision formation as opposed to visual stimulation, and are specific to the oculomotor system. Our results demonstrate that oculomotor function can be affected by decision formation, even when decisions are communicated without eye movements, and that this interaction has a directionally specific component. These results not only imply a continuous and interactive mixture of motor and decision signals in oculomotor structures, but also suggest nonmotor recruitment of oculomotor machinery in decision making. PMID- 26831069 TI - Streamlined discovery of cross-linked chromatin complexes and associated histone modifications by mass spectrometry. AB - Posttranslational modifications (PTMs) are key contributors to chromatin function. The ability to comprehensively link specific histone PTMs with specific chromatin factors would be an important advance in understanding the functions and genomic targeting mechanisms of those factors. We recently introduced a cross linked affinity technique, BioTAP-XL, to identify chromatin-bound protein interactions that can be difficult to capture with native affinity techniques. However, BioTAP-XL was not strictly compatible with similarly comprehensive analyses of associated histone PTMs. Here we advance BioTAP-XL by demonstrating the ability to quantify histone PTMs linked to specific chromatin factors in parallel with the ability to identify nonhistone binding partners. Furthermore we demonstrate that the initially published quantity of starting material can be scaled down orders of magnitude without loss in proteomic sensitivity. We also integrate hydrophilic interaction chromatography to mitigate detergent carryover and improve liquid chromatography-mass spectrometric performance. In summary, we greatly extend the practicality of BioTAP-XL to enable comprehensive identification of protein complexes and their local chromatin environment. PMID- 26831068 TI - G protein-gated IKACh channels as therapeutic targets for treatment of sick sinus syndrome and heart block. AB - Dysfunction of pacemaker activity in the sinoatrial node (SAN) underlies "sick sinus" syndrome (SSS), a common clinical condition characterized by abnormally low heart rate (bradycardia). If untreated, SSS carries potentially life threatening symptoms, such as syncope and end-stage organ hypoperfusion. The only currently available therapy for SSS consists of electronic pacemaker implantation. Mice lacking L-type Cav1.3 Ca(2+) channels (Cav1.3(-/-)) recapitulate several symptoms of SSS in humans, including bradycardia and atrioventricular (AV) dysfunction (heart block). Here, we tested whether genetic ablation or pharmacological inhibition of the muscarinic-gated K(+) channel (IKACh) could rescue SSS and heart block in Cav1.3(-/-) mice. We found that genetic inactivation of IKACh abolished SSS symptoms in Cav1.3(-/-) mice without reducing the relative degree of heart rate regulation. Rescuing of SAN and AV dysfunction could be obtained also by pharmacological inhibition of IKACh either in Cav1.3(-/-) mice or following selective inhibition of Cav1.3-mediated L-type Ca(2+) (ICa,L) current in vivo. Ablation of IKACh prevented dysfunction of SAN pacemaker activity by allowing net inward current to flow during the diastolic depolarization phase under cholinergic activation. Our data suggest that patients affected by SSS and heart block may benefit from IKACh suppression achieved by gene therapy or selective pharmacological inhibition. PMID- 26831070 TI - Tissue nonautonomous effects of fat body methionine metabolism on imaginal disc repair in Drosophila. AB - Regulatory mechanisms for tissue repair and regeneration within damaged tissue have been extensively studied. However, the systemic regulation of tissue repair remains poorly understood. To elucidate tissue nonautonomous control of repair process, it is essential to induce local damage, independent of genetic manipulations in uninjured parts of the body. Herein, we develop a system in Drosophila for spatiotemporal tissue injury using a temperature-sensitive form of diphtheria toxin A domain driven by the Q system to study factors contributing to imaginal disc repair. Using this technique, we demonstrate that methionine metabolism in the fat body, a counterpart of mammalian liver and adipose tissue, supports the repair processes of wing discs. Local injury to wing discs decreases methionine and S-adenosylmethionine, whereas it increases S-adenosylhomocysteine in the fat body. Fat body-specific genetic manipulation of methionine metabolism results in defective disc repair but does not affect normal wing development. Our data indicate the contribution of tissue interactions to tissue repair in Drosophila, as local damage to wing discs influences fat body metabolism, and proper control of methionine metabolism in the fat body, in turn, affects wing regeneration. PMID- 26831071 TI - Charge of a quasiparticle in a superconductor. AB - Nonlinear charge transport in superconductor-insulator-superconductor (SIS) Josephson junctions has a unique signature in the shuttled charge quantum between the two superconductors. In the zero-bias limit Cooper pairs, each with twice the electron charge, carry the Josephson current. An applied bias VSD leads to multiple Andreev reflections (MAR), which in the limit of weak tunneling probability should lead to integer multiples of the electron charge ne traversing the junction, with n integer larger than 2Delta/eVSD and Delta the superconducting order parameter. Exceptionally, just above the gap eVSD >= 2Delta, with Andreev reflections suppressed, one would expect the current to be carried by partitioned quasiparticles, each with energy-dependent charge, being a superposition of an electron and a hole. Using shot-noise measurements in an SIS junction induced in an InAs nanowire (with noise proportional to the partitioned charge), we first observed quantization of the partitioned charge q = e*/e = n, with n = 1-4, thus reaffirming the validity of our charge interpretation. Concentrating next on the bias region eVSD ~ 2Delta, we found a reproducible and clear dip in the extracted charge to q ~ 0.6, which, after excluding other possibilities, we attribute to the partitioned quasiparticle charge. Such dip is supported by numerical simulations of our SIS structure. PMID- 26831072 TI - Oyster reproduction is affected by exposure to polystyrene microplastics. AB - Plastics are persistent synthetic polymers that accumulate as waste in the marine environment. Microplastic (MP) particles are derived from the breakdown of larger debris or can enter the environment as microscopic fragments. Because filter feeder organisms ingest MP while feeding, they are likely to be impacted by MP pollution. To assess the impact of polystyrene microspheres (micro-PS) on the physiology of the Pacific oyster, adult oysters were experimentally exposed to virgin micro-PS (2 and 6 um in diameter; 0.023 mg.L(-1)) for 2 mo during a reproductive cycle. Effects were investigated on ecophysiological parameters; cellular, transcriptomic, and proteomic responses; fecundity; and offspring development. Oysters preferentially ingested the 6-um micro-PS over the 2-um diameter particles. Consumption of microalgae and absorption efficiency were significantly higher in exposed oysters, suggesting compensatory and physical effects on both digestive parameters. After 2 mo, exposed oysters had significant decreases in oocyte number (-38%), diameter (-5%), and sperm velocity (-23%). The D-larval yield and larval development of offspring derived from exposed parents decreased by 41% and 18%, respectively, compared with control offspring. Dynamic energy budget modeling, supported by transcriptomic profiles, suggested a significant shift of energy allocation from reproduction to structural growth, and elevated maintenance costs in exposed oysters, which is thought to be caused by interference with energy uptake. Molecular signatures of endocrine disruption were also revealed, but no endocrine disruptors were found in the biological samples. This study provides evidence that micro-PS cause feeding modifications and reproductive disruption in oysters, with significant impacts on offspring. PMID- 26831073 TI - Huntingtin exon 1 fibrils feature an interdigitated beta-hairpin-based polyglutamine core. AB - Polyglutamine expansion within the exon1 of huntingtin leads to protein misfolding, aggregation, and cytotoxicity in Huntington's disease. This incurable neurodegenerative disease is the most prevalent member of a family of CAG repeat expansion disorders. Although mature exon1 fibrils are viable candidates for the toxic species, their molecular structure and how they form have remained poorly understood. Using advanced magic angle spinning solid-state NMR, we directly probe the structure of the rigid core that is at the heart of huntingtin exon1 fibrils and other polyglutamine aggregates, via measurements of long-range intramolecular and intermolecular contacts, backbone and side-chain torsion angles, relaxation measurements, and calculations of chemical shifts. These experiments reveal the presence of beta-hairpin-containing beta-sheets that are connected through interdigitating extended side chains. Despite dramatic differences in aggregation behavior, huntingtin exon1 fibrils and other polyglutamine-based aggregates contain identical beta-strand-based cores. Prior structural models, derived from X-ray fiber diffraction and computational analyses, are shown to be inconsistent with the solid-state NMR results. Internally, the polyglutamine amyloid fibrils are coassembled from differently structured monomers, which we describe as a type of "intrinsic" polymorphism. A stochastic polyglutamine-specific aggregation mechanism is introduced to explain this phenomenon. We show that the aggregation of mutant huntingtin exon1 proceeds via an intramolecular collapse of the expanded polyglutamine domain and discuss the implications of this observation for our understanding of its misfolding and aggregation mechanisms. PMID- 26831075 TI - Correction for Krishna Kumar et al., Limitations of GCTA as a solution to the missing heritability problem. PMID- 26831074 TI - Metabolic model for diversity-generating biosynthesis. AB - A conventional metabolic pathway leads to a specific product. In stark contrast, there are diversity-generating metabolic pathways that naturally produce different chemicals, sometimes of great diversity. We demonstrate that for one such pathway, tru, each ensuing metabolic step is slower, in parallel with the increasing potential chemical divergence generated as the pathway proceeds. Intermediates are long lived and accumulate progressively, in contrast with conventional metabolic pathways, in which the first step is rate-limiting and metabolic intermediates are short-lived. Understanding these fundamental differences enables several different practical applications, such as combinatorial biosynthesis, some of which we demonstrate here. We propose that these principles may provide a unifying framework underlying diversity-generating metabolism in many different biosynthetic pathways. PMID- 26831076 TI - Marine mixotrophy increases trophic transfer efficiency, mean organism size, and vertical carbon flux. AB - Mixotrophic plankton, which combine the uptake of inorganic resources and the ingestion of living prey, are ubiquitous in marine ecosystems, but their integrated biogeochemical impacts remain unclear. We address this issue by removing the strict distinction between phytoplankton and zooplankton from a global model of the marine plankton food web. This simplification allows the emergence of a realistic trophic network with increased fidelity to empirical estimates of plankton community structure and elemental stoichiometry, relative to a system in which autotrophy and heterotrophy are mutually exclusive. Mixotrophy enhances the transfer of biomass to larger sizes classes further up the food chain, leading to an approximately threefold increase in global mean organism size and an ~35% increase in sinking carbon flux. PMID- 26831077 TI - Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters. AB - Recent genomic studies challenge the conventional model that each metastasis must arise from a single tumor cell and instead reveal that metastases can be composed of multiple genetically distinct clones. These intriguing observations raise the question: How do polyclonal metastases emerge from the primary tumor? In this study, we used multicolor lineage tracing to demonstrate that polyclonal seeding by cell clusters is a frequent mechanism in a common mouse model of breast cancer, accounting for >90% of metastases. We directly observed multicolored tumor cell clusters across major stages of metastasis, including collective invasion, local dissemination, intravascular emboli, circulating tumor cell clusters, and micrometastases. Experimentally aggregating tumor cells into clusters induced a >15-fold increase in colony formation ex vivo and a >100-fold increase in metastasis formation in vivo. Intriguingly, locally disseminated clusters, circulating tumor cell clusters, and lung micrometastases frequently expressed the epithelial cytoskeletal protein, keratin 14 (K14). RNA-seq analysis revealed that K14(+) cells were enriched for desmosome and hemidesmosome adhesion complex genes, and were depleted for MHC class II genes. Depletion of K14 expression abrogated distant metastases and disrupted expression of multiple metastasis effectors, including Tenascin C (Tnc), Jagged1 (Jag1), and Epiregulin (Ereg). Taken together, our findings reveal K14 as a key regulator of metastasis and establish the concept that K14(+) epithelial tumor cell clusters disseminate collectively to colonize distant organs. PMID- 26831078 TI - Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers. AB - Cancer cells reprogram their metabolism to promote growth and proliferation. The genetic evidence pointing to the importance of the amino acid serine in tumorigenesis is striking. The gene encoding the enzyme 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the first committed step of serine biosynthesis, is overexpressed in tumors and cancer cell lines via focal amplification and nuclear factor erythroid-2-related factor 2 (NRF2)-mediated up regulation. PHGDH-overexpressing cells are exquisitely sensitive to genetic ablation of the pathway. Here, we report the discovery of a selective small molecule inhibitor of PHGDH, CBR-5884, identified by screening a library of 800,000 drug-like compounds. CBR-5884 inhibited de novo serine synthesis in cancer cells and was selectively toxic to cancer cell lines with high serine biosynthetic activity. Biochemical characterization of the inhibitor revealed that it was a noncompetitive inhibitor that showed a time-dependent onset of inhibition and disrupted the oligomerization state of PHGDH. The identification of a small molecule inhibitor of PHGDH not only enables thorough preclinical evaluation of PHGDH as a target in cancers, but also provides a tool with which to study serine metabolism. PMID- 26831079 TI - Targeting the Gdnf Gene in peritubular myoid cells disrupts undifferentiated spermatogonial cell development. AB - Spermatogonial stem cells (SSCs) are a subpopulation of undifferentiated spermatogonia located in a niche at the base of the seminiferous epithelium delimited by Sertoli cells and peritubular myoid (PM) cells. SSCs self-renew or differentiate into spermatogonia that proliferate to give rise to spermatocytes and maintain spermatogenesis. Glial cell line-derived neurotrophic factor (GDNF) is essential for this process. Sertoli cells produce GDNF and other growth factors and are commonly thought to be responsible for regulating SSC development, but limited attention has been paid to the role of PM cells in this process. A conditional knockout (cKO) of the androgen receptor gene in PM cells resulted in male infertility. We found that testosterone (T) induces GDNF expression in mouse PM cells in vitro and neonatal spermatogonia (including SSCs) co-cultured with T-treated PM cells were able to colonize testes of germ cell depleted mice after transplantation. This strongly suggested that T-regulated production of GDNF by PM cells is required for spermatogonial development, but PM cells might produce other factors in vitro that are responsible. In this study, we tested the hypothesis that production of GDNF by PM cells is essential for spermatogonial development by generating mice with a cKO of the Gdnf gene in PM cells. The cKO males sired up to two litters but became infertile due to collapse of spermatogenesis and loss of undifferentiated spermatogonia. These studies show for the first time, to our knowledge, that the production of GDNF by PM cells is essential for undifferentiated spermatogonial cell development in vivo. PMID- 26831081 TI - Richard M. Krause: Avuncular avatar of microbial science. PMID- 26831080 TI - Sequential activation and distinct functions for distal and proximal modules within the IgH 3' regulatory region. AB - As a master regulator of functional Ig heavy chain (IgH) expression, the IgH 3' regulatory region (3'RR) controls multiple transcription events at various stages of B-cell ontogeny, from newly formed B cells until the ultimate plasma cell stage. The IgH 3'RR plays a pivotal role in early B-cell receptor expression, germ-line transcription preceding class switch recombination, interactions between targeted switch (S) regions, variable region transcription before somatic hypermutation, and antibody heavy chain production, but the functional ranking of its different elements is still inaccurate, especially that of its evolutionarily conserved quasi-palindromic structure. By comparing relevant previous knockout (KO) mouse models (3'RR KO and hs3b-4 KO) to a novel mutant devoid of the 3'RR quasi-palindromic region (3'PAL KO), we pinpointed common features and differences that specify two distinct regulatory entities acting sequentially during B-cell ontogeny. Independently of exogenous antigens, the 3'RR distal part, including hs4, fine-tuned B-cell receptor expression in newly formed and naive B-cell subsets. At mature stages, the 3'RR portion including the quasi palindrome dictated antigen-dependent locus remodeling (global somatic hypermutation and class switch recombination to major isotypes) in activated B cells and antibody production in plasma cells. PMID- 26831082 TI - Quantitative nanoscale imaging of orientational order in biological filaments by polarized superresolution microscopy. AB - Essential cellular functions as diverse as genome maintenance and tissue morphogenesis rely on the dynamic organization of filamentous assemblies. For example, the precise structural organization of DNA filaments has profound consequences on all DNA-mediated processes including gene expression, whereas control over the precise spatial arrangement of cytoskeletal protein filaments is key for mechanical force generation driving animal tissue morphogenesis. Polarized fluorescence is currently used to extract structural organization of fluorescently labeled biological filaments by determining the orientation of fluorescent labels, however with a strong drawback: polarized fluorescence imaging is indeed spatially limited by optical diffraction, and is thus unable to discriminate between the intrinsic orientational mobility of the fluorophore labels and the real structural disorder of the labeled biomolecules. Here, we demonstrate that quantitative single-molecule polarized detection in biological filament assemblies allows not only to correct for the rotational flexibility of the label but also to image orientational order of filaments at the nanoscale using superresolution capabilities. The method is based on polarized direct stochastic optical reconstruction microscopy, using dedicated optical scheme and image analysis to determine both molecular localization and orientation with high precision. We apply this method to double-stranded DNA in vitro and microtubules and actin stress fibers in whole cells. PMID- 26831083 TI - Winning a competition predicts dishonest behavior. AB - Winning a competition engenders subsequent unrelated unethical behavior. Five studies reveal that after a competition has taken place winners behave more dishonestly than competition losers. Studies 1 and 2 demonstrate that winning a competition increases the likelihood of winners to steal money from their counterparts in a subsequent unrelated task. Studies 3a and 3b demonstrate that the effect holds only when winning means performing better than others (i.e., determined in reference to others) but not when success is determined by chance or in reference to a personal goal. Finally, study 4 demonstrates that a possible mechanism underlying the effect is an enhanced sense of entitlement among competition winners. PMID- 26831084 TI - Enhanced stability of tristetraprolin mRNA protects mice against immune-mediated inflammatory pathologies. AB - Tristetraprolin (TTP) is an inducible, tandem zinc-finger mRNA binding protein that binds to adenylate-uridylate-rich elements (AREs) in the 3'-untranslated regions (3'UTRs) of specific mRNAs, such as that encoding TNF, and increases their rates of deadenylation and turnover. Stabilization of Tnf mRNA and other cytokine transcripts in TTP-deficient mice results in the development of a profound, chronic inflammatory syndrome characterized by polyarticular arthritis, dermatitis, myeloid hyperplasia, and autoimmunity. To address the hypothesis that increasing endogenous levels of TTP in an intact animal might be beneficial in the treatment of inflammatory diseases, we generated a mouse model (TTPDeltaARE) in which a 136-base instability motif in the 3'UTR of TTP mRNA was deleted in the endogenous genetic locus. These mice appeared normal, but cultured fibroblasts and macrophages derived from them exhibited increased stability of the otherwise highly labile TTP mRNA. This resulted in increased TTP protein expression in LPS stimulated macrophages and increased levels of TTP protein in mouse tissues. TTPDeltaARE mice were protected from collagen antibody-induced arthritis, exhibited significantly reduced inflammation in imiquimod-induced dermatitis, and were resistant to induction of experimental autoimmune encephalomyelitis, presumably by dampening the excessive production of proinflammatory mediators in all cases. These data suggest that increased systemic levels of TTP, secondary to increased stability of its mRNA throughout the body, can be protective against inflammatory disease in certain models and might be viewed as an attractive therapeutic target for the treatment of human inflammatory diseases. PMID- 26831085 TI - Structure-based analysis of the molecular interactions between acyltransferase and acyl carrier protein in vicenistatin biosynthesis. AB - Acyltransferases (ATs) are key determinants of building block specificity in polyketide biosynthesis. Despite the importance of protein-protein interactions between AT and acyl carrier protein (ACP) during the acyltransfer reaction, the mechanism of ACP recognition by AT is not understood in detail. Herein, we report the crystal structure of AT VinK, which transfers a dipeptide group between two ACPs, VinL and VinP1LdACP, in vicenistatin biosynthesis. The isolated VinK structure showed a unique substrate-binding pocket for the dipeptide group linked to ACP. To gain greater insight into the mechanism of ACP recognition, we attempted to crystallize the VinK-ACP complexes. Because transient enzyme-ACP complexes are difficult to crystallize, we developed a covalent cross-linking strategy using a bifunctional maleimide reagent to trap the VinK-ACP complexes, allowing the determination of the crystal structure of the VinK-VinL complex. In the complex structure, Arg-153, Met-206, and Arg-299 of VinK interact with the negatively charged helix II region of VinL. The VinK-VinL complex structure allows, to our knowledge, the first visualization of the interaction between AT and ACP and provides detailed mechanistic insights into ACP recognition by AT. PMID- 26831086 TI - Defining the rate-limiting processes of bacterial cytokinesis. AB - Bacterial cytokinesis is accomplished by the essential 'divisome' machinery. The most widely conserved divisome component, FtsZ, is a tubulin homolog that polymerizes into the 'FtsZ-ring' ('Z-ring'). Previous in vitro studies suggest that Z-ring contraction serves as a major constrictive force generator to limit the progression of cytokinesis. Here, we applied quantitative superresolution imaging to examine whether and how Z-ring contraction limits the rate of septum closure during cytokinesis in Escherichia coli cells. Surprisingly, septum closure rate was robust to substantial changes in all Z-ring properties proposed to be coupled to force generation: FtsZ's GTPase activity, Z-ring density, and the timing of Z-ring assembly and disassembly. Instead, the rate was limited by the activity of an essential cell wall synthesis enzyme and further modulated by a physical divisome-chromosome coupling. These results challenge a Z-ring-centric view of bacterial cytokinesis and identify cell wall synthesis and chromosome segregation as limiting processes of cytokinesis. PMID- 26831087 TI - Tle1 tumor suppressor negatively regulates inflammation in vivo and modulates NF kappaB inflammatory pathway. AB - Tle1 (transducin-like enhancer of split 1) is a corepressor that interacts with a variety of DNA-binding transcription factors and has been implicated in many cellular functions; however, physiological studies are limited. Tle1-deficient (Tle1(Delta/Delta)) mice, although grossly normal at birth, exhibit skin defects, lung hypoplasia, severe runting, poor body condition, and early mortality. Tle1(Delta/Delta) mice display a chronic inflammatory phenotype with increased expression of inflammatory cytokines and chemokines in the skin, lung, and intestine and increased circulatory IL-6 and G-CSF, along with a hematopoietic shift toward granulocyte macrophage progenitor and myeloid cells. Tle1(Delta/Delta) macrophages produce increased inflammatory cytokines in response to Toll-like receptor (TLR) agonists and lipopolysaccharides (LPS), and Tle1(Delta/Delta) mice display an enhanced inflammatory response to ear skin 12-O tetradecanoylphorbol-13-acetate treatment. Loss of Tle1 not only results in increased phosphorylation and activation of proinflammatory NF-kappaB but also results in decreased Hes1 (hairy and enhancer of split-1), a negative regulator of inflammation in macrophages. Furthermore, Tle1(Delta/Delta) mice exhibit accelerated growth of B6-F10 melanoma xenografts. Our work provides the first in vivo evidence, to our knowledge, that TLE1 is a major counterregulator of inflammation with potential roles in a variety of inflammatory diseases and in cancer progression. PMID- 26831089 TI - Two types of quasi-liquid layers on ice crystals are formed kinetically. AB - Surfaces of ice are covered with thin liquid water layers, called quasi-liquid layers (QLLs), even below their melting point (0 degrees C), which govern a wide variety of phenomena in nature. We recently found that two types of QLL phases appear that exhibit different morphologies (droplets and thin layers) [Sazaki G. et al. (2012) Proc Natl Acad Sci USA 109(4):1052-1055]. However, revealing the thermodynamic stabilities of QLLs remains a longstanding elusive problem. Here we show that both types of QLLs are metastable phases that appear only if the water vapor pressure is higher than a certain critical supersaturation. We directly visualized the QLLs on ice crystal surfaces by advanced optical microscopy, which can detect 0.37-nm-thick elementary steps on ice crystal surfaces. At a certain fixed temperature, as the water vapor pressure decreased, thin-layer QLLs first disappeared, and then droplet QLLs vanished next, although elementary steps of ice crystals were still growing. These results clearly demonstrate that both types of QLLs are kinetically formed, not by the melting of ice surfaces, but by the deposition of supersaturated water vapor on ice surfaces. To our knowledge, this is the first experimental evidence that supersaturation of water vapor plays a crucially important role in the formation of QLLs. PMID- 26831088 TI - Promoting axon regeneration in the adult CNS by modulation of the melanopsin/GPCR signaling. AB - Cell-type-specific G protein-coupled receptor (GPCR) signaling regulates distinct neuronal responses to various stimuli and is essential for axon guidance and targeting during development. However, its function in axonal regeneration in the mature CNS remains elusive. We found that subtypes of intrinsically photosensitive retinal ganglion cells (ipRGCs) in mice maintained high mammalian target of rapamycin (mTOR) levels after axotomy and that the light-sensitive GPCR melanopsin mediated this sustained expression. Melanopsin overexpression in the RGCs stimulated axonal regeneration after optic nerve crush by up-regulating mTOR complex 1 (mTORC1). The extent of the regeneration was comparable to that observed after phosphatase and tensin homolog (Pten) knockdown. Both the axon regeneration and mTOR activity that were enhanced by melanopsin required light stimulation and Gq/11 signaling. Specifically, activating Gq in RGCs elevated mTOR activation and promoted axonal regeneration. Melanopsin overexpression in RGCs enhanced the amplitude and duration of their light response, and silencing them with Kir2.1 significantly suppressed the increased mTOR signaling and axon regeneration that were induced by melanopsin. Thus, our results provide a strategy to promote axon regeneration after CNS injury by modulating neuronal activity through GPCR signaling. PMID- 26831090 TI - Complexation and coacervation of like-charged polyelectrolytes inspired by mussels. AB - It is well known that polyelectrolyte complexes and coacervates can form on mixing oppositely charged polyelectrolytes in aqueous solutions, due to mainly electrostatic attraction between the oppositely charged polymers. Here, we report the first (to the best of our knowledge) complexation and coacervation of two positively charged polyelectrolytes, which provides a new paradigm for engineering strong, self-healing interactions between polyelectrolytes underwater and a new marine mussel-inspired underwater adhesion mechanism. Unlike the conventional complex coacervate, the like-charged coacervate is aggregated by strong short-range cation-pi interactions by overcoming repulsive electrostatic interactions. The resultant phase of the like-charged coacervate comprises a thin and fragile polyelectrolyte framework and round and regular pores, implying a strong electrostatic correlation among the polyelectrolyte frameworks. The like charged coacervate possesses a very low interfacial tension, which enables this highly positively charged coacervate to be applied to capture, carry, or encapsulate anionic biomolecules and particles with a broad range of applications. PMID- 26831092 TI - New approaches to quantifying aerosol influence on the cloud radiative effect. AB - The topic of cloud radiative forcing associated with the atmospheric aerosol has been the focus of intense scrutiny for decades. The enormity of the problem is reflected in the need to understand aspects such as aerosol composition, optical properties, cloud condensation, and ice nucleation potential, along with the global distribution of these properties, controlled by emissions, transport, transformation, and sinks. Equally daunting is that clouds themselves are complex, turbulent, microphysical entities and, by their very nature, ephemeral and hard to predict. Atmospheric general circulation models represent aerosol cloud interactions at ever-increasing levels of detail, but these models lack the resolution to represent clouds and aerosol-cloud interactions adequately. There is a dearth of observational constraints on aerosol-cloud interactions. We develop a conceptual approach to systematically constrain the aerosol-cloud radiative effect in shallow clouds through a combination of routine process modeling and satellite and surface-based shortwave radiation measurements. We heed the call to merge Darwinian and Newtonian strategies by balancing microphysical detail with scaling and emergent properties of the aerosol-cloud radiation system. PMID- 26831093 TI - Global informatics and physical property selection in protein sequences. AB - The degree of informatic independence between the physical properties of amino acids as encoded in actual protein sequences is calculated. It is shown that no physical property can be identified that carries significantly less information than others and that the information overlap between different properties and different length scales along the sequence is essentially zero. These observations suggest that bioinformatic models based on arbitrarily selected sets of physical properties are inherently deficient. PMID- 26831091 TI - Regional specialization within the human striatum for diverse psychological functions. AB - Decades of animal and human neuroimaging research have identified distinct, but overlapping, striatal zones, which are interconnected with separable corticostriatal circuits, and are crucial for the organization of functional systems. Despite continuous efforts to subdivide the human striatum based on anatomical and resting-state functional connectivity, characterizing the different psychological processes related to each zone remains a work in progress. Using an unbiased, data-driven approach, we analyzed large-scale coactivation data from 5,809 human imaging studies. We (i) identified five distinct striatal zones that exhibited discrete patterns of coactivation with cortical brain regions across distinct psychological processes and (ii) identified the different psychological processes associated with each zone. We found that the reported pattern of cortical activation reliably predicted which striatal zone was most strongly activated. Critically, activation in each functional zone could be associated with distinct psychological processes directly, rather than inferred indirectly from psychological functions attributed to associated cortices. Consistent with well-established findings, we found an association of the ventral striatum (VS) with reward processing. Confirming less well-established findings, the VS and adjacent anterior caudate were associated with evaluating the value of rewards and actions, respectively. Furthermore, our results confirmed a sometimes overlooked specialization of the posterior caudate nucleus for executive functions, often considered the exclusive domain of frontoparietal cortical circuits. Our findings provide a precise functional map of regional specialization within the human striatum, both in terms of the differential cortical regions and psychological functions associated with each striatal zone. PMID- 26831094 TI - Distinct signaling of Drosophila chemoreceptors in olfactory sensory neurons. AB - In Drosophila, olfactory sensory neurons (OSNs) rely primarily on two types of chemoreceptors, odorant receptors (Ors) and ionotropic receptors (Irs), to convert odor stimuli into neural activity. The cellular signaling of these receptors in their native OSNs remains unclear because of the difficulty of obtaining intracellular recordings from Drosophila OSNs. Here, we developed an antennal preparation that enabled the first recordings (to our knowledge) from targeted Drosophila OSNs through a patch-clamp technique. We found that brief odor pulses triggered graded inward receptor currents with distinct response kinetics and current-voltage relationships between Or- and Ir-driven responses. When stimulated with long-step odors, the receptor current of Ir-expressing OSNs did not adapt. In contrast, Or-expressing OSNs showed a strong Ca(2+)-dependent adaptation. The adaptation-induced changes in odor sensitivity obeyed the Weber Fechner relation; however, surprisingly, the incremental sensitivity was reduced at low odor backgrounds but increased at high odor backgrounds. Our model for odor adaptation revealed two opposing effects of adaptation, desensitization and prevention of saturation, in dynamically adjusting odor sensitivity and extending the sensory operating range. PMID- 26831095 TI - Integrated in vivo and in vitro nascent chain profiling reveals widespread translational pausing. AB - Although the importance of the nonuniform progression of elongation in translation is well recognized, there have been few attempts to explore this process by directly profiling nascent polypeptides, the relevant intermediates of translation. Such approaches will be essential to complement other approaches, including ribosome profiling, which is extremely powerful but indirect with respect to the actual translation processes. Here, we use the nascent polypeptide's chemical trait of having a covalently attached tRNA moiety to detect translation intermediates. In a case study, Escherichia coli SecA was shown to undergo nascent polypeptide-dependent translational pauses. We then carried out integrated in vivo and in vitro nascent chain profiling (iNP) to characterize 1,038 proteome members of E. coli that were encoded by the first quarter of the chromosome with respect to their propensities to accumulate polypeptidyl-tRNA intermediates. A majority of them indeed undergo single or multiple pauses, some occurring only in vitro, some occurring only in vivo, and some occurring both in vivo and in vitro. Thus, translational pausing can be intrinsically robust, subject to in vivo alleviation, or require in vivo reinforcement. Cytosolic and membrane proteins tend to experience different classes of pauses; membrane proteins often pause multiple times in vivo. We also note that the solubility of cytosolic proteins correlates with certain categories of pausing. Translational pausing is widespread and diverse in nature. PMID- 26831096 TI - Multiplexed autoantigen microarrays identify HLA as a key driver of anti desmoglein and -non-desmoglein reactivities in pemphigus. AB - Patients with pemphigus vulgaris (PV) harbor antibodies reactive against self antigens expressed at the surface of keratinocytes, primarily desmoglein (Dsg) 3 and, to a lesser extent, Dsg1. Conventionally, only antibodies targeting these molecules have been thought to contribute to disease pathogenesis. This notion has been challenged by a growing pool of evidence that suggests that antibodies toward additional targets may play a role in disease. The aims of this study were to (i) establish high-throughput protein microarray technology as a method to investigate traditional and putative autoantibodies (autoAbs) in PV and (ii) use multiplexed protein array technology to define the scope and specificity of the autoAb response in PV. Our analysis demonstrated significant IgG reactivity in patients with PV toward the muscarinic acetylcholine receptor subtypes 3, 4, and 5 as well as thyroid peroxidase. Furthermore, we found that healthy first- and second-degree relatives of patients with PV express autoAbs toward desmoglein and non-Dsg targets. Our analysis also identified genetic elements, particularly HLA, as key drivers of autoAb expression. Finally, we show that patients with PV exhibit significantly reduced IgM reactivity toward disease-associated antigens relative to controls. The use of protein microarrays to profile the autoAb response in PV advanced the current understanding of disease and provided insight into the complex relationship between genetics and disease development. PMID- 26831098 TI - Evolution and convergence of the patterns of international scientific collaboration. AB - International research collaboration plays an important role in the social construction and evolution of science. Studies of science increasingly analyze international collaboration across multiple organizations for its impetus in improving research quality, advancing efficiency of the scientific production, and fostering breakthroughs in a shorter time. However, long-run patterns of international research collaboration across scientific fields and their structural changes over time are hardly known. Here we show the convergence of international scientific collaboration across research fields over time. Our study uses a dataset by the National Science Foundation and computes the fraction of papers that have international institutional coauthorships for various fields of science. We compare our results with pioneering studies carried out in the 1970s and 1990s by applying a standardization method that transforms all fractions of internationally coauthored papers into a comparable framework. We find, over 1973-2012, that the evolution of collaboration patterns across scientific disciplines seems to generate a convergence between applied and basic sciences. We also show that the general architecture of international scientific collaboration, based on the ranking of fractions of international coauthorships for different scientific fields per year, has tended to be unchanged over time, at least until now. Overall, this study shows, to our knowledge for the first time, the evolution of the patterns of international scientific collaboration starting from initial results described by literature in the 1970s and 1990s. We find a convergence of these long-run collaboration patterns between the applied and basic sciences. This convergence might be one of contributing factors that supports the evolution of modern scientific fields. PMID- 26831097 TI - ABA receptor PYL9 promotes drought resistance and leaf senescence. AB - Drought stress is an important environmental factor limiting plant productivity. In this study, we screened drought-resistant transgenic plants from 65 promoter pyrabactin resistance 1-like (PYL) abscisic acid (ABA) receptor gene combinations and discovered that pRD29A::PYL9 transgenic lines showed dramatically increased drought resistance and drought-induced leaf senescence in both Arabidopsis and rice. Previous studies suggested that ABA promotes senescence by causing ethylene production. However, we found that ABA promotes leaf senescence in an ethylene independent manner by activating sucrose nonfermenting 1-related protein kinase 2s (SnRK2s), which subsequently phosphorylate ABA-responsive element-binding factors (ABFs) and Related to ABA-Insensitive 3/VP1 (RAV1) transcription factors. The phosphorylated ABFs and RAV1 up-regulate the expression of senescence associated genes, partly by up-regulating the expression of Oresara 1. The pyl9 and ABA-insensitive 1-1 single mutants, pyl8-1pyl9 double mutant, and snrk2.2/3/6 triple mutant showed reduced ABA-induced leaf senescence relative to the WT, whereas pRD29A::PYL9 transgenic plants showed enhanced ABA-induced leaf senescence. We found that leaf senescence may benefit drought resistance by helping to generate an osmotic potential gradient, which is increased in pRD29A::PYL9 transgenic plants and causes water to preferentially flow to developing tissues. Our results uncover the molecular mechanism of ABA-induced leaf senescence and suggest an important role of PYL9 and leaf senescence in promoting resistance to extreme drought stress. PMID- 26831099 TI - Disentangling the mechanisms behind climate effects on zooplankton. AB - Understanding how climate influences ecosystems is complicated by the many correlated and interrelated impacting factors. Here we quantify climate effects on Calanus finmarchicus in the northeastern Norwegian Sea and southwestern Barents Sea. By combining oceanographic drift models and statistical analyses of field data from 1959 to 1993 and investigating effects across trophic levels, we are able to elucidate pathways by which climate influences zooplankton. The results show that both chlorophyll biomass in spring and C. finmarchicus biomass in summer relate positively to a combination of shallow mixed layer depth and increased wind in spring, suggesting that C. finmarchicus biomass in summer is influenced by bottom-up effects of food availability. Furthermore, spatially resolved C. finmarchicus biomass in summer is linked to favorable transport from warmer, core areas to the south. However, increased mean temperature in spring does not lead to increased C. finmarchicus biomass in summer. Rather, spring biomass is generally higher, but population growth from spring to summer is lower, after a warm compared with a cold spring. Our study illustrates how improved understanding of climate effects can be obtained when different datasets and different methods are combined in a unified approach. PMID- 26831101 TI - Policy impacts of ecosystem services knowledge. AB - Research about ecosystem services (ES) often aims to generate knowledge that influences policies and institutions for conservation and human development. However, we have limited understanding of how decision-makers use ES knowledge or what factors facilitate use. Here we address this gap and report on, to our knowledge, the first quantitative analysis of the factors and conditions that explain the policy impact of ES knowledge. We analyze a global sample of cases where similar ES knowledge was generated and applied to decision-making. We first test whether attributes of ES knowledge themselves predict different measures of impact on decisions. We find that legitimacy of knowledge is more often associated with impact than either the credibility or salience of the knowledge. We also examine whether predictor variables related to the science-to-policy process and the contextual conditions of a case are significant in predicting impact. Our findings indicate that, although many factors are important, attributes of the knowledge and aspects of the science-to-policy process that enhance legitimacy best explain the impact of ES science on decision-making. Our results are consistent with both theory and previous qualitative assessments in suggesting that the attributes and perceptions of scientific knowledge and process within which knowledge is coproduced are important determinants of whether that knowledge leads to action. PMID- 26831100 TI - Toll-like receptor-5 agonist, entolimod, suppresses metastasis and induces immunity by stimulating an NK-dendritic-CD8+ T-cell axis. AB - Activation of an anticancer innate immune response is highly desirable because of its inherent ability to generate an adaptive antitumor T-cell response. However, insufficient safety of innate immune modulators limits clinical use to topical applications. Toll-like receptor 5 (TLR5) agonists are favorably positioned as potential systemic immunotherapeutic agents because of unusual tissue specificity of expression, uniquely safe profile of induced cytokines, and antitumor efficacy demonstrated in a number of animal models. Here, we decipher the molecular and cellular events underlying the metastasis suppressive activity of entolimod, a clinical stage TLR5 agonist that activates NF-kappaB-, AP-1-, and STAT3-driven immunomodulatory signaling pathways specifically within the liver. Used as a single agent in murine colon and mammary metastatic cancer models, entolimod rapidly induces CXCL9 and -10 that support homing of blood-borne CXCR3-expressing NK cells to the liver predominantly through an IFN-gamma signaling independent mechanism. NK cell-dependent activation of dendritic cells is followed by stimulation of a CD8(+) T-cell response, which exert both antimetastatic effect of entolimod and establishment of tumor-specific and durable immune memory. These results define systemically administered TLR5 agonists as organ-specific immunoadjuvants, enabling efficient antitumor vaccination that does not depend on identification of tumor-specific antigens. PMID- 26831102 TI - Selective memory retrieval of auditory what and auditory where involves the ventrolateral prefrontal cortex. AB - There is evidence from the visual, verbal, and tactile memory domains that the midventrolateral prefrontal cortex plays a critical role in the top-down modulation of activity within posterior cortical areas for the selective retrieval of specific aspects of a memorized experience, a functional process often referred to as active controlled retrieval. In the present functional neuroimaging study, we explore the neural bases of active retrieval for auditory nonverbal information, about which almost nothing is known. Human participants were scanned with functional magnetic resonance imaging (fMRI) in a task in which they were presented with short melodies from different locations in a simulated virtual acoustic environment within the scanner and were then instructed to retrieve selectively either the particular melody presented or its location. There were significant activity increases specifically within the midventrolateral prefrontal region during the selective retrieval of nonverbal auditory information. During the selective retrieval of information from auditory memory, the right midventrolateral prefrontal region increased its interaction with the auditory temporal region and the inferior parietal lobule in the right hemisphere. These findings provide evidence that the midventrolateral prefrontal cortical region interacts with specific posterior cortical areas in the human cerebral cortex for the selective retrieval of object and location features of an auditory memory experience. PMID- 26831103 TI - In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward. AB - The reinforcing and rewarding properties of cocaine are attributed to its ability to increase dopaminergic transmission in nucleus accumbens (NAc). This action reinforces drug taking and seeking and leads to potent and long-lasting associations between the rewarding effects of the drug and the cues associated with its availability. The inability to extinguish these associations is a key factor contributing to relapse. Dopamine produces these effects by controlling the activity of two subpopulations of NAc medium spiny neurons (MSNs) that are defined by their predominant expression of either dopamine D1 or D2 receptors. Previous work has demonstrated that optogenetically stimulating D1 MSNs promotes reward, whereas stimulating D2 MSNs produces aversion. However, we still lack a clear understanding of how the endogenous activity of these cell types is affected by cocaine and encodes information that drives drug-associated behaviors. Using fiber photometry calcium imaging we define D1 MSNs as the specific population of cells in NAc that encodes information about drug associations and elucidate the temporal profile with which D1 activity is increased to drive drug seeking in response to contextual cues. Chronic cocaine exposure dysregulates these D1 signals to both prevent extinction and facilitate reinstatement of drug seeking to drive relapse. Directly manipulating these D1 signals using designer receptors exclusively activated by designer drugs prevents contextual associations. Together, these data elucidate the responses of D1- and D2-type MSNs in NAc to acute cocaine and during the formation of context-reward associations and define how prior cocaine exposure selectively dysregulates D1 signaling to drive relapse. PMID- 26831104 TI - TLR4/MD-2 activation by a synthetic agonist with no similarity to LPS. AB - Structurally disparate molecules reportedly engage and activate Toll-like receptor (TLR) 4 and other TLRs, yet the interactions that mediate binding and activation by dissimilar ligands remain unknown. We describe Neoseptins, chemically synthesized peptidomimetics that bear no structural similarity to the established TLR4 ligand, lipopolysaccharide (LPS), but productively engage the mouse TLR4 (mTLR4)/myeloid differentiation factor 2 (MD-2) complex. Neoseptin-3 activates mTLR4/MD-2 independently of CD14 and triggers canonical myeloid differentiation primary response gene 88 (MyD88)- and Toll-interleukin 1 receptor (TIR) domain-containing adaptor inducing IFN-beta (TRIF)-dependent signaling. The crystal structure mTLR4/MD-2/Neoseptin-3 at 2.57-A resolution reveals that Neoseptin-3 binds as an asymmetrical dimer within the hydrophobic pocket of MD-2, inducing an active receptor complex similar to that induced by lipid A. However, Neoseptin-3 and lipid A form dissimilar molecular contacts to achieve receptor activation; hence strong TLR4/MD-2 agonists need not mimic LPS. PMID- 26831105 TI - General 2.5 power law of metallic glasses. AB - Metallic glass (MG) is an important new category of materials, but very few rigorous laws are currently known for defining its "disordered" structure. Recently we found that under compression, the volume (V) of an MG changes precisely to the 2.5 power of its principal diffraction peak position (1/q1). In the present study, we find that this 2.5 power law holds even through the first order polyamorphic transition of a Ce68Al10Cu20Co2 MG. This transition is, in effect, the equivalent of a continuous "composition" change of 4f-localized "big Ce" to 4f-itinerant "small Ce," indicating the 2.5 power law is general for tuning with composition. The exactness and universality imply that the 2.5 power law may be a general rule defining the structure of MGs. PMID- 26831106 TI - Chimera proteins with affinity for membranes and microtubule tips polarize in the membrane of fission yeast cells. AB - Cell polarity refers to a functional spatial organization of proteins that is crucial for the control of essential cellular processes such as growth and division. To establish polarity, cells rely on elaborate regulation networks that control the distribution of proteins at the cell membrane. In fission yeast cells, a microtubule-dependent network has been identified that polarizes the distribution of signaling proteins that restricts growth to cell ends and targets the cytokinetic machinery to the middle of the cell. Although many molecular components have been shown to play a role in this network, it remains unknown which molecular functionalities are minimally required to establish a polarized protein distribution in this system. Here we show that a membrane-binding protein fragment, which distributes homogeneously in wild-type fission yeast cells, can be made to concentrate at cell ends by attaching it to a cytoplasmic microtubule end-binding protein. This concentration results in a polarized pattern of chimera proteins with a spatial extension that is very reminiscent of natural polarity patterns in fission yeast. However, chimera levels fluctuate in response to microtubule dynamics, and disruption of microtubules leads to disappearance of the pattern. Numerical simulations confirm that the combined functionality of membrane anchoring and microtubule tip affinity is in principle sufficient to create polarized patterns. Our chimera protein may thus represent a simple molecular functionality that is able to polarize the membrane, onto which additional layers of molecular complexity may be built to provide the temporal robustness that is typical of natural polarity patterns. PMID- 26831107 TI - Geomorphic controls on elevational gradients of species richness. AB - Elevational gradients of biodiversity have been widely investigated, and yet a clear interpretation of the biotic and abiotic factors that determine how species richness varies with elevation is still elusive. In mountainous landscapes, habitats at different elevations are characterized by different areal extent and connectivity properties, key drivers of biodiversity, as predicted by metacommunity theory. However, most previous studies directly correlated species richness to elevational gradients of potential drivers, thus neglecting the interplay between such gradients and the environmental matrix. Here, we investigate the role of geomorphology in shaping patterns of species richness. We develop a spatially explicit zero-sum metacommunity model where species have an elevation-dependent fitness and otherwise neutral traits. Results show that ecological dynamics over complex terrains lead to the null expectation of a hump shaped elevational gradient of species richness, a pattern widely observed empirically. Local species richness is found to be related to the landscape elevational connectivity, as quantified by a newly proposed metric that applies tools of complex network theory to measure the closeness of a site to others with similar habitat. Our theoretical results suggest clear geomorphic controls on elevational gradients of species richness and support the use of the landscape elevational connectivity as a null model for the analysis of the distribution of biodiversity. PMID- 26831108 TI - Asymmetric ecological conditions favor Red-Queen type of continued evolution over stasis. AB - Four decades ago, Leigh Van Valen presented the Red Queen's hypothesis to account for evolution of species within a multispecies ecological community [Van Valen L (1973) Evol Theory 1(1):1-30]. The overall conclusion of Van Valen's analysis was that evolution would continue even in the absence of abiotic perturbations. Stenseth and Maynard Smith presented in 1984 [Stenseth NC, Maynard Smith J (1984) Evolution 38(4):870-880] a model for the Red Queen's hypothesis showing that both Red-Queen type of continuous evolution and stasis could result from a model with biotically driven evolution. However, although that contribution demonstrated that both evolutionary outcomes were possible, it did not identify which ecological conditions would lead to each of these evolutionary outcomes. Here, we provide, using a simple, yet general population-biologically founded eco evolutionary model, such analytically derived conditions: Stasis will predominantly emerge whenever the ecological system contains only symmetric ecological interactions, whereas both Red-Queen and stasis type of evolution may result if the ecological interactions are asymmetrical, and more likely so with increasing degree of asymmetry in the ecological system (i.e., the more trophic interactions, host-pathogen interactions, and the like there are [i.e., +/- type of ecological interactions as well as asymmetric competitive (-/-) and mutualistic (+/+) ecological interactions]). In the special case of no between generational genetic variance, our results also predict dynamics within these types of purely ecological systems. PMID- 26831109 TI - C0 and C1 N-terminal Ig domains of myosin binding protein C exert different effects on thin filament activation. AB - Mutations in genes encoding myosin, the molecular motor that powers cardiac muscle contraction, and its accessory protein, cardiac myosin binding protein C (cMyBP-C), are the two most common causes of hypertrophic cardiomyopathy (HCM). Recent studies established that the N-terminal domains (NTDs) of cMyBP-C (e.g., C0, C1, M, and C2) can bind to and activate or inhibit the thin filament (TF). However, the molecular mechanism(s) by which NTDs modulate interaction of myosin with the TF remains unknown and the contribution of each individual NTD to TF activation/inhibition is unclear. Here we used an integrated structure-function approach using cryoelectron microscopy, biochemical kinetics, and force measurements to reveal how the first two Ig-like domains of cMyPB-C (C0 and C1) interact with the TF. Results demonstrate that despite being structural homologs, C0 and C1 exhibit different patterns of binding on the surface of F-actin. Importantly, C1 but not C0 binds in a position to activate the TF by shifting tropomyosin (Tm) to the "open" structural state. We further show that C1 directly interacts with Tm and traps Tm in the open position on the surface of F-actin. Both C0 and C1 compete with myosin subfragment 1 for binding to F-actin and effectively inhibit actomyosin interactions when present at high ratios of NTDs to F-actin. Finally, we show that in contracting sarcomeres, the activating effect of C1 is apparent only once low levels of Ca(2+) have been achieved. We suggest that Ca(2+) modulates the interaction of cMyBP-C with the TF in the sarcomere. PMID- 26831110 TI - Myotubes derived from human-induced pluripotent stem cells mirror in vivo insulin resistance. AB - Induced pluripotent stem cells (iPS cells) represent a unique tool for the study of the pathophysiology of human disease, because these cells can be differentiated into multiple cell types in vitro and used to generate patient- and tissue-specific disease models. Given the critical role for skeletal muscle insulin resistance in whole-body glucose metabolism and type 2 diabetes, we have created a novel cellular model of human muscle insulin resistance by differentiating iPS cells from individuals with mutations in the insulin receptor (IR-Mut) into functional myotubes and characterizing their response to insulin in comparison with controls. Morphologically, IR-Mut cells differentiated normally, but had delayed expression of some muscle differentiation-related genes. Most importantly, whereas control iPS-derived myotubes exhibited in vitro responses similar to primary differentiated human myoblasts, IR-Mut myotubes demonstrated severe impairment in insulin signaling and insulin-stimulated 2-deoxyglucose uptake and glycogen synthesis. Transcriptional regulation was also perturbed in IR-Mut myotubes with reduced insulin-stimulated expression of metabolic and early growth response genes. Thus, iPS-derived myotubes from individuals with genetically determined insulin resistance demonstrate many of the defects observed in vivo in insulin-resistant skeletal muscle and provide a new model to analyze the molecular impact of muscle insulin resistance. PMID- 26831111 TI - An ecocultural model predicts Neanderthal extinction through competition with modern humans. AB - Archaeologists argue that the replacement of Neanderthals by modern humans was driven by interspecific competition due to a difference in culture level. To assess the cogency of this argument, we construct and analyze an interspecific cultural competition model based on the Lotka-Volterra model, which is widely used in ecology, but which incorporates the culture level of a species as a variable interacting with population size. We investigate the conditions under which a difference in culture level between cognitively equivalent species, or alternatively a difference in underlying learning ability, may produce competitive exclusion of a comparatively (although not absolutely) large local Neanderthal population by an initially smaller modern human population. We find, in particular, that this competitive exclusion is more likely to occur when population growth occurs on a shorter timescale than cultural change, or when the competition coefficients of the Lotka-Volterra model depend on the difference in the culture levels of the interacting species. PMID- 26831113 TI - On the universal structure of human lexical semantics. AB - How universal is human conceptual structure? The way concepts are organized in the human brain may reflect distinct features of cultural, historical, and environmental background in addition to properties universal to human cognition. Semantics, or meaning expressed through language, provides indirect access to the underlying conceptual structure, but meaning is notoriously difficult to measure, let alone parameterize. Here, we provide an empirical measure of semantic proximity between concepts using cross-linguistic dictionaries to translate words to and from languages carefully selected to be representative of worldwide diversity. These translations reveal cases where a particular language uses a single "polysemous" word to express multiple concepts that another language represents using distinct words. We use the frequency of such polysemies linking two concepts as a measure of their semantic proximity and represent the pattern of these linkages by a weighted network. This network is highly structured: Certain concepts are far more prone to polysemy than others, and naturally interpretable clusters of closely related concepts emerge. Statistical analysis of the polysemies observed in a subset of the basic vocabulary shows that these structural properties are consistent across different language groups, and largely independent of geography, environment, and the presence or absence of a literary tradition. The methods developed here can be applied to any semantic domain to reveal the extent to which its conceptual structure is, similarly, a universal attribute of human cognition and language use. PMID- 26831112 TI - Functional evidence for TCR-intrinsic specificity for MHCII. AB - How T cells become restricted to binding antigenic peptides within class I or class II major histocompatibility complex molecules (pMHCI or pMHCII, respectively) via clonotypic T-cell receptors (TCRs) remains debated. During development, if TCR-pMHC interactions exceed an affinity threshold, a signal is generated that positively selects the thymocyte to become a mature CD4(+) or CD8(+) T cell that can recognize foreign peptides within MHCII or MHCI, respectively. But whether TCRs possess an intrinsic, subthreshold specificity for MHC that facilitates sampling of the peptides within MHC during positive selection or T-cell activation is undefined. Here we asked if increasing the frequency of lymphocyte-specific protein tyrosine kinase (Lck)-associated CD4 molecules in T-cell hybridomas would allow for the detection of subthreshold TCR MHC interactions. The reactivity of 10 distinct TCRs was assessed in response to selecting and nonselecting MHCII bearing cognate, null, or "shaved" peptides with alanine substitutions at known TCR contact residues: Three of the TCRs were selected on MHCII and have defined peptide specificity, two were selected on MHCI and have a known pMHC specificity, and five were generated in vitro without defined selecting or cognate pMHC. Our central finding is that IL-2 was made when each TCR interacted with selecting or nonselecting MHCII presenting shaved peptides. These responses were abrogated by anti-CD4 antibodies and mutagenesis of CD4. They were also inhibited by anti-MHC antibodies that block TCR-MHCII interactions. We interpret these data as functional evidence for TCR-intrinsic specificity for MHCII. PMID- 26831114 TI - miR-H28 and miR-H29 expressed late in productive infection are exported and restrict HSV-1 replication and spread in recipient cells. AB - We report on the properties and function of two herpes simplex virus-1 (HSV-1) microRNAs (miRNAs) designated "miR-H28" and "miR-H29." Both miRNAs accumulate late in productive infection at a time when, for the most part, viral DNA and proteins have been made. Ectopic expression of miRNA mimics in human cells before infection reduced the accumulation of viral mRNAs and proteins, reduced plaque sizes, and at vey low multiplicities of infection reduced viral yields. The specificity of the miRNA mimics was tested in two ways. First, ectopic expression of mimics carrying mutations in the seed sequence was ineffective. Second, in similar tests two viral miRNAs made early in productive infection also had no effect. Both miR-H28 and miR-H29 are exported from infected cells in exosomes. A noteworthy finding is that both miR-H28 and miR-H29 were absent from murine ganglia harboring latent virus but accumulated in ganglia in which the virus was induced to reactivate. The significance of these findings rests on the principle that the transmission of HSV from person to person is by physical contact between the infected tissues of the donor and those of uninfected recipient. Diminished size of primary or recurrent lesions could be predicted to enhance person-to person transmission. Reduction in the amount of reactivating latent virus would reduce the risk of retrograde transport to the CNS but would not interfere with anterograde transport to a site at or near the site of initial infection. PMID- 26831115 TI - Legionella pneumophila S1P-lyase targets host sphingolipid metabolism and restrains autophagy. AB - Autophagy is an essential component of innate immunity, enabling the detection and elimination of intracellular pathogens. Legionella pneumophila, an intracellular pathogen that can cause a severe pneumonia in humans, is able to modulate autophagy through the action of effector proteins that are translocated into the host cell by the pathogen's Dot/Icm type IV secretion system. Many of these effectors share structural and sequence similarity with eukaryotic proteins. Indeed, phylogenetic analyses have indicated their acquisition by horizontal gene transfer from a eukaryotic host. Here we report that L. pneumophila translocates the effector protein sphingosine-1 phosphate lyase (LpSpl) to target the host sphingosine biosynthesis and to curtail autophagy. Our structural characterization of LpSpl and its comparison with human SPL reveals high structural conservation, thus supporting prior phylogenetic analysis. We show that LpSpl possesses S1P lyase activity that was abrogated by mutation of the catalytic site residues. L. pneumophila triggers the reduction of several sphingolipids critical for macrophage function in an LpSpl-dependent and independent manner. LpSpl activity alone was sufficient to prevent an increase in sphingosine levels in infected host cells and to inhibit autophagy during macrophage infection. LpSpl was required for efficient infection of A/J mice, highlighting an important virulence role for this effector. Thus, we have uncovered a previously unidentified mechanism used by intracellular pathogens to inhibit autophagy, namely the disruption of host sphingolipid biosynthesis. PMID- 26831116 TI - Physiological state gates acquisition and expression of mesolimbic reward prediction signals. AB - Phasic dopamine signaling participates in associative learning by reinforcing associations between outcomes (unconditioned stimulus; US) and their predictors (conditioned stimulus; CS). However, prior work has always engendered these associations with innately rewarding stimuli. Thus, whether dopamine neurons can acquire prediction signals in the absence of appetitive experience and update them when the value of the outcome changes remains unknown. Here, we used sodium depletion to reversibly manipulate the appetitive value of a hypertonic sodium solution while measuring phasic dopamine signaling in rat nucleus accumbens. Dopamine responses to the NaCl US following sodium depletion updated independent of prior experience. In contrast, prediction signals were only acquired through extensive experience with a US that had positive affective value. Once learned, dopamine prediction signals were flexibly expressed in a state-dependent manner. Our results reveal striking differences with respect to how physiological state shapes dopamine signals evoked by outcomes and their predictors. PMID- 26831118 TI - Ribbon curling via stress relaxation in thin polymer films. AB - The procedure of curling a ribbon by running it over a sharp blade is commonly used when wrapping presents. Despite its ubiquity, a quantitative explanation of this everyday phenomenon is still lacking. We address this using experiment and theory, examining the dependence of ribbon curvature on blade curvature, the longitudinal load imposed on the ribbon, and the speed of pulling. Experiments in which a ribbon is drawn steadily over a blade under a fixed load show that the ribbon curvature is generated over a restricted range of loads, the curvature/load relationship can be nonmonotonic, and faster pulling (under a constant imposed load) results in less tightly curled ribbons. We develop a theoretical model that captures these features, building on the concept that the ribbon under the imposed deformation undergoes differential plastic stretching across its thickness, resulting in a permanently curved shape. The model identifies factors that optimize curling and clarifies the physical mechanisms underlying the ribbon's nonlinear response to an apparently simple deformation. PMID- 26831117 TI - Sensor histidine kinase is a beta-lactam receptor and induces resistance to beta lactam antibiotics. AB - beta-Lactams disrupt bacterial cell wall synthesis, and these agents are the most widely used antibiotics. One of the principle mechanisms by which bacteria resist the action of beta-lactams is by producing beta-lactamases, enzymes that degrade beta-lactams. In Gram-negative bacteria, production of beta-lactamases is often induced in response to the antibiotic-associated damage to the cell wall. Here, we have identified a previously unidentified mechanism that governs beta lactamase production. In the Gram-negative enteric pathogen Vibrio parahaemolyticus, we found a histidine kinase/response regulator pair (VbrK/VbrR) that controls expression of a beta-lactamase. Mutants lacking either VbrK or VbrR do not produce the beta-lactamase and are no longer resistant to beta-lactam antibiotics. Notably, VbrK autophosphorylation is activated by beta-lactam antibiotics, but not by other lactams. However, single amino acid substitutions in the putative periplasmic binding pocket of VbrK leads its phosphorylation in response to both beta-lactam and other lactams, suggesting that this kinase is a beta-lactam receptor that can directly detect beta-lactam antibiotics instead of detecting the damage to cell wall resulting from beta-lactams. In strong support of this idea, we found that purified periplasmic sensor domain of VbrK binds penicillin, and that such binding is critical for VbrK autophosphorylation and beta-lactamase production. Direct recognition of beta-lactam antibiotics by a histidine kinase receptor may represent an evolutionarily favorable mechanism to defend against beta-lactam antibiotics. PMID- 26831119 TI - Effect of transtympanic betamethasone delivery to the inner ear. AB - To investigate the effect of transtympanic betamethasone administration on hearing function with histologic correlation, rats were divided into three transtympanic treatment groups: isotonic saline (group I, n = 10), gentamicin (group II, n = 10) and betamethasone (group III, n = 10). Distortion product otoacoustic emission thresholds were compared on day 10. Also histological effects on cellular apoptosis in both the inner and outer hair cells in organ of Corti and spiral ganglion neurons were evaluated. Distortion product otoacoustic emission thresholds were comparable (p > 0.05) between group I and group III in all measurements. Distortion product otoacoustic emission thresholds of group II were significantly elevated in all measurements when compared with group I (p < 0.05) and group III (p < 0.05). In the Terminal deoxynucleotidyl transferase dUTP Nick End Labelling (TUNEL), Caspase-3, Caspase-8 and Caspase-9 staining method the amount of apoptotic cells in group II were significantly elevated in all measurements compared with group I (p < 0.05). In the TUNEL staining method the amount of apoptotic cells in Group III were significantly elevated compared with group I in both the organ of Corti and spiral ganglion neurons (p < 0.05). The overall histological results revealed that the severity of cellular apoptosis caused by betamethasone was somewhere between isotonic saline and gentamicin. Transtympanic betamethasone does not affect inner ear function as measured by distortion product otoacoustic emission responses, but some increase in cellular apoptosis in the organ of Corti and spiral ganglion neurons was observed. These findings suggest that transtympanic betamethasone may have mild ototoxic effects. Further studies are needed to obtain precise results for transtympanic application of betamethasone. PMID- 26831121 TI - AlPd15B7: a new superconducting cage-compound with an anti-Yb3Rh4Sn13-type of structure. AB - A new intermetallic compound AlPd15B7 was synthesized by arc-melting the stoichiometric mixture of the elements. Single crystal X-ray diffraction data of ternary metal-rich boride reveal a new type of structure with the space group Ia3d and the lattice parameter a = 16.4466(3) A. It adopts a filled anti Yb3Rh4Sn13-type structure, where the positions corresponding to 3Yb, 4Rh and 13Sn atoms are occupied by 3Pd, 4B, and 1Al + 12 Pd, respectively and 3B additionally at interstitial sites. Magnetic susceptibility, electrical resistivity, and specific heat measurements reveal bulk superconductivity with a critical temperature Tc ~ 2.9 K. Electronic structure calculations show that Pd 4d and B 2p states dominate the density of states (DOS) at the Fermi level EF. PMID- 26831120 TI - Association between sleep quality and psychiatric disorders in patients with subjective tinnitus in China. AB - The study aimed to investigate the relationship between quality of sleep and psychiatric disorders including anxiety and depression in patients with subjective tinnitus. Early intervention is associated with improved therapeutic outcomes. We used Pittsburgh sleep quality index (PSQI), self-rating anxiety scale (SAS), self-rating depression scale (SDS) and tinnitus handicap inventory (THI) in 543 patients [224 male (41.3 %); 319 female (58.7 %)] with subjective tinnitus enrolled in the ENT outpatient clinic from 2013 to 2015. Tinnitus characteristics and hearing status were recorded. A binary step-wise logistic regression analysis was performed. Two hundred cases (36.8 %) including 65 men (32.5 %) and 135 women (67.5 %) were diagnosed with sleep disorders. The PSQI score was the highest in patients with anxiety plus depression. Prolonged sleep latency and daytime dysfunction were positively associated with anxiety and depression. Increased sleep latency score was associated with 1.521- and 1.667 fold increased risk of anxiety and depression. Increase in the daytime dysfunction score was associated with 1.941- and 1.477-fold increases in the risk of anxiety and depression, respectively. Psychiatric and sleep disorders are highly prevalent in patients with subjective tinnitus. The most severe sleep impairment was found in patients with anxiety plus depression, resulting from prolonged sleep latency and severe daytime dysfunction. Acute duration, young people, hearing loss, impaired sleep, and severity of tinnitus were the major risk factors for tinnitus accompanied with anxiety symptoms. Severity of tinnitus and sleep impairment appeared to be the major risk factors of tinnitus accompanied with depression symptoms. PMID- 26831122 TI - Effects of Metformin and Exercise Training, Alone or in Combination, on Cardiac Function in Individuals with Insulin Resistance. AB - INTRODUCTION: In patients affected by insulin resistance (IR), metformin (MET) therapy has been shown to exert its positive effects by improving glucose tolerance and preventing the evolution to diabetes. Recently, it was shown that the addition of metformin to physical training did not improve sensitivity to insulin or peak oxygen consumption (peak VO2). The purpose of this study was to establish the effect of metformin and exercise, separately or in combination, on systolic left ventricular (LV) function in individuals with IR. METHODS: Seventy five patients with IR were enrolled and subsequently assigned to MET, combination MET and exercise, or exercise alone. The LV systolic and diastolic functions were evaluated with standard echocardiography tissue Doppler imaging (TDI) and speckle tracking echocardiography at baseline and after 12 weeks of treatment. RESULTS: MET, administered alone or in association with exercise, improved longitudinal LV function, as evidenced by an increase in systolic (S) wave on TDI, alongside increases in longitudinal global strain and strain rate in comparison to the group undergoing physical training alone. The traditional echocardiographic parameters showed no statistically significant differences among the three groups before or after the different cycles of therapy. CONCLUSIONS: Treatment with MET, either with or without exercise, but not exercise alone, produced a significant increase in global longitudinal LV systolic function at rest. These findings validate the observation that the use of MET alone or in association with exercise has a crucial role to counteract the negative effects of IR on cardiovascular function. PMID- 26831123 TI - Analysis of the factors influencing healthcare professionals' adoption of mobile electronic medical record (EMR) using the unified theory of acceptance and use of technology (UTAUT) in a tertiary hospital. AB - BACKGROUND: Although the factors that affect the end-user's intention to use a new system and technology have been researched, the previous studies have been theoretical and do not verify the factors that affected the adoption of a new system. Thus, this study aimed to confirm the factors that influence users' intentions to utilize a mobile electronic health records (EMR) system using both a questionnaire survey and a log file analysis that represented the real use of the system. METHODS: After observing the operation of a mobile EMR system in a tertiary university hospital for seven months, we performed an offline survey regarding the user acceptance of the system based on the Unified Theory of Acceptance and Use of Technology (UTAUT) and the Technology Acceptance Model (TAM). We surveyed 942 healthcare professionals over two weeks and performed a structural equation modeling (SEM) analysis to identify the intention to use the system among the participants. Next, we compared the results of the SEM analysis with the results of the analyses of the actual log files for two years to identify further insights into the factors that affected the intention of use. For these analyses, we used SAS 9.0 and AMOS 21. RESULTS: Of the 942 surveyed end users, 48.3 % (23.2 % doctors and 68.3 % nurses) responded. After eliminating six subjects who completed the survey insincerely, we conducted the SEM analyses on the data from 449 subjects (65 doctors and 385 nurses). The newly suggested model satisfied the standards of model fitness, and the intention to use it was especially high due to the influences of Performance Expectancy on Attitude and Attitude. Based on the actual usage log analyses, both the doctors and nurses used the menus to view the inpatient lists, alerts, and patients' clinical data with high frequency. Specifically, the doctors frequently retrieved laboratory results, and the nurses frequently retrieved nursing notes and used the menu to assume the responsibilities of nursing work. CONCLUSION: In this study, the end users' intentions to use the mobile EMR system were particularly influenced by Performance Expectancy and Attitude. In reality, the usage log revealed high frequency use of the functions to improve the continuity of care and work efficiency. These results indicate the influence of the factor of performance expectancy on the intention to use the mobile EMR system. Consequently, we suggest that when determining the implementation of mobile EMR systems, the functions that are related to workflow with ability to increase performance should be considered first. PMID- 26831124 TI - Differential effects of enalapril-felodipine versus enalapril-lercanidipine combination drug treatment on sympathetic nerve traffic and metabolic profile in obesity-related hypertension. AB - Scanty information is available on the effects of combination drug treatment based on an ACE inhibitor and a calcium channel blocker on the neurometabolic alterations characterizing obesity-related hypertension (OHT). After 2-week run in with enalapril (20 mg), 36 OHTs were randomized according to a double-blind crossover design to a combination therapy with either lercanidipine 10 mg (L) or felodipine extended release 5 mg (F), each lasting 8 weeks. Measurements included clinic and ambulatory blood pressure (BP) and heart rate, homeostasis model assessment index, plasma norepinephrine, and muscle sympathetic nerve activity. Patients with uncontrolled BP were then uptitrated to 20 mg/d (L) and 10 mg/d (F) combined with enalapril 20 mg, respectively, for further 8 weeks. For similar BP reductions, enalapril-lercanidipine (EL) caused norepinephrine and MSNA increases significantly less pronounced than those seen with enalapril-felodipine, the lesser sympathoexcitation observed with EL being coupled with a significant improvement in homeostasis model assessment index. This was the case also when L and F were uptitrated in the combination. In OHT, at variance from enalapril felodipine, EL combination is almost entirely devoid of any major sympathoexcitatory effect and is associated with an improvement in insulin sensitivity. PMID- 26831125 TI - Compliance with referrals to medical specialist care: patient and general practice determinants: a cross-sectional study. AB - BACKGROUND: In a gatekeeper system, primary care physicians and patients jointly decide whether or not medical specialist care is needed. However, it is the patient who decides to actually use the referral. Referral non-compliance could delay diagnosis and treatment. The objective of this study was to assess patient compliance with a referral to medical specialist care and identify patient and practice characteristics that are associated with it. METHODS: Observational study using data on 48,784 referrals to medical specialist care derived from electronic medical records of 58 general practices for the period 2008-2010. Referral compliance was based on claims data of medical specialist care. Logistic multilevel regression analyses were conducted to determine associations between patient and general practice characteristics and referral compliance. RESULTS: In 86.6% of the referrals, patients complied. Patient and not practice characteristics were significantly associated with compliance. Patients from deprived urban areas and patients aged 18-44 years were less likely to comply, whereas patients aged 65 years and older were more likely to comply. CONCLUSION: About 1 in 8 patients do not use their referral. These patients may not receive adequate care. Demographic and socio-economic factors appear to affect compliance. The results of this study may be used to make general practitioners more aware that some patients are more likely to be noncompliant with referrals. PMID- 26831126 TI - Early HIV treatment to forestall drug resistance. PMID- 26831128 TI - [Pulmonology in Lyon today]. PMID- 26831127 TI - Clinical, biochemical and molecular characterization of prosaposin deficiency. AB - Prosaposin (PSAP) deficiency is an ultra-rare, fatal infantile lysosomal storage disorder (LSD) caused by variants in the PSAP gene, with seven subjects reported so far. Here, we provide the clinical, biochemical and molecular characterization of two additional PSAP deficiency cases. Lysoplex, a targeted resequencing approach was utilized to identify the variant in the first patient, while quantification of plasma lysosphingolipids (lysoSLs), assessed by liquid chromatography mass spectrometry (LC-MS/MS) and brain magnetic resonance imaging (MRI), followed by Sanger sequencing allowed to attain diagnosis in the second case. Functional studies were carried out on patients' fibroblast lines to explore the functional impact of variants. The two patients were homozygous for two different truncating PSAP mutations (c.895G>T, p.Glu299*; c.834_835delGA, p.Glu278Aspfs*27). Both variants led to a complete lack of processed transcript. LC-MS/MS and brain MRI analyses consistently provided a distinctive profile in the two children. Quantification of specific plasma lysoSLs revealed elevated levels of globotriaosylsphingosine (LysoGb3) and glucosylsphingosine (GlSph), and accumulation of autophagosomes, due to a decreased autophagic flux, was observed. This report documents the successful use of plasma lysoSLs profiling in the PSAP deficiency diagnosis, as a reliable and informative tool to obtain a preliminary information in infantile cases with complex traits displaying severe neurological signs and visceral involvement. PMID- 26831129 TI - [Metastatic bronchial carcinoid tumors]. AB - Bronchial carcinoids are uncommon pulmonary neoplasms and represent 1 to 2 % of all lung tumors. In early stage of disease, the mainstay and only curative treatment is surgery. Bronchial carcinoids are generally regarded as low-grade carcinomas and metastatic dissemination is unusual. The management of the metastatic stage is not currently standardized due to a lack of relevant studies. As bronchial carcinoids and in particular their metastatic forms are rare, we apply treatment strategies that have been evaluated in gastrointestinal and pancreatic neuroendocrine tumors. However, bronchial carcinoids have their own characteristic. A specific therapeutic feature of these metastatic tumors is that they require a dual approach: both anti-secretory for the carcinoid syndrome, and anti-tumoral. PMID- 26831130 TI - Preface. PMID- 26831131 TI - Pediatric surgery as an essential component of global child health. AB - Recent initiatives in global health have emphasized universal coverage of essential health services. Surgical conditions play a critical role in child health in resource-poor areas. This article discusses (1) the spectrum of pediatric surgical conditions and their treatment; (2) relevance to recent advances in global surgery; (3) challenges to the prioritization of surgical care within child health, and possible solutions; (4) a case example from a resource poor area (Uganda) illustrating some of these concepts; and (5) important child health initiatives with which surgical services should be integrated. Pediatric surgery providers must lead the effort to prioritize children's surgery in health systems development. PMID- 26831133 TI - Congenital anomalies in the context of global surgery. AB - Surgery is increasingly recognized as an essential component of global health development. This article will review the state of global pediatric surgery, utilizing congenital anomalies as a framework in which to discuss the promise of pediatric surgery in reducing the global burden of disease. Congenital anomalies are responsible for a substantial burden of morbidity and mortality in low- and middle-income countries (LMICs), as well as significant emotional and economic harms to the families of children with congenital anomalies. Limited pediatric surgical capacity in many LMICs has culminated in a devastating burden of avertable disability and death. Pediatric surgery is an effective and cost effective means to reduce this burden. Pediatric surgeons must continue to drive the growth of global pediatric surgery by engaging in clinical practice, educational partnerships, and research initiatives. PMID- 26831132 TI - Financing pediatric surgery in low-, and middle-income countries. AB - Congenital anomalies once considered fatal, are now surgically correctable conditions that now allow children to live a normal life. Pediatric surgery, traditionally thought of as a privilege of the rich, as being too expensive and impractical, and which has previously been overlooked and excluded in resource poor settings, is now being reexamined as a cost-effective strategy to reduce the global burden of disease-particularly in low, and middle-income countries (LMICs). However, to date, global pediatric surgical financing suffers from an alarming paucity of data. To leverage valuable resources and prioritize pediatric surgical services, timely, accurate and detailed global health spending and financing for pediatric surgical care is needed to inform policy making, strategic health-sector budgeting and resource allocation. This discussions aims to characterize and highlight the evidence gaps that currently exist in global financing and funding flow for pediatric surgical care in LMICs. PMID- 26831134 TI - Caring for the injured child in settings of limited resource. AB - Children represent the most vulnerable members of our global society, a truth that is magnified when they are physically wounded. In much of the developed world, society has responded by offering protection in the form of law, injury prevention guidelines, and effective trauma systems to provide care for the injured child. Much of our world, though, remains afflicted by poverty and a lack of protective measures. As the globe becomes smaller by way of ease of travel and technology, surgeons are increasingly able to meet these children where they live and in doing so offer their hands and voices to care and protect these young ones. This article is intended as an overview of current issues in pediatric trauma care in the developing world as well as to offer some tips for the volunteer surgeon who may be involved in the care of the injured child in a setting of limited resource availability. PMID- 26831135 TI - Injuries and surgical needs of children in conflict and disaster: From Boston to Haiti and beyond. AB - Comprehensive care of patients in conflict and disaster requires coordination of medical, social, and public health agencies. Pediatric patients in these settings comprise a particularly vulnerable group subject to disruption of social networks and separation from family, inadequate surgical care due to lack of surgeon, anesthetist, and nursing specialization, and a general lack of advocacy within the global public health agenda. In the recent upswell of attention to the global surgical burden of disease and deficiencies in necessary infrastructure, the needs of pediatric surgical patients remain underappreciated and underemphasized amid calls for improvement in global surgical health. Experience in recent natural and man-made disasters has demonstrated that pediatric patients makeup a significant proportion of those injured, and has perhaps refocused our need to better characterize the surgical needs of children in conflict and disaster. In addition to treat such patients, we recognize the unmet challenges of improving pediatric emergency and surgical infrastructures in the low- and middle-income country settings where conflict and disaster occur most often, and continuing to advocate for vulnerable children worldwide and keep them out of harm's way. PMID- 26831136 TI - The pediatric surgery workforce in low- and middle-income countries: problems and priorities. AB - Most of the world is in a surgical workforce crisis. While a lack of human resources is only one component of the myriad issues affecting surgical care in resource-poor regions, it is arguably the most consequential. This article examines the current state of the pediatric surgical workforce in low- and middle income countries (LMICs) and the reasons for the current shortfalls. We also note progress that has been made in capacity building and discuss priorities going forward. The existing literature on this subject has naturally focused on regions with the greatest workforce needs, particularly sub-Saharan Africa (SSA). However, wherever possible we have included workforce data and related literature from LMICs worldwide. The pediatric surgeon is of course critically dependent on multi-disciplinary teams. Surgeons in high-income countries (HICs) often take for granted the ready availability of excellent anesthesia providers, surgically trained nurses, radiologists, pathologists, and neonatologists among many others. While the need exists to examine all of these disciplines and their contribution to the delivery of surgical services for children in LMICs, for the purposes of this review, we will focus primarily on the role of the pediatric surgeon. PMID- 26831137 TI - Developing pediatric surgery in low- and middle-income countries: An evaluation of contemporary education and care delivery models. AB - There are several different models of education and care delivery models in low- and middle-income countries (LMICs), and many endeavors combine more than one of the described models. This article summarizes the burden of pediatric surgical disease and discusses the benefits and shortcomings of the following: faith-based missions; short-term surgical trips; partnerships, twinning, and academic collaborations; teaching workshops, "train the trainer," and pediatric surgery camps; specialty treatment centers; online conferences, telemedicine, and mobile health; specific programs for exchange and education; and training in high-income countries (HICs), fellowships, and observorships. It then addresses ethical concerns common to all humanitarian pediatric surgical efforts. PMID- 26831138 TI - An investment in knowledge: Research in global pediatric surgery for the 21st century. AB - The body of literature addressing surgical and anesthesia care for children in low- and middle-income countries (LMICs) is small. This lack of research hinders full understanding of the nature of many surgical conditions in LMICs and compromises potential efforts to alleviate the significant health, welfare and economic burdens surgical conditions impose on children, families and countries. This article will evaluate the need for improved global pediatric surgery research by (1) presenting the current state of surgical research for children in LMICs and (2) discussing methods and opportunities for improvement within the political context of current global health priorities. PMID- 26831139 TI - HIV/AIDS-related knowledge awareness and risk behaviors among injection drug users in Maanshan, China: a cross-sectional study. AB - BACKGROUND: Unsafe injection practices significantly increase the risk of human immunodeficiency virus (HIV) infection among injection drug users (IDUs). Little is known about how demographic characteristics of IDUs are linked to HIV-related risk behaviors in the central regions of China. METHODS: A cross-sectional survey was conducted at Mandatory Detoxification Centers (MDCs) and the community in Maanshan, China. RESULTS: Of the 916 IDUs, 96.4 % reported a history of heroin use during the past year, 93.4 % had HIV/AIDS knowledge, 16.8 % reported receptive syringe sharing and 12.2 % reported inconsistent condom use in commercial sex in the past year. Unsafe injection practice was associated with increased odds of minority ethnicity, lower level of education, and no peer education in the past year. Unsafe sex practice was associated with increased odds of being single, 18-30 years of age, non-local residence, and history of methamphetamine use in the past year. CONCLUSIONS: Integrated interventions to promote safe injection and protected commercial sex practices targeting IDUs must also consider individual and socio-environmental factors. PMID- 26831140 TI - Impact of HIV on mortality among patients treated for tuberculosis in Lima, Peru: a prospective cohort study. AB - BACKGROUND: Human immunodeficiency virus (HIV)-associated tuberculosis deaths have decreased worldwide over the past decade. We sought to evaluate the effect of HIV status on tuberculosis mortality among patients undergoing treatment for tuberculosis in Lima, Peru, a low HIV prevalence setting. METHODS: We conducted a prospective cohort study of patients treated for tuberculosis between 2005 and 2008 in two adjacent health regions in Lima, Peru (Lima Ciudad and Lima Este). We constructed a multivariate Cox proportional hazards model to evaluate the effect of HIV status on mortality during tuberculosis treatment. RESULTS: Of 1701 participants treated for tuberculosis, 136 (8.0%) died during tuberculosis treatment. HIV-positive patients constituted 11.0% of the cohort and contributed to 34.6% of all deaths. HIV-positive patients were significantly more likely to die (25.1 vs. 5.9%, P < 0.001) and less likely to be cured (28.3 vs. 39.4%, P = 0.003). On multivariate analysis, positive HIV status (hazard ratio [HR] = 6.06; 95% confidence interval [CI], 3.96-9.27), unemployment (HR = 2.24; 95% CI, 1.55 3.25), and sputum acid-fast bacilli smear positivity (HR = 1.91; 95% CI, 1.10 3.31) were significantly associated with a higher hazard of death. CONCLUSIONS: We demonstrate that positive HIV status was a strong predictor of mortality among patients treated for tuberculosis in the early years after Peru started providing free antiretroviral therapy. As HIV diagnosis and antiretroviral therapy provision are more widely implemented for tuberculosis patients in Peru, future operational research should document the changing profile of HIV-associated tuberculosis mortality. PMID- 26831142 TI - Hospitals are "gaming" data on common operations, leading surgeon says. PMID- 26831141 TI - The lived experience of Sjogren's Syndrome. AB - BACKGROUND: Sjogren's Syndrome is an autoimmune exocrinopathy characterised by lymphocytic infiltration of exocrine glands in multiple sites, with dry mouth as a primary presenting symptom. Although quantitative studies have shown the negative impact of both dry mouth and Sjogren's Syndrome on patients' quality of life, no qualitative diary and interview study has been undertaken to examine the lived experience of dry mouth for Sjogren's Syndrome sufferers. The aim of this qualitative study was to provide clinicians with insight into how dry mouth can impact on the daily lives of Sjogren's Syndrome patients. METHODS: The American European Consensus Group (AECG) Revised International Classification criteria were used to identify participants from patients seen in an oral medicine clinic. After pilot study work to test the approach, the 10 main study participants were recruited. Diary entries and semi-structured interviews were used to explore how dry mouth affects their lives. Owing to the exploratory nature of the research, thematic content analysis was applied, allowing the themes to arise naturalistically from the data without bias or elicitation. RESULTS: The data showed that it is unrealistic to understand the experience of a single symptom, but that the disease as a whole needs to be taken into perspective. The empirical evidence supported four main themes that depicted the lived experience of Sjogren's Syndrome. These included: (1) the journey to diagnosis; (2) disease impact spectrum (of dry mouth amid other symptoms); (3) interactions with healthcare professionals; and (4) the positive coping process. CONCLUSIONS: The findings revealed patients' perspectives on diagnosis, coping with dry mouth and Sjogren's Syndrome, and interaction with healthcare professionals. Dry mouth is not a trivial symptom for Sjogren's Syndrome sufferers; it has considerable impact on their day-to-day lives. Healthcare professionals need to understand patients as individuals in their environment in order to be part of the Sjogren's journey. PMID- 26831143 TI - Potential factors, including activities of daily living, influencing home discharge for patients with putaminal haemorrhage. AB - BACKGROUND: Convalescent rehabilitation wards assist stroke patients in acquiring skills for activities of daily living to increase the likelihood of home discharge. However, an improvement in activities of daily living does not necessarily imply that patients are discharged home. We investigated the characteristics of patients with putaminal haemorrhage who are discharged home following convalescence in rehabilitation wards. METHODS: The sample comprised 89 patients (58 men and 31 women) with putaminal haemorrhage hospitalised in the convalescent rehabilitation ward of our hospital between August 2012 and July 2013. Their age ranged from 29 to 88 years (61.9 +/- 11.9 years). The lesion occurred on the right side in 48 and on the left in 41 patients. The mean period from onset to hospitalisation in the convalescent rehabilitation ward was 30.8 +/ 17.2 days, and the mean hospitalisation period was 70.7 +/- 31.8 days. We examined age, sex, haematoma volume, duration from onset to hospitalisation, neurological symptoms, cognitive function, functional independence measure, number of cohabitating family members and whether the patient lived alone before stroke, and the relationship among these factors and discharge destination (home or facility/hospital) was assessed. RESULTS: The discharge destination was home for 71 and a facility or hospital for 18 patients. Differences were observed in age, haematoma volume, neurological symptoms, cognitive function, functional independence measure score on admission and discharge, number of cohabitating family members and whether the patient lived alone before stroke for patients discharged home. Patients who required long-term care and were discharged home were more likely to be living with family members who were present during daytime. Home discharge was possible if functional independence measure score was >=70 at the time of discharge for motor items and >=24 for cognitive items, even if a patient lived alone before stroke. CONCLUSIONS: Although the presence of cohabitating family members was important, the factor most strongly influencing home discharge was the patient's activities of daily living status at the time of discharge. For patients who lived alone before stroke, physical and cognitive functions must be maintained for them to be discharged home after rehabilitation. PMID- 26831144 TI - Altered cellular localization and hemichannel activities of KID syndrome associated connexin26 I30N and D50Y mutations. AB - BACKGROUND: Gap junctions facilitate exchange of small molecules between adjacent cells, serving a crucial function for the maintenance of cellular homeostasis. Mutations in connexins, the basic unit of gap junctions, are associated with several human hereditary disorders. For example, mutations in connexin26 (Cx26) cause both non-syndromic deafness and syndromic deafness associated with skin abnormalities such as keratitis-ichthyosis-deafness (KID) syndrome. These mutations can alter the formation and function of gap junction channels through different mechanisms, and in turn interfere with various cellular processes leading to distinct disorders. The KID associated Cx26 mutations were mostly shown to result in elevated hemichannel activities. However, the effects of these aberrant hemichannels on cellular processes are recently being deciphered. Here, we assessed the effect of two Cx26 mutations associated with KID syndrome, Cx26I30N and D50Y, on protein biosynthesis and channel function in N2A and HeLa cells. RESULTS: Immunostaining experiments showed that Cx26I30N and D50Y failed to form gap junction plaques at cell-cell contact sites. Further, these mutations resulted in the retention of Cx26 protein in the Golgi apparatus. Examination of hemichannel function by fluorescent dye uptake assays revealed that cells with Cx26I30N and D50Y mutations had increased dye uptake compared to Cx26WT (wild type) containing cells, indicating abnormal hemichannel activities. Cells with mutant proteins had elevated intracellular calcium levels compared to Cx26WT transfected cells, which were abolished by a hemichannel blocker, carbenoxolone (CBX), as measured by Fluo-3 AM loading and flow cytometry. CONCLUSIONS: Here, we demonstrated that Cx26I30N and D50Y mutations resulted in the formation of aberrant hemichannels that might result in elevated intracellular calcium levels, a process which may contribute to the hyperproliferative epidermal phenotypes of KID syndrome. PMID- 26831145 TI - Assessment of depression severity with the PHQ-9 in cancer patients and in the general population. AB - BACKGROUND: The Patient Health Questionnaire PHQ-9 is a widely used instrument to screen for depression in clinical research. The first aim of this study was to psychometrically test the PHQ-9 in a large sample of cancer patients. The second aim was to calculate unbiased estimates of the depression burden for several cancer groups taking into account age and gender distributions. METHODS: A sample of 2,059 cancer patients with varying diagnoses were examined in this study six months after discharge from a rehabilitation clinic. A representative sample of 2,693 people from the general population served as controls. Expected PHQ-9 mean scores of the general population sample, regressed on age and gender, were calculated to enable a fair comparison of different groups of cancer patients. RESULTS: While the reliability (Cronbach's alpha) for the PHQ-9 scale was good (alpha >= 0.84), the CFA fit indices of the one-dimensional solution were unsatisfactory in the patients' sample. The factorial analysis confirmed two factors. PHQ-9 mean scores for 15 types of cancer are given, ranging from 4.0 (prostate) to 8.2 (thyroid gland). Differences between expected mean scores (derived from the general population) and raw mean scores of the cancer subsamples are reported that provide a better estimate of the depression burden. CONCLUSIONS: The results confirmed that the PHQ-9 performs well in testing depression in cancer patients. Regression coefficients can be used for performing unbiased comparisons among cancer groups, not only for this study. The burden of patients with testis cancer and Hodgkin lymphoma is underestimated when age and gender are not taken into account. PMID- 26831146 TI - A mechanical evaluation of micro-HA/CS composite scaffolds with interconnected spherical macropores. AB - BACKGROUND: In the process of bone defective reparation and engineered bone tissue construction, osteoblasts are adhered to the surface of the scaffold materials and impart the external mechanical load to the osteoblasts. So, the dynamic mechanical property of the scaffolds play an important role in the bone tissue repair and it is valuable to research. Material type and the architectural design of scaffolds are also important to facilitate cell and tissue growth. The aim of this study was to prepare a kind of material with good pore connectivity and analyze its dynamic mechanical property. METHODS: Fabrication and characterization of micro-hydroxyapatite(m-HA)/chitosan(CS) polymer composite scaffolds with well interconnected spherical pore architectures were reports. Micro-HA was prepared by being calcined and ball milled. Paraffin spheres in the range of 160-330 um were fabricated with a dispersion method and used as the porogen in the fabrication of the scaffolds. Polymer scaffolds were fabricated by the technique of compression molding and particulate leaching method. The effects of the porogen content on the properties of the scaffolds were studied. RESULTS: With the increase of porogen, the pore of the scaffolds increased and became interconnected. Cyclic loading of three scaffolds were tested with 10 % strain under four levels of loading frequency, 0.1, 0.5, 1 and 1.5 Hz. The porous composite scaffolds exhibited a viscosity-elastic behaviour with a maximum stress of 3-4 kPa. At each frequency, modulus value is decreased with the paraffin microspheres content, but there was no significance difference in the peak stress of the three samples. All the samples tested displayed clear hysteresis loops. There was no significance difference in the peak hysteresis of the three samples, and the hysteresis difference values between the sixth compression cycle and the initial cycle for three samples was similar, with no statistically significant differences. CONCLUSIONS: Micro-HA/CS composite scaffolds with interconnected spherical macropores were fabricated using pherical paraffin as porogen. The porous composite scaffolds exhibited a viscosity-elastic behaviour with good repeatability. It is benefit to study the influence of the mechanical load on the cell of the scaffold. PMID- 26831147 TI - Ticks and rickettsiae from wildlife in Belize, Central America. AB - BACKGROUND: The agents of spotted fevers in Latin America are Rickettsia rickettsii, R. parkeri, Rickettsia sp. strain Atlantic rainforest, and R. massiliae. In Continental Central America, R. rickettsii remains the only known pathogenic tick-borne rickettsia. In the present study, ticks were collected from wild mammals in natural areas of Belize. Besides providing new data of ticks from Belize, we investigated rickettsial infection in some of these ticks. Our results provide ticks harboring rickettsial agents for the first time in Central America. METHODS: Between 2010 and 2015, wild mammals were lived-trapped in the tropical broadleaf moist forests of central and southern Belize. Ticks were collected from the animals and identified to species by morphological and molecular analysis (DNA sequence of the tick mitochondrial 16S RNA gene). Some of the ticks were tested for rickettsial infection by molecular methods (DNA sequences of the rickettsial gltA and ompA genes). RESULTS: A total of 84 ticks were collected from 8 individual hosts, as follows: Amblyomma pacae from 3 Cuniculus paca; Amblyomma ovale and Amblyomma coelebs from a Nasua narica; A. ovale from an Eira Barbara; A. ovale, Amblyomma cf. oblongoguttatum, and Ixodes affinis from a Puma concolor; and A. ovale, A. coelebs, A. cf. oblongoguttatum, and I. affinis from two Panthera onca. Three rickettsial agents were detected: Rickettsia amblyommii in A. pacae, Rickettsia sp. strain Atlantic rainforest in A. ovale, and Rickettsia sp. endosymbiont in Ixodes affinis. CONCLUSIONS: The present study provides unprecedented records of ticks harboring rickettsial agents in the New World. An emerging rickettsial pathogen of South America, Rickettsia sp. strain Atlantic rainforest, is reported for the first time in Central America. Besides expanding the distribution of 3 rickettsial agents in Central America, our results highlight the possible occurrence of Rickettsia sp. strain Atlantic rainforest-caused spotted fever human cases in Belize, since its possible vector, A. ovale, is recognized as one of the most important human-biting ticks in the Neotropical region. PMID- 26831148 TI - Better Communication for Better Public Health: Perspectives From an Interdisciplinary Training Program. AB - Myriad factors determine the health of young people-biological, psychological, familial, contextual, environmental, and political, to name a few. Improving the health of adolescents means that leaders in health care and public health must have the requisite skills for translating research into priorities, practices, and policies that influence a wide array of health determinants. While adolescent health training programs may give emphasis to effective communication with adolescents as patients or as priority populations in health education/promotion efforts, are we adequately preparing our future leaders with the skill sets necessary for moving scientific evidence into practice, programs, and policies? Internship and fellowship programs may invest heavily in teaching skills for conducting research and health education/promotion, but they may not focus enough on how to translate scientific evidence into practice, programs, and policy. In this commentary, we share our experiences equipping professionals working with adolescents in health care and public health settings with skills for scientific writing, public speaking, and advocacy on behalf of young people, and discuss the need for more collaboration across disciplines. PMID- 26831149 TI - Mobile Text Messaging and Adherence of Patients to Medication Prescriptions: A txt a dA keeps da doctR awA? PMID- 26831150 TI - Dopaminergic-induced dyskinesia assessment based on a single belt-worn accelerometer. AB - BACKGROUND: After several years of treatment, patients with Parkinson's disease (PD) tend to have, as a side effect of the medication, dyskinesias. Close monitoring may benefit patients by enabling doctors to tailor a personalised medication regimen. Moreover, dyskinesia monitoring can help neurologists make more informed decisions in patient's care. OBJECTIVE: To design and validate an algorithm able to be embedded into a system that PD patients could wear during their activities of daily living with the purpose of registering the occurrence of dyskinesia in real conditions. MATERIALS AND METHODS: Data from an accelerometer positioned in the waist are collected at the patient's home and are annotated by experienced clinicians. Data collection is divided into two parts: a main database gathered from 92 patients used to partially train and to evaluate the algorithms based on a leave-one-out approach and, on the other hand, a second database from 10 patients which have been used to also train a part of the detection algorithm. RESULTS: Results show that, depending on the severity and location of dyskinesia, specificities and sensitivities higher than 90% are achieved using a leave-one-out methodology. Although mild dyskinesias presented on the limbs are detected with 95% specificity and 39% sensitivity, the most important types of dyskinesia (any strong dyskinesia and trunk mild dyskinesia) are assessed with 95% specificity and 93% sensitivity. CONCLUSION: The presented algorithmic method and wearable device have been successfully validated in monitoring the occurrence of strong dyskinesias and mild trunk dyskinesias during activities of daily living. PMID- 26831151 TI - In vitro models for the study of osteoarthritis. AB - Osteoarthritis (OA) is a prevalent disease of most mammalian species and is a significant cause of welfare and economic morbidity in affected individuals and populations. In vitro models of osteoarthritis are vital to advance research into the causes of the disease, and the subsequent design and testing of potential therapeutics. However, a plethora of in vitro models have been used by researchers but with no consensus on the most appropriate model. Models attempt to mimic factors and conditions which initiate OA, or dissect the pathways active in the disease. Underlying uncertainty as to the cause of OA and the different attributes of isolated cells and tissues used mean that similar models may produce differing results and can differ from the naturally occurring disease. This review article assesses a selection of the in vitro models currently used in OA research, and considers the merits of each. Particular focus is placed on the more prevalent cytokine stimulation and load-based models. A brief review of the mechanism of these models is given, with their relevance to the naturally occurring disease. Most in vitro models have used supraphysiological loads or cytokine concentrations (compared with the natural disease) in order to impart a timely response from the cells or tissue assessed. Whilst models inducing OA-like pathology with a single stimulus can answer important biological questions about the behaviour of cells and tissues, the development of combinatorial models encompassing different physiological and molecular aspects of the disease should more accurately reflect the pathogenesis of the naturally occurring disease. PMID- 26831152 TI - 3D FSE Cube and VIPR-aTR 3.0 Tesla magnetic resonance imaging predicts canine cranial cruciate ligament structural properties. AB - Estimation of cranial cruciate ligament (CrCL) structural properties in client owned dogs with incipient cruciate rupture would be advantageous. The objective of this study was to determine whether magnetic resonance imaging (MRI) measurement of normal CrCL volume in an ex-vivo canine model predicts structural properties. Stifles from eight dogs underwent 3.0 Tesla 3D MRI. CrCL volume and normalized median grayscale values were determined using 3D Fast Spin Echo (FSE) Cube and Vastly under-sampled Isotropic PRojection (VIPR)-alternative repetition time (aTR) sequences. Stifles were then mechanically tested. After joint laxity testing, CrCL structural properties were determined, including displacement at yield, yield load, load to failure, and stiffness. Yield load and load to failure (R(2)=0.56, P <0.01) were correlated with CrCL volume determined by VIPR-aTR. Yield load was also correlated with CrCL volume determined by 3D FSE Cube (R(2)=0.32, P <0.05). Structural properties were not related to median grayscale values. Joint laxity and CrCL stiffness were not related to MRI parameters, but displacement at yield load was related to CrCL volume for both sequences during testing (R(2)>0.57, P <0.005). In conclusion, 3D MRI offers a predictive method for estimating canine CrCL structural properties. 3D MRI may be useful for monitoring CrCL properties in clinical trials. PMID- 26831153 TI - Can tail damage outbreaks in the pig be predicted by behavioural change? AB - Tail biting, resulting in outbreaks of tail damage in pigs, is a multifactorial welfare and economic problem which is usually partly prevented through tail docking. According to European Union legislation, tail docking is not allowed on a routine basis; thus there is a need for alternative preventive methods. One strategy is the surveillance of the pigs' behaviour for known preceding indicators of tail damage, which makes it possible to predict a tail damage outbreak and prevent it in proper time. This review discusses the existing literature on behavioural changes observed prior to a tail damage outbreak. Behaviours found to change prior to an outbreak include increased activity level, increased performance of enrichment object manipulation, and a changed proportion of tail posture with more tails between the legs. Monitoring these types of behaviours is also discussed for the purpose of developing an automatic warning system for tail damage outbreaks, with activity level showing promising results for being monitored automatically. Encouraging results have been found so far for the development of an automatic warning system; however, there is a need for further investigation and development, starting with the description of the temporal development of the predictive behaviour in relation to tail damage outbreaks. PMID- 26831154 TI - Skeletal muscle adaptations and muscle genomics of performance horses. AB - Skeletal muscles in horses are characterised by specific adaptations, which are the result of the natural evolution of the horse as a grazing animal, centuries of selective breeding and the adaptability of this tissue in response to training. These adaptations include an increased muscle mass relative to body weight, a great locomotor efficiency based upon an admirable muscle-tendon architectural design and an adaptable fibre-type composition with intrinsic shortening velocities greater than would be predicted from an animal of comparable body size. Furthermore, equine skeletal muscles have a high mitochondrial volume that permits a higher whole animal aerobic capacity, as well as large intramuscular stores of energy substrates (glycogen in particular). Finally, high buffer and lactate transport capacities preserve muscles against fatigue during anaerobic exercise. Many of these adaptations can improve with training. The publication of the equine genome sequence in 2009 has provided a major advance towards an improved understanding of equine muscle physiology. Equine muscle genomics studies have revealed a number of genes associated with elite physical performance and have also identified changes in structural and metabolic genes following exercise and training. Genes involved in muscle growth, muscle contraction and specific metabolic pathways have been found to be functionally relevant for the early performance evaluation of elite athletic horses. The candidate genes discussed in this review are important for a healthy individual to improve performance. However, muscle performance limiting conditions are widespread in horses and many of these conditions are also genetically influenced. PMID- 26831155 TI - Evaluation of a transcutaneous method to assess canine liver function by indocyanine green plasma disappearance rate in healthy adult Beagle dogs. AB - A non-invasive, transcutaneous method using near infrared spectroscopy to assess indocyanine green plasma disappearance rate (ICG-PDR) in healthy dogs subjected to different conditions was evaluated in eight healthy purpose-bred Beagles under isoflurane-anaesthesia (Trial 1) and when they had initially recovered from anaesthesia (Trial 2). Plasma ICG concentrations (0, 5, 10, 15, 30 min after rapid ICG injection (0.5 mg/kg) into a peripheral vein were determined by high performance liquid chromatography in parallel with transcutaneous measurements. ICG clearance (mL/min/kg) and retention rate after 15 min (R15, %) were calculated from plasma concentrations to be 3.09 +/- 0.83 (mean +/- SD) and 30.6 +/- 8.3 in anaesthetised dogs and 3.63 +/- 0.88 and 28.1 +/- 7.3 in recovering dogs, respectively. ICG-PDR (%/min) and R15 (%) obtained using the transcutaneous method were 7.11 +/- 3.18 and 34.6 +/- 12.4 (Trial 1) and 7.79 +/- 3.33 and 32.3 +/- 9.2 (Trial 2). The coefficients of determination (r(2)) for ICG clearance and ICG-PDR were 0.14 (Trial 1) and 0.81 (Trial 2) and 0.47 (Trial 1) and 0.29 (Trial 2) for R15, respectively. The mean bias (lower, upper limit of agreement) for R15 were 5.6 (-12.3, 23.5) (Trial 1) and 3.9 (-12.4, 20.1) (Trial 2). The results suggest good agreement between the two methods in dogs recovering from isoflurane anaesthesia and the transcutaneous method might be useful in real-time assessment of liver function in conscious dogs. PMID- 26831156 TI - The potential and limitations of quantitative electromyography in equine medicine. AB - This review discusses the scope of using (quantitative) electromyography (EMG) in diagnosing myopathies and neuropathies in equine patients. In human medicine, many EMG methods are available for the diagnosis, pathophysiological description and evaluation, monitoring, or rehabilitation of patients, and some of these techniques have also been applied to horses. EMG results are usually combined with other neurophysiological data, ultrasound, histochemistry, biochemistry of muscle biopsies, and clinical signs in order to provide a complete picture of the condition and its clinical course. EMG technology is commonly used in human medicine and has been subject to constant development and refinement since its introduction in 1929, but the usefulness of the technique in equine medicine is not yet widely acknowledged. The possibilities and limitations of some EMG applications for equine use are discussed. PMID- 26831157 TI - Tuberculoid nodular thelitis in a dairy goat flock. AB - An unusual outbreak of teat/udder skin lesions occurred in a dairy goat flock in France. Lesions first appeared as circular, indurated, erythematous areas of skin and progressed to form dark raised haemorrhagic crusts and ulcerative plaques. Histopathological examination revealed marked granulomatous dermatitis with multifocal ulceration. The granulomatous inflammation, with frequent Langhans type multinucleated cells and central caseous necrosis, was indicative of mycobacterial infection. The presence of non-cultivable mycobacteria was confirmed by sequencing PCR products from DNA extracted directly from the lesions and sequences matched a novel mycobacterial pathogen closely related to M. leprae and M. lepromatosis and previously identified in cattle thelitis. The association of nodular gross lesions and tuberculoid granulomas on the teat and lower udder, and the presence of mycobacteria DNA support a diagnosis of tuberculoid nodular thelitis in goats due to mycobacterial infection. PMID- 26831158 TI - Distribution of bovine herpesvirus type 1 in the nervous system of experimentally infected calves. AB - Bovine herpesvirus type 1 (BoHV-1) is responsible for respiratory and genital disease in cattle. BoHV-1 encephalitis is only occasionally reported. However, several cases of neurological disease have been recently attributed to BoHV-1. In this study, the distribution and pathological alterations caused by two BoHV-1 strains in the nervous system of experimentally infected calves during acute infection and reactivation are described. Calves were inoculated intranasally with BoHV-1 Los Angeles (BoHV-1.LA) or Cooper (BoHV-1.Cooper) strains. Acutely infected calves were euthanased at 6 days (BoHV-1.Cooper, n = 2) and 7 days post inoculation (BoHV-1.LA, n = 2). Latently infected calves that were given dexamethasone to induce reactivation were euthanased at 2 days (BoHV-1.Cooper, n = 2) or 5 days (BoHV-1.LA, n = 2) after dexamethasone administration. Both BoHV-1 strains were isolated from the brains of acutely infected calves. Distribution of viral DNA in the neural tissues was similar for both strains. During reactivation, neither BoHV-1.LA nor BoHV-1.Cooper was isolated from any brain section or trigeminal ganglia in infected calves. Macroscopic lesions were not evident in any group. In BoHV-1.LA infected calves, microscopic lesions were found in the brain but not in the trigeminal ganglia. Microscopic lesions in the brain of BoHV-1.Cooper infected calves were not as evident as in BoHV-1.LA infected animals. However, mononuclear infiltrates and neuronophagia were present in trigeminal ganglia. The results of this study demonstrated that respiratory BoHV-1 strains are able to replicate and disseminate within the bovine nervous tissue and provide evidence of the neuroinvasiveness of BoHV-1 strains. PMID- 26831159 TI - Effects of bovine subclinical mastitis caused by Corynebacterium spp. on somatic cell count, milk yield and composition by comparing contralateral quarters. AB - Subclinical mastitis caused by Corynebacterium spp. (as a group and at the species level) was investigated by evaluating contralateral (healthy and infected) mammary quarters for somatic cell count (SCC), milk yield and composition. Selection of cows with subclinical mastitis caused by Corynebacterium spp. was performed by microbiological culture of composite samples collected from 1242 dairy cows from 21 dairy herds. For each of the selected cows, milk yield was measured and milk samples were collected at the mammary quarter level (i.e., 1140 mammary samples collected from 285 cows) for analysis of milk composition and SCC. The identification of Corynebacterium spp. isolates was performed by 16S rRNA gene sequencing. One hundred and eighty Corynebacterium spp. isolates were identified, of which 167 (92.77%) were C.bovis and eight (4.44%) non-C.bovis; for five of the Corynebacterium spp. isolates (2.77%), sequencing of 16S rRNA genes did not allow identification at the species level. Mammary quarters infected with Corynebacterium spp. as a group had a higher geometric mean SCC (197,900 cells/mL) than healthy contralateral mammary quarters (85,800 cells/mL). Species of Corynebacterium non-C.bovis were infrequently isolated and did not change SCC, milk yield or milk solid contents when evaluated at the contralateral quarter level. Although C.bovis infection showed no effect on milk yield, fat, protein, casein or total solids in milk, it increased SCC and decreased lactose and milk solids non-fat content. PMID- 26831160 TI - Identification of Brucella ovis exclusive genes in field isolates from Argentina. AB - Brucellosis caused by Brucella ovis is one of the most important infectious diseases of sheep. The aim of this study was to determine the presence of genes both inside and outside the specific B. ovis pathogenicity island 1 (BOPI-1) in a large collection of field isolates of B. ovis and other Brucella spp. from Argentina. The BOV_A0500 gene from B. ovis BOPI-1 was identified in all 104 B. ovis isolates studied. The BOPI-1 complete sequence was found to be conserved in 10 B. ovis strains from the collection, for which whole genome sequencing was performed. The BOV_0198 gene, which is outside BOPI-1 and considered exclusive to B. ovis, showed 90-100% identity with genomic regions of B. ovis, B. melitensis, B. abortus, B. canis, B. suis, B. microti, B. ceti and B. pinnipedialis. The results demonstrate that BOPI-1 is the only exclusive genetic region of B. ovis and marine Brucella spp. and that it is highly conserved in B. ovis field isolates from Argentina. PMID- 26831161 TI - Screening of virulence-associated genes as a molecular typing method for characterization of Streptococcus suis isolates recovered from wild boars and pigs. AB - Streptococcus suis is an important zoonotic pathogen associated with a wide range of diseases in pigs, but has also been isolated from wild animals such as rabbits and wild boars. In the current study, 126 S. suis isolates recovered from pigs (n = 85) and wild boars (n = 41) were tested by polymerase chain reaction (PCR) for the presence of nine virulence-associated genes. S. suis isolates from wild boars were differentiated by the lower detection rates of the epf, sly, mrp, sao and dltA genes (0%, 2.4%, 2.4%, 4.8% and 21.9%, respectively) compared with the isolates from pigs (56.5%, 75.3%, 56.5%, 88.2.0% and 88.2%, respectively). The differences in the content of these virulence-associated genes were statistically significant (P < 0.05). There was a correlation between the variants saoM and saoL and serotypes 2 and 9, respectively (P < 0.05). Isolates were classified into 31 virulence-associated gene profiles (VPs). Ten VPs were detected among wild boar isolates and 22 VPs among pig isolates, with only two VPs common to wild boars and pigs. The predominant VPs among isolates from wild boars (VP1, VP7) were different from those observed in pig isolates (VP16 and VP26). VP16 was detected exclusively in clinical pig isolates of serotype 9 and VP26 was detected in 71.4% of the serotype 2 clinical pig isolates. Further multilocus sequence typing (MLST) analysis showed a significant correlation association between certain VPs and STs (VP16 and VP17 with ST123 and ST125 and VP26 with ST1). In conclusion, the current study showed that combination of virulence-associated gene profiling and MLST analysis may provide more information of the relatedness of the S. suis strains from different animal species that could be useful for epidemiological purposes. PMID- 26831162 TI - Increased serum C-reactive protein concentrations in dogs with congestive heart failure due to myxomatous mitral valve disease. AB - Cardiovascular disease in humans and dogs is associated with mildly increased circulating concentrations of C-reactive protein (CRP). Few studies have evaluated associations between circulating CRP and canine myxomatous mitral valve disease (MMVD) and the results reported have been divergent. The aim of this study was to investigate whether serum concentrations of CRP, determined using a novel automated canine-specific high-sensitivity CRP assay (Gentian hsCRP), were associated with severity of MMVD and selected clinical variables in dogs. The study included 188 client-owned dogs with different severities of MMVD. Dogs were classified based on ACVIM consensus statement guidelines (group A, n = 58; group B1, n = 56; group B2, n = 38; group C, n = 36). Data were analysed using descriptive statistics and multiple regression analysis. Dogs with congestive heart failure (CHF; group C) had significantly higher CRP concentrations (median, 2.65 mg/L; quartile 1-quartile 3, 1.09-5.09) compared to dogs in groups A (median, 0.97 mg/L; quartile 1-quartile 3, <0.50-1.97; P = 0.001), B1 (median, 0.78 mg/L; quartile 1-quartile 3, <0.50-1.73, P <0.0001) and B2 (median, 0.60 mg/L; quartile 1-quartile 3, <0.50-1.23; P <0.0001). Other variables reflecting disease severity, including left atrial to aortic root ratio (P = 0.0002, adjusted r(2) = 0.07) and left ventricular end-diastolic diameter normalised for bodyweight (P = 0.0005, adjusted r(2) = 0.06), were positively associated with CRP concentration, but the association disappeared if dogs with CHF were excluded from analysis. In conclusion, slightly higher CRP concentrations were found in dogs with CHF whereas severity of asymptomatic MMVD showed no association with CRP concentrations. PMID- 26831163 TI - The benefits of growth monitoring in dairy heifers. PMID- 26831164 TI - Potential application of emerging diagnostic techniques to the diagnosis of bovine Johne's disease (paratuberculosis). AB - Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease (paratuberculosis), a chronic wasting disease in cattle with important welfare, economic and potential public health implications. Current tests are unable to recognise all stages of the disease, which makes it difficult to diagnose and control. This review explores emerging diagnostic techniques that could complement and enhance the diagnosis of MAP infection, including bacteriophage analysis, new MAP-specific antigens, host protein expression in response to infection, transcriptomic studies, analysis of microRNAs and investigation of the gastrointestinal microbiome. It emphasises the inherent challenges of diagnosing bovine Johne's disease and investigates novel areas which may have the potential both to advance our understanding of the immunopathology of MAP infection and to augment current diagnostic tests. PMID- 26831165 TI - A brighter future for dogs with immune-mediated haemolytic anaemia. PMID- 26831166 TI - Untangling the complexity of diseases such as calf diarrhoea is crucial to future productivity. PMID- 26831167 TI - Presence of neural progenitors in spontaneous canine gliomas: A histopathological and immunohistochemical study of 20 cases. AB - Gliomas are the most common primary brain tumours in humans and are associated with a poor prognosis. An accurate animal model of human glioma tumorigenesis is needed to test new treatment strategies. Dogs represent a promising model because they develop spontaneous diffusely-infiltrating gliomas. This study investigated whether spontaneous canine gliomas contain cancer stem cells previously identified in all grades of human gliomas. Twenty spontaneous cases of canine gliomas were graded according to the human WHO classification. The expression of different markers of lineage differentiation was evaluated with immunohistochemistry as follows: nestin and CD133 for neural stem cells, doublecortin for neuronal progenitor cells, Olig2 for glial progenitor cells, glial fibrillary acidic protein, vimentin and S-100 for mature glial cells, and NeuN and betaIII-tubulin for mature neurons. Gliomas were characterised as follows: five grade II (oligodendrogliomas); nine grade III (seven anaplastic oligodendrogliomas, one anaplastic astrocytoma, one anaplastic oligoastrocytoma); six grade IV (glioblastomas). Immunohistochemical evaluation revealed that (1) nestin and CD133 were expressed in all grades of gliomas with a higher proportion of positive cells in high-grade gliomas; (2) the expression of S-100 protein and Olig2 did not differ substantially between astrocytic and oligodendroglial tumours, and (3) all gliomas were negative for mature neuron markers. The results demonstrated the presence of undifferentiated neural progenitors in all grades of spontaneous canine gliomas, confirming the relevance of this animal model for further studies on cancer stem cells. PMID- 26831168 TI - Intravenous immunoglobulin transfusion in colostrum-deprived dairy calves. AB - Immunoglobulin transfusion is employed in the management of the failure of passive transfer (FPT). The aim of this study was to investigate the dose of immunoglobulin G (IgG) needed to reach a protective concentration (>10 g/L) in colostrum-deprived dairy calves. Twenty-eight Holstein Friesian newborn male calves were randomly assigned to either a control group (CG) or a treatment group (PG). Calves in the CG received 4 L of high quality colostrum within 12 h of birth. Calves in the PG received 62.7 +/- 3.1 g of IgG IV in 2.6 +/- 0.3 L of plasma within 6 h after birth. Serum immunoglobulin G (sIgG) and serum total protein (sTP) concentrations were assayed before and after (24 h, 72 h and 1 week after birth) plasma transfusion or colostrum ingestion. Serum (s) IgG and sTP concentrations increased in both groups throughout the period of observation. Mean sIgG and sTP concentrations after colostrum ingestion or plasma transfusion were higher in the CG than in the PG (P <0.01). Nine treated calves developed diarrhoea during the study and four were humanely euthanased due to progressive clinical deterioration. None of the calves in the CG showed signs of disease or died during the study. The dose of IgG used in this trial effectively provided an adequate sIgG concentration in colostrum-deprived calves (>10 g/L). Calves in the CG had significantly lower morbidity and mortality rates compared to those in the PG, suggesting that plasma transfusion alone is ineffective in providing complete protection against neonatal disease. PMID- 26831169 TI - Systematic pain assessment in horses. AB - Accurate recognition and quantification of pain in horses is imperative for adequate pain management. The past decade has seen a much needed surge in formal development of systematic pain assessment tools for the objective monitoring of pain in equine patients. This narrative review describes parameters that can be used to detect pain in horses, provides an overview of the various pain scales developed (visual analogue scales, simple descriptive scales, numerical rating scales, time budget analysis, composite pain scales and grimace scales), and highlights their strengths and weaknesses for potential clinical implementation. The available literature on the use of each pain assessment tool in specific equine pain states (laminitis, lameness, acute synovitis, post-castration, acute colic and post-abdominal surgery) is discussed, including any problems with sensitivity, reliability or scale validation as well as translation of results to other clinical pain states. The review considers future development and further refinement of currently available equine pain scoring systems. PMID- 26831170 TI - Evidence of intrauterine transmission of lumpy skin disease virus. AB - The current study describes the clinical, histopathological, molecular and serological diagnosis of lumpy skin disease (LSD) in a premature 1-day old calf that has been delivered from a cow that exhibited signs of LSD during the seventh month of pregnancy. The calf showed generalized skin lesions accompanied with signs of immaturity and died 36 h after birth. Postmortem and histopathological examinations revealed the involvement of multiple tissues. The presence of Neethling virus DNA in tissues was confirmed by polymerase chain reaction (PCR) and gene sequencing. Results of ELISA and serum neutralization test (SNT) confirmed that the calf had developed precolostral serum antibodies to LSD virus indicating in utero virus transmission. All tested sera collected from animals located in the same area were serologically positive, indicating exposure to LSD virus. PMID- 26831171 TI - Decreased expression of caspase-14 in an experimental model of canine atopic dermatitis. AB - Alterations in skin barrier function and filaggrin expression have been reported in atopic dermatitis (AD). Caspase-14, a protease important for filaggrin processing, is decreased in human AD. Atopic Beagle dogs with skin barrier alterations have been validated as model for AD. This study aimed to investigate caspase-14 in normal and atopic Beagle dogs. Skin biopsies from non-lesional and control skin were analyzed for caspase-14 by immunofluorescence. Six images/sections were blindly scored for intensity. Data were tested with unpaired Student's t test. A P value of <0.05 was considered significant. Caspase-14 was decreased in atopic compared to normal skin both quantitatively (P <0.001) and qualitatively (P = 0.006; agreement = 0.93; consistency = 0.94). In conclusion, caspase-14 is decreased in this model similarly to reports in humans, highlighting the relevance of filaggrin metabolic defects in AD. PMID- 26831172 TI - Infundibula of equine maxillary cheek teeth: Part 2: Morphological variations and pathological changes. AB - Incomplete cemental filling of the infundibula of equine maxillary cheek teeth (CT) is a common feature. Depending on the extent of the defect, three stages of infundibular decay have been suggested. However, histomorphological criteria to identify non-pathological abnormalities and destructive changes have not been defined. Six hundred and eighty eight CT with no evidence of dental diseases and 55 diseased permanent, fully erupted maxillary CT were evaluated on a macroscopic level by assessing the occlusal surface and horizontal sections, including porphyrin assays to detect residual blood within the infundibular cementum. Selected specimens were investigated on a microscopic level using routine and immunohistological staining methods to identify possible routes for the spread of infectious agents from the infundibulum into the endodontic system. Infundibular cemental hypoplasia was defined as a non-pathological developmental abnormality and was detected in >50% of CT with no evidence of dental diseases and in >70% of diseased CT. The first molar (Triadan 09) showed the highest prevalence (75%) of infundibular cemental hypoplasia. The mesial infundibulum was more often affected than the distal infundibulum. Infundibular erosion was considered as the most appropriate term to describe destructive infundibular changes. Infundibular erosion was present in <6% of CT with no evidence of dental diseases, but was detected in >27% of diseased teeth, always accompanied by endodontic disease. This suggests that teeth affected by infundibular cemental hypoplasia are prone to destructive erosion, which possibly leads to endodontic disease. Morphological factors that supplement this ethological hypothesis were described. In 74% of infundibula residual blood was identified, although no vital blood vessels were detected. It is assumed that this content of blood remained in the ample infundibular cemental blood system after tooth eruption and creates a favorable environment for microbial growth. The infundibular enamel was characterised by numerous infoldings to variable degrees and depths. In certain areas focal enamel aplasia was observed. These morphological features might contribute to microbiological settlement and spread of infectious agents through the infundibular wall into the endodontic system. PMID- 26831173 TI - The effect of loco-regional anaesthesia on motor activity induced by direct stimulation of the sciatic nerve in dogs. AB - A prospective, randomised, blinded, case-controlled clinical study was designed using client-owned dogs undergoing unilateral pelvic limb orthopaedic surgery, to determine the effect on induced motor activity by electrical stimulation of the sciatic nerve distal to the site of local anaesthetic administration. Dogs were administered 0.5% bupivacaine either extradurally or via a femoral and transgluteal sciatic electrolocation-guided nerve block prior to pelvic limb surgery. Motor response to electrical stimulation of branches of the sciatic nerve was tested and the minimum current required to induce muscle twitch was recorded prior to bupivacaine administration. Provided sensory blockade had been deemed successful intraoperatively, testing was repeated postoperatively, with each dog acting as its own control. Paired t-tests were performed to compare pre- and postoperative minimum currents. Eleven dogs administered extradural and 11 dogs administered femoral and sciatic perineural bupivacaine were eligible for post-operative testing. All dogs displayed normal motor response to electrical stimulation of the sciatic nerve at both sites tested before and after bupivacaine administration. There was no significant difference in the minimum current required to induce muscle twitch between pre- and post-operative testing (P = 0.31 sciatic site, P = 0.36 peroneal site), nor between the two groups using different loco-regional anaesthetic techniques (minimum P = 0.13). This study shows that stimulation of the sciatic nerve distal to the site of bupivacaine administration induces motor activity, despite adequate sensory blockade. This is relevant in surgical cases where mechanical stimulation of the sciatic nerve might be expected and needs to be recognised to avoid postoperative neurapraxia. PMID- 26831174 TI - Addition of magnesium sulphate to ropivacaine for spinal analgesia in dogs undergoing tibial plateau levelling osteotomy. AB - The aim of this blinded, randomised, prospective clinical trial was to determine whether the addition of magnesium sulphate to spinally-administered ropivacaine would improve peri-operative analgesia without impairing motor function in dogs undergoing orthopaedic surgery. Twenty client-owned dogs undergoing tibial plateau levelling osteotomy were randomly assigned to one of two treatment groups: group C (control, receiving hyperbaric ropivacaine by the spinal route) or group M (magnesium, receiving a hyperbaric combination of magnesium sulphate and ropivacaine by the spinal route). During surgery, changes in physiological variables above baseline were used to evaluate nociception. Arterial blood was collected before and after spinal injection, at four time points, to monitor plasma magnesium concentrations. Post-operatively, pain was assessed with a modified Sammarco pain score, a Glasgow pain scale and a visual analogue scale, while motor function was evaluated with a modified Tarlov scale. Assessments were performed at recovery and 1, 2 and 3 h thereafter. Fentanyl and buprenorphine were administered as rescue analgesics in the intra- and post-operative periods, respectively. Plasma magnesium concentrations did not increase after spinal injection compared to baseline. Group M required less intra-operative fentanyl, had lower Glasgow pain scores and experienced analgesia of longer duration than group C (527.0 +/- 341.0 min vs. 176.0 +/- 109.0 min). However, in group M the motor block was significantly longer, which limits the usefulness of magnesium for spinal analgesia at the investigated dose. Further research is needed to determine a clinically effective dose with shorter duration of motor block for magnesium used as an additive to spinal analgesic agents. PMID- 26831175 TI - Standing sedation with medetomidine and butorphanol in captive African elephants (Loxodonta africana). AB - Doses for standing sedation allowing for various procedures in otherwise inaccessible, untrained captive African elephant bulls are presented. Thirty three standing sedations were performed in 12 males aged 8-30 years (one to four sedations per animal). Each bull received a combination of 0.009 +/- 0.002 mg/kg medetomidine and 0.03 +/- 0.007 mg/kg butorphanol. Full sedation was reached on average 25.5 min after injection. The addition of hyaluronidase (1000-2000 IU) significantly reduced time to full sedation to 16.5 min (paired t test, P = 0.024). Reversal was induced with intramuscular atipamezole 0.008 (+/-0.002) and naltrexone 0.035 (+/-0.015) mg/kg. Recovery took on average 7 min (3-18 min). The medetomidine/butorphanol combination provided safe standing sedation for smaller procedures. PMID- 26831176 TI - Field study analysis of the influences of deworming regimens and housing conditions on parasites and sperm output in 21 European boar studs. AB - The current study reports the parasitological results of a quality control audit in 21 European boar studs. Field investigations were performed over a 2-year period (2012-2013) during the winter and spring. From each stud, an average of 30 (range, 25-33) individual faecal samples and ejaculates from 615 randomly selected Pietrain boars were analysed. Statistical analysis revealed a significant effect (P < 0.0001) of deworming regimen (DR) * age class of boar (A) and housing condition (H) * A on the presence of parasites. A second model indicated a significant effect (P = 0.0262) of DR * H * A on the presence of parasites. Sperm output was significantly affected (P < 0.0001) by the DR. Based on this study, recommendations for deworming AI boars are proposed. PMID- 26831177 TI - Lives worth living? Sheep welfare in the UK. PMID- 26831178 TI - Comparison of thermal and mechanical quantitative sensory testing in client-owned dogs with chronic naturally occurring pain and normal dogs. AB - Detecting dogs with central sensitization (CS) secondary to chronic pain is hampered by the current inability to measure this condition. The current study aimed to use quantitative sensory testing (QST) to measure (CS) in normal dogs and dogs with painful degenerative joint disease (DJD). It was hypothesized that QST would differ between these two groups of animals. Mechanical and thermal sensory thresholds obtained in animals with DJD-associated pain on two time points 28 days apart were compared with those of normal dogs. Values of sensory thresholds in DJD dogs obtained 28 days after the first evaluation were significantly lower than the results on the first day of evaluation but no differences were found when these results were compared with those of normal dogs. In conclusion, whether QST is different between dogs with chronic pain and normal dogs needs further investigation using a larger group of animals and age, weight and sex matched groups. PMID- 26831179 TI - Effect of repeated through-and-through joint lavage on serum amyloid A in synovial fluid from healthy horses. AB - The objective of this study was to evaluate the effect of through-and-through joint lavage on systemic and synovial serum amyloid A (SAA), total protein, nucleated cell count and percentage of neutrophils in the synovial fluid of six healthy horses. A prospective experimental study was performed where one healthy tarsocrural joint of each horse was randomly assigned to receive repeated through and-through joint lavage at 0, 48 and 96 h. Synovial fluid and blood samples were collected at 0 (baseline), 24, 48, 72, 96 and 120 h. Systemic and synovial SAA, total protein, nucleated cell count and percentage of neutrophils were measured and compared to baseline. Concentrations of systemic and synovial SAA percentage of neutrophils were not increased from baseline in contrast to total protein and nucleated cell counts (except for nucleated cell count at 96 h). In conclusion, repeated through-and-through joint lavage did not affect synovial SAA concentrations in horses; however, synovial total protein and nucleated cell count values increased. Some of the total protein and nucleated cell count values observed in this study were within the range reported for septic arthritis 24 h after joint lavage. Hence, synovial SAA may be a valuable marker to evaluate the clinical progression of septic joints after through-and-through joint lavage. Clinical studies evaluating synovial fluid SAA concentrations while treating synovial sepsis with through-and-through joint lavage are warranted. PMID- 26831180 TI - P2Y(1) receptors mediate purinergic relaxation in the equine pelvic flexure. AB - In the equine large intestine, the knowledge of the basic mechanisms underlying motility function is crucial to properly treat motility disorders. P2Y1 receptors are responsible for mediating purinergic colonic relaxation in several species. In vitro experimental studies of the circular muscle from the equine pelvic flexure (n = 6) were performed to characterize inhibitory and excitatory neuromuscular transmission. Electrophysiological studies showed that electrical field stimulation (EFS) evoked biphasic inhibitory junction potentials (IJPs) in smooth muscle cells: a fast IJP (IJPf) followed by a sustained IJP (IJPs). IJPs was sensitive to L-NNA 1 mM (a nitric oxide synthase inhibitor) (P <0.01), while IJPf was abolished by MRS2500 1 uM (a P2Y1 receptor antagonist) (P <0.001). EFS (5 Hz for 2 min) in the organ bath inhibited rhythmic contractions to 3.0 +/- 2.5% of basal area under the curve (P <0.0001). EFS under MRS2500 1 uM or L-NNA 1 mM incubation inhibited contractions to 6.0 +/- 2.8% (P <0.05) and 24.4 +/- 11.3% respectively (P <0.05). Combination of MRS2500 1 uM and L-NNA 1 mM completely reversed the EFS-induced inhibition of colonic motility. Non-nitrergic, non purinergic conditions were used to reveal voltage-dependent EFS-induced contractions sensitive to atropine 1 uM (P <0.001) and, therefore, cholinergic. In conclusion, nerve-mediated relaxation and contraction in the equine pelvic flexure involve the same mechanisms as those observed in the human colon. P2Y1 receptors mediate purinergic relaxations and are potential targets for the treatment of equine colonic motor disorders. PMID- 26831181 TI - Three-dimensional movements of the pelvis and the lumbar intervertebral joints in walking and trotting dogs. AB - Current knowledge of the physiological range of motion (ROM) in the canine axial system during locomotion is relatively limited. This is particularly problematic because dogs with back-related dysfunction frequently present for routine consultations. To collect detailed kinematic information and describe the three dimensional motions of the pelvis and the lumbar spine (i.e. intervertebral joints S1/L7-L2/L1), we recorded ventro-dorsal and latero-lateral X-ray videos of three walking and trotting dogs and reconstructed their pelvic and intervertebral motions using X-ray reconstruction of moving morphology and scientific rotoscoping. Pelvic roll displayed a monophasic motion pattern and the largest ROM with on average 13 degrees and 11 degrees during walking and trotting, respectively. Pelvic yaw had the smallest ROM with on average 5 degrees (walk) and 6 degrees (trot). A biphasic pattern was observed for pelvic pitch with a mean ROM of 8 degrees . At both gaits, the greatest intervertebral motions occurred either in S1/L7 or L7/L6. The intervertebral motions were mono- or biphasic in the horizontal and the transverse body planes and biphasic in the sagittal plane. Cranial to L6/5, the ROM tended to decrease from 3 degrees to <1.5 degrees in all three planes. Our results confirm that pelvic displacement and intervertebral joint movements are tightly linked with pelvic limb action at symmetrical gaits. The overall small movements, particularly cranial to L5, are consistent with the epaxial musculature globally stabilising the spine against the external and internal limb forces acting on the pelvis and the trunk during walking and trotting. PMID- 26831182 TI - Genetics: Divergence shapes recurrence. PMID- 26831183 TI - Prostate cancer: Personalized risk - stratified screening or abandoning it altogether? PMID- 26831184 TI - Haematological cancer: Ponatinib in CML - keeping PACE with multiple mutations. PMID- 26831186 TI - Salinity is the major factor influencing the sediment bacterial communities in a Mediterranean lagoonal complex (Amvrakikos Gulf, Ionian Sea). AB - Lagoons are naturally enriched habitats, with unstable environmental conditions caused by their confinement, shallow depth and state of saprobity. The frequent fluctuations of the abiotic variables cause severe changes in the abundance and distribution of biota. This relationship has been studied extensively for the macrofaunal communities, but not sufficiently so for the bacterial ones. The aim of the present study was to explore the biodiversity patterns of bacterial assemblages and to examine whether these patterns are associated with biogeographic and environmental factors. For this purpose, sediment samples were collected from five lagoons located in the Amvrakikos Gulf (Ionian Sea, Western Greece). DNA was extracted from the sediment and was further processed through 16S rRNA pyrosequencing. The results of this exploratory study imply that salinity is the environmental factor best correlated with the bacterial community pattern, which has also been suggested in similar studies but for macrofaunal community patterns. In addition, the bacterial community of the brackish lagoons is differentiated from that of the brackish-marine lagoons. The findings of this study indicate that the studied lagoons have distinct bacterial communities. PMID- 26831185 TI - Biological modelling of the radiation dose escalation effect of regional hyperthermia in cervical cancer. AB - BACKGROUND: Locoregional hyperthermia combined with radiotherapy significantly improves locoregional control and overall survival for cervical tumors compared to radiotherapy alone. In this study biological modelling is applied to quantify the effect of radiosensitization for three cervical cancer patients to evaluate the improvement in equivalent dose for the combination treatment with radiotherapy and hyperthermia. METHODS: The Linear-Quadratic (LQ) model extended with temperature-dependent LQ-parameters alpha and beta was used to model radiosensitization by hyperthermia and to calculate the conventional radiation dose that is equivalent in biological effect to the combined radiotherapy and hyperthermia treatment. External beam radiotherapy planning was performed based on a prescription dose of 46Gy in 23 fractions of 2Gy. Hyperthermia treatment using the AMC-4 system was simulated based on the actual optimized system settings used during treatment. RESULTS: The simulated hyperthermia treatments for the 3 patients yielded a T50 of 40.1 degrees C, 40.5 degrees C, 41.1 degrees C and a T90 of 39.2 degrees C, 39.7 degrees C, 40.4 degrees C, respectively. The combined radiotherapy and hyperthermia treatment resulted in a D95 of 52.5Gy, 55.5Gy, 56.9Gy in the GTV, a dose escalation of 7.3-11.9Gy compared to radiotherapy alone (D95 = 45.0-45.5Gy). CONCLUSIONS: This study applied biological modelling to evaluate radiosensitization by hyperthermia as a radiation-dose escalation for cervical cancer patients. This model is very useful to compare the effectiveness of different treatment schedules for combined radiotherapy and hyperthermia treatments and to guide the design of clinical studies on dose escalation using hyperthermia in a multi-modality setting. PMID- 26831187 TI - Liver fatty acid-binding protein may be a useful marker for non-alcoholic fatty liver disease but obesity is a major concern. PMID- 26831188 TI - Austrian recommendations on Targeted Hormone Therapy for metastatic, castration resistant prostate cancer. AB - In recent years, new therapeutic options have brought improvements in the treatment of metastatic, castration-resistant prostate cancer. Targeted Hormone Therapy (THT) represents a novel therapeutic component for which recent studies have shown a maximum benefit in the time between failure of androgen deprivation therapy (patient is metastatic and still pain-free) and prior to chemotherapy. Prostate cancer experts of the Austrian Society of Urology and Andrology (OGU), the Working Group for Urologic Oncology as part of the OGU, and the Professional Association of Austrian Urologists (BvU) have developed recommendations for the treatment of patients with asymptomatic or mildly symptomatic metastatic, castration-resistant prostate cancer. The definition of failure of classical hormonal therapy has been based on the guidelines of the German Society of Urology (Deutsche Gesellschaft fur Urologie, DGU) and the European Association of Urology (EAU). Criteria for the initiation of treatment with hormonal or chemotherapy include: Castration resistance with increase of prostate-specific antigen (PSA) Evidence of metastases in imaging No or mild symptoms Quality of Life Index of the Eastern Cooperative Oncology Group (ECOG) 0-1 (ECOG 2 requires individualized decision) [1]. Treatment should only be initiated when all of these four criteria are applicable, with the age of the patient being no exclusion criterion. First-line therapies for these patients include abiraterone, enzalutamide, and docetaxel as well as radium-223. The manuscript refers only to treatment regimens available in Austria.Selection of the initial treatment option starting with THT or chemotherapy-should be determined based on the individual patient characteristics. When using abiraterone or enzalutamide, re-staging within 3-6 months is recommended. PMID- 26831189 TI - Amyloid Neuropathy Following Domino Liver Transplantation: Response to Diflunisal. PMID- 26831190 TI - New Insights Into Mechanisms Associated With Angiotensin II-Induced Vascular Hypertrophy and Remodeling. PMID- 26831191 TI - Longitudinal Study of Left Ventricular Mass Growth: Comparative Study of Clinic and Ambulatory Systolic Blood Pressure in Chronic Kidney Disease. AB - Left ventricular (LV) hypertrophy is an established cardiovascular risk factor, yet little is known about its trajectory in people with chronic kidney disease. The goal of this prospective research study was to describe the trajectory of LV mass index, its relationship with blood pressure (BP), and specifically to compare the relationship of BP measured in the clinic and 24-hour ambulatory BP monitoring with LV mass index. Among 274 veterans with chronic kidney disease followed for over <= 4 years, the rate of growth of log LV mass index was inversely related to baseline LV mass index; it was rapid in the first 2 years, and plateaued subsequently. Systolic BP also significantly increased, but linearly, 1.7 mm Hg/y by clinic measurements and 1.8 mm Hg/y by 24-hour ambulatory BP. Cross-sectional and longitudinal associations of both clinic BP and 24-hour ambulatory BP with LV mass index were similar; both BP recording methods were associated with LV mass index and its growth over time. Controlled hypertension, masked uncontrolled hypertension, and uncontrolled hypertension categories had increasing LV mass index when diagnosed by 24-hour ambulatory and awake BP (P<0.05 for linear trend) but not sleep BP. After accounting for clinic BP both at baseline and longitudinally, LV mass index among individuals was additionally predicted by the difference in sleep systolic BP and clinic systolic BP (P=0.032). In conclusion, among people with chronic kidney disease, the growth of LV mass index is rapid. Research-grade clinic BP is useful to assess LV mass index and its growth over time. PMID- 26831192 TI - Evidence to Maintain the Systolic Blood Pressure Treatment Threshold at 140 mm Hg for Stroke Prevention: The Northern Manhattan Study. AB - In 2014, the Eighth Joint National Committee revised the target maximum systolic blood pressure (SBP) from 140 to 150 mm Hg in patients aged >=60 years without diabetes mellitus or chronic kidney disease. The evidence from cohort studies supporting this change was sparse, particularly among US minority populations. In the Northern Manhattan Study, 1750 participants aged >=60 years and free of stroke, diabetes mellitus, and chronic kidney disease had SBP measured at baseline and were annually followed up for incident stroke. Mean age at baseline was 72+/-8 years, 63% were women, 48% Hispanic, 25% non-Hispanic white, and 25% non-Hispanic black. Among all participants, 40% were on antihypertensive medications; 43% had SBP <140 mm Hg, 20% had 140 to 149 mm Hg, and 37% had >=150 mm Hg. Over a median follow-up of 13 years, 182 participants developed stroke. The crude stroke incidence was greater among individuals with SBP>=150 mm Hg (10.8 per 1000 person-years) and SBP 140 to 149 (12.3) than among those with SBP<140 (6.2). After adjusting for demographics, vascular risk factors, diastolic BP, and medication use, participants with SBP 140 to 149 mm Hg had an increased risk of stroke (hazard ratio, 1.7; 95% confidence interval, 1.2-2.6) compared with those with SBP <140 mm Hg. The increased stroke risk was most notable among Hispanics and non-Hispanic blacks. Raising the SBP threshold from 140 to 150 mm Hg as a new target for hypertension treatment in older individuals without diabetes mellitus or chronic kidney disease could have a detrimental effect on stroke risk reduction, especially among minority US populations. PMID- 26831193 TI - Placental Growth Factor Administration Abolishes Placental Ischemia-Induced Hypertension. AB - Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia because placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and vascular endothelial growth factor are both natural ligands for sFlt-1, vascular endothelial growth factor also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to 4 groups: normal pregnant or RUPP+/-infusion of recombinant human PlGF (180 MUg/kg per day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than normal pregnant rats. Infusion of recombinant human PlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that recombinant human PlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia. PMID- 26831194 TI - Roles of Caveolin-1 in Angiotensin II-Induced Hypertrophy and Inward Remodeling of Cerebral Pial Arterioles. AB - Angiotensin II (Ang II) is a major determinant of inward remodeling and hypertrophy in pial arterioles that may have an important role in stroke during chronic hypertension. Previously, we found that epidermal growth factor receptor is critical in Ang II-mediated hypertrophy that may involve caveolin-1 (Cav-1). In this study, we examined the effects of Cav-1 and matrix metalloproteinase-9 (MMP9) on Ang II-mediated structural changes in pial arterioles. Cav-1-deficient (Cav-1(-/-)), MMP9-deficient (MMP9(-/-)), and wild-type mice were infused with either Ang II (1000 ng/kg per minute) or saline via osmotic minipumps for 28 days (n=6-8 per group). Systolic arterial pressure was measured by a tail-cuff method. Pressure and diameter of pial arterioles were measured through an open cranial window in anesthetized mice. Cross-sectional area of the wall was determined histologically in pressurized fixed pial arterioles. Expression of Cav-1, MMP9, phosphorylated epidermal growth factor receptor, and Akt was determined by Western blotting and immunohistochemistry. Deficiency of Cav-1 or MMP9 did not affect Ang II-induced hypertension. Ang II increased the expression of Cav-1, phosphorylated epidermal growth factor receptor, and Akt in wild-type mice, which was attenuated in Cav-1(-/-) mice. Ang II-induced hypertrophy, inward remodeling, and increased MMP9 expression in pial arterioles were prevented in Cav-1(-/-) mice. Ang II-mediated increases in MMP9 expression and inward remodeling, but not hypertrophy, were prevented in MMP9(-/-) mice. In conclusion, Cav-1 is essential in Ang II-mediated inward remodeling and hypertrophy in pial arterioles. Cav-1 induced MMP9 is exclusively involved in inward remodeling, not hypertrophy. Further studies are needed to determine the role of Akt in Ang II-mediated hypertrophy. PMID- 26831195 TI - Acute Response to Unilateral Unipolar Electrical Carotid Sinus Stimulation in Patients With Resistant Arterial Hypertension. AB - Bilateral bipolar electric carotid sinus stimulation acutely reduced muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in patients with resistant arterial hypertension but is no longer available. The second-generation device uses a smaller unilateral unipolar disk electrode to reduce invasiveness while saving battery life. We hypothesized that the second-generation device acutely lowers BP and MSNA in treatment-resistant hypertensive patients. Eighteen treatment-resistant hypertensive patients (9 women/9 men; 53+/-11 years; 33+/-5 kg/m(2)) on stable medications have been included in the study. We monitored finger and brachial BP, heart rate, and MSNA. Without stimulation, BP was 165+/ 31/91+/-18 mm Hg, heart rate was 75+/-17 bpm, and MSNA was 48+/-14 bursts per minute. Acute stimulation with intensities producing side effects that were tolerable in the short term elicited interindividually variable changes in systolic BP (-16.9+/-15.0 mm Hg; range, 0.0 to -40.8 mm Hg; P=0.002), heart rate (-3.6+/-3.6 bpm; P=0.004), and MSNA (-2.0+/-5.8 bursts per minute; P=0.375). Stimulation intensities had to be lowered in 12 patients to avoid side effects at the expense of efficacy (systolic BP, -6.3+/-7.0 mm Hg; range, 2.8 to -14.5 mm Hg; P=0.028 and heart rate, -1.5+/-2.3 bpm; P=0.078; comparison against responses with side effects). Reductions in diastolic BP and MSNA (total activity) were correlated (r(2)=0.329; P=0.025). In our patient cohort, unilateral unipolar electric baroreflex stimulation acutely lowered BP. However, side effects may limit efficacy. The approach should be tested in a controlled comparative study. PMID- 26831196 TI - Prehypertension in Pregnancy and Risks of Small for Gestational Age Infant and Stillbirth. AB - It is not fully known whether maternal prehypertension is associated with increased risk of adverse fetal outcomes, and it is debated whether increases in blood pressure during pregnancy influence adverse fetal outcomes. We performed a population-based cohort study in nonhypertensive women with term (>=37 weeks) singleton births (n=157 446). Using normotensive (diastolic blood pressure [DBP] <80 mm Hg) women as reference, we calculated adjusted odds ratios with 95% confidence intervals between prehypertension (DBP 80-89 mm Hg) at 36 gestational weeks (late pregnancy) and risks of a small-for-gestational-age (SGA) birth or stillbirth. We further estimated whether an increase in DBP from early to late pregnancy affected these risks. We found that 11% of the study population had prehypertension in late pregnancy. Prehypertension was associated with increased risks of both SGA birth and stillbirth; adjusted odds ratios (95% confidence intervals) were 1.69 (1.51-1.90) and 1.70 (1.16-2.49), respectively. Risks of SGA birth in term pregnancy increased by 2.0% (95% confidence intervals 1.5-2.8) per each mm Hg rise in DBP from early to late pregnancy, whereas risk of stillbirth was not affected by rise in DBP during pregnancy. We conclude that prehypertension in late pregnancy is associated with increased risks of SGA birth and stillbirth. Risk of SGA birth was also affected by rise in DBT during pregnancy. Our findings provide new insight to the relationship between maternal blood pressure and fetal well-being and suggest that impaired maternal perfusion of the placenta contribute to SGA birth and stillbirth. PMID- 26831197 TI - Periostin Isoforms and Cardiac Remodeling After Myocardial Infarction: Is the Dispute Settled? PMID- 26831198 TI - Association of Higher Maternal Blood Pressure With Lower Infant Birthweight: Placental Cause or Cardiovascular Effect? PMID- 26831200 TI - Therapeutic improvements expected in the near future for schizophrenia and schizoaffective disorder: an appraisal of phase III clinical trials of schizophrenia-targeted therapies as found in US and EU clinical trial registries. AB - INTRODUCTION: In this review, the authors describe medications in phase III of clinical development for schizophrenia and schizoaffective disorder, and provide an opinion on how current treatment can be improved in the near future. AREAS COVERED: Recent (post 2013) phase III clinical trials of schizophrenia-targeted therapies were found in US and EU clinical trial registries. Two hundred fifty three trials were identified, that included 16 investigational compounds. The antipsychotics brexpiprazole and cariprazine have been approved in the US, and although both are dopamine D2 receptor partial agonists, they differ markedly in their pharmacodynamic profiles. Encenicline and valbenazine are first-in-class candidates for treatment of cognitive impairment associated with schizophrenia (CIAS) and tardive dyskinesia, respectively. Eleven add-on compounds were previously approved for other therapeutic indications and are for the most part being studied at academic medical centers and smaller pharmaceutical companies for negative symptoms and CIAS or for specific populations (comorbidities, antipsychotic-induced obesity). EXPERT OPINION: Promising new agents are emerging for schizophrenia and schizoaffective disorder. In addition to better-tolerated antipsychotics that treat positive symptoms, we could see the arrival of the first effective drug for negative symptoms and CIAS, which would strongly facilitate the ultimate goal of recovery in persons with schizophrenia. PMID- 26831202 TI - Hypersensitivity pneumonitis and antigen identification--An alternate approach. AB - OBJECTIVES: Identification of the causal antigen for patients with hypersensitivity pneumonitis (HP) is challenging in a standard clinical setting. The purpose of this pilot study was to determine whether it was possible to evaluate the home/workplace of patients, and identify the causal antigen. METHODS: Using a case-control study design we compared the presence of antibody to antigen collected in the environment of individuals with HP and controls consisting of family members/co-workers. Based on patient interviews, homes/workplaces were evaluated and suspected sources of antigen collected for use in immunoassays. RESULTS: Nineteen individuals with HP participated with 15 classified as having fibrotic disease. Up to 54 bulk samples were collected from each patient's environment, with multiple isolates (antigens) cultured from each. Of the seven individuals who tested positive to one or more environmental samples, three had a positive response to more than 1 antigen from the environmental sample (range 1-9). Twelve individuals tested positive to antigen(s) on a standard panel, with only one overlapping with the antigen from the home/workplace sample. A significant association existed between results of interviews/site evaluations, and ability to collect antigen eliciting a positive response (p < 0.001). CONCLUSION: Antigen identification was successful for patients with 'active' disease. Antigens for which patients test positive on standard panels may not be present in their environment. One benefit to patient centered testing is the ability to develop recommendations specific to their environment. As most individuals tested positive for >1 antigen, further investigation is warranted to determine the actual antigen responsible for disease. PMID- 26831203 TI - Association between obesity measures and albuminuria: A population-based study. AB - AIMS: The effects of obesity on the micro vascular diseases have drawn much attention. The aim of the study was to investigate the relationship between obesity measures and albuminuria in Chinese population. METHODS: We conducted a population-based cross-sectional study in 8600 subjects aged 40 years or older from a community in Guangzhou. Urinary albumin excretion and creatinine were measured and urinary albumin-to-creatinine ratio (ACR) was calculated as urinary albumin divided by creatinine. Low-grade albuminuria was classified as the highest quartile of ACR in participants without increased urinary albumin excretion. Increased urinary albumin excretion was defined according to the ACR ranges greater or equal than 30 mg/g. RESULTS: Pearson's correlation analysis and multivariate linear regression analysis revealed that body mass index (BMI), waist circumference and body fat content were significantly correlated with ACR (all P<0.01). Prevalence of low-grade albuminuria and increased urinary albumin excretion gradually increased across the BMI, waist circumference and body fat content quartiles (all P for trend<0.0001). Compared with participants in quartile 1 of BMI, waist circumference and body fat content, participants in quartile 4 had increased prevalence of low-grade albuminuria and increased urinary albumin excretion in logistic regression analysis after adjustment for age, sex, physical activity, fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol and HbA1c (all P<0.05). CONCLUSION: Obesity measures are associated with urinary albumin excretion in middle-aged and elderly Chinese. PMID- 26831204 TI - Type 2 diabetes mellitus and risk of hydrocephalus: A 5 year population-based follow-up study in Taiwan. AB - AIMS: Type 2 diabetes mellitus (T2DM) involves many organ systems and is associated with a wide range of neurologic complications. However, it is not known whether T2DM is a risk factor of hydrocephalus. METHODS: Research data were retrieved from the National Health Insurance Research Database of Taiwan. A total of 25,903 individuals with T2DM aged 40-80 years diagnosed during 2000-2003 and two times-number (n=51,806) age- and sex-matched comparisons during the same period were included. We tracked all individuals from their defined index visits for up to 5 years to detect a new diagnosis of hydrocephalus. RESULTS: Among the 25,903 patients, 9227 cases were newly diagnosed T2DM and 16,676 were pre existing T2DM patients. During the follow-up period, 27 (0.3%) of the newly diagnosed T2DM patients, 97 (0.6%) of the pre-existing T2DM patients and 149 (0.3%) of the comparison group developed hydrocephalus. The risk of hydrocephalus was significantly increased in patients with pre-existing diabetes but not in patients with newly diagnosed diabetes. CONCLUSIONS: Longer duration of type 2 diabetes is associated with an increased risk of the development of hydrocephalus. Further studies to confirm such association and to investigate the causality and mechanism are needed. PMID- 26831205 TI - Enhancement of oxidation resistance via a self-healing boron carbide coating on diamond particles. AB - A boron carbide coating was applied to diamond particles by heating the particles in a powder mixture consisting of H3BO3, B and Mg. The composition, bond state and coverage fraction of the boron carbide coating on the diamond particles were investigated. The boron carbide coating prefers to grow on the diamond (100) surface than on the diamond (111) surface. A stoichiometric B4C coating completely covered the diamond particle after maintaining the raw mixture at 1200 degrees C for 2 h. The contribution of the boron carbide coating to the oxidation resistance enhancement of the diamond particles was investigated. During annealing of the coated diamond in air, the priory formed B2O3, which exhibits a self-healing property, as an oxygen barrier layer, which protected the diamond from oxidation. The formation temperature of B2O3 is dependent on the amorphous boron carbide content. The coating on the diamond provided effective protection of the diamond against oxidation by heating in air at 1000 degrees C for 1 h. Furthermore, the presence of the boron carbide coating also contributed to the maintenance of the static compressive strength during the annealing of diamond in air. PMID- 26831206 TI - Corrigendum: Photon number statistics uncover the fluctuations in non-equilibrium lattice dynamics. PMID- 26831207 TI - Integrated Microfluidic Lectin Barcode Platform for High-Performance Focused Glycomic Profiling. AB - Protein glycosylation is one of the key processes that play essential roles in biological functions and dysfunctions. However, progress in glycomics has considerably lagged behind genomics and proteomics, due in part to the enormous challenges in analysis of glycans. Here we present a new integrated and automated microfluidic lectin barcode platform to substantially improve the performance of lectin array for focused glycomic profiling. The chip design and flow control were optimized to promote the lectin-glycan binding kinetics and speed of lectin microarray. Moreover, we established an on-chip lectin assay which employs a very simple blocking method to effectively suppress the undesired background due to lectin binding of antibodies. Using this technology, we demonstrated focused differential profiling of tissue-specific glycosylation changes of a biomarker, CA125 protein purified from ovarian cancer cell line and different tissues from ovarian cancer patients in a fast, reproducible, and high-throughput fashion. Highly sensitive CA125 detection was also demonstrated with a detection limit much lower than the clinical cutoff value for cancer diagnosis. This microfluidic platform holds the potential to integrate with sample preparation functions to construct a fully integrated "sample-to-answer" microsystem for focused differential glycomic analysis. Thus, our technology should present a powerful tool in support of rapid advance in glycobiology and glyco-biomarker development. PMID- 26831209 TI - Teaching and assessing ethics in the newborn ICU. AB - Ethics and professionalism education has become increasingly recognized as important and incorporated into graduate medical education. However, such education has remained largely unstructured and understudied in neonatology. Neonatal-perinatal fellowship training programs have generally grappled with how best to teach and assess ethics and professionalism knowledge, skills, and behavior in clinical practice, particularly in light of accreditation requirements, milestones, and competencies. This article reviews currently available teaching methods, pedagogy, and resources in medical ethics, professionalism, and communication, as well as assessment strategies and tools, to help medical educators and practicing clinicians ensure trainees achieve and maintain competency. The need for consensus and future research in these domains is also highlighted. PMID- 26831208 TI - Distinct Reward Properties are Encoded via Corticostriatal Interactions. AB - The striatum serves as a critical brain region for reward processing. Yet, understanding the link between striatum and reward presents a challenge because rewards are composed of multiple properties. Notably, affective properties modulate emotion while informative properties help obtain future rewards. We approached this problem by emphasizing affective and informative reward properties within two independent guessing games. We found that both reward properties evoked activation within the nucleus accumbens, a subregion of the striatum. Striatal responses to informative, but not affective, reward properties predicted subsequent utilization of information for obtaining monetary reward. We hypothesized that activation of the striatum may be necessary but not sufficient to encode distinct reward properties. To investigate this possibility, we examined whether affective and informative reward properties were differentially encoded in corticostriatal interactions. Strikingly, we found that the striatum exhibited dissociable connectivity patterns with the ventrolateral prefrontal cortex, with increasing connectivity for affective reward properties and decreasing connectivity for informative reward properties. Our results demonstrate that affective and informative reward properties are encoded via corticostriatal interactions. These findings highlight how corticostriatal systems contribute to reward processing, potentially advancing models linking striatal activation to behavior. PMID- 26831210 TI - Why Do Adolescents Self-Harm? AB - BACKGROUND: Given the high rates of self-harm among adolescents, recent research has focused on a better understanding of the motives for the behavior. AIMS: The present study had three aims: to investigate (a) which motives are most frequently endorsed by adolescents who report self-harm; (b) whether motives reported at baseline predict repetition of self-harm over a 6-month period; and (c) whether self-harm motives differ between boys and girls. METHOD: In all, 987 school pupils aged 14-16 years completed a lifestyle and coping questionnaire at two time points 6 months apart that recorded self-harm and the associated motives. RESULTS: The motive "to get relief from a terrible state of mind" was the most commonly endorsed reason for self-harm (in boys and girls). Interpersonal reasons (e.g., "to frighten someone") were least commonly endorsed. Regression analyses showed that adolescents who endorsed wanting to get relief from a terrible state of mind at baseline were significantly more likely to repeat self-harm at follow-up than those adolescents who did not cite this motive. CONCLUSION: The results highlight the complex nature of self-harm. They have implications for mental health provision in educational settings, especially in relation to encouraging regulation of emotions and help-seeking. PMID- 26831211 TI - Symptoms of Alcohol Dependence Predict Suicide Ideation Among Alaskan Undergraduates. AB - BACKGROUND: Previous research has demonstrated an association between alcohol related problems and suicidal ideation (SI). AIMS: The present study evaluated, simultaneously, alcohol consequences and symptoms of alcohol dependence as predictors of SI after adjusting for depressive symptoms and alcohol consumption. METHOD: A sample of 298 Alaskan undergraduates completed survey measures, including the Young Adult Alcohol Consequences Questionnaire, the Short Alcohol Dependence Data Questionnaire, and the Beck Depression Inventory - II. The association between alcohol problems and SI status was evaluated using sequential logistic regression. RESULTS: Symptoms of alcohol dependence (OR = 1.88, p < .05), but not alcohol-related consequences (OR = 1.01, p = .95), emerged as an independent predictor of SI status above and beyond depressive symptoms (OR = 2.39, p < .001) and alcohol consumption (OR = 1.08, p = .39). CONCLUSION: Alcohol dependence symptoms represented a unique risk for SI relative to alcohol-related consequences and alcohol consumption. Future research should examine the causal mechanism behind the relationship between alcohol dependence and suicidality among university students. Assessing the presence of dependence symptoms may improve the accuracy of identifying students at risk of SI. PMID- 26831212 TI - Psychosis and Suicide. AB - BACKGROUND: The life time risk of suicide among patients with long term psychosis is 5-15%. Suicide prevention in this group is a major clinical challenge. AIMS: To capture specific characteristics of suicidal communication and critical events preceding suicide in patients with psychosis. METHODS: Medical records were examined and a life event inventory applied to a one-year cohort of 21 cases of suicide in the clinical group in Stockholm county. RESULTS: In most cases direct or indirect verbal communication of suicidal thoughts were documented before the suicide. Three months preceeding death, 20 of the 21 subjects had described one or more negative critical experiences, typically physical illness, loss of contact with an important other, loss of "home", and intolerable side effects of medication. In most cases the suicide appeared to be the culmination of prolonged suffering and suicidal deliberations. CONCLUSIONS: Suicide prevention among patients with psychosis requires sensitivity, active listening, and responsiveness on the part of the care person to the patient's explicit suicidal communication and perceptions of care-related or other incidents or interactions, even when conveyed in an odd manner or with little emotion. To prevent suicide, attentive and long-term planning in collaboration with the patient is essential. PMID- 26831213 TI - MYPLAN - A Mobile Phone Application for Supporting People at Risk of Suicide. AB - BACKGROUND: Safety plans have been suggested as an intervention for people at risk of suicide. Given the impulsive character of suicidal ideation, a safety plan in the format of a mobile phone application is likely to be more available and useful than traditional paper versions. AIMS: The study describes MYPLAN, a mobile phone application designed to support people at risk of suicide by letting them create a safety plan. METHOD: MYPLAN was developed in collaboration with clinical psychiatric staff at Danish suicide preventive clinics. The mobile application lets the user create an individualized safety plan by filling in templates with strategies, actions, and direct links to contact persons. RESULTS: MYPLAN was developed in 2013 and is freely available in Denmark and Norway. It is designed for iPhone and android platforms. As of December 2015, the application has been downloaded almost 8,000 times. Users at risk of suicide as well as clinical staff have provided positive feedback on the mobile application. CONCLUSION: Support via mobile phone applications might be particularly useful for younger age groups at risk of suicide as well as in areas or countries where support options are lacking. Yet, it is important to examine the effectiveness of this type of intervention. PMID- 26831214 TI - Successful Treatment of Suicidal Risk. AB - BACKGROUND: In this article we focused on analyzing surveyed patient-generated responses based on two outcome questions derived from a suicide-specific framework called the Collaborative Assessment and Management of Suicidality (CAMS): Q1 - "Were there any aspects of your treatment that were particularly helpful to you? If so, please describe these. Be as specific as possible." Q2 - "What have you learned from your clinical care that could help you if you became suicidal in the future?" AIMS: To develop a reliable coding system based on formerly suicidal patients' responses to two open-ended prompts and examine most frequently identified themes. METHOD: The present study utilized a consensual qualitative research process to examine responses of clinically resolved suicidal patients, based on the CAMS resolution criteria (i.e., three consecutive CAMS sessions reporting the effective management of suicidal risk), to two Suicide Status Form (SSF) outcome questions (n = 49 for Q1, and n = 52 for Q2). RESULTS: Reliable coding systems were developed and used to determine major themes of successful patient responses. CONCLUSION: The results of this study provide insight into patients' experiences of a successful treatment for suicidal risk with larger implications for suicide-specific treatments in general. PMID- 26831215 TI - Singlet oxygen production in Chlamydomonas reinhardtii under heat stress. AB - In the current study, singlet oxygen formation by lipid peroxidation induced by heat stress (40 degrees C) was studied in vivo in unicellular green alga Chlamydomonas reinhardtii. Primary and secondary oxidation products of lipid peroxidation, hydroperoxide and malondialdehyde, were generated under heat stress as detected using swallow-tailed perylene derivative fluorescence monitored by confocal laser scanning microscopy and high performance liquid chromatography, respectively. Lipid peroxidation was initiated by enzymatic reaction as inhibition of lipoxygenase by catechol and caffeic acid prevented hydroperoxide formation. Ultra-weak photon emission showed formation of electronically excited species such as triplet excited carbonyl, which, upon transfer of excitation energy, leads to the formation of either singlet excited chlorophyll or singlet oxygen. Alternatively, singlet oxygen is formed by direct decomposition of hydroperoxide via Russell mechanisms. Formation of singlet oxygen was evidenced by the nitroxyl radical 2,2,6,6-tetramethylpiperidine-1-oxyl detected by electron paramagnetic resonance spin-trapping spectroscopy and the imaging of green fluorescence of singlet oxygen sensor green detected by confocal laser scanning microscopy. Suppression of singlet oxygen formation by lipoxygenase inhibitors indicates that singlet oxygen may be formed via enzymatic lipid peroxidation initiated by lipoxygenase. PMID- 26831216 TI - Ethnic Differences in Risk of Coronary Heart Disease in a Large Contemporary Population. AB - INTRODUCTION: Racial/ethnic differences in diabetes and cardiovascular disease are well documented, but disease estimates are often confounded by differences in access to quality health care. The objective of this study was to evaluate the ethnic differences in risk of future coronary heart disease in patient populations stratified by status of diabetes mellitus and prior coronary heart disease among those with uniform access to care in an integrated healthcare delivery system in Northern California. METHODS: A cohort was constructed consisting of 1,344,899 members with self-reported race/ethnicity, aged 30-90 years, and followed from 2002 through 2012. Cox proportional hazard regression models were specified to estimate race/ethnicity-specific hazard ratios for coronary heart disease (with whites as the reference category) separately in four clinical risk categories: (1) no diabetes with no prior coronary heart disease; (2) no diabetes with prior coronary heart disease; (3) diabetes with no prior coronary heart disease; and (4) diabetes with prior coronary heart disease. Analyses were performed in 2015. RESULTS: The median follow-up was 10 years (10,980,800 person-years). Compared with whites, blacks, Latinos, and Asians generally had lower risk of coronary heart disease across all clinical risk categories, with the exception of blacks with prior coronary heart disease and no diabetes having higher risk than whites. Findings were not substantively altered after multivariate adjustments. CONCLUSIONS: Identification of health outcomes in a system with uniform access to care reveals residual racial/ethnic differences and point to opportunities to improve health in specific subgroups and to improve health equity. PMID- 26831217 TI - Fluorescent/magnetic micro/nano-spheres based on quantum dots and/or magnetic nanoparticles: preparation, properties, and their applications in cancer studies. AB - The study of cancer is of great significance to human survival and development, due to the fact that cancer has become one of the greatest threats to human health. In recent years, the rapid progress of nanoscience and nanotechnology has brought new and bright opportunities to this field. In particular, the applications of quantum dots (QDs) and magnetic nanoparticles (MNPs) have greatly promoted early diagnosis and effective therapy of cancer. In this review, we focus on fluorescent/magnetic micro/nano-spheres based on QDs and/or MNPs (we may call them "nanoparticle-sphere (NP-sphere) composites") from their preparation to their bio-application in cancer research. Firstly, we outline and compare the main four kinds of methods for fabricating NP-sphere composites, including their design principles, operation processes, and characteristics (merits and limitations). The NP-sphere composites successfully inherit the unique fluorescence or magnetic properties of QDs or MNPs. Moreover, compared with the nanoparticles (NPs) alone, the NP-sphere composites show superior properties, which are also discussed in this review. Then, we summarize their recent applications in cancer research from three aspects, that is: separation and enrichment of target tumor cells or biomarkers; cancer diagnosis mainly through medical imaging or tumor biomarker detection; and cancer therapy via targeted drug delivery systems. Finally, we provide some perspectives on the future challenges and development trends of the NP-sphere composites. PMID- 26831218 TI - Heterogeneous Solvatochromism of Fluorescent DNA-Stabilized Silver Clusters Precludes Use of Simple Onsager-Based Stokes Shift Models. AB - The diverse optical and chemical properties of DNA-stabilized silver clusters (AgN-DNAs) have challenged the development of a common model for these sequence tunable fluorophores. Although correlations between cluster geometry and fluorescence color have begun to shed light on how the optical properties of AgN DNAs are selected, the exact mechanisms responsible for fluorescence remain unknown. To explore these mechanisms, we study four distinct purified AgN-DNAs in ethanol-water and methanol-water mixtures and find that the solvatochromic behavior of AgN-DNAs varies widely among different cluster species and differs markedly from prior results on impure material. Placing AgN-DNAs within the context of standard Lippert-Mataga solvatochromism models based on the Onsager reaction field, we show that such nonspecific solvent models are not universally applicable to AgN-DNAs. Instead, alcohol-induced solvatochromism of AgN-DNAs may be governed by changes in hydration of the DNA template, with spectral shifts resulting from cluster shape changes and/or dielectric changes in the local vicinity of the cluster. PMID- 26831219 TI - Differentially Methylated Genomic Regions in Birth-Weight Discordant Twin Pairs. AB - Poor nutrition during critical growth phases may alter the structural and physiologic development of vital organs thus "programming" the susceptibility to adult-onset diseases and disease-related health conditions. Epigenome-wide association studies have been performed in birth-weight discordant twin pairs to find evidence for such "programming" effects, but no significant results emerged. We further investigated this issue using a new computational approach: Instead of probing single genomic sites for significant alterations in epigenetic marks, we scan for differentially methylated genomic regions. Whole genome DNA methylation levels were measured in whole blood from 150 pairs of adult identical twins discordant for birth-weight. Intrapair differential DNA methylation was associated with qualitative (large or small) and quantitative (percentage) birth weight discordance at each genomic site using regression models adjusting for age and sex. Based on the regression results, genomic regions with consistent alteration patterns of DNA methylation were located and tested for significant robustness using computational permutation tests. This yielded an interesting genomic region on chromosome 1, which is significantly differentially methylated for quantitative birth-weight discordance. The region covers two genes (TYW3 and CRYZ) both reportedly associated with metabolism. We conclude that prenatal conditions for birth-weight discordance may result in persistent epigenetic modifications potentially affecting even adult health. PMID- 26831221 TI - Epidemiology of shoulder and elbow pain in youth baseball players. AB - OBJECTIVES: There are relatively few published epidemiological studies examining the differences in the risk of shoulder and elbow pain in young baseball players. The purpose of this study was to investigate risk factors for shoulder and elbow pain in child and adolescent baseball players. METHODS: A total of 1563 players aged 7 to 12 years participated in this investigation. Subjects were asked whether they had experienced episodes of shoulder or elbow pain. We investigated the following risk factors for shoulder and elbow pain: age, position, years of baseball experience, and training hours per week. Data from the groups with and without shoulder and elbow pain were analyzed using multivariate logistic regression models. RESULTS: Among the 1563 participants, 15.9% and 29.2% reported episodes of shoulder and elbow pain, respectively. Multivariate analysis showed that shoulder pain was associated with age 10, 11, and 12 years, and that elbow pain was associated with age 10, 11, and 12 years, playing catcher, and >2 years of baseball experience. Training hours per week were not associated with either shoulder or elbow pain. CONCLUSION: In over 1000 baseball players aged 7 to 12 years, 15.9% reported episodes of shoulder pain, while 29.2% reported elbow pain in the throwing arm. The associated risk factors were different for each type of pain. Shoulder pain was associated with increased age while elbow pain was associated with increased age, increased years of baseball experience, and playing catcher. PMID- 26831220 TI - Corticotropin releasing factor excites neurons of posterior hypothalamic nucleus to produce tachycardia in rats. AB - Corticotropin releasing factor (CRF), a peptide hormone involved in the stress response, holds a key position in cardiovascular regulation. Here, we report that the central effect of CRF on cardiovascular activities is mediated by the posterior hypothalamic nucleus (PH), an important structure responsible for stress-induced cardiovascular changes. Our present results demonstrate that CRF directly excites PH neurons via two CRF receptors, CRFR1 and CRFR2, and consequently increases heart rate (HR) rather than the mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). Bilateral vagotomy does not influence the tachycardia response to microinjection of CRF into the PH, while beta adrenergic receptor antagonist propranolol almost totally abolishes the tachycardia. Furthermore, microinjecting CRF into the PH primarily increases neuronal activity of the rostral ventrolateral medulla (RVLM) and rostral ventromedial medulla (RVMM), but does not influence that of the dorsal motor nucleus of the vagus nerve (DMNV). These findings suggest that the PH is a critical target for central CRF system in regulation of cardiac activity and the PH-RVLM/RVMM-cardiac sympathetic nerve pathways, rather than PH-DMNV-vagus pathway, may contribute to the CRF-induced tachycardia. PMID- 26831222 TI - High Performance Transparent Transistor Memory Devices Using Nano-Floating Gate of Polymer/ZnO Nanocomposites. AB - Nano-floating gate memory devices (NFGM) using metal nanoparticles (NPs) covered with an insulating polymer have been considered as a promising electronic device for the next-generation nonvolatile organic memory applications NPs. However, the transparency of the device with metal NPs is restricted to 60~70% due to the light absorption in the visible region caused by the surface plasmon resonance effects of metal NPs. To address this issue, we demonstrate a novel NFGM using the blends of hole-trapping poly (9-(4-vinylphenyl) carbazole) (PVPK) and electron-trapping ZnO NPs as the charge storage element. The memory devices exhibited a remarkably programmable memory window up to 60 V during the program/erase operations, which was attributed to the trapping/detrapping of charge carriers in ZnO NPs/PVPK composite. Furthermore, the devices showed the long-term retention time (>10(5) s) and WRER test (>200 cycles), indicating excellent electrical reliability and stability. Additionally, the fabricated transistor memory devices exhibited a relatively high transparency of 90% at the wavelength of 500 nm based on the spray-coated PEDOT: PSS as electrode, suggesting high potential for transparent organic electronic memory devices. PMID- 26831223 TI - Phase transition in multimode nonlinear parity-time-symmetric waveguide couplers. AB - Parity-time-symmetric (-symmetric) optical waveguide couplers offer new possibilities for fast, ultracompact, configurable, all-optical signal processing. Here, we study nonlinear properties of finite-size multimode symmetric couplers and predict the nonlinear oscillatory dynamics that can be controlled by three parameters: input light intensity, gain and loss amplitude, and input beam profile. Moreover, we show that this dynamics is driven by a transition triggered by nonlinearity in these structures, and we demonstrate that with the increase of the number of dimers in the system, the transition threshold decreases and converges to the value corresponding to an infinite array. Finally, we present a variety of periodic intensity patterns that can be formed in these couplers depending on the initial excitation. PMID- 26831224 TI - Clinical Value of Tumor Markers for Determining Cause of Pleural Effusion. AB - BACKGROUND: It is often challenging to distinguish tuberculous pleural effusion (TPE) from malignant pleural effusion (MPE); thoracoscopy is among the techniques with the highest diagnostic ability in this regard. However, such invasive examinations cannot be performed on the elderly, or on those in poor physical condition. The aim of this study was to explore the differential diagnostic value of carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) associated antigen in patients with TPE and MPE. METHODS: Using electrochemiluminescence, we measured the concentration of tumor markers (TMs) in the pleural effusion and serum of patients with TPE (n = 35) and MPE (n = 95). We used receiver operating characteristic (ROC) curve analysis to evaluate the TMs and differentiate between TPE and MPE. RESULTS: The cut-off values for each TM in serum were: CA125, 151.55 U/ml; CA199, 9.88 U/ml; CEA, 3.50 ng/ml; NSE, 13.27 ng/ml; and SCC, 0.85 ng/ml. Those in pleural fluid were: CA125, 644.30 U/ml; CA199, 12.08 U/ml; CEA, 3.35 ng/ml; NSE, 9.71 ng/ml; and SCC, 1.35 ng/ml. The cut off values for the ratio of pleural fluid concentration to serum concentration (P/S ratio) of each TM were: CA125, 5.93; CA199, 0.80; CEA, 1.47; NSE, 0.76; and SCC, 0.90. The P/S ratio showed the highest specificity in the case of CEA (97.14%). ROC curve analysis revealed that, for all TMs, the area under the curve in pleural fluid (0.95) was significantly different from that in serum (0.85; P < 0.001). CONCLUSIONS: TMs in TPE differ significantly from those in MPE, especially when detected in pleural fluid. The combined detection of TMs can improve diagnostic sensitivity. PMID- 26831225 TI - A Mitochondrial DNA A8701G Mutation Associated with Maternally Inherited Hypertension and Dilated Cardiomyopathy in a Chinese Pedigree of a Consanguineous Marriage. AB - BACKGROUND: Cardiovascular diseases, including dilated cardiomyopathy (DCM) and hypertension, are the leading cause of death worldwide. The role of mitochondrial DNA (mtDNA) in the pathogenesis of these diseases has not been completely clarified. In this study, we evaluate whether A8701G mutation is associated with maternally inherited hypertension and DCM in a Chinese pedigree of a consanguineous marriage. METHODS: Fourteen subjects in a three-generation Han Chinese family with hypertension and DCM, in which consanguineous marriage was present in the parental generation, were interviewed. We divided all the family members into case (7 maternal members) and control group (7 nonmaternal members) for comparison. Clinical evaluations and sequence analysis of mtDNA were obtained from all participants. Frequency differences between maternal and nonmaternal members were tested to locate the disease-associated mutations. RESULTS: The majority of the family members presented with a maternal inheritance of hypertension and DCM. Sequence analysis of mtDNA in this pedigree identified eight mtDNA mutations. Among the mutations identified, there was only one significant mutation: A8701G (P = 0.005), which is a homoplasmic mitochondrial missense mutation in all the matrilineal relatives. There was no clear evidence for any synergistic effects between A8701G and other mutations. CONCLUSIONS: A8701G mutation may act as an inherited risk factor for the matrilineal transmission of hypertension and DCM in conjunction with genetic disorders caused by consanguineous marriage. PMID- 26831226 TI - Cytomegalovirus Pneumonia in Patients with Rheumatic Diseases After Immunosuppressive Therapy: A Single Center Study in China. AB - BACKGROUND: Rheumatic diseases involve multiple organs that are affected by immunological mechanisms. Treatment with corticosteroids and immunosuppressive agents may also increase the frequency of infection. Cytomegalovirus (CMV) is a widespread herpes virus and a well-recognized pathogen, which causes an opportunistic and potentially fatal infection in immunocompromised patients. This retrospective study aimed to investigate the clinical and laboratory characteristics of CMV pneumonia in patients with rheumatic diseases after immunosuppressive therapy in a single center in Shanghai, China. METHODS: Eight hundred and thirty-four patients with rheumatic diseases who had undergone CMV DNA viral load tests were included, and the medical records of 142 patients who were positive for CMV-DNA in plasma samples were evaluated. GraphPad Prism version 5.013 (San Diego, CA, USA) was used to conduct statistical analysis. The correlation between CMV-DNA viral loads and lymphocyte counts was assessed using the Spearman rank correlation coefficient test. Significance between qualitative data was analyzed using Pearson's Chi-squared test. The cut-off thresholds for CMV-DNA viral load and lymphocyte count were determined by receiver operating characteristic (ROC) curve analysis. RESULTS: One hundred and forty-two patients had positive CMV viral load tests. Of these 142 patients, 73 patients with CMV pneumonia were regarded as symptomatic, and the other 69 were asymptomatic. The symptomatic group received higher doses of prednisolone (PSL) and more frequently immunosuppressants than the asymptomatic group (P < 0.01). The symptomatic group had lower lymphocyte counts, especially CD4+ T-cells, than the asymptomatic group (P < 0.01). By ROC curve analysis, when CD4+ T-cell count was <0.39 * 109/L, patients with rheumatic diseases were at high risk for symptomatic CMV infection. The CMV-DNA load was significantly higher in the symptomatic patients than that in asymptomatic patients (P < 0.01; threshold viral loads: 1.75 * 104 copies/ml). Seven patients had a fatal outcome, and they had lower peripheral lymphocyte counts (P < 0.01), including CD4+ and CD8+ T-cells (P < 0.01). CONCLUSIONS: When CD4+ T-cell count is <0.39 * 109/L, patients are at high risk for pulmonary CMV infection. Patients are prone to be symptomatic with CMV-DNA load >1.75 * 104 copies/ml. Lymphopenia (especially CD4+ T-cells), presence of symptoms, and other infections, especially fungal infection, are significant risk factors for poor outcome, and a higher PSL dosage combined with immunosuppressants may predict CMV pneumonia. PMID- 26831227 TI - Efficacy and Safety of Bortezomib in Multiple Myeloma Patients with Hepatitis B: A Multicenter Retrospective Study. AB - BACKGROUND: The efficacy and safety evidence of bortezomib in multiple myeloma (MM) patients with hepatitis B is vacant. This study aimed to investigate the efficacy and safety of bortezomib in MM patients with hepatitis B in China. METHODS: From 2006 to 2011, 739 newly diagnosed MM patients were screened for serum hepatitis B virus (HBV) biomarkers. HBV-infected patients were followed for HBV reactivation by monitoring of serum alanine transaminase (ALT) and HBV DNA load. The pattern of HBV reactivation in relation to bortezomib was evaluated. Seven hundred thirty-nine MM patients were included in this study. RESULTS: The prevalence of MM patients infected with HBV was 3.4% (n = 25), of which 17 cases were treated with bortezomib. Bortezomib had no significant influence on liver function (ALT before and after treatment: 36.69 +/- 8.90 U/L vs. 11.31 +/- 2.74 U/L, P = 0.19) and HBV DNA of MM patients with HBV (detectable HBV DNA percentage: 5.9% vs. 11.8%, P = 0.12). CONCLUSIONS: Bortezomib can be used safely and effectively in MM patients with hepatitis B. HBV prophylaxis and surveillance are recommended during the MM treatment. PMID- 26831199 TI - Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function. AB - Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. PMID- 26831228 TI - Nonspecific Effect of Stress on Brain Gray Matter Volume in Drug-naive Female Patients with First Depressive Episode. AB - BACKGROUND: This study aimed to observe the differences in brain gray matter volume in drug-naive female patients after the first episode of major depression with and without stressful life events (SLEs) before the onset of depression. METHODS: Forty-three drug-naive female patients voluntarily participated in the present study after the first major depressive episode. The life event scale was used to evaluate the severity of the impact of SLEs during 6 months before the onset of the major depressive episode. High-field magnetic resonance imaging (MRI) scans were obtained, and the VBM and SPM8 software process were used to process and analyze the MRI. RESULTS: Compared to that in patients without SLEs, the volume of brain gray matter was lower in the bilateral temporal lobe, right occipital lobe, and right limbic lobe in the SLE group. However, the gray matter volume did not differ significantly between the two groups after the application of false discovery rate (FDR) correction. CONCLUSIONS: Although the results of the present study suggest the absence of significant differences in brain gray matter volume between female drug-naive patients after the first episode of major depression with and without SLEs after FDR correction, the study provides useful information for exploring the definitive role of stress in the onset of depression. PMID- 26831229 TI - Implementation of Constant Dose Rate and Constant Angular Spacing Intensity modulated Arc Therapy for Cervical Cancer by Using a Conventional Linear Accelerator. AB - BACKGROUND: Volumetric-modulated arc therapy (VMAT) can only be implemented on the new generation linacs such as the Varian Trilogy(r) and Elekta Synergy(r). This prevents most existing linacs from delivering VMAT. The purpose of this study was to investigate the feasibility of using a conventional linear accelerator delivering constant dose rate and constant angular spacing intensity modulated arc therapy (CDR-CAS-IMAT) for treating cervical cancer. METHODS: Twenty patients with cervical cancer previously treated with intensity-modulated radiation therapy (IMRT) using Varian Clinical 23EX were retreated using CDR-CAS IMAT. The planning target volume (PTV) was set as 50.4 Gy in 28 fractions. Plans were evaluated based on the ability to meet the dose volume histogram. The homogeneity index (HI), target volume conformity index (CI), the dose to organs at risk, radiation delivery time, and monitor units (MUs) were also compared. The paired t-test was used to analyze the two data sets. All statistical analyses were performed using SPSS 19.0 software. RESULTS: Compared to the IMRT group, the CDR-CAS-IMAT group showed better PTV CI (0.85 +/- 0.03 vs. 0.81 +/- 0.03, P = 0.001), clinical target volume CI (0.46 +/- 0.05 vs. 0.43 +/- 0.05, P = 0.001), HI (0.09 +/- 0.02 vs. 0.11 +/- 0.02, P = 0.005) and D95 (5196.33 +/- 28.24 cGy vs. 5162.63 +/- 31.12 cGy, P = 0.000), and cord D2 (3743.8 +/- 118.7 cGy vs. 3806.2 +/- 98.7 cGy, P = 0.017) and rectum V40 (41.9 +/- 6.1% vs. 44.2 +/- 4.8%, P = 0.026). Treatment time (422.7 +/- 46.7 s vs. 84.6 +/- 7.8 s, P = 0.000) and the total plan Mus (927.4 +/- 79.1 vs. 787.5 +/- 78.5, P = 0.000) decreased by a factor of 0.8 and 0.15, respectively. The IMRT group plans were superior to the CDR-CAS-IMAT group plans considering decreasing bladder V50 (17.4 +/- 4.5% vs. 16.6 +/- 4.2%, P = 0.049), bowel V30 (39.6 +/- 6.5% vs. 36.6 +/- 7.5%, P = 0.008), and low-dose irradiation volume; there were no significant differences in other statistical indexes. CONCLUSIONS: Patients with cervical cancer treated with CDR-CAS-IMAT using Varian Clinical 23EX can get equivalent or superior dose distribution compared to those treated with IMRT. CDR-CAS-IMAT has a less treatment time and MU, which can reduce the uncertainty factor and patient discomfort in treatment. PMID- 26831230 TI - Two Different Total Hip Arthroplasties for Hartofilakidis Type C1 Developmental Dysplasia of Hip in Adults. AB - BACKGROUND: Total hip arthroplasty (THA) in developmental dysplasia of the hip (DDH) is more complex than the normal hip, with large replacement risks and many complications. Although nonosteotomy THA is convenient to perform, femoral osteotomy shortening can avoid blood vessel and nerve traction injuries. This study aimed to compare osteotomy THA with nonosteotomy to determine reasonable options for operative management of DDH. METHODS: Data on 48 DDH patients who underwent THA were analyzed retrospectively. The patients were divided into two groups: Group A 29 cases (nonosteotomy), and group B 19 cases (osteotomy). Harris and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, limb length discrepancy (LLD), radiological data on the hip, and claudication were evaluated. Data were analyzed by using paired-sample Student's t-test, independent-sample Student's t-test, and Pearson's Chi-square test; the test level was alpha =0.05. RESULTS: Postoperative Harris (90.7 +/- 5.1) and WOMAC scores (88.0 +/- 10.6) were significantly improved compared with preoperative Harris (44.8 +/- 5.7) and WOMAC scores (42.0 +/- 5.3) in group A (P < 0.05). Postoperative Harris (90.4 +/- 2.8) and WOMAC scores (88.2 +/- 5.9) were significantly improved compared with preoperative Harris (44.4 +/- 4.2) and WOMAC scores (43.2 +/- 4.3) in group B (P < 0.05). One case of dislocation occurred in group A; after closed reduction, dislocation did not recur. In group A, 2 patients developed cutaneous branch injury of the femoral nerve, which spontaneously recovered without treatment. Postoperative LLD >2 cm was seen in one case in group A and five cases in group B. Postoperative claudication showed no significant difference between the two groups (P > 0.05). No patients developed infection; postoperative X-rays showed that the location of the prosthesis was satisfactory, and the surrounding bone was not dissolved. CONCLUSIONS: THA is effective and safe for DDH. For unilateral high dislocation DDH patients with limb lengthening <=4 cm and good tissue conditions, THA without femoral osteotomy may be considered. PMID- 26831231 TI - T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes. AB - BACKGROUND: Atopic dermatitis (AD) is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 (Th1/Th2) cytokine expression. Filaggrin (FLG) is the key protein to maintaining skin barrier function. Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes. However, the role of Th1/Th2 cytokines on FLG processing is not substantially documented. Our aim was to investigate the impact of Th1/Th2 cytokines on FLG processing. METHODS: HaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin (IL)-4, 13 or interferon-gamma (IFN-gamma). FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI) were measured by both real time quantitative polymerase chain reaction and Western blotting. Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry. RESULTS: IL-4/13 significantly reduced, while IFN-gamma significantly up-regulated FLG expression. IL-4/13 significantly increased, whereas IFN-gamma significantly decreased the expression of kallikreins 5 and 7, matriptase and channel-activating serine protease 1. On the contrary, IL-4/13 significantly decreased, while IFN-gamma increased the expression of LEKTI and caspase-14. Similar trends were observed in AD lesions. CONCLUSIONS: Our results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes. The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes. PMID- 26831232 TI - Efficacy and Safety of Tenofovir and Lamivudine in Combination with Efavirenz in Patients Co-infected with Human Immunodeficiency Virus and Hepatitis B Virus in China. AB - BACKGROUND: The prevalence of hepatitis B virus (HBV) infection is high among individuals infected with human immunodeficiency virus (HIV) in China. Both HIV and HBV can be treated with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC), so we evaluated the safety and efficacy of combination antiretroviral therapy (ART) that included TDF, 3TC, and efavirenz (EFV) among ART-naive individuals who were co-infected with HIV and HBV. METHODS: One hundred HIV/HBV co-infected ARV-naive individuals were started on the regimen of TDF, 3TC, and EFV, and the levels of plasma HBV DNA, HIV RNA, and biochemical evaluation related to the function of liver and kidney were analyzed. RESULTS: Concerning efficacy, this study found that by week 48, the vast majority co-infected participants receiving this ART regimen had undetectable HBV DNA levels (71%) and/or HIV RNA levels (90%). Concerning safety, this study found that the median estimated glomerular filtration rate of participants decreased from baseline (109 ml.min-1.1.73 m-2) to week 12 (104 ml.min-1.1.73 m-2) but was almost back to baseline at week 48 (111 ml.min-1.1.73 m-2). CONCLUSION: This combination ART regimen is safe and effective for patients with HIV/HBV co-infection. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01751555; https://clinicaltrials.gov/ct2/show/NCT01751555. PMID- 26831233 TI - High-resolution Sonographic Measurements of Lower Extremity Bursae in Chinese Healthy Young Men. AB - BACKGROUND: Lower extremity bursae are very vulnerable to injury during strenuous physical exercises. Understanding the imaging characteristics of normal bursae is essential for early diagnosis of morphological abnormalities. Therefore, we evaluated the normal range of lower extremity bursae in healthy young men using high-resolution ultrasound (HR-US) imaging. METHODS: Bursae in the lower extremities were examined by HR-US in 290 Chinese healthy young men with a median age of 18 years (range, 18-23 years). The bilateral suprapatellar bursa (SPB), deep infrapatellar bursa (DIPB), popliteal bursa (PB), and retrocalcaneal bursa (RCB) were imaged and measured for analysis. RESULTS: The HR-US identification rates of the SPB, DIPB, PB, and RCB were 89.0% (517/580), 55.0% (319/580), 29.4% (171/580), and 49.5% (287/580), respectively. With the assumption that the bursae were normal in 95% of the study participants, the length and width values at the maximal cross-section of the SPB, DIPB, PB, and RCB were <=18.00 and 6.09 mm, 8.10 and 2.11 mm, 7.67 and 3.93 mm, and 7.82 and 2.04 mm, respectively. CONCLUSIONS: Using HR-US imaging, we were able to analyze lower extremity bursae with high detection rates in healthy young men. The normal ranges of lower extremity bursa dimensions in healthy young men measured by HR-US in this study could be used as reference values for evaluation of bursa abnormalities in the lower extremity. PMID- 26831234 TI - Nerve Growth Factor Promotes Angiogenesis and Skeletal Muscle Fiber Remodeling in a Murine Model of Hindlimb Ischemia. AB - BACKGROUND: Therapeutic angiogenesis has been shown to promote blood vessel growth and improve tissue perfusion. Nerve growth factor (NGF) has been reported to play an important role in both physiological and pathological angiogenesis. This study aimed to investigate the effects of NGF on angiogenesis and skeletal muscle fiber remodeling in a murine model of hindlimb ischemia and study the relationship between NGF and vascular endothelial growth factor (VEGF) in angiogenesis. METHODS: Twenty-four mice were randomly allocated to normal control group (n = 6), blank control group (n = 6), VEGF gene transfection group (n = 6), and NGF gene transfection group (n = 6). The model of left hindlimb ischemia model was established by ligating the femoral artery. VEGF165plasmid (125 MUg) and NGF plasmid (125 MUg) was injected into the ischemic gastrocnemius of mice from VEGF group and NGF group, respectively. Left hindlimb function and ischemic damage were assessed with terminal points at 21th day postischemia induction. The gastrocnemius of four groups was tested by hematoxylin-eosin staining, proliferating cell nuclear antigen and CD34 immunohistochemistry staining, and myosin ATPase staining. NGF and VEGF protein expression was detected by enzyme linked immunosorbent assay. RESULTS: On the 21th day after surgery, the functional assessment score and skeletal muscle atrophy degree of VEGF group and NGF group were significantly lower than those of normal control group and blank control group. The endothelial cell proliferation index and the capillary density of VEGF group and NGF group were significantly increased compared with normal control group and blank control group (P < 0.05). The NGF and VEGF protein expression of NGF group showed a significant rise when compared with blank control group (P < 0.05). Similarly, the VEGF protein expression of VEGF group was significantly higher than that of blank control group (P < 0.05), but there was no significant difference of the NGF protein expression between VEGF group and blank control group (P > 0.05). The type I skeletal muscle fiber proportion in gastrocnemius of NGF group and VEGF group was significantly higher than that of blank control group (P < 0.05). CONCLUSIONS: NGF transfection can promote NGF and VEGF protein expression which not only can induce angiogenesis but also induce type I muscle fiber expression in ischemic limbs. PMID- 26831235 TI - Thalidomide-based Regimens for Elderly and/or Transplant Ineligible Patients with Multiple Myeloma: A Meta-analysis. AB - BACKGROUND: Thalidomide is an immunomodulatory and anti-angiogenic drug that has shown promise in patients with myeloma. Trials comparing efficacy of standard melphalan and prednisone (MP) therapy with MP plus thalidomide (MPT) in transplant-ineligible or elderly patients with multiple myeloma (MM) have provided conflicting evidence. This meta-analysis aimed to determine the efficacy and toxicity of thalidomide in previously untreated elderly patients with myeloma. METHODS: Medline, the Cochrane Controlled Trials register, conference proceedings of the American Society of Hematology (1995-2014), the American Society of Clinical Oncology (1995-2014), and CBM, VIP, and CNKI databases were searched for randomized control trials with the use of the medical subject headings "MM " and "thalidomide ". Trials were assessed by two reviewers for eligibility. Meta-analysis was conducted using a fixed effects model. Sensitivity analysis was performed to test the robustness of the findings. RESULTS: Overall, seven trials were identified, covering a total of 1821 subjects. The summary hazard ratio (thalidomide vs. control) was 0.82 (95% confidence interval [CI]: 0.72-0.94) for overall survival (OS), and 0.65 (95% CI: 0.58-0.73) for progression-free survival, in favor of thalidomide treated group. The risk ratio of complete response with induction thalidomide was 3.48 (95% CI: 2.24-5.41). A higher rate of III/IV adverse events were observed in MPT arm compared with the MP arm. However, analysis of sub-groups administering anticoagulation as venous thromboembolism prophylaxis suggested no difference in relative risk of thrombotic events between two arms (RR = 1.47, 95% CI: 0.43-5.07, P = 0.54). Further analysis of trials on the treatment effects of MPT versus MP on adverse events-related mortality showed no statistical difference between two arms (RR = 1.24, 95% CI: [0.95-1.63], P = 0.120). CONCLUSION: Thalidomide appears to improve the OS of elderly and/or transplant-ineligible patients with MM when it is added to standard MP therapy. PMID- 26831236 TI - Role of Circulating Fibrocytes in Cardiac Fibrosis. AB - OBJECTIVE: It is revealed that circulating fibrocytes are elevated in patients/animals with cardiac fibrosis, and this review aims to provide an introduction to circulating fibrocytes and their role in cardiac fibrosis. DATA SOURCES: This review is based on the data from 1994 to present obtained from PubMed. The search terms were "circulating fibrocytes " and "cardiac fibrosis ". STUDY SELECTION: Articles and critical reviews, which are related to circulating fibrocytes and cardiac fibrosis, were selected. RESULTS: Circulating fibrocytes, which are derived from hematopoietic stem cells, represent a subset of peripheral blood mononuclear cells exhibiting mixed morphological and molecular characteristics of hematopoietic and mesenchymal cells (CD34+/CD45+/collagen I+). They can produce extracellular matrix and many cytokines. It is shown that circulating fibrocytes participate in many fibrotic diseases, including cardiac fibrosis. Evidence accumulated in recent years shows that aging individuals and patients with hypertension, heart failure, coronary heart disease, and atrial fibrillation have more circulating fibrocytes in peripheral blood and/or heart tissue, and this elevation of circulating fibrocytes is correlated with the degree of fibrosis in the hearts. CONCLUSIONS: Circulating fibrocytes are effector cells in cardiac fibrosis. PMID- 26831237 TI - Evaluation of Three Small Molecular Drugs for Targeted Therapy to Treat Nonsmall Cell Lung Cancer. AB - OBJECTIVE: To guide the optimal selection among first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in clinical practice. This review attempted to provide a thorough comparison among three first-generation EGFR-TKIs, namely icotinib, erlotinib, and gefitinib, with regard to their molecular structure, pharmacokinetic parameters, clinical data, adverse reactions, and contraindications. DATA SOURCES: An electronic literature search of the PubMed database and Google Scholar for all the available articles regarding gefitinib, icotinib, and erlotinib in the English language from January 2005 to December 2014 was used. STUDY SELECTION: The search terms or keywords included but not limited to "lung cancer", "nonsmall cell lung cancer (NSCLC)", "epidemiology", "EGFR", "TKIs", and "optimal selection ". RESULTS: As suggested by this review, even though the three first-generation EGFR-TKIs share the quinazoline structure, erlotinib had the strongest apoptosis induction activity because of its use of a different side-chain. The pharmacokinetic parameters indicated that both erlotinib and icotinib are affected by food. The therapeutic window of erlotinib is narrow, and the recommended dosage is close to the maximum tolerable dosage. Icotinib enjoys a wider therapeutic window, and its concentration in the blood is within a safe dosage range even if it is administered with food. Based on multiple large-scale clinical trials, erlotinib is universally applied as the first-line treatment. In marked contrast, icotinib is available only in China as the second- or third-line therapeutic approach for treating advanced lung cancer. In addition, it exhibits a similar efficacy but better safety profile than gefitinib. CONCLUSIONS: Although there is a paucity of literature regarding whether icotinib is superior to erlotinib, its superior toxicity profile, noninferior efficacy, and lower cost indicate that it is a better alternative for Chinese patients living with advanced NSCLC. PMID- 26831239 TI - Rational Use of Computed Tomography for Individual Health Assessment in Asymptomatic Population: Chinese Experience. PMID- 26831240 TI - Research on China's Public Hospital Governance: From Perspective of Implementation Issues. PMID- 26831238 TI - Isoflavones and Prostate Cancer: A Review of Some Critical Issues. AB - OBJECTIVE: The purpose of this review is to discuss some critical issues of isoflavones protective against the development of prostate cancer (PCa). DATA SOURCES: Data cited in this review were obtained primarily from PubMed and Embase from 1975 to 2015. STUDY SELECTION: Articles were selected with the search terms "isoflavone", "Phytoestrogen", "soy", "genistin", and "PCa ". RESULTS: Isoflavones do not play an important role on prostate-specific antigen levels reduction in PCa patients or healthy men. The effect of isoflavones on sex hormone levels and PCa risk may be determined by equol converting bacteria in the intestine, specific polymorphic variation and concentrations of isoflavones. The intake of various types of phytoestrogens with lower concentrations in the daily diet may produce synergistic effects against PCa. Moreover, prostate tissue may concentrate isoflavones to potentially anti-carcinogenic levels. In addition, it is noteworthy that isoflavones may act as an agonist in PCa. CONCLUSIONS: Isoflavones play a protective role against the development of PCa. However, careful consideration should be given when isoflavones are used in the prevention and treatment of PCa. PMID- 26831241 TI - Ultrasound in Assessment of Supraspinatus Tendon Injury: Correlation with Arthroscopy. PMID- 26831242 TI - Clinicopathological Characteristics of Ten Patients with Atypical Glandular Hyperplasia Transformation of Adenomyosis. PMID- 26831243 TI - Computed Tomography Angiography in Diagnosis and Treatment of Splenic Artery Aneurysm. PMID- 26831244 TI - Meperidine-induced Seizure in an Adult Patient with Lung Lesions. PMID- 26831245 TI - Thymoma Complicated by Situs Inversus Totalis. PMID- 26831246 TI - Epidermoid Cyst Located in Facies Convexa Cerebri with Atypical Images. PMID- 26831247 TI - Lithium is Clearly Underutilized in Child Psychiatry. PMID- 26831248 TI - Clinical Misdiagnosis of Steatocystoma Simplex of Eyebrow in a Pediatric Patient. PMID- 26831249 TI - An Exact Procedure for the Evaluation of Reference-Scaled Average Bioequivalence. AB - Reference-scaled average bioequivalence (RSABE) has been recommended by Food and Drug Administration (FDA), and in its closely related form by European Medicines Agency (EMA), for the determination of bioequivalence (BE) of highly variable (HV) and narrow therapeutic index (NTI) drug products. FDA suggested that RSABE be evaluated by an approximating procedure. Development of an alternative, numerically exact approach was sought. A new algorithm, called Exact, was derived for the assessment of RSABE. It is based upon the observation that the statistical model of RSABE follows a noncentral t distribution. The parameters of the distribution were derived for crossover and parallel-group study designs. Simulated BE studies of HV and NTI drugs compared the power and consumer risk of the proposed Exact method with those recommended by FDA and EMA. The Exact method had generally slightly higher power than the FDA approach. The consumer risks of the Exact and FDA procedures were generally below the nominal error risk with both methods except for the partial replicate design under certain heteroscedastic conditions. The estimator of RSABE was biased; simulations demonstrated the appropriateness of Hedges' correction. The FDA approach had another, small but meaningful bias. The confidence intervals of RSABE, based on the derived exact, analytical formulas, are uniformly most powerful. Their computation requires in standard cases only a single-line program script. The algorithm assumes that the estimates of the within-subject variances of both formulations are available. With each algorithm, the consumer risk is higher than 5% when the partial replicate design is applied. PMID- 26831250 TI - Evaluation of the Microcentrifuge Dissolution Method as a Tool for Spray-Dried Dispersion. AB - Although using spray-dried dispersions (SDDs) to improve the bioavailability of poorly water-soluble compounds has become a common practice in supporting the early phases of clinical studies, their performance evaluation, whether in solid dosage forms or alone, still presents significant challenges. A microcentrifuge dissolution method has been reported to quickly assess the dissolution performance of SDDs. While the microcentrifuge dissolution method has been used in the SDD community, there is still a need to understand the mechanisms about the molecular species present in supernatant after centrifugation, the molecular nature of active pharmaceutical ingredients (APIs), as well as the impact of experimental conditions. In this paper, we aim to assess the effect of API and polymer properties on the dissolution behavior of SDDs along with centrifuging parameters, and for this, two poorly water-soluble compounds (indomethacin and ketoconazole) and two commonly used polymers in the pharmaceutical industry (PVP and HPMC-AS) were chosen to prepare SDDs. A typical microcentrifuge dissolution procedure as reported in the publication (Curatolo et al., Pharm Res 26:1419 1431, 2009) was followed. In addition, after separation of the supernatant from precipitation, some of the samples were filtered through filters of various sizes to investigate the particulate nature (particle size) of the supernatant. Furthermore, the centrifuge speed was varied to study sedimentation of API, SDD, or polymer particles. The results indicated that for the SDDs of four drug polymer pairs, microcentrifuge dissolution exhibited varied behaviors, depending on the polymer and the drug used. The SDDs of indomethacin with either PVP or HPMC-AS showed a reproducible dissolution with minimum variability even after filtration and subjecting to varied centrifugation speed, suggesting that the supernatant behaved solution-like. However, ketoconazole-PVP and ketoconazole HPMC-AS SDDs displayed a significant variation in concentration as the speed of centrifugation and the pore sizes of filters were altered, indicating that their supernatant was heterogeneous with the presence of particulates. In conclusion, microcentrifuge dissolution method was more suitable for indomethacin-PVP and indomethacin-HPMC-AS systems compared with ketoconazole-PVP and ketoconazole-HPMC AS. Therefore, the use of microcentrifuge dissolution method depends on both compounds and polymers selected, which should be examined case by case. PMID- 26831251 TI - Assessment and treatment of problem behavior maintained by mand compliance. AB - We modified functional analysis procedures to include a condition in which we reinforced problem behavior by complying with a child's mands. After identifying compliance with mands as a reinforcer, we evaluated the efficacy of a token system with a response-cost contingency and incorporated discriminative stimuli to signal when mands would be reinforced. The token system with response cost effectively reduced problem behavior. Similar procedures may be beneficial when continuous adult compliance is not possible, when adults want to control when they will comply with the child's mands, or to build a child's tolerance for adult-directed situations. PMID- 26831252 TI - Suitability of loci for multiple-locus variable-number of tandem-repeats analysis of Cryptosporidium parvum for inter-laboratory surveillance and outbreak investigations. AB - Cryptosporidium parvum is the major cause of livestock and zoonotically-acquired human cryptosporidiosis. The ability to track sources of contamination and routes of transmission by further differentiation of isolates would assist risk assessment and outbreak investigations. Multiple-locus variable-number of tandem repeats (VNTR) analysis provides a means for rapid characterization by fragment sizing and estimation of copy numbers, but structured, harmonized development has been lacking for Cryptosporidium spp. To investigate potential for application in C. parvum surveillance and outbreak investigations, we studied nine commonly used VNTR loci (MSA, MSD, MSF, MM5, MM18, MM19, MS9-Mallon, GP60 and TP14) for chromosome distribution, repeat unit length and heterogeneity, and flanking region proximity and conservation. To investigate performance in vitro, we compared these loci in 14 C. parvum samples by capillary electrophoresis in three laboratories. We found that many loci did not contain simple repeat units but were more complex, hindering calculations of repeat unit copy number for standardized reporting nomenclature. However, sequenced reference DNA enabled reproducible fragment sizing and inter-laboratory allele assignation based on size normalized to that of the sequenced fragments by both single round and nested polymerase chain reactions. Additional Cryptosporidium loci need to be identified and validated for robust inter-laboratory surveillance and outbreak investigations. PMID- 26831253 TI - Clinical Features of Long QT Syndrome in Children. PMID- 26831254 TI - Patent Ductus Arteriosus - A Complex Problem in Need of a Solid Conceptual Foundation. PMID- 26831255 TI - In vivo assessment of iron bioavailability from fortified pearl millet based weaning food. AB - BACKGROUND: Iron is an essential micronutrient required for normal growth and development of the body. Infants are more vulnerable to develop iron-deficiency anaemia due to inadequate iron supply in early stages. The objective of the study was in vivo assessment of iron bioavailability from pearl millet based weaning food fortified with iron and vitamin A, and to investigate the role of vitamin A in iron absorption in animal models. RESULTS: Results revealed that anaemic group showed significantly (P < 0.05) higher bioavailability than that of normal rat models. Animals fed vitamin A supplemented pearl-millet diet exhibited comparable results with a sub-group provided commercially available weaning diet in both normal and anaemic groups, but significantly (P < 0.05) higher values for studied biological indices than that of a sub-group provided iron fortified pearl-millet or synthetic diet. When the anaemic rats were provided iron + vitamin A fortified diet, iron bioavailability increased and liver iron stores returned to the normal levels after 30 days, indicating a promoter role of vitamin A in intestinal iron absorption. CONCLUSIONS: Overall, bioavailability of electrolytic iron could be improved by supplementation of vitamin A, and this mixture can be considered as a useful fortificant for pearl millet based complementary foods fortification designed to prevent iron deficiency. (c) 2016 Society of Chemical Industry. PMID- 26831256 TI - VARIAR Study: Assessment of short-term efficacy and safety of rituximab compared to an tumor necrosis factor alpha antagonists as second-line drug therapy in patients with rheumatoid arthritis refractory to a first tumor necrosis factor alpha antagonist. AB - OBJECTIVE: to compare the short-term efficacy and safety of rituximab (RTX) therapy versus anti-TNF in rheumatoid arthritis (RA) patients after discontinuation of a first anti-TNF agent. METHODS: prospective observational multicenter study in the clinical practice setting, involving patients with severe RA refractory to a first anti-TNF agent, who received either RTX or a second anti-TNF (2TNF), comparing the efficacy endpoints, EULAR response (Good/Moderate) and safety at 6 months. RESULTS: 103 patients enrolled, 82 completed 6-month follow-up, 73.7% women. Baseline data for RTX and 2TNF groups, respectively: TJC, 8.6 and 6.6; SJC, 8.8 and 7.5; DAS28 score, 5.45 (+/-1.28) and 5.18 (+/-1.21) (p=0.048), ESR, 41 and 38.7mmHg; and HAQ, 1.2 and 1.0. Improvement was observed in all parameters, with no significant differences (except for a more marked reduction in ESR with RTX). There were no serious adverse events. CONCLUSIONS: RTX use as second-line therapy after anti-TNF failure led to improvements in the efficacy and functional variables at 6 months, with no serious adverse events. These results were comparable to those observed in patients who used a second anti-TNF agent in the same clinical scenario. PMID- 26831257 TI - Neuroprotection by Vitamin C Against Ethanol-Induced Neuroinflammation Associated Neurodegeneration in the Developing Rat Brain. AB - Ethanol induces oxidative stress and its exposure during early developmental age causes neuronal cell death which leads to several neurological disorders. We previously reported that vitamin C can protect against ethanol-induced apoptotic cell death in the developing rat brain. Here, we extended our study to understand the therapeutic efficacy of vitamin C against ethanol-induced oxidative stress, neuroinflammation mediated neurodegeneration in postnatal day 7 (PND7) rat. A single episode of ethanol (5g/kg) subcutaneous administration to postnatal day 7 rat significantly induced the production of reactive oxygen species (ROS), and activated both microglia and astrocytes followed by the induction of different apoptotic markers. On the other hand, due to its free radical scavenging properties, vitamin C treatment significantly reduced the production of reactive oxygen species, suppressed both activated microglia and astrocytes and reversed other changes including elevated level of Bax/Bcl-2 ratio, cytochrome c and different caspases such as caspase-9 and caspase-3 induced by ethanol in developing rat brain. Moreover, vitamin C treatment also reduced ethanol-induced activation of Poly [ADP-Ribose] Polymerase 1(PARP-1) and neurodegeneration as evident from Flouro-Jade-B and Nissl stainined neuronal cell death in PND7 rat brain. These findings suggest that vitamin C mitigated ethanol-induced oxidative stress, neuroinflammation and apoptotic neuronal loss and may be beneficial against ethanol damaging effects in brain development. PMID- 26831258 TI - Inflammatory Mechanisms and Oxidative Stress as Key Factors Responsible for Progression of Neurodegeneration: Role of Brain Innate Immune System. AB - Chronic inflammation is characterized by longstanding microglial activation followed by sustained release of inflammatory mediators, which aid in enhanced nitrosative and oxidative stress. The sustained release of inflammatory mediators propels the inflammatory cycle by increased microglial activation, promoting their proliferation and thus stimulating enhanced release of inflammatory factors. Elevated levels of several cytokines and chronic neuroinflammation have been associated with many neurodegenerative disorders of central nervous system like age-related macular degeneration, Alzheimer disease, multiple sclerosis, Parkinson's disease, Huntington' disease, and tauopathies. This review highlights the basic mechanisms of neuroinflammation, the characteristics of neurodegenerative diseases, and the main immunologic responses in CNS neurodegenerative disorders. A comprehensive outline for the crucial role of microglia in neuroinflammation and neurodegeneration and the role of Toll-like receptor signalling in coexistence of inflammatory mechanisms and oxidative stress as major factors responsible for progression of neurodegeneration have also been presented. PMID- 26831259 TI - Implication of Green Tea as a Possible Therapeutic Approach for Parkinson Disease. AB - Green tea is a beverage consumed around the world that is believed to have substantial health benefits such as reducing the risk of cancer, cardiovascular diseases, diabetes and neurodegeneration. This beverage is prepared from the leaves (steamed and dried) of the Camellia sinesis plant and contains strong antioxidant and neuroprotective phenolic compounds from which the most important is (-)-Epigallocatechin-3-gallate. Parkinson's disease (PD) is the second more common neurodegenerative disorders, after Alzheimer's disease and is characterized by degeneration of dopaminergic neurons in the pars compact of the substantia nigra of the basal ganglia. It has been shown in pre-clinical and clinical studies that green tea may be able to prevent PD, but its optimal dose or a possible mechanism explaining its health benefit in PD has not been properly established. In this review, we discuss the potential role of green tea's phenolic compounds and their therapeutic effectin modulating key signaling pathways in the PD brain. PMID- 26831260 TI - Role of Microfluidics in Blood-Brain Barrier Permeability Cell Culture Modeling: Relevance to CNS Disorders. AB - In vitro modeling of the human blood-brain barrier (BBB) is critical for pre clinical evaluation and predicting the permeability of newly developed potentially neurotoxic and neurotrophic drugs. Here we summarize the specific structural and functional features of endothelial cells as a key component of the BBB and compare analysis of different cell culture models in reflecting these features. Particular attention is paid to cellular models of the BBB in microfluidic devices capable of circulating nutrient media to simulate the blood flow of the brain. In these conditions, it is possible to reproduce a number of factors affecting endothelial cells under physiological conditions, including shear stress. In comparison with static cell models, concentration gradients, which determine the velocity of transport of substances, reproduce more accurately conditions of nutrient medium flow, since they eliminate the accumulation of substances near the basal membrane of cells, not typical for the situation in vivo. Co-cultivation of different types of cells forming the BBB, in separate cell chambers connected by microchannels, allows to evaluate the mutual influences of cells under normal conditions and when exposed to the test substance. New experimental possibilities that can be achieved through modeling of BBB in microfluidic devices determine the feasibility of their use in the practice for pre-clinical studies of novel drugs against neurodegenerative diseases. PMID- 26831261 TI - Linkage of Stress with Neuromuscular Disorders. AB - Aging is associated with a progressive loss of muscle strength and mass, and a decline in neurophysiologic functions, which are characteristic features of neuromuscular disorders (NMDs). Understanding aging induced neuromuscular junction (NMJ) dysfunction is very crucial to understand the mechanism underlying NMDs. Morphological and physiological changes result in remodelling of the motor unit and a decline in the number of motor neuron muscle fibres. These alterations lead to excitation-contraction uncoupling and a loss of communication between the neuromuscular system, causing a decline in skeletal muscle strength and muscle mass. Understanding the molecular basis of NMJ dysfunction is essential in search for new treatment options. Besides structural and molecular studies, search for animal models to establish connection between brain and muscle is needed. Among various factors it has been observed that stress is one of the leading causes of NMDs. In the present review, we aim to explore various factors linking stress and NMDs neuromuscular disorders which gets aggravated by aging, with a special emphasis on mitochondrial connection. This in turn will help us gain new insights in the treatment of NMDs by aiding in improved symptoms, increased mobility and prolonged life. PMID- 26831262 TI - Recent Updates on the Dynamic Association Between Oxidative Stress and Neurodegenerative Disorders. AB - Free radicals are generated as byproduct of our body metabolism, and their adverse effect on normal functioning of our body is prevented by body's own antioxidant machinery. Any perturbation in the defense mechanism of antioxidants inside body, its abnormal production or its induction from environment to our body lead to serious threats and is responsible for the development of various neurodegenerative disorders (NDDs). Perturbed antioxidants result in sensory and functional impairments in neuronal cells, which in turn cause NDDs. Free radical attack on neuronal cells plays a catastrophic role in NDDs. Impaired metabolism and generation of excessive reactive oxygen species also lead to a range of NDDs. Free radical induced toxicity is responsible for DNA injury, protein degradation, damage to tissue inflammation and cell death. Besides various genetic and environmental factors, free radical induced oxidative stress is also a major cause of NDDs. Application of upstream and downstream antioxidant therapy to counter oxidative stress can be an effective option in alteration of any neuronal impairment besides free radical scavenging. In the present manuscript, we have presented a comprehensive update on the symptoms, causes and cures of NDDs in relation with their dynamic association with oxidative stress. PMID- 26831263 TI - The Co-Metabolism within the Gut-Brain Metabolic Interaction: Potential Targets for Drug Treatment and Design. AB - We know that within the complex mammalian gut is any number of metabolic biomes. The gut has been sometimes called the "second brain" within the "gut-brain axis". A more informative term would be the gut-brain metabolic interactome, which is coined here to underscore the relationship between the digestive system and cognitive function or dysfunction as the case may be. Co-metabolism between the host and the intestinal microbiota is essential for life's processes. How diet, lifestyle, antibiotics and other factors shape the gut microbiome constitutes a rapidly growing area of research. Conversely, the gut microbiome also affects mammalian systems. Metabolites of the gut-brain axis are potential targets for treatment and drug design since the interaction or biochemical interplay results in net metabolite production or end-products with either positive or negative effects on human health. This review explores the gut-brain metabolic interactome, with particular emphasis on drug design and treatment strategies and how commensal bacteria or their disruption lead to dysbiosis and the effect this has on neurochemistry. Increasing data indicate that the intestinal microbiome can affect neurobiology, from mental and even behavioral health to memory, depression, mood, anxiety, obesity, cravings and even the creation and maintenance of the blood brain barrier. PMID- 26831264 TI - Unsuspected Intrinsic Property of Melanin to Dissociate Water Can Be Used for the Treatment of CNS Diseases. AB - Retinal adhesion mechanisms in mammals are quite complex and multifactorial in nature. To date, these mechanisms are incompletely understood due to a variety of chemical, physical, and physiological forces impinging upon retinal tissue: retinal pigment epithelium, nearby tissues as sclera and vitreous, the subretinal space, and the highly complex interphotoreceptor matrix that fills subretinal space. The adhesion of the retina to the choroid, rather than anatomical, is a dynamic process, as the retina detaches a few minutes after life ceases. The adhesion mechanisms described in the literature, such as intraocular pressure and the oncotic pressure of the choroid that seems to push the retina towards the choroid, the delicate anatomical relationships between the rod and cone photoreceptors, the retinal pigment epithelium, the existence of a complex material called interphotoreceptor matrix, as well as other metabolic and structural factors, still cannot explain the remarkable features observed in the adhesion mechanisms between the photoreceptor layer and retinal pigment epithelium cells. The unexpected intrinsic property of melanin to absorb light energy and transform it into chemically based free energy can explain normal adhesion of the sensory retina to the pigment epithelium. In this article, we explore and highlight this explanation, which states that it is definitely able to provide a new treatment avenue against devastating neurodegenerative properties. PMID- 26831265 TI - Microglial dependent protective effects of neuroactive steroids. AB - Microglial cells are extremely important for homeostasis of the CNS. Upon brain damage, microglia become reactive in response to inflammatory stimuli and lead to the secretion of inflammatory cytokines. Because microglia have the ability of adjusting their steady state to an active phenotype that modulates the CNS environment, chronic activation of microglia has an important role in mediating neuroinflammatory brain diseases. Depending upon the nature and degree of the injury stimulus, microglial activity may alternate, either to acute and mild responses -sometimes beneficial- or chronic and severe that may result in neurodegeneration. In this context, proper and controlled activation of microglia should be considered as a potential neuroprotective strategy against neurodegeneration. More recently, the use of estrogenic compounds to regulate microgliosis has shown promising results, and is currently being investigated due to their potential pharmacologic ability in the regulation of inflammation. In this review, we highlight the role of microgliamediated damage and discuss the effect of neurosteroids in reducing the adverse impact of inflammation in the brain. PMID- 26831266 TI - A synopsis on the linkage between age-related dementias and vascular disorders. AB - The concept of age-related dementias and vascular disorders has now been recognized for over a century. In the present review, we have emphasized on the causes, consequences and the true bases for the treatment and prevention of these disorders. Systematic efforts have been put together to identify the aetiology in each case. Increased efforts have been targeted towards the concept and genetic factors responsible for vascular cognitive impairment and post-stroke dementia in relation with Alzheimer's disease, which is a consequence of age-related dementia, especially as they hold promise for early prevention and treatment. It has now been well accepted that vascular dementia is not a single disease but a group of conditions with different pathological correlations and pathophysiological mechanisms. The present review represents an amalgamation of several pathophysiological mechanisms producing a very heterogeneous clinical presentation for developing such consequences. We suggest current diagnostic categories and describe clinical parameters according to recently reported studies that document the demographic data in a standardized manner for age related dementia disorders. PMID- 26831267 TI - Novel Therapeutic Strategies for Dementia. AB - Dementia represents a major problem of health and disability, with a relevant economic impact on our society. Despite important advances in pathogenesis, diagnosis and treatment, its primary causes still remain elusive, accurate biomarkers are not well characterized, and the available pharmacological treatments are not cost-effective. Alzheimer disease (AD), the most prevalent form of dementia, is a polygenic/multifactorial/complex disorder in which hundreds of defective genes distributed across the human genome may contribute to its pathogenesis. Diverse environmental factors, cerebrovascular dysfunction, and epigenetic phenomena, together with structural and functional genomic dysfunctions lead to amyloid deposition, neurofibrillary tangle formation and premature neuronal death, the major neuropathological hallmarks of AD. For the past 20 years, over 1,000 different compounds have been studied as potential candidate drugs for the treatment of AD. About 50% of these substances are novel molecules obtained from natural sources. The candidate compounds can be classified according to their pharmacological properties and/or the AD-related pathogenic cascade to which they are addressed to halt disease progression. In addition to the Food and Drug Administration (FDA)-approved drugs since 1993 (tacrine, donepezil, rivastigmine, galantamine, memantine), most candidate strategies fall into 6 major categories: (i) novel cholinesterase inhibitors and neurotransmitter regulators, (ii) anti-amyloid beta (Abeta) treatments (amyloid beta protein precursor (APP) regulators, Abeta breakers, active and passive immunotherapy with vaccines and antibodies, beta - and gamma - secretase inhibitors or modulators), (iii) anti-tau treatments, (iv) pleiotropic products (most of them of natural origin), (v) epigenetic intervention, and (vi) combination therapies. The implementation of pharmacogenomic strategies will contribute to optimize drug development and therapeutics in AD and related disorders. PMID- 26831268 TI - [A point on a new year]. PMID- 26831269 TI - Development of intelligent systems based on Bayesian regularization network and neuro-fuzzy models for mass detection in mammograms: A comparative analysis. AB - Female breast cancer is the second most common cancer in the world. Several efforts in artificial intelligence have been made to help improving the diagnostic accuracy at earlier stages. However, the identification of breast abnormalities, like masses, on mammographic images is not a trivial task, especially for dense breasts. In this paper we describe our novel mass detection process that includes three successive steps of enhancement, characterization and classification. The proposed enhancement system is based mainly on the analysis of the breast texture. First of all, a filtering step with morphological operators and soft thresholding is achieved. Then, we remove from the filtered breast region, all the details that may interfere with the eventual masses, including pectoral muscle and galactophorous tree. The pixels belonging to this tree will be interpolated and replaced by the average of the neighborhood. In the characterization process, measurement of the Gaussian density in the wavelet domain allows the segmentation of the masses. Finally, a comparative classification mechanism based on the Bayesian regularization back-propagation networks and ANFIS techniques is proposed. The tests were conducted on the MIAS database. The results showed the robustness of the proposed enhancement method. PMID- 26831270 TI - Information theoretic multiscale truncated SVD for multilead electrocardiogram. AB - BACKGROUND AND OBJECTIVE: In this paper an information theory based multiscale singular value decomposition (SVD) is proposed for multilead electrocardiogram (ECG) signal processing. The shrinkage of singular values for different multivariate multiscale matrices at wavelet scales is based on information content. It aims to capture and preserve the information of clinically important local waves like P-waves, Q-waves, T-waves and QRS-complexes. METHODS: The information is derived through clinically relevant multivariate multiscale entropy in SVD domain modifying Shannon's entropy. This optimizes the approximate ranks for matrices to capture the clinical components of ECG signals appearing at different scales. A newly introduced multivariate clinical distortion (MCD) metric is computed and compared with existing subjective and objective signal distortion measures. The proposed method is tested with records from CSE multilead measurement library and PTB diagnostic ECG database for various pathological cases. RESULTS: It gives average percentage root mean square difference (PRD), average normalized root mean square error (NRMSE), average wavelet energy based diagnostic distortion measure (WEDD) values 5.8879%, 0.0059 and 1.0760% respectively for myocarditis pathology. The corresponding MCD value is 1.9429%. The highest average PRD and average WEDD values are 11.4053% and 5.5194% for cardiomyopathy with the corresponding MCD value 1.4003%. CONCLUSIONS: Based on WEDD values and mean opinion scores (MOS), the quality group of all processed signals fall under excellent category. PMID- 26831271 TI - Non-linear polynomial filters for edge enhancement of mammogram lesions. AB - BACKGROUND AND OBJECTIVES: Computer aided analysis of mammograms has been employed by radiologists as a vital tool to increase the precision in the diagnosis of breast cancer. The efficiency of such an analysis is dependent on the employed mammogram enhancement approach; as its major role is to yield a visually improved image for radiologists. METHODS: Non-linear Polynomial Filtering (NPF) framework has been explored previously as a robust approach for contrast improvement of mammographic images. This paper presents the extension of NPF framework for sharpening and edge enhancement of mammogram lesions. Proposed NPF serves to provide enhancement of edges and sharpness of the lesion region (region-of-interest) in mammograms, in a manner to minimize the dependencies on pre-selected thresholds. In the present work, Logarithmic Image Processing (LIP) model has been employed for the purpose of improvement in visualization of mammograms based on Human Visual System (HVS) characteristics. RESULTS: The proposed NPF filtering framework yields mammograms with significant improvement in contrast, edges as well as sharpness of the lesion region. The performance of the proposed approach has been validated using state-of-art objective evaluation measures (of mammogram enhancement) like Contrast Improvement Index (CII), Peak Signal-to-Noise Ratio (PSNR), Average Signal-to-Noise Ratio (ASNR) and Combined Enhancement Measure (CEM); as well as subjective evaluation by radiologists' opinions. CONCLUSIONS: The proposed NPF provides a robust solution to perform noise controlled contrast as well as edge enhancement using a single filtering model. This leads to a better visualization of the fine lesion details predictive of their severity. The applicability of single filtering methodology for carrying out denoising, contrast and edge enhancement improves the worth of the overall framework. PMID- 26831272 TI - Outbreak of parvovirus B19 infection among anesthesiology and surgical fellows. AB - A human parvovirus B19 outbreak was detected in personnel assigned to a surgical area (anesthesiology fellows and an otorhinolaryngology fellow) in a university hospital. The attack rate between susceptible members was higher than previous reports. Diagnosis was determined by polymerase chain reaction for human parvovirus B19 in serum of 1 subject and immunoglobulin M/immunoglobulin G antibody titer in the remaining subjects. Medical personnel were put on leave of absence until resolution of symptoms and laboratory confirmation of health. No cases of infection were detected in hospitalized patients or other health care workers on follow-up. PMID- 26831273 TI - Evaluation of the user seal check on gross leakage detection of 3 different designs of N95 filtering facepiece respirators. AB - BACKGROUND: The use of N95 respirators prevents spread of respiratory infectious agents, but leakage hampers its protection. Manufacturers recommend a user seal check to identify on-site gross leakage. However, no empirical evidence is provided. Therefore, this study aims to examine validity of a user seal check on gross leakage detection in commonly used types of N95 respirators. METHODS: A convenience sample of 638 nursing students was recruited. On the wearing of 3 different designs of N95 respirators, namely 3M-1860s, 3M-1862, and Kimberly Clark 46827, the standardized user seal check procedure was carried out to identify gross leakage. Repeated testing of leakage was followed by the use of a quantitative fit testing (QNFT) device in performing normal breathing and deep breathing exercises. Sensitivity, specificity, predictive values, and likelihood ratios were calculated accordingly. RESULTS: As indicated by QNFT, prevalence of actual gross leakage was 31.0%-39.2% with the 3M respirators and 65.4%-65.8% with the Kimberly-Clark respirator. Sensitivity and specificity of the user seal check for identifying actual gross leakage were approximately 27.7% and 75.5% for 3M 1860s, 22.1% and 80.5% for 3M-1862, and 26.9% and 80.2% for Kimberly-Clark 46827, respectively. Likelihood ratios were close to 1 (range, 0.89-1.51) for all types of respirators. CONCLUSIONS: The results did not support user seal checks in detecting any actual gross leakage in the donning of N95 respirators. However, such a check might alert health care workers that donning a tight-fitting respirator should be performed carefully. PMID- 26831274 TI - Antimicrobial-coated catheters and catheter-over-guidewire exchange in patients with severe catheter-related bloodstream infection: Old procedure, new indications? PMID- 26831276 TI - The use of passive visual stimuli to enhance compliance with handwashing in a perioperative setting. AB - BACKGROUND: To encourage handwashing, we analyzed the effect that a passive visual stimulus in the form of a picture of a set of eyes had on self-directed hand hygiene among health care staff. METHODS: This was a prospective, single blind study using a repeated measure design. Four dispensers of alcohol foam located in positions identified as #1, #2, #3, and #4 were used to deliver a single uniform volume of alcohol foam in an automated fashion. Pictures of eyes were placed on dispensers #1 and #3 but not dispensers #2 and #4 for 1 time period. The visual stimulus was rotated with each study time period. At the end of each study period, the volumes dispensed were examined to determine if the visual stimulus had a statistically significant influence on the volume dispensed. RESULTS: There were a total of 6 time periods. The average volume dispensed in stations with eyes was 279 cc versus that in the stations without eyes, which was 246 cc, and this was a statistically significant difference (P = .009). CONCLUSION: The correct visual stimuli may enhance compliance with hand hygiene in health care settings. PMID- 26831275 TI - Influence of high body mass index on mortality and infectious outcomes in patients who underwent open gastrointestinal surgery: A meta-analysis. AB - BACKGROUND: The influence of high body mass index (BMI) on mortality and infectious outcomes of patients following open gastrointestinal surgery was unclear. This meta-analysis aimed to resolve this controversy. METHODS: PubMed and EMBASE were searched by 2 researchers. High and normal BMIs were defined as >=25 and 18.5-24.99, respectively. Odds ratios (ORs) were calculated to compare the pooled effect sizes. The primary outcome was mortality. The secondary outcome was infectious outcomes, including surgical site, pulmonary infections, and urinary tract infections. RESULTS: Eleven eligible articles with 51,307 patients total were included. Compared with normal BMIs, high BMIs did not increase the risk of mortality (OR, 0.78; 95% confidence interval [CI], 0.58-1.06; P = .12). The secondary outcome indicated a significantly higher risk of infectious outcomes in high-BMI patients (OR, 1.34; 95% CI; 1.13-1.58; P = .0007). Among high-BMI patients, the risks of surgical site infections (OR, 1.75; 95% CI, 1.33 2.3; P < .0001) and pulmonary infections (OR, 1.2; 95% CI, 1.02-1.40; P = .03) increased significantly; urinary tract infections (OR, 1.10; 95% CI, 0.92-1.31; P = .30) did not show statistical difference. CONCLUSIONS: High BMI was associated with higher risks of infectious outcomes, including surgical site infections and pulmonary infections after open gastrointestinal surgery, but no association was observed between high BMI and urinary tract infections. PMID- 26831277 TI - Sustainability of a program for continuous reduction of catheter-associated urinary tract infection. AB - BACKGROUND: Urinary tract infections account for 8%-21% of health care-associated infections; of these, 80% are associated with the use of a urinary catheter. METHODS: A quasi-experimental study was conducted in 2 medical-surgical intensive care units (ICUs) with 48 beds and 3 step-down units (SDUs) with 95 beds in a private tertiary care hospital in Sao Paulo, Brazil. The study had 3 phases over a 9-year period to determine the sustainability of a program for continuous reduction of catheter-associated urinary tract infection (CAUTI). RESULTS: Over the 3 phases of the study, rates of CAUTI in the ICUs fell from 7.0 to 3.5 to 0.9 infections per 1,000 catheter days. In the SDUs, CAUTI rates decreased from 14.9 to 6.6 to 1.0 per 1,000 catheter days. Comparisons of CAUTI rates in the 3 study phases, both in the ICUs and SDUs, showed significant reductions both between the 3 periods and in all possible combinations of analysis phases (all P < .001). CONCLUSIONS: These results suggest that it is possible to reduce CAUTI rates to near zero and sustain these rates, but it requires a multidisciplinary team with different strategies that require continuous monitoring. PMID- 26831278 TI - Antimicrobial stewardship for carbapenem use at a Japanese tertiary care center: An interrupted time series analysis on the impact of infectious disease consultation, prospective audit, and feedback. AB - Given the concerns surrounding the overuse of carbapenem antibiotics in Japan, we evaluated the impact of infectious disease consultation and a prospective carbapenem audit at a tertiary care center in Tokyo, Japan. Overall, carbapenem use was safely and effectively reduced after implementation of these interventions. The leadership of the infectious diseases physicians also proved critically important to implementing effective stewardship. PMID- 26831279 TI - Control of endemic extensively drug-resistant Acinetobacter baumannii with a cohorting policy and cleaning procedures based on the 1 room, 1 wipe approach. AB - BACKGROUND: Our institution experienced an endemic situation with extensively drug-resistant (XDR) Acinetobacter baumannii in the intensive care units (ICUs). Here, we describe the long-term results of the implementation of a screening and cohorting policy and new cleaning techniques based on a procedure that we call the 1 room, 1 wipe approach. METHODS: We conducted a 4-year quasi-experimental study in the ICUs of an 800-bed teaching hospital. The main actions implemented were active surveillance of XDR A baumannii and cohorting of carriers and introducing new cleaning techniques intended to avoid sharing wipes between rooms. RESULTS: XDR A baumannii significantly decreased from 132 cases in 2011 to 8 cases in 2014 and from 10.78 cases per 1,000 patient days in 2011 to 0.69 cases per 1,000 patient days in 2014. Segmented regression analysis showed that after implementing the measures, the monthly rates presented a sustained negative slope, with a significant change of -0.623 (P = .002). CONCLUSIONS: The prompt identification and isolation of patients and adequate environmental cleaning are effective measures for reducing XDR A baumannii in ICUs. The 1 wipe, 1 room approach should be considered a standard measure for cleaning hospital facilities to avoid cross-transmission as a result of reusable cleaning wipes. PMID- 26831280 TI - Learning faces from variability. AB - Research on face learning has tended to use sets of images that vary systematically on dimensions such as pose and illumination. In contrast, we have proposed that exposure to naturally varying images of a person may be a critical part of the familiarization process. Here, we present two experiments investigating face learning with "ambient images"-relatively unconstrained photos taken from internet searches. Participants learned name and face associations for unfamiliar identities presented in high or low within-person variability-that is, images of the same person returned by internet search on their name (high variability) versus different images of the same person taken from the same event (low variability). In Experiment 1 we show more accurate performance on a speeded name verification task for identities learned in high than in low variability, when the test images are completely novel photos. In Experiment 2 we show more accurate performance on a face matching task for identities previously learned in high than in low variability. The results show that exposure to a large range of within-person variability leads to enhanced learning of new identities. PMID- 26831281 TI - Survey of Emergency Department Chemical Hazard Preparedness in Michigan, USA: A Seven Year Comparison. AB - OBJECTIVE: To compare the state of chemical hazard preparedness in emergency departments (EDs) in Michigan, USA between 2005 and 2012. METHODS: This was a longitudinal study involving a 30 question survey sent to ED directors at each hospital listed in the Michigan College of Emergency Physician (MCEP) Directory in 2005 and in 2012. The surveys contained questions relating to chemical, biological, radiological, nuclear, and explosive events with a focus on hazardous material capabilities. RESULTS: One hundred twelve of 139 EDs responded to the 2005 survey compared to 99/136 in 2012. Ten of 27 responses were statistically significant, all favoring an enhancement in disaster preparedness in 2012 when compared to 2005. Questions with improvement included: EDs with employees participating in the Michigan voluntary registry; EDs with decontamination rooms; MARK 1 and cyanide kits available; those planning to use dry decontamination, powered air purifiers, surgical masks, chemical gloves, and surgical gowns; and those wishing for better coordination with local and regional resources. Forty two percent of EDs in 2012 had greater than one-half of their staff trained in decontamination and 81% of respondents wished for more training opportunities in disaster preparedness. Eighty-four percent of respondents believed that they were more prepared in disaster preparedness in 2012 versus seven years prior. CONCLUSIONS: Emergency departments in Michigan have made significant advances in chemical hazard preparedness between 2005 and 2012 based on survey responses. Despite these improvements, staff training in decontamination and hazardous material events remains a weakness among EDs in the state of Michigan. PMID- 26831283 TI - Implementing the 2:1 student placement model in occupational therapy: Strategies for practice. AB - BACKGROUND/AIM: Health industry changes, including a growing demand for health professionals, have led to a greater need for clinical placements for occupational therapy and other health discipline students. As we develop programmes to accommodate larger numbers of student placements, there is a need to ensure that we understand the challenges and opportunities new models of supervision present and how any difficulties might be overcome. A large occupational therapy department in metropolitan Melbourne introduced a new 2:1 (two students to one supervisor) supervision model, moving away from the traditional 1:1 (one student to one supervisor) supervision model. This exploratory study examines supervisor experience in a trial of the new model. METHODS: The study adopted a social constructivist theoretical perspective and an exploratory qualitative design. Data were collected in two focus groups involving eight supervisors; one focus group was held prior to implementation of the 2:1 supervision model, and one post. A thematic analysis approach was used to identify, analyse and report patterns within the data. FINDINGS: The 2:1 placement model presented challenges particularly in relation to ensuring a quality placement and managing two students while acknowledging there were also opportunities for peer learning. Supervisors developed a number of strategies to minimise difficulties and maximise benefits, including taking an evidence-based approach, being prepared, mobilising organisational support and being positive but also pragmatic. CONCLUSIONS: The 2:1 student placement model is likely to be a model of choice in the future. There are challenges and opportunities associated with its use. This study identifies these as well as strategies for maximising opportunities and mitigating challenges. PMID- 26831282 TI - Huaier extract suppresses breast cancer via regulating tumor-associated macrophages. AB - Macrophages in tumor microenvironment are mostly M2-polarized - and have been reported to promote tumorigenesis, which are also defined as tumor-associated macrophages (TAMs). Here, we examined the regulatory effects of Huaier extract on TAMs using RAW264.7 murine macrophage cell line. Our data demonstrated that Huaier extract could inhibit the infiltration of macrophages into tumor microenvironment in a dose-dependent manner. By performing RT-PCR, immunofluorescence and phagocytosis assay, we were able to find that Huaier extract could regulate the polarization of macrophages, with decreased M2 polarization and increased phagocytosis of RAW264.7 cells. Moreover, we identified that Huaier extract could suppress macrophages-induced angiogenesis by using HUVEC migration assay, tube formation and chorioallantoic membrane assay. Additionally, western blotting showed decreased expression of MMP2, MMP9 and VEGF with the use of Huaier extract. Finally, we found that Huaier extract could inhibit M2-macrophages infiltration and angiogenesis through treating 4T1 tumor bearing mice with Huaier extract. Our study revealed a novel mechanism of the anti-tumor effect of Huaier extract which inhibited angiogenesis by targeting TAMs. These findings provided that Huaier was a promising drug for clinical treatment of breast cancer. PMID- 26831284 TI - A visco-poroelastic model of functional adaptation in bones reconstructed with bio-resorbable materials. AB - In this paper, the phenomena of resorption and growth of bone tissue and resorption of the biomaterial inside a bicomponent system are studied by means of a numerical method based on finite elements. The material behavior is described by a poro-viscoelastic model with infiltrated voids. The mechanical stimulus that drives these processes is a linear combination of density of strain energy and viscous dissipation. The external excitation is represented by a bending load slowly variable with sinusoidal law characterized by different frequencies. Investigated aspects are the influence of the load frequency, of type of the stimulus and of the effective porosity on the time evolution of the mass densities of considered system. PMID- 26831285 TI - Increase in illicit cigarette consumption in Brazil. PMID- 26831286 TI - 2016 ASCO Gastrointestinal Cancers Symposium. PMID- 26831287 TI - Framework for tackling paediatric chemotherapy drug shortages. PMID- 26831288 TI - Inadvisable breast and prostate cancer screenings in the USA. PMID- 26831289 TI - Prediction of chemotherapy benefit for colon cancers. PMID- 26831290 TI - US FDA's safety monitoring of drugs with expedited approval. PMID- 26831291 TI - Counting the cost of end-of-life cancer care. PMID- 26831292 TI - Evaluation and Detection of Dysplasia in IBD: the Role of Chromoendoscopy and Enhanced Imaging Techniques. AB - OPINION STATEMENT: Patients with ulcerative colitis (UC) and Crohn's disease (CD) colitis are at significantly higher risk for the development of colitis associated colorectal cancer (CAC), a risk associated with increased duration and extent of disease [1]. CAC in patients with ulcerative colitis and Crohn's colitis arises from dysplastic tissue in the background of mucosal inflammatory changes. Regular surveillance by colonoscopy is a recommended cancer prevention strategy endorsed by the US and European GI societies [2-4]. Until recently, random sampling of the mucosa throughout the colon has been the mainstay of this conventional surveillance. This requires multiple biopsies to be taken and processed, a practice which is time consuming, expensive, and has a low diagnostic yield. The growth pattern of dysplastic tissue is often multifocal and diffuse, and thus, its detection may not be optimal with the use of traditional white light colonoscopy. According to recent studies, most dysplastic lesions appear to be visible to careful endoscopic inspection [5-7]. Thus, the approach focusing on targeted biopsies of any mucosal abnormalities instead of only random biopsies has been advocated [8]. In addition, the detection and further delineation of any mucosal abnormalities are thought to be improved by the application of dyes that highlight more subtle abnormalities known as chromoendoscopy (CE) as well as a new generation endoscopic system with high definition white light endoscopy (HDWL). The application of CE in patients with long-term UC was deemed to be beneficial based upon the results of previous clinical trials comparing CE with standard definition white light endoscopy (SDWL) [9*, 10*]. However, there are limited data available comparing CE with the currently broadly used high-definition colonoscopies (HDWL) [11*, 12*, 13*]. High definition (HD) endoscopy uses a high-definition monitor and a high-resolution CCD (charge-coupled device) providing images of substantially higher resolution than standard video endoscopy. Thus, HDWL colonoscopy may be an alternative to CE in IBD surveillance without the need for the extra time and required experience with CE. Further longitudinal studies are necessary to determine the ultimate advantage of chromoendoscopy or lack of the advantages of chromoendoscopy over that of high-definition colonoscopy in detection of dysplasia. Once lesions are identified by HDWL and CE, they can be further evaluated with evolving technologies to perform in vivo microscopy. Small-field technologies such as confocal endomicroscopy (CLE) permit in vivo microscopic assessment of the colonic mucosa. This evolving technology can be utilized in combination with HDWL and CE in selected cases to further define the lesions and assess their histology, and thus, facilitate real-time in vivo diagnosis and decisions regarding resection of lesions. Further studies to determine the applicability of these newer enhanced technologies in evaluation of dysplasia in routine clinical practice are needed. PMID- 26831293 TI - Colonoscopy Surveillance and Management of Dysplasia in Inflammatory Bowel Disease. AB - OPINION STATEMENT: Patients with long-standing ulcerative colitis (UC) and extensive Crohn's disease (CD) colitis have a high risk of colorectal cancer (CRC) and are recommended to undergo surveillance with colonoscopy. Recent data highlights their increased risk of CRC compared to the general population despite colonoscopy surveillance. The proportion of IBD patients diagnosed with interval CRC within 6 to 36 months following a clearing colonoscopy was 15 %. Optimizing colonoscopy surveillance methods is important. Studies have demonstrated that the best endoscopic surveillance strategy to detect dysplasia is chromoendoscopy with surface application of dyes to enhance the mucosal visualization and that visible dysplasia should be endoscopically resected. In this chapter we will summarize the optimal surveillance and management techniques for colorectal dysplasia in IBD patients. PMID- 26831294 TI - Patient-Reported Outcomes in Eosinophilic Esophagitis and Achalasia. AB - OPINION STATEMENT: The activity of a particular esophageal disease, such as eosinophilic esophagitis (EoE) or achalasia, can be evaluated using clinician reported outcome (ClinRO) measures assessing various endoscopic, histologic, functional, and laboratory findings, and patient-reported outcome (PRO) measures. The patient-reported outcome (PRO) measures are those that are designed to be self-reported by patients. Commonly used PRO instruments include those that assess symptom severity, health-related quality of life, "general" quality of life, or health status. Regulatory authorities increasingly rely on PRO measures to support labeling claims for drug development. Validated PRO measures for various esophageal diseases are needed in order to unify and standardize the way disease activity is assessed, define clinically meaningful endpoints for use in interventional and observational studies, compare the efficacy/effectiveness of various therapies, and optimize therapeutic algorithms for management of these diseases. This article reviews commonly used PRO instruments designed to assess symptom severity and quality of life in adult patients with EoE and achalasia. PMID- 26831295 TI - Evidence-based approach to the treatment of hidradenitis suppurativa/acne inversa, based on the European guidelines for hidradenitis suppurativa. AB - Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease characterized by painful, recurrent nodules and abscesses that rupture and lead to sinus tracts and scarring. To date, an evidence-based therapeutic approach has not been the standard of care and this is likely due to the lack of evidence based treatment guidelines. The purpose of this study was to promote a holistic evidence-based approach which implemented Level of Evidence and Strength of Recommendation for the treatment of HS. Based upon the European Dermatology Forumguidelines for the management of HS, evidence-based approach was explored for the treatment of HS. The diagnosis of HS should be made by a dermatologist or other healthcare professional with expert knowledge in HS. All patients should be offered adjuvant therapy as needed (pain management, weight loss, tobacco cessation, treatment of super infections, and application of appropriate dressings). The treating physician should be familiar with disease severity scores, especially Hurley staging, physician global assessment and others. The routine use of patient'reported outcomesincluding DLQI, itch and pain assessment (Visual Analogue Scale) is strongly recommended. The need for surgical intervention should be assessed in all patients depending upon type and extent of scarring, and an evidence-based surgical approach should be implemented. Evidence based medical treatment of mild disease consists of topical Clindamycin 1 % solution/gel b.i.d. for 12 weeks or Tetracycline 500 p.o. b.i.d. for 4 months (LOE IIb, SOR B), for more widespread disease. If patient fails to exhibit response to treatment or for a PGA of moderate-to-severe disease, Clindamycin 300 p.o. b.i.d. with Rifampicin 600 p.o. o.d. for 10 weeks (LOE III, SOR C) should be considered. If patient is not improved, then Adalimumab 160 mg at week 0, 80 mg at week 2; then 40 mg subcutaneously weekly should be administered (LOE Ib, SOR A). If improvement occurs then therapy should be maintained as long as HS lesions are present. If the patient fails to exhibit response, then consideration of second or third line therapy is required. A growing body of evidence is being published to guide the treatment of HS. HS therapy should be based upon the evaluation of the inflammatory components as well as the scarring and should be directed by evidence-based guidelines. Treatment should include surgery as well as medical treatment. Future studies should include benefit risk ratio analysis and long term assessment of efficacy and safety, in order to facilitate long term evidence based treatment and rational pharmacotherapy. PMID- 26831296 TI - Endocrine disrupting chemicals (EDCs) and female cancer: Informing the patients. AB - Breast and uterine cancer are the most frequent female gender related neoplasms whose growth is mostly estrogen dependent. Therefore, any EDC exhibiting estrogenic effects may increase the risk of these two malignancies. This review focuses on the potential role of EDCs with estrogenic potential on the risk of breast and uterine neoplasms but also points to the possible role of the exposure to EDCs in the pathogenesis of ovarian and cervical cancer. It also underlines the necessity of informing the public about the presence of EDCs in common consumer products, their detrimental health effects and methods of reducing the exposure risk. PMID- 26831297 TI - A systematic database-derived approach to improve indexation of transpulmonary thermodilution-derived global end-diastolic volume. AB - Global end-diastolic volume (GEDV) has been indexed to body surface area (BSA). However, data validating this indexation of GEDV are scarce. Furthermore, it has been suggested to index GEDV to "predicted BSA" based on predicted body weight. Therefore, we aimed to identify biometric parameters independently associated with GEDV. We analyzed a database including 3812 TPTD measurements in 234 patients treated in the ICU of a German university hospital. GEDVI indexed to actual BSA was significantly lower than GEDVI indexed to predicted BSA (748 +/- 179 vs. 804 +/- 190 mL/m2; p < 0.001). GEDV was independently associated with older age, male sex, height, and actual body weight. In a regression model for the estimation of GEDV, age and height were the most important parameters: Each year in age and each cm in height increased GEDV by 9 and 15 mL, respectively. In addition to height and weight also age and sex should be considered for indexation of GEDV. PMID- 26831298 TI - Crossing Total Occlusions: Navigating Towards Recanalization. AB - Chronic total occlusions (CTOs) represent the "last frontier" of percutaneous interventions. The main technical challenges lies in crossing the guidewire into the distal true lumen, which is primarily due to three problems: device buckling during initial puncture, inadequate visualization, and the inability to actively navigate through the CTO. To improve the success rate and to identify future research pathways, this study systematically reviews the state-of-the-art of all existing and invented devices for crossing occlusions. The literature search was executed in the databases of Scopus and Espacenet using medical and instrument related keyword combinations. The search yielded over 840 patents and 69 articles. After scanning for relevancy, 45 patents and 16 articles were included. The identified crossing devices were subdivided based on the determinant for the crossing path through the occlusion, which is either the device (straight and angled crossing), the environment (least resistance, tissue selective, centerline, and subintimal crossing) or the user (directly steered and sensor enhanced crossing). It was found that each crossing path is characterized by specific advantages and disadvantages. For a future crossing device, a combination of crossing paths is suggested were the interventionist is able to exert high forces on the CTO (as seen in the device approach) and actively steer through the CTO (user: directly steered crossing) aided by intravascular imaging (user: sensor enhanced crossing) or an intrinsically safe device following the centerline or path of least resistance (environment: centerline crossing or least resistance crossing) to reach the distal true lumen. PMID- 26831299 TI - The insulinotropic effect of pulsatile compared with continuous intravenous delivery of GLP-1. AB - AIMS/HYPOTHESIS: In healthy individuals, both insulin and glucagon-like peptide 1 (GLP-1) are secreted in a pulsatile fashion. Insulin has greater glucose-lowering properties when administered in pulses compared with a constant i.v. infusion. The primary aim of this randomised double-dummy cross-over study was to compare the insulinotropic response to pulsatile and continuous i.v. infusions of equivalent doses of GLP-1. METHODS: Twelve healthy participants aged 18-35 years were randomised to three different treatments on separate days: a continuous infusion day (GLP-1 at 0.6 pmol kg(-1) min(-1) [1 ml/min] and a 1 ml placebo bolus every 6 min); a pulsatile infusion day (placebo at 1 ml/min and a 3.6 pmol/kg GLP-1 bolus every 6 min); and a placebo day (placebo at 1 ml/min and a 1 ml placebo bolus every 6 min). Between 45 and 120 min, a hyperglycaemic clamp was used to maintain blood glucose at 9 mmol/l. Venous blood glucose and plasma insulin concentrations were measured every 5 min from 0 to 45 min and every 1 min from 45 to 120 min; plasma glucagon was measured every 15 min. The order of treatment was randomised by the Pharmacy Department and both study investigators and participants were blinded to the treatment arm. The dextrose requirement and glucagon data were analysed using repeated measures ANOVA and insulin data were analysed with a linear mixed effects maximum likelihood model. RESULTS: Continuous and pulsatile infusions of GLP-1 increased the dextrose requirement by ~threefold (p < 0.001) and increased insulin secretion by ~ninefold (p < 0.001). There was no difference in the effect of both treatments. Although hyperglycaemia reduced plasma glucagon concentrations, there was no difference between the treatment days. CONCLUSIONS/INTERPRETATION: In healthy individuals, pulsatile and continuous administration of i.v. GLP-1 appears to have comparable insulinotropic effects. TRIAL REGISTRATION: ACTRN12612001040853 FUNDING: This study was supported by the National Health and Medical Research Council (NHMRC) of Australia. PMID- 26831300 TI - Associations of total amount and patterns of sedentary behaviour with type 2 diabetes and the metabolic syndrome: The Maastricht Study. AB - AIMS/HYPOTHESIS: The study investigated cross-sectional associations of total amount and patterns of sedentary behaviour with glucose metabolism status and the metabolic syndrome. METHODS: We included 2,497 participants (mean age 60.0 +/- 8.1 years, 52% men) from The Maastricht Study who were asked to wear an activPAL accelerometer 24 h/day for 8 consecutive days. We calculated the daily amount of sedentary time, daily number of sedentary breaks and prolonged sedentary bouts (>=30 min), and the average duration of the sedentary bouts. To determine glucose metabolism status, participants underwent an oral glucose tolerance test. Associations of sedentary behaviour variables with glucose metabolism status and the metabolic syndrome were examined using multinomial logistic regression analyses. RESULTS: Overall, 1,395 (55.9%) participants had normal glucose metabolism, 388 (15.5%) had impaired glucose metabolism and 714 (28.6%) had type 2 diabetes. The odds ratio per additional hour of sedentary time was 1.22 (95% CI 1.13, 1.32) for type 2 diabetes and 1.39 (1.27, 1.53) for the metabolic syndrome. No significant or only weak associations were seen for the number of sedentary breaks, number of prolonged sedentary bouts or average bout duration with either glucose metabolism status or the metabolic syndrome. CONCLUSIONS/INTERPRETATION: An extra hour of sedentary time was associated with a 22% increased odds for type 2 diabetes and a 39% increased odds for the metabolic syndrome. The pattern in which sedentary time was accumulated was weakly associated with the presence of the metabolic syndrome. These results suggest that sedentary behaviour may play a significant role in the development and prevention of type 2 diabetes, although longitudinal studies are needed to confirm our findings. PMID- 26831301 TI - Autophagy is a major regulator of beta cell insulin homeostasis. AB - AIMS/HYPOTHESIS: We studied the role of protein degradation pathways in the regulation of insulin production and secretion and hypothesised that autophagy regulates proinsulin degradation, thereby modulating beta cell function. METHODS: Proinsulin localisation in autophagosomes was demonstrated by confocal and electron microscopy. Autophagy was inhibited by knockdown of autophagy-related (ATG) proteins and using the H(+)-ATPase inhibitor bafilomycin-A1. Proinsulin and insulin content and secretion were assessed in static incubations by ELISA and RIA. RESULTS: Confocal and electron microscopy showed proinsulin localised in autophagosomes and lysosomes. Beta-Atg7 (-/-) mice had proinsulin-containing sequestosome 1 (p62 [also known as SQSTM1])(+) aggregates in beta cells, indicating proinsulin is regulated by autophagy in vivo. Short-term bafilomycin A1 treatment and ATG5/7 knockdown increased steady-state proinsulin and hormone precursor chromogranin A content. ATG5/7 knockdown also increased glucose- and non-fuel-stimulated insulin secretion. Finally, mutated forms of proinsulin that are irreparably misfolded and trapped in the endoplasmic reticulum are more resistant to degradation by autophagy. CONCLUSIONS/INTERPRETATION: In the beta cell, transport-competent secretory peptide precursors, including proinsulin, are regulated by autophagy, whereas efficient clearance of transport-incompetent mutated forms of proinsulin by alternative degradative pathways may be necessary to avoid beta cell proteotoxicity. Reduction of autophagic degradation of proinsulin increases its residency in the secretory pathway, followed by enhanced secretion in response to stimuli. PMID- 26831302 TI - GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial. AB - AIMS/HYPOTHESIS: Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has been demonstrated to successfully treat diabetes and promote weight loss. The mechanisms by which liraglutide confers weight loss remain to be fully clarified. Thus, we investigated whether GLP-1 receptors are expressed in human brains and whether liraglutide administration affects neural responses to food cues in diabetic individuals (primary outcome). METHODS: In 22 consecutively studied human brains, expression of GLP-1 receptors in the hypothalamus, medulla oblongata and parietal cortex was examined using immunohistochemistry. In a randomised (assigned by the pharmacy using a randomisation enrolment table), placebo-controlled, double-blind, crossover trial, 21 individuals with type 2 diabetes (18 included in analysis due to lack or poor quality of data) were treated with placebo and liraglutide for a total of 17 days each (0.6 mg for 7 days, 1.2 mg for 7 days, and 1.8 mg for 3 days). Participants were eligible if they had type 2 diabetes and were currently being treated with lifestyle changes or metformin. Participants, caregivers, people doing measurements and/or examinations, and people assessing the outcomes were blinded to the medication assignment. We studied metabolic changes as well as neurocognitive and neuroimaging (functional MRI) of responses to food cues at the clinical research centre of Beth Israel Deaconess Medical Center. RESULTS: Immunohistochemical analysis revealed the presence of GLP-1 receptors on neurons in the human hypothalamus, medulla and parietal cortex. Liraglutide decreased activation of the parietal cortex in response to highly desirable (vs less desirable) food images (p < 0.001; effect size: placebo 0.53 +/- 0.24, liraglutide -0.47 +/- 0.18). No significant adverse effects were noted. In a secondary analysis, we observed decreased activation in the insula and putamen, areas involved in the reward system. Furthermore, we showed that increased ratings of hunger and appetite correlated with increased brain activation in response to highly desirable food cues while on liraglutide, while ratings of nausea correlated with decreased brain activation. CONCLUSIONS/INTERPRETATION: For the first time, we demonstrate the presence of GLP-1 receptors in human brains. We also observe that liraglutide alters brain activity related to highly desirable food cues. Our data point to a central mechanism contributing to, or underlying, the effects of liraglutide on metabolism and weight loss. Future studies will be needed to confirm and extend these findings in larger samples of diabetic individuals and/or with the higher doses of liraglutide (3 mg) recently approved for obesity. TRIAL REGISTRATION: ClinicalTrials.gov NCT01562678 FUNDING : The study was funded by Novo Nordisk, NIH UL1 RR025758 and 5T32HD052961. PMID- 26831304 TI - The Relationship Between Suicide Ideation, Behavioral Health, and College Academic Performance. AB - The impact of suicidal ideation on college students' academic performance has yet to be examined, yet mental health is often linked with academic performance. Underclassmen and upperclassmen were compared on behavioral health outcomes related to academic success (N = 26,457). Ideation (b = -0.05, p < .05), increased mental health (b = -0.03, p < .01) or substance use severity (b = 0.02, p < .01) was associated with lower GPAs. Underclassmen's behavioral health severity was related to lower GPA. Students reported higher GPAs when participating in extracurricular activities during the past year. Ideation, beyond mental health, is an important when assessing academic performance. Increasing students' connections benefits students experiencing behavioral concerns but also aids in suicide prevention initiatives and improves academic outcomes. Creating integrated health care systems on campus where physical, mental health and academic support services is crucial to offer solutions for students with severe or co-morbid mental health histories. PMID- 26831303 TI - Metabolomics uncovers the role of adipose tissue PDXK in adipogenesis and systemic insulin sensitivity. AB - AIMS/HYPOTHESIS: We aimed to investigate the potential mechanisms involved in the compromised adipogenesis of visceral (VAT) vs subcutaneous adipose tissue (SAT) using comparative metabolomics. Based on the differentially identified metabolites, we focused on the relationship between the active form of vitamin B6 (pyridoxal 5-phosphate [PLP]), known to be generated through pyridoxal kinase (PDXK), and adipogenesis. METHODS: Non-targeted metabolomics analyses were performed in paired VAT and SAT (n = 14, discovery cohort). PDXK gene expression was evaluated in two validation cohorts of paired SAT and VAT samples in relation to obesity status and insulin sensitivity, and mechanistically after weight loss in vivo and in 3T3-L1 cells in vitro. RESULTS: Comparative metabolomics showed that PLP was significantly decreased in VAT vs SAT. Concordantly, PDXK mRNA levels were significantly decreased in VAT vs SAT, specifically in adipocytes. The decrease was specially marked in obese individuals. PDXK mRNA levels showed a strong association with adipogenic, lipid-droplet-related and lipogenic genes. At a functional level, systemic insulin sensitivity positively associated with PDXK expression, and surgically-induced weight loss (improving insulin sensitivity) led to increased SAT PDXK mRNA levels in parallel with adipogenic genes. In human pre-adipocytes, PDXK mRNA levels increased during adipocyte differentiation and after administration of peroxisome proliferator-activated receptor-gamma agonists, and decreased under inflammatory stimuli. Mechanistic studies in 3T3-L1 cells showed that PLP administration resulted in increased adipogenic mRNA markers during early adipogenesis, whereas the PLP antagonist 4-deoxypyridoxine exerted opposite effects. CONCLUSIONS/INTERPRETATION: Overall, these results support the notion that in situ production of PLP is required for physiological adipogenesis. PMID- 26831305 TI - Benefits and Harms of Screening Mammography by Comorbidity and Age: A Qualitative Synthesis of Observational Studies and Decision Analyses. AB - OBJECTIVE: We conducted a systematic review to assess the quality and limitations of published studies examining benefits and harms of screening mammography in relation to comorbidity and age. METHODS: We searched MEDLINE and EMBASE from January 1980 through June 2013 for studies that examined benefits or harms of screening mammography in women aged 65 years or older in relation to comorbidity. For each study, we extracted data regarding setting, design, quality, screening schedule, measure of comorbidity, and estimates of benefits and/or harms. We reviewed 1760 titles, identifying 7 articles that met the inclusion criteria: prospective cohort (two studies), retrospective cohort (two studies), and decision analyses (three studies). No randomized controlled trials were identified. RESULTS: At least one measure of life expectancy or reduction in the risk of breast cancer death as a marker of benefit was examined in four studies, whereas three studies addressed the harms of screening mammography, including false-positive results. Both cohort studies and decision analyses showed that screening benefits decreased with increasing age and comorbidity burden. CONCLUSIONS: The limited evidence currently available suggests that, apart from older women with severe comorbidity, women 65 and older may experience improvements in life expectancy from screening. Given the potential for harm, it is unclear whether the magnitude of the benefit is sufficient to warrant regular screening. Women, clinicians and policymakers should consider these factors in deciding whether continue screening. PMID- 26831307 TI - Empiricism as Change Agent. PMID- 26831306 TI - The Modified, Multi-patient Observed Simulated Handoff Experience (M-OSHE): Assessment and Feedback for Entering Residents on Handoff Performance. AB - BACKGROUND: Despite the identification of transfer of patient responsibility as a Core Entrustable Professional Activity for Entering Residency, rigorous methods to evaluate incoming residents' ability to give a verbal handoff of multiple patients are lacking. AIM: Our purpose was to implement a multi-patient, simulation-based curriculum to assess verbal handoff performance. SETTING: Graduate Medical Education (GME) orientation at an urban, academic medical center. PARTICIPANTS: Eighty-four incoming residents from four residency programs participated in the study. PROGRAM DESCRIPTION: The curriculum featured an online training module and a multi-patient observed simulated handoff experience (M OSHE). Participants verbally "handed off" three mock patients of varying acuity and were evaluated by a trained "receiver" using an expert-informed, five-item checklist. PROGRAM EVALUATION: Prior handoff experience in medical school was associated with higher checklist scores (23% none vs. 33% either third OR fourth year vs. 58% third AND fourth year, p = 0.021). Prior training was associated with prioritization of patients based on acuity (12% no training vs. 38% prior training, p = 0.014). All participants agreed that the M-OSHE realistically portrayed a clinical setting. CONCLUSIONS: The M-OSHE is a promising strategy for teaching and evaluating entering residents' ability to give verbal handoffs of multiple patients. Prior training and more handoff experience was associated with higher performance, which suggests that additional handoff training in medical school may be of benefit. PMID- 26831308 TI - Bernardo Houssay (1887-1971): Endocrine physiologist and Nobel laureate. PMID- 26831309 TI - Vaccination in the primary care setting: when is it safe to proceed? AB - Primary care practitioners play an important role in administering and advocating vaccinations against vaccine-preventable infectious diseases and ensuring herd immunity in our population. This is a follow-up article to an earlier one which dealt with the principles of vaccine scheduling and administration. This article describes several false contraindications to vaccination that a primary care practitioner may encounter, including pregnancy, current breastfeeding, history of febrile seizures, and having immunosuppressed or pregnant household contacts. We aimed to provide a guide for safe and timely vaccine administration in the primary care setting. PMID- 26831310 TI - Treatment of severe, disabling spasticity with continuous intrathecal baclofen therapy following acquired brain injury: the experience of a tertiary institution in Singapore. AB - INTRODUCTION: Intrathecal baclofen (ITB) therapy is a proven, effective treatment for disabling cortical spasticity. We describe the first local series of five patients with acquired brain injury (ABI) who received ITB and were followed up for 63.8 months. METHODS: A retrospective review of medical and rehabilitation records of patients who received ITB therapy was carried out. Data studied included baseline demographic and injury variables, implantation data, spasticity and function, ITB dosage over time and complications. RESULTS: From 2006 to 2010, a total of five patients received ITB therapy via implanted pumps about 39.4 months after ABI. Four out of five patients experienced significant reductions in their lower limb spasticity scores and improvements in global function and dependency. One patient had minor adverse events associated with baclofen-related sedation. The mean ITB dose at one year was 182.7 +/- 65.6 mcg/day. CONCLUSION: Our preliminary study showed encouraging long-term outcomes and safety for ITB therapy after ABI-related intractable spasticity. Individual ITB responses over time were variable, with gender differences. The outcomes experienced by our centre were comparable to those in the general ABI population, supporting the efficacy of ITB therapy for chronic disabling spasticity. PMID- 26831311 TI - A review of stab wound injuries at a tertiary trauma centre in Singapore: are self-inflicted ones less severe? AB - INTRODUCTION: In Singapore, as strict laws are a strong deterrent against armed violence, little is known about the epidemiology of penetrating stab wound injuries. Our study aimed to investigate the epidemiology of stab wound injuries at a major trauma centre in Singapore and determine if there was a difference in severity between self-inflicted stab wound (SI) injuries and those inflicted by others (IO). METHODS: We retrospectively reviewed all penetrating injuries at Tan Tock Seng Hospital, and identified and categorised all stab wound injuries as SI or IO. Basic demographic information, injury severity characteristics and outcome data were compared between these two groups. A review of all mortalities was performed, including recording the causes of death. RESULTS: Between 2005 and 2010, there were a total of 149 stab wound injuries, of which 24 (16.1%) were SI and 125 (83.9%) were IO injuries. Patients tended to be young (mean age 34.1 +/- 14.2 years). The mean Injury Severity Score was significantly different between the SI and IO groups (8.8 +/- 6.5 vs. 12.3 +/- 8.1; p = 0.03). In both groups, the majority underwent an operative procedure (83.3% vs. 85.6%) and had an average hospital stay of four days. CONCLUSION: The study confirms our hypothesis that SI injuries tend to be less severe than IO injuries and are more likely to occur at home rather than at a public area. This finding may be useful in the triage of patients with stab wound injuries. PMID- 26831312 TI - Underdiagnosis of delirium on admission and prediction of patients who will develop delirium during their inpatient stay: a pilot study. AB - INTRODUCTION: The study aimed to determine the prevalence and documentation of delirium among the elderly and if the Clock Drawing Test (CDT) can be used to predict which patients had delirium on admission and those who may develop delirium during their stay in acute medical wards. METHODS: A single researcher performed the Mini-Mental State Examination (MMSE) and CDT on admission and discharge of 57 elderly adults at the National University Hospital, Singapore. Delirium was defined as a >= 3-point improvement or >= 2-point decline in MMSE scores from admission to discharge, where a fall denotes development of delirium and a rise denotes resolution. The case notes of the same patients were reviewed for documentation of delirium. All inpatients from two acute medical wards were examined. One CDT score and a pair of MMSE scores were collected from each patient. RESULTS: A total of 57 patients (28 male, 29 female) were involved in the study. Their mean age was 76.0 +/- 8.7 years. The prevalence of delirium based on MMSE scores was 40.4%; 16 patients had delirium on admission while seven developed delirium during their inpatient stay. However, delirium was documented in the case notes of only 7 (30%) of the 23 patients. CDT score was better than baseline MMSE score at predicting a decline in MMSE score. CONCLUSION: The prevalence of delirium in the acute medical setting is high but underdiagnosed. The CDT may be a good screening tool to identify patients at risk of delirium during their inpatient stay. Baseline cognition screening should be performed in every elderly patient admitted to hospital. PMID- 26831313 TI - Differences in attitudes to end-of-life care among patients, relatives and healthcare professionals. AB - INTRODUCTION: This study explored and compared the differences in attitudes toward end-of-life care among patients, relatives and healthcare professionals, including doctors and nurses. METHODS: We performed a descriptive study on a cross-section of the population of a tertiary hospital in Singapore. Data was collected using a questionnaire survey involving 50 participants from each of the four groups of patients, relatives, doctors and nurses. RESULTS: Family members were the most commonly nominated surrogate decision-makers by the patient group (76%) and the majority of the relative group (74%) felt comfortable deciding on end-of-life care for their loved ones. However, the patient and relative groups differed significantly in their preferences on end-of-life care options, including cardiopulmonary resuscitation (CPR) (p = 0.001), intubation (p = 0.003), nasogastric tube feeding (p < 0.001) and the use of antibiotics (p = 0.023). Doctors, nurses and relatives demonstrated differences in preference between end-of-life care for themselves and for their loved ones, especially with regard to the use of nasogastric tube feeding. There was also a difference between patients and doctors in their decisions on CPR (p < 0.001) and intubation (p = 0.008). CONCLUSION: This study demonstrated the importance of early planning for end-of-life care. This must be initiated proactively by healthcare professionals to engage patients in a culturally sensitive manner to discuss their preferences, in order to facilitate open communication between the patient and family. PMID- 26831314 TI - Unusual morphology of scapulae: incidence and dimensions of ossified ligaments and supraspinous bony tunnels for clinical consideration. AB - INTRODUCTION: Knowledge of morphological variations of the suprascapular region is important in the management of entrapment neuropathy and interventional procedures. The objective of this study was to collect data on the morphological features and dimensions of ossified ligaments and unusual bony tunnels of scapulae from a North Indian population. METHODS: A total of 268 adult human scapulae of unknown gender were obtained from the bone bank of the Department of Anatomy, Dayanand Medical College and Hospital, Ludhiana, Punjab, India. The scapulae were evaluated for the incidence of ossified superior transverse scapular ligaments (STSLs), ossified inferior transverse scapular ligaments (ITSLs) and bony tunnels (i.e. the bony canal between the suprascapular notch and spinoglenoid notch), found along the course of the suprascapular nerve (SSN). The dimensions of these structures were measured and noted down. Ossified STSLs were classified based on their shape (i.e. fan- or band-shaped) and the dimensions of the ossified suprascapular openings (SSOs) were measured. RESULTS: Ossified STSLs were present in 26 (9.7%) scapulae. Among the 26 scapulae, 16 (61.5%) were fan shaped (mean area of SSO 16.6 mm(2)) and 10 (38.5%) were band-shaped (mean area of SSO 34.2 mm(2)). Bony tunnels were observed in 2 (0.75%) specimens, while an ossified ITSL was observed in 1 (0.37%) specimen. CONCLUSION: The data obtained in the present study augments the reference literature for SSN decompression and the existing anatomical databases, especially those on Indian populations. This data is useful to clinicians, radiologists and orthopaedic surgeons. PMID- 26831315 TI - Relationship between pulmonary function and degree of spinal deformity, location of apical vertebrae and age among adolescent idiopathic scoliosis patients. AB - INTRODUCTION: This retrospective review aimed to examine the relationship between preoperative pulmonary function and the Cobb angle, location of apical vertebrae and age in adolescent idiopathic scoliosis (AIS). To our knowledge, there have been no detailed analyses of preoperative pulmonary function in relation to these three factors in AIS. METHODS: A total of 38 patients with thoracic or thoracolumbar scoliosis were included. Curvature of spinal deformity was measured using the Cobb method. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were used to evaluate preoperative pulmonary function. Statistical methods were used to analyse the relationship between preoperative pulmonary function and the factors that may contribute to poor pulmonary function. RESULTS: The mean age of the patients was 16.68 +/- 6.04 years. An inverse relationship was found between the degree of the Cobb angle and FVC as well as FEV1; however, the relationships were not statistically significant (p = 0.057 and p = 0.072, respectively). There was also a trend towards a significant negative correlation between the thoracic curve and FVC (p = 0.014). Patients with larger thoracic curves had lower pulmonary function. A one-year increase in age significantly decreased FVC by 1.092 units (p = 0.044). No significant relationship between age and preoperative FEV1 was found. The median FVC was significantly higher in patients with affected apical vertebrae located at levels L1-L3 than at T6-T8 or T9-T12 (p = 0.006). CONCLUSION: Lung function impairment was seen in more severe spinal deformities, proximally-located curvature and older patients. PMID- 26831316 TI - Treatment of posterior cruciate ligament avulsion fractures of the tibia using a toothed plate and hollow lag screw. AB - INTRODUCTION: To investigate the feasibility and clinical efficacy of using a toothed plate and hollow lag screw in the surgical treatment of posterior cruciate ligament (PCL) avulsion fractures of the tibia. METHODS: A total of 21 patients were treated with open reduction and internal fixation using a toothed plate and hollow lag screw, through a posteromedial approach using an inverted L shaped incision. The patients were allowed appropriate functional exercises, including knee flexion and extension, after removal of the plaster at postoperative weeks 3-6. The follow-up period was between six months and two years. RESULTS: This was a retrospective study of patients with PCL avulsion fractures of the tibia caused by road traffic accidents (n = 9), sports-related injuries (n = 6), falls (n = 5) and machinery-related injuries (n = 1). 20 patients presented with fresh fractures and one with an old fracture. The patients (13 men, eight women) had a mean age of 41.5 (range 19-72) years. Anatomical reduction of the fracture and satisfactory fixation were achieved in all 21 patients. Bony union was achieved in all patients at 8-12 weeks after surgery. Six months after surgery, knee flexion was 121.9 degrees +/- 10.4 degrees and extension was 0 degrees . According to the Lysholm Knee Scoring Scale, 19 patients were rated as 'excellent' and two as 'good'. CONCLUSION: The use of a toothed plate and hollow lag screw could be a simple and reliable approach for PCL avulsion fractures of the tibia. Patients achieved good knee function after surgery. PMID- 26831317 TI - Clinics in diagnostic imaging (164). Morel-Lavallee lesion. AB - A 31-year-old male motorcyclist presented with prepatellar swelling of the left knee after a collision with a car. Magnetic resonance imaging of the knee showed no bony or ligamentous injury to the knee. Instead, a well-defined, thin-walled, T2-weighted hyperintense fluid collection with internal septations was identified in a prefascial location overlying the left patella and patellar tendon. The findings were in keeping with those of a Morel-Lavallee lesion, a closed internal degloving injury. Morel-Lavallee lesions are occasionally encountered after a blunt soft-tissue trauma. The presentation and imaging features are discussed. PMID- 26831318 TI - Striaelike epidermal necrosis. PMID- 26831319 TI - Adult intraventricular astroblastoma. PMID- 26831321 TI - Malignant anomalous right coronary artery associated with mid-cavitary hypertrophic obstructive cardiomyopathy. PMID- 26831320 TI - Elevated midline-parietal gamma band noise power in schizophrenia but not in bipolar patients. AB - Gamma oscillations are key in coordinating brain activity and seem to be altered in schizophrenia. In previous work, we studied the spatial distribution of a noise power measure (scalp-recorded electroencephalographic activity unlocked to stimuli) and found higher magnitudes in the gamma band related to symptoms and cognition in schizophrenia. In the current study, we sought to replicate those findings and to study its specificity for schizophrenia in a completely independent sample. A principal component analysis (PCA) was used to determine the factorial structure of gamma noise power acquired with an electroencephalographic recording during an odd-ball P300 paradigm in the 250- to 550-ms window in 70 patients with schizophrenia (16 patients with first episode), 45 bipolar patients and 65 healthy controls. Clinical and cognitive correlates of the resulting factors were also assessed. Three factors arose from the PCA. The first displayed a midline-parietal distribution (roughly corresponding to the default mode network), the second was centro-temporal and the third anterior frontal. Schizophrenia but not bipolar patients showed higher gamma noise power loadings in the first factor in comparison with controls. Scores for this factor were significantly and directly associated with positive and total symptoms in patients and inversely associated with global cognition in all participants. The results of this study replicate those of our previous publication and suggest an elevated midline-parietal gamma noise power specific to schizophrenia. The gamma noise power measure seems to be a useful tool for studying background oscillatory activity during performance of cognitive tasks. PMID- 26831322 TI - A highly selective, sensitive and reversible fluorescence chemosensor for Zn(2+) and its cell viability. AB - A new imine conjugate Schiff base ligand (H2L) was prepared and evaluated for its sensing properties. H2L detects Zn2+ selectively among the wide range of metal ions. The sensing behavior of H2L was identified by UV-vis, fluorescence and 1H NMR titration. H2L shows fluorescence switch ON with the Zn2+ ion among 18 other metal/heavy metal ions with a detection limit of 1.47 MUM. The binding of Zn2+ was confirmed by single crystal X-ray studies, which reveal the formation of binuclear complex (1). The packing diagram of H2L reveals the presence of rare linear C-H?C interactions (bond distance 2.79 A and bond angle 180 degrees ) which form 1D-polymeric chains. Furthermore, the cytotoxicity of H2L and 1 has been assessed against MCF-7 and A375 cell lines and both are found to have marginal toxicity. PMID- 26831324 TI - The relationship between tinnitus and vascular anomalies on temporal bone CT scan: a retrospective case control study. AB - INTRODUCTION: Tinnitus is a common symptom in which etiology is unclear in a group of patients. Some of anatomic or vascular variations diagnosed on temporal bone computed tomography (CT) has been known to cause tinnitus particulary pulsatile form. Therefore significance of these anatomic variations has not been validated in patients with nonpulsatile tinnitus. The aim of this study is to ascertain several anatomic variations previously attributed to pulsatile tinnitus in nonpulsatile tinnitus patients. And secondly to assess the relationship between the amount of sigmoid sinus bulging and mastoid emissary vein (MEV), enlargement of those was not evaluated before in tinnitus patients. METHODS: Retrospectively, temporal bone CT scans of 70 patients with an existing complaint of tinnitus with unexplained etiology were enrolled. As a control group, 70 patients were selected from paranasal sinus CT scans without any otological or clinical findings. RESULTS: The type of tinnitus was subjective and nonpulsatile in the overall group. The diameters of enlarged MEV on the left side were significantly higher in the tinnitus group. Carotid canal dehiscence and high riding jugular bulb were significantly higher in the tinnitus patients. Petrous bone pneumatization was significantly lower in the tinnitus patients than in the control group. CONCLUSIONS: In patients who complained of subjective nonpulsatile tinnitus with unknown etiology, some temporal bone vascular variations, including high riding jugular bulb, dehiscent carotid canal, left-sided MEV enlargement, and petrous bone pneumatization, seemed to have an association with tinnitus. Further studies comparing all these entities between pulsatile and nonpulsatile groups and healthy controls should be undertaken. PMID- 26831325 TI - A variant of the classical superficial brachioulnoradial artery: morphology and clinical significances. AB - We report a superficial brachioulnoradial artery (SBURA) presenting as a variant of the normal, originating from the proximal third of the right brachial artery of a 75-year-old female cadaver which bifurcated yielding a brachiointerosseous artery laterally and a SBURA medially, and the latter bifurcating 5 cm proximal to the elbow yielding a brachioradial artery laterally and the superficial brachioulnar artery medially, resulting in the formation of three instead of two brachial arteries as in the classical SBURA said to bifurcate at the elbow into the radial and ulnar arteries. Clinical implications of this variant are discussed. PMID- 26831326 TI - An arterial island pattern of the axillary and brachial arteries: a case report with clinical implications. AB - The variability of axillary and brachial arteries is often associated with neural anomalies in arrangement of the brachial plexus. The current report is focused on the coexistence of two brachial arteries of axillary origin with an atypical median nerve formatted by three (two lateral and a medial) roots in the right arm of a 68-year-old male cadaver. Medially, the brachial artery located in front of the median nerve was named superficial brachial artery and anastomosed with the brachial artery situated posterolateral to the median nerve, hence it is referred as the main brachial artery or brachial artery. Subsequently, the two arteries were recombined and the created arterial complex, like an island pattern, ended dividing into radial and ulnar arteries, at the level of the radial neck. To our knowledge, the combination of the above-mentioned arterial pattern to an abnormally formatted median nerve has not yet been cited. The current neurovascular abnormalities followed by an embryological explanation may have clinical implications. PMID- 26831327 TI - The posterior groove as a landmark for location of the palatovaginal canal in axial computed tomography. AB - PURPOSE: To investigate use of posterior groove of palatovaginal (PV) canal as an anatomic landmark in determining the location of PV canal in axial computed tomography (CT) images of pterygopalatine fossa (PPF). METHODS: A total of 20 skull specimens were examined in this analysis. Each skull was scanned by CT with and without a probe inserted through PV canal to measure the anatomic structures. CT images of 70 patients were used for comparing the rate of correct location of PV canal between the conventional method (using the vidian canal as a landmark) and the method of using the posterior groove as a landmark. Two skulls were dissected using endoscopy to further reveal the advantage of the posterior groove as a landmark. RESULTS: In all 20 skull specimens, the groove showed the morphology of a narrow groove and elliptical fossa in 24 and 16 sides, respectively. In CT images, the angle from PV canal and the posterior groove to the hard palate was 53.14 degrees +/- 5.48 degrees and 20.93 degrees +/- 6.28 degrees , respectively, which was significantly different (P <= 0.05). The rate of correct location of PV canal was statistically significantly higher with the method of posterior groove as a landmark than the conventional method (70.7 vs 49.3 %, P < 0.05). The endoscopic anatomy of the posterior groove and its use in locating the PV canal were described. CONCLUSION: The posterior groove can be used as an anatomic landmark in correctly locating PV canal in the axial CT image of the PPF. PMID- 26831328 TI - Oritavancin: A New Lipoglycopeptide Antibiotic in the Treatment of Gram-Positive Infections. AB - Resistance among Gram-positive organisms has been steadily increasing over the last several years; however, the development of new antibiotics to treat infections caused from these organisms has fallen short of the emergent need. Specifically, resistance among Staphylococcus aureus and Enterococcus spp. to essential antibiotics is considered a major problem. Oritavancin is a semisynthetic lipoglycopeptide antibiotic that was recently approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI). While structurally related to vancomycin, oritavancin also possesses unique mechanisms of action that greatly enhance its antimicrobial potency against multi-drug resistant pathogens including both VanA- and VanB-mediated vancomycin-resistant enterococci. Owing to the addition of the highly hydrophobic tail group, oritavancin possesses a prolonged half-life ranging from 200-300 h. Although oritavancin is only currently Food and Drug Administration approved for ABSSSI, this agent may eventually play a role in additional indications where new innovative therapy is needed including bacteremia and deep-seeded, Gram-positive infections such as infective endocarditis or osteomyelitis. This review will focus on oritavancin's spectrum of activity, mechanisms of action and resistance, pharmacokinetic and pharmacodynamic properties, and the completed and ongoing clinical studies evaluating its use. PMID- 26831329 TI - Knowledge structure and theme trends analysis on general practitioner research: A Co-word perspective. AB - BACKGROUND: General practitioners (GPs) are the most important providers of primary health care, as proven by related research published several decades ago. However, the knowledge structure and theme trends of such research remain unclear. Accordingly, this study aimed to provide an overview of the development of research on GPs over the period of 1999 to 2014. METHODS: Studies on GPs conducted from 1999 to 2014 were retrieved from PubMed. In this work, co-word, social network analysis, and theme trends analyses were conducted to reveal the knowledge structures and thematic evolution of research on GPs. RESULTS: The number of conducted studies on GPs increased. However, growth speed slowed down during the past 16 years. A total of 27 high-frequency keywords were identified in 1999 to 2003, and more new and specific high-frequency keywords emerged in the subsequent periods. The dynamic of this field was first divergent and then considered convergent. Specifically, network centralization is 19.77%, 19.09%, and 13.04% in 1999 to 2003, 2004 to 2008 and 2009 to 2014, respectively. The major topics of research on GPs completed from 1999 to 2014 were "physician/family,""attitude of health personnel," and "primary health care," and "general practitioner" communities, and so on. CONCLUSION: The research themes on GPs are relatively stable at the beginning of the 21(st) century. However, the thematic evolution and research topics of research on GPs are changing dynamically in recent years. Themes related to the roles and competencies of GPs, and the relations between general practitioner and patients/others have become research foci on GPs. In addition, more substantial research especially on comprehensive approaches and holistic modeling, which have been defined in the European Definition of General Practice/Family Medicine, are expected to be accomplished. PMID- 26831330 TI - Patient representatives' views on patient information in clinical cancer trials. AB - BACKGROUND: Patient enrolment into clinical trials is based on oral information and informed consent, which includes an information sheet and a consent certificate. The written information should be complete, but at the same time risks being so complex that it may be questioned if a fully informed consent is possible to provide. We explored patient representatives' views and perceptions on the written trial information used in clinical cancer trials. METHODS: Written patient information leaflets used in four clinical trials for colorectal cancer were used for the study. The trials included phase I-III trials, randomized and non-randomized trials that evaluated chemotherapy/targeted therapy in the neoadjuvant, adjuvant and palliative settings. Data were collected through focus groups and were analysed using inductive content analysis. RESULTS: Two major themes emerged: emotional responses and cognitive responses. Subthemes related to the former included individual preferences and perceptions of effect, while subthemes related to the latter were comprehensibility and layout. Based on these observations the patient representatives provided suggestions for improvement, which largely included development of future simplified and more attractive informed consent forms. CONCLUSIONS: The emotional and cognitive responses to written patient information reported by patient representatives provides a basis for revised formats in future trials and add to the body of information that support use of plain language, structured text and illustrations to improve the informed consent process and thereby patient enrolment into clinical trials. PMID- 26831331 TI - Prevalence and factors associated with intestinal parasitic infections among food handlers of Southern Ethiopia: cross sectional study. AB - BACKGROUND: Globally about one third of the total population is estimated to be infected with intestinal parasites, of which, the majority are people living in tropical and sub-tropical parts of the world. Cases of intestinal parasitosis are also highly abundant in Ethiopia and hence the aim of present study was to assess prevalence and predictors of intestinal parasitic infections among food handlers working in Arba Minch University students' cafeteria, South Ethiopia. METHOD: A cross sectional study was conducted among food handlers working in Arba Minch University from April to June, 2015. A pretested structured questionnaire was used for collecting data about socio-demographic characteristics and possible risk factors. Stool specimens were collected and examined microscopically for the presence of eggs, cysts and trophozoites of intestinal parasites. Data entry and analysis were done using SPSS version 20 software. RESULTS: A total of 376 food handlers were enrolled in the study of which thirty one of them were not willing to participate for a stool examination. The majority of study participants were females 273 (72.6 %). About 123 (36 %) of food handlers were found to be positive for different intestinal parasites with the most abundant parasite of Entamoeba histolytica/dispar 48 (14 %) followed by Ascaris lumbricoides 32 (9.27 %). Finger nail status (AOR: 2.2, 95 % CI: 1.29-3.72), hand washing practice after toilet (AOR: 1.71, 95 % CI: 1.06-2.77), hand washing practice before food handling (AOR: 1.69, 95 % CI: 1.04-2.75), preparing food when suffering from diseases (AOR: 3.08, 95 % CI: 1.17-8.13), and using common knife for cutting raw flesh food and other food (AOR: 1.72, 95 % CI: 1.01-2.92) were independent predictors of intestinal parasitic infection among the food handlers. CONCLUSION: This study revealed a high prevalence of intestinal parasites among food handlers. Since most of the intestinal parasites are transmitted by the feco-oral route, food handlers could be an important source of infection to the students and general population. Therefore, constant epidemiological surveillance through biannual routine parasitological tests and treatment of the infected cases along with the improvement of personal hygiene and environmental sanitation are recommended to control the parasitic infection in food handlers. PMID- 26831333 TI - Antioxidant activity of linalool in patients with carpal tunnel syndrome. AB - BACKGROUND: Carpal tunnel syndrome (CTS) is a common peripheral neuropathy and ischemic-reperfusion injury. Oxidative stress is considered a major cause of CTS. Linalool, a component of essential oils, has antioxidant activity. This study was designed to determine the effects of linalool inhalation on oxidative stress in patients with CTS. METHODS: This double-blind, placebo-controlled study assessed the effects of linalool inhalation on oxidative stress in patients with CTS. Thirty-seven subjects, with and without CTS, were randomized to inhalation of 1% linalool or carrier oil. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, systolic blood pressure (sBP), diastolic blood pressure (dBP) and pulse rate were analyzed. RESULTS: DPPH inhibition was significantly higher in both experimental groups than in their respective controls. Moreover inhalation of linalool reduced sBP, dBP and pulse rate in the CTS group, and pulse rate in the non-CTS group. However, there were no significant differences among the study groups in nitrite levels, sBP, dBP and pulse rate. CONCLUSIONS: Inhalation of linalool increases antioxidative activity and reduces blood pressure and pulse rate in patients with CTS. PMID- 26831332 TI - The impact of nurse-driven targeted HIV screening in 8 emergency departments: study protocol for the DICI-VIH cluster-randomized two-period crossover trial. AB - BACKGROUND: In 2010, to reduce late HIV diagnosis, the French national health agency endorsed non-targeted HIV screening in health care settings. Despite these recommendations, non-targeted screening has not been implemented and only physician-directed diagnostic testing is currently performed. A survey conducted in 2010 in 29 French Emergency Departments (EDs) showed that non-targeted nurse driven screening was feasible though only a few new HIV diagnoses were identified, predominantly among high-risk groups. A strategy targeting high-risk groups combined with current practice could be shown to be feasible, more efficient and cost-effective than current practice alone. METHODS/DESIGN: DICI VIH (acronym for nurse-driven targeted HIV screening) is a multicentre, cluster randomized, two-period crossover trial. The primary objective is to compare the effectiveness of 2 strategies for diagnosing HIV among adult patients visiting EDs: nurse-driven targeted HIV screening combined with current practice (physician-directed diagnostic testing) versus current practice alone. Main secondary objectives are to compare access to specialist consultation and how early HIV diagnosis occurs in the course of the disease between the 2 groups, and to evaluate the implementation, acceptability and cost-effectiveness of nurse driven targeted screening. The 2 strategies take place during 2 randomly assigned periods in 8 EDs of metropolitan Paris, where 42 % of France's new HIV patients are diagnosed every year. All patients aged 18 to 64, not presenting secondary to HIV exposure are included. During the intervention period, patients are invited to fill a 7-item questionnaire (country of birth, sexual partners and injection drug use) in order to select individuals who are offered a rapid test. If the rapid test is reactive, a follow-up visit with an infectious disease specialist is scheduled within 72 h. Assuming an 80 % statistical power and a 5 % type 1 error, with 1.04 and 3.38 new diagnoses per 10,000 patients in the control and targeted groups respectively, a sample size of 140,000 patients was estimated corresponding to 8,750 patients per ED and per period. Inclusions started in June 2014. Results are expected by mid-2016. DISCUSSION: The DICI-VIH study is the first large randomized controlled trial designed to assess nurse-driven targeted HIV screening. This study can provide valuable information on HIV screening in health care settings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02127424 (29 April 2014). PMID- 26831334 TI - Top ten research priorities for brain and spine cavernous malformations. PMID- 26831335 TI - Greater improvement in LRRK2 G2019S patients undergoing Subthalamic Nucleus Deep Brain Stimulation compared to non-mutation carriers. AB - BACKGROUND: Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) of parkinson's disease (PD) patients has demonstrated to improve motor performance and to reduce dopa-induced dyskinesia. An association between the occurrence of dyskinesias and LRRK2 (leucine-rich repeat kinase 2) G2019S gene mutations has recently been suggested. The aim of this study is to discover the impact of the G2019S mutation (with high incidence in the authors' native Algeria) on the symptom response of PD in patients who underwent STN-DBS. METHODS: We carried out a comparative statistical study for the clinical evaluation and neuropsychological assessment of 27 Algerian PD STN-DBS patients, both G2019S mutation carriers (MC) and non-carriers (NC). A multiple correspondence analysis (MCA) was then conducted to compare the results with those from groups of individuals with similar modalities. RESULTS: The MCA revealed that MC and NC PD patients showed two different patterns of clinical evaluations. The group of idiopathic patients showed some differences compared to the clinical evaluations, depending on gender. No association was found between the G2019S mutation and the Mini Mental State Examination scores (MMSE), and MC patients appeared more susceptible to dyskinesia than NC patients. In NC patients, we found two cases with Parkin mutations who had a different "honeymoon" period and different initial symptoms. The results showed considerable improvement of motor unified parkinson's disease rating scale III (UPDRS-III) in a situation of stimulation without medication in the MC patients with a percentage of improvement (51.1 %) over the required 30 % compared to the NC patients (25.5 %). The same result was observed for the Schwab and England's activities of daily living scale (S and E scale), which thus demonstrated a greater effectiveness of DBS for MC patients than for NC patients. However, the Hoehn and Yahr scale (H and Y Scale) showed the same significance in a situation of stimulation for MC and NC patients. In this later group, the best scores of UPDRS-III were observed for patients with the Parkin mutation before they underwent surgery. CONCLUSIONS: This study shows that surgical treatment probably has a more significant impact on LRRK2 G2019S MC than on idiopathic patients. PMID- 26831336 TI - Posterior composites and new caries on adjacent surfaces - any association? Longitudinal study with a split-mouth design. AB - BACKGROUND: The aim of this longitudinal study was to compare caries incidence in sound approximal surfaces adjacent to newly placed composite restorations with the caries incidence in corresponding surfaces in contralateral teeth without any restorations in contact; and to assess risk factors for dentine caries development on adjacent and control surfaces. METHODS: Data from a practice-based study, where 4030 posterior approximal restorations placed in permanent teeth by clinicians working in a Public Dental Health Service in Norway, were used. The study was approved by the Regional Committee for Medical Research Ethics. The present study is based on a subsample of patients with a sound surface adjacent to a newly placed composite posterior approximal restoration. All individuals who had intact corresponding contralateral pairs of teeth in the same jaw, were included. At the end of the follow-up period, the study restorations and their adjacent surfaces were evaluated clinically and radiographically. Status of the contralateral tooth pair at baseline and end point was based on recordings from routine dental examinations, retrospectively extracted from the electronic dental records. RESULTS: One hundred and ninety three patients (mean age 15.0 years, SD = 3.4) met the inclusion criteria. The surfaces were followed on average for 4.8 years. Follow-up observations revealed that 41 % of adjacent surfaces remained sound, compared with 67 % of the control surfaces (p < 0.001). Restorations were placed in 17 % of adjacent surfaces, compared with 3 % of the control surfaces (p < 0.001). In multivariate logistic regression analysis adjacent surfaces in maxillary teeth had increased risk for dentine caries development (OR 3.1, CI 1.3 7.3). CONCLUSIONS: Caries incidence in intact approximal surfaces adjacent to newly placed composite posterior approximal restorations was significantly higher compared with the contralateral control surface without a restoration in contact. Adjacent surfaces in maxillary teeth had increased risk for dentine caries development. PMID- 26831338 TI - Margaret McCartney: Technology isn't enough. PMID- 26831337 TI - Inflammation-driven bone formation in a mouse model of ankylosing spondylitis: sequential not parallel processes. AB - BACKGROUND: Ankylosing spondylitis (AS) is an immune-mediated arthritis particularly targeting the spine and pelvis and is characterised by inflammation, osteoproliferation and frequently ankylosis. Current treatments that predominately target inflammatory pathways have disappointing efficacy in slowing disease progression. Thus, a better understanding of the causal association and pathological progression from inflammation to bone formation, particularly whether inflammation directly initiates osteoproliferation, is required. METHODS: The proteoglycan-induced spondylitis (PGISp) mouse model of AS was used to histopathologically map the progressive axial disease events, assess molecular changes during disease progression and define disease progression using unbiased clustering of semi-quantitative histology. PGISp mice were followed over a 24 week time course. Spinal disease was assessed using a novel semi-quantitative histological scoring system that independently evaluated the breadth of pathological features associated with PGISp axial disease, including inflammation, joint destruction and excessive tissue formation (osteoproliferation). Matrix components were identified using immunohistochemistry. RESULTS: Disease initiated with inflammation at the periphery of the intervertebral disc (IVD) adjacent to the longitudinal ligament, reminiscent of enthesitis, and was associated with upregulated tumor necrosis factor and metalloproteinases. After a lag phase, established inflammation was temporospatially associated with destruction of IVDs, cartilage and bone. At later time points, advanced disease was characterised by substantially reduced inflammation, excessive tissue formation and ectopic chondrocyte expansion. These distinct features differentiated affected mice into early, intermediate and advanced disease stages. Excessive tissue formation was observed in vertebral joints only if the IVD was destroyed as a consequence of the early inflammation. Ectopic excessive tissue was predominantly chondroidal with chondrocyte-like cells embedded within collagen type II- and X-rich matrix. This corresponded with upregulation of mRNA for cartilage markers Col2a1, sox9 and Comp. Osteophytes, though infrequent, were more prevalent in later disease. CONCLUSIONS: The inflammation-driven IVD destruction was shown to be a prerequisite for axial disease progression to osteoproliferation in the PGISp mouse. Osteoproliferation led to vertebral body deformity and fusion but was never seen concurrent with persistent inflammation, suggesting a sequential process. The findings support that early intervention with anti-inflammatory therapies will be needed to limit destructive processes and consequently prevent progression of AS. PMID- 26831339 TI - A computational model of flow and species transport in the mesangium. AB - A variety of macromolecules accumulate in the glomerular mesangium in many different diseases, but the physics of the transport of these molecules within the mesangial matrix has not been extensively studied. We present a computational model of convection and diffusion within the porous mesangial matrix and apply this model to the specific instance of immunoglobulin A (IgA) transport in IgA nephropathy. We examine the influence of physiological factors including glomerular basement membrane (GBM) thickness and mesangial matrix density on the total accumulation of IgA. Our results suggest that IgA accumulation can be understood by relating convection and diffusion, thus demonstrating the importance of intrinsic glomerular factors. PMID- 26831341 TI - Acoustic Cluster Therapy: In Vitro and Ex Vivo Measurement of Activated Bubble Size Distribution and Temporal Dynamics. AB - Acoustic cluster technology (ACT) is a two-component, microparticle formulation platform being developed for ultrasound-mediated drug delivery. Sonazoid microbubbles, which have a negative surface charge, are mixed with micron-sized perfluoromethylcyclopentane droplets stabilized with a positively charged surface membrane to form microbubble/microdroplet clusters. On exposure to ultrasound, the oil undergoes a phase change to the gaseous state, generating 20- to 40-MUm ACT bubbles. An acoustic transmission technique is used to measure absorption and velocity dispersion of the ACT bubbles. An inversion technique computes bubble size population with temporal resolution of seconds. Bubble populations are measured both in vitro and in vivo after activation within the cardiac chambers of a dog model, with catheter-based flow through an extracorporeal measurement flow chamber. Volume-weighted mean diameter in arterial blood after activation in the left ventricle was 22 MUm, with no bubbles >44 MUm in diameter. After intravenous administration, 24.4% of the oil is activated in the cardiac chambers. PMID- 26831342 TI - Breast Density Analysis with Automated Whole-Breast Ultrasound: Comparison with 3 D Magnetic Resonance Imaging. AB - In this study, a semi-automatic breast segmentation method was proposed on the basis of the rib shadow to extract breast regions from 3-D automated whole-breast ultrasound (ABUS) images. The density results were correlated with breast density values acquired with 3-D magnetic resonance imaging (MRI). MRI images of 46 breasts were collected from 23 women without a history of breast disease. Each subject also underwent ABUS. We used Otsu's thresholding method on ABUS images to obtain local rib shadow information, which was combined with the global rib shadow information (extracted from all slice projections) and integrated with the anatomy's breast tissue structure to determine the chest wall line. The fuzzy C means classifier was used to extract the fibroglandular tissues from the acquired images. Whole-breast volume (WBV) and breast percentage density (BPD) were calculated in both modalities. Linear regression was used to compute the correlation of density results between the two modalities. The consistency of density measurement was also analyzed on the basis of intra- and inter-operator variation. There was a high correlation of density results between MRI and ABUS (R(2) = 0.798 for WBV, R(2) = 0.825 for PBD). The mean WBV from ABUS images was slightly smaller than the mean WBV from MR images (MRI: 342.24 +/- 128.08 cm(3), ABUS: 325.47 +/- 136.16 cm(3), p < 0.05). In addition, the BPD calculated from MR images was smaller than the BPD from ABUS images (MRI: 24.71 +/- 15.16%, ABUS: 28.90 +/- 17.73%, p < 0.05). The intra-operator and inter-operator variant analysis results indicated that there was no statistically significant difference in breast density measurement variation between the two modalities. Our results revealed a high correlation in WBV and BPD between MRI and ABUS. Our study suggests that ABUS provides breast density information useful in the assessment of breast health. PMID- 26831340 TI - Impact of nitric-oxide-mediated vasodilation and oxidative stress on renal medullary oxygenation: a modeling study. AB - The goal of this study was to investigate the effects of nitric oxide (NO) mediated vasodilation in preventing medullary hypoxia, as well as the likely pathways by which superoxide (O2(-)) conversely enhances medullary hypoxia. To do so, we expanded a previously developed mathematical model of solute transport in the renal medulla that accounts for the reciprocal interactions among oxygen (O2), NO, and O2(-) to include the vasoactive effects of NO on medullary descending vasa recta. The model represents the radial organization of the vessels and tubules, centered around vascular bundles in the outer medulla and collecting ducts in the inner medulla. Model simulations suggest that NO helps to prevent medullary hypoxia both by inducing vasodilation of the descending vasa recta (thus increasing O2 supply) and by reducing the active sodium transport rate (thus reducing O2 consumption). That is, the vasodilative properties of NO significantly contribute to maintaining sufficient medullary oxygenation. The model further predicts that a reduction in tubular transport efficiency (i.e., the ratio of active sodium transport per O2 consumption) is the main factor by which increased O2(-) levels lead to hypoxia, whereas hyperfiltration is not a likely pathway to medullary hypoxia due to oxidative stress. Finally, our results suggest that further increasing the radial separation between vessels and tubules would reduce the diffusion of NO towards descending vasa recta in the inner medulla, thereby diminishing its vasoactive effects therein and reducing O2 delivery to the papillary tip. PMID- 26831343 TI - Identification of the Position and Thickness of the First Annular Pulley in Sonographic Images. AB - The purpose was to identify the A1 pulley's exact location and thickness by comparing measurements from a clinical high-frequency ultrasound scanner system (CHUS), a customized high-frequency ultrasound imaging research system (HURS) and a digital caliper. Ten cadaveric hands were used. We explored the pulley by layers, inserted guide pins and scanned it with the CHUS. After identifying the pulley, we measured each long finger's thickness using the CHUS and excised the pulley to measure its thickness with a digital caliper and the HURS. The thin hypo-echoic layer was revealed to be the synovial fluid space, and the pulley appears hyper-echoic regardless of scan direction. We also defined the pulley's boundaries. Moreover, the CHUS provided a significantly lower measurement of the pulley's thickness than the digital caliper and HURS. Likewise, based on the digital caliper's measurement, the HURS had significantly lower mean absolute and relative errors than the CHUS. PMID- 26831345 TI - [The place of inhaled corticosteroids in COPD]. AB - INTRODUCTION: Clinical trials have provided some evidence of a favorable effect of inhaled corticosteroids on the frequency of exacerbations and on the quality of life of patients with chronic obstructive pulmonary disease (COPD). In contrast, ICS have little or no impact on lung function decline and on mortality. STATE OF THE ART: Inhaled corticosteroids are recommended only in a minority of COPD patients, those with severe disease and repeated exacerbations and probably those with the COPD and asthma overlap syndrome. However, surveys indicate that these drugs are inappropriately prescribed in a large population of patients with COPD. Overtreatment with inhaled corticosteroids exposes these patients to an increased risk of potentially severe side-effects such as pneumonia, osteoporosis, and oropharyngeal candidiasis. Moreover, it represents a major waste of health-care spending. CONCLUSION: Primary care physicians as well as pulmonologists should be better aware of the benefits as well as the side-effects and costs of inhaled corticosteroids. PMID- 26831347 TI - The search for causal traits of speciation: Divergent female mate preferences target male courtship song, not pheromones, in Drosophila athabasca species complex. AB - Understanding speciation requires the identification of traits that cause reproductive isolation. This remains a major challenge since it is difficult to determine which of the many divergent traits actually caused speciation. To overcome this difficulty, we studied the sexual cue traits and behaviors associated with rapid speciation between EA and WN sympatric behavioral races of Drosophila athabasca that diverged only 16,000-20,000 years ago. First, we found that sexual isolation was essentially complete and driven primarily by divergent female mating preferences. To determine the target of female mate choice, we found that, unlike cuticular hydrocarbons (CHCs), male courtship song is highly divergent between EA and WN in both allopatry and sympatry and is not affected by latitudinal variation. We then used pheromone rub-off experiments to show no effect of CHCs on divergent female mate choice. In contrast, both male song differences and male mating success in hybrids exhibited a large X-effect and playback song experiments confirmed that male courtship song is indeed the target of sexual isolation. These results show that a single secondary sexual trait is a major driver of speciation and suggest that we may be overestimating the number of traits involved in speciation when we study older taxa. PMID- 26831349 TI - Disease genetics: Prion variant pathogenicity through large-scale population sequencing. PMID- 26831352 TI - Social Bayes: Using Bayesian Modeling to Study Autistic Trait-Related Differences in Social Cognition. AB - BACKGROUND: Autism is characterized by impairments of social interaction, but the underlying subpersonal processes are still a matter of controversy. It has been suggested that the autistic spectrum might be characterized by alterations of the brain's inference on the causes of socially relevant signals. However, it is unclear at what level of processing such trait-related alterations may occur. METHODS: We used a reward-based learning task that requires the integration of nonsocial and social cues in conjunction with computational modeling. Healthy subjects (N = 36) were selected based on their Autism Quotient Spectrum (AQ) score, and AQ scores were assessed for correlations with model parameters and task scores. RESULTS: Individual differences in AQ were inversely correlated with participants' task scores (r = -.39, 95% confidence interval [CI] [-.68, -.13]). Moreover, AQ scores were significantly correlated with a social weighting parameter that indicated how strongly the decision was influenced by the social cue (r = -.42, 95% CI [-.66, -.19]), but not with other model parameters. Also, more pronounced social weighting was related to higher scores (r = .50, 95% CI [.20, .86]). CONCLUSIONS: Our results demonstrate that higher autistic traits in healthy subjects are related to lower scores in a learning task that requires social cue integration. Computational modeling further demonstrates that these trait-related performance differences are not explained by an inability to process the social stimuli and its causes, but rather by the extent to which participants take into account social information during decision making. PMID- 26831353 TI - Hospital Care Efficiency and the SMART (Specific, Measurable, Agreed, Required, and Timely) Medicine Initiative. PMID- 26831354 TI - Letter to the editor. PMID- 26831355 TI - Heterogeneity in endoscopic treatment of Crohn's disease-associated strictures: An international inflammatory bowel disease specialist survey. AB - BACKGROUND: Crohn's disease (CD) is frequently complicated by intestinal strictures, which are commonly treated by endoscopic balloon dilation (EBD). However, available data on this area of treatment is limited. The aim of this study was to depict the heterogeneity of endoscopic management of CD-associated strictures among international CD specialists to identify common treatment standards. METHODS: IBD experts of the International Organization for the Study of Inflammatory Bowel Disease (IOIBD), the European Crohn's and Colitis Organization (ECCO), and from the Prospective Value In IBD trials (PROVIT) completed a web-based questionnaire to evaluate their endoscopic experience, practice setting, and number of EBDs performed annually. Additionally, two case scenarios and technical practice parameters were investigated. RESULTS: A total of 126 subjects from 15 countries completed the survey. The maximal length of dilated stricture was 4.5 +/- 1.7 cm. The most commonly used maximal balloon size was graded as 15-18 mm. While 87.2 % of the participants favored EBD for anastomotic strictures, only 58.6 % did so in the case of naive strictures. Only 35.7 % of physicians dilated actively inflamed strictures. Interventional endoscopists were more likely to dilate only clinically symptomatic strictures (p = 0.046). Surgeons favored surgical treatment of de novo ileocecal strictures compared to gastroenterologists (p = 0.026), reported a shorter stricture length being amendable by EBD (p = 0.045), and more frequently used concomitant therapies (p = 0.001). Operator experience increased the likelihood of EBD use in actively inflamed strictures (p = 0.002), maximum length of stricture, and maximum balloon size (p = 0.001). CONCLUSIONS: EBD is a widely used treatment approach for stricturing CD. Individual approaches differ significantly based on background of the operator, experience level, and practice setting. PMID- 26831357 TI - Relationship between somatosensory deficit and brain somatosensory system after early brain lesion: A morphometric study. AB - Cerebral Palsy (CP) is a group of permanent motor disorders due to non progressive damage to the developing brain. Poor tactile discrimination is common in children with unilateral CP. Previous findings suggest the crucial role of structural integrity of the primary (S1) and secondary (S2) somatosensory areas located in the ipsilesional hemisphere for somatosensory function processing. However, no focus on the relationship between structural characteristics of ipsilesional S1 and S2 and tactile discrimination function in paretic hands has been proposed. Using structural MRI and a two-point discrimination assessment (2 PD), we explore this potential link in a group of 21 children (mean age 13 years and 7 months) with unilateral CP secondary to a periventricular white matter injury (PWMI) or middle cerebral artery infarct (MCA). For our whole sample there was a significant negative correlation between the 2 PD and the gray matter volume in the ipsilesional S2 (rho = -0.50 95% confidence interval [-0.76, 0.08], one-tailed p-value = 0.0109) and in the ipsilesional S1 (rho = -0.57, 95% confidence interval [-0.81, -0.19], one-tailed p-value = 0.0032). When studying these relationships with regard to the lesion types, we found these correlations were non-significant in the patients with PWMI but stronger in patients with MCA. According to our results, the degree of sensory impairment is related to the spared gray matter volume in ipsilesional S1 and S2 and is marked after an MCA stroke. Our work contributes to a better understanding of why some patients with CP have variable somatosensory deficit following an early brain lesion. PMID- 26831356 TI - Nationwide prospective and retrospective surveys for hepatitis B virus reactivation during immunosuppressive therapies. AB - BACKGROUND: The significance of HBV reactivation during immunosuppressive therapy was evaluated in three nationwide cohorts including patients with previously resolved HBV (prHBV) infection. METHODS: The clinical features of 1061 patients with acute liver failure (ALF) or late-onset hepatic failure (LOHF) were retrospectively examined, focusing on those who experienced HBV reactivation. Additionally, 420 patients with prHBV infection were prospectively enrolled: 203 received immunosuppressive therapies immediately after enrollment, while the remaining 217 were enrolled after having received immunosuppressive therapies without the occurrence of HBV reactivation. The serum HBV-DNA levels were prospectively monitored every month, and the incidences of HBV reactivation, defined as a serum HBV-DNA level of 1.3 log IU/ml or more, were evaluated. RESULTS: In the retrospective study, persistent HBV infection was found in 90 patients, and HBV reactivation was responsible for liver injuries in 50 patients including 23 receiving immunosuppressive therapies (26 with HBs-antigen positivity, 7 with prHBV infection). None of seven patients with prHBV infection were rescued. In the prospective studies, HBV reactivation occurred in ten patients, but preemptive entecavir administration prevented liver injury. The cumulative reactivation rate was 3.2 % at 6 months, and the increase of the rate compared to that at 6 months was +1.5 % at 48 months. CONCLUSIONS: HBV reactivation during immunosuppression was responsible for liver injuries in a quarter of the ALF/LOHF patients with persistent HBV infection. Early serum HBV DNA monitoring may improve patient prognosis, since HBV reactivation typically occurs within 6 months of the start of immunosuppressive therapies in patients with prHBV infection. PMID- 26831358 TI - Arthropod predation in a dendrobatid poison frog: does frog life stage matter? AB - Frogs in the family Dendrobatidae are well known for their conspicuous colors and variable alkaloid-based chemical defenses. The aposematic coloration in dendrobatid frogs appears to deter predators with color vision, but relatively little is known about how these frogs are protected and their defenses are perceived by non-color vision dominated predators. The neotropical bullet ant Paraponera clavata and the red-legged banana spider Cupiennius coccineus are predators that avoid adults of the dendrobatid Oophaga pumilio, but readily consume non-toxic frogs. Juvenile O. pumilio possess the same warning coloration as adult O. pumilio, but may be more palatable given that they have lower quantities of defensive chemicals. This may provide juvenile O. pumilio protection from color-sighted predators, while leaving them susceptible to predators that use chemoreception. To test this hypothesis, we presented juveniles and adults of both O. pumilio and the non-chemically defended frog Craugastor bransfordii to bullet ants and banana spiders. Both bullet ants and banana spiders preyed upon C. bransfordii significantly more than on O. pumilio. Adult and juvenile C. bransfordii experienced similar predation rates by both predators. The life stage of O. pumilio significantly predicted predation by bullet ants, with juveniles being consumed significantly more often than adults. However, the life stage of O. pumilio did not predict predation by banana spiders, as no adults or juveniles were consumed. Our study provides evidence that bullet ants can detect differences in chemical defenses between juvenile and adult O. pumilio, resulting in differential predation on the more palatable juvenile frogs. The avoidance of both adults and juveniles by C. coccineus suggests the alkaloids in O. pumilio act as an effective chemical deterrent to banana spiders, regardless of quantity. Overall, our results suggest that differences in alkaloid defenses among life stages in O. pumilio correspond to differences in relative palatability to at least one arthropod predator. PMID- 26831359 TI - Carbon dioxide detection in adult Odonata. AB - The present paper shows, by means of single-cell recordings, responses of antennal sensory neurons of the damselfly Ischnura elegans when stimulated by air streams at different CO2 concentrations. Unlike most insects, but similarly to termites, centipedes and ticks, Odonata possess sensory neurons strongly inhibited by CO2, with the magnitude of the off-response depending upon the CO2 concentration. The Odonata antennal sensory neurons responding to CO2 are also sensitive to airborne odors; in particular, the impulse frequency is increased by isoamylamine and decreased by heptanoic and pentanoic acid. Further behavioral investigations are necessary to assign a biological role to carbon dioxide detection in Odonata. PMID- 26831360 TI - Factors Associated With 8-Year Mortality in Older Patients With Cerebral Small Vessel Disease: The Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) Study. AB - IMPORTANCE: Gait and cognition have been related to mortality in population-based studies. This association is possibly mediated by cerebral small vessel disease (SVD), which has been associated with mortality as well. It is unknown which factors can predict mortality in individuals with SVD. Identification of high risk patients may provide insight into factors that reflect their vital health status. OBJECTIVES: To assess mortality in patients with cerebral SVD and identify potential clinical and/or imaging factors associated with mortality. DESIGN, SETTING, AND PARTICIPANTS: A prospective, single-center cohort study was conducted. The present investigation is embedded in the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) study. Between January 17, 2006, and February 27, 2007, all participants underwent a cognitive and motor assessment and cerebral magnetic resonance imaging (MRI) including a diffusion tensor imaging sequence to assess microstructural integrity of the white matter. Participants were followed up until their death or November 24, 2014. Participants included 503 older adults with SVD noted on brain imaging. Data analysis was performed from November 26, 2014, to February 2, 2015. MAIN OUTCOMES AND MEASURES: Eight-year all-cause mortality. RESULTS: Of 503 participants (mean [SD] age, 65.7 [8.8] years; range, 50-85 years; 284 [56.5%] were male), 80 individuals (15.9%) died during a mean (SD) follow-up of 7.8 (1.5) years. In the final analysis, 494 (98.2%) were included, of whom 78 (15.8%) died. Gait speed, cognitive index, conventional MRI markers of SVD (white matter hyperintensity volume, brain volume, and lacunes), and diffusion measures of the white matter were associated with an 8-year risk of mortality independent of age, sex, and vascular risk factors. The prediction of mortality was determined using Cox proportional hazards models with backward stepwise selection and including age, sex, vascular risk factors, gait speed, cognitive index, MRI, and diffusion measures. Results are reported as hazard ratios (HRs) (95% CI). Older age (1.05 per 1-year increase [1.01-1.08]), lower gait speed (1.15 per 0.1-m/s slower gait [1.06-1.24]), lower gray matter volume (0.72 per 1-SD increase [0.55-0.95]), and greater global mean diffusivity of the white matter (1.51 per 1-SD increase [1.19 1.92]) were identified as the main factors associated with mortality. Cognitive index and other conventional SVD markers were not retained in the prediction model. CONCLUSIONS AND RELEVANCE: Gait, cognition, and imaging markers of SVD are associated with 8-year risk of mortality. In the prediction of mortality, an older age, lower gait speed, lower gray matter volume, and greater global mean diffusivity of white matter at baseline best predicted mortality in our population. Further research is needed to investigate the reproducibility of this prediction model and to elucidate the association between the factors identified and mortality. PMID- 26831361 TI - How have the recent advances in antiviral therapy impacted the management of virus-related hepatocellular carcinoma? AB - INTRODUCTION: Whether the recent advances in antiviral therapy including nucleos(t)ide analogue (NA) or interferon (IFN) impacts the management of patients with virus-related hepatocellular carcinoma (HCC) remains unclear. AREA COVERED: The beneficial effects of antiviral therapy on HCC patients receiving curative treatment, transhepatic arterial chemoembolization (TACE), or radiotherapy are reviewed and discussed. EXPERT OPINION: For patients with HCV related HCC after curative treatment, interferon (IFN)-based therapy has been shown to improve the survival and reduces the risk of HCC recurrence. However, it carries the risk of adverse effects, especially in cirrhotic patients. Therefore, the benefit of IFN should be weighted against its risk in each individual. For patients with HBV-related HCC after curative treatments, antiviral treatment with NA has been found to improve liver function, overall survival, and possibly reduce the risk of HCC recurrence. In contrast, these benefits were not consistently observed in those receiving IFN treatment. In HCC patients receiving palliative TACE or radiotherapy, HBV reactivation occurs in a small proportion of them, and preemptive NA treatment can reduce the risk of hepatitis flare due to viral reactivation. Therefore, NA treatment after curative treatments or TACE is strongly recommended for HCC patients with high viral load (HBV DNA> 2000 IU/mL). PMID- 26831362 TI - Strain effects on the work function of an organic semiconductor. AB - Establishing fundamental relationships between strain and work function (WF) in organic semiconductors is important not only for understanding electrical properties of organic thin films, which are subject to both intrinsic and extrinsic strains, but also for developing flexible electronic devices. Here we investigate tensile and compressive strain effects on the WF of rubrene single crystals. Mechanical strain induced by thermal expansion mismatch between the substrate and rubrene is quantified by X-ray diffraction. The corresponding WF change is measured by scanning Kelvin probe microscopy. The WF of rubrene increases (decreases) significantly with in-plane tensile (compressive) strain, which agrees qualitatively with density functional theory calculations. An elastic-to-plastic transition, characterized by a steep rise of the WF, occurs at ~0.05% tensile strain along the rubrene pi-stacking direction. The results provide the first concrete link between mechanical strain and WF of an organic semiconductor and have important implications for understanding the connection between structural and electronic disorder in soft organic electronic materials. PMID- 26831365 TI - The Inseparable Histories of the Southern Surgical Association and Surgery for Portal Hypertension. PMID- 26831364 TI - "Can't you initiate me here?": Challenges to timely initiation on antiretroviral therapy among methadone clients in Dar es Salaam, Tanzania. AB - BACKGROUND: Despite dramatic improvement in antiretroviral therapy (ART) access globally, people living with HIV who inject drugs continue to face barriers that limit their access to treatment. This paper explores barriers and facilitators to ART initiation among clients attending a methadone clinic in Dar es Salaam, Tanzania. METHODS: We interviewed 12 providers and 20 clients living with HIV at the Muhimbili National Hospital methadone clinic between January and February 2015. We purposively sampled clients based on sex and ART status and providers based on job function. To analyze interview transcripts, we adopted a content analysis approach. RESULTS: Participants identified several factors that hindered timely ART initiation for clients at the methadone clinic. These included delays in CD4 testing and receiving CD4 test results; off-site HIV clinics; stigma operating at the individual, social and institutional levels; insufficient knowledge of the benefits of early ART initiation among clients; treatment breakdown at the clinic level possibly due to limited staff; and initiating ART only once one feels physically ill. Participants perceived social support as a buffer against stigma and facilitator of HIV treatment. Some clients also reported that persistent monitoring and follow-up on their HIV care and treatment by methadone clinic providers led them to initiate ART. CONCLUSION: Health system factors, stigma and limited social support pose challenges for methadone clients living with HIV to initiate ART. Our findings suggest that on-site point-of-care CD4 testing, a peer support system, and trained HIV treatment specialists who are able to counsel HIV-positive clients and initiate them on ART at the methadone clinic could help reduce barriers to timely ART initiation for methadone clients. PMID- 26831366 TI - RETRACTED: Impact of Cooperative Trial and Sociodemographic Variation on Adjuvant Radiation Therapy Usage in Elderly Women (>=70 Years) with Stage I, Estrogen Receptor-Positive Breast Cancer: Analysis of the National Cancer Data Base. AB - BACKGROUND: The Cancer and Leukemia Group B (CALGB) 9343 trial demonstrated that adjuvant radiation therapy (RT) can be omitted in women aged 70 years or older, with small, estrogen receptor (ER)+ breast cancer. We postulated that RT usage after CALGB's publication should have decreased over time. STUDY DESIGN: We evaluated a cohort of 205,860 women aged 70 years or older, with stage I, ER+/progesterone receptor (PR)+ breast cancer with lumpectomy, diagnosed between 1998 and 2012, in the National Cancer Data Base. Clinicopathologic and sociodemographic variables were compared between pre-CALGB and post-CALGB publication (circa 2004). Univariate and multivariate analysis were used. RESULTS: Radiation therapy usage decreased by only 2.95% after CALGB publication (68.71% vs 65.76%; p < 0.0001). Almost one-third of women with short life expectancy (>=85 years) received RT in the post-CALGB group. Significant predictors (p < 0.01) of lowest RT use include advanced age, increased great circle distance, academic research program, East South Central region, rural population < 2,500 not adjacent to a metropolitan area, low income level, high comorbidity index, small tumor, well-differentiated histology, residual tumor, and lack of receipt of anti-hormonal therapy. CONCLUSIONS: The CALGB trial had a minimal impact on the rate of adjuvant RT use among elderly women with small, hormone positive breast cancers. Significant variation in RT usage exists across sociodemographic strata. PMID- 26831367 TI - Evaluation of a dedicated brain metastases treatment planning optimization for radiosurgery: a new treatment paradigm? AB - PURPOSE: To investigate the feasibility of a novel dedicated treatment planning solution, to automatically target multiple brain metastases with a single isocenter and multiple inversely-optimized dynamic conformal arcs (DCA), and to benchmark it against the well-established multiple isocenter DCA (MIDCA) and volumetric modulated arc therapy (VMAT) approaches. MATERIAL AND METHODS: Ten previously treated patients were randomly selected, each representing a variable number of lesions ranging between 1 to 8. The original MIDCA treatments were replanned with both VMAT and the novel brain metastases tool. The plans were compared by means of Paddick conformity (CI) and gradient index (GI), and the volumes receiving 10 Gy (V10) and 12 Gy (V12). RESULTS: The brain metastases software tool generated plans with similar CI (0.65 +/- 0.08) as both established treatment techniques while improving the gradient (mean GI = 3.9 +/- 1.4). The normal tissue exposure in terms of V10 (48.5 +/- 35.9 cc) and V12 (36.3 +/- 27.1 cc) compared similarly to the MIDCA technique and surpassed VMAT plans. CONCLUSIONS: The automated brain metastases planning algorithm software is an optimization of DCA radiosurgery by increasing delivery efficiency to the level of VMAT approaches. Improving dose gradients and normal tissue sparing over VMAT, revives DCA as the paradigm for linac-based stereotactic radiosurgery of multiple brain metastases. PMID- 26831368 TI - Genome-wide screening identifies a KCNIP1 copy number variant as a genetic predictor for atrial fibrillation. AB - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Previous genome-wide association studies had identified single-nucleotide polymorphisms in several genomic regions to be associated with AF. In human genome, copy number variations (CNVs) are known to contribute to disease susceptibility. Using a genome-wide multistage approach to identify AF susceptibility CNVs, we here show a common 4,470-bp diallelic CNV in the first intron of potassium interacting channel 1 gene (KCNIP1) is strongly associated with AF in Taiwanese populations (odds ratio=2.27 for insertion allele; P=6.23 * 10(-24)). KCNIP1 insertion is associated with higher KCNIP1 mRNA expression. KCNIP1-encoded protein potassium interacting channel 1 (KCHIP1) is physically associated with potassium Kv channels and modulates atrial transient outward current in cardiac myocytes. Overexpression of KCNIP1 results in inducible AF in zebrafish. In conclusions, a common CNV in KCNIP1 gene is a genetic predictor of AF risk possibly pointing to a functional pathway. PMID- 26831369 TI - Low-dose carbon-based nanoparticle-induced effects in A549 lung cells determined by biospectroscopy are associated with increases in genomic methylation. AB - Nanotechnology has introduced many manufactured carbon-based nanoparticles (CNPs) into our environment, generating a debate into their risks and benefits. Numerous nanotoxicology investigations have been carried, and nanoparticle-induced toxic effects have been reported. However, there remain gaps in our knowledge, primarily regarding mechanism. Herein, we assessed the global alterations induced by CNPs in A549 lung cells using biospectroscopy techniques, including attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy and surface enhanced Raman spectroscopy (SERS). A549 cells were treated with fullerene (C60), long or short multi-walled carbon nanotubes, or single-walled carbon nanotubes at concentrations of 0.1 mg/L, 0.01 mg/L and 0.001 mg/L. Exposed cells were then analysed by ATR-FTIR spectroscopy and SERS. Spectra were pre-processed via computational analysis, and information on biochemical alterations in exposed cells were identified. Additionally, global DNA methylation levels in cells exposed to CNPs at 0.1 mg/L were determined using HPLC-MS and genetic regulators (for DNA methylation) were checked by quantitative real-time RT-PCR. It was found that CNPs exert marked effects in A549 cells and also contribute to increases in global DNA methylation. For the first time, this study highlights that real-world levels of nanoparticles can alter the methylome of exposed cells; this could have enormous implications for their regulatory assessment. PMID- 26831370 TI - Longitudinal metabolic imaging of hepatocellular carcinoma in transgenic mouse models identifies acylcarnitine as a potential biomarker for early detection. AB - The cumulative effects of hepatic injury due to hepatitis B virus (HBV) infections and aflatoxin-B1 (AFB1) exposure are the major risk factors of HCC. Understanding early metabolic changes involving these risk factors in an animal model closely resembling human hepatocellular carcinoma (HCC) is critical for biomarker discovery and disease therapeutics. We have used the hepatitis B surface antigen (HBsAg) transgenic mouse model that mimics HBV carriers with and without AFB1 treatment. We investigated early metabolic changes from preneoplastic state to HCC by non-invasive longitudinal imaging in three HCC groups of mice: HBsAg + AFB1(Gp-I), AFB1 alone (Gp-II), HBsAg alone (Gp-III) and a control group (wild-type untreated; Gp-IV). For the first time, we have identified acylcarnitine signals in vivo in the liver prior to the histological manifestation of the tumors in all three groups. Acylcarnitine concentration increased with increase in tumor growth in all HCC mouse models, indicating elevated metabolic activity and increased cell turnover. This was confirmed in a pilot study using human serum from HCC patients, which revealed a higher concentration of acylcarnitine compared with normal subjects. Translational clinical studies can be designed to detect acylcarnitine in patients with high risk factors for HCC. PMID- 26831371 TI - Distinctive origin of artemisinin-resistant Plasmodium falciparum on the China Myanmar border. AB - The artemisinin (ART), discovered in China, has been widely used against malaria in China over the last 30 years. Understanding the emergence and origin of ART resistance in China is therefore of great interest. We analyzed 111 culture adapted isolates of P. falciparum from China-Myanmar (CM) border for their susceptibility to dihydroartemisinin using the ring stage survival assay (RSA0 3h) and genotyped their K13 genes. Of the isolates, 59 had a wild type of the K13 marker and a median ring survival rate of 0.26% (P95 = 1.005%). Among the remaining isolates harboring single mutations in the K13 marker, 26 survived at >P95(median survival rate = 2.95%). Further, we genotyped the K13 gene of 693 isolates collected from different regions in China and China-Myanmar/Thai Cambodia/Thai-Myanmar (CM/TC/TM) borders, 308 (44.4%) had K13 mutations and marked differences in the patterns of K13 mutations were observed between the CM and the TC/TM borders. A network diagram showed that majority of the K13 mutant alleles from the CM border clustered together including those harboring the high resistant-associated R539T mutations. The resistant parasites carrying distinct halplotypes suggested the multiple indigenous origins of the resistant alleles, which highlight the importance of surveillance of resistance in all malaria endemic areas where ART has been introduced. PMID- 26831372 TI - Can we engage caregiver spouses of patients with heart failure with a low intensity, symptom-guided intervention? AB - OBJECTIVE: Evaluate a pilot intervention to engage caregivers in management of heart failure (HF) patient symptoms. BACKGROUND: HF impairs quality of life; caregivers provide an important role in HF management. METHODS: We developed modules to help patients report and caregivers alleviate symptoms of depression, pain, dyspnea, and fatigue. Semi-structured interviews followed by a mixed inductive and deductive, team-based analysis were used to evaluate acceptability and feasibility in patients with HF and their caregivers. RESULTS: Participants (n = 22) expressed significant interest but few used the modules in follow-up. We identified three barriers to acceptability and feasibility: the quality of dyadic relationship, the timing and structure of the intervention, and the patient's perceived control over their illness. CONCLUSIONS: Future interventions should evaluate dyadic relationship dynamics, match the timing and content of the intervention to the patient population, and enroll patients with perceived control over their illness to maximize intervention acceptability and feasibility. PMID- 26831373 TI - Parents' experiences of having a child undergoing congenital heart surgery: An emotional rollercoaster from shocking to blessing. AB - OBJECTIVES: To describe parents' experiences when their child with congenital heart disease (CHD) underwent heart surgery. BACKGROUND: About 40,000 children are born with CHD in the United States each year. Very few studies have explored parents' experiences when their child was diagnosed with CHD and underwent heart surgery. METHODS: Descriptive phenomenology informed this study that consisted of two interviews with 13 parents. RESULTS: Parents experienced a "rollercoaster" of emotions. Critical times were when parents received their child's diagnosis, handed their child over to the surgical team, and visited their child in the pediatric intensive care unit after surgery. Related stressors were the uncertainty of outcomes after surgery, the loss of parental control, the physical appearance of their child, and the fear of the technological atmosphere in the intensive care unit. CONCLUSIONS: The ups and downs of parents' emotions reflected their child's changing condition and parents' adjustment to the condition. PMID- 26831374 TI - A systematic review of transitional-care strategies to reduce rehospitalization in patients with heart failure. AB - The objective of this review was to evaluate existing transition-of-care models and identify common themes that may minimize exacerbation and rehospitalization, and improve quality of life for patients with heart failure (HF). HF is a significant burden in the United States and a common reason for recurrent hospitalizations. When multidisciplinary health care providers function as liaisons and educators during transition from hospital to home, they help prepare patients for life with chronic HF and mitigate the need for readmission. Systematic literature searches were performed to identify research papers relevant to transition-of-care themes in HF. Eight common themes were identified that can be applied to patients with HF to improve long-term outcomes. This paper emphasizes ways in which health care providers can implement theme-based transitional care, including providing patients and caregivers with practical skills and services that promote knowledge and engagement in self-care and stimulate active communication with health care providers. PMID- 26831376 TI - Covalent Postassembly Modification and Water Adsorption of Pd3 Self-Assembled Trinuclear Barrels. AB - Three new ditopic imidazole ligands (2-4) were synthesized in high yields and characterized by various spectroscopic techniques. These ligands resulted in the formation of [3 + 6] self-assembled trinuclear barrels (5-7) in quantitative yields by stoichiometric combination of individual ligands and Pd(NO3)2 in DMSO. All the three assemblies (5-7) were characterized by (1)H NMR and ESI-MS analysis, and subsequently, structures of the complexes 5 and 6 were confirmed by single-crystal X-ray diffraction studies. Structure analysis reveals the presence of NO3(-) counteranions in the intermolecular channels/pockets, which could potentially act as H-bonding sites between adsorbed water molecules within the channels. In fact, both the assemblies (5 and 6) showed water uptake (136.58, and 123.78 cm(3) g(-1), respectively) at ambient temperature under maximum allowable humidity. In addition, free aldehyde group present in the bridging ligand in complex 7 provides reactive site for postassembly modification. Herein, Knoevenagel condensation with Meldrum's acid was utilized under mild conditions by targeting aldehyde group appended in prefabricated complex 7 and transformed into a different complex (8) with altered functional group. Such postassembly functionalization enables incorporation of a new functional group without disrupting the integrity of the trifacial structure. PMID- 26831375 TI - Preoperative Aspects and Dimensions Used for Anatomical Score Predicts Treatment Failures in Laparoscopic Cryoablation of Small Renal Masses. AB - OBJECTIVES: To determine the potential of the preoperative aspects and dimensions used for anatomical (PADUA) classification score as a predictive tool in relation to residual unablated tumor and disease-free survival (DFS) following laparoscopy assisted cryoablation (LCA) of small renal masses. PATIENTS AND METHODS: A multi institutional cohort of 212 patients with biopsy-verified T1N0M0 renal malignancies treated with LCA between August 2005 and September 2014 were retrospectively investigated with respect to oncologic outcomes. RESULTS: The preoperative PADUA score was found to be low (6-7 points) in 70 patients (33%), moderate (8-9 points) in 86 patients (40.6%), and high (10-14 points) in 56 patients (26.4%). The mean PADUA score was significantly higher in cases (n = 11) with residual unablated tumor (10.4 vs 8.1, p < 0.001) and in cases (n = 8) with local tumor recurrence (9.8 vs 8.1, p < 0.001) at a mean follow-up of 37 (95% confidence interval: 34-40) months. The estimated 2-, 3-, and 5-year DFS for patients with a moderate PADUA score was 96%, 94%, and 94% compared with 95%, 87%, and 81%, respectively, for patients with a high PADUA score (log-rank, p = 0.003). The PADUA score did not predict overall survival. CONCLUSION: The PADUA score significantly predicts residual unablated tumor and DFS following LCA. Further studies are needed to validate the efficacy of the PADUA score in relation to oncologic outcomes following ablative procedures. PMID- 26831377 TI - Thermodynamic Constraints in Using AuM (M = Fe, Co, Ni, and Mo) Alloys as N2 Dissociation Catalysts: Functionalizing a Plasmon-Active Metal. AB - The Haber-Bosch process for NH3 synthesis is arguably one of the greatest inventions of the 20th century, with a massive footprint in agriculture and, historically, warfare. Current catalysts for this reaction use Fe for N2 activation, conducted at high temperatures and pressures to improve conversion rate and efficiency. A recent finding shows that plasmonic metal nanoparticles can either generate highly reactive electrons and holes or induce resonant surface excitations through plasmonic decay, which catalyze dissociation and redox reactions under mild conditions. It is therefore appealing to consider AuM (M = Fe, Co, Ni, and Mo) alloys to combine the strongly plasmonic nature of Au and the catalytic nature of M metals toward N2 dissociation, which together might facilitate ammonia production. To this end, through density functional theory, we (i) explore the feasibility of forming these surface alloys, (ii) find a pathway that may stabilize/deactivate surface M substituents during fabrication, and (iii) define a complementary route to reactivate them under operational conditions. Finally, we evaluate their reactivity toward N2, as well as their ability to support a pathway for N2 dissociation with a low thermodynamic barrier. We find that AuFe possesses similar appealing qualities, including relative stability with respect to phase separation, reversibility of Fe oxidation and reduction, and reactivity toward N2. While AuMo achieves the best affinity toward N2, its strong propensity toward oxidation could greatly limit its use. PMID- 26831379 TI - Single additive mechanism predicts lateral interactions effects-computational model. AB - The mechanism underlying the lateral interactions (LI) phenomenon is still an enigma. Over the years, several groups have tried to explain the phenomenon and suggested models to predict its psychophysical results. Most of these models comprise both inhibitory and facilitatory mechanisms for describing the LI phenomenon. Their studies' assumption that a significant inhibition mechanism exists is based on the classical interpretation of the threshold elevation perceived in psychophysical experiments. In this work, we suggest a different interpretation of the threshold elevation obtained experimentally. Our model proposes and demonstrates how a facilitatory additive mechanism can solely predict both the facilitation and "inhibition" aspects of the phenomenon, without the need for an additional inhibitory mechanism, at least for the two flankers' configurations. Though the model is simple it succeeds to predict the LI effect under a large variety of stimuli configurations and parameters. The model is in agreement with both classical and recent psychophysical and neurophysiological results. We suggest that the LI mechanism plays a role in creating an educated guess to form a continuation of gratings and textures based on the surrounding visual stimuli. PMID- 26831378 TI - Stressors in Teens with Type 1 Diabetes and Their Parents: Immediate and Long Term Implications for Transition to Self-Management. AB - Teens with Type 1 diabetes and their parents experience every day and illness related stress; however, understanding of how these stressors relate to the transition to adulthood is limited. The purpose of this study was to identify stressors of teens with Type 1 diabetes (T1DM) and their parents related to the impending transition to adulthood. DESIGN AND METHODS: This study used open-ended questions to identify every day and illness-related stressors among 15 teens with T1DM and 25 parents seen in one pediatric diabetes clinic. Qualitative descriptive analysis identified themes in interview transcripts. RESULTS: The primary teen stressor related to impending transition centered on ineffective self-management, often when they were taking over responsibility for T1DM management. Parents' concerns included immediate and long-term negative outcomes of teen self-management as well as financial resources and health insurance for the teen. Teens and parents both expressed specific concerns about outcomes and prevention of nocturnal hypoglycemia, and identified uncertainties related to teen health and diabetes-focused health care when no longer living in the parent's home. CONCLUSIONS: Teens with Type 1 diabetes and their parents understand that independent teen self-management is a component of transition to adulthood, but worry about teen self-management outcomes. Concerns specific to health care transition included health insurance, T1DM resources, and teens' abilities to handle new situations. PRACTICE IMPLICATIONS: Identifying current and future self-management concerns of individuals and families can facilitate targeted education and interventions to support successful transition to adulthood. PMID- 26831380 TI - Photonic-crystal-based all-optical NOT logic gate. AB - In the present paper, we have utilized the concept of photonic crystals for the implementation of an optical NOT gate inverter. The designed structure has a hexagonal arrangement of silicon rods in air substrate. The logic function is based on the phenomenon of the existence of the photonic bandgap and resulting guided modes in defect photonic crystal waveguides. We have plotted the transmission, extinction ratio, and tolerance analysis graphs for the structure, and it has been observed that the maximum output is obtained for a telecom wavelength of 1.554 MUm. Dispersion curves are obtained using the plane wave expansion method, and the transmission is simulated using the finite element method. The proposed structure is applicable for photonic integrated circuits due to its simple structure and clear operating principle. PMID- 26831381 TI - Single image super-resolution using locally adaptive multiple linear regression. AB - This paper presents a regularized superresolution (SR) reconstruction method using locally adaptive multiple linear regression to overcome the limitation of spatial resolution of digital images. In order to make the SR problem better posed, the proposed method incorporates the locally adaptive multiple linear regression into the regularization process as a local prior. The local regularization prior assumes that the target high-resolution (HR) pixel is generated by a linear combination of similar pixels in differently scaled patches and optimum weight parameters. In addition, we adapt a modified version of the nonlocal means filter as a smoothness prior to utilize the patch redundancy. Experimental results show that the proposed algorithm better restores HR images than existing state-of-the-art methods in the sense of the most objective measures in the literature. PMID- 26831382 TI - Generalized propagation of light through optical systems. II. Numerical implications. AB - We present an algorithm implemented in a MATLAB toolbox that is able to compute the wave propagation of coherent visible light through macroscopic lenses. The mathematical operations that complete the status at the end of the first paper of this sequence, where only limited configurations of the propagation direction were allowed toward arbitrarily directed input beam computations, are provided. With their help, high numerical aperture (NA) field tracing is made possible that is based on fast Fourier routines and is Maxwell exact in the limit of macroscopic structures and large curvature radii, including reflection and transmission. Whereas the curvature-dependent terms in the Helmholtz equation are under analytical control through the first perturbation order in the curvature, they are only included in the propagation distance in the current investigation for the sake of reasonable time consumption. We give a number of examples that demonstrate the strengths of our approach, describe essential differences from other approaches that were not obvious when Paper 1 was written, and list a number of drawbacks and possible simplifications to overcome them. PMID- 26831384 TI - Long-wave infrared polarimetric cluster-based vehicle detection. AB - The sensory perception of other vehicles in cluttered environments is an essential component of situational awareness for a mobile vehicle. However, vehicle detection is normally applied to visible imagery sequences, while in this paper we investigate how polarized, infrared imagery can add additional discriminatory power. Using knowledge about the properties of the objects of interest and the scene environment, we have developed a polarimetric cluster based descriptor to detect vehicles using long-wave infrared radiation in the range of 8-12 MUm. Our approach outperforms both intensity and polarimetric image histogram descriptors applied to the infrared data. For example, at a false positive rate of 0.01 per detection window, our cluster approach results in a true positive rate of 0.63 compared to a rate of 0.05 for a histogram of gradient descriptor trained and tested on the same dataset. In conclusion, we discuss the potential of this new approach in comparison with state-of-the-art infrared and conventional video detection. PMID- 26831383 TI - Fourier phase in Fourier-domain optical coherence tomography. AB - Phase of an electromagnetic wave propagating through a sample-of-interest is well understood in the context of quantitative phase imaging in transmission-mode microscopy. In the past decade, Fourier-domain optical coherence tomography has been used to extend quantitative phase imaging to the reflection-mode. Unlike transmission-mode electromagnetic phase, however, the origin and characteristics of reflection-mode Fourier phase are poorly understood, especially in samples with a slowly varying refractive index. In this paper, the general theory of Fourier phase from first principles is presented, and it is shown that Fourier phase is a joint estimate of subresolution offset and mean spatial frequency of the coherence-gated sample refractive index. It is also shown that both spectral domain phase microscopy and depth-resolved spatial-domain low-coherence quantitative phase microscopy are special cases of this general theory. Analytical expressions are provided for both, and simulations are presented to explain and support the theoretical results. These results are further used to show how Fourier phase allows the estimation of an axial mean spatial frequency profile of the sample, along with depth-resolved characterization of localized optical density change and sample heterogeneity. Finally, a Fourier phase-based explanation of Doppler optical coherence tomography is also provided. PMID- 26831385 TI - Characteristics of guided modes in chiroplasma circular waveguides in magnetized plasma. AB - Theoretical analysis of the electromagnetic wave propagation in circular waveguides with a chiroplasma core and a cladding region filled with an anisotropic plasma medium is presented. The cladding region is assumed to be infinitely extended with an external applied magnetic field oriented along the direction of propagation in the waveguide. The characteristic equation for the modes in this waveguide is obtained. The behavior of the energy flux and the dispersion curves are examined and evaluated computationally. The results demonstrate that the behavior of the energy flux transported in the guide in magnitude and orientation is highly affected by the cyclotron and the plasma frequencies in both regions. The modes' cutoff frequencies are sensitive to the variations in the chirality and the plasma frequency of both regions. PMID- 26831386 TI - On the Bertin surfaces of photoelastic crystals. AB - Conoscopic analysis of interference fringes is one of the most useful tools for investigating the mechanical properties of a crystal. These fringes are generated by a surface of constant phase difference, called the Bertin surface, whose shape depends on the piezo-optic properties of the material and on the applied stress. Here we investigate systematically for the first time, to the best of our knowledge, these surfaces as algebraic surfaces. We also describe their dependence on the stress when these are "small" and give a detailed analysis for all crystallographic classes. PMID- 26831387 TI - Applications of neural networks in human shape visual perception. AB - Advances in optical and electronic technology can immensely reduce noise in images and greatly enhance human visual recognition. However, it is still difficult for human eyes to identify low-resolution thermal images, due to the limits imposed by psychological and physiological factors. In addition, changes in monitor brightness and lens resolution may also interfere with visual recognition abilities. To overcome these limitations, we devised a suitable and effective recognition method which may help the military in revising the shape parameters of long-range targets. The modulation transfer function was used as a basis to extend the visual characteristics of the human visual model and a new model was produced through the incorporation of new shape parameters. The new human visual model was next used in combination with a backpropagation neural network for better recognition of low-resolution thermal images. The new model was then tested in experiments and the results showed that the accuracy rate of recognition steadily rose by over 95%. PMID- 26831388 TI - Coherence and polarization of polarization speckle generated by a rough-surfaced retardation plate depolarizer. AB - The coherence and polarization of polarization speckle, arising from a stochastic electromagnetic field with random change of polarization, modulated by a depolarizer are examined on the basis of the coherence matrix. The depolarizer is a rough-surfaced retardation plate with a random function of position introducing random phase differences between the two orthogonal components of the electric vector. Under the assumption of Gaussian statistics with zero mean, the surface model for the depolarizer of the rough-surfaced retardation plate is obtained. The propagation of the modulated fields through any quadratic optical system is examined within the framework of the complex ABCD matrix theory to show how the degree of coherence and polarization of the beam changes on propagation, including propagation in free space. PMID- 26831389 TI - Adaptive distributed Kalman filtering with wind estimation for astronomical adaptive optics. AB - In the framework of adaptive optics (AO) for astronomy, it is a common assumption to consider the atmospheric turbulent layers as "frozen flows" sliding according to the wind velocity profile. For this reason, having knowledge of such a velocity profile is beneficial in terms of AO control system performance. In this paper we show that it is possible to exploit the phase estimate from a Kalman filter running on an AO system in order to estimate wind velocity. This allows the update of the Kalman filter itself with such knowledge, making it adaptive. We have implemented such an adaptive controller based on the distributed version of the Kalman filter, for a realistic simulation of a multi-conjugate AO system with laser guide stars on a 30 m telescope. Simulation results show that this approach is effective and promising and the additional computational cost with respect to the distributed filter is negligible. Comparisons with a previously published slope detection and ranging wind profiler are made and the impact of turbulence profile quantization is assessed. One of the main findings of the paper is that all flavors of the adaptive distributed Kalman filter are impacted more significantly by turbulence profile quantization than the static minimum mean square estimator which does not incorporate wind profile information. PMID- 26831390 TI - Influence of oblique illumination on perfect Talbot imaging and nearly perfect self-imaging for gratings beyond five diffraction orders. AB - The Talbot self-imaging effect of amplitude gratings is afflicted with aberrations that distort the self-image. This occurs especially if the grating period p is only a few times larger than the illumination wavelength lambda. For example, for lithographic applications of the Talbot effect these aberrations lower the lateral writing resolution and should be minimized. Noponen found, however, some discrete ratios of p/lambda in the interval of 2.0

60 degrees by exactly one third of the angle of refraction. This simple law, plus Snell's law, leads to several analytical results that clarify all aspects of this phenomenon. In particular, it is shown that the intensities of the two symmetrically deflected beams can be equalized by proper choice of the prism refractive index and the azimuth of incident linearly polarized light. ASBS enables a geometrically attractive layout of optical systems that employ multiple prism beam splitters. PMID- 26831399 TI - Introducing JOSA A tutorials: editorial. AB - We describe the new tutorial article type in detail and give some background on the reasons for its introduction. PMID- 26831400 TI - Modulation of IL-1beta reprogrammes the tumor microenvironment to interrupt oral carcinogenesis. AB - Head and neck squamous cell carcinoma (HNSCC) development is a multistage process includes the normal, dysplasia and squamous cell carcinoma (SCC) stages. Recently, increasing evidence has suggested that the tumor microenvironment (TME) is an integral part of malignant transformation. Exploring certain key node genes in TME for future intervention in dysplasia to interrupt oral carcinogenesis was the primary goal of this research. To achieve this goal, systems biology approaches were first applied to the epithelia and fibroblasts collected at sequential stages in a 4-nitroquinoline-1-oxide (4NQO) -induced rat oral carcinogenesis model. Through bioinformatics network construction, IL-1beta was identified as one of the key node genes in TME during carcinogenesis. Immunohistochemical staining of human and rat samples demonstrated that IL-1beta expression patterns were parallel to the stages of malignant transformation. Silencing IL-1beta with lentivirus-delivered shRNA significantly inhibited oral squamous cell carcinoma cell growth both in vivo and in vitro. Based on these findings, we hypothesized that IL-1beta may be a chemoprevention target in TME during oral carcinogenesis. Therefore, we targeted IL-1 in the TME by oral mucosal injection of an IL-1 receptor antagonist in 4NQO rats. The results demonstrated that targeting IL-1 could interrupt oral carcinogenesis by reprogramming the TME. PMID- 26831401 TI - Fundamentals of lateral and vertical heterojunctions of atomically thin materials. AB - At the turn of this century, Herbert Kroemer, the 2000 Nobel Prize winner in Physics, famously commented that "the interface is the device". This statement has since opened up unparalleled opportunities at the interface of conventional three-dimensional (3D) materials (H. Kroemer, Quasi-Electric and Quasi-Magnetic Fields in Non-Uniform Semiconductors, RCA Rev., 1957, 18, 332-342). More than a decade later, Sir Andre Geim and Irina Grigorieva presented their views on 2D heterojunctions which further cultivated broad interests in the 2D materials field. Currently, advances in two-dimensional (2D) materials enable us to deposit layered materials that are only one or few unit-cells in thickness to construct sharp in-plane and out-of-plane interfaces between dissimilar materials, and to be able to fabricate novel devices using these cutting-edge techniques. The interface alone, which traditionally dominated overall device performance, thus has now become the device itself. Fueled by recent progress in atomically thin materials, we are now at the ultimate limit of interface physics, which brings to us new and exciting opportunities, with equally demanding challenges. This paper endeavors to provide stalwarts and newcomers a perspective on recent advances in synthesis, fundamentals, applications, and future prospects of a large variety of heterojunctions of atomically thin materials. PMID- 26831402 TI - On Sample Size and Power Calculation for Variant Set-Based Association Tests. AB - Sample size and power calculations are an important part of designing new sequence-based association studies. The recently developed SEQPower and SPS programs adopted computationally intensive Monte Carlo simulations to empirically estimate power for a series of variant set association (VSA) test methods including the sequence kernel association test (SKAT). It is desirable to develop methods that can quickly and accurately compute power without intensive Monte Carlo simulations. We will show that the computed power for SKAT based on the existing analytical approach could be inflated especially for small significance levels, which are often of primary interest for large-scale whole genome and exome sequencing projects. We propose a new chi(2) -approximation-based approach to accurately and efficiently compute sample size and power. In addition, we propose and implement a more accurate "exact" method to compute power, which is more efficient than the Monte Carlo approach though generally involves more computations than the chi(2) approximation method. The exact approach could produce very accurate results and be used to verify alternative approximation approaches. We implement the proposed methods in publicly available R programs that can be readily adapted when planning sequencing projects. PMID- 26831403 TI - Effect of adiponectin-encoding gene ADIPOQ single nucleotide polymorphisms +45 and +276 on serum lipid levels after antiretroviral therapy in Japanese patients with HIV-1-infection. AB - OBJECTIVES: To investigate the association between single nucleotide polymorphisms (SNPs) in the adiponectin-encoding gene ADIPOQ and changes in serum lipid levels in HIV-1-infected patients after antiretroviral therapy (ART). METHODS: ART-naive HIV-1-infected patients were recruited to this prospective analysis. SNP +45 and SNP +276 genotype was determined by direct sequencing. Multivariate linear regression analysis was performed to analyse the effects of genotype, and predisposing conditions on serum total cholesterol and triglyceride in the 4 months before and after ART initiation. RESULTS: The study enrolled 78 patients with HIV-1-infection (73 male, five female; age range 22-67 years). HIV 1 viral load >=5 log10 copies/ml, baseline total cholesterol >=160 mg/dl, and CD4(+) lymphocyte count <200/ul were associated with increased serum total cholesterol levels after ART initiation. Protease inhibitor treatment and body mass index >=25 kg/m(2) were associated with increased triglyceride levels after ART initiation. There were no significant associations between SNP +45 or SNP +276 genotype and serum total cholesterol or triglyceride levels. CONCLUSIONS: SNP +45 and SNP +276 genotype is not associated with changes in serum total cholesterol or triglyceride levels after ART initiation. PMID- 26831406 TI - Comparative studies on the room-temperature ferrielectric and ferrimagnetic Ni3TeO6-type A2FeMoO6 compounds (A = Sc, Lu). AB - First-principles calculations have been carried out to study the structural, electric, and magnetic properties of Ni3TeO6-type A2FeMoO6 compounds (A = Sc, Lu). Their electric and magnetic properties behave like room-temperature ferrielectric and ferrimagnetic insulators where polarization comes from the un cancelled antiparallel dipoles of (A(1), Fe(3+)) and (A(2), Mo(3+)) ion groups, and magnetization from un-cancelled antiparallel moments of Fe(3+) (d(5)) and Mo(3+) (d(3)) ions. The net polarization increases with A's ionic radius and is 7.1 and 8.7 MUCcm(-2) for Sc2FeMoO6 and Lu2FeMoO6, respectively. The net magnetic moment is 2 MUB per formula unit. The magnetic transition temperature is estimated well above room-temperature due to the strong antiferromagnetic superexchange coupling among Fe(3+) and Mo(3+) spins. The estimated paraelectric to ferrielectric transition temperature is also well above room-temperature. Moreover, strong magnetoelectric coupling is also anticipated because the magnetic ions are involved both in polarization and magnetization. The fully relaxed Ni3TeO6-type A2FeMoO6 structures are free from soft-phonon modes and correspond to stable structures. As a result, Ni3TeO6-type A2FeMoO6 compounds are possible candidates for room-temperature multiferroics with large magnetization and polarization. PMID- 26831405 TI - Protein microarray-mediated detection of antienterovirus antibodies in serum. AB - OBJECTIVE: To utilize prokaryotic gene expression and protein microarray to develop and evaluate a sensitive, accurate protein microarray assay for detecting antienterovirus antibodies in serum samples from patients with hand, foot and mouth disease (HFMD). Enterovirus 71 (EV71) and coxsackievirus A16 (CA16), two common causative agents for HFMD, were used for assay development. METHODS: Serum was collected from patients with HFMD and healthy controls. EV71 and CA16 VP1 and VP3 genes were expressed in transfected Escherichia coli; the resultant VP1 and 3 proteins were used in a microarray assay for human serum EV71 and CA16 immunoglobulin (Ig) M and IgG. To validate the microarray assay, serum samples were tested for EV71 IgM using enzyme-linked immunosorbent assay (ELISA). RESULTS: Out of 50 patients with HFMD, EV71 IgM and CA16 IgM was detected in 80% and 44% of serum samples, respectively, using protein microarray, and EV71 IgM was detected in 78% of samples using ELISA. Protein microarray and ELISA showed 100% specificity for EV71-IgM detection. CONCLUSION: The protein microarray assay developed in the present study shows potential as a sensitive technique for detecting EV71 IgM in serum samples from patients with HFMD. PMID- 26831407 TI - Is Heading in Youth Soccer Dangerous Play? AB - BACKGROUND: Soccer is among the most popular youth sports with over 3 million youth players registered in the U.S. Soccer is unique in that players intentionally use their head to strike the ball, leading to concerns that heading could cause acute or chronic brain injury, especially in the immature brains of children. METHODS: Pub Med search without date restriction was conducted in November 2014 and August 2015 using the terms soccer and concussion, heading and concussion, and youth soccer and concussion. 310 articles were identified and reviewed for applicable content specifically relating to youth athletes, heading, and/or acute or chronic brain injury from soccer. RESULTS: Soccer is a low-risk sport for catastrophic head injury, but concussions are relatively common and heading often plays a role. At all levels of play, concussions are more likely to occur in the act of heading than with other facets of the game. While concussion from heading the ball without other contact to the head appears rare in adult players, some data suggests children are more susceptible to concussion from heading primarily in game situations. Contributing factors include biomechanical forces, less developed technique, and the immature brain's susceptibility to injury. CONCLUSIONS: There is no evidence that heading in youth soccer causes any permanent brain injury and there is limited evidence that heading in youth soccer can cause concussion. A reasonable approach based on U.S. Youth Soccer recommendations is to teach heading after age 10 in controlled settings, and heading in games should be delayed until skill acquisition and physical maturity allow the youth player to head correctly with confidence. PMID- 26831404 TI - Clinical efficacy of neoadjuvant chemotherapy with irinotecan (CPT-11) and nedaplatin followed by radical hysterectomy for locally advanced cervical cancer. AB - OBJECTIVE: To investigate the clinical efficacy of neoadjuvant chemotherapy (NAC) with irinotecan (CPT-11) and nedaplatin (NED) followed by radical hysterectomy. METHODS: Patients with locally advanced cervical cancer (stage Ib2-IIb) were treated with NAC followed by surgery, primary surgery or primary radiotherapy. NAC was usually performed using transuterine arterial chemotherapy (TUAC) or intravenous CPT-11/NED. Survival rates were analysed in the three treatment groups; response rates and adverse events associated with NAC, TUAC and CPT 11/NED were compared, along with previously reported adverse events of chemoradiotherapy. RESULTS: A total of 165 patients with cervical cancer were recruited. Of these, 70 were treated with NAC followed by surgery (48 with CPT 11/NED, 18 with TUAC and four with other types of chemotherapy), 73 were treated with primary surgery and 22 with primary radiotherapy (including chemoradiotherapy). There were no significant differences in progression-free survival or overall survival rates between the three treatment groups. The response rates for the NAC regimen of CPT-11/NED and TUAC were high (75% and 78%, respectively). The frequency of severe thrombocytopenia was lower in patients receiving CPT-11/NED compared with TUAC, and the incidence of severe anaemia, vomiting and cystitis was lower in patients receiving CPT-11/NED compared with chemoradiotherapy. CONCLUSIONS: The use of CPT-11/NED as a NAC regimen shows favourable activity, with lower toxicity compared with NAC using TUAC or chemoradiotherapy, for the treatment of locally advanced cervical cancer. PMID- 26831409 TI - HIV prevention & treatment--reasons to rejoice & remain vigilant. PMID- 26831408 TI - The Prognostic Value of Alpha-Fetoprotein Response for Advanced-Stage Hepatocellular Carcinoma Treated with Sorafenib Combined with Transarterial Chemoembolization. AB - This retrospective cohort study aimed to evaluate the prognostic value of the alpha-fetoprotein (AFP) response in advanced-stage hepatocellular carcinoma (HCC) patients treated with sorafenib combined with transarterial chemoembolization. From May 2008 to July 2012, 118 HCC patients with baseline AFP levels >20 ng/ml treated with combination therapy were enrolled. A receiver operating characteristic curve was used to generate a cutoff point for AFP changes for predicting survival. The AFP response was defined as an AFP decrease rate [DeltaAFP(%)] greater than the cutoff point. The DeltaAFP(%) was defined as the percentage of changes between the baseline and the nadir values within 2 months after therapy. The median follow-up time was 8.8 months (range 1.2-66.9). A level of 46% was chosen as the threshold value for DeltaAFP (sensitivity = 53.7%, specificity = 83.3%). The median overall survival was significantly longer in the AFP response group than in the AFP non-response group (12.8 vs. 6.4 months, P = 0.001). Multivariate analysis showed that ECOG >= 1 (HR = 1.95; 95% CI 1.24-3.1, P = 0.004) and AFP nonresponse (HR = 1.71; 95% CI 1.15-2.55, P = 0.009) were associated with increased risk of death. In conclusion, AFP response could predict the survival of patients with advanced-stage HCC at an early time point after combination therapy. PMID- 26831410 TI - Development & licensing of first ever vaccine against malaria. PMID- 26831411 TI - Genetic basis of asthma. PMID- 26831412 TI - A new era of diagnostic modalities for type 1 leprosy reactions: Promise for the future. PMID- 26831413 TI - Multiple sclerosis--new treatment modalities. AB - Ever since the introduction of the first disease modifying therapies, the concept of multiple sclerosis treatment algorithms developed ceaselessly. The increasing number of available drugs is paralleled by impelling issue of ensuring the most appropriate treatment to the right patient at the right time. The purpose of this review is to describe novel agents recently approved for multiple sclerosis treatment, namely teriflunomide, alemtuzumab and dimethylfumarate, focusing on mechanism of action, efficacy data in experimental setting, safety and tolerability. The place in therapy of newer treatment implies careful balancing of risk-benefit profile as well as accurate patient selection. Hence the widening of therapeutic arsenal provides greater opportunity for personalized therapy but also entails a complex trade-off between efficacy, tolerability, safety and eventually patient preference. PMID- 26831414 TI - Delirium in the elderly: Current problems with increasing geriatric age. AB - Delirium is an acute disorder of attention and cognition seen relatively commonly in people aged 65 yr or older. The prevalence is estimated to be between 11 and 42 per cent for elderly patients on medical wards. The prevalence is also high in nursing homes and long term care (LTC) facilities. The consequences of delirium could be significant such as an increase in mortality in the hospital, long-term cognitive decline, loss of autonomy and increased risk to be institutionalized. Despite being a common condition, it remains under-recognised, poorly understood and not adequately managed. Advanced age and dementia are the most important risk factors. Pain, dehydration, infections, stroke and metabolic disturbances, and surgery are the most common triggering factors. Delirium is preventable in a large proportion of cases and therefore, it is also important from a public health perspective for interventions to reduce further complications and the substantial costs associated with these. Since the aetiology is, in most cases, multifactorial, it is important to consider a multi-component approach to management, both pharmacological and non-pharmacological. Detection and treatment of triggering causes must have high priority in case of delirium. The aim of this review is to highlight the importance of delirium in the elderly population, given the increasing numbers of ageing people as well as increasing geriatric age. PMID- 26831415 TI - Individualization of antiretroviral therapy--pharmacogenomic aspect. AB - Combination therapy with three drug regimens for human immunodeficiency virus (HIV) infection significantly suppresses the viral replication. However, this therapeutic impact is restricted by adverse drug events and response in terms of short and long term efficacy. There are multiple factors involved in different responses to antiretrovirals (ARVs) such as age, body weight, disease status, diet and heredity. Pharmacogenomics deals with individual genetic make-up and its role in drug efficacy and toxicity. In depth genetic research has provided evidence to predict the risk of developing certain toxicities for which personalized screening and surveillance protocols may be developed to prevent side effects. Here we describe the use of pharmacogenomics for optimal use of HAART (highly active antiretroviral therapy). PMID- 26831416 TI - A preliminary study on the association of single nucleotide polymorphisms of interleukin 4 (IL4), IL13, IL4 receptor alpha (IL4Ralpha) & Toll-like receptor 4 (TLR4) genes with asthma in Indian adults. AB - BACKGROUND & OBJECTIVES: Interleukin 4 (IL4) and IL13 genes are believed to be responsible for inflammation of the airways in asthmatics. These share a common receptor component called IL4Ralpha which is another potentially important candidate gene linked to asthma phenotypes. Another gene Toll-like receptor 4 (TLR4) might affect the incidence or progression of asthma through the expression of proinflammatory genes. Several single nucleotide polymorphisms (SNPs) in IL4, IL13, IL4Ralpha and TLR4 have been reported to be linked to asthma or related phenotypes in several ethnic populations using linkage studies and association studies. However, the results have not been consistent. We investigated five SNPs (C-589T and C-33T of IL4, G+2044A of IL13, A+1902G of IL4Ralpha, and A+896G of TLR4) in patients with adult onset asthma to evaluate their role in manifestation and severity of asthma. METHODS: Adult (>18 yr of age) patients with asthma (n=100) and healthy controls (n=50) were included in the study. Genotyping was performed using sequenom MassARRAY technology. RESULTS: The mutant alleles of the C-589T and C-33T SNPs in the promoter region of IL4 were present in 4 per cent patients with asthma but absent from the control group suggesting that the variations in IL4 may contribute to asthma occurrence. The SNPs of other genes were seen in both controls and patients. INTERPRETATION & CONCLUSIONS: The results suggest the possible association between the genetic distribution of C 589T and C-33T SNPs of IL4 with asthma in Indian adults. PMID- 26831417 TI - Is CXCL10/CXCR3 axis overexpression a better indicator of leprosy type 1 reaction than inducible nitric oxide synthase? AB - BACKGROUND & OBJECTIVES: Leprosy type 1 reactions (T1R) are acute episodes of immune exacerbation that are a major cause of inflammation and nerve damage. T1R are diagnosed clinically and supported by histopathology. No laboratory marker is currently available that can accurately predict a T1R. Increased plasma and tissue expression of inducible nitric oxide synthase (i-NOS) and chemokine CXCL10 have been demonstrated in T1R. We studied the gene expression and immunoexpression of i-NOS, CXCL10 and its receptor CXCR3 in clinically and histopathologically confirmed patients with T1R and compared with non-reactional leprosy patients to understand which biomarker has better potential in distinguishing reaction from non-reaction. METHODS: Gene expression of i-NOS, CXCL10 and CXCR3 was studied in 30 skin biopsies obtained from patients with borderline tuberculoid (BT), mid-borderline (BB) and borderline lepromatous (BL) leprosy with and without T1R by real-time PCR. Further validation was done by immunohistochemical expression on 60 borderline leprosy biopsies with and without T1R. RESULTS: Of the 120 patients histopathological evaluation confirmed T1R in 65 (54.2%) patients. CXCR3 gene expression was significantly (P<0.05) higher in BT- and BB-T1R patients compared to those without T1R. The CXCL10 gene expression was significantly higher (P<0.05) in BB leprosy with T1R but the difference was not significant in patients with BT with or without T1R. Immunoexpression for CXCR3 was significant in both BB-T1R and BB (P<0.001) and BT and BT-T1R (P<0.001). Immunoexpression of CXL10 was significant only in differentiating BB from BB-T1R leprosy (P<0.01) and not the BT cases. i-NOS immunoexpression was not useful in differentiating reactional from non-reactional leprosy. INTERPRETATION & CONCLUSIONS: Both CXCL10 and CXCR3 appeared to be useful in differentiating T1R reaction in borderline leprosy while CXCR3 alone differentiated BT from BT-T1R. CXCR3 may be a potentially useful immunohistochemical marker to predict an impending T1R. PMID- 26831418 TI - Association between anthropometry, cardiometabolic risk factors, & early life factors & adult measures of endothelial function: Results from the New Delhi Birth Cohort. AB - BACKGROUND & OBJECTIVES: Abnormal endothelial function represents a preclinical marker of atherosclerosis. This study was conducted to evaluate associations between anthropometry, cardiometabolic risk factors, and early life factors and adult measures of endothelial function in a young urban Indian cohort free of clinical cardiovascular disease. METHODS: Absolute changes in brachial artery diameter following cuff inflation and sublingual nitroglycerin (400 ug) were recorded to evaluate endothelium-dependent and -independent measures of endothelial function in 600 participants (362 men; 238 women) from the New Delhi Birth Cohort (2006-2009). Data on anthropometry, cardiometabolic risk factors, medical history, socio-economic position, and lifestyle habits were collected. Height and weight were recorded at birth, two and 11 yr of age. Age- and sex adjusted linear regression models were developed to evaluate these associations. RESULTS: The mean age of participants was 36+/-1 yr. Twenty two per cent men and 29 per cent women were obese (BMI th > 30 kg/m [2] ). Mean systolic blood pressure (SBP) was 131+/-14 and 119+/-13 mmHg, and diabetes prevalence was 12 and 8 per cent for men and women, respectively. Brachial artery diameter was higher for men compared with women both before (3.48+/-0.37 and 2.95+/-0.35 cm) and after hyperaemia (3.87+/-0.37 vs. 3.37+/-0.35 cm). A similar difference was seen before and after nitroglycerin. Markers of increased adiposity, smoking, SBP, and metabolic syndrome, but not early life anthropometry, were inversely associated with endothelial function after adjustment for age and sex. INTERPRETATION & CONCLUSIONS: The analysis of the current prospective data from a young urban Indian cohort showed that cardiometabolic risk factors, but not early life anthropometry, were associated with worse endothelial function. PMID- 26831419 TI - Recurrent benign copy number variants & issues in interpretation of variants of unknown significance identified by cytogenetic microarray in Indian patients with intellectual disability. AB - BACKGROUND & OBJECTIVES: Cytogenetic microarray (CMA) is now recommended as a first-tier clinical diagnostic test in cases with idiopathic intellectual disability and/or developmental delay (ID/DD). Along with clinically relevant variants, CMA platforms also identify variants of unknown significance (VUS). This study was done to look for utility and various issues in interpretation of copy number variants (CNVs) in Indian patients with ID/DD. METHODS: The CMA was performed in 86 Indian patients with idiopathic ID/DD with or without dysmorphic features. CNV was reported if copy number gain was >400 kb in size and copy number loss was > 200 kb in size. RESULTS: Pathogenic CNVs were found in 18 of 86 (20.9%) patients. One large (14 Mb size) de novo heterozygous copy number gain was found in one patient. VUS (total 31) were present in 17 of 86 (19.7%) patients. Five novel recurrent benign CNVs were also present in our patients. INTERPRETATION & CONCLUSIONS: Our findings highlight the difficulties in interpretation of CNVs identified by CMA. More Indian data on VUS and recurrent benign CNVs will be helpful in the interpretation of CMA in patients with ID/DD. PMID- 26831420 TI - Postural sway in diabetic peripheral neuropathy among Indian elderly. AB - BACKGROUND & OBJECTIVES: Diabetic peripheral neuropathy (DPN) is a major complication of type 2 diabetes and have long term complications on the postural control of the affected population. The objectives of this study were to evaluate postural stability in patients with DPN and to examine correlation of Michigan Neuropathy Screening Instrument (MNSI) with duration of diabetes, age and postural stability measures. METHODS: Participants were included if they had clinical neuropathy which was defined by MNSI. Sixty one patients gave their consent to participate in the study and were evaluated on posturography for postural stability measures in four conditions. Repeated measures of analysis of variance (RANOVA) was used to analyze the changes in postural stability measures in different conditions. RESULTS: An increase in mean value of postural stability measures was observed for velocity moment 20.4+/-1.3, 24.3+/-2.2, 42.3+/-20.7, 59+/-43.03, mediolateral displacement 0.21+/-0.10, 0.22+/-0.18, 0.03+/-0.11, 0.34+/-0.18, and anteroposterior displacement 0.39 +/- 0.09, 0.45+/-0.12, 0.47+/ 0.13, 0.51+/-0.20 from EO to EC, EOF, and ECF, respectively. There was a significant difference (P<0.05) in participants with DPN, with greater sway amplitude on firm and foam surface in all the conditions. Moderate correlation of MNSI with age (r=0.43) and postural stability measures were also observed. INTERPRETATION & CONCLUSIONS: Evaluation of postural stability in Indian DPN population suggests balance impairments on either firm and foam surfaces, with greater likelihood of fall being on foam or deformable surfaces among elderly adults with neuropathy (CTRI/2011/07/001884). PMID- 26831421 TI - Estimation of radiation dose to patients from (18) FDG whole body PET/CT investigations using dynamic PET scan protocol. AB - BACKGROUND & OBJECTIVES: There is a growing concern over the radiation exposure of patients from undergoing 18FDG PET/CT (18F-fluorodeoxyglucose positron emission tomography/computed tomography) whole body investigations. The aim of the present study was to study the kinetics of 18FDG distributions and estimate the radiation dose received by patients undergoing 18FDG whole body PET/CT investigations. METHODS: Dynamic PET scans in different regions of the body were performed in 49 patients so as to measure percentage uptake of 18FDG in brain, liver, spleen, adrenals, kidneys and stomach. The residence time in these organs was calculated and radiation dose was estimated using OLINDA software. The radiation dose from the CT component was computed using the software CT-Expo and measured using computed tomography dose index (CTDI) phantom and ionization chamber. As per the clinical protocol, the patients were refrained from eating and drinking for a minimum period of 4 h prior to the study. RESULTS: The estimated residence time in males was 0.196 h (brain), 0.09 h (liver), 0.007 h (spleen), 0.0006 h (adrenals), 0.013 h (kidneys) and 0.005 h (stomach) whereas it was 0.189 h (brain), 0.11 h (liver), 0.01 h (spleen), 0.0007 h (adrenals), 0.02 h (kidneys) and 0.004 h (stomach) in females. The effective dose was found to be 0.020 mSv/MBq in males and 0.025 mSv/MBq in females from internally administered 18FDG and 6.8 mSv in males and 7.9 mSv in females from the CT component. For an administered activity of 370 MBq of 18FDG, the effective dose from PET/CT investigations was estimated to be 14.2 mSv in males and 17.2 mSv in females. INTERPRETATION & CONCLUSIONS: The present results did not demonstrate significant difference in the kinetics of 18FDG distribution in male and female patients. The estimated PET/CT doses were found to be higher than many other conventional diagnostic radiology examinations suggesting that all efforts should be made to clinically justify and carefully weigh the risk-benefit ratios prior to every 18FDG whole body PET/CT scan. PMID- 26831422 TI - Constitutive expression of SMAR1 confers susceptibility to Mycobacterium tuberculosis infection in a transgenic mouse model. AB - BACKGROUND & OBJECTIVES: Studies involving animal models of experimental tuberculosis have elucidated the predominant role of cytokines secreted by T cells and macrophages to be an essential component of the immune response against Mycobacterium tuberculosis infection. The immune activities of CD4+ T cells are mediated in part by Th1 cytokine interferon gamma (IFN-gamma) which is produced primarily by T cells and natural killer (NK) cells and critical for initiating the immune response against intracellular pathogen such as M. tuberculosis. Nuclear matrix protein SMAR1 plays an important role in V(D)J recombination, T helper cell differentiation and inflammatory diseases. In this study a transgenic mouse model was used to study the role of SMAR1 in M. tuberculosis infection. METHODS: Wild type BALB/c, C57BL/6, BALB/c-EGFP-SMAR1 and C57BL/6-SMAR1 transgenic mice were infected with M. tuberculosis (H37Rv). A dose of 100 bacilli was used for infection via respiratory route. Bacterial load in lung and spleen of infected mice was determined at 2, 4, 6 and 8 wk post-infection. Gene expression analysis for Th1 cytokines and inducible nitric oxide synthase (iNOS) was performed in infected lung tissues by quantitative reverse transcription (RT) PCR. RESULTS: SMAR1 transgenic mice from both BALB/c and C57BL/6 genetic background displayed higher bacillary load and susceptibility to M. tuberculosis infection compared to wild type mice. This susceptibility was attributed due to compromised of Th1 response exhibited by transgenic mice. INTERPRETATION & CONCLUSIONS: SMAR1 transgenic mice exhibited susceptibility to M. tuberculosis infection in vivo irrespective of genetic background. This susceptibility was attributed to downregulation of Th1 response and its hallmark cytokine IFN-gamma. Hence, SMAR1 plays an important role in modulating host immune response after M. tuberculosis infection. PMID- 26831423 TI - Comparing the effects of Bentonite & Calendula on the improvement of infantile diaper dermatitis: A randomized controlled trial. AB - BACKGROUND & OBJECTIVES: Infantile diaper dermatitis is a common, acute inflammatory reaction of the skin around diaper among infants. This study was undertaken to compare the effect of topical application of Bentonite and Calendula creams on the improvement of infantile diaper dermatitis. METHODS: This double blind randomized controlled trial was undertaken on 100 patients of infantile diaper dermatitis. The 100 participants were randomly assigned into two groups of 50 each, and were prescribed the coded medicine. The mothers were trained to apply the cream and level of improvement was judged by observing the affected area on the first visit and then after three days of receiving treatment. RESULTS: The mean age of infants was 6.45+/-5.53 months in Calendula group and 7.35+/-6.28 months in Bentonite group. Overall, 88 per cent of lesions in the Bentonite group started improving in the first six hours while this rate was 54 per cent in Calendula group (P<0.001). The risk ratio for the improvement in the first six hours was 2.99 folds in the Bentonite group. Also, lesions in 86 per cent infants in the Bentonite group and 52 per cent in the Calendula group were completely improved in the first three days after treatment (P<0.001). INTERPRETATION & CONCLUSIONS: Our results showed that in comparison with Calendula, Bentonite had faster healing effect and was more effective on the improvement of infantile diaper dermatitis (IRCT ID: IRCT 2012112811593N1). PMID- 26831424 TI - Culture & differentiation of mesenchymal stem cell into osteoblast on degradable biomedical composite scaffold: In vitro study. AB - BACKGROUND & OBJECTIVES: There is a significant bone tissue loss in patients from diseases and traumatic injury. The current autograft transplantation gold standard treatment has drawbacks, namely donor site morbidity and limited supply. The field of tissue engineering has emerged with a goal to provide alternative sources for transplantations to bridge this gap between the need and lack of bone graft. The aim of this study was to prepare biocomposite scaffolds based on chitosan (CHT), polycaprolactone (PCL) and hydroxyapatite (HAP) by freeze drying method and to assess the role of scaffolds in spatial organization, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro, in order to achieve bone graft substitutes with improved physical-chemical and biological properties. METHODS: Pure chitosan (100CHT) and composites (40CHT/HAP, 30CHT/HAP/PCL and 25CHT/HAP/PCL scaffolds containing 40, 30, 25 parts per hundred resin (phr) filler, respectively) in acetic acid were freeze dried and the porous foams were studied for physicochemical and in vitro biological properties. RESULTS: Scanning electron microscope (SEM) images of the scaffolds showed porous microstructure (20-300 MUm) with uniform pore distribution in all compositions. Materials were tested under compressive load in wet condition (using phosphate buffered saline at pH 7.4). The in vitro studies showed that all the scaffold compositions supported mesenchymal stem cell attachment, proliferation and differentiation as visible from SEM images, [3-(4,5 dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay, alkaline phosphatase (ALP) assay and quantitative reverse transcription (qRT)-PCR. INTERPRETATION & CONCLUSIONS: Scaffold composition 25CHT/HAP/PCL showed better biomechanical and osteoinductive properties as evident by mechanical test and alkaline phosphatase activity and osteoblast specific gene expression studies. This study suggests that this novel degradable 3D composite may have great potential to be used as scaffold in bone tissue engineering. PMID- 26831425 TI - Additional markers for genetic diagnosis of type 3 von Willebrand disease in Indian population. PMID- 26831426 TI - Adrenal reserve in acute exacerbation of non-cystic fibrosis bronchiectasis. PMID- 26831427 TI - Selection bias: Selection of controls as a critical issue in the interpretation of results in a case control study. PMID- 26831428 TI - Authors' response. PMID- 26831429 TI - The fifth cardiac chamber: Case of a huge left atrial appendage aneurysm. PMID- 26831430 TI - Synovial chondromatosis of knee. PMID- 26831431 TI - Kimura disease: A rare case of bilateral infra-auricular masses. PMID- 26831432 TI - The anthelmintic effects of the ethanol extract of Terminalia catappa L. leaves against the ruminant gut parasite, Fischoederius cobboldi. AB - Presently, no effective anthelmintic drugs have been used to treat and control paramphistomosis, a severe disease of ruminants. In this study, we have investigated the in vitro anthelmintic effect of the leaves of Terminalia catappa L. crude extract (TcCE) and albendazole (ABZ) on adult Fischoederius cobboldi after incubating the flukes in RPMI-1640 medium containing the TcCE at various doses and times. The TcCE-treated flukes at all dosages exhibited rapid decrease of motility, and the relative motility (RM) values were decreased sharply from start to 3 h. Worms were killed after 6 and 12 h of treatment with 1000, 1500 and 2000 ug mL(-1) as well as 500 ug mL(-1) of TcCE, respectively. By light microscopy examination, the flukes exhibited the earliest alteration in a limited area of the tegument. At scanning electron microscopy level, the flukes' tegument showed similar sequence of morphological alterations after treatment with ABZ and TcCE that consisted of swelling of ridges and folds, followed by blebbing and rupturing of the blebs, leading to the erosion, lesion and disruption of the tegument. Hence, in vivo studies should be performed to examine whether the TcCE may serve as a powerful anthelmintic drug for treatment of paramphistomosis. PMID- 26831434 TI - Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease. AB - Patients with chronic kidney disease and end-stage renal disease are at 5- to 10 fold higher risk for developing cardiovascular disease (CVD) than age-matched controls. Clinically, CVD in this population manifests as coronary artery disease, arrhythmias, stroke, or congestive heart failure. Beyond the traditional risk factors (eg, diabetes mellitus and hypertension), uremia-specific factors that arise from accumulating toxins also contribute to the pathogenesis of CVD. In this review, we summarize the literature on the epidemiology of both traditional and uremia-related CVD and focus on postulated mechanisms of the latter. In the context of current and emerging diagnostics and therapies for CVD, we highlight what we interpret as major gaps in the medical management of this growing population that need to be addressed with targeted epidemiological and translational research. Finally, we describe the global challenges associated with the recognition and management of uremia-related CVD in developed and developing nations. PMID- 26831437 TI - Spontaneous Intramural Hematoma of the Left Ventricle. PMID- 26831435 TI - Cardiovascular Effects of Androgen Deprivation Therapy for the Treatment of Prostate Cancer: ABCDE Steps to Reduce Cardiovascular Disease in Patients With Prostate Cancer. PMID- 26831433 TI - Emerging From the Unknown: Structural and Functional Features of Agnoprotein of Polyomaviruses. AB - Agnoprotein is an important regulatory protein of polyomaviruses, including JCV, BKV, and SV40. In the absence of its expression, these viruses are unable to sustain their productive life cycle. It is a highly basic phosphoprotein that localizes mostly to the perinuclear area of infected cells, although a small amount of the protein is also found in nucleus. Much has been learned about the structure and function of this important regulatory protein in recent years. It forms highly stable dimers/oligomers in vitro and in vivo through its Leu/Ile/Phe rich domain. Structural NMR studies revealed that this domain adopts an alpha helix conformation and plays a critical role in the stability of the protein. It associates with cellular proteins, including YB-1, p53, Ku70, FEZ1, HP1alpha, PP2A, AP-3, PCNA, and alpha-SNAP; and viral proteins, including small t antigen, large T antigen, HIV-1 Tat, and JCV VP1; and significantly contributes the viral transcription and replication. This review summarizes the recent advances in the structural and functional properties of this important regulatory protein. J. Cell. Physiol. 231: 2115-2127, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26831438 TI - Type B Dissection in a Pregnant Woman Managed With Peripartum Thoracic Endovascular Aortic Repair. PMID- 26831439 TI - Letter by Lippi and Cervellin Regarding Article, "Optimal Cutoff Levels of More Sensitive Cardiac Troponin Assays for the Early Diagnosis of Myocardial Infarction in Patients With Renal Dysfunction". PMID- 26831440 TI - Letter by Yang and Xu Regarding Article, "Optimal Cutoff Levels of More Sensitive Cardiac Troponin Assays for the Early Diagnosis of Myocardial Infarction in Patients With Renal Dysfunction". PMID- 26831441 TI - Letter by Wasfy et al Regarding Article, "Facility Level Variation in Hospitalization, Mortality, and Costs in the 30 Days After Percutaneous Coronary Intervention: Insights on Short-Term Healthcare Value From the Veterans Affairs Clinical Assessment, Reporting, and Tracking System (VA CART) Program". PMID- 26831442 TI - Response to Letter Regarding Article, "Facility Level Variation in Hospitalization, Mortality, and Costs in the 30 Days After Percutaneous Coronary Intervention: Insights on Short-Term Healthcare Value From the Veterans Affairs Clinical Assessment, Reporting, and Tracking System (VA CART) Program". PMID- 26831443 TI - Letter by Nadir Regarding Article, "Prevalence, Clinical Features, and Prognosis of Acute Myocardial Infarction Attributable to Coronary Artery Embolism". PMID- 26831444 TI - Response to Letter Regarding Article, "Prevalence, Clinical Features, and Prognosis of Acute Myocardial Infarction Attributable to Coronary Artery Embolism". PMID- 26831445 TI - Cellulose Buccoadhesive Film Bearing Glimepiride: Physicomechanical Characterization and Biophysics of Buccoadhesion. AB - The present study aimed to develop buccoadhesive film of glimepiride with unique combination of polymers and to investigate its effect(s) on physicomechanical parameters, drug-release, and permeation of films. Drug-polymer interaction was examined by FTIR and DSC analysis. Films were prepared by solvent casting technique and characterized for film strength (320 +/- 8.5 g, 28.98 +/- 2.00 mJ), buccoadhesive strength (28.8 +/- 1.37 g, 3.04 +/- 0.32 mJ), and tensile strength (260 +/- 6.88 g, 18.00 +/- 0.44 mJ) by new instrumental techniques. Increase in polymer concentration augmented zeta potential of polymeric matrix-mucin mixture and exhibited strong buccoadhesion (electrical theory). Buccoadhesion was also influenced by particle size (adsorption theory) and swelling (wetting theory). Erosion behavior of films was observed in swelling and SEM studies. Film GM4 exhibited 98 +/- 2% in vitro drug release and 85 +/- 8% ex vivo drug permeation in 12 h with controlled diffusion mechanism. Films were compatible with oral probiotic microorganisms. Stability studies revealed no significant (P < 0.05) variation in physicomechanical characteristics. PMID- 26831446 TI - Preparation, Pharmacokinetic Profile, and Tissue Distribution Studies of a Liposome-Based Formulation of SN-38 Using an UPLC-MS/MS Method. AB - The application of 7-ethyl-10-hydroxycamptothecin (SN-38) in cancer treatment is limited by its low solubility. This study is to develop a liposome-entrapped formulation of SN-38 (LE-SN38) to solve the obstacle and to evaluate its pharmacokinetic profile in dogs and tissue distribution in mice. LE-SN38 which is more likely to be suitable for large-scale production was prepared by the carrier deposition method. An UPLC-MS/MS method was used to determinate the concentration of SN-38 in this study. LE-SN38 was cleared rapidly from dog plasma within 1 h, and the AUC0-infinity values of three dosages of LE-SN38 indicated an apparent dose-dependent manner. As for the distribution study, the peak of SN-38 levels in most tissues were detected within 10 min after LE-SN38 administration. In addition, concentration of SN-38 in most tissues except kidney and heart in LE SN38 group was higher than that in irinotecan hydrochloride (CPT-11) group generally, whereas the administrated CPT-11 had 20 times dosage compared to LE SN38. LE-SN38 was rapidly eliminated from dog plasma and manifested linear dynamics in dose range of 0.411-1.644 mg/kg. The distribution behavior of SN-38 is altered in a liposome-based delivery system. At the same time, LE-SN38 has lower toxicity compared to CPT-11 in some degree. PMID- 26831447 TI - Development of Molecularly Imprinted Olanzapine Nano-particles: In Vitro Characterization and In Vivo Evaluation. AB - Molecularly imprinted nano-particles (MINPs) selective for olanzapine were prepared using methacrylic acid (MA) as monomer, ethylene glycol dimethacrylate (EGDMA) as a cross-linker, and 2,2-azobis (2-isobutyronitrile) (AIBN) as the initiator in 36 different ratios. The reaction runs with considerable fine powder formation were selected for further binding and selectivity studies. The MINP with the best selectivity (MINP-32) was chosen for further structural characterization by Fourier transform infrared spectroscopy (FT-IR), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), adsorption desorption isotherm for specific surface area, volume and average pore diameter determination. All characterization methods confirmed the successful formation of MINP. The optimum conditions for maximum template loading on the MINP-32 were found by experimental design using response surface methodology (RSM) and choosing absorbent amount, pH, and time as the main factors. MINPs with maximum template loading also indicated significant selectivity between template and its analog (clozapine). The release profile demonstrated a maximum release of about 95% after 288 h for MINP-32 in comparison with about 94% after 120 h for non-MINP 32. The same slow release of drug from MINP-32 was also observed during animal study of the plasma level of template, 20-28 MUg/ml versus 5-10 MUg/ml. The MINP 32 of this study represents a desirable ability to keep the memory of the template with significant selectivity and good capability to control the release of template in vitro and in vivo and hence could be a promising drug delivery system. PMID- 26831448 TI - SLAH3-type anion channel expressed in poplar secretory epithelia operates in calcium kinase CPK-autonomous manner. AB - Extrafloral nectaries secrete a sweet sugar cocktail that lures predator insects for protection from foraging herbivores. Apart from sugars and amino acids, the nectar contains the anions chloride and nitrate. Recent studies with Populus have identified a type of nectary covered by apical bipolar epidermal cells, reminiscent of the secretory brush border epithelium in animals. Border epithelia operate transepithelial anion transport, which is required for membrane potential and/or osmotic adjustment of the secretory cells. In search of anion transporters expressed in extrafloral nectaries, we identified PttSLAH3 (Populus tremula * Populus tremuloides SLAC1 Homologue3), an anion channel of the SLAC/SLAH family. When expressed in Xenopus oocytes, PttSLAH3 displayed the features of a voltage dependent anion channel, permeable to both nitrate and chloride. In contrast to the Arabidopsis SLAC/SLAH family members, the poplar isoform PttSLAH3 is independent of phosphorylation activation by protein kinases. To understand the basis for the autonomous activity of the poplar SLAH3, we generated and expressed chimera between kinase-independent PttSLAH3 and kinase-dependent Arabidopsis AtSLAH3. We identified the N-terminal tail and, to a lesser extent, the C terminal tail as responsible for PttSLAH3 kinase-(in)dependent action. This feature of PttSLAH3 may provide the secretory cell with a channel probably controlling long-term nectar secretion. PMID- 26831449 TI - Small scale green infrastructure design to meet different urban hydrological criteria. AB - As small scale green infrastructures, rain gardens have been widely advocated for urban stormwater management in the contemporary low impact development (LID) era. This paper presents a simple method that consists of hydrological models and the matching plots of nomographs to provide an informative and practical tool for rain garden sizing and hydrological evaluation. The proposed method considers design storms, infiltration rates and the runoff contribution area ratio of the rain garden, allowing users to size a rain garden for a specific site with hydrological reference and predict overflow of the rain garden under different storms. The nomographs provide a visual presentation on the sensitivity of different design parameters. Subsequent application of the proposed method to a case study conducted in a sub-humid region in China showed that, the method accurately predicted the design storms for the existing rain garden, the predicted overflows under large storm events were within 13-50% of the measured volumes. The results suggest that the nomographs approach is a practical tool for quick selection or assessment of design options that incorporate key hydrological parameters of rain gardens or other infiltration type green infrastructure. The graphic approach as displayed by the nomographs allow urban planners to demonstrate the hydrological effect of small scale green infrastructure and gain more support for promoting low impact development. PMID- 26831450 TI - Previously published midazolam-alfentanil response surface model cannot predict patient response well in gastrointestinal endoscopy sedation. AB - BACKGROUND: A response surface model is a mathematical model used to predict multiple-drug pharmacodynamic interactions. With the use of a previously published volunteer model, we tested the accuracy of the midazolam-alfentanil response surface model during gastrointestinal endoscopy. METHODS: We enrolled 35 adult patients scheduled for combined endoscopic procedures. Patients were sedated with intravenous midazolam and alfentanil, and monitored with real-time auditory evoked potential. Sedation Observer's Assessment of Alertness/Sedation (OAA/S) scores were recorded by an independent observer every 2 minutes. Patients with OAA/S scores of >= 4 were designated as "awake". Pharmacokinetic profiles were calculated using the TIVA trainer. The published response surface model was modified to make estimations more reasonable. Patient response (OAA/S score >= 4 or <4) was then estimated using the modified version of the model. RESULTS: The average procedural times were 3.3 +/- 2 minutes and 6.5 +/- 2.3 minutes for esophagogastroduodenoscopy and colonoscopy, respectively. The model poorly predicted patient response during gastrointestinal endoscopic procedure sedation. Accuracy in predicting an OAA/S score of <4 was 6% for the original model and 0% for the modified model. The estimated probability of loss of response ranged from 0.04% to 2.94% at the time of arousal (OAA/S score >= 4) and from 0.24% to 15.55% when the patient was asleep (OAA/S score < 4). CONCLUSION: The model showed significant synergy between midazolam and alfentanil; however, it was inadequate in predicting the response of patients undergoing sedated gastrointestinal endoscopic procedures. Future model parameter adjustments are required. PMID- 26831451 TI - Overview on Peroxiredoxin. AB - Peroxiredoxins (Prxs) are a very large and highly conserved family of peroxidases that reduce peroxides, with a conserved cysteine residue, designated the "peroxidatic" Cys (CP) serving as the site of oxidation by peroxides (Hall et al., 2011; Rhee et al., 2012). Peroxides oxidize the CP-SH to cysteine sulfenic acid (CP-SOH), which then reacts with another cysteine residue, named the "resolving" Cys (CR) to form a disulfide that is subsequently reduced by an appropriate electron donor to complete a catalytic cycle. This overview summarizes the status of studies on Prxs and relates the following 10 minireviews. PMID- 26831452 TI - An Integrative Approach to Precision Cancer Medicine Using Patient-Derived Xenografts. AB - Cancer is a heterogeneous disease caused by diverse genomic alterations in oncogenes and tumor suppressor genes. Despite recent advances in high-throughput sequencing technologies and development of targeted therapies, novel cancer drug development is limited due to the high attrition rate from clinical studies. Patient-derived xenografts (PDX), which are established by the transfer of patient tumors into immunodeficient mice, serve as a platform for co-clinical trials by enabling the integration of clinical data, genomic profiles, and drug responsiveness data to determine precisely targeted therapies. PDX models retain many of the key characteristics of patients' tumors including histology, genomic signature, cellular heterogeneity, and drug responsiveness. These models can also be applied to the development of biomarkers for drug responsiveness and personalized drug selection. This review summarizes our current knowledge of this field, including methodologic aspects, applications in drug development, challenges and limitations, and utilization for precision cancer medicine. PMID- 26831455 TI - Superparamagnetic nanomaterial Fe3O4-TiO2 for the removal of As(V) and As(III) from aqueous solutions. AB - A magnetically separable nanomaterial Fe3O4-TiO2 was synthesized and characterized which was subsequently used for the removal of arsenic (V) from aqueous solutions. The surface morphology, magnetic properties, crystalline structure, thermal stability and Brunauer-Emmet-Teller surface area of the synthesized Fe3O4-TiO2 nanoparticles (NPs) are characterized by scanning electron microscope and high-resolution transmission electron microscope, vibrating sample magnetometry, X-ray diffractometer, thermogravimetric analysis and multi point function surface area analyzer. The saturation magnetization of Fe3O4-TiO2 NPs was determined to be 50.97 emu/g, which makes them superparamagnetic. The surface area of Fe3O4-TiO2 NPs was as much as 94.9 m(2)/g. The main factors affecting adsorption efficiency, such as solution pH, reaction time, initial As(V) concentration and adsorbent concentration are investigated. When the adsorption isotherms were analyzed by the Langmuir, Freundlich and Dubinin-Radushkevich models, equilibrium data were found to be well represented by Freundlich isotherm, and adsorption on Fe3O4-TiO2 NPs fitted well with pseudo-second-order kinetic model. The maximum adsorption capacity of As(V) on Fe3O4-TiO2 NPs, calculated by the Freundlich model was determined at 11.434 ug/g. 1.0 g/L of Fe3O4-TiO2 NPs was efficient for complete removal of 100 ug/L As(V) in 1 h. Fe3O4 TiO2 NPs was also effective for 93% removal of 100 ug/L As(III). Matrix effect was determined using As(V)-contaminated well water. Successfull results were obtained for purification of real well water containing 137.12 ug/L As(V). Results show that Fe3O4-TiO2 NPs are promising adsorbents with an advantage of magnetic separation. PMID- 26831453 TI - Sirt1 and the Mitochondria. AB - Sirt1 is the most prominent and extensively studied member of sirtuins, the family of mammalian class III histone deacetylases heavily implicated in health span and longevity. Although primarily a nuclear protein, Sirt1's deacetylation of Peroxisome proliferator-activated receptor Gamma Coactivator-1alpha (PGC 1alpha) has been extensively implicated in metabolic control and mitochondrial biogenesis, which was proposed to partially underlie Sirt1's role in caloric restriction and impacts on longevity. The notion of Sirt1's regulation of PGC 1alpha activity and its role in mitochondrial biogenesis has, however, been controversial. Interestingly, Sirt1 also appears to be important for the turnover of defective mitochondria by mitophagy. I discuss here evidences for Sirt1's regulation of mitochondrial biogenesis and turnover, in relation to PGC-1alpha deacetylation and various aspects of cellular physiology and disease. PMID- 26831456 TI - Internet addiction: reappraisal of an increasingly inadequate concept. AB - This article re-examines the popular concept of Internet addiction, discusses the key problems associated with it, and proposes possible alternatives. The concept of Internet addiction is inadequate for several reasons. Addiction may be a correct designation only for the minority of individuals who meet the general criteria for addiction, and it needs to be better demarcated from various patterns of excessive or abnormal use. Addiction to the Internet as a medium does not exist, although the Internet as a medium may play an important role in making some behaviors addictive. The Internet can no longer be separated from other potentially overused media, such as text messaging and gaming platforms. Internet addiction is conceptually too heterogeneous because it pertains to a variety of very different behaviors. Internet addiction should be replaced by terms that refer to the specific behaviors (eg, gaming, gambling, or sexual activity), regardless of whether these are performed online or offline. PMID- 26831454 TI - Emerging Roles of RNA-Binding Proteins in Plant Growth, Development, and Stress Responses. AB - Posttranscriptional regulation of RNA metabolism, including RNA processing, intron splicing, editing, RNA export, and decay, is increasingly regarded as an essential step for fine-tuning the regulation of gene expression in eukaryotes. RNA-binding proteins (RBPs) are central regulatory factors controlling posttranscriptional RNA metabolism during plant growth, development, and stress responses. Although functional roles of diverse RBPs in living organisms have been determined during the last decades, our understanding of the functional roles of RBPs in plants is lagging far behind our understanding of those in other organisms, including animals, bacteria, and viruses. However, recent functional analysis of multiple RBP family members involved in plant RNA metabolism and elucidation of the mechanistic roles of RBPs shed light on the cellular roles of diverse RBPs in growth, development, and stress responses of plants. In this review, we will discuss recent studies demonstrating the emerging roles of multiple RBP family members that play essential roles in RNA metabolism during plant growth, development, and stress responses. PMID- 26831461 TI - Alphalpha-2 Adrenergic and Opioids Receptors Participation in Mice Gastroprotection of Abelmoschus esculentus Lectin. AB - Lectins are a heterogeneous group of proteins and glycoproteins with potential role as therapeutic and diagnostic tools to combat various diseases, besides some functions on human organism. Abelmoschus esculentus (Okra), a horticultural plant of African origin, is cultivated in northeastern Brazil, and used for different medicinal purposes. This work is aimed to elucidate the action mechanisms of Abelmoschus esculentus lectin (AEL) gastro protective effect on gastropathy induced by ethanol. Fasted mice treated with Ethanol 99.9% (0.2 ml/animal, p.o.) received previously AEL (0.01, 0.1, 1.0, 10 or 50 mg/kg, i.v.), saline (5 ml/kg; i.v.) or ranitidine (80 mg/kg, p.o.) in four experimental series, in which pharmacological tools (yohimbine, naloxone, L-NAME or indomethacin), were administered with the purpose of make clear possible molecular action mechanisms. Mice were euthanized 30 min after ethanol challenge to verify the stomach damages. Establishment of gastric oxidative stress, tissue hemoglobin (Hb) content and microscopic features (H&E) were taken in order to characterize the AEL gastro protective effect. AEL (1 mg/kg) was capable of protect mucosa against ethanol damages in presence of two (L-NAME and indomethacin) of four antagonists/inhibitors used. The AEL effect was reversed by naloxone and yohimbine, showing the involvement of opioids and Alphalpha-2 adrenergic receptors on gastric protective effect of this lectin. Evaluation of microscopic features, oxidative stress, and Hb levels pointed the protective effects of AEL. This activity seems to be mediated by alpha-2 adrenergic and opioid receptors activation. Nitric oxide or prostaglandins were not involved. AEL simultaneously showed antioxidant effect that is probably implicated in its intricate defensive mechanism of action. PMID- 26831462 TI - Prospects of Developing Medicinal Therapeutic Strategies and Pharmaceutical Design for Effective Gluten Intolerance Treatment. AB - Gluten intolerance is an umbrella term for gluten-related disorders manifested in health decline as a result of the gluten ingestion. The spectrum of gluten related disorders includes three major groups: autoimmune (mainly, Celiac Disease, CD, also known as Celiac Sprue, dermatitis herpetiformis, or gluten sensitive ataxia), allergic (wheat allergy, WA), and non-autoimmune non-allergic (non-celiac gluten sensitivity, NCGS, or gluten sensitivity, GS). Pathogenesis and diagnostics of CD and WA are well established in contrast to NCGS, pathogenicity of which is still poorly understood and its symptoms are frequently misdiagnosed since most of the NCGS cases are currently identified via the process of CD and WA exclusion. By now, the only one proven effective way for CD treatment is gluten-free diet (GFD). However, such an increasingly gaining popularity diet is apparently unsuitable for NCGS treatment because in this case gluten does not always arise as the major or exclusive culprit of gastrointestinal disorder. Furthermore, it is some physicians' opinion that GFD can be deficient in fiber and in other vitamins and minerals. In many cases, GFD is commercially inaccessible for the most needy, whereas strict adherence to the diet is complicated by the presence of small amounts of the gluten components in some foods and even medicines. In this regard, a number of research groups and pharmaceutical companies are extensively developing alternative medicinal approaches to GFD for effective gluten intolerance treatment. This review summarizes our understanding of gluten-related disorders, possible mechanisms of gluten intolerance activation and advantages of gluten intolerance medicinal treatment using novel drug candidates obtained with a proper pharmaceutical design. PMID- 26831463 TI - Allosteric Modulation of Nicotinic Acetylcholine Receptors: The Concept and Therapeutic Trends. AB - Expressing functional nicotinic acetylcholine receptors (nAChRs) may be beneficial to central neurons and neuronal networks because activation of nAChRs enhances neuronal resistance to injury, improves attention, cognitive performance, and produces robust anti-inflammatory and analgesic effects in mammals. Although exogenous orthosteric nAChR ligands present valuable tools in treatment of age- and trauma-related neurological deficits, therapeutic approaches that could amplify the brain's innate ability to maintain cholinergic homeostasis and resist injury may serve as intriguing and promising alternatives and have not been fully explored. One of these novel approaches utilizes positive allosteric modulators (PAMs) of nAChRs. Because of the ubiquitous expression of nAChRs in neuronal, glial and immune tissues, highly selective PAMs could amplify multiple endogenous neuroprotective, pro-cognitive, anti-inflammatory and anti nociceptive cholinergic pathways to offset cholinergic hypofunction and generate therapeutic efficacy by targeting only a single player: i.e., nAChRs activated by endogenous cholinergic tone. In this article, I review the concept of allosteric modulation and current trends in therapeutic applications of nicotinic PAMs. PMID- 26831464 TI - Gene profiling of embryonic skeletal muscle lacking type I ryanodine receptor Ca(2+) release channel. AB - In mature skeletal muscle, the intracellular Ca(2+) concentration rises dramatically upon membrane depolarization, constituting the link between excitation and contraction. This process requires Ca(2+) release from the sarcoplasmic reticulum via the type 1 ryanodine receptor (RYR1). However, RYR1's potential roles in muscle development remain obscure. We used an established RyR1 null mouse model, dyspedic, to investigate the effects of the absence of a functional RYR1 and, consequently, the lack of RyR1-mediated Ca(2+) signaling, during embryogenesis. Homozygous dyspedic mice die after birth and display small limbs and abnormal skeletal muscle organization. Skeletal muscles from front and hind limbs of dyspedic fetuses (day E18.5) were subjected to microarray analyses, revealing 318 differentially expressed genes. We observed altered expression of multiple transcription factors and members of key signaling pathways. Differential regulation was also observed for genes encoding contractile as well as muscle-specific structural proteins. Additional qRT-PCR analysis revealed altered mRNA levels of the canonical muscle regulatory factors Six1, Six4, Pax7, MyoD, MyoG and MRF4 in mutant muscle, which is in line with the severe developmental retardation seen in dyspedic muscle histology analyses. Taken together, these findings suggest an important non-contractile role of RyR1 or RYR1-mediated Ca(2+) signaling during muscle organ development. PMID- 26831465 TI - Pathophysiological Mechanisms in Gaseous Therapies for Severe Malaria. AB - Over 200 million people worldwide suffer from malaria every year, a disease that causes 584,000 deaths annually. In recent years, significant improvements have been achieved on the treatment of severe malaria, with intravenous artesunate proving superior to quinine. However, mortality remains high, at 8% in children and 15% in adults in clinical trials, and even worse in the case of cerebral malaria (18% and 30%, respectively). Moreover, some individuals who do not succumb to severe malaria present long-term cognitive deficits. These observations indicate that strategies focused only on parasite killing fail to prevent neurological complications and deaths associated with severe malaria, possibly because clinical complications are associated in part with a cerebrovascular dysfunction. Consequently, different adjunctive therapies aimed at modulating malaria pathophysiological processes are currently being tested. However, none of these therapies has shown unequivocal evidence in improving patient clinical status. Recently, key studies have shown that gaseous therapies based mainly on nitric oxide (NO), carbon monoxide (CO), and hyperbaric (pressurized) oxygen (HBO) alter vascular endothelium dysfunction and modulate the host immune response to infection. Considering gaseous administration as a promising adjunctive treatment against severe malaria cases, we review here the pathophysiological mechanisms and the immunological aspects of such therapies. PMID- 26831466 TI - Flagellar Cap Protein FliD Mediates Adherence of Atypical Enteropathogenic Escherichia coli to Enterocyte Microvilli. AB - The expression of flagella correlates with different aspects of bacterial pathogenicity, ranging from adherence to host cells to activation of inflammatory responses by the innate immune system. In the present study, we investigated the role of flagella in the adherence of an atypical enteropathogenic Escherichia coli (aEPEC) strain (serotype O51:H40) to human enterocytes. Accordingly, isogenic mutants deficient in flagellin (FliC), the flagellar structural subunit; the flagellar cap protein (FliD); or the MotAB proteins, involved in the control of flagellar motion, were generated and tested for binding to differentiated Caco 2 cells. Binding of the aEPEC strain to enterocytes was significantly impaired in strains with the fliCa nd fliD genes deleted, both of which could not form flagella on the bacterial surface. A nonmotile but flagellated MotAB mutant also showed impaired adhesion to Caco-2 cells. In accordance with these observations, adhesion of a EPEC strain 1711-4 to Caco-2 cells was drastically reduced after the treatment of Caco-2 cells with purified FliD. In addition, incubation of a EPEC bacteria with specific anti-FliD serum impaired binding to Caco-2 cells. Finally, incubation of Caco-2 cells with purified FliD, followed by immunolabeling, showed that the protein was specifically bound to the microvillus tips of differentiated Caco-2 cells. The a EPEC FliD or anti-FliD serum also reduced the adherence of prototype typical enteropathogenic, enterohemorrhagic, and enterotoxigenic E. coli strains to Caco-2 cells. In conclusion, our findings further strengthened the role of flagella in the adherence of a EPEC to human enterocytes and disclosed the relevant structural and functional involvement of FliD in the adhesion process. PMID- 26831467 TI - Perforin-2 Protects Host Cells and Mice by Restricting the Vacuole to Cytosol Transitioning of a Bacterial Pathogen. AB - The host-encoded Perforin-2 (encoded by the macrophage-expressed gene 1, Mpeg1), which possesses a pore-forming MACPF domain, reduces the viability of bacterial pathogens that reside within membrane-bound compartments. Here, it is shown that Perforin-2 also restricts the proliferation of the intracytosolic pathogen Listeria monocytogenes Within a few hours of systemic infection, the massive proliferation of L. monocytogenes in Perforin-2(-/-)mice leads to a rapid appearance of acute disease symptoms. We go on to show in cultured Perforin-2(-/ )cells that the vacuole-to-cytosol transitioning of L. monocytogenesis greatly accelerated. Unexpectedly, we found that in Perforin-2(-/-)macrophages,Listeria containing vacuoles quickly (<= 15 min) acidify, and that this was coincident with greater virulence gene expression, likely accounting for the more rapid translocation of L. monocytogenes to its replicative niche in the cytosol. This hypothesis was supported by our finding that aL. monocytogenes strain expressing virulence factors at a constitutively high level replicated equally well in Perforin-2(+/+)and Perforin-2(-/-)macrophages. Our findings suggest that the protective role of Perforin-2 against listeriosis is based on it limiting the intracellular replication of the pathogen. This cellular activity of Perforin-2 may derive from it regulating the acidification of Listeria-containing vacuoles, thereby depriving the pathogen of favorable intracellular conditions that promote its virulence gene activity. PMID- 26831468 TI - Characterization of SlyA in Shigella flexneri Identifies a Novel Role in Virulence. AB - The SlyA transcriptional regulator has important roles in the virulence and pathogenesis of several members of the Enterobacteriaceae family, including Salmonella enterica serovar Typhimurium and Escherichia coli. Despite the identification of the slyA gene in Shigella flexneri nearly 2 decades ago, as well as the significant conservation of SlyA among enteric bacteria, the role of SlyA in Shigella remains unknown. The genes regulated by SlyA in closely related organisms often are absent from or mutated inS. flexneri, and consequently many described SlyA-dependent phenotypes are not present. By characterizing the expression of slyA and determining its ultimate effect in this highly virulent organism, we postulated that novel SlyA-regulated virulence phenotypes would be identified. In this study, we report the first analysis of SlyA in Shigella and show that (i) the slyA gene is transcribed and ultimately translated into protein, (ii) slyA promoter activity is maximal during stationary phase and is negatively autoregulated and positively regulated by the PhoP response regulator, (iii) the exogenous expression of slyA rescues transcription and virulence associated deficiencies during virulence-repressed conditions, and (iv) the absence of slyA significantly decreases acid resistance, demonstrating a novel and important role in Shigella virulence. Cumulatively, our study illustrates unexpected parallels between the less conserved S. flexneri and S Typhimurium slyA promoters as well as a unique role for SlyA in Shigella virulence that has not been described previously in any closely related organism. PMID- 26831469 TI - Comparison of RELMalpha and RELMbeta Single- and Double-Gene-Deficient Mice Reveals that RELMalpha Expression Dictates Inflammation and Worm Expulsion in Hookworm Infection. AB - Resistin-like molecules (RELMs) are highly expressed following helminth infection, where they impact both the host and helminth. While RELMalpha (Retnla) impairs helminth expulsion by inhibiting protective Th2 immunity, RELMbeta (Retnlb) can promote its expulsion. We employed Retnla(-/-) and Retnlb(-/-) mice to delineate the function of both proteins following infection with Nippostrongylus brasiliensis, a hookworm that infects the lung and intestine. Whereas wild-type (WT) and Retnlb(-/-)mice exhibited equivalent infection-induced inflammation, Retnla(-/-) mice suffered a heightened inflammatory response, including increased mortality, weight loss, and lung inflammation. In the intestine, Retnla(-/-)mice had low parasite egg burdens compared to those of WT mice, while Retnlb(-/-) mice exhibited high egg burdens, suggesting that RELMalpha and RELMbeta have functionally distinct effects on immunity and inflammation to N. brasiliensis To test the importance of both proteins, we generated Retnla(-/-) Retnlb(-/-) mice. Infected Retnla(-/-)Retnlb(-/-) mice exhibited similar responses to Retnla(-/-) mice, including increased mortality and lung inflammation. This inflammatory response in Retnla(-/-) Retnlb(-/-) mice negatively impacted N. brasiliensis fitness, as demonstrated by significantly lower worm ATP levels and decreased intestinal worm burden and fecundity. Lung cytokine analysis revealed that Retnla(-/-) and Retnla(-/-) Retnlb(-/-) mice expressed significantly increased levels of interleukin-4 (IL-4). Finally, we generated Retnla(-/-) mice on the Rag(-/-) background and observed that the effects of RELMalpha were abrogated in the absence of adaptive immunity. Together, these data demonstrate that RELMalpha but not RELMbeta significantly impacts the immune response toN. brasiliensis infection by downregulating the Th2 adaptive immune response in the lung, which protects the host but allows improved parasite fitness. PMID- 26831471 TI - Morgagni's hernia in a hypoxaemic adult. PMID- 26831470 TI - Complement Activation by Giardia duodenalis Parasites through the Lectin Pathway Contributes to Mast Cell Responses and Parasite Control. AB - Infection with Giardia duodenalis is one of the most common causes of diarrheal disease in the world. While numerous studies have identified important contributions of adaptive immune responses to parasite control, much less work has examined innate immunity and its connections to the adaptive response during this infection. We explored the role of complement in immunity to Giardia using mice deficient in mannose-binding lectin (Mbl2) or complement factor 3a receptor (C3aR). Both strains exhibited delayed clearance of parasites and a reduced ability to recruit mast cells in the intestinal submucosa. C3aR-deficient mice had normal production of antiparasite IgA, butex vivo T cell recall responses were impaired. These data suggest that complement is a key factor in the innate recognition of Giardia and that recruitment of mast cells and activation of T cell immunity through C3a are important for parasite control. PMID- 26831473 TI - Child and parent engagement in therapy: What is the key? PMID- 26831472 TI - Global epidemiology of drug resistance after failure of WHO recommended first line regimens for adult HIV-1 infection: a multicentre retrospective cohort study. AB - BACKGROUND: Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART. METHODS: The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene. FINDINGS: We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1.50, 95% CI 1.27-1.77 for CD4 cell count <100 cells per MUL). Use of lamivudine versus emtricitabine increased the risk of tenofovir resistance across regions (OR 1.48, 95% CI 1.20-1.82). Of 700 individuals with tenofovir resistance, 578 (83%) had cytosine analogue resistance (M184V/I mutation), 543 (78%) had major NNRTI resistance, and 457 (65%) had both. The mean plasma viral load at virological failure was similar in individuals with and without tenofovir resistance (145 700 copies per mL [SE 12 480] versus 133 900 copies per mL [SE 16 650; p=0.626]). INTERPRETATION: We recorded drug resistance in a high proportion of patients after virological failure on a tenofovir-containing first-line regimen across low-income and middle-income regions. Effective surveillance for transmission of drug resistance is crucial. FUNDING: The Wellcome Trust. PMID- 26831474 TI - The Impact of Imaging Informatics Fellowships. AB - Imaging informatics (II) is an area within clinical informatics that is particularly important in the field of radiology. Provider groups have begun employing dedicated radiologist-informaticists to bridge medical, information technology and administrative functions, and academic institutions are meeting this demand through formal II fellowships. However, little is known about how these programs influence graduates' careers and perceptions about professional development. We electronically surveyed 26 graduates from US II fellowships and consensus leaders in the II community-many of whom were subspecialty diagnostic radiologists (68%) employed within academic institutions (48%)-about the perceived impact of II fellowships on career development and advancement. All graduates felt that II fellowship made them more valuable to employers, with the majority of reporting ongoing II roles (78%) and continued used of competencies (61%) and skills (56%) gained during fellowship in their current jobs. Other key benefits included access to mentors, protected time for academic work, networking opportunities, and positive impacts of annual compensation. Of respondents without II fellowship training, all would recommend fellowships to current trainees given the ability to gain a "still rare" but "essential skill set" that is "critical for future leaders in radiology" and "better job opportunities." While some respondents felt that II fellowships needed further formalization and standardization, most (85%) disagreed with requiring a 2-year II fellowship in order to qualify for board certification in clinical informatics. Instead, most believed that fellowships should be integrated with clinical residency or fellowship training while preserving formal didactics and unstructured project time. More work is needed to understand existing variations in II fellowship training structure and identify the optimal format for programs targeted at radiologists. PMID- 26831475 TI - Reoperation After Cervical Disc Arthroplasty Versus Anterior Cervical Discectomy and Fusion: A Meta-analysis. AB - BACKGROUND: Anterior cervical discectomy and fusion is a standard surgical treatment for cervical radiculopathy and myelopathy, but reoperations sometimes are performed to treat complications of fusion such as pseudarthrosis and adjacent-segment degeneration. A cervical disc arthroplasty is designed to preserve motion and avoid the shortcomings of fusion. Available evidence suggests that a cervical disc arthroplasty can provide pain relief and functional improvements similar or superior to an anterior cervical discectomy and fusion. However, there is controversy regarding whether a cervical disc arthroplasty can reduce the frequency of reoperations. QUESTIONS/PURPOSES: We performed a meta analysis of randomized controlled trials (RCTs) to compare cervical disc arthroplasty with anterior cervical discectomy and fusion regarding (1) the overall frequency of reoperation at the index and adjacent levels; (2) the frequency of reoperation at the index level; and (3) the frequency of reoperation at the adjacent levels. METHODS: PubMed, EMBASE, and the Cochrane Register of Controlled Trials databases were searched to identify RCTs comparing cervical disc arthroplasty with anterior cervical discectomy and fusion and reporting the frequency of reoperation. We also manually searched the reference lists of articles and reviews for possible relevant studies. Twelve RCTs with a total of 3234 randomized patients were included. Eight types of disc prostheses were used in the included studies. In the anterior cervical discectomy and fusion group, autograft was used in one study and allograft in 11 studies. Nine of 12 studies were industry sponsored. Pooled risk ratio (RR) and associated 95% CI were calculated for the frequency of reoperation using random-effects or fixed-effects models depending on the heterogeneity of the included studies. A funnel plot suggested the possible presence of publication bias in the available pool of studies; that is, the shape of the plot suggests that smaller negative or no difference studies may have been performed but have not been published, and so were not identified and included in this meta-analysis. RESULTS: The overall frequency of reoperation at the index and adjacent levels was lower in the cervical disc arthroplasty group (6%; 108/1762) than in the anterior cervical discectomy and fusion group (12%; 171/1472) (RR, 0.54; 95% CI, 0.36-0.80; p = 0.002). Subgroup analyses were performed according to secondary surgical level. Compared with anterior cervical discectomy and fusion, cervical disc arthroplasty was associated with fewer reoperations at the index level (RR, 0.50; 95% CI, 0.37 0.68; p < 0.001) and adjacent levels (RR, 0.52; 95% CI, 0.37-0.74; p < 0.001). CONCLUSIONS: Cervical disc arthroplasty is associated with fewer reoperations than anterior cervical discectomy and fusion, indicating that it is a safe and effective alternative to fusion for cervical radiculopathy and myelopathy. However, because of some limitations, these findings should be interpreted with caution. Additional studies are needed. LEVEL OF EVIDENCE: Level I, therapeutic study. PMID- 26831476 TI - Clinical Faceoff: Do We Need Special Strategies for Asian Patients with TKA? PMID- 26831477 TI - What Happens to the Articular Surface After Curettage for Epiphyseal Chondroblastoma? A Report on Functional Results, Arthritis, and Arthroplasty. AB - BACKGROUND: Chondroblastoma is an uncommon, benign, but locally aggressive bone tumor that occurs in the apophyses or epiphyses of long bones, primarily in young patients. Although some are treated with large resections, aggressive curettage and bone grafting are more commonly performed to preserve the involved joint. Such intralesional resection may result in damage to the growth plate and articular cartilage, which can result in painful arthritis. Prior studies have focused primarily on oncologic outcomes rather than long-term joint status and functional outcomes. QUESTIONS/PURPOSES: (1) What local complications can be expected after aggressive intralesional curettage of epiphyseal chondroblastoma? (2) What is the joint survival of a joint treated in this way for chondroblastoma? (3) What additional procedures are used in treating symptomatic joint osteoarthritis after treatment of the chondroblastoma? (4) What are the functional outcomes in this group of patients? METHODS: A retrospective study of our prospectively collected database between 1975 and 2013 was done. We found 64 patients with a diagnosis of chondroblastoma of bone. After applying our selection criteria, 53 patients were involved in this study. We excluded seven patients with tumors initially treated with en bloc resection (five located in the extremities and two in the axial skeleton) and two patients with apophyseal tumors. One patient who underwent nonsurgical treatment and one patient lost to followup were also excluded. The mean age was 18 years (range, 11-39 years); the minimum followup was 2 years with a mean followup 77 months (range, 24-213 months). We analyzed all patients with a diagnosis of epiphyseal chondroblastoma of the limb treated with aggressive curettage and joint preservation surgery. During the period in question, our general indications for curettage were patients with active, painful tumors and those with more aggressive ones that remained intracompartmental, whereas initial wide en bloc resection was indicated in patients who had tumors with an extracompartmental extension breaching the adjacent joint cartilage and massive articular destruction. The tumor location was the distal femur in 14 patients, proximal tibia in 11, proximal humerus in 10, proximal femur in eight, the talus in seven, and elsewhere in the lower extremity in three. Local complications including joint degeneration and tumor recurrence were evaluated. Based on radiographic analysis, secondary osteoarthritis was classified by using the Kellgren-Lawrence grading system from Grade 0 to Grade IV. Patients who underwent joint replacement resulting from advanced symptomatic osteoarthritis were considered to have had joint failure for purposes of survivorship analysis, which was estimated using the Kaplan-Meier method. Functional results were evaluated with the Musculoskeletal Tumor Society functional score by the treating surgeon, who transcribed the results on the digital records every 6 months of followup. RESULTS: Twenty-two patients (42%) developed 26 local complications. The most common local complication was osteoarthritis in 20 patients (77% [20 of 26 complications]); tumor recurrence was observed in four patients; an intraarticular fracture and superficial infection treated with surgical debridement and antibiotics developed in one patient each. Joint survival was 90% at 5 years (95% confidence interval [CI], 76%-100%) and 74% at 10 years (95% CI, 48%-100%). Proximal femoral tumor location was associated with lower survivorship of the joint than other locations showing a 5-year survival rate of 44% (95% CI, 0%-88%; p = 0.000). Of the 20 patients with osteoarthritis, four were symptomatic enough to undergo joint replacement, all of which were for tumors in the proximal femur. The mean Musculoskeletal Tumor Society functional score was 28 of 30 points (93%). CONCLUSIONS: Osteoarthritis was a frequent complication of aggressive curettage of epiphyseal chondroblastoma, and tumors located in the proximal femur appeared to be at particular risk of secondary osteoarthritis and prosthetic replacement. Because chondroblastoma is a tumor that disproportionately affects younger patients, the patient and surgeon should be aware that arthroplasty at a young age is a potential outcome for treatment of proximal femoral chondroblastomas. LEVEL OF EVIDENCE: Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence. PMID- 26831478 TI - Implant-delivered Alendronate Causes a Dose-dependent Response on Net Bone Formation Around Porous Titanium Implants in Canines. AB - BACKGROUND: Bony fixation of cementless orthopaedic implants is not always achieved, particularly in challenging scenarios such as revision surgery, trauma, and tumor reconstruction. An adjunct therapy for improving porous implant fixation could improve the reliability and durability of these reconstructive procedures. QUESTIONS/PURPOSES: In this study, we asked whether there is a positive and dose-dependent effect of the local release of the bisphosphonate alendronate from (1) alendronate/hydroxyapatite (HA) porous-coated titanium implants compared with bare metal porous controls; and (2) alendronate/HA on porous-coated titanium implants compared with HA-coated porous controls with respect to extent of bone ingrowth, bone apposition, and periimplant bone formation in a canine model? METHODS: Three-dimensional printed porous-coated cylindrical implants coated with three different doses (0.02, 0.06, and 0.18 mg/cm(2)) of alendronate were inserted bilaterally in the intramedullary canal of the proximal femora of 15 adult mongrel dogs (age range, 3-9 years; mean, 5 years) weighing between 36 kg and 60 kg (mean, 43 kg). In each dog, an implant coated with HA and one of three different doses of alendronate was inserted on one side while the contralateral femur had a bare metal porous control implant and an identical control implant with a coating of HA. The dose effect of locally released alendronate on the extent of bone ingrowth, bone apposition, and periimplant bone was assessed by backscattered electron microscopy of three pairs of cross-sections taken from each implant at 12 weeks after surgery. A linear mixed model was used to perform the statistical analyses to account for the correlation in the data resulting from the multiple measures performed on each dog. RESULTS: Compared with paired bare metal controls, periimplant bone increased by 92% (p = 0.007), and 114% (p < 0.001) in the femora with the alendronate implants with a dose of 0.06 mg/cm(2), or 0.18 mg/cm(2), respectively. At a dose of 0.02 mg/cm(2), there was no difference (46% change; p = 0.184, with the numbers available). The comparison of the alendronate-dosed implants with their HA-coated controls showed that the intermediate dose of 0.06 mg/cm(2) alendronate had the greatest effect on net bone formation. Bone apposition was enhanced with the 0.06-mg/cm(2) alendronate femoral implants (82%; p = 0.008), although there was no change in bone ingrowth (37% change; p = 0.902, with the numbers available). When compared with the HA-coated control implants, the greatest effect of the alendronate-dosed implants was the increased amount of periimplant bone at the intermediate dose of 0.06-mg/cm(2) (108%, p = 0.009). There was no effect of the low (0.02-mg/cm(2)) and high (0.18-mg/cm(2)) alendronate-dosed implants (4%, and 6%, respectively; p = 0.321, p = 0.502). Overall, all three alendronate-dosed implants revealed little to no effect on bone ingrowth compared with the HA-coated control implants. CONCLUSIONS: The local release of alendronate from a three-dimensional printed porous-coated implant from the three doses studied showed an overall improvement in bone apposition and periimplant bone at the intermediate dose compared with bare metal or with HA-coated controls, although the effect was more pronounced compared with bare metal. Long-term studies to show the effects of localized alendronate delivery and mechanical fixation would be the next step for future studies. CLINICAL RELEVANCE: Local release of alendronate from a three-dimensional printed porous-coated implant may improve the reliability of cementless fixation of currently available porous-coated bare metal implants. PMID- 26831480 TI - Acute Generalized Exanthematous Pustulosis Secondary to Acyclovir Confirmed by Positive Patch Testing. PMID- 26831479 TI - Antibiotic-tolerant Staphylococcus aureus Biofilm Persists on Arthroplasty Materials. AB - BACKGROUND: The continued presence of biofilm may be one cause of the high risk of failure observed with irrigation and debridement with component retention in acute periprosthetic joint infection (PJI). There is a poor understanding of the role of biofilm antibiotic tolerance in PJI. QUESTIONS/PURPOSES: (1) Do increasing doses of cefazolin result in decreased viable biofilm mass on arthroplasty materials? (2) Is cefazolin resistance phenotypic or genotypic? (3) Is biofilm viability a function of biofilm depth after treatment with cefazolin? (4) Is the toxin-antitoxin system, yoeB expression, associated with antibiotic stress? METHODS: Methicillin-sensitive Staphylococcus aureus biofilm was cultured on total knee arthroplasty (TKA) materials and exposed to increasing doses of cefazolin (control, 0.5, 1.0, 10.0, 100.0 MUg/mL). Quantitative confocal microscopy and quantitative culture were used to measure viable biofilm cell density. To determine if cefazolin resistance was phenotypic or genotypic, we measured minimum inhibitory concentration (MIC) after exposure to different cefazolin concentrations; changes in MIC would suggest genotypic features, whereas unchanged MIC would suggest phenotypic behavior. Finally, quantitative reverse transcription-polymerase chain reaction was used to quantify expression of yoeB levels between biofilm and planktonic bacteria after exposure to 1 MUg/mL cefazolin for 3 hours. RESULTS: Although live biofilm mass was reduced by exposure to cefazolin when compared with biofilm mass in controls (39.2 * 10(3) +/- 26.4 * 10(3) pixels), where the level after 0.5 ug/mL exposure also showed reduced mass (20.3 * 10(3) +/- 11.9 * 10(3) pixels), no further reduction was seen after higher doses (mass at 1.0 ug/mL: 5.0 * 10(3) pixels +/- 1.1 * 10(3) pixels; at 10.0 ug/mL: 6.4 * 10(3) +/- 9.6 * 10(3) pixels; at 100.0 ug/mL: 6.4 * 10(3) +/- 3.9 * 10(3)). At the highest concentration tested (100 ug/mL), residual viable biofilm was present on all three materials, and there were no differences in percent biofilm survival among cobalt-chromium (18.5% +/- 15.1%), polymethylmethacrylate (22.8% +/- 20.2%), and polyethylene (14.7% +/- 10.4%). We found that tolerance was a phenotypic phenomenon, because increasing cefazolin exposure did not result in changes in MIC as compared with controls (MIC in controls: 0.13 +/- 0.02; at 0.5 ug/mL: 0.13 +/- 0.001, p = 0.96; at 1.0 ug/m: 0.14 +/- 0.04, p = 0.95; at 10.0 ug/m: 0.11 +/- 0.016, p = 0.47; at 100.0 ug/m: 0.94 +/- 0.047, p = 0.47). Expression of yoeB after 1 ug/mL cefazolin for 3 hours in biofilm cells was greater in biofilm but not in planktonic cells (biofilm: 62.3-fold change, planktonic cells: -78.8-fold change, p < 0.001). CONCLUSIONS: Antibiotics are inadequate at complete removal of the biofilm from the surface of TKA materials. Results suggest that bacterial persisters are responsible for this phenotypic behavior allowing biofilm high tolerance to antibiotics. CLINICAL RELEVANCE: Antibiotic-tolerant biofilm suggests a mechanism behind the poor results in irrigation and debridement for acute TKA PJI. PMID- 26831482 TI - Detection and quantification of circulating immature platelets: agreement between flow cytometric and automated detection. AB - Immature platelets-also termed reticulated platelets (RP)-are platelets newly released into the circulation, and have been associated with a variety of pathological thrombotic events. They can be assessed by flow cytometry after staining with thiazole orange (TO) or by using a module added to a fully automated analyzer that is currently in wide clinical use and expressed as a fraction of the total platelet count (IPF). We sought to assess the correlation and agreement between these two methods. IPF was measured using Sysmex XE 2100 and at the same time point- we used TO staining and flow cytometry to measure RP levels. Two different gates were used for the flow cytometry method, 1 and 0.5 %. Measurements from the automated analyzer were then compared separately to measurements performed using each gate. Agreement between methods was assessed using Bland-Altman method. Pearson's correlation coefficient was also calculated. 129 subjects were enrolled and stratified into 5 groups: (1) Healthy subjects, (2) End stage renal disease, (3) Chronic stable coronary artery disease, (4) Post Coronary artery bypass surgery, (5) Peripheral thrombocytopenia. Median IPF levels were increased for patients in groups 2, 3, 4 and 5 (4.0, 4.7, 4.3, and 8.3 % respectively) compared to healthy subjects (2.5 %) p = 0.0001. Although the observed correlation between the two methods tended to be good in patients with high IPF values (i.e., group 5), the overall observed correlation was poor (Pearson's correlation coefficient r = 0.27). Furthermore, there was poor agreement between the two methods in all groups. Despite the good correlation that was observed between the two methods at higher IPF values, the lack of agreement was significant. PMID- 26831481 TI - Clinical presentations, risk factors, treatment and outcomes in patients with splanchnic vein thrombosis: a single-center experience. AB - Splanchnic vein thrombosis (SVT) is an uncommon form of venous thrombosis. Management can be challenging due to underlying conditions, increased bleeding risk, and lack of evidence from clinical trials. We sought to characterize the presentation and management of patients with SVT at a large tertiary hospital. A total of 43 patients' electronic medical records were reviewed. Median age at diagnosis was 43 (18-71). Sixteen patients had isolated portal vein thrombosis (37.2 %), and 16 (37.2 %) had thrombosis involving multiple splanchnic veins. Abdominal pain was the most common clinical presentation (67.4 %). Thrombophilia was present in 18 patients (41.9 %), nine had underlying liver disease (20.9 %) and seven had inflammatory bowel disease (16.3 %). Thirty-nine (90.7 %) patients were treated with anticoagulation, and 11(25.6 %) of these patients underwent interventional procedures. Thirty (69.8 %) patients remained on indefinite anticoagulation. Results of follow-up imaging at least 1 month after diagnosis were available for 29 patients; imaging showed chronic, stable thrombosis in 14 patients (48.3 %), resolution of thrombosis in 13 patients (44.8 %) and asymptomatic progression in two patients (6.9 %). Recurrent thrombosis occurred in four patients (9.3 %). Major bleeding occurred in eight patients who received anticoagulation (18.6 %), including fatal subdural hematoma in one patient. In this cohort of patients managed by hematologists and gastroenterologists, the majority of patients were treated with anticoagulation. Interventional procedures were higher than in previously reported series. Our study strongly supports the interdisciplinary management of splanchnic venous thrombosis. PMID- 26831483 TI - Promoting Healthy Eating Attitudes Among Uninsured Primary Care Patients. AB - Obesity is associated with a number of chronic health problems such as cardiovascular disease, diabetes and cancer. While common prevention and treatment strategies to control unhealthy weight gain tend to target behaviors and lifestyles, the psychological factors which affect eating behaviors among underserved populations also need to be further addressed and included in practice implementations. The purpose of this study is to examine positive and negative emotional valence about food among underserved populations in a primary care setting. Uninsured primary care patients (N = 621) participated in a self administered survey from September to December in 2015. Higher levels of perceived benefits of healthy food choice were associated with lower levels of a negative emotional valence about food while higher levels of perceived barriers to healthy food choice are related to higher levels of a negative emotional valence about food. Greater acceptance of motivation to eat was associated with higher levels of positive and negative emotional valence about food. Spanish speakers reported greater acceptance of motivation to eat and are more likely to have a negative emotional valence about food than US born or non-US born English speakers. The results of this study have important implications to promote healthy eating among underserved populations at a primary care setting. Healthy food choice or healthy eating may not always be achieved by increasing knowledge. Psychological interventions should be included to advance healthy food choice. PMID- 26831484 TI - Features in Grocery Stores that Motivate Shoppers to Buy Healthier Foods, ConsumerStyles 2014. AB - We examined nine features in grocery stores shoppers reported motivated them to purchase more healthful foods in the past month. Features were compiled from common supermarket practices for each of the 4 Ps of marketing: pricing, placement, promotion, and product. We examined percentages of the features overall and by shopping frequency using Chi square tests from a 2014 cross sectional web-based health attitudes and behaviors survey, ConsumerStyles. The survey was fielded from June to July in 2014. Participants were part of a market research consumer panel that were randomly recruited by probability-based sampling using address-based sampling methods to achieve a sample representative of the U.S. POPULATION: Data from 4242 adults ages 18 and older were analyzed. About 44 % of respondents indicated at least one feature motivated them to purchase more healthful foods. Top choices included in-store coupons or specials (20.1 %), availability of convenient, ready-to-eat more healthful foods (18.8 %), product labels or advertising on packages (15.2 %), and labels or signs on shelves that highlighted more healthful options (14.6 %). Frequent shoppers reported being motivated to purchase more healthful foods by in-store tastings/recipe demonstrations and coupons/specials more often than infrequent shoppers. Enhancing the visibility and appeal of more healthful food items in grocery stores may help improve dietary choices in some populations but additional research is needed to identify the most effective strategies for interventions. PMID- 26831485 TI - A Survey of African American Men in Chicago Barbershops: Implications for the Effectiveness of the Barbershop Model in the Health Promotion of African American Men. AB - The barbershop has been used to target African American (AA) men across age groups for health screenings, health interventions, and for research. However, few studies explore the sociodemographic characteristics of barbers and their clients. Additionally, few have evaluated the client's relative comfort with receiving health information and screenings in barbershops and other non-clinical settings. Lastly, it is unknown whether barbers feel capable of influencing health-decision making of AA men. AA male clients and barbers completed a self administered survey in barbershops in predominantly AA neighborhoods throughout Chicago, Illinois. We assessed sociodemographic characteristics and attitudes towards receiving physical and mental health education and screenings in barbershops and other settings. Barbers were also surveyed regarding their most and least common clients by age group and their perceived ability to influence the decision-making of AA males by age group. AAs surveyed in barbershops have similar rates of high school completion, poverty and unemployment as the AA residents of their neighborhood. AA males prefer to receive health education and screening in clinician offices followed by barbershops and churches. Barbers reported serving males age 18-39 years of age most frequently while men 50 years and older were the least served group. Overall, barbers did not believe they could influence the decision-making of AA men and in the best case scenario, only 33 % felt they could influence young men 18-29 years old. Barbershops reach AA men that are representative of the demographics of the neighborhood where the barbershop is located. Barbers reach a small population of men over age 49 and feel incapable of influencing the decisions of AAs over age 39. Further studies are needed to assess other locales for accessing older AA men and to evaluate the feasibility of mental health interventions and screenings within the barbershop. PMID- 26831486 TI - Fear as a Barrier to Asymptomatic Colonoscopy Screening in an Urban Minority Population with Health Insurance. AB - This study identified barriers to colonoscopy in a high-risk population and examined associations between barriers and both intention to comply with physician recommendation to receive colonoscopy and documented receipt of colonoscopy. Participants, enrollees in a randomized controlled trial assessing the effectiveness of educational interventions to promote colorectal cancer screening, were all 50+ years old and out of compliance with recommended screening guidelines. Direct financial cost of the procedure was not a barrier. The most commonly cited barriers were being afraid of the colonoscopy procedure (43.1 %), embarrassment (42.3 %), having to take a powerful laxative (36.2 %), fear of cancer (31.2 %), and fear of sedation (30.3 %). There were dose-response relationships between barriers and both intention to comply with physician recommendation of colonoscopy: 0, 1, 2, 3 barriers, 88.9, 79.0, 69.2 and 60.0 % intending to comply, respectively (linear trend chi(2) = 27.9, p = .000) and documented receipt of a colonoscopy: 0, 1, 2, 3 barriers, 21.7, 21.6, 8.5, 12.0 %, respectively (linear trend chi(2) = 8.4, p = .004). Only 6.9 % of the 102 expressing both fear of procedure and concern about taking a powerful laxative had a colonoscopy. These findings highlight the need to address patients' fear and suggest the importance of offering alternative colorectal cancer screening tests. ClinicalTrials.gov Identifier: NCT02392143. PMID- 26831487 TI - A MUSIC-based method for SSVEP signal processing. AB - The research on brain computer interfaces (BCIs) has become a hotspot in recent years because it offers benefit to disabled people to communicate with the outside world. Steady state visual evoked potential (SSVEP)-based BCIs are more widely used because of higher signal to noise ratio and greater information transfer rate compared with other BCI techniques. In this paper, a multiple signal classification based method was proposed for multi-dimensional SSVEP feature extraction. 2-second data epochs from four electrodes achieved excellent accuracy rates including idle state detection. In some asynchronous mode experiments, the recognition accuracy reached up to 100%. The experimental results showed that the proposed method attained good frequency resolution. In most situations, the recognition accuracy was higher than canonical correlation analysis, which is a typical method for multi-channel SSVEP signal processing. Also, a virtual keyboard was successfully controlled by different subjects in an unshielded environment, which proved the feasibility of the proposed method for multi-dimensional SSVEP signal processing in practical applications. PMID- 26831488 TI - A new method without reference channels used for ventricular fibrillation detection during cardiopulmonary resuscitation. AB - Ventricular fibrillation (VF) is observed as the initial rhythm in the majority of patients suffering from sudden cardiac arrest. It is vitally important to accurately recognize the initial VF rhythm and then implement electrical defibrillation. However, artifacts produced by chest compression during cardiopulmonary resuscitation (CPR) make the VF detection algorithms utilized by current automated external defibrillators (AEDs) unreliable. CPR must be traditionally interrupted for a reliable diagnosis. However, interruptions in chest compression have a deleterious effect on the success of defibrillation. The elimination of the CPR artifacts would enable compressions to continue during AED VF detection and thereby increase the likelihood of resuscitation success. We have estimated a model of this artifact by adaptively incorporating noise assisted multivariate empirical mode decomposition (NA-MEMD) and least mean squares (LMS) and then removing the artifact from the corrupted ECGs. The simulation experiment indicated that the CPR artifact could be accurately modeled without any reference channels. We constructed a BP neural network to evaluate the results. A total of 372 VF and 645 normal sinus rhythm (SR) ECG samples were included in the analysis, and 24 CPR artifact signals were used to construct corrupted ECGs. The results indicated that at different SNR levels ranging from 0 to -12 dB, the sensitivity and specificity were always above 95 and 80 %, respectively. PMID- 26831489 TI - Fatigue in Patients with Chronic Hepatitis B Living in North America: Results from the Hepatitis B Research Network (HBRN). AB - BACKGROUND: Fatigue is a common symptom of liver disease but not well characterized in patients with chronic hepatitis B virus (HBV). AIMS: We assessed the rate of fatigue using a validated instrument in patients with HBV and identified demographic, virologic, and clinical features associated with fatigue in a cross-sectional cohort study from the Hepatitis B Research Network. METHODS: Participants were English- and Spanish-speaking adults with chronic HBV who were not pregnant nor on treatment. Fatigue was measured using the PROMIS(r) Fatigue 7 item Short Form. RESULTS: The sample included 948 adults: median age 42; 51 % female; 71 % Asian; 74 % college educated; 77 % employed; 41 % inactive HBV carriers; 36 % with active chronic disease; and 2 % with advanced fibrosis, defined as AST-platelet ratio index (APRI) > 1.50. Patients with chronic HBV had a mean fatigue T-score of 46.8 +/- SD = 7.9, compared to a mean fatigue T-score of 50.0 +/- 10 in the US general population (p < .0001). In univariate analyses, greater fatigue was associated with demographic and clinical features such as female sex, lower income, more comorbidities, higher APRI score, and poorer mental health (p < 0.05). In multivariate analysis, female sex (p < .001), poorer mental health (p < .001), APRI score (p = .005), and history of diabetes (p = .039) were the strongest independent predictors. CONCLUSIONS: The frequency of fatigue in this large cohort of North American chronic HBV patients may be equal to or lower than that reported in the US general population. Patients with advanced fibrosis, more comorbidities, and poorer mental health report worse fatigue. PMID- 26831490 TI - Association Between Colorectal Cancer and Atherosclerotic Diseases: A Study Using a National Inpatient Database in Japan. AB - BACKGROUND: Both colorectal neoplasms and atherosclerosis can be induced by common visceral fat accumulation. However, the association between these diseases at the advanced stage, colorectal cancer and cardiovascular/cerebrovascular diseases, has not been elucidated. AIMS: This study aimed to investigate the association between colorectal cancer and vascular diseases in relation to obesity and metabolic disorders, using a nationwide database of hospitalized patients in Japan. We used non-cardiac gastric cancer patients as a reference, because they were considered to be neutral for obesity or metabolic disorders. METHODS: We identified 54,591 patients with colorectal cancer and 19,565 patients with gastric cancer from the Diagnosis Procedure Combination database. The data collected included: sex; age; body mass index (BMI); smoking status; comorbidity; and medication data, comprising hypertension, diabetes, hyperlipidemia, coronary artery disease, and stroke. We compared these data in a cross-sectional setting by multivariate analyses. RESULTS: Multivariate logistic regression analyses showed that female sex, increased BMI, hypertension [odds ratio (OR) 1.11; 95 % confidence interval (CI) 1.07-1.15; P < 0.0001], and diabetes (OR 1.17; 95 % CI 1.12-1.23; P < 0.0001) were more associated with colorectal cancer than with gastric cancer. Smoking, aspirin use (OR 0.85; 95 % CI 0.79-0.92; P < 0.0001), and coronary artery disease (OR 0.90; 95 % CI 0.86-0.95; P = 0.0001) were inversely associated with colorectal cancer. CONCLUSIONS: Obesity and metabolic disorders were more associated with colorectal cancer than with non-cardiac gastric cancer, while coronary artery disease (CAD) was inversely associated. Some mechanisms involving separate populations of colorectal cancer and CAD under visceral fat accumulation might be suggested. PMID- 26831491 TI - Neighborhood settings, types of social capital and depression among immigrants in Toronto. AB - PURPOSE: Few studies consider the associations between neighborhood social capital and immigrant's mental health. We examined associations between bonding, bridging and linking social capital and depression among immigrants in Toronto neighborhoods. METHODS: We used data on immigrants from the neighborhood effects on health and well-being (NEHW) study, conducted in 47 randomly selected greater Toronto area neighborhoods (sample = 916), and a study of one low-income, immigrant receiving neighborhood (IRN) (sample = 600). We conducted logistic regression models for depression (Epidemiologic Studies Depression Scale, CES-D) and social capital types: bonding (social cohesion and informal social control), bridging (group membership) and linking (engagement in political activities), while adjusting for different covariates. RESULTS: The prevalence of depression was 22.9 % in IRN and 21.4 % in NEHW. The associations between social capital types and depression differed in each sample. Lower social cohesion (bonding) was associated with higher depression in NEHW only. Lower linking social capital (never participated in political activities) was associated with lower depression in IRN only. These associations were consistent after adjustment for different covariates. CONCLUSIONS: Results suggest that social cohesion might have a protective effect from depression among immigrants in NEHW. In IRN, lower linking social capital associated with lower depression might reflect opposite direction association. Bridging social capital was not associated with depression in either sample, indicating that current community building might be insufficient to impact depression. Different pathways might explain how depression among immigrants is impacted by social capital types operating in different neighborhood settings; this could be examined in future longitudinal studies. PMID- 26831492 TI - Alcohol use, mental well-being, self-esteem and general self-efficacy among final year university students. AB - PURPOSE: We aimed to quantify associations between drinking and mental well being, self-esteem and general self-efficacy among New Zealand university students approaching graduation. METHODS: A web-based survey was conducted across all eight New Zealand universities in 2011. Participants were enrolled in their final year of a bachelor degree or a higher qualification and were aged 25 years and under (n = 5082, response level 65 %). Measures included the Alcohol Use Disorders Identification Test-Consumption, Warwick-Edinburgh Mental Well-being Scale, and items from the Rosenberg Self-esteem Scale and General Self-efficacy Scale. Linear regression models were used to estimate associations between the psychological measures and (1) drinking patterns for all participants (abstention/moderate/hazardous); and (2) consumption indicators for non abstaining participants (frequency/quantity/heavy drinking frequency), adjusting for a range of individual, social and personality characteristics, separately for men and women. RESULTS: Lower mental well-being was associated with a moderate or hazardous drinking pattern for men, and a hazardous pattern for women, compared to abstaining participants. Higher self-esteem was associated with any level of heavy drinking frequency for men, while the heaviest drinking women had a pattern of lower self-esteem. There was a general pattern of higher general self-efficacy for men and women who drank alcohol. CONCLUSIONS: We observed that higher levels of drinking were associated with small, yet statistically significant, differences in psychological outcomes for men and women. Our findings are of uncertain clinical significance; however, they underscore the importance of investigating a fuller range of social and personality factors that may confound the association of drinking and psychological outcomes. PMID- 26831494 TI - Response to letter to the editor: long-term visual outcome and prognostic factors of intravitreal antivascular endothelial growth factor treatment for retinal angiomatous proliferation. PMID- 26831493 TI - Methyl viologen induces neural differentiation on murine P19 cells. AB - Methyl viologen is a highly effective contact herbicide, a neurotoxic compound and an inducer of reactive oxygen species, which generate oxidative stress in cells. Reactive oxygen species has been known to function as an important messenger in cell differentiation. In this study, we investigated the effect of methyl viologen on neural cell differentiation using pluripotent mouse embryonal carcinoma P19 cells, which reportedly differentiate into neural cells upon exposure to retinoic acid. Methyl viologen, an inducer of intracellular reactive oxygen species, induced the differentiation of P19 cells into neural cells in the presence of neurofilament. Reduced glutathione, an eliminator of reactive oxygen species, also induced neural differentiation in P19 cells. These results suggest that P19 cells differentiate into neural cells, conceivably independent of intracellular reactive oxygen species. PMID- 26831495 TI - Nd:Yag laser goniopuncture for deep sclerectomy: efficacy and outcomes. AB - PURPOSE: To report on the safety and efficacy of Nd: YAG laser goniopuncture (LGP) for postsurgical intraocular pressure increase after deep sclerectomy (DS) in a consecutive cohort of open-angle glaucoma patients. METHODS: This case series included 56 eyes from 49 consecutive patients who underwent LGP between November 2008 and March 2015. Prior to LGP, patients had undergone DS augmented with mitomycin C and injectable cross-linked hyaluronic acid implant between October 2008 and May 2014. Demographic variables, type of glaucoma, prior phacoemulsification, intraocular pressure (IOP), best-corrected visual acuity, execution of post-LGP maneuvres, and post-LGP complications were analyzed. The success rate of the procedure was analyzed using the Kaplan-Meier survival curve. Univariate and multivariate analyses were performed using the Cox proportional hazard regression model in order to highlight variables associated with a failure to achieve surgical success. RESULTS: Mean IOP was 23.0 mmHg prior to LGP, and 12.5, 11.8, and 10.5 mmHg at 6, 12, and 24 months after LGP respectively. Post laser IOP was significantly lower than pre-laser IOP at every time point. For an IOP <= 15 mmHg, success rates were 85 % at 6 months, 76 % at 1 year, and 62 % at 2 years. Thirty-eight eyes underwent prophylactic iridotomy and iridoplasty prior to LGP. Iris prolapse into the trabeculo-descemetic window following LGP occurred in 6/18 eyes (33.3 %) of the non-pretreated and in 1/38 eyes (2.6 %) of the pretreated group. One case of choroidal detachment and one delayed suprachoroidal hemorrhage occurred after LGP execution in two non-pretreated eyes. CONCLUSIONS: LGP is a relatively safe and effective complementary adjunct to deep sclerectomy that makes it possible to further lower IOP and avoid additional filtering surgery. Prophylactic iridotomy and localized iridoplasty may permit the frequency of post-LGP complications to be reduced. PMID- 26831496 TI - A pilot study to compartmentalize small melanocytic choroidal tumors and choroidal vessels with speckle-noise free 1050 nm swept source optical coherence tomography (OCT choroidal "tumoropsy"). AB - PURPOSE: The purpose was to illustrate small melanocytic choroidal tumors with speckle-noise free swept-source optical coherence tomography (SSOCT). METHODS: Twenty-five small melanocytic choroidal tumors in 24 eyes underwent 1050 nm OCT. All tumors were measured manually with the built-in caliper tool and compared to data derived from a semiautomated algorithm that removed speckle noise but preserved the structure of the tumors from the SSOCT data. RESULTS: The average manual measurements for the horizontal, vertical, and axial diameters were 1535.28 MUm (range, 547-2807 MUm), 1713.8 MUm (range, 574-3921 MUm), and 227.28 MUm (range, 115-489 MUm), respectively. The measured average volumes of the tumors were 835,248,212 MUm(3) (range, 48,818,700 to 4,567,401,810 MUm(3)) and 228,588,535 MUm(3) (range, 22,879,641 to 787,668,886 MUm(3)) for caliper measurements, respectively, for the extracted volumes. The average volume variation between the two methods was 66.16 % (range, 46.5 % to 82.75 %). The average ratio between the caliper and extracted volumes was 3.402 (range, 1.346 8.198, SD 1.681), 2.367 (range, 1.346-3.258, SD 0.618), 2.321 (range, 1.346 3.258, SD 0.611), 2.402 (range, 1.518-3.258, SD 0.591), and 1.749 (range, 1.518 1.733, SD 0.239) for all tumors, all tumors with the exclusion of extreme parameters, tumor <3 mm, tumor <2 mm, and tumor <1 mm, respectively. The average ratio (tumor index) between the tumor volume and the choroidal vessel volume was 12.539 (range, 0.489-73.701). CONCLUSION: Speckle-noise free swept-source OCT may be an illustrative OCT imaging technology. OCT may be useful for describing and monitoring small melanocytic choroidal tumors and the choroidal vessels. PMID- 26831497 TI - Three new phosphates with isolated P2O7 units: noncentrosymmetric Cs2Ba3(P2O7)2 and centrosymmetric Cs2BaP2O7 and LiCsBaP2O7. AB - Three new phosphates, a noncentrosymmetric (NCS) Cs2Ba3(P2O7)2 and centrosymmetric (CS) Cs2BaP2O7 and LiCsBaP2O7, have been synthesized from high temperature solutions for the first time. Analysis of the structures determined by single-crystal X-ray diffraction showed that although the three compounds contained isolated P2O7 units, they yielded different three-dimensional (3D) networks: Cs2Ba3(P2O7)2 crystallized in the NCS Orthorhombic space group P212121, Cs2BaP2O7 in the CS monoclinic space group P21/n, and LiCsBaP2O7, having an identical stoichiometry with Cs2BaP2O7, crystallized in monoclinic space group, P21/c. Structural comparisons suggested the differences between their 3D frameworks to be due to differences between the sizes and coordination environments of the cations. Characterizations including thermal and optical analyses showed Cs2Ba3(P2O7)2 and Cs2BaP2O7 to melt congruently, and Cs2Ba3(P2O7)2 to exhibit a wide transparent region with a cut-off edge below 176 nm. The NLO properties and electronic structures of these compounds were investigated using first-principles calcualtions. PMID- 26831498 TI - Phase I trial of nedaplatin chemotherapy concurrent with radiotherapy for untreated locoregionally advanced nasopharyngeal carcinoma. AB - PURPOSE: In this phase I study, single-agent chemotherapy was conducted in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) using nedaplatin (NDP) and concomitant radiotherapy. The study sought to determine the maximum tolerated dose (MTD), recommended dose (RD) and the clinical efficacy of this treatment in locoregionally advanced NPC patients. EXPERIMENTAL DESIGN: Twenty patients were enrolled. The eligibility criteria included local advanced NPC (stage III or IVa) without any previous treatment and an expected survival of >= 3 months. The regimen consisted of 1.8-2.0 Gy daily radiation for 5 days a week and NDP with dose escalation of 70-100 mg/m(2) on day 1. The cycles were repeated every 21 days (day 1, day 22 and day 43) until the completion of chemoradiation. Dose-limiting toxicities (DLTs) included: grade 4 anemia; grade 4 neutropenia lasting for >= 5 days; grades 3 and 4 febrile neutropenia; grade 4 thrombocytopenia; grades 3-4 non-hematological toxicity (with the exception of alopecia, nausea) and any of the grade 5 responses. RESULTS: Ninety-five percent of the assessed patients experienced a treatment response. The median time to progression among all patients was 41.9 months. Two-year overall survival was 95%, while the progression-free survival was 85%. DLT included febrile neutropenia of grade 3. The RD of NDP was 90 mg/m(2) during cycles 1-3. CONCLUSION: NDP combined with radiotherapy and administered every 21 days for three cycles was active in patients with locoregionally advanced NPC. The regimen resulted in mild adverse effects and good patient compliance. Based on the findings from the study, the RD of NDP for phase II trial was found to be 90 mg/m(2). PMID- 26831499 TI - Melioidosis acquired by a traveler from Papua New Guinea. AB - Melioidosis is an infectious disease caused by Burkholderia pseudomallei. Melioidosis is of public health importance in endemic areas, particularly in tropical and sub-tropical areas. We describe a case of melioidosis contracted by a man with diabetes from Papua New Guinea that was evaluated using multi-locus sequence typing and whole genome sequencing. PMID- 26831500 TI - Exploring interprofessional collaboration during the integration of diabetes teams into primary care. AB - BACKGROUND: Specialised diabetes teams, specifically certified nurse and dietitian diabetes educator teams, are being integrated part-time into primary care to provide better care and support for Canadians living with diabetes. This practice model is being implemented throughout Canada in an effort to increase patient access to diabetes education, self-management training, and support. Interprofessional collaboration can have positive effects on both health processes and patient health outcomes, but few studies have explored how health professionals are introduced to and transition into this kind of interprofessional work. METHOD: Data from 18 interviews with diabetes educators, 16 primary care physicians, 23 educators' reflective journals, and 10 quarterly debriefing sessions were coded and analysed using a directed content analysis approach, facilitated by NVIVO software. RESULTS: Four major themes emerged related to challenges faced, strategies adopted, and benefits observed during this transition into interprofessional collaboration between diabetes educators and primary care physicians: (a) negotiating space, place, and role; (b) fostering working relationships; (c) performing collectively; and (d) enhancing knowledge exchange. CONCLUSIONS: Our findings provide insight into how healthcare professionals who have not traditionally worked together in primary care are collaborating to integrate health services essential for diabetes management. Based on the experiences and personal reflections of participants, establishing new ways of working requires negotiating space and place to practice, role clarification, and frequent and effective modes of formal and informal communication to nurture the development of trust and mutual respect, which are vital to success. PMID- 26831501 TI - Characteristics of morbidity and mortality conferences associated with the implementation of patient safety improvement initiatives, an observational study. AB - BACKGROUND: The aim of this study was to identify the characteristics of morbidity and mortality conferences (MMCs) associated with the implementation of patient health-care quality and safety improvement initiatives. METHODS: We conducted an observational study of MMCs and followed up improvement initiatives for 1 year. Data on MMC baseline characteristics were abstracted using document analysis and observation of a meeting in three university hospitals in France (Grenoble, Nice, and Cochin [Paris] hospitals). Fifty-nine MMCs were included in medical (n = 24), surgical (n = 21), and anesthesiology and/or intensive care (n = 14) departments. An effectiveness index was computed by summing a composite score for each initiative pertaining to the MMC. RESULTS: Overall, 282 initiatives were identified in 42 MMCs. During the follow-up period, 215 initiatives (76%) were totally or partially implemented and the impact was evaluated for 73 (26%). An effectiveness index higher than the median (i.e., >=10) was associated with a standardized presentation of cases (81% versus 29%, p <0.001), recording of improvement initiatives (94 versus 57, p = 0.001), the existence of an annual activity report (94% versus 68%, p = 0.01), the prior dissemination of a meeting agenda (71% versus 36%, p = 0.007), longer meeting duration (109 versus 80 min, p = 0.005), anesthesiology and/or intensive care specialty (39% versus 7%, p = 0.02), a theme-focused MMC (29% versus 4 %, p = 0.01), and a thorough analysis of failures (58% versus 25%, p = 0.01). CONCLUSIONS: This study suggests that the implementation of improvement initiatives relates to MCC characteristics. Recommendations for developing more effective patient safety-oriented MMCs can be proposed. PMID- 26831503 TI - The choice between hip prosthetic bearing surfaces in total hip replacement: a protocol for a systematic review and network meta-analysis. AB - BACKGROUND: Prosthetic hip implants have many combinations of bearing surface materials, sizes, and fixation techniques, which can determine the quality of life of patients after primary total hip replacement (THR) and the likelihood of needing revision surgery. When an implant fails, patients require revision THR, which is distressing to the patient and expensive for the health care payer. Primary THR is one of the most common elective procedures performed worldwide, with over 300,000 performed annually in the USA and over 80,000 in England and Wales. It is important to review all available randomised controlled trial (RCT) evidence to determine which implant bearing surface materials, size, and fixation technique are most effective for patients. METHODS/DESIGN: This is a protocol for a systematic review and meta-analysis of RCTs comparing outcomes of hip implant bearing surfaces, size, and fixation techniques used in THR. Implant combinations compared in the literature include four bearing surface combinations (metal-on polyethylene, metal-on-metal, ceramic-on-polyethylene, and ceramic-on-ceramic); two femoral head sizes (large vs small heads); and four fixation techniques (uncemented, cemented, hybrid, and reverse hybrids). The primary outcome will be revision surgery. We will also collect data on patient characteristics, mortality, quality of life, and other outcomes. In network meta-analysis, we will estimate the relative effectiveness of every implant bearing surface, head size (large vs small), and fixation permutation, using evidence where implants have been compared directly in an RCT and indirectly through common comparators in different RCTs. DISCUSSION: There has been much debate about materials used for prosthetic implants in THR. Different combinations of prosthetic materials, sizes, and fixation, can vary widely in cost and fail at different rates for different patient groups. Given the number of THRs performed yearly, and the increasing use of expensive implants, it is important to review evidence to inform surgeons, patients, and health care providers of optimal implant bearing combinations for given patient characteristics. This review will inform a cost effectiveness model that will include evidence from other sources, to determine the most effective and cost-effective implant bearing combination for patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015019435. PMID- 26831502 TI - Episodic fevers and vasodilatory shock mimicking urosepsis in a patient with HIV associated multicentric Castleman's Disease: a case report. AB - BACKGROUND: Multicentric Castleman's disease (MCD) is a pre-malignancy that presents with lymphadenopathy and features of systemic inflammation. Human immunodeficiency virus (HIV)-associated MCD is associated with human herpesvirus 8 (HHV-8) infection. If untreated MCD has a relapsing and remitting course that is eventually fatal. CASE PRESENTATION: A 67-year-old man had six hospital admissions over 20 months characterised by fever, urinary frequency and CRP >100 mg/L. The final admission was complicated by hypotension requiring intensive care unit admission and ionotropic support. His history included HIV and Hepatitis B virus (HBV) co-infection on suppressive therapy. Each presentation was managed as presumed urosepsis with use of empirical antibiotics, however numerous blood and urine cultures failed to identify a pathogen. A bone-marrow aspirate and trephine found no evidence of haematological malignancy. A positron emission tomography scan found active lymph nodes, one of which was biopsied and found to contain the plasma-cell variant of Castleman's disease. Ultimately the cause for the recurrent presentations was attributed to progressive MCD. The patient received rituximab monotherapy and has had no further related admissions. CONCLUSIONS: MCD should be considered in patients with chronic HIV infection presenting with recurrent sepsis-like episodes and/or vasodilatory shock, particularly if no pathogen is identified or lymphadenopathy is evident. PMID- 26831504 TI - Changed categorical perception of consonant-vowel syllables induced by transcranial direct current stimulation (tDCS). AB - BACKGROUND: Speech-related disorders may refer to impairment of temporal analysis in the human auditory system. By the advance of non-invasive brain stimulation new forms of therapy arise. In the present study, we examined the neuromodulatory effect of auditory tDCS on the perception of temporal modulated speech syllables. In three experimental sessions we assessed phonetic categorization of consonant vowels (CV)-syllables (/da/,/ta/) with varying voice onset times (VOT) during sham, anodal, and cathodal tDCS delivered bilateral to the auditory cortex (AC). Subsequently, we recorded auditory evoked potentials (AEP) in response to voiced (/ba/,/da/,/ga/) and voiceless (/pa/,/ta/,/ka/) CV-syllables. RESULTS: In result, we demonstrate that bilateral tDCS of the AC can modulate CV-syllable perception. Behaviorally, cathodal tDCS improved phonetic categorization abilities in a VOT continuum accompanied by an elevation of the P50 amplitude of the AEP to CV syllables during the anodal tDCS after effect. CONCLUSIONS: The present study demonstrates the ability of bilateral tDCS over the AC to ameliorate speech perception. The results may have clinical implications by fostering potential approaches for a treatment of speech-related pathologies with a deficit of temporal processing. PMID- 26831505 TI - The CATFISH study protocol: an evaluation of a water fluoridation scheme. AB - BACKGROUND: Tooth decay is the commonest disease of childhood. We have known for over 90 years that fluoride can prevent tooth decay; it is present in nearly all toothpastes and can be provided in mouthwashes, gels and varnishes. The oldest method of applying fluoride is via the water supply at a concentration of 1 part per million. The two most important reviews of water fluoridation in the United Kingdom (the York Review and MRC Report on water fluoridation and health) concluded that whilst there was evidence to suggest water fluoridation provided a benefit in caries reduction, there was a need to improve the evidence base in several areas. METHODS/DESIGN: This study will use a natural experiment to assess the incidence of caries in two geographical areas, one in which the water supply is returned to being fluoridated following a discontinuation of fluoridation and one that continues to have a non-fluoridated water supply. The oral health of two discrete study populations will be evaluated - those born 9 months after the water fluoridation was introduced, and those who were in their 1st year of school after the introduction of fluoridated water. Both populations will be followed prospectively for 5 years using a census approach in the exposed group along with matched numbers recruitment in a non-exposed control. Parents of the younger cohort will complete questionnaires every 6 months with child clinical examination at ages 3 and 5, whilst the older cohort will have clinical examinations only, at approximately 5, 7 and 11 years old. DISCUSSION: This project provides a unique opportunity to conduct a high quality evaluation of the reintroduction of a water fluoridation scheme, which satisfies the inclusion criteria stipulated by the York systematic review and can address the design issues identified in the MRC report. The research will make a major contribution to the understanding of the costs and effects of water fluoridation in the UK in the 21st Century. Its findings will help inform UK policy on this important public health intervention and may have a significant impact on public health policy in other developed countries. There is currently true equipoise in relation to the effectiveness of water fluoridation in contemporary populations and while the biological plausibility is well established, there is a need to examine impact on the changing epidemiological status of dental decay. PMID- 26831506 TI - Transcutaneous Electrical Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review. AB - CONTEXT: Transcutaneous electrical nerve stimulation (TENS) is a promising therapy for non-neurogenic lower urinary tract dysfunction and might also be a valuable option in patients with an underlying neurological disorder. OBJECTIVE: We systematically reviewed all available evidence on the efficacy and safety of TENS for treating neurogenic lower urinary tract dysfunction. EVIDENCE ACQUISITION: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. EVIDENCE SYNTHESIS: After screening 1943 articles, 22 studies (two randomised controlled trials, 14 prospective cohort studies, five retrospective case series, and one case report) enrolling 450 patients were included. Eleven studies reported on acute TENS and 11 on chronic TENS. In acute TENS and chronic TENS, the mean increase of maximum cystometric capacity ranged from 69ml to 163ml and from 4ml to 156ml, the mean change of bladder volume at first detrusor overactivity from a decrease of 13ml to an increase of 175ml and from an increase of 10ml to 120ml, a mean decrease of maximum detrusor pressure at first detrusor overactivity from 18 cmH20 to 72 cmH20 and 8 cmH20, and a mean decrease of maximum storage detrusor pressure from 20 cmH20 to 58 cmH2O and from 3 cmH20 to 8 cmH2O, respectively. In chronic TENS, a mean decrease in the number of voids and leakages per 24h ranged from 1 to 3 and from 0 to 4, a mean increase of maximum flow rate from 2ml/s to 7ml/s, and a mean change of postvoid residual from an increase of 26ml to a decrease of 85ml. No TENS-related serious adverse events have been reported. Risk of bias and confounding was high in most studies. CONCLUSIONS: Although preliminary data suggest TENS might be effective and safe for treating neurogenic lower urinary tract dysfunction, the evidence base is poor and more reliable data from well designed randomised controlled trials are needed to make definitive conclusions. PATIENT SUMMARY: Early data suggest that transcutaneous electrical nerve stimulation might be effective and safe for treating neurogenic lower urinary tract dysfunction, but more reliable evidence is required. PMID- 26831507 TI - alpha1-Blockers Improve Benign Prostatic Obstruction in Men with Lower Urinary Tract Symptoms: A Systematic Review and Meta-analysis of Urodynamic Studies. AB - CONTEXT: The urodynamic outcomes for alpha1-blockers (ABs) treatment in patients with lower urinary tract symptoms related to benign prostatic enlargement (LUTS/BPE) is a matter of debate. OBJECTIVE: To perform a systematic review and meta-analysis of studies evaluating the ABs urodynamic outcomes in patients with LUTS/BPE. The primary endpoint was variation in bladder outlet obstruction index (BOOI). Secondary endpoints were the maximum urinary flow rate (Qmax) and detrusor pressure at Qmax (PdetQmax). A meta-analysis of placebo-controlled randomized clinical trials (RCTs) was performed to compare ABs with placebo. EVIDENCE ACQUISITION: A systematic review of PubMed/Medline, ISI Web of Knowledge, and Scopus databases was performed in May 2015. Seventeen studies were selected for inclusion. EVIDENCE SYNTHESIS: The overall pooled data showed a mean BOOI change of -14.19 (p<0.0001), a mean PdetQmax change of -11. 39cm H2O (p<0.0001), and a mean Qmax improvement of 2.27ml/s (p<0.0001). Subgroup analysis showed a mean BOOI change of -14.88 (p=0.01) for alfuzosin, -19.41 (p=0.01) for doxazosin, -16.47 (p<0.0001) for naftopidil, -30.45 (p<0.0001) for silodosin, 14.27 (p=0.002) for tamsulosin, and -6.69 (p=0.005) for terazosin. Subanalysis of RCTs containing a placebo arm showed a significant improvement in BOOI in patients undergoing ABs treatment. Meta-regression revealed a significant positive association between the percentage of patients with obstruction at baseline and the improvement in BOOI after treatment with ABs. CONCLUSION: ABs improve BOOI in patients with LUTS/BPE mainly by reducing PdetQmax, and this effect is higher in patients presenting with urodynamic obstruction at baseline. The free Qmax variation underestimates the real effect of ABs on benign prostatic obstruction. PATIENT SUMMARY: Results of this meta-analysis suggest that alpha1 blockers objectively improve urinary voiding function in patients with benign prostatic obstruction. PMID- 26831510 TI - White middle class death rate rise is linked to common diseases. PMID- 26831508 TI - Early pneumonia and timing of antibiotic therapy in patients after nontraumatic out-of-hospital cardiac arrest. AB - BACKGROUND: While early pneumonia is common in patients after out-of-hospital cardiac arrest (OHCA), little is known about the impact of pneumonia and the optimal timing of antibiotic therapy after OHCA. METHODS: We conducted a 5-year retrospective cohort study, including patients who suffered from OHCA and were treated with therapeutic hypothermia. ICU treatment was strictly standardized with defined treatment goals and procedures. Medical records, chest radiographic images and microbiological findings were reviewed. RESULTS: Within the study period, 442 patients were admitted to our medical ICU after successfully resuscitated cardiac arrest. Of those, 174 patients fulfilled all inclusion and no exclusion criteria and were included into final analysis. Pneumonia within the first week could be confirmed in 39 patients (22.4%) and was confirmed or probable in 100 patients (57.5%), without a difference between survivors and non survivors (37.8% vs. 23.1% confirmed pneumonia, p = 0.125). In patients with confirmed pneumonia a tracheotomy was performed more frequently (28.2 vs. 12.6%, p = 0.026) compared to patients without confirmed pneumonia. Importantly, patients with confirmed pneumonia had a longer ICU- (14.0 [8.5-20.0] vs. 8.0 [5.0 14.0] days, p < 0.001) and hospital stay (23.0 [11.5-29.0] vs. 15.0 [6.5-25.0] days, p = 0.016). A positive end expiratory pressure (PEEP) > =10.5 mbar on day 1 of the hospital stay was identified as early predictor of confirmed pneumonia (odds ratio 2.898, p = 0.006). No other reliable predictor could be identified. Median time to antibiotic therapy was 8.7 [5.4-22.8] hours, without a difference between patients with or without confirmed pneumonia (p = 0.381) and without a difference between survivors and non-survivors (p = 0.264). Patients receiving antibiotics within 12 hours after admission had a shorter ICU- (8.0 [4.0-14.0] vs. 10.5 [6.0-16.0] vs. 13.5 [8.0-20.0] days, p = 0.004) and hospital-stay (14.0 [6.0-25.0] vs. 16.5 [11.0-27.0] vs. 21.0 [17.0-28.0] days, p = 0.007) compared to patients receiving antibiotics after 12 to 36 or more than 36 hours, respectively. CONCLUSIONS: Early pneumonia may extend length of ICU- and hospital stay after OHCA and its occurrence is difficult to predict. A delayed initiation of antibiotic therapy in OHCA patients may increase the duration of the ICU- and hospital-stay. PMID- 26831511 TI - Modifications to glucocorticoid and progesterone receptors alter cell fate in breast cancer. AB - Steroid hormone receptors (SRs) are heavily posttranslationally modified by the reversible addition of a variety of molecular moieties, including phosphorylation, acetylation, methylation, SUMOylation, and ubiquitination. These rapid and dynamic modifications may be combinatorial and interact (i.e. may be sequential, complement, or oppose each other), creating a vast array of uniquely modified receptor subspecies that allow for diverse receptor behaviors that enable highly sensitive and context-dependent hormone action. For example, in response to hormone or growth factor membrane-initiated signaling events, posttranslational modifications (PTMs) to SRs alter protein-protein interactions that govern the complex process of promoter or gene-set selection coupled to transcriptional repression or activation. Unique phosphorylation events allow SRs to associate or disassociate with specific cofactors that may include pioneer factors and other tethering partners, which specify the resulting transcriptome and ultimately change cell fate. The impact of PTMs on SR action is particularly profound in the context of breast tumorigenesis, in which frequent alterations in growth factor-initiated signaling pathways occur early and act as drivers of breast cancer progression toward endocrine resistance. In this article, with primary focus on breast cancer relevance, we review the mechanisms by which PTMs, including reversible phosphorylation events, regulate the closely related SRs, glucocorticoid receptor and progesterone receptor, allowing for precise biological responses to ever-changing hormonal stimuli. PMID- 26831512 TI - Reply to Letter From Floras et al.--Central Sleep Apnea: Risk Factor or Pathogenic Process in Patients With Heart Failure. PMID- 26831513 TI - Left Atrial Appendage Closure for Atrial Fibrillation Is Safe and Effective After Intracranial or Intraocular Hemorrhage. AB - BACKGROUND: Atrial fibrillation (AF) affects 1%-2% of the general population and 13% of individuals older than 80 years of age. Anticoagulation has been the mainstay therapy to reduce stroke risk. Patients with previous intracranial hemorrhage (ICH) or intraocular hemorrhage (IOH) are at increased risk of recurrence if anticoagulation is continued or initiated. Left atrial appendage (LAA) closure may obviate the need for long-term anticoagulation in these patients. METHODS: We report our consecutive series of patients with nonvalvular AF with previous ICH or IOH who underwent LAA closure with the AMPLATZER Cardiac Plug (ACP; St Jude Medical, St Paul, MN), AMPLATZER Amulet, or WATCHMAN (Boston Scientific, Natick, MA) device. Demographics, clinical status, procedural outcomes, and complications were collected at baseline, during the procedure, at 3 months, at 1 year, and annually thereafter. RESULTS: Twenty-six patients with previous ICH (n = 24) or IOH (n = 2) underwent LAA closure (9 with the ACP, 3 with the Amulet, and 7 with the WATCHMAN). The mean age was 76 +/- 7 years, and 61.5% were men with a mean CHADS2 (Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack) score of 3.2 +/- 1.4 and CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age [>= 75 years], Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age [65-74 years], Sex [Female] score) of 4.9 +/- 1.7. No procedure-related complications occurred. Mean follow-up was 11.9 +/- 13.3 months. One patient died at 13 months (this death was not related to the procedure), and 1 patient had a transient ischemic attack at 20.6 months after the procedure. No ischemic stroke, haemorrhagic stroke, or bleeding problems occurred during follow-up. CONCLUSIONS: In our consecutive series, LAA closure was found to be safe and effective in patients with AF and a history of ICH or IOH. PMID- 26831514 TI - A systematic evaluation of sorting motifs in the sodium-iodide symporter (NIS). AB - The sodium-iodide symporter (NIS) is an integral membrane protein that plays a crucial role in iodide accumulation, especially in the thyroid. As for many other membrane proteins, its intracellular sorting and distribution have a tremendous effect on its function, and constitute an important aspect of its regulation. Many short sequences have been shown to contribute to protein trafficking along the sorting or endocytic pathways. Using bioinformatics tools, we identified such potential sites on human NIS [tyrosine-based motifs, SH2-(Src homology 2), SH3- and PDZ (post-synaptic density-95/discs large tumour suppressor/zonula occludens 1)-binding motifs, and diacidic, dibasic and dileucine motifs] and analysed their roles using mutagenesis. We found that several of these sites play a role in protein stability and/or targeting to the membrane. Aside from the mutation at position 178 (SH2 plus tyrosine-based motif) that affects iodide uptake, the most drastic effect is associated with the mutation of an internal PDZ-binding motif at position 121 that completely abolishes NIS expression at the plasma membrane. Mutating the sites located on the C-terminal domain of the protein has no effect except for the creation of a diacidic motif that decreases the total NIS protein level without affecting its expression at the plasma membrane. PMID- 26831516 TI - The interaction between AMPKbeta2 and the PP1-targeting subunit R6 is dynamically regulated by intracellular glycogen content. AB - AMP-activated protein kinase (AMPK) is a metabolic stress-sensing kinase. We previously showed that glucose deprivation induces autophosphorylation of AMPKbeta at Thr-148, which prevents the binding of AMPK to glycogen. Furthermore, in MIN6 cells, AMPKbeta1 binds to R6 (PPP1R3D), a glycogen-targeting subunit of protein phosphatase type 1 (PP1), thereby regulating the glucose-induced inactivation of AMPK. In the present study, we further investigated the interaction of R6 with AMPKbeta and the possible dependency on Thr-148 phosphorylation status. Yeast two-hybrid (Y2H) analyses and co immunoprecipitation (IP) of the overexpressed proteins in human embryonic kidney (HEK) 293T) cells revealed that both AMPKbeta1 and AMPK-beta2 wild-type (WT) isoforms bind to R6. The AMPKbeta-R6 interaction was stronger with the muscle specific AMPKbeta2-WT and required association with the substrate-binding motif of R6. When HEK293T cells or C2C12 myotubes were cultured in high-glucose medium, AMPKbeta2-WT and R6 weakly interacted. In contrast, glycogen depletion significantly enhanced this protein interaction. Mutation of AMPKbeta2 Thr-148 prevented the interaction with R6 irrespective of the intracellular glycogen content. Treatment with the AMPK activator oligomycin enhanced the AMPKbeta2-R6 interaction in conjunction with increased Thr-148 phosphorylation in cells grown in low-glucose medium. These data are in accordance with R6 binding directly to AMPKbeta2 when both proteins detach from the diminishing glycogen particle, which is simultaneous with increased AMPKbeta2 Thr-148 autophosphorylation. Such a model points to a possible control of AMPK by PP1-R6 upon glycogen depletion in muscle. PMID- 26831517 TI - Replacement of Lost Lgr5-Positive Stem Cells through Plasticity of Their Enterocyte-Lineage Daughters. AB - Intestinal crypts display robust regeneration upon injury. The relatively rare secretory precursors can replace lost stem cells, but it is unknown if the abundant enterocyte progenitors that express the Alkaline phosphate intestinal (Alpi) gene also have this capacity. We created an Alpi-IRES-CreERT2 (Alpi(CreER)) knockin allele for lineage tracing. Marked clones consist entirely of enterocytes and are all lost from villus tips within days. Genetic fate mapping of Alpi(+) cells before or during targeted ablation of Lgr5-expressing stem cells generated numerous long-lived crypt-villus "ribbons," indicative of dedifferentiation of enterocyte precursors into Lgr5(+) stems. By single-cell analysis of dedifferentiating enterocytes, we observed the generation of Paneth like cells and proliferative stem cells. We conclude that the highly proliferative, short-lived enterocyte precursors serve as a large reservoir of potential stem cells during crypt regeneration. PMID- 26831515 TI - The anti-tumour agent lonidamine is a potent inhibitor of the mitochondrial pyruvate carrier and plasma membrane monocarboxylate transporters. AB - Lonidamine (LND) is an anti-tumour drug particularly effective at selectively sensitizing tumours to chemotherapy, hyperthermia and radiotherapy, although its precise mode of action remains unclear. It has been reported to perturb the bioenergetics of cells by inhibiting glycolysis and mitochondrial respiration, whereas indirect evidence suggests it may also inhibit L-lactic acid efflux from cells mediated by members of the proton-linked monocarboxylate transporter (MCT) family and also pyruvate uptake into the mitochondria by the mitochondrial pyruvate carrier (MPC). In the present study, we test these possibilities directly. We demonstrate that LND potently inhibits MPC activity in isolated rat liver mitochondria (Ki2.5 MUM) and co-operatively inhibits L-lactate transport by MCT1, MCT2 and MCT4 expressed in Xenopus laevisoocytes with K0.5 and Hill coefficient values of 36-40 MUM and 1.65-1.85 respectively. In rat heart mitochondria LND inhibited the MPC with similar potency and uncoupled oxidation of pyruvate was inhibited more effectively (IC50~ 7 MUM) than other substrates including glutamate (IC50~ 20 MUM). In isolated DB-1 melanoma cells 1-10 MUM LND increased L-lactate output, consistent with MPC inhibition, but higher concentrations (150 MUM) decreased L-lactate output whereas increasing intracellular [L-lactate] > 5-fold, consistent with MCT inhibition. We conclude that MPC inhibition is the most sensitive anti-tumour target for LND, with additional inhibitory effects on MCT-mediated L-lactic acid efflux and glutamine/glutamate oxidation. Together these actions can account for published data on the selective tumour effects of LND onL-lactate, intracellular pH (pHi) and ATP levels that can be partially mimicked by the established MPC and MCT inhibitor alpha-cyano-4-hydroxycinnamate (CHC). PMID- 26831518 TI - Bile Acids Protect Expanding Hematopoietic Stem Cells from Unfolded Protein Stress in Fetal Liver. AB - During development, hematopoietic stem cells (HSCs) undergo a rapid expansion in the fetal liver (FL) before settling in the adult bone marrow. We recently reported that proliferating adult HSCs are vulnerable to ER stress caused by accumulation of mis-folded proteins. Here, we find that FL-HSCs, despite an increased protein synthesis rate and a requirement for protein folding, do not upregulate ER chaperones. Instead, bile acids (BAs), secreted from maternal and fetal liver, coordinate to serve as chemical chaperones. Taurocholic acid, the major BA in FL, supports growth of HSCs in vitro by inhibiting protein aggregation. In vivo, reducing BA levels leads to ER stress elevation and accumulation of aggregated proteins and significantly decreases the number of FL HSCs. Taken together, these findings reveal that BA alleviation of ER stress is a mechanism required for HSC expansion during fetal hematopoiesis. PMID- 26831519 TI - Divergent natural selection promotes immigrant inviability at early and late stages of evolutionary divergence. AB - Natural selection's role in speciation has been of fundamental importance since Darwin first outlined his theory. Recently, work has focused on understanding how selection drives trait divergence, and subsequently reproductive isolation. "Immigrant inviability," a barrier that arises from selection against immigrants in their nonnative environment, appears to be of particular importance. Although immigrant inviability is likely ubiquitous, we know relatively little about how selection acts on traits to drive immigrant inviability, and how important immigrant inviability is at early-versus-late stages of divergence. We present a study evaluating the role of predation in the evolution of immigrant inviability in recently diverged population pairs and a well-established species pair of Brachyrhaphis fishes. We evaluate performance in a high-predation environment by assessing survival in the presence of a predator, and swimming endurance in a low predation environment. We find strong signatures of local adaptation and immigrant inviability of roughly the same magnitude both early and late in divergence. We find remarkably conserved selection for burst-speed swimming (important in predator evasion), and selection for increased size in low predation environments. Our results highlight the consistency with which selection acts during speciation, and suggest that similar factors might promote initial population differentiation and maintain differentiation at late stages of divergence. PMID- 26831524 TI - Tumour immunology: Neutrophils help tumours spread. PMID- 26831522 TI - High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients. AB - Intrathecal immunoglobulin G (IgG) synthesis and oligoclonal IgG bands in cerebrospinal fluid (CSF) are hallmarks of multiple sclerosis (MS), but the antigen specificities remain enigmatic. Our study is the first investigating the autoantibody repertoire in paired serum and CSF samples from patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and other neurological diseases by the use of high-density peptide microarrays. Protein sequences of 45 presumed MS autoantigens (e.g.MOG, MBP, and MAG) were represented on the microarrays by overlapping 15mer peptides. IgG reactivities were screened against a total of 3991 peptides, including also selected viral epitopes. The measured antibody reactivities were highly individual but correlated for matched serum and CSF samples. We found 54 peptides to be recognized significantly more often by serum or CSF antibodies from MS patients compared with controls (pvalues <0.05). The results for RRMS and PPMS clearly overlapped. However, PPMS patients presented a broader peptide-antibody signature. The highest signals were detected for a peptide mapping to a region of the Epstein-Barr virus protein EBNA1 (amino acids 392-411), which is homologous to the N-terminal part of human crystallin alpha-B. Our data confirmed several known MS-associated antigens and epitopes, and they delivered additional potential linear epitopes, which await further validation. The peripheral and intrathecal humoral immune response in MS is polyspecific and includes antibodies that are also found in serum of patients with other diseases. Further studies are required to assess the pathogenic relevance of autoreactive and anti-EBNA1 antibodies as well as their combinatorial value as biomarkers for MS. PMID- 26831525 TI - Immunometabolism: Unravelling the puzzle to longevity and immunity. PMID- 26831523 TI - Proteomic and Genomic Analyses of the Rvb1 and Rvb2 Interaction Network upon Deletion of R2TP Complex Components. AB - The highly conserved yeast R2TP complex, consisting of Rvb1, Rvb2, Pih1, and Tah1, participates in diverse cellular processes ranging from assembly of protein complexes to apoptosis. Rvb1 and Rvb2 are closely related proteins belonging to the AAA+ superfamily and are essential for cell survival. Although Rvbs have been shown to be associated with various protein complexes including the Ino80 and Swr1chromatin remodeling complexes, we performed a systematic quantitative proteomic analysis of their associated proteins and identified two additional complexes that associate with Rvb1 and Rvb2: the chaperonin-containing T-complex and the 19S regulatory particle of the proteasome complex. We also analyzed Rvb1 and Rvb2 purified from yeast strains devoid of PIH1 and TAH1. These analyses revealed that both Rvb1 and Rvb2 still associated with Hsp90 and were highly enriched with RNA polymerase II complex components. Our analyses also revealed that both Rvb1 and Rvb2 were recruited to the Ino80 and Swr1 chromatin remodeling complexes even in the absence of Pih1 and Tah1 proteins. Using further biochemical analysis, we showed that Rvb1 and Rvb2 directly interacted with Hsp90 as well as with the RNA polymerase II complex. RNA-Seq analysis of the deletion strains compared with the wild-type strains revealed an up-regulation of ribosome biogenesis and ribonucleoprotein complex biogenesis genes, down-regulation of response to abiotic stimulus genes, and down-regulation of response to temperature stimulus genes. A Gene Ontology analysis of the 80 proteins whose protein associations were altered in the PIH1 or TAH1 deletion strains found ribonucleoprotein complex proteins to be the most enriched category. This suggests an important function of the R2TP complex in ribonucleoprotein complex biogenesis at both the proteomic and genomic levels. Finally, these results demonstrate that deletion network analyses can provide novel insights into cellular systems. PMID- 26831526 TI - Immunological memory: lessons from the past and a look to the future. AB - Immunological memory is considered to be one of the cardinal features of the adaptive immune system. Despite being a recognized phenomenon since the time of the ancient Greeks, immunologists are yet to fully appreciate the mechanisms that control memory responses in the immune system. Furthermore, our definition of immunological memory itself continues to evolve, with recent suggestions that innate immune cells also show memory-like behaviour. In this Viewpoint article, Nature Reviews Immunology invites five leading immunologists to share their thoughts on our current understanding of the nature of immunological memory. Our experts highlight some of the seminal studies that have shaped the immune memory field and offer contrasting views on the key questions that remain to be addressed. PMID- 26831527 TI - Characteristics and Conflicts of Public Speakers at Meetings of the Oncologic Drugs Advisory Committee to the US Food and Drug Administration. PMID- 26831528 TI - Constipation in Duchenne Muscular Dystrophy: Prevalence, Diagnosis, and Treatment. AB - OBJECTIVES: To determine the prevalence and clinical characteristics of constipation among patients with Duchenne muscular dystrophy (DMD). STUDY DESIGN: This cross-sectional prospective study included 120 patients (age range 5-30 years old) with an established diagnosis of DMD. Participants filled out the constipation section of a validated Questionnaire on Pediatric Gastrointestinal Symptoms based on Rome-III Criteria (QPGS-RIII) for the diagnosis of functional constipation as part of a routine clinic visit. We evaluated several potential screening methods for constipation: the Bristol stool form scale, routine physical examination, and fecal load on abdominal radiograph. These methods were compared with the QPGS-RIII in diagnosing functional constipation. Risk factors for the development of functional constipation were determined. RESULTS: Based on the QPGS-RIII, 46.7% of patients with DMD in this cohort were diagnosed with functional constipation. Prevalence was not affected by age or functional status. None of the screening methods tested were sensitive enough to diagnose functional constipation. Among patients with constipation, only 43.6% received specific treatment for constipation and only one-half of these treated patients reported resolution of constipation. CONCLUSIONS: This study systematically examined constipation among patients with DMD and provides evidence that constipation among patients with DMD is highly prevalent, underdiagnosed, and undertreated. QPGS-RIII is easy to administer and is an efficient tool to diagnose functional constipation in patients with DMD in a clinic setting. PMID- 26831529 TI - Stakeholder Buy-In and Physician Education Improve Adherence to Guidelines for Down Syndrome. AB - OBJECTIVES: To assess adherence to the 2011 American Academy of Pediatrics (AAP) health supervision guidelines for Down syndrome, to determine whether pediatrician education improves adherence, and to evaluate stakeholder attitudes toward these guidelines. STUDY DESIGN: Twenty-two pediatric care sites participated in chart review of adherence to the components of the AAP guidelines for Down syndrome in this longitudinal cohort study. We analyzed universal recommendations which apply to all children with Down syndrome. Thirteen pediatric practices caring for 82 patients with Down syndrome received educational information. Frequency calculations with Bonferroni adjustment of the P value threshold (P = .05/9 = .0056) were performed. Adherence rates were compared between cohorts and within the individual before and after intervention using 2 * 2 contingency tables and goodness-of-fit tests. Pediatricians and parents of children with Down syndrome completed an anonymous survey regarding their attitudes toward the guidelines. RESULTS: Statistically significant increases in adherence were seen in 5 of the 8 universal recommendations following pediatrician education (P <= .002), including cardiology and genetics visits, rates of echocardiography, annual audiology testing, and sleep studies by age 4 years. Both physicians and parents reported generally positive views of the guidelines, yet baseline adherence rates were suboptimal. Pediatrician education preferences include directly integrating the guidelines into an electronic medical record system. CONCLUSION: Stakeholder attitudes reflect a willingness to follow the AAP guidelines for Down syndrome. Providing rapid access to simple, clear reminders of recommended assessments successfully improved adherence to the AAP guidelines for Down syndrome. PMID- 26831530 TI - Childhood cholecystectomy in New Zealand: A multicenter national 10year perspective. AB - AIM: International studies show increasing incidence of cholelithiasis in childhood and an increasing caseload for the pediatric surgeon. We reviewed pediatric cholecystectomy in all four centers in New Zealand, examining changes in incidence and the demographics of the patient population. METHOD: Coding data were used to retrieve case notes and extract demographic data, diagnosis, comorbidities, length of stay, and complications for patients less than 16years old undergoing cholecystectomy from January 1st, 2004-December 31st, 2013. Patients with congenital biliary malformations were excluded. Statistical analysis was performed using SPSS. RESULTS: 170 children required cholecystectomy. On average, 15 procedures were performed annually (IQR 8-24). There was a slight upward trend, with a gradient of 0.34 (P=0.63). Median age was 14 (range 2-15)years, male:female 2:3. While 72% of children were Caucasian, Maori were significantly overrepresented (20%). Numbers of Pacific Islander increased significantly over time (P=0.05), in line with population increases. Of 114 patients with complete dataset, 31% were overweight or obese. Complication rates were 8.8% overall, but 27% of complications occurred in Maori children. 40% of those suffering a complication were obese. Three complications were major, requiring return to theater. Mean length of stay was 5days. CONCLUSIONS: New Zealand has not seen the rapid increase in pediatric cholecystectomy experienced elsewhere in the OECD. However, the problem of adolescent biliary disease is prevalent. The average recipient of a cholecystectomy is 14years old, overweight, and Caucasian; though Maori have a high relative risk of both biliary disease and complicated postoperative course. The reasons for this remain unclear and require further study. PMID- 26831531 TI - Outcomes of thoracoscopic thymectomy in patients with juvenile myasthenia gravis. AB - INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disorder of the postsynaptic neuromuscular junction resulting in fatigability of voluntary muscles. There has been increasing evidence supporting thymectomy for MG in adults, and evidence for the role of surgery in pediatric age groups is increasing. The purpose of this study is to describe the outcomes of our patients with juvenile MG undergoing thoracoscopic thymectomy. MATERIAL AND METHODS: All patients with juvenile MG who underwent thoracoscopic thymectomy at Phoenix Children's Hospital between 1999 and 2014 were included. Patients were diagnosed by their treating neurologist. An Osserman and Genkins criterion was used to classify the severity of the disease and DeFilippi classification was used to assess remission. RESULTS: Twelve patients underwent thoracoscopic thymectomy for juvenile MG during the time frame studied. Nine (75%) patients had an Osserman stage of IIB, with only two patients with ocular disease. There were no conversions to an open procedure. Seven (59%) patients had normal thymic histology, 4 (33%) had evidence of follicular hyperplasia and one (8%) had involutional changes. The median length of hospital stay was 2days (range 1 5days). There was no 30-day postoperative morbidity, reoperations or mortality. The median length of follow-up was 31months (range, 4-91months) and at the time of their last follow-up; all 12 (100%) patients had a DeFilippi Classification of 3 or better. CONCLUSION: Surgery for MG in children is indicated for antibody receptor-positive patients with moderate to severe disease. Thoracoscopic thymectomy is a safe and acceptable treatment for juvenile MG with good disease control. The low morbidity and shorter hospital duration make it an excellent option for consideration. PMID- 26831532 TI - Younger gestational age is associated with increased risk of adverse neurodevelopmental outcome during infancy in congenital diaphragmatic hernia. AB - BACKGROUND: The purpose of the study was to investigate the impact of gestational age (GA) on short-term neurodevelopmental (ND) outcomes in congenital diaphragmatic hernia survivors. MATERIALS: Between 6/2004 and 2/2013, 135 consecutive CDH patients underwent ND assessment using the Bayley Scales of Infant Development-III at a median follow-up age of 13months (range, 5-36). ND delay was defined by a score of <=85 in any of the composite scales. Severe impairment was defined as a score of <=69 in at least one domain. The effect of GA was evaluated as continuous and categorical variables. GA at delivery was grouped into full term (39-41weeks), near term (37-38), late preterm (34-36), and preterm (24-33). RESULTS: Median GA at delivery was 38weeks (range, 24-41). Fifty (37%) patients were delivered full term, 59 (44%) near term, 16 (12%) late preterm, and 10 (7%) preterm. CDH children born before 39weeks' gestation were more likely to score below average (P=0.005) with corrected age for at least one composite score compared to full term peers. Cognitive (P=0.06) and language (P=0.08) scores tended to be lower in the near-term and late-preterm group compared to full-term CDH infants. Patients born near term and late preterm had significantly lower motor composite and fine motor scores compared to full-term children (P=0.009 and P<0.01, respectively). Preterm children scored the lowest in all composite scales (P<0.05). CONCLUSIONS: Compared to term infants, not only preterm but also late preterm and near-term CDH children carry an increased risk of ND delays. Motor performance appears most susceptible to earlier delivery. PMID- 26831533 TI - Routine contrast enema is not required for all infants prior to ostomy reversal: A 10-year single-center experience. AB - INTRODUCTION: The incidence of intestinal stricture is low for most conditions requiring a primary small bowel stoma in infants. Routine performance of contrast enemas (CE) prior to stoma closure adds cost and radiation exposure. We hypothesized that routine CE prior to ostomy reversal is not necessary in all infants, and sought to identify a subset of patients who may benefit from preoperative CE. METHODS: Medical records of infants under age 1 (N=161) undergoing small bowel stoma reversal at a single institution between 2003 and 2013 were retrospectively reviewed. Student's T-test was used to compare groups. RESULTS: Contrast enemas were performed on 80% of all infants undergoing small bowel ostomy reversal during the study period. Infants with necrotizing enterocolitis (NEC) were more likely to have a CE than those with intestinal atresia (p=0.03) or those with all other diagnoses combined (p=0.03). Nine strictures were identified on CE. Of those, 8 (89%) were in patients with NEC, and only 4 were clinically significant and required operative resection. The overall relevant stricture rate was 2.5%. No patient that underwent ostomy takedown without CE had a stricture diagnosed intraoperatively or an unrecognized stricture that presented clinically after stoma takedown. CONCLUSIONS: Routine CE is not required prior to small bowel ostomy reversal in infants. We recommend judicious use of enema studies in patients with NEC and high likelihood of stricture. PMID- 26831534 TI - The timing of surgical intervention in the treatment of complete motor paralysis in patients with spinal metastasis. AB - PURPOSE: The timing of surgical intervention is important for ambulatory patients with metastatic epidural spinal cord compression (MESCC), while limited studies have focused on non-ambulant patients. The aim of this study was to investigate the proper timing of surgical intervention for paraplegic patients with MESCC. METHODS: Forty-three non-ambulant patients with MESCC who underwent posterior decompression were retrospectively reviewed. The neurological outcomes for pre operative Frankel B patients with different interval window were further compared. RESULTS: Neurologic deficit improved by at least 1 Frankel grade in 37 patients who underwent surgery within 72 h (86.0 %). Overall, 18 pre-operative Frankel B patients became ambulatory again with an interval of less than 48 h, 15 pre-operative Frankel B patients remained non-ambulatory post-operatively with an interval longer than 48 h besides one with an interval of 8 h (P < 0.001). All nine pre-operative Frankel A patients remained non-ambulatory even though the interval window was less than 24 h. CONCLUSION: The timing of surgical intervention was key to predicting the post-operative outcome, and 48 h was suggested as the proper interval window for pre-operative Frankel B patients. These patients preserved sensory function which might be a predictor. And the sooner the surgery was performed, the better the result would be. PMID- 26831535 TI - Transpedicular surgical approach for the management of thoracic osteophyte induced intracranial hypotension refractory to non-operative modalities: case report and review of literature. AB - PURPOSE: In this article, we aim to describe the presentation and management of a case of spontaneous intracranial hypotension caused by a dural tear from a ventral thoracic osteophyte at the T12 level that was refractory to non-surgical treatment modalities. A review of the literature has been performed. Also a proposal of diagnostic and treatment algorithm is presented. Intracranial hypotension and CSF leak as a result of dural tear is a common phenomenon. However, the detection of the source of CSF leak from a thoracic spinal osteophyte has rarely been reported. METHODS: Diagnostic workup including MRI and CT Myelogram as well as application of epidural blood patches and surgical technique of hemilaminectomy and osteophytectomy by transpedicular approach have been described. Literature review was conducted using relevant search terms in PubMed. RESULTS: The patient's spontaneous intracranial hypotension symptoms resolved and this persisted on follow up visits. Review our experience as well as similar cases in the literature pointed us towards a diagnostic and treatment algorithm. CONCLUSIONS: Spontaneous resolution is the norm for intracranial hypotension of most etiologies and management of all such cases begins with fluid resuscitation coupled with bed rest. On failure of conservative therapy, autologous epidural blood patches into the spinal epidural space should be tried, which often produce an immediate relief of symptoms. Osteophyte-induced dural tear and consequent intracranial hypotension may require surgical intervention if the symptoms are refractory to conservative treatment. Under all circumstances a careful step-wise approach for diagnosis and treatment of spontaneous intracranial hypotension needs to be followed, as we have proposed in our article. PMID- 26831536 TI - Neck motion kinematics: an inter-tester reliability study using an interactive neck VR assessment in asymptomatic individuals. AB - BACKGROUND AND PURPOSE: The use of virtual reality (VR) for assessment and intervention of neck pain has previously been used and shown reliable for cervical range of motion measures. Neck VR enables analysis of task-oriented neck movement by stimulating responsive movements to external stimuli. Therefore, the purpose of this study was to establish inter-tester reliability of neck kinematic measures so that it can be used as a reliable assessment and treatment tool between clinicians. METHODS: This reliability study included 46 asymptomatic participants, who were assessed using the neck VR system which displayed an interactive VR scenario via a head-mounted device, controlled by neck movements. The objective of the interactive assessment was to hit 16 targets, randomly appearing in four directions, as fast as possible. Each participant was tested twice by two different testers. RESULTS: Good reliability was found of neck motion kinematic measures in flexion, extension, and rotation (0.64-0.93 inter class correlation). High reliability was shown for peak velocity globally (0.93), in left rotation (0.9), right rotation and extension (0.88), and flexion (0.86). Mean velocity had a good global reliability (0.84), except for left rotation directed movement with moderate reliability (0.68). Minimal detectable change for peak velocity ranged from 41 to 53 degrees /s, while mean velocity ranged from 20 to 25 degrees /s. CONCLUSIONS: The results suggest high reliability for peak and mean velocity as measured by the interactive Neck VR assessment of neck motion kinematics. VR appears to provide a reliable and more ecologically valid method of cervical motion evaluation than previous conventional methodologies. PMID- 26831537 TI - Modified translaminar screw fixation in the cervicothoracic junction (C7-T2): a technical note. AB - PURPOSE: To describe and illustrate a modified technique for using translaminar screw in the cervicothoracic junction (C7-T2). METHODS: 12 patients (8 males and 4 females, average age was 52 years) underwent insertion of unilateral or bilateral translaminar screws by using our modified technique. With this modified technique, a tiny unicortical "hole" was made at the middle of the contralateral lamina, and the screw can be directly visualized through the unicortical "hole" to prevent violating the spinal canal. RESULTS: With this modified technique, the mean operation time was 205 min (range 145-360) and mean estimated blood loss was 445 ml (range 260-1250). The mean length of the laminar screws was 27 (range 24 30) mm. The results of the 12 patients with an average follow-up of 17 (6-33) months demonstrated this modified technique to be safe and effective in the fixation of cervicothoracic junction. CONCLUSION: In this modified technique, a tiny unicortical "hole" which was made at the middle of the dorsal lamina of cervicothoracic junction (C7-T2). By directly visualizing the screw inserting against the dorsal cortices of the lamina, this modified technique can reduce the risk of violation of the spinal canal and shorten the operation time. PMID- 26831538 TI - Anatomical feasibility for safe occipital condyle screw fixation. AB - PURPOSE: The occipital condyle (OC) screw can be a viable alternative option for the occipito-cervical fixation. However, the risk of vertebral artery (VA) injury during the direct OC screw fixation has not been adequately assessed. The purpose of this study was to establish the course of the VA (V3) relative to the nearby osseous structures to estimate the feasibility of OC screw fixation and describe its anatomical relationship depending on patient's age and sex. METHODS: A total of 387 three-dimensional computed tomographic angiograms (3D-CTA) were used and compared between two age groups. The vertebral artery diameter and two kinds of bony space were measured. The occipito-C1 arch space (O-C1S) and VA-occipital bone distance (VOD, six entry points) were measured on both sides. The feasibility of direct OC screw fixation can be represented by the VOD value; the minimum feasible value was determined to be 4 mm. Angular measurements (O-C1A and O-C2A) were also taken to assess their relationship to the bony space. RESULTS: The mean value of the O-C1S ranged from 9.0 to 9.9 mm. The mean value of the VOD ranged from 3.2 to 3.5 mm, and the proportion of individuals for which direct OC screw fixation was considered feasible ranged from 32 to 42 % in both age groups and there was no significant difference between two age groups. The VOD value was not affected by laterality or by gender (P > 0.05). The mean kyphosis of the O C1A (-5 degrees +/- 5.2 degrees , range -22 degrees to 8 degrees ) was significantly smaller in the young age group compared to the older age group ( 7.6 degrees +/- 5.3 degrees , range -26 degrees to 2 degrees ). The mean lordosis of the O-C2A (12.4 degrees +/- 6.4 degrees , range 3 degrees -33 degrees ) was significantly higher in the young age group compared to the older age group (10.4 degrees +/- 6.4 degrees , range 0 degrees -36 degrees ). CONCLUSIONS: The direct OC screw fixation was not possible in a considerable number of cases due to the limited space and the position of the VA regardless of age group. Only about one quarter (21-24 %) of all patients was affordable to place the direct OC screw bilaterally. There was more space available to place the direct OC screw when the angle of the upper cervical spine is more kyphotic. PMID- 26831539 TI - Dimensions of the cervical neural foramen in conditions of spinal deformity: an ex vivo biomechanical investigation using specimen-specific CT imaging. AB - PURPOSE: Patients with cervical spondylosis commonly present with neck pain, radiculopathy or myelopathy. As degenerative changes progress, multiple factors including disc height loss, thoracic kyphosis, and facetogenic changes can increase the risk of neural structure compression. This study investigated the impact of cervical deformity including forward head posture (FHP) and upper thoracic kyphosis, on the anatomy of the cervical neural foramen. METHODS: Postural changes of 13 human cervical spine specimens (Occiput-T1, age 50.6 years; range 21-67) were assessed in response to prescribed cervical sagittal malalignments using a previously reported experimental model. Two characteristics of cervical sagittal deformities, C2-C7 sagittal vertical alignment (SVA) and sagittal angle of the T1 vertebra (T1 tilt), were varied to create various cervical malalignments. The postural changes were documented by measuring vertebral positions and orientations. The vertebral motion data were combined with specimen-specific CT-based anatomical models, which allowed assessments of foraminal areas of subaxial cervical segments as a function of increasing C2-C7 SVA and changing T1 tilt. RESULTS: Increasing C2-C7 SVA from neutral posture resulted in increased neural foraminal area in the lower cervical spine (largest increase at C4-C5: 13.8 +/- 15.7 %, P < 0.01). Increasing SVA from a hyperkyphotic posture (greater T1 tilt) also increased the neural foraminal area in the lower cervical segments (C5-C6 demonstrated the largest increase: 13.4 +/- 9.6 %, P < 0.01). The area of the cervical neural foramen decreased with increasing T1 tilt, with greater reduction occurring in the lower cervical spine, specifically at C5-C6 (-8.6 +/- 7.0 %, P < 0.01) and C6-C7 (-9.6 +/- 5.6 %, P < 0.01). CONCLUSION: An increase in thoracic kyphosis (T1 tilt) decreased cervical neural foraminal areas. In contrast, an increase in cervical SVA increased the lower cervical neural foraminal areas. Patients with increased upper thoracic kyphosis may respond with increased cervical SVA as a compensatory mechanism to increase their lower cervical neural foraminal area. PMID- 26831540 TI - The cohort study for the determination of reference values for spinopelvic parameters (T1 pelvic angle and global tilt) in elderly volunteers. AB - PURPOSE: T1 pelvic angle (TPA) and global tilt (GT) are spinopelvic parameters that account for trunk anteversion and pelvic retroversion. To investigate spinopelvic parameters, especially TPA and GT, in Japanese adults and determine norms for each parameter related to health-related quality of life (HRQOL). MATERIALS AND METHODS: Six hundred and fifty-six volunteers (262 men and 394 women) aged 50-92 years (mean, 72.8 years) were enrolled in this study. The incidence of vertebral fracture, spondylolisthesis and coronal malalignment were measured. Five spinopelvic parameters (TPA, GT, sagittal vertical axis [SVA], pelvic tilt [PT], and pelvic incidence-lumbar lordosis [PI-LL]) were measured using whole spine standing radiographs. The mean values for each parameter were estimated by sex and decade of life. HRQOL measures, including the Oswestry Disability Index (ODI) and EuroQuol-5D (EQ-5D), were also obtained. Pearson's correlation coefficients were determined between each parameter and HRQOL measure. Moreover, the factors contributing to the QOL score were calculated using logistic regression with age, sex, the existence of vertebral fracture and spondylolisthesis, coronal malalignment (coronal curve >30 degrees ) and sagittal malalignment (SVA >95 mm) as explanatory variables and the presence of disability (ODI >40) as a free variable. RESULTS: The mean values for the spinopelvic parameters were as follows: TPA, 17.9 degrees ; GT, 23.2 degrees ; SVA, 50.2 mm; PT, 18.6 degrees ; and PI-LL, 7.5 degrees . TPA and GT strongly correlated with each other (r = 0.990) and with the other spinopelvic parameters. TPA and GT correlated with ODI (r = 0.339, r = 0.348, respectively) and EQ-5D (r = -0.285, r = -0.288, respectively), similar to those for SVA. TPA, GT, PT, and PI-LL were significantly higher in women than in men. PT and PI-LL gradually increased with age, while TPA, GT, and SVA tended to deteriorate after the 7th decade. Based on a logistic regression analysis, the deterioration of ODI was mostly affected by the sagittal malalignment. The TPA and GT cut-off values for severe disability (ODI >40) based on linear regression modeling were 26.0 degrees and 33.7 degrees , respectively. CONCLUSIONS: We determined reference values for spinopelvic parameters in elderly volunteers. Similar to SVA, TPA and GT correlated with HRQOL. TPA, GT, PT, and PI-LL were worse in women and progressed with age. PMID- 26831541 TI - The effect of an oral anti-oxidant, N-Acetyl-cysteine, on inflammatory and oxidative markers in pulmonary sarcoidosis. AB - BACKGROUND: Oxidative stress (OS) has been shown to play a role in the pathogenesis of sarcoidosis and previous studies have shown that anti-oxidants can reduce markers of oxidative stress and inflammation in the peripheral blood of sarcoidosis subjects. We investigated the effect of N-Acetyl-Cysteine (NAC) on oxidative stress and inflammatory markers in the lungs of sarcoidosis patients. METHODS: We randomized 11 sarcoidosis subjects to active therapy and 3 to placebo for 8 weeks in a double blinded study. Bronchoscopy with bronchoalveolar lavage was performed pre and post therapy. Our primary endpoint was TNF-alpha production from stimulated and unstimulated BAL cells. Secondary outcomes included measures of oxidative stress (GSH, 8-OHdG) levels in the BAL. In-vitro studies were also performed to assess the effect of NAC on lipopolysaccharide stimulated BAL cell production of TNF-alpha. RESULTS: Eight subjects in the active group and 2 in the placebo group completed the study protocol. Eight weeks of oral NAC did not have a significant impact on TNF-alpha levels from BAL cells in-vivo in spite of a 59% increase in BAL GSH levels. Our in vitro studies showed a significant decline in TNF-alpha production from LPS stimulated BAL cells treated with 5 and 10 mM of NAC. CONCLUSIONS: Oral NAC increased GSH levels but failed to suppress in-vivo TNF-alpha production in contrast to effects in-vitro. Anti-oxidant therapy may still play a role in the management of sarcoidosis but therapy with better bioavailability or potency is needed to suppress the lung inflammatory response. PMID- 26831543 TI - [Kounis syndrome: A diagnostic urgency]. PMID- 26831542 TI - Decline in Weight and Incident Mild Cognitive Impairment: Mayo Clinic Study of Aging. AB - IMPORTANCE: Unintentional weight loss has been associated with risk of dementia. Because mild cognitive impairment (MCI) is a prodromal stage for dementia, we sought to evaluate whether changes in weight and body mass index (BMI) may predict incident MCI. OBJECTIVE: To investigate the association of change in weight and BMI with risk of MCI. DESIGN, SETTING, AND PARTICIPANTS: A population based, prospective study of participants 70 years of age or older from the Mayo Clinic Study of Aging, which was initiated on October 1, 2004. Maximum weight and height in midlife (40-65 years of age) were retrospectively ascertained from the medical records of participants using a medical records-linkage system. The statistical analyses were performed between January and November 2015. MAIN OUTCOMES AND MEASURES: Participants were evaluated for cognitive outcomes of normal cognition, MCI, or dementia at baseline and prospectively assessed for incident events at each 15-month evaluation. The association of rate of change in weight and BMI with risk of MCI was investigated using proportional hazards models. RESULTS: Over a mean follow-up of 4.4 years, 524 of 1895 cognitively normal participants developed incident MCI (50.3% were men; mean age, 78.5 years). The mean (SD) rate of weight change per decade from midlife to study entry was greater for participants who developed incident MCI vs those who remained cognitively normal (-2.0 [5.1] vs -1.2 [4.9] kg; P = .006). A greater decline in weight per decade was associated with an increased risk of incident MCI (hazard ratio [HR], 1.04 [95% CI, 1.02-1.06]; P < .001) after adjusting for sex, education, and apolipoprotein E (APOE) epsilon4 allele. A weight loss of 5 kg per decade corresponds to a 24% increase in risk of MCI (HR, 1.24). A higher decrease in BMI per decade was also associated with incident MCI (HR, 1.08 [95% CI, 1.03-1.13]; P = .003). CONCLUSIONS AND RELEVANCE: These findings suggest that increasing weight loss per decade from midlife to late life is a marker for MCI and may help identify persons at increased risk for MCI. PMID- 26831544 TI - [Safe practices for the use of opioids in patients with chronic pain]. PMID- 26831546 TI - Examining the role of Rh/Si cooperation in alkene hydrogenation by a pincer-type [P2Si]Rh complex. AB - A bis(phosphine)/triflatosilyl pincer-type Rh(i) complex can reversibly store one equivalent of H2 across the Si-Rh bond upon triflate migration from silicon to rhodium. The triflatosilyl complex serves as an effective precatalyst for norbornene hydrogenation, but Si-OTf bond cleavage is not implicated in the major catalytic pathway. The combined findings suggest possible strategies for M/Si cooperation in catalytic processes. PMID- 26831545 TI - Network-based in silico drug efficacy screening. AB - The increasing cost of drug development together with a significant drop in the number of new drug approvals raises the need for innovative approaches for target identification and efficacy prediction. Here, we take advantage of our increasing understanding of the network-based origins of diseases to introduce a drug disease proximity measure that quantifies the interplay between drugs targets and diseases. By correcting for the known biases of the interactome, proximity helps us uncover the therapeutic effect of drugs, as well as to distinguish palliative from effective treatments. Our analysis of 238 drugs used in 78 diseases indicates that the therapeutic effect of drugs is localized in a small network neighborhood of the disease genes and highlights efficacy issues for drugs used in Parkinson and several inflammatory disorders. Finally, network-based proximity allows us to predict novel drug-disease associations that offer unprecedented opportunities for drug repurposing and the detection of adverse effects. PMID- 26831547 TI - Extended-criteria donors in liver transplantation Part II: reviewing the impact of extended-criteria donors on the complications and outcomes of liver transplantation. AB - Extended-criteria donors (ECDs) have an impact on early allograft dysfunction (EAD), biliary complications, relapse of hepatitis C virus (HCV), and survivals. Early allograft dysfunction was frequently seen in grafts with moderate and severe steatosis. Donors after cardiac death (DCD) have been associated with higher rates of graft failure and biliary complications compared to donors after brain death. Extended warm ischemia, reperfusion injury and endothelial activation trigger a cascade, leading to microvascular thrombosis, resulting in biliary necrosis, cholangitis, and graft failure. The risk of HCV recurrence increased by donor age, and associated with using moderately and severely steatotic grafts. With the administration of protease inhibitors sustained virological response was achieved in majority of the patients. Donor risk index and EC donor scores (DS) are reported to be useful, to assess the outcome. The 1 year survival rates were 87% and 40% respectively, for donors with a DS of 0 and 3. Graft survival was excellent up to a DS of 2, however a DS >2 should be avoided in higher-risk recipients. The 1, 3 and 5-year survival of DCD recipients was comparable to optimal donors. However ECDs had minor survival means of 85%, 78.6%, and 72.3%. The graft survival of split liver transplantation (SLT) was comparable to that of whole liver orthotopic liver transplantation. SLT was not regarded as an ECD factor in the MELD era any more. Full-right-full-left split liver transplantation has a significant advantage to extend the high quality donor pool. Hypothermic oxygenated machine perfusion can be applied clinically in DCD liver grafts. Feasibility and safety were confirmed. Reperfusion injury was also rare in machine perfused DCD livers. PMID- 26831548 TI - The Role of Urbanization in Childhood Obesity. AB - Obesity is becoming the most frequently diagnosed chronic disease in many countries affecting all age groups and specifically the pediatric population. To date, most approaches have focused on changing the behavior of individuals with respect to diet and exercise. Almost all researchers agree that prevention could be the key strategy for controlling the current epidemic of obesity. Prevention may be achieved by changes in lifestyle through a variety of interventions targeting the urban environment, physical activity, time spent watching television and playing computer games and consumption of carbonated drinks. However, as yet, these strategies seem to have had little impact on the growing increase of the obesity epidemic. In this article, we aimed to discuss the effect of rapid urbanization on childhood obesity and to suggest solutions to this problem. PMID- 26831549 TI - Effect of Maternal Factors and Fetomaternal Glucose Homeostasis on Birth Weight and Postnatal Growth. AB - OBJECTIVE: It is important to identify the possible risk factors for the occurrence of large for gestational age (LGA) in newborns and to determine the effect of birth weight and metabolic parameters on subsequent growth. We aimed to determine the effects of maternal weight, weight gain during pregnancy, maternal hemoglobin A1c (HbA1c), C-peptide and insulin as well as cord C-peptide and insulin levels on birth weight and postnatal growth during the first two years of life. METHODS: Healthy, non-diabetic mothers and term singleton newborns were included in this prospective case-control cohort study. Fasting maternal glucose, HbA1c, C-peptide and insulin levels were studied. Cord blood was analyzed for C peptide and insulin. At birth, newborns were divided into two groups according to birth size: LGA and appropriate for GA (AGA). Infants were followed at six-month intervals for two years and their length and weight were recorded. RESULTS: Forty LGA and 43 AGA infants were included in the study. Birth weight standard deviation score (SDS) was positively correlated with maternal body mass index (BMI) before delivery (r=0.2, p=0.04) and with weight gain during pregnancy (r=0.2, p=0.04). In multivariate analyses, the strongest association with macrosomia was a maternal C-peptide level >3.85 ng/mL (OR=20). Although the LGA group showed decreased growth by the 6-month of follow-up, the differences between the LGA and AGA groups in weight and length SDS persisted over the 2 years of follow-up. CONCLUSION: The control of maternal BMI and prevention of overt weight gain during pregnancy may prevent excessive birth weight. The effect of the in utero metabolic environment on the weight and length SDS of infants born LGA persists until at least two years of age. PMID- 26831550 TI - Elevated Urinary T Helper 1 Chemokine Levels in Newly Diagnosed Hypertensive Obese Children. AB - OBJECTIVE: Increasing evidence suggests that T helper (Th) cells play a significant role in the pathogenesis of hypertension. The aim of this study was to evaluate the effect of obesity and anti-hypertensive treatment on urinary Th1 chemokines. METHODS: The study groups consisted of three types of patients: hypertensive obese, healthy, and non-hypertensive obese. Pre-treatment and post treatment samples of the hypertensive obese group and one sample from the other two groups were evaluated for urinary chemokine: regulated on activation, normal T cell expressed and secreted (RANTES), interferon-gamma-inducible protein 10 (IP10), and monokine induced by interferon-gamma (MIG). In the hypertensive obese group, urine microalbumin: creatinine ratio was examined before and after treatment. We recommended lifestyle changes to all patients. Captopril was started in those who could not be controlled with lifestyle changes and those who had stage 2 hypertension. RESULTS: Twenty-four hypertensive obese (mean age 13.1), 27 healthy (mean age 11.2) and 22 non-hypertensive obese (mean age 11.5) children were investigated. The pre-treatment urine albumin: creatinine ratio was positively correlated with pre-treatment MIG levels (r=0.41, p<0.05). RANTES was significantly higher in the pre-treatment hypertensive and non-hypertensive obese group than in the controls. The urinary IP10 and MIG levels were higher in the pre-treatment hypertensive obese group than in the non-hypertensive obese. Comparison of the pre- and post-treatment values indicated significant decreases in RANTES, IP10, and MIG levels in the hypertensive obese group (p<0.05). CONCLUSION: Th1 cells could be activated in obese hypertensive children before the onset of clinical indicators of target organ damage. Urinary RANTES seemed to be affected by both hypertension and obesity, and urinary IP10 and MIG seemed to be affected predominantly by hypertension. PMID- 26831552 TI - Plasma Kisspeptin Levels in Newborn Infants with Breast Enlargement. AB - OBJECTIVE: Kisspeptin levels have been reported in children with premature thelarche, precocious puberty and adolescent gynecomastia, but there are no reports on kisspeptin levels in the neonatal period. This study aimed to investigate plasma kisspeptin hormone levels in newborns with and without breast enlargement. METHODS: Plasma kisspeptin levels and other related biochemical variables were investigated in this prospective study conducted on 40 (20 girls and 20 boys) newborn infants with breast enlargement and on 40 healthy control infants (20 girls and 20 boys). Two-milliliter venous blood samples were taken in hemogram tubes with K2EDTA. Kisspeptin assays were performed using the enzyme immunoassay method. RESULTS: Mean plasma kisspeptin levels were 0.6 +/- 0.2 ng/mL in the study group and 0.5 +/- 0.2 ng/mL in the control group. Plasma kisspeptin concentrations were significantly higher in the study group (p=0.039) and also showed a correlation with serum prolactin levels (p=0.006). Significant correlations were also determined between plasma kisspeptin and luteinizing hormone concentrations (p=0.05, r=0.312). CONCLUSION: The findings of this study suggest that plasma kisspeptin and serum prolactin levels may be involved in the physiopathology of breast enlargement in newborns. PMID- 26831553 TI - Correlation of Brain Neuropeptide (Nesfatin-1 and Orexin-A) Concentrations with Anthropometric and Biochemical Parameters in Malnourished Children. AB - OBJECTIVE: Malnutrition continues to be a leading cause of stunted growth in many countries. This study aimed to investigate serum nesfatin-1 and orexin-A levels in underweight children and the potential correlations of these levels with anthropometric and nutritional parameters. METHODS: The study enrolled 44 prepubertal children (between 2 and 12 years of age) with thinness grades of 1-3 and 41 healthy age- and gender-matched children. The demographic, clinical and laboratory parameters including nesfatin-1 and orexin-A concentrations were compared between the two groups. The correlations of nesfatin-1 and orexin-A with biochemical and anthropometric parameters were investigated. The receiver operating characteristic (ROC) analysis were also performed for evaluating nesfatin-1 and orexin-A in distinguishing children with malnutrition from healthy controls. RESULTS: Thyroid-stimulating hormone, vitamin B12 and insulin levels were significantly lower in the study group than controls (p=0.001, p=0.049 and p=0.033, respectively). Mean nesfatin-1 levels in the malnourished group was also significantly lower compared to the healthy controls (3871.2 +/- 1608.8 vs. 5515.0 +/- 3816.4 pg/mL, p=0.012). No significant difference was observed in the orexin-A levels between the two groups (malnourished vs. control groups: 1135.7 +/- 306.0 vs. 1025.7 +/- 361.6 pg/mL, p=0.141). Correlation analyses revealed a positive correlation of nesfatin-1 and a negative correlation of orexin-A with body mass index (BMI) z-score. ROC analysis demonstrated that nesfatin-1 and orexin-A cannot be used to distinguish children with malnutrition from healthy controls (AUC: 0.620, p=0.061 for nesfatin-1 and AUC: 0.584, p=0.190 for orexin A). CONCLUSION: The positive correlation of nesfatin-1 and the negative correlation of orexin-A with BMI suggest that these neuropeptides may be a part of a protective mechanism in the maintenance of nutritional status and that they may have a role in regulating food intake in undernourished children. PMID- 26831554 TI - Effects of Diabetic Ketoacidosis on Visual and Verbal Neurocognitive Function in Young Patients Presenting with New-Onset Type 1 Diabetes. AB - OBJECTIVE: To evaluate the effects of diabetic ketoacidosis (DKA) on neurocognitive functions in children and adolescents presenting with new-onset type 1 diabetes. METHODS: Newly diagnosed patients were divided into two groups: those with DKA and those without DKA (non-DKA). Following metabolic stabilization, the patients took a mini-mental status exam prior to undergoing a baseline battery of cognitive tests that evaluated visual and verbal cognitive tasks. Follow-up testing was performed 8-12 weeks after diagnosis. Patients completed an IQ test at follow-up. RESULTS: There was no statistical difference between the DKA and non-DKA groups neither in alertness at baseline testing nor in an IQ test at follow-up. The DKA group had significantly lower baseline scores than the non-DKA group for the visual cognitive tasks of design recognition, design memory and the composite visual memory index (VMI). At follow-up, Design Recognition remained statistically lower in the DKA group, but the design memory and the VMI tasks returned to statistical parity between the two groups. No significant differences were found in verbal cognitive tasks at baseline or follow-up between the two groups. Direct correlations were present for the admission CO2 and the visual cognitive tasks of VMI, design memory and design recognition. Direct correlations were also present for admission pH and VMI, design memory and picture memory. CONCLUSION: Pediatric patients presenting with newly diagnosed type 1 diabetes and severe but uncomplicated DKA showed a definite trend for lower cognitive functioning when compared to the age-matched patients without DKA. PMID- 26831551 TI - Growth curves for Turkish Girls with Turner Syndrome: Results of the Turkish Turner Syndrome Study Group. AB - OBJECTIVE: Children with Turner syndrome (TS) have a specific growth pattern that is quite different from that of healthy children. Many countries have population specific growth charts for TS. Considering national and ethnic differences, we undertook this multicenter collaborative study to construct growth charts and reference values for height, weight and body mass index (BMI) from 3 years of age to adulthood for spontaneous growth of Turkish girls with TS. METHODS: Cross sectional height and weight data of 842 patients with TS, younger than 18 years of age and before starting any therapy, were evaluated. RESULTS: The data were processed to calculate the 3rd, 10th, 25th, 50th, 75th, 90th and 97th percentile values for defined ages and to construct growth curves for height-for-age, weight for-age and BMI-for-age of girls with TS. The growth pattern of TS girls in this series resembled the growth pattern of TS girls in other reports, but there were differences in height between our series and the others. CONCLUSION: This study provides disease-specific growth charts for Turkish girls with TS. These disease specific national growth charts will serve to improve the evaluation of growth and its management with growth-promoting therapeutic agents in TS patients. PMID- 26831555 TI - The Role of Thyrotropin-Releasing Hormone Stimulation Test in Management of Hyperthyrotropinemia in Infants. AB - OBJECTIVE: Hyperthyrotropinemia, which can be either a permanent or a transient state, is an asymptomatic condition and there is a controversy in management and long-term consequences. The aim of this study was to evaluate the results of thyrotropin-releasing hormone (TRH) test in infants with hyperthyrotropinemia. METHODS: Data of the patients who underwent a TRH test for mildly elevated thyroid-stimulating hormone (TSH) levels between 2004 and 2011 in a single academic pediatric endocrinology unit were retrospectively reviewed from the case files. RESULTS: Twenty infants (13 female, 7 male) with the median (range) age of 33 days (25-50) were enrolled into the study. The median basal TSH was 7.0 mIU/L (4.9-8.9) and free thyroxine level was 1.4 ng/mL (1.2-1.6) at the time of the TRH test. Thyroid ultrasonography was performed to 10 of the cases, and one of them had thyroid hypoplasia. TRH test revealed normal results in four infants, while sixteen infants had exaggerated response suggestive of primary hypothyroidism. The median follow-up period was 3.5 years (2.3-3.7). Therapy was discontinued in seven cases (2 had normal TRH response, 5 had exaggerated response) with the median age of 3.2 years (2.5-4). Of these seven infants, three had an elevated TSH on follow-up and L-thyroxine was restarted. All of the infants, in whom therapy was restarted, had exaggerated response to TRH. CONCLUSION: TRH test response could be a useful diagnostic test to evaluate the persistence of the disease during the infantile age period. PMID- 26831556 TI - Relationship Between Functional Exercise Capacity and Lung Functions in Obese Chidren. AB - OBJECTIVE: Cardiovascular, respiratory and musculoskeletal system disorders which may affect the functional exercise capacity are common in obese patients. We aimed to investigate the functional exercise capacity and its relationship with functional pulmonary capacity in obese children. METHODS: A total of 74 obese and 36 healthy children as a control group were enrolled in the study. Pulmonary functions and functional exercise capacity were measured by spirometry and six minute walk test (6 MWT), respectively. RESULTS: The distances covered during the 6 MWT in obese and control groups were 570.9 +/- 67.5 and 607.8 +/- 72.5 meters, respectively (p=0.010). In spirometric pulmonary function tests (PFTs), forced expiratory volume in 1 sec (FEV1) and forced mid-expiratory flows (25-75) were lower in the obese group (p=0.048 and p=0.047, respectively), whereas forced vital capacity (FVC), the FEV1/FVC ratio and peak expiratory flow were not statistically different between the obese and control groups. Multiple regression analysis revealed that among all parameters of anthropometric measures and PFTs, only body mass index standard deviation score (BMI-SDS) was the independent factor influencing 6 MWT. CONCLUSION: Functional exercise and lung capacities of obese children were diminished as compared to those of non-obese children. The most important factor influencing functional exercise capacity was BMI-SDS. PMID- 26831557 TI - Assessment of Cardiovascular Parameters in Obese Children and Adolescents with Non-Alcoholic Fatty Liver Disease. AB - OBJECTIVE: The aim of this study was to evaluate the periaortic fat thickness (PAFT) using conventional echocardiography in obese children and adolescents with non-alcoholic fatty liver disease (NAFLD). METHODS: Two hundred and ninety-seven obese children and adolescents were included in the study. Anthropometric measurements were made in all subjects, and fasting venous blood samples were taken for determination of glucose, insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Ultrasonography of the liver was used for assessment of NAFLD and the subjects were grouped as NAFLD and non-NAFLD. Echocardiography was performed in all subjects. RESULTS: PAFT was higher in patients with NAFLD compared with the non-NAFLD group. In patients with NAFLD, PAFT was positively correlated with waist circumference and with total cholesterol levels. In multiple regression analysis, waist circumference (beta=0.28, p=<0.001) was found to be the best predictor of PAFT. CONCLUSION: Conventional echocardiography may be used to determine increased PAFT at an early stage in obese children and adolescents with NAFLD for careful monitoring of cardiovascular risk. PMID- 26831558 TI - Prevalence of Dyslipidemia and Associated Factors in Obese Children and Adolescents. AB - OBJECTIVE: Childhood-onset obesity is associated with increased mortality and morbidity related to cardiovascular diseases (CVD) during adulthood. Dyslipidemia has a fundamental role in the pathogenesis of CVD. This study aimed to evaluate the prevalence of dyslipidemia and related factors among obese children and adolescents. METHODS: Obese patients aged between 2 and 18 years were included in the study. Serum concentrations of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), fasting glucose levels, insulin, thyroid-stimulating hormone (TSH), free thyroxine (fT4), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and liver ultrasound findings were evaluated retrospectively. RESULTS: Among 823 obese patients, 353 (42.9%) met the dyslipidemia criteria: 21.7% had hypertriglyceridemia, 19.7% had low levels of HDL-C, 18.6% had hypercholesterolemia, and 13.7% had high levels of LDL-C. Older age and/or high body mass index (BMI) were related to increased prevalence of dyslipidemia. Hepatosteatosis was more common among dyslipidemic patients. The frequency of insulin resistance (IR) and of higher levels of ALT and TSH were also detected in dyslipidemic patients. Patients with both dyslipidemia and grade 2-3 hepatosteatosis had higher levels of ALT, AST and TSH and lower levels of fT4. CONCLUSION: Prevalence of dyslipidemia is high in obese children, and hypertriglyceridemia is in the foreground. Higher levels of IR and more apparent abnormal liver function test results are observed in the context of dyslipidemia and hepatosteatosis coexistence. Metabolic and hormonal alterations related with thyroid functions may also be associated with dyslipidemia and hepatosteatosis in obese patients. PMID- 26831559 TI - Relationship Between Timing of Peak Height Velocity and Pubertal Staging in Boys and Girls. AB - Growth and pubertal development are important health markers. We used the data of a longitudinal growth study on a contemporary sample of US youth to examine the relationship between peak height velocity (PHV) and Tanner staging. We observed a substantial variability in the timing of PHV across Tanner stages, which is an important consideration for clinicians when assessing growth. PMID- 26831560 TI - The Missense Alteration A5T of the Thyroid Peroxidase Gene is Pathogenic and Associated with Mild Congenital Hypothyroidism. AB - Congenital hypothyroidism (CH) occurs with a prevalence of approximately 1:4000 live births. Defects of thyroid hormone synthesis account for 15-20% of these cases. Thyroid peroxidase (TPO) gene is the most common cause for dyshormonogenesis. So far, more than 60 mutations in the TPO gene have been described, resulting in a variable decrease in TPO bioactivity. We present an 8 day-old male with mild CH who was identified to have a G to A transition in the fifth codon of the TPO gene (c.13G>A; p.Ala5Thr). The unaffected family members were heterozygous carriers of the mutation, whereas 400 healthy individuals of the same ethnic background did not have the mutation. Mutation analysis of 11 known causative CH genes and 4 of our own strong candidate genes with next generation sequencing revealed no mutations in the patient nor in any other family members. The results of in silico functional analyses indicated partial loss-of-function (LOF) in the resulting enzyme molecule due to mutation. The patient's clinical finding s were consistent with the effect of this partial LOF of the mutation. In conclusion, we strongly believe that A5T alteration in the TPO gene is actually pathogenic and suggest that it should be classified as a mutation. PMID- 26831561 TI - Testotoxicosis: Report of Two Cases, One with a Novel Mutation in LHCGR Gene. AB - Testotoxicosis is a rare disorder which presents as isosexual peripheral precocious puberty in males. Despite the pattern of autosomal dominant inheritance, sporadic cases also may occur. Due to activating mutation in luteinizing hormone (LH))/choriogonadotropin receptor (LHCGR) gene, early virilization and advancement in bone age are common with increased serum testosterone levels above adult ranges, despite low LH and follicular-stimulating hormone (FSH) levels. There are different treatment regimens, such as combination of bicalutamide (antiandrogen agent) and a third-generation aromatase inhibitor, that are reported to be well-tolerated and successful in slowing bone age advancement and preventing progression of virilization. We report here two patients who presented with peripheral precocious puberty and an activating mutation in the LHCGR gene: one with a family history and previously determined mutation and the other without family history and with a novel mutation (c.830G>T). Combination of bicalutamide+anastrozole was ineffective in slowing pubertal progression and bone age. Short-term results were better with ketoconazole. PMID- 26831562 TI - Severe Undervirilisation in a 46,XY Case Due to a Novel Mutation in HSD17B3 Gene. AB - 17-beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD3) is an important enzyme involved in the final steps of androgen synthesis and is required for the development of normal male external genitalia. 46,XY individuals with deficiency of this enzyme present a wide clinical spectrum from a female appearance of the external genitalia through ambiguous genitalia to a predominantly male genitalia with micropenis or hypospadias. This paper reports a one-year-old 46,XY patient with 17beta-HSD3 deficiency who presented with female external genitalia and bilaterally palpable gonads in the inguinal region. The low T/Delta4 ratio after human chorionic gonadotropin (hCG) stimulation suggested 17beta-HSD3 deficiency. A homozygous mutation, c.761_762delAG, was determined at the intron 9/exon 10 splice site of the HSD17B3 gene. To the best of our knowledge, this mutation has not been reported thus far, but its localization and type would imply a complete disruption of the 17beta-HSD3 which may explain the phenotype of our patient. PMID- 26831563 TI - The use of sub-critical water hydrolysis for the recovery of peptides and free amino acids from food processing wastes. Review of sources and main parameters. AB - Food industry processing wastes are produced in enormous amounts every year, such wastes are usually disposed with the corresponding economical cost it implies, in the best scenario they can be used for pet food or composting. However new promising technologies and tools have been developed in the last years aimed at recovering valuable compounds from this type of materials. In particular, sub critical water hydrolysis (SWH) has been revealed as an interesting way for recovering high added-value molecules, and its applications have been broadly referred in the bibliography. Special interest has been focused on recovering protein hydrolysates in form of peptides or amino acids, from both animal and vegetable wastes, by means of SWH. These recovered biomolecules have a capital importance in fields such as biotechnology research, nutraceuticals, and above all in food industry, where such products can be applied with very different objectives. Present work reviews the current state of art of using sub-critical water hydrolysis for protein recovering from food industry wastes. Key parameters as reaction time, temperature, amino acid degradation and kinetic constants have been discussed. Besides, the characteristics of the raw material and the type of products that can be obtained depending on the substrate have been reviewed. Finally, the application of these hydrolysates based on their functional properties and antioxidant activity is described. PMID- 26831564 TI - Impact of socioeconomic status on municipal solid waste generation rate. AB - The solid waste generation rate was expected to vary in different socioeconomic groups due to many environmental and social factors. This paper reports the assessment of solid waste generation based on different socioeconomic parameters like education, occupation, income of the family, number of family members etc. A questionnaire survey was conducted in the study area to identify the different socioeconomic groups that may affect the solid waste generation rate and composition. The average waste generated in the municipality is 0.41 kg/capita/day in which the maximum waste was found to be generated by lower middle socioeconomic group (LMSEG) with average waste generation of 0.46 kg/capita/day. Waste characterization indicated that there was no much difference in the composition of wastes among different socioeconomic groups except ash residue and plastic. Ash residue is found to increase as we move lower down the socioeconomic groups with maximum (31%) in lower socioeconomic group (LSEG). The study area is a coal based city hence application of coal and wood as fuel for cooking in the lower socioeconomic group is the reason for high amount of ash content. Plastic waste is maximum (15%) in higher socioeconomic group (HSEG) and minimum (1%) in LSEG. Food waste is a major component of generated waste in almost every socioeconomic group with maximum (38%) in case of HSEG and minimum (28%) in LSEG. This study provides new insights on the role of various socioeconomic parameters on generation of household wastes. PMID- 26831565 TI - Molecular sled is an eleven-amino acid vehicle facilitating biochemical interactions via sliding components along DNA. AB - Recently, we showed the adenovirus proteinase interacts productively with its protein substrates in vitro and in vivo in nascent virus particles via one dimensional diffusion along the viral DNA. The mechanism by which this occurs has heretofore been unknown. We show sliding of these proteins along DNA occurs on a new vehicle in molecular biology, a 'molecular sled' named pVIc. This 11-amino acid viral peptide binds to DNA independent of sequence. pVIc slides on DNA, exhibiting the fastest one-dimensional diffusion constant, 26+/-1.8 * 10(6) (bp)(2) s(-1). pVIc is a 'molecular sled,' because it can slide heterologous cargos along DNA, for example, a streptavidin tetramer. Similar peptides, for example, from the C terminus of beta-actin or NLSIII of the p53 protein, slide along DNA. Characteristics of the 'molecular sled' in its milieu (virion, nucleus) have implications for how proteins in the nucleus of cells interact and imply a new form of biochemistry, one-dimensional biochemistry. PMID- 26831566 TI - Icaritin requires Phosphatidylinositol 3 kinase (PI3K)/Akt signaling to counteract skeletal muscle atrophy following mechanical unloading. AB - Counteracting muscle atrophy induced by mechanical unloading/inactivity is of great clinical need and challenge. A therapeutic agent that could counteract muscle atrophy following mechanical unloading in safety is desired. This study showed that natural product Icaritin (ICT) could increase the phosphorylation level of Phosphatidylinositol 3 kinase (PI3K) at p110 catalytic subunit and promote PI3K/Akt signaling markers in C2C12 cells. This study further showed that the high dose ICT treatment could significantly attenuate the decreases in the phosphorylation level of PI3K at p110 catalytic subunit and its downstream markers related to protein synthesis, and inhibit the increases in protein degradation markers at mRNA and protein levels in rat soleus muscle following 28 day hindlimb unloading. In addition, the decreases in soleus muscle mass, muscle fiber cross-sectional area, twitch force, specific force, contraction time and half relaxation time could be significantly attenuated by the high dose ICT treatment. The low dose ICT treatment could moderately attenuate the above changes induced by unloading. Wortmannin, a specific inhibitor of PI3K at p110 catalytic subunit, could abolish the above effects of ICT in vitro and in vivo, indicating that PI3K/Akt signaling could be required by ICT to counteract skeletal muscle atrophy following mechanical unloading. PMID- 26831567 TI - Inhibition of lysosomal protease cathepsin D reduces renal fibrosis in murine chronic kidney disease. AB - During chronic kidney disease (CKD) there is a dysregulation of extracellular matrix (ECM) homeostasis leading to renal fibrosis. Lysosomal proteases such as cathepsins (Cts) regulate this process in other organs, however, their role in CKD is still unknown. Here we describe a novel role for cathepsins in CKD. CtsD and B were located in distal and proximal tubular cells respectively in human disease. Administration of CtsD (Pepstatin A) but not B inhibitor (Ca074-Me), in two mouse CKD models, UUO and chronic ischemia reperfusion injury, led to a reduction in fibrosis. No changes in collagen transcription or myofibroblasts numbers were observed. Pepstatin A administration resulted in increased extracellular urokinase and collagen degradation. In vitro and in vivo administration of chloroquine, an endo/lysosomal inhibitor, mimicked Pepstatin A effect on renal fibrosis. Therefore, we propose a mechanism by which CtsD inhibition leads to increased collagenolytic activity due to an impairment in lysosomal recycling. This results in increased extracellular activity of enzymes such as urokinase, triggering a proteolytic cascade, which culminates in more ECM degradation. Taken together these results suggest that inhibition of lysosomal proteases, such as CtsD, could be a new therapeutic approach to reduce renal fibrosis and slow progression of CKD. PMID- 26831568 TI - In vivo kinematics of a unique posterior-stabilized knee implant during a stepping exercise. AB - BACKGROUND: Stair-stepping motion is important in daily living, similar to gait. Knee prostheses need to have even more superior performance and stability in stair-stepping motion than in gait. The purpose of this analysis was to estimate in vivo knee motion in stair stepping and determine if this unique knee prosthesis function as designed. METHODS: A total of 20 patients with Bi-Surface posterior-stabilizing (PS) implants were assessed. The Bi-Surface PS knee is a posterior-cruciate substitute prosthesis with a unique ball-and-socket joint in the mid-posterior portion of the femoral and tibial components. Patients were examined during stair-stepping motion using a 2-dimensional to 3-dimensional registration technique. RESULTS: The kinematic pattern in step up was a medial pivot, in which the level of anteroposterior translation was very small. In step down, the kinematic pattern was neither a pivot shift nor a rollback. From minimum to maximum flexion, anterior femoral translation occurred slightly. CONCLUSIONS: In this study, this unique implant had good joint stability during stair stepping. The joint's stability during stair stepping was affected by the design of the femorotibial joint rather than post/cam engagement or the ball-and socket joint. PMID- 26831569 TI - Impact of an Antimicrobial Stewardship Program on Patient Safety in Veterans Prescribed Vancomycin. AB - PURPOSE: This study aimed to determine the safety impact of an antimicrobial stewardship program (ASP) on vancomycin-associated nephrotoxicity and to examine risk factors contributing to the development of toxicity. METHODS: This was a retrospective chart review of data from 453 veterans receiving vancomycin in the VA Western New York Healthcare System between October 2006 and July 2014. Nephrotoxicity was defined as an increase in serum creatinine of >= 0.5 mg/dL or by 50% of baseline for 2 consecutive days. FINDINGS: Patients receiving vancomycin after the implementation of the ASP were less likely to develop nephrotoxicity (odds ratio [OR] = 2.06; 95% CI, 1.02-4.28). Nephrotoxicity occurred in 6.84% of patients from the pre-ASP cohort and in 3.75% of patients after the implementation of the ASP. Predictors of nephrotoxicity included hospital service (surgical service, OR = 2.29; 95% CI, 1.13-4.64), elevated maximum trough concentration (unit OR = 1.15; 95% CI, 1.10-1.20), and concurrent piperacillin/tazobactam therapy (OR = 3.21; 95% CI, 1.43-7.96). The number of vancomycin trough concentration measurements per patient did not vary between the pre-ASP and ASP groups. IMPLICATIONS: ASPs represent an important aspect of a patient-safety initiative in order to reduce vancomycin-associated nephrotoxicity. Concurrent piperacillin/tazobactam therapy, surgical service, and elevated maximum trough concentration were risk factors for nephrotoxicity. PMID- 26831570 TI - Prebiotic NH3 Formation: Insights from Simulations. AB - Simulations of prebiotic NH3 synthesis from NO3- and NO2- on pyrite surfaces under hydrothermal conditions are reported. Ab initio metadynamics calculations have successfully explored the full reaction path which explains earlier experimental observations. We have found that the reaction mechanism can be constructed from stepwise single atom transfers which are compatible with the expected reaction time scales. The roles of the hot-pressurized water and of the pyrite surfaces have been addressed. The mechanistic picture that emerged from the simulations strengthens the theory of chemoautotrophic origin of life by providing plausible reaction pathways for the formation of ammonia within the iron-sulfur-world scenario. PMID- 26831571 TI - Changing Patient Position Can Eliminate Arrhythmias Developing During Extracorporeal Shockwave Lithotripsy. AB - INTRODUCTION: Extracorporeal shockwave lithotripsy (SWL) has a low complication rate. While serious complications are rare, cardiac arrhythmias, such as ventricular tachycardia, may occur. The etiology of these arrhythmias is poorly understood, but it appears to be due to stimulation of the heart by the shock waves. OBJECTIVE: This study examines the effect of rotating the patient 15 degrees to 20 degrees when an arrhythmia occurs. METHODS: Eight hundred nineteen patients were prospectively evaluated for arrhythmias during SWL. The initial patient position was dependent on the location of the stone and the body mass index (BMI) of the patient. If a sustained arrhythmia developed, treatment was withheld for 2 minutes and then recommenced. If the patient developed an arrhythmia again, the patient was rotated 15 degrees -20 degrees away from the original position and treatment recommenced. RESULTS: Twenty patients developed significant arrhythmias during SWL. Arrhythmias occurred more frequently in patients with a lower BMI (p < 0.01), of younger age (p = 0.01), and with right sided stones (p = 0.035). After the first rotation, 11 patients had no further arrhythmias, and 4 patients had a reduction of their arrhythmia to unsustained minor arrhythmias that did not require cessation of the treatment. The remaining five patients required a second repositioning. Three of these patients required gated SWL to abolish the arrhythmia. CONCLUSION: Changing the position of the patient by rotating the patient by 15 to 20 degrees can eliminate arrhythmias that develop during SWL. PMID- 26831572 TI - Macular pigmentation of uncertain aetiology revisited: two case reports and a proposed algorithm for clinical classification. AB - Ashy dermatosis, erythema dyschromicum perstans, lichen planus pigmentosus and idiopathic eruptive macular pigmentation are various types of acquired macular hyperpigmentation disorders of the skin described in literature. However, a global consensus on the definitions of these entities is lacking. We report two cases of acquired macular (hyper)pigmentation of uncertain aetiology diagnosed as ashy dermatosis and attempt to clarify the various confusing nosologies based on existing literature. We infer that acquired small and large macular pigmentation of uncertain aetiology should be considered separate from that associated with lichen planus. We also propose a diagnostic algorithm for patients with acquired macular hyperpigmentation. PMID- 26831573 TI - Facile Five-Step Heteroepitaxial Growth of GaAs Nanowires on Silicon Substrates and the Twin Formation Mechanism. AB - Monolithic integration of III-V semiconductors with Si has been pursued for some time in the semiconductor industry. However, the mismatch of lattice constants and thermal expansion coefficients represents a large technological challenge for the heteroepitaxial growth. Nanowires, due to their small lateral dimension, can relieve strain and mitigate dislocation formation to allow single-crystal III-V materials to be grown on Si. Here, we report a facile five-step heteroepitaxial growth of GaAs nanowires on Si using selective area growth (SAG) in metalorganic chemical vapor deposition, and we further report an in-depth study on the twin formation mechanism. Rotational twin defects were observed in the nanowire structures and showed strong dependence on the growth condition and nanowire size. We adopt a model of faceted growth to demonstrate the formation of twins during growth, which is well supported by both a transmission electron microscopy study and simulation based on nucleation energetics. Our study has led to twin free segments in the length up to 80 nm, a significant improvement compared to previous work using SAG. The achievements may open up opportunities for future functional III-V-on-Si heterostructure devices. PMID- 26831574 TI - Sustainable biorefining in wastewater by engineered extreme alkaliphile Bacillus marmarensis. AB - Contamination susceptibility, water usage, and inability to utilize 5-carbon sugars and disaccharides are among the major obstacles in industrialization of sustainable biorefining. Extremophilic thermophiles and acidophiles are being researched to combat these problems, but organisms which answer all the above problems have yet to emerge. Here, we present engineering of the unexplored, extreme alkaliphile Bacillus marmarensis as a platform for new bioprocesses which meet all these challenges. With a newly developed transformation protocol and genetic tools, along with optimized RBSs and antisense RNA, we engineered B. marmarensis to produce ethanol at titers of 38 g/l and 65% yields from glucose in unsterilized media. Furthermore, ethanol titers and yields of 12 g/l and 50%, respectively, were produced from cellobiose and xylose in unsterilized seawater and algal-contaminated wastewater. As such, B. marmarensis presents a promising approach for the contamination-resistant biorefining of a wide range of carbohydrates in unsterilized, non-potable seawater. PMID- 26831575 TI - Role of albumin in diseases associated with severe systemic inflammation: Pathophysiologic and clinical evidence in sepsis and in decompensated cirrhosis. AB - The metabolism of albumin in inflammatory states such as sepsis or major surgery is complex and still not well characterized. Nevertheless, in inflammatory states, albumin synthesis has been observed to increase. By contrast, in decompensated cirrhosis, a disease characterized by systemic inflammation, albumin synthesis by the liver may decrease to 30% to 50% of normal values. Furthermore, in these conditions, there are high capillary leakage and altered albumin kinetics. The discussion regarding the effect of exogenous albumin administration on intravascular volume in inflammatory states should therefore address albumin turnover. To add complexity to our understanding of the effects of albumin, there are many data indicating that the therapeutic action of albumin is mediated not only through the impact on plasma volume expansion but also through a modulatory effect on inflammation and oxidative stress. All these characteristics are relevant to diseases associated with systemic inflammation including sepsis and decompensated cirrhosis. PMID- 26831576 TI - Noninvasive ventilation in acute respiratory distress syndrome: Primum non nocere. PMID- 26831577 TI - Computational design of peptide-Au cluster probe for sensitive detection of alpha(IIb)beta3 integrin. AB - We have designed a novel peptide-Au cluster probe to specifically bind to alphaIIbbeta3 integrin. As indicated by molecular dynamics (MD) simulations, the binding mode of the native ligand of alphaIIbbeta3 integrin, gammaC peptide, can be realized by the designed probe. More importantly, the peptide-Au probe can provide multiple coating peptides to form additional salt bridges with protein, and the binding stability of the probe is comparable to the native ligand. The designed probe was then successfully synthesized. The specific binding in a cellular environment was validated by colocalization analysis of confocal microscopy. In addition, the binding affinity was confirmed by atomic force microscopy (AFM) based single molecule force spectroscopy. Our results suggest the combination of computational design and experimental verification can be a useful strategy for the development of nanoprobes. PMID- 26831579 TI - How to efficiently characterize special effect coatings. AB - Coatings and plastics that contain special effect pigments show angular-dependent reflection characteristics. Interference pigments, for instance, exhibit a color impression ("appearance") that changes with the directions of illumination and observation. It is currently an open question how the appearance of such coatings can be best characterized without extensive measurements of the spectral radiance factor. In this paper, a simple and efficient approach is presented on how to characterize the appearance of surfaces composed of metallic and interference pigments. Based on the rotational symmetry of the pigment distribution around the surface normal, it is demonstrated how the appearance at any configuration of illumination and observation can be estimated from a set of in-plane measurements. For practical applications, it is shown that a rather small number of geometries (e.g., 10) are sufficient. The presented methodology is an alternative to a recent principal components analysis-based procedure and offers the advantage of being based directly on an extensible physical model while having at least the same prediction accuracy. PMID- 26831580 TI - Optimal configuration of static polarization imagers for target detection. AB - We determine the set of analysis states of a static Stokes imager that maximizes target detection performance for the least favorable target-background polarimetric configuration. By using a minimax approach, we demonstrate that the optimal choice consists of four analysis states forming a regular tetrahedron in the Poincare sphere. We also show that the value of the contrast in the best of the four Stokes channels is, in the worst case, equal to one third of that provided by a fully adaptive polarimetric imager. Static Stokes imagers thus constitute an attractive solution in applications where limited loss of discrimination ability can be tolerated. PMID- 26831578 TI - Combined local and systemic immunization is essential for durable T-cell mediated heterosubtypic immunity against influenza A virus. AB - The threat from unpredictable influenza virus pandemics necessitates the development of a new type of influenza vaccine. Since the internal proteins are highly conserved, induction of T cells targeting these antigens may provide the solution. Indeed, adenoviral (Ad) vectors expressing flu nucleoprotein have previously been found to induce short-term protection in mice. In this study we confirm that systemic (subcutaneous (s.c.) immunization rapidly induced heterosubtypic protection predominantly mediated by CD8 T cells, but within three months clinical protection completely disappeared. Local (intranasal (i.n.)) immunization elicited delayed, but more lasting protection despite relatively inefficient immunization. However, by far, the most robust protection was induced by simultaneous, combined (i.n. + s.c.) vaccination, and, notably, in this case clinical protection lasted at least 8 months without showing any evidence of fading. Interestingly, the superior ability of the latter group to resist reinfection correlated with a higher number of antigen-specific CD8 T cells in the spleen. Thus, detailed analysis of the underlying CD8 T cell responses highlights the importance of T cells already positioned in the lungs prior to challenge, but at the same time underscores an important back-up role for circulating antigen-specific cells with the capacity to expand and infiltrate the infected lungs. PMID- 26831581 TI - Evaluating color texture descriptors under large variations of controlled lighting conditions. AB - The recognition of color texture under varying lighting conditions remains an open issue. Several features have been proposed for this purpose, ranging from traditional statistical descriptors to features extracted with neural networks. Still, it is not completely clear under what circumstances a feature performs better than others. In this paper, we report an extensive comparison of old and new texture features, with and without a color normalization step, with a particular focus on how these features are affected by small and large variations in the lighting conditions. The evaluation is performed on a new texture database, which includes 68 samples of raw food acquired under 46 conditions that present single and combined variations of light color, direction, and intensity. The database allows us to systematically investigate the robustness of texture descriptors across large variations of imaging conditions. PMID- 26831582 TI - Energy-driven path search for Termite Retinex. AB - The human color sensation depends on the local and global spatial arrangements of the colors in the scene. Emulating this dependence requires the exploration of the image in search of a white reference. The algorithm Termite Retinex explores the image by a set of paths resembling traces of a swarm of termites. Starting from this approach, we develop a novel spatial exploration scheme where the termite paths are local minimums of an energy function, which depend on the image visual content. The energy is designed to favor the visitation of regions containing information relevant to the color sensation while minimizing the coverage of less essential regions. This exploration method contributes to the investigation of the spatial properties of the color sensation and, to the best of our knowledge, is the first model relying on mathematical global conditions for the Retinex paths. The experiments show that the estimation of the color sensation obtained by means of the proposed spatial sampling is a valid alternative to the one based on Termite Retinex. PMID- 26831583 TI - Components of purity of a three-dimensional polarization state. AB - The degree of polarimetric purity of a three-dimensional (3D) polarization state is a measure of the closeness to a pure state and can be expressed as a weighted quadratic average of two indices of polarimetric purity, invariant with respect to unitary transformations and defined in terms of the relative weights of certain incoherent components of the state. An alternative view of the polarimetric purity is formulated in terms of three contributions, namely, the degree of directionality, the degree of linear polarization, and the degree of circular polarization. While the indices of polarimetric purity give complete information on the structure of randomness but are insensitive to other attributes of the state of polarization, the three components of purity are invariant under orthogonal transformations (rotations in the real space) and provide a meaningful framework for the representation of 3D polarization states in terms of quantities that are intrinsic for each given state. PMID- 26831584 TI - Internal structure of an optical null Ronchi grating test for a plano-parabolic lens. AB - In this work we use geometrical optics and the caustic touching theorem, introduced by Berry, to describe the internal structure of the null Ronchi grating for a plano-parabolic lens illuminated by a point light source placed on the optical axis. The aim of this work is to explain the role of the caustic region in the process of morphology change between image and object in computing the null Ronchi grating. To this end, we obtain the analytic expression of the null Ronchi grating, and after that we deeply study the change in morphology between a single straight fringe image at the Ronchigram and the multiple curve rulings that can generate it (one open and one closed). We analyze exactly how multiple rulings generate the same straight image fringe, or how an entire ruling collapses into a single point image. For this analysis, we take different observation planes at different positions with respect to the caustic region. Finally, we characterize this topological change as one of two possible kinds depending on the relative position between the observation plane and the caustic region. PMID- 26831585 TI - Invariant quantities of a Mueller matrix under rotation and retarder transformations. AB - Mueller matrices are defined with respect to appropriate Cartesian reference frames for the representation of the states of polarization of the input and output electromagnetic probe beams. The polarimetric quantities that are invariant under rotations of the said reference frames about the respective directions of propagation (rotation transformations) provide particularly interesting physical information. Moreover, certain properties are also invariant with respect to the action of birefringent devices located on both sides of the medium under consideration (retarder transformations). The polarimetric properties that remain invariant under rotation and retarder transformations are calculated from any given Mueller matrix and are then analyzed and interpreted, providing significant parameterizations of Mueller matrices in terms of meaningful physical quantities. PMID- 26831586 TI - Extremum-seeking control of the beam pattern of a reconfigurable holographic metamaterial antenna. AB - Robust, continuous, and software-defined beam pattern control of holographic metamaterial antennas is necessary to realize the potential of these low-power consumption, thin, lightweight, inexpensive antennas for consumer usage of satellite communication. We present a complete feedback control approach that enables adaptive control of the radiation pattern for the electronically scanned metamaterial antenna that is robust to measurement noise and is able to continuously optimize performance throughout changing environmental conditions and antenna characteristics. The physical size, weight, and cost advantages of the metamaterial antenna make it an attractive technology when paired with robust and adaptive on-board software strategies to optimize antenna performance and self-tune for various environmental conditions. PMID- 26831587 TI - Quantitative analysis of fringe visibility in grating-based x-ray phase-contrast imaging. AB - The newly developed x-ray differential phase-contrast imaging technique has attracted increasing research interest. In this study, we quantitatively analyze the fringe visibility obtained in differential phase-contrast imaging. Numerical results of the visibility for polychromatic x rays with different structure heights of absorption gratings are shown and discussed. Furthermore, the fringe visibility of the nonabsorption grating approach is calculated, and based on the results, we conclude that this approach can potentially be applied for higher x ray photon energies. These analytic results will be useful for designing a differential phase-contrast imaging system for different applications. PMID- 26831588 TI - Automatic detection of microaneurysms in diabetic retinopathy fundus images using the L*a*b color space. AB - We develop an automated image processing system for detecting microaneurysm (MA) in diabetic patients. Diabetic retinopathy is one of the main causes of preventable blindness in working age diabetic people with the presence of an MA being one of the first signs. We transform the eye fundus images to the L*a*b* color space in order to separately process the L* and a* channels, looking for MAs in each of them. We then fuse the results, and last send the MA candidates to a k-nearest neighbors classifier for final assessment. The performance of the method, measured against 50 images with an ophthalmologist's hand-drawn ground truth, shows high sensitivity (100%) and accuracy (84%), and running times around 10 s. This kind of automatic image processing application is important in order to reduce the burden on the public health system associated with the diagnosis of diabetic retinopathy given the high number of potential patients that need periodic screening. PMID- 26831589 TI - Hessian-LoG filtering for enhancement and detection of photoreceptor cells in adaptive optics retinal images. AB - Automated analysis of retinal images plays a vital role in the examination, diagnosis, and prognosis of healthy and pathological retinas. Retinal disorders and the associated visual loss can be interpreted via quantitative correlations, based on measurements of photoreceptor loss. Therefore, it is important to develop reliable tools for identification of photoreceptor cells. In this paper, an automated algorithm is proposed, based on the use of the Hessian-Laplacian of Gaussian filter, which allows enhancement and detection of photoreceptor cells. The performance of the proposed technique is evaluated on both synthetic and high resolution retinal images, in terms of packing density. The results on the synthetic data were compared against ground truth as well as cone counts obtained by the Li and Roorda algorithm. For the synthetic datasets, our method showed an average detection accuracy of 98.8%, compared to 93.9% for the Li and Roorda approach. The packing density estimates calculated on the retinal datasets were validated against manual counts and the results obtained by a proprietary software from Imagine Eyes and the Li and Roorda algorithm. Among the tested methods, the proposed approach showed the closest agreement with manual counting. PMID- 26831590 TI - Impact of wave polarization on long-range intensity correlations in a disordered medium. AB - We present a theory of long-range intensity correlations in phase-coherent transport of polarized light through a disordered medium. Diagrammatic calculations of the intensity correlation function are performed beyond the scalar wave approximation. The correlations between the cross-polarized fields are shown to result in the dependence of mesoscopic intensity fluctuations on the polarization of the incident light. The intensity correlation function is represented as a sum of the contributions from the scalar mode and the basic modes of circular and linear polarization. The calculations, as applied to media with large scattering inhomogeneities, are carried out for diffusive transport and for small-angle multiple scattering of light. Each polarization contribution to the variance of relative transmission fluctuations is shown not to be a self averaging quantity and tends to a nonvanishing value as the sample thickness increases. This value is proportional to the length of polarization decay in the medium and can be measured by varying the initial polarization of light. PMID- 26831591 TI - Co-design of an in-line holographic microscope with enhanced axial resolution: selective filtering digital holography. AB - Common-path digital in-line holography is considered as a valuable 3D diagnostic technique for a wide range of applications. This configuration is cost effective and relatively immune to variation in the experimental environment. Nevertheless, due to its common-path geometry, the signal-to-noise ratio of the acquired hologram is weak as most of the detector (i.e., CCD/CMOS sensor) dynamics are occupied by the reference field signal, whose energy is orders of magnitude higher than the field scattered by the imaged object. As it is intrinsically impossible to modify the ratio of energy of reference to the object field, we propose a co-design approach (optics/data processing) to tackle this issue. The reference to the object field ratio is adjusted by adding a 4-f device to a conventional in-line holographic setup, making it possible to reduce the weight of the reference field while keeping the object field almost constant. Theoretical analysis of the Cramer-Rao lower bounds of the corresponding imaging model illustrates the advantages of this approach. These lower bounds can be asymptotically reached using a parametric inverse problem reconstruction. This implementation results in a 60% gain in axial localization accuracy (for 100 MUm diameter spherical objects) compared to a classical in-line holography setup. PMID- 26831592 TI - Designing illumination lenses and mirrors by the numerical solution of Monge Ampere equations: publisher's note. AB - Production errors in the published version of J. Opt. Soc. Am. A32, 2227 (2015)JOAOD60740-323210.1364/JOSAA.32.002227 are reported in this note. The errors involve the rendering and content of the mathematics and some of the references and their citations. PMID- 26831593 TI - Coherence properties of the electric field generated by an incoherent source of currents distributed on the surface of a sphere. AB - We derive analytical expressions of the cross-spectral density of the electric field arising from an incoherent source whose current density is located on the surface of a sphere. Our approach is based on the series expansion in terms of vector spherical harmonics of the electric field generated by the aforementioned current distribution. We analyze in detail the spectrum, the degree of coherence, and the degree of polarization of the electric field for all regions in space (from the near field to the far field). The relationship of the high-order harmonics to the coherence properties is discussed. The spectrum turns out to be isotropic and it is different from that of the source. We found that the degree of coherence and degree of polarization are strongly influenced by the size of the source. We show the appearance of special features: a zone with a high degree of coherence in the near field for a subwavelength source, the radial degree of coherence is nearly constant in an extended region where two radial points belong to the far field, and a particular radial distance for which the degree of polarization vanishes (3D unpolarized light). PMID- 26831594 TI - Single all-optical platform for measurement of twist and transverse stress using polarization modulation in distinct dual-mode fiber placed in a Sagnac loop. AB - We report here the experimental demonstration of measurement of both twist and transverse stress using polarization modulation in a single all-fiber circuit consisting of a single-mode fiber (SMF)/dual-mode fiber (DMF) in a Sagnac interferometer (SI) loop. The SMF-SI prototype setup is seen to be suitable for precise measurement of twist over a broad range of +/-50 degrees and transverse stress up to 5 N with a sensitivity as high as 2.85*10(6) pW/ degrees and 2.08*10(7) pW/N, respectively. It is envisaged that nearly ideal operation for twist measurement can be achieved by appropriately selecting the operating domain (pretwisted Sagnac loop for practical realization of the device) and required magnitude of applied transverse stress (weight yielding maximum sensitivity). Unlike SMF-SI, a DMF assisted SI exhibits asymmetric transmittance yielding a peak shift (~45 degrees ) in addition to falling/rising peak amplitude of effective power(~20 MUW). This key characteristic is further utilized for tunable measurement of torsion (unidirectional from -70 degrees to 40 degrees ) while keeping the sensitivity fixed. This research problem is then analyzed on the avenue of theoretical consideration and using classical polarization optics; we have derived the Jones birefringence matrix that accurately describes the transmission behavior of the configured fiber circuit (SMF-SI and DMF-SI) for each of the three cases, namely, transverse stress, twist, and both twist and transverse stress. Series of experimental measurements for various conditions of induced birefringence (linear/circular) were performed at length, and the results were compared with those determined theoretically towards configuring a twist and stress measuring device. The study provides an understanding of the underlying physics of dual-mode interference in a Sagnac configuration experiencing linear and circular birefringence. PMID- 26831595 TI - Does correlated color temperature affect the ability of humans to identify veins? AB - In the present study we provide empirical evidence and demonstrate statistically that white illumination settings can affect the human ability to identify veins in the inner hand vasculature. A special light-emitting diode lamp with high color rendering index (CRI 84-95) was developed and the effect of correlated color temperature was evaluated, in the range between 2600 and 5700 K at an illuminance of 40+/-9 lx on the ability of adult humans to identify veins. It is shown that the ability to identify veins can, on average, be increased up to 24% when white illumination settings that do not resemble incandescent light are applied. The illuminance reported together with the effect of white illumination settings on direct visual perception of biosamples are relevant for clinical investigations during the night. PMID- 26831596 TI - Celebrating the new and old: editorial. AB - New editor-in-chief P. Scott Carney makes some opening remarks and comments on special OSA Centennial activities this year at JOSA A. PMID- 26831597 TI - Weight control practices of Division I National Collegiate Athletic Association athletes. AB - OBJECTIVES: Altering body weight can have substantial effects on an athlete's performance and well-being. Limited information is available describing the weight control practices of Division I National Collegiate Athletic Association (NCAA) athletes. METHODS: Weight control practices data from 188 (138 male and 50 female; 18-23 y) Division I NCAA athletes were analyzed as a part of this cross sectional, retrospective study. Participants completed questionnaires on weight control practices and weight control nutrition knowledge at the end of their season and were classified into weight-sensitive and less weight-sensitive sports. RESULTS: A higher proportion of females attempted to lose weight than males among less weight-sensitive sports (61% vs. 22%, chi-square = 15.8, p < 0.001). However, the prevalence of weight loss attempts was not different between females and males among weight-sensitive sports (50% vs. 60%, chi-square = 0.5, p = 0.479). The prevalence of weight gain attempts differed by gender for less weight-sensitive sports (65% vs. 4% for males and females, chi-square = 33.5, p < 0.001) but not weight-sensitive sports (24% vs. 9% for males and females, chi square = 2.1, p = 0.146). Weight control knowledge did not differ between participants attempting versus not attempting to lose weight (Mann-Whitney U = 3340, z = -1.37, p = 0.17). Common maladaptive behaviors used to lose weight included skipping meals and exercising more than usual. CONCLUSION: Weight loss attempts are common among Division I NCAA athletes, and the differences between males and females may be more pronounced among less weight-sensitive sports. Weight gain attempts are more common in select male sports. PMID- 26831598 TI - Defects-assisted ferromagnetism due to bound magnetic polarons in Ce into Fe, Co:ZnO nanoparticles and first-principle calculations. AB - Zn0.94TM0.03Ce0.03O [Zn0.94Fe0.03Ce0.03O (ZFCeO) and Zn0.94Co0.03Ce0.03O (ZCCeO)] nanoparticles were synthesized by a sol-gel process. Elemental analysis of these nanoparticles detects the weight percentage of Zn, Co, Fe, Ce and O in each sample. The Rietveld refinement of the X-ray diffraction pattern obtains the occupancy of dopant atoms, Wurtzite ZnO structure, crystallinity and lattice deformation with doping. The Ce doping into ZFO and ZCO form nanoparticles than nanorods was observed in pure ZnO, ZFO and ZCO samples that described due to chemical and ionic behavior of Ce, Fe, Co and Zn ions. The Raman active modes have peak broadening, intensity changes and peak shifts with metal doping that induces lattice defects. Photoluminescence spectra show blue-shifts at near-band edges and defects that influence broad visible emission with Ce doping. An enhancement in ferromagnetism in the magnetic hysteresis at 5 K is measured. The zero-field cooling and field cooling at H = 500 Oe and T = 300-5 K could confirm antiferromagnetic interactions mediated by defect carriers. The bound magnetic polaron at defect sites is responsible for the observed ferromagnetism. The ac magnetic susceptibility measurements determine the antiferromagnetic to ferromagnetic transition with some magnetic clustered growth in the samples and reveal a frequency independent peak that shows the Neel temperature. Weak room temperature ferromagnetism and optical quenching in ZFCeO are described by valance states of Fe and Ce ions, respectively. Using first-principle calculations, we studied the occupancy of Ce (replacing Zn atoms) in the Wurtzite structure. PMID- 26831599 TI - Molecular mechanisms of ionic liquid cytotoxicity probed by an integrated experimental and computational approach. AB - Ionic liquids (ILs) are salts that remain liquid down to low temperatures, and sometimes well below room temperature. ILs have been called "green solvents" because of their extraordinarily low vapor pressure and excellent solvation power, but ecotoxicology studies have shown that some ILs exhibit greater toxicity than traditional solvents. A fundamental understanding of the molecular mechanisms responsible for IL toxicity remains elusive. Here we show that one mode of IL toxicity on unicellular organisms is driven by swelling of the cell membrane. Cytotoxicity assays, confocal laser scanning microscopy, and molecular simulations reveal that IL cations nucleate morphological defects in the microbial cell membrane at concentrations near the half maximal effective concentration (EC50) of several microorganisms. Cytotoxicity increases with increasing alkyl chain length of the cation due to the ability of the longer alkyl chain to more easily embed in, and ultimately disrupt, the cell membrane. PMID- 26831600 TI - CO2 insufflation or warm water infusion for unsedated colonoscopy: A randomized controlled trial in patients with chronic constipation in China. PMID- 26831601 TI - The implications of oxidative stress and antioxidant therapies in Inflammatory Bowel Disease: Clinical aspects and animal models. AB - Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder characterized by alternating phases of clinical relapse and remission. The etiology of IBD remains largely unknown, although a combination of patient's immune response, genetics, microbiome, and environment plays an important role in disturbing intestinal homeostasis, leading to development and perpetuation of the inflammatory cascade in IBD. As chronic intestinal inflammation is associated with the formation of reactive oxygen and reactive nitrogen species (ROS and RNS), oxidative and nitrosative stress has been proposed as one of the major contributing factor in the IBD development. Substantial evidence suggests that IBD is associated with an imbalance between increased ROS and decreased antioxidant activity, which may explain, at least in part, many of the clinical pathophysiological features of both CD and UC patients. Hereby, we review the presently known oxidant and antioxidant mechanisms involved in IBD-specific events, the animal models used to determine these specific features, and also the antioxidant therapies proposed in IBD patients. PMID- 26831603 TI - The prognostic value of UHRF-1 and p53 in gastric cancer. AB - BACKGROUND/AIMS: This study aimed to examine whether UHRF-1 and p53 overexpression is a prognostic marker for gastric cancer. PATIENTS AND METHODS: Sixty-four patients with gastric cancer (study group) and 23 patients with gastritis (control group) were evaluated. Immunohistochemistry was used to examine expression of UHRF-1 and p53 in gastric cancers and a control group diagnosed with gastritis. RESULTS: The median age was 63 years (18-83 years) in the study group. UHRF-1 was positive in 15 (23%) patients with gastric cancer and fi ve (21.7%) patients with gastritis (P = 0.559). UHRF1 expression level in gastric cancer is more powerful than in gastritis (P = 0.046). Thirty-seven (61%) patients with gastric cancer and only one patient with gastritis were p53 positive (P < 0.001). After a median follow-up of 12 months (1-110), the 2-year overall survival rates were 55% and 30% in negative and positive p53, respectively (P = 0.084). Also, the 2-year overall survival rates were 45% and 53% in negative and positive UHRF-1, respectively (P = 0.132). CONCLUSION: According to this study, UHRF-1 and p53 were not prognostic factors for gastric cancer, whereas they may have a diagnostic value for differentiating between gastric cancer and gastritis. PMID- 26831602 TI - Carbon dioxide insufflation or warm-water infusion for unsedated colonoscopy: A randomized controlled trial in patients with chronic constipation in China. AB - AIMS: The effect of carbon dioxide (CO2) insufflation and warm-water infusion during colonoscopy on patients with chronic constipation remains unknown. We evaluated CO 2 insufflation and warm-water irrigation versus air insufflation in unsedated patients with chronic constipation in China. PATIENTS AND METHODS: This randomized, single-center, controlled trial enrolled 287 consecutive patients, from January 2014 to January 2015, who underwent colonoscopy for chronic constipation. Patients were randomized to CO2 insufflation, warm-water irrigation and air insufflation colonoscopy insertion phase groups. Pain scores were assessed by the visual analog scale (VAS). The primary outcome was real-time maximum insertion pain, recorded by an unblinded nurse assistant. At discharge, the recalled maximum insertion pain was recorded. Meanwhile, patients were requested to select the VAS at 0, 10, 30, and 60 min after the procedure. In addition, cecal intubation and withdrawal time, total procedure time, and adjunct measures were recorded. RESULTS: A total of 287 patients were randomized. The correlation between real-time and recalled maximum insertion pain ((Pearson coefficient r = 0.929; P < 0.0001) confirmed internal validation of the primary outcome. The mean real-time maximum pain scores during insertion 2.9 +/- 2.1 for CO2, 2.7 +/- 1.9 for water achieved a significantly lower pain score compared with air (5.7 +/- 2.5) group (air vs CO2 P < 0.001; air vs water P < 0.001). However, no significant pain score differences were found between the patients in the CO2 and water groups (CO2 vs water, P = 0.0535). P values in painless colonoscopy and only discomfort colonoscopy (pain 1-2) were, respectively, 6 (6.4%) and 8 (8.5%) for air; 17 (17.7%) and 29 (30.2%) for CO2; 16 (16.5%) and 31 (31.9%) for water. At 0, 10, 30, and 60 min postprocedure, pain scores showed in the CO2 and water groups had significantly reduced than in air group. Insertion time was significantly different between air (10.6 +/- 2.5) and CO2 ( 7.2 +/- 1.4) (air vs CO2 P < 0.001), air and water (6.9 +/- 1.3) (air vs water P < 0.001). However, CO2 and was not significantly different in cecum-intubated time (CO2 vs water, P = 0.404). CO2 and water group in extubation time were significantly different, respectively, CO2 (7.9 +/- 1.1) and water (8.0 +/- 1.1) (CO2 vs water, P = 0.707). CO2 or water group required less implementation of adjunct measures and more willingness to repeat the procedure. CONCLUSIONS: Compared with air, the CO2 or water-aided method reduced real-time maximum pain and cecum-intubated time for chronic constipated patients in unsedated colonoscopy. The CO2 insufflation or warm-water irrigation may be a simple and inexpensive way to reduce discomfort in unsedated patients with constipation. This study demonstrated an advantage of using CO2 insufflation and warm-water irrigation during colonoscopy in unsedated constipated patients in China. PMID- 26831604 TI - MicroRNA-155-enhanced autophagy in human gastric epithelial cell in response to Helicobacter pylori. AB - BACKGROUND/AIM: MicroRNAs (miRNAs) are a class of small noncoding RNAs acting as posttranscriptional gene expression regulators in many physiological and pathological conditions. MiR-155 is one kind of miRNAs that plays an important role in causing various diseases. However, the precise molecular mechanism of the ectopic expression of miR-155 in Helicobacter pylori infection remains poorly understood. Autophagy has recently been identified as an effective way to control the intracellular bacterium survival. In the present study, we demonstrate a novel role of miR-155 in regulating the autophagy-mediated anti-H. pylori response. PATIENTS AND METHODS: Totally 86 H. pylori-positive patients together with 10 H. pylori-negative, healthy control subjects were included in the study. Correlation between immunohistochemical grades and miR-155 expression were determined. Molecular mechanism of miR-155 on regulation of autophagy and elimination of intracellular H. pylori were determined using the GES-1 cell model. RESULTS: We found that overexpression of miR-155 by transfecting miR-155 mimics could significantly decrease the survival of intracellular H. pylori, and this process was through induction of autophagy. Furthermore, there was a significant correlation between miR-155 and immunohistochemical grades in H. pylori-positive patients, and miR-155 expression were decreased in the intestinal metaplasia group. CONCLUSIONS: The results have indicated that the miR-155 expression level plays a key role in immunity response against H. pylori and this might provide potential targets for the future treatment of H. pylori-related diseases. PMID- 26831605 TI - Antiviral efficacy of entecavir versus entecavir plus adefovir for hepatitis B virus rtA181V/T mutants alone. AB - BACKGROUND/AIMS: Hepatitis B virus (HBV) rtA181V/T mutants developed by long-term nucleos(t) ide analogue therapy are known to present cross-resistance for other nucleos (t) ide analogues, except entecavir (ETV). Some studies reported that HBV rtA181V/T mutants could induce cross-resistance to ETV and showed incomplete response as well as persistence of HBV DNA, despite rescue therapy by ETV. This study aimed to investigate the antiviral efficacy of ETV monotherapy and ETV plus adefovir (ADV) as rescue therapy for HBV rtA181V/T single mutation. PATIENTS AND METHODS: A total of 30 patients who received ETV alone (1.0 mg/day, n = 16) or ETV plus ADV (10.0 mg/day, n = 14) over 48 weeks between April 2008 and October 2011 were enrolled. Virological, biochemical, and serological response at 48 weeks of rescue therapy were investigated retrospectively. RESULTS: No significant difference in baseline characteristics was observed between the ETV group and the ETV plus ADV group. Virological response showed complete response (62.5 vs. 42.9%), partial response (6.3 vs. 28.6%), non-response (25.0 vs. 28.6%), and virological breakthrough (6.3 vs. 0%) in the two groups, respectively. Virological response did not statistically differ between both groups (P = 0.278). No significant difference in the mean reduction of serum HBV DNA and biochemical response was observed between both groups (4.3 +/- 2.9 vs. 4.1 +/- 1.8 log 10 IU/ml; P = 0.294 and 88.9 vs. 100%; P = 1.000, respectively). In addition, no significant difference in HBeAg loss or seroconversion was observed between the two groups (26.7 vs. 28.6%; P = 1.000). CONCLUSIONS: ETV monotherapy and ETV plus ADV therapy were clinically effective and comparable as rescue therapy for HBV rtA181V/T mutants alone. PMID- 26831606 TI - Predictors of incomplete optical colonoscopy using computed tomographic colonography. AB - BACKGROUND/AIMS: Optical colonoscopy (OC) is the primary modality for investigation of colonic pathology. Although there is data on demographic factors for incomplete OC, paucity of data exists for anatomic variables that are associated with an incomplete OC. These anatomic variables can be visualized using computed tomographic colonography (CTC). We aim to retrospectively identify variables associated with incomplete OC using CTC and develop a scoring method to predict the outcome of OC. PATIENTS AND METHODS: In this case-control study, 70 cases ( with incomplete OC) and 70 controls (with complete OC) were identified. CTC images of cases and controls were independently reviewed by a single CTC radiologist. Demographic and anatomical parameters were recorded. Data was examined using descriptive linear statistics and multivariate logistic regression model. RESULTS: On analysis, female gender (80% vs 58.6% P = 0.007), prior abdominal/pelvic surgeries (51.4% vs 14.3% P < 0.001), colonic length (187.6 +/- 30.0 cm vs 163.8 +/- 27.2 cm P < 0.001), and number of flexures (11.4 +/- 3.1 vs 8.4 +/- 2.9 P < 0.001) increased the risk for incomplete OC. No significant association was observed for increasing age (P = 0.881) and history of severe diverticulosis (P = 0.867) with incomplete OC. A scoring system to predict the outcome of OC is proposed based on CTC findings. CONCLUSION: Female gender, prior surgery, and increasing colonic length and tortuosity were associated with incomplete OC, whereas increasing age and history of severe diverticulosis were not. These factors may be used in the future to predict those patients who are at risk of incomplete OC. PMID- 26831607 TI - Healing acceleration of acetic acid-induced colitis by marigold (Calendula officinalis) in male rats. AB - BACKGROUND/AIM: Ulcerative colitis (UC) is a type of chronic inflammatory bowel disease with unknown etiology. Several therapeutic strategies such as consumption of medicinal plants have been used for its treatment. The aim of this study was to evaluate healing effects of Calendula officinalis hydroalcoholic extract in experimentally induced UC in rat. MATERIALS AND METHODS: Ninety-six rats, weighing 200 +/- 20 g, were randomly divided into eight equal groups. UC induced by 3% acetic acid and oral doses of C. officinalis extract, 1500 and 3000 mg/kg, and enema (gel 10% and 20%) were given. Two groups as positive controls were given asacol (enema) and oral mesalamine. Negative control groups were given normal saline and base gel. On days 3 and 7, intestinal histopathology and weight changes, plus oxidative stress indices including malondialdehyde (MDA) level and myeloperoxidase (MPO) activity were assayed. RESULTS: A significant increase in the body weight of rats was seen in the group given C. officinalis extract 3000 mg/kg orally, oral mesalamine, and 20% intracolonic gel form of marigold extract compared with negative control and base gel groups during the experimental period. Acute inflammation and granular atrophy after UC induction were resolved completely completely by both 20% intracolonic gel and 3000 mg/kg orally. An increase in MPO activity and a decrease in MDA level in response to oral and intracolonic gel form of C. officinalis were observed 3 and and 7 days after treatment (P < 0.05). CONCLUSION: Our results indicate that oral and enema forms of hydroalcoholic extract of C. officinalis can be offered as are potential therapeutic agents for UC induced in rats. PMID- 26831608 TI - Noninvasive fibrosis marker can predict recurrence of hepatocellular carcinoma after radiofrequency ablation. AB - BACKGROUND/AIMS: Tumor recurrence after curative therapy is common for patients with hepatocellular carcinoma (HCC). As fibrosis and chronic inflammation contribute to the progression of HCC, we aimed to identify the predictive value of inflammatory and fibrosis markers for HCC recurrence after curative therapy using radiofrequency ablation (RFA). MATERIALS AND METHODS: We retrospectively reviewed the records of patients with HCC treated with RFA between October 2005 and September 2013. The median duration of follow-up was 40 months (4-95 months). Inflammatory and fibrosis markers and demographic and clinical data were analyzed by Cox proportional hazards model using univariate and multivariate analyses and longitudinal analysis. RESULTS: A total of 98 patients were included for analysis. There were 54 cases of HCC recurrence (55.1%). The aspartate aminotransferase-to-platelet ratio index (APRI; 2.3 +/- 1.8 vs. 1.3 +/- 1.4, P = 0.018) was significantly higher in the recurrence group than in the recurrence free group. In multivariate analysis, APRI (hazard ratio, 2.64; confidence interval, 1.488-4.714; P = 0.001) was an independent risk factor for tumor recurrence. In particular, patients with APRI >1.38 showed a higher recurrence rate than patients with APRI <= 1.38 (P < 0.001). Longitudinal analysis showed persistently higher APRI values when assessed 12 months after RFA in patients who developed recurrence during follow-up than those who remained recurrence-free. CONCLUSIONS: These findings show that a high APRI value is associated with HCC recurrence after RFA. Therefore, APRI could play an important role in predicting HCC recurrence after RFA. PMID- 26831609 TI - Factors influencing challenging colonoscopies during anesthesiologist-assisted deep sedation. AB - BACKGROUND/AIM: Increased demand for colon cancer screening procedures can significantly impact on routine colonoscopy management at dedicated facilities, prompting a review of the factors that can negatively affect workflow. Although potential adverse effects and impact on costs of deep sedation have been documented elsewhere, this study focuses on variables that can influence performance of colonoscopy in deep sedation and interfere with normal procedure scheduling in settings where the presence of an anesthesiologist is mandatory. PATIENTS AND METHODS: We performed a cross-sectional study of the activities of a colonoscopy screening unit, applying Bayesian Network (BN) analysis, designed to assess interdependencies among variables that can affect a process in complex, multidimensional systems. The study was performed at a teaching hospital where endoscopists and anesthesiologists of varying work experience operate on a rota basis. During a six-month period, we analyzed 1485 consecutive colonoscopies performed under deep propofol sedation, administered by an anesthesiologist via hand-controlled syringe. The BN was constructed with the variables: Gender, age, ASA status, bowel preparation, baseline blood pressure, endoscopist's experience, anesthesiologist's experience, presence of polypectomy, and the target node, "challenging procedure." This previously undefined category refers to any events disrupting the scheduled rota. RESULT AND CONCLUSION: Two distinct networks were identified. One deals mainly with relationships among the variables, patients' demographic and clinical characteristics (procedures with polypectomy, ASA and baseline blood pressure). The other explains relationships among the variables, "challenging procedure," bowel preparation, and endoscopist's experience. The factors associated with the anesthesiologist's activity do not influence challenging colonoscopies. PMID- 26831611 TI - A prospective trial in Saudi Arabia comparing the 14-day standard triple therapy with the 10-day sequential therapy for treatment of Helicobacter pylori infection: A further confirmation of "Geographic Weight". PMID- 26831610 TI - Effect of telmisartan on histological activity and fibrosis of non-alcoholic steatohepatitis: A 1-year randomized control trial. AB - BACKGROUND/AIM: Telmisartan can attenuate two hit pathogenesis of non-alcoholic steatohepatitis (NASH). This study aimed to observe the effect of Telmisartan on non-alcoholic fatty liver disease (NAFLD) activity score (NAS) and fibrosis score in NASH patients. PATIENTS AND METHODS: A total of 50 NASH patients were randomized; 35 of group 1 were treated with Telmisartan 40/80 mg once daily with life style modification (TL) and 15 of group 2 underwent only life style modification (L) for 1 year. At the end, 20 of TL group and 10 of L group were analyzed. Those who showed NAS improvement >= 2 or NAS improvement >= 1 with fibrosis improvement >= 1 were considered as responders. RESULTS: Baseline alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin resistance index, components of metabolic syndrome, age, and sex were similar in both groups. At the end of study, NAS improvement in TL and L groups was 2.15 +/- 1.66 and 1.10 +/- 0.57 (P = 0.017) and fibrosis improvement was 0.65 +/- 0.93 and -0.30 +/- 0.48 (P = 0.001), respectively. NAS improved by >= 2 in 13 (65%) and 2 (20%) patients and fibrosis score improved by >= 1 in 8 (40%) patients and none of the patients in TL group and L group, respectively. Telmisartan and life style modification could improve steatosis, ballooning, lobular inflammation, and fibrosis. Life style modification could improve ballooning only, but fibrosis deteriorated. TL group showed improvement in NAS and fibrosis score [P value: 0.035; odds ratio (OR) =92.07, confidence interval (CI) =1.39-6106] to the level of response by regression analysis. Weight reduction and improvement of metabolic syndrome did not influence the response. There were similar minor adverse events in both groups. CONCLUSION: Telmisartan improved NAS and fibrosis score in NASH with insignificant adverse events. PMID- 26831612 TI - Response to: Treatment prolongation or quadruple therapy:- Individualization by geographical region. PMID- 26831613 TI - Updated Helicobacter pylori management in 2015. PMID- 26831614 TI - Response to: Reply on "Renewed Helicobacter pylori management and therapy in 2015". PMID- 26831615 TI - Celiac disease among symptom-free children-more than what is expected. PMID- 26831616 TI - Prevalence of celiac disease in Saudi children: Is it underestimated? PMID- 26831617 TI - Response to: Serum paraoxonase and malondialdehyde levels in asymptomatic cholelithiasis. PMID- 26831619 TI - Application of GIS technology in public health: successes and challenges. AB - The uptake and acceptance of Geographic Information Systems (GIS) technology has increased since the early 1990s and public health applications are rapidly expanding. In this paper, we summarize the common uses of GIS technology in the public health sector, emphasizing applications related to mapping and understanding of parasitic diseases. We also present some of the success stories, and discuss the challenges that still prevent a full scope application of GIS technology in the public health context. Geographical analysis has allowed researchers to interlink health, population and environmental data, thus enabling them to evaluate and quantify relationships between health-related variables and environmental risk factors at different geographical scales. The ability to access, share and utilize satellite and remote-sensing data has made possible even wider understanding of disease processes and of their links to the environment, an important consideration in the study of parasitic diseases. For example, disease prevention and control strategies resulting from investigations conducted in a GIS environment have been applied in many areas, particularly in Africa. However, there remain several challenges to a more widespread use of GIS technology, such as: limited access to GIS infrastructure, inadequate technical and analytical skills, and uneven data availability. Opportunities exist for international collaboration to address these limitations through knowledge sharing and governance. PMID- 26831620 TI - First Evidence of DAAM1 Localization During the Post-Natal Development of Rat Testis and in Mammalian Sperm. AB - Dishevelled-associated activator of morphogenesis 1 (DAAM1) is a formin-family protein involved in nucleation of unbranched actin filaments and in cytoskeletal organization through Wnt-Dishevelled PCP pathway, which participates in essential biological processes, such as cell polarity, movement, and adhesion during morphogenesis and organogenesis. While its role has been investigated during development and in somatic cells, its potential association with the germinal compartment and reproduction is still unexplored. In this work, we assessed the possible association of DAAM1 with the morphogenesis of rat testis. We studied its expression and profiled its localization versus actin and tubulin, during the first wave of spermatogenesis and in the adult gonad (from 7 to 60 dpp). We show that, in mitotic phases, DAAM1 shares its localization with actin in Sertoli cells, gonocytes, and spermatogonia. Later, during meiosis, both proteins are found in spermatocytes, while only actin is detectable at the forming blood testis barrier. DAAM1, then, follows the development of the acrosome system throughout spermiogenesis, and it is finally retained inside the cytoplasmic droplet in mature gametes, as corroborated by additional immunolocalization data on both rat and human sperm. Unlike the DAAM1, actin keeps its localization in Sertoli cells, and tubulin is associated with their protruding cytoplasm during the process. Our data support, for the first time, the hypothesis of a role for DAAM1 in cytoskeletal organization during Mammalian testis morphogenesis and gamete progression, while also hinting at its possible investigation as a morphological marker of germ cell and sperm physiology. J. Cell. Physiol. 231: 2172-2184, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26831621 TI - Disassembly of micelles to impart donor and acceptor gradation to enhance organic solar cell efficiency. AB - A transparent, conducting and low surface energy surface was prepared by disassembly of anionic micelles, which altered the orientation of the donor polymer and imparted gradation between the donor and acceptor. This configuration increased the solar cell device efficiency. PMID- 26831618 TI - Reversible interconversion and maintenance of mammary epithelial cell characteristics by the ligand-regulated EGFR system. AB - Epithelial cell plasticity is controlled by extracellular cues, but the underlying mechanisms remain to be fully understood. Epidermal growth factor (EGF) and amphiregulin (AREG) are high- and low-affinity ligands for EGF receptor (EGFR), respectively. EGFR signaling is known to promote epithelial-mesenchymal transition (EMT) by the activation of ERK and the induction of an EMT transcription factor, ZEB1. Here, we demonstrate that ligand-switching between EGF and AREG at equivalent molarity reversibly interconverts epithelial and mesenchymal-like states of EGFR signal-dependent mammary epithelial cells. The EGF- and AREG-cultured cells also differ in their epithelial characteristics, including the expression of cell surface markers, the mode of migration and the ability for acinus-formation. The ligand-switching between EGF and AREG temporally alters strength of the shared EGFR-ERK signaling. This alteration inverts relative expression levels of ZEB1 and its antagonizing microRNAs, miR 205 and miR-200c, those are critical determinants of the epithelial phenotype. Further, AREG-induced EGFR accumulation on the plasma membrane compensates for the weak association between AREG and EGFR. The EGFR dynamics enables AREG to support proliferation as efficiently as EGF at equivalent molarity and to maintain epithelial characteristics. Our findings reveal a role of EGFR ligands generated signal strength in the regulation of mammary epithelial cell plasticity. PMID- 26831622 TI - Characterization of IRE1 ribonuclease-mediated mRNA decay in plants using transient expression analyses in rice protoplasts. AB - In some eukaryotes, endoplasmic reticulum (ER) stress induces regulated inositol requiring enzyme 1 (IRE1)-dependent decay (RIDD) of mRNAs. Recently, the expression levels of the mRNAs encoding some secretory proteins were reported to be downregulated by RIDD in the vegetative tissues of plants. However, the characteristics of plant RIDD have been insufficiently investigated due to difficulty of in planta analyses. Here, the RIDD susceptibilities of various mRNAs that are difficult to analyze in planta were examined using transient expression analyses of rice protoplasts. In this system, the mRNAs encoding three rice seed storage proteins (SSPs) - namely alpha-globulin, 16-kDa prolamin and 10 kDa prolamin - were downregulated in response to ER stress. The rapid ER stress induced degradation of these mRNAs was repressed in cells in which the ribonuclease activity of IRE1 was specifically abolished by genome editing, suggesting that the mRNAs encoding certain SSPs are strong targets of RIDD. Furthermore, we investigated whether these RIDD targets are substrates of the IRE1 ribonuclease using a recombinant IRE1 protein, and identified candidate IRE1 mediated cleavage sites. Overall, the results demonstrate the existence of a post transcriptional mechanism of regulation of SSPs, and illustrate the basic and multifaceted characteristics of RIDD in higher plants. PMID- 26831623 TI - Salvage Radiotherapy for Postoperative Biochemical Failure of Prostate Cancer: The Path Toward Personalized Medicine. PMID- 26831624 TI - Why Is Bigger Not Always Better in Primary Health Care Practices? The Role of Mediating Organizational Factors. AB - Size of primary health care (PHC) practices is often used as a proxy for various organizational characteristics related to provision of care. The objective of this article is to identify some of these organizational characteristics and to determine the extent to which they mediate the relationship between size of PHC practice and patients' experience of care, preventive services, and unmet needs. In 2010, we conducted population and organization surveys in 2 regions of the province of Quebec. We carried out multilevel linear and logistic regression analyses, adjusting for respondents' individual characteristics. Size of PHC practice was associated with organizational characteristics and resources, patients' experience of care, unmet needs, and preventive services. Overall, the larger the size of a practice, the higher the accessibility, but the lower the continuity. However, these associations faded away when organizational variables were introduced in the analysis model. This result supports the hypothesized mediating effect of organizational characteristics on relationships between practice size and patients' experience of care, preventive services, and unmet needs. Our results indicate that size does not add much information to organizational characteristics. Using size as a proxy for organizational characteristics can even be misleading because its relationships with different outcomes are highly variable. PMID- 26831625 TI - Organization and Finance of China's Health Sector: Historical Antecedents for Macroeconomic Structural Adjustment. AB - China has exploded onto the world economy over the past few decades and is undergoing rapid transformation toward relatively more services. The health sector is an important part of this transition. This article provides a historical account of the development of health care in China since 1949. It also focuses on health insurance and macroeconomic structural adjustment to less saving and more consumption. In particular, the question of how health insurance impacts precautionary savings is considered. Multivariate analysis using data from 1990 to 2012 is employed. The household savings rate is the dependent variable in 3 models segmented for rural and urban populations. Independent variables include out-of-pocket health expenditures, health insurance payouts, housing expenditure, education expenditure, and consumption as a share of gross domestic product (GDP). Out-of-pocket health expenditures were positively correlated with household savings rates. But health insurance remains weak, and increased payouts by health insurers have not been associated with lower levels of household savings so far. Housing was positively correlated, whereas education had a negative association with savings rates. This latter finding was unexpected. Perhaps education is perceived as investment and a substitute for savings. China's shift toward a more service-oriented economy includes growing dependence on the health sector. Better health insurance is an important part of this evolution. The organization and finance of health care is integrally linked with macroeconomic policy in an environment constrained by prevailing institutional convention. Problems of agency relationships, professional hegemony, and special interest politics feature prominently, as they do elsewhere. China also has a dual approach to medicine relying heavily on providers of traditional Chinese medicine. Both of these segments will take part in China's evolution, adding another layer of complexity to policy. PMID- 26831626 TI - Magnetic Resonance Imaging in Diagnosis and Monitoring of Hepatocellular Carcinoma in Liver Transplantation: A Comprehensive Review. AB - Hepatocellular carcinoma (HCC) is the most common primary liver cancer. One of the most important risk factors of HCC is cirrhosis. The optimal treatment of HCC is liver transplantation, since it treats both the underlying cirrhosis and the cancer. Patients that have risk factors should be included in surveillance programs since HCC can be cured only during the early stages. Surveillance can be performed by ultrasonography (US), which is an inexpensive, non-invasive, and widely available technique, but it is considered to have a low sensitivity. If a suspicious lesion is detected on US exam, computerized tomography (CT) or magnetic resonance imaging (MRI) can be used to further evaluate this lesion. MRI is considered to be superior to CT because it has greater contrast resolution and tissue characterization. In this article, we present a review of MRI for HCC in liver transplantation (LT) with a focus on characteristic MR features of this tumor and current guidelines. PMID- 26831627 TI - Narrow distribution of cyanophage psbA genes observed in two paddy waters of Northeast China by an incubation experiment. PMID- 26831628 TI - The Ability of Men's Lacrosse Helmets to Reduce the Dynamic Impact Response for Different Striking Techniques in Women's Field Lacrosse. AB - BACKGROUND: Women's field lacrosse is described as a noncontact game relying primarily on rules to decrease the risk of head injuries. Despite not allowing head contact, however, concussions continue to be reported in women's field lacrosse. PURPOSE: To assess the ability of men's lacrosse helmets to decrease linear and angular acceleration for different striking techniques in women's field lacrosse. STUDY DESIGN: Controlled laboratory study. METHODS: A helmeted and unhelmeted Hybrid III 50th Percentile headform was attached to a Hybrid III neckform and were subjected to impacts by 8 striking techniques. Eleven athletic females completed 5 slashing techniques, while physical reconstruction equipment was used to simulate falls and shoulder and ball impacts to the head. Three trials were conducted for each condition, and peak resultant linear and angular accelerations of the headform were measured. RESULTS: Falls produced the highest linear and angular acceleration, followed by ball and high-velocity stick impacts. Low-velocity stick impacts were found to produce the lowest linear and angular accelerations. Men's lacrosse helmets significantly decreased linear and angular accelerations in all conditions, while unhelmeted impacts were associated with high accelerations. CONCLUSION: If women's field lacrosse is played within the rules, only falls were found to produce high linear and angular acceleration. However, ball and high-velocity stick impacts were found to produce high linear and angular accelerations. These linear and angular accelerations were found to be within the ranges reported for concussion. When the game is not played within the rules, men's lacrosse helmets provide an effective method of reducing linear and angular accelerations. Thus, women's field lacrosse may be able to reduce the occurrence of high linear and angular acceleration impacts by having governing bodies improving rules, implementing the use of helmets, or both. CLINICAL RELEVANCE: Identifying striking techniques that produce high linear and angular acceleration specific to women's lacrosse and measuring the capacity of a men's lacrosse helmet to reduce linear and angular acceleration. PMID- 26831629 TI - Intra-articular Autologous Conditioned Plasma Injections Provide Safe and Efficacious Treatment for Knee Osteoarthritis: An FDA-Sanctioned, Randomized, Double-blind, Placebo-controlled Clinical Trial. AB - BACKGROUND: Platelet-rich plasma (PRP) injections have become an intriguing treatment option for osteoarthritis (OA), particularly OA of the knee. Despite the plethora of PRP-related citations, there is a paucity of high-level evidence that is comparable, cohort specific, dose controlled, injection protocol controlled, and double-blinded. PURPOSE: To determine the safety and efficacy of leukocyte-poor PRP autologous conditioned plasma (ACP) for knee OA treatment through a feasibility trial regulated by the US Food and Drug Administration (FDA). STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: In accordance with FDA protocol, patient selection was based on strict inclusion/exclusion criteria; 114 patients were screened, and 30 were ultimately included in the study. These patients were randomized to receive either ACP (n = 15) or saline placebo (n = 15) for a series of 3 weekly injections. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores served as the primary efficacy outcome measure. Patients were followed for 1 year. RESULTS: No adverse events were reported for ACP administration. Furthermore, the results demonstrated no statistically significant difference in baseline WOMAC scores between the 2 groups. However, in the ACP group, WOMAC scores at 1 week were significantly decreased compared with baseline scores, and the scores for this group remained significantly lower throughout the study duration. At the study conclusion (12 months), subjects in the ACP group had improved their overall WOMAC scores by 78% from their baseline score, compared with 7% for the placebo group. CONCLUSION: ACP is safe and provides quantifiable benefits for pain relief and functional improvement with regard to knee OA. No adverse events were reported for ACP administration. After 1 year, WOMAC scores for the ACP subjects had improved by 78% from their baseline score, whereas scores for the placebo control group had improved by only 7%. Other joints affected with OA may also benefit from this treatment. PMID- 26831630 TI - Outcomes After Arthroscopic Treatment of Femoroacetabular Impingement for Patients With Borderline Hip Dysplasia. AB - BACKGROUND: The outcomes of hip arthroscopy in the treatment of dysplasia are variable. Historically, arthroscopic treatment of severe dysplasia (lateral center-edge angle [LCEA] <18 degrees ) resulted in poor outcomes and iatrogenic instability. However, in milder forms of dysplasia, favorable outcomes have been reported. PURPOSE: To compare outcomes after hip arthroscopy for femoroacetabular impingement (FAI) in borderline dysplastic (BD) patients compared with a control group of nondysplastic patients. STUDY DESIGN: Cohort study; Level of evidence, 3 METHODS: Between March 2009 and July 2012, a BD group (LCEA, 18 degrees -25 degrees ) of 46 patients (55 hips) was identified. An age- and sex-matched control group of 131 patients (152 hips) was also identified (LCEA, 25 degrees 40 degrees ). Patient-reported outcome scores, including the modified Harris Hip Score (mHHS), the Hip Outcome Score-Activities of Daily Living (HOS-ADL) and Sport-Specific Subscale (HOS-SSS), and the International Hip Outcome Tool (iHOT 33), were collected preoperatively and at 1 and 2 years postoperatively. RESULTS: The mean LCEA was 22.4 degrees +/- 2.0 degrees (range, 18.4 degrees -24.9 degrees ) in the BD group and 31.0 degrees +/- 3.1 degrees (range, 25.4 degrees -38.7 degrees ) in the control group (P < .001). The mean preoperative alpha angle was 66.3 degrees +/- 9.9 degrees in the BD group and 61.7 degrees +/- 13.0 degrees in the control group (P = .151). Cam decompression was performed in 98.2% and 99.3% of cases in the BD and control groups, respectively; labral repair was performed in 69.1% and 75.3% of the BD and control groups, respectively, with 100% of patients having a complete capsular closure performed in both groups. At a mean follow-up of 31.3 +/- 7.6 months (range, 23.1-67.3 months) in unrevised patients and 21.6 +/- 13.3 months (range, 4.7-40.6 months) in revised patients, there was significant improvement (P < .001) in all patient reported outcome scores in both groups. Multiple regression analysis did not identify any significant differences between groups. Importantly, female sex did not appear to be a predictor for inferior outcomes. Two patients (4.3%) in the BD group and 6 patients (4.6%) in the control group required revision arthroscopy during the study period. CONCLUSION: Favorable outcomes can be expected after the treatment of impingement in patients with borderline dysplasia when labral refixation and capsular closure are performed, with comparable outcomes to nondysplastic patients. Further follow-up in larger cohorts is necessary to prove the durability and safety of hip arthroscopy in this challenging group and to further explore potential sex-related differences in outcome. PMID- 26831631 TI - Alteration of Stress Distribution Patterns in Symptomatic Valgus Instability of the Elbow in Baseball Players: A Computed Tomography Osteoabsorptiometry Study. AB - BACKGROUND: Repetitive valgus stress applied during a throwing motion can lead to various elbow disturbances, including ulnar collateral ligament (UCL) injury. Subchondral bone density reportedly reflects the cumulative force on a joint surface under actual loading conditions. PURPOSE: (1) To evaluate the distribution of subchondral bone density across the elbow joint in asymptomatic baseball pitchers and symptomatic valgus instability pitchers and (2) to clarify the alterations in stress distribution pattern associated with symptomatic UCL insufficiency pitching activities. STUDY DESIGN: Controlled laboratory study. METHODS: Computed tomography (CT) imaging data were collected from the dominant side elbow of 7 nonathletic volunteers (controls), 12 asymptomatic pitchers (asymptomatic group), and 12 symptomatic valgus instability pitchers with UCL insufficiency (symptomatic group). Bone mineral density across the elbow joint was measured with CT osteoabsorptiometry. A 2-dimensional mapping model was divided into 4 areas of the distal end of the humerus and 5 areas of the ulna with the radial head. The locations and percentages of high-density areas on the articular surface were quantitatively analyzed. RESULTS: High-density areas in the asymptomatic and symptomatic groups were found in the anterolateral and posteromedial parts of the humerus and in the radial head, posteromedial to the ulna. The high-density areas in the anterior and posteromedial of the humerus, the radial head, and the posteromedial part of the ulna in the controls were smaller than those in the baseball group. In the symptomatic group, the percentages of high-density areas in the anterolateral part of the humerus (mean, 36.3%; 95% CI, 31.9%-40.7%) and the anterolateral part of the ulna (mean, 31.7%; 95% CI, 24.3%-39.1) were significantly greater than those in the asymptomatic group (P = .047 and P < .0001, respectively). CONCLUSION: Symptomatic UCL insufficiency was associated with characteristic high-stress distribution patterns on the anterolateral part of the capitellum and the anterolateral part of the ulna. The current results indicate that symptomatic UCL insufficiency produces excessive and cumulative stress in the elbow joint. CLINICAL RELEVANCE: The information obtained from the CT images can useful for early detection of overstress conditions of the elbow joint. PMID- 26831632 TI - An In Vitro Robotic Assessment of the Anterolateral Ligament, Part 2: Anterolateral Ligament Reconstruction Combined With Anterior Cruciate Ligament Reconstruction. AB - BACKGROUND: Recent biomechanical studies have demonstrated that an extra articular lateral knee structure, most recently referred to as the anterolateral ligament (ALL), contributes to overall rotational stability of the knee. However, the effect of anatomic ALL reconstruction (ALLR) in the setting of anterior cruciate ligament (ACL) reconstruction (ACLR) has not been biomechanically investigated or validated. PURPOSE/HYPOTHESIS: The purpose of this study was to investigate the biomechanical function of anatomic ALLR in the setting of a combined ACL and ALL injury. More specifically, this investigation focused on the effect of ALLR on resultant rotatory stability when performed in combination with concomitant ACLR. It was hypothesized that ALLR would significantly reduce internal rotation and axial plane translation laxity during a simulated pivot shift test compared with isolated ACLR. STUDY DESIGN: Controlled laboratory study. METHODS: Ten fresh-frozen cadaveric knees were evaluated with a 6 degrees of freedom robotic system. Knee kinematics were evaluated with simulated clinical examinations including a simulated pivot-shift test consisting of coupled 10-N.m valgus and 5-N.m internal rotation torques, a 5-N.m internal rotation torque, and an 88-N anterior tibial load. Kinematic differences between ACLR with an intact ALL, ACLR with ALLR, and ACLR with a deficient ALL were compared with the intact state. Single-bundle ACLR tunnels and ALLR tunnels were placed anatomically according to previous quantitative anatomic attachment descriptions. RESULTS: Combined anatomic ALLR and ACLR significantly improved the rotatory stability of the knee compared with isolated ACLR in the face of a concurrent ALL deficiency. During a simulated pivot-shift test, ALLR significantly reduced internal rotation and axial plane tibial translation when compared with ACLR with an ALL deficiency. Isolated ACLR for the treatment of a combined ACL and ALL injury was not able to restore stability of the knee, resulting in a significant increase in residual internal rotation laxity. ALLR did not affect anterior tibial translation; no significant differences were observed between the varying ALL conditions with ACLR except between ACLR with an intact ALL and ACLR with a deficient ALL at 0 degrees of flexion. CONCLUSION: In the face of a combined ACL and ALL deficiency, concurrent ACLR and ALLR significantly improved the rotatory stability of the knee compared with solely reconstructing the ACL. CLINICAL RELEVANCE: Significant increases in residual internal rotation and laxity during the pivot-shift test may exist in both acute and chronic settings of an ACL deficiency and in patients treated with isolated ACLR for a combined ACL and ALL deficiency. For this subset of patients, surgical treatment of the ALL, in addition to ACLR, should be considered to restore knee stability. PMID- 26831633 TI - Recurrent Anterior Shoulder Instability With Combined Bone Loss: Treatment and Results With the Modified Latarjet Procedure. AB - BACKGROUND: Recurrent anterior glenohumeral dislocation in the setting of an engaging Hill-Sachs lesion is high. The Latarjet procedure has been well described for restoring glenohumeral stability in patients with >25% glenoid bone loss. However, the treatment for patients with combined humeral head and mild (<25%) glenoid bone loss remains unclear. PURPOSE/HYPOTHESIS: This study reports on the outcomes of the modified Latarjet for patients with combined humeral and glenoid defects and compares the results for patients with <=25% glenoid bone loss versus patients with >25% glenoid bone loss. The hypothesis was that the 2 groups would have equivalent subjective outcomes and recurrence rates. STUDY DESIGN: Cohort Study; Level of evidence, 3. METHODS: Modified Latarjet was performed in 40 patients with recurrent anterior shoulder instability, engaging Hill-Sachs by examination confirmed with arthroscopy, and <=25% anterior glenoid bone loss (group A). A second group of 12 patients were identified to have >25% glenoid bone loss with an engaging Hill-Sachs lesion (group B). The mean follow up time was 3.5 years. All patients were assessed for their risk of recurrence using the Instability Severity Index score and Beighton score and had preoperative 3-dimensional imaging to assess humeral and glenoid bone loss. Single Assessment Numeric Evaluation (SANE), Western Ontario Shoulder Instability Index (WOSI), recurrence rate, radiographs, range of motion, and dynamometer strength were used to assess outcomes. A multivariate analysis was performed. RESULTS: Glenoid bone loss averaged 15% in group A compared with 34% in group B. Both groups had comparable WOSI scores (356 vs 475; P = .311). In multivariate analysis, the number of previous surgeries and Beighton score were directly correlated with WOSI score in Latarjet patients. The SANE score was better in group A (86 vs 77; P = .02). Group B experienced more loss of external rotation (9.2 degrees vs 15.8 degrees ; P = .0001) and weaker thumbs-down abduction and external rotation strength (P < .032). Subscapularis, abduction, and external rotation strength averaged at least 75% of the contralateral shoulder in both groups. Graft resorption was similar in both groups (32% vs 33%; P < .999). The overall recurrent instability rate for the study, defined as any subsequent subluxations or dislocation, was 15%; recurrent instability rates (15% vs 17%; P > .999) were similar for both groups. The complication rate was 25% for both groups. CONCLUSION: The modified Latarjet procedure provides satisfactory outcomes for patients with combined bone loss, which is known to have high recurrence rates with traditional arthroscopic stabilization. Previous surgical stabilization procedures and the Beighton score adversely affect outcome after modified Latarjet. Furthermore, the number of previous surgeries and Beighton score can be used to predict WOSI score in Latarjet patients. Further study is needed to determine if these results hold true in the long term. PMID- 26831634 TI - Causality and the Levels of Selection. AB - When is it sensible to say that group selection has shaped organismal design? This question has prompted many replies but few credible solutions. New work that exposes the causal relationships between phenotypes and fitness may finally settle the matter - and a few other things besides. PMID- 26831635 TI - Recombination Rate Evolution and the Origin of Species. AB - A recipe for dissolving incipient species into a continuum of phenotypes is to recombine their genetic material. Therefore, students of speciation have become increasingly interested in the mechanisms by which recombination between locally adapted lineages is reduced. Evidence abounds that chromosomal rearrangements, via their suppression of recombination during meiosis in hybrids, play a major role in adaptation and speciation. By contrast, genic modifiers of recombination rates have been largely ignored in studies of speciation. We show how both types of reduction in recombination rates facilitate divergence in the face of gene flow, including the early stages of adaptive divergence, the persistence of species after secondary contact, and reinforcement. PMID- 26831636 TI - Noise level in intensive care units of a public university hospital in Santa Marta (Colombia). AB - OBJECTIVE: To evaluate the noise level in adult, pediatric and neonatal intensive care units of a university hospital in the city of Santa Marta (Colombia). DESIGN: A descriptive, observational, non-interventional study with follow-up over time was carried out. MATERIALS AND METHODS: Continuous sampling was conducted for 20 days for each unit using a type i sound level meter, filter frequency in A weighting and Fast mode. We recorded the maximum values, the 90th percentile as background noise, and the continuous noise level. RESULTS: The mean hourly levels in the adult unit varied between 57.40+/-1.14-63.47+/-2.13dBA, with a maximum between 71.55+/-2.32-77.22+/-1.94dBA, and a background noise between 53.51+/-1.16-60.26+/-2.10dBA; in the pediatric unit the mean hourly levels varied between 57.07+/-3.07-65.72+/-2.46dBA, with a maximum of 68.69+/-3.57-79.06+/ 2.34dBA, and a background noise between 53.33+/-3.54-61.96+/-2.85dBA; the neonatal unit in turn presented mean hourly values between 59.54+/-2.41-65.33+/ 1.77dBA, with a maximum value between 67.20+/-2.13-77.65+/-3.74dBA, and a background noise between 55.02+/-2.03-58.70+/-1.95dBA. Analysis of variance revealed a significant difference between the hourly values and between the different units, with the time of day exhibiting a greater influence. CONCLUSIONS: The type of unit affects the noise levels in intensive care units, the pediatric unit showing the highest values and the adult unit the lowest values. However, the parameter exerting the greatest influence upon noise level is the time of day, with higher levels in the morning and evening, and lower levels at night and in the early morning. PMID- 26831637 TI - Photolytic degradation of tris-(2,3-dibromopropyl) isocyanurate (TBC) in aqueous systems. AB - Tris-(2,3-dibromopropyl) isocyanurate (TBC) is a brominated flame retardant, which has been found in several environmental and biological matrices in recent years. TBC has aroused high environmental concerns because of its bioaccumulation and biological toxicity. This work studied photodegradation of TBC for the first time. The optimal degradation conditions have been found that 95% of 10 MUmol/LTBC was effectively decomposed after 120 min of UV radiation. UV lamp was found to be more effective than Xe lamp on the photodegradation. The degradation rate of TBC increased with increasing light intensity. Under UV illumination, the effect of pH on the photodegradation of TBC could be ignored and degradation reactions followed the pseudo-first-order kinetics. The addition of [Formula: see text] could not accelerate the degradation of TBC. The quenching experiments showed that TBC was directly photodegraded by UV illumination. These findings suggest that UV photodegradation is a potential method for the removal of TBC in aqueous solutions. PMID- 26831638 TI - Decreased Fronto-Limbic Activation and Disrupted Semantic-Cued List Learning in Major Depressive Disorder. AB - OBJECTIVES: Individuals with major depressive disorder (MDD) demonstrate poorer learning and memory skills relative to never-depressed comparisons (NDC). Previous studies report decreased volume and disrupted function of frontal lobes and hippocampi in MDD during memory challenge. However, it has been difficult to dissociate contributions of short-term memory and executive functioning to memory difficulties from those that might be attributable to long-term memory deficits. METHODS: Adult males (MDD, n=19; NDC, n=22) and females (MDD, n=23; NDC, n=19) performed the Semantic List Learning Task (SLLT) during functional magnetic resonance imaging. The SLLT Encoding condition consists of 15 lists, each containing 14 words. After each list, a Distractor condition occurs, followed by cued Silent Rehearsal instructions. Post-scan recall and recognition were collected. Groups were compared using block (Encoding-Silent Rehearsal) and event related (Words Recalled) models. RESULTS: MDD displayed lower recall relative to NDC. NDC displayed greater activation in several temporal, frontal, and parietal regions, for both Encoding-Silent Rehearsal and the Words Recalled analyses. Groups also differed in activation patterns in regions of the Papez circuit in planned analyses. The majority of activation differences were not related to performance, presence of medications, presence of comorbid anxiety disorder, or decreased gray matter volume in MDD. CONCLUSIONS: Adults with MDD exhibit memory difficulties during a task designed to reduce the contribution of individual variability from short-term memory and executive functioning processes, parallel with decreased activation in memory and executive functioning circuits. Ecologically valid long-term memory tasks are imperative for uncovering neural correlates of memory performance deficits in adults with MDD. PMID- 26831639 TI - The limitations of 'Black MSM' as a category: Why gender, sexuality, and desire still matter for social and biomedical HIV prevention methods. AB - The USA faces disproportionate and increasing HIV incidence rates among Black men who have sex with men (BMSM). New biomedical technologies such as pre-exposure prophylaxis (PrEP) have been developed to address their HIV risk. Very little consideration, however, has been given to the diversity obscured by 'BMSM' as a category, to how this diversity relates to men's sexual partnering strategies, or to the relevance of these issues for new HIV prevention methods. We conducted a community-based ethnography from June 2013 to May 2014 documenting factors that affect the acceptance of and adherence to PrEP among BMSM. We conducted in-depth interviews with 31 BMSM and 17 community stakeholders, and participant observation. To demonstrate the diversity of social identities, we present a taxonomy of indigenous categories organised along the axes of sexual identity, sexual positioning, and gender performance. We analyse how HIV prevention strategies, such as PrEP, may be more effective if programmes consider how gender, sexuality, and sexual desire shape sexual partnering strategies. This article underlines the importance of attending to the diversity of sexual and social subjectivities among BMSM, of bringing the study of sexuality back into HIV prevention, and of integrating biomedical prevention approaches into community-based programmes. PMID- 26831640 TI - Pseudo-Hydrogen Passivation: A Novel Way to Calculate Absolute Surface Energy of Zinc Blende (111)/(?1 ?1 ?1) Surface. AB - Determining accurate absolute surface energies for polar surfaces of semiconductors has been a great challenge in decades. Here, we propose pseudo hydrogen passivation to calculate them, using density functional theory approaches. By calculating the energy contribution from pseudo-hydrogen using either a pseudo molecule method or a tetrahedral cluster method, we obtained (111)/(111) surfaces energies of Si, GaP, GaAs, and ZnS with high self consistency. This method quantitatively confirms that surface energy is determined by the number and the energy of dangling bonds of surface atoms. Our findings may greatly enhance the basic understandings of different surfaces and lead to novel strategies in the crystal growth. PMID- 26831642 TI - Epilepsy treatment and creativity. AB - Creativity can be defined as the ability to understand, develop, and express, in a systematic fashion, novel orderly relationships. It is sometimes difficult to separate cognitive skills requisite for the creative process from the drive that generates unique new ideas and associations. Epilepsy itself may affect the creative process. The treatment of epilepsy and its comorbidities, by altering or disrupting the same neural networks through antiseizure drugs (ASDs), treatment of epilepsy comorbidities, ablative surgery, or neurostimulation may also affect creativity. In this review, we discuss the potential mechanisms by which treatment can influence the creative process and review the literature on the consequences of therapy on different aspects of creativity in people with epilepsy. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity". PMID- 26831643 TI - In Vitro Pulmonary Cell Culture in Pharmaceutical Inhalation Aerosol Delivery: 2 D, 3-D, and In Situ Bioimpactor Models. AB - BACKGROUND: The use of non-invasive inhaled aerosols for pulmonary drug delivery continues to grow. This is due to the many unique advantages this delivery route offers for the treatment of both local and systemic diseases. The physicochemical properties of the formulated drugs as well as the physiology of the lungs play a key role in both the deposition and absorption of the particles. The airway and the alveolar epithelium are targets for the treatment of respiratory diseases. However, particles have to overcome biological barriers before they reach their target and produce an effect. METHODS: In vitro aerosol dispersion performance (i.e. aerodynamic size and aerodynamic size distribution) of inhalable particles is quantified by inertial impaction, as required by regulatory agencies for an investigational pharmaceutical inhalation aerosol formulation to be approved for use in patients as a marketed pharmaceutical product. Using inertial impaction in conjunction with cell cultures of various pulmonary cells in situ as bioimpactors has unique aspects in correlating aerodynamic properties with pulmonary cellular behavior including viability and uptake. These can be as co-culture or in single culture, as 3-D multicellular spheroids or 2-D cellular monolayer using different conditions to grow them, such as air-liquid interface culture (ALI) or in liquid covered culture (LCC). RESULTS: evaluation of the currently available in vitro models and the challenges in developing reliable cellular tools to predict the deposition of inhalable particles in the lungs as a function of aerodynamic particle properties is presented in the manuscript. CONCLUSION: The mechanistic aerodynamic and biophysical properties of inhaled aerosol particles on the entire respiratory tract at the cellular level based on aerodynamic size and aerodynamic size distribution will be better understood with the development of in vitro methods which are described in this work. PMID- 26831644 TI - Activation of the dsRNA-Activated Protein Kinase PKR in Mitochondrial Dysfunction and Inflammatory Stress in Metabolic Syndrome. AB - BACKGROUND: The double stranded RNA (dsRNA)-activated protein kinase PKR is a well-established protein kinase that is activated by dsRNA during viral infection, and it inhibits global protein synthesis by phosphorylating the alpha subunit of eukaryotic initiation factor 2alpha (eIF2alpha). Recent studies have greatly broadened the recognized physiological activities of PKR by demonstrating its fundamental role in inflammatory signaling, particularly in chronic, low grade inflammation induced by metabolic disorders, known as metaflammation. Metaflammation is initiated by the activation of the NOD-like receptor (NLR), leucine-rich repeat, pyrin domaincontaining 3 (NLRP3) gene by mitochondrial reactive oxygen species (ROS). A protein complex defined as the metaflammasome is assembled in the course of metaflammation. This complex integrates nutritional signaling with cellular stress, inflammatory components, and insulin action and is essential in maintaining metabolic homeostasis. PKR is a key constituent of the metaflammasome and interacts directly with several inflammatory kinases, such as inhibitor kappaB (IkappaB) kinase (IKK) and c-Jun N-terminal kinase (JNK), insulin receptor substrate 1 (IRS1), and component of the translational machinery such as eIF2alpha. CONCLUSION: This review highlights recent findings in PKR mediated metaflammation and its association with the onset of metabolic syndrome in both human and animal models, with a focus on the molecular and biochemical pathways that underlie the progression of obesity, insulin resistance, and type-2 diabetes. PMID- 26831645 TI - Thermostable Subunit Vaccines for Pulmonary Delivery: How Close Are We? AB - In the past century, vaccines have contributed to a significant improvement in global public health by preventing a number of infectious diseases. Despite this, the vaccine field is still facing challenges related to incomplete vaccine coverage and persistent difficult vaccine targets, such as influenza, tuberculosis, and Ebola, for which no good universal vaccines exist. At least two pharmaceutical improvements are expected to help filling this gap: i) The development of thermostable vaccine dosage forms, and ii) the full exploitation of the adjuvant technology for subunit vaccines to potentiate strong immune responses. This review highlights the status and recent advances in formulation and pulmonary delivery of thermostable human subunit vaccines. Such vaccines are very appealing from compliance, distribution and immunological point of view: Being non-invasive, inhalable vaccines are self-administrable, can be distributed independently of functioning freezers and refrigerators, and can be designed to induce mucosal and/or cell-mediated immunity, which is attractive for a number of diseases requiring stimulation of local mucosal immunity for protection. However, the design and delivery of thermostable dry powder-based vaccines represents a technological challenge: It calls for careful formulation and dosage form design, combined with cheap and efficient delivery devices, which must be engineered via a thorough understanding of the physiological barrier and the requirements for induction of mucosal immunity. Here, I review state of the art and perspectives in formulation design and processing methods for powder-based subunit vaccines intended for pulmonary administration, and present dry powder inhaler technologies suitable for translating these vaccines into clinical trials. PMID- 26831646 TI - Mitochondrial Proteases as Emerging Pharmacological Targets. AB - The preservation of mitochondrial function and integrity is critical for cell viability. Under stress conditions, unfolded, misfolded or damaged proteins accumulate in a certain compartment of the organelle, interfering with oxidative phosphorylation and normal mitochondrial functions. In stress conditions, several mechanisms, including mitochondrial unfolded protease response (UPRmt), fusion and fission, and mitophagy are engaged to restore normal proteostasis of the organelle. Mitochondrial proteases are a family of more than 20 enzymes that not only are involved in the UPRmt, but actively participate at multiple levels in the stress-response system. Alterations in their expression levels, or mutations that determine loss or gain of function of these proteases deeply impair mitochondrial functionality and can be associated with the onset of inherited diseases, with the development of neurodegenerative disorders and with the process of carcinogenesis. In this review, we focus our attention on six of them, namely CLPP, HTRA2 and LONP1, by analysing the current knowledge about their functions, their involvement in the pathogenesis of human diseases, and the compounds currently available for inhibiting their functions. PMID- 26831647 TI - What Works to Reduce Victimization? Synthesizing What We Know and Where to Go From Here. AB - While some attention has been paid to "what works" to reduce crime, little is known about the effectiveness of programs designed to reduce victimization. This study systematically reviews 83 program evaluations to identify what works to (a) reduce victimization, (b) enhance beliefs/attitudes about victims, and (c) improve knowledge/awareness of victimization issues. Evidence-based findings are organized around 4 major forms of victimization, including bullying, intimate partner violence, sexual abuse, and other general forms of victimization. Determining whether certain types of programs can reduce the risk of victimization has important implications for improving people's quality of life. Based on our findings, we offer several promising directions for the next generation of research on evaluating victimization programs. The goal of this study is to improve the strength of future program evaluations, replications, and other systematic reviews as researchers and practitioners continue to learn what works to reduce victimization. PMID- 26831648 TI - Biased self-perceived social competence and engagement in subtypes of aggression: Examination of peer rejection, social dominance goals, and sex of the child as moderators. AB - This study expands on prior research suggesting that children who either over- or under-estimate their social competence relative to others' reports are more likely to be aggressive. Linear and curvilinear associations between biased social self-perceptions and forms (physical vs. relational) and functions (proactive vs. reactive) of aggression were tested along with three moderators (peer rejection, social dominance goals, and child sex). Children in the fifth through eight grade (N = 167) completed self-reports of perceived social competence and social dominance goals. Teachers completed ratings of children's social competence, peer rejection, and reactive and proactive physical and relational aggression. Bias in self-perceived social competence was quantified as the residual difference between child and teacher ratings of the child's social competence. There was a significant interaction between quadratic bias and peer rejection predicting reactive physical aggression; rejected children with a positive bias or a negative bias were highest in reactive physical aggression. The interaction between linear bias, social dominance goals, and the sex of the child was also significant when predicting proactive physical aggression. Among girls who highly valued social dominance, a positive bias predicted greater proactive physical aggression. Results are discussed in terms of implications for aggression theory and intervention. Aggr. Behav. 42:498-509, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26831641 TI - Pharmacologic interventions for the prevention and treatment of retinopathy of prematurity. AB - Retinopathy of prematurity (ROP), a significant morbidity in prematurely born infants, is the most common cause of visual impairment and blindness in children and persists till adulthood. Strict control of oxygen therapy and prevention of intermittent hypoxia are the keys in the prevention of ROP, but pharmacologic interventions have decreased risk of ROP. Various drug classes such as methylxanthines (caffeine), VEGF inhibitors, antioxidants, and others have decreased ROP occurrence. The timing of pharmacologic intervention remains unsettled, but early prevention rather than controlling disease progression may be preferred. These drugs act through different mechanisms, and synergistic approaches should be considered to maximize efficacy and safety. PMID- 26831649 TI - Decreased Number of Circulating Endothelial Progenitor Cells (CD133+/KDR+) in Patients with Psoriatic Arthritis. AB - Cardiovascular diseases are a major cause of mortality in patients with psoriatic arthritis (PsA), but the precise mechanism of increased cardiovascular risk is unknown. Endothelial dysfunction plays a crucial role in the development of atherosclerosis. Circulating endothelial progenitor cells (CEPCs) contribute to endothelial regeneration and their level may be affected by chronic inflammation. The aim of this study was to evaluate the number of CEPCs in patients with PsA (n = 24) compared with controls (n = 26). CEPCs were identified as CD133+/ KDR+ cells in peripheral blood, using flow cytometry. A significantly decreased number of CEPCs was observed in patients with PsA (p < 0.0001). The number of these cells was significantly, inversely correlated with the severity of skin and joint involvement (Psoriasis Area and Severity Index (PASI), DAS28) and the level of C reactive protein. We hypothesize that the reduced number of CEPCs may indicate and contribute to the increased cardiovascular risk in patients with PsA. PMID- 26831650 TI - Reduced production of ethyl carbamate for wine fermentation by deleting CAR1 in Saccharomyces cerevisiae. AB - Ethyl carbamate (EC), a pluripotent carcinogen, is mainly formed by a spontaneous chemical reaction of ethanol with urea in wine. The arginine, one of the major amino acids in grape musts, is metabolized by arginase (encoded by CAR1) to ornithine and urea. To reduce the production of urea and EC, an arginase deficient recombinant strain YZ22 (Deltacarl/Deltacarl) was constructed from a diploid wine yeast, WY1, by successive deletion of two CAR1 alleles to block the pathway of urea production. The RT-qPCR results indicated that the YZ22 almost did not express CAR1 gene and the specific arginase activity of strain YZ22 was 12.64 times lower than that of parent strain WY1. The fermentation results showed that the content of urea and EC in wine decreased by 77.89 and 73.78 %, respectively. Furthermore, EC was forming in a much lower speed with the lower urea during wine storage. Moreover, the two CAR1 allele deletion strain YZ22 was substantially equivalent to parental strain in terms of growth and fermentation characteristics. Our research also suggested that EC in wine originates mainly from urea that is produced by the arginine. PMID- 26831652 TI - Prospective, open-label evaluation of a new albuterol multidose dry powder inhaler with integrated dose counter. AB - BACKGROUND: Albuterol multidose dry powder inhaler (MDPI) with an integrated dose counter allows patients to track the number of remaining doses and to simplify dosing by eliminating the need to coordinate inhalation with actuation associated with metered-dose inhalers. OBJECTIVE: To evaluate the functionality, reliability, and accuracy of the albuterol MDPI integrated dose counter in a real world clinical setting. METHODS: This open-label, phase III study enrolled patients ages >=4 years with asthma or chronic obstructive pulmonary disease. Patients who demonstrated adequate MDPI inhaler technique and >=90% compliance with dosing and diary completion during a run-in period qualified for treatment with albuterol MDPI with a dose counter (2 inhalations/dose; 90 MUg/inhalation) twice daily for up to 50 days. Patient-reported counter readings and patient reported actuations were recorded in daily diaries and were used to assess dose counter accuracy. An ease-of-use and satisfaction questionnaire was given at the final visit. RESULTS: A total of 317 patients were enrolled in the study. The dose-cycle undercount (i.e., actuation occurred, but the counter display did not count down) was 2.05 per 200 actuations. The estimated mean +/- standard error absolute value of the total discrepancy size after 200 actuations was 2.07 +/- 0.140. Most patients (83%) were somewhat or very satisfied, and >90% were satisfied with ease of holding and/or handling, using and taking, and inhaling a dose from the device. The albuterol MDPI was generally well tolerated. CONCLUSION: The albuterol MDPI dose counter functioned reliably and accurately. Albuterol MDPI was well tolerated, with a high degree of patient satisfaction in a real-world setting. CLINICAL TRIAL NUMBER: NCT01857323. PMID- 26831651 TI - A novel chimeric prophage vB_LdeS-phiJB from commercial Lactobacillus delbrueckii subsp. bulgaricus. AB - Prophage vB_LdeS-phiJB (phiJB) was induced by mitomycin C and UV radiation from the Lactobacillus delbrueckii subsp. bulgaricus SDMCC050201 isolated from a Chinese yoghurt sample. It has an isometric head and a non-contractile tail with 36,969 bp linear double-stranded DNA genome, which is classified into the group a of Lb. delbrueckii phages. The genome of phiJB is highly modular with functionally related genes clustered together. Unexpectedly, there is no similarity of its DNA replication module to any phages that have been reported, while it consists of open-reading frames homologous to the proteins of Lactobacillus strains. Comparative genomic analysis indicated that its late gene clusters, integration/lysogeny modules and DNA replication module derived from different evolutionary ancestors and integrated into a chimera. Our results revealed a novel chimeric phage of commercial Lb. delbrueckii and will broaden the knowledge of phage diversity in the dairy industry. PMID- 26831653 TI - The Antagonistic Effect of Selenium on Lead-Induced Inflammatory Factors and Heat Shock Protein mRNA Level in Chicken Cartilage Tissue. AB - Selenium (Se) is recognized as a necessary trace mineral in animal diets, including those of birds. Lead (Pb) is a toxic heavy metal and can damage organs in humans and animals. Complex antagonistic interactions between Se and heavy metals have been reported in previous studies. However, little is known regarding the effects of Se on Pb-induced toxicity and the expression of inflammatory factors and heat shock proteins (HSPs) in the cartilage of chickens. In this present study, we fed chickens either with Se or Pb or both Se and Pb supplement and later analyzed the mRNA expressions of inflammatory factors (inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-kappaB), tumor necrosis factor alpha (TNF-alpha), and cyclooxygenase-2 (COX-2)) and HSPs (Hsp27, Hsp40, Hsp60, Hsp70, and Hsp90). The results showed that Se and Pb influenced the expression of inflammatory factors and HSP genes in the chicken cartilage tissues. Additionally, we also found that antagonistic interaction existed between Se and Pb supplementation. Our findings suggested that Se could exert a antagonistic effect on Pb in chicken cartilage tissues. PMID- 26831654 TI - Self-Reported Type 2 Diabetes and Diabetes-Related Eye Disease in Jews and Arabs in Israel. AB - Prevalence rates of diabetes and its complications may be higher in minorities. We assessed these rates in Jews and Arabs living in Israel. Data were pooled from the first and second Israeli national health interview surveys. 9625 Jews and 2401 Arabs participated in the analysis. The age adjusted rate of self-reported diabetes was 10.7 % among Arabs and 5.7 % among Jews [odds ratio (OR) 2.14, 95 % confidence interval 1.77-2.60]. After adjustment for risk factors the OR decreased to 1.28 (95 % CI 1.04-1.59). The rate of self-reported diabetes-related eye disease was 37.6 % among Arabs with diabetes and 18.3 % among Jews (OR 2.69, 95 % CI 1.84-3.93). After adjustment the odds among Arabs were still double that of Jews (OR 2.26, 95 % CI 1.44-3.56). Self-reported type 2 diabetes and diabetes related eye disease were higher among Arabs. Multi-disciplinary and cultural sensitive approach is required in order to improve diabetes care among the Arab population. PMID- 26831655 TI - Focus Group Study of Chinese International Students' Knowledge and Beliefs About HPV Vaccination, Before and After Reading an Informational Pamphlet About Gardasil((r)). AB - An increasing need for Human Papillomavirus (HPV) vaccines in China remains unmet in the mainland and the knowledge and intentions of Chinese youth regarding vaccination is unknown. In the fall of 2013, 44 Chinese international students (CIS) attending a university in the United States Midwest participated in 10 focus group discussions (five female and five male). Result showed that participants have limited awareness and knowledge about HPV infection and vaccination, participants erroneously believed that the causes of cervical cancer are abortion and miscarriage. Participants rely heavily on informal sources such as Chinese-based social media platforms and personal social networks for information on sexually transmitted infections. Sexual cultures and behaviors are perceived differently between CIS born in the 1990s and 1980s. Interestingly, participants' perceived stigma about HPV infection decreased with improving knowledge level during group discussions. In conclusion, HPV vaccine should be further promoted alongside sex education among CIS. PMID- 26831656 TI - Overexpression of MicroRNA-221 is associated with poor prognosis in non-small cell lung cancer patients. AB - The abnormal expression of microRNA-221 was detected in several cancers and some studies had indicated that microRNA-221 was associated with cancer prognosis. This study was aimed to evaluate the prognostic significance of microRNA-221 in non-small cell lung cancer (NSCLC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used for detecting the relative expression levels of microRNA-221 in the pathological tissues and corresponding normal tissues of 104 NSCLC patients. The relationship between the expression levels and the clinical features was estimated by Chi-square method and the overall survival of patients at different expression levels was demonstrated by Kaplan-Meier method. Cox regression analysis was used to evaluate the prognostic significance of microRNA 221. The relative expression levels of microRNA-221 in the pathological tissues were remarkably higher than that in the corresponding normal tissues (1.71 vs 1.07, P = 0.000). The expression level was associated with lymph node metastasis (P = 0.001). The results of Kaplan-Meier method indicated that patients with high expression level of microRNA-221 had shorter overall survival time than those with low expression level (36.8 vs 45.2 months, P = 0.001). Moreover, Cox regression analysis suggested that microRNA-221 was a useful independent biomarker for NSCLC prognosis (HR = 1.873, 95 % CI = 1.267-2.768, P = 0.002). The aberrant expression of microRNA-221 is associated with NSCLC progression and it might be a potential biomarker for NSCLC prognosis. PMID- 26831657 TI - Profiling cell-free and circulating miRNA: a clinical diagnostic tool for different cancers. AB - Effective cancer management depends on early diagnosis and treatment. There are several microRNAs (miRNAs) which are used for detection of various cancers. Cell free and circulating miRNAs originate from plasma, either from blood cells or endothelial cells. Cell-free and circulating miRNAs are very much important in the diagnosis and prognosis of cancer therapy. Admittedly, biological knowledge of extracellular miRNAs is still at its preliminary level. Recent discoveries of novel cell-free and circulating miRNAs from the body fluids are now being considered as important biomarkers that may help us in the early diagnosis of any cancer. In the present review, we highlight the biogenesis of miRNAs and their current extracellular pattern, the discovery of circulating miRNA, significant advantages, and different profiling techniques. Finally, we discuss the different circulating miRNAs such as miR-21, miR-20a, miR-155, miR-221, miR-210, miR-218, miR-200-family, miR-141, miR-122, miR-486-5p, miR-423-5p, miR-29a, and miR-500 for clinical diagnosis of various cancers. The present review may be beneficial for future researches concerned with miRNAs which are used for detection of various cancers. PMID- 26831658 TI - Cyclin Y regulates the proliferation, migration, and invasion of ovarian cancer cells via Wnt signaling pathway. AB - This study is designated to investigate the roles of cyclin Y (CCNY) and Wnt signaling pathway in regulating ovarian cancer (OC) cell proliferation, migration, and invasion. Quantitative real-time PCR (qRT-PCR), Western blot, MTT assay, cell scratch, and transwell test were used in our study, and transplanted tumor model was constructed on nude mice. C-Myc, cyclin D1, PFTK1, ki67, OGT, and beta-catenin protein expressions in tumor tissues were detected. CCNY was significantly upregulated in OC cell lines and tissues (both P < 0.05); significant association was observed between CCNY expression and clinicopathological stage, lymph node metastasis (LNM) (P < 0.05); and the CCNY expression in stages III to IV was higher than that in stages I to II, and patients with LNM had higher CCNY expression when compared with those in patients without LNM (P < 0.05); expressions of c-Myc, cyclin D, PFTK1, ki67, and OGT were upregulated in OC tissues compared with ovarian benign tissues, suggesting that these expressions were significantly different between the two groups (P < 0.05); CCNY significantly exacerbated proliferation, migration, and invasion of A2780 cells; c-Myc and cyclin D1 protein expressions increased as the expression of CCNY increased (P < 0.001); beta-catenin expressions in A2780 cells with over expression of CCNY were significantly increased in the nucleus, but significantly decreased in the cytoplasm (both P < 0.05); high expressions of CCNY exacerbated the proliferation of A2780 cells in nude mice and significantly increased c-Myc, cyclin D1, PFTK1, ki67, and OGT protein expressions in tumor tissues which were transplanted into nude mice (P < 0.01). CCNY might exacerbate the proliferation, migration, and invasion of OC cells via activating the Wnt signaling pathway. Thus, this study provides a theoretical foundation for the development of therapeutic drugs that are able to cure OC by targeting CCNY. PMID- 26831659 TI - Milky spots: omental functional units and hotbeds for peritoneal cancer metastasis. AB - As the most common metastatic disease of abdomen pelvic cavity cancer, peritoneal carcinomatosis (PC) renders significant negative impact on patient survival and quality of life. Invasive peritoneal exfoliated cancer cells (PECCs) preferentially select the omentum as a predominant target site for cancer cell colonization and proliferation compared with other tissues in the abdominal cavity. The precise pathogenic mechanism remains to be determined. As omental milky spots (MSs) are the major implantation site for malignant cells in peritoneal dissemination, researches on mechanisms of PC have been mainly focused on MS, primitive lymphoid tissues with unique structural features, and functional characteristics. To date, extensive biophysical and biochemical methods have been manipulated to investigate the MS exact function in the peritoneal cavity. This review summarized MS as hotbeds for PECC. The anatomical distribution was briefly described first. Then, MS histology was systematically reviewed, including morphological features, cellular constituents, and histological staining methods. At last, the roles of MS in PC pathological process were summarized with special emphasis on the distinct roles of macrophages. PMID- 26831660 TI - Differential blood-based diagnosis between benign prostatic hyperplasia and prostate cancer: miRNA as source for biomarkers independent of PSA level, Gleason score, or TNM status. AB - Since the benefit of prostate-specific antigen (PSA) screening remains controversial, new non-invasive biomarkers for prostate carcinoma (PCa) are still required. There is evidence that microRNAs (miRNAs) in whole peripheral blood can separate patients with localized prostate cancer from healthy individuals. However, the potential of blood-based miRNAs for the differential diagnosis of PCa and benign prostatic hyperplasia (BPH) has not been tested. We compared the miRNome from blood of PCa and BPH patients and further investigated the influence of the tumor volume, tumor-node-metastasis (TNM) classification, Gleason score, pretreatment risk status, and the pretreatment PSA value on the miRNA pattern. By microarray approach, we identified seven miRNAs that were significantly deregulated in PCa patients compared to BPH patients. Using quantitative real time PCR (qRT-PCR), we confirmed downregulation of hsa-miR-221* (now hsa-miR-221 5p) and hsa-miR-708* (now hsa-miR-708-3p) in PCa compared to BPH. Clinical parameters like PSA level, Gleason score, or TNM status seem to have only limited impact on the overall abundance of miRNAs in patients' blood, suggesting a no influence of these factors on the expression of deregulated miRNAs. PMID- 26831661 TI - Effect of Shenfu injection on immune function of mice bearing Lewis lung sarcoma with chemotherapy. AB - Chemotherapy damages immune system and has a lot of side effects. In this study, we investigate the function of Shenfu injection to reduce these unfavorable effects induced by chemotherapy on mice bearing Lewis lung sarcoma. Mice inoculated with Lewis lung sarcoma cells were divided into five groups: Lewis lung sarcoma control group, cyclophosphamide (CTX) group, and Shenfu injection (high, moderate, and low dose) + CTX group. After a 14-day treatment, the counting of peripheral blood cells, CD3+, CD4+, and CD8+ T lymphocytes were done, immunoglobulin (Ig) was measured, coefficients of spleen and thymus were calculated, and spleen T cell proliferation was evaluated in vitro. The CD4+/CD8+ and CD3+ T cells in high- and moderate-dose Shenfu groups were more than the CTX group (p < 0.05); spleen T cell proliferation of mice in high-dose Shenfu + CTX group is more prominent than the CTX group (p < 0.05); coefficients of spleen and thymus, WBC, and platelet (PLT) counting of mice in the CTX group were lower than control and high and moderate dose Shenfu + CTX groups. The level of serous IgG and IgM of all test groups shows no significant difference. Shenfu injection can improve cellular immune function and reduce myolosuppression of mice delivered with chemotherapy. PMID- 26831663 TI - Clinical significance of fibroblast growth factor receptor 2 expression in patients with residual rectal cancer after preoperative chemoradiotherapy: relationship with KRAS or BRAF mutations and MSI status. AB - This study was designed to determine the prognostic impact and clinical significance of FGFR2 in residual disease after preoperative chemoradiotherapy (CRT) in patients with rectal cancer. The surgical specimens of 145 patients with residual rectal cancer after preoperative CRT were analyzed. To evaluate FGFR2 expression, immunohistochemistry was performed on whole section tissues. KRAS exon 2 (codon 12 and 13), BRAF V600E mutational status, and microsatellite instability (MSI) were determined using polymerase chain reactions. Of the eligible 141 patients, FGFR2 over-expression was observed in 75.9 % (n = 107) and was correlated with perineural invasion (P = 0.005) and inferior tumor regression grading (TRG) (P = 0.009). However, FGFR2 expression had no relationship with KRAS and BRAF mutation results or with MSI results. On univariate analysis, FGFR2 over-expression was significantly associated with worse rectal cancer-specific survival (RCSS) (P = 0.005) and disease-free survival (DFS) (P = 0.035). However, multivariate analysis revealed that FGFR2 over-expression was not independently associated with RCSS and DFS (all P > 0.05). Although FGFR2 over-expression did not independently influence patient outcome, FGFR2 over-expression was associated with worse prognosis and inferior TRG. Our data may aid in understanding the therapeutic approaches targeting FGFR2 in patients with residual rectal cancer after preoperative CRT. PMID- 26831662 TI - Potential risk of esophageal squamous cell carcinoma due to nucleotide excision repair XPA and XPC gene variants and their interaction among themselves and with environmental factors. AB - The association of nucleotide excision repair (NER) gene polymorphisms with esophageal squamous cell carcinoma (ESCC) is inconclusive. The aim of the current study was to assess the association of repair gene xeroderma pigmentosum A (XPA) (rs-1800975) and xeroderma pigmentosum C (XPC) (rs-2228000) polymorphisms with ESCC risk as well as modifying effects of environmental factors. The genotyping was done in 450 confirmed ESCC cases and equal number of individually matched controls by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and direct sequencing methods. Conditional logistic regression models were used to assess the genotypic associations and interactions. A high ESCC risk was found in subjects who carried the homozygous minor allele of XPA (odds ratio (OR) = 3.57; 95 % confidence interval (CI) = 1.76 7.23), and the risk was higher when analysis was limited to participants who were ever smokers (OR = 4.22; 95 % CI = 2.01-8.88), lived in adobe houses (OR = 8.42; 95 % CI = 3.74-18.95), consumed large volumes of salt tea (OR = 7.42; 95 % CI = 3.30-16.69), or had a positive family history of cancer (FHC) (OR = 9.47; 95 % CI = 4.67-19.20). In case of XPC, a homozygous minor allele also showed strong association with ESCC risk (OR = 4.43; 95 % CI = 2.41-8.16). We again observed a very strong effect of the above environmental factors in elevating the risk of ESCC. Further, the variant genotypes of both genes in combination showed an increased risk towards ESCC (OR = 7.01; 95 % CI = 3.14-15.64) and such association was synergistically significant. Salt tea consumption showed an interaction with genotypes of XPA and XPC. However, an interaction with FHC was significant in the case of XPA genotype only. XPA and XPC genotypes are associated with an increased risk of ESCC, and such association was reasonably modulated by different exposures. PMID- 26831664 TI - Glutathione S-transferase M1 null genotype related to poor prognosis of colorectal cancer. AB - Published studies showed controversial findings about the relationship between glutathione S-transferase M1 (GSTM1) null genotype and clinical outcomes of patients with colorectal cancer. We performed a meta-analysis to quantitatively assess the association between GSTM1 null genotype and prognosis of patients with colorectal cancer. We systematically searched Pubmed, Embase, and Web of Science to identify prospective or retrospective cohort studies assessing the association of GSTM1 null genotype with overall survival (OS) or disease-free survival (DFS) in colorectal cancer. The hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) were used to assess the association of GSTM1 null genotype with OS or DFS. Finally, 15 studies from 14 publications with 4326 colorectal cancer patients were included into the meta-analysis. There was no heterogeneity in the meta analysis relating OS (I (2) = 0 %) and DFS (I (2) = 0 %). Overall, GSTM1 null genotype was significantly associated with poor OS in patients with colorectal cancer (HR = 1.18, 95 % CI 1.07-1.30, P = 0.001). In addition, GSTM1 null genotype was also significantly associated with poor DFS in patients with colorectal cancer (HR = 1.15, 95 % CI 1.03-1.28, P = 0.015). No obvious risk of publication bias was observed. GSTM1 null genotype is significantly associated with poor OS and DFS in patients with colorectal cancer, which suggests that GSTM1 null genotype confers poor effect on the prognosis of colorectal cancer. PMID- 26831665 TI - DNA methylation status defines clinicopathological parameters including survival for patients with clear cell renal cell carcinoma (ccRCC). AB - Epigenetic alterations in the methylome have been associated with tumor development and progression in renal cell carcinoma (RCC). In this study, 45 tumor samples, 12 tumor-free kidney cortex tissues, and 24 peripheral blood samples from patients with clear cell RCC (ccRCC) were analyzed by genome-wide promoter-directed methylation arrays and related to clinicopathological parameters. Unsupervised hierarchical clustering separated the tumors into two distinct methylation groups (clusters A and B), where cluster B had higher average methylation and increased number of hypermethylated CpG sites (CpGs). Furthermore, tumors in cluster B had, compared with cluster A, a larger tumor diameter (p = 0.033), a higher morphologic grade (p < 0.001), a higher tumor-node metastasis (TNM) stage (p < 0.001), and a worse prognosis (p = 0.005). Higher TNM stage was correlated to an increase in average methylation level (p = 0.003) and number of hypermethylated CpGs (p = 0.003), whereas a number of hypomethylated CpGs were mainly unchanged. However, the predicted age of the tumors based on methylation profile did not correlate with TNM stage, morphological grade, or methylation cluster. Differently methylated (DM) genes (n = 840) in ccRCC samples compared with tumor-free kidney cortex samples were predominantly hypermethylated and a high proportion were identified as polycomb target genes. The DM genes were overrepresented by transcription factors, ligands, and receptors, indicating functional alterations of significance for ccRCC progression. To conclude, increased number of hypermethylated genes was associated with increased TNM stage of the tumors. DNA methylation classification of ccRCC tumor samples at diagnosis can serve as a clinically applicable prognostic marker in ccRCC. PMID- 26831666 TI - MicroRNA-7 downregulates the oncogene VDAC1 to influence hepatocellular carcinoma proliferation and metastasis. AB - Recent studies have been shown that voltage-dependent anion channel 1 (VDAC1) plays an important role in carcinogenesis. However, its molecular biological function in hepatocellular carcinoma (HCC) has not been entirely clarified. This study investigated the expression of VDAC1 in HCC and its prognostic value for HCC patients. Furthermore, we also identify the relevant VDAC1 direct target. Western blot, real-time quantitative PCR (qRT-PCR), and immunohistochemical (IHC) staining were performed to detect the expression of VDAC1 in HCC. Furthermore, the relationship between the VDAC1 level and clinicopathological features and prognostic values was explored. The effects of VDAC1 on HCC cell proliferation, migration, and invasion were also investigated in vitro. Predicted target gene of VDAC1 was determined by dual-luciferase reporter assay, qRT-PCR, and Western blot analyses. Our results revealed elevated VDAC1 messenger RNA (mRNA) (P = 0.0020) and protein (P = 0.0035) expression in tumor tissue samples compared with paired adjacent non-tumorous tissue samples. High VDAC1 expression was correlated with distant metastasis (P = 0.025), differentiation (P = 0.002), and advanced tumor stage (P = 0.004) in HCC patients. Kaplan-Meier survival analysis demonstrated that high expression of VDAC1 was significantly correlated with a poor prognosis for HCC patients (P < 0.001). The multivariate analysis revealed that VDAC1 expression was an independent prognostic factor of the overall survival rate of HCC patients. Furthermore, knockdown of VDAC1 inhibits HCC cell proliferation, migration, and invasion in vitro. Moreover, further study revealed that miR-7 was a putative target of VDAC1. Our study suggested that miR-7 suppressed the expression of VDAC1. VDAC1 plays an important role in tumor progression and may be used as a potential role in the prognosis of HCC patients. PMID- 26831668 TI - Pre-clinical characterization of 4SC-202, a novel class I HDAC inhibitor, against colorectal cancer cells. AB - Histone deacetylase (HDAC) overactivity in colorectal cancer (CRC) promotes cancer progression. In the current study, we showed that 4SC-202, a novel class I HDAC inhibitor (HDACi), potently inhibited survival and proliferation of primary human colon cancer cells and established CRC lines (HT-29, HCT-116, HT-15, and DLD-1). Yet, the same 4SC-202 treatment was non-cytotoxic to colon epithelial cells where HDAC-1/-2 expressions were extremely low. 4SC-202 provoked apoptosis activation in CRC cells, while caspase inhibitors (z-VAD-CHO and z-DVED-CHO) significantly alleviated 4SC-202-exerted cytotoxicity in CRC cells. Meanwhile, 4SC-202 induced dramatic G2-M arrest in CRC cells. Further studies showed that AKT activation might be an important resistance factor of 4SC-202. 4SC-202 induced cytotoxicity was dramatically potentiated with serum starvation, AKT inhibition (by perifosine or MK-2206), or AKT1-shRNA knockdown in CRC cells. On the other hand, exogenous expression of constitutively active AKT1 (CA-AKT1) decreased the sensitivity by 4SC-202 in HT-29 cells. Notably, 4SC-202, at a low concentration, enhanced oxaliplatin-induced in vitro anti-CRC activity. In vivo, we showed that oral gavage of 4SC-202 inhibited HT-29 xenograft growth in nude mice, and when combined with oxaliplatin, its activity was further strengthened. Together, these pre-clinical results indicate that 4SC-202 may be further investigated as a valuable anti-CRC agent/chemo-adjuvant. PMID- 26831667 TI - Kaempferol inhibits cell proliferation and glycolysis in esophagus squamous cell carcinoma via targeting EGFR signaling pathway. AB - Antitumor activity of kaempferol has been studied in various tumor types, but its potency in esophagus squamous cell carcinoma is rarely known. Here, we reported the activity of kaempferol against esophagus squamous cell carcinoma as well as its antitumor mechanisms. Results of cell proliferation and colony formation assay showed that kaempferol substantially inhibited tumor cell proliferation and clone formation in vitro. Flow cytometric analysis demonstrated that tumor cells were induced G0/G1 phase arrest after kaempferol treatment, and the expression of protein involved in cell cycle regulation was dramatically changed. Except the potency on cell proliferation, we also discovered that kaempferol had a significant inhibitory effect against tumor glycolysis. With the downregulation of hexokinase-2, glucose uptake and lactate production in tumor cells were dramatically declined. Mechanism studies revealed kaempferol had a direct effect on epidermal growth factor receptor (EGFR) activity, and along with the inhibition of EGFR, its downstream signaling pathways were also markedly suppressed. Further investigations found that exogenous overexpression of EGFR in tumor cells substantially attenuated glycolysis suppression induced by kaempferol, which implied that EGFR also played an important role in kaempferol mediated glycolysis inhibition. Finally, the antitumor activity of kaempferol was validated in xenograft model and kaempferol prominently restrained tumor growth in vivo. Meanwhile, dramatic decrease of EGFR activity and hexokinase-2 expression were observed in kaempferol-treated tumor tissue, which confirmed these findings in vitro. Briefly, these studies suggested that kaempferol, or its analogues, may serve as effective candidates for esophagus squamous cell carcinoma management. PMID- 26831669 TI - Trichostatin A potentiates TRAIL-induced antitumor effects via inhibition of ERK/FOXM1 pathway in gastric cancer. AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an ideal apoptosis inducer and believed to have promise in cancer therapy, yet part of cancer cells exhibit resistance to TRAIL-mediated apoptosis. This necessitates the exploration of agents that resensitizes cancer cells to TRAIL. In our study, we found that Trichostatin A (TSA), an histone deacetylase (HDAC) inhibitor, augmented TRAIL-induced apoptosis in gastric cancer cells in a caspase-dependent manner. Besides, upregulation of DR5 and downregulation of anti-apoptotic proteins including XIAP, Mcl-1, Bcl-2 and Survivin also contributed to this synergism. Noticeably, TSA treatment inhibited Forkhead boxM1 (FOXM1), which expression level showed negative correlation with TRAIL sensitivity. Similarly, silencing of FOXM1 by small interfering RNA (siRNA) resensitized cancer cells to TRAIL and strengthened the TRAIL-augmenting effect of TSA. In addition, we demonstrated the depletion of FOXM1 was a consequence of the inactivation of ERK mediated by TSA. Collectively, it was first shown that TSA potentiated TRAIL sensitivity via ERK/FOXM1 pathway in gastric cancer cells. FOXM1 might serve as a biomarker for predicting sensitivity to TRAIL. PMID- 26831670 TI - Photopic negative response of full-field electroretinography in patients with different stages of glaucomatous optic neuropathy. AB - PURPOSE: To evaluate photopic negative response (PhNR) discrimination ability between healthy and glaucomatous patients. METHODS: Ninety eyes of 50 patients with primary open angle glaucoma (POAG) and 45 eyes of 23 healthy age- and sex matched controls were investigated. Based on European Glaucoma Society criteria, POAG patients were divided into three groups: early, moderate and advanced glaucoma. Following measurements were analysed: mean defect (MD) from Humphrey Visual Field Analyzer, SITA standard 24-2 white on white perimetry; nerve fibre index (NFI) obtained from scanning laser polarimetry; and GDx and PhNR amplitude and PhNR/b-wave ratio. PhNR was elicited by red stimuli with flash strength of 1.6 cd s/m(2) on blue background of 25 cd/m(2). Correlations between retinal ganglion cells function (PhNR), retinal sensitivity (MD) and structure (NFI) were calculated. Sensitivity and specificity of PhNR parameters were calculated with standard formulas. Receiver operating characteristic (ROC) curves were used to determine optimal cut-off values. The area under the curve (AUC) was used to compare the ROC curves results between PhNR amplitude and ratio. RESULTS: PhNR amplitude and ratio were significantly reduced in early, moderate and advanced glaucoma groups compared to controls. The sensitivity and specificity to detect glaucoma in early POAG were equal to 53.3 and 90.0% for PhNR amplitude and 60.0 and 70.0% for PhNR ratio; in moderate POAG 63.3 and 80.0% for PhNR amplitude and 60.0 and 86.7% for PhNR ratio; and in advanced POAG 76.6 and 80.0% for PhNR amplitude, 90.0 and 73.3% for PhNR ratio. There were no significant differences between AUC for PhNR amplitude (0.76-0.86) and PhNR ratio (0.78-0.86), p > 0.05. PhNR amplitudes and ratios correlated significantly with MD measured by SAP and NFI obtained from GDx (p < 0.05). PhNR amplitude significantly decreases with advancement of visual field defects in glaucoma patients. CONCLUSIONS: PhNR reveals dysfunction of RGCs in early, moderate and advanced stage of POAG. PhNR has good discrimination ability in detecting glaucomatous patients. PhNR might be a useful test in glaucoma diagnosis. PMID- 26831671 TI - Use of extracorporeal carbon dioxide removal (ECCO2R) in 239 intensive care units: results from a French national survey. PMID- 26831672 TI - Continuous infusion of beta-lactam antibiotics for all critically ill patients? PMID- 26831673 TI - Lactate-guided resuscitation saves lives: no. PMID- 26831674 TI - Lactate-guided resuscitation saves lives: yes. PMID- 26831675 TI - Lactate-guided resuscitation saves lives: we are not sure. PMID- 26831678 TI - Two- and three-dimensional transoesophageal echocardiography in large swine used as model for transcatheter heart valve therapies: standard planes and values. AB - OBJECTIVES: Swine models are widely used to develop new techniques and materials for the treatment of heart valve disease like aortic valve and mitral valve transcatheter interventions and to train physicians in these techniques. Transoesophageal echocardiography (TOE) is crucial in these models. We defined standard planes of 2D and 3D TOE in healthy pigs undergoing transcatheter heart valve interventions. METHODS: Twenty healthy pigs (weight 56-106 kg) underwent different mitral and aortic valve interventions (transcatheter aortic valve implantations, implantations of a mitral band, bicuspidization of the aortic valve, trans-septal punctures). For image guidance of the procedures, an adult TOE probe was introduced under direct vision in the oesophagus. Before the procedure itself was performed, a standardized protocol was used to determine normal values for anatomical and functional echocardiographic parameters. RESULTS: Positioning of the probe was possible in all animals and ideal when achieving a distance from the front teeth (incisors) of 40-60 cm. Anteflexion and lateroflexion of the probe was necessary to achieve optimal imaging quality. 2D visualization of all relevant cardiac structures was possible. The aortic annulus diameter was 24.1 +/- 2.5 mm, the sinus of valsalva diameter was 30.6 +/- 4 mm and the sinotubular junction diameter was 25.2 +/- 4 mm. The ascending aorta had a diameter of 24 +/- 4 mm and the descending aorta a diameter of 16 +/- 5 mm. The mitral valve anterior-posterior diameter was 31.8 +/- 4 mm and the commissure to commissure diameter was 40.5 +/- 5 mm resulting in a mitral valve area of 10.7 +/ 1.5 cm(2). 3D visualization was possible for the aortic and the mitral valve. None of the animals showed any pathology except one that had a dilated left ventricle and moderate mitral valve insufficiency. Left and right ventricular dimensions and the anatomy of the aortic-, mitral-, tricuspid and pulmonary valve as well as of the aorta were comparable with those of the human anatomy. CONCLUSIONS: 2D and 3D TOE can be routinely applied as image guidance in pigs used as a model for the development and training of new techniques to treat heart valve disease. PMID- 26831677 TI - Comparison of high glucose concentration blood and crystalloid cardioplegia in paediatric cardiac surgery: a randomized clinical trial. AB - OBJECTIVES: This study investigates the effects of high glucose content on patients undergoing cold crystalloid versus cold blood cardioplegia in terms of early clinical results, functional myocardial recovery and ischaemia-reperfusion injury in patients undergoing repair of acyanotic cardiac lesions. METHODS: Patients were randomly assigned to receive either crystalloid (n = 31) or blood cardioplegia (n = 31). Early clinical results were assessed. Changes in left ventricular fractional shortening, arterial blood lactate levels, central venous saturation, cardiac Troponin I release and blood glucose concentration were measured during the first 24 h after ischaemia. RESULTS: There was no significant difference in clinical outcomes and postoperative complication rates between groups. The postoperative changes in left ventricular function, lactate levels, central venous saturation and Troponin I were not significantly different between groups. The use of crystalloid cardioplegia was associated with significant increases in serum glucose compared with blood cardioplegia. CONCLUSIONS: A high glucose content blood cardioplegia does not show any advantage compared with crystalloid cardioplegia in terms of clinical outcomes, functional recovery and the degree of ischaemic injury in infants and children undergoing repair of acyanotic heart lesions. High glucose concentration of the cardioplegic solution might potentiate ischaemia-reperfusion injury and diminish the beneficial effects of blood cardioplegia. PMID- 26831679 TI - Respiratory manifestations and management in children with Common Variable Immunodeficiency. AB - Common variable immunodeficiency is an antibody deficiency that usually presents in childhood with recurrent sino-pulmonary infections. Diagnostic delay is frequent and thus respiratory morbidity is common, ranging from recurrent suppurative bronchitis to bronchiectasis. Immunoglobulin replacement therapy is the mainstay of treatment, whilst prophylactic antibiotic therapy and muco ciliary clearance are additional treatment options. This review examines the diagnosis and management of respiratory issues in children with CVID. PMID- 26831676 TI - Ultrasound-guided percutaneous dilational tracheostomy versus bronchoscopy-guided percutaneous dilational tracheostomy in critically ill patients (TRACHUS): a randomized noninferiority controlled trial. AB - PURPOSE: Percutaneous dilational tracheostomy (PDT) is routinely performed in the intensive care unit with bronchoscopy guidance. Recently, ultrasound has emerged as a potentially useful tool to assist PDT and reduce procedure-related complications. METHODS: An open-label, parallel, non-inferiority randomized controlled trial was conducted comparing an ultrasound-guided PDT with a bronchoscopy-guided PDT in mechanically ventilated critically ill patients. The primary outcome was procedure failure, defined as a composite end-point of conversion to a surgical tracheostomy, unplanned associated use of bronchoscopy or ultrasound during PDT, or the occurrence of a major complication. RESULTS: A total of 4965 patients were assessed for eligibility. Of these, 171 patients were eligible and 118 underwent the procedure, with 60 patients randomly assigned to the ultrasound group and 58 patients to the bronchoscopy group. Procedure failure occurred in one (1.7%) patient in the ultrasound group and one (1.7%) patient in the bronchoscopy group, with no absolute risk difference between the groups (90% confidence interval, -5.57 to 5.85), in the "as treated" analysis, not including the prespecified margin of 6% for noninferiority. No other patient had any major complication in either group. Procedure-related minor complications occurred in 20 (33.3%) patients in the ultrasound group and in 12 (20.7%) patients in the bronchoscopy group (P = 0.122). The median procedure length was 11 [7-19] vs. 13 [8-20] min (P = 0.468), respectively, and the clinical outcomes were also not different between the groups. CONCLUSIONS: Ultrasound-guided PDT is noninferior to bronchoscopy-guided PDT in mechanically ventilated critically ill patients. PMID- 26831680 TI - Metal-Multilayer-Dielectric Structure for Enhancement of s- and p-Polarized Evanescent Waves. AB - We propose a structure based on combination of multilayer stack of dielectric films and thin metal layer for excitation and enhancement of both s- and p polarized evanescent waves. It is shown that two different mechanisms of evanescent wave excitation may occur at the same angle of light beam incidence on the structure. Application for evanescent wave polarization holographic recording with the help of this structure is discussed. PMID- 26831682 TI - Structural Transformations in Austenitic Stainless Steel Induced by Deuterium Implantation: Irradiation at 295 K. AB - Deuterium thermal desorption spectra were investigated on the samples of austenitic steel 18Cr10NiTi pre-implanted at 295 K with deuterium ions in the dose range from 8 * 10(14) to 2.7 * 10(18) D/cm(2). The kinetics of structural transformation development in the steel layer was traced from deuterium thermodesorption spectra as a function of deuterium concentration. Three characteristic regions with different low rates of deuterium amount desorption as the implantation dose increases were revealed: I-the linear region of low implantation doses (up to 1 * 10(17) D/cm(2)); II-the nonlinear region of medium implantation doses (1 * 10(17) to 8 * 10(17) D/cm(2)); III-the linear region of high implantation doses (8 * 10(17) to 2.7 * 10(18) D/cm(2)). During the process of deuterium ion irradiation, the coefficient of deuterium retention in steel varies in discrete steps. Each of the discrete regions of deuterium retention coefficient variation corresponds to different implanted-matter states formed during deuterium ion implantation. The low-dose region is characterized by formation of deuterium-vacancy complexes and solid-solution phase state of deuterium in the steel. The total concentration of the accumulated deuterium in this region varies between 2.5 and 3 at.%. The medium-dose region is characterized by the radiation-induced action on the steel in the presence of deuterium with the resulting formation of the energy-stable nanosized crystalline structure of steel, having a developed network of intercrystalline boundaries. The basis for this developed network of intercrystalline boundaries is provided by the amorphous state, which manifests itself in the thermodesorption spectra as a widely temperature-scale extended region of deuterium desorption (structure formation with a varying activation energy). The total concentration of the accumulated deuterium in the region of medium implantation doses makes 7 to 8 at.%. The resulting structure shows stability against the action of deuterium ion implantation. This manifests itself in a nearly complete ceasing of deuterium accumulation from a newly implanted dose (radiation-resistant structure). PMID- 26831681 TI - Effect of Graphene Oxide on the Properties of Porous Silicon. AB - We studied an effect of the graphene oxide (GO) layer on the optical and electrical properties of porous silicon (PS) in hybrid PS-GO structure created by electrochemical etching of silicon wafer and deposition of GO from water dispersion on PS. With the help of scanning electron microscopy (SEM), atomic force microscopy (AFM), and Fourier transform infrared (FTIR) spectroscopy, it was established that GO formed a thin film on the PS surface and is partly embedded in the pores of PS. A comparative analysis of the FTIR spectra for the PS and PS-GO structures confirms the passivation of the PS surface by the GO film. This film has a sufficient transparency for excitation and emission of photoluminescence (PL). Moreover, GO modifies PL spectrum of PS, shifting the PL maximum by 25 nm towards lower energies. GO deposition on the surface of the porous silicon leads to the change in the electrical parameters of PS in AC and DC modes. By means of current-voltage characteristics (CVC) and impedance spectroscopy, it is shown that the impact of GO on electrical characteristics of PS manifests in reduced capacitance and lower internal resistance of hybrid structures. PMID- 26831683 TI - Carbon- and Binder-Free NiCo2O4 Nanoneedle Array Electrode for Sodium-Ion Batteries: Electrochemical Performance and Insight into Sodium Storage Reaction. AB - Sodium (Na)-ion batteries (NIBs) have attracted significant interest as an alternative chemistry to lithium (Li)-ion batteries for large-scale stationary energy storage systems. Discovering high-performance anode materials is a great challenge for the commercial success of NIB technology. Transition metal oxides with tailored nanoarchitectures have been considered as promising anodes for NIBs due to their high capacity. Here, we demonstrate the fabrication of a nanostructured oxide-only electrode, i.e., carbon- and binder-free NiCo2O4 nanoneedle array (NCO-NNA), and its feasibility as an anode for NIBs. Furthermore, we provide an in-depth experimental study of the Na storage reaction (sodiation and desodiation) in NCO-NNA. The NCO-NNA electrode is fabricated on a conducting substrate by a hydrothermal method with subsequent heat treatment. When tested in an electrochemical Na half-cell, the NCO-NNA electrode exhibits excellent Na storage capability: a charge capacity as high as 400 mAh g(-1) is achieved at a current density of 50 mA g(-1). It also shows a greatly improved cycle life (~215 mAh g(-1) after 50 cycles) in comparison to a conventional powder-type electrode (~30 mAh g(-1)). However, the Na storage performance is still inferior to that of Li, which is mainly due to sluggish kinetics of sodiation-desodiation accompanied by severe volume change. PMID- 26831684 TI - Dispersion Polymerization of Polystyrene Particles Using Alcohol as Reaction Medium. AB - In this study, monodisperse polystyrene nanospheres were prepared by dispersion polymerization using alcohol as reaction medium to prepare colloidal clusters of the latex beads. Polyvinylpyrrolidone (PVP) and 2 (methacryloyloxy)ethyltrimethylammonium chloride (MTC) were used as dispersion stabilizer and comonomer, respectively. The particle size could be controlled by adjusting the reactant compositions such as the amount of stabilizer, comonomer, and water in the reactant mixture. The size and monodispersity of the polymeric particles could be also controlled by changing the reaction medium with different alcohols other than ethanol or adjusting the polymerization temperature. The synthesized particles could be self-organized inside water-in-oil emulsion droplets by evaporation-driven self-assembly to produce colloidal clusters of the polymeric nanospheres. PMID- 26831686 TI - Nanoparticle Near-Surface Electric Field. AB - Theoretical studies show that surface reconstruction in some crystals involves splitting the surface atomic layer into two-upper and lower-sublayers consisting of atoms with only positive or only negative effective electric charges, respectively. In a macroscopic crystal with an almost infinite surface, the electric field induced by such a surface-dipole is practically totally concentrated between the sublayers. However, when the material is powdered and its particles are of sufficiently small sizes, an electric field of a significant magnitude can be induced outside the sublayers as well. We have calculated the distribution of the electric field and its potential induced at the surface of a disc-shaped particle. The suggested novel nanoscale effect explains the increase in physical reactivity of nanopowders with decreasing particle sizes. PMID- 26831685 TI - Effects of Annealing on GaAs/GaAsSbN/GaAs Core-Multi-shell Nanowires. AB - The effects of ex-situ annealing in a N2 ambient on the properties of GaAs/GaAsSbN/GaAs core-multi-shell nanowires on Si (111) substrate grown by self catalyzed molecular beam epitaxy (MBE) are reported. As-grown nanowires exhibit band edge emission at ~0.99 eV with a shoulder peak at ~0.85 eV, identified to arise from band tail states. A large red shift of 7 cm(-1) and broadened Raman spectra of as-grown nanowires compared to that of non-nitride nanowires confirmed phonon localization at N-induced localized defects. On annealing nanowires to 750 degrees C, there was no change in the planar defects in the nanowire with respect to the as-grown nanowire; however, vanishing of the photoluminescence (PL) peak corresponding to band tail states along with enhanced band edge PL intensity, recovery of the Raman shift and increase in the Schottky barrier height from 0.1 to 0.4 eV clearly point to the efficient annihilation of point defects in these GaAsSbN nanowires. A significant reduction in the temperature induced energy shift in the annealed nanowires is attributed to annihilation of band tail states and weak temperature dependence of N-related localized states. The observation of room temperature PL signal in the 1.3 MUm region shows that the strategy of adding small amounts of N to GaAsSb is a promising route to realization of efficient nanoscale light emitters with reduced temperature sensitivity in the telecommunication wavelength region. PMID- 26831687 TI - Surfactant-Assisted Hydrothermal Synthesis of PMN-PT Nanorods. AB - The effects of surfactant polyacrylate acid (PAA) on shape evolution of 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 (0.7PMN-0.3PT) nanorods were studied. The results revealed that the polyacrylic acid content had great influence on the morphology of 0.7PMN-0.3PT. With increasing PAA concentration from 0.45 to 0.82 g/ml, the ratio of perovskite phase (PMN-PT nanorod) increased, while the ratio of pyrochlore phase decreased. When the PAA concentration was 0.82 g/ml, pure 0.7PMN 0.3PT nanorods were obtained. However, when PAA concentration was higher than 0.82 g/ml, the excess of PAA would hindered their [100] orientation growth. The piezoelectric coefficient d 33 of 0.7PMN-0.3PT nanorod was obtained by linear fitting, and the d 33 value was 409 pm/V. PMID- 26831689 TI - Formation of Surface Corrosion-Resistant Nanocrystalline Structures on Steel. AB - Engineering materials with nanocrystalline structure could be exploited under simultaneous action of mechanical loading and corrosion environments; therefore, their corrosion resistance is important. Surface nanocrystalline structure was generated on middle carbon steels by severe plastic deformation using the method of mechanical pulse friction treatment. This treatment additionally includes high temperature phase transformation and alloying. Using a complex of the corrosive, electrochemical and physical investigations, it was established that nanocrystalline structures can be characterized by lower or increased corrosion resistance in comparison with the reference material. It is caused by the action of two confronting factors: arising energy level and anticorrosive alloying of the surface layer. PMID- 26831688 TI - Single Nanoparticle Translocation Through Chemically Modified Solid Nanopore. AB - The nanopore sensor as a high-throughput and low-cost technology can detect single nanoparticle in solution. In the present study, the silicon nitride nanopores were fabricated by focused Ga ion beam (FIB), and the surface was functionalized with 3-aminopropyltriethoxysilane to change its surface charge density. The positively charged nanopore surface attracted negatively charged nanoparticles when they were in the vicinity of the nanopore. And, nanoparticle translocation speed was slowed down to obtain a clear and deterministic signal. Compared with previous studied small nanoparticles, the electrophoretic translocation of negatively charged polystyrene (PS) nanoparticles (diameter ~100 nm) was investigated in solution using the Coulter counter principle in which the time-dependent nanopore current was recorded as the nanoparticles were driven across the nanopore. A linear dependence was found between current drop and biased voltage. An exponentially decaying function (t d ~ e (-v/v0) ) was found between the duration time and biased voltage. The interaction between the amine functionalized nanopore wall and PS microspheres was discussed while translating PS microspheres. We explored also translocations of PS microspheres through amine functionalized solid-state nanopores by varying the solution pH (5.4, 7.0, and 10.0) with 0.02 M potassium chloride (KCl). Surface functionalization showed to provide a useful step to fine-tune the surface property, which can selectively transport molecules or particles. This approach is likely to be applied to gene sequencing. PMID- 26831690 TI - Improvement of Bipolar Switching Properties of Gd:SiOx RRAM Devices on Indium Tin Oxide Electrode by Low-Temperature Supercritical CO2 Treatment. AB - Bipolar switching resistance behaviors of the Gd:SiO2 resistive random access memory (RRAM) devices on indium tin oxide electrode by the low-temperature supercritical CO2-treated technology were investigated. For physical and electrical measurement results obtained, the improvement on oxygen qualities, properties of indium tin oxide electrode, and operation current of the Gd:SiO2 RRAM devices were also observed. In addition, the initial metallic filament forming model analyses and conduction transferred mechanism in switching resistance properties of the RRAM devices were verified and explained. Finally, the electrical reliability and retention properties of the Gd:SiO2 RRAM devices for low-resistance state (LRS)/high-resistance state (HRS) in different switching cycles were also measured for applications in nonvolatile random memory devices. PMID- 26831691 TI - Admittance Investigation of MIS Structures with HgTe-Based Single Quantum Wells. AB - This work presents results of the investigation of admittance of metal-insulator semiconductor structure based on Hg1 - x Cd x Te grown by molecular beam epitaxy. The structure contains a single quantum well Hg0.35Cd0.65Te/HgTe/Hg0.35Cd0.65Te with thickness of 5.6 nm in the sub-surface layer of the semiconductor. Both the conductance-voltage and capacitance-voltage characteristics show strong oscillations when the metal-insulator-semiconductor (MIS) structure with a single quantum well based on HgTe is biased into the strong inversion mode. Also, oscillations on the voltage dependencies of differential resistance of the space charge region were observed. These oscillations were related to the recharging of quantum levels in HgTe. PMID- 26831692 TI - Ultra-thin Graphitic Film: Synthesis and Physical Properties. AB - A scalable technique of chemical vapor deposition (CVD) growth of ultra-thin graphitic film is proposed. Ultra-thin graphitic films grown by a one-step CVD process on catalytic copper substrate have higher crystallinity than pyrolytic carbon grown on a non-catalytic surface and appear to be more robust than a graphene monolayer. The obtained graphitic material, not thicker than 8 nm, survives during the transfer process from a Cu substrate without a template polymer layer, typically used in the graphene transfer process to protect graphene. This makes the transfer process much more simple and cost-effective. Having electrical and optical properties compatible with what was observed for a few layers of CVD graphene, the proposed ultra-thin graphitic film offers new avenues for implementing 2D materials in real-world devices. PMID- 26831693 TI - Cross-Sectional Investigations on Epitaxial Silicon Solar Cells by Kelvin and Conducting Probe Atomic Force Microscopy: Effect of Illumination. AB - Both surface photovoltage and photocurrent enable to assess the effect of visible light illumination on the electrical behavior of a solar cell. We report on photovoltage and photocurrent measurements with nanometer scale resolution performed on the cross section of an epitaxial crystalline silicon solar cell, using respectively Kelvin probe force microscopy and conducting probe atomic force microscopy. Even though two different setups are used, the scans were performed on locations within 100-MUm distance in order to compare data from the same area and provide a consistent interpretation. In both measurements, modifications under illumination are observed in accordance with the theory of PIN junctions. Moreover, an unintentional doping during the deposition of the epitaxial silicon intrinsic layer in the solar cell is suggested from the comparison between photovoltage and photocurrent measurements. PMID- 26831694 TI - Compensating the Degradation of Near-Infrared Absorption of Black Silicon Caused by Thermal Annealing. AB - We propose the use of thin Ag film deposition to remedy the degradation of near infrared (NIR) absorption of black Si caused by high-temperature thermal annealing. A large amount of random and irregular Ag nanoparticles are formed on the microstructural surface of black Si after Ag film deposition, which compensates the degradation of NIR absorption of black Si caused by thermal annealing. The formation of Ag nanoparticles and their contributions to NIR absorption of black Si are discussed in detail. PMID- 26831695 TI - Oxidative Damage and Energy Metabolism Disorder Contribute to the Hemolytic Effect of Amorphous Silica Nanoparticles. AB - Amorphous silica nanoparticles (SiNPs) have been extensively used in biomedical applications due to their particular characteristics. The increased environmental and iatrogenic exposure of SiNPs gained great concerns on the biocompatibility and hematotoxicity of SiNPs. However, the studies on the hemolytic effects of amorphous SiNPs in human erythrocytes are still limited. In this study, amorphous SiNPs with 58 nm were selected and incubated with human erythrocytes for different times (30 min and 2 h) at various concentrations (0, 10, 20, 50, and 100 MUg/mL). SiNPs induced a dose-dependent increase in percent hemolysis and significantly increased the malondialdehyde (MDA) content and decreased the superoxide dismutase (SOD) activity, leading to oxidative damage in erythrocytes. Hydroxyl radical (.OH) levels were detected by electron spin resonance (ESR), and the decreased elimination rates of .OH showed SiNPs induced low antioxidant ability in human erythrocytes. Na(+)-K(+) ATPase activity and Ca(2+)-Mg(2+) ATPase activity were found remarkably inhibited after SiNP treatment, possibly causing energy sufficient in erythrocytes. Percent hemolysis of SiNPs was significantly decreased in the presence of N-acetyl-cysteine (NAC) and adenosine diphosphate (ADP). It was concluded that amorphous SiNPs caused dose-dependent hemolytic effects in human erythrocytes. Oxidative damage and energy metabolism disorder contributed to the hemolytic effects of SiNPs in vitro. PMID- 26831696 TI - Evaluating the Quantitative Capabilities of Metagenomic Analysis Software. AB - DNA sequencing technologies are applied widely and frequently today to describe metagenomes, i.e., microbial communities in environmental or clinical samples, without the need for culturing them. These technologies usually return short (100 300 base-pairs long) DNA reads, and these reads are processed by metagenomic analysis software that assign phylogenetic composition-information to the dataset. Here we evaluate three metagenomic analysis software (AmphoraNet--a webserver implementation of AMPHORA2--, MG-RAST, and MEGAN5) for their capabilities of assigning quantitative phylogenetic information for the data, describing the frequency of appearance of the microorganisms of the same taxa in the sample. The difficulties of the task arise from the fact that longer genomes produce more reads from the same organism than shorter genomes, and some software assign higher frequencies to species with longer genomes than to those with shorter ones. This phenomenon is called the "genome length bias." Dozens of complex artificial metagenome benchmarks can be found in the literature. Because of the complexity of those benchmarks, it is usually difficult to judge the resistance of a metagenomic software to this "genome length bias." Therefore, we have made a simple benchmark for the evaluation of the "taxon-counting" in a metagenomic sample: we have taken the same number of copies of three full bacterial genomes of different lengths, break them up randomly to short reads of average length of 150 bp, and mixed the reads, creating our simple benchmark. Because of its simplicity, the benchmark is not supposed to serve as a mock metagenome, but if a software fails on that simple task, it will surely fail on most real metagenomes. We applied three software for the benchmark. The ideal quantitative solution would assign the same proportion to the three bacterial taxa. We have found that AMPHORA2/AmphoraNet gave the most accurate results and the other two software were under-performers: they counted quite reliably each short read to their respective taxon, producing the typical genome length bias. The benchmark dataset is available at http://pitgroup.org/static/3RandomGenome 100kavg150bps.fna. PMID- 26831697 TI - Erratum to: Benchmarks for ethically credible partnerships between industry and academic health centers: beyond disclosure of financial conflicts of interest. PMID- 26831699 TI - The Assembly Line Enzymology of Polyketide Biosynthesis. AB - Polyketides are a structurally and functionally diverse family of bioactive natural products that have found widespread application as pharmaceuticals, agrochemicals, and veterinary medicines. In bacteria complex polyketides are biosynthesized by giant multifunctional megaenzymes, termed modular polyketide synthases (PKSs), which construct their products in a highly coordinated assembly line-like fashion from a pool of simple precursor substrates. Not only is the multifaceted enzymology of PKSs a fascinating target for study, but it also presents considerable opportunities for the reengineering of these systems affording access to functionally optimized unnatural natural products. Here we provide an introductory primer to modular polyketide synthase structure and function, and highlight recent advances in the characterization and exploitation of these systems. PMID- 26831698 TI - Structural Biology of Nonribosomal Peptide Synthetases. AB - The nonribosomal peptide synthetases are modular enzymes that catalyze synthesis of important peptide products from a variety of standard and non-proteinogenic amino acid substrates. Within a single module are multiple catalytic domains that are responsible for incorporation of a single residue. After the amino acid is activated and covalently attached to an integrated carrier protein domain, the substrates and intermediates are delivered to neighboring catalytic domains for peptide bond formation or, in some modules, chemical modification. In the final module, the peptide is delivered to a terminal thioesterase domain that catalyzes release of the peptide product. This multi-domain modular architecture raises questions about the structural features that enable this assembly line synthesis in an efficient manner. The structures of the core component domains have been determined and demonstrate insights into the catalytic activity. More recently, multi-domain structures have been determined and are providing clues to the features of these enzyme systems that govern the functional interaction between multiple domains. This chapter describes the structures of NRPS proteins and the strategies that are being used to assist structural studies of these dynamic proteins, including careful consideration of domain boundaries for generation of truncated proteins and the use of mechanism-based inhibitors that trap interactions between the catalytic and carrier protein domains. PMID- 26831701 TI - Affinity Purification Method for the Identification of Nonribosomal Peptide Biosynthetic Enzymes Using a Synthetic Probe for Adenylation Domains. AB - A series of inhibitors have been designed based on 5'-O-sulfamoyl adenosine (AMS) that display tight binding characteristics towards the inhibition of adenylation (A) domains in nonribosomal peptide synthetases (NRPSs). We recently developed an affinity probe for A domains that could be used to facilitate the specific isolation and identification of NRPS modules. Our synthetic probe, which is a biotinylated variant of L-Phe-AMS (L-Phe-AMS-biotin), selectively targets the A domains in NRPS modules that recognize and convert L-Phe to an aminoacyl adenylate in whole proteomes. In this chapter, we describe the design and synthesis of L-Phe-AMS-biotin and provide a summary of our work towards the development of a series of protocols for the specific enrichment of NRPS modules using this probe. PMID- 26831700 TI - Measurement of Nonribosomal Peptide Synthetase Adenylation Domain Activity Using a Continuous Hydroxylamine Release Assay. AB - Adenylation is a crucial enzymatic process in the biosynthesis of nonribosomal peptide synthetase (NRPS) derived natural products. Adenylation domains are considered the gatekeepers of NRPSs since they select, activate, and load the carboxylic acid substrate onto a downstream peptidyl carrier protein (PCP) domain of the NRPS. We describe a coupled continuous kinetic assay for NRPS adenylation domains that substitutes the PCP domain with hydroxylamine as the acceptor molecule. The pyrophosphate released from the first-half reaction is then measured using a two-enzyme coupling system, which detects conversion of the chromogenic substrate 7-methylthioguanosine (MesG) to 7-methylthioguanine. From profiling substrate specificity of unknown or engineered adenylation domains to studying chemical inhibition of adenylating enzymes, this robust assay will be of widespread utility in the broad field NRPS enzymology. PMID- 26831702 TI - Colorimetric Detection of the Adenylation Activity in Nonribosomal Peptide Synthetases. AB - Nonribosomal peptide synthetases (NRPSs) are multifunctional enzymes consisting of catalytic domains. The substrate specificities of adenylation (A) domains determine the amino-acid building blocks to be incorporated during nonribosomal peptide biosynthesis. The A-domains mediate ATP-dependent activation of amino acid substrates as aminoacyl-O-AMP with pyrophosphate (PPi) release. Traditionally, the enzymatic activity of the A-domains has been measured by radioactive ATP-[(32)P]-PPi exchange assays with the detection of (32)P-labeled ATP. Recently, we developed a colorimetric assay for the direct detection of PPi as a yellow 18-molybdopyrophosphate anion ([(P2O7)Mo18O54](4-)). [(P2O7)Mo18O54](4-) was further reduced by ascorbic acid to give a more readily distinguishable blue coloration. Here we demonstrate the lab protocols for the colorimetric assay of PPi released in A-domain reactions. PMID- 26831703 TI - Facile Synthetic Access to Glycopeptide Antibiotic Precursor Peptides for the Investigation of Cytochrome P450 Action in Glycopeptide Antibiotic Biosynthesis. AB - The glycopeptide antibiotics are an important class of complex, medically relevant peptide natural products. Given that the production of such compounds all stems from in vivo biosynthesis, understanding the mechanisms of the natural assembly system--consisting of a nonribosomal-peptide synthetase machinery (NRPS) and further modifying enzymes--is vital. In order to address the later steps of peptide biosynthesis, which are catalyzed by Cytochrome P450s that interact with the peptide-producing nonribosomal peptide synthetase, peptide substrates are required: these peptides must also be in a form that can be conjugated to carrier protein domains of the nonribosomal peptide synthetase machinery. Here, we describe a practical and effective route for the solid phase synthesis of glycopeptide antibiotic precursor peptides as their Coenzyme A (CoA) conjugates to allow enzymatic conjugation to carrier protein domains. This route utilizes Fmoc-chemistry suppressing epimerization of racemization-prone aryl glycine derivatives and affords high yields and excellent purities, requiring only a single step of simple solid phase extraction for chromatographic purification. With this, comprehensive investigations of interactions between various NRPS bound substrates and Cytochrome P450s are enabled. PMID- 26831704 TI - Reconstitution of Fungal Nonribosomal Peptide Synthetases in Yeast and In Vitro. AB - The emergence of next-generation sequencing has provided new opportunities in the discovery of new nonribosomal peptides (NRPs) and NRP synthethases (NRPSs). However, there remain challenges for the characterization of these megasynthases. While genetic methods in native hosts are critical in elucidation of the function of fungal NRPS, in vitro assays of intact heterologously expressed proteins provide deeper mechanistic insights in NRPS enzymology. Our previous work in the study of NRPS takes advantage of Saccharomyces cerevisiae strain BJ5464-npgA as a robust and versatile platform for characterization of fungal NRPSs. Here we describe the use of yeast recombination strategies in S. cerevisiae for cloning of the NRPS coding sequence in 2MU-based expression vector; the use of affinity chromatography for purification of NRPS from the total S. cerevisiae soluble protein fraction; and strategies for reconstitution of NRPSs activities in vitro. PMID- 26831705 TI - The Continuing Development of E. coli as a Heterologous Host for Complex Natural Product Biosynthesis. AB - Heterologous biosynthesis of natural products is meant to enable access to the vast array of valuable properties associated with these compounds. Often motivated by limitations inherent in native production hosts, the heterologous biosynthetic process begins with a candidate host regarded as technically advanced relative to original producing organisms. Given this requirement, E. coli has been a top choice for heterologous biosynthesis attempts as associated recombinant tools emerged and continue to develop. However, success requires overcoming challenges associated with natural product formation, including complex biosynthetic pathways and the need for metabolic support. These two challenges have been heavily featured in cellular engineering efforts completed to position E. coli as a viable surrogate host. This chapter outlines steps taken to engineer E. coli with an emphasis on genetic manipulations designed to support the heterologous production of polyketide, nonribosomal peptide, and similarly complex natural products. PMID- 26831706 TI - Screening for Expressed Nonribosomal Peptide Synthetases and Polyketide Synthases Using LC-MS/MS-Based Proteomics. AB - Liquid chromatography-mass spectrometry (LC-MS)-based proteomics is a powerful technique for the profiling of protein expression in cells in a high-throughput fashion. Herein we report a protocol using LC-MS/MS-based proteomics for the screening of enzymes involved in natural product biosynthesis, such as nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) from bacterial strains. Taking advantage of the large size of modular NRPSs and PKSs (often >200 kDa), size-based separation (SDS-PAGE) is employed prior to LC-MS/MS analysis. Based upon the protein identifications obtained through software search, we can accurately pinpoint the expressed NRPS and/or PKS gene clusters from a given strain and growth condition. The proteomics screening result can be used to guide the discovery of potentially new nonribosomal peptide and polyketide natural products. PMID- 26831708 TI - In Situ Analysis of Bacterial Lipopeptide Antibiotics by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging. AB - Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is a technique developed in the late 1990s enabling the two-dimensional mapping of a broad variety of biomolecules present at the surface of a sample. In many applications including pharmaceutical studies or biomarker discovery, the distribution of proteins, lipids or drugs, and metabolites may be visualized within tissue sections. More recently, MALDI MSI has become increasingly applied in microbiology where the versatility of the technique is perfectly suited to monitor the metabolic dynamics of bacterial colonies. The work described here is focused on the application of MALDI MSI to map secondary metabolites produced by Bacilli, especially lipopeptides, produced by bacterial cells during their interaction with their environment (bacteria, fungi, plant roots, etc.). This chapter addresses the advantages and challenges that the implementation of MALDI MSI to microbiological samples entails, including detailed protocols on sample preparation (from both microbiologist and mass spectrometrist points of view), matrix deposition, and data acquisition and interpretation. Lipopeptide images recorded from confrontation plates are also presented. PMID- 26831707 TI - Enhancing Nonribosomal Peptide Biosynthesis in Filamentous Fungi. AB - Filamentous fungi are historically known as rich sources for production of biologically active natural products, so-called secondary metabolites. One particularly pharmaceutically relevant chemical group of secondary metabolites is the nonribosomal peptides synthesized by nonribosomal peptide synthetases (NRPSs). As most of the fungal NRPS gene clusters leading to production of the desired molecules are not expressed under laboratory conditions, efforts to overcome this impediment are crucial to unlock the full chemical potential of each fungal species. One way to activate these silent clusters is by overexpressing and deleting global regulators of secondary metabolism. The conserved fungal-specific regulator of secondary metabolism, LaeA, was shown to be a valuable target for sleuthing of novel gene clusters and metabolites. Additionally, modulation of chromatin structures by either chemical or genetic manipulation has been shown to activate cryptic metabolites. Furthermore, NRPS derived molecules seem to be affected by cross talk between the specific gene clusters and some of these metabolites have a tissue- or developmental-specific regulation. This chapter summarizes how this knowledge of different tiers of regulation can be combined to increase production of NRPS-derived metabolites in fungal species. PMID- 26831709 TI - Secondary Metabolic Pathway-Targeted Metabolomics. AB - This chapter provides step-by-step methods for building secondary metabolic pathway-targeted molecular networks to assess microbial natural product biosynthesis at a systems level and to aid in downstream natural product discovery efforts. Methods described include high-resolution mass spectrometry (HRMS)-based comparative metabolomics, pathway-targeted tandem MS (MS/MS) molecular networking, and isotopic labeling for the elucidation of natural products encoded by orphan biosynthetic pathways. The metabolomics network workflow covers the following six points: (1) method development, (2) bacterial culture growth and organic extraction, (3) HRMS data acquisition and analysis, (4) pathway-targeted MS/MS data acquisition, (5) mass spectral network building, and (6) network enhancement. This chapter opens with a discussion on the practical considerations of natural product extraction, chromatographic processing, and enhanced detection of the analytes of interest within complex organic mixtures using liquid chromatography (LC)-HRMS. Next, we discuss the utilization of a chemometric platform, focusing on Agilent Mass Profiler Professional software, to run MS-based differential analysis between sample groups and controls to acquire a unique set of molecular features that are dependent on the presence of a secondary metabolic pathway. Using this unique list of molecular features, the chapter then details targeted MS/MS acquisition for subsequent pathway-dependent network clustering through the online Global Natural Products Social Molecular Networking (GnPS) platform. Genetic information, ionization intensities, isotopic labeling, and additional experimental data can be mapped onto the pathway-dependent network, facilitating systems biosynthesis analyses. The finished product will provide a working molecular network to assess experimental perturbations and guide novel natural product discoveries. PMID- 26831710 TI - Annotating and Interpreting Linear and Cyclic Peptide Tandem Mass Spectra. AB - Nonribosomal peptides often possess pronounced bioactivity, and thus, they are often interesting hit compounds in natural product-based drug discovery programs. Their mass spectrometric characterization is difficult due to the predominant occurrence of non-proteinogenic monomers and, especially in the case of cyclic peptides, the complex fragmentation patterns observed. This makes nonribosomal peptide tandem mass spectra annotation challenging and time-consuming. To meet this challenge, software tools for this task have been developed. In this chapter, the workflow for using the software mMass for the annotation of experimentally obtained peptide tandem mass spectra is described. mMass is freely available (http://www.mmass.org), open-source, and the most advanced and user friendly software tool for this purpose. The software enables the analyst to concisely annotate and interpret tandem mass spectra of linear and cyclic peptides. Thus, it is highly useful for accelerating the structure confirmation and elucidation of cyclic as well as linear peptides and depsipeptides. PMID- 26831711 TI - Bioinformatics Tools for the Discovery of New Nonribosomal Peptides. AB - This chapter helps in the use of bioinformatics tools relevant to the discovery of new nonribosomal peptides (NRPs) produced by microorganisms. The strategy described can be applied to draft or fully assembled genome sequences. It relies on the identification of the synthetase genes and the deciphering of the domain architecture of the nonribosomal peptide synthetases (NRPSs). In the next step, candidate peptides synthesized by these NRPSs are predicted in silico, considering the specificity of incorporated monomers together with their isomery. To assess their novelty, the two-dimensional structure of the peptides can be compared with the structural patterns of all known NRPs. The presented workflow leads to an efficient and rapid screening of genomic data generated by high throughput technologies. The exploration of such sequenced genomes may lead to the discovery of new drugs (i.e., antibiotics against multi-resistant pathogens or anti-tumors). PMID- 26831712 TI - The Use of ClusterMine360 for the Analysis of Polyketide and Nonribosomal Peptide Biosynthetic Pathways. AB - Polyketides and nonribosomal peptides constitute two large families of microbial natural products. Over the past 20 years a broad range of microbial polyketide and nonribosomal peptide biosynthetic pathways have been characterized leading to a surfeit of genetic data on polyketide and nonribosomal peptide biosynthesis. We developed the ClusterMine360 database, which stores the antiSMASH-based annotation of gene clusters in the NCBI database, linking the structure of the natural product to the biosynthetic gene cluster. This database is searchable and enables the user to access multiple sequence files for phylogenetic analysis of polyketide and nonribosomal peptide biosynthetic genes. Herein we describe how to add compound families and gene clusters to the database and search it using key words or structures to identify specific gene clusters. We also describe how to download multiple sequence files for specific catalytic domains from polyketide and nonribosomal peptide biosynthesis. PMID- 26831713 TI - Alignment-Free Methods for the Detection and Specificity Prediction of Adenylation Domains. AB - Identifying adenylation domains (A-domains) and their substrate specificity can aid the detection of nonribosomal peptide synthetases (NRPS) at genome/proteome level and allow inferring the structure of oligopeptides with relevant biological activities. However, that is challenging task due to the high sequence diversity of A-domains (~10-40 % of amino acid identity) and their selectivity for 50 different natural/unnatural amino acids. Altogether these characteristics make their detection and the prediction of their substrate specificity a real challenge when using traditional sequence alignment methods, e.g., BLAST searches. In this chapter we describe two workflows based on alignment-free methods intended for the identification and substrate specificity prediction of A domains. To identify A-domains we introduce a graphical-numerical method, implemented in TI2BioP version 2.0 (topological indices to biopolymers), which in a first step uses protein four-color maps to represent A-domains. In a second step, simple topological indices (TIs), called spectral moments, are derived from the graphical representations of known A-domains (positive dataset) and of unrelated but well-characterized sequences (negative set). Spectral moments are then used as input predictors for statistical classification techniques to build alignment-free models. Finally, the resulting alignment-free models can be used to explore entire proteomes for unannotated A-domains. In addition, this graphical-numerical methodology works as a sequence-search method that can be ensemble with homology-based tools to deeply explore the A-domain signature and cope with the diversity of this class (Aguero-Chapin et al., PLoS One 8(7):e65926, 2013). The second workflow for the prediction of A-domain's substrate specificity is based on alignment-free models constructed by transductive support vector machines (TSVMs) that incorporate information of uncharacterized A-domains. The construction of the models was implemented in the NRPSpredictor and in a first step uses the physicochemical fingerprint of the 34 residues lining the active site of the phenylalanine-adenylation domain of gramicidin synthetase A [PDB ID 1 amu] to derive a feature vector. Homologous positions were extracted for A-domains with known and unknown substrate specificities and turned into feature vectors. At the same time, A-domains with known specificities towards similar substrates were clustered by physicochemical properties of amino acids (AA). In a second step, support vector machines (SVMs) were optimized from feature vectors of characterized A-domains in each of the resulting clusters. Later, SVMs were used in the variant of TSVMs that integrate a fraction of uncharacterized A-domains during training to predict unknown specificities. Finally, uncharacterized A-domains were scored by each of the constructed alignment-free models (TSVM) representing each substrate specificity resulting from the clustering. The model producing the largest score for the uncharacterized A-domain assigns the substrate specificity to it (Rausch et al., Nucleic Acids Res 33:5799-5808, 2005). PMID- 26831714 TI - Characterization of Nonribosomal Peptide Synthetases with NRPSsp. AB - Bioinformatic sequence analysis allows the functional characterization of newly sequenced proteins. Nonribosomal peptide synthetases (NRPSs) are multi-modular enzymes involved in the biosynthesis of natural products. The current omics era has enabled the exponential growth of the sequenced NRPS, and it is important to characterize the final product of these synthetases. Here, how to achieve the prediction of substrates which bind to adenylation domains in NRPS with NRPSsp (www.nrpssp.com) bioinformatic tool is described. PMID- 26831715 TI - Phase I Dose-Escalation Study of Linsitinib (OSI-906) and Erlotinib in Patients with Advanced Solid Tumors. AB - PURPOSE: Cross-talk between type I IGF receptor (IGF1R), insulin receptor (INSR), and epidermal growth factor receptor (EGFR) mediates resistance to individual receptor blockade. This study aimed to determine the MTD, safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of linsitinib, a potent oral IGF1R/INSR inhibitor, with EGFR inhibitor erlotinib. EXPERIMENTAL DESIGN: This open-label, dose-escalation study investigated linsitinib schedules S1: once daily intermittent (days 1-3 weekly); S2, once daily continuous; S3, twice-daily continuous; each with erlotinib 100-150 mg once daily; and a non-small cell lung cancer (NSCLC) expansion cohort. RESULTS: Ninety five patients were enrolled (S1, 44; S2, 24; S3, 12; expansion cohort, 15) and 91 treated. Seven experienced dose-limiting toxicities: QTc prolongation (3), abnormal liver function (2), hyperglycemia (1), and anorexia (1). Common adverse events included drug eruption (84%), diarrhea (73%), fatigue (68%), nausea (58%), vomiting (40%). MTDs for linsitinib/erlotinib were 450/150 mg (S1), 400/100 mg (S2). On the basis of prior monotherapy data, S3 dosing at 150 mg twice daily/150 mg once daily was the recommended phase II dose for the expansion cohort. There was no evidence of drug-drug interaction. Pharmacodynamic data showed IGF-1 elevation and reduced IGF1R/INSR phosphorylation, suggesting pathway inhibition. Across schedules, 5/75 (7%) evaluable patients experienced partial responses: spinal chordoma (268+ weeks), rectal cancer (36 weeks), three NSCLCs including 2 adenocarcinomas (16, 72 weeks), 1 squamous wild-type EGFR NSCLC (36 weeks). Disease control (CR+PR+SD) occurred in 38 of 75 (51%), and 28 of 91 (31%) patients were on study >12 weeks. CONCLUSIONS: The linsitinib/erlotinib combination was tolerable with preliminary evidence of activity, including durable responses in cases unlikely to respond to erlotinib monotherapy. Clin Cancer Res; 22(12); 2897-907. (c)2016 AACR. PMID- 26831716 TI - Androgen Deprivation Followed by Acute Androgen Stimulation Selectively Sensitizes AR-Positive Prostate Cancer Cells to Ionizing Radiation. AB - PURPOSE: The current standard of care for patients with locally advanced prostate cancer is a combination of androgen deprivation and radiation therapy. Radiation is typically given with androgen suppression when testosterone levels are at their nadir. Recent reports have shown that androgen stimulation of androgen deprived prostate cancer cells leads to formation of double-strand breaks (DSB). Here, we exploit this finding and investigate the extent and timing of androgen induced DSBs and their effect on tumor growth following androgen stimulation in combination with ionizing radiation (IR). EXPERIMENTAL DESIGN: Androgen-induced DNA damage was assessed by comet assays and gammaH2A.X foci formation. Effects of androgen stimulation and radiation were determined in vitro and in vivo with xenograft models. RESULTS: We document that androgen treatment of androgen deprived prostate cancer cell lines resulted in a dose- and time-dependent induction of widespread DSBs. Generation of these breaks was dependent on androgen receptor and topoisomerase II beta but not on cell-cycle progression. In vitro models demonstrated a synergistic interaction between IR and androgen stimulation when IR is given at a time point corresponding with high levels of androgen-induced DSB formation. Furthermore, in vivo studies showed a significant improvement in tumor growth delay when radiation was given shortly after androgen repletion in castrated mice. CONCLUSIONS: These results suggest a potential cooperative effect and improved tumor growth delay with androgen-induced DSBs and radiation with implications for improving the therapeutic index of prostate cancer radiation therapy. Clin Cancer Res; 22(13); 3310-9. (c)2016 AACRSee related commentary by Chua and Bristow, p. 3124. PMID- 26831717 TI - Mutations in TSC1, TSC2, and MTOR Are Associated with Response to Rapalogs in Patients with Metastatic Renal Cell Carcinoma. AB - PURPOSE: We examined the hypothesis that mutations in mTOR pathway genes are associated with response to rapalogs in metastatic renal cell carcinoma (mRCC). EXPERIMENTAL DESIGN: We studied a cohort of mRCC patients who were treated with mTOR inhibitors with distinct clinical outcomes. Tumor DNA from 79 subjects was successfully analyzed for mutations using targeted next-generation sequencing of 560 cancer genes. Responders were defined as those with partial response (PR) by RECIST v1.0 or stable disease with any tumor shrinkage for 6 months or longer. Nonresponders were defined as those with disease progression during the first 3 months of therapy. Fisher exact test assessed the association between mutation status in mTOR pathway genes and treatment response. RESULTS: Mutations in MTOR, TSC1, or TSC2 were more common in responders, 12 (28%) of 43, than nonresponders, 4 (11%) of 36 (P = 0.06). Mutations in TSC1 or TSC2 alone were also more common in responders, 9 (21%), than nonresponders, 2(6%), (P = 0.05). Furthermore, 5 (42%) of 12 subjects with PR had mutations in MTOR, TSC1, or TSC2 compared with 4 (11%) of 36 nonresponders (P = 0.03). Eight additional non-mTOR pathway genes were found to be mutated in at least 4 of 79 tumors (5%); none were associated positively with response. CONCLUSIONS: In this cohort of mRCC patients, mutations in MTOR, TSC1, or TSC2 were more common in patients who experienced clinical benefit from rapalogs than in those who progressed. However, a substantial fraction of responders (24 of 43, 56%) had no mTOR pathway mutation identified. Clin Cancer Res; 22(10); 2445-52. (c)2016 AACRSee related commentary by Voss and Hsieh, p. 2320. PMID- 26831718 TI - IgG Glycome in Colorectal Cancer. AB - PURPOSE: Alternative glycosylation has significant structural and functional consequences on IgG and consequently also on cancer immunosurveillance. Because of technological limitations, the effects of highly heritable individual variations and the differences in the dynamics of changes in IgG glycosylation on colorectal cancer were never investigated before. EXPERIMENTAL DESIGN: Using recently developed high-throughput UPLC technology for IgG glycosylation analysis, we analyzed IgG glycome composition in 760 patients with colorectal cancer and 538 matching controls. Effects of surgery were evaluated in 28 patients sampled before and three times after surgery. A predictive model was built using regularized logistic regression and evaluated using a 10-cross validation procedure. Furthermore, IgG glycome composition was analyzed in 39 plasma samples collected before initial diagnosis of colorectal cancer. RESULTS: We have found that colorectal cancer associates with decrease in IgG galactosylation, IgG sialylation and increase in core-fucosylation of neutral glycans with concurrent decrease of core-fucosylation of sialylated glycans. Although a model based on age and sex did not show discriminative power (AUC = 0.499), the addition of glycan variables into the model considerably increased the discriminative power of the model (AUC = 0.755). However, none of these differences were significant in the small set of samples collected before the initial diagnosis. CONCLUSIONS: Considering the functional relevance of IgG glycosylation for both tumor immunosurveillance and clinical efficacy of therapy with mAbs, individual variation in IgG glycosylation may turn out to be important for prediction of disease course or the choice of therapy, thus warranting further, more detailed studies of IgG glycosylation in colorectal cancer. Clin Cancer Res; 22(12); 3078-86. (c)2016 AACR. PMID- 26831719 TI - Micrometastasis Volume in Lymph Nodes Determines Disease Recurrence Rate of Stage II Colorectal Cancer: A Prospective Multicenter Trial. AB - PURPOSE: We reported in a retrospective study that the presence of micrometastasis in lymph nodes, when assessed by carcinoembryonic antigen (CEA) specific RT-PCR, is a significant prognostic factor in stage II colorectal cancer. The aim of this study was to clarify the clinical value of micrometastasis in a prospective multicenter trial. EXPERIMENTAL DESIGN: From November 2001 to December 2005, a total of 419 colorectal cancer cases were preoperatively registered at a central data center. Of them, 315 node-negative stage II colorectal cancer cases were enrolled. After RNA quality check, 304 colorectal cancer cases were analyzed for CEA mRNA in lymph nodes by both conventional RT-PCR (a band method) and quantitative RT-PCR. Long-term prognosis of the patients was determined by each method. RESULTS: A positive band for CEA mRNA was detected in 73 (24.0%) of 304 patients. Postoperative adjuvant chemotherapy was applied in 31 CEA band-positive cases with an oral 5 fluorouracil derivative HCFU (1-hexylcarbamoyl-5-fluorouracil) for 1 year, whereas chemotherapy was not administered to CEA band-negative group. Multivariate Cox regression analyses revealed that a high micrometastasis volume (high MMV, n = 95) was an independent poor prognostic factor for 5-year disease free survival (DFS; P = 0.001) and 5-year overall survival (OS; P = 0.016). CONCLUSIONS: This prospective clinical trial demonstrates that micrometastasis volume is a useful marker in identifying patients who are at high or low risk for recurrence of stage II colorectal cancer. Clin Cancer Res; 22(13); 3201-8. (c)2016 AACR. PMID- 26831720 TI - How do we improve men's mental health via primary care? An evaluation of the Atlas Men's Well-being Pilot Programme for stressed/distressed men. AB - BACKGROUND: Over three-quarters of all suicides are men (England and Wales), this is despite higher levels of anxiety and depression being reported by women. This disparity may in part be explained by atypical presentations of distress in men, and gendered issues around help-seeking. Consequently, the Atlas Men's Well-being Programme was designed to engage stressed/distressed men who were patients at a London-based GP surgery. Atlas encouraged GPs to identify and refer men for counselling and/or acupuncture by raising their awareness of men's distress. The aim of this pilot study was to evaluate Atlas in terms of patients' characteristics, service utilisation, patient outcomes and cost implications. METHODS: All patients using the Programme were asked to complete a questionnaire before and after their Atlas sessions. Outcome measures included the Hospital Anxiety and Depression scale, Perceived Stress Scale, Warwick-Edinburgh Mental Well-being Scale, a 11-point scale measuring physical health, and the Psychological Outcome Profiles (PSYCHLOPS), a patient-generated outcome measure. Additionally, for cost calculations, participants were asked about their employment, number of days off work due to illness, and their health and social care service use. RESULTS: 102 participants were recruited, 82 completed pre- and post-treatment questionnaires. Comparisons pre- and post-treatment revealed a statistically significant improvement in anxious mood (p <0.001), perceived stress (p < 0.001), positive well-being (p = <0.001), PSYCHLOPS (p = <0.001) and physical health (p = 0.001), though not depressed mood (p = 0.660). Additionally, reductions in costs related to lost employment and health and social care use, exceeded the cost of Atlas counselling and acupuncture sessions, with an average saving of nearly L700 per patient. CONCLUSIONS: Atlas attendance was associated with improvements in patients' mental and physical health, and demonstrated likely cost savings. It is now important to understand patient and stakeholder perspectives. Further research could compare usual care with the Atlas approach, and investigate full cost-effectiveness. PMID- 26831721 TI - Increase in non-tuberculous mycobacteria isolated from humans in Tuscany, Italy, from 2004 to 2014. AB - BACKGROUND: In Italy, the prevalence of non-tuberculous mycobacteria (NTM) in human infections is largely unknown. Herein, we report the epidemiology of NTM infections in a region of central Italy, Tuscany, over the last 11 years, and provide a review of the recent literature on NTM isolation rates in different geographic regions. METHODS: The complete collection of NTM strains isolated from a total of 42,055 clinical specimens at the Laboratory of Clinical Mycobacteriology of Pisa University Hospital, Italy, from 1 January 2004 to 31 December 2014 was included. RESULTS: In our setting, in the period 2004-2014 a total of 147 patients had cultures positive for NTM. The number of NTM isolates increased considerably from five isolates in 2004 to 29 in 2014; a sharp increase occurred in the last 3 years. Overall, 16 NTM species were isolated; the most common were M. avium, M. intracellulare and M. gordonae detected in respectively in 41.5, 14.3 and 11.6% of NTM patients. In general, NTM isolates were largely prevalent in people older than 60 (57.8%); patients aged 1-10 year-old almost exclusively yielded M. avium and M. intracellulare. Of the 147 NTM clinical isolates, 76.2% were from respiratory specimens, 10.9% from lymph nodes, 2.7% from blood (yielding exclusively M. avium), and the remaining 10.2% from other clinical specimens. CONCLUSIONS: The observed increase in NTM isolation rate in our setting is in keeping with the general increase in NTM infections reported worldwide in the past two decades, although the distribution of the NTM prevalent species differs by geographic region. PMID- 26831722 TI - Evaluating the interstitial lung disease multidisciplinary meeting: a survey of expert centres. AB - BACKGROUND: Multidisciplinary meetings (MDM) are the current "gold standard" in interstitial lung disease (ILD) diagnosis and comprise inter-disciplinary discussion of multiple forms of information to provide diagnostic and management outputs. Although bias could be potentially inserted at any step in the discussion process, to date there has been no consensus regarding the appropriate constitution and governance of MDM. We sought to determine the features of ILD MDMs based within ILD centres of excellence around the world. METHODS: An internet based questionnaire was sent to twelve expert centres in Europe, North America, and Australia seeking information regarding the structure and governance of their MDM. Data was analysed for consistent themes and points of contrast. RESULTS: Responses were received from 10 out of 12 centres. Similarities were demonstrated with regards to contributing attendees, meeting frequency and case numbers reviewed. Significant heterogeneity in attendee speciality group type, quantity and method of data presentation, approach to diagnosis formulation and documentation, and information provision was apparent. CONCLUSIONS: The constitution of ILD MDMs differs considerably between expert centres. Such differences may result in discordant outcomes, and emphasise the need for further evidence regarding the appropriate constitution and governance of ILD MDMs. PMID- 26831723 TI - Severity of burn and its related factors: A study from the developing country Pakistan. AB - BACKGROUND: Burns are leading cause of fatal injuries and major cause of morbidity and mortality in developing countries. The major obstacle in controlling severity is factors related to burn. This study determines frequency of burns and the factors related to it in Karachi, Pakistan. METHODS: A cross sectional study was conducted and 384 hospitalized adult patients with burns were consecutively interviewed during August 2013 to February 2014. Information was collected on socio-demographic profile, intent of burn, severity of burn, health hazards, physical and psychological characteristics. TBSA burn of >15% was considered as higher severity of burn. RESULTS: Higher severity of burns was found in 76.3% patients. Multivariate analysis showed that higher severity of burns were significantly associated with age less than 25 years (OR 2.7, 95% CI 1.5-4.9), never had been to school (OR 3.1, 95% CI 1.7-5.9) and intentional burn (OR 20.6, 95% CI 5.0-84.9). CONCLUSION: Majority of patients had higher severity of burn. The intent of injury was intentional, age less than 25 years and no schooling were found significantly associated with higher severity of burns. PMID- 26831724 TI - Maternal dietary intake and physical activity habits during the postpartum period: associations with clinician advice in a sample of Australian first time mothers. AB - BACKGROUND: Numerous health benefits are associated with achieving optimal diet and physical activity behaviours during and after pregnancy. Understanding predictors of these behaviours is an important public health consideration, yet little is known regarding associations between clinician advice and diet and physical activity behaviours in postpartum women. The aims of this study were to compare the frequency of dietary and physical activity advice provided by clinicians during and after pregnancy and assess if this advice is associated with postpartum diet and physical activity behaviours. METHODS: First time mothers (n = 448) enrolled in the Melbourne InFANT Extend trial completed the Cancer Council of Australia's Food Frequency Questionnaire when they were three to four months postpartum, which assessed usual fruit and vegetable intake (serves/day). Total physical activity time, time spent walking and time in both moderate and vigorous activity for the previous week (min/week) were assessed using the Active Australia Survey. Advice received during and following pregnancy were assessed by separate survey items, which asked whether a healthcare practitioner had discussed eating a healthy diet and being physically active. Linear and logistic regression assessed associations of advice with dietary intake and physical activity. RESULTS: In total, 8.6% of women met guidelines for combined fruit and vegetable intake. Overall, mean total physical activity time was 350.9 +/- 281.1 min/week. Time spent walking (251.97 +/- 196.78 min/week), was greater than time spent in moderate (36.68 +/- 88.58 min/week) or vigorous activity (61.74 +/- 109.96 min/week) and 63.2% of women were meeting physical activity recommendations. The majority of women reported they received advice regarding healthy eating (87.1%) and physical activity (82.8%) during pregnancy. Fewer women reported receiving healthy eating (47.5%) and physical activity (51.9%) advice by three months postpartum. There was no significant association found between provision of dietary and/or physical activity advice, and mother's dietary intakes or physical activity levels. CONCLUSIONS: Healthy diet and physical activity advice was received less after pregnancy than during pregnancy yet no association between receipt of advice and behaviour was observed. More intensive approaches than provision of advice may be required to promote healthy diet and physical activity behaviours in new mothers. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12611000386932 13/04/2011). PMID- 26831725 TI - Local anesthetic injections with or without steroid for chronic non-cancer pain: a protocol for a systematic review and meta-analysis of randomized controlled trials. AB - BACKGROUND: Steroids are often combined with local anesthetic (LA) and injected to reduce pain associated with various chronic non-cancer pain (CNCP) complaints. The biological rationale behind injection of a steroid solution is unclear, and it is uncertain whether the addition of steroids offers any additional benefits over injection of LA alone. We propose to conduct a systematic review and meta analysis to summarize the evidence for using steroids and LA vs. LA alone in the treatment of CNCP. METHODS: An experienced librarian will perform a comprehensive search of EMBASE, MEDLINE, and the Cochrane Central Registry of Controlled Trials (CENTRAL) databases with search terms for clinical indications, LA, and steroid agents. We will review bibliographies of all relevant published reviews in the last 5 years for additional studies. Eligible trials will be published in English and randomly allocate patients with CNCP to treatment with steroid and LA injection therapy or injection with LA alone. We will use the guidelines published by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to inform the outcomes that we collect and present. Teams of reviewers will independently and in duplicate assess trial eligibility, abstract data, and assess risk of bias among eligible trials. We will prioritize intention to treat analysis and, when possible, pool outcomes across trials using random effects models. We will report our findings as risk differences, weighted mean differences, or standardized mean differences for individual outcomes. Further, to ensure interpretability of our results, we will present risk differences and measures of relative effect for pain reduction based on anchor based minimally important clinical differences. We will conduct a priori defined subgroup analyses and use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to evaluate the certainty of the evidence on an outcome-by-outcome basis. DISCUSSION: Our review will evaluate both the effectiveness and the adverse events associated with steroid plus LA vs. LA alone for CNCP, evaluate the quality of the evidence using the GRADE approach, and prioritize patient-important outcomes guided by IMMPACT recommendations. Our results will facilitate evidence-based management of patients with chronic non cancer pain and identify key areas for future research. TRIAL REGISTRATION: PROSPERO CRD42015020614. PMID- 26831730 TI - Magnetic Resonance Imaging of Perirenal Pathology. AB - The perirenal space can be involved by a variety of neoplastic, inflammatory, infectious, and proliferative disorders. Magnetic resonance imaging is often an ideal technique for identification and staging of lesions arising within the perirenal space, with its superior soft tissue characterization as well as its ability to visualize extension into blood vessels and adjacent organs. This pictorial essay describes the magnetic resonance imaging appearance of a variety of pathologies which can arise from or involve the perirenal space, and provides a framework for categorization and differential diagnosis of these lesions. PMID- 26831729 TI - Convergent evolution of hemoglobin switching in jawed and jawless vertebrates. AB - BACKGROUND: During development, humans and other jawed vertebrates (Gnathostomata) express distinct hemoglobin genes, resulting in different hemoglobin tetramers. Embryonic and fetal hemoglobin have higher oxygen affinities than the adult hemoglobin, sustaining the oxygen demand of the developing organism. Little is known about the expression of hemoglobins during development of jawless vertebrates (Agnatha). RESULTS: We identified three hemoglobin switches in the life cycle of the sea lamprey. Three hemoglobin genes are specifically expressed in the embryo, four genes in the filter feeding larva (ammocoete), and nine genes correspond to the adult hemoglobin chains. During the development from the parasitic to the reproductive adult, the composition of hemoglobin changes again, with a massive increase of chain aHb1. A single hemoglobin chain is expressed constitutively in all stages. We further showed the differential expression of other globin genes: Myoglobin 1 is most highly expressed in the reproductive adult, myoglobin 2 expression peaks in the larva. Globin X1 is restricted to the embryo; globin X2 was only found in the reproductive adult. Cytoglobin is expressed at low levels throughout the life cycle. CONCLUSION: Because the hemoglobins of jawed and jawless vertebrates evolved independently from a common globin ancestor, hemoglobin switching must also have evolved convergently in these taxa. Notably, the ontogeny of sea lamprey hemoglobins essentially recapitulates their phylogeny, with the embryonic hemoglobins emerging first, followed by the evolution of larval and adult hemoglobins. PMID- 26831727 TI - Caries remineralisation and arresting effect in children by professionally applied fluoride treatment - a systematic review. AB - BACKGROUND: As a low-cost and easily operated treatment, the use of professionally applied topical fluoride was approved for preventing dental caries and remineralising early enamel caries or white spot lesions. It is also used to arrest dentine caries. The aim of this study is to investigate the clinical efficacy of professional fluoride therapy in remineralising and arresting caries in children. METHOD: A systematic search of publications from 1948 to 2014 was conducted using four databases: PubMed, Cochrane Library, ISI Web of Science and Embase. The key words used were (fluoride) AND (remineralisation OR remineralization OR arresting) AND (children caries OR early childhood caries). The title and abstract of initially identified publications were screened. Clinical trials about home-use fluorides, laboratory studies, case reports, reviews, non-English articles and irrelevant studies were excluded. The full texts of the remaining papers were retrieved. Manual screening was conducted on the bibliographies of the remaining papers to identify relevant articles. RESULTS: A total of 2177 papers were found, and 17 randomised clinical trials were included in this review. Ten studies investigated the remineralising effect on early enamel caries using silicon tetrafluoride, fluoride gel, silver diamine fluoride or sodium fluoride. Seven studies reported an arresting effect on dentine caries using silver diamine fluoride or nano-silver fluoride. Meta analysis was performed on four papers using 5 % sodium fluoride varnish to remineralise early enamel caries, and the overall percentage of remineralised enamel caries was 63.6 % (95 % CI: 36.0 % - 91.2 %; p < 0.001). Meta-analysis was also performed on five papers using 38 % silver diamine fluoride to arrest dentine caries and the overall proportion of arrested dentine caries was 65.9 % (95 % CI: 41.2 % - 90.7 %; p < 0.001). CONCLUSION: Professionally applied 5 % sodium fluoride varnish can remineralise early enamel caries and 38 % silver diamine fluoride is effective in arresting dentine caries. PMID- 26831726 TI - A new in vitro mouse oligodendrocyte precursor cell migration assay reveals a role for integrin-linked kinase in cell motility. AB - BACKGROUND: The decline of remyelination in chronic multiple sclerosis (MS) is in part attributed to inadequate oligodendrocyte precursor cell (OPC) migration, a process governed by the extracellular matrix (ECM). Elucidating the mechanisms underlying OPC migration is therefore an important step towards developing new therapeutic strategies to promote myelin repair. Many seminal OPC culture methods were established using rat-sourced cells, and these often need modification for use with mouse OPCs due to their sensitive nature. It is of interest to develop mouse OPC assays to leverage the abundant transgenic lines. To this end, we developed a new OPC migration method specifically suited for use with mouse derived cells. RESULTS: To validate its utility, we combined the new OPC migration assay with a conditional knockout approach to investigate the role of integrin-linked kinase (ILK) in OPC migration. ILK is a focal adhesion protein that stabilizes cellular adhesions to the extracellular matrix (ECM) by mediating a linkage between matrix-bound integrin receptors and the cytoskeleton. We identified ILK as a regulator of OPC migration on three permissive substrates. ILK loss produced an early, albeit transient, deficit in OPC migration on laminin matrix, while migration on fibronectin and polylysine was heavily reliant on ILK expression. CONCLUSIONS: Inclusively, our work provides a new tool for studying mouse OPC migration and highlights the role of ILK in its regulation on ECM proteins relevant to MS. PMID- 26831731 TI - An Audit of Pain Experienced During Image-Guided Breast Biopsy Procedures at an Academic Center. PMID- 26831732 TI - Diagnostic Performance of Combined Contrast-Enhanced Magnetic Resonance Angiography and Phase-Contrast Magnetic Resonance Imaging in Suspected Subclavian Steal Syndrome. AB - PURPOSE: The study sought to evaluate the efficacy of magnetic resonance imaging (MRI) in patients with suspected subclavian steal syndrome (SSS) using both contrast-enhanced (CE) MR angiography and phase-contrast (PC) MRI. METHODS: Fifteen suspected SSSs from 13 patients were evaluated using CE-MR angiography and PC-MRI. Ten patients also received dynamic CE-MR angiography. RESULTS: All MRI examinations were technically successful. By combining CE-MR angiography with PC-MRI, 10 SSSs were diagnosed in 9 patients. The delay enhancement dynamic technique predicted SSS with a sensitivity, specificity, and accuracy of 57.1%, 100%, and 72.7%, respectively. Without the dynamic technique, affected delay enhanced arteries were poorly visualized and could be mistaken for occluded vessels. Retrograde vertebral flow by PC-MRI was used to predict ipsilateral SSS with a sensitivity, specificity, and accuracy of 100%, 60%, and 86.7%, respectively. There were 2 false positives including 1 patient with a proximal total occlusion of the affected vertebral artery and another with brachiocephalic steal syndrome rather than SSS. This suggested that retrograde vertebral flow does not always indicate SSS. CONCLUSIONS: CE-MR angiography combined with PC-MRI is efficacious when evaluating SSS in clinical practice. PMID- 26831733 TI - How Competitive Is the Canadian Diagnostic Radiology Residency Match? Application and Matching Trends From 1991-2014. AB - PURPOSE: The study sought to evaluate application trends in Canadian diagnostic radiology residency programs and to assess the relative competitiveness of radiology as a specialty. METHODS: The Canadian Residency Matching Service Reports from 1991-2014 for Canadian graduates were used to extract the total residency positions and radiology residency positions, number of applicants to all specialties and to radiology, number of first-choice radiology applicants, number of unmatched radiology positions, and number of positions and applicants to each specialty. Ratios were calculated: radiology positions to applicants and first-choice applicants, first-choice radiology applicants to applicants for all specialties, and training positions to applicants in each specialty. Data trends and correlation coefficients were analysed. RESULTS: The number of radiology residency positions offered increased, with strong positive correlation (r = 0.91, P < .001), while the number of applicants increased with only a moderate positive correlation (r = 0.49, P = .03). Radiology was the most competitive in 1997, with a ratio of 0.32 positions/applicant. There was an increase of positions/applicant over time (decreasing competitiveness; r = 0.76, P < .001) but no change in positions/first-choice applicant (r = 0.11, P = .65). The highest percentage of applicants who ranked radiology as their first choice was in 2003 at 6.5% with a decrease in this percentage over time (r = -0.36, P = .13). Radiology is moderately competitive for positions/overall applicants and very competitive for positions/first-choice applicants compared to other specialties. CONCLUSIONS: The number of radiology residency positions has increased while the number of applicants has not grown commensurately. The match was most competitive in 1997, and decreased in subsequent years. Possible reasons include job market, reimbursement, and work environment. PMID- 26831734 TI - Transcranial Direct Current Stimulation (tDCS) Enhances the Excitability of Trigemino-Facial Reflex Circuits. AB - BACKGROUND: Transcranial direct current stimulation (tDCS) causes a tiny burning sensation through activation of local cutaneous trigeminal afferents. HYPOTHESIS: Trigeminal sensory inputs from tDCS may generate excitability changes in the trigemino-facial reflex circuits. OBJECTIVES AND METHODS: Sixteen healthy volunteers were submitted to 20 minutes tDCS sessions with two types of electrode montage conditions: 1. Real vs Sham 'bi-hemispheric' tDCS (cathode/anode: C4/C3), for blinded assessment of effects, and 2. 'uni-hemispheric' tDCS (cathode/anode: Fp3/C3), for assessment of laterality of the effects. Supraorbital nerve stimuli were used to obtain blink reflexes before, during (10 minutes from onset) and after (30 minutes from onset) the tDCS session. Outcome measures were R2 habituation (R2H) to repeated stimuli, the blink reflex excitability recovery (BRER) to paired stimuli and the blink reflex inhibition by a prepulse (BRIP). RESULTS: Real but not sham bi-hemispheric tDCS caused a significant decrease of R2H and leftward shift of BRER curve (p < 0.05 for all measures). The effects of uni-hemispheric tDCS on BRER and BRIP were larger on ipsilateral than on contralateral blink reflexes (p < 0.05). Excitability changes were still present 10 minutes after the end of stimulation in a lesser extent. CONCLUSIONS: This study shows that 20 minute tDCS enhances the excitability of trigemino-facial reflex circuits. The finding of larger ipsilateral than contralateral effects suggests that sensitization through cutaneous trigeminal afferents adds on other possible mechanisms such as activation of cortico-nuclear or cortico-reticular connections. PMID- 26831735 TI - Secretion of IL-1beta from imatinib-resistant chronic myeloid leukemia cells contributes to BCR-ABL mutation-independent imatinib resistance. AB - Some cases of chronic myelogenous leukemia are resistant to tyrosine kinase inhibitors (TKIs) independently of mutation in BCR-ABL, but the detailed mechanism underlying this resistance has not yet been elucidated. In this study, we generated a TKI-resistant CML cell line, K562R, that lacks a mutation in BCR ABL. Interleukin-1beta (IL-1beta) was more highly expressed in K562R than in the parental cell line K562S, and higher levels of IL-1beta contributed to the imatinib resistance of K562R. In addition, IL-1beta secreted from K562R cells affected stromal cell production of CXCL11, which in turn promoted migration of K562R cells into the stroma. Thus, elevated IL-1beta production from TKI resistant K562R cells may contribute to TKI resistance by increasing cell viability and promoting cell migration. PMID- 26831736 TI - GPs in UK follow lung cancer guidelines less closely than in other countries, study finds. PMID- 26831737 TI - Microbiome: Transgenerational missing taxa. PMID- 26831738 TI - Coagulansin-A has beneficial effects on the development of bovine embryos in vitro via HSP70 induction. AB - Coagulansin-A (withanolide) is the steroidal lactone obtained from Withania coagulans which belong to Solanaceae family. The present study investigated the effects of coagulansin-A on bovine oocyte maturation and embryo development in vitro. All these oocytes were aspirated from the ovaries obtained from Korean Hanwoo cows at a local abattoir. To determine whether coagulansin-A has beneficial effects on bovine oocyte maturation in vitro, 355 oocytes per group (control and treated) in seven replicates were subjected with different concentrations (1, 2.5, 5, 7.5 and 10 MUM) of coagulansin-A. The coagulansin-A was added in the in vitro maturation (IVM) media followed by in vitro fertilization (IVF) and then in vitro culture (IVC). Only treatment with 5 MUM coagulansin-A remarkably (P<0.05) improved embryos development (Day 8 blastocyst) having 27.30 and 40.01% for control and coagulansin-A treated groups respectively. Treatment with 5 MUM coagulansin-A significantly induced activation of heat shock protein 70 (HSP70) (P<0.05). Immunofluorescence analysis revealed that 5 MUM coagulansin-A treatment also significantly inhibited oxidative stress and inflammation during bovine embryo development in vitro by decreasing 8 oxoguanosine (8-OxoG) (P<0.05) and nuclear factor-kappaB (NF-kappaB) (P<0.05). The expressions of HSP70 and NF-kappaB were also conformed through real-time PCR (RT-PCR). Additionally, the terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay confirmed that coagulansin-A treatment significantly improved the embryo quality and reduced bovine embryo DNA damage (P<0.05). The present study provides new information regarding the mechanisms by which coagulansin-A promotes bovine embryo development in vitro. PMID- 26831739 TI - [What and how to evaluate clinical-surgical competence. The resident and staff surgeon perspective]. AB - BACKGROUND: Evaluation is a means for significant and rigorous improvement of the educational process. Therefore, competence evaluation should allow assessing the complex activity of medical care, as well as improving the training process. This is the case in the evaluation process of clinical-surgical competences. MATERIALS AND METHODS: A cross-sectional study was designed to measure knowledge about the evaluation of clinical-surgical competences for the General Surgery residency program at the Faculty of Medicine, Universidad Autonoma de Chihuahua (UACH). A 55-item questionnaire divided into six sections was used (perception, planning, practice, function, instruments and strategies, and overall evaluation), with a six level Likert scale, performing a descriptive, correlation and comparative analysis, with a significance level of 0.001. RESULTS: In both groups perception of evaluation was considered as a further qualification. As regards tools, the best known was the written examination. As regards function, evaluation was considered as a further administrative requirement. In the correlation analysis, evaluation was perceived as qualification and was significantly associated with measurement, assessment and accreditation. In the comparative analysis between residents and staff surgeons, a significant difference was found as regards the perception of the evaluation as a measurement of knowledge (Student t test: p=0.04). CONCLUSION: The results provide information about the concept we have about the evaluation of clinical-surgical competences, considering it as a measure of learning achievement for a socially required certification. There is confusion as regards the perception of evaluation, its function, goals and scopes as benefit for those evaluated. PMID- 26831740 TI - Mobile Telephone Text Messaging for Medication Adherence in Chronic Disease: A Meta-analysis. AB - IMPORTANCE: Adherence to long-term therapies in chronic disease is poor. Traditional interventions to improve adherence are complex and not widely effective. Mobile telephone text messaging may be a scalable means to support medication adherence. OBJECTIVES: To conduct a meta-analysis of randomized clinical trials to assess the effect of mobile telephone text messaging on medication adherence in chronic disease. DATA SOURCES: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, and CINAHL (from database inception to January 15, 2015), as well as reference lists of the articles identified. The data were analyzed in March 2015. STUDY SELECTION: Randomized clinical trials evaluating a mobile telephone text message intervention to promote medication adherence in adults with chronic disease. DATA EXTRACTION: Two authors independently extracted information on study characteristics, text message characteristics, and outcome measures as per the predefined protocol. MAIN OUTCOMES AND MEASURES: Odds ratios and pooled data were calculated using random-effects models. Risk of bias and study quality were assessed as per Cochrane guidelines. Disagreement was resolved by consensus. RESULTS: Sixteen randomized clinical trials were included, with 5 of 16 using personalization, 8 of 16 using 2-way communication, and 8 of 16 using a daily text message frequency. The median intervention duration was 12 weeks, and self-report was the most commonly used method to assess medication adherence. In the pooled analysis of 2742 patients (median age, 39 years and 50.3% [1380 of 2742] female), text messaging significantly improved medication adherence (odds ratio, 2.11; 95% CI, 1.52-2.93; P < .001). The effect was not sensitive to study characteristics (intervention duration or type of disease) or text message characteristics (personalization, 2-way communication, or daily text message frequency). In a sensitivity analysis, our findings remained robust to change in inclusion criteria based on study quality (odds ratio, 1.67; 95% CI, 1.21-2.29; P = .002). There was moderate heterogeneity (I2 = 62%) across clinical trials. After adjustment for publication bias, the point estimate was reduced but remained positive for an intervention effect (odds ratio, 1.68; 95% CI, 1.18-2.39). CONCLUSIONS AND RELEVANCE: Mobile phone text messaging approximately doubles the odds of medication adherence. This increase translates into adherence rates improving from 50% (assuming this baseline rate in patients with chronic disease) to 67.8%, or an absolute increase of 17.8%. While promising, these results should be interpreted with caution given the short duration of trials and reliance on self-reported medication adherence measures. Future studies need to determine the features of text message interventions that improve success, as well as appropriate patient populations, sustained effects, and influences on clinical outcomes. PMID- 26831742 TI - The EU Clinical Trials Regulation: key priorities, purposes and aims and the implications for public health. AB - The replacement of the European Union (EU) Clinical Trials Directive by the new Clinical Trials Regulation (CTR), which entered into force on 16 June 2014 but will not apply before 28 May 2016, provides an opportunity to review the legal and political context within which this important aspect of research law and policy sits and to reflect on the implications for public health. My aim in this article is to relate the context to the key purposes and aims of EU law and policy on clinical trials in order to explain and clarify its orientation. On that basis, I argue that the CTR and the changes it introduces to the law on clinical trials are part of the EU's continued focus on market optimisation. It is this focus that orients and directs the wider pharmaceutical development pipeline, but that undermines the achievement of key public health objectives. PMID- 26831741 TI - Deletion of the hemopexin or heme oxygenase-2 gene aggravates brain injury following stroma-free hemoglobin-induced intracerebral hemorrhage. AB - BACKGROUND: Following intracerebral hemorrhage (ICH), red blood cells release massive amounts of toxic heme that causes local brain injury. Hemopexin (Hpx) has the highest binding affinity to heme and participates in its transport, while heme oxygenase 2 (HO2) is the rate-limiting enzyme for the degradation of heme. Microglia are the resident macrophages in the brain; however, the significance and role of HO2 and Hpx on microglial clearance of the toxic heme (iron protoporphyrin IX) after ICH still remain understudied. Accordingly, we postulated that global deletion of constitutive HO2 or Hpx would lead to worsening of ICH outcomes. METHODS: Intracerebral injection of stroma-free hemoglobin (SFHb) was used in our study to induce ICH. Hpx knockout (Hpx(-/-)) or HO2 knockout (HO2(-/-)) mice were injected with 10 MUL of SFHb in the striatum. After injection, behavioral/functional tests were performed, along with anatomical analyses. Iron deposition and neuronal degeneration were depicted by Perls' and Fluoro-Jade B staining, respectively. Immunohistochemistry with anti ionized calcium-binding adapter protein 1 (Iba1) was used to estimate activated microglial cells around the injured site. RESULTS: This study shows that deleting Hpx or HO2 aggravated SFHb-induced brain injury. Compared to wild-type littermates, larger lesion volumes were observed in Hpx(-/-) and HO2(-/-) mice, which also bear more degenerating neurons in the peri-lesion area 24 h postinjection. Fewer Iba1-positive microglial cells were detected at the peri lesion area in Hpx(-/-) and HO2(-/-) mice, interestingly, which is associated with markedly increased iron-positive microglial cells. Moreover, the Iba1 positive microglial cells increased from 24 to 72 h postinjection and were accompanied with improved neurologic deficits in Hpx(-/-) and HO2(-/-) mice. These results suggest that Iba1-positive microglial cells could engulf the extracellular SFHb and provide protective effects after ICH. We then treated cultured primary microglial cells with SFHb at low and high concentrations. The results show that microglial cells actively take up the extracellular SFHb. Of interest, we also found that iron overload in microglia significantly reduces the Iba1 expression level and resultantly inhibits microglial phagocytosis. CONCLUSIONS: This study suggests that microglial cells contribute to hemoglobin heme clearance after ICH; however, the resultant iron overloads in microglia appear to decrease Iba1 expression and to further inhibit microglial phagocytosis. PMID- 26831743 TI - Clinical Course among Cases of Acute Liver Failure of Indeterminate Diagnosis. AB - OBJECTIVE: To investigate the heterogeneity in clinical course among those with pediatric acute liver failure (PALF) of indeterminate disease etiology. STUDY DESIGN: We studied participants enrolled in the PALF registry study with indeterminate final diagnosis. Growth mixture modeling was used to analyze participants' international normalized ratio, total bilirubin, and hepatic encephalopathy trajectories in the first 7 days following enrollment. Participants with at least 3 values for 1 or more of the measurements were included. We examined the association between the resulting latent subgroup classification with participants' characteristics and disease outcomes. Data from participants with PALF of specified etiologies were used to investigate the potential diagnostic value of the latent subgroups. RESULTS: In this sample of 380 participants with indeterminate final diagnosis, 115 (30%) experienced mild and quickly improving disease trajectories and another 48 (13%) started with severe disease but improved by day 7. The majority of participants (216, 57%) had disease trajectories that worsened over time. The identified patterns of disease trajectories are predictive of outcome (P < .001). The trajectory patterns are associated with the underlying disease etiology (P < .001) for the 488 participants with PALF of specified etiologies. CONCLUSIONS: The clinical courses of participants with PALF of indeterminate disease etiology exhibit distinct trajectory patterns, which have important prognostic and potentially diagnostic value. PMID- 26831745 TI - Effective Radiation Dose in a Skeletal Survey Performed for Suspected Child Abuse. AB - Effective dose of a skeletal survey in infants using digital radiography was estimated to be 0.2 mSv using Monte Carlo simulation. Radiation risk from this procedure is, therefore, low. Radiation concern should not be an overriding factor when deciding whether skeletal survey is needed in cases of possible physical abuse. PMID- 26831746 TI - The Human Alzheimer Disease Project: Answering the Call. PMID- 26831744 TI - Kidney Disease Progression in Autosomal Recessive Polycystic Kidney Disease. AB - OBJECTIVE: To define glomerular filtration rate (GFR) decline, hypertension (HTN), and proteinuria in subjects with autosomal recessive polycystic kidney disease (ARPKD) and compare with 2 congenital kidney disease control groups in the Chronic Kidney Disease in Children cohort. STUDY DESIGN: GFR decline (iohexol clearance), rates of HTN (ambulatory/casual blood pressures), antihypertensive medication usage, left ventricular hypertrophy, and proteinuria were analyzed in subjects with ARPKD (n = 22) and 2 control groups: aplastic/hypoplastic/dysplastic disorders (n = 44) and obstructive uropathies (n = 44). Differences between study groups were examined with the Wilcoxon rank sum test. RESULTS: Annualized GFR change in subjects with ARPKD was -1.4 mL/min/1.73 m(2) (-6%), with greater decline in subjects age >= 10 years (-11.5%). However, overall rates of GFR decline did not differ significantly in subjects with ARPKD vs controls. There were no significant differences in rates of HTN or left ventricular hypertrophy, but subjects with ARPKD had a greater percent on >= 3 blood pressure medications (32% vs 0%, P < .0001), more angiotensin-converting enzyme inhibitor use (82% vs 27% vs 36%, P < .0005), and less proteinuria (urine protein: creatinine = 0.1 vs 0.6, P < .005). CONCLUSIONS: This study reports rates of GFR decline, HTN, and proteinuria in a small but well-phenotyped ARPKD cohort. The relatively slow rate of GFR decline in subjects with ARPKD and absence of significant proteinuria suggest that these standard clinical measures may have limited utility in assessing therapeutic interventions and highlight the need for other ARPKD kidney disease progression biomarkers. PMID- 26831748 TI - [The fate of the oral communications presented at the SIFUD congress (2006 2012)]. AB - INTRODUCTION: The subjects presented at scientific congresses often remain confidential because of the non-indexation of the communications. A subsequent publication is necessary for the dissemination of knowledge. The value of a congress is somehow rated by the level of its publications. OBJECTIVES: To analyze, quantitatively and qualitatively, the fate of the communications presented orally at the annual meeting of the SIFUD-PP between 2006 and 2012. METHOD: From the authors' names and the title of the communications presented orally at congresses between 2006 and 2012, we investigated if those communications had resulted as an indexed publication PubMed/Medline until April 2015. We studied anonymously the correlation between the data presented in the communication provided at the SIFUD-PP congress and the data published in the final article. We evaluated the "value" of the publication according to the language of publication (French/English), the ranking of the magazine (A or B versus others), and the number of citations of the article in Google-Scholar. RESULTS: A total of 270 oral communications were presented at the SIFUD congress between 2006 and 2012, so an average of 38.5 (+/-15) per year. Globally, 110 articles (40%) have been published in an indexed journal PubMed/MedLine to date (April 2015). Note that 10 articles of the oral communications (8%) were published before the congress. The average time of publication was 22 months+/-15 months. In terms of the language of publication, 79 articles (71%) were published in English magazines. They were published in 31 different journals (49 articles [44%] in urology, 14 articles [12%] in gynecology, 12 articles [10%] in urogynecology, 11 articles [10%] in coloproctology, 16 articles [14%] in neuro urology and physical medicine and rehabilitation, 3 articles [2%] in sexology). Sixty-three articles (57%) were published in journals with an impact factor (IF) higher than 2 and 39 articles (35%) were published in journals of rank A or B. DISCUSSION: The rate of publications of oral communications varies according to specialties and the type of the congress. For example, the rate of the published communications at the ICS Congress (International Continence Society) in 2003 was 61% and of the AFU (French Association of Urology) in 2000, was 34.5%. The rate of publication of the oral abstracts presented at the SIFUD (40% over the period 2006-2012) is comparable to other national congresses but slightly inferior to those of international congresses. Several hypotheses may explain the non publication of the oral communications (quitting the project, communication about preliminary results, refused publication by many journals) and unfortunately we do not have those results. We should get back individually to the submitters to know the reasons for non-publication of their works. CONCLUSION: In the end, 40% of the oral communication presented at the annual congress of the SIFUD were published in an indexed journals PubMed/MedLine. Seventy-one percent of them are in English. LEVEL OF EVIDENCE: 4. PMID- 26831749 TI - Successful treatment of young infants presenting neonatal diabetes mellitus with continuous subcutaneous insulin infusion before genetic diagnosis. AB - AIMS: Neonatal diabetes mellitus (NDM) is defined as hyperglycemia and impaired insulin secretion with onset within 6 months of birth. While rare, NDM presents complex challenges regarding the management of glycemic control. The availability of continuous subcutaneous insulin infusion pumps (CSII) in combination with continuous glucose monitoring systems (CGM) provides an opportunity to monitor glucose levels more closely and deliver insulin more safely. METHODS: We report four cases of young infants with NDM successfully treated with CSII and CGM. Moreover, in two cases with Kir 6.2 mutation, we describe the use of CSII in switching therapy from insulin to sulfonylurea treatment. RESULTS: Insulin pump requirement for the 4 neonatal diabetes cases was the same regardless of disease pathogenesis and c-peptide levels. No dilution of insulin was needed. The use of an integrated CGM system helped in a more precise control of BG levels with the possibility of several modifications of insulin basal rates. Moreover, as showed in the first two case-reports, when the treatment was switched from insulin to glibenclamide, according to identification of Kir 6.2 mutation and diagnosis of NPDM, the CSII therapy demonstrated to be helpful in allowing gradual insulin suspension and progressive introduction of sulfonylurea. CONCLUSIONS: During the neonatal period, the use of CSII therapy is safe, more physiological, accurate and easier for the insulin administration management. Furthermore, CSII therapy is safe during the switch of therapy from insulin to glibenclamide for infants with permanent neonatal diabetes mellitus. PMID- 26831747 TI - C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation. AB - Complement C1q is the activator of the classical pathway. However, it is now recognized that C1q can exert functions unrelated to complement activation. Here we show that C1q, but not C4, is expressed in the stroma and vascular endothelium of several human malignant tumours. Compared with wild-type (WT) or C3- or C5 deficient mice, C1q-deficient (C1qa(-/-)) mice bearing a syngeneic B16 melanoma exhibit a slower tumour growth and prolonged survival. This effect is not attributable to differences in the tumour-infiltrating immune cells. Tumours developing in WT mice display early deposition of C1q, higher vascular density and an increase in the number of lung metastases compared with C1qa(-/-) mice. Bone marrow (BM) chimeras between C1qa(-/-) and WT mice identify non-BM-derived cells as the main local source of C1q that can promote cancer cell adhesion, migration and proliferation. Together these findings support a role for locally synthesized C1q in promoting tumour growth. PMID- 26831752 TI - Ion therapy for uveal melanoma in new human eye phantom based on GEANT4 toolkit. AB - Radiotherapy with ion beams like proton and carbon has been used for treatment of eye uveal melanoma for many years. In this research, we have developed a new phantom of human eye for Monte Carlo simulation of tumors treatment to use in GEANT4 toolkit. Total depth-dose profiles for the proton, alpha, and carbon incident beams with the same ranges have been calculated in the phantom. Moreover, the deposited energy of the secondary particles for each of the primary beams is calculated. The dose curves are compared for 47.8MeV proton, 190.1MeV alpha, and 1060MeV carbon ions that have the same range in the target region reaching to the center of tumor. The passively scattered spread-out Bragg peak (SOBP) for each incident beam as well as the flux curves of the secondary particles including neutron, gamma, and positron has been calculated and compared for the primary beams. The high sharpness of carbon beam's Bragg peak with low lateral broadening is the benefit of this beam in hadrontherapy but it has disadvantages of dose leakage in the tail after its Bragg peak and high intensity of neutron production. However, proton beam, which has a good conformation with tumor shape owing to the beam broadening caused by scattering, can be a good choice for the large-size tumors. PMID- 26831751 TI - Utilizing Remote Real-Time Videoconferencing to Expand Access to Cancer Genetic Services in Community Practices: A Multicenter Feasibility Study. AB - BACKGROUND: Videoconferencing has been used to expand medical services to low access populations and could increase access to genetic services at community sites where in-person visits with genetic providers are not available. OBJECTIVE: To evaluate the feasibility of, patient feedback of, and cognitive and affective responses to remote two-way videoconferencing (RVC) telegenetic services at multiple sociodemographically diverse community practices without access to genetic providers. METHODS: Patients at 3 community sites in 2 US states outside the host center completed RVC pretest (visit 1, V1) and post-test (visit 2, V2) genetic counseling for cancer susceptibility. Surveys evaluated patient experiences, knowledge, satisfaction with telegenetic and cancer genetics services, anxiety, depression, and cancer worry. RESULTS: A total of 82 out of 100 (82.0%) approached patients consented to RVC services. A total of 61 out of 82 patients (74%) completed pretest counseling and 41 out of 61 (67%) proceeded with testing and post-test counseling. A total of 4 out of 41 (10%) mutation carriers were identified: BRCA2, MSH2, and PMS2. Patients reported many advantages (eg, lower travel burden and convenience) and few disadvantages to RVC telegenetic services. Most patients reported feeling comfortable with the video camera--post-V1: 52/57 (91%); post-V2: 39/41 (95%)--and that their privacy was respected--post-V1: 56/57 (98%); post-V2: 40/41 (98%); however, some reported concerns that RVC might increase the risk of a confidentiality breach of their health information--post-V1: 14/57 (25%); post-V2: 12/41 (29%). While the majority of patients reported having no trouble seeing or hearing the genetic counselor--post-V1: 47/57 (82%); post-V2: 39/41 (95%)--51 out of 98 (52%) patients reported technical difficulties. Nonetheless, all patients reported being satisfied with genetic services. Compared to baseline, knowledge increased significantly after pretest counseling (+1.11 mean score, P=.005); satisfaction with telegenetic (+1.74 mean score, P=.02) and genetic services (+2.22 mean score, P=.001) increased after post-test counseling. General anxiety and depression decreased after pretest (-0.97 mean anxiety score, P=.003; -0.37 mean depression score, P=.046) and post-test counseling (-1.13 mean anxiety score, P=.003; -0.75 mean depression score, P=.01); state anxiety and cancer-specific worry did not significantly increase. CONCLUSIONS: Remote videoconferencing telegenetic services are feasible, identify genetic carriers in community practices, and are associated with high patient satisfaction and favorable cognitive and affective outcomes, suggesting an innovative delivery model for further study to improve access to genetic providers and services. Potential barriers to dissemination include technology costs, unclear billing and reimbursement, and state requirements for provider licensure. PMID- 26831753 TI - Dosimetric evaluation of 4 different treatment modalities for curative-intent stereotactic body radiation therapy for isolated thoracic spinal metastases. AB - To investigate the dosimetric characteristics of 4 SBRT-capable dose delivery systems, CyberKnife (CK), Helical TomoTherapy (HT), Volumetric Modulated Arc Therapy (VMAT) by Varian RapidArc (RA), and segmental step-and-shoot intensity modulated radiation therapy (IMRT) by Elekta, on isolated thoracic spinal lesions. CK, HT, RA, and IMRT planning were performed simultaneously for 10 randomly selected patients with 6 body types and 6 body + pedicle types with isolated thoracic lesions. The prescription was set with curative intent and dose of either 33Gy in 3 fractions (3F) or 40Gy in 5F to cover at least 90% of the planning target volume (PTV), correspondingly. Different dosimetric indices, beam on time, and monitor units (MUs) were evaluated to compare the advantages/disadvantages of each delivery modality. In ensuring the dose-volume constraints for cord and esophagus of the premise, CK, HT, and RA all achieved a sharp conformity index (CI) and a small penumbra volume compared to IMRT. RA achieved a CI comparable to those from CK, HT, and IMRT. CK had a heterogeneous dose distribution in the target as its radiosurgical nature with less dose uniformity inside the target. CK had the longest beam-on time and the largest MUs, followed by HT and RA. IMRT presented the shortest beam-on time and the least MUs delivery. For the body-type lesions, CK, HT, and RA satisfied the target coverage criterion in 6 cases, but the criterion was satisfied in only 3 (50%) cases with the IMRT technique. For the body + pedicle-type lesions, HT satisfied the criterion of the target coverage of >=90% in 4 of the 6 cases, and reached a target coverage of 89.0% in another case. However, the criterion of the target coverage of >=90% was reached in 2 cases by CK and RA, and only in 1 case by IMRT. For curative-intent SBRT of isolated thoracic spinal lesions, RA is the first choice for the body-type lesions owing to its delivery efficiency (time); the second choice is CK or HT; HT is the preferential choice for the body + pedicle-type lesions. This study suggests further clinical investigations with longer follow-up for these studied cases. PMID- 26831754 TI - Allele-specific DNA hypomethylation characterises FSHD1 and FSHD2. AB - BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is associated with an epigenetic defect on 4qter. Two clinically indistinguishable forms of FSHD are known, FSHD1 and FSHD2. FSHD1 is caused by contraction of the highly polymorphic D4Z4 macrosatellite repeat array on chromosome 4q35. FSHD2 is caused by pathogenic mutations of the SMCHD1 gene.Both genetic defects lead to D4Z4 DNA hypomethylation. In the presence of a polymorphic polyadenylation signal (PAS), DNA hypomethylation leads to inappropriate expression of the D4Z4-encoded DUX4 transcription factor in skeletal muscle. Currently, hypomethylation is not diagnostic per se because of the interference of non-pathogenic arrays and the lack of information about the presence of DUX4-PAS. METHODS: We investigated, by bisulfite sequencing, the DNA methylation levels of the region distal to the D4Z4 array selectively in PAS-positive alleles. RESULTS: Comparison of FSHD1, FSHD2 and Control subjects showed a highly significant difference of methylation levels in all CpGs tested. Importantly, using a cohort of 112 samples, one of these CpGs (CpG6) is able to discriminate the affected individuals with a sensitivity of 0.95 supporting this assay potential for FSHD diagnosis. Moreover, our study showed a relationship between PAS-specific methylation and severity of the disease. CONCLUSIONS: These data point to the CpGs distal to the D4Z4 array as a critical region reflecting multiple factors affecting the epigenetics of FSHD. Additionally, methylation analysis of this region allows the establishment of a rapid and sensitive tool for FSHD diagnosis. PMID- 26831755 TI - A study of common Mendelian disease carriers across ageing British cohorts: meta analyses reveal heterozygosity for alpha 1-antitrypsin deficiency increases respiratory capacity and height. AB - BACKGROUND: Several recessive Mendelian disorders are common in Europeans, including cystic fibrosis (CFTR), medium-chain-acyl-Co-A-dehydrogenase deficiency (ACADM), phenylketonuria (PAH) and alpha 1-antitrypsin deficiency (SERPINA1). METHODS: In a multicohort study of >19,000 older individuals, we investigated the relevant phenotypes in heterozygotes for these genes: lung function (forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC)) for CFTR and SERPINA1; cognitive measures for ACADM and PAH; and physical capability for ACADM, PAH and SERPINA1. RESULTS: Findings were mostly negative but lung function in SERPINA1 (protease inhibitor (PI) Z allele, rs28929474) showed enhanced FEV1 and FVC (0.13 z-score increase in FEV1 (p=1.7 * 10(-5)) and 0.16 z-score increase in FVC (p=5.2 * 10(-8))) in PI-MZ individuals. Height adjustment (a known, strong correlate of FEV1 and FVC) revealed strong positive height associations of the Z allele (1.50 cm increase in height (p=3.6 * 10(-10))). CONCLUSIONS: The PI-MZ rare (2%) SNP effect is nearly four times greater than the 'top' common height SNP in HMGA2. However, height only partially attenuates the SERPINA1-FEV1 or FVC association (around 50%) and vice versa. Height SNP variants have recently been shown to be positively selected collectively in North versus South Europeans, while the Z allele high frequency is localised to North Europe. Although PI-ZZ is clinically disadvantageous to lung function, PI-MZ increases both height and respiratory function; potentially a balanced polymorphism. Partial blockade of PI could conceivably form part of a future poly-therapeutic approach in very short children. The notion that elastase inhibition should benefit patients with chronic obstructive pulmonary disease may also merit re-evaluation. PI is already a therapeutic target: our findings invite a reconsideration of the optimum level in respiratory care and novel pathway potential for development of agents for the management of growth disorders. PMID- 26831756 TI - HSP110 T17 simplifies and improves the microsatellite instability testing in patients with colorectal cancer. AB - BACKGROUND: Every colorectal cancer (CRC) patient should be tested for microsatellite instability (MSI, a marker for defective DNA mismatch repair) as a first screen for Lynch syndrome (LS). In this study, we investigated whether it may be possible to improve the detection of MSI in CRC. We examined whether the HT17 DNA repeat (critical for correct splicing of the chaperone HSP110) might constitute a superior marker for diagnosis of the MSI phenotype in patients with CRC compared with the standard panel of markers (pentaplex). METHODS: The HT17 polymorphism was analysed in germline DNA from 1037 multi-ethnic individuals. We assessed its sensitivity and specificity for detecting MSI in a multicentre, population-based cohort of 685 patients with CRC and an additional series of 70 patients with CRC considered to be at-risk of LS. All cases were screened earlier for MSI using pentaplex markers. Cases showing discordant HT17/pentaplex results were further examined for the expression of mismatch repair proteins. RESULTS: HT17 status was analysed independently and blinded to previous results from pentaplex genotyping. HT17 showed no germline allelic variation outside a very narrow range. Compared with the pentaplex panel, HT17 showed better sensitivity (0.984 (95% CI 0.968 to 0.995) vs 0.951 (95% CI 0.925 to 0.972)) and similar specificity (0.997 (95% CI 0.989 to 1.000) for both) for the detection of MSI. Furthermore, HT17 alone correctly classified samples judged to be uncertain with the pentaplex panel and showed excellent ability to detect MSI in patients with LS. CONCLUSIONS: HT17 simplifies and improves the current standard molecular methods for detecting MSI in CRC. PMID- 26831757 TI - Sequential domain assembly of ribosomal protein S3 drives 40S subunit maturation. AB - Eukaryotic ribosomes assemble by association of ribosomal RNA with ribosomal proteins into nuclear precursor particles, which undergo a complex maturation pathway coordinated by non-ribosomal assembly factors. Here, we provide functional insights into how successive structural re-arrangements in ribosomal protein S3 promote maturation of the 40S ribosomal subunit. We show that S3 dimerizes and is imported into the nucleus with its N-domain in a rotated conformation and associated with the chaperone Yar1. Initial assembly of S3 with 40S precursors occurs via its C-domain, while the N-domain protrudes from the 40S surface. Yar1 is replaced by the assembly factor Ltv1, thereby fixing the S3 N domain in the rotated orientation and preventing its 40S association. Finally, Ltv1 release, triggered by phosphorylation, and flipping of the S3 N-domain into its final position results in the stable integration of S3. Such a stepwise assembly may represent a new paradigm for the incorporation of ribosomal proteins. PMID- 26831758 TI - Levels and potential health risk of heavy metals in marketed vegetables in Zhejiang, China. AB - The present study analyzed 5785 vegetables for concentrations of As, Cd, Cr, Pb, Ni and Hg, and estimated the health risk to local consumers by deterministic (point estimates) approaches. Levels of elements varied in different vegetables. Average levels of As, Cd, Cr, Ni, Hg and Pb were 0.013, 0.017, 0.057, 0.002, 0.094 and 0.034 mg/kg (fresh weight), respectively. The samples with 0.25% for Cd and 1.56% for Pb were exceeding the maximum allowable concentrations (MACs) set by the Chinese Health Ministry. No obvious regular geographical distribution for these metals in vegetables was found in areas of Zhejiang, China. The mean and 97.5 percentile levels of heavy metal and metalloid were used to present the mean and high exposure assessment. The health indices (HIs) were less than the threshold of 1 both in mean and high exposure assessment. It indicates that for the general people there is very low health risk to As, Cd, Cr, Pb, Ni and Hg by vegetable intake. PMID- 26831759 TI - Preparation of Aluminum Nanomesh Thin Films from an Anodic Aluminum Oxide Template as Transparent Conductive Electrodes. AB - We have employed anodic aluminum oxide as a template to prepare ultrathin, transparent, and conducting Al films with a unique nanomesh structure for transparent conductive electrodes. The anodic aluminum oxide template is obtained through direct anodization of a sputtered Al layer on a glass substrate, and subsequent wet etching creates the nanomesh metallic film. The optical and conductive properties are greatly influenced by experimental conditions. By tuning the anodizing time, transparent electrodes with appropriate optical transmittance and sheet resistance have been obtained. The results demonstrate that our proposed strategy can serve as a potential method to fabricate low-cost TCEs to replace conventional indium tin oxide materials. PMID- 26831760 TI - [Not Available]. PMID- 26831761 TI - How can next-generation diagnostics aid pancreatic adenocarcinoma treatment? PMID- 26831762 TI - Monitoring Nanoscale Deformations in a Drawn Polymer Melt with Single-Molecule Fluorescence Polarization Microscopy. AB - Elongating a polymer melt causes polymer segments to align and polymer coils to deform along the drawing direction. Despite the importance of this molecular response for understanding the viscoelastic properties and relaxation behavior of polymeric materials, studies on the single-molecule level are rare and were not performed in real time. Here we use single-molecule fluorescence polarization microscopy for monitoring the position and orientation of single fluorescent perylene diimide molecules embedded in a free-standing thin film of a polymethyl acrylate (PMA) melt with a time resolution of 500 ms during the film drawing and the subsequent stress relaxation period. The orientation distribution of the perylene diimide molecules is quantitatively described with a model of rod-like objects embedded in a uniaxially elongated matrix. The orientation of the fluorescent probe molecules is directly coupled to the local deformation of the PMA melt, which we derive from the distances between individual dye molecules. In turn, the fluorescence polarization monitors the shape deformation of the polymer coils on a length scale of 5 nm. During stress relaxation, the coil shape relaxes four times more slowly than the mechanical stress. This shows that stress relaxation involves processes on length scales smaller than a polymer coil. Our work demonstrates how optical spectroscopy and microscopy can be used to study the coupling of individual fluorescent probe molecules to their embedding polymeric matrix and to an external mechanical stimulus on the single-molecule level. PMID- 26831764 TI - Selective Template Wetting Routes to Hierarchical Polymer Films: Polymer Nanotubes from Phase-Separated Films via Solvent Annealing. AB - We demonstrate a novel wetting method to prepare hierarchical polymer films with polymer nanotubes on selective regions. This strategy is based on the selective wetting abilities of polymer chains, annealed in different solvent vapors, into the nanopores of porous templates. Phase-separated films of polystyrene (PS) and poly(methyl methacrylate) (PMMA), two commonly used polymers, are prepared as a model system. After anodic aluminum oxide (AAO) templates are placed on the films, the samples are annealed in vapors of acetic acid, in which the PMMA chains are swollen and wet the nanopores of the AAO templates selectively. As a result, hierarchical polymer films containing PMMA nanotubes can be obtained after the AAO templates are removed. The distribution of the PMMA nanotubes of the hierarchical polymer films can also be controlled by changing the compositions of the polymer blends. This work not only presents a novel method to fabricate hierarchical polymer films with polymer nanotubes on selective regions, but also gives a deeper understanding in the selective wetting ability of polymer chains in solvent vapors. PMID- 26831763 TI - Neonatal imitation and early social experience predict gaze following abilities in infant monkeys. AB - Individuals vary in their social skills and motivation, the causes of which remain largely unknown. Here we investigated whether an individual's propensity to interact with others measured within days after birth, and differences in infants' early social environment, may predict a later social skill. Specifically, we tested whether neonatal imitation--newborns' capacity to match modelled actions--and social experience in the first months of life predict gaze following (directing attention to locations where others look), in infant macaques (Macaca mulatta; n = 119). Facial gesture imitation in the first week of life predicted gaze following at 7 months of age. Imitators were better at gaze following than non-imitators, suggesting neonatal imitation may be an early marker predicting socio-cognitive functioning. In addition, infants with rich social environments outperformed infants with less socialization, suggesting early social experiences also support the development of infants' gaze following competence. The present study offers compelling evidence that an individual difference present from birth predicts a functional social cognitive skill in later infancy. In addition, this foundational skill--gaze following--is plastic, and can be improved through social interactions, providing infants with a strong foundation for later social interaction and learning. PMID- 26831766 TI - Depth perception in autostereograms: 1/f noise is best. AB - An autostereogram is a single image that encodes depth information that pops out when looking at it. The trick is achieved by setting a basic 2D pattern and continuously replicating the local pattern at each point in the image with a shift defined by the desired disparity. In this work, we explore the dependency between the ease of perceiving depth in autostereograms and the choice of the basic pattern used for generating them. We report the results of three sets of psychophysical experiments using autostereograms generated from 2D random noise patterns having power spectra of the form 1/f(beta) The experiments were designed to test the ability of human subjects to identify smooth low-resolution surfaces, as well as detail, in the form of higher-resolution objects in the depth profile, and to determine limits in identifying small objects as a function of their size. In accordance with the theory, we discover a significant advantage of the 1/f noise pattern (pink noise) for fast depth lock-in and fine detail detection, showing that such patterns are optimal choices for autostereogram design. PMID- 26831767 TI - Ray and wave aberrations revisited: a Huygens-like construction yields exact relations. AB - The aberrations of an optical system can be described in terms of the wave aberrations, defined as the departure from the ideal spherical wavefront; or the ray aberrations, which are in turn the deviations from the paraxial ray intersections measured in the image plane. The classical connection between the two descriptions is an approximation, the error of which has, to our knowledge, so far not been quantified analytically. We derive exact analytical equations for computing the wavefront surface, the aberrated ray directions, and the transverse ray aberrations in terms of the wave aberrations (OPD) and the reference sphere. We introduce precise conditions for a function to be an OPD function, show that every such function has an associated wavefront, and study the error arising from the classical approximation. We establish strict conditions for the error to be small. We illustrate our results with numerical simulations. Our results show that large numerical apertures and OPD functions with strong gradients yield larger approximation errors. PMID- 26831765 TI - Association between two CHRNA3 variants and susceptibility of lung cancer: a meta analysis. AB - Genome-wide association studies (GWAS) have identified two CHRNA3 polymorphisms (rs578776 and rs938682) associated with lung cancer risk. Furthermore, these polymorphisms were investigated and genotyped by PCR analysis. All eligible case control studies published up to Mar 1st 2015 were identified by searching Pubmed and Embase database. Negative association between rs578776-T allele and risk of lung cancer was obtained without obvious heterogeneity (OR: 0.83, 95% CI: 0.79 0.86; p = 0.898 for Q test). Rs938682-C allele carriers had a 12% to 28% decreased risk. Genotype model analysis showed results of dominant model for rs578776 (OR with 95% CI: 0.839(0.718-0.981)), dominant model for rs938682 (OR with 95% CI: 0.778(0.663-0.912)) and homozygous model for rs938682 (OR with 95% CI: 0.767(0.708-0.831)) were statistically significant. Subgroup analysis indicated rs578776-T variant had protective effect in Smokers, Caucasians, two histology subgroups, and two match subgroups. Meanwhile, rs938682-C allele was associated with decreased risk in Smokers, Caucasians, Lung cancer, and two match subgroups. Meta-regression suggested ethnicity might be the major source of heterogeneity in allele model and homozygous model for rs938682. Moreover, smoking status might contribute to part of heterogeneity under allele model. In summary, this meta-analysis suggested both rs578776 and rs938682 were significantly associated with the susceptibility of lung cancer. PMID- 26831768 TI - Numerical analysis of the harmonic components of the Bragg wavelength content in spectral responses of apodized fiber Bragg gratings written by means of a phase mask with a variable phase step height. AB - The influence of the complex interference patterns created by a phase mask with variable diffraction efficiency in apodized fiber Bragg grating (FBGs) formation on their reflectance spectra is studied. The effect of the significant contributions of the zeroth and higher (m>+/-1) diffraction orders on the Bragg wavelength peak and its harmonic components is analyzed numerically. The results obtained for Gaussian and tanh apodization profiles are compared with similar data calculated for a uniform grating. It is demonstrated that when an apodized FBG is written using a phase mask with variable diffraction efficiency, significant enhancement of the harmonic components and a reduction of the Bragg wavelength peak in the grating spectral response are observed. This is particularly noticeable for the Gaussian apodization profile due to the substantial contributions of phase mask sections with relatively small phase steps in the FBG formation. PMID- 26831769 TI - Interferometric imaging with three objectives. AB - We propose a microscope that utilizes three high numerical aperture objectives to image a sample from multiple angles, interferometrically combining the fields from each objective to obtain a higher resolution and more isotropic point-spread function than standard wide-field and confocal techniques. The proposed microscope utilizes three 0.9 NA objectives with large working distance and, therefore, has both a large imaging volume and an effective 2.7 NA. The FWHM of the point-spread function is 135 nm in the plane of the objectives, a factor of 2 better than the lateral resolution with a single objective. Out of plane, the PSF is equivalent to that of a conventional microscope. Here, we introduce the theoretical framework for evaluating the performance of the microscope and use that framework to quantitatively compare our proposed microscope to existing techniques in confocal and wide-field implementations. PMID- 26831770 TI - Increasing color saturation by optimizing light spectra constrained on color rendering properties. AB - Enhancing the color saturation of objects via illumination with specially designed light spectra is promising in many commercial and scientific applications. Existing literature has focused on studying the colors that can be rendered by white light with various correlated color temperatures, and by the mixed light from various monochromatic light-emitting diodes. However, very little literature has been devoted to methods that can actively configure the light spectrum to enhance the color saturation of an arbitrary object. This paper proposes an optimization-based method to extend the gamut that can be achieved by a given polychromatic lamp toward a chosen direction, i.e., to increase the saturation of a specific color. Moreover, to trade-off the increased saturation of a color sample with the reduced colorfulness of other samples, constraints with tunable thresholds are imposed to the optimization problem to bound the variation of a contrast color sample. In addition, the effect of uncontrollable ambient light can be taken into account by mild modifications of the optimization problem. Simulation results show that the optimized light spectrum can effectively enhance the saturation of any specific color, while maintaining the other rendered colors as intact as possible. Visual experiments have also been conducted with 22 human subjects, whose responses agree with the simulation results. PMID- 26831772 TI - Two-dimensional nonseparable discrete linear canonical transform based on CM-CC CM-CC decomposition. AB - As a generalization of the 2D Fourier transform (2D FT) and 2D fractional Fourier transform, the 2D nonseparable linear canonical transform (2D NsLCT) is useful in optics and signal and image processing. To reduce the digital implementation complexity of the 2D NsLCT, some previous works decomposed the 2D NsLCT into several low-complexity operations, including 2D FT, 2D chirp multiplication (2D CM), and 2D affine transformations. However, 2D affine transformations will introduce interpolation error. In this paper, we propose a new decomposition called CM-CC-CM-CC decomposition, which decomposes the 2D NsLCT into two 2D CMs and two 2D chirp convolutions. No 2D affine transforms are involved. Simulation results show that the proposed methods have higher accuracy, lower computational complexity, and smaller error in the additivity property compared with the previous works. Plus, the proposed methods have a perfect reversibility property, meaning that one can reconstruct the input signal/image losslessly from the output. PMID- 26831771 TI - Method for estimating closed-form solutions of the light diffusion equation for turbid media of any boundary shape. AB - This paper reports a method of estimating an approximate closed-form solution to the light diffusion equation for any type of geometry involving Dirichlet's boundary condition with known source location. It is based on estimating the optimum locations of multiple imaginary point sources to cancel the fluence at the extrapolated boundary by constrained optimization using a genetic algorithm. The mathematical derivation of the problem to approach the optimum solution for the direct-current type of diffuse optical systems is described in detail. Our method is first applied to slab geometry and compared with a truncated series solution. After that, it is applied to hemispherical geometry and compared with Monte Carlo simulation results. The method provides a fast and sufficiently accurate fluence distribution for optical reconstruction. PMID- 26831773 TI - Fast image enhancement method for display images in ambient light. AB - Display images under high illumination may appear to have lower lightness and attenuated contrast. In this paper, we review the image degradation phenomenon in ambient light through photoreceptor physiology. The influence of different environmental parameters and their effects on various gray areas in images can be evaluated by the cone response difference. Based on this, we propose a fast global tone mapping method to minimize the cone response difference at different pixel intensity levels of images displayed at different illumination levels. This method has a superior computational efficiency and higher evaluation score than existing algorithms. PMID- 26831774 TI - Polarization characteristics of objects in long-wave infrared range. AB - Research on polarization characteristics of objects has become indispensable in the field of target detection. Though widespread studies on applying polarization to target detection and material identification exist, theoretical descriptions have varied widely in accuracy and completeness. Incomplete descriptions of polarization characteristics invariably result in poor demonstration of changes caused by macroscopic influence factors. For objects that are of finite surface, a comprehensive model is built to analyze the polarization characteristics of their thermal emission. With the Stokes theory and the superposition principle of light waves, the relation between the degree of linear polarization and the spatial geometrical parameters, such as the detection distance and the shape of objects, is discussed in the long-wave infrared range in detail. This model can be applied to analyze the linear polarization characteristics among different materials. PMID- 26831775 TI - Perturbation methods to track wireless optical wave propagation in a random medium. AB - We consider certain problems in optical wave propagation in linear and nonlinear media in a regime of low-level atmospheric refractive index fluctuations. The perturbation theory hinges on the identification of such perturbing parameters to study its effect on the characteristics of the propagating free-space optical beam. Here, we illustrate the application of the few perturbation methods that are used to track the distorted traversing free-space optical fields. Furthermore, the tracking error is computed for the various approximate solutions in contrast to the numerical solution for comparing the capturing efficiency of the different perturbative analytical techniques. We found that the coordinate straining method efficiently reduces the deviation in the approximate solutions as compared to the regular perturbation expansion method. Furthermore, from the result analysis, it is observed that the tracking reliability of the various approximation solutions for a particular perturbation level depends on the proper choice of the approximation method and the order of the solution. PMID- 26831776 TI - Correlation-induced changes of the degree of paraxiality of a partially coherent beam. AB - The degree of paraxiality (DOP) is a quantification of how paraxial (or nonparaxial) a light field is. In this article, we study the DOP of a partially coherent beam with a nonconventional spatial correlation function and explore the correlation-induced changes of the DOP. Analytical expressions for the DOP and the far-field divergence angle of a generalized multi-Gaussian correlated Schell model (MGCSM) beam are derived. The properties of the DOP and the far-field divergence angle for the first type and the second type of generalized MGCSM beams without and with truncation in free space are illustrated numerically, and we find that the DOP and far-field divergence angle are closely related with the distribution of the correlation function. Modulation of the correlation function provides a novel way for modulating the nonparaxial properties of a partially coherent beam. PMID- 26831777 TI - Symmetry relationships for multiple scattering of polarized light in turbid spherical samples: theory and a Monte Carlo simulation. AB - This paper presents a theory describing totally incoherent multiple scattering of turbid spherical samples. It is proved that if reciprocity and mirror symmetry hold for single scattering by a particle, they also hold for multiple scattering in spherical samples. Monte Carlo simulations generate a reduced effective scattering Mueller matrix, which virtually satisfies reciprocity and mirror symmetry. The scattering matrix was factorized by using the symmetric decomposition in a predefined form, as well as the Lu-Chipman polar decomposition, approximately into a product of a pure depolarizer and vertically oriented linear retarding diattenuators. The parameters of these components were calculated as a function of the polar angle. While the turbid spherical sample is a pure depolarizer at low polar angles, it obtains more functions of the retarding diattenuator with increasing polar angle. PMID- 26831778 TI - Analyzing the relationship between decorrelation time and tissue thickness in acute rat brain slices using multispeckle diffusing wave spectroscopy. AB - Novel techniques in the field of wavefront shaping have enabled light to be focused deep inside or through scattering media such as biological tissue. However, most of these demonstrations have been limited to thin, static samples since these techniques are very sensitive to changes in the arrangement of the scatterers within. As the samples of interest get thicker, the influence of the dynamic nature of the sample becomes even more pronounced and the window of time in which the wavefront solutions remain valid shrinks further. In this paper, we examine the time scales upon which this decorrelation happens in acute rat brain slices via multispeckle diffusing wave spectroscopy and investigate the relationship between this decorrelation time and the thickness of the sample using diffusing wave spectroscopy theory and Monte Carlo photon transport simulation. PMID- 26831779 TI - Antimicrobial activity of a quaternized BODIPY against Staphylococcus strains. AB - A novel BODIPY derivative was designed for biomedical applications. Its mono quaternized structure ensured its water-solubility and suitable amphiphilicity. Showing no singlet oxygen generation to avoid damage to healthy cells, this new derivative proved to be an extremely promising antimicrobial agent, with activity equal or superior to ampicillin against MRS Staphylococcus strains with no short term resistance issue. Its activity against MSS Staphylococcus strains was largely superior to those of ampicillin and reached the activity of vancomycin against MSS S. epidermidis. This latter result is in particular extremely promising for the treatment of hospital-acquired infections. Also the fluorescence properties of BODIPY allowed imaging of the uptake. PMID- 26831780 TI - Physical and physiological demands of U-19 basketball refereeing: Aerobic and anaerobic demands. AB - OBJECTIVES: This study aimed to examine the physical and physiological demands of basketball refereeing. METHODS: 16 elite-level basketball referees were studied during U-19 basketball games (n=8) for time-motion analyses, exercise heart rates (HR) and blood lactate concentration [La]. Game activities were considered as time spent and distance covered in five locomotors activities (standing, walking, jogging, running and sprinting). RESULTS: Referees spent more time (p<0.01) walking (63.72+/-2.02 min) than jogging (3.10+/-0.29 min), running (4.24+/-0.46 min) and sprinting (1.69+/-0.24 min). Referees covered more distance (p<0.01) walking than jogging, running and sprinting across the quarters (Q). Mean HR (74.89+/-6.86 %HRmax) was not significantly different across the game Q (Q1 to Q4) and halves. [La] did not show significant changes (p=0.221) when comparing the half-time (4.30+/-3.92 mmol.L(-1)) and the end of the game (6.70+/-4.90 mmol.L(-1)). CONCLUSION: In light of this study, we conclude that U-19 basketball refereeing is a moderate intensity activity where referees spent 81% of total game time at low-intensity with bouts of high-intensity activities throughout the game. PMID- 26831781 TI - The making of ring currents. AB - Benzene, planar cyclooctatetraene, and borazine have been taken into account as archetypal aromatic, anti-aromatic, and non-aromatic systems. Then, the making of the pi-electron diatropic ring current of benzene, huge paratropic ring current of planar cyclooctatetraene, and weak diatropic ring current of borazine, has been monitored by means of DFT calculations of current density maps and bond current strengths along a concerted, highly symmetric reaction pathway for the trimerization and tetramerization of acetylene to benzene and planar cyclooctatetraene and the trimerization of the simplest iminoborane (BH2N) to borazine. Besides, a simple model is presented that permits to infer the presence of a ring current only on account of the sum of homotropic local vortices. The model works satisfactorily for borazine and surely as well for benzene with a substantial difference. On the one hand, for borazine, the evolution of the current density along the formation reaction can be recast summing three virtually unchanged diatropic current loops with respect to parent iminoborane molecules. On the other hand, the benzene ring current is an emerging property that can be re-elaborated as the sum of three diatropic current loops of increased diatropicity with respect to parent acetylene molecules, i.e., the radius of the maximum current increases form 0.76 to 0.97 A and the current strength increases from 3.6 to 6.7 nA T(-1). In these terms, the difference between the aromatic benzene and non-aromatic borazine can be understood as the attitude of the acetylene molecules to form always wider and stronger current loops as they get closer, a behavior not shared by the iminoborane molecules. For planar cyclooctatetraene, the paratropic circulation arising from the HOMO-LUMO transition makes the model inapplicable, since the initial hypothesis of homotropic circulations over the reaction coordinate is violated. In a sense, the fact that the model works only for a bit of the planar cyclooctatetraene formation reaction is itself distinctive of the anti-aromatic magnetic response. PMID- 26831783 TI - [Promotion of Drug Discovery Research by Utilizing Omics Technology]. PMID- 26831784 TI - [Challenge to the Development of Molecular Targeted Therapy against a Novel Target Candidate Identified by Antibody Proteomics Technology]. AB - Disease proteomics that systemically analyzes and identifies differentially expressed proteins between healthy and diseased samples is a potentially useful approach for obtaining target proteins for drug development. To date, however, very few target proteins have been identified from this field. A key issue that remains to be resolved is how to correctly identify target proteins from a number of potential candidates. To circumvent this problem, we have developed "antibody proteomics technology" in which a single chain Fv phage antibody library is utilized for proteome analysis. Here, we describe the application of this technology by primarily focusing on Eph receptor A10 (EphA10), a novel breast cancer-related protein that is a promising target for antibody drugs. To establish an effective and safe targeted cancer therapy, it is important that the target is specifically expressed in cancer tissues. Therefore, we attempted to analyze the EphA10 expression profiles. Tissue microarray analysis showed that EphA10 was expressed in all subtypes of breast cancer containing triple negative breast cancer cases. On the other hand, EphA10 was only expressed in testis tissue among 36 kinds of normal tissues. Thus, EphA10 could be a highly cancer specific protein, making it a promising target for female breast cancer patients. Finally, we examined the anti-tumor effect by anti-EphA10 antibody, aiming for the development of a novel EphA10 targeting therapy. Administration of the antibody showed that tumor volumes were significantly inhibited. Our results suggest that targeting EphA10 in breast cancer cases might be a promising new form of therapy. PMID- 26831782 TI - Effective pore size and radius of capture for K(+) ions in K-channels. AB - Reconciling protein functional data with crystal structure is arduous because rare conformations or crystallization artifacts occur. Here we present a tool to validate the dimensions of open pore structures of potassium-selective ion channels. We used freely available algorithms to calculate the molecular contour of the pore to determine the effective internal pore radius (r(E)) in several K channel crystal structures. r(E) was operationally defined as the radius of the biggest sphere able to enter the pore from the cytosolic side. We obtained consistent r(E) estimates for MthK and Kv1.2/2.1 structures, with r(E) = 5.3-5.9 A and r(E) = 4.5-5.2 A, respectively. We compared these structural estimates with functional assessments of the internal mouth radii of capture (r(C)) for two electrophysiological counterparts, the large conductance calcium activated K channel (r(C) = 2.2 A) and the Shaker Kv-channel (r(C) = 0.8 A), for MthK and Kv1.2/2.1 structures, respectively. Calculating the difference between r(E) and r(C), produced consistent size radii of 3.1-3.7 A and 3.6-4.4 A for hydrated K(+) ions. These hydrated K(+) estimates harmonize with others obtained with diverse experimental and theoretical methods. Thus, these findings validate MthK and the Kv1.2/2.1 structures as templates for open BK and Kv-channels, respectively. PMID- 26831785 TI - [Functional Analysis of GATA4 Complex, a Cardiac Hypertrophy-response Transcriptional Factor, Using a Proteomics Approach]. AB - Various stresses on the heart, such as myocardial infarction and hemodynamic overload, activate the sympathetic nervous system and the renin-angiotensin system, ultimately reach the nuclei of cardiomyocytes, and change the pattern of gene expression associated with cardiac hypertrophy. Although present pharmacological therapy for heart failure targets such extracellular molecules, mortality due to heart failure is still high. A zinc finger protein, GATA4, is one of the hypertrophy-responsive transcription factors, forms a functional protein complex with an intrinsic histone acetyltransferase, p300, and regulates pathological cardiac hypertrophy. Disruption of this complex results in the inhibition of cardiac hypertrophy and heart failure in vivo. To establish a more effective therapy for heart failure, we have been analyzing a common nuclear pathway within cardiomyocytes. We identified 73 GATA4 binding proteins by tandem affinity purification and mass spectrometric analysis. Noble GATA4 binding partners, such as cyclin-dependent kinase-9 (Cdk9: the core factor of positive transcription elongation factor b) and retinoblastoma-association protein 48/46 (RbAp48/46: the co-repressor complexes containing HDAC1/2), regulate the p300/GATA4-mediated signaling pathway and hypertrophic responses. Further analysis of p300/GATA4 complex is expected to identify target molecules for heart failure therapy. PMID- 26831786 TI - [Screening for Potential Drug Targets by Comprehensive Identification of Disease specific Antigens Incorporated into Immune Complexes in Patients with Immunological Diseases]. AB - Our immune system resembles an intelligent security system, which continually monitors for foreign invaders (infectious diseases); however, in some cases, this system recognizes healthy parts as something harmful or foreign and then attacks them (autoimmune diseases). The defining characteristics of an autoimmune disease are the existence of T- and B-cell autoreactivity against self proteins (autoantigens). In addition to autoimmune diseases, aberrant host proteins that occur during a certain state of diseases (e.g., cancer) can be recognized as an autoantigen. Immune complexes (ICs) are produced during an immune response and may reflect some aspects of an ongoing immune response. Therefore, the identity of antigens incorporated into ICs provides the information that in the future may aid in the development of diagnosis and treatment strategies for autoimmune diseases, infection, cancer, and transplantation therapy, and this information might be more relevant than information on free antigens. We developed a novel proteomic strategy (immune complexome analysis) in which ICs are separated from serum, followed by direct tryptic digestion and nano-liquid chromatography-tandem mass spectrometry for the identification and profiling of antigens in circulating ICs. We applied this strategy to the analysis of circulating ICs in autoimmune diseases (rheumatoid arthritis, anti-neutrophil cytoplasmic antibody-associated vasculitis, Takayasu's arteritis, mixed connective tissue disease, dermatomyositis, Sjogren's syndrome, systemic scleroderma, and systemic lupus erythematosus), infectious diseases and cancers. In this review, we mainly discuss the results for autoimmune diseases. PMID- 26831787 TI - [Application of Imaging Mass Spectrometry for Drug Discovery]. AB - Imaging mass spectrometry (IMS) can reveal the distribution of biomolecules on tissue sections. In this process, the biomolecules are directly ionized within tissue sections using matrix-assisted laser desorption/ionization, and then their distribution is visualized by pseudo-color based on the relative signal intensity. The biomolecules, such as fatty acids, phospholipids, glycolipids, peptides, proteins, and neurotransmitters, have been analyzed at a spatial resolution of 5 MUm. A special instrument for IMS analysis was developed by Shimadzu. The IMS analysis does not require the labeling of biomolecules and is capable of analyzing all the ionized biomolecules. Interest in this method has expanded to many research fields, including biology, agriculture, medicine, and pharmacology. The technique is especially relevant to the drug discovery process. As practiced currently, drug discovery is expensive and time consuming, requiring the preparation of probes for each drug and its metabolites, followed by systematic probe tracking in animal models. The IMS technique is expected to overcome these drawbacks by revealing the distribution of drugs and their metabolites using only a single analysis. In this symposium, I introduced the methodology and applications of IMS and discussed the feasibility of its application to drug discovery in the near future. PMID- 26831788 TI - [Structural Pharmacology for Receptors and Transporters]. PMID- 26831789 TI - [Structural Analyses of Toll-like Receptor Sensing Single-stranded Nucleic Acids and Its Application]. AB - Toll-like receptors (TLRs) are a family of pattern-recognition receptors that recognize microbial components and initiate subsequent immune responses. TLR7 and TLR8 recognize single-stranded (ss)RNA and initiate innate immune responses. Moreover, several small-molecule compounds have been identified as TLR7 and TLR8 activators. We determined the crystal structures of unliganded and ligand-induced activated human TLR8 dimers. Upon ligand stimulation, the TLR8 dimer was reorganized such that the two C-termini were brought into proximity. Ligand binding induces reorganization of the TLR8 dimer, which enables downstream signaling processes. To elucidate how TLR8 recognizes its natural ligand, ssRNA, as well as how the receptor can be activated by ssRNA that is structurally and chemically very different from the chemical ligands, we performed crystallographic studies of TLR8 in complex with ssRNA. TLR8 recognizes, at distinct sites, uridine and small oligonucleotides derived from the degradation of ssRNA. Uridine bound the site on the dimerization interface where small chemical ligands are recognized, whereas short oligonucleotides bound a newly identified site. Based on structural information, new compounds have been developed. We describe the crystal structure of a newly developed agonist, C2 butyl furo[2,3-c]quinolone. PMID- 26831790 TI - [Structural Life Science towards the Regulation of Selective GPCR Signaling]. AB - G protein-coupled receptors (GPCRs) are the largest family of receptors in the human genome. They are involved in many diseases and also the target of approximately 30% of all modern medicinal drugs. GPCRs respond to a broad spectrum of chemical entities, ranging from photons, protons, and calcium ions to small organic molecules (including odorants and neurotransmitters), peptides, and glycoproteins. Many GPCRs are members of closely related subfamilies that respond to the same hormone or neurotransmitter. However, they have different physiologic functions based on the cells in which they are expressed and the different signaling pathways that they exploit (e.g., coupling through heterotrimeric G proteins such as Gs, Gi, and Gq, as well as beta-arrestins). Antibody fragments including Fab and Fv can effectively stabilize and crystallize membrane proteins. However, using the mouse hybridoma technology it has been difficult to develop monoclonal antibodies that can recognize conformational epitopes of native GPCRs. We have recently succeeded in developing antibodies against native GPCRs using this technology in combination with our improved immunization and screening methods. In this symposium review, I present a successful example of prostaglandin E2 receptor (one of the GPCRs) crystallization using antibody fragments. To avoid several adverse effects of current therapeutics, it is essential to understand the molecular mechanism of GPCR signaling in a monomeric, dimeric, or oligomeric state. Also, we are interested in selectively regulating GPCR signaling via functional antibodies developed using our methods and/or the designed small organic molecules depending on the GPCR structure. PMID- 26831791 TI - [Structural and Functional Studies on Photoactive Retinal Proteins: Light Becomes Drugs with Proteins]. AB - Retinal proteins possess vitamin A aldehyde (retinal) as a chromophore within seven transmembrane alpha-helices. Visible light absorption of them triggers trans-cis photoisomerization of the retinal chromophore and induces structural changes in the protein moiety, resulting in a variety of biological functions such as vision, ion transportation, and photosensing. Environmental genomics revealed that retinal proteins are widely distributed through all three biological kingdoms, eukarya, bacteria, and archaea, indicating the biological significance of their light energy conversion. In addition to their biological aspect, retinal proteins have become a focus of interest in part because of applications for optogenetics. On the basis of our results and other findings, we highlight the recent progress in structural and functional studies on retinal proteins. PMID- 26831792 TI - [In Vitro Selected Macrocyclic Peptides: Tools for Regulating the Conformational Freedom of Transmembrane Proteins]. AB - Membrane proteins allow a cell to communicate with its environment by relaying a signal or transporting a molecule through the cell membrane. Elucidation of the three-dimensional structure of a membrane protein provides a greater understanding of its function and mechanisms. Ultimately, this knowledge will enlighten researchers on how these proteins can be regulated to elicit a desired cellular response, which could lead to novel therapeutic medicine. Unfortunately, the determination of the high-resolution crystal structures of transmembrane proteins remains a challenge due to their poor solubility and high conformational flexibility. Additives and cocrystallization ligands are being used to address these problems. In vitro selected macrocyclic peptides have recently been successfully employed as cocrystallization ligands. Although originally intended as inhibitors and drug lead molecules, in vitro selected macrocyclic peptides are now showing that their pharmacodynamic properties also allow them to serve as excellent cocrystallization ligands. Structures for macrocyclic peptide-bound transporters, the multidrug and toxic compound extrusion family transporter from Pyrococcus furiosus (PfMATE) and the ABC transporter subfamily B member 1 from Cyanidioschyzon meraloe (CmABCB1), have been elucidated using X-ray crystallography. The cocrystal structures reveal that the macrocyclic peptides improve crystallization by binding in a similar manner as a small molecule or a biologic. The PfMATE-binding macrocyclic peptides MaD3S and MaD5 bind to the surfaces buried in the center channel of the transporters. Although both transporters possess a center channel and substrate-binding pocket, the CmABCB1 binding macrocyclic peptide, aCAP, binds to the outer surface of the transporter in a similar manner to a biologic. PMID- 26831793 TI - [Structural and Pharmacological Studies of an ABC Multidrug Transporter]. AB - A drug's effectiveness against a disease depends not only on its interaction with receptors but also its pharmacokinetics (absorption, distribution, metabolism, and extrusion; ADME). ATP binding cassette (ABC) multidrug transporters are important proteins that influence the ADME properties of a drug, especially the ABC transporter subfamily B member 1 (ABCB1). Elucidation of the molecular mechanisms of ABCB1 will contribute to our understanding of the molecular basis of ADME. Human ABCB1 is expressed in many organelles, and exports various substrates from cells using energy generated by its ATP hydrolase (ATPase) activity. The ATPase activity depends on the concentration of the transport substrates, and the characteristic behavior of the substrate-dependent ATPase activity can be related to the molecular mechanism of ABCB1. Recently, we have revealed the molecular mechanisms of a eukaryotic ABCB1 homolog, CmABCB1, based on structural and functional studies. In this review, I discuss the relationship between key structural features and the behavior of transport substrate-dependent ATPase activity of CmABCB1, including its role in determining the molecular basis of ADME. PMID- 26831794 TI - [The Challenge of Developing New Treatments for NTDs Originating from Japan]. PMID- 26831795 TI - [Current Trend of Drug Development for Neglected Tropical Diseases (NTDs)]. AB - EBOLA hemorrhagic fever, a typical emerging infectious disease, began in December 2013 in the southern part of Guinea, and killed more than 11000 people by the end of June, 2015. In addition to emerging/re-emerging diseases and the 3 major infectious diseases i.e. HIV/AIDS, tuberculosis and malaria, neglected tropical diseases (NTDs) have recently become important tropical diseases of the poor. It is remarkable that Japan succeeded in the eradication of malaria and other tropical diseases, which include lymphatic filariasis and schistosomiasis. However, despite these achievements, it is important to sustain our efforts when we consider global health. This review highlights the significance of elimination and/or control of NTDs, and then introduces the current situation of drug development activities in Japan, which are aimed towards combating tropical infectious diseases. They include studies on a novel drug target, the "mitochondrial NADH-fumarate reductase system (Fumarate respiration)" composed of complex I, rhodoquinone and complex II, which plays an important role in the anaerobic energy metabolism of many helminths such as Ascaris suum. An additional interesting finding highlighted herein is that ascofuranone, a recently developed anti-African trypanosome drug, shows specific inhibition of fumarate respiration in Echinococcus multilocularis mitochondria. PMID- 26831796 TI - [International Partnership for Therapeutic Drug Development of NTDs by DNDi]. AB - The Drugs for Neglected Diseases initiative (DNDi), with headquarters in Geneva, is a non-profit drug research and development (R&D) organization and Product Development Partnership (PDP) which was established in 2003 by 7 founding organizations such as Medecins Sans Frontieres (MSF), the Pasteur Institute, The Specific Programme for Research and Training in Tropical Diseases (WHO-TDR), etc. DNDi has worked mainly on the development of new treatments for neglected tropical diseases (NTDs), which is difficult to achieve under market economy conditions. DNDi has promoted overall drug discovery research including the screening of drug candidates, hit to lead, lead optimization, pre-clinical and clinical studies in the area of infectious diseases with a focus on malaria, sleeping sickness (human African trypanosomiasis; HAT), Chagas disease, leishmaniasis, filarial diseases and pediatric formulations for HIV treatment. DNDi's achievements include the development of novel therapies based on patient needs through innovative partnerships with over 130 organizations in industry, government, academia, and public institutions around the world. To date, DNDi has registered 6 novel treatments adapted to the needs of patients in poor countries, and has another 12 novel entities in development. DNDi Japan is a Japanese non profit organization (NPO) based on the global principles of DNDi and, as the only PDP in Japan, is supporting NTD drug discovery projects in collaboration with Japanese pharmaceutical companies, academic institutions and government agencies by utilizing Japan's excellent R&D capabilities to develop new treatments for NTDs in order to contribute to global health. PMID- 26831797 TI - [Development and Distribution of Drugs for NTDs: Efforts of One Pharmaceutical Company]. AB - The Pharmaceutical Industry is expected to play a proactive global role in combatting neglected tropical diseases (NTDs) and other tropical diseases affecting low-income countries. Such a role would include novel medicine R&D, manufacturing and distribution. In order to succeed in this role, several challenges need to be overcome: a) the economic challenge or cost benefit balance for the development of these medicines, and b) sparse in-house experience with these diseases within the Industry. During the last decade, the Product Development Partnership (PDP) model has become an effective strategy to address such challenges. Organizations such as the Medicines for Malaria Venture (MMV), Drugs for Neglected Diseases initiative (DNDi), TB alliance, PATH (formerly the Program for Appropriate Technology in Health), and others have linked pharmaceutical companies, funding organizations, academic researchers and others, and have thus been able to successfully populate treatment pipelines directed at NTDs, Malaria, tuberculosis (TB), and human immunodeficiency virus (HIV)/AIDS. In this paper, our experience working with one of these organizations, DNDi, is described. We have been collaborating with DNDi in evaluating the actions of Eisai's antifungal compound, E1224, in a clinical study for treating Chagas Disease. In addition, other Eisai initiatives directed at NTDs and improving patients' access to medicines are introduced. PMID- 26831798 TI - [Activity of NTDs Drug-discovery Research Consortium]. AB - Neglected tropical diseases (NTDs) are an extremely important issue facing global health care. To improve "access to health" where people are unable to access adequate medical care due to poverty and weak healthcare systems, we have established two consortiums: the NTD drug discovery research consortium, and the pediatric praziquantel consortium. The NTD drug discovery research consortium, which involves six institutions from industry, government, and academia, as well as an international non-profit organization, is committed to developing anti protozoan active compounds for three NTDs (Leishmaniasis, Chagas disease, and African sleeping sickness). Each participating institute will contribute their efforts to accomplish the following: selection of drug targets based on information technology, and drug discovery by three different approaches (in silico drug discovery, "fragment evolution" which is a unique drug designing method of Astellas Pharma, and phenotypic screening with Astellas' compound library). The consortium has established a brand new database (Integrated Neglected Tropical Disease Database; iNTRODB), and has selected target proteins for the in silico and fragment evolution drug discovery approaches. Thus far, we have identified a number of promising compounds that inhibit the target protein, and we are currently trying to improve the anti-protozoan activity of these compounds. The pediatric praziquantel consortium was founded in July 2012 to develop and register a new praziquantel pediatric formulation for the treatment of schistosomiasis. Astellas Pharma has been a core member in this consortium since its establishment, and has provided expertise and technology in the area of pediatric formulation development and clinical development. PMID- 26831799 TI - [Industry, Academia and Government Partnership through the Global Health Innovative Technology Fund (GHIT)]. AB - In developing countries, many people are unable to access basic healthcare services, resulting in many avoidable deaths and/or disabilities. The United Nations adopted the Millennium Development Goals in order to resolve this problem, and Japan has been contributing greatly to the achievement of these goals. In this context, in 2013 the Government of Japan proposed its Strategy on Global Health Diplomacy, and since then has been promoting Universal Health Coverage. Since the beginning of the 21st century, the particular importance of addressing neglected tropical diseases (NTDs) has been stressed by the international community. Nevertheless, of the 1 billion people world-wide who are currently living with NTDs, about three-fourths of these are living in poverty, and of these, nearly 65% are unable to acquire or access drugs for the prevention and treatment of these diseases. Under these circumstances, Japan decided to support the Global Health Innovative Technology (GHIT) Fund in order to support the research and development of drugs for people in developing countries, as well as the manufacture, supply and administration of these drugs. Over the last two years, the GHIT Fund has been supporting the research and development of five new candidate drugs for three NTDs (Chagas disease, leishmaniasis and malaria). Japan also hopes to stimulate domestic pharmaceutical industries in developing countries, as well as to increase international cooperation through various activities such the utilization of our capacity to research and develop new drugs. PMID- 26831800 TI - [Establishment for the Supporting of Pharmacies as the Healthcare Information Hub in the Community]. PMID- 26831801 TI - [Current Status of Community Pharmacies: Expectations as a Health Information Hub, the Enforcement of Revised Pharmaceutical and Medical Device Act, and a New Role as Stakeholders]. AB - According to the "Japan Revitalization Strategy" established in June 2013, "the government will promote better contributions of local pharmacies and pharmacists in encouraging self-medication of citizens by making pharmacies the community based hub for providing information, giving advice on the proper use of non prescription drugs, etc. and offering consultation and information service concerning health". In addition, the "Demanded Function and Ideal Form of Pharmacy," published in January 2014, requested a change, from pharmacies that specialized in dispensing medicines to pharmacies that serve as whole healthcare stations, providing pharmaceutical care based on patients' medical history, including the intake of dietary supplements. The medication fee was revised in April 2014 to enhance family pharmacy services and the management of pharmaceutical care. At that time, blood testing at a registered pharmacy was officially allowed under strict regulation. Revision of the "Pharmacist Law" in June 2014 included a request to pharmacists to provide pharmaceutical advice in addition to information. For the mitigation of drug-induced tragedies, the "Pharmaceutical Affairs Law" was amended to the "Pharmaceutical and Medical Device Act (PMD Act)" in November 2014, and proper use of medicines was imposed on healthcare professionals and other stakeholders. Patients were also requested to learn and understand the safety and harmful effects of medicines, and were requested to use medicines appropriately. As mentioned above, the status of pharmacies and pharmacists has dramatically changed in the past 2 years, and such changes over time are required. PMID- 26831802 TI - [Japanese Model of Asheville Project. Its Overview and Initiative]. AB - The Asheville Project(r) began in 1996 in Asheville, North Carolina, where community pharmacists, in collaboration with physicians, provide health coaching to patients with lifestyle diseases to accomplish their improved self-management of the disease. The project has now widely expanded across the United States. With periodical coaching by pharmacists, according to the reports of these programs, patients have been reported to show improvements in self-management and laboratory data, including the number of doctor visits, medication adherence and the number of foot examinations. Economically, the total medical costs for this disease have decreased 34% over a 5-year period by complying with the Asheville Project. In implementing this model in Japan, various questions, such as the feasibility for busy pharmacists to expend 30-60 min for meeting individually with patients, effective collaboration between pharmacy and physician, patients' acceptance of support by pharmacists to modify their behavior, etc. had to be answered. Thus, we developed a program entitled, "A Health Coaching Program by Community Pharmacists in a Collaborative Practice," aimed at preventing the aggravation of lifestyle diseases; we evaluated its feasibility for the above mentioned concerns. The content of this coaching program has been prepared with reference to the Asheville Project(r) and with the support of Kitasato University School of Pharmacy and the Iowa Pharmacy Association, USA. We herein introduce this coaching program, as well as what the pharmacists have learned through this program. PMID- 26831803 TI - [Pilot Study of "Japanese Model of Asheville Project"~How Did It Work?]. AB - For prevention of the aggravation of diabetic nephropathy, a treatment method that combines self-care with medical guidance is becoming increasingly important, leading to the development of programs for lifestyle modification for the patients. To assess the effectiveness of such programs, we have conducted a feasibility study of a patient self-care support program with medical collaboration by registered pharmacists in community pharmacies involving patients with diabetic nephropathy who are under treatment at medical institutions, including our hospital. This study evaluated the two primary measurements, which are A) the actual execution rate versus planned programs, and B) the patient satisfaction rate. In addition, the achievement rate of behavioral objectives, satisfaction rate of diabetes treatment, degree of concerns (Diabetes Treatment Satisfaction Questionnaire; DTSQ, Problem Areas in Diabetes; PAID) and other physiological indicators have been evaluated. With the approval of the IRB at Kitasato University, sixteen out of 18 patients have continued to participate in the support program, and the study has shown high patient satisfaction with pharmacist coaching support. Patients have gained interest in managing their lifestyles, thereby increasing self-efficacy. Also, information shared between the pharmacists and the physicians has clarified patients' issues and concerns pertaining to their lifestyles, which were effectively utilized in the coaching program. Through meetings with pharmacists, patients have been reassured of the expertise of the pharmacist and thus gained mutual trust, which leads to the patient's behavioral change. We believe that the collaboration of patients, pharmacists and physicians has resulted in effective team-based patient care. PMID- 26831804 TI - [Estimation of the Health Status of People in the Vicinity of Pharmacies Using Pharmacy Big Data]. AB - The purpose of this study was to propose a method for visualizing the patterns of the geographical propagation of influenza infection, and to elaborate parameters for the characterization of these patterns. First, a motion picture was prepared for the quotidian propagation of influenza infection in the Greater Tokyo Metropolitan area, which is considered a typical epidemic area for the 2012/2013 flu season. Second, hebdomadal recordings of patients with influenza infection in the 47 prefectures of Japan were grouped into 3 categories (1-peak, 2-peak, or multi-peak). The prefectures were arranged according to the weeks with the maximum number of patients, to examine variations in the temporal infection order of the districts among the flu seasons. These characteristics were analyzed using Cramer's coefficient of association and Spearman's rank correlation coefficient. Finally, the propagation of influenza infection was compared between urban and remote areas: the Greater Tokyo Metropolitan area and Tochigi prefecture. Regarding influenza virus infection, differences in population density, public transportation systems, and lifestyles between the urban and rural areas were found to lead to distinct endemic patterns of infection. Emphasis was placed on the so-called big data hubris. PMID- 26831805 TI - [Development of an Informative System for Consumers and Pharmacists Aimed at the Proper Use of Kampo OTCs]. AB - Kampo medicines must be used according to an individual's physical characteristics and symptoms to avoid lack of efficacy, adverse reactions or interactions with other drugs. As category-2 over-the-counter drugs (OTCs), Kampo OTCs are not targets of active explanations by pharmacists, and consumers usually decide to use OTCs by themselves on the basis of drug label information. However, information on the label is occasionally brief. To promote the proper use of Kampo OTCs, we herein propose an informative tool based on the Australian Shelf Talker (information on the proper use of OTCs with a self-check questionnaire for consumers), the Self-Check Card (SCC). We also prepared the informative material, Information to the Pharmacist (IP), directed at pharmacists regarding these Kampo OTCs. We created SCCs and IPs for 16 prescriptions in the 5 most demanded categories (cold, cough/sore throat, urination problems, women's diseases, and shoulder stiffness or joint/nerve pain). The SCC with questions in a simplified language specifies individuals who should avoid the drug, or those who should consult a pharmacist before purchase, according to the safety information on the respective drug labels. The IP provides information to pharmacists on safety issues and those concerning recognition of the consumer's symptoms and physical characteristics needed for the selection of appropriate Kampo OTCs. Such SCCs and IPs are now in use in 2 pharmacies to know pharmacists' suggestions about improvements and consumer's opinions and degree of satisfaction. We believe these risk-benefit communication tools, SCC and IP, will contribute to improve the proper use of Kampo OTCs. PMID- 26831806 TI - [For the Establishment of an Informative Support Framework in Pharmacies: Informative Support System for Diabetes]. AB - According to the Japanese revitalization strategy endorsed by the government in June, 2013, pharmacies are expected to play an active role as the hub of health information. But this is not sufficiently organized: an infrastructure for providing neutral information which becomes the basis of such health information is not yet established for healthcare professionals, patients and consumers. As for drug information available subsequent to the marketing of pharmaceutical products, information from the pharmaceutical companies including Package Inserts and Interview-forms are often found. However, though such information from companies is important, it is necessary for healthcare professionals and patients to have access to the information evaluated by a trustworthy third party. With overseas distribution, the dissemination of drug information is provided by third parties, which are independent of regulatory agencies. For example, National Health Service (NHS) Evidence in the UK offers wide-ranging information based on evidence from a disease to pharmaceutical products, and is a widely available information source for healthcare professionals, patients and consumers. With regard to therapeutic medications, drug information and health foods in the Japanese community, it is necessary for patients and healthcare professionals that we establish neutral and common systematic information based on the research evidence. By providing information on the Internet, which enables people to access the information easily and to assess a product's usefulness objectively, we hope to eventually develop a system that ensures a patient's safety in the use of drugs. PMID- 26831807 TI - [Role of Transient Receptor Potential Channels in Paclitaxel- and Oxaliplatin induced Peripheral Neuropathy]. AB - Peripheral neuropathy is a common adverse effect of paclitaxel and oxaliplatin treatment. The major dose-limiting side effect of these drugs is peripheral sensory neuropathy. The symptoms of paclitaxel-induced neuropathy are mostly sensory and peripheral in nature, consisting of mechanical allodynia/hyperalgesia, tingling, and numbness. Oxaliplatin-induced neurotoxicity manifests as rapid-onset neuropathic symptoms that are exacerbated by cold exposure and as chronic neuropathy that develops after several treatment cycles. Although many basic and clinical researchers have studied anticancer drug-induced peripheral neuropathy, the mechanism is not well understood. In this review, we focus on (1) analysis of transient receptor potential vanilloid 1 (TRPV1) channel expression in the rat dorsal root ganglion (DRG) after paclitaxel treatment and (2) analysis of transient receptor potential ankyrin 1 (TRPA1) channel in the DRG after oxaliplatin treatment. This review describes that (1) paclitaxel-induced neuropathic pain may be the result of up-regulation of TRPV1 in small- and medium diameter DRG neurons. In addition, paclitaxel treatment increases the release of substance P, but not calcitonin gene-related peptide, in the superficial layers of the spinal dorsal horn. (2) TRPA1 expression via activation of p38 mitogen activated protein kinase in small-diameter DRG neurons, at least in part, contributes to the development of oxaliplatin-induced acute cold hyperalgesia. We suggest that TRPV1 or TRPA1 antagonists may be potential therapeutic lead compounds for treating anticancer drug-induced peripheral neuropathy. PMID- 26831808 TI - [Structure and Function of the Nuclear Receptor Constitutive Androstane Receptor]. AB - Animal defense mechanisms against both endogenous and exogenous toxic compounds function mainly through receptor-type transcription factors, including the constitutive androstane receptor (CAR). Following xenobiotic stimulation, CAR translocates into the nucleus and transactivates its target genes including oxygenic and conjugative enzymes and transporters in hepatocytes. We identified subcellular localization signals in the rat CAR: two nuclear localization signals (NLS1 and 2); two nuclear export signals (NES1 and 2); and a cytoplasmic retention region. The nuclear import of CAR is regulated by the importin-Ran system and microtubule network. Five splice variants (SV1-5) were identified in rat liver in addition to wild-type CAR. When expressed in immortalized cells, their artificial transcripts were inactive as transcription factors. A CAR mutant with three consecutive alanine residues inserted into the ligand-binding domain of CAR showed ligand-dependent activation of target genes in immortalized cells, which is in marked contrast to the constitutive transactivating nature of wild type CAR. Using this assay system, androstenol and clotrimazole, both of which are inverse agonists of CAR, were classified as an antagonist and weak agonist, respectively. A member of the DEAD box DNA/RNA helicase family (DP97) and protein arginine methyltransferase 5 (PRMT5) were found to be gene (or promotor)-specific coactivators of CAR. The expression of the CAR gene might be under the control of clock genes mediated by the nuclear receptor Rev-erb-alpha. PMID- 26831809 TI - [Diversity of Plants Belonging to the Genus Ligularia (Asteraceae) Based on Terpenoids and Synthetic Studies on Some Terpenoids]. AB - The terpenoid constituents of Ligularia virgaurea (30 samples), Ligularia pleurocaulis (8 samples), Ligularia dictyoneura (8 samples), Ligularia brassicoides (5 samples), Ligularia lingiana (1 sample), and Ligularia liatroides (1 sample)(all belonging to section Senecillis of Ligularia, Asteraceae and collected in Yunnan, Sichuan, Qinghai, and Gansu provinces, China), from which 220 compounds were isolated, including 113 novel ones, are reviewed. Five chemotypes were identified in L. virgaurea based on their chemical constituents, while three clades were detected from the base sequences. Although intra-specific diversity was found in L. virgaurea, more samples were needed of other species in order to reach a definite conclusion. Inter-specific diversity was also examined in section Senecillis but was restricted due to the scarcity of samples. Synthetic studies on chiral natural products to determine their absolute configurations, especially those of riccardiphenols A and B as well as crispatanolide, which were all isolated from the liverwort, are briefly reviewed. PMID- 26831810 TI - [Study of Supplementary Analgesics Capable of Reducing the Dosage of Morphine]. AB - Morphine with its potent analgesic property has been widely used for the treatment of various types of pain. However, the intrathecal (i.t.) administration of morphine at doses far higher than those required for antinociception exhibited nociceptive-related behaviors consisting of scratching, biting and licking, hyperalgesia, and allodynia in mice. Morphine-3-glucuronide (M3G), one of the major metabolites of morphine, has been found to evoke nociceptive behaviors similar to those after high-dose i.t. morphine. It is plausible that M3G may be responsible for nociception seen after high-dose i.t. morphine treatment. This article reviews the potential mechanism of spinally mediated nociceptive behaviors evoked by i.t. M3G in mice. We discuss the possible presynaptic release of nociceptive neurotransmitters/neuromodulators such as substance P, glutamate, dynorphin, and Leu-enkephalin in the primary afferent fibers following i.t. M3G administration. It is possible to speculate that i.t. M3G could indirectly activate NK1, NMDA, and delta2-opioid receptors that lead to the release of nitric oxide (NO) in the dorsal spinal cord. The major function of NO is the production of cGMP and the activation of protein kinase G (PKG). The NO-cGMP-PKG pathway plays an important role in M3G-induced nociceptive behavior. The phosphorylation of extracellular signal-related kinase (ERK) in the dorsal spinal cord was also evoked via the NO-cGMP-PKG pathway through the activation of delta2-opioid, NK1, and NMDA receptors, contributing to M3G-induced nociceptive behaviors. The demonstration of a neural mechanism underlying M3G-induced nociception provides a pharmacological basis for improved pain management with morphine at high doses. PMID- 26831811 TI - [Implementation and Evaluation of Genetic Testing Seminars on Lifestyle-related Disease Prevention for Pharmacy Students]. AB - The field of pharmacotherapy has advanced to use molecular targeted agents, and pharmacists are now encouraged to focus on pharmacogenomics. A seminar titled "Implementation and evaluation of genetic testing of lifestyle-related disease genes" was presented to students at the Faculty of Pharmaceutical Sciences, Hiroshima University, describing the pharmacogenomic role of single nucleotide polymorphisms in obesity-related genes and alcohol metabolism-related genes. The seminar topic was selected first because pharmaceutical students were already familiar with some of the content, and secondly because we believe that pharmacists should be informed about the prevention of lifestyle-related diseases using genetic testing. We evaluated the usefulness of this seminar by administering a questionnaire before and after the seminar to participating students. Several points requiring improvement were identified, although 82% of students stated that the seminar was "very useful" or "useful". We conclude that this educational seminar was useful to students of pharmaceutical sciences. PMID- 26831812 TI - [Pharmacists' Behavior in Clinical Practice: Results from a Questionnaire Survey of Pharmacy Students]. AB - A questionnaire survey was performed to obtain pharmacy students' impressions of pharmacists' behavior, to classify these based on professionalism, and to analyze the relationship between these experiences and students' satisfaction with their clinical practice in Japan. The questionnaire was answered by 327 5th-year pharmacy school students upon completing clinical practice at community pharmacies from 2011 to 2012. They rated their satisfaction with their clinical practice using a 6-point Likert scale, and provided descriptions of their experience such as, "This health provider is professional", or "What a great person he/she is as a health provider". We counted the words and then categorized the responses into 10 traits, as defined by the American Pharmaceutical Association Academy of Students of Pharmacy-American Association of Colleges of Pharmacy, Council of Deans Task Force on Professionalism 1999, using text mining. We analyzed the relationship between their experiences with respectful persons, and satisfaction, using the Mann-Whitney U-test (significance level<0.05). Most students (337 of 364, 92.6%) reported experiences with respectful health providers. These students experienced significantly more satisfaction than did other students (p<0.001). We analyzed 343 sentences written by 261 students, using text mining analysis after excluding unsuitable responses. The word most used was "patient" (121 times). Many students noted their impression that the pharmacists had answered patients' questions. Of the 10 trait categories, "professional knowledge and skills" was mentioned most often (151 students). PMID- 26831813 TI - Diagnostic and Prognostic Value of Circulating Tumor Cells in Head and Neck Squamous Cell Carcinoma: a systematic review and meta-analysis. AB - Several techniques have been developed to detect circulating tumor cells (CTC) in patients with head and neck squamous cell carcinoma (HNSCC), but their diagnostic and prognostic value are not yet fully established. A computerized retrieval of literatures was conducted without time restrictions using the electronic database in December 2014. Diagnostic accuracy variables were pooled and analyzed by the Meta-DiSc software. Engauge Digitizer and Stata software were used for pooled survival analysis. Twenty-two retrieved studies were eligible for systematic review, of which 9 conformed for the diagnostic test meta-analysis and 5 for the prognostic analysis. Subgroup analysis showed 24.6% pooled sensitivity and 100% pooled specificity of detections by using positive selection strategy, which moreover presented low heterogeneity. The presence of CTC was significantly associated with shorter disease free survival (DFS, HR 4.62, 95% CI 2.51-8.52). In conclusion, current evidence identifies the CTC detection assay as an extremely specific, but low sensitive test in HNSCC. Also, the presence of CTC indicates a worse DFS. PMID- 26831815 TI - CHALLENGES FACED IN TRANSFERRING ECONOMIC EVALUATIONS TO MIDDLE INCOME COUNTRIES. AB - BACKGROUND: Decision makers in middle-income countries are using economic evaluations (EEs) in pricing and reimbursement decisions for pharmaceuticals. However, whilst many of these jurisdictions have local submission guidelines and local expertise, the studies themselves often use economic models developed elsewhere and elements of data from countries other than the jurisdiction concerned. The objectives of this study were to describe the current situation and to assess the challenges faced by decision makers in transferring data and analyses from other jurisdictions. METHODS: Experienced health service researchers in each region conducted an interview survey of representatives of decision making bodies from jurisdictions in Asia, Central and Eastern Europe, and Latin America that had at least 1 year's experience of using EEs. RESULTS: Representatives of the relevant organizations in twelve countries were interviewed. All twelve jurisdictions had developed official guidelines for the conduct of EEs. All but one of the organizations evaluated studies submitted to them, but 9 also conducted studies and 7 commissioned them. Nine of the organizations stated that, in evaluating EEs submitted to them, they had consulted a study performed in a different jurisdiction. Data on relevant treatment effect was generally considered more transferable than those on prices/unit costs. Views on the transferability of epidemiological data, data on resource use and health state preference values were more mixed. Eight of the respondents stated that analyses submitted to them had used models developed in other jurisdictions. Four of the organizations had a policy requiring models to be adapted to reflect local circumstances. The main obstacles to transferring EEs were the different patterns of care or wealth of the developed countries from which most economic evaluations originate. CONCLUSIONS: In middle-income countries it is commonplace to deal with the issue of transferring analyses or data from other jurisdictions. Decision makers in these countries face several challenges, mainly due to differences in current standard of care, practice patterns, or gross domestic product between the developed countries where the majority of the studies are conducted and their own jurisdiction. PMID- 26831816 TI - Recent similarity in distribution ranges does not mean a similar postglacial history: a phylogeographical study of the boreal tree species Alnus incana based on microsatellite and chloroplast DNA variation. AB - We reconstructed the historical pattern of postglacial biogeographic range expansion of the boreal tree species Alnus incana in Europe. To assess population genetic structure and diversity, we performed a combined analysis of nuclear microsatellite loci and chloroplast DNA sequences (65 populations, 1004 individuals). Analysis of haplotype and microsatellite diversity revealed that southeastern refugial populations situated in the Carpathians and the Balkan Peninsula did not spread north and cannot be considered as important source populations for postglacial recolonization of Europe; populations in Eastern Europe did not establish Fennoscandian populations; populations in Fennoscandia and Eastern Europe have no unique genetic cluster, but represent a mix with a predominant cluster typical for Central Europe; and that colonization of Fennoscandia and Eastern Europe took place from Central Europe. Our findings highlight the importance of an effective refugium in Central Europe located outside classical southern refugia confirming the existence of northern refugia for boreal trees in Europe. The postglacial range expansion of A. incana did not follow the model established for Picea abies. Fennoscandian populations are not derived from Eastern European ones, but from Central European ones. PMID- 26831817 TI - Preclinical Abuse Potential Assessment of Flibanserin: Effects on Intracranial Self-Stimulation in Female and Male Rats. AB - INTRODUCTION: Flibanserin is a serotonin receptor subtype 1A agonist and 2A antagonist that has been approved by the Food and Drug Administration for treating female sexual interest and arousal disorder. Little is known about the abuse potential of flibanserin. AIM: To examine abuse-related effects of flibanserin in rats using an intracranial self-stimulation (ICSS) procedure previously used to evaluate the abuse potential of other drugs. METHODS: Adult female and male Sprague-Dawley rats with electrodes implanted in the medial forebrain bundle were trained to press a lever for electrical brain stimulation under a "frequency-rate" ICSS procedure. In this procedure, increasing frequencies of brain stimulation maintain increasing rates of responding. Drugs of abuse typically increase (or "facilitate") ICSS rates and produce leftward and upward shifts in ICSS frequency-rate curves, whereas drugs that lack abuse potential typically do not alter or only decrease ICSS rates. Initial studies determined the potency and time course of effects on ICSS produced by acute flibanserin administration (1.0, 3.2 and 10.0 mg/kg). Subsequent studies determined the effects of flibanserin (3.2-18 mg/kg) before and after a regimen of repeated flibanserin administration (5.6 mg/kg/d for 5 days). Effects of the abused stimulant amphetamine (1.0 mg/kg) were examined as a positive control. MAIN OUTCOME MEASURES: Flibanserin effects on ICSS frequency-rate curves in female and male rats were examined and compared with the effects of amphetamine. RESULTS: Baseline ICSS frequency-rate curves were similar in female and male rats. Acute and repeated administrations of flibanserin produced only decreases in ICSS rates, and rate-decreasing effects of the highest flibanserin dose (10 mg/kg) were greater in female than in male rats. In contrast to flibanserin, amphetamine produced an abuse-related increase in ICSS rates that did not differ between female and male rats. CONCLUSION: These results suggest that flibanserin has low abuse potential. In addition, this study suggests that female rats might be more sensitive than male rats to the rate-decreasing effects of high flibanserin doses. PMID- 26831818 TI - Incidence of and Risk Factors For Post-Intubation Hypotension in the Critically Ill. AB - BACKGROUND: We aim to report the incidence of post-intubation hypotension in the critically ill, to report in-hospital mortality and length of stay in those who developed post-intubation hypotension, and to explore possible risk factors associated with post-intubation hypotension. MATERIAL/METHODS: Adult (>=18 years) ICU patients who received emergent endotracheal intubation were included. We excluded patients if they were hemodynamically unstable 60 minutes pre intubation. Post-intubation hypotension was defined as the administration of any vasopressor within 60 minutes following intubation. RESULTS: Twenty-nine patients developed post-intubation hypotension (29/147, 20%). Post-intubation hypotension was associated with increased in-hospital mortality (11/29, 38% vs. 19/118, 16%) and length of stay (21 [10-37] vs. 12 [7-21] days) on multivariate analysis. Three risk factors for post-intubation hypotension were identified on multivariate analysis: 1) decreasing mean arterial pressure pre-intubation (per 5 mmHg decrease) (p-value=0.04; 95% CI 1.01-1.55); 2) administration of neuromuscular blockers (p-value=0.03; 95% CI 1.12-6.53); and 3) intubation complication (p-value=0.03; 95% CI 1.16-15.57). CONCLUSIONS: Post-intubation hypotension was common in the ICU and was associated with increased in-hospital mortality and length of stay. These patients were more likely to have had lower mean arterial pressure prior to intubation, received neuromuscular blockers, or suffered a complication during intubation. PMID- 26831814 TI - Annual Research Review: Enduring neurobiological effects of childhood abuse and neglect. AB - BACKGROUND: Childhood maltreatment is the most important preventable cause of psychopathology accounting for about 45% of the population attributable risk for childhood onset psychiatric disorders. A key breakthrough has been the discovery that maltreatment alters trajectories of brain development. METHODS: This review aims to synthesize neuroimaging findings in children who experienced caregiver neglect as well as from studies in children, adolescents and adults who experienced physical, sexual and emotional abuse. In doing so, we provide preliminary answers to questions regarding the importance of type and timing of exposure, gender differences, reversibility and the relationship between brain changes and psychopathology. We also discuss whether these changes represent adaptive modifications or stress-induced damage. RESULTS: Parental verbal abuse, witnessing domestic violence and sexual abuse appear to specifically target brain regions (auditory, visual and somatosensory cortex) and pathways that process and convey the aversive experience. Maltreatment is associated with reliable morphological alterations in anterior cingulate, dorsal lateral prefrontal and orbitofrontal cortex, corpus callosum and adult hippocampus, and with enhanced amygdala response to emotional faces and diminished striatal response to anticipated rewards. Evidence is emerging that these regions and interconnecting pathways have sensitive exposure periods when they are most vulnerable. CONCLUSIONS: Early deprivation and later abuse may have opposite effects on amygdala volume. Structural and functional abnormalities initially attributed to psychiatric illness may be a more direct consequence of abuse. Childhood maltreatment exerts a prepotent influence on brain development and has been an unrecognized confound in almost all psychiatric neuroimaging studies. These brain changes may be best understood as adaptive responses to facilitate survival and reproduction in the face of adversity. Their relationship to psychopathology is complex as they are discernible in both susceptible and resilient individuals with maltreatment histories. Mechanisms fostering resilience will need to be a primary focus of future studies. PMID- 26831819 TI - E2F1/TS Immunophenotype and Survival of Patients with Colorectal Cancer Treated with 5FU-Based Adjuvant Therapy. AB - The predictive value of thymidylate synthase (TS) expression alone for 5FU-based treatment of colorectal cancer (CRC) has not been clinically confirmed. Little is known on the association of expression of E2F1, which controls the transcription of genes encoding proteins engaged in DNA synthesis including TS, and survival of patients with CRC. The purpose of this study is to assess the correlation between expression of both E2F1 and TS in CRCs and survival of patients administered adjuvant 5FU-based chemotherapy, in order to find a better predictor of treatment outcome than expression of TS or E2F1 alone. Nuclear TS and E2F1 were detected by immunohistochemistry in tissue microarrays from 190 CRCs (Astler-Coller stage B2 or C). Multivariate analysis identified significant association of the combined E2F1+TS+ immunophenotype with worse OS (HR = 3,78, P = 0,009) and DFS (HR = 2,30, P = 0,03) of patients with colon cancer. There were significant differences between E2F1+TS+ and E2F1-TS- Kaplan-Meier survival curves in relation to DFS (P = 0.008) and OS (P = 0.01). About 37 and 31 % difference in 3-year DFS and OS respectively were seen between patients with E2F1+TS+ vs. E2F1-TS- colon cancer immunophenotype. The E2F1+TS+ immunophenotype may be a marker of poor prognosis (the worst DFS and OS) of patients with colon cancer treated with 5FU-based adjuvant therapy. A subgroup of patients with this immunophenotype may require different and perhaps more aggressive treatment than 5FU-based chemotherapy. Thus, the combined E2F1/TS immunophenotype could be a potential indicator of colon cancer sensitivity to 5FU. PMID- 26831820 TI - The enantioselective construction of chiral spirooxindole-based 4-thiazolidinone via asymmetric catalytic formal [3+2] annulation using a bifunctional catalyst. AB - 4-Thiazolidinone is regarded as a privileged structural unit in bioactive compounds. However, there is still no example of a catalytic method for the synthesis of chiral 4-thiazolidinone until now. We reported herein a facile and efficient method for the construction of chiral spirooxindole-based 4 thiazolidinone. This methodology is based on the asymmetric formal [3+2] annulation of 1,4-dithiane-2,5-diol to ketimines which is followed by simple oxidation, featuring a broad substrate scope with high enantioselectivity (up to 98% ee). The method has been successfully applied to the synthesis of a novel class of mycobacterium tuberculosis inhibitor-spirooxindole based 4 thiazolidinone. PMID- 26831821 TI - Comparison of Antithyroglobulin Antibody Concentrations Before and After Ablation with 131I as a Predictor of Structural Disease in Differentiated Thyroid Carcinoma Patients with Undetectable Basal Thyroglobulin and Negative Neck Ultrasonography. AB - BACKGROUND: Patients with differentiated thyroid carcinoma are submitted to a first assessment several months after initial therapy to evaluate their response to treatment. At that assessment, measurement of basal thyroglobulin (Tg) and antithyroglobulin antibodies (TgAb) and neck ultrasonography (US) are recommended. Serum Tg may be falsely negative in the presence of TgAb, and the management of patients with negative Tg but positive TgAb represents a challenge. The objective of this study was to correlate the variation in TgAb concentrations (comparison before and after ablation with (131)I) with the risk of structural disease. METHODS: The sample consisted of 116 low- or intermediate-risk patients who had undetectable Tg, negative US at initial assessment, and positive TgAb 8 12 months after thyroidectomy and ablation with (131)I. RESULTS: Comparison of TgAb concentrations before and after ablation with (131)I showed a reduction of >50% in 56 patients (group A), a reduction of <50% in 35 patients (group B), and an increase in 25 patients (group C). Metastases were detected in 5/116 (4.3%) patients during initial assessment (lymph nodes in two, pulmonary in two, and bone in one). They were diagnosed in 0/56, 2/35 (5.7%), and 3/25 (12%) patients of groups A, B, and C, respectively. During follow-up, metastases were detected in 7/111 (6.3%) patients (lymph nodes in six, and pulmonary in one). They occurred in 1/56 (1.8%), 3/33 (9%), and 3/22 (13.6%) patients of groups A, B, and C, respectively. Thus, structural disease was found in 1.8%, 14.3%, and 24% of groups A, B, and C, respectively. This rate was 4% in low-risk patients and 15.4% in intermediate-risk patients. CONCLUSIONS: Among patients with undetectable Tg, negative US, and positive TgAb after ablation with (131)I, the frequency of structural disease was <5% in patients, with >50% reduction in TgAb. Among patients without a significant reduction in TgAb, approximately 10% of low-risk patients and >20% of intermediate-risk patients had structural disease. These results help define the indication for imaging methods other than US during initial assessment and long-term follow-up. PMID- 26831823 TI - [Adult colocolonic intussusception due to adenomatous polyp: An exceptional cause of a rare entity]. PMID- 26831824 TI - Hepatolithiasis. Surgical approach using endoscopic holmium laser for treatment. PMID- 26831822 TI - Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs. AB - T lymphocytes are essential contributors to the adaptive immune system and consist of multiple lineages that serve various effector and regulatory roles. As such, precise control of gene expression is essential to the proper development and function of these cells. Previously, we identified Snai2 and Snai3 as being essential regulators of immune tolerance partly due to the impaired function of CD4(+) regulatory T cells in Snai2/3 conditional double knockout mice. Here we extend those previous findings using a bone marrow transplantation model to provide an environmentally unbiased view of the molecular changes imparted onto various T lymphocyte populations once Snai2 and Snai3 are deleted. The data presented here demonstrate that Snai2 and Snai3 transcriptionally regulate the cellular fitness and functionality of not only CD4(+) regulatory T cells but effector CD8(alpha+) and CD4(+) conventional T cells as well. This is achieved through the modulation of gene sets unique to each cell type and includes transcriptional targets relevant to the survival and function of each T cell lineage. As such, Snai2 and Snai3 are essential regulators of T cell immunobiology. PMID- 26831825 TI - Attitudes towards depression, psychiatric medication and help-seeking intentions amid financial crisis: Findings from Athens area. AB - BACKGROUND: The financial crisis has yielded adverse effects on the population worldwide, as evidenced by elevated rates of major depression. International recommendations for offsetting the mental health impact of the recession highlight the need for effective treatment, including reduction in the stigma attached to the disorder. AIMS: This study endeavoured to explore lay attitudes to depression and psychiatric medication during a period of financial crisis and to identify their correlates. Furthermore, it investigated their link to help seeking intentions. METHOD: A random and representative sample of 621 respondents from Athens area participated in the study (Response Rate = 81.7%). The telephone interview schedule consisted of the Personal Stigma Scale, a self-constructed scale tapping attitudes to psychiatric medication and one question addressing help-seeking intentions. RESULTS: The preponderant stigmatising belief about depression pertains to perceiving the disorder as a sign of personal weakness. In addition, stereotypes of unpredictability and dangerousness were popular among the sample. Nonetheless, stigmatising beliefs are much stronger with regard to psychiatric medication; perceived as addictive, capable of altering one's personality, less effective than homeopathic remedies and doing more harm than good. Help-seeking intentions were predicted by education, unemployment and attitudes to psychiatric medication solely. CONCLUSION: Research on the mental health effects of the global recession should encompass studies investigating the stigma attached to mental disorders and its implications. PMID- 26831826 TI - Uses of strength-based interventions for people with serious mental illness: A critical review. AB - BACKGROUND: For the past 3 decades, mental health practitioners have increasingly adopted aspects and tools of strength-based approaches. Providing strength-based intervention and amplifying strengths relies heavily on effective interpersonal processes. AIM: This article is a critical review of research regarding the use of strength-based approaches in mental health service settings. The aim is to discuss strength-based interventions within broader research on recovery, focussing on effectiveness and advances in practice where applicable. METHOD: A systematic search for peer-reviewed intervention studies published between 2001 and December 2014 yielded 55 articles of potential relevance to the review. RESULTS: Seven studies met the inclusion criteria and were included in the analysis. The Quality Assessment Tool for Quantitative Studies was used to appraise the quality of the studies. Our review found emerging evidence that the utilisation of a strength-based approach improves outcomes including hospitalisation rates, employment/educational attainment, and intrapersonal outcomes such as self-efficacy and sense of hope. CONCLUSION: Recent studies confirm the feasibility of implementing a high-fidelity strength-based approach in clinical settings and its relevance for practitioners in health care. More high-quality studies are needed to further examine the effectiveness of strength based approaches. PMID- 26831827 TI - Verbal Fluency in Parkinson's Patients with and without Bilateral Deep Brain Stimulation of the Subthalamic Nucleus: A Meta-analysis. AB - OBJECTIVES: Patients with Parkinson's disease often experience significant decline in verbal fluency over time; however, deep brain stimulation of the subthalamic nucleus (STN-DBS) is also associated with post-surgical declines in verbal fluency. The purpose of this study was to determine if Parkinson's patients who have undergone bilateral STN-DBS have greater impairment in verbal fluency compared to Parkinson's patients treated by medication only. METHODS: A literature search yielded over 140 articles and 10 articles met inclusion criteria. A total of 439 patients with Parkinson's disease who underwent bilateral STN-DBS and 392 non-surgical patients were included. Cohen's d, a measure of effect size, was calculated using a random effects model to compare post-treatment verbal fluency in patients with Parkinson's disease who underwent STN-DBS versus those in the non-surgical comparison group. RESULTS: The random effects model demonstrated a medium effect size for letter fluency (d=-0.47) and a small effect size for category fluency (d=-0.31), indicating individuals with bilateral STN-DBS had significantly worse verbal fluency performance than the non surgical comparison group. CONCLUSIONS: Individuals with Parkinson's disease who have undergone bilateral STN-DBS experience greater deficits in letter and category verbal fluency compared to a non-surgical group. PMID- 26831828 TI - Response and Adverse Effects of Nilotinib in Imatinib-Resistant Chronic Myeloid Leukemia Patients: Data From a Developing Country. PMID- 26831829 TI - Drug Information Services Today: Current Role and Future Perspectives in Rational Drug Therapy. AB - Polypharmacy and complex drug treatment regimens are becoming increasingly common, which may lead to adverse drug reactions, drug interactions, medication nonadherence, and increasing costs and thus challenge the rational use of drugs. At the same time, the accessibility of drug information increases, and health care professionals may have limited opportunities and capabilities to search and critically evaluate drug information. Clinicians have reported difficulties in searching the best evidence and translating study findings into clinically meaningful information applicable to specific patients. Consequently, it remains a challenge to ensure the rational use of drugs in the years to come. Drug information centers (DICs) have been established to promote the rational use of drugs. One of the most important tasks of DICs is the question and answer services for health care professionals posing drug-related questions. DICs staffed by pharmacists and clinical pharmacologists hold expertise in searching for drug information and critical evaluation of the literature. The uniqueness in this service lies not only in the identification and interpretation of the scientific literature but also in the adaptation of the findings into specific clinical situations and the discussion of possible solutions with the enquirer. Thus, DICs could provide valuable decision support to the clinic. Taking into account the increasing number of possible drug-related questions that will arise today and in the future, the DICs will remain highly relevant in the years to come. However, the DICs must follow the developments in health information technology to disseminate relevant, unbiased drug information to old and new users of the service. Moreover, the DICs are important tools to counterbalance the drug information published by the pharmaceutical industry. PMID- 26831831 TI - Persistent current in a correlated quantum ring with electron-phonon interaction in the presence of Rashba interaction and Aharonov-Bohm flux. AB - Persistent current in a correlated quantum ring threaded by an Aharonov-Bohm flux is studied in the presence of electron-phonon interactions and Rashba spin-orbit coupling. The quantum ring is modeled by the Holstein-Hubbard-Rashba Hamiltonian and the energy is calculated by performing the conventional Lang-Firsov transformation followed by the diagonalization of the effective Hamiltonian within a mean-field approximation. The effects of Aharonov-Bohm flux, temperature, spin-orbit and electron-phonon interactions on the persistent current are investigated. It is shown that the electron-phonon interactions reduce the persistent current, while the Rashba coupling enhances it. It is also shown that temperature smoothens the persistent current curve. The effect of chemical potential on the persistent current is also studied. PMID- 26831830 TI - Crosstalk between chloroplast thioredoxin systems in regulation of photosynthesis. AB - Thioredoxins (TRXs) mediate light-dependent activation of primary photosynthetic reactions in plant chloroplasts by reducing disulphide bridges in redox-regulated enzymes. Of the two plastid TRX systems, the ferredoxin-TRX system consists of ferredoxin-thioredoxin reductase (FTR) and multiple TRXs, while the NADPH dependent thioredoxin reductase (NTRC) contains a complete TRX system in a single polypeptide. Using Arabidopsis plants overexpressing or lacking a functional NTRC, we have investigated the redundancy and interaction between the NTRC and Fd TRX systems in regulation of photosynthesis in vivo. Overexpression of NTRC raised the CO2 fixation rate and lowered non-photochemical quenching and acceptor side limitation of PSI in low light conditions by enhancing the activation of chloroplast ATP synthase and TRX-regulated enzymes in Calvin-Benson cycle (CBC). Overexpression of NTRC with an inactivated NTR or TRX domain partly recovered the phenotype of knockout plants, suggesting crosstalk between the plastid TRX systems. NTRC interacted in planta with fructose-1,6-bisphosphatase, phosphoribulokinase and CF1 gamma subunit of the ATP synthase and with several chloroplast TRXs. These findings indicate that NTRC-mediated regulation of the CBC and ATP synthesis occurs both directly and through interaction with the ferredoxin-TRX system and is crucial when availability of light is limiting photosynthesis. PMID- 26831832 TI - Social support seeking and self-efficacy-building strategies in enhancing the emotional well-being of informal HIV/AIDS caregivers in Ibadan, Oyo state, Nigeria. AB - This study examined the relative efficacy of social support seeking (SSS) and self-efficacy building (SEB) in the management of emotional well-being of caregivers of people suffering from HIV/AIDS. It was based at the United States President's Emergency Plan for AIDS Relief (PEPFAR) center in the University College Hospital, Ibadan, Oyo state, being the first and the largest teaching hospital in Nigeria. A 3 * 2 factorial design consisting of treatment and a control group was used. The columns have two levels of gender being male and female caregivers. One-hundred and sixty-five (165) caregivers who were taking care of people that are suffering from HIV/AIDS were purposively selected and randomly assigned to the treatment groups and control. The treatment was carried out for a period of eight weeks. Two null hypotheses were tested, both at .05 levels of significance. Data were collected with the use of standardized intruments rating scale; social support scale, general self-efficacy scale and emotional well-being scale. ANCOVA was used to establish significant treatment effects with the pretest as covariate. Even though SSS and SEB were both found to be effective in enhancing the emotional well-being of informal caregivers in this study when compared to the controls, SSS was significantly more effective than SEB in achieving this goal. Since the HIV/AIDS patients cannot be adequately cared for in the hospital settings due to severe shortages of material, personnel and time, serious efforts should be made by the three levels of the health care system viz: the primary, secondary and tertiary health care systems, to encourage the employment of the psychological management of caregivers of people suffering from HIV/AIDS. Also, the psychologists, clinical psychologists and the significant others should be encouraged to employ this psychological management in the care of HIV/AIDS informal caregivers. PMID- 26831833 TI - Serotonergic Markers in Atopic Dermatitis. AB - Stress and anxiety may worsen atopic dermatitis (AD) through the serotonin system. Serotonergic expression was measured in 28 patients with AD in relation to extent of the disease (SCORing of Atopic Dermatitis; SCORAD), pruritus intensity (visual analogue scale; VAS), anxiety traits (Swedish Universities Scales of Personality; SSP) and depression (Montgomery-Asberg Depression Rating Scale-Self assessment; MADRS-S). Biopsies were taken from lesional and non lesional AD skin, and investigated for expression of serotonin, its receptors 5 HT1A and 5-HT2, and serotonin transporter protein (SERT), using immunohistochemistry. 5-HT1AR-immunoreactivity (ir) was higher in lesional skin in apical epidermis and in mast cell-like cells in dermis, and 5-HT2AR-ir in apical epidermis and on blood vessels. In contrast, a basement membrane 5-HT2AR ir signal was higher in non-lesional skin. The distribution of SERT-ir in the basal epidermal layer was higher in lesional skin. Positive and negative correlations were found between serotonergic markers and SCORAD, inflammation, pruritus intensity, anxiety traits, and depression score, indicating that serotonergic mechanisms are involved in AD. PMID- 26831834 TI - Risk Factors for Local and Distant Recurrence After Surgical Treatment in Patients With Non-Small-Cell Lung Cancer. AB - INTRODUCTION: The purpose of this study was to identify independent perioperative and pathologic variables associated with non-small-cell lung cancer (NSCLC) recurrence after complete surgical resection. PATIENTS AND METHODS: A retrospective examination was performed of a prospectively maintained database of patients who underwent resection for NSCLC from January 2009 to January 2014 at a multi-institution. Clinicopathologic variables were evaluated for their influence on frequency of recurrence. Cox proportional regression hazard model analysis examined the association of recurrence in NSCLC. RESULTS: Of these patients, 2816 (19.3%) experienced recurrence of primary cancer. Local or distant recurrence was found in 20.5% and 79.5% of patients, respectively. Median follow-up was 27.9 months (range, 11.4-66.0 months). The analysis indicated independent effects of the following risk factors on the risk of recurrence: age 64-90 years (hazard ratio [HR], 1.136; 95% confidence interval [CI] 1.024-1.261), histologic type adenocarcinoma (HR, 1.117; 95% CI 1.005-1.24), blood vessel invasion (HR, 1.236; 95% CI, 1.124-1.359), lymphatic vessel invasion (HR, 1.287; 95% CI, 1.176-1.409), visceral pleural invasion (HR, 1.641; 95% CI, 1.215-2.218), N1 disease (HR, 1.142; 95% CI, 0.99-1.316), N2 disease (HR, 1.596; 95% CI, 1.271-1.649), tumor size of 20-30 mm (HR, 1.235; 95% CI, 1.081-1.41), 30-50 mm (HR, 1.544; 95% CI, 1.33-1.792), 50-70 mm (HR, 1.521; 95% CI, 1.275-1.815), and 70-100 mm (HR, 1.71; 95% CI, 1.385-2.11), pneumonectomy (HR, 1.08; 95% CI, 0.97-1.203), and sublobar resection (HR, 1.762; 95% CI, 1.537-2.019). CONCLUSION: In the largest series reported to date on postresection recurrence of NSCLC, increasing pathologic stage, advanced age, pneumonectomy, sublobar resection, lymphatic and blood vessel invasion, and visceral pleural invasion were independently associated with local and distant recurrence. PMID- 26831835 TI - Diagnostic Value of Bronchoalveolar Lavage for Diagnosis of Suspected Peripheral Lung Cancer. AB - BACKGROUND: There is a paucity of data concerning the benefit of bronchoalveolar lavage (BAL) for the diagnosis of suspected peripheral lung cancer (PLC). The aim of this study was to investigate the diagnostic value of BAL for the diagnosis of suspected PLC. PATIENTS AND METHODS: All flexible bronchoscopies that included BAL among other modalities (brush, forceps, washing) for the diagnosis of a suspected PLC performed between 2009 and 2013 were analyzed in this retrospective study. RESULTS: A total of 260 patients were included. Malignancy was present in 61%. BAL's sensitivity for the diagnosis of malignancy was 29%, and overall diagnostic yield of BAL was 46%. However, only 1% of cancer diagnoses would have been missed in the absence of BAL. In the multivariable analysis, the size of lesion (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.02-1.33; P = .023), the presence of bronchus sign (OR, 4.73; 95% CI, 1.06-21.08; P = .042), and the presence of mediastinal/hilar lymphadenopathy (OR, 3.37; 95% CI, 1.53 7.41; P = .002) were associated with improved BAL true-positive ratio relating to diagnosis of malignancy. However, the effect of lesion size on sensitivity was small (area under the curve, 0.31; 95% CI, 0.23-0.40; P < .001). Ground-glass lesions were not associated with improved BAL diagnostic value. The number needed to test for BAL for the diagnosis of malignancy or pulmonary infection was 37. CONCLUSION: Conventional BAL has a low diagnostic value for the diagnosis of suspected PLC, and the low number needed to test does not qualify BAL as a recommended routine investigation for the diagnosis of suspected PLC for either solid or ground-glass lesions. PMID- 26831837 TI - Association of carbon monoxide levels with allergic diseases in children. AB - BACKGROUND: Air pollution is regarded as a potential reason for the development or aggravation of allergic diseases. OBJECTIVE: To investigate the relationship between exposure to outdoor air pollution during the first year of life and the development of allergic diseases, and to determine the association between outdoor air pollution near the residence and recent symptoms of allergic diseases in children. METHODS: A nationwide cross-sectional survey was conducted in 6- to 7-year-old children. Among them, subjects who had been born (n = 1828) or lived (n = 1894) within 2 km of the nearest air quality monitoring sites were selected. The prevalence of allergic diseases was assessed by using questionnaires. Each subject was examined by pediatricians to determine the presence of eczema. Publicly available data were used regarding the daily ambient concentrations of sulfur dioxide, nitrogen dioxide, ozone, carbon monoxide (CO), and particulate matter. RESULTS: For a 100 ppb increase in the mean daily CO level during the first year of life, the adjusted odds ratio for lifetime allergic rhinitis was 1.10 (95% confidence interval, 1.03-1.19). For a 1 ppm increase in the annual average CO level during the past 12 months, the adjusted odds ratio for the presence of atopic dermatitis on the day of the survey was 8.11 (95% confidence interval, 1.06-62.12). However, the other air pollutants showed no statistical significance. CONCLUSIONS: Higher exposure to CO during infancy increased the risk of development of allergic rhinitis. The risk of current atopic dermatitis symptoms increased in children who were exposed to higher CO levels during the past 12 months. PMID- 26831836 TI - The Pain Experience of Hispanic Americans: A Critical Literature Review and Conceptual Model. AB - Although the Hispanic population is a burgeoning ethnic group in the United States, little is known about their pain-related experience. To address this gap, we critically reviewed the existing literature on pain experience and management among Hispanic Americans (HAs). We focused our review on the literature on nonmalignant pain, pain behaviors, and pain treatment seeking among HAs. Pain management experiences were examined from HA patients' and health care providers' perspectives. Our literature search included variations of the term "Hispanic" with "AND pain" in PubMed, Embase, Web of Science, ScienceDirect, and PsycINFO databases. A total of 117 studies met our inclusion criteria. We organized the results into a conceptual model with separate categories for biological and/or psychological and sociocultural and/or systems-level influences on HAs' pain experience, response to pain, and seeking and receiving pain care. We also included information on health care providers' experience of treating HA patients with pain. For each category, we identified future areas of research. We conclude with a discussion of limitations and clinical implications. PERSPECTIVE: In this critical review of the literature we examined the pain and management experiences of the HA population. We propose a conceptual model, which highlights findings from the existing literature and future areas of research. PMID- 26831838 TI - Insights, strategies, asthma and allergy risk factors, and the allergist/immunologist: Challenges to be met and promises to keep! PMID- 26831839 TI - Examining causes of the urban (inner city) asthma epidemic: Implementing new management strategies. AB - Asthma in the inner city contributes to high morbidity and mortality, and, in school children, reduced school attendance and alteration in academic performance. There is a need to improve asthma care in the inner city by reducing asthma exacerbations. Methods are currently available to predict and prevent seasonal exacerbations of asthma. In addition, new medications are being developed that will be effective in improving pulmonary function and reducing asthma exacerbations. School-centered asthma programs can also be helpful to assist children and clinicians in applying asthma treatment plans and assuring optimal adherence to these plans. PMID- 26831840 TI - Antioxidant supplementation and exhaled nitric oxide in children with asthma. AB - BACKGROUND: The effect of allergen avoidance on airway inflammation is similar to that observed with treatment with inhaled steroids, whereas inhaled steroids have no effect on oxidative stress-induced inflammation. OBJECTIVE: The aim of this study was to retrospectively evaluate the potential effect of an antioxidant dietary supplement on exhaled nitric oxide over a month in pediatric patients on stable antiasthma treatment. METHODS: Forty-seven children with moderate-to severe asthma were retrospectively evaluated. All the patients were sensitive to Dermatophagoides pteronyssinus and Dermatophagoides farinae, and they were receiving the minimum inhaled corticosteroid dosage required to maintain adequate control. Within a few weeks of admission at Misurina Hospital in the Alps, the regular treatment was gradually reduced, then some children who were receiving a daily dose of inhaled corticosteroids, <=200 mcg of fluticasone propionate, were prescribed a nutraceutical dietary supplement for at least 4 weeks. Lung function and fractional exhaled nitric oxide (FeNO) measurements were recorded at the beginning and after 1 month of the dietary supplementation. RESULTS: Baseline lung function and FeNO values did not differ between the two groups of patients. After 4 weeks of nutraceutical supplementation, FeNO values decreased, from 19.00 ppb (interquartile range, 14-31 ppb) to 11.00 ppb (interquartile range, 6-23 ppb) (p = 0.03). No significant reduction was observed in the group that did not receive the supplementation, and no significant difference between groups was observed, both at baseline and after 4 weeks of nutraceutical supplementation. CONCLUSION: Supplementation with a nutraceutical of antioxidants and anti inflammatory compounds, such as curcumin, resveratrol, soy phospholipids, zinc, selenium, and vitamin D, may be associated with reduced airway inflammation, as documented by a fall in FeNO. PMID- 26831841 TI - Adrenal suppression by inhaled corticosteroids in patients with asthma: A systematic review and quantitative analysis. AB - BACKGROUND: Inhaled corticosteroids used for treating persistent asthma can suppress adrenal cortisol secretion. This inhibition of endogenous cortisol secretion is an important marker of systemic steroid activity. Although meta analyses have demonstrated a dose-dependent suppression of cortisol by inhaled corticosteroids, regardless of inhaler type, the impact of novel freon-free inhaled corticosteroid preparations has not been reviewed. OBJECTIVE: The aim of this study was to synthesize all currently available studies on novel inhaled corticosteroid preparations, including ciclesonide, beclomethasone dipropionate, budesonide, and fluticasone propionate. In particular, we aimed to compare the effect of ciclesonide on cortisol suppression with other existing preparations. METHODS: We carried out a systematic review of the medical data bases on cortisol suppression in patients due to inhaled corticosteroids. A multivariate regression model was used to determine dose-dependent relationships between each inhaled corticosteroid and cortisol suppression with respect to age, type of inhaler, and study design. RESULTS: From analysis of 64 studies identified in the review, the strongest dose-response urinary cortisol suppression was observed in patients treated with beclomethasone (8.4% per 100 MUg; p = 0.029), followed by fluticasone (3.2% per 100 MUg; p < 0.001), and budesonide (3.1% per 100 MUg; p = 0.001). No significant urinary cortisol suppression was associated with ciclesonide treatment (1.8% per 100 MUg; p = 0.267). Although ciclesonide did not affect cortisol levels, this appeared to be due to its unique pharmacokinetic properties rather than the use of a novel formulation. CONCLUSION: Our findings indicated that the introduction of novel freon-free delivery technologies for inhaled corticosteroids had not eliminated adverse adrenal suppression of cortisol secretion. PMID- 26831842 TI - Hereditary angioedema: A call for collective terminology. PMID- 26831843 TI - Differential effect of omalizumab on pulmonary function in patients with allergic asthma with and without chronic rhinosinusitis. AB - BACKGROUND: Omalizumab, an anti-immunoglobulin E monoclonal antibody, is approved by the U.S. Food and Drug Administration for the management of patients with allergic asthma and with refractory disease, and has also proven beneficial in the management of selected patients with chronic rhinosinusitis (CRS). The common airway model indicates that patients with both allergic asthma and CRS may be more challenging to manage clinically. This is the first study to evaluate the response of omalizumab in patients with asthma and CRS versus those with asthma alone. OBJECTIVE: To compare pulmonary function test (PFT) responses in omalizumab-treated patients with asthma with CRS with omalizumab-treated patients with asthma without CRS. METHODS: This was a retrospective case-control study at a tertiary university clinic. Between 2007 and 2014, a total of 259 patients with allergic asthma had been prescribed omalizumab for asthma. Outcome measures were absolute, and the percentage changes in PFT results were compared with the baseline. RESULTS: Overall, 81 patients had serial PFT results available for evaluation, among whom 59 (73%) had CRS. Average treatment duration was 27.2, 27.7, and 25.8 months for the entire sample, for patients with asthma and CRS, and for patients with asthma and without CRS, respectively. Overall, PFT metrics improved across all parameters (forced expiratory volume in 1 second, forced vital capacity, forced expiratory volume in 1 second to forced vital capacity ratio, and forced expiratory flow 25-75%). Significant improvement (p < 0.05, paired t-test) was observed for three of four metrics in patients with comorbid CRS but in none of these parameters in patients without CRS. CONCLUSION: Patients with allergic asthma who were treated with omalizumab manifested some improvement in PFT scores. CRS may add to the overall symptom burden experienced by patients with asthma, especially in those with increasing severity, but comorbid CRS did not adversely impact the therapeutic potential of omalizumab. In fact, the benefit of omalizumab was more likely to be observed in patients with asthma and with CRS than in patients with asthma and without CRS. PMID- 26831844 TI - Real-life effectiveness of budesonide/formoterol therapy in asthma: A subanalysis of the SMARTASIA study. AB - BACKGROUND: In the Study to Investigate Real Life Effectiveness of Symbicort Maintenance and Reliever Therapy in Asthma Patients Across Asia, the effectiveness of single-inhaler budesonide/formoterol maintenance and reliever therapy was evaluated in patients with poorly controlled asthma. OBJECTIVE: To study the effects of this therapy on a Chinese patient subgroup. METHODS: In this 12-week, multicenter, open-label therapeutic phase IV study, patients with partially controlled or uncontrolled asthma were switched from their usual asthma treatment to budesonide/formoterol (160/4.5 MUg, one inhalation twice daily and as needed) after a 2-week run-in period. Primary and secondary objectives of the study, asthma control and quality of life were assessed by using the five-item Asthma Control Questionnaire and the Standardized Asthma Quality of Life Questionnaire. Asthma symptom scores, study medication use, asthma control and/or symptom-free days, and the number of asthma-related nighttime awakenings were also monitored. RESULTS: In total, 478 Chinese patients were enrolled and 407 patients initiated treatment. The patients displayed a significant improvement in mean (standard deviation) five-item Asthma Control Questionnaire (-0.58 +/- 0.86; p < 0.0001) and Standardized Asthma Quality of Life Questionnaire (0.69 +/- 0.79; p < 0.0001) scores versus the run-in period. Mean (standard deviation) asthma symptom scores were significantly reduced compared with run-in (-0.30 +/- 0.55 daytime, -0.31 +/- 0.56 nighttime; p < 0.0001 for both), as was as-needed study medication use (-0.24 +/- 1.16 daytime, -0.28 +/- 0.97 nighttime; p < 0.0001 for both). Patients who received previous treatment with salmeterol/fluticasone propionate also showed improvement in asthma control. CONCLUSIONS: In China, asthma control in Chinese patients whose asthma was not fully controlled with previous standard therapy improved during 12 weeks of treatment with budesonide/formoterol maintenance and reliever therapy. Quality of life was improved, and treatment was well tolerated. (Clinical Trials identifier NCT00939341). PMID- 26831845 TI - Biomarker assessment in chronic rhinitis and chronic rhinosinusitis: Endothelin 1, TARC/CCL17, neopterin, and alpha-defensins. AB - BACKGROUND: Chronic rhinitis (CR) is characteristically divided into several major clinical phenotypes: allergic rhinitis (AR); nonallergic, noninfectious rhinopathy (NAR); and chronic rhinosinusitis (CRS). CRS has two phenotypic variants: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). An area of growing interest is to identify biologic markers that could assess different aspects of CR phenotypes. OBJECTIVE: The aim of the study was to evaluate four CR biomarkers: endothelin-1 (ET-1), thymus and activation-regulated chemokine (CCL17), neopterin, and alpha-defensins in subjects with AR, NAR, and CRS. METHODS: Fifty-one patients with AR, 43 patients with NAR, 46 patients with CRSsNP, 54 patients with CRSwNP, and 40 healthy controls were included. ET-1, TARC/CCL17, neopterin, and alpha-defensins levels in subjects' serum and nasal secretions (NS) were measured by the enzyme-linked immunosorbent assay. RESULTS: High NS levels of ET-1, TARC/CCL17, and alpha-defensins were characteristic for CRSwNP, although only high NS levels of neopterin were found in the CRSsNP phenotype. AR phenotype was characterized by high NS levels of ET-1 and TARC/CCL17. In the subjects with NAR, none of these biomarker levels in serum and NS differed from those of healthy controls. CONCLUSIONS: CR can be categorized by ET-1, TARC/CCL17, neopterin, and alpha-defensins into several disease phenotypes. Further studies are needed to better investigate pathophysiologic roles of these biomarkers in CRS. PMID- 26831846 TI - Birch allergy and oral allergy syndrome: The practical relevance of serum immunoglobulin E to Bet v 1. AB - BACKGROUND: Birch allergy (BA) may frequently be associated with fruit-vegetables oral allergy syndrome (OAS). Bet v 1 is the major birch allergen. Previously, it was reported that serum-specific immunoglobulin E (IgE) level could differentiate allergy from sensitization. Thus, this study aimed to investigate the practical role of Bet v 1 IgE. METHODS: A total of 245 subjects (128 women, 117 men; mean age, 41 years) with suspected allergic rhinitis and sensitization to Bet v 1 were evaluated. Serum IgE to Bet v 1 was assessed by using immuno-enzymatic. BA and OAS were diagnosed according to validated criteria. Symptom severity perception was measured by the visual analog scale. RESULTS: A total of 158 patients (64.5%) had BA. Patients with BA had higher serum Bet v 1 IgE levels than subjects who were sensitized (p < 0.0001). A cutoff value of 8.94 kUA/L predicted BA (area under the curve, 0.76; odds ratio, 6.18). Fifty-three patients with BA (33.5%) had OAS. Patients positive for OAS had higher Bet v 1 levels (p < 0.0001) and more-severe symptoms (p < 0.0001) than patients with BA and negative for OAS. A cutoff value of 17.4 kUA/L predicted OAS (area under the curve, 0.59; odds ratio, 3.19). CONCLUSIONS: The present study demonstrated that serum IgE levels to Bet v 1 could be a useful marker for differentiating between different birch pollen sensitization phenotypes. PMID- 26831847 TI - Dosing of European sublingual immunotherapy maintenance solutions relative to monthly recommended dosing of subcutaneous immunotherapy. AB - BACKGROUND: Recently, a series of assays has been conducted in which sublingual immunotherapy (SLIT) maintenance extracts of European manufacturers were compared with U.S. concentrated extracts by using U.S. Food and Drug Administration recommended in vitro testing. These test results have been published. We herein performed further data analysis to facilitate interpretation of SLIT dosing by U.S. physicians. OBJECTIVE: To express the allergen quantity of maintenance SLIT as recommended by European manufacturers relative to U.S. subcutaneous immunotherapy (SCIT) maintenance dosing. METHODS: We analyzed the maintenance SLIT solutions of Dermatophagoides pteronyssinus, timothy grass pollen, cat, and ragweed pollen from four European manufacturers and concentrated extracts from three U.S. manufacturers and from the U.S. Food and Drug Administration. Here, we expressed the potency of these European SLIT solutions in U.S. terms and from there calculated the monthly maintenance dose relative to the recommended monthly SCIT doses per allergen. RESULTS: Over the whole range of allergen extracts analyzed here, one of the manufacturers consistently dosed low ("EUR1," monthly SLIT dose 1-5 times the SCIT dose) and one of the manufacturers dosed high ("EUR4," monthly SLIT dose 16-237 times the SCIT dose). DISCUSSION: For more than half of the products, SLIT was not "high dose" as has originally been recommended. When reviewing the low- and high-dose products with respect to efficacy in clinical trials included in a meta-analysis on SLIT, some low-dose extracts showed efficacy. Thus, apart from the allergen dose, it might very well be possible that other factors also play an important role in determining clinical efficacy in SLIT. PMID- 26831848 TI - The value of the clinical history for the diagnosis of immediate nonsteroidal anti-inflammatory drug hypersensitivity and safe alternative drugs in children. AB - BACKGROUND: Diagnosing hypersensitivity reactions that develop as a result of nonsteroidal anti-inflammatory drugs (NSAID) with a history is mostly misleading, and skin tests and/or provocation tests are needed for a definitive diagnosis. OBJECTIVE: To determine the frequency of actual NSAID hypersensitivity and whether there are any parameters in the history to predict NSAID hypersensitivity. In addition, to determine safe alternative drugs for children who are diagnosed with actual NSAID hypersensitivity. METHODS: Children with a history of NSAID hypersensitivity were evaluated by an allergist. Safe alternatives in children with a confirmed NSAID hypersensitivity were found by oral provocation tests. RESULTS: Sixty-four patients who were admitted with a suspicion of immediate-type reaction to NSAIDs were included in the study. The median age of the patients was 6 years old (range, 1-17 years), and 37 of the patients (57.8%) were boys. We performed skin tests for suspected NSAID in 35 patients (54.7%). Of these, two had positive results. Provocation tests were performed with 62 patients whose skin test results were negative or for whom skin tests were not available. During the provocation tests, 16 patients (25.8%) developed reactions. Low- and high-dose acetaminophen, nimesulide, and tolmetin sodium were used to find safe alternative drugs. Two patients developed reactions to high-dose acetaminophen but no reaction to nimesulide and tolmetin sodium. When statistically significant parameters were analyzed in a logistic regression model, the presence of multiple NSAIDs hypersensitivity in the patient history (odds ratio 26.6 [95% confidence interval, 1.47-481.63]; p = 0.026) and the emergence of a reaction within an hour (odds ratio 26.4 [95% confidence interval, 1.73-403.11]; p = 0.019) were found as the independent factors to predicted actual NSAID hypersensitivity. CONCLUSION: The emergence of a reaction within an hour of taking the drug and the presence of multiple NSAIDs hypersensitivity history increased the possibility of actual NSAID hypersensitivity. Nimesulide, low-dose acetaminophen, and tolmetin sodium could be used as safe alternative drugs in patients with multiple NSAIDs hypersensitivity. PMID- 26831850 TI - Difficulties encountered in the emergency department by patients with hereditary angioedema experiencing acute attacks. AB - BACKGROUND: Hereditary angioedema (HAE) is a rare, potentially life-threatening disease characterized by recurrent angioedema attacks. Abdominal symptoms of HAE typically mimic numerous abdominal emergencies, which may result in a delay of correct diagnosis and inappropriate treatments. OBJECTIVE: We aimed to evaluate the difficulties experienced by patients with HAE in Turkish emergency departments (ED). METHODS: We conducted face-to-face interviews with patients with HAE by using a questionnaire regarding the clinical and demographic data of the patients and difficulties encountered during ED admissions. RESULTS: The mean (standard deviation) age of 34 patients with HAE (25 women, 9 men) was 36.2 +/- 11.5 years and the mean (standard deviation) delay in diagnosis was 17.2 +/- 9.7 years. Inappropriate treatment for HAE attacks was administered to 88.2% (n = 30) of patients in the ED, despite their diagnosis of HAE. The most frequent difficulty was "not knowing how to administer C1 inhibitor concentrate" (n = 11 [32.4%]). Other difficulties encountered were as follows: ED staff being unaware of HAE (n = 6 [17.6%]), lack of C1 inhibitor concentrate in the ED (n = 3 [8.8%]), and kept waiting for the appropriate treatment in triage despite their having angioedema in the head-and-neck region (n = 2 [5.9%]). CONCLUSION: Patients with HAE encounter difficulties in the ED, and the delay in diagnosis could be due to a low level of awareness regarding HAE. Therefore, the management of HAE in EDs requires improvement. PMID- 26831849 TI - Lifetime prevalence of childhood eczema and the effect of indoor environmental factors: Analysis in Hispanic and non-Hispanic white children. AB - BACKGROUND: The prevalence of eczema varies markedly across the globe. It is unclear whether the geographic variation is due to race and/or ethnic differences, environmental exposures, or genetic factors. OBJECTIVE: We investigated the effects of ethnicity and environmental exposures on eczema in Hispanic white and non-Hispanic white children who participated in the Southern California Children's Health Study. METHODS: We performed a cross-sectional study with sociodemographic predictors and environmental exposures among Hispanic white and non-Hispanic white children ages 4-8 years enrolled in the Children's Health Study, 2002-2003. RESULTS: Eczema prevalence differed by ethnicity: Hispanic whites showed lower prevalence (13.8%) compared with non-Hispanic whites (20.2%), and adjustment for sociodemographic factors did not account for the ethnic difference (odds ratio [OR] 0.79 [95% confidence interval {CI}, 0.65-0.95]). Parental history of allergic disease had a larger effect in Hispanic whites than in non-Hispanic whites (p for interaction = 0.005). High maternal education level (OR 1.46 [95% CI, 1.14-1.87]), parental history of allergic disease (OR 2.21 [95% CI, 1.78-2.76]), and maternal smoking during pregnancy (OR 1.44 [95% CI, 1.06 1.95]) increased the risk of eczema. Indoor environmental factors (e.g., mold, water damage, humidifier use) increased the risk of eczema in non-Hispanic whites independent of a parental history of allergic disease, but, in Hispanic whites, increased risks were observed, primarily in children without a parental history of allergic disease. CONCLUSION: Hispanic white children in southern California had a lower prevalence of eczema than non-Hispanic whites, and this ethnic difference was not accounted for by sociodemographic differences. The effects of a parental history of allergic disease and indoor environmental exposures on eczema varied by ethnicity, which indicated that the etiology of eczema may differ in Hispanic whites and in non-Hispanic whites. PMID- 26831852 TI - For the Patient. PMID- 26831851 TI - A 73-year-old woman with persistent diarrhea and onychomycosis. AB - We present a case of a 73-year-old woman who presented with chronic watery diarrhea, weight loss, and frequent sinus and nail fungal infections. Her previous workup with a gastroenterologist failed to reveal any causative agent for her symptoms. She considered herself healthy until a thymic tumor was discovered and removed years ago. Subsequently, she developed multiple sinus infections refractory to treatment. Relevant immunology laboratory tests were conducted, which led to the diagnosis. This case illustrated the need for a detailed history and thorough immunologic assessment, and the requirement to maintain a broad differential diagnosis. PMID- 26831853 TI - Sexual Victimization and Subsequent Police Reporting by Gender Identity Among Lesbian, Gay, Bisexual, Transgender, and Queer Adults. AB - Prevalence of sexual victimization among lesbian, gay, bisexual, transgender, and queer (LGBTQ) persons is frequently found to be higher than the prevalence reported by their heterosexual peers. Transgender individuals are often included solely as part of larger LGBTQ research samples, potentially obfuscating differences between sexual orientation and gender identity. In this study, the authors examined sexual assault/rape in a large convenience sample of LGBTQ adults (N = 1,124) by respondents' gender identity (cisgender, transgender) to determine whether differences exist in lifetime prevalence of sexual assault/rape and subsequent police reporting. Findings indicate transgender individuals report having experienced sexual assault/rape more than twice as frequently as cisgender LGBQ individuals. Authors found no statistically significant difference in reporting sexual violence to police. Implications for research and practice are discussed. PMID- 26831854 TI - Fecal glucocorticoid metabolite responses to management stressors and social change in four species of callitrichine monkeys. AB - The use of enzyme immunoassays (EIA) for the non-invasive measurement of glucocorticoids provides a valuable tool for monitoring health and welfare in sensitive species. We validated methods for measuring fecal glucocorticoid metabolites (FGM) using the response to veterinary exams for four species of callitrichine monkeys: golden lion tamarin (Leontopithecus rosalia, n = 7), callimico (Callimico goeldii, n = 2), pied tamarin (Saguinus bicolor, n = 2), and white-fronted marmoset (Callithrix geoffroyi, n = 2). Routine veterinary exams were performed for the golden lion tamarins and callimicos, but exams for the pied tamarins and white-fronted marmosets were prompted by the death of a social partner. Prior to veterinary exams, fecal markers were evaluated to allow collection of individual samples and estimate approximate gut transit times. Based on this assessment, individual markers were fed in the afternoon, and fresh morning fecal samples were collected throughout this study. Following a veterinary exam, FGM increased roughly 3- to 28-fold above baseline in all species. Although FGM for most species returned to baseline concentrations within 24-48 h, the marmosets exhibited a progressive increase in FGM after an exam in response to the death of a breeding female and subsequent hand-rearing of a neonate. Individual differences were noted in the callimicos and tamarins, with higher baseline FGM levels in females vs. males, although small sample size precluded a clear determination of sex differences. To our knowledge, this is the first study to measure FGM in callimicos and white-fronted marmosets and the first to compare FGM across callitrichine species. These findings highlight the broad applicability of this EIA to measure the stress response of callitrichine monkeys. The progressive increase in FGM in the marmosets during hand-rearing of a neonate suggests that care should be taken to minimize this disturbance as much as possible. PMID- 26831855 TI - Long-term results of microfracture in the treatment of talus osteochondral lesions. AB - PURPOSE: Osteochondral lesions of the talus are common injuries, and many clinicians consider arthroscopic debridement and microfracture as the first-stage treatment. This study assessed the long-term clinical and radiographic outcomes of arthroscopic debridement and microfracture for osteochondral lesions of the talus. METHODS: A total of 82 patients (48 males, 34 females) who were treated with arthroscopic debridement and microfracture for osteochondral lesions of the talus between 1996 and 2009 with a minimum 5-year follow-up were included in our study group. Functional scores (AOFAS, VAS) and ankle range of motion were determined, and an arthrosis evaluation was performed. Subgroup evaluations based on age, lesion localization, and defect size were performed using functional outcome correlations. RESULTS: The mean age of the patients was 35.9 +/- 13.4 years (14-69 years), and the mean follow-up period was 121.3 months (61-217 months). The mean defect size was 1.7 +/- 0.7 cm2 (0.25-5). The mean pre operative AOFAS score was 58.7 +/- 5.2 (49-75), and the mean post-operative AOFAS score was 85.5 +/- 9.9 (56-100). At the last follow-up, 35 patients (42.6%) had no symptoms and 19 patients (23.1%) had pain after walking more than 2 h or after competitive sports activities. Radiological assessments of arthrosis revealed that no patient had grade 4 arthritis but that 27 patients (32.9%) had a one stage increase in their arthrosis level. Subgroup analyses of the lesion location demonstrated that lateral lesions had significantly better functional results (p = 0.02). CONCLUSIONS: Arthroscopic debridement and microfracture provide a good option for the treatment of osteochondral lesions of the talus over the long term in select patients. Functional outcomes do not correlate with defect size or patient age. Orthopaedic surgeons should adopt the microfracture technique, which is minimally invasive and effective for treating osteochondral lesions of the talus. LEVEL OF EVIDENCE: IV. PMID- 26831856 TI - Smoking increases the risk of early meniscus repair failure. AB - PURPOSE: The goal of this study is to determine whether patients who smoke cigarettes at the time of surgery are at significantly increased risk of early meniscus repair failure relative to non-smokers. METHODS: Retrospective chart review identified 64 current smokers within a series of 444 consecutive patients who underwent meniscus repair during a 7 years period. Fifty-two of these 64 smokers were available for follow-up and were matched by age, sex, and ACL status with non-smokers from the same cohort. Records of these 104 patients with a total of 120 meniscus repairs were reviewed to identify meniscus repair failure (defined as repeat surgery on the index meniscus) during the median 13-month (range: 3-79 months) follow-up period. RESULTS: The smoking and non-smoking groups were similar in age, sex, ACL status, BMI, meniscus repair technique, and meniscus involved. Meniscus repair failure occurred in 19 of the 112 menisci in 104 patients, for an overall failure risk of 17 %. Of the 19 failures, 14 occurred in 79 repaired medial menisci (18 % failure risk) and 5 occurred in 33 repaired lateral menisci (15 % failure risk). Meniscus repair failure occurred in significantly more smokers (15 failures in 56 menisci in 52 patients -27 % failure risk) than non-smokers (4 failures in 56 menisci in 52 patients -7 % failure risk) (p = 0.0076). CONCLUSIONS: Smoking is associated with significantly increased risk of early meniscus repair failure as defined by the incidence of repeat surgery on the index meniscus. LEVEL OF EVIDENCE: III. PMID- 26831857 TI - A randomized controlled clinical and radiological trial about outcomes of navigation-assisted TKA compared to conventional TKA: long-term follow-up. AB - PURPOSE: Well balanced knees with good alignment are essential for a well functioning TKA with long survival of its implants. This prospective randomized study comparing navigation-assisted TKA and conventional TKA reported the clinical and radiological outcomes at a follow-up of 9 years. The purpose of this study was to compare the clinical and radiological outcomes for patients who underwent navigation-assisted TKA or conventional TKA after long-term follow-up. METHODS: A total of 80 patients (88 knees) were available for physical and radiological examination 9 years after TKA. Clinical outcomes were evaluated using HSS, WOMAC, and KS function and pain scores. And radiological outcomes of the component loosening and its survivorship during 9-year follow-up were also evaluated. RESULTS: There were no significant differences in the field of clinical outcomes between the two groups. In terms of radiological outcomes, the navigation group had fewer alignment outliers (7.3 vs 20 %, p = 0.006). Although the clinical outcomes showed no differences between the two groups, the survival rate was slightly better in the navigation group than in the conventional group without statistical significance (best-case scenario 100 vs 95.3 %, n.s., worst case scenario 95.6 vs 88.4 %, n.s.). CONCLUSION: Navigation-assisted TKA produced better alignment outcomes and better survival rates than conventional instruments although some of the differences were not statistically significant. LEVEL OF EVIDENCE: I. PMID- 26831858 TI - Bone marrow concentrate and platelet-rich plasma differ in cell distribution and interleukin 1 receptor antagonist protein concentration. AB - PURPOSE: Bone marrow concentrate (BMC) and platelet-rich plasma (PRP) are used extensively in regenerative medicine. The aim of this study was to determine differences in the cellular composition and cytokine concentrations of BMC and PRP and to compare two commercial BMC systems in the same patient cohort. METHODS: Patients (29) undergoing orthopaedic surgery were enrolled. Bone marrow aspirate (BMA) was processed to generate BMC from two commercial systems (BMC-A and BMC-B). Blood was obtained to make PRP utilizing the same system as BMC-A. Bone marrow-derived samples were cultured to measure colony-forming units, and flow cytometry was performed to assess mesenchymal stem cell (MSC) markers. Cellular concentrations were assessed for all samples. Catabolic cytokines and growth factors important for cartilage repair were measured using multiplex ELISA. RESULTS: Colony-forming units were increased in both BMCs compared to BMA (p < 0.0001). Surface markers were consistent with MSCs. Platelet counts were not significantly different between BMC-A and PRP, but there were differences in leucocyte concentrations. TGF-beta1 and PDGF were not different between BMC-A and PRP. IL-1ra concentrations were greater (p = 0.0018) in BMC-A samples (13,432 pg/mL) than in PRP (588 pg/mL). The IL-1ra/IL-1beta ratio in all BMC samples was above the value reported to inhibit IL-1beta. CONCLUSIONS: The bioactive factors examined in this study have differing clinical effects on musculoskeletal tissue. Differences in the cellular and cytokine composition between PRP and BMC and between BMC systems should be taken into consideration by the clinician when choosing a biologic for therapeutic application. LEVEL OF EVIDENCE: Clinical, Level II. PMID- 26831859 TI - Prosthetic knee infection by resistant bacteria: the worst-case scenario. AB - PURPOSE: The aim of the present paper was to determine (1) the incidence of failure (defined as the persistence or the recurrence of the infection), (2) the incidence of prosthesis (or even limb) loss (defined as the final need for an arthrodesis, resection arthroplasty or amputation) and (3) what factors could influence the failure in patients treated with a two-stage reimplantation for periprosthetic knee infections caused by resistant bacteria. METHODS: The authors retrospectively reviewed 29 total knee arthroplasties infected by resistant bacteria in 29 patients who underwent a two-stage revision. Between the stages, intravenous-targeted antibiotics were administered for a median period of 8 (range 6-12) weeks. Median follow-up was 10 (range 7-14) years. RESULTS: The authors found that failure occurred in 5 of 29 patients (17.2 %). When methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MR-CoNS) were involved, failure rate was 10 % (2 of 20). When vancomycin-resistant enterococcus (VRE), multidrug-resistant (MDR) Acinetobacter baumannii and MDR Pseudomonas aeruginosa were involved, the failure rate was 33.3 % (3 of 9). Of those five patients, two underwent amputations, one chronic suppressive antibiotic therapy, one arthrodesis and one resection arthroplasty; among them, three lost the limb (10.3 % of the overall group). Timing of reimplantation and patient comorbidities did not significantly influence the failure. CONCLUSIONS: Two-stage protocol resulted in a viable option for patients with infections by some resistant organisms (MRSA and MR CoNS). However, when highly resistant organisms were involved (VRE, MDR Acinetobacter Baumannii and MDR Pseudomonas aeruginosa), the failure rate was much higher. In all cases of failure of the two-stage reimplantation, prosthesis (or even limb) loss occurred. Consequently, patients should be counselled that when highly resistant bacteria are involved, two-stage reimplantation could not be successful, with high final risk of prosthesis (or even limb) loss. LEVEL OF EVIDENCE: Retrospective case series, Level IV. PMID- 26831860 TI - Facing the decision about the treatment of hip or knee osteoarthritis: What are patients' needs? AB - PURPOSE: There is an increasing interest in modern orthopaedic practice to empower patients to participate in shared decision-making. Decision aids are thought to be helpful in this process. Before creating decision aids for patients with osteoarthritis in the knee or hip, the goal was to identify the needs of patients and physicians when deciding about the treatment. Specifically, this study tested the null hypothesis that there is no significant difference in decisional conflict between patients with knee or hip osteoarthritis and orthopaedic surgeons. METHODS: Thirty-three orthopaedic surgeons and 172 patients with either knee or hip osteoarthritis were surveyed. Patients entered their demographic information and completed the Knee Injury and Osteoarthritis Outcome Score/Hip Disability and Osteoarthritis Outcome Score, the Assessment of Needs survey based on the Ottawa Decision Support Framework, the Decisional Conflict Scale, the Pain Self-Efficacy Questionnaire, the Patient-Doctor Relationship Questionnaire-9, the Pain Anxiety Symptoms Scale and the Patient Health Questionnaire. Physicians entered their demographic and professional information and completed the Assessment of Needs survey based on the Ottawa Decision Support Framework and the Decisional Conflict Scale. RESULTS: The results showed that there was a significant difference (P < 0.01) between patients [mean (SD), 33 (19)] and physicians [mean (SD), 24 (14)], regarding decisional conflict about the treatment of knee and hip osteoarthritis. It also showed that patients' decisional conflict was associated with the patient-doctor relationship, and there was a need for information and clearness of one's values for risks and benefits. CONCLUSION: Patients had a higher magnitude of decisional conflict than physicians and that the level of decisional conflict was positively influenced by the patient-doctor relationship. Patients had high needs regarding information and clearness of one's values for risks and benefits. LEVEL OF EVIDENCE: II. PMID- 26831861 TI - Extent of vertical cementing as a predictive factor for radiolucency in revision total knee arthroplasty. AB - PURPOSE: Limited information is available regarding the effects of cementing extent on implant stability in patients who have undergone revision total knee arthroplasty (TKA). As such, the goals of this study were: (1) to determine the correlation between the extent of vertical cementing and implant loosening; (2) to determine whether the extent of cementing is a potential predictive factor for radiolucency; and (3) to evaluate the minimal amount of cement needed for a stable implant during revision TKA using a hybrid technique. METHODS: One hundred nine stemmed/revision TKAs with a mean follow-up period of 5 years were retrospectively analysed. In each case, a single varus-valgus constrained implant was used and fixed with a hybrid technique. Implant stability was evaluated according to the modified Knee Society radiographic scoring system. The extent of vertical cementing was defined as the longitudinal length from the implant base to the end of the radiopaque line around the stem on radiograph. Its correlation with implant stability was analysed, and the minimal value for a stable implant was evaluated with a receiver operating characteristic (ROC) analysis. RESULTS: The mean extent of vertical cementing was longer in stable implants (femur: p = 0.001, tibia: p = 0.004) and significantly correlated with implant stability (femur: p < 0.001, tibia: p = 0.001). A logistic regression analysis revealed that the risk of loosening was 8.7-16.1 times higher when the extent of cementing was <40 mm, which was located at the stem-implant junction of the modular implant. The minimal extent of vertical cementing was estimated to be 60 mm for a stable femoral implant and 50 mm for a tibial implant. CONCLUSIONS: The hybrid fixation technique with a cementing extent >60 mm for the femur and 50 mm for the tibia was durable at a mean follow-up period of 5 years. Vertical cementing 10-20 mm above the stem-implant junction is recommended when performing revision TKA using this technique. LEVEL OF EVIDENCE: IV. PMID- 26831862 TI - Web-based survey results: surgeon practice patterns in Italy regarding anterior cruciate ligament reconstruction and rehabilitation. AB - PURPOSE: The aim of this study was to report Italian orthopaedic surgeons' management of choice for ACL reconstruction and rehabilitation, and to compare surgical applications and rehabilitation approaches of Italian surgeons to the current approaches of "ACL Study Group". A secondary purpose was to compare the preferences of subgroup based on graft choice, surgical techniques and experience. METHODS: A web-based survey was developed to investigate the attitudes of members of a national association specialized in sports traumatology and knee surgery (SIGASCOT) regarding surgical techniques, routine post-operative applications, rehabilitation approaches and starting time of specific activities and exercises following ACL reconstruction. RESULTS: The response rate was 17 % (131 questionnaires). The most popular graft type was hamstring tendon (81 % in male patients, and 91 % in female patients). The rate of continuous passive motion use was 55 %. Half surgeons routinely used a brace (49 %), usually a hinged brace. In total, 33.0 % of surgeons allowed patients to load the operated knee as much as tolerated within the first 2 weeks. Fifty-nine per cent of surgeons did not limit full flexion within the first 2 weeks. Most surgeons advise to wait until 4 months or more (97 %) for return to sports not requiring contact, and 6 months or more for full-contact sport (86 %). CONCLUSIONS: This survey demonstrates clear trends in the practice of ACL reconstruction and rehabilitation in Italy. The data obtained from the SIGASCOT members revealed a more conservative approach when compared to the current approaches of "ACL Study Group". LEVEL OF EVIDENCE: Cross-sectional survey, Level III. PMID- 26831863 TI - The relationship between constitutional alignment and varus osteoarthritis of the knee. AB - PURPOSE: The role of neutral alignment in total knee arthroplasty (TKA) on short- and long-term outcomes has become controversial. Based on the concept of constitutional varus, it has been suggested that under-correction in TKA in a varus osteoarthritis (OA) population might lead to better clinical outcomes. However, it is still unknown what the relationship between constitutional varus and the development of end-stage OA is. The goal of this study was to analyse the contribution of constitutional varus in a medial OA population and to define a correlation between the constitutional alignment and end-stage varus OA. METHODS: Based on full-length radiographs, corrected for the intra-articular deformity of the knee, of 315 patients with unilateral end-stage medial OA of the knee (Charnley type A), a correlation in the coronal plane was made between medial end stage OA and the contralateral non-arthritic side. RESULTS: With increasing varus alignment in the arthritic limb, the physiologic limb alignment also became more varus. The proportion of constitutional varus rose with increasing overall alignment and was found to be continuous for males. Constitutional varus was three times higher in men when the overall arthritic alignment was greater more than 6 degrees varus. CONCLUSION: Constitutional varus significantly contributes to varus osteoarthritis and was found to be higher than in the general population. LEVEL OF EVIDENCE: III. PMID- 26831864 TI - Enhancing the Yield of Active Recombinant Chitobiase by Physico-Chemical and In Vitro Refolding Studies. AB - Chitobiase (CHB) is an important enzyme for the production of N-acetyl-D glucosamine from the chitin biopolymer in the series of chitinolytic enzymes. Majority of over-expressed CHB (58%) in E. coli expression system led to formation of inclusion bodies. The production and soluble yield of active CHB was enhanced by co-expression with GroEL/ES chaperonin, optimizing culture conditions and solubilization followed by refolding of remaining inactive chitobiase present in the form of inclusion bodies. The growth of recombinant E. coli produced 42% CHB in soluble form and the rest (~58%) as inclusion bodies. The percentage of active CHB was enhanced to 71% by co-expression with GroEL/ES chaperonin system and optimizing culture conditions (37 degrees C, 200 rpm, IPTG--0.5 mM, L arabinose--13.2 mM). Of the remaining inactive CHB present in inclusion bodies, 37% could be recovered in active form using pulsatile dilution method involving denaturants (2 M urea, pH 12.5) and protein refolding studies (1.0 M L-arginine, 5% glycerol). Using combinatorial approach, 80% of the total CHB expressed, could be recovered from cells grown in one litre of LB medium is a step forward in replacing hazardous chemical technology by biotechnological process for the production of NAG from chitinous waste. PMID- 26831866 TI - Investigation of the Effects of Extracellular Osmotic Pressure on Morphology and Mechanical Properties of Individual Chondrocyte. AB - It has been demonstrated that most cells of the body respond to osmotic pressure in a systematic manner. The disruption of the collagen network in the early stages of osteoarthritis causes an increase in water content of cartilage which leads to a reduction of pericellular osmolality in chondrocytes distributed within the extracellular environment. It is therefore arguable that an insight into the mechanical properties of chondrocytes under varying osmotic pressure would provide a better understanding of chondrocyte mechanotransduction and potentially contribute to knowledge on cartilage degeneration. In this present study, the chondrocyte cells were exposed to solutions with different osmolality. Changes in their dimensions and mechanical properties were measured over time. Atomic force microscopy (AFM) was used to apply load at various strain-rates and the force-time curves were logged. The thin-layer elastic model was used to extract the elastic stiffness of chondrocytes at different strain-rates and at different solution osmolality. In addition, the porohyperelastic (PHE) model was used to investigate the strain-rate-dependent responses under the loading and osmotic pressure conditions. The results revealed that the hypo-osmotic external environment increased chondrocyte dimensions and reduced Young's modulus of the cells at all strain-rates tested. In contrast, the hyper-osmotic external environment reduced dimensions and increased Young's modulus. Moreover, using the PHE model coupled with inverse FEA simulation, we established that the hydraulic permeability of chondrocytes increased with decreasing extracellular osmolality which is consistent with previous work in the literature. This could be due to a higher intracellular fluid volume fraction with lower osmolality. PMID- 26831865 TI - Suspended particles only marginally reduce pyrethroid toxicity to the freshwater invertebrate Gammarus pulex (L.) during pulse exposure. AB - Current ecotoxicological research on particle-associated pyrethroids in freshwater systems focuses almost exclusively on sediment-exposure scenarios and sediment-dwelling macroinvertebrates. We studied how suspended particles influence acute effects of lambda-cyhalothrin and bifenthrin on the epibenthic freshwater amphipod Gammarus pulex (L.) using brief pulse exposures followed by a 144 h post exposure recovery phase. Humic acid (HA) and the clay mineral montmorillonite (MM) were used as model sorbents in environmentally realistic concentrations (5, 25 and 125 mg L(-1)). Mortality of G. pulex was recorded during the post exposure recovery phase and locomotor behavior was measured during exposure to lambda-cyhalothrin. We found that HA in concentrations >=25 mg L(-1) adsorbed the majority of pyrethroids but only reduced mortality of G. pulex up to a factor of four compared to pyrethroid-only treatments. MM suspensions adsorbed a variable fraction of pyrethroids (10% for bifenthrin and 70% for lambda-cyhalothrin) but did not significantly change the concentration-response relationship compared to pure pyrethroid treatments. Behavioral responses and immobilisation rate of G. pulex were reduced in the presence of HA, whereas behavioral responses and immobilisation rate were increased in the presence of MM. This indicates that G. pulex was capable of sensing the bioavailable fraction of lambda-cyhalothrin. Our results imply that suspended particles reduce to only a limited extent the toxicity of pyrethroids to G. pulex and that passive uptake of pyrethroids can be significant even when pyrethroids are adsorbed to suspended particles. PMID- 26831867 TI - International consensus on ANA patterns (ICAP): the bumpy road towards a consensus on reporting ANA results. AB - The International Consensus on ANA Patterns (ICAP) was initiated as a workshop aiming to thoroughly discuss and achieve consensus regarding the morphological patterns observed in the indirect immunofluorescence assay on HEp-2 cells. One of the topics discussed at the second ICAP workshop, and addressed in this paper, was the harmonization of reporting ANA test results. This discussion centered on the issue if cytoplasmic and mitotic patterns should be reported as positive or negative. This report outlines the issues that impact on two major different reporting methods. Although it was appreciated by all participants that cytoplasmic and mitotic patterns are clinically relevant, implications for existing diagnostic/classification criteria for ANA-associated diseases in particular hampered a final consensus on this topic. Evidently, a more concerted action of all relevant stakeholders is required. Future ICAP workshops may help to facilitate this action. PMID- 26831868 TI - Simultaneous detection of celiac disease-specific IgA antibodies and total IgA. AB - PURPOSE: Celiac disease (CD) serology requires analysis of tissue transglutaminase type-2 (TG2autoAbs), deamidated gliadin (DGAbs), and as reference endomysial autoantibodies (EmA). Total IgA assessment helps to determine IgA-deficient CD patients. The novel multiplex indirect immunofluorescence (IIF) technique CytoBead was used to develop the first quantitative one-step serological CD assay comprising both simultaneous IgA autoAb and total IgA testing. METHODS: CytoBead CeliAK detecting TG2autoAb, DGAb, EmA, and simultaneously total IgA uses fluorescent microparticles for antigen and antibody immobilization along with monkey-esophagus tissue sections on glass slides. The assay was interpreted visually by classical fluorescent microscopy and digital IIF using AKLIDES((r)). Overall, 380 samples (155 CD patients, 5 with IgA deficiency, 68 with cystic fibrosis, 59 with eye disease, 93 blood donors) were run for performance analysis. Data were compared with classical IgA autoAb analysis by ELISA and IIF. RESULTS: Comparing CD-specific IgA autoAb testing by CytoBead with classical IIF and ELISA, very good agreements for EmA, TG2autoAb, and DGAb were determined (Cohen's kappa = 0.98, 0.96, 0.85, respectively). The difference between multiplex and single testing revealed a significant difference for TG2autoAb testing only (McNemar, p = 0.0078). Four CD patients and 4 controls demonstrated TG2autoAb positivity by ELISA but were negative by CytoBead. Further, 140/155 (90.9 %) CD patients demonstrated TG2autoAb levels above ten times the upper normal and all five IgA-deficient samples IgA levels <0.2 g/L by CytoBead. CONCLUSIONS: The novel multiplex CytoBead CeliAK enables simultaneous CD-specific autoAb and IgA deficiency analyses comparable with classical testing by single-parameter assays. Thus, comprehensive CD serology by CytoBead can alleviate the workload in routine laboratories. PMID- 26831869 TI - Time courses and variability of pyrethroid biomarkers of exposure in a group of agricultural workers in Quebec, Canada. AB - PURPOSE: Cypermethrin is a pyrethroid pesticide widely used in agriculture. Exposure can be assessed through biomonitoring. However, interpretation of results requires a proper knowledge of the toxicokinetics of the exposure biomarkers of interest. This study aimed at characterizing typical urinary time courses of biomarkers of exposure to cypermethrin in farm workers in Quebec following an exposure episode, distribution of values and variability, and predictors of elevated excretion levels. METHODS: Workers provided total voids before seasonal spraying and during three consecutive days following an exposure period. Personal factors, professional tasks, and exposure conditions were documented by questionnaire. The urinary metabolites cis- and trans-3-(2,2 dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acids (DCCA) and 3 phenoxybenzoic acid (3-PBA) were quantified. RESULTS: Time courses showed significant variations of metabolite levels through time, although a clear profile typical of an acute exposure episode was not observed for several workers. However, maximum urinary levels in most exposed workers were generally reached 18-32 h following the onset of an exposure episode. Group comparison showed that applicators had higher excretions than workers performing inspection, harvest, or weeding. CONCLUSIONS: Time-dependent variations in excretions indicate the importance of serial urinary collections for a proper interpretation of a worker exposure pattern. In the context of group comparison, the alternative based on observed time courses and peak levels in most exposed workers would be the collection of urine samples prior to an exposure episode, at the end-of-shift after exposure onset and following morning void. When spot samples can only be collected for population exposure assessment, Monte Carlo simulations showed that iterative random selection of single urinary values from individual time courses observed in this study to predict distribution of values in the group of workers converged to similar central tendencies. PMID- 26831870 TI - Violence at work: forensic medical examination of police officers assaulted while on duty: comparisons with other groups of workers in two centres of the Paris area, 2010-2012. AB - PURPOSE: To test for differences in somatic, psychic and functioning outcomes associated with assaults across four groups of workers, of which three are structurally at high risk of occupational violence. To report and compare job characteristics, characteristics of the assault and medical findings in police officers and other workers at the time of a forensic examination performed shortly after they complained for being assaulted while working. METHODS: A two centre prospective study recruiting adult survivors of workplace violence who lodged a complaint to the judicial authorities and were examined by forensic physicians in the Paris area, between 2010 and 2012 over a 27-month period, was conducted. Victims were administered a dedicated questionnaire and filled in the peritraumatic dissociative experiences questionnaire. Bivariate and multivariate analyses were performed on collected data to account for potential biases. RESULTS: Compared to employees of public transports services, private security guards and other workers, police officers were less likely to report psychic disturbances and peritraumatic dissociative experiences, despite adverse factors such as a worse external working climate or more frequent exposure to workplace assaults. No differences were observed in terms of somatic symptoms or functional impairment across groups. CONCLUSIONS: Although structurally more exposed to adverse factors than other workers, police officers appeared to be more protected from negative outcomes. The reasons for this resilience should be more precisely investigated.